PMID- 25969379
TI  - A comparison of positive and negative reinforcement for compliance to treat
      problem behavior maintained by escape.
AB  - Previous research has shown that problem behavior maintained by escape can be
      treated using positive reinforcement. In the current study, we directly compared
      functional (escape) and nonfunctional (edible) reinforcers in the treatment of
      escape-maintained problem behavior for 5 subjects. In the first treatment,
      compliance produced a break from instructions. In the second treatment,
      compliance produced a small edible item. Neither treatment included escape
      extinction. Results suggested that the delivery of a positive reinforcer for
      compliance was effective for treating escape-maintained problem behavior for all
      5 subjects, and the delivery of escape for compliance was ineffective for 3 of
      the 5 subjects. Implications and future directions related to the use of positive
      reinforcers in the treatment of escape behavior are discussed. 

PMID- 25969380
TI  - Factors affecting the academic performance of optometry students in Mozambique.
AB  - PURPOSE: The Mozambique Eyecare Project is a higher education partnership for the
      development, implementation, and evaluation of a model of optometry training at
      UniLurio in Mozambique. There are many composite elements to the development of
      sustainable eye health structures, and appropriate education for eye health
      workers remains a key determinant of successful eye care development. However,
      from the first intake of 16 students, only 9 students graduated from the program,
      whereas only 6 graduated from the second intake of 24 students. This low
      graduation rate is attributable to a combination of substandard academic
      performance and student dropout. The aim of this article was to identify factors
      affecting the academic performance of optometry students in Mozambique. METHODS:
      Nine lecturers (the entire faculty) and 15 students (9 from the first intake and
      6 from the second) were recruited to the study. Clinical competency assessments
      were carried out on the students, semistructured individual interviews were
      conducted with the course lecturers, and a course evaluation questionnaire was
      completed by students. The results were combined to understand the complexities
      surrounding the optometry student training and performance. RESULTS: One student
      out of nine from the first intake and three students out of six from the second
      were graded as competent in all the elements of the refraction clinical
      competency examination. Analysis of data from the interviews and questionnaire
      yielded four dominant themes that were viewed as important determinants of
      student refraction competencies: student learning context, teaching context,
      clinic conditions and assessment, and the existing operating health care context.
      CONCLUSIONS: The evaluations have helped the university and course partners to
      better structure the teaching and adapt the learning environments by recommending
      a preparatory year and a review of the curriculum and clinic structure,
      implementing more transparent entry requirements, increasing awareness of the
      program, and improving Internet infrastructure.

PMID- 25969381
TI  - Ocular juvenile xanthogranuloma.
AB  - PURPOSE: To report the clinical and histopathologic characteristics and prognoses
      of three ocular juvenile xanthogranuloma (JXG) cases. CASE REPORTS: Three cases
      were included in this study. The first case involved a 5-year-old girl with an
      enlarging yellowish mass at the limbus with corneal involvement. Ultrasound
      biomicroscopy showed a poorly demarcated mass involving the underlying cornea and
      sclera. The mass was excised in combination with a lamellar keratoplasty
      procedure. No recurrence was seen at the 2-year follow-up. The second case
      involved a 2-year-old boy with an enlarging yellowish mass on the conjunctiva,
      without limbal involvement. The mass was excised with no recurrence noted 1 year
      later. The third case involved a 7-month-old girl with unilateral eye redness and
      photophobia combined with multiple orange-red, raised nodular lesions on the
      skin. Examination under general anesthesia revealed a gray-yellow mass in the
      inferior and temporal iridocorneal angles. The intraocular pressure and corneal
      diameter were normal. Examination using ultrasound biomicroscopy showed a high
      level echo lump in the inferior and temporal angles. There was no treatment for
      this case. At the 1-year follow up, the eye symptoms had resolved and the skin
      lesions were flat. Histopathologic examinations were completed on all three
      cases. The presence of Touton giant cells in hematoxylin-eosin staining, positive
      CD68 staining, and negative S-100 and CD1a staining confirmed the diagnosis of
      JXG. CONCLUSIONS: We report three histopathologically confirmed ocular JXG cases
      involving the corneoscleral limbus, conjunctiva, and iris with angle involvement,
      respectively. Ultrasound biomicroscopy performed on two cases demonstrated no
      obvious division between the mass and the surrounding structures. The cases with
      ocular surface involvement were successfully treated by excision and the case
      with iris involvement spontaneously regressed without any treatment. Early
      excision may be the better choice for ocular surface lesions, especially when
      corneal involvement is a possibility.

PMID- 25969382
TI  - Unreamed Intramedullary Nailing is a better alternative than External Fixator for
      Gustilo grade IIIB Tibial Fractures based on a meta-analysis.
AB  - BACKGROUND AND AIMS: There remains a controversy between unreamed intramedullary
      nailing and external fixation to treat Gustilo grade IIIB tibial fractures. To
      evaluate the comparative effectiveness and safeness of both methods for this type
      of fracture, we performed this meta-analysis. MATERIALS AND METHODS: Relevant
      original studies were searched in MEDLINE, EMBASE, China National Knowledge
      Infrastructure, and Cochrane Central Database (all through February 2014).
      Studies included in this meta-analysis had to compare the effectiveness or
      complications and provided sufficient data of interest. The patients treated by
      both methods were similar statistically in demography and injury mechanism. The
      Stata 11.0 was used to analyze all data. RESULTS: Six studies involving 163
      participants were included. Unreamed intramedullary nailing was associated with
      reduced time to union (standardized mean difference, -1.14; 95% confidence
      interval, -2.04 to -0.24) and lower rates of superficial infection (odds ratio:
      0.39; 95% confidence interval: 0.17-0.87) and malunion (odds ratio: 0.27; 95%
      confidence interval: 0.09-0.78). However, there were no significant differences
      in other adverse events including delayed union, non-union, deep infection, and
      fixation failure. CONCLUSION: The existing evidence supports unreamed
      intramedullary nailing to be a better method for treating Gustilo grade IIIB
      tibial fractures, and this might aid in the management of this sever injury.

PMID- 25969383
TI  - Outcomes of Male Sling Mesh Kit Placement in Patients with Neuropathic Stress
      Urinary Incontinence: A Single Institution Experience.
AB  - BACKGROUND AND OBJECTIVES: The mainstay of therapy in patients with neuropathic
      stress urinary incontinence (nSUI) has been through the use of artificial urinary
      sphincter (AUS). AUS infection/erosion rates are higher in nSUI patients and
      these patients tend to be younger, increasing the likelihood of multiple AUS
      revisions in the future. We review our experience with mesh male slings for
      patients with nSUI. METHODS: A retrospective review of patients who had mesh
      sling placement. RESULTS: Twenty patients were identified between 2003 and 2011.
      14/20 (70%) (5 = AdVance, 8 = InVance, 1 = Virtue) were available for long-term
      evaluation; in 6/20 (30%) the sling was removed for either infection or perineal
      wound breakdown. The mean time from injury to male sling was 148.2 (29-449)
      months. Pre-/post-op fluorourodynamic study was performed in 13 and 7 patients,
      respectively. There were no significant differences in ALPP (46.4 vs. 55.7 cm
      H2O, p = 0.106) and MCC (456.6 vs. 608 ml, p = 0.21) in the 7 patients who had a
      post-op study: five patients had new onset low bladder compliance and two had new
      onset detrusor overactivity post-sling. With a mean follow-up of 24.7 (1-66)
      months, 4/14 (28.6%) had no UI. CONCLUSIONS: With short-term follow-up, mesh male
      slings are a feasible option to treat nSUI. There appears to be a lower success
      rate for UI resolution, which may be attributable to new onset detrusor failure
      or wound infection requiring sling removal.

PMID- 25969384
TI  - Nocardiopsis mangrovei sp. nov., isolated from mangrove sediment.
AB  - Two Gram-positive actinobacterial strains, designated HA11166(T) and HA12420,
      were isolated from mangrove sediments in Hainan, China. The bacterial cells grew
      with 0-9 % (w/v) NaCl, at 15-40  degrees C and pH 5.0-10.0, with the optimum
      growth at 1 % NaCl, 30-37  degrees C and pH 7.0. The organisms had a range of
      chemical and morphological properties consistent with their classification in the
      genus Nocardiopsis. Phylogenetic analysis of the 16S rRNA gene sequences
      indicated that strains HA11166(T) and HA12420 can be affiliated to the genus
      Nocardiopsis and most closely related to Nocardiopsis trehalosi VKM Ac-942(T)
      (with the similarity of 97.2 and 97.5 %, respectively). The value of DNA-DNA
      relatedness between type strain HA11166(T), selected as the representative
      strain, and N. trehalosi VKM Ac-942(T) was 38.8 %. The DNA G+C content of strain
      HA11166(T) was 73.7 %. On the basis of these phenotypic and genotypic data,
      strains HA11166(T) and HA12420 are proposed to represent a novel species of the
      genus Nocardiopsis, for which the name Nocardiopsis mangrovei sp. nov. is
      proposed. The type strain is HA11166(T) (=CGMCC 4.7119(T)=DSM 46665(T)). 

PMID- 25969385
TI  - Evaluation of fluorimetric pH sensors for bioprocess monitoring at low pH.
AB  - Optical chemical sensors are the standard for pH monitoring in small-scale
      bioreactors such as microtiter plates, shaking flasks or other single-use
      bioreactors. The dynamic pH range of the so far commercially available
      fluorescent pH sensors applied in small-scale bioreactors is restricted to pH
      monitoring around neutral pH, although many fermentation processes are performed
      at pH < 6 on industrial scale. Thus, two new prototype acidic fluorescence pH
      sensors immobilized in single-use stirred-tank bioreactors, one with excitation
      at 470 nm and emission at 550 nm (sensor 470/550) and the other with excitation
      at 505 nm and emission at 600 nm (sensor 505/600), were characterized with
      respect to dynamic ranges and operational stability in representative
      fermentation media. Best resolution and dynamic range was observed with pH sensor
      505/600 in mineral medium (dynamic range of 3.9 < pH < 7.2). Applying the same pH
      sensors to complex medium results in a drastic reduction of resolution and
      dynamic ranges. Yeast extract in complex medium was found to cause background
      fluorescence at the sensors' operating wavelength combinations. Optical isolation
      of the sensor by adding a black colored polymer layer above the sensor spot and
      fixing an aperture made of adhesive photoresistant foil between the fluorescence
      reader and the transparent bottom of the polystyrene reactors enabled full re
      establishment of the sensor's characteristics. Reliability and operational
      stability of sensor 505/600 was shown by online pH monitoring (4.5 < pH < 5.8) of
      parallel anaerobic batch fermentations of Clostridium acetobutylicum for the
      production of acetone, butanol and ethanol (ABE) with offline pH measurements
      with a standard glass electrode as reference. 

PMID- 25969386
TI  - Enhancement of epsilon-poly-lysine production in epsilon-poly-lysine-tolerant
      Streptomyces sp. by genome shuffling.
AB  - epsilon-Poly-L-lysine (epsilon-PL) has been widely used as food additive.
      However, the self-inhibition of epsilon-PL on cell growth limits the accumulation
      of epsilon-PL in the wild-type strain. Here, we screened epsilon-PL-tolerant
      strain of Streptomyces sp. with higher epsilon-PL productivity by genome
      shuffling and studied the mechanism for the improvement. The initial mutant
      library was constructed by diethyl sulfate mutagenesis. After four rounds of
      protoplast fusion, a shuffled strain F4-22 with 3.11 g/L epsilon-PL productivity
      in shake flask, 1.81-fold in comparison with that of parent strain, was obtained.
      The higher aspartokinase activity was induced in F4-22 whereas no obvious changes
      have been found in epsilon-PL synthetic and degrading enzymes which indicated
      that the upstream reregulation of the precursor lysine synthesis rather than
      lysine polymerization or epsilon-PL degradation in shuffled strain accounted for
      the higher productivity. The activities of key enzymes in the central metabolic
      pathway were also enhanced in F4-22 which resulted in increased vigor of the
      strain and in delayed strain lysis during fermentation. These improved properties
      of shuffled strain led to the success of combining general two-stage fermentation
      into one-stage one in 5-L bioreactor with 32.7 % more epsilon-PL production than
      that of parent strain. The strategy used in this study provided a novel strain
      breeding approach of producers which suffered from epsilon-PL-like self
      inhibition of the metabolites. 

PMID- 25969387
TI  - Derek Bendall (1930-2014).
AB  - Derek Bendall carried out pioneering work on photosynthetic electron transport,
      particularly on protein-protein interactions, cytochromes, and cyclic electron
      transport, as well as on other topics including the biochemistry of tea. He was a
      keen musician and a gifted gardener, a devoted family man, and a delightful
      colleague and friend. The bioenergetics community, especially those working on
      photosynthesis, will miss him sorely. 

PMID- 25969389
TI  - Perpendicular magnetisation from in-plane fields in nano-scaled antidot lattices.
AB  - Investigations of geometric frustrations in magnetic antidot lattices have led to
      the observation of interesting phenomena like spin-ice and magnetic monopoles. By
      using highly focused magneto-optical Kerr effect measurements and x-ray
      microscopy with magnetic contrast we deduce that geometrical frustration in these
      nanostructured thin film systems also leads to an out-of-plane magnetization from
      a purely in-plane applied magnetic field. For certain orientations of the antidot
      lattice, formation of perpendicular magnetic domains has been found with a size
      of several MUm that may be used for an in-plane/out-of-plane transducer. 

PMID- 25969388
TI  - Role of Phosphorylation Sites in Desensitization of u-Opioid Receptor.
AB  - Phosphorylation of residues in the C-terminal tail of the u-opioid receptor
      (MOPr) is thought to be a key step in desensitization and internalization.
      Phosphorylation of C-terminal S/T residues is required for internalization (Just
      et al., 2013), but its role in desensitization is unknown. This study examined
      the influence of C-terminal phosphorylation sites on rapid desensitization of
      MOPr. Wild-type MOPr, a 3S/T-A mutant (S363A, T370A, S375A) that maintains
      internalization, 6S/T-A (S363A, T370A, S375A, T376A, T379A, T383A) and 11S/T-A
      (all C-terminal S/T residues mutated) mutants not internalized by MOPr agonists
      were stably expressed in AtT20 cells. Perforated patch-clamp recordings of MOPr
      mediated activation of G-protein-activated inwardly rectifying potassium channel
      (Kir3.X) (GIRK) conductance by submaximal concentrations of Met(5)-enkephalin
      (ME) and somatostatin (SST; coupling to native SST receptor [SSTR]) were used to
      examine desensitization induced by exposure to ME and morphine for 5 minutes at
      37 degrees C. The rates of ME- and morphine-induced desensitization did not
      correlate with phosphorylation using phosphorylation site-specific antibodies. ME
      induced MOPr desensitization and resensitization did not differ from wild-type
      for 3S/T-A and 6S/T-A but was abolished in 11S/T-A. Morphine-induced
      desensitization was unaffected in all three mutants, as was heterologous
      desensitization of SSTR. Morphine-induced desensitization (but not ME) was
      reduced by protein kinase C inhibition in wild-type MOPr and abolished in the
      11S/T-A mutant, as was heterologous desensitization. These findings establish
      that MOPr desensitization can occur independently of S/T phosphorylation and
      internalization; however, C-terminal phosphorylation is necessary for some forms
      of desensitization because mutation of all C-terminal sites (11S/T-A) abolishes
      desensitization induced by ME. 

PMID- 25969390
TI  - A dangerous lack of pharmacology education in medical and nursing schools: A
      policy statement from the American College of Clinical Pharmacology.

PMID- 25969391
TI  - Stochastic spontaneous calcium release events trigger premature ventricular
      complexes by overcoming electrotonic load.
AB  - AIMS: Premature ventricular complexes (PVCs) due to spontaneous calcium (Ca)
      release (SCR) events at the cell level can precipitate ventricular arrhythmias.
      However, the mechanistic link between SCRs and PVC formation remains incompletely
      understood. The aim of this study was to investigate the conditions under which
      delayed afterdepolarizations resulting from stochastic subcellular SCR events can
      overcome electrotonic source-sink mismatch, leading to PVC initiation. METHODS
      AND RESULTS: A stochastic subcellular-scale mathematical model of SCR was
      incorporated in a realistic model of the rabbit ventricles and Purkinje system
      (PS). Elevated levels of diastolic sarcoplasmic reticulum Ca(2+) (CaSR) were
      imposed until triggered activity was observed, allowing us to compile statistics
      on probability, timing, and location of PVCs. At CaSR>= 1500 umol/L PVCs
      originated in the PS. When SCR was incapacitated in the PS, PVCs also emerged in
      the ventricles, but at a higher CaSR (>=1550 umol/L) and with longer waiting
      times. For each model configuration tested, the probability of PVC occurrence
      increased from 0 to 100% within a well-defined critical CaSR range; this
      transition was much more abrupt in organ-scale models (~50 umol/L CaSR range)
      than in the tissue strand (~100 umol/L) or single-cell (~450 umol/L) models.
      Among PVCs originating in the PS, ~68% were located near Purkinje-ventricular
      junctions (<1 mm). CONCLUSION: SCR events overcome source-sink mismatch to
      trigger PVCs at a critical CaSR threshold. Above this threshold, PVCs emerge due
      to increased probability and reduced variability in timing of SCR events, leading
      to significant diastolic depolarization. Sites of lower electronic load, such as
      the PS, are preferential locations for triggering.

PMID- 25969392
TI  - Context-specific interactions between Notch and ALK1 cannot explain ALK1
      associated arteriovenous malformations.
AB  - AIMS: Notch and activin receptor-like kinase 1 (ALK1) have been implicated in
      arterial specification, angiogenic tip/stalk cell differentiation, and
      development of arteriovenous malformations (AVMs), and ALK1 can cooperate with
      Notch to up-regulate expression of Notch target genes in cultured endothelial
      cells. These findings suggest that Notch and ALK1 might collaboratively program
      arterial identity and prevent AVMs. We therefore sought to investigate the
      interaction between Notch and Alk1 signalling in the developing vertebrate
      vasculature. METHODS AND RESULTS: We modulated Notch and Alk1 activities in
      zebrafish embryos and examined effects on Notch target gene expression and
      vascular morphology. Although Alk1 is not necessary for expression of Notch
      target genes in arterial endothelium, loss of Notch signalling unmasks a role for
      Alk1 in supporting hey2 and ephrinb2a expression in the dorsal aorta. In
      contrast, Notch and Alk1 play opposing roles in hey2 expression in cranial
      arteries and dll4 expression in all arterial endothelium, with Notch inducing and
      Alk1 repressing these genes. Although alk1 loss increases expression of dll4,
      AVMs in alk1 mutants could neither be phenocopied by Notch activation nor rescued
      by Dll4/Notch inhibition. CONCLUSION: Control of Notch targets in arterial
      endothelium is context-dependent, with gene-specific and region-specific
      requirements for Notch and Alk1. Alk1 is not required for arterial identity, and
      perturbations in Notch signalling cannot account for alk1 mutant-associated AVMs.
      These data suggest that AVMs associated with ALK1 mutation are not caused by
      defective arterial specification or altered Notch signalling.

PMID- 25969393
TI  - Chemokines as effector and target molecules in vascular biology.
AB  - Chemokines are key mediators of inflammation. In pathological tissues, the main
      roles of chemokines are to regulate leucocyte accumulation through the activation
      of oriented cell migration and the activation of limited programs of gene
      transcription. Through these activities, chemokines exert many crucial functions,
      including the regulation of angiogenesis. The 'chemokine system' is tightly
      regulated at several levels, such as the post-transcriptional processing of
      ligands, the regulation of the expression and function of the receptors and
      through the expression of molecules known as 'atypical chemokine receptors',
      proteins that function as chemokine scavenging and presenting molecules. Several
      experimental evidence obtained in vitro, in animal models and in human studies,
      has defined a crucial role of chemokines in cardiovascular diseases. An intense
      area of research is currently exploring the possibility to develop new effective
      therapeutic strategies through the identification of chemokine receptor
      antagonists. 

PMID- 25969394
TI  - Equilibrium binding behavior of magnesium to wall teichoic acid.
AB  - Peptidoglycan and teichoic acids are the major cell wall components of Gram
      positive bacteria that obtain and sequester metal ions required for biochemical
      processes. The delivery of metals to the cytoplasmic membrane is aided by anionic
      binding sites within the peptidoglycan and along the phosphodiester polymer of
      teichoic acid. The interaction with metals is a delicate balance between the need
      for attraction and ion diffusion to the membrane. Likewise, metal chelation from
      the extracellular fluid must initially have strong binding energetics that weaken
      within the cell wall to enable ion release. We employed atomic absorption and
      equilibrium dialysis to measure the metal binding capacity and metal binding
      affinity of wall teichoic acid and Mg2+. Data show that Mg2+ binds to WTA with a
      1:2Mg2+ to phosphate ratio with a binding capacity of 1.27 MUmol/mg. The affinity
      of Mg2+ to WTA was also found to be 41*10(3) M(-1) at low metal concentrations
      and 1.3*10(3) M(-1) at higher Mg2+ concentrations due to weakening electrostatic
      effects. These values are lower than the values describing Mg2+ interactions with
      peptidoglycan. However, the binding capacity of WTA is 4 times larger than
      peptidoglycan. External WTA initially binds metals with positive cooperativity,
      but metal binding switches to negative cooperativity, whereas interior WTA binds
      metals with only negative cooperativity. The relevance of this work is to
      describe changes in metal binding behavior depending on environment. When metals
      are sparse, chelation is strong to ensure survival yet the binding weakens when
      essential minerals are abundant.

PMID- 25969395
TI  - Association between red and processed meat consumption and chronic diseases: the
      confounding role of other dietary factors.
AB  - BACKGROUND/OBJECTIVES: High consumption of meat has been linked with the risk for
      obesity and chronic diseases. This could partly be explained by the association
      between meat and lower-quality diet. We studied whether high intake of red and
      processed meat was associated with lower-quality dietary habits, assessed against
      selected nutrients, other food groups and total diet. Moreover, we studied
      whether meat consumption was associated with obesity, after adjustment for all
      identified associations between meat and food consumption. SUBJECTS/METHODS: The
      nationally representative cross-sectional study population consisted of 2190
      Finnish men and 2530 women, aged 25-74 years. Food consumption over the previous
      12 months was assessed using a validated 131-item Food Frequency Questionnaire.
      Associations between nutrients, foods, a modified Baltic Sea Diet Score and meat
      consumption (quintile classification) were analysed using linear regression. The
      models were adjusted for age and energy intake and additionally for education,
      physical activity and smoking. RESULTS: High consumption of red and processed
      meat was inversely associated with fruits, whole grain and nuts, and positively
      with potatoes, oil and coffee in both sexes. Results separately for the two types
      of meat were essentially similar. In a linear regression analysis, high
      consumption of meat was positively associated with body mass index in both men
      and women, even when using a model adjusted for all foods with a significant
      association with meat consumption in both sexes identified in this study.
      CONCLUSIONS: The association between meat consumption and a lower-quality diet
      may complicate studies on meat and health.

PMID- 25969396
TI  - Fish consumption and all-cause mortality: a meta-analysis of cohort studies.
AB  - BACKGROUND/OBJECTIVES: Although fish consumption may have an influence on
      specific mortality of major chronic diseases, the relationship between fish
      consumption and all-cause mortality remains inconsistent. SUBJECTS/METHODS: We
      performed a systematic search of publications using PubMed and Web of science up
      to 31 December 2014. Summary relative risk (RR) for the highest versus lowest
      category of fish consumption on risk of all-cause mortality was calculated by
      using a random effects model. Potential nonlinear relation was tested by modeling
      fish intake using restricted cubic splines with three knots at fixed percentiles
      of the distribution. RESULTS: Twelve prospective cohort studies with 672,389
      participants and 57,641 deaths were included in this meta-analysis. Compared with
      the lowest category, the highest category of fish intake was associated with
      about a 6% significantly lower risk of all-cause mortality (RR=0.94, 95%
      confidence interval (CI): 0.90, 0.98; I(2)=39.1%, P=0.06). The dose-response
      analysis indicated a nonlinear relationship between fish consumption and all
      cause mortality. Compared with never consumers, consumption of 60 g of fish per
      day was associated with a 12% reduction (RR=0.88, 95% CI: 0.83, 0.93) in risk of
      total death. CONCLUSIONS: These results imply that fish consumption was
      associated with a reduced risk of all-cause mortality.

PMID- 25969397
TI  - Childhood malnutrition in households with contemporary siblings: a scenario from
      urban Bangladesh.
AB  - This study aimed to determine the effect of the presence of under-5 siblings (?
      1) in a household on childhood malnutrition in urban Bangladesh. During 2000 and
      2013, a total of 16,948 under-5 children were enrolled in the Diarrhoeal Disease
      Surveillance of icddr,b. Under-5 siblings were categorised as ? 1 and none except
      the child himself. In univariate analysis, the presence of siblings was
      associated with 1.13 (risk ratios=1.13; 95% CI:1.06-1.20) times higher risk of
      being stunted, 1.17 (1.09-1.25) times for wasted and 1.19 (1.13-1.26) times
      underweight compared with their peers who did not have siblings. In multivariate
      analysis, such associations remained significant for stunting (1.08; 1.01-1.15),
      wasting (1.12; 1.04-1.21) and underweight (1.13, 1.06-1.19) after controlling for
      possible confounders such as age of child, sex, parental education, maternal
      employment, family size, wealth quintile and time (year). The presence of under-5
      siblings increases the risk of malnutrition in children in urban Bangladesh.

PMID- 25969398
TI  - Discovering networks altered by potential threat ("anxiety") using quadratic
      discriminant analysis.
AB  - Researchers have only recently begun using functional neuroimaging to explore the
      human response to periods of sustained anxious anticipation, namely potential
      threat. Here, we investigated brain responses acquired with functional MRI during
      an instructed threat of shock paradigm used to create sustained periods of
      aversive anticipation. In this re-analysis of previously published data, we
      employed quadratic discriminant analysis to classify the multivariate pattern of
      whole-brain functional connectivity and to identify connectivity changes during
      periods of potential threat. Our method identifies clusters with altered
      connectivity on a voxelwise basis, thus eschewing the need to define regions a
      priori. Classifier generalization was evaluated by testing on data from
      participants not used during training. Robust classification between threat and
      safe contexts was possible, and inspection of "diagnostic features" revealed
      altered functional connectivity involving the intraparietal sulcus, task-negative
      regions, striatum, and anterior cingulate cortex. We anticipate that the proposed
      method will prove useful to experimenters wishing to identify large-scale
      functional networks that distinguish between experimental conditions or groups. 

PMID- 25969399
TI  - Testing a dual-systems model of adolescent brain development using resting-state
      connectivity analyses.
AB  - The current study aimed to test a dual-systems model of adolescent brain
      development by studying changes in intrinsic functional connectivity within and
      across networks typically associated with cognitive-control and affective
      motivational processes. To this end, resting-state and task-related fMRI data
      were collected of 269 participants (ages 8-25). Resting-state analyses focused on
      seeds derived from task-related neural activation in the same participants: the
      dorsal lateral prefrontal cortex (dlPFC) from a cognitive rule-learning paradigm
      and the nucleus accumbens (NAcc) from a reward-paradigm. Whole-brain seed-based
      resting-state analyses showed an age-related increase in dlPFC connectivity with
      the caudate and thalamus, and an age-related decrease in connectivity with the
      (pre)motor cortex. nAcc connectivity showed a strengthening of connectivity with
      the dorsal anterior cingulate cortex (ACC) and subcortical structures such as the
      hippocampus, and a specific age-related decrease in connectivity with the ventral
      medial PFC (vmPFC). Behavioral measures from both functional paradigms correlated
      with resting-state connectivity strength with their respective seed. That is, age
      related change in learning performance was mediated by connectivity between the
      dlPFC and thalamus, and age-related change in winning pleasure was mediated by
      connectivity between the nAcc and vmPFC. These patterns indicate (i)
      strengthening of connectivity between regions that support control and learning,
      (ii) more independent functioning of regions that support motor and control
      networks, and (iii) more independent functioning of regions that support
      motivation and valuation networks with age. These results are interpreted vis-a
      vis a dual-systems model of adolescent brain development.

PMID- 25969400
TI  - Efficient Semitransparent Perovskite Solar Cells with Graphene Electrodes.
AB  - Semitransparent perovskite solar cells are prepared by laminating graphene
      transparent electrodes on the top for the first time. The device performance is
      optimized by improving the conductivity of the graphene electrodes and the
      contact between the graphene and the perovskite active layers during the
      lamination process. The devices show high power conversion efficiencies when they
      are illuminated from both sides. 

PMID- 25969401
TI  - Measures of the aversive effects of drugs: A comparison of conditioned taste and
      place aversions.
AB  - The present experiments directly compared the ability of the conditioned taste
      and place aversion designs (CTA and CPA, respectively) to measure the aversive
      effects of lithium chloride (LiCl) in male Sprague-Dawley rats. In the CTA
      assessment (Experiment 1), rats were given one of two novel tastes paired with
      LiCl (0, 0.18, 0.32, 0.56 or 1mEq/kg) and the alternate novel taste paired with
      vehicle the next day. This was repeated three times, followed by a final two
      bottle test. In the CPA assessment (Experiment 2), rats were given LiCl at the
      same doses and placed on one side of an unbiased two-chambered apparatus,
      followed by vehicle injection and placement on the opposite side on alternating
      days. This was repeated three times followed by free access to both sides in an
      assessment of relative preference. LiCl induced robust, dose-dependent taste
      aversions with rats receiving 0.32mEq/kg or greater consuming a smaller
      percentage of the drug-paired taste than that of controls. LiCl did not induce
      place aversions at any dose with LiCl- and vehicle-treated subjects displaying
      comparable preferences for the drug-paired side. The basis for the differences of
      the two designs in indexing LiCl's aversive effects was discussed. 

PMID- 25969402
TI  - Structure of the O-polysaccharide of the lipopolysaccharide of Pseudomonas
      chlororaphis subsp. aureofaciens UCM B-306.
AB  - Structure of the O-specific polysaccharide from Pseudomonas chlororaphis subsp.
      aureofaciens UCM B-306 was elucidated by sugar analysis along with 1D and 2D (1)H
      and (13)C NMR spectroscopy. The polysaccharide is built up of trisaccharide
      repeats containing D-rhamnose, 2,4-diacetamido-2,4,6-trideoxy-D-glucose (D
      QuiNAc4NAc), and 2-acetamido-2-deoxy-D-galacturonic acid (D-GalNAcA), which is
      amidated in ~40% repeats. It was suggested that the O-polysaccharide has a
      blockwise structure, which can be presented as follows: -[->3)-alpha-D-Rhap-(1
      >4)-alpha-D-GalpNAcA-(1->3)-alpha-D-QuipNAc4NAc-(1-]n-> and -[->3)-alpha-D-Rhap
      (1->4)-alpha-D-GalpNAcAN-(1->3)-alpha-D-QuipNAc4NAc-(1-]m->, where GalNAcAN
      indicates 2-acetamido-2-deoxy-D-galacturonamide, n:m=~3:2.

PMID- 25969403
TI  - Cobalt(III)-Catalyzed Aryl and Alkenyl C-H Aminocarbonylation with Isocyanates
      and Acyl Azides.
AB  - Expedient C-H aminocarbonylations of unactivated (hetero)arenes and alkenes were
      accomplished with a cobalt(III) catalyst that shows high functional group
      tolerance. The C-H functionalization occurred with excellent chemo-, site-, and
      diastereoselectivity and enabled step-economical reactions with isocyanates or
      acyl azides.

PMID- 25969408
TI  - Gene expression: Converging pathways.

PMID- 25969409
TI  - Visualization of energy: light dose indicator based on electrochromic gyroid nano
      materials.
AB  - The typical applications of electrochromic devices do not make use of the charge
      dependent, gradual optical response due to their slow voltage-sensitive
      coloration. However, in this paper we present a design for a reusable, self
      powered light dose indicator consisting of a solar cell and a gyroid-structured
      nickel oxide (NiO) electrochromic display that measures the cumulative charge per
      se, making use of the efficient voltage-sensitive coloration of gyroid materials.
      To circumvent the stability issues associated with the standard aqueous
      electrolyte that is typically accompanied by water splitting and gas evolution,
      we investigate a novel nano-gyroid NiO electrochromic device based on organic
      solvents of 1,1,1,3,3,3-hexafluoropropan-2-ol, and room temperature ionic liquid
      (RTIL) triethylsulfonium bis(trifluoromethylsulfonyl) imide ([SET3][TFSI])
      containing lithium bis(trifluoromethylsulfonyl) imide. We show that an effective
      light dose indicator can be enabled by nano-gyroid NiO with RTIL; this proves to
      be a reliable device since it does not involve solvent degradation or gas
      generation. 

PMID- 25969410
TI  - The Role of Integrated Knowledge Translation in Intervention Research.
AB  - There is widespread recognition across the full range of applied research
      disciplines, including health and social services, about the challenges of
      integrating scientifically derived research evidence into policy and/or practice
      decisions. These "disconnects" or "knowledge-practice gaps" between research
      production and use have spawned a new research field, most commonly known as
      either "implementation science" or "knowledge translation." The present paper
      will review key concepts in this area, with a particular focus on "integrated
      knowledge translation" (IKT)-which focuses on researcher-knowledge user
      partnership-in the area of mental health and prevention of violence against women
      and children using case examples from completed and ongoing work. A key
      distinction is made between the practice of KT (disseminating, communicating,
      etc.), and the science of KT, i.e., research regarding effective KT approaches.
      We conclude with a discussion of the relevance of IKT for mental health
      intervention research with children and adolescents.

PMID- 25969411
TI  - Wearable technology: using Google Glass as a teaching tool.
AB  - Wearable technology holds great promise in revolutionising healthcare delivery.
      The benefits can also be seen in medical education and delivering healthcare in
      remote places. We report the use of Google Glass technology as a teaching tool in
      broadcasting a procedure onto a mobile phone as a viewer, replacing expensive and
      often cumbersome existing equipment. 

PMID- 25969412
TI  - The effect of flexor digitorum profundus tendon shortening on jersey finger
      surgical repair: a cadaveric biomechanical study.
AB  - Delayed diagnosis of jersey finger injuries often results in retraction of the
      flexor digitorum profundus tendon. Current practice recommends limiting tendon
      advancement to 1 cm in delayed repairs. The purpose of this study was to
      investigate the biomechanical consequences of tendon shortening on the force
      required to form a fist. The flexor digitorum profundus muscle was isolated in
      ten cadaveric forearms and the force required to form a fist was recorded.
      Simulated jersey finger injuries to the ring finger were then created and
      repaired. The forces required to pull the fingertips to the palm after serial
      tendon advancements were measured. There was a near linear increase in the force
      required for making a fist with shortening up to 2.5 cm. The force required to
      make a fist should be taken into account when considering the limit of 'safe'
      tendon shortening in delayed repair of jersey finger injuries. 

PMID- 25969413
TI  - Trans-scaphoid-perilunate dislocation with an ulnar nerve injury.

PMID- 25969414
TI  - Evaluation of regional gastrointestinal absorption of edoxaban using the enterion
      capsule.
AB  - Two studies in healthy subjects assessed the absorption of edoxaban when
      delivered to specific locations within the gastrointestinal tract using Enterion
      capsules. In study 1 (single-dose, 4-way crossover), 8 participants received
      edoxaban 60 mg as immediate-release (IR) tablets (treatment A), as powder
      formulation delivered to the distal small bowel (treatment B) or ascending colon
      (treatment C), or as an aqueous suspension delivered to the ascending colon
      (treatment D). In study 2 (single-dose, 2-way crossover), 10 participants
      received edoxaban 30 mg as IR tablets (treatment E) or in granulate formulation
      with fumaric acid 50 mg, added to acidify the local gastrointestinal tract and
      enhance solubility, delivered to the ascending colon (treatment F). Peak and
      total exposure following targeted drug delivery to the distal gastrointestinal
      tract were significantly lower than with IR tablet delivery. In study 1, total
      exposure ratios of treatments B, C, and D compared with A were 14.9%, 7.9%, and
      6.1%, respectively. In study 2, relative total exposure was 12.6% for treatment F
      despite the fumaric acid. Time to peak concentration was longer with higher
      variability for edoxaban delivered to the distal gastrointestinal tract compared
      with the IR tablet. These data indicate that edoxaban absorption occurs
      predominantly in the proximal small intestine.

PMID- 25969415
TI  - Diagnostic accuracy of the Whooley depression tool in older adults in UK primary
      care.
AB  - PURPOSE OF RESEARCH: To validate the Whooley questions as a screening tool for
      depression amongst a population of older adults in UK primary care. OBJECTIVE: To
      assess the diagnostic performance of the Whooley questions as a screening tool
      for depression amongst older adults in UK primary care. PARTICIPANTS: A cross
      sectional validation study was conducted with 766 patients aged >=75 from UK
      primary care, recruited via 17 general practices based in the North of England
      during the pilot phase of a randomized controlled trial. MAIN OUTCOME MEASURES:
      Sensitivity, specificity and likelihood ratios comparing the index test (two
      Whooley questions) with a diagnosis of major depressive disorder (MDD)
      ascertained by the reference standard Mini International Neuropsychiatric
      Interview (MINI). RESULTS: The two screening questions had a sensitivity of 94.3%
      (95% confidence interval, 80.8-99.3%) and specificity of 62.7% (95% confidence
      interval, 59.0-66.2%). The likelihood ratio for a positive test was 2.5 (95%
      confidence interval, 2.2-2.9) and the likelihood ratio for a negative test was
      0.09 (95% confidence interval, 0.02-0.35). CONCLUSION: The two Whooley questions
      missed few cases of depression. However, they were responsible for a high rate of
      false positives. This creates additional burden on general practitioners, to
      conduct more detailed investigation on patients who screen positive, but many of
      whom turn out not to have MDD.

PMID- 25969416
TI  - Peptide-laden mesoporous silica nanoparticles with promoted bioactivity and osteo
      differentiation ability for bone tissue engineering.
AB  - Combination of mesoporous silica materials and bioactive factors is a promising
      niche-mimetic solution as a hybrid bone substitution for bone tissue engineering.
      In this work, we have synthesized biocompatible silica-based nanoparticles with
      abundant mesoporous structure, and incorporated bone-forming peptide (BFP)
      derived from bone morphogenetic protein-7 (BMP-7) into the mesoporous silica
      nanoparticles (MSNs) to obtain a slow-release system for osteogenic factor
      delivery. The chemical characterization demonstrates that the small osteogenic
      peptide is encapsulated in the mesoporous successfully, and the nitrogen
      adsorption-desorption isotherms suggest that the peptide encapsulation has no
      influence on mesoporous structure of MSNs. In the cell experiment, the peptide
      laden MSNs (p-MSNs) show higher MG-63 cell proliferation, spreading and alkaline
      phosphatase (ALP) activity than the bare MSNs, indicating good in vitro
      cytocompatibility. Simultaneously, the osteogenesis-related proteins expression
      and calcium mineral deposition disclose enhanced osteo-differentiation of human
      mesenchymal stem cells (hMSCs) under the stimulation of the p-MSNs, confirming
      that BFP released from MSNs could significantly promote the osteogenic
      differentiation of hMSCs, especially at 500MUg/mL of p-MSNs concentration. The
      peptide-modified MSNs with better bioactivity and osteogenic differentiation make
      it a potential candidate as bioactive material for bone repairing, bone
      regeneration, and bio-implant coating applications. 

PMID- 25969417
TI  - The influence of novel gemini surfactants containing cycloalkyl side-chains on
      the structural phases of DNA in solution.
AB  - Very important to gene therapy is the delivery system of the nucleic acids
      (called a vector), which will enhance the efficiency of the transport of new DNA
      into cells whilst protecting against damage. A promising alternative to the
      currently used viral vectors are the systems based on amphiphilic compounds -
      lipoplexes. Among them, gemini surfactants, which consist of two hydrophobic
      chains and two cationic heads connected by a linker - spacer group, appear to be
      promising candidates. The subject of this study involves two gemini surfactants,
      alkoxy derivatives of bis-imidazolium quaternary salts, differing in the length
      of their spacer groups and how they interact with two types of salmon sperm DNA
      (low and high molecular weight (MW)) or plasmid DNA (pDNA). The mixtures of
      gemini surfactants with nucleic acids of differing p/n ratios (positive-to
      negative charge ratio) were characterised by small angle X-ray scattering (SAXS)
      of synchrotron radiation, dynamic light scattering (DLS), circular dichroism (CD)
      spectroscopy, atomic force microscopy (AFM), transmission electron microscopy
      (TEM) and gel electrophoresis techniques. This analysis allows for the selection
      of the most suitable and promising candidates for non-viral vectors in gene
      therapy, determination of the conditions needed to form stable complexes,
      identification of conformational changes in the DNA molecules upon interactions
      with gemini surfactants and in some cases, determination of the structures formed
      in these lipoplexes. 

PMID- 25969418
TI  - Candida rugosa lipase immobilization on hydrophilic charged gold nanoparticles as
      promising biocatalysts: Activity and stability investigations.
AB  - In this work, a simple and versatile methodology to obtain two different
      bioconjugated systems has been developed by the immobilization of Candida rugosa
      lipase (CRL) on hydrophilic gold nanoparticles functionalized with 2
      diethylaminoethanethiol hydrochloride (DEA) or with sodium 3-mercapto-1
      propanesulfonate (3MPS), namely Au-DEA@CRL and Au-3MPS@CRL. Both spectroscopic
      and morphological properties of metal nanoparticles have been deeply
      investigated. The enzyme loading and lipolytic activity of AuNPs@CRL
      bioconjugates have been studied with respect to different surface
      functionalization and compared with the free enzyme. Some physical and chemical
      parameters had a strong effect on enzyme activity and stability, that were
      improved in the case of the Au-DEA@CRL bioconjugate, which showed a remarkable
      biocatalytic performance (95% of residual lipolytic activity compared with free
      CRL) and stability in experimental conditions concerning pH (range 5-8) and
      temperature (range 20-60 degrees C), as often required for the industrial scale
      up of catalytic systems. 

PMID- 25969419
TI  - A rhenium tris-carbonyl derivative as a model molecule for incorporation into
      phospholipid assemblies for skin applications.
AB  - A rhenium tris-carbonyl derivative (fac-[Re(CO)3Cl(2-(1-dodecyl-1H-1,2,3,triazol
      4-yl)-pyridine)]) was incorporated into phospholipid assemblies, called
      bicosomes, and the penetration of this molecule into skin was monitored using
      Fourier-transform infrared microspectroscopy (FTIR). To evaluate the capacity of
      bicosomes to promote the penetration of this derivative, the skin penetration of
      the Re(CO)3 derivative dissolved in dimethyl sulfoxide (DMSO), a typical
      enhancer, was also studied. Dynamic light scattering results (DLS) showed an
      increase in the size of the bicosomes with the incorporation of the Re(CO)3
      derivative, and the FTIR microspectroscopy showed that the Re(CO)3 derivative
      incorporated in bicosomes penetrated deeper into the skin than when dissolved in
      DMSO. When this molecule was applied on the skin using the bicosomes, 60% of the
      Re(CO)3 derivative was retained in the stratum corneum (SC) and 40% reached the
      epidermis (Epi). Otherwise, the application of this molecule via DMSO resulted in
      95% of the Re(CO)3 derivative being in the SC and only 5% reaching the Epi. Using
      a Re(CO)3 derivative with a dodecyl-chain as a model molecule, it was possible to
      determine the distribution of molecules with similar physicochemical
      characteristics in the skin using bicosomes. This fact makes these nanostructures
      promising vehicles for the application of lipophilic molecules inside the skin. 

PMID- 25969420
TI  - Kinin B1 Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice.
AB  - The effects of kinin B1 receptor (B1 R) deletion were examined on femur bone
      regeneration in streptozotocin (STZ)-type 1 diabetes. Diabetes induction in wild
      type C57/BL6 (WTC57BL6) mice led to decrease in body weight and hyperglycemia,
      compared to the non-diabetic group of the same strain. The lack of B1 R did not
      affect STZ-elicited body weight loss, but partially prevented hyperglycemia.
      Diabetic mice had a clear delay in bone regeneration, and displayed large areas
      of loose connective tissue within the defects, with a reduced expression of the
      mineralization-related protein osteonectin, when compared to the non-diabetic
      WTC57/BL6. The non-diabetic and diabetic B1 R knockout (B1 RKO) mice had bone
      regeneration levels and osteonectin expression comparable to that seen in control
      WTC57/BL6 mice. WTC57/BL6 STZ-diabetic mice also showed a marked reduction of
      collagen contents, with increased immunolabeling for the apoptosis marker caspase
      3, whereas diabetic B1 RKO had collagen levels and caspase-3 activity comparable
      to those observed in non-diabetic WTC57/BL6 or B1 RKO mice. No significant
      difference was detected in the number of tartrate-resistant acid phosphatase
      (TRAP)-stained cells, or in RANK/RANKL/OPG system immunolabeling throughout the
      experimental groups. Data bring novel evidence on the relevance of kinin B1 R
      under type 1 diabetes with regards to its role in bone regeneration.

PMID- 25969421
TI  - Membrane lipid therapy: Modulation of the cell membrane composition and structure
      as a molecular base for drug discovery and new disease treatment.
AB  - Nowadays we understand cell membranes not as a simple double lipid layer but as a
      collection of complex and dynamic protein-lipid structures and microdomains that
      serve as functional platforms for interacting signaling lipids and proteins.
      Membrane lipids and lipid structures participate directly as messengers or
      regulators of signal transduction. In addition, protein-lipid interactions
      participate in the localization of signaling protein partners to specific
      membrane microdomains. Thus, lipid alterations change cell signaling that are
      associated with a variety of diseases including cancer, obesity,
      neurodegenerative disorders, cardiovascular pathologies, etc. This article
      reviews the newly emerging field of membrane lipid therapy which involves the
      pharmacological regulation of membrane lipid composition and structure for the
      treatment of diseases. Membrane lipid therapy proposes the use of new molecules
      specifically designed to modify membrane lipid structures and microdomains as
      pharmaceutical disease-modifying agents by reversing the malfunction or altering
      the expression of disease-specific protein or lipid signal cascades. Here, we
      provide an in-depth analysis of this emerging field, especially its molecular
      bases and its relevance to the development of innovative therapeutic approaches. 

PMID- 25969422
TI  - Abuse liability assessment of hydrocodone under current draft regulatory
      guidelines.
AB  - INTRODUCTION: The abuse liability of hydrocodone was assessed in male Sprague
      Dawley rats under the European Medicines Agency, the International Commission on
      Harmonisation, and the U.S. Food & Drug Administration draft guidelines for the
      non-clinical investigation of the dependence potential of medicinal products.
      METHODS: Self-administration, drug discrimination, and repeat-dose two week
      dependence liability studies were conducted to compare hydrocodone to the
      prototypical opiates, morphine and oxycodone. RESULTS: Hydrocodone was self
      administered, produced an opiate-like subjective discriminative generalization
      profile and produced a significant discontinuation syndrome following abrupt
      treatment cessation that was quantitatively and qualitatively similar to morphine
      and/or oxycodone. CONCLUSION: Hydrocodone has abuse liability more similar to
      Schedule II opiates than other Schedule III compounds currently controlled under
      the U.S. Controlled Substance Act.

PMID- 25969423
TI  - Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel
      for bone tissue regeneration: in vitro and in vivo characteristics.
AB  - Reports on the local delivery of drug loaded injectable hydrogels for bone
      regeneration are currently limited. This study assessed the effect of controlled
      simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo.
      We successfully manufactured and evaluated thermo-sensitive poly(d,l-lactide-co
      glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) triblock
      copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this
      hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and
      osteoblastic differentiation was analyzed after cultivation with the hydrogel
      extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in
      mineralization and osteogenic gene expression compared to the other two groups.
      Additionally, the characteristics of this composite in vivo were demonstrated
      using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA
      hydrogel showed increased new bone formation compared to samples treated with
      PLGA-PEG-PLGA and control samples. The results of this study suggest that
      SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing.

PMID- 25969424
TI  - Embedding a Recovery Orientation into Neuroscience Research: Involving People
      with a Lived Experience in Research Activity.
AB  - This paper highlights the importance and value of involving people with a lived
      experience of mental ill health and recovery in neuroscience research activity.
      In this era of recovery oriented service delivery, involving people with the
      lived experience of mental illness in neuroscience research extends beyond their
      participation as "subjects". The recovery paradigm reconceptualises people with
      the lived experience of mental ill health as experts by experience. To support
      this contribution, local policies and procedures, recovery-oriented training for
      neuroscience researchers, and dialogue about the practical applications of
      neuroscience research, are required. 

PMID- 25969425
TI  - Transcriptional regulatory network of SOX4 during myoblast differentiation.
AB  - The construction of transcriptional regulatory networks of transcription factors
      (TFs) has become more important and attractive to understand the alterations of
      binding protein-dependent transcriptional activity that governs the changes in
      spatiotemporal expression of TF target genes required in various cellular
      processes. Therefore, identification of new inner modules including target genes
      and protein interactions involved in unveiled TF-based transcription networks is
      currently in the research spotlight. In this study, we reveal a possible SOX4
      centered transcriptional network by the identification of novel binding partners
      and target genes of the TF SOX4 using various screening techniques. Lamin B2,
      barrier to autointegration factor 1, and apolipoprotein C-III were identified as
      novel interacting partners of SOX4 by yeast two-hybrid screening, and the genes
      encoding lysosomal-associated membrane protein 1, ubiquitin-conjugating enzyme
      E2S, and Map2k2 were identified as putative target genes of SOX4. Differently
      from the computational networks of TFs, we revealed a SOX4-centered physical
      network during myoblast differentiation. These results will provide opportunities
      to better understand the SOX4-centered transcriptional regulation network and TF
      based specific gene expression in various cellular environments. 

PMID- 25969426
TI  - The regulator of G-protein signaling 18 regulates platelet aggregation,
      hemostasis and thrombosis.
AB  - Regulators of G protein signaling (RGS) proteins are known to interact with and
      negatively regulate/turn-off G protein activation. RGS18 is identified as an R4
      subfamily member of this family with specific expression in hematopoietic
      progenitors, myeloerythroid cells, megakaryocytes and platelets. Studies focused
      on understanding its function in platelet biology have been limited, in part, due
      to lack of pharmacological inhibitors. Thus, the present study investigated the
      function of RGS18 in platelets, using the RGS18 knockout mouse model (RGS18(-/
      )). We identified phenotypic differences between RGS18(-/-) and wild-type (WT)
      mice, and show that RGS18 plays a significant role in hemostasis and thrombosis.
      Hence, RGS18 deficiency markedly shortened bleeding as well as occlusion times
      (in vivo). Furthermore, RGS18(-/-) platelets displayed hyper-responsiveness with
      regards to agonist induced aggregation (in vitro). This gain of function
      phenotype may serve as the mechanism or explain, at least in part, the enhanced
      hemostasis and thrombosis phenotype observed in the RGS18 deletion mice.
      Collectively, our findings provide valuable insight and highlight a critical and
      direct role for RGS18 in modulating platelet function. 

PMID- 25969427
TI  - Reduced high density lipoprotein cholesterol in severe hypertriglyceridemic
      ApoCIII transgenic mice via lowered hepatic ApoAI synthesis.
AB  - Clinical and epidemiological investigations confirm that patients with loss-of
      function mutations (R19X, etc.) in Apolipoprotein CIII (ApoCIII) showed
      beneficial lipid profile including decreased plasma triglyceride and increased
      high density lipoprotein (HDL) levels. However, whether HDL level would be
      reduced in hypertriglyceridemia (HTG) induced by high ApoCIII expression has not
      been demonstrated yet. Here we showed, ApoCIII transgenic mice (ApoCIIItg)
      displayed severe HTG and had significantly lower HDL level. Analysis of
      apolipoproteins in lipoprotein fractions by SDS-PAGE revealed marked decrease of
      apolipoprotein AI (ApoAI) in HDL in transgenic mice compared with the wild type
      mice (WT) as controls. Further examination demonstrated that hepatic but not
      intestinal ApoAI mRNA was significantly reduced. Therefore, the decreased ApoAI
      synthesis might be accounted for the lower plasma HDL level in ApoCIII transgenic
      mice. 

PMID- 25969428
TI  - Regulation of burstiness by network-driven activation.
AB  - We prove that complex networks of interactions have the capacity to regulate and
      buffer unpredictable fluctuations in production events. We show that non-bursty
      network-driven activation dynamics can effectively regulate the level of
      burstiness in the production of nodes, which can be enhanced or reduced.
      Burstiness can be induced even when the endogenous inter-event time distribution
      of nodes' production is non-bursty. We find that hubs tend to be less susceptible
      to the networked regulatory effects than low degree nodes. Our results have
      important implications for the analysis and engineering of bursty activity in a
      range of systems, from communication networks to transcription and translation of
      genes into proteins in cells. 

PMID- 25969429
TI  - Impact of nucleation conditions on diameter modulation of GaAs nanowires.
AB  - Diameter-modulated nanowires can be used to impart unique properties to nanowire
      based devices. Here, diameter modulation along Au-seeded GaAs nanowires was
      achieved by varying the flux of the III and V precursors during growth.
      Furthermore, three different types of [111]B-oriented nanowires were observed to
      display distinct differences in diameter modulation, growth rate, and cross
      sectional shape. These differences are attributed to the presence of multiple
      distinct Au-Ga seed particle phases at the growth temperature of 420  degrees C.
      We show that the diameter modulation behavior can be modified by the growth
      conditions during nanowire nucleation, including temperature, V/III ratio,
      substrate orientation, and seed particle size. These results demonstrate the
      general viability of flow-controlled diameter modulation for compound
      semiconductors and highlight both opportunities and challenges that can arise
      from using compound-forming alloys to seed nanowire growth. 

PMID- 25969431
TI  - Prophylactic treatment with S100A9 inhibitor paquinimod reduces pathology in
      experimental collagenase-induced osteoarthritis.
AB  - OBJECTIVES: Alarmins S100A8/A9 regulate pathology in experimental osteoarthritis
      (OA). Paquinimod is an immunomodulatory compound preventing S100A9 binding to TLR
      4. We investigated the effect of paquinimod on experimental OA and human OA
      synovium. MATERIALS AND METHODS: Two OA mouse models differing in level of
      synovial activation were treated prophylactic with paquinimod. Synovial
      thickening, osteophyte size and cartilage damage were measured histologically,
      using an arbitrary score, adapted Pritzker OARSI score or imaging software,
      respectively. Human OA synovia were stimulated with S100A9, with or without
      paquinimod. RESULTS: Paquinimod treatment of collagenase-induced OA (CIOA)
      resulted in significantly reduced synovial thickening (57%), osteophyte size at
      the medial femur (66%) and cruciate ligaments (67%) and cartilage damage at the
      medial tibia (47%) and femur (75%; n=7, untreated n=6). In contrast, paquinimod
      did not reduce osteophyte size and reduced cartilage damage at one location only
      in destabilised medial meniscus, an OA model with considerably lower synovial
      activation compared with CIOA. In human OA synovium, paquinimod blocked
      proinflammatory (interleukin (IL)-6, IL-8, tumour necrosis factor-alpha) and
      catabolic (matrix metalloproteinases 1 and 3) factors induced by S100A9 (n=5).
      CONCLUSIONS: Prophylactic treatment of paquinimod reduces synovial activation,
      osteophyte formation and cartilage damage in experimental OA with high synovial
      activation (CIOA) and ameliorates pathological effects of S100A9 in OA synovium
      ex vivo.

PMID- 25969432
TI  - Customization of a Severity of Illness Score Using Local Electronic Medical
      Record Data.
AB  - PURPOSE: Severity of illness (SOI) scores are traditionally based on archival
      data collected from a wide range of clinical settings. Mortality prediction using
      SOI scores tends to underperform when applied to contemporary cases or those that
      differ from the case-mix of the original derivation cohorts. We investigated the
      use of local clinical data captured from hospital electronic medical records
      (EMRs) to improve the predictive performance of traditional severity of illness
      scoring. METHODS: We conducted a retrospective analysis using data from the
      Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database,
      which contains clinical data from the Beth Israel Deaconess Medical Center in
      Boston, Massachusetts. A total of 17 490 intensive care unit (ICU) admissions
      with complete data were included, from 4 different service types: medical ICU,
      surgical ICU, coronary care unit, and cardiac surgery recovery unit. We developed
      customized SOI scores trained on data from each service type, using the clinical
      variables employed in the Simplified Acute Physiology Score (SAPS). In-hospital,
      30-day, and 2-year mortality predictions were compared with those obtained from
      using the original SAPS using the area under the receiver-operating
      characteristics curve (AUROC) as well as the area under the precision-recall
      curve (AUPRC). Test performance in different cohorts stratified by severity of
      organ injury was also evaluated. RESULTS: Most customized scores (30 of 39)
      significantly outperformed SAPS with respect to both AUROC and AUPRC.
      Enhancements over SAPS were greatest for patients undergoing cardiovascular
      surgery and for prediction of 2-year mortality. CONCLUSIONS: Custom models based
      on ICU-specific data provided better mortality prediction than traditional SAPS
      scoring using the same predictor variables. Our local data approach demonstrates
      the value of electronic data capture in the ICU, of secondary uses of EMR data,
      and of local customization of SOI scoring.

PMID- 25969433
TI  - Critical care in the emergency department: acute kidney injury.
AB  - Acute kidney injury (AKI) is common among emergency department patients admitted
      to hospital. There is evidence of inadequate management of the condition leading
      to adverse outcomes. We present an illustrative case of AKI complicating a
      gastrointestinal disorder in an older adult. We discuss the clinical
      presentation, assessment and management of AKI with reference to recent consensus
      guidelines on classification and treatment. 

PMID- 25969430
TI  - Treating rheumatoid arthritis to target: 2014 update of the recommendations of an
      international task force.
AB  - BACKGROUND: Reaching the therapeutic target of remission or low-disease activity
      has improved outcomes in patients with rheumatoid arthritis (RA) significantly.
      The treat-to-target recommendations, formulated in 2010, have provided a basis
      for implementation of a strategic approach towards this therapeutic goal in
      routine clinical practice, but these recommendations need to be re-evaluated for
      appropriateness and practicability in the light of new insights. OBJECTIVE: To
      update the 2010 treat-to-target recommendations based on systematic literature
      reviews (SLR) and expert opinion. METHODS: A task force of rheumatologists,
      patients and a nurse specialist assessed the SLR results and evaluated the
      individual items of the 2010 recommendations accordingly, reformulating many of
      the items. These were subsequently discussed, amended and voted upon by >40
      experts, including 5 patients, from various regions of the world. Levels of
      evidence, strengths of recommendations and levels of agreement were derived.
      RESULTS: The update resulted in 4 overarching principles and 10 recommendations.
      The previous recommendations were partly adapted and their order changed as
      deemed appropriate in terms of importance in the view of the experts. The SLR had
      now provided also data for the effectiveness of targeting low-disease activity or
      remission in established rather than only early disease. The role of
      comorbidities, including their potential to preclude treatment intensification,
      was highlighted more strongly than before. The treatment aim was again defined as
      remission with low-disease activity being an alternative goal especially in
      patients with long-standing disease. Regular follow-up (every 1-3 months during
      active disease) with according therapeutic adaptations to reach the desired state
      was recommended. Follow-up examinations ought to employ composite measures of
      disease activity that include joint counts. Additional items provide further
      details for particular aspects of the disease, especially comorbidity and shared
      decision-making with the patient. Levels of evidence had increased for many items
      compared with the 2010 recommendations, and levels of agreement were very high
      for most of the individual recommendations (>=9/10). CONCLUSIONS: The 4
      overarching principles and 10 recommendations are based on stronger evidence than
      before and are supposed to inform patients, rheumatologists and other
      stakeholders about strategies to reach optimal outcomes of RA.

PMID- 25969434
TI  - Characterizing Pressure and Flow Rate for Aqueous Immersion Surgery.
AB  - Hemorrhage control during surgery remains a major clinical challenge for
      surgeons. Bleeding can affect the safety and efficacy of any surgical procedure.
      There are well-established methods to address this side-effect of surgery, but
      all current technologies require the surgeon to direct attention to hemostasis
      rather than the continuance of the procedure. We have developed a novel surgical
      method, titled aqueous immersion surgery (AIS), that is able to sustain a
      bloodless surgical field by providing a controlled hydraulic pressure (immersion
      pressure) on the bleeding site. Together with the replenishment of an immersion
      fluid (immersion flow rate), AIS maintains optical clarity of the surgical field.
      This numerical study was undertaken to investigate the influence of the rate
      exchange of the immersion fluid on the concentration of blood, hence optical
      clarity therein. A 3-dimensional multicomponent simulation was performed to
      evaluate the mixing of blood from an idealized arterial bleeding vessel under
      pulsatile conditions. With an increase in immersion pressure, bleeding was
      reduced and increased perfusion was observed. Additionally, the magnitude and
      direction of the flow field affected the deflection of the bleeding trajectory
      and, in turn, affected the removal rate of blood from the surgical field. For an
      idealized case, an optimal immersion flow rate was found for immersion pressures
      of 100 and 110 mm Hg. From this study, fluid dynamic guidelines are postulated to
      support future development of AIS. 

PMID- 25969435
TI  - Three-Dimensional Changes in the Midface Following Malar Calcium Hydroxyapatite
      Injection in a Cadaver Model.
AB  - BACKGROUND: Three-dimensional (3D) changes in the midface following malar calcium
      hydroxyapatite (CaHa) injection have not been systematically analyzed.
      OBJECTIVES: The authors analyzed 3D volume changes in midface and naso-labial
      fold (NLF) volume, as well as lateral movement in the NLF/naso-labial crease
      (NLC) junction following malar injection of CaHa in a cadaver model. METHODS: A
      single surgeon injected CaHa in the supraperiosteal plane. Sequential images were
      obtained with the VECTRA 3D system pre- and post-1.5- and 3-cc CaHa injections.
      All measurements were performed by a single examiner. Injection location was
      verified anatomically. RESULTS: Injections were performed in 16 fresh cadaver
      hemi-faces. Maximal increases in projection were centered on the malar injection
      site, with associated decreases in projection and volume in the infero-medial
      locations. Relative mean increases in volume of 3.16 cc and 4.94 cc were observed
      following the 1.5-cc and 3-cc injections, respectively. There was a relative
      decrease in the volume of the NLF of -0.3 cc and -0.4 cc following the 1.5- and 3
      cc injections, respectively. Injection of CaHa was associated with lateral
      movements of the NLF-NLC junction at the level of the nasal sill, philtral
      columns, and oral commissure, measuring 2.7, 2.5, and 1.9 mm and 2.8, 2.9, and
      2.4 mm following the 1.5- and 3-cc injections, respectively. Anatomical
      dissection verified the location in the supraperiosteal space and within the
      middle malar fat pad. CONCLUSIONS: Following malar CaHa injection, 3D
      photographic analysis showed a measureable lifting effect with recruitment of
      ptotic tissue and lateral movement of the NLF-NLC junction in a cadaver model.

PMID- 25969436
TI  - Preliminary Report on an Objective, Fast, and Reproducible Method to Measure the
      Effectiveness of Botulinum Toxin Type A.
AB  - BACKGROUND: The injection of botulinum toxin type A for cosmetic proposes is a
      popular procedure, although the interpretation of its effectiveness still poses a
      challenge. In fact, although the methods that evaluate the efficacy of the
      treatment are validated and reliable, they are usually based on subjective
      scales, while an objective and quantitative scale is still needed. OBJECTIVES: I
      propose an objective, fast, and reproducible method to evaluate the severity of
      wrinkles with a three-dimensional imaging and texture analysis. METHODS: Digital
      Analysis of the Cutaneous Surface (DACS) is employed to analyze cutaneous
      texture. Measures are performed in the glabellar area before and one month after
      infiltration of 15 units of onabotulinumtoxin-A. RESULTS: Eight women were
      included in this study. DACS was able to detect improvements in all cases. On
      average, static lines decreased by 12.4% and dynamic lines by 41.2%. CONCLUSIONS:
      DACS provides an objective, direct, fast, and reproducible method to measure the
      results of botulinum toxin type A usage. It avoids the use of subjective scores,
      gives a direct measure of the wrinkles, is simple to perform, and allows the
      operator to analyze only the desired area. LEVEL OF EVIDENCE: 4 Therapeutic.

PMID- 25969437
TI  - Low P-wave amplitude (<0.1 mV) in lead I is associated with displaced inter
      atrial conduction and clinical recurrence of paroxysmal atrial fibrillation after
      radiofrequency catheter ablation.
AB  - AIMS: We hypothesized that P-wave amplitude in lead I is related to left atrial
      (LA) remodelling and inter-atrial conduction pattern, and has a predictive value
      for recurrence after radiofrequency catheter ablation (RFCA) among patients with
      paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: A total of 525
      consecutive patients with PAF (76% male, 56 +/- 12 years old) who underwent RFCA
      were included. We compared pre-procedural sinus rhythm electrocardiograms without
      antiarrhythmic drug effect with LA volume (CT), LA voltage (NavX), the earliest
      activation site (EAS) conduction pattern of LA, and clinical recurrence rate. P
      wave amplitude in lead I was significantly lower in patients with recurrence than
      in those that remained in sinus rhythm (P < 0.001) during 21 +/- 10-month follow
      up. P-wave amplitude in lead I was linearly correlated with LA voltage (beta =
      2.52, 95% CI 0.606-4.425, P = 0.010), LA conduction velocity (beta = 1.91, 95% CI
      0.941-2.876, P < 0.001), and low septal displacement of EAS (beta = -1.67, 95% CI
      -2.352 to -0.996, P < 0.001). P-wave amplitudes <0.1 mV in lead I were
      independently associated with clinical recurrence of AF on multivariate Cox
      regression analysis (adjusted HR 2.163, 95% CI 1.307-3.581, P = 0.003). The
      integrated area under the curves was 0.705 (95% CI 0.655-0.755). CONCLUSION: Low
      P-wave amplitude (<0.1 mV) in lead I is related to LA remodelling and displaced
      inter-atrial conduction pattern to low septum, and independently predicts
      clinical recurrence after RFCA in patients with PAF.

PMID- 25969438
TI  - A new trick to a routine procedure: taking the fear out of the axillary vein
      stick using the 35 degrees  caudal view.
AB  - AIMS: The axillary vein is frequently used to implant pacemaker and defibrillator
      leads. We describe a technique utilizing the caudal fluoroscopic view to
      facilitate axillary venous access without contrast. METHODS AND RESULTS: Outcomes
      of device implants or upgrades utilizing this technique were examined during a 1
      year period at our institution. Of 229 consecutive implants, only 9 patients
      required an alternate technique for lead implantation. There were zero cases of
      pneumothorax. CONCLUSIONS: The caudal view allows for optimal appreciation of the
      anterior border of the lung and the first rib. This simple technique increases
      the implanter's appreciation of and control over the access needle depth relative
      to the lung and first rib, thereby reducing pneumothorax risk.

PMID- 25969439
TI  - Ineffective central nervous system HIV suppression of once-a-day maraviroc and
      ritonavir-boosted darunavir dual therapy: four case reports.
AB  - Novel two-drug combinations including a protease inhibitor are an attractive
      nucleoside reverse transcriptase inhibitor sparing option for some patients,
      particularly as a switch strategy. We have used the two-drug combination of
      maraviroc and darunavir/ritonavir once a day as a switch strategy in patients
      with stable low or undetectable plasma HIV viral loads, but identified four
      patients who failed on this combination, indicating it may be insufficient to
      prevent replication of neurotropic HIV in treatment-experienced patients. Further
      investigation of our cases highlighted the need for a better understanding of the
      plasma and cerebro-spinal fluid (CSF) pharmacodynamics of these drugs. 

PMID- 25969440
TI  - Bifidobacteria Expressing Tumstatin Protein for Antitumor Therapy in Tumor
      Bearing Mice.
AB  - Tumstatin (Tum) is a powerful angiostatin that inhibits proliferation and induces
      apoptosis of tumorous vascular endothelial cells. A nonpathogenic and anaerobic
      bacterium, Bifidobacterium longum (BL), selectively localizes to and proliferates
      in the hypoxia location within solid tumor. The aims of this study were to
      develop a novel delivery system for Tum using engineered Bifidobacterium and to
      investigate the inhibitory effect of Tum on tumor in mice. A vector that enabled
      the expression of Tum under the control of the pBBADs promoter of BL was
      constructed and transformed into BL NCC2705 by electroporation. The mouse colon
      carcinoma cells CT26 (1 * 10(7)/mL) were subcutaneously inserted in the left
      armpit of BALB/c mice. The tumor-bearing mice were treated with Tum-transformed
      BL, and green fluorescent protein (GFP)-transformed BL was used as a negative
      control. The microvessel density (MVD) in the transplanted tumor was determined,
      and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'
      triphosphate nick end labeling was used to detect apoptosis of vascular
      endothelial cells in transplanted tumor. The in vitro expression of Tum was
      examined in BL after l-arabinose induction. Bifidobacterium longum with pBBAD-Tum
      (BL-Tum) showed significant antitumor effect in tumor-bearing mice. The weight,
      volume, growth, and MVD, as well as the percentage of apoptotic vascular
      endothelial cells of transplanted tumors in the tumor-bearing mice treated with
      Tum-transformed BL were all significantly lower than those in the GFP negative
      control group. Intragastric administration, injection in tumor and vena caudalis
      injection of Tum-transformed BL exerted marked antitumor effects in tumor-bearing
      mice. This is the first demonstration of the utilization of Tum-transformed BL as
      a specific gene delivery system for treating tumor.

PMID- 25969441
TI  - The Lethality Screen: The Predictive Validity of an Intimate Partner Violence
      Risk Assessment for Use by First Responders.
AB  - This research is an examination of the predictive validity of the Lethality
      Screen, a tool used in conjunction with the Lethality Assessment Program (LAP).
      This intimate partner violence (IPV) risk assessment is an 11-item version of the
      Danger Assessment (DA) that was designed to be user-friendly for first responders
      and to maximize sensitivity. Participants ( N = 254) were recruited into the
      study at the scene of police-involved IPV incidents in one Southwestern state and
      subsequently participated in two structured telephone interviews approximately 7
      months apart. These analyses provide evidence that the Lethality Screen has
      considerable sensitivity (92%-93%) and a high negative predictive value (93%-96%)
      for near lethal and severe violence. However, specificity was low (21%). The
      Lethality Screen also has good agreement with the DA and IPV survivors'
      perception of risk. The high sensitivity and low specificity should be considered
      carefully when determining whether the Lethality Screen is appropriate for
      particular areas of practice with IPV survivors and/or perpetrators.

PMID- 25969442
TI  - Dating Violence in Mexican College Students: Evaluation of an Educational
      Workshop.
AB  - Dating violence represents an important health problem among adolescents and
      young adults, not only because of its high prevalence but also because of its
      negative consequences for individual and social development. Educational programs
      aimed at the prevention and reduction of aggression are indispensable; therefore,
      the aims of this study were to assess perception and attitudes toward dating
      violence, and to evaluate the effectiveness of an educational workshop among
      college students. A total of 212 students from a public university in Mexico City
      participated in the study. The participants were distributed into two groups: the
      intervention group (IG; which received a workshop on dating violence) and the
      control group (CG; which did not participate in the workshop). A self-reported
      questionnaire was applied to assess students' perception and attitudes toward
      violence. Means and standard deviations were calculated. In both groups, the
      comparison between pre- and post-evaluation scores was carried out using the test
      for matched pairs. The MANOVA test was performed for repeated measurements. The
      participants of the workshop showed positive changes in perception and attitudes
      toward dating violence, p < .0001; these changes were not observed in the CG, p =
      .98. Women in the IG showed a higher improvement than men, p = .04. Findings
      highlight the importance of creating long-term health promotion programs to
      improve human relationships, particularly in such important areas as dating
      violence.

PMID- 25969443
TI  - Dyadic Dynamics in Young Couples Reporting Dating Violence: An Actor-Partner
      Interdependence Model.
AB  - This study uses a combination of observational methods and dyadic data analysis
      to understand how boyfriends' and girlfriends' perpetration of dating violence
      (DV) may shape their own and their partners' problem-solving communication
      behaviors. A sample of 39 young heterosexual couples aged between 15 and 20 years
      (mean age = 17.8 years) completed a set of questionnaires and were observed
      during a 45-min dyadic interaction, which was coded using the Interactional
      Dimension Coding System (IDCS). Results suggest that neither boyfriends' nor
      girlfriends' own perpetration of DV was related to their display of positive and
      negative communication behaviors. However, estimates revealed significant partner
      effects, suggesting that negative communication behaviors displayed by girls and
      boys and positive communication behavior displayed by girls were associated to
      their partner's DV but not to their own. Such results confirm the need to shift
      our focus from an individual perspective to examining dyadic influences and
      processes involved in the couple system and the bidirectionality of violent
      relationships.

PMID- 25969444
TI  - Structural and sequencing analysis of local target DNA recognition by MLV
      integrase.
AB  - Target-site selection by retroviral integrase (IN) proteins profoundly affects
      viral pathogenesis. We describe the solution nuclear magnetic resonance structure
      of the Moloney murine leukemia virus IN (M-MLV) C-terminal domain (CTD) and a
      structural homology model of the catalytic core domain (CCD). In solution, the
      isolated MLV IN CTD adopts an SH3 domain fold flanked by a C-terminal
      unstructured tail. We generated a concordant MLV IN CCD structural model using
      SWISS-MODEL, MMM-tree and I-TASSER. Using the X-ray crystal structure of the
      prototype foamy virus IN target capture complex together with our MLV domain
      structures, residues within the CCD alpha2 helical region and the CTD beta1-beta2
      loop were predicted to bind target DNA. The role of these residues was analyzed
      in vivo through point mutants and motif interchanges. Viable viruses with
      substitutions at the IN CCD alpha2 helical region and the CTD beta1-beta2 loop
      were tested for effects on integration target site selection. Next-generation
      sequencing and analysis of integration target sequences indicate that the CCD
      alpha2 helical region, in particular P187, interacts with the sequences distal to
      the scissile bonds whereas the CTD beta1-beta2 loop binds to residues proximal to
      it. These findings validate our structural model and disclose IN-DNA interactions
      relevant to target site selection. 

PMID- 25969445
TI  - Human nucleolar protein Nop52 (RRP1/NNP-1) is involved in site 2 cleavage in
      internal transcribed spacer 1 of pre-rRNAs at early stages of ribosome
      biogenesis.
AB  - During the early steps of ribosome biogenesis in mammals, the two ribosomal
      subunits 40S and 60S are produced via splitting of the large 90S pre-ribosomal
      particle (90S) into pre-40S and pre-60S pre-ribosomal particles (pre-40S and pre
      60S). We previously proposed that replacement of fibrillarin by Nop52 (RRP1/NNP
      1) for the binding to p32 (C1QBP) is a key event that drives this splitting
      process. However, how the replacement by RRP1 is coupled with the endo- and/or
      exo-ribonucleolytic cleavage of pre-rRNA remains unknown. In this study, we
      demonstrate that RRP1 deficiency suppressed site 2 cleavage on ITS1 of 47S/45S,
      41S and 36S pre-rRNAs in human cells. RRP1 was also present in 90S and was
      localized in the dense fibrillar component of the nucleolus dependently on active
      RNA polymerase I transcription. In addition, double knockdown of XRN2 and RRP1
      revealed that RRP1 accelerated the site 2 cleavage of 47S, 45S and 41S pre-rRNAs.
      These data suggest that RRP1 is involved not only in competitive binding with
      fibrillarin to C1QBP on 90S but also in site 2 cleavage in ITS1 of pre-rRNAs at
      early stages of human ribosome biogenesis; thus, it is likely that RRP1
      integrates the cleavage of site 2 with the physical split of 90S into pre-40S and
      pre-60S. 

PMID- 25969446
TI  - The TOPCONS web server for consensus prediction of membrane protein topology and
      signal peptides.
AB  - TOPCONS (http://topcons.net/) is a widely used web server for consensus
      prediction of membrane protein topology. We hereby present a major update to the
      server, with some substantial improvements, including the following: (i) TOPCONS
      can now efficiently separate signal peptides from transmembrane regions. (ii) The
      server can now differentiate more successfully between globular and membrane
      proteins. (iii) The server now is even slightly faster, although a much larger
      database is used to generate the multiple sequence alignments. For most proteins,
      the final prediction is produced in a matter of seconds. (iv) The user-friendly
      interface is retained, with the additional feature of submitting batch files and
      accessing the server programmatically using standard interfaces, making it thus
      ideal for proteome-wide analyses. Indicatively, the user can now scan the entire
      human proteome in a few days. (v) For proteins with homology to a known 3D
      structure, the homology-inferred topology is also displayed. (vi) Finally, the
      combination of methods currently implemented achieves an overall increase in
      performance by 4% as compared to the currently available best-scoring methods and
      TOPCONS is the only method that can identify signal peptides and still maintain a
      state-of-the-art performance in topology predictions. 

PMID- 25969447
TI  - ClustVis: a web tool for visualizing clustering of multivariate data using
      Principal Component Analysis and heatmap.
AB  - The Principal Component Analysis (PCA) is a widely used method of reducing the
      dimensionality of high-dimensional data, often followed by visualizing two of the
      components on the scatterplot. Although widely used, the method is lacking an
      easy-to-use web interface that scientists with little programming skills could
      use to make plots of their own data. The same applies to creating heatmaps: it is
      possible to add conditional formatting for Excel cells to show colored heatmaps,
      but for more advanced features such as clustering and experimental annotations,
      more sophisticated analysis tools have to be used. We present a web tool called
      ClustVis that aims to have an intuitive user interface. Users can upload data
      from a simple delimited text file that can be created in a spreadsheet program.
      It is possible to modify data processing methods and the final appearance of the
      PCA and heatmap plots by using drop-down menus, text boxes, sliders etc.
      Appropriate defaults are given to reduce the time needed by the user to specify
      input parameters. As an output, users can download PCA plot and heatmap in one of
      the preferred file formats. This web server is freely available at
      http://biit.cs.ut.ee/clustvis/. 

PMID- 25969448
TI  - XPD localizes in mitochondria and protects the mitochondrial genome from
      oxidative DNA damage.
AB  - Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that
      plays essential roles in both transcription and nucleotide excision repair of
      nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria
      remains elusive. In this study, we provide the first evidence that XPD is
      localized in the inner membrane of mitochondria, and cells under oxidative stress
      showed an enhanced recruitment of XPD into mitochondrial compartment.
      Furthermore, mitochondrial reactive oxygen species production and levels of
      oxidative stress-induced mitochondrial DNA (mtDNA) common deletion were
      significantly elevated, whereas capacity for oxidative damage repair of mtDNA was
      markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD
      deficient human fibroblasts. Immunoprecipitation-mass spectrometry analysis was
      used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu
      translation elongation factor was detected to be physically interacted with XPD.
      Similar to the findings in XPD-deficient cells, mitochondrial common deletion and
      oxidative damage repair capacity in U2OS cells were found to be significantly
      altered after TUFM knock-down. Our findings clearly demonstrate that XPD plays
      crucial role(s) in protecting mitochondrial genome stability by facilitating an
      efficient repair of oxidative DNA damage in mitochondria. 

PMID- 25969449
TI  - GalaxyPepDock: a protein-peptide docking tool based on interaction similarity and
      energy optimization.
AB  - Protein-peptide interactions are involved in a wide range of biological processes
      and are attractive targets for therapeutic purposes because of their small
      interfaces. Therefore, effective protein-peptide docking techniques can provide
      the basis for potential therapeutic applications by enabling an atomic-level
      understanding of protein interactions. With the increasing number of protein
      peptide structures deposited in the protein data bank, the prediction accuracy of
      protein-peptide docking can be enhanced by utilizing the information provided by
      the database. The GalaxyPepDock web server, which is freely accessible at
      http://galaxy.seoklab.org/pepdock, performs similarity-based docking by finding
      templates from the database of experimentally determined structures and building
      models using energy-based optimization that allows for structural flexibility.
      The server can therefore effectively model the structural differences between the
      template and target protein-peptide complexes. The performance of GalaxyPepDock
      is superior to those of the other currently available web servers when tested on
      the PeptiDB set and on recently released complex structures. When tested on the
      CAPRI target 67, GalaxyPepDock generates models that are more accurate than the
      best server models submitted during the CAPRI blind prediction experiment. 

PMID- 25969450
TI  - IMP 2.0: a multi-species functional genomics portal for integration,
      visualization and prediction of protein functions and networks.
AB  - IMP (Integrative Multi-species Prediction), originally released in 2012, is an
      interactive web server that enables molecular biologists to interpret
      experimental results and to generate hypotheses in the context of a large cross
      organism compendium of functional predictions and networks. The system provides
      biologists with a framework to analyze their candidate gene sets in the context
      of functional networks, expanding or refining their sets using functional
      relationships predicted from integrated high-throughput data. IMP 2.0 integrates
      updated prior knowledge and data collections from the last three years in the
      seven supported organisms (Homo sapiens, Mus musculus, Rattus norvegicus,
      Drosophila melanogaster, Danio rerio, Caenorhabditis elegans, and Saccharomyces
      cerevisiae) and extends function prediction coverage to include human disease.
      IMP identifies homologs with conserved functional roles for disease knowledge
      transfer, allowing biologists to analyze disease contexts and predictions across
      all organisms. Additionally, IMP 2.0 implements a new flexible platform for
      experts to generate custom hypotheses about biological processes or diseases,
      making sophisticated data-driven methods easily accessible to researchers. IMP
      does not require any registration or installation and is freely available for use
      at http://imp.princeton.edu. 

PMID- 25969451
TI  - Semiautomated Sample Preparation for Protein Stability and Formulation Screening
      via Buffer Exchange.
AB  - A novel semiautomated buffer exchange process workflow was developed to enable
      efficient early protein formulation screening. An antibody fragment protein,
      BMSdab, was used to demonstrate the workflow. The process afforded 60% to 80%
      cycle time and scientist time savings and significant material efficiencies.
      These efficiencies ultimately facilitated execution of this stability work
      earlier in the drug development process, allowing this tool to inform the
      developability of potential candidates for development from a formulation
      perspective. To overcome the key technical challenges, the protein solution was
      buffer-exchanged by centrifuge filtration into formulations for stability
      screening in a 96-well plate with an ultrafiltration membrane, leveraging
      automated liquid handling and acoustic volume measurements to allow several
      cycles of exchanges. The formulations were transferred into a vacuum manifold and
      sterile filtered into a rack holding 96 glass vials. The vials were sealed with a
      capmat of individual caps and placed in stability stations. Stability of the
      samples prepared by this process and by the standard process was demonstrated to
      be comparable. This process enabled screening a number of formulations of a
      protein at an early pharmaceutical development stage with a short sample
      preparation time. 

PMID- 25969452
TI  - Endovascular parent artery occlusion of proximal posterior cerebral artery
      aneurysms: a report of two cases.
AB  - We report two cases of proximal posterior cerebral artery (PCA) aneurysms treated
      with endovascular parent artery occlusion (PAO) with coils. In both cases,
      selective injection from the 4 F distal access catheter clearly showed the
      perforating arteries arising from the PCA. Case No 1, a 49-year-old woman, was
      successfully treated with preservation of a paramedian artery. Case No 2, a 54
      year-old woman, was treated in the same manner. The patient underwent extensive
      thalamic infarction after the procedure because of paramedian artery occlusion.
      Endovascular PAO with coils is feasible for proximal PCA aneurysms; however,
      preservation of perforating arteries arising from the PCA is mandatory. 

PMID- 25969453
TI  - An Exploratory Analysis of the Smoking and Physical Activity Outcomes From a
      Pilot Randomized Controlled Trial of an Exercise Assisted Reduction to Stop
      Smoking Intervention in Disadvantaged Groups.
AB  - INTRODUCTION: Economically disadvantaged smokers not intending to stop may
      benefit from interventions aimed at reducing their smoking. This study assessed
      the effects of a behavioral intervention promoting an increase in physical
      activity versus usual care in a pilot randomized controlled trial. METHODS:
      Disadvantaged smokers who wanted to reduce but not quit were randomized to either
      a counseling intervention of up to 12 weeks to support smoking reduction and
      increased physical activity (n = 49) or usual care (n = 50). Data at 16 weeks
      were collected for various smoking and physical activity outcomes. Primary
      analyses consisted of an intention to treat analysis based on complete case data.
      Secondary analyses explored the impact of handling missing data. RESULTS:
      Compared with controls, intervention smokers were more likely to initiate a quit
      attempt (36 vs. 10%; odds ratio 5.05, [95% CI: 1.10; 23.15]), and a greater
      proportion achieved at least 50% reduction in cigarettes smoked (63 vs. 32%; 4.21
      [1.32; 13.39]). Postquit abstinence measured by exhaled carbon monoxide at 4-week
      follow-up showed promising differences between groups (23% vs. 6%; 4.91 [0.80;
      30.24]). No benefit of intervention on physical activity was found. Secondary
      analyses suggested that the standard missing data assumption of "missing" being
      equivalent to "smoking" may be conservative resulting in a reduced intervention
      effect. CONCLUSIONS: A smoking reduction intervention for economically
      disadvantaged smokers which involved personal support to increase physical
      activity appears to be more effective than usual care in achieving reduction and
      may promote cessation. The effect does not appear to be influenced by an increase
      in physical activity.

PMID- 25969454
TI  - Mitochondrial genome evolution in yeasts: an all-encompassing view.
AB  - Mitochondria are important organelles that harbor their own genomes encoding a
      key set of proteins that ensure respiration and provide the eukaryotic cell with
      energy. Recent advances in high-throughput sequencing technologies present a
      unique opportunity to explore mitochondrial (mt) genome evolution. The
      Saccharomycotina yeasts have proven to be the leading organisms for mt
      comparative and population genomics. In fact, the explosion of complete yeast mt
      genome sequences has allowed for a broader view of the mt diversity across this
      incredibly diverse subphylum, both within and between closely related species.
      Here, we summarize the present state of yeast mitogenomics, including the
      currently available data and what it reveals concerning the diversity of content,
      organization, structure and evolution of mt genomes. 

PMID- 25969455
TI  - Development of progressive albuminuria in male Munich Wistar Fromter rats is
      androgen dependent.
AB  - Munich Wistar Fromter (MWF) rats develop spontaneous albuminuria that is linked
      to autosomal genetic loci and inherit a nephron deficit in both female and male
      animals, respectively. However, albuminuria and kidney damage are clearly more
      pronounced in males. Here we tested whether androgens and the androgen receptor
      influence albuminuria in male MWF. We first demonstrated in a pilot study that
      orchiectomy (Ox) of male MWF led to a significant suppression of urinary albumin
      excretion (UAE), while continuous testosterone supplementation in MWF Ox led to
      UAE levels similar to sham-operated (Sham) MWF rats. Subsequently, we performed a
      comparative main study between male MWF and normal Wistar rats to evaluate the
      effect of the androgen receptor on UAE development in adult animals up to the age
      of 18 wk. MWF Sham developed a marked increase in UAE compared with Wistar Sham
      (48.30 +/- 6.16 vs. 0.42 +/- 0.08 mg/24 h, P < 0.0001). UAE was significantly
      lower in MWF Ox compared with MWF Sham (-55%, P < 0.0001). In MWF Ox animals
      supplemented with testosterone and treated with the androgen receptor antagonist
      flutamide (OxTF) UAE at 18 wk was even lower compared with MWF Ox (-71%, P <
      0.01) and similar to age-matched female MWF. The mRNA expression of renal tubular
      injury markers Kim1 and NGAL was increased in MWF Sham compared with Wistar Sham
      (P < 0.0008, respectively) and expression decreased significantly in MWF OxTF (P
      < 0.0004, respectively). Thus, the sexual dimorphism in albuminuria development
      in MWF can be attributed to testosterone and the androgen receptor in male rats.

PMID- 25969456
TI  - Genome-wide gene expression analysis for target genes to differentiate patients
      with intestinal tuberculosis and Crohn's disease and discriminative value of
      FOXP3 mRNA expression.
AB  - BACKGROUND AND AIMS: Crohn's disease (CD) and intestinal tuberculosis (ITB) are
      both chronic granulomatous conditions with similar phenotypic presentations.
      Hence, there is need for a biomarker to differentiate between both these two
      diseases. This study aimed at genome-wide gene expression analysis of colonic
      biopsies from confirmed cases of ITB and CD in comparison with controls. To
      evaluate the role of T regulatory cells, forkhead box P3 (FOXP3) mRNA expression
      was quantified in serum as well as in colonic biopsies from patients with ITB and
      with the controls. METHODS: Paired samples, including serum and colonic biopsies,
      were taken from 33 study subjects (CD, ITB and controls), and total RNA was
      extracted. Human whole genome gene expression microarray analysis was performed
      using the Illumina HumanWG-6 BeadChip Kit with six total RNA samples of the three
      groups in duplicates. Real-time PCR for FOXP3 mRNA expression was analyzed in
      serum samples and colonic biopsy samples (4-CD, 5-ITB, 4-controls). RESULTS: In
      CD and ITB there was 1.5-fold upregulation of 92 and 382 genes and 1.5-fold
      downregulation of 91 and 256 genes, respectively. Peroxisome proliferators via
      the PPARgamma pathway were most significantly downregulated (P < 0.005) in CD.
      Additionally, the IL4/5/6 signaling pathways and Toll-like receptor signaling
      pathway were identified as significantly differentially regulated (P < 0.005) at
      > 2-fold change. In ITB, the complement activation pathway, specifically the
      classical pathway, was the most significantly upregulated. FOXP3 mRNA expression
      was significantly elevated in colonic biopsies obtained from ITB patients as
      compared with CD cases (4.70 +/- 2.21 vs 1.48 +/- 0.31, P = 0.016). CONCLUSIONS:
      FOXP3 mRNA expression in colonic mucosa could be a discriminatory marker between
      ITB and CD. Upregulation of the complement activation pathway in ITB suggests
      that pathogenetic mechanisms for ITB are similar to those of pulmonary
      tuberculosis. In CD, downregulation of PPARgamma was seen in colonic tissue,
      suggesting that restoration of PPARgamma-dependent anti-microbial barrier
      function may be a therapeutic target.

PMID- 25969458
TI  - Retraction for Siddiqui et al., Fine specificity of Plasmodium vivax Duffy
      binding protein binding engagement of the Duffy antigen on human erythrocytes.

PMID- 25969457
TI  - Thoracic perspective revisited in chronic liver disease.
AB  - A variety of chest manifestations are seen in patients with chronic liver
      diseases, namely hepatopulmonary syndrome, portopulmonary hypertension,
      intrathoracic portosystemic collaterals, hepatic hydrothorax, infections, drug
      induced changes, manifestations of hepatocellular carcinoma, gynecomastia, acute
      respiratory distress syndrome, autoimmune changes, aspiration pneumonitis and
      changes due to alpha1-antitrypsin deficiency. Gastroenterologists and
      radiologists should be aware of these entities; knowledge of the imaging findings
      specific to each condition is of prime importance for managing such patients. 

PMID- 25969460
TI  - Maintenance of Quantitative Genetic Variance Under Partial Self-Fertilization,
      with Implications for Evolution of Selfing.
AB  - We analyze two models of the maintenance of quantitative genetic variance in a
      mixed-mating system of self-fertilization and outcrossing. In both models purely
      additive genetic variance is maintained by mutation and recombination under
      stabilizing selection on the phenotype of one or more quantitative characters.
      The Gaussian allele model (GAM) involves a finite number of unlinked loci in an
      infinitely large population, with a normal distribution of allelic effects at
      each locus within lineages selfed for tau consecutive generations since their
      last outcross. The infinitesimal model for partial selfing (IMS) involves an
      infinite number of loci in a large but finite population, with a normal
      distribution of breeding values in lineages of selfing age tau. In both models a
      stable equilibrium genetic variance exists, the outcrossed equilibrium, nearly
      equal to that under random mating, for all selfing rates, r, up to critical
      value, [Formula: see text], the purging threshold, which approximately equals the
      mean fitness under random mating relative to that under complete selfing. In the
      GAM a second stable equilibrium, the purged equilibrium, exists for any positive
      selfing rate, with genetic variance less than or equal to that under pure
      selfing; as r increases above [Formula: see text] the outcrossed equilibrium
      collapses sharply to the purged equilibrium genetic variance. In the IMS a single
      stable equilibrium genetic variance exists at each selfing rate; as r increases
      above [Formula: see text] the equilibrium genetic variance drops sharply and then
      declines gradually to that maintained under complete selfing. The implications
      for evolution of selfing rates, and for adaptive evolution and persistence of
      predominantly selfing species, provide a theoretical basis for the classical view
      of Stebbins that predominant selfing constitutes an "evolutionary dead end."

PMID- 25969461
TI  - MSH3 Promotes Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo.
AB  - Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40
      neurodegenerative and neuromuscular diseases, including myotonic dystrophy and
      Huntington's disease, yet the pathway to expansion remains poorly understood. An
      important step in expansion is the shift from a stable TNR sequence to an
      unstable, expanding tract, which is thought to occur once a TNR attains a
      threshold length. Modeling of human data has indicated that TNR tracts are
      increasingly likely to expand as they increase in size and to do so in increments
      that are smaller than the repeat itself, but this has not been tested
      experimentally. Genetic work has implicated the mismatch repair factor MSH3 in
      promoting expansions. Using Saccharomyces cerevisiae as a model for CAG and CTG
      tract dynamics, we examined individual threshold-length TNR tracts in vivo over
      time in MSH3 and msh3Delta backgrounds. We demonstrate, for the first time, that
      these TNR tracts are highly dynamic. Furthermore, we establish that once such a
      tract has expanded by even a few repeat units, it is significantly more likely to
      expand again. Finally, we show that threshold- length TNR sequences readily
      accumulate net incremental expansions over time through a series of small
      expansion and contraction events. Importantly, the tracts were substantially
      stabilized in the msh3Delta background, with a bias toward contractions,
      indicating that Msh2-Msh3 plays an important role in shifting the expansion
      contraction equilibrium toward expansion in the early stages of TNR tract
      expansion.

PMID- 25969462
TI  - Intratracheal instillation of pravastatin for the treatment of murine allergic
      asthma: a lung-targeted approach to deliver statins.
AB  - Systemic treatment with statins mitigates allergic airway inflammation, TH2
      cytokine production, epithelial mucus production, and airway hyperreactivity
      (AHR) in murine models of asthma. We hypothesized that pravastatin delivered
      intratracheally would be quantifiable in lung tissues using mass spectrometry,
      achieve high drug concentrations in the lung with minimal systemic absorption,
      and mitigate airway inflammation and structural changes induced by ovalbumin.
      Male BALB/c mice were sensitized to ovalbumin (OVA) over 4 weeks, then exposed to
      1% OVA aerosol or filtered air (FA) over 2 weeks. Mice received intratracheal
      instillations of pravastatin before and after each OVA exposure (30 mg/kg). Ultra
      performance liquid chromatography - mass spectrometry was used to quantify
      plasma, lung, and bronchoalveolar lavage fluid (BALF) pravastatin concentration.
      Pravastatin was quantifiable in mouse plasma, lung tissue, and BALF (BALF > lung
      > plasma for OVA and FA groups). At these concentrations pravastatin inhibited
      airway goblet cell hyperplasia/metaplasia, and reduced BALF levels of cytokines
      TNFalpha and KC, but did not reduce BALF total leukocyte or eosinophil cell
      counts. While pravastatin did not mitigate AHR, it did inhibit airway
      hypersensitivity (AHS). In this proof-of-principle study, using novel mass
      spectrometry methods we show that pravastatin is quantifiable in tissues,
      achieves high levels in mouse lungs with minimal systemic absorption, and
      mitigates some pathological features of allergic asthma. Inhaled pravastatin may
      be beneficial for the treatment of asthma by having direct airway effects
      independent of a potent anti-inflammatory effect. Statins with greater
      lipophilicity may achieve better anti-inflammatory effects warranting further
      research. 

PMID- 25969463
TI  - Visualization and quantitation of GLUT4 translocation in human skeletal muscle
      following glucose ingestion and exercise.
AB  - Insulin- and contraction-stimulated increases in glucose uptake into skeletal
      muscle occur in part as a result of the translocation of glucose transporter 4
      (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed
      to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4
      redistribution from intracellular stores to the PM in response to glucose feeding
      and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus
      lateralis of ten insulin-sensitive men in the basal state and following 30 min of
      cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a
      second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the
      basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and
      dystrophin colocalization, measured using the Pearson's correlation coefficient,
      was increased following 30 min of cycling exercise (baseline r = 0.47 +/- 0.01;
      post exercise r = 0.58 +/- 0.02; P < 0.001) and 30 min after glucose ingestion
      (baseline r = 0.42 +/- 0.02; 30 min r = 0.46 +/- 0.02; P < 0.05). Large and small
      GLUT4 clusters were partially depleted following 30 min cycling exercise, but not
      30 min after glucose feeding. This study has, for the first time, used
      immunofluorescence microscopy in human skeletal muscle to quantify increases in
      GLUT4 and dystrophin colocalization and depletion of GLUT4 from large and smaller
      clusters as evidence of net GLUT4 translocation to the PM. 

PMID- 25969464
TI  - High-frequency voltage oscillations in cultured astrocytes.
AB  - Because of their close interaction with neuronal physiology, astrocytes can
      modulate brain function in multiple ways. Here, we demonstrate a yet unknown
      astrocytic phenomenon: Astrocytes cultured on microelectrode arrays (MEAs)
      exhibited extracellular voltage fluctuations in a broad frequency spectrum (100
      600 Hz) after electrical stimulation. These aperiodic high-frequency oscillations
      (HFOs) could last several seconds and did not spread across the MEA. The voltage
      gated calcium channel antagonist cilnidipine dose-dependently decreased the power
      of the oscillations. While intracellular calcium was pivotal, incubation with
      bafilomycin A1 showed that vesicular release of transmitters played only a minor
      role in the emergence of HFOs. Gap junctions and volume-regulated anionic
      channels had just as little functional impact, which was demonstrated by the
      addition of carbenoxolone (100 MUmol/L) and NPPB (100 MUmol/L). Hyperpolarization
      with low potassium in the extracellular solution (2 mmol/L) dramatically raised
      oscillation power. A similar effect was seen when we added extra sodium (+50
      mmol/L) or if we replaced it with NMDG(+) (50 mmol/L). The purinergic receptor
      antagonist PPADS suppressed the oscillation power, while the agonist ATP (100
      MUmol/L) had only an increasing effect when the bath solution pH was slightly
      lowered to pH 7.2. From these observations, we conclude that astrocytic voltage
      oscillations are triggered by activation of voltage-gated calcium channels and
      driven by a downstream influx of cations through channels that are permeable for
      large ions such as NMDG(+). Most likely candidates are subtypes of pore-forming
      P2X channels with a low affinity for ATP. 

PMID- 25969466
TI  - An age-old problem?

PMID- 25969465
TI  - Chronic intermittent psychological stress promotes macrophage reverse cholesterol
      transport by impairing bile acid absorption in mice.
AB  - Psychological stress is a risk factor for atherosclerosis, yet the
      pathophysiological mechanisms involved remain elusive. The transfer of
      cholesterol from macrophage foam cells to liver and feces (the macrophage
      specific reverse cholesterol transport, m-RCT) is an important antiatherogenic
      pathway. Because exposure of mice to physical restraint, a model of psychological
      stress, increases serum levels of corticosterone, and as bile acid homeostasis is
      disrupted in glucocorticoid-treated animals, we investigated if chronic
      intermittent restraint stress would modify m-RCT by altering the enterohepatic
      circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5
      days exhibited increased transit through the large intestine and enhanced fecal
      bile acid excretion. Of the transcription factors and transporters that regulate
      bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X
      receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast
      growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium
      dependent bile acid transporter (ASBT), responsible for active bile acid
      absorption, remained unchanged. Neither did the hepatic expression of cholesterol
      7alpha-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis,
      change in the stressed mice. Evaluation of the functionality of the m-RCT pathway
      revealed increased fecal excretion of bile acids that had been synthesized from
      macrophage-derived cholesterol. Overall, our study reveals that chronic
      intermittent stress in mice accelerates m-RCT specifically by increasing fecal
      excretion of bile acids. This novel mechanism of m-RCT induction could have
      antiatherogenic potential under conditions of chronic stress. 

PMID- 25969468
TI  - Core promoter sequence in yeast is a major determinant of expression level.
AB  - The core promoter is the regulatory sequence to which RNA polymerase is recruited
      and where it acts to initiate transcription. Here, we present the first
      comprehensive study of yeast core promoters, providing massively parallel
      measurements of core promoter activity and of TSS locations and relative usage
      for thousands of native and designed sequences. We found core promoter activity
      to be highly correlated to the activity of the entire promoter and that sequence
      variation in different core promoter regions substantially tunes its activity in
      a predictable way. We also show that location, orientation, and flanking bases
      critically affect TATA element function, that transcription initiation in highly
      active core promoters is focused within a narrow region, that poly(dA:dT)
      orientation has a functional consequence at the 3' end of promoters, and that
      orthologous core promoters across yeast species have conserved activities. Our
      results demonstrate the importance of core promoters in the quantitative study of
      gene regulation. 

PMID- 25969469
TI  - Asymmetry in CT Scan Measures of Thigh Muscle 2 Months After Hip Fracture: The
      Baltimore Hip Studies.
AB  - BACKGROUND: Hip fracture is an important problem for older adults with
      significant functional consequences. After hip fracture, reduced muscle loading
      can result in muscle atrophy. METHODS: We compared thigh muscle characteristics
      in the fractured leg to those in the nonfractured leg in participants from the
      Baltimore Hip Studies 7th cohort using computed tomography scan imaging. RESULTS:
      At 2 months postfracture, a single 10mm axial computed tomography scan was
      obtained at the midthigh level in 43 participants (23 men, 20 women) with a mean
      age of 79.9 years (range: 65-96 years), and thigh muscle cross-sectional area,
      cross-sectional area of intermuscular adipose tissue, and mean radiologic
      attenuation were measured. Total thigh muscle cross-sectional area was less on
      the side of the fracture by 9.46cm(2) (95% CI: 5.97cm(2), 12.95cm(2)) while the
      cross-sectional area of intermuscular adipose tissue was greater by 2.97cm(2)
      (95% CI: 1.94cm(2), 4.01cm(2)) on the fractured side. Mean muscle attenuation was
      lower on the side of the fracture by 3.66 Hounsfield Units (95% CI: 2.98
      Hounsfield Units, 4.34 Hounsfield Units). CONCLUSIONS: The observed asymmetry is
      consistent with the effect of disuse and inflammation in the affected limb along
      with training effects in the unaffected limb due to the favoring of this leg with
      ambulation during the postfracture period.

PMID- 25969470
TI  - Evidence-based guidelines for treating depressive disorders with antidepressants:
      A revision of the 2008 British Association for Psychopharmacology guidelines.
AB  - A revision of the 2008 British Association for Psychopharmacology evidence-based
      guidelines for treating depressive disorders with antidepressants was undertaken
      in order to incorporate new evidence and to update the recommendations where
      appropriate. A consensus meeting involving experts in depressive disorders and
      their management was held in September 2012. Key areas in treating depression
      were reviewed and the strength of evidence and clinical implications were
      considered. The guidelines were then revised after extensive feedback from
      participants and interested parties. A literature review is provided which
      identifies the quality of evidence upon which the recommendations are made. These
      guidelines cover the nature and detection of depressive disorders, acute
      treatment with antidepressant drugs, choice of drug versus alternative treatment,
      practical issues in prescribing and management, next-step treatment, relapse
      prevention, treatment of relapse and stopping treatment. Significant changes
      since the last guidelines were published in 2008 include the availability of new
      antidepressant treatment options, improved evidence supporting certain
      augmentation strategies (drug and non-drug), management of potential long-term
      side effects, updated guidance for prescribing in elderly and adolescent
      populations and updated guidance for optimal prescribing. Suggestions for future
      research priorities are also made. 

PMID- 25969471
TI  - Intraindividual Reaction Time Variability, Falls, and Gait in Old Age: A
      Systematic Review.
AB  - OBJECTIVES: Intraindividual variability (IIV) refers to the variation in reaction
      time (RT) performance across a given cognitive task. As greater IIV may reflect
      compromise of the frontal circuitry implicated in falls and gait impairment in
      older adults, we conducted a systematic review of the literature relating to this
      issue. METHODS: Searches were conducted of electronic databases that identified
      empirical investigations of IIV, falls, and gait in older adult samples with a
      mean age of 65 years or older. Data were extracted relating to IIV measures,
      study population, and outcomes. RESULTS: Of 433 studies initially identified, 9
      met inclusion criteria for IIV and falls (n = 5), and gait (n = 4). Representing
      a total of 2,810 older participants, all of the studies of IIV and falls showed
      that elevated variability was associated with increased risk of falling, and half
      of the studies of gait indicated greater IIV was related to gait impairment.
      DISCUSSION: Across studies, IIV measures were consistently associated with falls
      in older persons and demonstrated some potential in relation to gait. IIV metrics
      may, therefore, have considerable potential in clinical contexts and supplement
      existing test batteries in the assessment of falls risk and gait impairment in
      older populations.

PMID- 25969472
TI  - What's good for the goose is not good for the gander: Age and gender differences
      in scanning emotion faces.
AB  - Objectives: Research indicates that older adults' (>=60 years) emotion
      recognition is worse than that of young adults, young and older men's emotion
      recognition is worse than that of young and older women (respectively), older
      adults' looking at mouths compared with eyes is greater than that of young
      adults. Nevertheless, previous research has not compared older men's and women's
      looking at emotion faces so the present study had two aims: (a) to examine
      whether the tendency to look at mouths is stronger amongst older men compared
      with older women and (b) to examine whether men's mouth looking correlates with
      better emotion recognition. Method: We examined the emotion recognition abilities
      and spontaneous gaze patterns of young (n = 60) and older (n = 58) males and
      females as they labelled emotion faces. Results: Older men spontaneously looked
      more to mouths than older women, and older men's looking at mouths correlated
      with their emotion recognition, whereas women's looking at eyes correlated with
      their emotion recognition. Discussion: The findings are discussed in relation to
      a growing body of research suggesting both age and gender differences in response
      to emotional stimuli and the differential efficacy of mouth and eyes looking for
      men and women.

PMID- 25969473
TI  - Aquimarina agarivorans sp. nov., a genome-sequenced member of the class
      Flavobacteriia isolated from Gelidium amansii.
AB  - A novel Gram-stain-negative, facultatively anaerobic, rod-shaped, agar-digesting
      bacterial strain, designated HQM9T, was isolated from the surface of the marine
      red alga Gelidium amansii collected from the intertidal zone of Weihai, China.
      Cells of HQM9T were 3.0-4.0 MUm long and 0.2-0.3 MUm wide and lacked flagella.
      The new isolate grew optimally at 28-30  degrees C, at pH 7.0-7.5, and in the
      presence of 2.5-3.0% NaCl. The predominant cellular fatty acids were iso-C15 : 0
      and iso-C17 : 0 3-OH. The sole menaquinone was MK-6. The DNA G+C content was 33
      mol%. The major polar lipids were comprised of phosphatidylethanolamine and four
      unknown polar lipids. Based on the 16S rRNA gene sequence, the closest relative
      was Aquimarina agarilytica ZC1T with 97.16% sequence similarity, with which
      strain HQM9T formed a distinct cluster belonging to the genus Aquimarina in a
      phylogenetic tree. Moreover, average nucleotide identity and estimated DNA-DNA
      hybridization values between strains HQM9T and ZC1T were 78.7% and 12.50 +/-
      2.95%, respectively. On the basis of phenotypic, chemotaxonomic and phylogenetic
      analysis, strain HQM9T represents the type strain of a novel species within the
      genus Aquimarina in the family Flavobacteriaceae, phylum Bacteroidetes, for which
      the name Aquimarina agarivorans sp. nov. is proposed. The type strain is HQM9T (
      = ATCC BAA-2612T = CICC 10835T).

PMID- 25969474
TI  - Lutibacter crassostreae sp. nov., isolated from oyster.
AB  - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated, non-gliding
      and ovoid or rod-shaped bacterial strain, designated TYO-8T, was isolated from an
      oyster collected from the South Sea in South Korea. Strain TYO-8T grew optimally
      at 25  degrees C, at pH 7.0-8.0 and in the presence of 2.0-3.0% (w/v) NaCl. A
      neighbour-joining phylogenetic tree, based on 16S rRNA gene sequences, revealed
      that strain TYO-8T fell within the clade comprising the type strains of species
      of the genus Lutibacter, clustering coherently with the type strain of Lutibacter
      litoralis with a sequence similarity of 99.3%. Strain TYO-8T exhibited 16S rRNA
      gene sequence similarity values of 95.3-97.5% to the type strains of other
      species of the genus Lutibacter and of less than 92.9% to the type strains of
      other species with validly published names. Strain TYO-8T contained MK-6 as the
      predominant menaquinone and iso-C15 : 0, iso-C15 : 0 3-OH and iso-C15 : 1 G as
      the major fatty acids. The major polar lipids of strain TYO-8T were
      phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of
      strain TYO-8T was 33.8 mol% and its DNA-DNA relatedness values with the type
      strains of L. litoralis, Lutibacter aestuarii and Lutibacter flavus were 13-27%.
      The differential phenotypic properties, together with the phylogenetic and
      genetic distinctiveness, revealed that strain TYO-8T is distinct from other
      species of the genus Lutibacter. On the basis of the data presented, strain TYO
      8T is considered to represent a novel species of the genus Lutibacter, for which
      the name Lutibacter crassostreae sp. nov. is proposed. The type strain is TYO-8T
      ( = KCTC 42461T = NBRC 110923T).

PMID- 25969475
TI  - Lacinutrix undariae sp. nov., isolated from a brown algae reservoir.
AB  - A Gram-stain-negative, aerobic, non-flagellated, non-gliding and ovoid or rod
      shaped bacterium, designated strain W-BA8T, was isolated from a brown algae
      reservoir on the South Sea, South Korea, and subjected to a polyphasic taxonomic
      approach. Strain W-BA8T grew optimally at 25  degrees C, at pH 7.0-7.5 and in the
      presence of 1.0-2.0% (w/v) NaCl. Neighbour-joining and maximum-parsimony
      phylogenetic trees based on 16S rRNA gene sequences showed that strain W-BA8T
      clustered with the type strains of species of the genus Lacinutrix. Strain W-BA8T
      exhibited 16S rRNA gene sequence similarity values of 94.9-96.5% to the type
      strains of Lacinutrix species and of less than 95.8% to the type strains of other
      recognized species. Strain W-BA8T contained MK-6 as the predominant menaquinone
      and iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH as major
      fatty acids. The polar lipid profile of strain W-BA8T contained
      phosphatidylethanolamine, two unidentified lipids and one unidentified glycolipid
      as major components. The DNA G+C content of strain W-BA8T was 35 mol%.
      Differential phenotypic properties, together with phylogenetic distinctiveness,
      revealed that strain W-BA8T is separated from other species of the genus
      Lacinutrix. On the basis of the data presented, strain W-BA8T is considered to
      represent a novel species of the genus Lacinutrix, for which the name Lacinutrix
      undariae sp. nov. is proposed. The type strain is W-BA8T ( = KCTC 42176T = CECT
      8671T).

PMID- 25969476
TI  - Flavobacterium procerum sp. nov., isolated from freshwater.
AB  - A Gram-reaction-negative, strictly aerobic, yellow-pigmented, rod-shaped
      bacterium, designated strain T3T, was isolated from freshwater of Chishui River
      flowing through Maotai town, Guizhou, south-west China. Analysis of the16S rRNA
      gene sequence indicated that strain T3T was a member of the genus Flavobacterium
      and closely related to Flavobacterium resistens DSM 19382T (96.8 %). The novel
      strain was able to grow at 10-34  degrees C (optimum 28  degrees C), pH 6.0-11.0
      (optimum pH 8.0-9.0) and with 0-2.0 % (w/v) NaCl (optimum 0 %). The major polar
      lipids were phosphatidylethanolamine, two unknown glycolipids, five unknown
      aminolipids and four unidentified lipids, and the major respiratory quinone was
      MK-6. The predominant fatty acids were C16  :  1omega7c and/or C16  :  1omega6c
      and iso-C15  :  0. The DNA G+C content of the strain was 36 mol  %. Based on
      these data, strain T3T represents a novel species of the genus Flavobacterium,
      for which the name Flavobacterium procerum sp. nov. is proposed. The type strain
      is T3T ( = CGMCC 1.12926T = JCM 30113T).

PMID- 25969480
TI  - Emergency surgery for intestinal obstruction revealing ileal Crohn's disease (CD)
      during pregnancy.
AB  - Few data are available regarding emergency surgery for Crohn's disease (CD)
      during pregnancy. A 22-year -old woman, at 26 weeks of pregnancy, was admitted
      for premature labour, intestinal obstruction and systemic inflammation. Biology
      and ultrasonography were not helpful; imaging was completed with a CT scan, which
      confirmed the mechanical ileal obstruction. The intestinal obstruction worsened
      and led to emergency surgery. An inflammatory stenosis of the terminal ileum with
      two fistulas was found. An ileal resection and ileostomy were performed. The
      pathological analysis of the resected specimen confirmed CD. The postoperative
      course was uneventful. The delivery of a baby with normal weight and status
      occurred at term (40 weeks of amenorrhoea). There have been only 10 case reports
      of intestinal complications revealing CD during pregnancy. The delay in diagnosis
      and adequate treatment led to significant maternal and fetal morbidity and
      mortality. This case suggests that intestinal surgery for CD is feasible during
      pregnancy and may be associated with a favourable outcome for the baby as well as
      for the mother.

PMID- 25969481
TI  - Non-puerperal uterine inversion in a patient with intracranial sigmoid sinus
      thrombosis and facial palsy.
AB  - Non-puerperal uterine inversion and cranial nerve palsies in patients with
      sigmoid sinus thrombosis are both extremely rare. We report a case of a patient
      who presented with both simultaneously. The symptoms of sigmoid sinus thrombosis
      resolved with subcutaneous enoxaparin, and an abdominal dissection with removal
      of the uterus vaginally resulted in a successful outcome for the patient. 

PMID- 25969482
TI  - Calcium maelstrom: recalcitrant hypocalcaemia following rapid correction of
      thyrotoxicosis, exacerbated by pregnancy.
AB  - A 29-year-old pregnant woman with Graves' disease presented with severe
      persistent hypocalcaemia after thyroidectomy. Six months prior to presentation
      she was diagnosed with Graves' disease and remained uncontrolled with
      methimazole. She was confirmed pregnant prior to radioactive iodine ablation
      (RAI), and underwent total thyroidectomy during her second trimester. After
      surgery, continuous intravenous calcium infusion was required until delivery of
      the fetus allowed discontinuation at postoperative day 18, despite oral calcium
      and calcitriol administration. A total of 38 g of oral and 7.5 g of intravenous
      elemental calcium was administered. We report an unusual case of recalcitrant
      hypocalcaemia thought to be due to a combination of postoperative
      hypoparathyroidism, combined with thyrotoxic osteodystrophy and pregnancy, after
      surgical correction of Graves' disease. Increased vigilance and early calcium
      supplementation should be a priority in the management of these patients.

PMID- 25969483
TI  - Preservation of fertility in non-Peutz-Jegher syndrome-associated ovarian sex
      cord tumour with annular tubules.
AB  - We report the successful conservative management of a non-Peutz-Jegher syndrome
      associated ovarian sex cord tumour with annular tubules in a 32-year-old patient.
      The patient underwent a unilateral salpingo-oophorectomy by laparoscopy, and
      conceived spontaneously approximately 6 months after the diagnosis. After a
      normal term pregnancy, she underwent a contralateral laparoscopic salpingo
      oophorectomy with hysterectomy. The patient is now on hormone replacement therapy
      and, after 30 months of follow-up, continues to present no sign of disease
      recurrence.

PMID- 25969484
TI  - Lessons from two cases: is Fabry disease the correct diagnosis?
AB  - Fabry disease (FD) is an X linked inherited lysosomal storage disorder with
      complex multisystem involvement; it is caused by deficiency of the lysosomal
      enzyme alpha-galactosidase. Deficient enzyme activity leads to a wide spectrum of
      clinical manifestations consisting of dermatological, ophthalmological,
      cardiovascular, and urinary and central nervous system findings. As a result, FD
      should be considered in the differential diagnosis of many systemic diseases.
      Diagnosis of FD can arise from careful clinical and instrumental investigations,
      together with family history data and accurate interpretation of genetic and
      enzymatic analyses. Lack of knowledge on clinical findings of the disease and
      inept investigation methods unfortunately result in erroneous diagnosis. We
      present two patients who were referred to our clinic with a suspicion of ED and
      finally diagnosed as glycogen storage disorder type III and ornithine
      transcarbamylase deficiency, respectively. 

PMID- 25969485
TI  - Intermediate uveitis: an unusual presentation of cytomegalovirus intraocular
      infection in an immunocompetent patient.
AB  - We report a case of cytomegalovirus (CMV) intraocular infection in an otherwise
      healthy 51-year-old patient, presenting atypically as isolated intermediate
      uveitis without retinitis or retinal vasculitis. The patient had a confirmed CMV
      infection as a cause of her intraocular inflammation via PCR DNA testing of an
      aqueous sample. Appropriate oral antiviral therapy was initiated, and resulted in
      complete resolution of inflammation and improvement in visual acuity.
      Prophylactic therapy was instituted thereafter. 

PMID- 25969486
TI  - High-flow priapism following perineal trauma in a child.
AB  - Priapism is a rare condition in children and can be classified as high or low
      flow. We present a case of traumatic high-flow priapism that was successfully
      managed by selective embolisation of a branch of the internal pudendal artery.
      The pertinent clinical features are antecedent trauma and prolonged painless
      partial erection. The investigation of choice is Doppler ultrasound. Management
      can either be conservative, radiological or surgical. While conservative
      management can be safely attempted for 6 weeks, given the nature of the
      condition, early intervention is often required. Radiological embolisation is the
      first line and is successful in 97% of cases. Surgery carries a higher morbidity
      and is only reserved in cases where repeated embolisation has failed. This case
      highlights the importance of a thorough history and careful interpretation of
      imaging with protocolised follow-up of patients by a paediatric urologist for
      early and accurate diagnosis of erectile dysfunction and prompt intervention to
      prevent future complications.

PMID- 25969487
TI  - Successful treatment of a patient with severe atopic dermatitis and severe asthma
      by centrifugal therapeutic plasma exchange.
AB  - This is a case of a 42-year-old atopic man with severe atopic dermatitis and
      asthma who despite long-term immunosuppression was not well controlled. He had a
      very high IgE at 7897 Iu/mL prior to treatment. He underwent two therapeutic
      plasma exchanges (TPEs) through two peripheral lines in our outpatient
      department, which led to an absolute decrease of 44.1% and 37% in his plasma IgE
      for each exchange, and immediate sustained improvement in shortness of breath,
      and atopic dermatitis, and hence led to a vast improvement in his quality of
      life. TPE offers a new exciting adjunctive treatment option for severe atopic
      individuals, where it may provide a novel role to reduce health burden and
      improve clinical symptoms. Further studies need to be performed to establish an
      optimal protocol and potential maintenance with recently available targeted anti
      IgE biologics.

PMID- 25969488
TI  - Pagetoid polyostotic fibrous dysplasia.
AB  - Fibrous dysplasia (FD) is a benign skeletal lesion occurring due to mutation of
      Gs alpha gene and involves one or multiple bones. We present a case of a 30-year
      old female patient, with a 1-year history of swelling under her right eye that
      had gradually increased in size. Extraoral examination revealed a diffuse
      swelling extending anteroposteriorly from preauricular region to nasolabial fold,
      frontonasal region and superoinferiorly from zygoma to body of mandible, causing
      ipsilateral proptosis and contralateral deviation of nose. Intraoral examination
      showed obliteration of right upper and lower buccal vestibule. CT disclosed
      expansile lytic lesions involving multiple skull bones, jaws, sternum, rib and
      thoracic vertebrae. Histopathology displayed broad and interconnected trabeculae
      connected to the host bone exhibiting reversal lines resembling the mosaic
      pattern of Paget's disease. These features suggested pagetoid polyostotic FD. The
      patient underwent cosmetic recontouring and is under regular follow-up
      postoperatively. 

PMID- 25969489
TI  - Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery
      dissection: is early surgical exploration warranted?
AB  - The natural history of spontaneous cerebral artery dissection and thrombosis
      remains uncertain. Concurrent subarachnoid hemorrhage further complicates the
      therapeutic approach. Thus the best strategy for managing patients with acute
      vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we
      present a case of spontaneous posterior inferior cerebellar artery dissection
      presenting with subarachnoid hemorrhage and acute thrombosis. Although the
      patient was initially managed conservatively, angiographic follow-up demonstrated
      recanalization of the diseased vessel, necessitating definitive treatment. Thus
      we propose that angiographic follow-up is necessary in the management of patients
      with subarachnoid hemorrhage in association with apparent vessel thrombosis. 

PMID- 25969490
TI  - Diffuse large B-cell lymphoma causing acute liver failure: a rare case of
      survival.
AB  - Acute liver failure is a rare but life-threatening illness with an incidence of 2
      8 per million population. The most common causes of acute liver failure include
      drug ingestion and viral hepatitis followed by ischaemic hepatocellular injury
      and, less commonly, malignancy. Our patient presented with acute liver failure,
      which was found to be secondary to hepatic infiltration by diffuse large B-cell
      lymphoma. He received early treatment and has been in remission for more than a
      year after his initial presentation. To the best of our knowledge, our patient is
      the second reported survivor of acute liver failure caused by malignant hepatic
      infiltration by diffuse large B-cell lymphoma. 

PMID- 25969491
TI  - Intrahepatic bile duct dilation and gallbladder hydrops due to a cystic duct
      stenosis in a 2-month-old boy.

PMID- 25969492
TI  - Severe acute pancreatitis after EUS-FNA of a pancreatic cyst: a rare, but serious
      complication.
AB  - As a consequence of improved quality of abdominal imaging techniques in the last
      decades, discovery of pancreatic cystic lesions has become more common. The
      clinical significance of these lesions is often unclear and poses a diagnostic
      dilemma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a
      subject of debate regarding its role in the diagnostic evaluation of pancreatic
      masses and cysts. Although risks associated with the procedure are low,
      consequences can be serious and even life-threatening. We report a case of a
      previously healthy 59-year-old woman who suffered severe acute pancreatitis after
      EUS-FNA of a pancreatic cyst, requiring admission to the intensive care unit
      (ICU). Development of infected pancreatic necrosis and, successively, bowel
      ischaemia, led to multiple organ failure. Despite maximal antibiotic and surgical
      treatment the patient succumbed to refractory septic shock. The fatal outcome of
      this case illustrates the importance of balanced decision-making in the
      diagnostic approach of pancreatic cystic lesions. 

PMID- 25969493
TI  - A large mesenteric paraganglioma with lymphovascular invasion.
AB  - Mesenteric paraganglioma is a rare tumour with only 17 known published case
      reports so far. This is the second case that demonstrates lymphovascular invasion
      of the tumour and the third that exhibits its malignant potential. We present a
      case of a 69-year-old woman with a large palpable abdominal mass that was thought
      to arise from the ovary following a staging CT scan. Intraoperatively, a large
      ovoid mass measuring 18 cm*15 cm *11.5 cm was found on the small bowel mesentery.
      Histological examination revealed the characteristic Zellbalen pattern with
      lymphovascular involvement. Mesenteric paraganglioma is rare and remains a
      diagnostic dilemma. Although the majority of paragangliomas are non-functional
      and do not show any malignant potential, individual case-based management is
      needed in view of their unpredictable nature. A multidisciplinary approach with
      genetic counselling and long-term follow-up are usually necessary to monitor for
      future disease recurrence.

PMID- 25969494
TI  - More than a headache: a case of cetuximab-induced aseptic meningitis.
AB  - While the wide belief is that monoclonal antibodies, due to their large size,
      would not be able to penetrate the blood-brain barrier, we present a rare case of
      aseptic meningitis induced by intravenous cetuximab administration. A 58-year-old
      man with tonsillar squamous cell cancer presented with headache and fever, which
      started approximately 1 h after his first dose of cetuximab (loading dose of 400
      mg/m(2) equalling 800 mg). CT scan of the head was non-revealing and laboratory
      tests including complete blood count, serum comprehensive metabolic panel and
      coagulation profile were within normal limits. Aseptic meningitis in the setting
      of cetuximab therapy has been reported on 6 previous occasions. Consistent with
      these prior reports, it is interesting to note that this case also occurred after
      administration of the initial higher loading dose of Cetuximab. This is of
      interest as Cetuximab is more frequently being dosed at 500 mg/m(2) (higher dose)
      every 2 weeks in colorectal cancer.

PMID- 25969495
TI  - Giant hydatid cyst of the pelvis, femur and retroperitoneal space: surgical
      treatment with extended hemipelvectomy.
AB  - Hydatid disease of the bone is a very rare manifestation of the disease, and is
      often associated with debilitating symptoms. We present a rare case of skeletal
      hydatidosis in a 56-year-old man who had been misdiagnosed for many years.
      Massive involvement of the pelvic bones and soft tissues was evident. An extended
      hemipelvectomy was performed in order to achieve resection of the affected
      segments with a clear surgical margin. The patient recovered uneventfully and
      there are no signs of recurrence of the disease. 

PMID- 25969496
TI  - Unusual complication and mechanical murmur following mitral valve clip insertion
      in a patient with a CRT-D.

PMID- 25969497
TI  - The difficulty in diagnosing X linked adrenoleucodystrophy and the importance of
      identifying cerebral involvement.
AB  - Two patients are described, a mother and son, who were initially clinically
      diagnosed with hereditary spastic paraparesis. This was rectified after very long
      chain fatty acid testing confirmed adrenomyeloneuropathy (AMN). The son's initial
      symptoms were characteristic of AMN (the commonest phenotype) but progressed to
      show symptoms of cerebral involvement. This evolution from non-cerebral to
      cerebral AMN is recognised in the medical literature and is increasingly
      important to consider in light of the availability of potential treatments such
      as haematopoietic stem cell transplantation. 

PMID- 25969498
TI  - Atrial myxoma: a rare but well-described cause of increased erythrocyte
      sedimentation rate and anaemia.
AB  - A 56-year-old woman visited her general practitioner 12 months prior with eczema.
      Blood samples showed anaemia, a haemoglobin level of 105 g/L and a high
      erythrocyte sedimentation rate (ESR) of 80 mm. Her eczema was diagnosed as
      discoid lupus erythaematosus but there were no signs of systemic lupus
      erythaematosus. Extensive investigations were made including testing of serial
      blood samples, repeated examinations by specialists in dermatology, rheumatology
      and gynaecology, and several X-rays including CT of the chest and the abdomen,
      all without finding a reasonable underlying diagnosis. One year later, the
      patient presented with dyspnoea associated with effort and body position; she was
      sent for echocardiography, which showed an atrial myxoma filling almost the whole
      left atrium and affecting the mitral valve. She was treated with urgent surgical
      removal and now, 6 weeks postsurgery, has fully recovered. She no longer has
      dyspnoea, her haemoglobin level and ESR have normalised, and the eczema has
      almost disappeared.

PMID- 25969499
TI  - A perianal presentation of myeloid sarcoma.
AB  - Myeloid sarcoma is a rare tumour associated with acute myeloid leucaemia (AML).
      Infrequently, it can occur in myelodysplastic/myeloproliferative overlap syndrome
      conditions such as chronic monomyelocytic leucaemia (CMML), where it often
      heralds the transformation towards an AML. We discuss a rare presentation of
      myeloid sarcoma in the perianal region of a 51-year-old man, who was seen by
      various clinicians and treated for haemorrhoids and perianal abscess. There were
      no gross abnormalities in initial haematological investigations and the patient
      was systemically well. A histological biopsy demonstrated myeloid sarcoma and
      bone marrow aspirate, and trephine confirmed CMML transforming to AML. Treatment
      of myeloid sarcoma is dependent on whether there is associated AML in the bone
      marrow. Dual chemotherapy with cytarabine and daunorubicin remains the gold
      standard treatment in these patients. Sending histology samples of atypical
      lesions when performing incision and drainage procedures is extremely important,
      as it contributes to early detection of rare and malignant tissue diagnoses. 

PMID- 25969500
TI  - Postoperative cystoid macular oedema in a patient on fingolimod.
AB  - We describe the first case of fingolimod-associated bilateral cystoid macular
      oedema (CMO) following uncomplicated cataract surgery. A 57-year-old woman has
      been on fingolimod for the past 2 years for the treatment of relapsing-remitting
      multiple sclerosis. She underwent uneventful consecutive cataract surgery 2 weeks
      apart. Three weeks following the second cataract operation, she reported gradual
      onset blurred vision bilaterally. Examination revealed mildly reduced visual
      acuity and bilateral CMO. Treatment with topical corticosteroids and non
      steroidal anti-inflammatory eye drops, as well as cessation of fingolimod in
      collaboration with the neurologist, resulted in complete resolution of the CMO.
      Patients on fingolimod are likely to be at increased risk of developing
      postoperative CMO.

PMID- 25969501
TI  - Extreme protraction for low-grade gliomas: theoretical proof of concept of a
      novel therapeutical strategy.
AB  - Grade II gliomas are slowly growing primary brain tumours that affect mostly
      young patients and become fatal after a variable time period. Current clinical
      handling includes surgery as first-line treatment. Cytotoxic therapies
      (radiotherapy RT or chemotherapy QT) are used initially only for patients having
      a bad prognosis. Therapies are administered following the 'maximum dose in
      minimum time' principle, which is the same schedule used for high-grade brain
      tumours. Using mathematical models describing the growth of these tumours in
      response to radiotherapy, we find that an extreme protraction therapeutical
      strategy, i.e. enlarging substantially the time interval between RT fractions,
      may lead to better tumour control. Explicit formulas are found providing the
      optimal spacing between doses in a very good agreement with the simulations of
      the full 3D mathematical model approximating the tumour spatiotemporal dynamics.
      This idea, although breaking the well-established paradigm, has biological
      meaning since, in these slowly growing tumours, it may be more favourable to
      treat the tumour as the tumour cells leave the quiescent compartment and move
      into the cell cycle.

PMID- 25969502
TI  - Jinneography: Post-Soviet passages of traumatic exemplarity.
AB  - While Russia has historically and geographically close ties with Islam, the
      second most-practiced religion in its vast territories, the collapse of the USSR
      changed the terms of this relationship in significant ways. One key shift is the
      emergence of new immigration patterns between Russia and former Soviet states.
      Traversing distant lands from the peripheries of the Caucasus and Central Asia to
      mainland Russia in search of work, migrants have come to recognize each other as
      fellow Muslims dispersed in a theological geography on the ruins of the universal
      comradeship dreamed by the Soviet utopia. I propose to study the Islamic
      pedagogical practice of ibra in the context of sociohistorical dynamics of
      education and migration between Russia and Central Asia to further locate and
      analyze this shift in relation to current debates on post-Soviet subjectivity. By
      discussing the case of a spirit possession of a Tajik national performed in
      Russia, I argue that the collective participation in the session pedagogically
      invokes, ciphers, and extends the post-Soviet terrains of history as ibra, or
      exemplary passage of worldly events. To do so, I first locate the Quranic concept
      of ibra as a pedagogical paradigm in Islamic traditions as well as an
      ethnographic lens in the context of educational campaigns for the Muslims of
      Eurasia and then apply the concept to my analysis of the possession session in
      order to show that in the ritualistic incarnations of ghosts, or jinns, the civil
      war of Tajikistan and its continuing cycle of terror is ciphered into a desire
      for learning, as well as a focus on approximation to the divine. 

PMID- 25969504
TI  - Onset of impaired sleep as a predictor of change in health-related behaviours;
      analysing observational data as a series of non-randomized pseudo-trials.
AB  - BACKGROUND: Changes in health-related behaviour may be a key mechanism linking
      impaired sleep to poor health, but evidence on this is limited. In this study, we
      analysed observational data to determine whether onset of impaired sleep is
      followed by changes in health-related behaviours. METHODS: We used data from
      37,508 adults from the longitudinal Finnish Public Sector Study. In analysis of
      59 152 person-observations on duration and quality of sleep and health-related
      behaviours (alcohol consumption, smoking, physical activity and weight control),
      data were treated as a series of non-randomized pseudo-trials with strict
      predefined criteria for data inclusion and temporality. RESULTS: Smokers who
      experienced onset of short sleep were less likely to quit smoking than those with
      persistent normal sleep [odds ratio (OR) = 0.78, 95% confidence interval (CI):
      0.64-0.97]. Onset of short sleep also predicted initiating high-risk alcohol
      consumption (OR = 1.17, 95% CI: 1.00-1.37). Onset of disturbed sleep was
      associated with changes in all assessed health-related behaviours: initiation of
      high-risk alcohol consumption (OR = 1.23, 95% CI: 1.05-1.45), quitting smoking
      (OR = 0.80, 95% CI: 0.63-1.00), becoming physically inactive (OR = 1.17, 95% CI:
      1.06-1.30) and becoming overweight or obese (OR = 1.12, 95% CI: 1.01-1.23).
      CONCLUSIONS: Findings suggest that the onset of short or disturbed sleep are risk
      factors for adverse changes in health-related behaviours. These findings
      highlight potential pathways linking impaired sleep to the development of
      lifestyle-related morbidity and mortality.

PMID- 25969503
TI  - Understanding of research, genetics and genetic research in a rapid ethical
      assessment in north west Cameroon.
AB  - BACKGROUND: There is limited assessment of whether research participants in low
      income settings are afforded a full understanding of the meaning of medical
      research. There may also be particular issues with the understanding of genetic
      research. We used a rapid ethical assessment methodology to explore perceptions
      surrounding the meaning of research, genetics and genetic research in north west
      Cameroon. METHODS: Eleven focus group discussions (including 107 adults) and 72
      in-depth interviews were conducted with various stakeholders in two health
      districts in north west Cameroon between February and April 2012. RESULTS: Most
      participants appreciated the role of research in generating knowledge and
      identified a difference between research and healthcare but gave varied
      explanations as to this difference. Most participants' understanding of genetics
      was limited to concepts of hereditary, with potential benefits limited to the
      level of the individual or family. Explanations based on supernatural beliefs
      were identified as a special issue but participants tended not to identify any
      other special risks with genetic research. CONCLUSION: We demonstrated a variable
      level of understanding of research, genetics and genetic research, with
      implications for those carrying out genetic research in this and other low
      resource settings. Our study highlights the utility of rapid ethical assessment
      prior to complex or sensitive research.

PMID- 25969505
TI  - Transient and sustained effects of child-care attendance on hospital admission
      for gastroenteritis.
AB  - BACKGROUND: There is evidence that children experience a transient increase in
      mild episodes of gastroenteritis when they start attending out-of-home child
      care. We assessed the transient and sustained effects of cumulative day-care
      attendance, age at first enrolment and type of child care facility attended on
      hospitalization rates for gastroenteritis. METHODS: Cox proportional hazard
      models were used to estimate the risk of being hospitalized for gastroenteritis
      in two large cohorts of preschool (<6 years old) and elementary school-going (6
      10 years old) children in Denmark. Day-by-day child-level registry data were
      used. Together, the two cohorts comprised 443,872 children, 21,038
      hospitalizations and 1742,284 child-years (1994-2011). RESULTS: From first day
      care attendance until 12 months of cumulated attendance, preschool children
      attending day-care centres, but not those attending day-care homes, had an
      increased risk of hospitalization for gastroenteritis compared with children
      never attending registered day-care. Such increased risk was highest shortly
      after starting day-care attendance and then gradually declined. After 12 months
      of attendance, attending either day-care centres or day-care homes was associated
      with a lower risk for hospitalization. Such decreased risk was confined to
      children starting day-care attendance before the age of one year and extended
      throughout, but not beyond, their preschool years. CONCLUSIONS: Attending day
      care centres is associated with a higher risk for gastroenteritis hospitalization
      until completing 1 year of attendance. However, if children start attending day
      care before the age of 1 year, they experience a lower risk of being hospitalized
      during their preschool years. This apparent protective effect does not last into
      the elementary school years.

PMID- 25969508
TI  - Correction for Jacques et al., Differentiation of antiinflammatory and
      antitumorigenic properties of stabilized enantiomers of thalidomide analogs.

PMID- 25969506
TI  - Breast Cancer Mortality in African-American and Non-Hispanic White Women by
      Molecular Subtype and Stage at Diagnosis: A Population-Based Study.
AB  - BACKGROUND: Higher breast cancer mortality rates for African-American than non
      Hispanic White women are well documented; however, it remains uncertain if this
      disparity occurs in disease subgroups defined by tumor molecular markers and
      stage at diagnosis. We examined racial differences in outcome according to
      subtype and stage in a diverse, population-based series of 103,498 patients.
      METHODS: We obtained data for all invasive breast cancers diagnosed between
      January 1, 2005, and December 31, 2012, and followed through December 31, 2012,
      among 93,760 non-Hispanic White and 9,738 African-American women in California.
      Molecular subtypes were categorized according to tumor expression of hormone
      receptor (HR, based on estrogen and progesterone receptors) and human epidermal
      growth factor receptor 2 (HER2). Cox proportional hazards models were used to
      calculate relative hazard (RH) and 95% confidence intervals (CI) for breast
      cancer-specific mortality. RESULTS: After adjustment for patient, tumor, and
      treatment characteristics, outcomes were comparable by race for stage I or IV
      cancer regardless of subtype, and HR(+)/HER2(+) or HR(-)/HER2(+) cancer
      regardless of stage. We found substantially higher hazards of breast cancer death
      among African-American women with stage II/III HR(+)/HER2(-) (RH, 1.31; 95% CI,
      1.03-1.65; and RH, 1.39; 95% CI, 1.10-1.75, respectively) and stage III triple
      negative cancers relative to Whites. CONCLUSIONS: There are substantial
      racial/ethnic disparities among patients with stages II/III HR(+)/HER2(-) and
      stage III triple-negative breast cancers but not for other subtype and stage.
      IMPACT: These data provide insights to assess barriers to targeted treatment
      (e.g., trastuzumab or endocrine therapy) of particular subtypes of breast cancer
      among African-American patients.

PMID- 25969509
TI  - Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial
      quality control using a ubiquitin replacement strategy.
AB  - The PTEN-induced putative kinase protein 1 (PINK1) and ubiquitin (UB) ligase
      PARKIN direct damaged mitochondria for mitophagy. PINK1 promotes PARKIN
      recruitment to the mitochondrial outer membrane (MOM) for ubiquitylation of MOM
      proteins with canonical and noncanonical UB chains. PINK1 phosphorylates both
      Ser65 (S65) in the UB-like domain of PARKIN and the conserved Ser in UB itself,
      but the temporal sequence and relative importance of these events during PARKIN
      activation and mitochondria quality control remain poorly understood. Using
      "UB(S65A)-replacement," we find that PARKIN phosphorylation and activation, and
      ubiquitylation of Lys residues on a cohort of MOM proteins, occur similarly
      irrespective of the ability of the UB-replacement to be phosphorylated on S65. In
      contrast, polyubiquitin (poly-UB) chain synthesis, PARKIN retention on the MOM,
      and mitophagy are reduced in UB(S65A)-replacement cells. Analogous experiments
      examining roles of individual UB chain linkage types revealed the importance of
      K6 and K63 chain linkages in mitophagy, but phosphorylation of K63 chains by
      PINK1 did not enhance binding to candidate mitophagy receptors optineurin (OPTN),
      sequestosome-1 (p62), and nuclear dot protein 52 (NDP52) in vitro. Parallel
      reaction monitoring proteomics of total mitochondria revealed the absence of p
      S65-UB when PARKIN cannot build UB chains, and <0.16% of the monomeric UB pool
      underwent S65 phosphorylation upon mitochondrial damage. Combining p-S65-UB and p
      S65-PARKIN in vitro showed accelerated transfer of nonphosphorylated UB to PARKIN
      itself, its substrate mitochondrial Rho GTPase (MIRO), and UB. Our data further
      define a feed-forward mitochondrial ubiquitylation pathway involving PARKIN
      activation upon phosphorylation, UB chain synthesis on the MOM, UB chain
      phosphorylation, and further PARKIN recruitment and enzymatic amplification via
      binding to phosphorylated UB chains. 

PMID- 25969510
TI  - Vernon Mountcastle: Father of neuroscience.

PMID- 25969511
TI  - Designing a mutant CCL2-HSA chimera with high glycosaminoglycan-binding affinity
      and selectivity.
AB  - Chemokines like CCL2 mediate leukocyte migration to inflammatory sites by binding
      to G-protein coupled receptors on the target cell as well as to
      glycosaminoglycans (GAGs) on the endothelium of the inflamed tissue. We have
      recently shown that the dominant-negative Met-CCL2 mutant Y13A/S21K/Q23R with
      improved GAG binding affinity is highly bio-active in several animal models of
      inflammatory diseases. For chronic indications, we have performed here a fusion
      to human serum albumin (HSA) in order to extend the serum half-life of the
      chemokine mutant. To compensate a potential drop in GAG-binding affinity due to
      steric hindrance by HSA, a series of novel CCL2 mutants was generated with
      additional basic amino acids which were genetically introduced at sites oriented
      towards the GAG ligand. From this set of mutants, the Met-CCL2 variant
      Y13A/N17K/S21K/Q23K/S34K exhibited high GAG-binding affinity and a similar
      selectivity as wild type (wt) CCL2. From a set of different HSA-chemokine
      chimeric constructs, the linked HSA(C34A)(Gly)4Ser-Met
      CCL2(Y13A/N17K/S21K/Q23K/S34K) fusion protein was found to show the best overall
      GAG-binding characteristics. Molecular modeling demonstrated an energetically
      beneficial fold of this novel protein chimera. This was experimentally supported
      by GdmCl-induced unfolding studies, in which the fusion construct exhibited a
      well-defined secondary structure and a transition point significantly higher than
      both the wt and the unfused CCL2 mutant protein. Unlike the wt chemokine, the
      quaternary structure of the HSA-fusion protein is monomeric according to size
      exclusion chromatography experiments. In competition experiments, the HSA-fusion
      construct displaced only two of seven unrelated chemokines from heparan sulfate,
      whereas the unfused CCL2 mutant protein displaced five other chemokines. The most
      effective concentration of the HSA-fusion protein in inhibiting CCL2-mediated
      monocyte attachment to endothelial cells, as detected in the flow chamber, was
      8.6 ug/ml. This novel HSA-fusion protein exhibits not only high affinity but also
      selective displacement of chemokines from GAGs binding. HSA is therefore proposed
      to be a highly promising scaffold candidate for therapeutic, GAG-targeting
      chemokine mutants. 

PMID- 25969512
TI  - Back to basics: checklists in aviation and healthcare.

PMID- 25969513
TI  - Effect of Tidal Volume and Nebulizer Type and Position on Albuterol Delivery in a
      Pediatric Model of Mechanical Ventilation.
AB  - BACKGROUND: Optimization of factors affecting aerosol delivery during mechanical
      ventilation in the pediatric population is important. We hypothesized that
      increasing the tidal volume (V(T)), using a vibrating mesh nebulizer, and placing
      the nebulizer at the ventilator would increase lung dose/delivery efficiency.
      METHODS: Continuous-output jet and vibrating mesh nebulizers loaded with
      albuterol (2.5 mg/3 mL) were compared when placed before the Y-piece and at the
      ventilator. The model consisted of a ventilator operated in pressure-regulated
      volume control ventilation mode at a breathing frequency of 20 breaths/min, PEEP
      of 5 cm H2O, FIO2 of 0.4, inspiratory time of 0.75 s, and bias flow of 0.5 L/min
      with a humidifier (37 +/- 1.5 degrees C) and an adult heated-wired circuit. V(T)
      values of 100, 150, 200, and 300 mL were studied. The circuit was connected in
      series to a 5.5-mm inner diameter endotracheal tube with a filter (lung dose)
      interposed between them. Delivery efficiency was calculated as a percentage of
      the nominal dose captured on the filter. Albuterol content was analyzed by
      spectrophotometry (276 nm). RESULTS: No differences in lung dose/delivery
      efficiency were found at different V(T) values for the jet nebulizer (both
      positions) and the vibrating mesh nebulizer (ventilator). Lung dose/delivery
      efficiency was higher (P < .02) at a VT of 100 mL compared with the other volumes
      tested. The vibrating mesh nebulizer had higher lung dose/delivery efficiency
      compared with the jet nebulizer only when placed before the Y-piece. Moving the
      nebulizers from before the Y-piece to the ventilator increased lung dose/delivery
      efficiency for all conditions tested except the vibrating mesh nebulizer at a
      V(T) of 100 mL (P = .36). CONCLUSIONS: Optimization of inhaled drug delivery
      during pediatric mechanical ventilation should include careful selection of the
      type of delivery device and its placement in the ventilator circuit. Increasing
      V(T) during nebulization did not increase lung dose/delivery efficiency.

PMID- 25969514
TI  - Computerized Respiratory Sounds Are a Reliable Marker in Subjects With COPD.
AB  - BACKGROUND: Computerized respiratory sounds have shown potential in monitoring
      respiratory status in patients with COPD. However, the variability and
      reliability of this promising marker in COPD are unknown. Therefore, this study
      assessed the variability and reliability of respiratory sounds at distinct air
      flows and standardized anatomic locations in subjects with COPD. METHODS: A 2
      part study was conducted. Part 1 assessed the intra-subject reliability of
      respiratory sounds at spontaneous and target (0.4-0.6 and 0.7-1 L/s) air flows in
      13 out-patients (69.3 +/- 8.6 y old, FEV1 of 70.9 +/- 21.4% of predicted). Part 2
      characterized the inter-subject variability and intra-subject reliability of
      respiratory sounds at each standardized anatomic location, using the most
      reliable air flow, in a sample of 63 out-patients (67.3 +/- 10.4 y old, FEV1 of
      75.4 +/- 22.9% of predicted). Respiratory sounds were recorded simultaneously at
      7 anatomic locations (trachea and right and left anterior, lateral, and posterior
      chest). Air flow was recorded with a pneumotachograph. Normal respiratory sound
      intensity and mean number of crackles and wheezes were analyzed with validated
      algorithms. Inter-subject variability was assessed with the coefficient of
      variation, and intra-subject reliability was assessed with the intraclass
      correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Relative
      reliability was moderate to excellent for normal respiratory sound intensity and
      mean number of crackles (ICC of 0.66-0.89) and excellent for mean number of
      wheezes (ICC of 0.75-0.99) at the 3 air flows. Absolute reliability was greater
      at target air flows, especially at 0.4-0.6 L/s. Inter-subject variability was
      high for all respiratory sound parameters and across locations (coefficient of
      variation of 0.12-2.22). Respiratory sound parameters had acceptable relative and
      absolute intra-subject reliability at the different anatomic locations. The only
      exception was the mean number of crackles at the trachea, for which both relative
      and absolute reliability were poor. CONCLUSIONS: Respiratory sound parameters are
      more reliable at an air flow of 0.4-0.6 L/s and are reliable overall at all
      anatomic locations. This should be considered in future studies using
      computerized auscultation.

PMID- 25969515
TI  - Cognitive Behavioral Therapy for Management of Dyspnea: A Pilot Study.
AB  - BACKGROUND: In patients with COPD, psychological interventions usually target
      generalized anxiety and depression rather than the sensation of breathlessness.
      The objectives of this pilot study were to develop and implement a cognitive
      behavioral therapy (CBT) program specific to the perceptual experience of
      breathlessness, identify practical issues in the study protocol, and estimate
      beneficial effects of combining the CBT program with comprehensive pulmonary
      rehabilitation. METHODS: The CBT program for the sensation of breathlessness
      (Breathing: Recognize sensations, Explore thoughts and beliefs, Validate thoughts
      as useful or harmful, Evolve and change behavior [BREVE]) was developed as a
      sequential series of 8 modules enabling it to be embedded within an 8-week
      comprehensive pulmonary rehabilitation program. When appropriate, outcomes from
      the pilot group (comprehensive pulmonary rehabilitation program + BREVE) were
      compared with those from a retrospective control group (comprehensive pulmonary
      rehabilitation program only). Outcomes included feedback provided by pilot study
      subjects, sensation of breathlessness (volunteered and endorsed descriptors of
      breathlessness), 6-min walk distance (6MWD), and St George Respiratory
      Questionnaire (SGRQ) total score. Within-group analyses were undertaken for
      descriptors of breathlessness (the McNemar test), whereas between-group analyses
      (repeated-measures analysis of variance, effect-size comparison) were conducted
      for the 6MWD and SGRQ total score. RESULTS: Pilot (n = 11) and control (n = 58)
      groups were not significantly different at baseline. Feedback indicated that the
      program structure and content were positively received. No significant changes
      were evident for the sensation of breathlessness or the SGRQ score (< 4 points).
      The 6MWD improved significantly in both groups, with the pilot group
      demonstrating greater gains compared with the control group (mean change of 57 m
      and effect size of 0.73 vs mean change of 27 m and effect size of 0.23; between
      groups, P = .03, effect size of 0.69). CONCLUSION: The CBT program for the
      perceptual experience of breathlessness was feasible and well accepted by
      subjects, although the protocol raised a number of methodological limitations
      warranting modification. A larger randomized controlled trial is needed to
      determine the effectiveness and longer-term outcomes.

PMID- 25969516
TI  - Relationship Between Clinical Variables and Health-Related Quality of Life in
      Young Adult Subjects With Cystic Fibrosis.
AB  - BACKGROUND: Health-related quality of life (HRQOL) has received much attention in
      patients with cystic fibrosis (CF). The goal of this study was to evaluate the
      association between clinical, lung function, sleep quality, and polysomnographic
      variables with 2 HRQOL questionnaires, the shorter-version World Health
      Organization Quality of Life (WHOQOL-BREF) and Cystic Fibrosis Quality of Life
      (CFQOL) questionnaires, in adult subjects with CF. METHODS: In a cross-sectional
      study, 51 subjects underwent clinical evaluation and overnight polysomnography
      and answered WHOQOL-BREF, CFQOL, Pittsburgh Sleep Quality Index, and Epworth
      Sleepiness Scale questionnaires. In addition, pulmonary function tests, 6-min
      walk tests, and echocardiography were performed. RESULTS: For WHOQOL-BREF scores,
      the sleep quality index was associated with the physical domain; the percent-of
      predicted 6-min walk distance (6MWD) and sleepiness scale were associated with
      the psychological domain; the percent-of-predicted FEV1 and sleep quality index
      were associated with the social relationship domain; and the sleep quality index
      was associated with the environment domain. For CFQOL scores, age at diagnosis,
      clinical score, and sleep quality index were associated with the physical
      functioning domain; the percent-of-predicted 6MWD and pulmonary arterial systolic
      pressure were associated with the role domain; sex and sleep quality index were
      associated with the vitality domain; the apnea-hypopnea index was associated with
      the emotional functioning domain; sex and body mass index (BMI) were associated
      with the body image domain; the percent-of-predicted 6MWD and sleep quality index
      were associated with the health perception domain; age, sex, BMI, and arousal
      index were associated with the weight domain; age, sex, percent-of-predicted
      FEV1, percent-of-predicted 6MWD, and pulmonary arterial systolic pressure were
      associated with the respiratory symptom domain; and the clinical score was
      associated with the digestive symptom domain. CONCLUSIONS: The sleep quality
      index score, 6MWD, sleepiness scale score, and FEV1 were predictors of WHOQOL
      BREF scores. Age at diagnosis, clinical score, sleep quality score, 6MWD, sex,
      apnea-hypopnea index, BMI, current age, arousal index, FEV1, and pulmonary
      arterial systolic pressure were predictors of CFQOL scores.

PMID- 25969517
TI  - Foreign Body Inhalation in the Adult Population: Experience of 25,998
      Bronchoscopies and Systematic Review of the Literature.
AB  - BACKGROUND: Foreign body aspiration is an uncommon entity in adults. Herein, we
      describe our experience with flexible bronchoscopy in the removal of
      tracheobronchial foreign bodies in adults. We also conducted a systematic review
      of the literature on the topic of foreign body inhalation in adults managed with
      flexible bronchoscopy. METHODS: The bronchoscopy database (from 1979 to 2014) was
      reviewed for subjects > 12 y of age with a history of foreign body aspiration
      managed with flexible bronchoscopy. Demographic, clinical, and bronchoscopy data
      were collected and analyzed. PubMed was reviewed for studies describing the use
      of flexible bronchoscopy for foreign body extraction in adults. RESULTS: During
      the study period, a total of 25,998 flexible bronchoscopies were performed. Of
      these, 65 subjects (mean age of 32.8 y, 49 males) were identified who had
      undergone bronchoscopy for foreign body aspiration. Nonresolving pneumonia
      (30.6%), direct foreign body visualization (24.6%), and segmental collapse
      (18.4%) were the most common radiological abnormalities. Foreign bodies were
      identified in 49 cases during bronchoscopy and successfully removed in 45 (91.8%)
      subjects with no major complications. Metallic (41%) and organic (25.6%) foreign
      bodies were the most common. Shark-tooth (44.9%) and alligator (32.6%) were the
      most commonly used forceps in retrieving the foreign bodies. The systematic
      review yielded 18 studies (1,554 subjects with foreign body inhalation). In
      adults, the proportion of flexible bronchoscopy (6 studies, 354/159,074
      procedures) performed for the indication of foreign bodies among the total
      flexible bronchoscopies was 0.24% (95% CI 0.18-0.31). The overall success of
      flexible bronchoscopy (18 studies, 1,185 subjects) for foreign body extraction
      was 89.6% (95% CI 86.1-93.2). CONCLUSIONS: Foreign body aspiration is a rare
      indication for flexible bronchoscopy in adults. Flexible bronchoscopy has a high
      success rate in removal of inhaled foreign body and can be considered the
      preferred initial procedure for management of airway foreign bodies in adults.

PMID- 25969518
TI  - Toxoplasmosis in immunosuppressed patients.

PMID- 25969520
TI  - Variability of radiocaesium inventory in Fukushima soil cores from one site
      measured at different times.
AB  - The Fukushima Daiichi Nuclear Power Plant (FDNPP) accident has resulted in the
      deposition of radioactive contamination of soils mainly by (134)Cs and (137)Cs.
      The contaminated areas are of a great concern since external radiation may lead
      to significant long-term doses to humans and animals. External dose rate above
      ground will decrease with physical decay of the radionuclides and as they migrate
      deeper into the soil with time. In the present study, depth profiles of Cs
      radioisotopes have been studied at different times over a period of 1 y.
      Radiocaesium inventories for (134)Cs and (137)Cs down to a depth of 10 cm at the
      four measurement times varied from 2.09 to 4.14 MBq m(-2) with coefficient of
      variation (CV): 27.4 %, n = 4 and from 2.13 to 4.23 MBq m(-2) with CV: 27.3 %, n
      = 4, respectively. The activity ratio for (134)Cs/(137)Cs decreased from 0.62 to
      0.46 during 1 y of measurement i.e. July 2012 to June 2013. However, the ratio
      with decay correction (15 March 2011) was found to be constant ~1, indicating
      contamination from FDNPP origin. In order to understand the radiocaesium
      distribution in soil profile, physico-chemical characterisation of soil has been
      carried out. 

PMID- 25969521
TI  - Determination of subcellular compartment sizes for estimating dose variations in
      radiotherapy.
AB  - The variation in specific energy absorbed to different cell compartments caused
      by variations in size and chemical composition is poorly investigated in
      radiotherapy. The aim of this study was to develop an algorithm to derive cell
      and cell nuclei size distributions from 2D histology samples, and build 3D
      cellular geometries to provide Monte Carlo (MC)-based dose calculation engines
      with a morphologically relevant input geometry. Stained and unstained regions of
      the histology samples are segmented using a Gaussian mixture model, and
      individual cell nuclei are identified via thresholding. Delaunay triangulation is
      applied to determine the distribution of distances between the centroids of
      nearest neighbour cells. A pouring simulation is used to build a 3D virtual
      tissue sample, with cell radii randomised according to the cell size distribution
      determined from the histology samples. A slice with the same thickness as the
      histology sample is cut through the 3D data and characterised in the same way as
      the measured histology. The comparison between this virtual slice and the
      measured histology is used to adjust the initial cell size distribution into the
      pouring simulation. This iterative approach of a pouring simulation with
      adjustments guided by comparison is continued until an input cell size
      distribution is found that yields a distribution in the sliced geometry that
      agrees with the measured histology samples. The thus obtained morphologically
      realistic 3D cellular geometry can be used as input to MC-based dose calculation
      programs for studies of dose response due to variations in morphology and size of
      tumour/healthy tissue cells/nuclei, and extracellular material. 

PMID- 25969522
TI  - Optimisation of X-ray emission from a laser plasma source for the realisation of
      microbeam in sub-keV region.
AB  - In this work, the X-ray emission generated from a plasma produced by focusing Nd
      YAG laser beam on the Mylar and Yttrium targets will be characterised. The goal
      is to reach the best condition that optimises the X-ray conversion efficiency at
      500 eV (pre-edge of the Oxigen K-shell), strongly absorbed by carbon-based
      structures. The characteristics of the microbeam optical system, the
      software/hardware control and the preliminary measurements of the X-ray fluence
      will be presented. 

PMID- 25969523
TI  - High radon areas in the Walloon region of Belgium.
AB  - Indoor radon data from Southern Belgium are organised in 35 geological units
      (GUs), most of which are homogeneous with respect to the radon risk. The
      percentage of cases above the reference level (400 Bq m(-3); 300 Bq m(-3) in the
      future) is calculated for these GUs from the observations and from the log-normal
      distribution fitted to the data. Affected areas are defined as areas with more
      than 1 % of houses above the reference level. In the north of the region, the old
      Palaeozoic basement is generally covered by Silesian, Cretaceous and Tertiary
      rocks, which are unaffected. The affected areas here are hot spots associated
      with specific Palaeozoic outcrops. In the south, there is generally no cover
      above Palaeozoic formations, which are often radon affected. The affected areas
      of Ardenne and Condroz dominate this part, but unaffected areas occur like
      Famenne and Gaume. About 48 % of the Walloon region is expected to be radon
      affected. 

PMID- 25969524
TI  - Deterministic effect of lens at leukergy of patients who received low doses of
      ionising radiation.
AB  - To explore the possibility to use the lens extract as an in vitro stimulator to
      conduct a test of stimulated leukergy in liquidators of the accident consequences
      (LAC) on Chernobyl Nuclear Power Plant (CNPP) with a cataract in the long-term
      period. The study sample included 72 men-LAC on CNPP, at the age from 42 to 65 y,
      who have a cataract. The comparison group consisted of 60 men, with a cataract,
      of the same age, and who were not exposed to radiation. The control group was
      composed of 60 men, at the age of 42-58 y without lens pathology. Phenomenon of
      the stimulated leukergy was revealed in persons who had been exposed to radiation
      in the dose of 18.2 +/- 0.58 cGy and was observed in 5.7-8.05 % (P < 0.001),
      suggesting a continued high auto-aggression to the lens antigens, and the
      strength of cell-mediated immunity.

PMID- 25969525
TI  - Fifteen symposia on microdosimetry: implications for modern particle-beam cancer
      radiotherapy.
AB  - The objective of microdosimetry was, and still is, to identify physical
      descriptions of the initial physical processes of ionising radiation interacting
      with biological matter which correlate with observed radiobiological effects with
      a view to improve the understanding of radiobiological mechanisms and effects.
      The introduction of therapy with particles starting with fast neutrons followed
      by negative pions, protons and light ions necessitated the application of
      biological weighting factors for absorbed dose in order to account for
      differences of the relative biological effectiveness (RBE). Dedicated
      radiobiological experiments in therapy beams with mammalian cells and with
      laboratory animals provided sets of RBE values which are used to evaluate
      empirical 'clinical RBE values'. The combination of such experiments with
      microdosimetric measurements in identical conditions offered the possibility to
      establish semi-empirical relationships between microdosimetric parameters and
      results of RBE studies. 

PMID- 25969526
TI  - EUTEMPE-RX, an EC supported FP7 project for the training and education of medical
      physics experts in radiology.
AB  - The core activity of the medical physics expert (MPE) is to ensure optimal use of
      ionising radiation in healthcare. It is essential that these healthcare
      professionals are trained to the highest level, defined as European
      Qualifications Framework for Lifelong Learning (EQF) level 8 by the European
      Commission's Radiation Protection Report 174 'Guidelines on the MPE'. The main
      objective of the EUTEMPE-RX project is to provide a model training scheme that
      allows the medical physicist in diagnostic and interventional radiology (D&IR) to
      reach this high level. A European network of partners was brought together in
      this FP7 EC project to ensure sufficient expertise in all aspects of the subject
      and to create a harmonised course programme. Targeted participants are medical
      physicists in D&IR in hospitals, engineers and scientists in medical device
      industries and officers working in regulatory authorities. Twelve course modules
      will be developed at EQF level 8, with radiation safety and diagnostic
      effectiveness being prevalent subjects. The modules will combine online with face
      to-face teaching using a blended learning approach. 

PMID- 25969528
TI  - Cross-section scaling for track structure simulations of low-energy ions in
      liquid water.
AB  - Radiation damage by low-energy ions significantly contributes to the high
      biological efficiency of ion beams in distal Bragg peak regions as well as to the
      energy-dependent efficiency of neutron irradiation. To enable assessing
      biological effects of ions at energies <1 MeV u(-1) with track-structure based
      models, a Barkas-like scaling procedure is developed that provides ion cross
      sections in liquid water based on those for hydrogen ions. The resulting stopping
      power and range for carbon ions agree with the ICRU 73 database and other low
      energy stopping power data. The method represents the basis for extending PARTRAC
      simulations of light ion track structures and biological effects down to the keV
      u(-1) range. 

PMID- 25969527
TI  - Glioblastoma stem cells: radiobiological response to ionising radiations of
      different qualities.
AB  - Glioblastoma multiforme (GBM) is the most common and malignant primary brain
      tumour, with very poor prognosis. The high recurrence rate and failure of
      conventional treatments are expected to be related to the presence of radio
      resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self
      renew and differentiate into the heterogeneous lineages of cancer cells. Recent
      evidence showed a higher effectiveness of C-ions and protons in inactivating
      CSCs, suggesting a potential advantage of Hadrontherapy compared with
      conventional radiotherapy for GBM treatment. To investigate the mechanisms
      involved in the molecular and cellular responses of CSCs to ionising radiations,
      two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from
      patients with different clinical outcomes and having different metabolic profiles
      (as shown by NMR spectroscopy), were irradiated with (137)Cs photons and with
      protons or C-ions of 62 MeV u(-1) in the dose range of 5-40 Gy. The biological
      effects investigated were: cell death, cell cycle progression, and DNA damage
      induction and repair. Preliminary results show a different response to ionising
      radiation between the two GSC lines for the different end points investigated.
      Further experiments are in progress to consolidate the data and to get more
      insights on the influence of radiation quality. 

PMID- 25969529
TI  - MSL-RAD radiation environment measurements.
AB  - In this study, results are presented from the on-board radiation assessment
      detector (RAD) of Mars Science Laboratory (MSL). RAD is designed to measure the
      energetic particle radiation environment, which consists of galactic cosmic rays
      (GCRs) and solar energetic particles (SEPs) as well as secondary particles
      created by nuclear interactions of primary particles in the shielding (during
      cruise) or Martian soil and atmosphere (surface measurements). During the cruise,
      RAD collected data on space radiation from inside the craft, thus allowing for a
      reasonable estimation of what a human crew travelling to/from Mars might be
      exposed to. On the surface of Mars, RAD is shielded by the atmosphere (from
      above) and the planet itself (from below). RAD measures the first detailed
      radiation data from the surface of another planet, and they are highly relevant
      for planning future crewed missions. The results for radiation dose and dose
      equivalent (a quantity most directly related to human health risk) are presented
      during the cruise phase, as well as on the Martian surface. Dose and dose
      equivalent are dominated by the continuous GCR radiation, but several SEP events
      were also detected and are discussed here. 

PMID- 25969530
TI  - Variants in the Mannose-binding Lectin Gene MBL2 do not Associate With Sepsis
      Susceptibility or Survival in a Large European Cohort.
AB  - BACKGROUND: Sepsis is an increasingly common condition, which continues to be
      associated with unacceptably high mortality. A large number of association
      studies have investigated susceptibility to, or mortality from, sepsis for
      variants in the functionally important immune-related gene MBL2. These studies
      have largely been underpowered and contradictory. METHODS: We genotyped and
      analyzed 4 important MBL2 single nucleotide polymorphisms (SNPs; rs5030737,
      rs1800450, rs1800451, and rs7096206) in 1839 European community-acquired
      pneumonia (CAP) and peritonitis sepsis cases, and 477 controls from the United
      Kingdom. We analyzed the following predefined subgroups and outcomes: 28-day and
      6 month mortality from sepsis due to CAP or peritonitis combined, 28-day
      mortality from CAP sepsis, peritonitis sepsis, pneumococcal sepsis or sepsis in
      younger patients, and susceptibility to CAP sepsis or pneumococcal sepsis in the
      United Kingdom. RESULTS: There were no significant associations (all P-values
      were greater than .05 after correction for multiple testing) between MBL2
      genotypes and any of our predefined analyses. CONCLUSIONS: In this large, well
      defined cohort of immune competent adult patients, no associations between MBL2
      genotype and sepsis susceptibility or outcome were identified.

PMID- 25969531
TI  - Intermittent Directly Observed Therapy for Abdominal Tuberculosis: A Multicenter
      Randomized Controlled Trial Comparing 6 Months Versus 9 Months of Therapy.
AB  - BACKGROUND: The duration of treatment of gastrointestinal tuberculosis continues
      to be a matter of debate. The World Health Organization advocates intermittent
      directly observed short-course therapy (DOTs), but there is a lack of data of its
      efficacy in abdominal tuberculosis. We therefore conducted a multicenter
      randomized controlled trial to compare 6 months and 9 months of antituberculosis
      therapy using DOTs. METHODS: One hundred ninety-seven patients with abdominal
      tuberculosis (gastrointestinal, 154; peritoneal, 40; mixed, 3) were randomized to
      receive 6 months (n = 104) or 9 months (n = 93) of antituberculosis therapy using
      intermittent directly observed therapy. Patients were followed up 1 year after
      completion of treatment to assess recurrence. Patients were evaluated for primary
      endpoint (complete clinical response, partial response, and no response) and
      secondary endpoint (recurrence of the disease at the end of 1 year of follow-up).
      RESULTS: Baseline characteristics were similar between the 2 randomized groups.
      There was no difference between the 6-month group and 9-month group in the
      complete clinical response rate on per-protocol analysis (91.5% vs 90.8%; P =
      .88) or intent-to-treat analysis (75% vs 75.8%; P = .89). Only 1 patient in the 9
      month group and no patients in the 6-month group had recurrence of disease. Side
      effects occurred in 21 (21.3%) and 16 (18.2%) patients in the 6-month and 9-month
      groups, respectively. CONCLUSIONS: There was no difference in efficacy of
      antituberculosis therapy delivered for either 6 months or 9 months in either
      gastrointestinal or peritoneal tuberculosis, confirming the efficacy of
      intermittent directly observed therapy. CLINICAL TRIALS REGISTRATION:
      NCT01124929.

PMID- 25969532
TI  - Editorial Commentary: Shall We Disregard Mannose-Binding Lectin Modification in
      the Future Because We Cannot Prevent Sepsis With This Molecule?

PMID- 25969533
TI  - Functionally distinct amygdala subregions identified using DTI and high
      resolution fMRI.
AB  - Although the amygdala is often directly linked with fear and emotion, amygdala
      neurons are activated by a wide variety of emotional and non-emotional stimuli.
      Different subregions within the amygdala may be engaged preferentially by
      different aspects of emotional and non-emotional tasks. To test this hypothesis,
      we measured and compared the effects of novelty and fear on amygdala activity. We
      used high-resolution blood oxygenation level-dependent (BOLD) imaging and
      streamline tractography to subdivide the amygdala into three distinct functional
      subunits. We identified a laterobasal subregion connected with the visual cortex
      that responds generally to visual stimuli, a non-projecting region that responds
      to salient visual stimuli, and a centromedial subregion connected with the
      diencephalon that responds only when a visual stimulus predicts an aversive
      outcome. We provide anatomical and functional support for a model of amygdala
      function where information enters through the laterobasal subregion, is processed
      by intrinsic circuits in the interspersed tissue, and is then passed to the
      centromedial subregion, where activation leads to behavioral output. 

PMID- 25969534
TI  - Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly
      Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.
AB  - Little is known about the regulation of the oncomiR miR-21 in liver.
      Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G
      protein-coupled receptor and as a precursor for steroids that activate nuclear
      receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR
      21) transcription and mature miR-21 expression in HepG2 cells in a biphasic
      manner with an initial peak at 1 h followed by a second, sustained response from
      3-12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells.
      siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated
      increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30),
      estrogen receptor alpha-36 (ERalpha36), epidermal growth factor receptor
      dependent, pertussis toxin-sensitive pathway requiring activation of c-Src,
      ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA
      stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant
      increased pri-miR-21 in a GPER- and ERalpha36-dependent manner. DHEA, like G-1,
      increased GPER and ERalpha36 mRNA and protein levels. DHEA increased ERK1/2 and c
      Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c
      Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c
      Jun recruitment to the miR-21 promoter. These results suggest that physiological
      concentrations of DHEA activate a GPER intracellular signaling cascade that
      increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen
      receptor miR-21 promoter interaction. 

PMID- 25969535
TI  - Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in
      Gap Junction Channels Composed of Connexin32.
AB  - Tryptophan was substituted for residues in all four transmembrane domains of
      connexin32. Function was assayed using dual cell two-electrode voltage clamp
      after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated
      in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15
      substitutions were made, six abolished coupling and five others significantly
      reduced function. Only TM2 and TM3 included a distinct helical face that lacked
      sensitivity to tryptophan substitution. Results were visualized on a comparative
      model of Cx32 hemichannel. In this model, a region midway through the membrane
      appears highly sensitive to tryptophan substitution and includes residues Arg-32,
      Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1
      and TM2 were highly sensitive to tryptophan substitution, whereas the lipid
      facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative
      intracellular water pocket (the IC pocket) were also highly sensitive to
      tryptophan substitution. Although future studies will be required to separate
      trafficking-defective mutants from those that alter channel function, a subset of
      interactions important for voltage gating was identified. Interactions important
      for voltage gating occurred mainly in the mid-region of the channel and focused
      on TM1. To determine whether results could be extrapolated to other connexins,
      TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of
      Cx32. 

PMID- 25969536
TI  - Ubiquitin-specific Protease 11 (USP11) Deubiquitinates Hybrid Small Ubiquitin
      like Modifier (SUMO)-Ubiquitin Chains to Counteract RING Finger Protein 4 (RNF4).
AB  - Ring finger protein 4 (RNF4) is a SUMO-targeted ubiquitin E3 ligase with a
      pivotal function in the DNA damage response (DDR). SUMO interaction motifs (SIMs)
      in the N-terminal part of RNF4 tightly bind to SUMO polymers, and RNF4 can
      ubiquitinate these polymers in vitro. Using a proteomic approach, we identified
      the deubiquitinating enzyme ubiquitin-specific protease 11 (USP11), a known DDR
      component, as a functional interactor of RNF4. USP11 can deubiquitinate hybrid
      SUMO-ubiquitin chains to counteract RNF4. SUMO-enriched nuclear bodies are
      stabilized by USP11, which functions downstream of RNF4 as a counterbalancing
      factor. In response to DNA damage induced by methyl methanesulfonate, USP11 could
      counteract RNF4 to inhibit the dissolution of nuclear bodies. Thus, we provide
      novel insight into cross-talk between ubiquitin and SUMO and uncover USP11 and
      RNF4 as a balanced SUMO-targeted ubiquitin ligase/protease pair with a role in
      the DDR. 

PMID- 25969537
TI  - Members of the Plant CRK Superfamily Are Capable of Trans- and
      Autophosphorylation of Tyrosine Residues.
AB  - Protein phosphorylation on Tyr residues is a key post-translational modification
      in mammals. In plants, recent studies have identified Tyr-specific protein
      phosphatase and Tyr-phosphorylated proteins in Arabidopsis by phosphoproteomic
      screenings, implying that plants have a Tyr phosphorylation signal pathway.
      However, little is known about the protein kinases (PKs) involved in Tyr
      phosphorylation in plants. Here, we demonstrate that Arabidopsis calcium
      dependent protein kinase (CDPK/CPK)-related PKs (CRKs) have high Tyr
      autophosphorylation activity and that they can phosphorylate Tyr residue(s) on
      substrate proteins in Arabidopsis. To identify PKs for Tyr phosphorylation, we
      examined the autophosphorylation activity of 759 PKs using an Arabidopsis protein
      array based on a wheat cell-free system. In total, we identified 38 PKs with Tyr
      autophosphorylation activity. The CRK family was a major protein family
      identified. A cell-free substrate screening revealed that these CRKs
      phosphorylate beta-tubulin (TBB) 2, TBB7, and certain transcription factors (TFs)
      such as ethylene response factor 13 (ERF13). All five CRKs tested showed Tyr
      auto/trans-phosphorylation activity and especially two CRKs, CRK2 and CRK3,
      showed a high ERF13 Tyr-phosphorylation activity. A cell-based transient
      expression assay revealed that Tyr(16/)Tyr(207) sites in ERF13 were
      phosphorylated by CRK3 and that Tyr phosphorylation of endogenous TBBs occurs in
      CRK2 overexpressing cells. Furthermore, crk2 and crk3 mutants showed a decrease
      in the Tyr phosphorylation level of TBBs. These results suggest that CRKs have
      Tyr kinase activity, and these might be one of the major PKs responsible for
      protein Tyr phosphorylation in Arabidopsis plants. 

PMID- 25969538
TI  - Calreticulin and Arginylated Calreticulin Have Different Susceptibilities to
      Proteasomal Degradation.
AB  - Post-translational arginylation has been suggested to target proteins for
      proteasomal degradation. The degradation mechanism for arginylated calreticulin
      (R-CRT) localized in the cytoplasm is unknown. To evaluate the effect of
      arginylation on CRT stability, we examined the metabolic fates and degradation
      mechanisms of cytoplasmic CRT and R-CRT in NIH 3T3 and CHO cells. Both CRT
      isoforms were found to be proteasomal substrates, but the half-life of R-CRT (2
      h) was longer than that of cytoplasmic CRT (0.7 h). Arginylation was not required
      for proteasomal degradation of CRT, although R-CRT displays ubiquitin
      modification. A CRT mutant incapable of dimerization showed reduced metabolic
      stability of R-CRT, indicating that R-CRT dimerization may protect it from
      proteasomal degradation. Our findings, taken together, demonstrate a novel
      function of arginylation: increasing the half-life of CRT in cytoplasm. 

PMID- 25969540
TI  - Reassessing noninducibility as ablation endpoint of post-infarction ventricular
      tachycardia: the impact of left ventricular function.
AB  - BACKGROUND: Noninducibility is frequently used as procedural end point of
      ventricular tachycardia (VT) ablation after myocardial infarction. We
      investigated the influence of left ventricular (LV) function on the predictive
      value of noninducibility for VT recurrence and cardiac mortality. METHODS AND
      RESULTS: Ninety-one patients (82 men, 67+/-10 years) with post-myocardial
      infarction VT underwent ablation between 2009 and 2012. Fifty-nine (65%) had an
      LV ejection fraction (EF) >30% (mean 41+/-7) and 32 (35%) an LVEF<=30% (mean 20+/
      5). Thirty patients (51%) with EF>30% and 13 (41%) with EF<=30% were noninducible
      after ablation (P=0.386). During a median follow-up of 23 (Q1-Q3 16-36) months,
      35 patients (38%) experienced VT recurrences and 17 (18%) cardiac death. At 1
      year follow-up, survival free from VT recurrence and cardiac death for patients
      with LVEF>30% was 80% (95% confidence interval [CI], 70-90) compared with 42%
      (95% CI, 33-51) for those with LVEF<=30% (P=0.001). Noninducible patients with
      LVEF>30% had a recurrence-free survival from cardiac death of 90% (95% CI, 71
      100) compared with 65% (95% CI, 47-83) for inducible patients (P=0.015). In the
      subgroup of patients with LVEF<=30%, the survival free from VT recurrence and
      cardiac death was 31% (95% CI, 0%-60%) for noninducible compared with 39% (95%
      CI, 27-52) for those who remained inducible (P=0.842). CONCLUSIONS: Noninducible
      patients with moderately depressed LV function have a favorable outcome compared
      with patients who remained inducible after ablation. On the contrary, patients
      with severely depressed LV function have a poor prognosis independent of the
      acute procedural outcome.

PMID- 25969541
TI  - Interpretation of laboratory detection trends for Chlamydia trachomatis and
      Neisseria gonorrhoeae: Manitoba, Canada, 2000-2012.
AB  - OBJECTIVES: Increases in case numbers for Chlamydia trachomatis (CT) and
      Neisseria gonorrhoeae (NG) have been noted on a global level. This study analysed
      13 years of testing data to better understand case detection trends over time.
      METHODS: Data consisted of all nucleic acid probe and nucleic acid amplification
      diagnostic testing for CT and NG for the population of Manitoba, Canada (1.2
      million); January 2000 to December 2012. Logistic regression models were used to
      analyse ORs associated with positive CT and NG tests by year. Included in the
      model as predictor variables were test type, specimen type, patient age and
      residence location. RESULTS: For both male and female CT results, unadjusted OR
      by year mimicked absolute case counts, reflecting a general increase over time in
      case counts. Adjustment for laboratory-related variables altered this
      relationship such that a general decline in the odds of identifying a CT case
      over time was evident. For both male and female NG results, adjustment for
      laboratory and demographic variables altered the OR associated with each year,
      but to a lesser extent than for CT. CONCLUSIONS: Temporal trends associated with
      CT case numbers should be interpreted after controlling, at a minimum, for the
      influence of laboratory-related variables. Interpretation of NG trends is
      feasible using only the number of reported NG cases.

PMID- 25969539
TI  - Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic beta Cells:
      ROLES IN REGULATING CYTOSOLIC ZINC HOMEOSTASIS AND INSULIN SECRETION.
AB  - Zinc plays an essential role in the regulation of pancreatic beta cell function,
      affecting important processes including insulin biosynthesis, glucose-stimulated
      insulin secretion, and cell viability. Mutations in the zinc efflux transport
      protein ZnT8 have been linked with both type 1 and type 2 diabetes, further
      supporting an important role for zinc in glucose homeostasis. However, very
      little is known about how cytosolic zinc is controlled by zinc influx
      transporters (ZIPs). In this study, we examined the beta cell and islet ZIP
      transcriptome and show consistent high expression of ZIP6 (Slc39a6) and ZIP7
      (Slc39a7) genes across human and mouse islets and MIN6 beta cells. Modulation of
      ZIP6 and ZIP7 expression significantly altered cytosolic zinc influx in
      pancreatic beta cells, indicating an important role for ZIP6 and ZIP7 in
      regulating cellular zinc homeostasis. Functionally, this dysregulated cytosolic
      zinc homeostasis led to impaired insulin secretion. In parallel studies, we
      identified both ZIP6 and ZIP7 as potential interacting proteins with GLP-1R by a
      membrane yeast two-hybrid assay. Knock-down of ZIP6 but not ZIP7 in MIN6 beta
      cells impaired the protective effects of GLP-1 on fatty acid-induced cell
      apoptosis, possibly via reduced activation of the p-ERK pathway. Therefore, our
      data suggest that ZIP6 and ZIP7 function as two important zinc influx
      transporters to regulate cytosolic zinc concentrations and insulin secretion in
      beta cells. In particular, ZIP6 is also capable of directly interacting with GLP
      1R to facilitate the protective effect of GLP-1 on beta cell survival. 

PMID- 25969542
TI  - Phosphorylation of GATA-6 is required for vascular smooth muscle cell
      differentiation after mTORC1 inhibition.
AB  - Vascular smooth muscle cells (VSMCs) undergo transcriptionally regulated
      reversible differentiation in growing and injured blood vessels. This
      dedifferentiation also contributes to VSMC hyperplasia after vascular injury,
      including that caused by angioplasty and stenting. Stents provide mechanical
      support and can contain and release rapamycin, an inhibitor of the mechanistic
      target of rapamycin complex 1 (mTORC1). Rapamycin suppresses VSMC hyperplasia and
      promotes VSMC differentiation. We report that rapamycin-induced differentiation
      of VSMCs required the transcription factor GATA-6. Inhibition of mTORC1
      stabilized GATA-6 and promoted the nuclear accumulation of GATA-6, its binding to
      DNA, its transactivation of promoters encoding contractile proteins, and its
      inhibition of proliferation. These effects were mediated by phosphorylation of
      GATA-6 at Ser(290), potentially by Akt2, a kinase that is activated in VSMCs when
      mTORC1 is inhibited. Rapamycin induced phosphorylation of GATA-6 in wild-type
      mice, but not in Akt2(-/-) mice. Intimal hyperplasia after arterial injury was
      greater in Akt2(-/-) mice than in wild-type mice, and the exacerbated response in
      Akt2(-/-) mice was rescued to a greater extent by local overexpression of the
      wild-type or phosphomimetic (S290D) mutant GATA-6 than by that of the
      phosphorylation-deficient (S290A) mutant. Our data indicated that GATA-6 and Akt2
      are involved in the mTORC1-mediated regulation of VSMC proliferation and
      differentiation. Identifying the downstream transcriptional targets of mTORC1 may
      provide cell type-specific drug targets to combat cardiovascular diseases
      associated with excessive proliferation of VSMCs. 

PMID- 25969544
TI  - EGFR-activated Src family kinases maintain GAB1-SHP2 complexes distal from EGFR.
AB  - Complexes of signaling proteins that are nucleated upon activation of receptor
      tyrosine kinases are dynamic macromolecular assemblies held together by
      interactions, such as the recognition of phosphotyrosines by Src homology 2 (SH2)
      domains. We predicted that reversible binding and phosphatase activity enable
      dynamic regulation of these protein complexes, which could affect signal
      transduction. We explored how dynamics in the interactions among the epidermal
      growth factor (EGF) receptor (EGFR), GRB2-associated binder protein 1 (GAB1), and
      SH2 domain-containing phosphatase 2 (SHP2) affected EGFR signaling output,
      specifically SHP2 binding to tyrosine-phosphorylated GAB1, which relieves the
      autoinhibition of SHP2. Among the effects of activated SHP2 is increased
      extracellular signal-regulated kinase (ERK) activity. We found that in H1666 lung
      adenocarcinoma cells, EGFR-activated Src family kinases (SFKs) counteracted
      repeated GAB1 dephosphorylation events and maintained the association of SHP2
      with phosphorylated GAB1 at a cytosolic site distal from EGFR. A computational
      model predicted that an experimentally verified delay in SFK inactivation after
      EGFR inactivation, combined with an amplification of GAB1 phosphorylation in
      cells with proteins in a specific range of concentrations, enabled GAB1
      phosphorylation and GAB1-SHP2 complexes to persist longer than EGFR
      phosphorylation persisted in response to EGF. This SFK-dependent mechanism was
      specific to EGFR and did not occur in response to activation of the receptor
      tyrosine kinase c-MET. Thus, our results quantitatively describe a regulatory
      mechanism used by some receptor tyrosine kinases to remotely control the duration
      of a signal by regulating the persistence of a signaling protein complex. 

PMID- 25969543
TI  - Activation of MyD88-dependent TLR1/2 signaling by misfolded alpha-synuclein, a
      protein linked to neurodegenerative disorders.
AB  - Synucleinopathies, such as Parkinson's disease and diffuse Lewy body disease, are
      progressive neurodegenerative disorders characterized by selective neuronal
      death, abnormal accumulation of misfolded alpha-synuclein, and sustained
      microglial activation. In addition to inducing neuronal toxicity, higher-ordered
      oligomeric alpha-synuclein causes proinflammatory responses in the brain
      parenchyma by triggering microglial activation, which may exacerbate pathogenic
      processes by establishing a chronic neuroinflammatory milieu. We found that
      higher-ordered oligomeric alpha-synuclein induced a proinflammatory microglial
      phenotype by directly engaging the heterodimer TLR1/2 (Toll-like receptor 1 and
      2) at the cell membrane, leading to the nuclear translocation of NF-kappaB
      (nuclear factor kappaB) and the increased production of the proinflammatory
      cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-1beta (interleukin
      1beta) in a MyD88-dependent manner. Blocking signaling through the TLR1/2
      heterodimer with the small-molecule inhibitor CU-CPT22 reduced the nuclear
      translocation of NF-kappaB and secretion of TNF-alpha from cultured primary mouse
      microglia. Candesartan cilexetil, a drug approved for treating hypertension and
      that inhibits the expression of TLR2, reversed the activated proinflammatory
      phenotype of primary microglia exposed to oligomeric alpha-synuclein, supporting
      the possibility of repurposing this drug for synucleinopathies. 

PMID- 25969545
TI  - Wire-Interwoven Nitinol Stent Outcome in the Superficial Femoral and Proximal
      Popliteal Arteries: Twelve-Month Results of the SUPERB Trial.
AB  - BACKGROUND: Stent-based therapy in the superficial femoral and popliteal arteries
      in patients with peripheral artery disease is compromised by restenosis and risk
      of stent fracture or distortion. A novel self-expanding nitinol stent was
      developed that incorporates an interwoven-wire design (Supera stent, IDEV
      Technologies, Inc, Webster, TX) to confer greater radial strength, flexibility,
      and fracture resistance. METHODS AND RESULTS: This prospective, multicenter,
      investigational device exemption, single-arm trial enrolled 264 patients with
      symptomatic peripheral artery disease undergoing percutaneous treatment of de
      novo or restenotic lesions of the superficial femoral or proximal popliteal
      (femoropopliteal) artery. Freedom from death, target lesion revascularization, or
      any amputation of the index limb at 30 days (+ 7 days) postprocedure was achieved
      in 99.2% (258/260) of patients (P < 0.001). Primary patency at 12 months (360 +/-
      30 days) was achieved in 78.9% (180/228) of the population (P < 0.001). Primary
      patency by Kaplan-Meier analysis at 12 months (360 days) was 86.3%. No stent
      fracture was observed by independent core laboratory analysis in the 243 stents
      (228 patients) evaluated at 12 months. Clinical assessment at 12 months
      demonstrated improvement by at least 1 Rutherford-Becker category in 88.7% of
      patients. CONCLUSIONS: The SUPERB Trial, an investigational device exemption
      study using an interwoven nitinol wire stent in the femoropopliteal artery,
      achieved the efficacy and safety performance goals predesignated by the Food and
      Drug Administration. On the basis of the high primary patency rate, absence of
      stent fracture, and significant improvements in functional and quality-of-life
      measures, the Supera stent provides safe and effective treatment of
      femoropopliteal lesions in symptomatic patients with peripheral artery disease.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00933270.

PMID- 25969546
TI  - Association of smoking status with health-related outcomes after percutaneous
      coronary intervention.
AB  - BACKGROUND: Patients who smoke at the time of percutaneous coronary intervention
      (PCI) would ideally have a strong incentive to quit, but most do not. We sought
      to compare the health status outcomes of those who did and did not quit smoking
      after PCI with those who were not smoking before PCI. METHODS AND RESULTS: A
      cohort of 2765 PCI patients from 10 US centers were categorized into never, past
      (smoked in the past but had quit before PCI), quitters (smoked at time of PCI but
      then quit), and persistent smokers. Health status was measured with the disease
      specific Seattle Angina Questionnaire and the EuroQol 5 dimensions, adjusted for
      baseline characteristics. In unadjusted analyses, persistent smokers had worse
      disease-specific and overall health status when compared with other groups. In
      fully adjusted analyses, persistent smokers showed significantly worse health
      related quality of life when compared with never smokers. Importantly, of those
      who smoked at the time of PCI, quitters had significantly better adjusted Seattle
      Angina Questionnaire angina frequency scores (mean difference, 2.73; 95%
      confidence interval, 0.13-5.33) and trends toward higher disease specific
      (Seattle Angina Questionnaire quality of life mean difference, 1.97; 95%
      confidence interval, -1.24 to 5.18), and overall (EuroQol 5 dimension visual
      analog scale scores mean difference, 2.45; 95% confidence interval, -0.58 to
      5.49) quality of life when compared with persistent smokers at 12 months.
      CONCLUSIONS: Smokers at the time of PCI have worse health status at 1 year than
      those who never smoked, whereas smokers who quit after PCI have less angina at 1
      year than those who continue smoking.

PMID- 25969547
TI  - Angiographic and optical coherence tomography insights into bioresorbable
      scaffold thrombosis: single-center experience.
AB  - BACKGROUND: As bioresorbable vascular scaffolds (BVSs) are being increasingly
      used in complex real-world lesions and populations, BVS thrombosis cases have
      been reported. We present angiographic and optical coherence tomography (OCT)
      findings in a series of patients treated in our center for definite bioresorbable
      scaffold thrombosis. METHODS AND RESULTS: Up to June 2014, 14 patients presented
      with definite BVS thrombosis in our center. OCT was performed in 9 patients at
      the operator's discretion. Angiographic and OCT findings were compared with a
      control group comprising 15 patients with definite metallic stent thrombosis. In
      the BVS group, time interval from index procedure to scaffold thrombosis ranged
      from 0 to 675 days. Incomplete lesion coverage by angiography was identified in 4
      of 14 cases, malapposition by OCT in 5 of 9 cases, strut discontinuity in 2 of 9
      cases, and underexpansion in 2 of 9 cases. Five patients had discontinued dual
      antiplatelet therapy, and in 3 of them discontinued dual antiplatelet therapy
      discontinuation had occurred the week preceding the event. There were no
      significant differences in angiographic or OCT findings between BVS and metallic
      stent thrombosis. CONCLUSIONS: Suboptimal implantation with incomplete lesion
      coverage, underexpansion, and malapposition comprises the main pathomechanism for
      both early and late BVS thrombosis, similar to metallic stent thrombosis. Dual
      antiplatelet therapy discontinuation seems to also be a secondary contributor in
      several late events. Our observations suggest that several potential triggers for
      BVS thrombosis could be avoided.

PMID- 25969548
TI  - Smoke signals: urgent need for more successful interventions.

PMID- 25969549
TI  - Which is the best graft for the right coronary artery?

PMID- 25969550
TI  - Editor's Choice-Extracorporeal life support for out-of-hospital cardiac arrest:
      Part of a treatment bundle.
AB  - In recent years, an increasing number of papers have been published on the use of
      extracorporeal cardiopulmonary resuscitation (ECPR) in adult patients, but,
      although promising results have been reported in patients with in-hospital
      refractory cardiac arrest supported by extracorporeal life support (ECLS), data
      on patients with out-of-hospital (OHCA) cardiac arrest are scarce and
      conflicting. The present study aims at summarizing the available evidence on the
      use of ECPR in adult patients with OHCA, clinically focusing on the factors most
      often associated with outcome in these patients. Even in the absence of
      randomized trials, there is growing evidence from ECLS centers documenting sound
      clinical benefits of ECPR in selected OHCA. According to the available evidence,
      three factors seem to contribute strongly to the favorable outcome of ECLS
      supported OHCA patients: (a) selection of patients (mainly definition of age
      range and a witnessed cardiac arrest); (b) the availability of an ECLS team, well
      skilled and experienced (to reduce time of implantation and incidence of
      complications); (c) a multifaceted approach to the OHCA patient (the so-called
      ECLS-bundle) to treat the reversible cause of CA (i.e. percutaneous coronary
      intervention), ensure neuroprotection (hypothermia), and maintain organ perfusion
      (till recovery). Taking into account the promising results of ECPR in selected
      OHCA patients, there is a clinical need for shared protocols to reduce
      differences related to the center experience and mostly to increase availability
      of ECLS as part of a multifaceted approach for these patients.

PMID- 25969551
TI  - Cysteine-rich receptor-like kinase CRK5 as a regulator of growth, development,
      and ultraviolet radiation responses in Arabidopsis thaliana.
AB  - In plants, receptor-like protein kinases play essential roles in signal
      transduction by recognizing extracellular stimuli and activating the downstream
      signalling pathways. Cysteine-rich receptor-like kinases (CRKs) constitute a
      large subfamily of receptor-like protein kinases, with 44 members in Arabidopsis
      thaliana. They are distinguished by the novel C-X8-C-X2-C motif (DUF26) in the
      extracellular domains. One of them, CRK5, is an important component of the
      biochemical machinery involved in the regulation of essential physiological
      processes. Functional characterization of crk5 mutant plants showed their clear
      phenotype, manifested by impaired stomatal conductance and accelerated
      senescence. This phenotype correlated with accumulation of reactive oxygen
      species, higher foliar levels of ethylene and salicylic acid, and increased
      transcript abundance for genes associated with signalling pathways corresponding
      to these hormones. Moreover, the crk5 plants displayed enhanced cell death and
      oxidative damage in response to ultraviolet radiation. Complementation of CRK5
      mutation managed to recover the wild-type phenotype, indicating an essential role
      of this gene in the regulation of growth, development, and acclimatory responses.

PMID- 25969552
TI  - Prolonged expression of the BX1 signature enzyme is associated with a
      recombination hotspot in the benzoxazinoid gene cluster in Zea mays.
AB  - Benzoxazinoids represent preformed protective and allelopathic compounds. The
      main benzoxazinoid in maize (Zea mays L.) is 2,4-dihydroxy-7-methoxy-1,4
      benzoxazin-3-one (DIMBOA). DIMBOA confers resistance to herbivores and microbes.
      Protective concentrations are found predominantly in young plantlets. We made use
      of the genetic diversity present in the maize nested association mapping (NAM)
      panel to identify lines with significant benzoxazinoid concentrations at later
      developmental stages. At 24 d after imbibition (dai), only three lines, including
      Mo17, showed effective DIMBOA concentrations of 1.5mM or more; B73, by contrast,
      had low a DIMBOA content. Mapping studies based on Mo17 and B73 were performed to
      reveal mechanisms that influence the DIMBOA level in 24 dai plants. A major
      quantitative trait locus mapped to the Bx gene cluster located on the short arm
      of chromosome 4, which encodes the DIMBOA biosynthetic genes. Mo17 was
      distinguished from all other NAM lines by high transcriptional expression of the
      Bx1 gene at later developmental stages. Bx1 encodes the signature enzyme of the
      pathway. In Mo17*B73 hybrids at 24 dai, only the Mo17 Bx1 allele transcript was
      detected. A 3.9kb cis-element, termed DICE (distal cis-element), that is located
      in the Bx gene cluster approximately 140 kb upstream of Bx1, was required for
      high Bx1 transcript levels during later developmental stages in Mo17. The DICE
      region was a hotspot of meiotic recombination. Genetic analysis revealed that
      high 24 dai DIMBOA concentrations were not strictly dependent on high Bx1
      transcript levels. However, constitutive expression of Bx1 in transgenics
      increased DIMBOA levels at 24 dai, corroborating a correlation between DIMBOA
      content and Bx1 transcription.

PMID- 25969553
TI  - Phenotypic and metabolic responses to drought and salinity of four contrasting
      lentil accessions.
AB  - Drought and salinity are among the major abiotic stresses which, often inter
      relatedly, adversely affect plant growth and productivity. Plant stress responses
      depend on the type of stress, on its intensity, on the species, and also on the
      genotype. Different accessions of a species may have evolved different mechanisms
      to cope with stress and to complete their life cycles. This study is focused on
      lentil, an important Mediterranean legume with high quality protein for the human
      diet. The effects of salinity and drought on germination and early growth of
      Castelluccio di Norcia (CAST), Pantelleria (PAN), Ustica (UST), and Eston (EST)
      accessions were evaluated to identify metabolic and phenotypic traits related to
      drought and/or salinity stress tolerance. The results showed a relationship
      between imposed stresses and performance of the cultivars. According to
      germination frequencies, the accession ranking was as follows: NaCl resistant >
      susceptible, PAN > UST > CAST > EST; polyethylene glycol (PEG) resistant >
      susceptible, CAST > UST > EST > PAN. Seedling tolerance rankings were: NaCl
      resistant > susceptible, CAST ~ UST > PAN ~ EST; PEG resistant > susceptible,
      CAST > EST ~ UST > PAN. Changes in the metabolite profiles, mainly quantitative
      rather than qualitative, were observed in the same cultivar in respect to the
      treatments, and among the cultivars under the same treatment. Metabolic
      differences in the stress tolerance of the different genotypes were related to a
      reduction in the levels of tricarboxylic acid (TCA) cycle intermediates. The
      relevant differences, between the most NaCl-tolerant genotype (PAN) and the most
      sensitive one (EST) were related to the decrease in the threonic acid level.
      Stress-specific metabolite indicators were also identified: ornithine and
      asparagine as markers of drought stress and alanine and homoserine as markers of
      salinity stress. 

PMID- 25969554
TI  - Volatile organic compounds as non-invasive markers for plant phenotyping.
AB  - Plants emit a great variety of volatile organic compounds (VOCs) that can
      actively participate in plant growth and protection against biotic and abiotic
      stresses. VOC emissions are strongly dependent on environmental conditions; the
      greatest ambiguity is whether or not the predicted change in climate will
      influence and modify plant-pest interactions that are mediated by VOCs. The
      constitutive and induced emission patterns between plant genotypes, species, and
      taxa are highly variable and can be used as pheno(chemo)typic markers to
      distinguish between different origins and provenances. In recent years
      significant progress has been made in molecular and genetic plant breeding.
      However, there is actually a lack of knowledge in functionally linking genotypes
      and phenotypes, particularly in analyses of plant-environment interactions. Plant
      phenotyping, the assessment of complex plant traits such as growth, development,
      tolerance, resistance, etc., has become a major bottleneck, and quantitative
      information on genotype-environment relationships is the key to addressing major
      future challenges. With increasing demand to support and accelerate progress in
      breeding for novel traits, the plant research community faces the need to measure
      accurately increasingly large numbers of plants and plant traits. In this review
      article, we focus on the promising outlook of VOC phenotyping as a fast and non
      invasive measure of phenotypic dynamics. The basic principle is to define plant
      phenotypes according to their disease resistance and stress tolerance, which in
      turn will help in improving the performance and yield of economically relevant
      plants. 

PMID- 25969555
TI  - Characterization of the promoter and extended C-terminal domain of Arabidopsis
      WRKY33 and functional analysis of tomato WRKY33 homologues in plant stress
      responses.
AB  - Arabidopsis AtWRKY33 plays a critical role in broad plant stress responses.
      Whether there are evolutionarily conserved homologues of AtWRKY33 in other plants
      and what make AtWRKY33 such an important protein in plant stress responses are
      largely unknown. We compared AtWRKY33 with its close homologues to identify
      AtWRKY33-specific regulatory and structural elements, which were then
      functionally analysed through complementation. We also performed phylogenetic
      analysis to identify structural AtWRKY33 homologues in other plants and
      functionally analysed two tomato homologues through complementation and gene
      silencing. AtWRKY33 has an extended C-terminal domain (CTD) absent in its close
      homologue AtWRKY25. Both its CTD and the strong pathogen/stress-responsive
      expression of AtWRKY33 are necessary to complement the critical phenotypes of
      atwrky33. Structural AtWRKY33 homologues were identified in both dicot and
      monocot plants including two (SlWRKY33A and SlWRKY33B) in tomato. Molecular
      complementation and gene silencing confirmed that the two tomato WRKY genes play
      a critical role similar to that of AtWRKY33 in plant stress responses. Thus,
      WRKY33 proteins are evolutionarily conserved with a critical role in broad plant
      stress responses. Both its CTD and promoter are critical for the uniquely
      important roles of WRKY33 in plant stress responses. 

PMID- 25969556
TI  - The genetics of rhizosheath size in a multiparent mapping population of wheat.
AB  - Rhizosheaths comprise soil that adheres to plant roots and, in some species, are
      indicative of root hair length. In this study, the genetics of rhizosheath size
      in wheat was investigated by screening the progeny of multiparent advanced
      generation intercrosses (MAGIC). Two MAGIC populations were screened for
      rhizosheath size using a high throughput method. One MAGIC population was
      developed from intercrosses between four parents (4-way) and the other from
      intercrosses between eight parents (8-way). Transgressive segregation for
      rhizosheath size was observed in both the 4-way and 8-way MAGIC populations. A
      quantitative trait loci (QTL) analysis of the 4-way population identified six
      major loci located on chromosomes 2B, 4D, 5A, 5B, 6A, and 7A together accounting
      for 42% of the variation in rhizosheath size. Rhizosheath size was strongly
      correlated with root hair length and was robust across different soil types in
      the absence of chemical constraints. Rhizosheath size in the MAGIC populations
      was a reliable surrogate for root hair length and, therefore, the QTL identified
      probably control root hair elongation. Members of the basic helix-loop-helix
      family of transcription factors have previously been identified to regulate root
      hair length in Arabidopsis and rice. Since several wheat members of the basic
      helix-loop-helix family of genes are located within or near the QTL, these genes
      are candidates for controlling the long root hair trait. The QTL for rhizosheath
      size identified in this study provides the opportunity to implement marker
      assisted selection to increase root hair length for improved phosphate
      acquisition in wheat.

PMID- 25969557
TI  - Toward production of jet fuel functionality in oilseeds: identification of FatB
      acyl-acyl carrier protein thioesterases and evaluation of combinatorial
      expression strategies in Camelina seeds.
AB  - Seeds of members of the genus Cuphea accumulate medium-chain fatty acids (MCFAs;
      8:0-14:0). MCFA- and palmitic acid- (16:0) rich vegetable oils have received
      attention for jet fuel production, given their similarity in chain length to Jet
      A fuel hydrocarbons. Studies were conducted to test genes, including those from
      Cuphea, for their ability to confer jet fuel-type fatty acid accumulation in seed
      oil of the emerging biofuel crop Camelina sativa. Transcriptomes from Cuphea
      viscosissima and Cuphea pulcherrima developing seeds that accumulate >90% of C8
      and C10 fatty acids revealed three FatB cDNAs (CpuFatB3, CvFatB1, and CpuFatB4)
      expressed predominantly in seeds and structurally divergent from typical FatB
      thioesterases that release 16:0 from acyl carrier protein (ACP). Expression of
      CpuFatB3 and CvFatB1 resulted in Camelina oil with capric acid (10:0), and
      CpuFatB4 expression conferred myristic acid (14:0) production and increased 16:0.
      Co-expression of combinations of previously characterized Cuphea and California
      bay FatBs produced Camelina oils with mixtures of C8-C16 fatty acids, but amounts
      of each fatty acid were less than obtained by expression of individual FatB
      cDNAs. Increases in lauric acid (12:0) and 14:0, but not 10:0, in Camelina oil
      and at the sn-2 position of triacylglycerols resulted from inclusion of a coconut
      lysophosphatidic acid acyltransferase specialized for MCFAs. RNA interference
      (RNAi) suppression of Camelina beta-ketoacyl-ACP synthase II, however, reduced
      12:0 in seeds expressing a 12:0-ACP-specific FatB. Camelina lines presented here
      provide platforms for additional metabolic engineering targeting fatty acid
      synthase and specialized acyltransferases for achieving oils with high levels of
      jet fuel-type fatty acids. 

PMID- 25969558
TI  - Clinical Commentary on "One Mother's Heart Story".

PMID- 25969559
TI  - One Mother's Heart Story.

PMID- 25969560
TI  - Temporal Stability of Molecular Diversity Measures in Natural Populations of
      Drosophila pseudoobscura and Drosophila persimilis.
AB  - Many molecular ecological and evolutionary studies sample wild populations at a
      single point in time, but that data represents genetic variation from a
      potentially unrepresentative snapshot in time. Variation across time in genetic
      parameters may occur quickly in species that produce multiple generations of
      offspring per year. Here, we compare genetic diversity in wild caught populations
      of Drosophila persimilis and Drosophila pseudoobscura collected 16 years apart at
      the same time of year and same site at 4 X-linked and 2 mitochondrial loci to
      assess genetic stability. We found no major changes in nucleotide diversity in
      either species, but we observed a drastic shift in Tajima's D between D.
      pseudoobscura timepoints at 1 locus associated with increased abundance of a set
      of related haplotypes. Our data also suggests that D. persimilis may have
      recently accelerated its demographic expansion. While the changes we observed
      were modest, this study reinforces the importance of considering potential
      temporal variation in genetic parameters within single populations over short
      evolutionary timescales. 

PMID- 25969561
TI  - Comparison of Immunogenicity Between Inactivated and Live Attenuated Hepatitis A
      Vaccines Among Young Adults: A 3-Year Follow-up Study.
AB  - A randomized clinical trial of hepatitis A vaccines (1 or 2 doses of inactivated
      vaccine [Healive] or 1 dose of live attenuated vaccine [Biovac]) was conducted
      among adults to evaluate seroprotection rates and geometric mean concentrations
      of antibody against hepatitis A virus for 36 months. High rates of seroprotection
      persisted for at least 36 months among adults who received 1 or 2 doses of
      inactivated hepatitis A vaccine but not among adults who received 1 dose of live
      attenuated hepatitis A vaccine. The long-term serial monitoring of immunogenicity
      induced by 1 dose of inactivated hepatitis A vaccine is needed to determine an
      effective alternative to a 2-dose schedule. CLINICAL TRIALS REGISTRATION:
      NCT01865968.

PMID- 25969562
TI  - The Rise of Fluoroquinolone-Resistant Escherichia coli in the Community: Scarier
      Than We Thought.

PMID- 25969563
TI  - HIV-1 Infection Accelerates Age According to the Epigenetic Clock.
AB  - BACKGROUND: Infection with human immunodeficiency virus type 1 (HIV) is
      associated with clinical symptoms of accelerated aging, as evidenced by the
      increased incidence and diversity of age-related illnesses at relatively young
      ages and supporting findings of organ and cellular pathologic analyses. But it
      has been difficult to detect an accelerated aging effect at a molecular level.
      METHODS: Here, we used an epigenetic biomarker of aging based on host DNA
      methylation levels to study accelerated aging effects due to HIV infection. DNA
      from brain and blood tissue was assayed via the Illumina Infinium Methylation 450
      K platform. RESULTS: Using 6 novel DNA methylation data sets, we show that HIV
      infection leads to an increase in epigenetic age both in brain tissue (7.4 years)
      and blood (5.2 years). While the observed accelerated aging effects in blood may
      reflect changes in blood cell composition (notably exhausted cytotoxic T cells),
      it is less clear what explains the observed accelerated aging effects in brain
      tissue. CONCLUSIONS: Overall, our results demonstrate that the epigenetic clock
      is a useful biomarker for detecting accelerated aging effects due to HIV
      infection. This tool can be used to accurately determine the extent of age
      acceleration in individual tissues and cells.

PMID- 25969565
TI  - Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell
      lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E
      cadherin.
AB  - OBJECTIVE: Metastasis-associated protein 2 is considered as an intrinsic subunit
      of the nucleosome remodelling and histone deacetylase complex, which contributes
      to the epigenetic silencing genes. More and more evidence suggests that
      metastasis-associated protein 2 is required to maintain the malignant phenotype,
      but the role of metastasis-associated protein 2 function in mediating tumour
      metastasis in non-small-cell lung cancer has not been explored. METHODS:
      Bioinformatics was used to detect the GEO 3141 database, the online tool of
      Kmplot was used to confirm the high expression of metastasis-associated protein 2
      in influencing 5-year overall survival. Wound-healing assay, Transwell invasion
      assay and Living imaging assay together showed that MTA2 shRNA inhibited cell
      migration and invasion in vitro and in vivo. Chromatin immunoprecipitation,
      quantitative chromatin immunoprecipitation and luciferase reporter assays showed
      metastasis-associated protein 2 binding on the promoter of the epithelial
      transmembrane glycoprotein (Ep-CAM) and cell adhesion molecule E-cadherin.
      RESULTS: The patient samples collected in our hospital show that metastasis
      associated protein 2 was expressed in aggressive lung cancer cells, and its
      higher expression is correlated with poor prognosis. Metastasis-associated
      protein 2 promoted cell migration and invasion in vitro and in vivo through
      binding on the promoter of Ep-CAM and E-cadherin. Luciferase reporter assays
      showed repressed or enhanced E-cadherin or Ep-CAM promoter-driven luciferase
      reporter under metastasis-associated protein 2 overexpression or depletion. The
      changes in the level of protein and RNA implied that suppression of downstream E
      cadherin or Ep-CAM was an important mechanism by which metastasis-associated
      protein 2 triggered epithelial-mesenchymal transition and metastasis.
      CONCLUSIONS: Together, our experiments reveal the mechanism for metastasis
      associated protein 2 in facilitating invasive potential of non-small-cell lung
      cancer cells, suggesting that metastasis-associated protein 2 might be a
      potential therapeutic target for treating the metastasis of non-small-cell lung
      cancer.

PMID- 25969566
TI  - Examining trends in the administration of "as needed" medications to inpatients
      with behavioral and psychological symptoms of dementia.
AB  - RATIONALE: The use of "pro re nata" (PRN) medication in patients with behavioral
      and psychological symptoms of dementia (BPSD) is common but may be a source of
      inappropriate medication administration. OBJECTIVE: To identify trends in the
      administration of PRN medications to inpatients with BPSD. METHODS: Retrospective
      chart audits were completed on inpatients with dementia who had PRN medications
      prescribed for aggression, agitation, or insomnia. Data collected included age,
      sex, time of day, day of week, medication used, and dementia diagnosis.
      Additionally, data regarding administration of ranged doses and concurrent use
      with regularly prescribed medications of the same class were collected. RESULTS:
      A total of 170 inpatients with dementia were included. Over 50 346 bed days, 4000
      PRNs were administered. Individuals were more likely to receive a PRN if they
      were younger, shortly after shift change, in the evening, or during the weekend.
      If a ranged dose is provided they are more likely to receive the higher dose. If
      they are receiving regularly scheduled medication from the same class, there is
      risk of double dosing.

PMID- 25969564
TI  - Gut Colonization of Healthy Children and Their Mothers With Pathogenic
      Ciprofloxacin-Resistant Escherichia coli.
AB  - BACKGROUND: The reservoir of pathogenic ciprofloxacin-resistant Escherichia coli
      remains unknown. METHODS: We conducted a prospective cohort study of 80 healthy
      twins and their mothers to determine the frequency of excretion of ciprofloxacin
      resistant, potentially pathogenic E. coli. Stool specimens were cultured
      selectively for ciprofloxacin-resistant gram-negative bacteria. Isolates were
      categorized on the basis of additional resistance and virulence profiles. We also
      prospectively collected clinical metadata. RESULTS: Fifteen children (19%) and 8
      mothers (20%) excreted ciprofloxacin-resistant E. coli at least once. Overall,
      33% of 40 families had at least 1 member whose stool specimen yielded
      ciprofloxacin-resistant E. coli on culture. Fifty-seven submitted stool specimens
      (2.8%) contained such organisms; clones ST131-H30 and ST405 accounted for 52 and
      5 of the positive specimens, respectively. Length of hospital stay after birth (P
      = .002) and maternal colonization (P = .0001) were associated with subsequent
      childhood carriage of ciprofloxacin-resistant E. coli; antibiotic use, acid
      suppression, sex, mode of delivery, and maternal perinatal antibiotic use were
      not. Ciprofloxacin-resistant E. coli were usually resistant to additional
      antibiotic classes, and all had virulence genotypes typical of extraintestinal
      pathogenic E. coli. CONCLUSIONS: Healthy children and their mothers commonly
      harbor ciprofloxacin-resistant E. coli with pathogenic potential.

PMID- 25969567
TI  - Effect of Glycemic Regulation on Endocan Levels in Patients With Diabetes: A
      Preliminary Study.
AB  - Endothelial-specific molecule 1 (endocan) is expressed by endothelial cells and
      may have a major role in the regulation of cell adhesion and in the pathogenesis
      of inflammatory disorders. We aimed to assess change in endocan levels after 3
      months of lifestyle change recommendations and guideline-based treatment.
      Diabetic patients (n = 77) who had neither chronic kidney disease nor chronic
      inflammatory disease were included. After baseline evaluation, the patients were
      advised lifestyle changes, and their medical treatment was determined
      individually according to recommendations of the American Diabetes Association
      (ADA) guidelines. At the end of third month patients were reevaluated. Baseline
      endocan levels were significantly increased in the study group compared with the
      control group. The third-month laboratory workup showed significant reductions in
      hemoglobin A1c, urinary albumin-to-creatinine ratio (UACR), and endocan levels.
      Only delta-UACR was independently correlated with delta-endocan in multivariate
      linear regression analysis. Our findings suggest that serum endocan
      concentrations are elevated in patients with type 2 diabetes and decrease
      following anti-hyperglycemic treatment. Furthermore, decrease in endocan
      concentrations might be associated with improved glycemic control and reductions
      in UACR. 

PMID- 25969568
TI  - Management of Coronary Artery Disease in South Asian Populations: Why and How to
      Prevent and Treat Differently.
AB  - The South Asian (SA) population constitutes one of the largest ethnic groups in
      the world. Several studies that compared host and migrant populations around the
      world indicate that SAs have a higher risk of developing cardiovascular disease
      (CVD) than their native-born counterparts. Herein, we review the literature to
      address the role of the screening tools, scoring systems, and guidelines for
      primary, secondary, and tertiary prevention in these populations. Management
      based on screening for the CVD risk factors in a high-risk population such as SAs
      can improve health care outcomes. There are many scoring tools for calculating 10
      year CVD risk; however, each scoring system has its limitations in this
      particular ethnicity. Further work is needed to establish a unique scoring and
      guidelines in SAs. 

PMID- 25969569
TI  - Takotsubo Cardiomyopathy and Viral Myopericarditis: An Association Which Should
      be Considered in the Differential Diagnosis.

PMID- 25969570
TI  - The role of gabapentin in the management of alcohol withdrawal and dependence.
AB  - OBJECTIVE: To review the literature evaluating gabapentin for alcohol withdrawal
      and dependence. DATA SOURCES: A literature search of MEDLINE (1966 to end of
      March 2015) and PubMed was performed using the terms alcohol, gabapentin,
      withdrawal, and dependence. Additional references were identified from a review
      of literature citations. STUDY SELECTION AND DATA EXTRACTION: English-language
      prospective studies evaluating gabapentin for alcohol withdrawal and dependence
      were evaluated. DATA SYNTHESIS: A total of 10 publications utilizing gabapentin
      in alcohol withdrawal (n = 5) and alcohol dependence (n = 5) were included in
      this review. Limited data suggest that gabapentin can provide benefit in managing
      mild alcohol withdrawal syndrome. There were 5 reported or suspected seizures in
      the withdrawal studies, suggesting that additional safety data are necessary
      before gabapentin monotherapy can be routinely considered. Sleep and mood/anxiety
      related outcomes were positively influenced by gabapentin, which may result in
      long-term benefits if continued beyond the withdrawal period for the treatment of
      alcohol dependence. Studies evaluating gabapentin for alcohol dependence
      demonstrated dose-dependent benefits for complete abstinence, rates of no heavy
      drinking, and cravings. Gabapentin used to treat alcohol dependence was well
      tolerated with no severe adverse reactions reported in the extant literature.
      CONCLUSION: Gabapentin may have a role in the treatment of mild alcohol
      withdrawal, but future studies should focus on adequate dosing strategies.
      Gabapentin should be considered for the treatment of alcohol dependence when
      barriers prevent the use of traditional agents. Additional studies should be
      conducted to further validate findings from the research conducted to date, but
      the current literature is promising for gabapentin in the treatment of alcohol
      dependence.

PMID- 25969571
TI  - Upper Airway Anomalies in Congenital Tracheoesophageal Fistula and Esophageal
      Atresia Patients.
AB  - OBJECTIVE: To examine the prevalence of upper airway anomalies in patients
      diagnosed with congenital tracheoesophageal fistula and esophageal atresia
      (TEF/EA). METHODS: A retrospective review was conducted of all TEF/EA patients
      seen at a tertiary pediatric hospital between January 2008 and December 2013.
      Inclusion criteria included evaluation by the otolaryngology service. Exclusion
      criteria included age>18 years, acquired TEF/EA, subsequent rule out of TEF/EA,
      and otolaryngology evaluation for reasons not pertaining to the airway. Data
      collected and analyzed included demographics, comorbidities, presenting symptoms,
      surgical interventions, laryngoscopic and bronchoscopic examinations, and
      subsequent medical and surgical management. RESULTS: Four hundred and thirty
      patients were diagnosed with TEF/EA at our institution. In all, 32.3%, or 139
      children, were included in the analysis; 56.1% (n=78) male, 43.9% (n=61) female.
      Of the analyzed patients, 4.3% (n=6) were diagnosed with laryngomalacia. Eighteen
      patients (12.9%) were diagnosed with subglottic stenosis. Thirty (21.6%) had
      vocal fold paresis or immobility. Laryngeal cleft was diagnosed in 25.9% (n=36).
      Tracheomalacia was the most common airway finding, diagnosed in 37.4% (n=52)
      patients. CONCLUSION: Patients diagnosed with congenital TEF/EA have a high rate
      of secondary upper airway anomalies. Consideration should be given to perform a
      complete airway evaluation in all of these patients.

PMID- 25969572
TI  - Dyspnea, Dysphonia, and Cough: Varied Presentations of Tracheobronchopathia
      Osteochondroplastica.
AB  - OBJECTIVES: Tracheobronchopathia osteochondroplastica (TPO) is an uncommon,
      benign disease consisting of submucosal, osteocartilaginous nodules that project
      into the tracheal lumen. Far less commonly, these nodules can occur outside the
      tracheal cartilage. This case series discusses the wide range of symptoms and
      treatments of the disease. METHODS: Three patients presented to the laryngology
      clinic with 3 varied presentations of TPO, including dyspnea, dysphonia, and
      cough. These patients were evaluated, subsequently diagnosed with TPO, and
      treated accordingly. RESULTS: Two of the 3 patients presented with extratracheal
      lesions presenting in the cricoid and thyroid cartilages. The patient presenting
      with symptoms of dysphonia was found to have bilateral TPO exclusively within the
      thyroid cartilage, which has never been reported previously. After undergoing a
      partial thyroid cartilage resection removing the bulk of the lesion, the
      patient's symptoms drastically improved. CONCLUSION: While TPO may be a rare
      diagnosis in the general otolaryngologist practice, symptoms frequently bring
      patients into the otolaryngologist's clinic, and an awareness of the disease can
      help minimize unnecessary interventions and allow the surgeon to appropriately
      counsel patients.

PMID- 25969573
TI  - Ponies on Sable Island.

PMID- 25969574
TI  - Paradigm shift: Ideas to reverse a trend.

PMID- 25969575
TI  - An ethicist's commentary on client demands homeopathy.

PMID- 25969576
TI  - Suspected panosteitis in a crossbred calf.
AB  - A male crossbred calf developed a limp and pain upon deep pressure on the right
      hind limb and the right forelimb. The radiographic findings of affected limbs and
      pathological findings of bone biopsy were similar to those observed in canine
      panosteitis. This is the first case of suspected panosteitis reported in cattle. 

PMID- 25969577
TI  - Osteomyelitis associated with Nocardiopsis composta in a dog.
AB  - We report the first detection of Nocardiopsis composta in association with
      osteomyelitis in a young male miniature Australian shepherd dog. Findings
      included suppurative osteomyelitis containing intralesional Fite's acid fast
      bacilli, aerobic culture of branching Gram-positive rods, and positive
      identification via phenotypic analysis and 16S rDNA sequencing. 

PMID- 25969578
TI  - Successful treatment of Corynebacterium urealyticum encrusting cystitis with
      systemic and intravesical antimicrobial therapy.
AB  - A 6-year-old Saint Bernard dog was diagnosed with encrusting cystitis caused by
      Corynebacterium urealyticum. The infection persisted despite the prolonged use of
      antimicrobials and surgical debridement of the urinary bladder. Resolution
      occurred following intravenous vancomycin, urine acidification, and intravesical
      gentamicin. The challenges involved in the treatment of encrusting cystitis are
      described. 

PMID- 25969579
TI  - Pancreatic torsion in a dog.
AB  - A 6-month-old male intact Cane Corso mastiff dog was presented for a recent
      history of vomiting, abdominal pain, and lethargy. A diagnosis of pancreatic
      torsion was made during abdominal exploratory surgery and was confirmed with
      histopathology. The dog underwent partial pancreatectomy and recovered with no
      complications. 

PMID- 25969580
TI  - A high-morbidity outbreak of Johne's disease in game-ranched elk.
AB  - Following an outbreak of Johne's disease on an elk farm in northern Alberta,
      Canada, fecal culture, fecal polymerase chain reaction (PCR), and serum enzyme
      linked immunosorbent assay (ELISA) tests were performed on individual animals.
      The magnitude of the outbreak is described and the challenges associated with
      poor test agreement, as well as herd management options, are discussed. 

PMID- 25969581
TI  - Mannheimia haemolytica vegetative endocarditis in a Suffolk wether.
AB  - A 12-week-old Suffolk wether was diagnosed with bacterial endocarditis associated
      with Mannheimia haemolytica. The wether had shown signs of lethargy, inappetance,
      fever, and a grade 5 of 6 holosystolic murmur. Mannheimia haemolytica was
      cultured from blood premortem and the valvular lesion postmortem. 

PMID- 25969582
TI  - Passive surveillance for ticks on horses in Saskatchewan.
AB  - Passive surveillance of ticks on horses in Saskatchewan revealed that the horses
      were parasitized by 3 species, Dermacentor albipictus, D. andersoni, and D.
      variabilis. The nymphs and adults of D. albipictus occurred on horses earlier in
      the year than did adults of the 2 other species. 

PMID- 25969583
TI  - In vitro evaluation of the impact of silver coating on Escherichia coli adherence
      to urinary catheters.
AB  - A silver-coated urinary catheter was compared to a non-silver-coated urinary
      catheter for the ability to reduce adherence of 6 isolates of Escherichia coli.
      Catheters were incubated with E. coli strains for 0, 24, 48, and 72 h. Broth was
      sampled at all time points to determine CFU/mL. Catheters were subjected to
      sonication to determine adhered bacteria at all time points, and scanning
      electron microscopy (SEM) to semi-quantitatively assess biofilm formation. Silver
      coated catheters had significantly less adhered bacteria than non-silver-coated
      catheters at times 24, 48, and 72 h. Subjectively, silver-coated urinary
      catheters had less biofilm formation than non-silver-coated urinary catheters as
      assessed by SEM. Silver coating of catheters was associated with reduced
      adherence of E. coli in an in vitro evaluation. Testing of catheters in dogs in
      vivo is required to determine if there is a reduction in catheter-associated
      urinary tract infections. 

PMID- 25969584
TI  - Enteric parasites of free-roaming, owned, and rural cats in prairie regions of
      Canada.
AB  - The objective of this study was to determine prevalence, intensity, and zoonotic
      potential of gastrointestinal parasites in free-roaming and pet cats in urban
      areas of Saskatchewan (SK) and a rural region in southwestern Alberta (AB). Fecal
      samples were analyzed using a modified double centrifugation sucrose flotation to
      detect helminth eggs and coccidian oocysts, and an immunofluorescence assay to
      detect Giardia and Cryptosporidium. Endoparasite prevalence was higher in samples
      from rural AB cats (41% of 27) and free-roaming SK cats (32% of 161) than client
      owned SK cats (6% of 31). Parasites identified using morphological and molecular
      techniques included Toxocara cati, Toxascaris leonina, Baylisascaris-type eggs,
      Eucoleus aerophilus, Taenia taeniaeformis, Isospora spp., Cryptosporidium spp.,
      and zoonotic genotype A of Giardia duodenalis. This study demonstrates
      significant differences in endoparasite prevalence in feline populations, and the
      value of molecular techniques in fecal-based surveys to identify and determine
      parasite zoonotic potential. 

PMID- 25969585
TI  - Investigation of biosecurity risks associated with the feed delivery: A pilot
      study.
AB  - This study explored potential biosecurity issues related to the delivery of feed
      to commercial farms. A pilot study was conducted to collect information about the
      day-to-day feed delivery, including biosecurity concerns at the level of the feed
      truck, the driver, and the farm. In addition, a reusable rubber boot was tested
      in an effort to increase the proportion of farms at which truck drivers wore
      clean footwear, and to explore an alternative to the standard plastic disposable
      boots that may be unsafe in winter conditions. Most farms did well in terms of
      proper dead-stock management and keeping the farm lane and feed bin areas clean.
      The provision of reusable rubber boots significantly increased the proportion of
      deliveries in which the driver wore clean footwear. 

PMID- 25969586
TI  - End-stage hypertrophic cardiomyopathy in a cat.
AB  - A 14-year-old Persian cat was referred for evaluation of the progression of
      hypertrophic cardiomyopathy (HCM) after an acute episode of congestive heart
      failure. The diagnosis of HCM had been made almost 13 years ago. Echocardiography
      and electrocardiography revealed end-stage hypertrophic cardiomyopathy and
      multifocal atrial tachycardia. The patient was discharged on medical management
      with a grave prognosis. 

PMID- 25969587
TI  - Where to find Canada's best compensated technicians: Non-DVM wages across the
      nation.

PMID- 25969588
TI  - Remembering Robert Hugh Dunlop: A Canadian giant in veterinary medicine.

PMID- 25969589
TI  - Diagnostic ophthalmology.

PMID- 25969590
TI  - Errata.

PMID- 25969592
TI  - Recovery model of mental illness: a complementary approach to psychiatric care.

PMID- 25969591
TI  - Influence of the built environment on pedestrian route choices of adolescent
      girls.
AB  - We examined the influence of the built environment on pedestrian route selection
      among adolescent girls. Portable global positioning system units, accelerometers,
      and travel diaries were used to identify the origin, destination, and walking
      routes of girls in San Diego, CA and Minneapolis, MN. We completed an inventory
      of the built environment on every street segment to measure the characteristics
      of routes taken and not taken. Route-level variables covering four key conceptual
      built environment domains (Aesthetics, Destinations, Functionality, and Safety)
      were used in the analysis of route choice. Shorter distance had the strongest
      positive association with route choice, while the presence of a greenway or
      trail, higher safety, presence of sidewalks, and availability of destinations
      along a route were also consistently positively associated with route choice at
      both sites. The results suggest that it may be possible to encourage pedestrians
      to walk farther by providing high quality and stimulating routes.

PMID- 25969593
TI  - Tele-Psychiatry: After Mars, Can we Reach the Unreached?

PMID- 25969594
TI  - Indian Psychiatric Society-South Zone: Innovations and Challenges in Providing
      Psychiatric Services to Disadvantaged Populations: A Pilgrim's Progress.

PMID- 25969595
TI  - Delusion of pregnancy: a systematic review of 84 cases in the literature.
AB  - Case reports of delusion of pregnancy have emanated from all over the world, yet
      the rarity of this phenomenology has precluded systematic large scale descriptive
      or cohort studies. This systematic review was conducted to assess the demographic
      characteristics, clinical profile, treatment outcome and aetiological factors
      from the published case reports of delusion of pregnancy. Electronic databases
      including PubMed, PsychInfo and Google Scholar were used to identify case reports
      relating to delusion of pregnancy published in peer-reviewed English language
      journals. All such cases were systematically evaluated by investigators, and
      information was extracted using a structured proforma. A total 40 articles were
      reviewed which included 84 cases. Demographic characteristics revealed that about
      half of the patients were aged 20-40 years. The most common diagnoses were
      schizophrenia (35.7%), bipolar disorders (16.7%) and depression (9.5%). Single
      foetus was reported by 79.8% of the patients, and 45.2% perceived foetal
      movements. Good treatment response was noted in 64.3 % of the cases. The
      prominent aetiological factors that were implicated included psychosocial
      factors, coenaesthopathological processes, socio-cultural factors and
      hyperprolactinaemia. Delusion of pregnancy is a heterogeneous symptom which
      emerges during the course of various neuropsychiatric disorders. A range of
      aetiopathological mechanisms have been implicated in the causation of this
      disorder. 

PMID- 25969596
TI  - Psychiatric and medical disorders in the after math of the uttarakhand disaster:
      assessment, approach, and future challenges.
AB  - PURPOSE: To present the descriptive data on the frequency of medical and
      psychiatric morbidity and also to discuss various pertinent issues relevant to
      the disaster management, the future challenges and psychosocial needs of the 2013
      floods in Uttarakhand, India. MATERIALS AND METHODS: Observation was undertaken
      by the disaster management team of National Institute of Mental Health and
      Neurosciences in the worst affected four districts of Uttarakhand. Qualified
      psychiatrists diagnosed the patients using the International Classification of
      Diseases-10 criteria. Data were collected by direct observation, interview of the
      survivors, group sessions, individual key-informant interview, individual
      session, and group interventions. RESULTS: Patients with physical health problems
      formed the majority of treatment seekers (39.6%) in this report. Only about 2%
      had disaster induced psychiatric diagnoses. As was expected, minor mental
      disorders in the form of depressive disorders and anxiety disorders formed
      majority of the psychiatric morbidity. Substance use disorders appear to be very
      highly prevalent in the community; however, we were not able to assess the
      morbidity systematically. CONCLUSIONS: The mental health infrastructure and
      manpower is abysmally inadequate. There is an urgent need to implement the
      National Mental Health Program to increase the mental health infrastructure and
      services in the four major disaster-affected districts.

PMID- 25969597
TI  - Parkinson's Disease, Depression, and Quality-of-Life.
AB  - BACKGROUND: Depression is the most common psychiatric disorder associated with
      Parkinson's disease (PD) but is often under diagnosed and under treated leading
      to worsening of symptoms and deterioration of the quality-of-life of the people
      suffering from this disease. AIMS: The current study aims to determine the
      correlation between depression and health-related quality-of-life (HRQOL) domains
      in patients with PD. MATERIALS AND METHODS: A sample of 65 consecutive patients
      attending the specialty Parkinson's clinic was assessed by a psychiatrist as part
      of the treatment protocol. Diagnosis of depression was done using the
      International Classification of Diseases-10 by a psychiatrist and depression was
      scored using the Geriatric Depression Scale (GDS). QOL-BREF Malayalam version was
      used to assess quality-of-life in the patients. STATISTICAL ANALYSIS: One-way
      ANOVA was used to find the difference in the quality-of-life experienced by
      different age categories, duration of the disease, psychiatric co-morbidity.
      Independent sample t-test was used to find the difference in the quality-of-life
      experienced by genders, co morbid conditions and to find the difference in the
      scores on GDS and domains of WHO QOL BREF. Association of H and Y staging and
      duration of Parkinsonism with GDS Scores were computed using Pearson's Chi-square
      test. RESULTS AND CONCLUSIONS: There was a significant association of female
      gender and depression with the physical and psychological domains of QOL while
      the duration and staging of PD did not have any association with QOL Domains.
      Depression thus emerges as one of the main predictors of poor quality-of-life in
      PD.

PMID- 25969598
TI  - Issues related to obtaining intelligence quotient-matched controls in autism
      research.
AB  - BACKGROUND: Intelligence Quotient (IQ) is considered to be an index of global
      cognitive functioning and has traditionally been used as a fulcral measure in
      case-control studies in neuro-developmental disorders such as autism. AIM: The
      aim is to highlight the issues of "matching for IQ" with controls in autism
      research. MATERIALS AND METHODS: Percentile scores on the Coloured Progressive
      Matrices of 20 children with autism in the age range of 5 to 12 years have been
      graphically compared with 21 age matched typically developing children. RESULTS
      AND CONCLUSIONS: The percentile scores of the so-called high functioning children
      with autism from special schools were well below that of typically developing
      children. There are many challenges when using IQ in case-control studies of
      autism. Alternative approaches need to be considered.

PMID- 25969599
TI  - Role of lamotrigine augmentation in treatment-resistant obsessive compulsive
      disorder: a retrospective case review from South Asia.
AB  - BACKGROUND: Resistance to pharmacotherapy is one of the major challenges in the
      management of obsessive-compulsive disorder (OCD). OCD being a quite prevalent
      disorder, this resistance adds to the disability. Different strategies are being
      employed to counter this resistance, one of them being augmentation with
      glutamatergic modulators. Lamotrigine is being used for same since the recent
      past with mixed results. OBJECTIVE: The aim was to study the role of lamotrigine
      augmentation in serotonin reuptake inhibitor (SRI) resistant OCD patients.
      METHODOLOGY AND RESULTS: This study was carried by studying the case sheets of
      SRI resistant cases having already completed the treatment. A total of 22 cases
      sheets over 2 years met the study criteria with a mean age of mean age of 34.14
      years. Over a period of 16 weeks, with a mean lamotrigine dose of 150 mg/day, 20
      out of 22 patients had shown a significant response. The mean decrease in Yale
      Brown Obsessive Compulsive Scale score was 67.23% with a baseline score of 28.87.
      There was a similar change on different domains of World Health Organization
      quality of life (P = 0.00564). CONCLUSION: Lamotrigine augmentation to on-going
      treatment with SRIs may be an effective move in case of SRI resistant OCD
      patients.

PMID- 25969600
TI  - Relationship of premenstrual syndrome and premenstrual dysphoric disorder with
      major depression: relevance to clinical practice.
AB  - BACKGROUND: Premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD)
      and depressive disorder are fairly common; symptoms do overlap, often under
      identified and under-emphasized, particularly in rural India. OBJECTIVE: The
      objective was to assess the occurrence of PMS and PMDD in a sample of students
      and staff of a nursing college and to find their correlation with depression.
      MATERIALS AND METHODS: A prospective cohort study; Tertiary Care Hospital in
      Rural India (Wardha, Maharashtra); 118 female nursing students or staff aged
      between 18 and 40 years, who were likely to stay within the institution for the
      study period. The participants were rated on Penn daily symptom report
      prospectively for a period of 3-month. Those who scored positive were applied
      diagnostic and statistical manual of mental disorders, 4(th) edition, text
      revision (DSM-IV TR) criteria for PMDD; and were applied primary care evaluation
      of mental disorders depression screening followed by DSM-IV TR criteria for
      depression. Severity of depression was measured using Hamilton Depression Rating
      Scale. RESULTS: Main outcome measures were frequency and severity of depression
      in individuals with PMS and PMDD and their clinical and sociodemographic
      correlation. The age range of the sample was 18-37 years. Some PMS symptoms were
      observed in 67%; diagnosis of PMDD in 10%; depressive symptoms in 28% of the
      sample. 46.4% of those with depressive symptoms had major depression. The
      diagnosis of major depression was significantly associated with the severity of
      PMS symptoms as well as the presence of PMDD. CONCLUSION: Premenstrual syndrome
      is present in a substantial proportion of young females. Concurrent depression is
      increased by the severity of PMS symptoms and the presence of PMDD. Gynecologist
      needs to screen such subjects for depression and refer to mental-health
      professional early, in routine clinical practice.

PMID- 25969601
TI  - Executive Functions are not Affected by 24 Hours of Sleep Deprivation: A Color
      Word Stroop Task Study.
AB  - BACKGROUND: Sleep is an important factor affecting cognitive performance. Sleep
      deprivation results in fatigue, lack of concentration, confusion and sleepiness
      along with anxiety, depression and irritability. Sleep deprivation can have
      serious consequences in professions like armed forces and medicine where quick
      decisions and actions need to be taken. Color-Word Stroop task is one of the
      reliable tests to assess attention and it analyzes the processing of information
      in two dimensions i.e., reading of words and naming of colour. The evidence
      regarding the effect of sleep deprivation on Stroop interference is conflicting.
      The present study evaluated the effect of 24 hours of sleep deprivation on
      reaction time and interference in Stroop task. MATERIALS AND METHODS: The present
      study was done on 30 healthy male medical student volunteers in the age group of
      18-25 years after taking their consent and clearance from Institute Ethics
      Committee. Recordings of Stroop task were at three times: baseline (between 7-9
      am), after 12 hours (7-9 pm) and after 24 hours (7-9 am, next day). The subjects
      were allowed to perform normal daily activities. RESULTS: The study revealed a
      significant increase in reaction time after 24 hours of sleep deprivation in
      comparison to baseline and after 12 hours of sleep deprivation. There was no
      significant change in interference and facilitation after sleep deprivation in
      comparison to baseline. The number of errors also did not show any significant
      change after sleep deprivation. CONCLUSION: The study indicated that there was
      slowing of responses without change in executive functions after 24 hours of
      sleep deprivation. It is probable that 24 hours of sleep deprivation does not
      bring about change in areas of brain affecting executive functions in healthy
      individuals who have normal sleep cycle. The present study indicated that in
      professions like armed forces and medicine working 24 hours at a stretch can lead
      to decrease in motor responses without affecting information processing and
      judgment ability.

PMID- 25969602
TI  - Assessment of severity of autism using the Indian scale for assessment of autism.
AB  - BACKGROUND: The Indian Scale for Assessment of Autism (ISAA) was developed to
      assess the severity of autism among Indian cases. AIMS: The present study
      evaluated the ISAA in relation to the Childhood Autism Rating Scale (CARS) and
      the Developmental Disability- Children Global Assessment Scale (DD-CGAS).
      MATERIALS AND METHODS: Indian children with ICD 10 diagnoses of Autistic disorder
      (AD, n = 50), Intellectual Disability (ID, n = 50), Attention Deficit
      Hyperactivity Disorder (ADHD, n = 26), other psychiatric disorders (PD-N=25) and
      control children without psychiatric disorders (n = 65) were evaluated using the
      ISAA, DD-CGAS and the CARS (total n = 216). STATISTICAL ANALYSES: In addition to
      descriptive statistics and correlation, analysis of variance (ANOVA) was used to
      assess whether the ISAA scores were significantly different across diagnostic
      groups. RESULTS: Total ISAA scores were significantly higher among children
      diagnosed with autistic disorder compared to four other diagnostic groups. Total
      ISAA scores were significantly correlated with CARS scores and DD-CGAS scores.
      Groups sub-divided on the basis of recommended ISAA cutoff points of severity
      showed significant differences in CARS scores. CONCLUSION: The ISAA can thus be
      used to assess severity of AD among Indian children.

PMID- 25969603
TI  - Oxidative stress during alcohol withdrawal and its relationship with withdrawal
      severity.
AB  - BACKGROUND: Oxidative parameters are altered during alcohol withdrawal and are
      said to contribute towards withdrawal symptoms in alcoholic patients. AIMS: To
      study levels of five selected oxidative parameters during alcohol withdrawal
      state and after treatment of the withdrawal state and to assess the association
      of the oxidative parameters with the severity of alcohol withdrawal. MATERIALS
      AND METHODS: This was a case-control study done in a De-addiction clinic of a
      tertiary teaching centre, Southern India. 50 persons having alcohol withdrawal
      symptoms were included. The oxidative stress parameters malondialdehyde, protein
      carbonyl, glutathione peroxidase, superoxide dismutase and catalase were assessed
      in during the withdrawal phase and again after the withdrawal had subsided. The
      same oxidative stress parameters were measured in the control group. STATISTICAL
      ANALYSIS: Statistical analysis was done using SPSS version 17.0. One way ANOVA
      and Pearson correlation test were used for finding the association between the
      oxidative stress parameters levels and the severity of alcohol withdrawal.
      Multiple linear regression analysis done to predict variables associated with
      level of oxidative parameters. RESULTS: During alcohol withdrawal the pro-oxidant
      malondialdehyde was elevated compared to that in the control group. Among the
      antioxidant enzymes the superoxide dismutase was higher and catalase was lower
      than the control group levels. After remission of the alcohol withdrawal both
      malondialdehyde remained higher and superoxide dismutase lower than in the
      control group. The levels of oxidative stress parameters not correlated with the
      severity of alcohol withdrawal. CONCLUSIONS: oxidative stress parameters show
      changes during alcohol withdrawal and during the remission of withdrawal.
      However, levels of oxidative stress parameters not correlated with the severity
      of withdrawal.

PMID- 25969604
TI  - Mental Illness and Stigma: Has Psychiatry Done more Harm than Good?
AB  - Stigma against people with mental illness is a very complex public health
      problem. There could be diverse reasons for this ranging from: Lack of
      awareness;Fear of a dimly-comprehended and much-misunderstood illness;Illogical
      generalizations; andDisrespect for the heterogeneity of life. The result-for the
      mentally ill-could well be diminished access to social determinants of
      healthcare, employment, and housing. In addition, people with mental illnesses
      are exposed to numerous health risks such as malnutrition, drug abuse, violence
      and homelessness. Maybe this explains nondisclosure of illness in an increasingly
      degenerate civil society. 

PMID- 25969605
TI  - Care giving of people with severe mental illness: an Indian experience.
AB  - BACKGROUND: Caring is a fundamental issue in the rehabilitation of a person with
      mental illness and more so for people with severe mental illness. The lack of
      adequate manpower resources in the country is adding and enlisting the
      responsibility of providing care on the families to provide physical, medical,
      social and psychological care for their severely unwell mentally ill people. AIM
      OF THE STUDY: To examine the load of caregiving with reference to the types of
      care during the symptomatic and remission phases of severe mental illness and the
      various ways in which caregivers adapt their lives to meet the needs of people
      with severe mental illness. MATERIALS AND METHODS: The present research draws its
      data from the 200 families with mental illness in Andra Pradesh and Karnataka in
      India. The data presented in the study was collected from interviews using an
      interview schedule with open-ended questions. RESULTS: The study diffuses the
      notion of 'care' as 'physical', 'medical, 'psychological' and 'social' care. The
      present article focuses on the caregiving roles of the caregivers of people with
      schizophrenia, affective disorders and psychosis not otherwise specified (NOS)
      and found that the caregiving does not differ much between the different
      diagnosis, but caregiving roles changes from active involvement in physical and
      medical care to more of social and psychological care during the remission.
      CONCLUSION: The study records the incredulous gratitude of caregivers at being
      acknowledged for the work they do. In that regard, the study itself provides a
      boost to the morale of tired, unacknowledged caregivers.

PMID- 25969606
TI  - Clinical audit of women with substance use disorders: findings and implications.
AB  - AIM: To examine the socio-demographic, clinical and psychosocial profiles of
      women seeking treatment for substance use disorders (SUDs) in order to understand
      their treatment needs. MATERIALS AND METHODS: The psychiatric case records of 40
      women with SUDs who sought consultation between the year 2012 and 2013 were
      analysed. RESULTS: The mean age of the sample was 38 years (standard deviation,
      S.D = +/- 7.24). Among these, 52.5% were married and 30% were separated or
      divorced. Mean age of onset of substance dependence was 28.68 years (S.D. = +/-
      7.02) with an average of 9.65 years (S.D = +/- 7.69) of dependence. Alcohol
      dependence was present in 80% of the patients, followed by nicotine dependence in
      54% of the patients. Co-morbid Axis I and Axis II disorders were present in 62.5%
      and 10% of the patients respectively. Childhood adverse experiences such as abuse
      and neglect were reported by 20% of the patients. The factors contributing to
      initiation and maintenance of substance use were marital discord and
      interpersonal conflicts (70%), influence of significant others (66%), death of a
      family members (10%) and other stressful life events (25%). Major consequences of
      substance use were substance-induced physical problems (62.5%) and interpersonal
      conflicts (40%). Data analysis indicated poor follow up and relapse rate of 50%.
      CONCLUSIONS: Adverse life events and interpersonal conflicts are significant
      contributing factors to substance use among women. The study has implications for
      planning gender sensitive, multi-dimensional treatment programmes for women
      seeking treatment for SUDs in India.

PMID- 25969607
TI  - Comparison of the Diagnostic Accuracy and Validity of a Short Version of Teen
      Screen Questionnaire-Mental Health (TSQ -M-Short) for Use in Community.
AB  - BACKGROUND: A few self-administered questionnaires are available for assessing
      mental health among adolescents in primary-care settings. Brief measures are
      desirable for use in big-data, epidemiological studies. OBJECTIVES: To evaluate a
      7-item version, of the Teen Screen Questionnaire-Mental Health (TSQ-M), the TSQ-M
      Short. MATERIALS AND METHODS: In this prospective cross-sectional study of 140
      adolescents, recruited from 6 rural or urban schools, the newly developed TSQ-M
      Short as the measure for validation and General Health Questionnaire-12 item (GHQ
      12) as the gold standard measure were administered by independent trained raters.
      Tests for diagnostic accuracy and validity were conducted. RESULTS: A total TSQ-M
      Short score of >= 6 had a sensitivity of 76%, specificity of 74%, positive
      likelihood ratio of 2.99, negative likelihood ratio of 0.33, positive predictive
      value of 6% and a negative predictive value of 82.1%. The area under curve (AUC)
      in the Receiver Operating Characteristic (ROC) for the TSQ-M-Short version was
      0.84 (95% cumulative incidence (CI) = 0.76-0.89). The AUC for the TSQ-M-Short
      version was higher than the AUC for the original version, and the difference
      between the areas was 0.10 (95% CI = 0.02-0.19), which was statistically
      significant (z = 2.49; P = 0.01). The internal consistency of TSQ-M-Short, as
      measured by chronbach's alpha, was 0.34 (95% CI = 0.15-0.48). The construct
      validity demonstrated a 3-factor structure, which explained 55% of the variance.
      CONCLUSION: The TSQ-M-Short has an overall diagnostic accuracy which is better
      than the original TSQ-M. Although the original version includes symptoms for more
      mental health disorders, providing a wider screen. This short version will prove
      useful in big-data studies.

PMID- 25969608
TI  - Neuropsychological assessment in obsessive-compulsive disorder.
AB  - BACKGROUND: Neuropsychological deficits in obsessive-compulsive disorder (OCD)
      have been encouraged by brain imaging studies suggesting a putative fron to-
      striatial biological basis of the condition. Studies of neuropsychological
      functions in OCD have documented deficits in several cognitive domains,
      particularly with regard to visuospatial abilities, executive functioning, motor
      speed and memory. The Aim of the present study was to assess neuropsychological
      profile of patients with OCD. Objectives of the study were to assess and compare
      the neuropsychological profile of patients with OCD and matched healthy controls.
      MATERIALS AND METHODS: Twenty clinically stable outpatients with ICD-10 diagnosis
      of OCD and equal number of normal controls matched for age, education, gender and
      handedness were studied using a battery of neuropsychological tests. The tests
      consisted of verbal and performance tests of intelligence, memory, perceptual
      motor functions, set test and Wisconsin Card Sorting Test (WCST). RESULTS: On
      perceptual-motor functions, verbal fluency, executive functions (WCST),
      intelligence and memory patients with OCD did not show impairments comparable to
      healthy controls. An attempt to correlate the test findings with the duration of
      illness, stability of illness and the average drug dose was made and it was found
      that there was no correlation between the two. CONCLUSION: The present study does
      not provide evidence for a localized neuropsychological/cognitive impairment in
      OCD in cases that are stable for at least three months. Absence of impairments in
      perceptual-motor functions, verbal fluency, executive functions (WCST),
      intelligence, and memory does not agree with the results of other studies using
      these tests.

PMID- 25969609
TI  - Asperger syndrome in India: findings from a case-series with respect to clinical
      profile and comorbidity.
AB  - Asperger syndrome (AS) is an autism spectrum disorder with a high rate of
      psychiatric comorbidity. We describe the clinical profile and psychiatric
      comorbidity in a series of affected individuals referred to an Indian general
      hospital psychiatry setting. Gilliam Asperger's disorder scale was used to
      evaluate the clinical characteristics while Mini-International Neuropsychiatric
      Interview (MINI)-KID and MINI-PLUS were used to assess psychiatric comorbidity.
      The profile of subjects with AS in our case-series appears similar to that
      published elsewhere with high rates of psychiatric comorbidity. Mental health
      professionals should evaluate for psychiatric comorbidity in individuals with
      autism spectrum disorders. 

PMID- 25969610
TI  - The mental health care bill 2013: a critical appraisal.
AB  - The Mental Health Care Bill - 2013 has been introduced in Rajya Sabha and is now
      waiting for enactment. The Bill entails unprecedented measures to be undertaken
      by the Government ensuring everyone right to access mental health care and
      treatment from services run or funded by the Government. The Government is to
      meet the man-power requirement of mental health professionals according to
      international standard within a period of ten years. Various rights of persons
      with mental illness have been ensured. All the places where psychiatric patients
      are admitted and treated including the general hospital psychiatry units (GHPU)
      are to be registered as mental health establishments. Unmodified ECT has been
      banned and ECT to minors can be given only after approval from the Mental Health
      Review Board. This article advocates for exemption of GHPU from the purview of
      the Bill, taking into consideration impediment created in the treatment of vast
      majority of psychiatric patients who retain their insight into the illness and
      seldom require involuntary admissions. It is also advocated to reconsider ban on
      unmodified ECT and restriction placed on ECT to minor which are very effective
      treatment methods based on scientific evidence. In our country, family is an
      important asset in management of mental illness. But requirement of seeking
      approval from the Board in many of the mental health care decision may discourage
      the families to be proactive in taking care of their wards. The Board and Mental
      Health Authorities at the central and the state levels are authorized to take
      many crucial decisions, but these panels have very few experts in the field of
      mental health. 

PMID- 25969611
TI  - An adverse drug interaction of haloperidol with levodopa.
AB  - Drug interactions are known to play a significant role in the incidence of
      adverse drug reactions (ADRs) both in the community and in hospitals. Both the
      newer atypical antipsychotics and their more traditional counterparts are subject
      to drug - drug interactions amongst themselves, with other psychotropics, and
      with the agents used in the treatment of various physical ailments. The most
      common interactions encountered in clinical practice are pharmacodynamic in
      nature. It is well established that antipsychotic drugs reduce the efficacy of
      levodopa in parkinson's disease by blockade of dopamine receptors in the corpus
      striatum. The case reported here illustrates a common pharmacodynamic drug
      interaction of haloperidol with levodopa in a 60-year-old female patient. 

PMID- 25969612
TI  - Tourette syndrome and bipolar disorder: unique problems with pediatric
      comorbidity.
AB  - Tourette syndrome and bipolar disorder are frequent comorbidities in pediatric
      age group. They provide a clinician with certain unique challenges. While on one
      hand the tics mask manifestation of affective symptomatology, the latter makes it
      difficult to elicit tics with certainty. Data suggest that they might share
      genetic and neurobiological basis and this is currently an area of extensive
      research. These clinical and biological overlaps provide grey areas in our
      understanding, which not only complicates the diagnosis, but also poses problems
      with management. 

PMID- 25969613
TI  - An extremely rare association of dyggve-melchior-clausen syndrome with mania:
      coincidence or comorbidity.
AB  - Dyggve-Melchior-Clausen syndrome is a progressive spondylo-epi-metaphyseal
      dysplasia associated with mental retardation, characterized by a triad of
      skeletal deformities (short trunk dwarfism, scoliosis, microcephaly, and limb
      deformities), facial dysmorphism, and intellectual disability. It an extremely
      rare condition. Till now, there was no evidence of association of Dyggve-Melchior
      Clausen Syndrome with mood disorder. This case report highlights the extremely
      rare association of Dyggve-Melchior-Clausen syndrome with bipolar affective
      disorder. The patient had responded well to the combination of mood stabilizer
      and antipsychotics (sodium valproate and risperidone). To the best of author's
      knowledge, this is the first case report depicting such association. Both Dyggve
      Melchior-Clausen syndrome and bipolar affective disorder are associated with 18q
      chromosome. This background information raises the possibility of co-morbid
      association of two disorders rather than a chance association due to genetic
      linkage. 

PMID- 25969614
TI  - Obsessive compulsive disorder in a 4-year-old child.
AB  - Obsessive-compulsive disorder (OCD) is a very distressing disorder for both
      patient and caregiver. Usual onset of the disorder is in late second or early
      third decade of life. It is diagnosed in children but rarely before 5 years. A
      case of OCD in a 4-year-old girl is reported here. Diagnostic and therapeutic
      dilemmas in such a situation are discussed. 

PMID- 25969615
TI  - Psychological autopsy and necropsy of an unusual case of suicide by intravenous
      toluene.
AB  - Toluene (methylbenzene; volatile hydrocarbon) is an industrial solvent that
      causes major injury to the lungs; the organ being the first capillary bed
      encountered. We report an unusual case of suicide by a 24-year-old male,
      paramedical professional, with fatal outcome within 16 h of intentional,
      intravenous self-administration of toluene, with clinical presentation of acute
      respiratory distress syndrome. Psychological autopsy revealed severe depressive
      disorder and solvent (inhalant) abuse, with marital disharmony as the
      precipitating stressor for suicide. Necropsy revealed diffuse congestion of
      internal organs like lungs and liver, epicardial petechial hemorrhages, and
      gastric hemorrhages. Treatment of toluene poisoning includes supportive care as
      no specific antidote is available. Early and aggressive management may be
      conducive to a favorable outcome with minimal residual pulmonary sequelae.
      Relevant literature of toluene poisoning was identified via PubMed, PubChem,
      ToxNet, Hazardous Substances Data Bank (HSDB), Embase, and PsycINFO. To our
      knowledge, this is the first case of suicide by intravenous administration of
      toluene in the literature. 

PMID- 25969616
TI  - Case report on anorexia nervosa.
AB  - Anorexia nervosa is an eating disorder characterized by excessive restriction on
      food intake and irrational fear of gaining weight, often accompanied by a
      distorted body self-perception. It is clinically diagnosed more frequently in
      females, with type and severity varying with each case. The current report is a
      case of a 25-year-old female, married for 5 years, educated up to 10(th)
      standard, a homemaker, hailing from an upper social class Hindu (Marvadi) family,
      living with husband's family in Urban Bangalore; presented to our tertiary care
      centre with complaints of gradual loss of weight, recurrent episodes of vomiting,
      from a period of two years, menstrual irregularities from 1 year and amenorrhea
      since 6 months, with a probable precipitating factor being husband's critical
      comment on her weight. Diagnosis of atypical anorexia nervosa was made, with the
      body mass index (BMI) being 15.6. A multidisciplinary therapeutic approach was
      employed to facilitate remission. Through this case report the authors call for
      the attention of general practitioners and other medical practitioners to be
      aware of the symptomatology of eating disorders as most patients would overtly
      express somatic conditions similar to the reported case so as to facilitate early
      psychiatric intervention. 

PMID- 25969617
TI  - Psychiatric manifestation of chronic subdural hematoma: the unfolding of mystery
      in a homeless patient.
AB  - The clinical manifestation of chronic subdural hematoma is not limited to
      neurological deficits or cognitive impairment. It may present with behavioral
      abnormalities. When the behavioral abnormalities present without obvious
      neurological deficits and in the absence of trauma, it leads to misdiagnosis. A
      trivial trauma may cause intracranial bleed that is either missed or ignored in
      the clinical history. This case report highlights the clinical picture of a
      homeless patient who presented with withdrawn and disorganized behavior, apathy
      and poverty of speech in the absence of any neurological deficit. His clinical
      presentation led to a possibility of psychosis and he was started on
      antipsychotics. He had developed extrapyramidal side effects in low dose of
      antipsychotic without any clinical benefit in his clinical picture. Neuroimaging
      done to rule out any possible organicity-revealed bilateral subdural hematoma,
      which was later evacuated by neurosurgical intervention in multiple settings and
      the patient had improved. This case report unfolds the mystery behind the
      psychotic presentation in a homeless adult. 

PMID- 25969618
TI  - Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it
      Inflammation Mediated?
AB  - Lyme disease has been reported to be associated with various psychiatric
      presentations. Borreliaburgdorferi (Bb) can present with symptoms similar to
      schizophrenia and bipolar disorder. It has been suggested that inflammation
      incurred during the Bb infection leads to neurodegenerative changes that result
      in schizophrenia-like presentations. We report a case of a 41-year-old male with
      a past history of Bb infection who presents with psychosis. Later in the course
      of his hospitalization, he developed mood symptoms and was diagnosed with
      schizoaffective disorder, bipolar type. This case highlights the diagnosis and
      treatment of a patient with the unique presentation of schizoaffective disorder,
      bipolar type in the setting of previous Bb infection. 

PMID- 25969619
TI  - Sustained Ventricular Tachycardia after Electroconvulsive Therapy: Can it be
      Prevented?

PMID- 25969620
TI  - Impact factor: the holy grail of research.

PMID- 25969621
TI  - Venlafaxine-induced severe sleep bruxism in a patient with generalized anxiety
      disorder.

PMID- 25969622
TI  - Polarity Index: A Novel Bipolar Metric: Is it Clinically Useful?

PMID- 25969623
TI  - Beauvoir and demystifying paradoxical characteristics of narcissistic personality
      disorder.

PMID- 25969624
TI  - Clozapine induced supra ventricular tachycardia.

PMID- 25969627
TI  - Mediators of gut mucosal immunity and inflammation.

PMID- 25969626
TI  - Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and
      Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages.
AB  - Reactive oxygen species (ROS) and oxidative stress are thought to play a central
      role in potentiating macrophage activation, causing excessive inflammation,
      tissue damage, and sepsis. Recently, we have shown that punicalagin (PUN)
      exhibits anti-inflammatory activity in LPS-stimulated macrophages. However, the
      potential antioxidant effects of PUN in macrophages remain unclear. Revealing
      these effects will help understand the mechanism underlying its ability to
      inhibit excessive macrophage activation. Hemeoxygenase-1 (HO-1) exhibits
      antioxidant activity in macrophages. Therefore, we hypothesized that HO-1 is a
      potential target of PUN and tried to reveal its antioxidant mechanism. Here, PUN
      treatment increased HO-1 expression together with its upstream mediator nuclear
      factor-erythroid 2 p45-related factor 2 (Nrf2). However, specific inhibition of
      Nrf2 by brusatol (a specific Nrf2 inhibitor) dramatically blocked PUN-induced HO
      1 expression. Previous research has demonstrated that the PI3K/Akt pathway plays
      a critical role in modulating Nrf2/HO-1 protein expression as an upstream
      signaling molecule. Here, LY294002, a specific PI3K/Akt inhibitor, suppressed PUN
      induced HO-1 expression and led to ROS accumulation in macrophages. Furthermore,
      PUN inhibited LPS-induced oxidative stress in macrophages by reducing ROS and NO
      generation and increasing superoxide dismutase (SOD) 1 mRNA expression. These
      findings provide new perspectives for novel therapeutic approaches using
      antioxidant medicines and compounds against oxidative stress and excessive
      inflammatory diseases including tissue damage, sepsis, and endotoxemic shock. 

PMID- 25969625
TI  - Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated
      Interferon-alpha Based Therapy.
AB  - Pegylated-interferon-alpha based therapy for the treatment of chronic hepatitis C
      (CHC) is considered suboptimal as not all patients respond to the treatment and
      it is associated with several side effects that could lead to dose reduction
      and/or termination of therapy. The currently used markers to monitor the response
      to treatment are based on viral kinetics and their performance in the prediction
      of treatment outcome is moderate and does not combine accuracy and their values
      have several limitations. Hence, the development of new sensitive and specific
      predictor markers could provide a useful tool for the clinicians and healthcare
      providers, especially in the new era of interferon-free therapy, for the
      classification of patients according to their response to the standard therapy
      and only subscribing the novel directly acting antiviral drugs to those who are
      anticipated not to respond to the conventional therapy and/or have absolute
      contraindications for its use. The importance of activins and follistatin in the
      regulation of immune system, liver biology, and pathology has recently emerged.
      This review appraises the up-to-date knowledge regarding the role of activins and
      follistatin in liver biology and immune system and their role in the
      pathophysiology of CHC. 

PMID- 25969628
TI  - Decreased IL-27 Negatively Correlated with Th17 Cells in Non-Small-Cell Lung
      Cancer Patients.
AB  - The presence of Th17 cells and IL-27 is observed in a variety of inflammatory
      associated cancers. However, there are some data on the role of Th17 cells and IL
      27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC).
      The aim of this study is to assess the variation of Th17 cells and IL-27 in the
      peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in
      peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The
      serum concentrations of IL-27 and IL-17 were measured by enzyme-linked
      immunosorbent assay (ELISA). The mRNA expression of RORgammat and IL-27 in the
      peripheral blood was examined by real-time quantitative polymerase chain reaction
      (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal
      controls. The frequency of Th17 cells was increased in NSCLC patients,
      accompanied by the upregulation of IL-17 and RORgammat. IL-27 negatively
      correlated with the number of Th17 cells and the RORgammat mRNA. Our results
      indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and
      better understanding of the regulatory effects of IL-27 on Th17 cells may shed
      light on potential new targets in cancer prevention and therapy. 

PMID- 25969629
TI  - Social networks en passant.

PMID- 25969630
TI  - Presidential address.

PMID- 25969631
TI  - Imaging in oncology: Recent advances.

PMID- 25969633
TI  - Post-treatment imaging of high-grade gliomas.
AB  - Current standard of care for treatment of newly diagnosed high grade gliomas is
      surgery followed by concomitant radiotherapy (RT) and chemotherapy (CT) with
      temozolomide (TMZ). Recently, bevacizumab, an anti - angiogenic agent has also
      been approved for treatment of recurrent gliomas. Baseline imaging after excision
      is optimally obtained in the first 24 hours. When baseline postoperative imaging
      is delayed beyond 24 hours, subacute hemorrhage, subacute ischemia and
      inflammation at the resection margins render differentiation from residual tumor
      challenging. Radiation necrosis is a well recognized entity and is differentiated
      from recurrence based on morphology on structural imaging, presence of lipid -
      lactate complexes with lack of choline on spectroscopy and low normalized
      cerebral blood volume (CBV) ratios at perfusion imaging. Novel chemotherapies
      have lead to the occurrence of interesting but sometimes confusing post treatment
      imaging appearances including the phenomena of 'pseudoprogression' and
      'pseudoresponse'. Pseudoprogression refers to transient, self resolving focal
      enhancement mediated by TMZ-induced increased vascular permeability and local
      inflammatory response. Pathologically, these lesions do not have viable tumor.
      The lesions stabilize or regress without further treatment and are usually
      clinically asymptomatic. Pseudoresponse refers to rapid regression of
      enhancement, perfusion, mass effect and midline shift caused by the anti -
      angiogenic effect of bevacizumab. It is termed pseudoresponse since biological
      tumor persists as non-enhancing altered signal. It is important for radiologists
      to be aware of these entities seen on post treatment imaging of gliomas, as
      misinterpretation may lead to inappropriate management decisions and
      prognostication. 

PMID- 25969632
TI  - Appropriateness criteria of FDG PET/CT in oncology.
AB  - (18)Fluorine-2-fluoro-2-Deoxy-d-glucose ((18)F-FDG) positron emission
      tomography/computerized tomography (PET/CT) is a well-established functional
      imaging method widely used in oncology. In this article, we have incorporated the
      various indications for (18)FDG PET/CT in oncology based on available evidence
      and current guidelines. Growing body of evidence for use of (18)FDG PET/CT in
      select tumors is also discussed. This article attempts to give the reader an
      overview of the appropriateness of using (18)F-FDG PET/CT in various
      malignancies. 

PMID- 25969634
TI  - Imaging of lung cancer: Implications on staging and management.
AB  - Lung cancer is one of the leading causes of cancer-related deaths. Accurate
      assessment of disease extent is important in deciding the optimal treatment
      approach. To play an important role in the multidisciplinary management of lung
      cancer patients, it is necessary that the radiologist understands the principles
      of staging and the implications of radiological findings on the various staging
      descriptors and eventual treatment decisions. 

PMID- 25969635
TI  - Imaging for assessment of treatment response in hepatocellular carcinoma: Current
      update.
AB  - Morphologic methods such as the Response Evaluation Criteria in Solid Tumors
      (RECIST) are considered as the gold standard for response assessment in the
      management of cancer. However, with the increasing clinical use of antineoplastic
      cytostatic agents and locoregional interventional therapies in hepatocellular
      carcinoma (HCC), conventional morphologic methods are confronting limitations in
      response assessment. Thus, there is an increasing interest in new imaging methods
      for response assessment, which can evaluate tumor biology such as vascular
      physiology, fibrosis, necrosis, and metabolism. In this review, we discuss
      various novel imaging methods for response assessment and compare them with the
      conventional ones in HCC. 

PMID- 25969636
TI  - Imaging in neuroblastoma: An update.
AB  - Neuroblastoma is the third common tumor in children. Imaging plays an important
      role in the diagnosis, staging, treatment planning, response evaluation and in
      follow-up of a case of Neuroblastoma. The International Neuroblastoma Risk Group
      task force has recently introduced an imaging-based staging system and laid down
      guidelines for uniform reporting of imaging studies. This review is an update on
      imaging in neuroblastoma, with emphasis on these guidelines. 

PMID- 25969637
TI  - Imaging in endometrial carcinoma.
AB  - Endometrial carcinoma (EC) is the most common gynecologic malignancy in the
      United States. Prognosis depends on patient age, histological grade, depth of
      myometrial invasion and/or cervical invasion, and the presence of lymph node
      metastases. Although EC is staged surgically according to the International
      Federation of Gynecology and Obstetrics (FIGO) system, preoperative imaging can
      assist in optimal treatment planning. Several imaging techniques such as
      transvaginal ultrasonography (TVUS), computed tomography (CT), and magnetic
      resonance imaging (MRI) have been used as diagnostic tools for preoperative
      staging of EC. Recently, positron emission tomography (PET), PET/CT, and PET/MRI
      have also been used in staging these patients. In this article, we review the
      value of imaging in diagnosis, staging, treatment planning, and detection of
      recurrent disease in patients with EC. 

PMID- 25969638
TI  - Imaging in rectal cancer with emphasis on local staging with MRI.
AB  - Imaging in rectal cancer has a vital role in staging disease, and in selecting
      and optimizing treatment planning. High-resolution MRI (HR-MRI) is the
      recommended method of first choice for local staging of rectal cancer for both
      primary staging and for restaging after preoperative chemoradiation (CT-RT). HR
      MRI helps decide between upfront surgery and preoperative CT-RT. It provides high
      accuracy for prediction of circumferential resection margin at surgery, T
      category, and nodal status in that order. MRI also helps assess resectability
      after preoperative CT-RT and decide between sphincter saving or more radical
      surgery. Accurate technique is crucial for obtaining high-resolution images in
      the appropriate planes for correct staging. The phased array external coil has
      replaced the endorectal coil that is no longer recommended. Non-fat suppressed 2D
      T2-weighted (T2W) sequences in orthogonal planes to the tumor are sufficient for
      primary staging. Contrast-enhanced MRI is considered inappropriate for both
      primary staging and restaging. Diffusion-weighted sequence may be of value in
      restaging. Multidetector CT cannot replace MRI in local staging, but has an
      important role for evaluating distant metastases. Positron emission tomography
      computed tomography (PET/CT) has a limited role in the initial staging of rectal
      cancer and is reserved for cases with resectable metastatic disease before
      contemplating surgery. This article briefly reviews the comprehensive role of
      imaging in rectal cancer, describes the role of MRI in local staging in detail,
      discusses the optimal MRI technique, and provides a synoptic report for both
      primary staging and restaging after CT-RT in routine practice. 

PMID- 25969639
TI  - Role of dynamic CT perfusion study in evaluating various intracranial space
      occupying lesions.
AB  - AIMS: Differentiating intracranial mass lesions on CT scan is challenging. The
      purpose of our study was to determine the perfusion parameters in various
      intracranial space-occupying lesions (ICSOL), differentiate benign and malignant
      lesions, and differentiate between grades of gliomas. MATERIALS AND METHODS: We
      performed CT perfusion (CTP) in 64 patients, with age ranging from 17 to 68
      years, having space-occupying lesions in brain and calculated relative cerebral
      blood flow (rCBF) and relative cerebral blood volume (rCBV). RESULTS: We found
      significantly lower perfusion in low-grade gliomas as compared to high-grade
      tumors, lymphoma, and metastases. Similarly in infective lesions, TWT and
      abscesses showed significantly lower perfusion compared to TOT. In ring enhancing
      lesions, capsule of TWT showed significantly lower perfusion as compared to
      abscesses, TOT, and metastases. CONCLUSION: Thus, in conclusion, infective
      lesions can be differentiated from tumors like lymphomas, high-grade gliomas, or
      metastases based on perfusion parameters. The cut off value of rCBV 1.64 can be
      used to differentiate between low grade and high grade gliomas. However,
      depending only on perfusion parameters, differentiation between the tumors like
      lymphomas, high-grade gliomas, and metastases may not be possible.

PMID- 25969640
TI  - Morphometric analysis of diameter and relationship of vertebral artery with
      respect to transverse foramen in Indian population.
AB  - PURPOSE: To study the location, origin, size and relationship of the vertebral
      artery and the transverse foramina in the lower cervical spine by computed
      tomographic angiography (CTA) measurements in the Indian population. MATERIALS
      AND METHODS: A retrospective review of multi-detector CT (MDCT) cerebral
      angiography scans was done between June 2011 and February 2014. A total of 120
      patients were evaluated. The diameter of the vertebral artery (AL) and the
      shortest distance between the vertebral artery and the medial (M), lateral (L),
      anterior (A), and posterior (P) borders of transverse foramen were studied. In
      addition, the shortest distance between the vertebral artery and pedicle (h) was
      also analyzed. STATISTICAL ANALYSIS: The means and their standard deviations (SD)
      were calculated in both the sexes. The t-tests were performed to look for
      significant sexual difference. RESULTS: The largest vertebral artery diameter
      (AL) was at level C7 on the right side (3.5 +/- 0.8) and at the level of C5 on
      the left side (3.7 +/- 0.4). Statistically significant difference between males
      and females were seen at levels C4, C5, and C7. The diameter of the vertebral
      artery was smaller in females than males. The L value was greater than other
      parameters (M, A, P) at the same level in all the measurements. The h value was
      greatest at C6 level and shortest at C5. CONCLUSION: CTA is necessary before
      pedicle screw fixation due to variation in measurements at all levels. The
      highest potential risk of vertebral artery injury during cervical pedicle screw
      implantation may be at C5, then at C4, and the safest is at C7.

PMID- 25969641
TI  - Can sonographic measurement of optic nerve sheath diameter be used to detect
      raised intracranial pressure in patients with tuberculous meningitis? A
      prospective observational study.
AB  - CNS Tuberculosis can manifest as meningitis, arachnoiditis and a tuberculoma. The
      rupture of a tubercle into the subarachnoid space leads to Tuberculosis
      Meningitis (TBME); the resulting hypersensitivity reaction can lead to an
      elevation of the intracranial pressure and hydrocephalus. While bedside optic
      nerve sheath diameter (ONSD) ultrasonography (USG) can be a sensitive screening
      test for elevated intracranial pressure in adult head injury, little is known
      regarding ONSD measurements in Tuberculosis Meningitis. OBJECTIVES: The aim of
      this study was to determine whether patients with TBME had dilation of the optic
      nerve sheath, as detected by ocular USG performed in the emergency department
      (ED). MATERIALS AND METHODS: We conducted a prospective, observational study on
      adult ED patients with suspected TBME. Patients underwent USG measurements of the
      optic nerve followed by MRI. The ONSD was measured 3 mm behind the globe in each
      eye. MRI evidence of basilar meningeal enhancement and any degree of
      hydrocephalus was suggestive of TBME. Those patients without evidence of
      hydrocephalus subsequently underwent a lumbar puncture to confirm the diagnosis.
      Exclusion criteria were age less than 18 and obvious ocular pathology. In total,
      the optic nerve sheath diameters of 25 adults with confirmed TBME were measured.
      These measurements were compared with 120 control patients. RESULTS: The upper
      limit of normal ONSD was 4.37 mm in control group. Those patients with TBME had a
      mean ONSD of 5.81 mm (SD 0.42). These results confirm that patients with
      tuberculosis meningitis have an ONSD in excess of the control data (P < 0.001).
      CONCLUSION: The evaluation of the ONSD is a simple non-invasive and potentially
      useful tool in the assessment of adults suspected of having TBME.

PMID- 25969642
TI  - Osmotic myelinolysis: Does extrapontine myelinolysis precede central pontine
      myelinolysis? Report of two cases and review of literature.
AB  - Osmotic myelinolysis is an acute, rare, demyelinating process. After the initial
      description of the condition by Adam and colleagues in 1959, many case series
      have been published describing the central and extrapontine myelinolysis. Imaging
      has a definitive role in establishing the diagnosis of osmotic myelinolysis in
      vivo and diffusion-weighted imaging reveals earliest changes in affected brain
      parenchyma. We report two cases of patients with proven malignancy who developed
      extrapontine myelinolysis after treatment for hyponatremia and progressed to
      central pontine myelinolysis within a week. This was confirmed with magnetic
      resonance (MR) imaging and clinical assessment. This temporal progression of MR
      features, especially on diffusion-weighted imaging, from extrapontine to central
      pontine myelinolysis in osmotic injury has not been described in literature to
      the best of our knowledge. An early MRI of the brain in suspected/high-risk cases
      of osmotic myelinolysis may show features of extrapontine myelinolysis in the
      form of restricted diffusion in bilateral basal ganglia and may serve as a guide
      for predicting progression, prognosticating and deciding further treatment of
      pontine myelinolysis. We propose that in a significant number of cases, central
      pontine myelinolysis may be predicted by doing an early MRI of the brain with
      diffusion-weighted imaging, when extrapontine symptoms start to develop. This can
      potentially increase the window period and possibilities for therapeutic
      intervention and may even help in prevention. 

PMID- 25969643
TI  - Hilar cholangiocarcinoma: Cross sectional evaluation of disease spectrum.
AB  - Although hilar cholangiocarcinoma is relatively rare, it can be diagnosed on
      imaging by identifying its typical pattern. In most cases, the tumor appears to
      be centered on the right or left hepatic duct with involvement of the ipsilateral
      portal vein, atrophy of hepatic lobe on that side, and invasion of adjacent liver
      parenchyma. Multi-detector computed tomography (MDCT) and magnetic resonance
      cholangiopancreatography (MRCP) are commonly used imaging modalities to assess
      the longitudinal and horizontal spread of tumor. 

PMID- 25969644
TI  - Tumefactive intramural gossypiboma of the urinary bladder mimicking an invasive
      adnexal malignancy.
AB  - A surgical swab retained in the body after surgery is known as 'Gossypiboma'. The
      purpose of this report is to highlight an intramural vesical gossypiboma
      mimicking an invasive adnexal malignancy. A 28-year-old multiparous, with open
      tubal ligation three years ago, presented with painless hematuria and a nontender
      mass on vaginal examination. USG suggested 'pelvic endometriosis' infiltrating
      into the bladder and cystoscopy showed no intraluminal extension of the mass.
      Contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI)
      misdiagnosed it as invasive malignancy of the fallopian tube. Exploratory
      laparotomy found it to be an intramural vesical gossypiboma. A pelvic gossypiboma
      infiltrating into the wall of the urinary bladder may easily be misinterpreted as
      an invasive pelvic malignancy on imaging and may make one consider unwarranted
      radical surgery. 

PMID- 25969645
TI  - Hepatic subcapsular flow: An early marker in diagnosing biliary atresia.
AB  - We report an interesting sign in the sonological evaluation of neonatal
      cholestasis, which is hepatic subcapsular flow. Hepatic subcapsular flow is an
      early and useful marker in diagnosing biliary atresia. 

PMID- 25969646
TI  - Concurrent nonfunctional paraganglioma of the retroperitoneum and urinary
      bladder: A case report with literature review.
AB  - Paragangliomas are the neuroendocrine tumors which arise from the chromaffin
      cell. Tumors arising from the adrenal medulla are known as pheochromocytomas,
      while others originating from the extra-adrenal site are known as extra-adrenal
      paragangliomas. Paraganglioma can be multifocal which can arise synchronously or
      metachronously. Paragangliomas are less functionally active than the
      pheochromocytomas; they secrete noradrenaline and rarely dopamine, while adrenal
      pheochromocytomas secrete adrenaline or nor-adrenaline. Nonfunctional multifocal
      paragangliomas are very rare. We report a case of a 45-year-old female with
      multifocal nonfunctional paragangliomas of the retroperitoneum and urinarybladder
      which were surgically removed, and the diagnosis was confirmed on histopathology.

PMID- 25969647
TI  - Real-time ultrasound: Key factor in identifying celiac artery compression
      syndrome.
AB  - The median arcuate ligament syndrome (MALS) or celiac artery compression syndrome
      (CACS) is a rare entity, presenting clinically with postprandial abdominal pain
      and weight loss. The diagnosis is made on computed tomography (CT) angiography,
      which reveals extrinsic compression of the proximal part of the celiac artery by
      the median arcuate ligament, producing a characteristic hooked appearance. We
      report a case of the celiac artery compression syndrome, diagnosed by Doppler USG
      evaluation. 

PMID- 25969648
TI  - Overseas exams - Perception of audience in a conference symposium: A survey.

PMID- 25969649
TI  - Do most radiologists in India really have a choice?

PMID- 25969650
TI  - Principles and practice of plagiarism: Perpetrators' perspective.

PMID- 25969651
TI  - Scientific concepts and applications of integrated discrete multiple organ co
      culture technology.
AB  - Over several decades, animals have been used as models to investigate the human
      specific drug toxicity, but the outcomes are not always reliably extrapolated to
      the humans in vivo. Appropriate in vitro human-based experimental system that
      includes in vivo parameters is required for the evaluation of multiple organ
      interaction, multiple organ/organ-specific toxicity, and metabolism of xenobiotic
      compounds to avoid the use of animals for toxicity testing. One such versatile in
      vitro technology in which human primary cells could be used is integrated
      discrete multiple organ co-culture (IdMOC). IdMOC system adopts wells-within-well
      concept that facilitates co-culture of cells from different organs in a discrete
      manner, separately in the respective media in the smaller inner wells which are
      then interconnected by an overlay of a universal medium in the large containing
      well. This novel in vitro approach mimics the in vivo situation to a great
      extent, and employs cells from multiple organs that are physically separated but
      interconnected by a medium that mimics the systemic circulation and provides for
      multiple organ interaction. Applications of IdMOC include assessment of multiple
      organ toxicity, drug distribution, organ-specific toxicity, screening of
      anticancer drugs, metabolic cytotoxicity, etc. 

PMID- 25969652
TI  - Efficacy of novel monoclonal antibody belimumab in the treatment of lupus
      nephritis.
AB  - Recently introduced into the market, belimumab (Benlysta) is a monoclonal
      antibody that has potential clinically efficacious applications for the treatment
      of lupus nephritis. Lupus nephritis is a major complication of systemic lupus
      erythematosus (SLE) that can lead to significant illness or even death without
      proper intervention and treatment. With vast implications through a novel
      mechanism, belimumab offers a new standard of treatment for physicians in the
      complications associated with SLE, specifically lupus nephritis. By targeting B
      cell signaling and maturation, belimumab is able to mitigate the underlying
      pathological complications surrounding SLE. Phase 3 clinical trials with
      belimumab have depicted clinically efficacious applications, suggesting belimumab
      as a revolutionary breakthrough in the treatment armamentarium for practicing
      clinicians. This article explains the precise mechanism of action of belimumab on
      the soluble protein BlyS that plays a major role in the pathogenesis of lupus
      nephritis. In addition, the extensive pharmacokinetics and clinical implications
      are exemplified in this review with belimumab's comparison with standard
      therapeutic guidelines for the treatment of lupus nephritis. 

PMID- 25969653
TI  - Identification of core active disaccharides in heparin for HGF-inducing activity.
AB  - OBJECTIVES: To ascertain the positions of sulfated groups for HGF-inducing
      activity using differently sulfated heparin disaccharides and to investigate
      whether the heparin disaccharide elevates HGF levels in plasma in vivo and exerts
      protective effects on acute liver injury. MATERIALS AND METHODS: The heparin
      disaccharides DeltaUA-GlcNS, DeltaUA (2S)-GlcN, DeltaUA-GlcNAc (6S), DeltaUA
      GlcNS (6S), DeltaUA (2S)-GlcNS, DeltaUA (2S)-GlcNAc (6S), DeltaUA-GlcNAc and
      DeltaUA (2S)-GlcNS (6S) were added to MRC-9 fibroblasts and HGF concentrations in
      culture media were determined by enzyme-linked immunosorbent assay. Furthermore,
      DeltaUA-GlcNS (100 MUg/head) was injected into C57BL/6 mice and plasma levels of
      HGF measured at 12 h. After acute hepatitis was induced by CCl4 (15 mg/kg) in
      mice, liver specimens were stained with hematoxylin and eosin (H and E). Levels
      of aspartate aminotransferase and alanine aminotransferase were measured at 24 h.
      RESULTS: Among the disaccharides investigated, DeltaUA-GlcNS, DeltaUA-GlcNAc (6S)
      and DeltaUA-GlcNS (6S) stimulated HGF production in MRC-9 fibroblasts. However,
      none of the 2-O-sulfated disaccharides [DeltaUA (2S)-GlcNS, DeltaUA (2S)-GlcNAc
      (6S) and DeltaUA (2S)-GlcNS (6S)] showed any activity despite the presence of N
      sulfated and/or 6-O-sulfated disaccharides. Thus, 2-O-sulfation of hexuronic acid
      has an inhibitory effect. Moreover, DeltaUA-GlcNS administration increased plasma
      levels of HGF in normal mice and prevented CCl4-induced liver injury in mice.
      CONCLUSIONS: N-sulfation and/or 6-O-sulfation of glucosamine with nonsulfated
      hexuronic acid provides a structural basis for the HGF-inducing activity of
      disaccharides. DeltaUA-GlcNS increases plasma levels of HGF and protects against
      CCl4-induced acute liver injury.

PMID- 25969654
TI  - Prescription errors in cancer chemotherapy: Omissions supersede potentially
      harmful errors.
AB  - OBJECTIVE: To estimate the frequency and type of prescription errors in patients
      receiving cancer chemotherapy. SETTINGS AND DESIGN: We conducted a cross
      sectional study at the day care unit of the Regional Cancer Centre (RCC) of a
      tertiary care hospital in South India. MATERIALS AND METHODS: All prescriptions
      written during July to September 2013 for patients attending the out-patient
      department of the RCC to be treated at the day care center were included in this
      study. The prescriptions were analyzed for omission of standard information,
      usage of brand names, abbreviations and legibility. The errors were further
      classified into potentially harmful ones and not harmful based on the likelihood
      of resulting in harm to the patient. Descriptive analysis was performed to
      estimate the frequency of prescription errors and expressed as total number of
      errors and percentage. RESULTS: A total of 4253 prescribing errors were found in
      1500 prescriptions (283.5%), of which 47.1% were due to omissions like name, age
      and diagnosis and 22.5% were due to usage of brand names. Abbreviations of pre
      medications and anticancer drugs accounted for 29.2% of the errors. Potentially
      harmful errors that were likely to result in serious consequences to the patient
      were estimated to be 11.7%. CONCLUSIONS: Most of the errors intercepted in our
      study are due to a high patient load and inattention of the prescribers to
      omissions in prescription. Redesigning prescription forms and sensitizing
      prescribers to the importance of writing prescriptions without errors may help in
      reducing errors to a large extent.

PMID- 25969655
TI  - Parents' awareness and perspective on off-label medicines use in children.

PMID- 25969656
TI  - Comparison of agreement and rational uses of the WHO and Naranjo adverse event
      causality assessment tools.

PMID- 25969657
TI  - Violation of publication ethics in manuscripts: Analysis and perspectives.

PMID- 25969658
TI  - Hypokalemia and rhabdomyolysis.
AB  - The adverse drug event manager of the Capital Region of Denmark received a report
      of a 65-year-old male with type II diabetes and long-lasting treatment with
      indapamide. In addition, he had a history of a high consumption of licorice. For
      2 weeks, the patient suffered from myalgia, which the general practitioner
      suspected to be polymyalgia rheumatica and referred him to the hospital. Initial
      blood samples revealed a reduced potassium concentration of 1.5 mmol/L (reference
      value: 6.6-4.6 mmol/L) and an elevated creatine kinase of 18,400 IU/L (reference
      value: 40-280 IU/L). We believe that the patient developed rhabdomyolysis due to
      severe hypokalemia, possibly induced by a pharmacodynamic interaction between
      licorice and indapamide. 

PMID- 25969659
TI  - Intravenous ranitidine: Rapid bolus can lead to cardiac arrest.
AB  - This is a rare case report of a 30-year-old male, who was admitted to the
      Maxillofacial Surgery Department of the Dental College for a malunited fracture
      of the mandible and zygomatic bones. He was given oral medications namely,
      cefixime, metronidazole, ondansetron, and ranitidine for three days prior to the
      operation with complete normal preoperative workup. He had no significant past
      medical or family history. On the day of the operation, he was given injectable
      dexamethasone, cefotaxime, ondansetron, ranitidine, and metronidazole half-an
      hour prior to the operation. In less than five minutes of giving a bolus
      ranitidine injection, the patient developed a cardiac arrest and was resuscitated
      by the anesthetist team on duty. He was transferred to the Intensive Care Unit
      (ICU) on a ventilator, which was soon removed and the patient was off
      vasopressors, with stable vitals for 24 hours after the event. He was then
      transferred to the general ward of Medicine Department and observed for a further
      two days during which the patient remained uneventful and was finally transferred
      back to the Dental Department. 

PMID- 25969660
TI  - Dexamethasone-induced withdrawal seizure.
AB  - Dexamethasone-induced withdrawal seizure, which is a very rare and uncommon
      event, occurred after discontinuation of steroid therapy that was taken to
      increase weight by the patient. The pathogenesis is not well understood. In this
      submission, we have highlighted the fact that withdrawal of steroid has a
      propensity to cause seizure as a rare withdrawal phenomenon. 

PMID- 25969661
TI  - Hypersensitivity reaction with deferasirox.
AB  - Thalassemias comprise a group of hereditary blood disorders. Thalassemia major
      presents with anemia within the first 2 years of life requiring frequent blood
      transfusions for sustaining life. Regular blood transfusions lead to iron
      overload-related complications. Prognosis of thalassemia has improved because of
      the availability of iron-chelating agents. Oral iron chelators are the mainstay
      of chelation therapy. Deferasirox is a new-generation oral iron chelator for once
      daily usage. We herein describe a patient of beta thalassemia major who developed
      an allergic manifestation in the form of erythematous pruritic skin rashes to the
      oral iron chelator deferasirox. This is a rare adverse reaction reported with
      deferasirox that led to a therapeutic dilemma in this particular case. 

PMID- 25969662
TI  - Telmisartan aggravates pustular psoriasis.
AB  - Pustular psoriasis is characterized by abrupt onset of macroscopic pustules
      associated with erythema and symptoms of burning pain and constitutional
      symptoms. There are several precipitating factors, both physiological such as
      pregnancy and routinely prescribed drugs like antihypertensives, antifungals,
      corticosteroids and progesterone. We present a case of a 50-year-old male patient
      with pustular psoriasis, well controlled on oral methotrexate, who presented with
      sudden exacerbation of pustular psoriasis following the use of telmisartan. This
      case is presented due to the absence of prior reports of telmisartan aggravating
      pustular psoriasis. 

PMID- 25969663
TI  - Adrenal suppression following herbal remedy for rheumatoid arthritis.
AB  - A patient suffering from rheumatoid arthritis who had extreme adrenal suppression
      as a result of chronic use of herbal medicines presented with complications of
      adrenal suppression such as muscle weakness. He also had psychiatric disturbances
      such as confusion and suicidal tendency. Steroids in the herbal medication were
      found and hence there exists a need for investigation into their safety and
      efficacy. 

PMID- 25969664
TI  - Olanzapine-induced tender pitting pre-tibial edema.
AB  - Antipsychotic-induced edema is uncommonly encountered in clinical practice. We
      report a case of tender pitting pre-tibial edema with olanzapine in a woman with
      no medical comorbidities. The peculiar distribution of edema resulted in
      diagnostic confusion necessitating specific investigations. Eventually, the edema
      resolved following complete stoppage of the drug, but caused distress to the
      patient and the caregiver. 

PMID- 25969665
TI  - VACCRaksha Calc: A computer program for the calculation of vaccine potency.

PMID- 25969666
TI  - Suvorexant: The first orexin receptor antagonist to treat insomnia.
AB  - Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors
      and a few other classes of drugs used for different co-morbidities. A novel
      approach to treat insomnia has been introduced recently, with the approval of
      suvorexant, the first in a new class of orexin receptor antagonists. Orexin
      receptors in the brain have been found to play an important role in the
      regulation of various aspects of arousal and motivation. The drugs commonly used
      for insomnia therapy to date, have often been associated with adverse effects,
      such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart
      from the risk of dependence on chronic use. Suvorexant has not shown these
      adverse effects because of its unique mechanism of action. It also appears to be
      suitable as a chronic therapy for insomnia, because of minimal physical
      dependence. The availability of this new drug as an effective and safe
      alternative is an important and welcome development in insomnia management. 

PMID- 25969667
TI  - Erratum: Adverse drug reactions of imatinib in patients with chronic myeloid
      leukemia: A single-center surveillance study: Erratum.
AB  - [This corrects the article on p. 30 in vol. 6, PMID: 25709349.]. 

PMID- 25969668
TI  - MiR-124 suppresses cell motility and adhesion by targeting talin 1 in prostate
      cancer cells.
AB  - BACKGROUND: MicroRNA is a type of endogenous non-coding RNA implicated in various
      cellular processes, and has been intensely investigated in the field of cancer
      research for many years. Here, we investigated the functions and mechanisms of
      miR-124 in prostate cancer, which is a putative tumor suppressor reported in many
      carcinomas. METHODS: Using bioinformatics, talin 1 was indicated as a potential
      target of miR-124. We examined the expression levels of miR-124 and talin 1 in
      tissue specimens and cell lines. To explore the relationship between miR-124 and
      talin 1, miR-124 mimics, miR-124 inhibitors, and talin 1 small interfering RNA
      (siRNA) were transiently transfected into cancer cell lines, followed by analysis
      using luciferase reporter assays. Next, to investigate the functions of miR-124
      in prostate cancer, we performed cell attachment, migration, and invasion assays.
      A rescue experiment was also conducted to demonstrate whether miR-124 suppressed
      cell adhesion and motility by targeting talin 1. Finally, we examined the related
      signaling pathways of miR-124 and talin 1. RESULTS: MiR-124 was down-regulated in
      prostate cancer specimens and cell lines, while talin 1 was over-expressed in
      prostate cancer specimens and cell lines. These results showed an inverse
      correlation of miR-124 and talin 1 expression. Similar to talin 1 siRNA,
      overexpression of miR-124 by transient transfection of mimics led to a
      significant decrease in talin 1 levels. Luciferase report assays showed that the
      seed sequence of the talin 1 3'-untranslated region was a target of miR-124.
      Functional investigations revealed anti-attachment, anti-migration, and invasion
      promoting effects of miR-124 in prostate cancer cells. The rescue experiment
      confirmed that miR-124 exerted its biological functions by targeting talin 1.
      Finally, we found that miR-124 and talin 1 impaired cellular adhesion and
      motility through integrins and the focal adhesion kinase/Akt pathway.
      CONCLUSIONS: Our study demonstrated biological roles and the related mechanism of
      miR-124 in prostate cancer. The results indicate that talin 1 is very likely a
      novel player in the anti-metastatic signaling network of miR-124. By down
      regulation of talin 1, miR-124 impairs the adhesion, migration, and invasion of
      prostate cancer cells.

PMID- 25969669
TI  - Reduced expression of peroxisome proliferator-activated receptor alpha in BAL and
      blood T cells of non-lofgren's sarcoidosis patients.
AB  - BACKGROUND: Sarcoidosis is a granulomatous disease affecting in particular the
      lungs. The peroxisome proliferator-activated receptors (PPARs) play important
      regulatory roles in inflammation. The aim of this study was to gain more insight
      about the expression of all three PPARs (alpha, beta/delta and gamma) in
      sarcoidosis. METHODS: Bronchoalveolar lavage (BAL) cells and peripheral blood
      cells were obtained from healthy controls (HC) and sarcoidosis patients with
      Lofgren's syndrome (LS) and without Lofgren's syndrome (non-LS). PPARs mRNA
      expression was analyzed in total BAL cells and in FACS (Fluorescence-activated
      cell sorting) sorted alveolar macrophages (AM) and CD4(+) T cells respectively by
      comparative RT-PCR. PPARs protein expression was analyzed in AM, and in BAL and
      blood CD4(+) and CD8(+) T cells by flow cytometry. RESULTS: In BAL CD4(+) T
      cells, we noticed a significantly lower PPARalpha mRNA expression in sarcoidosis
      patients compared with HC. In non-LS patients, a significantly lower PPARalpha
      protein expression in BAL CD4(+) T cells was detected as compared with LS
      patients. In peripheral blood CD4(+) T cells, non-LS patients had a significantly
      lower expression of PPARalpha and PPARgamma compared with LS patients.
      CONCLUSION: The lower protein expression of PPARalpha and PPARgamma could
      contribute to the persistent T-cell driven inflammation noted especially in non
      resolving sarcoidosis, common in non-LS patients.

PMID- 25969670
TI  - Proteomic study of different culture medium serum volume fractions on RANKL
      dependent RAW264.7 cells differentiating into osteoclasts.
AB  - BACKGROUND: Cultivation of osteoclasts is a basic tool for investigating
      osteolytic bone diseases. Fetal bovine serum (FBS) is the standard supplement
      used for in vitro cell culture medium. Typically, the serum volume fraction used
      for osteoclast cultivation is 10%. In this study, we investigated the use of a
      low serum (1% FBS) model for culturing osteoclasts. RESULTS: To confirm the
      validity of this model for use in osteoclast research, we compared the capacity
      for osteoclastogenesis and bone resorption of RANKL-induced RAW 264.7 cells
      cultured in medium supplemented with 10% FBS and 1% FBS. Osteoclasts were
      successfully generated in medium supplemented with 1% FBS, and exhibited
      prolonged longevity and similar bone resorbing ability to those generated in
      medium supplemented with 10% FBS, although the osteoclasts were smaller in size.
      Proteomics and bioinformatics analyses were performed to assess the suitability
      of osteoclasts formed in low serum-containing medium for use in research focusing
      on osteoclast differentiation and function. Our study demonstrated that a total
      of 100 proteins were differentially expressed in cells cultured in medium
      containing 1% FBS, of which 29 proteins were upregulated, and 71 proteins were
      downregulated. Bioinformatics analysis showed that the electron transport chain
      and oxidative phosphorylation pathways were downregulated obviously; however, the
      osteoclast signaling pathway was unaffected. The data have been deposited to the
      ProteomeXchange with identifier PXD001935. CONCLUSION: Our study provides clear
      evidence of the validity of the low serum model for use in studying RANKL
      dependent osteoclasts differentiation and bone resorption with the advantage of
      prolonged survival time.

PMID- 25969671
TI  - Autoinflammatory diseases: a possible cause of thrombosis?
AB  - Autoinflammatory diseases are a group of disorders due to acquired or hereditary
      disfunction of innate immune system and characterized by systemic or localized
      manifestations. The prototype is Familial Mediterranean Fever, a monogenic
      hereditary disorder, whose causing gene (MeFV gene) was identified in 1997 and
      opened the way to a new fascinanting chapter of rheumatology. A growing body of
      monogenic and poligenic autoinflammatory disorders has been described since then.
      Arterial and venous thrombosis is a common medical problem, with significant
      morbidity and mortality. Strong evidences from basic research and clinical
      epidemiological studies support the theory that inflammation and thrombosis can
      be associated. Because of their recurrent/chronic inflammatory nature,
      autoinflammatory diseases are a putative cause of thrombotic manifestations. In
      the present work, we reviewed the available evidences about monogenic
      autoinflammatory disorders, complicated by thrombotic manifestations. 

PMID- 25969672
TI  - Options for the Medical Treatment of Peyronie's Disease.

PMID- 25969673
TI  - Relations among early object recognition skills: Objects and letters.
AB  - Human visual object recognition is multifaceted, with several domains of
      expertise. Developmental relations between young children's letter recognition
      and their 3-dimensional object recognition abilities are implicated on several
      grounds but have received little research attention. Here, we ask how
      preschoolers' success in recognizing letters relates to their ability to
      recognize 3-dimensional objects from sparse shape information alone. A relation
      is predicted because perception of the spatial relations is critical in both
      domains. Seventy-three 2 1/2- to 4-year-old children completed a Letter
      Recognition task, measuring the ability to identify a named letter among 3
      letters with similar shapes, and a "Shape Caricature Recognition" task, measuring
      recognition of familiar objects from sparse, abstract information about their
      part shapes and the spatial relations among those parts. Children also completed
      a control "Shape Bias" task, in which success depends on recognition of overall
      object shape but not of relational structure. Children's success in letter
      recognition was positively related to their shape caricature recognition scores,
      but not to their shape bias scores. The results suggest that letter recognition
      builds upon developing skills in attending to and representing the relational
      structure of object shape, and that these skills are common to both 2-dimensional
      and 3-dimensional object perception.

PMID- 25969674
TI  - Diffuse Liver Metastasis of Small-Cell Lung Cancer Presenting as Acute Liver
      Failure and Diagnosed by Transjugular Liver Biopsy: A Rare Case in Whom Nodular
      Lesions Were Detected by Enhanced CT Examination.
AB  - Small-cell lung cancer (SCLC) is a subgroup of lung cancer with a high frequency
      of liver metastasis, which is a predictor of poor prognosis. Diffuse liver
      metastases of SCLC with no visible nodular lesions in the liver when examined
      using computed tomography (CT) are relatively rare; however, a few cases with
      rapid progression to acute liver failure that were diagnosed after death have
      been reported. In this paper, we report a 63-year-old man with diffuse liver
      metastases of SCLC that were histologically diagnosed using a transjugular liver
      biopsy while the patient was alive, even though no lesions were visible during a
      contrast-enhanced CT examination. 

PMID- 25969675
TI  - Inflammatory polyp in the common bile duct with pancreaticobiliary maljunction.
AB  - A 63-year-old woman was admitted because of epigastric pain and obstructive
      jaundice. Endoscopic retrograde cholangiopancreatography and intraductal
      ultrasonography revealed a 25-mm papillary nodule in the middle to inferior
      portion of the common bile duct (CBD). Pancreaticobiliary maljunction (PBM) was
      also identified. Contrast-enhanced computed tomography also showed an enhanced
      nodule in the CBD, and we suspected intraductal papillary neoplasm of the bile
      duct. We performed pylorus-preserving pancreatoduodenectomy. Postoperative
      pathological examination revealed an inflammatory polyp in the middle CBD.
      Inflammatory polyp in the bile duct is rare and there are no previous reports
      accompanied by PBM. PBM is a major risk factor for biliary tract cancer.
      Preoperative diagnosis of a benign disorder was difficult in this case. 

PMID- 25969676
TI  - Alcohol abuse and alcoholic liver cirrhosis leading to spontaneous muscle
      hematoma: an event fraught with danger.
AB  - Alcohol abuse is associated with both potentiating and antagonizing hemostatic
      states. Liver cirrhosis is an independent causal factor for many bleeding
      complications. The long-term effects of alcohol abuse coupled with advanced liver
      cirrhosis are additive in favor of bleeding. We report the case of a patient with
      a history of alcohol abuse who presented with liver cirrhosis and nontraumatic
      muscle hematoma diagnosed as a spontaneous hematoma of the gastrocnemius muscle.
      He was managed conservatively with infusions of fresh frozen plasma and
      platelets, which resulted in resolution of the hematoma. The pathogenesis of
      'spontaneous' muscle hematoma remains anecdotal, but since it is reported in
      patients on anticoagulant therapy or with hemostatic disorders, it is
      hypothetically related to severely deranged coagulation. Here we review the
      relevant literature pertaining to the pathogenesis, presentation and treatment
      options available for treating this often fatal complication of bleeding
      diatheses. 

PMID- 25969677
TI  - Ustekinumab as an alternative treatment option for chronic pityriasis rubra
      pilaris.
AB  - Pityriasis rubra pilaris (PRP) is an exceptionally rare, chronic inflammatory
      dermatosis of unknown etiology. Patients classically present with small,
      follicular keratosis and salmon-colored plaques that begin at the head and neck
      and slowly progress to widespread erythroderma including the palms and soles. It
      is difficult to distinguish PRP from other inflammatory dermatoses; however,
      features that help aid in the diagnosis include 'islands' of spared skin,
      orangish hue and typical findings on biopsy. There are no specific guidelines on
      therapy and treatment options include corticosteroids, vitamin D analogs,
      retinoids, methotrexate, cyclosporine, azathioprine and tumor necrosis factor
      alpha antagonists. Unfortunately options are limited for patients when these
      drugs do not work. We report a case of chronic PRP, refractory to conventional
      treatment, successfully treated with ustekinumab monotherapy. The patient was
      treated with 90 mg subcutaneous ustekinumab injections and began to show
      improvement within only 8 weeks. Long-term control of the disease has been
      attained without any significant side effects. We report this case to show that
      ustekinumab can be used as an alternative treatment method for patients with
      chronic, unremitting PRP. Treatment response is remarkably rapid and the
      infrequent dosing leads to patient compliance and a significantly improved
      quality of life. 

PMID- 25969678
TI  - Dyschromatosis universalis hereditaria with renal failure.
AB  - Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant
      inherited dermatosis which usually appears during childhood and is characterized
      by dyspigmentation, with both hypopigmented and hyperpigmented macules. We report
      a case of DUH with unexplained childhood-onset renal failure. The association
      between DUH and renal failure is yet to be proven by further studies. 

PMID- 25969679
TI  - Cheek and periorbital peculiar discoid lupus erythematosus: rare clinical
      presentation mimicking tinea faciei, cutaneous granulomatous disease or
      blepharitis.
AB  - We present clinically peculiar facial discoid lupus erythematosus (DLE) that
      mimicked tinea faciei. Although DLE is a chronic autoimmune dermatosis, it has a
      variety of rare clinical presentations, including periorbital DLE, comedonic DLE
      and hypertrophic DLE recently. In this case, a scaly, erythematous lesion on the
      eyelid and the central healed, mildly elevated, annularly distributed facial DLE
      mimicked tinea faciei, complicating our diagnosis. 

PMID- 25969680
TI  - Lung cancer presenting as a soft-tissue metastasis.
AB  - Soft-tissue metastasis refers to the growth of cancer cells, originating from
      internal cancer, in soft tissues. In most cases, soft-tissue metastases develop
      after initial diagnosis of the primary internal malignancy and late in the course
      of the disease. In very rare cases, they may occur at the same time or before the
      primary cancer has been detected. In our cases, the soft-tissue metastases and
      the primary lung cancer were diagnosed at the same time. 

PMID- 25969681
TI  - Long-term disease control by pomalidomide-/dexamethasone-based therapy in a
      patient with advanced multiple myeloma: a case report and review of the
      literature.
AB  - BACKGROUND: Therapy for multiple myeloma (MM) has substantially improved in the
      era of immunomodulatory drugs and bortezomib. However, the prognosis of patients
      with progressive disease despite treatment with these 'novel agents' remains
      poor. Recently, pomalidomide was approved in this setting, but a median
      progression-free survival of <4 months still leaves room for improvement.
      Pomalidomide-based combination therapies are currently under investigation, but
      data on long-term treatment are lacking. CASE REPORT: We present the case of a 68
      year-old woman with refractory MM who received pomalidomide in combination with
      various drugs including anthracyclines, alkylators and proteasome inhibitors.
      Initially, major hematological toxicities and infectious complications including
      a hepatitis B virus reactivation were encountered. With careful dose adjustments
      and selection of combination partners, pomalidomide treatment was maintained for
      over 4 years and led to a sustained partial remission. In particular, the well
      tolerated regimen of bortezomib, cyclophosphamide and dexamethasone together with
      pomalidomide was administered for >30 cycles. CONCLUSION: This case illustrates
      the value of an individualized approach to myeloma care given an increasing
      availability of 'novel agents'. Tailored treatment using these drugs as a
      backbone is essential to achieve long-lasting responses and minimize side
      effects.

PMID- 25969682
TI  - Spontaneous intracranial hypotension manifesting as a unilateral subdural
      hematoma with a marked midline shift.
AB  - Spontaneous intracranial hypotension (SIH) is a syndrome in which hypovolemia of
      the cerebrospinal fluid (CSF) results in various symptoms. Although its prognosis
      is usually benign, cases with a rapid neurologic deterioration resulting in an
      altered mental status have been reported. One of the characteristic radiographic
      findings in such cases is the presence of bilateral accumulation of subdural
      fluid (hematoma/hygroma). When SIH-related subdural hematoma is present only
      unilaterally with a concomitant midline shift, making an accurate diagnosis may
      be challenging, and inadvertent hematoma evacuation may result in further
      neurologic deterioration. We report a 58-year-old woman with an altered mental
      status who had visited a local hospital and in whom a brain CT showed a
      unilateral subdural hematoma with a marked midline shift. She was referred to our
      department because of her neurologic deterioration after hematoma evacuation. A
      CT myelography revealed a massive CSF leakage in the entire thoracic epidural
      space. She made a full neurologic recovery following blood patch therapy. Our
      case is unique and educational because the suspicion for SIH as an underlying
      cause of subdural hematoma is warranted in nongeriatric patients not only with
      bilateral but also unilateral lesions. An immediate search for CSF leakage may be
      important in cases with failed hematoma evacuation surgery. 

PMID- 25969683
TI  - Seronegative Neuromyelitis Optica Spectrum Disorder following Exposure to
      Hepatitis B Vaccination.
AB  - Controversy exists regarding a potential link between exposure to recombinant
      hepatitis B vaccine (HBV) and central nervous system demyelinating diseases.
      Here, we present a case of seronegative neuromyelitis optica spectrum disorder
      (NMOSD) following exposure to HBV. A 28-year-old man developed painful eye
      movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss,
      ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9.
      Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided
      internal capsule lesion. Cerebrospinal fluid analysis was normal, including
      negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative.
      The patient's visual symptoms improved after treatment with steroids and plasma
      exchange. He received plasma exchange weekly for 4 weeks with decreased numbness
      and tingling as well as improved coordination. Treatment with mycophenolate
      mofetil was started, and the patient remains clinically stable with near
      resolution of his prior symptoms. Neuromyelitis optica is characterized by optic
      neuritis and/or longitudinally extensive transverse myelitis. While our patient
      tested seronegative for AQP4-IgG (which remains negative in 10-50% of NMOSD
      cases, despite testing with the most sensitive assays available), he did meet
      NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD
      onset or relapse associated with exposure to various vaccines, but to our
      knowledge this represents the first published report of NMOSD onset following
      exposure to HBV. While causality between vaccination and CNS demyelinating
      disease remains elusive, it is important to report these cases to help develop
      safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD. 

PMID- 25969685
TI  - Conjunctival Attachment of a Live Paralysis Tick, Ixodes holocyclus, in a Child:
      A Case Report.
AB  - We describe a rare clinical finding of conjunctival tick attachment in a child. A
      10-year-old boy presented to the clinic with right-eye itch. He was found to have
      a live tick firmly attached to his right temporal conjunctiva. The tick was
      identified as the larval stage of the paralysis tick, Ixodes holocyclus. The tick
      was removed completely by conjunctival excision. Although various methods of
      removing a tick have been described in the literature, the goal of treatment is
      the safe and complete removal of the tick to prevent further transmission of
      pathogens, allergens, and toxins to the patient. 

PMID- 25969684
TI  - Familial hemiplegic migraine type 1 associated with parkinsonism: a case report.
AB  - Familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and
      spinocerebellar ataxia type 6 (SCA6) are allelic disorders caused by mutations in
      the CACNA1A gene on chromosome 19p13. It is well described that FHM1 can present
      with cerebellar signs, but parkinsonism has not previously been reported in FHM1
      or EA2 even though parkinsonism has been described in SCA6. We report a 63-year
      old woman with FHM1 caused by an R583Q mutation in the CACNA1A gene, clinically
      presenting with migraine and permanent cerebellar ataxia. Since the age of 60
      years, the patient also developed parkinsonism with rigidity, bradykinesia and a
      resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of
      substance in the basal ganglia, which is in contrast to the typically normal MRI
      in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single
      photon emission computed tomography demonstrated a decreased DAT-binding
      potential in the putamen. We wish to draw attention to FHM1 associated with
      parkinsonism; however, whether the reported case is a consequence of FHM1 being
      allelic to SCA6, unknown modifiers to the specific R583Q CACNA1A mutation or
      idiopathic Parkinson's disease remains unanswered. 

PMID- 25969686
TI  - Retinal angiomatous proliferation in an eye with cuticular drusen.
AB  - PURPOSE: To report the presence of retinal angiomatous proliferation (RAP) in an
      eye with cuticular drusen detected by fluorescein and indocyanine green
      angiography by confocal scanning laser ophthalmoscopy and by spectral-domain
      optical coherence tomography (SD-OCT). METHODS: Case report of a 65-year-old
      Japanese woman with cuticular drusen. RESULTS: At her first ophthalmic
      examination, her visual acuity was 20/20 in both eyes. An ophthalmoscopy showed
      many small subretinal pigment epithelial deposits in both eyes. These deposits
      had a 'saw-tooth pattern' in the SD-OCT images. During the follow-up examination,
      retinal hemorrhages were observed, and fluorescein angiography showed a 'stars-in
      the-sky' appearance and intraretinal neovascularization. The patient was
      diagnosed with cuticular drusen associated with RAP. CONCLUSION: We suggest that
      the cuticular drusen were associated with RAP, so periodic follow-up examinations
      are needed for patients with cuticular drusen for the early detection and
      treatment of RAP.

PMID- 25969687
TI  - The effect of ptosis on cataract surgical planning.
AB  - PURPOSE: To describe a patient complaining of 'ghosting' and 'shadowing' after
      bilateral, sequential cataract extraction with toric intraocular lens (IOL)
      implantation who was found to have significant eyelid ptosis. METHODS: The
      following is a case report. RESULTS: The patient's complaints arose a few weeks
      after surgery. By the second postoperative month, the patient's keratometry had
      changed compared to preoperative measurements. Because of significant ptosis, the
      patient underwent upper eyelid surgery. Four months later, he was found to have
      less corneal astigmatism than had been measured prior to cataract surgery.
      Following 2 stable examinations, a Prevue lens based on Hartmann-Shack wavefront
      aberrometry was made for each eye, which the patient said significantly improved
      his quality of vision. Wavefront-guided photorefractive keratectomy (PRK) was
      performed 6 months after cataract surgery. One year after PRK, the patient's
      symptoms had disappeared, his uncorrected visual acuity was 20/20 in the right
      eye and 20/15 in the left, and he was satisfied with his quality of vision.
      CONCLUSIONS: Bilateral toric IOLs were implanted in this patient based on
      measurements of corneal astigmatism that changed after cataract surgery and
      changed further after ptosis repair. This case demonstrates the importance of
      evaluating eyelid position in cataract surgical planning as ptosis can contribute
      significantly to corneal astigmatism. Patient education is important in the
      setting of higher expectations from purchase of premium lens implants.

PMID- 25969688
TI  - Fertility and Symptom Relief following Robot-Assisted Laparoscopic Myomectomy.
AB  - Objective. To examine success of robot-assisted laparoscopic myomectomy (RALM)
      measured by sustained symptom relief and fertility. Methods. This is a
      retrospective survey of 426 women who underwent RALM for fibroids, symptom
      relief, or infertility at three practice sites across the US. We examined rates
      of symptom recurrence and pregnancy and factors associated with these outcomes.
      Results. Overall, 70% of women reported being symptom-free, with 62.9% free of
      symptoms after three years. At >3 years, 66.7% of women who underwent surgery to
      treat infertility and 80% who were also symptom-free reported achieving
      pregnancy. Factors independently associated with symptom recurrence included
      greater time after surgery, preoperative dyspareunia, multiple fibroid surgeries,
      smoking after surgery, and preexisting diabetes. Factors positively correlated
      with achieving pregnancy included desiring pregnancy, prior pregnancy, greater
      time since surgery, and Caucasian race. Factors negatively correlated with
      pregnancy were advanced age and symptom recurrence. Conclusions. This paper, the
      first to examine symptom recurrence after RALM, demonstrates both short- and long
      term effectiveness in providing symptom relief. Furthermore, RALM may have the
      potential to improve the chance of conception, even in a population at high risk
      of subfertility, with greater benefits among those who remain symptom-free. These
      findings require prospective validation. 

PMID- 25969689
TI  - The Combined Extract of Zingiber officinale and Zea mays (Purple Color) Improves
      Neuropathy, Oxidative Stress, and Axon Density in Streptozotocin Induced Diabetic
      Rats.
AB  - Based on the protective effect of the combined extract of purple waxy corn and
      ginger (PWCG) on oxidative stress related disorders in diabetic condition, we
      aimed to determine the effect of PWCG on the functional, biochemical, and
      structural change of the lesion nerve in streptozotocin- (STZ-) diabetic rats.
      PWCG at doses of 100, 200, and 300 mg.kg(-1) BW were orally given to STZ-diabetic
      rats which were subjected to chronic constriction (CCI) at right sciatic nerve
      for 21 days. The blood sugar was assessed before and at the end of study whereas
      the sciatic function index (SFI), paw withdrawal threshold intensity (PWTI), and
      paw withdrawal latency (PWL) were assessed every 3 days until the end of study.
      At the end of study, the determination of nerve conduction velocity (NCV), axon
      density, oxidative stress status, and aldose reductase (AR) activity of the
      lesion nerve were performed. It was found that PWCG improved SFI, PWTI, PWL, and
      NCV together with the improved oxidative stress status and the axon density in
      the lesion nerve. No changes of AR activity or blood sugar level were observed.
      Therefore, PWCG might improve the functional and structural changes in STZ
      diabetic rats plus CCI via the improved oxidative stress status. 

PMID- 25969690
TI  - Network-based inference methods for drug repositioning.
AB  - Mining potential drug-disease associations can speed up drug repositioning for
      pharmaceutical companies. Previous computational strategies focused on prior
      biological information for association inference. However, such information may
      not be comprehensively available and may contain errors. Different from previous
      research, two inference methods, ProbS and HeatS, were introduced in this paper
      to predict direct drug-disease associations based only on the basic network
      topology measure. Bipartite network topology was used to prioritize the
      potentially indicated diseases for a drug. Experimental results showed that both
      methods can receive reliable prediction performance and achieve AUC values of
      0.9192 and 0.9079, respectively. Case studies on real drugs indicated that some
      of the strongly predicted associations were confirmed by results in the
      Comparative Toxicogenomics Database (CTD). Finally, a comprehensive prediction of
      drug-disease associations enables us to suggest many new drug indications for
      further studies. 

PMID- 25969691
TI  - A novel method for identifying disease associated protein complexes based on
      functional similarity protein complex networks.
AB  - BACKGROUND: Protein complexes formed by non-covalent interaction among proteins
      play important roles in cellular functions. Computational and purification
      methods have been used to identify many protein complexes and their cellular
      functions. However, their roles in terms of causing disease have not been well
      discovered yet. There exist only a few studies for the identification of disease
      associated protein complexes. However, they mostly utilize complicated
      heterogeneous networks which are constructed based on an out-of-date database of
      phenotype similarity network collected from literature. In addition, they only
      apply for diseases for which tissue-specific data exist. METHODS: In this study,
      we propose a method to identify novel disease-protein complex associations.
      First, we introduce a framework to construct functional similarity protein
      complex networks where two protein complexes are functionally connected by either
      shared protein elements, shared annotating GO terms or based on protein
      interactions between elements in each protein complex. Second, we propose a
      simple but effective neighborhood-based algorithm, which yields a local
      similarity measure, to rank disease candidate protein complexes. RESULTS:
      Comparing the predictive performance of our proposed algorithm with that of two
      state-of-the-art network propagation algorithms including one we used in our
      previous study, we found that it performed statistically significantly better
      than that of these two algorithms for all the constructed functional similarity
      protein complex networks. In addition, it ran about 32 times faster than these
      two algorithms. Moreover, our proposed method always achieved high performance in
      terms of AUC values irrespective of the ways to construct the functional
      similarity protein complex networks and the used algorithms. The performance of
      our method was also higher than that reported in some existing methods which were
      based on complicated heterogeneous networks. Finally, we also tested our method
      with prostate cancer and selected the top 100 highly ranked candidate protein
      complexes. Interestingly, 69 of them were evidenced since at least one of their
      protein elements are known to be associated with prostate cancer. CONCLUSIONS:
      Our proposed method, including the framework to construct functional similarity
      protein complex networks and the neighborhood-based algorithm on these networks,
      could be used for identification of novel disease-protein complex associations.

PMID- 25969692
TI  - Algorithms for detecting and analysing autocatalytic sets.
AB  - BACKGROUND: Autocatalytic sets are considered to be fundamental to the origin of
      life. Prior theoretical and computational work on the existence and properties of
      these sets has relied on a fast algorithm for detectingself-sustaining
      autocatalytic sets in chemical reaction systems. Here, we introduce and apply a
      modified version and several extensions of the basic algorithm: (i) a
      modification aimed at reducing the number of calls to the computationally most
      expensive part of the algorithm, (ii) the application of a previously introduced
      extension of the basic algorithm to sample the smallest possible autocatalytic
      sets within a reaction network, and the application of a statistical test which
      provides a probable lower bound on the number of such smallest sets, (iii) the
      introduction and application of another extension of the basic algorithm to
      detect autocatalytic sets in a reaction system where molecules can also inhibit
      (as well as catalyse) reactions, (iv) a further, more abstract, extension of the
      theory behind searching for autocatalytic sets. RESULTS: (i) The modified
      algorithm outperforms the original one in the number of calls to the
      computationally most expensive procedure, which, in some cases also leads to a
      significant improvement in overall running time, (ii) our statistical test
      provides strong support for the existence of very large numbers (even millions)
      of minimal autocatalytic sets in a well-studied polymer model, where these
      minimal sets share about half of their reactions on average, (iii) "uninhibited"
      autocatalytic sets can be found in reaction systems that allow inhibition, but
      their number and sizes depend on the level of inhibition relative to the level of
      catalysis. CONCLUSIONS: (i) Improvements in the overall running time when
      searching for autocatalytic sets can potentially be obtained by using a modified
      version of the algorithm, (ii) the existence of large numbers of minimal
      autocatalytic sets can have important consequences for the possible evolvability
      of autocatalytic sets, (iii) inhibition can be efficiently dealt with as long as
      the total number of inhibitors is small.

PMID- 25969693
TI  - HPV prevalence and risk of pre-cancer and cancer in regular immigrants in Italy:
      results from HPV DNA test-based screening pilot programs.
AB  - ?: Immigrants from low- and medium-income countries have a higher risk of
      cervical cancer due both to barriers in access to screening and to higher human
      papillomavirus (HPV) prevalence. In the near future many screening programmes in
      industrialised countries will replace Pap test with HPV as primary test. In order
      to plan future interventions, it is essential to understand how the HPV screening
      performs in immigrant women. METHODS: We conducted a survey on the main
      performance indicators from some of the HPV DNA-based pilot programmes in Italy,
      comparing regular immigrant women, identified as women resident in Italy who were
      born abroad, with women who were born in Italy. All the programmes applied the
      same protocol, with HPV as stand-alone test starting for women of 25 or 35 to 64
      years of age. Cytology triage is performed for positive women; those ASC-US or
      more severe are referred directly to colposcopy; negative women are referred to
      repeat HPV after one year. RESULTS: Overall, 162,829 women were invited, of whom
      22,814 were born abroad. Participation was higher for Italy-born than born abroad
      (52.2% vs. 43.6%), particularly for women over 45 years. HPV positivity rate was
      higher in immigrants: 7.8% vs. 6.1%, age-adjusted Relative Risk (age-adj RR)
      1.18, 95% confidence interval (95% CI) 1.13-1.22. The proportion of women with
      positive cytology triage was similar in the two groups (42%). Cervical
      Intraepithelial Neoplasia (CIN) grade 2 or more severe detection rate was higher
      for born abroad (age-adj RR 1.65, 95% CI 1.45-1.89). The difference was stronger
      when considering only CIN3 or more severe (age-adj RR 2.29, 95% CI 1.90-2.75).
      Both HPV positivity and CIN2 or more severe detection rate had a different age
      curve in born abroad compared with Italy-born: in the former, the risk was almost
      flat, while in the latter it declined rapidly with age. CONCLUSION: Compliance
      with HPV screening is lower for migrant women, who are affected by higher HPV
      positivity and CIN3 cancer detection rates.

PMID- 25969695
TI  - A new generation of versatile chromogenic substrates for high-throughput analysis
      of biomass-degrading enzymes.
AB  - BACKGROUND: Enzymes that degrade or modify polysaccharides are widespread in pro-
      and eukaryotes and have multiple biological roles and biotechnological
      applications. Recent advances in genome and secretome sequencing, together with
      associated bioinformatic tools, have enabled large numbers of carbohydrate-acting
      enzymes to be putatively identified. However, there is a paucity of methods for
      rapidly screening the biochemical activities of these enzymes, and this is a
      serious bottleneck in the development of enzyme-reliant bio-refining processes.
      RESULTS: We have developed a new generation of multi-coloured chromogenic
      polysaccharide and protein substrates that can be used in cheap, convenient and
      high-throughput multiplexed assays. In addition, we have produced substrates of
      biomass materials in which the complexity of plant cell walls is partially
      maintained. CONCLUSIONS: We show that these substrates can be used to screen the
      activities of glycosyl hydrolases, lytic polysaccharide monooxygenases and
      proteases and provide insight into substrate availability within biomass. We
      envisage that the assays we have developed will be used primarily for first-level
      screening of large numbers of putative carbohydrate-acting enzymes, and the
      assays have the potential to be incorporated into fully or semi-automated robotic
      enzyme screening systems.

PMID- 25969694
TI  - Inpatient and outpatient costs in patients with coronary artery disease and
      mental disorders: a systematic review.
AB  - BACKGROUND: To systematically review in- and outpatient costs in patients with
      coronary artery disease (CAD) and comorbid mental disorders. METHODS: A
      comprehensive database search was conducted for studies investigating persons
      with CAD and comorbid mental disorders (Medline, EMBASE, PsycINFO, Psyndex,
      EconLit, IBSS). All studies were included which allowed a comparison of in- and
      outpatient health care costs (assessed either monetarily or in terms of health
      care utilization) of CAD patients with comorbid mental disorders (mood, anxiety,
      alcohol, eating, somatoform and personality disorders) and those without. Random
      effects meta-analyses were conducted and results reported using forest plots.
      RESULTS: The literature search resulted in 7,275 potentially relevant studies, of
      which 52 met inclusion criteria. Hospital readmission rates were increased in CAD
      patients with any mental disorder (pooled standardized mean difference (SMD) =
      0.34 [0.17;0.51]). Results for depression, anxiety and posttraumatic stress
      disorder pointed in the same direction with heterogeneous SMDs on a primary study
      level ranging from -0.44 to 1.26. Length of hospital stay was not increased in
      anxiety and any mental disorder, while studies on depression reported
      heterogeneous SMDs ranging from -0.08 to 0.82. Most studies reported increased
      overall and outpatient costs for patients with comorbid mental disorders. Results
      for invasive procedures were non-significant respectively inconclusive.
      CONCLUSIONS: Comorbid mental disorders in CAD patients are associated with an
      increased healthcare utilization in terms of higher hospital readmission rates
      and increased overall and outpatient health care costs. From a health care point
      of view, it is requisite to improve the diagnosis and treatment of comorbid
      mental disorders in patients with CAD to minimize incremental costs.

PMID- 25969696
TI  - Terminal 18q deletions are stabilized by neotelomeres.
AB  - BACKGROUND: All human chromosomes are capped by tandem repeat (TTAGGG)n sequences
      that protect them against end-to-end fusion and are essential to chromosomal
      replication and integrity. Therefore, after a chromosomal breakage, the deleted
      chromosomes must be stabilized by retaining the telomere or acquiring a new cap,
      by telomere healing or telomere capture. There are few reports with molecular
      approaches on the mechanisms involved in stabilization of 18q terminal deletions.
      RESULTS: In this study we analyzed nine patients with 18q terminal deletion
      identified by G-banding and genomic array. FISH using PNA probe revealed
      telomeric signals in all deleted chromosomes tested. We fine-mapped breakpoints
      with customized arrays and sequenced six terminal deletion junctions. In all six
      deleted chromosomes sequenced, telomeric sequences were found directly attached
      to the breakpoints. Little or no microhomology was found at the breakpoints and
      none of the breaks sequenced were located in low copy repeat (LCR) regions,
      though repetitive elements were found around the breakpoints in five patients.
      One patient presented a more complex rearrangement with two deleted segments and
      an addition of 17 base pairs (bp). CONCLUSIONS: We found that all six deleted
      chromosomes sequenced were probably stabilized by the healing mechanism leading
      to a neotelomere formation.

PMID- 25969697
TI  - The effects of electronic medical record phenotyping details on genetic
      association studies: HDL-C as a case study.
AB  - BACKGROUND: Biorepositories linked to de-identified electronic medical records
      (EMRs) have the potential to complement traditional epidemiologic studies in
      genotype-phenotype studies of complex human diseases and traits. A major
      challenge in meeting this potential is the use of EMR-derived data to extract
      phenotypes and covariates for genetic association studies. Unlike traditional
      epidemiologic data, EMR-derived data are collected for clinical care and are
      therefore highly variable across patients. The variability of clinical data
      coupled with the challenges associated with searching unstructured clinical notes
      requires the development of algorithms to extract phenotypes for analysis. Given
      the number of possible algorithms that could be developed for any one EMR-derived
      phenotype, we explored here the impact algorithm decision logic has on genetic
      association study results for a single quantitative trait, high density
      lipoprotein cholesterol (HDL-C). RESULTS: We used five different algorithms to
      extract HDL-C from African American subjects genotyped on the Illumina Metabochip
      (n = 11,519) as part of Epidemiologic Architecture for Genes Linked to
      Environment (EAGLE). Tests of association between HDL-C and genetic risk scores
      for HDL-C associated variants suggest that the genetic effect size does not vary
      substantially across the five HDL-C definitions. CONCLUSIONS: These data
      collectively suggest that, at least for this quantitative trait, algorithm
      decision logic and phenotyping details do not appreciably impact genetic
      association study test statistics.

PMID- 25969698
TI  - Comparison between CDC and WHO BMI z-score and their relation with metabolic risk
      markers in Northern Portuguese obese adolescents.
AB  - BACKGROUND: Growth-curves are an important tool for evaluating the anthropometric
      development in pediatrics. The different growth-curves available are based in
      different populations, what leads to different cut-offs. Pediatric obesity tracks
      into adulthood and is associated with increased cardiovascular risk. The accurate
      assessment of a child nutritional status using growth-curves can indicate
      individuals that are either obese or in risk of becoming obese, allowing an early
      intervention. Moreover, the association between the data obtained from growth
      curves with specific metabolic risk factors further highlights the importance of
      these charts. This study aimed to evaluate the associations between body mass
      index z-score (BMIzsc), determined using the growth-curves from the Centre for
      Disease Control and Prevention (CDC) and from the World Health Organization
      (WHO), with cardiovascular risk factors, represented here by metabolic syndrome
      (MS) and insulin resistance (IR) related parameters. The study involved 246 obese
      adolescents (10-18 years, 122 females). MS was defined according to the
      International Diabetes Federation. IR was considered for HOMA-IR greater than
      2.5. FINDINGS: No difference between both BMIzsc in identifying MS was noticeable
      by a ROC analysis. For both indexes the area-under-the-curve increased for older
      groups, particularly for males. CDC-BMIzsc was the best predictor of MS by
      logistic regression when all population was considered, however MS was better
      predicted by WHO-BMIzsc for females and by CDC-BMIzsc for males. Younger girls
      and older boys were in increased risk for MS. Similar results were obtained for
      IR. CONCLUSIONS: A significant difference between the two BMIzsc regarding their
      association with MS and IR was not clear, being these associations weaker in
      younger individuals.

PMID- 25969699
TI  - Development of a process to disclose amyloid imaging results to cognitively
      normal older adult research participants.
AB  - INTRODUCTION: The objective of this study was to develop a process to maximize
      the safety and effectiveness of disclosing Positron Emission Tomography (PET)
      amyloid imaging results to cognitively normal older adults participating in
      Alzheimer's disease secondary prevention studies such as the Anti-Amyloid
      Treatment in Asymptomatic Alzheimer's Disease (A4) Study. METHODS: Using a
      modified Delphi Method to develop consensus on best practices, we gathered and
      analyzed data over three rounds from experts in two relevant fields: informed
      consent for genetic testing or human amyloid imaging. RESULTS: Experts reached
      consensus on (1) text for a brochure that describes amyloid imaging to a person
      who is considering whether to undergo such imaging in the context of a clinical
      trial, and (2) a process for amyloid PET result disclosure within such trials.
      Recommendations included: During consent, potential participants should complete
      an educational session, where they receive verbal and written information
      covering what is known and unknown about amyloid imaging, including possible
      results and their meaning, implications of results for risk of future cognitive
      decline, and information about Alzheimer's and risk factors. Participants should
      be screened for anxiety and depression to determine suitability to receive
      amyloid imaging information. The person conducting the sessions should check
      comprehension and be skilled in communication and recognizing distress. Imaging
      should occur on a separate day from consent, and disclosure on a separate day
      from imaging. Disclosure should occur in person, with time for questions. At
      disclosure, investigators should assess mood and willingness to receive results,
      and provide a written results report. Telephone follow-up within a few days
      should assess the impact of disclosure, and periodic scheduled assessments of
      depression and anxiety, with additional monitoring and follow-up for participants
      showing distress, should be performed. CONCLUSIONS: We developed a document for
      use with potential study participants to describe the process of amyloid imaging
      and the implications of amyloid imaging results; and a disclosure process with
      attention to ongoing monitoring of both mood and safety to receive this
      information. This document and process will be used in the A4 Study and can be
      adapted for other research settings.

PMID- 25969700
TI  - Effect of Change in VO2max on Daily Total Energy Expenditure in a Cohort of
      Norwegian Men: A Randomized Pilot Study.
AB  - OBJECTIVE: To investigate how a change in VO2max induced through 6 weeks of high
      intensity aerobic interval training affects daily total energy expenditure (TEE),
      active energy expenditure (AEE) and mitochondrial function in people not
      previously exposed to structured high intensity aerobic interval training (AIT).
      METHODS: Thirty healthy males (39+/-6 yrs) not exposed to structured exercise
      training were randomized to either 1x4 min AIT (1-AIT), 4x4 min AIT (4-AIT), both
      at 90-95% maximum heart rate (HRmax) or 47 min of MCT at 70% HRmax. TEE, AEE,
      number of steps, active time, sedentary time, VO2max and mitochondrial function
      in m. vastus lateralis were measured before and after intervention. RESULTS: TEE
      increased 14% (p=0.014) and AEE increased 43% (p= 0.004) after MCT. There was no
      change in TEE or AEE after 1-AIT or 4-AIT, but 1-AIT had significantly lower TEE
      (p=0.033) and step-count (p=0.011) compared to MCT post intervention. VO2max
      increased 7% after 1-AIT (p= 0.004) and 9% after 4-AIT (p=0.004), with no change
      after MCT. No change was observed in maximal mitochondrial respiration (VMAX) or
      Citrate Synthase (CS) activity within or between interventions. Basal respiration
      (V0) increased after 1-AIT (p=0.029) and 4-AIT (p=0.022), with no significant
      change after MCT. CONCLUSION: AIT interventions that increase VO2max, do not
      stimulate subjects to increase TEE or AEE. The intensity of exercise seems to
      play apart, as MCT increased TEE and AEE and AIT did not. Emphasis should be
      placed on the importance of maintaining everyday activities when introducing
      structured exercise training to untrained individuals.

PMID- 25969701
TI  - Corrigendum to "reduced oxidative stress contributes to the lipid lowering
      effects of isoquercitrin in free fatty acids induced hepatocytes".

PMID- 25969703
TI  - Hepatitis C genotypes distribution in intravenous drug users in tehran.

PMID- 25969702
TI  - Role of the lipoperoxidation product 4-hydroxynonenal in the pathogenesis of
      severe malaria anemia and malaria immunodepression.
AB  - Oxidative stress plays an important role in the pathogenesis of falciparum
      malaria, a disease still claiming close to 1 million deaths and 200 million new
      cases per year. Most frequent complications are severe anemia, cerebral malaria,
      and immunodepression, the latter being constantly present in all forms of
      malaria. Complications are associated with oxidative stress and lipoperoxidation.
      Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and
      diffusible molecule, forms covalent conjugates with proteins, DNA, and
      phospholipids and modulates important cell functions at very low concentrations.
      Since oxidative stress plays important roles in the pathogenesis of severe
      malaria, it appears important to explore the role of 4-HNE in two important
      malaria complications such as malaria anemia and malaria immunodepression where
      oxidative stress is considered to be involved. In this review we will summarize
      data about 4-HNE chemistry, its biologically relevant chemical properties, and
      its role as regulator of physiologic processes and as pathogenic factor. We will
      review studies documenting the role of 4-HNE in severe malaria with emphasis on
      malaria anemia and immunodepression. Data from other diseases qualify 4-HNE both
      as oxidative stress marker and as pathomechanistically important molecule.
      Further studies are needed to establish 4-HNE as accepted pathogenic factor in
      severe malaria. 

PMID- 25969704
TI  - A rapidly fatal sepsis caused by listeria monocytogenes type-4b in a patient with
      chronic renal failure.
AB  - INTRODUCTION: Listeria monocytogenes is a significant zoonosis causing invasive
      infections in the susceptible persons. The current paper presented a patient who
      died due to a rapidly-progressing multiple organ failure (MOF) as a result of
      severe sepsis caused by L. monocytogenes. CASE PRESENTATION: A 70-years-old
      patient with chronic renal failure was admitted to the infectious diseases clinic
      due to diarrhea for one day. He was hospitalized and the body fluid samples were
      collected for laboratory analyses. Within few hours, his vital findings worsened,
      and he developed respiratory arrest. Ceftriaxone and gentamycin were
      administrated. However, he died due to disseminated intravascular coagulation,
      septic shock and meningoencephalitis at the 22nd hour of admission. Causative
      agent was identified as L. monocytogenes serotype-4b in post-mortem period.
      DISCUSSION: L. monocytogenes can cause progressive and rapidly fatal infections
      in the vulnerable persons, with multisystem involvement. Since this bacterium is
      not susceptible to cephalosporines, it will be better to consider effective
      antimicrobials in the treatment of the possible cases.

PMID- 25969705
TI  - Innovation of High-risk Infants Follow-up Surveillance System in Iran.
AB  - BACKGROUND: Early childhood development is one of the most social determinants of
      health that must be notified in order to reducing social gap and inequity. In
      spite of increasingly developing intensive neonatal care wards and decreasing
      neonatal mortality rate, there is no follow-up surveillance system to identify
      high-risk infants (HRI) and their health problems for timely intervention after
      discharge. This study was carried out to design and pilot high-risk infant follow
      ups (HRIFs) surveillance system, in Alzahra Hospital, a tertiary level center of
      Tabriz University of Medical Sciences (TUOMS), in 2012-2013. METHODS: In this
      qualitative research after studying international documents, consensus about
      criteria of HRIs accomplished by focus group discussion. Then, Delphi agreement
      technique was used to finalizing assessment timetable. In the second phase, we
      piloted the designed surveillance system in Alzahra Hospital, a tertiary level
      center of TUOMS. Pilot study was implemented by follow-up team organized in
      designed model at the first phase of the study. Then, the findings of the pilot
      study were being assessed by an expert panel. If the members agreed on made
      decisions, they were being placed on the agenda of the national committee of
      development care of newborns for final approval. RESULTS: High-risk infants
      follow-up surveillance system was designed in following steps: Defining of
      evidence-based criteria of HRIs, organizing the follow-up team, regulating the
      organs and neurodevelopment assessment timetable, publishing a health certificate
      notebook for HRIs, and designing Access database software for data collection,
      report and evaluation. CONCLUSIONS: We designed and piloted HRIFs surveillance
      system, so this system was institutionalized in Alzahra Hospital, finally. It can
      be prepared to apply in the whole country, after detecting the quantitative
      outcomes and developing the program in East Azarbijan.

PMID- 25969706
TI  - Biomarkers of progression in diabetic nephropathy: The past, present and future.

PMID- 25969707
TI  - Phosphatase and tensin homolog-induced putative kinase 1 and Parkin in diabetic
      heart: Role of mitophagy.
AB  - Diabetes is an independent risk factor for cardiovascular morbidity and
      mortality. Diabetes-associated cardiac pathophysiology is recognized to be due to
      reasons including metabolic consequences on the myocardium. The heart is a highly
      energy-demanding tissue, with mitochondria supplying over 90% of adenosine
      triphosphate. The involvement of mitochondrial dysfunction in diabetes-related
      cardiac pathogenesis has been studied. Phosphatase and tensin homolog-induced
      putative kinase 1 (PINK1) and Parkin, initially identified to be associated with
      the pathogenesis of a familiar form of Parkinson's disease, have recently been
      recognized to play a critical role in mediating cardiomyocytes' adaption to
      stresses. Extensive studies have suggested PINK1 and Parkin as key regulators of
      mitophagy. In the present review article, we will first summarize the new
      findings on PINK1/Parkin acting in cardioprotection, and then discuss the
      potential role of PINK1/Parkin in diabetic heart by mediating mitophagy. 

PMID- 25969708
TI  - Return of the glucoreceptor: Glucose activates the glucose-sensing receptor T1R3
      and facilitates metabolism in pancreatic beta-cells.
AB  - Subunits of the sweet taste receptor, namely T1R2 and T1R3, are expressed in
      mouse pancreatic islets. Quantitatively, the expression of messenger ribonucleic
      acid for T1R2 is much lower than that of T1R3, and immunoreactive T1R2 is in fact
      undetectable. Presumably, a homodimer of T1R3 could function as a signaling
      receptor. Activation of this receptor by adding an artificial sweetener,
      sucralose, leads to an increase in intracellular adenosine triphosphate ([ATP]c).
      This increase in [ATP]c is observed in the absence of ambient glucose. Sucralose
      also augments elevation of [ATP]c induced by methylsuccinate, a substrate for
      mitochondria. Consequently, activation of T1R3 promotes metabolism in
      mitochondria and increases [ATP]c. 3-O-Methylglucose, a non-metabolizable analog
      of glucose, also increases [ATP]c. Conversely, knockdown of T1R3 attenuates
      elevation of [ATP]c induced by glucose. Hence, glucose promotes its own
      metabolism by activating T1R3 and augmenting ATP production. Collectively, a
      homodimer of T1R3 functions as a cell surface glucose-sensing receptor and
      participates in the action of glucose on insulin secretion. The glucose-sensing
      receptor T1R3 might be the putative glucoreceptor proposed decades ago by Niki et
      al. The glucose-sensing receptor is involved in the action of glucose and
      modulates glucose metabolism in pancreatic beta-cells. 

PMID- 25969709
TI  - Possible new therapeutic approach for obesity-related diseases: Role of
      adiponectin receptor agonists.
AB  - Adiponectin is a major adipokine that seems to have a crucial role in the
      protection from many metabolic abnormalities. There have been several reports
      that suggest a strong inverse relationship between plasma levels of adiponectin
      and the severity of obesity and its comorbidities, such as insulin resistance,
      type 2 diabetes and cardiovascular disease. Restoring adiponectin levels has
      salient benefits in many of the obesity-related diseases, which provides a strong
      rationale for adiponectin-based therapeutics for treating metabolic
      abnormalities. A Japanese team of researchers has screened and identified an
      orally active compound that binds to and activates the adiponectin receptor 1
      (AdipoR1) and AdipoR2 receptors that are named AdipRon. This molecule ameliorates
      insulin resistance and glucose intolerance in obese animal models, and also
      extends the shortened lifespan of diabetic obese mice. If this work can be
      extended to humans, the improved safety and efficacy of these orally active
      adiponectin agonists could offer a promising new approach to treating obesity
      related diseases. 

PMID- 25969710
TI  - Incretin action on bone: An added benefit?

PMID- 25969711
TI  - Maternal protein restriction induces early-onset glucose intolerance and alters
      hepatic genes expression in the peroxisome proliferator-activated receptor
      pathway in offspring.
AB  - AIMS/INTRODUCTION: Maternal undernutrition during pregnancy and/or lactation can
      alter the offspring's response to environmental challenges, and thus increases
      the risk of the development of metabolic diseases at a later age. However,
      whether maternal protein restriction can modulate glucose metabolism in the early
      life of offspring is less understood. Furthermore, we explored the potential
      underlying mechanisms that illustrate this phenotype. MATERIALS AND METHODS: To
      test this hypothesis, we examined the offspring of C57BL/6J mice at weaning to
      determine the effects of feeding their mothers a low-protein diet or normal chow
      diet throughout pregnancy and lactation. Gene array experiments and quantitative
      real-time polymerase chain reaction were utilized to explore the altered hepatic
      genes expression. RESULTS: The offspring of dams fed a low-protein diet had a
      lower birthweight and bodyweight, impaired glucose tolerance, decreased insulin
      sensitivity, and decreased serum cholesterol at weaning. Using gene array
      experiments, 253 differentially expressed genes were identified in the liver
      tissues of the offspring between the two groups. Bioinformatic analyses showed
      that all differentially expressed genes were mapped to 11 pathways. We focused on
      the 'peroxisome proliferator-activated receptor signaling pathway,' because
      peroxisome proliferator-activated receptors have emerged as central regulators of
      glucose and lipid homeostasis. Quantitative real-time polymerase chain reaction
      was utilized for the validation of genes in the pathway. CONCLUSIONS: A maternal
      low-protein diet during pregnancy and lactation promotes early-onset glucose
      intolerance in the offspring mice, and the altered hepatic genes expression in
      peroxisome proliferator-activated receptor signaling pathway could play role in
      regulating this phenomenon.

PMID- 25969712
TI  - Comparison of the prevalence of metabolic syndrome and its association with
      diabetes and cardiovascular disease in the rural population of Bangladesh using
      the modified National Cholesterol Education Program Expert Panel Adult Treatment
      Panel III and International Diabetes Federation definitions.
AB  - AIMS/INTRODUCTION: To compare the prevalence of metabolic syndrome (MS) using the
      modified National Cholesterol Education Program Adult Treatment Plan III (NCEP)
      and the International Diabetes Federation (IDF) definitions and, using both
      definitions, determine and compare the association of MS, prediabetes, type 2
      diabetes, hypertension (HTN) and cardiovascular disease risk (CVD). MATERIALS AND
      METHODS: A total of 2,293 randomly selected participants (aged >=20 years) in a
      rural community in Bangladesh were investigated in a population-based cross
      sectional study. Sociodemographic and anthropometric characteristics, blood
      pressure, blood glucose, and lipid profiles were studied. Age-adjusted data for
      MS and cardiometabolic risk factors were assessed, and their relationships were
      examined. RESULTS: The age-adjusted prevalence of MS was 30.7% (males 30.5%;
      females 30.5%) using the NCEP definition, and 24.5% (males 19.2%, females 27.5%)
      using the IDF definition. The prevalence of MS using the NCEP definition was also
      higher in study participants with prediabetes, type 2 diabetes, HTN and CVD risk.
      The agreement rate between both definitions was 92% (k = 0.80). The NCEP
      definition had a stronger association with type 2 diabetes and HTN (odds ratio
      12.4 vs 5.2; odds ratio 7.0 vs 4.7, respectively) than the IDF definition.
      However, the odds ratios for prediabetes and CVD risk were not significantly
      different. CONCLUSIONS: The prevalence of MS was higher using the NCEP
      definition, and was more strongly associated with prediabetes, type 2 diabetes,
      HTN and CVD in this Bangladeshi population.

PMID- 25969713
TI  - Trajectory of body mass index before the development of type 2 diabetes in
      Japanese men: Toranomon Hospital Health Management Center Study 15.
AB  - AIMS/INTRODUCTION: We aimed to investigate the long-term trajectory of general
      adiposity assessed by the body mass index (BMI) before the onset of type 2
      diabetes in Japanese individuals. MATERIALS AND METHODS: We retrospectively
      examined data on 1,553 Japanese men without diabetes. Mean BMI and incident cases
      of diabetes (diabetes indicated by fasting glucose concentrations >=7.0 mmol/L, a
      self-reported history of clinician-diagnosed diabetes, or glycated hemoglobin
      >=6.5% (>=48 mmol/mol) were assessed on an annual basis over a 10-year period
      after the baseline examination. RESULTS: Mean (standard deviation) BMI at the
      time of diagnosis was 24.4 kg/m(2) (3.1 kg/m(2)) among cases of diabetes (n =
      191). An increasingly high BMI was associated with the early stage of the disease
      development, such as an 8- to 10-year prediagnosis period; individuals who
      developed diabetes experienced a prolonged and stable elevated BMI of >=24.4
      kg/m(2) over the 8 years before the diagnosis of diabetes. The mean BMI among the
      non-cases of diabetes did not exceed 23.2 kg/m(2) throughout the period.
      CONCLUSIONS: These results suggested that Japanese men who eventually developed
      diabetes during the 10-year observation period were not characterized as obese,
      but had stable high-normal BMIs before the onset of diabetes. Previous evidence
      showed that values for glycemic markers rapidly increased before the development
      of diabetes; however, the present study showed a slight gain in BMI in the
      earlier stage of the natural history of diabetes followed by a prolonged period
      of overweight.

PMID- 25969714
TI  - Association of variants in CDKN2A/2B and CDKAL1 genes with gestational insulin
      sensitivity and disposition in pregnant Han Chinese women.
AB  - AIMS/INTRODUCTION: Variants in cell cycle regulation genes, CDKAL1 and CDKN2A/2B,
      have been suggested to be associated with type 2 diabetes, and also play a role
      in insulin procession in non-diabetic European individuals. Rs7754580 in CDKAL1
      and rs7020996 in CDKN2A/2B were found to be associated with gestational diabetes
      in Chinese individuals. In order to understand the metabolism mechanism of
      greatly upregulated maternal insulin signaling during pregnancy and the
      pathogenesis of gestational diabetes, we investigated the impact of rs7754580 and
      rs7020996 on gestational insulin regulation and procession. MATERIALS AND
      METHODS: We recruited 1,146 unrelated, non-diabetic, pregnant Han Chinese women
      (age 28.5 +/- 4.1 years, body mass index 21.4 +/- 2.6 kg/m(2)), and gave them
      oral glucose tolerance tests. The indices of insulin sensitivity, insulin
      disposition, insulin release and proinsulin to insulin conversion were
      calculated. Rs7754580 in the CDKAL1 gene and rs7020996 in the CDKN2A/2B gene were
      genotyped. Under an additive model, we analyzed the associations between the
      variants and gestational insulin indices using logistic regression. RESULTS: By
      adjusting for maternal age, body mass index and the related interactions, CDKAL1
      rs7754580 risk allele C was detected to be associated with increased insulin
      sensitivity (P = 0.011), decreased insulin disposition (P = 0.0002) and 2-h
      proinsulin conversion (P = 0.017). CDKN2A/2B rs7020996 risk allele T was found to
      be related to decreased insulin sensitivity (P = 0.002) and increased insulin
      disposition (P = 0.0001). CONCLUSIONS: The study showed that cell cycle
      regulating genes might have a distinctive effect on gestational insulin
      sensitivity, beta-cell function and proinsulin conversion in pregnant Han Chinese
      women.

PMID- 25969715
TI  - Enteral supplementation with glutamine, fiber, and oligosaccharide modulates
      incretin and glucagon-like peptide-2 secretion.
AB  - AIMS/INTRODUCTION: A dietary supplementation product enriched with glutamine,
      dietary fiber and oligosaccharide (GFO) is widely applied for enteral nutrition
      support in Japan. The aim of the present study was to evaluate the effects of GFO
      ingestion on secretion of incretins, gastric inhibitory polypeptide (GIP) and
      glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2). MATERIALS
      AND METHODS: We carried out a cross-over study involving 20 healthy Japanese
      volunteers. The participants received GFO or 17 g of glucose, the equivalent
      carbohydrate in GFO as the control. Plasma glucose, serum insulin, and plasma
      total GIP, total GLP-1 and total GLP-2 levels during GFO or glucose loading were
      determined. RESULTS: GFO loading produced significantly higher plasma GLP-1
      levels at 30 min and 60 min, area under the curve-GLP-1 value, and area under the
      curve-GLP-2 value after administration compared with those by glucose loading. In
      contrast, plasma GIP levels at both 30 and 60 min, and area under the curve-GIP
      value after glucose loading were significantly higher than those after GFO
      loading. CONCLUSIONS: These results show that GFO ingestion stimulates GLP-1 and
      GLP-2 secretion, and reduces GIP secretion compared with glucose ingestion.
      Therefore, GFO could have an intestinotrophic effect as well as an ameliorating
      effect on metabolic disorders through modification of release of gut hormones.

PMID- 25969716
TI  - Evaluation of the fatty liver index as a predictor for the development of
      diabetes among insurance beneficiaries with prediabetes.
AB  - AIMS/INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common
      liver disease in developed countries, and it was required to monitor patients
      with prediabetes. However, there have been few reports establishing the risk for
      diabetes mellitus (DM) among patients with prediabetes. The purpose of the
      present study was to evaluate the effect of NAFLD on the progression of DM among
      insurance beneficiaries with prediabetes, using data from specific health check
      ups and the fatty liver index (FLI). MATERIALS AND METHODS: We used a
      retrospective cohort study that enrolled 967 insurance beneficiaries with
      prediabetes who had rarely drunk or could not drink alcohol, or whose alcohol
      consumption was <19 g/day from two health insurance societies. We divided
      insurance beneficiaries into FLI <30, intermediates FLIs and FLI >=60, and
      compared the incidence rate of DM among the groups after 3 years' follow up,
      using multiple logistic regression models. RESULTS: During 3 years' follow up,
      progression of diabetes was seen in 65 men (11.5%) and 24 women (6.0%). Logistic
      regression analyses showed that those with NAFLD had significantly higher risks
      of developing DM; this was the case in both men (odds ratio 2.68, 95%
      confidential interval 1.29-5.56) and women (odds ratio 10.35, 95% confidential
      interval 3.22-33.31). CONCLUSIONS: Among insurance beneficiaries with
      prediabetes, those with NAFLD had a significantly higher risk of DM than those
      without NAFLD. The FLI might be useful for detecting individuals who have an
      especially higher risk for DM, and developing more effective guidance for
      delivering healthcare services in Japan.

PMID- 25969717
TI  - Assessment of glycemic control in patients with type 2 diabetes mellitus treated
      with metformin-sulfonylurea combination: Results of a multicenter, cross
      sectional, observational study in Korea.
AB  - AIMS/INTRODUCTION: To assess the current status of glycemic control in patients
      with type 2 diabetes treated with a combination of metformin and sulfonylurea for
      >3 months, as measured by glycosylated hemoglobin (HbA1c). MATERIALS AND METHODS:
      Data on patient demographics, diabetic complications, HbA1c, fasting plasma
      glucose (FPG) and type of treatment were collected in this multicenter, cross
      sectional, non-interventional study. RESULTS: From April 2008 to February 2009,
      5,628 patients were recruited from 299 centers in Korea. Patients characteristics
      (mean +/- SD) were as follows: age 58.4 +/- 10.8 years, duration of diabetes 6.1
      +/- 4.7 years, body mass index 24.7 +/- 2.9 kg/m(2), HbA1c 7.77 +/- 1.22%, FBG
      147.4 +/- 46.5 mmol/L and FPG 164.0 +/- 54.3 mmol/L. The most common diabetic
      complication was neuropathy (22.5%), followed by retinopathy (18.3%) and
      microalbuminuria (16.1%). Just 1,524 (27.1%) patients achieved HbA1c <=7%. A
      higher number of patients (32.6%) treated by endocrinologists achieved HbA1c <=7%
      than those treated by internists (24.4%) and primary care physicians (23.2%). In
      multivariate analyses, diabetic retinopathy (odds ratio 0.455, 95% confidence
      interval 0.341-0.606), nephropathy (odds ratio 0.639, 95% confidence interval
      0.43-0.949), diabetes for >=5 years (odds ratio 0.493, 95% confidence interval
      0.4-0.606) and older age added by 1 year (odds ratio 1.019, 95% confidence
      interval 1.01-1.029) was significantly associated with achieving target HbA1c. In
      addition, treatment by endocrinologists rather than internists significantly
      increased chances of achieving target HbA1c (odds ratio 1.417, 95% confidence
      interval 1.146-1.751). CONCLUSIONS: The majority of patients with type 2 diabetes
      in Korea had inadequate glycemic control, despite receiving a combination of
      metformin and sulfonylurea.

PMID- 25969718
TI  - Ezetimibe combined with standard diet and exercise therapy improves insulin
      resistance and atherosclerotic markers in patients with metabolic syndrome.
AB  - AIMS/INTRODUCTION: Ezetimibe lowers serum lipid levels by inhibiting intestinal
      absorption of dietary and biliary cholesterol. However, the effect of ezetimibe
      on insulin resistance remains unclear. The aim of the present study was to
      examine this issue in patients with metabolic syndrome in local-dwelling
      Japanese, who were not being treated with lipid-lowering drugs. MATERIALS AND
      METHODS: In 2009, 1,943 participants received a health examination in the
      Tanushimaru Study, a Japanese cohort of the Seven Countries Study, of whom 490
      participants had metabolic syndrome. Among them, 61 participants (41 men and 20
      women) were examined in the present study. They were treated with 10 mg of
      ezetimibe once a day for 24 weeks, combined with standard diet and exercise
      therapy. RESULTS: Bodyweight (P < 0.001), body mass index (P < 0.001), systolic
      blood pressure (P = 0.003), diastolic blood pressure (P < 0.001), triglycerides
      (P = 0.002), non-high-density lipoprotein cholesterol (P = 0.001), low-density
      lipoprotein cholesterol (P < 0.001) and homeostasis model assessment of insulin
      resistance (P = 0.011) significantly decreased after the observational period.
      There were no statistically significant differences in the effects of ezetimibe
      between men and women. Univariate analysis showed that the reduction of
      homeostasis model assessment of insulin resistance was not associated with the
      improvement of other metabolic components. CONCLUSIONS: Ezetimibe combined with
      standard diet and exercise therapy improves not only bodyweight and atherogenic
      lipid profiles, but also insulin resistance, blood pressure and anthropometric
      factors in metabolic syndrome in local-dwelling Japanese. Interestingly, the
      improvement of insulin resistance had no correlation with other metabolic
      components.

PMID- 25969719
TI  - Morphological changes of the peripheral nerves evaluated by high-resolution
      ultrasonography are associated with the severity of diabetic neuropathy, but not
      corneal nerve fiber pathology in patients with type 2 diabetes.
AB  - AIMS/INTRODUCTION: To evaluate the morphological changes of the median and
      posterior tibial nerve using high-resolution ultrasonography, and the corneal C
      fiber pathology by corneal confocal microscopy in type 2 diabetic patients.
      MATERIALS AND METHODS: The cross-sectional area, hypoechoic area and maximum
      thickness of the nerve fascicle of both nerves were measured by high-resolution
      ultrasonography in 200 type 2 diabetic patients, stratified by the severity of
      diabetic neuropathy, and in 40 age- and sex-matched controls. These parameters
      were associated with corneal C fiber pathology visualized by corneal confocal
      microscopy, neurophysiological tests and severity of diabetic neuropathy.
      RESULTS: The cross-sectional area, hypoechoic area and maximum thickness of the
      nerve fascicle of both nerves in patients without diabetic neuropathy were larger
      than those in control subjects (P < 0.05 to P < 0.001), and further increased
      relative to the severity of neuropathy (P < 0.0001). All morphological changes of
      both nerves were negatively associated with motor and sensory nerve conduction
      velocity (P = 0.01 to P < 0.0001), and directly associated with 2,000-Hz current
      perception threshold (P = 0.009 to P < 0.001). The significant corneal C fiber
      pathology occurred before developing the neuropathy, and deteriorated only in
      patients with the most severe neuropathy. The association between the
      morphological changes of both nerves and corneal C fiber pathology was poor.
      CONCLUSIONS: The morphological changes in peripheral nerves of type 2 diabetic
      patients were found before the onset of neuropathy, and were closely correlated
      with the severity of diabetic neuropathy, but not with corneal C fiber pathology.

PMID- 25969720
TI  - Rapid onset of syndrome of inappropriate antidiuretic hormone secretion induced
      by duloxetine in an elderly type 2 diabetic patient with painful diabetic
      neuropathy.
AB  - Diabetic neuropathy is the most common diabetic complication. Duloxetine, a
      serotonin noradrenaline reuptake inhibitor (SNRI), is widely used for the
      treatment of diabetic painful neuropathy (DPN) because of the efficacy and safety
      profile. Syndrome of inappropriate antidiuretic hormone secretion, which is
      strongly associated duloxetine, is a rare but occasionally life-threatening
      adverse effect. Here, we report a case of syndrome of inappropriate antidiuretic
      hormone secretion that rapidly developed after starting duloxetine in an elderly
      Japanese female type 2 diabetes mellitus patient. Furthermore, we discuss the
      possible relationship between the onset of syndrome of inappropriate antidiuretic
      hormone secretion and the gene polymorphism of cytochrome P450 isoform 1A2 and
      2D6, both of which are responsible for duloxetine metabolism. 

PMID- 25969721
TI  - Renoprotective effects of atorvastatin compared with pravastatin on progression
      of early diabetic nephropathy.
AB  - INTRODUCTION: Several studies have shown that statins suppress the progression of
      diabetic nephropathy. However, few reports have directly compared the
      renoprotective effects between potent and conventional statins. MATERIALS AND
      METHODS: Patients with diabetic nephropathy, selected as those with a serum
      creatinine level of 0.9-1.5 mg/dL and simultaneously having either
      microalbuminuria or positive proteinuria, were randomly assigned to one of three
      groups: a conventional diet therapy group, a group given 10 mg of pravastatin and
      a group given 10 mg of atorvastatin. Renal function was evaluated before and
      after a 12-month period of therapy. RESULTS: The atorvastatin group had a
      significant decrease in low-density lipoprotein cholesterol at 3 months and
      thereafter compared with the other groups. The urinary albumin-to-creatinine
      ratio significantly decreased in the atorvastatin group; the degree of this
      decrease was significantly greater than that in the diet therapy group. The
      kidney function estimated with cystatin C (CysC) and the estimated glomerular
      filtration rate calculated from CysC were significantly preserved in the
      atorvastatin group compared with the pravastatin group. In a multivariate
      regression analysis, the use of atorvastatin was the only explanatory variable
      for the changes in CysC; this was independent of changes in low-density
      lipoprotein cholesterol. CONCLUSIONS: Atorvastatin is more effective than
      pravastatin for the prevention of increase in CysC, and this renoprotective
      effect was considered to a result of the pleiotropic effect of atorvastatin
      independent of its lipid-lowering effect. This study was registered with UMIN
      (no. UMIN 000001774).

PMID- 25969722
TI  - High-normal urinary albumin-to-creatinine ratio is independently associated with
      metabolic syndrome in Chinese patients with type 2 diabetes mellitus: A cross
      sectional community-based study.
AB  - AIMS/INTRODUCTION: Microalbuminuria is positively related to metabolic syndrome
      (MetS). Our aim was to investigate whether urinary albumin-to-creatinine ratio
      (UACR) within the normal range is independently associated with MetS in Chinese
      community-based patients with type 2 diabetes. MATERIALS AND METHODS: A total of
      514 participants (206 males and 308 females; mean age 66 years) with UACR less
      than 3.5 mg/mmol were enrolled from two downtown areas of Shanghai. The
      participants were stratified into quartiles according to UACR levels. The
      prevalence of MetS was assessed and compared among the four groups by binary
      logistic regression. RESULTS: Compared with participants with UACRs in the first
      quartile, the other quartiles had a higher prevalence of MetS (65.9%, 74.4% and
      81.3%, respectively, P = 0.001) after adjustment for sex and age. After adjusting
      for potential confounders, participants in the second to the fourth quartile
      group had a 1.36-, 1.84- and 2.73-fold risk of MetS, respectively, relative to
      those in the lowest quartile. Furthermore, UACR, whether as quartile groups or as
      a continuous variable, is an independent predictor of MetS after fully adjusting
      for other variables. CONCLUSIONS: These results suggest that UACR even within the
      normal range is independently associated with MetS in Chinese community-based
      patients with type 2 diabetes mellitus.

PMID- 25969723
TI  - Association between sugar-sweetened beverages and type 2 diabetes: A meta
      analysis.
AB  - AIMS/INTRODUCTION: Many studies have been carried out to examine the association
      between sugar-sweetened beverages and the incident of type 2 diabetes, but
      results are mixed. The aim of the present study was to estimate the association
      between sugar-sweetened beverage intake and the risk of type 2 diabetes.
      MATERIALS AND METHODS: PubMed, Springer Link and Elsevier databases were searched
      up to July 2014. Prospective studies published on the association between sugar
      sweetened beverage intake and the risk of type 2 diabetes were included. The
      pooled relative risks (RRs) and 95% confidence intervals (CIs) for highest versus
      lowest category of sugar-sweetened beverages were estimated using a random
      effects model. RESULTS: The pooled effect estimate of sugar-sweetened beverage
      intake was 1.30 (95% confidence interval [CI] 1.21-1.39) for type 2 diabetes;
      stratified by geographic region of the studies, the pooled effect estimates were
      1.34 (95% CI 0.74-2.43), 1.30 (95% CI 1.20-1.40), 1.29 (95% CI 1.09-1.53) in
      Asia, the USA and Europe,respectively; the pooled effect estimates were 1.26 (95%
      CI 1.16-1.36) with adjusting body mass index and 1.38 (95% CI 1.23-1.56) without
      adjusting body mass index. CONCLUSIONS: Our findings suggested that sugar
      sweetened beverage intake was associated with an increased risk of type 2
      diabetes, and the association was attenuated by adjustment for body mass index.
      Specifically, the associations were also found to be significantly positive in
      the USA and Europe.

PMID- 25969724
TI  - Case of newly onset type 1 diabetes after highly active antiretroviral therapy
      against HIV infection.

PMID- 25969727
TI  - Eight years tumor control with pazopanib for a metastatic resistant epithelioid
      hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma is a rare connective tissue tumor of vascular
      origin. It is most commonly found in young to middle aged women, and its clinical
      behavior is remakably variable from an indolent metastatic tumor to an aggressive
      rapidly growing neoplasm. Most tumors are diagnosed in an advanced unresectable
      phase and when clinically aggressive, require systemic cytotoxic treatment of
      sarcoma. Then, the 5-year survival rate after chemotherapy does not exceed 30%.
      Antiangiogenics are active in selected sarcoma subtypes: pazopanib, the only anti
      angiogenic registered agent for sarcoma provides a median PFS of 4.5 months only
      in the pivotal study. Their activity in EHE has been reported but long term
      outcome of these patients remain unreported. We report a case of a female patient
      with HEH who was treated with pazopanib for almost 8 years. Pazopanib therapy
      resulted in clinical improvement of symptoms and durable stabilization of liver
      tumors and lung lesions. CONCLUSION: Pazopanib is a promising therapeutic option
      in patients with HEH.

PMID- 25969726
TI  - Integrated analysis of whole-exome sequencing and transcriptome profiling in
      males with autism spectrum disorders.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental
      disorders with high heritability. Recent findings support a highly heterogeneous
      and complex genetic etiology including rare de novo and inherited mutations or
      chromosomal rearrangements as well as double or multiple hits. METHODS: We
      performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in
      a subset of male patients with idiopathic ASD (n = 36) in order to identify
      causative genes, transcriptomic alterations, and susceptibility variants.
      RESULTS: We detected likely monogenic causes in seven cases: five de novo (SCN2A,
      MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and
      CDKL5). Transcriptomic analyses allowed the identification of intronic causative
      mutations missed by the usual filtering of WES and revealed functional
      consequences of some rare mutations. These included aberrant transcripts (PTEN,
      POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2,
      ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense
      mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed
      enrichment in relevant pathways such as the PI3K-Akt signaling and the axon
      guidance. CONCLUSIONS: Integrative analysis of WES and blood RNAseq data has
      proven to be an efficient strategy to identify likely monogenic forms of ASD (19%
      in our cohort), as well as additional rare inherited mutations that can
      contribute to ASD risk in a multifactorial manner. Blood transcriptomic data,
      besides validating 88% of expressed variants, allowed the identification of
      missed intronic mutations and revealed functional correlations of genetic
      variants, including changes in splicing, expression levels, and allelic
      expression.

PMID- 25969728
TI  - Improving the ostrich genome assembly using optical mapping data.
AB  - BACKGROUND: The ostrich (Struthio camelus) is the tallest and heaviest living
      bird. Ostrich meat is considered a healthy red meat, with an annual worldwide
      production ranging from 12,000 to 15,000 tons. As part of the avian phylogenomics
      project, we sequenced the ostrich genome for phylogenetic and comparative
      genomics analyses. The initial Illumina-based assembly of this genome had a
      scaffold N50 of 3.59 Mb and a total size of 1.23 Gb. Since longer scaffolds are
      critical for many genomic analyses, particularly for chromosome-level comparative
      analysis, we generated optical mapping (OM) data to obtain an improved assembly.
      The OM technique is a non-PCR-based method to generate genome-wide restriction
      enzyme maps, which improves the quality of de novo genome assembly. FINDINGS: In
      order to generate OM data, we digested the ostrich genome with KpnI, which
      yielded 1.99 million DNA molecules (>250 kb) and covered the genome at least
      500*. The pattern of molecules was subsequently assembled to align with the
      Illumina-based assembly to achieve sequence extension. This resulted in an OM
      assembly with a scaffold N50 of 17.71 Mb, which is 5 times as large as that of
      the initial assembly. The number of scaffolds covering 90% of the genome was
      reduced from 414 to 75, which means an average of ~3 super-scaffolds for each
      chromosome. Upon integrating the OM data with previously published FISH
      (fluorescence in situ hybridization) markers, we recovered the full PAR
      (pseudoatosomal region) on the ostrich Z chromosome with 4 super-scaffolds, as
      well as most of the degenerated regions. CONCLUSIONS: The OM data significantly
      improved the assembled scaffolds of the ostrich genome and facilitated chromosome
      evolution studies in birds. Similar strategies can be applied to other genome
      sequencing projects to obtain better assemblies.

PMID- 25969729
TI  - A neglected priority? The importance of surgery in tackling global health
      inequalities.

PMID- 25969730
TI  - Barriers and facilitators to the quality use of essential medicines for maternal
      health in low-resource countries: An Ishikawa framework.
AB  - BACKGROUND: An estimated 800 women die every day due to complications related to
      pregnancy or childbirth. Complications such as postpartum haemorrhage (PPH) and
      pre-eclampsia and eclampsia can be prevented by the appropriate use of essential
      medicines. The objective of this study was to identify the common barriers and
      facilitators to the availability and use of oxytocin, ergometrine, and magnesium
      sulfate (MgSO4) - essential medicines indicated for the prevention and treatment
      of PPH and pre-eclampsia and eclampsia. METHODS: We analyzed seven UNFPA/WHO
      reports published in 2008-2010. These reports summarized country-wide rapid
      assessments of access to and use of essential medicines for maternal health in
      Mongolia, Nepal, Laos, the Democratic People's Republic of Korea (DPRK), the
      Philippines, Vanuatu, and the Solomon Islands. We used a "fishbone" (Ishikawa)
      diagram as the analytic framework to identify facilitators and barriers at four
      health-system levels: government/regulatory, pharmaceutical supply, health
      facility, and health professional. RESULTS: Common facilitators to the quality
      use of essential medicines for maternal health were observed at the
      government/regulatory and health professional level. A majority of countries had
      these medicines listed in their essential medicines lists. Awareness of the
      medicines was generally high among health professionals. Common barriers were
      identified at all health-system levels. First, standard treatment guidelines were
      not available, updated, or standardized. Second, there was an inadequate capacity
      to forecast and procure medicines. Third, a required MgSO4 antidote was often not
      available and the storage conditions for oxytocin were deficient. CONCLUSIONS:
      The "fishbone" Ishikawa diagram is a useful tool for describing the findings of
      rapid assessments of quality use of essential medicines for maternal health
      across countries. The facilitators and barriers identified should guide the
      development of tailored intervention programs to improve and expand the use of
      these life-saving medicines.

PMID- 25969731
TI  - Impact of global health governance on country health systems: the case of HIV
      initiatives in Nigeria.
AB  - BACKGROUND: Three global health initiatives (GHIs) - the US President's Emergency
      Plan for AIDS Relief, the Global Fund to Fight AIDS, Tuberculosis and Malaria,
      and the World Bank Multi-Country HIV/AIDS Program - finance most HIV services in
      Nigeria. Critics assert that GHIs burden fragile health systems in resource-poor
      countries and that health system limitations in these countries constrain the
      achievement of the objectives of GHIs. This study analyzed interactions between
      HIV GHIs and the Nigerian Health System and explored how the impact of the GHIs
      could be optimized. METHODS: A country case study was conducted using qualitative
      methods, including: semi-structured interviews, direct observation, and archival
      review. Semi-structured interviews were held with key informants selected to
      reach a broad range of stakeholders including policymakers, program managers,
      service providers, representatives of donor agencies and their implementing
      partners; the WHO country office in Nigeria; independent consultants; and civil
      society organizations involved in HIV work. The fieldwork was conducted between
      June and August 2013. FINDINGS: HIV GHIs have had a mixed impact on the health
      system. They have enhanced availability of and access to HIV services, improved
      quality of services, and strengthened health information systems and the role of
      non-state actors in health care. On the negative end, HIV donor funding has
      increased dependency on foreign aid, widened disparities in access to HIV
      services, done little to address the sustainability of the services, crowded out
      non-HIV health services, and led to the development of a parallel supply
      management system. They have also not invested significantly in the production of
      new health workers and have not addressed maldistribution problems, but have
      rather contributed to internal brain drain by luring health workers from the
      public sector to non-governmental organizations and have increased workload for
      existing health workers. There is poor policy direction, strategic planning and
      coordination, and regulation of externally-financed HIV programs by the
      government and this poses a great limitation to the optimal use of HIV-specific
      foreign aid in Nigeria. CONCLUSIONS: A few reforms are necessary to improve the
      strengthening effect of GHIs and to minimize their negative and unintended
      consequences. This will require stronger leadership from the Nigerian government
      with regards to better coordination of externally-financed health programs. Also,
      donors need to play a greater role in addressing the negative consequences of
      foreign aid. The findings highlight important unintended consequences and system
      wide impacts that get little attention in traditional program evaluation.

PMID- 25969732
TI  - Prevalence of rheumatoid arthritis in low- and middle-income countries: A
      systematic review and analysis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder that affects the
      small joints of the body. It is one of the leading causes of chronic morbidity in
      high-income countries, but little is known about the burden of this disease in
      low- and middle-income countries (LMIC). METHODS: The aim of this study was to
      estimate the prevalence of RA in six of the World Health Organization's (WHO)
      regions that harbour LMIC by identifying all relevant studies in those regions.
      To accomplish this aim various bibliographic databases were searched: PubMed,
      EMBASE, Global Health, LILACS and the Chinese databases CNKI and WanFang. Studies
      were selected based on pre-defined inclusion criteria, including a definition of
      RA based on the 1987 revision of the American College of Rheumatology (ACR)
      definition. RESULTS: Meta-estimates of regional RA prevalence rates for countries
      of low or middle income were 0.40% (95% CI: 0.23-0.57%) for Southeast Asian,
      0.37% (95% CI: 0.23-0.51%) for Eastern Mediterranean, 0.62% (95% CI: 0.47-0.77%)
      for European, 1.25% (95% CI: 0.64-1.86%) for American and 0.42% (95% CI: 0.30
      0.53%) for Western Pacific regions. A formal meta-analysis could not be performed
      for the sub-Saharan African region due to limited data. Male prevalence of RA in
      LMIC was 0.16% (95% CI: 0.11-0.20%) while the prevalence in women reached 0.75%
      (95% CI: 0.60-0.90%). This difference between males and females was statistically
      significant (P < 0.0001). The prevalence of RA did not differ significantly
      between urban and rural settings (P = 0.353). These prevalence estimates
      represent 2.60 (95% CI: 1.85-3.34%) million male sufferers and 12.21 (95% CI:
      9.78-14.67%) million female sufferers in LMIC in the year 2000, and 3.16 (95% CI:
      2.25-4.05%) million affected males and 14.87 (95% CI: 11.91-17.86%) million
      affected females in LMIC in the year 2010. CONCLUSION: Given that majority of the
      world's population resides in LMIC, the number of affected people is substantial,
      with a projection to increase in the coming years. Therefore, policy makers and
      health-care providers need to plan to address a significant disease burden both
      socially and economically.

PMID- 25969734
TI  - Direct estimates of national neonatal and child cause-specific mortality
      proportions in Niger by expert algorithm and physician-coded analysis of verbal
      autopsy interviews.
AB  - BACKGROUND: This study was one of a set of verbal autopsy investigations
      undertaken by the WHO/UNCEF-supported Child Health Epidemiology Reference Group
      (CHERG) to derive direct estimates of the causes of neonatal and child deaths in
      high priority countries of sub-Saharan Africa. The objective of the study was to
      determine the cause distributions of neonatal (0-27 days) and child (1-59 months)
      mortality in Niger. METHODS: Verbal autopsy interviews were conducted of random
      samples of 453 neonatal deaths and 620 child deaths from 2007 to 2010 identified
      by the 2011 Niger National Mortality Survey. The cause of each death was assigned
      using two methods: computerized expert algorithms arranged in a hierarchy and
      physician completion of a death certificate for each child. The findings of the
      two methods were compared to each other, and plausibility checks were conducted
      to assess which is the preferred method. Comparison of some direct measures from
      this study with CHERG modeled cause of death estimates are discussed. FINDINGS:
      The cause distributions of neonatal deaths as determined by expert algorithms and
      the physician were similar, with the same top three causes by both methods and
      all but two other causes within one rank of each other. Although child causes of
      death differed more, the reasons often could be discerned by analyzing
      algorithmic criteria alongside the physician's application of required minimal
      diagnostic criteria. Including all algorithmic (primary and co-morbid) and
      physician (direct, underlying and contributing) diagnoses in the comparison
      minimized the differences, with kappa coefficients greater than 0.40 for five of
      11 neonatal diagnoses and nine of 13 child diagnoses. By algorithmic diagnosis,
      early onset neonatal infection was significantly associated (chi(2) = 13.2, P <
      0.001) with maternal infection, and the geographic distribution of child
      meningitis deaths closely corresponded with that for meningitis surveillance
      cases and deaths. CONCLUSIONS: Verbal autopsy conducted in the context of a
      national mortality survey can provide useful estimates of the cause distributions
      of neonatal and child deaths. While the current study found reasonable agreement
      between the expert algorithm and physician analyses, it also demonstrated greater
      plausibility for two algorithmic diagnoses and validation work is needed to
      ascertain the findings. Direct, large-scale measurement of causes of death
      complement, can strengthen, and in some settings may be preferred over modeled
      estimates.

PMID- 25969733
TI  - Geographic epidemiology of cardiometabolic risk factors in middle class urban
      residents in India: cross-sectional study.
AB  - OBJECTIVE: To determine epidemiology of cardiovascular risk factors according to
      geographic distribution and macrolevel social development index among urban
      middle class subjects in India. METHODS: We performed cross-sectional surveys in
      11 cities in India during years 2005-2009. 6198 subjects aged 20-75 years (men
      3426, women 2772, response 62%) were evaluated for cardiovascular risk factors.
      Cities were grouped according to geographic distribution into northern (3 cities,
      n = 1321), western (2 cities, n = 1814), southern (3 cities, n = 1237) and
      eastern (3 cities, n = 1826). They were also grouped according to human social
      development index into low (3 cities, n = 1794), middle (5 cities, n = 2634) and
      high (3 cities, n = 1825). Standard definitions were used to determine risk
      factors. Differences in risk factors were evaluated using chi(2) test. Trends
      were examined by least squares regression. FINDINGS: Age-adjusted prevalence (95%
      confidence intervals) of various risk factors was: low physical activity 42.1%
      (40.9-43.3), high dietary fat 49.9% (47.8-52.0), low fruit/vegetables 26.9% (25.8
      28.0), smoking 10.1% (9.1-11.1), smokeless tobacco use 9.8% (9.1-10.5),
      overweight 42.9% (41.7-44.1), obesity 11.6% (10.8-12.4), high waist circumference
      45.5% (44.3-46.7), high waist-hip ratio 75.7% (74.7-76.8), hypertension 31.6%
      (30.4-32.8), hypercholesterolemia 25.0% (23.9-26.9), low HDL cholesterol 42.5%
      (41.3-43.7), hypertriglyceridemia 36.9% (35.7-38.1), diabetes 15.7% (14.8-16.6),
      and metabolic syndrome 35.7% (34.5-36.9). Compared with national average,
      prevalence of most risk factors was not significantly different in various
      geographic regions, however, cities in eastern region had significantly lower
      prevalence of overweight, hypertension, hypercholesterolemia, diabetes and
      metabolic syndrome compared with other regions (P < 0.05 for various
      comparisons). It was also observed that cities with low human social development
      index had lowest prevalence of these risk factors in both sexes (P < 0.05).
      CONCLUSIONS: Urban middle-class men and women in eastern region of India have
      significantly lower cardiometabolic risk factors compared to northern, western
      and southern regions. Low human social development index cities have lower risk
      factor prevalence.

PMID- 25969735
TI  - Cross-fostering immediately after birth induces a permanent microbiota shift that
      is shaped by the nursing mother.
AB  - BACKGROUND: Current research has led to the appreciation that there are
      differences in the commensal microbiota between healthy individuals and
      individuals that are predisposed to disease. Treatments to reverse disease
      pathogenesis through the manipulation of the gastrointestinal (GI) microbiota are
      now being explored. Normalizing microbiota between different strains of mice in
      the same study is also needed to better understand disease pathogenesis. Current
      approaches require repeated delivery of bacteria and large numbers of animals and
      vary in treatment start time. A method is needed that can shift the microbiota of
      predisposed individuals to a healthy microbiota at an early age and sustain this
      shift through the lifetime of the individual. RESULTS: We tested cross-fostering
      of pups within 48 h of birth as a means to permanently shift the microbiota from
      birth. Taxonomical analysis revealed that the nursing mother was the critical
      factor in determining bacterial colonization, instead of the birth mother. Data
      was evaluated using bacterial 16S rDNA sequences from fecal pellets and
      sequencing was performed on an Illumina Miseq using a 251 bp paired-end library.
      CONCLUSIONS: The results show that cross-fostering is an effective means to
      induce an early and maintained shift in the commensal microbiota. This will allow
      for the evaluation of a prolonged microbial shift and its effects on disease
      pathogenesis. Cross-fostering will also eliminate variation within control models
      by normalizing the commensal microbiota between different strains of mice.

PMID- 25969736
TI  - Deriving accurate microbiota profiles from human samples with low bacterial
      content through post-sequencing processing of Illumina MiSeq data.
AB  - BACKGROUND: The rapid expansion of 16S rRNA gene sequencing in challenging
      clinical contexts has resulted in a growing body of literature of variable
      quality. To a large extent, this is due to a failure to address spurious signal
      that is characteristic of samples with low levels of bacteria and high levels of
      non-bacterial DNA. We have developed a workflow based on the paired-end read
      Illumina MiSeq-based approach, which enables significant improvement in data
      quality, post-sequencing. We demonstrate the efficacy of this methodology through
      its application to paediatric upper-respiratory samples from several anatomical
      sites. RESULTS: A workflow for processing sequence data was developed based on
      commonly available tools. Data generated from different sample types showed a
      marked variation in levels of non-bacterial signal and 'contaminant' bacterial
      reads. Significant differences in the ability of reference databases to
      accurately assign identity to operational taxonomic units (OTU) were observed.
      Three OTU-picking strategies were trialled as follows: de novo, open-reference
      and closed-reference, with open-reference performing substantially better.
      Relative abundance of OTUs identified as potential reagent contamination showed a
      strong inverse correlation with amplicon concentration allowing their objective
      removal. The removal of the spurious signal showed the greatest improvement in
      sample types typically containing low levels of bacteria and high levels of human
      DNA. A substantial impact of pre-filtering data and spurious signal removal was
      demonstrated by principal coordinate and co-occurrence analysis. For example,
      analysis of taxon co-occurrence in adenoid swab and middle ear fluid samples
      indicated that failure to remove the spurious signal resulted in the inclusion of
      six out of eleven bacterial genera that accounted for 80% of similarity between
      the sample types. CONCLUSIONS: The application of the presented workflow to a set
      of challenging clinical samples demonstrates its utility in removing the spurious
      signal from the dataset, allowing clinical insight to be derived from what would
      otherwise be highly misleading output. While other approaches could potentially
      achieve similar improvements, the methodology employed here represents an
      accessible means to exclude the signal from contamination and other artefacts.

PMID- 25969738
TI  - A rare case showing subacute thyroiditis-like symptoms with amyloid goiter after
      anti-tumor necrosis factor therapy.
AB  - Anti-tumor necrosis factor (TNF)-alpha therapy is established as a new standard
      for the treatment of various autoimmune inflammatory diseases. We report the
      first case showing subacute thyroiditis-like symptoms with an amyloid goiter
      after anti-TNF-alpha therapy. A 56-year-old man with Crohn's disease presented
      with fever and a diffuse, tender goiter. To control the diarrhea, anti-TNF
      therapy (infliximab) was administered 4 weeks before the thyroid symptoms
      emerged. The patient reported a swollen neck with tenderness on the right side
      and fever 4 days after the second infliximab injection. An elevated serum C
      reactive protein (CRP) and serum thyroid hormone level with suppressed serum
      thyrotropin were observed. The thyroid-stimulating antibody was not elevated. An
      ultrasonograph of the thyroid revealed an enlarged goiter with posterior
      echogenicity attenuation and a low echoic region that was tender. The thyroid
      uptake value on technetium-99m scintigraphy was near the lower limit of the
      normal range. The patient was initially diagnosed with thyrotoxicosis resulting
      from subacute thyroiditis. Administration of oral prednisolone improved the
      fever, thyroid pain, and thyroid function, but his thyroid remained swollen. The
      patient developed diarrhea after prednisolone withdrawal; therefore, adalimumab,
      another TNF inhibitor, was administered. After three injections, his abdominal
      symptoms were alleviated, but the thyroid pain and fever recurred. Elevated serum
      CRP levels in the absence of thyroid dysfunction were observed. The patient's
      symptoms resolved after prednisolone retreatment, but an elastic, firm goiter
      persisted. A fine-needle biopsy revealed amyloid deposition in the thyroid.
      LEARNING POINTS: Many cases with thyroid dysfunction accompanied by amyloid
      goiter have been reported.There are cases that develop amyloid goiter with
      subacute thyroiditis-like symptoms after anti-TNF therapy.When the thyroid
      remains swollen after improvement of thyrotoxicosis following treatment with
      prednisolone, it should be assessed to differentiate between an amyloid goiter
      and common subacute thyroiditis.

PMID- 25969737
TI  - Forensic analysis of the microbiome of phones and shoes.
AB  - BACKGROUND: Microbial interaction between human-associated objects and the
      environments we inhabit may have forensic implications, and the extent to which
      microbes are shared between individuals inhabiting the same space may be relevant
      to human health and disease transmission. In this study, two participants sampled
      the front and back of their cell phones, four different locations on the soles of
      their shoes, and the floor beneath them every waking hour over a 2-day period. A
      further 89 participants took individual samples of their shoes and phones at
      three different scientific conferences. RESULTS: Samples taken from different
      surface types maintained significantly different microbial community structures.
      The impact of the floor microbial community on that of the shoe environments was
      strong and immediate, as evidenced by Procrustes analysis of shoe replicates and
      significant correlation between shoe and floor samples taken at the same time
      point. Supervised learning was highly effective at determining which participant
      had taken a given shoe or phone sample, and a Bayesian method was able to
      determine which participant had taken each shoe sample based entirely on its
      similarity to the floor samples. Both shoe and phone samples taken by conference
      participants clustered into distinct groups based on location, though much more
      so when an unweighted distance metric was used, suggesting sharing of low
      abundance microbial taxa between individuals inhabiting the same space.
      CONCLUSIONS: Correlations between microbial community sources and sinks allow for
      inference of the interactions between humans and their environment.

PMID- 25969739
TI  - The effects of exergaming on balance, gait, technology acceptance and flow
      experience in people with multiple sclerosis: a randomized controlled trial.
AB  - BACKGROUND: Exergaming is a promising new alternative to traditional modes of
      therapeutic exercise which may be preferable and more effective for people with
      Multiple Sclerosis (MS). Impaired balance is reported as one of the most
      disabling aspects of MS. The purposes of this study were to examine the effects
      of exergaming on: (1) postural sway, (2) gait, (3) technology acceptance and (4)
      flow experience in people with MS. Secondary outcomes were disability: 12-item
      Multiple Sclerosis Walking Scale (MSWS-12) and the World Health Organization
      Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire. METHODS: Fifty-six
      adults (mean age = 52 years, SD = 5.8; 38 women) with a clinical diagnosis of MS
      and able to walk 100 meters with or without use of a walking aid were included in
      this study and randomized into 3 groups. Group 1 received balance training using
      the Nintendo Wii FitTM (exergaming) and Group 2 undertook traditional balance
      training (non-exergaming). Group 3 acted as a control group, receiving no
      intervention. Exergaming and traditional balance training groups received four
      weeks of twice weekly balance-orientated exercise. Postural sway was measured
      using a KistlerTM force platform. Spatiotemporal parameters of gait were measured
      using a GAITRiteTM computerised walkway. Technology acceptance and flow
      experience were measured using the Unified Theory of Acceptance and Use of
      Technology and the Flow State Scale questionnaires, respectively. RESULTS: There
      were significant improvements in bipedal postural sway in both intervention
      groups when compared to the control group; and no effects of either intervention
      on gait. There were no significant differences between the interventions in
      technology acceptance but on several dimensions of flow experience the Wii FitTM
      was superior to traditional balance training. Both interventions showed
      improvements in disability compared to control. CONCLUSIONS: In terms of the
      physical effects of exergaming, the Wii FitTM is comparable to traditional
      balance training. These findings would support the use of the Wii FitTM as an
      effective means of balance and gait training for people with MS, which is both
      accepted and intrinsically motivating to MS users. TRIAL REGISTRATION: Controlled
      Trials ISRCTN13924231.

PMID- 25969740
TI  - Implementing a structured education program for children with diabetes: lessons
      learnt from an integrated process evaluation.
AB  - BACKGROUND: There is recognition of an urgent need for clinic-based interventions
      for young people with type 1 diabetes mellitus that improve glycemic control and
      quality of life. The Child and Adolescent Structured Competencies Approach to
      Diabetes Education (CASCADE) is a structured educational group program, using
      psychological techniques, delivered primarily by diabetes nurses. Composed of
      four modules, it is designed for children with poor diabetic control and their
      parents. A mixed methods process evaluation, embedded within a cluster randomized
      control trial, aimed to assess the feasibility, acceptability, fidelity, and
      perceived impact of CASCADE. METHODS: 28 pediatric diabetes clinics across
      England participated and 362 children aged 8-16 years, with type 1 diabetes and a
      mean glycosylated hemoglobin (HbA1c) of 8.5 or above, took part. The process
      evaluation used a wide range of research methods. RESULTS: Of the 180 families in
      the intervention group, only 55 (30%) received the full program with 53%
      attending at least one module. Only 68% of possible groups were run. Staff found
      organizing the groups burdensome in terms of arranging suitable dates/times and
      satisfactory group composition. Some staff also reported difficulties in
      mastering the psychological techniques. Uptake, by families, was influenced by
      the number of groups run and by school, work and other commitments. Attendees
      described improved: family relationships; knowledge and understanding;
      confidence; motivation to manage the disease. The results of the trial showed
      that the intervention did not significantly improve HbA1c at 12 or 24 months.
      CONCLUSIONS: Clinic-based structured group education delivered by staff using
      psychological techniques had perceived benefits for parents and young people.
      Staff and families considered it a valuable intervention, yet uptake was poor and
      the burden on staff was high. Recommendations are made to inform issues related
      to organization, design, and delivery in order to potentially enhance the impact
      of CASCADE and future programs. CURRENT CONTROLLED TRIALS: ISRCTN52537669.

PMID- 25969741
TI  - Initiation of human regular U-500 insulin use is associated with improved
      glycemic control: a real-world US cohort study.
AB  - AIM: Describe the characteristics of patients initiating human regular U-500
      insulin (U-500R) and their subsequent glycemic control in a real-world setting.
      METHODS: US Humedica electronic health record system data (July 2007-September
      2011) were used to identify patients with diabetes aged >=18 years with >=1
      records for U-500R prescriptions, 6 months of preindex data, 12 months following
      first use of U-500R, and at least one glycated hemoglobin (HbA1c) value in both
      preindex and postindex periods. Paired t tests were used to measure the change in
      HbA1c from preindex to postindex periods (last or most recent values) and
      hypoglycemia. RESULTS: Among patients initiating U-500R (N=445), 96.9% had type 2
      diabetes with mean age 57 years and mean body mass index 40.4 kg/m(2). Postindex
      prescriptions were written for U-500R alone (47.0%, group A) and concomitant U
      500R/U-100 insulins (53.0%, group B). Concomitant oral antihyperglycemic agents
      (AHAs) and non-insulin injectable AHAs were used by 43.4% and 14.6% of patients,
      respectively. Following initiation of U-500R, mean HbA1c improved 0.68% in all
      patients (p<0.0001 compared with baseline), but the decrease in HbA1c did not
      differ significantly between groups (A: 0.78%; B: 0.60%). Overall, hypoglycemic
      events, largely captured in the outpatient setting, increased in incidence from
      6.7% to 11.9% (p<=0.0001) and from 0.23 to 0.39 events/patient/year, an increase
      of 0.16 (p=0.003), from preindex to postindex. CONCLUSIONS: This real-world
      outcomes analysis demonstrates that U-500R initiation is associated with a
      clinically meaningful improvement in glycemic control over the subsequent 12
      month period with modest increase in incidence and rate of hypoglycemia.

PMID- 25969742
TI  - Sex differences in the association of fasting and postchallenge glucose levels
      with grip strength among older adults: the Rancho Bernardo Study.
AB  - OBJECTIVE: Persons with diabetes have accelerated muscle loss. The association of
      fasting and postchallenge glucose levels per se to grip strength, a clinical
      marker of poor physical function, and potential sex differences in this
      relationship has not been previously described. DESIGN: Longitudinal cohort.
      SETTING: USA. PARTICIPANTS: Participants were community-dwelling older adults
      (mean age 71.3 years) without self-reported diabetes and/or use of diabetes
      medication with glucose measured at baseline (1992-1996). MEASUREMENTS: Fasting
      plasma glucose (FPG) was measured in 1019 women and 636 men. Two-hour glucose
      (2HG) levels after a 75 g oral glucose tolerance test were also available (women,
      n=870; men, n=559). Dominant hand grip strength was assessed using a hand-held
      dynamometer at 3.0+/-1.6 visits over a median 7.0 years. Mixed linear models
      examined the association of baseline glucose levels with grip strength,
      accounting for repeated visits, and adjusting for covariates. RESULTS: Sex
      specific FPG quartiles were associated with unadjusted differences in grip
      strength among women (p=0.03) but not men (p=0.50). However, in men, adjusting
      for age, education, height, weight, peripheral neuropathy, physical activity, and
      comorbidities, each SD (SD=17 mg/dL) higher FPG was associated with persistently
      lower grip strength (-0.44+/-0.22 kg, p=0.049); 2HG (SD=50 mg/dL) was unrelated
      to grip strength (-0.39+/-0.25 kg, p=0.13). In women, neither FPG (SD=16 mg/dL)
      nor 2HG (SD=45 mg/dL) was associated with grip strength (0.02+/-0.12 kg, p=0.90;
      and -0.20+/-0.14 kg, p=0.14; respectively) after adjustment. The rate of change
      in grip strength did not differ across FPG or 2HG quartiles in either sex.
      CONCLUSIONS: In age-adjusted analyses, elevated fasting glucose levels are
      associated with persistently lower grip strength in older men, but not women.
      Future studies are needed to elucidate reasons for these sex differences and may
      provide further insight into accelerated loss of muscle function as a
      complication of diabetes in older adults.

PMID- 25969743
TI  - Bio301: A Web-Based EST Annotation Pipeline That Facilitates Functional
      Comparison Studies.
AB  - In this postgenomic era, a huge volume of information derived from expressed
      sequence tags (ESTs) has been constructed for functional description of gene
      expression profiles. Comparative studies have become more and more important to
      researchers of biology. In order to facilitate these comparative studies, we have
      constructed a user-friendly EST annotation pipeline with comparison tools on an
      integrated EST service website, Bio301. Bio301 includes regular EST
      preprocessing, BLAST similarity search, gene ontology (GO) annotation, statistics
      reporting, a graphical GO browsing interface, and microarray probe selection
      tools. In addition, Bio301 is equipped with statistical library comparison
      functions using multiple EST libraries based on GO annotations for mining
      meaningful biological information. 

PMID- 25969744
TI  - Signal Peptidase Complex Subunit 1 and Hydroxyacyl-CoA Dehydrogenase Beta Subunit
      Are Suitable Reference Genes in Human Lungs.
AB  - Lung cancer is a common cancer, and expression profiling can provide an accurate
      indication to advance the medical intervention. However, this requires the
      availability of stably expressed genes as reference. Recent studies had shown
      that genes that are stably expressed in a tissue may not be stably expressed in
      other tissues suggesting the need to identify stably expressed genes in each
      tissue for use as reference genes. DNA microarray analysis has been used to
      identify those reference genes with low fluctuation. Fourteen datasets with
      different lung conditions were employed in our study. Coefficient of variance,
      followed by NormFinder, was used to identify stably expressed genes. Our results
      showed that classical reference genes such as GAPDH and HPRT1 were highly
      variable; thus, they are unsuitable as reference genes. Signal peptidase complex
      subunit 1 (SPCS1) and hydroxyacyl-CoA dehydrogenase beta subunit (HADHB), which
      are involved in fundamental biochemical processes, demonstrated high expression
      stability suggesting their suitability in human lung cell profiling. 

PMID- 25969745
TI  - Construction of a drug safety assurance information system based on clinical
      genotyping.
AB  - To capitalize on the vast potential of patient genetic information to aid in
      assuring drug safety, a substantial effort is needed in both the training of
      healthcare professionals and the operational enablement of clinical environments.
      Our research aims to satisfy these needs through the development of a drug safety
      assurance information system (GeneScription) based on clinical genotyping that
      utilizes patient-specific genetic information to predict and prevent adverse drug
      responses. In this paper, we present the motivations for this work, the
      algorithms at the heart of GeneScription, and a discussion of our system and its
      uses. We also describe our efforts to validate GeneScription through its
      evaluation by practicing pharmacists and pharmacy professors and its repeated use
      in training pharmacists. The positive assessment of the GeneScription software
      tool by these domain experts provides strong validation of the importance,
      accuracy, and effectiveness of GeneScription. 

PMID- 25969746
TI  - Classifying multigraph models of secondary RNA structure using graph-theoretic
      descriptors.
AB  - The prediction of secondary RNA folds from primary sequences continues to be an
      important area of research given the significance of RNA molecules in biological
      processes such as gene regulation. To facilitate this effort, graph models of
      secondary structure have been developed to quantify and thereby characterize the
      topological properties of the secondary folds. In this work we utilize a
      multigraph representation of a secondary RNA structure to examine the ability of
      the existing graph-theoretic descriptors to classify all possible topologies as
      either RNA-like or not RNA-like. We use more than one hundred descriptors and
      several different machine learning approaches, including nearest neighbor
      algorithms, one-class classifiers, and several clustering techniques. We predict
      that many more topologies will be identified as those representing RNA secondary
      structures than currently predicted in the RAG (RNA-As-Graphs) database. The
      results also suggest which descriptors and which algorithms are more informative
      in classifying and exploring secondary RNA structures. 

PMID- 25969747
TI  - A Systolic Array-Based FPGA Parallel Architecture for the BLAST Algorithm.
AB  - A design of systolic array-based Field Programmable Gate Array (FPGA) parallel
      architecture for Basic Local Alignment Search Tool (BLAST) Algorithm is proposed.
      BLAST is a heuristic biological sequence alignment algorithm which has been used
      by bioinformatics experts. In contrast to other designs that detect at most one
      hit in one-clock-cycle, our design applies a Multiple Hits Detection Module which
      is a pipelining systolic array to search multiple hits in a single-clock-cycle.
      Further, we designed a Hits Combination Block which combines overlapping hits
      from systolic array into one hit. These implementations completed the first and
      second step of BLAST architecture and achieved significant speedup comparing with
      previously published architectures. 

PMID- 25969748
TI  - A robust topology-based algorithm for gene expression profiling.
AB  - Early and accurate diagnoses of cancer can significantly improve the design of
      personalized therapy and enhance the success of therapeutic interventions.
      Histopathological approaches, which rely on microscopic examinations of malignant
      tissue, are not conducive to timely diagnoses. High throughput genomics offers a
      possible new classification of cancer subtypes. Unfortunately, most clustering
      algorithms have not been proven sufficiently robust. We propose a novel approach
      that relies on the use of statistical invariants and persistent homology, one of
      the most exciting recent developments in topology. It identifies a sufficient but
      compact set of genes for the analysis as well as a core group of tightly
      correlated patient samples for each subtype. Partitioning occurs hierarchically
      and allows for the identification of genetically similar subtypes. We analyzed
      the gene expression profiles of 202 tumors of the brain cancer glioblastoma
      multiforme (GBM) given at the Cancer Genome Atlas (TCGA) site. We identify core
      patient groups associated with the classical, mesenchymal, and proneural subtypes
      of GBM. In our analysis, the neural subtype consists of several small groups
      rather than a single component. A subtype prediction model is introduced which
      partitions tumors in a manner consistent with clustering algorithms but requires
      the genetic signature of only 59 genes. 

PMID- 25969749
TI  - Hybrid-controlled neurofuzzy networks analysis resulting in genetic regulatory
      networks reconstruction.
AB  - Reverse engineering of gene regulatory networks (GRNs) is the process of
      estimating genetic interactions of a cellular system from gene expression data.
      In this paper, we propose a novel hybrid systematic algorithm based on neurofuzzy
      network for reconstructing GRNs from observational gene expression data when only
      a medium-small number of measurements are available. The approach uses fuzzy
      logic to transform gene expression values into qualitative descriptors that can
      be evaluated by using a set of defined rules. The algorithm uses neurofuzzy
      network to model genes effects on other genes followed by four stages of decision
      making to extract gene interactions. One of the main features of the proposed
      algorithm is that an optimal number of fuzzy rules can be easily and rapidly
      extracted without overparameterizing. Data analysis and simulation are conducted
      on microarray expression profiles of S. cerevisiae cell cycle and demonstrate
      that the proposed algorithm not only selects the patterns of the time series gene
      expression data accurately, but also provides models with better reconstruction
      accuracy when compared with four published algorithms: DBNs, VBEM, time delay
      ARACNE, and PF subjected to LASSO. The accuracy of the proposed approach is
      evaluated in terms of recall and F-score for the network reconstruction task. 

PMID- 25969750
TI  - Dynamic clustering of gene expression.
AB  - It is well accepted that genes are simultaneously involved in multiple biological
      processes and that genes are coordinated over the duration of such events.
      Unfortunately, clustering methodologies that group genes for the purpose of novel
      gene discovery fail to acknowledge the dynamic nature of biological processes and
      provide static clusters, even when the expression of genes is assessed across
      time or developmental stages. By taking advantage of techniques and theories from
      time frequency analysis, periodic gene expression profiles are dynamically
      clustered based on the assumption that different spectral frequencies
      characterize different biological processes. A two-step cluster validation
      approach is proposed to statistically estimate both the optimal number of
      clusters and to distinguish significant clusters from noise. The resulting
      clusters reveal coordinated coexpressed genes. This novel dynamic clustering
      approach has broad applicability to a vast range of sequential data scenarios
      where the order of the series is of interest. 

PMID- 25969751
TI  - Electric LAMP: Virtual Loop-Mediated Isothermal AMPlification.
AB  - We present eLAMP, a PERL script, with Tk graphical interface, that electronically
      simulates Loop-mediated AMPlification (LAMP) allowing users to efficiently test
      putative LAMP primers on a set of target sequences. eLAMP can match primers to
      templates using either exact (via builtin PERL regular expressions) or
      approximate matching (via the tre-agrep library). Performance was tested on 40
      whole genome sequences of Staphylococcus. eLAMP correctly predicted that the two
      tested primer sets would amplify from S. aureus genomes and not amplify from
      other Staphylococcus species. Open source (GNU Public License) PERL scripts are
      available for download from the New York Botanical Garden's website. 

PMID- 25969752
TI  - Enhancing de novo transcriptome assembly by incorporating multiple overlap sizes.
AB  - Background. The emergence of next-generation sequencing platform gives rise to a
      new generation of assembly algorithms. Compared with the Sanger sequencing data,
      the next-generation sequence data present shorter reads, higher coverage depth,
      and different error profiles. These features bring new challenging issues for de
      novo transcriptome assembly. Methodology. To explore the influence of these
      features on assembly algorithms, we studied the relationship between read overlap
      size, coverage depth, and error rate using simulated data. According to the
      relationship, we propose a de novo transcriptome assembly procedure, called Euler
      mix, and demonstrate its performance on a real transcriptome dataset of mice. The
      simulation tool and evaluation tool are freely available as open source.
      Significance. Euler-mix is a straightforward pipeline; it focuses on dealing with
      the variation of coverage depth of short reads dataset. The experiment result
      showed that Euler-mix improves the performance of de novo transcriptome assembly.

PMID- 25969753
TI  - HMEC: A Heuristic Algorithm for Individual Haplotyping with Minimum Error
      Correction.
AB  - Haplotype is a pattern of single nucleotide polymorphisms (SNPs) on a single
      chromosome. Constructing a pair of haplotypes from aligned and overlapping but
      intermixed and erroneous fragments of the chromosomal sequences is a nontrivial
      problem. Minimum error correction approach aims to minimize the number of errors
      to be corrected so that the pair of haplotypes can be constructed through
      consensus of the fragments. We give a heuristic algorithm (HMEC) that searches
      through alternative solutions using a gain measure and stops whenever no better
      solution can be achieved. Time complexity of each iteration is O(m (3) k) for an
      m * k SNP matrix where m and k are the number of fragments (number of rows) and
      number of SNP sites (number of columns), respectively, in an SNP matrix.
      Alternative gain measure is also given to reduce running time. We have compared
      our algorithm with other methods in terms of accuracy and running time on both
      simulated and real data, and our extensive experimental results indicate the
      superiority of our algorithm over others. 

PMID- 25969755
TI  - Characterization of LlaKI, a New Metal Ion-Independent Restriction Endonuclease
      from Lactococcus lactis KLDS4.
AB  - Requirement of divalent cations for DNA cleavage is a general feature of type II
      restriction enzymes with the exception of few members of this group. A new type
      II restriction endonuclease has been partially purified from Lactococcus lactis
      KLDS4. The enzyme was denoted as LlaKI and showed to recognize and cleave the
      same site as FokI. The enzyme displayed a denatured molecular weight of 50 kDa
      and behaved as a dimer in solution as evidenced by the size exclusion
      chromatography. To investigate the role of divalent cations in DNA cleavage by
      LlaKI, digestion reactions were carried out at different Mg(2+), Mn(2+), and
      Ca(2+) concentrations. Unlike most of type II restriction endonucleases, LlaKI
      did not require divalent metal ions to cleave DNA and is one of the few metal
      independent restriction endonucleases found in bacteria. The enzyme showed near
      maximal levels of activity in 10 mM Tris-HCl pH 7.9, 50 mM NaCl, 10 mM MgCl2, and
      1 mM dithiothreitol at 30 degrees C. The presence of DNA modification was also
      determined and was correlated with the correspondent restriction enzyme. 

PMID- 25969756
TI  - Feeding of Bait to Snail Lymnaea acuminata and Their Effect on Certain Enzyme in
      the Nervous Tissue.
AB  - Fascioliasis, a snail-borne parasitic zoonosis, has been recognized for a long
      time because of its major veterinary and human impact. Different Bait
      formulations were fed to the snail Lymnaea acuminata in clear glass aquaria
      having diameter of 30 cm. Snail attractant containing bait formulations was
      prepared from different binary combination (1 : 1 ratio) of carbohydrates
      (glucose, starch 10 mM) and amino acid (methionine, histidine 10 mM) in 100 ml of
      2% agar solution + sublethal (20% and 60% of 24 h and 96 h LC50) doses of
      different molluscicides (eugenol, ferulic acid, umbelliferone, and limonene).
      Snails fed on bait containing sub-lethal concentration of different molluscicides
      and the snail attractant, causing a significant inhibition in alkaline
      phosphatase (ALP) and acetylcholinesterase (AChE) activity in the nervous tissue
      of the vector snail L. acuminata. Maximum inhibition in ALP (20% of control) and
      AChE (49.49% of control) activity was observed in the nervous tissue of the L.
      acuminata exposed to 60% of 96 h LC50 of eugenol in the bait pellets containing
      starch + histidine, starch + methionine, respectively. 

PMID- 25969754
TI  - Neuronal nicotinic receptors in sleep-related epilepsy: studies in integrative
      biology.
AB  - Although Mendelian diseases are rare, when considered one by one, overall they
      constitute a significant social burden. Besides the medical aspects, they propose
      us one of the most general biological problems. Given the simplest physiological
      perturbation of an organism, that is, a single gene mutation, how do its effects
      percolate through the hierarchical biological levels to determine the
      pathogenesis? And how robust is the physiological system to this perturbation? To
      solve these problems, the study of genetic epilepsies caused by mutant ion
      channels presents special advantages, as it can exploit the full range of modern
      experimental methods. These allow to extend the functional analysis from single
      channels to whole brains. An instructive example is autosomal dominant nocturnal
      frontal lobe epilepsy (ADNFLE), which can be caused by mutations in neuronal
      nicotinic acetylcholine receptors. In vitro, such mutations often produce
      hyperfunctional receptors, at least in heterozygous condition. However,
      understanding how this leads to sleep-related frontal epilepsy is all but
      straightforward. Several available animal models are helping us to determine the
      effects of ADNFLE mutations on the mammalian brain. Because of the complexity of
      the cholinergic regulation in both developing and mature brains, several
      pathogenic mechanisms are possible, which also present different therapeutic
      implications. 

PMID- 25969758
TI  - Constrained peptides as miniature protein structures.
AB  - This paper discusses the recent developments of protein engineering using both
      covalent and noncovalent bonds to constrain peptides, forcing them into designed
      protein secondary structures. These constrained peptides subsequently can be used
      as peptidomimetics for biological functions such as regulations of protein
      protein interactions. 

PMID- 25969759
TI  - Withaferin a induces proteasome-dependent degradation of breast cancer
      susceptibility gene 1 and heat shock factor 1 proteins in breast cancer cells.
AB  - The purpose of this study was to examine the regulation of prosurvival factors
      heat shock factor 1 (HSF1) and breast cancer susceptibility gene 1 (BRCA1) by a
      natural withanolide withaferin A (WA) in triple negative breast cancer cell lines
      MDA-MB-231 and BT20. Western analysis was used to examine alternations in HSF1
      and BRCA1 protein levels following WA treatment. A protein synthesis inhibitor
      cycloheximide and a proteasome inhibitor MG132 were used to investigate the
      mechanisms of HSF1 and BRCA1 regulation by WA. It was found that WA induced a
      dose-dependent decrease in HSF1 and BRCA1 protein levels. Further analysis showed
      that levels of HSF1 and BRCA1 proteins decreased rapidly after WA treatment, and
      this was attributed to WA-induced denaturation of HSF1 and BRCA1 proteins and
      subsequent degradation via proteasome-dependent, and protein-synthesis dependent
      mechanism. In summary, WA induces denaturation and proteasomal degradation of
      HSF1 and BRCA1 proteins. Further studies are warranted to examine the
      contribution of HSF1 and BRCA1 depletion to the anticancer effects of WA in
      breast cancer. 

PMID- 25969761
TI  - The effect of the combined action of roscovitine and Paclitaxel on the apoptotic
      and cell cycle regulatory mechanisms in colon and anaplastic thyroid cancer
      cells.
AB  - Aim. To study the significance of cyclin-dependent kinases (Cdks) in paclitaxel
      dependent apoptosis in colon and undifferentiated thyroid cancer cells. Materials
      and Methods. Experiments were performed on undifferentiated thyroid carcinoma
      (KTC-2) and colon carcinoma (ARO) cell lines. Cells were treated with paclitaxel
      (Ptx) and inhibitor of Cdk, roscovitine. Cell survival test and Western blotting
      were used for characterization of the effects of paclitaxel and roscovitine on
      cancer cells. Results. It was shown that not c-Jun N-terminal kinase, but cyclin
      dependent kinases are responsible for antiapoptotic Bcl-2 phosphorylation. Cdk
      inhibition enhanced the cytotoxic effects of Ptx at low drug concentrations.
      There was antagonism between Ptx and roscovitine at higher (25 nM) paclitaxel
      concentrations. Conclusion. Using of paclitaxel at low (2.5 to 5 nM)
      concentrations and roscovitine is a promising combination for further preclinical
      trials for the development of new therapeutic approaches to the treatment of
      colon and anaplastic thyroid cancer. 

PMID- 25969762
TI  - Role of Elicitors in Inducing Resistance in Plants against Pathogen Infection: A
      Review.
AB  - Disease control is largely based on the use of fungicides, bactericides, and
      insecticides-chemical compounds toxic to plant invaders, causative agents, or
      vectors of plant diseases. However, the hazardous effect of these chemicals or
      their degradation products on the environment and human health strongly
      necessitates the search for new, harmless means of disease control. There must be
      some natural phenomenon of induced resistance to protect plants from disease.
      Elicitors are compounds, which activate chemical defense in plants. Various
      biosynthetic pathways are activated in treated plants depending on the compound
      used. Commonly tested chemical elicitors are salicylic acid, methyl salicylate,
      benzothiadiazole, benzoic acid, chitosan, and so forth which affect production of
      phenolic compounds and activation of various defense-related enzymes in plants.
      Their introduction into agricultural practice could minimize the scope of
      chemical control, thus contributing to the development of sustainable
      agriculture. This paper chiefly highlights the uses of elicitors aiming to draw
      sufficient attention of researchers to the frontier research needed in this
      context. 

PMID- 25969763
TI  - Locus-specific biochemical epigenetics/chromatin biochemistry by insertional
      chromatin immunoprecipitation.
AB  - Comprehensive understanding of regulation mechanisms of biological phenomena
      mediated by functions of genomic DNA requires identification of molecules bound
      to genomic regions of interest in vivo. However, nonbiased methods to identify
      molecules bound to specific genomic loci in vivo are limited. To perform
      biochemical and molecular biological analysis of specific genomic regions, we
      developed the insertional chromatin immunoprecipitation (iChIP) technology to
      purify the genomic regions of interest. We applied iChIP to direct identification
      of components of insulator complexes, which function as boundaries of chromatin
      domain, showing that it is feasible to directly identify proteins and RNA bound
      to a specific genomic region in vivo by using iChIP. In addition, recently, we
      succeeded in identifying proteins and genomic regions interacting with a single
      copy endogenous locus. In this paper, we will discuss the application of iChIP to
      epigenetics and chromatin research. 

PMID- 25969760
TI  - Calpain dysregulation in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by the presence of senile plaques and
      neurofibrillary tangles in the neocortex and hippocampus of AD patients. In
      addition, a marked decrease in synaptic contacts has been detected in these
      affected brain areas. Due to its prevalence in the aging population, this disease
      has been the focus of numerous studies. The data obtained from those studies
      suggest that the mechanisms leading to the formation of the hallmark lesions of
      AD might be linked. One of such mechanisms seems to be the dysregulation of
      calcium homeostasis that results in the abnormal activation of calpains. Calpains
      are a family of Ca(2+)-dependent cysteine proteases that play a key role in
      multiple cell functions including cell development, differentiation and
      proliferation, axonal guidance, growth cone motility, and cell death, among
      others. In this paper, we briefly reviewed data on the structure of these
      proteases and their regulation under normal conditions. We also summarized data
      underscoring the participation of calpains in the neurodegenerative mechanisms
      associated with AD. 

PMID- 25969764
TI  - Kinetic Characterization and Effect of Immobilized Thermostable beta-Glucosidase
      in Alginate Gel Beads on Sugarcane Juice.
AB  - A thermostable beta-glucosidase was effectively immobilized on alginate by the
      method of gel entrapment. After optimization of immobilized conditions, recovered
      enzyme activity was 60%. Optimum pH, temperature, kinetic parameters, thermal and
      pH stability, reusability, and storage stability were investigated. The K m and V
      max for immobilized beta-glucosidase were estimated to be 5.0 mM and 0.64 U/ml,
      respectively. When comparing, free and immobilized enzyme, change was observed in
      optimum pH and temperature from 5.0 to 6.0 and 60 degrees C to 80 degrees C,
      respectively. Immobilized enzyme showed an increase in pH stability over the
      studied pH range (3.0-10.0) and stability at temperature up to 80 degrees C. The
      storage stability and reusability of the immobilized beta-glucosidase were
      improved significantly, with 12.09% activity retention at 30 degrees C after
      being stored for 25 d and 17.85% residual activity after being repeatedly used
      for 4 times. The effect of both free and immobilized beta-glucosidase enzyme on
      physicochemical properties of sugarcane juice was also analyzed. 

PMID- 25969765
TI  - Analysis of mathematical modelling on potentiometric biosensors.
AB  - A mathematical model of potentiometric enzyme electrodes for a nonsteady
      condition has been developed. The model is based on the system of two coupled
      nonlinear time-dependent reaction diffusion equations for Michaelis-Menten
      formalism that describes the concentrations of substrate and product within the
      enzymatic layer. Analytical expressions for the concentration of substrate and
      product and the corresponding flux response have been derived for all values of
      parameters using the new homotopy perturbation method. Furthermore, the complex
      inversion formula is employed in this work to solve the boundary value problem.
      The analytical solutions obtained allow a full description of the response curves
      for only two kinetic parameters (unsaturation/saturation parameter and
      reaction/diffusion parameter). Theoretical descriptions are given for the two
      limiting cases (zero and first order kinetics) and relatively simple approaches
      for general cases are presented. All the analytical results are compared with
      simulation results using Scilab/Matlab program. The numerical results agree with
      the appropriate theories. 

PMID- 25969757
TI  - Ganglioside biochemistry.
AB  - Gangliosides are sialic acid-containing glycosphingolipids. They occur especially
      on the cellular surfaces of neuronal cells, where they form a complex pattern,
      but are also found in many other cell types. The paper provides a general
      overview on their structures, occurrence, and metabolism. Key functional,
      biochemical, and pathobiochemical aspects are summarized. 

PMID- 25969766
TI  - Association of MRS-Based Vertebral Bone Marrow Fat Fraction with Bone Strength in
      a Human In Vitro Model.
AB  - Bone marrow adiposity has recently gained attention due to its association with
      bone loss pathophysiology. In this study, ten vertebrae were harvested from fresh
      human cadavers. Trabecular BMD and microstructure parameters were extracted from
      MDCT. Bone marrow fat fractions were determined using single-voxel MRS. Failure
      load (FL) values were assessed by destructive biomechanical testing. Significant
      correlations (P < 0.05) were observed between MRS-based fat fraction and MDCT
      based parameters (up to r = -0.72) and MRS-based fat fraction and FL (r = -0.77).
      These findings underline the importance of the bone marrow in the pathophysiology
      and imaging diagnostics of osteoporosis. 

PMID- 25969767
TI  - Ethanol and Volatile Fatty Acid Production from Lignocellulose by Clostridium
      cellulolyticum.
AB  - Clostridium cellulolyticum is capable of producing glycosyl hydrolase enzymes as
      well as fermentation products including ethanol and acetate. In this study, the
      potential of using C. cellulolyticum for ethanol and volatile fatty acid
      production from straw and grape pomace was examined. For rice straw, the effects
      of alkaline pretreatment and substrate sterilization prior to fermentation on
      products yields were also investigated. Effects of alkaline pretreatment and
      necessity for subsequent washing were tested for two types of grape pomace. For
      rice straw, the highest ethanol yield was 0.16 g/gVS from the straw pretreated
      with 10% sodium hydroxide loading at 121 degrees C for 1 hour. Sterilization of
      the straw prior to fermentation was found to be not significant for ethanol
      production. Sterilization appeared to decrease native acetogen populations in the
      rice straw, resulting in lower acetic acid yields. The highest ethanol yield from
      grape pomace was of 0.09 g/gVS from the pretreated pomace. Pomace type (red or
      white) and washing were found to be not significant. Ethanol yields by C.
      cellulolyticum were lower than those from yeast in a simultaneous
      saccharification and fermentation system, but overall conversion of cellulose and
      hemicellulose was high, between 68 and 79%. 

PMID- 25969768
TI  - Antimicrobial Pressure of Ciprofloxacin and Gentamicin on Biofilm Development by
      an Endoscope-Isolated Pseudomonas aeruginosa.
AB  - This work aims at characterizing endoscope biofilm-isolated (PAI) and reference
      strain P. aeruginosa (PA) adhesion, biofilm formation and sensitivity to
      antibiotics. The recovery ability of the biofilm-growing bacteria subjected to
      intermittent antibiotic pressure (ciprofloxacin (CIP) and gentamicin (GM)), as
      well as the development of resistance towards antibiotics and benzalkonium
      chloride (BC), were also determined. The capacity of both strains to develop
      biofilms was greatly impaired in the presence of CIP and GM. Sanitization was not
      complete allowing biofilm recovery after the intermittent cycles of antibiotic
      pressure. The environmental pressure exerted by CIP and GM did not develop P.
      aeruginosa resistance to antibiotics nor cross-resistance towards BC. However,
      data highlighted that none of the antimicrobials led to complete biofilm
      eradication, allowing the recovery of the remaining adhered population possibly
      due to the selection of persister cells. This feature may lead to biofilm
      recalcitrance, reinforcement of bacterial attachment, and recolonization of other
      sites. 

PMID- 25969769
TI  - Linen most useful: perspectives on structure, chemistry, and enzymes for retting
      flax.
AB  - The components of flax (Linum usitatissimum) stems are described and illustrated,
      with reference to the anatomy and chemical makeup and to applications in
      processing and products. Bast fiber, which is a major economic product of flax
      along with linseed and linseed oil, is described with particular reference to its
      application in textiles, composites, and specialty papers. A short history of
      retting methods, which is the separation of bast fiber from nonfiber components,
      is presented with emphasis on water retting, field retting (dew retting), and
      experimental methods. Past research on enzyme retting, particularly by the use of
      pectinases as a potential replacement for the current commercial practice of
      field retting, is reviewed. The importance and mechanism of Ca(2+) chelators with
      pectinases in retting are described. Protocols are provided for retting of both
      fiber-type and linseed-type flax stems with different types of pectinases.
      Current and future applications are listed for use of a wide array of enzymes to
      improve processed fibers and blended yarns. Finally, potential lipid and aromatic
      coproducts derived from the dust and shive waste streams of fiber processing are
      indicated. 

PMID- 25969770
TI  - Development of biological oxygen demand biosensor for monitoring the fermentation
      industry effluent.
AB  - A biosensor was developed for the determination of BOD value of fermentation
      industry effluent. The developed biosensor was fabricated by immobilizing the
      microbial consortium on cellulose acetate (CA) membrane in close proximity to a
      DO probe electrode. The microbial consortium was harvested from the fermentation
      industry effluent. The BOD biosensor was calibrated by using a solution
      containing the equivalent amount of glucose/glutamic acid (GGA) as a standard
      sample solution. The response time was optimized by immobilizing different
      concentrations of cell biomass on CA membrane. Once the response time was
      optimized, it was used for determination of BOD of fermentation industry
      effluent. For analysis of fermentation industry effluent, the response time was
      observed 7 minutes with detection limit 1 mg/L. Good linear range with GGA
      standard solution was observed, R (2) 0.99 with relative standard deviation (RSD)
      <%. The observed BOD value by biosensor showed a good comparison with the
      conventional method for the determination of BOD. 

PMID- 25969771
TI  - Simultaneous Extraction Optimization and Analysis of Flavonoids from the Flowers
      of Tabernaemontana heyneana by High Performance Liquid Chromatography Coupled to
      Diode Array Detector and Electron Spray Ionization/Mass Spectrometry.
AB  - Flavonoids are exploited as antioxidants, antimicrobial, antithrombogenic,
      antiviral, and antihypercholesterolemic agents. Normally, conventional extraction
      techniques like soxhlet or shake flask methods provide low yield of flavonoids
      with structural loss, and thereby, these techniques may be considered as
      inefficient. In this regard, an attempt was made to optimize the flavonoid
      extraction using orthogonal design of experiment and subsequent structural
      elucidation by high-performance liquid chromatography-diode array detector
      electron spray ionization/mass spectrometry (HPLC-DAD-ESI/MS) techniques. The
      shake flask method of flavonoid extraction was observed to provide a yield of 1.2
      +/- 0.13 (mg/g tissue). With the two different solvents, namely, ethanol and
      ethyl acetate, tried for the extraction optimization of flavonoid, ethanol (80.1
      mg/g tissue) has been proved better than ethyl acetate (20.5 mg/g tissue). The
      optimal conditions of the extraction of flavonoid were found to be 85 degrees C,
      3 hours with a material ratio of 1 : 20, 75% ethanol, and 1 cycle of extraction.
      About seven different phenolics like robinin, quercetin, rutin, sinapoyl
      hexoside, dicaffeic acid, and two unknown compounds were identified for the first
      time in the flowers of T. heyneana. The study has also concluded that L16
      orthogonal design of experiment is an effective method for the extraction of
      flavonoid than the shake flask method. 

PMID- 25969772
TI  - A Convenient RP-HPLC Method for Assay Bioactivities of Angiotensin I-Converting
      Enzyme Inhibitory Peptides.
AB  - A convenient and accurate reversed-phase high-performance liquid chromatography
      (RP-HPLC) method for angiotensin I-converting enzyme inhibitory peptides assay
      was described in this paper. The mobile phase consisted of 70% A (0.05% TFA and
      0.05% triethylamine in water, pH = 2.9-3.3) and 30% B (100% acetonitrile) using
      an Isogradient program. The flow rate was 0.5 mL/min. The absorb wavelength was
      226.5 nm; the column temperature was controlled at 25 degrees C. This method for
      angiotensin I-converting enzyme inhibitory peptides assay was convenient for the
      Iso-gradient program. The accuracy of the RT-HPLC method was verified by
      analyzing ACE inhibitory activity of the hydrolysate peptides of silkworm pupae
      protein, and the results showed that the RT-HPLC method was available for
      exploring new source of angiotensin I-converting enzyme inhibitory peptides
      rapidly and veraciously. 

PMID- 25969773
TI  - Biosynthesis of Gold Nanoparticles Using Fusarium oxysporum f. sp. cubense JT1, a
      Plant Pathogenic Fungus.
AB  - The development of reliable processes for the synthesis of gold nanoparticles is
      an important aspect of current nanotechnology research. Recently, reports are
      published on the extracellular as well as intracellular biosynthesis of gold
      nanoparticles using microorganisms. However, these methods of synthesis are
      rather slow. In present study, rapid and extracellular synthesis of gold
      nanoparticles using a plant pathogenic fungus F. oxysporum f. sp. cubense JT1
      (FocJT1) is reported. Incubation of FocJT1 mycelium with auric chloride solution
      produces gold nanoparticles in 60 min. Gold nanoparticles were characterized by
      UV-Vis spectroscopy, FTIR, and particle size analysis. The particles synthesized
      were of 22 nm sized, capped by proteins, and posed antimicrobial activity against
      Pseudomonas sp. 

PMID- 25969774
TI  - Enzyme-enhanced extraction of phenolic compounds and proteins from flaxseed meal.
AB  - Flaxseed (Linum usitatissimum) meal, the main byproduct of the flaxseed oil
      extraction process, is composed mainly of proteins, mucilage, and phenolic
      compounds. The extraction methods of phenolics either commonly employed the use
      of mixed solvents (dioxane/ethanol, water/acetone, water/methanol, and
      water/ethanol) or are done with the aid of alkaline, acid, or enzymatic
      hydrolysis. This work aimed at the study of optimal conditions for a clean
      process, using renewable solvents and enzymes, for the extraction of phenolics
      and proteins from flaxseed meal. After a screening of the most promising
      commercial preparations based on different carbohydrases and proteases, a central
      composite rotatable design and a mixture design were applied, achieving as
      optimal results a solution containing 6.6 and 152 g kg(-1) meal of phenolics and
      proteins, respectively. The statistical approach used in the present study for
      the enzyme-enhanced extraction of phenolics and proteins from the major flaxseed
      byproduct was effective. By means of the sequential experimental design
      methodology, the extraction of such compounds was increased 10-fold and 14-fold,
      when compared to a conventional nonenzymatic extraction. 

PMID- 25969775
TI  - The Use of Response Surface Methodology as a Statistical Tool for Media
      Optimization in Lipase Production from the Dairy Effluent Isolate Fusarium
      solani.
AB  - The optimization of extracellular lipase production by Fusarium isolani strain
      SKWF7 isolated from dairy wastewater was carried out in this study. Initially,
      the physicochemical factors significantly influencing enzyme production were
      studied by varying one-factor-at-a-time (OFAT). A mesophilic temperature of 40
      degrees C, alkaline pH of 8, and incubation period of 72 hours were found to be
      the optimal conditions for lipase production. Among the media components, the
      disaccharide sucrose acted as the best carbon source; palm oil as the best
      inducing lipid substrate; casein and (NH4)2SO4 as the best organic and inorganic
      nitrogen sources; Ca(2+) ion as the best trace element. In the next phase of
      work, statistical optimization of medium components was performed by employing
      the Box-Behnken design of Response Surface Methodology (RSM). The optimum
      concentrations of three significant factors, namely, palm oil, (NH4)2SO4, and
      CaCO3 were determined by this method to be 5% (v/v), 5.5 g/L, and 0.1 g/L,
      respectively. RSM-guided design of experiments resulted in a maximum lipase
      production of 73.3 U/ml, which is a 1.7-fold increase in comparison with that
      obtained in the unoptimized medium. These results point towards the success of
      the model in developing a process for the production of lipase, an enzyme of
      enormous industrial significance. 

PMID- 25969776
TI  - Critical Factors Affecting the Success of Cloning, Expression, and Mass
      Production of Enzymes by Recombinant E. coli.
AB  - E. coli is the most frequently used host for production of enzymes and other
      proteins by recombinant DNA technology. E. coli is preferable for its relative
      simplicity, inexpensive and fast high-density cultivation, well-known genetics,
      and large number of compatible molecular tools available. Despite all these
      advantages, expression and production of recombinant enzymes are not always
      successful and often result in insoluble and nonfunctional proteins. There are
      many factors that affect the success of cloning, expression, and mass production
      of enzymes by recombinant E. coli. In this paper, these critical factors and
      approaches to overcome these obstacles are summarized focusing controlled
      expression of target protein/enzyme in an unmodified form at industrial level. 

PMID- 25969777
TI  - Induction of Defense-Related Enzymes in Banana Plants: Effect of Live and Dead
      Pathogenic Strain of Fusarium oxysporum f. sp. cubense.
AB  - The aim of the present study was to scrutinize the response of banana (Grand
      Naine variety) plants when interacting with dead or live pathogen, Fusarium
      oxysporum f.sp. cubense, a causative agent of Panama disease. Response of plants
      was evaluated in terms of induction of defense-related marker enzyme activity,
      namely, peroxidase (POX), polyphenol oxidase (PPO), beta-1,3 glucanase,
      chitinase, and phenolics. Plant's interaction with live pathogen resulted in
      early induction of defense to restrain penetration as well as antimicrobial
      productions. However, pathogen overcame the defense of plant and caused disease.
      Interaction with dead pathogen resulted in escalating defense response in plants.
      Later on plants inoculated with dead pathogen showed resistance to even forced
      inoculation of live pathogen. Results obtained in the present study suggest that
      dead pathogen was able to mount defense response in plants and provide resistance
      to Panama disease upon subsequent exposure. Therefore, preparation from dead
      pathogen could be a potential candidate as a biocontrol agent or plant vaccine to
      combat Panama disease. 

PMID- 25969779
TI  - Effect of Potassium Ions on Protoplast Generation during Yeast Induction from
      Mucor circinelloides Tieghem.
AB  - Mucor circinelloides aerobically exhibits coenocytic thallic growth habit with
      straight and circinate sporangiophores which culminate in globose or pyriform
      columellae enclosed within sporangial walls. It undergoes dimorphic switch with
      its conversion to multipolar budding yeast-like cells or thallic conidia. This
      paper confirms the induction of plurality of reproductive structures of the
      pleomorphic microorganism in minimal medium. Furthermore, construction of pH
      differentials at inflection points in the biphasic profiles during sporangiospore
      yeast transformation indicated the intensity of H(+) release from intracellular
      medium of the growing microorganism in a study conducted with K(+) levels (0.0,
      0.5, 0.7, 0.9, 1.0,1.10 g/L)-mediated broths. Optimum proton release was at 0.00
      and 1.0 g/L K(+)-supplemented broths, but specific growth rate was least in the
      latter. It also coincided with a preponderance of neoplastic units, protoplasts,
      and terminal budding yeast cells. On either side of this K(+) level, variation in
      morphologies, including neoplasts, protoplasts, septate hyphae, thallic,
      holothallic, and holoblastic conidia, was greater, although olive-green septate
      hyphae with vesicular conidiogenous apparatus occurred at all K(+) levels tested.
      This study suggested that following the establishment of transmembrane pH
      gradient across protoplast membrane, operation of Mitchellian proton pump was
      further promoted, thus leading to active transport mechanism, a prelude to yeast
      morphology induction. 

PMID- 25969778
TI  - Occurrence of Biosurfactant Producing Bacillus spp. in Diverse Habitats.
AB  - Diversity among biosurfactant producing Bacillus spp. from diverse habitats was
      studied among 77 isolates. Cluster analysis based on phenotypic characteristics
      using unweighted pair-group method with arithmetic averages (UPGMAs) method was
      performed. Bacillus isolates possessing high surface tension activity and five
      reference strains were subjected to amplified 16S rDNA restriction analysis
      (ARDRA). A correlation between the phenotypic and genotypic characterization of
      Bacillus spp. is explored. Most of the oil reservoir isolates showing high
      surface activity clustered with B. licheniformis and B. subtilis, the hot water
      spring isolates clustered in two ingroups, while the petroleum contaminated soil
      isolates were randomly distributed in all the three ingroups. Present work
      revealed that diversity exists in distribution of Bacillus spp. from thermal and
      hydrocarbon containing habitats where majority of organisms belonged to B.
      licheniformis and B. subtilis group. Isolate B. licheniformis TT42 produced
      biosurfactant which reduced the surface tension of water from 72 mNm(-1) to 28
      mNm(-1), and 0.05 mNm(-1) interfacial tension against crude oil at 80 degrees C.
      This isolate clustered with B. subtilis and B. licheniformis group on the basis
      of ARDRA. These findings increase the possibility of exploiting the Bacillus spp.
      from different habitats and their possible use in oil recovery. 

PMID- 25969780
TI  - Macromolecular Crowding Enhances Catalytic Efficiency and Stability of alpha
      Amylase.
AB  - In the present study an attempt was made to investigate the macromolecular
      crowding effect on functional attributes of alpha-amylase. High concentrations of
      sugar based cosolvents, (e.g., trehalose, sucrose, sorbitol, and glycerol) were
      used to mimic the macromolecular crowding environment (of cellular milieu) under
      in vitro conditions. To assess the effect of macromolecular crowding, the
      activity and structural properties of the enzyme were evaluated in the presence
      of different concentrations of the above cosolvents. Based on the results it is
      suggested that the macromolecular crowding significantly improves the catalytic
      efficiency of the enzyme with marginal change in the structure. Out of four
      cosolvents examined, trehalose was found to be the most effective in consistently
      enhancing thermal stability of the enzyme. Moreover, the relative effectiveness
      of the above cosolvents was found to be dependent on their concentration used. 

PMID- 25969781
TI  - Properties and Application of a Partially Purified Thermoalkali Stable Xylanase
      from Cellulosimicrobium sp. MTCC 10645 in Kraft Pulp Bleaching.
AB  - The most promising application of xylanases (E.C. 3.2.1.8) is in the prebleaching
      of kraft pulp. The present paper reports bleaching effects of a thermoalkali
      stable xylanase from Cellulosimicrobium sp. MTCC 10645. The bacterium produced
      thermo-alkali stable xylanase in a basal medium supplemented with wheat bran (1%
      w/v), which was optimally active at pH 7.0 and 50 degrees C. The xylanase was
      stable at temperature 50 degrees C for 1 h and retained up to 86% of the
      activity. The xylanase was stable in a broad pH range of 6.0-11.0 for 1 h at 50
      degrees C. Metal ions Ca(+2), Hg(+2), and Pb(+2) were inhibitory for xylanase
      retaining 72.3%, 35.07% and 36.7% relative activity at 10 mM concentration,
      whereas Fe(+2), Cu(+2), Mn(+2), Na(+2), Co(+2), and Zn(+2) were inducers at
      concentrations of 5 mM and 10 mM. The enzyme exhibited greater binding affinity
      exclusively for xylans but not for avicel, CMC, cellobiose, starch, or p
      nitrophenyl xylopyranoside. Parachloromercuric benzoate and iodoacetamide were
      found stimulatory, while potassium permanganate, cysteine, and cystine markedly
      reduced the activity. The xylanase dose of 2.0 U/g dry weight pulp of 10%
      consistency gave optimum bleach boosting of kraft pulp at pH 8.0 and temperature
      50 degrees C for 5 h reaction time. 

PMID- 25969782
TI  - Global stability of predator-prey system with alternative prey.
AB  - A predator-prey model in presence of alternative prey is proposed. Existence and
      local stability conditions for interior equilibrium points are derived. Global
      stability conditions for interior equilibrium points are also found. Bifurcation
      analysis is done with respect to predator's searching rate and handling time.
      Bifurcation analysis confirms the existence of global stability in presence of
      alternative prey. 

PMID- 25969783
TI  - Challenges in enzymatic route of mannitol production.
AB  - Mannitol is an important biochemical often used as medicine and in food sector,
      yet its biotechnological is not preffered in Industry for large scale production,
      which may be due to the multistep mechanism involved in hydrogenation and
      reduction. This paper is a comparative preview covering present chemical and
      biotechnological approaches existing today for mannitol production at industrial
      scale. Biotechnological routes are suitable for adaptation at industrial level
      for mannitol production, and whatever concerns are there had been discussed in
      detail, namely, raw materials, broad range of enzymes with high activity at
      elevated temperature suitable for use in reactor, cofactor limitation, reduced by
      product formation, end product inhibition, and reduced utilization of mannitol
      for enhancing the yield with maximum volumetric productivity. 

PMID- 25969784
TI  - Effect of extruder screw speed, temperature, and enzyme levels on sugar recovery
      from different biomasses.
AB  - Biofuels from biomass have the potential to reduce the dependency on fossil
      fuels. An efficient pretreatment method is required to accomplish the target of
      the Energy Act 2005. Extrusion could be a viable continuous pretreatment method
      to be explored. The objectives of the current study were to investigate the
      influence of screw speed and barrel temperature on sugar recovery from the
      selected warm season grasses and to select a suitable enzyme combination and dose
      for enzymatic hydrolysis. The ground, moisture-balanced biomasses were pretreated
      using a single screw extruder at various screw speeds (100, 150, and 200 rpm) and
      barrel temperatures (50, 75, 100, 150, and 200 degrees C). Cellulase or
      multienzyme with beta-glucosidase was varied from 1 : 1 to 1 : 4 during enzymatic
      hydrolysis to accomplish the second objective. Screw speed, barrel temperature,
      and their interaction had a significant influence on sugar recovery from the
      selected biomasses. A maximum of 28.2, 66.2, and 49.2% of combined sugar
      recoverywasachieved for switchgrass, big bluestem, prairie cord grass when
      pretreated at a screw speed of 200, 200, and 150 rpm and at a barrel temperature
      of 75, 150, and 100 degrees C, respectively, using cellulase and beta-glucosidase
      at a ratio of 1 :  4. Extrusion pretreatment of these biomasses used only 28-37%
      of the rated extruder power. 

PMID- 25969785
TI  - Temperature Effect on Morphobiochemical Characters in Some Black Gram (Vigna
      mungo) Genotypes.
AB  - Lack of suitable varieties and genotypes of black gram with adaptation to local
      conditions is among the factors affecting its production. Efforts to genetically
      improve the crop mostly involve identifying important morphological descriptors
      followed by development of advanced breeding lines for locale-specific cultivars.
      The present day available black gram varieties have not been properly
      characterized for their thermo sensitiveness with respect to morphological and
      biochemical characters. Hence efforts were taken in the present research to study
      the effect of the temperature on these characters in seven black gram varieties
      over different development stages. We aimed at studying the effect of 3
      temperature regimes for identifying suitable stress tolerant genotypes. High
      percent germination (87.2%), root length (3.68 cm), carbohydrate content (3.72 mg
      g(-1) fresh tissue) among the genotypes was highest at 10 degrees C-20 degrees C
      temperature. High shoot length (13.39 cm), free amino acid content (3.73 mg g(-1)
      fresh tissue), and protein content (9.54 mg g(-1) fresh tissue) was found to be
      present when the genotypes were exposed to 20 degrees C-30 degrees C temperature.
      The black gram varieties J.L and PDU-1 performed best in all the temperature
      regimes over characters. Thus suitable varieties for all temperature regimes were
      identified using biochemical analysis. 

PMID- 25969786
TI  - Better rooting procedure to enhance survival rate of field grown malaysian
      eksotika papaya transformed with 1-aminocyclopropane-1-carboxylic Acid oxidase
      gene.
AB  - A high survival rate for transformed papaya plants when transferred to the field
      is useful in the quest for improving the commercial quality traits. We report in
      this paper an improved rooting method for the production of transformed Malaysian
      Eksotika papaya with high survival rate when transferred to the field. Shoots
      were regenerated from embryogenic calli transformed with antisense and RNAi
      constructs of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes using the
      Agrobacterium tumefaciens-mediated transformation method. Regenerated transformed
      shoots, each measuring approximately 3-4 cm in height, were cultured in liquid
      half-strength Murashige and Skoog (MS) medium or sterile distilled water, and
      with either perlite or vermiculite supplementation. All the culturing processes
      were conducted either under sterile or nonsterile condition. The results showed
      that rooting under sterile condition was better. Shoots cultured in half-strength
      MS medium supplemented with vermiculite exhibited a 92.5% rooting efficiency
      while perlite showed 77.5%. The survival rate of the vermiculite-grown
      transformed papaya plantlets after transfer into soil, contained in polybags, was
      94%, and the rate after transfer into the ground was 92%. Morpho-histological
      analyses revealed that the tap roots were more compact, which might have
      contributed to the high survival rates of the plantlets. 

PMID- 25969787
TI  - Elimination of bisphenol a and triclosan using the enzymatic system of
      autochthonous colombian forest fungi.
AB  - Bisphenol A (BPA) and triclosan (TCS) are known or suspected potential endocrine
      disrupting chemicals (EDCs) which may pose a risk to human health and have an
      environmental impact. Enzyme preparations containing mainly laccases, obtained
      from Ganoderma stipitatum and Lentinus swartzii, two autochthonous Colombian
      forest white rot fungi (WRF), previously identified as high enzyme producers,
      were used to remove BPA and TCS from aqueous solutions. A Box-Behnken factorial
      design showed that pH, temperature, and duration of treatment were significant
      model terms for the elimination of BPA and TCS. Our results demonstrated that
      these EDCs were extensively removed from 5 mg L(-1) solutions after a contact
      time of 6 hours. Ninety-four percent of TCS and 97.8% of BPA were removed with
      the enzyme solution from G. stipitatum; 83.2% of TCS and 88.2% of BPA were
      removed with the L. swartzii enzyme solution. After a 6-hour treatment with
      enzymes from G. stipitatum and L. swartzii, up to 90% of the estrogenic activity
      of BPA was lost, as shown by the yeast estrogen screen assay. 2,2-Azino-bis-(3
      ethylthiazoline-6-sulfonate) (ABTS) was used as a mediator (laccase/mediator
      system) and significantly improved the laccase catalyzed elimination of BPA and
      TCS. The elimination of BPA in the absence of a mediator resulted in production
      of oligomers of molecular weights of 454, 680, and 906 amu as determined by mass
      spectra analysis. The elimination of TCS in the same conditions produced dimers,
      trimers, and tetramers of molecular weights of 574, 859, and 1146 amu.
      Ecotoxicological studies using Daphnia pulex to determine lethal concentration
      (LC50) showed an important reduction of the toxicity of BPA and TCS solutions
      after enzymatic treatments. Use of laccases emerges thus as a key alternative in
      the development of innovative wastewater treatment technologies. Moreover, the
      exploitation of local biodiversity appears as a potentially promising approach
      for identifying new efficient strains for biotechnological applications. 

PMID- 25969788
TI  - Comparison of Lipase Production by Enterococcus faecium MTCC 5695 and Pediococcus
      acidilactici MTCC 11361 Using Fish Waste as Substrate: Optimization of Culture
      Conditions by Response Surface Methodology.
AB  - A medium using fish waste as substrate was designed for production of lipase by
      Enterococcus faecium MTCC 5695 and Pediococcus acidilactici MTCC 11361. Medium
      components and culture conditions (fish waste protein hydrolysate (FWPH)
      concentration, fish waste oil (FWO) concentration, pH, temperature, and
      fermentation time) which affect lipase production were screened using factorial
      (5 factors * 2 levels) design of which FWPH concentration, FWO concentration, and
      fermentation time showed significance (P < 0.05). The levels of these factors
      were optimized further by Box-Behnken design using response surface methodology
      (RSM). Optimized conditions were found to be 5% v/v FWO, 0.15 mg/mL FWPH and 24 h
      of fermentation time for MTCC 5695, and 4% v/v FWO, 0.15 mg/mL FWPH and 24 h of
      fermentation for MTCC 11361, which were further validated. Under optimized
      conditions, MTCC 5695 and MTCC 11361 showed 3.15- (543.63 to 1715 U/mL) and 2.3-
      (214.74 to 493 U/mL) fold increase in lipase production, respectively, as
      compared to unoptimized conditions. 

PMID- 25969789
TI  - Kinetic study of Acid hydrolysis of rice straw.
AB  - Rice straw is a renewable, cheap, and abundant waste in tropical countries. The
      pentose content of rice straw can be used as a substrate for many types of value
      added products such as xylitol and biofuel. Dilute acid hydrolysis mainly
      releases pentose from rice straw. The objective of the study was to determine the
      effect of H2SO4 concentration and reaction time on the xylose production. The
      variation of the main product xylose with the reaction time was described by a
      kinetic model and kinetic parameters were calculated to describe the variation of
      the xylose production with time. The optimum yield (19.35 g/L) was obtained at
      0.24 mol/L H2SO4 and 30 minutes. 

PMID- 25969790
TI  - Thermostable Alkaline Phytase from Alcaligenes sp. in Improving Bioavailability
      of Phosphorus in Animal Feed: In Vitro Analysis.
AB  - A bacterial isolate, Alcaligenes sp. secreting phytase (EC 3.1.3.8), was isolated
      and characterized. The optimum conditions for the production of phytase included
      a fermentation period of 96 h, pH 8.0, and the addition of 1% (w/v) maltose and
      1% (w/v) beef extract to the culture medium. This enzyme was purified to
      homogeneity and had an apparent molecular mass of 41 kDa. The optimum pH range
      and temperature for the activity of phytase were found to be 7.0-8.0 and 60
      degrees C, respectively. This enzyme was strongly inhibited by 0.005 M of Mn(2+),
      Mg(2+), and Zn(2+). In vitro studies revealed that the phytase from Alcaligenes
      sp. released inorganic phosphate from plant phytates. Phytase released 1930 +/-
      28, 1740 +/- 13, 1050 +/- 31, 845 +/- 7, 1935 +/- 32, and 1655 +/- 21 mg
      inorganic phosphate/kg plant phytates, namely, chick pea, corn, green pea,
      groundnut, pearl pea, and chick feed, respectively. 

PMID- 25969791
TI  - Glioblastoma and intracranial aneurysms: Case report and review of literature.
AB  - BACKGROUND: There is a paucity of data on the association of glioblastoma
      multiforme (GBM) with intracranial aneurysms. It is an important clinical entity
      for physicians to be aware of and its presence illustrates several critical
      features of the pathophysiology of malignant glioma. In this article we present a
      case of a middle cerebral artery (MCA) pseudoaneurysm that occurred in a patient
      with recurrent GBM as well discuss the current literature relating to this unique
      combination of pathologies. CASE DESCRIPTION: The authors present a case of a MCA
      pseudoaneurysm that developed in a patient with recurrent GBM and discuss the
      current literature. The authors identified 19 reports describing 23 patients
      harboring both GBM and an intracranial aneurysm. CONCLUSION: Several theories
      stand to explain the coincidental occurrence of intracranial aneurysms and GBM.
      The treating physician should be aware of this association when patients with
      intraaxial tumors present with unusual manifestation such as an intratumoral
      hemorrhage or angiogram negative subarachnoid hemorrhage. No guidelines exist to
      assist in the management of such patients; therefore, authors have attempted to
      address this issue using a classification and treatment algorithm.

PMID- 25969792
TI  - Thrombosis of posterior condylar vein with extension to internal jugular vein; a
      rare radiological finding in traumatic brain injury.

PMID- 25969793
TI  - Distance reporting in digital pathology: A study on 950 cases.
AB  - BACKGROUND: Increased workload, case complexity, financial constraints, and
      staffing shortages justify wider implementations of digital pathology. One of its
      main advantages is distance reporting. AIM: A feasibility study was conducted at
      our institution in order to achieve comprehensive pathology services available by
      distance. METHODS: One senior pathologist reported 950 cases (3,650 slides) by
      distance during 19 weeks. Slides were scanned by ScanScope AT Turbo (Aperio) and
      digital images accessed through SymPathy (Tieto) on a 14" laptop. Mobile phone,
      mobile broadband, broadband over Wi-Fi and broadband were used for internet
      connections along with a virtual private network technology (VPN). Lync
      (Microsoft) was tested for one case consultation and resident's teaching session.
      Larger displays were accessed when available. Effects of ergonomics and working
      flexibility on the user experience were observed. Details on network speed,
      frequency of technical issues, data usage, scanning, and turnaround, were
      collected and evaluated. Turnaround was compared to in-office microscopic
      reporting, measured from the registration to sign off. RESULTS: Network speeds
      varied 1-80 Mbps (median download speed 8-65 Mbps). 20 Mbps were satisfactory for
      the instant upload of digital images. VPN, image viewer, and laptop failed on two
      occasions each. An estimated data usage per digital image was 10 MB (1-50 MB).
      Two cases (15 slides) were deferred to microscopic slides (0.21/0.41%) due to
      scanty material and suboptimal slide quality. Additional nine cases (15 slides)
      needed to be rescanned for various reasons (0.95/0.41%). Average turnaround was
      shorter, and the percentage of cases reported up to 3 days higher (3.13
      days/72.25%) comparing with in-office microscopic reporting (3.90 days/40.56%).
      Larger displays improved the most user experience at magnifications over *20.
      CONCLUSIONS: Existing IT solutions at our institution allow efficient and
      reliable distance reporting for the core pathology services in histology and
      cytology. Stable network speeds, fully integrated laboratory information
      management system, technical reliability, working flexibility, larger displays,
      and shorter turnaround contributed to the overall satisfaction with distance
      reporting. A further expansion of our pathology services available by distance,
      diagnostic and educational, rely on gaining experience in digital reporting and
      marginal IT investment. Adjustments to the organization of pathology services may
      follow to fully benefit from the implementation of digital pathology.

PMID- 25969794
TI  - Contributors and Inhibitors of Resilience Among Adolescents and Young Adults with
      Cancer.
AB  - Purpose: Self-perceived resilience may enable coping and mitigate poor
      psychosocial outcomes among adolescent and young adult (AYA) patients with
      cancer. In order to inform the development of resilience-promoting interventions,
      we aimed to: (1) describe AYA patient-reported resilience and (2) identify AYA
      patient-reported contributors and inhibitors of resilience. Methods: The
      "Resilience in Adolescents and Young Adults with Cancer" study was a prospective
      longitudinal mixed-methods study. Consecutive Caucasian patients aged 14-25 years
      old enrolled 14-60 days following their diagnosis of cancer and completed one-on
      one semi-structured interviews both at the time of enrollment and 3-6 months
      later. Constant comparative analyses identified salient themes describing
      modifiable contributors and inhibitors to patient-perceived resilience. Results:
      Seventeen patients (85% of those approached) enrolled in the study. The mean age
      was 17 years (SD=2.6) and 53% were female. All patient definitions of resilience
      inferred an ability to handle adversity. Five themes emerged as predominant
      contributors or inhibitors of resilience: (1) stress and coping; (2) goals,
      purpose, and planning; (3) optimism; (4) gratitude and meaning; and (5)
      connection and belonging. Merged analyses suggested that AYA resilience was a
      balance that may be enabled by promoting certain skills. Conclusion: AYA patients
      with cancer perceive resilience as a balance. Learned skills in stress
      management, goal-setting, and benefit-finding may empower AYAs during their
      cancer experience, in turn improving long-term psychosocial outcomes.

PMID- 25969795
TI  - A systematic review of the health impacts of mass Earth movements (landslides).
AB  - Background. Mass ground movements (commonly referred to as 'landslides') are
      common natural hazards that can have significant economic, social and health
      impacts. They occur as single events, or as clusters, and are often part of
      'disaster' chains, occurring secondary to, or acting as the precursor of other
      disaster events. Whilst there is a large body of literature on the engineering
      and geological aspects of landslides, the mortality and morbidity caused by
      landslides is less well documented. As far as we are aware, this is the first
      systematic review to examine the health impacts of landslides. Methods. The
      MEDLINE, EMBASE, CINAHL, SCOPUS databases and the Cochrane library were
      systematically searched to identify articles which considered the health impacts
      of landslides. Case studies, case series, primary research and systematic reviews
      were included. News reports, editorials and non-systematic reviews were excluded.
      Only articles in English were considered. The references of retrieved papers were
      searched to identify additional articles. Findings. 913 abstracts were reviewed
      and 143 full text articles selected for review. A total of 27 papers reporting
      research studies were included in the review (25 from initial search, 1 from
      review of references and 1 from personal correspondence). We found a limited
      number of studies on the physical health consequences of landslides. Only one
      study provided detail of the causes of mortality and morbidity in relation a
      landslide event. Landslides cause significant mental health impacts, in
      particular the prevalence of PTSD may be higher after landslides than other types
      of disaster, though these studies tend to be older with only 3 papers published
      in the last 5 years, with 2 being published 20 years ago, and diagnostic criteria
      have changed since they were produced. Discussion. We were disappointed at the
      small number of relevant studies, and the generally poor documentation of the
      health impacts of landslides. Mental health impacts were better documented,
      though some of the studies are now quite old. Further research on the health
      impacts of landslides needs to be undertaken to support those responding to
      landslide disasters and to aid disaster risk mitigation advocacy. 

PMID- 25969796
TI  - Revitalising Evidence-based Policy for the Sendai Framework for Disaster Risk
      Reduction 2015-2030: Lessons from Existing International Science Partnerships.
AB  - The convergence of agreements on disaster risk reduction (DRR), development
      finance, sustainable development and climate change in 2015 presents a unique
      opportunity for coherence across these inter-related policy areas. At the same
      time, demand is growing for a more prominent and effective role for science and
      technology in providing evidence for policy, with the international community
      recognising that successful disaster risk reduction (DRR) depends on it.
      Reflecting this ambition, science is included as a core aspect of the Sendai
      Framework for Disaster Risk Reduction 2015-2030, although the ways in which this
      will be implemented in practice is still unclear. This paper aims to inform the
      implementation of international science coordination for DRR by examining a
      number of existing international science partnerships used across other relevant
      areas of policy to understand best practice, options for coordination and lessons
      identified. In the field of DRR, the science-policy interface needs to be
      strengthened in line with the best practice described in this review. An enhanced
      UNISDR Scientific and Technical Advisory Group will be given the mandate for to
      enhance the evidence base for DRR and mobilise science and technical work in
      coordination with a broad range of stakeholders. The structure and function of an
      enhanced STAG must be as open, as inclusive and as participatory as possible in
      order to build trust in new and existing institutions at local, national,
      regional and global levels. The challenge for the international community is to
      facilitate evidence-based policy making by formally recognising the links between
      DRR, development finance, sustainable development and climate change in the
      upcoming post-2015 agreements. 

PMID- 25969799
TI  - Sol-gel microspheres doped with glycerol: a structural insight in light of
      forthcoming applications in the polyurethane foam industry.
AB  - Invited for this months cover are the groups of Professor Mario Pagliaro at the
      Istituto per lo Studio dei Materiali Nanostrutturati in Palermo and Professor
      Laura Ilharco at the Instituto Superior Tecnico in Lisboa. The cover picture
      shows a- GreenCaps- microcapsule breaking and releasing encapsulated glycerol
      after the organosilica microspheres are sprayed from a pressurized polyurethane
      foam can. This shows how glycerol acts as a solid curing agent, promoting
      crosslinking of partially polymerized diphenylmethane diisocyanate. For more
      details, see the Full Paper on p. 120 ff. 

PMID- 25969800
TI  - Graphical Abstract: ChemistryOpen 2/2015.

PMID- 25969797
TI  - Understanding the emergence of ebola virus disease in sierra leone: stalking the
      virus in the threatening wake of emergence.
AB  - Since Ebola Virus Disease (EVD) was first identified in 1976 in what is now the
      Democratic Republic of Congo, and despite the numerous outbreaks recorded to
      date, rarely has an epidemic origin been identified. Indeed, among the twenty-one
      most documented EVD outbreaks in Africa, an index case has been identified four
      times, and hypothesized in only two other instances. The initial steps of
      emergence and spread of a virus are critical in the development of a potential
      outbreak and need to be thoroughly dissected and understood in order to improve
      on preventative strategies. In the current West African outbreak of EVD, a unique
      index case has been identified, pinpointing the geographical origin of the
      epidemic in Guinea. Herein, we provide an accounting of events that serve as the
      footprint of EVD emergence in Sierra Leone and a road map for risk mitigation
      fueled by lessons learned. 

PMID- 25969802
TI  - Spotlights on our sister journals: ChemistryOpen 2/2015.

PMID- 25969803
TI  - Development of a wavelength-shifting fluorescent module for the adenosine aptamer
      using photostable cyanine dyes.
AB  - DNA-based aptamers are commonly used recognition elements in biosensors for a
      range of target molecules. Here, the development of a wavelength-shifting optical
      module for a DNA-based adenosine-binding aptamer is described. It applies the
      combination of two photostable cyanine-styryl dyes as covalent modifications.
      This energy-transfer pair is postsynthetically attached to oligonucleotides via a
      copper(I)-catalyzed azide-alkyne cycloaddition by two structurally different
      approaches: 1) as nucleotide modifications at the 2'-position of uridines and 2)
      as nucleotide substitutions using (S)-amino-1,2-propanediol as acyclic linker
      between the phosphodiester bridges. Both dyes exhibit a remarkable
      photostability. A library of DNA aptamers consisting of different combinations of
      the two dyes in diagonal orientations were evaluated by their emission color
      contrast as readout. Further optimization led to aptasensors with improved
      fluorescent readout as compared with previously reported aptasensors. This
      approach described is synthetically facile using simple propargylated
      phosphoramidites as DNA building blocks. As such, this approach could be applied
      for other dyes and other chemical/biological applications. 

PMID- 25969804
TI  - Regulating the coordination state of a heme protein by a designed distal hydrogen
      bonding network.
AB  - Heme coordination state determines the functional diversity of heme proteins.
      Using myoglobin as a model protein, we designed a distal hydrogen-bonding network
      by introducing both distal glutamic acid (Glu29) and histidine (His43) residues
      and regulated the heme into a bis-His coordination state with native ligands
      His64 and His93. This resembles the heme site in natural bis-His coordinated heme
      proteins such as cytoglobin and neuroglobin. A single mutation of L29E or F43H
      was found to form a distinct hydrogen-bonding network involving distal water
      molecules, instead of the bis-His heme coordination, which highlights the
      importance of the combination of multiple hydrogen-bonding interactions to
      regulate the heme coordination state. Kinetic studies further revealed that
      direct coordination of distal His64 to the heme iron negatively regulates
      fluoride binding and hydrogen peroxide activation by competing with the exogenous
      ligands. The new approach developed in this study can be generally applicable for
      fine-tuning the structure and function of heme proteins. 

PMID- 25969805
TI  - Regioisomer-Free C 4h beta-Tetrakis(tert-butyl)metallo-phthalocyanines:
      Regioselective Synthesis and Spectral Investigations.
AB  - Metal beta-tetrakis(tert-butyl)phthalocyanines are the most commonly used
      phthalocyanines due to their high solubility, stability, and accessibility. They
      are commonly used as a mixture of four regioisomers, which arise due to the tert
      butyl substituent on the beta-position, and to the best of our knowledge, their
      regioselective synthesis has yet to be reported. Herein, the C 4h -selective
      synthesis of beta-tetrakis(tert-butyl)metallophthalocyanines is disclosed. Using
      tetramerization of alpha-trialkylsilyl phthalonitriles with metal salts following
      acid-mediated desilylation, the desired metallophthalocyanines were obtained in
      good yields. Upon investigation of regioisomer-free zinc beta-tetrakis(tert
      butyl)phthalocyanine using spectroscopy, the C 4h single isomer described here
      was found to be distinct in the solid state to zinc beta-tetrakis(tert
      butyl)phthalocyanine obtained by a conventional method. 

PMID- 25969806
TI  - Chemoselective Oxidation of Benzyl, Amino, and Propargyl Alcohols to Aldehydes
      and Ketones under Mild Reaction Conditions.
AB  - Catalytic oxidation reactions often suffer from drawbacks such as low yields and
      poor selectivity. Particularly, selective oxidation of alcohols becomes more
      difficult when a compound contains more than one oxidizable functional group. In
      order to deliver a methodology that addresses these issues, herein we report an
      efficient, aerobic, chemoselective and simplified approach to oxidize a broad
      range of benzyl and propargyl alcohols containing diverse functional groups to
      their corresponding aldehydes and ketones in excellent yields under mild reaction
      conditions. Optimal yields were obtained at room temperature using 1 mmol
      substrate, 10 mol % copper(I) iodide, 10 mol % 4-dimethylaminopyridine (DMAP),
      and 1 mol % 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) in acetonitrile, under
      an oxygen balloon. The catalytic system can be applied even when sensitive and
      oxidizable groups such as alkynes, amines, and phenols are present; starting
      materials and products containing such groups were found to be stable under the
      developed conditions. 

PMID- 25969807
TI  - Efficient Photoelectrochemical Energy Conversion using Spinach Photosystem II
      (PSII) in Lipid Multilayer Films.
AB  - The need for clean, renewable energy has fostered research into photovoltaic
      alternatives to silicon solar cells. Pigment-protein complexes in green plants
      convert light energy into chemical potential using redox processes that produce
      molecular oxygen. Here, we report the first use of spinach protein photosystem II
      (PSII) core complex in lipid films in photoelectrochemical devices. Photocurrents
      were generated from PSII in a ~2 MUm biomimetic dimyristoylphosphatidylcholine
      (DMPC) film on a pyrolytic graphite (PG) anode with PSII embedded in multiple
      lipid bilayers. The photocurrent was ~20 MUA cm(-2) under light intensity 40 mW
      cm(-2). The PSII-DMPC anode was used in a photobiofuel cell with a platinum black
      mesh cathode in perchloric acid solution to give an output voltage of 0.6 V and a
      maximum output power of 14 MUW cm(-2). Part of this large output is related to a
      five-unit anode-cathode pH gradient. With catholytes at higher pH or no
      perchlorate, or using an MnO2 oxygen-reduction cathode, the power output was
      smaller. The results described raise the possibility of using PSII-DMPC films in
      small portable power conversion devices. 

PMID- 25969809
TI  - Sol-gel microspheres doped with glycerol: a structural insight in light of
      forthcoming applications in the polyurethane foam industry.
AB  - Porous silica-based microspheres encapsulating aqueous glycerol can be potential
      curing agents for one-component foams (OCFs). Such agents have the advantage of
      an enhanced sustainability profile on top of being environmentally friendly
      materials. A synthetically convenient and scalable sol-gel process was used to
      make silica and organosilica microspheres doped with aqueous glycerol. These
      methyl-modified silica microspheres, named "GreenCaps", exhibit remarkable
      physical and chemical stability. The microspheres were characterized by scanning
      electron microscopy, transmission electron microscopy at reduced pressure, and
      cryogenic nitrogen adsorption-desorption analysis. The structure of the materials
      was also analyzed at the molecular level by diffuse reflectance infrared Fourier
      transform (DRIFT) spectroscopy. As expected, the degree of methylation affects
      the degree of encapsulation and pore structure. Microspheres similarly
      methylated, however, can differ considerably in surface area and pore size due to
      the templating effect of glycerol on the organosilica structure. The results of
      the structure analysis reveal that glycerol is efficiently encapsulated, acts as
      a template, barely leaches over time, but is released by depressurization. A
      proper application of these microspheres can later on enhance both the
      environmental and health profile, as well as the technical performance (curing
      speed, foam quality, and froth thixotropy) of spray polyurethane foams. 

PMID- 25969808
TI  - Self-assembled functionalized graphene nanoribbons from carbon nanotubes.
AB  - Graphene nanoribbons (GNR) were generated in ethanol solution by unzipping
      pyrrolidine-functionalized carbon nanotubes under mild conditions. Evaporation of
      the solvent resulted in regular few-layer stacks of graphene nanoribbons observed
      by transmission electron microscopy (TEM) and X-ray diffraction. The experimental
      interlayer distance (0.49-0.56 nm) was confirmed by computer modelling (0.51 nm).
      Computer modelling showed that the large interlayer spacing (compared with
      graphite) is due to the presence of the functional groups and depends on their
      concentration. Stacked nanoribbons were observed to redissolve upon solvent
      addition. This preparation method could allow the fine-tuning of the interlayer
      distances by controlling the number and/or the nature of the chemical groups in
      between the graphene layers. 

PMID- 25969810
TI  - A new porphyrin for the preparation of functionalized water-soluble gold
      nanoparticles with low intrinsic toxicity.
AB  - A potential new photosensitizer based on a dissymmetric porphyrin derivative
      bearing a thiol group was synthesized. 5-[4-(11-Mercaptoundecyloxy)-phenyl
      10,15,20-triphenylporphyrin (PR-SH) was used to functionalize gold nanoparticles
      in order to obtain a potential drug delivery system. Water-soluble
      multifunctional gold nanoparticles GNP-PR/PEG were prepared using the Brust
      Schiffrin methodology, by immobilization of both a thiolated polyethylene glycol
      (PEG) and the porphyrin thiol compound (PR-SH). The nanoparticles were fully
      characterized by transmission electron microscopy and (1)H nuclear magnetic
      resonance spectroscopy, UV/Vis absorption spectroscopy, and X-ray photoelectron
      spectroscopy. Furthermore, the ability of GNP-PR/PEGs to induce singlet oxygen
      production was analyzed to demonstrate the activity of the photosensitizer.
      Cytotoxicity experiments showed the nanoparticles are nontoxic. Finally, cellular
      uptake experiments demonstrated that the functionalized gold nanoparticles are
      internalized. Therefore, this colloid can be considered to be a novel nanosystem
      that could potentially be suitable as an intracellular drug delivery system of
      photosensitizers for photodynamic therapy. 

PMID- 25969811
TI  - Synthesis and characterization of layered double hydroxides and their potential
      as nonviral gene delivery vehicles.
AB  - Layered double hydroxides (LDHs) exhibit characteristic anion-exchange chemistry
      making them ideal carriers of negatively charged molecules like deoxyribonucleic
      acid (DNA). In this study, hydrotalcite (Mg-Al) and hydrotalcite-like compounds
      (Mg-Fe, Zn-Al, and Zn-Fe), also known as LDHs, were evaluated for their potential
      application as a carrier of DNA. LDHs were prepared by coprecipitation at low
      supersaturation and characterized by Powder X-ray diffraction (XRD), infrared
      (IR), Raman, and inductively coupled plasma-optical emission spectroscopy,
      scanning electron microscopy (SEM), and transmission electron microscopy (TEM).
      XRD patterns showed strong and sharp diffraction peaks for the (003) and (006)
      planes indicating well-ordered crystalline materials. TEM images yielded
      irregular circular to hexagonal-shaped particles of 50-250 nm in size. Varying
      degrees of DNA binding was observed for all the compounds, and nuclease digestion
      studies revealed that the LDHs afford some degree of protection to the bound DNA.
      Minimal toxicity was observed in human embryonic kidney (HEK293), cervical cancer
      (HeLa) and hepatocellular carcinoma (HepG2) cell lines with most showing a cell
      viability in excess of 80 %. All LDH complexes promoted significant levels of
      luciferase gene expression, with the DNA:Mg-Al LDHs proving to be the most
      efficient in all cell lines. 

PMID- 25969812
TI  - Synthesis and Characterization of CeO2 Nanoparticles via Solution Combustion
      Method for Photocatalytic and Antibacterial Activity Studies.
AB  - CeO2 nanoparticles have been proven to be competent photocatalysts for
      environmental applications because of their strong redox ability, nontoxicity,
      long-term stability, and low cost. We have synthesized CeO2 nanoparticles via
      solution combustion method using ceric ammonium nitrate as an oxidizer and
      ethylenediaminetetraacetic acid (EDTA) as fuel at 450  degrees C. These
      nanoparticles exhibit good photocatalytic degradation and antibacterial activity.
      The obtained product was characterized by various techniques. X-ray diffraction
      data confirms a cerianite structure: a cubic phase CeO2 having crystallite size
      of 35 nm. The infrared spectrum shows a strong band below 700 cm(-1) due to the
      Ce-O-Ce stretching vibrations. The UV/Vis spectrum shows maximum absorption at
      302 nm. The photoluminescence spectrum shows characteristic peaks of CeO2
      nanoparticles. Scanning electron microscopy (SEM) images clearly show the
      presence of a porous network with a lot of voids. From transmission electron
      microscopy (TEM) images, it is clear that the particles are almost spherical, and
      the average size of the nanoparticles is found to be 42 nm. CeO2 nanoparticles
      exhibit photocatalytic activity against trypan blue at pH 10 in UV light, and the
      reaction follows pseudo first-order kinetics. Finally, CeO2 nanoparticles also
      reduce Cr(VI) to Cr(III) and show antibacterial activity against Pseudomonas
      aeruginosa. 

PMID- 25969813
TI  - Computational exploration of the photoprotective potential of gadusol.
AB  - Gadusol shows one of the simplest structures among a series of natural UV
      absorbing compounds that have been related to the photoprotective and antioxidant
      functions in aquatic organisms. CASPT2//CASSCF methodology was used to carry out
      a theoretical study on this basic structure in order to describe the underlying
      features responsible for the photoprotective capacity of the molecule. The
      influence of the enol-enolate equilibrium on the photophysical properties was
      explored. The results confirm that both forms undergo a rapid deactivation, which
      very efficiently dissipates light energy as heat. This work highlights the
      potential of molecular-level studies to provide an understanding of natural
      photoprotective mechanisms and gives support to the future design of structurally
      related new synthetic sunscreens. 

PMID- 25969814
TI  - Halogen and Hydrogen Bonding Benzothiophene Diol Derivatives: A Study Using ab
      initio Calculations and X-Ray Crystal Structure Measurements.
AB  - The aim of this study is to describe and compare the supramolecular interactions,
      in the solid state, of chloro-, bromo-, and iodobenzothiophene diols. The
      compounds were obtained through organo-catalyzed reactions starting from 3
      substituted halobenzothiophene carbaldehydes. Energies of the noncovalent
      interactions were obtained by density functional theory calculations. Bond
      distances and angles were found to be in accordance with those determined by X
      ray structure analysis. anti-Bromobenzothiophene derivatives showed strong
      halogen???pi interactions between bromine and the heterocyclic phenyl ring,
      corresponding to an energy of 7.5 kcal mol(-1). syn-Bromo and syn-iodo
      derivatives appeared to be isostructural, showing X???O (carbonyl) interactions,
      pi stacking, and formation of extended hydrogen bonding networks. In contrast,
      the chloro derivatives displayed no halogen bonding interactions. 

PMID- 25969815
TI  - Assessment of the Full Compatibility of Copper(I)-Catalyzed Alkyne-Azide
      Cycloaddition and Oxime Click Reactions for bis-Labelling of Oligonucleotides.
AB  - The conjugation of oligonucleotides with reporters is of great interest for
      improving their intrinsic properties or endowing new ones. In this context, we
      report herein a new procedure for the bis-labelling of oligonucleotides through
      oxime ligation (Click-O) and copper(I)-catalyzed alkyne-azide cycloaddition
      (Click-H). 5'-Azido and 3'-aldehyde precursors were incorporated into
      oligonucleotides, and subsequent coupling reactions through Click-O and Click-H
      (or vice versa) were successfully achieved. In particular, we exhaustively
      investigated the full compatibility of each required step for both tethering
      strategies. The results demonstrate that click Huisgen and click oxime reactions
      are fully compatible. However, whilst both approaches can deliver the targeted
      doubly conjugated oligonucleotide, the route involving click oxime ligation prior
      to click Huisgen is significantly more successful. Thus the reactions
      investigated here can be considered to be key elements of the chemical toolbox
      for the synthesis of highly sophisticated bioconjugates. 

PMID- 25969816
TI  - Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4
      Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity.
AB  - Affibody molecules are small scaffold-based affinity proteins with promising
      properties as probes for radionuclide-based molecular imaging. However, a high
      reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have
      shown that the use of (125)I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for
      site-specific labeling of cysteine-containing Affibody molecules provides high
      tumor uptake but low radioactivity retention in kidneys. We hypothesized that the
      use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of
      radioactivity because of higher lipophilicity of radiometabolites. An anti-human
      epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was
      labeled using (125)I-IPEM with an overall yield of 45+/-3 %. (125)I-IPEM
      ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells
      (SKOV-3 cell line). In NMRI mice, the renal uptake of (125)I-IPEM-ZHER2:2395
      (24+/-2 and 5.7+/-0.3 % IA g(-1)at 1 and 4 h after injection, respectively) was
      significantly lower than uptake of (125)I-IHPEM-ZHER2:2395 (50+/-8 and 12+/-2 %
      IA g(-1)at 1 and 4 h after injection, respectively). In conclusion, the use of a
      more lipophilic linker for the radioiodination of Affibody molecules reduces
      renal radioactivity. 

PMID- 25969818
TI  - Synthetic studies of alkaloids containing pyrrolidine and piperidine structural
      motifs.

PMID- 25969817
TI  - Gold(III)-pyrrolidinedithiocarbamato Derivatives as Antineoplastic Agents.
AB  - Transition metals offer many possibilities in developing potent chemotherapeutic
      agents. They are endowed with a variety of oxidation states, allowing for the
      selection of their coordination numbers and geometries via the choice of proper
      ligands, leading to the tuning of their final biological properties. We report
      here on the synthesis, physico-chemical characterization, and solution behavior
      of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [Au(III)Br2(PDT)] and
      [Au(III)Cl2(PDT)]. We found that the bromide derivative was more effective than
      the chloride one in inducing cell death for several cancer cell lines.
      [Au(III)Br2(PDT)] elicited oxidative stress with effects on the permeability
      transition pore, a mitochondrial channel whose opening leads to cell death. More
      efficient antineoplastic strategies are required for the widespread burden that
      is cancer. In line with this, our results indicate that [Au(III)Br2(PDT)] is a
      promising antineoplastic agent that targets cellular components with crucial
      functions for the survival of tumor cells. 

PMID- 25969819
TI  - The management of thoracolumbar burst fractures: a prospective study between
      conservative management, traditional open spinal surgery and minimally
      interventional spinal surgery.
AB  - The objective of this study was to assess which patient group had better outcomes
      for management of single level thoracolumbar spinal fractures. We prospectively
      collected data on the outcomes of patients having either conservatively managed,
      traditional open surgery, or minimally interventional surgery (MIS) for treatment
      of a single level thoracolumbar fracture. All patients had previously
      asymptomatic spines prior to their fractures and had a single level thoracolumbar
      burst fracture of more than 20 degrees  kyphosis. Fractures treated operatively,
      either via open surgery or MIS techniques, were corrected to less than 10 degrees
      of residual kyphosis using a monoaxial pedicle screw construct 2 levels above &
      2 levels below the fracture posteriorly only. The metalwork was removed between 6
      months and 1 year post operatively to remobilise the spinal segments. All
      patients were then evaluated at least 6 months after metal work removal and at 18
      months post fracture using radiographs and the Oswestry Disability Index (ODI).
      Those patients treated with MIS techniques demonstrated superior outcomes
      compared to traditional open techniques and conservative methods of treatment,
      with significantly reduced hospital stay, better return to work & leisure, and
      the best chance of restoring their spine to near its pre-injury status. We would
      recommend MIS techniques as the best way of treating single level thoracolumbar
      spinal fractures. There is a significant improvement in ODI when treated by MIS
      over open surgical methods. 

PMID- 25969820
TI  - Association of glutathione S-transferase (GSTM1 and GSTT1) genes with chronic
      myeloid leukemia.
AB  - Chronic myeloid leukemia (CML), as most of cancers results from a complex
      interaction between genetic or non genetic factors. Exposures to xenobiotics
      endogenous or exogenous associated with a reduced individual ability in
      detoxifying activity, constitutes a risk of developing cancer. It is known that
      polymorphism of glutathione S-transferases (GSTs) genes affects the
      detoxification of xenobiotics. Thus, we conducted a case-control study in which
      92 patients (Mean age +/- SD, 40.62 +/- 12.7 years) with CML and 93 healthy
      unrelated controls (Mean age +/- SD, 41.38 +/- 13.4 years) have participated.
      GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction.
      Logistic regression was used to assess the possible link between GSTM1 and GSTT1
      null genotypes and CML as well as between combined genotypes and CML. GSTM1 null
      genotype frequency was slightly higher in patients than control (48.9% vs. 40.9%)
      but, it was not associated with CML (OR 95% CI, 1.4, 0.78-2.48; p = 0.271).
      Moreover, GSTT1 null genotype frequency showed a similar trend between patients
      and control (17.4% vs. 9.7%; OR 95% CI, 1.97, 0.82-4.71; p = 0.13). Surprisingly,
      GSTT1 null genotype was significantly associated with the risk of CML in males
      (OR 95% CI, 5, 1.25-20.1; p = 0.023). The combined GSTM1 present/GSTT1 null
      genotype was found to have a limited effect against the risk of CML (OR 95% CI,
      0.3, 0.08-0.99; p = 0.049). Our findings have shown that GSTT1 null genotype
      might be a risk factor of CML in males. While, GSTT1 present genotype might be
      considered as protective against CML. However, further studies with a large
      sample size are needed to confirm our findings. 

PMID- 25969822
TI  - A case control association study of COMT gene polymorphism (I/D) with type 2
      diabetes and its related factors in Pakistani Punjabi population.
AB  - BACKGROUND: The Catechol-O-Methyl Transferase (COMT) gene polymorphism (I/D of C
      nucleotide at base position 900) has been previously implicated in the
      development of type 2 diabetes (T2D) and kidney disease. So, aim of this study
      was to find association of I/D polymorphism with T2D, and its associated factors
      like family history and nephropathy (End Stage Renal Disease, ESRD) patients in a
      cohort of Pakistani Punjabis. METHODS: Genomic DNA was extracted from human
      subjects divided as four study groups: controls (n = 46), diabetics (n = 46),
      diabetics with nephropathy/ESRD (n = 53), and non-diabetics without
      nephropathy/ESRD (n = 43). The 900 I/D C polymorphism in the COMT gene was tested
      by PCR-RFLP method. Genotype and allele frequencies as well as Odds Ratios were
      calculated for these groups. Groups were compared statistically for the analysis
      of genotypes, alleles, biochemical parameters as well as disease status. RESULTS:
      In comparison with control group (non-diabetic, non-nephropathy), there was no
      significant difference in rest of the three groups for allele or genotype
      frequencies of COMT gene. However, Chi square (chi(2)) analysis identified a
      significant (p = 0.02) correlation of the 900 I/D C polymorphism with family
      history of diabetes, as it was found that greater number (74%) of patients having
      I allele had a positive family history of T2D. CONCLUSIONS: A significant
      correlation of the COMT polymorphism (900 I/D C) with the family history of T2D
      has been observed, which has not been previously reported in Pakistani Punjabi
      population, however, this preliminary finding requires further validation
      studies.

PMID- 25969821
TI  - The effect of topical olive oil on the healing of foot ulcer in patients with
      type 2 diabetes: a double-blind randomized clinical trial study in Iran.
AB  - BACKGROUND: Diabetic Foot Ulcer (DFU) is the most costly and devastating
      complication of diabetes mellitus which can lead to infection, gangrene,
      amputation, and even death if the necessary care is not provided. Nowadays, some
      herbal products have shown therapeutic effects on healing of DFU. So, this study
      aimed to assess the effects of topical olive oil on the healing of DFU. METHODS:
      This double-blind randomized clinical trial study was conducted in Diabetes
      Clinic of Ahvaz Golestan hospital, Iran, in 2014. Thirty-four patients with DFU
      of Wagner's ulcer grade 1 or 2 were enrolled in this study. Patients who were
      randomly assigned to intervention group (n = 17) received topical olive oil in
      addition to routine cares, whereas patients in control group (n = 17) just
      received routine cares. Intervention was done once a day for 4 weeks in both
      groups, and in the end of each week; the ulcers were assessed and scored. Data
      was collected by demographic and clinical characteristics checklists as well as
      diabetic foot ulcer healing checklist, and was analyzed by SPSS version 19
      software using descriptive (mean and standard deviation) and analytic (student's
      sample t-test, chi-square and repeated-measures analysis of variance) statistics.
      RESULTS: At the end of 4(th) week, there was a significant differences between
      two groups regarding to 3 parameters of ulcer including degree (P = 0.03), color
      (P = 0.04) and surrounding tissues (P < 0.001) as well as total status of ulcer
      (P = 0.001), while related to ulcer drainages no significant difference was seen
      between the two groups (P = 0.072). At the end of the follow up, olive oil
      significantly decreased ulcer area (P = 0.01) and depth (P = 0.02) compared with
      control group. Complete ulcer healing in the intervention group was significantly
      greater than control group (73.3% vs. 13.3%, P = 0.003) at the end of follow up.
      Also, there were no adverse effects to report during the study in intervention
      group. CONCLUSIONS: Our results indicated that olive oil in combination with
      routine cares is more effective than routine cares alone, and is without any side
      effect. However, further studies are required in the future to confirm these
      results. TRIAL REGISTRATION: IRCT2014083014251N2.

PMID- 25969823
TI  - Effects of Photoperiod on Epididymal and Sperm Morphology in a Wild Rodent, the
      Viscacha (Lagostomus maximus maximus).
AB  - The viscacha (Lagostomus maximus maximus) is a seasonal South American wild
      rodent. The adult males exhibit an annual reproductive cycle with periods of
      maximum and minimum gonadal activity. Four segments have been identified in the
      epididymis of this species: initial, caput, corpus, and cauda. The main objective
      of this work was to relate the seasonal morphological changes observed in the
      epididymal duct with the data from epididymal sperm during periods of activity
      and gonadal regression using light and scanning electron microscopy (SEM). Under
      light and electron microscopy, epididymal corpus and cauda showed marked seasonal
      variations in structural parameters and in the distribution of different cellular
      populations of epithelium. Initial and caput segments showed mild morphological
      variations between the two periods. Changes in epididymal sperm morphology were
      observed in the periods analyzed and an increased number of abnormal gametes were
      found during the regression period. During this period, anomalies were found
      mainly in the head, midpiece, and neck, while in the activity period, defects
      were found only in the head. Our results confirm that the morphological
      characteristics of the epididymal segments, as well as sperm morphology, undergo
      significant changes during the reproductive cycle of Lagostomus. 

PMID- 25969824
TI  - Study of position, shape, and size of mental foramen utilizing various parameters
      in dry adult human mandibles from north India.
AB  - Background. As the mental foramen (MF) is an important landmark to facilitate
      surgical, local anesthetic, and other invasive procedures, the present study was
      aimed to elucidate its morphological features and morphometric parameters with
      reference to surrounding landmarks. Material and Method. 105 dry adult human
      mandibles of unknown sex were observed for position, shape, and number of mental
      foramina. Their size was measured using a digital vernier caliper and
      statistically analyzed by mean and standard deviations (SD). Results. In most
      cases (74.3%), the MF was oval in shape and situated on the longitudinal axis of
      the 2nd premolar tooth (61% on right side and 59.1% on left side). The mean
      distance for the right and left sides was measured from various landmarks.
      Conclusion. Prior knowledge of mental foramen variations helps surgeons in
      planning surgery in that region to avoid nerve damage and also enable effective
      mental nerve block anesthesia. 

PMID- 25969825
TI  - Branching pattern of inferior mesenteric artery in a black african population: a
      dissection study.
AB  - Background. Branching pattern of inferior mesenteric artery (IMA) and pattern of
      vascular supply to the left colon and rectosigmoid areas, though important during
      colorectal surgery, display interethnic variations. Further, these regions have
      notable vascular "weak points" reported to be highly susceptible to ischemic
      colitis. This study aimed at evaluating the branching pattern of IMA in a black
      African population. Materials and Methods. Fifty-seven formalin-embalmed cadavers
      (28 Male, 27 Female) were studied. The length, branching pattern, and diameter of
      IMA at its origin were recorded. Results. IMA mean length and diameter at origin
      were 30.57 +/- 10.0 mm and 4.10 +/- 0.9 mm, respectively. IMA most frequently
      branched into left colic artery and a common sigmoid trunk in 23 cases while the
      classical branching pattern was observed in only 7 cases. Colic marginal artery
      was absent at the splenic flexure and sigmoid colon in 7 and 5 cases,
      respectively. Arc of Riolan was observed in 9 cases. Conclusion. Branching
      pattern of IMA shows variations from the previously reported cases which might
      help account for some of the untoward outcomes observed following colon surgery.
      An angiographic study to further delineate functionality of the arterial
      anastomoses in this region is recommended. 

PMID- 25969826
TI  - Posterior cord of brachial plexus and its branches: anatomical variations and
      clinical implication.
AB  - Background. Knowledge of anatomical variations of posterior cord and its branches
      is important not only for the administration of anaesthetic blocks but also for
      surgical approaches to the neck, axilla, and upper arm. The present study aimed
      to record the prevalence of such variations with embryological explanation and
      clinical implication. Material and Method. 37 formalin-preserved cadavers, that
      is, 74 upper extremities from the Indian population, constituted the material for
      the study. Cadavers were dissected during routine anatomy classes for medical
      undergraduate. Dissection includes surgical incision in the axilla, followed by
      retraction of various muscles, to observe and record the formation and branching
      pattern of posterior cord of brachial plexus. Results. Posterior cord was formed
      by union of posterior division of C5 and C6 roots with posterior division of
      middle and lower trunk (there was no upper trunk) in 16.2% of upper extremities.
      Posterior cord of brachial plexus was present lateral to the second part of
      axillary artery in 18.9% of upper extremities. Axillary nerve was taking origin
      from posterior division of upper trunk in 10.8% upper extremities and
      thoracodorsal nerve arising from axillary nerve in 22.9% upper extremities.
      Conclusion. It is important to be aware of such variations while planning a
      surgery in the region of axilla as these nerves are more liable to be injured
      during surgical procedures. 

PMID- 25969827
TI  - The dysregulation profile predicts cannabis use in the offspring of teenage
      mothers.
AB  - Background. Offspring of teenage mothers are at greater risk of early drug use.
      Research has identified a child behavior checklist (CBCL) profile for children
      with high levels of comorbid behavior problems, the dysregulation profile (DP),
      as another risk factor for drug use. Method. Teenage girls (12-18 years old; 71%
      African-American, 29% White) were recruited during pregnancy. Data were collected
      during pregnancy and when offspring were 6, 10, and 14 years old (n = 318).
      Mothers completed the CBCL when children were at ages 6 and 10, and children who
      scored 60 or higher on all 3 DP subscales (aggression, anxiety/depression, and
      attention problems) were categorized as dysregulated. At ages 10 and 14, the
      offspring (50% male, 50% female) reported on their cannabis use and completed the
      childhood depression inventory (CDI). Results. DP at age 6 and depressive
      symptoms at age 14 predicted recent cannabis use in the offspring. There was a
      significant interaction between race and pubertal timing such that White
      offspring who matured earlier were at greater risk of recent cannabis use.
      Conclusions. The results of this study suggest that it may be possible to
      identify a subset of children at risk of dual diagnosis as early as age 6. 

PMID- 25969828
TI  - Male adolescent substance use disorder and attention-deficit hyperactivity
      disorder: a review of the literature.
AB  - Approximately, one-third of male adolescents in treatment for a substance use
      disorder (SUD) also have an Attention-Deficit Hyperactivity Disorder (ADHD). This
      strongly suggests that ADHD is a major risk factor for the development of SUD
      which practitioners must address if they are to provide adequate treatment for
      adolescents with SUD/ADHD. This paper supports a causal role for ADHD in the
      development of SUD and examines the developmental mechanisms whereby ADHD
      increases risk for SUD. These mechanisms include increased risk for conduct
      disorder, academic failure, deviant peer affiliation, engaging in risk behaviors,
      and self-medication. Assessment and treatment recommendations for those comorbid
      for SUD/ADHD are provided. 

PMID- 25969829
TI  - What aspect of dependence does the fagerstrom test for nicotine dependence
      measure?
AB  - Although the Fagerstrom Test for Nicotine Dependence (FTND) and the Heaviness of
      Smoking Index (HSI) are widely used, there is a uncertainty regarding what is
      measured by these scales. We examined associations between these instruments and
      items assessing different aspects of dependence. Adult current smokers (n = 422,
      mean age 33.3 years, 61.9% female) completed a web-based survey comprised of
      items related to demographics and smoking behavior plus (1) the FTND and HSI; (2)
      the Autonomy over Tobacco Scale (AUTOS) with subscales measuring Withdrawal,
      Psychological Dependence, and Cue-Induced Cravings; (3) 6 questions tapping
      smokers' wanting, craving, or needing experiences in response to withdrawal and
      the latency to each experience during abstinence; (4) 3 items concerning how
      smokers prepare to cope with periods of abstinence. In regression analyses the
      Withdrawal subscale of the AUTOS was the strongest predictor of FTND and HSI
      scores, followed by taking precautions not to run out of cigarettes or smoking
      extra to prepare for abstinence. The FTND and its six items, including the HSI,
      consistently showed the strongest correlations with withdrawal, suggesting that
      the behaviors described by the items of the FTND are primarily indicative of a
      difficulty maintaining abstinence because of withdrawal symptoms. 

PMID- 25969830
TI  - Significant others, knowledge, and belief on smoking as factors associated with
      tobacco use in italian adolescents.
AB  - Tobacco use is dramatically increasing among youth. Growing attention has been
      addressed towards possible predictors of smoking in such a population. We
      evaluated a sample of Italian adolescents to verify whether adults and peers
      might influence their smoking status. Cross-sectional study was conducted in 16
      schools of North Italy. Data were collected from 2001 to 2010 by means of a self
      administered questionnaire on sociodemographic data and individual/social
      possible predictors of smoking. 2,444 students (56.7% boys; 43.3% girls; mean =
      14.32 +/- 1.384 years) were analysed. 607 (24.8%) were current smokers; 1,837
      (75.2%) were nonsmokers. The presence of smokers in the family, seeing teachers
      who smoke, the influence of friends, and the feeling of inferiority were
      predictors of youth smoking as well as unawareness of nicotine dangerous action
      to health. Running the logistic multivariate analysis with all the variables
      listed above in the same model, the strongest predictors of smoking were as
      follows: being unaware that pipe/cigar is harmful to health as cigarettes; not
      knowing that passive smoking is harmful to the growth of children; having seen
      teachers smoking. The present findings help to identify the variables that might
      favour smoking in youth. Such variables should become the target of prevention
      programs. 

PMID- 25969831
TI  - Deficits of affect mentalization in patients with drug addiction: theoretical and
      clinical aspects.
AB  - Traditionally treated with wariness, drug addictions have provoked a serious
      interest in psychodynamically oriented clinicians in recent decades. This paper
      discusses the development of contemporary psychodynamic conceptualizations of
      addictions, focusing specifically on mentalization-based theories. The concept of
      mentalization refers to a complex form of self-regulation which includes
      attribution of psychological meaning to one's own behavior and affective states,
      as well as those of the others. We hypothesize that drug-addicted patients have
      severe impairments in mentalizing, associated with developmental deficits,
      characteristic for the borderline personality disorder and psychosomatic
      conditions. Psychodynamic models of mentalization and their corresponding
      research operationalizations are reviewed, and implications for a contemporary
      understanding of drug addictions and psychotherapy are drawn. The authors propose
      that mentalization-oriented theories provide an adequate conceptualization, which
      is open to empirical testing and has clear and pragmatic guidelines for
      treatment. 

PMID- 25969833
TI  - Pharmacodynamics must inform statistics: an example from a cocaine dependence
      pharmacotherapy trial.
AB  - Background. There is no FDA-approved medication for cocaine dependence or
      consensus on the statistical approach for analyzing data from cocaine dependence
      pharmacotherapy trials. The goal of this paper is to illustrate the importance of
      understanding medication's pharmacodynamics when specifying the statistical model
      to test its efficacy. Method. Data from a double-blind placebo controlled trial
      of reserpine for cocaine dependence are analyzed. Since the antihypertensive
      properties of reserpine are well established, blood pressure data are utilized to
      evaluate the ability of two statistical models, one that does not take the
      pharmacodynamics of reserpine into account and one that does, to detect
      reserpine's antihypertensive effect. Results. The statistical model specified
      without regard to reserpine's pharmacodynamics failed to find a significant
      medication effect for either systolic (P = 0.49) or diastolic (P = 0.59) blood
      pressure. Contrariwise, the model based on the pharmacodynamics of reserpine
      found a significant effect for both systolic (P = 0.002) and diastolic (P =
      0.004) blood pressure. Conclusions. If the pharmacodynamics of a study medication
      are not considered when specifying statistical models, then erroneous conclusions
      may be reached. This trial is registered with NCT00033033. 

PMID- 25969832
TI  - The choice of screening instrument matters: the case of problematic cannabis use
      screening in spanish population of adolescents.
AB  - The aim of this study was to examine the feasibility of problem cannabis use
      screening instruments administration within wide school surveys, their
      psychometric properties, overlaps, and relationships with other variables.
      Students from 7 Spanish regions, aged 14-18, who attended secondary schools were
      sampled by two-stage cluster sampling (net sample 14,589). Standardized,
      anonymous questionnaire including DSM-IV cannabis abuse criteria, Cannabis Abuse
      Screening Test (CAST), and Severity of Dependence Scale (SDS) was self-completed
      with paper and pencil in the selected classrooms. Data was analysed using
      classical psychometric theory, bivariate tests, and multinomial logistic
      regression analysis. Not responding to instruments' items (10.5-12.3%) was
      associated with reporting less frequent cannabis use. The instruments overlapped
      partially, with 16.1% of positives being positive on all three. SDS was more
      likely to identify younger users with lower frequency of use who thought habitual
      cannabis use posed a considerable problem. CAST positivity was associated with
      frequent cannabis use and related problems. It is feasible to use short
      psychometric scales in wide school surveys, but one must carefully choose the
      screening instrument, as different instruments identify different groups of
      users. These may correspond to different types of problematic cannabis use;
      however, measurement bias seems to play a role too. 

PMID- 25969834
TI  - The Association between Serum LDL Cholesterol and Genetic Variation in
      Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients.
AB  - BACKGROUND: Several polymorphisms of a locus on chromosome 1p13.3 have a
      significant effect on low-density lipoprotein cholesterol (LDL-C),
      atherosclerosis, and acute coronary syndrome (ACS). METHODS: We aimed to
      investigate the association between rs599839, rs646776, and rs4970834 of locus
      1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients.
      Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed
      on Arab patients undergoing coronary angiography for ACS. Patients were divided
      into group A (ACS with insignificant stenosis (<50%)) and group B (with
      significant stenosis (>= 50%)). RESULTS: Patients carrying the minor G allele in
      rs599839 had significantly lower mean of LDL-C (2.58 versus 3.44 mM, P = 0.026)
      than homozygous A allele carriers (GG versus AA). Carriers of minor C allele in
      rs64776 had significantly higher mean of HDL-C (2.16 versus 1.36 mM, P = 0.004)
      than carriers of the T alleles (AA versus GG). The odd ratio and 95% confidence
      interval for dominant model for G allele carriers of rs599839 were 0.51 (0.30
      0.92), P = 0.038, among patients with significant stenosis. CONCLUSIONS:
      Polymorphisms rs646776 and rs599839 of locus 1p13.3 were significantly associated
      with LDL-C and other lipid parameters. In addition, the G-allele carriers of
      variant rs599839 had a significant protective effect against the atherosclerosis.

PMID- 25969835
TI  - Peripheral blood mononuclear cell proteome changes in patients with
      myelodysplastic syndrome.
AB  - Our aim was to search for proteome changes in peripheral blood mononuclear cells
      (PBMCs) of MDS patients with refractory cytopenia with multilineage dysplasia.
      PBMCs were isolated from a total of 12 blood samples using a Histopaque-1077
      solution. The proteins were fractioned, separated by 2D SDS-PAGE (pI 4-7), and
      double-stained. The proteomes were compared and statistically processed with
      Progenesis SameSpots; then proteins were identified by nano-LC-MS/MS. Protein
      functional association and expression profiles were analyzed using the EnrichNet
      application and Progenesis SameSpots hierarchical clustering software,
      respectively. By comparing the cytosolic, membrane, and nuclear fractions of the
      two groups, 178 significantly (P < 0.05, ANOVA) differing spots were found,
      corresponding to 139 unique proteins. Data mining of the Reactome and KEGG
      databases using EnrichNet highlighted the possible involvement of the identified
      protein alterations in apoptosis, proteasome protein degradation, heat shock
      protein action, and signal transduction. Western blot analysis revealed
      underexpression of vinculin and advanced fragmentation of fermitin-3 in MDS
      patients. To the best of our knowledge, this is the first time that proteome
      changes have been identified in the mononuclear cells of MDS patients. Vinculin
      and fermitin-3, the proteins involved in cell adhesion and integrin signaling,
      have been shown to be dysregulated in MDS. 

PMID- 25969838
TI  - Novel computational tools in biosignal processing.

PMID- 25969837
TI  - Increased frequency of CD4+ CD25+ FoxP3+ T regulatory cells in pulmonary
      tuberculosis patients undergoing specific treatment and its relationship with
      their immune-endocrine profile.
AB  - Tuberculosis (TB) is a major health problem requiring an appropriate cell immune
      response (IR) to be controlled. Since regulatory T cells (Tregs) are relevant in
      IR regulation, we analyzed Tregs variations throughout the course of TB treatment
      and its relationship with changes in immune-endocrine mediators dealing with
      disease immunopathology. The cohort was composed of 41 adult patients, 20 of them
      completing treatment and follow-up. Patients were bled at diagnosis (T0) and at 2
      (T2), 4 (T4), 6 (T6), and 9 months following treatment initiation. Twenty-four
      age- and sex-matched healthy controls (HCo) were also included. Tregs (flow
      cytometry) from TB patients were increased at T0 (versus HCo P < 0.05), showing
      even higher values at T2 (versus T0 P < 0.01) and T4 (versus T0 P < 0.001). While
      IL-6, IFN-gamma, TGF-beta (ELISA), and Cortisol (electrochemiluminescence, EQ)
      were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo,
      with cytokines and Cortisol returning to normal values at T9. Tregs correlated
      positively with IFN-gamma (R = 0.868, P < 0.05) at T2 and negatively at T4 (R = 
      0.795, P < 0.05). Lowered levels of proinflammatory cytokines together with an
      increased frequency of Tregs of patients undergoing specific treatment might
      reflect a downmodulatory effect of these cells on the accompanying inflammation. 

PMID- 25969836
TI  - Experimental autoimmune encephalomyelitis development is aggravated by Candida
      albicans infection.
AB  - Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central
      nervous system (CNS) mainly mediated by myelin specific T cells. It is widely
      believed that environmental factors, including fungal infections, contribute to
      disease induction or evolution. Even though Candida infection among MS patients
      has been described, the participation of this fungus in this pathology is not
      clear. The purpose of this work was to evaluate the effect of a Candida albicans
      infection on experimental autoimmune encephalomyelitis (EAE) that is a widely
      accepted model to study MS. Female C57BL/6 mice were infected with C. albicans
      and 3 days later, animals were submitted to EAE induction by immunization with
      myelin oligodendrocyte glycoprotein. Previous infection increased the clinical
      score and also the body weight loss. EAE aggravation was associated with
      expansion of peripheral CD4(+) T cells and production of high levels of TNF
      alpha, IFN-gamma IL-6, and IL-17 by spleen and CNS cells. In addition to yeast
      and hyphae, fungus specific T cells were found in the CNS. These findings suggest
      that C. albicans infection before EAE induction aggravates EAE, and possibly MS,
      mainly by CNS dissemination and local induction of encephalitogenic cytokines.
      Peripheral production of encephalitogenic cytokines could also contribute to
      disease aggravation. 

PMID- 25969839
TI  - Goodbye and thank you.

PMID- 25969840
TI  - Can application of universal primers alone be a substitute for airborne-particle
      abrasion to improve adhesion of resin cement to zirconia?
AB  - PURPOSE: To determine whether universal primers alone can deliver similar levels
      of adhesion of resin cement to zirconia ceramic when compared to their
      application in conjunction with airborne-particle abrasion. MATERIALS AND
      METHODS: Sintered zirconia blocks (N = 160) (Lava, 3M ESPE), (5.25 * 5.25 * 3
      mm3) were embedded in acrylic resin, polished, and randomly distributed into 16
      groups (n = 10 per group), according to the factors "universal primer" (8 levels)
      and "air-particle abrasion" (2 levels): 1. ctr: control, without application of a
      universal primer; 2. AP: Alloy Primer; 3. MP: Monobond Plus; 4. MZP: Metal
      Zirconia Primer; 5. MZ: MZ Primer; 6. Sg: Signum Zirconia Bond; 7. SbU:
      Singlebond Universal; 8. ZP: Z Prime Plus. The universal primers were also used
      after air abrasion (A) of zirconia to form the following 8 groups: Ctr-A, AP-A,
      MP-A, MZP-A, MZ-A, Sg-A, SbU-A, and ZP-A. After ultrasonic cleaning, air abrasion
      was performed using Al2O3 particles (110 MUm, 2.5 bar, 20 s at 10 mm) in a
      chairside air-abrasion device. After ultrasonic cleaning again, universal primers
      were applied according to each manufacturer's recommendation. The resin cement
      (RelyX ARC, 3M ESPE) was built up incrementally and photopolymerized on the
      zirconia surface using a silicone mold (O = 3.5, height = 3 mm). All specimens
      were stored in distilled water (60 days at 37 degrees C) and then subjected to
      shear bond strength testing (SBS) in a universal testing machine (1 mm/min). On a
      separate set of zirconia specimens, contact angle measurements were made using
      the sessile drop technique with a goniometer after the application of universal
      primers on control and air-abraded zirconia surfaces. Data (MPa) were analyzed
      using one-way ANOVA, Tukey's test, and Student's t-test (alpha = 0.05). RESULTS:
      When universal primers were used alone, SbU presented significantly higher mean
      SBS (19.5 +/- 5.8) that did the other primers (0 to 9.9 +/- 6.6) (p = 0.001).
      When air abraded, the groups AP-A (14.1 +/- 6.1), MP-A (15.9 +/- 5.4), ZP-A (16.9
      +/- 7.3), SG-A (19.1 +/- 2.1), SbU-A (12 +/- 1.5) showed significant differences
      (p = 0.03). Adhesive performance of all universal primers was enhanced after air
      abrasion, with the exception of the SbU and MZ primers. After air abrasion,
      contact angle measurements were lower for the each primer (without air abrasion:
      28.9 to 83.9; with air abrasion: 27.1 to 63.0), except for MZP. CONCLUSION: Air
      abrasion with 110 MUm Al2O3 followed by universal primer application increased
      the bond strength of tested resin cement to zirconia, with the exception of SbU
      and MZ.

PMID- 25969842
TI  - Intraoral repair protocol for chipping or fracture of veneering ceramic in
      zirconia fixed dental prostheses.

PMID- 25969843
TI  - A new route towards colloidal molecules with externally tunable interaction
      sites.
AB  - We describe a route towards self-assembled colloidal molecules, where
      thermoresponsive microgels serve as discrete, externally tunable interaction
      sites. The ability of poly(N-isopropylacrylamide) (PNIPAM) and poly(N
      isopropylmethacrylamide) (PNIPMAM) microgels to adsorb to the oil/water (O/W)
      interface and create Pickering-stabilized mini-emulsions was first tested using
      the controlled addition of sub-micron-sized polydimethylsiloxane (PDMS) oil
      droplets to a microgel suspension. The use of a mixture of PNIPAM and PNIPMAM
      microgels differing in size and fluorescent labeling then resulted in the
      formation of thermosensitive patchy particles, where the patches can be
      visualised using fluorescence confocal laser scanning microscopy. The size of the
      assembled decorated droplets and the number of adsorbed microgels was further
      reduced using an in situ synthesis approach, where the oil droplets are directly
      synthesised in the presence of microgels. This results in the formation of highly
      monodisperse microgel-decorated PDMS oil droplets with a small number of
      microgels adsorbed to the droplet interface. We demonstrate that we can use
      temperature to change the interaction potential between these interaction sites
      and thus trigger a reversible association of the individual decorated droplets at
      temperatures above the volume phase transition temperature TVPT of the microgels.
      Finally, we investigated the temporal evolution of the decorated droplets and
      found that small and well-defined clusters of microgels form in the early stages
      of the process primarily through the action of capillary forces. These clusters
      mimic colloidal molecules with a small number of discrete and thermosensitive
      binding sites. 

PMID- 25969844
TI  - Motility induced changes in viscosity of suspensions of swimming microbes in
      extensional flows.
AB  - Suspensions of motile cells are model systems for understanding the unique
      mechanical properties of living materials which often consist of ensembles of
      self-propelled particles. We present here a quantitative comparison of theory
      against experiment for the rheology of such suspensions in extensional flows. The
      influence of motility on viscosities of cell suspensions is studied using a novel
      acoustically-driven microfluidic capillary-breakup extensional rheometer.
      Motility increases the extensional viscosity of suspensions of algal pullers, but
      decreases it in the case of bacterial or sperm pushers. A recent model
      [Saintillan, Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2010, 81, 56307]
      for dilute active suspensions is extended to obtain predictions for higher
      concentrations, after independently obtaining parameters such as swimming speeds
      and diffusivities. We show that details of body and flagellar shape can
      significantly determine macroscale rheological behaviour. 

PMID- 25969845
TI  - Mesoscale modelling of environmentally responsive hydrogels: emerging
      applications.
AB  - Stimuli-sensitive hydrogels are an exciting class of materials with widespread
      potential for use in engineering and biomedical applications. The design of
      advanced functional devices using hydrogels requires an in-depth understanding of
      the physics and behaviour of such materials. While theoretical tools exist, they
      are often limited to simple cases. Thus, computational methods are necessary to
      model the complex unsteady physics of hydrogels with high fidelity. Mesoscale
      modelling is an emerging approach that enables simulations of polymeric
      structures at length and time scales in between those of molecular dynamics and
      continuum methods. In this feature article, we review various computational
      approaches to model responsive hydrogels and specifically focus on dissipative
      particle dynamics (DPD), a particle-based mesoscale method. We discuss several
      approaches for modelling cross-linked polymer networks in DPD, and describe
      recent applications of DPD to modelling hydrogel systems. 

PMID- 25969846
TI  - A dual functional analytical device for self-powered point of care testing and
      electric energy storage.
AB  - A dual functional analytical device performing both energy conversion and
      electric energy storage based on biofuel cells to implement self-powered point-of
      care testing was developed based on a piece of Ti foil. 

PMID- 25969847
TI  - Structure transition of Au18 from pyramidal to a hollow-cage during soft-landing
      onto a TiO2(110) surface.
AB  - Au18 is a unique gold cluster in that, in the gas phase, two distinct isomers,
      namely, golden hollow-cage and golden pyramid, can coexist (ACS Nano, 2009, 3,
      1225). We perform a Born-Oppenheimer molecular dynamics (BOMD) simulation to
      confirm the structural stability of the two isomers at ambient temperature. Most
      importantly, we study the possible structure conversion between the two isomers
      when they are soft-landed onto a rutile TiO2(110) surface. Our BOMD simulation
      indicates that the Au18 cluster can undergo a transition from pyramidal to a
      hollow-cage structure during soft landing onto the rutile TiO2(110) surface at
      ambient temperature, suggesting the high selectivity of the hollow-cage structure
      over the pyramidal structure in realistic soft-landing experiments. 

PMID- 25969849
TI  - Author response.

PMID- 25969848
TI  - Cardiovascular imaging 2014 in the International Journal of Cardiovascular
      Imaging.

PMID- 25969850
TI  - Author response.

PMID- 25969851
TI  - Reflections: neurology and the humanities. A concussion and a photo dilemma.

PMID- 25969852
TI  - Boceprevir: serious haematological disorders.

PMID- 25969853
TI  - Colchicine: more deaths.

PMID- 25969854
TI  - Fluorouracil: dosing errors with infusion pumps.

PMID- 25969855
TI  - Brian Solomon.

PMID- 25969856
TI  - Quantification of NSW Ambulance Record Linkages with Multiple External Datasets.
AB  - This study has two aims: 1) to describe linkage rates between ambulance data and
      external datasets for "episodes of care" and "patient only" linkages in New South
      Wales (NSW), Australia; and 2) to detect and report any systematic issues with
      linkage that relate to patients, and operational or clinical variables that may
      introduce bias in subsequent studies if not adequately addressed. During 2010-11,
      the Centre for Health Record Linkage (CHeReL) in NSW, linked the records for
      patients attended by NSW Ambulance paramedics for the period July 2006 to June
      2009, with four external datasets: Emergency Department Data Collection; Admitted
      Patient Data Collection; NSW Registry of Births, Deaths and Marriages death
      registration data; and the Australian Bureau of Statistics mortality data. This
      study reports linkage rates in terms of those "expected" to link and those who
      were "not expected" to link with external databases within 24 hours of paramedic
      attendance. Following thorough data preparation processes, 2,041,728 NSW
      Ambulance care episodes for 1,116,509 patients fulfilled the inclusion criteria.
      The overall episode-specific hospital linkage rate was 97.2%. Where a patient was
      not transported to hospital following paramedic care, 8.6% of these episodes
      resulted in an emergency department attendance within 24 hours. For all care
      episodes, 5.2% linked to a death record at some time within the 3-year period,
      with 2.4% of all death episodes occurring within 7 days of a paramedic encounter.
      For NSW Ambulance episodes of care that were expected to link to an external
      dataset but did not, nonlinkage to hospital admission records tended to decrease
      with age. For all other variables, issues relating to rates of linkage and
      nonlinkage were more indiscriminate. This quantification of the limitations of
      this large linked dataset will underpin the interpretation and results of ensuing
      studies that will inform future clinical and operational policies and practices
      at NSW Ambulance.

PMID- 25969857
TI  - Alcohol Dehydrogenase-Catalyzed Gold Nanoparticle Seed-Mediated Growth Allows
      Reliable Detection of Disease Biomarkers with the Naked Eye.
AB  - Here, we reported a strategy-based plasmonic enzyme-linked immunosorbent assay
      (ELISA) using alcohol dehydrogenase-catalyzed gold nanoparticle seed-mediated
      growth to serve as a colorimetric signal generation method for detecting disease
      biomarkers with the naked eye. This system possesses the advantages of
      outstanding robustness, sensitivity, and universality. By using this strategy, we
      investigated the hepatitis B surface antigen (HBsAg) and alpha-fetoprotein (AFP)
      with the lowest concentration of naked-eye detection down to 1.0 * 10(-12) g mL(
      1). Experiments with real serum samples from HBsAg-infected patients are
      presented, demonstrating the potential for clinical analysis. Our method
      eliminates the need for sophisticated instruments and high detection expenses,
      making it possible to be a reliable alternative in resource-constrained regions. 

PMID- 25969858
TI  - Biological responses in rats exposed to mainstream smoke from a heated cigarette
      compared to a conventional reference cigarette.
AB  - The heated cigarette (HC) generates mainstream smoke by vaporizing the components
      of the tobacco rod using a carbon heat source at the cigarette tip. Mainstream
      smoke of HC contains markedly less chemical constituents compared to combusted
      cigarettes. Mainstream smoke from HC was generated under Health Canada Intense
      regimen and its biological effects were compared to those of Reference (3R4F)
      cigarettes, using nose-only 5-week and 13-week inhalation studies. In the 13-week
      study, SD rats were necropsied following exposure to mainstream smoke from each
      cigarette at 200, 600 or 1000 ug wet total particulate matter/L for 1 h/day, 7
      days/week or following a 13-week recovery period. Histopathological changes in
      the respiratory tract were significantly lesser in HC groups; e.g. respiratory
      epithelial hyperplasia in the nasal cavity and accumulation of pigmented
      macrophages in alveoli. After a 13-week recovery, the lesions were completely or
      partially regressed, except for accumulation of pigmented macrophages in alveoli,
      in both HC and 3R4F groups. In the 5-week study, SD rats were necropsied
      following exposure to mainstream smoke of either cigarette at 600 or 1000 ug/L
      for 1 h, two times/day (with 30 min interval), 7 days/week or following a 4-week
      recovery period. Bronchoalveolar lavage fluid (BALF) analysis of neutrophil
      percentages and enzyme levels like gamma-GT, ALP and LDH indicated that pulmonary
      inflammation was significantly less in HC groups compared to 3R4F groups. In
      conclusion, HC demonstrated significantly lower biological effects compared to
      3R4F, based on the BALF parameters and histopathology. 

PMID- 25969859
TI  - 2-Chloroacetamidine, a novel immunomodulator, suppresses antigen-induced mouse
      airway inflammation.
AB  - BACKGROUND: Citrullination is a presently under-recognized posttranslational
      protein modification catalyzed by PAD enzymes. Immune responses to citrullinated
      neo-epitopes are identified in a growing number of inflammatory and autoimmune
      diseases. However, the involvement of hypercitrullination in the pathogenesis of
      bronchial asthma is still unknown. METHODS: As main experimental tool, we
      examined the effect of 2-chloroacetamidine (2CA), a PAD enzyme inhibitor, on OVA
      immunized and airway-challenged BALB/c mice; a commonly used model of allergic
      airway inflammation. We also measured the effect of 2CA on ex vivo lymphocytes
      and cell lines. RESULTS: In vivo, 2CA dramatically suppressed lung tissue
      hypercitrullination, inflammatory cell recruitment, and airway-Th2 cytokine
      secretion. 2CA also suppressed systemic OVA-specific and total IgE production
      dramatically, effectively preventing de novo and diminishing established disease
      without measurably impacting general immunocompetence. In vitro, 2CA markedly
      inhibited the proliferation of mouse and human T cells with cell cycle block and
      apoptosis during a limited, postactivation phase. CONCLUSIONS: 2CA acts as narrow
      spectrum immunosuppressant that selectively targets lymphocyte populations
      involved in active inflammatory tissue lesions. If hypercitrullination is
      generated in patients with asthma, 2CA may represent a novel disease modulator
      for human asthmatics/allergic diseases.

PMID- 25969860
TI  - Polydopamine-Coated Porous Substrates as a Platform for Mineralized beta-FeOOH
      Nanorods with Photocatalysis under Sunlight.
AB  - Immobilization of photo-Fenton catalysts on porous materials is crucial to the
      efficiency and stability for water purification. Here we report polydopamine
      (PDA)-coated porous substrates as a platform for in situ mineralizing beta-FeOOH
      nanorods with enhanced photocatalytic performance under sunlight. The PDA coating
      plays multiple roles as an adhesive interface, a medium inducing mineral
      generation, and an electron transfer layer. The mineralized beta-FeOOH nanorods
      perfectly wrap various porous substrates and are stable on the substrates that
      have a PDA coating. The immobilized beta-FeOOH nanorods have been shown to be
      efficient for degrading dyes in water via a photo-Fenton reaction. The
      degradation efficiency reaches approximately 100% in 60 min when the reaction was
      carried out with H2O2 under visible light, and it remains higher than 90% after
      five cycles. We demonstrate that the PDA coating promotes electron transfer to
      reduce the electron-hole recombination rate. As a result, the beta-FeOOH nanorods
      wrapped on the PDA-coated substrates show enhanced photocatalytic performance
      under direct sunlight in the presence of H2O2. Moreover, this versatile platform
      using porous materials as the substrate is useful in fabricating beta-FeOOH
      nanorods-based membrane reactor for wastewater treatment. 

PMID- 25969861
TI  - Basal-Plane Functionalization of Chemically Exfoliated Molybdenum Disulfide by
      Diazonium Salts.
AB  - Although transition metal dichalcogenides such as MoS2 have been recognized as
      highly potent two-dimensional nanomaterials, general methods to chemically
      functionalize them are scarce. Herein, we demonstrate a functionalization route
      that results in organic groups bonded to the MoS2 surface via covalent C-S bonds.
      This is based on lithium intercalation, chemical exfoliation and subsequent
      quenching of the negative charges residing on the MoS2 by electrophiles such as
      diazonium salts. Typical degrees of functionalization are 10-20 atom % and are
      potentially tunable by the choice of intercalation conditions. Significantly, no
      further defects are introduced, and annealing at 350  degrees C restores the
      pristine 2H-MoS2. We show that, unlike both chemically exfoliated and pristine
      MoS2, the functionalized MoS2 is very well dispersible in anisole, confirming a
      significant modification of the surface properties by functionalization. DFT
      calculations show that the grafting of the functional group to the sulfur atoms
      of (charged) MoS2 is energetically favorable and that S-C bonds are formed. 

PMID- 25969862
TI  - Diffusion Influenced Adsorption Kinetics.
AB  - When the kinetics of adsorption is influenced by the diffusive flow of solutes,
      the solute concentration at the surface is influenced by the surface coverage of
      solutes, which is given by the Langmuir-Hinshelwood adsorption equation. The
      diffusion equation with the boundary condition given by the Langmuir-Hinshelwood
      adsorption equation leads to the nonlinear integro-differential equation for the
      surface coverage. In this paper, we solved the nonlinear integro-differential
      equation using the Grunwald-Letnikov formula developed to solve fractional
      kinetics. Guided by the numerical results, analytical expressions for the upper
      and lower bounds of the exact numerical results were obtained. The upper and
      lower bounds were close to the exact numerical results in the diffusion- and
      reaction-controlled limits, respectively. We examined the validity of the two
      simple analytical expressions obtained in the diffusion-controlled limit. The
      results were generalized to include the effect of dispersive diffusion. We also
      investigated the effect of molecular rearrangement of anisotropic molecules on
      surface coverage. 

PMID- 25969863
TI  - Haemodialysis in Diabetic Patients Modulates Inflammatory Cytokine Profile and T
      Cell Activation Status.
AB  - Diabetic nephropathy (DN) is a common complication in patients with diabetes, and
      most of them need renal replacement therapy such as haemodialysis (HD). These
      patients have a high tendency to develop infections and exhibit anomalies in the
      immune system. The objective of this study was to assess the expression of
      activation-related markers on T cells, as well as to quantify inflammatory
      cytokines, before and after a single HD session in DN patients. The study
      involved DN patients under HD treatment who signed an informed consent form.
      Blood samples before and after one HD session were collected, to analyse the
      expression of CD25, CD69 and CD71 in T cells. We also quantified IL-12p70, IL-8,
      IL-10, IL-1beta, TNF-alpha and IL-6 in serum samples using the cytometric bead
      array technique. After the HD session, there was an increase in the CD4/CD8 ratio
      due to significant alterations in both subsets. The relative percentage of CD25+
      cells and CD8+ CD25+ increased significantly after the HD session, while the
      relative percentage of CD69 T cells decreased. There was a significant decrease
      in the CD25 mean fluorescence intensity values for CD4+ T, as well as in the case
      of CD71 in T cells after the HD session. Regarding cytokine synthesis, we found a
      significant increase in IL-10 and IL-6 and a decrease in IL-8 after HD session.
      This study showed that a HD session in DN patients affects the T cell activation
      status in the two major subpopulations and differentially modulates the
      production of inflammatory cytokines. 

PMID- 25969864
TI  - Does the Upper-Limb Work Instability Scale Predict Transitions Out of Work Among
      Injured Workers?
AB  - OBJECTIVE: To investigate the predictive ability of the Upper-Limb Work
      Instability Scale (UL-WIS) for transitioning out of work among injured workers
      with chronic, work-related upper extremity disorders (WRUEDs). DESIGN: Secondary
      analysis of a 12-month cohort study with data collection at baseline and 3-, 6-,
      and 12-month follow-up. Survey questionnaires were used to collect data on an
      array of sociodemographic, health-related, and work-related variables. SETTING:
      Upper extremity specialty clinics. PARTICIPANTS: Injured workers (N=356) with
      WRUEDs who were working at the time of initial clinic attendance. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURE: Transitioning out of work. RESULTS:
      Multivariable logistic regression that considered 9 potential confounders
      revealed baseline UL-WIS (range, 0-17) to be a statistically significant
      predictor of a subsequent transition out of work (adjusted odds ratio, 1.18; 95%
      confidence interval [CI], 1.07-1.31; P=.001). An assessment of predictive values
      across the UL-WIS score range identified cut-scores of <6 (negative predictive
      value, .81; 95% CI, .62-.94) and >15 (positive predictive value, .80; 95% CI, .52
      .96), differentiating the scale into 3 bands representing low, moderate, and high
      risk of exiting work. CONCLUSIONS: The UL-WIS was shown to be an independent
      predictor of poor work sustainability among injured workers with chronic WRUEDs;
      however, when applied as a standalone tool in clinical settings, some limits to
      its predictive accuracy should also be recognized.

PMID- 25969865
TI  - Feasibility and Safety of Cardiopulmonary Exercise Testing in Multiple Sclerosis:
      A Systematic Review.
AB  - OBJECTIVE: To investigate the feasibility and safety of cardiopulmonary exercise
      testing (CPET) in patients with multiple sclerosis (MS). DATA SOURCES: PubMed,
      EMBASE, CINAHL, SPORTDiscus, PsycINFO, ERIC, and the Psychology and Behavioral
      Sciences Collection were searched up to October 2014. References from retrieved
      articles were examined to identify additional relevant studies. STUDY SELECTION:
      Inclusion of original studies was on the basis of performance of maximal CPET,
      description of the protocol, and participants with definite MS aged >=18 years.
      No language restrictions were applied. DATA EXTRACTION: The quality of CPET
      reporting in included studies was scored according to a structured checklist
      considering 10 feasibility (eg, test abnormalities) and 12 safety quality
      criteria (eg, adverse events). Structured data extraction was performed for these
      feasibility and safety features of CPET. DATA SYNTHESIS: Forty-six studies were
      included, comprising 1483 patients with MS, with a mean age +/- SD of 42.0+/-5.8
      years and a median Expanded Disability Status Scale (EDSS) score of 2.8 (first
      quartile=2.1; third quartile=3.9; range of average EDSS scores, .75-5.8). Quality
      of reporting on CPET varied from 3 to 13 out of a possible 22 quality points. The
      percentage of test abnormalities (feasibility) was 10.0%, primarily because of an
      inability to maintain pedaling at a specific resistance. The percentage of
      adverse events (safety) was 2.1%. All adverse events were temporary. CONCLUSIONS:
      Based on the available data, we conclude that CPET is feasible provided that the
      CPET modality is tailored to the physical abilities of the patient. Furthermore,
      CPET is safe when recommended precautions and safety measures are implemented.
      However, future optimization of CPET will require protocolized testing and the
      implementation of standard reporting procedures.

PMID- 25969866
TI  - Low-dose methotrexate may preserve a stronger antileukemic effect than that of
      cyclosporine after modified donor lymphocyte infusion in unmanipulated
      haploidentical HSCT.
AB  - To compare the impacts of low-dose methotrexate (MTX) with cyclosporine (CSA) on
      graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after
      haploidentical modified donor lymphocyte infusion (DLI). Fifty-five consecutive
      patients who had relapsed acute leukemia after haploidentical hematopoietic stem
      cell transplantation (HSCT) and received modified DLI were retrospectively
      studied. Forty-one patients received CSA and 14 received low-dose MTX after DLI
      to prevent DLI-associated GVHD. The incidence of acute GVHD and grade 2-4 acute
      GVHD in MTX group showed a trend toward being higher than in CSA group (61.0% vs.
      37.3%, p = 0.198 and 61.0% vs. 35.5%, p = 0.155). However, no significant
      difference in the incidence of grade 3-4 acute GVHD between two groups (p =
      0.982) was observed. Moreover, compared with CSA, patients treated with MTX had
      lower re-relapse rate (38.1% vs. 80.8%, p = 0.029), better disease-free survival
      (DFS) (51.9% vs. 15.6%, p = 0.06), and higher absolute lymphocyte counts at 30,
      45, 60, and 90 d after modified DLI (p < 0.05). This study suggested that after
      haploidentical modified DLI, low-dose MTX is at least as effective as CSA in the
      prevention of DLI-associated GVHD and probably allowed stronger GVL effect than
      CSA. This phenomenon was probably due to a direct antitumor effect and a better
      reconstitution of lymphocytes after modified DLI induced by low-dose MTX.

PMID- 25969867
TI  - A dual two dimensional electronic portal imaging device transit dosimetry model
      based on an empirical quadratic formalism.
AB  - OBJECTIVE: This study describes a two dimensional electronic portal imaging
      device (EPID) transit dosimetry model that can predict either: (1) in-phantom
      exit dose, or (2) EPID transit dose, for treatment verification. METHODS: The
      model was based on a quadratic equation that relates the reduction in intensity
      to the equivalent path length (EPL) of the attenuator. In this study, two sets of
      quadratic equation coefficients were derived from calibration dose planes
      measured with EPID and ionization chamber in water under reference conditions.
      With two sets of coefficients, EPL can be calculated from either EPID or
      treatment planning system (TPS) dose planes. Consequently, either the in-phantom
      exit dose or the EPID transit dose can be predicted from the EPL. The model was
      tested with two open, five wedge and seven sliding window prostate and head and
      neck intensity-modulated radiation therapy (IMRT) fields on phantoms. Results
      were analysed using absolute gamma analysis (3%/3 mm). RESULTS: The open fields
      gamma pass rates were >96.8% for all comparisons. For wedge and IMRT fields,
      comparisons between predicted and TPS-computed in-phantom exit dose resulted in
      mean gamma pass rate of 97.4% (range, 92.3-100%). As for the comparisons between
      predicted and measured EPID transit dose, the mean gamma pass rate was 97.5%
      (range, 92.6-100%). CONCLUSION: An EPID transit dosimetry model that can predict
      in-phantom exit dose and EPID transit dose was described and proven to be valid.
      ADVANCES IN KNOWLEDGE: The described model is practical, generic and flexible to
      encourage widespread implementation of EPID dosimetry for the improvement of
      patients' safety in radiotherapy.

PMID- 25969869
TI  - The evolution of an annual life cycle in killifish: adaptation to ephemeral
      aquatic environments through embryonic diapause.
AB  - An annual life cycle is characterized by growth, maturity, and reproduction
      condensed into a single, short season favourable to development, with production
      of embryos (seeds, cysts, or eggs) capable of surviving harsh conditions which
      juveniles or adults cannot tolerate. More typically associated with plants in
      desert environments, or temperate-zone insects exposed to freezing winters, the
      evolution of an annual life cycle in vertebrates is fairly novel. Killifish,
      small sexually dimorphic fishes in the Order Cyprinodontiformes, have adapted to
      seasonally ephemeral water bodies across much of Africa and South America through
      the independent evolution of an annual life history. These annual killifish
      produce hardy desiccation-resistant eggs that undergo diapause (developmental
      arrest) and remain buried in the soil for long periods when fish have perished
      due to the drying of their habitat. Killifish are found in aquatic habitats that
      span a continuum from permanent and stable to seasonal and variable, thus
      providing a useful system in which to piece together the evolutionary history of
      this life cycle using natural comparative variation. I first review adaptations
      for life in ephemeral aquatic environments in killifish, with particular emphasis
      on the evolution of embryonic diapause. I then bring together available evidence
      from a variety of approaches and provide a scenario for how this annual life
      cycle evolved. There are a number of features within Aplocheiloidei killifish
      including their inhabitation of marginal or edge aquatic habitat, their small
      size and rapid attainment of maturity, and egg properties that make them
      particularly well suited to the colonization of ephemeral waters. 

PMID- 25969870
TI  - Cognitive testing with the Post-Operative Quality of Recovery Scale in pre
      surgery cancer patients--a controlled study.
AB  - BACKGROUND: Post-Operative Quality of Recovery Scale (PQRS) has been revised to
      allow for the normal variation in cognitive performance seen in healthy
      volunteers. This modification could result in exclusion of test subjects because
      of poor baseline performance. Our aim was to investigate the impact of severe
      disease and waiting for cancer surgery on PQRS baseline cognitive performance and
      exclusion rate, and also on variation in cognitive performance at test re-test.
      METHODS: Sixty-one subjects, 31 women diagnosed with breast cancer and waiting
      for surgery and 30 healthy women, performed the PQRS cognitive, nociceptive and
      emotional domains three times in 48 h. Exclusion rate, change in score and the
      proportion fulfilling 'recovery' criteria at re-tests were assessed. RESULTS:
      Nine out of 31 patients (29%) and two out of 30 controls (7%) had too low
      baseline score to be further assessed (P = 0.043). The change in score at re
      tests was similar between the groups. Sixty-four per cent and 83% at 20 h and 79%
      and 86% at 48 h in the patient and control groups respectively fulfilled the
      'recovery' criteria (P = 0.45). The 'recovery' for nociceptive and emotional
      distress was similar between the groups, but anxiety and sadness absolute scores
      were significantly higher in the patient group. CONCLUSION: Women with breast
      cancer waiting for surgery expressed a higher level of emotional distress,
      performed lower at baseline but showed no difference in test re-test variability
      in cognitive performance according to the PQRS when compared with controls. The
      considerable exclusion rate among patients waiting for cancer surgery should be
      acknowledged.

PMID- 25969868
TI  - Applications of nanoparticles for diagnosis and therapy of cancer.
AB  - During the last decades, a plethora of nanoparticles have been developed and
      evaluated and a real hype has been created around their potential application as
      diagnostic and therapeutic agents. Despite their suggestion as potential
      diagnostic agents, only a single diagnostic nanoparticle formulation, namely iron
      oxide nanoparticles, has found its way into clinical routine so far. This fact is
      primarily due to difficulties in achieving appropriate pharmacokinetic properties
      and a reproducible synthesis of monodispersed nanoparticles. Furthermore,
      concerns exist about their biodegradation, elimination and toxicity. The majority
      of nanoparticle formulations that are currently routinely used in the clinic are
      used for therapeutic purposes. These therapeutic nanoparticles aim to more
      efficiently deliver a (chemo-) therapeutic drug to the pathological site, while
      avoiding its accumulation in healthy organs and tissues, and are predominantly
      based on the "enhanced permeability and retention" (EPR) effect. Furthermore,
      based on their ability to integrate diagnostic and therapeutic entities within a
      single nanoparticle formulation, nanoparticles hold great promise for theranostic
      purposes and are considered to be highly useful for personalizing nanomedicine
      based treatments. In this review article, we present applications of diagnostic
      and therapeutic nanoparticles, summarize frequently used non-invasive imaging
      techniques and describe the role of EPR in the accumulation of nanotheranostic
      formulations. In this context, the clinical potential of nanotheranostics and
      image-guided drug delivery for individualized and improved (chemo-) therapeutic
      interventions is addressed. 

PMID- 25969872
TI  - Technology is no substitute for nursing judgment.

PMID- 25969871
TI  - Epidemiology and clinical evolution of non-melanoma skin cancer in renal
      transplant recipients: a single-center experience in Sao Paulo, Brazil.
AB  - BACKGROUND: Non-melanoma skin cancer (NMSC) is very common among renal transplant
      recipients (RTRs) as a result of the immunosuppressed status of these patients
      and other factors. Few studies have examined the clinical characteristics and
      evolution of NMSC in RTRs in tropical countries. OBJECTIVES: The aim of this
      study was to characterize the epidemiology and clinical evolution of NMSC in
      RTRs. METHODS: We conducted a retrospective study including 68 RTRs with NMSC
      diagnosed from July 2004 to December 2009 with a minimum follow-up of three
      years. We analyzed demographic and transplant- and NMSC-related data. RESULTS:
      The mean age of patients at the first diagnosis of NMSC was 51 years (range: 29
      71 years). Most first diagnoses occurred within nine years post-transplant. The
      majority of patients (n = 48) had Fitzpatrick skin phototype II, although NMSC
      was also observed in those with skin phototypes III and IV. Forty-six (67.6%)
      RTRs had received a kidney from a living donor. Fifty-five (80.9%) RTRs had
      received cytotoxic immunosuppressives, 51 (75.0%) had received calcineurin
      inhibitors, and two (2.9%) had received mTOR inhibitors. Most of the RTRs
      developed about eight NMSC lesions, but up to 25 NMSC lesions were diagnosed in
      one patient. Most lesions (67.6%) were located on sun-exposed areas. Squamous
      cell carcinoma (SCC) represented the predominant tumor type, accounting for 70.6%
      of all tumors, whereas basal cell carcinoma accounted for 29.4% of all tumors.
      Invasive SCC predominated over in situ SCC. Finally, 48.5% of patients had a
      previous history of viral warts. CONCLUSIONS: Long-term use of immunosuppressive
      therapy increases the risk for tumor occurrence. Multiple NMSC tumors can develop
      in patients in tropical countries, even in patients with a high skin phototype.
      Therefore, RTRs should understand the high risk for the development of malignant
      tumors and should be properly informed about the prevention and treatment of
      NMSC.

PMID- 25969875
TI  - Moral courage: A step beyond patient advocacy.

PMID- 25969876
TI  - The inside beat on cardiac tamponade due to lead perforation.

PMID- 25969877
TI  - Hypoglycemia prevention: An innovative approach.

PMID- 25969878
TI  - Is an online BSN degree in your future?

PMID- 25969879
TI  - Paying it forward.

PMID- 25969883
TI  - The pink lady.

PMID- 25969884
TI  - Varicose veins.

PMID- 25969885
TI  - How an aging population is transforming nursing.

PMID- 25969886
TI  - Taking a closer look at pediculosis capitis.

PMID- 25969887
TI  - Fundamentals: Still the building blocks of safe patient care.

PMID- 25969888
TI  - Tune into safety for hearing-impaired patients.

PMID- 25969889
TI  - Drugs for urologic disorders.

PMID- 25969890
TI  - Endometriosis resources.

PMID- 25969893
TI  - Animal models of surgically manipulated flow velocities to study shear stress
      induced atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease of the arterial tree that
      develops at predisposed sites, coinciding with locations that are exposed to low
      or oscillating shear stress. Manipulating flow velocity, and concomitantly shear
      stress, has proven adequate to promote endothelial activation and subsequent
      plaque formation in animals. In this article, we will give an overview of the
      animal models that have been designed to study the causal relationship between
      shear stress and atherosclerosis by surgically manipulating blood flow velocity
      profiles. These surgically manipulated models include arteriovenous fistulas,
      vascular grafts, arterial ligation, and perivascular devices. We review these
      models of manipulated blood flow velocity from an engineering and biological
      perspective, focusing on the shear stress profiles they induce and the vascular
      pathology that is observed. 

PMID- 25969892
TI  - Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic
      microspheres and apolipoprotein A-I plasmids.
AB  - BACKGROUND: Low levels of HDL-C are an independent cardiovascular risk factor
      associated with increased premature cardiovascular death. However, HDL-C
      therapies historically have been limited by issues relating to immunogenicity,
      hepatotoxicity and scalability, and have been ineffective in clinical trials.
      OBJECTIVE: We examined the feasibility of using injectable acoustic microspheres
      to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify
      increased production of HDL-C in vivo. METHODS: Our novel site-specific gene
      delivery system was examined in naive rat model and comprised the following
      steps: (1) intravenous co-administration of a solution containing acoustically
      active microspheres (OptisonTM, GE Healthcare, Princeton, New Jersey) and human
      ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres
      within the liver vasculature; (3) External application of locally-directed
      acoustic energy, (4) induction of microsphere disruption and in situ
      sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression
      of human ApoA-I protein; and (6) elevation of serum HDL-C. RESULTS: Co
      administration of ApoA-I plasmids and acoustic microspheres, activated by
      external ultrasound energy, resulted in transcription and production of human
      ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05).
      CONCLUSIONS: HDL-C was increased in rats following ultrasound directed delivery
      of human ApoA-I plasmids by microsphere sonoporation. The present method provides
      a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation,
      potentially permitting the use of a minimally-invasive ultrasound-based, gene
      delivery system for treating individuals with low HDL-C.

PMID- 25969894
TI  - Immunogenicity and safety of investigational vaccine formulations against
      meningococcal serogroups A, B, C, W, and Y in healthy adolescents.
AB  - This phase 2 study assessed the immunogenicity, safety, and reactogenicity of
      investigational formulations of meningococcal ABCWY vaccines, consisting of
      recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a
      licensed serogroup B vaccine, combined with components of a licensed quadrivalent
      meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy
      adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one
      of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY
      CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo.
      Immunogenicity was assessed by serum bactericidal assay with human complement
      (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions
      and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited
      robust ACWY immune responses, with higher seroresponse rates than one dose of
      MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV
      components were highest in subjects who received 2 doses of OMV-containing
      MenABCWY formulations, with >=68% of subjects achieving hSBA titers >=5 against
      each of the serogroup B test strains. After the first dose, solicited local
      reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM
      group, but similar across groups after the second dose, consisting mainly of
      transient injection site pain. Fever (>=38.0 degrees C) was rare and there were
      no vaccine-related serious AEs. In conclusion, investigational MenABCWY
      formulations containing OMV components elicited highly immunogenic responses
      against meningococcal serogroups ACWY, as well as serogroup B test strains, with
      an acceptable safety profile. [NCT01210885]. 

PMID- 25969895
TI  - Caffeine-induced increase in voluntary activation and strength of the quadriceps
      muscle during isometric, concentric and eccentric contractions.
AB  - This study investigated effects of caffeine ingestion (8 mg/kg) on maximum
      voluntary torque (MVT) and voluntary activation of the quadriceps during
      isometric, concentric and eccentric contractions. Fourteen subjects ingested
      caffeine and placebo in a randomized, controlled, counterbalanced, double-blind
      crossover design. Neuromuscular tests were performed before and 1 h after oral
      caffeine and placebo intake. MVTs were measured and the interpolated twitch
      technique was applied during isometric, concentric and eccentric contractions to
      assess voluntary activation. Furthermore, normalized root mean square of the EMG
      signal was calculated and evoked spinal reflex responses (H-reflex evoked at rest
      and during weak isometric voluntary contraction) as well as twitch torques were
      analyzed. Caffeine increased MVT by 26.4 N m (95%CI: 9.3-43.5 N m, P = 0.004),
      22.5 N m (95%CI: 3.1-42.0 N m, P = 0.025) and 22.5 N m (95%CI: 2.2-42.7 N m, P =
      0.032) for isometric, concentric and eccentric contractions. Strength
      enhancements were associated with increases in voluntary activation. Explosive
      voluntary strength and voluntary activation at the onset of contraction were
      significantly increased following caffeine ingestion. Changes in spinal reflex
      responses and at the muscle level were not observed. Data suggest that caffeine
      ingestion induced an acute increase in voluntary activation that was responsible
      for the increased strength regardless of the contraction mode.

PMID- 25969896
TI  - Chapter 3: The model for assessment of telemedicine (MAST) - evaluation of
      telemedical solutions.

PMID- 25969897
TI  - Chapter 4: Literature review.

PMID- 25969898
TI  - Chapter 5: Barriers and facilitators for eHealth.

PMID- 25969900
TI  - Chapter 7: conclusion.

PMID- 25969899
TI  - Chapter 6: Road map for implementation in clinical practice.

PMID- 25969902
TI  - Executive summary.

PMID- 25969903
TI  - Appendix 1: literature review - search strategy and literature overview.

PMID- 25969905
TI  - Chapter 2: terminology.

PMID- 25969904
TI  - Chapter 1: Background and aim of the document.

PMID- 25969906
TI  - History of venereal diseases from antiquity to the renaissance.
AB  - Sexually transmitted diseases (STDs), previously known as venereal diseases (VD),
      were present among the populations of antiquity as well as during the Middle
      Ages. Clay tablets from Mesopotamia, Egyptian papyri, along with mythology,
      paintings of erotic scenes, and presence of prostitutes give sufficient
      information to assume that some form of urethral and vaginal discharge, and also
      herpes genitalis were present among people at that time, and that these diseases
      were considered a divine punishment. Some passages of the Bible say much about
      the sexual behavior of the ancient Hebrews. The writings of the Greek and Roman
      physicians and of their satiric poets (Martial, Juvenal, Ovid) described diverse
      genital diseases. Celsus described various diseases of the genitals, that he
      called the "obscene parts". Galen made a strange description of the female
      genitals and coined the term gonorrhea - flow of semen. The ancient Chinese and
      Indian physicians also gave some account on the presence of venereal diseases in
      their books, and the temple sculptures depict their sexual life. During the
      Middle Ages, numerous physicians and surgeons from Europe as well as from Arabic
      countries wrote on local diseases of the genitals, describing chancres,
      condylomata, erosions, pustules, urethral and vaginal discharge, and their
      treatment. Some were aware that the alterations were connected with sexual
      activity. In spite the fact the Christian church propagated abstinence, the
      spread of venereal diseases was possible because the diffusion of prostitution,
      communal baths, and wars. During the 19th century, some of the physicians and
      historians, especially J. Rosenbaum, F. Buret, and E. Lancereaux believed
      syphilis was as old as mankind, whereas later authors had the opinion the disease
      appeared at the end of the 15th century.

PMID- 25969907
TI  - In vivo visualization of hair follicles by ultrasound biomicroscopy in alopecia
      areata and its correlation with histopathology.
AB  - Ultrasound biomicroscopy (UBM) is a non-invasive imaging technique used in
      examination of several skin diseases but never in imaging hair and scalp
      diseases. Main objective of this investigation was assessment of the efficacy of
      UBM for in vivo visualization of hair follicles in cases of alopecia areata (AA)
      and correlation of findings with histopathological findings. This study included
      30 patients with AA. Two areas, one with AA and a control area, were marked,
      examined by UBM and then biopsied for histopathological examination. In patients
      with alopecia totalis (AT) or universalis (AU) only an AA area was examined. Non
      echogenic conical shadows reaching the epidermal entrance echo (probably
      corresponding to the hair follicles) were seen and were wider and fewer in number
      in areas of AA than in normal control areas. No significant difference was found
      regarding number and width of hair follicles between UBM and histopathological
      examination. However, a significant increase in length of follicles in
      histopathology was detected, indicating that the UBM image was probably unable to
      reach the deepest part of the follicle. Main limitation of the study is small
      number of cases. No significant difference was found between UBM and histological
      measurements of hair follicle number and width in patients with AA, making UBM a
      useful tool for in vivo visualization of hair follicles.

PMID- 25969908
TI  - Osteopontin: a new facilitating factor in alopecia areata pathogenesis?
AB  - Osteopontin (OPN) is a multifunctional glycophosphoprotein secreted by many cell
      types, including osteoblasts, lymphocites, macrophages, epithelial cells, and
      vascular smooth muscle cells. It has been implicated in many physiological and
      pathological processes, such as cell-mediated immunity, inflammation, cell
      survival, and tumor invasion and metastasis. Osteopontin has multiple emerging
      roles in cutaneous biology and pathology and OPN involvement has been emphasized
      in Th1-mediated diseases such as psoriasis. Alopecia areata (AA) is a form of non
      scarring hair loss affecting anagen stage hair follicles with a multifactorial
      autoimmune pathogenesis characterized by a prevalent Th1 cytokine profile. Given
      the role of osteopontin in Th1-mediated inflammation, we have postulated that OPN
      may be involved in AA pathogenesis. The aim of our study was to investigate
      plasma OPN level in alopecia areata before and after DPCP treatment. Our results
      showed that OPN plasma levels in patients with alopecia areata were higher than
      in healthy controls, but patients achieving complete recovery after DPCP
      treatment did not show a statistically significant reduction of OPN plasma
      levels.

PMID- 25969909
TI  - Pigment protection factor as a predictor of skin photosensitivity--a Polish
      study.
AB  - Assessment of individual photosensitivity by determining the minimal erythema
      dose (MED) is commonly accepted. MED objectively describes a single individual
      response to the irradiation of skin with a particular wavelength (UVB, UVA).
      Pigment protection factor (PPF) is an objective value to measure skin type. The
      aim of the project was to analyze PPF values in the population of Lodz and the
      relationship between PPF, skin phototype, and individual MED. The study was
      conducted on the group of 270 volunteers: 130 men and 140 women, mean age 28.5
      years (OS + 9.66) with either skin phototype II or III, as defined by Fitzpatrick
      Skin Phototype Classification. Phototesting of each volunteer was undertaken with
      an increasing dose series (UVB radiation) on six squares (1*1 cm) on the skin of
      the back. The MED was defined as a perceptible erythema 24 hours later. Starting
      dose was determined by history, physical examination, and phototype ranged from
      0.03-0.07 J/cm2. PPF was measured by a skin reflectance meter UV Optimize 555.
      The mean MED value was 0.15 J/cm2 and the PPF value was 6.15. A positive
      correlation between the MED value and PPF (R=0.38; P<0.001), and a positive
      correlation between phototype and MED and PPF (P< 0.001) were found. Both
      determination of MED and PPF are objective methods of photosensitivity
      assessment, but PPF determination is an easy and non-invasive method.

PMID- 25969910
TI  - Cardiovascular risk factors in patients with chronic plaque psoriasis: a case
      control study on the Brasov County population.
AB  - Many studies have suggested that cardiovascular risk factors seem to be more
      common in patients with psoriasis than in the general population. In this study
      we aimed to determine the prevalence of cardiovascular risk factors in patients
      with chronic plaque psoriasis depending on the severity of disease. We conducted
      a prospective study in Brasov County (Romania) including 142 patients with
      chronic plaque psoriasis and disease duration of at least six months and 167
      controls without psoriasis. The severity of psoriasis was assessed using the
      psoriasis area and severity index (PASI) score. Along with a thorough medical
      history and physical examination, serum lipid profile and fasting plasma glucose
      tests were carried out. The 10-year Framingham risk score (FRS) for general
      cardiovascular disease, which includes age, gender, total cholesterol, HDL
      cholesterol, systolic blood pressure, smoking status, and diabetes mellitus, was
      applied. The severity of chronic plaque psoriasis was mild in 32 patients
      (22.53%) and moderate to severe in 110 patients (77.47%). We found a significant
      higher prevalence of metabolic syndrome in the patient group compared to
      controls. Individual components of metabolic syndrome like waist circumference,
      elevated triglycerides, reduced HDL-C, impaired fasting plasma glucose, and
      arterial hypertension were also more prevalent in patients than in controls. Mean
      triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol levels were
      significantly raised in patients with psoriasis when compared to controls. The 10
      year FRS was significantly higher in patients with psoriasis than in controls
      (8.36+/-5.75 vs. 6.61+/-4.13; P<0.001). FRS was higher in men (P=0.012) and in
      patients older than 50 years (P=0.008). According to the severity of psoriasis,
      FRS increases significantly from mild to moderate-to-severe psoriasis (6.82+/
      4.48 to 8.8+/-6.71; P=0.003). Psoriasis, and especially moderate to severe
      psoriasis, seems to represent a risk factor for cardiovascular disease. Patients
      with psoriasis should be risk-assessed for cardiovascular diseases, and
      comorbidities should be actively managed.

PMID- 25969911
TI  - Evaluation of etiological factors in patients with chronic urticaria.
AB  - In the last few decades, increasing understanding of the pathomechanisms involved
      in chronic urticaria has highlighted the heterogeneity of different subtypes, and
      chronic urticaria is now classified as chronic spontaneous urticaria and
      inducible urticaria. Although many factors are thought to be involved in chronic
      urticaria, the etiology is yet to be clarified. The purpose of this study was to
      investigate etiological factors in patients with chronic urticaria. Five hundred
      patients with chronic urticaria, 351 women and 149 men, were studied for
      etiological factors. The autologous serum skin test was performed on 197
      patients. Provocation testing for physical urticaria was performed on 354
      patients. Patients with acute urticaria were excluded from the study. We
      determined at least one focus of infection that might be involved in the etiology
      of the disease in 18.8% of cases. Patients with infections were treated, and
      symptoms resolved after treatment in six cases (5.3%). Autologous serum skin
      tests were positive in 125 patients (63.5%). Provocation tests for physical
      urticaria were positive in 131 (37%) patients with urticaria. We suggest that
      physical stimuli and autoantibodies play an important role in the
      etiopathogenesis of urticaria.

PMID- 25969912
TI  - High frequency ultrasonography of the skin and its role as an auxillary tool in
      diagnosis of benign and malignant cutaneous tumors--a comparison of two clinical
      cases.
AB  - The number of dermatologic entities that can be studied by ultrasound examination
      (US) of the skin is increasing. Conventional US and high frequency US (HFUS) are
      considered useful additional tools in improving the diagnosis and management of
      common benign and malignant skin tumors. US may help in positive and differential
      diagnosis of primary melanocytic neoplasms and of locoregional spread in melanoma
      patients. US preoperative evaluation of primary melanoma thickness correlates
      with histologically estimated melanoma thickness, and can help determine surgical
      margins and indications for sentinel lymph node biopsy. It is also useful during
      follow-up after surgical treatment for early detection of recurrence or
      metastases. In this case report, we present two cases of skin lesions clinically
      suspicious for malignancy. The first lesion was a round nodule 3 mm in diameter,
      resembling a blue nevus. In HFUS it was well delimited, hypoechoic, and well
      vascularized. The second lesion presented as an elevated, well-circumscribed
      nodule, 5-6 mm in diameter, inhomogeneous in color. HFUS depicted a poorly
      delimited, irregular, hypoechoic lesion crossing the dermoepidermal junction. At
      the first exam it was not vascularized, but 6 months later a number of vascular
      flow signals within the lesion were found. In histopathological examination the
      lesions were finally diagnosed as, respectively: benign cavernous hemangioma and
      melanoma. In both presented cases HFUS proved to be useful in a differential
      diagnosis of suspicious skin lesions. Noninvasive and easy to perform, HFUS is a
      valuable diagnostic method in dermatology.

PMID- 25969913
TI  - Unilateral eyelid involvement as single presentation of discoid lupus
      erythematosus: a clinical conundrum.
AB  - We report a case of a 30-year-old woman with discoid lupus erythematosus (DLE)
      involving only a single lower eyelid. The diagnostic delay is explained by the
      unspecific clinical and histopathology picture and lack of specific changes in
      the first biopsy specimen taken. The diagnosis was based on later histological
      and immunological studies. Palpebral involvement has rarely been reported as the
      first and sole manifestation of the disease.

PMID- 25969915
TI  - Hypercalciuria in a child with acral peeling skin syndrome: a case report.
AB  - We present a case of 3-year-old Caucasian boy who developed monthly cyclic
      attacks of skin peeling of the palms and soles over 1.5 years. The skin peeling
      was associated with hypercalciuria. No mutation was present in TGM5 and CSTA
      genes, but the typical clinical picture and the biopsy from flaccid blisters on
      the feet confirmed the acral peeling skin syndrome (APSS). The possible
      associations of rare genetic disorders and metabolic conditions in the course of
      APSS need to be investigated. 

PMID- 25969914
TI  - Using photodynamic therapy to estimate effectiveness of innovative combined
      diclofenac and tazaroten therapy of disseminated actinic keratosis.
AB  - Early diagnosis and therapy of precancerous lesions and malignant tumors belong
      to the most challenging tasks in modern medicine. Photodynamic diagnosis can help
      diagnose both precancerous lesions and early carcinoma. Actinic keratosis (AK) is
      the most common precancerous lesion of the skin. The available data show a high
      effectiveness of diclofenac in treating multifocal AK. We report a case of a 52
      year-old woman who complained of multiple disseminated AK lesions predominantly
      on the lower limbs and trunk with a significant exacerbation within the last 6
      months. Due to the spreading of disease and a high number of AK foci, as well as
      technical problems with visiting the hospital (PDT Laboratory), photodynamic
      therapy was not applied. The patient was treated for 2 months with a combination
      of local administration of 3% diclofenac and 0.1% tazaroten and 3% diclofenac
      only as a half side (left-right) comparison. The effects of therapy were later
      clinically evaluated and verified by means of photodynamic diagnosis (PDD)
      directly after therapy and at a follow-up examination 3 months later. The
      evaluation of treatment was blinded. Treatment with diclofenac only on the right
      side of the body resulted in clearing of 55% of all treated lesions, which
      increased to 60% three months after finishing therapy. On the left side of the
      body, where combined therapy (diclofenac 2 times daily on uneven dates and
      diclofenac once a day + tazaroten once a day on even dates) was used, 77.5%
      pathologic lesions disappeared, but this did not increase at follow up. The
      treatment of multifocal, disseminated AK is a difficult task and also burdensome
      for the patient due to side effects like scarring or burning and itching which
      occur during most therapies. Combined therapy with diclofenac and tazaroten
      supported by PDD may improve the effects of routine treatment of AK.

PMID- 25969916
TI  - Efficacy of narrowband UVB phototherapy in erythema dyschromicum perstans
      treatment: case reports.

PMID- 25969917
TI  - Basal cell carcinoma at the University Dermatovenerological Clinic of Ljubljana,
      Slovenia.

PMID- 25969918
TI  - Syphilitic hepatitis: rare or just unrecognized?

PMID- 25969919
TI  - A case of malum perforans pedis complicated by chronic osteomyelitis.

PMID- 25969920
TI  - In memoriam: Stefanija Puretic (1922 - 2015).

PMID- 25969921
TI  - 2H-CuScO2 Prepared by Low-Temperature Hydrothermal Methods and Post-Annealing
      Effects on Optical and Photoelectrochemical Properties.
AB  - The delafossite structured CuScO2 is a p-type, wide band gap oxide that has been
      shown to support significant oxygen intercalation, leading to darkened color and
      increased conductivity. Control of this oxidation proves difficult by the
      conventional high-temperature solid-state syntheses. In addition, a pure
      hexagonal (2H) or rhombohedral (3R) polytype of CuScO2 requires careful control
      of synthetic parameters or intentional doping. Lower-temperature hydrothermal
      syntheses have thus far led to only a mixed 2H/3R product. Herein, control of
      hydrothermal conditions with the consideration of copper and scandium hydrolysis
      led to the synthesis of light beige, hierarchically structured particles of 2H
      CuScO2. Absorption of the particles in the visible range was found to increase
      upon annealing of the sample in air, most likely due to the Cu(II) formation from
      oxygen interstitials. X-ray photoelectron spectroscopy confirmed purely Cu(I) in
      the as-synthesized 2H-CuScO2 and increased Cu(II) amounts upon annealing.
      Oxidation of the samples also led to shifts of the Fermi level toward the valence
      band as observed by increases in the measured flat band potentials versus normal
      hydrogen electrode, confirming increased hole carrier densities. 

PMID- 25969922
TI  - Specificity data for the b Test, Dot Counting Test, Rey-15 Item Plus Recognition,
      and Rey Word Recognition Test in monolingual Spanish-speakers.
AB  - The current study provides specificity data on a large sample (n = 115) of young
      to middle-aged, male, monolingual Spanish speakers of lower educational level and
      low acculturation to mainstream US culture for four neurocognitive performance
      validity tests (PVTs): the Dot Counting, the b Test, Rey Word Recognition, and
      Rey 15-Item Plus Recognition. Individuals with 0 to 6 years of education
      performed more poorly than did participants with 7 to 10 years of education on
      several Rey 15-Item scores (combination equation, recall intrusion errors, and
      recognition false positives), Rey Word Recognition total correct, and E-score and
      omission errors on the b Test, but no effect of educational level was observed
      for Dot Counting Test scores. Cutoff scores are provided that maintain
      approximately 90% specificity for the education subgroups separately. Some of
      these cutoffs match, or are even more stringent than, those recommended for use
      in US test takers who are primarily Caucasian, are tested in English, and have a
      higher educational level (i.e., Rey Word Recognition correct false-positive
      errors; Rey 15-Item recall intrusions and recognition false-positive errors; b
      Test total time; and Dot Counting E-score and grouped dot counting time). Thus,
      performance on these PVT variables in particular appears relatively robust to
      cultural/language/educational factors. 

PMID- 25969923
TI  - Sensitive and direct electrochemical detection of double-stranded DNA utilizing
      alkaline phosphatase-labelled zinc finger proteins.
AB  - Direct detection of double-stranded DNA (dsDNA) using zinc finger proteins (ZFPs)
      is of great importance in biomedical applications such as identifying pathogens
      and circulating DNAs. However, its sensitivity is still not sufficiently high
      because limited signalling labels can be conjugated or fused. Herein, we report
      sensitive and direct detection of dsDNA using (i) alkaline phosphatase (ALP) as a
      fast catalytic label conjugated to ZFPs along with (ii) electrochemical
      measurement of an ALP product (l-ascorbic acid) at the indium-tin oxide electrode
      with a high signal-to-background ratio. ALP is simply conjugated to a ZFP through
      lysine residues in a ZFP purification tag, a maltose binding protein (MBP).
      Sandwich-type electrochemical detection of dsDNA allows a detection limit of ca.
      100 fM without using DNA amplification. 

PMID- 25969924
TI  - Sex-Specific Predictors of Metabolic Syndrome Independent of Its Components.
AB  - To what extent is the metabolic syndrome (MetS) determined beyond its recognized
      components? In 1702, middle-aged men and women without MetS at baseline, MetS
      development was identified in 546 participants at a mean of 10.1-year follow-up.
      Participants subsequently developing MetS had, beyond higher values of MetS
      traits, significantly higher total and low-density lipoprotein cholesterol,
      apolipoprotein B, C-reactive protein (CRP), gamma-glutamyl transferase (GGT), and
      lower high-density lipoprotein cholesterol. Females were significantly more
      frequent never smokers and males had lower values of total testosterone. In
      logistic regression analyses, adjusted for sex, age, and smoking status, MetS was
      predicted disparately in the sexes, whereas males exhibited, beyond abdominal
      obesity, CRP, GGT, and sex hormone-binding globulin (SHBG) as independent
      predictors, abdominal obesity was not an independent predictor in females in whom
      other than age, CRP conferred MetS risk, whereas SHBG was and current smoking
      tended to be protective. A surrogate of hepatic steatosis proved a major mediator
      of abdominal obesity in determining incident MetS (relative risk, 5.6 [95%
      confidence interval, 3.4-9.3]) in each sex. We confirm that GGT and SHBG are
      novel independent MetS determinants. Hepatic steatosis is the major predictor of
      MetS mediating adiposity in each sex. Abdominal obesity is not an independent
      determinant in Turkish women in whom autoimmune activation seems to prevail
      before MetS development. 

PMID- 25969925
TI  - Quantifying landscape-level methane fluxes in subarctic Finland using a
      multiscale approach.
AB  - Quantifying landscape-scale methane (CH4 ) fluxes from boreal and arctic regions,
      and determining how they are controlled, is critical for predicting the magnitude
      of any CH4 emission feedback to climate change. Furthermore, there remains
      uncertainty regarding the relative importance of small areas of strong
      methanogenic activity, vs. larger areas with net CH4 uptake, in controlling
      landscape-level fluxes. We measured CH4 fluxes from multiple microtopographical
      subunits (sedge-dominated lawns, interhummocks and hummocks) within an aapa mire
      in subarctic Finland, as well as in drier ecosystems present in the wider
      landscape, lichen heath and mountain birch forest. An intercomparison was carried
      out between fluxes measured using static chambers, up-scaled using a high
      resolution landcover map derived from aerial photography and eddy covariance.
      Strong agreement was observed between the two methodologies, with emission rates
      greatest in lawns. CH4 fluxes from lawns were strongly related to seasonal
      fluctuations in temperature, but their floating nature meant that water-table
      depth was not a key factor in controlling CH4 release. In contrast, chamber
      measurements identified net CH4 uptake in birch forest soils. An intercomparison
      between the aerial photography and satellite remote sensing demonstrated that
      quantifying the distribution of the key CH4 emitting and consuming plant
      communities was possible from satellite, allowing fluxes to be scaled up to a 100
      km(2) area. For the full growing season (May to October), ~ 1.1-1.4 g CH4  m(-2)
      was released across the 100 km(2) area. This was based on up-scaled lawn
      emissions of 1.2-1.5 g CH4  m(-2) , vs. an up-scaled uptake of 0.07-0.15 g CH4 
      m(-2) by the wider landscape. Given the strong temperature sensitivity of the
      dominant lawn fluxes, and the fact that lawns are unlikely to dry out, climate
      warming may substantially increase CH4 emissions in northern Finland, and in aapa
      mire regions in general. 

PMID- 25969926
TI  - Local electrical control of magnetic order and orientation by ferroelastic domain
      arrangements just above room temperature.
AB  - Ferroic materials (ferromagnetic, ferroelectric, ferroelastic) usually divide
      into domains with different orientations of their order parameter. Coupling
      between different ferroic systems creates new functionalities, for instance the
      electrical control of macroscopic magnetic properties including magnetization and
      coercive field. Here we show that ferroelastic domains can be used to control
      both magnetic order and magnetization direction at the nanoscale with a voltage.
      We use element-specific X-ray imaging to map the magnetic domains as a function
      of temperature and voltage in epitaxial FeRh on ferroelastic BaTiO3. Exploiting
      the nanoscale phase-separation of FeRh, we locally interconvert between
      ferromagnetic and antiferromagnetic states with a small electric field just above
      room temperature. Imaging and ab initio calculations show the antiferromagnetic
      phase of FeRh is favoured by compressive strain on c-oriented BaTiO3 domains, and
      the resultant magnetoelectric coupling is larger and more reversible than
      previously reported from macroscopic measurements. Our results emphasize the
      importance of nanoscale ferroic domain structure and the promise of first-order
      transition materials to achieve enhanced coupling in artificial multiferroics. 

PMID- 25969928
TI  - Selective and divided attention modulates auditory-vocal integration in the
      processing of pitch feedback errors.
AB  - Speakers rapidly adjust their ongoing vocal productions to compensate for errors
      they hear in their auditory feedback. It is currently unclear what role attention
      plays in these vocal compensations. This event-related potential (ERP) study
      examined the influence of selective and divided attention on the vocal and
      cortical responses to pitch errors heard in auditory feedback regarding ongoing
      vocalisations. During the production of a sustained vowel, participants briefly
      heard their vocal pitch shifted up two semitones while they actively attended to
      auditory or visual events (selective attention), or both auditory and visual
      events (divided attention), or were not told to attend to either modality
      (control condition). The behavioral results showed that attending to the pitch
      perturbations elicited larger vocal compensations than attending to the visual
      stimuli. Moreover, ERPs were likewise sensitive to the attentional manipulations:
      P2 responses to pitch perturbations were larger when participants attended to the
      auditory stimuli compared to when they attended to the visual stimuli, and
      compared to when they were not explicitly told to attend to either the visual or
      auditory stimuli. By contrast, dividing attention between the auditory and visual
      modalities caused suppressed P2 responses relative to all the other conditions
      and caused enhanced N1 responses relative to the control condition. These
      findings provide strong evidence for the influence of attention on the mechanisms
      underlying the auditory-vocal integration in the processing of pitch feedback
      errors. In addition, selective attention and divided attention appear to modulate
      the neurobehavioral processing of pitch feedback errors in different ways. 

PMID- 25969929
TI  - Cardiac sarcoidosis.

PMID- 25969930
TI  - Cardiac sarcoidosis: the challenge of radiologic-pathologic correlation: from the
      radiologic pathology archives.
AB  - Cardiac sarcoidosis is a rare but potentially fatal disorder with a nonspecific
      spectrum of clinical manifestations, including conduction disorders, congestive
      heart failure, ventricular arrhythmias, and sudden cardiac death. Although early
      treatment to improve morbidity and mortality is desirable, sensitive and accurate
      detection of cardiac sarcoidosis remains a challenge. Except for the
      histopathologic finding of noncaseating granulomas in an endomyocardial biopsy
      specimen, most diagnostic tests are limited and nonspecific at best. Therefore,
      the decision to initiate treatment is based largely on the patient's clinical
      symptoms and the course of the disease, rather than histologic confirmation.
      Successful recognition of cardiac sarcoidosis ultimately requires rigorous
      collaboration among a clinician, radiologist, and pathologist. Advanced imaging
      modalities, such as cardiac magnetic resonance imaging and positron emission
      tomography with fluorodeoxyglucose, have become increasingly useful in
      facilitating diagnosis and therapeutic monitoring, although limited prospective
      studies exist. This article describes the clinical parameters and pathologic
      findings of cardiac sarcoidosis and the advanced imaging features and
      differential diagnostic challenges that must be considered for a successful
      diagnostic approach. In addition, to improve the understanding of abnormalities
      detected with different imaging modalities, we suggest a unified terminology in
      describing radiologic findings related to cardiac sarcoidosis.

PMID- 25969927
TI  - Environmentally co-occurring mercury resistance plasmids are genetically and
      phenotypically diverse and confer variable context-dependent fitness effects.
AB  - Plasmids are important mobile elements that can facilitate genetic exchange and
      local adaptation within microbial communities. We compared the sequences of four
      co-occurring pQBR family environmental mercury resistance plasmids and measured
      their effects on competitive fitness of a Pseudomonas fluorescens SBW25 host,
      which was isolated at the same field site. Fitness effects of carriage differed
      between plasmids and were strongly context dependent, varying with medium,
      plasmid status of competitor and levels of environmental mercury. The plasmids
      also varied widely in their rates of conjugation and segregational loss. We found
      that few of the plasmid-borne accessory genes could be ascribed functions,
      although we identified a putative chemotaxis operon, a type IV pilus-encoding
      cluster and a region encoding putative arylsulfatase enzymes, which were
      conserved across geographically distant isolates. One plasmid, pQBR55, conferred
      the ability to catabolize sucrose. Transposons, including the mercury resistance
      Tn5042, appeared to have been acquired by different pQBR plasmids by
      recombination, indicating an important role for horizontal gene transfer in the
      recent evolution of pQBR plasmids. Our findings demonstrate extensive genetic and
      phenotypic diversity among co-occurring members of a plasmid community and
      suggest a role for environmental heterogeneity in the maintenance of plasmid
      diversity. 

PMID- 25969931
TI  - De-identification of Medical Images with Retention of Scientific Research Value.
AB  - Online public repositories for sharing research data allow investigators to
      validate existing research or perform secondary research without the expense of
      collecting new data. Patient data made publicly available through such
      repositories may constitute a breach of personally identifiable information if
      not properly de-identified. Imaging data are especially at risk because some
      intricacies of the Digital Imaging and Communications in Medicine (DICOM) format
      are not widely understood by researchers. If imaging data still containing
      protected health information (PHI) were released through a public repository, a
      number of different parties could be held liable, including the original
      researcher who collected and submitted the data, the original researcher's
      institution, and the organization managing the repository. To minimize these
      risks through proper de-identification of image data, one must understand what
      PHI exists and where that PHI resides, and one must have the tools to remove PHI
      without compromising the scientific integrity of the data. DICOM public elements
      are defined by the DICOM Standard. Modality vendors use private elements to
      encode acquisition parameters that are not yet defined by the DICOM Standard, or
      the vendor may not have updated an existing software product after DICOM defined
      new public elements. Because private elements are not standardized, a common de
      identification practice is to delete all private elements, removing
      scientifically useful data as well as PHI. Researchers and publishers of imaging
      data can use the tools and process described in this article to de-identify DICOM
      images according to current best practices.

PMID- 25969932
TI  - Understanding bibliometric parameters and analysis.
AB  - Bibliometric parameters have become an important part of modern assessment of
      academic productivity. These parameters exist for the purpose of evaluating
      authors (publication count, citation count, h-index, m-quotient, hc-index, e
      index, g-index, i-10 [i-n] index) and journals (impact factor, Eigenfactor,
      article influence score, SCImago journal rank, source-normalized impact per
      paper). Although in recent years there has been a proliferation of bibliometric
      parameters, the true meaning and appropriate use of these parameters is generally
      not well understood. Effective use of existing and emerging bibliometric tools
      can aid in assessment of academic productivity, including readiness for
      promotions and other awards. However, if not properly understood, the data can be
      misinterpreted and may be subject to manipulation. Familiarity with bibliometric
      parameters will aid in their effective implementation in the review of authors
      whether individuals or groups-and journals, as well as their possible use in the
      promotions review process, maximizing the effectiveness of bibliometric analysis.

PMID- 25969933
TI  - Talar Fractures and Dislocations: A Radiologist's Guide to Timely Diagnosis and
      Classification.
AB  - The talus, the second largest tarsal bone, has distinctive imaging
      characteristics and injury patterns. The predominantly extraosseous vascular
      supply of the talus predisposes it to significant injury in the setting of
      trauma. In addition, the lack of muscular attachments and absence of a secondary
      blood supply can lead to subsequent osteonecrosis. Although talar fractures
      account for less than 1% of all fractures, they commonly result from high-energy
      trauma and may lead to complications and long-term morbidity if not recognized
      and managed appropriately. While initial evaluation is with foot and ankle
      radiographs, computed tomography (CT) is often performed to evaluate the extent
      of the fracture, displacement, comminution, intra-articular extension, and
      associated injuries. Talar fractures are divided by anatomic region: head, neck,
      and body. Talar head fractures can be treated conservatively if nondisplaced,
      warranting careful radiographic and CT evaluation to assess rotation,
      displacement, and extension into the neck. The modified Hawkins-Canale
      classification of talar neck fractures is most commonly used due to its
      simplicity, usefulness in guiding treatment, and prognostic value, as it
      correlates associated malalignment with risk of subsequent osteonecrosis.
      Isolated talar body fractures may be more common than previously thought. The
      Sneppen classification further divides talar body fractures into osteochondral
      talar dome, lateral and posterior process, and shear and crush comminuted central
      body fractures. Crush comminuted central body fractures carry a poor prognosis
      due to nonanatomic reduction, bone loss, and subsequent osteonecrosis. Lateral
      process fractures can be radiographically occult and require a higher index of
      suspicion for successful diagnosis. Subtalar dislocations are often accompanied
      by fractures, necessitating postreduction CT. Familiarity with the unique talar
      anatomy and injury patterns is essential for radiologists to facilitate
      appropriate and timely management.

PMID- 25969934
TI  - Osteoarticular transplantation: recognizing expected postsurgical appearances and
      complications.
AB  - Despite technologic advances in prosthetic joint replacement, young patients who
      have lost a large volume of bone or soft tissue because of a tumor or traumatic
      injury may not be good candidates for prosthetic implants, which have limited
      longevity relative to that of biologic tissue grafts. In recent years, the use of
      biologic materials in orthopedic surgery has increased. Such materials, known as
      allografts, consist of cadaveric bone, cartilage, and other soft tissues that can
      be transplanted into a living patient. Alternatively, osteochondral autografts,
      or autologous grafts of the patient's own bone and/or cartilage, can be harvested
      from one body site and transplanted to another. Surgical procedures range from
      the local implantation of small osteochondral plugs to the replacement of entire
      joints with allografts. The size of the allograft used depends on the amount of
      bone and soft tissue needed. The use of allografts in patients with large-volume
      bone loss often preserves limb function, obviating amputation, which makes it an
      attractive option for treatment of young patients. Advantages of using allografts
      include the similarity of graft materials to native tissues and the decreased
      patient morbidity in the absence of an autograft donor site; disadvantages
      include slower biologic remodeling and graft incorporation than are typical with
      the use of autologous grafts. Potential complications of allograft tissue
      implantation include graft nonunion, collapse, and failure; infection; and
      secondary osteoarthritis. The article discusses the indications for and basic
      steps involved in each type of transplant procedure, normal pre- and
      postoperative imaging appearances, and imaging features that may be indicative of
      transplant complications.

PMID- 25969935
TI  - Glial tumors in brodmann area 6: spread pattern and relationships to motor areas.
AB  - The posterior frontal lobe of the brain houses Brodmann area 4, which is the
      primary motor cortex, and Brodmann area 6, which consists of the supplementary
      motor area on the medial portion of the hemisphere and the premotor cortex on the
      lateral portion. In this area, safe resection is dependent on accurate
      localization of the motor cortex and the central sulcus, which can usually be
      achieved by using thin-section imaging and confirmed by using other techniques.
      The most reliable anatomic landmarks are the "hand knob" area and the marginal
      ramus of the cingulate sulcus. Postoperatively, motor deficits can occur not only
      because of injury to primary motor cortex but also because of injury to the
      supplementary motor area. Unlike motor cortex injury, the supplementary motor
      area syndrome is transient, if it occurs at all. On the lateral hemisphere, motor
      and language deficits can also occur because of premotor cortex injury, but a
      dense motor deficit would indicate subcortical injury to the corticospinal tract.
      The close relationship of the subcortical motor fibers and premotor cortex is
      illustrated. In contrast to the more constant landmarks of the central sulcus and
      marginal ramus, which aid in preoperative localization, the variable
      interruptions in the precentral and cingulate sulci of the posterior frontal lobe
      seem to provide "cortical bridges" for spread of infiltrating gliomas.

PMID- 25969936
TI  - Postsurgical imaging of the oral cavity and oropharynx: what radiologists need to
      know.
AB  - The oral cavity and oropharynx are common locations of neoplastic lesions;
      neoplasms at these sites are often treated with surgery. The goal of this
      surgical treatment is to achieve tumor control while preserving, whenever
      possible, the function of local structures. The procedure used depends largely on
      the location and extension of the tumor and the disease stage. Follow-up
      evaluation of patients is done with computed tomography (CT) and magnetic
      resonance (MR) imaging. The ability to interpret characteristic features at CT
      and MR imaging is particularly important because normal anatomic structures are
      altered in specific patterns according to the distinct surgical technique
      applied. Anatomic changes resulting from the most commonly performed procedures
      (eg, glossectomy, pelvectomy, and mandibulectomy) will be presented with CT and
      MR images, multiplanar reconstructions, and schematic illustrations.
      Understanding of postsurgical CT and MR imaging findings is important to avoid
      misinterpretation and confusion. Familiarity with the typical postsurgical
      imaging appearance of the oral cavity and oropharynx is crucial for
      differentiating normal postsurgical changes from persistent or recurrent disease
      and for diagnosis of associated second primary malignancies. Knowledge of
      postsurgical findings is essential for analysis of the oral cavity and oropharynx
      and allows early diagnosis of tumor recurrence or typical complications after
      surgical reconstruction.

PMID- 25969937
TI  - Spondylolysis and Beyond: Value of SPECT/CT in Evaluation of Low Back Pain in
      Children and Young Adults.
AB  - Single photon emission computed tomography (SPECT)/computed tomography (CT) is
      ideally suited for assessment of low back pain in children and young adults.
      Spondylolysis is one of the most common structural causes of low back pain and is
      readily identified and characterized in terms of its chronicity and likelihood to
      heal. The value of SPECT/CT extends to identification and characterization of
      other causes of low back pain, including abnormalities of the posterior elements,
      developing vertebral endplate, transverse processes, and sacrum and sacroiliac
      joint. Some of the disease processes that are identifiable at SPECT/CT are
      similar to those that occur in adults (eg, facet hypertrophy) but may be
      accelerated in young patients by high-level athletic activities. Other processes
      (eg, limbus vertebrae) are more unique to children, related to injury of the
      developing spine. The authors review the spectrum of pars interarticularis
      abnormalities with emphasis on the imaging features of causes of pediatric low
      back pain other than spondylolysis.

PMID- 25969938
TI  - Pediatric vasculitis: recognizing multisystemic manifestations at body imaging.
AB  - Pediatric vasculitides are multisystem diseases that can be diagnostic challenges
      because of variable clinical manifestations. The clinical manifestation is
      determined by the size of the affected vessels, organs involved, extent of
      vascular injury, and underlying pathologic characteristics. Henoch-Schonlein
      purpura and Kawasaki disease are the two most common subtypes of pediatric
      vasculitis. Diagnosis of pediatric vasculitis can be difficult, and the outcome
      can be serious or fatal in the absence of timely intervention. Imaging plays a
      central role in establishing the diagnosis of vasculitis involving large- and
      medium-sized vessels, visualizing its vascular and extravascular manifestations,
      and monitoring the disease course and response to treatment. Although imaging
      cannot depict the vessel changes of small-vessel vasculitis directly, it can be
      used to detect tissue damage resulting from vessel inflammation. This article
      discusses the classification and clinical features of the major pediatric
      vasculitides. The imaging approach to and nonneurologic findings of major
      pediatric vasculitis subtypes are reviewed for the pediatric body imager.

PMID- 25969939
TI  - Catch a Wave: Doppler US Quiz: Resident and Fellow Education Feature.

PMID- 25969940
TI  - Pathways of lymphatic spread in gynecologic malignancies.
AB  - Precise radiologic evaluation of regional adenopathic involvement in pelvic
      gynecologic tumors is fundamental to clinical practice because of its prognostic
      and therapeutic significance. Likewise, the identification of metastatic
      adenopathies at posttreatment imaging is essential for assessing response and
      detecting recurrence. Similar to urologic neoplasms, gynecologic neoplasms most
      often spread regionally to the pelvic and retroperitoneal lymph nodes, following
      the normal drainage pathways of the pelvic organs. Familiarity with routes of
      dissemination, treatment options, and means of analyzing lymph node
      characteristics is crucial to determine the extent of disease. Two staging
      systems can be used in characterizing gynecologic malignancies: the FIGO
      (International Federation of Gynecology and Obstetrics) system, which is the most
      commonly and universally used, and the TNM (tumor, node, metastasis) system,
      which is based on clinical and/or pathologic classification. Anatomic assessment
      with multidetector computed tomography (CT) and magnetic resonance (MR) imaging
      is still the most commonly used technique for the detection of lymph node spread,
      which is mainly based on morphologic criteria, the most important of which is
      nodal size. However, size has limited diagnostic specificity. Consequently,
      functional imaging techniques such as diffusion-weighted MR imaging, positron
      emission tomography combined with CT, lymphoscintigraphy, and sentinel lymph node
      mapping, which are based on molecular and physiologic activity and allow more
      precise evaluation, are often incorporated into diagnostic imaging protocols for
      staging of gynecologic malignancies.

PMID- 25969941
TI  - Professional coaching in radiology: practice corner.

PMID- 25969942
TI  - Polypoid lesions of the gallbladder: disease spectrum with pathologic correlation
      erratum.

PMID- 25969943
TI  - Multidetector CT of Vascular Compression Syndromes in the Abdomen and Pelvis
      Erratum.

PMID- 25969945
TI  - Local dynamic range compensation for scanning electron microscope imaging system.
AB  - This is the extended project by introducing the modified dynamic range histogram
      modification (MDRHM) and is presented in this paper. This technique is used to
      enhance the scanning electron microscope (SEM) imaging system. By comparing with
      the conventional histogram modification compensators, this technique utilizes
      histogram profiling by extending the dynamic range of each tile of an image to
      the limit of 0-255 range while retains its histogram shape. The proposed
      technique yields better image compensation compared to conventional methods.

PMID- 25969946
TI  - Effect of Pregnancy on Adverse Outcomes After General Surgery.
AB  - IMPORTANCE: The literature regarding the occurrence of adverse outcomes following
      nonobstetric surgery in pregnant compared with nonpregnant women has conflicting
      findings. Those differing conclusions may be the result of inadequate adjustment
      for differences between pregnant and nonpregnant women. It remains unclear
      whether pregnancy is a risk factor for postoperative morbidity and mortality of
      the woman after general surgery. OBJECTIVE: To compare the risk of postoperative
      complications in pregnant vs nonpregnant women undergoing similar general
      surgical procedures. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective
      cohort study, data were obtained from the American College of Surgeons' National
      Surgical Quality Improvement Program participant user file from January 1, 2006,
      to December 31, 2011. Propensity-matched females based on 63 preoperative
      characteristics were matched 1:1 with nonpregnant women undergoing the same
      operations by general surgeons. Operations performed between January 1, 2006, and
      December 31, 2011, were analyzed for postoperative adverse events occurring
      within 30 days of surgery. MAIN OUTCOMES AND MEASURES: Rates of 30-day
      postoperative mortality, overall morbidity, and 21 individual postoperative
      complications were compared. RESULTS: The unmatched cohorts included 2764
      pregnant women (50.5% underwent emergency surgery) and 516,705 nonpregnant women
      (13.2% underwent emergency surgery) undergoing general surgery. After propensity
      matching, there were no meaningful differences in all 63 preoperative
      characteristics between 2539 pregnant and 2539 nonpregnant patients (all
      standardized differences, <0.1). The 30-day mortality rates were similar (0.4% in
      pregnant women vs 0.3% in nonpregnant women; P = .82), and the rate of overall
      morbidity was also not significantly different between pregnant vs nonpregnant
      patients (6.6% vs 7.4%; P = .30). CONCLUSIONS AND RELEVANCE: There was no
      significant difference in overall morbidity or 30-day mortality rates in pregnant
      and nonpregnant propensity-matched women undergoing similar general surgical
      operations. General surgery appears to be as safe for pregnant women as it is for
      nonpregnant women.

PMID- 25969944
TI  - Best clinical practice in botulinum toxin treatment for children with cerebral
      palsy.
AB  - Botulinum toxin A (BoNT-A) is considered a safe and effective therapy for
      children with cerebral palsy (CP), especially in the hands of experienced
      injectors and for the majority of children. Recently, some risks have been noted
      for children with Gross Motor Classification Scale (GMFCS) of IV and the risks
      are substantial for level V. Recommendations for treatment with BoNT-A have been
      published since 1993, with continuous optimisation and development of new
      treatment concepts. This leads to modifications in the clinical decision making
      process, indications, injection techniques, assessments, and evaluations. This
      article summarises the state of the art of BoNT-A treatment in children with CP,
      based mainly on the literature and expert opinions by an international paediatric
      orthopaedic user group. BoNT-A is an important part of multimodal management, to
      support motor development and improve function when the targeted management of
      spasticity in specific muscle groups is clinically indicated. Individualised
      assessment and treatment are essential, and should be part of an integrated
      approach chosen to support the achievement of motor milestones. To this end,
      goals should be set for both the long term and for each injection cycle. The
      correct choice of target muscles is also important; not all spastic muscles need
      to be injected. A more focused approach needs to be established to improve
      function and motor development, and to prevent adverse compensations and
      contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy
      to adulthood, and treatment should take into account the change in indications
      with age. 

PMID- 25969947
TI  - Modal kinematics for multisection continuum arms.
AB  - This paper presents a novel spatial kinematic model for multisection continuum
      arms based on mode shape functions (MSF). Modal methods have been used in many
      disciplines from finite element methods to structural analysis to approximate
      complex and nonlinear parametric variations with simple mathematical functions.
      Given certain constraints and required accuracy, this helps to simplify complex
      phenomena with numerically efficient implementations leading to fast
      computations. A successful application of the modal approximation techniques to
      develop a new modal kinematic model for general variable length multisection
      continuum arms is discussed. The proposed method solves the limitations
      associated with previous models and introduces a new approach for readily
      deriving exact, singularity-free and unique MSF's that simplifies the approach
      and avoids mode switching. The model is able to simulate spatial bending as well
      as straight arm motions (i.e., pure elongation/contraction), and introduces
      inverse position and orientation kinematics for multisection continuum arms. A
      kinematic decoupling feature, splitting position and orientation inverse
      kinematics is introduced. This type of decoupling has not been presented for
      these types of robotic arms before. The model also carefully accounts for
      physical constraints in the joint space to provide enhanced insight into
      practical mechanics and impose actuator mechanical limitations onto the
      kinematics thus generating fully realizable results. The proposed method is
      easily applicable to a broad spectrum of continuum arm designs. 

PMID- 25969948
TI  - Model for adhesion clutch explains biphasic relationship between actin flow and
      traction at the cell leading edge.
AB  - Cell motility relies on the continuous reorganization of a dynamic actin-myosin
      adhesion network at the leading edge of the cell, in order to generate protrusion
      at the leading edge and traction between the cell and its external environment.
      We analyze experimentally measured spatial distributions of actin flow, traction
      force, myosin density, and adhesion density in control and pharmacologically
      perturbed epithelial cells in order to develop a mechanical model of the actin
      adhesion-myosin self-organization at the leading edge. A model in which the F
      actin network is treated as a viscous gel, and adhesion clutch engagement is
      strengthened by myosin but weakened by actin flow, can explain the measured
      molecular distributions and correctly predict the spatial distributions of the
      actin flow and traction stress. We test the model by comparing its predictions
      with measurements of the actin flow and traction stress in cells with fast and
      slow actin polymerization rates. The model predicts how the location of the
      lamellipodium-lamellum boundary depends on the actin viscosity and adhesion
      strength. The model further predicts that the location of the lamellipodium
      lamellum boundary is not very sensitive to the level of myosin contraction. 

PMID- 25969950
TI  - Effects of storage medium and UV photofunctionalization on time-related changes
      of titanium surface characteristics and biocompatibility.
AB  - Storage in aqueous solution and ultraviolet (UV) photofunctionalization are two
      applicable methods to overcome the biological aging and increase the bioactivity
      of titanium. As information regarding the combined effects of storage medium and
      UV photofunctionalization has never been found in published literatures, this
      study focused on whether appropriate storage methods and UV
      photofunctionalization have synergistic effects on the biological properties of
      aged titanium surfaces. Titanium plates and discs were sandblasted and acid
      etched and then further prepared in five different modes as using different
      storage mediums (air or dH2 O) for 4 weeks and then with or without UV treatment.
      The surface characteristics were evaluated with scanning electron microscopy,
      contact angle measurements, and X-ray photoelectron spectroscopy. MC3T3-E1 cells
      were cultured on the surfaces, and cellular morphology, proliferation, alkaline
      phosphatase activity, and osteocalcin release were evaluated. The results showed
      that nanostructures were observed on water-stored titanium surfaces with a size
      of about 15 * 20 nm(2) . UV treatment was effective to remove the hydrocarbon
      contamination on titanium surfaces stored in either air or water. UV
      photofunctionalization further enhanced the already increased bioactivity of
      modSLA on initial cell attachment, proliferation, alkaline phosphatase activity,
      and osteocalcin release. Overall, UV photofunctionalization was effective in
      further enhancing the already increased bioactivity by using dH2 O as storage
      medium, and the effect of UV treatment was much more overwhelming than that of
      the storage medium. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 104B: 932-940, 2016.

PMID- 25969949
TI  - Molecular mechanisms of transcriptional control by Rev-erbalpha: An energetic
      foundation for reconciling structure and binding with biological function.
AB  - Rev-erbalpha and beta are nuclear receptors that function as transcriptional
      repressors of genes involved in regulating circadian rhythms, glucose, and
      cholesterol metabolism and the inflammatory response. Given these key functions,
      Rev-erbs are important drug targets for treatment of a number of human
      pathologies, including cancer, heart disease, and type II diabetes.
      Transcriptional repression by the Rev-erbs involves direct competition with
      transcriptional activators for target sites, but also recruitment by the Rev-erbs
      of the NCoR corepressor protein. Interestingly, Rev-erbs do not appear to
      interact functionally with a very similar corepressor, Smrt. Transcriptional
      repression by Rev-erbs is thought to occur in response to the binding of heme,
      although structural, and ligand binding studies in vitro show that heme and
      corepressor binding are antagonistic. We carried out systematic studies of the
      ligand and corepressor interactions to address the molecular basis for
      corepressor specificity and the energetic consequences of ligand binding using a
      variety of biophysical approaches. Highly quantitative fluorescence anisotropy
      assays in competition mode revealed that the Rev-erb specificity for the NCoR
      corepressor lies in the first two residues of the beta-strand in Interaction
      Domain 1 of NCoR. Our studies confirmed and quantitated the strong antagonism of
      heme and corepressor binding and significant stabilization of the corepressor
      complex by a synthetic ligand in vitro. We propose a model which reconciles the
      contradictory observations concerning the effects of heme binding in vitro and in
      live cells. 

PMID- 25969951
TI  - Nanospace-confinement copolymerization strategy for encapsulating polymeric
      sulfur into porous carbon for lithium-sulfur batteries.
AB  - Given their high theoretical energy density, lithium-sulfur (Li-S) batteries have
      recently attracted ever-increasing research interest. However, the dissolution of
      polysulfides and uncontrolled deposition of insoluble discharge product
      significantly hinder the cycling stability. Herein, a nanospace-confinement
      copolymerization strategy for encapsulating polymeric sulfur into porous carbon
      matrix is presented. The morphologies and sulfur contents of carbon/polymeric
      sulfur (C/PS) composites could be readily tailored by controlling the
      copolymerization time. Confining polymeric sulfur in the porous carbon with
      abundant interparticle pores facilitates rapid electronic/ionic transport and
      mitigates dissolution of polysulfides intermediates. More importantly, the
      organic sulfur units dispersed in the insoluble/insulating Li2S2/Li2S phase could
      prevent its irreversible deposition. Such nanostructure with tailored chemistry
      property permits the C/PS electrodes to exhibit enhanced cycling stability and
      high rate capability. The nanospace-confinement copolymerization strategy
      features general and facial advantages, which may provide new opportunities for
      the future development of advanced sulfur cathodes. 

PMID- 25969952
TI  - MDM2 binds and inhibits vitamin D receptor.
AB  - The E3 ubiquitin ligase and transcriptional repressor MDM2 is a potent inhibitor
      of the p53 family of transcription factors and tumor suppressors. Herein, we
      report that vitamin D receptor (VDR), another transcriptional regulator and
      probably, tumor suppressor, is also bound and inhibited by MDM2. This interaction
      was not affected by vitamin D ligand. VDR was ubiquitylated in the cell and its
      steady-state level was controlled by the proteasome. Strikingly, overproduced
      MDM2 reduced the level of VDR whereas knockdown of endogenous MDM2 increased the
      level of VDR. In addition to ubiquitin-marking proteins for degradation, MDM2,
      once recruited to promoters by DNA-binding interaction partners, can inhibit the
      transactivation of genes. Transient transfections with a VDR-responsive
      luciferase reporter revealed that low levels of MDM2 potently suppress VDR
      mediated transactivation. Conversely, knockdown of MDM2 resulted in a significant
      increase of transcript from the CYP24A1 and p21 genes, noted cellular targets of
      transactivation by liganded VDR. Our findings suggest that MDM2 negatively
      regulates VDR in some analogy to p53.

PMID- 25969953
TI  - Electrostatic nucleic acid nanoassembly enables hybridization chain reaction in
      living cells for ultrasensitive mRNA imaging.
AB  - Efficient approaches for intracellular delivery of nucleic acid reagents to
      achieve sensitive detection and regulation of gene and protein expressions are
      essential for chemistry and biology. We develop a novel electrostatic DNA
      nanoassembly that, for the first time, realizes hybridization chain reaction
      (HCR), a target-initiated alternating hybridization reaction between two hairpin
      probes, for signal amplification in living cells. The DNA nanoassembly has a
      designed structure with a core gold nanoparticle, a cationic peptide interlayer,
      and an electrostatically assembled outer layer of fluorophore-labeled hairpin DNA
      probes. It is shown to have high efficiency for cellular delivery of DNA probes
      via a unique endocytosis-independent mechanism that confers a significant
      advantage of overcoming endosomal entrapment. Moreover, electrostatic assembly of
      DNA probes enables target-initialized release of the probes from the nanoassembly
      via HCR. This intracellular HCR offers efficient signal amplification and enables
      ultrasensitive fluorescence activation imaging of mRNA expression with a
      picomolar detection limit. The results imply that the developed nanoassembly may
      provide an invaluable platform in low-abundance biomarker discovery and
      regulation for cell biology and theranostics. 

PMID- 25969954
TI  - Energy transfer and unusual decay behaviour of BaCa2Si3O9:Eu(2+),Mn(2+) phosphor.
AB  - In this work the photoluminescence (PL) of BaCa2Si3O9:Eu(2+),Mn(2+) and the
      energy transfer (ET) between Eu(2+) and Mn(2+) were examined. A series of powder
      samples with various Mn(2+) concentrations were prepared by high temperature
      solid state route. Phase purity was investigated using X-ray powder
      diffractometry. Emission and excitation spectra as well as diffuse reflectance
      spectra were recorded to elucidate the PL properties of co-doped
      BaCa2Si3O9:Eu(2+),Mn(2+). Furthermore, fluorescence lifetime measurements were
      performed. PL and lifetime measurements were carried out from 100 to 800 K and
      100 to 500 K, respectively. Moreover, external quantum efficiencies were
      determined and colour points were calculated. It turned out that ET from Eu(2+)
      to Mn(2+) is of a resonant type and occurs via dipole-quadrupole interactions.
      Temperature dependent PL measurements indicate high temperature stability of
      emission intensity in BaCa2Si3O9:Eu(2+),Mn(2+). Finally, it was found that
      fluorescence lifetimes of Eu(2+) BaCa2Si3O9 show an unusual increase with
      increasing temperature. 

PMID- 25969955
TI  - A robust method for assessing chemically induced mutagenic effects in the oral
      cavity of transgenic Big Blue(r) rats.
AB  - The Big Blue(r) (BB) in vivo mutation assay uses transgenic rodents to measure
      treatment-induced mutations in virtually any tissue. The BB assay can be
      conducted in rats or mice and is ideal for investigating tissue-specific
      mutagenic mode of action of tumor induction. Some tissues such as oral mucosa
      have not been thoroughly studied. Due to the small quantity and cartilaginous
      nature of oral cavity tissues, development of special prosection and DNA
      isolation methods was required to permit robust analysis of mutations in these
      tissues. Improved surgical methods permitted collection of adequate and
      reproducible quantities of tissue (~45 mg gingiva/buccal and ~30 mg
      gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen
      pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform
      extraction, to yield sufficient quantities of DNA from these tissues. In
      preliminary optimization work, mutant frequency (MF) in tongue and gingiva was
      increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct
      mutagen, N-ethyl-N-nitrosourea. The oral cavity carcinogen, 4-nitroquinoline-1
      oxide (4-NQO; 10 ppm in drinking water; 28 days), was qualified as a positive
      control for mutagenesis in oral tissues since it caused significant increases in
      cII MFs in gingiva/palate (50.2-fold) and gingiva/buccal tissues (21.3-fold), but
      not in liver or bone marrow (0.9- and 1.4-fold, respectively). These results are
      consistent with the observation that 4-NQO primarily induces tumors in oral
      cavity. Results also demonstrate the utility of the BB rat mutation assay and
      optimized methods for investigation of oral cavity mutagenicity, and by
      extension, analysis of other small and cartilaginous tissues.

PMID- 25969961
TI  - Joint symposium - 24th april 2014.

PMID- 25969962
TI  - A modeling approach to determine how much UV radiation is available across the UK
      and Ireland for health risk and benefit studies.
AB  - A detailed map of the available UV across the UK from 2003 to 2012 is provided. A
      suite of data derived from climatologies and satellite observations are used to
      calculate spectral UV irradiance and related weighted doses (erythema, DNA
      damage, vitamin D). The result is a well-validated tool that has two advantages:
      (i) the output is simulated spectral UV irradiance that can be weighted with any
      action spectrum for use in any research studies that require ambient UV data,
      (ii) reliance on instruments with planned operational lives of at least several
      years that ensures data and method homogeneity for extension to future studies.
      The model-derived doses are satisfactory validated against spectral ground-based
      measurements at two sites. According to the calculated climatology, the southern
      part of the UK receives 1.5-2 times more UV than the north during spring, summer
      and autumn. During wintertime, the UV doses in the far north are an order of
      magnitude lower than southern values. Even for the same latitude, regional
      variations of cloudiness result in doses at coastal sites being up to 25% higher
      than inland areas. 

PMID- 25969964
TI  - Expanding the Scope of our Journal to Include Molecular Diagnostics for
      Infectious Diseases.

PMID- 25969963
TI  - Prediction of small-for-gestational-age neonates: screening by maternal serum
      biochemical markers at 19-24 weeks.
AB  - OBJECTIVE: To investigate the value of maternal serum concentrations of placental
      growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), pregnancy
      associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin
      (beta-hCG) and alpha-fetoprotein (AFP) at 19-24 weeks' gestation, in combination
      with maternal factors and fetal biometry, in the prediction of delivery of small
      for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE) and
      examine the potential value of such assessment in deciding whether the third
      trimester scan should be performed at 32 and/or 36 weeks' gestation. METHODS:
      This was a screening study in 9715 singleton pregnancies, including 481 (5.0%)
      that delivered SGA neonates with birth weight < 5(th) percentile (SGA < 5(th) ),
      in the absence of PE. Multivariable logistic regression analysis was used to
      determine if screening by a combination of maternal factors, Z-scores of fetal
      head circumference, abdominal circumference and femur length, and log10 multiples
      of the median (MoM) values of PlGF, sFlt-1, PAPP-A, free beta-hCG or AFP had a
      significant contribution to the prediction of SGA neonates. A model was developed
      in selecting the gestational age for third-trimester assessment, at 32 and/or 36
      weeks, based on the results of screening at 19-24 weeks. RESULTS: Compared to the
      normal group, the mean log10 MoM value of PlGF was lower, AFP was higher and sFlt
      1, PAPP-A and free beta-hCG were not significantly different in the SGA < 5(th)
      group that delivered < 37 weeks. The detection rate (DR) of combined screening by
      maternal factors, fetal biometry and serum PlGF and AFP at 19-24 weeks was 100%,
      76% and 38% for SGA < 5(th) delivering < 32, 32-36 and >= 37 weeks' gestation,
      respectively, at a false-positive rate (FPR) of 10%. In a hypothetical model, it
      was estimated that, if the desired objective of prenatal screening is to predict
      about 80% of the cases of SGA < 5(th) , it would be necessary to select 11% of
      the population at the 19-24-week assessment to be reassessed at 32 weeks and 46%
      to be reassessed at 36 weeks; 54% would not require a third-trimester scan.
      CONCLUSION: Prenatal prediction of a high proportion of SGA neonates necessitates
      the undertaking of screening in the third trimester of pregnancy, in addition to
      assessment in the second trimester, and the timing of such screening, at 32
      and/or 36 weeks, should be contingent on the results of the assessment at 19-24
      weeks.

PMID- 25969965
TI  - Will the wall come tumbling down?

PMID- 25969966
TI  - Effects of 6 Weeks of Balance Training on Chronic Ankle Instability in Athletes:
      A Randomized Controlled Trial.
AB  - The objective of the present study was to determine the effectiveness of a 6-week
      balance training program on patients with Chronic Ankle Instability (CAI) in
      relation to the results obtained in Dynamic Balance, subjective feeling of
      instability and pain using a single-blind randomized controlled trial. 70
      athletes were randomly assigned to control or intervention group. The control
      group performed their usual training, and the intervention group was administered
      the same usual activity in addition to a balance program. The paired t-test was
      performed to evaluate the change scores in each group. The t-test for independent
      samples was performed to evaluate between-group differences in change scores.
      Significance level was assigned for p-values less than 0.05 for all analyses.
      There were significant differences between groups in change scores in CAIT and
      all of the SEBTs reach distances (p<0.001) but not in Pain (p=0.586). The effect
      sizes were larger for the outcomes measures that showed significant differences.
      In the within-group change, the experimental groups showed larger effect sizes in
      CAIT, SEBT posteromedial and SEBT posterolateral, and moderate effect sizes in
      SEBT anterior. Exercise therapy training based on multi-station balance tasks led
      to significant improvements in dynamic balance and self-reported sensation of
      instability in patients with CAI. 

PMID- 25969967
TI  - The Influence of Airway Tree Geometry and Ventilation Frequency on Airflow
      Distribution.
AB  - The human lung is known to be asymmetric and heterogeneous which leads to an
      inhomogeneous distribution of air. Within the scope of this paper the influence
      of the upper airway tree geometry on ventilation distribution and the differences
      between conventional mechanical ventilation (CMV) and high frequency oscillatory
      ventilation (HFOV) will be analyzed. The comparison is carried out under the
      assumption of positive pressure ventilation. Thereby, the mechanics of lung
      tissue is expected to play a minor role. Oscillatory flow is therefore generated
      numerically at a 3D model geometry of the upper human airways. For large enough
      frequencies in the range of HFOV (here 7 Hz) the shape of the velocity profiles
      changes, but this had no measurable influence on the flow distribution. The flow
      division is rather governed by airway tree geometry, i.e., branch length,
      curvature, and tortuosity. A convective net transport of fresh air to the distal
      branches occurs due to the relocation of mass during ins-/expiration driven by
      secondary flow. However, a mixing by secondary flow plays a minor role as was
      suggested by the visualization of particle pathlines. The phenomenon of steady
      streaming is further investigated by calculating the mean flow of one breathing
      cycle. Streaming was found to contribute only to a minor percentage to the
      overall mass transport in the upper lung airways.

PMID- 25969968
TI  - Challenges of Change: Can 7 years be better than 6 years for a plastic surgery
      trainee?

PMID- 25969969
TI  - The discrete scar in prominent ear correction: a digital 3-dimensional analysis
      to determine the ideal incision for otoplasty.
AB  - INTRODUCTION: Various postauricular incision sites can be used for prominent ear
      correction depending on technique and surgeon preference. No study has previously
      looked at the most aesthetic (least visible) location for the postauricular scar.
      We investigated the visibility of various scar locations on the posterior ear
      from a third person perspective through a "Visibility Arc"-a formal assessment of
      the range of degrees where a particular scar is visible. The objective was to
      determine the least visible incision-that is, the scar with the shortest
      visibility arc. METHODS: Normal ears were marked with 3 different color markers
      to simulate postoperative scar position, namely, (1) black in auriculocephalic
      sulcus, (2) blue in the sulcus of the antihelical fold/groove, and (3) green
      between black and blue. Starting laterally from the right ear toward the left
      ear, each head was photographed across 180 degrees posteriorly, at 10-degree
      intervals to determine which colored line (corresponding to a particular scar
      location) was visible over what "visibility arc." RESULTS: Forty individual ears
      were analyzed. Scars located in the sulcus of the antihelical fold had the
      shortest average visible arc, which was a 70-degree arc. The auriculocephalic
      sulcus had the largest visibility arc, and was most obvious of all of the scar
      locations-a 100-degree arc. The scar location in between these 2 locations had an
      80-degree arc. CONCLUSIONS: The least visible scar for pinnaplasty rests in the
      groove of the antihelix posteriorly, with scars slightly medial to this almost as
      discrete. The most visible scars when viewed from behind will be those in the
      "traditional" location of the auriculocephalic sulcus.

PMID- 25969970
TI  - Scaphoid fracture nonunion treated with pronator quadratus pedicled vascularized
      bone graft and headless compression screw.
AB  - The purpose of our retrospective study was to evaluate the outcomes of scaphoid
      fracture nonunion treated with a pronator quadratus pedicled vascularized bone
      graft and a headless compression screw with regard to early wrist and thumb
      mobilization. From January 2008 to June 2011, 27 patients (20 men and 7 women;
      mean age, 24 years; age range, 15-32 years) with scaphoid fracture nonunion were
      treated with a pronator quadratus pedicled vascularized bone graft and a headless
      compression screw, and who met our inclusion criteria, including symptomatic
      scaphoid waist fracture nonunion with or without compromised vascularity and
      carpal instability. We evaluated radiologic assessment (correction of carpal
      instability and union rate). And, overall clinical results were also graded using
      the wrist range of motion, the modified Mayo wrist score, and disabilities of the
      arm, shoulder and hand score. All patients achieved bony union in a mean of 11.5
      weeks (range, 8-18 weeks). The mean radiolunate and scapholunate angles improved
      from -12.3 degrees (range, -38.0 to 4.5 degrees) and 62.8 degrees (range, 50.0
      72.5 degrees) preoperatively to -1.4 degrees (range, -14.5 to 6.5 degrees) and
      48.5 degrees (range, 40.5-63.5 degrees) at the follow-up. The final average range
      of motion was as follows: wrist flexion, 73 degrees (range, 65-85 degrees);
      extension, 69 degrees (range, 60-80 degrees); ulnar deviation, 36 degrees (range,
      15-50 degrees); and radial deviation, 22 degrees (range, 10-35 degrees). The
      average postoperative modified Mayo wrist score and disabilities of the arm,
      shoulder and hand score were 92 points (range, 78-100 points) and 11 points
      (range, 0-32 points), respectively. Our results suggest that a pronator quadratus
      pedicled vascularized bone graft and internal fixation with a headless
      compression screw can yield satisfactory functional and radiographic outcomes in
      the treatment of scaphoid fracture nonunion.

PMID- 25969971
TI  - Free fibula reconstruction of distal tibial defects after sarcoma surgery.
AB  - Distal tibial tumor ablation results in combined soft tissue and bone defect that
      involves the ankle joint. This area is unique and problematic because it combines
      low caliber limb size, relatively soft tissue deficiency, suboptimal bone and
      soft tissue healing ability, and the need to sustain increased mechanical loads.
      The management is difficult, controversial, and traditionally was treated by
      primary amputation. We present our experience with a limb sparing surgery using
      biological reconstruction.Between 2004 and 2007, 5 patients with malignant bone
      tumors of the distal tibia underwent tumor resection and reconstruction with free
      vascularized osteoseptocutaneous fibula flap. The average age was 33.2 years
      (range, 11-62 years). In all cases, a skin island was harvested and used for
      wound closure. Arthrodesis of the ankle joint was preformed in all patients.
      Double fixation system was used to provide stability and avoid flap rotation.All
      flaps survived. There were no major complications. One patient had partial loss
      of the skin paddle that was treated conservatively. Callous formation was
      documented after an average time of 4 months, partial weight bearing after an
      average time of 4 months, and full weight bearing after an average time of 11.5
      months. All patients regained almost normal ambulation within a year.

PMID- 25969972
TI  - Nonpersistence of basal cell carcinoma after diagnostic shave biopsy:
      reconstruction when specimen is negative during surgery.
AB  - BACKGROUND: Initial tissue sampling for diagnosis of suspected basal cell
      carcinoma (BCC) is typically performed using a shave biopsy technique or punch
      biopsy. METHODS: Our realization of no residual BCC findings after excision in
      some patients with biopsy-proven BCC diagnosed through a shave biopsy prompted us
      to conduct a retrospective study of all consecutive patients with 127 BCCs who
      were treated in our department between 2006 and 2012. All patients with
      incompletely excised BCCs after shave biopsy diagnosis were operated on by a
      single surgeon (R.G.), eliminating variables in preoperative evaluation and
      surgical technique including margin control and reconstructive approach. Patient
      demographics, initial BCC site, size, subtype, duration between shave biopsy and
      surgery, size of excision, findings of intraoperative frozen section analysis,
      type of closure technique, and final pathology reports were analyzed. RESULTS:
      There were 108 residual BCCs diagnosed after surgical excision. Most of the108
      BCCs were nodular (52) or micronodular (21) subtype. Eighteen BCCs were treated
      with excision and primary closure. Flap procedure was performed in 64 BCCs after
      excision. Twenty-six defects after excision were reconstructed using skin grafts.
      There was no evidence of residual BCC in 15% of BCCs (19 patients) after surgical
      treatment. In other words, shave biopsy was found to be curative in 15% of BCCs.
      Seven patients in no residual BCC group received excision and primary closure.
      Eleven patients underwent flap reconstruction, whereas only 1 patient required
      skin grafting. Most of the patients in this group had nodular or micronodular
      type BCC (14/19). CONCLUSIONS: We were not able to identify any clinically
      significant predictors of residual versus no residual BCC, at least within the
      context of the current study. Although most patients diagnosed with BCC had
      residual tumors for which they received surgical treatment, 15% of patients had
      to undergo primary closure, skin graft, or flap procedure for negative residual
      BCC. We would like to promote greater awareness on the subject among plastic
      surgeons treating BCCs. And, it is extremely important that the informed consent
      should include statements regarding possible reconstructive procedures even in
      the case of nonpersistent tumor from medicolegal standpoint.

PMID- 25969973
TI  - Superficial peroneal neurocutaneous flap based on an anterior tibial artery
      perforator for forefoot reconstruction.
AB  - The distally based superficial peroneal neurocutaneous (SPNC) island flap has
      been widely used for foot reconstruction. It is based on the descending branch of
      the peroneal artery perforator. However, damage to the perimalleolar
      vascularization or anatomic variations of the descending branch often causes flap
      necrosis. Because septocutaneous perforators from the anterior tibial artery
      participate in the vascular network of superficial peroneal nerve in the distal
      lower leg, a modified SPNC flap is designed based on the anterior tibial artery
      perforator. Seven patients with soft tissue defect over the forefoot were treated
      by this modified technique. Six patients had accompanied injuries at the lateral
      perimalleolar region, and 1 patient had an anatomic variation of the descending
      branch of the peroneal artery perforator. The size of defect ranged from 12 * 5
      to 15 * 9 cm. All 7 flaps survived completely without complications. The size of
      the flaps ranged from 13 * 6 to 16 * 10 cm. No severe venous congestion occurred.
      The mean follow-up was 9.4 months (range, 6-14 months). All patients were
      satisfied with the texture and color of the flaps. Two patients complained about
      the thickness of the flaps, but did not want further operation. The donor sites
      healed uneventfully and no painful neuroma occurred. In conclusion, the modified
      SPNC flap based on an anterior tibial artery perforator is a feasible salvage
      procedure when the traditional design is unreliable. It can provide sufficient
      and superior coverage for large forefoot defect.

PMID- 25969974
TI  - The effect of community based-academic partnerships on student knowledge about
      plastic surgery and interest in medicine.
AB  - BACKGROUND: Programs specific to plastic surgery are necessary to dispel common
      myths and increase interest in the field. In a previous publication by the
      authors, a community outreach program was developed for these reasons for middle
      school students. In the current study, we expanded on the previous research and
      collected objective data to assess students' initial interest in medicine and
      knowledge about plastic surgery, compared to their interest and knowledge
      afterward. METHODS: The program previously developed by the authors was modified
      and performed for the students at various community outreach events and included
      a PowerPoint presentation, case didactics, and hands-on activities. A test about
      plastic surgery and questionnaire about interest in the medical field and
      becoming a doctor was given to each student before and after the program.
      RESULTS: One hundred seventy-nine students participated in the program from 2009
      to 2013. The pretest mean score was 6.50 of 12 questions whereas the posttest
      mean score was 9.72 (P = <0.001). After participation in the program, 27% of
      students that answered "no" or "unsure" about interest in the medical field on
      the pretest changed their answer to "yes," on the posttest, and 17% of students
      that answered "no" or "unsure" about interest in becoming a doctor on the pretest
      changed their answer to "yes," on the posttest (P = <0.001). CONCLUSIONS: A
      plastic surgery community outreach program is beneficial in increasing students'
      interest in the field of medicine as a whole, and more specifically in the field
      of plastic surgery.

PMID- 25969975
TI  - Residency characteristics that matter most to plastic surgery applicants: a multi
      institutional analysis and review of the literature.
AB  - PURPOSE: The National Residency Matching Program Match is a very unique process
      in which applicants and programs are coupled to each other based on a ranking
      system. Although several studies have assessed features plastic surgery programs
      look for in applicants, no study in the present plastic surgery literature
      identifies which residency characteristics are most important to plastic surgery
      applicants. Therefore, we sought to perform a multi-institutional assessment as
      to which factors plastic surgery residency applicants consider most important
      when applying for residency. METHODS: A validated and anonymous questionnaire
      containing 37 items regarding various program characteristics was e-mailed to 226
      applicants to New York University, Albany, University of Michigan, and University
      of Southern California plastic surgery residency programs. Applicants were asked
      to rate each feature on a scale from 1 to 10, with 10 being the most important.
      The 37 variables were ranked by the sum of the responses. The median rating and
      interquartile range as well as the mean for each factor was then calculated. A
      Wilcoxon signed rank test was used to compare medians in rank order. RESULTS: A
      total of 137 completed questionnaires were returned, yielding a 61% response
      rate. The characteristics candidates considered most important were impressions
      during the interview, experiences during away rotations, importance placed on
      resident training/support/mentoring by faculty, personal experiences with
      residents, and the amount of time spent in general surgery. The characteristics
      candidates considered least important were second-look experiences,
      compensation/benefits, program reputation from Internet forums, accessibility of
      program coordinator, opportunity for laboratory research, and fellowship
      positions available at the program. CONCLUSIONS: Applicants value personal
      contact and time spent in general surgery when selecting residency programs. As
      the number of integrated programs continues to grow, programs will benefit from
      learning what factors their applicants value most.

PMID- 25969976
TI  - The extended distally based sural neurocutaneous flap for foot and ankle
      reconstruction: a retrospective review of 10 years of experience.

PMID- 25969977
TI  - Lymph node flap based on the right transverse cervical artery as a donor site for
      lymph node transfer.

PMID- 25969978
TI  - Paramuscular perforators in dieap flap for breast reconstruction: an important
      variation in perforator flap nomenclature: reply.

PMID- 25969979
TI  - Electronic Cigarette and Traditional Cigarette Use among Middle and High School
      Students in Florida, 2011-2014.
AB  - Recent youth trends in the prevalence of e-cigarette and traditional cigarette
      use in Florida were examined in a cross-sectional, representative state sample
      from 2011 to 2014. Traditional cigarette use among youth declined during the
      study period. Experimentation with and past 30-day use of e-cigarettes among
      Florida youth tripled over 4 years. Past 30-day e-cigarette use exceeded
      traditional cigarette use in 2014; 10.8% of high school and 4.0% of middle school
      students reported recent e-cigarette use, compared with 8.7% of high school and
      2.9% of middle school students for traditional cigarettes (P<0.001). By 2014,
      20.5% of high school and 8.5% of middle school students reported ever use of e
      cigarettes. Among ever e-cigarette users in 2014, 30.3% of high school and 42.2%
      of middle school students had never smoked traditional cigarettes. Given the
      concern that significant rates of e-cigarette use by U.S. adolescents may have a
      negative effect on public health, further review of e-cigarette advertising,
      marketing, sales, and use among U.S. youth is warranted. 

PMID- 25969980
TI  - Multi-Contrast Imaging and Digital Refocusing on a Mobile Microscope with a Domed
      LED Array.
AB  - We demonstrate the design and application of an add-on device for improving the
      diagnostic and research capabilities of CellScope--a low-cost, smartphone-based
      point-of-care microscope. We replace the single LED illumination of the original
      CellScope with a programmable domed LED array. By leveraging recent advances in
      computational illumination, this new device enables simultaneous multi-contrast
      imaging with brightfield, darkfield, and phase imaging modes. Further, we scan
      through illumination angles to capture lightfield datasets, which can be used to
      recover 3D intensity and phase images without any hardware changes. This digital
      refocusing procedure can be used for either 3D imaging or software-only focus
      correction, reducing the need for precise mechanical focusing during field
      experiments. All acquisition and processing is performed on the mobile phone and
      controlled through a smartphone application, making the computational microscope
      compact and portable. Using multiple samples and different objective
      magnifications, we demonstrate that the performance of our device is comparable
      to that of a commercial microscope. This unique device platform extends the field
      imaging capabilities of CellScope, opening up new clinical and research
      possibilities.

PMID- 25969981
TI  - Alginate hydrogels coated with chitosan for wound dressing.
AB  - In this work, a coating of chitosan onto alginate hydrogels was realized using
      the water-soluble hydrochloride form of chitosan (CH-Cl), with the dual purpose
      of imparting antibacterial activity and delaying the release of hydrophilic
      molecules from the alginate matrix. Alginate hydrogels with different calcium
      contents were prepared by the internal setting method and coated by immersion in
      a CH-Cl solution. Structural analysis by cryo-scanning electron microscopy was
      carried out to highlight morphological alterations due to the coating layer.
      Tests in vitro with human mesenchymal stromal cells (MSC) were assessed to check
      the absence of toxicity of CH-Cl. Swelling, stability in physiological solution
      and release characteristics using rhodamine B as the hydrophilic model drug were
      compared to those of relative uncoated hydrogels. Finally, antibacterial activity
      against Escherichia coli was tested. Results show that alginate hydrogels coated
      with chitosan hydrochloride described here can be proposed as a novel medicated
      dressing by associating intrinsic antimicrobial activity with improved sustained
      release characteristics. 

PMID- 25969982
TI  - Evaluation of Glaucomatous Damage via Functional Magnetic Resonance Imaging, and
      Correlations Thereof with Anatomical and Psychophysical Ocular Findings.
AB  - PURPOSE: To evaluate the functional magnetic resonance imaging (fMRI) response to
      binocular visual stimulation and the association thereof with structural ocular
      findings and psychophysical test results in patients with glaucoma, and controls.
      METHODS: Cross-sectional study. Participants underwent a complete ophthalmic
      examination, including Humphrey 24-2 visual field (VF) testing and optical
      coherence tomography. Binocular VF in each quadrant was determined using an
      integrated method. Patients with glaucoma were assigned to three subgroups:
      initial, asymmetrical and severe glaucoma. Regions of interest (ROIs) were
      determined anatomically. fMRI (3 T) was performed using a bilaterally presented
      polar angle stimulus, and the accompanying changes in blood oxygen level
      dependent (BOLD) signals were obtained from the occipital poles and calcarine
      ROIs. We used generalized estimation equation models to compare anatomical and
      functional data between the groups. RESULTS: A total of 25 subjects were
      enrolled, of whom 17 had glaucoma and 8 were controls. Significant associations
      between quadrant binocular VF sensitivities and fMRI responses were found in the
      occipital pole ROIs (p = 0.033) and the calcarine ROIs (p = 0.045). In glaucoma
      severity subgroup analysis, retinal nerve fiber layer (RNFL) thickness was
      associated with the BOLD response of the calcarine and occipital pole ROIs (p =
      0.002 and 0.026, respectively). The initial and asymmetrical glaucoma subgroups
      had similar binocular VF sensitivities and RNFL thicknesses, but distinct BOLD
      responses. CONCLUSIONS: The response of the visual cortex to binocular
      stimulation was associated with binocular VF sensitivity. RNFL thickness was
      associated with the BOLD response of the calcarine and occipital pole ROIs.

PMID- 25969983
TI  - Impact of facial conformation on canine health: corneal ulceration.
AB  - Concern has arisen in recent years that selection for extreme facial morphology
      in the domestic dog may be leading to an increased frequency of eye disorders.
      Corneal ulcers are a common and painful eye problem in domestic dogs that can
      lead to scarring and/or perforation of the cornea, potentially causing blindness.
      Exaggerated juvenile-like craniofacial conformations and wide eyes have been
      suspected as risk factors for corneal ulceration. This study aimed to quantify
      the relationship between corneal ulceration risk and conformational factors
      including relative eyelid aperture width, brachycephalic (short-muzzled) skull
      shape, the presence of a nasal fold (wrinkle), and exposed eye-white. A 14 month
      cross-sectional study of dogs entering a large UK based small animal referral
      hospital for both corneal ulcers and unrelated disorders was carried out. Dogs
      were classed as affected if they were diagnosed with a corneal ulcer using
      fluorescein dye while at the hospital (whether referred for this disorder or
      not), or if a previous diagnosis of corneal ulcer(s) was documented in the dogs'
      histories. Of 700 dogs recruited, measured and clinically examined, 31 were
      affected by corneal ulcers. Most cases were male (71%), small breed dogs (mean+/-
      SE weight: 11.4+/-1.1 kg), with the most commonly diagnosed breed being the Pug.
      Dogs with nasal folds were nearly five times more likely to be affected by
      corneal ulcers than those without, and brachycephalic dogs (craniofacial ratio
      <0.5) were twenty times more likely to be affected than non-brachycephalic dogs.
      A 10% increase in relative eyelid aperture width more than tripled the ulcer
      risk. Exposed eye-white was associated with a nearly three times increased risk.
      The results demonstrate that artificially selecting for these facial
      characteristics greatly heightens the risk of corneal ulcers, and such selection
      should thus be discouraged to improve canine welfare. 

PMID- 25969984
TI  - Specific Inhibitory Effect of kappa-Carrageenan Polysaccharide on Swine Pandemic
      2009 H1N1 Influenza Virus.
AB  - The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug
      resources and the vaccine industry. Carrageenan, an extractive of red algae, has
      been proven to inhibit infection and multiplication of various enveloped viruses.
      The aim of this study was to examine the ability of kappa-carrageenan to inhibit
      swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral
      ability of kappa-carrageenan. It was here demonstrated that kappa-carrageenan had
      no cytotoxicity at concentrations below 1000 MUg/ml. Hemagglutination, 50% tissue
      culture infectious dose (TCID50) and cytopathic effect (CPE) inhibition assays
      showed that kappa-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731)
      and A/California/04/2009 H1N1 (CA04) replication in a dose-dependent fashion.
      Mechanism studies show that the inhibition of SW731 multiplication and mRNA
      expression was maximized when kappa-carrageenan was added before or during
      adsorption. The result of Hemagglutination inhibition assay indicate that kappa
      carrageenan specifically targeted HA of SW731 and CA04, both of which are
      pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8),
      A/WSN/1933 H1N1 (WSN), A/Swine/Beijing/26/2008 H1N1 (SW26),
      A/Chicken/Shandong/LY/2008 H9N2 (LY08), and A/Chicken/Shandong/ZB/2007 H9N2
      (ZB07) viruses. Immunofluorescence assay and Western blot showed that kappa
      carrageenan also inhibited SW731 protein expression after its internalization
      into cells. These results suggest that kappa-carrageenan can significantly
      inhibit SW731 replication by interfering with a few replication steps in the
      SW731 life cycles, including adsorption, transcription, and viral protein
      expression, especially interactions between HA and cells. In this way, kappa
      carrageenan might be a suitable alternative approach to therapy meant to address
      anti-IAV, which contains an HA homologous to that of SW731. 

PMID- 25969985
TI  - Biomass Increases Go under Cover: Woody Vegetation Dynamics in South African
      Rangelands.
AB  - Woody biomass dynamics are an expression of ecosystem function, yet biomass
      estimates do not provide information on the spatial distribution of woody
      vegetation within the vertical vegetation subcanopy. We demonstrate the ability
      of airborne light detection and ranging (LiDAR) to measure aboveground biomass
      and subcanopy structure, as an explanatory tool to unravel vegetation dynamics in
      structurally heterogeneous landscapes. We sampled three communal rangelands in
      Bushbuckridge, South Africa, utilised by rural communities for fuelwood
      harvesting. Woody biomass estimates ranged between 9 Mg ha(-1) on gabbro geology
      sites to 27 Mg ha(-1) on granitic geology sites. Despite predictions of woodland
      depletion due to unsustainable fuelwood extraction in previous studies, biomass
      in all the communal rangelands increased between 2008 and 2012. Annual biomass
      productivity estimates (10-14% p.a.) were higher than previous estimates of 4%
      and likely a significant contributor to the previous underestimations of modelled
      biomass supply. We show that biomass increases are attributable to growth of
      vegetation <5 m in height, and that, in the high wood extraction rangeland, 79%
      of the changes in the vertical vegetation subcanopy are gains in the 1-3 m height
      class. The higher the wood extraction pressure on the rangelands, the greater the
      biomass increases in the low height classes within the subcanopy, likely a strong
      resprouting response to intensive harvesting. Yet, fuelwood shortages are still
      occurring, as evidenced by the losses in the tall tree height class in the high
      extraction rangeland. Loss of large trees and gain in subcanopy shrubs could
      result in a structurally simple landscape with reduced functional capacity. This
      research demonstrates that intensive harvesting can, paradoxically, increase
      biomass and this has implications for the sustainability of ecosystem service
      provision. The structural implications of biomass increases in communal
      rangelands could be misinterpreted as woodland recovery in the absence of three
      dimensional, subcanopy information.

PMID- 25969986
TI  - Contribution of Disulfide Bridges to the Thermostability of a Type A Feruloyl
      Esterase from Aspergillus usamii.
AB  - The contribution of disulfide bridges to the thermostability of a type A feruloyl
      esterase (AuFaeA) from Aspergillus usamii E001 was studied by introducing an
      extra disulfide bridge or eliminating a native one from the enzyme. MODIP and
      DbD, two computational tools that can predict the possible disulfide bridges in
      proteins for thermostability improvement, and molecular dynamics (MD) simulations
      were used to design the extra disulfide bridge. One residue pair A126-N152 was
      chosen, and the respective amino acid residues were mutated to cysteine. The wild
      type AuFaeA and its variants were expressed in Pichia pastoris GS115. The
      temperature optimum of the recombinant (re-) AuFaeAA126C-N152C was increased by 6
      degrees C compared to that of re-AuFaeA. The thermal inactivation half-lives of
      re-AuFaeAA126C-N152C at 55 and 60 degrees C were 188 and 40 min, which were 12.5-
      and 10-folds longer than those of re-AuFaeA. The catalytic efficiency (kcat/Km)
      of re-AuFaeAA126C-N152C was similar to that of re-AuFaeA. Additionally, after
      elimination of each native disulfide bridge in AuFaeA, a great decrease in
      expression level and at least 10 degrees C decrease in thermal stability of
      recombinant AuEaeA variants were also observed. 

PMID- 25969987
TI  - Alcelaphine Herpesvirus-1 (Malignant Catarrhal Fever Virus) in Wildebeest
      Placenta: Genetic Variation of ORF50 and A9.5 Alleles.
AB  - Alcelaphine herpesvirus-1 (AlHV-1), a causative agent of malignant catarrhal
      fever in cattle, was detected in wildebeest (Connochaetes taurinus) placenta
      tissue for the first time. Although viral load was low, the finding of viral DNA
      in over 50% of 94 samples tested lends support to the possibility that placental
      tissue could play a role in disease transmission and that wildebeest calves are
      infected in utero. Two viral loci were sequenced to examine variation among virus
      samples obtained from wildebeest and cattle: the ORF50 gene, encoding the lytic
      cycle transactivator protein, and the A9.5 gene, encoding a novel polymorphic
      viral glycoprotein. ORF50 was well conserved with six newly discovered alleles
      differing at only one or two base positions. In contrast, while only three new
      A9.5 alleles were discovered, these differed by up to 13% at the nucleotide level
      and up to 20% at the amino acid level. Structural homology searching performed
      with the additional A9.5 sequences determined in this study adds power to recent
      analysis identifying the four-helix bundle cytokine interleukin-4 (IL4) as the
      major homologue. The majority of MCF virus samples obtained from Tanzanian cattle
      and wildebeest encoded A9.5 polypeptides identical to the previously
      characterized A9.5 allele present in the laboratory maintained AlHV-1 C500
      strain. This supports the view that AlHV-1 C500 is suitable for the development
      of a vaccine for wildebeest-associated MCF. 

PMID- 25969988
TI  - Bacterial and fungal communities in a degraded ombrotrophic peatland undergoing
      natural and managed re-vegetation.
AB  - The UK hosts 15-19% of global upland ombrotrophic (rain fed) peatlands that are
      estimated to store 3.2 billion tonnes of carbon and represent a critical upland
      habitat with regard to biodiversity and ecosystem services provision. Net
      production is dependent on an imbalance between growth of peat-forming Sphagnum
      mosses and microbial decomposition by microorganisms that are limited by cold,
      acidic, and anaerobic conditions. In the Southern Pennines, land-use change,
      drainage, and over 200 years of anthropogenic N and heavy metal deposition have
      contributed to severe peatland degradation manifested as a loss of vegetation
      leaving bare peat susceptible to erosion and deep gullying. A restoration
      programme designed to regain peat hydrology, stability and functionality has
      involved re-vegetation through nurse grass, dwarf shrub and Sphagnum re
      introduction. Our aim was to characterise bacterial and fungal communities, via
      high-throughput rRNA gene sequencing, in the surface acrotelm/mesotelm of
      degraded bare peat, long-term stable vegetated peat, and natural and managed
      restorations. Compared to long-term vegetated areas the bare peat microbiome had
      significantly higher levels of oligotrophic marker phyla (Acidobacteria,
      Verrucomicrobia, TM6) and lower Bacteroidetes and Actinobacteria, together with
      much higher ligninolytic Basidiomycota. Fewer distinct microbial sequences and
      significantly fewer cultivable microbes were detected in bare peat compared to
      other areas. Microbial community structure was linked to restoration activity and
      correlated with soil edaphic variables (e.g. moisture and heavy metals). Although
      rapid community changes were evident following restoration activity, restored
      bare peat did not approach a similar microbial community structure to non-eroded
      areas even after 25 years, which may be related to the stabilisation of historic
      deposited heavy metals pollution in long-term stable areas. These primary
      findings are discussed in relation to bare peat oligotrophy, re-vegetation
      recalcitrance, rhizosphere-microbe-soil interactions, C, N and P cycling,
      trajectory of restoration, and ecosystem service implications for peatland
      restoration. 

PMID- 25969989
TI  - Biological Control of the Chagas Disease Vector Triatoma infestans with the
      Entomopathogenic Fungus Beauveria bassiana Combined with an Aggregation Cue:
      Field, Laboratory and Mathematical Modeling Assessment.
AB  - BACKGROUND: Current Chagas disease vector control strategies, based on chemical
      insecticide spraying, are growingly threatened by the emergence of pyrethroid
      resistant Triatoma infestans populations in the Gran Chaco region of South
      America. METHODOLOGY AND FINDINGS: We have already shown that the
      entomopathogenic fungus Beauveria bassiana has the ability to breach the insect
      cuticle and is effective both against pyrethroid-susceptible and pyrethroid
      resistant T. infestans, in laboratory as well as field assays. It is also known
      that T. infestans cuticle lipids play a major role as contact aggregation
      pheromones. We estimated the effectiveness of pheromone-based infection boxes
      containing B. bassiana spores to kill indoor bugs, and its effect on the vector
      population dynamics. Laboratory assays were performed to estimate the effect of
      fungal infection on female reproductive parameters. The effect of insect exuviae
      as an aggregation signal in the performance of the infection boxes was estimated
      both in the laboratory and in the field. We developed a stage-specific matrix
      model of T. infestans to describe the fungal infection effects on insect
      population dynamics, and to analyze the performance of the biopesticide device in
      vector biological control. CONCLUSIONS: The pheromone-containing infective box is
      a promising new tool against indoor populations of this Chagas disease vector,
      with the number of boxes per house being the main driver of the reduction of the
      total domestic bug population. This ecologically safe approach is the first
      proven alternative to chemical insecticides in the control of T. infestans. The
      advantageous reduction in vector population by delayed-action fungal
      biopesticides in a contained environment is here shown supported by mathematical
      modeling.

PMID- 25969990
TI  - Loss of Murine FOXO3 in Cells of the Myeloid Lineage Enhances Myelopoiesis but
      Protects from K/BxN-Serum Transfer-Induced Arthritis.
AB  - FOXO transcription factors have a highly conserved role in regulating
      transcription of genes involved in differentiation, cell cycle arrest, apoptosis
      and DNA repair. Loss of FOXO3 in mice has previously been shown to result in a
      myeloproliferative disease. In agreement with this, we found that an independent
      Foxo3 null mouse strain, Foxo3Kca, exhibits an increase in neutrophils in the
      spleen, bone marrow and blood. This coincides with an expansion of myeloid
      progenitor cells including pre-granulocyte-macrophage progenitors (Pre-GMs) and
      granulocyte-macrophage progenitors (GMPs). Surprisingly, despite neutrophilia,
      the severity of passive serum transfer arthritis was markedly attenuated in
      Foxo3Kca mice. These defects appear to be at least partially intrinsic to the
      myeloid lineage, as deleting Foxo3 specifically from myeloid cells using LysMCre
      also leads to an elevated number of neutrophils and protection from K/BxN-serum
      transfer-induced arthritis. 

PMID- 25969991
TI  - The effect of active learning methodologies on the teaching of pharmaceutical
      care in a Brazilian pharmacy faculty.
AB  - BACKGROUND: In recent years, pharmacists have been involved in expanded patient
      care responsibilities, for example patient counseling in self-medication,
      medication review and pharmaceutical care, which require graduates to develop the
      necessary competences. Consequently, reorientation of pharmacy education has
      become necessary. As such, active learning strategies have been introduced into
      classrooms to increase problem-solving and critical thinking skills of students.
      The objective of this study was to evaluate the performance and perceptions of
      competency of students in a new pharmaceutical care course that uses active
      learning methodologies. METHODS: This pharmaceutical care course was conducted in
      the first semester of 2014, in the Federal University of Sergipe. In the
      pharmaceutical care course, active learning methods were used, consisting of
      dialogic classroom expository, simulation and case studies. Student learning was
      evaluated using classroom tests and instruments that evaluated the perception of
      competency in pharmaceutical care practice. Furthermore, students' satisfaction
      with the course was evaluated. RESULTS: Thirty-three students completed the four
      evaluations used in the course (i.e., a discursive written exam, seminars, OSCE,
      and virtual patient); 25 were female (75.75%), and the median age was 23.43 (SD
      2.82) years. The overall mean of student scores, in all evaluation methods was
      7.97 (SD 0.59) on a scale of 0 to 10 points, and student performance on the
      virtual patient method was statistically superior to other methods. With respect
      to the perception of competency in pharmaceutical care practice, a comparison of
      pre- and post-test scores revealed statistically significant improvement for all
      evaluated competences. At the end of the semester, the students presented
      positive opinions of the pharmaceutical care course. CONCLUSIONS: The results
      suggest that an active learning course can enhance the learning of pharmaceutical
      care competences. In future studies it will be necessary to compare active
      learning to traditional methods.

PMID- 25969992
TI  - MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer.
AB  - miRNAs are predicted to control the activity of approximately 60% of all protein
      coding genes participating in the regulation of several cellular processes and
      diseases, including cancer. Recently, we have demonstrated that miR-187 is
      significantly downregulated in prostate cancer (PCa) and here we propose a
      proteomic approach to identify its potential targets. For this purpose, PC-3
      cells were transiently transfected with miR-187 precursor and miRNA mimic
      negative control. Proteins were analyzed by a two-dimensional difference gel
      electrophoresis (2D-DIGE) and defined as differentially regulated if the observed
      fold change was +/-1.06. Then, MALDI-TOF MS analysis was performed after protein
      digestion and low abundance proteins were identified by LC-MS/MS. Peptides were
      identified by searching against the Expasy SWISS PROT database, and target
      validation was performed both in vitro by western blot and qRT-PCR and in
      clinical samples by qRT-PCR, immunohistochemistry and ELISA. DIGE analysis showed
      9 differentially expressed spots (p<0.05) and 7 showed a down-regulated
      expression upon miR-187 re-introduction. Among these targets we identified
      aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3 expression was significantly
      downregulated in PC3, LNCaP and DU-145 cells after miR-187 re-introduction.
      Supporting these data, the expression of ALDH1A3 was found significantly
      (p<0.0001) up-regulated in PCa samples and inversely correlated (p<0.0001) with
      miR-187 expression, its expression being directly associated with Gleason score
      (p = 0.05). The expression of ALDH1A3 was measured in urine samples to evaluate
      the predictive capability of this biomarker for the presence of PCa and, at a
      signification level of 10%, PSA and also ALDH1A3 were significantly associated
      with a positive biopsy of PCa. In conclusion, our data illustrate for the first
      time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the
      utility of using this protein as a new biomarker for PCa. 

PMID- 25969993
TI  - Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to
      Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer
      Development and Treatment Using Gefitinib.
AB  - BACKGROUND: Basal-like and triple negative breast cancer (TNBC) share common
      molecular features, poor prognosis and a propensity for metastasis to the brain.
      Amplification of epidermal growth factor receptor (EGFR) occurs in ~50% of basal
      like breast cancer, and mutations in the epidermal growth factor receptor (EGFR)
      have been reported in up to ~ 10% of Asian TNBC patients. In non-small cell lung
      cancer several different mutations in the EGFR tyrosine kinase domain confer
      sensitivity to receptor tyrosine kinase inhibitors, but the tumourigenic
      potential of EGFR mutations in breast cells and their potential for targeted
      therapy is unknown. MATERIALS AND METHODS: Constructs containing wild type, G719S
      or E746-A750 deletion mutant forms of EGFR were transfected into the MCF10A
      breast cells and their tumorigenic derivative, MCF10CA1a. The effects of EGFR
      over-expression and mutation on proliferation, migration, invasion, response to
      gefitinib, and tumour formation in vivo was investigated. Copy number analysis
      and whole exome sequencing of the MCF10A and MCF10CA1a cell lines were also
      performed. RESULTS: Mutant EGFR increased MCF10A and MCF10CA1a proliferation and
      MCF10A gefitinib sensitivity. The EGFR-E746-A750 deletion increased MCF10CA1a
      cell migration and invasion, and greatly increased MCF10CA1a xenograft tumour
      formation and growth. Compared to MCF10A cells, MCF10CA1a cells exhibited large
      regions of gain on chromosomes 3 and 9, deletion on chromosome 7, and mutations
      in many genes implicated in cancer. CONCLUSIONS: Mutant EGFR enhances the
      oncogenic properties of MCF10A cell line, and increases sensitivity to gefitinib.
      Although the addition of EGFR E746-A750 renders the MCF10CA1a cells more
      tumourigenic in vivo it is not accompanied by increased gefitinib sensitivity,
      perhaps due to additional mutations, including the PIK3CA H1047R mutation, that
      the MCF10CA1a cell line has acquired. Screening TNBC/basal-like breast cancer for
      EGFR mutations may prove useful for directing therapy but, as in non-small cell
      lung cancer, accompanying mutations in PIK3CA may confer gefitinib resistance.

PMID- 25969995
TI  - Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza
      Viruses and Respiratory Droplet Transmission in Ferrets.
AB  - The seasonality of influenza virus infections in temperate climates and the role
      of environmental conditions like temperature and humidity in the transmission of
      influenza virus through the air are not well understood. Using ferrets housed at
      four different environmental conditions, we evaluated the respiratory droplet
      transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant
      virus, the etiologic virus of a swine to human summertime infection) and
      concurrently characterized the aerosol shedding profiles of infected animals.
      Comparisons were made among the different temperature and humidity conditions and
      between the two viruses to determine if the H3N2 variant virus exhibited enhanced
      capabilities that may have contributed to the infections occurring in the summer.
      We report here that although increased levels of H3N2 variant virus were found in
      ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2
      virus, enhanced respiratory droplet transmission was not observed under any of
      the environmental settings. However, overall environmental conditions were shown
      to modulate the frequency of influenza virus transmission through the air.
      Transmission occurred most frequently at 23 degrees C/30%RH, while the levels of
      infectious virus in aerosols exhaled by infected ferrets agree with these
      results. Improving our understanding of how environmental conditions affect
      influenza virus infectivity and transmission may reveal ways to better protect
      the public against influenza virus infections. 

PMID- 25969994
TI  - Clinical and laboratory studies of the fate of intranasal allergen.
AB  - BACKGROUND: The precise way in which allergen is handled by the nose is unknown.
      The objective of this study was to determine recovery of Der p 1 allergen
      following nasal administration and to determine whether Der p 1 can be detected
      in nasal biopsies after natural exposure and nasal challenge to allergen.
      METHODS: (1) 20 nonatopic non-rhinitics were challenged with Der p 1 and recovery
      was measured by ELISA in the nasal wash, nasal mucus and induced sputum up to 30
      minutes. Particulate charcoal (<40 MUm) served as control. (2) In 8 subjects (5
      atopics), 30 to 60 minutes after challenge histological localisation of Der p 1
      in the nasal mucosal epithelium, subepithelial mucous glands and lamina propria
      was performed. Co-localisation of Der p 1 with macrophages and IgE-positive cells
      was undertaken. RESULTS: (1) Less than 25% of total allergen was retrievable
      after aqueous or particulate challenge, most from the nasal mucus during 1-5 min
      after the challenge. The median of carbon particles recovered was 9%. (2)
      Prechallenge Der p 1 staining was associated with the epithelium and
      subepithelial mucous glands. After challenge there was a trend for greater Der p
      1 deposition in atopics, but both atopics and nonatopics showed increases in the
      number of Der p 1 stained cells and stained tissue compartments. In atopics,
      increased eosinophils, macrophages and IgE positive cells co-localized with Der p
      1 staining. CONCLUSIONS: Der p 1 allergen is detected in nasal tissue independent
      of atopic status after natural exposure. After challenge the nose effectively
      retains allergen, which remains mucosally associated; in atopics there is greater
      Der p 1 deposition and inflammatory response than in nonatopics. These results
      support the hypothesis that nasal mucus and tissue act as a reservoir for the
      inhaled Der p 1 allergen leading to a persistent allergic inflammatory response
      in susceptible individuals.

PMID- 25969997
TI  - Method to Biomonitor the Cooked Meat Carcinogen 2-Amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine in Dyed Hair by Ultra-Performance Liquid
      Chromatography-Orbitrap High Resolution Multistage Mass Spectrometry.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic
      heterocyclic aromatic amine formed in cooked meat. The use of naturally colored
      hair containing PhIP can serve as a long-term biomarker of exposure to this
      carcinogen. However, the measurement of PhIP in dyed hair, a cosmetic treatment
      commonly used by the adult population, is challenging because the dye process
      introduces into the hair matrix a complex mixture of chemicals that interferes
      with the measurement of PhIP. The high-resolution scanning features of the
      Orbitrap Fusion mass spectrometer were employed to biomonitor PhIP in dyed hair.
      Because of the complexity of chemicals in the hair dye, the consecutive reaction
      monitoring of PhIP at the MS(3) scan stage was employed to selectively remove the
      isobaric interferences. The limit of quantification (LOQ) of PhIP was 84 parts
      per-trillion (ppt) employing 50 mg of hair. Calibration curves were generated in
      dyed hair matrixes and showed good linearity (40-1000 pg PhIP/g hair) with a
      goodness-of-fit regression value of r(2) > 0.9978. The within-day (between-day)
      coefficients of variation were 7.7% (17%) and 5.4% (6.1%), respectively, with
      dyed hair samples spiked with PhIP at 200 and 600 ppt. The levels of PhIP accrued
      in dyed hair from volunteers on a semicontrolled feeding study who ingested known
      levels of PhIP were comparable to the levels of PhIP accrued in hair of subjects
      with natural hair color. The method was successfully employed to measure PhIP in
      nondyed and dyed hair biospecimens of participants in a case-control study of
      colorectal adenoma on their regular diet. 

PMID- 25969996
TI  - Study of the role of cytosolic phospholipase A2 alpha in eicosanoid generation
      and thymocyte maturation in the thymus.
AB  - The thymus is a primary lymphoid organ, home of maturation and selection of
      thymocytes for generation of functional T-cells. Multiple factors are involved
      throughout the different stages of the maturation process to tightly regulate T
      cell production. The metabolism of arachidonic acid by cyclooxygenases,
      lipoxygenases and specific isomerases generates eicosanoids, lipid mediators
      capable of triggering cellular responses. In this study, we determined the
      profile of expression of the eicosanoids present in the mouse thymus at different
      stages of thymocyte development. As the group IVA cytosolic phospholipase A2
      (cPLA2alpha) catalyzes the hydrolysis of phospholipids, thereby generating
      arachidonic acid, we further verified its contribution by including cPLA2alpha
      deficient mice to our investigations. We found that a vast array of eicosanoids
      is expressed in the thymus, which expression is substantially modulated through
      thymocyte development. The cPLA2alpha was dispensable in the generation of most
      eicosanoids in the thymus and consistently, the ablation of the cPLA2alpha gene
      in mouse thymus and the culture of thymuses from human newborns in presence of
      the cPLA2alpha inhibitor pyrrophenone did not impact thymocyte maturation. This
      study provides information on the eicosanoid repertoire present during thymocyte
      development and suggests that thymocyte maturation can occur independently of
      cPLA2alpha. 

PMID- 25969999
TI  - Adoptive transfer of transforming growth factor-?1-induced CD4+CD25+ regulatory T
      cells prevents immune response-mediated spontaneous abortion.
AB  - The effects of adoptive transfer of transforming growth factor (TGF)-beta1
      induced regulatory T (Treg) cells in preventing spontaneous abortion in mice were
      investigated. CD4+CD25- cells were isolated from the spleens of pregnant CBA/J
      mice and induced into Treg cells positive for CD4, CD25 and forkhead box P3
      (FOXP3) ex vivo using interleukin (IL)-2 and TGF-beta1. CBA/J mice were mated
      with DBA/2J mice to establish a model of spontaneous abortion and, on the first
      day of pregnancy, mice were injected intravenously with 2 * 105 either freshly
      isolated Treg cells or those induced with TGF-beta1. After 14 days, the surviving
      and reabsorbed fetuses in both groups were counted, and serum cytokine
      concentrations were measured by ELISA. Adoptive transfer of CD4+CD25+ or TGF
      beta1-induced Treg cells significantly reduced the fetal resorption rate,
      increased serum IL-10 and TGF-beta1 concentrations and decreased interferon-gamma
      levels. In conclusion, the results of the present study indicate that adoptive
      transfer of TGF-beta1-induced Treg cells prevents spontaneous abortion in mice by
      increasing the secretion of T helper (Th) 2 cytokines and decreasing the
      secretion of Th1 cytokines.

PMID- 25969998
TI  - Hydroquinone-assisted synthesis of branched au-ag nanoparticles with polydopamine
      coating as highly efficient photothermal agents.
AB  - Despite the success of galvanic replacement in preparing hollow nanostructures
      with diversified morphologies via the replacement reaction between sacrificial
      metal nanoparticles (NPs) seeds and less active metal ions, limited advances are
      made for producing branched alloy nanostructures. In this paper, we report an
      extended galvanic replacement for preparing branched Au-Ag NPs with Au-rich core
      and Ag branches using hydroquinone (HQ) as the reductant. In the presence of HQ,
      the preformed Ag seeds are replaceable by Au and, in turn, supply the growth of
      Ag branches. By altering the feed ratio of Ag seeds, HAuCl4, and HQ, the size and
      morphology of the NPs are tunable. Accordingly, the surface plasmon resonance
      absorption is tuned to near-infrared (NIR) region, making the branched NPs as
      potential materials in photothermal therapy. The branched NPs are further coated
      with polydopamine (PDA) shell via dopamine polymerization at room temperature. In
      comparison with bare NPs, PDA-coated branched Au-Ag (Au-Ag@PDA) NPs exhibit
      improved stability, biocompatibility, and photothermal performance. In vitro
      experiments indicate that the branched Au-Ag@PDA NPs are competitive agents for
      photothermal ablation of cancer cells. 

PMID- 25970000
TI  - Double Sequential Defibrillation for Refractory Ventricular Fibrillation: A Case
      Report.
AB  - A 40-year-old male struck his chest against a pole during a basketball game and
      had sudden out-of-hospital cardiac arrest. After bystander cardiopulmonary
      resuscitation, fire and emergency medical services personnel provided six
      defibrillation attempts prior to emergency department arrival. A 7th attempt in
      the emergency department using a different vector was unsuccessful. On the 8th
      attempt, using a second defibrillator with defibrillator pads placed adjacent to
      the primary set of defibrillator pads, two shocks were administered in near
      simultaneous fashion. The double sequential defibrillation was successful and the
      patient had return of spontaneous circulation at the next pulse check. He
      recovered in the intensive care unit, was discharged home 1 month later, and
      continues to follow up in clinic over 1 year later with a Cerebral Performance
      Category score of 1 (short-term memory deficits).

PMID- 25970001
TI  - Primary Immunodeficiencies with Elevated IgE.
AB  - In recent years a number of primary immunodeficiencies (PIDs) characterized by
      elevated Immunoglobulin E (IgE) levels have been uncovered and termed as Hyper
      IgE syndrome (HIES). In addition to the elevated levels of IgE, patients with
      these PIDs display a spectrum of infections by staphylococci and fungi, and in
      some cases viruses, particularly affecting skin and lungs. Most of these PIDs
      also have a non-infectious phenotype, comprising musculoskeletal, vascular, and
      neurological abnormalities. The genetic basis for the majority of conditions with
      elevated IgE has now been established and includes mutations in STAT3, DOCK8,
      TYK2, and most recently PGM3 molecules. However, in some patients with the
      relevant phenotype, mutations in these molecules are not identified, suggesting
      additional genetic etiologies of HIES not yet discovered. As the immunological
      and molecular basis of HIES is being unraveled, important insights are emerging
      that may have implications for our understanding of basic principles of
      immunology and protective immunity as well as for the pathogenesis and clinical
      management of patients with these complex and challenging PIDs. In this review,
      are presented the current knowledge on the clinical presentation, infectious
      phenotype, and the genetic and immunological pathogenesis of hyper-IgE syndromes
      as well as some other PIDs with elevated levels of IgE. 

PMID- 25970002
TI  - Integration of Ligand Field Molecular Mechanics in Tinker.
AB  - The ligand field molecular mechanics (LFMM) method for transition-metal complexes
      has been integrated in Tinker, an easily available and popular molecular modeling
      software package. The capability to calculate LFMM potentials has been provided
      by extending the functional forms of the Tinker package as well as by integrating
      routines for calculating the ligand field stabilization energy (LFSE), which is
      central to LFMM. The capabilities of the implementation are illustrated by both
      static calculations on the two spin states of [Fe(NH3)6](2+) and on
      [Cu(NH3)m](2+) (m = 4, 5, 6) and dynamic (LFMD) simulations of an FeN6-type spin
      crossover compound. In addition to showing that results obtained with the Tinker
      LFMM implementation are consistent with those of experiment and other
      computational methods and programs, we note that whereas LFMM is able to handle
      the conventional tetragonal Jahn-Teller distortion of the bond distances in
      [Cu(NH3)6](2+), the LFSE term is also necessary in order to obtain even
      qualitatively correct coordination geometries for the two lower-coordinate copper
      complexes. 

PMID- 25970003
TI  - Self-Assembly of Protein Nanofibrils Orchestrates Calcite Step Movement through
      Selective Nonchiral Interactions.
AB  - The recognition of atomically distinct surface features by adsorbed biomolecules
      is central to the formation of surface-templated peptide or protein
      nanostructures. On mineral surfaces such as calcite, biomolecular recognition of,
      and self-assembly on, distinct atomic kinks and steps could additionally
      orchestrate changes to the overall shape and symmetry of a bulk crystal. In this
      work, we show through in situ atomic force microscopy (AFM) experiments that an
      acidic 20 kDa cement protein from the barnacle Megabalanus rosa (MRCP20) binds
      specifically to step edge atoms on {1014} calcite surfaces, remains bound and
      further assembles over time to form one-dimensional nanofibrils. Protein
      nanofibrils are continuous and organized at the nanoscale, exhibiting striations
      with a period of ca. 45 nm. These fibrils, templated by surface steps of a
      preferred geometry, in turn selectively dissolve underlying calcite features
      displaying the same atomic arrangement. To demonstrate this, we expose the
      protein solution to bare and fibril-associated rhombohedral etch pits to reveal
      that nanofibrils accelerate only the movement of fibril-forming steps when
      compared to undecorated steps exposed to the same solution conditions. Calcite
      mineralized in the presence of MRCP20 results in asymmetric crystals defined by
      frustrated faces with shared mirror symmetry, suggesting a similar step-selective
      behavior by MRCP20 in crystal growth. As shown here, selective surface
      interactions with step edge atoms lead to a cooperative regime of calcite
      modification, where templated long-range protein nanostructures shape crystals. 

PMID- 25970004
TI  - Tetrabenzoporphyrin and -mono-, -cis-di- and Tetrabenzotriazaporphyrin
      Derivatives: Electrochemical and Spectroscopic Implications of meso CH Group
      Replacement with Nitrogen.
AB  - Nonperipherally hexyl-substituted metal-free tetrabenzoporphyrin (2H-TBP, 1a)
      tetrabenzomonoazaporphyrin (2H-TBMAP, 2a), tetrabenzo-cis-diazaporphyrin (2H
      TBDAP, 3a), tetrabenzotriazaporphyrin (2H-TBTAP, 4a), and phthalocyanine (2H-Pc,
      5a), as well as their copper complexes (1b-5b), were synthesized. As the number
      of meso nitrogen atoms increases from zero to four, lambdamax of the Q-band
      absorption peak becomes red-shifted by almost 100 nm, and extinction coefficients
      increased at least threefold. Simultaneously the blue-shifted Soret (UV) band
      substantially decreased in intensity. These changes were related to the relative
      electron-density of each macrocycle expressed as the group electronegativity sum
      of all meso N and CH atom groups, ?chiR. X-ray photoelectron spectroscopy
      differentiated between the three different types of macrocyclic nitrogen atoms
      (the Ninner, (NH)inner, and Nmeso) in the metal-free complexes. Binding energies
      of the Nmeso and Ninner,Cu atoms in copper chelates could not be resolved. Copper
      insertion lowered especially the cathodic redox potentials, while all four
      observed redox processes occurred at larger potentials as the number of meso
      nitrogens increased. Computational chemical methods using density functional
      theory confirmed 1b to exhibit a Cu(II) reduction prior to ring-based reductions,
      while for 2b, Cu(II) reduction is the first reductive step only if the
      nonperipheral substituents are hydrogen. When they are methyl groups, it is the
      second reduction process; when they are ethyl, propyl, or hexyl, it becomes the
      third reductive process. Spectro-electrochemical measurements showed redox
      processes were associated with a substantial change in intensity of at least two
      main absorbances (the Q and Soret bands) in the UV spectra of these compounds. 

PMID- 25970005
TI  - Time Dependence of Silica Surfaces on Their Interactions in Water and Alkaline
      Solutions.
AB  - Spherical silica particles are widely used to study the stability of colloids.
      This is because the stability of silica particles is important in industrial
      processes and also because monodispersed particles are available in various
      sizes, allowing fundamental investigations on colloidal stability to be
      performed. However, it is often assumed that the surface properties of silica do
      not change during the measurements, e.g. for 60 min. In the present study, we
      used the atomic force microscope to determine the validity of this assumption by
      studying the change in the surface microstructure of silica with its immersion
      time in water and alkaline solutions. The microstructure of silica surfaces was
      found to change with the immersion time, even in water. This change was
      especially large for solutions of high pH. These changes are explained in terms
      of the hydrogen bonds between the silanol groups protruding from the silica
      surfaces, whose length depends on the solution pH and the immersion time. 

PMID- 25970006
TI  - Detailed atomistic investigation of Fe-doped rutile phases.
AB  - We have investigated iron-doped rutile TiO2 in great detail by density functional
      theory (DFT) calculations. The influence of the Fe dopants on the structural and
      electronic properties are calculated. Three different dopant models are
      considered in this study, where iron is present in Fe(II), Fe(III), and Fe(IV)
      oxidation states. Our results indicate that the configuration of Fe(III), where
      two neighboring Ti sites are replaced by Fe dopants and an O vacancy locates in
      between, is the lowest-energy structure. The resulting Mobetabauer signatures are
      in excellent agreement with the available experimental literature data, thus
      supporting the proposed structural model. Although the crystal structure of doped
      rutile is not significantly altered, even for larger concentrations of dopant
      atoms, the local structure around Fe atoms can be strongly distorted, especially
      due to the presence of oxygen vacancies. Fe doping lowers the band gap and
      introduces midgap states. 

PMID- 25970008
TI  - Nudging smokers.

PMID- 25970007
TI  - Enhancement of antibody-dependent cell-mediated cytotoxicity by endowing IgG with
      FcalphaRI (CD89) binding.
AB  - Fc effector functions such as antibody-dependent cell-mediated cytotoxicity
      (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) are crucial to
      the efficacy of many antibody therapeutics. In addition to IgG, antibodies of the
      IgA isotype can also promote cell killing through engagement of myeloid lineage
      cells via interactions between the IgA-Fc and FcalphaRI (CD89). Herein, we
      describe a unique, tandem IgG1/IgA2 antibody format in the context of a
      trastuzumab variable domain that exhibits enhanced ADCC and ADCP capabilities.
      The IgG1/IgA2 tandem Fc format retains IgG1 FcgammaR binding as well as FcRn
      mediated serum persistence, yet is augmented with myeloid cell-mediated effector
      functions via FcalphaRI/IgA Fc interactions. In this work, we demonstrate anti
      human epidermal growth factor receptor-2 antibodies with the unique tandem
      IgG1/IgA2 Fc can better recruit and engage cytotoxic polymorphonuclear (PMN)
      cells than either the parental IgG1 or IgA2. Pharmacokinetics of IgG1/IgA2 in
      BALB/c mice are similar to the parental IgG, and far surpass the poor serum
      persistence of IgA2. The IgG1/IgA2 format is expressed at similar levels and with
      similar thermal stability to IgG1, and can be purified via standard protein A
      chromatography. The tandem IgG1/IgA2 format could potentially augment IgG-based
      immunotherapeutics with enhanced PMN-mediated cytotoxicity while avoiding many of
      the problems associated with developing IgAs. 

PMID- 25970009
TI  - Randomized trial of four financial-incentive programs for smoking cessation.
AB  - BACKGROUND: Financial incentives promote many health behaviors, but effective
      ways to deliver health incentives remain uncertain. METHODS: We randomly assigned
      CVS Caremark employees and their relatives and friends to one of four incentive
      programs or to usual care for smoking cessation. Two of the incentive programs
      targeted individuals, and two targeted groups of six participants. One of the
      individual-oriented programs and one of the group-oriented programs entailed
      rewards of approximately $800 for smoking cessation; the others entailed
      refundable deposits of $150 plus $650 in reward payments for successful
      participants. Usual care included informational resources and free smoking
      cessation aids. RESULTS: Overall, 2538 participants were enrolled. Of those
      assigned to reward-based programs, 90.0% accepted the assignment, as compared
      with 13.7% of those assigned to deposit-based programs (P<0.001). In intention-to
      treat analyses, rates of sustained abstinence from smoking through 6 months were
      higher with each of the four incentive programs (range, 9.4 to 16.0%) than with
      usual care (6.0%) (P<0.05 for all comparisons); the superiority of reward-based
      programs was sustained through 12 months. Group-oriented and individual-oriented
      programs were associated with similar 6-month abstinence rates (13.7% and 12.1%,
      respectively; P=0.29). Reward-based programs were associated with higher
      abstinence rates than deposit-based programs (15.7% vs. 10.2%, P<0.001). However,
      in instrumental-variable analyses that accounted for differential acceptance, the
      rate of abstinence at 6 months was 13.2 percentage points (95% confidence
      interval, 3.1 to 22.8) higher in the deposit-based programs than in the reward
      based programs among the estimated 13.7% of the participants who would accept
      participation in either type of program. CONCLUSIONS: Reward-based programs were
      much more commonly accepted than deposit-based programs, leading to higher rates
      of sustained abstinence from smoking. Group-oriented incentive programs were no
      more effective than individual-oriented programs. (Funded by the National
      Institutes of Health and CVS Caremark; ClinicalTrials.gov number, NCT01526265.).

PMID- 25970011
TI  - Is There Any Preferential Interaction of Ions of Ionic Liquids with DMSO and H2O?
      A Comparative Study from MD Simulation.
AB  - Recently, some binary ionic liquid (IL)/cosolvent systems have shown better
      performance than the pure ILs in fields such as CO2 absorption, catalysis,
      cellulose dissolution, and electrochemistry. However, interactions of ILs with
      cosolvents are still not well understood at the molecular level. In this work,
      H2O and DMSO were chosen as the representative protic and aprotic solvents to
      study the effect of cosolvent nature on solvation of a series of ILs by molecular
      dynamics simulations and quantum chemistry calculations. The concept of
      preferential interaction of ions was proposed to describe the interaction of
      cosolvent with cation and anion of the ILs. By comparing the interaction energies
      between IL and different cosolvents, it was found that there were significantly
      preferential interactions of anions of the ILs with water, but the same was not
      true for the interactions of cations/anions of the ILs with DMSO. Then, a
      detailed analysis and comparison of the interactions in IL/cosolvent systems,
      hydrogen bonds between cations and anions of the ILs, and the structure of the
      first coordination shells of the cations and the anions were performed to reveal
      the existing state of ions at different molar ratios of the cosolvent to a given
      IL. Furthermore, a systematic knowledge for the solvation of ions of the ILs in
      DMSO was given to understand cellulose dissolution in IL/cosolvent systems. The
      conclusions drawn from this study may provide new insight into the ionic
      solvation of ILs in cosolvents, and motivate further studies in the related
      applications. 

PMID- 25970012
TI  - Analysis of effectiveness of three forest interventionist techniques and proposal
      of a new and integrated model of forest restoration.
AB  - We assessed the efficacy of three different forest intervention techniques, in
      terms of phytosociological and edaphic responses, that were implemented in 2007.
      In a farm where trees are planted and managed for cellulose production as well as
      set aside for environmental conservation, four stands were analysed: three of
      them were considered degraded and were managed using different intervention
      techniques (transposition, perch, and abandonment), and a fourth stand comprising
      pristine vegetation was considered a control (reference). Floristic and
      phytosociology data were collected in three 10 * 10 m plots established in each
      stand. Also, a total of 48 soil samples were collected to analyse physical and
      chemical attributes of the topsoil for the different stands. In terms of
      biodiversity, all the treatments showed significantly lower values when compared
      to the reference area. However, the soils in all the treatment and reference
      stands are similar in terms of physical and chemical attributes. Taking into
      account the specificities of each restoration technique, we verified that the
      integrated use of a set of management practices, constituted by the (1)
      abandonment of the area and (2) following a selective killing of the eucalyptus,
      is the most suitable and promising model to provide fast and effective
      restoration in terms of environmental indicators.

PMID- 25970010
TI  - X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men.
AB  - BACKGROUND: The genetic basis of nonobstructive azoospermia is unknown in the
      majority of infertile men. METHODS: We performed array comparative genomic
      hybridization testing in blood samples obtained from 15 patients with
      azoospermia, and we performed mutation screening by means of direct Sanger
      sequencing of the testis-expressed 11 gene (TEX11) open reading frame in blood
      and semen samples obtained from 289 patients with azoospermia and 384 controls.
      RESULTS: We identified a 99-kb hemizygous loss on chromosome Xq13.2 that involved
      three TEX11 exons. This loss, which was identical in 2 patients with azoospermia,
      predicts a deletion of 79 amino acids within the meiosis-specific sporulation
      domain SPO22. Our subsequent mutation screening showed five novel TEX11
      mutations: three splicing mutations and two missense mutations. These mutations,
      which occurred in 7 of 289 men with azoospermia (2.4%), were absent in 384
      controls with normal sperm concentrations (P=0.003). Notably, five of those TEX11
      mutations were detected in 33 patients (15%) with azoospermia who received a
      diagnosis of azoospermia with meiotic arrest. Meiotic arrest in these patients
      resembled the phenotype of Tex11-deficient male mice. Immunohistochemical
      analysis showed specific cytoplasmic TEX11 expression in late spermatocytes, as
      well as in round and elongated spermatids, in normal human testes. In contrast,
      testes of patients who had azoospermia with TEX11 mutations had meiotic arrest
      and lacked TEX11 expression. CONCLUSIONS: In our study, hemizygous TEX11
      mutations were a common cause of meiotic arrest and azoospermia in infertile men.
      (Funded by the National Institutes of Health and others.).

PMID- 25970013
TI  - Ponatinib (Iclusig) for CML and Ph+ ALL.

PMID- 25970014
TI  - Bioinspired locomotion and grasping in water: the soft eight-arm OCTOPUS robot.
AB  - The octopus is an interesting model for the development of soft robotics, due to
      its high deformability, dexterity and rich behavioural repertoire. To investigate
      the principles of octopus dexterity, we designed an eight-arm soft robot and
      evaluated its performance with focused experiments. The OCTOPUS robot presented
      here is a completely soft robot, which integrates eight arms extending in radial
      direction and a central body which contains the main processing units. The front
      arms are mainly used for elongation and grasping, while the others are mainly
      used for locomotion. The robotic octopus works in water and its buoyancy is close
      to neutral. The experimental results show that the octopus-inspired robot can
      walk in water using the same strategy as the animal model, with good performance
      over different surfaces, including walking through physical constraints. It can
      grasp objects of different sizes and shapes, thanks to its soft arm materials and
      conical shape. 

PMID- 25970015
TI  - Risk of thrombosis in patients with myeloproliferative neoplasms and elevated
      platelet counts.

PMID- 25970016
TI  - Is the kinetoplast DNA a percolating network of linked rings at its critical
      point?
AB  - In this work we present a computational study of the kinetoplast genome, modelled
      as a large number of semiflexible unknotted loops, which are allowed to link with
      each other. As the DNA density increases, the systems shows a percolation
      transition between a gas of unlinked rings and a network of linked loops which
      spans the whole system. Close to the percolation transition, we find that the
      mean valency of the network, i.e. the average number of loops which are linked to
      any one loop, is around three, as found experimentally for the kinetoplast DNA
      (kDNA). Even more importantly, by simulating the digestion of the network by a
      restriction enzyme, we show that the distribution of oligomers, i.e. structures
      formed by a few loops which remain linked after digestion, quantitatively matches
      experimental data obtained from gel electrophoresis, provided that the density
      is, once again, close to the percolation transition. With respect to previous
      work, our analysis builds on a reduced number of assumptions, yet can still fully
      explain the experimental data. Our findings suggest that the kDNA can be viewed
      as a network of linked loops positioned very close to the percolation transition,
      and we discuss the possible biological implications of this remarkable fact. 

PMID- 25970018
TI  - Unmyelinated tactile cutaneous nerves signal erotic sensations.
AB  - INTRODUCTION: Intrapersonal touch is a powerful tool for communicating emotions
      and can among many things evoke feelings of eroticism and sexual arousal. The
      peripheral neural mechanisms of erotic touch signaling have been less studied. C
      tactile afferents (unmyelinated low-threshold mechanoreceptors), known to
      underpin pleasant aspects of touch processing, have been posited to play an
      important role. METHOD: In two studies, we investigated the relationship between
      C tactile activation and the perception of erotic and pleasant touch, using
      tactile brushing stimulation. In total, 66 healthy subjects (37 women, age range
      19-51 years) were examined. In study 1 (n = 20), five different stroking
      velocities were applied to the forearm and the inner thigh. The participants
      answered questions about partnership, mood, and touch. In study 2 (n = 46), the
      same five stroking velocities were applied to the forearm. The participants
      answered questions about partnership, touch, and sexuality. RESULTS: Both touch
      eroticism and pleasantness were rated significantly higher for C tactile optimal
      velocities compared with suboptimal velocities. No difference was found between
      the ratings of the thigh and the forearm. The velocity-dependent rating curves of
      pleasantness, intensity, and eroticism differed from each other. Pleasantness was
      best explained by a quadratic fit, intensity by a linear fit, and eroticism by
      both. A linear transformation of pleasantness and intensity predicted the
      observed eroticism ratings reliably. Eroticism ratings were negatively correlated
      with length of relationship. CONCLUSION: Touch was rated most erotic when
      perceived as pleasant and weak. In human hairy skin, perception of pleasantness
      is correlated with the firing rate of C tactile afferents, and perception of
      intensity is correlated with the firing rate of Abeta afferents. Accordingly,
      eroticism may be perceived most readily for touch stimuli that induce high
      activity in C tactile fibers and low activity in Abeta fibers.

PMID- 25970017
TI  - Multivalent Antigens for Promoting B and T Cell Activation.
AB  - Efficacious vaccines require antigens that elicit productive immune system
      activation. Antigens that afford robust antibody production activate both B and T
      cells. Elucidating the antigen properties that enhance B-T cell communication is
      difficult with traditional antigens. We therefore used ring-opening metathesis
      polymerization to access chemically defined, multivalent antigens containing both
      B and T cell epitopes to explore how antigen structure impacts B cell and T cell
      activation and communication. The bifunctional antigens were designed so that the
      backbone substitution level of each antigenic epitope could be quantified using
      (19)F NMR. The T cell peptide epitope was appended so that it could be liberated
      in B cells via the action of the endosomal protease cathepsin D, and this design
      feature was critical for T cell activation. Antigens with high BCR epitope
      valency induce greater BCR-mediated internalization and T cell activation than
      did low valency antigens, and these high-valency polymeric antigens were superior
      to protein antigens. We anticipate that these findings can guide the design of
      more effective vaccines. 

PMID- 25970019
TI  - Reaction Mechanisms in Carbohydrate-Active Enzymes: Glycoside Hydrolases and
      Glycosyltransferases. Insights from ab Initio Quantum Mechanics/Molecular
      Mechanics Dynamic Simulations.
AB  - Carbohydrate-active enzymes such as glycoside hydrolases (GHs) and
      glycosyltransferases (GTs) are of growing importance as drug targets. The
      development of efficient competitive inhibitors and chaperones to treat diseases
      related to these enzymes requires a detailed knowledge of their mechanisms of
      action. In recent years, sophisticated first-principles modeling approaches have
      significantly advanced in our understanding of the catalytic mechanisms of GHs
      and GTs, not only the molecular details of chemical reactions but also the
      significant implications that just the conformational dynamics of a sugar ring
      can have on these mechanisms. Here we provide an overview of the progress that
      has been made in the past decade, combining molecular dynamics simulations with
      density functional theory to solve these sweet mysteries of nature. 

PMID- 25970020
TI  - Consistency of self-reported drug use events in a mixed methods study of people
      who inject drugs.
AB  - BACKGROUND: Little is known about the consistency of information provided by
      people who inject drugs (PWID) during quantitative and qualitative interviews in
      mixed methods studies. OBJECTIVES: We illustrate the use of the intraclass
      correlation coefficient, descriptive statistics, and regression to assess the
      consistency of information provided during a mixed methods study of PWID living
      in Los Angeles and San Francisco, California, USA. METHODS: Age of first use of
      heroin, methamphetamine, marijuana, powder cocaine, and crack cocaine and first
      injection of heroin, methamphetamine, and powder cocaine were collected during an
      interviewer administered computer-assisted personal interview followed by an in
      depth qualitative interview (n = 102). RESULTS: Participants were 63% male,
      racially/ethnically diverse. 80.4% between the ages of 40 and 60 years old, 89%
      US-born, and 57% homeless. Consistency of self-reported data was adequate for
      most drug use events. Exact concordance between quantitative and qualitative
      measures of age of onset ranged from 18.2-50%. Event ordering was consistent
      across qualitative and quantitative results for 90.2% of participants. Analyses
      indicated that age of onset for heroin use, heroin injection, and injection of
      any drug was significantly lower when assessed by qualitative methods as compared
      to quantitative methods. CONCLUSION: While inconsistency will emerge during mixed
      method studies, confidence in the timing and ordering of major types of events
      such as drug initiation episodes appear to be warranted.

PMID- 25970021
TI  - Anion-induced Ag(I) self-assemblies with electron deficient aromatic ligands:
      anion-pi-system interactions as a driving force for templated coordination
      networks.
AB  - Three novel 1D, 2D and 3D coordination polymers were successfully isolated using
      nitrogen based 3,6-bis(2'-pyrimidyl)-1,2,4,5-tetrazine (BPymTz) and 2,4,6-tris(2
      pyrimidyl)-1,3,5-triazine (TPymT) ligands with Ag(I) ions. The formation of these
      supramolecular assemblies was templated through anion-pi-system interactions. 

PMID- 25970022
TI  - Molecular action of norgestimate: new developments.
AB  - BACKGROUND: Acne occurs because the sebaceous glands are overstimulated by high
      levels of androgens or are hypersensitive to normal levels of testosterone. In
      women with mild or moderate acne, the association of norgestimate (NG), and
      ethinyl estradiol (EE) is an effective treatment. This is related to the effect
      of oral contraceptives on androgen production and transport and the
      antiandrogenic properties of NG itself. DESIGN: The present work was undertaken
      to find out whether NG and its derivative, 17-deacetylnorgestimate(dNG), present
      steroid activities other than antiandrogen activities, using human progesterone
      receptor(PR), estrogen receptor alpha(ERalpha) and beta(ERbeta), glucocorticoid
      receptor(GR) and mineralocorticoid receptor(MR)-responsive cell lines. RESULTS:
      We confirmed that NG and its metabolite were progestogen partial agonists (EC50
      of 13 and 11.1 nM) and ERalpha selective agonists (EC50 of 30.4 and 43.4 nM), as
      well as full antagonists of low affinity for GR (IC50 of 325 and 255 nM) and
      moderate affinity for MR (IC50 of 81.2 and 83.7). CONCLUSION: We demonstrated
      that NG and dNG have full progestogen and weak estrogenic (through ERalpha)
      properties, which could explain in part the efficacy of NG in association with EE
      for the treatment of moderate acne in women. Moreover, their antagonist MR
      activity might have a favorable impact on cardiovascular risk, atherosclerosis
      and lipid profiles.

PMID- 25970023
TI  - Hydrophobic and moisture-stable metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) have proved to be very attractive for
      applications including gas storage, separation, sensing and catalysis. In
      particular, CO(2) separation from flue gas in post-combustion processes is one of
      the main focuses of research among the scientific community. One of the major
      issues that are preventing the successful commercialization of these novel
      materials is their high affinity towards water that not only compromises gas
      sorption capacity but also the chemical stability. In this paper, we demonstrate
      a novel post-synthesis modification approach to modify MOFs towards increasing
      hydrophobic behaviour and chemical stability against moisture without
      compromising CO(2) sorption capacity. Our approach consists of incorporating
      hydrophobic moieties on the external surface of the MOFs via physical adsorption.
      The rationale behind this concept is to increase the surface hydrophobicity in
      the porous materials without the need of introducing bulky functionalities inside
      the pore which compromises the sorption capacity toward other gases. We herein
      report preliminary results on routinely studied MOF materials [MIL-101(Cr) and
      NiDOBDC] demonstrating that the polymer-modified MOFs retain CO(2) sorption
      capacity while reducing the water adsorption up to three times, with respect to
      the un-modified materials, via an equilibrium effect. Furthermore, the water
      stability of the polymer-functionalized MOFs is significantly higher than the
      water stability of the bare material. Molecular dynamic simulations demonstrated
      that this equilibrium effect implies a fundamental and permanent change in the
      water sorption capacity of MOFs. This approach can also be employed to render
      moisture stability and selectivity to MOFs that find applications in gas
      separations, catalysis and sensing where water plays a critical role in
      compromising MOF performance and recyclability.

PMID- 25970026
TI  - Use of Arotinolol Pharmacotherapy to Treat Drug-induced Tremor: A Report of Three
      Cases.
AB  - OBJECTIVE: The aim of the present study is to demonstrate the effect of
      arotinolol on drug-induced tremor in psychiatric patients. METHODS: This is a
      case study of three psychiatric patients with the Diagnostic and Statistical
      Manual of Mental Disorders-IV (DSM-IV) diagnosis of major depressive disorder who
      were treated in inpatient or outpatient psychiatric settings with antidepressant
      or antipsychotics. Patients developed tremor. Arotinolol was started to treat the
      tremor. RESULTS: Drug-induced tremor almost resolved completely. No adverse
      effects were observed. CONCLUSION: We have presented a case series of drug
      induced tremors that responded well to treatment with arotinolol, which appears
      to be a safe and well-tolerated drug in the dose ranges used. The possible
      utility of arotinolol to treat drug-induced tremor deserves attention and further
      investigation.

PMID- 25970027
TI  - A Pragmatic Strategy for the Evaluation and Management of Anterior Canal Benign
      Positional Vertigo.

PMID- 25970028
TI  - Imaging Characteristics of Cerebellopontine Angle Chloroma.

PMID- 25970029
TI  - Spontaneous Otogenic Temporal Lobe Pneumatocele Presenting With Acute Aphasia.

PMID- 25970030
TI  - Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.
AB  - HYPOTHESIS: Gene expression changes occur in conjunction with hearing threshold
      changes after cochlear implantation. BACKGROUND: Between 30 and 50% of
      individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose
      residual hearing after cochlear implantation, reducing the benefits of EAS. The
      mechanism underlying this hearing loss is unknown; potential pathways include
      mechanical damage, inflammation, or tissue remodeling changes. METHODS: Guinea
      pigs were implanted in one ear with cochlear implant electrode arrays, with non
      implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14
      days. Hearing threshold changes were measured over time. Cochlear ribonucleic
      acid was analyzed using real-time quantitative reverse transcription-polymerase
      chain reaction from the following gene families: cytokines, tight junction
      claudins, ion and water (aquaporin) transport channels, gap junction connexins,
      and tissue remodeling genes. RESULTS: Significant increases in expression were
      observed for cochlear inflammatory genes (Cxcl1, IL-1beta, TNF-alpha, and
      Tnfrsf1a/b) and ion homeostasis genes (Scnn1gamma, Aqp3, and Gjb3). Upregulation
      of tissue remodeling genes (TGF-beta, MMP2, MMP9) as well as a paracrine gene
      (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with
      some recovery at 7 and 14 days after implantation. MM9 exhibited extreme
      upregulation of expression and was qualitatively associated with changes in
      hearing thresholds. CONCLUSION: Cochlear implantation induces similar changes as
      middle ear inflammation for genes involved in inflammation and ion and water
      transport function, whereas tissue remodeling changes differ markedly. The
      upregulation of MMP9 with hearing loss is consistent with previous findings
      linking stria vascularis vessel changes with cochlear implant-induced hearing
      loss.

PMID- 25970031
TI  - Estimating Occupational Illness, Injury, and Mortality in Food Production in the
      United States: A Farm-to-Table Analysis.
AB  - OBJECTIVES: The study provides a novel model and more comprehensive estimates of
      the burden of occupational morbidity and mortality in food-related industries,
      using a farm-to-table approach. METHODS: The authors analyzed 2008 to 2010 US
      Bureau of Labor Statistics data for private industries in the different stages of
      the farm-to-table model (production, processing, distribution and storage, and
      retail and preparation). RESULTS: The morbidity rate for food system industries
      was significantly higher than the morbidity rate for nonfood system industries
      (rate ratio = 1.62; 95% confidence interval = 1.30 to 2.01). Furthermore, the
      occupational mortality rate for food system industries was significantly higher
      than the national nonfood occupational mortality rate (rate ratio = 9.51; 95%
      confidence interval = 2.47 to 36.58). CONCLUSIONS: This is the first use of the
      farm-to-table model to assess occupational morbidity and mortality, and these
      findings highlighting specific workplace hazards across food system industries.

PMID- 25970032
TI  - Portable, Easy-to-Operate, and Antifouling Microcapsule Array Chips Fabricated by
      3D Ice Printing for Visual Target Detection.
AB  - Herein, we proposed a portable, easy-to-operate, and antifouling microcapsule
      array chip for target detection. This prepackaged chip was fabricated by
      innovative and cost-effective 3D ice printing integrating with
      photopolymerization sealing which could eliminate complicated preparation of wet
      chemistry and effectively resist outside contaminants. Only a small volume of
      sample (2 MUL for each microcapsule) was consumed to fulfill the assay. All the
      reagents required for the analysis were stored in ice form within the
      microcapsule before use, which guaranteed the long-term stability of microcapsule
      array chips. Nitrite and glucose were chosen as models for proof of concept to
      achieve an instant quantitative detection by naked eyes without the need of
      external sophisticated instruments. The simplicity, low cost, and small sample
      consumption endowed ice-printing microcapsule array chips with potential
      commercial value in the fields of on-site environmental monitoring, medical
      diagnostics, and rapid high-throughput point-of-care quantitative assay. 

PMID- 25970033
TI  - Synaptic activity regulates AMPA receptor trafficking through different recycling
      pathways.
AB  - Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type
      glutamate receptor (AMPAR) recycling, which is assumed to occur through a single
      local pathway. In this study, we present evidence that AMPAR recycling occurs
      through different pathways regulated by synaptic activity. Without synaptic
      stimulation, most AMPARs recycled in dynamin-independent endosomes containing the
      GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by
      transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the
      GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced
      AMPAR recycling had no effect on increased AMPAR levels with long-term
      potentiation (LTP) and little effect on decreased AMPAR levels with long-term
      depression. However, internalized AMPAR levels in TfR-containing recycling
      endosomes increased after LTP, indicating increased AMPAR recycling through the
      dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis
      is inconsistent with local recycling as a source of increased surface receptors,
      suggesting AMPARs are trafficked from other sites. 

PMID- 25970034
TI  - Cooperative base pair melting by helicase and polymerase positioned one
      nucleotide from each other.
AB  - Leading strand DNA synthesis requires functional coupling between replicative
      helicase and DNA polymerase (DNAP) enzymes, but the structural and mechanistic
      basis of coupling is poorly understood. This study defines the precise positions
      of T7 helicase and T7 DNAP at the replication fork junction with single-base
      resolution to create a structural model that explains the mutual stimulation of
      activities. Our 2-aminopurine studies show that helicase and polymerase both
      participate in DNA melting, but each enzyme melts the junction base pair
      partially. When combined, the junction base pair is melted cooperatively provided
      the helicase is located one nucleotide ahead of the primer-end. The synergistic
      shift in equilibrium of junction base pair melting by combined enzymes explains
      the cooperativity, wherein helicase stimulates the polymerase by promoting dNTP
      binding (decreasing dNTP Km), polymerase stimulates the helicase by increasing
      the unwinding rate-constant (kcat), consequently the combined enzymes unwind DNA
      with kinetic parameters resembling enzymes translocating on single-stranded DNA. 

PMID- 25970035
TI  - Social communication of predator-induced changes in Drosophila behavior and germ
      line physiology.
AB  - Behavioral adaptation to environmental threats and subsequent social transmission
      of adaptive behavior has evolutionary implications. In Drosophila, exposure to
      parasitoid wasps leads to a sharp decline in oviposition. We show that exposure
      to predator elicits both an acute and learned oviposition depression, mediated
      through the visual system. However, long-term persistence of oviposition
      depression after predator removal requires neuronal signaling functions, a
      functional mushroom body, and neurally driven apoptosis of oocytes through
      effector caspases. Strikingly, wasp-exposed flies (teachers) can transmit egg
      retention behavior and trigger ovarian apoptosis in naive, unexposed flies
      (students). Acquisition and behavioral execution of this socially learned
      behavior by naive flies requires all of the factors needed for primary learning.
      The ability to teach does not require ovarian apoptosis. This work provides new
      insight into genetic and physiological mechanisms that underlie an ecologically
      relevant form of learning and mechanisms for its social transmission. 

PMID- 25970036
TI  - Solid-State Fabrication of SnS2/C Nanospheres for High-Performance Sodium Ion
      Battery Anode.
AB  - Tin disulfide (SnS2) has emerged as a promising anode material for sodium ion
      batteries (NIBs) due to its unique layered structure, high theoretical capacity,
      and low cost. Conventional SnS2 nanomaterials are normally synthesized using
      hydrothermal method, which is time-consuming and difficult to scale up for mass
      production. In this study, we develop a simple solid-state reaction method, in
      which the carbon-coated SnS2 (SnS2/C) anode materials were synthesized by
      annealing metallic Sn, sulfur powder, and polyacrylonitrile in a sealed vacuum
      glass tube. The SnS2/C nanospheres with unique layered structure exhibit a high
      reversible capacity of 660 mAh g(-1) at a current density of 50 mA g(-1) and
      maintain at 570 mAh g(-1) for 100 cycles with a degradation rate of 0.14% per
      cycle, demonstrating one of the best cycling performances in all reported SnS2/C
      anodes for NIBs to date. The superior cycling stability of SnS2/C electrode is
      attributed to the stable nanosphere morphology and structural integrity during
      charge/discharge cycles as evidenced by ex situ characterization. 

PMID- 25970037
TI  - Dysbiosis and Immune Dysregulation in Outer Space.
AB  - In space, the lifestyle, relative sterility of spaceship and extreme
      environmental stresses, such as microgravity and cosmic radiation, can compromise
      the balance between human body and human microbiome. An astronaut's body during
      spaceflight encounters increased risk for microbial infections and conditions
      because of immune dysregulation and altered microbiome, i.e. dysbiosis. This risk
      is further heightened by increase in virulence of pathogens in microgravity.
      Health status of astronauts might potentially benefit from maintaining a healthy
      microbiome by specifically managing their diet on space in addition to probiotic
      therapies. This review focuses on the current knowledge/understanding of how
      spaceflight affects human immunity and microbiome. 

PMID- 25970038
TI  - Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked
      Gold Quantum Clusters.
AB  - Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one
      clinical tool for cancer treatment and follow-up. While the surface plasmon
      effect of gold nanorods and nanoparticles has been effective for cancer therapy,
      their emission properties when compared to gold nanoclusters are weak for
      fluorescence imaging guided PDT. In order to address the above issues, we have
      synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid
      (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction
      property by incorporating a tumor-targeting agent (folic acid) and a
      photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum
      cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when
      compared to that of the photosensitizer alone (63%). PFL-AuC having 60 MUg (0.136
      mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population.
      Effective destruction of tumor cells was evident from the histopathology and
      fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC. 

PMID- 25970040
TI  - Rational Organization of Lanthanide-Based SMM Dimers into Three-Dimensional
      Networks.
AB  - Optimization of the reaction of [Ln(hfac)3].2H2O and pyridine-N-oxide (PyNO),
      which is known to afford double-bridged dimers, leads to triple-bridged dimers of
      formula [(Ln(hfac)3)2(PyNO)3] (Ln = Gd (1), Dy (2)) from which the Dy derivative
      (2) behaves as a single-molecule magnet (SMM). The pseudo threefold axis symmetry
      of this zero-dimensional building block makes possible its extension into a
      tridimensional network. By changing PyNO for 4,4'-bipyridine N,N'-dioxide
      (4,4'BipyNO) a tridimensional compound of formula {[Ln(hfac)3]2(4,4'BipyNO)2]}
      (Ln = Eu (3), Gd (4), and Dy (5)) is then rationally obtained. This covalent
      three-dimensional (3D) network has a remarkably high cell volume (V = 24 419
      A(3)) and is an arrangement of interpenetrated 3D subnetworks whose triple
      bridged dimers still behave as SMMs. 

PMID- 25970039
TI  - Structure-activity relationships of lysophosphatidylserine analogs as agonists of
      G-protein-coupled receptors GPR34, P2Y10, and GPR174.
AB  - Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by
      hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening
      of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS-specific
      human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with
      previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we
      examined the structure-activity relationships of a series of synthetic LysoPS
      analogues toward these recently deorphanized LysoPS receptors, based on the idea
      that LysoPS can be regarded as consisting of distinct modules (fatty acid,
      glycerol, and l-serine) connected by phosphodiester and ester linkages. Starting
      from the endogenous ligand (1-oleoyl-LysoPS, 1), we optimized the structure of
      each module and the ester linkage. Accordingly, we identified some structural
      requirements of each module for potency and for receptor subtype selectivity.
      Further assembly of individually structure-optimized modules yielded a series of
      potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and
      GPR174. 

PMID- 25970041
TI  - Effects of Two Different Rhodiola rosea Extracts on Primary Human Visceral
      Adipocytes.
AB  - Rhodiola rosea (Rro) has been reported to have various pharmacological
      properties, including anti-fatigue, anti-stress and anti-inflammatory activity.
      It is also known to improve glucose and lipid metabolism, but the effects of
      Rhodiola rosea on adipocyte differentiation and metabolism are not still
      elucidated. In this study the anti-adipogenic and lipolytic activity of two
      extracts of Rhodiola rosea, containing 3% salidroside (RS) or 1% salidroside and
      3% rosavines (RR) on primary human visceral adipocytes was investigated. Pre
      adipocytes were analyzed after 10 and 20 days of treatment during differentiation
      and after 7 days of treatment when they reached mature shape. The RS extract
      significantly induced higher apoptosis and lipolysis in comparison to control
      cells and to RR extract. In contrast, RR extract significantly reduced
      triglyceride incorporation during maturation. Differentiation of pre-adipocytes
      in the presence of RS and RR extracts showed a significant decrease in expression
      of genes involved in adipocyte function such as SLC2A4 and the adipogenic factor
      FGF2 and significant increase in expression of genes involved in inhibition of
      adipogenesis, such as GATA3, WNT3A, WNT10B. Furthermore RR extract, in contrast
      to RS, significantly down-regulates PPARG, the master regulator of adipogenesis
      and FABP4. These data support the lipolytic and anti-adipogenetic activity of two
      different commercial extracts of Rhodiola rosea in primary human visceral pre
      adipocytes during differentiation. 

PMID- 25970042
TI  - A Mild Catalytic Oxidation System: FePcOTf/H2O2 Applied for Cyclohexene
      Dihydroxylation.
AB  - Iron (III) phthalocyanine complexes were employed for the first time as a mild
      and efficient Lewis acid catalyst in the selective oxidation of cyclohexene to
      cyclohexane-1,2-diol. It was found that the catalyst FePcOTf shown excellent
      conversion and moderate selectivity relative to other iron (III) phthalocyanine
      complexes. The optimum conditions of the oxidation reaction catalyzed by
      FePcOTf/H2O2 have been researched in this paper. Iron (III) phthalocyanine
      triflate (1 mol %) as catalyst, hydrogen peroxide as oxidant, methanol as
      solvent, and a mole ratio of substrate and oxidant (H2O2) of 1:1 were used for
      achieving moderate yields of 1,2-diols under reflux conditions after eight hours.

PMID- 25970043
TI  - Assessing the Chemical Composition and Antimicrobial Activity of Essential Oils
      from Brazilian Plants-Eremanthus erythropappus (Asteraceae), Plectrantuns
      barbatus, and P. amboinicus (Lamiaceae).
AB  - The chemical composition and antimicrobial activity of essential oils obtained
      from three Brazilian plant species-leaves and branches of Eremanthus
      erythropappus (Asteraceae), leaves of Plectranthus barbatus, and leaves of P.
      amboinicus (Lamiaceae)-were determined. Analysis by GC/MS and determination of
      Kovats indexes both indicated delta-elemene (leaves-42.61% and branches-23.41%)
      as well as (-)-alpha-bisabolol (leaves-24.80% and stem bark-66.16%) as major
      constituents of E. erythropappus essential oils. The main components of leaves of
      P. barbatus were identified as (Z)-caryophyllene (17.98%), germacrene D (17.35%),
      and viridiflorol (14.13%); whereas those of leaves of P. amboinicus were
      characterized as p-cymene (12.01%), gamma-terpinene (14.74%), carvacrol (37.70%),
      and (Z)-caryophyllene (14.07%). The antimicrobial activity against yeasts and
      bacteria was assessed in broth microdilution assays to determine the minimum
      inhibitory concentration (MIC) necessary to inhibit microbial growth. In
      addition, the crude oil of branches of E. erythropappus was subjected to
      chromatographic separation procedures to afford purified (-)-alpha-bisabolol.
      This compound displayed biological activity against pathogenic yeasts, thus
      suggesting that the antimicrobial effect observed with crude oils of E.
      erythropappus leaves and branches may be related to the occurrence of (-)-alpha
      bisabolol as their main component. Our results showed that crude oils of
      Brazilian plants, specifically E. erythropappus, P. barbatus, and P. amboinicus
      and its components, could be used as a tool for the developing novel and more
      efficacious antimicrobial agents. 

PMID- 25970045
TI  - Prion 2015 oral abstracts.

PMID- 25970044
TI  - Mixed diacetylene/octadecyl melamine nanowires formed at the air/water interface
      exhibit unique structural and colorimetric properties.
AB  - Polydiacetylene (PDA) assemblies exhibit interesting photophysical properties,
      specifically, visible colorimetric transformations. A considerable body of work
      has focused on the formation and characterization of PDA Langmuir monolayer
      systems, and the overwhelming majority of reports so far have indicated that the
      adoption of 2D sheetlike structures associated with a hydrogen bond network
      between the diacetylene headgroups is a prerequisite for polymerization and
      chromatic properties. Here we report for the first time on the assembly of
      nanowire networks in mixed Langmuir monolayers comprising diacetylene monomers
      and octadecyl melamine surfactants. Structural and physical analysis indicates
      that the nanowires are composed of a helical organization of stacked
      diacetylene/octadecyl melamine building blocks assembled through hydrogen bonds
      between the melamine residues and the carboxylic termini of the diacetylenes.
      Following ultraviolet-induced polymerization, the PDA/octadecyl melamine
      nanowires exhibited unusual chromatic properties, specifically, an absence of the
      ubiquitous "blue" phase, rather transforming into a new "purple" PDA phase. This
      study demonstrates that the incorporation of surfactant constituents within
      diacetylene frameworks provides a means for modulating the structural and
      chromatic features of PDA assemblies, giving rise to new morphologies and unique
      optical properties. 

PMID- 25970046
TI  - Prion 2015 poster abstracts.

PMID- 25970047
TI  - Predicting the naming of regular-, irregular- and non-phonetic compounds in
      Chinese.
AB  - This study investigated the contributions of different cognitive measures in
      predicting the three types of Chinese characters: regular phonetic compounds,
      irregular phonetic compounds and non-phonetic compounds. A total of 246 Grade 3
      children (mean age = 8.63 yrs) were tested using a bunch of tasks including
      phonological processing, orthographic processing, morphological processing, rapid
      automatised naming and Chinese character naming. Results showed that advanced
      phonological processing skills contributed largely to regular phonetic compounds
      naming while other cognitive measures predict the naming of the other two types
      of characters. The results imply that the skills underlying the learning of
      regular phonetic compounds are different from that of irregular phonetic
      compounds and non-phonetic compounds, which are similar. Data from three poor
      readers whose performances pattern on naming different types of Chinese
      characters agreed with the pattern predicted by their performances in different
      cognitive tasks provide further support to the claim. Theoretical and pedagogical
      implications were discussed. 

PMID- 25970048
TI  - Computational Study of the Rate Coefficients for the Reactions of NO2 with
      CH3NHNH, CH3NNH2, and CH2NHNH2.
AB  - The reactions of NO2 with cis-/trans-CH3NHNH, CH3NNH2 and CH2NHNH2 have been
      studied theoretically by quantum chemical calculations and steady-state
      unimolecular master equation analysis based on RRKM theory. The barrier heights
      for the roaming transition states between nitro (RNO2) and nitrite (RONO)
      isomerization reactions and those for the concerted HONO and HNO2 elimination
      reactions from RNO2 and RONO, affect the pressure dependences of the product
      specific rate coefficients. At ambient temperature and pressure, the dominant
      product of the reactions of NO2 with cis-/trans-CH3NHNH and CH2NHNH2 would be
      expected to be HONO with trans-CH3NNH and CH2NNH2, respectively, whereas it is
      CH3N(NH2)NO2 for CH3NNH2 + NO2. The product-specific rate coefficients for the
      titled and related reactions on the same potential energy surfaces were proposed
      for kinetics modeling. 

PMID- 25970049
TI  - The $2.6 billion pill--methodologic and policy considerations.

PMID- 25970051
TI  - Clinical practice. Acute appendicitis--appendectomy or the "antibiotics first"
      strategy.

PMID- 25970052
TI  - Images in clinical medicine. Intraoral malignant melanoma.

PMID- 25970053
TI  - Case records of the Massachusetts General Hospital. Case 15-2015. A 27-year-old
      man with a nail in the eye.

PMID- 25970054
TI  - Mutation-specific T cells for immunotherapy of gliomas.

PMID- 25970055
TI  - Understanding bias--the case for careful study.

PMID- 25970050
TI  - Randomized trial of TAS-102 for refractory metastatic colorectal cancer.
AB  - BACKGROUND: Early clinical trials conducted primarily in Japan have shown that
      TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride,
      was effective in the treatment of refractory colorectal cancer. We conducted a
      phase 3 trial to further assess the efficacy and safety of TAS-102 in a global
      population of such patients. METHODS: In this double-blind study, we randomly
      assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo. The primary
      end point was overall survival. RESULTS: The median overall survival improved
      from 5.3 months with placebo to 7.1 months with TAS-102, and the hazard ratio for
      death in the TAS-102 group versus the placebo group was 0.68 (95% confidence
      interval [CI], 0.58 to 0.81; P<0.001). The most frequently observed clinically
      significant adverse events associated with TAS-102 were neutropenia, which
      occurred in 38% of those treated, and leukopenia, which occurred in 21%; 4% of
      the patients who received TAS-102 had febrile neutropenia, and one death related
      to TAS-102 was reported. The median time to worsening performance status (a
      change in Eastern Cooperative Oncology Group performance status [on a scale of 0
      to 5, with 0 indicating no symptoms and higher numbers indicating increasing
      degrees of disability] from 0 or 1 to 2 or more) was 5.7 months with TAS-102
      versus 4.0 months with placebo (hazard ratio, 0.66; 95% CI, 0.56 to 0.78;
      P<0.001). CONCLUSIONS: In patients with refractory colorectal cancer, TAS-102, as
      compared with placebo, was associated with a significant improvement in overall
      survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE
      ClinicalTrials.gov number, NCT01607957.).

PMID- 25970056
TI  - Treatment of HER2-positive metastatic breast cancer.

PMID- 25970057
TI  - Treatment of HER2-positive metastatic breast cancer.

PMID- 25970058
TI  - A device to narrow the coronary sinus for angina.

PMID- 25970059
TI  - A device to narrow the coronary sinus for angina.

PMID- 25970060
TI  - A device to narrow the coronary sinus for angina.

PMID- 25970061
TI  - A device to narrow the coronary sinus for angina.

PMID- 25970062
TI  - A device to narrow the coronary sinus for angina.

PMID- 25970063
TI  - Acid-base problems in diabetic ketoacidosis.

PMID- 25970064
TI  - Acid-base problems in diabetic ketoacidosis.

PMID- 25970065
TI  - Acid-base problems in diabetic ketoacidosis.

PMID- 25970066
TI  - Acid-base problems in diabetic ketoacidosis.

PMID- 25970067
TI  - More on Sweet's syndrome in patients with MDS and MEFV mutations.

PMID- 25970068
TI  - More on Sweet's syndrome in patients with MDS and MEFV mutations.

PMID- 25970069
TI  - More on Sweet's syndrome in patients with MDS and MEFV mutations.

PMID- 25970070
TI  - The cost of drug development.

PMID- 25970071
TI  - Images in clinical medicine. Radiation recall and woody fibrosis.

PMID- 25970072
TI  - Spiegelmer Inhibition of MCP-1/CCR2--Potential as an Adjunct Immunosuppressive
      Therapy in Transplantation.
AB  - The rejection process remains the key unsolved issue after transplantation of
      disparate tissue. The CC chemokine monocyte chemoattractant protein-1 (MCP
      1/CCL2) has been reported to be involved in the process of alloimmune
      interaction. Spiegelmers are l-oligonucleotides that can be designed to bind to
      pharmacologically relevant target molecules. Here, we tested a high-affinity
      Spiegelmer-based MCP-1 inhibitor (mNOX-E36) in an allogeneic heart transplant
      model. Fully vascularized allogeneic heterotopic heart transplantations from
      BALB/c to C57BL/6 mice were performed. Mice were either treated with the anti-MCP
      1-Spiegelmer (mNOX-E36) in monotherapy or in combination with subtherapeutic
      doses of cyclosporine A (CsA) (10 mg/kgBW/day) for 10 days. Controls received
      equivalent doses of a non-functional Spiegelmer (revmNOX-E36). Graft survival of
      allogeneic heart transplants was slightly but significantly prolonged under mNOX
      E36 monotherapy (median graft survival 10 day +/- 0.7) compared to revmNOX-E36
      (median graft survival 7 day +/- 0.3; P = 0.001). A synergistic beneficial effect
      could be seen when mNOX-E36 was administered in combination with subtherapeutic
      doses of CsA (18 day +/- 2.8 versus 7 day +/- 0.3; P < 0.0001). Levels of
      inflammatory cytokines and 'alarmins' were significantly reduced, and the number
      of F4/80(+) cells was lower under combination therapy (1.8% +/- 1.3%; versus
      14.6% +/- 4.4%; P = 0.0002). This novel inhibitor of the MCP-1/CCR2 axis (mNOX
      E36), which has already proven efficacy and tolerability in early clinical
      trials, alleviates acute rejection processes in allogeneic transplantation
      especially when combined with subtherapeutic doses of CsA. Thus, mNOX-E36 may
      have potential as an adjunct immunomodulatory agent.

PMID- 25970073
TI  - Biosurfactants in cosmetics and biopharmaceuticals.
AB  - Biosurfactants are surface-active biomolecules that are produced by various micro
      organisms. They show unique properties i.e. lower toxicity, higher
      biodegradability and environmental compatibility compared to their chemical
      counterparts. Glycolipids and lipopeptides have prompted application in
      biotechnology and cosmetics due to their multi-functional profile i.e.
      detergency, emulsifying, foaming and skin hydrating properties. Additionally,
      some of them can be served as antimicrobials. In this study the current status of
      research and development on rhamnolipids, sophorolipids, mannosyloerythritol
      lipids, trehalipids, xylolipids and lipopeptides particularly their commercial
      application in cosmetics and biopharmaceuticals, is described. 

PMID- 25970074
TI  - An Australian cohort of 210 patients with multiple invasive squamous cell
      carcinomas: risk factors and associated increased risk of melanoma and internal
      malignancies.
AB  - BACKGROUND: Patients with a history of non-melanoma skin cancer (NMSC) have a 50%
      risk of developing subsequent NMSC.(13) Currently there are limited data on the
      association between multiple squamous cell carcinomas (SCC) and the risk of other
      cancers, including melanomas. OBJECTIVE: To assess the risk factors in a cohort
      of 210 Australians with a history of multiple invasive SCC, focusing on the
      association between multiple SCC and other cancers. METHODS: Data were collected
      from patients of a private practice in south-east Queensland. RESULTS: A fair
      complexion and childhood sun exposure were found to be common in this cohort.
      Approximately half the patients who had their first SCC at or before the age of
      30 years subsequently developed a melanoma. There was also an increased risk of
      internal cancer, prostate cancer being the commonest, followed by bowel and
      breast cancer. CONCLUSION: Patients with a history of multiple invasive SCC
      should be aware of their increased risk of future NMSC and of melanomas. The
      results of thisstudy suggest such patients and their care providers should also
      consider an appropriate screening for internal malignancies.

PMID- 25970076
TI  - Intragenus competition between coccolithoviruses: an insight on how a select few
      can come to dominate many.
AB  - Viruses are a major cause of coccolithophore bloom demise in both temperate and
      sub-temperate oceanic regions. Most infection studies on coccolithoviruses have
      been conducted with a single virus strain, and the effect of intragenus
      competition by closely related coccolithoviruses has been ignored. Here we
      conducted combined infection experiments, infecting Emiliania huxleyi CCMP 2090
      with two coccolithoviruses: EhV-86 and EhV-207 both simultaneously and
      independently. EhV-207 displayed a shorter lytic cycle and increased production
      potential than EhV-86 and was remarkably superior under competitive conditions.
      Although the viruses displayed identical adsorption kinetics in the first 2 h
      post infection, EhV-207 gained a numerical advantage as early as 8 h post
      infection. Quantitative polymerase chain reaction (PCR) revealed that when
      infecting in combination, EhV-207 was not affected by the presence of EhV-86,
      whereas EhV-86 was quickly out-competed, and a significant reduction in free and
      cell-associated EhV-86 was seen as early as 2 days after the initial infection.
      The observation of such clear phenotypic differences between genetically
      distinct, yet similar, coccolithovirus strains, by flow cytometry and
      quantitative real-time PCR allowed tentative links to the burgeoning genomic,
      transcriptomic and metabolic data to be made and the factors driving their
      selection, in particular to the de novo coccolithovirus-encoded sphingolipid
      biosynthesis pathway. This work illustrates that, even within a family, not all
      viruses are created equally, and the potential exists for relatively small
      genetic changes to infer disproportionately large competitive advantages for one
      coccolithovirus over another, ultimately leading to a few viruses dominating the
      many.

PMID- 25970075
TI  - Toxic epidermal necrolysis induced by methazolamide in a Chinese-Korean man
      carrying HLA-B*59:01.
AB  - BACKGROUND: Methazolamide is used to lower intraocular pressure in patients with
      glaucoma. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      associated with methazolamide treatment have been diagnosed in Korean, Japanese,
      and Japanese-American patients. According to recent research, the human leukocyte
      antigen (HLA) allele HLA-B*59:01 is strongly linked to SJS/TEN associated with
      methazolamide treatment. OBJECTIVE: A patient of Chinese-Korean ethnicity was
      diagnosed with TEN associated with methazolamide treatment. The purpose of this
      study was to examine the potential genetic basis of this disease. METHODS: A
      polymerase chain reaction sequence-specific primer (PCR-SSP) typing system was
      used to genotype this patient's peripheral blood DNA for HLA-B*59. RESULTS: The
      genotype HLA-B*59:01 was detected in the patient. CONCLUSIONS: This study
      demonstrates the genotype of HLA-B*59:01 in a patient with TEN associated with
      methazolamide treatment and thus supports the possible correlation between
      genetic background and methazolamide-associated SJS/TEN.

PMID- 25970077
TI  - Collective Contexts in Conversation: Grounding by Proxy.
AB  - Anecdotal evidence suggests that participants in conversation can sometimes act
      as a coalition. This implies a level of conversational organization in which
      groups of individuals form a coherent unit. This paper investigates the
      implications of this phenomenon for psycholinguistic and semantic models of
      shared context in dialog. We present a corpus study of multiparty dialog which
      shows that, in certain circumstances, people with different levels of overt
      involvement in a conversation, that is, one responding and one not, can
      nonetheless access the same shared context. We argue that contemporary models of
      shared context need to be adapted to capture this situation. To address this, we
      propose "grounding by proxy," in which one person can respond on behalf of
      another, as a simple mechanism by which shared context can accumulate for a
      coalition as a whole. We explore this hypothesis experimentally by investigating
      how people in a task-oriented coalition respond when their shared context appears
      to be weakened. The results provide evidence that, by default, coalition members
      act on each other's behalf, and when this fails they work to compensate. We
      conclude that this points to the need for a new concept of collective grounding
      acts and a corresponding concept of collective contexts in psycholinguistic and
      semantic models of dialog. 

PMID- 25970078
TI  - Photorheological ionic liquids.
AB  - Two room temperature ionic liquids (ILs) bearing coumarin and p-hydroxycinnamic
      acid moieties are synthesized, and their photochemistry is studied in solution
      and neat conditions. Irradiation at absorption maxima leads to photochemical
      transformations and results in changes of their rheological properties which are
      evaluated by rotational rheometry. Samples of ionic liquids are also studied by
      Hyper-Rayleigh scattering, and the effect of their photochemistry on ionic
      nanoaggregation is discussed. 

PMID- 25970079
TI  - Octopus-like suction cups: from natural to artificial solutions.
AB  - Octopus suckers are able to attach to all nonporous surfaces and generate a very
      strong attachment force. The well-known attachment features of this animal result
      from the softness of the sucker tissues and the surface morphology of the portion
      of the sucker that is in contact with objects or substrates. Unlike artificial
      suction cups, octopus suckers are characterized by a series of radial grooves
      that increase the area subjected to pressure reduction during attachment. In this
      study, we constructed artificial suction cups with different surface geometries
      and tested their attachment performances using a pull-off setup. First, smooth
      suction cups were obtained for casting; then, sucker surfaces were engraved with
      a laser cutter. As expected, for all the tested cases, the engraving treatment
      enhanced the attachment performance of the elastomeric suction cups compared with
      that of the smooth versions. Moreover, the results indicated that the surface
      geometry with the best attachment performance was the geometry most similar to
      octopus sucker morphology. The results obtained in this work can be utilized to
      design artificial suction cups with higher wet attachment performance. 

PMID- 25970080
TI  - Peripheral blood stem cell transplantation improves liver functional reserve.
AB  - BACKGROUND: Currently available treatment options for decompensated hepatitis B
      induced liver cirrhosis are limited and largely ineffective. Recently, stem cell
      transplantation has emerged as a promising treatment for cirrhosis. The aim of
      this study was to determine whether autologous peripheral blood stem cell
      transplantation can improve liver functional reserve in patients with hepatitis B
      induced cirrhosis. MATERIAL/METHODS: In this study, 51 patients with hepatitis B
      induced liver cirrhosis were assigned to the treatment group (n=23) or the
      control group (n=28). The treatment group underwent autologous peripheral blood
      stem cell transplantation in addition to comprehensive medical treatment, and the
      control group received comprehensive medical treatment alone. Liver functional
      reserve was monitored for 48 weeks after autologous peripheral blood stem cell
      transplantation. RESULTS: After transplantation, most patients showed
      improvements in symptoms such as fatigue, anorexia, and abdominal distension. The
      retention rate of indocyanine green at 15 minutes, a common indicator of liver
      functional reserve, declined from 41.99+/-4.68 at baseline to 37.79+/-3.75 by 48
      weeks after transplantation, showing significant improvement. CONCLUSIONS:
      Autologous peripheral blood stem cell transplantation can improve several markers
      of liver health and liver functional reserve and is a promising prospect for
      clinical application.

PMID- 25970081
TI  - Monitoring the impact of cow's milk allergy on children and their families with
      the FLIP questionnaire--a six-month follow-up study.
AB  - BACKGROUND: Many children with cow's milk allergy (CMA) develop tolerance, but,
      challenges in daily life may remain. Using the Food hypersensitivity famiLy
      ImPact questionnaire (FLIP), we sought to monitor changes in the impact of CMA
      over time. METHODS: Families of children with CMA, who participated in the
      validation of the FLIP, were re-approached 6 months later for follow-up. Change
      in reported difficulties was assessed by paired sample t-test and mixed models,
      stratifying by outgrown vs. persistent CMA. RESULTS: Impact on families with
      children who had outgrown CMA (n = 20) decreased in the FLIP's total score (p =
      0.0001) and in two subscales; Health and Emotions (p = 0.0001) and Everyday Life
      (p = 0.0001). In contrast, no significant improvements were registered in
      nutritional concerns. Impact on the group with persistent CMA (n = 57) was
      unchanged at follow-up except for more impact on Everyday Life (p = 0.001). In
      the final analysis comparing longitudinal changes in the groups, the strongest
      differences were observed for the subscales Health & Emotions and Everyday Life;
      for the Nutrition subscale, the between-group changes also differed, but to
      lesser extent. CONCLUSIONS: We have documented the varying impact of CMA on
      parents and children over time. Families who were still affected continued to
      experience impact in daily life. Despite development of tolerance, families who
      were no longer affected revealed continuing nutritional concerns. Follow-ups
      should be offered even after outgrown CMA to encourage progression to
      unrestricted diet, to prevent eating disorders and to promote healthy growth.

PMID- 25970082
TI  - Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2
      probe.
AB  - Cyclooxygenase-2 (COX-2) is a promising target for the imaging of cancer in a
      range of diagnostic and therapeutic settings. We report a near-infrared COX-2
      targeted probe, fluorocoxib C (FC), for visualization of solid tumors by optical
      imaging. FC exhibits selective and potent COX-2 inhibition in both purified
      protein and human cancercell lines. In vivo optical imaging shows selective
      accumulation of FC in COX-2-overexpressing human tumor xenografts [1483 head and
      neck squamous cell carcinoma (HNSCC)] implanted in nude mice, while minimal
      uptake is detectable in COX-2-negative tumor xenografts (HCT116)or 1483 HNSCC
      xenografts preblocked with the COX-2-selective inhibitor celecoxib. Time course
      imaging studies conducted from 3 h to 7-day post-FC injection revealed a marked
      reduction in nonspecific fluorescent signals with retention of fluorescence in
      1483 HNSCC tumors. Thus, use of FC in a delayed imaging protocol offers an
      approach to improve imaging signal-to-noise that should improve cancer detection
      in multiple preclinical and clinical settings.

PMID- 25970083
TI  - Fluorescence molecular tomography reconstruction via discrete cosine transform
      based regularization.
AB  - Fluorescence molecular tomography (FMT) as a noninvasive imaging modality has
      been widely used for biomedical preclinical applications. However, FMT
      reconstruction suffers from severe ill-posedness, especially when a limited
      number of projections are used. In order to improve the quality of FMT
      reconstruction results, a discrete cosine transform (DCT) based reweighted L1
      norm regularization algorithm is proposed. In each iteration of the
      reconstruction process, different reweighted regularization parameters are
      adaptively assigned according to the values of DCT coefficients to suppress the
      reconstruction noise. In addition, the permission region of the reconstructed
      fluorophores is adaptively constructed to increase the convergence speed. In
      order to evaluate the performance of the proposed algorithm, physical phantom and
      in vivo mouse experiments with a limited number of projections are carried out.
      For comparison, different L1-norm regularization strategies are employed. By
      quantifying the signal-to-noise ratio (SNR) of the reconstruction results in the
      phantom and in vivo mouse experiments with four projections, the proposed DCT
      based reweighted L1-norm regularization shows higher SNR than other L1-norm
      regularizations employed in this work.

PMID- 25970084
TI  - Odontological light-emitting diode light-curing unit beam quality.
AB  - The distribution of light intensity of three light-curing units (LCUs) to cure
      the resin-based composite for dental fillings was analyzed, and a homogeneity
      index [flat-top factor (FTF)] was calculated. The index is based on the M2 index,
      which is used for laser beams. An optical spectrum analyzer was used with an
      optical fiber to produce an x-y power profile of each LCU light guide. The FTF
      calculated values were 0.51 for LCU1 and 0.55 for LCU2, which was the best FTF,
      although it still differed greatly from the perfect FTF = 1, and 0.27 for LCU3,
      which was the poorest value and even lower than the Gaussian FTF = 0.5. All LCUs
      presented notably heterogeneous light distribution, which can lead professionals
      and researchers to produce samples with irregular polymerization and poor
      mechanical properties.

PMID- 25970085
TI  - Single-side access, isotropic resolution, and multispectral three-dimensional
      photoacoustic imaging with rotate-translate scanning of ultrasonic detector
      array.
AB  - Photoacoustic imaging can achieve high-resolution three-dimensional (3-D)
      visualization of optical absorbers at penetration depths of ~1 cm in biological
      tissues by detecting optically induced high ultrasound frequencies. Tomographic
      acquisition with ultrasound linear arrays offers an easy implementation of single
      side access, parallelized, and high-frequency detection, but usually comes with
      an image quality impaired by the directionality of the detectors. Indeed, a
      simple translation of the array perpendicular to its median imaging plane is
      often used, but results both in a poor resolution in the translation direction
      and strong limited-view artifacts.To improve the spatial resolution and the
      visibility of complex structures while retaining a planar detection geometry, we
      introduce, in this paper, a rotate-translate scanning scheme and investigate the
      performance ofa scanner implemented at 15 MHz center frequency. The developed
      system achieved a quasi-isotropic uniform 3-D resolution of ~170 MUm over a cubic
      volume of side length 8.5 mm, i.e., an improvement in the resolution in the
      translation direction by almost one order of magnitude. Dual-wavelength imaging
      was also demonstrated with ultrafast wavelength shifting. The validity of our
      approach was shown in vitro. We discuss the ability to enable in vivo imaging for
      preclinical and clinical studies.

PMID- 25970086
TI  - Using Telehealth to Enable Patient-Centered Care for Liver Transplantation.

PMID- 25970087
TI  - Coherent regulation in yeast's cell-cycle network.
AB  - We define a measure of coherent activity for gene regulatory networks, a property
      that reflects the unity of purpose between the regulatory agents with a common
      target. We propose that such harmonious regulatory action is desirable under a
      demand for energy efficiency and may be selected for under evolutionary
      pressures. We consider two recent models of the cell-cycle regulatory network of
      the yeast, Saccharomyces cerevisiae as a case study and calculate their degree of
      coherence. A comparison with random networks of similar size and composition
      reveals that the yeast's cell-cycle regulation is wired to yield an exceptionally
      high level of coherent regulatory activity. We also investigate the mean degree
      of coherence as a function of the network size, connectivity and the fraction of
      repressory/activatory interactions. 

PMID- 25970088
TI  - Position statement from the Chromosome Abnormality Screening Committee on behalf
      of the Board of the International Society for Prenatal Diagnosis.

PMID- 25970089
TI  - The Larger Linear N-Heteroacenes.
AB  - The close structural and chemical relationship of N-heteroacenes to pentacene
      suggests their broad applicability in organic electronic devices, such as thin
      film transistors. The superb materials science properties of azaacenes result
      from their improved resistance toward oxidation and their potential for electron
      transport, both of which have been demonstrated recently. The introduction of
      nitrogen atoms into the aromatic perimeter of acenes stabilizes their frontier
      molecular orbitals and increases their electron affinity. The HOMO-LUMO gaps in
      azaacenes in which the nitrogen atoms are symmetrically placed are similar to
      those of the acenes. The judiciously placed nitrogen atoms induce an "umpolung"
      of the electronic behavior of these pentacene-like molecules, i.e., instead of
      hole mobility in thin-film transistors, azaacenes are electron-transporting
      materials. The fundamental synthetic approaches toward larger azaacenes are
      described and discussed. Several synthetic methodologies have been exploited, and
      some have been newly developed to assemble substituted azaacenes. The oldest
      methods are condensation-based. Aromatic o-diamines are coupled with o
      dihydroxyarenes in the melt without solvent. This method works well for
      unsubstituted azaacenes only. The attachment of substituents to the starting
      materials renders these "fire and sword" methods less useful. The starting
      materials decompose under these conditions. The direct condensation of
      substituted o-diamines with o-quinones proceeds well in some cases. Fluorinated
      benzene rings next to a pyrazine unit are introduced by nucleophilic aromatic
      substitution employing hexafluorobenzene. However, with these well-established
      synthetic methodologies, a number of azaacene topologies cannot be synthesized.
      The Pd-catalyzed coupling of aromatic halides and aromatic diamines has therefore
      emerged as versatile tool for azaacene synthesis. Now substituted diaza- and
      tetraazaacenes, azapentacenes, azahexacenes, and azaheptacenes are accessible. Pd
      catalysis-based coupling methods for both activated and nonactivated o-dihalides
      have been developed. The larger azaacene representatives were unknown before but
      are of conceptual and theoretical interest. Azaacenes, particularly the
      symmetrical bis(triisopropylsilylethynyl)-substituted tetraazapentacene, are
      primarily used in organic field-effect transistors, but smaller azaacenes shine
      in the field as organic light-emitting diode (OLED) emitters. Diazatetracenes and
      substituted benzoquinoxalines are successful, improving electron injection and
      increasing OLED brightness, as compared to that of pure tetracenes. On the basis
      of the acene framework, nitrogen atoms in the acene perimeter and aggregation
      precluding molecular appendages create solid-state fluorescent species. Azaacenes
      are expanding the range and complementing the purview of acenes in organic
      electronic applications. They enlarge the profiles of acenes with respect to
      synthetic strategies, structures, properties, and applications. 

PMID- 25970090
TI  - Change in the Prevalence of HIV-1 and the Rate of Transmitted Drug-Resistant HIV
      1 in Haiphong, Northern Vietnam.
AB  - We previously reported a significant decrease in HIV-1 prevalence, with no
      increase in drug-resistant HIV-1 among injecting drug users (IDU), female sex
      workers (FSW), and blood donors (BD), in Haiphong, Vietnam, from 2007 to 2009. In
      2012, 388 IDU, 51 FSW, and 200 BD were recruited for further analysis. None had a
      history of antiretroviral treatment. From 2007 to 2012, HIV-1 prevalence was
      reduced from 35.9% to 18.6% (p<0.001), 23.1% to 9.8% (p<0.05), and 2.9% to 1%
      (p=0.29) in IDU, FSW, and BD, respectively. Of 79 anti-HIV-1 antibody-positive
      samples, 61 were successfully analyzed for the pol-reverse transcriptase (RT)
      region. All HIV-1 strains were CRF01_AE. Nonnucleoside RT inhibitor-resistant
      mutations, Y181C/I, were detected in three subjects; one had the nucleoside RT
      inhibitor-resistant mutations L74V and M184V and one had E138K. The prevalence of
      transmitted drug-resistant HIV-1 in Haiphong increased slightly from 1.8% in 2007
      to 6.6% in 2012 (p=0.06).

PMID- 25970092
TI  - Novel protein-repellent and biofilm-repellent orthodontic cement containing 2
      methacryloyloxyethyl phosphorylcholine.
AB  - The objectives of this study were to develop the first protein-repellent resin
      modified glass ionomer cement (RMGI) by incorporating 2-methacryloyloxyethyl
      phosphorylcholine (MPC) for orthodontic applications, and to investigate the MPC
      effects on protein adsorption, biofilm growth, and enamel bond strength. MPC was
      incorporated into RMGI at 0% (control), 1.5%, 3%, and 5% by mass. Specimens were
      stored in water at 37 degrees C for 1 and 30 days. Enamel shear bond strength
      (SBS) was measured, and the adhesive remnant index (ARI) scores were assessed.
      Protein adsorption onto the specimens was determined by a micro bicinchoninic
      acid method. A dental plaque microcosm biofilm model with human saliva as
      inoculum was used. The results showed that adding 3% of MPC into RMGI did not
      significantly reduce the SBS (p > 0.1). There was no significant loss in SBS for
      RMGI containing 3% MPC after water-aging for 30 days, as compared to 1 day (p >
      0.1). RMGI with 3% MPC had protein adsorption that was 1/10 that of control. RMGI
      with 3% MPC greatly reduced the bacterial adhesion, and lactic acid production
      and colony-forming units of biofilms, while substantially increasing the medium
      solution pH containing biofilms. The protein-repellent and biofilm-repellent
      effects were not decreased after water-aging for 30 days. In conclusion, the MPC
      containing RMGI is promising to reduce biofilms and white spot lesions without
      compromising orthodontic bracket-enamel bond strength. The novel protein
      repellent method may have applicability to other orthodontic cements, dental
      composites, adhesives, sealants, and cements to repel proteins and biofilms. (c)
      2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 949
      959, 2016.

PMID- 25970091
TI  - Effects of particulate matter exposure on blood 5-hydroxymethylation: results
      from the Beijing truck driver air pollution study.
AB  - Previous studies have reported epigenetic changes induced by environmental
      exposures. However, previous investigations did not distinguish 5-methylcytosine
      (5mC) from a similar oxidative form with opposite functions, 5
      hydroxymethylcytosine (5hmC). Here, we measured blood DNA global 5mC and 5hmC by
      ELISA and used adjusted mixed-effects regression models to evaluate the effects
      of ambient PM10 and personal PM2.5 and its elemental components-black carbon
      (BC), aluminum (Al), calcium (Ca), potassium (K), iron (Fe), sulfur (S), silicon
      (Si), titanium (Ti), and zinc (Zn)-on blood global 5mC and 5hmC levels. The study
      was conducted in 60 truck drivers and 60 office workers in Beijing, China from
      The Beijing Truck Driver Air Pollution Study at 2 exams separated by one to 2
      weeks. Blood 5hmC level (0.08%) was ~83-fold lower than 5mC (6.61%). An inter
      quartile range (IQR) increase in same-day PM10 was associated with increases in
      5hmC of 26.1% in office workers (P = 0.004), 20.2% in truck drivers (P = 0.014),
      and 21.9% in all participants combined (P < 0.001). PM10 effects on 5hmC were
      increasingly stronger when averaged over 4, 7, and 14 d preceding assessment (up
      to 132.6% for the 14-d average in all participants, P < 0.001). PM10 effects were
      also significant after controlling for multiple testing (family-wise error rate;
      FWER < 0.05). 5hmC was not correlated with personal measures of PM2.5 and
      elemental components (FWER > 0.05). 5mC showed no correlations with PM10, PM2.5,
      and elemental components measures (FWER > 0.05). Our study suggests that exposure
      to ambient PM10 affects 5hmC over time, but not 5mC. This finding demonstrates
      the need to differentiate 5hmC and 5mC in environmental studies of DNA
      methylation.

PMID- 25970094
TI  - Spurious decrease in the WBC count measured by the WNR channel of XN haematology
      analyser (Sysmex) could be associated with metastatic adenocarcinoma.

PMID- 25970093
TI  - A comparison of the folding characteristics of free and ribosome-tethered
      polypeptide chains using limited proteolysis and mass spectrometry.
AB  - The kinetics and thermodynamics of protein folding are commonly studied in vitro
      by denaturing/renaturing intact protein sequences. How these folding mechanisms
      relate to de novo folding that occurs as the nascent polypeptide emerges from the
      ribosome is much less well understood. Here, we have employed limited proteolysis
      followed by mass spectrometry analyses to compare directly free and ribosome
      tethered polypeptide chains of the Src-homology 3 (SH3) domain and its unfolded
      variant, SH3-m10. The disordered variant was found to undergo faster proteolysis
      than SH3. Furthermore, the trypsin cleavage patterns observed show minor, but
      significant, differences for the free and ribosome-bound nascent chains, with
      significantly fewer tryptic peptides detected in the presence of ribosome. The
      results highlight the utility of limited proteolysis coupled with mass
      spectrometry for the structural analysis of these complex systems, and pave the
      way for detailed future analyses by combining this technique with chemical
      labeling methods (for example, hydrogen-deuterium exchange, photochemical
      oxidation) to analyze protein folding in real time, including in the presence of
      additional ribosome-associated factors. 

PMID- 25970095
TI  - Basic principles to consider when opening a nurse practitioner-owned practice in
      Texas.
AB  - PURPOSE: Advanced Practice Registered Nurse (APRN)-owned clinics in Texas are
      becoming more common and because of the success of these early clinics, more
      APRNs are considering opening their own practice; but Texas remains one of the
      most restrictive states for APRN practice and many questions remain. What are the
      regulations about physician delegation? Will you get reimbursed from insurance
      companies and at what rates? Can you be a primary care provider (PCP)? DATA
      SOURCES: Changes enacted after the adoption of Senate Bill 406 improved the
      opportunities for APRNs in Texas yet several requirements must be met and early
      consultation with a lawyer and accountant can facilitate the initial business
      setup. The Prescriptive Authority Agreement simplified the delegation
      requirements and allows the APRN increased flexibility in obtaining and
      consulting with a delegating physician. Becoming credentialed as a PCP with
      private insurance companies is often complicated; however, utilizing the Council
      for Affordable Quality Healthcare's Universal Provider Data source for initial
      credentialing can facilitate this. CONCLUSIONS AND IMPLICATION FOR PRACTICE:
      Although this article does not discuss the financial implications of opening a
      practice, it does cover many aspects including legislative and regulatory
      requirements for practice, credentialing process and challenges, business
      structure, and tax implications.

PMID- 25970096
TI  - Chitosan encapsulation modulates the effect of capsaicin on the tight junctions
      of MDCK cells.
AB  - Capsaicin has known pharmacological effects including the ability to reversibly
      open cellular tight junctions, among others. The aim of this study was to develop
      a strategy to enhance the paracellular transport of a substance with low
      permeability (FITC-dextran) across an epithelial cell monolayer via reversible
      opening of cellular tight junctions using a nanosystem comprised by capsaicin and
      of chitosan. We compared the biophysical properties of free capsaicin and
      capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards
      epithelial MDCK-C7 cells and their effect on the integrity of tight junctions,
      membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7
      cells to capsaicin at a concentration of 500 MUM, which was evident for the free
      compound, is not observable following its encapsulation. The interaction between
      nanocapsules and the tight junctions of MDCK-C7 cells was investigated by
      impedance spectroscopy, digital holographic microscopy and structured
      illumination fluorescence microscopy. The nanocapsules modulated the interaction
      between capsaicin and tight junctions as shown by the different time profile of
      trans-epithelial electrical resistance and the enhanced permeability of
      monolayers incubated with FITC-dextran. Structured illumination fluorescence
      microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The
      capsaicin-loaded nanocapsules could be further developed as drug nanocarriers
      with enhanced epithelial permeability.

PMID- 25970097
TI  - Mechanistic insights into a novel chromone-appended Cu(II) anticancer drug
      entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity
      against MCF-7 and HepG2 cancer cells.
AB  - A new chromone-appended Cu(ii) drug entity () was designed and synthesized as a
      potential anticancer chemotherapeutic agent. The structural elucidation was
      carried out thoroughly by elemental analysis, FT-IR, EPR, ESI-MS and single
      crystal X-ray crystallography. Complex resulted from the in situ methoxylation
      reaction of the 3-formylchromone ligand and its subsequent complexation with the
      copper nitrate salt in a 2 : 1 ratio, respectively. crystallized in the
      monoclinic P21/c space group possessing the lattice parameters, a = 8.75 A, b =
      5.07 A, c = 26.22 A, alpha = gamma = 90 degrees , beta = 96.3 degrees  per unit
      cell. Furthermore, in vitro interaction studies of with ct-DNA and tRNA were
      carried out which suggested more avid binding propensity towards the RNA target
      via intercalative mode, which was reflected from its Kb, K and Ksv values. The
      gel electrophoretic mobility assay was carried out on the pBR322 plasmid DNA
      substrate, to ascertain the cleaving ability and the mechanistic pathway in the
      presence of additives, and the results revealed the efficient cleaving ability of
      via the oxidative pathway. In vitro cell growth inhibition via the MTT assay was
      carried out to evaluate the cytotoxicity of complex and IC50 values were found to
      be in the range of 5-10 MUg mL(-1) in HepG2 and MCF-7 cancer cell lines, which
      were found to be much lower than the IC50 values of previously reported similar
      Cu(ii) complexes. Additionally, in the presence of , reactive oxygen species
      (ROS) and thiobarbituric acid reactive substance (TBARS) levels in the tested
      cancer cell lines increased significantly, coupled with reduced glutathione (GSH)
      levels. Thus, our results suggested that ROS plays an important role in cell
      apoptosis induced by the Cu(ii) complex and validates its potential to act as a
      robust anticancer drug entity. 

PMID- 25970098
TI  - Birth-cohort trends in older-age functional disability and their relationship
      with socio-economic status: Evidence from a pooling of repeated cross-sectional
      population-based studies for the UK.
AB  - We examine birth-cohort trends behind recent changes in the prevalence of
      functional disability in the older population living in private households in the
      United Kingdom (UK). By using three different socio-economic indicators available
      in the nationally representative cross-sectional data on older individuals
      interviewed between 2002 and 2012 in the Family Resource Survey (FRS) (96,733
      respondents), we investigate the extent to which the overall trends have been
      more favourable among more advantaged than disadvantaged socioeconomic groups.
      Compared to the cohort of people born in 1924, successive cohorts of older men
      have lower odds of having at least one functional difficulty (FD), whereas no
      significant trend was found for women. Among people with at least one FD,
      however, the number of disabilities increases for each successive cohort of older
      women (incidence rate ratio 1.027, 95% confidence interval 1.023 to 1.031, P <
      0.001) and men (incidence rate ratio 1.028, 95% confidence interval 1.024 to
      1.033, P < 0.001). By allowing interactions between birth cohort and SES
      indicators, a significant increasing cohort trend in the number of reported FDs
      was found among older men and women at lower SES, whereas an almost stable
      pattern was observed at high SES. Our results suggest that the overall slightly
      increasing birth-cohort trend in functional difficulties observed among current
      cohorts of older people in the UK hides underlying increases among low SES
      individuals and a relative small reduction among high SES individuals. Further
      studies are needed to understand the causes of such trends and to propose
      appropriate interventions. However, if the SES differentials in trends in FDs
      observed in the past continue, this could have important implications for the
      future costs of the public system of care and support for people with care needs.

PMID- 25970099
TI  - Systematic review and meta-analysis of isolated posterior fossa malformations on
      prenatal ultrasound imaging (part 1): nomenclature, diagnostic accuracy and
      associated anomalies.
AB  - OBJECTIVE: To explore the outcome in fetuses with prenatal diagnosis of posterior
      fossa anomalies apparently isolated on ultrasound imaging. METHODS: MEDLINE and
      EMBASE were searched electronically utilizing combinations of relevant medical
      subject headings for 'posterior fossa' and 'outcome'. The posterior fossa
      anomalies analyzed were Dandy-Walker malformation (DWM), mega cisterna magna
      (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes
      observed were rate of chromosomal abnormalities, additional anomalies detected at
      prenatal magnetic resonance imaging (MRI), additional anomalies detected at
      postnatal imaging and concordance between prenatal and postnatal diagnoses. Only
      isolated cases of posterior fossa anomalies - defined as having no cerebral or
      extracerebral additional anomalies detected on ultrasound examination - were
      included in the analysis. Quality assessment of the included studies was
      performed using the Newcastle-Ottawa Scale for cohort studies. We used meta
      analyses of proportions to combine data and fixed- or random-effects models
      according to the heterogeneity of the results. RESULTS: Twenty-two studies
      including 531 fetuses with posterior fossa anomalies were included in this
      systematic review. The prevalence of chromosomal abnormalities in fetuses with
      isolated DWM was 16.3% (95% CI, 8.7-25.7%). The prevalence of additional central
      nervous system (CNS) abnormalities that were missed at ultrasound examination and
      detected only at prenatal MRI was 13.7% (95% CI, 0.2-42.6%), and the prevalence
      of additional CNS anomalies that were missed at prenatal imaging and detected
      only after birth was 18.2% (95% CI, 6.2-34.6%). Prenatal diagnosis was not
      confirmed after birth in 28.2% (95% CI, 8.5-53.9%) of cases. MCM was not
      significantly associated with additional anomalies detected at prenatal MRI or
      detected after birth. Prenatal diagnosis was not confirmed postnatally in 7.1%
      (95% CI, 2.3-14.5%) of cases. The rate of chromosomal anomalies in fetuses with
      isolated BPC was 5.2% (95% CI, 0.9-12.7%) and there was no associated CNS anomaly
      detected at prenatal MRI or only after birth. Prenatal diagnosis of BPC was not
      confirmed after birth in 9.8% (95% CI, 2.9-20.1%) of cases. The rate of
      chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI, 0.8-17.1%)
      and there were no additional anomalies detected at prenatal MRI (0% (95% CI, 0.0
      45.9%)). The proportions of cerebral anomalies detected only after birth was
      14.2% (95% CI, 2.9-31.9%). Prenatal diagnosis was not confirmed after birth in
      32.4% (95% CI, 18.3-48.4%) of cases. CONCLUSIONS: DWM apparently isolated on
      ultrasound imaging is a condition with a high risk for chromosomal and associated
      structural anomalies. Isolated MCM and BPC have a low risk for aneuploidy or
      associated structural anomalies. The small number of cases with isolated VH
      prevents robust conclusions regarding their management from being drawn.
      Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 25970101
TI  - Ebselen as a potent covalent inhibitor of New Delhi metallo-beta-lactamase (NDM
      1).
AB  - We report the discovery of a promising NDM-1 inhibitor, ebselen, through a cell
      based screening approach. Enzymatic kinetic study and ESI-MS analysis suggested
      that ebselen could bind to NDM-1 by forming a S-Se bond with the Cys(221) residue
      at the active site, thereby exhibiting a new inhibition mechanism with broad
      spectrum inhibitory potential. 

PMID- 25970102
TI  - Breast health beliefs, behaviors, and barriers among latina permanent resident
      and migratory farm workers.
AB  - There is a dearth of research on the breast health behaviors of migratory farm
      workers. This research used focus group methodology to compare the breast cancer
      beliefs and barriers of Latina women working as migratory farmers (n = 33) and
      permanent residents (n = 31). In comparison to their permanent resident
      counterparts, migrant farmers had low knowledge about the causes of breast
      cancer, and experienced significant barriers to care. Many barriers were cultural
      specific, including culturally-based gender roles. These findings have
      significant implications for designing culturally-relevant interventions to
      improve access to care among this population. 

PMID- 25970100
TI  - Both PIGA and PIGL mutations cause GPI-a deficient isolates in the Tk6 cell line.
AB  - Molecular analysis of proaerolysin selected glycosylphosphatidylinositol anchor
      (GPI-a) deficient isolates in the TK6 cell line was performed. Initial studies
      found that the expected X-linked PIGA mutations were rare among the spontaneous
      isolates but did increase modestly after ethyl methane sulfate (EMS) treatment
      (but to only 50% of isolates). To determine the molecular bases of the remaining
      GPI-a deficient isolates, real-time analysis for all the 25 autosomal GPI-a
      pathway genes was performed on the isolates without PIGA mutations, determining
      that PIGL mRNA was absent for many. Further analysis determined these isolates
      had several different homozygous deletions of the 5' region of PIGL (17p12-p22)
      extending 5' (telomeric) through NCOR1 and some into the TTC19 gene (total
      deletion >250,000 bp). It was determined that the TK6 parent had a hemizygous
      deletion in 17p12-p22 (275,712 bp) extending from PIGL intron 2 into TTC19 intron
      7. Second hit deletions in the other allele in the GPI-a deficient isolates led
      to the detected homozygous deletions. Several of the deletion breakpoints
      including the original first hit deletion were sequenced. As strong support for
      TK6 having a deletion, a number of the isolates without PIGA mutations nor
      homozygous PIGL deletions had point mutations in the PIGL gene. These studies
      show that the GPI-a mutation studies using TK6 cell line could be a valuable
      assay detecting point and deletion mutations in two genes simultaneously.

PMID- 25970103
TI  - Connecting teens to caring adults in a school-based health center: a case study.
AB  - The traditional medical care system is generally unable to provide the broad
      health and wellness services needed by many adolescents, especially those from
      low-income and racial/ethnic minority communities. Using a theoretical framework
      adapted from Bronfenbrenner's ecological model of multiple influencers, this case
      study examined how a school-based health center was able to provide a network of
      connections for adolescents to caring adults within the school and the local
      community. Contributors to this network were the creation of a student-centered
      community with access to adolescent-friendly services, providers acting as
      connectors, and care of the whole adolescent. 

PMID- 25970104
TI  - Illuminance, Subjective Sleep Quality, and Psychosomatic Health in Elderly
      Individuals Requiring Care: A Survey of Japan's Hokuriku Region in Winter.
AB  - We measured the illuminance exposure for 3 days in winter of a convenience sample
      of 44 elderly people certified as requiring support in Japan's Hokuriku region.
      We calculated the illuminance ratio per minute during activity and while in bed
      and analyzed the relationship between illuminance, subjective sleep quality, and
      psychosomatic health. There was a significant negative correlation between
      illuminance and 15-item Geriatric Depression Scale scores. Multiple regression
      analysis indicated that depression scores were significantly related to age,
      level of required support, and illuminance. The findings suggest that
      environments without light and dark cycles increase depression scores in frail
      elderly people. 

PMID- 25970105
TI  - Community health nursing advocacy: a concept analysis.
AB  - The purpose of this article is to present an in-depth analysis of the concept of
      community health nursing (CHN) advocacy. Walker and Avant's (2010) 8-step concept
      analysis methodology was used. A broad inquiry into the literature between 1994
      and 2014 resulted in the identification of the uses, defining attributes,
      empirical referents, antecedents, and consequences, as well as the articulation
      of an operational definition of CHN advocacy. Model and contrary cases were
      identified to demonstrate the concept's application and to clarify its meaning.
      This analysis contributes to the advancement of knowledge of CHN advocacy and
      provides nurse clinicians, educators, and researchers with some conceptual
      clarity to help improve community health outcomes. 

PMID- 25970108
TI  - Enhancing the quality of clinical nursing care.

PMID- 25970109
TI  - Bordetella pertussis is an uncommon pathogen in children hospitalized with
      bronchiolitis during the winter season.
AB  - BACKGROUND: In the United States (U.S.), Bordetella pertussis incidence has
      increased. Cough and apnea are common findings in pertussis and also in
      bronchiolitis, the most common cause of hospitalization in U.S. infants. The
      objective was to determine the prevalence of B. pertussis infection in children
      hospitalized with bronchiolitis and to describe its clinical course. METHODS:
      Children hospitalized with bronchiolitis and age <2 years were eligible for a
      prospective, multicenter cohort study during 3 consecutive winter seasons
      (November-March) from 2007 to 2010. Sixteen sites in 12 states participated using
      a standardized enrollment protocol. Families were asked the 2010 Centers for
      Disease Control and Prevention pertussis classification questions. Nasopharyngeal
      aspirates were obtained and tested by real-time polymerase chain reaction for 16
      viruses, Mycoplasma pneumoniae and B. pertussis. RESULTS: Two thousand sixty
      eight (94%) of 2207 children had 1 or more respiratory pathogens. B. pertussis
      was identified in 4 children [0.2%; 95% confidence interval (CI): 0.1-0.5%] with
      3 having a viral co-infection. All 4 were younger than 4 months; 2 met the
      Centers for Disease Control and Prevention definition of probable pertussis; and
      3 had received at least 1 dose of an acellular pertussis vaccine. During the
      hospitalization, 2 had paroxysmal cough, 1 required intensive care unit care and
      the median length of stay was 13 days. CONCLUSIONS: Our data support that B.
      pertussis is an uncommon pathogen in U.S. children hospitalized with
      bronchiolitis in the winter. Making a diagnosis of pertussis can be challenging
      because the disease can be atypical and may not meet the Centers for Disease
      Control and Prevention definition of probable infection.

PMID- 25970110
TI  - Hemophagocytic lymphohistiocytosis in children with visceral leishmaniasis.
AB  - Acquired hemophagocytic lymphohistiocitosis (HLH) syndrome can be a complication
      of visceral leishmaniasis (VL). A multicenter prospective study was conducted to
      determine the frequency of HLH syndrome in children with VL. Twenty-four children
      with VL were identified, and 10 (41%) developed HLH syndrome. VL should be ruled
      out in all children with HLH criteria living in or coming from endemic areas. 

PMID- 25970111
TI  - Chronic meningococcemia presenting as a recurrent painful rash without fever in a
      teenage girl.
AB  - Chronic meningococcemia is a rare diagnosis seen in patients with recurrent fever
      and rash. We describe a case of chronic meningococcemia in a teenage girl who
      presented with a recurrent painful rash, without fever, over a period of 8 weeks.

PMID- 25970112
TI  - Phlyctenular conjunctivitis and tuberculosis.

PMID- 25970113
TI  - Multidrug-resistant Acinetobacter baumannii bacteremia treated with tigecycline
      in two pediatric burn patients.

PMID- 25970114
TI  - Fatal rabies case did not die "accidentally" and should not be considered a
      rabies survivor.

PMID- 25970115
TI  - The "Milwaukee protocol" for treatment of human rabies is no longer valid.

PMID- 25970116
TI  - Pentoxifylline therapy for late-onset sepsis in preterm infants: a randomized
      controlled trial.
AB  - BACKGROUND: The role of pentoxifylline (PTX) in reducing mortality associated
      with neonatal sepsis is not well established. We aimed to assess the efficacy and
      safety of PTX as an adjunct to antibiotics on mortality and morbidity in preterm
      infants with late-onset sepsis (LOS). METHODS: Double blind, randomized
      controlled trial was conducted on 120 preterm infants with LOS. They were
      randomly assigned to receive either intravenous PTX 5 mg/kg/hr for 6 hours on 6
      successive days or placebo. Death before hospital discharge was our primary
      outcome and secondary outcomes were length of hospital stay, duration of
      respiratory support, duration of antibiotics use, short-term morbidity of preterm
      infants, tumor necrosis factor-alpha concentrations, C-reactive protein
      concentrations, and adverse effects of PTX. RESULTS: A total of 120 infants were
      enrolled, 60 in each group, 78 (65%) infants had confirmed and 42 (35%) had
      suspected LOS. There were no significant differences between groups regarding
      mortality [6 (10%) in PTX vs. 10 (16.5%) in placebo, P = 0.44], short-term
      morbidity and combined mortality and/or short-term morbidity [18 (30%) vs. 24
      (40%), P = 0.23]. PTX therapy was associated with significant reduction of serum
      tumor necrosis factor-alpha and C-reactive protein concentrations. The length of
      hospital stay, durations of respiratory support and antibiotic therapy were
      significantly shorter in the PTX group. Patients in PTX group had less need for
      vasopressors, lower incidence of metabolic acidosis, disseminated intravascular
      coagulopathy and thrombocytopenia. No adverse effects to PTX were reported.
      CONCLUSIONS: PTX has a beneficial adjuvant effect to antibiotic therapy in
      preterm infants with LOS without significant impact on neonatal mortality and
      morbidity.

PMID- 25970117
TI  - Prevalence and incidence of liver dysfunction and assessment of biomarkers of
      liver disease in HIV-infected Asian children.
AB  - BACKGROUND: We determined the prevalence and incidence of liver dysfunction
      before and after initiation of combination antiretroviral therapy (cART) in the
      TREAT Asia Pediatric HIV Observational Database. METHODS: Data from children
      initiated on cART between 2 and 18 years of age with baseline alanine
      aminotransferase (ALT) available before and at least once after cART initiation
      in TREAT Asia Pediatric HIV Observational Database between 2008 and 2012 were
      analyzed. Prevalence and incidence of liver dysfunction and biomarkers including
      the aspartate aminotransferase to platelet ratio index and FIB4 index (a
      noninvasive panel to stage liver disease) were assessed. RESULTS: Data from 1930
      children were included. Their median age was 6.9 years; 49% were male; 98% were
      perinatally infected and 94% were initiated on non-nucleoside reverse
      transcriptase-based cART regimens. Before cART, the prevalence of ALT >=3 times
      the upper limit of normal (*ULN) was 5.8%. There were 8.5% of children with
      aspartate aminotransferase to platelet ratio index >1.5 (suggestive of liver
      fibrosis) and 2.7% with FIB4 index >1.3 (predictive of possible cirrhosis). Among
      the 1143 cases with normal baseline ALT (<=1*ULN), the incidence of ALT 3*ULN
      after cART was 1.19 of 1000 person-months (95% confidence interval: 0.93-1.51).
      Two of 350 with available tests (0.6%) met Hy's law (ALT >3*ULN and total
      bilirubin >2*ULN). By multivariate analysis, baseline hemoglobin <7.5 g/dL was a
      predictor of ALT >3*ULN, whereas age 5-9 years at cART initiation was protective
      for liver dysfunction. CONCLUSIONS: We demonstrated a low prevalence and
      incidence of liver dysfunction before and after cART initiation in children with
      normal baseline chemistries. In this population facing life-long cART,
      prospective surveillance for emergence of liver disease is warranted.

PMID- 25970118
TI  - Effect of targeted estrogen delivery using glucagon-like peptide-1 on insulin
      secretion, insulin sensitivity and glucose homeostasis.
AB  - The female estrogen 17beta-estradiol (E2) enhances pancreatic beta-cell function
      via estrogen receptors (ERs). However, the risk of hormone dependent cancer
      precludes the use of general estrogen therapy as a chronic treatment for
      diabetes. To target E2 to beta-cells without the undesirable effects of general
      estrogen therapy, we created fusion peptides combining active or inactive
      glucagon-like peptide-1 (GLP-1) and E2 in a single molecule (aGLP1-E2 and iGLP1
      E2 respectively). By combining the activities of GLP-1 and E2, we envisioned
      synergistic insulinotropic activities of these molecules on beta-cells. In
      cultured human islets and in C57BL/6 mice, both aGLP1 and aGLP1-E2 enhanced
      glucose-stimulated insulin secretion (GSIS) compared to vehicle and iGLP1-E2
      without superior efficacy of aGLP1-E2 compared to GLP-1 alone. However, aGLP1-E2
      decreased fasting and fed blood glucose to a greater extent than aGLP1 and iGLP1
      E2 alone. Further, aGLP1-E2 exhibited improved insulin sensitivity compared to
      aGLP1 and iGLP1-E2 alone (HOMA-IR and insulin tolerance test). In conclusion,
      targeted estrogen delivery to non-diabetic islets in the presence of GLP-1 does
      not enhance GSIS. However, combining GLP-1 to estrogen delivers additional
      efficacy relative to GLP-1 alone on insulin sensitivity and glucose homeostasis
      in non-diabetic mice. 

PMID- 25970119
TI  - [Current epidemiology of tuberculosis in Germany].
AB  - BACKGROUND: In addition to malaria and HIV/AIDS, tuberculosis (TB) is one of the
      world's most important infectious diseases. Also in Germany tuberculosis still
      remains a relevant public health problem that needs special attention.
      OBJECTIVES: This article provides an overview of the tuberculosis epidemiology in
      Germany with emphasis on drug resistance and population groups that are
      predominantly affected. METHODS: Based on surveillance data provided in the
      notification system, the TB-situation in Germany is presented-particularly with
      respect to drug resistance, origin of patients (country of birth and nationality)
      and treatment outcome. RESULTS: Since 2009, the continuous decline in case
      numbers has slowed down and is now stagnating as observed in several other
      industrialized nations. Since 2007, the proportion of foreign-born patients has
      continuously increased and accounts for over half of all cases registered in
      Germany. Special attention deserves the current drug resistance situation: With a
      proportion of 3.4% in 2013, multidrug-resistant tuberculosis (MDR-TB) has
      increased significantly compared to the previous year (2.1%) and the rate is
      therefore higher than in many other European low-incidence countries.
      Particularly high levels of MDR-TB were observed among foreign-born patients
      originating from a former Soviet Union country. On average, treatment success was
      observed in 79% of the cases. Thus, Germany does not reach the WHO target of 85%
      treatment success. Stagnating case numbers together with the observed drug
      resistance trend clearly indicate the need for continued efforts in tuberculosis
      control in Germany including focused strategies for the most affected population
      groups.

PMID- 25970120
TI  - [Current Issues Arising from Tuberculosis Screening with Interferon-Gamma-Release
      Assays (IGRAs)].
AB  - A positive IGRA test does not always indicate a latent tuberculosis infection
      (LTBI); the prevalence of LTBI in the tested collective must be carefully
      considered in test interpretation. When IGRAs are performed repeatedly in
      healthcare workers (BiG), variabilities of test results (conversions and
      reversions of the respective previous negative or positive result) can be
      expected. Therefore only individuals for whom there is an established risk of
      being infected by Mycobacterium tuberculosis (M.tb.), i.e. significantly
      prolonged direct exposure to an infectious TB case, should be tested. Positive
      IGRA results alone do not reliably predict subsequent progression to active TB
      disease. According to the current body of scientific knowledge, IGRAs are not
      superior to the tuberculin skin test (TST) in the case of young children.

PMID- 25970121
TI  - [Current microbiological methods in the investigation of mycobacteria].
AB  - The rapid and reliable detection of tuberculosis is the main goal of
      microbiological analyses. This is not only of great value for an early diagnosis
      and early start of an adequate therapy, but also helps to stop transmission and
      spread of the disease. Prerequisites for successful detection of mycobacteria are
      careful selection of patient specimens, proper sampling and appropriate shipping.
      In addition to the classical microbiological methods such as staining for acid
      fast bacteria and culture procedures, newer molecular methods are gaining greater
      importance (PCR; NAT). TB bacteria and resistance-associated mutations can be
      detected from the specimens directly, providing an early hint about resistant
      strains. In positive cultures, M. tuberculosis complex and nontuberculous
      mycobacteria must be discriminated from each other. Drug susceptibility testing
      (DST) of all first-line drugs has to be performed from one isolate of each
      patient and repeated if TB bacteria are still isolated after 2 months of therapy.
      DST of second-line drugs should follow in case of drug resistance or drug
      intolerance.

PMID- 25970122
TI  - [New Drugs for the Treatment of Multidrug-resistant Tuberculosis (MDR-TB)].
AB  - This article summarizes the state of development of new drugs for the treatment
      of multidrug-resistant tuberculosis. We focused on delamanid, bedaquiline,
      pretomanid, SQ 109 and sutezolid. 

PMID- 25970123
TI  - [Non Tuberculous Mycobacteria--a Short Review about Epidemiology, Diagnosis and
      Treatment].
AB  - Non tuberculous mycobacterial diseases are caused by mycobacteria other than M.
      tuberculosis complex. NTM are found in the environment and are not transmitted
      from humans to humans. Infection occurs by the inhalation of dust or aerosols.
      The finding of NTM is not equal to a diagnosis of active disease. For the
      diagnosis of active disease well defined clinical and microbiological criteria
      have to be fulfilled. Gold standard is the detection of NTM by culture, in the
      case of pulmonary NTM at least two times. There is no established susceptibility
      testing. Treatment mostly consists of three drugs, given for up to 24 months.

PMID- 25970124
TI  - [In Process Citation].

PMID- 25970125
TI  - [In Process Citation].

PMID- 25970127
TI  - Next-Generation Lithium Metal Anode Engineering via Atomic Layer Deposition.
AB  - Lithium metal is considered to be the most promising anode for next-generation
      batteries due to its high energy density of 3840 mAh g(-1). However, the extreme
      reactivity of the Li surface can induce parasitic reactions with solvents,
      contamination, and shuttled active species in the electrolyte, reducing the
      performance of batteries employing Li metal anodes. One promising solution to
      this issue is application of thin chemical protection layers to the Li metal
      surface. Using a custom-made ultrahigh vacuum integrated deposition and
      characterization system, we demonstrate atomic layer deposition (ALD) of
      protection layers directly on Li metal with exquisite thickness control. We
      demonstrate as a proof-of-concept that a 14 nm thick ALD Al2O3 layer can protect
      the Li surface from corrosion due to atmosphere, sulfur, and electrolyte
      exposure. Using Li-S battery cells as a test system, we demonstrate an improved
      capacity retention using ALD-protected anodes over cells assembled with bare Li
      metal anodes for up to 100 cycles. 

PMID- 25970128
TI  - Synchronous microencapsulation of multiple components in silymarin into PLGA
      nanoparticles by an emulsification/solvent evaporation method.
AB  - The development of polymeric carriers loaded with extracts suffers from the
      drawback not to be able to incorporate simultaneously various pharmacological
      compounds into the formulation. The aim of this study was therefore to achieve
      synchronous microencapsulation of multiple components of silymarin into poly
      (lactic-co-glycolic acid) nanoparticle, the most commonly used polymeric carrier
      with biodegradability and safety. The main strategy taken was to improve the
      overall entrapment efficiency and to reduce the escaping ratio of the components
      of different physicochemical properties. The optimized nanoparticles were
      spherical in morphology with a mean particle size of 150 +/- 5 nm. Under common
      preparative conditions, silybin and isosilybin were entrapped in high efficiency,
      whereas taxifolin, silychristin and silydianin, especially taxifolin, showed less
      entrapment because they were more hydrophilic. By changing the pH of the outer
      aqueous phase and saturating it with silymarin, the entrapment efficiency of
      taxifolin, silychristin and silydianin could be significantly improved to over
      90%, the level similar to silybin and isosilybin, thereby achieving synchronous
      encapsulation. It could be concluded that synchronous encapsulation of multiple
      components of silymarin was achieved by optimizing the preparative variables. 

PMID- 25970129
TI  - Inherited metabolic disorders: Quality management for laboratory diagnosis.
AB  - BACKGROUND: The advancements in laboratory technology and knowledge of the
      mechanisms behind metabolic disorders have facilitated accurate and reliable
      laboratory testing in screening, diagnosis and treatment of inherited metabolic
      disorders. Therefore, quality assurance and improvement in diagnostic proficiency
      have become essential in this area. In most developing countries, standard
      practices for quality assurance in testing of enzymes, hormones and metabolites
      involved in these genetic disorders have not been fully implemented. We highlight
      the benefits of quality assurance and aim to create awareness for greater
      compliance with the criteria established for quality control to ensure accuracy
      in biochemical genetic testing. METHODS: Establishing the limit of detection and
      testing range for each analyte and enzyme are useful as a reference while setting
      up new assays. To minimize error, %CV should be monitored regularly. Evaluation
      of proficiency testing performance provides scope to the laboratory for improving
      testing quality. RESULTS: Low precision seen in lysosomal enzyme assays does not
      undermine their diagnostic efficacy as differentiation between patients and
      normal subjects is possible by setting % coefficient of variation cutoffs.
      CONCLUSIONS: The study will facilitate the collaboration with other screening and
      diagnostic systems and help in development of new laboratory standards.

PMID- 25970130
TI  - Glycosaminoglycans in Tendon Physiology, Pathophysiology, and Therapy.
AB  - Although glycosaminoglycans constitute a minor portion of native tissues, they
      play a crucial role in various physiological processes, while their abnormal
      expression is associated with numerous pathophysiologies. Glycosaminoglycans have
      become increasingly prevalent in biomaterial design for tendon repair, given
      their low immunogenicity and their inherent capacity to stimulate the
      regenerative processes, while maintaining resident cell phenotype and function.
      Further, their incorporation into three-dimensional scaffold conformations
      significantly improves their mechanical properties, while reducing the formation
      of peritendinous adhesions. Herein, we discuss the role of glycosaminoglycans in
      tendon physiology and pathophysiology and the advancements achieved to date using
      glycosaminoglycan-functionalized scaffolds for tendon repair and regeneration. It
      is evidenced that glycosaminoglycan functionalization has led to many
      improvements in tendon tissue engineering and it is anticipated to play a pivotal
      role in future reparative therapies. 

PMID- 25970131
TI  - CO2 in the spotlight.

PMID- 25970132
TI  - Taming the TCR: antigen-specific immunotherapeutic agents for autoimmune
      diseases.
AB  - Current treatments for autoimmune diseases are typically non-specific anti
      inflammatory agents that affect not only the autoreactive cells but also the
      parts of the immune system that are required to maintain health. There is a need
      for the development of antigen-specific therapeutic agents that can effectively
      prevent the autoimmune attack while leaving the rest of the immune system
      functioning as normal. The simplest way to achieve this is using the autoantigen
      itself as a tolerizing agent; however, there is some risk involved with
      administering a potentially pathogenic antigen. In this review, we focus instead
      on the development and use of modified T cell receptor (TCR) ligands, in which
      the peptide ligand is modified to change the response by the T cell from a
      disease inducing to a protective response, and still retain the antigen
      specificity necessary to target the autoreactive T cells. We review the use of
      modified TCR ligands as therapeutic agents in animal models of autoimmunity and
      in human autoimmune disease, and finally consider how they need to be improved in
      order to use them effectively in patients with autoimmune disease. 

PMID- 25970133
TI  - Carbon Nitrogen Nanotubes as Efficient Bifunctional Electrocatalysts for Oxygen
      Reduction and Evolution Reactions.
AB  - Oxygen reduction and evolution reactions are essential for broad range of
      renewable energy technologies such as fuel cells, metal-air batteries and
      hydrogen production through water splitting, therefore, tremendous effort has
      been taken to develop excellent catalysts for these reactions. However, the
      development of cost-effective and efficient bifunctional catalysts for both
      reactions still remained a grand challenge. Herein, we report the
      electrocatalytic investigations of bamboo-shaped carbon nitrogen nanotubes
      (CNNTs) having different diameter distribution synthesized by liquid chemical
      vapor deposition technique using different nitrogen containing precursors. These
      CNNTs are found to be efficient bifunctional electrocatalyst for oxygen reduction
      and evolution reactions. The electrocatalytic activity strongly depends on the
      nanotube diameter as well as nitrogen functionality type. The higher diameter
      CNNTs are more favorable for these reactions. The increase in nanotube diameter
      itself enhances the catalytic activity by lowering the oxygen adsorption energy,
      better conductivity, and further facilitates the reaction by increasing the
      percentage of catalytically active nitrogen moieties in CNNTs. 

PMID- 25970134
TI  - Synthesis of Unsupported d(1)-d(x) Oxido-Bridged Heterobimetallic Complexes
      Containing V(IV): A New Direction for Metal-to-Metal Charge Transfer.
AB  - Heterobimetallic complexes composed only of first-row transition metals
      [(TMTAA)V(IV)?O->M(II)Py5Me2](OTf)2 (TMTAA = 7,16-dihydro-6,8,15,17
      tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine; Py5Me2 = 2,6-bis(1,1
      bis(2-pyridyl)ethyl)pyridine; M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II); OTf =
      trifluoromethanesulfonate) have been synthesized through a dative interaction
      between a terminal oxido and M(II) metal centers. This is the first series of
      V(IV)?O->M(II) heterobimetallic complexes containing an unsupported oxido bridge.
      Among these five complexes, only V(IV)?O->Fe(II) (3b) has a clear new absorption
      band upon formation of the dinuclear species (502 nm, epsilon = 1700 M(-1) cm(
      1)). This feature is assigned to a metal-to-metal charge transfer (MMCT)
      transition from V(IV) to Fe(II), which forms a V(V)-O-Fe(I) excited state. This
      assignment is supported by electrochemical data, electronic absorption profiles,
      and resonance Raman spectroscopy and represents the first report of visible-light
      induced MMCT in a heterobimetallic oxido-bridged molecule where the electron
      originates on a d(1) metal center. 

PMID- 25970136
TI  - Polymer-graphene oxide quadlayer thin-film assemblies with improved gas barrier.
AB  - Layer-by-layer assembly was used to create quadlayers (QLs) of chitosan (CH),
      poly(acrylic acid) (PAA), CH, and graphene oxide (GO). Electron microscopy
      confirmed GO coverage over the film and a highly ordered nanobrick wall
      structure. By varying pH deviation between CH and PAA, a thick and interdiffused
      polymer matrix was created because of the altered chain conformation. A 5 CH (pH
      5.5)/PAA (pH 3)/CH (pH 5.5)/GO QL assembly (48 nm) exhibits very low oxygen
      permeability (3.9 * 10(-20) cm(3) cm cm(-2) Pa(-1) s(-1)) that matches SiOx
      barrier coatings. In an effort to maintain barrier performance under high
      humidity, GO was thermally reduced to increase hydrophobicity of the film. This
      reduction step increased H2/CO2 selectivity of a 5 QL film from 5 to 215,
      exceeding Robeson's upper bound limit. This unique water-based multilayer
      nanocoating is very promising for a variety of gas purification and packaging
      applications. 

PMID- 25970135
TI  - Coilin: The first 25 years.
AB  - Initially identified as a marker of coiled bodies (now Cajal bodies or CBs), the
      protein coilin was discovered a quarter of century ago. Coilin is now known to
      scaffold the CB, but its structure and function are poorly understood. Nearly
      devoid of predicted structural motifs, coilin has numerous reported molecular
      interactions that must underlie its role in the formation and function of CBs. In
      this review, we summarize what we have learned in the past 25 years about
      coilin's structure, post-transcriptional modifications, and interactions with RNA
      and proteins. We show that genes with homology to human coilin are found in
      primitive metazoans and comment on differences among model organisms. Coilin's
      function in Cajal body formation and RNP metabolism will be discussed in the
      light of these developments.

PMID- 25970137
TI  - Bioengineering of the model lantibiotic nisin.
AB  - The lantibiotics are a class of bacterially produced antimicrobial peptides
      (bacteriocins) that contain several unusual amino acids resulting from enzyme
      mediated post-translational modifications. They exhibit high specific activity
      against Gram-positive targets, including many antibiotic-resistant pathogens, and
      consequently have been investigated with a view to their application as
      antimicrobials in both the food and medical arenas. Importantly, the gene-encoded
      nature of lantibiotics makes them more amenable to bioengineering strategies to
      further enhance their antimicrobial and physicochemical properties. However,
      although the bioengineering of lantibiotics has been underway for over 2 decades,
      significant progress has only been reported in recent years. This review charts
      recent developments with regard to the implementation of bioengineering
      strategies to enhance the functional characteristics of the prototypical and most
      studied lantibiotic nisin. 

PMID- 25970139
TI  - S...pi Chalcogen Bonds between SF2 or SF4 and C-C Multiple Bonds.
AB  - SF2 and SF4 were each paired with a series of unsaturated hydrocarbons including
      ethene, ethyne, 1,3-butadiene, and benzene, in each case forming a chalcogen bond
      between the S atom and the carbon pi-system. MP2 ab initio calculations reveal
      that the S atom is situated directly above one specific C?C bond, even when more
      than one are present. The binding energies range between 3.3 and 6.6 kcal/mol.
      SF2 engages in a stronger, and shorter, noncovalent bond than does SF4 for all
      systems with the exception of benzene, to which SF4 is more tightly bound. cis
      Butadiene complexes contain the shortest chalcogen bond, even if not necessarily
      the strongest. The internal S-F covalent bonds elongate upon formation of each
      chalcogen bond. The molecules are held together largely by charge transfer
      forces, particularly from the C?C pi-bonds to the sigma*(SF) antibonding
      orbitals. In the case of SF2, a sulfur lone pair can transfer charge into the pi*
      MOs of the alkene, a back-transfer which is more difficult for SF4. 

PMID- 25970138
TI  - Phonetic categorisation and cue weighting in adolescents with Specific Language
      Impairment (SLI).
AB  - This study investigates phonetic categorisation and cue weighting in adolescents
      and young adults with Specific Language Impairment (SLI). We manipulated two
      acoustic cues, vowel duration and F1 offset frequency, that signal word-final
      stop consonant voicing ([t] and [d]) in English. Ten individuals with SLI (14.0
      21.4 years), 10 age-matched controls (CA; 14.6-21.9 years) and 10 non-matched
      adult controls (23.3-36.0 years) labelled synthetic CVC non-words in an
      identification task. The results showed that the adolescents and young adults
      with SLI were less consistent than controls in the identification of the good
      category representatives. The group with SLI also assigned less weight to vowel
      duration than the adult controls. However, no direct relationship between
      phonetic categorisation, cue weighting and language skills was found. These
      findings indicate that some individuals with SLI have speech perception deficits
      but they are not necessarily associated with oral language skills. 

PMID- 25970140
TI  - A simple method for normalization of DNA extraction to improve the quantitative
      detection of soil-borne plant pathogenic oomycetes by real-time PCR.
AB  - Most of the current research into the quantification of soil-borne pathogenic
      oomycetes lacks determination of DNA extraction efficiency, probably leading to
      an incorrect estimation of DNA quantity. In this study, we developed a convenient
      method by using a 100 bp artificially synthesized DNA sequence derived from the
      mitochondrion NADH dehydrogenase subunit 2 gene of Thunnus thynnus as a control
      to determine the DNA extraction efficiency. The control DNA was added to soils
      and then co-extracted along with soil genomic DNA. DNA extraction efficiency was
      determined by the control DNA. Two different DNA extraction methods were compared
      and evaluated using different types of soils, and the commercial kit was proved
      to give more consistent results. We used the control DNA combined with real-time
      PCR to quantify the oomycete DNAs from 12 naturally infested soils. Detectable
      target DNA concentrations were three to five times higher after normalization.
      Our tests also showed that the extraction efficiencies varied on a sample-to
      sample basis and were <50%. Therefore, the method introduced here is simple and
      useful for the accurate quantification of soil-borne pathogenic oomycetes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Oomycetes include many important plant
      pathogens. Accurate quantification of these pathogens is essential in the
      management of diseases. This study reports an easy method utilizing an external
      DNA control for the normalization of DNA extraction by real-time PCR. By
      combining two different efficient soil DNA extraction methods, the developed
      quantification method dramatically improved the results. This study also proves
      that the developed normalization method is necessary and useful for the accurate
      quantification of soil-borne plant pathogenic oomycetes.

PMID- 25970141
TI  - Paradoxical simultaneous regression and progression of lesions in a phase II
      study of everolimus in classic Kaposi sarcoma.

PMID- 25970142
TI  - The Evolution of Tissue Stiffness at Radiofrequency Ablation Sites During Lesion
      Formation and in the Peri-Ablation Period.
AB  - INTRODUCTION: Elastography imaging can provide radiofrequency ablation (RFA)
      lesion assessment due to tissue stiffening at the ablation site. An important
      aspect of assessment is the spatial and temporal stability of the region of
      stiffness increase in the peri-ablation period. The aim of this study was to use
      2 ultrasound-based elastography techniques, shear wave elasticity imaging (SWEI)
      and acoustic radiation force impulse (ARFI) imaging, to monitor the evolution of
      tissue stiffness at ablation sites in the 30 minutes following lesion creation.
      METHODS AND RESULTS: In 6 canine subjects, SWEI measurements and 2-D ARFI images
      were acquired at 6 ventricular endocardial RFA sites before, during, and for 30
      minutes postablation. An immediate increase in tissue stiffness was detected
      during RFA, and the area of the postablation region of stiffness increase (RoSI)
      as well as the relative stiffness at the RoSI center was stable approximately 2
      minutes after ablation. Of note is the observation that relative stiffness in the
      region adjacent to the RoSI increased slightly during the first 15 minutes,
      consistent with local fluid displacement or edema. The magnitude of this
      increase, ~0.5-fold from baseline, was significantly less than the magnitude of
      the stiffness increase directly inside the RoSI, which was greater than 3-fold
      from baseline. CONCLUSIONS: Ultrasound-based SWEI and ARFI imaging detected an
      immediate increase in tissue stiffness during RFA, and the stability and
      magnitude of the stiffness change suggest that consistent elasticity-based lesion
      assessment is possible 2 minutes after and for at least 30 minutes following
      ablation.

PMID- 25970143
TI  - Comorbid depression/anxiety and teeth removed: Behavioral Risk Factor
      Surveillance System 2010.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      participants (i) who reported having had clinical diagnoses of depression and
      anxiety with 6+ teeth removed and (ii) who reported having had clinical diagnoses
      of depression and anxiety with edentulism. METHODS: The Behavioral Risk Factor
      Surveillance System (BRFSS) Survey 2010 was used for the study. Analyses involved
      using SAS 9.3(r) to determine variable frequencies, Rao-Scott chi-square
      bivariate analyses, and Proc Surveylogistic for the logistic regressions on
      complex survey designs. Participants eligibility included being 18 years or older
      and having complete data on depression, anxiety, and number of teeth removed.
      RESULTS: There were 76 292 eligible participants; 13.4% reported an anxiety
      diagnosis, 16.7% reported a depression diagnosis, and 8.6% reported comorbid
      depression and anxiety. The adjusted logistic regression models were significant
      for anxiety and depression alone and in combination for 6+ teeth removed (AOR:
      anxiety 1.23; 95% CI: 1.10, 1.38; P = 0.0773; AOR: depression 1.23; 95% CI: 1.10,
      1.37; P = 0.0275; P < 0.0001; and AOR: comorbid depression and anxiety 1.30; 95%
      CI: 1.14, 1.49; P = 0.0001). However, the adjusted models with edentulism as the
      outcome failed to reach significance. CONCLUSIONS: Comorbid depression and
      anxiety are associated independently with 6+ teeth removed compared with 0-5
      teeth removed in a national study conducted in United States. Comorbid depression
      and anxiety were not shown to be associated with edentulism as compared with any
      teeth present.

PMID- 25970144
TI  - Grey matter injury patterns in cerebral palsy: associations between structural
      involvement on MRI and clinical outcomes.
AB  - AIMS: In a population cohort of children with grey matter injury (GMI) and
      cerebral palsy (CP), we aimed to describe and classify magnetic resonance imaging
      characteristics specific to GMI, and to identify key structure-function
      associations that serve as a basis for rating GMI in clinically relevant ways.
      METHOD: Symmetry, extent of cerebral injury, and pathological pattern for 54
      children (37 males, 17 females) with CP and a predominant GMI pattern on chronic
      phase magnetic resonance imaging were related to gross motor function, motor type
      and topography, epilepsy, intellectual disability, blindness, and deafness.
      RESULTS: Relative to mild GMI where there was no pallidal abnormality, severe
      GMI, comprising pallidal abnormality alone or in conjunction with other deep
      nuclear and generalized cortical-subcortical involvement, was strongly associated
      with Gross Motor Function Classification System levels IV to V (OR 35.7 [95% CI
      3.5, 368.8]). Involvement of the basal ganglia was associated with non
      spastic/mixed motor types, but predominantly where cortical-subcortical grey and
      white matter involvement was not extensive. The prevalence of epilepsy was
      highest where there was diffuse cortical-subcortical involvement and white matter
      loss. INTERPRETATION: Better understanding of structure-function relationships in
      CP and GMI, and how to rate the severity of GMI, will be helpful in the clinical
      context and also as a basis for investigation of causal pathways in CP.

PMID- 25970145
TI  - Cavum Septum Pellucidum in Retired American Pro-Football Players.
AB  - Previous studies report that cavum septum pellucidum (CSP) is frequent among
      athletes with a history of repeated traumatic brain injury (TBI), such as boxers.
      Few studies of CSP in athletes, however, have assessed detailed features of the
      septum pellucidum in a case-control fashion. This is important because prevalence
      of CSP in the general population varies widely (2% to 85%) between studies.
      Further, rates of CSP among American pro-football players have not been described
      previously. We sought to characterize MRI features of the septum pellucidum in a
      series of retired pro-football players with a history of repeated
      concussive/subconcussive head traumas compared with controls. We retrospectively
      assessed retired American pro-football players presenting to our memory clinic
      with cognitive/behavioral symptoms in whom structural MRI was available with
      slice thickness <=2 mm (n=17). Each player was matched to a memory clinic control
      patient with no history of TBI. Scans were interpreted by raters blinded to
      clinical information and TBI/football history, who measured CSP grade (0-absent,
      1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard
      protocol. Sixteen of 17 (94%) players had a CSP graded >=2 compared with 3 of 17
      (18%) controls. CSP was significantly higher grade (p<0.001) and longer in
      players than controls (mean length+/-standard deviation: 10.6 mm+/-5.4 vs. 1.1
      mm+/-1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade
      CSP was more frequent in retired pro-football players compared with patients
      without a history of TBI. 

PMID- 25970146
TI  - An organic khorasan wheat-based replacement diet improves risk profile of
      patients with acute coronary syndrome: a randomized crossover trial.
AB  - Khorasan wheat is an ancient grain with previously reported health benefits in
      clinically healthy subjects. The aim of this study was to examine whether a
      replacement diet, thereby substituting all other cereal grains, with products
      made with organic khorasan wheat could provide additive protective effects in
      reducing lipid, oxidative and inflammatory risk factors, in patients with Acute
      Coronary Syndromes (ACS) in comparison to a similar replacement diet using
      products made from organic modern wheat. A randomized double-blinded crossover
      trial with two intervention phases was conducted on 22 ACS patients (9 F; 13 M).
      The patients were assigned to consume products (bread, pasta, biscuits and
      crackers) made either from organic semi-whole khorasan wheat or organic semi
      whole control wheat for eight weeks in a random order. On average, patients
      ingested 62.0 g dry weight (DW) day-1 khorasan or control semolina; and 140.5 g
      DW day-1 khorasan or control flour, respectively. An eight-week washout period
      was implemented between the respective interventions. Blood analyses were
      performed both at the beginning and end of each intervention phase; thereby
      permitting a comparison of both the khorasan and control intervention phases,
      respectively, on circulatory risk factors for the same patient. Consumption of
      products made with khorasan wheat resulted in a significant amelioration in total
      cholesterol (-6.8%), low-density lipoprotein cholesterol (LDL-C) (-8.1%) glucose
      (-8%) and insulin (-24.6%) from baseline levels, independently of age, sex,
      traditional risk factors, medication and diet quality. Moreover, there was a
      significant reduction in reactive oxygen species (ROS), lipoperoxidation of
      circulating monocytes and lymphocytes, as well as in the levels of Tumor Necrosis
      Factor-alpha. No significant differences from baseline in the same patients were
      observed after the conventional control wheat intervention phase. The present
      results suggest that a replacement diet with cereal products made from organic
      khorasan wheat provides additional protection in patients with ACS. Circulating
      cardiovascular risk factors, including lipid parameters, and markers of both
      oxidative stress and inflammatory status, were reduced, irrespective of the
      number and combination of medicinal therapies with proven efficacy in secondary
      prevention. 

PMID- 25970147
TI  - Comparison of correlates of bone mineral density in individuals adhering to lacto
      ovo, vegan, or omnivore diets: a cross-sectional investigation.
AB  - Vegetarian diets are associated with factors that may not support bone health,
      such as low body mass and low intakes of protein; yet, these diets are alkaline,
      a factor that favors bone mineral density (BMD). This study compared the
      correlates of BMD in young, non-obese adults consuming meat-based (n = 27), lacto
      ovo vegetarian (n = 27), or vegan (n = 28) diets for >=1 year. A 24 h diet
      recall, whole body DXA scan, 24 h urine specimen, and fasting blood sample were
      collected from participants. BMD did not differ significantly between groups.
      Protein intake was reduced ~30% in individuals consuming lacto-ovo and vegan
      diets as compared to those consuming meat-based diets (68 +/- 24, 69 +/- 29, and
      97 +/- 47 g/day respectively, p = 0.006); yet dietary protein was only associated
      with BMD for those following vegan diets. Urinary pH was more alkaline in the
      lacto-ovo and vegan groups versus omnivores (6.5 +/- 0.4, 6.7 +/- 0.4, and 6.2 +/
      0.4 respectively, p = 0.003); yet urinary pH was associated with BMD in
      omnivores only. These data suggest that plant-based diets are not detrimental to
      bone in young adults. Moreover, diet prescriptions for bone health may vary among
      diet groups: increased fruit and vegetable intake for individuals with high meat
      intakes and increased plant protein intake for individuals who follow a
      vegetarian diet plan.

PMID- 25970148
TI  - High prevalence of vitamin D deficiency in pregnant Korean women: the first
      trimester and the winter season as risk factors for vitamin D deficiency.
AB  - We investigated the vitamin D status of Korean women during pregnancy and
      assessed the effects of vitamin D deficiency on two pregnancy outcomes; preterm
      births and the births of small for gestational age. We measured the serum 25
      hydroxyvitamin D levels in 220 pregnant Korean women who were recruited
      prospectively and compared these levels with those of 500 healthy non-pregnant
      women. We analyzed vitamin D status according to patient demographics, season,
      and obstetrical characteristics; moreover, we also assessed pregnancy outcomes.
      The overall prevalence of vitamin D deficiency(<20 ng/mL) in pregnant women and
      healthy non-pregnant women was 77.3% and 79.2%; respectively; and the prevalence
      of severe vitamin D deficiency (<10 ng/mL) was 28.6% and 7.2%; respectively (p <
      0.05). Vitamin D deficiency was more prevalent in the winter (100%) than in the
      summer (45.5%) in pregnant Korean women. A higher risk of vitamin D deficiency
      was observed in the first trimester than in the third trimester (adjusted OR 4.3;
      p < 0.05). No significant association was observed between vitamin D deficiency
      and any of the pregnancy outcomes examined. Further research focusing on the long
      term consequences of vitamin D deficiency during pregnancy in Korean women is
      warranted. 

PMID- 25970150
TI  - Effects of sulfated and non-sulfated beta-glucan extracted from Agaricus
      brasiliensis in breast adenocarcinoma cells - MCF-7.
AB  - The beta-glucans (beta-G) are polysaccharides produced by various organisms, and
      sulfation of beta-G renders them more soluble. With the objective to assess the
      effects of sulfated and non-sulfated beta-G extracted from Agaricus brasiliensis
      in MCF-7 cells, assays were used to evaluate cytotoxicity, genotoxicity, cell
      proliferation and mRNA expression. The sulfated and non-sulfated beta-G showed
      dose-dependent cytotoxicity at concentrations of 5 and 10 MUg/mL, by the MTT
      assay. However, only cytotoxicity was observed after 24 h by the Red Neutral test
      for sulfated beta-G, with no genotoxicity for either beta-G in comet assay.
      Proliferation was decreased only at 72 h at a concentration of 100 MUg/mL of
      sulfated beta-G. Treatment with 5 MUg/mL of sulfated beta-G for 6 h reduced the
      expression of pro-apoptotic genes and stress signaling genes, cell cycle arrest,
      damage and cell migration. The 5 MUg/mL of non-sulfated beta-G for 6 h reduced
      the expression of the stress response gene and signaling damage. These results
      indicate that the cytotoxicity in the MTT is not cell death, and that, in
      general, sulfated beta-G have greater cytotoxicity compared to non-sulfated beta
      G.

PMID- 25970149
TI  - One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast
      without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients.
AB  - There is concern that egg intake may increase blood glucose in patients with type
      2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce
      inflammation in patients at risk for T2DM, including obese subjects and those
      with metabolic syndrome. Thus, we hypothesized that egg intake would not alter
      plasma glucose in T2DM patients when compared to oatmeal intake. Our primary
      endpoints for this clinical intervention were plasma glucose and the inflammatory
      markers tumor necrosis factor (TNF)-alpha and interleukin 6 (IL-6). As secondary
      endpoints, we evaluated additional parameters of glucose metabolism,
      dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35-65
      years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly
      allocated to consume isocaloric breakfasts containing either one egg/day or 40 g
      of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three
      week washout period, subjects were assigned to the alternate breakfast. At the
      end of each period, we measured all primary and secondary endpoints. Subjects
      completed four-day dietary recalls and one exercise questionnaire for each
      breakfast period. There were no significant differences in plasma glucose, our
      primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations,
      insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However,
      after adjusting for gender, age and body mass index, aspartate amino-transferase
      (AST) (p < 0.05) and tumor necrosis factor (TNF)-alpha (p < 0.01), one of our
      primary endpoints were significantly reduced during the egg period. These results
      suggest that compared to an oatmeal-based breakfast, eggs do not have any
      detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast,
      eggs reduce AST and TNF-alpha in this population characterized by chronic low
      grade inflammation. 

PMID- 25970151
TI  - Octopus-inspired multi-arm robotic swimming.
AB  - The outstanding locomotor and manipulation characteristics of the octopus have
      recently inspired the development, by our group, of multi-functional robotic
      swimmers, featuring both manipulation and locomotion capabilities, which could be
      of significant engineering interest in underwater applications. During its little
      studied arm-swimming behavior, as opposed to the better known jetting via the
      siphon, the animal appears to generate considerable propulsive thrust and rapid
      acceleration, predominantly employing movements of its arms. In this work, we
      capture the fundamental characteristics of the corresponding complex pattern of
      arm motion by a sculling profile, involving a fast power stroke and a slow
      recovery stroke. We investigate the propulsive capabilities of a multi-arm
      robotic system under various swimming gaits, namely patterns of arm coordination,
      which achieve the generation of forward, as well as backward, propulsion and
      turning. A lumped-element model of the robotic swimmer, which considers arm
      compliance and the interaction with the aquatic environment, was used to study
      the characteristics of these gaits, the effect of various kinematic parameters on
      propulsion, and the generation of complex trajectories. This investigation
      focuses on relatively high-stiffness arms. Experiments employing a compliant-body
      robotic prototype swimmer with eight compliant arms, all made of polyurethane,
      inside a water tank, successfully demonstrated this novel mode of underwater
      propulsion. Speeds of up to 0.26 body lengths per second (approximately 100 mm s(
      1)), and propulsive forces of up to 3.5 N were achieved, with a non-dimensional
      cost of transport of 1.42 with all eight arms and of 0.9 with only two active
      arms. The experiments confirmed the computational results and verified the multi
      arm maneuverability and simultaneous object grasping capability of such systems. 

PMID- 25970152
TI  - Tris-[8]annulenyl Isocyanurate Trianion Triradical and Hexa-anion from the Alkali
      Metal Reduction of [8]Annulenyl Isocyanate.
AB  - The solution phase alkali metal reduction of [8]annulenyl isocyanate (C8H7NCO)
      yields an EPR spectrum, which reveals electron couplings to seven protons and
      only one nitrogen. Although this strongly suggested that the C8H7NCO anion
      radical was generated, experiments on the oxidized product reveal the actual
      reduced species to be tris-[8]annulenyl isocyanurate. Unlike the previously
      studied phenyl isocyanurate anion radical, the unpaired electron(s) is now
      localized within an [8]annulenyl moiety. Further exposure to metal results in the
      formation of an equilibrium mixture of trianion triradical and trianion radical
      species. The cyclotrimerization to form the isocyanurate is proposed to be driven
      by a reactive C8H7NCO dianion, which is produced from the large equilibrium
      disproportionation of the anion radical. Exhaustive reduction of the tris
      [8]annulenyl isocyanurate with potassium in THF generates the first-ever observed
      hexa-anion of an isocyanurate. NMR analysis reveals that the polarity of the
      carbonyl bonds within this hexa-anion is augmented and is caused by the close
      proximity of K(+) ions, which are tightly ion paired to the three [8]annulenyl
      dianion rings. These preliminary studies on the reduction of C8H7NCO suggest that
      polymeric materials (e.g., polyisocyanates) made from this isocyanate might
      exhibit unique properties. 

PMID- 25970153
TI  - Visceral fat is better related to impaired glucose metabolism than body mass
      index after kidney transplantation.
AB  - The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is
      not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney
      transplantation, performing oral glucose tolerance tests and measuring VAT
      content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal
      glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg,
      impaired glucose tolerance patients 1.3 kg and patients with post-transplant
      diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups).
      Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P <
      0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was
      only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An
      association between BMI and 2-h glucose concentration was lost in adjusted
      models, as opposed to the associations between VAT as percentage of total body
      fat and glucose concentrations (R(2) = 0.132, P < 0.001 and R(2) = 0.097, P =
      0.001, respectively for fasting and 2-h glucose concentration). In conclusion,
      VAT is more closely related to impaired glucose metabolism than BMI after kidney
      transplantation. The association with central obesity should encourage additional
      studies on lifestyle interventions to prevent PTDM.

PMID- 25970155
TI  - The mortality and hospitalization rates associated with the long interdialytic
      gap in thrice-weekly hemodialysis patients.
AB  - Excess mortality and hospitalization have been identified after the 2-day gap in
      thrice-weekly hemodialysis patients compared with 1-day intervals, although
      findings vary internationally. Here we aimed to identify factors associated with
      mortality and hospitalization events in England using an incident cohort of 5864
      hemodialysis patients from years 2002 to 2006 inclusive in the UK Renal Registry
      linked to hospitalization data. Higher admission rates were seen after the 2-day
      gap irrespective of whether thrice-weekly dialysis sequence commenced on a Monday
      or Tuesday (2.4 per year after the 2-day gap vs. 1.4 for the rest of the week,
      rate ratio 1.7). The greatest differences in admission rates were seen in
      patients admitted with fluid overload or with conditions associated with a high
      risk of fluid overload. Increased mortality following the 2-day gap was similarly
      independent of session pattern (20.5 vs. 16.7 per 100 patient years, rate ratio
      1.22), with these increases being driven by out-of-hospital death (rate ratio
      1.59 vs. 1.06 for in-hospital death). Non-white patients had an overall survival
      advantage, with the increased mortality after the 2-day gap being found only in
      whites. Thus, fluid overload may increase the risk of hospital admission after
      the 2-day gap and that the increased out-of-hospital mortality may relate to a
      higher incidence of sudden death. Future work should focus on exploring
      interventions in these subgroups. 

PMID- 25970154
TI  - Rictor/mTORC2 signaling mediates TGFbeta1-induced fibroblast activation and
      kidney fibrosis.
AB  - The mammalian target of rapamycin (mTOR) was recently identified in two
      structurally distinct multiprotein complexes: mTORC1 and mTORC2. Previously, we
      found that Rictor/mTORC2 protects against cisplatin-induced acute kidney injury,
      but the role and mechanisms for Rictor/mTORC2 in TGFbeta1-induced fibroblast
      activation and kidney fibrosis remains unknown. To study this, we initially
      treated NRK-49F cells with TGFbeta1 and found that TGFbeta1 could activate
      Rictor/mTORC2 signaling in cultured cells. Blocking Rictor/mTORC2 signaling with
      Rictor or Akt1 small interfering RNAs markedly inhibited TGFbeta1-induced
      fibronection and alpha-smooth muscle actin expression. Ensuing western blotting
      or immunostaining results showed that Rictor/mTORC2 signaling was activated in
      kidney interstitial myofibroblasts from mice with unilateral ureteral
      obstruction. Next, a mouse model with fibroblast-specific deletion of Rictor was
      generated. These knockout mice were normal at birth and had no obvious kidney
      dysfunction or kidney morphological abnormality within 2 months of birth.
      Compared with control littermates, the kidneys of Rictor knockout mice developed
      less interstitial extracellular matrix deposition and inflammatory cell
      infiltration at 1 or 2 weeks after ureteral obstruction. Thus our study suggests
      that Rictor/mTORC2 signaling activation mediates TGFbeta1-induced fibroblast
      activation and contributes to the development of kidney fibrosis. This may
      provide a therapeutic target for chronic kidney diseases. 

PMID- 25970158
TI  - Smallpox: 12,000 years from plagues to eradication: a dermatologic ailment
      shaping the face of society.

PMID- 25970159
TI  - Absence of N-Methyl-D-Aspartate Receptor IgG Autoantibodies in Schizophrenia: The
      Importance of Cross-Validation Studies.

PMID- 25970160
TI  - Niclosamide suppresses cell migration and invasion in enzalutamide resistant
      prostate cancer cells via Stat3-AR axis inhibition.
AB  - PURPOSE: It is known that over expression of IL6 in prostate cancer cells confer
      enzalutamide resistance and that this may occur through constitutive Stat3
      activation. Additionally, recent pre-clinical studies suggested enzalutamide
      might have the potential adverse effect of inducing metastasis of prostate cancer
      cells via Stat3 activation. This study is aimed to target Stat3 activation and
      improve enzalutamide therapy. EXPERIMENTAL DESIGN: Sensitivity of prostate cancer
      cells to enzalutamide was tested using cell growth assays and clonogenic assays.
      Wound healing and invasion assays were performed to determine cell migration and
      invasion in vitro. Quantitative reverse transcription-PCR, ELISA and Western
      blotting were performed to detect expression levels of PSA, c-Myc, survivin,
      Stat3, and AR. ChIP assay was performed to examine recruitment of AR to the PSA
      promoter. RESULTS: In the present study, we found niclosamide, a previously
      identified novel inhibitor of androgen receptor variant (AR-V7), inhibited Stat3
      phosphorylation, and expression of downstream target genes. Niclosamide
      synergistically reversed enzalutamide resistance in prostate cancer cells and
      combination treatment of niclosamide with enzalutamide significantly induced cell
      apoptosis and inhibited cell growth, colony formation, cell migration and
      invasion. Knock down of Stat3 abrogated enzalutamide resistance resulting in
      reduced recruitment of AR to the PSA promoter in prostate cancer cells expressing
      IL6. Moreover, niclosamide reversed enzalutamide resistance by down-regulating
      Stat3 target gene expression Stat3and abrogating recruitment of AR to PSA
      promoter resulting in PSA inhibition. CONCLUSIONS: This study demonstrated the
      IL6-Stat3-AR axis in prostate cancer is one of the crucial mechanisms of
      enzalutamide resistance. Niclosamide has the potential to target the IL6-Stat3-AR
      pathway to overcome enzalutamide resistance and inhibit migration and invasion in
      advanced prostate cancer.

PMID- 25970161
TI  - VEGF and its receptors in dengue virus infection.
AB  - Vascular permeability determines the severity of dengue virus infection. Vascular
      endothelial growth factor (VEGF) and its (receptor 1) R1 and (receptor 2) R2
      receptors may provide insight about the neurological complications of dengue. We
      report VEGF and its R1 and R2 receptors level in dengue patients and correlate
      these with neurological complications. Consecutive patients with dengue were
      subjected to clinical and neurological evaluations. Their blood counts, serum
      chemistry, including liver and kidney function tests, serum creatine kinase (CK),
      and albumin were measured. VEGF, VEGFR1 and VEGFR2 were measured by ELISA in the
      patients and 16 matched controls. Twenty four patients with dengue were included
      whose ages ranged between 15 and 67 years, and nine of whom were females. Serum
      VEGF level was insignificantly lower in dengue patients whereas VEGFR1 was
      significantly higher (P = 0.01) and VEGFR2 was significantly lower (P = 0.005)
      compared to controls. VEGFR2 correlated with systolic blood pressure,
      coagulopathy, and serum CK levels. None of the other clinical and biochemical
      parameters correlated with VEGF and VEGFR1 levels. VEGFR1 and R2 normalized at 1
      month. VEGFR2 correlates with the clinical severity of dengue and muscle
      dysfunction.

PMID- 25970162
TI  - Generation of highly purified human cardiomyocytes from peripheral blood
      mononuclear cell-derived induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells have an enormous potential for physiological
      studies. A novel protocol was developed combining the derivation of iPS from
      peripheral blood with an optimized directed differentiation to cardiomyocytes and
      a subsequent metabolic selection. The human iPS cells were retrovirally
      dedifferentiated from activated T cells. The subsequent optimized directed
      differentiation protocol yielded 30-45% cardiomyocytes at day 16 of
      differentiation. The derived cardiomyocytes expressed appropriate structural
      markers like cardiac troponin T, alpha-actinin and myosin light chain 2 (MLC2V).
      In a subsequent metabolic selection with lactate, the cardiomyocytes content
      could be increased to more than 90%. Loss of cardiomyocytes during metabolic
      selection were less than 50%, whereas alternative surface antibody-based
      selection procedures resulted in loss of up to 80% of cardiomyocytes.
      Electrophysiological characterization confirmed the typical cardiac features and
      the presence of ventricular, atrial and nodal-like action potentials within the
      derived cardiomyocyte population. Our combined and optimized protocol is highly
      robust and applicable for scalable cardiac differentiation. It provides a simple
      and cost-efficient method without expensive equipment for generating large
      numbers of highly purified, functional cardiomyocytes. It will further enhance
      the applicability of iPS cell-derived cardiomyocytes for disease modeling, drug
      discovery, and regenerative medicine. 

PMID- 25970163
TI  - The Shepherds' Tale: A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci
      in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds.
AB  - Diabetes mellitus is a serious health problem in both dogs and humans. Certain
      dog breeds show high prevalence of the disease, whereas other breeds are at low
      risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of
      glycaemia, where serum concentrations reflect glucose turnover over the past few
      weeks to months. In this study, we searched for genetic factors influencing
      variation in serum fructosamine concentration in healthy dogs using data from
      nine dog breeds. Considering all breeds together, we did not find any genome-wide
      significant associations to fructosamine serum concentration. However, by
      performing breed-specific analyses we revealed an association on chromosome 3
      (pcorrected ~ 1:68 * 10-6) in Belgian shepherd dogs of the Malinois subtype. The
      associated region and its close neighbourhood harbours interesting candidate
      genes such as LETM1 and GAPDH that are important in glucose metabolism and have
      previously been implicated in the aetiology of diabetes mellitus. To further
      explore the genetics of this breed specificity, we screened the genome for
      reduced heterozygosity stretches private to the Belgian shepherd breed. This
      revealed a region with reduced heterozygosity that shows a statistically
      significant interaction (p = 0.025) with the association region on chromosome 3.
      This region also harbours some interesting candidate genes and regulatory regions
      but the exact mechanisms underlying the interaction are still unknown.
      Nevertheless, this finding provides a plausible explanation for breed-specific
      genetic effects for complex traits in dogs. Shepherd breeds are at low risk of
      developing diabetes mellitus. The findings in Belgian shepherds could be
      connected to a protective mechanism against the disease. Further insight into the
      regulation of glucose metabolism could improve diagnostic and therapeutic methods
      for diabetes mellitus. 

PMID- 25970165
TI  - Near Full-Length Identification of a Novel HIV-1 CRF01_AE/B/C Recombinant in
      Northern Myanmar.
AB  - The Myanmar-China border appears to be the "hot spot" region for the occurrence
      of HIV-1 recombination. The majority of the previous analyses of HIV-1
      recombination were based on partial genomic sequences, which obviously cannot
      reflect the reality of the genetic diversity of HIV-1 in this area well. Here, we
      present a near full-length characterization of a novel HIV-1 CRF01_AE/B/C
      recombinant isolated from a long-distance truck driver in Northern Myanmar. It is
      the first description of a near full-length genomic sequence in Myanmar since
      2003, and might be one of the most complicated HIV-1 chimeras ever detected in
      Myanmar, containing four CRF01_AE, six B segments, and five C segments separated
      by 14 breakpoints throughout its genome. The discovery and characterization of
      this new CRF01_AE/B/C recombinant indicate that intersubtype recombination is
      ongoing in Myanmar, continuously generating new forms of HIV-1. More work based
      on near full-length sequence analyses is urgently needed to better understand the
      genetic diversity of HIV-1 in these regions. 

PMID- 25970164
TI  - Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity.
AB  - Increased exposure to blue or visible light, fluctuations in oxygen tension, and
      the excessive accumulation of toxic retinoid byproducts places a tremendous
      amount of stress on the retina. Reduction of visual chromophore biosynthesis may
      be an effective method to reduce the impact of these stressors and preserve
      retinal integrity. A class of non-retinoid, small molecule compounds that target
      key proteins of the visual cycle have been developed. The first candidate in this
      class of compounds, referred to as visual cycle modulators, is emixustat
      hydrochloride (emixustat). Here, we describe the effects of emixustat, an
      inhibitor of the visual cycle isomerase (RPE65), on visual cycle function and
      preservation of retinal integrity in animal models. Emixustat potently inhibited
      isomerase activity in vitro (IC50 = 4.4 nM) and was found to reduce the
      production of visual chromophore (11-cis retinal) in wild-type mice following a
      single oral dose (ED50 = 0.18 mg/kg). Measure of drug effect on the retina by
      electroretinography revealed a dose-dependent slowing of rod photoreceptor
      recovery (ED50 = 0.21 mg/kg) that was consistent with the pattern of visual
      chromophore reduction. In albino mice, emixustat was shown to be effective in
      preventing photoreceptor cell death caused by intense light exposure. Pre
      treatment with a single dose of emixustat (0.3 mg/kg) provided a ~50% protective
      effect against light-induced photoreceptor cell loss, while higher doses (1-3
      mg/kg) were nearly 100% effective. In Abca4-/- mice, an animal model of excessive
      lipofuscin and retinoid toxin (A2E) accumulation, chronic (3 month) emixustat
      treatment markedly reduced lipofuscin autofluorescence and reduced A2E levels by
      ~60% (ED50 = 0.47 mg/kg). Finally, in the retinopathy of prematurity rodent
      model, treatment with emixustat during the period of ischemia and reperfusion
      injury produced a ~30% reduction in retinal neovascularization (ED50 =
      0.46mg/kg). These data demonstrate the ability of emixustat to modulate visual
      cycle activity and reduce pathology associated with various biochemical and
      environmental stressors in animal models. Other attributes of emixustat, such as
      oral bioavailability and target specificity make it an attractive candidate for
      clinical development in the treatment of retinal disease. 

PMID- 25970166
TI  - Automated cytochemistry expanded using novel cellular analysis.

PMID- 25970167
TI  - Parsimonious Model for Simulating Total Mercury and Methylmercury in Boreal
      Streams Based on Riparian Flow Paths and Seasonality.
AB  - The complexity of mercury (Hg) biogeochemistry has made it difficult to model
      surface water concentrations of both total Hg (THg) and especially methylmercury
      (MeHg), the species of Hg having the highest potential for bioaccumulation. To
      simulate THg and MeHg variation in low-order streams, we have adapted a
      conceptual modeling framework where a continuum of lateral flows through riparian
      soils determines streamflow concentrations. The model was applied to seven forest
      catchments located in two boreal regions in Sweden spanning a range of climatic,
      soil, and forest management conditions. Discharge, and simulated riparian soil
      water concentrations profiles, represented by two calibrated parameters, were
      able to explain much of the variability of THg and MeHg concentrations in the
      streams issuing from the catchments (Nash Sutcliffe (NS) up to 0.54 for THg and
      0.58 for MeHg). Model performance for all catchments was improved (NS up to 0.76
      for THg and 0.85 for MeHg) by adding two to four parameters to represent
      seasonality in riparian soil water THg and MeHg concentrations profiles. These
      results are consistent with the hypothesis that riparian flow-pathways and
      seasonality in riparian soil concentrations are the major controls on temporal
      variation of THg and MeHg concentrations in low-order streams. 

PMID- 25970169
TI  - Correction: Demineralized Bone Matrix Combined Bone Marrow Mesenchymal Stem
      Cells, Bone Morphogenetic Protein-2 and Transforming Growth Factor-beta3 Gene
      Promoted Pig Cartilage Defect Repair.

PMID- 25970170
TI  - Effects of Agricultural Management Policies on the Exposure of Black-Winged
      Stilts (Himantopus himantopus) Chicks to Cholinesterase-Inhibiting Pesticides in
      Rice Fields.
AB  - Levels of exposure to pesticides in rice fields can be significant depending on
      the environmental policies practiced. The aim of European Union integrated
      management policy is to reduce pesticide use and impact on environment. Rice
      fields provide an alternative breeding habitat for many waterbirds that are
      exposed to the pesticides used and therefore can be valuable indicators of their
      risk for wildlife. To evaluate integrated management success we examined exposure
      of Black-winged Stilts (Himantopus himantopus) to cholinesterase-inhibiting
      pesticides in rice fields under different types of management by measuring plasma
      cholinesterase activity. Cholinesterase activity was lower in birds sampled in
      (a) 2008 after a period of intense pesticide application, than in (b) 2005-2007
      and 2011 in rice fields subject to integrated management in Donana (SW Spain) and
      (c) in control natural wetlands in Spain and Morocco. During 2009 and 2010,
      cholinesterase activity was lower in rice fields in Donana than in rice fields in
      Larache and Sidi Allal Tazi (NW Morocco). Our results suggest that integrated
      management successfully reduced the exposure of Black-winged Stilts to pesticides
      in most of the years. Care should be taken to implement mosquito and pest crop
      controls on time and with environmentally friendly products in order to reduce
      its impact on wildlife. 

PMID- 25970168
TI  - Nonspecific yet decisive: Ubiquitination can affect the native-state dynamics of
      the modified protein.
AB  - Ubiquitination is one of the most common post-translational modifications of
      proteins, and mediates regulated protein degradation among other cellular
      processes. A fundamental question regarding the mechanism of protein
      ubiquitination is whether and how ubiquitin affects the biophysical nature of the
      modified protein. For some systems, it was shown that the position of ubiquitin
      within the attachment site is quite flexible and ubiquitin does not specifically
      interact with its substrate. Nevertheless, it was revealed that
      polyubiquitination can decrease the thermal stability of the modified protein in
      a site-specific manner because of alterations of the thermodynamic properties of
      the folded and unfolded states. In this study, we used detailed atomistic
      simulations to focus on the molecular effects of ubiquitination on the native
      structure of the modified protein. As a model, we used Ubc7, which is an E2
      enzyme whose in vivo ubiquitination process is well characterized and known to
      lead to degradation. We found that, despite the lack of specific direct
      interactions between the ubiquitin moiety and Ubc7, ubiquitination decreases the
      conformational flexibility of certain regions of the substrate Ubc7 protein,
      which reduces its entropy and thus destabilizes it. The strongest destabilizing
      effect was observed for systems in which Lys48-linked tetra-ubiquitin was
      attached to sites used for in vivo degradation. These results reveal how changes
      in the configurational entropy of the folded state may modulate the stability of
      the protein's native state. Overall, our results imply that ubiquitination can
      modify the biophysical properties of the attached protein in the folded state and
      that, in some proteins, different ubiquitination sites will lead to different
      biophysical outcomes. We propose that this destabilizing effect of polyubiquitin
      on the substrate is linked to the functions carried out by the modification, and
      in particular, regulatory control of protein half-life through proteasomal
      degradation. 

PMID- 25970171
TI  - Top-down mass spectrometry of intact membrane protein complexes reveals
      oligomeric state and sequence information in a single experiment.
AB  - Here we study the intact stoichiometry and top-down fragmentation behavior of
      three integral membrane proteins which were natively reconstituted into detergent
      micelles: the mechano-sensitive ion channel of large conductance (MscL), the
      Kirbac potassium channel and the p7 viroporin from the hepatitis C virus. By
      releasing the proteins under nondenaturing conditions inside the mass
      spectrometer, we obtained their oligomeric sizes. Increasing the ion activation
      (collision energy) causes unfolding and subsequent ejection of a highly charged
      monomer from the membrane protein complexes. Further increase of the ion
      activation then causes collision-induced dissociation (CID) of the ejected
      monomers, with fragments observed which were predominantly found to stem from
      membrane-embedded regions. These experiments show how in a single experiment, we
      can probe the relation between higher-order structure and protein sequence, by
      combining the native MS data with fragmentation obtained from top-down MS. 

PMID- 25970173
TI  - Enhancing the emission intensity and decreasing the full widths at half maximum
      of Ba3Si6O12N2:Eu(2+) by Mg(2+) doping.
AB  - The promising green oxynitride phosphor, Ba3-xMgxSi6O12N2:Eu(2+) was synthesized
      by the solid-state reaction method. The effect of Mg(2+) doping on the structure
      and photoluminescence (PL) properties of Ba3Si6O12N2:Eu(2+) was investigated
      systematically. The results reveal that the phosphor retains the single phase of
      Ba3Si6O12N2, with the lattice expanding upon increasing the Mg(2+) concentration,
      in an appropriate range. This suggests that a large portion of Mg(2+) enters into
      the interstitial sites of the crystal lattice. At a certain concentration, Mg(2+)
      doping can greatly enhance the absorption and PL intensity and decrease the full
      widths at half maximum (FWHM) of Ba3Si6O12N2:Eu(2+) phosphors. The green phosphor
      Ba2.87Eu0.1Mg0.03Si6O12N2 exhibited a small thermal quenching, which remained 82%
      of the initial emission intensity when measured at 150  degrees C. The quantum
      efficiency measured at 400 nm excitation was 38.5%. All the results indicate that
      the solid solution Ba3-xMgxSi6O12N2:Eu(2+) can be a good candidate for phosphors
      applicable in n-UV LEDs for solid-state lighting. 

PMID- 25970172
TI  - Hepatitis B virus replication and sex-determining region Y box 4 production are
      tightly controlled by a novel positive feedback mechanism.
AB  - Hepatitis B virus (HBV) infection is a major cause of liver diseases. However,
      the mechanisms underlying HBV infection and pathogenesis remain largely unknown.
      The sex-determining region Y box 4 (Sox4) is a transcriptional factor, which
      preferentially regulates the development of various organs, tissues, and cancers.
      But, the role of Sox4 in viral infection and pathogenesis has not been
      elucidated. Here, we demonstrated that Sox4 is up-regulated by HBV, and revealed
      the mechanism by which HBV regulates Sox4 expression. First, HBV stimulates Sox4
      expression through transcriptional factor Yin Yang 1 (YY1), which binds to Sox4
      promoter to activate Sox4 transcriptional activity. Second, miR-335, miR-129-2
      and miR-203 inhibit Sox4 expression by targeting its mRNA 3'UTR, while HBV
      suppresses the microRNAs expression, resulting in up-regulating Sox4 post
      transcriptionally. Third, Sox4 protein is degraded by proteasome, while HBV
      surface protein (HBsAg) prevents Sox4 from degradation by directly interacting
      with the protein, thereby enhancing Sox4 production post-translationlly. More
      interestingly, HBV-activated Sox4 in turn facilitates HBV replication by direct
      binding to the viral genome via its HMG box. Thus, this study revealed a novel
      positive feedback mechanism by which Sox4 production and HBV replication are
      tightly correlated. 

PMID- 25970174
TI  - Evolution of viviparity in squamate reptiles: Reversibility reconsidered.
AB  - Viviparity in squamate reptiles is widely recognized as having evolved
      convergently from oviparity more than 100 times. However, questions persist as to
      whether reversals from viviparity back to oviparity have ever occurred. Based on
      a theoretical model, a recent paper (Pyron and Burbrink, 2014) has proposed that
      viviparity is ancestral for squamates and that viviparity-oviparity reversals
      have far outnumbered origins of viviparity in reproductive history. Close
      examination of this analysis reveals features that cast doubt on its
      plausibility, notably the requirement of repeated, sequential transformations
      back and forth between these reproductive modes, as well as numerous, uncounted
      evolutionary transformations that have produced inaccurate estimates of
      parsimony. Evidence derived from studies of anatomy, physiology, and
      developmental biology strongly supports the inference that oviparity is ancestral
      for squamates and has given rise to viviparity on numerous occasions. Biological
      data provide important insights into the likelihood of evolutionary
      transformations, and deserve to be incorporated fully into future analyses of the
      evolution of reproductive modes.

PMID- 25970175
TI  - Intention seekers: conspiracist ideation and biased attributions of
      intentionality.
AB  - Conspiracist beliefs are widespread and potentially hazardous. A growing body of
      research suggests that cognitive biases may play a role in endorsement of
      conspiracy theories. The current research examines the novel hypothesis that
      individuals who are biased towards inferring intentional explanations for
      ambiguous actions are more likely to endorse conspiracy theories, which portray
      events as the exclusive product of intentional agency. Study 1 replicated a
      previously observed relationship between conspiracist ideation and individual
      differences in anthropomorphisation. Studies 2 and 3 report a relationship
      between conspiracism and inferences of intentionality for imagined ambiguous
      events. Additionally, Study 3 again found conspiracist ideation to be predicted
      by individual differences in anthropomorphism. Contrary to expectations, however,
      the relationship was not mediated by the intentionality bias. The findings are
      discussed in terms of a domain-general intentionality bias making conspiracy
      theories appear particularly plausible. Alternative explanations are suggested
      for the association between conspiracism and anthropomorphism. 

PMID- 25970176
TI  - Correction: Whole Genome Comparisons Suggest Random Distribution of Mycobacterium
      ulcerans Genotypes in a Buruli Ulcer Endemic Region of Ghana.

PMID- 25970177
TI  - Correction: the effect of perceived regional accents on individual economic
      behavior: a lab experiment on linguistic performance, cognitive ratings and
      economic decisions.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0113475.]. 

PMID- 25970179
TI  - Correction: Simultaneous Automated Screening and Confirmatory Testing for
      Vasculitis-Specific ANCA.

PMID- 25970178
TI  - Origin, divergence, and phylogeny of asexual Epichloe endophyte in Elymus species
      from western China.
AB  - Asexual Epichloe species are likely derived directly from sexual Epichloe species
      that then lost their capacity for sexual reproduction or lost sexual reproduction
      because of interspecific hybridization between distinct lineages of sexual
      Epichloe and/or asexual Epichloe species. In this study we isolated asexual
      Epichloe endophytes from Elymus species in western China and sequenced intron
      rich regions in the genes encoding beta-tubulin (tubB) and translation elongation
      factor 1-alpha (tefA). Our results showed that there are no gene copies of tubB
      and tefA in any of the isolates. Phylogenetic analysis showed that sequences in
      this study formed a single clade with asexual Epichloe bromicola from Hordeum
      brevisubulatum, which implies asexual Epichloe endophytes that are symbionts in a
      western Chinese Elymus species likely share a common ancestor with asexual E.
      bromicola from European H. brevisubulatum. In addition, our results revealed that
      asexual E. bromicola isolates that are symbionts in a western Chinese Elymus
      species and sexual Epichloe species that are symbionts in a North American Elymus
      species have a different origin. Further analysis found that Epichloe species
      likely originated in Eurasia. In addition, the results support the hypothesis
      that migratory birds or humans might have aided the dispersal of these fungal
      endophytes to other continents. 

PMID- 25970180
TI  - Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial
      Toxicity.
AB  - Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong
      treatment to keep viral titers below detectable levels. The continuous intake of
      antiretroviral drugs however, leads to severe and even life-threatening side
      effects, supposedly by the deleterious impact of nucleoside-analogue type
      compounds on the functioning of the mitochondrial DNA polymerase. For detailed
      investigation of the yet partially understood underlying mechanisms, the
      availability of a versatile model system is crucial. We therefore set out to
      develop the use of Caenorhabditis elegans to study drug induced mitochondrial
      toxicity. Using a combination of molecular-biological and functional assays,
      combined with a quantitative analysis of mitochondrial network morphology, we
      conclude that anti-retroviral drugs with similar working mechanisms can be
      classified into distinct groups based on their effects on mitochondrial
      morphology and biochemistry. Additionally we show that mitochondrial toxicity of
      antiretroviral drugs cannot be exclusively attributed to interference with the
      mitochondrial DNA polymerase. 

PMID- 25970181
TI  - The Day-Hospital of the University Hospital, Bobo Dioulasso: An Example of
      Optimized HIV Management in Southern Burkina Faso.
AB  - OBJECTIVES: To evaluate the epidemiological evolution of patients with HIV
      (PtHIV), between 2002 and 2012, in a day-hospital that became an HIV reference
      centre for south-west Burkina Faso. MATERIALS AND METHODS: This was a
      retrospective study of PtHIV followed in the Bobo Dioulasso university hospital
      since 2002. The study was based on clinical data recorded using ESOPE software
      and analysed using Excel and SAS. RESULTS: A total of 7320 patients have been
      treated at the centre since 2002; the active file of patients increased from 147
      in 2002 to 3684 patients in 2012. Mean age was stable at 38.4 years and the
      majority were female (71%). The delay to initiation of antiretroviral (ARV)
      treatment after HIV diagnosis decreased from 12.9 months in 2002 to 7.2 months in
      2012. The percentage of PtHIV lost to follow-up, untreated for HIV and deaths all
      decreased after 2005. Voluntary anonymous screening and/or an evocative clinical
      picture were the main reasons for HIV diagnosis, usually at a late stage (41.1%
      at WHO stage 3). Virological success increased due to a decrease in time to
      initiation of ARV treatment and an increase in percentage of patients treated
      (90.5% in 2012, mainly with 1st line drugs). However, there was also a slight
      increase in the rate of therapeutic failures and the percentage of patients who
      progressed to 2nd or 3rd line-ARVs. CONCLUSION: Our day-hospital is a good
      example of the implementation of a specialist centre for the management of PtHIV
      in a resource-limited country (Burkina Faso).

PMID- 25970183
TI  - Long recording sequences: how to track the intra-individual variability of
      acoustic signals.
AB  - Recently developed acoustic technologies - like automatic recording units - allow
      the recording of long sequences in natural environments. These devices are used
      for biodiversity survey but they could also help researchers to estimate global
      signal variability at various (individual, population, species) scales. While
      sexually-selected signals are expected to show a low intra-individual variability
      at relatively short time scale, this variability has never been estimated so far.
      Yet, measuring signal variability in controlled conditions should prove useful to
      understand sexual selection processes and should help design acoustic sampling
      schedules and to analyse long call recordings. We here use the overall call
      production of 36 male treefrogs (Hyla arborea) during one night to evaluate
      within-individual variability in call dominant frequency and to test the
      efficiency of different sampling methods at capturing such variability. Our
      results confirm that using low number of calls underestimates call dominant
      frequency variation of about 35% in the tree frog and suggest that the assessment
      of this variability is better by using 2 or 3 short and well-distributed records
      than by using samples made of consecutive calls. Hence, 3 well-distributed 2
      minutes records (beginning, middle and end of the calling period) are sufficient
      to capture on average all the nightly variability, whereas a sample of 10 000
      consecutive calls captures only 86% of it. From a biological point of view, the
      call dominant frequency variability observed in H. arborea (116Hz on average but
      up to 470 Hz of variability during the course of the night for one male)
      challenge about its reliability in mate quality assessment. Automatic acoustic
      recording units will provide long call sequences in the near future and it will
      be then possible to confirm such results on large samples recorded in more
      complex field conditions. 

PMID- 25970182
TI  - Immunosuppressive therapy in patients with aplastic anemia: a single-center
      retrospective study.
AB  - BACKGROUND: Aplastic anemia (AA) is a rare disease in which hematopoietic stem
      cells are severely diminished resulting in hypocellular bone marrow and
      pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing
      radiation, drugs and rare genetic disorders, but in the majority of cases no
      cause can be identified. In the present study we assessed response rate,
      survival, relapse and clonal evolution in patients with AA treated with
      immunosuppressive therapy. METHODS: Patients with AA who received
      immunosuppressive therapy between May 1998 and September 2013 were included in
      this study. Patients with non-severe AA (NSAA) were treated with cyclosporine
      (CsA) and danazol while patients with severe AA (SAA) as well as patients with
      NSAA who progressed to SAA after beginning of the treatment, were candidates for
      receiving antithymocyte globulin in addition to CsA and danazol. RESULTS: Among
      the 63 studied patients, 29 (46%) had NSAA and 34 (54%) had SAA. Three months
      after treatment, overall response was 58.6% in NSAA and 12.9% in patients with
      SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%,
      respectively. Survival rates were significantly higher in patients with NSAA
      compared to patients with SAA as well as in patients who responded at 6 months
      compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse
      occurred in patients who discontinued the therapy more than those who continued
      taking CsA (p value<0.01). The risk of clonal evolution was 9.9% at 10 years and
      22.8% at 15 years after treatment. CONCLUSION: This long-term retrospective study
      indicated that immunosuppressive therapy should be recommended to patients with
      AA. Also, our experience indicated that immunosuppressive therapy should not be
      discontinued after response to therapy in patients with both NSAA and SAA due to
      high risk of relapse. Low dose of CsA should be continued indefinitely.

PMID- 25970184
TI  - Topological data analysis of biological aggregation models.
AB  - We apply tools from topological data analysis to two mathematical models inspired
      by biological aggregations such as bird flocks, fish schools, and insect swarms.
      Our data consists of numerical simulation output from the models of Vicsek and
      D'Orsogna. These models are dynamical systems describing the movement of agents
      who interact via alignment, attraction, and/or repulsion. Each simulation time
      frame is a point cloud in position-velocity space. We analyze the topological
      structure of these point clouds, interpreting the persistent homology by
      calculating the first few Betti numbers. These Betti numbers count connected
      components, topological circles, and trapped volumes present in the data. To
      interpret our results, we introduce a visualization that displays Betti numbers
      over simulation time and topological persistence scale. We compare our
      topological results to order parameters typically used to quantify the global
      behavior of aggregations, such as polarization and angular momentum. The
      topological calculations reveal events and structure not captured by the order
      parameters. 

PMID- 25970185
TI  - When you have lived in a different culture, does returning 'home' not feel like
      home? Predictors of psychological readjustment to the heritage culture.
AB  - Many repatriates find it challenging to readjust to their heritage culture after
      spending a significant period of time abroad. Research on predictors of
      readjustment, however, remains limited. The present study in particular
      investigated the identification of third culture individuals (TCIs) - that is,
      individuals who spent their formative years outside of their heritage culture -
      with an abstract, third culture. Our findings demonstrated that TCIs'
      identification with the third culture was empirically distinct from that of the
      heritage and host cultures. The present study further examined whether several
      variables - sojourner type (TCI vs. non-TCI), perceived conflict between heritage
      and host culture, perceived cultural distance, and cultural identification with
      heritage and other cultures - predicted psychological readjustment (stress,
      anxiety, depression and overall psychological readjustment). The results showed
      that strong heritage culture identification was associated with better
      psychological readjustment, whereas cultural conflict was generally associated
      with poorer readjustment. Furthermore, sojourner type significantly moderated the
      latter association, such that cultural conflict predicted the stress aspect of
      psychological readjustment for non-TCIs, but not for TCIs. As the present
      investigation is the first study to empirically establish identification with a
      'third culture' we discuss implications for the literature on third culture
      individuals and psychological adjustment upon re-entry. 

PMID- 25970186
TI  - Association between Obesity Indices and Insulin Resistance among Healthy Korean
      Adolescents: The JS High School Study.
AB  - OBJECTIVE: To investigate whether indices of obesity are associated with insulin
      resistance in Korean adolescents. METHODS: This study was conducted as a cross
      sectional analysis of 817 healthy adolescents aged 15-16 years without diabetes.
      Percentiles group of weight-for-height, body mass index (BMI)-for-age, waist
      circumference (WC)-for-age, and skin fold thickness (SFT)-for-age were based on
      the 2007 Korean National Growth Charts. Percentiles of waist-to-hip ratio (WHR),
      waist-to-height ratio (WHtR), and percent body fat were calculated for the study
      population. Insulin resistance was estimated by homeostatic model assessment
      (HOMA-IR). Logistic regression models were used to estimate odds ratio for
      insulin resistance according to seven obesity indices. Generalized linear models
      were used to assess the associations between obesity indices and continuous HOMA
      IR levels. RESULTS: Sex and age-adjusted odds ratios (95% confidence interval)
      for insulin resistance, defined as HOMA-IR>2.50, of the 75-94th and >=95th
      percentiles of weight-for-height were 3.87 (2.38-6.30) and 11.37 (5.87-22.02),
      compared to the <50th percentile. Corresponding odds ratios were 3.27 (2.02-5.28)
      and 11.72 (6.05-22.73) for BMI-for-age, 4.72 (2.82-7.88) and 13.22 (6.42-27.23)
      for WC-for-age, 3.67 (2.27-5.94) and 13.58 (6.71-27.48) for WHR, 4.78 (2.99-7.67)
      and 12.84 (6.23-26.46) for WHtR, 2.62 (1.61-4.26) and 6.68 (3.46-12.90) for SFT
      for-age, and 2.29 (1.33-4.26) and 10.06 (4.39-23.06) for body fat. These
      associations were more prominent when insulin resistance was defined as HOMA
      IR>3.16 and were stronger in males than in females. Continuous measure of HOMA-IR
      was significantly associated with body weight, BMI, WC, WHR, WHtR, and SFT in
      both sexes (p<0.001), and with percent body fat in males only (p<0.001).
      CONCLUSION: Our findings suggest that obesity indices are positively associated
      with insulin resistance in apparently healthy adolescents.

PMID- 25970188
TI  - The wingspan of mathematical crystallography.

PMID- 25970187
TI  - On the temperature dependence of H-U(iso) in the riding hydrogen model.
AB  - The temperature dependence of H-U(iso) in N-acetyl-L-4-hydroxyproline monohydrate
      is investigated. Imposing a constant temperature-independent multiplier of 1.2 or
      1.5 for the riding hydrogen model is found to be inaccurate, and severely
      underestimates H-U(iso) below 100 K. Neutron diffraction data at temperatures of
      9, 150, 200 and 250 K provide benchmark results for this study. X-ray diffraction
      data to high resolution, collected at temperatures of 9, 30, 50, 75, 100, 150,
      200 and 250 K (synchrotron and home source), reproduce neutron results only when
      evaluated by aspherical-atom refinement models, since these take into account
      bonding and lone-pair electron density; both invariom and Hirshfeld-atom
      refinement models enable a more precise determination of the magnitude of H-atom
      displacements than independent-atom model refinements. Experimental efforts are
      complemented by computing displacement parameters following the TLS+ONIOM
      approach. A satisfactory agreement between all approaches is found.

PMID- 25970189
TI  - Unification and classification of two-dimensional crystalline patterns using
      orbifolds.
AB  - The concept of an orbifold is particularly suited to classification and
      enumeration of crystalline groups in the euclidean (flat) plane and its elliptic
      and hyperbolic counterparts. Using Conway's orbifold naming scheme, this article
      explicates conventional point, frieze and plane groups, and describes the
      advantages of the orbifold approach, which relies on simple rules for calculating
      the orbifold topology. The article proposes a simple taxonomy of orbifolds into
      seven classes, distinguished by their underlying topological connectedness,
      boundedness and orientability. Simpler 'crystallographic hyperbolic groups' are
      listed, namely groups that result from hyperbolic sponge-like sections through
      three-dimensional euclidean space related to all known genus-three triply
      periodic minimal surfaces (i.e. the P, D, Gyroid, CLP and H surfaces) as well as
      the genus-four I-WP surface. 

PMID- 25970190
TI  - Unveiling the origin of a nonequilibrium dynamic process detected by X-ray photon
      correlation spectroscopy via a finite element analysis approach.
AB  - It is a scientific and engineering challenge to characterize materials under
      nonequilibrium conditions. In recent years, X-ray photon correlation spectroscopy
      (XPCS), a synchrotron-based coherent X-ray scattering technique, has been found
      useful in determining the timescales associated with various nonequilibrium
      processes, with detailed descriptions of the underlying processes lacking. Here,
      both static ultra small angle X-ray scattering (USAXS) and dynamic USAXS-based
      XPCS were used to investigate a transient structural change (a nonequilibrium
      process) associated with an isothermal anneal in a glass polymer composite
      system. While the bulk USAXS technique lacked the required sensitivity to detect
      the change in the microstructures, the local structural reorganization was
      apparent in the XPCS study. The structural changes were modeled using a three
      dimensional finite element analysis approach and wave-propagation theory was used
      to simulate the resulting reciprocal-space coherent scattering intensity.
      Qualitative agreement was found between the modeling and experimental results,
      which validates that stress relaxation in the viscous polymer matrix was
      responsible for the observed changes. This analysis demonstrates that multi
      physics modeling of complex systems can be used to interpret XPCS measurements of
      nonequilibrium processes. 

PMID- 25970191
TI  - The staurolite enigma solved.
AB  - Staurolite has been long considered an enigma because of its remarkable
      pseudosymmetry and the frequent twinning. Staurolite gives two twins whose
      occurrence frequency seems to contradict the condition of lattice restoration
      requested by the reticular theory of twinning, in that the more frequent one
      (Saint Andrews cross twin) has a twin index of 12, whereas the less frequent one
      (Greek cross twin) has a twin index of 6. The hybrid theory of twinning shows
      that the former is actually a hybrid twin with two concurrent sublattices and an
      effective twin index of 6.0. However, this is still not sufficient to explain the
      observed higher occurrence frequency of the Saint Andrews twin. The (pseudo)
      eigensymmetry of the crystallographic orbits of staurolite has been analysed and
      it was found that the whole substructure built on anions is restored (with small
      deviations) by both twin laws, which explains why twinning is frequent in
      staurolite. On the other hand, 45% of the cation sites are quasi-restored in the
      Saint Andrews cross twin, against only 19% for the Greek cross twin: this
      difference finally explains the different occurrence frequencies of the two
      twins. 

PMID- 25970192
TI  - Ambiguity of structure determination from a minimum of diffraction intensities.
AB  - Although the ambiguity of the crystal structures determined directly from
      diffraction intensities has been historically recognized, it is not well
      understood in quantitative terms. Bernstein's theorem has recently been used to
      obtain the number of one-dimensional crystal structures of equal point atoms,
      given a minimum set of diffraction intensities. By a similar approach, the number
      of two- and three-dimensional crystal structures that can be determined from a
      minimum intensity data set is estimated herein. The ambiguity of structure
      determination from the algebraic minimum of data increases at least exponentially
      fast with the increasing structure size. Substituting lower-resolution
      intensities by higher-resolution ones in the minimum data set has little or no
      effect on this ambiguity if the number of such substitutions is relatively small.

PMID- 25970193
TI  - Faces of Platonic solids in all dimensions.
AB  - This paper considers Platonic solids/polytopes in the real Euclidean space R(n)
      of dimension 3 <= n < infinity. The Platonic solids/polytopes are described
      together with their faces of dimensions 0 <= d <= n - 1. Dual pairs of Platonic
      polytopes are considered in parallel. The underlying finite Coxeter groups are
      those of simple Lie algebras of types A(n), B(n), C(n), F4, also called the Weyl
      groups or, equivalently, crystallographic Coxeter groups, and of non
      crystallographic Coxeter groups H3, H4. The method consists of recursively
      decorating the appropriate Coxeter-Dynkin diagram. Each recursion step provides
      the essential information about faces of a specific dimension. If, at each
      recursion step, all of the faces are in the same Coxeter group orbit, i.e. are
      identical, the solid is called Platonic. The main result of the paper is found in
      Theorem 2.1 and Propositions 3.1 and 3.2.

PMID- 25970194
TI  - A multiple-common-lines method to determine the orientation of snapshot
      diffraction patterns from single particles.
AB  - With the development of X-ray free-electron lasers (XFELs), it is possible to
      determine the three-dimensional structures of noncrystalline objects with
      coherent X-ray diffraction imaging. In this diffract-and-destroy mode, many
      snapshot diffraction patterns are obtained from the identical objects which are
      presented one by one in random orientations to the XFEL beam. Determination of
      the orientation of an individual object is essential for reconstruction of a
      three-dimensional structure. Here a new method, called the multiple-common-lines
      method, has been proposed to determine the orientations of high- and low-signal
      snapshot diffraction patterns. The mean errors of recovered orientations (alpha,
      beta, gamma) of high- and low-signal patterns are about 0.14, 0.06, 0.12 and
      0.77, 0.31, 0.60 degrees , respectively; both sets of errors can meet the
      requirements of the reconstruction of a three-dimensional structure.

PMID- 25970195
TI  - Crystallographic data of double antisymmetry space groups.
AB  - This paper presents crystallographic data of double antisymmetry space groups,
      including symmetry-element diagrams, general-position diagrams and positions,
      with multiplicities, site symmetries, coordinates, spin vectors, roto vectors and
      displacement vectors. 

PMID- 25970196
TI  - Changes of physical properties in multiferroic phase transitions.
AB  - The physical property coefficients that arise in a phase transition which are
      zero in the high-symmetry phase and nonzero in the low-symmetry phase are called
      spontaneous coefficients. For all 1601 Aizu species of phase transitions,
      matrices have been constructed which show the nonzero coefficients of a wide
      variety of magnetic and nonmagnetic physical properties including toroidal
      property coefficients in the high-symmetry phase and their corresponding
      spontaneous coefficients in the low-symmetry phase. It is also shown that these
      spontaneous coefficients provide for the distinction of and switching between
      nonferroelastic domain pairs. 

PMID- 25970198
TI  - Effectiveness of Prenatal Screening for Hemoglobinopathies in a Developing
      Country.
AB  - The thalassemias are among the most common monogenic diseases worldwide, a
      national health burden in India. There are estimated 7500-12,000 babies born with
      beta-thalassemia major (beta-TM) every year in this country. Couples who are at
      risk of having children with hemoglobin (Hb) disorders desired to have the option
      of avoiding the birth of an affected child by prenatal diagnosis (PND). Thus, the
      prenatal women are a highly important target group for carrier screening and
      preventing the birth of thalassemic children in the country. The present study
      was conducted among 20,883 pregnant women, irrespective of gravida and duration
      of pregnancy, from the prenatal clinic of Nilratan Sarkar (NRS) Medical College &
      Hospital, Kolkata, West Bengal, India, from February 2009 to November 2012.
      Thalassemia carrier status was assessed by high performance liquid chromatography
      (HPLC) along with red blood cell (RBC) indices. Husbands of all thalassemia
      carrier women were advised and persuaded to undergo screening for
      hemoglobinopathies. The couples were counseled to undergo PND if both of them
      were detected to be thalassemia carriers. The data were statistically analyzed to
      evaluate the efficacy of this procedure. 

PMID- 25970199
TI  - Binding or aggregation? Hazards of interpretation in studies of molecular
      recognition by porphyrins in water.
AB  - Reports have suggested that polar porphyrins such as tetraphenylporphine
      tetrasulfonate (TPPS) can serve as carbohydrate receptors in water. Here we find
      that TPPS shows changes in UV-visible absorption when treated with glucose, but
      that these are best explained by altered aggregation states and not by formation
      of a closely-bound complex. 

PMID- 25970201
TI  - Point Shear Wave Elastography by Acoustic Radiation Force Impulse Quantification
      in Comparison to Transient Elastography for the Noninvasive Assessment of Liver
      Fibrosis in Chronic Hepatitis C: A Prospective International Multicenter Study.
AB  - PURPOSE: The aim of the present prospective European multicenter study was to
      demonstrate the non-inferiority of point shear wave elastography (pSWE) compared
      to transient elastography (TE) for the assessment of liver fibrosis in patients
      with chronic hepatitis C. MATERIALS AND METHODS: 241 patients with chronic
      hepatitis C were prospectively enrolled at 7 European study sites and received
      pSWE, TE and blood tests. Liver biopsy was performed with histological staging by
      a central pathologist. In addition, for inclusion of cirrhotic patients, a
      maximum of 10 % of patients with overt liver cirrhosis confirmed by imaging
      methods were allowed by protocol (n = 24). RESULTS: Owing to slower than expected
      recruitment due to a reduction of liver biopsies, the study was closed after 4
      years before the target enrollment of 433 patients with 235 patients in the
      'intention to diagnose' analysis and 182 patients in the 'per protocol' analysis.
      Therefore, the non-inferiority margin was enhanced to 0.075 but non-inferiority
      of pSWE could not be proven. However, Paired comparison of the diagnostic
      accuracy of pSWE and TE revealed no significant difference between the two
      methods in the 'intention to diagnose' and 'per protocol' analysis (0.81 vs. 0.85
      for F >= 2, p = 0.15; 0.88 vs. 0.92 for F >= 3, p = 0.11; 0.89 vs. 0.94 for F =
      4, p = 0.19). Measurement failure was significantly higher for TE than for pSWE
      (p = 0.030). CONCLUSION: Non-inferiority of pSWE compared to TE could not be
      shown. However, the diagnostic accuracy of pSWE and TE was comparable for the
      noninvasive staging of liver fibrosis in patients with chronic hepatitis C.

PMID- 25970204
TI  - Thermal stability and hcp-fcc allotropic transformation in supported Co metal
      catalysts probed near operando by ferromagnetic NMR.
AB  - Despite the fact that cobalt based catalysts are used at the industrial scale for
      Fischer-Tropsch synthesis, it is not yet clear which cobalt metallic phase is
      actually at work under operando conditions and what is its state of dispersion.
      As it turns out, the different phases of metallic cobalt, fcc and hcp, give rise
      to distinct ferromagnetic nuclear magnetic resonance. Furthermore, within one Co
      metal particle, the occurrence of several ferromagnetic domains of limited sizes
      can be evidenced by the specific resonance of Co in multi-domain particles.
      Consequently, by ferromagnetic NMR, one can follow quantitatively the sintering
      and phase transitions of dispersed Co metal particles in supported catalysts
      under near operando conditions. The minimal size probed by ferromagnetic Co NMR
      is not precisely known but is considered to be in the order of 10 nm for
      supported Co particles at room temperature and increases to about 35 nm at 850 K.
      Here, in Co metal Fischer-Tropsch synthesis catalysts supported on beta-SiC, the
      resonances of the fcc multi-domain, fcc single-domain and hcp Co were clearly
      distinguished. A careful rationalization of their frequency and width dependence
      on temperature allowed a quantitative analysis of the spectra in the temperature
      range of interest, thus reflecting the state of the catalysts under near operando
      conditions that is without the uncertainty associated with prior quenching. The
      allotropic transition temperature was found to start at 600-650 K, which is about
      50 K below the bulk transition temperature. The phase transition was fully
      reversible and a significant part of the hcp phase was found to be stable up to
      850 K. This anomalous behavior that was observed without quenching might prove to
      be crucial to understand and model active species not only in catalysts but also
      in battery materials. 

PMID- 25970202
TI  - Monitoring brain activity with protein voltage and calcium sensors.
AB  - Understanding the roles of different cell types in the behaviors generated by
      neural circuits requires protein indicators that report neural activity with high
      spatio-temporal resolution. Genetically encoded fluorescent protein (FP) voltage
      sensors, which optically report the electrical activity in distinct cell
      populations, are, in principle, ideal candidates. Here we demonstrate that the FP
      voltage sensor ArcLight reports odor-evoked electrical activity in the in vivo
      mammalian olfactory bulb in single trials using both wide-field and 2-photon
      imaging. ArcLight resolved fast odorant-responses in individual glomeruli, and
      distributed odorant responses across a population of glomeruli. Comparisons
      between ArcLight and the protein calcium sensors GCaMP3 and GCaMP6f revealed that
      ArcLight had faster temporal kinetics that more clearly distinguished activity
      elicited by individual odorant inspirations. In contrast, the signals from both
      GCaMPs were a saturating integral of activity that returned relatively slowly to
      the baseline. ArcLight enables optical electrophysiology of mammalian neuronal
      population activity in vivo. 

PMID- 25970206
TI  - Distinct impact of targeted actin cytoskeleton reorganization on mechanical
      properties of normal and malignant cells.
AB  - The actin cytoskeleton is substantially modified in cancer cells because of
      changes in actin-binding protein abundance and functional activity. As a
      consequence, cancer cells have distinctive motility and mechanical properties,
      which are important for many processes, including invasion and metastasis. Here,
      we studied the effects of actin cytoskeleton alterations induced by specific
      nucleation inhibitors (SMIFH2, CK-666), cytochalasin D, Y-27632 and detachment
      from the surface by trypsinization on the mechanical properties of normal Vero
      and prostate cancer cell line DU145. The Young's modulus of Vero cells was 1300+/
      900 Pa, while the prostate cancer cell line DU145 exhibited significantly lower
      Young's moduli (600+/-400 Pa). The Young's moduli exhibited a log-normal
      distribution for both cell lines. Unlike normal cells, cancer cells demonstrated
      diverse viscoelastic behavior and different responses to actin cytoskeleton
      reorganization. They were more resistant to specific formin-dependent nucleation
      inhibition, and reinforced their cortical actin after detachment from the
      substrate. This article is part of a Special Issue entitled: Mechanobiology.

PMID- 25970208
TI  - Three-Dimensional Conductive Nanocomposites Based on Multiwalled Carbon Nanotube
      Networks and PEDOT:PSS as a Flexible Transparent Electrode for Optoelectronics.
AB  - We have synthesized conductive nanocomposites composed of multiwalled carbon
      nanotubes (MWCNTs) and Au nanoparticles (NPs). The Au NPs with an average size of
      approximately 4.3 nm are uniformly anchored on the MWCNT. After being exposed to
      microwave (MW) plasma irradiation, the anchored Au NPs melt and fuse, leading to
      larger aggregates (34 nm) that can connect the MWCNT forming a three-dimensional
      conducting network. The formation of a continuous MWCNT network can produce more
      a conductive pathway, leading to lower sheet resistance. When the Au-MWCNT is
      dispersed in the highly conductive polymer, poly(ethylene
      dioxythiophene):polystyrenesulfonate ( PEDOT: PSS), we can obtain solution
      processable composite formulations for the preparation of a flexible transparent
      electrode. The resulting Au-MWCNT/PEDOT:PSS hybrid films possess a sheet
      resistance of 51 Omega/sq with a transmittance of 86.2% at 550 nm. We also
      fabricate flexible organic solar cells and electrochromic devices to demonstrate
      the potential use of the as-prepared composite electrodes. Compared with the
      indium tin oxide-based devices, both the solar cells and electrochromic devices
      with the composites incorporated as a transparent electrode deliver comparable
      performance.

PMID- 25970210
TI  - Our role, our promise: To protect, promote, and advance the veterinary
      profession.

PMID- 25970207
TI  - Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate
      vaccine correlates with increasing hapten densities on tetanus toxoid, but not on
      CRM197 carriers.
AB  - Vaccines against drugs of abuse have induced antibodies in animals that blocked
      the biological effects of the drug by sequestering the drug in the blood and
      preventing it from crossing the blood-brain barrier. Drugs of abuse are too small
      to induce antibodies and, therefore, require conjugation of drug hapten analogs
      to a carrier protein. The efficacy of these conjugate vaccines depends on several
      factors including hapten design, coupling strategy, hapten density, carrier
      protein selection, and vaccine adjuvant. Previously, we have shown that 1
      (MorHap), a heroin/morphine hapten, conjugated to tetanus toxoid (TT) and mixed
      with liposomes containing monophosphoryl lipid A [L(MPLA)] as adjuvant, partially
      blocked the antinociceptive effects of heroin in mice. Herein, we extended those
      findings, demonstrating greatly improved vaccine induced antinociceptive effects
      up to 3% mean maximal potential effect (%MPE). This was obtained by evaluating
      the effects of vaccine efficacy of hapten 1 vaccine conjugates with varying
      hapten densities using two different commonly used carrier proteins, TT and cross
      reactive material 197 (CRM197). Immunization of mice with these conjugates mixed
      with L(MPLA) induced very high anti-1 IgG peak levels of 400-1500 MUg/mL that
      bound to both heroin and its metabolites, 6-acetylmorphine and morphine. Except
      for the lowest hapten density for each carrier, the antibody titers and affinity
      were independent of hapten density. The TT carrier based vaccines induced long
      lived inhibition of heroin-induced antinociception that correlated with
      increasing hapten density. The best formulation contained TT with the highest
      hapten density of >=30 haptens/TT molecule and induced %MPE of approximately 3%
      after heroin challenge. In contrast, the best formulation using CRM197 was with
      intermediate 1 densities (10-15 haptens/CRM197 molecule), but the %MPE was
      approximately 13%. In addition, the chemical synthesis of 1, the optimization of
      the conjugation method, and the methods for the accurate quantification of hapten
      density are described. 

PMID- 25970212
TI  - Sow housing.

PMID- 25970213
TI  - What is your diagnosis? Cryptorchidism and Sertoli cell tumor.

PMID- 25970214
TI  - What is your diagnosis? Idiopathic calvarial hyperostosis.

PMID- 25970215
TI  - Pathology in practice. Henneguya infection.

PMID- 25970216
TI  - Timely Topics in Nutrition: An overview of fatty acids in companion animal
      medicine.

PMID- 25970217
TI  - Effect of question design on dietary information solicited during veterinarian
      client interactions in companion animal practice in Ontario, Canada.
AB  - OBJECTIVE: To establish the types of initial questions used by veterinarians in
      companion animal practice to solicit nutritional history information from owners
      of dogs and cats, the dietary information elicited, and the relationship between
      initial question-answer sequences and later nutrition-related questions. DESIGN:
      Cross-sectional qualitative conversation analytic study. SAMPLE: 98 appointments
      featuring 15 veterinarians drawn from an observational study of 284 videotaped
      veterinarian-client-patient visits involving 17 veterinarians in companion animal
      practices in eastern Ontario, Canada. PROCEDURES: Veterinarian and client talk
      related to patient nutrition was identified and transcribed; conversation
      analysis was then used to examine the orderly design and details of talk within
      and across turns. Nutrition-related discussions occurred in 172 visits, 98 of
      which contained veterinarian-initiated question-answer sequences about patient
      nutritional history (99 sequences in total, with 2 sequences in 1 visit).
      RESULTS: The predominant question format used by veterinarians was a what
      prefaced question asking about the current content of the patient's diet (75/99).
      Overall, 63 appointments involved a single what-prefaced question in the first
      turn of nutrition talk by the veterinarian (64 sequences in total). Dietary
      information in client responses was typically restricted to the brand name, the
      subtype (eg, kitten), or the brand name and subtype of a single food item. When
      additional diet questions were subsequently posed, they typically sought only
      clarification about the food item previously mentioned by the client. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggested that question design can influence the
      accuracy and completeness of a nutritional history. These findings can
      potentially provide important evidence-based guidance for communication training
      in nutritional assessment techniques.

PMID- 25970218
TI  - Influence of leash side and handlers on pressure mat analysis of gait
      characteristics in small-breed dogs.
AB  - OBJECTIVE: To characterize the gait of small-breed dogs walked on a pressure
      walkway by handlers moving at a metronome-set tempo and to determine the
      influence of handler and leash side on gait characteristics. DESIGN: Prospective
      study. ANIMALS: 5 healthy adult small-breed dogs weighing < 11.4 kg (25 lb).
      PROCEDURES: Dogs were walked by each of 5 handlers moving at a metronome-set
      tempo (100 beats/min). Velocity, cadence, stance time, number of activated
      sensors, total pressure index (TPI), left or right hind reach, and symmetry
      indices were obtained with the leash on the left and right sides of each dog for
      each handler. RESULTS: Coefficients of variation for TPI and stance time
      approximated 30%, whereas coefficients of variation for symmetry indices remained
      < 20%. Changing handlers and leash side did not influence hind limb variables.
      Changing handlers influenced the TPI of the forelimbs, inducing changes of up to
      8%. Leash side accounted for 12% and 14% of the variation in symmetry indices of
      TPI and number of sensors activated between forelimbs, respectively (mean
      alterations for recorded variables, 9%). CONCLUSIONS AND CLINICAL RELEVANCE:
      Symmetry indices appeared to vary less than variables obtained for individual dog
      limbs, and it may therefore be advantageous to determine those indices during
      large trials. Handlers or leash side may be changed in studies focusing on dogs'
      hind limbs without affecting results. Use of symmetry indices is recommended in
      forelimb studies requiring multiple handlers. Pressure walkway analyses of the
      forelimbs should include equal distribution of left- and right-sided leash-led
      trials, given that small-breed dogs tended to shift weight toward the forelimb
      opposite the leash.

PMID- 25970219
TI  - Results of magnetic resonance imaging performed within 48 hours after head trauma
      in dogs and association with outcome: 18 cases (2007-2012).
AB  - OBJECTIVE: To review results of MRI performed within 48 hours after head trauma
      in dogs and identify associations between MRI findings and outcome. DESIGN:
      Retrospective case series. ANIMALS: 18 dogs that underwent MRI within 48 hours
      after known head trauma. PROCEDURES: Medical records were reviewed for
      information on signalment, history, clinical findings, MRI findings, treatment,
      and outcome. RESULTS: 2 dogs were euthanized, 1 died, and 1 had major persistent
      deficits. The remaining 14 dogs had a good outcome, including 9 that recovered
      completely and 5 that had minor persistent deficits. The most common MRI
      abnormalities were intra-axial changes (n = 13) and extra-axial hemorrhage (13).
      Intra-axial changes were best seen on T2-weighted and fluid attenuation inversion
      recovery (FLAIR) images. A mass effect was detected in 9 dogs, 6 of which had a
      midline shift (mean, 2.18 mm). Three dogs had transtentorial herniation, and 2
      had transcranial herniation. Extra-axial hemorrhage was best seen on FLAIR
      images. The most common location was subdural, with subdural extra-axial
      hemorrhage most often seen on the same side as the injury. Epidural hemorrhage
      was seen in 2 dogs. The affected area was larger in these dogs than in dogs with
      subdural hemorrhage. One dog required surgery and the other was euthanized.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with acute (<
      48 hours' duration) head trauma, T2-weighted and FLAIR images provided the most
      diagnostic information. Dogs with injuries affecting the caudal fossa or
      affecting both the rostral and caudal fossae typically had poorer outcomes.

PMID- 25970221
TI  - Retinopathy associated with ivermectin toxicosis in five cats.
AB  - CASE DESCRIPTION: 5 cats from the same household were examined because of a
      sudden onset of tremors, obtundation, blindness, and dilated pupils.
      Approximately 12 hours prior to evaluation, the owner had attempted to treat the
      cats for suspected ear mite (Otodectes cynotis) infestation by aural
      administration of a dose of an ivermectin paste intended for oral administration
      to horses (approx 22 mg/cat; half of the dose was administered into each ear
      canal). CLINICAL FINDINGS: None of the cats had a menace response; all cats had
      dilated pupils and decreased pupillary light reflexes. Findings of fundic
      examination were unremarkable. Electroretinography was performed for 4 cats, and
      b-wave responses were identified as diminished. Toxicological assay results for
      serum samples from 2 cats confirmed the presence of ivermectin (450 and 610
      MUg/L). TREATMENT AND OUTCOME: All 5 cats made a complete recovery. Neurologic
      abnormalities resolved, electroretinographic responses improved, and vision was
      restored with no residual pathological changes detected during fundic
      examination. CLINICAL RELEVANCE: To the authors' knowledge, the information
      reported here provided the first description of ophthalmic and
      electroretinographic findings in cats with ivermectin toxicosis resulting from
      transdermal administration. Clinical signs, including blindness, resolved with
      time, without additional medical intervention.

PMID- 25970220
TI  - Clinical effects of vinorelbine administration in the management of various
      malignant tumor types in dogs: 58 cases (1997-2012).
AB  - OBJECTIVE: To evaluate the effectiveness of vinorelbine in the management of
      various malignant tumor types in dogs. DESIGN: Retrospective case series.
      ANIMALS: 58 dogs with malignant tumors, including pulmonary carcinoma (n = 31),
      histiocytic sarcoma (9), mast cell tumor (5), lymphoma (4), melanoma (2), and 7
      other tumor types (1 each). PROCEDURES: Medical records of dogs treated with
      vinorelbine from December 1997 to December 2012 were reviewed for data regarding
      signalment, clinical signs, physical examination findings, clinicopathologic test
      results, diagnostic imaging results, vinorelbine doses and dose frequency,
      surgery and radiotherapy details when applicable, other chemotherapeutics
      administered, and outcomes. Descriptive, comparative, and survival statistics
      were computed for all dogs and for dogs by histologic subgroup of tumors.
      RESULTS: Vinorelbine was administered palliatively to 44 (76%) dogs. One (2%) dog
      had a complete response for 162 days, 5 (11%) dogs had a partial response for a
      median duration of 91 days, 19 (43%) dogs had stable disease for a median
      duration of 68 days, and 19 (43%) dogs developed progressive disease after a
      median duration of 21 days. Clinical benefit was more difficult to assess in the
      remaining 14 (24%) dogs that received vinorelbine as an adjuvant treatment.
      Overall median time to tumor progression was 103 days (range, 5 to 1,533 days).
      CONCLUSIONS AND CLINICAL RELEVANCE: Vinorelbine appeared to be effective in the
      treatment of several tumor types in dogs. Follow-up prospective studies of the
      clinical benefit of the drug in specific clinical scenarios will be necessary to
      support this conclusion.

PMID- 25970222
TI  - Community rabies knowledge and pet vaccination practices after a skunk rabies
      outbreak in Eddy County, New Mexico.
AB  - OBJECTIVE: To determine percentages of domestic cats and dogs vaccinated against
      rabies, identify barriers to vaccination, and assess knowledge about rabies in a
      semirural New Mexico community after a skunk rabies outbreak. DESIGN: Cross
      sectional, door-to-door, bilingual, community-based participatory survey. SAMPLE:
      366 residential properties in Eddy County, NM. PROCEDURES: The New Mexico
      Department of Health and CDC administered surveys and analyzed data. RESULTS:
      Individuals at 247 of the 366 residential properties participated in the survey.
      One hundred eighty of the 247 (73%) households owned a dog (n = 292) or cat
      (163). Cats were more likely than dogs to not have an up-to-date rabies
      vaccination status (prevalence ratio, 3.2; 95% confidence interval, 2.3 to 4.4).
      Cost and time or scheduling were the most frequently identified barriers to
      vaccination. One hundred sixty (65%) respondents did not know livestock can
      transmit rabies, 78 (32%) did not know rabies is fatal, and 89 (36%) did not know
      a bat scratching a person can be an exposure. Only 187 (76%) respondents
      indicated they would contact animal control if they saw a sick skunk, and only
      166 (67%) indicated they would contact animal control if bitten by a dog they did
      not own. CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that rabies
      vaccination prevalence among pet dogs and cats was low, despite the fact that the
      region had experienced a skunk rabies outbreak during the previous 2 years. In
      addition, substantial percentages of respondents did not have correct knowledge
      of rabies or rabies exposure.

PMID- 25970224
TI  - Bacterial Sliding Clamp Inhibitors that Mimic the Sequential Binding Mechanism of
      Endogenous Linear Motifs.
AB  - The bacterial DNA replication machinery presents new targets for the development
      of antibiotics acting via novel mechanisms. One such target is the protein
      protein interaction between the DNA sliding clamp and the conserved peptide
      linear motifs in DNA polymerases. We previously established that binding of
      linear motifs to the Escherichia coli sliding clamp occurs via a sequential
      mechanism that involves two subsites (I and II). Here, we report the development
      of small-molecule inhibitors that mimic this mechanism. The compounds contain
      tetrahydrocarbazole moieties as "anchors" to occupy subsite I. Functional groups
      appended at the tetrahydrocarbazole nitrogen bind to a channel gated by the side
      chain of M362 and lie at the edge of subsite II. One derivative induced the
      formation of a new binding pocket, termed subsite III, by rearrangement of a loop
      adjacent to subsite I. Discovery of the extended binding area will guide further
      inhibitor development. 

PMID- 25970223
TI  - Genome-wide analysis of small nucleolar RNAs of Leishmania major reveals a rich
      repertoire of RNAs involved in modification and processing of rRNA.
AB  - Trypanosomatids are protozoan parasites and the causative agent of infamous
      infectious diseases. These organisms regulate their gene expression mainly at the
      post-transcriptional level and possess characteristic RNA processing mechanisms.
      In this study, we analyzed the complete repertoire of Leishmania major small
      nucleolar (snoRNA) RNAs by performing RNA-seq analysis on RNAs that were affinity
      purified using the C/D snoRNA core protein, SNU13, and the H/ACA core protein,
      NHP2. This study revealed a large collection of C/D and H/ACA snoRNAs, organized
      in gene clusters generally containing both snoRNA types. Abundant snoRNAs were
      identified and predicted to guide trypanosome-specific rRNA cleavages. The
      repertoire of snoRNAs was compared to that of the closely related Trypanosoma
      brucei, and 80% of both C/D and H/ACA molecules were found to have functional
      homologues. The comparative analyses elucidated how snoRNAs evolved to generate
      molecules with analogous functions in both species. Interestingly, H/ACA RNAs
      have great flexibility in their ability to guide modifications, and several of
      the RNA species can guide more than one modification, compensating for the
      presence of single hairpin H/ACA snoRNA in these organisms. Placing the predicted
      modifications on the rRNA secondary structure revealed hypermodification regions
      mostly in domains which are modified in other eukaryotes, in addition to
      trypanosome-specific modifications. 

PMID- 25970225
TI  - Bioactivation of clopidogrel and prasugrel: factors determining the
      stereochemistry of the thiol metabolite double bond.
AB  - The antithrombotics of the tetrahydrothienopyridine series, clopidogrel and
      prasugrel, are prodrugs that must be metabolized in two steps to become
      pharmacologically active. The first step is the formation of a thiolactone
      metabolite. The second step is a further oxidation with the formation of a
      thiolactone sulfoxide whose hydrolytic opening leads to a sulfenic acid that is
      eventually reduced into the corresponding active cis thiol. Very few data were
      available on the formation of the isomer of the active cis thiol having a trans
      configuration of the double bond, the most striking result in that regard being
      that both cis and trans thiols were formed upon the metabolism of clopidogrel by
      human liver microsomes in the presence of glutathione (GSH), whereas only the cis
      thiol was detected in the sera of patients treated with this drug. This article
      shows that trans thiols are also formed upon the microsomal metabolism of
      prasugrel or its thiolactone metabolite in the presence of GSH and that
      metabolites having the trans configuration of the double bond are only formed
      when microsomal incubations are done in the presence of thiols, such as GSH, N
      acetyl-cysteine, and mercaptoethanol. Intermediate formation of thioesters
      resulting from the reaction of GSH with the thiolactone sulfoxide metabolite
      appears to be responsible for trans thiol formation. Addition of human liver
      cytosol to the microsomal incubations led to a dramatic decrease of the formation
      of the trans thiol metabolites. These data suggest that cytosolic esterases would
      accelerate the hydrolytic opening of thiolactone sulfoxide intermediates and
      disfavor the formation of thioesters resulting from the reaction of these
      intermediates with GSH that is responsible for trans isomer formation. This would
      explain why trans thiols have not been detected in the sera of patients treated
      with clopidogrel.

PMID- 25970226
TI  - A case of mesotherapy-induced panniculitis.
AB  - Mesotherapy was first introduced in Europe for the treatment of localized pain.
      It is currently used mainly for aesthetical purposes and gradually getting widely
      used for body contouring, cellulite reduction, and skin rejuvenation. The reports
      concerning about mesotherapy is increasing in number in the literature. There are
      reported systemic and local side effects of mesotherapy. Panniculitis is a rare
      side effect of mesotherapy. In this article, we report a case of mesotherapy
      induced panniculitis who responded to dapsone therapy. 

PMID- 25970227
TI  - Effect of tetraalkylammonium cations on gas coalescence at a hydrogen-evolving
      microelectrode.
AB  - Hydrogen gas evolution at the surface of a microelectrode may result in periodic
      release of single bubbles larger than the electrode diameter. Bubbles often grow
      by incorporating smaller bubbles that coalesce with them. To explore the
      coalescence, we investigate how a series of six tetralkylammonium cations
      (TXA(+)), where the number of carbons on the alkyl chain varies from 1 to 6,
      affects the oscillatory behavior of the gas-evolving microcathode. Different
      concentrations of TXA(+) bromide salts ranging from a few micromolar up to 1 M
      were added in the acid electrolyte. The frequency of bubble release and the
      transition from periodic to aperiodic release are related to the inhibition of
      bubble coalescence and gas streaming. The concentration range where this
      transition occurs depends strongly on the cation hydrophobicity and it ranges
      from very small values for the hydrophobic cations to over 1 M for the most
      hydrophilic one. For some of the TXA(+) cations, the transition shows a smooth
      increase in release frequency before switching completely to bubble-stream
      behavior, while for others the transition is abrupt. A smooth increase in the gas
      oscillator frequency with concentration indicates that the adsorption of TXA(+)
      cations on the bubble surface is mass transport-limited. The inhibition of bubble
      coalescence by the smallest cations is electrochemically driven, facilitated by
      specific interactions established between the ions and the electrode surface. 

PMID- 25970228
TI  - Overexpression of pyruvate kinase M2 associates with aggressive
      clinicopathological features and unfavorable prognosis in oral squamous cell
      carcinoma.
AB  - Abnormal glucose metabolism mediated by pyruvate kinase M2 (PKM2) fuels cancer
      overgrowth and propagation. However, its expression and oncogenic roles in in
      oral squamous cell carcinoma (OSCC) remains incompletely known. Here, we aimed to
      investigate the expression of PKM2, its prognostic values and oncogenic functions
      using 7,12-dimethyl-1,2-bezan-tracene (DMBA)-induced hamster buccal pouch SCC
      model, primary OSCC specimens as well as in vitro cellular assays. We found that
      in DMBA-induced OSCC model, negative PKM2 expression was commonly observed in
      normal epithelial, while more PKM2 abundance was detected in hyperplasia,
      dysplasia and SCC. Overexpression of PKM2 in a major fraction of OSCC
      significantly associated with tumor size (P = 0.027), cervical node metastasis (P
      = 0.004) and clinical stages (P = 0.000). Patients with increased PKM2 had
      remarkably reduced overall and disease-free survival. Multivariate survival
      analysis further revealed that PKM served as a critical independent prognostic
      factor for patients' overall survival. Furthermore, impaired cell proliferation
      and migration, and reduced apoptosis were detected upon PKM2 knockdown in HN4 and
      HN12 cells. Taken together, our findings reveal that PKM2 is critically involved
      in OSCC initiation and progression probably by promoting cell proliferation and
      migration as well as reducing apoptosis. Its overexpression correlates with
      aggressive clinicopathological features and poor patients' outcome. 

PMID- 25970229
TI  - A comparison of propofol vs. dexmedetomidine for sedation, haemodynamic control
      and satisfaction, during esophagogastroduodenoscopy under conscious sedation.
AB  - WHAT IS KNOWN AND OBJECTIVE: Esophagogastroduodenoscopy (EGD) is a common
      diagnostic procedure which requires sedation for most patients. We undertook a
      prospective, randomized, double-blinded study to compare the effect of propofol
      vs. dexmedetomidine on the sedation of outpatients during EGD. METHODS: Prior to
      the procedure, outpatients received either propofol at 0.6 mg/kg, with additional
      doses of 10-20 mg until the Observer's Assessment of Alertness/Sedation Scale
      (OAA/S) score reached 2-4, or dexmedetomidine at a loading dose of 1 MUg/kg over
      a 10-min period followed by a 0.5 MUg/kg/h infusion until the OAA/S score reached
      2-4. Vital signs, sedation level, adverse events, patients' and endoscopist's
      satisfaction score, and an evaluation of the recovery time were assessed. RESULTS
      AND DISCUSSION: Negligible haemoglobin oxygen saturation (SpO2 ) and respiratory
      rate variations were observed in both groups, although respiratory depression
      occurred in two cases (5.9%) in the propofol group. Mean arterial pressure (MAP)
      in the propofol group decreased during the procedure compared with baseline (P <
      0.05) and was also lower in comparison with the dexmedetomidine group (P < 0.05).
      Heart rate (HR) decreased after the loading dose in the dexmedetomidine group (P
      < 0.05). More patients in the propofol group underwent deeper sedation at the
      beginning of the procedure (P < 0.05), although the recovery time was comparable
      between the two groups (P > 0.05). Three cases (9.1%) in the dexmedetomidine
      group were delayed because of dizziness, bradycardia and nausea. There was a
      higher satisfaction score among patients in the propofol group (P < 0.05),
      although the endoscopist's satisfaction score was comparable between the two
      groups (P > 0.05). WHAT IS NEW AND CONCLUSION: Propofol and dexmedetomidine
      provide a relatively satisfactory level of sedation without clinically notable
      adverse effects during EGD. In addition, patients preferred propofol
      administration for the deeper sedation and rapid recovery, and dexmedetomidine
      exhibited minimal adverse effects on respiratory function.

PMID- 25970231
TI  - Corrigendum.

PMID- 25970230
TI  - Onychomatricoma: epidemiological and clinical findings in a large series of 30
      cases.

PMID- 25970232
TI  - Patients with single ventricle physiology undergoing noncardiac surgery are at
      high risk for adverse events.
AB  - BACKGROUND: Patients with single ventricle physiology are at increased anesthetic
      risk when undergoing noncardiac surgery. OBJECTIVE: To review the outcomes of
      anesthetics for patients with single ventricle physiology undergoing noncardiac
      surgery. METHODS: This study is a retrospective chart review of all patients who
      underwent a palliative procedure for single ventricle physiology between January
      1, 2007 and January 31, 2014. Anesthetic and surgical records were reviewed for
      noncardiac operations that required sedation or general anesthesia. Any
      noncardiac operation occurring prior to completion of a bidirectional Glenn
      procedure was included. Diagnostic procedures, including cardiac catheterization,
      insertion of permanent pacemaker, and procedures performed in the ICU, were
      excluded. RESULTS: During the review period, 417 patients with single ventricle
      physiology had initial palliation. Of these, 70 patients (16.7%) underwent 102
      anesthetics for 121 noncardiac procedures. The noncardiac procedures included
      line insertion (n = 23); minor surgical procedures such as percutaneous
      endoscopic gastrostomy or airway surgery (n = 38); or major surgical procedures
      including intra-abdominal and thoracic operations (n = 41). These interventions
      occurred on median day 60 of life (1-233 days). The procedures occurred most
      commonly in the operating room (n = 79, 77.5%). Patients' median weight was 3.4
      kg (2.4-15 kg) at time of noncardiac intervention. In 102 anesthetics, 26
      patients had an endotracheal tube or tracheostomy in situ, 57 patients underwent
      endotracheal intubation, and 19 patients had a natural or mask airway. An
      intravenous induction was performed in 77 anesthetics, an inhalational induction
      in 17, and a combination technique in 8. The median total anesthetic time was 126
      min (14-594 min). In 22 anesthetics (21.6%), patients were on inotropic support
      upon arrival; an additional 24 patients required inotropic support (23.5%), of
      which dopamine was the most common medication. There were 10 intraoperative
      adverse events (9.8%) including: arrhythmias requiring treatment (n = 4),
      conversion from sedation to a general anesthetic (n = 2), difficult airway (n =
      1), inadvertent extubation with desaturation and bradycardia (n = 1), hypotension
      and desaturation (n = 1), and cardiac arrest (n = 1). Postoperative events (<48
      h) included ST segment changes requiring cardiac catheterization (n = 1), and
      cardiorespiratory arrest (n = 1). Age, size, gender, type of cardiac palliation,
      patient location, procedure location, and type of procedure were not associated
      with adverse outcome. After 62 anesthetics (60.8%), patients went postoperatively
      to the cardiac ICU. There were no deaths at 48 h. CONCLUSION: We observed no
      mortality during or after noncardiac surgery in a high-risk subgroup of palliated
      cardiac patients with single ventricle physiology. However, 11.8% of patients had
      an adverse event associated with their anesthetic.

PMID- 25970234
TI  - Transnational dental care among Canadian immigrants.
AB  - OBJECTIVE: This study examines predictors of transnational dental care
      utilization, or the use of dental care across national borders, over a 4-year
      period among immigrants to Canada. METHODS: Data from the Longitudinal Survey of
      Immigrants to Canada (LSIC, 2001-2005) were used. Sampling and bootstrap weights
      were applied to make the data nationally representative. Bivariate and multiple
      logistic regression analyses were applied to identify factors associated with
      immigrants' transnational dental care utilization. RESULTS: Approximately 13% of
      immigrants received dental care outside Canada over a period of 4 years.
      Immigrants lacking dental insurance (OR = 2.05; 95% CI: 1.55-2.70), those
      reporting dental problems (OR = 1.45; 95% CI: 1.12-1.88), who were female (OR =
      1.59; 95% CI: 1.22-2.08), aged >= 50 years (OR = 2.30; 95% CI: 1.45-3.64), and
      who were always unemployed (OR = 1.70; 95% CI: 1.20-2.39) were more likely to
      report transnational dental care utilization. History of social assistance was
      inversely correlated with the use of dental services outside Canada (OR = 0.48;
      95% CI: 0.30-0.83). CONCLUSIONS: It is estimated that roughly 11 500 immigrants
      have used dental care outside Canada over a 4-year period. Although transnational
      dental care utilization may serve as an individual solution for immigrants'
      initial barriers to accessing dental care, it demonstrates weaknesses to in
      country efforts at providing publicly funded dental care to socially marginalized
      groups. Policy reforms should be enacted to expand dental care coverage among
      adult immigrants.

PMID- 25970233
TI  - Prevalence and Predictors of Poor Recovery from Mild Traumatic Brain Injury.
AB  - Although most patients with mild traumatic brain injury (mTBI) recover within 3
      months, a subgroup of patients experience persistent symptoms. Yet, the
      prevalence and predictors of persistent dysfunction in patients with mTBI remain
      poorly understood. In a longitudinal study, we evaluated predictors of
      symptomatic and cognitive dysfunction in adolescents and young adults with mTBI,
      compared with two control groups-patients with orthopedic injuries and healthy
      uninjured individuals. Outcomes were assessed at 3 months post-injury. Poor
      symptomatic outcome was defined as exhibiting a symptom score higher than 90% of
      the orthopedic control (OC) group, and poor cognitive outcome was defined as
      exhibiting cognitive performance poorer than 90% of the OC group. At 3 months
      post-injury, more than half of the patients with mTBI (52%) exhibited
      persistently elevated symptoms, and more than a third (36.4%) exhibited poor
      cognitive outcome. The rate of high symptom report in mTBI was markedly greater
      than that of typically developing (13%) and OC (17%) groups; the proportion of
      those with poor cognitive performance in the mTBI group exceeded that of
      typically developing controls (15.8%), but was similar to that of the OC group
      (34.9%). Older age at injury, female sex, and acute symptom report were
      predictors of poor symptomatic outcome at 3 months. Socioeconomic status was the
      only significant predictor of poor cognitive outcome at 3 months. 

PMID- 25970235
TI  - Equine atypical myopathy caused by hypoglycin A intoxication associated with
      ingestion of sycamore maple tree seeds.
AB  - REASONS FOR PERFORMING STUDY: Evidence suggest there is a link between equine
      atypical myopathy (EAM) and ingestion of sycamore maple tree seeds. OBJECTIVES:
      To further evaluate the hypothesis that the ingestion of hypoglycin A (HGA)
      containing sycamore maple tree seeds causes acquired multiple acyl-CoA
      dehydrogenase deficiency and might be associated with the clinical and
      pathological signs of EAM. STUDY DESIGN: Case report. METHODS: Necropsy and
      histopathology, using hematoxylin and eosin and Sudan III stains, were performed
      on a 2.5-year-old mare that died following the development of clinical signs of
      progressive muscle stiffness and recumbency. Prior to death, the animal ingested
      sycamore maple tree seeds (Acer pseudoplatanus). Detection of metabolites in
      blood and urine obtained post mortem was performed by rapid ultra-performance
      liquid chromatography-tandem mass spectrometry. Data from this case were compared
      with 3 geldings with no clinical history of myopathy. RESULTS: Macroscopic
      examination revealed fragments of maple tree seeds in the stomach and severe
      myopathy of several muscle groups including Mm. intercostales, deltoidei and
      trapezii. Histologically, the affected muscles showed severe, acute
      rhabdomyolysis with extensive accumulation of finely dispersed fat droplets in
      the cytoplasm of degenerated skeletal muscle cells not present in controls. Urine
      and serum concentrations of several acyl carnitines and acyl glycines were
      increased, and both contained metabolites of HGA, a toxic amino acid present in
      sycamore maple tree seeds. CONCLUSIONS: The study supports the hypothesis that
      ingestion of HGA-containing maple tree seeds may cause EAM due to acquired
      multiple acyl-CoA dehydrogenase deficiency.

PMID- 25970236
TI  - Pathogenicity of members of the vibrionaceae family to cultured juvenile
      sablefish.
AB  - Sablefish Anoplopoma fimbria are a prized seafood species due to their high oil
      content and white flaky flesh. Raising these species in culture can help to
      provide an important source of protein for humans and relief to declining wild
      fish populations. Understanding the environmental factors that influence the
      production of Sablefish is important for successful culturing. The significance
      of host-pathogen interactions in Sablefish culture and the resulting
      environmental implications are unknown. Pathogens could potentially cause losses
      of cultured Sablefish stocks due to disease, while Sablefish cultured in net pens
      may also serve as reservoirs for pathogens and potentially transmit disease to
      wild fish species. In this initial study, the susceptibility of juvenile
      Sablefish to three bacterial pathogens from the family Vibrionaceae was examined.
      Listonella anguillarum, Vibrio ordalii, and V. splendidus can pose serious
      economic threats to cultured fish and shellfish. Groups of juvenile Sablefish
      were exposed to five concentrations of each of the pathogens. Sablefish were
      susceptible to L. anguillarum, but were resistant to V. ordalii and V. splendidus
      at exposure concentrations of <= 1.32 * 107 CFU/mL and <= 3.57 * 106 CFU/mL,
      respectively. The greatest L. anguillarum concentration examined (8.7 * 106
      CFU/mL) resulted in 24% mortality in juvenile Sablefish. A 24% loss of Sablefish
      stock could significantly influence an aquaculture program. As determined by
      multiple logistic regression, the survival of Sablefish to L. anguillarum
      exposure was significantly affected by their body mass, and larger fish had a
      greater probability of survival. Aquaculture operations could employ various
      strategies to minimize the loss of juvenile Sablefish by accounting for their
      size and known susceptibilities to pathogens.

PMID- 25970237
TI  - Implementation of a smoke-free policy in an inpatient psychiatric facility:
      Patient-reported adherence, support, and receipt of nicotine-dependence
      treatment.
AB  - The implementation of smoke-free policies in inpatient psychiatric facilities,
      including patient adherence, mental health nursing staff support, and provision
      of nicotine-dependence treatment to patients, has been reported to be poor. The
      extent to which the quality of smoke-free policy implementation is associated
      with patient views of a policy is unknown. We conducted a cross-sectional survey
      of 181 patients (53.6%, n = 97 smokers; and 46.4%, n = 84 non-smokers) in an
      Australian inpatient psychiatric facility with a total smoke-free policy.
      Smokers' adherence to the policy was poor (83.5% smoked). Only half (53.6%)
      perceived staff to be supportive of the policy. Most smokers used nicotine
      replacement therapy (75.3%); although few received optimal nicotine-dependence
      treatment (19.6%). Overall, 45.9% of patients viewed the smoke-free policy in the
      unit as positive (29.9% smokers; 64.3% non-smokers). For smokers, adhering to the
      ban, perceiving staff to be supportive, and reporting that the nicotine
      replacement therapy reduced cravings to smoke were associated with a more
      positive view towards the smoke-free policy. These findings support the
      importance of patient adherence, mental health nursing staff support, and
      adequate provision of nicotine-dependence treatment in strengthening smoke-free
      policy implementation in inpatient psychiatric settings.

PMID- 25970238
TI  - Learning the inverse kinetics of an octopus-like manipulator in three-dimensional
      space.
AB  - This work addresses the inverse kinematics problem of a bioinspired octopus-like
      manipulator moving in three-dimensional space. The bioinspired manipulator has a
      conical soft structure that confers the ability of twirling around objects as a
      real octopus arm does. Despite the simple design, the soft conical shape
      manipulator driven by cables is described by nonlinear differential equations,
      which are difficult to solve analytically. Since exact solutions of the equations
      are not available, the Jacobian matrix cannot be calculated analytically and the
      classical iterative methods cannot be used. To overcome the intrinsic problems of
      methods based on the Jacobian matrix, this paper proposes a neural network
      learning the inverse kinematics of a soft octopus-like manipulator driven by
      cables. After the learning phase, a feed-forward neural network is able to
      represent the relation between manipulator tip positions and forces applied to
      the cables. Experimental results show that a desired tip position can be achieved
      in a short time, since heavy computations are avoided, with a degree of accuracy
      of 8% relative average error with respect to the total arm length. 

PMID- 25970239
TI  - (Z)-Selective Enol Triflation of alpha-Alkoxyacetoaldehydes: Application to
      Synthesis of (Z)-Allylic Alcohols via Cross-Coupling Reaction and [1,2]-Wittig
      Rearrangement.
AB  - The stereoselective transformation of alpha-alkoxyacetoaldehydes to the
      corresponding (Z)-vinyl triflates was achieved by treatment with phenyl
      triflimide and DBU. The stereochemistry was explained by the "syn-effect," which
      was attributed primarily to an sigma -> pi* interaction. The beta-alkoxy vinyl
      triflates obtained were applied to the stereoselective synthesis of structurally
      diverse (Z)-allylic alcohols via transition metal-catalyzed cross-coupling
      reaction and [1,2]-Wittig rearrangement. 

PMID- 25970240
TI  - Anti-HLA sensitization: should we abandon skin allografts for extensively burned
      patients?

PMID- 25970241
TI  - Cytosolic extensions directly regulate a rhomboid protease by modulating
      substrate gating.
AB  - Intramembrane proteases catalyse the signal-generating step of various cell
      signalling pathways, and continue to be implicated in diseases ranging from
      malaria infection to Parkinsonian neurodegeneration. Despite playing such
      decisive roles, it remains unclear whether or how these membrane-immersed enzymes
      might be regulated directly. To address this limitation, here we focus on
      intramembrane proteases containing domains known to exert regulatory functions in
      other contexts, and characterize a rhomboid protease that harbours calcium
      binding EF-hands. We find calcium potently stimulates proteolysis by endogenous
      rhomboid-4 in Drosophila cells, and, remarkably, when rhomboid-4 is purified and
      reconstituted in liposomes. Interestingly, deleting the amino-terminal EF-hands
      activates proteolysis prematurely, while residues in cytoplasmic loops connecting
      distal transmembrane segments mediate calcium stimulation. Rhomboid regulation is
      not orchestrated by either dimerization or substrate interactions. Instead,
      calcium increases catalytic rate by promoting substrate gating. Substrates with
      cleavage sites outside the membrane can be cleaved but lose the capacity to be
      regulated. These observations indicate substrate gating is not an essential step
      in catalysis, but instead evolved as a mechanism for regulating proteolysis
      inside the membrane. Moreover, these insights provide new approaches for studying
      rhomboid functions by investigating upstream inputs that trigger proteolysis. 

PMID- 25970242
TI  - MYC regulates the core pre-mRNA splicing machinery as an essential step in
      lymphomagenesis.
AB  - Deregulated expression of the MYC transcription factor occurs in most human
      cancers and correlates with high proliferation, reprogrammed cellular metabolism
      and poor prognosis. Overexpressed MYC binds to virtually all active promoters
      within a cell, although with different binding affinities, and modulates the
      expression of distinct subsets of genes. However, the critical effectors of MYC
      in tumorigenesis remain largely unknown. Here we show that during lymphomagenesis
      in Eu-myc transgenic mice, MYC directly upregulates the transcription of the core
      small nuclear ribonucleoprotein particle assembly genes, including Prmt5, an
      arginine methyltransferase that methylates Sm proteins. This coordinated
      regulatory effect is critical for the core biogenesis of small nuclear
      ribonucleoprotein particles, effective pre-messenger-RNA splicing, cell survival
      and proliferation. Our results demonstrate that MYC maintains the splicing
      fidelity of exons with a weak 5' donor site. Additionally, we identify pre
      messenger-RNAs that are particularly sensitive to the perturbation of the MYC
      PRMT5 axis, resulting in either intron retention (for example, Dvl1) or exon
      skipping (for example, Atr, Ep400). Using antisense oligonucleotides, we
      demonstrate the contribution of these splicing defects to the anti
      proliferative/apoptotic phenotype observed in PRMT5-depleted Eu-myc B cells. We
      conclude that, in addition to its well-documented oncogenic functions in
      transcription and translation, MYC also safeguards proper pre-messenger-RNA
      splicing as an essential step in lymphomagenesis. 

PMID- 25970243
TI  - Molecular biology: Splicing does the two-step.

PMID- 25970244
TI  - Genome-wide identification of zero nucleotide recursive splicing in Drosophila.
AB  - Recursive splicing is a process in which large introns are removed in multiple
      steps by re-splicing at ratchet points--5' splice sites recreated after splicing.
      Recursive splicing was first identified in the Drosophila Ultrabithorax (Ubx)
      gene and only three additional Drosophila genes have since been experimentally
      shown to undergo recursive splicing. Here we identify 197 zero nucleotide exon
      ratchet points in 130 introns of 115 Drosophila genes from total RNA sequencing
      data generated from developmental time points, dissected tissues and cultured
      cells. The sequential nature of recursive splicing was confirmed by
      identification of lariat introns generated by splicing to and from the ratchet
      points. We also show that recursive splicing is a constitutive process, that
      depletion of U2AF inhibits recursive splicing, and that the sequence and function
      of ratchet points are evolutionarily conserved in Drosophila. Finally, we
      identify four recursively spliced human genes, one of which is also recursively
      spliced in Drosophila. Together, these results indicate that recursive splicing
      is commonly used in Drosophila, occurs in humans, and provides insight into the
      mechanisms by which some large introns are removed.

PMID- 25970245
TI  - Neurotransmitter and psychostimulant recognition by the dopamine transporter.
AB  - Na(+)/Cl(-)-coupled biogenic amine transporters are the primary targets of
      therapeutic and abused drugs, ranging from antidepressants to the
      psychostimulants cocaine and amphetamines, and to their cognate substrates. Here
      we determine X-ray crystal structures of the Drosophila melanogaster dopamine
      transporter (dDAT) bound to its substrate dopamine, a substrate analogue 3,4
      dichlorophenethylamine, the psychostimulants d-amphetamine and methamphetamine,
      or to cocaine and cocaine analogues. All ligands bind to the central binding
      site, located approximately halfway across the membrane bilayer, in close
      proximity to bound sodium and chloride ions. The central binding site recognizes
      three chemically distinct classes of ligands via conformational changes that
      accommodate varying sizes and shapes, thus illustrating molecular principles that
      distinguish substrates from inhibitors in biogenic amine transporters. 

PMID- 25970246
TI  - Recursive splicing in long vertebrate genes.
AB  - It is generally believed that splicing removes introns as single units from
      precursor messenger RNA transcripts. However, some long Drosophila melanogaster
      introns contain a cryptic site, known as a recursive splice site (RS-site), that
      enables a multi-step process of intron removal termed recursive splicing. The
      extent to which recursive splicing occurs in other species and its mechanistic
      basis have not been examined. Here we identify highly conserved RS-sites in genes
      expressed in the mammalian brain that encode proteins functioning in neuronal
      development. Moreover, the RS-sites are found in some of the longest introns
      across vertebrates. We find that vertebrate recursive splicing requires initial
      definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded
      from the dominant mRNA isoform owing to competition with a reconstituted 5'
      splice site formed at the RS-site after the first splicing step. Conversely, the
      RS-exon is included when preceded by cryptic promoters or exons that fail to
      reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop
      codon such that their inclusion can decrease mRNA stability. Thus, by
      establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms
      emerging from long genes by coupling cryptic elements with inclusion of RS-exons.

PMID- 25970248
TI  - Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity.
AB  - Melanoma treatment is being revolutionized by the development of effective
      immunotherapeutic approaches. These strategies include blockade of immune
      inhibitory receptors on activated T cells; for example, using monoclonal
      antibodies against CTLA-4, PD-1, and PD-L1 (refs 3-5). However, only a subset of
      patients responds to these treatments, and data suggest that therapeutic benefit
      is preferentially achieved in patients with a pre-existing T-cell response
      against their tumour, as evidenced by a baseline CD8(+) T-cell infiltration
      within the tumour microenvironment. Understanding the molecular mechanisms that
      underlie the presence or absence of a spontaneous anti-tumour T-cell response in
      subsets of cases, therefore, should enable the development of therapeutic
      solutions for patients lacking a T-cell infiltrate. Here we identify a melanoma
      cell-intrinsic oncogenic pathway that contributes to a lack of T-cell
      infiltration in melanoma. Molecular analysis of human metastatic melanoma samples
      revealed a correlation between activation of the WNT/beta-catenin signalling
      pathway and absence of a T-cell gene expression signature. Using autochthonous
      mouse melanoma models we identified the mechanism by which tumour-intrinsic
      active beta-catenin signalling results in T-cell exclusion and resistance to anti
      PD-L1/anti-CTLA-4 monoclonal antibody therapy. Specific oncogenic signals,
      therefore, can mediate cancer immune evasion and resistance to immunotherapies,
      pointing to new candidate targets for immune potentiation.

PMID- 25970249
TI  - High-energy physics: Proton smasher spots rare particle decays.

PMID- 25970247
TI  - Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.
AB  - A novel Ebola virus (EBOV) first identified in March 2014 has infected more than
      25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary
      analyses of genome sequences of 81 EBOV collected from March to June 2014 from
      Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent
      transmission event from its natural reservoir followed by sustained human-to
      human infections. It has been reported that the EBOV genome variation might have
      an effect on the efficacy of sequence-based virus detection and candidate
      therapeutics. However, only limited viral information has been available since
      July 2014, when the outbreak entered a rapid growth phase. Here we describe 175
      full-length EBOV genome sequences from five severely stricken districts in Sierra
      Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has
      become more phylogenetically and genetically diverse from July to November 2014,
      characterized by the emergence of multiple novel lineages. The substitution rate
      for the 2014 EBOV was estimated to be 1.23 * 10(-3) substitutions per site per
      year (95% highest posterior density interval, 1.04 * 10(-3) to 1.41 * 10(-3)
      substitutions per site per year), approximating to that observed between previous
      EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants
      extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better
      understand the viral evolution and transmission dynamics of the ongoing outbreak.
      These data will facilitate the international efforts to develop vaccines and
      therapeutics. 

PMID- 25970250
TI  - Mechanical induction of the tumorigenic beta-catenin pathway by tumour growth
      pressure.
AB  - The tumour microenvironment may contribute to tumorigenesis owing to mechanical
      forces such as fibrotic stiffness or mechanical pressure caused by the expansion
      of hyper-proliferative cells. Here we explore the contribution of the mechanical
      pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the
      early stage of mouse colon tumour development in the Notch(+)Apc(+/1638N) mouse
      model, we observed mechanistic pressure stress in the non-tumorous epithelial
      cells caused by hyper-proliferative adjacent crypts overexpressing active Notch,
      which is associated with increased Ret and beta-catenin signalling. We thus
      developed a method that allows the delivery of a defined mechanical pressure in
      vivo, by subcutaneously inserting a magnet close to the mouse colon. The
      implanted magnet generated a magnetic force on ultra-magnetic liposomes,
      stabilized in the mesenchymal cells of the connective tissue surrounding colonic
      crypts after intravenous injection. The magnetically induced pressure
      quantitatively mimicked the endogenous early tumour growth stress in the order of
      1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain
      imaging and shear wave elastography. The exertion of pressure mimicking that of
      tumour growth led to rapid Ret activation and downstream phosphorylation of beta
      catenin on Tyr654, imparing its interaction with the E-cadherin in adherens
      junctions, and which was followed by beta-catenin nuclear translocation after 15
      days. As a consequence, increased expression of beta-catenin-target genes was
      observed at 1 month, together with crypt enlargement accompanying the formation
      of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic
      beta-catenin pathway suggests unexplored modes of tumour propagation based on
      mechanical signalling pathways in healthy epithelial cells surrounding the
      tumour, which may contribute to tumour heterogeneity. 

PMID- 25970252
TI  - D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive
      Compulsive Disorder and Interaction With Antidepressants: A Randomized Clinical
      Trial.
AB  - IMPORTANCE: It is unclear whether d-cycloserine (DCS), a partial N-methyl-d
      aspartate agonist that enhances fear extinction, can augment the effects of
      exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive
      disorder (OCD). OBJECTIVES: To examine whether DCS augments the effects of CBT
      for OCD and to explore (post hoc) whether concomitant antidepressant medication
      moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS: A 12-week,
      double-blind randomized clinical trial with 3-month follow-up conducted at an
      academic medical center between September 4, 2012, and September 26, 2013.
      Participants included 128 adult outpatients with a primary diagnosis of OCD and a
      Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent
      antidepressant medication was permitted if the dose had been stable for at least
      2 months prior to enrollment and remained unchanged during the trial. The main
      analysis was by intention-to-treat population. INTERVENTIONS: All participants
      received a previously validated Internet-based CBT protocol over 12 weeks and
      were randomized to receive either 50 mg of DCS or placebo, administered 1 hour
      before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND
      MEASURES: Clinician-administered Y-BOCS score at week 12 and at 3-month follow
      up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS: In
      the primary intention-to-treat analyses, DCS did not augment the effects of CBT
      compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50]
      at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week
      12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction
      with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005).
      Post hoc analyses revealed that antidepressants significantly impaired treatment
      response in the DCS group but not the placebo group, at both posttreatment and
      follow-up (clinician-rated Y-BOCS: t62 = -3.00; P = .004; and t61 = -3.49; P <
      .001, respectively). In the DCS group, a significantly greater proportion of
      antidepressant-free patients achieved remission status at follow-up (60% [95% CI,
      45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P =
      .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%]
      remission rate in both groups). CONCLUSIONS AND RELEVANCE: The findings suggest
      that antidepressants may interact with DCS to block its facilitating effect on
      fear extinction. Use of DCS may be a promising CBT augmentation strategy but only
      in antidepressant-free patients with OCD. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01649895.

PMID- 25970251
TI  - PPAR-alpha and glucocorticoid receptor synergize to promote erythroid progenitor
      self-renewal.
AB  - Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone
      marrow failure diseases such as Diamond-Blackfan anaemia, are not treatable with
      erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU
      Es) that respond to Epo are either too few in number or are not sensitive enough
      to Epo to maintain sufficient red blood cell production. Treatment of these
      anaemias requires a drug that acts at an earlier stage of red cell formation and
      enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed
      that glucocorticoids specifically stimulate self-renewal of an early erythroid
      progenitor, burst-forming unit erythroid (BFU-E), and increase the production of
      terminally differentiated erythroid cells. Here we show that activation of the
      peroxisome proliferator-activated receptor alpha (PPAR-alpha) by the PPAR-alpha
      agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR)
      to promote BFU-E self-renewal. Over time these agonists greatly increase
      production of mature red blood cells in cultures of both mouse fetal liver BFU-Es
      and mobilized human adult CD34(+) peripheral blood progenitors, with a new and
      effective culture system being used for the human cells that generates normal
      enucleated reticulocytes. Although Ppara(-/-) mice show no haematological
      difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced
      stress erythropoiesis, PPAR-alpha agonists facilitate recovery of wild-type but
      not Ppara(-/-) mice from PHZ-induced acute haemolytic anaemia. We also show that
      PPAR-alpha alleviates anaemia in a mouse model of chronic anaemia. Finally, both
      in control and corticosteroid-treated BFU-E cells, PPAR-alpha co-occupies many
      chromatin sites with GR; when activated by PPAR-alpha agonists, additional PPAR
      alpha is recruited to GR-adjacent sites and presumably facilitates GR-dependent
      BFU-E self-renewal. Our discovery of the role of PPAR-alpha agonists in
      stimulating self-renewal of early erythroid progenitor cells suggests that the
      clinically tested PPAR-alpha agonists we used may improve the efficacy of
      corticosteroids in treating Epo-resistant anaemias. 

PMID- 25970253
TI  - Longitudinal trends of recent HIV-1 infections in Slovenia (1986-2012) determined
      using an incidence algorithm.
AB  - Resolving dilemma whether the rise in the number of HIV diagnoses represents an
      actual increase in HIV transmissions or is a result of improved HIV surveillance
      is crucial before implementing national HIV prevention strategies. Annual
      proportions of recent infections (RI) among newly diagnosed persons infected with
      HIV-1 in Slovenia during 27 years (1986-2012) were determined using an algorithm
      consisting of routine baseline CD4 and HIV viral load measurements and the Aware
      BED EIA HIV-1 Incidence Test (BED test). The study included the highest coverage
      of persons diagnosed with HIV during the entire duration of an HIV epidemic in a
      given country/region (71%). Out of 416 patients, 170 (40.9%) had a baseline CD4
      cell count less than 200 cells/mm(3) and/or HIV-1 viral load less than 400
      copies/ml and were characterized as having a long-standing infection (LSI). The
      remaining 246 patients were additionally tested using the BED test. Overall, 23%
      (97/416) of the patients were labeled RI. The characteristics significantly
      associated with RI were as follows: younger age, acute retroviral syndrome, CDC
      class A and other than C, no AIDS defining illnesses, HIV test performed in the
      past, a higher viral load, and a higher CD4 cell count. An interesting trend in
      the proportion of RI was observed, with a peak in 2005 (47% of RI) and the lowest
      point in 2008 (12%) in parallel with a rise in the numbers of new HIV diagnoses.
      This study could help promote the idea of introducing periodic HIV incidence
      monitoring using a simple and affordable algorithm.

PMID- 25970254
TI  - Autonomous Aerial Refueling Ground Test Demonstration--A Sensor-in-the-Loop, Non
      Tracking Method.
AB  - An essential capability for an unmanned aerial vehicle (UAV) to extend its
      airborne duration without increasing the size of the aircraft is called the
      autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non
      tracking method for probe-and-drogue style autonomous aerial refueling tasks by
      combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision
      based image-processing techniques. The method overcomes the inherit ambiguity
      issues when reconstructing 3D information from traditional 2D images by taking
      advantage of ready to use 3D point cloud data from the camera, followed by well
      established computer vision techniques. These techniques include curve fitting
      algorithms and outlier removal with the random sample consensus (RANSAC)
      algorithm to reliably estimate the drogue center in 3D space, as well as to
      establish the relative position between the probe and the drogue. To demonstrate
      the feasibility of the proposed method on a real system, a ground navigation
      robot was designed and fabricated. Results presented in the paper show that using
      images acquired from a 3D Flash LIDAR camera as real time visual feedback, the
      ground robot is able to track a moving simulated drogue and continuously narrow
      the gap between the robot and the target autonomously. 

PMID- 25970255
TI  - A tapered aluminium microelectrode array for improvement of dielectrophoresis
      based particle manipulation.
AB  - In this work, the dielectrophoretic force (F(DEP)) response of Aluminium
      Microelectrode Arrays with tapered profile is investigated through experimental
      measurements and numerical simulations. A standard CMOS processing technique with
      a step for the formation of a tapered profile resist is implemented in the
      fabrication of Tapered Aluminium Microelectrode Arrays (TAMA). The F(DEP) is
      investigated through analysis of the Clausius-Mossotti factor (CMF) and cross
      over frequency (f(xo)). The performance of TAMA with various side wall angles is
      compared to that of microelectrodes with a straight cut sidewall profile over a
      wide range of frequencies through FEM numerical simulations. Additionally,
      electric field measurement (EFM) is performed through scanning probe microscopy
      (SPM) in order to obtain the region of force focus in both platforms. Results
      showed that the tapered profile microelectrodes with angles between 60 degrees 
      and 70 degrees  produce the highest electric field gradient on the particles.
      Also, the region of the strongest electric field in TAMA is located at the bottom
      and top edge of microelectrode while the strongest electric field in
      microelectrodes with straight cut profile is found at the top corner of the
      microelectrode. The latter property of microelectrodes improves the probability
      of capturing/repelling the particles at the microelectrode's side wall.

PMID- 25970256
TI  - Faults Diagnostics of Railway Axle Bearings Based on IMF's Confidence Index
      Algorithm for Ensemble EMD.
AB  - As train loads and travel speeds have increased over time, railway axle bearings
      have become critical elements which require more efficient non-destructive
      inspection and fault diagnostics methods. This paper presents a novel and
      adaptive procedure based on ensemble empirical mode decomposition (EEMD) and
      Hilbert marginal spectrum for multi-fault diagnostics of axle bearings. EEMD
      overcomes the limitations that often hypothesize about data and computational
      efforts that restrict the application of signal processing techniques. The
      outputs of this adaptive approach are the intrinsic mode functions that are
      treated with the Hilbert transform in order to obtain the Hilbert instantaneous
      frequency spectrum and marginal spectrum. Anyhow, not all the IMFs obtained by
      the decomposition should be considered into Hilbert marginal spectrum. The IMFs'
      confidence index arithmetic proposed in this paper is fully autonomous,
      overcoming the major limit of selection by user with experience, and allows the
      development of on-line tools. The effectiveness of the improvement is proven by
      the successful diagnosis of an axle bearing with a single fault or multiple
      composite faults, e.g., outer ring fault, cage fault and pin roller fault. 

PMID- 25970257
TI  - Effects of Temperature and X-rays on Plastic Scintillating Fiber and Infrared
      Optical Fiber.
AB  - In this study, we have studied the effects of temperature and X-ray energy
      variations on the light output signals from two different fiber-optic sensors, a
      fiber-optic dosimeter (FOD) based on a BCF-12 as a plastic scintillating fiber
      (PSF) and a fiber-optic thermometer (FOT) using a silver halide optical fiber as
      an infrared optical fiber (IR fiber). During X-ray beam irradiation, the
      scintillating light and IR signals were measured simultaneously using a dosimeter
      probe of the FOD and a thermometer probe of the FOT. The probes were placed in a
      beaker with water on the center of a hotplate, under variation of the tube
      potential of a digital radiography system or the temperature of the water in the
      beaker. From the experimental results, in the case of the PSF, the scintillator
      light output at the given tube potential decreased as the temperature increased
      in the temperature range from 25 to 60  degrees C. We demonstrated that commonly
      used BCF-12 has a significant temperature dependence of -0.263 +/- 0.028%/
      degrees C in the clinical temperature range. Next, in the case of the IR fiber,
      the intensity of the IR signal was almost uniform at each temperature regardless
      of the tube potential range from 50 to 150 kVp. Therefore, we also demonstrated
      that the X-ray beam with an energy range used in diagnostic radiology does not
      affect the IR signals transmitted via a silver halide optical fiber. 

PMID- 25970258
TI  - Current Sensor Fault Diagnosis Based on a Sliding Mode Observer for PMSM Driven
      Systems.
AB  - This paper proposes a current sensor fault detection method based on a sliding
      mode observer for the torque closed-loop control system of interior permanent
      magnet synchronous motors. First, a sliding mode observer based on the extended
      flux linkage is built to simplify the motor model, which effectively eliminates
      the phenomenon of salient poles and the dependence on the direct axis inductance
      parameter, and can also be used for real-time calculation of feedback torque.
      Then a sliding mode current observer is constructed in alphabeta coordinates to
      generate the fault residuals of the phase current sensors. The method can
      accurately identify abrupt gain faults and slow-variation offset faults in real
      time in faulty sensors, and the generated residuals of the designed fault
      detection system are not affected by the unknown input, the structure of the
      observer, and the theoretical derivation and the stability proof process are
      concise and simple. The RT-LAB real-time simulation is used to build a simulation
      model of the hardware in the loop. The simulation and experimental results
      demonstrate the feasibility and effectiveness of the proposed method. 

PMID- 25970259
TI  - Fusing range measurements from ultrasonic beacons and a laser range finder for
      localization of a mobile robot.
AB  - This paper proposes a method for mobile robot localization in a partially unknown
      indoor environment. The method fuses two types of range measurements: the range
      from the robot to the beacons measured by ultrasonic sensors and the range from
      the robot to the walls surrounding the robot measured by a laser range finder
      (LRF). For the fusion, the unscented Kalman filter (UKF) is utilized. Because
      finding the Jacobian matrix is not feasible for range measurement using an LRF,
      UKF has an advantage in this situation over the extended KF. The locations of the
      beacons and range data from the beacons are available, whereas the correspondence
      of the range data to the beacon is not given. Therefore, the proposed method also
      deals with the problem of data association to determine which beacon corresponds
      to the given range data. The proposed approach is evaluated using different sets
      of design parameter values and is compared with the method that uses only an LRF
      or ultrasonic beacons. Comparative analysis shows that even though ultrasonic
      beacons are sparsely populated, have a large error and have a slow update rate,
      they improve the localization performance when fused with the LRF measurement. In
      addition, proper adjustment of the UKF design parameters is crucial for full
      utilization of the UKF approach for sensor fusion. This study contributes to the
      derivation of a UKF-based design methodology to fuse two exteroceptive
      measurements that are complementary to each other in localization. 

PMID- 25970260
TI  - Prevalence of HIV-1 Subtypes and Drug Resistance-Associated Mutations in HIV-1
      Positive Treatment-Naive Pregnant Women in Pointe Noire, Republic of the Congo
      (Kento-Mwana Project).
AB  - The Kento-Mwana project was carried out in Pointe Noire, Republic of the Congo,
      to prevent mother-to-child HIV-1 transmission. To determine the prevalence of
      different subtypes and transmitted drug resistance-associated mutations, 95
      plasma samples were collected at baseline from HIV-1-positive naive pregnant
      women enrolled in the project during the years 2005-2008. Full protease and
      partial reverse transcriptase sequencing was performed and 68/95 (71.6%) samples
      were successfully sequenced. Major mutations to nucleoside reverse transcriptase
      inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease
      inhibitors were detected in 4/68 (5.9%), 3/68 (4.4%), and 2/68 (2.9%) samples,
      respectively. Phylogenetic analysis of HIV-1 isolates showed a high prevalence of
      unique recombinant forms (24/68, 35%), followed by CRF45_cpx (7/68, 10.3%) and
      subsubtype A3 and subtype G (6/68 each, 8.8%). Although the prevalence of
      transmitted drug resistance mutations appears to be currently limited, baseline
      HIV-1 genotyping is highly advisable in conjunction with antiretroviral therapy
      scale-up in resource-limited settings to optimize treatment and prevent perinatal
      transmission. 

PMID- 25970261
TI  - Evidence of 1,4-dioxane attenuation at groundwater sites contaminated with
      chlorinated solvents and 1,4-dioxane.
AB  - There is a critical need to develop appropriate management strategies for 1,4
      dioxane (dioxane) due to its widespread occurrence and perceived recalcitrance at
      groundwater sites where chlorinated solvents are present. A comprehensive
      evaluation of California state (GeoTracker) and Air Force monitoring records was
      used to provide significant evidence of dioxane attenuation at field sites.
      Temporal changes in the site-wide maximum concentrations were used to estimate
      source attenuation rates at the GeoTracker sites (median length of monitoring
      period = 6.8 years). While attenuation could not be established at all sites,
      statistically significant positive attenuation rates were confirmed at 22 sites.
      At sites where dioxane and chlorinated solvents were present, the median value of
      all statistically significant dioxane source attenuation rates (equivalent half
      life = 31 months; n = 34) was lower than 1,1,1-trichloroethane (TCA) but similar
      to 1,1-dichloroethene (1,1-DCE) and trichloroethene (TCE). Dioxane attenuation
      rates were positively correlated with rates for 1,1-DCE and TCE but not TCA. At
      this set of sites, there was little evidence that chlorinated solvent remedial
      efforts (e.g., chemical oxidation, enhanced bioremediation) impacted dioxane
      attenuation. Attenuation rates based on well-specific records from the Air Force
      data set confirmed significant dioxane attenuation (131 out of 441 wells) at a
      similar frequency and extent (median equivalent half-life = 48 months) as
      observed at the California sites. Linear discriminant analysis established a
      positive correlation between dioxane attenuation and increasing concentrations of
      dissolved oxygen, while the same analysis found a negative correlation with
      metals and CVOC concentrations. The magnitude and prevalence of dioxane
      attenuation documented here suggest that natural attenuation may be used to
      manage some but not necessarily all dioxane-impacted sites. 

PMID- 25970262
TI  - ChSeq: A database of chameleon sequences.
AB  - Chameleon sequences (ChSeqs) refer to sequence strings of identical amino acids
      that can adopt different conformations in protein structures. Researchers have
      detected and studied ChSeqs to understand the interplay between local and global
      interactions in protein structure formation. The different secondary structures
      adopted by one ChSeq challenge sequence-based secondary structure predictors.
      With increasing numbers of available Protein Data Bank structures, we here
      identify a large set of ChSeqs ranging from 6 to 10 residues in length. The
      homologous ChSeqs discovered highlight the structural plasticity involved in
      biological function. When compared with previous studies, the set of unrelated
      ChSeqs found represents an about 20-fold increase in the number of detected
      sequences, as well as an increase in the longest ChSeq length from 8 to 10
      residues. We applied secondary structure predictors on our ChSeqs and found that
      methods based on a sequence profile outperformed methods based on a single
      sequence. For the unrelated ChSeqs, the evolutionary information provided by the
      sequence profile typically allows successful prediction of the prevailing
      secondary structure adopted in each protein family. Our dataset will facilitate
      future studies of ChSeqs, as well as interpretations of the interplay between
      local and nonlocal interactions. A user-friendly web interface for this ChSeq
      database is available at prodata.swmed.edu/chseq. 

PMID- 25970263
TI  - Male sexual behaviour and ethanol consumption from an evolutionary perspective: A
      comment on "Sexual Deprivation Increases Ethanol Intake in Drosophila".
AB  - Shohat-Ophir et al. (1) demonstrate a connection between sexual behaviour and
      ethanol consumption in male Drosophila flies, and how the neuropeptide F system
      regulates ethanol preference. Their results are rightly discussed only in a
      physiological context, but this has facilitated erroneous anthropomorphic
      interpretations by the media. Here we discuss the link between male sexual
      behaviour and ethanol consumption from an evolutionary perspective, providing a
      broader context to interpret their results. 

PMID- 25970264
TI  - Limited Sexual Reproduction and Quick Turnover in the Population Genetic
      Structure of Phytophthora infestans in Fujian, China.
AB  - The mating system plays an important role in the spatiotemporal dynamics of
      pathogen populations through both its direct and indirect impact on the
      generation and distribution of genetic variation. Here, we used a combination of
      microsatellite and phenotypic markers to investigate the spatiotemporal
      distribution of genetic variation in Phytophthora infestans isolates collected
      from Fujian, China and to determine the role of sexual reproduction in the
      dynamics. Although the pathogen populations in this region were dominated by self
      fertile genotypes, sexual reproduction only occurred occasionally and its
      contributions to the population genetic structure of P. infestans and epidemics
      of late blight in the region were limited. Only 49 genotypes were detected among
      the 534 isolates assayed and the pathogen populations displayed significant
      heterozygosity excess. Hierarchical analysis revealed that 21.42% of genetic
      variation was attributed to the difference among sampling years while only 4.45%
      was attributed to the difference among locations, suggesting temporal factors
      play a more important role in the population genetic dynamics of P. infestans
      than spatial factors in this region. We propose that clonal reproduction,
      combined with founder effects and long distance dispersal of sporangia, is
      responsible for the observed pattern of spatiotemporal dynamics in P. infestans. 

PMID- 25970266
TI  - Production of Bio-Energy from Pig Manure: A Focus on the Dynamics Change of Four
      Parameters under Sunlight-Dark Conditions.
AB  - This study investigated the effect of sunlight-dark conditions on volatile fatty
      acids (VFAs), total ammonium nitrogen (TAN), total alkalinity (TA) and pH during
      pig manure (PM) digestion and then the subsequent influence on biogas yield of
      PM. PM1 and PM2 were performed in a transparent reactor and a non-transparent
      reactor, respectively. Two sets of experiments were conducted with a temperature
      of 35.0+/-2.0  degrees C and a total solid concentration of 8.0% to the digestion
      material. The dynamic change of the four parameters in response to sunlight-dark
      conditions resulted in variations of the physiological properties in the digester
      and affected the cumulative biogas production (CBP). PM1 obtained higher CBP
      (15020.0 mL) with a more stable pH and a lower TAN concentration (1414.5 mg/L)
      compared to PM2 (2675.0 mL and 1670.0 mg/L, respectively). The direct path
      coefficients and indirect path coefficients between the four parameters and CBP
      were also analyzed. 

PMID- 25970265
TI  - Structures of potent anticancer compounds bound to tubulin.
AB  - Small molecules that bind to tubulin exert powerful effects on cell division and
      apoptosis (programmed cell death). Cell-based high-throughput screening combined
      with chemo/bioinformatic and biochemical analyses recently revealed a novel
      compound MI-181 as a potent mitotic inhibitor with heightened activity towards
      melanomas. MI-181 causes tubulin depolymerization, activates the spindle assembly
      checkpoint arresting cells in mitosis, and induces apoptotic cell death. C2 is an
      unrelated compound previously shown to have lethal effects on microtubules in
      tumorigenic cell lines. We report 2.60 A and 3.75 A resolution structures of MI
      181 and C2, respectively, bound to a ternary complex of alphabeta-tubulin, the
      tubulin-binding protein stathmin, and tubulin tyrosine ligase. In the first of
      these structures, our crystallographic results reveal a unique binding mode for
      MI-181 extending unusually deep into the well-studied colchicine-binding site on
      beta-tubulin. In the second structure the C2 compound occupies the colchicine
      binding site on beta-tubulin with two chemical moieties recapitulating contacts
      made by colchicine, in combination with another system of atomic contacts. These
      insights reveal the source of the observed effects of MI-181 and C2 on
      microtubules, mitosis, and cultured cancer cell lines. The structural details of
      the interaction between tubulin and the described compounds may guide the
      development of improved derivative compounds as therapeutic candidates or
      molecular probes to study cancer cell division. 

PMID- 25970267
TI  - Synthesis and characterization of M(II) (M = Mn, Fe and Co) azafulvene complexes
      and their X3(-) derivatives.
AB  - The syntheses of M(ii) (M = Mn, Fe, Co) complexes bearing the tris(5
      cycloaminoazafulvene-2-methyl)amine (H3N(afa(Cy))3) ligand in its datively
      coordinated, tautomeric form is reported. The metal-azafulvene complexes
      [N(afa(Cy))3M](OTf)2 are generated in high yields, featuring a secondary
      coordination sphere composed of amino moieties from the ligand platform. To
      investigate the ability of the hydrogen bonding network to support hydrogen-bond
      accepting, coordinating anions, pseudohalide derivatives, [N(afa(Cy))3MX](OTf) (X
      = NCS(-), NCO(-), N3(-)) were synthesized by exposure of [N(afa(Cy))3M](OTf)2 to
      an equivalent of the corresponding salt, [((n)Bu)4N](X). Structural
      characterization of the products reveals two isomorphs of the desired species.
      One complex features a single hydrogen bonding interaction with the pseudohalide,
      while the second compound has two H-bonds from the secondary coordination sphere
      to the coordinated anion. These complexes showcase the structural and electron
      flexibility of the ligand platform, presenting a scaffold capable of accessing a
      different number of hydrogen bonds for stabilizing a given moiety. 

PMID- 25970268
TI  - Salivary gland development and disease.
AB  - Mammalian salivary glands synthesize and secrete saliva via a vast interconnected
      network of epithelial tubes attached to secretory end units. The extensive
      morphogenesis required to establish this organ is dependent on interactions
      between multiple cell types (epithelial, mesenchymal, endothelial, and neuronal)
      and the engagement of a wide range of signaling pathways. Here we describe
      critical regulators of salivary gland development and discuss how mutations in
      these impact human organogenesis. In particular, we explore the genetic
      contribution of growth factor pathways, nerve-derived factors and extracellular
      matrix molecules to salivary gland formation in mice and humans.

PMID- 25970271
TI  - Correction: A Novel GJA8 Mutation (p.V44A) Causing Autosomal Dominant Congenital
      Cataract.

PMID- 25970269
TI  - Pleistocene aridification cycles shaped the contemporary genetic architecture of
      Southern African baboons.
AB  - Plio-Pleistocene environmental change influenced the evolutionary history of many
      animal lineages in Africa, highlighting key roles for both climate and tectonics
      in the evolution of Africa's faunal diversity. Here, we explore diversification
      in the southern African chacma baboon Papio ursinus sensu lato and reveal a
      dominant role for increasingly arid landscapes during past glacial cycles in
      shaping contemporary genetic structure. Recent work on baboons (Papio spp.)
      supports complex lineage structuring with a dominant pulse of diversification
      occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely
      untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data
      supports a scenario where chacma baboon populations were likely restricted to
      refugia during periods of regional cooling and drying through the Late
      Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are
      strongly geographically structured, and demographic reconstruction together with
      spatial analysis of genetic variation point to possible climate-driven isolating
      events where baboons may have retreated to more optimum conditions during cooler,
      drier periods. Our analysis highlights a period of continuous population growth
      beginning in the Middle to Late Pleistocene in both the ursinus and the PG2
      griseipes lineages. All three clades identified in the study then enter a state
      of declining population size (Nef) through to the Holocene; this is particularly
      marked in the last 20,000 years, most likely coincident with the Last Glacial
      Maximum. The pattern recovered here conforms to expectations based on the dynamic
      regional climate trends in southern Africa through the Pleistocene and provides
      further support for complex patterns of diversification in the region's
      biodiversity. 

PMID- 25970270
TI  - Natural populations of shipworm larvae are attracted to wood by waterborne
      chemical cues.
AB  - The life cycle of many sessile marine invertebrates includes a dispersive
      planktonic larval stage whose ability to find a suitable habitat in which to
      settle and transform into benthic adults is crucial to maximize fitness. To
      facilitate this process, invertebrate larvae commonly respond to habitat-related
      chemical cues to guide the search for an appropriate environment. Furthermore,
      small-scale hydrodynamic conditions affect dispersal of chemical cues, as well as
      swimming behavior of invertebrate larvae and encounter with potential habitats.
      Shipworms within the family Teredinidae are dependent on terrestrially derived
      wood in order to complete their life cycle, but very little is known about the
      cues and processes that promote settlement. We investigated the potential for
      remote detection of settling substrate via waterborne chemical cues in teredinid
      larvae through a combination of empirical field and laboratory flume experiments.
      Natural populations of teredinid larvae were significantly more abundant close to
      wooden structures enclosed in plankton net compared to empty control nets,
      clearly showing that shipworm larvae can sense and respond to chemical cues
      associated with suitable settling substrate in the field. However, the flume
      experiments, using ecologically relevant flow velocities, showed that the
      boundary layer around experimental wooden panels was thin and that the mean flow
      velocity exceeded larval swimming velocity approximately 5 mm (~ 25 larval body
      lengths) from the panel surface. Therefore, we conclude that the scope for remote
      detection of waterborne cues is limited and that the likely explanation for the
      higher abundance of shipworm larvae associated with the wooden panels in the
      field is a response to a cue during or after attachment on, or very near, the
      substrate. Waterborne cues probably guide the larva in its decision to remain
      attached and settle, or to detach and continue swimming and drifting until the
      next encounter with a solid substrate. 

PMID- 25970272
TI  - Beat-to-beat heart rate and blood pressure variability and hypertensive disease
      in pregnancy.
AB  - OBJECTIVE: The aim of this study is to determine the relationship between heart
      rate and/or blood pressure variability, measured at 28 weeks' gestation, and the
      incidence of pregnancy-induced hypertension or preeclampsia. STUDY DESIGN:
      Secondary analysis of data from a prospectively enrolled cohort of 385 active
      military women in whom spectral analysis of continuous heart rate and variability
      was measured at 28 weeks' gestation. The primary outcome was the predictive value
      of spectral analysis of heart rate and blood pressure for hypertensive diseases
      of pregnancy. RESULTS: High-frequency heart rate variability was reduced and low
      frequency variability of systolic and diastolic blood pressure increased in women
      who would develop pregnancy-induced hypertension but not preeclampsia. Low
      frequency variability of diastolic blood pressure remained a significant
      predictor of pregnancy-induced hypertension but not preeclampsia after adjustment
      for age, weight, and blood pressure in a multivariate model. CONCLUSION: Early
      identification of pregnancy-induced hypertension can facilitate treatment to
      avoid maternal morbidity. Understanding the physiological underpinnings of the
      two very different diseases may lead to improved treatment and prevention. If
      proven effective in a broader population, the ability to differentiate pregnancy
      induced hypertension from preeclampsia may reduce unnecessary iatrogenic
      interventions or inappropriate preterm delivery.

PMID- 25970273
TI  - The Relation between Duration of Ruptured Membranes and Perinatal Outcome in
      Patients with Midtrimester Prelabor Rupture of Membranes.
AB  - OBJECTIVE: The aim of the study was to assess the impact of gestational age (GA)
      at rupture and latency on perinatal outcome after midtrimester prelabor rupture
      of membranes (PROM). STUDY DESIGN: We obtained data on singleton pregnancies from
      22 weeks onwards from the Dutch Perinatal Registry from 1999 to 2007, congenital
      abnormalities were excluded. In women with PROM before 26 weeks, we studied the
      impact of GA at rupture and latency on perinatal mortality and morbidity.
      RESULTS: A total of 1,233 pregnancies were included. Higher GA at delivery
      appeared to increase the probability of survival without morbidity, GA at PROM
      did not. In pregnancies of minimum 22 weeks GA, there appeared to be no clear
      relationship between earlier GA at PROM and adverse outcome. CONCLUSION: Longer
      latency and early GA at PROM seem to have limited impact in patients delivering
      after 22 weeks.

PMID- 25970274
TI  - De Novo Assembly and Characterization of Stress Transcriptome in a Salinity
      Tolerant Variety CS52 of Brassica juncea.
AB  - Oilseed mustard, Brassica juncea, exhibits high levels of genetic variability for
      salinity tolerance. To obtain the global view of transcriptome and investigate
      the molecular basis of salinity tolerance in a salt-tolerant variety CS52 of B.
      juncea, we performed transcriptome sequencing of control and salt-stressed
      seedlings. De novo assembly of 184 million high-quality paired-end reads yielded
      42,327 unique transcripts longer than 300 bp with RPKM >=1. When compared with
      non-redundant proteins, we could annotate 67% unigenes obtained in our study.
      Based on the mapping to expressed sequence tags (ESTs), 52.6% unigenes are novel
      compared to EST data available for B. juncea and constituent genomes.
      Differential expression analysis revealed altered expression of 1469 unigenes in
      response to salinity stress. Of these, 587, mainly associated with ROS
      detoxification, sulfur assimilation and calcium signaling pathways, are up
      regulated. Notable of these is RSA1 (SHORT ROOT IN SALT MEDIUM 1) INTERACTING
      TRANSCRIPTION FACTOR 1 (RITF1) homolog up regulated by >100 folds in response to
      stress. RITF1, encoding a bHLH transcription factor, is a positive regulator of
      SOS1 and several key genes involved in scavenging of salt stress-induced reactive
      oxygen species (ROS). Further, we performed comparative expression profiling of
      key genes implicated in ion homeostasis and sequestration (SOS1, SOS2, SOS3,
      ENH1, NHX1), calcium sensing pathway (RITF1) and ROS detoxification in
      contrasting cultivars for salinity tolerance, B. juncea and B. nigra. The results
      revealed higher transcript accumulation of most of these genes in B. juncea var.
      CS52 compared to salt-sensitive cultivar even under normal growth conditions.
      Together, these findings reveal key pathways and signaling components that
      contribute to salinity tolerance in B. juncea var. CS52. 

PMID- 25970275
TI  - Adverse reactions to antipsychotics in Parkinson disease: an analysis of the
      Spanish pharmacovigilance database.
AB  - PURPOSE: Although antipsychotics are well known for causing a plethora of adverse
      drug reactions (ADRs), the main concern when used to treat psychosis in Parkinson
      disease (PD) has traditionally been motor function worsening. The limited number
      of patients included in clinical trials contributes to underreport less common
      ADR. The aims of this study were to describe ADR to antipsychotics occurring in
      patients with PD notified to the Spanish Pharmacovigilance System and to contrast
      them with published reports. METHODS: All notifications from the Spanish
      Pharmacovigilance System for the last 30 years (1984-2014) where an antipsychotic
      was considered suspicious of the ADR in patients who were also on dopaminergic
      therapy were reviewed. In addition, a systematic search of MEDLINE (1966-2014)
      was conducted with the following Medical Subject Headings (MeSH) terms:
      "Parkinson disease" and "antipsychotic agents" or "psychotic disorders" and "drug
      related side effects" or "adverse reactions." RESULTS: Forty-four notifications
      were selected for evaluation. Quetiapine was the most frequently implicated drug
      since 2002, and previously clozapine was the drug implied in higher number of
      notifications. The most severe ADR was neuroleptic malignant syndrome, which was
      described in 5 patients (3 cases related to quetiapine, one to haloperidol, and
      another to olanzapine). CONCLUSIONS: Some previously unreported ADRs caused by
      antipsychotic drugs in patients with PD have been described for the first time in
      this study, although there are in general well-known antipsychotic adverse
      effects. It is remarkable that some notifications involve the use of drugs not
      recommended in these patients.

PMID- 25970276
TI  - How to manage thrombolysis interruptions in acute stroke?
AB  - OBJECTIVES: Tissue plasminogen activator (t-PA) is the only approved thrombolytic
      therapy for the treatment of stroke patients. Its effectiveness is highly time
      dependent because of the sensitivity of brain tissue to ischemia. Because of the
      short half-life of t-PA, it should be administered as a bolus followed by an
      immediate infusion. However, in clinical practice, there are sometimes delays
      between the application of the bolus and the start of the infusion; in addition,
      interruptions of the infusion may occur. There are no recommendations regarding
      how to handle such situations. METHODS: We simulate the effects on serum t-PA
      concentrations of different delays in administering t-PA using its known
      pharmacokinetic parameters in a 2-compartment model. RESULTS: Our results
      demonstrate that even short delays of only 1 minute between bolus and infusion
      severely affect serum t-PA concentrations. In addition, interruptions to the
      infusion that are over 1 minute in duration affect serum t-PA concentrations.
      CONCLUSIONS: These results strongly suggest avoiding bolus-infusion delays by
      giving the bolus only when the infusion is ready. In case of a delayed start of
      the infusion, the possibilities are restricted to do nothing or to give a second
      bolus. We have estimated the dosing of the second bolus depending on the duration
      of the delay/interruption to allow for the achievement of appropriate serum t-PA
      concentrations. However, clinical safety data are needed to recommend the
      application of a second bolus.

PMID- 25970277
TI  - Effective delivery of apomorphine in the management of Parkinson disease:
      practical considerations for clinicians and Parkinson nurses.
AB  - The clinical utility of long-term oral levodopa therapy in Parkinson disease (PD)
      is often limited by the emergence of motor complications. Over time, many
      patients with PD experience regular and/or unpredictable "off" periods, despite
      taking optimized oral medication regimens, with a major negative impact on their
      ability to undertake routine activities of daily living and consequently on their
      overall quality of life. One established approach for treating patients
      experiencing off periods and controlling motor fluctuations refractory to
      conventional oral drug therapy is the subcutaneous administration of the
      dopaminergic agonist apomorphine. This article outlines how the pharmacokinetic
      properties of apomorphine underpin its efficacy for the treatment of PD and
      provides practical guidance for the 3 main approaches in which it is used:
      subcutaneous intermittent apomorphine injection as a "rescue" therapy for off
      states, subcutaneous continuous apomorphine infusion for PD patients with
      intractable motor fluctuations as an alternative to other dopaminergic treatment,
      and in the apomorphine response (or challenge) test for assessment of dopamine
      induced motor response in patients thought to have PD, or in establishing the
      optimal tolerated dose of apomorphine in patients already known to have PD. Also
      discussed is the management of potential adverse events with subcutaneous
      administration of apomorphine, the majority of which are mild and easily managed
      in practice. The importance of a multidisciplinary PD team in the optimal
      management of PD patients is now recognized, in particular the role of the
      specialist PD nurse. 

PMID- 25970278
TI  - Pharmacological agents in aneurysmal subarachnoid hemorrhage: successes and
      failures.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating condition
      with high mortality. Proper management of this complex disease requires early
      surgical intervention followed by medical therapy. Pharmacological agents that
      unequivocally improve outcomes in aSAH are scarce. METHODS: The authors performed
      an exhaustive query of several databases including MEDLINE, the CENTRAL Register
      of Controlled Trials, and the Cochrane Database of Systematic Reviews for
      specific evidence on key medications that have been used in the treatment of
      aSAH. RESULTS: The bulk of the data available pertained to the following
      medications: calcium channel blockers, magnesium, statins, antifibrinolytics,
      aspirin, glucocorticoids, clazosentan, and tirilazad. Except for calcium channel
      blockers, the authors could not find any hard evidence that any of these agents
      affected outcome to a tangible degree. Aspirin may have some promise in
      prevention of aneurysm rupture and incidence of aSAH, but more substantive data
      are needed to conclusively corroborate this. CONCLUSIONS: Investigational efforts
      to attain outcome-modifying agents have had dubious results, but the inquest for
      discovery should not discontinue.

PMID- 25970279
TI  - Terazosin for the treatment of trauma-related nightmares: a report of 4 cases.
AB  - The selective alpha1-adrenergic antagonist prazosin has been shown in multiple
      studies to be effective in targeting trauma-related nightmares in posttraumatic
      stress disorder. There are limited data regarding the effectiveness of another
      selective alpha1-adrenergic antagonist terazosin for the treatment of trauma
      related nightmares. We present 4 cases in which terazosin was effectively used to
      treat nightmares as a second-line agent after prazosin failure. Further studies
      are needed to validate terazosin as an alternative to prazosin for the treatment
      of posttraumatic stress disorder-related nightmares. 

PMID- 25970280
TI  - Serotonin syndrome after electroconvulsive therapy in a patient on trazodone,
      bupropion, and quetiapine: a case report.
AB  - BACKGROUND: Serotonin syndrome is a potentially fatal complication that usually
      occurs in the combination use of several serotonergic agents. We presented a
      patient with major depressive disorder under the treatment of bupropion,
      trazodone, and quetiapine. Serotonin syndrome developed soon after she received
      the first session of electroconvulsive therapy (ECT). METHOD: This study is a
      case report. RESULTS: A 70-year-old female with major depressive disorder
      developed serotonin syndrome after the first session of ECT in combination with
      bupropion, trazodone, and quetiapine. Serotonin syndrome did not reappear in the
      subsequent ECT treatment while in the treatment with different therapeutic
      agents. CONCLUSIONS: The superimposing effect of ECT in conjunction with
      serotonergic agents might contribute to the development of serotonin syndrome.

PMID- 25970281
TI  - Risperidone as monotherapy for a patient with obsessive compulsive disorder
      comorbid with schizoaffective disorder: a case report.
AB  - Data on the efficacy of antipsychotics as monotherapy for obsessive-compulsive
      disorder (OCD) are inadequate. This report presents the case of a patient with
      OCD that was successfully treated with risperidone as monotherapy. Assessments
      revealed significant reductions in OCD symptoms after risperidone treatment (4
      mg/d). This report suggests the beneficial effect of risperidone for a patient
      with OCD comorbid with schizoaffective disorder. 

PMID- 25970282
TI  - Putamina involvement in Wernicke encephalopathy induced by Janus Kinase 2
      inhibitor.
AB  - OBJECTIVE: The aim of the study was to report a case of Wernicke encephalopathy
      (WE) due to fedratinib (Janus Kinase 2 inhibitor) treatment with atypical
      neuroimaging findings. METHODS: We present a detailed report of the case and
      literature review. RESULTS: A 68-year-old woman under treatment with fedratinib
      (investigational JAK2 inhibitor) developed memory impairment, diplopia, and
      ataxia compatible with WE. Brain magnetic resonance imaging showed extensive
      lesions involving medial thalami, periaqueductal gray, caudate nuclei, and
      putamina. Thiamine supplementation provided clinical recovery and radiological
      improvement of the lesions described. Basal ganglia lesions have been previously
      described in children with this disease, but this is rarely found in adults.
      Clinical trials including fedratinib have been recently discontinued, and its
      involvement in pathogenesis of WE may be related to thiamine-transporter
      inhibition. CONCLUSIONS: Our case represents an example of drug-related WE, with
      a rare radiological pattern. Precocious diagnosis and treatment are essential to
      prevent irreversible brain injury.

PMID- 25970283
TI  - Interferon-alpha caused reversible parkinsonism.
AB  - Interferon has been used to treat chronic viral hepatitis and several
      malignancies. However, it may cause various neuropsychiatric adverse effects
      including parkinsonism. We report a rare case of interferon alpha-2a therapy
      related parkinsonism in a 67-year-old man with metastatic papillary renal cell
      carcinoma and our experience of using Tc-99m-TRODAT-1 single photon emission
      computed tomography (SPECT) as a tool for evaluation of parkinsonism. Physicians
      should be alert to the possibility of interferon alpha-2a-related parkinsonism. 

PMID- 25970284
TI  - The effects of food limitation on life history tradeoffs in pregnant male gulf
      pipefish.
AB  - Syngnathid fishes (pipefishes, seahorses and seadragons) are characterized by a
      unique mode of paternal care in which embryos develop on or in the male's body,
      often within a structure known as a brood pouch. Evidence suggests that this
      pouch plays a role in mediating postcopulatory sexual selection and that males
      have some control over the events occurring within the pouch during the
      pregnancy. These observations lead to the prediction that males should invest
      differently in broods depending on the availability of food. Here, we use the
      Gulf pipefish to test this prediction by monitoring growth rate and offspring
      survivorship during the pregnancies of males under low- or high-food conditions.
      Our results show that pregnant males grow less rapidly on average than non
      pregnant males, and pregnant males under low-food conditions grow less than
      pregnant males under high-food conditions. Offspring survivorship, on the other
      hand, does not differ between food treatments, suggesting that male Gulf pipefish
      sacrifice investment in somatic growth, and thus indirectly sacrifice future
      reproduction, in favor of current reproduction. However, a positive relationship
      between number of failed eggs and male growth rate in our low-food treatments
      suggests that undeveloped eggs reduce the pregnancy's overall cost to the male
      compared to broods containing only viable offspring. 

PMID- 25970285
TI  - Correction: Rabies in nonhuman primates and potential for transmission to humans:
      a literature review and examination of selected French national data.

PMID- 25970286
TI  - There Is More than One Way to Crack an Oyster: Identifying Variation in Burmese
      Long-Tailed Macaque (Macaca fascicularis aurea) Stone-Tool Use.
AB  - We explored variation in patterns of percussive stone-tool use on coastal foods
      by Burmese long-tailed macaques (Macaca fascicularis aurea) from two islands in
      Laem Son National Park, Ranong, Thailand. We catalogued variation into three
      hammering classes and 17 action patterns, after examining 638 tool-use bouts
      across 90 individuals. Hammering class was based on the stone surface used for
      striking food, being face, point, and edge hammering. Action patterns were
      discriminated by tool material, hand use, posture, and striking motion. Hammering
      class was analyzed for associations with material and behavioural elements of
      tool use. Action patterns were not, owing to insufficient instances of most
      patterns. We collected 3077 scan samples from 109 macaques on Piak Nam Yai
      Island's coasts, to determine the proportion of individuals using each hammering
      class and action pattern. Point hammering was significantly more associated with
      sessile foods, smaller tools, faster striking rates, smoother recoil, unimanual
      use, and more varied striking direction, than were face and edge hammering, while
      both point and edge hammering were significantly more associated with precision
      gripping than face hammering. Edge hammering also showed distinct differences
      depending on whether such hammering was applied to sessile or unattached foods,
      resembling point hammering for sessile foods and face hammering for unattached
      foods. Point hammering and sessile edge hammering compared to prior descriptions
      of axe hammering, while face and unattached edge hammering compared to pound
      hammering. Analysis of scans showed that 80% of individuals used tools, each
      employing one to four different action patterns. The most common patterns were
      unimanual point hammering (58%), symmetrical-bimanual face hammering (47%) and
      unimanual face hammering (37%). Unimanual edge hammering was relatively frequent
      (13%), compared to the other thirteen rare action patterns (<5%). We compare our
      study to other stone-using primates, and discuss implications for further
      research. 

PMID- 25970288
TI  - Correction: The Singapore Liver Cancer Recurrence (SLICER) Score for Relapse
      Prediction in Patients with Surgically Resected Hepatocellular Carcinoma.

PMID- 25970287
TI  - Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In
      Vitro and In Vivo.
AB  - Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are
      important causative agents of respiratory tract infections. Both pathogens are
      associated with seasonal disease outbreaks in the pediatric population, and can
      often be detected simultaneously in infants hospitalized with bronchiolitis or
      pneumonia. It has been described that respiratory virus infections may predispose
      for bacterial superinfections, resulting in severe disease. However, studies on
      the influence of bacterial colonization of the upper respiratory tract on the
      pathogenesis of subsequent respiratory virus infections are scarce. Here, we have
      investigated whether pneumococcal colonization enhances subsequent HRSV
      infection. We used a newly generated recombinant subgroup B HRSV strain that
      expresses enhanced green fluorescent protein and pneumococcal isolates obtained
      from healthy children in disease-relevant in vitro and in vivo model systems.
      Three pneumococcal strains specifically enhanced in vitro HRSV infection of
      primary well-differentiated normal human bronchial epithelial cells grown at air
      liquid interface, whereas two other strains did not. Since previous studies
      reported that bacterial neuraminidase enhanced HRSV infection in vitro, we
      measured pneumococcal neuraminidase activity in these cultures but found no
      correlation with the observed infection enhancement in our model. Subsequently, a
      selection of pneumococcal strains was used to induce nasal colonization of cotton
      rats, the best available small animal model for HRSV. Intranasal HRSV infection
      three days later resulted in strain-specific enhancement of HRSV replication in
      vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was
      also associated with enhanced syncytium formation in vivo. However, neither
      pneumococci nor HRSV were found to spread from the upper to the lower respiratory
      tract, and neither pathogen was transmitted to naive cage mates by direct
      contact. These results demonstrate that pneumococcal colonization can enhance
      subsequent HRSV infection, and provide tools for additional mechanistic and
      intervention studies. 

PMID- 25970289
TI  - Climate Effects on High Latitude Daphnia via Food Quality and Thresholds.
AB  - Climate change is proceeding rapidly at high northern latitudes and may have a
      variety of direct and indirect effects on aquatic food webs. One predicted effect
      is the potential shift in phytoplankton community structure towards increased
      cyanobacterial abundance. Given that cyanobacteria are known to be a
      nutritionally poor food source, we hypothesized that such a shift would reduce
      the efficiency of feeding and growth of northern zooplankton. To test this
      hypothesis, we first isolated a clone of Daphnia pulex from a permafrost thaw
      pond in subarctic Quebec, and confirmed that it was triploid but otherwise
      genetically similar to a diploid, reference clone of the same species isolated
      from a freshwater pond in southern Quebec. We used a controlled flow-through
      system to investigate the direct effect of temperature and indirect effect of
      subarctic picocyanobacteria (Synechococcus) on threshold food concentrations and
      growth rate of the high latitude clone. We also compared the direct effect of
      temperature on both Daphnia clones feeding on eukaryotic picoplankton
      (Nannochloropsis). The high latitude clone had a significantly lower food
      threshold for growth than the temperate clone at both 18 and 26 degrees C,
      implying adaptation to lower food availability even under warmer conditions.
      Polyunsaturated fatty acids were present in the picoeukaryote but not the
      cyanobacterium, confirming the large difference in food quality. The food
      threshold for growth of the high latitude Daphnia was 3.7 (18 degrees C) to 4.2
      (26 degrees C) times higher when fed Synechococcus versus Nannochloropsis, and
      there was also a significant negative effect of increased temperature and
      cyanobacterial food on zooplankton fatty acid content and composition. The
      combined effect of temperature and food quality on the performance of the high
      latitude Daphnia was greater than their effects added separately, further
      indicating the potentially strong indirect effects of climate warming on aquatic
      food web processes. 

PMID- 25970291
TI  - Relative Abundance and Plasmodium Infection Rates of Malaria Vectors in and
      around Jabalpur, a Malaria Endemic Region in Madhya Pradesh State, Central India.
AB  - BACKGROUND: This study was undertaken in two Primary Health Centers (PHCs) of
      malaria endemic district Jabalpur in Madhya Pradesh (Central India). METHODS: In
      this study we had investigated the relative frequencies of the different
      anopheline species collected within the study areas by using indoor resting
      catches, CDC light trap and human landing methods. Sibling species of malaria
      vectors were identified by cytogenetic and molecular techniques. The role of each
      vector and its sibling species in the transmission of the different Plasmodium
      species was ascertained by using sporozoite ELISA. RESULTS: A total of 52,857
      specimens comprising of 17 anopheline species were collected by three different
      methods (39,964 by indoor resting collections, 1059 by human landing and 11,834
      by CDC light trap). Anopheles culicifacies was most predominant species in all
      collections (55, 71 and 32% in indoor resting, human landing and light trap
      collections respectively) followed by An. subpictus and An. annularis. All five
      sibling species of An. culicifacies viz. species A, B, C, D and E were found
      while only species T and S of An. fluviatilis were collected. The overall
      sporozoite rate in An. culicifacies and An. fluviatilis were 0.42% (0.25% for P.
      falciparum and 0.17% for P. vivax) and 0.90% (0.45% for P. falciparum and 0.45%
      for P. vivax) respectively. An. culicifacies and An. fluviatilis were found
      harbouring both P. vivax variants VK-210 and VK-247, and P. falciparum. An.
      culicifacies sibling species C and D were incriminated as vectors during most
      part of the year while sibling species T of An. fluviatilis was identified as
      potential vector in monsoon and post monsoon season. CONCLUSIONS: An.
      culicifacies species C (59%) was the most abundant species followed by An.
      culicifacies D (24%), B (8.7%), E (6.7%) and A (1.5%). Among An. fluviatilis
      sibling species, species T was common (99%) and only few specimens of S were
      found. Our study provides crucial information on the prevalence of An.
      culicifacies and An. fluviatilis sibling species and their potential in malaria
      transmission which will assist in developing strategic control measures against
      these vectors.

PMID- 25970290
TI  - TGF-Beta Negatively Regulates the BMP2-Dependent Early Commitment of Periodontal
      Ligament Cells into Hard Tissue Forming Cells.
AB  - Transforming growth factor beta (TGF-beta) is a multi-functional growth factor
      expressed in many tissues and organs. Genetic animal models have revealed the
      critical functions of TGF-beta in craniofacial development, including the teeth
      and periodontal tissue. However, the physiological function of TGF-beta in the
      periodontal ligament (PDL) has not been fully elucidated. In this study, we
      examined the roles of TGF-beta in the cytodifferentiation of PDL cells using a
      TGF-beta receptor kinase inhibitor, SB431542. Mouse PDL cell clones (MPDL22) were
      cultured in calcification-inducing medium with or without SB431542 in the
      presence or absence of various growth factors, such as bone morphogenetic protein
      (BMP)-2, TGF-beta and fibroblast growth factor (FGF)-2. SB431542 dramatically
      enhanced the BMP-2-dependent calcification of MPDL22 cells and accelerated the
      expression of ossification genes alkaline phosphatase (ALPase) and Runt-related
      transcription factor (Runx) 2 during early osteoblastic differentiation. SB431542
      did not promote MPDL22 calcification without BMP-2 stimulation. The cell growth
      rate and collagen synthesis during the late stage of MPDL22 culture were retarded
      by SB431542. Quantitative reverse transcription polymerase chain reaction
      analysis revealed that the expressions of Smurf1 and Smad6, which are negative
      feedback components in the TGF-beta/BMP signaling pathway, were downregulated in
      MPDL22 cells with SB431542 treatment. These results suggest that an endogenous
      signal from TGF-beta negatively regulates the early commitment and
      cytodifferentiation of PDL cells into hard tissue-forming cells. A synthetic drug
      that regulates endogenous TGF-beta signals may be efficacious for developing
      periodontal regenerative therapies. 

PMID- 25970292
TI  - Novel antimicrobial peptides with high anticancer activity and selectivity.
AB  - We describe a strategy to boost anticancer activity and reduce normal cell
      toxicity of short antimicrobial peptides by adding positive charge amino acids
      and non-nature bulky amino acid beta-naphthylalanine residues to their termini.
      Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and
      less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1.
      Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1
      preferentially binds cancer cells and causes apoptotic cell death. Moreover, a
      significant inhibition in human lung tumor growth was observed in the xenograft
      mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the
      development of highly effective and selective antimicrobial and anticancer
      peptide-based therapeutics. 

PMID- 25970293
TI  - Effectiveness of protected areas for representing species and populations of
      terrestrial mammals in Costa Rica.
AB  - Costa Rica has one of the greatest percentages (26%) of protected land in the
      world. The National Protected Areas System (NPAS) of Costa Rica was established
      in 1976 and currently includes >190 protected areas within seven different
      protection categories. The effectiveness of the NPAS to represent species,
      populations, and areas with high species richness has not been properly
      evaluated. Such evaluations are fundamental to understand what is necessary to
      strengthen the NPAS and better protect biodiversity. We present a novel
      assessment of NPAS effectiveness in protecting mammal species. We compiled the
      geographical ranges of all terrestrial Costa Rican mammals then determined
      species lists for all protected areas and the estimated proportion of each
      species' geographic range protected. We also classified mammal species according
      to their conservation status using the IUCN Red List of Threatened Species. We
      found almost complete representation of mammal species (98.5%) in protected
      areas, but low relative coverage (28.3% on average) of their geographic ranges in
      Costa Rica and 25% of the species were classified as underprotected according to
      a priori representation targets. Interestingly, many species-rich areas are not
      protected, and at least 43% of cells covering the entire country are not included
      in protected areas. Though protected areas in Costa Rica represent species
      richness well, strategic planning for future protected areas to improve species
      complementarity and range protection is necessary. Our results can help to define
      sites where new protected areas can have a greater impact on mammal conservation,
      both in terms of species richness and range protection. 

PMID- 25970294
TI  - Population-Wide Failure to Breed in the Clark's Nutcracker (Nucifraga
      columbiana).
AB  - In highly variable environments, conditions can be so stressful in some years
      that entire populations forgo reproduction in favor of higher likelihood of
      surviving to breed in future years. In two out of five years, Clark's nutcrackers
      (Nucifraga Columbiana) in the Greater Yellowstone Ecosystem exhibited population
      wide failure to breed. Clark's nutcrackers at the study site experienced
      substantial interannual differences in food availability and weather conditions,
      and the two nonbreeding years corresponded with low whitebark pine (Pinus
      albicaulis) cone crops the previous autumn (<= an average of 8 +/- 2 cones per
      tree versus >= an average of 20 +/- 2 cones per tree during breeding years) and
      high snowpack in early spring (>= 61.2 +/- 5.5 cm versus <= 51.9 +/- 4.4 cm
      during breeding years). The average adult body condition index during the
      breeding season was significantly lower in 2011 (-1.5 +/- 1.1), a nonbreeding
      year, as compared to 2012 (6.2 +/- 2.0), a breeding year. The environmental cues
      available to the birds prior to breeding, specifically availability of cached
      whitebark pine seeds, may have allowed them to predict that breeding conditions
      would be poor, leading to the decision to skip breeding. Alternatively, the
      Clark's nutcrackers may have had such low body energy stores that they chose not
      to or were unable to breed. Breeding plasticity would allow Clark's nutcrackers
      to exploit an unpredictable environment. However, if large-scale mortality of
      whitebark pines is leading to an increase in the number of nonbreeding years,
      there could be serious population-level and ecosystem-wide consequences. 

PMID- 25970295
TI  - Human Urine Derived Stem Cells in Combination with beta-TCP Can Be Applied for
      Bone Regeneration.
AB  - Bone tissue engineering requires highly proliferative stem cells that are easy to
      isolate. Human urine stem cells (USCs) are abundant and can be easily harvested
      without using an invasive procedure. In addition, in our previous studies, USCs
      have been proved to be able to differentiate into osteoblasts, chondrocytes, and
      adipocytes. Therefore, USCs may have great potential and advantages to be applied
      as a cell source for tissue engineering. However, there are no published studies
      that describe the interactions between USCs and biomaterials and applications of
      USCs for bone tissue engineering. Therefore, the objective of the present study
      was to evaluate the interactions between USCs with a typical bone tissue
      engineering scaffold, beta-Tricalcium Phosphate (beta-TCP), and to determine
      whether the USCs seeded onto beta-TCP scaffold can promote bone regeneration in a
      segmental femoral defect of rats. Primary USCs were isolated from urine and
      seeded on beta-TCP scaffolds. Results showed that USCs remained viable and
      proliferated within beta-TCP. The osteogenic differentiation of USCs within the
      scaffolds was demonstrated by increased alkaline phosphatase activity and calcium
      content. Furthermore, beta-TCP with adherent USCs (USCs/beta-TCP) were implanted
      in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration
      was determined using X-ray, micro-CT, and histologic analyses. Results further
      demonstrated that USCs in the scaffolds could enhance new bone formation, which
      spanned bone defects in 5 out of 11 rats while beta-TCP scaffold alone induced
      modest bone formation. The current study indicated that the USCs can be used as a
      cell source for bone tissue engineering as they are compatible with bone tissue
      engineering scaffolds and can stimulate the regeneration of bone in a critical
      size bone defect. 

PMID- 25970297
TI  - Identification of inversion domains in KTiOPO4 via resonant X-ray diffraction.
AB  - A novel method is presented for the identification of the absolute
      crystallographic structure in multi-domain polar materials such as ferroelectric
      KTiOPO4. Resonant (or 'anomalous') X-ray diffraction spectra collected across the
      absorption K edge of Ti (4.966 keV) on a single Bragg reflection demonstrate a
      huge intensity ratio above and below the edge, providing a polar domain contrast
      of ~270. This allows one to map the spatial domain distribution in a periodically
      inverted sample, with a resolution of ~1 um achieved with a microfocused beam.
      This non-contact, non-destructive technique is well suited for samples of large
      dimensions (in contrast with traditional resonant X-ray methods based on
      diffraction from Friedel pairs), and its potential is particularly relevant in
      the context of physical phenomena connected with an absence of inversion
      symmetry, which require characterization of the underlying absolute atomic
      structure (such as in the case of magnetoelectric coupling and multiferroics).

PMID- 25970298
TI  - Theoretical study of the properties of X-ray diffraction moire fringes. I.
AB  - A detailed and comprehensive theoretical description of X-ray diffraction moire
      fringes for a bicrystal specimen is given on the basis of a calculation by plane
      wave dynamical diffraction theory. Firstly, prior to discussing the main subject
      of the paper, a previous article [Yoshimura (1997). Acta Cryst. A53, 810-812] on
      the two-dimensionality of diffraction moire patterns is restated on a thorough
      calculation of the moire interference phase. Then, the properties of moire
      fringes derived from the above theory are explained for the case of a plane-wave
      diffraction image, where the significant effect of Pendellosung intensity
      oscillation on the moire pattern when the crystal is strained is described in
      detail with theoretically simulated moire images. Although such plane-wave moire
      images are not widely observed in a nearly pure form, knowledge of their
      properties is essential for the understanding of diffraction moire fringes in
      general. 

PMID- 25970299
TI  - Response to Letter Regarding Instant Cage Making Using PMMA.

PMID- 25970300
TI  - The Structure of the Narcissistic Personality Inventory With Binary and Rating
      Scale Items.
AB  - Narcissistic Personality Inventory (NPI) items typically have a forced-choice
      format, comprising a narcissistic and a nonnarcissistic statement. Recently, some
      have presented the narcissistic statements and asked individuals to either
      indicate whether they agree or disagree that the statements are self-descriptive
      (i.e., a binary response format) or to rate the extent to which they agree or
      disagree that these statements are self-descriptive on a Likert scale (i.e., a
      rating response format). The current research demonstrates that when NPI items
      have a binary or a rating response format, the scale has a bifactor structure
      (i.e., the items load on a general factor and on 6 specific group factors).
      Indexes of factor strength suggest that the data are unidimensional enough for
      the NPI's general factor to be considered a measure of a narcissism latent trait.
      However, the rating item general factor assessed more narcissism components than
      the binary item one. The positive correlations of the NPI's general factor,
      assessed when items have a rating response format, were moderate with self
      esteem, strong with a measure of narcissistic grandiosity, and weak with 2
      measures of narcissistic vulnerability. Together, the results suggest that using
      a rating format for items enhances the information provided by the NPI. 

PMID- 25970296
TI  - Interplay between transcriptional control and chromatin regulation in the
      oligodendrocyte lineage.
AB  - The recent years have been characterized by a surge of studies on the role of
      transcription factors and histone modifications in regulating the progression of
      progenitors into oligodendrocytes. This review summarizes this body of evidence
      and presents an integrated view of transcriptional networks and epigenetic
      regulators defining proliferating progenitors and their differentiation along the
      oligodendrocyte lineage. We suggest that transcription factors in proliferating
      progenitors have direct access to DNA, due to predominantly euchromatic nuclei.
      As progenitors differentiate, however, transcriptional competence is modulated by
      the formation of heterochromatin, which modifies the association of DNA with
      nucleosomal histones and renders the access of transcription factors dependent on
      the activity of epigenetic modulators. These concepts are delineated within the
      context of development, and the potential functional implications are discussed.

PMID- 25970301
TI  - A hybrid-membrane migration method to isolate high-purity adipose-derived stem
      cells from fat tissues.
AB  - Human adipose-derived stem cells (hADSCs) exhibit heterogeneous characteristics,
      indicating various genotypes and differentiation abilities. The isolated hADSCs
      can possess different purity levels and divergent properties depending on the
      purification methods used. We developed a hybrid-membrane migration method that
      purifies hADSCs from a fat tissue solution with extremely high purity and
      pluripotency. A primary fat-tissue solution was permeated through the porous
      membranes with a pore size from 8 to 25 MUm, and the membranes were incubated in
      cell culture medium for 15-18 days. The hADSCs that migrated from the membranes
      contained an extremely high percentage (e.g., >98%) of cells positive for
      mesenchymal stem cell markers and showed almost one order of magnitude higher
      expression of some pluripotency genes (Oct4, Sox2, Klf4 and Nanog) compared with
      cells isolated using the conventional culture method.

PMID- 25970303
TI  - Quantitative assessment of binding affinities for nanoparticles targeted to
      vulnerable plaque.
AB  - Recent successes in targeted immune and cell-based therapies have driven new
      directions for pharmaceutical research. With the rise of these new therapies
      there is an unfilled need for companion diagnostics to assess patients' potential
      for therapeutic response. Targeted nanomaterials have been widely investigated to
      fill this niche; however, in contrast to small molecule or peptide-based targeted
      agents, binding affinities are not reported for nanomaterials, and to date there
      has been no standard, quantitative measure for the interaction of targeted
      nanoparticle agents with their targets. Without a standard measure, accurate
      comparisons between systems and optimization of targeting behavior are
      challenging. Here, we demonstrate a method for quantitative assessment of the
      binding affinity for targeted nanoparticles to cell surface receptors in living
      systems and apply it to optimize the development of a novel targeted nanoprobe
      for imaging vulnerable atherosclerotic plaques. In this work, we developed
      sulfated dextran-coated iron oxide nanoparticles with specific targeting to
      macrophages, a cell type whose density strongly correlates with plaque
      vulnerability. Detailed quantitative, in vitro characterizations of (111)In(3+)
      radiolabeled probes show high-affinity binding to the macrophage scavenger
      receptor A (SR-A). Cell uptake studies illustrate that higher surface sulfation
      levels result in much higher uptake efficiency by macrophages. We use a modified
      Scatchard analysis to quantitatively describe nanoparticle binding to targeted
      receptors. This characterization represents a potential new standard metric for
      targeted nanomaterials. 

PMID- 25970305
TI  - Association of HIV Infection With Anal and Penile Low-Risk Human Papillomavirus
      Infections Among Men Who Have Sex With Men in Amsterdam: The HIV & HPV in MSM
      Study.
AB  - BACKGROUND: This study among men who have sex with men (MSM) aimed to (1) assess
      prevalence of anogenital low-risk human papillomavirus (lrHPV) infections, (2)
      evaluate associations with HIV infection, and (3) investigate lrHPV concordance.
      METHODS: In 2010 to 2011, MSM 18 years or older were recruited in Amsterdam, the
      Netherlands, and provided anal and penile self-swabs (HIV & HPV in MSM study).
      Using the HPV SPF10-PCR/DEIA/LiPA25 system, the presence of lrHPV types 6, 11,
      34, 40, 42, 43, 44, 53, 54, 66, 68/73, 70, and 74 could be detected. Logistic
      regression with generalized estimating equations was used to assess the
      independent effect of HIV on lrHPV infections. The model was repeated for lrHPV
      subcategories (nononcogenic and weakly oncogenic infections separately).
      Concordance was defined as detection of the same lrHPV type in both self-swabs of
      one individual. RESULTS: A total of 778 MSM were included, of whom 317 (41%) were
      HIV positive (median CD4 count at enrollment, 530 cells/mm). Prevalence of anal
      lrHPV was 45% (95% confidence interval [CI], 41%-50%) in HIV-negative MSM and 69%
      (95% CI, 64%-74%) in HIV-positive MSM. Prevalence of penile lrHPV was 20% (95%
      CI, 16%-24%) and 37% (95% CI, 31%-42%), respectively. In multivariable analysis,
      HIV infection was independently associated with anal (adjusted odds ratio [aOR],
      1.9; 95% CI, 1.5-2.3) and penile lrHPV (aOR, 2.0; 95% CI, 1.4-2.7). Nononcogenic
      and weakly oncogenic lrHPV subcategories showed a similar pattern of association.
      Anal lrHPV infections were strongly associated with the presence of a type
      concordant penile infection (aOR, 5.8; 95% CI, 4.4-7.5) and vice versa (aOR, 5.7;
      95% CI, 4.4-7.5). CONCLUSIONS: Anal and penile infections with lrHPV are common
      in MSM. HIV infection was an independent determinant for lrHPV infections.

PMID- 25970306
TI  - The Role of Chlamydia trachomatis in High-Risk Human Papillomavirus Persistence
      Among Female Sex Workers in Nairobi, Kenya.
AB  - BACKGROUND: Little is known about risk factors for persistent high-risk human
      papillomavirus (hrHPV) infection in low-income settings, and prior research has
      not quantified the relative duration of hrHPV infections stratified by risk
      factors. We compared the duration of hrHPV infection among female sex workers
      (FSWs) by exposure to sexually transmitted infections (STIs), using a highly
      sensitive biomarker assay. METHODS: From 2009 to 2011, 350 FSWs enrolled in this
      longitudinal study. Every 3 months, sociodemographic and sexual behavior data
      were collected via questionnaire, and APTIMA assays were used to detect the rRNA
      of Chlamydia trachomatis (CT), Neisseria gonorrhea, Trichomonas vaginalis,
      Mycoplasma genitalium, and messenger RNA of the E6/E7 oncoproteins expressed by
      hrHPV. Among 173 FSW who were infected with hrHPV during the observation period,
      accelerated failure time models estimated time ratios (TRs) for duration of hrHPV
      infection, comparing FSW infected with STIs at baseline to STI-uninfected FSWs.
      RESULTS: Median follow-up time was 26.2 months (interquartile range, 18.8-27.5
      months). The median duration of hrHPV infection among all FSWs was 9.3 months
      (95% confidence interval [CI], 9.3-11.5). The duration of hrHPV infection among
      FSW infected with CT at baseline was greater than that among FSWs who were
      uninfected (adjusted TR, 1.7; 95% CI, 1.2-2.6). Among FSWs who were coinfected
      with hrHPV and CT at baseline, the adjusted TR was 3.4 (95% CI, 2.5-5.4) compared
      with FSWs infected with hrHPV only. No other STI was associated with hrHPV
      duration. CONCLUSIONS: Recent or concurrent CT infection was associated with
      prolonged hrHPV infection among a cohort of Nairobi FSWs. Management of CT could
      reduce risk for hrHPV persistence.

PMID- 25970307
TI  - Structural determinants of inconsistent condom use with clients among migrant sex
      workers: findings of longitudinal research in an urban canadian setting.
AB  - BACKGROUND: Migrant women in sex work experience unique risks and protective
      factors related to their sexual health. Given the dearth of knowledge in high
      income countries, we explored factors associated with inconsistent condom use by
      clients among migrant female sex workers over time in Vancouver, BC. METHODS:
      Questionnaire and HIV/sexually transmitted infection testing data from a
      longitudinal cohort, An Evaluation of Sex Workers Health Access, were collected
      from 2010 to 2013. Logistic regression using generalized estimating equations was
      used to model correlates of inconsistent condom use by clients among
      international migrant sex workers over a 3-year study period. RESULTS: Of 685
      participants, analyses were restricted to 182 (27%) international migrants who
      primarily originated from China. In multivariate generalized estimating equations
      analyses, difficulty accessing condoms (adjusted odds ratio [AOR], 3.76; 95%
      confidence interval [CI], 1.13-12.47) independently correlated with increased
      odds of inconsistent condom use by clients. Servicing clients in indoor sex work
      establishments (e.g., massage parlors) (AOR, 0.34; 95% CI, 0.15-0.77), and high
      school attainment (AOR, 0.22; 95% CI, 0.09-0.50) had independent protective
      effects on the odds of inconsistent condom use by clients. CONCLUSIONS: Findings
      of this longitudinal study highlight the persistent challenges faced by migrant
      sex workers in terms of accessing and using condoms. Migrant sex workers who
      experienced difficulty in accessing condoms were more than 3 times as likely to
      report inconsistent condom use by clients. Laws, policies, and programs promoting
      access to safer, decriminalized indoor work environments remain urgently needed
      to promote health, safety, and human rights for migrant workers in the sex
      industry.

PMID- 25970308
TI  - Condomless Anal Intercourse Among Males and Females at High Risk for Heterosexual
      HIV Infection.
AB  - BACKGROUND: Understanding and addressing heterosexual HIV transmission requires
      attention to the range and context of heterosexual sexual behaviors. We sought to
      determine population-based prevalence of condomless anal intercourse (CAI) among
      individuals at increased heterosexual HIV risk in Baltimore and to identify
      demographic, behavioral, and health-related correlates. METHODS: Data were from a
      cross-sectional study of 185 males and 198 females at increased heterosexual risk
      for HIV recruited using respondent-driven sampling as part of Centers for Disease
      Control and Prevention's National HIV Behavioral Surveillance Project in
      Baltimore, August-December 2010. Bivariate and multivariate logistic regression
      examined factors associated with heterosexual CAI. RESULTS: The sample was
      majority African American, with a mean age of 38 years among men and 34 years
      among women. Forty-two percent of men (95% confidence interval, 30.9%-52.0%) and
      38% of women (95% confidence interval, 29.4%-47.2%) reported any CAI in the past
      year, with variance by partner type and sex. Among men, CAI was significantly
      associated with homelessness, casual and exchange partners, same-sex partner in
      past year, and substance use. Among women, CAI was significantly associated with
      lower education, casual and exchange partners, same-sex partner in past year,
      multiple partners, and substance use. In adjusted sex-specific models, males and
      females with increasing numbers of partners were more likely to engage in CAI.
      CONCLUSIONS: It is important to recognize the efficiency of transmission of HIV
      and other sexually transmitted infections through CAI. There is a need to broaden
      heterosexual sexual health promotion and HIV/sexually transmitted infection
      prevention to adequately and appropriately address risks and prevention
      strategies for anal intercourse.

PMID- 25970310
TI  - What can we infer about incarceration and sexually transmitted diseases?

PMID- 25970309
TI  - Male Incarceration Rates and Rates of Sexually Transmitted Infections: Results
      From a Longitudinal Analysis in a Southeastern US City.
AB  - BACKGROUND: In the United States, rates of certain sexually transmitted
      infections (STIs) are increasing. Contextual factors seem to play an important
      role in shaping STI transmission dynamics. This longitudinal study explores the
      relationship between one contextual determinant of health (the male incarceration
      rate) and rates of newly diagnosed STIs in census tracts in Atlanta, GA. METHODS:
      The sample consisted of all census tracts in Atlanta (n = 946). Annual data on
      STI diagnoses were drawn from the Georgia surveillance system for 2005 to 2010;
      annual male incarceration data were drawn from the Georgia Department of
      Corrections for 2005 to 2010; and data on potential confounders were drawn from
      the US Census. Multivariable growth models were used to examine the association
      between the male incarceration rate and rates of newly diagnosed STIs,
      controlling for covariates. RESULTS: Census tracts with higher baseline male
      incarceration rates had a higher baseline rate of newly diagnosed STIs. Census
      tracts with increasing male incarceration rates experienced a more rapid increase
      in their rate of newly diagnosed STIs. Census tracts with medium and high
      baseline male incarceration rates experienced a decrease in their rate of newly
      diagnosed STIs over time. CONCLUSIONS: The present study strengthens the evidence
      that male incarceration rates have negative consequences on sexual health
      outcomes, although the relationship may be more nuanced than originally thought.
      Future multilevel research should explore individual sexual risk behaviors and
      networks in the context of high male incarceration rates to better understand how
      male incarceration shapes rates of STIs.

PMID- 25970311
TI  - Gonorrhea Treatment Failures With Oral and Injectable Expanded Spectrum
      Cephalosporin Monotherapy vs Dual Therapy at 4 Canadian Sexually Transmitted
      Infection Clinics, 2010-2013.
AB  - BACKGROUND: Antimicrobial resistance has developed to all antibiotics used to
      treat gonorrhea (GC), and trends in GC antimicrobial resistance have prompted
      changes in treatment guidelines. We examined treatment failures in sexually
      transmitted infection clinics. METHODS: Four Canadian sexually transmitted
      infection clinics reviewed treatment regimens, minimum inhibitory concentrations
      for cephalosporins and azithromycin, anatomical infection sites, and treatment
      outcomes for GC infections between January 2010 and September 2013, in
      individuals who returned for test of cure within 30 days of treatment. Treatment
      failure was defined as the absence of reported sexual contact during the
      posttreatment period and (i) positive for Neisseria gonorrhoeae on culture of
      specimens taken at least 72 hours after treatment or (ii) positive nucleic acid
      amplification test specimens taken at least 2 to 3 weeks after treatment, and
      matching sequence type pretreatment and posttreatment. chi Test and Fisher exact
      test were used to assess association of categorical variables. RESULTS: Of 389
      specimens reviewed, GC treatment failures occurred in 13 specimens treated with
      cefixime 400-mg single dose (17.8% treatment failure rate regardless of
      anatomical site) and in 1 oropharyngeal specimen treated with cefixime 800-mg
      single dose. No treatment failures occurred using either ceftriaxone monotherapy
      or cefixime/ceftriaxone combined with azithromycin or doxycycline. CONCLUSIONS:
      In contrast to oral cefixime monotherapy, no treatment failures were identified
      with injectable ceftriaxone monotherapy or combination GC treatment. Our data
      support the use of combination treatment of GC with an extended spectrum
      cephalosporin (including oral cefixime) with azithromycin or doxycycline as well
      as ceftriaxone monotherapy.

PMID- 25970312
TI  - High Prevalence of Azithromycin-Resistant Neisseria gonorrhoeae Isolates With a
      Multidrug Resistance Phenotype in Fukuoka, Japan.
AB  - BACKGROUND: The current guidelines recommend a combination of ceftriaxone and
      azithromycin as a first-line treatment of gonorrhea in the United States and
      Europe. Despite not being recommended as a first-line regimen in Japan, an oral 2
      g dose of azithromycin did become available for gonococcal infections in 2009.
      Recently, the emergence of azithromycin-resistant Neisseria gonorrhoeae isolates
      has been reported in several countries, including Japan. METHODS: Antimicrobial
      susceptibility testing was performed on a total of 677 clinical isolates of N.
      gonorrhoeae obtained from January 2010 to December 2013 in Fukuoka, Japan. A
      molecular analysis by N. gonorrhoeae multiantigen sequence typing was conducted
      on the azithromycin-resistant isolates. RESULTS: The proportion of azithromycin
      resistant isolates (minimum inhibitory concentration > 0.5 MUg/mL) increased
      significantly from 1.8% in 2010 to 22.6% in 2013 (P < 0.001). Among 50
      azithromycin-resistant isolates, 30 (60%) exhibited a resistant phenotype to
      multiple drugs including cefixime. The 2 predominant sequence types (STs)
      identified by N. gonorrhoeae multiantigen sequence typing were ST6798 (por allele
      4033 and tbpB allele 110) and ST1407 (por allele 908 and tbpB allele 110) at
      40.0% (20/50) and 12.0% (6/50), respectively. There was a statistically
      significant increase of the proportion of ST6798 from 0% (0/19) in 2010-2012 to
      64.5% (20/31) in 2013 (P < 0.001). CONCLUSIONS: Over the previous 4 years, an
      increasing prevalence of azithromycin-resistant N. gonorrhoeae isolates with a
      multidrug-resistant phenotype was observed. Furthermore, the azithromycin
      resistant isolates seemed to belong to 2 predominant STs. As a result, continued
      surveillance of gonococci resistant to antimicrobial agents, including
      azithromycin in Fukuoka, Japan, is necessary.

PMID- 25970313
TI  - Human papillomavirus type 16 sequence variation in concurrent vulvar and penile
      carcinoma in a married couple.
AB  - We encountered an elderly married couple with concurrent vulvar and penile
      carcinoma with an Asian variant of human papillomavirus type 16. Asian variants
      might have an elevated risk of concurrent external genital carcinomas of a male
      and a female, and analysis of human papillomavirus variants might be important to
      understand the mechanism of carcinogenesis. 

PMID- 25970314
TI  - Shigella flexneri: A Cause of Significant Morbidity and Associated With Sexually
      Transmitted Infections in Men Who Have Sex With Men.

PMID- 25970315
TI  - Neurosyphilis initially presenting as hemorrhagic exudative optic neuropathy in
      an immunocompetent patient.
AB  - We describe an unusual case of hemorrhagic exudative optic neuropathy as an
      initial presentation of neurosyphilis in an immunocompetent patient. The
      clinicians have to be alert to consider a diagnosis of syphilitic optic
      neuropathy in cases with hemorrhagic exudative optic neuropathy. 

PMID- 25970316
TI  - Neurosyphilis and ophthalmic syphilis in persons with negative rapid plasma
      reagin and positive treponemal antibody test results.
AB  - The detection of serodiscordant syphilis test results raises several important
      clinical and public health questions. Based on our retrospective review, the
      probability of neurosyphilis in persons with serodiscordant serologies is low.
      The probability of ophthalmic syphilis may be higher, but we lack objective
      measures for that diagnosis. 

PMID- 25970317
TI  - Identification of post-transcriptional regulatory networks during myeloblast-to
      monocyte differentiation transition.
AB  - Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their
      differentiation block and lead to the transition from myeloblasts to monocytes.
      To identify microRNA-mRNA networks relevant for myeloid differentiation, we
      profiled the expression of mRNAs and microRNAs associated to the low- and high
      density ribosomal fractions in leukemic cells and in their differentiated
      monocytic counterpart. Intersection between mRNAs shifted across the fractions
      after treatment with putative target genes of modulated microRNAs showed a series
      of molecular networks relevant for the monocyte cell fate determination, as for
      example the post-transcriptional regulation of the Polo-like kinase 1 (PLK1) by
      miR-22-3p and let-7e-5p. 

PMID- 25970318
TI  - Variables affecting tooth survival and changes in probing depth: a long-term
      follow-up of periodontitis patients.
AB  - AIM: To retrospectively assess tooth-survival rate and its association with
      patient and oral variables in periodontal office patients, followed up to 18
      years. MATERIAL AND METHODS: Patients in a private periodontal office whose files
      included initial examination (T0 ), reevaluation (TRe ) and >= 10 years after T0
      (TF ) chartings, and received periodontal therapy and supportive periodontal
      therapy (SPT) after TRe were included. General health, plaque scores (PI),
      probing depth (PPD), bleeding on probing (BOP) at six points/tooth, tooth
      extractions, and SPT visits were extracted from patient files at T0 , TRe , and
      TF . Descriptive statistics and Cox regression analysis were performed. RESULTS:
      Fifty patients (mean 26 +/- 4 teeth/patient, 1301 teeth) fulfilled inclusion
      criteria. About 20 and 129 teeth respectively were extracted before/after TRe ,
      96 of them for periodontal causes. PPD>7 mm at TRe (HR = 17.7, 95%CI 8.6, 36.6),
      age above 60 years (HR = 3.3, 95%CI 1.5, 7.2), multi-rooted teeth (HR = 1.9,
      95%CI 1.2, 3.1) and SPT<3 times/year (HR = 1.8, 95%CI 1.1, 2.9), were the best
      prognostic factors for tooth loss during follow-up. (p < 0.05, Cox regression
      analysis). A continuous, statistically significant reduction was observed in mean
      PPD among teeth that survived follow-up [4.3 +/- 1.8 mm, 3.5 +/- 1.4 mm, 3.2 +/-
      1.3 mm, at T0 , TRe , TF , respectively. (p < 0.001, Repeated-measures test)].
      CONCLUSION: Regular SPT was associated with low tooth-loss rates and continuous
      reductions in probing depth. PPD after initial therapy, age above 60, multi
      rooted teeth and infrequent SPT were strong negative prognostic factors for long
      term tooth survival among periodontal patients.

PMID- 25970321
TI  - Structural Effect on Electrochemical Performance of Ordered Porous Carbon
      Electrodes for Na-Ion Batteries.
AB  - Ordered meso- or macro-porous carbons (OMCs) were applied as anodes in Na ion
      battery (NIB) systems. Three different block copolymers (BCPs) enabled us to
      control the pore sizes (6, 33, and 60 nm) while maintaining the same 2-D
      hexagonal structure. To exclude other effects, the factors including precursors,
      particle sizes, and degrees of graphitization were controlled. The structures of
      OMCs were characterized by nitrogen physisorption, Raman spectroscopy, X-ray
      analyses (XRD and SAXS), and microscopies (TEM and SEM). With a galvanostatic
      charge/discharge, we confirmed that OMC electrode with medium pore size (OMC-33)
      exhibited a higher reversible capacity of 134 mA h g(-1) (at 20th cycle) and
      faster rate capability (61% retention, current densities from 50 to 5000 mA g(
      1)) than those of OMC-6, and OMC-60 electrodes. The high performance of OMC-33 is
      attributed to the combined effects of pore size and wall thickness which was
      supported by charge/discharge and electrochemical impedance spectroscopy (EIS)
      analyses. 

PMID- 25970320
TI  - Neuroimaging-based biomarker discovery and validation.

PMID- 25970322
TI  - Promoting Reductive Tandem Reactions of Nitrostyrenes with Mo(CO)6 and a
      Palladium Catalyst To Produce 3H-Indoles.
AB  - The combination of Mo(CO)6 and 10 mol % of palladium acetate catalyzes the
      transformation of 2-nitroarenes to 3H-indoles through a tandem cyclization-[1,2]
      shift reaction of in situ generated nitrosoarenes. Mo(CO)6 appears to have dual
      roles in this transformation: generate CO and promote C-N bond formation to
      increase the yield of the N-heterocycle product. 

PMID- 25970319
TI  - Induction of thermal and mechanical hypersensitivity by parathyroid hormone
      related peptide through upregulation of TRPV1 function and trafficking.
AB  - The neurobiological mechanisms underlying chronic pain associated with cancers
      are not well understood. It has been hypothesized that factors specifically
      elevated in the tumor microenvironment sensitize adjacent nociceptive afferents.
      We show that parathyroid hormone-related peptide (PTHrP), which is found at
      elevated levels in the tumor microenvironment of advanced breast and prostate
      cancers, is a critical modulator of sensory neurons. Intraplantar injection of
      PTHrP led to the development of thermal and mechanical hypersensitivity in both
      male and female mice, which were absent in mice lacking functional transient
      receptor potential vanilloid-1 (TRPV1). The PTHrP treatment of cultured mouse
      sensory neurons enhanced action potential firing, and increased TRPV1 activation,
      which was dependent on protein kinase C (PKC) activity. Parathyroid hormone
      related peptide induced robust potentiation of TRPV1 activation and enhancement
      of neuronal firing at mild acidic pH that is relevant to acidic tumor
      microenvironment. We also observed an increase in plasma membrane TRPV1 protein
      levels after exposure to PTHrP, leading to upregulation in the proportion of
      TRPV1-responsive neurons, which was dependent on the activity of PKC and Src
      kinases. Furthermore, co-injection of PKC or Src inhibitors attenuated PTHrP
      induced thermal but not mechanical hypersensitivity. Altogether, our results
      suggest that PTHrP and mild acidic conditions could induce constitutive
      pathological activation of sensory neurons through upregulation of TRPV1 function
      and trafficking, which could serve as a mechanism for peripheral sensitization of
      nociceptive afferents in the tumor microenvironment. 

PMID- 25970323
TI  - Catalyst-controlled dioxygenation of olefins: an approach to peroxides, alcohols,
      and ketones.
AB  - An efficient catalytic approach for the synthesis of substituted peroxides,
      alcohols, and ketones through a catalyst-controlled highly selective
      dioxygenation of olefins has been demonstrated. The reported methods are mild and
      practical, can be switched by the selection of different catalytic systems, and
      employ peroxide as an oxidant and a reagent at room temperature. 

PMID- 25970324
TI  - Discovery of N-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4
      methylthiophen-2-yl)phthalazin-1-amine (AMG 900), a highly selective, orally
      bioavailable inhibitor of aurora kinases with activity against multidrug
      resistant cancer cell lines.
AB  - Efforts to improve upon the physical properties and metabolic stability of Aurora
      kinase inhibitor 14a revealed that potency against multidrug-resistant cell lines
      was compromised by increased polarity. Despite its high in vitro metabolic
      intrinsic clearance, 23r (AMG 900) showed acceptable pharmacokinetic properties
      and robust pharmacodynamic activity. Projecting from in vitro data to in vivo
      target coverage was not practical due to disjunctions between enzyme and cell
      data, complex and apparently contradictory indicators of binding kinetics, and
      unmeasurable free fraction in plasma. In contrast, it was straightforward to
      relate pharmacokinetics to pharmacodynamics and efficacy by following the time
      above a threshold concentration. On the basis of its oral route of
      administration, a selectivity profile that favors Aurora-driven pharmacology and
      its activity against multidrug-resistant cell lines, 23r was identified as a
      potential best-in-class Aurora kinase inhibitor. In phase 1 dose expansion
      studies with G-CSF support, 23r has shown promising single agent activity. 

PMID- 25970325
TI  - Loneliness and Negative Affective Conditions in Adults: Is There Any Room for
      Hope in Predicting Anxiety and Depressive Symptoms?
AB  - This study examined the role of hope in understanding the link between loneliness
      and negative affective conditions (viz., anxiety and depressive symptoms) in a
      sample of 318 adults. As expected, loneliness was found to be a significant
      predictor of both anxiety and depressive symptoms. Noteworthy, hope was found to
      significantly augment the prediction of depressive symptoms, even after
      accounting for loneliness. Furthermore, we found evidence for a significant
      Loneliness * Hope interaction effect in predicting anxiety. A plot of the
      interaction confirmed that the association between loneliness and anxiety was
      weaker among high, compared to low, hope adults. Some implications of the present
      findings are discussed.

PMID- 25970326
TI  - Association of platelet activation markers with cancer-associated venous
      thromboembolism.
AB  - Venous thromboembolism (VTE) is a frequent complication in cancer patients.
      Platelet activation is thought to be involved in cancer-associated VTE. Here, we
      determined the association between evolving markers of platelet activation
      (soluble P-selectin [sP-selectin], soluble CD40 ligand [sCD40L], thrombospondin-1
      [TSP-1] and platelet factor-4 [PF-4]) and the development of cancer-associated
      VTE. A nested matched case-control study was applied within a cohort of 1779
      patients with different types of cancer that had been included in the Vienna
      Cancer and Thrombosis Study (CATS), a prospective, observational study on
      patients with newly diagnosed or progressive cancer after remission. Primary
      endpoint is symptomatic VTE during a maximum follow-up of 2 years. Cases
      (patients who developed VTE during follow-up) were matched in a 1:2 ratio to
      controls without VTE during follow-up with respect to tumor type, stage and time
      of observation in the study. In total, 131 VTE cases were compared to 262
      controls. In logistic regression analysis, only sP-selectin was associated with
      risk of VTE. The odds ratios (OR) per double increase of sP-selectin, sCD40L, TSP
      1 and PF-4 were 1.66 (95% confidence interval: 1.17-2.35, p = 0.005), 1.04 (0.89
      1.21, p = 0.635), 1.09 (0.90-1.32, p = 0.360) and 1.03 (0.87-1.21, p = 0.737),
      respectively. In conclusion, sP-selectin, but not sCD40L, TSP-1 or PF-4 were
      associated with risk of VTE in cancer patients in this nested case-control study.

PMID- 25970327
TI  - Crossmodal integration improves sensory detection thresholds in the ferret.
AB  - During the last two decades ferrets (Mustela putorius) have been established as a
      highly efficient animal model in different fields in neuroscience. Here we asked
      whether ferrets integrate sensory information according to the same principles
      established for other species. Since only few methods and protocols are available
      for behaving ferrets we developed a head-free, body-restrained approach allowing
      a standardized stimulation position and the utilization of the ferret's natural
      response behavior. We established a behavioral paradigm to test audiovisual
      integration in the ferret. Animals had to detect a brief auditory and/or visual
      stimulus presented either left or right from their midline. We first determined
      detection thresholds for auditory amplitude and visual contrast. In a second
      step, we combined both modalities and compared psychometric fits and the reaction
      times between all conditions. We employed Maximum Likelihood Estimation (MLE) to
      model bimodal psychometric curves and to investigate whether ferrets integrate
      modalities in an optimal manner. Furthermore, to test for a redundant signal
      effect we pooled the reaction times of all animals to calculate a race model. We
      observed that bimodal detection thresholds were reduced and reaction times were
      faster in the bimodal compared to unimodal conditions. The race model and MLE
      modeling showed that ferrets integrate modalities in a statistically optimal
      fashion. Taken together, the data indicate that principles of multisensory
      integration previously demonstrated in other species also apply to crossmodal
      processing in the ferret. 

PMID- 25970328
TI  - The Assembly of EDC4 and Dcp1a into Processing Bodies Is Critical for the
      Translational Regulation of IL-6.
AB  - Macrophages play critical roles in the onset of various diseases and in
      maintaining homeostasis. There are several functional subsets, of which M1 and M2
      macrophages are of particular interest because they are differentially involved
      in inflammation and its resolution. Here, we investigated the differences in
      regulatory mechanisms between M1- and M2-polarized macrophages by examining mRNA
      metabolic machineries such as stress granules (SGs) and processing bodies (P
      bodies). Human monocytic leukemia THP-1 cells cultured under M1-polarizing
      conditions (M1-THPs) had less ability to assemble oxidative-stress-induced SGs
      than those cultured under M2-polarizing conditions (M2-THPs). In contrast, P-body
      assembly in response to oxidative stress or TLR4 stimulation was increased in M1
      THPs as compared to M2-THPs. These results suggest that mRNA metabolism is
      controlled differently in M1-THPs and M2-THPs. Interestingly, knocking down EDC4
      or Dcp1a, which are components of P-bodies, severely reduced the production of IL
      6, but not TNF-alpha in M1-THPs without decreasing the amount of IL-6 mRNA. This
      is the first report to demonstrate that the assembly of EDC4 and Dcp1a into P
      bodies is critical in the posttranscriptional regulation of IL-6. Thus, improving
      our understanding of the mechanisms governing mRNA metabolism by examining
      macrophage subtypes may lead to new therapeutic targets. 

PMID- 25970329
TI  - Mapping a Large Number of QTL for Durable Resistance to Stripe Rust in Winter
      Wheat Druchamp Using SSR and SNP Markers.
AB  - Winter wheat Druchamp has both high-temperature adult-plant (HTAP) resistance and
      all-stage resistance to stripe rust caused by Puccinia striiformis f. sp. tritici
      (Pst). The HTAP resistance in Druchamp is durable as the variety has been
      resistant in adult-plant stage since it was introduced from France to the United
      States in late 1940s. To map the quantitative trait loci (QTL) for stripe rust
      resistance, an F8 recombinant inbred line (RIL) population from cross Druchamp *
      Michigan Amber was phenotyped for stripe rust response in multiple years in
      fields under natural infection and with selected Pst races under controlled
      greenhouse conditions, and genotyped with simple sequence repeat (SSR) and single
      nucleotide polymorphism (SNP) markers. Composite interval mapping (CIM)
      identified eight HTAP resistance QTL and three all-stage resistance QTL. Among
      the eight HTAP resistance QTL, QYrdr.wgp-1BL.2 (explaining 2.36-31.04%
      variation), QYrdr.wgp-2BL (2.81-15.65%), QYrdr.wgp-5AL (2.27-17.22%) and
      QYrdr.wgp-5BL.2 (2.42-15.13%) were significant in all tests; and QYrdr.wgp-1BL.1
      (1.94-10.19%), QYrdr.wgp-1DS (2.04-27.24%), QYrdr.wgp-3AL (1.78-13.85%) and
      QYrdr.wgp-6BL.2 (1.69-33.71%) were significant in some of the tests. The three
      all-stage resistance QTL, QYrdr.wgp-5BL.1 (5.47-36.04%), QYrdr.wgp-5DL (9.27
      11.94%) and QYrdr.wgp-6BL.1 (13.07-20.36%), were detected based on reactions in
      the seedlings tested with certain Pst races. Among the eleven QTL detected in
      Druchamp, at least three (QYrdr.wgp-5DL for race-specific all-stage resistance
      and QYrdr.wgp-3AL and QYrdr.wgp-6BL.2 for race non-specific HTAP resistance) are
      new. All these QTL, especially those for durable HTAP resistance, and their
      closely linked molecular markers could be useful for developing wheat cultivars
      with durable resistance to stripe rust. 

PMID- 25970331
TI  - Correction: Comprehensive profiling of plasma fatty acid concentrations in young
      healthy Canadian adults.

PMID- 25970330
TI  - A Drosophila model identifies a critical role for zinc in mineralization for
      kidney stone disease.
AB  - Ectopic calcification is a driving force for a variety of diseases, including
      kidney stones and atherosclerosis, but initiating factors remain largely unknown.
      Given its importance in seemingly divergent disease processes, identifying
      fundamental principal actors for ectopic calcification may have broad
      translational significance. Here we establish a Drosophila melanogaster model for
      ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads
      to kidney stones in humans and dogs. Micro X-ray absorption near edge
      spectroscopy (MUXANES) synchrotron analyses revealed high enrichment of zinc in
      the Drosophila equivalent of kidney stones, which was also observed in human
      kidney stones and Randall's plaques (early calcifications seen in human kidneys
      thought to be the precursor for renal stones). To further test the role of zinc
      in driving mineralization, we inhibited zinc transporter genes in the ZnT family
      and observed suppression of Drosophila stone formation. Taken together, genetic,
      dietary, and pharmacologic interventions to lower zinc confirm a critical role
      for zinc in driving the process of heterogeneous nucleation that eventually leads
      to stone formation. Our findings open a novel perspective on the etiology of
      urinary stones and related diseases, which may lead to the identification of new
      preventive and therapeutic approaches. 

PMID- 25970332
TI  - Hepatocyte-Specific Depletion of UBXD8 Induces Periportal Steatosis in Mice Fed a
      High-Fat Diet.
AB  - We showed previously that UBXD8 plays a key role in proteasomal degradation of
      lipidated ApoB in hepatocarcinoma cell lines. In the present study, we aimed to
      investigate the functions of UBXD8 in liver in vivo. For this purpose, hepatocyte
      specific UBXD8 knockout (UBXD8-LKO) mice were generated. They were fed with a
      normal or high-fat diet, and the phenotypes were compared with those of
      littermate control mice. Hepatocytes obtained from UBXD8-LKO and control mice
      were analyzed in culture. After 26 wk of a high-fat diet, UBXD8-LKO mice
      exhibited macrovesicular steatosis in the periportal area and microvesicular
      steatosis in the perivenular area, whereas control mice exhibited steatosis only
      in the perivenular area. Furthermore, UBXD8-LKO mice on a high-fat diet had
      significantly lower concentrations of serum triglyceride and VLDL than control
      mice. A Triton WR-1339 injection study revealed that VLDL secretion from
      hepatocytes was reduced in UBXD8-LKO mice. The decrease of ApoB secretion upon
      UBXD8 depletion was recapitulated in cultured primary hepatocytes. Accumulation
      of lipidated ApoB in lipid droplets was observed only in UBXD8-null hepatocytes.
      The results showed that depletion of UBXD8 in hepatocytes suppresses VLDL
      secretion, and could lead to periportal steatosis when mice are fed a high-fat
      diet. This is the first demonstration that an abnormality in the intracellular
      ApoB degradation mechanism can cause steatosis, and provides a useful model for
      periportal steatosis, which occurs in several human diseases. 

PMID- 25970333
TI  - House Fly (Musca domestica L.) Attraction to Insect Honeydew.
AB  - House flies are of major concern as vectors of food-borne pathogens to food
      crops. House flies are common pests on cattle feedlots and dairies, where they
      develop in and feed on animal waste. By contacting animal waste, house flies can
      acquire human pathogenic bacteria such as Escherichia coli and Salmonella spp.,
      in addition to other bacteria, viruses, or parasites that may infect humans and
      animals. The subsequent dispersal of house flies from animal facilities to nearby
      agricultural fields containing food crops may lead to pre-harvest food
      contamination with these pathogens. We hypothesized that odors from honeydew, the
      sugary excreta produced by sucking insects feeding on crops, or molds and fungi
      growing on honeydew, may attract house flies, thereby increasing the risk of food
      crop contamination. House fly attraction to honeydew-contaminated plant material
      was evaluated using a laboratory bioassay. House flies were attracted to the
      following plant-pest-honeydew combinations: citrus mealybug on squash fruit, pea
      aphid on faba bean plants, whitefly on navel orange and grapefruit leaves, and
      combined citrus mealybug and cottony cushion scale on mandarin orange leaves.
      House flies were not attracted to field-collected samples of lerp psyllids on
      eucalyptus plants or aphids on crepe myrtle leaves. Fungi associated with field
      collected honeydews were isolated and identified for further study as possible
      emitters of volatiles attractive to house flies. Two fungal species,
      Aureobasidium pullulans and Cladosporium cladosporioides, were repeatedly
      isolated from field-collected honeydew samples. Both fungal species were grown in
      potato dextrose enrichment broth and house fly attraction to volatiles from these
      fungal cultures was evaluated. House flies were attracted to odors from A.
      pullulans cultures but not to those of C. cladosporioides. Identification of
      specific honeydew odors that are attractive to house flies could be valuable for
      the development of improved house fly baits for management of this pest species. 

PMID- 25970335
TI  - Protein structure and evolution: are they constrained globally by a principle
      derived from information theory?
AB  - That the physicochemical properties of amino acids constrain the structure,
      function and evolution of proteins is not in doubt. However, principles derived
      from information theory may also set bounds on the structure (and thus also the
      evolution) of proteins. Here we analyze the global properties of the full set of
      proteins in release 13-11 of the SwissProt database, showing by experimental test
      of predictions from information theory that their collective structure exhibits
      properties that are consistent with their being guided by a conservation
      principle. This principle (Conservation of Information) defines the global
      properties of systems composed of discrete components each of which is in turn
      assembled from discrete smaller pieces. In the system of proteins, each protein
      is a component, and each protein is assembled from amino acids. Central to this
      principle is the inter-relationship of the unique amino acid count and total
      length of a protein and its implications for both average protein length and
      occurrence of proteins with specific unique amino acid counts. The unique amino
      acid count is simply the number of distinct amino acids (including those that are
      post-translationally modified) that occur in a protein, and is independent of the
      number of times that the particular amino acid occurs in the sequence.
      Conservation of Information does not operate at the local level (it is
      independent of the physicochemical properties of the amino acids) where the
      influences of natural selection are manifest in the variety of protein structure
      and function that is well understood. Rather, this analysis implies that
      Conservation of Information would define the global bounds within which the whole
      system of proteins is constrained; thus it appears to be acting to constrain
      evolution at a level different from natural selection, a conclusion that appears
      counter-intuitive but is supported by the studies described herein. 

PMID- 25970334
TI  - Effects of valproic acid and dexamethasone administration on early bio-markers
      and gene expression profile in acute kidney ischemia-reperfusion injury in the
      rat.
AB  - Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high
      mortality and morbidity. The objective of this investigation was to ameliorate
      kidney IR injury and identify novel biomarkers for kidney injury and repair.
      Under general anesthesia, left renal ischemia was induced in Wister rats by
      occluding renal artery for 45 minutes, followed by reperfusion and right
      nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group) received
      Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (saline)
      intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma
      creatinine (mg/dL) at 24 h was reduced (P<0.05) in VPA (2.7+/-1.8) and Dex (2.3+/
      1.2) compared to Vehicle (3.8+/-0.5) group. At 3 h, urine albumin (mg/mL) was
      higher in Vehicle (1.47+/-0.10), VPA (0.84+/-0.62) and Dex (1.04+/-0.73) compared
      to naive (uninjured/untreated control) (0.14+/-0.26) group. At 24 h post-IR urine
      lipocalin-2 (MUg/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (9.61
      11.36) compared to naive group (0.67+/-0.29); also, kidney injury molecule-1 (KIM
      1; ng/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (13.7-18.7) compared
      to naive group (1.7+/-1.9). Histopathology demonstrated reduced (P<0.05) ischemic
      injury in the renal cortex in VPA (Grade 1.6+/-1.5) compared to Vehicle (Grade
      2.9+/-1.1). Inflammatory cytokines IL1beta and IL6 were downregulated and anti
      apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA
      microarray demonstrated reduced injury, stress, and apoptosis related gene
      expression in the VPA administered rats. VPA appears to ameliorate kidney IR
      injury via reduced inflammatory cytokine, apoptosis/stress related gene
      expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to
      be promising early urine biomarkers for the diagnosis of AKI. 

PMID- 25970336
TI  - Vitamin D deficiency at melanoma diagnosis is associated with higher Breslow
      thickness.
AB  - BACKGROUND: Epidemiological evidence shows that people with thicker, or higher
      stage, melanomas have lower vitamin D status compared to those with thinner
      tumours. Evidence from experimental studies is inconsistent, but some suggest
      that administration of vitamin D metabolites can decrease tumour aggressiveness.
      OBJECTIVES: Determine the relationship between vitamin D status at diagnosis and
      melanoma thickness (as an indicator of prognosis), in a subtropical setting with
      high melanoma incidence. METHODS: We recruited 100 melanoma patients in Brisbane,
      Australia within days of their diagnosis. Data on factors previously associated
      with melanoma risk or prognosis were collected by questionnaire and physical
      examination. Serum for 25-hydroxyvitamin D3 [25(OH)D] levels was collected prior
      to wider excision biopsy; histological indicators of prognosis were obtained from
      pathology reports. We used multivariable logistic regression models to analyse
      the association between Breslow thickness (>=0.75 mm compared to <0.75 mm), Clark
      level (2-5 compared to 1) and presence of mitoses, and vitamin D status. RESULTS:
      Serum 25(OH)D <50 nmol/L (versus >=50 nmol/L) was associated with a nearly four
      fold increase in risk of having a thicker tumour (Adjusted OR = 3.82, 95% CI:
      1.03, 14.14; p = 0.04, adjusted for age, sex, skin phototype, body mass index and
      season at diagnosis). There was no significant association with Clark level or
      presence of mitosis. Serum 25(OH)D levels in the highest quartile (>=69.8 nmol/L)
      were not associated with a more favourable prognosis. CONCLUSIONS: Vitamin D
      deficiency at the time of melanoma diagnosis is associated with thicker tumours
      that are likely to have a poorer prognosis. Ensuring vitamin D levels of 50
      nmol/L or higher in this population could potentially result in 18% of melanomas
      having Breslow thickness of <0.75 mm rather than >=0.75 mm.

PMID- 25970338
TI  - Systems mapping for hematopoietic progenitor cell heterogeneity.
AB  - Cells with the same genotype growing under the same conditions can show different
      phenotypes, which is known as "population heterogeneity". The heterogeneity of
      hematopoietic progenitor cells has an effect on their differentiation potential
      and lineage choices. However, the genetic mechanisms governing population
      heterogeneity remain unclear. Here, we present a statistical model for mapping
      the quantitative trait locus (QTL) that affects hematopoietic cell heterogeneity.
      This strategy, termed systems mapping, integrates a system of differential
      equations into the framework for systems mapping, allowing hypotheses regarding
      the interplay between genetic actions and cell heterogeneity to be tested. A
      simulation approach based on cell heterogeneity dynamics has been designed to
      test the statistical properties of the model. This model not only considers the
      traditional QTLs, but also indicates the methylated QTLs that can illustrate non
      genetic individual differences. It has significant implications for probing the
      molecular, genetic and epigenetic mechanisms of hematopoietic progenitor cell
      heterogeneity. 

PMID- 25970339
TI  - The effects of bispectral index monitoring on hemodynamics and recovery profile
      in developmentally delayed pediatric patients undergoing dental surgery.
AB  - BACKGROUND: General anesthesia is often preferred for dental surgery or
      rehabilitation in developmentally delayed pediatric patients. Bispectral index
      monitoring is used to monitor the depth of anesthesia and to ensure early
      recovery. However, studies on the topic in developmentally delayed pediatric
      patients are limited. AIM: To evaluate the effects of Bispectral Index Scale
      (BIS) on hemodynamics and recovery profile in developmentally delayed pediatric
      patients undergoing dental surgery. METHODS: Forty children between the ages of 6
      16 years were studied in this prospective and randomized study. The children were
      randomized into two groups. In Group 1 (n = 20), general anesthesia was
      maintained with 1-2 minimum alveolar concentration (MAC) of sevoflurane in oxygen
      by standard practice. In Group 2 (n = 20), the depth of anesthesia was monitored
      by BIS. BIS values were continuously recorded from awake status to tracheal
      extubation. The duration of the surgical procedure, anesthesia, postanesthesia
      care unit (PACU) stay was noted. To evaluate recovery profile, time to
      spontaneous ventilation, extubation, open eyes, and PACU discharge were also
      noted. RESULTS: There were significant differences between recovery times and Non
      communicating Children's Pain Checklist - Postoperative Version (NCCPC-PV) scores
      of two groups. Time to spontaneous ventilation [Difference in means (95% CI);
      3.17 (1.79-4.54) P < 0.001], extubation [Difference in means (95% CI); 3.13 (1.66
      4.60) P < 0.001], open eyes [Difference in means (95% CI); 3.97 (2.34-5.59) P <
      0.001], and PACU stay time [Difference in means (95% CI); 23.55 (18.08-29.01) P <
      0.001] were significantly shorter in Group 2. CONCLUSION: In conclusion, results
      suggest that routine BIS monitoring may be beneficial due to its favorable
      effects on the recovery profile in developmentally delayed pediatric patients.

PMID- 25970337
TI  - Combination Therapies for Traumatic Brain Injury: Retrospective Considerations.
AB  - Patients enrolled in clinical trials for traumatic brain injury (TBI) may present
      with heterogeneous features over a range of injury severity, such as diffuse
      axonal injury, ischemia, edema, hemorrhage, oxidative damage, mitochondrial and
      metabolic dysfunction, excitotoxicity, inflammation, and other pathophysiological
      processes. To determine whether combination therapies might be more effective
      than monotherapy at attenuating moderate TBI or promoting recovery, the National
      Institutes of Health funded six preclinical studies in adult and immature male
      rats to evaluate promising acute treatments alone and in combination. Each of the
      studies had a solid rationale for its approach based on previous research, but
      only one reported significant improvements in long-term outcomes across a battery
      of behavioral tests. Four studies had equivocal results because of a lack of
      sensitivity of the outcome assessments. One study demonstrated worse results with
      the combination in comparison with monotherapies. While specific research
      findings are reported elsewhere, this article provides an overview of the study
      designs, insights, and recommendations for future research aimed at therapy
      development for TBI. 

PMID- 25970340
TI  - Long-Term Conditioning to Elevated pCO2 and Warming Influences the Fatty and
      Amino Acid Composition of the Diatom Cylindrotheca fusiformis.
AB  - The unabated rise in anthropogenic CO2 emissions is predicted to strongly
      influence the ocean's environment, increasing the mean sea-surface temperature by
      4 degrees C and causing a pH decline of 0.3 units by the year 2100. These changes
      are likely to affect the nutritional value of marine food sources since
      temperature and CO2 can influence the fatty (FA) and amino acid (AA) composition
      of marine primary producers. Here, essential amino (EA) and polyunsaturated fatty
      (PUFA) acids are of particular importance due to their nutritional value to
      higher trophic levels. In order to determine the interactive effects of CO2 and
      temperature on the nutritional quality of a primary producer, we analyzed the
      relative PUFA and EA composition of the diatom Cylindrotheca fusiformis cultured
      under a factorial matrix of 2 temperatures (14 and 19 degrees C) and 3 partial
      pressures of CO2 (180, 380, 750 MUatm) for >250 generations. Our results show a
      decay of ~3% and ~6% in PUFA and EA content in algae kept at a pCO2 of 750 MUatm
      (high) compared to the 380 MUatm (intermediate) CO2 treatments at 14 degrees C.
      Cultures kept at 19 degrees C displayed a ~3% lower PUFA content under high
      compared to intermediate pCO2, while EA did not show differences between
      treatments. Algae grown at a pCO2 of 180 MUatm (low) had a lower PUFA and AA
      content in relation to those at intermediate and high CO2 levels at 14 degrees C,
      but there were no differences in EA at 19 degrees C for any CO2 treatment. This
      study is the first to report adverse effects of warming and acidification on the
      EA of a primary producer, and corroborates previous observations of negative
      effects of these stressors on PUFA. Considering that only ~20% of essential
      biomolecules such as PUFA (and possibly EA) are incorporated into new biomass at
      the next trophic level, the potential impacts of adverse effects of ocean warming
      and acidification at the base of the food web may be amplified towards higher
      trophic levels, which rely on them as source of essential biomolecules. 

PMID- 25970341
TI  - Binding Affinity, Specificity and Comparative Biodistribution of the Parental
      Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version
      Rebmab200.
AB  - The aim of this preclinical study was to evaluate the characteristics of the
      monoclonal antibody Rebmab200, which is a humanized version of the ovarian
      specific murine antibody MX35. This investigation contributes to the foundation
      for future clinical alpha-radioimmunotherapy of minimal residual ovarian cancer
      with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated,
      as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly
      compared with its murine counterpart MX35 in terms of its in-vitro capacity for
      binding the immobilized NaPi2B epitope and live cells; we also assessed its
      biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen
      and cell binding were similar between Rebmab200 and murine MX35, as was
      biodistribution, including normal tissue uptake and in-vivo tumor binding. We
      also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission
      computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice.
      Taken together, our data support the further development of Rebmab200 for
      radioimmunotherapy and diagnostics. 

PMID- 25970342
TI  - Generation of a Functionally Distinct Rhizopus oryzae Lipase through Protein
      Folding Memory.
AB  - Rhizopus oryzae lipase (ROL) has a propeptide at its N-terminus that functions as
      an intramolecular chaperone and facilitates the folding of mature ROL (mROL). In
      this study, we successfully generated a functionally distinct imprinted mROL
      (mROLimp) through protein folding memory using a mutated propeptide. The mutated
      propeptide left its structural memory on mROL and produced mROLimp that exhibited
      different substrate specificities compared with mROLWT (prepared from the wild
      type propeptide), although the amino acid sequences of both mROLs were the same.
      mROLimp showed a preference for substrates with medium chain-length acyl groups
      and, noticeably, recognized a peptidase-specific substrate. In addition, ROLimp
      was more stable than mROLWT. These results strongly suggest that proteins with
      identical amino acid sequences can fold into different conformations and that
      mutations in intramolecular chaperones can dynamically induce changes in
      enzymatic activity. 

PMID- 25970344
TI  - A novel microbial source tracking microarray for pathogen detection and fecal
      source identification in environmental systems.
AB  - Pathogen detection and the identification of fecal contamination sources are
      challenging in environmental waters. Factors including pathogen diversity and
      ubiquity of fecal indicator bacteria hamper risk assessment and remediation of
      contamination sources. A custom microarray targeting pathogens (viruses,
      bacteria, protozoa), microbial source tracking (MST) markers, and antibiotic
      resistance genes was tested against DNA obtained from whole genome amplification
      (WGA) of RNA and DNA from sewage and animal (avian, cattle, poultry, and swine)
      feces. Perfect and mismatch probes established the specificity of the microarray
      in sewage, and fluorescence decrease of positive probes over a 1:10 dilution
      series demonstrated semiquantitative measurement. Pathogens, including norovirus,
      Campylobacter fetus, Helicobacter pylori, Salmonella enterica, and Giardia
      lamblia were detected in sewage, as well as MST markers and resistance genes to
      aminoglycosides, beta-lactams, and tetracycline. Sensitivity (percentage true
      positives) of MST results in sewage and animal waste samples (21-33%) was lower
      than specificity (83-90%, percentage of true negatives). Next generation DNA
      sequencing revealed two dominant bacterial families that were common to all
      sample types: Ruminococcaceae and Lachnospiraceae. Five dominant phyla and 15
      dominant families comprised 97% and 74%, respectively, of sequences from all
      fecal sources. Phyla and families not represented on the microarray are possible
      candidates for inclusion in subsequent array designs.

PMID- 25970343
TI  - Calprotectin and platelet aggregation in patients with stable coronary artery
      disease.
AB  - BACKGROUND: Recent studies suggest that the inflammation-associated protein
      calprotectin may be implicated in the pathogenesis of coronary artery disease
      (CAD). However, the impact of calprotectin levels on platelet aggregation in CAD
      patients has never been investigated. OBJECTIVES: We investigated the association
      between calprotectin levels and platelet aggregation in stable, high-risk CAD
      patients receiving aspirin as mono antiplatelet therapy. Furthermore, we aimed to
      investigate independent clinical and laboratory determinants of calprotectin
      levels. METHODS: We performed a cross-sectional study including 581 stable, high
      risk CAD patients. All patients received 75 mg aspirin daily as mono antiplatelet
      therapy. Platelet aggregation was assessed by 1) impedance aggregometry
      (Multiplate Analyzer) using arachidonic acid (AA) and collagen as agonists and by
      2) the VerifyNow Aspirin Assay. Low-grade inflammation was evaluated by
      calprotectin, high-sensitive C-reactive-protein (hs-CRP) and interleukin-6.
      Platelet activation was assessed by soluble P-selectin, and cyclooxygenase-1
      inhibition was evaluated by serum thromboxane B2, both measured by ELISA.
      RESULTS: Calprotectin levels correlated positively with platelet aggregation
      according to Multiplate Analyzer (r=0.12, p=0.01). Additionally, calprotectin was
      positively associated with leukocytes (r=0.33, p<0.0001), hs-CRP (r=0.31,
      p<0.0001), interleukin-6 (r=0.28, p<0.0001), soluble P-selectin (r=0.10, p=0.02)
      and serum thromboxane B2 (r=0.10, p=0.02). Type 2 diabetes mellitus was an
      independent predictor of increased calprotectin levels (p=0.004), and trends were
      seen for body mass index (p=0.06) and smoking (p=0.07). Compliance with aspirin
      was confirmed by low serum thromboxane B2 levels in all patients (median
      [25%;75%]: 1.07 [0.52;1.87] ng/mL). CONCLUSION: Calprotectin levels correlated
      positively, though weakly, with platelet aggregation and activation as well as
      serum thromboxane B2 in high-risk, stable CAD patients treated with aspirin.

PMID- 25970346
TI  - Preschoolers' understanding of merit in two Asian societies.
AB  - Recent research in moral psychology have suggested that children make judgments
      about distributive justice early on in development, and in particular they appear
      to be able to use merit when distributing the benefits of a collective action.
      This prediction has recently been validated in various western cultures but it is
      unknown whether it also applies to more collectivistic cultures, in which the
      group might be favoured over the individual, and need over merit. Here, we
      investigate merit-based distributions among 81 children belonging to two Asian
      societies, China and Japan (mean age = 5.0 years). In line with the idea that
      children's moral psychology develops early, we found that Chinese and Japanese
      children are able to use merit to distribute the benefits of a collective action.

PMID- 25970345
TI  - Differential Effects of Tra2beta Isoforms on HIV-1 RNA Processing and Expression.
AB  - Balanced processing of HIV-1 RNA is critical to virus replication and is
      regulated by host factors. In this report, we demonstrate that overexpression of
      either Tra2alpha or Tra2beta results in a marked reduction in HIV-1 Gag/Env
      expression, an effect associated with changes in HIV-1 RNA accumulation, altered
      viral splice site usage, and a block to export of HIV-1 genomic RNA. A natural
      isoform of Tra2beta (Tra2beta3), lacking the N-terminal RS domain, also
      suppressed HIV-1 expression but had different effects on viral RNA processing.
      The functional differences between the Tra2beta isoforms were also observed in
      the context of another RNA substrate indicating that these factors have distinct
      functions within the cell. Finally, we demonstrate that Tra2beta depletion
      results in a selective reduction in HIV-1 Env expression as well as an increase
      in multiply spliced viral RNA. Together, the findings indicate that
      Tra2alpha/beta can play important roles in regulating HIV-1 RNA metabolism and
      expression.

PMID- 25970347
TI  - Bridging the gap: the role of Physiatrists in caring for adults with cerebral
      palsy.
AB  - PURPOSE: Individuals with cerebral palsy (CP) experience a significant gap in
      care as they move from interdisciplinary pediatric programs to limited or non
      existent care in the adult sector. A lack of knowledgeable adult care providers
      has repeatedly been identified as a challenge in transitioning those with CP from
      pediatric to adult care. The objective of this study was to determine the extent
      to which Physiatrists provide care to adults with CP and to identify barriers to
      their engagement with this population. METHOD: A survey was distributed to
      Physiatrists across Canada. Results were analyzed descriptively using SPSS
      software. RESULTS: Most Physiatrists provide care to very few adults with CP (10
      or less), but over 80% feel that Physiatry is the most appropriate specialty to
      provide disability-related care to adults with CP following their pediatric
      discharge. Among the most frequently identified barriers to caring for this
      population were lack of accessible resources (i.e. social work, funded therapy,
      equipment) and lack of referrals. CONCLUSIONS: Physiatrists are willing and
      appropriate partners in transitioning patients with CP to adult care. Barriers to
      Physiatrists' engagement with this population appear to be amenable to change.
      IMPLICATIONS FOR REHABILITATION: A lack of knowledgeable and interested adult
      practitioners has repeatedly been identified as a challenge in transition
      planning for young adults with cerebral palsy (the vast majority of whom survive
      into adulthood). Physiatrists are ideally suited to manage adults with cerebral
      palsy, yet in this survey-based study, a majority of Canadian Physiatrists report
      caring for less than five adults with cerebral palsy on a regular basis. Barriers
      to further physiatric involvement in this population were reported to include
      lack of accessible resources and lack of referrals.

PMID- 25970348
TI  - Computational modeling of seizure dynamics using coupled neuronal networks:
      factors shaping epileptiform activity.
AB  - Epileptic seizure dynamics span multiple scales in space and time. Understanding
      seizure mechanisms requires identifying the relations between seizure components
      within and across these scales, together with the analysis of their dynamical
      repertoire. Mathematical models have been developed to reproduce seizure dynamics
      across scales ranging from the single neuron to the neural population. In this
      study, we develop a network model of spiking neurons and systematically
      investigate the conditions, under which the network displays the emergent dynamic
      behaviors known from the Epileptor, which is a well-investigated abstract model
      of epileptic neural activity. This approach allows us to study the biophysical
      parameters and variables leading to epileptiform discharges at cellular and
      network levels. Our network model is composed of two neuronal populations,
      characterized by fast excitatory bursting neurons and regular spiking inhibitory
      neurons, embedded in a common extracellular environment represented by a slow
      variable. By systematically analyzing the parameter landscape offered by the
      simulation framework, we reproduce typical sequences of neural activity observed
      during status epilepticus. We find that exogenous fluctuations from extracellular
      environment and electro-tonic couplings play a major role in the progression of
      the seizure, which supports previous studies and further validates our model. We
      also investigate the influence of chemical synaptic coupling in the generation of
      spontaneous seizure-like events. Our results argue towards a temporal shift of
      typical spike waves with fast discharges as synaptic strengths are varied. We
      demonstrate that spike waves, including interictal spikes, are generated
      primarily by inhibitory neurons, whereas fast discharges during the wave part are
      due to excitatory neurons. Simulated traces are compared with in vivo
      experimental data from rodents at different stages of the disorder. We draw the
      conclusion that slow variations of global excitability, due to exogenous
      fluctuations from extracellular environment, and gap junction communication push
      the system into paroxysmal regimes. We discuss potential mechanisms underlying
      such machinery and the relevance of our approach, supporting previous detailed
      modeling studies and reflecting on the limitations of our methodology. 

PMID- 25970349
TI  - A Register-Based Study of Diseases With an Autosomal Recessive Origin in Small
      Children in Denmark According to Maternal Country of Origin.
AB  - BACKGROUND: Compared with children born of Danish mothers, the mortality of
      children, born and living in Denmark, is significantly increased in those with a
      mother from Afghanistan, Iraq, Pakistan, Somalia, and Turkey. Consanguinity has
      been suggested to account for part of this disparity. Since information on
      consanguinity is lacking, this suggestion is difficult to test. With an indirect
      approach, we addressed this question by comparing the risk of diseases with
      autosomal recessive inheritance in children born in Denmark of Danish-born women
      and of women born in these five countries, respectively. METHODS: All children
      born in Denmark (1994-2010) were followed until 5 years of age or end-of-study
      period for the risk of hospitalisation with diseases of autosomal recessive
      aetiology, and therefore considered consanguinity-related. Diagnoses of autosomal
      recessive diseases were identified using two different methods: a literature
      review of consanguinity-associated diseases and a search in the Online Catalogue
      of Human Genes and Genetic Disorders. Risks were also calculated for diseases
      with known non-autosomal recessive aetiology (considered non-consanguinity
      related). We estimated adjusted hazard ratios for the diseases in children of
      foreign-born women compared with children of Danish-born women. RESULTS: Compared
      with offspring of Danish-born women, the risk of a consanguinity-related disease
      was significantly increased in children of foreign-born women, although the
      absolute risk was low. The risk of non-consanguinity-related diseases did not
      differ between the groups compared. CONCLUSIONS: The findings support the
      hypothesis that consanguinity accounts for some, however a minor part, of the
      disparity in child mortality among migrants in Denmark.

PMID- 25970350
TI  - Fabrication of mesoporous Li2S-C nanofibers for high performance Li/Li2S cell
      cathodes.
AB  - A Li2S electrode is a very promising cathode for Li-ion batteries. However, the
      high voltage needed to activate Li/Li2S cells represents a challenging problem.
      Here, we report for the first time a mesoporous Li2S-C nanofiber composite with
      72 wt% Li2S. The assembled Li/Li2S cells showed a low and stable voltage plateau
      of 2.51 V for the first charge and can deliver a high initial discharge capacity
      of ~800 mA h g(-1). 

PMID- 25970352
TI  - Corrigenda.

PMID- 25970353
TI  - Corrigenda.

PMID- 25970351
TI  - Three-Dimensional Cell Entrapment as a Function of the Weight Percent of Peptide
      Amphiphile Hydrogels.
AB  - The design of scaffolds which mimic the stiffness, nanofiber structure, and
      biochemistry of the native extracellular matrix (ECM) has been a major objective
      for the tissue engineering field. Furthermore, mimicking the innate three
      dimensional (3D) environment of the ECM has been shown to significantly altered
      cellular response compared to that of traditional two-dimensional (2D) culture.
      We report the development of a self-assembling, fibronectin-mimetic, peptide
      amphiphile nanofiber scaffold for 3D cell culture. To form such a scaffold, 5 mol
      % of a bioactive PR_g fibronectin-mimetic peptide-amphiphile was mixed with 95
      mol % of a diluent peptide-amphiphile (E2) whose purpose was to neutralize
      electrostatic interactions, increase the gelation kinetics, and promote cell
      survival. Atomic force microscopy verified the fibrilar structure of the gels,
      and the mechanical properties were characterized for various weight percent (wt
      %) formulations of the 5 mol % PR_g-95 mol % E2 peptide-amphiphile mixture. The
      0.5 wt % formulations had an elastic modulus of 429.0 +/- 21.3 Pa whereas the 1.0
      wt % peptide-amphiphile hydrogels had an elastic modulus of 808.6 +/- 38.1 Pa.
      The presence of entrapped cells in the gels decreased the elastic modulus, and
      the decrease was a function of cell loading. Although both formulations supported
      cell proliferation, the 0.5 wt % gels supported significantly greater NIH3T3/GFP
      fibroblast cell proliferation throughout the gels than the 1.0 wt % gels.
      However, compared to the 0.5 wt % formulations, the 1.0 wt % hydrogels promoted
      greater increases in mRNA expression and the production of fibronectin and type
      IV collagen ECM proteins. This study suggests that this fibronectin-mimetic
      scaffold holds great promise in the advancement of 3D culture applications and
      cell therapies. 

PMID- 25970354
TI  - Tuberculosis of the cervical spine.
AB  - A 25-year-old male state-prisoner presented with altered mental status, right
      neck pain, and uncontrolled hypertension. 

PMID- 25970355
TI  - Collateral damage: balancing the risks and the benefits of antimicrobial
      prophylaxis.

PMID- 25970356
TI  - Ultrasound-Assisted Percutaneous Needle Fasciotomy for Dupuytren's Contracture.
AB  - Although percutaneous needle fasciotomy for Dupuytren's contracture is a simple,
      inexpensive procedure, it is a blind procedure with risks including injury to
      nerves, arteries, and tendons. The authors describe a novel technique using
      ultrasound as an adjunct to percutaneous fasciotomy for Dupuytren's contracture.
      Generally, patients have no postoperative restrictions other than to avoid
      submerging their hands for 48 hours. To date, the authors have noted, in 66
      cases, no permanent complete nerve dysfunction following needle aponeurotomy
      using ultrasound assistance. Recurrence of the disease is the most common
      complication, occurring at a higher rate than with open procedures. Ultrasound
      mapping of the digital neurovascular structures can be successfully used as an
      adjunct to help prevent these neurovascular complications.

PMID- 25970357
TI  - Use of auxiliary locking plates for the treatment of unstable pertrochanteric
      femur fractures.
AB  - Pertrochanteric femur fractures are successfully treated by orthopedic surgeons
      worldwide, but maintaining the reduction status or fixation of the greater
      trochanter is sometimes difficult in unstable cases in elderly patients. Several
      biomechanical advantages have been reported in locking plates when compared with
      conventional plates; locking plates provide angular and axial stability, better
      rigidity, and no toggling, and they preserve periosteal blood supply. The authors
      describe the use of auxiliary locking plates in unstable pertrochanteric femur
      fractures in elderly patients. Mini locking plates are simple, straightforward,
      and versatile enough to be used in elderly patients.

PMID- 25970358
TI  - Cartilage lesions of the patella: management after acute patellar dislocation.
AB  - Articular cartilage injuries to the patella are frequent after patellar
      dislocation. The management of these acute cartilage injuries in the acute
      setting can be challenging. It is well documented that acute fixation is the
      optimal choice for treatment of osteochondral injuries. This article discusses
      the challenges and potential treatment options for acute chondral/osteochondral
      injuries to the patella after acute patellar dislocation.

PMID- 25970359
TI  - Effect of Topical Tranexamic Acid in Reducing Bleeding and Transfusions in TKA.
AB  - Intravenous tranexamic acid (TXA) has been identified to be effective in total
      knee arthroplasty (TKA), but the effect of topical application is still unclear.
      Therefore, the authors conducted a meta-analysis to assess the effect of topical
      TXA in TKA. Twelve trials with a total of 1179 knees were included. The results
      revealed that the application of topical TXA in TKA significantly reduced total
      blood loss by a mean of 280.65 mL and reduced transfusions without increasing the
      risks of deep venous thrombosis and pulmonary embolism. Topical TXA also reduced
      postoperative drain output by a mean of 194.59 mL and lowered postoperative
      hemoglobin drop by a mean of 0.66 g/dL. In addition, subgroup analysis showed
      that high-concentration TXA may be better at reducing bleeding and transfusions
      than low-concentration TXA. Therefore, the authors concluded that topical TXA can
      effectively reduce bleeding and transfusion rate in TKA without increasing the
      risk of deep venous thrombosis and pulmonary embolism, and high-concentration (20
      mg/mL or more) topical TXA is recommended.

PMID- 25970360
TI  - Arthroscopic transosseous rotator cuff repair: technical note, outcomes, and
      complications.
AB  - The goal of this study was to review the authors' initial experience with
      arthroscopic transosseous rotator cuff repair. Thirty-one patients with full
      thickness rotator cuff tears underwent arthroscopic transosseous rotator cuff
      repair over a 15-month period. Preoperatively, demographics and subjective scores
      were recorded. Postoperatively, pain levels, subjective shoulder values,
      satisfaction scores, American Shoulder and Elbow Surgeons (ASES) scores,
      complications, and reoperations were noted with a minimum 2-year follow-up. The
      relationships between pre- and intraoperative variables and outcome scores were
      determined with univariate analysis. Average patient age was 56 years, and 23
      patients (74%) were men. Twenty patients (65%) underwent primary rotator cuff
      repair, and 11 patients (35%) underwent revision repair. Average time to follow
      up was 26 months. Average preoperative pain level and subjective shoulder value
      were 5.1 of 10 and 35%, respectively. Average postoperative scores included pain
      level of 0.9 of 10, subjective shoulder value of 84%, satisfaction score of 90.6
      of 100, and ASES score of 86.3 of 100. There were 3 (9.7%) major and 2 (6%) minor
      complications. Patients undergoing revision rotator cuff repair had significantly
      worse outcomes (pain level, subjective shoulder value, ASES score; P<.05)
      compared with those undergoing primary repair, and cortical augmentation did not
      significantly affect outcome. Overall, outcomes after arthroscopic transosseous
      rotator cuff repair are good, although patients undergoing revision repair do not
      have the same outcomes as those undergoing primary cuff repair. The procedure is
      not without complications (9.7% major, 6% minor complications). Cortical
      augmentation may be used to supplement fixation, although it does not necessarily
      affect outcomes. Patients without such augmentation may be at increased risk for
      suture cutout through the bone.

PMID- 25970361
TI  - Secondary osteosarcoma: is there a predilection for the chondroblastic subtype?
AB  - Osteosarcoma is the most common form of primary bone cancer in the adolescent and
      young adult patient population. Outcomes in patients with secondary osteosarcoma
      are inferior compared with outcomes in patients with primary osteosarcoma. The
      goal of this study was to investigate whether there is a predilection for the
      chondroblastic histologic subtype in secondary osteosarcoma. A retrospective
      chart review was performed to identify cases of secondary osteosarcoma treated at
      1 institution from 1991 to 2012. Histologic subtypes were evaluated by a
      pathologist, and a review of the literature was also performed to identify the
      histologic subclassification of additional series of secondary osteosarcomas. Of
      a total of 131 cases of osteosarcoma, 9 (6.9%) were identified as a secondary
      malignancy. Only 2 cases (22%) were identified as chondroblastic variants,
      although 6 (67%) showed some degree of chondroid differentiation. Of the 3 cases
      meeting the criteria for postradiation osteosarcoma, 2 (67%) were identified as
      chondroblastic variants and all 3 showed some degree of chondroid
      differentiation. Five other studies evaluating histologic subtypes in
      postradiation osteosarcoma showed a cumulative frequency of 20% for the
      chondroblastic variant. Although the study results did not support the hypothesis
      of an association between secondary osteosarcoma and the chondroblastic subtype,
      the high proportion of cases of postradiation osteosarcoma with the
      chondroblastic subtype and the even higher proportion showing some degree of
      chondroid differentiation are noteworthy features of this disease.

PMID- 25970362
TI  - Elective hand surgery after axillary lymph node dissection for cancer.
AB  - After axillary lymph node dissection (ALND), patients are cautioned against
      ipsilateral interventional procedures to avoid the theoretical increased risk of
      postoperative complications, particularly lymphedema. The authors' goal was to
      evaluate the complications of elective hand surgery after ALND. The authors
      reviewed patients presenting to their hand clinic from 1998 to 2011, selecting
      those with a diagnosis of breast cancer or melanoma and a history of previous
      ALND; the authors excluded those treated nonoperatively and those treated with
      elective surgery in the contralateral hand. Average age of the 22 patients
      meeting the criteria (20 with a history of breast cancer, 6 with preexisting
      lymphedema) was 53.9 years (range, 26.7 to 73.6 years) at the time of ALND and
      63.1 years (range, 31.7 to 83.5 years) at the time of hand surgery. Average
      interval between surgeries was 9.2 years (range, 8 days to 37.3 years). Follow-up
      averaged 9.2 months (range, 8 days to 41.7 months). Fifteen patients were
      surveyed for long-term postoperative results (average surgery-to-survey interval,
      4.3 years [range, 1 to 11.9 years]). Fifteen patients had uneventful
      postoperative recoveries, 4 had peri-incisional erythema requiring oral
      antibiotics, 1 had incisional pain and scarring, 1 had chronic wound-healing
      issues, and 1 had a dehiscence requiring a return to the operating room. In the
      15 patients who completed the follow-up survey, there was no disease exacerbation
      in the 3 patients with preexisting lymphedema, and there were no new cases of
      lymphedema. Routine minor hand surgery did not result in lymphedema and did not
      increase existing lymphedema in these patients with previous ipsilateral ALND,
      but almost one-third of them had short-term complications in the postoperative
      recovery period.

PMID- 25970363
TI  - A sclerotic rim provides mechanical support for the femoral head in
      osteonecrosis.
AB  - Osteonecrotic collapse of the femoral head is a common refractory disease in
      orthopedics, and the occurrence of collapse is an important factor in the
      prognosis of this condition. Osteonecrotic collapse of the femoral head can be
      delayed or prevented by the formation of a sclerotic rim. This study used finite
      element analysis to evaluate the mechanical role of a proximal sclerotic rim on
      stress on the femoral head. The study used a healthy man who underwent computed
      tomography of both hips to generate 3-dimensional finite element models with
      different proportions of proximal rim sclerosis (0%, 30%, 50%, and 100%). Using a
      negative directional mechanical load of 400 N along the Z-axis, total
      deformation, deformation in the negative Z-axial direction (ie, direction of
      longitudinal compression), maximum principal stress, minimum principal stress,
      and contact pressure on necrotic tissue were evaluated. For 0%, 30%, 50%, and
      100% rim sclerosis, total femoral head deformation was 0.21, 0.205, 0.20, and
      0.19 mm, respectively, and maximum principal stress in compression was 9.83,
      9.67, 9.16, and 9.05 MPa, respectively. Increases in proximal rim sclerosis
      decreased all of the measured outcomes. These results suggest that proximal rim
      sclerosis provides effective mechanical support for the femoral head, offers
      mechanical protection for necrotic tissue, decreases deformation of the femoral
      head, and delays or prevents collapse in osteonecrosis.

PMID- 25970364
TI  - Does Intraoperative Fluoroscopy Optimize Limb Length and the Precision of
      Acetabular Positioning in Primary THA?
AB  - Reduced limb length discrepancy and more accurate cup positioning are purported
      benefits of using fluoroscopy for total hip arthroplasty (THA). The authors
      compared limb length discrepancy and cup position in 200 patients (group I,
      posterior approach without fluoroscopy; group II, anterior supine approach with
      fluoroscopy) who underwent primary THA. Mean limb length discrepancy was 2.7 mm
      (SD, 5.2 mm; range, -9.8 to 20.9 mm) and 0.7 mm (SD, 3.7 mm; range, -11.8 to 10.5
      mm) for groups I and II, respectively (P=.002). In group I, 7% of hips had limb
      length discrepancy greater than 1 cm compared with 3% in group II. Mean cup
      inclination measured 40.8 degrees  (SD, 5.0 degrees ; range, 26.1 degrees -53.7
      degrees ) in group I and 43.4 degrees  (SD, 5.6 degrees ; range, 31.3 degrees 
      55.9 degrees ) in group II (P=.008). In group I, 96% of cups had inclination
      within 10 degrees  of the mean compared with 92% in group II (P=.24). Mean
      anteversion measured 35.3 degrees  (SD, 7.1 degrees ; range, 17.8 degrees -60.7
      degrees ) in group I and 25.9 degrees  (SD, 8.2 degrees ; range, 1.5 degrees 
      44.8 degrees ) in group II (P=.0001). In group I, 87% of hips exhibited
      anteversion within 10 degrees  of the mean compared with 76% in group II
      (P=.045). Although the anterior approach with intraoperative fluoroscopy reduced
      mean limb length discrepancy, the clinical significance of this reduction is
      unclear. Fluoroscopy reduced the incidence of limb length discrepancy greater
      than 1 cm. However, the use of fluoroscopy did not help to improve the precision
      of cup positioning.

PMID- 25970365
TI  - Impact of a weekly reading program on orthopedic surgery residents' in-training
      examination.
AB  - In response to a decline in individual residents' performance and overall program
      performance on the Orthopaedic In-Training Examination (OITE), the authors'
      department initiated a daily literature reading program coupled with weekly tests
      on the assigned material. The goal of this study was to assess the effect of the
      reading program on individual residents' scores and the training program's OITE
      scores. The reading program consisted of daily review articles from the Journal
      of the American Academy of Orthopaedic Surgeons, followed by a weekly written
      examination consisting of multiple-choice or fill-in-the-blank questions. All
      articles were selected and all questions were written by the departmental chair.
      A questionnaire was given to assess residents' perceptions of the weekly tests.
      As a result of implementing the reading program for a 10-month period, residents'
      subsequent performance on the OITE significantly improved (mean score increase,
      4, P<.0001; percentile score increase, 11, P=.0007). The difference in mean score
      was significant for residents in postgraduate years 3, 4, and 5. A statistically
      significant correlation was found between weekly test scores and performance on
      the OITE, with a significant correlation between weekly test scores and OITE
      percentile ranking. The study results also showed a positive correlation between
      reading test attendance and weekly test scores. Residents' anonymous
      questionnaire responses also demonstrated the reading program to be a valuable
      addition to the residency training curriculum. In conclusion, the study strongly
      supports the benefits of a weekly reading and examination program in enhancing
      the core knowledge of orthopedic surgery residents.

PMID- 25970366
TI  - Total hip arthroplasty after lower extremity amputation.
AB  - There are approximately 1.6 million lower extremity amputees in the United
      States. Lower extremity amputees are subject to increased physical demands
      proportional to their level of amputation. Lower extremity amputees have a 6-fold
      higher risk of developing radiographic osteoarthritis in the ipsilateral hip and
      a 2-fold risk of developing radiographic osteoarthritis in contralateral hip when
      compared with the non-amputee population. Additionally, there is a 3-fold
      increased risk of developing radiographic osteoarthritis in the ipsilateral hip
      after an above knee amputation when compared with a below knee amputation. The
      authors retrospectively reviewed 35 total hip arthroplasties after lower
      extremity amputation. The mean clinical follow-up was 5.3+/-4.0 years. The mean
      time from lower extremity amputation to total hip arthroplasty was 12.2+/-12.8
      years after a contralateral amputation and 5.4+/-6.0 years after an ipsilateral
      amputation (P=.050). The mean time to total hip arthroplasty was 15.6+/-15.4
      years after an above knee amputation and 6.4+/-6.1 years after a below knee
      amputation (P=.021). There was a statistically significant improvement in the
      mean Harris Hip Score from 35.9+/-21.8 to 76.8+/-12.8 with total hip arthroplasty
      after a contralateral amputation (P<.001). There also was a statistically
      significant improvement in the mean Harris Hip Score from 25.4+/-21.7 to 78.6+/
      17.1 with total hip arthroplasty after an ispilateral amputation (P<.001). Three
      (17.7%) total hip arthroplasties after a contralateral amputation and 2 (11.1%)
      total hip arthroplasties after an ipsilateral amputation required revision total
      hip arthroplasty. Patients with an ipsilateral amputation or a below knee
      amputation progress to total hip arthroplasty faster than those with a
      contralateral amputation or an above knee amputation, respectively. Lower
      extremity amputees experience clinically significant improvements with total hip
      arthroplasty after lower extremity amputation.

PMID- 25970367
TI  - Reconstruction with modular megaprostheses for sarcomas of the lower extremity.
AB  - Limb-preserving surgery using modular megaprostheses for the reconstruction of
      large skeletal defects is currently the preferred treatment for sarcomas. The
      authors report the postoperative outcomes after skeletal resection for lower
      extremity sarcomas and the use of the METS cemented modular implant system
      (Stanmore Implants, Hertfordshire, United Kingdom) for reconstruction. They
      retrospectively studied 52 consecutive patients operated on from 2003 to 2012.
      There were 27 distal femur prostheses, 13 proximal femur, 11 proximal tibia, and
      1 total femur implants. Patients were followed for a mean of 4.3 years. Overall
      patient survival, prosthesis survival, limb salvage rate, and secondary
      complications were documented. Five years postoperatively, prosthesis survival
      was 79%. Complications warranting implant revision surgery were documented in 15%
      of patients, whereas complications warranting surgery of any kind were observed
      in 27% of the patients. Nonmechanical complications, namely local relapse of the
      tumor and prosthetic infection, were the most common cause of prosthetic failure,
      accounting for 88% of major revision surgeries and 100% of amputations.
      Mechanical complications were rare, observed in only 6% of patients. No patients
      required secondary revision surgery. The limb salvage rate was 89%. Overall
      patient survival was 79% at 5 years and 71% at 10 years. The low risk for
      mechanical complications and the high limb salvage rate support the use of the
      METS modular megaprostheses for the reconstruction of skeletal defects following
      lower limb sarcoma surgery.

PMID- 25970368
TI  - Effect of an emergency department-based electronic system for musculoskeletal
      consultation on facilitating care for common injuries.
AB  - Access to musculoskeletal consultation in the emergency department (ED) is a
      nationwide problem. In addition, consultation from a subspecialist may be delayed
      or may not be available, which can slow down the ED flow and reduce patient
      satisfaction. The purpose of this study was to review the 1-year results of a
      change in the authors' institutional practice to reduce subspecialty consultation
      for select musculoskeletal problems while still ensuring adequate patient follow
      up in orthopedic or plastic surgery clinics for patients not seen by these
      services in the ED. The authors hypothesized that select injuries could be safely
      managed in the ED by using an electronic system to ensure appropriate follow-up
      care. Using Kaizen methodology, a multidisciplinary group (including ED staff,
      orthopedics, plastic surgery, pediatrics, nursing, radiology, therapy, and
      administration) met to improve care for select musculoskeletal injuries. A system
      was agreed on in which ED providers managed select musculoskeletal injuries
      without subspecialist consultation. Follow-up was organized using an electronic
      system, which facilitated communication between the ED staff and the secretarial
      staff of the subspecialist departments. Over a 1-year period, 150 patients were
      treated using this system. Charts and radiographs were reviewed for missed
      injuries. Radiographic review revealed 2 missed injuries. One patient had
      additional back pain and a lumbar spine fracture was found during the
      subspecialist follow-up visit; it was treated nonoperatively. Another patient
      appeared to have scapholunate widening on the injury radiograph that was not
      appreciated in the ED. Of the 150 patients, 51 were seen in follow-up by a
      subspecialist at the authors' institution. An electronic system to organize
      follow-up with a subspecialist allowed the ED providers to deliver safe and
      effective care for simple musculoskeletal injuries.

PMID- 25970369
TI  - Unicortical versus bicortical locked plate fixation in midshaft clavicle
      fractures.
AB  - Higher rates of poor outcomes in displaced midshaft clavicle fractures treated
      nonoperatively have recently been reported. Along with expanding indications for
      operative fixation and increasing application of locked plate constructs, it is
      unknown whether complications related to bicortical penetration of the clavicle
      can be avoided using unicortical fixation. The purpose of this study is to
      compare the biomechanical properties of unicortical and bicortical fixation in
      precontoured vs manually contoured locking clavicle plates. Forty-eight Sawbone
      composite human clavicle specimens (item #3408; Pacific Research Laboratories,
      Vashon, Washington) with a midshaft clavicle osteotomy were reduced and plated in
      8 specimens each using a bicortical and unicortical fixation for each of 3 locked
      plate constructs (3.5-mm LCP Reconstruction Plate; 3.5-mm LCP Superior Clavicle
      Plate; 3.5-mm LCP Superior Anterior Clavicle Plate; Synthes, Inc, West Chester,
      Pennsylvania). Specimens were tested for stiffness in axial torsion and
      cantilever bending and then loaded to failure in 3-point bending. Data were
      analyzed using 2-way analysis of variance and Tukey's test (P<.05). No
      significant differences were found between unicortical and bicortical fixation in
      failure load, cantilever bending, and cross body stiffness. Bicortical fixation
      was significantly stiffer than unicortical fixation in torsion only for the same
      plates. Significant differences also existed between plates in torsion.
      Unicortical locked plate fixation may be a reasonable option in the treatment of
      displaced midshaft clavicle fracture fixation to avoid complications associated
      with posteroinferior hardware penetration following clavicle fracture fixation
      based on the biomechanical performance of these constructs. However, it remains
      unclear whether these differences will be clinically significant.

PMID- 25970370
TI  - Effect of simulated early weight bearing on micromotion and pullout strength of
      uncemented distal femoral stems.
AB  - The effect of simulated early weight bearing on both micromotion and pullout
      strength of uncemented distal femoral stems was evaluated in this study. The
      effect of stem endosteal contact and bone quality on implant pullout strength was
      also analyzed. A randomized matched-pair study was performed using 8 bilateral
      pairs of fresh human cadaveric femoral specimens. Each specimen pair was dual
      energy x-ray absorptiometry scanned, uniformly implanted, fluoroscopically
      imaged, and randomly assigned to the cycled or uncycled group. The cycled group
      received 5000 cycles of axial compressive loading (to 700 N) and the
      contralateral side was not cycled. Micromotion was monitored during cycling and
      compared with a failure threshold (150 um), and all implants underwent direct
      axial distraction (pullout) testing. During cycling, minimal micromotion was
      observed with an asymptotic decrease in differential motion between the first and
      last 50 cycles. Both cycled and uncycled groups demonstrated no statistical
      difference in average pullout force (4888+/-2124 N vs 4367+/-1154 N; P=.43). The
      percentage of cortical contact for each implant was determined from panoramic
      fluoroscopy images using digital image analysis software. Contact area for the
      distal third of the stem showed the highest correlation with pullout force and
      with predicting pullout force. Bone quality did not correlate with pullout force
      (r(2)=0.367) or stem contact area (r(2)=0.394). In sum, press-fit uncemented
      femoral stems did not loosen or demonstrate decreased pullout strength with early
      weight bearing simulated by cyclical axial compressive loading.

PMID- 25970371
TI  - Bilateral arthroscopic rotator cuff repair using a single-stage procedure.
AB  - Bilateral rotator cuff tears requiring repair are not uncommon. Typically, these
      tears have been treated with staged surgeries. However, in appropriately selected
      cases, single-stage repair is preferable because it reduces costs, the number of
      admissions, total hospitalization, and rehabilitation time. It can also reduce
      patient suffering by providing relief with a single procedure. The authors
      compared 10 patients with a mean age of 55 years who had bilateral symptomatic
      rotator cuff tear and underwent single-stage bilateral arthroscopic cuff repair
      (group A) with 17 patients with a mean age of 55 years who had unilateral
      symptomatic rotator cuff tear and underwent unilateral arthroscopic cuff repair
      (group B). Clinical assessment was performed preoperatively and at 3, 6, and 12
      months postoperatively with the visual analog scale, the University of California
      Los Angeles (UCLA) score, and the Korean shoulder score. Overall function, pain,
      and strength were improved significantly in both groups. Although the difference
      in visual analog scale score between both groups decreased during follow-up, this
      score was significantly lower in group B (P=.026). At initial follow-up, the UCLA
      score was higher in group A. However, at the last follow-up, this score was
      significantly higher in group B (P<.001). The Korean shoulder score was
      significantly higher in group A at all follow-up times (P<.001). The study
      findings showed that single-stage bilateral rotator cuff repair is a preferable
      option in appropriately selected patients. It can provide satisfactory results
      without additional complications, and it does not lead to longer hospitalization
      or rehabilitation than unilateral repair.

PMID- 25970372
TI  - Computerized Virtual Surgery Planning for ORIF of Proximal Humeral Fractures.
AB  - The authors evaluated the effectiveness of computerized virtual planning for open
      reduction and internal fixation (ORIF) of proximal humeral fractures. Between
      June 2011 and July 2013, a total of 46 patients with proximal humeral fractures
      were included in the current study. Preoperatively, fracture data were obtained
      via computed tomography (CT) reconstruction. Based on the dataset obtained from
      CT scanning, the 3-dimensional model of fractures was constructed and virtual
      segmentation, restoration, and internal fixation were performed. All eligible
      cases were treated by ORIF with locking plates. Intraoperatively, operative time,
      blood loss, and fluoroscope frequency were recorded. Postoperatively, the
      curative effect was evaluated by quality of fracture restoration reconstruction
      and plate position. In addition, fracture healing time and complications were
      recorded in the follow-up period. Average operative time was 85.6 minutes, and
      intraoperative blood loss ranged from 60 to 150 mL. Postoperatively, 1 patient
      experienced avascular necrosis, and no cases of screw penetration or screw
      loosening were observed. The coincidence rate of plate position was 91.3%
      according to height and 95.7% based on the position of the intertubercular sulcus
      and greater tuberosity. At the end of the follow-up period, mean shoulder
      function score was 83.9 (range, 58-96). Eighty-seven percent of patients had an
      excellent or good outcome. Computerized virtual planning facilitated ORIF and
      showed good results for patients with complex proximal humeral fractures. It may
      be a favorable option for treating fractures of the proximal humerus.

PMID- 25970373
TI  - Platelet-rich plasma does not decrease blood loss in total knee arthroplasty.
AB  - This study was designed to assess the use of platelet-rich plasma (PRP) during
      primary total knee arthroplasty (TKA). The authors hypothesized that this would
      result in less blood loss and greater hemoglobin and hematocrit levels at
      discharge and would potentially decrease the length of hospital stay. Leukocyte
      rich PRP was used during the procedure and at wound closure. Two surgeons
      performed all procedures in a similar fashion. Two different TKA implants were
      used. Each surgeon used the same implant throughout the study. A limited medial
      parapatellar approach was used and drains were used at closure. No tranexamic
      acid preparations were used. Continuous passive motion machines were used in all
      patients during their hospital stay. A total of 102 consecutive TKAs were
      performed. The study group (n=46) consecutively received the PRP injections
      during the TKA, whereas the control group (n=47) did not. Hemoglobin and
      hematocrit levels were obtained pre- and postoperatively. Estimated blood loss
      was recorded during surgery, and the auto-collection reinfusion drain system
      output was measured. The length of hospital stay was collected and recorded. The
      study showed that hemoglobin and hematocrit levels were not different when
      comparing study and control groups. Age and sex differences were insignificant.
      Finally, no statistical difference was seen for the estimated blood loss and
      hospital stay between the 2 groups. Platelet-rich plasma use during TKA does not
      decrease hospital stay or reduce estimated blood loss in the perioperative
      period.

PMID- 25970374
TI  - Arachnoiditis ossificans after spinal surgery.
AB  - This article presents an unusual case of arachnoiditis ossificans after spinal
      surgery. A case of arachnoiditis ossificans secondary to lumbar fixation and
      decompression surgery for the treatment of multilevel lumbar fractures is
      reported and the relevant literature is reviewed. A 29-year-old man who
      previously underwent posterior pedicle screw fixation and fusion for multiple
      lumbar spine fractures reported lower back stiffness and discomfort 23 months
      postoperatively. A laminectomy was performed at L2 and at L3-L4. At L2, bone
      fragments from the burst fracture had injured the dural sac and some nerve roots.
      A posterolateral fusion was performed using allogeneic bone. Postoperatively,
      there were no signs of fever, infection, or systemic inflammatory responses.
      Arachnoiditis ossificans of the thecal sac from L1-L5 was diagnosed by magnetic
      resonance imaging and computed tomography at the 2-year follow-up. His
      postoperative neurological status progressively improved and he regained motor
      and sensory functions. Because of neurological improvements, fixation hardware
      was removed without further decompression. The authors report a case of
      arachnoiditis ossificans secondary to lumbar fixation and decompression surgery,
      which involved a large region. Arachnoiditis ossificans is a relatively rare
      disorder with unclear etiologies and limited treatment options. Spinal surgical
      intervention of arachnoiditis ossificans should be carefully considered because
      it may lead to poor outcomes and multiple revision surgeries.

PMID- 25970375
TI  - Bilateral extensor mechanism disruption after total knee arthroplasty in two
      morbidly obese patients.
AB  - Disruption of the extensor mechanism as a result of patellar tendon or quadriceps
      tendon rupture is an uncommon but devastating complication after total knee
      arthroplasty. Treating a disrupted extensor mechanism can be challenging,
      particularly in patients who are morbidly obese, due to an increased risk of
      postoperative complications. Therefore, despite the debilitating nature of
      extensor mechanism disruption, many community surgeons do not feel comfortable
      pursuing more complex cases like revision total knee arthroplasty with extensor
      mechanism allograft on morbidly obese patients, and consequently many of these
      patients are referred to tertiary-care centers for reconstruction secondary to
      the complexity of this patient cohort. The authors report 2 cases of bilateral
      extensor mechanism disruption after total knee arthroplasty in patients who are
      morbidly obese. One patient experienced trauma leading to her initial rupture;
      however, her contralateral atraumatic disruption was subsequently diagnosed at a
      later date. The second patient did not experience trauma leading to either of her
      extensor mechanism disruptions. Despite substantial medical comorbidities and
      morbid obesity, revision total knee arthroplasties with extensor mechanism
      allografts were recommended in both cases in a staged bilateral fashion. The
      surgical technique is described and the unique challenges afforded by the marked
      obesity are detailed. The current literature on this subject is reviewed. Despite
      early complications related to recumbency, this report serves as an example of
      successful repairs of extensor mechanism disruptions in patients who are morbidly
      obese, suggesting that extensor mechanism allograft is viable even in patients
      with high risk of complications.

PMID- 25970376
TI  - Greater Trochanteric Fragmentation After Failed Metal-on-Metal Hip Arthroplasty.
AB  - Adverse reaction to metal debris (ARMD) involving the hip joint has emerged as an
      important reason for failure and revision among patients with metal-on-metal
      (MOM) hip arthroplasty. To the authors' knowledge, there are no reports of
      adverse radiographic sequelae in the greater trochanter subsequent to revision
      for ARMD. The authors describe clinical and radiographic findings in 2 patients
      who developed greater trochanteric fragmentation 1 to 2 years after conversion of
      their failed MOM hips to polyethylene bearings. Both patients had solid
      pseudotumors with tissue necrosis. Several reports describe various clinical
      features of ARMD. Although poor outcomes have been demonstrated after some MOM
      revisions, to the authors' knowledge, no reports document greater trochanter
      fragmentation in ARMD. The current patients highlight the fact that tissue damage
      occurring with MOM bearing hips can involve bone in addition to soft tissue even
      after a pseudotumor has been removed and serum metal levels have decreased to
      normal levels after revision. Unlike the greater trochanteric fractures
      historically associated with polyethylene wear and osteolysis, no evidence of
      bone cysts or lesions was found prior to the fractures and neither fracture
      healed with conservative treatment. For these 2 patients, the authors believe the
      tissue necrosis included both soft tissue and bone. The necrotic bone resorbed
      gradually after removal of the MOM bearing, resulting in bone fragmentation with
      ongoing symptoms. These patients emphasize and remind us that damage is not only
      limited to soft tissues, but also includes bone. Surgeons should be aware of this
      radiographic finding and the associated clinical symptoms.

PMID- 25970377
TI  - Colour Doppler Ultrasonography as a Tool to Assess Luteal Function in Santa Ines
      Ewes.
AB  - The aim of this study was to evaluate luteal dynamics in the Santa Ines ewes
      using colour Doppler (CD) ultrasonography. Oestrus was synchronized in
      nulliparous females (n = 18), and subsequently, they were only teased (n = 6) or
      teased and mated (n = 12). Blood samples were collected daily for plasma
      progesterone (P4 ) concentrations. Ultrasonographic images of corpora lutea (CL)
      in CD mode were obtained for further analysis in its largest diameter. The CD
      mode allowed an early sequential monitoring of CL that was visualized by the
      first time 0.77 +/- 0.62 days after ovulation, with luteal area 29.68 +/- 13.21
      mm(2) . During the luteogenesis, a progressive increase was observed, followed by
      a plateau of luteal area, vascularization area and plasma concentrations of P4
      reaching maximum values in D11 (124.0 +/- 38.0 mm(2) , 52.78 +/- 24.08 mm(2) and
      11.23 +/- 4.89 ng/ml, respectively). In the luteolysis, the plasma concentrations
      of P4 decreased sharply, whereas luteal and vascularization area gradually. The
      vascularization area was positively correlated with plasma concentrations of P4
      during the luteogenesis (r = 0.22) and luteolysis (r = 0.48). The luteal dynamics
      of Santa Ines ewes showed patterns similar to those observed in other sheep
      breeds studied. The CD ultrasonography has the potential to be used as a tool to
      assess luteal function in sheep. 

PMID- 25970378
TI  - Human nuclear ARGONAUTE 2 interacts in vivo only with small RNAs and not with
      DNA.

PMID- 25970379
TI  - Atopic and nonatopic eczema in adolescence: is there a difference?
AB  - BACKGROUND: There is limited information on clinical manifestations of atopic
      eczema (AE) and non-AE in teenagers. OBJECTIVES: To describe the characteristics
      of adolescent eczema in the general population and to identify potential
      differences between AE and non-AE in teenagers. METHODS: Overall, 3108 teenagers
      were included from the population-based BAMSE cohort and 2529 of these teenagers
      provided blood samples for analysis of specific IgE. At age 16 years, the
      teenagers answered questionnaires regarding the symptoms of eczema, asthma and
      rhinitis for the previous year. RESULTS: The prevalence of eczema in adolescence
      was 9.6% (n = 297). More girls than boys had eczema (12.5% vs. 6.5%; P < 0.001).
      The age at onset was usually within the first 2 years of life (48.8%), but onset
      in adolescence was also common (25.6%). Eczema was mild in 72.7% of cases,
      moderate in 16.8% and severe in 10.4%. Body folds were most frequently affected
      (73.4%). More than half of the teenagers with eczema had AE (59%). The teenagers
      with AE had more severe and more chronic eczema. Onset in infancy was most common
      in AE and onset in adolescence was most common in non-AE. There were no major
      differences in location or seasonal variance between AE and non-AE in
      adolescence. CONCLUSIONS: AE is more common than non-AE among teenagers. More
      than one in four teenagers with eczema has moderate-to-severe disease. Onset in
      adolescence is common, especially for non-AE. AE in adolescence has an earlier
      onset and is more chronic and more severe than non-AE.

PMID- 25970380
TI  - Short-term risk of cancer among women with previous gestational diabetes: a
      population-based study.
AB  - AIMS: To evaluate the relationship between gestational diabetes (GDM) and
      incidence of cancer in women within the first decade postpartum. METHODS: This
      population-based retrospective cohort study compared the risk of cancer in women
      with GDM with that of a matched control group comprising pregnant women without
      diabetes. We included women from Ontario, Canada aged 20-50 years with no history
      of cancer who had given birth between 1995 and 2008 (N = 149 049). Women with GDM
      (N = 49 684) were matched on age and year of giving birth, in a ratio of 1:2, to
      pregnant women without diabetes (N = 99 365). RESULTS: Over a median 8-year
      follow-up, there were a total of 2927 (1.5%) cancers. After adjustment for
      covariates, we found no significant difference in overall risk of cancer between
      women with GDM and matched control subjects; however, GDM was associated with a
      significantly greater risk of thyroid cancer (adjusted hazard ratio 1.24, 95% CI
      1.05, 1.46) and a significantly lower risk of premenopausal breast cancer (hazard
      ratio 0.86, 95% CI 0.75, 0.98) compared with matched control subjects.
      CONCLUSIONS: This large population-based study did not find a greater risk of
      cancers among women with GDM during the first decade postpartum; however, GDM was
      associated with a higher risk of thyroid cancer and a lower risk of premenopausal
      breast cancer. Further studies are needed to confirm these findings.

PMID- 25970381
TI  - The proper locus of professionalization: the individual or the institutions?

PMID- 25970383
TI  - Characterizing clinical ethics consultations: the need for a standardized
      typology of cases.

PMID- 25970382
TI  - Ethics consultation in pediatrics: long-term experience from a pediatric oncology
      center.
AB  - There is little information about the content of ethics consultations (EC) in
      pediatrics. We sought to describe the reasons for consultation and ethical
      principles addressed during EC in pediatrics through retrospective review and
      directed content analysis of EC records (2000-2011) at St. Jude Children's
      Research Hospital. Patient-based EC were highly complex and often involved
      evaluation of parental decision making, particularly consideration of the risks
      and benefits of a proposed medical intervention, and the physician's fiduciary
      responsibility to the patient. Nonpatient consultations provided guidance in the
      development of institutional policies that would broadly affect patients and
      families. This is one of the few existing reviews of the content of pediatric EC
      and indicates that the distribution of ethical issues and reasons for moral
      distress are different than with adults. Pediatric EC often facilitates complex
      decision making among multiple stakeholders, and further prospective research is
      needed on the role of ethics consultation in pediatrics. 

PMID- 25970384
TI  - Pediatric clinical ethics consultations at an academic medical center: does one
      size fit all?

PMID- 25970385
TI  - Making meaning from experience: a working typology for pediatrics ethics
      consultations.

PMID- 25970386
TI  - Rethinking pediatric ethics consultations.

PMID- 25970387
TI  - Ethics Consults in Pediatrics and Neonatology Are More Varied and Complex Than
      Those Reported at St. Jude's Children's Research Hospital.

PMID- 25970388
TI  - They're Not Just Little Adults: Special Considerations in Pediatric Clinical
      Ethics Consultation.

PMID- 25970389
TI  - A cautionary note on anonymous referrals for clinical ethics case consultations.

PMID- 25970390
TI  - Eliciting parental values and preferences in the medical decision-making process.

PMID- 25970391
TI  - Ethical concerns raised among pediatric heart failure clinicians.

PMID- 25970393
TI  - The Significance of the ASBH's Code of Ethics for Healthcare Ethics Consultants.

PMID- 25970394
TI  - Professionalization of clinical ethics consultation: defining (down) the code.

PMID- 25970392
TI  - A code of ethics for health care ethics consultants: journey to the present and
      implications for the field.
AB  - For decades a debate has played out in the literature about who bioethicists are,
      what they do, whether they can be considered professionals qua bioethicists, and,
      if so, what professional responsibilities they are called to uphold. Health care
      ethics consultants are bioethicists who work in health care settings. They have
      been seeking guidance documents that speak to their special relationships/duties
      toward those they serve. By approving a Code of Ethics and Professional
      Responsibilities for Health Care Ethics Consultants, the American Society for
      Bioethics and Humanities (ASBH) has moved the professionalization debate forward
      in a significant way. This first code of ethics focuses on individuals who
      provide health care ethics consultation (HCEC) in clinical settings. The
      evolution of the code's development, implications for the field of HCEC and
      bioethics, and considerations for future directions are presented here. 

PMID- 25970395
TI  - Becoming a competent ethics consultant: up to code?

PMID- 25970396
TI  - The duty of competence and the role of simulated ethics case consultation.

PMID- 25970397
TI  - Fostering the ethics of ethics consultants in health care: an ongoing
      participatory approach.

PMID- 25970398
TI  - A critique of the (aspirational) code of ethics.

PMID- 25970399
TI  - A code of ethics for ethicists: what would Pierre Bourdieu say? "Do not misuse
      social capital in the age of consortia ethics".

PMID- 25970400
TI  - Codes for health care consultation: which definitions? Which experiences?

PMID- 25970401
TI  - The Mysterious Disappearance of the Object of Inquiry: Jacobs and Arora's Defense
      of Circumcision.

PMID- 25970402
TI  - A 1000-Year Carbon Isotope Rainfall Proxy Record from South African Baobab Trees
      (Adansonia digitata L.).
AB  - A proxy rainfall record for northeastern South Africa based on carbon isotope
      analysis of four baobab (Adansonia digitata L.) trees shows centennial and
      decadal scale variability over the last 1,000 years. The record is in good
      agreement with a 200-year tree ring record from Zimbabwe, and it indicates the
      existence of a rainfall dipole between the summer and winter rainfall areas of
      South Africa. The wettest period was c. AD 1075 in the Medieval Warm Period, and
      the driest periods were c. AD 1635, c. AD 1695 and c. AD1805 during the Little
      Ice Age. Decadal-scale variability suggests that the rainfall forcing mechanisms
      are a complex interaction between proximal and distal factors. Periods of higher
      rainfall are significantly associated with lower sea-surface temperatures in the
      Agulhas Current core region and a negative Dipole Moment Index in the Indian
      Ocean. The correlation between rainfall and the El Nino/Southern Oscillation
      Index is non-static. Wetter conditions are associated with predominantly El Nino
      conditions over most of the record, but since about AD 1970 this relationship
      inverted and wet conditions are currently associated with la Nina conditions. The
      effect of both proximal and distal oceanic influences are insufficient to explain
      the rainfall regime shift between the Medieval Warm Period and the Little Ice
      Age, and the evidence suggests that this was the result of a northward shift of
      the subtropical westerlies rather than a southward shift of the Intertropical
      Convergence Zone. 

PMID- 25970404
TI  - [CPAP-therapy affects body weight].

PMID- 25970403
TI  - A Single Protein S-acyl Transferase Acts through Diverse Substrates to Determine
      Cryptococcal Morphology, Stress Tolerance, and Pathogenic Outcome.
AB  - Cryptococcus neoformans is an opportunistic yeast that kills over 625,000 people
      yearly through lethal meningitis. Host phagocytes serve as the first line of
      defense against this pathogen, but fungal engulfment and subsequent intracellular
      proliferation also correlate with poor patient outcome. Defining the interactions
      of this facultative intracellular pathogen with host phagocytes is key to
      understanding the latter's opposing roles in infection and how they contribute to
      fungal latency, dissemination, and virulence. We used high-content imaging and a
      human monocytic cell line to screen 1,201 fungal mutants for strains with altered
      host interactions and identified multiple genes that influence fungal adherence
      and phagocytosis. One of these genes was PFA4, which encodes a protein S-acyl
      transferase (PAT), one of a family of DHHC domain-containing proteins that
      catalyzes lipid modification of proteins. Deletion of PFA4 caused dramatic
      defects in cryptococcal morphology, stress tolerance, and virulence.
      Bioorthogonal palmitoylome-profiling identified Pfa4-specific protein substrates
      involved in cell wall synthesis, signal transduction, and membrane trafficking
      responsible for these phenotypic alterations. We demonstrate that a single PAT is
      responsible for the modification of a subset of proteins that are critical in
      cryptococcal pathogenesis. Since several of these palmitoylated substrates are
      conserved in other pathogenic fungi, protein palmitoylation represents a
      potential avenue for new antifungal therapeutics. 

PMID- 25970405
TI  - [Need for better adjustments of prevention strategies on individual risk
      profile].

PMID- 25970406
TI  - [More stringent protocol does not reduce mortality].

PMID- 25970407
TI  - [47-year-old man with sudden onset of fever and skin alterations].

PMID- 25970408
TI  - [From dyspesia to gastric cancer--various causes, challenging diagnosis].

PMID- 25970409
TI  - [Chronic upper abdominal pain: Diagnostic and therapeutic algorithm].
AB  - Between 20% and 40% of the population have chronic or recurrent upper abdominal
      pain, frequently in combination with other dyspeptic symptoms. In about 50% of
      patients, who visit a doctor because of these complaints, symptoms are caused by
      an organic disease, whereas the other patients suffer from functional
      disturbances. Currently, the Rome III-criteria are established for diagnosis of
      functional dyspepsia. They request epigastric pain burning, bothersome
      postprandial fullness and/or early satiety and absence of structural disease that
      is likely to explain the symptoms. These criteria need to have been fulfilled for
      the previous 3 months with symptom onset at least 6 months before diagnosis. For
      exclusion of organic disease performance of an upper endoscopy is required. Some
      experts also recommend to investigate routine laboratory parameters and to
      perform an abdominal ultrasound investigation. Only in young patients who present
      with typical and moderate symptoms and have no alarm symptoms, probatory therapy
      without previous technical investigations and, thus, without final establishment
      of the diagnosis, may be considered. If they do not respond adequately within 4
      weeks, these patients also have to undergo further diagnostic testing.
      Therapeutic options for functional dyspepsia are limited. They include the clear
      explanation of the diagnosis, consideration of factors that trigger or ameliorate
      symptoms and application of drugs such as certain herbal remedies, acid
      suppressing drugs and/or prokinetics.

PMID- 25970410
TI  - [Chronic abdominal pain: these diseases can be the cause].

PMID- 25970411
TI  - [Drug-induced dyspepsia].
AB  - Gastrointestinal symptoms are among the most common side effects of drugs. There
      is a broad spectrum of symptoms. Patients often report upper abdominal pain, an
      early sense of satiety, epigastric discomfort or pain in the upper abdomen or
      behind the breastbone, flatulence, diarrhoea or constipation. Some of these
      symptoms are attributed to the stomach or upper abdomen by the patient and/or the
      physician. "Stomach pain", pain in the epigastric region, occurs in most cases in
      combination with other symptoms such as a feeling of pressure in the upper
      abdomen or bloating, early satiety, nausea or vomiting--a combination called
      dyspepsia. Given the high frequency of these symptoms in the general population
      and the large number of medications many patients are taking, it can be very
      difficult in a given patient to differentiate between drug-induced side effects
      and spontaneously occurring symptoms.

PMID- 25970412
TI  - [Occupational medicine with passion--Prof. Dr. Andreas Zober for his 70th
      birthday].

PMID- 25970413
TI  - [How to do: The diagnostic lumbar puncture].
AB  - The diagnostic lumbar puncture is an important diagnostic tool in various
      neurological diseases, such as inflammatory processes of the central nervous
      system. Considering relevant contraindications and performed in a standardised
      manner, the lumbar puncture can be regarded as a safe procedure with few side
      effects. The additional diagnostic yield is also of relevance in numerous non
      neurological conditions. 

PMID- 25970414
TI  - [Rat-bite fever--two cases of infection with Streptobacillus moniliformis within
      two months].
AB  - Medical history and clinical findings | Two cases of the rarely diagnosed
      Streptobacillus moniliformis infection (rat bite or haverhill fever) emerged
      within two months in Stuttgart. The first patient presented with typical
      symptoms, i.e., fever and arthralgia. The second patient, however, was afebrile
      with severe back pain and fatigue as only symptoms. None of the patients reported
      rat bites or other animal contacts. Examinations | Physical examination did not
      reveal any focus of infection in the first patient. Further examinations could
      not be completed. Suspected diagnosis was therefore "unclear, most likely viral
      infection". In the case of the second patient, ultrasound revealed an engorged
      right kidney and urinary obstruction. Upon concomitant detection of Escherichia
      coli in the urine, pyelonephritis was suspected. Laboratory parameters were not
      indicative in neither case. Detection of the infectious agents was accomplished
      by blood cultures and subsequent identification by mass spectrometry, albeit
      after discharge of the patients. Treatment and course | The first patient left
      the hospital against the doctors' advice the day after his admission. The second
      patient improved under ciprofloxacin and metamizole therapy and was discharged
      after five days with the recommendation to continue the antibiotic therapy.
      Conclusion | Cases of rat bite or haverhill fever are difficult to diagnose when
      no rat bites are recognized. Seroprevalence data of S. moniliformis infection
      would be desirable to estimate how often atypical or subclinical cases of this
      potentially lethal infection go undiagnosed.

PMID- 25970415
TI  - [Hyperhydration and dialysis in acute kidney failure].
AB  - Despite the advances in critical care medicine, the hospital mortality in
      patients with acute kidney injury (AKI) requiring dialysis remains high.
      Depending on the underlying disease the in-house mortality is reported to be up
      to 80%. Several observational studies demonstrated an association between
      mortality and fluid overload. A primary mechanism of interest is that fluid
      overload causes tissue edema and subsequent reduction of perfusion, oxygenation
      and nutrient delivery. This results in further renal damage. In addition, fluid
      overload-related dilution within the extracellular space causes artificially low
      serum creatinine, which masks AKI diagnosis. As a consequence, renal protective
      management strategies are deferred, which further aggravates kidney injury. This
      aggravation of renal damage subsequently increases the mortality. This review
      discusses the role of fluid overload for outcomes in critically ill patients as
      described in the current literature and assesses criteria for the initiation of
      renal replacement therapy in this critically ill population.

PMID- 25970416
TI  - [Stroke prevention with direct oral anticoagulants in patients with non-valvular
      atrial fibrillation].
AB  - The development of the direct oral anticoagulants (DOACs) represents one of the
      major breakthroughs in modern medicine over the last decade. Compared to vitamin
      K antagonists, all DOACs (dabigatran as a thrombin-Inhibitor, rivaroxaban,
      apixaban and edoxaban as factor Xa inhibitors) are much easier to handle due to
      their pharmacological properties. All DOACS are more efficacious and safer as
      vitamin K antagonists as demonstrated in the pivotal studies in more than 71,000
      patients. Particularly the much lower risk of intracerebral bleeding
      complications is the reason why the DOACs should be preferred over vitamin K
      antagonists in patients with non-valvular atrial fibrillation.

PMID- 25970417
TI  - [Behavior-based prevention of chronic diseases].
AB  - BACKGROUND: Tobacco smoking, unhealthy alcohol drinking, overweight, and lack of
      physical activity add to more than 50% of myocardial infarction and are the most
      prevalent avoidable factors related to cancer. Cardiovascular disease and cancer
      may be curbed by preventive action in addition to medical care. The aim of this
      contribution is to present the elements that constitute prevention: participation
      rates, intervention programs, and outcomes. Criteria for outcomes include
      intention to change behaviors, the behavior change, total lifetime and time of
      life free of chronic disease and disability. RESULTS: Evidence reveals that
      national preventive action should include legal action, environmental change, and
      direct health behavior change. The measures include reducing the appeal of and
      increasing the protection against risky products. Such provisions will reduce
      cardiovascular disease and cancer incidence. Direct behavior change includes
      counseling individuals in the general population. Evidence is provided by cohort,
      modeling, and controlled trial data. All three approaches revealed success of
      prevention. Collaboration of prevention and medical care will add to synergies.
      CONCLUSION: A deficit of action exists. Effective preventive action should be
      implemented into practice, cooperation between prevention and medical care be
      supported.

PMID- 25970418
TI  - [LDL-Cholesterol--Is there an "LDL hypothesis"?].
AB  - The term "LDL-Hypothesis" is frequently used to describe the association between
      LDL cholesterol (LDL-C) and cardiovascular outcomes. In the light of recent
      results of randomized trials the question arises whether the term hypothesis is
      still adequate. Considering the causal importance of LDL for the pathogenesis of
      atherosclerosis, epidemiological evidence and the clear genetic association of
      LDL-C with cardiovascular risk as well as the large statin trials and the
      reduction of events by a non-statin intervention in the IMPROVE-IT study, the
      term "hypothesis" appears to be outdated and should be replaced by "LDL
      causality". 

PMID- 25970419
TI  - [Complementary medicine and cancer].

PMID- 25970420
TI  - [Are the immunization services offered to students at university hospitals in
      Germany sufficient?].
AB  - OBJECTIVE: Healthcare professionals have an increased risk of acquiring
      infectious diseases and can also serve as a source of infection to their
      patients. The German Standing Committee on Vaccination (STIKO) recommends that
      healthcare professionals should be sufficiently vaccinated against vaccine
      preventable infections. Also medical students belong to this target group. For
      this reason their vaccination status should be checked and -if necessary-
      completed before working with patients. METHODS: Anonymous questionnaire-based
      survey among occupational physicians at university hospitals in Germany provided
      information about immunization services and the acceptance of vaccination.
      RESULTS: In total 34 of 37 university hospitals (response 91.9%) participated in
      this survey. Except one university hospital, all offered occupation-related
      vaccinations to their medical students. While hepatitis B vaccination was offered
      in all 33 university hospitals with immunization services, more than 44% did not
      offer at all or only to restricted groups (e. g. students with an internship in
      Pediatrics) vaccinations against measles-mumps-rubella (MMR). In 50% of the
      university hospitals this also applied to the pertussis vaccinations. Only 33% of
      university hospitals reported to collect data for a precise vaccination coverage
      assessment. A seasonal influenza vaccination program for medical staff was
      established at 30 (88%) university hospitals, but of these only 56% included
      medical students. CONCLUSION: The forceful implementation of evidence-based
      vaccination recommendations supports the reduction of nosocomial infections and
      outbreaks. In view of the WHO goal of eliminating measles and a documented
      increased risk of acquiring measles, it is alarming that university hospitals do
      not offer MMR-vaccines to their medical students at all or only to restricted
      groups. There is also a need to improve health services in respect to offering
      influenza and pertussis vaccinations to medical students and collecting data to
      better assess vaccination coverage.

PMID- 25970421
TI  - [Diabetes screening and prevention in a large chemical company].
AB  - INTRODUCTION: Diabetes is with 6 million cases in Germany one of the most common
      and most expensive chronic diseases. Studies presume a high number of unreported
      cases. Early detection of diabetes with a specific screening method is very
      important. In Germany family physicians offer a preventive check-up starting at
      the age of 35 years but only 19% males participate. From this background the BASF
      department for Occupational Medicine and Health Protection introduced for all
      35.000 employees at the headquarter, in Ludwigshafen a general health check
      focused on the early detection of lifestyle diseases. METHODS: From April 2011 to
      June 2013 12.114 employees participated in the general health check offered by
      the medical department (2.530 women, 9.584 men). All participants filled out a
      questionnaire named "Findrisk" a scientifically validated questionnaire which
      focuses on risk factors for diabetes. Furthermore, the blood glucose and the
      HbA1c of the participants have also been checked in a laboratory test RESULTS:
      Following the Findrisk criteria the results are: 1.368 employees had an elevated
      risk of 17%, 854 employees a risk factor of 33% and 131 employees a risk factor
      of 33%. In 1.533 employees (13,2% of all participants) we diagnosed a prediabetes
      with an elevated HbA1c-parameter between 5.7 to 6,4%. In 243 employees a manifest
      diabetes disease with HbA1c of > than 6,5% was diagnosed. DISCUSSION: We found
      out that diabetes prevention within the workplace setting is helpful to detect
      prediabetes and diabetes earlier than family doctors outside the company are able
      to do.Occupational physicians have the opportunity to inform the employees on
      risks for lifestyle diseases at an early stage when they are still healthy
      (primary prevention).For secondary prevention surveillance and clearance
      examination can be easily combined with screening tests for diabetes. For further
      diagnostics and therapy the family doctors will be addressed. This system helps
      individuals to prevent negative health effects, it helps the employer to reduce
      incapacity time and it also helps the state health system to safe money for
      therapy and rehabilitation.

PMID- 25970422
TI  - Creamy Yellow Concretions in Axillary Hair.

PMID- 25970423
TI  - Detection of Low-Level Mixed-Population Drug Resistance in Mycobacterium
      tuberculosis Using High Fidelity Amplicon Sequencing.
AB  - Undetected and untreated, low-levels of drug resistant (DR) subpopulations in
      clinical Mycobacterium tuberculosis (Mtb) infections may lead to development of
      DR-tuberculosis, potentially resulting in treatment failure. Current phenotypic
      DR susceptibility testing has a theoretical potential for 1% sensitivity, is not
      quantitative, and requires several weeks to complete. The use of "single molecule
      overlapping reads" (SMOR) analysis with next generation DNA sequencing for
      determination of ultra-rare target alleles in complex mixtures provides increased
      sensitivity over standard DNA sequencing. Ligation free amplicon sequencing with
      SMOR analysis enables the detection of resistant allele subpopulations at >=0.1%
      of the total Mtb population in near real-time analysis. We describe the method
      using standardized mixtures of DNA from resistant and susceptible Mtb isolates
      and the assay's performance for detecting ultra-rare DR subpopulations in DNA
      extracted directly from clinical sputum samples. SMOR analysis enables rapid near
      real-time detection and tracking of previously undetectable DR sub-populations in
      clinical samples allowing for the evaluation of the clinical relevance of low
      level DR subpopulations. This will provide insights into interventions aimed at
      suppressing minor DR subpopulations before they become clinically significant. 

PMID- 25970424
TI  - MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of
      Human Colon Cancer Cells.
AB  - Although cancer is a genetic disease, epigenetic alterations are involved in its
      initiation and progression. Previous studies have shown that reprogramming of
      colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy.
      Therefore, cancer reprogramming may be a useful treatment for chemo- or
      radiotherapy-resistant cancer cells. It was also reported that the introduction
      of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR) 302s
      and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs
      are smaller than the genes of transcription factors, making them possibly
      suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer
      cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell
      proliferation and invasion and the stimulation of the mesenchymal-to-epithelial
      transition phenotype in colon cancer cells. Importantly, the introduction of the
      ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and
      histone modification events. Furthermore, in vivo administration of the
      ribonucleotides in mice elicited the induction of cancer cell apoptosis, which
      involves the mitochondrial Bcl2 protein family. The present study shows that the
      introduction of miR-302s and miR-369s could induce cellular reprogramming and
      modulate malignant phenotypes of human colorectal cancer, suggesting that the
      appropriate delivery of functional small-sized ribonucleotides may open a new
      avenue for therapy against human malignant tumors. 

PMID- 25970425
TI  - Structure and dynamics of minke whale surfacing patterns in the Gulf of St.
      Lawrence, Canada.
AB  - Animal behavioral patterns can help us understand physiological and ecological
      constraints on animals and its influence on fitness. The surfacing patterns of
      aquatic air-breathing mammals constitute a behavioral pattern that has evolved as
      a trade-off between the need to replenish oxygen stores at the surface and the
      need to conduct other activities underwater. This study aims to better understand
      the surfacing pattern of a marine top predator, the minke whale (Balaenoptera
      acutorostrata), by investigating how their dive duration and surfacing pattern
      changes across their activity range. Activities were classified into resting,
      traveling, surface feeding and foraging at depth. For each activity, we
      classified dives into short and long dives and then estimated the temporal
      dependence between dive types. We found that minke whales modified their
      surfacing pattern in an activity-specific manner, both by changing the expression
      of their dives (i.e. density distribution) and the temporal dependence
      (transition probability) between dive types. As the depth of the prey layer
      increased between activities, the surfacing pattern of foraging whales became
      increasingly structured, going from a pattern dominated by long dives, when
      feeding at the surface, to a pattern where isolated long dives were followed by
      an increasing number of breaths (i.e. short dives), when the whale was foraging
      at depth. A similar shift in surfacing pattern occurred when prey handling time
      (inferred from surface corralling maneuvers) increased for surface feeding
      whales. The surfacing pattern also differed between feeding and non-feeding
      whales. Resting whales did not structure their surfacing pattern, while traveling
      whales did, possibly as a way to minimize cost of transport. Our results also
      suggest that minke whales might balance their oxygen level over multiple, rather
      than single, dive cycles. 

PMID- 25970426
TI  - Carotid intima-media thickness, a marker of subclinical atherosclerosis, and
      particulate air pollution exposure: the meta-analytical evidence.
AB  - INTRODUCTION: Studies on the association between atherosclerosis and long-term
      exposure to ambient air pollution suggest that carotid intima-media thickness
      (CIMT), a marker of subclinical atherosclerosis, is positively associated with
      particulate matter (PM) exposure. However, there is heterogeneity between the
      different studies concerning the magnitude of this association. We performed a
      meta-analysis to determine the strength of the association between CIMT and
      particulate air pollution. METHODS: We queried PubMed citation database and Web
      of Knowledge up to March 2015 in order to identify studies on CIMT and
      particulate air pollution. Two investigators selected and computerized all
      relevant information, independently. Eight of the reviewed epidemiological
      publications provided sufficient details and met our inclusion criteria.
      Descriptive and quantitative information was extracted from each selected study.
      The meta-analysis included 18,349 participants from eight cohorts for the cross
      sectional association between CIMT and PM and 7,268 participants from three
      cohorts for the longitudinal analysis on CIMT progression and PM exposure.
      RESULTS: The average exposure to PM2.5 in the different study populations ranged
      from 4.1 to 20.8 ug/m3 and CIMT averaged (SD) 0.73 (0.14) mm. We computed a
      pooled estimate from a random-effects model. In the combined cross-sectional
      studies, an increase of 5 ug/m3 PM2.5 was associated with a 1.66% (95% CI: 0.86
      to 2.46; P<0.0001) thicker CIMT, which corresponds to an average increase of 12.1
      um. None of the studies moved the combined estimate outside the confidence
      interval of the overall estimate. A funnel plot suggested absence of publication
      bias. The combined longitudinal estimate showed for each 5 ug/m3 higher PM2.5
      exposure, a 1.04 um per year (95% CI: 0.01 to 2.07; P=0.048) greater CIMT
      progression. CONCLUSION: Our meta-analysis supports the evidence of a positive
      association between CIMT, a marker of subclinical atherosclerosis, and long-term
      exposure to particulate air pollution.

PMID- 25970428
TI  - A Novel Objective Method of Estimating the Age of Mandibles from African
      Elephants (Loxodonta africana Africana).
AB  - The importance of assigning an accurate estimate of age and sex to elephant
      carcasses found in the wild has increased in recent years with the escalation in
      levels of poaching throughout Africa. Irregularities identified in current ageing
      techniques prompted the development of a new method to describe molar progression
      throughout life. Elephant mandibles (n = 323) were studied and a point near the
      distal dental alveolus was identified as being most useful in ranking each jaw
      according to molar progression. These 'Age Reference Lines' were then associated
      with an age scale based on previous studies and Zimbabwean mandibles of known
      age. The new ranking produced a single age scale that proved useful for both male
      and female mandibles up to the maximum lifespan age of 70-75 years. Methods to
      aid in molar identification and the sexing of found jaws were also identified. 

PMID- 25970427
TI  - The Association between Infections and General Cognitive Ability in Young Men - A
      Nationwide Study.
AB  - BACKGROUND: Infections and activated immune responses can affect the brain
      through several pathways that might also affect cognition. However, no large
      scale study has previously investigated the effect of infections on the general
      cognitive ability in the general population. METHODS: Danish nationwide registers
      were linked to establish a cohort of all 161,696 male conscripts during the years
      2006-2012 who were tested for cognitive ability, which was based on logical,
      verbal, numerical and spatial reasoning at a mean age of 19.4 years. Test scores
      were converted to a mean of 100.00 and with a standard deviation (SD) of 15. Data
      were analyzed as a cohort study with severe infections requiring hospitalization
      as exposure using linear regression. RESULTS: Adjusted effect sizes were
      calculated with non-exposure to severe infections as reference, ranging from 0.12
      SD to 0.63 SD on general cognitive ability. A prior infection was associated with
      significantly lower cognitive ability by a mean of 1.76 (95%CI: -1.92 to -1.61;
      corresponding to 0.12 SD). The cognitive ability was affected the most by the
      temporal proximity of the last infection (P<0.001) and by the severity of
      infection measured by days of admission (P<0.001). The number of infections were
      associated with decreased cognitive ability in a dose-response relationship, and
      highest mean differences were found for >=10 hospital contacts for infections
      (Mean: -5.54; 95%CI: -7.20 to -3.89; corresponding to 0.37 SD), and for >=5
      different types of infections (Mean: -9.44; 95%CI: -13.2 to -5.69; corresponding
      to 0.63 SD). Hospital contacts with infections had occurred in 35% of the
      individuals prior to conscription. CONCLUSIONS: Independent of a wide range of
      possible confounders, significant associations between infections and cognitive
      ability were observed. Infections or related immune responses might directly
      affect the cognitive ability; however, associated heritable and environmental
      factors might also account for the lowered cognitive ability.

PMID- 25970429
TI  - Prevalence and predictors of verbal aggression in a secure mental health service:
      Use of the HCR-20.
AB  - Despite evidence about the negative effects of verbal aggression in mental health
      wards there is little research about its prevalence or about the factors that
      predict the behaviour among inpatients. This study aimed to determine the
      prevalence of verbal aggression in a secure mental health service, and to examine
      the relationship of verbal aggression with risk factors for aggression in the
      risk assessment tool HCR-20 in order to establish whether, and with which
      factors, the behaviour can be predicted. Verbal aggression was measured using the
      Overt Aggression Scale (OAS) over a 3-month period across a heterogeneous patient
      group (n = 613). Over half the patients (n = 341, 56%) engaged in 1594 incidents
      of verbal aggression. The HCR-20 total, clinical, and risk management subscale
      scores predicted verbal aggression, though effect sizes were not large. Item
      outcome analysis revealed that impulsivity, negative attitudes, and non
      compliance with medication were the best predictors of verbal aggression and,
      therefore, should be targeted for intervention. There are key synergies between
      factors predicting verbal aggression and the core mental health nursing role.
      Nurses, therefore, are in a prime position to develop and implement interventions
      that may reduce verbal aggression in mental health inpatients.

PMID- 25970430
TI  - Location contexts of user check-ins to model urban geo life-style patterns.
AB  - Geo-location data from social media offers us information, in new ways, to
      understand people's attitudes and interests through their activity choices. In
      this paper, we explore the idea of inferring individual life-style patterns from
      activity-location choices revealed in social media. We present a model to
      understand life-style patterns using the contextual information (e. g. location
      categories) of user check-ins. Probabilistic topic models are developed to infer
      individual geo life-style patterns from two perspectives: i) to characterize the
      patterns of user interests to different types of places and ii) to characterize
      the patterns of user visits to different neighborhoods. The method is applied to
      a dataset of Foursquare check-ins of the users from New York City. The co
      existence of several location contexts and the corresponding probabilities in a
      given pattern provide useful information about user interests and choices. It is
      found that geo life-style patterns have similar items-either nearby neighborhoods
      or similar location categories. The semantic and geographic proximity of the
      items in a pattern reflects the hidden regularity in user preferences and
      location choice behavior. 

PMID- 25970431
TI  - Immunocytochemical Diagnosis of Limbal Stem Cell Deficiency: Comparative Analysis
      of Current Corneal and Conjunctival Biomarkers.
AB  - PURPOSE: To evaluate and compare corneal and conjunctival biomarkers for
      immunocytochemical diagnosis of limbal stem cell deficiency (LSCD). METHODS: In
      accordance with the current literature, we selected K12 as the corneal biomarker
      and K7/K13/K19/MUC5AC as the conjunctival ones. The specificity and accuracy for
      each biomarker were assessed and compared on 10 healthy subjects and tissues of
      deceased donors. Twelve eyes of 9 patients clinically suspected of LSCD were
      enrolled. Epithelial cells (ECs) from the central cornea were collected using
      impression cytology (IC) and assessed for each biomarker. The presence of
      conjunctival cells in the central cornea was diagnostic proof of LSCD, whereas
      the detection of corneal residual cells would quantify the degree of LSCD.
      RESULTS: K12 and K7/K13/MUC5AC are, respectively, highly specific of corneal and
      conjunctival differentiation, whereas K19 is not. Normal corneal ECs are not
      desquamative enough to be suitable for IC. Among 12 eyes with suspected LSCD, 84%
      (10 of 12) of IC samples were suitable for analysis. K3/K7/K19 immunostaining was
      positive in 100%, MUC5AC in 40%, and K12 was never observed. CONCLUSIONS:
      Clinical examination can lead to misdiagnosis of LSCD. Immunocytochemical
      detection of K7/K13 on corneal ECs collected by IC is reproducible, noninvasive,
      and highly effective in this indication, but without any quantification of the
      degree of the disease. This time-consuming technique requires skilled technicians
      and laboratory facilities, reserving it for planned limbal reconstruction.

PMID- 25970432
TI  - Intraocular Lens Opacification After Endothelial Keratoplasty as Analyzed by
      Environmental Scanning Electron Microscopy.
AB  - PURPOSE: To describe a case of hydrophilic intraocular lens (IOL) opacification
      based on IOL analysis after Descemet stripping automated endothelial
      keratoplasty. METHODS: A 60-year-old woman had uneventful phacoemulsification
      after the implantation of a hydrophilic IOL (Akreos-Adapt; Bausch & Lomb) into
      both eyes. Because of postoperative corneal decompensation in the right eye, 2
      Descemet stripping automated endothelial keratoplasty operations were performed
      within 1 year. After the second procedure, the graft was not well attached,
      requiring an intracameral injection of air on day 3. After 1 year, opacification
      was observed on the superior 2/3 of the anterior surface of the IOL, along with a
      significant decrease in visual acuity. The IOL was explanted 6 months after the
      opacification. RESULTS: Environmental scanning electron microscopy followed by x
      ray microanalysis revealed an organic biofilm on the surface of the IOL.
      CONCLUSIONS: To our knowledge, this is the first reported case in which the
      material deposited on the lens is organic rather than calcific.

PMID- 25970433
TI  - Spontaneous Resolution of Acute Corneal Hydrops in a Patient With Post-LASIK
      Ectasia.
AB  - PURPOSE: To describe a case of acute corneal hydrops in a patient with corneal
      ectasia after laser in situ keratomileusis (LASIK). METHODS: An observational
      study presenting clinical, slit-lamp, and optical coherence tomographic findings.
      RESULTS: A 66-year-old man with a history of moderate myopic astigmatism
      presented with a sudden loss of vision in his left eye 11 years after undergoing
      LASIK. He underwent a single enhancement in his left eye and was subsequently
      diagnosed with ectasia 9 years later. Slit-lamp examination demonstrated a small
      tear in the Descemet membrane with a large fluid-filled cleft separating the
      LASIK flap and extending to the flap edge. Because no aqueous humor leakage was
      detected, the patient was managed conservatively with eventual resolution of the
      fluid-filled cleft and return of 20/30 visual acuity. CONCLUSIONS: Acute corneal
      hydrops is a rare complication of post-LASIK corneal ectasia. In the absence of
      flap dehiscence and wound leak, such patients may be managed with simple
      observation.

PMID- 25970434
TI  - Does Corneal Collagen Cross-linking Reduce the Need for Keratoplasties in
      Patients With Keratoconus?
AB  - PURPOSE: To investigate whether the introduction of corneal collagen cross
      linking (CXL) influences the frequency of keratoplasties in patients with
      keratoconus. METHODS: Data were obtained from a cohort of patients from our
      corneal transplant registry. Two different periods were compared, 2005 to 2006
      (period 1) and 2013 to 2014 (period 2). Patients during period 1 had surgery
      before the introduction of CXL treatment, and patients in period 2 had surgery
      after this treatment was well established in our department. Age and gender were
      registered, and the Amsler-Krumeich classification system was applied to grade
      the degree of keratoconus. RESULTS: The total number of keratoplasties performed
      during period 1 was 137, and keratoconus was the cause of surgery in 55 eyes (55
      patients). The corresponding numbers in period 2 were 231 and 26 eyes (26
      patients), respectively. The difference in the number of keratoplasties for
      keratoconus in both periods was statistically significant (P = 0.003). There were
      no significant differences in the distributions of age and gender between both
      periods. In period 1, 63.6% of the eyes were graded as stage 4 in the Amsler
      Krumeich classification, compared with 96.2% in period 2 (P = 0.001).
      CONCLUSIONS: The frequency of keratoplasty for keratoconus has been more than
      halved in our department over the last decade. There is reason to believe that
      this reduction is for a great part caused by the introduction of CXL treatment.

PMID- 25970435
TI  - Clinical Characteristics and Bacteriological Profile of Moraxella Keratitis.
AB  - PURPOSE: Moraxella species are rare causative pathogens of severe sight
      threatening keratitis. The aim of this study was to analyze the clinical
      presentation, predisposing risk factors, in vitro antimicrobial susceptibility,
      and treatment associated with Moraxella keratitis. METHODS: We retrospectively
      reviewed 30 culture-proven cases of Moraxella keratitis from multiple centers in
      Japan. RESULTS: The mean age of the patients was 58.4 +/- 23.4 years. The most
      common ocular conditions were contact lens wearing (5 patients, 16.7%) and trauma
      (3 patients, 10.0%). Seven patients had diabetes mellitus. Sixteen patients
      exhibited hypopyon in association with the corneal focus. Ring-shaped
      infiltration was found in 9 patients (30.0%), and irregular or amoebic-shaped
      infiltration was observed in 13 patients (43.3%). Eight patients (26.7%) showed
      small round infiltrates. All Moraxella isolates were sensitive to
      fluoroquinolones and aminoglycosides. All were treated with a combination
      ophthalmic solution containing a fluoroquinolone, tobramycin, and cefmenoxime.
      Although no patients developed corneal perforation, the response to treatment was
      slow in all cases; the mean treatment period was 41.9 days. CONCLUSIONS: In
      Japan, Moraxella keratitis occurs in patients with contact lens wear, trauma, and
      diabetes mellitus. It presents as a small, round, ring-shaped, irregularly
      shaped, or amoebic-shaped focus. Moraxella species exhibit good susceptibility to
      fluoroquinolones and aminoglycosides. Because the treatment response may be very
      slow, these agents should be continued for a long period of time.

PMID- 25970436
TI  - Interplay of Immune Cells in Mooren Ulcer.
AB  - PURPOSE: To report the histopathological findings of the cornea with fulminant
      Mooren ulcer, an idiopathic autoimmune keratitis. METHODS: A 54-year-old woman
      was diagnosed with Mooren ulcer. Despite intensive immunosuppression, corneal
      perforation developed, and penetrating keratoplasty with a limbal tectonic graft
      was performed. The removed cornea was histopathologically evaluated for the
      phenotype of the cells infiltrating the lesion. RESULTS: Hematoxylin-eosin
      staining showed massive infiltration of inflammatory cells in the anterior
      corneal stroma and epithelial hyperplasia in the adjacent conjunctiva. Further
      analysis with immunohistochemistry indicated that the cells infiltrating the
      lesion included a number of CD4+ and CD8+ T lymphocytes, CD19+CD45+ B
      lymphocytes, and CD14+CD68+ macrophages. There were a few neutrophils and no
      CD56+ NK cells. CONCLUSIONS: Our findings suggest that multiple types of immune
      cells including T cells, B cells, and macrophages are involved in the
      pathogenesis of Mooren ulcer.

PMID- 25970437
TI  - Deep Anterior Lamellar Keratoplasty in Macular Corneal Dystrophy.

PMID- 25970438
TI  - The effect of 10 Hz repetitive transcranial magnetic stimulation of posterior
      parietal cortex on visual attention.
AB  - Repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal
      cortex (PPC) at frequencies lower than 5 Hz transiently inhibits the stimulated
      area. In healthy participants, such a protocol can induce a transient attentional
      bias to the visual hemifield ipsilateral to the stimulated hemisphere. This bias
      might be due to a relatively less active stimulated hemisphere and a relatively
      more active unstimulated hemisphere. In a previous study, Jin and Hilgetag (2008)
      tried to switch the attention bias from the hemifield ipsilateral to the
      hemifield contralateral to the stimulated hemisphere by applying high frequency
      rTMS. High frequency rTMS has been shown to excite, rather than inhibit, the
      stimulated brain area. However, the bias to the ipsilateral hemifield was still
      present. The participants' performance decreased when stimuli were presented in
      the hemifield contralateral to the stimulation site. In the present study we
      tested if this unexpected result was related to the fact that participants were
      passively resting during stimulation rather than performing a task. Using a fully
      crossed factorial design, we compared the effects of high frequency rTMS applied
      during a visual detection task and high frequency rTMS during passive rest on the
      subsequent offline performance in the same detection task. Our results were
      mixed. After sham stimulation, performance was better after rest than after task.
      After active 10 Hz rTMS, participants' performance was overall better after task
      than after rest. However, this effect did not reach statistical significance. The
      comparison of performance after rTMS with task and performance after sham
      stimulation with task showed that 10 Hz stimulation significantly improved
      performance in the whole visual field. Thus, although we found a trend to better
      performance after rTMS with task than after rTMS during rest, we could not reject
      the hypothesis that high frequency rTMS with task and high frequency rTMS during
      rest equally affect performance. 

PMID- 25970439
TI  - The effects of a calcium-rich pre-exercise meal on biomarkers of calcium
      homeostasis in competitive female cyclists: a randomised crossover trial.
AB  - : Cycling is recognised as a sport in which there is a high incidence of poor
      bone health. Sweat calcium losses may contribute to this. PURPOSE: To examine
      whether a calcium-rich pre-exercise meal attenuates exercise-induced
      perturbations of bone calcium homeostasis caused by maintenance of sweat calcium
      losses. METHODS: Using a randomized, counterbalanced crossover design, 32 well
      trained female cyclists completed two 90 min cycling trials separated by 1 day.
      Exercise trials were preceded 2 hours by either a calcium-rich (1352 +/- 53 mg
      calcium) dairy based meal (CAL) or a control meal (CON; 46 +/- 7 mg calcium).
      Blood was sampled pre-trial; pre-exercise; and immediately, 40 min, 100 min and
      190 min post-exercise. Blood was analysed for ionized calcium and biomarkers of
      bone resorption (Cross Linked C-Telopeptide of Type I Collagen (CTX-I), Cross
      Linked C-Telopeptide of Type II Collagen (CTX-II), Parathyroid Hormone (PTH), and
      bone formation (Procollagen I N-Terminal Propeptide (PINP)) using the established
      enzyme-linked immunosorbent assay technique. RESULTS: PTH and CTX-I increased
      from pre-exercise to post-exercise in both conditions but was attenuated in CAL
      (p < 0.001). PTH was 1.55 [1.20, 2.01] times lower in CAL immediately post
      exercise and 1.45 [1.12, 1.88] times lower at 40 min post-exercise. CTX-I was
      1.40 [1.15, 1.70] times lower in CAL at immediately post-exercise, 1.30 [1.07,
      1.57] times lower at 40 min post-exercise and 1.22 [1.00, 1.48] times lower at
      190 min post-exercise (p < 0.05). There was no significant interaction between
      pre-exercise meal condition and time point for CTX-II (p = 0.732) or PINP (p =
      0.819). CONCLUSION: This study showed that a calcium-rich pre-exercise breakfast
      meal containing ~1350 mg of calcium consumed ~90 min before a prolonged and high
      intensity bout of stationary cycling attenuates the exercise induced rise in
      markers of bone resorption--PTH and CTX-I. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry ACTRN12614000675628.

PMID- 25970440
TI  - The disastrous effects of salt dust deposition on cotton leaf photosynthesis and
      the cell physiological properties in the Ebinur Basin in Northwest China.
AB  - Salt dust in rump lake areas in arid regions has long been considered an extreme
      stressor for both native plants and crops. In recent years, research on the
      harmful effects of salt dust on native plants has been published by many
      scholars, but the effect on crops has been little studied. In this work, in order
      to determine the impact of salt dust storms on cotton, we simulated salt dust
      exposure of cotton leaves in Ebinur Basin in Northwest China, and measured the
      particle sizes and salt ions in the dust, and the photosynthesis, the structure
      and the cell physiological properties of the cotton leaves. (1) Analysis found
      that the salt ions and particle sizes in the salt dust used in the experiments
      were consistent with the natural salt dust and modeled the salt dust deposition
      on cotton leaves in this region. (2) The main salt cations on the surface and
      inside the cotton leaves were Na+, Ca2+, Cl- and SO42-, while the amounts of CO3-
      and HCO3- were low. From the analysis, we can order the quantity of the salt
      cations and anions ions present on the surface and inside the cotton leaves as
      Na+>Ca2+>Mg2+>K+ and Cl->SO42->HCO3->CO3-, respectively. Furthermore, the five
      salt dust treatment groups in terms of the total salt ions on both the surface
      and inside the cotton leaves were A(500g.m-2)>B(400g.m-2)>C(300g.m-2)>D(200g.m
      2)>E(100g.m-2)>F(0g.m-2). (3)The salt dust that landed on the surface of the
      cotton leaves can significantly influence the photosynthetic traits of Pn, PE,
      Ci, Ti, Gs, Tr, WUE, Ls, phi, Amax, k and Rady of the cotton leaves. (4)Salt dust
      can significantly damage the physiological functions of the cotton leaves,
      resulting in a decrease in leaf chlorophyll and carotenoid content, and
      increasing cytoplasmic membrane permeability and malondialdehyde (MDA) content by
      increasing the soluble sugar and proline to adjust for the loss of the cell
      cytosol. This increases the activity of antioxidant enzymes to eliminate harmful
      materials, such as the intracellular reactive oxygen and MDA, thus reducing the
      damage caused by the salt dust and maintaining normal physiological functioning.
      Overall, this work found that the salt dust deposition was a problem for the crop
      and the salt dust could significantly influence the physiological and biochemical
      processes of the cotton leaves. This will eventually damage the leaves and reduce
      the cotton production, leading to agricultural economic loss. Therefore,
      attention should be paid to salt dust storms in the Ebinur Basin and efficient
      measures should be undertaken to protect the environment. 

PMID- 25970441
TI  - Does Exonerating an Accused Researcher Restore the Researcher's Credibility?
AB  - Scientific misconduct appears to be on the rise. However, an accused researcher
      may later be exonerated. The present research examines to what extent
      participants adhere to their attitude toward a researcher who allegedly committed
      academic misconduct after learning that the researcher is innocent. In two
      studies, participants in an exoneration and an uncorrected accusation condition
      learned that the ethics committee of a researcher's university demanded the
      retraction of one of the researcher's articles, whereas participants in a control
      condition did not receive this information. As intended, this manipulation led to
      a more favorable attitude toward the researcher in the control compared to the
      exoneration and the uncorrected accusation conditions (pre-exoneration attitude).
      Then, participants in the exoneration condition learned that the researcher was
      exonerated and that the article was not retracted. Participants in the
      uncorrected accusation and the control condition were not informed about the
      exoneration. Results revealed that the exoneration effectively worked, in that
      participants in the exoneration condition had a more favorable attitude (post
      exoneration attitude) toward the researcher than did participants in the
      uncorrected accusation condition. Moreover, the post-exoneration attitude toward
      the researcher was similar in the exoneration and the control conditions.
      Finally, in the exoneration condition only, participants' post-exoneration
      attitude was more favorable than their pre-exoneration attitude. These findings
      suggest that an exoneration of an accused researcher restores the researcher's
      credibility. 

PMID- 25970442
TI  - Vitamin D status predicts 30 day mortality in hospitalised cats.
AB  - Vitamin D insufficiency, defined as low serum concentrations of the major
      circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated
      with the development of numerous infectious, inflammatory, and neoplastic
      disorders in humans. In addition, vitamin D insufficiency has been found to be
      predictive of mortality for many disorders. However, interpretation of human
      studies is difficult since vitamin D status is influenced by many factors,
      including diet, season, latitude, and exposure to UV radiation. In contrast,
      domesticated cats do not produce vitamin D cutaneously, and most cats are fed a
      commercial diet containing a relatively standard amount of vitamin D.
      Consequently, domesticated cats are an attractive model system in which to
      examine the relationship between serum 25(OH)D and health outcomes. The
      hypothesis of this study was that vitamin D status would predict short term, all
      cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together
      with a wide range of other clinical, hematological, and biochemical parameters,
      were measured in 99 consecutively hospitalised cats. Cats which died within 30
      days of initial assessment had significantly lower serum 25(OH)D concentrations
      than cats which survived. In a linear regression model including 12 clinical
      variables, serum 25(OH)D concentration in the lower tertile was significantly
      predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95%
      confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in
      the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D
      concentration status is an independent predictor of short term mortality in cats.

PMID- 25970443
TI  - Scaling Down to Scale Up: A Health Economic Analysis of Integrating Point-of-Care
      Syphilis Testing into Antenatal Care in Zambia during Pilot and National Rollout
      Implementation.
AB  - Maternal syphilis results in an estimated 500,000 stillbirths and neonatal deaths
      annually in Sub-Saharan Africa. Despite the existence of national guidelines for
      antenatal syphilis screening, syphilis testing is often limited by inadequate
      laboratory and staff services. Recent availability of inexpensive rapid point-of
      care syphilis tests (RST) can improve access to antenatal syphilis screening. A
      2010 pilot in Zambia explored the feasibility of integrating RST within
      prevention of mother-to-child-transmission of HIV services. Following successful
      demonstration, the Zambian Ministry of Health adopted RSTs into national policy
      in 2011. Cost data from the pilot and 2012 preliminary national rollout were
      extracted from project records, antenatal registers, clinic staff interviews, and
      facility observations, with the aim of assessing the cost and quality
      implications of scaling up a successful pilot into a national rollout. Start-up,
      capital, and recurrent cost inputs were collected, including costs of extensive
      supervision and quality monitoring during the pilot. Costs were analysed from a
      provider's perspective, incremental to existing antenatal services. Total and
      unit costs were calculated and a multivariate sensitivity analysis was performed.
      Our accompanying qualitative study by Ansbro et al. (2015) elucidated quality
      assurance and supervisory system challenges experienced during rollout, which
      helped explain key cost drivers. The average unit cost per woman screened during
      rollout ($11.16) was more than triple the pilot unit cost ($3.19). While quality
      assurance costs were much lower during rollout, the increased unit costs can be
      attributed to several factors, including higher RST prices and lower RST coverage
      during rollout, which reduced economies of scale. Pilot and rollout cost drivers
      differed due to implementation decisions related to training, supervision, and
      quality assurance. This study explored the cost of integrating RST into antenatal
      care in pilot and national rollout settings, and highlighted important
      differences in costs that may be observed when moving from pilot to scale-up. 

PMID- 25970444
TI  - Stimulus set meaningfulness and neurophysiological differentiation: a functional
      magnetic resonance imaging study.
AB  - A meaningful set of stimuli, such as a sequence of frames from a movie, triggers
      a set of different experiences. By contrast, a meaningless set of stimuli, such
      as a sequence of 'TV noise' frames, triggers always the same experience--of
      seeing 'TV noise'--even though the stimuli themselves are as different from each
      other as the movie frames. We reasoned that the differentiation of cortical
      responses underlying the subject's experiences, as measured by Lempel-Ziv
      complexity (incompressibility) of functional MRI images, should reflect the
      overall meaningfulness of a set of stimuli for the subject, rather than
      differences among the stimuli. We tested this hypothesis by quantifying the
      differentiation of brain activity patterns in response to a movie sequence, to
      the same movie scrambled in time, and to 'TV noise', where the pixels from each
      movie frame were scrambled in space. While overall cortical activation was strong
      and widespread in all conditions, the differentiation (Lempel-Ziv complexity) of
      brain activation patterns was correlated with the meaningfulness of the stimulus
      set, being highest in the movie condition, intermediate in the scrambled movie
      condition, and minimal for 'TV noise'. Stimulus set meaningfulness was also
      associated with higher information integration among cortical regions. These
      results suggest that the differentiation of neural responses can be used to
      assess the meaningfulness of a given set of stimuli for a given subject, without
      the need to identify the features and categories that are relevant to the
      subject, nor the precise location of selective neural responses.

PMID- 25970445
TI  - Health and human rights in eastern Myanmar after the political transition: a
      population-based assessment using multistaged household cluster sampling.
AB  - BACKGROUND: Myanmar transitioned to a nominally civilian parliamentary government
      in March 2011. Qualitative reports suggest that exposure to violence and
      displacement has declined while international assistance for health services has
      increased. An assessment of the impact of these changes on the health and human
      rights situation has not been published. METHODS AND FINDINGS: Five community
      based organizations conducted household surveys using two-stage cluster sampling
      in five states in eastern Myanmar from July 2013-September 2013. Data was
      collected from 6, 178 households on demographics, mortality, health outcomes,
      water and sanitation, food security and nutrition, malaria, and human rights
      violations (HRV). Among children aged 6-59 months screened, the prevalence of
      global acute malnutrition (representing moderate or severe malnutrition) was
      11.3% (8.0-14.7). A total of 250 deaths occurred during the year prior to the
      survey. Infant deaths accounted for 64 of these (IMR 94.2; 95% CI 66.5-133.5) and
      there were 94 child deaths (U5MR 141.9; 95% CI 94.8-189.0). 10.7% of households
      (95% CI 7.0-14.5) experienced at least one HRV in the past year, while four
      percent reported 2 or more HRVs. Household exposure to one or more HRVs was
      associated with moderate-severe malnutrition among children (14.9 vs. 6.8%;
      prevalence ratio 2.2, 95% CI 1.2-4.2). Household exposure to HRVs was associated
      with self-reported fair or poor health status among respondents (PR 1.3; 95% CI
      1.1-1.5). CONCLUSION: This large survey of health and human rights demonstrates
      that two years after political transition, vulnerable populations of eastern
      Myanmar are less likely to experience human rights violations compared to
      previous surveys. However, access to health services remains constrained, and
      risk of disease and death remains higher than the country as a whole. Efforts to
      address these poor health indicators should prioritize support for populations
      that remain outside the scope of most formal government and donor programs.

PMID- 25970447
TI  - Measuring information transfer in a soft robotic arm.
AB  - Soft robots can exhibit diverse behaviors with simple types of actuation by
      partially outsourcing control to the morphological and material properties of
      their soft bodies, which is made possible by the tight coupling between control,
      body, and environment. In this paper, we present a method that will
      quantitatively characterize these diverse spatiotemporal dynamics of a soft body
      based on the information-theoretic approach. In particular, soft bodies have the
      ability to propagate the effect of actuation through the entire body, with a
      certain time delay, due to their elasticity. Our goal is to capture this delayed
      interaction in a quantitative manner based on a measure called momentary
      information transfer. We extend this measure to soft robotic applications and
      demonstrate its power using a physical soft robotic platform inspired by the
      octopus. Our approach is illustrated in two ways. First, we statistically
      characterize the delayed actuation propagation through the body as a strength of
      information transfer. Second, we capture this information propagation directly as
      local information dynamics. As a result, we show that our approach can
      successfully characterize the spatiotemporal dynamics of the soft robotic
      platform, explicitly visualizing how information transfers through the entire
      body with delays. Further extension scenarios of our approach are discussed for
      soft robotic applications in general. 

PMID- 25970448
TI  - Combinatorial Study of the Li-Ni-Mn-Co Oxide Pseudoquaternary System for Use in
      Li-Ion Battery Materials Research.
AB  - Combinatorial synthesis has proven extremely effective in screening for new
      battery materials for Li-ion battery electrodes. Here, a study in the Li-Ni-Mn-Co
      O system is presented, wherein samples with nearly 800 distinct compositions were
      prepared using a combinatorial and high-throughput method to screen for single
      phase materials of high interest as next generation positive electrode materials.
      X-ray diffraction is used to determine the crystal structure of each sample. The
      Gibbs' pyramid representing the pseudoquaternary system was studied by making
      samples within three distinct pseudoternary planes defined at fractional cobalt
      metal contents of 10%, 20%, and 30% within the Li-Ni-Mn-Co-O system. Two large
      single-phase regions were observed in the system: the layered region (ordered
      rocksalt) and cubic spinel region; both of which are of interest for next
      generation positive electrodes in lithium-ion batteries. These regions were each
      found to stretch over a wide range of compositions within the Li-Ni-Mn-Co-O
      pseudoquaternary system and had complex coexistence regions existing between
      them. The sample cooling rate was found to have a significant effect on the
      position of the phase boundaries of the single-phase regions. The results of this
      work are intended to guide further research by narrowing the composition ranges
      worthy of study and to illustrate the broad range of applications where solution
      based combinatorial synthesis can have significant impact. 

PMID- 25970449
TI  - Thrombin-induced lysosomal exocytosis in human platelets is dependent on
      secondary activation by ADP and regulated by endothelial-derived substances.
AB  - Exocytosis of lysosomal contents from platelets has been speculated to
      participate in clearance of thrombi and vessel wall remodelling. The mechanisms
      that regulate lysosomal exocytosis in platelets are, however, still unclear. The
      aim of this study was to identify the pathways underlying platelet lysosomal
      secretion and elucidate how this process is controlled by platelet inhibitors. We
      found that high concentrations of thrombin induced partial lysosomal exocytosis
      as assessed by analysis of the activity of released N-acetyl-beta-glucosaminidase
      (NAG) and by identifying the fraction of platelets exposing the lysosomal
      associated membrane protein (LAMP)-1 on the cell surface by flow cytometry.
      Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally
      effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in
      response to thrombin was significantly reduced if the secondary activation by ADP
      was inhibited by the P2Y12 antagonist cangrelor, while inhibition of thromboxane
      A2 formation by treatment with acetylsalicylic acid was of minor importance in
      this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine
      (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I2 (PGI2)
      significantly suppressed lysosomal exocytosis. We conclude that platelet
      inhibitors that mimic functional endothelium such as PGI2 or NO efficiently
      counteract lysosomal exocytosis. Furthermore, we suggest that secondary release
      of ADP and concomitant signaling via PAR1/4- and P2Y12 receptors is important for
      efficient platelet lysosomal exocytosis by thrombin. 

PMID- 25970450
TI  - Colorectal cancer.

PMID- 25970446
TI  - Sharing and Specificity of Co-expression Networks across 35 Human Tissues.
AB  - To understand the regulation of tissue-specific gene expression, the GTEx
      Consortium generated RNA-seq expression data for more than thirty distinct human
      tissues. This data provides an opportunity for deriving shared and tissue
      specific gene regulatory networks on the basis of co-expression between genes.
      However, a small number of samples are available for a majority of the tissues,
      and therefore statistical inference of networks in this setting is highly
      underpowered. To address this problem, we infer tissue-specific gene co
      expression networks for 35 tissues in the GTEx dataset using a novel algorithm,
      GNAT, that uses a hierarchy of tissues to share data between related tissues. We
      show that this transfer learning approach increases the accuracy with which
      networks are learned. Analysis of these networks reveals that tissue-specific
      transcription factors are hubs that preferentially connect to genes with tissue
      specific functions. Additionally, we observe that genes with tissue-specific
      functions lie at the peripheries of our networks. We identify numerous modules
      enriched for Gene Ontology functions, and show that modules conserved across
      tissues are especially likely to have functions common to all tissues, while
      modules that are upregulated in a particular tissue are often instrumental to
      tissue-specific function. Finally, we provide a web tool, available at
      mostafavilab.stat.ubc.ca/GNAT, which allows exploration of gene function and
      regulation in a tissue-specific manner. 

PMID- 25970451
TI  - Microbiome: Microbial mystery.

PMID- 25970452
TI  - Drug development: Mix and match.

PMID- 25970453
TI  - Q&A: Hans Clevers. Banking on organoids.

PMID- 25970454
TI  - Colorectal cancer: 5 big questions.

PMID- 25970455
TI  - A disease of growth.

PMID- 25970456
TI  - Screening: Early alert.

PMID- 25970457
TI  - Prevention: Tending the gut.

PMID- 25970458
TI  - Q&A: Victor Velculescu. Out for blood.

PMID- 25970459
TI  - The effect of female quality on male ejaculatory expenditure and reproductive
      success in a praying mantid.
AB  - Strategic ejaculation is a behavioural strategy shown by many animals as a
      response to sperm competition and/or as a potential mechanism of cryptic male
      choice. Males invest more mating resources when the risk of sperm competition
      increases or they invest more in high quality females to maximize their
      reproductive output. We tested this hypothesis in the false garden mantid
      Pseudomantis albofimbriata, where females are capable of multiply mating and body
      condition is an indicator of potential reproductive fitness. We predicted male
      mantids would ejaculate strategically by allocating more sperm to high quality
      females. To determine if and how males alter their ejaculate in response to mate
      quality, we manipulated female food quantity so that females were either in good
      condition with many eggs (i.e. high quality) or poor condition with few eggs
      (i.e. low quality). Half of the females from each treatment were used in mating
      trials in which transferred sperm was counted before fertilisation occurred and
      the other half of females were used in mating trials where fertilisation occurred
      and ootheca mass and total eggs in the ootheca were recorded. Opposed to our
      predictions, the total number of sperm and the proportion of viable sperm
      transferred did not vary significantly between female treatments. Male
      reproductive success was entirely dependent on female quality/fecundity, rather
      than on the number of sperm transferred. These results suggest that female
      quality is not a major factor influencing postcopulatory male mating strategies
      in P. albofimbriata, and that sperm number has little effect on male reproductive
      success in a single mating scenario. 

PMID- 25970460
TI  - Prevalence of periodontitis in an adult population from an urban area in North
      Italy: findings from a cross-sectional population-based epidemiological survey.
AB  - AIM: There is a paucity of up-to-date data regarding prevalence and risk
      indicators of periodontitis in Italy. Therefore, the aim of this study was to
      evaluate the prevalence of periodontitis and its risk indicators among adults
      from an urban area in North Italy. MATERIAL AND METHODS: This cross-sectional
      survey used a stratified two-stage probability sampling method to draw a
      representative sample of the adult population of the city of Turin. About 1600
      individuals, 20-75 years old, were randomly selected and 736 subjects agreed to
      participate (47% of the sampled subjects). Clinical parameters were assessed
      using a full-mouth protocol. Logistic models were applied to assess associations
      between periodontitis and its putative risk indicators. Age was included as
      restricted cubic spline. RESULTS: Based on CDC/AAP case definition, the
      prevalence estimates of severe and moderate periodontitis were 34.94% (95% CI:
      31.23-38.74) and 40.78% (95% CI: 36.89-44.79). The probability of periodontitis
      increased in smokers (adjusted OR 2.06, 95% IC: 1.26-3.37, p = 0.004) and with
      age but leveled off in the 50+ year-old group (p < 0.001). CONCLUSION:
      Periodontitis was highly prevalent in the Turin population. The present data will
      enable development of appropriate public health programs and allocation of
      resources.

PMID- 25970461
TI  - Structural insights into interactions between ubiquitin specific protease 5 and
      its polyubiquitin substrates by mass spectrometry and ion mobility spectrometry.
AB  - Nanoelectrospray ionization-mass spectrometry and ion mobility-mass spectrometry
      have been used to study the interactions of the large, multidomain, and
      conformationally flexible deubiquitinating enzyme ubiquitin specific protease 5
      (USP5) with mono- and poly-ubiquitin (Ub) substrates. Employing a C335A active
      site mutant, mass spectrometry was able to detect the stable and cooperative
      binding of two mono-Ub molecules at the Zinc-finger ubiquitin binding protein
      (ZnF-UBP) and catalytic site domains of USP5. Tetra-ubiquitin, in contrast, bound
      to USP5 with a stoichiometry of 1 : 1, and formed additional interactions with
      USP5's two ubiquitin associated domains (UBAs). Charge-state distribution and ion
      mobility analysis revealed that both mono- and tetra-ubiquitin bound to the
      compact conformation of USP5 only, and that tetra-ubiquitin binding was able to
      shift the conformational distribution of USP5 from a mixture of extended and
      compact forms to a completely compact conformation. 

PMID- 25970462
TI  - PCR-Based Multiple Species Cell Counting for In Vitro Mixed Culture.
AB  - Changes of bacterial profiles in microbial communities are strongly associated
      with human health. There is an increasing need for multiple species research in
      vitro. To avoid high cost or measurement of a limited number of species, PCR
      based multiple species cell counting (PCR-MSCC) has been conceived. Species
      specific sequence is defined as a unique sequence of one species in a multiple
      species mixed culture. This sequence is identified by comparing a random 1000 bp
      genomic sequence of one species with the whole genome sequences of the other
      species in the same artificial mixed culture. If absent in the other genomes, it
      is the species-specific sequence. Species-specific primers were designed based on
      the species-specific sequences. In the present study, ten different oral
      bacterial species were mixed and grown in Brain Heart Infusion Yeast Extract with
      1% sucrose for 24 hours. Biofilm was harvested and processed for DNA extraction
      and q-PCR amplification with the species-specific primers. By comparing the q-PCR
      data of each species in the unknown culture with reference cultures, in which the
      cell number of each species was determined by colony forming units on agar plate,
      the cell number of that strain in the unknown mixed culture was calculated. This
      technique is reliable to count microorganism numbers that are less than 100,000
      fold different from other species within the same culture. Theoretically, it can
      be used in detecting a species in a mixed culture of over 200 species. Currently
      PCR-MSCC is one of the most economic methods for quantifying single species cell
      numbers, especially for the low abundant species, in a multiple artificial mixed
      culture in vitro. 

PMID- 25970463
TI  - An elevated body mass index increases lung volume but reduces airflow in Italian
      schoolchildren.
AB  - BACKGROUND: Asthma and obesity are important and growing health issues worldwide.
      Obesity is considered a risk factor for asthma, due to the induction of changes
      in airway mechanics and altered airway inflammation. METHODS: We cross
      sectionally investigated the effect of increased weight on pulmonary function in
      a large population sample of healthy children, aged 10-17 yrs living in Palermo,
      Italy. Explanatory effect of weight on lung function variables were evaluated by
      multiple linear regression models, taking into account height, gender, and age
      class. RESULTS: Among the 2,393 subjects, FVC and FEV1 were positively correlated
      to weight. Multiple regression models showed that the weight beta coefficient for
      FEV1 was significantly lower with respect to that for FVC (0.005 and 0.009 l/kg,
      respectively), indicating a different magnitude in explanatory effect of weight
      on FVC and FEV1. Both FEV1/FVC and FEF25-75%/FVC ratios were negatively
      correlated to weight, while FEF25-75% was not significantly correlated. Similar
      results were obtained also when 807 symptomatic subjects were introduced in the
      model through a sensitivity analysis. CONCLUSION: In healthy children, the
      disproportionate increase of FEV1 and FVC with weight produces airflow decrease
      and consequently apparent poorer lung function independently from respiratory
      disease status.

PMID- 25970464
TI  - Association of HLA class II alleles with hepatitis C virus clearance and
      persistence in thalassemia patients from Iran.
AB  - There is no published data on association of HLA class II alleles with clearance
      or persistence after acute hepatitis C virus (HCV) infection in patients from
      Iran. HLA DRB1, DQA1, and DQB1 alleles were determined using polymerase chain
      reaction amplification with sequence specific primers (PCR-SSP) on a total of 117
      thalassemia patients (63 with chronic infection, and 54 with viral clearance) and
      120 healthy controls. HLA-DRB1*0301 and DQA1*0501 alleles were found
      significantly present in patients with HCV clearance compared to those with
      chronic infection (P = 0.03 and P = 0.0007, respectively). By contrast,
      DRB1*0701, DQA1*0201, and DQB1*0602 alleles occurred significantly in those with
      chronic infection compared to those with viral clearance (P = 0.004, P = 0.007,
      and P = 0.02, respectively). As compared to the controls, DRB1*0301, DRB1*11,
      DQA1*0501, and DQB1*0301 alleles showed a significant decrease in chronic
      patients (P = 0.002, P = 0.001, P = 0.0001, and P = 0.0004, respectively).
      Furthermore, the haplotype frequencies of DRB1*0301, DQA1*0501, DQB1*0201, and
      DRB1*1101, DQA1*0501, DQB1*0301 were found significantly higher (P = 0.004 and P
      = 0.04, respectively) in patients with HCV clearance than those with chronic
      infection. By contrast, the haplotype DRB1*0701, DQA1*0201, DQB1*0201 occurred
      more frequently (P = 0.02) in those with chronic infection compared with those
      with viral clearance. These findings suggest that particular HLA alleles and
      related haplotypes may have an influence on the outcome of HCV infection among
      the Iranian patients. Some of the HLA alleles found in the Iranian patients are
      different from those reported elsewhere, suggesting that the immunogenetic makeup
      for HCV clearance or persistence may vary based on the ethnicity.

PMID- 25970465
TI  - Physical Demand but Not Dexterity Is Associated with Motor Flexibility during
      Rapid Reaching in Healthy Young Adults.
AB  - Healthy humans are able to place light and heavy objects in small and large
      target locations with remarkable accuracy. Here we examine how dexterity demand
      and physical demand affect flexibility in joint coordination and end-effector
      kinematics when healthy young adults perform an upper extremity reaching task. We
      manipulated dexterity demand by changing target size and physical demand by
      increasing external resistance to reaching. Uncontrolled manifold analysis was
      used to decompose variability in joint coordination patterns into variability
      stabilizing the end-effector and variability de-stabilizing the end-effector
      during reaching. Our results demonstrate a proportional increase in stabilizing
      and de-stabilizing variability without a change in the ratio of the two
      variability components as physical demands increase. We interpret this finding in
      the context of previous studies showing that sensorimotor noise increases with
      increasing physical demands. We propose that the larger de-stabilizing
      variability as a function of physical demand originated from larger sensorimotor
      noise in the neuromuscular system. The larger stabilizing variability with larger
      physical demands is a strategy employed by the neuromuscular system to counter
      the de-stabilizing variability so that performance stability is maintained. Our
      findings have practical implications for improving the effectiveness of movement
      therapy in a wide range of patient groups, maintaining upper extremity function
      in old adults, and for maximizing athletic performance. 

PMID- 25970466
TI  - Longitudinal Sequence and Functional Evolution within Glycoprotein E2 in
      Hepatitis C Virus Genotype 3a Infection.
AB  - The E2 glycoprotein of Hepatitis C virus (HCV) is a major target of the
      neutralizing antibody (NAb) response with the majority of epitopes located within
      its receptor binding domain (RBD; 384-661). Within E2 are three variable regions
      located at the N-terminus (HVR1; 384-411), and internally at 460-480 (HVR2) and
      570-580 [intergenotypic variable region (igVR)], all of which lie outside a
      conserved core domain that contains the CD81 binding site, essential for
      attachment of virions to host cells and a major target of NAbs. In this study, we
      examined the evolution of the E1 and E2 region in two patients infected with
      genotype 3a virus. Whereas one patient was able to clear the acute infection, the
      other developed a chronic infection. Mutations accumulated at multiple positions
      within the N-terminal HVR1 as well as within the igVR in both patients over time,
      whereas mutations in HVR2 were observed only in the chronically infected patient.
      Mutations within or adjacent to the CD81 contact site were observed in both
      patients but were less frequent and more conservative in the patient that cleared
      his/her infection. The evolution of CD81 binding function and antigenicity was
      examined with longitudinal E2 RBD sequences. The ability of the RBD to bind CD81
      was completely lost by week 108 in the patient that developed chronic HCV. In the
      second patient, the ability of the week 36 RBD, just prior to viral clearance, to
      bind CD81 was reduced ~50% relative to RBD sequences obtained earlier. The
      binding of a NAb specific to a conserved epitope located within E2 residues 411
      428 was significantly reduced by week 108 despite complete conservation of its
      epitope suggesting that E2 antigenicity is allosterically modulated. The exposure
      of non-neutralizing antibody epitopes was similarly explored and we observed that
      the epitope of 3 out of 4 non-NAbs were significantly more exposed in the RBDs
      representing the late timepoints in the chronic patient. By contrast, the
      exposure of non-neutralizing epitopes was reduced in the patient that cleared
      his/her infection and could in part be attributed to sequence changes in the
      igVR. These studies reveal that during HCV infection, the exposure of the CD81
      binding site on E2 becomes increasingly occluded, and the antigenicity of the E2
      RBD towards both neutralizing and non-neutralizing antibodies is modulated via
      allosteric mechanisms. 

PMID- 25970468
TI  - Evolutionary Migration of the Disjunct Salt Cress Eutrema salsugineum (=
      Thellungiella salsuginea, Brassicaceae) between Asia and North America.
AB  - Eutrema salsugineum (= Thellungiella salsuginea Brassicaceae), a species growing
      in highly saline habitats, is a good model for use in salt-stress research.
      However, its evolutionary migrations and genetic variations within and between
      disjunct regions from central Asia to northern China and North America remain
      largely unknown. We examined genetic variations and phylogeographic patterns of
      this species by sequencing ITS, 9 chloroplast (cp) DNA fragments (4379 bp) and 10
      unlinked nuclear loci (6510 bp) of 24 populations across its distributional
      range. All markers suggested the high genetic poverty of this species and the
      limited number of genetic variations recovered was congruently partitioned
      between central Asia, northern China and North America. Further modelling of
      nuclear population-genetic data based on approximate bayesian computation (ABC)
      analyses indicated that the long-distance dispersals after the recent origin of
      E. salsugineum may have occurred from central Asia to the other two regions
      respectively within 20000 years. The fast demographic expansions should have
      occurred in northern China in a more recent past. Our study highlights the
      importance of using ABC analyses and nuclear population genetic data to trace
      evolutionary migrations of the disjunct distributions of the plants in the recent
      past. 

PMID- 25970469
TI  - Bamboo Leaf Flavones and Tea Polyphenols Show a Lipid-lowering Effect in a Rat
      Model of Hyperlipidemia.
AB  - At present, most of the lipid-lowering drugs are western medicines, which have a
      lot of adverse reactions. Zhucha, an age-old Uyghur medicine, is made up of
      bamboo leaves and tea (green tea), which has good efficacy and lipid-lowering
      effect. The purpose of this study was to undertake a pharmacodynamic examination
      of the optimal proportions of bamboo leaf flavones and tea polyphenols required
      to achieve lipid lowering in rats. A hyperlipidemia rat model was used to examine
      the lipid lowering effects of bamboo leaf flavones and tea polyphenols. Wistar
      rats were divided into 13 groups including one hyperlipidemia model group and 2
      positive drug groups as well as experimental groups (9 groups dosed with
      different proportions of bamboo leaf flavones and tea polyphenols, the 3 dosages
      of bamboo leaf flavones were 75 mg/kg/d, 50 mg/kg/d and 25 mg/kg/d respectively,
      the 3 dosages of tea polyphenol were 750 mg/kg/d, 500 mg/kg/d and 250 mg/kg/d).
      The weight, the levels of triglyceride (TG) and high-density lipoprotein
      cholesterol (HDL) were determined. A high dose of bamboo leaf flavones (75
      mg/kg/d) combined with a medium dose of tea polyphenols (500 mg/kg/d) was deemed
      to be optimal for achieving a lipid-lowering effect, the weight had the smallest
      increase and the level of TG and HDL was similar to positive control. The bamboo
      leaf flavones and tea polyphenols were mixed according to a certain proportion
      (1:6.7), and the mixture achieved a lipid-lowering effect and might prove to be
      useful as a natural lipid-lowering agent. 

PMID- 25970467
TI  - Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the
      regulation of human androgen biosynthesis.
AB  - Androgens are essential for sexual development and reproduction. However,
      androgen regulation in health and disease is poorly understood. We showed that
      human adrenocortical H295R cells grown under starvation conditions acquire a
      hyperandrogenic steroid profile with changes in steroid metabolizing enzymes
      HSD3B2 and CYP17A1 essential for androgen production. Here we studied the
      regulatory mechanisms underlying androgen production in starved H295R cells.
      Microarray expression profiling of normal versus starved H295R cells revealed
      fourteen differentially expressed genes; HSD3B2, HSD3B1, CYP21A2, RARB, ASS1,
      CFI, ASCL1 and ENC1 play a role in steroid and energy metabolism and ANGPTL1,
      PLK2, DUSP6, DUSP10 and FREM2 are involved in signal transduction. We discovered
      two new gene networks around RARB and ANGPTL1, and show how they regulate
      androgen biosynthesis. Transcription factor RARB stimulated the promoters of
      genes involved in androgen production (StAR, CYP17A1 and HSD3B2) and enhanced
      androstenedione production. For HSD3B2 regulation RARB worked in cooperation with
      Nur77. Secretory protein ANGPTL1 modulated CYP17A1 and DUSP6 expression by
      inducing ERK1/2 phosphorylation. By contrast, our studies revealed no evidence
      for hormones or cell cycle involvement in regulating androgen biosynthesis. In
      summary, these studies establish a firm role for RARB and ANGPTL1 in the
      regulation of androgen production in H295R cells. 

PMID- 25970470
TI  - Declaration of ALMA-ATA.

PMID- 25970476
TI  - Zenk et al. Respond.

PMID- 25970477
TI  - Erratum.

PMID- 25970478
TI  - Prevalence of amyotrophic lateral sclerosis - United States, 2010-2011.

PMID- 25970479
TI  - Quasi-combinatorial energy landscapes for nanoalloy structure optimisation.
AB  - We formulate nanoalloy structure prediction as a mixed-variable optimisation
      problem, where the homotops can be associated with an effective, quasi
      combinatorial energy landscape in permutation space. We survey this effective
      landscape for a representative set of binary systems modelled by the Gupta
      potential. In segregating systems with small lattice mismatch, we find that
      homotops have a relatively straightforward landscape with few local optima - a
      scenario well-suited for local (combinatorial) optimisation techniques that scale
      quadratically with system size. Combining these techniques with multiple local
      neighbourhood structures yields a search for multiminima, and we demonstrate that
      generalised basin-hopping with a metropolis acceptance criterion in the space of
      multiminima can then be effective for global optimisation of binary and ternary
      nanoalloys. 

PMID- 25970480
TI  - Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.
AB  - Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive
      target for anticancer therapy in 2003, the search for inhibitors has been
      intensely pursued both in academia and in pharmaceutical companies. Many novel
      IDO1 inhibitor scaffolds have been described, and a few potent compounds have
      entered clinical trials. However, a significant number of the reported compounds
      contain problematic functional groups, suggesting that enzyme inhibition could be
      the result of undesirable side reactions instead of selective binding to IDO1.
      Here, we describe issues in the employed experimental protocols, review and
      classify reported IDO1 inhibitors, and suggest different approaches for
      confirming viable inhibitor scaffolds. 

PMID- 25970482
TI  - Correction: Yersinia pestis Activates Both IL-1beta and IL-1 Receptor Antagonist
      to Modulate Lung Inflammation during Pneumonic Plague.

PMID- 25970481
TI  - Glycopeptidolipid of Mycobacterium smegmatis J15cs Affects Morphology and
      Survival in Host Cells.
AB  - Mycobacterium smegmatis has been widely used as a mycobacterial infection model.
      Unlike the M. smegmatis mc(2)155 strain, M. smegmatis J15cs strain has the
      advantage of surviving for one week in murine macrophages. In our previous
      report, we clarified that the J15cs strain has deleted apolar glycopeptidolipids
      (GPLs) in the cell wall, which may affect its morphology and survival in host
      cells. In this study, the gene causing the GPL deletion in the J15cs strain was
      identified. The mps1-2 gene (MSMEG_0400-0402) correlated with GPL biosynthesis.
      The J15cs strain had 18 bps deleted in the mps1 gene compared to that of the
      mc(2)155 strain. The mps1-complemented J15cs mutant restored the expression of
      GPLs. Although the J15cs strain produces a rough and dry colony, the colony
      morphology of this mps1-complement was smooth like the mc(2)155 strain. The
      length in the mps1-complemented J15cs mutant was shortened by the expression of
      GPLs. In addition, the GPL-restored J15cs mutant did not survive as long as the
      parent J15cs strain in the murine macrophage cell line J774.1 cells. The results
      are direct evidence that the deletion of GPLs in the J15cs strain affects
      bacterial size, morphology, and survival in host cells.

PMID- 25970483
TI  - The first description of dominance hierarchy in captive giraffe: not loose and
      egalitarian, but clear and linear.
AB  - Wild giraffes live in extensive groups in the fission fusion system, maintaining
      long social distances and loose social bonds. Within these groups, resources are
      widely distributed, agonistic encounters are scarce and the dominance hierarchy
      was reported in males only, while never deeply analysed. In captivity, the
      possibility to maintain inter-individual distances is limited and part of the
      resources is not evenly distributed. Consequently, we suggest that agonistic
      encounters should be more frequent, leading to the establishment of the dominance
      hierarchy. Based on the differences in resource-holding potential, we suggested
      that the rank of an individual would be affected by age and sex. Based on
      hypotheses of prior ownership, we tested whether rank was positively affected by
      the time spent in a herd and whether it was stable in adult females, which were
      present long-term in the same herd. We originally monitored four herds of
      Rothschild giraffes (Giraffa camelopardalis rothschildii) in Dvur Kralove zoo (n
      = 8), Liberec zoo (n = 6), and two herds in Prague zoo: Prague 1 (n = 8) and
      Prague 2 (n = 9). The Prague 1 and Prague 2 herds were then combined and the
      resulting fifth herd was observed over three consecutive years (2009, 2010, and
      2011) (n = 14, 13, and 14, respectively). We revealed a significantly linear
      hierarchy in Dvur Kralove, Prague 2 and in the combined herd in Prague. Rank was
      significantly affected by age in all herds; older individuals dominated the
      younger ones. In females, rank was positively affected by the time spent in the
      herd and adult females in Prague maintained their rank during three consecutive
      years. This study represents the first analysis of the dominance hierarchy in the
      captive giraffe, and discusses the behavioural flexibility of the social
      structure in response to monopolisable resources in a captive environment. 

PMID- 25970484
TI  - Retinal Development and Ommin Pigment in the Cranchiid Squid Teuthowenia
      pellucida (Cephalopoda: Oegopsida).
AB  - The cranchiid Teuthowenia pellucida, like many deep-sea squid species, possesses
      large eyes that maximise light sensitivity in a nearly aphotic environment. To
      assess ontogenetic changes in the visual system, we conducted morphometric and
      histological analyses of the eyes using specimens from New Zealand collections.
      While the ratio between eye diameter and mantle length maintained a linear
      relationship throughout development, histological sections of the retina revealed
      that the outer photoreceptor layer became proportionally longer as the animal
      aged, coincident with a habitat shift into deeper, darker ocean strata. Other
      retinal layers maintained the same absolute thickness as was observed in
      paralarvae. Granules of the pigment ommin, normally located in the screening
      layer positioned at the base of the photoreceptors, were also observed at the
      outer end of the photoreceptor segments throughout the retina in young and mid
      sized specimens. Early developmental stages of this species, dwelling in shallow
      waters, may therefore rely on migratory ommin to help shield photoreceptors from
      excess light and prevent over-stimulation. The oldest, deeper-dwelling specimens
      of T. pellucida examined had longer photoreceptors, and little or no migrated
      ommin was observed; we suggest therefore that short-term adaptive mechanisms for
      bright light conditions may be used primarily during epipelagic, early life
      stages in this species. 

PMID- 25970486
TI  - Synthesis and characterization of group 4 metal alkoxide complexes containing
      imine based bis-bidentate ligands: effective catalysts for the ring opening
      polymerization of lactides, epoxides and polymerization of ethylene.
AB  - A series of Ti(iv), Zr(iv) and Hf(iv) complexes containing imine based bis
      bidentate ligands were synthesized and characterized by various spectroscopic
      techniques, elemental analysis and X-ray crystallography. The ligands m-xysal
      ((t)Bu)4 (L(1)((t)Bu)4), m-xysal-(Me)2((t)Bu)2 (L(2)Me2((t)Bu)2) and m-xysal
      (Cl)4 (L(3)Cl4) were reacted with Ti(O(i)Pr)4, Zr(O(i)Pr)4.(i)PrOH and
      Hf(O(t)Bu)4 in a 1 : 1 stoichiometric ratio to form complexes (L2M2(OR)4, where L
      = m-xysal-((t)Bu)4, m-xysal-(Me)2((t)Bu)2 and m-xysal-(Cl)4, M = Ti and R =
      (i)Pr, (L2M2(OR)4, where L = m-xysal-((t)Bu)4, m-xysal-(Me)2((t)Bu)2 and m-xysal
      (Cl)4, M = Zr and R = (i)Pr and (L3M3(OR)6, where L = m-xysal-((t)Bu)4, m-xysal
      (Me)2((t)Bu)2 and m-xysal-(Cl)4, M = Hf and R = (t)Bu respectively. Complex was
      crystallized from a 1 : 1 : 1 mixture of chloroform, ethanol and toluene to yield
      an ethoxy substituted complex (L2M2(OR)4, L = m-xysal-(Me)2((t)Bu)2, M = Zr and R
      = Et. The X-ray structures of , and illustrate that and are binuclear helical
      complexes, whereas is trinuclear. These complexes were found to be active for the
      ring opening polymerization (ROP) of lactides (rac-LA, l-LA) and epoxides. All
      the complexes produced atactic poly(lactic acid) (PLA) with good number average
      molecular weight (Mn) and narrow molecular weight distributions (MWDs). The
      magnetic isotropic shielding constants were calculated using the
      GIAO/B3LYP/LANL2DZ approach and correlated with the experimental values. The HOMO
      LUMO energy band gaps and Mulliken charges were calculated using the DFT method
      to explain the reactivity of these complexes according to the relationship
      between chemical hardness and reactivity established by Pearson. In addition,
      complexes , activated by methylaluminoxane (MAO), were used and found to be
      moderately active for ethylene polymerization. 

PMID- 25970485
TI  - Combined use of hyperbaric and hypobaric ropivacaine significantly improves
      hemodynamic characteristics in spinal anesthesia for caesarean section: a
      prospective, double-blind, randomized, controlled study.
AB  - PURPOSE: To observe the hemodynamic changes of parturients in the combined use of
      hyperbaric (4 mg) and hypobaric (6 mg) ropivacaine during spinal anesthesia for
      caesarean section in this randomized double-blind study. METHODS: Parturients (n
      = 136) undergoing elective cesarean delivery were randomly and equally allocated
      to receive either combined hyperbaric and hypobaric ropivacaine (Group A) or
      hyperbaric ropivacaine (Group B). Outcome measures were: hemodynamic
      characteristics, maximum height of sensory block, time to achieve T8 sensory
      blockade level, incidence of complications, Apgar scores at 1 and 5 min, and
      neonatal blood gas analysis. RESULTS: Group A had a lower level of sensory
      blockade (T6 [T6-T7]) and longer time to achieve T8 sensory blockade level (8 +/-
      1.3 min) than did patients in Group B (T3 [T2-T4] and 5 +/- 1.0 min,
      respectively; P < 0.001, both). The incidence rates for hypotension, nausea, and
      vomiting were significantly lower in Group A (13%, 10%, and 3%, respectively)
      than Group B (66%, 31%, and 13%; P < 0.001, P = 0.003, P = 0.028). CONCLUSIONS:
      Combined use of hyperbaric (4 mg) and hypobaric (6 mg) ropivacaine significantly
      decreased the incidences of hypotension and complications in spinal anesthesia
      for caesarean section by extending induction time and decreasing the level of
      sensory blockade. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-TRC
      13004622.

PMID- 25970487
TI  - Comparison Stratagems of Post-Screening Management of Anti-HCV-Positive Community
      Residents: Simple Notification, Active Referral, or Accessible Medical Care.
AB  - To elucidate the results of post-screening care stratagems for anti-hepatitis C
      virus (HCV)-positive subjects in the community. Part I methods: The intervention
      program: A total of 151,790 subjects underwent a large-scale healthcare
      screening. Subjects aged less than 65 years, with anti-HCV-positive and alanine
      aminotransferase (ALT) level more than 80 IU/L were followed-up to answer a
      structured questionnaire. Those responders who met the reimbursement criteria of
      Taiwan's National Health Insurance for anti-HCV treatment were referred for
      treatment. Part II: The accessible medical care program: In Yujing township, 271
      HCV residents who have been screened before were invited to a bi-weekly hepatitis
      clinic in Yujing health center. Part-I results: A total of 907 anti-HCV-positive
      subjects responded and 197(21.7%) were advised the treatment, but only 83(9.2%)
      did. Finally, 47 patients achieved a sustained virological response (SVR). After
      this intervention program, 96(10.6%) additional patients were encouraged to be
      referred, 33(3.6%) received treatment and 20 obtained a SVR. Part II: A total of
      140(51.7%) subjects responded and 112 were anti-HCV-positive including 31(27.7%)
      HCV RNA-negative, 49(43.8%) HCV RNA-positive plus ALT less than 40 IU/L and
      32(28.5%) HCV RNA-positive plus ALT more than 40 IU/L. During the follow-up, 14
      of 49 patients had ALT more than 40 IU/L. Among 46 eligible HCV patients,
      15(32.6%) received treatment and 10 achieved a SVR. Simple notification only made
      9.2% of the screened HCV patients treat. Active referral could encourage
      additional 3.6% to be treated. Additionally, accessible medical care program
      could result in treatment of 32.6% elderly eligible patients. 

PMID- 25970488
TI  - Docosahexaenoic Acid Downregulates EGF-Induced Urokinase Plasminogen Activator
      and Matrix Metalloproteinase 9 Expression by Inactivating EGFR/ErbB2 Signaling in
      SK-BR3 Breast Cancer Cells.
AB  - Urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) play
      crucial roles in tumor metastasis. Despite the well-known anticancer role of
      docosa-hexaenoic acid (DHA), its specific effect on ErbB2-mediated breast cancer
      metastasis is not fully clarified. In this study, we investigated the effect of
      DHA on epidermal growth factor (EGF)-induced uPA and MMP-9 activity, expression
      and cell invasion in SK-BR3 breast cancer cells and the possible mechanisms
      involved. The results showed that EGF (40 ng/ml) induced uPA and MMP-9 mRNA and
      protein expression, enzyme activity, and 100 MUM DHA significantly inhibited EGF
      induced uPA and MMP-9 mRNA, protein expression, enzyme activity, cell migration,
      and cell invasion. EGF increased protein expression and phosphorylation of EGF
      receptor (EGFR) and ErbB2 as well as of JNK2, ERK1/2, and Akt, and these changes
      were attenuated by DHA pretreatment. AG1478, an inhibitor of EGFR, also
      attenuated EGF-induced activation of EGFR, JNK2, ERK1/2, and Akt. Knocked down
      ErbB2 expression resulted in a similar inhibition of uPA and MMP-9 expression as
      noted by DHA and AG1478. Taken together, these results suggest that suppression
      of EGF-induced metastasis by DHA is likely through an inhibition of EGFR and
      ErbB2 protein expression and the downstream target uPA and MMP-9 activation in SK
      BR3 human breast cancer cells. 

PMID- 25970490
TI  - Impact of Strength Training on Bone Mineral Density in Patients Infected With HIV
      Exhibiting Lipodystrophy.
AB  - This study aimed to evaluate the impact of strength training on bone mineral
      density (BMD) in individuals harboring HIV exhibiting lipodystrophy. The study
      included 20 subjects (16 men) aged 50.60 +/- 6.40 years with reduced BMD,
      presenting positive serology for HIV, using highly active antiretroviral therapy,
      and performing no regular practice of physical exercise before being enrolled in
      the study. Bone mineral density levels were evaluated by dual-energy x-ray
      absorptiometry in the lumbar spine, femoral neck, and 1/3 radius, before and
      after 36 sessions (12 weeks) of strength training. Compared with pre-exercise
      period, the results showed increased BMD in lumbar spine (3.28%; p = 0.012),
      femoral neck (8.45%; p = 0.044), and 1/3 radius (5.41%; p = 0.035). This is the
      first study evaluating the impact of strength training in patients living with
      HIV and exhibiting lipodystrophy, showing an increased BMD in all the regions
      measured (lumbar spine, femoral neck, and 1/3 radius). This study showed the
      beneficial impact of the strength training on BMD increase in patients living
      with HIV as an effective and available approach to improve bone health.

PMID- 25970491
TI  - Faster Heart Rate Recovery With Increased RPE: Paradoxical Responses After an 87
      km Ultramarathon.
AB  - The aim of this study was to determine the relationship between heart rate
      recovery (HRR) and an acute training "overload" by comparing HRR responses before
      and after an ultramarathon road race. Ten runners completed a standardized
      laboratory protocol ~7 days before and between 2 and 4 days after participating
      in the 87-km Comrades Marathon. The protocol included muscle pain ratings, a 5
      bound test, and 20 minutes of treadmill exercise at 70% of maximal oxygen uptake
      followed by 15 minutes of recovery. Respiratory gases and heart rate measurements
      were used to calculate steady-state exercise responses, HRR, and excess
      postexercise oxygen consumption (EPOC), and participants also provided a rating
      of perceived exertion (RPE) during exercise. The RPE was significantly increased
      (13 +/- 2 vs. 11 +/- 1) (p < 0.01), and HRR was significantly faster (35 +/- 5
      beats vs. 29 +/- 4 beats) (p < 0.01) following the postrace vs. prerace
      submaximal exercise bout, with no significant changes in respiratory or heart
      rate parameters during exercise or in EPOC. Although previous studies have shown
      that faster HRR reflected an "adapted" state with enhanced training status, the
      current findings suggest that this may not always be the case. It follows that
      changes in HRR should be considered in the context of other factors, such as
      recent training load and RPE during submaximal exercise.

PMID- 25970489
TI  - Mechanisms of left-right coordination in mammalian locomotor pattern generation
      circuits: a mathematical modeling view.
AB  - The locomotor gait in limbed animals is defined by the left-right leg
      coordination and locomotor speed. Coordination between left and right neural
      activities in the spinal cord controlling left and right legs is provided by
      commissural interneurons (CINs). Several CIN types have been genetically
      identified, including the excitatory V3 and excitatory and inhibitory V0 types.
      Recent studies demonstrated that genetic elimination of all V0 CINs caused
      switching from a normal left-right alternating activity to a left-right
      synchronized "hopping" pattern. Furthermore, ablation of only the inhibitory V0
      CINs (V0D subtype) resulted in a lack of left-right alternation at low locomotor
      frequencies and retaining this alternation at high frequencies, whereas selective
      ablation of the excitatory V0 neurons (V0V subtype) maintained the left-right
      alternation at low frequencies and switched to a hopping pattern at high
      frequencies. To analyze these findings, we developed a simplified mathematical
      model of neural circuits consisting of four pacemaker neurons representing left
      and right, flexor and extensor rhythm-generating centers interacting via
      commissural pathways representing V3, V0D, and V0V CINs. The locomotor frequency
      was controlled by a parameter defining the excitation of neurons and commissural
      pathways mimicking the effects of N-methyl-D-aspartate on locomotor frequency in
      isolated rodent spinal cord preparations. The model demonstrated a typical left
      right alternating pattern under control conditions, switching to a hopping
      activity at any frequency after removing both V0 connections, a synchronized
      pattern at low frequencies with alternation at high frequencies after removing
      only V0D connections, and an alternating pattern at low frequencies with hopping
      at high frequencies after removing only V0V connections. We used bifurcation
      theory and fast-slow decomposition methods to analyze network behavior in the
      above regimes and transitions between them. The model reproduced, and suggested
      explanation for, a series of experimental phenomena and generated predictions
      available for experimental testing. 

PMID- 25970492
TI  - Revisiting the Force-Joint Angle Relationship After Eccentric Exercise.
AB  - The purpose of this study was to evaluate force-angle curve fitting techniques
      pre-eccentric exercise, quantify changes in curve characteristics postexercise,
      and examine the relationship between curve changes and markers of muscle damage.
      Fourteen males unaccustomed to eccentric exercise performed 60 eccentric muscle
      actions of the elbow flexors. Maximal voluntary isometric force was measured
      throughout a range of angles pre- (Pre1 and Pre2), immediately post (IP), and 1,
      2, 4, and 7 days postexercise. Force-angle curves for each visit were constructed
      using second-order polynomials. Changes in curve characteristics (optimal angle,
      peak force, curve height), range of motion, soreness, and creatine kinase
      activity were quantified. Optimal joint angle and force at optimal angle were
      significantly correlated from Pre1 to Pre2 (ICC = 0.821 and 0.979, respectively).
      Optimal angle was significantly right shifted (p = 0.035) by 10.4 +/- 12.9
      degrees  from Pre2 to IP and was restored by 1 day post exercise. Interestingly,
      the r value for curve fit was significantly decreased (p < 0.001) from Pre2 (r =
      0.896) to IP (r = 0.802) and 1 day post exercise (r = 0.750). Curve height was
      significantly decreased (39%) IP and restored to pre-exercise height by 4 days
      postexercise. There was no correlation between optimal angle or curve height and
      other damage markers. In conclusion, force-angle relationships can be accurately
      described using second-order polynomials. After eccentric exercise, the force
      angle curve is flattened and shifted (downward and rightward), but these changes
      are not correlated to other markers of muscle damage. Changes in the force-angle
      relationship are multifaceted, but determining the physiological significance of
      these changes requires further investigation.

PMID- 25970493
TI  - Effect of Traditional vs. Modified Bent-Knee Sit-Up on Abdominal and Hip Flexor
      Muscle Electromyographic Activity.
AB  - The traditional sit-up may be a poor choice for core strength training due to its
      focus on hip flexion. The purpose of this study was to determine differences in
      abdominal and hip flexor muscle activation and trunk and hip kinematics between
      the traditional U.S. Army sit-up and a modified sit-up focusing on trunk flexion.
      Eighteen trained males performed 30 seconds of repetitions of each sit-up style,
      while muscle activation of the rectus abdominis (RA), external oblique (EO), and
      rectus femoris (RF) was recorded using electromyography (EMG). Trunk and hip
      kinematics were measured using 2-D videography. Maximum and mean muscle
      activation, integrated EMG (iEMG), and trunk and hip flexion were compared using
      a repeated-measures design. Maximum EMG of the RF and EO and mean EMG and iEMG of
      the RF were greater during the traditional sit-up. In contrast, mean EMG and iEMG
      of the RA and EO were greater during the modified sit-up. Peak trunk flexion was
      greater during the modified sit-up, and peak hip flexion was greater during the
      traditional sit-up. The greater RF EMG activity and peak hip flexion during the
      traditional sit-up suggest a greater emphasis on hip flexion during this sit-up
      style, which may result in lumbar hyperextension. The greater RA and EO activity
      and peak trunk flexion during the modified sit-up suggest a greater emphasis on
      trunk flexion during this exercise, which may decrease the lumbar spine load.
      Therefore, the modified sit-up may be a better exercise selection to train the
      abdominal muscles.

PMID- 25970494
TI  - Physiological and Movement Demands of Rugby League Referees: Influence on Penalty
      Accuracy.
AB  - Research into the physiological and movement demands of Rugby League (RL)
      referees is limited, with only 1 study in the European Super League (SL). To
      date, no studies have considered decision making in RL referees. The purpose of
      this study was to quantify penalty accuracy scores of RL referees and to
      determine the relationship between penalty accuracy and total distance covered
      (TD), high-intensity running (HIR), and heart rate per 10-minute period of match
      play. Time motion analysis was undertaken on 8 referees over 148 European SL
      games during the 2012 season using 10-Hz global positioning system analysis and
      heart rate monitors. The number and timing of penalties awarded was quantified
      using Opta Stats. Referees awarded the correct decision on 74 +/- 5% of
      occasions. Lowest accuracy was observed in the last 10-minute period of the game
      (67 +/- 13%), with a moderate drop (effect size = 0.86) in accuracy observed
      between 60-70 minutes and 70-80 minutes. Despite this, there were only small
      correlations observed between mean heart rate, TD, HIR efforts, and penalty
      accuracy. Although a moderate correlation was observed between maximum velocity
      and accuracy. Despite only small correlations observed, it would be rash to
      assume that physiological and movement demands of refereeing have no influence on
      decision making. More likely, other confounding variables influence referee
      decision-making accuracy, requiring further investigation. Findings can be used
      by referees and coaches to inform training protocols, ensuring training is
      specific to both cognitive and physical match demands.

PMID- 25970495
TI  - Rhabdomyolysis After Out-of-Water Exercise in an Elite Adolescent Water Polo
      Player Carrying the IL-6 174C Allele Single-Nucleotide Polymorphism.
AB  - We present an adolescent elite water polo player who despite a genetic
      predisposition to develop exercise-induced severe muscle damage due to carrying
      the IL-6 174C allele single-nucleotide polymorphism, developed acute
      rhabdomyolysis only after a vigorous out-of-water training, suggesting that water
      polo training may be more suitable for genetically predisposed athletes.

PMID- 25970496
TI  - Physiological Responses to High-Intensity Interval Exercise Differing in Interval
      Duration.
AB  - We determined the oxygen uptake (V[Combining Dot Above]O2), heart rate (HR), and
      blood lactate responses to 2 high-intensity interval exercise protocols differing
      in interval length. On separate days, 14 recreationally active males performed a
      4 * 4 (four 4-minute intervals at 90-95% HRpeak, separated by 3-minute recovery
      at 50 W) and 16 * 1 (sixteen 1-minute intervals at 90-95% HRpeak, separated by 1
      minute recovery at 50 W) protocol on a cycle ergometer. The 4 * 4 elicited a
      higher mean V[Combining Dot Above]O2 (2.44 +/- 0.4 vs. 2.36 +/- 0.4 L.min) and
      "peak" V[Combining Dot Above]O2 (90-99% vs. 76-85% V[Combining Dot Above]O2peak)
      and HR (95-98% HRpeak vs. 81-95% HRpeak) during the high-intensity intervals.
      Average power maintained was higher for the 16 * 1 (241 +/- 45 vs. 204 +/- 37 W),
      and recovery interval V[Combining Dot Above]O2 and HR were higher during the 16 *
      1. No differences were observed for blood lactate concentrations at the midpoint
      (12.1 +/- 2.2 vs. 10.8 +/- 3.1 mmol.L) and end (10.6 +/- 1.5 vs. 10.6 +/- 2.4
      mmol.L) of the protocols or ratings of perceived exertion (7.0 +/- 1.6 vs. 7.0 +/
      1.4) and Physical Activity Enjoyment Scale scores (91 +/- 15 vs. 93 +/- 12).
      Despite a 4-fold difference in interval duration that produced greater between
      interval transitions in V[Combining Dot Above]O2 and HR and slightly higher mean
      V[Combining Dot Above]O2 during the 4 * 4, mean HR during each protocol was the
      same, and both protocols were rated similarly for perceived exertion and
      enjoyment. The major difference was that power output had to be reduced during
      the 4 * 4 protocol to maintain the desired HR.

PMID- 25970497
TI  - Development of a Noncontact Kickboxing Circuit Training Protocol That Simulates
      Elite Male Kickboxing Competition.
AB  - The aim of this study was to verify whether the specific kickboxing circuit
      training protocol (SKCTP) could reproduce kickboxing combat's hormonal,
      physiological, and physical responses. Twenty athletes of regional and national
      level volunteered to participate in the study (mean +/- SD, age: 21.3 +/- 2.7
      years; height: 170 +/- 0.5 cm; body mass: 73.9 +/- 13.9 kg). After
      familiarization, SKCTP was conducted 1 week before a kickboxing competition.
      Cortisol, testosterone, growth hormone (GH), blood lactate [La], and glucose
      concentrations, as well as the Wingate upper-body test and countermovement jump
      (CMJ) performances were measured before and after SKCTP and combat. Heart rate
      (HR) and rating of perceived exertion (RPE) were measured throughout rounds (R)
      R1, R2, and R3. Testosterone, GH, glucose, [La], HR, RPE, and CMJ did not differ
      among the 2 conditions (p > 0.05). However, Cortisol was higher for competition
      (p = 0.038), whereas both peak (p = 0.003) and mean power (p < 0.001) were higher
      in SKCTP. The study suggests that SKCTP replicates the hormonal, physiological,
      and physical aspects of competition. It is therefore suggested as a good form of
      specific kickboxing training, as well as a specific assessment tool to be used by
      kickboxing coaches to quantify kickboxers' fitness levels, when physiological
      parameters responses to the test are measured.

PMID- 25970498
TI  - Hierarchical Co3O4/Co(OH)2 Nanoflakes as a Supercapacitor Electrode: Experimental
      and Semi-Empirical Model.
AB  - In this research, facile and low cost synthesis methods, electrodeposition at
      constant current density and anodization at various applied voltages, were used
      to produce hierarchical cobalt oxide/hydroxide nanoflakes on top of porous
      anodized cobalt layer. The maximum electrochemical capacitance of 601 mF cm(-2)
      at scan rate of 2 mV s(-1) was achieved for 30 V optimized anodization applied
      voltage with high stability. Morphology and surface chemical composition were
      determined by scanning electron microscopy (SEM) and X-ray photoelectron
      spectroscopy (XPS) analysis. The size, thickness, and density of nanoflakes, as
      well as length of the porous anodized Co layer were measured about 460+/-45 nm,
      52+/-5 nm, 22+/-3 MUm(-2), and 3.4+/-0.3 MUm for the optimized anodization
      voltage, respectively. Moreover, the effect of anodization voltage on the
      resulting supercapacitance was modeled by using the Butler-Volmer formalism. The
      behavior of the modeled capacitance in different anodization voltages was in good
      agreement with the measured experimental data, and it was found that the role and
      contribution of the porous morphology was more decisive than structure of
      nanoflakes in the supercapacitance application.

PMID- 25970499
TI  - Origin of Enhanced Hole Injection in Organic Light-Emitting Diodes with an
      Electron-Acceptor Doping Layer: p-Type Doping or Interfacial Diffusion?
AB  - The electrical doping nature of a strong electron acceptor, 1,4,5,8,9,11
      hexaazatriphenylene hexacarbonitrile (HATCN), is investigated by doping it in a
      typical hole-transport material, N,N'-bis(naphthalen-1-yl)-N,N'-diphenylbenzidine
      (NPB). A better device performance of organic light-emitting diodes (OLEDs) was
      achieved by doping NPB with HATCN. The improved performance could, in principle,
      arise from a p-type doping effect in the codeposited thin films. However,
      physical characteristics evaluations including UV-vis absorption, Fourier
      transform infrared absorption, and X-ray photoelectron spectroscopy demonstrated
      that there was no obvious evidence of charge transfer in the NPB:HATCN composite.
      The performance improvement in NPB:HATCN-based OLEDs is mainly attributed to an
      interfacial modification effect owing to the diffusion of HATCN small molecules.
      The interfacial diffusion effect of the HATCN molecules was verified by the in
      situ ultraviolet photoelectron spectroscopy evaluations. 

PMID- 25970500
TI  - Formation of Pt decorated Ni-Pt nanocubes through low temperature atomic
      diffusion--time-resolved elemental analysis of nanoparticle formation.
AB  - The formation process of Pt decorated Ni-Pt nanocubes was investigated by
      analysing the elemental distribution of Ni and Pt in the particles obtained from
      time-resolved in situ sampling during the synthesis in the oleylamine-1-heptanol
      system. The analysis confirmed the formation of Pt(core)-Ni(shell) nanoparticles
      at the initial stages of the reaction. However, as the reaction time progressed,
      the Pt atoms at the centre diffused outward and reached the corners and edges of
      the particle, whose shape changed from nearly spherical at the initial stages of
      the reaction to a perfect cube at the end of the reaction, forming a Ni rich cube
      (core)-Pt(cage). The cage obtained by dissolving the Ni rich cube was composed
      mainly of Pt and the Ni content in the frame was a mere 12%. The catalytic
      activity of the Pt cage was measured using cyclic voltammetry. The initial
      measurements suggested that the activity was comparable to some of the
      commercially available Pt catalysts. 

PMID- 25970501
TI  - The range of bioinclusions and pseudoinclusions preserved in a new Turonian (~90
      ma) amber occurrence from Southern Australia.
AB  - A new Turonian amber occurrence, representing the oldest in situ amber locality
      in Australia and the southern-most locality in Gondwana, has recently been
      discovered in the Otway Basin of Victoria. The amber was collected from petroleum
      cores and many pieces contain a range of inclusions that can provide information
      on the depositional history of the resin. To date, one species of fern spore
      (Cyathidites minor) and one species of lycophyte spore (Kraeuselisporites sp?)
      have been conclusively identified in the amber, along with filamentous
      microorganisms and degraded plant matter. Several samples are also rife with
      pseudoinclusions as reported recently in other ambers. The abundance of preserved
      particulate debris and wind dispersed spores suggest that the Otway amber formed
      subaerially. Furthermore, based on the range of bioinclusions and forms of
      pseudoinclusions preserved within a single piece of amber, the locus of hardening
      for individual samples is variably interpreted as occurring in the tree tops, on
      the tree trunk or on the ground surface. Notably, specific inclusion assemblages
      are associated with certain colours of amber. By extension, and in accordance
      with recent studies, amber colour may be indicative of depositional environment.
      Variation in the environment of solidification may, therefore, be sufficient to
      account for the broad range of morphological characteristics preserved in a
      single amber deposit. 

PMID- 25970502
TI  - Metabolic profile in early pregnancy is associated with offspring adiposity at 4
      years of age: the Rhea pregnancy cohort Crete, Greece.
AB  - CONTEXT: Maternal pre-pregnancy obesity may increase the risk of childhood
      obesity but it is unknown whether other metabolic factors in early pregnancy such
      as lipid profile and hypertension are associated with offspring cardiometabolic
      traits. OBJECTIVE: Our objective was to investigate whether fasting lipid,
      glucose, and insulin levels during early pregnancy and maternal pre-pregnancy
      weight status, are associated with offspring adiposity measures, lipid levels and
      blood pressure at preschool age. DESIGN AND METHODS: The study included 618
      mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece.
      Pregnant women were recruited at the first prenatal visit (mean: 12 weeks, SD:
      0.7). A subset of 348 women provided fasting serum samples for glucose and lipid
      measurements. Outcomes measures were body mass index, abdominal circumference,
      sum of skinfold thickness, and blood pressure measurements at 4 years of age. A
      subsample of 525 children provided non-fasting blood samples for lipid
      measurements. RESULTS: Pre-pregnancy overweight/obesity was associated with
      greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81),
      central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10 mm
      (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in
      girls. An increase of 40 mg/dl in fasting serum cholesterol levels in early
      pregnancy was associated with greater skinfold thickness by 3.30 mm (95%CI: 1.41,
      5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other
      confounders. An increase of 10 mmHg in diastolic blood pressure in early
      pregnancy was associated with increased risk of offspring overweight/obesity (RR:
      1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71 mm (95% CI:
      0.57, 2.86) at 4 years of age. CONCLUSIONS: Metabolic dysregulation in early
      pregnancy may increase the risk of obesity at preschool age.

PMID- 25970503
TI  - Antibiotics in early life alter the gut microbiome and increase disease incidence
      in a spontaneous mouse model of autoimmune insulin-dependent diabetes.
AB  - Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose
      incidence steadily increased over the past decades in industrialized countries.
      Recent evidence suggests the importance of the gut microbiota to explain this
      trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune
      type 1 diabetes were treated with different antibiotics to explore the influence
      of a targeted intestinal dysbiosis in the progression of the disease. A mixture
      of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or
      vancomycin alone were administered orally from the moment of conception, treating
      breeding pairs, and during the postnatal and adult life until the end of follow
      up at 40 weeks. Diabetes incidence significantly and similarly increased in male
      mice following treatment with these two antibiotic regimens. In NOD females a
      slight yet not significant trend towards an increase in disease incidence was
      observed. Changes in gut microbiota composition were assessed by sequencing the
      V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture
      resulted in near complete ablation of the gut microbiota. Vancomycin treatment
      led to increased Escherichia, Lactobacillus and Sutterella genera and decreased
      members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and
      Rikenellaceae families, as compared to control mice. Massive elimination of IL-17
      producing cells, both CD4+TCRalphabeta+ and TCRgammadelta+ T cells was observed
      in the lamina propria of the ileum and the colon of vancomycin-treated mice.
      These results show that a directed even partial ablation of the gut microbiota,
      as induced by vancomycin, significantly increases type 1 diabetes incidence in
      male NOD mice thus prompting for caution in the use of antibiotics in pregnant
      women and newborns. 

PMID- 25970504
TI  - The relationship between cytotoxin-associated gene A positive Helicobacter pylori
      infection and autoimmune thyroid disease.
AB  - OBJECTIVE: The aim of this study was to determine whether there is an association
      between cagA [cytotoxin-associated gene A] positivity and thyroid autoimmunity
      and thyroid volume. METHODS: This prospective study included 78 Helicobacter
      pylori-positive (H. pylori) dyspeptic patients in the study group, and 50 age-,
      gender-, and body mass index-matched H. pylori-negative dyspeptic patients in the
      control group. All the controls were evaluated via upper gastrointestinal
      endoscopic biopsy or breath test, and were found as H. pylori negative. Gastric
      biopsy specimens were obtained via endoscopy and histological examination was
      performed for documentation of H. pylori. RESULTS: In all, 55.1% (n = 43) of the
      H. pylori-positive patients were cagA positive. There was no significant
      difference in metabolic syndrome parameters or thyroid function test results
      between the study and control groups. The frequency of anti-TPO and Hashimoto's
      thyroiditis positivity was significantly higher in the study group than in the
      control group. Thyroid volume was higher and severe parenchymal heterogeneity was
      more common in the H. pylori-positive patients. CONCLUSIONS: H. pylori infection
      might be a risk factor for autoimmune thyroid disease and high thyroid volume in
      patients diagnosed with histological evaluation. However, cagA positivity has no
      additional effect on these parameters.

PMID- 25970505
TI  - Pharmacogenomic predictors of neonatal abstinence syndrome: correlation with
      length of stay.

PMID- 25970507
TI  - High-Throughput Validated Method for the Quantitation of Busulfan in Plasma Using
      Ultrafast SPE-MS/MS.
AB  - BACKGROUND: Busulfan is an alkylating agent used to ablate bone marrow cells
      before hematopoietic stem cell transplantation. Because of its highly variable
      pharmacokinetics, studies have shown that therapeutic drug monitoring is
      clinically useful for patients undergoing bone marrow transplant so that toxic
      effects associated with high drug exposure could be reduced and improve clinical
      outcomes. Current methods for assaying busulfan include the use of gas
      chromatography mass spectrometry (GC/MS), high-performance liquid chromatography,
      and liquid chromatography mass spectrometry. The clinical need for faster
      turnaround times and increased testing volumes has required laboratories to
      develop faster methods of analysis for higher throughput of samples. Therefore,
      we present a method for the quantification of busulfan in plasma using an
      ultrafast solid-phase extraction/tandem mass spectrometry, which has much faster
      sample cycle times and similar analytical results to GC/MS. METHOD: Calibration
      standards, quality controls, and patient samples after addition of busulfan-d4
      internal standard were extracted into n-butyl chloride from plasma. The organic
      fraction was dried and reconstituted in 600 MUL of water containing ammonium
      acetate, trifluoroacetic acid, and formic acid. Sample analysis was performed at
      a rate of less than 20 seconds per sample using a Rapidfire 300 system coupled to
      an Agilent 6490 MS/MS using electrospray ionization in positive ion mode.
      Concentrations were calculated based on a 5-point calibration curve using a 1/x
      linear curve fit. RESULTS: The analytical method shows excellent precision,
      sensitivity, and specificity. Minimal ion suppression or enhancement due to the
      matrix effect was observed. No significant carryover was seen following a sample
      containing 15,000 ng/mL of busulfan. Seventy-two patient samples were cross
      validated with a current GC/MS method. All patient results throughout the
      analytical range correlated within the acceptance criteria of +/-20%. The linear
      regression demonstrated the following: slope = 1.0067, r = 0.9964, and intercept
      = -6.2. CONCLUSIONS: A simple, fast, and robust method was developed for the
      quantitation of busulfan in plasma with solid-phase extraction/tandem mass
      spectrometry cycle times of <20 seconds per sample.

PMID- 25970506
TI  - Long-term cross-validation of everolimus therapeutic drug monitoring assays: the
      Zortracker study.
AB  - BACKGROUND: This ongoing academic collaboration was initiated for providing
      support to set up, validate, and maintain everolimus therapeutic drug monitoring
      assays and to study long-term interlaboratory performance. METHODS: This study
      was based on EDTA whole blood samples collected from transplant patients treated
      with everolimus in a prospective clinical trial. Samples were handled under
      controlled conditions during collection, storage and were shipped on dry ice to
      minimize freeze-thaw cycles. For more than 1.5 years, participating laboratories
      received a set of 3 blinded samples on a monthly basis. Among others, these
      samples included individual patient samples, patient sample pools to assess long
      term performance, and patient samples pools enriched with isolated everolimus
      metabolites. RESULTS: The results between liquid chromatography coupled with
      tandem mass spectrometry (LC-MS/MS) and the everolimus Quantitative Microsphere
      System (QMS, Thermo Fisher) assay were comparable. The monthly interlaboratory
      variability (coefficient of variation %) for cross-validation samples ranged from
      6.5% to 23.2% (average of 14.8%) for LC-MS/MS and 4.2% to 26.4% (average of
      11.1%) for laboratories using the QMS assay. A blinded long-term pool sample was
      sent to the laboratories for 13 months. The result was 5.31 +/- 0.86 ng/mL
      (range, 2.9-7.8 ng/mL) for the LC-MS/MS and 5.20 +/- 0.54 ng/mL (range, 4.0-6.8
      ng/mL) for QMS laboratories. Enrichment of patient sample pools with 5-25 ng/mL
      of purified everolimus metabolites (46-hydroxy everolimus and 39-O-desmethyl
      everolimus) did not affect the results of either LC-MS/MS or QMS assays.
      CONCLUSIONS: Both LC-MS/MS and QMS assays gave similar results and showed similar
      performance, albeit with a trend toward higher interlaboratory variability among
      laboratories using LC-MS/MS than the QMS assay.

PMID- 25970508
TI  - Isotope-dilution gas chromatography-mass spectrometry method for the analysis of
      hydroxyurea.
AB  - BACKGROUND: Hydroxyurea is used in the treatment of various malignancies and
      sickle cell disease. There are limited studies on the pharmacokinetics of
      hydroxyurea, particularly in pediatric patients. An accurate, precise, and
      sensitive method is needed to support such studies and to monitor therapeutic
      adherence. We describe a novel gas chromatography-mass spectrometry (GC-MS)
      method for the determination of hydroxyurea concentration in plasma using stable
      labeled hydroxyurea C N2 as an internal standard. METHODS: The method involved an
      organic extraction followed by the preparation of trimethylsilyl (TMS)
      derivatives of hydroxyurea for GC-MS selected ion-monitoring analysis. The
      following mass-to-charge (m/z) ratio ions for silated hydroxyurea and hydroxyurea
      C N2 were monitored: hydroxyurea-quantitative ion 277, qualifier ions 292 and
      249; hydroxyurea C N2-quantitative ion 280, qualifier ion 295. This method was
      evaluated for reportable range, accuracy, within-run and between-run
      imprecisions, and limits of quantification. RESULTS: The reportable range for the
      method was 0.1-100 mcg/mL. All results were accurate within an allowable error of
      15%. Within-run and between-run imprecisions were <15%. Samples were stable for
      at least 4 hours at room temperature, 2 months at -20 degrees C, and 6 months at 
      70 degrees C, and after 3 freeze/thaw cycles. Extraction efficiency for 1-, 5-,
      10-, and 50-mcg/mL samples averaged 2.2%, 1.8%, 1.6%, and 1.4%, respectively.
      CONCLUSIONS: The isotope-dilution GC-MS method for analysis of hydroxyurea
      described here is accurate, sensitive, precise, and robust. Its characteristics
      make the method suitable for supporting pharmacokinetic studies and/or clinical
      therapeutic monitoring.

PMID- 25970509
TI  - Describing Assay Precision-Reciprocal of Variance Is Correct, Not CV Percent: Its
      Use Should Significantly Improve Laboratory Performance.
AB  - BACKGROUND: Describing assay error as percent coefficient of variation (CV%)
      fails as measurements approach zero. Results are censored if below some
      arbitrarily chosen lower limit of quantification (LLOQ). CV% gives incorrect
      weighting to data obtained by therapeutic drug monitoring, with incorrect
      parameter values in the resulting pharmacokinetic models, and incorrect dosage
      regimens for patient care. METHODS: CV% was compared with the reciprocal of the
      variance (1/var) of each assay measurement. This method has not been considered
      by the laboratory community. A simple description of assay standard deviation
      (SD) as a polynomial function of the assay measurement over its working range was
      developed, the reciprocal of the assay variance determined, and its results
      compared with CV%. RESULTS: CV% does not provide correct weighting of measured
      serum concentrations as required for optimal therapeutic drug monitoring. It does
      not permit optimally individualized models of the behavior of a drug in a
      patient, resulting in incorrect dosage regimens. The assay error polynomial
      described here, using 1/var, provides correct weighting of such data, all the way
      down to and including zero. There is no need to censor low results, and no need
      to set any arbitrary LLOQ. CONCLUSIONS: Reciprocal of variance is the correct
      measure of assay precision and should replace CV%. The information is easily
      stored as an assay error polynomial. The laboratory can serve the medical
      community better. There is no longer any need for LLOQ, a significant
      improvement. Regulatory agencies should implement this more informed policy.

PMID- 25970510
TI  - Decreased Escitalopram Concentrations Post-Roux-en-Y Gastric Bypass Surgery.
AB  - BACKGROUND: There is a high coincidence between obesity and psychiatric disorders
      including depression. Depressive disorders are commonly treated with
      antidepressants, including the selective serotonin reuptake inhibitor Lexapro
      (escitalopram). Although candidates for elective Roux-en-Y gastric bypass (RYGB)
      surgery may be treated with escitalopram, drug dosing strategies are typically
      not adjusted postoperatively. Therefore, studies are needed to better
      characterize escitalopram drug concentrations in a postsurgical setting. METHODS:
      Turbulent flow-liquid chromatographic-tandem mass spectrometric methods were used
      to quantify escitalopram concentrations in serum in study participants approved
      for RYGB. Blood was collected from study subjects 2 weeks before surgery, and 2
      and 6 weeks postoperatively, to assess the impact of RYGB on systemic drug
      concentrations. RESULTS: Twelve samples from 4 study participants were collected
      and analyzed for serum escitalopram concentrations. Two weeks post-RYGB, although
      there were minimal changes in each participant's body mass index (<5%), drug
      concentrations were 33% (4%-71%) decreased as compared with presurgical serum
      concentrations. There were further decreases in drug concentrations 6 weeks
      postsurgery. All clinical laboratory values were within normal reference
      intervals. CONCLUSIONS: RYGB significantly alters the gastrointestinal tract and
      impacts escitalopram drug concentrations, even shortly after surgery.

PMID- 25970511
TI  - Rapid-Eye-Movement-Sleep (REM) Associated Enhancement of Working Memory
      Performance after a Daytime Nap.
AB  - The main objective was to study the impact of a daytime sleep opportunity on
      working memory and the mechanism behind such impact. This study adopted an
      experimental design in a sleep research laboratory. Eighty healthy college
      students (Age:17-23, 36 males) were randomized to either have a polysomnography
      monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group,
      n=40) between the two assessment sessions. All participants completed a sleep
      diary and wore an actigraph-watch for 5 days before and one day after the
      assessment sessions. They completed the state-measurement of sleepiness and
      affect, in addition to a psychomotor vigilance test and a working memory task
      before and after the nap/wake sessions. The two groups did not differ in their
      sleep characteristics prior to and after the lab visit. The Nap-group had higher
      accuracy on the working memory task, fewer lapses on the psychomotor vigilance
      test and lower state-sleepiness than the Wake-group. Within the Nap-group,
      working memory accuracy was positively correlated with duration of rapid eye
      movement sleep (REM) and total sleep time during the nap. Our findings suggested
      that "sleep gain" during a daytime sleep opportunity had significant positive
      impact on working memory performance, without affecting subsequent nighttime
      sleep in young adult, and such impact was associated with the duration of REM.
      While REM abnormality has long been noted in pathological conditions (e.g.
      depression), which are also presented with cognitive dysfunctions (e.g. working
      memory deficits), this was the first evidence showing working memory enhancement
      associated with REM in daytime napping in college students, who likely had
      habitual short sleep duration but were otherwise generally healthy. 

PMID- 25970512
TI  - Sialendoscopy-Assisted Treatment for Chronic Obstructive Parotitis-Our Treatment
      Strategy with 31 Patients.
AB  - PURPOSE: Chronic obstructive parotitis (COP) is the most common non-neoplastic
      salivary disorder. The aim of this study was to describe the authors' experience
      using sialendoscopy for diagnosing and treating COP. MATERIALS AND METHODS:
      Thirty-one patients with COP who were treated with sialendoscopy from January
      2013 through June 2014 at the Department of Oral and Maxillofacial Surgery,
      School of Stomatology, China Medical University (Shenyang, China) were
      retrospectively reviewed. The cohort underwent ultrasonography and salivary gland
      scintigraphy examinations before sialendoscopy. Patients without stones underwent
      sialography before surgery. All patients were asked to report visual analog scale
      (VAS) scores before and 6 months after surgery to evaluate their condition. A
      paired t test was conducted and differences with a P value less than .05 were
      considered statistically significant. RESULTS: Thirty patients (44 parotid
      glands) successfully underwent interventional sialendoscopy under local
      anesthesia; 1 patient (1 parotid gland) received general anesthesia. The mean
      preoperative VAS score was 6, and the mean VAS score 6 months after sialendoscopy
      was 4.9. The postoperative VAS score was significantly lower than the
      preoperative VAS score (P < .05). CONCLUSIONS: Interventional sialendoscopy plays
      an important role in the treatment of COP.

PMID- 25970513
TI  - Treatment of Intermittent Locking of the Jaw in Wilkes Stage II Derangement by
      Arthroscopic Lysis and Lavage.
AB  - PURPOSE: This study evaluated the efficacy of a standardized arthroscopic lysis
      and lavage in decreasing the intermittent locking and transient pain episodes
      that characterize patients with early- to intermediate-stage internal derangement
      (Wilkes stage II). PATIENTS AND METHODS: This is a retrospective analysis of the
      medical records of 27 patients (39 joints) treated by arthroscopic lysis and
      lavage in the authors' department during a 2.5-year period. Patients were
      diagnosed preoperatively as having mild internal derangement (Wilkes stage II)
      that was unresponsive to previous conservative therapy. Three outcome variables
      were used to assess the efficacy of treatment: 1) frequency of intermittent
      locking or catching episodes, 2) severity of pain, and 3) maximal interincisal
      opening. RESULTS: Ninety-two percent of patients reported improvement regarding
      the locking and catching episodes. Most patients (77%) denied experiencing any
      locking episodes during the follow-up period, and 15% reported experiencing
      locking episodes but with less frequency or severity. The median duration of
      symptoms for patients who were freed from locking episodes was 16 months compared
      with 36 months for patients who still had locking episodes after treatment (P =
      .059). Mean pain values (visual analog scale, 0 to 10) decreased from 7.5
      preoperatively to 3.2 postoperatively (P < .0001). For maximal interincisal
      opening, there was no significant difference after treatment (mean, 39.4 mm
      preoperatively vs 41.3 mm postoperatively; P = .06). Success was defined as a
      decrease in locking episodes, a decrease of pain, and maintenance of normal
      interincisal opening (>36 mm). The overall success rate was 81.4% (22 of 27
      patients). CONCLUSION: Arthroscopic lysis and lavage is an efficient treatment
      modality for treating mild internal derangement of the temporomandibular joint.
      It decreases the frequency of locking episodes and decreases transient pain
      periods.

PMID- 25970514
TI  - Do Mandibular Advancement Devices Influence Patients' Snoring and Obstructive
      Sleep Apnea? A Cone-Beam Computed Tomography Analysis of the Upper Airway Volume.
AB  - PURPOSE: The upper airway volume is central to the development and treatment of
      snoring and obstructive sleep apnea, and mandibular advancement devices (MADs)
      have increasingly been used as an effective alternative to continuous positive
      airway pressure for these 2 conditions. We investigated the changes in breathing
      patterns and upper airway volume parameters measured on cone-beam computed
      tomography (CBCT) scans of patients with and without the use of custom-made MADs.
      MATERIALS AND METHODS: We performed a prospective study at the Department of Oral
      and Maxillofacial Surgery, Odense University Hospital, on consecutively treated
      patients. CBCT scans were performed with and without the MAD to measure the
      changes in the upper airway volume. The patients underwent diagnostic
      cardiorespiratory monitoring before and after 3 months of MAD therapy.
      Measurements with and without MAD were compared using Student's t test and the
      Wilcoxon signed rank test, and mixed-model analyses were performed adjusting for
      sleep apnea severity, type 2 diabetes, body mass index, gender, and age. RESULTS:
      A total of 44 patients (31 men and 13 women, age 50 +/- 13 years, body mass index
      31 +/- 5.6 kg/m(2)) completed the trial. MAD therapy was associated with an
      increase in the total upper airway volume from 22.9 +/- 8.7 cm(3) before
      treatment to 26.7 +/- 10.7 cm(3) after treatment (P < .001). MAD therapy reduced
      the apnea-hypopnea index (AHI) from 15.8 +/- 17.4 events/hour before treatment to
      6.2 +/- 9.8 events/hour after treatment (P < .001). CONCLUSION: The results of
      the present study indicate that MAD therapy appears to produce significant
      changes in the upper airway volume that correlate with a decrease in the AHI.

PMID- 25970515
TI  - Repair of Oroantral Communications by Use of a Combined Surgical Approach:
      Functional Endoscopic Surgery and Buccal Advancement Flap/Buccal Fat Pad Graft.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of a combined
      surgical approach for repair of oroantral communications. MATERIALS AND METHODS:
      This retrospective study evaluated the effectiveness of the combined surgical
      approach of functional endoscopic sinus surgery and buccal advancement flap or
      buccal fat pad grafting. Forty-three patients with chronic sinusitis from 2007 to
      2013 were evaluated after combined functional endoscopic sinus surgery and
      closure of oroantral communication with a buccal fat pad graft or buccal
      advancement flap for persistent oroantral communication. Treatment included
      preoperative computed tomography, antibiotic therapy, exploration and removal of
      sinus pathologic tissues, rotation of a pedicled fat pad graft into the oral
      opening, repair and closure of oral mucosa, exploration of involved sinuses with
      excision of sinus and nasal tissues necessary for establishment of osteomeatal
      drainage, and follow-up to evaluate the success or failure of treatment. RESULTS:
      The results were overwhelmingly positive, with 17 of 19 buccal advancement flaps
      showing no dehiscence or chronic sinusitis and all 24 buccal fat pad grafts
      showing no dehiscence, with no continued sinus complaints. Complications ranged
      from a sensation of tightness in the graft area to paresthesia of nerve V2. There
      was no statistical difference in results between buccal fat pad grafts and buccal
      advancement flaps. CONCLUSION: The results of this study infer that a combined
      approach to the multifactorial disease process results in a very successful and
      predictable outcome.

PMID- 25970516
TI  - Complete mitochondrial genome of Hepialus gonggaensis (Lepidoptera: Hepialidae),
      the host insect of Ophiocordyceps sinensis.
AB  - The complete mitochondrial genome sequence of Hepialus gonggaensis was sequenced
      for the first time. The complete mtDNA sequence was 15,940 bp in length and
      contained 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and an AT-rich
      region, the gene composition and the arrangement of which were identical to other
      insects of Hepialidae. The overall base composition of the heavy strand was
      41.14% A, 40.24% T, 11.17% C, and 7.45% G, with an AT content of 81.37%. The
      necleotide sequence data of 13 protein-coding genes of H. gonggaensis and other
      10 Lepidoptera species were used for constructing the phylogenetic tree. It
      revealed that H. gonggaensis and other four Hepialidae species were clustered to
      a clade with high bootstraps values.

PMID- 25970517
TI  - Potential of the Desert Locust Schistocerca gregaria (Orthoptera: Acrididae) as
      an Unconventional Source of Dietary and Therapeutic Sterols.
AB  - Insects are increasingly being recognized not only as a source of food to feed
      the ever growing world population but also as potential sources of new products
      and therapeutic agents, among which are sterols. In this study, we sought to
      profile sterols and their derivatives present in the desert locust, Schistocerca
      gregaria, focusing on those with potential importance as dietary and therapeutic
      components for humans. Using coupled gas chromatography-mass spectrometry (GC
      MS), we analyzed and compared the quantities of sterols in the different sections
      of the gut and tissues of the locust. In the gut, we identified 34 sterols which
      showed a patchy distribution, but with the highest composition in the foregut
      (55%) followed by midgut (31%) and hindgut (14%). Fed ad libitum on wheat
      seedlings, five sterols unique to the insect were detected. These sterols were
      identified as 7-dehydrocholesterol, desmosterol, fucosterol, (3beta, 5alpha)
      cholesta-8, 14, 24-trien-3-ol, 4, 4-dimethyl, and (3beta, 20R) cholesta-5, 24
      dien-3, 20-diol with the first three having known health benefits in humans.
      Incubation of the fore-, mid- and hindgut with cholesterol-[4-13C] yielded eight
      derivatives, three of these were detected in the gut of the desert locust after
      it had consumed the vegetative diet but were not detected in the diet. Our study
      shows that the desert locust ingests phytosterols from a vegetative diet and,
      amplifies and metabolizes them into derivatives with potential salutary benefits
      and we discuss our findings in this context. 

PMID- 25970518
TI  - Assessment of the accuracy and precision of the i-Smart 30 VET Electrolyte
      Analyzer in dogs, cats, cattle and pigs.
AB  - BACKGROUND: Performance evaluation of point-of-care (POC) electrolyte analyzers
      is essential for determining their precision and accuracy in clinical practice.
      OBJECTIVE: The purpose of this study was to validate the i-Smart 30 VET
      Electrolyte Analyzer for canine, feline, bovine, and porcine samples in
      comparison with the ion-selective electrolyte analyzer Roche 9180 electrolyte
      analyzer. METHODS: A total of 400 heparinized whole blood samples were collected
      and analyzed by both instruments for sodium, potassium, and chloride
      concentrations. Within-run, between-day, and total imprecision were evaluated.
      Statistical analyses included tests for correlation, regression, bias, and total
      error. RESULTS: The coefficients of variation (CV) of both within-run and between
      day imprecisions in the i-Smart 30 VET ranged from 0.4-1.6%. In addition, total
      CV (0.3-1.7%) and total error (0.7-3.7%) of the i-Smart 30 VET were acceptable
      according to the ASVCP guidelines (< 5%). The correlation between the i-Smart 30
      VET and the Roche 9180 was excellent (r > .98). There was no proportional error
      according to the regression (slope ranges 0.92-1.00, 95% CI includes 1.00), but a
      constant error was detected for sodium concentration in dogs (interval = 0.5),
      cattle (interval = 3.0), and pigs (interval = 4.0), and for chloride
      concentration in cats (interval = 1.0). Most of the bias was within 95% CI, and
      the total error range (0.8-3.5%) was acceptable according to ASVCP guidelines.
      CONCLUSION: The i-Smart 30 VET Electrolyte Analyzer provides precise and accurate
      measurements of sodium, potassium, and chloride concentrations in whole blood
      samples from dogs, cats, cattle, and pigs.

PMID- 25970519
TI  - Digital gangrene and hepatitis C: a diagnostic and therapeutic dilemma.

PMID- 25970520
TI  - Determination of size- and number-based concentration of silica nanoparticles in
      a complex biological matrix by online techniques.
AB  - We propose for the first time methodology for the determination of a number-based
      concentration of silica (SiO2) nanoparticles (NP) in biological serum using
      nanoparticle tracking analysis (NTA) as the online detector for asymmetric flow
      field-flow fractionation (AF4). The degree of selectivity offered by AF4 was
      found necessary to determine reliably number-based concentration of the measured
      NP in the complex matrix with a relative measurement error of 5.1% (as relative
      standard deviation, n = 3) and without chemical sample pretreatment. The
      simultaneous online coupling to other size and concentration detectors, such as
      multiangle light scattering (MALS) and ICPMS, for the measurement of the same NP
      suspension, was used to confirm the particle size determined with NTA and the
      equivalent particle number determined by AF4/NTA, respectively. The size- and
      number-based concentration data obtained by independent techniques were in a good
      agreement. The developed methodology can easily be extended to other types of
      particles or particle suspensions and other complex matrices provided that the
      particle size is above the limit of detection for NTA. 

PMID- 25970521
TI  - Constrained Unfolding of a Helical Peptide: Implicit versus Explicit Solvents.
AB  - Steered Molecular Dynamics (SMD) has been seen to provide the potential of mean
      force (PMF) along a peptide unfolding pathway effectively but at significant
      computational cost, particularly in all-atom solvents. Adaptive steered molecular
      dynamics (ASMD) has been seen to provide a significant computational advantage by
      limiting the spread of the trajectories in a staged approach. The contraction of
      the trajectories at the end of each stage can be performed by taking a structure
      whose nonequilibrium work is closest to the Jarzynski average (in naive ASMD) or
      by relaxing the trajectories under a no-work condition (in full-relaxation ASMD-
      namely, FR-ASMD). Both approaches have been used to determine the energetics and
      hydrogen-bonding structure along the pathway for unfolding of a benchmark peptide
      initially constrained as an alpha-helix in a water environment. The energetics
      are quite different to those in vacuum, but are found to be similar between
      implicit and explicit solvents. Surprisingly, the hydrogen-bonding pathways are
      also similar in the implicit and explicit solvents despite the fact that the
      solvent contact plays an important role in opening the helix.

PMID- 25970523
TI  - Aberrant function of learning and cognitive control networks underlie inefficient
      cognitive flexibility in anorexia nervosa: a cross-sectional fMRI study.
AB  - OBJECTIVES: People with Anorexia Nervosa exhibit difficulties flexibly adjusting
      behaviour in response to environmental changes. This has previously been
      attributed to problematic behavioural shifting, characterised by a decrease in
      fronto-striatal activity. Additionally, alterations of instrumental learning,
      which relies on fronto-striatal networks, may contribute to the observation of
      inflexible behaviour. The authors sought to investigate the neural correlates of
      cognitive flexibility and learning in Anorexia Nervosa. METHOD: Thirty-two adult
      females with Anorexia Nervosa and thirty-two age-matched female control
      participants completed the Wisconsin Card Sorting Task whilst undergoing
      functional magnetic resonance imaging. Event-related analysis permitted the
      comparison of cognitive shift trials against those requiring maintenance of rule
      sets and allowed assessment of trials representing learning. RESULTS: Although
      both groups performed similarly, we found significant interactions in the left
      middle frontal gyrus, precuneus and superior parietal lobule whereby blood
      oxygenated-level dependent response was higher in Anorexia Nervosa patients
      during shifting but lower when maintaining rule-sets, as compared to healthy
      controls. During learning, posterior cingulate cortex activity in healthy
      controls decreased whilst increasing in the Anorexia Nervosa group, whereas the
      right precuneus exhibited the opposite pattern. Furthermore, learning was
      associated with lower blood-oxygenated-level dependent response in the caudate
      body, as compared to healthy controls. CONCLUSIONS: People with Anorexia Nervosa
      display widespread changes in executive function. Whilst cognitive flexibility
      appears to be associated with aberrant functioning of the fronto-parietal control
      network that mediates between internally and externally directed cognition,
      fronto-striatal alterations, particularly within the caudate body, were
      associated with instrumental learning. Together, this shows how perseverative
      tendencies could be a substrate of multiple high-order processes that may
      contribute to the maintenance of Anorexia Nervosa.

PMID- 25970524
TI  - Clinical benefits of routine varicella vaccination for adults.
AB  - Varicella is a highly contagious disease caused by varicella zoster virus. In
      children, it is generally a mild to moderate illness while it is often more
      severe in adults, with serious complications as dehydration, pneumonia, bleeding
      problems, infection or inflammation of the brain, secondary bacterial infections,
      sepsis, toxic shock syndrome, bone infections, joint infections and deaths. Some
      groups of adults are at major risk of complications, in particular
      immunocompromised persons as subjects with impaired humoral immunity and who is
      receiving systemic steroids, persons who live or work in environments in which
      transmission of varicella is likely, health-care personnel and pregnant women.
      After the introduction of Universal Mass Vaccination (UMV), the first
      mathematical models suggested that vaccination will lead to a shift in the
      average age at infection from children to adults with an increasing numbers of
      complicated forms, nevertheless new models predicted that, although an upward
      shift in the age at infection may occur, the overall morbidity due to varicella
      is likely to decrease. Current literature seems to suggest that for public health
      authorities the key action to prevent an increase of varicella incidence among
      adults is to achieve high vaccination coverage among babies and adolescents in
      countries who adopted UMV. 

PMID- 25970525
TI  - PKC in rat dorsal raphe nucleus plays a key role in sleep-wake regulation.
AB  - Studies suggest a tight relationship between protein kinase C (PKC) and circadian
      clock. However, the role of PKC in sleep-wake regulation remains unclear. The
      present study was conducted to investigate the role of PKC signaling in sleep
      wake regulation in the rat. Our results showed that the phosphorylation level of
      PKC in dorsal raphe nucleus (DRN) was decreased after 6h sleep deprivation, while
      no alterations were found in ventrolateral preoptic nucleus (VLPO) or locus
      coeruleus (LC). Microinjection of a pan-PKC inhibitor, chelerythrine chloride
      (CHEL, 5 or 10nmol), into DRN of freely moving rats promoted non rapid eye
      movement sleep (NREMS) without influences on rapid eye movement sleep (REMS).
      Especially, CHEL application at 5nmol increased light sleep (LS) time while CHEL
      application at 10nmol increased slow wave sleep (SWS) time and percentage. On the
      other hand, microinjection of CaCl2 into DRN not only increased the
      phosphorylation level of PKC, but also reduced NREMS time, especially SWS time
      and percentage. While CHEL abolished the inhibitory effect of CaCl2 on NREMS and
      SWS. These data provide the first direct evidence that inhibition of
      intracellular PKC signaling in DRN could increase NREMS time including SWS time
      and percentage, while activation of PKC could suppress NREMS and reduce SWS time
      and percentage. These novel findings further our understanding of the basic
      cellular and molecular mechanisms of sleep-wake regulation. 

PMID- 25970526
TI  - Dealing with resistance in temporary agency nurses. The role of fear in identity
      building processes.
AB  - PURPOSE: The purpose of this paper is to interpret employees' resistance using
      the perspective of a Foucaultian/post-structuralist approach in critical
      management studies. The authors examine the relationship between management of
      diversity, based on employment contract, emotional construction of identity and
      processes of resistance. The authors explore the ways in which temporary agency
      nurses understand and experience their contract, respond to tensions regarding
      temporary employment, develop collective emotions and show processes of
      resistance. DESIGN/METHODOLOGY/APPROACH: The study adopted an interpretive and
      qualitative approach. The authors analysed empirical material collected in the
      Haematology Department of a hospital in Naples, Italy, to illustrate actual
      experiences in the workplace. FINDINGS: Fear turns out to be the discursive
      resource through which resistance is actually exerted. Through emotions,
      temporary nurses build a community of coping and enhance their collective
      identity. They use fear to develop solidarity and to mobilize collective
      resistance in the workplace. Although no traditional resistance behaviours are
      reported, they aim to undermine the reputation of top managers and challenge and
      re-write the prevailing discourses of the organization. ORIGINALITY/VALUE: The
      paper contributes to the critical literature because the authors analysed a
      relationship that is rarely theoretically and empirically examined in literature,
      that between employment contract, collective identity-building dynamics and
      processes of resistance. We showed that the creation of a community of coping
      enabled minorities to voice their distance from and opposition to management.

PMID- 25970527
TI  - How professional identity shapes youth healthcare.
AB  - PURPOSE: The primary care sector is experiencing considerable change. How change
      and uncertainty are accommodated by the professional identity of medicine has not
      been examined. The purpose of this paper is to address the youth healthcare as an
      exemplar as this field is often a source of uncertainty for general practitioners
      (GPs). DESIGN/METHODOLOGY/APPROACH: Using heterogeneity sampling, 22 GPs
      participated in focus groups to explore perceptions of youth healthcare, factors
      that help and hinder it, and training needs. Analysis of the research material
      was guided by a theoretical model on professional identity. FINDINGS: GPs
      described tensions that challenged their professional identity - the challenges
      of working with young people and their complex issues, the extent to which youth
      healthcare sits within the purview of general practice, and the scope of training
      required. These tensions appeared to destabilise professional identity. Some
      participants had customised their identity by enriching understandings of and
      approach to general practice. Participants also reported work customisation as a
      way of managing the complex demands of the general practice role. Deepened
      insight appeared to bolster perceived capacity to support a complex patient
      cohort. Research limitations/implications - Participants are not representative
      of the primary care sector - furthermore, the methodology limits the
      generalisability of the findings. PRACTICAL IMPLICATIONS: To bolster youth
      health, mere clinician training is insufficient. Youth health requires explicit
      support from governments and training providers to be incorporated into the
      healthcare landscape. ORIGINALITY/VALUE: This study extends current research on
      professional identity by examining youth healthcare within the changing context
      of primary care.

PMID- 25970528
TI  - Preoperative cross functional teams improve OR performance.
AB  - PURPOSE: The purpose of this paper is to present the effect of the introduction
      of cross-functional team (CFT)-based organization, rather than, on planning and
      performance of OR teams. DESIGN/METHODOLOGY/APPROACH: In total, two surgical
      departments of the Radboud University Nijmegen Medical Center (RUNMC) in the
      Netherlands were selected to illustrate the effect on performance. Data were
      available for a total of seven consecutive years from 2005 until 2012 and
      consisted of 4,046 OR days for surgical Department A and 1,154 OR days for
      surgical Department B on which, respectively 8,419 and 5,295 surgical cases were
      performed. The performance indicator "raw utilization" of the two surgical
      Departments was presented as box-and-whisker plots per year (2005-2011). The
      relationship between raw utilization (y) and years (x) was analyzed with linear
      regression analysis, to observe if performance changed over time. FINDINGS: Based
      on the linear regression analysis, raw utilization of surgical Department A
      showed a statistically significant increase since 2006. The variation in raw
      utilization reduced from IQR 33 percent in 2005 to IQR 8 percent in 2011.
      Surgical Department B showed that raw utilization increased since 2005. The
      variation in raw utilization reduced from IQR 21 percent in 2005 to IQR 8 percent
      in 2011. SOCIAL IMPLICATIONS: Hospitals need to improve their productivity and
      efficiency in response to higher societal demands and rapidly escalating costs.
      The RUNMC increased their OR performance significantly by introduction of CFT
      based organization in the operative process and abandoning the so called
      functional silos. ORIGINALITY/VALUE: The stepwise reduction of variation - a
      decrease of IQR during the years - indicates an organizational learning effect.
      This study demonstrates that introducing CFTs improve OR performance by working
      together as a team.

PMID- 25970529
TI  - Professional identity and role transitions in clinical managers.
AB  - PURPOSE: The purpose of this paper is to investigate how clinicians' professional
      background influences their transition into the managerial role and identity as
      clinical managers. DESIGN/METHODOLOGY/APPROACH: The authors interviewed and
      observed 30 clinicians in managerial positions in Norwegian hospitals. FINDINGS:
      A central finding was that doctors experienced difficulties in reconciling the
      role as health professional with the role as manager. They maintained a health
      professional identity and reported to find meaning and satisfaction from clinical
      work. Doctors also emphasized clinical work as a way of gaining legitimacy and
      respect from medical colleagues. Nurses recounted a faster and more positive
      transition into the manager role, and were more fully engaged in the managerial
      aspects of the role. PRACTICAL IMPLICATIONS: The authors advance that health care
      organizations need to focus on role, identity and need satisfaction when
      recruiting and developing clinicians to become clinical managers.
      ORIGINALITY/VALUE: The study suggests that the inclusion of aspects from identity
      and need satisfaction literature expands on and enriches the study of clinical
      managers.

PMID- 25970530
TI  - A qualitative investigation of Foundation Year 2 doctors' views on the European
      Working Time Directive.
AB  - PURPOSE - The purpose of this paper is to examine the personal views and
      experiences of Foundation Year 2 doctors operating under the European Working
      Time Directive (EWTD). DESIGN/METHODOLOGY/APPROACH - In total, 36 Foundation Year
      2 doctors from a single UK-based Deanery participated in this semistructured
      interview study. FINDINGS - Findings indicated that Foundation doctors typically
      welcomed a regulation of working hours, but reported frustration at the manner in
      which the Directive had been implemented. Participants reported concerns at
      reducing hours by removing out-of-hours working in order to meet EWTD
      requirements. Out-of-hours shifts were highly valued owing to their increased
      opportunities for autonomous clinical decision making. By contrast, day-shifts
      were regarded as heavily administrative in nature and were perceived as service
      provision. Foundation doctors discussed the unique nature of the out-of-hours
      working period which appeared to provide specific learning opportunities as
      doctors draw on time management and prioritisation skills. ORIGINALITY/VALUE -
      Given the challenges the EWTD presents, careful rota planning is essential.
      First, the authors would encourage the restructuring of day-shift work to provide
      a greater emphasis on hands-on skills experience in a supportive, supervised
      environment. Second, where possible, Foundation doctors might benefit from the
      opportunity to engage in some out-of-hours working, such as with multi
      professional "Hospital at Night" teams. Third, the authors would encourage junior
      doctor involvement in rota design and planning which may increase their perceived
      autonomy and therefore buy-in of working practices.

PMID- 25970531
TI  - Hospital leadership perspectives on the contributions of Ronald McDonald Houses.
      Results from an international survey.
AB  - PURPOSE: The purpose of this paper is to describe an international survey of
      hospital executives and administrators' perspectives on the contributions of
      their affiliation with a Ronald McDonald House (RMH) as an example of
      accommodation in family-centered care to the hospital's mission, operations and
      patient experience. DESIGN/METHODOLOGY/APPROACH: RMHs worldwide provided the
      names and e-mail addresses of the people holding key leadership positions in
      their main hospital partner, who in turn were invited to complete an internet
      based survey (530 participants; response rate of 54.5 percent). FINDINGS:
      Hospital leaders reported very positive opinions about the contributions of their
      RMHs affiliation to their ability to serve seriously ill children and their
      families. This included such important outcomes as increasing family integrity
      and family participation in care decisions; and decreasing psychosocial stress
      and hospital social work resource burdens associated with lodging, food,
      transportation and sibling support. Hospital chief executive offices (CEOs) and
      medical directors reported very strong and positive opinions regarding the value
      added of their RMHs affiliation in many areas, including enhanced marketing of
      hospital specialty services and reduced length of stay. RESEARCH
      LIMITATIONS/IMPLICATIONS: Survey response bias is a limitation, although the
      results are still useful in terms of identifying multiple ways in which RMHs are
      perceived as contributing to hospitals' operations and provision of family
      centered care. PRACTICAL IMPLICATIONS: Overall, the results suggest that,
      internationally, hospital leaders believe that RMHs play a key and valued role in
      their provision of family-centered care to seriously ill children and their
      families. SOCIAL IMPLICATIONS: Family accommodation is more than the simple
      provision of lodging and plays an integral role how hospitals approach family
      centered care. ORIGINALITY/VALUE: This international study contributes to the
      general literature on the role of family accommodation in hospitals' provision of
      family-centered care and the specific and very sparse literature on RMHs in
      particular.

PMID- 25970532
TI  - Psychological contract breach among allied health professionals.
AB  - PURPOSE: Allied health professionals are vital for effective healthcare yet there
      are continuing shortages of these employees. Building on work with other
      healthcare professionals, the purpose of this paper is to investigate the
      influence of psychological contract (PC) breach and types of organisational
      justice on variables important to retention among allied health professionals:
      mental health and organisational commitment. The potential effects of justice on
      the negative outcomes of breach were examined. DESIGN/METHODOLOGY/APPROACH:
      Multiple regressions analysed data from 113 allied health professionals working
      in a medium-large Australian healthcare organisation. FINDINGS: The main negative
      impacts on respondents' mental health and commitment were from high PC breach,
      low procedural and distributive justice and less respectful treatment from
      organisational representatives. The interaction between procedural justice and
      breach illustrates that breach may be forgivable if processes are fair.
      Surprisingly, a betrayal or "aggravated breach effect" may occur after a breach
      when interpersonal justice is high. Further, negative affectivity was negatively
      related to respondents' mental health (affective outcomes) but not commitment
      (work-related attitude). PRACTICAL IMPLICATIONS: Healthcare organisations should
      ensure the fairness of decisions and avoid breaking promises within their
      control. If promises cannot reasonably be kept, transparency of processes behind
      the breach may allow allied health professionals to understand that the
      organisation did not purposefully fail to fulfil expectations. ORIGINALITY/VALUE:
      This study offers insights into how breach and four types of justice interact to
      influence employee mental health and work attitudes among allied health
      professionals.

PMID- 25970533
TI  - Patient-centred professionalism in pharmacy: values and behaviours.
AB  - PURPOSE: Research on patient-centred professionalism in pharmacy is scarce
      compared with other health professions and in particular with pharmacists early
      in their careers. The purpose of this paper is to explore patient-centred
      professionalism in early career pharmacists and to describe reported behaviours.
      DESIGN/METHODOLOGY/APPROACH - This study explored patient-centred professional
      values and reported behaviours, taking a qualitative approach. In all, 53 early
      career pharmacists, pharmacy tutors and pharmacy support staff, practising in
      community and hospital pharmacy in England took part; the concept of patient
      centred professionalism was explored through focus group interviews and the
      critical incident technique was used to elicit real-life examples of
      professionalism in practice. FINDINGS: Triangulation of the data revealed three
      constructs of pharmacy patient-centred professionalism: being professionally
      competent, having ethical values and being a good communicator. RESEARCH
      LIMITATIONS/IMPLICATIONS: It is not known whether our participants' perspectives
      reflect those of all pharmacists in the early stages of their careers. The data
      provide meaning for the concept of patient-centred professionalism. The work
      could be extended by developing a framework for wider application. Patient
      centred professionalism in pharmacy needs further investigation from the patient
      perspective. PRACTICAL IMPLICATIONS: The findings have implications for pharmacy
      practice and education, particularly around increased interaction with patients.
      SOCIAL IMPLICATIONS: The data contribute to a topic of importance to patients and
      in relation to UK health policy, which allocates more directly clinical roles to
      pharmacists, which go beyond the dispensing and supply of medicines.
      ORIGINALITY/VALUE: The methods included a novel application of the critical
      incident technique, which generated empirical evidence on a previously under
      researched topic.

PMID- 25970534
TI  - Membrane capacitive memory alters spiking in neurons described by the fractional
      order Hodgkin-Huxley model.
AB  - Excitable cells and cell membranes are often modeled by the simple yet elegant
      parallel resistor-capacitor circuit. However, studies have shown that the passive
      properties of membranes may be more appropriately modeled with a non-ideal
      capacitor, in which the current-voltage relationship is given by a fractional
      order derivative. Fractional-order membrane potential dynamics introduce
      capacitive memory effects, i.e., dynamics are influenced by a weighted sum of the
      membrane potential prior history. However, it is not clear to what extent
      fractional-order dynamics may alter the properties of active excitable cells. In
      this study, we investigate the spiking properties of the neuronal membrane patch,
      nerve axon, and neural networks described by the fractional-order Hodgkin-Huxley
      neuron model. We find that in the membrane patch model, as fractional-order
      decreases, i.e., a greater influence of membrane potential memory, peak sodium
      and potassium currents are altered, and spike frequency and amplitude are
      generally reduced. In the nerve axon, the velocity of spike propagation increases
      as fractional-order decreases, while in a neural network, electrical activity is
      more likely to cease for smaller fractional-order. Importantly, we demonstrate
      that the modulation of the peak ionic currents that occurs for reduced fractional
      order alone fails to reproduce many of the key alterations in spiking properties,
      suggesting that membrane capacitive memory and fractional-order membrane
      potential dynamics are important and necessary to reproduce neuronal electrical
      activity. 

PMID- 25970535
TI  - The Effect of Different Phosphorus Chemical States on an Onion-like Carbon
      Surface for the Oxygen Reduction Reaction.
AB  - Two kinds of phosphorus-modified onion-like carbons dominated by C-O-P bonds and
      C-P bonds were fabricated and further used as catalysts in the oxygen reduction
      reaction (ORR). The results show that the bonding state of phosphorus has a
      significant effect on the ORR catalytic activity. The formation of C-O-P bonds
      improves ORR activity, whereas C-P bonds play an adverse role in stabilizing the
      key intermediates during the ORR owing to the distorted graphitic structure, as
      confirmed by the work function value.

PMID- 25970537
TI  - The regular notation for gerontological social workers to have broad skill sets.

PMID- 25970538
TI  - Introduction to the aging military veterans special section.

PMID- 25970536
TI  - Development and validation of a biomarker for diarrhea-predominant irritable
      bowel syndrome in human subjects.
AB  - Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical
      criteria after excluding "organic" conditions, and can be precipitated by acute
      gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria
      that cause acute gastroenteritis, and a post-infectious animal model demonstrates
      that host antibodies to CdtB cross-react with vinculin in the host gut, producing
      an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti
      vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D
      IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter
      clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease
      (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43)
      were obtained for comparison. Subjects with IBD and celiac disease were recruited
      based on the presence of intestinal complaints and histologic confirmation of
      chronic inflammatory changes in the colon or small intestine. Subjects with
      celiac disease were also required to have an elevated tTG and biopsy. All
      subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti
      vinculin antibodies were determined by ELISA, and compared between groups. Anti
      CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy
      controls and celiac disease (P<0.001). Anti-vinculin titers were also
      significantly higher in IBS (P<0.001) compared to the other groups. The area
      under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D
      IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were
      less specific in differentiating IBS from celiac disease. Optimization
      demonstrated that for anti-CdtB (optical density>=2.80) the specificity,
      sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for
      anti-vinculin (OD>=1.68) were 83.8%, 32.6 and 2.0, respectively. These results
      confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS
      compared to non-IBS subjects. These biomarkers may be especially helpful in
      distinguishing D-IBS from IBD in the workup of chronic diarrhea. 

PMID- 25970541
TI  - Measurement of small fibre pain threshold values for the early detection of
      diabetic polyneuropathy.
AB  - AIM: To investigate whether Adelta and C fibre pain threshold values, measured
      using intra-epidermal electrical stimulation (IES), in people with and without
      Type 2 diabetes are useful in evaluating diabetic polyneuropathy (DPN) severity.
      METHODS: Adelta and C fibre pain threshold values were measured in Japanese
      people with (n = 120) and without (n = 76) Type 2 diabetes by IES. Nerve
      conduction studies and other tests were performed to evaluate diabetic
      complications. RESULTS: Adelta and C fibre pain threshold values were high in
      people with diabetes compared with control subjects (Adelta fibre: 0.050 vs.
      0.030 mA, P < 0.01; C fibre: 0.180 vs. 0.070 mA, P < 0.01). Participants with
      diabetes and neuropathy had significantly higher Adelta and C fibre pain
      threshold values than participants without neuropathy (Adelta fibres 0.063 vs.
      0.039 mA, P < 0.01; C fibres 0.202 vs. 0.098 mA, P < 0.05). C fibre pain
      threshold values were significantly higher in participants with diabetes and
      diabetic microvascular complications than in participants without complications.
      Threshold values increased with complication progression. When DPN was diagnosed
      according to the Diabetic Neuropathy Study Group in Japan criteria, the cut-off
      for the C fibre pain threshold values was 0.125 mA (area under the curve 0.758,
      sensitivity 81.5%, specificity 61.5%). The IES test took less time (P < 0.01) and
      was less invasive (P < 0.01) than the nerve conduction studies. CONCLUSIONS:
      Intra-epidermal electrical stimulation is a non-invasive and easy measurement of
      small fibre pain threshold values. It may be clinically useful for C fibre
      measurement to diagnose early DPN as defined by the Diabetic Neuropathy Study
      Group in Japan criteria.

PMID- 25970542
TI  - An appendectomy increases the risk of rheumatoid arthritis: a five-year follow-up
      study.
AB  - Many studies have reported a possible association of an appendectomy with
      rheumatoid arthritis (RA). However, findings of the relationship between an
      appendectomy and RA remain inconsistent. Furthermore, all such studies were
      conducted in Western societies, and relevant studies on the relationship between
      an appendectomy and RA in Asian countries are still lacking. In this study, we
      investigated the relationship between an appendectomy and the subsequent risk of
      RA using a population-based dataset. We retrieved data for this retrospective
      cohort study from the Taiwan "Longitudinal Health Insurance Database 2005". We
      included 4,294 subjects who underwent an appendectomy in the study cohort and
      12,882 matched subjects in the comparison cohort. We individually tracked each
      subject for a 5-year period from their index date to identify those who developed
      RA. A stratified Cox proportional hazard regression was performed to calculate
      the hazard ratio (HR) and its corresponding 95% confidence interval (CI) for the
      subsequent development of RA during the 5-year follow-up period between subjects
      who underwent an appendectomy and comparison subjects. Of the sampled subjects,
      93 (0.54%) received a diagnosis of RA during the 5-year follow-up period: 33 from
      the study cohort (0.77% of subjects who underwent an appendectomy) and 60 from
      the comparison cohort (0.47% of comparison subjects) (p<0.001). After censoring
      individuals who died during the follow-up period and adjusting for subjects'
      monthly income and geographic region, the HR of RA during the 5-year follow-up
      period was 1.61 (95% CI = 1.05~2.48) for subjects who underwent an appendectomy
      compared to comparison subjects. We found that among females, the adjusted HR of
      RA was 1.76 (95% CI = 1.04~2.96) for subjects who underwent an appendectomy
      compared to comparison subjects. However, there was no increased hazard of RA for
      males who underwent an appendectomy compared to comparison subjects. We concluded
      that female subjects who undergo an appendectomy have a higher risk of RA than
      comparison female subjects. 

PMID- 25970544
TI  - Syndecan-1 Acts in Synergy with Tight Junction Through Stat3 Signaling to
      Maintain Intestinal Mucosal Barrier and Prevent Bacterial Translocation.
AB  - BACKGROUND: Intestinal epithelial tight junction (TJ) is the principal
      determinant of mucosal permeability, defects of which have been correlated to
      inflammatory bowel disease. In this study, we investigated whether syndecan-1
      (Sdc1), the predominant cell surface heparan sulfate proteoglycan, affects TJ
      proteins to protect intestinal barrier function. METHODS: The role of Sdc1 in
      barrier function was examined in cultured colonic epithelial cells and dextran
      sodium sulfate-induced colitis mouse model. Barrier function was determined by
      transepithelial electrical resistance, bacterial translocation, and FITC-dextran
      flux. Canonical TJ proteins ZO-1 and occludin were measured by Western blot and
      immunofluoresence. Role of the Stat3 pathway was detected by Western blot and
      chromatin immunoprecipitation. RESULTS: Overexpressed Sdc1 in Caco-2 cells
      attenuated transepithelial electrical resistance reduction, prevented bacterial
      translocation, and repressed FITC-dextran flux, whereas Sdc1 knockdown in HT29
      cells resulted in a greater loss of barrier function. Supplementation of
      exogenous Sdc1 in colitis mice ameliorated the activity of colitis and barrier
      defect. Mechanistically, Sdc1 significantly modulated expressions of ZO-1 and
      occludin by activating Stat3, which directly bound to the promoter regions of ZO
      1 and occludin. Furthermore, ZO-1 and occludin were found to bind to each other,
      and their repression could induce Sdc1 upregulation. CONCLUSIONS: Sdc1 plays an
      important role in protecting the intestinal barrier function and preventing
      bacterial translocation, in synergy with TJ through Stat3 signaling in an
      Sdc1/Stat3/ZO-1 and occludin feedback loop. Sdc1 participates in the mechanism
      that is related to intestinal barrier function and colitis and represents a
      therapeutic target for novel anti-inflammatory bowel disease strategies.

PMID- 25970543
TI  - Immune response gene expression in colorectal cancer carries distinct prognostic
      implications according to tissue, stage and site: a prospective retrospective
      translational study in the context of a hellenic cooperative oncology group
      randomised trial.
AB  - BACKGROUND: Although host immune response is an emerging prognostic factor for
      colorectal cancer, there is no consensus on the optimal methodology, surrogate
      markers or tissue for study. PATIENTS AND METHODS: Tumour blocks were
      prospectively collected from 344 patients with stage II/III colorectal cancer
      (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration
      was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM,
      FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the
      centre of tumour, invasive margin and adjacent normal mucosa. RESULTS:
      Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%)
      mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene
      expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death
      1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05
      2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We
      used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS)
      and proceeded to partitioning analysis in 267 patients, with age, stage, tumour
      site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in
      patients with stage III right-sided colon cancer, a low immune response was
      associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95%
      CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other
      stage or site of CRC, or for a similar mIS score derived from adjacent normal
      mucosa. Independent adverse prognostic significance was retained in multivariable
      analysis for absence of necrosis, tumour ESR1 expression in all patients and low
      tumour mIS in stage III right-sided CRC. CONCLUSIONS: In localised CRC, mRNA
      based CD3Z/CD8 profiling of tumour immune response may have stage, site and
      tissue-specific prognostic significance, along with ESR1 expression. TRIAL
      REGISTRATION: ANZCTR.org.au ACTRN12610000509066.

PMID- 25970545
TI  - Comparative Effectiveness of Nutritional and Biological Therapy in North American
      Children with Active Crohn's Disease.
AB  - BACKGROUND: Therapeutic targets in pediatric Crohn's disease include symptoms,
      quality of life (QOL), and mucosal healing. Although partial enteral nutrition
      (PEN), exclusive enteral nutritional (EEN), and anti-tumor necrosis factor alpha
      (anti-TNF) therapy all improve symptoms, the comparative effectiveness of these
      approaches to improve QOL and achieve mucosal healing has not been assessed
      prospectively. METHODS: In a prospective study of children initiating PEN, EEN,
      or anti-TNF therapy for Crohn's disease, we compared clinical outcomes using the
      Pediatric Crohn's Disease Activity Index (PCDAI), QOL (IMPACT score), and mucosal
      healing as estimated by fecal calprotectin (FCP). PCDAI, IMPACT, FCP, and diet
      (prompted 24-h recall) were measured at baseline and after 8 weeks of therapy.
      RESULTS: We enrolled 90 children with active Crohn's disease (PCDAI, 33.7 +/-
      13.7; and FCP, 976 +/- 754), of whom 52 were treated with anti-TNF, 22 with EEN,
      and 16 with PEN plus ad lib diet. Clinical response (PCDAI reduction >=15 or
      final PCDAI <=10) was achieved by 64% on PEN, 88% EEN, and 84% anti-TNF (test for
      trend P = 0.08). FCP <=250 MUg/g was achieved with PEN in 14%, EEN 45%, and anti
      TNF 62% (test for trend P = 0.001). Improvement in overall QOL was not
      statistically significantly different between the 3 groups (P = 0.86). However,
      QOL improvement was the greatest with EEN in the body image (P = 0.03) domain and
      with anti-TNF in the emotional domain (P = 0.04). CONCLUSIONS: Although PEN
      improved clinical symptoms, EEN and anti-TNF were more effective for decreasing
      mucosal inflammation and improving specific aspects of QOL.

PMID- 25970546
TI  - Patterns and Predictors of Long-term Nonuse of Medical Therapy Among Persons with
      Inflammatory Bowel Disease.
AB  - BACKGROUND: To evaluate patterns and predictors of long-term nonuse of
      inflammatory bowel disease (IBD)-specific medications among patients with IBD.
      METHODS: All incident cases of IBD diagnosed between 1987 and 2012 were
      identified from the population-based University of Manitoba IBD Epidemiology
      Database. Point prevalence of long-term medication nonuse (defined as no receipt
      of IBD-specific medications for a year or longer) was determined over calendar
      time and the course of disease. Cox proportional hazard regression analysis was
      performed to identify factors associated with delayed initiation and with
      becoming a long-term nonuser. RESULTS: Among 6451 persons with IBD followed since
      1987 (46.8% male, 47.8% with Crohn's disease), 11.7% were not dispensed an IBD
      specific medication within the first year and 6.2% within 5 years after
      diagnosis. Factors associated with delayed initiation included having Crohn's
      disease (hazard ratio [HR] = 0.78, 95% confidence interval [CI], 0.73-0.83),
      lower socioeconomic status (HR = 0.91, 95% CI, 0.84-0.98), age more than 65 years
      (HR = 0.76, 95% CI, 0.67-0.86), and having any medical comorbidity. The
      prevalence of long-term nonuse consistently remained between 40% and 50% of
      persons with IBD across the study years. Patients with Crohn's disease (HR =
      1.14, 95% CI, 1.04-1.25), lower socioeconomic status (HR = 1.14, 95% CI, 1.02
      1.27), patients with IBD-associated surgery (HR = 1.72, 95% CI, 1.51-1.96), or
      delayed initiation of first IBD medication were more likely to become long-term
      nonusers after initiation. CONCLUSIONS: At any given time, roughly half of all
      patients with IBD have not used IBD-specific medications in the previous year.
      Further work is required to evaluate the clinical implications of long-term
      medication nonuse in IBD.

PMID- 25970548
TI  - Identification of gastric atrophic changes: from histopathology to endoscopy.
AB  - In an aging European population, an increasing number of individuals will suffer
      from gastric cancer in the coming two decades. Recent research has determined the
      risk for gastric cancer in patients with different stages of gastric atrophy.
      Based on these data, it is now recommended that surveillance is offered to
      individuals with advanced stages of atrophic gastritis. Endoscopic biopsies of
      the gastric antrum and corpus are recommended in order to assess the severity and
      extent of gastric atrophy. This enables identification of those at highest risk
      of progressing to cancer. However, systematic reviews have shown that in recent
      years many researchers have assessed new endoscopic technologies for their
      accuracy in determining the severity and extent of gastric atrophy and metaplasia
      without the use of histology. Simple, reliable and accurate endoscopic features
      have been identified that can be used to either target biopsies or avoid biopsy
      sampling in the absence of endoscopic features of atrophy and intestinal
      metaplasia. This may largely simplify everyday practice. Randomized trials or
      large observational studies are now needed to demonstrate the accuracy of
      endoscopic assessment of the entire gastric mucosa and its impact on patient
      management. 

PMID- 25970547
TI  - From hair to heart: nestin-expressing hair-follicle-associated pluripotent (HAP)
      stem cells differentiate to beating cardiac muscle cells.
AB  - We have previously demonstrated that the neural stem-cell marker nestin is
      expressed in hair follicle stem cells located in the bulge area which are termed
      hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse
      and human could form spheres in culture, termed hair spheres, which are keratin
      15-negative and CD34-positive and could differentiate to neurons, glia,
      keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we
      demonstrated that nestin-expressing stem cells could effect nerve and spinal cord
      regeneration in mouse models. In the present study, we demonstrated that HAP stem
      cells differentiated to beating cardiac muscle cells. We separated the mouse
      vibrissa hair follicle into 3 parts (upper, middle, and lower), and suspended
      each part separately in DMEM containing 10% FBS. All three parts of hair follicle
      differentiated to beating cardiac muscle cells as well as neurons, glial cells,
      keratinocytes and smooth muscle cells. The differentiation potential to cardiac
      muscle is greatest in the upper part of the follicle. The beat rate of the
      cardiac muscle cells was stimulated by isoproterenol and inhibited by propanolol.
      HAP stem cells have potential for regenerative medicine for heart disease as well
      as nerve and spinal cord repair.

PMID- 25970549
TI  - Reliability of the Spatiotemporal Determinants of Maximal Sprint Speed in
      Adolescent Boys Over Single and Multiple Steps.
AB  - The purpose of this study was to examine the reliability of the spatiotemporal
      determinants of maximal sprinting speed in boys over single and multiple steps.
      Fifty-four adolescent boys (age = 14.1 +/- 0.7 years [range = 12.9-15.7 years];
      height = 1.63 +/- 0.09 m; body mass = 55.3 +/- 13.3 kg; -0.31 +/- 0.90 age from
      Peak Height Velocity (PHV) in years; mean +/- s) volunteered to complete a 30 m
      sprint test on 3 occasions over a 2-week period. Speed, step length, step
      frequency, contact time, and flight time were assessed via an optical measurement
      system. Speed and step characteristics were obtained from the single-fastest step
      and average of the 2 and 4 fastest consecutive steps. Pairwise comparison of
      consecutive trials revealed the coefficient of variation (CV) for speed was
      greater in 4-step (CV = 7.3 & 7.5%) compared with 2-step (CV = 4.2 & 4.1%) and 1
      step (CV = 4.8 & 4.6%) analysis. The CV of step length, step frequency and
      contact time ranged from 4.8 to 7.5% for 1-step, 3.8-5.0% for 2-step and 4.2-7.5%
      for 4-step analyses across all trials. An acceptable degree of reliability was
      achieved for the spatiotemporal and performance variables assessed in this study.
      Two-step analysis demonstrated the highest degree of reliability for the key
      spatiotemporal variables, and therefore may be the most suitable approach to
      monitor the spatiotemporal characteristics of maximal sprint speed in boys. 

PMID- 25970550
TI  - A bioinspired soft manipulator for minimally invasive surgery.
AB  - This paper introduces a novel, bioinspired manipulator for minimally invasive
      surgery (MIS). The manipulator is entirely composed of soft materials, and it has
      been designed to provide similar motion capabilities as the octopus's arm in
      order to reach the surgical target while exploiting its whole length to actively
      interact with the biological structures. The manipulator is composed of two
      identical modules (each of them can be controlled independently) with multi
      directional bending and stiffening capabilities, like an octopus arm. In the
      authors' previous works, the design of the single module has been addressed. Here
      a two-module manipulator is presented, with the final aim of demonstrating the
      enhanced capabilities that such a structure can have in comparison with rigid
      surgical tools currently employed in MIS. The performances in terms of workspace,
      stiffening capabilities, and generated forces are characterized through
      experimental tests. The combination of stiffening capabilities and manipulation
      tasks is also addressed to confirm the manipulator potential employment in a real
      surgical scenario. 

PMID- 25970551
TI  - Influence of Surface Chemistry on the Release of an Antibacterial Drug from
      Nanostructured Porous Silicon.
AB  - Nanostructured mesoporous silicon possesses important properties advantageous to
      drug loading and delivery. For controlled release of the antibacterial drug
      triclosan, and its associated activity versus Staphylococcus aureus, previous
      studies investigated the influence of porosity of the silicon matrix. In this
      work, we focus on the complementary issue of the influence of surface chemistry
      on such properties, with particular regard to drug loading and release kinetics
      that can be ideally adjusted by surface modification. Comparison between drug
      release from as-anodized, hydride-terminated hydrophobic porous silicon and the
      oxidized hydrophilic counterpart is complicated due to the rapid bioresorption of
      the former; hence, a hydrophobic interface with long-term biostability is
      desired, such as can be provided by a relatively long chain octyl moiety. To
      minimize possible thermal degradation of the surfaces or drug activity during
      loading of molten drug species, a solution loading method has been investigated.
      Such studies demonstrate that the ability of porous silicon to act as an
      effective carrier for sustained delivery of antibacterial agents can be
      sensitively altered by surface functionalization. 

PMID- 25970552
TI  - Differences in Regional Brain Volumes Two Months and One Year after Mild
      Traumatic Brain Injury.
AB  - Conventional structural imaging is often normal after mild traumatic brain injury
      (mTBI). There is a need for structural neuroimaging biomarkers that facilitate
      detection of milder injuries, allow recovery trajectory monitoring, and identify
      those at risk for poor functional outcome and disability. We present a novel
      approach to quantifying volumes of candidate brain regions at risk for injury.
      Compared to controls, patients with mTBI had significantly smaller volumes in
      several regions including the caudate, putamen, and thalamus when assessed 2
      months after injury. These differences persisted but were reduced in magnitude 1
      year after injury, suggesting the possibility of normalization over time in the
      affected regions. More pronounced differences, however, were found in the
      amygdala and hippocampus, suggesting the possibility of regionally specific
      responses to injury. 

PMID- 25970553
TI  - The impact of cell phone use on the intensity and liking of a bout of treadmill
      exercise.
AB  - This study used a within-subjects design to assess the effect of three common
      cellular telephone (cell phone) functions (texting, talking, listening to music)
      on planned exercise. Forty-four young adults (n = 33 females, 21.8 +/- 1.3 years)
      each participated in four, separate, 30-minute exercise conditions on a treadmill
      in a random order. During each condition, the treadmill speed display was covered
      and grade was fixed at zero. However, participants were able to alter treadmill
      speed as desired. Throughout the texting and talking conditions, research
      personnel used a pre-determined script to simulate cell phone conversations.
      During the music condition, participants used their cell phone to listen to music
      of their choice. Finally, participants completed a control condition with no cell
      phone access. For each condition, average treadmill speed, heart rate and liking
      (via visual analog scale) were assessed. Treadmill speed (3.4 +/- 1.3 miles?hour(
      1)), heart rate (122.3 +/- 24.3 beats?min(-1)) and liking (7.5 +/- 1.5 cm) in the
      music condition were significantly (p <= 0.014) greater than all other
      conditions. Treadmill speed in the control condition (3.1 +/- 1.2 miles?hour(-1))
      was significantly (p = 0.04) greater than both texting and talking (2.8 +/- 1.1
      miles?hour(-1) each). Heart rate during the control condition (115.4 +/- 22.8
      beats?min(-1)) was significantly (p = 0.04) greater than texting (109.9 +/- 16.4
      beats?min(-1)) but not talking (112.6 +/- 16.1 beats?min(-1)). Finally, liking
      during the talking condition (5.4 +/- 2.2 cm) was greater (p = 0.05) than the
      control (4.3 +/- 2.2 cm) but not the texting (5.1 +/- 2.2 cm) conditions. In
      conclusion, using a cell phone for listening to music can increase the intensity
      (speed and heart rate) and liking of a bout of treadmill exercise. However, other
      common cell phone uses (texting and talking) can interfere with treadmill
      exercise and reduce intensity.

PMID- 25970554
TI  - Essential thrombocythemia with Mpl W515 K mutation in a child presenting with
      Budd-Chiari syndrome.
AB  - Essential thrombocythemia (ET) is an extremely rare childhood disorder
      characterised by clonal expansion of megakaryocytic lineage in bone marrow,
      leading to a persistent increase in the number of circulating thrombocytes and
      thus increased risk for thrombotic and haemorrhagic events. The molecular
      mechanisms of ET are not fully understood. Most children with ET have the JAK2
      V617F somatic mutation; however, another mutation, involving a W to L or K
      substitution at Mpl codon 515, was reported in a small proportion of adult ET
      patients that is extremely rare in children. Herein, we describe a Mpl W515K
      somatic mutation in a paediatric case of ET who presented with Budd-Chiari
      syndrome. No paediatric patient harbouring a Mpl W515K mutation has been
      previously reported. 

PMID- 25970555
TI  - Comedonal and Cystic Fibrofolliculomas in Birt-Hogg-Dube Syndrome.
AB  - IMPORTANCE: The differential diagnosis of extensive open comedones includes
      inherited genetic syndromes and several acquired conditions. Birt-Hogg-Dube
      syndrome (BHD) is not typically included in the differential diagnosis of
      syndromes with comedonal lesions. Given the potentially life-threatening systemic
      complications associated with BHD, early recognition and diagnosis of the
      condition is important. OBSERVATIONS: We describe comedonal or cystic
      fibrofolliculomas in 4 patients with BHD. Cutaneous lesions were identified on
      the face, neck, chest, and abdomen. CONCLUSIONS AND RELEVANCE: Comedonal or
      cystic fibrofolliculomas are a variant of fibrofolliculomas that have not
      previously been well characterized in patients with BHD and represent a novel
      diagnostic clue to its early detection and diagnosis. Expanding the phenotypic
      features of BHD facilitates earlier diagnosis of the syndrome, which allows for
      early surveillance of renal cancer in affected patients as well as disease
      screening in their relatives.

PMID- 25970556
TI  - Palladium(II) Complex of a Redox-Active Amidophenolate-Based O,N,S,N Ligand: Its
      Monocation and Dication and Reactivity with PPh3.
AB  - A new potentially tetradentate redox-active o-aminophenol-based ligand, H2L = 2
      (2-ethylthio)pyridine-anilino-4,6-di-tert-butylphenol, reacts with
      Pd(II)(O2CCH3)2 in CH3OH in the presence of air and Et3N affording isolation of a
      green crystalline solid of composition [Pd(L)] 1. When examined by cyclic
      voltammetry (CV), 1 exhibits two quasireversible oxidative responses at E1/2 =
      0.16 (peak-to-peak separation, DeltaEp = 100 mV) and 0.89 V (DeltaEp = 90 mV) vs
      SCE (saturated calomel electrode). Chemical oxidation of 1 by [Fe(III)(eta(5)
      C5H5)2][PF6] and AgBF4 in CH2Cl2 led to the isolation of two crystalline solids,
      red [Pd(L)][PF6].CH2Cl2 2 and dark green [Pd(L)][BF4]2.2CH2Cl2 3, respectively.
      Single-crystal X-ray crystallography at 100(2) K unambiguously established that
      the O,N,S,N-coordinated ligand is present in the square-planar complexes
      [Pd(II){(L(AP))(2-)}] 1, [Pd(II){(L(ISQ))(*-)}][PF6].CH2Cl2 2, and
      [Pd(II){(L(IBQ))(0)}][BF4]2.2CH2Cl2 3, as dianionic (L(AP))(2-), monoanionic o
      iminobenzosemiquinonate(1-) pi-radical (Srad = (1)/2) (L(ISQ))(*-), and neutral o
      iminobenzoquinone (L(IBQ))(0) redox level. Reaction of 1 and 2 with PPh3 afforded
      isolation of two crystalline complexes: dark green [Pd(II)(L)(PPh3)] 4 and red
      [Pd(II){(L(ISQ))(*-)}(PPh3)][PF6].CH2Cl2 5. X-ray structure determination of 5 at
      100(2) K revealed Pd(II)ON2P coordination environment. The square-planar
      complexes 1-5 possess an S = 0, (1)/2, 0, 0, and (1)/2 ground-state,
      respectively, as was established by (1)H NMR and EPR spectroscopy, and room
      temperature magnetic moment data. All redox processes are thus shown to be ligand
      based. Absorption spectral measurements were done for all complexes. DFT
      calculations at B3LYP-level of theory adequately describe the electronic
      structures of 1-3, and 5, containing a spin-paired d(8) Pd(II) ion. Time
      dependent-DFT calculations on 1-3 and 5 shed light on the origin of UV-vis-NIR
      spectral absorptions. 

PMID- 25970557
TI  - Conformational plasticity surrounding the active site of NADH oxidase from
      Thermus thermophilus.
AB  - Biotechnological applications of enzymes can involve the use of these molecules
      under nonphysiological conditions. Thus, it is of interest to understand how
      environmental variables affect protein structure and dynamics and how this
      ultimately modulates enzyme function. NADH oxidase (NOX) from Thermus
      thermophilus exemplifies how enzyme activity can be tuned by reaction conditions,
      such as temperature, cofactor substitution, and the addition of cosolutes. This
      enzyme catalyzes the oxidation of reduced NAD(P)H to NAD(P)(+) with the
      concurrent reduction of O2 to H2O2, with relevance to biosensing applications. It
      is thermophilic, with an optimum temperature of approximately 65 degrees C and
      sevenfold lower activity at 25 degrees C. Moderate concentrations (~1M) of urea
      and other chaotropes increase NOX activity by up to a factor of 2.5 at room
      temperature. Furthermore, it is a flavoprotein that accepts either FMN or the
      much larger FAD as cofactor. We have used nuclear magnetic resonance (NMR)
      titration and (15)N spin relaxation experiments together with isothermal
      titration calorimetry to study how NOX structure and dynamics are affected by
      changes in temperature, the addition of urea and the substitution of the FMN
      cofactor with FAD. The majority of signals from NOX are quite insensitive to
      changes in temperature, cosolute addition, and cofactor substitution. However, a
      small cluster of residues surrounding the active site shows significant changes.
      These residues are implicated in coupling changes in the solution conditions of
      the enzyme to changes in catalytic activity.

PMID- 25970560
TI  - Conductivity-limiting bipolar thermal conductivity in semiconductors.
AB  - Intriguing experimental results raised the question about the fundamental
      mechanisms governing the electron-hole coupling induced bipolar thermal
      conduction in semiconductors. Our combined theoretical analysis and experimental
      measurements show that in semiconductors bipolar thermal transport is in general
      a "conductivity-limiting" phenomenon, and it is thus controlled by the carrier
      mobility ratio and by the minority carrier partial electrical conductivity for
      the intrinsic and extrinsic cases, respectively. Our numerical method quantifies
      the role of electronic band structure and carrier scattering mechanisms. We have
      successfully demonstrated bipolar thermal conductivity reduction in doped
      semiconductors via electronic band structure modulation and/or preferential
      minority carrier scatterings. We expect this study to be beneficial to the
      current interests in optimizing thermoelectric properties of narrow gap
      semiconductors. 

PMID- 25970561
TI  - Antiviral Activity of Diterpene Esters on Chikungunya Virus and HIV Replication.
AB  - Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated
      from various Euphorbiaceae species, of which some have been shown to be potent
      inhibitors of chikungunya virus (CHIKV) replication. To further explore this type
      of compound, the antiviral activity of a series of 29 commercially available
      natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be
      the most potent inhibitor, with an EC50 value of 6.0 +/- 0.9 nM and a selectivity
      index (SI) of 686, which is in line with the previously reported anti-CHIKV
      potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13).
      Most of the other compounds exhibited low to moderate activity, including an
      ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 +/- 0.1 MUM
      and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so
      the antiviral activities of compounds 1-29 were evaluated also against HIV-1 and
      HIV-2. Tigliane- (4beta-hydroxyphorbol analogues 10, 11, 13, 15, 16, and 18) and
      ingenane-type (27 and 28) diterpene esters were shown to inhibit HIV replication
      in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV
      and anti-HIV data sets demonstrated a linear relationship, which supported the
      hypothesis made that PKC may be an important target in CHIKV replication. 

PMID- 25970559
TI  - Optimizing Polychlorinated Biphenyl Degradation by Flavonoid-Induced Cells of the
      Rhizobacterium Rhodococcus erythropolis U23A.
AB  - There is evidence that many plant secondary metabolites may act as signal
      molecules to trigger the bacterial ability to metabolize polychlorinated
      biphenyls (PCBs) during the rhizoremediation process. However, the bases for the
      PCB rhizoremediation process are still largely unknown. The rhizobacterium
      Rhodococcus erythropolis U23A is unable to use flavanone as a growth substrate.
      However, on the basis of an assay that monitors the amount of 4-chlorobenzoate
      produced from 4-chlorobiphenyl by cells grown co-metabolically on flavanone plus
      sodium acetate, this flavonoid was previously found to be a potential inducer of
      the U23A biphenyl catabolic pathway. In this work, and using the same assay, we
      identified ten other flavonoids that did not support growth, but that acted as
      inducers of the U23A biphenyl pathway, and we confirmed flavonoid induction of
      the biphenyl catabolic pathway using quantitative real-time polymerase chain
      reaction (RT-qPCR) on the bphA gene. We also examined the effect of the growth co
      substrate on flavonoid induction. Sodium acetate was replaced by glucose,
      mannose, sucrose, or mannitol, which are sugars found in plant root exudates. The
      data showed that the level of induction of strain U23A biphenyl-degrading enzymes
      was significantly influenced by the nature and concentration of the flavonoid in
      the growth medium, as well as by the substrate used for growth. Sucrose allowed
      for an optimal induction response for most flavonoids. Some flavonoids, such as
      flavone and isoflavone, were better inducers of the biphenyl catabolic enzymes
      than biphenyl itself. We also found that all flavonoids tested in this work were
      metabolized by strain U23A during co-metabolic growth, but that the metabolite
      profiles, as well as the level of efficiency of degradation, differed for each
      flavonoid. To obtain insight into how flavonoids interact with strain U23A to
      promote polychlorinated biphenyl (PCB) degradation, we determined the
      concentration of flavanone at which optimal PCB-degrading performance of strain
      U23A was achieved. We showed that it corresponded to the concentration required
      to fully induce the biphenyl catabolic pathway of the strain. Together, our data
      demonstrate that optimal PCB degradation during the rhizoremediation process will
      require the adjustment of several parameters, including the presence of the
      appropriate flavonoids at the proper concentrations and the presence of proper
      growth substrates that positively influence the ability of flavonoids to induce
      the pathway. 

PMID- 25970558
TI  - New roles for mitochondrial proteases in health, ageing and disease.
AB  - Recent advances in mitochondrial biology have revealed the high diversity and
      complexity of proteolytic enzymes that regulate mitochondrial function. We have
      classified mitochondrial proteases, or mitoproteases, on the basis of their
      function and location, and defined the human mitochondrial degradome as the
      complete set of mitoproteases that are encoded by the human genome. In addition
      to their nonspecific degradative functions, mitoproteases perform highly
      regulated proteolytic reactions that are important in mitochondrial function,
      integrity and homeostasis. These include protein synthesis, quality control,
      mitochondrial biogenesis and dynamics, mitophagy and apoptosis. Impaired or
      dysregulated function of mitoproteases is associated with ageing and with many
      pathological conditions such as neurodegenerative disorders, metabolic syndromes
      and cancer. A better understanding of the mitochondrial proteolytic landscape and
      its modulation may contribute to improving human lifespan and 'healthspan'. 

PMID- 25970562
TI  - A novel sound-blocking structure based on the muffler principle for rib-sparing
      transcostal high-intensity focused ultrasound treatment.
AB  - The main challenge in transcostal high-intensity focused ultrasound therapy is
      minimising heat deposition in the ribs while ensuring that a sufficient dose is
      delivered to the target region. Current approaches rely on expensive multichannel
      phased-array systems to turn the individual transducer on and off according to
      either geometrical arrangements or complicated wave calculations. To protect the
      ribs from heating, the ultrasound energy must not only not reach the ribs, but
      must also not accumulate in front of the ribs. The research in this paper
      proposes a different approach, of attaching a sound-blocking structure in front
      of the rib cage with similar effects to those of an engine exhaust muffler. The
      sound-blocking structure is based on the muffler principle to prevent ultrasound
      energy from reaching the ribs and reduce the amount of energy reflected back to
      the applicator. Finite element simulations with a 0.5-MHz transducer of the
      overall sound fields and temperature distribution showed that the ultrasound
      pressure and energy level would decrease behind the novel sound-blocking
      structures, thereby resulting in a lower temperature at the ribs than at the
      tumour. Without the protecting structure, the rib temperature reached 104.19 
      degrees C whereas with the structure it reached only 37.86  degrees C. An
      experimental set-up using porcine ribs with a phantom was also developed to
      validate the concept, which showed that the rib temperature reached 73  degrees C
      without protection within 1 min of ablation time whereas it reached 36.5  degrees
      C with the device. The tumour region in the tests reached 51  degrees C and 49 
      degrees C with and without protection, respectively. 

PMID- 25970563
TI  - Age-dependency of glycosaminoglycan content in lumbar discs: A 3t gagcEST study.
AB  - PURPOSE: To analyze age-dependency of glycosaminoglycan content using gagCEST
      (glycosaminoglycan chemical exchange saturation transfer) imaging in lumbar
      intervertebral discs of healthy volunteers. MATERIALS AND METHODS: In all, 70
      volunteers without low back pain (mean age 44 +/- 14 years, range: 21-69 years)
      were examined with T2 -weighted and gagCEST imaging with a 3T MR scanner, with
      approval of the local Ethics Committee after written informed consent was
      obtained. Pfirrmann grading and classification into discs without bulging and
      herniation, discs with bulging, and discs with herniation were performed. Only
      intervertebral discs without bulging and herniation were analyzed. A region-of
      interest-based gagCEST analysis of nucleus pulposus (NP) and annulus fibrosus
      (AF) was performed. Correlation between age and gagCEST was tested within groups
      of equal Pfirrmann score. RESULTS: GagCEST effects decreased significantly from
      3.09 +/- 1.12% in 20-29 years old volunteers to -0.24 +/- 1.36% in 50-59 years
      old volunteers (P < 0.001). In the case of Pfirrmann scores 2 and 3, a
      significant correlation was observed between gagCEST effect and age (Pfirrmann
      score 2, NP: rho = -0.558, P < 0.001; Pfirrmann score 3, NP: rho = -0.337, P =
      0.048). For Pfirrmann scores 1 and 4, no significant correlation was obtained
      (Pfirrmann score 1, NP: rho = -0.046, P = 0.824; Pfirrmann score 4, NP: rho = 
      0.316, P = 0.188). CONCLUSION: We show a decreased gagCEST effect likely
      corresponding to decreasing glycosaminoglycans with aging. Hence, age-matched
      analysis of gagCEST imaging may be necessary in future studies.

PMID- 25970564
TI  - Preparation and release behavior of chlorpyrifos adsolubilized into layered zinc
      hydroxide nitrate intercalated with dodecylbenzenesulfonate.
AB  - A novel method was developed to make the charge-neutral and poorly water-soluble
      pesticide chlorpyrifos (CPF) adsolubilize into layered zinc hydroxide nitrate
      intercalated with dodecylbenzenesulfonate (ZHN-DBS). It included two steps:
      first, CPF was solubilized into the micelles formed by anionic surfactant sodium
      dodecylbenzenesulfonate (DBS), nonionic surfactant polyoxyethylene (10) nonyl
      phenyl ether (TX-10) or zwitterionic surfactant dodecyl betaine (DB), and then
      ZHN-DBS was poured into CPF micelles to synthesize ZHN-DBS-CPF, ZHN-TX-10-CPF,
      and ZHN-DB-CPF intercalated compounds. These intercalated compounds were
      characterized by powder X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FT-IR), and thermogravimetric analysis and differential thermal
      analysis (TGA/DTA). The results showed that ZHN-DBS-CPF, ZHN-TX-10-CPF, and ZHN
      DB-CPF had the basal spacings of 3.29-3.59, 2.57-2.87, and 1.97 nm, respectively,
      which was discussed from the intercalated mechanism. The intercalated CPF had the
      higher thermal stability. Release behaviors of CPF from intercalated compounds
      were investigated and analyzed in buffer solutions (pH 5.0 and 6.8). The results
      exhibited that the release rates and equilibrium release amounts of CPF were
      closely dependent on micelles types and release mediums. The release behaviors of
      ZHN-DBS-CPF and ZHN-TX-10-CPF were well described with pseudo second-order and
      parabolic diffusion models. The present study suggested that ZHN-DBS-CPF and ZHN
      TX-10-CPF could be applied as a potential pesticide delivery system. 

PMID- 25970565
TI  - Correction: interleukin 21 signaling in B cells is required for efficient
      establishment of murine gammaherpesvirus latency.

PMID- 25970566
TI  - In pursuit of resolution in time-of-flight mass spectrometry: A historical
      perspective.
AB  - Time-of-flight mass spectrometry is reviewed from its inception in the 1940s to
      the present day. The review is concerned with fundamentals of time-of-flight
      analyzers and of ion sources to the extent that sources influence analyzers. The
      patent literature has been covered, and efforts made to bring to light less well
      known papers and studies (c) 2015 Wiley Periodicals, Inc. Mass Spec Rev. 35:738
      757, 2016.

PMID- 25970567
TI  - Leg cramps.
AB  - INTRODUCTION: Involuntary, localised leg cramps are common and typically affect
      the calf muscles at night. METHODS AND OUTCOMES: We conducted a systematic review
      and aimed to answer the following clinical questions: What are the effects of
      treatments for idiopathic leg cramps? What are the effects of treatments for leg
      cramps in pregnancy? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to January 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 16 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:
      analgesics; anti-epileptic drugs; calcium salts; diltiazem; magnesium salts;
      multivitamin and mineral supplements; quinine; sodium chloride; stretching
      exercises; verapamil; vitamin B6 (pyridoxine); and vitamin E.

PMID- 25970568
TI  - Adherence in orthodontic settings: understanding practitioner views in a UK
      sample.
AB  - OBJECTIVE: To explore predictors of adherence in adult orthodontic patients as
      reported by orthodontists in the UK. MATERIALS AND METHODS: Twenty-three
      orthodontists (47% female and 53% male) from the UK with approximately 15 years
      of experience each (M  =  14.7; SD  =  1.73) completed a questionnaire regarding
      the importance they give to a number of factors signaled in the literature as
      adequate predictors of adherence. This cross-sectional quantitative and
      exploratory survey consisted of four parts, requesting orthodontists to rate a
      list of predictors of adherence on (1) evaluation-how important they thought the
      predictor was to assess patient adherence, (2) application-the extent to which
      they used each predictor to assess adherence in their daily practice, (3) open
      ended questions to collect any other perceived predictors of adherence, and (4)
      demographics. RESULTS: All participating orthodontists agreed that patients'
      regularity in attending appointments, maintenance of good oral hygiene, and
      utilization of dental appliances are the most important factors for predicting
      adherence. In the open-ended portion of the questionnaire, orthodontists also
      highlighted perceived cost of treatment as an important factor. The remaining
      factors included in the questionnaire were also rated as important or utilized,
      though they yielded a more varied pattern of response. CONCLUSIONS: Appointment
      keeping, cooperating in the use of removable appliances, and oral hygiene were
      rated as the most important factors by orthodontists when assessing adherence in
      adult patients. The perceived cost of treatment was also highlighted by
      orthodontists as an important factor for adherence.

PMID- 25970569
TI  - Lignin-assisted exfoliation of molybdenum disulfide in aqueous media and its
      application in lithium ion batteries.
AB  - In this article, alkali lignin (AL)-assisted direct exfoliation of MoS2 mineral
      into single-layer and few-layer nanosheets in water is reported for the first
      time. Under optimized conditions, the concentration of MoS2 nanosheets in the
      obtained dispersion can be as high as 1.75 +/- 0.08 mg mL(-1), which is much
      higher than the typical reported concentrations (<1.0 mg mL(-1)) using synthetic
      polymers or compounds as surfactants. The stabilizing mechanism primarily lies in
      the electrostatic repulsion between negative charged AL, as suggested by zeta
      potential measurements. When the exfoliated MoS2 nanosheets are applied as
      electrode materials for lithium ion batteries, they show much improved
      electrochemical performance compared with the pristine MoS2 mineral because of
      the enhanced ion and electron transfer kinetics. This facile, scalable and eco
      friendly aqueous-based process in combination with renewable and ultra-low-cost
      lignin opens up possibilities for large-scale fabrication of MoS2-based
      nanocomposites and devices. Moreover, herein we demonstrate that AL is also an
      excellent surfactant for exfoliation of many other types of layered materials,
      including graphene, tungsten disulfide and boron nitride, in water, providing
      rich opportunities for a wider range of applications. 

PMID- 25970570
TI  - Helical TiO2 Nanotube Arrays Modified by Cu-Cu2O with Ultrahigh Sensitivity for
      the Nonenzymatic Electro-oxidation of Glucose.
AB  - A novel Cu-Cu2O/TiO2/Ti electrode for the nonenzymatic electro-oxidation of
      glucose has been fabricated by secondary anodic oxidation combined with the
      electrodeposition method. It represents a new type of copper oxide-TiO2 complex
      nanostructure that demonstrates a new application. At the potential range from 
      1.0 to -1.6 V, Cu2+ was electrochemically reduced to Cu2O, accompanied by the
      simultaneous formation of Cu covering the top surface of the TiO2 nanotubes. The
      highest response current was obtained at the optimized fabrication conditions
      with a deposition charge of 1.5 C, a pH of 12, 4 mM CuSO4, and a deposition
      potential of -1.4 V. The results indicate that Cu2O helps to keep a broad linear
      range, and the incorporation of Cu nanoparticles improves the response current
      and sensitivity. The linearity between the response current and the glucose
      concentration was obtained in the range from 0.1 to 2.5 mM with a sensitivity of
      4895 MUA cm(-2) mM(-1). Such high sensitivity was attributed to the synergistic
      effect of the small Cu-Cu2O grain size and the large surface area of the helical
      TiO2 nanotube arrays as well as the fast electron transfer. Electrochemical
      impedance spectroscopy has been successfully applied to explain the differences
      among different electrode interfaces and the change rule of nonenzymatic electro
      oxidation properties.

PMID- 25970571
TI  - Polyacetylenes from carrots (Daucus carota) improve glucose uptake in vitro in
      adipocytes and myotubes.
AB  - A dichloromethane (DCM) extract of carrot roots was found to stimulate insulin
      dependent glucose uptake (GU) in adipocytes in a dose dependent manner. Bioassay
      guided fractionation of the DCM extract resulted in the isolation of the
      polyacetylenes falcarinol and falcarindiol. Both polyacetylenes were able to
      significantly stimulate basal and/or insulin-dependent GU in 3T3-L1 adipocytes
      and porcine myotube cell cultures in a dose-dependent manner. Falcarindiol
      increased peroxisome proliferator-activated receptor (PPAR)gamma-mediated
      transactivation significantly at concentrations of 3, 10 and 30 MUM, while
      PPARgamma-mediated transactivation by falcarinol was only observed at 10 MUM.
      Docking studies accordingly indicated that falcarindiol binds to the ligand
      binding domain of PPARgamma with higher affinity than falcarinol and that both
      polyacetylenes exhibit characteristics of PPARgamma partial agonists. Falcarinol
      was shown to inhibit adipocyte differentiation as evident by gene expression
      studies and Oil Red O staining, whereas falcarindiol did not inhibit adipocyte
      differentiation, which indicates that these polyacetylenes have distinct modes of
      action. The results of the present study suggest that falcarinol and falcarindiol
      may represent scaffolds for novel partial PPARgamma agonists with possible
      antidiabetic properties.

PMID- 25970573
TI  - From Evidence-based Medicine to Evidence-based Management (and Policy)?

PMID- 25970572
TI  - A de novo floral transcriptome reveals clues into Phalaenopsis orchid flower
      development.
AB  - Phalaenopsis has a zygomorphic floral structure, including three outer tepals,
      two lateral inner tepals and a highly modified inner median tepal called labellum
      or lip; however, the regulation of its organ development remains unelucidated. We
      generated RNA-seq reads with the Illumina platform for floral organs of the
      Phalaenopsis wild-type and peloric mutant with a lip-like petal. A total of
      43,552 contigs were obtained after de novo assembly. We used differentially
      expressed gene profiling to compare the transcriptional changes in floral organs
      for both the wild-type and peloric mutant. Pair-wise comparison of sepals, petals
      and labellum between peloric mutant and its wild-type revealed 1,838, 758 and
      1,147 contigs, respectively, with significant differential expression. PhAGL6a
      (CUFF.17763), PhAGL6b (CUFF.17763.1), PhMADS1 (CUFF.36625.1), PhMADS4
      (CUFF.25909) and PhMADS5 (CUFF.39479.1) were significantly upregulated in the lip
      like petal of the peloric mutant. We used real-time PCR analysis of lip-like
      petals, lip-like sepals and the big lip of peloric mutants to confirm the five
      genes' expression patterns. PhAGL6a, PhAGL6b and PhMADS4 were strongly expressed
      in the labellum and significantly upregulated in lip-like petals and lip-like
      sepals of peloric-mutant flowers. In addition, PhAGL6b was significantly
      downregulated in the labellum of the big lip mutant, with no change in expression
      of PhAGL6a. We provide a comprehensive transcript profile and functional analysis
      of Phalaenopsis floral organs. PhAGL6a PhAGL6b, and PhMADS4 might play crucial
      roles in the development of the labellum in Phalaenopsis. Our study provides new
      insights into how the orchid labellum differs and why the petal or sepal converts
      to a labellum in Phalaenopsis floral mutants. 

PMID- 25970575
TI  - An administrative claims measure of payments made for Medicare patients for a 30
      day episode of care for acute myocardial infarction.
AB  - BACKGROUND: Understanding both cost and quality across institutions is a critical
      first step to illuminating the value of care purchased by Medicare. Under
      contract with the Centers for Medicare and Medicaid Services, we developed a
      method for profiling hospitals by 30-day episode-of-care costs (payments for
      Medicare beneficiaries) for acute myocardial infarction (AMI). METHODS: We
      developed a hierarchical generalized linear regression model to calculate
      hospital risk-standardized payment (RSP) for a 30-day episode for AMI. Using 2008
      Medicare claims, we identified hospitalizations for patients 65 years of age or
      older with a discharge diagnosis of ICD-9 codes 410.xx. We defined an AMI episode
      as the date of admission plus 30 days. To reflect clinical care, we omitted or
      averaged payment adjustments for geographic factors and policy initiatives. We
      risk-adjusted for clinical variables identified in the 12 months preceding and
      including the AMI hospitalization. Using combined 2008-2009 data, we assessed
      measure reliability using an intraclass correlation coefficient and calculated
      the final RSP. RESULTS: The final model included 30 variables and resulted in
      predictive ratios (average predicted payment/average total payment) close to 1.
      The intraclass correlation coefficient score was 0.79. Across 2382 hospitals with
      >= 25 hospitalizations, the unadjusted mean payment was $20,324 ranging from
      $11,089 to $41,897. The mean RSP was $21,125 ranging from $13,909 to $28,979.
      CONCLUSIONS: This study introduces a claims-based measure of RSP for an AMI 30
      day episode of care. The RSP varies among hospitals, with a 2-fold range in
      payments. When combined with quality measures, this payment measure will help
      profile high-value care.

PMID- 25970574
TI  - Do Adult Medicaid Enrollees Prefer Going to Their Primary Care Provider's Clinic
      Rather Than Emergency Department (ED) for Low Acuity Conditions?
AB  - BACKGROUND: The rates of annual visits for adult Medicaid enrollees to the
      emergency department (ED) are increasing. Many programs throughout the country
      are focused on engaging patients in the use of their primary care providers (PCP)
      rather than the ED for low acuity conditions. It is unclear, however, the
      proportion of patients who are willing to use primary care services rather than
      the ED if they are given the choice. METHODS: Cross-sectional study of adult
      Medicaid enrollees (18 y and older) presenting to a large, urban, academic ED
      from June to August 2012 with a low acuity condition was performed. We excluded
      patients who did not have a PCP or active Medicaid insurance. Our primary goal
      was to determine the proportion of patients who prefer to use the ED, rather than
      their PCP clinic, if an appointment was immediately available. Our second goal
      was to understand why patients would prefer ED over PCP care. RESULTS: A total of
      150 patients agreed to complete the survey, and 95 (63.3%) met our inclusion
      criteria. Forty-three patients (45.3%) stated preferring to use their PCPs rather
      than the ED if an appointment was available at that time. Thirteen (48.1%) cited
      that the ED had more technology or specialty care services available when
      compared with their PCP's clinic, 8 (15.4%) were in significant pain, and 6
      (11.5%) felt the care they received in the ED was better than what they would
      receive in their PCP clinic. CONCLUSIONS: Our study shows that a little less than
      half of adult Medicaid enrollees presenting to the ED with low acuity conditions
      would have preferred to use their PCP rather than the ED, if an appointment had
      been immediately available.

PMID- 25970577
TI  - Correction: The GATA Factor elt-1 Regulates C. elegans Developmental Timing by
      Promoting Expression of the let-7 Family MicroRNAs.

PMID- 25970576
TI  - Psychometric properties of the Dutch version of the Attitude Towards Deliberate
      Self-Harm Questionnaire.
AB  - The attitude of nurses and treatment staff is crucial in the treatment of
      patients who self-harm. However, many patients experience that attitude as
      negative. The aim of this study was to investigate the psychometric properties of
      the Dutch version of the Attitude Towards Deliberate Self-Harm Questionnaire. A
      total of 261 questionnaires were used to measure validity and reliability.
      Sensitivity to change was measured using a post-test measurement (n = 171) and a
      subgroup of 78 participants were given the questionnaire twice for test-retest
      measurement. Factor analysis revealed four factors explaining 33% of the
      variance. Cronbach's alpha values ranged 0.585-0.809, with 0.637 for the total
      scale. Intraclass correlation coefficient was assessed in order to estimate test
      retest reliability, revealing the questionnaire was stable over time; the
      exception was factor 3, which had a value of 0.63. Sensitivity to change was
      found for the total score, factor one and two, and for three of the five items of
      factor three. We conclude that the Dutch version of the Attitude Towards
      Deliberate Self-Harm Questionnaire possesses adequate psychometric properties and
      is potentially an acceptable instrument for measuring the attitude of nurses and
      health-care staff towards patients who self-harm in Dutch-speaking countries.

PMID- 25970578
TI  - A novel method to analyze social transmission in chronologically sequenced
      assemblages, implemented on cultural inheritance of the art of cooking.
AB  - Here we present an analytical technique for the measurement and evaluation of
      changes in chronologically sequenced assemblages. To illustrate the method, we
      studied the cultural evolution of European cooking as revealed in seven cook
      books dispersed over the past 800 years. We investigated if changes in the set of
      commonly used ingredients were mainly gradual or subject to fashion fluctuations.
      Applying our method to the data from the cook books revealed that overall, there
      is a clear continuity in cooking over the ages--cooking is knowledge that is
      passed down through generations, not something (re-)invented by each generation
      on its own. Looking at three main categories of ingredients separately (spices,
      animal products and vegetables), however, disclosed that all ingredients do not
      change according to the same pattern. While choice of animal products was very
      conservative, changing completely sequentially, changes in the choices of spices,
      but also of vegetables, were more unbounded. We hypothesize that this may be due
      a combination of fashion fluctuations and changes in availability due to contact
      with the Americas during our study time period. The presented method is also
      usable on other assemblage type data, and can thus be of utility for analyzing
      sequential archaeological data from the same area or other similarly organized
      material.

PMID- 25970581
TI  - Game intelligence in team sports.
AB  - We set up a game theoretic framework to analyze a wide range of situations from
      team sports. A fundamental idea is the concept of potential; the probability of
      the offense scoring the next goal minus the probability that the next goal is
      made by the defense. We develop categorical as well as continuous models, and
      obtain optimal strategies for both offense and defense. A main result is that the
      optimal defensive strategy is to minimize the maximum potential of all offensive
      strategies. 

PMID- 25970579
TI  - Multilocus heterozygosity and coronary heart disease: nested case-control studies
      in men and women.
AB  - BACKGROUND: Generalized allelic heterozygosity has been proposed to improve
      reproductive fitness and has been associated with higher blood pressure, but its
      association with chronic disease is not well characterized. METHODS: Using the
      Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in
      parallel case-control studies of coronary heart disease (CHD) nested in the
      Health Professionals Follow-up Study and Nurses' Health Study. We examined
      ~700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and
      878 matched controls and 435 women with incident CHD with 931 matched controls.
      We examined the relationship of genome-wide heterozygosity with risk of incident
      of CHD and with baseline levels of cardiovascular risk factors. RESULTS: In both
      cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of
      heterozygous SNPs was not related to risk of CHD in either men or women (adjusted
      odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13]
      in women and 0.94 [0.84-1.06] in men). We also found no consistent associations
      of genome-wide heterozygosity with levels of lipids, inflammatory markers,
      adhesion molecules, homocysteine, adiponectin, or body-mass index. CONCLUSIONS:
      In these parallel nested case-control studies, we found no relationship of
      multilocus heterozygosity with risk of CHD or its major risk factors. Studies in
      other populations are needed to rule out associations with lower levels of
      heterozygosity.

PMID- 25970580
TI  - The Daily Movement Pattern and Fulfilment of Physical Activity Recommendations in
      Swedish Middle-Aged Adults: The SCAPIS Pilot Study.
AB  - Different aspects of the daily movement pattern--sitting, light intensity
      physical activity, and moderate- and vigorous intensity physical activity--have
      each independently been associated with health and longevity. Previous knowledge
      of the amount and distribution of these aspects in the general Swedish
      population, as well as the fulfilment rate of physical activity recommendations,
      mainly relies on self-reported data. More detailed data assessed with objective
      methods is needed. The aim of the study was to present descriptive data on the
      daily movement pattern in a middle-aged Swedish population assessed by hip-worn
      accelerometers. The cohort consisted of 948 participants (51% women), aged 50 to
      64 years, from the Swedish CArdioPulmonary bioImage pilot Study. In the total
      sample, 60.5% of accelerometer wear time was spent sitting, 35.2% in light
      physical activity and 3.9% in moderate- and vigorous physical activity. Men and
      participants with high educational level spent a larger proportion of time
      sitting, compared to women and participants with low educational level. Men and
      participants with a high educational level spent more time, and the oldest age
      group spent less time, in moderate- and vigorous physical activity. Only 7.1% of
      the study population met the current national physical activity recommendations,
      with no gender, age or education level differences. Assessment of all three
      components of the daily movement pattern is of high clinical relevance and should
      be included in future research. As the fulfilment of national physical activity
      recommendations is very low and sitting time is very high in our middle-aged
      population, the great challenge remains to enhance the implementation of methods
      to increase the level of physical activity in this population.

PMID- 25970582
TI  - The effects of plastic film mulching on maize growth and water use in dry and
      rainy years in Northeast China.
AB  - Plastic film mulching (PM) has been widely used to improve maize (Zea mays L.)
      yields and water use efficiency (WUE) in Northeast China, but the effects of PM
      in a changing climate characterized by highly variable precipitation are not well
      understood. Six site-year field experiments were conducted in the dry and rainy
      years to investigate the effects of PM on maize growth, grain yield, and WUE in
      Northeast China. Compared to crops grown without PM treatment (control, CK), PM
      significantly increased the grain yield by 15-26% in the dry years, but no
      significant yield increase was observed in the rainy years. Yield increase in the
      dry years was mainly due to a large increase in dry matter accumulation pre
      silking compared to the CK, which resulted from a greater dry matter accumulation
      rate due to the higher topsoil temperature and water content. As a result, the
      WUE of the crops that underwent PM (3.27 kg m(-3)) treatment was also increased
      by around 16% compared to the CK, although the overall evapotranspiration was
      similar between the two treatments. In the rainy years, due to frequent
      precipitation and scant sunshine, the topsoil temperature and water content in
      the field that received PM treatment was improved only at some stages and failed
      to cause higher dry matter accumulation, except at the 8th leaf stage.
      Consequently, the grain yield and WUE were not improved by PM in the rainy years.
      In addition, we found that PM caused leaf senescence at the late growth stage in
      both dry and rainy years. Therefore, in practice, PM should be applied
      cautiously, especially when in-season precipitation is taken into account.

PMID- 25970583
TI  - Prey Capture Ecology of the Cubozoan Carukia barnesi.
AB  - Adult Carukia barnesi medusae feed predominantly on larval fish; however, their
      mode of prey capture seems more complex than previously described. Our findings
      revealed that during light conditions, this species extends its tentacles and
      'twitches' them frequently. This highlights the lure-like nematocyst clusters in
      the water column, which actively attract larval fish that are consequently stung
      and consumed. This fishing behavior was not observed during dark conditions,
      presumably to reduce energy expenditure when they are not luring visually
      oriented prey. We found that larger medusae have longer tentacles; however, the
      spacing between the nematocyst clusters is not dependent on size, suggesting that
      the spacing of the nematocyst clusters is important for prey capture.
      Additionally, larger specimens twitch their tentacles more frequently than small
      specimens, which correlate with their recent ontogenetic prey shift from plankton
      to larval fish. These results indicate that adult medusae of C. barnesi are not
      opportunistically grazing in the water column, but instead utilize sophisticated
      prey capture techniques to specifically target larval fish. 

PMID- 25970584
TI  - Differential Phosphorylation of RNA Polymerase III and the Initiation Factor
      TFIIIB in Saccharomyces cerevisiae.
AB  - The production of ribosomes and tRNAs for protein synthesis has a high energetic
      cost and is under tight transcriptional control to ensure that the level of RNA
      synthesis is balanced with nutrient availability and the prevailing environmental
      conditions. In the RNA polymerase (pol) III system in yeast, nutrients and stress
      affect transcription through a bifurcated signaling pathway in which protein
      kinase A (PKA) and TORC1 activity directly or indirectly, through downstream
      kinases, alter the phosphorylation state and function of the Maf1 repressor and
      Rpc53, a TFIIF-like subunit of the polymerase. However, numerous lines of
      evidence suggest greater complexity in the regulatory network including the
      phosphoregulation of other pol III components. To address this issue, we
      systematically examined all 17 subunits of pol III along with the three subunits
      of the initiation factor TFIIIB for evidence of differential phosphorylation in
      response to inhibition of TORC1. A relatively high stoichiometry of
      phosphorylation was observed for several of these proteins and the Rpc82 subunit
      of the polymerase and the Bdp1 subunit of TFIIIB were found to be differentially
      phosphorylated. Bdp1 is phosphorylated on four major sites during exponential
      growth and the protein is variably dephosphorylated under conditions that inhibit
      tRNA gene transcription. PKA, the TORC1-regulated kinase Sch9 and protein kinase
      CK2 are all implicated in the phosphorylation of Bdp1. Alanine substitutions at
      the four phosphosites cause hyper-repression of transcription indicating that
      phosphorylation of Bdp1 opposes Maf1-mediated repression. The new findings
      suggest an integrated regulatory model for signaling events controlling pol III
      transcription. 

PMID- 25970585
TI  - Differences in Attack Avoidance and Mating Success between Strains Artificially
      Selected for Dispersal Distance in Tribolium castaneum.
AB  - Individuals of both dispersal and non-dispersal types (disperser and non
      disperser) are found in a population, suggesting that each type has both costs
      and benefits for fitness. However, few studies have examined the trade-off
      between the costs and benefits for the types. Here, we artificially selected for
      walking distance, i.e., an indicator of dispersal ability, in the red flour
      beetle Tribolium castaneum and established strains with longer (L-strains) or
      shorter (S-strains) walking distances. We then compared the frequency of
      predation by the assassin bug Amphibolus venator and the mating frequency of the
      selected strains. L-strain beetles suffered higher predation risk, than did S
      strain beetles. L-strain males had significantly increased mating success
      compared to S-strain males, but females did not show a significant difference
      between the strains. The current results showed the existence of a trade-off
      between predation avoidance and mating success associated with dispersal types at
      a genetic level only in males. This finding can help to explain the maintenance
      of variation in dispersal ability within a population. 

PMID- 25970587
TI  - Structural biology of bacterial RNA polymerase.
AB  - Since its discovery and characterization in the early 1960s (Hurwitz, J. The
      discovery of RNA polymerase. J. Biol. Chem. 2005, 280, 42477-42485), an enormous
      amount of biochemical, biophysical and genetic data has been collected on
      bacterial RNA polymerase (RNAP). In the late 1990s, structural information
      pertaining to bacterial RNAP has emerged that provided unprecedented insights
      into the function and mechanism of RNA transcription. In this review, I list all
      structures related to bacterial RNAP (as determined by X-ray crystallography and
      NMR methods available from the Protein Data Bank), describe their contributions
      to bacterial transcription research and discuss the role that small molecules
      play in inhibiting bacterial RNA transcription. 

PMID- 25970588
TI  - Reef fishes in biodiversity hotspots are at greatest risk from loss of coral
      species.
AB  - Coral reef ecosystems are under a variety of threats from global change and
      anthropogenic disturbances that are reducing the number and type of coral species
      on reefs. Coral reefs support upwards of one third of all marine species of fish,
      so the loss of coral habitat may have substantial consequences to local fish
      diversity. We posit that the effects of habitat degradation will be most severe
      in coral regions with highest biodiversity of fishes due to greater
      specialization by fishes for particular coral habitats. Our novel approach to
      this important but untested hypothesis was to conduct the same field experiment
      at three geographic locations across the Indo-Pacific biodiversity gradient
      (Papua New Guinea; Great Barrier Reef, Australia; French Polynesia).
      Specifically, we experimentally explored whether the response of local fish
      communities to identical changes in diversity of habitat-providing corals was
      independent of the size of the regional species pool of fishes. We found that the
      proportional reduction (sensitivity) in fish biodiversity to loss of coral
      diversity was greater for regions with larger background species pools,
      reflecting variation in the degree of habitat specialization of fishes across the
      Indo-Pacific diversity gradient. This result implies that habitat-associated fish
      in diversity hotspots are at greater risk of local extinction to a given loss of
      habitat diversity compared to regions with lower species richness. This
      mechanism, related to the positive relationship between habitat specialization
      and regional biodiversity, and the elevated extinction risk this poses for
      biodiversity hotspots, may apply to species in other types of ecosystems. 

PMID- 25970589
TI  - Noninvasive Digital Detection of Fetal DNA in Plasma of 4-Week-Pregnant Women
      following In Vitro Fertilization and Embryo Transfer.
AB  - The discovery of cell-free fetal DNA (cfDNA) circulating in the maternal blood
      has provided new opportunities for noninvasive prenatal diagnosis (NIPD).
      However, the extremely low levels of cfDNA within a high background of the
      maternal DNA in maternal circulation necessitate highly sensitive molecular
      techniques for its reliable use in NIPD. In this proof of principle study, we
      evaluated the earliest possible detection of cfDNA in the maternal plasma by a
      bead-based emulsion PCR technology known as BEAMing (beads, emulsion,
      amplification, magnetics). Blood samples were collected from in vitro
      fertilization (IVF) patients at 2 to 6 weeks following embryo transfer (i.e., 4
      to 8 week pregnancies) and plasma DNA was extracted. The genomic regions of both
      X and Y chromosome-specific sequences (AMELX and AMELY) were concurrently
      amplified in two sequential PCRs; first by conventional PCR then by BEAMing. The
      positive beads either for AMELX or AMELY gene sequences were counted by a flow
      cytometer. Our results showed that the pregnancies yielding boys had
      significantly higher plasma AMELY gene fractions (0.512 +/- 0.221) than the ones
      yielding girls (0.028 +/- 0.003) or non-pregnant women (0.020 +/- 0.005, P=
      0.0059). Here, we clearly demonstrated that the BEAMing technique is capable of
      reliably detecting cfDNA in the blood circulation of 4-week-pregnant women, which
      is only two weeks after the embryo transfer. BEAMing technique can also be used
      to early detect fetal DNA alterations in other pregnancy-associated disorders. 

PMID- 25970590
TI  - Evaluation of the Capacity of PCR and High-Resolution Melt Curve Analysis for
      Identification of Mixed Infection with Mycoplasma gallisepticum Strains.
AB  - Pathogenicity and presentation of Mycoplasma gallisepticum (MG) infection may
      differ from one strain to another and this may have implications on control
      measures. Infection of individual birds with more than one MG strain has been
      reported. A PCR followed by high resolution melt (HRM) curve analysis has been
      developed in our laboratory and routinely used for detection and differentiation
      of MG strains. However the potential of this test for identification of MG
      strains in a mixed specimen has not been evaluated. In the present study, the
      capability of PCR-HRM curve analysis technique, targeting vlhA and pvpA genes was
      assessed for identification of individual MG strains in a mixed population.
      Different DNA ratios of two MG strains from 1 to 10(-4) ng were tested with some
      generated conventional and normalized curves distinct from those of individual
      strains alone. Using genotype confidence percentages (GCP) generated from HRM
      curve analysis, it was found that vlhA PCR-HRM was more consistent than pvpA PCR
      HRM for the detection of MG ts-11 vaccine strain mixed with any of the MG strains
      6/85, F, S6 or a field isolate. The potential of vlhA PCR-HRM to detect mixed MG
      strains in a specimen was found to be primarily dependent on quantity and
      proportion of the target DNAs in the mixture. This is the first study examining
      the capacity of PCR-HRM technique for identification of individual MG strains in
      a mixed strain population.

PMID- 25970592
TI  - Sample preconcentration utilizing nanofractures generated by junction gap
      breakdown assisted by self-assembled monolayer of gold nanoparticles.
AB  - The preconcentration of proteins with low concentrations can be used to increase
      the sensitivity and accuracy of detection. A nonlinear electrokinetic flow is
      induced in a nanofluidic channel due to the overlap of electrical double layers,
      resulting in the fast accumulation of proteins, referred to as the exclusion
      enrichment effect. The proposed chip for protein preconcentration was fabricated
      using simple standard soft lithography with a polydimethylsiloxane replica. This
      study extends our previous paper, in which gold nanoparticles were manually
      deposited onto the surface of a protein preconcentrator. In the present work,
      nanofractures were formed by utilizing the self-assembly of gold-nanoparticle
      assisted electric breakdown. This reliable method for nanofracture formation,
      involving self-assembled monolayers of nanoparticles at the junction gap between
      microchannels, also decreases the required electric breakdown voltage. The
      experimental results reveal that a high concentration factor of 1.5*10(4) for a
      protein sample with an extremely low concentration of 1 nM was achieved in 30 min
      by using the proposed chip, which is faster than our previously proposed chip at
      the same conditions. Moreover, an immunoassay of bovine serum albumin (BSA) and
      anti-BSA was carried out to demonstrate the applicability of the proposed chip.

PMID- 25970586
TI  - Oxidative stress and the homeodynamics of iron metabolism.
AB  - Iron and oxygen share a delicate partnership since both are indispensable for
      survival, but if the partnership becomes inadequate, this may rapidly terminate
      life. Virtually all cell components are directly or indirectly affected by
      cellular iron metabolism, which represents a complex, redox-based machinery that
      is controlled by, and essential to, metabolic requirements. Under conditions of
      increased oxidative stress-i.e., enhanced formation of reactive oxygen species
      (ROS)-however, this machinery may turn into a potential threat, the continued
      requirement for iron promoting adverse reactions such as the iron/H2O2-based
      formation of hydroxyl radicals, which exacerbate the initial pro-oxidant
      condition. This review will discuss the multifaceted homeodynamics of cellular
      iron management under normal conditions as well as in the context of oxidative
      stress.

PMID- 25970591
TI  - In Vivo Monitoring of Dopamine by Microdialysis with 1 min Temporal Resolution
      Using Online Capillary Liquid Chromatography with Electrochemical Detection.
AB  - Microdialysis is often applied to understanding brain function. Because
      neurotransmission involves rapid events, increasing the temporal resolution of in
      vivo measurements is desirable. Here, we demonstrate microdialysis with online
      capillary liquid chromatography for the analysis of 1 min rat brain dialysate
      samples at 1 min intervals. Mobile phase optimization involved adjusting the pH,
      buffer composition, and surfactant concentration to eliminate interferences with
      the dopamine peak. By analyzing electrically evoked dopamine transients carefully
      synchronized with the switching of the online LC sample valve, we demonstrate
      that our system has both 1 min sampling capabilities and bona fide 1 min temporal
      resolution. Evoked DA transients were confined to single, 1 min brain dialysate
      samples. After uptake inhibition with nomifensine (20 mg/kg i.p.), responses to
      electrical stimuli of 1 s duration were detected. 

PMID- 25970593
TI  - Coverage of the expanded program on immunization in Vietnam: Results from 2
      cluster surveys and routine reports.
AB  - The Expanded Program on Immunization (EPI) in Vietnam began in 1981 and reached a
      87% national coverage rate in 1987. To investigate the vaccination coverage and
      trends in time of the EPI in Vietnam, 2 vaccine coverage cluster surveys have
      been conducted in 2003 and 2009. Information on EPI-vaccine coverage in children
      (aged 0-23 months - 7 y of age), in women of childbearing age and in pregnant
      women, was collected through '30 cluster surveys' in 2003 and 2009 (according to
      the World Health Organization (WHO) methodology) and through routine annual EPI
      coverage reports for the period 2001-2008. By comparing both cluster survey
      studies with each other, as well as with routinely collected data, we aim to
      improve future evaluation of the vaccination coverage in Vietnam and deduce
      recommendations for the immunization program. According to both methods, the
      national targets were reached for most of the vaccines: over 90% of children are
      fully immunized by 1 y of age, 80% Tetanus Toxoid 2 Plus (TT2+) coverage is
      reached for pregnant women, and 90% TT2+ for childbearing aged women. The cluster
      surveys identified higher coverage rates compared to the routinely reported data
      in some provinces regarding the percentage of fully immunized children by the age
      of 1 year, and confirmed a low coverage rate for hepatitis B birth dose
      vaccination in all surveyed sites. CONCLUSION: Both methods of coverage
      assessment suggest that national targets are reached, for most but not all
      vaccines and not in all regions. Managing stock pile issues, addressing safety
      issues and tailoring policy for remote areas, are important elements to maintain
      and further improve these coverage figures.

PMID- 25970594
TI  - Impact of a moving noise masker on speech perception in cochlear implant users.
AB  - OBJECTIVES: Previous studies investigating speech perception in noise have
      typically been conducted with static masker positions. The aim of this study was
      to investigate the effect of spatial separation of source and masker (spatial
      release from masking, SRM) in a moving masker setup and to evaluate the impact of
      adaptive beamforming in comparison with fixed directional microphones in cochlear
      implant (CI) users. DESIGN: Speech reception thresholds (SRT) were measured in
      S0N0 and in a moving masker setup (S0Nmove) in 12 normal hearing participants and
      14 CI users (7 subjects bilateral, 7 bimodal with a hearing aid in the
      contralateral ear). Speech processor settings were a moderately directional
      microphone, a fixed beamformer, or an adaptive beamformer. The moving noise
      source was generated by means of wave field synthesis and was smoothly moved in a
      shape of a half-circle from one ear to the contralateral ear. Noise was presented
      in either of two conditions: continuous or modulated. RESULTS: SRTs in the
      S0Nmove setup were significantly improved compared to the S0N0 setup for both the
      normal hearing control group and the bilateral group in continuous noise, and for
      the control group in modulated noise. There was no effect of subject group. A
      significant effect of directional sensitivity was found in the S0Nmove setup. In
      the bilateral group, the adaptive beamformer achieved lower SRTs than the fixed
      beamformer setting. Adaptive beamforming improved SRT in both CI user groups
      substantially by about 3 dB (bimodal group) and 8 dB (bilateral group) depending
      on masker type. CONCLUSIONS: CI users showed SRM that was comparable to normal
      hearing subjects. In listening situations of everyday life with spatial
      separation of source and masker, directional microphones significantly improved
      speech perception with individual improvements of up to 15 dB SNR. Users of
      bilateral speech processors with both directional microphones obtained the
      highest benefit.

PMID- 25970595
TI  - Patterns of gut bacterial colonization in three primate species.
AB  - Host fitness is impacted by trillions of bacteria in the gastrointestinal tract
      that facilitate development and are inextricably tied to life history. During
      development, microbial colonization primes the gut metabolism and physiology,
      thereby setting the stage for adult nutrition and health. However, the ecological
      rules governing microbial succession are poorly understood. In this study, we
      examined the relationship between host lineage, captive diet, and life stage and
      gut microbiota characteristics in three primate species (infraorder,
      Lemuriformes). Fecal samples were collected from captive lemur mothers and their
      infants, from birth to weaning. Microbial DNA was extracted and the v4 region of
      16S rDNA was sequenced on the Illumina platform using protocols from the Earth
      Microbiome Project. Here, we show that colonization proceeds along different
      successional trajectories in developing infants from species with differing
      dietary regimes and ecological profiles: frugivorous (fruit-eating) Varecia
      variegata, generalist Lemur catta, and folivorous (leaf-eating) Propithecus
      coquereli. Our analyses reveal community membership and succession patterns
      consistent with previous studies of human infants, suggesting that lemurs may
      serve as a useful model of microbial ecology in the primate gut. Each lemur
      species exhibits distinct species-specific bacterial diversity signatures
      correlating to life stages and life history traits, implying that gut microbial
      community assembly primes developing infants at species-specific rates for their
      respective adult feeding strategies. 

PMID- 25970597
TI  - WITHDRAWN: Haemostatic drugs for traumatic brain injury.

PMID- 25970596
TI  - Altered activation of innate immunity associates with white matter volume and
      diffusion in first-episode psychosis.
AB  - First-episode psychosis (FEP) is associated with inflammatory and brain
      structural changes, but few studies have investigated whether systemic
      inflammation associates with brain structural changes in FEP. Thirty-seven FEP
      patients (median 27 days on antipsychotic medication), and 19 matched controls
      were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular
      risk markers were measured at baseline and 2 months later. We collected T1- and
      diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We
      analyzed the association of psychosis-related inflammatory markers with gray and
      white matter (WM) volume using voxel-based morphometry and WM diffusion using
      tract-based spatial statistics with whole-brain and region-of-interest (ROI)
      analyses. FEP patients had higher CCL22 and lower TGFalpha, CXCL1, CCL7, IFN
      alpha2 and ApoA-I than controls. CCL22 decreased significantly between baseline
      and 2 months in patients but was still higher than in controls. The association
      between inflammatory markers and FEP remained significant after adjusting for
      age, sex, smoking and BMI. We did not observe a correlation of inflammatory
      markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22
      levels correlated negatively with WM volume and positively with mean diffusivity
      and radial diffusivity bilaterally in the frontal lobes in ROI analyses.
      Decreased serum level of ApoA-I was associated with smaller volume of the medial
      temporal WM. In whole-brain analyses, CCL22 correlated positively with mean
      diffusivity and radial diffusivity, and CXCL1 associated negatively with
      fractional anisotropy and positively with mean diffusivity and radial diffusivity
      in several brain regions. This is the first report to demonstrate an association
      between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22
      has been previously implicated in autoimmune diseases associated with WM
      pathology. The results suggest that an altered activation of innate immunity may
      contribute to WM damage in psychotic disorders. 

PMID- 25970598
TI  - [Acute Carpal Tunnel Syndrome due to Spontaneous Bleeding after Taking
      Rivaroxaban (Xarelto(r))].
AB  - A 64-year-old man suffered from acute carpal tunnel syndrome of his right hand
      without explainable reason. An emergency operation drained a pronounced
      haematoma. There is a strong suspicion this was a bleeding complication related
      to taking rivaroxaban (Xarelto((r))). 

PMID- 25970599
TI  - Deep Sequencing Analysis of the Ixodes ricinus Haemocytome.
AB  - BACKGROUND: Ixodes ricinus is the main tick vector of the microbes that cause
      Lyme disease and tick-borne encephalitis in Europe. Pathogens transmitted by
      ticks have to overcome innate immunity barriers present in tick tissues,
      including midgut, salivary glands epithelia and the hemocoel. Molecularly,
      invertebrate immunity is initiated when pathogen recognition molecules trigger
      serum or cellular signalling cascades leading to the production of
      antimicrobials, pathogen opsonization and phagocytosis. We presently aimed at
      identifying hemocyte transcripts from semi-engorged female I. ricinus ticks by
      mass sequencing a hemocyte cDNA library and annotating immune-related transcripts
      based on their hemocyte abundance as well as their ubiquitous distribution.
      METHODOLOGY/PRINCIPAL FINDINGS: De novo assembly of 926,596 pyrosequence reads
      plus 49,328,982 Illumina reads (148 nt length) from a hemocyte library, together
      with over 189 million Illumina reads from salivary gland and midgut libraries,
      generated 15,716 extracted coding sequences (CDS); these are displayed in an
      annotated hyperlinked spreadsheet format. Read mapping allowed the identification
      and annotation of tissue-enriched transcripts. A total of 327 transcripts were
      found significantly over expressed in the hemocyte libraries, including those
      coding for scavenger receptors, antimicrobial peptides, pathogen recognition
      proteins, proteases and protease inhibitors. Vitellogenin and lipid metabolism
      transcription enrichment suggests fat body components. We additionally annotated
      ubiquitously distributed transcripts associated with immune function, including
      immune-associated signal transduction proteins and transcription factors,
      including the STAT transcription factor. CONCLUSIONS/SIGNIFICANCE: This is the
      first systems biology approach to describe the genes expressed in the haemocytes
      of this neglected disease vector. A total of 2,860 coding sequences were
      deposited to GenBank, increasing to 27,547 the number so far deposited by our
      previous transcriptome studies that serves as a discovery platform for studies
      with I. ricinus biochemistry and physiology.

PMID- 25970600
TI  - Exploring potential of pearl millet germplasm association panel for association
      mapping of drought tolerance traits.
AB  - A pearl millet inbred germplasm association panel (PMiGAP) comprising 250 inbred
      lines, representative of cultivated germplasm from Africa and Asia, elite
      improved open-pollinated cultivars, hybrid parental inbreds and inbred mapping
      population parents, was recently established. This study presents the first
      report of genetic diversity in PMiGAP and its exploitation for association
      mapping of drought tolerance traits. For diversity and genetic structure
      analysis, PMiGAP was genotyped with 37 SSR and CISP markers representing all
      seven linkage groups. For association analysis, it was phenotyped for yield and
      yield components and morpho-physiological traits under both well-watered and
      drought conditions, and genotyped with SNPs and InDels from seventeen genes
      underlying a major validated drought tolerance (DT) QTL. The average gene
      diversity in PMiGAP was 0.54. The STRUCTURE analysis revealed six subpopulations
      within PMiGAP. Significant associations were obtained for 22 SNPs and 3 InDels
      from 13 genes under different treatments. Seven SNPs associations from 5 genes
      were common under irrigated and one of the drought stress treatments. Most
      significantly, an important SNP in putative acetyl CoA carboxylase gene showed
      constitutive association with grain yield, grain harvest index and panicle yield
      under all treatments. An InDel in putative chlorophyll a/b binding protein gene
      was significantly associated with both stay-green and grain yield traits under
      drought stress. This can be used as a functional marker for selecting high
      yielding genotypes with 'stay green' phenotype under drought stress. The present
      study identified useful marker-trait associations of important agronomics traits
      under irrigated and drought stress conditions with genes underlying a major
      validated DT-QTL in pearl millet. Results suggest that PMiGAP is a useful panel
      for association mapping. Expression patterns of genes also shed light on some
      physiological mechanisms underlying pearl millet drought tolerance. 

PMID- 25970601
TI  - PAPST, a User Friendly and Powerful Java Platform for ChIP-Seq Peak Co
      Localization Analysis and Beyond.
AB  - Comparative co-localization analysis of transcription factors (TFs) and
      epigenetic marks (EMs) in specific biological contexts is one of the most
      critical areas of ChIP-Seq data analysis beyond peak calling. Yet there is a
      significant lack of user-friendly and powerful tools geared towards co
      localization analysis based exploratory research. Most tools currently used for
      co-localization analysis are command line only and require extensive installation
      procedures and Linux expertise. Online tools partially address the usability
      issues of command line tools, but slow response times and few customization
      features make them unsuitable for rapid data-driven interactive exploratory
      research. We have developed PAPST: Peak Assignment and Profile Search Tool, a
      user-friendly yet powerful platform with a unique design, which integrates both
      gene-centric and peak-centric co-localization analysis into a single package.
      Most of PAPST's functions can be completed in less than five seconds, allowing
      quick cycles of data-driven hypothesis generation and testing. With PAPST, a
      researcher with or without computational expertise can perform sophisticated co
      localization pattern analysis of multiple TFs and EMs, either against all known
      genes or a set of genomic regions obtained from public repositories or prior
      analysis. PAPST is a versatile, efficient, and customizable tool for genome-wide
      data-driven exploratory research. Creatively used, PAPST can be quickly applied
      to any genomic data analysis that involves a comparison of two or more sets of
      genomic coordinate intervals, making it a powerful tool for a wide range of
      exploratory genomic research. We first present PAPST's general purpose features
      then apply it to several public ChIP-Seq data sets to demonstrate its rapid
      execution and potential for cutting-edge research with a case study in enhancer
      analysis. To our knowledge, PAPST is the first software of its kind to provide
      efficient and sophisticated post peak-calling ChIP-Seq data analysis as an easy
      to-use interactive application. PAPST is available at
      https://github.com/paulbible/papst and is a public domain work. 

PMID- 25970604
TI  - IFN-lambda gene polymorphisms as predictive factors in chronic hepatitis C
      treatment-naive patients without access to protease inhibitors.
AB  - The single nucleotides polymorphisms analyses in the regions near the IL28B gene
      in patients chronically infected with genotype 1 hepatitis C virus (HCV) are an
      important predictive factor for sustained virological response (SVR). The aim was
      to assess the predictive value of the polymorphisms of the IL28B/IFNL3 gene in
      patients chronically infected with genotype 1 for the viral clearance obtained
      after initial treatment including admixed populations. A systematic review was
      conducted, using a meta-analysis in the PubMed, Embase, LILACS, and SCIELO using
      MesH and DECS in 42 studies. The parameters were IL28B polymorphisms, rs12979860,
      rs8099917, and rs12980275, SVR ratio, and OR (odds ratio). OR and confidence
      Interval of 95% (95%CI), were calculated by fixed or random effects models.
      Heterogeneity, sensitivity analysis, and publication bias were also performed.
      Significant differences were noted between carriers groups with the major versus
      minor allele at rs12979860 CC versus CT/TT-genotype (OR = 4.18; 95%CI = 3.37
      5.17), rs8099917 TT versus TG/GG-genotype (OR = 4.07; 95%CI = 2.94-5.63), and
      rs12980275 AA versus AA/AG-genotype (OR = 5.34; 95%CI = 1.60-17.82). There was
      selection bias in the rs8099917 analysis (Egger's regression P = 0.049), which
      reversed after performing a sensitivity analysis (P = 0.510). The incorporation
      of SNP analyses in IL28B/IFNL3 gene during the diagnosis process in Brazil should
      be used as a complementary tool to determine the appropriate treatment for HCV
      genotype 1. Here, we confirm that the rs12979860 CC, rs8099917 TT, and rs12980275
      AA genotype-carriers have favorable responses to standard therapy, including two
      studies with Brazilian population, and this information should be considered.

PMID- 25970602
TI  - Osteological, biomolecular and geochemical examination of an early anglo-saxon
      case of lepromatous leprosy.
AB  - We have examined a 5th to 6th century inhumation from Great Chesterford, Essex,
      UK. The incomplete remains are those of a young male, aged around 21-35 years at
      death. The remains show osteological evidence of lepromatous leprosy (LL) and
      this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis,
      which provided evidence for both multi-copy and single copy loci from the
      Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I
      lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains
      found in later medieval cases in southern Britain and also continental Europe.
      While a number of contemporaneous cases exist, at present, this case of leprosy
      is the earliest radiocarbon dated case in Britain confirmed by both aDNA and
      lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that
      the individual is likely to have originated from outside Britain. This
      potentially sheds light on the origins of the strain in Britain and its
      subsequent spread to other parts of the world, including the Americas where the
      3I lineage of M. leprae is still found in some southern states of America. 

PMID- 25970605
TI  - Tissue-like Silicon Nanowires-Based Three-Dimensional Anodes for High-Capacity
      Lithium Ion Batteries.
AB  - Here, we report on the scalable synthesis and characterization of novel
      architecture three-dimensional (3D) high-capacity amorphous silicon nanowires
      (SiNWs)-based anodes with focus on studying their electrochemical degradation
      mechanisms. We achieved an unprecedented combination of remarkable performance
      characteristics, high loadings of 3-15 mAh/cm(2), a very low irreversible
      capacity (10% for the 3-4 mAh/cm(2) anodes), current efficiency greater than
      99.5%, cycle stability (both in half cells and a LiFePO4 battery), a total
      capacity of 457 mAh/cm(2) over 204 cycles and fast charge-discharge rates (up to
      2.7C at 20 mA/cm(2)). These SiNWs-based binder-free 3D anodes have been cycled
      for over 200 cycles, exhibiting a stable cycle life. Notably, it was found that
      the growth of the continuous SEI layer thickness, and its concomitant increase in
      resistivity, represents the major reason for the observed capacity loss of the
      SiNWs-based anodes. Importantly, these NWs-based anodes of novel architecture
      meet the requirements of lithium batteries for future portable, and electric
      vehicle, applications. 

PMID- 25970603
TI  - Mechanisms of Nifedipine-Downregulated CD40L/sCD40L Signaling in Collagen
      Stimulated Human Platelets.
AB  - The platelet-derived soluble CD40L (sCD40L) release plays a critical role in the
      development of atherosclerosis. Nifedipine, a dihydropyridine-based L-type
      calcium channel blocker (CCB), has been reported to have an anti-atherosclerotic
      effect beyond its blood pressure-lowering effect, but the molecular mechanisms
      remain unclear. The present study was designed to investigate whether nifedipine
      affects sCD40L release from collagen-stimulated human platelets and to determine
      the potential role of peroxisome proliferator-activated receptor-beta/-gamma
      (PPAR-beta/-gamma). We found that treatment with nifedipine significantly
      inhibited the platelet surface CD40L expression and sCD40L release in response to
      collagen, while the inhibition was markedly reversed by blocking PPAR-beta/-gamma
      activity with specific antagonist such as GSK0660 and GW9662. Meanwhile,
      nifedipine also enhanced nitric oxide (NO) and cyclic GMP formation in a PPAR
      beta/-gamma-dependent manner. When the NO/cyclic GMP pathway was suppressed,
      nifedipine-mediated inhibition of sCD40L release was abolished significantly.
      Collagen-induced phosphorylation of p38MAPK, ERK1/2 and HSP27, matrix
      metalloproteinase-2 (MMP-2) expression/activity and reactive oxygen species (ROS)
      formation were significantly inhibited by nifedipine, whereas these alterations
      were all attenuated by co-treatment with PPAR-beta/-gamma antagonists.
      Collectively, these results demonstrate that PPAR-beta/-gamma-dependent pathways
      contribute to nifedipine-mediated downregulation of CD40L/sCD40L signaling in
      activated platelets through regulation of NO/ p38MAPK/ERK1/2/HSP27/MMP-2
      signalings and provide a novel mechanism regarding the anti-atherosclerotic
      effect of nifedipine. 

PMID- 25970606
TI  - Microbial community in high arsenic shallow groundwater aquifers in Hetao Basin
      of Inner Mongolia, China.
AB  - A survey was carried out on the microbial community of 20 groundwater samples (4
      low and 16 high arsenic groundwater) and 19 sediments from three boreholes (two
      high arsenic and one low arsenic boreholes) in a high arsenic groundwater system
      located in Hetao Basin, Inner Mongolia, using the 454 pyrosequencing approach. A
      total of 233,704 sequence reads were obtained and classified into 12-267
      operational taxonomic units (OTUs). Groundwater and sediment samples were divided
      into low and high arsenic groups based on measured geochemical parameters and
      microbial communities, by hierarchical clustering and principal coordinates
      analysis. Richness and diversity of the microbial communities in high arsenic
      sediments are higher than those in high arsenic groundwater. Microbial community
      structure was significantly different either between low and high arsenic samples
      or between groundwater and sediments. Acinetobacter, Pseudomonas, Psychrobacter
      and Alishewanella were the top four genera in high arsenic groundwater, while
      Thiobacillus, Pseudomonas, Hydrogenophaga, Enterobacteriaceae, Sulfuricurvum and
      Arthrobacter dominated high arsenic sediments. Archaeal sequences in high arsenic
      groundwater were mostly related to methanogens. Biota-environment matching and co
      inertia analyses showed that arsenic, total organic carbon, SO4(2-), SO4(2
      )/total sulfur ratio, and Fe(2+) were important environmental factors shaping the
      observed microbial communities. The results of this study expand our current
      understanding of microbial ecology in high arsenic groundwater aquifers and
      emphasize the potential importance of microbes in arsenic transformation in the
      Hetao Basin, Inner Mongolia.

PMID- 25970607
TI  - Unexpected dual task benefits on cycling in Parkinson disease and healthy adults:
      a neuro-behavioral model.
AB  - BACKGROUND: When performing two tasks at once, a dual task, performance on one or
      both tasks typically suffers. People with Parkinson's disease (PD) usually
      experience larger dual task decrements on motor tasks than healthy older adults
      (HOA). Our objective was to investigate the decrements in cycling caused by
      performing cognitive tasks with a range of difficulty in people with PD and HOAs.
      METHODS: Twenty-eight participants with Parkinson's disease and 20 healthy older
      adults completed a baseline cycling task with no secondary tasks and then
      completed dual task cycling while performing 12 tasks from six cognitive domains
      representing a wide range of difficulty. RESULTS: Cycling was faster during dual
      task conditions than at baseline, and was significantly faster for six tasks (all
      p<.02) across both groups. Cycling speed improved the most during the easiest
      cognitive tasks, and cognitive performance was largely unaffected. Cycling
      improvement was predicted by task difficulty (p<.001). People with Parkinson's
      disease cycled slower (p<.03) and showed reduced dual task benefits (p<.01) than
      healthy older adults. CONCLUSIONS: Unexpectedly, participants' motor performance
      improved during cognitive dual tasks, which cannot be explained in current models
      of dual task performance. To account for these findings, we propose a model
      integrating dual task and acute exercise approaches which posits that cognitive
      arousal during dual tasks increases resources to facilitate motor and cognitive
      performance, which is subsequently modulated by motor and cognitive task
      difficulty. This model can explain both the improvement observed on dual tasks in
      the current study and more typical dual task findings in other studies.

PMID- 25970608
TI  - Food-anticipatory activity in Syrian hamsters: behavioral and molecular responses
      in the hypothalamus according to photoperiodic conditions.
AB  - When food availability is restricted, animals adjust their behavior according to
      the timing of food access. Most rodents, such as rats and mice, and a wide number
      of other animals express before timed food access a bout of activity, defined as
      food-anticipatory activity (FAA). One notable exception amongst rodents is the
      Syrian hamster, a photoperiodic species that is not prone to express FAA. The
      present study was designed to understand the reasons for the low FAA in that
      species. First, we used both wheel-running activity and general cage activity to
      assess locomotor behavior. Second, the possible effects of photoperiod was tested
      by challenging hamsters with restricted feeding under long (LP) or short (SP)
      photoperiods. Third, because daytime light may inhibit voluntary activity,
      hamsters were also exposed to successive steps of full and skeleton photoperiods
      (two 1-h light pulses simulating dawn and dusk). When hamsters were exposed to
      skeleton photoperiods, not full photoperiod, they expressed FAA in the wheel
      independently of daylength, indicating that FAA in the wheel is masked by daytime
      light under full photoperiods. During FAA under skeleton photoperiods, c-Fos
      expression was increased in the arcuate nuclei independently of the photoperiod,
      but differentially increased in the ventromedial and dorsomedial hypothalamic
      nuclei according to the photoperiod. FAA in general activity was hardly modulated
      by daytime light, but was reduced under SP. Together, these findings show that
      food-restricted Syrian hamsters are not prone to display FAA under common
      laboratory conditions, because of the presence of light during daytime that
      suppresses FAA expression in the wheel. 

PMID- 25970609
TI  - Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and
      Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.
AB  - The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid
      receptor associated with bone remodelling, nervous system excitability, vascular
      homeostasis as well as in several pathophysiological conditions including obesity
      and cancer. However, its physiological role and underlying mechanism remain
      unclear. In the present work, we demonstrate for the first time its presence in
      human macrophages and its increased expression in ox-LDL-induced foam cells. In
      addition, pharmacological activation of GPR55 by its selective agonist O-1602
      increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol
      efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1,
      as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced
      proinflammatory responses in foam cells. Treatment with cannabidiol, a selective
      antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O
      1602-mediated effects. Our data suggest that GPR55 could play deleterious role in
      ox-LDL-induced foam cells and could be a novel pharmacological target to manage
      atherosclerosis and other related cardiovascular diseases. 

PMID- 25970610
TI  - Advances in umbilical cord blood stem cell expansion and clinical translation.
AB  - Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs)
      with important applications in allogeneic stem cell transplantation. However, the
      low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units
      remain a major limitation. Protocols developed for HSPC expansion ex vivo or to
      improve HSPC homing to the marrow represent solutions to overcome this
      shortcoming. In recent decades, wide arrays of functionally divergent approaches
      were developed for the amplification of HSPCs. These include optimization of
      cytokine cocktails, coculture systems, small molecules, and delivery systems for
      HSPC-expansion genes. Herein, we review past and current strategies, focusing on
      studies that characterize the contribution of expanded CB HSPC to short- and long
      term engraftment in transplantation models or in clinical trials. Also discussed
      are homing effectors used to promote engraftment. In summary, these studies
      underscore that early-acting cytokines alone can expand HSPC with short-term
      engraftment activity, but that robust expansion of HSPCs with long-term
      engraftment necessitates the synergistic action of multiple HSC-expansion
      agonists. In support of this, early clinical trials based on cytokine-driven HSPC
      expansion protocols delivered disappointing results, whereas recent trials based
      on the synergistic action of cytokines and HSPC-expansion agonists reported
      significant improvements in engraftment and therapeutic outcomes. Conversely,
      molecules that enhance homing of HSPC may represent a complementary approach to
      improve and perhaps accelerate engraftment. Optimization of the next generation
      of HSPC-expansion and priming strategies should support a paradigm shift in CB
      transplantation in which smaller, better matched units may preferentially be
      used.

PMID- 25970611
TI  - Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta
      Analysis.
AB  - BACKGROUND: Low doses of cadmium can cause adverse health effects. Benchmark dose
      (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points
      of departure for urinary cadmium exposure have been estimated in several previous
      studies, but the methods to derive BMD and the estimated BMDs differ. OBJECTIVES:
      We aimed to find the associated factors that affect BMD calculation in the
      general population, and to estimate the summary BMD for urinary cadmium using
      reported BMDs. METHODS: A meta-regression was performed and the pooled BMD/BMDL
      was estimated using studies reporting a BMD and BMDL, weighted by sample size,
      that were calculated from individual data based on markers of renal dysfunction.
      RESULTS: BMDs were highly heterogeneous across studies. Meta-regression analysis
      showed that a significant predictor of BMD was the cut-off point which denotes an
      abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for
      5% benchmark responses (BMR) of beta2-microglobulinuria (beta2-MG) estimated was
      6.18/4.88 MUg/g creatinine in conventional quantal analysis and 3.56/3.13 MUg/g
      creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N
      acetyl-beta-d-glucosaminidase (NAG) was 10.31/7.61 MUg/g creatinine in quantal
      analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta
      regression showed that BMD and BMDL were significantly associated with the cut
      off point, but BMD calculation method did not significantly affect the results.
      The urinary cadmium BMDL5 of beta2-MG was 1.9 MUg/g creatinine in the lowest cut
      off point group. CONCLUSION: The BMD was significantly associated with the cut
      off point defining the abnormal level of renal dysfunction markers.

PMID- 25970612
TI  - Geographic distribution of isolated indigenous societies in Amazonia and the
      efficacy of indigenous territories.
AB  - The headwaters of the Amazon Basin harbor most of the world's last indigenous
      peoples who have limited contact with encroaching colonists. Knowledge of the
      geographic distribution of these isolated groups is essential to assist with the
      development of immediate protections for vulnerable indigenous settlements. We
      used remote sensing to document the locations of 28 isolated villages within the
      four Brazilian states of Acre, Amazonas, Roraima, and Rondonia. The sites were
      confirmed during previous over-flights and by image evidence of thatched-roof
      houses; they are estimated to host over 1,700 individuals. Locational data were
      used to train maximum entropy models that identified landscape and anthropogenic
      features associated with the occurrence of isolated indigenous villages,
      including elevation, proximity to streams of five different orders, proximity to
      roads and settlements, proximity to recent deforestation, and vegetation cover
      type. Isolated villages were identified at mid elevations, within 20 km of the
      tops of watersheds and at greater distances from existing roads and trails. We
      further used model results, combined with boundaries of the existing indigenous
      territory system that is designed to protect indigenous lands, to assess the
      efficacy of the existing protected area network for isolated peoples. Results
      indicate that existing indigenous territories encompass all of the villages we
      identified, and 50% of the areas with high predicted probabilities of isolated
      village occurrence. Our results are intended to help inform policies that can
      mitigate against future external threats to isolated peoples. 

PMID- 25970613
TI  - Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its
      implications for disease control: two cohort studies.
AB  - BACKGROUND: Trachoma causes blindness through a conjunctival scarring process
      initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers
      and pathophysiological determinants are poorly understood. We investigated
      progressive scarring and its relationship to conjunctival infection, inflammation
      and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL
      FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of
      individuals with established trachomatous conjunctival scarring. They were
      followed six-monthly for two years, with clinical examinations and conjunctival
      swab sample collection. Progressive scarring cases were identified by comparing
      baseline and two-year photographs, and compared to individuals without
      progression. Samples were tested for C. trachomatis by PCR and transcript levels
      of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83
      were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585
      (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants.
      There was a strong relationship between progressive scarring and increasing
      inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR
      5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were
      detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort.
      Clinical inflammation, but not scarring progression, was associated with
      increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and
      reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of
      detectable C. trachomatis, which raises uncertainty about the primary drivers of
      late-stage trachoma. Chronic conjunctival inflammation appears to be central and
      is associated with enriched expression of pro-inflammatory factors and altered
      expression of extracellular matrix regulators. Host determinants of scarring
      progression appear more complex and subtle than the features of inflammation.
      Overall this indicates a potential role for anti-inflammatory interventions to
      interrupt progression and the need for trichiasis disease surveillance and
      surgery long after chlamydial infection has been controlled at community level.

PMID- 25970614
TI  - Cucurbitacin E Induces Autophagy via Downregulating mTORC1 Signaling and
      Upregulating AMPK Activity.
AB  - Cucurbitacins, the natural triterpenoids possessing many biological activities,
      have been reported to suppress the mTORC1/p70S6K pathway and to induce autophagy.
      However, the correlation between such activities is largely unknown. In this
      study, we addressed this issue in human cancer cells in response to cucurbitacin
      E (CuE) treatment. Our results showed that CuE induced autophagy as evidenced by
      the formation of LC3-II and colocalization of punctate LC3 with the lysosomal
      marker LAMP2 in HeLa and MCF7 cells. However, CuE induced much lower levels of
      autophagy in ATG5-knocked down cells and failed to induce autophagy in DU145
      cells lacking functional ATG5 expression, suggesting the dependence of CuE
      induced autophagy on ATG5. Consistent with autophagy induction, mTORC1 activity
      (as reflected by p70S6K and ULK1S758 phosphorylation) was inhibited by CuE
      treatment. The suppression of mTORC1 activity was further confirmed by reduced
      recruitment of mTOR to the lysosome, which is the activation site of mTORC1. In
      contrast, CuE rapidly activated AMPK leading to increased phosphorylation of its
      substrates. AMPK activation contributed to CuE-induced suppression of
      mTORC1/p70S6K signaling and autophagy induction, since AMPK knockdown diminished
      these effects. Collectively, our data suggested that CuE induced autophagy in
      human cancer cells at least partly via downregulation of mTORC1 signaling and
      upregulation of AMPK activity. 

PMID- 25970617
TI  - Timing and Spatial Distribution of Loess in Xinjiang, NW China.
AB  - Central Asia is one of the most significant loess regions on Earth, with an
      important role in understanding Quaternary climate and environmental change.
      However, in contrast to the widely investigated loess deposits in the Chinese
      Loess Plateau, the Central Asian loess-paleosol sequences are still
      insufficiently known and poorly understood. Through field investigation and
      review of the previous literature, the authors have investigated the
      distribution, thickness and age of the Xinjiang loess, and analyzed factors that
      control these parameters in the Xinjiang in northwest China, Central Asia. The
      loess sediments cover river terraces, low uplands, the margins of deserts and the
      slopes of the Tianshan Mountains and Kunlun Mountains and are also present in the
      Ili Basin. The thickness of the Xinjiang loess deposits varies from several
      meters to 670 m. The variation trend of the sand fraction (>63 MUm) grain-size
      contour can indicate the local major wind directions, so we conclude that the NW
      and NE winds are the main wind directions in the North and South Xinjiang, and
      the westerly wind mainly transport dust into the Ili basin. We consider
      persistent drying, adequate regional wind energy and well-developed river
      terraces to be the main factors controlling the distribution, thickness and
      formation age of the Xinjiang loess. The well-outcropped loess sections have
      mainly developed since the middle Pleistocene in Xinjiang, reflecting the
      appearance of the persistent drying and the present air circulation system.
      However, the oldest loess deposits are as old as the beginning of the Pliocene in
      the Tarim Basin, which suggests that earlier aridification occurred in the Tarim
      Basin rather than in the Ili Basin and the Junggar Basin. 

PMID- 25970615
TI  - Fibroblast Growth Factor Receptors (FGFRs) in Human Sperm: Expression,
      Functionality and Involvement in Motility Regulation.
AB  - Fibroblast growth factors receptors (FGFRs) have been widely characterized in
      somatic cells, but there is scarce evidence of their expression and function in
      mammalian gametes. The objective of the present study was to evaluate the
      expression of FGFRs in human male germ cells, to determine sperm FGFR activation
      by the FGF2 ligand and their participation in the regulation of sperm motility.
      The expression of FGFR1, 2, 3 and 4 mRNAs and proteins in human testis and
      localization of these receptors in germ cells of the seminiferous epithelium was
      demonstrated. In ejaculated sperm, FGFRs were localized to the acrosomal region
      and flagellum. Sperm exposure to FGF2 caused an increase in flagellar FGFR
      phosphorylation and activation of extracellular signal-regulated kinase (ERK) and
      protein kinase B (PKB or Akt) signaling pathways. Incubation with FGF2 led to a
      significant increase in the percentage of total and progressive sperm motility,
      as well as in sperm kinematics. All responses were prevented by sperm
      preincubation with BGJ398, a specific inhibitor of FGFR tyrosine kinase activity.
      In addition to confirming the expression of FGFRs in germ cells of the human
      testis, our study describes for the first time the presence, localization and
      functionality of human sperm FGFRs, and provides evidence of the beneficial
      effect of FGF2 upon sperm motility. 

PMID- 25970616
TI  - Hcn1 is a tremorgenic genetic component in a rat model of essential tremor.
AB  - Genetic factors are thought to play a major role in the etiology of essential
      tremor (ET); however, few genetic changes that induce ET have been identified to
      date. In the present study, to find genes responsible for the development of ET,
      we employed a rat model system consisting of a tremulous mutant strain, TRM/Kyo
      (TRM), and its substrain TRMR/Kyo (TRMR). The TRM rat is homozygous for the
      tremor (tm) mutation and shows spontaneous tremors resembling human ET. The TRMR
      rat also carries a homozygous tm mutation but shows no tremor, leading us to
      hypothesize that TRM rats carry one or more genes implicated in the development
      of ET in addition to the tm mutation. We used a positional cloning approach and
      found a missense mutation (c. 1061 C>T, p. A354V) in the hyperpolarization
      activated cyclic nucleotide-gated 1 channel (Hcn1) gene. The A354V HCN1 failed to
      conduct hyperpolarization-activated currents in vitro, implicating it as a loss
      of-function mutation. Blocking HCN1 channels with ZD7288 in vivo evoked kinetic
      tremors in nontremulous TRMR rats. We also found neuronal activation of the
      inferior olive (IO) in both ZD7288-treated TRMR and non-treated TRM rats and a
      reduced incidence of tremor in the IO-lesioned TRM rats, suggesting a critical
      role of the IO in tremorgenesis. A rat strain carrying the A354V mutation alone
      on a genetic background identical to that of the TRM rats showed no tremor.
      Together, these data indicate that body tremors emerge when the two mutant loci,
      tm and Hcn1A354V, are combined in a rat model of ET. In this model, HCN1 channels
      play an important role in the tremorgenesis of ET. We propose that oligogenic,
      most probably digenic, inheritance is responsible for the genetic heterogeneity
      of ET. 

PMID- 25970618
TI  - Assessment of patient empowerment--a systematic review of measures.
AB  - BACKGROUND: Patient empowerment has gained considerable importance but
      uncertainty remains about the best way to define and measure it. The validity of
      empirical findings depends on the quality of measures used. This systematic
      review aims to provide an overview of studies assessing psychometric properties
      of questionnaires purporting to capture patient empowerment, evaluate the
      methodological quality of these studies and assess the psychometric properties of
      measures identified. METHODS: Electronic searches in five databases were combined
      with reference tracking of included articles. Peer-reviewed articles reporting
      psychometric testing of empowerment measures for adult patients in French,
      German, English, Portuguese and Spanish were included. Study characteristics,
      constructs operationalised and psychometric properties were extracted. The
      quality of study design, methods and reporting was assessed using the COSMIN
      checklist. The quality of psychometric properties was assessed using Terwee's
      2007 criteria. FINDINGS: 30 studies on 19 measures were included. Six measures
      are generic, while 13 were developed for a specific condition (N=4) or specialty
      (N=9). Most studies tested measures in English (N=17) or Swedish (N=6). Sample
      sizes of included studies varied from N=35 to N=8261. A range of patient
      empowerment constructs was operationalised in included measures. These were
      classified into four domains: patient states, experiences and capacities; patient
      actions and behaviours; patient self-determination within the healthcare
      relationship and patient skills development. Quality assessment revealed several
      flaws in methodological study quality with COSMIN scores mainly fair or poor. The
      overall quality of psychometric properties of included measures was intermediate
      to positive. Certain psychometric properties were not tested for most measures.
      DISCUSSION: Findings provide a basis from which to develop consensus on a core
      set of patient empowerment constructs and for further work to develop a (set of)
      appropriately validated measure(s) to capture this. The methodological quality of
      psychometric studies could be improved by adhering to published quality criteria.

PMID- 25970619
TI  - Accuracy of Two Motor Assessments during the First Year of Life in Preterm
      Infants for Predicting Motor Outcome at Preschool Age.
AB  - AIM: The primary aim of this study was to investigate the accuracy of the Alberta
      Infant Motor Scale (AIMS) and Neuro-Sensory Motor Developmental Assessment
      (NSMDA) over the first year of life for predicting motor impairment at 4 years in
      preterm children. The secondary aims were to assess the predictive value of
      serial assessments over the first year and when using a combination of these two
      assessment tools in follow-up. METHOD: Children born <30 weeks' gestation were
      prospectively recruited and assessed at 4, 8 and 12 months' corrected age using
      the AIMS and NSMDA. At 4 years' corrected age children were assessed for cerebral
      palsy (CP) and motor impairment using the Movement Assessment Battery for
      Children 2nd-edition (MABC-2). We calculated accuracy of the AIMS and NSMDA for
      predicting CP and MABC-2 scores <=15th (at-risk of motor difficulty) and <=5th
      centile (significant motor difficulty) for each test (AIMS and NSMDA) at 4, 8 and
      12 months, for delay on one, two or all three of the time points over the first
      year, and finally for delay on both tests at each time point. RESULTS: Accuracy
      for predicting motor impairment was good for each test at each age, although
      false positives were common. Motor impairment on the MABC-2 (scores <=5th and
      <=15th) was most accurately predicted by the AIMS at 4 months, whereas CP was
      most accurately predicted by the NSMDA at 12 months. In regards to serial
      assessments, the likelihood ratio for motor impairment increased with the number
      of delayed assessments. When combining both the NSMDA and AIMS the best accuracy
      was achieved at 4 months, although results were similar at 8 and 12 months.
      INTERPRETATION: Motor development during the first year of life in preterm
      infants assessed with the AIMS and NSMDA is predictive of later motor impairment
      at preschool age. However, false positives are common and therefore it is
      beneficial to follow-up children at high risk of motor impairment at more than
      one time point, or to use a combination of assessment tools. TRIAL REGISTRATION:
      ACTR.org.au ACTRN12606000252516.

PMID- 25970621
TI  - Potential for worldwide displacement of fossil-fuel electricity by nuclear energy
      in three decades based on extrapolation of regional deployment data.
AB  - There is an ongoing debate about the deployment rates and composition of
      alternative energy plans that could feasibly displace fossil fuels globally by
      mid-century, as required to avoid the more extreme impacts of climate change.
      Here we demonstrate the potential for a large-scale expansion of global nuclear
      power to replace fossil-fuel electricity production, based on empirical data from
      the Swedish and French light water reactor programs of the 1960s to 1990s.
      Analysis of these historical deployments show that if the world built nuclear
      power at no more than the per capita rate of these exemplar nations during their
      national expansion, then coal- and gas-fired electricity could be replaced
      worldwide in less than a decade. Under more conservative projections that take
      into account probable constraints and uncertainties such as differing relative
      economic output across regions, current and past unit construction time and
      costs, future electricity demand growth forecasts and the retiring of existing
      aging nuclear plants, our modelling estimates that the global share of fossil
      fuel-derived electricity could be replaced within 25-34 years. This would allow
      the world to meet the most stringent greenhouse-gas mitigation targets. 

PMID- 25970620
TI  - Involvement of B2 receptor in bradykinin-induced proliferation and
      proinflammatory effects in human nasal mucosa-derived fibroblasts isolated from
      chronic rhinosinusitis patients.
AB  - Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal
      mucosa either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP).
      CRSsNP accounts for the majority of CRS cases and is characterized by fibrosis
      and neutrophilic inflammation. However, the pathogenesis of CRS, especially
      CRSsNP, remains unclear. Immunohistochemistry of CRSsNP specimens in the present
      study showed that the submucosa, perivascular areas, and the mucous glands were
      abundant in fibroblasts. Therefore, we investigated the effects bradykinin (BK),
      an autacoid known to participate in inflammation, on human CRSsNP nasal mucosa
      derived fibroblasts (NMDFs). BK increased CXCL1 and -8 secretion and mRNA
      expression with EC50 ranging from 0.15~0.35 MUM. Moreover, BK enhanced cell
      proliferation and upregulated the expressions of proinflammatory molecules,
      including cell adhesion molecules (CAMs) and cyclooxygenase (COX)-1 and -2. These
      functionally caused an increase in monocyte adhesion to fibroblast monolayer.
      Using pharmacological intervention and BKR siRNA knockdown, we demonstrated that
      the BK-induced CXCL chemokine release, cell proliferation and COX and CAM
      expressions were mainly through the B2 receptor (B2R). Accordingly, the B2R was
      preferentially expressed in the NMDFs than B1R. The B2R was highly expressed in
      the CRSsNP than the control specimens, while the B1R and kininogen (KNG)/BK
      expression slightly increased in the CRSsNP mucosa. Collectively, we report here
      for the first time that fibroblasts, KNG/BK, and BKRs are overexpressed in CRSsNP
      mucosa and BK upregulates chemokine expression, proliferation, and
      proinflammatory molecule expression in NMDFs via B2R activation, which lead to a
      functional increase in monocyte-fibroblast interaction. Our findings reveal a
      critical role of fibroblast, KNG/BK, and BKRs in the development of CRSsNP. 

PMID- 25970622
TI  - Different Dynamic Patterns of beta-Lactams, Quinolones, Glycopeptides and
      Macrolides on Mouse Gut Microbial Diversity.
AB  - The adverse impact of antibiotics on the gut microbiota has attracted extensive
      interest, particularly due to the development of microbiome research techniques
      in recent years. However, a direct comparison of the dynamic effects of various
      types of antibiotics using the same animal model has not been available. In the
      present study, we selected six antibiotics from four categories with the broadest
      clinical usage, namely, beta-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam
      and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and
      macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected
      during and after the administration of antibiotics, and microbial diversity was
      analyzed through Illumina sequencing and bioinformatics analyses using QIIME.
      Both alpha and beta diversity analyses showed that ceftriaxone sodium,
      cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota
      dramatically by the second day of antibiotic administration whereas the influence
      of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but
      much less than vancomycin and the beta-lactams. In general, the community changes
      induced by the three beta-lactam antibiotics showed consistency in inhibiting
      Papillibacter, Prevotella and Alistipes while inducing massive growth of
      Clostridium. The low diversity and high Clostridium level might be an important
      cause of Clostridium difficile infection after usage of beta-lactams. Vancomycin
      was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the
      other hand, it induced the growth of Escherichia and effect lasted for months
      afterward. Azithromycin and meropenem induced the growth of Enterococcus. These
      findings will be useful for understanding the potential adverse effects of
      antibiotics on the gut microbiome and ensuring their better usage. 

PMID- 25970623
TI  - Differential regulation of the high-affinity choline transporter by wild-type and
      Swedish mutant amyloid precursor protein.
AB  - The high-affinity choline transporter (CHT) is responsible for choline uptake
      into cholinergic neurons, with this being the rate-limiting step for
      acetylcholine production. Altering CHT protein disposition directly impacts
      choline uptake activity and cholinergic neurotransmission. Amyloid precursor
      protein (APP) interacts with CHT proteins and increases their endocytosis from
      the cell surface. The goal of this study was to examine regulation of CHT
      trafficking and activity by wild-type APP (APPwt) and determine if this differs
      with Swedish mutant APP (APPSwe) in SH-SY5Y human neuroblastoma cells. APPSwe
      differs from APPwt in its trafficking from the cell surface through endosomes. We
      report for the first time that CHT interacts significantly less with APPSwe than
      with APPwt. Surprisingly, however, CHT cell surface levels and choline uptake
      activity are decreased to the same extent and CHT co-localization to early
      endosomes increased similarly in cells expressing either APPwt or APPSwe. A
      critical observation is that CHT co-immunoprecipitates with betaCTF from APPSwe
      expressing cells. We propose that decreased CHT function is mediated differently
      by APPwt and APPSwe; APPwt interaction with CHT facilitates its endocytosis from
      the cell surface, whereas the effect of APPSwe on CHT is mediated indirectly
      potentially by binding to the betaCTF fragment or by Abeta released from cells.
      High-affinity choline transporter (CHT) takes choline into cholinergic neurons
      for acetylcholine synthesis. Amyloid precursor protein (APP) interacts with CHT
      proteins, but this is decreased for Swedish mutant APP (APPSwe). CHT cell surface
      levels and localization to early endosomes, and choline uptake activity are
      changed similarly by APPwt or APPSwe. APPSwe mediates effects indirectly
      potentially by betaCTF or Abeta.

PMID- 25970624
TI  - Adoption in eastern grey kangaroos: a consequence of misdirected care?
AB  - Adoption is rare in animals and is usually attributed to kin selection. In a 6
      year study of eastern grey kangaroos (Macropus giganteus), 11 of 326 juveniles
      were adopted. We detected eight adoptions by observing behavioural associations
      and nursing between marked mothers and young and three more by analysing the
      relatedness of mothers and young using microsatellite DNA. Four adoptions
      involved reciprocal switches and three were by mothers whose own pouch young were
      known to subsequently disappear. Adoptive mothers were not closely related to
      each other or to adoptees but adoptive mothers and young associated as closely as
      did biological pairs, as measured by half-weight indices. Switch mothers did not
      associate closely. Maternal age and body condition did not influence the
      likelihood of adoption but females were more likely to adopt in years with high
      densities of females with large pouch young. Adoption did not improve juvenile
      survival. We conclude that adoptions in this wild population were potentially
      costly and likely caused by misdirected care, suggesting that eastern grey
      kangaroos may have poorly developed mother-offspring recognition mechanisms. 

PMID- 25970625
TI  - Surgical risks associated with winter sport tourism.
AB  - BACKGROUND: Mass tourism during winter in mountain areas may cause significant
      clustering of body injuries leading to increasing emergency admissions at
      hospital. We aimed at assessing if surgical safety and efficiency was maintained
      in this particular context. METHODS: We selected all emergency admissions of open
      surgery performed in French hospitals between 2010 and 2012. After identifying
      mountain areas with increasing volume of surgical stays during winter, we
      considered seasonal variations in surgical outcomes using a difference-in
      differences study design. We computed multilevel regressions to evaluate whether
      significant increase in emergency cases had an effect on surgical mortality,
      complications and length of stay. Clustering effect of patients within hospitals
      was integrated in analysis and surgical outcomes were adjusted for both patient
      and hospital characteristics. RESULTS: A total of 381 hospitals had 559,052
      inpatient stays related to emergency open surgery over 3 years. Compared to other
      geographical areas, a significant peak of activity was noted during winter in
      mountainous hospitals (Alps, Pyrenees, Vosges), ranging 6-77% volume increase.
      Peak was mainly explained by tourists' influx (+124.5%, 4,351/3,496) and
      increased need for orthopaedic procedures (+36.8%, 4,731/12,873). After
      controlling for potential confounders, patients did not experience increased risk
      for postoperative death (ratio of OR 1.01, 95%CI 0.89-1.14, p = 0.891),
      thromboembolism (0.95, 0.77-1.17, p = 0.621) or sepsis (0.98, 0.85-1.12, p =
      0.748). Length of stay was unaltered (1.00, 0.99-1.02, p = 0.716). CONCLUSION:
      Surgical outcomes are not compromised during winter in French mountain areas
      despite a substantial influx of major emergencies.

PMID- 25970626
TI  - FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1
      Complex.
AB  - The ubiquitin-proteasome system for protein degradation plays a major role in
      regulating cell function and many signaling proteins are tightly controlled by
      this mechanism. Among these, Regulator of G Protein Signaling 2 (RGS2) is a
      target for rapid proteasomal degradation, however, the specific enzymes involved
      are not known. Using a genomic siRNA screening approach, we identified a novel E3
      ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1 (DDB1)
      and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation. While the
      more typical F-box partners CUL1 and Skp1 can bind FBXO44, that E3 ligase complex
      does not bind RGS2 and is not involved in RGS2 degradation. These observations
      define an unexpected DDB1/CUL4B-containing FBXO44 E3 ligase complex.
      Pharmacological targeting of this mechanism provides a novel therapeutic approach
      to hypertension, anxiety, and other diseases associated with RGS2 dysregulation. 

PMID- 25970628
TI  - The complete mitochondrial genome of the rocky reef fish Cheilodactylus
      variegatus Valenciennes, 1833 (Teleostei: Cheilodactylidae).
AB  - Cheilodactylus variegatus is a common benthivorous marine fish inhabiting in
      rocky subtidal habitats in the eastern south Pacific coast of Chile and Peru.
      However, its biology and ecology are relatively understudied and its taxonomic
      assignment has been debated recently. The complete mitochondrial genome was
      assembled de novo and mapped to a reference using 5.97 million of reads obtained
      through Ion Torrent next generation sequencing, resulting in a circular sequence
      of 16,652 bp in length. Gene composition and arrangement comprised to that
      reported for most fishes and contained the typical structure of 2 rRNAs, 13
      protein-coding genes, 22 tRNAs and 1 non-coding region. This mitogenome provides
      a valuable resource for studies of fish molecular systematics, phylogeography and
      population genetics.

PMID- 25970627
TI  - Auxin Import and Local Auxin Biosynthesis Are Required for Mitotic Divisions,
      Cell Expansion and Cell Specification during Female Gametophyte Development in
      Arabidopsis thaliana.
AB  - The female gametophyte of flowering plants, called the embryo sac, develops from
      a haploid cell named the functional megaspore, which is specified after meiosis
      by the diploid sporophyte. In Arabidopsis, the functional megaspore undergoes
      three syncitial mitotic divisions followed by cellularization to form seven cells
      of four cell types including two female gametes. The plant hormone auxin is
      important for sporophytic developmental processes, and auxin levels are known to
      be regulated by biosynthesis and transport. Here, we investigated the role of
      auxin biosynthetic genes and auxin influx carriers in embryo sac development. We
      find that genes from the YUCCA/TAA pathway (YUC1, YUC2, YUC8, TAA1, TAR2) are
      expressed asymmetrically in the developing ovule and embryo sac from the two
      nuclear syncitial stage until cellularization. Mutants for YUC1 and YUC2
      exhibited defects in cell specification, whereas mutations in YUC8, as well as
      mutations in TAA1 and TAR2, caused defects in nuclear proliferation, vacuole
      formation and anisotropic growth of the embryo sac. Additionally, expression of
      the auxin influx carriers AUX1 and LAX1 were observed at the micropylar pole of
      the embryo sac and in the adjacent cells of the ovule, and the aux1 lax1 lax2
      triple mutant shows multiple gametophyte defects. These results indicate that
      both localized auxin biosynthesis and auxin import, are required for mitotic
      divisions, cell expansion and patterning during embryo sac development. 

PMID- 25970629
TI  - Early percutaneous endoscopic gastrostomy tube dislodgment.
AB  - OVERVIEW: The authors present a case of early percutaneous endoscopic gastrostomy
      tube dislodgment, attempted replacement, and subsequent sepsis that resulted in
      the patient's death. Gastrostomy techniques, complications, preventive
      strategies, and proper tube management are addressed.

PMID- 25970630
TI  - Epilepsy update, part 2: nursing care and evidence-based treatment.
AB  - OVERVIEW: As new research has increased our understanding of epilepsy and the
      challenges patients with epilepsy face, the role of the nurse as an educator and
      advocate has grown. This article, the second in a two-part series, addresses the
      most important aspects of assessing and caring for patients with epilepsy
      highlighting the seizure first-aid instructions that all family members of a
      patient with epilepsy should have; the teaching points to share with parents of
      young children with epilepsy; and online epilepsy resources for patients, family
      members, and health care professionals. The authors also discuss current medical,
      surgical, neurostimulatory, and dietary approaches to epilepsy treatment.

PMID- 25970631
TI  - Switching from Clopidogrel to Prasugrel in patients undergoing PCI: A meta
      analytic overview.
AB  - Despite the demonstrated benefits of Prasugrel, a new generation thienopyridine,
      in the prevention of thrombotic complications after percutaneous coronary
      interventions (PCI) for Acute Coronary Syndromes (ACS), its use is still
      precluded to those many patients arriving to the cath lab pre-treated with
      Clopidogrel. Conclusive data on the strategy of switching from Clopidogrel to
      Prasugrel are still missing, therefore we aimed to perform a meta-analysis of
      current studies evaluating the safety and efficacy of switching from Clopidogrel
      to Prasugrel (PS) as compared to a standard thienopyridine therapy with
      Clopidogrel or Prasugrel in patients undergoing PCI. Literature archives and main
      scientific sessions' abstracts were scanned for studies comparing a switching
      strategy from Clopidogrel to Prasugrel vs. Prasugrel or Clopidogrel. Primary
      efficacy endpoint was overall mortality. Secondary endpoints were: non-fatal
      myocardial infarction and definite/probable stent thrombosis. Safety endpoint was
      the rate of major bleedings according to a per-protocol definition. A total of 12
      studies, involving 3956 patients, were included. Among them, 1396 patients
      (35.3%), received Prasugrel after a Clopidogrel treatment (PS), while 2560
      (64.7%) received either Prasugrel or Clopidogrel. The switch from Clopidogrel to
      Prasugrel was in the majority of the studies periprocedural. The mortality was
      numerically lower, but not statistically significant, in the PS group as compared
      with patients who did not switch (1.7% vs. 3.8%, OR [95% CI] = 0.68 [0.40,1.15],
      p = 0.15, phet = 0.61), without any relationship with patients' risk profile (r =
      -0.68 [-2.09, 0.73], p = 0.35). Similar results were obtained for secondary
      efficacy endpoints and at sensitivity analysis in the majority of subgroups
      evaluated. Moreover, the PS strategy did not increase major bleedings as compared
      with standard therapy (1.4% vs. 2.5%, OR [95% CI = 0.70 [0.39, 1.25], p = 0.23,
      phet = 0.6). The present meta-analysis confirms that, among patients undergoing
      PCI, switching from Clopidogrel to Prasugrel may be safely performed and
      therefore should be encouraged among patients eligible to Prasugrel.

PMID- 25970632
TI  - Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to
      Clinical Outcome in Patients on Maraviroc.
AB  - OBJECTIVES: We analysed the impact of different parameters on genotypic tropism
      testing related to clinical outcome prediction in 108 patients on maraviroc (MVC)
      treatment. METHODS: 87 RNA and 60 DNA samples were used. The viral tropism was
      predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs
      ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in
      triplicate, 43 samples with the ESTA assay and 45 with next-generation
      sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC
      resistance mutations on clinical outcome was also studied. RESULTS: Concordance
      between single-amplification testing compared to ESTA and to NGS was in the order
      of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of
      baseline R5 viruses in RNA and DNA samples by all methods significantly
      correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple
      amplification did not improve the prediction value but reduced the number of
      patients eligible for MVC. No influence of the GSS or MVC-resistance mutations
      but adherence to treatment, on the clinical outcome was detected. CONCLUSIONS:
      Proviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%
      7.5% and single amplification from RNA or DNA would assure a safe administration
      of MVC without excluding many patients who could benefit from this drug. In
      addition, the new prediction system T-CUP produced reliable results.

PMID- 25970633
TI  - Aging in Sensory and Motor Neurons Results in Learning Failure in Aplysia
      californica.
AB  - The physiological and molecular mechanisms of age-related memory loss are
      complicated by the complexity of vertebrate nervous systems. This study takes
      advantage of a simple neural model to investigate nervous system aging, focusing
      on changes in learning and memory in the form of behavioral sensitization in vivo
      and synaptic facilitation in vitro. The effect of aging on the tail withdrawal
      reflex (TWR) was studied in Aplysia californica at maturity and late in the
      annual lifecycle. We found that short-term sensitization in TWR was absent in
      aged Aplysia. This implied that the neuronal machinery governing nonassociative
      learning was compromised during aging. Synaptic plasticity in the form of short
      term facilitation between tail sensory and motor neurons decreased during aging
      whether the sensitizing stimulus was tail shock or the heterosynaptic modulator
      serotonin (5-HT). Together, these results suggest that the cellular mechanisms
      governing behavioral sensitization are compromised during aging, thereby nearly
      eliminating sensitization in aged Aplysia. 

PMID- 25970634
TI  - Gender Differences in Mental Health Outcomes before, during, and after the Great
      Recession.
AB  - We examined gender differences in mental health outcomes during and post
      recession versus pre-recession. We utilized 2005-2006, 2008-2009, and 2010-2011
      data from the Medical Expenditure Panel Survey. Females had lower odds of
      depression diagnoses during and post-recession and better mental health during
      the recession, but higher odds of anxiety diagnoses post-recession. Males had
      lower odds of depression diagnoses and better mental health during and post
      recession and lower Kessler 6 scores post-recession. We conducted stratified
      analyses, which confirmed that the aforementioned findings were consistent across
      the four different regions of the U.S., by employment status, income and health
      care utilization. Importantly, we found that the higher odds of anxiety diagnoses
      among females after the recession were mainly prominent among specific subgroups
      of females: those who lived in the Northeast or the Midwest, the unemployed, and
      those with low household income. Gender differences in mental health in
      association with the economic recession highlight the importance of policymakers
      taking these differences into consideration when designing economic and social
      policies to address economic downturns. Future research should examine the
      reasons behind the decreased depression diagnoses among both genders, and whether
      they signify decreased mental healthcare utilization or increased social support
      and more time for exercise and leisure activities. 

PMID- 25970635
TI  - High resolution mapping of enhancer-promoter interactions.
AB  - RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a
      profiled cell type and the genes that the enhancers regulate through chromatin
      interactions. The most commonly used computational method for analyzing ChIA-PET
      data, the ChIA-PET Tool, discovers interaction anchors at a spatial resolution
      that is insufficient to accurately identify individual enhancers. We introduce
      Germ, a computational method that estimates the likelihood that any two narrowly
      defined genomic locations are jointly occupied by RNA Polymerase II. Germ takes a
      blind deconvolution approach to simultaneously estimate the likelihood of RNA
      Polymerase II occupation as well as a model of the arrangement of read alignments
      relative to locations occupied by RNA Polymerase II. Both types of information
      are utilized to estimate the likelihood that RNA Polymerase II jointly occupies
      any two genomic locations. We apply Germ to RNA Polymerase II ChIA-PET data from
      embryonic stem cells to identify the genomic locations that are jointly occupied
      along with transcription start sites. We show that these genomic locations align
      more closely with features of active enhancers measured by ChIP-Seq than the
      locations identified using the ChIA-PET Tool. We also apply Germ to RNA
      Polymerase II ChIA-PET data from motor neuron progenitors. Based on the Germ
      results, we observe that a combination of cell type specific and cell type
      independent regulatory interactions are utilized by cells to regulate gene
      expression. 

PMID- 25970636
TI  - Two Scaffolds from Two Flips: (alpha,beta)/(beta,gamma) CH2/NH "Met-Im" Analogues
      of dTTP.
AB  - Novel alpha,beta-CH2 and beta,gamma-NH (1a) or alpha,beta-NH and beta,gamma-CH2
      (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl
      phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]
      rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl
      phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS)
      deprotection after Mitsunobu conjugation with dT was avoided by microwave
      conditions. 1a was 9-fold more potent in inhibiting DNA polymerase beta,
      attributed to an NH-group interaction with R183 in the active site. 

PMID- 25970637
TI  - Mandible-Powered Escape Jumps in Trap-Jaw Ants Increase Survival Rates during
      Predator-Prey Encounters.
AB  - Animals use a variety of escape mechanisms to increase the probability of
      surviving predatory attacks. Antipredator defenses can be elaborate, making their
      evolutionary origin unclear. Trap-jaw ants are known for their rapid and powerful
      predatory mandible strikes, and some species have been observed to direct those
      strikes at the substrate, thereby launching themselves into the air away from a
      potential threat. This potential escape mechanism has never been examined in a
      natural context. We studied the use of mandible-powered jumping in Odontomachus
      brunneus during their interactions with a common ant predator: pit-building
      antlions. We observed that while trap-jaw ant workers escaped from antlion pits
      by running in about half of interactions, in 15% of interactions they escaped by
      mandible-powered jumping. To test whether escape jumps improved individual
      survival, we experimentally prevented workers from jumping and measured their
      escape rate. Workers with unrestrained mandibles escaped from antlion pits
      significantly more frequently than workers with restrained mandibles. Our results
      indicate that some trap-jaw ant species can use mandible-powered jumps to escape
      from common predators. These results also provide a charismatic example of
      evolutionary co-option, where a trait that evolved for one function (predation)
      has been co-opted for another (defense). 

PMID- 25970638
TI  - Strain-Specific Interactions of Listeria monocytogenes with the Autophagy System
      in Host Cells.
AB  - Listeria monocytogenes is an intracellular bacterial pathogen that can replicate
      in the cytosol of host cells. These bacteria undergo actin-based motility in the
      cytosol via expression of ActA, which recruits host actin-regulatory proteins to
      the bacterial surface. L. monocytogenes is thought to evade killing by autophagy
      using ActA-dependent mechanisms. ActA-independent mechanisms of autophagy evasion
      have also been proposed, but remain poorly understood. Here we examined autophagy
      of non-motile (DeltaactA) mutants of L. monocytogenes strains 10403S and EGD-e,
      two commonly studied strains of this pathogen. The DeltaactA mutants displayed
      accumulation of ubiquitinated proteins and p62/SQSTM1 on their surface. However,
      only strain EGD-e DeltaactA displayed colocalization with the autophagy marker
      LC3 at 8 hours post infection. A bacteriostatic agent (chloramphenicol) was
      required for LC3 recruitment to 10403S DeltaactA, suggesting that these bacteria
      produce a factor for autophagy evasion. Internalin K was proposed to block
      autophagy of L. monocytogenes in the cytosol of host cells. However, deletion of
      inlK in either the wild-type or DeltaactA background of strain 10403S had no
      impact on autophagy evasion by bacteria, indicating it does not play an essential
      role in evading autophagy. Replication of DeltaactA mutants of strain EGD-e and
      10403S was comparable to their parent wild-type strain in macrophages. Thus,
      DeltaactA mutants of L. monocytogenes can block killing by autophagy at a step
      downstream of protein ubiquitination and, in the case of strain EGD-e, downstream
      of LC3 recruitment to bacteria. Our findings highlight the strain-specific
      differences in the mechanisms that L. monocytogenes uses to evade killing by
      autophagy in host cells. 

PMID- 25970639
TI  - Warfarin pharmacogenetics in the era of new oral anticoagulants.

PMID- 25970640
TI  - Post-Spaceflight (STS-135) Mouse Splenocytes Demonstrate Altered Activation
      Properties and Surface Molecule Expression.
AB  - Alterations in immune function have been documented during or post-spaceflight
      and in ground based models of microgravity. Identification of immune parameters
      that are dysregulated during spaceflight is an important step in mitigating crew
      health risks during deep space missions. The in vitro analysis of leukocyte
      activity post-spaceflight in both human and animal species is primarily focused
      on lymphocytic function. This report completes a broader spectrum analysis of
      mouse lymphocyte and monocyte changes post 13 days orbital flight (mission STS
      135). Analysis includes an examination in surface markers for cell activation,
      and antigen presentation and co-stimulatory molecules. Cytokine production was
      measured after stimulation with T-cell mitogen or TLR-2, TLR-4, or TLR-5
      agonists. Splenocyte surface marker analysis immediate post-spaceflight and after
      in vitro culture demonstrated unique changes in phenotypic populations between
      the flight mice and matched treatment ground controls. Post-spaceflight
      splenocytes (flight splenocytes) had lower expression intensity of CD4+CD25+ and
      CD8+CD25+ cells, lower percentage of CD11c+MHC II+ cells, and higher percentage
      of CD11c+MHC I+ populations compared to ground controls. The flight splenocytes
      demonstrated an increase in phagocytic activity. Stimulation with ConA led to
      decrease in CD4+ population but increased CD4+CD25+ cells compared to ground
      controls. Culturing with TLR agonists led to a decrease in CD11c+ population in
      splenocytes isolated from flight mice compared to ground controls. Consequently,
      flight splenocytes with or without TLR-agonist stimulation showed a decrease in
      CD11c+MHC I+, CD11c+MHC II+, and CD11c+CD86+ cells compared to ground controls.
      Production of IFN-gamma was decreased and IL-2 was increased from ConA stimulated
      flight splenocytes. This study demonstrated that expression of surface molecules
      can be affected by conditions of spaceflight and impaired responsiveness persists
      under culture conditions in vitro. 

PMID- 25970641
TI  - Interactions between Chitosan and Alginate Dialdehyde Biopolymers and Their Layer
      by-Layer Assemblies.
AB  - Biopolymers are researched extensively for their applications in biomaterials
      science and drug delivery including structures and complexes of more than one
      polymer. Chemical characterization of complexes formed between chitosan (CHI) and
      alginate dialdehyde (ADA) biopolymers established that while electrostatic
      interactions dominate (as determined from X-ray photoelectron spectroscopy (XPS))
      covalent cross-linking between these biopolymers also contribute to their
      stability (evidenced from immersion in salt solution). It was furthermore found
      that imine bond formation could not be directly detected by any of the techniques
      XPS, FTIR, (1)H NMR, or fluorescence. The layer-by-layer assemblies of the
      biopolymers formed on silica colloids, glass slides, and alginate hydrogel beads
      were evaluated using XPS, as well as zeta potential measurements for the silica
      colloids and changes to hydration properties for the hydrogels. It was found that
      the degree of oxidation of ADA affected the LbL assemblies in terms of a greater
      degree of CHI penetration observed when using the more conformationally flexible
      biopolymer ADA (higher degree of oxidation). 

PMID- 25970643
TI  - Herpes zoster granulomatous dermatitis: histopathologic findings in a case
      series.
AB  - Several types of cutaneous reactions have been reported to arise at the site of
      herpes zoster (HZ) infection weeks to years after the acute disease. Among these,
      granulomatous reactions are the most frequently reported. In this study, we
      describe the spectrum of histopathologic findings of HZ granulomatous reactions
      observed in 26 patients with cutaneous lesions confined to the area of previous
      HZ eruption and compare them with biopsy specimens taken from 25 patients with
      acute HZ. All patients with persistent reactions from whom history was available
      presented within 12 weeks of the onset of the acute eruption. The most frequent
      findings were interstitial granulomatous dermatitis with lymphocytes, histiocytes
      and multinucleated giant cells displaying elastophagocytosis and a perineural,
      perivascular and perieccrine mononuclear inflammatory infiltrate rich in
      lymphocytes and plasma cells. Less common features included intra-arrector and
      peri-arrector pili granulomas, follicular dilatation and hyperkeratosis, and
      vasculitis. Specimens from patients with acute HZ were found to have small
      numbers of perineural plasma cells and most had subtle granulomatous
      inflammation, in patterns similar to the group with late granulomatous reactions.
      Our findings suggest that granulomatous reactions to varicella zoster virus
      represent a persistent evolving inflammatory reaction after acute infection. 

PMID- 25970642
TI  - The Phosphate Transporter Gene OsPht1;4 Is Involved in Phosphate Homeostasis in
      Rice.
AB  - A total of 13 phosphate transporters in rice (Oryza sative) have been identified
      as belonging to the Pht1 family, which mediates inorganic phosphate (Pi) uptake
      and transport. We report the biological property and physiological role of
      OsPht1;4 (OsPT4). Overexpressing OsPT4 resulted in significant higher Pi
      accumulation in roots, straw and brown rice, and suppression of OsPT4 caused
      decreased Pi concentration in straw and brown rice. Expression of the beta
      glucuronidase reporter gene driven by the OsPT4 promoter showed that OsPT4 is
      expressed in roots, leaves, ligules, stamens, and caryopses under sufficient Pi
      conditions, consistent with the expression profile showing that OsPT4 has high
      expression in roots and flag leaves. The transcript level of OsPT4 increased
      significantly both in shoots and roots with a long time Pi starvation. OsPT4
      encoded a plasma membrane-localized protein and was able to complement the
      function of the Pi transporter gene PHO84 in yeast. We concluded that OsPT4 is a
      functional Pi-influx transporter involved in Pi absorption in rice that might
      play a role in Pi translocation. This study will enrich our understanding about
      the physiological function of rice Pht1 family genes. 

PMID- 25970644
TI  - Standards in Dermatologic Imaging.

PMID- 25970646
TI  - Inspiratory muscle loading: a new approach for lowering glucose levels and
      glucose variability in patients with Type 2 diabetes.

PMID- 25970647
TI  - Advances in mass spectrometric characterization of naphthenic acids fraction
      compounds in oil sands environmental samples and crude oil--A review.
AB  - There has been a recent surge in the development of mass spectrometric methods
      for detailed characterization of naphthenic acid fraction compounds (all
      C(c)H(h)N(n)O(o)S(s), species, including heteroatomic and aromatic components in
      the acid-extractable fraction) in environmental samples. This surge is driven by
      the increased activity in oil sands environmental monitoring programs in Canada,
      the exponential increase in research studies on the isolation and toxicity
      identification of components in oil sands process water (OSPW), and the
      analytical requirements for development of technologies for treatment of OSPW.
      There has been additional impetus due to the parallel studies to control
      corrosion from naphthenic acids during the mining and refining of heavy bitumen
      and crude oils. As a result, a range of new mass spectrometry tools have been
      introduced since our last major review of this topic in 2009. Of particular
      significance are the developments of combined mass spectrometric methods that
      incorporate technologies such as gas chromatography, liquid chromatography, and
      ion mobility. There has been additional progress with respect to improved
      visualization methods for petroleomics and oil sands environmental forensics. For
      comprehensive coverage and more reliable characterization of samples, an approach
      based on multiple-methods that employ two or more ionization modes is
      recommended. On-line or off-line fractionation of isolated extracts, with or
      without derivatization, might also be used prior to mass spectrometric analyses.
      Individual ionization methods have their associated strengths and weaknesses,
      including biases, and thus dependence upon a single ionization method is
      potentially misleading. There is also a growing trend to not rely solely on low
      resolution mass spectrometric methods (<20,000 resolving power at m/z 200) for
      characterization of complex samples. Future research is anticipated to focus upon
      (i) structural elucidation of components to determine the correlation with
      toxicity or corrosion, (ii) verification of characterization studies based on
      authentic reference standards and reference materials, and (iii) integrated
      approaches based on multiple-methods and ionization methods for more-reliable oil
      sands environmental forensics.

PMID- 25970645
TI  - Physiologically inspired cardiac scaffolds for tailored in vivo function and
      heart regeneration.
AB  - Tissue engineering is well suited for the treatment of cardiac disease due to the
      limited regenerative capacity of native cardiac tissue and the loss of function
      associated with endemic cardiac pathologies, such as myocardial infarction and
      congenital heart defects. However, the physiological complexity of the myocardium
      imposes extensive requirements on tissue therapies intended for these
      applications. In recent years, the field of cardiac tissue engineering has been
      characterized by great innovation and diversity in the fabrication of engineered
      tissue scaffolds for cardiac repair and regeneration to address these problems.
      From early approaches that attempted only to deliver cardiac cells in a hydrogel
      vessel, significant progress has been made in understanding the role of each
      major component of cardiac living tissue constructs (namely cells, scaffolds, and
      signaling mechanisms) as they relate to mechanical, biological, and electrical in
      vivo performance. This improved insight, accompanied by modern material science
      techniques, allows for the informed development of complex scaffold materials
      that are optimally designed for cardiac applications. This review provides a
      background on cardiac physiology as it relates to critical cardiac scaffold
      characteristics, the degree to which common cardiac scaffold materials fulfill
      these criteria, and finally an overview of recent in vivo studies that have
      employed this type of approach. 

PMID- 25970648
TI  - Spin Crossover, Reversible Redox, and Supramolecular Interactions in 3d Complexes
      of 4-(4-Pyridyl)-2,5-dipyrazyl-pyridine.
AB  - A new terpyridine-inspired terdentate ligand, 4-(4-pyridyl)-2,5-dipyrazyl
      pyridine (py-pzpypz), featuring three "spare" nitrogen donors "out the back", has
      been used to synthesize five bis-ligand complexes, [M(II)(py-pzpypz)2]X2, where M
      = Mn with X = ClO4, or M = Fe, Co, Ni, and Zn with X = BF4. In contrast, when M =
      Cu(II), regardless of the M:L ratio employed, 1:1 M:L products were obtained: for
      X = BF4 a 1D chain {[Cu(II)(py-pzpypz)(DMF)2](BF4)2}n, and for X = Cl a
      monometallic complex [Cu(py-pzpypz)Cl2]. All seven complexes were structurally
      characterized, confirming the expected N6 coordination of the M(II) centers in
      all cases except Cu(II). Notably, a Jahn-Teller elongation is observed in the
      Co(II) complex, consistent with it being low spin at 100 K. The Cu(II) 1D chain
      complex has an N4O2 coordination sphere as in this case the "spare" pyridine
      donor out the back of the py-pzpypz ligand bridges to the next Cu(II) center in
      the chain, hence providing both a terdentate site and a monodentate pyridine to
      the next Cu(II) center, and the coordination sphere is completed by weak axial
      coordination by two DMF solvent molecules. The Cu(II) center in the monometallic
      complex has an N3Cl2 square pyramidal coordination sphere. In all cases, the
      noncoordinating, "spare", pyrazine nitrogen atoms are involved in interesting
      intermolecular interactions, including NPz-pi interactions and nonclassical C
      H...NPz hydrogen bonding. The Fe(II) complex is low spin as expected. Two
      polymorphs of the Co(II) complex were obtained, both of which showed gradual spin
      crossover, with a room temperature T1/2. Two reversible redox processes are
      observed for [Co(II)(py-pzpypz)2](BF4)2, with Em(M(I)/M(II)) = -0.63 V and
      Em(M(II)/M(III)) = +0.37 V, and a quasireversible redox process for [Fe(II)(py
      pzpypz)2](BF4)2, with Em(M(II)/M(III)) = +1.26 V, versus 0.01 M AgNO3/Ag in MeCN.
      These potentials are shifted to significantly higher potentials (by ~0.45 V) than
      the literature values for the corresponding Fe(II) and Co(II) complexes of the
      equivalent all-pyridine ligand, consistent with replacement of the two pyridine
      rings by two pyrazine rings significantly stabilizing the lower oxidation states.

PMID- 25970649
TI  - Functional subdivisions of medial parieto-occipital cortex in humans and nonhuman
      primates using resting-state fMRI.
AB  - Based on its diverse and wide-spread patterns of connectivity, primate
      posteromedial cortex (PMC) is well positioned to support roles in several aspects
      of sensory-, cognitive- and motor-related processing. Previous work in both
      humans and non-human primates (NHPs) using resting-state functional MRI (rs-fMRI)
      suggests that a subregion of PMC, the medial parieto-occipital cortex (mPOC), by
      virtue of its intrinsic functional connectivity (FC) with visual cortex, may only
      play a role in higher-order visual processing. Recent neuroanatomical tracer
      studies in NHPs, however, demonstrate that mPOC also has prominent cortico
      cortical connections with several frontoparietal structures involved in movement
      planning and control, a finding consistent with increasing observations of reach-
      and grasp-related activity in the mPOC of both NHPs and humans. To reconcile
      these observations, here we used rs-fMRI data collected from both awake humans
      and anesthetized macaque monkeys to more closely examine and compare
      parcellations of mPOC across species and explore the FC patterns associated with
      these subdivisions. Seed-based and voxel-wise hierarchical cluster analyses
      revealed four broad spatially separated functional boundaries that correspond
      with graded differences in whole-brain FC patterns in each species. The patterns
      of FC observed are consistent with mPOC forming a critical hub of networks
      involved in action planning and control, spatial navigation, and working memory.
      In addition, our comparison between species indicates that while there are
      several similarities, there may be some species-specific differences in
      functional neural organization. These findings and the associated theoretical
      implications are discussed. 

PMID- 25970652
TI  - Comparison of shear bond strength and bonding time of a novel flash-free bonding
      system.
AB  - OBJECTIVE: To evaluate the bonding time, shear bond strength (SBS), and adhesive
      residue index (ARI) of APC(TM) Flash-Free bonding system. MATERIALS AND METHODS:
      Thirty-six extracted human maxillary premolars were randomly divided into three
      groups (12 per group) and used for this in vitro study: group 1, APC Flash-Free
      Adhesive Coated Appliance System; group 2, Clarity ADVANCED Ceramic Bracket
      pasted manually; group 3 (control group), 3M APC PLUS Adhesive prepasted brackets
      bonded with the extruded flash removed. Bonding time was measured using a
      stopwatch. Bond strength was measured using an Instron at a cross-head speed of 1
      mm/min. The ARI was graded on a scale from 1 to 5. Repeated-measures analysis of
      variance and post hoc Tukey tests were used for statistical analysis. RESULTS: It
      took significantly (P < .001) less time to bond in the APC Flash-Free Adhesive
      group (30.7 +/- 3.3 seconds) compared with the control group (41.8 +/- 4.0
      seconds) and the manual group (39.2 +/- 2.8 seconds). The APC Flash-Free Adhesive
      coated bracket had significantly (P < .001) greater SBS (13.7 +/- 2.2 MPa)
      compared with the control group (10.8 +/- 2.0 MPa) and the manual group (10.4 +/-
      1.4 MPa). The ARI was significantly (P < .001) greater with the APC Flash-Free
      Adhesive coated bracket compared with that of the other two groups. CONCLUSIONS:
      Compared with other methods of bonding, the APC Flash-Free Adhesive Coated System
      can potentially reduce bonding time while increasing SBS.

PMID- 25970653
TI  - Implementation and Operational Research: Convenient HIV Testing Service Models
      Are Attracting Previously Untested Gay and Bisexual Men: A Cross-sectional Study.
AB  - INTRODUCTION: HIV testing is a cornerstone of the treatment as prevention
      approach. We assessed which HIV testing service delivery models were more likely
      to attract untested or infrequent tested gay, bisexual and other men who have sex
      with men (GBM). METHODS: We compared demographics, risk behavior, and HIV testing
      history among new GBM clients attending 3 different HIV testing service models
      (fast-track Xpress clinic, fixed-site community-based service, and time-limited
      community-based shopfront) between August 2013 and May 2014. We used bivariate
      and multivariate regression to assess factors (including service model)
      associated with being untested or infrequent testers (not tested within the past
      12 months). RESULTS: Overall, 1704 new GBM attended the services; 19% were
      untested and 41% were infrequent testers. Across the services, there were
      significant differences in demographics, risk behavior, and HIV testing history.
      The overall HIV seropositivity was 1.2% (95% confidence interval: 0.8% to 1.9%)
      and sexually transmitted infection positivity was 12.4% (95% confidence interval:
      11.6 to 17.2) with no significant differences across services. Factors
      independently associated with being untested were attendance at the 2 community
      sites, younger age, being born in Asia, living in North Sydney, being bisexual
      and reporting fewer male sexual partners. Factors independently associated with
      infrequent testers were attending the fast track Xpress clinic, being older,
      being born in Asia, and reporting fewer male partners. CONCLUSIONS: The findings
      suggest both community and fast track testing service models are important to
      increase HIV testing among GBM with a similar yield of HIV diagnoses at the 3
      services. The community models reached more untested men and the fast track model
      more infrequent testers.

PMID- 25970654
TI  - Capacitive Deionization using Biomass-based Microporous Salt-Templated Heteroatom
      Doped Carbons.
AB  - Microporous carbons are an interesting material for electrochemical applications.
      In this study, we evaluate several such carbons without/with N or S doping with
      regard to capacitive deionization. For this purpose, we extent the salt
      templating synthesis towards biomass precursors and S-doped microporous carbons.
      The sample with the largest specific surface area (2830 m(2)  g(-1) ) showed 1.0
      wt % N and exhibited a high salt-sorption capacity of 15.0 mg g(-1) at 1.2 V in 5
      mM aqueous NaCl. While being a promising material from an equilibrium performance
      point of view, our study also gives first insights to practical limitations of
      heteroatom-doped carbon materials. We show that high heteroatom content may be
      associated with a low charge efficiency. The latter is a key parameter for
      capacitive deionization and is defined as the ratio between the amounts of
      removed salt molecules and electrical charge.

PMID- 25970655
TI  - Investigating the mechanical function of the cervix during pregnancy using finite
      element models derived from high-resolution 3D MRI.
AB  - Preterm birth is a strong contributor to perinatal mortality, and preterm infants
      that survive are at risk for long-term morbidities. During most of pregnancy,
      appropriate mechanical function of the cervix is required to maintain the
      developing fetus in utero. Premature cervical softening and subsequent cervical
      shortening are hypothesized to cause preterm birth. Presently, there is a lack of
      understanding of the structural and material factors that influence the
      mechanical function of the cervix during pregnancy. In this study we build finite
      element models of the pregnant uterus, cervix, and fetal membrane based on
      magnetic resonance imagining data in order to examine the mechanical function of
      the cervix under the physiologic loading conditions of pregnancy. We calculate
      the mechanical loading state of the cervix for two pregnant patients: 22 weeks
      gestational age with a normal cervical length and 28 weeks with a short cervix.
      We investigate the influence of (1) anatomical geometry, (2) cervical material
      properties, and (3) fetal membrane material properties, including its adhesion
      properties, on the mechanical loading state of the cervix under physiologically
      relevant intrauterine pressures. Our study demonstrates that membrane-uterus
      interaction, cervical material modeling, and membrane mechanical properties are
      factors that must be deliberately and carefully handled in order to construct a
      high quality mechanical simulation of pregnancy. 

PMID- 25970656
TI  - Tetranorsesquiterpenoids and Santalane-Type Sesquiterpenoids from Illicium
      lanceolatum and Their Antimicrobial Activity against the Oral Pathogen
      Porphyromonas gingivalis.
AB  - The methanol extract of the leaves of Illicium lanceolatum, indigenous to Fujian
      Province, People's Republic of China, was found to exhibit antimicrobial activity
      against the periodontal pathogen Porphyromonas gingivalis, and a bioassay-guided
      fractionation led to the isolation of two new compounds, 1 and 2, along with two
      known santalane-type sesquiterpenoids, 3 and 4. The structures of lanceolactone A
      (1) and lanceolactone B (2) were elucidated by analyzing their 2D NMR
      spectroscopic data. Compounds 1 and 2 were assigned as new
      tetranorsesquiterpenoids with a spiroacetal ring and tricyclic structure,
      respectively. Compound 3 (alpha-santal-11-en-10-one) showed potent antimicrobial
      activity against the oral pathogen P. gingivalis. 

PMID- 25970657
TI  - Pediatric second primary malignancies after retinoblastoma treatment.
AB  - BACKGROUND: Children with retinoblastoma carry a high risk to develop second
      primary malignancies in childhood and adolescence. This study characterizes the
      type of pediatric second primary malignancies after retinoblastoma treatment and
      investigates the impact of different treatment strategies and prognostic factors
      at presentation. PROCEDURE: All national patients treated for retinoblastoma at
      the German referral center with a current age of 6-27 years were invited to
      participate in a study to characterize late effects. RESULTS: Data on pediatric
      second primary malignancies were recorded from 488 patients. Ten developed a
      malignancy before the age of 18 years. For children with heterozygous oncogenic
      RB1 alteration (heritable retinoblastoma), the cumulative incidence to develop a
      second malignancy at the age of 10 years was 5.2% (95% CI 1.7; 8.7%). This
      results in an elevated risk for sarcoma (n = 4) (SIR 147.98; 95% CI 39.81;
      378.87) and leukemia (n = 4) (SIR 41.38; 95% CI 11.13; 105.95). Neither the
      functional type of the RB1 alteration nor its origin showed a significant impact.
      Treatment modality influenced incidence, latency, and type of malignancy.
      Previous radiotherapy increased the risk for solid tumors and 3 of 91 children
      developed acute leukemia after chemotherapy. However, 2 of 10 malignancies were
      diagnosed in patients with heritable retinoblastoma but without previous
      chemotherapy or external beam radiotherapy. CONCLUSIONS: Screening for second
      primary malignancy is an important part of pediatric oncological follow-up in
      patients with heritable retinoblastoma. For patients with sporadic unilateral
      retinoblastoma, genetic information influences treatment decisions and allows
      tailoring of follow-up schedules.

PMID- 25970659
TI  - Movement-Based Behaviors and Leukocyte Telomere Length among US Adults.
AB  - INTRODUCTION: Short leukocyte telomere length (LTL) has become a hallmark
      characteristic of aging. Some, but not all, evidence suggests that physical
      activity (PA) may play an important role in attenuating age-related diseases and
      may provide a protective effect for telomeres. The purpose of this study was to
      examine the association between PA and LTL in a national sample of US adults from
      the National Health and Nutrition Examination Survey. METHODS: National Health
      and Nutrition Examination Survey data from 1999 to 2002 (n = 6503; 20-84 yr) were
      used. Four self-report questions related to movement-based behaviors (MBB) were
      assessed. The four MBB included whether individuals participated in moderate
      intensity PA, vigorous-intensity PA, walking/cycling for transportation, and
      muscle-strengthening activities. An MBB index variable was created by summing the
      number of MBB an individual engaged in (range, 0-4). RESULTS: A clear dose
      response relation was observed between MBB and LTL; across the LTL tertiles,
      respectively, the mean numbers of MBB were 1.18, 1.44, and 1.54 (Ptrend < 0.001).
      After adjustments (including age) and compared with those engaging in 0 MBB,
      those engaging in 1, 2, 3, and 4 MBB, respectively, had a 3% (P = 0.84), 24% (P =
      0.02), 29% (P = 0.04), and 52% (P = 0.004) reduced odds of being in the lowest
      (vs highest) tertile of LTL; MBB was not associated with being in the middle (vs
      highest) tertile of LTL. CONCLUSIONS: Greater engagement in MBB was associated
      with reduced odds of being in the lowest LTL tertile.

PMID- 25970660
TI  - Altered Psychological Responses to Different Magnitudes of Deception during
      Cycling.
AB  - PURPOSE: Deceptive manipulations of performance intensity have previously been
      investigated in cycling time trials (TT) but used different magnitudes, methods,
      and task durations. This study examines previously used magnitudes of deception
      during 16.1-km TT and explores yet unexamined psychological responses. METHODS:
      Twelve trained cyclists completed five TT, performing two baseline trials alone,
      one against a simulated dynamic avatar representing 102% of fastest baseline
      trial (TT(102%)), one against a 105% avatar (TT(105%)), and one against both
      avatars (TT(102%,105%)). RESULTS: Deceptive use of competitors to disguise
      intensity manipulation enabled accomplishment of performance improvements greater
      than their perceived maximal (1.3%-1.7%). Despite a similar improvement in
      performance, during TT(102%,105%), there was significantly lower affect and self
      efficacy to continue pace than those during TT(105%) (P < 0.05), significantly
      lower self-efficacy to compete than that during TT(102%) (P = 0.004), and greater
      RPE than that during TTFBL (P < 0.001). CONCLUSIONS: Because the interpretation
      of performance information and perceptions depends on the manner in which it is
      presented, i.e., "framing effect," it could be suggested that the summative
      effect of two opponents could have evoked negative perceptions despite eliciting
      a similar performance. Magnitudes of deception produce similar performance
      enhancement yet elicit diverse psychological responses mediated by the external
      competitive environment the participants were performing in.

PMID- 25970658
TI  - Conformational landscape and pathway of disulfide bond reduction of human alpha
      defensin.
AB  - Human alpha defensins are a class of antimicrobial peptides with additional
      antiviral activity. Such antimicrobial peptides constitute a major part of
      mammalian innate immunity. Alpha defensins contain six cysteines, which form
      three well defined disulfide bridges under oxidizing conditions. Residues C3-C31,
      C5-C20, and C10-C30 form disulfide pairs in the native structure of the peptide.
      The major tissue in which HD5 is expressed is the crypt of the small intestine,
      an anaerobic niche that should allow for substantial pools of both oxidized and
      (partly) reduced HD5. We used ion mobility coupled to mass spectrometry to track
      the structural changes in HD5 upon disulfide bond reduction. We found evidence of
      stepwise unfolding of HD5 with sequential reduction of the three disulfide bonds.
      Alkylation of free cysteines followed by tandem mass spectrometry of the
      corresponding partially reduced states revealed a dominant pathway of reductive
      unfolding. The majority of HD5 unfolds by initial reduction of C5-C20, followed
      by C10-C30 and C3-C31. We find additional evidence for a minor pathway that
      starts with reduction of C3-C31, followed by C5-C20 and C10-C30. Our results
      provide insight into the pathway and conformational landscape of disulfide bond
      reduction in HD5. 

PMID- 25970661
TI  - Insights into the Mechanisms of Neuromuscular Fatigue in Boys and Men.
AB  - PURPOSE: The aim of the present study was to investigate the role of central and
      peripheral factors in neuromuscular fatigue induced by repeated maximal
      contractions in children and adults. METHODS: Eleven boys (9.9 +/- 1.2 yr) and 12
      men (23.9 +/- 3.5 yr) completed a fatigue protocol consisting in a repetition of
      5-s maximal isometric voluntary contractions (MVC) of the knee extensors
      separated by 5-s passive recovery periods until the generated torque reached 60%
      of its initial value. Single magnetic stimulations were delivered to the femoral
      nerve every five MVC to follow the course of voluntary activation level and the
      amplitude of the potentiated twitch torque (Qtw(pot)) and vastus lateralis and
      rectus femoris concomitant M-waves (Mmax). RESULTS: Torque reached 60% of initial
      value after 49.5 +/- 16.8 and 34.0 +/- 19.6 repetitions in boys and men,
      respectively (P < 0.05). Furthermore, men showed significantly higher knee
      extensor MVC decline than boys between 50% and 90% of total repetitions (P <
      0.05). Voluntary activation remained unchanged in men, whereas it decreased
      significantly in boys (P < 0.05). In contrast, whereas Qtw(pot) remained
      unchanged in boys, Qtw(pot) decreased progressively up to 60% of total
      repetitions in men (P < 0.001). Finally, Mmax remained unchanged for vastus
      lateralis and rectus femoris muscles in both groups. CONCLUSIONS: Children
      experienced no apparent peripheral fatigue and higher central fatigue than
      adults. The greater fatigue resistance in children could be related to a strategy
      of the CNS aimed at limiting the recruitment of motor units to prevent any
      extensive peripheral fatigue.

PMID- 25970662
TI  - Impaired Skeletal Muscle Oxygenation and Exercise Tolerance in Pulmonary
      Hypertension.
AB  - BACKGROUND: Limb muscle dysfunction is documented in pulmonary arterial
      hypertension (PAH), but little is known regarding muscle oxygen (O2) supply and
      its possible effects on exercise tolerance in PAH. METHODS: Ten patients with PAH
      and 10 matched controls underwent progressive maximal cardiopulmonary exercise
      test, voluntary and nonvolitional dominant quadriceps muscle strength measures,
      and nondominant quadriceps biopsy to assess maximal oxygen uptake, muscle
      function, and lower limb fiber type and capillarity, respectively. Both groups
      then performed normoxic and hyperoxic submaximal intensity exercise protocol at
      the same absolute workload during which muscle O2 supply was assessed by
      measuring changes in myoglobin-deoxyhemoglobin level (Delta[Mb-HHb]) and tissue
      oxygenation index in the dominant quadriceps using near-infrared spectroscopy.
      Changes in cardiac output, estimated systemic O2 delivery, and systemic O2
      saturation were also assessed noninvasively throughout both submaximal exercises.
      RESULTS: Patients with PAH displayed lower maximal oxygen uptake (P < 0.01),
      skeletal muscle strength (P < 0.05), and capillarity (P = 0.01). Throughout the
      normoxic submaximal exercise protocol, Delta[Mb-HHb] (P < 0.01) was higher
      whereas changes in tissue oxygenation index (P < 0.01) and systemic O2 saturation
      (P = 0.01) were lower in patients with PAH compared with those in controls.
      Conversely, changes in cardiac output and estimated systemic O2 delivery were
      similar between groups. Muscle oxygenation remained unchanged with O2
      supplementation. Among variables known to influence tissue oxygenation, only
      quadriceps capillarity density correlated with Delta[Mb-HHb] (r = -0.66, P <
      0.01), which in turn correlated with maximal oxygen uptake (r = -0.64, P < 0.01),
      6-min walked distance (r = -0.74, P = 0.01), and both voluntary (r = -0.46, P =
      0.04) and nonvolitional (r = -0.50, P = 0.02) quadriceps strength. CONCLUSIONS:
      Capillary rarefaction within the skeletal muscle influences exercise tolerance
      and quadriceps strength at least partly through impaired muscle oxygen supply in
      PAH.

PMID- 25970663
TI  - Longitudinal Increases in Knee Abduction Moments in Females during Adolescent
      Growth.
AB  - PURPOSE: Knee abduction moment (KAM) is an injury risk factor for anterior
      cruciate ligament (ACL) injury that shows divergent incidence between males and
      females during adolescence. The objective of this study was to determine the
      relation between skeletal growth and increased KAM. The hypotheses tested were
      that females would demonstrate peak KAM during landing at peak height velocity
      (PHV) and that they would diverge from males at PHV. METHODS: The subject pool
      consisted of 674 females and 218 males (1387 female and 376 male assessments) who
      participated in a preseason testing session before their basketball or soccer
      seasons. They were tested longitudinally for multiple years (2 +/- 1 yr) to
      capture maturation via estimates of percent (%) adult stature and biomechanical
      analysis during a drop vertical jump maneuver. Data were analyzed using three
      dimensional motion analysis that used a 37 retroreflective marker body model and
      inverse dynamics to calculate segment joint centers and peak KAM. RESULTS: Mature
      females, as defined as 92% adult stature or greater, displayed increased peak KAM
      and knee abduction angles relative to growing (<=91% adult stature) adolescent
      females (P < 0.001). A significant sex-maturation (% adult stature) interaction
      (P < 0.001) in peak KAM was observed. Post hoc analyses showed consistent sex
      differences in groups greater than or equal to, but not less than, 92% adult
      stature, which is approximately at PHV. Hence, sex differences in peak KAM and
      PHV coincide. CONCLUSIONS: Increases in peak KAM during and after PHV seem to
      coincide with increased risk of ACL injury in females. KAM peaked in females at
      PHV. Tracking longitudinal increases in peak KAM may be useful for the
      identification of females at increased risk of ACL injury.

PMID- 25970664
TI  - The Prospective Association between Different Types of Exercise and Body
      Composition.
AB  - PURPOSE: Despite the widely accepted benefits of exercise on chronic disease
      risk, controversy remains on the role of exercise in weight loss. This study
      examined the effect of different exercise types on measures of adiposity across
      different fat categories. METHODS: A total of 348 young adults (49% male; 28 +/-
      4 yr), participating in an ongoing observational study provided valid data over a
      period of 12 months. Fat mass (FM) and lean mass (LM) were measured via dual x
      ray absorptiometry every 3 months. Percent body fat was calculated and used to
      differentiate between normal-fat, "overfat," and obese participants. At each
      measurement time point, participants reported engagement (min.wk) in aerobic
      exercise, resistance exercise, and other forms of exercise. RESULTS: Most
      participants (93%) reported some exercise participation during the observation
      period. Total exercise or specific exercise types did not significantly affect
      subsequent body mass index after adjusting for sex, ethnicity, age, and baseline
      values of adiposity and exercise. Resistance exercise affected LM (P < 0.01) and
      FM (P < 0.01), whereas aerobic exercise only affected FM (P < 0.01). Any exercise
      type positively affected LM in normal-fat participants (P < 0.04). In overfat and
      obese participants, FM was reduced with increasing resistance exercise (P <=
      0.02) but not with aerobic exercise (P >= 0.09). Additionally adjusting for
      objectively assessed total physical activity level did not change these results.
      CONCLUSIONS: Despite the limited effects on body mass index, exercise was
      associated with beneficial changes in body composition. Exercise increased LM in
      normal-fat participants and reduced FM in overfat and obese adults. Adults with
      excess body fat may benefit particularly from resistance exercise.

PMID- 25970665
TI  - No Effects of a Short-Term Gluten-free Diet on Performance in Nonceliac Athletes.
AB  - PURPOSE: Implementation of gluten-free diets among nonceliac athletes has rapidly
      increased in recent years because of perceived ergogenic and health benefits. The
      aim of this study was to investigate the effects of a gluten-free diet (GFD) on
      exercise performance, gastrointestinal (GI) symptoms, perceived well-being,
      intestinal injury, and inflammatory responses in nonceliac athletes. METHODS:
      Thirteen competitive endurance cyclists (8 males, 5 females) with no positive
      clinical screening for celiac disease or history of irritable bowel syndrome
      (mean +/- SD; age, 32 +/- 7 yr; weight, 71.1 +/- 13.4 kg; height, 177.0 +/- 11.8
      cm, VO2max 59.1 +/- 8.0 mL.kg-1.min-1) were allocated to a 7-d gluten-containing
      diet (GCD) or GFD separated by a 10-d washout in a controlled, randomized, double
      blind, crossover study. Cyclists ate a GFD alongside either gluten-containing or
      gluten-free food bars (16 g wheat gluten per day) while habitual training and
      nutrition behaviors were controlled. During each diet, cyclists completed the
      Daily Analysis of Life Demand for Athletes (DALDA) and GI questionnaires
      (postexercise and daily). On day 7, cyclists completed a submaximal steady-state
      (SS) 45-min ride at 70% Wmax followed by a 15-min time trial (TT). Blood samples
      were taken preexercise, post-SS, and post-TT to determine intestinal fatty acid
      binding protein (IFABP) and inflammatory markers (cytokine responses: interleukin
      [IL] 1beta, IL-6, IL-8, IL-10, IL-15, tumor necrosis factor alpha). Mixed effects
      logistic regression was used to analyze data. RESULTS: TT performance was not
      significantly different (P = 0.37) between the GCD (245.4 +/- 53.4 kJ) and GFD
      (245.0 +/- 54.6 kJ). GI symptoms during exercise, daily, and DALDA responses were
      similar for each diet (P > 0.11). There were no significant differences in IFABP
      (P = 0.69) or cytokine (P > 0.13) responses. CONCLUSIONS: A short-term GFD had no
      overall effect on performance, GI symptoms, well-being, and a select indicator of
      intestinal injury or inflammatory markers in nonceliac endurance athletes.

PMID- 25970666
TI  - Light Physical Activity Is Associated with Quality of Life after Colorectal
      Cancer.
AB  - PURPOSE: Emerging evidence suggests that light physical activity (LPA), besides
      moderate-to-vigorous physical activity (MVPA), may beneficially influence
      physical functioning of colorectal cancer survivors, but its relation with other
      health-related outcomes is unknown. We applied a biopsychosocial approach to
      investigate independent associations between self-reported LPA, MVPA, and
      multiple health-related quality of life (HRQoL) outcomes in 2- to 10-yr
      postdiagnosis colorectal cancer survivors. METHODS: Stage I-III colorectal cancer
      survivors diagnosed between 2002 and 2010 at Maastricht University Medical
      Center+, the Netherlands, were included in a cross-sectional study (n = 151).
      Time spent in LPA and MVPA (h.wk-1), and HRQoL outcome scores (0-100 points) were
      assessed by validated questionnaires. RESULTS: Median time spent in LPA and MVPA
      was 10.0 (interquartile range, 2.0-22.0) and 8.7 h.wk-1 (4.5-15.0), respectively.
      In multivariable linear regression models, both LPA and MVPA were significantly
      and independently associated with higher physical functioning (mean difference
      [MD] between highest and lowest quartile, 10.2; 95% confidence interval [CI], 0.2
      20.3; and 14.5; 5.1-23.9, respectively; both P-trend < 0.05). In addition, LPA
      was significantly associated with higher role functioning (MD, 19.5; 95% CI, 6.9
      32.1; P-trend < 0.01) and lower disability (MD, -9.9; 95% CI, -17.8 to -1.9; P
      trend = 0.02), independent from MVPA. Subgroup analyses showed that beneficial
      associations between LPA and HRQoL were mainly observed in women and participants
      with multiple comorbidities. CONCLUSIONS: Self-reported LPA, besides MVPA, was
      beneficially associated with multiple HRQoL outcomes in colorectal cancer
      survivors, especially in women and survivors with multiple comorbidities.
      Prospective studies are warranted to establish whether LPA is a suitable target
      for personalized lifestyle interventions to improve the HRQoL of colorectal
      cancer survivors.

PMID- 25970667
TI  - Effects of a Physical Activity Intervention in Preschool Children.
AB  - PURPOSE: This study aimed to evaluate a multicomponent, child-appropriate
      preschool intervention program led by preschool teachers to enhance physical
      activity (PA) and motor skill performance (MS) in 4- and 5-yr-old children.
      METHODS: Evaluation involved 709 children (mean age, 4.7 +/- 0.6 yr; 49.5% girls)
      from 41 preschools (intervention group, n = 21; control group, n = 20) in the
      rural and urban surroundings of two German cities. Children in the intervention
      group received a daily PA intervention lasting 30 min and PA homework over one
      academic year, which was designed by professionals but led by preschool teachers.
      The intervention included educational components for parents and teachers.
      Primary outcomes were MS (composite MS score) and objectively measured moderate
      to-vigorous PA (MVPA) by accelerometry. Measurements were performed at baseline,
      midintervention, and postintervention as well as 2-4 months after the end of
      intervention. Intervention effects were analyzed by repeated measurement analysis
      adjusted for group, sex, age, baseline outcomes, urban/rural location of the
      preschool, and cluster (preschool). RESULTS: Compared with controls, children in
      the intervention group showed positive effects in MS at postintervention
      (estimate effect, 0.625 z-score points; 95% confidence interval (CI), 0.276
      0.975; P = 0.001) and at follow-up (estimate effect, 0.590 z-score points; 95%
      CI, 0.109-1.011; P = 0.007) and an increase in MVPA from baseline to
      postintervention by 0.5% of total wearing time (95% CI, 0.002%-1.01%; P = 0.049)
      at borderline significance. There was no benefit on MVPA for the intervention
      group between baseline and follow-up. CONCLUSIONS: A child-appropriate,
      multidimensional PA intervention could sustainably improve MS but not PA.
      Findings suggest that a change in health-related behaviors is difficult. Future
      research should implement participatory intervention components in preschool
      setting and better integrate the families of the children.

PMID- 25970668
TI  - Effect of Breakfast Omission on Energy Intake and Evening Exercise Performance.
AB  - INTRODUCTION: Breakfast omission may reduce daily energy intake. Exercising
      fasted impairs performance compared with exercising after breakfast, but the
      effect breakfast omission has on evening exercise performance is unknown. This
      study assessed the effect of omitting breakfast on evening exercise performance
      and within-day energy intake. METHODS: Ten male, habitual breakfast eaters
      completed two trials in a randomized, counterbalanced order. Subjects arrived at
      the laboratory in an overnight-fasted state and either consumed or omitted a 733
      +/- 46 kcal (3095 +/- 195 kJ) breakfast. Ad libitum energy intake was assessed at
      4.5 h (lunch) and 11 h (dinner). At 9 h, subjects completed a 30-min cycling
      exercise at approximately 60% VO2peak, followed by a 30-min maximal cycling
      performance test. Food was not permitted for subjects once they left the
      laboratory after dinner until 0800 h the following morning. Acylated ghrelin, GLP
      1(7-36), glucose, and insulin were assessed at 0, 4.5, and 9 h. Subjective
      appetite sensations were recorded throughout. RESULTS: Energy intake was 199 +/-
      151 kcal greater at lunch (P < 0.01) after breakfast omission compared with that
      after breakfast consumption and tended to be greater at dinner after consuming
      breakfast (P = 0.052). Consequently, total ad libitum energy intake was similar
      between trials (P = 0.196), with 24-h energy intake 19% +/- 5% greater after
      consuming breakfast (P < 0.001). Total work completed during the exercise
      performance test was 4.5% greater after breakfast (314 +/- 53 vs 300 +/- 56 kJ; P
      < 0.05). Insulin was greater during breakfast consumption at 4.5 h (P < 0.05),
      with no other interaction effect for hormone concentrations. CONCLUSIONS:
      Breakfast omission might be an effective means of reducing daily energy intake
      but may impair performance later that day, even after consuming lunch.

PMID- 25970669
TI  - [Performance enhancement by carbohydrate intake during sport: effects of
      carbohydrates during and after high-intensity exercise].
AB  - Endogenous carbohydrate availability does not provide sufficient energy for
      prolonged moderate to high-intensity exercise. Carbohydrate ingestion during high
      intensity exercise can therefore enhance performance.- For exercise lasting 1 to
      2.5 hours, athletes are advised to ingest 30-60 g of carbohydrates per hour.-
      Well-trained endurance athletes competing for longer than 2.5 hours at high
      intensity can metabolise up to 90 g of carbohydrates per hour, provided that a
      mixture of glucose and fructose is ingested.- Athletes participating in
      intermittent or team sports are advised to follow the same strategies but the
      timing of carbohydrate intake depends on the type of sport.- If top performance
      is required again within 24 hours after strenuous exercise, the advice is to
      supplement endogenous carbohydrate supplies quickly within the first few hours
      post-exercise by ingesting large amounts of carbohydrate (1.2 g/kg/h) or a lower
      amount of carbohydrate (0.8 g/kg/h) with a small amount of protein (0.2-0.4
      g/kg/h).

PMID- 25970670
TI  - [Worldwide access to surgery: a necessity, not a luxury].
AB  - Many people in developing countries lack access to basic surgical care. This lack
      of access leads to preventable mortality and disability. Mortality due to
      surgically treatable conditions currently exceeds that due to HIV, TB and malaria
      combined. However, efforts by global healthcare organisations to address this
      problem remain limited. Essential surgery consist of basic surgical interventions
      that can save lives and prevent disability. It involves a limited number of
      interventions, is cost-effective and can be implemented sustainably in national
      healthcare systems. Essential surgery should therefore be accessible to everyone
      worldwide. In this article we discuss why it has received insufficient attention
      as a component of global healthcare. We also look at initiatives that aim to
      change this status quo. 

PMID- 25970671
TI  - [A woman with increasing pain after cholecystectomy].
AB  - A 25-year-old female presented with abdominal pain and collapse 3 days after a
      laparoscopic cholecystectomy. The MRCP images suggested a leakage from the stump
      of the cystic duct. However, an ERCP showed a leakage of a subvesical bile duct
      arriving from the left hepatic duct. Diagnostic and treatment modalities are
      discussed.

PMID- 25970672
TI  - [An unexpected pathology report of a sentinel lymph node].
AB  - A 60-year-old woman was treated for breast carcinoma. She underwent a total
      mastectomy with sentinel node biopsy of her right breast. Pathologic examination
      of the sentinel lymph node showed an unusual large nodal naevus. 

PMID- 25970674
TI  - [The use of medical journals by medical students. Which medical journals are
      read?].
AB  - OBJECTIVE: To investigate the role of scientific medical journals in Dutch
      medical curricula. DESIGN: Descriptive questionnaire study. METHOD: In 2013,
      medical students (from year 3 onwards) at the Leiden University Medical Centre
      (LUMC), were invited to respond to an online questionnaire. They were presented
      with 28 multiple-choice questions and 11 statements about the use of scientific
      medical journals in the medical curriculum. We calculated the frequencies of the
      answers per question and analysed differences between medical students using two
      by-two tables. RESULTS: The questionnaire was completed by 680 (53.0%) of 1277
      invited medical students enrolled at the LUMC. Most of the respondents were those
      doing clinical rotations (56.6%) and 60.1% had research experience. More than
      half of the students read at least one scientific journal a few times per month;
      this percentage was 38.8% among third-year students, 49.3% among fourth-year
      students, 60.0% among those on clinical rotation, and was higher among students
      with research experience (63.3%) than among those without research experience
      (44.1%). Nearly 90% of students agreed with the statement that the development of
      academic and scientific education should take place in the bachelor's phase of
      medical school. CONCLUSION: Medical students start to read scientific medical
      journals at an early phase in the medical curriculum and this increases further
      when students start to undertake research projects or go on clinical rotation.
      Medical curricula should be constructed in such a way that medical students learn
      to select and interpret research findings adequately for themselves before they
      turn to articles from scientific medical journals.

PMID- 25970676
TI  - [Cost-effectiveness research in elderly residents in long-term care: prevention
      is better than cure, but not always cheaper].
AB  - Cost-effectiveness research in elderly residents in long-term care facilities is
      based on general principals of cost-effectiveness research; these have been
      developed primarily from the perspective of relatively healthy adults in curative
      medicine. These principals are, however, inadequate when evaluating interventions
      for the fragile elderly in long-term care, both in terms of the value attached to
      the health of patients and to the specific decision-making context of the
      institution. Here we discuss the pitfalls of cost-effectiveness research in long
      term care facilities, illustrated by two prevention interventions for prevalent
      conditions in nursing homes: pressure ulcers and urinary tract infections. These
      turned out to be effective, but not cost-effective. 

PMID- 25970677
TI  - [Sir Geoffrey Marshall, anaesthetist before the term existed].
AB  - At the start of World War I, relatively inexperienced physicians were responsible
      for administering anaesthesia to severely injured soldiers in shock. Lack of
      knowledge, experience and proper equipment led to high mortality rates. Based on
      his pre-war experience in the department of respiratory physiology at Guy's
      Hospital in London, the British physician Geoffrey Marshall was ordered to
      investigate the high mortality rates. He was one of the first physicians to
      systematically record blood pressure, heart rate and haemoglobin level. The
      anaesthetic techniques of the time resulted in deep hypotension and high
      mortality. Marshall's main achievement was his design of a machine which could be
      used to reliably administer a mixture of ether, oxygen and nitrous oxide. This
      led to much more stable anaesthesia and a substantial decrease in mortality.
      After World War I, his invention became known as Boyle's machine, providing a
      template for all subsequent anaesthetic machines. 

PMID- 25970678
TI  - [Does it still make sense? Deprescribing in the frail elderly].
AB  - Elderly patients with multimorbidity often take several chronically used
      medicines. A large part of this polypharmacy is preventive in intention. Although
      one would expect that, at the end of life, the ratio of preventive therapy, would
      decrease in proportion to symptomatic treatment, this appears often not to be the
      case in practice. Although patients seem to be open to stopping medication,
      physicians seem to find it difficult to deprescribe preventive medication in
      particular. One of the major reasons for this is uncertainty about the potential
      clinical consequences of deprescribing. Since frail elderly people seldom
      participate in clinical drug trials, clear information is not available for this
      patient group on the balance between the chance of efficacy and the risk of harm
      of drug therapy. Discussion with the patient about his or her preferences and
      options with respect to drug therapy is the basis for all subsequent steps and
      must form part of the periodic reviews of medication.

PMID- 25970679
TI  - [Limits to euthanasia].
AB  - A recent survey showed that less than half of Dutch physicians would find it
      conceivable to grant a request for euthanasia from a patient suffering from
      psychiatric disease or dementia, or who is tired of life. Because of a broader
      interpretation by the Regional Review Committees of the official criteria for due
      care, all recent cases of euthanasia in these specific groups of patients had
      been accepted. In this commentary it is argued that, following recent social
      developments in the Netherlands (including cuts in provision of care for the
      elderly and of mental health care, and a narrowed view about end-of-life issues),
      the official euthanasia criteria for due care are no longer suitable if we are to
      avoid a 'slippery slope' effect in cases such as those mentioned above. The
      criteria of a) a voluntary and well-considered request and b) absence of
      reasonable treatment alternatives are particularly under pressure. A plea is hold
      for a return to stricter interpretation of the criteria. 

PMID- 25970680
TI  - [New recommendations for the Dutch neonatal screening programme. A report from
      the Health Council of the Netherlands].
AB  - The Health Council of the Netherlands recently issued a report advising adding 14
      new disorders to the current neonatal screening programme: 11 metabolic
      conditions, severe combined immunodeficiency disease, beta-thalassaemia major and
      HbH disease. This recommendation was made because of the availability of new
      tests and treatments. The new criteria of availability and accessibility of
      treatment became relevant following discussions on reimbursement of enzyme
      replacement therapy for Pompe's disease. The potential for alternative or
      complementary measures for prevention are discussed, such as preconception and
      prenatal carrier screening. This report advises against reporting carrier
      information following newborn screening: advice that is not in line with earlier
      Health Council advice. A further recommendation is that newborn screening for
      untreatable conditions is not indicated now. Screening for untreatable conditions
      may not be the responsibility of national public health agencies, but alternative
      stakeholders have not been considered in the report. 

PMID- 25970681
TI  - Genetic Diversity of the Invasive Gall Wasp Leptocybe invasa (Hymenoptera:
      Eulophidae) and of its Rickettsia Endosymbiont, and Associated Sex-Ratio
      Differences.
AB  - The blue-gum chalcid Leptocybe invasa Fisher & LaSalle (Hymenoptera: Eulophidae)
      is a gall wasp pest of Eucalyptus species, likely native to Australia. Over the
      past 15 years it has invaded 39 countries on all continents where eucalypts are
      grown. The worldwide invasion of the blue gum chalcid was attributed to a single
      thelytokous morphospecies formally described in 2004. Subsequently, however,
      males have been recorded in several countries and the sex ratio of field
      populations has been found to be highly variable in different areas. In order to
      find an explanation for such sex ratio differences, populations of L. invasa from
      a broad geographical area were screened for the symbionts currently known as
      reproductive manipulators, and both wasps and symbionts were genetically
      characterized using multiple genes. Molecular analyses suggested that L. invasa
      is in fact a complex of two cryptic species involved in the rapid and efficient
      spread of the wasp, the first recovered from the Mediterranean region and South
      America, the latter from China. All screened specimens were infected by
      endosymbiotic bacteria belonging to the genus Rickettsia. Two closely related
      Rickettsia strains were found, each infecting one of the two putative cryptic
      species of L. invasa and associated with different average sex ratios. Rickettsia
      were found to be localized in the female reproductive tissues and transovarially
      transmitted, suggesting a possible role of Rickettsia as the causal agent of
      thelytokous parthenogenesis in L. invasa. Implications for the variation of sex
      ratio and for the management of L. invasa are discussed. 

PMID- 25970682
TI  - Clear cell-papillary renal cell carcinoma of the kidney not associated with end
      stage renal disease: clinicopathologic correlation with expanded immunophenotypic
      and molecular characterization of a large cohort with emphasis on relationship
      with renal angiomyoadenomatous tumor.
AB  - Clear cell-papillary renal cell carcinoma (CC-Pap RCC) is a recently described
      renal tumor initially reported in the setting of end-stage renal disease (ESRD).
      It has unique morphologic and immunohistochemical features that differentiate it
      from the more common clear cell RCC and papillary RCC. Recently, these tumors
      have also been described in a sporadic setting. We studied 64 cases of CC-Pap RCC
      not associated with ESRD (57 CC-Pap RCCs and 7 cases with features of renal
      angiomyoadenomatous tumors [RAT] including 5 initially diagnosed as such). The
      morphologic features of all cases and the immunohistochemical profile of 59 cases
      were studied along with the clinical and molecular features of 30 and 12 cases,
      respectively. All the tumors were well circumscribed with a mean tumor size of
      2.6 cm and showed a wide array of architectural patterns, usually mixed,
      including tubular (77%), papillary (62%), tubulocystic (52%), and compact nested
      (21%). Seventy-three percent of the cases showed areas in which the tumor nuclei
      had a distinct orientation away from the basement membrane. Ninety-two percent of
      the cases had a low Fuhrman nuclear grade (nuclear grade 2%-86%, and nuclear
      grade 1%-6%); however, 8% cases showed foci of Fuhrman nuclear grade 3. In 4
      cases, epithelial tumor comprised <5% of the tumor; >95% of the tumor was cystic
      or hyalinized. The stroma varied from being minimal to occasionally prominent
      myxoid to hyalinized and rarely with organized amianthoid fibers or well-defined
      smooth muscle bundles. Pathologic stage was reliably assigned in 60 cases, of
      which 93.3% (56 cases) were pT1, 3.3% (2 cases) were pT2, and 3.3% (2 cases) were
      pT3a with extension into the perinephric fat. One case had coagulative necrosis;
      sarcomatoid change and vascular invasion was not identified. The tumors showed a
      fairly typical immunoprofile characterized by positivity for CK7 (100%), HMCK
      (96%), CAIX (94%), and vimentin (100%) with negativity for AMACR, RCC, and TFE3;
      CD10 was positive in 24%. None of the cases tested showed recurrent chromosomal
      imbalances by virtual karyotyping, fluorescence in situ hybridization, or 3p loss
      of heterozygosity analysis. VHL gene mutations were, however, noted in 3 cases (2
      in exon 1 and 1 in exon 3). Clinical follow-up information was available in 47%
      of the patients, with a mean and median follow-up of 47 and 37 months,
      respectively (range, 18 to 108 mo). One case occurred in the setting of VHL
      syndrome and multiple benign cysts. None of the cases showed local recurrence,
      metastasis, or death due to disease. Morphology, immunophenotype, and molecular
      studies did not vary between typical cases, those with prominent smooth muscle
      (so-called RAT), and historically published data on cases occurring in ESRD. Our
      analysis confirms that CC-Pap RCC is a unique subtype of adult renal epithelial
      neoplasia in which tumors are frequently small, are of low nuclear grade and
      pathologic stage, and have extremely favorable short to intermediate range
      prognosis. Tumors occurring sporadically, with prominent smooth muscle stroma (so
      called RAT), and occurring in ESRD are in the spectrum of the same category of
      tumors. 

PMID- 25970683
TI  - Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor:
      two variants of a morphologic, immunohistochemical, and genetic distinct entity
      of renal cell carcinoma.
AB  - Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous
      tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary
      RCC (pRCC). It is a matter of controversy whether their morphologic,
      immunophenotypic, and molecular features allow the definition of a separate renal
      carcinoma entity. The aim of our project was to investigate specific renal
      immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway
      and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT.
      We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25
      markers. VHL gene mutations and allele losses were investigated by Sanger
      sequencing and fluorescence in situ hybridization. Clinical follow-up data were
      obtained for a subset of the patients. No tumor recurrence or tumor-related death
      was observed in any of the patients. Immunohistochemistry and molecular analyses
      led to the reclassification of 3 tumors as ccRCC and TFE3 translocation
      carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very
      similar but not identical, differing from both ccRCC and pRCC. Especially, the
      parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared
      with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7
      (14%) ccpRCC and RAT samples, respectively. Fluorescence in situ hybridization
      analysis disclosed a 3p loss in 2/20 (10%) ccpRCC samples. ccpRCC and RAT have a
      specific morphologic and immunohistochemical profile, but they share similarities
      with the more aggressive renal tumors. On the basis of our results, we regard
      ccpRCC/RAT as a distinct entity of RCCs. 

PMID- 25970684
TI  - Loss of B-cell receptor expression defines a subset of diffuse large B-cell
      lymphoma characterized by silent BCR/PI3K/AKT signaling and a germinal center
      phenotype displaying low-risk clinicopathologic features.
AB  - B-cell receptor (BCR) signaling is crucial for the survival of normal and
      neoplastic B cells, and inhibitors targeting BCR signaling pathways have shown
      promising therapeutic outcomes for patients with B-cell lymphomas. In the current
      study, we analyzed de novo diffuse large B-cell lymphoma without BCR expression
      (DLBCL, BCR) in 25 cases to determine the BCR/phosphatidylinositol-3-kinase/AKT
      (BCR/PI3K/AKT) signaling status, clinicopathologic features, and underlying
      causes leading to the loss of BCR. On the basis of clinical features, 15 (60%)
      DLBCL, BCR patients were classified into the low-risk group, and 18 (86%)
      experienced complete remission. Morphologically and immunophenotypically, DLBCL,
      BCR demonstrated centroblastic cytology (21/25, 84%) and germinal center B-cell
      like cell origin (18/25, 72%). Other components in BCR complexity remained
      intact, on the basis of immunohistochemical findings. Epstein-Barr virus
      infection, deficiency in B-lineage transcription factors (PAX5, Oct-2, and
      Bob.1), and oncogene rearrangement did not seem to be associated with BCR loss.
      The activated form of signaling proteins (pSYK and pAKT) involved in the
      BCR/PI3K/AKT pathway were expressed at low levels in DLBCL, BCR tissue. In vitro
      validation revealed that in DLBCL, BCR cell lines, the BCR/PI3K/AKT pathway did
      not respond to BCR stimulation or inhibition. Our findings suggest that DLBCL,
      BCR was characterized by a silent BCR/PI3K/AKT pathway, germinal center
      phenotype, and low risk and may not be a candidate for BCR-targeted therapies. 

PMID- 25970685
TI  - Pulmonary adenocarcinoma in situ: analyses of a large series with reference to
      smoking, driver mutations, and receptor tyrosine kinase pathway activation.
AB  - Lung adenocarcinomas in situ (AISs) often occur in individuals who have never
      smoked, although smoking is one of the main causes of lung cancer. To
      characterize AIS and, in particular, determine how AIS might be related to
      smoking, we collected a large number of AIS cases and examined clinicopathologic
      features, EGFR and KRAS mutation status, and activation status of receptor
      tyrosine kinase downstream signal pathways, including pAkt, pERK, and pStat3,
      using immunohistochemistry. We identified 110 AISs (36 smokers and 74 nonsmokers)
      among 1549 adenocarcinomas resected surgically during 1995 to 2010. Between the
      AIS of smokers and nonsmokers, only the sex ratio was significantly different;
      all the other clinicopathologic factors including TTF-1 and driver mutations were
      not significantly different: EGFR and KRAS mutation rates (smokers:nonsmokers)
      were 61:58 (%) (P=0.7) and 6.1:1.4 (%) (P=0.2), respectively, whereas, in
      invasive adenocarcinomas, the rates were 41:69 (%) (P<0.001) and 9.4:2.3 (%)
      (P<0.04), respectively. For pAkt and pERK, around 40% to 50% of AISs were
      positive, and for pStat3, >80% were positive, with no significant differences
      between smokers and nonsmokers with AIS. Mucinous AIS (n=8) rarely harbored KRAS
      mutations and expressed significantly less pStat3 (P<0.001) than nonmucinous AIS.
      Taken together, AIS occurs predominantly in female individuals and nonsmokers.
      However, characteristics of AIS arising in smokers and nonsmokers were similar in
      terms of cell lineage, driver mutations, and receptor tyrosine kinase pathway
      activation. Our results suggest that smoking is not a major cause of AIS. Rather,
      smoking may play a role in progression of AIS to invasive adenocarcinoma with AIS
      features. 

PMID- 25970686
TI  - KIT, PDGFRA, and BRAF mutational spectrum impacts on the natural history of
      imatinib-naive localized GIST: a population-based study.
AB  - The mutation status of KIT or PDGFRA notoriously affects the response of advanced
      gastrointestinal stromal tumors (GISTs) to tyrosine kinase inhibitors.
      Conversely, it is currently still unclear whether mutation status impinges on the
      prognosis of localized, untreated GISTs. Hence, at present, this variable is not
      included in decision making for adjuvant therapy. A series of 451 primary
      localized GISTs were analyzed for KIT, PDGFRA, and BRAF mutations. Univariable
      and multivariable analyses and a backward selection procedure were used to assess
      the impact of mutation status on overall survival and to identify prognostically
      homogenous groups. Mutation was a significant prognostic indicator of overall
      survival in naive, localized GISTs (P<0.001): KIT-mutated patients had a worse
      outcome than PDGFRA-mutated or triple-negative (KIT, PDGFRA, BRAF wild-type)
      cases. Multivariable Cox regression models allowed us to identify 3 molecular
      risk groups: group I exhibited the best outcome and included PDGFRA exon 12,
      BRAF, and KIT exon 13-mutated cases; group II, of intermediate clinical phenotype
      (HR=3.06), included triple-negative, KIT exon 17, PDGFRA exon 18 D842V, and
      PDGFRA exon 14-mutated cases; group III displayed the worst outcome (hazard
      ratio=4.52), and comprised KIT exon 9 and exon 11 and PDGFRA exon 18 mutations
      apart from D842V. This study highlights the prognostic impact of mutation status
      on the natural course of GIST and suggests that the molecular prognostic grouping
      may complement the conventional clinicopathologic risk stratification criteria in
      decision making for adjuvant therapy. 

PMID- 25970688
TI  - One hundred thirteen consecutive transgastric liver biopsies for hepatic
      parenchymal diseases: a single-institution study.
AB  - The transgastric approach is a novel method for obtaining liver biopsies in
      patients undergoing upper gastrointestinal endosonography. Avoidance of vascular
      puncture and ability to acquire tissue in patients with obesity or ascites offers
      a practice niche for this technique. Although several series have reported on
      specimen adequacy, biopsy core length, and number of portal tracts, none has
      addressed the diagnostic challenges presented by the fragmented nature of these
      specimens. We systematically evaluated 113 transgastric liver biopsies obtained
      for diagnosis of parenchymal liver disease by 3 needle types and compared them
      with 100 percutaneous and 100 transjugular liver biopsies, respectively.
      Parameters recorded were number of tissue cores, sizes of longest and shortest
      cores, numbers of complete and incomplete portal tracts, morphologic
      characteristics, and adequacy of specimen for diagnosis and staging. In contrast
      to percutaneous and transjugular liver biopsies, transgastric biopsies often
      contained >10 tissue fragments and smaller tissue cores. In addition, 2 of the 3
      types of transgastric needles obtained less numbers of complete portal tracts.
      Transjugular biopsies were also smaller and contained less number of complete
      portal tracts than percutaneous specimens but, unlike transgastric biopsies, only
      rarely contained >10 tissue fragments. Specimen adequacy for diagnosis and
      staging was 80%, 100%, and 98% for transgastric, percutaneous, and transjugular
      biopsies, respectively. Difference in specimen adequacy is related to tissue
      fragmentation of transgastric liver biopsies rather than biopsy core length or
      numbers of complete portal tracts. Tissue fragmentation is particularly
      challenging for staging chronic liver disease. 

PMID- 25970687
TI  - Prognostic factors in myoepithelial carcinoma of salivary glands: a
      clinicopathologic study of 48 cases.
AB  - Myoepithelial carcinoma (MECA) is an underrecognized rare tumor with a diverse
      clinical behavior. The histologic features of this tumor are not well
      characterized, much less its grading, which is controversial. The objective of
      this study is to provide a better characterization of MECA and its prognostic
      factors. A total of 48 cases were retrieved from the pathology files. The cases
      were subjected to a detailed histopathologic, immunohistochemical, statistical,
      and clinical analysis. Tumors were classified as de novo MECA in 22 cases (46%)
      and carcinoma ex-pleomorphic adenoma (CA ex-PA) in 26 cases (54%). Tumor
      necrosis, high mitotic count (>=6/10 high-power fields), and severe pleomorphism
      were identified in 38%, 33%, and 21%, respectively. Perineural invasion, vascular
      invasion, and positive margins were noted in 10%, 12%, and 47%, respectively.
      Median follow-up was 38 months. Four patients had lymph node metastasis at
      presentation, 9 developed local recurrences, and 12 had distant metastases with
      the lung being the most common site (83%). The presence of CA ex-PA, necrosis,
      and vascular invasion correlated significantly with disease-free survival
      (P=0.02, 0.01, 0.03, respectively). No distant recurrence was noted in all 23
      patients lacking necrosis in their neoplasms (median follow-up: 44 mo). MECA is a
      relatively aggressive tumor that is associated with a high rate of distant
      metastasis (27%). Compared with de novo MECA, CA ex-PA correlates with worse
      clinical outcome. A grading system based on the presence of tumor necrosis should
      be used to identify high-grade MECA and predict its clinical behavior. 

PMID- 25970689
TI  - Comments on Carter et al's "activating GNAS mutations in parosteal osteosarcoma".

PMID- 25970690
TI  - CuS@mSiO2-PEG core-shell nanoparticles as a NIR light responsive drug delivery
      nanoplatform for efficient chemo-photothermal therapy.
AB  - We report a facile and low-cost approach to design a difunctional nanoplatform
      (CuS@mSiO2-PEG) as a near-infrared (NIR) light responsive drug delivery system
      for efficient chemo-photothermal therapy. The nanoplatform demonstrated good
      biocompatibility and colloidal stability, as well as high loading capacity for
      the anticancer drug (26.5 wt% for doxorubicin (DOX)). The CuS nanocrystals (core)
      within these CuS@mSiO2-PEG core-shell nanoparticles can effectively absorb and
      convert NIR light to fatal heat under NIR light irradiation for photothermal
      therapy, and the release of DOX from the mesoporous silica (shell) can be
      triggered by pH and NIR light for chemotherapy. When the CuS@mSiO2-PEG/DOX
      nanocomposites were irradiated by 980 nm light, both chemotherapy and
      photothermal therapy were simultaneously driven, resulting in a synergistic
      effect for killing cancer cells. Importantly, compared with chemotherapy or
      photothermal treatment alone, the combined therapy significantly improved the
      therapeutic efficacy. 

PMID- 25970691
TI  - Regulation of a phenylalanine ammonia lyase (BbPAL) by calmodulin in response to
      environmental changes in the entomopathogenic fungus Beauveria bassiana.
AB  - Phenylalanine ammonia lyase (PAL, E.C. 4.3.1.5) catalyses the deamination of L 
      phenylalanine to trans-cinnamic acid and ammonia, facilitating a critical step in
      the phenylpropanoid pathway that produces a variety of secondary metabolites. In
      this study, we isolated BbPAL gene in the entomopathogenic fungus Beauveria
      bassiana. According to multiple sequence alignment, homology modelling and in
      vitro PAL activity, we demonstrated that BbPAL acts as a typical PAL enzyme in B.
      bassiana. BbPAL interacted with calmodulin (CaM) in vitro and in vivo, indicating
      that BbPAL is a novel CaM-binding protein. The functional role of CaM in BbPAL
      action was to negatively regulate the BbPAL activity in B. bassiana. High
      performance liquid chromatography analysis revealed that L -phenylalanine was
      reduced and trans-cinnamic acid was increased in response to the CaM inhibitor W
      7. Dark conditions suppressed BbPAL activity in B. bassiana, compared with light.
      In addition, heat and cold stresses inhibited BbPAL activity in B. bassiana.
      Interestingly, these negative effects of BbPAL activity by dark, heat and cold
      conditions were recovered by W-7 treatment, suggesting that the inhibitory
      mechanism is mediated through stimulation of CaM activity. Therefore, this work
      suggests that BbPAL plays a role in the phenylpropanoid pathway mediated by
      environmental stimuli via the CaM signalling pathway. 

PMID- 25970692
TI  - Glycoform Separation and Characterization of Cetuximab Variants by Middle-up Off
      Line Capillary Zone Electrophoresis-UV/Electrospray Ionization-MS.
AB  - Monoclonal antibodies (mAbs) are highly complex glycoproteins that present a wide
      range of microheterogeneities that requires multiple analytical methods for full
      structure assessment and quality control. Capillary zone electrophoresis-mass
      spectrometry (CZE-MS) couplings, especially by electrospray ionization (ESI),
      appear to be really attractive methods for the characterization of biological
      samples. However, due to the presence of non- or medium volatile salts in the
      background electrolyte (BGE), online CZE-ESI-MS coupling is difficult to
      implement for mAbs isoforms separation. Here, we report an original strategy to
      perform off-line CZE-ESI-MS using CZE-UV/fraction collection technology to
      perform CZE separation, followed by ESI-MS infusion of the different fractions
      using the capillary electrophoresis-electrospray ionization (CESI) interface as
      the nanoESI infusion platform. As the aim is to conserve electrophoretic
      resolution and complete compatibility with ESI-MS without sample treatment,
      hydroxypropylcellulose (HPC) coated capillary was used to prevent analyte
      adsorption and asymmetric CZE conditions involving different BGE at both ends of
      the capillary have been developed. The efficiency of our strategy was validated
      with the separation of Cetuximab charge variant by the middle-up approach.
      Molecular weights were measured for six charge variants detected in the CZE
      separation of Cetuximab subunits. The first three peaks correspond to Fc/2
      variants with electrophoretic resolution up to 2.10, and the last three peaks
      correspond to F(ab')2 variants with average electrophoretic resolution of 1.05.
      Two Fc/2 C-terminal lysine variants were identified and separated. Moreover,
      separation of Fc/2 fragments allowed the glycoprofiling of the variants with the
      characterization of 7 different glycoforms. Regarding the F(ab')2 domain, 8
      glycoforms were detected and separated in three different peaks following the
      presence of N-glycolyl neuraminic acid residues in some glycan structures. This
      work highlights the potential of CZE technology to perform separation of mAbs
      especially when they carry sialic acid carbohydrates. 

PMID- 25970693
TI  - Nano titania aided clustering and adhesion of beneficial bacteria to plant roots
      to enhance crop growth and stress management.
AB  - A novel use of Titania nanoparticles as agents in the nano interface interaction
      between a beneficial plant growth promoting bacterium (Bacillus amyloliquefaciens
      UCMB5113) and oilseed rape plants (Brassica napus) for protection against the
      fungal pathogen Alternaria brassicae is presented. Two different TiO2
      nanoparticle material were produced by the Sol-Gel approach, one using the
      patented Captigel method and the other one applying TiBALDH precursor. The
      particles were characterized by transmission electron microscopy,
      thermogravimetric analysis, X-ray diffraction, dynamic light scattering and nano
      particle tracking analysis. Scanning electron microscopy showed that the
      bacterium was living in clusters on the roots and the combined energy-dispersive
      X-ray spectroscopy analysis revealed that titanium was present in these cluster
      formations. Confocal laser scanning microscopy further demonstrated an increased
      bacterial colonization of Arabidopsis thaliana roots and a semi-quantitative
      microscopic assay confirmed an increased bacterial adhesion to the roots. An
      increased amount of adhered bacteria was further confirmed by quantitative
      fluorescence measurements. The degree of infection by the fungus was measured and
      quantified by real-time-qPCR. Results showed that Titania nanoparticles increased
      adhesion of beneficial bacteria on to the roots of oilseed rape and protected the
      plants against infection. 

PMID- 25970696
TI  - The coated antiseptic tip (CAT) syringe.
AB  - Catheter-related blood stream infections (CR-BSI) account for 30% of healthcare
      acquired infection (HAI). Colonization of connector hubs and contaminated
      syringes are thought to increase the risk of CR-BSI. The Coated Antiseptic Tip
      (CAT) syringe was developed to decontaminate connector hubs, thereby reducing the
      risk of CR-BSI. Needleless valves (n = 20) and three-way connectors (n = 20) were
      contaminated with common critical care pathogens. At hourly intervals, CAT
      syringes were inserted into the connector hubs and normal saline was injected
      through the connector. This was repeated with control (non-coated) syringes. The
      internal surface of the connector hubs were swabbed at t = 0, t = 1 h and t = 4
      h, inoculated onto blood agar plates and analysed by a blinded microbiologist.
      Growth was counted as the number of colony forming units. Baseline swabbing
      demonstrated 100% bacterial hub colonization in both connectors. The CAT syringe
      showed a significant reduction in CFU growth at 0 and 1 h compared with control
      syringes (p < 0.05). At 4 h, the CAT syringe completely eliminated bacterial
      growth in both of the connector hubs. The CAT syringe can effectively disinfect
      both three-way and needleless connectors.

PMID- 25970695
TI  - Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac
      Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling.
AB  - BACKGROUND: Remodeling of cardiac repolarizing currents, such as the
      downregulation of slowly activating K+ channels (IKs), could underlie ventricular
      fibrillation (VF) in heart failure (HF). We evaluated the role of Iks remodeling
      in VF susceptibility using a tachypacing HF model of transgenic rabbits with Long
      QT Type 1 (LQT1) syndrome. METHODS AND RESULTS: LQT1 and littermate control (LMC)
      rabbits underwent three weeks of tachypacing to induce cardiac myopathy (TICM).
      In vivo telemetry demonstrated steepening of the QT/RR slope in LQT1 with TICM
      (LQT1-TICM; pre: 0.26+/-0.04, post: 0.52+/-0.01, P<0.05). In vivo
      electrophysiology showed that LQT1-TICM had higher incidence of VF than LMC-TICM
      (6 of 11 vs. 3 of 11, respectively). Optical mapping revealed larger APD
      dispersion (16+/-4 vs. 38+/-6 ms, p<0.05) and steep APD restitution in LQT1-TICM
      compared to LQT1-sham (0.53+/-0.12 vs. 1.17+/-0.13, p<0.05). LQT1-TICM developed
      spatially discordant alternans (DA), which caused conduction block and higher
      frequency VF (15+/-1 Hz in LQT1-TICM vs. 13+/-1 Hz in LMC-TICM, p<0.05). Ca2+ DA
      was highly dynamic and preceded voltage DA in LQT1-TICM. Ryanodine abolished DA
      in 5 out of 8 LQT1-TICM rabbits, demonstrating the importance of Ca2+ in complex
      DA formation. Computer simulations suggested that HF remodeling caused Ca2+
      driven alternans, which was further potentiated in LQT1-TICM due to the lack of
      IKs. CONCLUSIONS: Compared with LMC-TICM, LQT1-TICM rabbits exhibit steepened APD
      restitution and complex DA modulated by Ca2+. Our results strongly support the
      contention that the downregulation of IKs in HF increases Ca2+ dependent
      alternans and thereby the risk of VF.

PMID- 25970694
TI  - Do housekeeping genes exist?
AB  - The searching of human housekeeping (HK) genes has been a long quest since the
      emergence of transcriptomics, and is instrumental for us to understand the
      structure of genome and the fundamentals of biological processes. The resolved
      genes are frequently used in evolution studies and as normalization standards in
      quantitative gene-expression analysis. Within the past 20 years, more than a
      dozen HK-gene studies have been conducted, yet none of them sampled human tissues
      completely. We believe an integration of these results will help remove false
      positive genes owing to the inadequate sampling. Surprisingly, we only find one
      common gene across 15 examined HK-gene datasets comprising 187 different tissue
      and cell types. Our subsequent analyses suggest that it might not be appropriate
      to rigidly define HK genes as expressed in all tissue types that have diverse
      developmental, physiological, and pathological states. It might be beneficial to
      use more robustly identified HK functions for filtering criteria, in which the
      representing genes can be a subset of genome. These genes are not necessarily the
      same, and perhaps need not to be the same, everywhere in our body. 

PMID- 25970698
TI  - Validity of a neurological scoring system for canine X-linked myotubular
      myopathy.
AB  - A simple clinical neurological test was developed to evaluate response to gene
      therapy in a preclinical canine model of X-linked Myotubular Myopathy (XLMTM).
      This devastating congenital myopathy is caused by mutation in the myotubularin
      (MTM1) gene. Clinical signs include muscle weakness, early respiratory failure
      and ventilator dependence. A spontaneously occurring canine model has a similar
      clinical picture and histological abnormalities on muscle biopsy compared to
      patients. We developed a neuromuscular assessment score, graded on a scale from
      10 (normal) to 1 (unable to maintain sternal recumbency). We hypothesize that
      this neurological assessment score correlates with genotype and established
      measures of disease severity and is reliable when performed by an independent
      observer. At 17 weeks of age, there was strong correlation between neurological
      assessment scores and established methods of severity testing. The neurological
      severity score correctly differentiated between XLMTM and wild type dogs with
      good interobserver reliability, on the basis of strong agreement between
      neurological scores assigned by independent observers. Together, these data
      indicate that the neurological scoring system developed for this canine
      congenital neuromuscular disorder is reliable and valid. This scoring system may
      be helpful in evaluating response to therapy in preclinical testing in this
      disease model, such as response to gene therapy.

PMID- 25970697
TI  - Transcranial direct current stimulation of the posterior parietal cortex
      modulates arithmetic learning.
AB  - The successful acquisition of arithmetic skills is an essential step in the
      development of mathematical competencies and has been associated with neural
      activity in the left posterior parietal cortex (PPC). It is unclear, however,
      whether this brain region plays a causal role in arithmetic skill acquisition and
      whether arithmetic learning can be modulated by means of non-invasive brain
      stimulation of this key region. In the present study we addressed these questions
      by applying transcranial direct current stimulation (tDCS) over the left PPC
      during a short-term training that simulates the typical path of arithmetic skill
      acquisition (specifically the transition from effortful procedural to memory
      based problem-solving strategies). Sixty participants received either anodal,
      cathodal or sham tDCS while practising complex multiplication and subtraction
      problems. The stability of the stimulation-induced learning effects was assessed
      in a follow-up test 24 h after the training. Learning progress was modulated by
      tDCS. Cathodal tDCS (compared with sham) decreased learning rates during training
      and resulted in poorer performance which lasted over 24 h after stimulation.
      Anodal tDCS showed an operation-specific improvement for subtraction learning.
      Our findings extend previous studies by demonstrating that the left PPC is
      causally involved in arithmetic learning (and not only in arithmetic performance)
      and that even a short-term tDCS application can modulate the success of
      arithmetic knowledge acquisition. Moreover, our finding of operation-specific
      anodal stimulation effects suggests that the enhancing effects of tDCS on
      learning can selectively affect just one of several cognitive processes mediated
      by the stimulated area.

PMID- 25970699
TI  - Nurses' views of factors affecting sleep for hospitalized children and their
      families: A focus group study.
AB  - Light, noise, and interruptions from hospital staff lead to frequent awakenings
      and detrimental changes to sleep quantity and quality for children who are
      hospitalized and their parents who stay with them overnight. An understanding of
      nurses' views on how care affects sleep for the hospitalized child and parent is
      crucial to the development of strategies to decrease sleep disturbance in
      hospital. The purpose of this descriptive qualitative study was to gain an
      understanding of nurses' views on their role in and influence on sleep for
      families; perceived barriers and facilitators of patient and parent sleep at
      night; strategies nurses use to preserve sleep; the distribution, between parent
      and nurse, of care for the child at night; views of the parent as a recipient of
      nursing care at night; and the nature of interactions between nurses and families
      at night. Thirty registered nurses from general pediatric and critical care units
      participated in one of four semi-structured focus groups. Four main influences on
      sleep were identified: child factors; environmental factors; nurse-parent
      interaction factors; and nursing care factors. Some of these restricted nurses'
      ability to optimize sleep, but many factors were amenable to intervention.
      Balancing strategies to preserve sleep with the provision of nursing assessment
      and intervention was challenging and complicated by the difficult nature of work
      outside of usual waking hours. Nurses highlighted the need for formal policy and
      mentoring related to provision of nursing care at night in pediatric settings.

PMID- 25970701
TI  - Linking root traits to nutrient foraging in arbuscular mycorrhizal trees in a
      temperate forest.
AB  - The identification of plant functional traits that can be linked to ecosystem
      processes is of wide interest, especially for predicting vegetational responses
      to climate change. Root diameter of the finest absorptive roots may be one plant
      trait that has wide significance. Do species with relatively thick absorptive
      roots forage in nutrient-rich patches differently from species with relatively
      fine absorptive roots? We measured traits related to nutrient foraging (root
      morphology and architecture, root proliferation, and mycorrhizal colonization)
      across six coexisting arbuscular mycorrhizal (AM) temperate tree species with and
      without nutrient addition. Root traits such as root diameter and specific root
      length were highly correlated with root branching intensity, with thin-root
      species having higher branching intensity than thick-root species. In both
      fertilized and unfertilized soil, species with thin absorptive roots and high
      branching intensity showed much greater root length and mass proliferation but
      lower mycorrhizal colonization than species with thick absorptive roots. Across
      all species, fertilization led to increased root proliferation and reduced
      mycorrhizal colonization. These results suggest that thin-root species forage
      more by root proliferation, whereas thick-root species forage more by mycorrhizal
      fungi. In mineral nutrient-rich patches, AM trees seem to forage more by
      proliferating roots than by mycorrhizal fungi. 

PMID- 25970700
TI  - A systematic review and meta-analysis of the effect of statins on plasma
      asymmetric dimethylarginine concentrations.
AB  - The impact of statin therapy on plasma asymmetric dimethylarginine (ADMA) levels
      has not been conclusively studied. Therefore the aim of the meta-analysis was to
      assess the effect of statins on circulating ADMA levels. We searched selected
      databases (up to August 2014) to identify randomized controlled trials (RCTs)
      that investigate the effect of statins on plasma ADMA concentrations. A weighted
      meta-regression (WMD) using unrestricted maximum likelihood model was performed
      to assess the impact of statin dose, duration of statin therapy and baseline ADMA
      concentrations as potential variables on the WMD between statin and placebo
      group. In total, 1134 participants in 9 selected RCTs were randomized; 568 were
      allocated to statin treatment and 566 were controls. There was a significant
      reduction in plasma ADMA concentrations following statin therapy compared with
      placebo (WMD: -0.104 MUM, 95% confidence interval: -0.131 to -0.077, Z = -7.577,
      p < 0.0001). Subgroups analysis has shown a significant impact of hydrophilic
      statins (WMD: -0.207 MUM, 95%CI: -0.427 to +0.013, Z = -7.250, p < .0001) and a
      non-significant effect of hydrophobic statins (WMD: -0.101 MUM, 95%CI: -0.128 to 
      0.074, Z = -1.845, p = 0.065). In conclusion, this meta-analysis of available
      RCTs showed a significant reduction in plasma ADMA concentrations following
      therapy with hydrophilic statins.

PMID- 25970702
TI  - Mutations in SLC6A17 cause autosomal-recessive intellectual disability.

PMID- 25970703
TI  - Selection of HBsAg-Specific DNA Aptamers Based on Carboxylated Magnetic
      Nanoparticles and Their Application in the Rapid and Simple Detection of
      Hepatitis B Virus Infection.
AB  - Aptamers are short single-stranded DNA or RNA oligonucleotides and can be
      selected from synthetic combinatorial libraries in vitro. They have a high
      binding affinity and specificity for their targets. Agarose gels, nitrocellulose
      membranes, and adsorptive microplates are often used as carriers to immobilize
      targets in the SELEX (systematic evolution of ligands by exponential enrichment)
      process, but the subsequent separation step is tedious and time-consuming.
      Therefore, we used magnetic nanoparticles (MNPs) as carriers to immobilize the
      target, hepatitis B surface antigen (HBsAg), which is convenient for fast
      magnetic separation. In this study, we first selected DNA aptamers against HBsAg
      by immobilizing HBsAg on the surface of carboxylated MNPs. The ssDNA library of
      each selection round was prepared by asymmetric PCR amplification for the next
      selection round. To obtain aptamer sequences, the final selected products were
      purified by gel electrophoresis, then cloned, and sequenced. DNA aptamers that
      specifically bind to HBsAg were successfully obtained after 13 selection rounds.
      The selected aptamers were used to construct a chemiluminescence aptasensor based
      on magnetic separation and immunoassay to detect HBsAg from pure protein or
      actual serum samples. There was a linear relationship between HBsAg concentration
      and chemiluminescent intensity in the range of 1-200 ng/mL. The aptasensor worked
      well even in the presence of interfering substances and was highly specific in
      the detection of HBsAg in serum samples, with a detection limit 0.1 ng/mL lower
      than the 0.5 ng/mL limit of an ELISA in use at the hospital. This aptasensor can
      contribute to better detection of hepatitis B virus infection. 

PMID- 25970704
TI  - Attitudes toward disclosure of medication side effects: a nationwide survey of
      Korean patients, caregivers, and oncologists.
AB  - BACKGROUND: We aimed to compare the views of cancer patients, family caregivers,
      and oncologists about the disclosure of side effects in respect to their
      probability of occurrence, severity, and treatment purpose. We also compared
      attitudes toward potential harm of side effect disclosure, patients' perceived
      ability to understand the risk of the side effects, and informed decision-making
      regarding side effects. METHODS: A national survey was performed with 750 patient
      caregiver dyads (75.5% participation rate) recruited by 134 oncologists in 13
      cancer centers (93% participation rate). Attitudes toward communication of side
      effects were assessed in terms of drug purpose, severity of potential
      complications, and probability of harm. RESULTS: Most patients (82.1-87.0%) and
      caregivers (75.9-81.5%) thought they should be informed of all possible drug side
      effects regardless of risk, severity, or drug purpose and wanted these risks to
      be communicated explicitly. Patients and their caregivers believed that detailed
      explanations of side effects did not harm patients, and further, they believed
      that patients could understand risks and make treatment decision based on that
      information. In contrast, oncologists held less positive attitudes toward
      providing detailed information about drug side effects, especially if they were
      not severe and if the drugs were designed for supportive care. CONCLUSION: Cancer
      patients and family members had different perspectives and preferences regarding
      communication of drug side effects from their oncologists. The data from our
      study can serve as a guide for oncologists in presenting side effects information
      to their patients, as well as a basis for physician training.

PMID- 25970705
TI  - Climate Change and Phenology: Empoasca fabae (Hemiptera: Cicadellidae) Migration
      and Severity of Impact.
AB  - Climate change can benefit individual species, but when pest species are enhanced
      by warmer temperatures agricultural productivity may be placed at greater risk.
      We analyzed the effects of temperature anomaly on arrival date and infestation
      severity of potato leafhopper, Empoasca fabae Harris, a classic new world long
      distance migrant, and a significant pest in several agricultural crops. We
      compiled E. fabae arrival dates and infestation severity data at different states
      in USA from existing literature reviews and agricultural extension records from
      1951-2012, and examined the influence of temperature anomalies at each target
      state or overwintering range on the date of arrival and severity of infestation.
      Average E. fabae arrival date at different states reveal a clear trend along the
      south-north axis, with earliest arrival closest to the overwintering range. E.
      fabae arrival has advanced by 10 days over the last 62 years. E. fabae arrived
      earlier in warmer years in relation to each target state level temperature
      anomaly (3.0 days /  degrees C increase in temperature anomaly). Increased
      temperature had a significant and positive effect on the severity of infestation,
      and arrival date had a marginal negative effect on severity. These relationships
      suggest that continued warming could advance the time of E. fabae colonization
      and increase their impact on affected crops. 

PMID- 25970707
TI  - Oxygenation decreases elastin secretion from rat ductus arteriosus smooth muscle
      cells.
AB  - BACKGROUND: The ductus arteriosus (DA), a fetal arterial connection between the
      main pulmonary artery and the descending aorta, normally closes immediately after
      birth. The oxygen concentration in the blood rises after birth, and in the DA
      this increase in oxygen concentration causes functional closure, which is induced
      by smooth muscle contraction. Previous studies have demonstrated that hypoxia
      and/or oxygenation affect vascular remodeling of various vessels. Therefore, we
      hypothesized that the rise in oxygen concentration would affect the vascular
      structure of the DA due to production of proteins secreted from DA smooth muscle
      cells (SMC). METHODS AND RESULTS: Liquid chromatography-tandem mass spectrometry
      was used to comprehensively investigate the secreted proteins in the supernatant
      of rat DA SMC harvested under hypoxic conditions (1% oxygen) or under normoxic
      conditions (21% oxygen). We found that the rise in oxygen concentration reduced
      the secretion of elastin from DA SMC. On reverse transcription-polymerase chain
      reaction, the expression of elastin mRNA was not significantly changed in DA SMC
      from hypoxic to normoxic conditions. CONCLUSIONS: Given that elastin forms
      internal elastic lamina and elastic fibers in the vascular muscle layers, and
      that a rise in oxygen concentration reduced the secretion of elastin, this
      suggests that the rise in blood oxygen concentration after birth reduces the
      secretion of elastin, and therefore may play a role in DA structural remodeling
      after birth.

PMID- 25970708
TI  - Developmental focus on disorders of sex development: special issue overview.

PMID- 25970706
TI  - Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining
      intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and Wnt
      beta-catenin signaling pathways.
AB  - Abnormal proliferation is one characteristic of cancer-associated fibroblasts
      (CAFs), which play a key role in tumorigenesis and tumor progression. Oxidative
      stress (OS) is the root cause of CAFs abnormal proliferation. ATM (ataxia
      telangiectasia mutated protein kinase), an important redox sensor, is involved in
      DNA damage response and cellular homeostasis. Whether and how oxidized ATM
      regulating CAFs proliferation remains unclear. In this study, we show that there
      is a high level of oxidized ATM in breast CAFs in the absence of double-strand
      breaks (DSBs) and that oxidized ATM plays a critical role in CAFs proliferation.
      The effect of oxidized ATM on CAFs proliferation is mediated by its regulation of
      cellular redox balance and the activity of the ERK, PI3K-AKT, and Wnt signaling
      pathways. Treating cells with antioxidant N-acetyl-cysteine (NAC) partially
      rescues the proliferation defect of the breast CAFs caused by ATM deficiency.
      Administrating cells with individual or a combination of specific inhibitors of
      the ERK, PI3K-AKT, and Wnt signaling pathways mimics the effect of ATM deficiency
      on breast CAF proliferation. This is mainly ascribed to the beta-catenin
      suppression and down-regulation of c-Myc, thus further leading to the decreased
      cyclinD1, cyclinE, and E2F1 expression and the enhanced p21(Cip1) level. Our
      results reveal an important role of oxidized ATM in the regulation of the
      abnormal proliferation of breast CAFs. Oxidized ATM could serve as a potential
      target for treating breast cancer. 

PMID- 25970709
TI  - New genomic technologies: an aid for diagnosis of disorders of sex development.
AB  - The Chicago Consensus Conference of 2005 defined Disorders of Sex Development
      (DSD) as "congenital conditions in which the development of chromosomal, gonadal
      or anatomic sex is atypical." DSD diagnoses are difficult to establish. A lack of
      standardization of anatomical and endocrine phenotyping and the limited number of
      known DSD genes and genotype/correlation has long hampered the field, leaving
      many patients without a definitive diagnosis. The resulting uncertainty may
      intrinsically pose a great amount of discomfort to affected individuals and their
      families. DSD-causative genes have historically been identified thanks to
      positional cloning of disease-associated variants segregating in families or
      chromosomal rearrangements. Recent advances of chromosomal microarray and exome
      sequencing technologies are allowing for higher rates of diagnostic success for
      DSD patients and are changing clinical practice. In this review, we discuss the
      application of these technologies and their findings as an upcoming model for
      clinical diagnosis of DSD. We show that exome sequencing is a valuable tool and
      we propose that it should be used as a first-stage diagnostic technique because
      it allows for early identification of a genetic cause that may be critical for
      patient management. 

PMID- 25970710
TI  - Review of current surgical techniques and medical management considerations in
      the treatment of pediatric patients with disorders of sex development.

PMID- 25970711
TI  - Ethical issues in decision-making for infants with disorders of sex development.
AB  - Medical decisions for infants and children should generally be based on the best
      interests of the child. When there is legitimate controversy over the child's
      best interests, the right of the child to an open future should generally
      determine the course of treatment. In the case of infants born with disorders of
      sex development (DSD), early cosmetic genitoplasty was long believed to be in the
      child's best interest and was therefore the standard of care. New data suggest
      that early genitoplasty may be more harmful than helpful, therefore the best
      interest standard is no longer determinative in such cases. Because children born
      with DSD have a right to an open future, and because the openness of their future
      is clearly enhanced by delaying cosmetic genitoplasty until they themselves can
      participate meaningfully in decision-making, early genitoplasty is ethically
      supportable only when medically indicated (e.g., when the child is unable to
      urinate without surgical intervention). Further research is needed to clarify the
      benefits and burdens of early and delayed genitoplasty. In parallel with further
      research, efforts should focus on educating society broadly to decrease
      stigmatization of persons with DSD.

PMID- 25970712
TI  - Disorders of Sex Development (DSD): Peer Relations and Psychosocial Well-Being.
AB  - Social and emotional development is shaped by familial and extra-familial
      experiences especially interactions with peers. Children and adolescents with
      physical, behavioral or developmental differences, such as youth with disorders
      of sex development (DSD), may not benefit to the same degree as other children
      and adolescents from experiences with peers. This paper reviews current thinking
      about the features and effects of experiences with peers and the potential
      challenges of peer interactions for children and adolescents with DSD. We review
      findings from studies of adjustment for individuals with DSD. We finish the paper
      with a brief outline of a research agenda to promote the understanding of
      adjustment of individuals with DSD. 

PMID- 25970713
TI  - Disorders of Sex Development (DSD): Networking and Standardization
      Considerations.
AB  - Syndromes resulting in Disorders of Sex Development (DSD) are individually rare.
      Historically, this fact has hindered both clinical research and the delivery of
      evidence-based care. Recognizing the need for advancement, members of European
      and North American medical societies produced policy statements, notably the
      Consensus Statement on Management of Intersex Disorders, which recognize that
      optimal healthcare in DSD requires multidisciplinary teams in conjunction with
      networking of treatment centers and continued development of patient registries.
      This paper summarizes efforts in Europe and the U.S. toward creating networks
      focused on expanding discovery and improving healthcare and quality of life
      outcomes in DSD. The objectives and function of registry-based networks
      (EuroDSD/I-DSD), learning collaboratives (DSD-net), clinical outcomes research
      (DSD-Life), and networking hybrids (DSD-TRN) are reviewed. Opportunities for, and
      barriers to standardization in research and care are highlighted in light of
      practical considerations, for example, limitations in reliably classifying
      anatomic phenotypes and gaps in behavioral health staffing resources. The role of
      patient-reported outcomes is considered, with emphasis on integrating patient
      perspectives, given findings of limited agreement in outcome ratings by
      healthcare providers and patients. Finally, the characteristics of clinical
      centers likely to deliver the highest quality outcomes are discussed. 

PMID- 25970714
TI  - Platelet receptors and patient responses: The contributions of Professor Stan
      Heptinstall to platelet research.
AB  - Stan Heptinstall's contributions to platelet research covered organising meetings
      at the national and European level as well as starting and maintaining the
      journal "Platelets". The major part of his research addressed problems of
      inhibition of platelet receptors and the effects of this on patient health. In
      particular, the effects of P2Y12 inhibitors on patients with acute cardiovascular
      problems were a major focus. Other studies included the effects of feverfew
      (Tanacetum parthenium) extracts on platelets, of direct anti-IIb/IIIa receptor
      (alphaIIbbeta3) inhibitors and of prostanoids on platelet function. Recently,
      methods for assessing the effectiveness of platelet inhibition were investigated.

PMID- 25970715
TI  - Serological criteria and carriage measurement for evaluation of new pneumococcal
      vaccines.
AB  - The best method of evaluating the efficacy of a vaccine is to compare the
      incidence of the disease against which it is prepared in randomized, placebo
      controlled clinical trials involving vaccinated and unvaccinated subjects. In the
      case of Streptococcus pneumoniae, the proposed alternatives are evaluations of
      the so-called "correlates of protection" (i.e. markers of the vaccine-induced
      immune response that predict protection from infection and disease) and
      nasopharyngeal carriage. The aim of this paper is to discuss the most important
      limitations of the immunological criteria suggested for licensing new
      pneumococcal vaccines, and comment on the use of carriage as an endpoint for
      evaluating efficacy. Data showed why the use of a single serological correlate of
      protection cannot be considered the best means of evaluating pneumococcal
      vaccines and highlighted the importance of using carriage for efficacy evaluation
      but in the meantime the need to develop new sensitive and specific methods. 

PMID- 25970716
TI  - Drastically Enhanced High-Rate Performance of Carbon-Coated LiFePO4 Nanorods
      Using a Green Chemical Vapor Deposition (CVD) Method for Lithium Ion Battery: A
      Selective Carbon Coating Process.
AB  - Application of LiFePO4 (LFP) to large current power supplies is greatly hindered
      by its poor electrical conductivity (10(-9) S cm(-1)) and sluggish Li+ transport.
      Carbon coating is considered to be necessary for improving its interparticle
      electronic conductivity and thus electrochemical performance. Here, we proposed a
      novel, green, low cost and controllable CVD approach using solid glucose as
      carbon source which can be extended to most cathode and anode materials in need
      of carbon coating. Hydrothermally synthesized LFP nanorods with optimized
      thickness of carbon coated by this recipe are shown to have superb high-rate
      performance, high energy, and power densities, as well as long high-rate cycle
      lifetime. For 200 C (18s) charge and discharge, the discharge capacity and
      voltage are 89.69 mAh g(-1) and 3.030 V, respectively, and the energy and power
      densities are 271.80 Wh kg(-1) and 54.36 kW kg(-1), respectively. The capacity
      retention of 93.0%, and the energy and power density retention of 93.6% after 500
      cycles at 100 C were achieved. Compared to the conventional carbon coating
      through direct mixing with glucose (or other organic substances) followed by
      annealing (DMGA), the carbon phase coated using this CVD recipe is of higher
      quality and better uniformity. Undoubtedly, this approach enhances significantly
      the electrochemical performance of high power LFP and thus broadens greatly the
      prospect of its applications to large current power supplies such as electric and
      hybrid electric vehicles.

PMID- 25970717
TI  - [Molecular pathology of endometrial carcinoma - a review].
AB  - Endometrial carcinoma (EC) is the most common malignancy of the female genital
      tract in developed countries. According to its histomorphologic characteristics
      EC is divided into endometroid and serous carcinoma; among less common subtypes
      there are clear cell, mucinous, neuroendocrine and undifferentiated carcinoma and
      carcinosarcoma. Endometroid and serous EC were essential for the so-called dual
      classification of EC (type I and type II), which considered mainly
      epidemiological, clinical and endocrine characteristics. It was shown that part
      of the high-grade serous carcinomas (type II) can develop from the endometroid EC
      by a multiplication of genomic changes and there are also EC, in which both basic
      types are overlapping. Today it is known that clinical and histological
      presentation of the EC reflects the genetic and epigenetic alterations affecting
      mainly PTEN, PIK3CA, KRAS, CTNNB1 and TP53 genes, or leading to microsatellite
      instability. However, these changes are variably present in both types of EC;
      therefore dual division of EC has appeared very rigid. The novel classifications
      should represent an integrated system which also incorporates the results of the
      gene expression analyses and multiparallel DNA sequencing. Based on these
      findings EC were divided into four molecular categories: a) POLE/ultra mutated;
      b) hyper mutated microsatellite instable; c) "copy number low" d) "copy number
      high" serous-like carcinoma. This division better reflects the biological
      characteristics of each EC and represents a base for the individual therapy. 

PMID- 25970718
TI  - [Practical comments on examination of placenta in the second and third trimester
      of gravidity].
AB  - The authors present a short summary of placental pathology for the general
      pathologist. Practical tips for macroscopic examination of formalin-fixed
      material are listed and several cases are presented for illustration of the
      theoretical text. 

PMID- 25970719
TI  - EGFR in triple negative breast carcinoma: significance of protein expression and
      high gene copy number.
AB  - BACKGROUND: As up to 60 % of triple negative breast carcinomas are reported to
      express EGFR, the receptor is a potential target for biological therapy. The
      exact role EGFR plays in triple negative breast carcinoma (TNBC) biology,
      however, remains uncertain. We aimed to discover associations between EGFR
      protein expression as well as gene copy number changes and clinico-pathologic
      TNBC characteristics. METHODS: We performed an immunohistochemical and dual in
      situ hybridization study on a set of 52 archive cases of pre-treatment TNBC in
      order to detect EGFR protein expression and EGFR gene copy number changes.
      Clinico-pathologic and follow up data were compared with EGFR status for
      determining possible links between EGFR and tumor characteristics and/or
      behavior. RESULTS: 88.5 % of our cases showed EGFR expression. We found no
      significant links between EGFR expression and tumor grade (p = 0.204), lymph node
      status (p = 0.514) or p53 status (p = 0.078). Though EGFR gene amplification
      (EGFR gene:chromosome 7 ratio 2) was rare (1.9 % of all cases), a high gene copy
      number ( 4 copies per cell) was observed in 15.4 % of all cases. High EGFR gene
      copy number appeared to be more common in non-ductal, special-type carcinomas
      than in ductal carcinomas. Neither EGFR expression nor EGFR gene copy number was
      associated with event-free survival. CONCLUSION: EGFR changes do not appear to be
      associated with markers of aggressive behavior in TNBC. Further studies with much
      larger sample sizes are essential in understanding the role EGFR plays in TNBC
      biology in order to identify the patients that could benefit from EGFR targeted
      therapy.

PMID- 25970720
TI  - Celiac disease-like enteropathy due to antihypertensive therapy with the
      angiotensin-II receptor type 1 inhibitor eprosartan.
AB  - An 83-year-old woman with hypertension received the angiotensin-II receptor type
      1 blocker (ARB) eprosartan for more than 10 years. Six months ago, the dosage of
      the drug was doubled, and the patient reported a sudden onset of diarrhea.
      Duodenal biopsies showed a celiac disease-like pathology with flattened mucosa
      and an increase of intraepithelial lymphocytes and eosinophils, but serology of
      celiac disease remained negative. Celiac disease-like changes have been
      previously reported to be associated with other ARBs. This is the first case
      following eprosartan medication. In celiac-disease-like pathology of the small
      bowel with negative serology, drug-induced changes, for example due to ARBs,
      should be excluded. 

PMID- 25970721
TI  - [Unusual lung finding of massive alveolar filling with foamy macrophages in
      congenital epidermolysis bullosa after amnion fluid aspiration in 15-day-old
      newborn without any clinical signs of respiratory impairment].
AB  - Epidermolysis bullosa represents a group of mechanobullous diseases which are
      most commonly genetically determined. We describe the case of a 15-day-old female
      newborn with congenital epidermolysis bullosa which was inflicted on aproximately
      1/3 of her skin surface, who died because of incorrigible sepsis with multiorgan
      failure. The main topic of our report is a description of an unusual pulmonary
      finding of massive alveolar filling with foamy macrophages after amnion fluid
      aspiration, which contained a excessive amount of desquamated epidermal cells.
      Introduced case shows outstanding discrepancy of negative clinical finding on one
      side and massive histopathological finding on the other. 

PMID- 25970722
TI  - [Microvascular density in lymphomas - evaluation methods and clinical impact].
AB  - In recent years antiangiogenic therapy has become a part of treatment protocols
      of solid tumors as well as of lymphomas. This is why tumor vascularization has
      been explored, the most important parameters to describe it being the
      microvascular density and immunohistochemical assessment of the expression of
      VEGF (vascular endothelial growth factor) and of its receptors. This review
      summarizes various methods of assessment of the microvascular density and the
      prognostic impact of microvascular density in lymphomas. 

PMID- 25970723
TI  - A regioselective facile synthesis of furo[3,4-b]carbazolones: application to the
      total synthesis of mafaicheenamine E and claulansine D.
AB  - 1-Hydroxycarbazole-2,3-dicarboxylates have been shown to undergo chemoselective
      reductive cyclization to furo[3,4-b]carbazolones on reaction with LiAlH4. One of
      the furocarbazolones is utilized to accomplish the first total synthesis of
      claulansine D and mafaicheenamine E in 9 and 6 steps respectively. The other key
      steps of the syntheses are addition of an allylic indium reagent and CC double
      bond isomerization. 

PMID- 25970724
TI  - Re: The diagnostic skills of fourteen-year olds.

PMID- 25970725
TI  - Web-based assessment of Parkinson's prodromal markers identifies GBA variants.

PMID- 25970726
TI  - Omentum ECM-based hydrogel as a platform for cardiac cell delivery.
AB  - Cardiovascular diseases remain the number one killer in Western countries.
      Despite recent advances and promising results in cardiac cell-based therapy, one
      of the remaining challenges is poor cell retention in the desired site. As a
      solution, cell delivery systems are developed to ensure that a sufficient number
      of viable cells reach the infarct area. These delivery systems are based on
      biomaterials that provide a surrogate microenvironment for the encapsulated
      cells, retaining them in the desired location post-delivery. Injectable
      thermoresponsive ECM-based hydrogels have been developed to achieve this goal.
      Unfortunately, the use of allogeneic or xenogeneic ECM may hamper the treatment
      due to an immune response to residual cellular content from the host. In this
      work, we have developed an omentum-based hydrogel capable of self-assembly under
      physiological conditions. Although in this study the omentum was obtained from
      porcine sources, it can be easily and safely extracted from the patient, serving
      as an autologous protective vehicle for the transported cells. We have
      characterized the biochemical composition, mechanical properties, and gelation
      and degradation kinetics of the processed biomaterial. Furthermore, the ability
      of the hydrogel to encapsulate cardiac cells and support their culture was
      evaluated. We envision that the newly developed platform may open new
      opportunities for personalized cell delivery to the heart and other tissues. 

PMID- 25970727
TI  - Dermatosis Caused by Blood-Sucking Corythucha Ciliata.

PMID- 25970728
TI  - A national survey of public views about the classification of obesity as a
      disease.
AB  - OBJECTIVE: In 2013, the American Medical Association classified obesity as a
      disease. This study assessed public opinions about this disease classification.
      METHODS: In January 2014, a national sample of 1118 adults completed surveys
      assessing their agreement with 33 statements in support of and against the
      disease classification of obesity, as well as measures assessing sociodemographic
      characteristics. RESULTS: The majority of participants (51-61.7%) agreed with 11
      of 17 statements in support of the disease classification of obesity (average
      agreement across all statements = 51%), including views that it will help people
      gain access to obesity treatment. A minority of participants (31-47.3%) agreed
      with 15 of 16 statements against the disease classification (average agreement
      across statements = 39.5%), including views that it will increase overreliance on
      medications or surgery to treat obesity (47.3%). Participants' attitudes were
      unaffected by sex, income, education, or health status but were related to causal
      beliefs about obesity. The disease classification received more support from
      African Americans and more opposition by individuals with higher weight stigma.
      CONCLUSIONS: This study found more public agreement supporting the disease
      classification of obesity than opposing it. Further work should identify whether
      this classification affects health behaviors among individuals with obesity or
      societal weight stigmatization.

PMID- 25970729
TI  - Limonoids with Anti-HIV Activity from Cipadessa cinerascens.
AB  - Sixteen new limonoids, named ciparasins A-P (1-16), comprising three structural
      categories of trijugin-type (1-7), cipadesin-type (8-15), and prieurianin-type
      (16) compounds, as well as 15 known limonoid analogues (17-31), were isolated
      from Cipadessa cinerascens. Ciparasins E-G (5-7) were found to possess a rare
      gamma-hydroxylbutenolide moiety at C-17. Ciparasins B (2) and P (16) showed
      significant anti-HIV activities, with EC50 values of 5.5 +/- 0.6 (SI >7.2) and
      6.1 +/- 0.7 (SI >6.5) MUM, respectively. 

PMID- 25970733
TI  - Significance of C4d Immunostaining in Placental Chronic Intervillositis.
AB  - Deposition of the complement split product C4d is a phenomenon studied
      extensively as a marker for complement activation in antibody-mediated transplant
      rejection. C4d also is observed in placental disease processes including
      spontaneous abortion, infarct, and villitis of unknown origins. Massive chronic
      intervillositis is a rare placental abnormality associated with increased risk of
      growth restriction, fetal death, and recurrent fetal loss. In this study, we
      evaluated C4d immunostaining in placentas with accumulation of intervillous
      monocytes with and without villitis. Archived placentas from Kosair Children's
      Hospital (Louisville, KY) and Seattle Children's Hospital (Seattle, WA) were
      selected and divided into 4 groups, 16 cases of intervillositis with complicated
      pregnancy, 15 cases of uncomplicated intervillositis, 20 cases of complicated
      villitis, and 13 cases of uncomplicated villitis, all with varying degrees of
      monocytic cells in the intervillous space. Representative specimen blocks were
      immunohistochemically stained for C4d. The percentage of positive staining of the
      microvillous surface of the syncytiotrophoblast was scored by five pathologists,
      and the following consensus score was determined: 0  =  0% to 5%; 1  =  5% to
      25%; 2  =  25% to 75%; and 3 >= 75%. C4d immunostain localized to the
      microvillous border of syncytiotrophoblast in many of the placentas. C4d staining
      was more strongly associated with intervillositis than with villitis (odds ratio:
      6.3; confidence interval: 2.1-18.7; P  =  0.001). 

PMID- 25970734
TI  - Reply: To PMID 25041865.

PMID- 25970732
TI  - Chemical cross-linking and native mass spectrometry: A fruitful combination for
      structural biology.
AB  - Mass spectrometry (MS) is becoming increasingly popular in the field of
      structural biology for analyzing protein three-dimensional-structures and for
      mapping protein-protein interactions. In this review, the specific contributions
      of chemical crosslinking and native MS are outlined to reveal the structural
      features of proteins and protein assemblies. Both strategies are illustrated
      based on the examples of the tetrameric tumor suppressor protein p53 and
      multisubunit vinculin-Arp2/3 hybrid complexes. We describe the distinct
      advantages and limitations of each technique and highlight synergistic effects
      when both techniques are combined. Integrating both methods is especially useful
      for characterizing large protein assemblies and for capturing transient
      interactions. We also point out the future directions we foresee for a
      combination of in vivo crosslinking and native MS for structural investigation of
      intact protein assemblies. 

PMID- 25970735
TI  - Reply: To PMID 25086190.

PMID- 25970736
TI  - Enlightening the Mechanism of Copper Mediated PhotoRDRP via High-Resolution Mass
      Spectrometry.
AB  - The initiation mechanism of photochemically mediated Cu-based reversible
      deactivation radical polymerization (photoRDRP) was investigated using pulsed
      laser polymerization (PLP) and high-resolution mass spectrometry. The variation
      of the catalyst composition and ESI-MS analysis of the resulting products
      provided information on how initiator, ligand, copper species, and monomer are
      interacting upon irradiation with UV light. A discussion of the results allows
      for a new postulation of the mechanism of photoRDRP and-for the first time-the
      unambiguous identification of the initiating species and their interactions
      within the reaction mixture. One pathway for radical generation proceeds via UV
      light-induced C-Br bond scission of the initiator, giving rise to propagating
      radicals. The generation of copper(I) species from copper(II) can occur via
      several pathways, including, among others, via reduction by free amine ligand in
      its excited as well as from its ground state via the irradiation with UV light.
      The amine ligand serves as a strong reducing agent and is likely the main
      participant in the generation of copper(I) species. 

PMID- 25970737
TI  - ABCDE, but in that order? A cross-sectional survey of Michigan intensive care
      unit sedation, delirium, and early mobility practices.
AB  - RATIONALE: A bundled approach to intensive care unit (ICU) care known as
      "Awakening and Breathing Coordination, Delirium monitoring/management, and Early
      exercise/mobility" (ABCDE) has been proposed, with evidence supporting individual
      interventions as well as the bundle as a whole. Few data exist on the bundle's
      implementation and efficacy in community practice. OBJECTIVES: To evaluate self
      reported rates of implementation of ABCDE components and their association with
      outcomes in a state-wide quality improvement collaborative. METHODS: A written
      survey was administered to representatives attending the 2012 annual meeting of
      the Michigan Health and Hospital Association's Keystone ICU collaborative.
      Respondents reported on their practices regarding spontaneous awakening trials,
      delirium assessments, and early mobility. MEASUREMENTS AND MAIN RESULTS: There
      were 212 respondents, a 76% response rate. Wide variation in focus was noted
      across the assessed components of ABCDE. Only 12% reported having implemented
      routine spontaneous awakening trials and delirium assessments as well as early
      mobility, 36% reported not having early mobility as an active goal in their units
      (nonmovers), and 52% reported attempts at early mobility without both routine
      sedation interruption and delirium screening implementation. In adjusted models,
      those who implemented exercise with sedation interruption and delirium screening
      were 3.5 (95% confidence interval, 1.4-8.6) times more likely to achieve higher
      levels of exercise in ventilated patients than those who implemented exercise
      without both sedation interruption and delirium screening. CONCLUSIONS: There is
      incomplete penetrance of aspects of ABCDE across ICUs in this highly motivated
      statewide quality improvement collaborative. Yet, implementation of exercise in
      the context of both sedation interruption and delirium screening was associated
      with improved self-reported mobility outcomes. Effective knowledge translation
      and implementation strategies may offer substantial benefits to ICU patients.

PMID- 25970738
TI  - Effect of an intervention mapping approach to promote the consumption of fruits
      and vegetables among young adults in junior college: A quasi-experimental study.
AB  - OBJECTIVE: This study evaluates the effectiveness of an intervention mapping
      developed to promote fruit and vegetable consumption. DESIGN: Students (n = 394)
      from two similar public colleges in the Quebec City area (Canada) were asked to
      participate. A quasi-experimental design was used with a 14-week pause between
      the pretest and posttest. The control and experimental groups both received
      information on Canada's Food Guide recommendations. The experimental group was
      submitted to an intervention consisting of six interactive workshops carried out
      inside the college, and three personal exercises to be completed at home. MAIN
      OUTCOME: proportion of respondents consuming at least five servings of fruits and
      vegetables daily. SECONDARY OUTCOMES: psychosocial variables assessed (theory of
      planned behaviour). RESULTS: The data collected from 344 participants by means of
      a self-administered questionnaire were analysed (167 experimental and 177
      control). The posttest revealed a significant increase (15%) in the number of
      participants in the experimental group achieving the primary outcome (d = .38).
      The intervention also had a significant effect on the targeted psychosocial
      variables (eta(2) = .03 to .06). Regularity of consumption acts as a mediator
      between intention and behaviour. CONCLUSION: These results may be used to guide
      health promoters working with college students.

PMID- 25970739
TI  - Magnetic Interaction of Transition Ion Salts with Spin Labeled Lipid Membranes:
      Interplay of Anion-Specific Adsorption, Electrostatics, and Membrane Fluidity.

PMID- 25970731
TI  - Chemical biology of protein arginine modifications in epigenetic regulation.

PMID- 25970740
TI  - Correction to Effect of Calcination Conditions on Porous Reduced Titanium Oxides
      and Oxynitrides via a Preceramic Polymer Route.

PMID- 25970742
TI  - Poor bone health at the end of puberty in childhood cancer survivors.
AB  - BACKGROUND: Although the survival rate following childhood cancer is >80%, late
      effects are a major concern. We aimed to determine the clinical factors affecting
      bone health after puberty in childhood cancer survivors at risk for low bone
      mineral density (BMD). PROCEDURES: We performed dual-energy X-ray absorptiometry
      at the lumbar spine, femoral neck, and total hip regions for survivors with the
      following bone densitometry indications (BDIXs): brain or nasopharyngeal cancer,
      head or neck area radiotherapy, or corticosteroid treatment (N = 92).
      Additionally, we evaluated 16 survivors without these BDIXs but with other
      clinical factors that could affect bone health. We assessed the effects of these
      factors on BMD using univariate and logistic regression analyses. Moderate BMD
      deficit was defined as a Z-score of <-1.0 and >=-2.0, and severe BMD deficit was
      defined as <-2.0. RESULTS: Severe BMD deficits were found in 18 survivors (16.7%)
      and moderate BMD deficits were in 39 (36.1%) in at least one bone region. BMD
      deficits tended to increase as the number of BDIXs increased (P < 0.010). There
      were no severe BMD deficits in survivors without BDIXs. The duration since cancer
      treatment completion was correlated with higher BMD (P < 0.05). Endocrine
      dysfunction was a significant risk factor for decreased BMD in univariate and
      multivariate analyses (P < 0.05 for both). CONCLUSIONS: Decreased BMD was
      prevalent in our study cohort. Endocrine dysfunction was found to be a
      significant risk factor, and it should be managed in survivors to ensure future
      bone health.

PMID- 25970743
TI  - Surgical treatment of gastrointestinal stromal tumour of the rectum in the era of
      imatinib.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GISTs) of the rectum often require
      radical surgery to achieve complete resection. This study investigated the
      management and outcome of surgery for rectal GISTs and the role of imatinib.
      METHODS: A cohort study was undertaken of patients identified from a database at
      one tertiary sarcoma referral centre over a continuous period, from January 2001
      to January 2013. RESULTS: Over 12 years, 19 patients presented with a primary
      rectal GIST. Median age was 57 (range 30-77) years. Neoadjuvant imatinib was used
      in 15 patients, significantly reducing mean tumour size from 7.6 (95 per cent
      c.i. 6.1 to 9.0) to 4.1 (2.8 to 5.3) cm (P < 0.001). Nine of these patients
      underwent surgical resection. Imatinib therapy enabled sphincter-preserving
      surgery to be undertaken in seven patients who would otherwise have required
      abdominoperineal resection or pelvic exenteration for tumour clearance.
      Neoadjuvant imatinib treatment also led to a significant reduction in mean(s.d.)
      tumour mitotic count from 16(16) to 4(9) per 50 high-power fields (P = 0.015).
      Imatinib was used only as adjuvant treatment in two patients. There were three
      deaths, all from unrelated causes. Eleven of the 13 patients who underwent
      resection were alive without evidence of recurrence at latest follow-up, with a
      median disease-free survival of 38 (range 20-129) months and overall survival of
      62 (39-162) months. CONCLUSION: The use of neoadjuvant imatinib for rectal GISTs
      significantly decreased both tumour size and mitotic activity, which permitted
      less radical sphincter-preserving surgery.

PMID- 25970741
TI  - Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator
      antigen levels among glucose-intolerant women with and without histories of
      gestational diabetes.
AB  - AIM: To examine concentrations of biomarkers (adiponectin, C-reactive protein,
      fibrinogen and tissue plasminogen-activator antigen) associated with glucose
      homeostasis and diabetes risk by history of gestational diabetes (GDM). METHODS:
      We conducted a secondary analysis of the Diabetes Prevention Program, a
      randomized trial of lifestyle intervention or metformin for diabetes prevention.
      At baseline, participants were overweight and had impaired glucose tolerance.
      Biomarkers at baseline and 1 year after enrolment were compared between parous
      women with (n = 350) and without histories of GDM (n = 1466). Cox proportional
      hazard models evaluated whether history of GDM was associated with diabetes risk,
      after adjustment for baseline biomarker levels as well as for change in biomarker
      levels, demographic factors and anthropometrics. RESULTS: At baseline, women with
      histories of GDM had lower adiponectin (7.5 MUg/ml vs. 8.7 MUg/ml; p < 0.0001)
      and greater log C-reactive protein (-0.90 mg/l vs. -0.78 mg/l, p = 0.04) levels
      than women without histories of GDM, but these associations did not persist after
      adjustment for demographic factors. Fibrinogen and tissue plasminogen-activator
      antigen were similar between women with and without histories of GDM. Women with
      and without histories of GDM had a similar pattern of changes in biomarkers
      within randomization arm. Adjustment for age, race/ethnicity, baseline weight,
      change in weight, baseline biomarker level and change in biomarker level did not
      significantly alter the association between history of GDM, and diabetes risk.
      CONCLUSIONS: Among women with impaired glucose tolerance, biomarkers in women
      with and without histories of GDM are similar and respond similarly to lifestyle
      changes and metformin. Adjustment for biomarker levels did not explain the higher
      risk of diabetes observed in women with histories of GDM.

PMID- 25970745
TI  - Release of ecologically relevant metabolites by the cyanobacterium Synechococcus
      elongates CCMP 1631.
AB  - Photoautotrophic plankton in the surface ocean release organic compounds that
      fuel secondary production by heterotrophic bacteria. Here we show that an
      abundant marine cyanobacterium, Synechococcus elongatus, contributes a variety of
      nitrogen-rich and sulfur-containing compounds to dissolved organic matter. A
      combination of targeted and untargeted metabolomics and genomic tools was used to
      characterize the intracellular and extracellular metabolites of S. elongatus.
      Aromatic compounds, such as 4-hydroxybenzoic acid and phenylalanine, as well as
      nucleosides (e.g. thymidine, 5'-methylthioadenosine, xanthosine), the
      organosulfur compound 3-mercaptopropionate, and the plant auxin indole 3-acetic
      acid, were released by S. elongatus at multiple time points during its growth.
      Further, the amino acid kynurenine was found to accumulate in the media even
      though it was not present in the predicted metabolome of S. elongatus. This
      indicates that some metabolites, including those not predicted by an organism's
      genome, are likely excreted into the environment as waste; however, these
      molecules may have broader ecological relevance if they are labile to nearby
      microbes. The compounds described herein provide excellent targets for
      quantitative analysis in field settings to assess the source and lability of
      dissolved organic matter in situ.

PMID- 25970746
TI  - Improving the Quality of Data in Surgical Registries.

PMID- 25970747
TI  - Qualitative Profiling of Polyglucose Degradation Products in Peritoneal Dialysis
      Fluids.
AB  - Heat sterilization of peritoneal dialysis (PD) fluids leads to partial
      degradation of the osmotic agent to form reactive carbonyl structures, which
      significantly reduce the biocompatibility of PD fluids and impair long-term PD
      therapy. Hence, it is important to know the exact composition of the degradation
      products to improve biocompatibility of PD fluids. Our study conducted targeted
      screening for degradation products in polyglucose (icodextrin)-containing PD
      fluids (pGDPs) by applying o-phenylenediamine (OPD) to form stable derivatives,
      which were analyzed by ultrahigh-performance liquid chromatography with
      hyphenated diode array tandem mass spectrometry (UHPLC-DAD-MS/MS). For the first
      time, specific degradation products of polyglucose, namely, 4-deoxyglucosone (4
      DG) and 3,4-dideoxypentosone (3,4-DDPS), could be identified in PD fluids.
      Further, a reaction product of 5-hydroxymethylfurfural (5-HMF) and OPD could be
      characterized to be (5-(1H-benzo[d]imidazol-2-yl)furan-2-yl)methanol.
      Additionally, 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal), both known
      to be present in glucose-based PD fluids, were also detected in polyglucose
      containing fluids. Trapping a hitherto unknown degradation product with OPD
      yielded 1,4-bis(1H-benzo[d]imidazol-2-yl)-3,4-dihydroxybutan-1-one, which was
      present in heat- as well as filter-sterilized PD fluids. 

PMID- 25970748
TI  - ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging
      hematopoietic stem/progenitor cells in mice.
AB  - Iron overload, caused by hereditary hemochromatosis or repeated blood
      transfusions in some diseases, such as beta thalassemia, bone marrow failure and
      myelodysplastic syndrome, can significantly induce injured bone marrow (BM)
      function as well as parenchyma organ dysfunctions. However, the effect of iron
      overload and its mechanism remain elusive. In this study, we investigated the
      effects of iron overload on the hematopoietic stem and progenitor cells (HSPCs)
      from a mouse model. Our results showed that iron overload markedly decreased the
      ratio and clonogenic function of murine HSPCs by the elevation of reactive oxygen
      species (ROS). This finding is supported by the results of NAC or DFX treatment,
      which reduced ROS level by inhibiting NOX4 and p38MAPK and improved the long-term
      and multi-lineage engrafment of iron overload HSCs after transplantation.
      Therefore, all of these data demonstrate that iron overload injures the
      hematopoiesis of BM by enhancing ROS through NOX4 and p38MAPK. This will be
      helpful for the treatment of iron overload in patients with hematopoietic
      dysfunction. 

PMID- 25970749
TI  - Frequent epigenetic suppression of tumor suppressor gene glutathione peroxidase 3
      by promoter hypermethylation and its clinical implication in clear cell renal
      cell carcinoma.
AB  - The goal of this study is to identify novel tumor suppressor genes silenced by
      promoter methylation in clear cell renal cell carcinoma (ccRCC) and discover new
      epigenetic biomarkers for early cancer detection. Reactive oxygen species (ROS)
      is a major cause of DNA damage that correlates with cancer initiation and
      progression. Glutathione peroxidase 3 (GPX3), the only known extracellular
      glycosylated enzyme of GPXs, is a major scavenger of ROS. GPX3 has been
      identified as a tumor suppressor in many cancers. However, the role of GPX3 in
      ccRCC remains unclear. This study aimed to investigate its epigenetic alteration
      in ccRCC and possible clinicopathological association. In our study, GPX3
      methylation and down-regulation were detected in 5 out of 6 ccRCC cell lines and
      the GPX3 mRNA and protein expression level in ccRCC tumors was significantly
      lower than in adjacent non-malignant renal tissues (p<0.0001). Treatment with 5
      Aza-2'-deoxycytidine restored GPX3 expression in ccRCC cells. Aberrant
      methylation was further detected in 77.1% (162/210) of RCC primary tumors, but
      only 14.6% (7/48) in adjacent non-malignant renal tissues. GPX3 methylation
      status was significantly associated with higher tumor nuclear grade (p=0.014).
      Thus, our results showing frequent GPX3 inactivation by promoter hypermethylation
      in ccRCC may reveal the failure in the cellular antioxidant system in ccRCC and
      may be associated with renal tumorigenesis. GPX3 tumor specific methylation may
      serve as a biomarker for early detection and prognosis prediction of ccRCC.

PMID- 25970750
TI  - Biohydrogen and Bioethanol Production from Biodiesel-Based Glycerol by
      Enterobacter aerogenes in a Continuous Stir Tank Reactor.
AB  - Crude glycerol from the biodiesel manufacturing process is being produced in
      increasing quantities due to the expanding number of biodiesel plants. It has
      been previously shown that, in batch mode, semi-anaerobic fermentation of crude
      glycerol by Enterobacter aerogenes can produce biohydrogen and bioethanol
      simultaneously. The present study demonstrated the possible scaling-up of this
      process from small batches performed in small bottles to a 3.6-L continuous stir
      tank reactor (CSTR). Fresh feed rate, liquid recycling, pH, mixing speed,
      glycerol concentration, and waste recycling were optimized for biohydrogen and
      bioethanol production. Results confirmed that E. aerogenes uses small amounts of
      oxygen under semi-anaerobic conditions for growth before using oxygen from
      decomposable salts, mainly NH4NO3, under anaerobic condition to produce hydrogen
      and ethanol. The optimal conditions were determined to be 500 rpm, pH 6.4, 18.5
      g/L crude glycerol (15 g/L glycerol) and 33% liquid recycling for a fresh feed
      rate of 0.44 mL/min. Using these optimized conditions, the process ran at a lower
      media cost than previous studies, was stable after 7 days without further
      inoculation and resulted in yields of 0.86 mol H2/mol glycerol and 0.75 mol
      ethanol/mole glycerol. 

PMID- 25970751
TI  - Consumption of bilberries controls gingival inflammation.
AB  - Bioactive molecules in berries may be helpful in reducing the risk of oral
      diseases. The aim of this study was to determine the effect of bilberry
      consumption on the outcome of a routine dental clinical parameter of
      inflammation, bleeding on probing (BOP), as well as the impact on selected
      biomarkers of inflammation, such as cytokines, in gingival crevicular fluid (GCF)
      in individuals with gingivitis. Study individuals who did not receive standard of
      care treatment were allocated to either a placebo group or to groups that
      consumed either 250 or 500 g bilberries daily over seven days. The placebo group
      consumed an inactive product (starch). A study group, receiving standard of care
      (debridement only) was also included to provide a reference to standard of care
      treatment outcome. Cytokine levels were assayed using the Luminex MagPix system.
      The mean reduction in BOP before and after consumption of test product over 1
      week was 41% and 59% in the groups that consumed either 250 or 500 g of
      bilberries/day respectively, and was 31% in the placebo group, and 58% in the
      standard of care reference group. The analysis only showed a significant
      reduction in cytokine levels in the group that consumed 500 g of bilberries/day.
      A statistically significant reduction was observed for IL-1b (p=0.025), IL-6
      (p=0.012) and VEGF (p=0.017) in GCF samples in the group that consumed 500 g of
      bilberries daily. It appears that berry intake has an ameliorating effect on some
      markers of gingival inflammation reducing gingivitis to a similar extent compared
      to standard of care.

PMID- 25970752
TI  - Skeletal muscle mitochondrial energetic efficiency and aging.
AB  - Aging is associated with a progressive loss of maximal cell functionality, and
      mitochondria are considered a key factor in aging process, since they determine
      the ATP availability in the cells. Mitochondrial performance during aging in
      skeletal muscle is reported to be either decreased or unchanged. This
      heterogeneity of results could partly be due to the method used to assess
      mitochondrial performance. In addition, in skeletal muscle the mitochondrial
      population is heterogeneous, composed of subsarcolemmal and intermyofibrillar
      mitochondria. Therefore, the purpose of the present review is to summarize the
      results obtained on the functionality of the above mitochondrial populations
      during aging, taking into account that the mitochondrial performance depends on
      organelle number, organelle activity, and energetic efficiency of the
      mitochondrial machinery in synthesizing ATP from the oxidation of fuels. 

PMID- 25970754
TI  - Avoiding the pressure.

PMID- 25970753
TI  - Identification of MicroRNA for Intermuscular Bone Development in Blunt Snout
      Bream (Megalobrama amblycephala).
AB  - Intermuscular bone (IB), which occurs only in the myosepta of the lower teleosts,
      is attracting more attention of researchers due to its particular development and
      lack of genetic information. MicroRNAs (miRNAs) are emerging as important
      regulators for biological processes. In the present study, miRNAs from IBs and
      connective tissue (CT; encircled IBs) from six-month-old Megalobrama amblycephala
      were characterized and compared. The results revealed the sequences and
      expression levels of 218 known miRNA genes (belonging to 97 families). Of these
      miRNAs, 44 known microRNA sequences exhibited significant expression differences
      between the two libraries, with 24 and 20 differentially-expressed miRNAs
      exhibiting higher expression in the CT and IBs libraries, respectively. The
      expressions of 11 miRNAs were selected to validate in nine tissues. Among the
      high-ranked predicted gene targets, differentiation, cell cycle, metabolism,
      signal transduction and transcriptional regulation were implicated. The pathway
      analysis of differentially-expressed miRNAs indicated that they were abundantly
      involved in regulating the development and differentiation of IBs and CT. This
      study characterized the miRNA for IBs of teleosts for the first time, which
      provides an opportunity for further understanding of miRNA function in the
      regulation of IB development. 

PMID- 25970755
TI  - Economic aspects of biofilm-based wound care in diabetic foot ulcers.
AB  - OBJECTIVE: There has been a dramatic rise in the number of chronic wounds
      globally, which is placing an increased demand on decreasing health-care
      resources. With significant cuts in health-care budgets, wound care, providers
      will have to achieve better outcomes quicker and with fewer resources. By using
      new molecular methods to fully identify wound microbiota, commercially available
      antimicrobials can be used more efficiently, thereby improving outcomes and
      decreasing cost. METHOD: This study is a retrospective analysis of patients
      treated for diabetic foot ulcers (DFU); one group healed DFUs in 2005, the other
      in 2013. The 2005 patients were treated with standard of care methods common
      today. The second cohort from 2013 included patients treated using biofilm-based
      wound management anchored by molecular diagnostics. DNA methods were used to
      identify individual wound microbiota. Then personalised gels with commercially
      available antibiotics were applied topically to manage the microorganisms
      identified. RESULTS: For the 2013 cohort, total charges per patient for the
      entire course of treatment was $4,756 (total payments $3,060; L1,987). For the
      2005 cohort, each patient required treatments that culminated in total charges of
      $14,690 (total payments $11,444; L7,429). The economic difference per patient
      from 2013 compared to 2005 was a reduction in total charges of 68% (reduction in
      total reimbursement of 73%). CONCLUSION: In conjunction with other cohort
      analysis we previously reported, we feel this economic data demonstrates the
      benefits not only in wounds healed faster but also more wounds healed at a
      greatly reduced total cost.

PMID- 25970756
TI  - Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A
      pilot study.
AB  - OBJECTIVE: In the age of multiresistant microbes and the increasing lack of
      efficient antibiotics, conventional antiseptics play a critical role in the
      prevention and therapy of wound infections. Recent studies have demonstrated the
      antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot,
      study we investigate the overall suitability of one of the first APP sources for
      wound treatment focusing on its potential antimicrobial effects. METHOD: The
      wound closure rate and the bacterial colonisation of the wounds were
      investigated. Patients suffering from chronic leg ulcers were treated in a
      clinical controlled monocentric trial with either APP or octenidine (OCT). In
      patients who presented with more than one ulceration in different locations, one
      was treated with APP and the other one with OCT. Each group was treated three
      times a week over a period of two weeks. The antimicrobial efficacy was evaluated
      immediately after and following two weeks of treatment. RESULTS: Wounds treated
      with OCT showed a significantly higher microbial reduction (64%) compared to
      wounds treated with APP (47%) immediately after the treatment. Over two weeks of
      antiseptic treatment the bacterial density was reduced within the OCT group (
      35%) compared to a slight increase in bacterial density in the APP-treated group
      (+12%). Clinically, there were no signs of delayed wound healing observed in
      either group and both treatments were well tolerated. CONCLUSION: The immediate
      antimicrobial effects of the APP prototype source were almost comparable to OCT
      without any signs of cytotoxicity. This pilot study is limited by current
      configurations of the plasma source, where the narrow plasma beam made it
      difficult to cover larger wound surface areas and in order to avoid untreated
      areas of the wound bed, smaller wounds were assigned to the APP-treatment group.
      This limits the significance of AAP-related effects on the wound healing
      dynamics, as smaller wounds tend to heal faster than larger wounds. However,
      clinical wound healing studies on a larger scale now seem justifiable. A more
      advanced plasma source prototype allowing the treatment of larger wounds will
      address APP's influence on healing dynamics, synergetic treatment with current
      antiseptics and effects on multiresistant bacteria.

PMID- 25970757
TI  - Effect of superabsorbent dressings in a 3D acellular tissue model of Pseudomonas
      aeruginosa biofilm.
AB  - OBJECTIVE: To compare a superabsorbent polymer dressing (DryMax Extra; DME), an
      antibacterial absorbent polymer dressing (Sorbact absorption dressing; SB) and an
      antibacterial superabsorbent polymer dressing (Sorbion Sachet S; SSS) activity
      against Pseudomonas aeruginosa biofilms. METHOD: A 3D acellular synthetic soft
      tissue (ASST) allowing biofilm formation, was prepared and inoculated with
      Pseudomonas aeruginosa, before the application of dressings. The dressings DME,
      with and without a silver net, and two benchmark dressings SB and SSS were
      tested. After 24 hours' incubation, qualitative assessment by visual screening of
      the soft tissue and bacterial burden assessment in the dressings and acellular
      soft tissue model were performed. RESULTS: DME combined with a silver net gave a
      distinct and wide colourless zone of inhibition while partial zones of inhibition
      were seen for DME, SSS and SB. Compared with the tissues exposed to the other
      dressings, those exposed to SB and the bacterial control appeared green and
      opaque. In descending order, the most visual growth was seen in bacterial
      control, followed by SB, SSS, and DME. The bacterial load was equivalent for all
      dressings without an antimicrobial substance in both ASST (around log 10) and
      dressing (around log 11). The bacterial load for DME combined with a silver net,
      in comparison to DME alone was significantly reduced, with log 3.6 in dressings
      and log 4.2 in ASST. CONCLUSION: The removal of bacteria by DME was equivalent to
      SB and SSS. Furthermore, DME limited the production of the green colour,
      indicative of Pyocyanin. If extrapolated to a wound, the ability of DME to absorb
      Pseudomonas aeruginosa and limit Pyocyanin levels in the wound might lead to
      reduced virulence.

PMID- 25970758
TI  - Heterogeneity of wound outcome measures in RCTs of treatments for VLUs: a
      systematic review.
AB  - OBJECTIVE: Venous leg ulcers (VLUs) affect up to 4% of the population aged over
      65 years. Outcomes of randomised controlled trials (RCTs) in VLUs are important
      to guide clinical and resource decision making. Our objective was to identify
      what endpoints and wound bed outcomes were assessed in RCTs in VLUs; how these
      were assessed and what reference was made to validity and reliability of methods
      used. METHOD: A systematic review of all full text RCTs, published in English,
      from 1998-2013. RESULTS: Our criteria were met by 102 studies. There were 78
      different endpoints recorded, the majority (n=34) related to healing and were
      evaluated at 12 different times points. Size was the most frequently reported
      outcome measure (n=99), with photographs, tissue type, exudate, odour and pain
      also recorded. There was poor reporting of methods used to assess outcomes.
      Visual analogue scales predominated as a method of assessment, but 95% of studies
      made no reference to the validity or reliability of assessment methods.
      CONCLUSION: Future research in VLUs requires standards for measuring outcomes
      with acceptable inter-rater reliability and validated measures of patient
      reported outcomes.

PMID- 25970759
TI  - Expected outcomes from topical haemoglobin spray in non-healing and worsening
      venous leg ulcers.
AB  - OBJECTIVE: To evaluate the effect of topical haemoglobin spray on treatment
      response and wound-closure rates in patients with chronic venous leg ulcers.
      METHOD: A linear regression model was used to forecast healing outcomes over a 12
      month period. Simulated data were taken from normal distributions based on post
      hoc analysis of a 72-patient study in non-healing and worsening wounds (36
      patients receiving standard care and 36 receiving standard care plus topical
      haemoglobin spray). Using a simulated 25,000 'patients' from each group, the
      proportion of wound closure over time was projected. RESULTS: Simulation results
      predicted a 55% wound closure rate at six months in the haemoglobin group,
      compared with 4% in the standard care group. Over a 12-month simulation period, a
      43% overall reduction in wound burden was predicted. With the haemoglobin spray,
      85% of wounds were expected to heal in 12 months, compared with 13% in the
      standard care group. CONCLUSION: Topical haemoglobin spray promises a more
      effective treatment for chronic venous leg ulcers than standard care alone in
      wounds that are non-healing or worsening. Further research is required to
      validate these predictions and to identify achievable outcomes in other chronic
      wound types.

PMID- 25970760
TI  - Pressure ulcer risk assessment: do we need a golden hour?

PMID- 25970761
TI  - Individual differences in perceptual abilities predict target visibility during
      masking.
AB  - Many studies have shown that the visual system can implicitly process a single
      stimulus under conditions of low visibility. However, it remains unknown whether
      this ability extends when viewing conditions become more difficult, and whether
      differences in early perceptual abilities modulate masking sensitivity. To
      address these issues, participants enumerated a variable number of target
      elements among distracters in two electroencephalography experiments. Either one
      (Experiment 1) or all targets (Experiment 2) were masked through object
      substitution. Results showed that an event-related potential measure of selective
      individuation, the N2pc component, was modulated by target numerosity in both
      masked and unmasked trials, suggesting that multiple object individuation can
      operate in conditions of limited visibility. However, this effect was present
      mainly for participants with low masking effects, who overall showed more
      pronounced N2pc modulations as a function of target numerosity. Finally,
      oscillatory activity analyses revealed that early segmentation mechanisms, as
      reflected by lateralized gamma synchronization, were more active in participants
      with low sensitivity to masking, suggesting that individual variation in early
      perceptual functions is associated with susceptibility to masking such that more
      efficient segmentation and individuation mechanisms reduce the effects of
      masking. These findings cast doubt on the claim that effectively masked stimuli
      can be individuated. 

PMID- 25970762
TI  - SAFETY, BIODISTRIBUTION, AND EFFICACY OF AN AAV-5 VECTOR ENCODING HUMAN
      INTERFERON-BETA (ART-I02) DELIVERED VIA INTRA-ARTICULAR INJECTION IN RHESUS
      MONKEYS WITH COLLAGEN-INDUCED ARTHRITIS.
AB  - Preclinical studies to assess biodistribution, safety, and initial efficacy of
      ART-I02, an adeno-associated type 5 (rAAV5) vector expressing human interferon
      beta (hIFN-beta), were performed in a total of 24 rhesus monkeys with collagen
      induced arthritis. All monkeys were naive or showed limited neutralizing antibody
      1 titers to AAV5 at the start of the study. Animals were injected with a single
      intra-articular dose of ART-I02 or placebo, consisting of 3.2x1013 vg (Dose A =
      maximum feasible dose (MFD)), 4.58x1012 vg (Dose B), or placebo in the first
      affected finger joint, the ipsilateral knee, and ankle joint at the same time
      point. Animals were monitored for clinical parameters and wellbeing with a
      maximum of 4 weeks, with the option that the severity of arthritis could
      necessitate an earlier time point of sacrifice. No adverse events were noted
      after injection of ART-I02. No abnormalities were observed after histological
      evaluation of all organs. At both dose levels, immunohistochemical staining
      indicated expression of hIFN-beta. In animals injected with Dose A, we observed
      stabilisation or a reduction in swelling in the finger joint in which vector was
      administered. The highest copy numbers of vector DNA were detected in synovial
      tissue of the injected joint and the draining lymph node of the injected knee.
      High titers of Nab to rAAV5 were observed at the end of the study. Five monkeys
      developed an rAAV5-specific T cell response. Two monkeys developed Nab to hIFN
      beta. In conclusion, intra-articular injection of ART-I02 was well-tolerated and
      did not induce adverse events. After administration of Dose A of ART-I02, we
      observed a beneficial effect on joint swelling, substantiated by decreased
      histological inflammation and bone erosion scores. A GMP vector for clinical
      application has been manufactured and is currently being tested in GLP rodent
      studies, with the aim to move forward to a clinical trial.

PMID- 25970763
TI  - A theoretical investigation of mixing thermodynamics, age-hardening potential,
      and electronic structure of ternary M(1)1-x M(2)xB2 alloys with AlB2 type
      structure.
AB  - Transition metal diborides are ceramic materials with potential applications as
      hard protective thin films and electrical contact materials. We investigate the
      possibility to obtain age hardening through isostructural clustering, including
      spinodal decomposition, or ordering-induced precipitation in ternary diboride
      alloys. By means of first-principles mixing thermodynamics calculations, 45
      ternary M(1)1-x M(2)xB2 alloys comprising M(i)B2 (M(i) = Mg, Al, Sc, Y, Ti, Zr,
      Hf, V, Nb, Ta) with AlB2 type structure are studied. In particular Al1-xTixB2 is
      found to be of interest for coherent isostructural decomposition with a strong
      driving force for phase separation, while having almost concentration independent
      a and c lattice parameters. The results are explained by revealing the nature of
      the electronic structure in these alloys, and in particular, the origin of the
      pseudogap at EF in TiB2, ZrB2, and HfB2.

PMID- 25970764
TI  - Mechanical Control of Graphene on Engineered Pyramidal Strain Arrays.
AB  - Strain can tune desirable electronic behavior in graphene, but there has been
      limited progress in controlling strain in graphene devices. In this paper, we
      study the mechanical response of graphene on substrates patterned with arrays of
      mesoscale pyramids. Using atomic force microscopy, we demonstrate that the
      morphology of graphene can be controlled from conformal to suspended depending on
      the arrangement of pyramids and the aspect ratio of the array. Nonuniform strains
      in graphene suspended across pyramids are revealed by Raman spectroscopy and
      supported by atomistic modeling, which also indicates strong pseudomagnetic
      fields in the graphene. Our results suggest that incorporating mesoscale pyramids
      in graphene devices is a viable route to achieving strain-engineering of
      graphene. 

PMID- 25970765
TI  - Regulator of dendritic cell migration, ASAP1 is associated with increased
      susceptibility to tuberculosis.
AB  - Susceptibility to tuberculosis is associated with variants in the ASAP1 gene
      encoding a regulator of dendritic cell migration Curtis J et al. (2015) Nature
      Genetics 47(5):523-527. 

PMID- 25970766
TI  - Characterization of an inducible C2 H2 -type zinc finger transcription factor
      VuSTOP1 in rice bean (Vigna umbellata) reveals differential regulation between
      low pH and aluminum tolerance mechanisms.
AB  - The rice bean (Vigna umbellata) root apex specifically secretes citrate through
      expression activation of Vigna umbellata Multidrug and Toxic Compound Extrusion 1
      (VuMATE1) under aluminum (Al(3+) ) stress. However, the underlying mechanisms
      regulating VuMATE1 expression remain unknown. We isolated and characterized a
      gene encoding Sensitive to Proton Rhizotoxicity1 (STOP1)-like protein, VuSTOP1,
      from rice bean. The role of VuSTOP1 in regulating VuMATE1 expression was
      investigated using the yeast one-hybrid assay. We characterized the function of
      VuSTOP1 in Al(3)  (+)  - and H(+) -tolerance using in planta complementation
      assays. We demonstrated that VuSTOP1 has transactivation potential. We found that
      VuSTOP1 expression is inducible by Al(3+) and H(+) stress. However, although
      VuSTOP1 binds to the promoter of VuMATE1, the inconsistent tissue localization
      patterns of VuSTOP1 and VuMATE1 preclude VuSTOP1 as the major factor regulating
      VuMATE1 expression. In addition, when a protein translation inhibitor increased
      expression of VuSTOP1, VuMATE1 expression was inhibited. In planta
      complementation assay demonstrated that VuSTOP1 could fully restore expression of
      genes involved in H(+) tolerance, but could only partially restore expression of
      AtMATE. We conclude that VuSTOP1 plays a major role in H(+) tolerance, but only a
      minor role in Al(3+) tolerance. The differential transcriptional regulation of
      VuSTOP1 and VuMATE1 reveals a complex regulatory system controlling VuMATE1
      expression. 

PMID- 25970767
TI  - Short-latency crossed responses in the human biceps femoris muscle.
AB  - KEY POINTS: The present study is the first to show short-latency crossed-spinal
      reflexes in the human upper leg muscles following mechanical rotations to the
      ipsilateral knee (iKnee) joint. The short-latency reflex in the contralateral
      biceps femoris (cBF) was inhibitory following iKnee extension perturbations, and
      facilitatory following iKnee flexion perturbations. The onset latency was 44 ms,
      indicating that purely spinal pathways mediate the cBF reflexes. The short
      latency cBF inhibitory and facilitatory reflexes followed the automatic gain
      control principle, becoming larger as the level of background contraction in the
      cBF increased. The short-latency cBF reflexes were observed at the motor unit
      level using i.m. electromyography recordings, and the same population of cBF
      motor units that was inhibited following iKnee extensions was facilitated
      following iKnee flexions. Parallel interneuronal pathways from ipsilateral
      afferents to common motoneurons in the contralateral leg can therefore probably
      explain the perturbation direction-dependent reversal in the sign of the short
      latency cBF reflex. ABSTRACT: Interlimb reflexes contribute to the central neural
      co-ordination between different limbs in both humans and animals. Although
      commissural interneurons have only been directly identified in animals, spinally
      mediated interlimb reflexes have been discovered in a number of human lower limb
      muscles, indicating their existence in humans. The present study aimed to
      investigate whether short-latency crossed-spinal reflexes are present in the
      contralateral biceps femoris (cBF) muscle following ipsilateral knee (iKnee)
      joint rotations during a sitting task, where participants maintained a slight pre
      contraction in the cBF. Following iKnee extension joint rotations, an inhibitory
      reflex was observed in the surface electromyographic (EMG) activity of the cBF,
      whereas a facilitatory reflex was observed in the cBF following iKnee flexion
      joint rotations. The onset latency of both cBF reflexes was 44 ms, which is too
      fast for a transcortical pathway to contribute. The cBF inhibitory and
      facilitatory reflexes followed the automatic gain control principle, with the
      size of the response increasing as the level of background pre-contraction in the
      cBF muscle increased. In addition to the surface EMG, both short-latency
      inhibitory and facilitatory cBF reflexes were recorded directly at the motor unit
      level by i.m. EMG, and the same population of cBF motor units that were inhibited
      following iKnee extension joint rotations were facilitated following iKnee
      flexion joint rotations. Therefore, parallel interneuronal pathways (probably
      involving commissural interneurons) from ipsilateral afferents to common
      motoneurons in the contralateral leg can probably explain the perturbation
      direction-dependent reversal in the sign of the short-latency cBF reflex.

PMID- 25970768
TI  - Compact, Programmable, and Stable Biofunctionalized Upconversion Nanoparticles
      Prepared through Peptide-Mediated Phase Transfer for High-Sensitive Protease
      Sensing and in Vivo Apoptosis Imaging.
AB  - Protease represents an important class of biomarkers for disease diagnostics and
      drug screening. Conventional fluorescence-based probes for in vivo protease
      imaging suffer from short excitation wavelengths and poor photostability.
      Upconversion nanoparticles (UCNPs) hold great promise for biosensing and
      bioimaging because of their deep-tissue excitability, robust photostability, and
      minimal imaging background. However, producing highly stable and compact
      biofunctionalized UCNP probes with optimal bioresponsivity for in vivo imaging of
      protease activities still remains challenging and has not been previously
      demonstrated. Herein, we report facile preparation of highly compact and stable
      biofunctionalized UCNPs through peptide-mediated phase transfer for high
      sensitive detection of protease in vitro and in vivo. We demonstrate that the
      polyhistidine-containing chimeric peptides could displace oleic acid molecules
      capped on UCNPs synthesized in organic solvents and, thereby, directly transfer
      UCNPs from the chloroform phase to the water phase. The resulting UCNPs possess
      high stability, programmable surface properties, and a compact coating layer with
      minimized thickness for efficient luminescence resonance energy transfer (LRET).
      On the basis of this strategy, we prepared LRET-based UCNP probes with optimal
      bioresponsivity for in vitro high-sensitive detection of trypsin and in vivo
      imaging of apoptosis for chemotherapy efficacy evaluation. The reported strategy
      could be extended to construct a variety of peptide-functionalized UCNPs for
      various biomedical applications. 

PMID- 25970769
TI  - Observations of Tunable Resistive Pulse Sensing for Exosome Analysis: Improving
      System Sensitivity and Stability.
AB  - Size distribution and concentration measurements of exosomes are essential when
      investigating their cellular function and uptake. Recently, a particle size
      distribution and concentration measurement platform known as tunable resistive
      pulse sensing (TRPS) has seen increased use for the characterization of exosome
      samples. TRPS measures the brief increase in electrical resistance (a resistive
      pulse) produced by individual submicrometer/nanoscale particles as they
      translocate through a size-tunable submicrometer/micrometer-sized pore, embedded
      in an elastic membrane. Unfortunately, TRPS measurements are susceptible to
      issues surrounding system stability, where the pore can become blocked by
      particles, and sensitivity issues, where particles are too small to be detected
      against the background noise of the system. Herein, we provide a comprehensive
      analysis of the parameters involved in TRPS exosome measurements and demonstrate
      the ability to improve system sensitivity and stability by the optimization of
      system parameters. We also provide the first analysis of system noise,
      sensitivity cutoff limits, and accuracy with respect to exosome measurements and
      offer an explicit definition of system sensitivity that indicates the smallest
      particle diameter that can be detected within the noise of the trans-membrane
      current. A comparison of exosome size measurements from both TRPS and cryo
      electron microscopy is also provided, finding that a significant number of
      smaller exosomes fell below the detection limit of the TRPS platform and offering
      one potential insight as to why there is such large variability in the exosome
      size distribution reported in the literature. We believe the observations
      reported here may assist others in improving TRPS measurements for exosome
      samples and other submicrometer biological and nonbiological particles. 

PMID- 25970770
TI  - Early maternal alcohol consumption alters hippocampal DNA methylation, gene
      expression and volume in a mouse model.
AB  - The adverse effects of alcohol consumption during pregnancy are known, but the
      molecular events that lead to the phenotypic characteristics are unclear. To
      unravel the molecular mechanisms, we have used a mouse model of gestational
      ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v)
      ethanol for the first 8 days of gestation (GD 0.5-8.5). Early neurulation takes
      place by the end of this period, which is equivalent to the developmental stage
      early in the fourth week post-fertilization in human. During this exposure
      period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable
      to the effects of environmental factors. Thus, we hypothesize that early ethanol
      exposure disrupts the epigenetic reprogramming of the embryo, which leads to
      alterations in gene regulation and life-long changes in brain structure and
      function. Genome-wide analysis of gene expression in the mouse hippocampus
      revealed altered expression of 23 genes and three miRNAs in ethanol-exposed,
      adolescent offspring at postnatal day (P) 28. We confirmed this result by using
      two other tissues, where three candidate genes are known to express actively.
      Interestingly, we found a similar trend of upregulated gene expression in bone
      marrow and main olfactory epithelium. In addition, we observed altered DNA
      methylation in the CpG islands upstream of the candidate genes in the
      hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol
      exposed adult offspring (P60): we detected ethanol-induced enlargement of the
      left hippocampus and decreased volume of the left olfactory bulb. Our study
      indicates that ethanol exposure in early gestation can cause changes in DNA
      methylation, gene expression, and brain structure of offspring. Furthermore, the
      results support our hypothesis of early epigenetic origin of alcohol-induced
      disorders: changes in gene regulation may have already taken place in embryonic
      stem cells and therefore can be seen in different tissue types later in life. 

PMID- 25970771
TI  - Loss of the deubiquitylase BAP1 alters class I histone deacetylase expression and
      sensitivity of mesothelioma cells to HDAC inhibitors.
AB  - Histone deacetylases are important targets for cancer therapeutics, but their
      regulation is poorly understood. Our data show coordinated transcription of HDAC1
      and HDAC2 in lung cancer cell lines, but suggest HDAC2 protein expression is cell
      context specific. Through an unbiased siRNA screen we found that BRCA1-associated
      protein 1 (BAP1) regulates their expression, with HDAC2 reduced and HDAC1
      increased in BAP1 depleted cells. BAP1 loss-of-function is increasingly reported
      in cancers including thoracic malignancies, with frequent mutation in malignant
      pleural mesothelioma. Endogenous HDAC2 directly correlates with BAP1 across a
      panel of lung cancer cell lines, and is downregulated in mesothelioma cell lines
      with genetic BAP1 inactivation. We find that BAP1 regulates HDAC2 by increasing
      transcript abundance, rather than opposing its ubiquitylation. Importantly,
      although total cellular HDAC activity is unaffected by transient depletion of
      HDAC2 or of BAP1 due to HDAC1 compensation, this isoenzyme imbalance sensitizes
      MSTO-211H cells to HDAC inhibitors. However, other established mesothelioma cell
      lines with low endogenous HDAC2 have adapted to become more resistant to HDAC
      inhibition. Our work establishes a mechanism by which BAP1 loss alters
      sensitivity of cancer cells to HDAC inhibitors. Assessment of BAP1 and HDAC
      expression may ultimately help identify patients likely to respond to HDAC
      inhibitors. 

PMID- 25970772
TI  - The interplay between TEAD4 and KLF5 promotes breast cancer partially through
      inhibiting the transcription of p27Kip1.
AB  - Growing evidence suggests that YAP/TAZ are mediators of the Hippo pathway and
      promote breast cancer. However, the roles of YAP/TAZ transcription factor
      partners TEADs in breast cancer remain unclear. Here we found that TEAD4 was
      expressed in breast cancer cell lines, especially in triple negative breast
      cancers (TNBC) cell lines. TEAD4 binds to KLF5. Knockdown of either TEAD4 or KLF5
      in HCC1937 and HCC1806 cells induced the expression of CDK inhibitor p27.
      Depletion of either TEAD4 or KLF5 activated the p27 gene promoter and increased
      the p27 mRNA levels. Depletion of p27 partially prevents growth inhibition caused
      by TEAD4 and KLF5 knockdown. TEAD4 overexpression stimulated proliferation in
      vitro and tumor growth in mice, while stable knockdown of TEAD4 inhibited
      proliferation in vitro and tumor growth in mice. Thus TEAD4 and KLF5, in
      collaboration, promoted TNBC cell proliferation and tumor growth in part by
      inhibiting p27 gene transcription. TEAD4 is a potential target and biomarker for
      the development of novel therapeutics for breast cancer.

PMID- 25970773
TI  - Increased expression of fatty acid synthase provides a survival advantage to
      colorectal cancer cells via upregulation of cellular respiration.
AB  - Fatty acid synthase (FASN), a lipogenic enzyme, is upregulated in colorectal
      cancer (CRC). Increased de novo lipid synthesis is thought to be a metabolic
      adaptation of cancer cells that promotes survival and metastasis; however, the
      mechanisms for this phenomenon are not fully understood. We show that FASN plays
      a role in regulation of energy homeostasis by enhancing cellular respiration in
      CRC. We demonstrate that endogenously synthesized lipids fuel fatty acid
      oxidation, particularly during metabolic stress, and maintain energy homeostasis.
      Increased FASN expression is associated with a decrease in activation of energy
      sensing pathways and accumulation of lipid droplets in CRC cells and orthotopic
      CRCs. Immunohistochemical evaluation demonstrated increased expression of FASN
      and p62, a marker of autophagy inhibition, in primary CRCs and liver metastases
      compared to matched normal colonic mucosa. Our findings indicate that
      overexpression of FASN plays a crucial role in maintaining energy homeostasis in
      CRC via increased oxidation of endogenously synthesized lipids. Importantly,
      activation of fatty acid oxidation and consequent downregulation of stress
      response signaling pathways may be key adaptation mechanisms that mediate the
      effects of FASN on cancer cell survival and metastasis, providing a strong
      rationale for targeting this pathway in advanced CRC. 

PMID- 25970775
TI  - Thioredoxin reductase: a novel, independent prognostic marker in patients with
      hepatocellular carcinoma.
AB  - Here we found that hepatocellular carcinoma (HCC) patients with recurrence
      outcome and nonsurvivors had significantly increased thioredoxin reductase (TrxR)
      serum levels on reoperation (P < 0.0001 and P < 0.0001). Multivariate regression
      analysis adjusted for common risk factors showed that TrxR was an independent
      predictor of recurrence (hazard ratios [HR] = 4.19; 95% confidence intervals
      [CI]: 3.21-7.08) and overall survival (HR = 5.56; 95% CI: 3.42-10.21). The area
      under the receiver operating characteristic curve of TrxR was 0.837 (95% CI,
      0.794-0.881) for recurrence outcome and 0.901 (95% CI, 0.869-0.933) for
      mortality, which was superior to high-sensitivity-C-reactive protein and a
      fetoprotein (P < 0.001). The preoperative serum TrxR level is an independent and
      significant indicator predictive of poor prognosis and early recurrence in
      patients with HCC, which offering reliable information for predicting survival.

PMID- 25970774
TI  - Gemcitabine triggers angiogenesis-promoting molecular signals in pancreatic
      cancer cells: Therapeutic implications.
AB  - Pancreatic tumor microenvironment (TME) is characterized by poor tumor
      vasculature and extensive desmoplasia that together contribute to poor response
      to chemotherapy. It was recently shown that targeting of TME to inhibit
      desmoplasiatic reaction in a preclinical model resulted in increased microvessel
      density and intratumoral drug concentration, leading to improved therapeutic
      response. This approach, however, failed to generate a favorable response in
      clinical trial. In that regard, we have previously demonstrated a role of
      gemcitabine-induced CXCR4 signaling as a counter-defense mechanism, which also
      promoted invasiveness of pancreatic cancer (PC) cells. Here, we investigated the
      effect of gemcitabine on endothelial cell phenotype. Gemcitabine-treatment of
      human-umbilical-vein-endothelial-cells (HUVECs) did not promote the growth of
      HUVECs; however, it was induced when treated with conditioned media from
      gemcitabine-treated (Gem-CM) PC cells due to increased cell-cycle progression and
      apoptotic-resistance. Moreover, treatment of HUVECs with Gem-CM resulted in
      capillary-like structure (CLS) formation and promoted their ability to migrate
      and invade through extracellular-matrix. Gemcitabine-treatment of PC cells
      induced expression of various growth factors/cytokines, including IL-8, which
      exhibited greatest upregulation. Further, IL-8 depletion in Gem-CM diminished its
      potency to promote angiogenic phenotypes. Together, these findings suggest an
      indirect effect of gemcitabine on angiogenesis, which, in light of our previous
      observations, may hold important clinical significance. 

PMID- 25970776
TI  - Cytogenomic profiling of breast cancer brain metastases reveals potential for
      repurposing targeted therapeutics.
AB  - Breast cancer brain metastases remain a significant clinical problem.
      Chemotherapy is ineffective and a lack of treatment options result in poor
      patient outcomes. Targeted therapeutics have proven to be highly effective in
      primary breast cancer, but lack of molecular genomic characterization of
      metastatic brain tumors is hindering the development of new treatment regimens.
      Here we contribute to fill this void by reporting on gene copy number variation
      (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative
      genomic hybridization (aCGH). Results were compared to a list of cancer genes
      verified by others to influence cancer. Cancer gene aberrations were identified
      in all specimens and pathway-level analysis was applied to aggregate data, which
      identified stem cell pluripotency pathway enrichment and highlighted recurring,
      significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a
      subset of the metastatic brain tumor samples (n = 4) we compared patient-matched
      primary breast cancer specimens. The results of our CGH analysis and validation
      by alternative methods indicate that oncogenic signals driving growth of
      metastatic tumors exist in the original cancer. This report contributes support
      for more rapid development of new treatments of metastatic brain tumors, the use
      of genomic-based diagnostic tools and repurposed drug treatments. 

PMID- 25970777
TI  - c-Jun N-terminal kinase 2 prevents luminal cell commitment in normal mammary
      glands and tumors by inhibiting p53/Notch1 and breast cancer gene 1 expression.
AB  - Breast cancer is a heterogeneous disease with several subtypes carrying unique
      prognoses. Patients with differentiated luminal tumors experience better
      outcomes, while effective treatments are unavailable for poorly differentiated
      tumors, including the basal-like subtype. Mechanisms governing mammary tumor
      subtype generation could prove critical to developing better treatments. C-Jun N
      terminal kinase 2 (JNK2) is important in mammary tumorigenesis and tumor
      progression. Using a variety of mouse models, human breast cancer cell lines and
      tumor expression data, studies herein support that JNK2 inhibits cell
      differentiation in normal and cancer-derived mammary cells. JNK2 prevents
      precocious pubertal mammary development and inhibits Notch-dependent expansion of
      luminal cell populations. Likewise, JNK2 suppresses luminal populations in a p53
      competent Polyoma Middle T-antigen tumor model where jnk2 knockout causes p53
      dependent upregulation of Notch1 transcription. In a p53 knockout model, JNK2
      restricts luminal populations independently of Notch1, by suppressing Brca1
      expression and promoting epithelial to mesenchymal transition. JNK2 also inhibits
      estrogen receptor (ER) expression and confers resistance to fulvestrant, an ER
      inhibitor, while stimulating tumor progression. These data suggest that therapies
      inhibiting JNK2 in breast cancer may promote tumor differentiation, improve
      endocrine therapy response, and inhibit metastasis. 

PMID- 25970778
TI  - CEMTDD: The database for elucidating the relationships among herbs, compounds,
      targets and related diseases for Chinese ethnic minority traditional drugs.
AB  - China has different ethnic minorities that establish their own medical systems
      and practice experience for thousand years, thereafter named Chinese Ethnic
      Minority Traditional Drugs (CEMTDs) (http://www.cemtdd.com/index.html). Since
      many compounds from CEMTDs have been reported to perturb human's dysfunction
      network and restore human normal physiological conditions, the relationships
      amongst a series of compounds from specific herbs, their targets and relevant
      diseases have become our main focus in CEMTD modernization. Herein, we have
      constructed the first Chinese Ethnic Minority Traditional Drug Database (CEMTDD)
      mainly from Xinjiang Uygur Autonomous Region (XUAR), retrieving CEMTD-related
      information from different resources. CEMTDD contains about 621 herbs, 4, 060
      compounds, 2, 163 targets and 210 diseases, among which most of herbs can be
      applied into gerontology therapy including inflammation, cardiovascular disease
      and neurodegenerative disease. Gerontology is highly occurred in XUAR, and has
      abundant experience in treating such diseases, which may benefit for developing a
      new gerontology therapeutic strategy. CEMTDD displays networks for intricate
      relationships between CEMTDs and treated diseases, as well as the interrelations
      between active compounds and action targets, which may shed new light on the
      combination therapy of CEMTDs and further understanding of their herb molecular
      mechanisms for better modernized utilizations of CEMTDs, especially in
      gerontology.

PMID- 25970779
TI  - Frequent amplification of AIB1, a critical oncogene modulating major signaling
      pathways, is associated with poor survival in gastric cancer.
AB  - Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor
      coactivator (SRC) family that mediates the transcriptional activities of nuclear
      receptors and other transcription factors. It acts as a major oncogene in diverse
      cancers, whereas biological function of AIB1 in gastric cancer remains largely
      unclear. This study was designed to explore the role of AIB1 in gastric
      tumorigenesis and its potential as a useful prognostic marker and therapeutic
      target in this cancer. Our data demonstrated that AIB1 was significantly up
      regulated in gastric cancer tissues as compared with control subjects. Moreover,
      AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not
      in control subjects. AIB1 amplification was positively associated with its
      protein expression, and was significantly correlated with poor patient survival.
      AIB1 knockdown in gastric cancer cells dramatically inhibited cell proliferation,
      invasiveness and tumorigenic potential in nude mice, and induced cell cycle
      arrest and apoptosis. Mechanically, AIB1 promotes gastric cancer cell
      proliferation, survival and invasiveness through modulating major signaling
      pathways such as ErbB and Wnt/beta-catenin pathways. Collectively, these findings
      suggest that AIB1 plays an important role in the pathogenesis of gastric cancer
      and represents a potential prognostic marker and therapeutic target for this
      cancer. 

PMID- 25970780
TI  - BCL6B expression in hepatocellular carcinoma and its efficacy in the inhibition
      of liver damage and fibrogenesis.
AB  - B cell CLL/lymphoma 6 member B (BCL6B) is expressed in many normal tissues but
      expressed at very low levels in cancer tissues. It was reported that BCL6B
      inhibits hepatocellular carcinoma (HCC) metastases, but the exact role of BCL6B
      in HCC remains to be investigated. BCL6B expression was significantly decreased
      in HCC tissues compared with paired non-cancer tissues. Low BCL6B expression in
      tumors was correlated with shorter overall survival in patients, and multivariate
      Cox regression analysis revealed that BCL6B expression was an independent
      prognostic factor for human HCC patients. Moreover, a positive correlation
      between BCL6B expression and hepatic cirrhosis was found in an analysis of HCC
      clinicopathological characteristics. BCL6B expression was increased in rat
      fibrotic liver samples in response to liver injury. BCL6B transgenic rats were
      less susceptible to hepatocellular damage, inflammation and fibrosis. In vitro
      studies demonstrated that BCL6B inhibited the activation of hepatic stellate
      cells though upregulation of hepatocyte growth factor. In addition,
      transcriptomic microarray analysis was performed to explore the mechanisms in
      which BCL6B confers protection from tumorigenesis. In conclusion, BCL6B plays a
      pivotal role as a prognostic biomarker for HCC, and the restoration of BCL6B may
      be a novel strategy as an anti-fibrogenic therapy for human HCC.

PMID- 25970781
TI  - Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1
      activity.
AB  - CCDC6 was originally identified upon rearrangement with RET in human thyroid
      papillary carcinomas generating the RET/PTC1 oncogene. We have previously
      reported that CCDC6 interacts with CREB1 and represses its transcriptional
      activity. Since the function of at least one allele of CCDC6 is lost following
      RET/PTC1 rearrangements, we aimed at the generation of mice, carrying a CCDC6
      mutant gene. Previous studies suggested that the coiled-coil domain of CCDC6,
      mainly encoded by human exon 2, is required for the protein function. Therefore,
      we engineered a murine Ccdc6 construct, carrying a deletion of the exon 2, that
      was able to exert only a mild repression on CREB1 transcriptional activity, with
      respect to the wild type Ccdc6. Subsequently, we generated Ccdc6-ex2 knock-in
      mice. These mice developed thyroid hyperplasia associated with an enhanced CREB1
      activity and an increased expression of the CREB-1 regulated genes. These results
      strongly support a CCDC6 promoting role, ascribed to its functional impairment,
      in the development of thyroid papillary carcinomas harboring the RET/PTC1
      oncogene.

PMID- 25970782
TI  - RNA sequencing reveals differentially expressed genes as potential diagnostic and
      prognostic indicators of gallbladder carcinoma.
AB  - Gallbladder carcinoma (GBC) is a rare tumor with a dismal survival rate overall.
      Hence, there is an urgent need for exploring more specific and sensitive
      biomarkers for the diagnosis and treatment of GBC. At first, amplified total RNAs
      from two paired GBC tumors and adjacent non-tumorous tissues (ANTTs) were
      subjected to RNA sequencing. 161 genes were identified differentially expressed
      between tumors and ANTTs. Functional enrichment analysis indicated that the up
      regulated genes in tumor were primarily associated with signaling molecules and
      enzyme modulators, and mainly involved in cell cycles and pathways in cancer.
      Twelve differentially expressed genes (DEGs) were further confirmed in another
      independent cohort of 35 GBC patients. Expression levels of BIRC5, TK1, TNNT1 and
      MMP9 were found to be positively related to postoperative relapse. There was also
      a significant correlation between BIRC5 expression and tumor-node-metastasis
      (TNM) stage. Besides, we observed a positive correlation between serum CA19-9
      concentration and the expression levels of TNNT1, MMP9 and CLIC3. Survival
      analysis revealed that GBC patients with high TK1 and MMP9 expression levels had
      worse prognosis. These identified DEGs might not only be promising biomarkers for
      GBC diagnosis and prognosis, but also expedite the discovery of novel therapeutic
      strategies.

PMID- 25970783
TI  - New dimension in therapeutic targeting of BCL-2 family proteins.
AB  - Proteins of the BCL-2 family control the mitochondrial pathway of apoptosis.
      Targeting these proteins proves to be an attractive strategy for anticancer
      therapy. The biological context is based on the fact that BH3-only members of the
      family are specific antagonists of prosurvival members. This prompted the
      identification of "BH3 mimetic" compounds. These small peptides or organic
      molecules indeed mimic the BH3 domain of BH3-only proteins: by selectively
      binding and antagonizing prosurvival proteins, they can induce apoptosis in
      malignant cells. Some small-molecule inhibitors of prosurvival proteins have
      already entered clinical trials in cancer patients and two of them have shown
      significant therapeutic effects. The latest developments in the field of
      targeting BCL-2 family proteins highlight several new antagonists of prosurvival
      proteins as well as direct activators of proapoptotic proteins. These compounds
      open up novel prospects for the development of BH3 mimetic anticancer drugs. 

PMID- 25970784
TI  - PTPRG suppresses tumor growth and invasion via inhibition of Akt signaling in
      nasopharyngeal carcinoma.
AB  - Protein Tyrosine Phosphatase, Receptor Type G (PTPRG) was identified as a
      candidate tumor suppressor gene in nasopharyngeal carcinoma (NPC). PTPRG induces
      significant in vivo tumor suppression in NPC. We identified EGFR as a PTPRG
      potential interacting partner and examined this interaction. Dephosphorylation of
      EGFR at EGFR-Y1068 and -Y1086 sites inactivated the PI3K/Akt signaling cascade
      and subsequent down-regulation of downstream pro-angiogenic and -invasive
      proteins (VEGF, IL6, and IL8) and suppressed tumor cell proliferation,
      angiogenesis, and invasion. The effect of Akt inhibition in NPC cells was further
      validated by Akt knockdown experiments in the PTPRG-down-regulated NPC cell
      lines. Our results suggested that inhibition of Akt in NPC cells induces tumor
      suppression at both the in vitro and in vivo levels, and also importantly, in
      vivo metastasis. In conclusion, we confirmed the vital role of PTPRG in
      inhibiting Akt signaling with the resultant suppression of in vivo tumorigenesis
      and metastasis. 

PMID- 25970785
TI  - Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF
      beta/SMAD signaling.
AB  - Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype
      associated with a poor prognosis. The mechanism involved in TNBC progression
      remains largely unknown. To date, there are no effective therapeutic targets for
      this tumor subtype. In this study, by performing quantitative proteomic analyses
      in highly metastatic and parental breast cancer cell line, we found that RAB1B, a
      member of the RAS oncogene family, was significantly down-regulated in highly
      metastatic breast cancer cells. Moreover, down-regulation of RAB1B was also found
      to promote the proliferation and migration of TNBC cells in vitro and in vivo.
      Mechanistically, loss of RAB1B resulted in elevated expression of TGF-beta
      receptor 1 (TbetaR1) through decreased degradation of ubiquitin, increased levels
      of phosphorylated SMAD3 and TGF-beta-induced epithelial-mesenchymal transition
      (EMT). Furthermore, low RAB1B expression correlated with poor prognosis in breast
      cancer patients. Taken together, our findings reveal that RAB1B acts as a
      metastasis suppressor in TNBC by regulating the TGF-beta/SMAD signaling pathway
      and RAB1B may serve as a novel biomarker of prognosis and the response to anti
      tumor therapeutics for patients with TNBC.

PMID- 25970786
TI  - Regulation of VCP/p97 demonstrates the critical balance between cell death and
      epithelial-mesenchymal transition (EMT) downstream of ER stress.
AB  - Valosin-containing protein (VCP), also called p97, is a AAA+ ATPase that has been
      shown to be involved in endoplasmic reticulum-associated protein degradation
      (ERAD), mitochondria quality control and vesicle transport. We and others have
      previously found that disruption of VCP is sufficient to cause endoplasmic
      reticulum (ER) stress. We observed that induction of ER stress either following
      siRNA mediated loss of VCP or inhibition of VCP with eeyarestatin I potently
      activates an EMT-like state in cells. Interestingly, both ER stress and EMT are
      reversible events. Further, brief treatment of cells with eeyarestatin I
      increases EMT markers, and migratory and invasive properties of lung cancer
      cells. By examining primary lung adenocarcinoma patient samples we find that the
      VCP locus is heterozygously lost in nearly half of lung adenocarcinomas and VCP
      protein expression is decreased in nearly all primary lung tumors. Further,
      primary lung adenocarcinomas have increased ER stress and EMT markers. These
      observations have potential clinical relevance because increased ER stress and
      EMT markers are known to contribute to chemoresistance and poor survival of
      patients with lung adenocarcinoma.

PMID- 25970789
TI  - Proteomic profiling of high risk medulloblastoma reveals functional biology.
AB  - Genomic characterization of medulloblastoma has improved molecular risk
      classification but struggles to define functional biological processes,
      particularly for the most aggressive subgroups. We present here a novel proteomic
      approach to this problem using a reference library of stable isotope labeled
      medulloblastoma-specific proteins as a spike-in standard for accurate
      quantification of the tumor proteome. Utilizing high-resolution mass
      spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells
      and demonstrate that high-risk MYC amplified tumors can be segregated based on
      protein expression patterns. We cross-validated the differentially expressed
      protein candidates using an independent transcriptomic data set and further
      confirmed them in a separate cohort of medulloblastoma tissue samples to identify
      the most robust proteogenomic differences. Interestingly, highly expressed
      proteins associated with MYC-amplified tumors were significantly related to
      glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM)
      by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under
      hypoxic conditions, these MYC-amplified tumors demonstrated increased viability
      compared to non-amplified tumors within the same subgroup. Taken together, these
      findings highlight the power of proteomics as an integrative platform to help
      prioritize genetic and molecular drivers of cancer biology and behavior. 

PMID- 25970788
TI  - Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic
      target in undifferentiated pleomorphic sarcomas.
AB  - A common and aggressive subtype of soft-tissue sarcoma, undifferentiated
      pleomorphic sarcoma (UPS) was examined to determine the role of micro-RNAs
      (miRNAs) in modulating distant metastasis. Following histopathologic review, 110
      fresh frozen clinically annotated UPS samples were divided into two independent
      cohorts for Training (42 patients), and Validation (68 patients) analyses. Global
      miRNA profiling on the Training Set and functional analysis in vitro suggested
      that miRNA-138 and its downstream RHO-ROCK cell adhesion pathway was a convergent
      target of miRNAs associated with the development of metastasis. A six-miRNA
      signature set prognostic of distant metastasis-free survival (DMFS) was developed
      from Training Set miRNA expression values. Using the six-miRNA signature,
      patients were successfully categorized into high- and low-risk groups for DMFS in
      an independent Validation Set, with a hazard ratio (HR) of 2.25 (p = 0.048).
      After adjusting for other known prognostic variables such as age, gender, tumor
      grade, size, depth, and treatment with radiotherapy, the six-miRNA signature
      retained prognostic value with a HR of 3.46 (p < 0.001). A prognostic miRNA
      biomarker for clinical validation was thus identified along with a functional
      pathway that modulates UPS metastatic phenotype. 

PMID- 25970791
TI  - Effects of manipulated above- and belowground organic matter input on soil
      respiration in a Chinese pine plantation.
AB  - Alteration in the amount of soil organic matter input can have profound effect on
      carbon dynamics in forest soils. The objective of our research was to determine
      the response in soil respiration to above- and belowground organic matter
      manipulation in a Chinese pine (Pinus tabulaeformis) plantation. Five organic
      matter treatments were applied during a 2-year experiment: both litter removal
      and root trenching (LRRT), only litter removal (LR), control (CK), only root
      trenching (RT) and litter addition (LA). We found that either aboveground litter
      removal or root trenching decreased soil respiration. On average, soil
      respiration rate was significantly decreased in the LRRT treatment, by about
      38.93% +/- 2.01% compared to the control. Soil respiration rate in the LR
      treatment was 30.65% +/- 1.87% and in the RT treatment 17.65% +/- 1.95% lower
      than in the control. Litter addition significantly increased soil respiration
      rate by about 25.82% +/- 2.44% compared to the control. Soil temperature and soil
      moisture were the main factors affecting seasonal variation in soil respiration.
      Up to the 59.7% to 82.9% seasonal variation in soil respiration is explained by
      integrating soil temperature and soil moisture within each of the various organic
      matter treatments. The temperature sensitivity parameter, Q10, was higher in the
      RT (2.72) and LA (3.19) treatments relative to the control (2.51), but lower in
      the LRRT (1.52) and LR treatments (1.36). Our data suggest that manipulation of
      soil organic matter input can not only alter soil CO2 efflux, but also have
      profound effect on the temperature sensitivity of organic carbon decomposition in
      a temperate pine forest. 

PMID- 25970792
TI  - Prevalence and Clinical Outcome of CYP21A2 Gene Mutations in Patients with
      Nonfunctional Adrenal Incidentalomas.
AB  - Adrenal tumors, discovered incidentally in approximately 4.5% of imaging
      procedures, are known as adrenal incidentalomas. Nonclassic congenital adrenal
      hyperplasia, mild form of 21-hydroxylase deficiency, may lead to the development
      of adrenocortical tumors. The aim of the study was to evaluate prevalence of the
      most common nonclassic mutations of CYP21A2 gene in patients with adrenal
      incidentalomas and investigate possible relationship with clinical outcome. One
      hundred adult patients with such lesions were enrolled. Clinical, imaging and
      biochemical evaluation were performed to rule out hormonal overproduction or
      potential malignancy. All subjects and a control group of 100 neonates were
      genotyped for P30L, P453S, and V281L mutations of CYP21A2 gene using direct
      sequencing. Clinical and imaging features as well as hormone levels were
      analyzed. Heterozygous CYP21A2 gene mutations were detected in 8 subjects but not
      in the neonates. Thus, the risk of carrying mutant allele was significantly
      higher in subjects with adrenal tumors (OR=8.7; 95% CI=2.23-389.56; p=0.003).
      Mean concentrations of renin, basal, and stimulated 17-hydroxyprogesterone were
      higher and ACTH was lower in the carriers than in the remaining subjects.
      Furthermore, the carriers had higher incidence of hypertension (100 vs. 52.1%,
      p=0.008) and diabetes (50 vs. 11.9%, p=0.003). ACTH-stimulated 17
      hydroxyprogesterone levels varied widely among the carriers. In summary,
      prevalence of P30L, P453S, and V281L mutations of CYP21A2 gene is increased in
      patients with adrenocortical tumors. In these subjects, carrying the analyzed
      mutant alleles may increase the risk of diabetes and hypertension. ACTH
      stimulation test does not satisfactorily predict presence of heterozygous CYP21A2
      mutations in patients with adrenal tumors. 

PMID- 25970790
TI  - Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill
      cancer subtypes enriched for stem cell-like properties.
AB  - Key players in translational regulation such as ribosomes might represent
      powerful, but hitherto largely unexplored, targets to eliminate drug-refractory
      cancer stem cells (CSCs). A recent study by the Lisanti group has documented how
      puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits
      ribosomal protein translation, can efficiently suppress CSC states in
      tumorspheres and monolayer cultures. We have used a closely related approach
      based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized
      antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer
      cell lines enriched for stem cell-like properties. Antibiotics directly targeting
      active sites of the ribosome including emetine, puromycin and cycloheximide,
      inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents
      such as daunorubicin, and indirect inhibitors of protein synthesis such as
      acriflavine, had the largest cytotoxic impact against claudin-low and basal-like
      breast cancer cells. Thus, biologically aggressive, treatment-resistant breast
      cancer subtypes enriched for stem cell-like properties exhibit exacerbated
      chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting
      protein synthesis. These results suggest that old/existing microbicides might be
      repurposed not only as new cancer therapeutics, but also might provide the tools
      and molecular understanding needed to develop second-generation inhibitors of
      ribosomal translation to eradicate CSC traits in tumor tissues. 

PMID- 25970793
TI  - Collaborative studies on the development of national reference standards for
      potency determination of H7N9 influenza vaccine.
AB  - The outbreak of human infections of a novel avian influenza virus A (H7N9)
      prompted the development of the vaccines against this virus. Like all types of
      influenza vaccines, H7N9 vaccine must be tested for its potency prior to being
      used in humans. However, the unavailability of international reference reagents
      for the potency determination of H7N9 vaccines substantially hinders the progress
      in vaccine development. To facilitate clinical development, we enlisted 5
      participants in a collaborative study to develop critical reagents used in Single
      Radial Immunodiffusion (SRID), the currently acceptable assay for potency
      determination of influenza vaccine. Specifically, the hemagglutinin (HA) content
      of one vaccine bulk for influenza A (H7N9), herein designated as Primary Liquid
      Standard (PLS), was determined by SDS-PAGE. In addition, the freeze-dried antigen
      references derived from PLS were prepared to enhance the stability for long term
      storage. The final HA content of lyophilized antigen references were calibrated
      against PLS by SRID assay in a collaborative study. Importantly, application of
      these national reference standards to potency analyses greatly facilitated the
      development of H7N9 vaccines in China. 

PMID- 25970794
TI  - A randomized controlled trial of ProRoot MTA, OrthoMTA and RetroMTA for pulpotomy
      in primary molars.
AB  - OBJECTIVES: The aim of this study was to determine the clinical efficacy of the
      newly developed OrthoMTA and RetroMTA, compared to conventionally used ProRoot
      MTA, for pulpotomy in primary teeth. MATERIAL AND METHODS: In this randomized
      clinical trial, 151 molars from 102 children, who met the inclusion criteria and
      were 3-10 years old, were enrolled. Ultimately, 143 teeth were divided in a
      randomized, single-blind manner into three groups according to the planned
      treatment: RetroMTA (n = 49 teeth), OrthoMTA (n = 47 teeth) or ProRoot MTA (n =
      47 teeth). Clinical and radiographic follow-up examinations were conducted at 3,
      6 and 12 months postoperatively. RESULTS: By the end of the study period, 109
      teeth were evaluated at 12 months. The radiographic success rates in these three
      groups were 100%, 94.7% and 94.7%, respectively; the corresponding clinical
      success rates were 100%, 97.4% and 100%. The Kaplan-Meier survival function
      curves relative to clinical and radiographic cumulative survival rates did not
      differ significantly between the three groups. CONCLUSIONS: The success rates of
      RetroMTA, OrthoMTA and ProRoot MTA are indistinguishable, indicating that
      pulpotomy can be carried out successfully in primary molars with the newly
      developed materials.

PMID- 25970795
TI  - Phosphonic Acid Modification of GaInP2 Photocathodes Toward Unbiased
      Photoelectrochemical Water Splitting.
AB  - The p-type semiconductor GaInP2 has a nearly ideal bandgap (~1.83 eV) for
      hydrogen fuel generation by photoelectrochemical water splitting but is unable to
      drive this reaction because of misalignment of the semiconductor band edges with
      the water redox half reactions. Here, we show that attachment of an appropriate
      conjugated phosphonic acid to the GaInP2 electrode surface improves the band edge
      alignment, closer to the desired overlap with the water redox potentials. We
      demonstrate that this surface modification approach is able to adjust the
      energetic position of the band edges by as much as 0.8 eV, showing that it may be
      possible to engineer the energetics at the semiconductor/electrolyte interface to
      allow for unbiased water splitting with a single photoelectrode having a bandgap
      of less than 2 eV. 

PMID- 25970796
TI  - Progress testing in family medicine--A novel use for simulated office oral exams.
AB  - BACKGROUND: Simulated office orals (SOOs) are used by the College of Family
      Physicians of Canada as a method to evaluate family medicine resident readiness
      for clinical practice. The use of SOOs as a progress test would provide residency
      programs with useful information to determine resident readiness for challenging
      the certification exam. The data from a progress test could then be easily
      manipulated to generate a risk assessment plot. METHODS: During a prospective
      cohort study conducted at the University of Ottawa, the feasibility of using
      practice SOO sessions, a structured clinical exam, as a progress test was
      explored. Twenty-three residents participated in all four practice SOO sessions
      and their results were entered into a risk assessment plot. RESULTS: Repeated
      measures analysis of the data using ANOVA demonstrated that the residents' scores
      at each time point were statistically different from each other, generating an
      F(3, 66) = 27.52, p < 0.001, eta(2) = 0.55.and that the relationship over time
      was linear with an F(1, 22) = 123.80, p < 0.001, eta(2) = 0.85. At the final time
      point, a risk assessment resulted in no learners mapping to quadrants III or IV.
      CONCLUSIONS: Our results demonstrate the feasibility of utilizing a SOO exam, a
      clinical exam, as a progress test. In addition, we propose generating a risk
      assessment plot, using the data from the Fall 2013 and Spring 2014 practice SOO
      sessions, as a means of identifying residents at risk. Further studies will be
      needed to confirm the utility of this analysis. Combined with other measures
      acquired during in-training evaluation, the utilization of practice SOOs as a
      progress test will provide program directors with valuable information on
      resident progression.

PMID- 25970797
TI  - A general Pd-catalyzed alpha- and gamma-benzylation of aldehydes for the
      formation of quaternary centers.
AB  - A palladium-catalyzed benzylation of alpha-branched aldehydes has been developed
      using benzyl methyl carbonates. The method gives access to congested quaternary
      centers in the vicinity of one of the most sensitive carbonyl functionalities and
      displays unprecedented generality with respect to both coupling partners.
      Evidence for the direct involvement of a Pd-eta(3)-benzyl intermediate is
      provided. Extension of this strategy to the gamma-benzylation of alpha,beta
      unsaturated aldehydes is further demonstrated. 

PMID- 25970798
TI  - Prevalence and Predictors of Posttraumatic Stress Symptomatology Among Burn
      Survivors: A Systematic Review and Meta-Analysis.
AB  - Burns can be a traumatic and stressful experience, although each patient may
      respond in very different ways. The aim of this study was to explore the
      variability on posttraumatic stress disorder (PTSD) and acute stress disorder
      (ASD) prevalence and evaluate the specific weight of different variables on PTSD
      development among adult burn patients. A systematic review was carried out to
      explore the prevalence of ASD and PTSD and identify their predictors. Meta
      analytical methods were used to explore the strength of association between PTSD
      and the latter. From an initial pool of 190 studies, 24 were used in the
      systematic review, and only 19 studies could be used for the meta-analysis
      because of different methodological limitations. The prevalence of ASD at
      baseline ranged from 2 to 30% and prevalence of PTSD ranged from 3 to 35% at 1
      month, 2 to 40% between 3 and 6 months, 9 to 45% in the year postinjury and
      ranged 7 to 25% more than 2 years later. Life threat perception was the strongest
      predictor for PTSD occurrence, followed by acute intrusive symptoms and pain
      associated with burn injuries. Predictive variables identified in this research
      may be useful in targeting burn patients who are at risk for developing
      posttraumatic stress symptoms and stress-related psychological symptoms. 

PMID- 25970799
TI  - Mutations in HTRA2 are not a common cause of familial classic ET.

PMID- 25970800
TI  - Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis:
      Results From the Psoriasis Longitudinal Assessment and Registry (PSOLAR).
AB  - IMPORTANCE: The efficacy of treatment for psoriasis must be balanced against
      potential adverse events. OBJECTIVE: To determine the effect of treatment on the
      risk of serious infections in patients with psoriasis. DESIGN, SETTING, AND
      PARTICIPANTS: A multicenter, longitudinal, disease-based registry (Psoriasis
      Longitudinal Assessment and Registry [PSOLAR]) at dermatology centers.
      Participants were adult patients with psoriasis who were receiving or were
      eligible to receive conventional systemic or biologic agents. The registry opened
      on June 20, 2007, and data included herein were collected through August 23,
      2013. EXPOSURES: Patients were prescribed psoriasis therapies as in standard
      clinical practice. Patients will be followed for up to 8 years. Data were
      collected and serious adverse events (including serious infections) were assessed
      at regular intervals. MAIN OUTCOMES AND MEASURES: Cohort characteristics are
      described based on evaluation at entry into the registry. The cumulative
      incidence rates of serious infections are reported across treatment cohorts,
      including ustekinumab, infliximab, adalimumab, etanercept, and nonbiologics (with
      or without methotrexate). A multivariate analysis using a Cox proportional
      hazards regression model was used to identify predictors of the time to the first
      serious infection using the nonmethotrexate/nonbiologics cohort as the reference.
      RESULTS: Data were analyzed from 11,466 patients with psoriasis (22,311 patient
      years). Differences in patient characteristics were found between the biologics
      and nonmethotrexate/nonbiologics cohorts (eg, age, sex, body mass index, and
      disease characteristics), as well as among the individual biologic groups (eg, a
      higher prevalence of psoriatic arthritis in the infliximab cohort). The
      cumulative incidence rate of serious infections was 1.45 per 100 patient-years (n
      = 323) across treatment cohorts, and the rates were 0.83, 1.47, 1.97, and 2.49
      per 100 patient-years in the ustekinumab, etanercept, adalimumab, and infliximab
      cohorts, respectively, and 1.05 and 1.28 per 100 patient-years in the
      nonmethotrexate/nonbiologics and methotrexate/nonbiologics cohorts, respectively.
      The most commonly reported types of serious infections across the registry were
      pneumonia and cellulitis. Increasing age, diabetes mellitus, smoking, significant
      infection history, infliximab exposure, and adalimumab exposure were each
      associated with an increased risk of serious infection. CONCLUSIONS AND
      RELEVANCE: Results from PSOLAR suggest a higher risk of serious infections with
      adalimumab and infliximab compared with nonmethotrexate and nonbiologic
      therapies. No increased risk was observed with ustekinumab or etanercept. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00508547.

PMID- 25970802
TI  - Chitosan-based hydrogel tissue scaffolds made by 3D plotting promotes osteoblast
      proliferation and mineralization.
AB  - A 3D plotting system was used to make chitosan-based tissue scaffolds with
      interconnected pores using pure chitosan (C) and chitosan cross-linked with
      pectin (CP) and genipin (CG). A freeze-dried chitosan scaffold (CF/D) was made to
      compare with C, to observe the effects of structural differences. The fiber size,
      pore size, porosity, compression strength, swelling ratio, drug release efficacy,
      and cumulative weight loss of the scaffolds were measured. Osteoblasts were
      cultured on the scaffolds and their proliferation, type I collagen production,
      alkaline phosphatase activity, calcium deposition, and morphology were observed.
      C had a lower swelling ratio, degradation, porosity and drug release efficacy and
      a higher compressional stiffness and cell proliferation compared to CF/D (p <
      0.05). Of the 3D-plotted samples, cells on CP exhibited the highest degree of
      mineralization after 21 d (p < 0.05). CP also had the highest swelling ratio and
      fastest drug release, followed by C and CG (p < 0.05). Both CP and CG were
      stiffer and degraded more slowly in saline solution than C (p < 0.05). In
      summary, 3D-plotted scaffolds were stronger, less likely to degrade and better
      promoted osteoblast cell proliferation in vitro compared to the freeze-dried
      scaffolds. C, CP and CG were structurally similar, and the different crosslinking
      caused significant changes in their physical and biological performances.

PMID- 25970803
TI  - Understanding the crystallization behavior of as-deposited Ti-Sb-Te alloys
      through real-time radial distribution functions.
AB  - Phase change materials, successfully used in optical data-storage and non
      volatile electronic memory, are well-known for their ultrafast crystallization
      speed. However, the fundamental understanding of their crystallization behavior,
      especially the nucleation process, is limited by present experimental techniques.
      Here, real-time radial distribution functions (RDFs), derived from the selected
      area electron diffractions, are employed as structural probes to comprehensively
      study both nucleation and subsequent growth stages of Ti-doped Sb2Te3 (TST)
      materials in the electron-irradiation crystallization process. It can be found
      that the incorporation of Ti atoms in Sb2Te3 forms wrong bonds such as Ti-Te, Ti
      Sb, breaks the originally ordered atomic arrangement and diminishes the initial
      nucleus size of the as-deposited films, which results in better thermal
      stability. But these nuclei hardly grow until their sizes exceed a critical
      value, and then a rapid growth period starts. This means that an extended
      nucleation time is required to form the supercritical nuclei of TST alloys with
      higher concentration. Also, the increasing formation of four-membered rings,
      which served as nucleation sites, after doping excessive Ti is responsible for
      the change of the crystallization behavior from growth-dominated to nucleation
      dominated. 

PMID- 25970801
TI  - Reduced efficiency of sarcolipin-dependent respiration in myocytes from humans
      with severe obesity.
AB  - OBJECTIVE: Sarcolipin (SLN) regulates muscle energy expenditure through its
      action on sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump. It is unknown
      whether SLN-dependent respiration has relevance to human obesity, but whole
      transcriptome gene expression profiling revealed that SLN was more highly
      expressed in myocytes from individuals with severe obesity (OB) than in lean
      controls (LN). The purpose of this study was to examine SLN-dependent cellular
      respiratory rates in LN and OB human muscles. METHODS: Primary myocytes were
      isolated from muscle biopsy from seven LN and OB Caucasian females. Cellular
      respiration was assessed with and without lentivirus-mediated SLN knockdown in LN
      and OB myocytes. RESULTS: SLN mRNA and protein abundance was greater in OB
      compared to LN cells. Despite elevated SLN levels in wild-type OB cells,
      respiratory rates among SLN-deficient cells were higher in OB compared to LN.
      Obesity-induced reduction in efficiency of SLN-dependent respiration was
      associated with altered sarcoplasmic reticulum phospholipidome. CONCLUSIONS: SLN
      dependent respiration is reduced in muscles from humans with severe obesity
      compared to lean controls. Identification of the molecular mechanism that affects
      SLN efficiency might lead to interventions that promote an increase in skeletal
      muscle energy expenditure.

PMID- 25970804
TI  - Knowledge to action for solving complex problems: insights from a review of nine
      international cases.
AB  - INTRODUCTION: Solving complex problems such as preventing chronic diseases
      introduces unique challenges for the creation and application of knowledge, or
      knowledge to action (KTA). KTA approaches that apply principles of systems
      thinking are thought to hold promise, but practical strategies for their
      application are not well understood. In this paper we report the results of a
      scan of systems approaches to KTA with a goal to identify how to optimize their
      implementation and impact. METHODS: A 5-person advisory group purposefully
      selected 9 initiatives to achieve diversity on issues addressed and
      organizational forms. Information on each case was gathered from documents and
      through telephone interviews with primary contacts within each organization.
      Following verification of case descriptions, an inductive analysis was conducted
      within and across cases. RESULTS: The cases revealed 5 guidelines for moving from
      conceiving KTA systems to implementing them: (1) establish and nurture
      relationships, (2) co-produce and curate knowledge, (3) create feedback loops,
      (4) frame as systems interventions rather than projects, and (5) consider
      variations across time and place. CONCLUSION: Results from the environmental scan
      are a modest start to translating systems concepts for KTA into practice. Use of
      the strategies revealed in the scan may improve KTA for solving complex public
      health problems. The strategies themselves will benefit from the development of a
      science that aims to understand adaptation and ongoing learning from policy and
      practice interventions, strengthens enduring relationships, and fills system gaps
      in addition to evidence gaps. Systems approaches to KTA will also benefit from
      robust evaluations.

PMID- 25970805
TI  - Physical inactivity and television-viewing time among Aboriginal adults with
      asthma: a cross-sectional analysis of the Aboriginal Peoples Survey.
AB  - INTRODUCTION: The purpose of this analysis was to (1) determine the association
      between asthma and physical activity levels or sedentary time among Aboriginal
      adults, and (2) understand the influence of physical inactivity and sedentary
      time on health care use among Aboriginal adults with asthma. METHODS: We analyzed
      20 953 adults from the 2006 Aboriginal Peoples Survey. Those with self-reported
      physician-diagnosed asthma and a current prescription for asthma medication were
      considered to have current asthma. Insufficient physical activity was defined as
      < 3 hours/week of moderate to vigorous physical activity; high television screen
      time was defined as > 10 hours/week. Health care use was assessed using the
      number of health professional visits and overnight hospital stays. RESULTS:
      Aboriginal adults with asthma were more likely to report high television-viewing
      time (OR = 1.16; CI: 1.11-1.22) and insufficient physical activity (OR = 1.15;
      CI: 1.10-1.20) than those without asthma. Those with asthma who reported high
      television-viewing time reported more health professional consults in the past 12
      months (OR = 2.59; CI: 2.34-2.87), more overnight stays in hospital in the past
      year (OR = 1.95; CI: 1.82-2.08) and more overnight stays in the hospital in the
      past 5 years (OR = 1.13; CI: 1.07-1.18); results were less consistent for
      physical activity and health care use. CONCLUSION: These findings suggest that
      Aboriginal adults with asthma are less active than their peers without asthma and
      that such a lifestyle may be associated with higher health care use. These
      findings have implications for physical activity promotion and sedentary
      behaviour strategies targeting Aboriginal adults with asthma.

PMID- 25970806
TI  - Stressed SIRT7: facing a crossroad of senescence and immortality.
AB  - SIRT7 with coenzyme NAD catalyzes protein de-acetylation. In stress response,
      SIRT7 regulates protein folding in mitochondria with unknown mechanisms.
      Decreases in SIRT7 entrain hematopoietic stem cell senescence, but increasing
      SIRT7 causes elevation of hematopoietic stem cell regenerative function. We
      discuss the recent findings on SIRT7 and its binding proteins, NRF1 and
      GABPbeta1, in decision making between the choices of inducing cell aging and
      immortality. 

PMID- 25970807
TI  - RF-SABRE: A Way to Continuous Spin Hyperpolarization at High Magnetic Fields.
AB  - A new technique is developed that allows one to carry out the signal
      amplification by reversible exchange (SABRE) experiments at high magnetic field.
      SABRE is a hyperpolarization method, which utilizes transfer of spin order from
      para-hydrogen to the spins of a substrate in transient iridium complexes.
      Previously, it has been thought that such a transfer of spin order is only
      efficient at low magnetic fields, notably, at level anti-crossing (LAC) regions.
      Here it is demonstrated that LAC conditions can also be fulfilled at high fields
      under the action of a RF field. The high-field RF-SABRE experiment can be
      implemented using commercially available nuclear magnetic resonance (NMR) and
      magnetic resonance imaging (MRI) machines and does not require technically
      demanding field-cycling. The achievable NMR enhancements are around 100 for
      several substrates as compared to their NMR signals at thermal equilibrium
      conditions at 4.7 T. The frequency dependence of RF-SABRE is comprised of well
      pronounced peaks and dips, whose position and amplitude are conditioned solely by
      the magnetic resonance parameters such as chemical shifts and scalar coupling of
      the spin system involved in the polarization transfer and by the amplitude of the
      RF field. Thus, the proposed method can serve as a new sensitive tool for probing
      transient complexes. Simulations of the dependence of magnetization transfer
      (i.e., NMR signal amplifications) on the frequency and amplitude of the RF field
      are in good agreement with the developed theoretical approach. Furthermore, the
      method enables continuous re-hyperpolarization of the SABRE substrate over a long
      period of time, giving a straightforward way to repetitive NMR experiments. 

PMID- 25970808
TI  - Molecular template growth and its applications in organic electronics and
      optoelectronics.

PMID- 25970809
TI  - Immediate Lower Extremity Tourniquet Application to Delay Onset of Reperfusion
      Injury after Prolonged Crush Injury.
AB  - Reperfusion after severe crush injury is an infrequent, but life-threatening
      condition. It is a unique aspect of prehospital medicine that occurs in the
      presence of emergency responders attempting to extricate and treat patients who
      have suffered a crushing injury. These events are unlikely to occur in the
      hospital setting and, as a result, remain poorly studied. Some evidence exists
      regarding prophylaxis, but the efficacy of these treatments has not been clearly
      established. The use of commercial tourniquets to delay the onset of reperfusion
      injury has previously been described in theory. Extensive literature now exists
      supporting the safety of tourniquet use in limb trauma and this potential life
      saving measure requires further study in patients with crush injury. We present a
      case of prehospital tourniquet application to delay reperfusion injury after
      crush injury that resulted in a reduction in morbidity and complete limb salvage.

PMID- 25970810
TI  - Breaking a pathogen's iron will: Inhibiting siderophore production as an
      antimicrobial strategy.
AB  - The rise of antibiotic resistance is a growing public health crisis. Novel
      antimicrobials are sought, preferably developing nontraditional chemical
      scaffolds that do not inhibit standard targets such as cell wall synthesis or the
      ribosome. Iron scavenging has been proposed as a viable target, because bacterial
      and fungal pathogens must overcome the nutritional immunity of the host to be
      virulent. This review highlights the recent work toward exploiting the
      biosynthetic enzymes of siderophore production for the design of next generation
      antimicrobials. 

PMID- 25970812
TI  - Higher nocturnal and awake oxygen saturations in children with sickle cell
      disease receiving hydroxyurea therapy.
AB  - RATIONALE: Obstructive sleep apnea and intermittent nocturnal oxygen
      desaturations are highly prevalent in children with sickle cell disease and have
      been reported to contribute to associated morbidity, including vasoocclusive
      disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell
      disease and has been shown to decrease the number and severity of vasoocclusive
      crises. Although there has been an increase in the use of HU, the impact of HU on
      the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well
      documented. OBJECTIVES: To evaluate whether the use of HU is associated with a
      decreased frequency of obstructive sleep apnea and higher nocturnal and awake
      oxygen saturations (SaO2) in children with sickle cell disease. METHODS: This was
      a retrospective, cross-sectional review of children with sickle cell disease
      referred to the sleep laboratory at the Hospital for Sick Children, Toronto,
      Canada. Polysomnogram data in children with sickle cell disease receiving HU
      therapy were compared with those not prescribed HU. MEASUREMENTS AND MAIN
      RESULTS: Children with sickle cell disease receiving HU therapy (HU group, n =
      37) were matched with children not receiving HU (no-HU group, n = 104).
      Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in
      the HU group and no-HU groups, respectively (P = 0.14). The median obstructive
      apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU
      group, respectively (P = 0.28). The HU group compared with the no-HU group had a
      significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P <
      0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively;
      P < 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%,
      respectively; P = 0.0002). CONCLUSIONS: In children with sickle cell disease, the
      use of HU was associated with an increase in awake and nocturnal SaO2, despite
      there being no difference in the frequency of obstructive sleep apnea and the
      severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be
      an important mechanism of action of HU therapy. The use of HU to improve
      nocturnal saturations across the severity spectrum of sickle cell disease may be
      beneficial in decreasing morbidities related to sickle cell disease.

PMID- 25970813
TI  - Ruthenium-Catalyzed Olefin Cross-Metathesis with Tetrafluoroethylene and
      Analogous Fluoroolefins.
AB  - This Communication describes a successful olefin cross-metathesis with
      tetrafluoroethylene and its analogues. A key to the efficient catalytic cycle is
      interconversion between two thermodynamically stable, generally considered
      sluggish, Fischer carbenes. This newly demonstrated catalytic transformation
      enables easy and short-step synthesis of a new class of partially fluorinated
      olefins bearing plural fluorine atoms, which are particularly important and
      valuable compounds in organic synthesis and medicinal chemistry as well as the
      materials and polymer industries. 

PMID- 25970814
TI  - Cardiovascular risks associated with second-line oral antidiabetic agents added
      to metformin in patients with Type 2 diabetes: a nationwide cohort study.
AB  - AIM: To compare the cardiovascular risks associated with second-line oral
      antidiabetic agents added to initial metformin therapy in a large nationwide
      observational study. METHODS: We conducted a nationwide retrospective cohort
      study using the Taiwan National Health Insurance database. A total of 36 118
      users of different add-on oral antidiabetic agents (sulphonylureas, glinides,
      pioglitazone, alpha-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors)
      after initial metformin therapy were included in the analysis. The reference
      group was sulphonylureas added to metformin, the most commonly used combination
      regimen. The main outcomes of interest were hospitalizations for any
      cardiovascular event including acute myocardial infarction, congestive heart
      failure and ischaemic stroke. In the main analysis, all patients were followed
      within their initiation groups until the study end, disregarding any changes in
      treatment status over time. RESULTS: In intention-to-treat analyses, there was no
      difference in the risk of any cardiovascular event among the add-on combination
      treatment groups, but significantly lower risks of acute myocardial infarction
      were found for the glinides plus metformin treatment group (crude hazard ratio
      0.52, adjusted hazard ratio 0.39; 95% CI 0.20-0.75) and for the alpha-glucosidase
      inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted
      hazard ratio 0.54; 95% CI 0.31-0.95). No difference in risk of congestive heart
      failure or ischaemic stroke risk was found among the combination treatment
      groups. In secondary as-treated analyses, similar but less significant
      associations were found as compared with the primary intention-to-treat analyses
      for all treatment groups. CONCLUSION: There were no differences in overall
      cardiovascular risks among several add-on second-line oral antidiabetic agents;
      however, glinide plus metformin and alpha-glucosidase inhibitors plus metformin
      combination therapies might be associated with lower risks of acute myocardial
      infarction.

PMID- 25970811
TI  - Marginally hydrophobic transmembrane alpha-helices shaping membrane protein
      folding.
AB  - Cells have developed an incredible machinery to facilitate the insertion of
      membrane proteins into the membrane. While we have a fairly good understanding of
      the mechanism and determinants of membrane integration, more data is needed to
      understand the insertion of membrane proteins with more complex insertion and
      folding pathways. This review will focus on marginally hydrophobic transmembrane
      helices and their influence on membrane protein folding. These weakly hydrophobic
      transmembrane segments are by themselves not recognized by the translocon and
      therefore rely on local sequence context for membrane integration. How can such
      segments reside within the membrane? We will discuss this in the light of
      features found in the protein itself as well as the environment it resides in.
      Several characteristics in proteins have been described to influence the
      insertion of marginally hydrophobic helices. Additionally, the influence of
      biological membranes is significant. To begin with, the actual cost for having
      polar groups within the membrane may not be as high as expected; the presence of
      proteins in the membrane as well as characteristics of some amino acids may
      enable a transmembrane helix to harbor a charged residue. The lipid environment
      has also been shown to directly influence the topology as well as membrane
      boundaries of transmembrane helices-implying a dynamic relationship between
      membrane proteins and their environment. 

PMID- 25970815
TI  - Spontaneous resolution, asymmetric catalysis, and fluorescence properties of
      delta- and lambda-[cu(tzmp)]N enantiomers from in situ [2 + 3] cycloaddition
      synthesis.
AB  - Although a number of acentric or chiral tetrazole complexes were synthesized from
      Sharpless reaction, there are no spontaneous resolution Cu(I)-tetrazole compounds
      from in situ [2 + 3] cycloaddition synthesis that have been reported before. The
      first enantiomers Delta- and Lambda- of metal tetrazole compound [Cu(Tzmp)]n (1)
      (HTzmp = 3-tetrazolemethylpyridine) were obtained and isolated from in situ [2 +
      3] cycloaddition reactions of a flexible organic nitrile (3-cyanomethylpyridine)
      with sodium azide in the presence of CuCl2 as the Lewis acid. Delta-1 and Lambda
      1 feature a homochiral helical coordination polymeric system and {4(4).6(2)} two
      dimensional framework. The photoluminescence study suggests 1 exhibits strong
      green fluorescence in solid state with maximal emission peaks around 535 nm.
      Remarkably, the Delta- and Lambda- of [Cu(Tzmp)]n (1) catalyzes the
      enantioselective Henry reaction with high yield (more than 96%) and certain
      enantioselectivity (up to 69%). 

PMID- 25970816
TI  - Protective effects of berberine against doxorubicin-induced cardiotoxicity in
      rats by inhibiting metabolism of doxorubicin.
AB  - 1. The clinical use of doxorubicin, an effective anticancer drug, is severely
      hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been
      reported to possess cardioprotective and antitumor effects. In this study, we
      investigated the cardioprotective effect of berberine on doxorubicin-induced
      cardiotoxicity and the effect of berberine on the metabolism of doxorubicin. 2.
      Adult male Sprague-Dawley rats were administered doxorubicin in the presence or
      absence of berberine for 2 weeks. Administration of berberine effectively
      prevented doxorubicin-induced body weight reduction and mortality in rats. 3.
      Berberine reduced the activity of myocardial enzymes, including aspartate
      aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate
      dehydrogenase (LDH). Echocardiographic examination further demonstrated that
      berberine effectively ameliorated cardiac dysfunction induced by doxorubicin. 4.
      Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart
      and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of
      doxorubicin) in heart. 5. These data showed that berberine alleviated the
      doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of
      doxorubicin and reduced accumulation of doxorubicinol selectively in hearts. 

PMID- 25970817
TI  - Comment on: Nephron-sparing surgery (NSS) for unilateral Wilms tumor (uWT): The
      SIOP 2001 experience.

PMID- 25970818
TI  - Anion complexation with cyanobenzoyl substituted first and second generation
      tripodal amide receptors: crystal structure and solution studies.
AB  - Anion complexation properties of two new tripodal amide receptors have been
      extensively studied here. Two tripodal receptors have been synthesized from the
      reaction of cyanobenzoyl acid chloride with two tri-amine building blocks such as
      (i) tris(2-aminoethyl)amine and (ii) tris(2-(4-aminophenoxy)ethyl)amine, which
      resulted in the first (L1) and second (L2) generation tripodal amides
      respectively. A detailed comparison of their coordination behavior with anions is
      also described by crystallographic and solution state experiments. The crystal
      structure demonstrates various types of spatial orientations of tripodal arms in
      two receptors and concomitantly interacts with anions distinctively.
      Intramolecular H-bonding between amide N-H and CO prevents opening of the
      receptor cavity in the crystal, which leads to a locked conformation of L1 having
      C(3v) symmetry and makes amide hydrogen unavailable for the anion which results
      in side cleft anion binding. However, in L2 we conveniently shift the anion
      binding sites to a distant position which increases cavity size as well as rules
      out any intramolecular H-bonding between amide N-H and CO. The crystal structure
      shows a different orientation of the arms in L2; it adopts a quasi-planar
      arrangement with C(2v) symmetry. In the crystal structure two arms are pointed in
      the same direction and while extending the contact the third arm is H-bonded with
      the apical N-atom through a -CN group, making a pseudo capsular cavity where the
      anion interacts. Most importantly spatial reorientation of the receptor L2 from a
      C(2v) symmetry to a folded conformation with a C(3v) symmetry was observed only
      in the presence of an octahedral SiF6(2-) anion and forms a sandwich type
      complex. Receptors L1 and L2 are explored for their solution state anion binding
      abilities. The substantial changes in chemical shifts were observed for the amide
      (-NH) and aromatic hydrogen (-CH) (especially for F(-)), indicating the role of
      these hydrogens in anion binding. The anion interacts with receptor L2 more
      strongly than L1 as confirmed by 1H NMR titration upon monitoring the -NH signal.

PMID- 25970819
TI  - The Preservation and Handling of Vein Grafts in Current Surgical Practice:
      Findings of a Survey Among Cardiovascular Surgeons of Top-Ranked US Hospitals.

PMID- 25970820
TI  - Early rhizosphere microbiome composition is related to the growth and Zn uptake
      of willows introduced to a former landfill.
AB  - Although plants introduced for site restoration are pre-selected for specific
      traits (e.g. trace element bioaccumulation, rapid growth in poor soils), the in
      situ success of these plants likely depends on the recruitment of appropriate
      rhizosphere microorganisms from their new environment. We introduced three willow
      (Salix spp.) cultivars to a contaminated landfill, and performed soil chemical
      analyses, plant measurements, and Ion Torrent sequencing of rhizospheric fungal
      and bacterial communities at 4 and 16 months post-planting. The abundance of
      certain dominant fungi was linked to willow accumulation of Zn, the most abundant
      trace element at the site. Interestingly, total Zn accumulation was better
      explained by fungal community structure 4 months post-planting than 16 months
      post-planting, suggesting that initial microbial recruitment may be critical. In
      addition, when the putative ectomycorrhizal fungi Sphaerosporella brunnea and
      Inocybe sp. dominated the rhizosphere 4 months post-planting, Zn accumulation
      efficiency was negatively correlated with fungal diversity. Although field
      studies such as this rely on correlation, these results suggest that the soil
      microbiome may have the greatest impact on plant function during the early stages
      of growth, and that plant-fungus specificity may be essential. 

PMID- 25970821
TI  - The doping effect on the catalytic activity of graphene for oxygen evolution
      reaction in a lithium-air battery: a first-principles study.
AB  - A lithium-air battery as an energy storage technology can be used in electric
      vehicles due to its large energy density. However, its poor rate capability, low
      power density and large overpotential problems limit its practical usage. In this
      paper, the first-principles thermodynamic calculations were performed to study
      the catalytic activity of X-doped graphene (X = B, N, Al, Si, and P) materials as
      potential cathodes to enhance charge reactions in a lithium-air battery. Among
      these materials, P-doped graphene exhibits the highest catalytic activity in
      reducing the charge voltage by 0.25 V, while B-doped graphene has the highest
      catalytic activity in decreasing the oxygen evolution barrier by 0.12 eV. By
      combining these two catalytic effects, B,P-codoped graphene was demonstrated to
      have an enhanced catalytic activity in reducing the O2 evolution barrier by 0.70
      eV and the charge voltage by 0.13 V. B-doped graphene interacts with Li2O2 by Li
      sited adsorption in which the electron-withdrawing center can enhance charge
      transfer from Li2O2 to the substrate, facilitating reduction of O2 evolution
      barrier. In contrast, X-doped graphene (X = N, Al, Si, and P) prefers O-sited
      adsorption toward Li2O2, forming a X-O2(2-)...Li(+) interface structure between X
      O2(2-) and the rich Li(+) layer. The active structure of X-O2(2-) can weaken the
      surrounding Li-O2 bonds and significantly reduce Li(+) desorption energy at the
      interface. Our investigation is helpful in developing a novel catalyst to enhance
      oxygen evolution reaction (OER) in Li-air batteries.

PMID- 25970822
TI  - Multielement stoichiometry of submerged macrophytes across Yunnan plateau lakes
      (China).
AB  - Stoichiometric homeostasis of element composition is one of the central concepts
      of ecological stoichiometry. We analyzed concentrations of macroelements (C, N,
      P, Ca, K, Mg, S), microelements (Cu, Fe, Mn, Mo, Ni, Zn) and beneficial elements
      (Na, Se, Si) in submerged macrophytes, water and sediments across 20 Yunnan
      plateau lakes. We predicted that tissue element composition in submerged
      macrophytes is affected by lake trophic level and taxonomy, and submerged
      macrophytes have weak stoichiometric homeostasis for all above 16 elements.
      Canonical discriminant analyses successfully discriminated among trophic level
      groups and taxa groups. Of all the elements, C, N, P and S most effectively
      discriminated among trophic level groups across 20 lakes, revealing lake trophic
      level mostly affect tissue macroelement composition in submerged macrophytes;
      while Ca, K and Se most effectively discriminated among submerged macrophytes
      taxa groups, suggesting taxonomy mostly affect compositions of macroelements and
      beneficial elements in submerged macrophytes. In addition, the stoichiometric
      homeostatic coefficient of 1/HCa:C for all five taxa of submerged macrophytes
      were less than zero, suggesting submerged macrophytes in Yunnan plateau lakes
      have strong Ca stoichiometric homeostasis. Our findings, not only broaden the
      knowledge of multielement stoichiometric homeostasis, but also help to choose
      most appropriate lake management strategy. 

PMID- 25970823
TI  - Generation and characterization of large-particle aerosols using a center flow
      tangential aerosol generator with a non-human-primate, head-only aerosol chamber.
AB  - Aerosol droplets or particles produced from infected respiratory secretions have
      the potential to infect another host through inhalation. These respiratory
      particles can be polydisperse and range from 0.05 to 500 um in diameter. Animal
      models of infection are generally established to facilitate the potential
      licensure of candidate prophylactics and/or therapeutics. Consequently, aerosol
      based animal infection models are needed to properly study and counter airborne
      infections. Ideally, experimental aerosol exposure should reliably result in
      animal disease that faithfully reproduces the modeled human disease. Few studies
      have been performed to explore the relationship between exposure particle size
      and induced disease course for infectious aerosol particles. The center flow
      tangential aerosol generator (CenTAGTM) produces large-particle aerosols capable
      of safely delivering a variety of infectious aerosols to non-human primates
      (NHPs) within a Class III Biological Safety Cabinet (BSC) for establishment or
      refinement of NHP infectious disease models. Here, we report the adaptation of
      this technology to the Animal Biosafety Level 4 (ABSL-4) environment for the
      future study of high-consequence viral pathogens and the characterization of
      CenTAGTM-created sham (no animal, no virus) aerosols using a variety of viral
      growth media and media supplements. 

PMID- 25970824
TI  - Bone marrow-derived mesenchymal stem cells attenuate phosgene-induced acute lung
      injury in rats.
AB  - Accidental phosgene exposure could result in acute lung injury (ALI), effective
      therapy is needed for the patients with phosgene-induced ALI. As a type of cells
      with therapeutic potential, mesenchymal stem cells (MSCs) have been showed its
      efficacy in multiple diseases. Here, we assessed the therapeutic potential of
      MSCs in phosgene-induced ALI and explored the related mechanisms. After isolation
      and characterization of rat bone marrow MSCs (BMMSCs), we transplanted BMMSCs
      into the rats exposed to phosgene and observed significant improvement on the
      lung wet-to-dry ratio and partial oxygen pressure (PaO2) at 6, 24, 48 h after
      phosgene exposure. Histological analyses revealed reduced sign of pathological
      changes in the lungs. Reduced level of pro-inflammatory tumor necrosis factor
      alpha and increased level of anti-inflammatory factor interleukin-10 were found
      in both bronchoalveolar lavage and plasma. Significant increased expression of
      epithelial cell marker AQP5 and SP-C was also found in the lung tissue. In
      conclusion, treatment with MSC markedly decreases the severity of phosgene
      induced ALI in rats, and these protection effects were closely related to the
      pulmonary air blood barrier repairment and inflammatory reaction regulation. 

PMID- 25970826
TI  - Effects of pH on the silk fibroin coating of CoCrMo alloy.
AB  - Bacteria related infections are still cited as a major problem for the implant
      materials resulting in failure of device especially knee and hip replacement. Two
      main approaches are focused for inhibiting the bacterial adhesion to the surface.
      These involve bactericidal substances and anti-adhesive coatings. Silk fibroin is
      one of the promising materials due to its good drug loading capacity and
      efficiency. In this study, the effects of pH on the silk fibroin coating of
      CoCrMo alloy, prepared by means of layer by layer, was investigated thoroughly
      using scanning electron microscope (SEM), Atomic Force Microscope (AFM)
      Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) Spectroscopy.
      A medical grade CoCrMo was coated with variable number of silk fibroin up to 14
      layers at pH 3.0, 3.5, and 5.5 at room temperature. As a result, only silk
      fibroin films prepared at pH 3.0 and 3.5 were found to convey the general
      characteristics of the mixture of silk I and II, while the samples prepared at pH
      5.5 exhibited the lack of some specific amide structures which influence the
      general characteristics of silk I and II. Moreover, regardless of pH, the surface
      roughness was determined to increase with the increasing number of layers.
      However, as the pH increases the surface roughness decreases at 6, 10 and 14
      layers.

PMID- 25970825
TI  - Comparative analysis of the Dicer-like gene family reveals loss of miR162 target
      site in SmDCL1 from Salvia miltiorrhiza.
AB  - DCL1, the core component for miRNA biogenesis, is itself regulated by miR162 in
      Arabidopsis. MiRNA-mediated feedback regulation of AtDCL1 is important to
      maintain the proper level of DCL1 transcripts. However, it is unknown whether the
      miRNA-mediated regulation of DCL1 is conserved among plants. We analyzed the
      SmDCL gene family in Salvia miltiorrhiza, an emerging model plant for Traditional
      Chinese Medicine (TCM) studies, using a comprehensive approach integrating genome
      wide prediction, molecular cloning, gene expression profiling, and
      posttranscriptional regulation analysis. A total of five SmDCLs were identified.
      Comparative analysis of SmDCLs and AtDCLs showed an apparent enlargement of SmDCL
      introns in S. miltiorrhiza. The absence of miR162 in S. miltiorrhiza and the loss
      of miR162 target site in SmDCL1 were unexpectedly found. Further analysis showed
      that the miR162 target site was not present in DCL1 from ancient plants and was
      gained during plant evolution. The gained miR162 target site might be lost in a
      few modern plants through nucleotide mutations. Our results provide evidence for
      the gain and loss of miR162 and its target sites in Dicer-like genes during
      evolution. The data is useful for understanding the evolution of miRNA-mediated
      feedback regulation of DCLs in plants. 

PMID- 25970827
TI  - Mutation analysis in Norwegian families with hereditary hemorrhagic
      telangiectasia: founder mutations in ACVRL1.
AB  - Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is an
      autosomal dominant inherited disease defined by the presence of epistaxis and
      mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in internal
      organs. In most families (~85%), HHT is caused by mutations in the ENG (HHT1) or
      the ACVRL1 (HHT2) genes. Here, we report the results of genetic testing of 113
      Norwegian families with suspected or definite HHT. Variants in ENG and ACVRL1
      were found in 105 families (42 ENG, 63 ACVRL1), including six novel variants of
      uncertain pathogenic significance. Mutation types were similar to previous
      reports with more missense variants in ACVRL1 and more nonsense, frameshift and
      splice-site mutations in ENG. Thirty-two variants were novel in this study. The
      preponderance of ACVRL1 mutations was due to founder mutations, specifically,
      c.830C>A (p.Thr277Lys), which was found in 24 families from the same geographical
      area of Norway. We discuss the importance of founder mutations and present a
      thorough evaluation of missense and splice-site variants.

PMID- 25970828
TI  - Otic placode cell specification and proliferation are regulated by Notch
      signaling in avian development.
AB  - BACKGROUND: The entire inner ear including the cochlear-vestibular ganglion
      arises from a simple epithelium, the otic placode. Precursors for the placode
      originate from a pool of progenitors located in ectoderm next to the future
      hindbrain, the pre-otic field, where they are intermingled with future
      epibranchial and epidermal cells. While the importance of secreted proteins, such
      as FGFs and Wnts, in imparting otic identity has been well studied, how
      precursors for these different fates segregate locally is less well understood.
      RESULTS: (1) The Notch ligand Delta1 and the Notch target Hes5-2 are expressed in
      a part of pre-otic field before otic commitment, indicative of active Notch
      signaling, and this is confirmed using a Notch reporter. (2) Loss and gain-of
      function approaches reveal that Notch signaling regulates both proliferation and
      specification of pre-otic progenitors. CONCLUSIONS: Our results identify a novel
      function of Notch signaling in cell fate determination in the pre-otic field of
      avian embryos.

PMID- 25970829
TI  - Exploiting SNPs for biallelic CRISPR mutations in the outcrossing woody perennial
      Populus reveals 4-coumarate:CoA ligase specificity and redundancy.

PMID- 25970830
TI  - Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase
      chain reaction after allogeneic hematopoietic stem cell transplantation: two case
      reports and review of the literature.
AB  - Toxoplasmic encephalitis represents a rare, but often fatal infection after
      allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction
      (PCR)-based preemptive therapy is considered promising for this disease, but is
      not routinely applied, especially in low seroprevalence countries including
      Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation
      that were successfully treated. The diagnosis of toxoplasmic encephalitis in
      these cases was confirmed by PCR testing when neurological symptoms were
      observed. Both patients received pyrimethamine and sulfadiazine treatments within
      2 weeks of the development of neurological symptoms, and remained free of
      recurrence for 32 and 12 months. These results emphasized the importance of the
      PCR test and immediate treatment after diagnosis for the management of
      toxoplasmic encephalitis.

PMID- 25970831
TI  - Nuclear Akt: target for breast cancer therapy?

PMID- 25970832
TI  - Scatter hoarding of seeds confers survival advantages and disadvantages to large
      seeded tropical plants at different life stages.
AB  - Scatter hoarding of seeds by animals contributes significantly to forest-level
      processes, including plant recruitment and forest community composition. However,
      the potential positive and negative effects of caching on seed survival,
      germination success, and seedling survival have rarely been assessed through
      experimental studies. Here, I tested the hypothesis that seed burial mimicking
      caches made by scatter hoarding Central American agoutis (Dasyprocta punctate)
      enhances seed survival, germination, and growth by protecting seeds from seed
      predators and providing favorable microhabitats for germination. In a series of
      experiments, I used simulated agouti seed caches to assess how hoarding affects
      seed predation by ground-dwelling invertebrates and vertebrates for four plant
      species. I tracked germination and seedling growth of intact and beetle-infested
      seeds and, using exclosures, monitored the effects of mammals on seedling
      survival through time. All experiments were conducted over three years in a
      lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped
      predation by both invertebrates and vertebrates while exposed seeds suffered high
      levels of infestation and removal. Hoarding had no effect on infestation rates of
      D. panamensis, but burial negatively affected germination success by preventing
      endocarp dehiscence. Non-infested palm seeds had higher germination success and
      produced larger seedlings than infested seeds. Seedlings of A. alatum and I.
      deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most
      seeds from predators and enhanced germination success (except for D. panamensis)
      and seedling growth, although mammals killed many seedlings of two plant species;
      all seedling deaths were due to seed removal from the plant base. Using
      experimental caches, this study shows that scatter hoarding is beneficial to most
      seeds and may positively affect plant propagation in tropical forests, although
      tradeoffs in seed survival do exist. 

PMID- 25970833
TI  - Vascular disease of the spine.
AB  - Vascular insults to the spinal cord are substantially less common than their
      corresponding events in the brain; it has been estimated, for example, that
      spinal cord infarcts make up <= 1% of ischemic events in the central nervous
      system. Although the public health burden of spinal cord injury remains severe,
      the majority of this burden stems from traumatic rather than vascular events.
      Still, vascular injuries in the spine are common enough and their consequences
      devastating enough that a familiarity with the pathophysiology, diagnosis, and
      treatment of the more common etiologies is essential to any practitioner of the
      clinical neurosciences. In this educational review, we will briefly outline the
      normal development and anatomy of the spinal vasculature, then focus on specific
      mechanisms of vascular injury to the spine. In particular, we will examine
      spontaneous and iatrogenic ischemic insults and their associated clinical
      syndromes, and then review vascular neoplasms and malformations of the spine with
      attention to the various management strategies that currently exist for these
      complex lesions. Finally, we will briefly address the future areas for
      exploration, including investigative avenues for neuroprotection, as well as the
      possible influence of atherosclerotic disease on spinal degenerative disease and
      low back pain.

PMID- 25970834
TI  - Differential diagnosis of finger drop.
AB  - Finger drop is a useful clinical sign which is easy to elicit. This article
      presents a logical approach for assessing patients with finger drop and outlines
      the important causes, and how to differentiate them. Patients with finger drop
      may present either to orthopedic surgeons or to neurologists, and both
      specialists should be aware of important diagnoses in their complementary fields.

PMID- 25970835
TI  - Paroxysmal dystonia as a manifestation of multiple sclerosis.
AB  - INTRODUCTION: Paroxysmal dystonia is a rare manifestation of multiple sclerosis
      (MS). CASE REPORT: A 41-year-old man presented to our Emergency Department with
      sudden and repeated episodes of left upper limb flexion and lower limb extension.
      His medical history included an episode of left facial palsy a year earlier.
      Neurological examination demonstrated only brisk deep tendon reflexes on the left
      upper limb. Routine blood and urine analyses were normal. Computed tomography of
      the brain and cervical Doppler were normal. Aspirin and sodium valproate were
      started, without improvement. Video-EEG monitoring revealed no electrographic
      abnormality synchronous with these paroxysmal events, excluding epileptic nature.
      Cerebral magnetic resonance imaging showed multiple T2 white matter lesions at
      the midbrain, right diencephalon, corpus callosum, cervical, and thoracic spinal
      cord. The right diencephalic lesion enhanced with gadolinium. Complete basic and
      immunologic analysis and serological studies were normal or negative. Oligoclonal
      bands were positive in cerebrospinal fluid (negative in serum).
      Methylprednisolone (1 g/d for 5 d) was started without clinical improvement.
      Carbamazepine (400 mg/d) was promptly effective, and discontinued after 1 month
      without recurrence. DISCUSSION: The patient met the criteria for the diagnosis of
      MS according to the 2010 McDonald criteria. The timely and accurate diagnosis of
      MS requires the recognition of its varied and atypical clinical manifestations.

PMID- 25970836
TI  - Acute global ischemic stroke after cranioplasty: case report and review of the
      literature.
AB  - INTRODUCTION: Cranioplasty procedures are performed usually after devastating
      neurological injuries requiring craniectomies. Although relatively safe, global
      intracerebral infarction is a poorly understood, and most often, lethal
      complication after cranioplasty. We report here one such case with a thorough
      literature review with insight as to possible etiologies of this injury. CASE
      REPORT: A 14-year-old girl underwent a left-sided decompressive hemicraniectomy
      for treatment of a subdural hematoma and cerebral edema. The patient's
      neurological condition eventually improved and she presented for cranioplasty
      repair of the defect 83 days after her initial operation. Six hours after an
      uneventful procedure, the patient's neurological examination declined. Immediate
      CT scan revealed global edema. Despite all treatment measures, the patient
      progressed to global ischemia and brain death and expired. CONCLUSIONS: Although
      global intracerebral infarction after cranioplasty is extremely rare, the
      concepts of vessel injury, venous stasis, and reperfusion into dysfunctional
      cerebral tissue after cranioplasty should be considered when evaluating the risk
      of this procedure.

PMID- 25970837
TI  - Superior sagittal sinus thrombus secondary to occult meningioma: a case report.
AB  - A 58-year-old man presented with intermittent white flashes in both eyes during
      the past year. Six years earlier (2004), the patients received a diagnosis of
      superior sagittal sinus (SSS) thrombosis on the basis of elevated intracranial
      pressure and imaging findings, for example, computed tomography, magnetic
      resonance imaging, magnetic resonance venography, and cerebral angiography, and
      was treated with urokinase and anticoagulatants. Symptoms resolved and the
      patient remained well until March 2009, when intermittent white flashes started
      to occur in both the eyes. The patient did not seek medical help until 1 year
      later (March 2010). Cerebral angiography (digital subtraction arteriography)
      revealed SSS thrombosis and a network of collateral venous circulation. Computed
      tomography and magnetic resonance imaging demonstrated a mass in the
      parietooccipital lobe that surrounded the SSS. Pathologic examination of the
      specimen removed during surgery revealed meningioma. 

PMID- 25970838
TI  - IVIG Versus PLEX in the Treatment of Worsening Myasthenia Gravis: What is the
      Evidence?: A Critically Appraised Topic.
AB  - BACKGROUND: Immune therapies such as intravenous immunoglobulin (IVIG) and plasma
      exchange (PLEX) are first line in the treatment of worsening myasthenia gravis.
      Although PLEX is favored in myasthenic crisis, IVIG is increasingly used in
      exacerbations due to cost and ease of administration. OBJECTIVES: To review and
      critically assess current evidence on the effects of IVIG and PLEX on functional
      outcomes in patients with worsening myasthenia gravis. METHODS: A structured
      critical appraisal was conducted on the objective topic. This included a creation
      of a structured question based on a clinical scenario, comprehensive literature
      search, selection of evidence for review, and critical appraisal of selected
      evidence. Evidence was summarized and commentary provided. Participants included
      consultant and resident neurologists, a medical librarian, clinical
      epidemiologists, and content experts in the field of neuromuscular neurology.
      RESULTS: A single-blinded, randomized-controlled trial that compared IVIG and
      PLEX in 84 patients with worsening myasthenia gravis was selected for review.
      Primary outcome measure was functional status at 14 days after treatment, as
      assessed by the Quantitative Myasthenia Gravis Score. Change in Quantitative
      Myasthenia Gravis Score at day 14 for all subjects was 4.0, without statistically
      significant differences between IVIG and PLEX groups. CONCLUSIONS: IVIG and PLEX
      are equally effective in worsening myasthenia gravis. Treatment decisions may
      depend on several variables, including presence of respiratory distress, medical
      comorbidities, access to medication, and cost. PLEX will likely remain the
      treatment of choice in true myasthenic crisis.

PMID- 25970839
TI  - Provotella-derived hydrogen sulfide, constipation, and neuroprotection in
      Parkinson's disease.

PMID- 25970840
TI  - Protein Kinase C Isoforms Distinctly Regulate Propofol-induced Endothelium
      dependent and Endothelium-independent Vasodilation.
AB  - Protein kinase C (PKC) isoforms improve endothelial nitric oxide synthase
      activity and contractile Ca sensitivity in blood vessels. These actions may have
      opposite effects on propofol-induced vasodilation. This study examines the
      hypothesis that propofol induces relaxation by enhancing the PKC-mediated nitric
      oxide synthesis in endothelium and/or inhibiting the PKC-regulated Ca sensitivity
      in vascular smooth muscle (VSM). Propofol (1-100 MUM) induced greater relaxation
      in endothelium-intact rings compared with denuded rings, and this effect was
      antagonized by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME). In contrast, treatment with the general PKC inhibitor GF-109203X
      augmented both the endothelium-dependent and endothelium-independent relaxation
      induced by propofol, and this enhancement was more profound in the intact rings
      at lower propofol concentrations. The enhancement was unaffected by L-NAME.
      Interestingly, calphostin C (an inhibitor of conventional and novel PKCs) and Go
      6976 (an inhibitor of conventional PKCs) had similar effects in augmenting
      propofol-induced relaxation in endothelium-denuded rings. Downregulation of novel
      isoforms not only reduced the norepinephrine-elicited contraction but also
      decreased the magnitude of propofol-induced relaxation. In vascular smooth muscle
      cells, propofol prevented norepinephrine-elicited phosphorylation of myosin light
      chain. Propofol can increase the PKC-mediated availability of nitric oxide but
      inhibit the novel PKC-regulated Ca-sensitization, which provides a novel
      explanation for the mechanism of propofol-induced vasodilation. 

PMID- 25970842
TI  - Autonomic Remodeling: How Atrial Fibrillation Begets Atrial Fibrillation in the
      First 24 Hours.
AB  - BACKGROUND: The mechanism(s) of how atrial fibrillation (AF) sustains itself in
      the first 24 hours is not well understood. OBJECTIVE: We sought to investigate
      the role of autonomic remodeling in the first 24 hours of AF simulated by rapid
      atrial pacing (RAP). METHODS: Forty-eight rabbits were divided into 6 groups. One
      group (n = 8) was euthanized after baseline recordings. Another group (n = 8) did
      not receive RAP during the 24-hour period to serve as controls. In the other 4
      groups, rabbits were euthanized after RAP for 4, 8, 12, or 24 hours (n = 8 for
      each). Before and after designated hours of RAP, atrial effective refractory
      period, heart rate variability, and left vagal and sympathetic nerve activity
      (VNA and SNA, respectively) were determined. The right and left atrial tissues
      were obtained for immunocytochemical analysis for growth-associated protein 43
      (GAP43), tyrosine hydroxylase (TH), and choline acetyltransferase (ChAT).
      RESULTS: RAP resulted in progressively shortened atrial effective refractory
      period and slower heart rate. In the first 12 hours of RAP, both SNA and VNA
      progressively increased. Then, VNA remained stably elevated but SNA began to
      attenuate. The high-frequency component and low-frequency/high-frequency ratio of
      heart rate variability followed the trend of VNA and SNA, respectively. The
      density of GAP43-positive, ChAT-positive, and TH-positive neural elements in the
      right and left atria was progressively higher with RAP. CONCLUSIONS: AF resulted
      in progressive autonomic remodeling, manifesting as nerve sprouting, sympathetic
      and vagal hyperinnervation. Autonomic remodeling may play an important role in
      sustaining AF in the first 24 hours.

PMID- 25970843
TI  - CytoSource: Current Issues for Cytopathology.

PMID- 25970841
TI  - The Role of Pharmacogenetics in Atrial Fibrillation Therapeutics: Is Personalized
      Therapy in Sight?
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia
      worldwide requiring therapy. Despite recent advances in catheter-based and
      surgical therapy, antiarrhythmic drugs (AADs) remain the mainstay of treatment
      for symptomatic AF. However, response in individual patients is highly variable
      with over half the patients treated with rhythm control therapy experiencing
      recurrence of AF within a year. Contemporary AADs used to suppress AF are
      incompletely and unpredictably effective and associated with significant risks of
      proarrhythmia and noncardiac toxicities. Furthermore, this "one-size" fits all
      strategy for selecting antiarrhythmics is based largely on minimizing risk of
      adverse effects rather than on the likelihood of suppressing AF. The limited
      success of rhythm control therapy is in part due to heterogeneity of the
      underlying substrate, interindividual differences in disease mechanisms, and our
      inability to predict response to AADs in individual patients. Genetic studies of
      AF over the past decade have revealed that susceptibility to and response to
      therapy for AF is modulated by the underlying genetic substrate. However, the
      bedside application of these new discoveries to the management of AF patients has
      thus far been disappointing. This may in part be related to our limited
      understanding about genetic predictors of drug response in general, the
      challenges associated with determining efficacy of response to AADs, and lack of
      randomized genotype-directed clinical trials. Nonetheless, recent studies have
      shown that common AF susceptibility risk alleles at the chromosome 4q25 locus
      modulated response to AADs, electrical cardioversion, and ablation therapy. This
      monograph discusses how genetic approaches to AF have not only provided important
      insights into underlying mechanisms but also identified AF subtypes that can be
      better targeted with more mechanism-based "personalized" therapy. 

PMID- 25970844
TI  - Technology and Technique Standards for Camera-Acquired Digital Dermatologic
      Images: A Systematic Review.
AB  - IMPORTANCE: Photographs are invaluable dermatologic diagnostic, management,
      research, teaching, and documentation tools. Digital Imaging and Communications
      in Medicine (DICOM) standards exist for many types of digital medical images, but
      there are no DICOM standards for camera-acquired dermatologic images to date.
      OBJECTIVE: To identify and describe existing or proposed technology and technique
      standards for camera-acquired dermatologic images in the scientific literature.
      EVIDENCE REVIEW: Systematic searches of the PubMed, EMBASE, and Cochrane
      databases were performed in January 2013 using photography and digital imaging,
      standardization, and medical specialty and medical illustration search terms and
      augmented by a gray literature search of 14 websites using Google. Two reviewers
      independently screened titles of 7371 unique publications, followed by 3
      sequential full-text reviews, leading to the selection of 49 publications with
      the most recent (1985-2013) or detailed description of technology or technique
      standards related to the acquisition or use of images of skin disease (or related
      conditions). FINDINGS: No universally accepted existing technology or technique
      standards for camera-based digital images in dermatology were identified.
      Recommendations are summarized for technology imaging standards, including
      spatial resolution, color resolution, reproduction (magnification) ratios,
      postacquisition image processing, color calibration, compression, output,
      archiving and storage, and security during storage and transmission.
      Recommendations are also summarized for technique imaging standards, including
      environmental conditions (lighting, background, and camera position), patient
      pose and standard view sets, and patient consent, privacy, and confidentiality.
      Proposed standards for specific-use cases in total body photography,
      teledermatology, and dermoscopy are described. CONCLUSIONS AND RELEVANCE: The
      literature is replete with descriptions of obtaining photographs of skin disease,
      but universal imaging standards have not been developed, validated, and adopted
      to date. Dermatologic imaging is evolving without defined standards for camera
      acquired images, leading to variable image quality and limited exchangeability.
      The development and adoption of universal technology and technique standards may
      first emerge in scenarios when image use is most associated with a defined
      clinical benefit.

PMID- 25970845
TI  - Long-term frequent use of non-steroidal anti-inflammatory drugs might protect
      patients with ankylosing spondylitis from cardiovascular diseases: a nationwide
      case-control study.
AB  - The objective of this case-control study was to investigate the risk of
      cardiovascular disease (CVD) following non-steroidal anti-inflammatory drug
      (NSAID) use in patients with ankylosing spondylitis (AS). A total of 10,763 new
      AS patients were identified from the National Taiwan Health Insurance claims
      database during the period from 1997 to 2008. In all, 421 AS patients with CVD
      were recruited as cases, and up to 2-fold as many sex- and age-matched controls
      were selected. Logistic regression models were used to estimate the odds ratio
      (OR) between NSAID use and CVD incidence. The medication possession rate (MPR)
      was used to evaluate NSAID exposure during the study period. AS patients had
      increased risk of CVD (OR, 1.68; 95% confidence interval (CI), 1.57 to 1.80).
      Among frequent (MPR>=80%) COX II users, the risks for all types of CVD were ten
      times lower than those among non-users at 24 months (OR, 0.08; 95% CI, 0.01 to
      0.92). Among frequent NSAID users, the risks of major adverse cardiac event
      (MACE) were significantly lower at 12 months (OR, 0.23; 95% CI, 0.07 to 0.76)--a
      trend showing that longer exposure correlated with lower risk. Regarding non
      frequent NSAID users (MPR<80%), short-term exposure did carry higher risk (for 6
      months: OR, 1.41; 95% CI, 1.07 to 1.86), but after 12 months, the risk no longer
      existed. We conclude that long-term frequent use of NSAIDs might protect AS
      patients from CVD; however, NSAIDs still carried higher short-term risk in the
      non-frequent users.

PMID- 25970847
TI  - Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of
      adverse perinatal outcome.
AB  - OBJECTIVE: To investigate the potential value of uterine artery (UtA) Doppler at
      30-34 weeks' gestation in the prediction of adverse perinatal outcome. METHODS:
      This was a screening study in 30 780 singleton pregnancies at 30-34 weeks. UtA
      pulsatility index (UtA-PI) was measured and the values were converted to
      multiples of the median (MoM) after adjustment for variables relating to maternal
      characteristics and medical history that affect the measurements. Multivariable
      logistic regression analysis was used to determine if measuring UtA-PI improved
      the prediction of adverse perinatal outcome provided by screening with maternal
      characteristics, medical history and obstetric factors. The detection rate (DR)
      and false-positive rate (FPR) of screening by UtA-PI were estimated for
      stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH
      <= 7.0 or umbilical venous cord blood pH <= 7.1 and 5-min Apgar score < 7.
      RESULTS: The incidence of adverse perinatal outcome was higher in small-for
      gestational-age (SGA) fetuses than in non-SGA fetuses, but the majority of cases
      with each adverse outcome were in the non-SGA group, including about 70% of
      stillbirths and more than 80% with Cesarean section for fetal distress, low cord
      blood pH and low Apgar score. The performance of UtA-PI > 95(th) percentile in
      screening for each adverse outcome was poor with DR of 6-16% and a FPR of 5-6%.
      The DR of adverse outcome when screening by high UtA-PI was greater in
      pregnancies complicated by SGA than in non-SGA pregnancies; 24% vs 13% for
      stillbirth, 15% vs 5% for Cesarean section for fetal distress, 30% vs 9% for low
      cord blood pH and 20% vs 3% for low 5-min Apgar score, respectively. CONCLUSION:
      High UtA-PI at 30-34 weeks' gestation may be useful in the prediction of adverse
      perinatal outcome in pregnancies with a SGA fetus, however, in the absence of
      SGA, UtA-PI is a poor predictor of adverse outcome. Copyright (c) 2015 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 25970848
TI  - Preparation of asparagine-linked monoglucosylated high-mannose-type
      oligosaccharide from egg yolk.
AB  - Monoglucosylated high-mannose-type glycan (Glc1Man9GlcNAc2: G1M9) is well-known
      as a key glycoform in the glycoprotein folding process, which is specifically
      recognized by lectin chaperones calnexin (CNX) and calreticulin (CRT) in the
      endoplasmic reticulum (ER). In this work, we developed an efficient method for
      the preparation of G1M9-Asn. The G1M9-Asn was obtained from the IgY-rich fraction
      derived from hen egg yolk by the digestion with pronase. The alpha-amino group of
      asparagine in G1M9-Asn was protected with the 9-fluorenylmethyloxycarbonyl (Fmoc)
      group and the labeled glycans were subsequently purified using high performance
      liquid chromatography (HPLC). This method will provide useful substrates for
      analysis of the glycoprotein folding cycle in the ER. 

PMID- 25970850
TI  - Hospital-Level Factors Associated With Mortality After Endovascular and Open
      Abdominal Aortic Aneurysm Repair.
AB  - IMPORTANCE: Endovascular technology has become ubiquitous in the modern care of
      abdominal aortic aneurysm (AAA), yet broad estimates of its efficacy among
      variable hospital and regional settings is not known. OBJECTIVE: To perform a
      preliminary analysis of hospital effects on mortality following open AAA repair
      (OAR) and endovascular AAA repair (EVAR). DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective analysis of the American College of Surgeons National Surgical
      Quality Improvement Program database was conducted on all patients undergoing OAR
      or EVAR from July 1, 2010, to November 30, 2012, using Current Procedural
      Terminology codes. MAIN OUTCOMES AND MEASURES: Weight-adjusted 30-day observed to
      expected mortality ratios were compared based on hospital type (academic vs
      community) and size (100-299 beds vs 300-500 beds vs >500 beds). RESULTS: Data on
      11,250 patients (2466 underwent OAR and 8784 underwent EVAR) were analyzed.
      Endovascular AAA repair was performed more frequently than OAR at both academic
      (78.8%) and community (68.2%) hospitals. Overall 30-day mortality was 14.0% for
      OAR and 4.3% for EVAR (P < .001). Hospital size was significantly associated with
      mortality for OAR (observed to expected mortality ratio: >500 beds, 0.88 vs 300
      500 beds, 1.11 vs 100-299 beds, 1.59; P = .01) but not for EVAR (P = .27). In
      contrast, hospital type was significantly associated with mortality for EVAR
      (observed to expected mortality ratio: academic, 0.60 vs community, 2.60; P <
      .001) but not OAR (P = .46). Multivariable analysis of hospital-level factors
      suggested that, for all outcomes, academic hospital type was the single most
      significant predictor of reduced mortality following AAA repair (observed to
      expected mortality ratio: academic, 0.91 vs community, 2.00; P = .05).
      CONCLUSIONS AND RELEVANCE: Based on this preliminary report, outcomes for both
      OAR and EVAR appear to depend greatly on hospital-level effects. The relative
      safety of EVAR vs OAR may depend on appropriate patient selection and adequate
      access to multidisciplinary care in order to minimize failure to rescue rates and
      improve survival.

PMID- 25970849
TI  - Collisional unfolding of multiprotein complexes reveals cooperative stabilization
      upon ligand binding.
AB  - Cooperative binding mechanisms are a common feature in biology, enabling a
      diverse range of protein-based molecular machines to regulate activities ranging
      from oxygen uptake to cellular membrane transport. Much, however, is not known
      about such cooperative binding mechanisms, including how such events typically
      add to the overall stability of such protein systems. Measurements of such
      cooperative stabilization events are challenging, as they require the separation
      and resolution of individual protein complex bound states within a mixture of
      potential stoichiometries to individually assess protein stabilities. Here, we
      report ion mobility-mass spectrometry results for the concanavalin A tetramer
      bound to a range of polysaccharide ligands. We use collision induced unfolding, a
      relatively new methodology that functions as a gas-phase analog of calorimetry
      experiments in solution, to individually assess the stabilities of concanavalin A
      bound states. By comparing the differences in activation voltage required to
      unfold different concanavalin A-ligand stoichiometries, we find evidence
      suggesting a cooperative stabilization of concanavalin A occurs upon binding most
      carbohydrate ligands. We critically evaluate this observation by assessing a
      broad range of ligands, evaluating the unfolding properties of multiple protein
      charge states, and by comparing our gas-phase results with those obtained from
      calorimetry experiments carried out in solution. 

PMID- 25970851
TI  - The importance of considering animal body mass in IPCC greenhouse inventories and
      the underappreciated role of wild herbivores.
AB  - Methane is an important greenhouse gas, but characterizing production by source
      sector has proven difficult. Current estimates suggest herbivores produce ~20%
      (~76-189 Tg yr(-1) ) of methane globally, with wildlife contributions uncertain.
      We develop a simple and accurate method to estimate methane emissions and
      reevaluate production by wildlife. We find a strikingly robust relationship
      between body mass and methane output exceeding the scaling expected by
      differences in metabolic rate. Our allometric model gives a significantly better
      fit to empirical data than IPCC Tier 1 and 2 calculations. Our analysis suggests
      that (i) the allometric model provides an easier and more robust estimate of
      methane production than IPCC models currently in use; (ii) output from wildlife
      is much higher than previously considered; and (iii) because of the allometric
      scaling of methane output with body mass, national emissions could be reduced if
      countries favored more, smaller livestock, over fewer, larger ones. 

PMID- 25970852
TI  - Presence of starch enhances in vitro biodegradation and biocompatibility of a
      gentamicin delivery formulation.
AB  - The effect of alpha-amylase degradation on the release of gentamicin from starch
      conjugated chitosan microparticles was investigated up to 60 days. Scanning
      electron microscopic observations showed an increase in the porosity and surface
      roughness of the microparticles as well as reduced diameters. This was confirmed
      by 67% weight loss of the microparticles in the presence of alpha-amylase. Over
      time, a highly porous matrix was obtained leading to increased permeability and
      increased water uptake with possible diffusion of gentamicin. Indeed, a faster
      release of gentamicin was observed with alpha-amylase. Starch-conjugated chitosan
      particles are non-toxic and highly biocompatible for an osteoblast (SaOs-2) and
      fibroblast (L929) cell line as well as adipose-derived stem cells. When
      differently produced starch-conjugated chitosan particles were tested, their
      cytotoxic effect on SaOs-2 cells was found to be dependent on the crosslinking
      agent and on the amount of starch used.

PMID- 25970854
TI  - Octopus-inspired robotics. Preface.

PMID- 25970853
TI  - A combination of doxycycline and ribavirin alleviated chikungunya infection.
AB  - Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV)
      outbreaks have led to significant impact on health care in the developing world.
      Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and
      other common antiviral agents against CHIKV. Our results showed that within the
      TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory
      effect against CHIKV replication in Vero cells. On the other hand, in the
      antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV
      replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects
      were also higher than all but DOXY within the TETRA derivatives group. Docking
      studies of DOXY to viral cysteine protease and E2 envelope protein showed non
      competitive interaction with docking energy of -6.6+/-0.1 and -6.4+/-0.1 kcal/mol
      respectively. The 50% effective concentration (EC50) of DOXY and RIBA was
      determined to be 10.95+/-2.12 MUM and 15.51+/-1.62 MUM respectively, while
      DOXY+RIBA (1:1 combination) showed an EC50 of 4.52+/-1.42 MUM. When compared,
      DOXY showed higher inhibition of viral infectivity and entry than RIBA. In
      contrast however, RIBA showed higher inhibition against viral replication in
      target cells compared to DOXY. Assays using mice as animal models revealed that
      DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity
      in vivo. Further experimental and clinical studies are warranted to investigate
      their potential application for clinical intervention of CHIKV disease. 

PMID- 25970855
TI  - On-chip passive three-port circuit of all-optical ordered-route transmission.
AB  - On-chip photonic circuits of different specific functions are highly desirable
      and becoming significant demands in all-optical communication network.
      Especially, the function to control the transmission directions of the optical
      signals in integrated circuits is a fundamental research. Previous schemes, such
      as on-chip optical circulators, are mostly realized by Faraday effect which
      suffers from material incompatibilities between semiconductors and magneto
      optical materials. Achieving highly functional circuits in which light circulates
      in a particular direction with satisfied performances are still difficult in pure
      silicon photonics platform. Here, we propose and experimentally demonstrate a
      three-port passive device supporting optical ordered-route transmission based on
      silicon thermo-optic effect for the first time. By injecting strong power from
      only one port, the light could transmit through the three ports in a strict order
      (1->2, 2->3, 3->1) while be blocked in the opposite order (1->3, 3->2, 2->1). The
      blocking extinction ratios and operation bandwidths have been investigated in
      this paper. Moreover, with compact size, economic fabrication process and great
      extensibility, this proposed photonic integrated circuit is competitive to be
      applied in on-chip all-optical information processing systems, such as path
      priority selector. 

PMID- 25970856
TI  - Effect of pH and oxygen on biofilm formation in acute otitis media associated
      NTHi clinical isolates.
AB  - OBJECTIVES/HYPOTHESIS: Biofilms occur in animal models of acute otitis media
      (AOM) and in children with recurrent AOM (rAOM) and chronic otitis media with
      effusion (OME). We therefore studied the ability of nontypeable Haemophilus
      influenzae (NTHi) strains from children to form biofilms in vitro under
      conditions we presumed occurred in the middle ear during AOM, rAOM, and OME.
      STUDY DESIGN: Evaluate NTHi isolates for biofilm formation across a pH range
      under aerobic, microaerophilic, and anaerobic conditions. METHODS: Using a
      crystal violet biofilm assay we studied 12 NTHi pediatric clinical isolates to
      investigate biofilm formation over a pH range of 4.5 to 10 under aerobic,
      microaerophilic, and anaerobic conditions. RESULTS: Our findings included: 1) not
      all clinical NTHi strains form biofilms (75% did); 2) the pH of middle ear fluid
      collected from AOM (n = 170; age range, 4-36 months), rAOM (n = 54; age range, 7
      36 months), and OME (n = 30; age range, 9-60 months) subjects tested immediately
      after withdrawal was similar (mean = 8.0;range 7.0-9.0); 3) biofilms formed
      optimally at pH 8.0, a finding that is consistent with previous studies by other
      investigators; 4) biofilms did not form under aerobic conditions as likely occurs
      in AOM, whereas under microaerophilic and anaerobic conditions biofilm formation
      was observed as likely occurs during rAOM and OME. CONCLUSIONS: We concluded that
      biofilm formation by NTHi does not occur in all strains, occurs best where the pH
      = 8.0 and in anaerobic conditions as likely occurs in children during rAOM and
      OME. However, biofilm formation is limited or absent under aerobic conditions as
      likely occurs during AOM. LEVEL OF EVIDENCE: NA.

PMID- 25970857
TI  - Stereotypical reaching movements of the octopus involve both bend propagation and
      arm elongation.
AB  - The bend propagation involved in the stereotypical reaching movement of the
      octopus arm has been extensively studied. While these studies have analyzed the
      kinematics of bend propagation along the arm during its extension, possible
      length changes have been ignored. Here, the elongation profiles of the reaching
      movements of Octopus vulgaris were assessed using three-dimensional
      reconstructions. The analysis revealed that, in addition to bend propagation, arm
      extension movements involve elongation of the proximal part of the arm, i.e., the
      section from the base of the arm to the propagating bend. The elongations are
      quite substantial and highly variable, ranging from an average strain along the
      arm of -0.12 (i.e. shortening) up to 1.8 at the end of the movement (0.57 +/-
      0.41, n = 64 movements, four animals). Less variability was discovered in an
      additional set of experiments on reaching movements (0.64 +/- 0.28, n = 30
      movements, two animals), where target and octopus positions were kept more
      stationary. Visual observation and subsequent kinematic analysis suggest that the
      reaching movements can be broadly segregated into two groups. The first group
      involves bend propagation beginning at the base of the arm and propagating
      towards the arm tip. In the second, the bend is formed or present more distally
      and reaching is achieved mainly by elongation and straightening of the segment
      proximal to the bend. Only in the second type of movements is elongation
      significantly positively correlated with the distance of the bend from the
      target. We suggest that reaching towards a target is generated by a combination
      of both propagation of a bend along the arm and arm elongation. These two motor
      primitives may be combined to create a broad spectrum of reaching movements. The
      dynamical model, which recapitulates the biomechanics of the octopus muscular
      hydrostatic arm, suggests that achieving the observed elongation requires an
      extremely low ratio of longitudinal to transverse muscle force (<0.0016 for an
      average strain along the arm of around 0.5). This was not observed and moreover
      such extremely low value does not seem to be physiologically possible. Hence the
      assumptions made in applying the dynamic model to behaviors such as static arm
      stiffening that leads to arm extension through bend propagation and the patterns
      of activation used to simulate such behaviors should be modified to account for
      movements combining bend propagation and arm elongation.

PMID- 25970859
TI  - Letter to the editor: posterior hyaloid removal.

PMID- 25970860
TI  - Clinic design for a modern retina practice.

PMID- 25970858
TI  - Endoscopic transmucosal direct puncture sclerotherapy for management of airway
      vascular malformations.
AB  - OBJECTIVES/HYPOTHESIS: To describe a multidisciplinary approach to the treatment
      of airway vascular malformations (venous or lymphatic) with direct suspension
      rigid laryngoscopy and direct puncture transmucosal bleomycin sclerotherapy
      injected under road-mapping fluoroscopic monitoring, supplemented by Dyna
      computed tomography utilization. STUDY DESIGN: Case series. METHODS: We performed
      a retrospective medical record and imaging review of four patients with venous
      malformations or lymphatic malformations located in the airway. Patients were
      treated with a combination of direct suspension laryngoscopy or rigid
      nasopharyngoscopy and image-guided direct puncture bleomycin sclerotherapy.
      RESULTS: Two patients presented to our institution with extensive lymphatic
      malformation of the neck, parapharyngeal, and retropharyngeal spaces, and two
      presented with venous malformation of the nasopharynx and oropharynx. All
      patients were treated with multiple sclerotherapy and debulking procedures before
      undergoing combined direct transmucosal puncture bleomycin sclerotherapy guided
      by direct laryngoscopy or nasopharyngoscopy. All patients had complete resolution
      of disease while maintaining a safe airway. CONCLUSIONS: A multidisciplinary
      approach to airway vascular malformations with a combination of endoscopy and
      direct puncture bleomycin sclerotherapy was demonstrated to be a safe and
      effective treatment in our patient cohort. Direct laryngoscopy and
      nasopharyngoscopy provide easy access to the nasopharynx, oropharynx, retro-
      and/or parapharyngeal spaces and larynx. Unlike traditional agents, bleomycin
      induces minimal edema and therefore is an ideal substance to treat airway
      lesions.

PMID- 25970861
TI  - Comparison of Geographic Atrophy Growth Rates Using Different Imaging Modalities
      in the COMPLETE Study.
AB  - BACKGROUND AND OBJECTIVE: To compare the measurements and growth rates of
      geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
      obtained using different imaging modalities. PATIENTS AND METHODS: Thirty
      patients with AMD and GA measuring from 1.25 mm2 to 18 mm2 based on spectral
      domain optical coherence tomography (SD-OCT) fundus imaging were enrolled.
      Imaging was performed at baseline and at follow-up months 3, 6, 9, and 12,
      including autofluorescence (AF) imaging with a fundus camera-based flash system
      (TRC-50DX; Topcon Medical Systems, Oakland, NJ; AF excitation lambda: 535-585 nm;
      detection lambda: 605-715 nm), AF and fluorescein angiography (FA) imaging with a
      confocal scanning laser ophthalmoscopy (SLO) system (Spectralis; Heidelberg
      Engineering, Heidelberg, Germany; AF excitation lambda: 488 nm; detection lambda:
      > 500 nm), and SD-OCT en face imaging (Cirrus; Carl Zeiss Meditec, Dublin, CA).
      RESULTS: Average baseline square root measurements and enlargement rates of
      square root areas appeared similar across all modalities; 0.2 mm was the largest
      difference between any pair of measurement means. The intraclass correlation
      coefficients (ICC) were essentially equal to 1 for all comparisons of area
      measurements but were lower for growth rates than area measurements. Comparison
      of 26-week average enlargement rates showed no significant difference between the
      SLO AF image and enhanced SD-OCT en face image (mean difference: 0.01 mm; SD:
      0.10; P = .70). CONCLUSION: Agreement among all imaging modalities in measuring
      the areas of GA at baseline diminished when the growth rates of GA were compared
      over 26 weeks, likely because each imaging technique identifies different
      anatomic features along the border of GA, which may appear similar but change at
      different rates.

PMID- 25970862
TI  - Punctate hyperfluorescent spots associated with polypoidal choroidal vasculopathy
      on indocyanine green angiography.
AB  - BACKGROUND AND OBJECTIVE: To evaluate punctate hyperfluorescent spots on
      indocyanine green angiography (ICGA) in eyes with polypoidal choroidal
      vasculopathy (PCV). PATIENTS AND METHODS: Retrospective observation case series
      of 88 eyes of 81 patients (63 men and 18 women) analyzing fundus photography,
      fluorescein angiography, ICGA, and spectral-domain optical coherence tomography
      (OCT) findings at baseline. RESULTS: Seven patients (9%) had bilateral PCV
      lesions. Mean age was 68.44 +/- 5.94 years (range: 45 to 86 years). Macular-type
      PCV was found in 72 eyes (81.8%), peripapillary-type PCV in 12 eyes (13.6%), and
      combined-type PCV in four eyes (4.5%). Choroidal vascular hyperpermeability was
      observed in 38 eyes (43.2%), and punctate hyperfluorescent spots on ICGA in 47
      eyes (53.4%). ICGA of unaffected fellow eyes of 74 patients with unilateral PCV
      revealed choroidal hyperpermeability in 23 eyes (31.1%) and punctate
      hyperfluorescent spots in 38 eyes (51.4%). Presence of punctate hyperfluorescent
      spots was significantly associated with choroidal vascular hyperpermeability (P <
      .001). CONCLUSION: Punctate hyperfluorescent spots were frequently observed in
      eyes with PCV in late-phase ICGA, as previously described in eyes with central
      serous chorioretinopathy, which may represent leakage from punctate
      hyperpermeable inner choroid spots or late staining of forme fruste drusen or
      drusen-like subretinal pigment epithelium deposits associated with choroidal
      hyperpermeability.

PMID- 25970863
TI  - Primary intravitreal ranibizumab for high-risk retinopathy of prematurity.
AB  - BACKGROUND AND OBJECTIVE: To evaluate initial treatment of high-risk retinopathy
      of prematurity (ROP) with low-dose intravitreal ranibizumab. PATIENTS AND
      METHODS: Case series of premature infants with high-risk pre-threshold or
      threshold posterior ROP receiving primary therapy with 0.2 mg ranibizumab. Pre
      treatment and post-injection examination, RetCam (Clarity Medical Systems,
      Pleasanton, CA) images, fluorescein angiography, resolution of ROP and plus
      disease, and stability of examinations were assessed. RESULTS: Eight eyes of four
      infants received primary ranibizumab treatment. Plus disease resolved within 48
      hours of unilateral injection, and there was no change in ROP appearance in the
      contralateral eye. Complete resolution of stage 3 ROP occurred 1 week after
      injection. Recurrent progressive stage 2 or 3 ROP in mid to anterior zone 2 was
      noted 8 to 11 weeks after ranibizumab in all eyes. Treatment of recurrent ROP
      with peripheral laser led to complete ROP regression. Comparison of images before
      ranibizumab injection to images after ROP recurred demonstrated anterior retinal
      growth. Retina examinations remained stable without ROP recurrence or detachment
      at follow-up 8 to 18 months after ranibizumab injection. CONCLUSION: Intravitreal
      ranibizumab induces rapid, complete regression of high-risk posterior ROP with
      continued retina growth peripherally. The potential for recurrent ROP after a
      single 0.2 mg ranibizumab injection for posterior ROP requires vigilant
      monitoring. Subsequent peripheral laser for ROP recurrences may spare the
      posterior retina from photocoagulation effects.

PMID- 25970864
TI  - Oral eplerenone for treatment of chronic central serous chorioretinopathy: a case
      series.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the effect of oral eplerenone on subretinal
      fluid, visual acuity, and choroidal thickness in patients with chronic central
      serous chorioretinopathy (CSCR). PATIENTS AND METHODS: Retrospective review of
      all patients (14 eyes of 14 patients) monitored for a minimum of 3 months with
      chronic CSCR who were treated with oral eplerenone in a single multi-physician
      retina practice. Visual acuity, dilated funduscopic examination, and spectral
      domain ocular coherence tomography (OCT) with enhanced depth imaging (EDI) were
      obtained at each visit. Measurement of subfoveal fluid (SFF) height and choroidal
      thickness were performed. Two-tailed paired t test was used to calculate
      statistical significance of pre- and post-treatment variables. RESULTS: At 1
      month, 10 of 14 eyes had decreased SFF height on OCT and two eyes had complete
      resolution of SFF. Mean SFF height decreased from 130 um to 62 um (P = .05). Mean
      choroidal thickness decreased from 315 um to 282 um (P = .07). Mean visual acuity
      improved from logMAR 0.41 to 0.40. At 3 months, 13 of 14 (93%) had decreased SFF
      on OCT, and nine eyes (64%) had complete resolution of SFF. Mean SFF height
      decreased to 21 um (P = .004). Mean choroidal thickness decreased to 253 um (P =
      .10). Mean visual acuity improved to logMAR 0.28 (P = .02). CONCLUSION: Oral
      eplerenone may be effective in treating patients with chronic CSCR.

PMID- 25970865
TI  - Characteristics and outcomes of sequential rhegmatogenous retinal detachments.
AB  - BACKGROUND AND OBJECTIVE: While copious data exist regarding the incidence,
      treatment, and prognosis of rhegmatogenous retinal detachment (RRD), fewer data
      exist regarding bilateral RRD. PATIENTS AND METHODS: The authors performed a
      retrospective review of patients with sequential bilateral rhegmatogenous retinal
      detachments over a 5-year period from January 1, 2009, through December 31, 2014,
      that were repaired at a single institution. Data were reviewed for 80 eyes of 40
      patients, which is the largest series of sequential RRD reported. RESULTS: In
      patients with sequential RRD, the subsequently affected eyes were more likely to
      present with better initial visual acuity, shorter duration of symptoms, less
      macula-off status, and less concurrent proliferative vitreoretinopathy. The
      subsequent eye had better final visual acuity and was less likely to re-detach.
      Subsequent eyes tended to progress to RRD despite prophylactic retinopexy.
      CONCLUSION: The constellation of baseline characteristics in which subsequent
      eyes presented with better initial visual acuity, shorter duration of symptoms,
      less macula-detached status, and less concurrent proliferative vitreoretinopathy
      when compared to the initial eye correspond with the findings that subsequent
      eyes had more successful anatomical and better visual outcomes.

PMID- 25970866
TI  - Retained Intraocular Perfluoro-n-octane After Valved Cannula Pars Plana
      Vitrectomy for Retinal Detachment.
AB  - BACKGROUND AND OBJECTIVE: To investigate cases of retained intraocular perfluoro
      n-octane (PFO) after pars plana vitrectomy (PPV) for retinal detachment (RD).
      PATIENTS AND METHODS: Retrospective, noncomparative case series of six eyes with
      retained intraocular PFO after RD repair. Clinical data were supplemented with an
      experimental silicone eye model. RESULTS: A cluster of six cases of retained
      intraocular PFO after PPV for RD repair were noted shortly after transitioning to
      valved cannulas. PFO was noted in the anterior chamber (AC) and/or vitreous and
      removed with AC paracentesis, AC wash-out, and/or PPV. A silicone eye model
      demonstrated that PFO levels are maintained anterior to cannula insertion with
      valved cannulas only. CONCLUSION: The authors hypothesize that anterior PFO fill
      using valved cannulas can lead to sequestration within the AC, zonules, ciliary
      sulcus, ciliary teeth, and/or capsular bag. They suggest vigilance in not
      overfilling PFO, particularly when transitioning to use of valved cannulas, to
      minimize the risk of intraocular retention.

PMID- 25970867
TI  - Chronic pain management: foreword.

PMID- 25970868
TI  - Chronic pain management: evaluation of chronic pain.
AB  - Chronic pain (CP) is a heterogeneous group of conditions classified as
      neuropathic, muscular, visceral, inflammatory, or mixed. The pathogenesis is not
      completely understood, but neuroanatomic changes and central sensitization, in
      which the central nervous system amplifies pain transmission, are associated
      maladaptations. When treating a patient with CP, first classify the type of pain,
      if possible; assess its intensity; and assess its influence on health, well
      being, and comorbidities. Then develop a treatment plan. At each visit,
      clinicians should assess analgesia (pain level/relief), affect (mood assessment),
      and activities of daily living (functional status); obtain a pill count, if
      appropriate; optimize adjuvant therapy; and evaluate for adverse effects and
      aberrant drug-related behavior. Accurate documentation of behavioral indicators
      of pain, responses to interventions, and management strategies is extremely
      important in facilitating continuity of care and patient safety. 

PMID- 25970869
TI  - Chronic pain management: nonpharmacological therapies for chronic pain.
AB  - Nonpharmacologic therapies have become a vital part of managing chronic pain
      (CP). Although these can be used as stand-alone therapies, nonpharmacologic
      treatments often are used to augment and complement pharmacologic treatments (ie,
      multimodal therapy). Nonpharmacologic approaches can be classified as behavioral,
      cognitive, integrative, and physical therapies. Core principles in developing a
      treatment plan are explaining the nature of the CP condition, setting appropriate
      goals, and developing a comprehensive treatment approach and plan for adherence.
      Clinicians should become familiar with these interventions so that they can offer
      patients flexibility in the pain management approach. Effective noninvasive
      treatment modalities for CP include behavioral therapy for short-term pain
      relief; cognitive behavioral therapy for reducing long-term pain and disability;
      hypnosis as adjunctive therapy; guided imagery, diaphragmatic breathing, and
      muscle relaxation, especially for cancer-related pain; mindfulness-based stress
      reduction for patients with chronic low back pain; acupuncture for multiple pain
      conditions; combination manipulation, manual therapy, endurance exercise,
      stretching, and strengthening for chronic neck pain; animal-assisted therapy; and
      S-adenosyl-L-methionine for joint pain. Guidelines for use of these treatment
      modalities are based on expert panel recommendations in combination with data
      from randomized controlled trials. 

PMID- 25970870
TI  - Chronic pain management: pharmacotherapy for chronic pain.
AB  - Clinicians should combine nonpharmacologic therapies and pharmacotherapy for
      management of chronic pain. Safety and effectiveness determine the choice of
      therapy. Typically, nonopioid analgesics are first-line treatment, including
      acetaminophen, nonsteroidal anti-inflammatory drugs, and topical drugs. A trial
      of an opioid, in combination with other modalities, should be considered if pain
      persists. Because of the potential for serious adverse effects, opioids should be
      prescribed only if the clinician is familiar with their use and associated risks.
      If pain is not controlled, consider pharmacogenetic effects or the addition of
      adjuvant therapy. In states with prescription drug monitoring programs,
      clinicians must access these programs regularly when prescribing a controlled
      substance. Consider performing pill counts and random urine drug screening for
      monitoring drug use. Adjuvant drugs to be considered include antidepressants,
      buspirone, anticonvulsants, muscle relaxants, onabotulinumtoxinA, clonidine, and
      corticosteroids, depending on type of pain and individual characteristics. 

PMID- 25970871
TI  - Chronic pain management: legal and licensure issues.
AB  - Legal and licensure issues are an inevitable aspect of treating patients with
      chronic pain. Clinicians need to ensure compliance with state medical board and
      federal guidelines. Prescription drug abuse continues to be a significant
      problem. Despite the legalization of medical marijuana in some states, there is
      currently no medical indication for prescribing marijuana; the exceptions are
      dronabinol and nabilone. These are approved by the Food and Drug Administration
      for chemotherapy-induced nausea and vomiting, and dronabinol also is approved for
      anorexia in patients with AIDS or cancer. Other legal issues concern
      establishment of chronic pain as a basis for disability status. Clinicians often
      are asked to provide a letter or assessment, such as a functional capacity
      evaluation, for documenting disability. Referral to a physical medicine and
      rehabilitation subspecialist or physical therapist for this evaluation should be
      considered. Balancing legal and licensure issues with the best interests of the
      patient can be challenging for clinicians. 

PMID- 25970873
TI  - [Nonselective beta blockers in decompensated cirrhosis: when to start and for how
      long?].

PMID- 25970872
TI  - [Atypical image of focal nodular hyperplasia: central defect on hepatobiliary
      phase of liver magnetic resonance imaging].

PMID- 25970874
TI  - Medicaid benefit designs for newly eligible adults: state approaches.
AB  - The Affordable Care Act gives states the option of providing less-generous
      Medicaid coverage to adults who become eligible through the law's expansion of
      the program. Based on a review of the benefit design choices made by states that
      had expanded Medicaid by the end of 2014, we find that states have chosen to
      offer more generous coverage than what is required under federal law, either
      narrowing or eliminating the distinction between coverage levels for newly
      eligible adults and those for traditional adult beneficiaries, such as pregnant
      women, parents and guardians, or beneficiaries with disabilities. This suggests
      that states view the newly eligible beneficiaries as having the elevated health
      and health care needs that are common among low-income populations.

PMID- 25970876
TI  - What health care reform means for your tax return: the latest on what to watch
      for--and what to do.

PMID- 25970875
TI  - Implementing the Affordable Care Act: state regulation of marketplace plan
      provider networks.
AB  - Health plans with relatively narrow provider networks have generated widespread
      debate, mainly concerning the level of regulatory oversight necessary to ensure
      plans provide consumers meaningful access to care. The Affordable Care Act
      creates the first federal standard for network adequacy in the commercial
      insurance market for plans offered through the law's insurance marketplaces.
      However, states continue to play a primary role in setting and enforcing network
      rules. This brief examines state network adequacy standards for marketplace plans
      in the 50 states and District of Columbia. We identify state requirements in
      effect at the outset of marketplace coverage, focusing on quantitative measures
      of network sufficiency and rules designed to ensure the delivery of accurate and
      timely provider directories. We then explore the extent to which those standards
      evolved for 2015. Though regulatory changes were limited in year one, states were
      most likely to act to promote network transparency and enhance oversight.

PMID- 25970877
TI  - Shelling out for health insurance...but still not getting full coverage.

PMID- 25970879
TI  - [Discussion about the non-existence of schizophrenia; is there an elephant in the
      room?].

PMID- 25970878
TI  - Supramolecular nesting of cyclic polymers.
AB  - Advances in template-directed synthesis make it possible to create artificial
      molecules with protein-like dimensions, directly from simple components. These
      synthetic macromolecules have a proclivity for self-organization that is
      reminiscent of biopolymers. Here, we report the synthesis of monodisperse cyclic
      porphyrin polymers, with diameters of up to 21 nm (750 C-C bonds). The ratio of
      the intrinsic viscosities for cyclic and linear topologies is 0.72, indicating
      that these polymers behave as almost ideal flexible chains in solution. When
      deposited on gold surfaces, the cyclic polymers display a new mode of two
      dimensional supramolecular organization, combining encapsulation and nesting; one
      nanoring adopts a near-circular conformation, thus allowing a second nanoring to
      be captured within its perimeter, in a tightly folded conformation. Scanning
      tunnelling microscopy reveals that nesting occurs in combination with stacking
      when nanorings are deposited under vacuum, whereas when they are deposited
      directly from solution under ambient conditions there is stacking or nesting, but
      not a combination of both.

PMID- 25970880
TI  - [Research on symmetrical optical waveguide based surface plasmon resonance
      sensing with spectral interrogation].
AB  - Surface plasmon resonance (SPR) sensors with spectral interrogation can adopt
      fiber to transmit light signals, thus leaving the sensing part separated, which
      is very convenient for miniaturization, remote-sensing and on-site analysis.
      Symmetrical optical waveguide (SOW) SPR has the same refractive index of the-two
      buffer media layers adjacent to the metal film, resulting in longer propagation
      distance, deeper penetration depth and better performance compared to
      conventional SPR In the present paper, we developed a symmetrical optical,
      waveguide (SOW) SPR sensor with wavelength interrogation. In the system, MgF2-Au
      MgF2 film was used as SOW module for glucose sensing, and a fiber based light
      source and detection was used in the spectral interrogation. In the experiment, a
      refractive index resolution of 2.8 x 10(-7) RIU in fluid protocol was acquired.
      This technique provides advantages of high resolution and could have potential
      use in compact design, on-site analysis and remote sensing.

PMID- 25970881
TI  - [Research on ground scenery spectral radiation source with tunable spectra].
AB  - A spectrum-tunable ground scenery spectrum radiation source, using LEDs and
      bromine tungsten lamp as luminescence media, was introduced. System structure and
      control of the spectrum radiation source was expounded in detail. In order to
      simulate various ground scenery spectrum distribution with different shapes, a
      ground scenery spectral database was established in the control system. An
      improved genetic algorithm was proposed, and a large number of ground scenery
      spectra were produced by the simulator. Spectral similarity and the average
      spectral matching error of several typical ground scenery spectra were further
      analyzed. Spectral similarity of red bands, green bands, blue bands and near
      infrared spectral band also was discussed. When the radiance of the target was 50
      W x (m2 x sr)(-1), the average spectral matching error was less than 10% and
      spectral similarity was greater than 0.9, up to 0.983. Spectral similarity of red
      band, green band, blue band and near-infrared band (especially green band and
      near-infrared band) was less than that of full-band. Compared with blue band and
      red band, spectral similarity of green band and near-infrared band low-amplitude
      maximum can rearch 50%. Ground scenery spectrum radiation source can be used as
      radiometric calibration source for optical remote sensor, and calibration error,
      which is caused by objectives and calibration sources spectral mismatch, can be
      effectively reduced.

PMID- 25970882
TI  - [The auto-focusing remote laser-induced breakdown spectroscopy system].
AB  - The present paper presents an auto-focus laser-induced breakdown spectroscopy
      (LIBS) remote measuring system. This system contains a Schwarzschild telescope,
      which consists of a convex mirror and a concave mirror. The two spherical mirrors
      are coaxially placed. The convex mirror is mounted on a motorized linear
      translation stage. With this motorized linear translation stage, the convex
      mirror can move along the optical axis to change the spacing between the convex
      mirror and the concave mirror. Therefore the focal length can be adjusted to
      focus the laser on samples at different distances and collect the plasma spectra.
      The advantages of the telescope system include, firstly, the light path of laser
      focusing and spectra signal collection is the same, which make it easier for
      mounting and collimation; secondly, the light path of the telescope uses total
      reflection type, which is fit for the detection in ultra-violate region; finally,
      the telescope consists of only two spherical mirrors which are relatively easier
      to manufacture. Within the translation range of the motorized linear translation
      stage, the focal length of the telescope in this paper can be adjusted from 1.5
      to 3.6 m. The diameter of the focusing spot varies from 0.5 to 1.0 mm. Utilizing
      this telescope system, LIBS experiments were conducted using copper sample. And
      the characteristic lines of Cu element (Cu I 223.01 nm, Cu I 224.43 nm) obtained
      are used for the auto focusing. By investigating the relation of the area of
      spectral lines covered and the spacing between the mirrors, the optimal laser
      focusing location was obtained. The LIBS experiment results show that the system
      functions well, fulfilling the demand of remote ablation of sample and LIBS
      spectral measuring, and the telescope is able to auto-focus the laser on samples
      at different position to perform remote LIBS experiment.

PMID- 25970883
TI  - [The research on separating and extracting overlapping spectral feature lines in
      LIBS using damped least squares method].
AB  - In recent years, the technology of laser induced breakdown spectroscopy has been
      developed rapidly. As one kind of new material composition detection technology,
      laser induced breakdown spectroscopy can simultaneously detect multi elements
      fast and simply without any complex sample preparation and realize field, in-situ
      material composition detection of the sample to be tested. This kind of
      technology is very promising in many fields. It is very important to separate,
      fit and extract spectral feature lines in laser induced breakdown spectroscopy,
      which is the cornerstone of spectral feature recognition and subsequent elements
      concentrations inversion research. In order to realize effective separation,
      fitting and extraction of spectral feature lines in laser induced breakdown
      spectroscopy, the original parameters for spectral lines fitting before iteration
      were analyzed and determined. The spectral feature line of' chromium (Cr I :
      427.480 nm) in fly ash gathered from a coal-fired power station, which was
      overlapped with another line(FeI: 427.176 nm), was separated from the other one
      and extracted by using damped least squares method. Based on Gauss-Newton
      iteration, damped least squares method adds damping factor to step and adjust
      step length dynamically according to the feedback information after each
      iteration, in order to prevent the iteration from diverging and make sure that
      the iteration could converge fast. Damped least squares method helps to obtain
      better results of separating, fitting and extracting spectral feature lines and
      give more accurate intensity values of these spectral feature lines: The spectral
      feature lines of chromium in samples which contain different concentrations of
      chromium were separated and extracted. And then, the intensity values of
      corresponding spectral lines were given by using damped least squares method and
      least squares method separately. The calibration curves were plotted, which
      showed the relationship between spectral line intensity values and chromium
      concentrations in different samples. And then their respective linear
      correlations were compared. The experimental results showed that the linear
      correlation of the intensity values of spectral feature lines and the
      concentrations of chromium in different samples, which was obtained by damped
      least squares method, was better than that one obtained by least squares method.
      And therefore, damped least squares method was stable, reliable and suitable for
      separating, fitting and extracting spectral feature lines in laser induced
      breakdown spectroscopy.

PMID- 25970884
TI  - [Near-infrared quantum cutting downconversion luminescence of Yb3+ ion
      cooperative energy transferred from YVO4 matrix donor].
AB  - The present manuscript researches the near infrared quantum cutting luminescence
      phenomena of Yb3+ ion in YVO4 crystal matrix The luminescence spectra, excitation
      spectra and fluorescence lifetimes were measured. It was found that the
      excitation of YVO4 crystal matrix energy band by 322.0 nm light can result in the
      effective secondary cooperative energy transfer of Yba+ ion from the YVO4 crystal
      matrix It results in the intense 985.5 nm 2F(5/2)-->?2F(7/2) near infrared
      quantum cutting luminescence of Yb3+ ion. Meanwhile, the 430.O nm luminescence
      intensity of YVO4 crystal matrix decreases greatly. From the experimental
      measurements, it was found that the lifetime of 430.0 nm fluorescence of (A)
      Yb(1.5) : YVO4 crystal is tauA = 3.785 s and that of (B) YVO4 crystal is
      tauB=22.72 s. It was found also that the theoretical efficiency up limit of
      quantum cutting of (A) Yb(1.5) : YVO4 crystal is about eta1.5%=183-3%.

PMID- 25970885
TI  - [The impact of ZnS/CdS composite window layer on the quantun efficiency of CdTe
      solar cell in short wavelength].
AB  - ZnS/CdS composite window layer was prepared by magnetron sputtering method and
      then applied to CdTe solar cell. The morphology and structure of films were
      measured. The data of I-V in light and the quantum efficiency of CdTe solar cells
      with different window layers were also measured. The effect of ZnS films prepared
      in different conditions on the performance of CdTe solar cells was researched.
      The effects of both CdS thickness and ZnS/CdS composite layer on the transmission
      in short wavelength were studied. Particularly, the quantum efficiency of CdTe
      solar cells with ZnS/CdS window layer was measured. The results show as follows.
      With the thickness of CdS window layer reducing from 100 to 50 nm, the
      transmission increase 18.3% averagely in short wavelength and the quantum
      efficiency of CdTe solar cells increase 27.6% averagely. The grain size of ZnS
      prepared in 250 degrees C is smaller than prepared at room temperature. The
      performance of CdTe solar cells with ZnS/CdS window layer is much better if ZnS
      deposited at 250 degrees C. This indicates grain size has some effect on the
      electron transportation. When the CdS holds the same thickness, the transmission
      of ZnS/CdS window layer was improved about 2% in short wavelength compared with
      CdS window layer. The quantum efficiency of CdTe solar cells with ZnS/CdS window
      layer was also improved about 2% in short wavelength compared with that based on
      CdS window layer. These indicate ZnS/CdS composite window layer can increase the
      photon transmission in short wavelength so that more photons can be absorbed by
      the absorbent layer of CdTe solar cells.

PMID- 25970887
TI  - [Er3+:Yb3+ co-doped nanocrystals BaGd2ZnO5 of up-conversion optical temperature
      sensing].
AB  - By far, the most efficient upconversion nanocrystals luminescence materials
      BaGd2ZnO5: 4%Yb3+ , 1%Er3+, with stable chemical performance, were prepared by
      using Sol-gel method. XRD pattern shows that the sample is pure phase, belongs to
      the orthogonal crystals, and space group is Pbnm; SEM micrograph shows that the
      prepared sample of the morphology sized around 150 nm is evenly distributed.
      Samples with 971 nm semiconductor laser excitation produce a strong green
      emission, visible to the naked eye, and uponversion strength and pump energy
      relation n = 1.22 is two-photon for the realization of the upconversion emission.
      They originated from Er3+ ions 2H(11/2)--2H(11/2)-->4I(15/2) and 4S(3/2)-
      >4I(15/2) transition emission, Er3+ ions main excited state absorption (ESA)
      process is: 4I(15/2)-->4I(11/2)-->2F(7/2)-->2H(11/2), 4S(3/2), Yb3+ was added
      because of its large absorption cross section (10(4) cm(-1)) so that it is easy
      to transfer excitation energy to the E3+ ions which enhance the layout particles
      number and the energy state of the 1F7/2, thereby enhancing the intensity of the
      peaks of the spectrum. Fluorescence intensity ratio (FIR) technique based on the
      green upconversion emission of the sample has been studied because the Er3+ ions
      2H(11/2) and 4S(3/2) energy level spacing is small. The electrons at the two
      levels conform to the Boltzmann distribution which is a function of temperature,
      and thus the fluorescence intensity ratio of two levels can be used to measure
      the temperature of the substrate material. This method does not interfere with
      temperature field of the measured object, and can eliminate the uncertainty of
      the accuracy; the test has a wide temperature range and reasonable temperature
      resolution, the pump source used is simple, convenient and inexpensive, and has
      more commercial values. The temperature range of the samples is from 350 to 800
      K, and the highest temperature measuring sensitivity can reach 0.0031 K(1). At
      the same time, under low excitation density, it can produce higher conversion
      transmission power, making it become ideal material for distance non-contact
      temperature measurement.

PMID- 25970886
TI  - [Three photons quantum-cutting system on the rear surface of cells to improve the
      efficiencies of solar cells].
AB  - The authors present a solar cell model with a three photons quantum-cutting
      system on the rear surface, then the method of calculation of limiting
      efficiencies was used to get the maximum efficiency 58.58% at the band gap
      Eg=0.9315 eV, and in contrast with two-photons quantum-cutting system, it is
      greatly improved. The result can prove that the three-photons quantum-cutting has
      a great sense to improve the efficiencies of solar cells. It is the exciting
      development for us to find out the useful luminescence materials to get the high
      efficiency.

PMID- 25970888
TI  - Synthesis and spectroscopy of silica nanoparticles as scatter centers in random
      gain porous media.
AB  - This work was carried out to synthesis a silica matrix by sol-gel technique,
      which used as host to Kiton Red laser dye doped with silica nanoparticles, which
      also prepared by sol-gel technique, to obtain KR-SiO2 nanoparticles confined in
      silica xerogel matrix. The rods at different pH values were successfully
      synthesized. The different values of pH cause different size of obtained
      nanoparticles, these nanoparticles act as scatter centers in the matrix.
      Amplified spontaneous emission (ASE), threshold pumping energy (E(th)), and mean
      free path (l(t)) for photons in the rods have been reported. the results show
      that the values of bandwidth at full width half-maximum (FWHM) and the threshold
      energy are about 8.7 nm and 12 mJ respectively.

PMID- 25970889
TI  - Determination of minimum enzymatic decolorization time of reactive dye solution
      by spectroscopic & mathematical approach.
AB  - Synthetic dyes are very important for textile dyeing, paper printing, color
      photography and petroleum products. Traditional methods of dye removal include
      biodegradation, precipitation, adsorption, chemical degradation, photo
      degradation, and chemical coagulation. Dye decolorization with enzymatic reaction
      is an important issue for several research field (chemistry, environment) In this
      study, minimum decolorization time of Remazol Brilliant Blue R dye with
      Horseradish peroxidase enzyme was calculated using with mathematical equation
      depending on experimental data. Dye decolorization was determined by monitoring
      the absorbance decrease at the specific maximum wavelength for dye. All
      experiments were carried out with different initial dye concentrations of Remazol
      Brilliant Blue R at 25 degrees C constant temperature for 30 minutes. The
      development of the least squares estimators for a nonlinear model brings about
      complications not encountered in the case of the linear model. Decolorization
      times for completely removal of dye were calculated according to equation. It was
      shown that mathematical equation was conformed exponential curve for dye
      degradation.

PMID- 25970890
TI  - [Advances of NIR spectroscopy technology applied in seed quality detection].
AB  - Near infrared spectroscopy (NIRS) technology developed fast in recent years, due
      to its rapid speed, less pollution, high-efficiency and other advantages. It has
      been widely used in many fields such as food, chemical industry, pharmacy,
      agriculture and so on. The seed is the most basic and important agricultural
      capital goods, and seed quality is important for agricultural production. Most
      methods presently used for seed quality detecting were destructive, slow and
      needed pretreatment, therefore, developing one kind of method that is simple and
      rapid has great significance for seed quality testing. This article reviewed the
      application and trends of NIRS technology in testing of seed constituents, vigor,
      disease and insect pests etc. For moisture, starch, protein, fatty acid and
      carotene content, the model identification rates were high as their relative
      contents were high; for trace organic, the identification rates were low as their
      relative content were low. The heat-damaged seeds with low vigor were
      discriminated by NIRS, the seeds stored for different time could also been
      identified. The discrimination of frost-damaged seeds was impossible. The NIRS
      could be used to identify health and infected disease seeds, and did the
      classification for the health degree; it could identify parts of the fungal
      pathogens. The NIRS could identify worm-eaten and health seeds, and further
      distinguished the insect species, however the identification effects for small
      larval and low injury level of insect pests was not good enough. Finally, in
      present paper existing problems and development trends for NIRS in seed quality
      detection was discussed, especially the single seed detecting technology which
      was characteristic of the seed industry, the standardization of its spectral
      acquisition accessories will greatly improve its applicability.

PMID- 25970891
TI  - [Study on estimation of deserts soil total phosphorus content from thermal
      infrared emissivity].
AB  - Soil phosphorus provides nutrient elements for plants, is one of important
      parameters for evaluating soil quality. The traditional method for soil total
      phosphorus content (STPC) measurement is not effective and time-consuming.
      However, remote sensing (RS) enables us to determine STPC in a fast and efficient
      way. Studies on the estimation of STPC in near-infrared spectroscopy have been
      developed by scholars, but model accuracy is still poor due to the low absorption
      coefficient and unclear absorption peak of soil phosphorus in near-infrared. In
      order to solve the deficiency which thermal-infrared emissivity estimate desert
      soil total phosphorus content, and could improve precision of estimation deserts
      soil total phosphorus. In this paper, characteristics of soil thermal-infrared
      emissivity are analyzed on the basis of laboratory processing and spectral
      measurement of deserts soil samples from the eastern Junggar Basin. Furthermore,
      thermal-infrared emissivity based RS models for STPC estimation are established
      and accuracy assessed. Results show that: when STPC is higher than 0.200 g x kg(
      1), the thermal-infrared emissivity increases with the increase of STPC on the
      wavelength between 8.00 microm and 13 microm, and the emissivity is more
      sensitive to STPC on the wavelength between 9.00 and 9.6 microm; the estimate
      mode based on multiple stepwise regression was could not to estimate deserts soil
      total phosphorus content from thermal-infrared emissivity because the estimation
      effects of them were poor. The estimation accuracy of model based on partial
      least squares regression is higher than the model based on multiple stepwise
      regression. However, the accuracy of second-order differential estimation model
      based on partial least square regression is higher than based on multiple
      stepwise regression; The first differential of continuous remove estimation model
      based on partial least squares regression is the best model with R2 of correction
      and verification are up to 0.97 and 0.82 respectively, and RMSE of correction and
      verification are only 0.0106 and 0.015 7 respectively, RPD is 2.62. Research
      results provide optimized models for remotely sensed analysis on deserts soil
      total phosphorus content and could realize timeliness and effective monitoring on
      the space-time dynamic of deserts soil total phosphorus content for future
      regional ecological restoration.

PMID- 25970892
TI  - Determining the Zn content of cherry in field using VNIR spectroscopy.
AB  - Visible and near-infrared (VNIR) spectroscopy is an eco-friendly method used for
      estimating plant nutrient deficiencies. The aim of this study was to investigate
      the possibility of using VNIR method for estimating Zn content in cherry orchard
      leaves under field conditions. The study was conducted in 3 different locations
      in Isparta region of Turkey. Fifteen cherry orchards containing normal and Zn
      deficient plants were chosen, and 60 leaf samples were collected from each
      location. The reflectance spectra of the leaves were measured with an ASD
      FieldSpec HandHeld spectroradiometer and a plant probe. The Zn contents of leaf
      samples were predicted through laboratory analysis. The spectral reflectance
      measurements were used to estimate the Zn levels using stepwise multiple linear
      regression analysis method. Prediction models were created using the highest
      coefficient of determination value. The results show that Zn content of cherry
      trees can be estimated using the VNIR spectroscopic method (87.5<r2<96.79).
      Moreover, plant nutrient contents can be estimated without using chemicals.
      However, further research is necessary to develop a standard method for field
      conditions. Because spectral reflectance is affected by ecological conditions,
      agricultural applications and nutrient interactions, more effective models must
      be developed depending on the geographical location, period and plant type.

PMID- 25970893
TI  - [Apply fourier transform infrared spectra coupled with two-dimensional
      correlation analysis to study the evolution of humic acids during composting].
AB  - The composition and structure of humic acids formed during composting play an
      important influence on the quality and mature of compost. In order to explore the
      composition and evolution mechanism, municipal solid wastes were collected to
      compost and humic and fulvic acids were obtained from these composted municipal
      solid wastes. Furthermore, fourier transform infrared spectra and two-dimensional
      correlation analysis were applied to study the composition and transformation of
      humic and fulvic acids during composting. The results from fourier transform
      infrared spectra showed that, the composition of humic acids was complex, and
      several absorbance peaks were observed at 2917-2924, 2844-2852, 2549, 1662, 1622,
      1566, 1454, 1398, 1351, 990-1063, 839 and 711 cm(-1). Compared to humic acids,
      the composition of fulvci acids was simple, and only three peaks were detected at
      1725, 1637 and 990 cm(-1). The appearance of these peaks showed that both humic
      and fulvic acids comprised the benzene originated from lignin and the
      polysaccharide. In addition, humic acids comprised a large number of aliphatic
      and protein which were hardly detected in fulvic acids. Aliphatic,
      polysaccharide, protein and lignin all were degraded during composting, however,
      the order of degradation was different between humic and fulvci acids. The result
      from two-dimensional correlation analysis showed that, organic compounds in humic
      acids were degraded in the following sequence: aliphatic> protein> polysaccharide
      and lignin, while that in fulvic acids was as following: protein> polysaccharide
      and aliphatic. A large number of carboxyl, alcohols and ethers were formed during
      the degradation process, and the carboxyl was transformed into carbonates. It can
      be concluded that, fourier transform infrared spectra coupled with two
      dimensional correlation analysis not only can analyze the function group
      composition of humic substances, but also can characterize effectively the
      degradation sequence of these groups and identified the formation mechanism and
      dynamics of humic substances during composting.

PMID- 25970894
TI  - [Identification and classification of disease severity of wheat stripe rust using
      near infrared spectroscopy technology].
AB  - Wheat stripe rust caused by Puccinia striiformis f. sp. tritici, is an
      economically important disease in the world. It is of great significance to
      assess disease severity of wheat stripe rust quickly and accurately for
      monitoring and controlling the disease. In this study, wheat leaves infected with
      stripe rust pathogen under different severity levels were acquired through
      artificial inoculation in artificial climate chamber. Thirty wheat leaves with
      disease severity equal to 1%, 5%, 10%, 20%, 40%, 60%, 80% or 100% were picked
      out, respectively, and 30 healthy leaves were chosen as controls. A total of 270
      wheat leaves were obtained and then their near infrared spectra were measured
      using MPA spectrometer. According to disease severity levels, 270 near infrared
      spectra were divided into 9 categories and each category included 30 spectra.
      From each category, 7 or 8 spectra were randomly chosen to make up the testing
      set that included 67 spectra. The remaining spectra were treated as the training
      set. A qualitative model for identification and classification of disease
      severity of wheat stripe rust was built using near infrared reflectance
      spectroscopy (NIRS) technology combined with discriminant partial least squares
      (DPLS). The effects of different preprocessing methods of obtained spectra,
      ratios between training sets and testing sets, and spectral ranges on qualitative
      recognition results of the model were investigated. The optimal model based on
      DPLS was built using cross verification method in the spectral region of 4000
      9000 cm(-1) when "centralization" was used as the preprocessing method of spectra
      and the spectra were divided into the training set and the testing set with the
      ratio equal to 3:1. Accuracy rate of the training set was 95.57% and accuracy
      rate of the testing set was 97.01%. The results showed that good recognition
      performance could be acquired using the model based on DPLS. The results
      indicated that the method using near infrared reflectance spectroscopy technology
      proposed in this study is feasible for identification and classification of
      disease severity of wheat stripe rust. A new method was provided for monitoring
      and assessment of wheat stripe rust.

PMID- 25970895
TI  - [Near-infrared spectra combining with CARS and SPA algorithms to screen the
      variables and samples for quantitatively determining the soluble solids content
      in strawberry].
AB  - In using spectroscopy to quantitatively or qualitatively analyze the quality of
      fruit, how to obtain a simple and effective correction model is very critical for
      the application and maintenance of the developed model. Strawberry as the
      research object, this research mainly focused on selecting the key variables and
      characteristic samples for quantitatively determining the soluble solids content.
      Competitive adaptive reweighted sampling (CARS) algorithm was firstly proposed to
      select the spectra variables. Then, Samples of correction set were selected by
      successive projections algorithm (SPA), and 98 characteristic samples were
      obtained. Next, based on the selected variables and characteristic samples, the
      second variable selection was performed by using SPA method. 25 key variables
      were obtained. In order to verify the performance of the proposed CARS algorithm,
      variable selection algorithms including Monte Carlo-uninformative variable
      elimination (MC-UVE) and SPA were used as the comparison algorithms. Results
      showed that CARS algorithm could eliminate uninformative variables and remove the
      collinearity information at the same time. Similarly, in order to assess the
      performance of the proposed SPA algorithm for selecting the characteristic
      samples, SPA algorithm was compared with classical Kennard-Stone algorithm
      Results showed that SPA algorithm could be used for selection of the
      characteristic samples in the calibration set. Finally, PLS and MLR model for
      quantitatively predicting the SSC (soluble solids content) in the strawberry were
      proposed based on the variables/samples subset (25/98), respectively. Results
      show that models built by using the 0.59% and 65.33% information of original
      variables and samples could obtain better performance than using the ones
      obtained by using all information of the original variables and samples. MLR
      model was the best with R(pre)2 = 0.9097, RMSEP=0.3484 and RPD = 3.3278.

PMID- 25970896
TI  - [Attenuated total reflection-fourier transform infrared spectroscopic study of
      dried shark fin products].
AB  - Sixty-four pieces of shark fin dried products (including real, fake and
      artificial shark fin products) and real products coated with gelatin were rapidly
      and nondestructively analyzed by attenuated total reflection-Fourier transform
      infrared spectroscopy (ATR-FTIR). The characteristic of IR spectrograms among the
      above four kinds of samples were systematically studied and comparied, the
      results showed that the spectrograms of the same kind of samples were repeatable,
      and different kinds of shark fin products presented significant differences in
      the spectrograms, which mainly manifested as the specific absorption peaks of
      amido bonds in protein (1650, 1544 cm(-1)) and skeletal vibration in
      polysaccharide (1050 cm(-1)). The spectrograms of real shark fins were
      characterized by the strong absorption peaks of protein characteristic amide I
      and II absorbent (1650, 1544 cm(-1)) and relatively weak C--O--C vibration
      absorbent (1050 cm(-1)) owing to the high content of protein and relatively low
      level of polysaccharide. For fake shark fin products that were molded form by
      mixing together with the offcut of shark, collagen and other substances, the
      introduction of non-protein materials leaded to the weaker amido bonds absorbent
      than real products along with a 30 cm(-1) blue shift of amide I absorbent.
      Opposite to the real sample, the relatively strong absorption peak of
      polysaccharide (approximately 1047 cm(-1)) and barely existed amide absorbent
      were the key features of the spectrogram of artificial samples, which was
      synthersized by polysaccharide like sodium alginate. Real samples coated with
      gelatin, the peak strength of protein and polysaccharide were decreased
      simultaneously when the data collection was taken at the surface of sample, while
      the spectrogram presented no significant difference to real samples when the data
      was collected in the section. The results above indicated that by analyzing the
      characteristic of IR spectrograms and the value range of Apro/Apol collected by
      ATR-FTIR method could perform the undamaged and rapid identification for shark
      fins.

PMID- 25970897
TI  - [Effect of pH on circular dichroism and Raman spectroscopy of secondary structure
      of beta-casein from Chinese human milk].
AB  - To obtain a structural basis for the beta-casein in Chinese human milk,
      structural transitions of the beta-casein in response to variation of pH were
      investigated using Raman and circular dichroism (CD) spectroscopy. Both methods
      indicated that the secondary structures of beta-casein in the solution were
      induced by the pH. Secondary structural analysis of beta-casein by CD
      spectroscopy yielded 0.5%-2% alpha-helical, 16%-18% beta-sheet, 30%-34% beta-turn
      and 49%-51% random coil contents. Another result was that as pH increases, these
      structures change. Several distinct transitions were observed by circular
      dichroism in alpha-helix at pH 8 and pH 10. Raman spectrum also showed random
      coil as the major secondary structure in native beta-casein, for the
      characteristic band of the beta-casein amide I was at 1662 cm(-1): Calculations
      from I850/I830 suggested that the tyrosine residues of beta-casein tended to
      "exposure". CD and Raman spectra both showed that at neutral and alkaline pH the
      beta-casein existed predominantly in random coil conformation, and the proportion
      of alpha-helix was higher at pH 8 than under other pH conditions. Over the range
      of pH studied, the sheet and turn areas remained relatively constant, and in the
      condition of pH 8, the content of alpha-helical was higher than in the other pH
      conditions.

PMID- 25970898
TI  - [Quantitative analysis of thiram by surface-enhanced raman spectroscopy combined
      with feature extraction Algorithms].
AB  - Three feature extraction algorithms, such as the principal component analysis
      (PCA), the discrete cosine transform (DCT) and the non-negative factorization
      (NMF), were used to extract the main information of the spectral data in order to
      weaken the influence of the spectral fluctuation on the subsequent quantitative
      analysis results based on the SERS spectra of the pesticide thiram. Then the
      extracted components were respectively combined with the linear regression
      algorithm--the partial least square regression (PLSR) and the non-linear
      regression algorithm--the support vector machine regression (SVR) to develop the
      quantitative analysis models. Finally, the effect of the different feature
      extraction algorithms on the different kinds of the regression algorithms was
      evaluated by using 5-fold cross-validation method. The experiments demonstrate
      that the analysis results of SVR are better than PLSR for the non-linear
      relationship between the intensity of the SERS spectrum and the concentration of
      the analyte. Further, the feature extraction algorithms can significantly improve
      the analysis results regardless of the regression algorithms which mainly due to
      extracting the main information of the source spectral data and eliminating the
      fluctuation. Additionally, PCA performs best on the linear regression model and
      NMF is best on the non-linear model, and the predictive error can be reduced
      nearly three times in the best case. The root mean square error of cross
      validation of the best regression model (NMF+SVR) is 0.0455 micormol x L(-1) (10(
      6) mol x L(-1)), and it attains the national detection limit of thiram, so the
      method in this study provides a novel method for the fast detection of thiram. In
      conclusion, the study provides the experimental references the selecting the
      feature extraction algorithms on the analysis of the SERS spectrum, and some
      common findings of feature extraction can also help processing of other kinds of
      spectroscopy.

PMID- 25970899
TI  - [Research on volatiles of rakkyo (Allium Chinense G. Don) and Chinese chive
      (Allium Tuberosum Rottl. ex Sprengel) based on headspace and the molecular
      recognition of SERS].
AB  - The head space and the molecular recognition of surface enhanced Raman scattering
      (SERS) were used to research volatiles of rakkyo and Chinese chive. Their
      volatiles SERS spectra were obtained using nano-silver colloid as the substrate.
      Then, volatiles SERS spectra of rakkyo and Chinese Chive were compared
      respectively with the volatiles SERS spectra of liquid allyl methyl sulfide, 1
      propanethiol, diallyl disulfide and all possible pairings of the three compounds.
      The results showed that the repeatability of volatiles SERS spectra of rakkyo and
      Chinese Chive were all good. The volatiles SERS spectrum of rakkyo was basically
      consistent with the volatiles SERS spectrum of the mixture of liquid allyl methyl
      sulfide and 1-propanethiol. The volatiles SERS spectrum of rakkyo included both
      characteristic peaks at 626 and 674 cm(-1) in volatiles SERS spectrum of allyl
      methyl sulfide and characteristic peaks at 702, 893, 1024,1085, 1215 and 1320 cm(
      1) in volatiles SERS spectrum of 1-Propanethiol. The volatiles SERS spectrum of
      Chinese chive was basically consistent with the volatiles SERS spectrum of the
      mixture of liquid allyl methyl sulfide and diallyl disulfide. The volatiles SERS
      spectrum of Chinese chive included both characteristic peak at 674 cm(-1) in
      volatiles SERS spectrum of allyl methyl sulfide and characteristic peaks at 407,
      577, 716, 1189, 1291 and 1401 cm(-1) in volatiles SERS spectrum of diallyl
      disulfide. These illustrated that volatiles of rakkyo contained allyl methyl
      sulfide and 1-Propanethiol and volatiles of Chinese chive contained allyl methyl
      sulfide and diallyl disulfide. The volatiles of rakkyo and Chinese chive were
      different, but they all contained allyl methyl sulfide. All of the above have
      revealed that the headspace combined with molecular recognition of SERS can be
      directly used to study volatiles of rakkyo and Chinese chive. The technology
      under room temperature, can guarantee the volatiles obtained were the primitive
      constituents in plant volatiles. By comparison with the standard sample, the
      constituents in plant volatiles can be determined.

PMID- 25970900
TI  - [Component analysis of the circulating fluid in an adsorption tower in a P-xylene
      unit based on raman spectral decomposition].
AB  - In order to achieve fast and accurate online analysis of the circulating fluid in
      an adsorption tower in a p-xylene unit, the Raman spectral analysis method is
      adopted. However, the Raman spectra of the pure components included in the
      circulating fluid overlap together, and the concentration of each component
      varies obviously, the present Raman analysis technology needs a large amount of
      training samples. Therefore, this paper applies Raman spectral decomposition
      method in component analysis of the circulating fluid. First of all, the Raman
      spectra of the pure components and the spectra of a few training samples must be
      measured, and baseline subtraction and mean normalization are applied to obtain
      pretreated Raman spectra. Then the characteristic wave number range, 680-880 cm(
      1), is chosen, and the Raman spectral decomposition method is adopted, to get
      decomposition coefficients of each component for each training sample. Next, the
      mathematical model between coefficients and concentrations of each component are
      built based on all training samples. For a testing sample, the above spectral
      pretreatment and the spectral decomposition for the same wave number range is
      adopted, then the decomposition coefficients of each component can be obtained.
      Based on the built mathematical model, the concentrations of all components can
      be predicted. Experimental results show that the standard prediction errors for
      the concentration of toluene, ethylbenzene, p-xylene, m-xylene, o-xylene and p
      diethylbenzene are 0.301%, 0.088%, 0.563%, 0.384%, 0.366% and 0.536%
      respectively. The above method provides a methodological basis for the online
      analysis of the circulating fluid in adsorption towers.

PMID- 25970901
TI  - [Surface-enhanced Raman spectroscopy analysis of thiabendazole pesticide].
AB  - Surface-enhanced Raman spectroscopy (SERS) technique was used to analyze the
      Raman peaks of thiabendazole pesticides in the present paper. Surface enhanced
      substrates of silver nanoparticle were made based on microwave technology. Raman
      signals of thiabendazole were collected by laser Micro-Raman spectrometer with
      514. 5 and 785 nm excitation wavelengths, respectively. The Raman peaks at
      different excitation wavelengths were analyzed and compared. The Raman peaks 782
      and 1 012 at 785 nm excitation wavelength were stronger, which were C--H out-of
      plane vibrations. While 1284, 1450 and 1592 cm(-1) at 514.5 nm excitation
      wavelength were stronger, which were vng and C==N stretching. The study results
      showed that the intensity of Raman peak and Raman shift at different excitation
      wavelengths were different And strong Raman signals were observed at 782, 1012,
      1284, 1450 and 1592 cm(-1) at 514.5 and 785 nm excitation wavelengths. These
      characteristic vibrational modes are characteristic Raman peaks of carbendazim
      pesticide. The results can provide basis for the rapid screening of pesticide
      residue in agricultural products and food based on Raman spectrum.

PMID- 25970902
TI  - [Effect of temperature on the aggregation behavior of collagen solution by two
      dimensional synchronous fluorescence correlation spectroscopy].
AB  - The synchronous fluorescence spectroscopy and two dimensional correlation
      analysis method were applied to study the aggregation behavior of acid-soluble
      collagen solutions (0.2, 0.4 and 1.6 mg x mL(-1)) during the heating process of
      10-70 degrees C. It was found that the fluorescence excited at 292 and 282 nm
      (delta lamda=9 nm) belongs to the tyrosine (Tyr) residues which participate in
      forming hydrogen bonds or not, respectively. The two dimensional correlation
      analysis with the temperature varying showed that with the temperature increased
      (10-30 degrees C) hydrogen bonds among collagen molecular with Tyr residues
      formed in the 0.2 mg x mL(-1) collagen solution, while the higher aggregations of
      collagen molecular and hydrophobic micro-domains appeared in the 0.4 and 1.6 mg x
      mL(-1) collagen solutions. With approaching the denatured temperature of collagen
      (36-38 degrees C), the hydrophobic micro-domain and aggregates seemed to be
      broken in the 0.4 and 1.6 mg x mL(-1) collagen solutions, however the hydrogen
      bonds in the 0.2 mg x mL(-1) were stable. Above the denaturation temperature of
      collagen, the triple-helix structure of collagen molecular in solution of each
      concentration tended to be loose. In the heating process of 45-70 degrees C, this
      trend was more obvious.

PMID- 25970903
TI  - Study on fluorescence spectra of chlorothalonil residues and the interaction
      between chlorothalonil and Chinese herbal medicines.
AB  - The fluorescence spectrum was studied for the chlorothalonil (0.2928 mg x mL(-1))
      using spectrofluorophotometer. The experiment results showed that the
      characteristic peaks (352 and 366 nm) are found in the spectrum of chlorothalonil
      standard solution when the excitation wavelength is 320 nm. And it was found that
      the shoulder peak gradually disappeared at 366 nm, while the fluorescence peak is
      stable at 352 nm with the decline of the solution concentration The exponential
      functional relationship between the concentration of chlorothalonil and
      fluorescence intensity at 352 nm was obtained, and its correlation coefficient is
      0.999. The experimental results are consistent with the theoretical formula about
      fluorescence intensity and concentration The prediction model functions were also
      obtained through the liner fitting to the chlorothalonil solution of low
      concentration, and the correlation coefficient is 0. 995. The limit of detection
      (LOD) is 0.0188 microg x mL(-1), the limit of quantification (LOQ) is 0.0627
      microg x mL(-1), and the linear range is 0.0627-28.45 microg x mL(-1). And
      fluorescence spectra were studied for the mixed system of astragalus, medlar and
      chlorothalonil. It was found that the fluorescence intensity of chlorothalonil
      solution is all declined with the addition of two kinds of Chinese Herbal
      Medicines, which indicates that there is an interaction between them. The decay
      rate of fluorescence intensity was obtained which is 88.5% and 99.7%,
      respectively. Then the model functions were established between fluorescence
      intensity and the volume of addition, and the correlation coefficient is 0.994
      and 0.997, respectively. This study provides the experimental foundation for the
      detection of chlorothalonil residues using fluorescence spectrum. It is shown
      that it is possible to detect pesticide residues of chlorothalonil using
      fluorescence spectra directly, and the relevant parameter value satisfied the
      requirement of testing standard. Therefore there is an important value for
      further detecting the pesticide residues in fruit juice using fluorescence
      spectrum. It was also found that the fluorescence intensity of chlorothalonil is
      decreased with the addition of astragalus or medlar, which provides the new
      research approach to studying the pesticide degradation using medicinal and
      edible Chinese Herbal Medicines.

PMID- 25970904
TI  - [Effect of quantum dots CdSe/ZnS's concentration on its fluorescence].
AB  - The authors measured the absorption and the fluorescence spectra of the quantum
      dots CdSe/ZnS with 4 nm in size at different concentration with the use of the UV
      Vis absorption spectroscopy and fluorescence spectrometer. The effect of quantum
      dots CdSe/ZnS's concentration on its fluorescence was especially studied and its
      physical mechanism was analyzed. It was observed that the optimal concentration
      of the quantum dots CdSe/ZnS for fluorescence is 2 micromole x L(-1). When the
      quantum dot's concentration is over 2 micromol x L(-1), the fluorescence is
      decreased with the increase in the concentration. While the quantum dot's
      concentration is less than 2 micromol x L(-1), the fluorescence is decreased with
      the decrease in the concentration. There are two main reasons: (1) fluorescence
      quenching and 2) the competition between absorption and fluorescence. When the
      quantum dot's concentration is over 2 micromol x L(-1), the distance between
      quantum dots is so close that the fluorescence quenching is induced. The closer
      the distance between quantum dots is, the more serious the fluorescence quenching
      is induced. Also, in this case, the absorption is so large that some of the
      quantum dots can not be excited because the incident light can not pass through
      the whole sample. As a result, the fluorescence is decreased with the increase in
      the quantum dot's concentration. As the quantum dot's concentration is below 2
      micromol x L(-1), the distance between quantum dots is far enough that no more
      fluorescence quenching is induced. In this case, the fluorescence is determined
      by the particle number per unit volume. More particle number per unit volume
      produces more fluorescence. Therefore, the fluorescence is decreased with the
      decrease in the quantum dot's concentration.

PMID- 25970905
TI  - [Study on the concentration of mineral oil in water by online intelligent
      detection based on fluorescence spectrum].
AB  - In order to monitor the oil pollution of water real time and accurately for the
      environmental protection, an intelligent online detection system for the mineral
      oil in water is put forward in the present paper, based on the technology of
      ultraviolet fluorescence and internet of things (IOT). For this system, the
      resolution can be improved by using the higher precision asymmetric Czemy-Turner
      monochromator; the impact of light fluctuations on the results of exploration can
      be corrected by a bunch reference light; the optical system deviation caused by
      the instrument vibration can be reduced by optical fiber transmission; the
      coupling efficiency of fiber and output signal can be increased by a special
      fiber beam; the real-time measurement, data processing and remote control can be
      achieved by the control module and wireless communication module. This system has
      characteristics of high integration, high precision and good stability etc. The
      concentration of the unknown sample can be accurately calculated by the methods
      of parallel algorithms of chemometric metrology and the calculation errors caused
      by different components can be reduced by the theory of chemical correction
      factor analysis. The fluorescence spectra of three kinds of sample solution,
      diesel, engine and crude oil in preparative concentration of 10, 25, 50 and 100
      mg x L(-1) were measured by this system respectively. The absorption wavelengths
      of the above-mentioned three oils were measured to be 256, 365 and 397 nm by a
      grating spectrometer; their absorbances were measured to be 0.028, 0.036 and
      0.041 by fluorescence spectrophotometer, respectively. Their fluorescence
      emission wavelengths are 355, 419 and 457 nm respectively. Finally the
      concentration detection limits of the mineral oil in water of diesel, engine and
      crude oil were obtained, i.e., 0.03, 0.04 and 0.06 mg x L(-1) respectively. Their
      relative errors are 2.1%, 1.0% and 2.8% respectively.

PMID- 25970906
TI  - [STR fluorescence spectral analysis based on matrix analysis].
AB  - In a detection system of STR labeled by multiple fluorescence, the overlaps do
      occur between the different colored fluorophores owing to the band broadening
      characteristic of the employed fluorescence spectrum. It is crucial to obtain
      effective energy distribution specific for different wavelengths so as to improve
      the utilization efficiency of fluorescence intensity. To reach this goal in
      practice, we propose a data processing method based on matrix analysis. Firstly,
      a spectral calibration must be done for STR fluorescence spectral analysis, and
      then a emission spectral distribution of each colored fluorophore excitated by
      laser is created from the detection signal. And then, the matrix normalization is
      computed from the above fixed spectrum distribution. And lastly, the inversion of
      the correct matrix is used to get the resolved and desirable STR spectrogram. In
      addition, performance evaluation shows that this method based on matrix analysis
      can make use of the fluorescence spectrum energy of each wavelength and resolve
      the overlapping spectrum effectively.

PMID- 25970907
TI  - [Derivative fluorescence probe recognition results of the light physical
      mechanism of metal ions].
AB  - As people deeply study the electronic spectra of fluorescent compounds and
      photophysical behavior, enormous progress has been made in the aspect of changes
      and states of different systems in the use of fluorescent molecules as probes.
      PTC-DA is a kind of typical fluorescent molecular probe that is highly sensitive
      and selective in water environment. This paper makes a research on the physical
      mechanism of light of PTCDA by TDF (Density Functional Theory), calculates the
      optimal configuration the charge population and excitation spectra of PTCDA
      molecules under ideal condition and acquires PTCDA fluorescence emission spectra
      then analyses that PTCDA is a kind of quenching and dual colorimetric signal
      probe response. Its optical signal response mechanism belongs to ICT
      (Intramolecular Charge Transfer) mechanism. According to the results, this
      perylene derivatives is fitted with Cu2+ excited state absorption spectra. Before
      and after the combination with Cu2+, the peak shape of absorption spectrum is
      similar. When copper is added, the overall absorption peak position occurred
      redshift, quenching discoloration happens. By comparing with experimental values,
      the calculated molecular configuration is reasonable and effective and the peak
      of excitation spectra is realistic. Analysis shows that: PTCDA molecules divalent
      copper ions have better fluorescence detection activity, the optical signal
      response mechanisms are intramolecular charge transfer (ICT) mechanisms. When a
      molecule receives divalent copper ions, the absorption spectrum peak position
      redshifts, intramolecular charge transfer direction and intensity changes. There
      occur both quenching signal and discoloration signal. It is a kind of fluorescent
      probe material with double quenching and discoloration fluorescent signal, which
      has great potential for development. This paper makes an early-stage exploration
      of the physical mechanism of light response mechanism analysis in molecular
      fluorescent probe field and can be a systematically valuable theoretical
      reference for this field.

PMID- 25970908
TI  - [Early warning for various internal faults of GIS based on ultraviolet
      spectroscopy].
AB  - As the basis of accurate diagnosis, fault early-warning of gas insulation
      switchgear (GIS) focuses on the time-effectiveness and the applicability. It
      would be significant to research the method of unified early-warning for partial
      discharge (PD) and overheated faults in GIS. In the present paper, SO2 is
      proposed as the common and typical by-product. The unified monitoring could be
      achieved through ultraviolet spectroscopy (UV) detection of SO2. The derivative
      method and Savitzky-Golay filtering are employed for baseline correction and
      smoothing. The wavelength range of 290-310 nm is selected for quantitative
      detection of SO2. Through UV method, the spectral interference of SF6 and other
      complex by-products, e.g., SOF2 and SOF2, can be avoided and the features of
      trace SO2 in GIS can be extracted. The detection system is featured by compacted
      structure, low maintenance and satisfactory suitability in filed surveillance. By
      conducting SF6 decomposition experiments, including two types of PD faults and
      the overheated faults between 200-400 degrees C, the feasibility of proposed UV
      method has been verified. Fourier transform infrared spectroscopy and gas
      chromatography methods can be used for subsequent fault diagnosis. The different
      decomposition features in two kinds of faults are confirmed and the diagnosis
      strategy has been briefly analyzed. The main by-products under PD are SOF2 and
      SO2F2. The generated SO2 is significantly less than SOF2. More carbonous by
      products will be generated when PD involves epoxy. By contrast, when the material
      of heater is stainless steel, SF6 decomposes at about 300 "C and the main by
      products in overheated faults are SO2 and SO2F2. When heated over 350 degrees C,
      SO2 is generated much faster. SOz content stably increases when the GIS fault
      lasts. The faults types could be preliminarily identified based on the generation
      features of SO2.

PMID- 25970909
TI  - [Pattern recognition of decorative papers with different visual characteristics
      using visible spectroscopy coupled with principal component analysis (PCA)].
AB  - As one of the most important decorative materials for the modern household
      products, decorative papers impregnated with melamine not only have better
      decorative performance, but also could greatly improve the surface properties of
      materials. However, the appearance quality (such as color-difference evaluation
      and control) of decorative papers, as an important index for the surface quality
      of decorative paper, has been a puzzle for manufacturers and consumers. Nowadays,
      human eye is used to discriminate whether there exist color difference in the
      factory, which is not only of low efficiency but also prone to bring subjective
      error. Thus, it is of great significance to find an effective method in order to
      realize the fast recognition and classification of the decorative papers. In the
      present study, the visible spectroscopy coupled with principal component analysis
      (PCA) was used for the pattern recognition of decorative papers with different
      visual characteristics to investigate the feasibility of visible spectroscopy to
      rapidly recognize the types of decorative papers. The results showed that the
      correlation between visible spectroscopy and visual characteristics (L*, a* and
      b*) was significant, and the correlation coefficients wereup to 0.85 and some was
      even more than 0. 99, which might suggest that the visible spectroscopy reflected
      some information about visual characteristics on the surface of decorative
      papers. When using the visible spectroscopy coupled with PCA to recognize the
      types of decorative papers, the accuracy reached 94%-100%, which might suggest
      that the visible spectroscopy was a very potential new method for the rapid,
      objective and accurate recognition of decorative papers with different visual
      characteristics.

PMID- 25970910
TI  - [Spectrum characteristics of leaching components from co-contaminated loess in ex
      situ column washing reaction].
AB  - Soil contamination is regarded as one of the most serious issues to humanity all
      over the world. It is statistically believed that over one-fifth of the farmland,
      that is 20 million ha, is found to be contaminated by heavy metals in China. And
      the related issues, caused by soil contamination, of food safety, human health
      and eco-environmental quality attract much attention by public with more serious
      contamination than before. The technological approach for soil remediation is
      widely investigated. The technology of soil washing is effective for contaminants
      removal, while the treatment procedure might lead to component leaching from soil
      system, harmful for soil fertility, physicochemical properties and ecological
      functions. The study of spectral characteristics on leaching component is
      significant for decision-making of contaminated sites remediation and ecological
      function recovery, while the related investigation seems weaker nowadays. The
      paper mainly revealed the leaching characteristics of component from Pb/Cd
      contaminated loess in the washing process with Ethylene Diamine Tetraacetic Acid
      (EDTA) in reaction column, and the research objectives included base cations,
      loess nutrients, clay minerals and organic matter. The variation of clay minerals
      was analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM),
      and 3D-EEM fluorescence spectrum was used for the identification of dissolved
      organic matter (DOM). The experimental results showed: the leaching component
      from loess is detected in the washing reaction. The final removal efficiency (240
      min) of Pb and Cd from loess are 49. 86% and 62.25%, respectively. The sodium
      ions and nitrate nitrogen are the most easily leaching component, and little
      difference of clay minerals is identified before and after washing reaction. The
      fulvic acid-like (FA-like) material was firstly (10 min) detected around E(ex/em)
      = 240-250/320-340 and E(ex/em) = 260-290/450-470 in 3D-EEM fluorescence spectrum,
      and the humin acid-like (HA-like, E(ex/em) = 290-320/430-490) appeared at 60 min
      with weaker fluorescence intensity of FA-like (E(ex/em) = 240/320). The decreased
      fluorescence intensity of FA-like and HA-like, shown after 120 min and 240 min,
      indicated the component variation of DOM in the leaching solution. The
      spectroscopy approach is appropriate for characteristics identification of
      leaching component from co-contaminated loess.

PMID- 25970911
TI  - [Spectroscopic study on film formation mechanism and structure of composite
      silanes-V-Zr passive film].
AB  - A composite silanes-V-Zr passive film was overlayed on hot-dip galvanized steel.
      Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR),
      X-ray photoelectron spectrometer (XPS) and radio frequency glow discharge optical
      emission spectrometry (rf-GD-OES) were used to characterize the molecular
      structure of the silanes-V-Zr passive film. The mechanism of film formation was
      discussed: The results show that the silane molecules are crosslinked as the main
      film former and inorganic inhibitor is even distributed in the film. The fitting
      peak of 100.7 eV in XPS single Si2p energy range spectra of the composite silanes
      V-Zr passive film and the widening and strengthening of the Si--O infrared
      absorption peak at 1100 cm(-1) indicate that the silanes were adsorbed on the
      surface of zinc with chemical bond of Si--O--Zn, and the silane molecules were
      connected with each other by bond of Si--O--Si. Two characteristic absorption
      peaks of amide at 1650 and 1560 cm(-1) appear in the infrared spectroscopy of the
      composite silanes-V-Zr passive film, and a characteristic absorption peak of
      epoxy groups at 910 cm(-1) disappears in the infrared spectroscopy of the passive
      film. The results indicate that gamma-APT can be prepared through nucleophilic
      ring-opening of ethylene oxide in gamma-GPT molecule to form C--N covalent bonds.
      The rf-GD-OES results indicate that there is a oxygen enriched layer in 0.3
      microm depth of the composite silanes-V-Zr passive film. Moreover, ZrF4, ZrO2 and
      some inorganic matter obtained by the reaction during the forming processof the
      composite silanes-V-Zr passive film are distributed evenly throughout the film.
      According to the film composition, the physical processes and chemical reactions
      during the film forming process were studied by using ATR-FTIR. Based on this,
      the film forming mechanism was proposed.

PMID- 25970912
TI  - [Non-covalent albumin conjugates of silicon (IV) phthalocyanines axially
      substituted with nucleoside: preparation and in vitro photodynamic activities].
AB  - The interactions of bovine serum albumin (BSA) with five novel silicon (N)
      phthalocyanines(SiPcl-5) axially modified by nucleosides (cytidine, 5-N-cytidine,
      methyl cytidine, uridine and methyl uridine) derivatives were studied by
      fluorescence spectroscopy. The results show that there are strong interactions
      between these silicon phthalocyanines and BSA with a binding constant of (4.90
      83.18) x 10(5) mol(-1) x L. Therefore, the non-covalent BSA conjugate of bis(2',
      3'-O-isopropyl-cytidine-oxy) phthalocyaninatosilicon(IV) (SiPc1) was further been
      prepared. The molar ratio of phthalocyanine to albumin was found to be 1:1 for
      the obtained SiPcl-BSA conjugate. The absorption spectra of SiPc1 and SiPc1-BSA
      in the visible region have no significant difference, both showing an Q-band
      maximum at about 686 nm. It indicates that the spectroscopic characteristics of
      SiPc1 are not affected by binding to albumin. The SiPcl-BSA conjugate exhibits
      high photodynamic activity against human hepatoma cell line HepG2 with an IC50
      value of 3.0 x 10(-7) mol x L(-1). By comparsion, SiPc1-BSA has a higher
      photodynamic activity than SiPc1 (in PBS formation, IC50 = 7.0 x 10(-7) mol x L(
      1)), which can be attributed to its higher cellular uptake.

PMID- 25970913
TI  - [Preparation and characterization of kaolinite-potassium dihydrogen phosphate
      intercalation composite].
AB  - Thepotassium dihydrogenphospiate (KDP) intercalated kaolinite (K-KDP) was
      prepared by a three-step reaction. Firstly, polar dimethyl sulphoxide (DMSO) was
      introduced into the layers of kaolinite by ultrasonic method and the product K
      DMSO was obtained as precursor; secondly DMSO was replaced by potassium acetate
      (KAc) and the product K-KAc was gotten as intermediate; finally KAc was replaced
      by KDP. The intercalation ratio of the final product K-KDP reached 81.3%. The
      structure of products at differentreaction process was characterized by Fourier
      transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning
      electron microscope (SEM) in detail. FTIR results showed the existence of P==O in
      the final product but moved from 1300 to 1201 cm(-1). XRD results documented that
      the interlayer spacing of kaolinite was enlarged during the whole intercalation
      reaction. SEM indicated that the agglomeration of kaolinite was destroyed and the
      particle size distribution became more uniform.

PMID- 25970914
TI  - [Measurements of IR absorption across section and spectrum simulation of
      lewisite].
AB  - The vapor infrared transmission spectra of varied concentration of lewisite-1
      were measured by a long-path FT-IR spectrometer, and its characteristic
      frequencies are 814, 930, 1563 cm(-1); their infrared absorption cross section
      (a) were determined using Beer-Lambert law. The corresponding sigma values are
      3.89 +/- 0.01, 1.43 +/- 0.06, 4.47 +/- 0.05 ( X 10(-20) cm2 x molecule(-1)). Two
      little teeny peaks, 1158, 1288 cm(-1) were found in the measured spectra. Density
      Functional Theory (DFT) was applied to calculated the infrared spectra of
      lewisite-1, -2, -3 on a b3lyp/6-311+g(d, p) level by Gauss09 package. The
      vibration modes were assigned by Gaussview5. 08. The calculated spectra and
      experimental spectra are in good agreement with each other in 600-1600 cm(-1)
      range, for the Person's r is 0.9991. The calculated spectra also showed three
      characteristic frequencies (293, 360, 374 cm(-1)) related to As atom. 0.977 was a
      scaling factor we determined for lewisite-1 through least-square error and its
      performance to scale lewisite-1, -2, -3 was acceptable. The results of this work
      are useful for monitoring environmental atmospheric concentrations of lewisite.

PMID- 25970915
TI  - [Synthesis of naphthalimide derivatives and its recognition of Fe3+].
AB  - A novel naphthalimide derivatives N-hexyl-4-benzylamino-naphthalimide(HBN) was
      synthesized from 4-bromo-1, 8-naphthalic anhydride, and the structure was
      characterized by NMR and MS. Spectral properties of HBN for recognition of Fe3+
      were investigated by fluorescence spectrum. In a certain range of Fe3+ from 4 x
      10(-7) to 1 x 10(-2) mol x L(-1), the fluorescence intensity of HBN significantly
      reduced with increasing concentration of Fe3+ in ethanol/water (1:1, volume
      ratio). The equation of linear regression was F0/F=623.253 2c(Fe3+) + 0.9642 (R2
      = 0.9963). Moreover, no obvious interference with the detection of the Fe3+ ion
      was observed in the presence of the common metal ions such as Ca2+, Na+, CU2+,
      Zn2+, Pb2+, Co2+, Ni2+, Mn2+ and Fe2+, which indicated that HBN displayed
      excellent selectivity and high sensitivity for the detection of Fe3+.

PMID- 25970916
TI  - [Piezoresistivity of ultra-thin poly-silicon layer by aluminum-induced layer
      exchange].
AB  - Poly-Si film, due to its favorable piezoresistive properties, has been widely
      used in piezoresistive sensors. The previous researches have shown that the ultra
      thin poly-Si film have better piezoresistive properties than common poly-silicon
      film, and have promising future of application. A promising method to obtain
      large grained high quality poly-silicon films by low-temperature crystallization
      of an amorphous precursor material is the aluminum-induced layer exchange
      (ALILE). In this paper, ultra-thin poly-Si films were prepared by aluminum
      induced layer exchange (ALILE). Experimental results of Raman spectroscopy show
      that a narrow and symmetrical Raman peak at the wave number of about 518 cm(-1)
      was observed for all samples, indicating that the films were fully crystallized.
      XRD results show that the crystallites of ultra-thin poly-silicon layer were
      preferably (111) and (220) oriented. Hall affect measurements show that hole
      concentration of the films (p-type) were between 9 x 10(18) and 6 x 10(19) cm(
      3). Restorative properties show that the piezoresistors exhibit gauge factors
      (GFs) up to 60, with temperature coefficients of GF (TCGF) between -0.17-0%
      degree C and temperature coefficients of resistance (TCR) between -0.2 and -0.1%
      degrees C. The study of the ultra-thin poly-Si films by ALILE is completed, and
      the study results lay a foundation for application of the film

PMID- 25970917
TI  - [Research on identification of cabbages and weeds combining spectral imaging
      technology and SAM taxonomy].
AB  - Weeds automatic identification is the key technique and also the bottleneck for
      implementation of variable spraying and precision pesticide. Therefore, accurate,
      rapid and non-destructive automatic identification of weeds has become a very
      important research direction for precision agriculture. Hyperspectral imaging
      system was used to capture the hyperspectral images of cabbage seedlings and five
      kinds of weeds such as pigweed, barnyard grass, goosegrass, crabgrass and setaria
      with the wavelength ranging from 1000 to 2500 nm. In ENVI, by utilizing the MNF
      rotation to implement the noise reduction and de-correlation of hyperspectral
      data and reduce the band dimensions from 256 to 11, and extracting the region of
      interest to get the spectral library as standard spectra, finally, using the SAM
      taxonomy to identify cabbages and weeds, the classification effect was good when
      the spectral angle threshold was set as 0. 1 radians. In HSI Analyzer, after
      selecting the training pixels to obtain the standard spectrum, the SAM taxonomy
      was used to distinguish weeds from cabbages. Furthermore, in order to measure the
      recognition accuracy of weeds quantificationally, the statistical data of the
      weeds and non-weeds were obtained by comparing the SAM classification image with
      the best classification effects to the manual classification image. The
      experimental results demonstrated that, when the parameters were set as 5-point
      smoothing, 0-order derivative and 7-degree spectral angle, the best
      classification result was acquired and the recognition rate of weeds, non-weeds
      and overall samples was 80%, 97.3% and 96.8% respectively. The method that
      combined the spectral imaging technology and the SAM taxonomy together took full
      advantage of fusion information of spectrum and image. By applying the spatial
      classification algorithms to establishing training sets for spectral
      identification, checking the similarity among spectral vectors in the pixel
      level, integrating the advantages of spectra and images meanwhile considering
      their accuracy and rapidity and improving weeds detection range in the full range
      that could detect weeds between and within crop rows, the above method
      contributes relevant analysis tools and means to the application field requiring
      the accurate information of plants in agricultural precision management

PMID- 25970918
TI  - [Prediction of SPAD value in oilseed rape leaves using hyperspectral imaging
      technique].
AB  - In the present work, prediction models of SPAD value (Soil and Plant Analyzer
      Development, often used as a parameter to indicate chlorophyll content) in
      oilseed rape leaves were successfully built using hyperspectral imaging
      technique. The hy perspectral images of 160 oilseed rape leaf samples in the
      spectral range of 380-1030 nm were acquired. Average spectrum was extracted from
      the region of interest (ROI) of each sample. We chose spectral data in the
      spectral range of 500-900 nm for analysis. Using Monte Carlo partial least
      squares(MC-PLS) algorithm, 13 samples were identified as outliers and eliminated.
      Based on the spectral information and measured SPAD values of the rest 147
      samples, several estimation models have been built based on different parameters
      using different algorithms for comparison, including: (1) a SPAD value estimation
      model based on partial least squares(PLS) in the whole wavelength region of 500
      900 nm; (2) a SPAD value estimation model based on successive projections
      algorithmcombined with PLS(SPA-PLS); (3) 4 kind of simple experience SPAD value
      estimation models in which red edge position was used as an argument; (4) 4 kind
      of simple experience SPAD value estimation models in which three vegetation
      indexes R710/R760, (R750-R705)/(R750-R705) and R860/(R550 x R708), which all have
      been proved to have a good relevance with chlorophyll content, were used as an
      argument respectively; (5) a SPAD value estimation model based on PLS using the 3
      vegetation indexes mentioned above. The results indicate that the optimal
      prediction performance is achieved by PLS model in the whole wavelength region of
      500-900 nm, which has a correlation coefficient(r(p)) of 0.8339 and a root mean
      squares error of predicted (RMSEP) of 1.52. The SPA-PLS model can provide avery
      close prediction result while the calibration computation has been significantly
      reduced and the calibration speed has been accelerated sharply. For simple
      experience models based on red edge parameters and vegetation indexes, although
      there is a slight gap between theprediction performance and that of the PLS model
      in the whole wavelength region of 500-900 nm, they also have their own unique
      advantages which should be thought highly of: these models are much simpler and
      thus the calibration computation is reduced significantly, they can perform an
      important function under circumstances in which increasing modeling speed and
      reducing calibration computation operand are more important than improving the
      prediction accuracy, such as the development of portable devices.

PMID- 25970919
TI  - [Photometric micro-titration model of DPPH radicals scavenging activity and its
      application].
AB  - In the present paper, the stoichiometric ratio (R) for the interreaction of DPPH
      radicals with the antoxidant was employed as a evaluation index for DPPH radicals
      scavenging activity of antioxidants. This evaluation index was related only with
      the stoichiometric relationship between DPPH radicals and the antioxidant, not
      the relationship with the initial DPPH amount and the volume of sample, which
      could offer a solution for the problem of poor comparability of EC50 under
      different conditions. A novel photometric micro-titration method was proposed for
      the determination of the stoichiometric ratio (R) for the interreaction of DPPH
      radicals with the antoxidant. The titration equation was established based on the
      absorbance difference (deltaA) of DPPH radicals in the titration process and the
      added amount of antoxidant. The stoichiometric ratio (R) for the reaction of DPPH
      radicals with the addition amount of antoxidant was determined by the titration
      equation obtained, while, the DPPH median elimination concentration (EC50) of
      antoxidant can be calculated by the stoichiometric ratio (R). The above
      photometric micro-titration model was verified using rutin as DPPH radicals
      scavenger. As experiment results, the stoichiometric ratio (R) of DPPH radicals
      to rutin was determined to be in the range of 1.817-1.846. The calculated value
      of EC50 was 1.196 x 10(-3), 2.392 x 10(-3), 4.819 x 10(-3) and 7.292 x 10(-3) mg
      x mL(-1) for 1.12 x 10(-7), 2.24 x 10(-7), 4.48 x 10(-7) and 6.72 x 10(-7) mol of
      the additon amount of DPPH radicals, respectively. The proposed method has better
      precision and reliability with smaller amount of sample than conventional method.
      While, the obtained stoichiometric ratio value (R) of rutin was employed to
      calculate the rutin median elimination concentration for DPPH EC50) according to
      the conditions as reported in the literatures, and the calculated results were
      consistent with that reported in the literatures.

PMID- 25970920
TI  - [The new applications of NMR technology in the field of characterization of
      surface properties of the material].
AB  - Nuclear magnetic resonance (NMR) technology has been developed continuely because
      of its rapid, accurate and high resolution advantages, The technology has become
      an important method to analyze the soil properties, and to identify the structure
      of matters, food analysis, medical imaging fields. This study summarized two
      aspects of the important applications of NMR in the characterization of the
      surface properties of materials. First, the use of NMR techniques for the
      adsorption, desorption and diffusion behaviors of polymer on solid particles
      (mainly SiO2 particles). Sencond, to investigate the wettability and water uptake
      progress of contaminated soils using NMR techniques. This study summarized the
      important applications of NMR techniques in the characterization of surface
      properties. It also showed the unique application in the field of polymer
      materials and environment. This study introduced the measured method for the
      relaxation time of substance using acorn surface area analyzer in the liquid
      environment. It reflect the surface properties and structural features of
      substance. It also provided data support for the explanation of environmental
      behaviors of contaminants and thus, it played an important role in the
      environmental field. Compared to the conventional BET method, acorn surface area
      analyzer showed the advantages in terms of conditions and time measurement.
      Especially, traditional BET method cannot get the information of the specific
      surface area of substances in the liquid directly, but acorn surface area
      analyzer solved the difficult problem. It is a new breakthrough in the field of
      characterization of the surface properties of materials by NMR in the liquid. We
      analyzed the application of acorn surface area analyzer in pharmaceuticals,
      cosmetic materials, electronic products because acorn surface area analyzer could
      reflects the important characteristics of the surface properties and structural
      features of substance. And we provide the prospective of the applications of NMR
      techniques in organic matter of soils, drug and natural products detecting.

PMID- 25970921
TI  - [Selective determination of itraconazole in the presence of its oxidative
      degradation product by a new spectrophotometric method].
AB  - A simple, specific, accurate and precise spectrophotometric stability indicating
      method is developed for determination of itraconazole in the presence of its
      oxidative degradation product and in pharmaceutical formulations. A newly
      developed spectrophotometric method called ratio difference method by measuring
      the difference in amplitudes between 230 and 265 nm of ratio spectra. The
      calibration curve is linear over the concentration range of 5-25 microg x mL(-1)
      with mean percentage recovery of 99.81 +/- 1.002. Selective quantification of
      itraconazole, singly in bulk form, pharmaceutical formulations and in the
      presence of its oxidative degradation product is demonstrated. The results have
      been statistically compared with a pharmacopeial method.

PMID- 25970922
TI  - [Measurement of atomic number of alkali vapor and pressure of buffer gas based on
      atomic absorption].
AB  - High sensitivitymagnetic measurementscanbe achieved by utilizing atomic
      spinmanipulation in the spin-exchange-relaxation-free (SERF) regime, which uses
      an alkali cell as a sensing element. The atomic number density of the alkali
      vapor and the pressure of the buffer gasare among the most important parameters
      of the cell andrequire accurate measurement. A method has been proposed and
      developedto measure the atomic number density and the pressure based on
      absorption spectroscopy, by sweeping the absorption line and fittingthe
      experiment data with a Lorentzian profile to obtainboth parameters. Due to
      Doppler broadening and pressure broadening, which is mainly dominated by the
      temperature of the cell and the pressure of buffer gas respectively, this work
      demonstrates a simulation of the errorbetween the peaks of the Lorentzian profile
      and the Voigt profile caused by bothfactors. The results indicates that the
      Doppler broadening contribution is insignificant with an error less than 0.015%
      at 313-513 K for a 4He density of 2 amg, and an error of 0.1% in the presence of
      0.6-5 amg at 393 K. We conclude that the Doppler broadening could be ignored
      under above conditions, and that the Lorentzianprofile is suitably applied to fit
      the absorption spectrumobtainingboth parameters simultaneously. In addition we
      discuss the resolution and the instability due to thelight source, wavelength and
      the temperature of the cell. We find that the cell temperature, whose uncertainty
      is two orders of magnitude larger than the instability of the light source and
      the wavelength, is one of the main factors which contributes to the error.

PMID- 25970923
TI  - [Characterization of matrix effects in microanalysis of sulfide minerals by laser
      ablation-inductively coupled plasma-mass spectrometry based on an element pair
      method].
AB  - Matrix effect between reference materials and samples is one of the major factors
      affecting the accuracy of analytical results by laser ablation-inductively
      coupled plasma-mass spectrometry (LA-ICP-MS). However, there is no method or
      calculation formula to quantify matrix effect between standards and samples up to
      date. In this paper, the linear correlation coefficient r of the Ii/I(is-Ci)/Cis
      graphs of element pairs were used to characterize the matrix effect, which took
      the ratios of concentrations (ci/ c(is)) and intensities (Ii/Iis) of the
      analytical element and internal standard element as x-axis and gamma-axis,
      respectively. Matrix effects of 6 element pairs in 13 glass reference materials,
      2 sulfide reference materials and 2 sulfide minerals using Fe as internal
      standard was studied, with the linear correlation coefficient r of Fe-Cu, Fe-Zn
      element pairs both less than 0. 999 and trace Fe--Mn, Fe--Co, Fe--Ga, Fe--Pb
      element pairs all better than 0.999. Matrix effects of 3 major element pairs in 2
      sulfide ref- erence materials and 6 sulfide minerals using S as internal standard
      was also studied, with the linear correlation coefficient r of S--Fe, S--Cu, S-
      Zn all less than 0.999. The great majority of relative errors of EMPA analytical
      results for major elements in sulfide minerals were greater than 10%, whether
      analyzed using Fe as internal standard with glass reference materials as external
      standard, or S as internal standard with sulfide reference materials MASS-1, IMER
      1 as external standard, respectively. But the most analytical results for trace
      elements calibrated by glass reference materials using Fe as internal standard
      were well agreed with sulfide standard MASS-1, with the relative errors less than
      15%. The results showed that matrix effects existed in glass reference materials,
      sulfide reference materials and sulfide minerals, and it also proved a certain
      rationality and practicability for quantification of matrix effect using the
      linear correlation coefficient r of the Ii/Iis-Ci/Cis graphs by this element pair
      method. This study also indicated that trace elements in sulfide minerals could
      be calibrated using Fe as internal standard with non-matrix matched glass
      reference materials as external standard, especially for NIST610 contained nearly
      all the trace elements in sulfide minerals and with relative high concentrations
      of each element, which obtained analytical results agreed well with sulfide
      standard MASS-1.

PMID- 25970924
TI  - [Analysis of inorganic elements in hydroponic Taraxacum mongolicum grown under
      different spectrum combinations by ICP-AES].
AB  - Dandelion (Taraxacum mongolicum) was hydroponically cultured in a completely
      enclosed plant factory, in which fluorescence and LED emitting spectra of
      different bands were used as the sole light source for plant growth. Effects of
      spectral component on the growth of dandelion were studied and the contents of
      ten inorganic elements such as K, P, Ca, Mg, Na, Fe, Mn, Zn, Cu and B in
      dandelion were analyzed by ICP-AES technology. The results showed that: (1) Under
      the condition of similar photosynthetic active radiation (PAR), single R or
      combined spectrums of FLRB were beneficial for biomass accumulation, while single
      B was the contrary; (2) Macroelements content ratio in Taraxacum mongolicum grown
      under FLwas K:Ca:P:Mg : Na=79.74:32.39:24.32:10.55:1.00, microelements content
      ratio was Fe:Mn:B:Zn:Cu = 9.28:9.71:3.82:2.08:1.00; (3) Red light (peak at 660
      nm) could promote the absorptions of Ca, Fe, Mn, Zn, while absorption of Cu was
      not closely related to spectral conditions; (4) Thehighest accumulation of Ca,
      Na, Mn and Zn were obtained in aerial parts of Taraxacum mongolicum plants grown
      under pure red spectrum R, while the accumulation of the rest six elements
      reached the highest level under the mixed spectrum FLRB.

PMID- 25970925
TI  - [Standard addition determination of impurities in Na2CrO4 by ICP-AES].
AB  - Coupled plasma atomic emission spectrometry (ICP-AES) was used to determine the
      trace impurities of Ca, Mg, Al, Fe and Si in industrial sodium chromate.
      Wavelengths of 167.079, 393.366, 259.940, 279.533 and 251.611 nm were selected as
      analytical lines for the determination of Al, Ca, Fe, Mg and Si, respectively.
      The analytical errors can be eliminated by adjusting the determined solution with
      high pure hydrochloric acid. Standard addition method was used to eliminate
      matrix effects. The linear correlation, detection limit, precision and recovery
      for the concerned trace impurities have been examined. The effect of standard
      addition method on the accuracy for the determination under the selected
      analytical lines has been studied in detail. The results show that the linear
      correlations of standard curves were very good (R2 = 0.9988 to 0.9996) under the
      determined conditions. Detection limits of these trace impurities were in the
      range of 0.0134 to 0.0280 mg x L(-1). Sample recoveries were within 97.30% to
      107.50%, and relative standard deviations were lower than 5.86% for eleven
      repeated determinations. The detection limits and accuracies established by the
      experiment can meet the analytical requirements and the analytic procedure was
      used to determine trace impurities in sodium chromate by ion membrane
      electrolysis technique successfully. Due to sodium chromate can be changed into
      sodium dichromate and chromic acid by adding acids, the established method can be
      further used to monitor trace impurities in these compounds or other hexavalent
      chromium compounds.

PMID- 25970926
TI  - [Study on the method for the determination of trace boron, molybdenum, silver,
      tin and lead in geochemical samples by direct current arc full spectrum direct
      reading atomic emission spectroscopy (DC-Arc-AES)].
AB  - The method for the determmation of trace boron, molybdenum, silver, tin and lead
      in geochemical samples by direct current are full spectrum direct reading atomic
      emission spectroscopy (DC-Arc-AES) was established. Direct current are full
      spectrum direct reading atomic emission spectrometer with a large area of solid
      state detectors has functions of full spectrum direct reading and real-time
      background correction. The new electrodes and new buffer recipe were proposed in
      this paper, and have applied for national patent. Suitable analytical line pairs,
      back ground correcting points of elements and the internal standard method were
      selected, and Ge was used as internal standard. Multistage currents were selected
      in the research on current program, and each current set different holding time
      to ensure that each element has a good signal to noise ratio. Continuous rising
      current mode selected can effectively eliminate the splash of the sample. Argon
      as shielding gas can eliminate CN band generating and reduce spectral background,
      also plays a role in stabilizing the are, and argon flow 3.5 L x min(-1) was
      selected. Evaporation curve of each element was made, and it was concluded that
      the evaporation behavior of each element is consistent, and combined with the
      effects of different spectrographic times on the intensity and background, the
      spectrographic time of 35s was selected. In this paper, national standards
      substances were selected as a standard series, and the standard series includes
      different nature and different content of standard substances which meet the
      determination of trace boron, molybdenum, silver, tin and lead in geochemical
      samples. In the optimum experimental conditions, the detection limits for B, Mo,
      Ag, Sn and Pb are 1.1, 0.09, 0.01, 0.41, and 0.56 microg x g(-1) respectively,
      and the precisions (RSD, n=12) for B, Mo, Ag, Sn and Pb are 4.57%-7.63%, 5.14%
      7.75%, 5.48%-12.30%, 3.97%-10.46%, and 4.26%-9.21% respectively. The analytical
      accuracy was validated by national standards and the results are in agreement
      with certified values. The method is simple, rapid, is an advanced analytical
      method for the determination of trace amounts of geochemical samples' boron,
      molybdenum, silver, tin and lead, and has a certain practicality.

PMID- 25970927
TI  - [Application of Tessier-AAS to the non-biological transformation mechanism of
      chemical speciation of lead in red soil in agricultural area of central China].
AB  - The soil contamination of heavy metals, from the areas of mine, highway,
      industrial area, agricultural land and so on, is nowadays a serious issue all
      over the world. The contamination of heavy metals in large agricultural area
      might lead to the decrease of products quality and economic value. Actually, the
      accumulation amount of heavy metals by crops is much more related to the
      activated speciation, which is exchangeable and able to transform to the forms of
      carbonates, Fe-Mn oxides, organic matter and residual. Thus, the investigation to
      reveal the transformation mechanism of heavy metals caused by soil conditions
      might be appropriate to reduce the contaminated risk to crops. The vermicular red
      soil from the agricultural area of central China was used as sample in the paper,
      and the Tessier Sequential Extraction Procedure-atomic absorption spectroscopy
      (AAS) was applied to discuss the chemical speciation and non-biological
      transformation mechanism of Pb at different conditions. The results showed: the
      total amount of Pb is 32.56 mg x kg(-1), lower than the first level of the State
      Environmental Quality Standard for Soils. The Pb content of different speciation,
      with decreased concentration, is residual (54.55% of total Pb content), bound to
      Fe-Mn oxides, bound to organic matter, bound to carbonates and exchangeable. The
      pH value of red soil is related to the charge amount on surface of inorganic
      colloids and organic matter, and the water content of red soil would change the
      redox potential, effective for the variation of chemical speciation of Pb. The
      environmental factors of straw dosage and aging time could change Pb speciation,
      with Pb concentration of residual form the highest. The Muller index of Igeo is
      0.3025, indicating the contribution of human activities. The Tessier Sequential
      Extraction Procedure-AAS is effective for the non-biological transformation
      mechanism identification of Pb speciation in red soil.

PMID- 25970928
TI  - [Preparation of polyacrylonitrile/natural sand composite materials and analysis
      of adsorption properties of Pb(II) on it by FAAS].
AB  - Surfaces of natural sand particles were modified with (3-chloropropyl)
      trichlorosilane, so that bridging groups were introduced on the surfaces of
      natural sand particles; By grafting polyacrylonitrile onto the modified surfaces
      of the natural sand particles, a novelpolyacrylonitrile/natural sand composite
      material was prepared from the acrylonitrile, the azobisisobutyronitrile, the
      divinylbenzene and the modified natural sand particles, which are as functional
      monomer, initiator, either skeleton monomer or cross-linking agent and carrier
      respectively; the composite materials were characterized by using infrared
      spectroscopy and scanning electron microscopy; On the FTIR spectrum, the main
      characteristic peaks of various functional groups including nitrile, benzene
      ring, and silicon hydroxyl, which were from functional monomer, cross-linking
      agent and carrier respectively, were observed. On the SEM, two different cross
      section morphologies having different density which were from acrylonitrile and
      modified sand particles were observed; This proved that the polyacrylonitrile was
      decorated on modified sand particles during our preparation process. After
      preparing the composite materials, micro-column of separation and
      preconcentration was prepared using the composite materials as filler; the
      adsorption of some toxic heavy metal ions onto the composite materials was
      observed by flame atomic absorption spectrometry (FAAS); The results show that
      the adsorption of Pb2+ onto the composite materials was more stronger than the
      absorption of other toxic heavy metal ions, therefore, in this paper, the
      adsorption of Pb2+ onto the composite materials was mainly studied, at room
      temperature, when pH and flow rate of solution were 5. 4 and 4 mL x min(-1)
      respectively, the trace Pb(II) ions could be quantitatively adsorbed onto the
      composite materials; the maximum adsorption capacity of Pb(II) on the composite
      materials can reach 62.9 mg x g(-1). The column was eluted by 0.5 mol x L(-1) HCl
      and recovery of Pb(II) was more than 96%.

PMID- 25970929
TI  - [Analysis of XPS in the removal of Se(IV) from groundwater with pyrite].
AB  - Selenium (Se) is an elementary trace nutrient element for human but there is a
      very narrow range between deficit and toxic levels. Furthermore, excessive intake
      of Selenium is harmful for human. The product species of selenite which was
      removal by pyrite particles was studied in the present research In the
      experiments, the pyrite particles were prepared by the wet ball mill method, and
      surface analyses of pyrite before and after contact with Se(IV) were conducted
      using X-ray photoelectron spectroscopy (XPS). Besides, the prepared pyrite
      samples were also characterized using both X-ray diffraction (XRD) and scanning
      electron microscope (SEM). X-ray diffraction analysis indicated that the purity
      of the prepared pyrite particles was above 97%, and the characteristic
      diffraction peaks of the particles well matched with that of FeS2 crystalline.
      Scanning electron microscope determination showed the shape of the particles was
      approximate ball and the size was range from 80 to 180 nm. And thus the pyrite
      particles prepared by the wet ball mill method had less particle size, larger
      specific surface area and higher reactive ability. The batch experiments
      exhibited the pyrite particles were able to remove 95% of Se(IV) (20 mg x L(-1))
      from water within 12 hours. And the kinetic tests indicated reaction process
      between pyrite and Se(IV) fits a pseudo-first order kinetic model, which gives a
      pseudo-first order rate constant(kobs) of 0.26 h(-1). XPS analyses were using the
      XPSPEAK program which has a Gaussian Lorentzian function. The results clearly
      displays that Se(IV) prefer to react with the surface-bound S2(2-) rather than
      reacted with the surface-bound Fe2+ of pyrite particles. From XPS graph, it can
      be seen that the binding energy of sulfur element and iron element composed of
      pyrite shifted to the left a little, which means expensive state of sulfur
      element and iron element appeared on the pyrite surface. Analysis of the
      oxidation state of Se on the surface of pyrite particles by X-ray photoelectron
      spectra showed evidence for the reduction of Se(VI) to insoluble element Se(0)
      species. Besides, a spot of Se(IV) was existence on the surface of pyrite
      particles. The calculation results displayed that zero-valent selenium was
      dominarnt. At that, redox reaction was the main process when removal of Se(
      IVN)in aqueous environment with pyrite, along with sorption reaction at the same
      time. The results of removal of Se(IV) in groundwater using pyrite offer
      important theoretical value and practical significance.

PMID- 25970930
TI  - [The validation of the effect of correcting spectral background changes based on
      floating reference method by simulation].
AB  - There are some challenges in near-infrared non-invasive blood glucose
      measurement, such as the low signal to noise ratio of instrument, the unstable
      measurement conditions, the unpredictable and irregular changes of the measured
      object, and etc. Therefore, it is difficult to extract the information of blood
      glucose concentrations from the complicated signals accurately. Reference
      measurement method is usually considered to be used to eliminate the effect of
      background changes. But there is no reference substance which changes
      synchronously with the anylate. After many years of research, our research group
      has proposed the floating reference method, which is succeeded in eliminating the
      spectral effects induced by the instrument drifts and the measured object's
      background variations. But our studies indicate that the reference-point will
      changes following the changing of measurement location and wavelength. Therefore,
      the effects of floating reference method should be verified comprehensively. In
      this paper, keeping things simple, the Monte Carlo simulation employing
      Intralipid solution with the concentrations of 5% and 10% is performed to verify
      the effect of floating reference method used into eliminating the consequences of
      the light source drift. And the light source drift is introduced through varying
      the incident photon number. The effectiveness of the floating reference method
      with corresponding reference-points at different wavelengths in eliminating the
      variations of the light source drift is estimated. The comparison of the
      prediction abilities of the calibration models with and without using this method
      shows that the RMSEPs of the method are decreased by about 98.57%
      (5%Intralipid)and 99.36% (10% Intralipid)for different Intralipid. The results
      indicate that the floating reference method has obvious effect in eliminating the
      background changes.

PMID- 25970931
TI  - [A simple design of functional near-infrared spectroscopy system].
AB  - With the development in last twenty years, functional near-infrared spectroscopy
      (fNIRS) is a non-invasive brain imaging technique which widely used in cognitive
      neuroscience studies. Based on mechanism of neurovascular coupling, increased
      functional neural activities in brain induce higher regional cerebral blood flow,
      which will cause relative concentration change of oxygenated and deoxygenated
      hemoglobin. In this paper, a single channel continuous wave fNIRS system based on
      multi-function data acquisition board was proposed. With the benefits of narrow
      spectral peaks and low divergence, laser diodes provided a better accuracy for
      measurement with optimal dual-wavelength of 690 and 830 nm. Frequency
      multiplexing technique was used to distinguish light sources from different
      emitters, and remove environmental stable interference sources such as ambient
      light and line power noise as well. LabVIEW was used to design graphical user
      interface with functionalities including source sequence schedule, auto gain
      setting, digital inhase and quadrature demodulation, data visualization and
      storage. The experimental results during holding breath and mental arithmetic
      task indicated that our system was capable of monitoring regional concentration
      change of hemoglobin in real time, and detecting activation associated with
      advanced brain functions.

PMID- 25970932
TI  - [The linear hyperspectral camera rotating scan imaging geometric correction based
      on the precise spectral sampling].
AB  - As the rotation speed of ground based hyperspectral imaging system is too fast in
      the image collection process, which exceeds the speed limitation, there is data
      missed in the rectified image, it shows as the_black lines. At the same time,
      there is serious distortion in the collected raw images, which effects the
      feature information classification and identification. To solve these problems,
      in this paper, we introduce the each component of the ground based hyperspectral
      imaging system at first, and give the general process of data collection. The
      rotation speed is controlled in data collection process, according to the image
      cover area of each frame and the image collection speed of the ground based
      hyperspectral imaging system, And then the spatial orientation model is deduced
      in detail combining with the star scanning angle, stop scanning angle and the
      minimum distance between the sensor and the scanned object etc. The oriented
      image is divided into grids and resampled with new spectral. The general flow of
      distortion image corrected is presented in this paper. Since the image spatial
      resolution is different between the adjacent frames, and in order to keep the
      highest image resolution of corrected image, the minimum ground sampling distance
      is employed as the grid unit to divide the geo-referenced image. Taking the
      spectral distortion into account caused by direct sampling method when the new
      uniform grids and the old uneven grids are superimposed to take the pixel value,
      the precise spectral sampling method based on the position distribution is
      proposed. The distortion image collected in Lao Si Cheng ruin which is in the
      Zhang Jiajie town Hunan province is corrected through the algorithm proposed on
      above. The features keep the original geometric characteristics. It verifies the
      validity of the algorithm. And we extract the spectral of different features to
      compute the correlation coefficient. The results show that the improved spectral
      sampling method is better than the direct sampling method. It provides the
      reference for the similar product used on the ground.

PMID- 25970933
TI  - [A high sensitivity micro-ring humidity sensor based on U-shaped waveguide
      coupled single micro-ring structure].
AB  - The paper proposes a novel high sensitivity humidity sensor based on a U-shaped
      waveguide-coupled single micro-ring, Polyimide is used as the wet material, the
      refractive index of humidity-sensing part changes as relative humidity changes,
      thus leading to a obvious peak drift. The transfer function of the structure is
      derived basing on transfer matrix method and the paper mainly discusses the
      influence on the output spectrum with different humidity-sensing parts. Through
      the theoretical simulation of Matlab, the whole structure of U-shaped waveguide
      coupled single micro-ring is proved to be the best humidity-sensing part. The
      free spectral range (FSR) will be doubled compared to the traditional single
      micro ring structure while the length between the two coupling points of the U
      shaped waveguide is an integer multiple of circumference of the micro-ring. When
      the relative humidity of external environment changes from 10% RH to 100% RH, the
      output spectrum appears a obvious drift from 0.027 to 0.191 microm and the
      sensitivity reaches up to 0.0018 microm/% RH. Compared to FBG humidity sensor
      with high sensitivity, the sensitivity in this article is increased by 10 to 100
      times, achieving a high sensitivity in the sense of humidity when the wide range
      of filter frequency selection is taken into account.

PMID- 25970934
TI  - [Design and analysis of a novel light visible spectrum imaging spectrograph
      optical system].
AB  - A novel visible spectrum imaging spectrograph optical system was proposed based
      on the negative dispersion, the arbitrary phase modulation characteristics of
      diffractive optical element and the aberration correction characteristics of
      freeform optical element. The double agglutination lens was substituted by a
      hybrid refractive/diffractive lens based on the negative dispersion of
      diffractive optical element. Two freeform optical elements were used in order to
      correct some aberration based on the aberration correction characteristics of
      freeform optical element. An example and frondose design process were presented.
      When the design parameters were uniform, compared with the traditional system,
      the novel visible spectrum imaging spectrograph optical system's weight was
      reduced by 22.9%, the total length was reduced by 26.6%, the maximal diameter was
      reduced by 30.6%, and the modulation transfer function (MTF) in 1.0 field-of-view
      was improved by 0.35 with field-of-view improved maximally. The maximal
      distortion was reduced by 1.6%, the maximal longitudinal aberration was reduced
      by 56.4%, and the lateral color aberration was reduced by 59. 3%. From these
      data, we know that the performance of the novel system was advanced quickly and
      it could be used to put forward a new idea for modern visible spectrum imaging
      spectrograph optical system design.

PMID- 25970935
TI  - Theragnostics--a silent revolution.

PMID- 25970936
TI  - Current concepts in minimal hepatic encephalopathy.
AB  - Minimal hepatic encephalopathy (MHE) defines the presence of neurocognitive
      impairments in patients with cirrhosis or portal-systemic shunting that show a
      normal neurologic and psychiatric status on clinical examination. Although
      ammonia has the central role in MHE pathogenesis, factors such as infection,
      oxidative stress, manganese or intestinal bacterial overgrowth contribute to the
      development of the neurocognitive deficits associated with this disease. Many
      methods have proven useful in identifying MHE but because of the major drawbacks
      (standardization requirements, high price, sophisticated equipment, and limited
      access) a gold-standard test is still missing. Although beneficial, the treatment
      of MHE is not routinely recommended and should be taken into consideration in
      patients at risk for accidents and in those with cognitive complaints or decline
      in work performance.

PMID- 25970937
TI  - Electrocardiographic changes in the most frequent endocrine disorders associated
      with cardiovascular diseases. Review of the literature.
AB  - Car- diovascular abnormalities associated with endocrine diseases are often
      frequent and due to complex relationships between endocrine glands (with internal
      secretion) and cardiovascular system (heart and vessels). Certain hormones
      secreted by the endocrine glands (particularly the thyroid and pituitary gland)
      excesses or deficiencies, are involved in morphogenesis, growth processes and
      activity regulation of cardiovascular system, most often in connection with the
      autonomic nervous system. There are also a lot of electrocardiographic changes
      caused by hormonal disorders that requires differential diagnosis and represents
      the source of erroneous diagnosis. Endocrine pathology occurred later than a
      heart disease, may worse heart function. Ignoring the cardiovascular events that
      may occur in the evolution of endo- crine diseases, may induce increased
      mortality due to cardiovascular complications.

PMID- 25970938
TI  - Aspects of physician-patient communication in the program of smoking cessation.
AB  - The doctor-smoker patient communication is essential for smokers to realize the
      harmful effects of tobacco on health and the benefits of smoking cessation.
      Nicotine found in cigarettes is a powerful drug and a direct dependency
      generator, which makes smoking cessation difficult, the withdrawal syndrome being
      hard to overcome for many smokers. The doctor-smoker patient communication is a
      complex process of data, information and knowledge transmission, subjected to
      some semiotic rules. In the Counseling Center for Smoking Cessation (CCSC) from
      the Rehabilitation Clinical Hospital of Iasi the medical and psychological
      counseling and the pharmacologic therapy for smoking cessation is ensured by the
      qualified personnel. CCSC was founded in 2005, when the hospital was included in
      European Program: "European Network Smoke-Free Hospital", and experienced an
      important development in 2007 with the initiation "Stop Smoking" National Program
      of Ministry of Health. The doctor-smoker patient communication in the CCSC was
      conducted during the smoker's recruitment, therapeutic and post therapeutic
      period, a special place being occupied by the doctor-medical staff communication,
      including smoker medical students. The number of people who became nonsmokers
      after being counseled at our center was the evidence of the effectiveness of this
      communication. The obtained results determined us to join the global fight
      against smoking and to propose the introduction of the smoking cessation program
      in the curriculum of the medical education institutions.

PMID- 25970939
TI  - Implementing EBUS TBNA: first experience and review of literature.
AB  - Lung cancer has a very dismal prognosis and careful diagnosis and staging is of
      outmost importance. EBUS has become a cornerstone investigation for diagnosis and
      staging and current guidelines stress that there is a steep learning curve when
      introducing this tech- nique in practice (only 30 procedures are considered
      necessary). Over a period of 10 months a total of 21 patients have been addressed
      to our unit for an EBUS TBNA procedure. Only three were referred for staging
      purposes (for lung, digestive and cervix cancers) the others being primary
      diagnostic approaches where simpler procedures had previously failed. Procedures
      were initially performed under local anesthesia (3 cases) then under general
      anesthesia and jet ventilation using a laryngeal mask approach. Mediastinal lymph
      node group 7 was the most frequent target (9 cases) followed by group 4R (8
      cases) and peribronchial tumoral processes (7 cases); one case did not required
      any needle-aspiration. On average each examination resulted in the sampling of
      1.4 targets. There were no significant procedure related severe adverse events.
      Although 21 G cytology needles were used, adequate histological samples were
      obtained for 11 cases and cytology was the examination of choice for 9 cases. The
      pathology/cytology results were retrospectively assessed as satisfactory for 15
      cases (confirmed neoplastic or other disease) and inconclusive for 5 cases. Non
      neoplastic disorders were represented by sarcoidosis, tuberculosis and
      bronchogenic cyst (3 cases). The procedure can be considered fast and safe;
      trained pathology personnel play an extremely important role: presently referrals
      are rare for staging purposes.

PMID- 25970940
TI  - Adverse reactions of biological therapy for psoriasis.
AB  - AIM: To detect in patients with psoriasis the adverse effects during TNF-a
      inhibitor therapy. MATERIAL AND METHODS: Fifty-seven patients with psoriasis,
      aged between 12 and 75 years were analyzed. They were treated with different TNF
      alpha antagonists, the maximum treatment duration being 59 months. All patients
      were followed monthly after the initiation of therapy by clinical checkup, then
      every 3 months during the first 6 months of treatment by laboratory screening,
      and then every 6 month. Chest x-ray and tuberculin intradermal skin test were
      performed annually or as needed. All symptoms reported by patients were recorded,
      the treating doctor deciding the need for additional investigations or specialist
      consult. RESULTS: Of the total of 57 patients with psoriasis on biological
      therapy, 9 patients developed diseases requiring temporary or permanent
      discontinuation of therapy. The recorded adverse reactions were: infectious
      (pulmonary tuberculosis, pulmonary empyema), oncologic (rectal cancer, renal
      cancer), dermatologic (vesiculobullous erythema multiforme major, nodular
      hypodermtis, secondary erythroderma, and hives) disorders. CONCLUSIONS: Despite
      its adverse reactions, biological therapy is safe and is a necessary tool in the
      treatment of moderate and severe forms of psoriasis unresponsive to other
      treatments.

PMID- 25970941
TI  - Thyroid fine-needle biopsy: aspiration versus capillary.
AB  - Thyroid nodules are a common pathology of the thyroid gland. Thyroid fine-needle
      biopsy (FNB) is a technique used as the first step in the assessment of thyroid
      nodules. Some au- thors have demonstrated the superiority of nonaspiration
      compared with aspiration biopsy. AIM: The objective was to assess whether there
      are significant differences between the two thyroid biopsy techniques. MATERIAL
      AND METHODS: The study group comprised 309 patients with thyroid nodules admitted
      to the Endocrinology Clinic of the Iasi "St. Spiridon "Hospital between 2005 and
      2008 in which fine-needle nonaspiration or aspiration biopsy was performed. The
      slides were read by one pathologist. The smears were stained using the May
      Grunwald-Giemsa method (MGG). The quality of smears obtained by the two sampling
      techniques was evaluated by using the scoring system developed by Mair. RESULTS
      AND DISCUSSION: No differences in smear quality between the two sampling
      techniques in terms of blood contamination, amount of cellular material, degree
      of cellular degeneration, degree of cellular trauma, and preservation of
      appropriate architecture were found. CONCLUSION: The results of this study show
      that the sensitivity and specificity of both techniques allow their use as
      standard screening methods for thyroid nodular lesions.

PMID- 25970942
TI  - Chronic occupational stress exposure may increase the vulnerability to acoustic
      trauma in military professionals.
AB  - Today little is known about the connection between chronic stress exposure and
      hearing loss. These effects cannot be explained by differences in HPA axis
      response but recent studies saying that chronic stress induced limbic system
      alterations spread to nonlimbic areas affecting auditory system might be the key.
      On the other hand we know that subjects exposed to chronic stress may prove
      hypersensitivity to novel stressors. The aim of this study is to confirm that
      occupational chronic stress (OCS) exposure determines vulnerability to acoustic
      trauma and to establish a method to identify individuals at risk prior to their
      exposure to high intensity acoustic stimulus. MATERIAL AND METHODS: 60 military
      personnel with known acoustic trauma injury evidentiated through audiograms and
      occupational chronic stress exposure quantified through validated questionnaires
      were exposed to mild novel stressor: occupational medicine evaluation and
      clinically assessed for maladaptive cardiovascular response (MCVR). Employees
      were split in two groups, group 1 (MCVR) and group 2 (non MCVR). RESULTS: We
      found positive correlation between level of perceived OCS and level of hearing
      loss on entire group and between groups with values of parameters significantly
      higher in group 1. Subjects exposed to OCS with hypersensitivity to novel
      stressor evidentiated through maladaptive cardiovascular stress response may be
      more vulnerable to high intensity acoustic stimulus and consequently acoustic
      trauma. CONCLUSIONS: Establishing methods and biomarkers that help us indentify
      individuals at risk of developing acoustic trauma might decrease the high burden
      of hearing loss.

PMID- 25970943
TI  - Erythema multiforme--etiopathogenic, clinical and therapeutic aspects.
AB  - AIM: To present the epidemiological, etiopathogenic, clinical and therapeutic
      aspects in Erythema multiforme (EM). MATERIAL AND METHODS: This is a 3-year
      retrospective study based on medical records of patients with EM admitted to the
      Dermatology Clinic. Forty patients were included in this study. The obtained data
      allowed the classification of patients according to their distribution by sex,
      age group, area of residence, etiology, clinical aspects, and type of
      administered treatment. RESULTS: The prevalence of EM during the 3 study years
      was 0.4%. EM prevailed among the rural population, more frequently in women. The
      minimum age at which EM was diagnosed was 12 years and maximum age 78 years, with
      a peak incidence between 20-40 years old (37.5% cases). In 42.50% of the cases EM
      was drug-induced, and in 17.50% of cases it was caused by infection with herpes
      simplex virus (HSV). There were 18 cases of erythemotous-papular EM (45%), 14
      cases of erythematous--vesiculobullous EM (35%) and 8 cases of recurrent EM
      (20%). All patients received treatment with antihistamines and nonspecific
      desensitizing agents. Systemic corticotherapy was used in 22 cases. Three
      patients received treatment with acyclovir. CONCLUSIONS: Erythema multiforme is a
      rare skin condition, easily diagnosed based on its characteristic clinical
      appearance, but remains a challenge for the physician in terms of establishing
      its causal agent.

PMID- 25970944
TI  - Clinical and epidemiological aspects of gout, a dysmetabolic disabling disorder.
AB  - Gout is a disease caused by disturbances of uric acid metabolism and it manifests
      as rheumatic pain with various clinical and developmental issues, but without any
      major diagnosis problems; it might unfavorably interfere with other metabolisms,
      especially with carbohydrate and lipid metabolism that interact and erode each
      other. AIMS: To provide clinical and laboratory data and to follow the
      development of gout in patients treated in the clinic. MATERIAL AND METHODS: The
      study included 28 patients (25 male and 3 female patients) diagnosed with gout,
      admitted to the First Clinic of Rheumatology of the Clinical Rehabilitation
      Hospital Iasi during 2012-2013. RESULTS AND DISCUSSION: A new diagnostic method,
      dual energy computed tomography, was effective in some selected cases of gout, as
      it may reveal uric acid crystals with specific densities in the damaged joints
      and periarticular soft tissues. CONCLUSIONS: Gout is a disorder that occurs when
      the uric acid produced by the body is stored in the form of crystals in joints
      and/or soft tissues. In joints, uric acid crystals precipitate and cause
      inflammatory arthritis that leads to swelling, redness, heat, pain and joint
      functional impotence.

PMID- 25970945
TI  - Diagnostic and prognostic value of presepsin in the emergency department.
AB  - Sepsis syndrome is a common situation and has devastating implications on health
      care systems worldwide. Biomarkers may have an important role to highlight the
      presence, absence or severity of sepsis. MATERIAL AND METHODS: Retrospective
      study is conducted on a group of 95 suspected sepsis patient (0.16%) out of a
      total of 56,996 patients that were presented in the Emergency
      Department/Emergency County Hospital "St. Spiridon" from Iasi during 01.01.2012
      01.12.2012. The study aims to establish the following: the incidence of sepsis
      diagnosis, analysis of prognostic factors, relationship between the presepsin
      value and clinical outcome. RESULTS: In men, there was a distribution of cases
      between the age of 22 years up to 89 years with an average confidence interval
      between 59.32 and 67.23 years, and the distribution of cases varies among women
      from age of 40 years up to 93 years, with an average confidence interval between
      65.53 and 75.47 years The most frequent primary source of infection is localized
      at the pulmonary level, in a total of 21.1%, followed by abdominal location
      occurring in a total 14.7%. Area under the curve in ROC curve analysis regarding
      mortality showed significant values of area for presepsin (0.859), leukocytes
      (0.790), traumatic injuries association (0.761) and the presence of
      gastrointestinal history. CONCLUSIONS: Presepsin has diagnostic value, early
      prognostic value and is an early marker of mortality in septic patients. Trauma
      associated with severe systemic infection leads to an increase in mortality.

PMID- 25970946
TI  - Smoking cessation, pulmonary rehabilitation and quality of life at smokers with
      COPD.
AB  - Aim was to compare the quality of life (QoL) at the smokers with COPD who quit
      smoking and have completed a pulmonary rehabilitation program with those who
      received usual treatment. MATERIAL AND METHODS: 437 smokers with COPD stages II
      and III were counseled and treated to smoking cessation and completed COPD
      Assessment Test (CAT) at the beginning and at the end of 12 weeks of treatment.
      113 patients were enrolled in a 12 weeks supervised pulmonary rehabilitation
      program (PR group) and 324 smokers received usual treatment for COPD and were
      monitored for 12 weeks (non-PR group). The initial HbCO > 2%, and every patient
      completed an initial CAT. RESULTS: Initially, CAT scores varied between 26 and
      38. At the end of the period, CAT scores in the PR group were between 7 and 16
      and in the non-PR group CAT scores were between 20 and 26, and additionally the
      smoking cessation failure at an important number of non-PR members (45.98%) (in
      PR group, 16.81%). There were reported as well higher rates of long-term
      abstinence in the adherent patients to PR than the other group. CONCLUSIONS: COPD
      smokers who completed the PR presented important QoL improvements, better CAT
      score than COPD smokers usually treated. A better PR adherence seems to be
      related with higher rates of sustained long term abstinence.

PMID- 25970947
TI  - Incidence and risk factors of Clostridium difficile infection in patients with
      inflammatory bowel disease.
AB  - Recent changes in the epidemiology of Clostridium difficile infection (CDI)
      include the identification of patients with inflammatory bowel disease (IBD) as a
      group at risk in comparison to the general population. AIM: To identify the
      incidence and risk factors for CDI among patients with IBD. MATERIAL AND METHODS:
      Case-control study of 78 patients diagnosed with IBD, hospitalized at the Iasi
      Institute of Gastroenterology and Hepatology between January 2012 and -July 2014.
      Demographic data and clinical characteristics were reviewed for all patients. IBD
      patients with positive C. difficile toxins A and B tests were matched by sex, age
      and type of IBD with IBD patients hospitalized in the same period with negative
      C. difficile toxins tests. RESULTS: Both groups were comparable for baseline
      characteristics. Of the 78 patients diagnosed with IBD included in the study, C.
      difficile was detected in 26 patients (33.33%). There was no statistical
      difference regarding length of hospital stay (10.42 +/- 7.34 vs. 8.01 +/- 16.14
      days, p = 0.129) between the two study groups. Risk factors for CDI in patients
      with IBD were: ulcerative colitis (OR = 1.90, CI = 1.320-2.720, p = 0.001), use
      of proton pump inhibitors (OR = 1.57, CI = 1.133-2.032, p = 0.012), previous
      antibiotic use (OR = 2.3, CI = 1.587-3.332, p < 0.0001), and albumin < 3 g/dl (OR
      = 1.78, CI = 1.023-5.558, p = 0.038). Immunosuppressive and anti TNF-alpha
      treatment were not risk factors for C. difficile development in patients with
      IBD. CONCLUSIONS: CDI in patients with IBD is a serious infection and should be
      treated aggressively with close clinical follow-up. Ulcerative colitis, previous
      treatment with antibiotics and proton pump inhibitors represent risk factors for
      CDI development in patients with IBD.

PMID- 25970948
TI  - Coexistence of celiac disease and systemic lupus erythematosus in a 6-year-old
      girl-case report.
AB  - Systemic lupus erythematosus (SLE) is a serious and potentially fatal syndrome
      characterized by an autoimmune assault on various organs and systems that may
      include the skin, joints, central nervous system, heart and kidneys. Recent
      research shows that gluten sensitivity causes more than just celiac disease and
      gluten has been linked to numerous autoimmune conditions. We report here a 6-year
      old girl presenting with malaise, abdominal pain, loss of appetite, abdominal
      distension. After three weeks she developed other symptoms such as arthralgias,
      malar rash, being finally diagnosed with SLE and possible autoimmune hepatitis.
      The suspicion of celiac disease was based on a combination of symptoms (poor
      growth, iron deficiency anemia, chronic abdominal pain, abdominal distension,
      constipation, "sad child"), IgA deficiency, in the presence of SLE diagnosis.
      Positive diagnosis of celiac disease was confirmed by the presence of an anti IgG
      anti-transglutaminase antibodies titer of 120 EU/ml (normally less than 20
      EU/ml). Small bowel biopsy showed a IIIB1 stage according to the Marsh
      classification. Three methylprednisolone pulses were promptly administered,
      followed by oral prednisone (2 mg/kg bw/day) with a good outcome.

PMID- 25970949
TI  - Diabetes mellitus, chronic complication in patients with acromegaly: case report
      and review of the literature.
AB  - Disturbances of glucose metabolism are frequently observed in patients with
      acromegaly. Excess amounts of GH and IGF1 interacts with metabolic regulation,
      and indeed, GH hypersecretion is associated with hepatic and peripheral insulin
      resistance; this and also other mechanisms are involved in the development of
      diabetes mellitus. It can quickly improve if the levels of GH decline after the
      therapy. CASE REPORT: We present a patientof 54 years old, admitted in the clinic
      in 2009, with diagnosis of acromegaly. MRI scan reveals an expansive pituitary
      tumor 15/16/17 mm. Values of GH, IGF1 and blood glucose were much above normal.
      Body mass index 27, 5 kg/m2. After 12 months of a medical treatment with
      somatostatin analogues, the evolution of blood parameters was favorable, but the
      patient has discontinued his treatment. At the hospitalization in 2012 there is a
      precarious control of the diabetes under oral antidiabetic agents. A new
      treatment has been applied: it was practiced surgical transsphenoidal ablation.
      At last admit, May 2014, the value IGF1 has been normal, GH has been below 1
      ng/mL, and HbAlc was 5.27%. Dyslipidemic syndrome has been constantly present;
      the values of triglycerides and cholesterol should be a little more upper limit.
      CONCLUSIONS: Following successful treatment of acromegaly with surgery, glucose
      tolerance improves. Balancing type 2 diabetes, with return to normal HbA1c and
      the decrease in cholesterol and triglycerides values, represents the result of
      favorable normalization GH in our patients with acromegaly.

PMID- 25970950
TI  - Lymphoma in an HIV-positive patient.
AB  - HIV/AIDS is considered to be revealing of oncological diseases, of which most
      frequent are lymphomas. The main causes for this type of disease are non
      adherence and non-compliance to antiretroviral therapy (ART). We are hereby
      presenting a clinical case of lymphoma in an HIV-infected adult, with non
      adherence for 30 months. In such a case the interdisciplinary collaboration with
      the hematologist was essential for the patient's survival.

PMID- 25970951
TI  - ST segment depression in asymptomatic male patient with normal coronary arteries.
AB  - ST segment depression and T waves inversion are electrocardiographic (ECG)
      repolarization abnormalities often encountered in clinical medical practice that
      have been proved to predict future cardiovascular events. We present the case of
      a 62-year-old male patient, asymptomatic, with ST segment depression and inverted
      T waves discovered incidentally on resting ECG. Echocardiographic and laboratory
      examinations ruled out multiple causes of ECG abnormalities. Suspecting a silent
      myocardial ischemia, an ECG exercise stress test was performed; it revealed
      pseudo normalization of T waves during exercise and early recovery phase. Being
      inconclusive, a coronary CT was the final election test; it showed normal
      coronary arteries with no stenosis, the patient being scheduled for regular
      follow-up. The possible causes of ST segment depression are reviewed since it is
      important that early cardiovascular signs especially in asymptomatic patients to
      be prevented and detected.

PMID- 25970952
TI  - Pyoderma vegetans developed on chronic leg ulcer.
AB  - Pyoderma vegetans is a rare disorder that more commonly affects middle-aged
      persons, with a male predilection. It is characterized by vegetating lesions that
      coalescence into a plaque with eroded surface, covered by purulent discharge and
      crusts. The etiology of this disease is not known with certainty, but it is often
      associated with bacterial infections in immunocompromised patients. We report the
      case of a 73-year-old men who presented to the Iasi Dermatology Clinic with a
      large, irregular, relatively well-defined dermohypodermic ulcer, with infiltrated
      sclerosing borders, accompanied by pain, with the floor covered in the Northern
      part by a proliferative, vegetative bleeding area, and the rest by a yellowish
      secretion and cellular debris, located on the left leg. Bacteriological
      examination of ulcer secretion identified Pseudomonas aeruginosa.
      Anatomopathological examination confirmed the development of Pyoderma vegetans on
      chronic leg ulcer. Under specific treatment for chronic leg ulcer and eradication
      of infectious focus the outcome was favorable both in terms of trophic ulcer scar
      ring and Pyoderma vegetans healing.

PMID- 25970953
TI  - Epidemiological evaluation of the outcomes after video-assisted thoracoscopic
      talcage in neoplastic pleurisy.
AB  - AIM: Clinical-epidemiological investigations for further assessing the importance
      of video-assisted thoracoscopy in the treatment y of patients with neoplastic
      pleurisy. MATERIALS AND METHODS: The researches included a group of 72 patients
      (31.9% men and 68.1% women aged 31-81 years, mean age +/- 60 years) with
      neoplastic pleurisy who underwent pleural symphysis by video-assisted
      thoracoscopic talcage. For statistical-mathematical processing and interpretation
      the Pearson correlation index with the level of significance at p = 0.05 and
      highly significant at p < 0.005 was used. RESULTS: Neoplastic pleurisy
      prevalently affected the age groups 51-80 years (84.9%). Dyspnea was present in
      all cases, and patient history at the time of admission revealed 14 conditions,
      of which 25% were lung cancers. Macroscopically nodular and vegetative tumors
      were found in 66.7% of cases. An amount of 1000-2000 ml of pleural fluid was
      found in 44.5% of the cases and a serocitrin appearance in 50%. In 23.6% of the
      cases cytology results were positive for malignancy and in 13.8% suspicious. In
      65.2% of the cases the pleural fluid was exudative and anatomopathology was
      suggestive of adenocarcinoma in 34.7% of the cases and breast cancer in 18%. The
      prevalence of recurrences varied from 1 month to more than 7 months, with 36.4%
      for 1-2 months. CONCLUSIONS: The obtained additional data support the important
      role of pleural symphysis by video-assisted thoracoscopic talcage in the patients
      with neoplastic pleurisy.

PMID- 25970954
TI  - Retromolar trigone--oropharynx junction maligns tumor surgery: transmandibular
      versus oral approach.
AB  - AIM: This study proposes a new approach to a borderline pathology between
      Otorhinolaryngology (E.N.T.) and Oral and Maxillofacial Surgery (O.M.F.), the
      malignant tumors of the oropharyngeal and retromolar trigone junction. MATERIAL
      AND METHODS: 52 cases of retromolar trigone and oropharynx malign tumors were
      solved in the ENT department of "St. Spiridon" Universitary Hospital Iasi between
      2012 and 2014. All patients were males, 35-64 years old, in different TNM stages.
      The novelty stands in the multidisciplinary approach, with an operating team
      consisting of both E.N.T. and O.M.F. surgeons, which joined their knowledge and
      expertise in order to offer a better treatment for the patient. Human Papilloma
      Virus (HPV) infection has been known as a trigger factor in head and neck
      cancers. The connection between HPV infection and malignant tumors of the
      oropharyngeal--retromolar trigone junction, together with the other traditional
      risk factors (smoking, alcohol, stress and sexual behavior) are involved in the
      therapeutic protocols, improving the life quality, the survival rate and reducing
      the treatment costs. RESULTS AND DISCUSSION: Excision of the malignant tumors at
      the level of the junction between the oropharynx and retromolar trigone often
      requires repairing the tissular defects that remain using different flaps.
      Postsurgical mecanotherapy (physiotherapy) under the surveillance of an
      experienced physiotherapist is also needed for a complete recovery. CONCLUSIONS:
      This therapeutical protocol aims to assure a better life quality for the
      patients, with a faster postsurgical recovery and social reinsertion by reducing
      the healing time of the areas affected by inflammation and necrosis generated by
      the neoplastic process.

PMID- 25970955
TI  - Pregnancy and recurrence rates in infertile patients operated for ovarian
      endometriosis.
AB  - AIM: The study deals with the preoperative ultrasound diagnosis of ovarian
      endometriosis, postoperative ultrasound reassessment, laparoscopic surgical
      resolution of ovarian endometriosis, estimation of recurrence risk 12 months
      after surgery by ultrasound, reappearance of clinical symptoms (such as pain) or
      second-look laparoscopy, and pregnancy rate 2 years after surgery. MATERIAL AND
      METHODS: 140 patients with en- dometriosis and infertility admitted to the Iasi
      "Cuza-Voda" Clinical Hospital of Obstetrics and Gynecology between the years 2009
      2011 were included in the study. The patients were divided into 2 groups: group 1
      59 cases that refused in vitro fertilization procedures, did not afford in vitro
      fertilization (IVF) or had minimal endometriosis and young ages and thus a
      possibility of delaying treatment, and group 2--62 cases which underwent IVF
      procedures immediately after surgery. RESULTS: No significant differences in the
      chance of becoming pregnant were found between the two groups (chi2 = 2.06, p =
      0.0891, 95% CI); in group 1, 11.86% pregnancies were obtained while in group 2
      the pregnancy rate was 11.29%. Based on the nonparametric method of analysis of
      contingency tables we could estimate the odds of becoming pregnant in the study
      groups, obtaining an odds ratio (OR = 1.16, CI: 1.04-2.23, 95% CI). This result
      indicated that in group 1 the odds of becoming pregnant was not significantly
      higher, and the estimation was made for a confidence interval of 95%. The study
      had in view the assessment of pregnancies obtained in the study groups and the
      time interval (number of weeks) from the time of intervention until the
      occurrence of pregnancy. The Kaplan-Meier analysis enabled the assessment of the
      mean value and the median value of the number of weeks until becoming pregnant,
      and these values did not show significant differences (chi2 = 1.55, p = 0.212,
      95% CI). CONCLUSIONS: For endometriosis associated with infertility, hormonal
      suppression does not improve fertility, and therefore surgery followed by
      controlled ovarian hyperstimulation and intrauterine insemi- nation (IUI),
      provided the anatomy of the pelvis is preserved in early cases or in vitro
      fertilization in severe cases is preferred.

PMID- 25970956
TI  - Benign breast disease and the risk of breast cancer in the next 15 years.
AB  - AIM: Fibrocystic mastosis (FCM) is defined by the totality of dystrophic changes
      of the mammary tissue, the grouping in the form of fibrosis of epithelial,
      cystic, metaplastic and hyperplastic alterations. A very good estimation of the
      cancer risk is related specifically to the microscopic aspect. Other factors, the
      family history as well as the presence of an inherited gene determining the
      increase in the risk of breast cancer are also considered. But, if a woman known
      with fibrocystic mastosis has not undergone any biopsy, then it is impossible to
      calculate the specific individual risk of developing cancer. MATERIAL AND
      METHODS: The data collected as a study material and considered refer to: the
      total num- ber of cases investigated and diagnosed with fibrocystic mastosis, the
      annual distribution of this disease cases, the distribution of the cases
      according to age groups, admission reasons, clinical examination, personal
      pathologic history clinically significant for the basic disease (the main
      diagnosis), the family medical history significant for the basic disease, the
      anatomopathological diagnosis. RESULTS: Between 2004 and 2006, at "Cuza Voda"
      Obstetrics and Gynecology Hospital of Iasi, a maximum number of cases is noticed
      in 2006, when there were 147 cases, and the lowest number of cases was in 2005.
      There was high frequency of the anatomopathological examinations that highlighted
      the presence of fibrocystic lesions (both proliferative and non-proliferative),
      and the second most often diagnosis is fibroadenoma. Though fibrocystic mastosis
      is not clearly defined, it is still admitted that in order to support this
      diagnosis it is first compulsory to exclude malignant tumours. CONCLUSIONS: Only
      in 5% of the women with fibrocystic mastosis cellular changes can be revealed in
      the form of atypical hyperplasia, which are a risk factor for cancer. The lesion
      that delimits cancer from non-cancer is ductal carcinoma in situ. An incidence of
      over 20% is present in the countries that use mammographic screening programmes,
      mammographic surveillance programmes and programmes for the guided localization
      of nonpalpable lesions of the mammary gland.

PMID- 25970957
TI  - Intussusception in infants--storm from a clear sky.
AB  - Intussusception is one of the most common causes of acute abdominal conditions
      requiring surgical therapy in infants and babies. Due to the breakthroughs of
      pediatric intensive care and imaging methods, which may sometimes replace
      therapeutic methods, this condition, which used to be associated with high
      morbidity and mortality rates, is now more easily detected and treated
      immediately, even by non-surgical means. Nevertheless, there still is a high
      percent of cases in whom the diagnosis is set relatively late and who require
      laborious surgical procedures and extensive intestinal resections. These cases
      have high morbidity rates, the condition sometimes has a negative course and the
      patients die. We conducted an analytical retrospective study on a group of 49
      patients diagnosed with intussusceptions, hospitalized and treated in the
      Pediatric Surgery Ward of the Children's Hospital of Iasi City during 5 years.
      Although the demographics and clinical presentation of our patients is largely in
      agreement with literature data, we note that 69.4% of the patients came to the
      hospital 24 hours after the onset of their symptoms, which delayed diagnosis
      setting, ruled out non-surgical therapy and thus led to a high rate of
      postoperative complications (24.5%) and also to a high mortality rate (6.6%).

PMID- 25970958
TI  - Urogenital prolapse--current methods of surgical treatment.
AB  - Several combined surgical procedures have been described, but connective tissue
      deficiency required the use of some "prostheses" instead of conventional methods
      based exclusively on correction by suture. AIM: Assessment of the techniques used
      for the repair of stress urinary incontinence (SUI) and anterior vaginal wall
      prolapse, as well as the incidence of intraoperative and postoperative incidents
      and complications. MATERIAL AND METHOD: The study was conducted between January
      2007 and December 2011 at the 1st Clinic of Obstetrics and Gynecology Iasi. The
      diagnosis was made on clinical criteria. Menopausal patients received estrogens
      prior to surgery. Vaginal meshes were used only in patients with grade III and IV
      cystocele. The patients were followed up at 1 1/2, 6, 12 and 36 months (first
      local evaluation for meshes at 2 weeks after surgery). RESULTS: During the study
      interval 400 patient with a mean age of 57.45 +/- 5 years (range 29-81 years)
      were surgically treated in our clinic. Of these, 150 women underwent classic
      surgery, 243 women transobturator tape procedure-TOT (107 TOT alone for SUI and
      136 TOT combined with classic surgery), 4 women ten- sion-free vaginal tape (TVT)
      procedure, and 3 patients prepubic and transobturator mesh. In 12 patients meshes
      with 2 or 4 arms for cystocele (7 and 5 cases, respectively) were used. Vaginal
      mesh extrusion was recorded in 4 patients. CONCLUSIONS: The use of prostheses
      allows a better standardization of procedures, shortening of surgical time and a
      better postoperative recovery, the patients being able to resume their normal
      activities.

PMID- 25970959
TI  - Clinico-epidemiological study of endometrial hyperplasia--a risk factor for the
      development of endometrial carcinoma?
AB  - AIM: Metaplasia is defined as a transformation of an adult epithelial or
      conjunctive cellular type into another adult cellular type. Endometrial
      hyperplasia and particularly complex atypical hyperplasia exposes to a high risk
      of development of the endometrial carcinoma, being considered a lesion precursory
      to the same. Endometrial hyperplasias are risk factors for the development of
      endometrial carcinoma and their prophylaxis implies their accurate diagnosis,
      taking into account that the adenocarcinomas diagnosed in an advanced stage,
      whose therapeutic context differs from the early stages, have a much lower chance
      of survival. MATERIAL AND METHODS: Our study aimed at highlighting objective
      criteria in establishing the morphological diagnosis and in evaluating the
      prognostic elements. The studied batch included 875 patients with endometrial
      hyperplasia and 263 patients with endometrial adenocarcinoma, who were admitted
      between 2003 and 2007, and the histopathologic diagnosis was obtained by
      processing the hysterectomy pieces. The presence of this tumour was at its
      highest level half-way through the study, which was in 2005. RESULTS: According
      to the study, there was a higher proportion of patients with endometrial
      carcinoma from the urban environment (58.2%) than the ones from the rural
      environment (only 41.8%). Depending on their age, most cases of endometrial
      adenocarcinoma were diagnosed in 53-year old patients, with an average age of
      58.94 years. Our study, made of the two batches of endometrial adenocarcinomas,
      shows that between the endometrial and non-endometrial adenocarcinoma there are
      significant differences related to the patients' age, the morphological aspect of
      the carcinoma, the architectural degree, the nuclear degree of tumours and the
      invasion in the myometrium. CONCLUSIONS: Our study proves that endometrial
      hyperplasia is a frequent diagnosis in peri- and postmenopausal patients and is
      frequently identified following investigations for an abnormal uterine bleeding.
      The age of patients with endometrial carcinoma is an important prognostic factor
      independent of other parameters. The difference between complex hyperplasia with
      no atypias and complex hyperplasia with atypias is important, because atypical
      complex hyperplasia is considered the precursor of endometrial adenocarcinoma.

PMID- 25970960
TI  - Meckel's diverticulum--a rare cause of intestinal obstruction in adults.
AB  - Although many people have Meckel's diverticulum, only some experience any
      symptoms, most under the age of 10. In adults it is usually asymptomatic but
      approximately 4% develop complications. Meckel's diverticulum is usually
      diagnosed in the first years of life and after that the risk of the complications
      decreases with increasing age, with no predictive factors for the development of
      complications. We describe the case of a 34-year-old man admitted in the
      emergency department with diffuse abdominal pain, nausea, flatulence and lack of
      transit for feces and gas. The patient had been previously operated for
      peritonitis due to a perforated ulcer. Clinical examination and paraclinical
      investigations (abdominal radiography and ultrasound) suggested the diagnosis of
      intestinal obstruction, probably produced by adhesions due to previous abdominal
      intervention. The diverticulum was resected using a linear stapler and the
      patient recovered without any complications. Small bowel obstruction due to
      Meckel's diverticulitis may be caused by entangled loop of small bowel around a
      fibrous cord, intussusception, volvulus, or incarceration within a hernia sac.
      The discovery of a Meckel's diverticulum complication in a mid thirties patient
      represented an intra-operatory surprise and is the peculiarity of the case.

PMID- 25970961
TI  - Emphysematous cystitis: an unreported complication after pancreaticoduodenectomy.
AB  - Pancreaticoduodenectomy was associated with an increased morbidity, and septic
      complications are the primary cause of death in these patients. However, severe
      sepsis, caused by a postoperative urinary tract infection, is uncommon. It is
      presented the case of a 72 years old man, with a pylorus-preserving
      pancreaticoduodenectomy for an ampullary adenocarcinoma. Postoperatively, the
      patient developed a chyle leak, and a severe urinary tract infection (i.e.,
      emphysematous cystitis), with septic shock. The diagnosis, management and outcome
      are discussed. In conclusion, emphysematous cystitis is a potentially life
      threatening complication, which may occur due to the postoperative
      immunodepression after pancreaticoduodenectomy.

PMID- 25970962
TI  - Pelvic endometriosis and uretero-hydronephrosis: clinical, imagistic and surgical
      implications--case report.
AB  - Endometriosis represent the presence and proliferation of functional endometrial
      like tissue outside the uterine cavity, and is a chronic, recurrent, debilitating
      desease, in which kidney implications are rare, but complex. OBJECTIVE:
      Evaluation of clinical, imagistic and surgical implications of uretero
      hydronephrosis secondary to recurrent pelvic endometriosis. MATERIAL AND METHODS:
      30 year old patient diagnosed with primary infertility and left ovarian
      endometriosis (treated with classically conservative surgical procedure),
      presented acute onset of obstructive urinary symptoms, requiring internal
      drainage of the upper urinary straight path (Cook probe) for uretero
      hydronephrosis grade III. CT and MRI examination reveals the presence of a
      imprecise pelvic mass incorporating right distal ureter and uretero-bladder
      ostium. RESULTS: In this clinical and laboratory context, classic surgery is
      practicing with right anexectomy and direct right uretero-vesical reimplantation,
      also with psoas bladder-hitch. Histopathological examination confirmed the
      presence of recurrent ovarian endometriosis with right distal ureteral invasion.
      CONCLUSION: Recurent endometriosis, although considered a benign condition, often
      present invasive characters, determining considerable anatomical destructions and
      severe symptoms.

PMID- 25970963
TI  - Life-threatening complications of impacted common bile duct lithiasis. A case
      report.
AB  - Impacted common bile duct (CBD) lithiasis poses therapeutical challenges and
      repeated attempts of removal may result in life-threatening complications. CASE
      REPORT. A 45 year-old female patient was admitted in emergency for right upper
      quadrant abdominal pain and jaundice. Clinical, lab data, abdominal ultrasound
      (US) and cholangio-MRI established the diagnosis of acute cholecystitis and
      obstructive jaundice due to distal CBD lithiasis. Endoscopic retrograde
      colangiopancreatography (ERCP) confirmed the presence of a distal CBD stone but
      extraction failed. The patient was operated on and surgical procedure consisted
      of cholecistectomy, intraoperative cholangiography and a side-to-side choledocho
      duodenal anastomosis was performed because all attempts to extract the stone
      through choledocotomy or duodenotomy and enlargement of endoscopic shincterotomy
      failed. The postoperative course was endangered by a severe pancreatitis, a
      massive upper digestive bleeding and portal vein thrombosis that responded to
      conservative management in the intensive care unit. The patient was discharged
      after 34 days in good clinical condition and approximately 9 months later was
      readmitted electively for an incisional hernia. Apart from this, physical
      examination, lab tests and imagistic studies were normal; the patient was
      operated and rapidly discharged in good condition. In conclusion, the management
      of CBD lithiasis may be a serious challenge both for interventional endoscopists
      and surgeons and require a concerted team effort.

PMID- 25970964
TI  - Intraorbital foreign body.
AB  - Penetrating orbitocranial injuries caused by intraorbital foreign body are a rare
      cause of morbidity being most common among young people. The term intraorbital
      foreign body refers to a foreign body that occurs within the orbit but outside
      the ocular globe. We report the case of a 12-year-old male child who sustained a
      right cranial facial trauma due to accidental fall on a piece of wood, which
      penetrated intraorbitally. Native cranial magnetic resonance imaging (MRI -1.5 T)
      revealed the presence of an intraorbital foreign body, 6 cm long and 1.5 cm wide,
      near the orbital apex. In our patient, early surgical extraction of the foreign
      body had a decisive role on his full recovery. In this case, although a large
      foreign body penetrated the entire length of the orbit, it did not cause damage
      to any intraorbital structure. Vision and right ocular globe function had an
      excellent prognosis.

PMID- 25970965
TI  - The effects of pregabalin on psycho-motor abilities and cognitive processes in
      mice.
AB  - The purpose of our study was the experimental research on the effects of
      pregabalin in two behavioural models in mice. MATERIAL AND METHODS: The
      experiment was carried out with white Swiss mice treated intraperitoneally as
      follows: Group I (Control): distilled water 0.1 ml/10 g body weight; Group II
      (PGB 10): 10 mg/kbw pregabalin; Group III (PGB 20): 20 mg/kbw pregabalin. The
      psychomotor abilities of pregabalin were tested on a LE-8811 Actimeter device
      (Panlab), in order to investigate both global motor behaviour and number of
      escape attempts during an eight-minute interval session. The exploration of
      memory processes performance was assessed using the Y-maze model, based on the
      natural tendency of mice to explore new environment. Data were analyzed using
      SPSS 13.0 for Windows software. The experimental protocols were implemented
      according the guidelines of "Grigore T. Popa" University Committee for Research
      and Ethical Issues. RESULTS: The administration of pregabalin resulted in a dose
      dependent reduction of mice horizontal and vertical movements, statistically
      significant compared to the Control group. The administration of both PGB10 and
      PGB20 induced no modifications of the spontaneous alternation percent; also, it
      did not influence the arm entries number compared to Control group in Y-maze
      test. CONCLUSIONS: The results reflect a significant dose-dependent diminution of
      number of escape attempts, exploratory and self-maintenance spontaneous behavior
      after pregabalin treatment, which could be correlated with an anxiolytic effect.
      Moreover, the study proved that pregabalin did not modify the animal cognitive
      processes performance or influence short-term memory of mice in the Y-maze test.

PMID- 25970966
TI  - Imidazoline receptor antagonists idazoxan and efaroxan enhance locomotor
      functions in rats.
AB  - Discovered in 1984, imidazoline receptors (I1, I2, I3) are located centrally and
      peripherally being involved in various physiologic and pathophysiologic processes
      in the body. Experimental and clinical investigations have suggested the
      interrelations between imidazoline, adrenergic, dopaminergic, glutamatergic and
      opioid systems, which may explain the influence of different substances acting on
      imidazoline receptors in cognitive disorders, behavioral disturbances and motor
      diseases pathways. AIM: To investigate the effects of two imidazoline receptor
      antagonists on locomotor activity and endurance capacity in rats. MATERIAL AND
      METHODS: The experiment was carried out with white male Wistar rats (200-250 g)
      divided into 3 groups of 7 animals each, treated intraperitonealy with the same
      volume of solution as follows: Group I (Control): distilled water 0.3 ml/100 g
      body weight; Group II (IDZ): idazoxan 3 mg/kbw; Group III (EFR): efaroxan 1
      mg/kbw. Exercise capacity was evaluated using a locomotor PanLAB treadmill test.
      The data were presented as mean +/- standard deviation and significance was
      tested by SPSS Statistics for Windows version 17.0 and ANOVA method. Experimental
      protocol was implemented according to recommendations of the Gr.T. Popa"
      University Committee for Research and Ethical Issues. RESULTS: Intraperitoneal
      administration of idazoxan and efarox- an resulted in a significant increase in
      running distance compared with the control group (p < 0.05). At the same time a
      reduction in the number and time of electric shocks delivered to motivate the
      animal to keep running was observed. In this experimental behavioral model the
      effects of idazoxan on the evaluated parameters were more intense than those of
      efaroxan. CONCLUSIONS: In our experimental conditions we demonstrated the ability
      of imidazoline receptor antagonists idazoxan and efaroxan to improve fatigue
      resistance during forced running in rats.

PMID- 25970967
TI  - Confidentiality principles in psychiatry.
AB  - Confidentiality stands out in psychiatry through its multiple connotations as an
      intrinsic necessity in the ethics of professional relationships. Thus it
      represents an important characteristic of this profession and at the same time a
      stringent request which, through its specificity, implies a direct contact with
      persons in need for help. Despite being inserted in professional codes and
      legislative systems, confidentiality in psychiatry is far from being considered a
      clarified matter and does not stand aside from ethical controversy. Keeping the
      professional secret is often a hard task due to the pressure of the law or of
      other professional groups who can bring multiple justifications, including that
      of action for the benefit of society. The therapist is often sub- mitted to a
      tension caused on the one hand by the promise of keeping the professional secret
      and on the other hand by multiple requests of breaking the confidentiality. So
      the problem of confidentiality in Psychiatry deserves special attention because
      in this profession, more than in other branches of medicine, the gain of the
      patient's trust is essential in the psychotherapeutic relationship.

PMID- 25970968
TI  - From punishment to education--juvenile delinquency in Romanian criminal law.
AB  - For centuries children were considered "mini-adults". Together with expressing
      the need to educate children and putting a stop to their integration in the work
      field from the earliest years the 19th century also displayed a new image of the
      child, which clearly separates him from the adults. In this paper the authors
      analyze the Romanian legislation addressing juvenile delinquency in criminal
      temporal evolution. On the one hand the minority age limits are sought and
      modulation of legislative provisions according to these, and on the other hand,
      types of penalties for minors are discussed. The authors conclude that the
      approach to juvenile delinquency in the current Romanian Criminal Code is the
      result of a long process of reflection of the legislators on adopting a different
      system of sanctions for juvenile offenders and on creating special regulations
      concerning the prosecution, trial and enforcement of the decisions regarding
      them.

PMID- 25970969
TI  - Quality of life for amblyopic children and their parents.
AB  - AIM: To highlight the changes in the quality of life in patients with
      anisometric, refractive, strabic and mixed amblyopia and to assess the
      psychosocial implication for their family. MATERIAL AND METHODS: Prospective
      observational transversal study of 44 ambulatory pa- tients (88 eyes) treated in
      the Ophthalmology Clinic of Iasi "Sf. Spiridon" Hospital and Iasi Stereopsis
      Ophthalmology Clinic. Clinical parameters: visual acuity, objective refraction
      (autorefractometry), optical correction type, stage of binocular vision, ocular
      motility, strabic deviation. The patients or their attendants accepted to fill
      out a questionnaire comprising 46 items pertaining to 9 domains to assess patient
      (or parents) adherence to treatment and issues related to quality of life.
      RESULTS: Mean age of study patients was 8.19 +/- 2.92 years (range 4-16 years)
      and age at first diagnosis was: 3.90 +/- 2.15 years. Moderate and severe
      amblyopia in the right eye was present in 47.72% of cases and in the left eye in
      43.18%. Right eye uncorrected visual acuity was 0.45 +/- 0.31 and corrected 0.63
      +/- 0.31 (p < 0.0001). Left eye uncorrected visual acuity was 0.49 +/- 0.33 and
      corrected was 0.69 +/- 0.32 (p < 0.0001). No statistically significant difference
      between the right and left eye were found. A 46-item questionnaire focused on
      child health, visual acuity, binocular vision, time to occlusion or penalization,
      child emotions/activity, family and society integration was used. CONCLUSIONS:
      The first presentation to the ophthalmologist was at age 3.9091 +/- 2.1597 years
      (range 3 months-7 years). Health promotion and education is important to
      determine parents to seek help from an ophthalmologist not later than age 3. The
      main symptoms that led the parents to seek eye care were: strabic deviation-
      45.45%, difficulty seeing the blackboard--11.36%, and difficulty in seeing closer
      -20.45%. Quality life questionnaires detect life or school problems of children
      with amblyopia and educate parents. In 15.91% of parents they did not knew that
      before treatment the child had poor school results. This study represents the
      first step in Romanian ophthalmologists concern for socio-professional
      integration of children with amblyopia, because as we know some jobs require
      healthy eyes and for those who do not receive appropriate treatment their dream
      will be denied.

PMID- 25970970
TI  - Degree of patient satisfaction with health care performance assesed by marketing
      surveys.
AB  - AIM: Marketing surveys of the health system collect useful information to develop
      effective management strategies. The research aim consisted in measuring patient
      satisfaction with health care quality. MATERIAL AND METHODS: The qualitative
      research was based on an online SurveyMonkey open-ended questionnaire. The
      analysis of patient satisfaction/dissatisfaction with healthcare professionals
      was performed in 1838 patients. Correlation analysis allowed the identification
      of some determinants associated with patient satisfaction. RESULTS: The variable
      most commonly associated with satisfaction was "I got adequate information about
      procedures/treatment" according to 32.2% of respondents. The patients who were
      dissatisfied most commonly complained that they were "Not adequately informed
      about maneuvers and treatment", reported by 40.0% of respondents. CONCLUSIONS:
      This study provides a basis for building an original model for determining the
      variables of an efficient healthcare system which to ensure a high degree of
      patient satisfaction.

PMID- 25970971
TI  - Responsibility and expectations in antiretroviral therapy--patients' versus
      doctors' perspective.
AB  - AIM: This paper aims to uncover what patients really expect form ART, and also
      what infectious diseases doctors expect from a patient's ART regime, thus
      exploring an important side of adherence to ART. MATERIAL AND METHODS: From July
      to November 2014 we have conducted a qualitative study regarding both patients'
      and doctors' expectations form the ART. We interviewed 30 patients and 4 doctors.
      We used semi-structured interviews that were conducted in the Psychosocial
      Compartment of the HIV/AIDS Regional Center in Iasi. RESULTS: The patients we
      interviewed came from all 6 counties in the Moldova area. Age varied from 16
      years to 59 years; 55% were female and 45% male. 30% came from a rural area. The
      most common expectations that patients have regarding ART are: "to help me live",
      "not to make me feel sick", "to be easy to take (not to big, not a lot)", "not to
      show on the outside what I have on the inside". The infectious diseases doctors
      that we interviewed work in the HIV/AIDS Regional Center in Iasi. Their
      expectations regarding an ART regimen for patients were: "to reduce HIV viral
      load", "to increase CD4 cell count" and "to have minimal impact on the proper
      functioning of other organs". Patients consider themselves the only factors
      responsible for their own ART adherence in 56.6% of cases; 20% consider the
      doctor to be responsible for their adherence, 16.6% feel that their family,
      friends, and spouse are responsible, and 6.6% (2 patients) couldn't answer.
      Infectious diseases doctors considered that patients are 100% responsible for
      adhering to the antiretroviral therapy. CONCLUSIONS: In order to assure adherence
      to the ART it is important to explore both the doctor and the patient's
      perspective and to find ways to find a common ground in building a healthy
      relationship.

PMID- 25970972
TI  - The discontent degree in relations with the proximal social environment and
      adolescent personality features in Timis County, Romania.
AB  - In our study we investigated whether there is a relation between the degree of
      discontent in relations with the proximal social environment (family and peer
      groups) and adolescent personality features. The study was conducted on a
      statistical representative and homogenous sample consisting of 2908 teenagers
      (51.5% girls and 48.5 % boys, aged between 15 and 19 years). It was an
      observational (case) study and it consisted in 2 questionnaires applying:
      Freiburg Personality Inventory (212 items) and CORT 2004 questionnaire (116
      items, 6 referring to the discontent levels created by proximal social
      environment). Cronbach's alpha index was 0.802 for FPI and 0,910 for CORT 2004.
      Statistical analysis was performed by SPSS 16 program applying Chi square (chi2)
      and gamma (gamma) correlation. RESULTS: Depression and Emotional lability
      correlated positively and powerfully with q15 (discontent degree of relations
      with present friend-peers) (gamma = 0.471, Sig. 0.000, and gamma = 0.383, Sig.
      0.000, respectively) and q5 (discontent degree of the relation with parents)
      (gamma = 0.380, Sig. 0.000, and gamma = 0.337, Sig. 0.000, respectively).
      Sociability and calm correlated negative with q5 (gamma = -0.14, Sig. 0.000, and
      gamma = -0.35, Sig. 0.000, respectively), q15 (gamma = -0.33, Sig. 000 and gamma
      = -0.18, Sig. 000, respectively). In conclusion, there is direct proportional
      relation between the discontent degree of relations with friend-peers and parents
      and depression and emotional lability, and inverse proportional relation of
      friend-peers and parents with sociability and calm.

PMID- 25970973
TI  - The influence of premature loss of temporary upper molars on permanent molars.
AB  - AIM: Premature loss of primary molars due to dental caries and their
      complications has been associated with space loss and eruptive difficulties,
      especially when the loss occurs early. The aim of our study was to determine the
      impact of premature loss of temporary upper molars upon the longitudinal axis of
      the first and second upper permanent molar. MATERIAL AND METHODS: The study group
      included 64 patients 6-9 years old with premature loss of primary molars and a
      control group of 48 patients with intact temporary teeth. It was evaluated the
      angle between longitudinal axis of first and second upper permanent molars and
      occlusal plane. The sofware used is Easy Dent 4 Viewer(r).The data were analyzed
      by using the Statistical Package for the Social Sciences (version 20.0; SPSS,
      Chicago, III). RESULTS: It was observed that premature loss of upper second
      deciduous molars modifies greater the vertical axis of the permanent molars than
      the premature loss of first upper primary molar. First upper primary molar loss
      cause an acceleration eruption of first premolar, which will produce a distal
      inclintion of the both permanent molars. CONCLUSIONS: The use of space
      maintainers after premature loss of the second upper temporary molar is a last
      solution in preventing tridimensional lesions in the dental arch and occlusion.

PMID- 25970974
TI  - Young patients' perception on different surgical management of the disto-oclusal
      gingival operculum in second mandibular molars.
AB  - AIM: This baseline study aims to find out the young patients' perception on
      different surgical management of the disto-oclusal gingival operculum in second
      mandibular molars:the conventional technique and the laser assisted one. MATERIAL
      AND METHODS: The current study included a batch of 20 patients who needed
      surgical bilateral removal of the disto-oclusal operculum in second mandibular
      molars order for them to receive conservative treatment. Each patient benefited
      of two different surgical techniques (laser assisted and conventional). Patients'
      perception towards these procedures was evaluated with a simple questionnaire.
      RESULTS: The questionnaires were evaluated by a specialized team and the results
      were illustrated in the specific charts. On one hand the conventional technique
      wasn't perceived as very comfortable and on the other hand the laser assisted
      technique was very well perceived by the patients. CONCLUSIONS: The overall
      perception of young patients towards laser assisted periodontal surgery was very
      high and this is a means of reducing operating time and anxiety caused by the
      surgery itself.

PMID- 25970975
TI  - Reliability and accuracy of three different computerized cephalometric analysis
      software.
AB  - The aim of this investigation was to determine, compare and evaluate three
      different computerized tracing programs, where the lateral cephalograms were
      digitized on the screen. 39 randomly selected cephalometric radiographs were used
      in the present study. Three programs Planmeca Romexis(r) (Romexis 3.2.0.,
      Helsinki, Finland), Orthalis (France) and AxCeph (A.C 2.3.0.74, Ljubljana,
      Slovenia) were evaluated. 12 skeletal, 9 dental and 3 soft tissue parameters were
      measured that consisted of 11 linear and 13 angular measurements. Statistical
      analysis was carried out using multivariate analysis of variance (MANOVA), Levene
      test, Tukey Honestly Significant Difference (HSD) test and Kruskal-Wallis test.
      The measurements obtained with the cephalometric analyses programs used in the
      study were reliable.

PMID- 25970976
TI  - PINUS cembra L: histo-anatomical features, antioxidant enzyme activities and
      heavy metal contents of leaves and long shoots.
AB  - AIM: This study aimed to investigate the histo-anatomical features of the long
      shoots and leaves (young and mature) of Pinus cembra L.. The activity of
      antioxidant enzymatic systems and the content of heavy metals were also
      evaluated. MATERIAL AND METHODS: For the histo-anatomical study, the cross
      sections were performed by usual techniques. The activity of antioxidant
      enzymatic systems (superoxide dismutase, catalase and peroxidase) was evaluated
      by spectrophotometric methods. The content of heavy metals was determined by
      atomic absorption spectroscopy. RESULTS: The cross-section through the long
      shoots shows many resiniferous canals and a periderm of variable thickness. The
      leaf has a triangular shape and only two vascular bundles in the inferior and
      upper levels. The highest level of superoxide dismutase activity (344.90 U/mg
      protein) was determined in the long shoots collected from a cembran pine in Vatra
      Dornei, while the highest level of peroxidase activity (7611.11 U/mg protein) was
      found in the leaves collected in Calimani Mountains. Cd level in all samples was
      under the quantification limit. Higher levels of Pb were determined in the long
      shoots (3 MUg/g dry weight for the vegetal material collected in Vatra Dornei and
      2.86 MUg/g dry weight for the vegetal material collected in Calimani Mountains).
      CONCLUSIONS: Pinus cembra L. leaves show specific elements of subgenus Strobus (a
      triangular shape of the cross section, one single vascular bundle and two
      resiniferous canals). The results obtained for the superoxide dismutase and
      peroxidase activities corroborated with those obtained for the heavy metal
      contents indicate that antioxidant enzymes play an important role in the
      protection of Pinus cembra L. against exogenous stress factors.

PMID- 25970977
TI  - Assessment of the microbial load of some medicinal plants commonly used in
      Romania.
AB  - AIM: This study aims to assess the microbial load of some medicinal plants
      (Matricaria chamomilla, Achillea millefolium, Ocimum basilicum, Calendula
      officinalis, Tilia cordata, Hypericum perforatum) commonly used as medicinal
      teas. MATERIAL AND METHODS: A total of 24 samples collected from the local
      market, as well as from the spontaneous flora of Galati County, were analyzed in
      terms of the total number of germs, the content of coliform bacteria, yeasts and
      molds, and the presence of specific pathogenic bacteria (Escherichia coli,
      Bacillus cereus, Coagulase-positive Staphylococcus, Salmonella spp.). RESULTS:
      The values obtained for total number of germs, yeasts and molds were in
      accordance with the limits set by the European Pharmacopoeia for plant products
      to which hot water is added before use. In the case of specific pathogenic
      bacteria, the presence of E. coli was confirmed in 41.66% of the samples, the
      presence of Coagulase-positive Staphylococcus in 16.66% of the samples, and the
      presence of Bacillus cereus in 33.33% of the samples. Salmonella spp. was absent
      in all samples. CONCLUSIONS: The study highlights a certain microbial load of
      medicinal plants analyzed, emphasizing the importance of quality control in all
      stages of production.

PMID- 25970978
TI  - Armillaria mellea: phenolic content, in vitro antioxidant and antihyperglycemic
      effects.
AB  - Armillaria mellea, known as honey mushroom, has been used both as food and
      medicine. AIM: In this work, the ethanolic and hydromethanolic extracts from
      Armillaria mellea fruiting bodies were investigated for their phenolic content,
      antioxidant and antihyperglycemic effects (in vitro studies). MATERIAL AND
      METHODS: The total phenolics were quantified using Folin-Ciocalteu assay. The
      antioxidant activity was evaluated by testing the free radical scavenging
      capacity, reducing power and ferrous ion chelating ability; in addition, the
      capacity to inhibit 15-lipoxygenase was also assessed. The antihyperglycemic
      activity was investigated by alpha-glucosidase assay. RESULTS: Total phenolic
      contents of 21.68 +/- 0.06 and 5.70 +/- 0.28 mg/g were determined in the
      hydromethanolic and ethanolic extracts, respectively. The hydromethanolic extract
      showed higher free radical scavenging and reducing abilities (EC50 = 452.6 +/-
      2.7, 140.57 +/- 1.45 and 129.45 +/- 0.98 MUg/mL in DPPH, ABTS and reducing power
      assays, respectively). The ethanolic extract proved to be more efficient in the
      ferrous ion chelation, 15-lipoxygenase and alpha-glucosidase inhibition assays
      (EC55 = 67.93 +/- 0.35, 290.93 +/- 2.05 and 8.54 +/- 0.06 MUg/mL, respectively).
      CONCLUSIONS: Armillaria mellea extracts showed antioxidant and antihyperglycemic
      potential in in vitro models and therefore they are promising candidates for the
      development of dietary supplements and pharmaceutical products.

PMID- 25970979
TI  - Analyse of socket-prosthesis-blunt complex for lower limb amputee using objective
      measure of patient's gait cycle.
AB  - The prosthetic application is a highly complex process. Modeling and simulation
      of biomechanics processes in orthopedics is a certainly field of interest in
      current medical research. Optimization of socket in order to improve the quality
      of patient's life is a major objective in prosthetic rehabilitation. A variety of
      numerical methods for prosthetic application have been developed and studied.
      MATERIAL AND METHODS: An objective method is proposed to evaluate the performance
      of a prosthetic patient according to surface pressure map over the residual limb.
      The friction coefficient due to various liners used in transtibial and
      transfemoral prosthesis is taken into account also. RESULTS: Creation of a bio
      based modeling and mathematical simulation allows the design, construction and
      optimization of contact between the prosthesis cup and lack of functionality of
      the patient amputated considering the data collected and processed in real time
      and non-invasively. The von Mises stress distribution in muscle flap tissue at
      the bone ends shows a larger region subjected to elevated von Mises stresses in
      the muscle tissue underlying longer truncated bones. CONCLUSIONS: Finite element
      method was used to conduct a stress analysis and show the force distribution
      along the device. The results contribute to a better understanding the design of
      an optimized prosthesis that increase the patient's performance along with a god
      choice of liner, made by an appropriate material that fit better to a particular
      blunt. The study of prosthetic application is an exciting and important topic in
      research and will profit considerably from theoretical input. Interpret these
      results to be a permanent collaboration between math's and medical orthopedics.

PMID- 25970980
TI  - Microstructural characteristics of tin oxide-based thin films on (0001) Al2O3
      substrates: effects of substrate temperature and RF power during co-sputtering.
AB  - While tin oxides such as SnO and SnO2 are widely used in various applications,
      surprisingly, only a limited number of reports have been presented on the
      microstructural characteristics of tin oxide thin films grown under various
      growth conditions. In this paper, the effects of the substrate temperature and
      content of foreign Zn ion on the microstructural characteristics of tin oxide
      thin films grown by radio-frequency magnetron sputtering were investigated. The
      increase in substrate temperature induced change in the stoichiometry of the thin
      films from SnO(1+x) to SnO(2-x). Additionally, the phase contrast in the
      transmission electron microscopy image revealed that SnO(1+x) and SnO(2-x) phases
      were alternating in thin films and the width of each phase became narrower at
      high substrate temperature. The ternary zinc tin oxide thin films were deposited
      using the co-sputtering method. As the ZnO target power increased, the
      crystallinity of the thin films became poly-crystalline, and then showed improved
      crystallinity again with two types of phases.

PMID- 25970981
TI  - Electrical and electrochemical migration characteristics of Ag/Cu nanopaste
      patterns.
AB  - Since direct printing technology has developed intensively, low-cost fabrication
      and reliability have become critical challenges for mass production of printed
      electronic devices. The silver/copper (Ag/Cu) nanopaste was manufactured by Ag
      nanopaste mixed with different proportions of Cu nanoparticles ranging from 0 to
      5 vol.% in order to investigate the influences of Cu content on the electrical
      properties and electrochemical migration (ECM) characteristics. The patterns were
      constructed on a glass wafer via screen printing with the Ag/Cu nanopaste. They
      were then annealed through debinding for 30 min in air followed by sintering for
      30 min in a hydrogen atmosphere at various temperatures (150, 200, 250, and 300
      degrees C). The electrical resistivity of printed patterns that were sintered at
      150 degrees C grew with increases in the percentage of Cu content in the Ag/Cu
      nanopaste, while printed patterns that were sintered at 300 degrees C show
      similar electrical resistivity values of around 2-3 MUOmega cm regardless of Cu
      content. The ECM characteristics of the printed patterns were evaluated by
      performing a water drop test. The printed patterns that were sintered at higher
      temperatures showed longer ECM times. At 300 degrees C, the ECM time was
      considerably lengthened when the Cu content was over 2 vol.%, and the 5 vol.% Cu
      pattern showed the longest ECM time of 305 s, which was around 1.65 times that of
      the Ag pattern.

PMID- 25970982
TI  - Dielectric and piezoelectric properties of lead-free 0.5Ba(Zr0.2 Ti0.8)O3
      0.5(Ba0.7Ca0.3)TiO3 piezoelectric ceramics with glass additive.
AB  - We have investigated the dielectric and piezoelectric properties of lead-free
      0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 ceramics with BaO-CaO-SiO2 glass additive
      as a function of sintering temperatures. With adding BaO-CaO-SiO2 glass additive,
      diffusivity of lead-free 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 ceramics was
      increased. The dispersion constant gamma of BZT-BCT ceramics with BaO-CaO-SiO2
      glass was changed from 1.9683 to 1.7673 by decreasing sintering temperature
      ranging from 1450 degrees C to 1350 degrees C, while 0.5Ba(Zr0.2Ti0.8)O3
      0.5(Ba0.7Ca0.3)TiO3 ceramics at sintered 1450 degrees C showed gamma = 1.5055.
      The piezoelectric properties such as electromechanical coupling factor (k(p)) and
      piezoelectric constant (d33) of lead-free 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3
      ceramics with BaO-CaO-SiO2 glass additive sintered at 1400 degrees C showed
      similar values compared with 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 ceramics
      without BaO-CaO-SiO2 glass additive sintered at 1450 degrees C. The addition of
      BaO-CaO-SiO2 glass additive can be of help to decrease sintering temperature of
      lead-free 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 ceramics.

PMID- 25970983
TI  - The synthesis of Pt/Ag bimetallic nanoparticles using a successive solution
      plasma process.
AB  - A successive solution plasma process was developed for the synthesis of Pt/Ag
      bimetallic nanoparticles. Ag nanoparticles were made first by applying a high
      voltage of bipolar pulsed DC to anode and cathode electrodes composed of Ag rods.
      The solution containing Ag nanoparticles was discharged successively using Pt
      electrodes. The joule heating and electrolysis between electrodes generated
      vapors, and solution plasma was sustained due to progressive ionization and
      excitation in the vapor phase. The maximum current and voltage breakdown was
      observed at approximately 8.9 A and 900 V with an interval of 25 MUs, which
      indicated that an intense solution plasma was sustained continuously. The Pt-on
      Ag heterogeneous nanostructures formed, and finally, the Ag nanoparticles were
      completely covered by Pt nanoparticles after a discharge duration of 1,200 s.

PMID- 25970984
TI  - Co-Ni alloy nanowires prepared by anodic aluminum oxide template via
      electrochemical deposition.
AB  - The alloy nanowires are more prospective magnetic and shape memory materials.
      Fabrication of binary or more alloy nanowires using electrochemical deposition
      process is generally challenging due to the different synthesis conditions of
      individual elements. In the present work, binary NiCo alloy nanowire arrays have
      been fabricated by electrochemical deposition using anodic aluminum oxide
      template medium technique. The optimum conditions (temperature, voltage and time)
      for synthesis of NiCo alloy nanowire array were achieved based on the ideal
      experimental conditions of single Ni and Co nanowire arrays. The synthesized NiCo
      alloy nanowire arrays were characterized by X-ray diffraction, field emission
      scanning electron microscopy and energy dispersive X-ray spectrometer. The
      amorphous NiCo alloy nanowires were crystallized by annealing of 800 degrees C
      for 1 hour in argon atmosphere. The controlled composition of electrolyte
      provided to achieve a uniformly distributed chemical composition of Ni and Co
      (49.26:50.74) in nanowires.

PMID- 25970985
TI  - Annealing-dependent electrical properties of Ga-doped ZnO film on silicon
      carbide.
AB  - The effect of substrate temperature and thermal annealing on the structural,
      electrical, and optical properties of Ga-doped zinc oxide (GZO) thin films were
      examined for use as transparent electrodes on silicon carbide (SiC). The
      variation of these properties is thought to be related to the presence and
      stability of Ga3+ ions substituted into Zn2+ sites and adsorbed oxygen ions in
      GZO thin films, as well as the interfacial thickness of GZO/SiC. GZO thin film
      deposited at 400 degrees C without annealing has the lowest resistivity of - 1.96
      x 10(-4) Omega x cm, which increased after annealing. The photosensitivity of
      GZO/SiC was increased with increased substrate temperature (from 1.51 to 6.87%)
      and after annealing (from 2.78 to 8.67%). These results were clarified by
      comparatively analyzing the chemical composition ratio of oxygen in the GZO thin
      films and the interfacial thickness between GZO/SiC.

PMID- 25970986
TI  - Thermochromic properties of Sn, W co-doped VO2 nanostructured thin film deposited
      by pulsed laser deposition.
AB  - Tin (Sn) and tungsten (W) co-doped vanadium dioxide (VO2) nanostructured thin
      films with 50-nm thickness were deposited by pulsed laser deposition (PLD) to
      reduce the transition temperature and improve the IR transmittance. The crystal
      structure of the nanostructured thin films and the presence of elements were
      evaluated by XRD and XPS analysis. The transition temperature (T(c)) of 1 at% Sn
      1 at% W co-doped VO2 nanostructured thin film was decreased to about 22 degrees C
      (from 70.3 to 48.5 degrees C) compared with the undoped VO2 nanostructured thin
      film. The transmittance width in the IR range of the co-doped nanostructured thin
      film decreased from 37.5% to 27% compared with the undoped VO2 nanostructured
      thin film. Also, the width of hysteresis was narrowed by Sn doping.

PMID- 25970987
TI  - CrAIN film deposited by magnetron sputtering for the inkjet printer head.
AB  - CrAIN film has advantages of stability and multifunctionality over the commercial
      TaN0.8. This study investigated the characteristics of CrAIN film deposited by
      radio frequency magnetron sputtering as a function of Al content after deposition
      heat treatment. With a 600 degrees C heat treatment and 20% Al content, the low
      temperature coefficient of resistance (-2670.6 ppm/k), high oxidation resistance,
      and thermal conductivity were acquired. This was found due to the high-density
      columnar NaCI structure with 20% Al and the recrystallization utilized by heat
      treatment.

PMID- 25970988
TI  - Fabrication and characteristics of hexagonal Zn nanowires prepared by heating a
      mixture of Zn and graphite powders.
AB  - We report the fabrication of thin (< 100 nm) hexagonal Zn nanowires in a
      conventional reactor, by heating a mixture of Zn and graphite powders. By
      material characterization, the products were identified as one-dimensional
      nanowires of serpent-like morphology with a hexagonal Zn phase. The main growth
      mechanism of the Zn nanowires was proposed to be a vapor-solid process, which was
      corroborated by the absence of any tip catalyst. Raman spectra of the Zn
      nanowires exhibited a prominent peak at around 570 cm(-1). X-ray photoelectron
      spectroscopy revealed that the surface of the Zn nanowires was clearly oxygen
      deficient in comparison to that of ZnO nanowires. Photoluminescence analysis
      indicated that the Zn nanowires exhibited emission bands centered at 1.6, 2.0,
      2.4, 3.0, and 3.3 eV, respectively.

PMID- 25970989
TI  - Development of thermal runaway preventing ZnO varistor for surge protective
      device.
AB  - In this paper, the centre of electrode is suggested for heat conduction.
      Therefore, the specific reflow soldering process is needed. The comparison of
      temperature difference among the different areas of ZnO varistors is analyzed.
      With the nominal surge current, thermal behavior is analyzed. The operation point
      of temperature for disconnection is proposed. Accordingly, the thermal runaway
      preventing ZnO varistors were covered with a fusible alloy, i.e., a thermal fuse,
      in the process of manufacture, which is expected to ensure there the liability of
      being resistant to lightning discharge and to ensure stability against thermal
      runaway in the failure mode. Additionally, it is expected to reduce much more
      limit voltage than the existing products to which the fuse was separately
      applied. The thermal runaway-preventing ZnO varistor of the surge protection
      devices can be widely used as part of the protection provisions of lightning
      discharge and surge protection demanded in connection with power IT about Green
      Growth which is nowadays becoming the buzzword in the electric power industry.

PMID- 25970990
TI  - Characterization of sulfonated silica nanocomposite electrolyte membranes for
      fuel cell.
AB  - Sulfonated poly(arylene ether sulfone) (SPAES) and sulfonated silica (silica
      SO3H) prepared via sol-gel reaction are used as an organic polymer matrix and
      inorganic nanoparticles. The contents of the silica-SO3H particles in the
      composite membranes are controlled at 0.5, 1, 2, 3 and 5 wt.% in order to
      evaluate the appropriate content for high proton conductivity. Randomly dispersed
      silica particles are obtained from all composite membranes as a result of the
      hydrophilic domains in the polymer and silica-SO3H. In this study, the optimum
      silica-SO3H content for high proton conductivity is 3 wt.% in fully hydrated
      conditions and 0.5 wt.% in low humidity conditions.

PMID- 25970991
TI  - Colored polystyrene particles with a surface charge influenced by suspension
      polymerization.
AB  - Blue polystyrene (PS) particles copolymerized with poly (ethylene glycol) ether
      methyl methacrylate (PEG-MA, Mn = 300, 475, 950) were prepared by suspension
      polymerization in this study. 0-10 wt% PEG-MA was copolymerized with 100-90 wt%
      styrene by suspension polymerization. These blue PS particles were characterized
      using SEM, IR, UV, DSC, and zeta potential measurements. The T(g) data results
      for the suspension copolymers and a solubility test in THF along with the
      matching IR spectroscopy results showed that copolymerization proceeded during
      the polymerization process. The poly[styrene-co-(PEG-MA)] latices were 30-60 nm
      in size, with T(g) values of 341-385 degrees K, zeta- potential values of 51.5
      162 mV, and electrophoretic mobility values ranging from 3.3 to 10.9 x 10(-6)
      cm2/Vs. Blue dye incorporated into the polystyrene particles existed at levels
      that exceeded 85% based on the UV absorbance results.

PMID- 25970992
TI  - Correlation between nano-scale microstructural behavior and the performance of
      ZnO thin-film transistors.
AB  - Binary ZnO active layers possessing a polycrystalline structure were deposited
      with various argon/oxygen flow ratios at 250 degrees C via sputtering. Then ZnO
      thin-film-transistors (TFTs) were fabricated without additional thermal
      treatments. As the oxygen content increased during the deposition, the preferred
      orientation along the (0002) was weakened and the rotation of the grains
      increased, and furthermore, less conducting films were observed. On the other
      hand, the reduced oxygen flow rate induced the formation of amorphous-like
      transition layers during the initial growth due to a high growth rate and high
      energetic bombardment of the adatoms. As a result, the amorphous phases at the
      gate dielectric/channel interface were responsible for the formation of a hump
      shape in the subthreshold region of the TFT transfer curve. In addition, the
      relationship between the crystal properties and the shift in the threshold
      voltage was experimentally confirmed by a hysteresis test.

PMID- 25970993
TI  - Enhanced low-temperature power density of solid oxide fuel cell by nickel
      nanoparticle infiltration into pre-fired Ni/yttria-stabilized zirconia anode.
AB  - The Ni/yttria-stabilized zirconia (YSZ) anode morphology of an anode-supported
      solid oxide fuel cell (SOFC) unit cell was improved by nickel nanoparticle
      infiltration. A colloidal route was selected for efficient fabrication of nickel
      metal nanoparticles and subsequent infiltration into the Ni/YSZ anode of a pre
      fired SOFC unit cell. The power density of the anode-supported SOFC unit cell was
      measured by the potentiostatic method to investigate the effect of nickel
      nanoparticle infiltration. The increase in the power density of the Ni/YSZ anode
      with nickel nanoparticle infiltration became gradually less significant as the
      SOFC operating temperature increased from 700 to 800 degrees C. The improved
      performance of the Ni/YSZ anode with nickel nanoparticle infiltration compared to
      that of an anode without nickel nanoparticles is tentatively attributed to two
      factors: The discretely distributed nanoparticles on the nanostructured
      electrodes exhibited significant catalytic effects on the electrochemical
      performance of the electrodes, in addition to substantially increasing the triple
      phase boundary lengths.

PMID- 25970994
TI  - Effect of sputtering power on structural and optical properties of radio
      frequency-sputtered In2S3 thin films.
AB  - In this study, we investigated the structural and optical properties of indium
      sulfide (In2S3) thin films as a substitute for the CdS buffer layer in
      Cu(In,Ga)Se2 (CIGS) solar cells. The In2S3 films were deposited on glass
      substrates using radio frequency (RF) magnetron sputtering. The sputtering power
      was changed from 60 to 120 W in 20 W increments. The effects of sputtering power
      on the crystallinity, surface morphology, and optical properties of the films
      were characterized with X-ray diffraction (XRD), atomic force microscopy (AFM),
      energy dispersive X-ray spectroscopy (EDS), and UV-visible spectrophotometry. The
      XRD analyses indicated that the films were polycrystalline beta-In2S3 structures
      with two preferred orientations along the (103) and (206) directions. The AFM
      images revealed that the films had nanosized grains and that the size increased
      from 7 nm for the samples prepared at 60 W to 13 nm for those prepared at 120 W.
      The optical band gap of the samples was found to vary between 2.88 and 2.43 eV.

PMID- 25970995
TI  - Electrical and optical properties of Eu-doped indium oxide thin films deposited
      by radio-frequency magnetron sputtering.
AB  - Eu-doped In2O3 (EIO) thin films were deposited by radio-frequency magnetron
      sputtering on glass substrates with varying growth temperatures. All the EIO thin
      films showed a significant dependence on the growth temperature. From the figure
      of merit index data, the optimum growth temperature for depositing high-quality
      EIO thin films was found to be 300 degrees C. The ELO thin film deposited at 300
      degrees C showed a highly preferential growth orientation along the (222) plane
      with an average particle size of 160 nm, bandgap energy of 3.94 eV, average
      optical transmittance of 65.2% in the wavelength range 450-1100 nm, and
      electrical resistivity of 2.5 x 10(-3) Omega cm. These results indicate that the
      electrical and optical properties of EIO thin films can be modulated by
      controlling growth temperature.

PMID- 25970996
TI  - Silicon interposer BGA package with a Cu-filled through silicon via and a
      multilayer redistribution layer fabricated via electroplating.
AB  - As large-scale integrated circuit chips become smaller, conventional organic
      buildup substrates can no longer support them. To resolve this problem, silicon
      interposers with through silicon via (TSV) technology are gaining recognition as
      alternative solution to provide high-density interconnection, improved electrical
      performance due to shorter interconnection from the die to substrate for nano
      scale devices. In this study, we fabricated a silicon interposer to achieve high
      density and high performance packages. Via holes were etched via the Bosch
      process using a deep reactive ion etcher and SiO2 formed with a diffusion furnace
      as the diffusion barrier of the Cu electrode. TSVs were filled with Cu under
      various electroplating conditions. After Cu filling, a Cu post was formed
      directly using the over-filled Cu electrode through a chemical mechanical
      polishing process. A double-layer redistribution layer was formed on one side of
      the interposer using a lift-off process. Sn-3.5% Ag solder bumps 40 MUm in
      diameter were formed directly on the Cu post on another side of the interposer
      using electroplating and the reflow method.

PMID- 25970997
TI  - Metal nitride coatings by physical vapor deposition (PVD) for a wear resistant
      aluminum extrusion die.
AB  - The purpose of this study is to investigate the friction and wear behaviors of
      CrN, TiN, CrAlN, and TiAIN coated onto SKD61 for application to Al 7000 series
      extrusion dies. On the wear test, the experimental parameters are the load and
      the counter material's temperature. The results showed that the friction
      coefficient increased with load but decreased with the counter material's
      temperature, and the friction coefficients of CrN and CrAIN were lower than the
      friction coefficients of TiAIN and TIN, especially at a higher temperature. The
      wear track with different coatings identified different wear behaviors; the wear
      behavior of CrAIN was found to be abrasive, but the wear behavior of TiN, CrN,
      and TiAIN was adhesive. Therefore, CrAIN showed the least wear loss with a lower
      friction coefficient and less adhesion with counter materials at the highest
      range of wear load and temperature. This resulted in the easy formation of
      aluminum oxide in the wear track and less Al adhesion; moreover during the hard
      second phase, AIN dispersed in the film during deposition.

PMID- 25970998
TI  - Characterization of silicon-germanium epitaxial layer by photoluminescence
      intensity and reflectance measurement techniques.
AB  - Si(1-x)Ge(x) epitaxial layers with various Ge fractions sample were characterized
      by photoluminescence intensity method at room temperature. Photoluminescence
      intensity was affected by minority carrier lifetime, defect density, and surface
      condition. PL intensity profile showed misfit dislocation on epitaxial layer for
      15%, 21%, 24%, and 26%, since dislocations were one of minority carrier lifetime
      degradation parameters. It clearly showed misfit dislocation profiles, cross
      hatch, and PL intensity was low at dislocation region.

PMID- 25970999
TI  - Quality dependence of vapor phase-polymerized poly(3,4-ethylenedioxythiophene)
      nanofilm on substrate pre-treatment methods.
AB  - The quality of a vapor phase-polymerized PEDOT thin film is highly dependent upon
      a uniform coating of an oxidant such as Fe(III)Cl3 on a SiO2 surface. The phase
      states of a coated oxidant solution are deeply affected by the surface character
      of base substrates, which can be altered via various pre-treatment methods.
      Therefore, in this study, in order to identify the optimum surface pre-treatment
      method, four different pre-treatment techniques (Ar plasma, O2 plasma, H2O/Ar
      plasma, and a SC-1 treatment methods), were carried out on a thermally oxidized
      Si-wafer surface using a uniform oxidant solution coating. And then, PEDOT films
      were grown on the oxidant coated surfaces using a vapor phase polymerization
      method. Those films were further analyzed using several thin film analyzing tools
      such as a contact angle analyzer, FE-SEM, an optical microscope, FT-IR, and a
      four point probe. From this analysis, it was discovered that the quality of a
      PEDOT thin film can be deeply affected by the surface pre-treatment method. In
      particular, a H2O/Ar plasma-treated SiO2 surface was the most uniformly coated
      with the oxidant solution, and the PEDOT thin films grown on the SiO2 surface
      showed a quite low sheet resistance value (543.84 Omega/sq). Such a high quality
      ultrathin film could be a potential candidate for a transparent flexible
      electrode for the next-generation of display and/or photovoltaic devices.

PMID- 25971000
TI  - Magnetism and magnetocrystalline anisotropy of 3dtransition metal monolayers on
      Pt(001): a density-functional study.
AB  - We systematically investigate the effects of having Pt as a substrate and/or
      capping layer on the magnetism and magnetocrystalline anisotropy (MCA) of 3d
      transition metal (TMs; Cr, Mn, Fe, and Co) monolayers (MLs) by using a first
      principles calculationl method. We found that Fe and Co MLs are ferromagnetic
      (FM) on a Pt(001) surface, but Mn and Cr MLs are antiferromagnetic (AFM). The
      magnetic moments are quite robust with additional Pt-capping. Furthermore, Pt
      capping enhances the small perpendicular MCA (meV) of Fe/Pt(001) significantly to
      4.44 meV. Our electronic structure analyses indicate that strong hybridization
      between Pt-5d and TM-3d orbitals plays a crucial role in determining magnetic
      ordering and MCA. For comparison we also calculated magnetism and MCA of 3d TM
      MLs on Ta(001) with and without Ta-capping.

PMID- 25971001
TI  - AC impedance behaviors of electrochemically deposited Si-hydroxyapatite films on
      nanotube-formed Ti-Nb-Zr alloys.
AB  - The aim of this study was to investigate the AC impedance behaviors of
      electrochemically deposited Si-hydroxyapatite (HA) films on nanotube-formed Ti-Nb
      Zr alloys by the cyclic voltammetry method. Surface modifications were carried
      out sequentially during nanotube formation and the application of Si-HA coatings.
      The nanotube surface formed at 10 V had a smaller diameter than that of the
      nanotube surface formed at 20 V, and the nanotube surface formed at 20 V had a
      denser pore structure as compared to the nanotube surface formed at 10 V. The Si
      HA coating of nanotube surfaces formed at 10 V exhibited flower- and plate-like
      layers, and the nanotube surface formed at 20 V had larger flower- and plate-like
      shapes. After 30 deposition cycles, the Si-HA coating showed more rod-like shapes
      than after 10 deposition cycles. Higher intensity HA peaks were detected after 30
      deposition cycles than after 10 deposition cycles. The Ca/P ratio increased with
      increasing numbers of deposition cycle, and the highest Si percent appeared after
      30 deposition cycles. The polarization resistance values commonly decreased more
      on the nanotube surface formed at 20 V than on the nanotube surface formed at 10
      V, and the values also decreased after Si-HA deposition.

PMID- 25971002
TI  - Effects of temperature, target/substrate distance, and background pressure on
      growth of ZnO nanorods by pulsed laser deposition.
AB  - The growth of ZnO nanorods on the c-plane of Al2O3 substrates by PLD was been
      investigated by controlling processing conditions such as growth temperature,
      distance between target and substrate, and background oxygen pressure. ZnO
      nanorods were observed from the growth temperature of 600 degrees C for the
      oxygen pressure of 30 mTorr and the target/substrate distance of 70 mm. The
      diameters of the ZnO nanorods at the temperature of 700 degrees C and the oxygen
      pressure of 30 mTorr were approximately 200, 70, and 40 nm for the distance of
      45, 70, and 100 mm, respectively. ZnO films without nanorods were observed at the
      distance of 70 mm and the temperature of 700 degrees C when the oxygen pressure
      decreased to 1 mTorr. The kinetic energy of the ablated particles by the laser
      decreases during collisions with background oxygen molecules, resulting in
      conditions that favor the growth of ZnO nanorods.

PMID- 25971003
TI  - Light assisted room temperature ethanol gas sensing of ZnO-ZnS nanowires.
AB  - ZnO-core/ZnS-shell nanowires were synthesized by the thermal evaporation of a
      mixture of ZnO and graphite powders followed by the thermal evaporation of ZnS
      powders. Multiple networked nanowire gas sensors were then fabricated using the
      core-shell nanowires. The morphology, crystal structure and sensing properties of
      the ZnO-core/ZnS-shell nanowires to C2H5OH gas at room temperature under
      ultraviolet (UV) illumination were examined. The responses of the ZnO-core/ZnS
      shell nanowires to C2H5OH gas were 1.2-2.1 times higher than those of the ZnO
      nanowires at C2H5OH concentrations ranging from 50 to 250 ppm under UV
      illumination. On the other hand, the resistance of the ZnO nanowires in the dark
      at room temperature was too high to measure. The underlying mechanism for the
      enhanced gas sensing properties of the ZnO-core/ZnS-shell nanowires toward C2H5OH
      gas is discussed.

PMID- 25971004
TI  - Influence of oxygen concentration on mechanical properties of molybdenum powder
      during sintering.
AB  - In this study, the influence of oxygen concentration on the mechanical properties
      of sintered bodies produced from commercial and low-oxygen molybdenum powder via
      pulsed-current-activated sintering was determined. The hardness of the sintered
      bodies increased with the sintering temperature up to 1,500 degrees C and then
      decreased with further temperature increase. The hardness of the sintered low
      oxygen-molybdenum body was slightly higher than the rest of the sintered bodies.
      This was because the relative density of the sintered low-oxygen-molybdenum body
      increased more than that of others as the sintering temperature increased.
      Furthermore, the grain size of the sintered commercial-molybdenum body was larger
      than that of the sintered low-oxygen-molybdenum body. This was attributed to the
      positive effect of molybdenum oxide on grain growth during sintering. Thus, it
      was established that low-oxygen molybdenum powder can suppress grain growth
      during sintering, resulting in improved mechanical properties of the sintered
      bodies.

PMID- 25971005
TI  - 3-D ordered mesoporous Cd(x)Zn(1-x)S ternary compound semiconductors with
      controlled band gap energy.
AB  - Ordered mesoporous Cd(x)Zn(1-x)S ternary compound semiconductors were prepared
      with a simple nano-casting method using 3-D cubic Ia3d meso-structured silica,
      KIT-6, as a hard-template with the easily available precursors of 3CdSO4 x 8H2O
      and ZnSO4 x 7H2O. Thermal reduction of impregnated precursors resulted in the
      crystalline networks within the mesopore of the silica template, then the ordered
      mesoporous Cd(x)Zn(1-x)S materials were obtained by etching the silica template
      with NaOH aqueous solution. The synthesized Cd(x)Zn(1-x)S materials exhibit high
      surface area, uniform pore size, single gyroidal tetragonal I41/a meso-structure,
      crystalline framework, and finely tuned band gap energies by controlled chemical
      composition.

PMID- 25971006
TI  - Nickel powders recycled from invar scrap by magnesiothermic reduction.
AB  - A study on the recovery of nickel from Fe-Ni alloy scrap was conducted using
      molten magnesium by dissolving only Ni component and then removing Mg using
      vacuum distillation method. The recovering faction of nickel higher than 99% was
      achieved at temperatures above 1,073 K and 99.5% of purity level of nickel was
      successfully obtained under vacuum degree of 10(-5) torr at temperatures above
      1,273 K. The purity, phase, and recovery rate of nickel were examined by scanning
      electron microscopy, elemental analyser, and X-ray diffraction.

PMID- 25971007
TI  - Compositionally graded Ti-Ni alloys prepared by diffusion bonding.
AB  - A Ti-Ni alloy compositionally graded along the thickness direction in order to
      obtain a shape change over a wide temperature range, which is beneficial to the
      actuator for precise position control, was prepared by spark plasma sintering
      (SPS) after stacking Ti-Ni alloy ribbons in the sequence of Ti-51Ni, Ti-50Ni, Ti
      49Ni and Ti-48Ni (at%) followed by annealing. Then, the microstructure and
      martensitic transformation behavior were investigated by using FE-SEM, DSC and
      thermal cycling tests under a constant load. The inter-ribbon defects observed
      after SPS due to insufficient diffusional bonding between the ribbons were
      eliminated by post-SPS annealing at 1023 K for 36 ks. The compositionally graded
      sample showed compositional variation of 1.5 at% Ti along the thickness direction
      (- 120 MUm) and a martensitic transformation temperature window as large as 91 K
      on cooling and 79 K on heating. A recoverable elongation of 0.9% was obtained
      under a stress of 80 MPa and the deformation rate, which is defined as the ratio
      of the recoverable elongation to the temperature range where the elongation
      occurred was 0.015%/K in the compositionally graded sample.

PMID- 25971008
TI  - Depletion effect of oxide semiconductor analyzed by Hall effects.
AB  - This letter discusses the tunneling behavior of amorphous indium-gallium-zinc
      oxide (a-IGZO) analyzed through the observation of its Hall effects. The
      properties of the a-IGZO changed from those of a majority carrier to those of a
      minority carrier after the annealing process as a result of the electron-hole
      recombination due to the thermal activation energy and the formation of a
      depletion layer with a high-potential Schottky barrier. Therefore, the diffusion
      current of these minority charge carriers caused ambipolar transfer
      characteristics, a tunneling behavior, in the metal-oxide semiconductor (MOS)
      transistor.

PMID- 25971009
TI  - Thermo-electrical properties of composite semiconductor thin films composed of
      nanocrystalline graphene-vanadium oxides.
AB  - This paper presents an experimental comparative study involving the
      characterization of the thermo-electrical and structural properties of graphene
      based vanadium oxide (graphene-VOx) composite thin films on insulating and
      conducting surfaces (i.e., fused quartz and acrylic resin-impregnated graphite)
      produced by a sol-gel process via dipping-pyrolysis. A combination of FE-SEM and
      XPS analyses revealed that the graphene-VOx composite thin films (coated onto
      fused quartz) exhibiting the microstructure of 2-graded nanowire arrays with a
      diameter of 40-80 nm were composed of graphene, a few residual oxygen-containing
      functional groups (i.e., C-O and C=O), and the VO2 Magneli phase. The temperature
      dependent electrical resistance measured on the as-deposited thin films clearly
      demonstrated that the graphene-VOx composite nanowire arrays thermally grown on
      fused quartz act as a semiconductor switch, with a transition temperature of 64.7
      degrees C in the temperature range of -20 degrees C to 140 degrees C, resulting
      from the contributions of graphene and graphene oxides. In contrast, the graphene
      VOx composite thin films deposited onto acrylic resin-impregnated graphite
      exhibit a superlinear semiconducting property of extremely low electrical
      resistance with negative temperature coefficients (i.e., approximately four
      orders of magnitude lower than that of the fused quartz), despite the similar
      microstructural and morphological characteristics. This difference is attributed
      to the synergistic effects of the paramagnetic metal feature of the tightly
      stacked nanowire arrays consisting of hexagonal V2O3 on the intrinsic electrical
      properties of the acrylic resin-impregnated graphite substrate, as revealed by FE
      SEM, EDX, AFM, and XRD measurements. Although the thermo-sensitive electrical
      properties of the graphene-VOx composite thin films are very substrate specific,
      the applicability of graphene sheets can be considerably effective in the
      formation of highly planar arrays of VOx nanowires to enhance carrier transport.

PMID- 25971010
TI  - Ablation of graphene film by direct Nd:YVO4 laser under various beaming
      conditions.
AB  - Recently, graphene is gaining increasing popularity as one of the most functional
      materials for advanced electronic and optical devices owing to its high carrier
      mobility and optical transparency. Patterning the graphene calls for particular
      cares in line definition without carbon (C)-based residues that might be working
      as a leakage path. Thus, realization and processing of the graphene monolayer are
      very complicated and need to be stringently controlled. For this reason, in
      accordance, processing technology should be evolved with higher reliability and
      accuracy, and compatibility with the conventional unit processes including
      electron beam (e-beam) lithography, plasma etching, and nano-dimensional optical
      lithography. In this work, a reliable, simple, and cost-effective technique for
      patterning the graphene is proposed. Graphene film transferred on glass substrate
      is directly patterned by a quality factor (Q)-switched neodymium-doped yttrium
      vanadate (Nd:YVO4, lambda = 1064 nm) pumped laser diode (LD). In order to
      optimize the process condition, various beaming conditions of repetition rate and
      scanning speed are experimented. From the optical microscope images, it has been
      shown that graphene film was more easily etched by direct laser patterning
      technique at higher repetition and faster scanning speed. It was confirmed by
      Raman spectrum where 2-dimensional (2-D) and graphite (G) peaks were closely
      investigated that graphene residue was also completely removed after the proposed
      processing technique.

PMID- 25971012
TI  - Sulfonated graphene oxide/nafion composite membrane for vanadium redox flow
      battery.
AB  - Nafion is the most frequently used as the membrane material due to its good
      proton conductivity, and excellent chemical and mechanical stabilities. But it is
      known to have poor barrier property due to its well-developed water channels. In
      order to overcome this drawback, graphene oxide (GO) derivatives were introduced
      for Nafion composite membranes. Sulfonated graphene oxide (sGO) was prepared from
      GO. Both sGO and GO were treated each with phenyl isocyanate and transformed into
      corresponding isGO and iGO in order to promote miscibility with Nafion. Then
      composite membranes were obtained, and the adaptability as a membrane for
      vanadium redox flow battery (VRFB) was investigated in terms of proton
      conductivity and vanadium permeability. Compared to a pristine Nafion, proton
      conductivities of both isGO/Nafion and iGO/Nafion membranes showed less
      temperature sensitivity. Both membranes also showed quite lower vanadium
      permeability at room temperature. Selectivity of the membrane was the highest for
      isGO/Nafion and the lowest for the pristine Nafion.

PMID- 25971011
TI  - Characterization of low temperature graphene synthesis in inductively coupled
      plasma chemical vapor deposition process with optical emission spectroscopy.
AB  - Low-temperature graphene was synthesized at 400 degrees C with inductively
      coupled plasma chemical vapor deposition (PECVD) process. The effects of plasma
      power and flow rate of various carbon containing precursors and hydrogen on
      graphene properties were investigated with optical emission spectroscopy (OES).
      Various radicals monitored by OES were correlated with graphene film properties
      such as sheet resistance, I(D)/I(G) ratio of Raman spectra and transparency. C2H2
      was used as a main precursor and the increase of plasma power enhanced intensity
      of carbon (C2) radical OES intensity in plasma, reduced sheet resistance and
      increased transparency of graphene films. The reduced flow rate of C2H2 decreased
      sheet resistance and increased transparency of graphene films in the range of
      this study. H2 addition was found to increase sheet resistance, transparency and
      attributed to reduction of graphene grain and etching graphene layers. OES
      analysis showed that C2 radicals contribute to graphite networking and sheet
      resistance reduction. TEM and AFM were applied to provide credible information
      that graphene had been successfully grown at low temperature.

PMID- 25971013
TI  - Anisotropic pattern transfer in ultrananocrystalline diamond films by inductively
      coupled plasma etching.
AB  - High density plasma etching of ultrananocrystalline diamond (UNCD) films
      wasperformed in O2 and O2/Ar inductively coupled plasma (ICP) discharges. The
      O2/Ar ICP discharges produced higher etch rates due to enhanced physical
      component of the etching, and a maximum etch rate of -280 nm/min was obtained in
      10 sccm O2/5 sccm Ar discharges. Very high etch selectivities up to -140:1 were
      obtained for the UNCD over Al mask layer. Anisotropic pattern transfer with a
      vertical sidewall profile was achieved in the 10 sccm O2/5 sccm Ar discharges at
      a relatively low source power (300 W) and a moderate rf chuck power (200 W).

PMID- 25971014
TI  - New analytical drain current model for the sub-linear region of output
      characteristics of graphene field-effect transistors in the low carrier density
      limit.
AB  - A new analytical drain current model for a quantitative description of output
      characteristics of graphene field-effect transistors (GFETs) in the sub-linear
      region is derived from a previously-developed diffusion-drift theory for GFETs.
      To simplify calculation, the diffusion-to-drift current ratio is assumed to be
      constant along the graphene channel, and a reasonable representative value of the
      ratio is used instead. In addition, the analytical modeling is conducted in the
      low-carrier-density limit where carrier velocity at the source end is lower than
      saturation velocity caused by optical phonon emission. This limit facilitates
      correct explanation of the peculiar behavior of output characteristics that has
      been attributed to an ambipolar property of graphene. For realistic simulation,
      extrinsic series resistances are considered, and carrier mobility degraded by
      vertical electric field is calculated from a modified classical formula. The
      output characteristics of GFETs in the sub-linear region can properly be
      reproduced by the new model, and good agreement between simulation results and
      several sets of experimental data taken from previous literatures is obtained in
      this region.

PMID- 25971015
TI  - Size-dependent resistive switching properties of the active region in nickel
      nitride-based crossbar array resistive random access memory.
AB  - The size-dependent resistive switching (RS) properties of the active region in a
      1 x 1 NiN-based crossbar array (CBA) resistive random access memory (ReRAM) are
      investigated in the range of 2 x 2 MUm2 to 8 x 8 MUm2. In the forming test, the
      forming voltage is reduced by decreasing the cell size of the active region.
      Compared to the 8 x 8 MUm2 CBA ReRAM, the forming voltage of the 2 x 2 MUm2 CBA
      ReRAM was reduced from 8 V to 6.2 V. In addition, V(SET/RESET) and the current
      for the reset operation are reduced in the current-voltage (I-V) results by
      reducing the cell size, while the current at a high-resistance state (HRS) is
      increased. As a result, the current ratio between the HRS and a low-resistance
      state (LRS) is reduced. On the other hand, the variation of V(SET) for I-V curves
      repetitively acquired 100 times is decreased by decreasing the cell size in the
      reliability test. Further, the current at the HRS for the 2 x 2 MUm2 CBA ReRAM is
      the most stable with the smallest current variation for 1000 s in the retention
      test. These results show that reducing the active region in the CBA ReRAM
      structure is effective for improving the reliability of ReRAM cells because it
      reduces the operating voltage and current as well as the variation of V(SET) and
      the current at the HRS.

PMID- 25971016
TI  - High conductivity and ultraviolet band transparency of single-walled carbon
      nanotube films bridged with gold nanoparticles.
AB  - We report the fabrication of single-walled carbon nanotube (SWNT) films bridged
      with gold nanoparticles (Au NPs) that exhibit high conductivity and transparency
      in the ultraviolet (UV) region. The film was obtained by annealing the Au films
      deposited onto quartz substrate by e-beam evaporation, followed by dip coating in
      SWNT-dispersed solution under different dipping cycles. The optical tranmittance
      spectrum of the film thus obtained shows a transmittance between 80.2 and 85% in
      the wavelength range of 350-600 nm. In addition, the SWNT film bridged with Au
      NPs shows an electrical conductivity of 1.72 mA at 5 V, which is about six-times
      higher than that of the SWNT film without Au NPs (0.29 mA). These results confirm
      that the Au NPs enhance the electrical conductivity of the SWNT network films,
      without compromising the optical transmittance.

PMID- 25971017
TI  - Effects of oxyfluorination on surface and mechanical properties of carbon fiber
      reinforced polarized-polypropylene matrix composites.
AB  - In this work, oxyfluorination treatments on carbon fiber surfaces were carried
      out to improve the interfacial adhesion between carbon fibers and polarized
      polypropylene (P-PP). The surface properties of oxyfluorinated carbon fibers were
      characterized using a single fiber contact angle, and X-ray photoelectron
      spectroscopy. The mechanical properties of the composites were calculated in
      terms of work of adhesion between fibers and matrices and also measured by a
      critical stress intensity factor (K(IC)). The K(IC) of oxyfluorinated carbon
      fibers-reinforced composites showed higher values than those of as-received
      carbon fibers-reinforced composites. The results showed that the adhesion
      strength between the carbon fibers and P-PP had significantly increased after the
      oxyfluorination treatments. As the theoretical and practical comparisons, OF-CF
      60s showed the best mechanical interfacial performance due to the good surface
      free energy. This indicates that oxyfluorination produced highly polar functional
      groups on the fiber surface, resulting in strong adhesion between carbon fibers
      and P-PP in this composite system.

PMID- 25971018
TI  - Ball-milling of graphite and muilti-wall carbon nanotubes.
AB  - The structural modification of graphite and multi-wall carbon nanotubes (MWCNTs)
      during ball-milling was examined. A comparison of structures after ball-milling
      was made between graphite and MWCNTs. The ball milling parameters were also
      examined: milling atmospheres, milling methods, milling mode and the addition of
      additive materials. In some experiments, hard materials such as alumina or silica
      were added to graphite and MWCNTs as additives to see whether graphite and MWCTs
      were shortened by ball-milling. The ball-milling of graphite and MWCNTs with
      liquid additives reduced the agglomeration of MWCNT and transformed graphite to
      graphenes. The ball-milling of MWCNTs under impact mode usually resulted in the
      formation of an amorphous phase, whereas that under friction mode induced the
      fattening of nanotubes. The results showed that a variety of carbon nanomaterials
      could be obtained by the proper controlling of ball milling. The structurally
      modified graphite and MWSNTs are expected to be utilized for energy storage
      application.

PMID- 25971019
TI  - Graphene treatment using a very low energy Ar+ ion beam for residue removal.
AB  - The effect of Ar+ ion energy on the removal of the polymethyl methacrylate (PMMA)
      residue remaining on the chemical vapor deposited (CVD) graphene surface without
      damaging the graphene surface was investigated. Stable and low energy Ar+ ion
      beams having a mono-energetic energy distribution with a peak energy of 7.5 eV or
      11.5 eV could be formed by using a two-grid magnetically enhanced ICP ion gun
      with and without the application of 25 Gauss axial magnetic field, respectively,
      while controlling the Ar gas flow rate. When the CVD graphene treatment was
      performed with the Ar+ ions having the ion energy peak at 7.5 eV (with the
      magnetic field) and 11.5 eV (without the magnetic field), the blue shift of Raman
      G peak from p-type doped to intrinsic graphene indicating the removal of residue
      on the graphene surface could be observed for both conditions, however, the
      graphene treated at 11.5 eV (without the magnetic field) showed the increase of
      the defect while that treated at 7.5 eV (with the magnetic field) showed no
      significant change of the defect. It is believed that, for the treatment of CVD
      graphene, possibly due to the low binding energy area such as grain boundaries
      and domains in the CVD graphene, low energy ions with less than the energy of 10
      eV is required not to damage the graphene surface, and a magnetically enhanced
      ICP ion gun which can provide stable and low energy Ar+ ions with a mono
      energetic ion energy distribution with a peak of 7.5 eV can be applicable to the
      residue removal on the graphene surface.

PMID- 25971020
TI  - Electrical and optical properties of poly(3,4-ethylenedioxythiophene) oxidized
      with poly(4-styrenesulfonate) and AuCl3-doped reduced graphene oxide/single
      walled carbon nanotube films for ultraviolet light-emitting diodes.
AB  - We report the effects of poly(3,4-ethylenedioxythiophene) oxidized with poly(4
      styrenesulfonate) ( PEDOT: PSS) and gold chloride (AuCl) co-doping on the
      electrical and optical properties of reduced graphene oxide (RGO)/single-walled
      carbon nanotube (SWNT) films fabricated by dipcoating methods. The RGO/SWNT films
      were doped with both AuCl3 dissolved in nitromethane and PEDOT: PSS hole
      injection layers by spin coating to improve their electrical properties by
      increasing the work function of the RGO/SWNT films, thereby reducing the Schottky
      barrier height between the RGO/SWNT and p-GaN films. As a result, we obtained a
      reduced sheet resistance of 851.9 Omega/Omega and a contact resistance of 1.97 x
      10(-1) Omega x cm2, together with a high transmittance of 84.1% at 380 nm. The
      contact resistance of these films should be further reduced to fully utilize the
      feature of the electrode scheme proposed in this work, but the current result
      suggests its potential use as a transparent conductive electrode for ultraviolet
      light-emitting diodes.

PMID- 25971021
TI  - Effect of Si3N4 thickness on the optical characterization of grapheme.
AB  - Optical detection of graphene on a specific substrate is important for the
      analysis of the physical or chemical properties of graphene. Si3N4, an oxygen
      free substrate with high dielectric constant, is a good candidate to replace
      SiO2. In this letter, we report the optimization of the Si3N4 thickness for
      efficient optical characterization by means of the contrast, enhancement factor
      (F), and the Raman spectra of the graphene obtained on the selected Si3N4/Si
      substrate. The contrast (visibility) and enhancement factors (F, Raman intensity)
      of the graphene/Si3N4/Si structure were calculated as a function of the Si3N4
      thickness and the wavelength of the excitation source. A suitable Si3N4 thickness
      generating high visibility and Raman intensities at the wavelength of the
      excitation source, 633 nm, was obtained.

PMID- 25971022
TI  - Microstructure and properties of silicon-incorporated DLC film fabricated using
      HMDS gas and RF-PECVD process.
AB  - The microstructure and characteristics of silicon-incorporated diamond-like
      carbon film, fabricated using a radio-frequency plasma-enhanced chemical vapor
      deposition process with hexamethyldisilane [(CH3)3,Si x Si(CH3)3:HMDS] gas as a
      silicon source, were investigated. Diamond-like carbon films with silicon
      compositions from 0 to 5 atomic percent were deposited onto ultra-fine grained
      AZ31 magnesium alloy substrate as buffer layers or multilayers. Si doping led not
      only to an increase in the bonding ratio (sp3/sp2), but improvements in hardness,
      critical adhesion, and corrosion resistance. Out of the investigated samples, the
      multi-deposited silicon diamond-like carbon thin film on magnesium substrate
      showed the best combination of adhesive, wear resistance, and corrosion
      resistance properties.

PMID- 25971023
TI  - Optical detection of argon gas flow based on vibration-induced change in
      photoluminescence of a semiconducting single-walled carbon nanotube bundle.
AB  - In this work, we demonstrate that Ar gas flow can be optically detected using
      mechanical vibration of a semiconducting single-walled carbon nanotube (SWCNT)
      bundle as a platform. A change in the photoluminescence (PL) intensity was
      induced by out-of-focusing of the SWCNT bundle of interest due to vibration
      caused by the introduced gas stream, for which a gas flow control system was
      installed in an optical microscope. The PL intensity was found to change
      systemically with the Ar flow rates in a range of relatively large flow rate
      intervals [0.70 to 3.0 standard cubic liters per minute (SLM) with 0.1-0.5 SLM
      intervals] with a noticeable hysteresis. It was, however, difficult to obtain a
      detectable PL change in a range of very small flow rate intervals (0.67 to 0.70
      SLM with a 0.01 SLM interval). The detailed results and underlying mechanism are
      discussed in detail.

PMID- 25971024
TI  - Hardness and wear resistance of carbon nanotube reinforced aluminum-copper matrix
      composites.
AB  - Recently, carbon nanotubes (CNTs) have been attracted to reinforcement of
      composite materials due to their extraordinary mechanical, thermal and electrical
      properties. Many researchers have attempted to develop CNT reinforced metal
      composites with various fabrication methods and have shown possibilities for
      structural and functional applications. Among them, CNT reinforced Al matrix
      composites have become very attractive due to their huge structural application
      in industry. In this study, CNT reinforced Al-Cu matrix composites with a
      microstructure of homogeneous dispersion of CNTs in the Al-Cu matrix are
      investigated. The CNT/Al-Cu composites are fabricated by mixing of CNT/Cu
      composite powders and Al powders by high energy ball mill process followed by hot
      extrusion process. The hardness and wear resistance of the CNT/Al-Cu composites
      are enhanced by 1.4 and 3 times, respectively, compared to those values for the
      Al-Cu matrix. This remarkable enhancement mainly originates from the homogeneous
      dispersion of CNTs in Al-Cu matrix and self-lubricant effect of CNTs.

PMID- 25971025
TI  - Electrically conductive epoxy nanocomposites with expanded graphite/carbon
      nanotube hybrid fillers prepared by direct hybridization.
AB  - Carbon nanotubes (CNTs) are generally used to promote the electrical conductivity
      of the polymer nanocomposites. However, in spite of their superior properties,
      CNT's high cost has limited their commercial application, so far. Thus, the
      development of hybrid carbon nanomaterials (CNMs) composed of CNTs and cheaper
      CNMs such as carbon fibers (CFs), expanded graphites (EGs), and graphene
      nanoplatelets (GNPs) is important in terms of reducing the cost of CNT-based
      fillers. In this study, we prepared EG/CNT hybrid fillers via direct CNT
      synthesis on the EG support using modified combustion method and thermal chemical
      vapor deposition (CVD) method, and investigated the electrical conductivity of
      the expoxy nanocomposite with EG/CNT hybrid fillers. The epoxy nanocomposites
      with EG/CNT hybrid fillers at 20 wt% filler loading showed 260% and 170%
      electrical conductivity enhancement in comparison with the EG and the simply
      mixed EG and CNT fillers, respectively. Our approach provides various
      applications including electromagnetic interference (EMI) shielding materials,
      thermal interface materials (TIMs), and reinforced nanocomposites.

PMID- 25971026
TI  - Aerosol approach for hollow spheres of a porous 3D carbon nanotube/CuO network
      and their anodic properties for lithium-ion battery.
AB  - Hollow spheres consisting of porous CNT/CuO nanocomposite networks were prepared
      by aerosol process and their enhanced anodic properties for lithium-ion battery
      were investigated. Hollow spheres of CNT/CuO nanocomposites showed a 3D network
      wherein the length of the electron path was quite short compared with the
      agglomerated CNT/CuO nanocomposites. From electrochemical measurements, CuO
      itself shows poor discharge capacity and cycling performance due to its low
      electronic conductivity. In the CNT/CuO nanocomposite, enhanced discharge
      capacity was observed and showed similar values regardless of the morphology.
      With the addition of CNTs to CuO, CNTs can form a network that acts as an
      electron path-way in the insulating CuO matrix, leading to increased electrical
      conductivity. The morphology of nanocomposite affected cycle stability. Hollow
      spheres of CNT/CuO nanocomposite showed better cycle stability than that of
      agglomerated CNT/CuO nanocomposite. The hollow sphere of a CNT/CuO nanocomposite
      comprising a 3D network of CNTs can be applied as a high capacity anode material
      in Li-ion batteries.

PMID- 25971027
TI  - TiO2 particles on a 3D network of single-walled nanotubes for NH3 gas sensors.
AB  - Ammonia (NH3) gas is one of the gases which causes damage to environment such as
      acidification and climate change. In this study, a gas sensor based on the three
      dimensional (3D) network of single-walled nanotubes (SWNTs) was fabricated for
      the detection of NH3 gas in dry air. The sensor showed enhanced performance due
      to the fast gas diffusion rate and weak interactions between the carbon nanotubes
      and the substrate. Metal oxide particles were introduced to enhance the
      performance of the gas sensor. Atomic layer deposition (ALD) was employed to
      deposit the metal oxide in the complex structure, and good control over thickness
      was achieved. The hybrid gas sensor consisting of the 3D network of SWNTs with
      anatase TiO2 particles showed stable, repeatable, and enhanced gas sensor
      performance. The phase of TiO2 particles was characterized by Raman and the
      morphology of the TiO2 particles on the 3D network of SWNTs was analyzed by
      transmission electron microscope.

PMID- 25971028
TI  - Dry spun 3D woven carbon nanotube anode electrode for Li-lon batteries.
AB  - Although carbon nanotubes (CNTs) have extraordinary mechanical, thermal, and
      electrical properties, application of CNTs remains limited due to their unique
      nano-sized tubular forms. CNT electrodes have relatively high sheet resistance,
      which does not meet the industrial requirements of various electrode materials.
      Thus, there are still challenges for improving the performance of CNTs in real
      applications, particularly in terms of satisfying industrial requirements. In
      this study, to utilize CNTs in bulk scale electrode applications, we developed a
      dry spinning technique. The dry spinning technique is a solid state fiber
      spinning technique that provides an adjustable aligned structure. The dry
      spinning approach also offers a facile and inexpensive fabrication process,
      factors which are favorable for industrial scalability for fabricating
      electrodes. We demonstrate a multilayer stacking process for enhancing the
      performance for Li-ion batteries. Multi-layer CNT textiles have low sheet
      resistance and a 3D woven structure provides high surface area. The fabricated 3D
      woven structured electrode delivers a higher reversible capacity of more than 400
      mA hr/g with high cycle stabilities.

PMID- 25971029
TI  - Molecular dynamics simulation of square graphene-nanoflake oscillator on graphene
      nanoribbon.
AB  - Graphene nanoflakes (GNFs) have been of interest for a building block in order to
      develop electromechanical devices on a nanometer scale. Here, we present the
      oscillation motions of a square GNF oscillator on graphene nanoribbon (GNR) in
      the retracting-motions by performing classical molecular dynamics simulations.
      The simulation results showed that the GNF oscillators can be considered as a
      building block for nanoelectromechanical systems such as carbon-nanotube (CNT)
      oscillators. The oscillation dynamics of the GNF oscillator were similar to those
      of the CNT oscillators. When the square GNF had an initial velocity as impulse
      dynamics, its oscillation motions on the GNR were achieved from its self
      retracting van der Waals force. For low initial velocity, its translational
      motions were dominant in its motions rather than its rotational motions. The
      kinetic energy damping ratio rapidly decreased as initial velocity increased and
      the kinetic energy for the translational motion of the GNF oscillator rapidly
      transferred into that for its rotational motion. The oscillation frequency of the
      GNF oscillator was dependent on its initial velocity.

PMID- 25971030
TI  - Carbon nanotube separation by electronic type using a single surfactant-based
      density-induced separation method.
AB  - We demonstrate a simple and efficient method for separating metallic from
      semiconducting single-walled carbon nanotubes (SWNTs) using density-gradient
      ultracentrifugation. Density differences between metallic and semiconducting
      SWNTs, which enable SWNT separation by electronic type, are created using a
      single surfactant, i.e., sodium dodecyl sulfate (SDS), rather than a complex
      mixtures of surfactant, as is used in current separation schemes. SDS strongly
      adsorbs onto the surface of metallic SWNTs over semiconducting SWNTs by the
      mirror-charge phenomenon. Therefore, metallic SWNT-SDS assemblies have relatively
      smaller buoyant densities than semiconducting SWNT-SDS assemblies; thus, the
      metallic assemblies are easily collected at the most buoyant top fractions,
      whereas the semiconducting assemblies are collected at the bottom fractions. We
      also demonstrate that this protocol is valid regardless of the SWNT production
      method; that is, SWNTs grown by high-pressure carbon monoxide conversion (HiPco)
      and the arc discharge method. Optical absorption shows that the heavy bottom
      fractions consist of highly pure semiconducting nanotubes, whereas the buoyant
      top fractions consist of highly pure metallic nanotubes. In addition, films made
      of the separated metallic SWNTs exhibit lower sheet resistances than unsorted
      SWNTs by 53% for arc discharged and 64% for HiPco SWNTs, as expected.

PMID- 25971031
TI  - Correlating defect density with growth time in continuous graphene films.
AB  - We report that graphene flakes and films which were synthesized by copper
      catalyzed atmospheric pressure chemical vapor deposition (APCVD) method using a
      mixture of Ar, H2, and CH4 gases. It was found that variations in the reaction
      parameters, such as reaction temperature, annealing time, and growth time,
      influenced the domain size of as-grown graphene. Besides, the reaction parameters
      influenced the number of layers, degree of defects and uniformity of the graphene
      films. The increase in growth temperature and annealing time tends to accelerate
      the graphene growth rate and increase the diffusion length, respectively, thereby
      increasing the average size of graphene domains. In addition, we confirmed that
      the number of pinholes reduced with increase in the growth time. Micro-Raman
      analysis of the as-grown graphene films confirmed that the continuous graphene
      monolayer film with low defects and high uniformity could be obtained with
      prolonged reaction time, under the appropriate annealing time and growth
      temperature.

PMID- 25971032
TI  - Growth of carbon nanowalls on metal-coated substrates via microwave plasma
      enhanced chemical vapor deposition.
AB  - In this study, we investigated the growth properties of carbon nanowalls (CNW)
      depending on the substrate types. We deposited metal films on Si substrates via
      RF magnetron sputtering with the use of four-inch W, Cu and Ni targets. A
      microwave plasma enhanced chemical vapor deposition (PECVD) system was used to
      grow CNWs on the metal-coated Si substrates using H2 and CH4 gases. The vertical
      and superficial conditions of the grown CNWs depending on the substrate types
      were characterized by field emission scanning electron microscopy (FE-SEM). Raman
      analysis was used to investigate the structural properties of the CNWs. Based on
      this experiment, it was found that the direct growth of CNW was possible on the
      metal layer with a thickness of more than 50 nm.

PMID- 25971033
TI  - Hierarchical porous carbon/MnO2 hybrids as supercapacitor electrodes.
AB  - Hybrid electrodes of hierarchical porous carbon (HPC) and manganese oxide (MnO2)
      were synthesized using a fast surface redox reaction of potassium permanganate
      under facile immersion methods. The HPC/MnO2 hybrids had a number of micropores
      and macropores and the MnO2 nanoparticles acted as a pseudocapacitive material.
      The synergistic effects of electric double-layer capacitor (EDLC)-induced
      capacitance and pseudocapacitance brought about a better electrochemical
      performance of the HPC/MnO2 hybrid electrodes compared to that obtained with a
      single component. The hybrids showed a specific capacitance of 228 F g(-1) and
      good cycle stability over 1000 cycles.

PMID- 25971034
TI  - Investigation of SF6 injection during cyclic C2H2/SF6 flow for the formation of
      geometrically controlled carbon coils.
AB  - Carbon coils could be synthesized using C2H2/H2 as source gases along with SF6 as
      an incorporated additive gas using a thermal chemical vapor deposition (CVD)
      system. To obtain geometrically controlled carbon coils, a cyclic process, namely
      the turning on and off of C2H2 or SF6 flow during the initial reaction stage, was
      carried out. According to the different reaction processes, different
      interruption/injection times of C2H2 or SF6 flow and different injection
      sequences of the gas flow were investigated while maintaining the identical
      overall injection time of C2H2 and/or SF6 flow. The formation of carbon
      microcoils (CMCs) is favored by the lowest interruption/injection time ratio of
      SF6 flow within one cycle. In addition, the injection of SF6 flow prior to the
      injection of C2H2 flow promotes the formation of CMCs. Based on these results we
      revealed the role of the SF6 flow injection for the enhanced formation of
      geometrically controlled CMCs. The etching of materials, thereby promoting an
      increase in the number of nucleation sites for the survived growth species to
      form CMCs, by the increased fluorine concentration, originating from the dominant
      SF6 influx, is understood to be the main cause for the exclusive CMCs formation.

PMID- 25971035
TI  - Fabrication of metal-coated carbon nanowalls synthesized by microwave plasma
      enhanced chemical vapor deposition.
AB  - In this study, the coating of synthesized carbon nanowalls (CNWs) with various
      metal layers (Ni, Cu, and W) was investigated. CNWs were synthesized by microwave
      plasma enhanced chemical vapor deposition (PECVD) with a methane (CH4) and
      hydrogen (H2) gas mixture on a p-type Si wafer, and then coated with metal films
      (Ni, Cu, and W) using an RF magnetron sputtering system with four-inch targets.
      Different sputtering times (5, 10, 20, and 30 min) were established to obtain
      different thicknesses of the metal layers with which the CNWs were coated. Field
      emission scanning electron microscopy (FE-SEM) was used to examine the cross
      sectional and planar conditions of the CNWs, and energy dispersive spectroscopy
      (EDS) was used to analyze the CNW elements. The FE-SEM analysis of the cross
      sectional and planar images confirmed that the metal layers were synthesized to a
      depth of 0.5 MUm from the surfaces of the CNWs, and to a greater depth at the
      ends of the CNWs, irrespective of the deposition time and the metal species. The
      resistivity of the as-deposited CNWs appeared as 4.18 x 10(-3) Omega cm; that of
      the metal-coated CNWs was slightly lower; and that of the Ni-coated CNWs was the
      lowest (1.74 x 10(-3) Omega cm). The mobility of the metal-coated CNWs was almost
      unchanged, and that of the as-deposited CNWs was 1.23 x 10(3) cm2 V(-1) s(-1).

PMID- 25971036
TI  - Hierarchically porous carbon/polyaniline hybrid for use in supercapacitors.
AB  - A hierarchically porous carbon (HPC)/polyaniline (PANI) hybrid electrode was
      prepared by the polymerization of PANI on the surface of the HPC via rapid-mixing
      polymerization. The surface morphologies and chemical composition of the HPC/PANI
      hybrid electrode were characterized using transmission electron microscopy and X
      ray photoelectron spectroscopy (XPS), respectively. The surface morphologies and
      XPS results for the HPC, PANI and HPC/PANI hybrids indicate that PANI is coated
      on the surface of HPC in the HPC/PANI hybrids which have two different nitrogen
      groups as a benzenoid amine (-NH-) peak and positively charged nitrogen (N+)
      peak. The electrochemical performances of the HPC/PANI hybrids were analyzed by
      performing cyclic voltammetry and galvanostatic charge-discharge tests. The
      HPC/PANI hybrids showed a better specific capacitance (222 F/g) than HPC (111
      F/g) because of effect of pseudocapacitor behavior. In addition, good cycle
      stabilities were maintained over 1000 cycles.

PMID- 25971037
TI  - Enhancement of hydrogen production from MeOH/H2O photo-splitting using micro
      /nano-structured SrSnO3/TiO2 composite catalysts.
AB  - Micro-/nano-structured SrSnO3/x wt.-% TiO2 composites (x = 10, 20, and 30) were
      designed using a mixed method, a typical hydrothermal and impregnation method, to
      enhance hydrogen production from MeOH/H2O photo-splitting. All the materials
      obtained exhibited a perovskite structure. Scanning electron microscopy revealed
      pure SrSnO3 to have a rod-like morphology with a square base, 0.7-1.5 MUm in
      size, and a height of approximately 2.0-3.0 MUm. Moreover, phenomena were
      observed in the rods similar to that of typical perovskite with a layered
      structure. TiO2 nanoparticles, < 100 nm in size, were observed in the SrSnO3/TiO2
      materials and the number of particles increased with increasing Ti concentration.
      The SrSnO3 material absorbed shorter band edges of less than 300 nm compared to
      that of pure TiO2, and the UV-visible absorption spectra were shifted to high
      wavelengths with the TiO2, loading. Hydrogen evolution from MeOH/H2O (1:1)
      photosplitting over the micro-/nano-structured SrSnO/TiO2 composite was enhanced
      compared to that over pure SrSnO3. In particular, 0.033 mmol of H2 gas was
      collected after 10 h under an 18 W-lamp with 365 nm radiation when 0.5 g of a
      SrSnO3/TiO2 20 wt.-% composite was used. Based on cyclic voltammetry and
      ultraviolet-visible spectroscopy, it was expected that the high photo activity
      resulted from the decrease in electron-hole recombination on the micro-/nano
      structured SrSnO3/TiO2 composite.

PMID- 25971038
TI  - Temperature-dependent electrical characteristics of c-Si and CIGS solar cells.
AB  - We characterized the electrical behavior of crystalline silicon (c-Si) and
      Cu(In(1-x)Ga(x))Se2 (CIGS) solar cells by current-voltage (I-V) and capacitance
      voltage (C-V) methods. We investigated the temperature-dependent carrier
      transport mechanism by determining the parameters of ideality factor (n) and
      activation energy (E(a)) deduced from I-V measurements. CLGS solar cells, as a
      function of temperature, showed drastic changes in n and E(a) in the space charge
      region (SCR) that forms near the ZnS/CIGS interface. Furthermore, by using a C-V
      measured substrate doping profiling method, we confirmed that the CIGS absorption
      layer had a graded band-gap structure from the end point of the SCR to the
      CIGS/Mo back contacts, while c-Si solar cells had a uniformly doped carrier
      concentration.

PMID- 25971039
TI  - Surface plasmon effect of Ag nanodots embedded in amorphous Si window layers
      deposited on Si solar cells.
AB  - We investigated solar cells containing temperature-dependent Ag nanodots embedded
      in an amorphous Si thin film layer by using hot-wire chemical vapor deposition in
      order to improve the properties of crystalline Si solar cells. An Ag thin film
      with a thickness of 10 nm was deposited by DC sputtering followed by annealing at
      various temperatures ranging from 250 to 850 degrees C for 15 min under N2 gas.
      As increasing the annealing temperature, the Ag nanodots were enlarged and the
      photoreflectances of the samples with Ag nanodots were lower than the reference
      samples in the spectral range of 200-600 nm, demonstrating the plasmon effect of
      Ag nanodots. The cell properties on photoluminescence spectra, quantum
      efficiency, and conversion efficiency were measured with the maximum values for
      the sample annealed at 450 degrees C, indicating that there exists an optimal
      size of the Ag nanodots about 15-35 nm to be effective on the enhancement of
      surface plasmon effect.

PMID- 25971040
TI  - Enhanced performance of polymer solar cells with a fluorocyanophenyl compound as
      an additive.
AB  - The efficiency of polymer solar cells (PSCs) with P3HT [poly(3-hexyl
      thiophene)]:PC61BM [[6,6]-phenyl C61-butyric acid methyl ester] blend film was
      improved by the incorporation of a fluorocyanophenyl compound, 3,4,5,6
      tetrafluorophthalonitrile (TFP), as an additive. When the amount of TFTadditive
      was 5 wt% based on the total amount of P3HT and PC61BM, the highest efficiency
      was achieved. The annealed PSC with 5 wt% TFP had a power conversion efficiency
      of 4.45% compared with that (3.57%) of the reference cell without the additive,
      which corresponds to an increase of about 18.7% in the efficiency due to an
      enhancement in the short circuit current (J(sc)). A seriese of measurements such
      as UV-visible absorption spectroscopy, X-ray measurements, atomic force
      microscopic images and incident photon to current conversion efficiency (IPCE)
      spectra revealed that the increased J(sc) in the PSC with P3HT:PC61BM:TFP blend
      film was due to an improvement in both exciton generation and charge transport
      efficiency, resulting from higher absorbance, larger crystal size and more
      effective phase separation.

PMID- 25971041
TI  - Formation of nanotextured surfaces on microtextured Si solar cells by metal
      assisted chemical etching process.
AB  - We investigated a nanotexturization process on the microtextured surface of
      monocrystalline Si solar cells which utilized a metal assisted chemical etching
      process. P-type Si solar cell wafers were used for nanotexturing followed by saw
      damage removal and a microtexturing process. As the nanotexturing time was
      increased, green and red-orange photoluminescence spectra at wavelengths of 506,
      507, and 637 nm were observed from the nanotextured cells, indicating that the
      quantum size effect caused the confinement of charge carriers in nanocrystalline
      silicon. The nanotextured cells showed a low photoreflectance of 4.5% in the
      visible spectral region of 400-600 nm. However, the reduced quantum efficiency
      from the nanotextured samples suggests that a shallow nanopore depth and density
      are required to prevent surface-related phenomena of charge recombination and
      surface current leakage.

PMID- 25971042
TI  - Heating effect on physical and electrochemical properties of nanofibrous
      polyacrylonitrile separator for lithium batteries.
AB  - Nanofibrous polyacrylonitrile (PAN) membranes as nonwoven separators were
      prepared by electrospinning followed by a thermal treatment to improve their
      physical properties. The effect of the thermal treatment on the physical and
      electrochemical properties of the PAN separators was investigated. With
      increasing heating time, the PAN nanofiber separators became denser with
      decreasing size of fully interconnected pores. The tensile strength and modulus
      of the nanofibrous PAN separators varied with the heating temperature and heating
      time. The maximum tensile strength and modulus were obtained at a heating
      temperature and heating time of 170 degrees C and 5 h, respectively. The cell
      assembled with the PAN separator prepared at 170 degrees C for 5 h exhibited high
      capacity retention and stable cycle performance, even at higher discharge current
      densities.

PMID- 25971043
TI  - Study of low resistivity and high work function ITO films prepared by oxygen flow
      rates and N2O plasma treatment for amorphous/crystalline silicon heterojunction
      solar cells.
AB  - Pulsed DC magnetron sputtered indium tin oxide (ITO) films deposited on glass
      substrates with lowest resistivity of 2.62 x 10(-4) Omega x cm and high
      transmittance of about 89% in the visible wavelength region. We report the
      enhancement of ITO work function (Phi(ITO)) by the variation of oxygen (O2) flow
      rate and N2O surface plasma treatment. The Phi(ITO) increased from 4.43 to 4.56
      eV with the increase in O2 flow rate from 0 to 4 sccm while surface treatment of
      N2O plasma further enhanced the ITO work function to 4.65 eV. The crystallinity
      of the ITO films improved with increasing O2 flow rate, as revealed by XRD
      analysis. The ITO work function was increased by the interfacial dipole resulting
      from the surface rich in O- ions and by the dipole moment formed at the ITO
      surface during N2O plasma treatment. The ITO films with high work functions can
      be used to modify the front barrier height in heterojunction with intrinsic thin
      layer (HIT) solar cells.

PMID- 25971044
TI  - Enhanced photovoltaic performance of novel TiO2 photoelectrode on TCO substrates
      for dye-sensitized solar cells.
AB  - In this study, we report synthesis and growth of rutile-anatase TiO2 thin film on
      fluorine-doped tin oxide (FTO) glass by a two-step hydrothermal method. The
      effects of additional treatments (i.e., TiCl4 post-treatment and seed layer
      formation were also studied. Photocurrent-voltage (I-V) measurement of rutile
      anatase TiO2 thin film was performed under 1.5 G light illumination. Photovoltaic
      performance was investigated by incident photon-to-electron conversion efficiency
      (IPCE), electrochemical impedance spectroscopy (EIS), intensity-modulated
      photocurrent/photovoltage spectroscopy (IMVS/IMPS) and open-circuit photovoltage
      decay (OCVD).

PMID- 25971045
TI  - Increased photovoltaic performance by the optimized TiClI4 and AlCl3 surface
      treatment in dye-sensitized solar cells.
AB  - The surface of TiO2 photoelectrodes coated on F-doped SnO2 (FTO) was modified by
      soaking it in a TiCl4:AlCl3 mixed aqueous solution with various molar ratios, and
      then calcining to produce the TiCl4:AlCl3-treated TiO2 photoelectrode (Ti:Al
      TiO2/FTO). The highest power conversion efficiency (PCE) was obtained from dye
      sensitized solar cells (DSSC) with Ti:Al(5:5)-TiO2/FTO, which was prepared from
      the mixed solution with the molar ratio of 5:5 (TiCi4:AlCl3). PCE of DSSC with
      Ti:Al (5:5)-TiO2/FTO was improved by ca. 19.6%, compared to that of the reference
      device with Ti:Al (10:0)-TiO2/FTO (i.e., TiO2-coated TiO2/FTO) due to an
      enhancement in both short-circuit photocurrent (J(sc)) and open-circuit voltage
      (V(oc)). A series of measurements such as UV-visible absorption, electrochemical
      impedance, open circuit voltage decay and dark current revealed that the increase
      in J(sc) was attributed to the improvement of electron collection efficiency by a
      prolonged electron lifetime, and the suppression of the charge recombination
      between injected electrons and I3(-) ions was found to increase the V(oc) value
      of the device with Ti:Al(5:5)-TiO2/FTO.

PMID- 25971046
TI  - Micro electro-mechanical system piezoelectric cantilever array for a broadband
      vibration energy harvester.
AB  - Limited energy sources of ubiquitous sensor networks (USNs) such as fuel cells
      and batteries have grave drawbacks such as the need for replacements and re
      charging owing to their short durability and environmental pollution. Energy
      harvesting which is converting environmental mechanical vibration into electrical
      energy has been researched with some piezoelectric materials and various
      cantilever designs to increase the efficiency of energy-harvesting devices. In
      this study, we focused on an energy-harvesting cantilever with a broadband
      vibration frequency. We fabricated a lead zirconate titanate (PZT) cantilever
      array with various Si proof masses on small beams (5.5 mm x 0.5 mm x 0.5 mm). We
      obtained broadband resonant frequencies ranging between 127 Hz and 136 Hz using a
      micro electro-mechanical system (MEMS) process. In order to obtain broadband
      resonant characteristics, the cantilever array was comprised of six cantilevers
      with different resonant frequencies. We obtained an output power of about 2.461
      MUW at an acceleration of 0.23 g and a resistance of 4 kOmega. The measured
      bandwidth of the resonant frequency was approximately 9 Hz (127-136 Hz), which is
      about six times wider than the bandwidth of a single cantilever.

PMID- 25971047
TI  - Influence of n-doped MUc-Si:H back surface field layer with micro growth in
      crystalline-amorphous silicon heterojunction solar cells.
AB  - The back surface field (BSF) plays an important role for the efficiency of the
      heterojunction intrinsic thin-film (HIT) solar cell. In this paper, the effect of
      thickness variation in n-type micro crystalline BSF layer was investigated by
      Raman and spectroscopy ellipsometry. As we increase the crystalline volume
      fraction (X(c)) from 6% to 59%, the open circuit voltage (V(oc)) increases from
      573 to 696 mV with increase in fill factor from 59% to 71%. However, we observed
      that V(oc) and FF are decreased over 59% X(c) of n-type MUc-Si:H BSF layer. It
      seems that higher X(c) micro layer include lots of defects. The quantum
      efficiency (QE) measurements were demonstrated on optimized thickness of n-doped
      micro BSF layer. In the long wavelengths region, the QE slightly increases with
      increasing the n-type MUc-Si:H BSF layer thickness from 10 to 40 nm because of
      BSF effect, whereas the QE decreases when n-type MUc-Si:H BSF layer thickness
      increases from 40 to 120 nm due to defects in the layer. The performance of
      heterojunction solar cell device was improved with the optimized thickness on n
      doped micro BSF layer the best photo voltage parameters of the device were found
      to be V(oc) of 696 mV, short-circuit current density of 36.09 mA/cm2 and
      efficiency of 18.06% at n-doped micro BSF layer thickness of 40 nm.

PMID- 25971048
TI  - Electrochemical properties of size-controllable polypyrrole/porous carbon for
      supercapacitor electrodes.
AB  - Polypyrrole (PPy)/activated carbon (AC) composite (SPPyC) with different PPy
      particle size are prepared without formation of chemical bonding between PPy and
      AC. The PPy particles were deposited on AC by miniemulsion polymerization and the
      size of PPy particles could be controlled by different surfactant amounts. The
      surface characteristics of SPPyC were characterized by Fourier transform infrared
      spectroscopy (FT-IR). The morphology of SPPyC was examined by scanning electron
      microscopy (SEM). The electrochemical performance of SPPyC was determined by
      cyclic voltammetry (CV) and galvanostatic charge/discharge characteristics in 6 M
      KOH electrolyte. The specific capacitances of SPPyC were higher than those of AC
      and the highest specific capacitance (125 F/g) of the S3PPyC was obtained at a
      current density of 0.5 A/g. This improved electrochemical performance of SPPyC
      was attributed to redox reaction by controlled PPy particle size.

PMID- 25971049
TI  - Electrical properties of dye-sensitized solar cells prepared by the binder-free
      TiO2 pastes.
AB  - Titania (TiO2) powder, which is material for photoelectrode in dye-sensitized
      solar cells (DSSCs), was fabricated by hydrothermal synthesis process at 230
      degrees C for 12 hours. The crystal structures of all the synthesized nano
      structured TiO2 films exhibited anatase phase. Binder-free pastes were prepared
      with the change of the amount of ammonia water from 2 MUl to 640 MUl in order to
      obtain the printable viscosity. It has been known that weak inter-particle bonds
      in slurry of flocculated particles make the slurry more viscous than slurry of
      dispersed particles. The increase of the amount of ammonia water for binder-free
      TiO2 pastes is attributed to the improvement of the viscosity of TiO2 paste and
      the power conversion efficiency of DSSCs using it. The viscosity of TiO2 pastes
      prepared at the ammonia water of 418 MUl exhibited the highest value about
      109,000 cP and also, was very transparent over 84%. As a result, the power
      conversion efficiency of DSSC prepared with the ammonia water of 418 MUl was
      about 3%.

PMID- 25971050
TI  - Deposition of zinc oxide photoelectrode using plasma enhanced chemical vapor
      deposition for dye-sensitized solar cells.
AB  - We investigated the characteristics of zinc oxide (ZnO) photoelectrodes grown by
      plasma enhanced chemical vapor deposition. ZnO has many advantages, such as high
      binding energy, breakdown strength, cohesion, hardness, and electron mobility. On
      the F-doped SnO2 (FTO) electrode, we deposited ZnO as a function of thickness,
      and we examined the thickness effect on the I-V, fill factor, open-circuit
      voltage, short-circuit current density, and especially the power conversion
      efficiency of the built in dye-sensitized solar cell. To study the thickness
      effect on the conduction and recombination of electrons in the ZnO electrode, we
      analyzed the alignment of grains, crystallinity, impedance, and cyclic I-V
      properties. The thickness of ZnO changed the electron diffusion length and
      recombination time. As a result, the maximum power conversion efficiency of 2.63%
      was obtained with a moderately thick (8.06 MUm) ZnO.

PMID- 25971051
TI  - Synthesis and characterization of CIS nanoparticle ink for low-cost thin film
      solar cells.
AB  - CuSe and CuInSe2 nanoparticles were synthesized through the aqueous solution
      process using NaBH4 solution as a solvent and subsequent heat-treatment. Not only
      the synthesized nanoparticles, CuSe and CuInSe2, but also spray-coated thin films
      prepared by using CuSe and CuInSe2 were characterized by XRD, SEM-EDS, TGA and UV
      Vis spectroscopy. CuSe nanoparticles with a plate-like shape, which were
      confirmed by XRD and SEM, were directly prepared by a reaction of a mixture of
      CuCl2 and Se in the aqueous solution of NaBH4 at room temperature. Cu-In-Se
      compounds were obtained through the reaction of CuCl2, InCl3, and Se in the
      aqueous solution of NaBH4, were consisted of the mixture of CuSe(x) and In
      hydroxides, and were transformed into CuInSe2 with a chalcopyrite structure by a
      heat-treatment at 300 degrees C.

PMID- 25971052
TI  - Characteristics of AZO electrode with high transmittance in near infrared range.
AB  - We studied Al2O3-doped ZnO (AZO) thin film as a transparent conducting layer for
      photovoltaic cell operated in wide range of solar spectrum. Effects of substrate
      temperature on the optical, structural, and electrical properties of thin AZO
      film were investigated. AZO films were deposited on glass substrates by RF
      magnetron sputtering system using a 2 wt.% Al2O3 doped target at different
      temperature conditions. The grown AZO films at low deposition temperatures ranged
      from 100 degrees C to 300 degrees C show relatively low resistivity, while the
      samples deposited at 400 degrees C or room temperature are with higher
      resistivity of -8 x 10(-4) Omega x cm. The measurement by atomic force microscopy
      reveals that all AZO films possess very smooth surface morphologies with RMS
      values below 1 nm regardless of substrate temperature. Optical transmittance of
      the AZO films increases from 81% to 95% as the substrate temperature increases.
      The AZO films deposited at 200 degrees C condition shows the optimum value of
      figure-of-merit of 43.7 x 10(-3) Omega(-1), showing the resistivity of 3.4 x 10(
      4) Omega x cm and the transmittance of 94%. Additionally, it is noted that the
      transmittance of the films at near infrared wavelength of 1250 nm exceeds 90%,
      demonstrating the feasibility as a transparent electrode for thin film solar cell
      with narrow band gap.

PMID- 25971053
TI  - Study on improved electrochemical properties of graphene nanosheet/nickel oxide
      composite as electrode materials.
AB  - Graphene nanosheets (GNS)/nickel oxide (NiO) composites were synthesized by a
      chemical method with a various amount of nickel precursor. For all composites,
      NiO nanoparticles were well decorated on the surface of graphene nanoplatelets.
      The structure and morphology analysis was performed by field emission scanning
      electron microscopy (FE-SEM), transmission electron microscopy (TEM) and X-ray
      diffraction (XRD). We confirmed that pure NiO particles are aggregated with each
      other and NiO particles dispersed on GNS prevent graphene from restacking in the
      composite. Electrochemical properties were also examined by cyclic voltammetry
      (CV). The optimum ratio of GNS to NiO was 1:20 (2 g of NiCl2 x 6H2O), showing the
      highest specific capacitance of 1034.7 Fg(-1) at 2 mV s(-1). This value was much
      higher than that of pure NiO and GNS, respectively. However, as the amount of
      nickel precursor increased, the specific capacitance displayed a decreasing
      tendency. It was probably due to the large agglomeration of NiO particles in high
      content of NiCI2 x 6H2O.

PMID- 25971054
TI  - Post-annealing of thin-film yttria stabilized zirconia electrolytes for anode
      supported low-temperature solid oxide fuel cells.
AB  - The effects of a post-annealing treatment on the performance of low-temperature
      solid oxide fuel cells (LT-SOFCs) were investigated. Nickel oxide-samarium doped
      ceria (NiO-SDC) anodes and yttria stabilized zirconia (YSZ) electrolytes were
      deposited on anodized aluminum oxide (AAO) membranes by RF sputtering and DC
      reactive sputtering, respectively. The half-cell of YSZ/NiO-SDC was then heat
      treated at 600 degrees C for 10 h, and a porous platinum (Pt) cathode was
      deposited on the annealed YSZ/NiO-SDC structure by DC magnetron sputtering.
      Electrochemical impedance spectroscopy (EIS) analysis revealed a significant
      decrease in the ohmic resistance and a slight increase in the cathodic impedance.
      Such a result may be attributed to the increased grain size and enhanced
      crystallinity of the YSZ electrolyte after the heat treatment. The maximum power
      density observed for the heat-treated cell was 35 mW/cm2 at 450 degrees C, more
      than three times higher than the 10 mW/cm2 value obtained for the as-deposited
      cell.

PMID- 25971055
TI  - Electrochemical properties of Si film electrodes grown on current collectors with
      CuO nanostructures for thin-film microbatteries.
AB  - Si film electrodes were deposited onto Cu foil current collectors fabricated with
      well-formed CuO nanostructures. The structural and electrochemical properties of
      the Cu foils oxidized for 1, 3, and 6 h and of the Si film electrodes were
      investigated using field-emission scanning electron microscopy, X-ray diffraction
      (XRD), and charge/discharge tests. The morphologies and XRD profiles suggested
      that the oxidized Cu foils consisted of a top CuO layer and a bottom Cu2O layer.
      The surface roughness of the Cu foils decreased with increasing oxidation time
      since the flower-like CuO nanostructures weakly adhered to the surface were
      easily detached by ultrasonic cleaning. The cycle performance of the Si film
      electrode with the rougher CuO layer rapidly deteriorated, whereas the flat Cu2O
      layer showing a relatively high electric conductivity induced the formation of a
      dense Si film and improved the electrochemical performance of the Si film
      electrode.

PMID- 25971056
TI  - Three-dimensional hierarchical Li4Ti5O12 nanoarchitecture by a simple
      hydrothermal method.
AB  - The spinel Li4Ti5O12 (LTO) is a promising candidate as a superior electrode
      material for energy storage devices due to the extremely small volume
      expansion/contraction during the charge/discharge processes of a battery. There
      are various synthetic approaches for the nanostructured LTO electrode: sol-gel,
      sonochemical, solution-combustion, hydrothermal methods, and others. Herein,
      three-dimensional (3D) high-density heterogeneous LTO architectures are
      fabricated by employing the TiO2 nanorods (NRs) branched SnO2 nanowire (NW)
      arrays as the template. The TiO2 NRs were effectively converted by the
      hydrothermal method into the LTO NRs that have a width of 40-nm and length of 100
      nm, which induce branch/backbone structured LTO-SnO2 composites. Interestingly,
      the 3D LTO architectures exhibit unique geometrical shapes because the NRs are
      surrounded by small nanoparticles. We also discuss how the temperature and
      solvent affect the LTO nanostructure formation in detail. These results suggest
      that using a template can provide a new method for designing and synthesizing
      various classes of 3D architecturing synthesis.

PMID- 25971057
TI  - Effects of solvents on the synthesis of CuInSe2 nanoparticles for thin film solar
      cells.
AB  - Chalcopyrite CuInSe2 (CIS) nanoparticles were synthesized in oleic acid, 1
      octadecene, oleyl amine and tetraethylene glycol at temperature above 200 degrees
      C. Depending on the solvent used and reaction temperature, the obtained
      nanoparticles had different shapes, sizes, chemical compositions, and crystal and
      thermal properties. CIS powders synthesized in oleic acid, 1-octadecene and oleyl
      amine above 200 degrees C exhibited chalcopyrite structure. On the other hand,
      powders prepared in tetraethylene glycol contained a mixture of CIS and CuSe
      compounds. The CIS powder obtained in oleyl amine had a high thermal stability
      over 500 degrees C. CIS thin films prepared from nanoparticles were heat-treated
      in order to observe changes in their property. After 10 min heat-treatment at 500
      degrees C, their crystal structure and chemical composition were slightly
      changed, and their band gap energies were ca. 1.01 eV except in the case of
      powders prepared in tetraethylene glycol.

PMID- 25971058
TI  - Enhanced performance of triboelectric nanogenerators integrated with ZnO
      nanowires.
AB  - We report a hybrid nanogenerator matrix integrated with ZnO nanowires (NWs) for
      the use of combined triboelectric and piezoelectric features, where the ZnO NWs
      are grown on bottom electrodes via a hydrothermal method. Along with structural
      properties analyzed by scanning electron microscopy, the hybrid nanogenerator
      displayed an output power density of 0.21 mW/cm2, which was higher than that of
      the triboelectric nanogenerator without NWs. Therefore, our approach can allow
      for the enhancement of electrical output, with a view toward the realization of
      functional and self-powered devices of high performance in portable electronics,
      such as power source and electric self-powered sensor systems.

PMID- 25971059
TI  - Preparation of 3D electrode microarrays of multi-walled carbon nanotubes/nafion
      nanocomposites for microfluidic biofuel cells.
AB  - Three-dimensional (3D) electrode microarrays with multi-walled carbon nanotubes
      (MWCNTs) reinforced Nafion nanocomposites were prepared for microfluidic biofuel
      cells. The oxidized MWCNTs (ox-MWCNTs) were prepared using chemical reactions
      with 60% nitric acid solution with pristine MWCNTs at 120 degrees C for 12 hrs
      with a nitrogen gas flow environment. Ox-MWCNTs in the range of 1 to 20 wt.%
      based on the Nafion polymer weight were reinforced to Nafion nanocomposites by
      solution casting. The micro-porous structure of the ox-MWCNTs reinforced Nafion
      nanocomposites was prepared by plasma etching for 5 to 20 min. The 10 wt.% ox
      MWCNTs reinforced Nafion nanocomposite produced stable micro-porous structures of
      3D electrodes by 10 min plasma etching. Micro-scale 3D structures of MWCNTs
      reinforced Nafion nanocomposites in a diameter range of 47 to 300 MUm were
      prepared by the micro-stencil assisted casting. To characterize the 3D electrode
      microarrays, the physical geometry and the reinforced MWCNT dispersion in the
      nanocomposite structure were examined using a scanning electron microscope (SEM)
      and an optical microscope. Thermal property measurements of the ox-MWCNTs
      reinforced Nafion nanocomposites with 10 min of plasma etching, and without
      plasma etching were made. Both showed stable thermal properties over 300 degrees
      C. The proposed 3D electrode microarray of MWCNT/Nafion nanocomposites with micro
      porous structures can be applied to miniaturized fuel cell devices.

PMID- 25971060
TI  - Passive approach for the improved dispersion of polyvinyl alcohol-based
      functionalized multi-walled carbon nanotubes/Nafion membranes for polymer
      electrolyte membrane fuel cells.
AB  - Multi-walled carbon nanotubes (MWCNTs) are regarded as ideal fillers for Nafion
      polymer electrolyte membranes (PEMs) for fuel cell applications. The highly
      aggregated properties of MWCNTs can be overcome by the successful cross-linking
      with polyvinyl alcohol (PVA) into the MWCNTs/Nafion membrane. In this study, a
      series of nanocomposite membranes were fabricated with the PVA-influenced
      functionalized MWCNTs reinforced into the Nafion polymer matrix by a solution
      casting method. Several different PVA contents were blended to f-MWCNTs/Nafion
      nanocomposite membranes followed by successful cross-linking by annealing. The
      surface morphologies and the inner structures of the resulting PVA-MWCNTs/Nafion
      nanocomposite membranes were then observed by optical microscopy and scanning
      electron microscopy (SEM) to investigate the dispersion of MWCNTs into the
      PVA/Nafion composite membranes. After that, the nanocomposite membranes were
      characterized by thermo-gravimetric analysis (TGA) to observe the thermal
      enhancement caused by effective cross-linking between the f-MWCNTs with the
      composite polymer matrixes. Improved water uptake with reduced methanol uptake
      revealed the successful fabrication of PVA-blended f-MWCNTs/Nafion membranes. In
      addition, the ion exchange capacity (IEC) was evaluated for PEM fuel cell (PEMFC)
      applications.

PMID- 25971061
TI  - Novel Ru(II) complex with 3-(2'-pyridyl)-1,8-naphthalimide derivative for dye
      sensitized solar cells.
AB  - A novel heteroleptic ruthenium(II) complex D1 with a pni (3-(2'-pyridyl)-1,8
      naphthalimide) derivative as a heteroleptic donor was designed and theoretical
      studies were performed of the molar absorptivity of D1 compared to that of the
      standard N749 dye and [Ru(dcbpy)2(ppy)] (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine,
      ppy = 2-phenylpyridine). Density functional theory (DFT) and time-dependent
      density functional theory (TD-DFT) calculations were used to gain an insight into
      the factors responsible for the photovoltaic properties of the dye sensitizer.
      The results showed that the absorption spectrum of the D1 dye with the pni
      derivative was red-shifted compared to N749 and [Ru(dcbpy)2(ppy)], particularly,
      in the region above 600 nm. The red-shift was attributed to the heteroleptic
      electron-donating ligands of the D1 dye. According to the molecular orbital
      analysis, the LUMO of the D1 dye mainly localized on tctpy (4,4',4"-tricarboxy-2
      2':6'.2"-terpyridine) moiety. HOMOs of the N749 were localized on the NCS moiety.
      However, HOMO and HOMO-2 of D1 were localized on the Ru-NCS moiety and the Ru-pni
      moiety, respectively. Owing to the additional HOMO-2, the D1 dye had a broad
      absorption spectrum and high photovoltaic efficiency compared to N749.

PMID- 25971062
TI  - Electrically exploded silicon/carbon nanocomposite as anode material for lithium
      ion batteries.
AB  - In this work, silicon (Si) containing carbon coated core-shell nanostructures
      were synthesized by electrical explosion of Si wires in ethanol solution followed
      by high energy mechanical milling (HEMM) process. Material characterization was
      carried-out using transmission electron microscopy (TEM), field-emission scanning
      electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), and X
      ray diffraction (XRD) analysis. HEMM led to very fine and amorphous Si particles
      in the presence of carbon and inactive Silicon-Carbide (SiC) matrix. These Si
      based nanocomposites, obtained through electrical explosion followed by HEMM
      (milled sample), exhibited enhanced electrochemical performance than unmilled
      nanocomposites, when evaluated as anode material for lithium-ion batteries
      (LIBs). On completion of (the) 1st cycle, milled and unmilled sample(s) showed
      specific discharge capacities around 825 mAh/g and 717 mAh/g, respectively.
      Interestingly, the coulombic efficiencies of milled and unmilled samples were
      98.5% and 97% after 60th cycle respectively. The enhanced electrochemical
      performance is attributed to fine and amorphous Si based nanocomposite obtained
      through HEMM process.

PMID- 25971063
TI  - Investigation of colloidal PbS quantum dot-based solar cells with near infrared
      emission.
AB  - Colloidal quantum dots (QD)-based solar cells with near infrared (NIR) emission
      have been investigated. Lead sulfide (PbS) QDs, which have narrow band-gap and
      maximize the absorption of NIR spectrum, were chosen as active materials for
      efficient solar cells. The inverted structure of indium tin oxide/titanium
      dioxide/PbS QDs/poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)/silver
      (ITO/TiO2/PbS QDs/ PEDOT: PSS/Ag) was applied for favorable electron and hole
      seperation from the PbS QD. Through the ligand exchange by 1,2-Ethanedithiol
      (EDT), the interparticle distance of the PbS QDs in thin film became closer and
      the performance of the PbS QD-based solar cells was improved. Our PbS QD-based
      inverted solar cells showed open circuit voltages (V(oc)) of 0.33 V, short
      circuit current density (J(sc)) of 10.89 mA/cm2, fill factor (FF) of 30%, and
      power conversion efficiency (PCE) of 1.11%. In our PbS QD-based multifunctional
      solar cell, the NIR light emission intensity was simply detected with photodiode
      system, which implies the potential of multi-functional diode device for various
      applications.

PMID- 25971064
TI  - Ionic conduction of lithium for (Li0.25La0.25)(1-x)Ca(0.5-x)TaO3 ceramics.
AB  - The ion transport properties of perovskite-type compounds (Li0.25La0.25)(1
      x)Ca(0.5x)TaO3, as lithium ionic conductors, are investigated (0 <= x <= 0.5).
      The compounds were synthesized by using a solid state reaction. X-ray diffraction
      (Li0.25La0.25)(1-x)Ca(0.5x)TaO3 indicates a structure that is transformed from
      cubic to tetragonal. The ion conductivity of lithium at room temperature
      decreases with an addition Ca2+ as a result of the decrease in lattice parameters
      resulting from the Ca2+ concentration.

PMID- 25971065
TI  - Synthesis of polycarbonate-r-polyethylene glycol copolymer for templated
      synthesis of mesoporous TiO2 films.
AB  - We synthesized a novel polycarbonate Z-r-polyethylene glycol (PCZ-r-PEG)
      copolymer by solution polycondensation. Successful synthesis of PCZ-r-PEG
      copolymer was confirmed by Fourier transform infrared spectroscopy (FTIR),
      nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), and
      transmission electron microscopy (TEM). PCZ-r-PEG copolymer was used as a
      structure-directing agent for fabrication of mesoporous thin film containing a
      titanium dioxide (TiO2) layer. To control the porosity of the resultant inorganic
      layer, the ratio of titanium(IV) isopropoxide (TTIP) to PCZ-r-PEG copolymer was
      varied. The structure and porosity of the resulting mesoporous films were
      characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM)
      analyses. Mesoporous TiO2 films fabricated on an F-doped tin oxide (FTO) surface
      were used as photoanodes for quasi-solid-state dye-sensitized solar cells
      (qssDSSCs). The highest efficiency achieved was 3.3% at 100 mW/cm2 for a film
      thickness of 750 nm, which is high considering the thickness of TiO2 film,
      indicating the importance of the structure-directing agent.

PMID- 25971066
TI  - Effect of nitrogen doping on the performance of dye-sensitized solar cells
      composed of mesoporous TiO2 photoelectrodes.
AB  - Nitrogen-doped mesoporous TiO2 (NMP TiO2) nanoparticles are synthesized using a
      soft triblock copolymer template by TiCl4 hydrolysis with ammonia water and
      applied to the photoelectrodes of dye-sensitized solar cells (DSSCs). The large
      surface area of a TiO2 mesoporous structure is favorable for dye uptake, and
      nitrogen doping of TiO2 is expected to increase the charge transport in the
      photoelectrode as well as the scattering of visible light. Structural
      characterizations for NMP TiO2 nanoparticles by XRD, XPS, BET, and BJH analyses
      revealed successful synthesis. However, the photovoltaic performances of the
      DSSCs prepared from NMP TiO2 were not improved, as had been expected: the photo
      conversion efficiency (eta) of DSSCs from undoped mesoporous TiO2 (MP TiO2) was
      4.69%, an improvement over the 4.15% with the application of P25 TiO2, but the
      efficiency of DSSCs from NMP TiO2 decreased to 3.2-3.6%. The measured amounts of
      adsorbed dye showed that nitrogen doping did not significantly affect dye
      adsorption. Therefore, it can be concluded that nitrogen doping increases
      isotropic charge transport in a TiO2 nanoparticle to promote charge recombination
      into an electrolyte, despite its advantages. The full benefits of nitrogen doping
      may be obtained through measures such as the deposition of a thin barrier layer
      of oxide onto the TiO2 surface to prevent charge recombination during charge
      transport in the TiO2 network.

PMID- 25971068
TI  - Hydrogen absorption and structural analysis of TiZrNiV quasicrystals.
AB  - Ti-based quasicrystals are known to store a high capacity of hydrogen exceeding
      the density of liquid hydrogen. Because TiZrNi quasicrystals contain a large
      number of tetrahedral sites formed with Ti and Zr atoms that are chemically
      favorable to hydrogen, these materials retain strong advantages for hydrogen
      storage applications in structurally and chemically. In fact, TiZrNi
      quasicrystals are known to absorb hydrogen maximum of the hydrogen to host metal
      ratio (H/M) value of near 2.0. The critical disadvantage, however, is that the
      equilibrium vapor pressure of hydrogen is very low (less than 1 Torr). To
      overcome this engineering drawback, we added a small amount of vanadium (V) in
      Ti(53-x)Zr27Ni20V(x), alloys (where x = 0 to 15) and rapidly quenched the molten
      ingots to form quasicrystals, and investigated the effects of V in terms of
      changes of structure, the H/M values, and an equilibrium vapor pressure of
      hydrogen. As the results, an equilibrium vapor pressure significantly increased
      from 0.84 to 2.16 Torr while the maximum H/M value decreased from 1.32 to 1.11 as
      increasing x = 0 to 8. After hydrogenation, the main peaks shifted evenly to the
      lower angle of 20 in X-ray diffraction patterns with uniform expansion of the
      quasilattice constants which demonstrates that hydrogen atoms homogeneously
      diffused into the samples. A Laves phase starts to form at x = 13 and the samples
      completely transformed to the phase at x = 15 suggesting the similarity between
      the quasicrystal and the Laves phase.

PMID- 25971067
TI  - Surface modification of polypropylene separators in lithium-ion batteries using
      inductively coupled plasma treatment.
AB  - We describe herein an improvement in the surface wettability of plasma-treated
      separators for use in lithium-ion batteries. We treated the separators with an
      O2/Ar inductively coupled plasma to increase their surface energy. The plasma
      treatment on the separator and plasma diagnostic experiments were performed in an
      inductively coupled plasma (ICP) reactor. The fraction of Ar in the O2/Ar plasma
      was changed from 0% to 100%. The plasma diagnostics were performed using optical
      emission spectroscopy and a double Langmuir probe. To confirm the morphological
      change of the separator membrane by the plasma treatment, we used the scanning
      electron microscopy. The surface energy measurements were performed using the
      drop method. We found that the plasma treatment transformed the separator from a
      hydrophobic membrane to a hydrophilic one, thereby achieving high separator
      wettability. After the treatment of the separators with O2/Ar plasma, the
      batteries exhibited better cycle performance and rate capacity than those
      employing the untreated ones.

PMID- 25971069
TI  - Optimized performance of quasi-solid-state DSSC with PEO-bismaleimide polymer
      blend electrolytes filled with a novel procedure.
AB  - Dye-sensitized solar cell (DSSC) is an attractive renewable energy technology
      currently under intense investigation. Electrolyte plays an important role in the
      photovoltaic performance of the DSSCs and many efforts have been contributed to
      study different kinds of electrolytes with various characteristics such as liquid
      electrolytes, polymer electrolytes and so on. In this study, DSSC is developed by
      using quasi-solid electrolyte and a novel procedure is adopted for filling this
      electrolyte. The quasi-solid-state electrolyte was prepared by mixing Poly
      ethylene oxide (PEO) and bismaleimide together and constitution was taken as PEO
      (15 wt%) at various bismaleimide concentrations (1, 3, 5 wt%). The novel
      procedure of filling electrolyte consists of three major steps (first step:
      filling liquid electrolyte, second step: vaporization of liquid electrolyte,
      third step: refilling quasi-solid-state electrolyte). The electrochemical and
      photovoltaic performances of DSSCs with these electrolytes were also
      investigated. The electrochemical impedance spectroscopy (EIS) indicated that
      TiO2/Dye/electrolyte impedance is reduced and electron lifetime is increased, and
      consequently efficiency of cell has been improved after using this novel
      procedure. The photovoltaic power conversion efficiency of 6.39% has been
      achieved under AM 1.5 simulated sunlight (100 W/cm2) through this novel procedure
      and by using specified blend of polymers.

PMID- 25971070
TI  - Hydrophilicity-controlled ordered mesoporous carbon for lithium-sulfur batteries.
AB  - Ordered mesoporous carbon (OMC) materials were synthesized from a mesoporous
      silica KIT-6 (3-D cubic la3d meso-structure) as the hard-template via a nano
      replication method. Hydrophilic and hydrophobic OMC materials were prepared using
      different carbon precursors including sucrose (suc-OMC) and phenanthrene (phe
      OMC) at different carbonization temperatures of 700 degrees C and 1100 degrees C,
      respectively. The OMC materials thus obtained exhibit high surface areas, uniform
      mesopore sizes and highly ordered meso-structure. To investigate the
      hydrophilicity effect of OMC materials on the performance of lithium-sulfur
      battery, we prepared the samples having different ratios of the suc-OMC to phe
      OMC, which were 100:0, 75:25, 50:50, 25:75 and 0:100. As a result, the mixed OMC
      materials (with ratios of 75:25, 50:50 and 25:75) exhibited better cycle
      performances, compared to those of the suc-OMC and phe-OMC.

PMID- 25971071
TI  - A novel method to make boron-doped microcrystalline silicon thin films with
      optimal crystalline volume fraction for thin films solar cell applications.
AB  - Highly conducting boron-doped microcrystalline silicon (p-type MUc-Si:H) thin
      films have been prepared by radio frequency plasma-enhanced chemical-vapor
      deposition (RF-PECVD). In this work, the effects of hydrogen dilution, doping
      ratio, plasma power, deposition pressure and substrate temperature on the growth
      and the properties of boron-doped microcrystalline silicon (p-type MUc-Si:H) thin
      films are investigated. The electrical, chemical and structural properties are
      improved with increasing crystallite, which depends on the plasma conditions. For
      various plasma parameters, the crystalline volume fraction (X(c)), dark
      conductivity (sigma(d)), activation energy (E(a)), hydrogen content (C(H)),
      surface roughness (S(r)), and micro void fraction (R*) were measured, and they
      were 0-72%, 4.17-10(-4) S/cm-1.1 S/cm, 0.041-0.113 eV, 3.8-11.5 at.%, 3.2 nm-12.2
      nm, and 0.47-0.80, respectively. The film with R* of 0.47 and C(H) of about 5
      at.% belonged to a region of low disorder, and acted as a good passivation layer.

PMID- 25971072
TI  - Carbon-coated carbon black as stable electrocatalyst support for polymer
      electrolyte membrane fuel cells.
AB  - The surface of commercial carbon black was modified by pyrolysis of acetonitrile
      in attempt to obtain the graphitic carbon coating layer. It was confirmed that
      the surface of carbon black was partially graphitized, having 0.23 of
      graphitization index and 1.87 nm of mean stack height. From the electrochemical
      oxidation test of carbon, the carbon-coated carbon black showed higher corrosion
      resistance than the untreated carbon black although the core of the carbon black
      support still remained untreated. When it was applied to the support for platinum
      electrocatalyst, the enhanced stability was observed. From those corrosion tests
      as well as XPS results, it can be suggested that the partially crystalline
      graphitic carbon surface facilitates the relatively more reduced surface of
      platinum.

PMID- 25971073
TI  - Interface modification in solar cell contact electrode using pre-cleaning
      treatment chemistries.
AB  - Promoting and employing photovoltaic power as an alternative energy source, the
      solar cell industry has made rapid strides. However, improving the efficiency of
      these solar cells using low-cost fabrication processes is still needed. The
      interface between the Si surface and the electrode plays a very important role in
      the process of electrode formation of the solar cell. In this study, the
      electrode interface underwent four different pre-treatments in order to enhance
      the efficiency of Si-based solar cells. We analyzed the adhesion properties at
      the interface between the Si wafer and the electrode and conducted an analysis of
      the variation in contact resistance between the two contact surfaces. To reduce
      the cost of the entire experiment, we replaced the existing Ag screen printing
      based electrode fabrication method with a low-temperature, low-cost Ni/Cu
      electroless plating method. The test cells exhibited improved adhesion and
      therefore improved efficiency as compared to cells treated with the currently
      used diluted HF.

PMID- 25971074
TI  - Comparison of photovoltaic properties of TiO2 electrodes prepared with
      nanoparticles and nanorods.
AB  - In this report, single crystalline rutile TiO2 nanoparticles and nanorods were
      synthesized via the hydrothermal method using titanium tetra-isopropoxide as a
      precursor then, these were coated on top of a fluorine-doped tin oxide (FTO)
      substrate by using a doctor blade and direct deposition, respectively.
      Consequently, TiO2 nanorods-based dye-sensitized solar cells (DSSC) exhibit a
      J(sc) of 3.37 mA/cm2, a V(oc) of 0.82 V and fill factor of 60.1% with an overall
      conversion efficiency of 1.66%. This result shows an increase of around 38% for
      current density and 35% for conversion efficiency. Also, with respect to the
      impedance data, TiO2 nanorods-based DSSCs had smaller semicircles than did the
      nanoparticles-based DSSCs. These results demonstrate that the nanorod structure
      can have fast electron transport and reduced charge recombination.

PMID- 25971075
TI  - Surface degradation mechanism during the fluorine-based plasma etching of a low-k
      material for nanoscale semiconductors.
AB  - The degradation of a low-k material surface during the exposure to plasma etching
      is one of the most serious problems to be solved for the realization of high
      speed semiconductor devices. In this study, the factors causing the degradation
      of a low-k material surface during the etching using fluorine-based plasma
      etching have been investigated by using XPS. As the plasma factors, active
      radicals, bombardment energy, and charge of the ions were considered and, as the
      low-k material, methyl silsesquioxane (MSQ) has been used. The XPS results showed
      that the ion bombardment during the plasma etching of MSQ affects the breaking of
      MSQ bone structure by changing the Si-O bonds and Si-C bonds to Si-F mostly,
      while fluorine-based radicals in the plasma mostly affect the change of Si-CH3
      bonds to Si-CH(x)F(y). By removing the charge of the ions during the bombardment,
      the MSQ properties were further improved. When F intensity which is related to
      the damage of the MSQ surface is estimated, the bombardment energy, reactive
      radical density, and charge of the ions were responsible for -18%, -53%, -19% of
      the F intensity in the MSQ. Therefore, by using the neutral beam etching instead
      of a conventional ICP etching, the degradation on the MSQ surface estimated by
      the F intensity remaining on the MSQ surface could be decreased to 10%.

PMID- 25971076
TI  - Fabrication and electrical characterization of graphene formed chemically on
      nickel nano electro mechanical system (NEMS) switch.
AB  - In this work, we successfully fabricated a reliable nano-electro-mechanical
      system (NEMS) switch with graphene formed chemically on pre-patterned nickel (Ni)
      film movable beam. Its electrical characteristics were investigated in terms of
      current-voltage (I-V) and repetitive switching (on/off) properties. The graphene
      in the movable beam was selectively formed chemically only on the patterned Ni
      film. Graphene material may help overcome the stiction and reliability problems
      in nano-electro-mechanical devices. A study on graphene cantilever already has
      been reported by using only single or multi-layer of transferred graphene.
      However, the graphene selectively grown on Ni film has not been reported for NEMS
      switch. The graphene grown on Ni film by chemical vapor deposition method (CVD)
      were characterized by Raman spectroscopy. The fabricated lateral NEMS switch has
      w/l/t = 500 nm/20 MUm/150 nm as a Ni dimension and an air-gap of -300 nm in
      lateral direction. The fabricated graphene movable beam formed chemically on Ni
      film shows reduced pull-in voltage and improved endurance (extended repetitive
      switching operations).

PMID- 25971077
TI  - Fabrication of nanometer electrodes by electro migration on an embedded metal
      pattern.
AB  - Electrodes with several tens nanometer gap are very important parts in the nano
      devices such as SETs (Single Electron Transistor), and quantum dots. However,
      fabricating nanometer electrode with the EBL (Electron Beam Lithography) process
      is too costly and time consuming to be commercially feasible. To overcome these
      disadvantages and to enable mass production, nano imprint lithography is applied
      to a master fabrication technique via EBL. In this paper, several tens nanometer
      gap electrodes are fabricated by EBL in order to characterize SET. The embedded
      metal pattern is made by the NIL (Nanoimprint Lithography) process, which is
      suggested for mass production. In order to fabricate without chemical process,
      the embedded metal process was executed with nanoimprint lithography. And the
      nanometer gap was made by electro migration process on flexible film substrate.
      That is, the electro migration process was executed on the embedded metal pattern
      to fabricate the nano gapped electrodes.

PMID- 25971078
TI  - Mechanical and fatigue characteristics of Ti-6Al-4V extra low interstitial and
      solution-treated and annealed alloys after ultrasonic nanocrystal surface
      modification treatment.
AB  - This study investigates the influence of ultrasonic nanocrystal surface
      modification (UNSM), a novel surface treatment technology, on the mechanical
      characteristics and rotary bending fatigue performance of solution-treated and
      annealed (STA) Ti-6Al-4V and Ti-6AI-4V extra low interstitial (ELI) alloys.
      Various techniques have been developed to use surface modification in order to
      improve fatigue performance of machine parts. The UNSM treatment emerges due to
      its ability to induce a distinctive combination of modifications in the top
      surface and the subsurface of the material. The mechanical properties are
      acquired and compared for UNSM-treated and untreated specimens. Fatigue data is
      acquired and compared for UNSM-treated and untreated specimens of Ti-6Al-4V ELI
      alloy by subjecting specimens to rotary-bending fatigue tests. Fracture analysis
      of failed specimens is performed. The improvement in the fatigue performance is
      observed for UNSM treated specimens. This improvement is attributed mainly to the
      UNSM-induced combination of following modifications: compressive residual stress,
      micro-hardness, and nanograin in the subsurface of the material.

PMID- 25971079
TI  - Impacts of recessed gate and fluoride-based plasma treatment approaches toward
      normally-off AlGaN/GaN HEMT.
AB  - We report two approaches to fabricating high performance normally-off AIGaN/GaN
      high-electron mobility transistors (HEMTs). The fabrication techniques employed
      were based on recessed-metal-insulator-semiconductor (MIS) gate and recessed
      fluoride-based plasma treatment. They were selectively applied to the area under
      the gate electrode to deplete the two-dimensional electron gas (2-DEG) density.
      We found that the recessed gate structure was effective in shifting the threshold
      voltage by controlling the etching depth of gate region to reduce the AIGaN layer
      thickness to less than 8 nm. Likewise, the CF4 plasma treatment effectively
      incorporated negatively charged fluorine ions into the thin AIGaN barrier so that
      the threshold voltage shifted to higher positive values. In addition to the
      increased threshold voltage, experimental results showed a maximum drain current
      and a maximum transconductance of 315 mA/mm and 100 mS/mm, respectively, for the
      recessed-MIS gate HEMT, and 340 mA/mm and 330 mS/mm, respectively, for the
      fluoride-based plasma treated HEMT.

PMID- 25971080
TI  - Effect of Al2O3 insulator thickness on the structural integrity of amorphous
      indium-gallium-zinc-oxide based thin film transistors.
AB  - The current transparent oxide semiconductors (TOSs) technology provides
      flexibility and high performance. In this study, multi-stack nano-layers of TOSs
      were designed for three-dimensional analysis of amorphous indium-gallium-zinc
      oxide (a-IGZO) based thin film transistors (TFTs). In particular, the effects of
      torsional and compressive stresses on the nano-sized active layers such as the a
      IGZO layer were investigated. Numerical simulations were carried out to
      investigate the structural integrity of a-IGZO based TFTs with three different
      thicknesses of the aluminum oxide (Al2O3) insulator (delta = 10, 20, and 30 nm),
      respectively, using a commercial code, COMSOL Multiphysics. The results are
      graphically depicted for operating conditions.

PMID- 25971082
TI  - Impact of process parameters on pattern formation of the self-aligned multiple
      patterning process.
AB  - Double patterning (DP) and multiple patterning (MP) are techniques employed to
      extend the useful life of optical lithography through higher density chip
      transistors. The self-aligned double patterning (SADP) and the self-aligned
      multiple patterning (SAMP) are promising technologies that can be expanded to 22
      nm and 1 x nm patterns for the dynamic random access memory (DRAM) and NAND flash
      memory devices. It is important to understand how the final pattern is related to
      each SADP or SAMP step to optimize process parameters and develop those
      processes. In this paper, the SADP and the SAMP model the optical lithography
      process and the spacer-aligned process to reduce those complexites and optimize
      those critical dimension uniformities (CDUs). For the spacer-aligned process,
      deposition and etching were modeled using a ray-trace algorithm and a level-set
      method. For the SADP and the SAMP, simulation results similar to the experimental
      results allow the prediction of self-aligned patterns and the pattern effects of
      process parameters.

PMID- 25971081
TI  - Effect of atmospheric-pressure plasma treatment on the adhesion characteristics
      of screen-printed Ag nanoparticles on polyimide.
AB  - We investigated the adhesion characteristics of screen-printed silver (Ag) tracks
      on polyimide (PI) treated by atmospheric-pressure plasma (APP). Oxygen plasma was
      applied to the PI surface, and the APP-treated surface was exposed to air for
      various periods of time in order to evaluate the sustainability of the APP
      treatment. The adhesion of the Ag/PI interface was measured using a roll-type 90
      degrees peel test. The peel strength was dramatically increased by the APP
      treatment, but the strength decreased by around 62.7% when the APP-treated PI
      surface was exposed to air for 2 h. The peeled PI surface showed ductile fracture
      immediately after the APP treatment; however, after 2 h of exposure to air, the
      fracture behavior returned what was observed before the APP treatment. To analyze
      the deterioration of adhesion, the interface between the printed Ag track and the
      APP-treated PI was investigated physically and chemically. The surface morphology
      became rougher after the APP treatment, but the roughness slightly decreased
      after being exposed to air for 2 h. X-ray photoelectron spectroscopy (XPS) was
      used to investigate the chemical bonding of the printed Ag and the PI interface.
      XPS analyses show that the concentration of oxygen-containing groups decreased as
      the exposure time to air increased.

PMID- 25971083
TI  - Resistive switching characteristics of ZnO nanowires.
AB  - Binary transition metal oxides such as ZnO, TiO2, and MnO; and their various
      structures such as thin film, nanowire, and nanoparticle assembly; have been
      widely investigated for use in insulators in resistive random access memory
      (ReRAM), considered a next-generation nonvolatile memory device. Among the
      various driving mechanisms of resistive switching in insulating materials, the
      conductive filament model is one of the most widely accepted. Studies on
      spatially confined structures such as one-dimensional nanostructures and zero
      dimensional nanoparticles to reveal the detailed filament constructing mechanism
      are warranted because low-dimensional nanostructures can provide more localized
      properties with a narrow dispersion of operational parameter values compared with
      thin-film structures. We investigated the resistive switching characteristics of
      ZnO nanowire (NW) structures. The NWs were grown on an Au/Ti/SiO2/Si substrate
      via the hydrothermal method. The empty space between the top and bottom
      electrodes was filled with a photoresist to prevent direct connection between the
      electrodes. The top electrode (Cr) and bottom electrode (Au), both with a
      thickness of -100 nm, were deposited by DC sputtering. The current-voltage (I-V)
      measurements were performed using a semiconductor characterization system.
      Additionally, the local current image and the point I-V characteristics for each
      NW were examined by replacing the top electrode with a conducting atomic force
      microscope tip. The Au-ZnO NW-Cr devices exhibited bipolar resistive switching
      behavior.

PMID- 25971084
TI  - Application of a multi-channel microfluidic chip on the simultaneous detection of
      DNAs by using microbead-quantum dots.
AB  - Several researches have shown that cancer is caused by genetic mutations
      especially in genes involved in cell growth and regulation. Ras family members
      are frequently found in their mutated, oncogenic forms in human tumors. Mutant
      RAS proteins are constitutively active, owing to reduce intrinsic GTPase activity
      and insensitivity to GTPase-activating protein (GAPs). In total, activating
      mutations in the RAS genes occur in approximately 20% of all human cancers,
      mainly in codon 12, 13 or 61. Activating mutations in the NRAS gene not only
      result in the reduction of intrinsic GTPase activity but also in the induction of
      resistance against molecules inducing such activity. In this paper, we reported a
      rapid, simple and portable method for detecting the mutant types of NRAS genes
      codon 12 and 61 simultaneously by using bead-quantum dots (QDs) based multi
      channel microfluidic chip. Probe DNAs are conjugated to bead-QDs and packed in
      the pillars of channels in the microfluidic chip. After injection of target DNAs
      and intercalating dyes, the fluorescence quenching of QDs by intercalating dye
      was observed due to FRET phenomena. The platform can be effortlessly applied in
      other biological and clinical areas.

PMID- 25971085
TI  - Pulse-biased etching of Si3N4-layer in capacitively-coupled plasmas for nano
      scale patterning of multi-level resist structures.
AB  - Pulse-biased plasma etching of various dielectric layers is investigated for
      patterning nano-scale, multi-level resist (MLR) structures composed of multiple
      layers via dual-frequency, capacitively-coupled plasmas (CCPs). We compare the
      effects of pulse and continuous-wave (CW) biasing on the etch characteristics of
      a Si3N4 layer in CF4/CH2F2/O2/Aretch chemistries using a dual-frequency,
      superimposed CCP system. Pulse-biasing conditions using a low-frequency power
      source of 2 MHz were varied by controlling duty ratio, period time, power, and
      the gas flow ratio in the plasmas generated by the 27.12 MHz high-frequency power
      source. Application of pulse-biased plasma etching significantly affected the
      surface chemistry of the etched Si3N4 surfaces, and thus modified the etching
      characteristics of the Si3N4 layer. Pulse-biased etching was successfully applied
      to patterning of the nano-scale line and space pattern of Si3N4 in the MLR
      structure of KrF photoresist/bottom anti-reflected coating/SiO2/amorphous carbon
      layer/Si3N4. Pulse-biased etching is useful for tuning the patterning of nano
      scale dielectric hard-mask layers in MLR structures.

PMID- 25971086
TI  - Low-ppm-Level colorimetric acid detection using gold nanoparticles with electro
      steric stabilization.
AB  - Electro-sterically stabilized gold suspensions were employed in a colorimetric
      system for the detection of strong acid in water. Using oleyamine and oleic acid
      as steric stabilizer in 1,2-dichlorobenzene, hydrophobic gold nanoparticles were
      first synthesized by a reduction reaction of gold salts and were then transferred
      into water with a cationic surfactant. When the hydrochlo- ric acid solution
      higher than critical concentration was injected, particles were quickly
      aggregated and precipitated, creating a clear solution from the colored
      suspension. The particles were stable against chemical etching by corrosive ion
      such as chloride. Critical concentration was dependent of the size and
      concentration of the particles. The minimum concentration of dramatic color
      change was at 5 ppm level of hydrochloric acid, in which the largest colloidal
      gold nanoparticles (54 nm) were used. Furthermore, because of their steric
      repulsive soft layer on particles, particles could be reused for further
      detection experiments after regeneration by the simple pH-neutralization and
      washing process.

PMID- 25971087
TI  - Alumina surface recovery for the particle reduction.
AB  - The method for the alumina surface regeneration and the particle reduction in an
      inductively coupled plasma are described. Due to the chemical reaction between
      the alumina surface and the oxygen gas in high temperature plasma, the by product
      AI(OH)3 is formed. Then, it fell out to the wafer as the particle. Since the
      particles mainly generated from the alumina surface, the seasoning process was
      progressed after the photoresist (PR) strip process. As the results, the
      byproduct of the alumina surface changed from Al(OH)3 to Al2O3 after the
      seasoning process. Then, total number of the particles on the wafer was
      considerably reduced. For the surface analysis, X-ray Photoelectron Spectroscopy
      (XPS) and FT-IR were applied to comparing the status of the alumina surface
      before and after the seasoning process.

PMID- 25971088
TI  - Structuring poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) towards
      enhancing hole collection efficiency.
AB  - To date, organic photovoltaic devices (OPVs) have obtained relatively low power
      conversion efficiency, mostly because of the low charge carrier mobility of the
      polymers to be used. This limits the optimal film thickness for efficient
      absorption of the solar spectrum. The capability of efficient charge carrier
      collections is a main factor for utilizing thick OPVs, consequently enhancing the
      power conversion efficiency. In this report, we demonstrate a facile approach for
      enhancing the hole carrier collection by possibly shortening the hole collection
      path via structuring poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (
      PEDOT: PSS), which is widely used as a hole collecting intermediate layer in
      OPVs. For structuring the PEDOT: PSS, the nanosphere lithographic method was
      used. Furthermore, the effects of the structuring of PEDOT: PSS on optical
      properties were also investigated.

PMID- 25971089
TI  - Screen-printed Cu circuit for low-Cost fabrication and its electrochemical
      migration characteristics.
AB  - Circuit pitch has decreased due to the demand for high-performance and multi
      functional electronic devices. This trend has increased the risk of short-circuit
      failures by electrochemical migration (ECM), which is the transportation of ions
      between the cathode and anode under electrical potential. While direct printing
      has emerged as a promising technology in terms of manufacturing cost and
      environmental issues, there are few studies about ECM in directly printed copper
      (Cu) nanopaste. We prepared screen-printed comb-type Cu patterns on a Si wafer
      with various sintering temperatures (200, 250, 300, 350 degrees C). ECM
      characteristics of the printed Cu were determined by water drop testing under
      various electrical potentials (3, 6, 9 V). The microstructures and the roughness
      profiles of the pattern surfaces were identified with field emission scanning
      electron microscopy (FE-SEM) and a three-dimensional surface profiler,
      respectively. While the electrical potential increased from 3 V to 9 V, the time
      to failure (ECM time) required for dendrites to grow from the cathode to the
      adjacent anode decreased by 63.0%. On the other hand, the ECM time increased by
      205.1% when the sintering temperature increased from 200 degrees C to 350 degrees
      C. FE-SEM micrographs and energy-dispersive X-ray spectroscopy analysis of
      dendrites showed a mixture of trunk and lace types, which were mainly composed of
      Cu.

PMID- 25971090
TI  - Improved bipolar resistive switching memory characteristics in Ge0.5Se0.5 solid
      electrolyte by using dispersed silver nanocrystals on bottom electrode.
AB  - Resistive switching random-access memory (ReRAM) devices based on chalcogenide
      solid electrolytes have recently become a promising candidate for future low
      power nanoscale nonvolatile memory application. The resistive switching mechanism
      of ReRAM is based on the formation and rupture of conductive filament (CF) in the
      chalcogenide solid electrolyte layers. However, the random diffusion of metal
      ions makes it hard to control the CF formation, which is one of the major
      obstacles to improving device performance of ReRAM devices. We demonstrate the
      spin-coated metal nanocrystals (NCs) enhance the bipolar resistive switching
      (BRS) memory characteristics. Compared to the Ag/Ge0.5Se0.5/Pt structure,
      excellent resistive switching memory characteristics were obtained from the
      Ag/Ge0.5Se0.5/Ag NCs/Pt structure. Ag NCs improve the uniformity of resistance
      values and reduce the reset voltage and current. A stable DC endurance (> 100
      cycles) and a high data retention (> 10(4) sec) were achieved by spin coating the
      Ag NCs on the Pt bottom electrode for ReRAMs.

PMID- 25971091
TI  - Solution-processed silver nanowire/indium-tin-oxide nanoparticle hybrid
      transparent conductors with high thermal stability.
AB  - In this study, solution-processed hybrid structure transparent conductors
      consisting of silver nanowires (AgNWs) and indium-tin-oxide nanoparticle (ITO-NP)
      layers are investigated. Fabricated transparent conductors had stacked structures
      of ITO-NP/AgNW and ITO-NP/AgNW/ITO-NP, and a successful integration was possible
      on glass substrates. Compared to a single-layered ITO-NP film which has a sheet
      resistance value of 1.31 k Omega/?, a remarkable enhancement in sheet resistance
      was achieved from the hybrid structures, showing sheet resistance values of 44.74
      Omega/? and 28.07 Omega/? for ITO-NP/AgNW and ITO-NP/AgNW/ITO-NP structures,
      respectively. In addition, the ITO-NP/AgNW/ITO-NP triple-layered transparent
      conductor showed greatly enhanced thermal stability in terms of sheet resistance
      and transmittance against a high-temperature environment up to 300 degrees C.
      Based on these results, it can be suggested that the hybrid structure has
      advantages of enhancing both electrical properties of ITO-NP layer and thermal
      stability of AgNW layer, and we believe the hybrid structure transparent
      conductors can be a suitable option for applications which require high
      electrical conductivity, transmittance, and thermal stability.

PMID- 25971092
TI  - F and Ti doped silicate nanocomposite thin films for antimicrobial and easy clean
      applications.
AB  - Titanium isopropoxide (TIPO), tetraethyl orthosilicate (TEOS) and
      Fluoroalkylsilane (FAS) silane precursor were employed to coat transparent thin
      film on the glass substrate and these effectively prevents pollution on the glass
      from microorganisms. The each nanocomposition film was prepared by sol-gel
      method, the solution of nanocomposite was coated by spin coater with 1200 rpm for
      30 sec and cured by thermal at 100 degrees C on glass which surface treated with
      Piranha solution. The nanocomposite films with highly self cleaning efficacy were
      fabricated and studied for various molar compositions of TEOS, TIPO and FAS.
      TEOS/TIPO film in glass substrate shows an optical transparency over 90% up to 30
      mol% of TIPO in TEOS/TIPO composite films and also FAS incorporated up to 4 mol%
      onto TEOS/TIPO films. The anti-microbial efficiency of the nanocomposite film was
      improved 30% when it was exposed under UV light radiation than that in ambient
      condition.

PMID- 25971093
TI  - Electroless nickel alloy deposition on SiO2 for application as a diffusion
      barrier and seed layer in 3D copper interconnect technology.
AB  - Electroless Ni-P films were investigated with the aim of application as barrier
      and seed layers in 3D interconnect technology. Different shapes of blind-via
      holes were fabricated with a deep reactive ion etcher and SiO2 formed on these
      holes as an insulating layer. The surface of the substrate has been made
      hydrophilic by O2 plasma treatment with 100 W of power for 20 min. Electroless Ni
      P films were deposited as both a diffusion barrier and a seed layer for Cu
      filling process. Prior to plating, substrates were activated in a palladium
      chloride solution after sensitization in a tin chloride solution with various
      conditions in order to deposit uniform films in TSV. After the formation of the
      electroless barrier layer, electro Cu was plated directly on the barrier layer.
      Ni-P films fabricated in blind-via holes were observed by scanning electron
      microscope. Energy dispersive spectroscopy line scanning was carried out for
      evaluating the diffusion barrier properties of the Ni-P films. The electroless Ni
      P layer worked well as a Cu diffusion barrier until 300 degrees C. However, Cu
      ions diffused into barrier layer when the annealing temperature increases over
      400 degrees C.

PMID- 25971094
TI  - Optimization of polymeric dispersant concentration for the dispersion-stability
      of magnetite nanoparticles in water solution.
AB  - Fouling of various Fe oxide particulates on heat transfer tubes in the coolant of
      the secondary system of a nuclear power plant has been known to reduce the heat
      transfer performance and degrade the integrity of system components. Thus, in
      order to mitigate such a fouling problem, an addition of polymeric dispersant has
      been proposed to remove the oxide partculates. In this paper, experimental
      studies was conducted for evaluating the effect of polymeric dispersants (PAA:
      Polyacrylic acid, PMA: Polymethacrylic acid, PAAMA: Polymaleic acid-co-acrylic
      acid) on the dispersion stability of magnetite nanoparticles (MNPs, Fe3O4) for
      the reduction of fouling and corrosion of carbon steel by the settling test, the
      transmittance, zeta-potential, and particle size measurements, and the
      electrochemical corrosion tests. It was observed that the critical concentration
      for maximizing the dispersionstability of MNPs was in the range of concentration
      ratio (dispersant/MNPs) of 0.1 to 0.01 and the dispersion-stability of MNPs was
      not improved when the dispersant concentration is above this critical value. This
      non-linearity above a critical dispersant concentration may be explained by the
      agglomerations between MNPs. While there is no significant increase of corrosion
      rate with an addition of up to 10 ppm PAA, the addition of 100 ppm PAA increases
      the growth rate of oxide layer rapidly and deteriorates the formation of
      protective oxide on carbon steel. It is thus reasonably stated that the
      optimization of polymeric dispersants variables and its impacts on the corrosion
      of structural materials is necessary for the best application at plants.

PMID- 25971095
TI  - Etching characteristics and mechanism of SiN(x) films for nano-devices in
      CH2F2/O2/Ar inductively coupled plasma: effect of O2 mixing ratio.
AB  - Etching characteristics and mechanisms of low-temperature SiN(x) thin films for
      nano-devices in CH2F2/O2/Ar inductively-coupled plasmas were studied. The etching
      rates of SiN(x) thin films as well as the etching selectivities over Si and
      photoresist were measured in the range of 25-75% O2 in a feed gas at fixed CH2F2
      content (25%), gas pressure (6 mTorr), input power (900 W), bias power (200 W),
      and total gas flow rate (40 sccm). Plasma parameters were analyzed using the
      Langmuir probe diagnostics and optical emission spectroscopy. The chemical states
      of the etched surfaces were examined by the X-ray photoelectron spectroscopy. It
      was found that the non-monotonic (with a maximum at about 50-60% O2) SiN(x)
      etching rate does not correlate with monotonically decreasing F atom flux and ion
      energy flux. It was proposed that, under the given set of experimental
      conditions, the SiN(x) etching process is also controlled by the O and H atom
      fluxes through the destruction of the fluorocarbon polymer layer.

PMID- 25971096
TI  - Etch characteristics of magnetic tunnel junction materials using bias pulsing in
      the CH4/N2O inductively coupled plasma.
AB  - The etch characteristics of magnetic tunneling junction (MTJ) related materials
      such as CoFeB, MgO, FePt, Ru, and W as hard mask have been investigated as
      functions of rf pulse biasing, substrate heating, and CH4/N2O gas combination in
      an inductively coupled plasma system. When CH4/N2O gas ratio was varied, at
      CH4/N2O gas ratio of 2:1, not only the highest etch rates but also the highest
      etch selectivity over W could be obtained. By increasing the substrate
      temperature, the linear increase of both the etch rates of MTJ materials and the
      etch selectivity over W could be obtained. The use of the rf pulse biasing
      improved the etch selectivity of the MTJ materials over hard mask such as W
      further. The surface roughness and residual thickness remaining on the etched
      surface of the CoFeB were also decreased by using rf pulse biasing and with the
      decrease of rf duty percentage. The improvement of etch characteristics by
      substrate heating and rf pulse biasing was possibly related to the formation of
      more stable and volatile etch compounds and the removal of chemically reacted
      compounds more easily on the etched CoFeB surface. Highly selective etching of
      MTJ materials over the hard mask could be obtained by using the rf pulse biasing
      of 30% of duty ratio and by increasing the substrate temperature to 200 degrees C
      in the CH4/N2O (2:1) plasmas.

PMID- 25971097
TI  - Effects of microstructure and deformation conditions on the hot formability of Ni
      Ti-Hf shape memory alloys.
AB  - Ingots of Ni-Ti-Hf shape memory alloys were prepared by vacuum arc re-melting.
      Isothermal hot compression tests were conducted at temperatures ranging from 700
      to 1000 degrees C and at strain rates from 10(-2) s(-1) to 1.0 s(-1). A decrease
      in the Ni content below 50.2 at.% significantly deteriorated the hot workability
      due to the formation of a brittle second phase. Also, the low Ni content alloy
      showed poor workability when the temperature exceeded 900 degrees C. Additional
      compression tests were conducted under various conditions to clarify the effects
      of the chemical composition, solidification anisotropy, and the strain rate.

PMID- 25971098
TI  - Theoretical analysis for quantitative evaluation of in-situ nanoparticle
      measurement probability.
AB  - A probability equation based on the proper assumptions of the particle trajectory
      and fundamental physics has been developed by analyze beam properties such as
      beam width and intensity distribution for an in situ particle monitor (ISPM). The
      radius coordinate which has the same intensity and portion of beam area for
      detection voltage range were analyzed to calculate particle measurement
      probability. The particle measurement probability is defined at a ratio of entire
      beam area to specified beam area which decided by detection voltage range. A
      probability measurement, given as a function of the detection voltage range, was
      performed 5 times using 200, 300, 500, 700 nm polystyrene latex standard
      particles at a pressure of 100 Torr with an in-house ISPM. The theoretical
      calculation results show good agreement with the experimental results and the
      maximum error is 20% by calculating probability differences between theoretical
      and experimental values. A calibration method based on the proposed probability
      equation enables to developed and increase accuracy of ISPM.

PMID- 25971099
TI  - Effect of thiourea on electrochemical nucleation and electrochemical impedance
      spectroscopy of electrodeposited tin on a copper substrate in a sulfate bath.
AB  - The effect of thiourea on the electrochemical nucleation of tin on a copper
      substrate from a sulfate bath was studied using voltammetry, chronoamperometry,
      electrochemical impedance spectroscopy, and scanning electron microscopy. Without
      thiourea, electrodeposition of tin showed very poor surface coverage. However, re
      nucleation and growth of tin occurred after the addition of thiourea. In
      particular, very rapid re-nucleation and growth behavior of tin were observed
      when up to 6 g/L of thiourea was added. Furthermore, impedance analysis allowed
      the estimation of the change in the growth behavior of tin when up to 6 g/L of
      thiourea was added.

PMID- 25971100
TI  - Determination of sulfuric acid concentration for anti-cavitation characteristics
      of Al alloy by two step anodizing process to forming nano porous.
AB  - Al alloy is a highly active metal but forms a protective oxide film having high
      corrosion resistance in atmosphere environment. However, the oxide film is not
      suitable for practical use, since the thickness of the film is not uniform and it
      is severly altered with formation conditions. This study focused on developing an
      aluminum anodizing layer having hardness, corrosion resistance and abrasion
      resistance equivalent to a commercial grade protective layer. Aluminum anodizing
      layer was produced by two-step aluminum anodizing oxide (AAO) process with
      different sulfuric acid concentrations, and the cavitation characteristics of the
      anodized coating layer was investigated. In hardness measurement, the anodized
      coating layer produced with 15 vol.% of sulfuric acid condition had the highest
      value of hardness but exhibited poor cavitation resistance due to being more
      brittle than those with other conditions. The 10 vol.% of sulfuric acid condition
      was thus considered to be the optimum condition as it had the lowest weight loss
      and damage depth.

PMID- 25971101
TI  - Corrosion resistance of ultrasonic electrodeposited Ni-Co-Fe ternary alloy films
      according to current density.
AB  - Ni-Co-Fe ternary alloy films were deposited on Copper clad laminate (CCL) by
      ultrasonic electroplating at different current densities from a sulfate bath. The
      corrosion properties of the ultrasonically-electrodeposited Ni-Co-Fe films were
      investigated by electrochemical impedance spectroscopy (EIS). We found that Ni,
      Co, and Fe component ratios changed according to the current density. The Ni
      content increased when the current density increased, but the Co and Fe content
      of the films decreased. Ni-Co-Fe ternary alloy films with a high Ni content and
      lower Fe content showed good resistance to corrosion. We also found that
      ultrasonically-electrodeposited Ni-Co-Fe films had higher corrosion resistance
      than non-ultrasonically electrodeposited Ni-Co-Fe films. Ultrasonically
      electrodeposited Ni-Co-Fe films had a higher Ni content than electrodeposited Ni
      Co-Fe ternary alloys. X-ray diffraction analysis revealed that the Ni-Co-Fe films
      comprised a mixture of both FCC (face centered cubic) and BCC (body centered
      cubic) structures.

PMID- 25971102
TI  - Microstructural and chemical properties of ZnO films formed using
      electrodeposition.
AB  - We investigated the effect of bath temperature and electrodeposition potential on
      the microstructural and chemical properties of ZnO films formed on Mo-coated soda
      lime glass substrates using electrodeposition. The electrodeposition was
      performed using an electrolytic solution containing 0.05 M Zn(NO3)2 for 6 min.
      The ZnO islands grew larger to impinge with other islands until the bath
      temperature was increased up to 40 degrees C, above which continuous ZnO film was
      eventually formed. An increase in the electrodeposition potential resulted in
      enhancement of the growth rate of the electrodeposited ZnO film with the
      facilitation of film texturation. The c-axis was perpendicular to surface, which
      could be associated with the preferential orientation along the (002) direction.
      At the electrodeposition potential of -1.3 V (vs. a saturated calomel electrode),
      significant amounts of hydrogen bubbles that electrochemically evolved near the
      surface of the working electrode hampered the homogenous growth of the ZnO film,
      which could be responsible for morphological degradation of the ZnO film.

PMID- 25971103
TI  - Scale effects on stiction-induced release voltage shift of nano-electromechanical
      (NEM) memory cells.
AB  - In order to overcome the limits of conventional flash memory, nonvolatile nano
      electromechanical (NEM) memory has been proposed. The release voltage shift of a
      NEM memory cell induced by beam stiction has been studied by using one
      dimensional analytical model and three-dimensional finite element analysis (FEA)
      simulation. As the size of a NEM memory cell decreases, stiction effects become
      more severe because the spring force becomes weaker. The influence of NEM memory
      cell scaling on release voltage shift has been discussed. If all geometrical
      dimensions are scaled in proportion, which is called general scaling, release
      voltage shift becomes larger, and release voltage becomes smaller. Then, if
      release voltage shift becomes larger than release voltage as general scaling
      continues, NEM memory cells do not work due to the permanently pulled-in
      cantilever beam. In order to prevent this, it is necessary to reduce beam length
      aggressively compared with other dimension scaling or to introduce more elastic
      and less adhesive beam material than existing beam material.

PMID- 25971104
TI  - Nanoetching process on silicon solar cell wafers during mass production for
      surface texture improvement.
AB  - Major challenge in nanotechnology is to improve the solar cells efficiency. This
      can be achieved by controlling the silicon solar cell wafer surface structure.
      Herein, we report a KOH wet etching process along with an ultrasonic cleaning
      process to improve the surface texture of silicon solar cell wafers. We evaluated
      the KOH temperature, concentration, and ultra-sonication time. It was observed
      that the surface texture of the silicon solar wafer changed from a pyramid shape
      to a rectangular shape under edge cutting as the concentration of the KOH
      solution was increased. We controlled the etching time to avoid pattern damage
      and any further increase of the reflectance. The present study will be helpful
      for the mass processing of silicon solar cell wafers with improved reflectance.

PMID- 25971105
TI  - Effect of hydrogen plasma on electroless-plating Ni-B films and its Cu diffusion
      barrier property.
AB  - Electroless-plating Ni-B films have been evaluated for the application as the
      diffusion barrier and metal cap for copper integration. The effect of post plasma
      treatment in a hydrogen environment on the characteristics of Ni-B films such as
      chemical composition, surface roughness, crystallinity, and resistivity was
      investigated. By treating electroless-plating Ni-B films with H2 plasma, the
      resistance and the roughness of the films decreased. The leakage current of Ni-B
      bottom electrode/30-nm-thick Al2O3/Al top electrode structures improved after the
      H2 plasma treatment on the Ni-B films. 40 nm-thick electroless-plating Ni-B film
      was able to block Cu diffusion up to 350 degrees C.

PMID- 25971106
TI  - Thermal compression chip interconnection using organic solderability preservative
      etched substrate by plasma processing.
AB  - The solderability of copper organic solderbility preservative (CuOSP) finished
      substrate was enhanced by the plasma etching. To improve the solderability of TC
      interconnection with the CuOSP finished substrate, the plasma etching process is
      used. An Oxygen-Hydrogen plasma treatment process is performed to remove OSP
      material. To prevent the oxidation by oxygen plasma treatment, hydrogen reducing
      process is also performed before TC interconnection process. The thickness of OSP
      material after plasma etching is measured by optical reflection method and the
      component analysis by Auger Electron Spectroscopy is performed. From the lowered
      thickness, the bonding force of TC interconnection after OSP etching process is
      lowered. Also the electrical open/short test was performed after assembling the
      completed semiconductor packaging. The improved yield due to the plasma etching
      process is achieved.

PMID- 25971107
TI  - Characteristics of pulsed internal inductively coupled plasma for next generation
      display processing.
AB  - RF pulsed plasma characteristics of inductively coupled plasma (ICP) sources
      operated with internal linear type antennas for the next generation display
      processing were investigated. By applying the rf pulse mode in the ICP source,
      with decreasing the rf pulse duty percentage, the average electron temperature
      was decreased and the plasma non-uniformity was improved with decreasing the rf
      pulse duty percentage. In the case of plasma uniformity, for the same time
      average rf power of 3 kW to the ICP source, the plasma non-uniformity was
      improved from 8.4% at 100% of rf duty percentage to 6.4% at 60% of rf duty
      percentage due to the increased diffusion of the plasma during the pulse-off
      time. When SiO2 was etched using CF4, the etch rate uniformity was also improved
      due to the improvement of plasma uniformity.

PMID- 25971108
TI  - Writing and erasing mechanisms of stable nonvolatile memory devices based on SnO2
      nanoparticle/polystyrene nanocomposites.
AB  - X-ray photoelectron spectroscopy spectra and transmission electron microscopy
      images showed that SnO2 nanoparticles were randomly distributed in the
      polystyrene (PS) layer. Capacitance-voltage (C-V) measurements on the Al/SnO,
      nanoparticles embedded in PS layer/p-Si devices at 300 K showed a clockwise
      hysteresis with a large flatband voltage shift due to the existence of SnO2
      nanoparticles. Capacitance-time measurements showed that the devices exhibited
      excellent memory retention characteristics at ambient conditions. The writing and
      the erasing mechanisms for the Al/SnO, nanoparticles embedded in PS layer/p-Si
      devices are described on the basis of the C-V results and energy band diagrams.

PMID- 25971109
TI  - Lasing characteristics of InP-based InAs quantum dots depending on InGaAsP
      waveguide conditions.
AB  - We report the influences of a dot-in-a-well structure with a thin GaAs layer and
      the thickness of a waveguide (WG) on the lasing characteristics of InAs quantum
      dots (QDs) based on InP. The QD laser diodes (QDLDs) consist of seven-stacked
      InAs QDs separated by a 10 nm-thick InGaAsP (1.15 MUm, 1.15Q-InGaAsP) layer,
      which is further sandwiched by a 800 nm-thick 1.15Q-lnGaAsP WG (reference QDLD).
      For comparison, the InAs QDs were inserted into the InGaAsP (1.35 MUm, 1.35Q
      InGaAsP) quantum well embedded in the 1.15Q-InGaAsP matrix at the active layer.
      And a 2 monolayer (ML)-thick GaAs layer was additionally introduced right before
      the QD layer (GDWELL-LDs). Lasing emission from the reference QDLD with only the
      1.15Q-InGaAsP structure was not observed at room temperature (RT). However, the
      lasing emission from the GDWELL-LDs was clearly observed at the wavelength of
      1.46 MUm at RT under continuous-wave (CW) mode. The threshold current density of
      the GDWELL-LD with the 800 nm-thick InGaAsP WG was measured to be 830 A/cm2,
      which was lower than that of the GDWELL-LD with the 200 nm-thick WG (900 A/cm2).
      Also, the slope efficiency of the GDWELL-LD was significantly improved with
      increasing thickness of the InGaAsP WG.

PMID- 25971110
TI  - Preparation and properties of hollow fiber membranes for removing virus and
      bacteria.
AB  - In this study, polysulfone hollow fiber membrane was successfully prepared by
      phase inversion method for separation of virus and bacteria. When we prepare the
      hollow fiber membrane, we controlled various factors such as the polymer
      concentration, air gap and internal coagulation to investigate effect to membrane
      property. Morphology of surface and cross section of membrane were measured by
      field emission scanning electron microscope (FE-SEM). Water flux of membrane was
      measured using test modules. Mean pore diameter of membrane was calculated using
      rejection of polystyrene (PS) latex beads for separation of virus and bacteria.
      Flux and mean flow pore diameter of prepared membrane show 800 L/mh, 0.03 MUm at
      1.0 kgf/cm2. The bacteria removal performance of prepared UF membranes was over 6
      logs

PMID- 25971111
TI  - Surface modification and characterization of electrosprayed Sn-doped In2O3 thin
      films.
AB  - We synthesized Sn-doped In2O3 (Indium tin oxide, ITO) thin films using
      electrospray and spin-coating. Scanning electron microscopy, atomic force
      spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Hall-effect
      measurement, and UV-vis spectrophotometry measurements were performed to
      investigate the morphological, structural, chemical, electrical, and optical
      properties of the electrosprayed ITO films with a sol-layer coating for surface
      modification. To obtain the optimum performance of the resultant ITO thin films
      after surface modification, we heat-treated them at four different temperatures
      of 450 degrees C (sample A), 550 degrees C (sample B), 650 degrees C (sample C),
      and 750 degrees C (sample D) using microwave heating. Surface modified ITO thin
      films calcined at 550 degrees C (sample B) using electrospray and spin-coating
      are observed to have superior resistivity (9.9 x 10(-3) 2 Omega x cm) and optical
      transmittance (-92.08%) owing to the improved densification of the ITO surface by
      spin-coating and the formation of uniform ITO thin films by electrospraying.

PMID- 25971112
TI  - Surface nanocrystallization of pure Cu induced by ultrasonic shot peening.
AB  - Peening is mainly used as a method of surface treatment for microstructural
      modification in order to improve surface mechanical properties. The ultrasonic
      shot peening (USP) technique can cause severe plastic deformation with its high
      strain rate on the surface of metallic parts. However, systematic studies of
      microstructural refinement mechanism upon plastic deformation with consideration
      of alloy systems are rare. In this study, USP-treated Cu samples of 99.96% purity
      was examined using analytical techniques, Vickers microhardness test, electron
      backscattered diffraction (EBSD) and transmission electron microscopy (TEM).
      Results of EBSD and microhardness analyses indicated grain refinement with
      deformation structures and hardness increase down to 400 MUm in depth upon
      treatment. Depth specific TEM analysis of the samples revealed the steps of the
      grain refinement process to the formation of randomly oriented fine grains.

PMID- 25971113
TI  - Colorless and transparent copolyimide nanocomposites.
AB  - Copolyimides (Co-PIs) were synthesized from 2,2'-bis(trifluoromethyl) benzidine
      (TFB) and different ratios of 4,4'-(hexafluoroisopropylidene) diphthalic
      anhydride (6FDA) and pyromellitic dianhydride (PMDA). The Co-PI films were
      obtained from poly(amic acid) (PAA) by solution-casting through typical chemical
      and thermal imidizations. The thermal properties and optical transparency of the
      Co-PI films with various PMDA monomer contents were investigated. It was found
      that with increasing PMDA content, the thermal transition temperatures of the Co
      PI films increased. Co-PI nanocomposites were prepared with various amounts of
      organically modified hectorite (STN) on a TFB:6FDA:PMDA = 1.0:0.9:0.1 mole ratio
      Co-PI hybrid film to examine the thermal properties, morphology, and optical
      transparency. The thermo-optical properties of the Co-PI hybrid films
      deteriorated with increasing clay content. However, the coefficient of thermal
      expansion (CTE) and oxygen barrier properties of the PI hybrid films improved
      with increasing clay content.

PMID- 25971114
TI  - A study on electron impact dissociative ionization of organosilicon precursors
      for plasma processing.
AB  - We discussed the electron impact dissociation behavior of the organosilicon
      molecules with methyl groups, based on the fragment pattern and molecular-orbital
      calculation of the bond dissociation energies for the molecules. From the
      calculation of bond dissociation energy of the organosilicon molecules, methyl
      groups, which bonded directly to the silicon atom, were found to have the
      weakest. Regarding the fragment patterns of the reactants investigated by a
      quadrupole mass spectrometer, the hexamethyldisiloxane was harder to dissociate
      than the trimethylmethoxysilane due to the strong Si-O bonding force, which also
      affected the dissociation in the plasma. From the above considerations,
      dissociation reactions by electron impact could be partly identified.

PMID- 25971115
TI  - Effect of confining pressure due to external jacket of steel plate or shape
      memory alloy wire on bond behavior between concrete and steel reinforcing bars.
AB  - For external jackets of reinforced concrete columns, shape memory alloy (SMA)
      wires are easy to install, and they provide active and passive confining
      pressure; steel plates, on the other hand, only provide passive confining
      pressure, and their installation on concrete is not convenient because of the
      requirement of a special device. To investigate how SMA wires distinctly impact
      bond behavior compared with steel plates, this study conducted push-out bond
      tests of steel reinforcing bars embedded in concrete confined by SMA wires or
      steel plates. For this purpose, concrete cylinders were prepared with dimensions
      of 100 mm x 200 mm, and D-22 reinforcing bars were embedded at the center of the
      concrete cylinders. External jackets of 1.0 mm and 1.5 mm thickness steel plates
      were used to wrap the concrete cylinders. Additionally, NiTiNb SMA wire with a
      diameter of 1.0 mm was wound around the concrete cylinders. Slip of the
      reinforcing bars due to pushing force was measured by using a displacement
      transducer, while the circumferential deformation of specimens was obtained by
      using an extensometer. The circumferential deformation was used to calculate the
      circumferential strains of the specimens. This study assessed the radial
      confining pressure due to the external jackets on the reinforcing bars at bond
      strength from bond stress-slip curves and bond stress-circumferential strain
      curves. Then, the effects of the radial confining pressure on the bond behavior
      of concrete are investigated, and an equation is suggested to estimate bond
      strength using the radial confining pressure. Finally, this study focused on how
      active confining pressure due to recovery stress of the SMA wires influences bond
      behavior.

PMID- 25971116
TI  - The effect of hydrophilic photoacid generator on acid diffusion in chemical
      amplification resists.
AB  - A photoacid generator (PAG) is a component of chemical amplification photoresists
      (CAR). The most widely used PAG in CAR system is triphenyl onium salt which is
      well known to one of the best leaving groups from various radiation. Acid
      diffusion influences resist characteristics in area such as resolution and
      linewidth control. The structure of the hydrophilic PAG was designed to restrict
      acid diffusion within the photoresist. Acid amplification was suppressed by the
      hydroxyl group-acid interaction. Novel PAGs with functional groups were
      synthesized and characterized. Poly(GMA-co-MMA) was synthesized with a
      combination of crosslinkable glycidyl methacrylate (GMA) and highly refractive
      methyl methacrylate (MMA). The synthesized polymers were confirmed by NMR and FT
      IR, and their thermal properties were studied using TGA and DSC. The resists were
      evaluated as a positive type resist for ArF lithography. PAGs exhibited good acid
      generation efficiency with controlled acid diffusion. We found that the energy
      latitude property of the photoresist was improved with hydroxyl-PAG.

PMID- 25971117
TI  - Effect of material properties on stability of silver nanoparticles in water.
AB  - Increased production and use of silver nanoparticles (AgNPs) could potentially
      lead to their release into the environment. Estimating the exposure to engineered
      nanomaterials in the environment is essential for assessing their risk. This
      study examined the aggregation and sedimentation kinetics behaviors of citrate-
      (Cit-AgNPs) and polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) with
      three different average sizes in calcium chloride (CaCl2) solutions, emphasizing
      the effects of particle size and type of coating material on both behaviors. As
      the ionic strength increased, Cit-AgNPs (stabilized by charge repulsion)
      aggregated rapidly and settled down, while PVP-AgNPs (stabilized by steric
      repulsion) did not aggregate, even at an ionic strength of 10 mM CaCl2, due to
      likely steric hiderance effects of PVP coating. Interestingly, however, PVP-AgNPs
      sedimented without aggregating within 7 days and this tendency seems to having
      relevance to the particle size. These results suggest that the particle size and
      type of coating material play important roles in determining nanoparticle fate
      and transport.

PMID- 25971118
TI  - On the etching characteristics and mechanisms of HfO2 thin films in CF4/O2/Ar and
      CHF3/O2/Ar plasma for nano-devices.
AB  - The study of etching characteristics and mechanisms for HfO2 and Si in CF4/O2/Ar
      and CHF3/O2/Ar inductively-coupled plasmas was carried out. The etching rates of
      HfO2 thin films as well as the HfO2/Si etching selectivities were measured as
      functions of Ar content in a feed gas (0-50% Ar) at fixed fluorocarbon gas
      content (50%), gas pressure (6 mTorr), input power (700 W), bias power (200 W),
      and total gas flow rate (40 sccm). Plasma parameters as well as the differences
      in plasma chemistries for CF4- and CHF3-based plasmas were analyzed using
      Langmuir probe diagnostics and 0-dimensional plasma modeling. It was found that,
      in both gas systems, the non-monotonic (with a maximum at about 15-20% Ar) HfO2
      etching rate does not correlate with monotonic changes of F atom flux and ion
      energy flux. It was proposed that, under the given set of experimental
      conditions, the HfO2 etching process is affected by the factors determining the
      formation and decomposition kinetics of the fluorocarbon polymer layer. These
      factor are the fluxes of CF(x) (x = 1, 2) radicals, O atoms and H atoms.

PMID- 25971119
TI  - Effect of RF pulsing biasing on the etching of magnetic tunnel junction materials
      using CH3OH.
AB  - The magnetic tunnel junction (MTJ)-related materials such as CoFeB, CoPt, MgO,
      and Ru, and W were etched using CH3OH in a pulse-biased inductively coupled
      plasma system and the effect of bias pulsing (100% 30% duty percentage) on the
      etch characteristics of the MTJ-related materials was investigated at the
      substrate temperature of 200 degrees C. The etch selectivity of MTJ-related
      materials over W was improved by using pulse-biasing possibly due to the
      formation of more stable and volatile etch products during the pulse-off time and
      the removal of the compounds more easily on the etched CoFeB surface during the
      pulse-on time. X-ray photoelectron spectroscopy also showed that the use of lower
      duty percentage decreases the residue thickness remaining on the etched MTJ
      materials indirectly indicated the higher volatility of the etch products by the
      bias pulsing. The etching of nano-patterned CoFeB masked with W also showed more
      anisotropic etch profile by pulse-biasing probably due to the increased the etch
      selectivity of CoFeB over W and the decreased redeposition of etch products on
      the sidewall of the CoFeB features. The most anisotropic CoFeB etch profiles
      could be observed by using CH3OH gas in the pulse biasing of 30% duty ratio.

PMID- 25971120
TI  - [Features of coagulative blood potential disorder in acute constitutional
      inflammatory response of septic tubo-ovarian formations].
AB  - BACKGROUND: There are no any systemized studies of relationship between the
      coagulative haemostasis' disorders and metabolic and cytokine status in patients
      with septic tuboovarial formations. OBJECTIVE: The aim of the present work was to
      study the mechanisms of blood coagulation disorders and their relationships with
      changes of cytokine status and acute phase of inflammatory response in septic
      tubo-ovarian formations in women. METHODS: 32 patients with purulent tubovarial
      formations and 30 healthy women were examined. RESULTS: Shortening of activated
      partial thromboplastin, prothrombin and thrombin clotting time, increasing the
      duration of XIIa-kallikrehin-dependent fibrinolysis, as well as the elevation of
      paracoagulation products in blood plasma were observed. IL-1beta (p =0.000023),
      TNF-alpha (p <0.001), C-reactive protein (p <0.001), haptoglobin (p <0.001) and
      fibrinogen (p <0.001) levels were higher in peripheral blood of patients in
      comparison with healthy women. Accumulation of lipid hydroperoxides (p <0. 001)
      and malonic dialdehyde (p <0.001) occurred in the blood plasma of patients. Serum
      albumin (p <0.001) and transferring (p <0.001) levels were lesser in patients
      with purulent tubo ovarial formations in comparison with healthy women.
      CONCLUSION: The obtained results showing an initiating role of cytokine and
      oxidative metabolic status changes in blood coagulation potential's and
      fibrinolysis activity's disorders developing. This biochemical signs may be used
      as objective criteria which may serve to determine the risk of thrombosis in case
      of acute inflammatory response in women with purulent inflammation.

PMID- 25971121
TI  - [Evaluation of lipid peroxidation - antioxidant protection in perimenopausal
      women with sleep disorders].
AB  - OBJECTIVE: Our aim was to assess lipid peroxidation - antioxidant protection with
      the definition of the oxidative stress coefficient in perimenopausal women with
      sleep disorders. METHODS: 45 perimenopausal women (mean age 49.1+/-0.32) were
      examined: 26 patients with sleep disorders, 19 - without sleep disorders.
      Evaluation of sleep disorders was conducted using a questionnaire of Stanford
      Centre for the Study of Sleep, test for assessment subjective severity of
      insomnia, the questionnaire for the quantitative assessment of the risks of sleep
      apnea, the scale for quantifying the degree of daytime sleepiness Epworth. We
      used spectrophotometric methods for lipid peroxidation - antioxidant system
      investigation. Statistical analysis was performed by non-parametric tests.
      RESULTS: In perimenopausal women sleep disorders often presents falling asleep
      difficulties (93.3%) and morning awakening difficulties (78.8%). Complaints of
      snoring detected in 33.3% of patients. Insomnia severity index was 21.3+/-0.54,
      the total score on the Epworth scale - 12.2+/-0.42. The study results showed
      increase of secondary products of lipid peroxidation (ketodienes and coupled
      trienes) levels by 2.2 times (p <0.05). Coefficient oxidative stress in women
      with sleep disorders is higher by 2 times than in group without sleep disorders.
      CONCLUSION: In perimenopausal women sleep disorders are associated with oxidative
      stress, which is pathogenic rationale for inclusion in the complex therapy of
      these patients drugs that inhibit of lipid peroxidation activation.

PMID- 25971122
TI  - [Ontogenetic aspects of changing lysozyme activity under acute somatic pain].
AB  - OBJECTIVE: Ouraim was to study influence of acute somatic pain on lysozyme
      activity of rats of different age: newborn, rats after eye opening, rats at the
      age of a month, adult and old rats. METHODS: Lysozyme activity was checked before
      pain irritation and 2, 30, 60, 120, 180min afterwards using Dorofeychuk's method
      in our modification. Pain effect was modeling by electrical stimulation. RESULTS:
      activity of lysozyme was 0. 434+/-0. 01 units in intact newborn rats, It was
      higher than in adult rats - 0.260 +/-0.01 units (p <0.001) and it was unchanged
      during the experiment. We found low lysozyme activity in rats after eye opening -
      0.015+/-0.003 units and it was stable during the experiment. Rats at the age ofa
      month had diphasic reaction: lysozyme activity was 0.191+/-0.01 units in intact
      rats, it increased up to 0.378+/-0.01 units (p <0.001) in 2 min after painful
      irritation and it decreased up to 0.113+/-0.02 units (p <0.001) in 30 min.
      Lysozyme activity was 0.260+/-0.01 units. Single-phase reaction was determined
      after acute painful irritation: increase of lysozyme activity after acute somatic
      pain up to 0,450+/-0,014 units (p <0.001). Lysozyme activity was 0.246+/-0.02
      units in blood plasma of old rats. It decreased up to 0.1701+/-0.01 units (p
      <0.01) after painful irritation and it was 0.387+/-0.01 (p <0.001) in the end of
      the experiment. CONCLUSION: Response on pain irritation has differences in
      different groups. The common vector of pain response was the increase of lysozyme
      activity in rats at the age of a month, adult rats, rats after eye opening and
      old rats. Reaction of increasing lysozyme activity was strongly detected in adult
      rats. The results demonstrate preventive lasozyme resistance to potential tissue
      damage or contamination.

PMID- 25971123
TI  - [Features of structural and functional changes of the myocardium in patients with
      chronic viral hepatitis].
AB  - OBJECTIVE: Our aim was to evaluate the characteristics of structural and
      functional changes of the heart in patients with chronic viral hepatitis.
      METHODS: The study included 123 patients - 17 patients with aviraemnia after
      antiviral therapy (group 1), 38 patients with laboratory inactive hepatitis
      (group 2), 68 patients with biochemical active hepatitis (group 3). All patients
      had standard echocardiography, Doppler sonography and tissue Doppler
      echocardiography. RESULTS: Patients with chronic viral hepatitis were revealed to
      develop changes in the geometry of the left ventricle (increase in the wall
      thickness). Patients with active hepatitis had increase in the left atrium, the
      right ventricle and indexed left ventricular mass of the heart. Significant
      morphological changes were not confirmed statistically in patients after
      "therapy". Pulmonary hypertension was revealed in 19% of cases, mitral valve
      prolapse was confirmed in 48%, with the detection rates being not dependent on
      hepatitis activity. Abnormal left ventricular remodeling was identified in 45% of
      patients, in patients with active hepatitis more frequently. Compliance
      dysfunction of both right and left ventricles was detected, it depends on the
      activity of the inflammatory process in the liver. This disorder partially
      persists after antiviral treatment. CONCLUSION: Specifics of the structural and
      functional changes of the heart in patients with chronic viral hepatitis is the
      development of left ventricular hypertrophy, and in the presence of laboratory
      activity hepatitis - relative dilatation of the right heart and ventricular
      diastolic dysfunction of the heart. Carrying out specific antiviral therapy has a
      beneficial effect on cardiac hemodynamics parameters. Method of tissue Doppler
      echocardiography was efficient in evaluation of early disorders of diastolic
      function in patients with chronic viral hepatitis.

PMID- 25971124
TI  - [Trends of infant and child mortality in the Russian Federation in the period of
      1990-2012].
AB  - OBJECTIVE: Dynamics and causes of infant and child mortality in the Russian
      Federation in post-Soviet period (1990-2012) under conditions of demographic
      policy implementation and healthcare system reforming are presented. METHODS:
      Federal State Statistics Service's official statistics data (1990-2012) had been
      analyzed. The data was compared with similar rates of European Union countries.
      RESULTS: It's been revealed that infant mortality decreased (more than in 2
      times) (from 17.4 per thousand to 8.6 per thousand) through all its level
      indicators (early neonatal, neonatal, post-neonatal mortality) and due to almost
      all basic reasons (perinatal disorders, infectious diseases, respiratory
      diseases, congenital anomalies, accidents). Infant mortality rate in rural areas
      is higher (10.1 per thousand and 8.1 per thousand), however, the gap between
      rates in rural regions and in cities is decreasing. In Russian Federation the
      infant mortality has regional distinctions, thus Siberian and Far Eastern regions
      are the least advantaged areas. Mortality of children under 5y.o. is declining
      (from 21.3 per thousand to 10.6 per thousand), but its rate is still higher than
      in European Union countries (3.5 per thousand). External factors occupy the top
      position as a death cause of infants and toddlers; the number of clinical cases
      with a diagnosis of malignant neoplasm increases. CONCLUSION: Thus, improving of
      the system of motherhood and childhood protection in the Russian Federation has
      resulted in significant reduction of infant and child mortality rate.

PMID- 25971125
TI  - [Assessment of the life quality in children with phenylketonuria].
AB  - BACKGROUND: Phenylketonuria (PKU) - the most common inherited disorder of amino
      acid metabolism, identified in Russia by neonatal screening. The results of
      dietary treatment demonstrate a positive effect. However, the quality of PKU
      patients life remains unknown. OBJECTIVE: The aim of the study was to assess the
      quality of PKU children life in comparison with their healthy peers, also
      depending on the treatment onset and the patient's age. METHODS: The study
      involved 64 pairs - PKU child and one of his parents. It was used the common
      questionnaire survey Pediatric Quality of Life Inventory (PedsQLtm4. 0, Varni et
      al., USA, 2001) and the program SPSS v. 14.0 (US) for statistical processing of
      the results. RESULTS: The statistically significant (p <0.001) differences
      between PKU patients and healthy children in the physical, emotional, social and
      role functioning were found. The most pronounced differences were observed in the
      social (70 points vs 90 respectively) and role (57.5 vs 80 respectively)
      functioning. Maximum significant correlation (p <0.001) was installed between the
      social functioning of PKU patients and timing of the dietary treatment. Also the
      statistically significant interaction (p <0.05) was found between the role
      functioning, patient's age and treatment onset. The assessment points of social
      and role functioning were higher (p <0.05) in the PKU patients subgroup with
      early treatment initiation. CONCLUSION: These results confirmed the need of early
      diagnostics of PKU and initiation of dietary treatment, as well as the
      organization of timely psychological support for parents of sick children.

PMID- 25971126
TI  - [Chronic hepatitis C in children: problems and prospects].
AB  - The analysis of a problem state of chronic hepatitis C in children was conducted.
      Data on primary incidence of chronic hepatitis C at the children's population as
      on the territory of the Russian Federation, and abroad are submitted. Problems of
      diagnosis of a HCV infection are studied. The survey analysis of risk of
      contamination is carried out, possible ways of transfer are highlighted, features
      of a course of a HCV infection in children are shown, synchronising frequency of
      a process is displayed. The problem is analysed now, and further prospects in
      treatment of chronic viral hepatitis C in children are estimated.

PMID- 25971128
TI  - [Confocal laser endomicroscopy of gastrointestinal tract: history, problems and
      perspectives in children].
AB  - In this review history, principles, technique and clinical applications of
      confocal laser endomicroscopy are briefly described. This technology allows to
      expand the diagnostic ability of traditional white light endoscopy and to assess
      effectiveness of therapeutic procedures in different gastrointestinal diseases.
      New experimental and clinical data in assessing small bowel barrier dysfunction
      as a predictor of relapse for inflammatory bowel disease is presented. Problems
      and perspectives regarding application of optical biopsy for gastrointestinal
      tract in pediatric practice are discussed.

PMID- 25971127
TI  - [History case of multiple hepatic adenomas in adolescent with severe course of
      glycogen storage disease type lb].
AB  - We represented a case history of multiple hepatic adenomas in an adolescent with
      severe clinical course of glycogen storage disease type lb (compound heterozygous
      mutations c.1042_1043delCT and c.817G>A in the SLC37A4). The patient was
      prescribed a raw cornstarch and hepatoprotectors therapy, but he and his parents
      had low compliance to treatment. At the age of 13,5 years ultrasound
      investigation and computed tomography revealed multiple adenomas. Due to the
      severe condition of the patient it was impossible to perform focal hepatic
      biopsy. At present time the patient receives treatment focused on correction of
      metabolic disturbances, thereafter an applicability of exploratory puncture will
      be settled for the further patient surveillance. The modern data on causes and
      risk factors of hepatic adenomas in such patients, the possibility of their
      malignization, the algorithm of the follow-up and the methods of treatment are
      presented in the discussion.

PMID- 25971129
TI  - [Predictive value of Hodgkin's lymphoma tumor burden in present].
AB  - Today approximately 70% of patients with Hodgkin lymphoma can be cured with the
      combined-modality therapy. Tumor burden, the importance of which was demonstrated
      15 years ago for the first time, is a powerful prognostic factor. Data of
      literature of representations on predictive value of Hodgkin's lymphoma tumor
      burden are shown in the article. The difficult immunological relations between
      tumor cells and reactive ones lead to development of the main symptoms.
      Nevertheless, the collective sign of tumor burden shows the greatest influence on
      survival and on probability of resistance, which relative risk can be predicted
      on this variable and treatment program. Patients with bulky disease need
      escalated therapy with high-dose chemotherapy. Integration into predictive models
      of the variable will change an expected contribution of clinical and laboratory
      parameters in the regression analyses constructed on patients with Hodgkin's
      lymphoma. Today the role of diagnostic functional methods, in particular a
      positron emission tomography, for metabolic active measurement is conducted which
      allows excluding a reactive component.

PMID- 25971130
TI  - [Ethnic aspects of hereditary breast cancer in the region of Siberia].
AB  - BACKGROUND: Ethnic diversity of the population in the region of Siberia suggests
      the existence of different germline mutations in the BRCA1/2 genes associated
      with breast and ovarian cancer in different ethnic populations, but spectrum of
      these mutations has not been studied. OBJECTIVE: Our aim was to evaluate the
      frequency of the most common mutations BRCA1/2 (BRCA1 5382insC, BRCA1 185delAG,
      BRCA1 4153delAG, BRCAI T300G, BRCA2 6174delT) in women diagnosed with breast
      cancer among indigenous people and newcomers living in Siberia. METHODS: We
      tested 1281 genomic DNA samples for the presence of BRCA1 5382insC mutation in
      patients diagnosed with breast cancer considering no family history. 72 patients
      having hereditary cancer signs were tested for the mutations BRCA1 185delAG,
      BRCA1 4153delAG, BRCA1 T300G, BRCA2 6174delT. RESULTS: Out of 765 patients of
      Slavic ethnic group, 27 women (3.5%) were carriers of allele BRCA1 5382insC. The
      frequencies of mutations in patients with signs of hereditary cancer were: 8.3%
      in group of young patients (under 40 years), 20.0% in patients with bilateral
      cancer and 5.7% in patients with family history of breast or ovarian cancers. We
      tested 516 BC patients residing on the territory of the Buryat-Aginsky district,
      Republics of Tyva and Altai. Out of them, there were 197 patients among the
      indigenous population (buryats, tuvinians, altaians), and 319 patients among
      newcomers (Slavic ethnics). Mutations BRCA1 5382insC were detected only in women
      from Slavic ethnic groups. The frequency of BRCA1 5382insC mutation was 6% in the
      group where family history was excluded and 14% in the group of patients with
      characteristics of family cancer. Allele BRCA1 5382insC was not found in
      indigenous breast cancer patients, although 59 patients had signs of hereditary
      cancer. In women from Slavic ethnic group, the BRCA1 185delAG, BRCA1 4153delAG
      and BRCA1 T300G mutations were detected in 9.1% of cases and were not found in
      patients among the indigenous population. CONCLUSION: studies of mutations in the
      BRCA1 gene in breast cancer patients from Siberia confirmed data on the high
      frequency of "founder mutation" BRCA1 5382insC in Slavic population and indicate
      the advisability of further studies to identify the genes responsible for the
      occurrence of hereditary breast cancer in the indigenous population.

PMID- 25971131
TI  - [The effect of different types of sports and athletes' age on the pathological
      changes of the musculoskeletal system].
AB  - OBJECTIVE: Our aim was to determine the most common musculoskeletal diseases,
      depending on the type of sports and athletes' age. METHODS: The results of
      examination of 976 athletes aged from 16 to 42 years (average age - 28,9+/-2,3)
      with musculoskeletal diseases were analyzed. Medical diagnostic procedures
      included clinical, laboratory, instrumental (radiography, magnetic resonance
      imaging, ultrasound) investigations and functional testing (goniometry, manual
      muscle testing). RESULTS: Majority of patients were diagnosed to have diseases of
      the knee (17.9%) and ankle joints (11.3%), the heel bone (12.9%), Achilles tendon
      (10.2%), post-traumatic musculoskeletal diseases (16.2%), degenerative-dystrophic
      diseases of the spine (12.8%). In the young age group (16 to 20 years) post
      traumatic disorders were most common. In the middle-age group (21 to 30 years)
      along with post-traumatic disorders diseases of the knee frequently occurred. For
      athletes over 30 years old, along with diseases of the knee spinal diseases were
      found to occur 2-3 times more frequently in comparison with other age groups.
      Injuries which are more common for different types of sports were identified:
      acute traumas - competitive sports, diseases of the calcaneus - sports with
      running and jumping (athletics, volleyball, soccer), disease of ankle joints -
      sport with sharp change in movement direction (hockey, figure skating), disease
      of the knee - sports with high load of the knee joint (figure skating,
      gymnastics, volleyball, diseases of bones and joints of the upper extremity -
      tennis, disease of spine - weightlifting. CONCLUSION: pathological changes in the
      musculoskeletal system depend on the type of sports and the age of athletes. The
      combination of age and risk factors associated with type of sport increases the
      possibility of development of these diseases of the musculoskeletal system.

PMID- 25971132
TI  - [Metabolic adaptation resources of organism to studying at medical university
      students in European North].
AB  - BACKGROUND: A student studying is accompanied with psychoemotional stress that
      requires functional changes in metabolic systems. A blood leucocytes enzyme
      activity indexes that provides an adaptation are the indicators of energy
      metabolism. OBJECTIVE: The aim of investigation is to determine the features and
      role of metabolic adaptive changes in the white blood cells of the students in
      European North during educational process. METHODS: In the course of year, third
      course general practitioner faculty students of medical university were
      investigated seven times (before and after autumn semester, after winter
      examination period, after summer examination time and during a summer vacation).
      In blood leucocytes of all the examined patients indicators of enzymes activity
      of dehydrogenases were detected - succinate dehydrogenase (SDG) and glutamate
      dehydrogenase (GDG), as well as hydrolytic enzymes - acid phosphatase and
      alkaline phosphatase. RESULTS: During the year different changes of blood
      leucocytes enzyme activity were detected depending on the intensity of training
      load; a most higher SDG and GDG activity were detected in winter time, after
      examination period as well as after spring semester; an acid phosphatase occurred
      in the autumn semester but alkaline phosphatase increased in all examination
      times. CONCLUSION: An enzyme activity changes have a phase character and are
      accompanied by a coherent, mutual interaction that depends on educational process
      specifics and examinations. This changes lead to adequacy of adaptation response.

PMID- 25971133
TI  - [Radionuclide imaging in the evaluation of the functional state of the
      transplanted kidney in the post-transplant period].
AB  - OBJECTIVE: The aim of our clinical study was to evaluate the possibility of
      diagnosis of postrenal-transplantation complications in recipients using dynamic
      scintigraphy basing on temporaly parameters standard zones of interest and
      medullay zone of renal transplantat comparing the results with the histological
      findings. METHODS: We determined time of maximum and one-half maximal activity of
      radiopharmaceutical medication in renal transplantat, parenchyma and medullary
      zone the graft. According to pathological diagnosis, patients were categorized
      into three groups: first - normals (n =32), second - acute rejection (n =43),
      third - chronic nephropathy (n =43). RESULTS: In this study 118 patients aged 21
      60 (38.4+/-9,8) years were included who underwent dynamic renal scintigraphy and
      biopsy renal transplantat. The time of maximum activity radiopharmlaceuticals
      parenchyma the graft in patients in first group - 3.24+/-0.54 min, second -
      6.61+/-3.28 min, third - 6.21+/-4.17 mnin (p <0,001). The time of maximum
      activity radiopharmaceuticals medullary zone the graft in patients in first group
      - 3.95+/-0.95 ,min, second - 8.94+/-5.23 min (p <0,001), third - 7.29+/-4.16min
      (p <0,01). The time of maximum activity radiopharmaceutical the whole graft in
      patients in first group - 3.87+/-0.62 mi, second - 7.4+/-3.82 min (p <0,001),
      third - 8.03+/-4.28 min (p <0,01). The time one-half maximal activity
      radiopharmaceuticals parenchyma the graft in first group - 10.4+/-2.95 min,
      second - 37.09+/-3.89 min (p <0,001), third - 29.67+/-3.1 min (p <0,005). The
      time one-half maximal activity radiopharmaceuticals medullary zone the graft in
      first group - 11.71-5.93 min, second - 79.34+/-9.81 min (p <0,001), third -
      29.67+/-3.95 min (p <0,005). The time one-half maximal activity
      radiopharmaceuticals the whole graft in first group - 12.31+/-3.91 min, second -
      53.29+/-8.22 min, third - 52.71+/-7.86 mil (p <0,001). Anderson-Bahadur distance:
      T1/2 medullary zone the graft most significant between first and second groups
      patients (17.43), gives maximum index value at chronic nephropathy (-9.07), at
      differentiation between acute rejection and chronic nephropathy (8.48). Estimate
      of the area under the ROC indicate most infomative time of maximum accumulation
      of the radiopharmaceutical of the whole graft (SROC =0.907) in acute rejection
      and Tmax parenchyma the renal transplantat (SRoc =0.847) in patients with chronic
      nephropathy the graft. Sensitivity and specificity renal scintigraphy parameters
      of diagnosing on postrenal transplantation complications amounted 71.43-98.7% and
      67.7-96.43% respectively. CONCLUSION: Renal scintigraphy is an additional test
      for early detection on postrenal transplantation complications and correct
      tactics conducting recipients. The parameters of kinetics of nephrotropic
      radiopharmaceuticals provide diagnosis of acute rejection and chronic nephropathy
      the graft. Inclusion of radionuclide diagnostics to monitor the state renal
      transplantat optimizes approach to bioosies graft.

PMID- 25971134
TI  - [Experimental model of ocular ischemic diseases].
AB  - The review presents the most common methods of modeling of retinal ischemia in
      vitro (chemical ischemia with iodoacetic acid, incubation of the retinal pigment
      epithelium cells with oligomycin, deprivation of oxygen and glucose) and in vivo
      (a model with increased intraocular pressure, cerebral artery occlusion, chronic
      ligation of the carotid arteries, photocoagulation of the retinal vessels,
      occlusion of the central retinal artery, endothelin-1 administration). Modeling
      ischemic injury in rats is the most frequently used method in studies, because
      the blood supply of their eyes is similar to blood flow in the human eyes. Each
      method has its own advantages and disadvantages. Application of methods depends
      on the purpose of the experimental study. Currently model of ocular ischemic
      disease can be obtained easily by injecting vasoconstrictive drug endothelin-1.
      It is the most widely used method of high intraocular pressure induced ocular
      ischemic damage similar to glaucoma, occlusion of central retinal artery or
      ophthalmic artery in human. The development of experimental models of ocular
      ischemic diseases and detailed investigation of mechanisms of impairment of
      microcirculation are useful for improve the efficiency of diagnostic and
      treatment of ischemic diseases of retina and optic nerve.

PMID- 25971135
TI  - [Changes in functional activity of neutrophils in peripheral blood of patients
      with renal cell cancer in the course of the disease].
AB  - OBJECTIVE: Research purpose was to study phagocytic activity and a oxygen
      depended metabolism of blood neutrophils (NF) at patients with a renal cell
      carcinoma in dynamics - before operation and after surgical treatment. METHODs;
      Patients with a locally invasive renal cell carcinoma (T3N0M0) were put under
      observation before surgical treatment (n =84) and in 10 days after a radical
      nephrectomy (n =54) at the age of 45-55 years. The 56 conditionally healthy
      donors combine into the control group. Indicators of functional activity, the
      spontaneous and induced lyuminol- and lyutsigenin-dependent chemiluminescence
      (CHL) NF of pedipheral blood was studied. RESULTS: During the period before
      operation time of an exit to a maximum of spontaneous and stimulated lyuminol
      dependent HL is slowed down (p <0.004 and p <0.006 respectively); indicators of
      the area of lyutsigenin-dependent HL NF of blood concerning indicators of control
      group are increased (p <0.01 for spontaneous, p <0.004 for the reaction induced
      by lyutsigenin). In 10 days after surgical treatment the quantity of active
      ingestion rate decreased (p <0.017 in the test with S. epidermidis, p <0.036 for
      test with latex); time of an exit to a maximum of spontaneous and stimulated
      lyuminol-dependent remained increased (p <0.006 and p <0.008 respectively) in
      comparison with indicators of healthy donors. The amount of an index of
      activation of lyuminol-dependent as in comparison with control (p <0.037), and
      relative to the period before operation increased (p <0.048). The area of
      spontaneous lyutsigenin-dependent HL NF of blood relative to indicators of
      control group was still increased (p <0.011), decrease in this parameter in
      comparison with amount of group before operation was however registered (p
      <0.004). CONCLUSION: At patients with renal cell carcinoma in 10 days after
      surgical treatment of NF of blood were characterized by the strengthened
      production of high-energy oxidizers and the reduced phagocytic activity that
      testifies to a functional and metabolic imbalance.

PMID- 25971136
TI  - [Pathophysiological aspects of wound healing in normal and diabetic foot].
AB  - The main cause of long-term healing of ulcers in patients with diabetic foot is
      considered to be direct mechanical damage when walking due to reduced sensitivity
      to due to neuropathy, hyperglycemia, infection and peripheral artery disease.
      These factors determine the standard approaches to the treatment of diabeticfoot,
      which include: offloading, glycemic control, debridement of ulcers, antibiotic
      therapy and revascularization. Recently, however, disturbances in the healing
      process of the skin in diabetes recognized an additional factor affecting the
      timing of healing patients with diabetic foot. Improved understanding and
      correction of cellular, molecular and biochemical abnormalities in chronic wound
      in combination with standard of care for affords new ground for solving the
      problem of ulcer healing in diabetes.

PMID- 25971137
TI  - [Topical issues of biological safety under current conditions. Part 3. Scientific
      provision for the national regulation of the biological safety framework in its
      broad interpretation].
AB  - Consequent of investigation concerned with biological safety (BS) framework
      development in its broad interpretation, reflected in the Russian Federation
      State Acts, identified have been conceptual entity parameters of the up-to-date
      broad interpretation of BS, which have formed a part of the developed by the
      authors system for surveillance (prophylaxis, localization, indication,
      identification, and diagnostics) and control (prophylaxis, localization, and
      response/elimination) over the emergency situations of biological (sanitary
      epidemiological) character. The System functionality is activated through
      supplying the content with information data which are concerned with monitoring
      and control of specific internal and external threats in the sphere of BS
      provision fixed in the Supplement 2 of the International Health Regulations (IHR,
      2005), and with the previously characterized nomenclature of hazardous biological
      factors. The system is designed as a network-based research-and-practice tool for
      evaluation of the situation in the sphere of BS provision, as well as assessment
      of efficacy of management decision making as regards BS control and proper State
      policy implementation. Most of the system elements either directly or indirectly
      relate to the scope of activities conducted by Federal Service for Surveillance
      in the Sphere of Consumers Rights Protection and Human Welfare, being substantial
      argument for allocating coordination functions in the sphere of BS provision to
      this government agency and consistent with its function as the State Coordinator
      on IHR (2005). The data collected serve as materials to Draft Federal Law
      "Concerning biological safety provision of the population".

PMID- 25971138
TI  - [The combined use of bisphosphonates and strontium ranelate with
      osseosubstituting materials].
AB  - In review the possibility of biomaterials osseointegration improvement with help
      of bisphosphonates or strontium ranelate is discussed. For this purpose, they are
      added to hydroxyapatite used for implants coating, or are included as a component
      of bulk calcium phosphate materials. Strontium is employed as a compound of
      biodegradable metal alloys, also. Combined use of carrier (implant) with
      bisphosphonates or strontium ranelate promotes controlling local delivery of
      pharmaceutical molecules into lesion, enhances the therapy efficiency, and
      decreases a dose and systemic toxicity of the drugs. Bisphosphonates and
      strontium ranelate increase the mass, a count and thickness of bone trabeculas,
      improve the bone biomechanical properties in the place of implants fixation, and
      diminish the bone fracture risk. Main studies are devoted to pharmacologic
      mechanisms of implants osseointegration improvement. Bisphosphonates as
      isoprenoid lipids chemical analogues diminish by concurrent principle the
      osteoclastsfarnesylpyrophosphate synthase activity and inhibit the prenylation.
      Unprenylated small GTPases don't fasten onto osteoclasts membrane that weakens
      cellular resorptive activity and accelerates their apoptosis. Strontium ranelate
      enhances osteoblasts replicative activity and suppresses their apoptosis, also
      retards osteoclasts resorptive function and accelerates their apoptosis. Its
      effects are conditioned by activating Wnt-signaling pathway by means of calcium
      sensing receptor and by changing the RANKL/RANK/OPG system.

PMID- 25971139
TI  - [Valerii Aleksandrovich Kaptsov].

PMID- 25971140
TI  - [Andpei Mikhailovich Stochik].

PMID- 25971141
TI  - [eHealth made in Germany].

PMID- 25971142
TI  - [Mental disorders and their impact on mortality and morbidity (II)].

PMID- 25971143
TI  - [Complex regional pain syndrome (CRPS) - difficulties in diagnostics, therapy and
      assessment].
AB  - CRPS is still widely unknown among physicians. However, surgeons and GPs should
      know the diagnostic criteria and the modern therapeutic approaches in order to
      start early therapy according to recent medical guidelines. Pain specialists and/
      or neurologists should be involved because of their clinical and neuroanatomic
      knowledge. First-line therapy comprises neither extensive instrumental diagnostic
      procedures nor invasive treatments, which - in some cases - could even worsen the
      disease. The key point is a variety of specific physiotherapeutic techniques. The
      prognosis is not as poor as many physicians believe.

PMID- 25971144
TI  - [Medical certification of chronic fatigue syndrome].
AB  - Chronic fatigue or chronic fatigue syndrome (CFS) is not a new disease, yet in
      recent years it has become increasingly important as an evaluation problem. It
      coincides with the well-known clinical picture of neurasthenia, shows extensive
      overlap with symptoms of depression and, finally, to the current concept of
      "burnout". Regarding the etiology there is fierce controversy between the
      representatives of a somatic and a psychological etiology. As reviewers you will
      be guided by the assessment criteria for somatoform disorders, especially because
      objectified findings are lacking. CFS can be independently encoded as
      neurological diagnosis G 93.3 according to ICD-10, although never objectified
      neurological deficits were detected, as well as neurasthenia F 48.0 or
      accompanying physical symptoms as somatization disorder F 45.0.

PMID- 25971145
TI  - [Difficulties in the assessment of trauma-related disorders].
AB  - Assessment of trauma disorders is becoming increasingly important. A major
      problem here is that trauma disorders are extremely heterogeneous. Moreover, they
      are often associated with comorbid disorders, such as borderline personality
      disorder. The valid diagnostic systems ICD-10 and DSM-5 poorly represent trauma
      disorders. The so-called complex post-traumatic stress disorder or DESNOS
      (disorders of extreme stress not otherwise specified) are listed .in either of
      the ICD-10 or DSM-5. The distinctiveness is not generally scientifically
      accepted. In addition, the assessment of trauma disorders is complicated because
      there are often multiple traumas of varying degrees of severity.

PMID- 25971146
TI  - [Insurance medical consultation in private health insurance - which insurance
      medical questions are put to the medical consultant?].
AB  - BACKGROUND: This study deals with the task areas of the medical consultant in
      private health insurance. Although insurance medical consultation for the
      insurance business originated in the 19th century, the tasks and competencies of
      the medical consultants are still mostly unknown. METHODS: This study is a
      complete inventory count of all insurance medical consultation requests for the
      year 2013. All of the 5493 insurance medical consultation requests have been
      evaluated. RESULTS AND DISCUSSION: Most of the consultation requests concern the
      medical necessity for medical drugs, followed by the medical consultation of
      alternative medicine and the classification of cure and rehabilitation measures
      of hospital medical treatments. The need for insurance medical consultation on
      lifestyle drugs, cosmetic operations and artificial insemination has increased
      significantly in the past 10 years. Since 2009, moreover, the need for medical
      consultation on the subject of "Ruhensleistungen" with regard to non-payers and
      "Notlagentarif" has strongly increased.

PMID- 25971147
TI  - [Risks and complications of alternative medical treatments].

PMID- 25971148
TI  - [Alternative medicine treatment of irritable bowel syndrome -- what are the
      guidelines?].

PMID- 25971149
TI  - [Shoulder surgery in beautiful Switzerland more than eight times as expensive as
      in Germany].

PMID- 25971150
TI  - [Return to work -- concept of private health insurance].

PMID- 25971152
TI  - Correction to Optically abrupt localized surface plasmon resonances in Si
      nanowires by mitigation of carrier density gradients.

PMID- 25971151
TI  - [Prognosis for rheumatoid arthritis].

PMID- 25971153
TI  - Characterization and immunomodulatory activities of polysaccharides from
      Spirogyra neglecta (Hassall) Kutzing.
AB  - Sulfated polysaccharides (SP) isolated from freshwater green algae, Spirogyra
      neglecta (Hassall) Kutzing, and fractionated SPs were examined to investigate
      their molecular characteristics and immunomodulatory activity. The crude and
      fractionated SPs (F1, F2, and F3) consisted mostly of carbohydrates (68.5-85.3%),
      uronic acids (3.2-4.9%), and sulfates (2.2-12.2%) with various amounts of
      proteins (2.6-17.1%). D-galactose (23.5-27.3%), D-glucose (11.5-24.8%), L-fucose
      (19.0-26.7%), and L-rhamnose (16.4-18.3%) were the major monosaccharide units of
      these SPs with different levels of L-arabinose (3.0-9.4%), D-xylose (4.6-9.8%),
      and D-mannose (0.4-2.3%). The SPs contained two sub-fractions with molecular
      weights (Mw) ranging from 164 * 10(3) to 1460 * 10(3) g/mol. The crude and
      fractionated SPs strongly stimulated murine macrophages, producing considerable
      amounts of nitric oxide and various cytokines via up-regulation of their mRNA
      expression by activation of nuclear factor-kappa B and mitogen-activated protein
      kinases pathways. The main backbone of the most immunoenhancing SP was (1->3)-L
      Fucopyranoside, (1->4,6)-D-Glucopyranoside, and (1->4)-D-Galactopyranoside.

PMID- 25971154
TI  - Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus
      Task Force recommendations for evaluation and management.
AB  - OBJECTIVE: To develop disease-specific recommendations for the diagnosis and
      management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss
      syndrome) (EGPA). METHODS: The EGPA Consensus Task Force experts comprised 8
      pulmonologists, 6 internists, 4 rheumatologists, 3 nephrologists, 1 pathologist
      and 1 allergist from 5 European countries and the USA. Using a modified Delphi
      process, a list of 40 questions was elaborated by 2 members and sent to all
      participants prior to the meeting. Concurrently, an extensive literature search
      was undertaken with publications assigned with a level of evidence according to
      accepted criteria. Drafts of the recommendations were circulated for review to
      all members until final consensus was reached. RESULTS: Twenty-two
      recommendations concerning the diagnosis, initial evaluation, treatment and
      monitoring of EGPA patients were established. The relevant published information
      on EGPA, antineutrophil-cytoplasm antibody-associated vasculitides,
      hypereosinophilic syndromes and eosinophilic asthma supporting these
      recommendations was also reviewed. DISCUSSION: These recommendations aim to give
      physicians tools for effective and individual management of EGPA patients, and to
      provide guidance for further targeted research.

PMID- 25971155
TI  - Morphological differences in innervation between mucous glands and serous glands:
      a quantitative histological study using the sublingual glands of elderly humans.
AB  - CONCLUSION: In the sublingual gland, the serous lobule usually carried a higher
      density of NSE-positive nerve elements than the mucous lobule, whereas the mucous
      acinus in the mucous lobule was larger than the serous acinus in the serous
      lobule. OBJECTIVES: To demonstrate quantitative differences in nerve elements
      between the mucous and serous lobules of sublingual glands. METHODS: This study
      investigated using specimens from 14 donated cadavers (mean age = 78 years).
      Since immunohistochemistry for neuron-specific enolase (NSE) stains all nerves in
      addition to other mesenchymal cells possibly of nerve origin, the present
      quantitative evaluation was based on NSE-positive areas per visual field under a
      *20 objective lens (0.6 * 0.45 mm when printed). RESULTS: In mucous lobules, the
      areas occupied by NSE-positive nerve elements ranged from 5798-16,541 MUm(2)
      (mean +/- SD = 9280 +/- 2584 MUm(2)). In contrast, the corresponding areas in
      serous lobules ranged from 7853-23,540 MUm(2) (mean +/- SD = 13,520 +/- 4351
      MUm(2)). The difference in NSE-positive areas was statistically significant (p =
      0.0022). However, the mucous acinus in the mucous lobule was 2-times larger than
      the serous acinus in the serous lobule (2474 +/- 1477 MUm(2) vs 1119 +/- 632
      MUm(2)).

PMID- 25971156
TI  - Comparison of BKV quantification using a single automated nucleic acid extraction
      platform and 3 real-time PCR assays.
AB  - Monitoring peripheral blood for evidence of BK viremia through quantitative real
      time PCR testing is an important management tool that allows for interventions
      that prevent nephropathy in renal allograft patients. This study compared the
      performance of 3 different real-time PCR assays for BKV quantification including
      2 noncommercial tests (a historical assay "PEP" and 1 with improved genotypic
      inclusivity "V3T3") and 1 using commercial reagents (Qiagen/artus, "artus") after
      nucleic acid extraction of plasma with a single automated instrument
      (QIAsymphony). The measurable ranges (log10 copies/mL) were 2.7 to at least 8.0
      for PEP and 2.0 to at least 8.0 for artus and V3T3 assays. Limits of detection
      (copies/mL) were 189, 56, and 28 for PEP, V3T3, and artus, respectively.
      Correlation experiments demonstrated linearity with original quantification
      results, although values obtained for the PEP assay were generally lower than
      those obtained for the V3T3 or artus assay across the measuring range. V3T3 and
      artus values were more closely related, although artus values were generally
      lower. The 3 assays returned different values from clinical plasma samples,
      likely due in part to variances in calibration. Low BKV concentrations were
      quantifiable by V3T3 and artus assays in plasmas that were previously deemed
      negative by PEP. These data underscore the need for monitoring with a single test
      to enable appropriate management decisions, and they suggest that an
      international preparation would be useful in harmonizing quantification of BKV
      viremia. 

PMID- 25971157
TI  - Analytical study of dispersion relations for shear horizontal wave propagation in
      plates with periodic stubs.
AB  - The coupled mode theory with coupling of diffraction modes and waveguide modes is
      usually used on the calculations of transmission and reflection coefficients for
      electromagnetic waves traveling through periodic sub-wavelength structures. In
      this paper, I extend this method to derive analytical solutions of high-order
      dispersion relations for shear horizontal (SH) wave propagation in elastic plates
      with periodic stubs. In the long wavelength regime, the explicit expression is
      obtained by this theory and derived specially by employing an effective medium.
      This indicates that the periodical stubs are equivalent to an effective
      homogenous layer in the long wavelength. Notably, in the short wavelength regime,
      high-order diffraction modes in the plate and high-order waveguide modes in the
      stubs are considered with modes coupling to compute the band structures.
      Numerical results of the coupled mode theory fit pretty well with the results of
      the finite element method (FEM). In addition, the band structures' evolution with
      the height of the stubs and the thickness of the plate shows clearly that the
      method can predict well the Bragg band gaps, locally resonant band gaps and high
      order symmetric and anti-symmetric thickness-twist modes for the periodically
      structured plates. 

PMID- 25971158
TI  - Investigation of a rotary ultrasonic motor using a longitudinal vibrator and
      spiral fin rotor.
AB  - A Langevin transducer can provide longitudinal vibration with larger amplitude
      while also possessing a greater fatigue life than other types of piezoelectric
      vibrators. A novel rotary Ultrasonic Motor (USM) was proposed based on the use of
      a longitudinal transducer (acting as the stator) and a spiral fin rotor: the
      front cover of the Langevin transducer was designed as a double-layer cup-shaped
      structure, with the rotor sustained by the inner-layer, and the bearing cover
      fixed to the outer-layer; the rotor consisted of a shaft and spiral fins which
      acted as the elastic coupler. It is different from a traditional traveling USM,
      because the stator provides longitudinal vibration and the rotor generates the
      elliptical motion. This paper analyzed the motion locus equation of the fin
      contact points. Additionally, a theoretical analysis was performed in regards to
      the mechanism and the motor's rotor motion characteristics, which demonstrates
      the relationships among the motor's driving force, the torque, the revolution
      speed, and the motor structure parameters. A motor prototype has been
      manufactured and surveyed to demonstrate the motor performance. The relationships
      between the amplitude and the preload on the rotor, the free revolution speed,
      and the torque of the motor have also been studied. 

PMID- 25971159
TI  - Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis in vitro.
AB  - Toxic and harmful factors co-exist in the environment; these factors often
      interact to induce combined toxicity, which is the main focus of toxicological
      research. Furthermore, a large number of studies have shown that aluminum (Al)
      and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to
      cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air,
      water, food, and even medicine, the combined effects of these agents in humans
      must be examined. The present study examines the ability of Al and BaP co
      exposure to intensify neuronal apoptosis. The primary neurons of newborn rats
      were cultured for 5 days, and cells from the same batch that were growing well
      were selected and assigned to the blank control group, the solvent control group
      (DMSO+S9+maltol), BaP groups (10, 40 MUmol/L), Al (mal)3 groups (50, 100, 400
      MUmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3.
      The cell viabilities indicated that 10 MUM BaP or 50 MUM Al (mal)3 was mildly
      toxic, and we selected 10 MUM BaP+50 MUM Al (mal)3 for subsequent co-exposure
      experiments. The morphological characteristics of cell apoptosis were much more
      obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed
      cells, as observed with a transmission electron microscope and a fluorescence
      inverted microscope. The apoptotic rates and caspase-3 activity quantitatively
      significantly differed between the co-exposure and Al-exposure groups, while the
      BaP-exposure group did not significantly differ from the control group. These
      results indicate that Al and BaP co-exposure exert synergistic effects on
      neuronal cell apoptosis. 

PMID- 25971160
TI  - Cell line development for biomanufacturing processes: recent advances and an
      outlook.
AB  - At the core of a biomanufacturing process for recombinant proteins is the
      production cell line. It influences the productivity and product quality. Its
      characteristics also dictate process development, as the process is optimized to
      complement the producing cell to achieve the target productivity and quality.
      Advances in the past decade, from vector design to cell line screening, have
      greatly expanded our capability to attain producing cell lines with certain
      desired traits. Increasing availability of genomic and transcriptomic resources
      for industrially important cell lines coupled with advances in genome editing
      technology have opened new avenues for cell line development. These developments
      are poised to help biosimilar manufacturing, which requires targeting pre-defined
      product quality attributes, e.g., glycoform, to match the innovator's range. This
      review summarizes recent advances and discusses future possibilities in this
      area. 

PMID- 25971161
TI  - Reviewers: The unsung heroes of publication.

PMID- 25971162
TI  - Primary vitreoretinal lymphoma.
AB  - Primary vitreoretinal lymphoma (PVRL) is an uncommon, but potentially fatal
      intraocular malignancy, which may occur with or without primary central nervous
      system lymphoma (PCNSL). Considered to be a subset of PCNSL, it is mostly of
      diffuse large B-cell type. The diagnosis of PVRL poses a challenge not only to
      the clinician, but also to the pathologist. Despite aggressive treatment with
      chemotherapy and/or radiotherapy, relapses or CNS involvement are common. 

PMID- 25971164
TI  - Options for management of intra ocular tumors.
AB  - The management of intra ocular tumors has undergone a sea change from the era of
      enucleation or external beam radiation. With the advent of new chemotherapy
      protocols, globe and vision salvage have become possible in a majority of cases
      of retinoblastoma. This article is an overview of the various modalities
      available for the management of intra ocular tumors and their indications.
      Chemotherapy has been covered elsewhere in this series of articles on ocular
      oncology. Photocoagulation and cryopexy are easily administered modalities of
      treatment for small tumors and totally within the ophthalmologist's domain.
      Slightly larger tumors are treatable with brachytherapy. The susceptibility of
      the tumors to chemotherapy and radiation decide the choice of treatment and the
      dosage. Management of intra ocular tumors very often needs a multidisciplinary
      approach including ophthalmologist, oncologist, radiation physicist, and
      radiotherapist. 

PMID- 25971163
TI  - Tumors of the ocular surface: A review.
AB  - Tumors of the Ocular Surface clinically manifest with a very wide spectrum and
      include several forms of epithelial, stromal, caruncular, and secondary tumors.
      As a group, these tumors are seen commonly in the clinical practice of a
      comprehensive ophthalmologist, cornea specialist, and an ocular oncologist. This
      review is aimed to discuss the common tumors of the ocular surface and emphasize
      on their clinical diagnosis and appropriate management. 

PMID- 25971165
TI  - Experimental autoimmune uveitis and other animal models of uveitis: An update.
AB  - Over the past several decades, animal models of autoimmune uveitis directed at
      eye-specific antigens (Ags) have been developed. These have allowed researchers
      to understand the basic mechanisms that lead to these diseases and also recently
      helped the researchers in translational research for therapeutic interventions.
      Experimental autoimmune uveitis (EAU) is an animal disease model of human
      endogenous uveitis and can be induced in susceptible animals by immunization with
      retinal Ags. Ever since the first description of EAU in mice in 1988, several
      animal models of uveitis has been described by researchers. Disease-specific
      model for cytomegalovirus retinitis and tubercular uveitis has evolved our
      understanding of these complex entities. Endotoxin induced uveitis is another
      useful model for anterior uveitis, which is not an autoimmune process and is
      triggered by injection of bacterial endotoxin (lipopolysaccharides) resulting in
      a rapid short lasting uveitis. The current article will give an insight into the
      various EAU animal models and their current implications in translational
      research. The article will also highlight the different grading systems for EAU
      in the animal model. 

PMID- 25971166
TI  - Retinoblastoma genetics in India: From research to implementation.
AB  - Retinoblastoma is the prototypic genetic cancer. India carries the biggest burden
      of retinoblastoma globally, with an estimated 1500 new cases annually. Recent
      advances in retinoblastoma genetics are reviewed, focusing specifically on
      information with clinical significance to patients. The Indian literature on
      retinoblastoma clinical genetics is also highlighted, with a comment on
      challenges and future directions. The review concludes with recommendations to
      help clinicians implement and translate retinoblastoma genetics to their
      practice. 

PMID- 25971167
TI  - Development of ocular hypertension secondary to tamponade with light versus heavy
      silicone oil: A systematic review.
AB  - AIM: The intraocular silicone oil (SO) tamponades used in the treatment of
      retinal detachment (RD) have been associated with a difference ocular
      hypertension (OH) rate. To clarify, if this complication was associated to use of
      standard SO (SSO) versus heavy SO (HSO), we performed a systematic review and
      meta-analysis of comparative study between two kind of SO (standard or light vs.
      heavy) for the treatment of RD and macular hole, without restriction to study
      design. MATERIALS AND METHODS: The methodological quality of two randomized
      clinical trials (RCTs) were evaluated using the criteria given in the Cochrane
      Handbook for Systematic Reviews of Intervention, while three non-RCTs were
      assessed with the Newcastle-Ottawa Scale and Strengthening the Reporting of
      Observational Studies in Epidemiology checklists. We calculated Mantel-Haenszel
      risk ratio (RR) with 95% confidence intervals (95% CIs). The primary outcome was
      the rate of patients with OH treated with SSO compared to HSO. RESULTS: There
      were a higher number of rates of OH in HSO compared to SSO. This difference was
      statistically significant with the fixed effect model (Mantel-Haenszel RR; 1.55;
      95% CI, 1.06-2.28; P = 0.02) while there was not significative difference with
      the random effect model (Mantel-Haenszel RR; 1.51; 95% CI, 0.98-2.33; P = 0.06).
      CONCLUSION: We noted a trend that points out a higher OH rate in HSO group
      compared to SSO, but this finding, due to the small size and variable design of
      studies, needs to be confirmed in well-designed and large size RCTs.

PMID- 25971168
TI  - Keratoglobus: An experience at a tertiary eye care center in India.
AB  - CONTEXT: This study was carried out as a part of an internal audit and is the
      largest series of patients having keratoglobus, published in the literature. Poor
      visual acuity of the patients indicates the blinding nature of the disease. AIMS:
      We report our experience with patients having keratoglobus at a tertiary eye care
      center in India. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS:
      We analyzed adults and pediatric patients (<16 years) with keratoglobus, seen
      during 2008-2012. The age, gender, consanguinity, presenting ocular signs, ocular
      and systemic associations, visual acuity, corneal topography, and surgeries were
      documented. RESULTS: Forty-eight patients (mean age 22 +/- 15 years, 31 males)
      having keratoglobus were analyzed. 21 patients (42 eyes) were <16 years. Twelve
      eyes (16 events) had positive history of trauma. The presenting clinical signs
      were corneal scars/scars of tear repair (15 eyes), hydrops, healed and acute (14
      eyes) and corneal or globe rupture (9 eyes). Best-corrected visual acuity was
      >20/40 in 6/42 (14.3%) pediatric eyes and 15/53 (28.30%) adults. Visual acuity
      ranging from counting of fingers to no light perception was noted in 20/53
      (37.74%) adults and 21/42 (50%) pediatric patients; 13/20 (65%) with blue sclera
      and 8/22 eyes (36.37%) without blue sclera. Vernal keratoconjunctivitis was
      present in one pediatric patient. Choroidal osteoma, retinitis pigmentosa, and
      retinal detachment were present in adults. Surgeries performed were corneal tear
      repair (5 eyes), tissue adhesive application (2 eyes), descematopexy (4 eyes) and
      penetrating keratoplasty (PK - 8 eyes: Three had post-PK glaucoma, graft failure
      one eye, 4 patients wore scleral lens - prosthetic replacement of the ocular
      surface ecosystem). CONCLUSIONS: About 50% of pediatric eyes (65% having blue
      sclera) had no functional vision. Trivial trauma was responsible for corneal
      rupture indicating need for protective glasses. About 50% patients had post-PK
      glaucoma though grafts were clear.

PMID- 25971169
TI  - Evaluation of choroidal thickness via enhanced depth-imaging optical coherence
      tomography in patients with systemic hypertension.
AB  - PURPOSE: The purpose was to evaluate choroidal thickness via spectral domain
      optical coherence tomography (SD-OCT) and to compare the data with those of 24-h
      blood pressure monitoring, elastic features of the aorta, and left ventricle
      systolic functions, in patients with systemic hypertension. MATERIALS AND
      METHODS: This was a case-control, cross-sectional prospective study. A total of
      116 patients with systemic hypertension, and 116 healthy controls over 45 years
      of age, were included. Subfoveal choroidal thickness (SFCT) was measured using a
      Heidelberg SD-OCT platform operating in the enhanced depth imaging mode. Patients
      were also subjected to 24-h ambulatory blood pressure monitoring (ABPM) and
      standard transthoracic echocardiography (STTE). Patients were divided into
      dippers and nondippers using ABPM data and those with or without left ventricular
      hypertrophy (LVH+ and LVH-) based on STTE data. The elastic parameters of the
      aorta, thus aortic strain (AoS), the beta index (BI), aortic distensibility
      (AoD), and the left ventricular mass index (LVMI), were calculated from STTE
      data. RESULTS: No significant difference in SFCT was evident between patients and
      controls (P <= 0.611). However, a significant negative correlation was evident
      between age and SFCT in both groups (r = -0.66/-0.56, P <= 0.00). No significant
      SFCT difference was evident between the dipper and nondipper groups (P <= 0.67),
      or the LVH (+) and LVH (-) groups (P <= 0.84). No significant correlation was
      evident between SFCT and any of AoS, BI, AoD, or LVMI. DISCUSSION: The choroid is
      affected by atrophic changes associated with aging. Even in the presence of
      comorbid risk factors including LVH and arterial stiffness, systemic hypertension
      did not affect SFCT.

PMID- 25971170
TI  - Investigation of the choroidal thickness in patients with hypothyroidism.
AB  - PURPOSE: The effect of hypothyroidism on the choroidal thickness (CT) was
      investigated in patients with subclinical hypothyroidism and overt
      hypothyroidism, and biochemically and clinically euthyroid patients receiving
      levothyroxine treatment. The patients were compared with healthy subjects.
      MATERIALS AND METHODS: One eye of 71 hypothyroid and 22 healthy subjects between
      20 and 40 years of age were included in this study. CT measurements were taken at
      the fovea and at 2 points that were 1500 MUm nasal and temporal to the fovea
      using spectral-domain optical coherence tomography. Independent sample t-test's
      and was used for statistical analysis of the data. RESULTS: The CT was
      significantly thicker in hypothyroid patients compared to healthy subjects (P
      values were 0.013 for subfoveal, 0.015 for temporal and 0.020 for nasal
      segments). The intraocular pressure (IOP) and body mass index (BMI) were also
      significantly higher in hypothyroid patients (P values were 0.021 and 0.003,
      respectively). There was not a statistically significant difference in the BMI
      and IOP measurements between healthy subjects and euthyroid patients (P > 0.05).
      However, there was a statistically significant difference in the subfoveal,
      temporal and nasal CT measurements between healthy subjects and euthyroid
      patients (P values were 0.006, 0.031 and 0.013, respectively). CONCLUSIONS: All
      subgroups of hypothyroid patients had thicker CT compared to healthy subjects.
      Euthyroid patients receiving levothyroxine treatment had lower IOP, BMI levels,
      and serum lipid levels than patients with subclinical hypothyroidism and overt
      hypothyroidism.

PMID- 25971171
TI  - Effect of bilateral superior oblique split lengthening on torsion.
AB  - INTRODUCTION: Superior oblique split lengthening (SOSL) is done for weakening of
      superior oblique. It corrects the superior oblique overaction (SOOA) and A
      pattern. Its effect on the torsion of the eye is not known. We present our data
      on the effect of this particular procedure on torsion. MATERIALS AND METHODS: We
      did a study of 16 patients (32 eyes) who underwent bilateral SOSL and compared
      the disc foveal angle (DFA) preoperatively and postoperatively. The split
      lengthening was done from 4 mm to 7 mm depending upon the overaction of superior
      oblique. RESULTS: The mean age was 15.3 +/- 8.4 years. Mean preoperative DFA in
      the right eye (RE) was -3.9 degrees  and in the left eye (LE) was -2.9 degrees .
      Mean postoperative DFA in RE was 0.2 degrees  and in LE was 0.9 degrees . The
      mean change in the DFA for RE was 4.1 degrees  +/- 1.3 degrees  and for LE was
      3.8 degrees  +/- 1.2 degrees . All the patients were aligned horizontally within
      6 prism diopter and no pattern and no diplopia postoperatively. The A pattern was
      corrected in all the patient postsurgery. For each mm of surgery, an improvement
      of 0.8 degrees  was seen in the DFA. CONCLUSION: We report the effect of SOSL on
      torsion. The SOSL reduces intorsion postsurgery and is, therefore, a valuable
      procedure in SOOA where both pattern and in torsion needs to be corrected.

PMID- 25971172
TI  - Visual impairment and blindness among the students of blind schools in Allahabad
      and its vicinity: A causal assessment.
AB  - BACKGROUND/AIMS: Information on eye diseases in blind school children in
      Allahabad is rare and sketchy. A cross-sectional study was performed to identify
      causes of blindness (BL) in blind school children with an aim to gather
      information on ocular morbidity in the blind schools in Allahabad and in its
      vicinity. STUDY DESIGN AND SETTING: A cross-sectional study was carried out in
      all the four blind schools in Allahabad and its vicinity. MATERIALS AND METHODS:
      The students in the blind schools visited were included in the study and informed
      consents from parents were obtained. Relevant ocular history and basic ocular
      examinations were carried out on the students of the blind schools. RESULTS: A
      total of 90 students were examined in four schools of the blind in Allahabad and
      in the vicinity. The main causes of severe visual impairment and BL in the better
      eye of students were microphthalmos (34.44%), corneal scar (22.23%), anophthalmos
      (14.45%), pseudophakia (6.67%), optic nerve atrophy (6.67%), buphthalmos/glaucoma
      (3.33%), cryptophthalmos (2.22%), staphyloma (2.22%), cataract (2.22%), retinal
      dystrophy (2.22%), aphakia (1.11%), coloboma (1.11%), retinal detachment (1.11%),
      etc. Of these, 22 (24.44%) students had preventable causes of BL and another 12
      (13.33%) students had treatable causes of BL. CONCLUSION: It was found that
      hereditary diseases, corneal scar, glaucoma and cataract were the prominent
      causes of BL among the students of blind schools. Almost 38% of the students had
      preventable or treatable causes, indicating the need of genetical counseling and
      focused intervention.

PMID- 25971173
TI  - Golden half ring sign for identification of pseudophacocele.
AB  - Dislocation of intraocular lens (IOL) is a serious complication of blunt ocular
      trauma in pseudophakic eyes. Here, a 72-year-old male patient with
      subconjunctival dislocation of an IOL (pseudophacocele) secondary to bull horn
      injury was reported. In this case report, a new sign named as "golden half ring
      sign" was described for easy identification and localization of subconjunctival
      dislocation of IOL in patient with open globe injury (surgical wound dehiscence)
      associated dense subconjunctival hemorrhage. 

PMID- 25971174
TI  - Multiple soft fibromas of the lid.
AB  - Fibromas are benign tumors that are composed of fibrous or connective tissue.
      They can grow in all organs, arising from mesenchymal tissue (a type of loose
      connective tissue). The term "fibroblastic" or "fibromatous" is used to describe
      tumors like the fibroma. This 69-year-old male presented to us with giant,
      multiple, very slowly progressive, painless, noninflammatory, soft, trans
      illuminant, pedunculated lid swellings with a two decade history. There were no
      other swellings on the body. He was clinically normal on systemic examination
      except for the immature cataracts in both eyes. The diagnosis was confirmed on
      histopathology. Simple excision removed all the soft fibromas virtually leaving
      no scar. A review of literature world-wide using Medline Plus/PubMed revealed
      this to be the only reported case of multiple giant soft fibromas of the lid. 

PMID- 25971175
TI  - Ascher's syndrome: A rare case report.
AB  - An 18-year-old Indian girl with upper lip deformity presented with on and off
      painless swelling of her both upper eyelids for 3 years. Clinical evaluation
      revealed bilateral blepharochalasis, narrowing of horizontal palpebral fissure,
      decreased outer intercanthal distance, iris coloboma, cleft soft palate, bifid
      uvula, sensorineural deafness and double upper lip. Clinical examination of the
      thyroid, thyroid hormone assay and ultrasonography revealed normal thyroid gland
      structure and function. Ascher's syndrome was diagnosed. To our knowledge, this
      is the first reported case of Ascher's syndrome associated with iris coloboma,
      heterochromia iridum, and narrowing of horizontal palpebral fissure and decreased
      outer intercanthal distance secondary to lengthening of lateral canthal ligament.

PMID- 25971176
TI  - Reliability of "Google" for obtaining medical information.
AB  - Internet is used by many patients to obtain relevant medical information. We
      assessed the impact of "Google" search on the knowledge of the parents whose ward
      suffered from squint. In 21 consecutive patients, the "Google" search improved
      the mean score of the correct answers from 47% to 62%. We found that "Google"
      search was useful and reliable source of information for the patients with
      regards to the disease etiopathogenesis and the problems caused by the disease.
      The internet-based information, however, was incomplete and not reliable with
      regards to the disease treatment. 

PMID- 25971177
TI  - Embolization of a deep orbital varix through endovascular route.
AB  - We report a case of the primary deep orbital venous varix treated by endovascular
      coil embolization procedure by transfemoral catheterization. This method of
      treatment has the advantage of image-guided localization of the pathology, real
      time management and confirmation of the success of the procedure in the sitting. 

PMID- 25971178
TI  - Ciliochoroidal effusion with persistent hypotony after trabectome surgery.
AB  - The trabectome is a novel form of ab interno trabeculectomy that ablates and
      remove the trabecular meshwork and the inner wall of Schlemm's canal and
      subsequently expose the natural drainage pathway (the collector channels) to
      aqueous humor. Complications associated with the trabectome are few and among
      them is transient hypotony. We report a case of a prolonged ciliochoroidal
      effusion with hypotony after ab interno trabeculectomy using the trabectome with
      cyclodialysis cleft detected by 80 MHz ultrasound biomicroscopy in a previously
      neither nonoperated nor traumatized eye. Transient hypotony has been reported
      after the trabectome surgery. Very few cases were associated with inadvertent
      intraoperative cyclodialysis, but there are no cases of prolonged hypotony with
      ciliochoroidal effusion with cyclodialysis. In our case, associated transient
      intraoperative and postoperative hypotony with a history of chronically high
      pressure along with the possible contribution of low-grade postoperative
      inflammation may have precipitated the ciliochoroidal effusion with prolonged
      hypotony associated with cyclodialysis. 

PMID- 25971179
TI  - Goat's eye integrated with a human cataractous lens: A training model for
      phacoemulsification.
AB  - A relatively simple and inexpensive technique to train surgeons in
      phacoemulsification using a goat's eye integrated with a human cataractous
      nucleus is described. The goat's eye is placed on a bed of cotton within the
      lumen of a cylindrical container. This is then mounted on a rectangular thermocol
      so that the limbus is presented at the surgical field. After making a clear
      corneal entry with a keratome, the trainer makes a 5-5.5 mm continuous
      curvilinear capsulorhexis in the anterior lens capsule, creates a crater of
      adequate depth in the cortex and inserts the human nucleus within this crater in
      the goat's capsular bag. The surgical wound is sutured, and the goat's eye is
      ready for training. Creating the capsulorhexis with precision and making the
      crater of adequate depth to snugly accommodate the human nucleus are the most
      important steps to prevent excessive wobbling of the nucleus while training. 

PMID- 25971180
TI  - One glasses too many: A case report of Benson's syndrome.
AB  - We report a case of Benson's Syndrome, a form of occipital Alzheimer's disease,
      with posterior cortical atrophy on magnetic resonance imaging, in a 62-year-old
      male, who presented with visual problems, ascribed to the eyes, and had even
      undergone cataract/intraocular lens surgery in the right eye; and change of
      glasses 21 times over the past 2 years, with no apparent benefit. This case is of
      interest both on account of its rarity, and to highlight its features since the
      diagnosis may be missed in an ophthalmological setting where such patient may go
      for first consult. 

PMID- 25971181
TI  - Anterior dislocation of an empty capsular bag in a pseudophakic eye: A rare case
      report.
AB  - Spontaneous intraocular lens (IOL) dislocation is uncommon in the absence of any
      ocular areas with zonular weakness or trauma. There have been no reports of
      spontaneous capsular bag dislocation into the anterior chamber without an IOL. We
      report a rare, interesting case of spontaneous capsular bag anterior dislocation,
      without an IOL, into the anterior chamber with no history of genetic disease,
      ocular trauma, or pseudoexfoliation that might predispose to a zonular
      abnormality. 

PMID- 25971182
TI  - Benign mixed tumor of the lacrimal sac.
AB  - Neoplasms of the lacrimal drainage system are uncommon, but potentially life
      threatening and are often difficult to diagnose. Among primary lacrimal sac
      tumors, benign mixed tumors are extremely rare. Histologically, benign mixed
      tumors have been classified as a type of benign epithelial tumor. Here we report
      a case of benign mixed tumor of the lacrimal sac. 

PMID- 25971183
TI  - Isolated abscess in superior rectus muscle in a child.
AB  - Pyomyositis is a primary bacterial infection of striated muscles nearly always
      caused by Staphylococcus aureus. Development of the intramuscular abscess
      involving the extra-ocular muscles (EOMs) remains an extremely rare process. We
      herein present a case of isolated EOM pyomyositis involving superior rectus
      muscle in a 2-year male child who was referred with complaints of swelling in
      left eye (LE) and inability to open LE since last 1-month. Orbital computed
      tomography (CT) scan showed a well-defined, hypo-dense, peripheral rim-enhancing
      lesion in relation to left superior rectus muscle suggestive of left superior
      rectus abscess. The abscess was drained through skin approach. We concluded that
      pyomyositis of EOM should be considered in any patient presenting with acute
      onset of orbital inflammation and characteristic CT or magnetic resonance imaging
      features. Management consists of incision and drainage coupled with antibiotic
      therapy. 

PMID- 25971184
TI  - Comparison of intracameral dexamethasone and intracameral triamcinolone acetonide
      injection at the end of phacoemulsification surgery.

PMID- 25971185
TI  - Respond to: Assessment of central corneal thickness and intraocular pressure in
      premature and full-term newborns.

PMID- 25971186
TI  - Evaluation of anterior chamber inflammation.

PMID- 25971187
TI  - Respond to: Safe endoresection.

PMID- 25971188
TI  - Role of part muscle vertical rectus transposition following periosteal fixation
      of the lateral rectus in exotropic Duane's retraction syndrome.

PMID- 25971189
TI  - Respond to: Management of exotropic Duane retraction syndrome.

PMID- 25971190
TI  - Comment on: Long-term results after primary intraocular lens implantation in
      children operated less than 2 years of age for congenital cataract.

PMID- 25971191
TI  - Conventional manual small-incision cataract surgery.

PMID- 25971192
TI  - Comment on: Intentional overcorrection in pediatric patients with intermittent
      exotropia: Indicated?

PMID- 25971193
TI  - Respond to: A study regarding efficacy of various intraocular lens power
      calculation formulas in a subset of Indian myopic population.

PMID- 25971194
TI  - Wearable red-green-blue quantum dot light-emitting diode array using high
      resolution intaglio transfer printing.
AB  - Deformable full-colour light-emitting diodes with ultrafine pixels are essential
      for wearable electronics, which requires the conformal integration on curvilinear
      surface as well as retina-like high-definition displays. However, there are
      remaining challenges in terms of polychromatic configuration, electroluminescence
      efficiency and/or multidirectional deformability. Here we present ultra-thin,
      wearable colloidal quantum dot light-emitting diode arrays utilizing the intaglio
      transfer printing technique, which allows the alignment of red-green-blue pixels
      with high resolutions up to 2,460 pixels per inch. This technique is readily
      scalable and adaptable for low-voltage-driven pixelated white quantum dot light
      emitting diodes and electronic tattoos, showing the best electroluminescence
      performance (14,000 cd m(-2) at 7 V) among the wearable light-emitting diodes
      reported up to date. The device performance is stable on flat, curved and
      convoluted surfaces under mechanical deformations such as bending, crumpling and
      wrinkling. These deformable device arrays highlight new possibilities for
      integrating high-definition full-colour displays in wearable electronics.

PMID- 25971195
TI  - An antialgal compound produced by Streptomyces jiujiangensis JXJ 0074(T).
AB  - Previous investigations suggested that Streptomyces jiujiangensis JXJ 0074(T) can
      secrete antialgal compounds. In this study, an antialgal compound was isolated
      from the cultured broth of S. jiujiangensis JXJ 0074(T) by using bioassay
      methods. Based on spectroscopic data, the active compound was identified as 2'
      deoxyadenosine, which exhibited a greater antialgal activity against
      cyanobacteria than its analogues such as adenosine, guanosine, and 2'
      deoxyguanosine. The antialgal activity of 2'-deoxyadenosine increased with the
      content and time. 2'-Deoxyadenosine severely damaged the vegetative cells of
      cyanobacteria, causing crumpling, collapse, expanding, perforation, breakage of
      filamentous cyanobacteria, and decrease of the chlorophyll. However, 2'
      deoxyadenosine seemed to have less impact on the morphology of heterocysts of
      filamentous cyanobacteria. The superoxide dismutase (SOD) activity in the treated
      cells of M. aeruginosa FACHB-905 initially increased with 31.14 +/- 2.00% higher
      than that of the control after 36 h and then decreased quickly. On the same time,
      there were rapid increases in superoxide anion radical (O2 (-)) and
      malondialdehyde (MDA) contents with 315.53 +/- 12.81 and 84.72 +/- 6.15% higher
      than these of the controls at 60 h, respectively. The intracellular microcystin
      LR (MC-LR) content in the treated cells of M. aeruginosa FACHB-905 increased by
      36.34 +/- 7.35% 1 day later, followed by a rapid decrease with a rate of 90.50 +/
      1.08% 8 days later, while the extracellular MC-LR content showed no significant
      difference with the control. Five days after adding 15 MUg/ml of 2'
      deoxyadenosine to the culture of M. aeruginosa FACHB-905, there was no 2'
      deoxyadenosine detected by HPLC, suggesting that 2'-deoxyadenosine completely
      degraded. This study provides a new clue to screen natural-based antialgal
      compounds from nucleoside analogues.

PMID- 25971196
TI  - Screening, identification, and characterization of a GH43 family beta
      xylosidase/alpha-arabinofuranosidase from a compost microbial metagenome.
AB  - A putative glycoside hydrolase family 43 beta-xylosidase/alpha
      arabinofuranosidase (CoXyl43) that promotes plant biomass saccharification was
      isolated via functional screening of a compost microbial metagenomic library and
      characterized. CoXyl43 promoted the saccharification of plant biomasses,
      including xylans (xylan and arabinoxylan), rice straw, and Erianthus, by
      degrading xylooligosaccharide residues to monosaccharide residues. The
      recombinant CoXyl43 protein exhibited both beta-xylosidase and alpha
      arabinofuranosidase activities for chromogenic substrates, with optimal activity
      at pH 7.5 and 55  degrees C. Both of these activities were inactivated by
      ethanol, dimethylsulfoxide, and zinc and copper ions but were activated by
      manganese ions. Only the beta-xylosidase activity of recombinant CoXyl43 was
      enhanced in the presence of calcium ions. These results indicate that CoXyl43
      exhibits unique enzymatic properties useful for biomass saccharification.

PMID- 25971197
TI  - Plant antifungal proteins and their applications in agriculture.
AB  - Fungi are far more complex organisms than viruses or bacteria and can develop
      numerous diseases in plants that cause loss of a substantial portion of the crop
      every year. Plants have developed various mechanisms to defend themselves against
      these fungi which include the production of low-molecular-weight secondary
      metabolites and proteins and peptides with antifungal activity. In this review,
      families of plant antifungal proteins (AFPs) including defensins, lectins, and
      several others will be summarized. Moreover, the application of AFPs in
      agriculture will also be analyzed. 

PMID- 25971198
TI  - Microbial diversity and their roles in the vinegar fermentation process.
AB  - Vinegar is one of the oldest acetic acid-diluted solution products in the world.
      It is produced from any fermentable sugary substrate by various fermentation
      methods. The final vinegar products possess unique functions, which are endowed
      with many kinds of compounds formed in the fermentation process. The quality of
      vinegar is determined by many factors, especially by the raw materials and
      microbial diversity involved in vinegar fermentation. Given that metabolic
      products from the fermenting strains are directly related to the quality of the
      final products of vinegar, the microbial diversity and features of the dominant
      strains involved in different fermentation stages should be analyzed to improve
      the strains and stabilize fermentation. Moreover, although numerous
      microbiological studies have been conducted to examine the process of vinegar
      fermentation, knowledge about microbial diversity and their roles involved in
      fermentation is still fragmentary and not systematic enough. Therefore, in this
      review, the dominant microorganism species involved in the stages of alcoholic
      fermentation and acetic acid fermentation of dissimilar vinegars were summarized.
      We also summarized various physicochemical properties and crucial compounds in
      disparate types of vinegar. Furthermore, the merits and drawbacks of vital
      fermentation methods were generalized. Finally, we described in detail the
      relationships among microbial diversity, raw materials, fermentation methods,
      physicochemical properties, compounds, functionality, and final quality of
      vinegar. The integration of this information can provide us a detailed map about
      the microbial diversity and function involved in vinegar fermentation. 

PMID- 25971199
TI  - Implications of endophyte-plant crosstalk in light of quorum responses for plant
      biotechnology.
AB  - Quorum sensing, the cell-to-cell communication system mediated by autoinducers,
      is responsible for regulation of virulence factors, infections, invasion,
      colonization, biofilm formation, and antibiotic resistance within bacterial
      populations. Concomitantly, quorum quenching is a process that involves
      attenuation of virulence factors by inhibiting or degrading quorum signaling
      autoinducers. Survival of endophytic microorganisms, commonly known as
      endophytes, in planta is a continuous melee with invading pathogens and pests. In
      order to survive in their microhabitats inside plants, endophytes have co-evolved
      to not only utilize an arsenal of biologically active defense compounds but also
      impede communication between invading pathogens. Such antivirulence strategies
      prevent pathogens from communicating with or recognizing each other and thus,
      colonizing plants. The quenching phenomena often involves microbial crosstalk
      within single or mixed population(s) vis-a-vis gene expression, and
      production/modulation of quenching enzymes coupled to various antagonistic and
      synergistic interactions. This concept is particularly interesting because it can
      be biotechnologically translated in the future to quorum inhibiting antivirulence
      therapies without triggering resistance in bacteria, which is currently a major
      problem worldwide that cannot be tackled only with antimicrobial therapies. In
      this mini-review, we highlight the quorum quenching capacity of endophytes with
      respect to attenuation of virulence factors and aiding in plant defense response.
      Further, benefits and potential challenges of using such systems in biotechnology
      are discussed. 

PMID- 25971200
TI  - A novel approach for in vitro meat production.
AB  - The present review describes the possibility of in vitro meat production with the
      help of advanced co-culturing methods. In vitro meat production method could be a
      possible alternative for the conventional meat production. Originally, the
      research on in vitro meat production was initiated by the National Aeronautics
      and Space Administration (NASA) for space voyages. The required key qualities for
      accepting in vitro meat for consumption would be good efficiency ratio, increased
      protein synthesis rate in skeletal muscles, and mimicking the conventional meat
      qualities. In vitro culturing of meat is possible with the use of skeletal muscle
      tissue engineering, stem cell, cell co-culture, and tissue culture methods. Co
      culture of myoblast and fibroblast is believed as one of the major techniques for
      in vitro meat production. In our lab, we have co-cultured myoblast and
      fibroblast. We believe that a billion pounds of in vitro meat could be produced
      from one animal for consumption. However, we require a great deal of research on
      in vitro meat production. 

PMID- 25971201
TI  - Erratum to: Removal mechanism of low-concentration Cr (VI) in a submerged
      membrane bioreactor activated sludge system.

PMID- 25971202
TI  - Men's Responses to Online Smoking Cessation Resources for New Fathers: The
      Influence of Masculinities.
AB  - BACKGROUND: Smoking cessation is the single most important step to preventing
      cancer. Drawing on previous research, Web-based resources were developed to
      complement a program to support expectant and new fathers to quit smoking.
      OBJECTIVE: The objectives of this research were to: (1) describe the responses of
      expectant and new fathers who smoke or had recently quit smoking to the website
      resources, and (2) explore how masculinities shape men's responses to and
      experiences with online smoking cessation resources. METHODS: Using semi
      structured, individual face-to-face interviews, the Dads in Gear Web-based
      resources were reviewed and evaluated by 20 new fathers who smoked or had
      recently quit smoking. The data were transcribed and analyzed using NVivo 8
      qualitative data analysis software. RESULTS: We describe the fathers' reactions
      to various components of the website, making connections between masculinities
      and fathering within 5 themes: (1) Fathering counts: gender-specific parenting
      resources; (2) Measuring up: bolstering masculine identities as fathers; (3)
      Money matters: triggering masculine virtues related to family finances; (4)
      Masculine ideals: father role models as cessation aids; and (5) Manly moves:
      physical activity for the male body. CONCLUSIONS: A focus on fathering was an
      effective draw for men to the smoking cessation resources. The findings provide
      direction for considering how best to do virtual cessation programs as well as
      other types of online cancer prevention programs for men.

PMID- 25971203
TI  - Do lower urinary tract symptoms predict cardiovascular diseases in older men? A
      systematic review and meta-analysis.
AB  - PURPOSE: To study the incidence of CVD in men at risk, with and without LUTS.
      METHODS: We searched all longitudinal studies describing the association between
      LUTS and CVD (mortality) in October 2013 and December 2014 using MEDLINE, EMBASE,
      and the Cochrane Library Central Register. PRISMA criteria were met. RESULTS: We
      included five studies with 6027 men with LUTS and 18,993 men without LUTS in the
      meta-analyses, with a follow-up period varying from 5 to 17 years. Studies
      totalled 2780 CVD events. No clear association between CVD and LUTS was
      demonstrated [pooled effect size: hazard ratio 1.09 (95 % CI 0.90-1.31); p =
      0.40]. Two other studies reported the association between nocturia and (CVD)
      mortality. CVD-specific mortality risk was approximately two times higher for
      Japanese men with nocturia (357 men aged 70 years and over, 5-year follow-up). A
      univariable association between nocturia and all-cause mortality was found in
      Dutch men, but not in age-adjusted analyses (1114 men aged 50-78 years, 13-year
      follow-up). CONCLUSION: This meta-analysis conducted on longitudinal studies does
      not confirm LUTS to be a predictor of CVD in men without a history of CVD,
      despite the observed association between LUTS and CVD in cross-sectional studies.

PMID- 25971204
TI  - Differences in renal stone treatment and outcomes for patients treated either
      with or without the support of a ureteral access sheath: The Clinical Research
      Office of the Endourological Society Ureteroscopy Global Study.
AB  - PURPOSE: To describe the differences in the treatment and the outcomes of renal
      stones treated with flexible ureteroscopy (URS) either with or without the
      support of a ureteral access sheath (UAS). METHODS: The Clinical Research Office
      of the Endourological Society URS Global Study involved the collection of
      prospective data from consecutive patients treated with URS at centers around the
      world over a 1-year period. Baseline characteristics, stone location, treatment
      details, postoperative outcomes and complications were recorded. Inverse
      probability-weighted regression adjustment (IPWRA) analyses were conducted on
      outcome from patients treated with or without the use of a UAS to determine the
      impact on stone-free rates (SFRs). RESULTS: Of 2239 patients treated with
      flexible URS, 1494 (67 %) patients were treated with the use of a UAS and 745 (33
      %) without a UAS. The IPWRA analyses conducted on 1827 patients with complete
      data and based on treatment and outcome models showed that if URS procedures were
      performed without the use of an UAS, the average stone-free rate would be 0.504
      compared with 0.753 with a UAS. This average treatment effect of 0.248 was not
      significant (P = 0.604). Using IPWRA analysis on only the treated population in
      the estimations revealed no significant difference between using and not using a
      UAS (31 %; ATET: 0.311; P = 0.523). CONCLUSIONS: The study showed no difference
      in SFR when a UAS was used or not. Whereas UAS did not increase the risk of
      ureteral damage or bleeding, postoperative infectious complications were reduced.

PMID- 25971205
TI  - Ultra-mini PCNL versus flexible ureteroscopy: a matched analysis of analgesic
      consumption and treatment-related patient satisfaction in patients with renal
      stones 10-35 mm.
AB  - PURPOSE: To compare ultra-mini PCNL (UMP) and flexible ureteroscopy (fURS) for
      the treatment of medium- to large-sized renal stones with a focus on patients'
      postsurgical cumulative analgesic consumption and treatment-related satisfaction.
      METHODS: Twenty-five patients treated by UMP between April 2013 and October 2014
      were matched to data of 25 fURS patients from an existing database. Clinical
      outcome parameters were recorded prospectively. Postoperative analgesic
      consumption was assessed using the Cumulative Analgesic Consumption Score (CACS),
      and satisfaction was measured with the Freiburg Index of Patient Satisfaction
      (FIPS) questionnaire. RESULTS: Perioperative outcome parameters showed no
      significant differences except for mean operating times (fURS 98.52 min, UMP
      130.12 min [p = 0.002]) and hospital stay (fURS 67.2 h, UMP 91.5 h [p = 0.04]).
      Primary stone-free rate was 96 % in fURS and 92 % in UMP. Complications Clavien
      grade 2 or 3 occurred in 16 % of UMP patients and in 4 % of fURS patients.
      Postsurgical cumulative analgesic consumption was almost identical in both groups
      with CACSs of 6.96 (0-15) for fURS and 6.8 (0-23) for UMP. Patients' satisfaction
      was high in both techniques: FIPS score in fURS 1.67 (1-3) and 1.73 (1-4) in UMP
      (scale 1-6). CONCLUSIONS: Treatment of medium- to large-sized renal stones is
      safe and highly effective by both UMP and fURS. Moreover, both treatments yield
      comparable postsurgical analgesic requirements and high patient satisfaction
      scores. Patient-related factors (anatomical and stone related) and availability
      of technical equipment and surgical expertise appear to be the most important
      determining factors in treatment planning.

PMID- 25971210
TI  - Overexpression of microRNA-95-3p suppresses brain metastasis of lung
      adenocarcinoma through downregulation of cyclin D1.
AB  - Despite great efforts to improve survival rates, the prognosis of lung cancer
      patients is still very poor, mainly due to high invasiveness. We developed brain
      metastatic PC14PE6/LvBr4 cells through intracardiac injection of lung
      adenocarcinoma PC14PE6 cells. Western blot and RT-qPCR analyses revealed that
      PC14PE6/LvBr4 cells had mesenchymal characteristics and higher invasiveness than
      PC14PE6 cells. We found that cyclin D1 was upregulated, miR-95-3p was inversely
      downregulated, and pri-miR-95 and its host gene, ABLIM2, were consistently
      decreased in PC14PE6/LvBr4 cells. MiR-95-3p suppressed cyclin D1 expression
      through direct binding to the 3' UTR of cyclin D1 mRNA and suppressed
      invasiveness, proliferation, and clonogenicity of PC14PE6/LvBr4 cells. Ectopic
      cyclin D1 reversed miR-95-3p-mediated inhibition of invasiveness and
      clonogenicity, demonstrating cyclin D1 downregulation is involved in function of
      miR-95-3p. Using bioluminescence imaging, we found that miR-95-3p suppressed
      orthotopic tumorigenicity and brain metastasis in vivo and increased overall
      survival and brain metastasis-free survival. Consistent with in vitro metastatic
      cells, the levels of miR-95-3p, pri-miR-95, and ABLIM2 mRNA were decreased in
      brain metastatic tissues compared with lung cancer tissues and higher cyclin D1
      expression was involved in poor prognosis. Taken together, our results
      demonstrate that miR-95-3p is a potential therapeutic target for brain metastasis
      of lung adenocarcinoma cells.

PMID- 25971209
TI  - MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human
      pancreatic cancer cells sensitivity to gemcitabine.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with
      less than 5% of patients surviving 5 years beyond diagnosis. Systemic therapies,
      particularly gemcitabine, have a modest clinical benefit, but chemoresistance
      limits their efficacy. Here, we demonstrate that plasma miR-33a levels positively
      correlated with miR-33a levels in tumor tissues of patients with PDAC and are a
      good prognostic indicator of overall survival. Overexpression of miR-33a
      inhibited tumor cell proliferation and increased the chemosensitivity to
      gemcitabine both in vitro and in vivo. Moreover, miR-33a targets Pim-3 directly
      in PDAC. Pim-3 expression was a prognostic indicator related to poor survival in
      pancreatic cancer patients. Plasma miR-33a levels were significantly lower in
      pancreatic cancer patients with high Pim-3 protein expression than in healthy
      controls. Furthermore, overexpression of miR-33a in pancreatic cancer cell lines
      suppressed Pim-3 expression, leading to downregulation of the AKT/Gsk-3beta/beta
      catenin pathway. Overall, these results indicate that miR-33a functions as a
      tumor suppressor that downregulates Pim-3 kinase expression to inhibit both
      pancreatic tumor growth and gemcitabine resistance via the AKT/beta-catenin
      pathway. Hence, detection of plasma miR-33a may be a simple and convenient method
      of predicting therapeutic responses. 

PMID- 25971211
TI  - Type II transglutaminase stimulates epidermal cancer stem cell epithelial
      mesenchymal transition.
AB  - Type II transglutaminase (TG2) is a multifunctional protein that has recently
      been implicated as having a role in ECS cell survival. In the present study we
      investigate the role of TG2 in regulating epithelial mesenchymal transition (EMT)
      in ECS cells. Our studies show that TG2 knockdown or treatment with TG2
      inhibitor, results in a reduced EMT marker expression, and reduced cell migration
      and invasion. TG2 has several activities, but the most prominent are its
      transamidase and GTP binding activity. Analysis of a series of TG2 mutants
      reveals that TG2 GTP binding activity, but not the transamidase activity, is
      required for expression of EMT markers (Twist, Snail, Slug, vimentin,
      fibronectin, N-cadherin and HIF-1alpha), and increased ECS cell invasion and
      migration. This coupled with reduced expression of E-cadherin. Additional studies
      indicate that NFI degrees B signaling, which has been implicated as mediating TG2
      impact on EMT in breast cancer cells, is not involved in TG2 regulation of EMT in
      skin cancer. These studies suggest that TG2 is required for maintenance of ECS
      cell EMT, invasion and migration, and suggests that inhibiting TG2 GTP binding/G
      protein related activity may reduce skin cancer tumor survival.

PMID- 25971212
TI  - Peripapillary choroidal thickness in patients with early age-related macular
      degeneration and reticular pseudodrusen.
AB  - PURPOSE: The purpose of this study was to investigate peripapillary and macular
      choroidal thickness (CT) in patients with early age-related macular degeneration
      (AMD) with or without reticular pseudodrusen (RPD). METHODS: We investigated the
      medical records of 89 patients (89 eyes) with early AMD. The eyes were grouped
      into three categories according to the extent of RPD: no RPD, localized RPD, and
      diffuse RPD. Peripapillary and macular CT were measured with images obtained by
      spectral domain optical coherence tomography. CT in the peripapillary and macular
      areas was compared among groups. RESULTS: Both RPD groups exhibited an older
      subject age and a greater female predominance compared to the non-RPD group (P =
      0.007 and P = 0.030, respectively). Macular and peripapillary CT were different
      among the three groups (all, P < 0.001), and both RPD groups showed a thinner
      choroid in all areas compared to the non-RPD group after adjusting for age and
      sex (all, P <= 0.016). Temporal peripapillary and nasal macular CT at 500 MUm and
      1500 MUm, respectively, from the fovea in eyes with diffuse RPD were
      significantly thinner than that in eyes with localized RPD (P = 0.008, P = 0.016
      and P < 0.001, respectively). CONCLUSIONS: In addition to the macular area, the
      peripapillary CT, including the area outside the macula, was thinner in eyes with
      RPD than in those without RPD. Significant differences in the papillomacular
      choroid were observed based on RPD distribution type, which suggests that
      variation in CT is based on the extent of RPD.

PMID- 25971214
TI  - Pharmacist collaborative practice agreement for the management of anemia in
      malignant disease with erythropoiesis-stimulating agents.
AB  - PURPOSE: Erythropoiesis-stimulating agents (ESAs) reduce transfusions and
      increase hemoglobin levels in patients with anemia of malignant disease. A
      medication guideline and pharmacist collaborative practice agreement (CPA) were
      developed and implemented to standardize ESA prescribing workflow. The use of
      ESAs in malignant diseases, in accordance with institutional guidelines, was
      evaluated to ensure safe and effacious use. METHODS: An observational study was
      conducted on all ESA doses given throughout a health system's cancer clinics
      prior to and after implementation of an ESA guideline and pharmacist CPA. The
      primary outcome measured was ESA therapy initiated in accordance with guidelines
      before and after the intervention. Secondary outcomes evaluated were nurse and
      pharmacist satisfaction, vitals recorded prior to dose, and transfusion rates in
      patients receiving ESA therapy before and after the intervention. RESULTS: In the
      pre-implementation group, criteria for initiation were not met by any of the 39
      patients; prior to therapy, 5.1 % of patients had not had hemoglobin drawn, 23 %
      of patients had no iron studies completed, and 29.4 % of myelodysplastic syndrome
      (MDS) patients had no erythropoietin levels drawn. In the post-implementation
      group, prior to therapy, all patients had hemoglobin levels drawn, 16.67 % did
      not have iron studies completed, and all MDS patients had erythropoietin levels
      drawn appropriately. Chemotherapy-induced anemia (CIA) patients in the pre
      implementation group had 71.4 % compliance with receiving chemotherapy within 8
      weeks of ESA dose, and the post-implementation group had 100 % compliance.
      CONCLUSION: An ESA guideline and pharmacist CPA aligned prescribing practices
      with the NCCN and ASCO guidelines and improved staff satisfaction.

PMID- 25971213
TI  - The role of physical rehabilitation in stem cell transplantation patients.
AB  - The purpose of this paper is to review the evidence for the role of physical
      rehabilitation in stem cell transplantation patients. We will also review the
      literature and discuss professional experiences on how rehabilitation can play a
      role in stem cell transplant care and survivorship. Hematopoietic stem cell
      transplantation (HCT) is a procedure that has evolved substantially over the
      years to help treat multiple conditions, particularly hematologic malignancies.
      HCT can be very stressful on the body and can leave patients weakened and
      sometimes quite debilitated. Supportive care measures have advanced to improve
      the quality of life and overall survival of HCT survivors. One key component of
      improved supportive care is gaining increased attention, and that is physical
      medicine and rehabilitation. Its role in HCT survivorship care is expanding, and
      new insight and research within the discipline have focused on fatigue,
      inflammation, exercise, and the development of structured rehabilitation programs
      to improve the musculoskeletal sequelae of transplantation. This literature
      review has demonstrated the utility of physical rehabilitation in HCT, its impact
      on cancer-related fatigue, and to outline the current state of the literature on
      these topics. The paper delves into a background of HCT. Cancer-related fatigue
      in HCT is then discussed and summarized, and the role that exercise plays in
      modifying such fatigue is outlined. We then outline the models and the impact
      that physical rehabilitation may play in HCT recipients.

PMID- 25971215
TI  - Mexican-Origin Youth Participation in Extracurricular Activities: Predicting
      Trajectories of Involvement from 7th to 12th Grade.
AB  - The potential benefits of participation in extracurricular activities may be
      especially important for youth who are at risk for academic underachievement,
      such as low income Mexican-origin youth in the U.S. To advance understanding of
      factors that drive participation for this population, this study examined Mexican
      origin youth's trajectories of participation in extracurricular activities across
      Grades 7-12 and tested theoretically-derived predictors of these trajectories.
      Participants were 178 adolescents (53.9 % Female, Mage = 12.28) and their mothers
      who separately completed in-home interviews. Youth reported the frequency of
      their participation across a range of extracurricular activities. Latent growth
      curve models of overall extracurricular activities participation, sports
      participation, and fine arts participation were individually estimated via
      structural equation modeling. The findings demonstrated developmental declines in
      overall participation and in sports participation. For fine arts, declines in
      participation in middle school were followed by subsequent increases during high
      school (a curvilinear pattern). Motivationally-salient predictors of
      participation trajectories included youth's traditional cultural values
      orientation (sports), the mothers' educational aspirations for the youth (sports,
      fine arts, overall activity), and youth gender (sports, fine arts). Overall, the
      results suggest variability in participation trajectories based on program type,
      and highlight the need for additional research to enhance our understanding of
      the impact of culturally-relevant predictors on participation over time. 

PMID- 25971216
TI  - Understanding the Link Between Pubertal Timing in Girls and the Development of
      Depressive Symptoms: The Role of Sexual Harassment.
AB  - The link between sexual maturation, or pubertal timing, in girls and adolescent
      depressive symptoms is well-documented, but the underlying processes remain
      unclear. We examined whether sexual harassment, which has previously been linked
      to both pubertal timing and depressive symptoms, mediates this link, using a two
      wave longitudinal study including 454 girls in 7th (M age  = 13.42, SD = .53) and
      8th grade (M age  = 14.42, SD = .55). Pubertal timing was linked to depressive
      symptoms in both age groups, and predicted an increase in depressive symptoms
      among the 7th graders. Sexual harassment significantly mediated the link between
      pubertal timing and depressive symptoms among the 7th, but not the 8th grade
      girls. Together, our findings suggest that one way to prevent depressive symptoms
      among early-maturing girls could be to address sexual harassment in preventive
      intervention in early adolescence. 

PMID- 25971217
TI  - Towards universal civil registration and vital statistics systems: the time is
      now.
AB  - The health and development challenges of the coming decades cannot be tackled
      effectively without reliable data for births, deaths, and causes of death, which
      only a comprehensive civil registration and vital statistics (CRVS) system can
      deliver. Alternative methods such as surveys, censuses, or surveillance are not
      adequate substitutes from a statistical perspective, and do not provide
      individuals with the legal documentation they need to benefit from services and
      participate fully in a modern society. Research is needed to generate and
      disseminate evidence about which CRVS strategies work best in which contexts and
      to ensure that the potential benefits of innovation are successfully scaled up,
      and that possible pitfalls are avoided. Research findings need to be compiled and
      made readily accessible to users for policy making, programming, and practice.
      Modernisation of CRVS systems necessitates new, broad-based national and
      international coalitions. The global architecture for CRVS, so far dominated by
      UN agencies, should extend to include bilateral donors, funds, foundations, non
      governmental organisations, the private sector, academic institutions, and civil
      society. This change is essential to ensure that further development of CRVS
      systems is inclusive, participatory, multisectoral, and has a strong evidence
      base. 

PMID- 25971218
TI  - A global assessment of civil registration and vital statistics systems:
      monitoring data quality and progress.
AB  - Increasing demand for better quality data and more investment to strengthen civil
      registration and vital statistics (CRVS) systems will require increased emphasis
      on objective, comparable, cost-effective monitoring and assessment methods to
      measure progress. We apply a composite index (the vital statistics performance
      index [VSPI]) to assess the performance of CRVS systems in 148 countries or
      territories during 1980-2012 and classify them into five distinct performance
      categories, ranging from rudimentary (with scores close to zero) to satisfactory
      (with scores close to one), with a mean VSPI score since 2005 of 0.61 (SD 0.31).
      As expected, the best performing systems were mostly in the European region, the
      Americas, and Australasia, with only two countries from east Asia and Latin
      America. Most low-scoring countries were in the African or Asian regions.
      Globally, only modest progress has been made since 2000, with the percentage of
      deaths registered increasing from 36% to 38%, and the percentage of children aged
      under 5 years whose birth has been registered increasing from 58% to 65%.
      However, several individual countries have made substantial improvements to their
      CRVS systems in the past 30 years by capturing more deaths and improving accuracy
      of cause-of-death information. Future monitoring of the effects of CRVS
      strengthening will greatly benefit from application of a metric like the VSPI,
      which is objective, costless to compute, and able to identify components of the
      system that make the largest contributions to good or poor performance. 

PMID- 25971219
TI  - Everyone counts--so count everyone.

PMID- 25971220
TI  - AVERT: a major milestone in stroke research.

PMID- 25971221
TI  - Civil registration as a means to promote human security.

PMID- 25971222
TI  - Are well functioning civil registration and vital statistics systems associated
      with better health outcomes?
AB  - In this Series paper, we examine whether well functioning civil registration and
      vital statistics (CRVS) systems are associated with improved population health
      outcomes. We present a conceptual model connecting CRVS to wellbeing, and
      describe an ecological association between CRVS and health outcomes. The
      conceptual model posits that the legal identity that civil registration provides
      to individuals is key to access entitlements and services. Vital statistics
      produced by CRVS systems provide essential information for public health policy
      and prevention. These outcomes benefit individuals and societies, including
      improved health. We use marginal linear models and lag-lead analysis to measure
      ecological associations between a composite metric of CRVS performance and three
      health outcomes. Results are consistent with the conceptual model: improved CRVS
      performance coincides with improved health outcomes worldwide in a temporally
      consistent manner. Investment to strengthen CRVS systems is not only an important
      goal for individuals and societies, but also a development imperative that is
      good for health. 

PMID- 25971223
TI  - Alan Lopez: making everyone count.

PMID- 25971224
TI  - Civil registration and vital statistics: progress in the data revolution for
      counting and accountability.
AB  - New momentum for civil registration and vital statistics (CRVS) is building,
      driven by the confluence of growing demands for accountability and results in
      health, improved equity, and rights-based approaches to development challenges,
      and by the immense potential of innovation and new technologies to accelerate
      CRVS improvement. Examples of country successes in strengthening of hitherto weak
      systems are emerging. The key to success has been to build collaborative
      partnerships involving local ownership by several sectors that span registration,
      justice, health, statistics, and civil society. Regional partners can be
      important to raise awareness, set regional goals and targets, foster country-to
      country exchange and mutual learning, and build high-level political commitment.
      These regional partners continue to provide a platform through which country
      stakeholders, development partners, and technical experts can share experiences,
      develop and document good practices, and propose innovative approaches to tackle
      CRVS challenges. This country and regional momentum would benefit from global
      leadership, commitment, and support. 

PMID- 25971225
TI  - The usefulness of a perfusion balloon in a case of late stent thrombosis that
      caused simultaneous double vessel occlusion.
AB  - Simultaneous stent thrombosis in different coronary arteries requires rapid
      management. A 70-year-old man experienced simultaneous stent thrombosis at the
      left anterior descending and circumflex arteries. We used a perfusion balloon to
      prevent thrombus production at the left anterior descending artery, and completed
      percutaneous coronary intervention at the left circumflex artery in 10 min. The
      perfusion balloon was dilated during the procedure. In both vessels, Thrombolysis
      in myocardial infarction flow grade 3 was achieved after balloon deflation. Thus,
      use of a perfusion balloon for simultaneous double vessel occlusion helped avoid
      the need for redundant stent placement and shortened the procedure time. 

PMID- 25971226
TI  - Unique Group 1 cations stabilised by homoleptic neutral phosphine coordination.
AB  - Homoleptic coordination of the neutral diphosphines Me2P(CH2)2PMe2 and o
      C6H4(PMe2)2 to the hard Li(+) and Na(+) cations is achieved using
      Li[Al{OC(CF3)3}4] and Na[B{3,5-(CF3)2-C6H3}4] as 'naked' cation sources.
      Crystallographic, solid state and solution multinuclear NMR studies confirm
      distorted octahedral coordination solely via three chelating diphosphines in
      these unique species. 

PMID- 25971227
TI  - The analysis of dyadic deaths.
AB  - In the work we analyze three cases of unusual dyadic deaths when the perpetrator
      of homicide committed suicide shortly after the murder. In the first case a man
      stabbed his girlfriend with a knife and subsequently committed a car crash
      suicide. In the second case an apparent simultaneous hanging of a married couple
      turned out to be homicide-suicide act. In the last case a man shot his ex-wife
      while she was on a walk with their dog and in a short time turned the gun against
      himself. 

PMID- 25971228
TI  - [Two sudden deaths of children with mesenterium commune -- a case report].
AB  - Congenital anomalies of the digestive system represent a complicated topic
      concerning many medical specializations. The goal of this article is to describe
      two cases of children with mesenterium commune. First was an infant (5.5 months
      old female) who died shortly after being admitted to hospital with acute
      bronchitis, vomiting and diarrhoea. The autopsy revealed the cause of death-
      volvulus of the entire small intestine and the first portion of the large
      intestine with haemorrhagic infarsation of the intestinal wall in an infant with
      congenital anomaly of intestinal fixation--mesenterium commune. Second case was a
      2.5 years old female after two heart surgeries, with pulmonary hypertension, who
      died suddenly at home. The cause of death was volvulus of a portion of the small
      intestine with haemorrhagic infarsation of the intestinal wall and also
      mesenterium commune. Congenital malpositions of the intestine originate due to
      malrotation and malfixation of the intestine during prenatal and early postnatal
      period. This wide range of the individuals developmental disorders always result
      in a condition where the topographical findings in the abdominal cavity are not
      as commonly found. Abnormally positioned intestines cannot develop a normal
      mesentery and are prone to volvulus, which represents the most serious
      complication with acute abdominal symptoms and when diagnosed late, it can lead
      to sudden death. Whilst performing autopsies such cases are rarely seen. However
      in forensic medicine and also in clinical practice it is important to consider
      intestinal malposition as a cause of acute abdomen.

PMID- 25971229
TI  - [Confrontation of knowledge on alcohol concentration in blood and in exhaled
      air].
AB  - The authors of the paper give a brief historical overview of the development of
      experimental alcohology in the former Czechoslovakia. Enhanced attention is paid
      to tests of work quality control of toxicological laboratories. Information on
      results of control tests of blood samples using the method of gas chromatography
      in Slovakia and within a world-wide study "Eurotox 1990" is presented. There are
      pointed out the pitfalls related to objective evaluation of the analysis results
      interpreting alcohol concentration in biological materials and the associated
      need to eliminate a negative influence of the human factor. The authors recommend
      performing analyses of alcohol in biological materials only at accredited
      workplaces and in the case of samples storage to secure a mandatory inhibition of
      phosphorylation process. There are analysed the reasons of numerical differences
      of analyses while taking evidence of alcohol in blood and in exhaled air. The
      authors confirm analysis accuracy using the method of gas chromatography along
      with breath analysers of exhaled air. They highlight the need for making the
      analysis results more objective also through confrontation with the results of
      clinical examination and with examined circumstances. The authors suggest a
      method of elimination of the human factor, the most frequently responsible for
      inaccuracy, to a tolerable level (safety factor) and the need of sample analysis
      by two methods independent of each other or the need of analysis of two
      biological materials. 

PMID- 25971230
TI  - A fatal case of poisoning with ethanol and psychotropic drugs with putrefactive
      changes.
AB  - We present a fatal case involving poisoning with paroxetine, flunitrazepam, and
      ethanol, with putrefactive changes. Quantitative toxicological analysis showed
      that the concentrations of paroxetine and 7-aminoflunitrazepam, a metabolite of
      flunitrazepam, in the femoral blood were 0.28 ug/ml and 0.17 ug/ml, respectively.
      We also detected an ethanol level of 2.90 mg/ml and an n-propanol level of 0.10
      mg/ml. We concluded that the cause of death was due to the interaction of
      paroxetine, flunitrazepam, and ethanol. The effects of putrefactive changes
      should be considered during forensic toxicological evaluation. 

PMID- 25971231
TI  - Treatment of cerebral cavernous malformations: where do we stand?

PMID- 25971232
TI  - Solution NMR assignment of the cryptic sixth TOG domain of mini spindles.
AB  - TOG domains contribute to the organisation of microtubules through their ability
      to bind tubulin. They are found in members of the XMAP215 family of proteins,
      which act as microtubule polymerases and fulfill important roles in the formation
      of the mitotic spindle and in the assembly of kinetochore fibres. We recently
      identified a cryptic TOG domain in the XMAP215 family proteins, chTOG and its
      Drosophila homologue, mini spindles. This domain is not part of the well
      established array of TOG domains involved in tubulin polymerisation. Instead it
      forms part of a binding site for TACC3 family proteins. This interaction is
      required for the assembly of kinetochore bridges in a trimeric complex with
      clathrin. Here we present the first NMR assignment of a sixth TOG domain from
      mini spindles as a first step to elucidate its structure and function. 

PMID- 25971233
TI  - Pressure-controlled injection of guar gum stabilized microscale zerovalent iron
      for groundwater remediation.
AB  - The paper reports a pilot injection test of microsized zerovalent iron (mZVI)
      dispersed in a guar gum shear thinning solution. The test was performed in the
      framework of the EU research project AQUAREHAB in a site in Belgium contaminated
      by chlorinated aliphatic hydrocarbons (CAHs). The field application was aimed to
      overcome those critical aspects which hinder mZVI field injection, mainly due to
      the colloidal instability of ZVI-based suspensions. The iron slurry properties
      (iron particles size and concentration, polymeric stabilizer type and
      concentration, slurry viscosity) were designed in the laboratory based on several
      tests (reactivity tests towards contaminants, sedimentation tests and rheological
      measurements). The particles were delivered into the aquifer through an injection
      well specifically designed for controlled-pressure delivery (approximately 10
      bars). The well characteristics and the critical pressure of the aquifer (i.e.
      the injection pressure above which fracturing occurs) were assessed via two
      innovative injection step rate tests, one performed with water and the other one
      with guar gum. Based on laboratory and field preliminary tests, a flow regime at
      the threshold between permeation and preferential flow was selected for mZVI
      delivery, as a compromise between the desired homogeneous distribution of the
      mZVI around the injection point (ensured by permeation flow) and the fast and
      effective injection of the slurry (guaranteed by high discharge rates and
      injection pressure, resulting in the generation of preferential flow paths). A
      monitoring setup was designed and installed for the real-time monitoring of
      relevant parameters during injection, and for a fast determination of the spatial
      mZVI distribution after injection via non-invasive magnetic susceptibility
      measurements. 

PMID- 25971234
TI  - The effects of the herbicide atrazine on freshwater snails.
AB  - Atrazine has been shown to affect freshwater snails from the subcellular to
      community level. However, most studies have used different snail species,
      methods, endpoints, and atrazine exposure concentrations, resulting in some
      conflicting results and limiting our understanding. The goal of this study was to
      address these concerns by (1) investigating the acute and chronic effects of
      atrazine on four species of freshwater snails (Biomphalaria glabrata, Helisoma
      trivolvis, Physa acuta, and Stagnicola elodes) using the same methods, endpoints,
      and concentrations, and (2) summarizing the current literature pertaining to the
      effects of atrazine on freshwater snails. We conducted a 48 h acute toxicity test
      with an atrazine concentration higher than what typically occurs in aquatic
      environments (1000 ug/L). Additionally, we exposed snails to environmentally
      relevant atrazine concentrations (0, 0.3, 3, and 30 ug/L) for 28 days and
      assessed snail survival, growth, and reproduction. We also summarized all known
      literature pertaining to atrazine effects on freshwater snails. The literature
      summary suggests snails are often affected by environmentally relevant atrazine
      concentrations at the subcellular and cellular levels. These effects are
      typically not transitive to effects on survival, growth, or reproduction at the
      same concentrations. Our acute exposures corroborate the general trend of no
      direct effect on snail populations as atrazine did not directly affect the
      survival of any of the four snail species. Similarly, environmentally relevant
      concentrations did not significantly affect the survival, growth, or reproduction
      of any snail species. These results indicate that, in the absence of other
      possible stressors, the direct effects of environmentally relevant atrazine
      concentrations may not be realized at the snail population level.

PMID- 25971235
TI  - Esophageal stenting in caustic injuries: a modified technique to avoid
      laparotomy.
AB  - OBJECTIVE: To compare the outcomes of a modified laparoscopic intraluminal
      stenting with the conventional laparatomic technique in patients with esophageal
      caustic injuries. METHODS: A total of 103 patients with esophageal burns were
      included in this retrospective analysis. Patients were candidates for esophageal
      stenting to prevent future stenosis. According to patient preference, stenting
      was done with either the innovatory stent with the modified technique (52
      patients) or the conventional method that required laparotomy (51 patients). The
      modified technique consists of placing an inflation balloon stent via
      laparoscopy. Overall mortality and complications after follow-up period (3
      months) were compared between the two groups. RESULTS: Two perioperative
      mortalities were seen, one in each group. Except one patient in the modified
      technique, all patients returned to normal intake after 3 months of follow-up.
      However, five patients of the modified group and three in the conventional group
      developed esophageal strictures (p > 0.05). Gastric outlet obstruction was
      observed in three patients of the modified group and one in the conventional
      group (p > 0.05). DeMeester scores showed that there was no gastro-esophageal
      reflux in both groups (p > 0.05). CONCLUSION: Our results show that the modified
      technique can reach the efficacy of the conventional method without requiring
      laparotomy. Thus, far several studies have demonstrated the advantages of
      laparoscopy over laparotomy. Thus, and in line with the clinical guidelines of
      the Society of American Gastrointestinal and Endoscopic Surgeons, we recommend
      using the presented modified technique in patients with caustic esophageal
      injuries.

PMID- 25971236
TI  - Early and late outcomes of AVR with aortic annular enlargement in octogenarian.
AB  - OBJECTIVE: There is no clear consensus on the procedures for octogenarians with a
      small aortic annulus who require aortic valve replacement (AVR). We evaluated
      surgical results in octogenarians who underwent AVR with aortic annular
      enlargement, Nicks procedure, for aortic stenosis with a small aortic annulus.
      METHODS: Between January 2001 and March 2014, 131 octogenarian patients were
      treated at our institution. Nineteen patients received AVR with aortic annular
      enlargement (AAE group), and the others received standard AVR without annular
      enlargement (sAVR group). We compared early and late outcomes between the two
      groups. RESULTS: There were no significant differences in early complications
      between the groups. The rates for use of a mechanical valve (32 vs 22 %, p =
      0.590), in-hospital mortality (5.3 vs 5.4 %, p = 1.000), and severe patient
      prosthesis mismatch (PPM) (0 vs 6.3 %, p = 0.593) were also similar between the
      AAE and sAVR group. In the AAE group, there was no cardiac-related death,
      bleeding event, thromboembolism, or stroke during the follow-up period (mean 37.6
      months). The rates of freedom from cardiac events at 8 years were 94 % in the AAE
      group and 57 % in the sAVR group (p = 0.292). The overall survival rates at 8
      years were 77 % in the AAE group and 77 % in sAVR group (p = 0.462). There were
      no significant differences in these rates between the groups. CONCLUSION: AVR
      with aortic annular enlargement in octogenarians with small aortic annulus was
      safe and led to good operative and long-term outcomes.

PMID- 25971237
TI  - Why history matters for quantitative target setting: Long-term trends in
      socioeconomic and racial/ethnic inequities in US infant death rates (1960-2010).
AB  - Policy-oriented population health targets, such as the Millennium Development
      Goals and national targets to address health inequities, are typically based on
      trends of a decade or less. To test whether expanded timeframes might be more
      apt, we analyzed 50-year trends in US infant death rates (1960-2010) jointly by
      income and race/ethnicity. The largest annual per cent changes in the infant
      death rate (between -4 and -10 per cent), for all racial/ethnic groups, in the
      lowest income quintile occurred between the mid-1960s and early 1980s, and in the
      second lowest income quintile between the mid-1960s and 1973. Since the 1990s,
      these numbers have hovered, in all groups, between -1 and -3 per cent. Hence, to
      look back only 15 years (in 2014, to 1999) would ignore gains achieved prior to
      the onset of neoliberal policies after 1980. Target setting should be informed by
      a deeper and longer-term appraisal of what is possible to achieve. 

PMID- 25971238
TI  - Psychometric properties of the stagnation scale in medication overuse headache
      patients.
AB  - BACKGROUND: Medication-overuse headache (MOH) is often comorbid with emotional
      disturbances, contributing to poorer outcomes. The aims of the present study were
      to assess the psychometric properties of the Stagnation Scale in a sample of MOH
      patients, and to compare two factor models: a three-factor model reported in
      previous studies and a proposed bi-factor model. METHODS: Consecutive adult
      outpatients (N = 310) admitted to the Regional Referral Headache Centre of the
      Sant'Andrea Hospital in Rome (Italy) were administered the Stagnation Scale and
      two questionnaires measuring depression and perceived disability. RESULTS: The
      original three-factor model demonstrated an adequate fit to the data (chi(2)(101)
      = 238.70; p < 0.001; Root Mean Square Error of Approximation [RMSEA] = 0.07; 90%
      CI of RMSEA = 0.06 / 0.08; Comparative Fit Index [CFI] = 0.98; Weighted Root Mean
      Square Residual [WRMR] = 0.75). However, the bi-factor model had a comparable or
      even better fit, with a RMSEA of 0.05 (90% CI: 0.04 / 0.07), providing strong
      evidence for an absolute fit to the data (chi(2)(88) = 161.43; p < 0.001; RMSEA =
      0.05; 90% CI of RMSEA = 0.04 / 0.07; CFI = 0.99; WRMR = 0.56). The stagnation
      general factor and all the group factors correlated significantly and positively
      with convergent measures. CONCLUSIONS: There is support for the use of the
      Stagnation Scale in MOH patients, with the goal of better understanding the role
      of psychological factors in the evolution and course of the disorder.

PMID- 25971239
TI  - About stagnation and the emperor's new clothes.
AB  - Innamorati and colleagues (Innamorati et al., J Headache Pain 16:2, 2015)
      validated the "stagnation scale" and proposed to use it to screen for
      psychopathology. I have some critical comments to consider about the theoretical
      and clinical value of the instrument. First, items of the scale are not specific,
      and may equally well measure worry, self-worth and distress. Second,
      questionnaires are tools to assess the experiences of patients, but not
      hypothesized causal processes. The scale can thus not identify patients who
      repress emotions. Third, the routine use of this instrument will detract
      clinicians from what really is at stake in patients and what may help them. 

PMID- 25971240
TI  - Reduced graphene oxide-ZnO self-assembled films: tailoring the visible light
      photoconductivity by the intrinsic defect states in ZnO.
AB  - ZnO is a wide direct bandgap semiconductor; its absorption can be tuned to the
      visible spectral region by controlling the intrinsic defect levels. Combining
      graphene with ZnO can improve its performance by photo-induced charge separation
      by ZnO and electronic transport through graphene. When reduced graphene oxide-ZnO
      is prepared by a hydrothermal method, the photophysical studies indicate that
      oxygen vacancy defect states are healed out by diffusion of oxygen from GO to ZnO
      during its reduction. Because of the passivation of oxygen vacancies, the visible
      light photoconductivity of the hybrid is depleted, compared to pure ZnO. In order
      to overcome this reduction in photocurrent, a photoelectrode is fabricated by
      layer-by-layer (LBL) self-assembly of ZnO and reduced graphene oxide. The
      multilayer films are fabricated by the electrostatic LBL self-assembly technique
      using negatively charged poly(sodium 4-styrene sulfonate)-reduced graphene oxide
      (PSS-rGO) and positively charged polyacrylamide-ZnO (PAM-ZnO) as building blocks.
      The multilayer films fabricated by this technique will be highly
      interpenetrating; it will enhance the interaction between the ZnO and rGO
      perpendicular to the electrode surface. Upon illumination under bias voltage
      defect assisted excitation occurs in ZnO and the photogenerated charge carriers
      can transfer to graphene. The electron transferred to graphene sheets can
      recombine in two ways; either it can recombine with the holes in the valence band
      of ZnO in its bilayer or the ZnO in the next bilayer. This type of tunnelling of
      electrons from graphene to the successive bilayers will result in efficient
      charge transfer. This transfer and propagation of electron will enhance as the
      number of bilayers increases, which in turn improve the photocurrent of the
      multilayer films. Therefore this self-assembly technique is an effective approach
      to fabricate semiconductor-graphene films with excellent conductivity. 

PMID- 25971241
TI  - [Endo-exo prostheses following limb-amputation].
AB  - BACKGROUND AND OBJECTIVE: Rehabilitation of patients having undergone limb
      amputation is difficult due to problems related to poor socket fit, which often
      deteriorates comfort, gait and the ability to take part in everyday life and
      work. The endo-exo prosthesis has been an alternative provision for people having
      undergone lower limb amputation for reasons other than diabetes or peripheral
      vascular disease for more than 10 years. The system consists of an intramedullar,
      osseointegrated and skin perforating prosthesis, which is implanted in the
      remaining bone and has an abutment to allow the attachment of the external
      prosthetic part including the knee joint in the case of a trans-femoral
      amputation. The idea originates in findings of modern tooth-implantology and
      involves a two-step operation. This study focuses on one centre's experience with
      the endo-exo prostheses in Lubeck, Germany, to describe and discuss the
      reliability of this alternative treatment method after lower limb amputation.
      MATERIALS AND METHODS: This article presents the results of lower limb amputees
      operated on in Lubeck, Germany between 1999-2013. It focuses on theoretical
      aspects of osseointegration and different clinically-based findings using the
      endo-exo technique over the last decade. RESULTS: 74 lower-limb amputees were
      treated with an endo-exo prosthesis until December 2013. There were only 4
      verified intramedullar infections, yet there were many unplanned surgical
      revisions secondary to soft-tissue infections in the beginning. They were
      successfully encountered via clinically-based changes that were made concerning
      implant design, wound treatment and operative technique. CONCLUSIONS: Since 1990
      a few groups have developed an innovative method that provides an alternative to
      traditional socket-type prostheses. This involves a skeletally anchored device
      that is inserted into the remaining stump and provides osseointegration into the
      bone. The distal part of the implant protrudes transcutaneously and allows
      attachment to a prosthetic limb. This creates a hard point where the forces are
      transmitted through the skeleton with a more physiological pathway because the
      bone becomes the force carrier again, closer in biomechanics to an able-bodied
      person. With long-term numbers that show successful osseointegration for more
      than 10 years it is evident that obligate bacterial colonization does not
      necessarily lead to an intramedullar infection. Especially short stumps that are
      difficult to treat with a socket can be successfully fitted with an endo-exo
      prosthesis. Amputees who would otherwise be bound to a wheelchair due to their
      challenging situation should specifically be regarded as potential profiteers of
      this novel treatment option.

PMID- 25971242
TI  - [The importance of soft tissue stabilization in trans-femoral amputation].
AB  - Transfemoral amputations with more proximal amputation levels have the problem of
      secondary development into flexion and abduction contractures. This is induced by
      muscle imbalance, especially the loss of adductor muscle insertions when abductor
      muscle insertions are preserved. This causes considerable problems when fitting
      prosthetics. Myodesis with insertion of the distally detached adductor magnus
      muscle to the lateral femoral cortex, introduced here, results in a stronger
      stump with good muscle balance, and prosthetics fitting is significantly
      improved. 

PMID- 25971243
TI  - The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine:
      A Population Pharmacokinetic Analysis of the STOP-PD.
AB  - BACKGROUND AND OBJECTIVE: Clinical evidence and expert opinion support using a
      combination of an antipsychotic and an antidepressant when treating major
      depression with psychotic features. We characterized the impact of sertraline co
      administration on olanzapine clearance in psychotic depression using population
      pharmacokinetic methods. METHODS: The Study of Pharmacotherapy for Psychotic
      Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or
      olanzapine plus sertraline. Olanzapine was started at 2.5-5 mg/day and sertraline
      at 25-50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine
      and 200 mg/day for sertraline. Up to four olanzapine concentration samples were
      collected during the 12-week trial and 12-week continuation phase. We used NONMEM
      (Version VII) for population pharmacokinetic analysis, assessing effects of the
      covariates sex, African American origin, smoking, age, and sertraline co
      administration. RESULTS: Population pharmacokinetic analysis comprised 336
      samples from 175 individuals. The structural model published by Bigos et al. was
      sufficient to describe the olanzapine data adequately: a one-compartment model
      with first-order absorption and elimination, using an additive residual error
      structure with the absorption rate constant fixed to 0.5. Sertraline co
      administration significantly increased olanzapine apparent clearance (p < 0.005)
      by 25-35 % depending on the patient characteristics included. Male sex was
      associated with a significantly increased clearance. Age and race did not have a
      significant impact on clearance. CONCLUSIONS: Contrary to expectations from the
      knowledge of cytochrome P450 interactions, sertraline increased olanzapine
      apparent clearance. Plausible explanations include patients treated with
      sertraline having poorer adherence to olanzapine, or the impact of sertraline
      inhibition of transporters resulting in increased intracellular concentrations
      and thus access to metabolizing enzymes.

PMID- 25971244
TI  - A multi-centre, randomised controlled trial of the effectiveness of PDSAFE to
      prevent falls among people with Parkinson's: study protocol.
AB  - BACKGROUND: Falls amongst people with Parkinson's (PwP) result in significant
      disability and reduced quality of life. There is emerging evidence that exercise
      based and physiotherapeutic interventions are of benefit for improving fall risk
      factors, such as balance. However, the benefit, in terms of preventing falls, is
      mixed. The development of effective interventions has been identified as the
      highest research priority for this population. The aim of this trial is to
      establish the effectiveness and cost-effectiveness of a novel, home-based
      physiotherapy programme, compared with usual care, on falls amongst PwP.
      METHODS/DESIGN: A UK multi-centre, community-based, single blind, randomised
      controlled trial with twelve month follow-up, and nested economic evaluation and
      qualitative studies will be undertaken. Six hundred PwP who live in their own
      home, have had one or more falls in the previous year and an MMSE score of >=24
      will be recruited. Those living in care homes and those needing assistance from
      another person to walk indoors will not be eligible. The intervention is a
      physiotherapist delivered, individually tailored and progressive, home-based
      programme (PDSAFE) comprising task orientated movement strategy training,
      functional lower limb strengthening and balance training, of six months duration.
      Unsupervised daily home exercises and strategies will be practised and supported
      using technology. Control participants will receive usual care. Data collection
      will include falls, cognitive state, balance and mobility, fear of falling,
      freezing of gait, mood, quality of life, carer quality of life and resource use.
      Data will be collected at baseline, three, six and twelve months. Longitudinal
      semi-structured interviews will be undertaken with forty participants to explore
      the expectations and experiences of participants. The primary outcome is risk of
      repeat falling at six months post-randomisation. DISCUSSION: The aims of this
      trial are to establish the effectiveness and cost-effectiveness of a novel, home
      delivered physiotherapy intervention (PDSAFE) compared with usual care on risk of
      falling for PwP who have a history of falling. PDSAFE is a novel intervention
      that builds upon the existing literature and targeting known risk factors, being
      the first study that uses a novel delivery modus (technology) in conjunction with
      traditional physiotherapeutic approaches. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN48152791.

PMID- 25971245
TI  - Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial
      correction after AAV gene therapy.
AB  - Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation
      in the enzyme beta-N-acetylhexosaminidase. Children with infantile onset SD
      develop seizures, loss of motor tone and swallowing problems, eventually reaching
      a vegetative state with death typically by 4years of age. Other symptoms include
      vertebral gibbus and cardiac abnormalities strikingly similar to those of the
      mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired
      catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like
      features of the feline SD model, we utilized radiography, MRI, echocardiography,
      histopathology and GAG quantification of both central nervous system and
      peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and
      structural abnormalities, skeletal changes and spinal cord compression that are
      consistent with accumulation of GAGs, but are much less prominent than the severe
      neurologic disease that defines the humane endpoint (4.5+/-0.5months). Sixteen
      weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat
      cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney,
      spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time
      and therefore may become a significant source of pathology in humans whose lives
      are substantially lengthened by gene therapy or other novel treatments for the
      primary, neurologic disease. 

PMID- 25971246
TI  - Folkbotanical classification: morphological, ecological and utilitarian
      characterization of plants in the Napf region, Switzerland.
AB  - BACKGROUND: Discussions surrounding ethnobiological classification have been
      broad and diverse. One of the recurring questions is whether classification is
      mainly based on the "inherent structure of biological reality" or on cultural,
      especially utilitarian needs. So far, studies about ethnobotanical classification
      have mainly been done in indigenous societies. Comparable data from
      industrialized countries are scarce. In this paper, folkbotanical classification
      data from the Napf region in central Switzerland is analysed and cross-culturally
      compared. METHODS: Structured and semi-structured interviews were conducted with
      60 adults and children chosen by random sampling. Descriptive statistics, t-tests
      and cultural domain analysis were used to analyze the data. RESULTS: Close to 500
      folk taxa have been documented during field work. As life-form taxa appeared
      tree, bush, grass, herb, flower, and mushroom. Intermediate taxa mentioned
      regularly were sub-categories of the life form tree and bush, i.e. conifer,
      deciduous tree, fruit tree, stone fruits, pomaceous fruits, and berry bush. The
      rank of the folk generic was by far the largest with 316 taxa (85.4%
      monotypical). The specific rank contained 145 taxa, the varietal 14 taxa. The 475
      generic, specific and varietal folk taxa could be assigned to 298 wild growing
      plant species, which make up 28.13% of the local flora, and to 213 cultivated
      plant species, subspecies and cultivars. Morphology, mainly life-form, fruits,
      leaves, and flowers, was the most important criterion for classifying plants.
      Other important criteria were their use (mainly edibility) and habitat (mainly
      meadow, forest and garden). The three criteria emerged spontaneously out of open
      questioning. CONCLUSION: The classification system of the Napf region is
      comparable to classification systems of indigenous societies, both in its shallow
      hierarchical structure and in the amount of recognized taxa. The classification
      of plants was mainly guided by morphology, habitat and use. The three aspects
      seem to be mutually linked for certain plant groups, which results in always the
      same groups, independent from the different sorting criteria. Sensory perception
      allows for a broader explanation of the known coincidence of morphology and use
      groups.

PMID- 25971247
TI  - Consumption of apples is associated with a better diet quality and reduced risk
      of obesity in children: National Health and Nutrition Examination Survey (NHANES)
      2003-2010.
AB  - BACKGROUND: Most children do not meet the recommendation for fruit consumption.
      Apples are the second most commonly consumed fruit in the US; however, no studies
      have examined the association of total apple products, apples, apple sauce, and
      100 % apple juice consumption on diet quality and weight/adiposity in children.
      METHODS: The purpose of this study was to examine the association between various
      apple consumption forms with diet quality and weight/adiposity in a nationally
      representative sample of children. Participants were children 2-18 years of age
      (N = 13,339) from the National Health and Nutrition Examination Survey 2003-2010.
      Intake was determined using a single interview administered 24-h diet recall.
      Apple product consumption was determined using the cycle-appropriate USDA Food
      and Nutrient Database for Dietary Studies food codes. Total diet quality and
      component scores were determined using the Healthy Eating Index-2010 (HEI).
      Anthropometrics were determined using standard methods. Covariate adjusted linear
      and logistic regressions were used to compare apple product consumers with non
      consumers; sample weights were used. Probability was set at <0.01. RESULTS:
      Approximately 26 % of the population (n = 3,482) consumed some form of apple
      products. Consumers of apple products, whole apples, apple sauce, and 100 % apple
      juice had higher HEI scores than non-consumers: 50.4 +/- 0.4 v 41.9 +/- 0.3, 52.5
      +/- 0.5 v 42.7 +/- 0.3, 52.1 +/- 0.8 v 47.2 +/- 0.4, and 51.4 +/- 0.6 v 46.5 +/-
      0.4, respectively. Apple products and whole apple consumers had lower BMI z
      scores than non-consumers: 0.4 +/- 0.04 v 0.5 +/- 0.03 and 0.3 +/- 0.1 v 0.5 +/-
      0.02, respectively. Apple products and whole apple consumers were 25 % (0.59-0.95
      99(th) CI) and 30 % (0.52-0.95 99(th) CI), respectively, were less likely to be
      obese than non-consumers. CONCLUSIONS: Consumption of any form of apples
      contributed to the fruit recommendation of children and improved diet quality.
      Apples should be included in the diets of children as a component of an overall
      healthy diet.

PMID- 25971248
TI  - Developing and refining the methods for a 'one-stop shop' for research evidence
      about health systems.
AB  - BACKGROUND: Policymakers, stakeholders and researchers have not been able to find
      research evidence about health systems using an easily understood taxonomy of
      topics, know when they have conducted a comprehensive search of the many types of
      research evidence relevant to them, or rapidly identify decision-relevant
      information in their search results. METHODS: To address these gaps, we developed
      an approach to building a 'one-stop shop' for research evidence about health
      systems. We developed a taxonomy of health system topics and iteratively refined
      it by drawing on existing categorization schemes and by using it to categorize
      progressively larger bundles of research evidence. We identified systematic
      reviews, systematic review protocols, and review-derived products through
      searches of Medline, hand searches of several databases indexing systematic
      reviews, hand searches of journals, and continuous scanning of listservs and
      websites. We developed an approach to providing 'added value' to existing content
      (e.g., coding systematic reviews according to the countries in which included
      studies were conducted) and to expanding the types of evidence eligible for
      inclusion (e.g., economic evaluations and health system descriptions). Lastly, we
      developed an approach to continuously updating the online one-stop shop in seven
      supported languages. RESULTS: The taxonomy is organized by governance, financial,
      and delivery arrangements and by implementation strategies. The 'one-stop shop',
      called Health Systems Evidence, contains a comprehensive inventory of evidence
      briefs, overviews of systematic reviews, systematic reviews, systematic review
      protocols, registered systematic review titles, economic evaluations and costing
      studies, health reform descriptions and health system descriptions, and many
      types of added-value coding. It is continuously updated and new content is
      regularly translated into Arabic, Chinese, English, French, Portuguese, Russian,
      and Spanish. CONCLUSIONS: Policymakers and stakeholders can now easily access and
      use a wide variety of types of research evidence about health systems to inform
      decision-making and advocacy. Researchers and research funding agencies can use
      Health Systems Evidence to identify gaps in the current stock of research
      evidence and domains that could benefit from primary research, systematic
      reviews, and review overviews.

PMID- 25971249
TI  - Effect of chromium supplementation on glycated hemoglobin and fasting plasma
      glucose in patients with diabetes mellitus.
AB  - AIMS: Chromium (Cr) is a trace element involved in glucose homeostasis. We aim to
      evaluate and quantify the effects of Cr supplementation on A1C and FPG in
      patients with T2DM. MATERIALS AND METHODS: A systematic literature search of
      Pubmed, EMBASE and the Cochrane Library (from database inception to 11/2014) with
      no language restrictions sought RCTs or cohort studies evaluating Cr
      supplementation in T2DM vs control and reporting either change in glycated
      hemoglobin (A1C) or fasting plasma glucose (FPG). Meta-analysis was conducted on
      each subtype of Cr supplement separately, and was analyzed by random effects
      model to yield the weighted mean differences (WMD) and 95% confidence intervals
      (CIs). Heterogeneity was assessed by using the I(2) statistic. RESULTS: A total
      of 14 RCTs (n=875 participants, mean age range: 30 to 83 years old, 8 to 24 weeks
      of follow-up) were identified (Cr chloride: n=3 study, Cr picolinate: n=5 study,
      brewer's yeast: n=4 study and Cr yeast: n=3 study). Compared with placebo, Cr
      yeast, brewer's yeast and Cr picolinate did not show statistically significant
      effects on A1C. Furthermore, compared to control, Cr chloride, Cr yeast and Cr
      picolinate showed no effect on FPG, however, brewer's yeast showed a
      statistically significant decrease in FPG -19.23 mg/dL (95% CI=-35.30 to -3.16,
      I(2)=21%, n=137). CONCLUSIONS: Cr supplementation with brewer's yeast may provide
      marginal benefits in lowering FPG in patients with T2DM compared to placebo
      however it did not have any effect on A1C.

PMID- 25971250
TI  - Extended varenicline treatment in a severe cardiopathic cigarette smoker: a case
      report.
AB  - INTRODUCTION: Tobacco smoking is the leading cause of cardiovascular morbidity
      and mortality and quitting tobacco use should be fundamental for cardiovascular
      patients. Varenicline is a smoking cessation pharmacological therapy able to
      improve the possibilities to successfully achieve this result. In 2011 the US
      Food and Drug Administration issued a safety announcement that varenicline may be
      associated with an increased risk of certain cardiovascular adverse events in
      patients who have cardiovascular disease. Following studies found no significant
      increase in cardiovascular serious adverse events associated with varenicline.
      For the first time in the literature, we describe the case of a cardiopathic hard
      smoker who received varenicline for 9 months without any side effect. By
      describing this case we want to underline the safety of varenicline, to
      illustrate the setting and the method that we used to support him and to
      underline the importance of promoting smoking cessation in heart patients. CASE
      PRESENTATION: Varenicline was used to promote smoking cessation in a 52-year-old
      Caucasian man who smoked 40 cigarettes per day, despite two ischemic
      cardiovascular events. He asked for a consultation in a pharmacy's smoking
      cessation service and after the assessment phase varenicline was prescribed. Due
      to his difficulty to quit smoking and given his good tolerance of the drug, we
      extended the treatment with varenicline to 9 months in order to achieve and
      maintain a complete smoking abstinence; intensive behavioural counselling was
      combined with the pharmacological therapy. By using exhaled carbon monoxide
      measurement we assessed smoking abstinence up to 2 years. CONCLUSIONS: The use of
      varenicline for a period longer than 6 months has not been described in the
      literature, particularly in heart patients. The extended varenicline therapy was
      clinically monitored and allowed the patient to consolidate his abstinence; the
      intensive behavioural counselling helped him to overcome his strong psychological
      dependence. Promoting smoking cessation in people who have cardiovascular disease
      is crucial. Currently available medications, such as varenicline, increase the
      chances of success and the risk of possible side effects is outweighed by the
      lifetime benefits and we hope that clinicians use them more frequently and
      confidently.

PMID- 25971251
TI  - The effect of anaesthetist grade and frequency of insertion on epidural failure:
      a service evaluation in a United Kingdom teaching hospital.
AB  - BACKGROUND: Despite being a commonly performed procedure, epidural catheter
      insertion has a significant failure rate. There is a lack of guidance as to how
      regularly the procedure should be performed in order to maintain competence. This
      study aimed to quantify whether increasing frequency of practice is associated
      with a reduction in failure rates. METHODS: Data were collected prospectively on
      all patients undergoing intra-abdominal or thoraco-abdominal surgery who received
      epidural analgesia as part of their post-operative analgesic regimen over a 36
      month period. Records were examined to identify the reason for epidural catheter
      removal, classified according to standardised definitions, the seniority of the
      inserting anaesthetist, and whether or not they were a permanent member of the
      anaesthetic department. Data were analysed using independent t tests, Mann
      Whitney tests and Fisher's test. RESULTS: 881 epidurals were inserted during the
      study period. 48 hour failure rate was 27.2%, whilst by 96 hours 33.9% of
      epidurals had failed. Increasing frequency of epidural insertion did not show a
      significant decrease in failure rate at either 48 (p = 0.36) or 96 hours (p =
      0.28). However, long-term survival of epidurals at 96 hours was greater if
      inserted by permanent rather than temporary members of staff (non-permanent
      60/141, 42.6% vs permanent 228/715, 31.9%, OR 1.58 (CI 1.09-2.29) p = 0.02).
      CONCLUSION: This study demonstrates that failure rates for postoperative epidural
      analgesia in major surgery are not dependent upon the frequency with which
      practitioners insert epidural catheters. However, failure rates are dependent on
      permanency of anaesthetic staff. These findings are significant when placed in
      the context of the General Medical Council's requirements for clinicians to
      maintain competence in their clinical practice, suggesting that institutional
      factors may have greater bearing on epidural success or failure than frequency of
      task performance.

PMID- 25971252
TI  - Transplantation of human oligodendrocyte progenitor cells in an animal model of
      diffuse traumatic axonal injury: survival and differentiation.
AB  - INTRODUCTION: Diffuse axonal injury is an extremely common type of traumatic
      brain injury encountered in motor vehicle crashes, sports injuries, and in
      combat. Although many cases of diffuse axonal injury result in chronic
      disability, there are no current treatments for this condition. Its basic lesion,
      traumatic axonal injury, has been aggressively modeled in primate and rodent
      animal models. The inexorable axonal and perikaryal degeneration and
      dysmyelination often encountered in traumatic axonal injury calls for
      regenerative therapies, including therapies based on stem cells and precursors.
      Here we explore the proof of concept that treatments based on transplants of
      human oligodendrocyte progenitor cells can replace or remodel myelin and,
      eventually, contribute to axonal regeneration in traumatic axonal injury.
      METHODS: We derived human oligodendrocyte progenitor cells from the human
      embryonic stem cell line H9, purified and characterized them. We then
      transplanted these human oligodendrocyte progenitor cells into the deep
      sensorimotor cortex next to the corpus callosum of nude rats subjected to
      traumatic axonal injury based on the impact acceleration model of Marmarou. We
      explored the time course and spatial distribution of differentiation and
      structural integration of these cells in rat forebrain. RESULTS: At the time of
      transplantation, over 90 % of human oligodendrocyte progenitor cells expressed
      A2B5, PDGFR, NG2, O4, Olig2 and Sox10, a profile consistent with their progenitor
      or early oligodendrocyte status. After transplantation, these cells survived well
      and migrated massively via the corpus callosum in both injured and uninjured
      brains. Human oligodendrocyte progenitor cells displayed a striking preference
      for white matter tracts and were contained almost exclusively in the corpus
      callosum and external capsule, the striatopallidal striae, and cortical layer 6.
      Over 3 months, human oligodendrocyte progenitor cells progressively matured into
      myelin basic protein(+) and adenomatous polyposis coli protein(+)
      oligodendrocytes. The injured environment in the corpus callosum of impact
      acceleration subjects tended to favor maturation of human oligodendrocyte
      progenitor cells. Electron microscopy revealed that mature transplant-derived
      oligodendrocytes ensheathed host axons with spiral wraps intimately associated
      with myelin sheaths. CONCLUSIONS: Our findings suggest that, instead of
      differentiating locally, human oligodendrocyte progenitor cells migrate massively
      along white matter tracts and differentiate extensively into ensheathing
      oligodendrocytes. These features make them appealing candidates for cellular
      therapies of diffuse axonal injury aiming at myelin remodeling and axonal
      protection or regeneration.

PMID- 25971253
TI  - Urothelial cancer gene regulatory networks inferred from large-scale RNAseq, Bead
      and Oligo gene expression data.
AB  - BACKGROUND: Urothelial pathogenesis is a complex process driven by an underlying
      network of interconnected genes. The identification of novel genomic target
      regions and gene targets that drive urothelial carcinogenesis is crucial in order
      to improve our current limited understanding of urothelial cancer (UC) on the
      molecular level. The inference of genome-wide gene regulatory networks (GRN) from
      large-scale gene expression data provides a promising approach for a detailed
      investigation of the underlying network structure associated to urothelial
      carcinogenesis. METHODS: In our study we inferred and compared three GRNs by the
      application of the BC3Net inference algorithm to large-scale transitional cell
      carcinoma gene expression data sets from Illumina RNAseq (179 samples), Illumina
      Bead arrays (165 samples) and Affymetrix Oligo microarrays (188 samples). We
      investigated the structural and functional properties of GRNs for the
      identification of molecular targets associated to urothelial cancer. RESULTS: We
      found that the urothelial cancer (UC) GRNs show a significant enrichment of
      subnetworks that are associated with known cancer hallmarks including cell cycle,
      immune response, signaling, differentiation and translation. Interestingly, the
      most prominent subnetworks of co-located genes were found on chromosome regions
      5q31.3 (RNAseq), 8q24.3 (Oligo) and 1q23.3 (Bead), which all represent known
      genomic regions frequently deregulated or aberated in urothelial cancer and other
      cancer types. Furthermore, the identified hub genes of the individual GRNs, e.g.,
      HID1/DMC1 (tumor development), RNF17/TDRD4 (cancer antigen) and CYP4A11
      (angiogenesis/ metastasis) are known cancer associated markers. The GRNs were
      highly dataset specific on the interaction level between individual genes, but
      showed large similarities on the biological function level represented by
      subnetworks. Remarkably, the RNAseq UC GRN showed twice the proportion of
      significant functional subnetworks. Based on our analysis of inferential and
      experimental networks the Bead UC GRN showed the lowest performance compared to
      the RNAseq and Oligo UC GRNs. CONCLUSION: To our knowledge, this is the first
      study investigating genome-scale UC GRNs. RNAseq based gene expression data is
      the data platform of choice for a GRN inference. Our study offers new avenues for
      the identification of novel putative diagnostic targets for subsequent studies in
      bladder tumors.

PMID- 25971254
TI  - Predictors of health-related quality of life in stroke patients after
      neurological inpatient rehabilitation: a prospective study.
AB  - BACKGROUND: The goal of the study was to investigate the long-term course of
      health-related quality of life (HRQoL) in stroke survivors during and up to 2.5
      years after inpatient neurological rehabilitation and to identify predictors of
      HRQoL. METHODS: HRQoL was determined in 152 stroke survivors in a single-centre
      prospective cohort study at four time points: upon admission to inpatient
      rehabilitation, at discharge, and one and 2.5 years after discharge. Their HRQoL
      was determined by administering the EQ-5D at all four measurement points. During
      inpatient rehabilitation, the SF-36 was administered in addition to the EQ-5D.
      Predictors were identified through multiple regression analysis. RESULTS: During
      inpatient rehabilitation, the "European Index" of the EQ-5D rose significantly (p
      < 0.001) from 45.4 to 66.7. The change in HRQoL on the SF-36 was convergent. The
      HRQoL of the stroke patients living at home remained at the same level for 2.5
      years following discharge. In the multiple regression analysis, the EQ-5D Index
      at discharge (p = 0.049), the risk of falls as defined by Runge and Rehfeld (p =
      0.001), and the change in emotional quality of life on the SF-36 during inpatient
      rehabilitation (p = 0.048) predicted HRQoL 2.5 years following discharge.
      CONCLUSION: On the basis of our results, we conclude that the long-term health
      related quality of life of stroke survivors can be positively influenced by
      reducing the risk of falls and improving emotional well-being during neurological
      inpatient rehabilitation.

PMID- 25971255
TI  - Differential glucocorticoid metabolism in patients with persistent versus
      resolving inflammatory arthritis.
AB  - INTRODUCTION: Impairment in the ability of the inflamed synovium to generate
      cortisol has been proposed to be a factor in the persistence and severity of
      inflammatory arthritis. In the inflamed synovium, cortisol is generated from
      cortisone by the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme.
      The objective of this study was to determine the role of endogenous
      glucocorticoid metabolism in the development of persistent inflammatory
      arthritis. METHODS: Urine samples were collected from patients with early
      arthritis (symptoms <=12 weeks duration) whose final diagnostic outcomes were
      established after clinical follow-up and from patients with established
      rheumatoid arthritis (RA). All patients were free of disease-modifying anti
      rheumatic drugs at the time of sample collection. Systemic measures of
      glucocorticoid metabolism were assessed in the urine samples by gas
      chromatography/mass spectrometry. Clinical data including CRP and ESR were also
      collected at baseline. RESULTS: Systemic measures of 11beta-HSD1 activity were
      significantly higher in patients with early arthritis whose disease went on to
      persist, and also in the subgroup of patients with persistent disease who
      developed RA, when compared with patients whose synovitis resolved over time. We
      observed a significant positive correlation between systemic 11beta-HSD1 activity
      and ESR/CRP in patients with established RA but not in any of the early arthritis
      patients group. CONCLUSIONS: The present study demonstrates that patients with a
      new onset of synovitis whose disease subsequently resolved had significantly
      lower levels of systemic 11beta-HSD1 activity when compared with patients whose
      synovitis developed into RA or other forms of persistent arthritis. Low absolute
      levels of 11beta-HSD1 activity do not therefore appear to be a major contributor
      to the development of RA and it is possible that a high total body 11beta-HSD1
      activity during early arthritis may reduce the probability of disease resolution.

PMID- 25971256
TI  - Efficient and Inducible Use of Artificial MicroRNAs in Marchantia polymorpha.
AB  - We describe the efficient use of artificial microRNAs (amiRs) in Marchantia
      polymorpha using both endogenous and heterologous primary microRNA (pri-miR)
      hairpin backbones. Targeting of two transcription factor genes, MpARF1 and MpRR
      B, mediating different hormonal responses, demonstrated that amiRs can create
      specific and reproducible physiological and morphological defects, facilitating
      interpretation of gene function. A third amiR was designed to target a gene
      encoding a component of the Polycomb recessive complex 2, MpE(z), and
      constitutive expression of this amiR results in sporeling lethality. Adaptation
      of an estrogen-inducible system allowed analysis of the phenotypic effects of
      induction of this amiR during other stages of the life cycle. We discuss the
      advantages and challenges of the use of amiRs as a tool for reverse genetic
      analysis in M. polymorpha. 

PMID- 25971257
TI  - A Systems Approach to Elucidate Heterosis of Protein Abundances in Yeast.
AB  - Heterosis is a universal phenomenon that has major implications in evolution and
      is of tremendous agro-economic value. To study the molecular manifestations of
      heterosis and to find factors that maximize its strength, we implemented a large
      scale proteomic experiment in yeast. We analyzed the inheritance of 1,396
      proteins in 55 inter- and intraspecific hybrids obtained from Saccharomyces
      cerevisiae and S. uvarum that were grown in grape juice at two temperatures. We
      showed that the proportion of heterotic proteins was highly variable depending on
      the parental strain and on the temperature considered. For intraspecific hybrids,
      this proportion was higher at nonoptimal temperature. Unexpectedly, heterosis for
      protein abundance was strongly biased toward positive values in interspecific
      hybrids but not in intraspecific hybrids. Computer modeling showed that this
      observation could be accounted for by assuming concave relationships between
      protein abundances and their controlling factors, in line with the metabolic
      model of heterosis. These results point to nonlinear processes that could play a
      central role in heterosis. 

PMID- 25971259
TI  - Many fixed dose drug combinations for sale in India are not approved.

PMID- 25971258
TI  - In-vitro diagnosis of single and poly microbial species targeted for diabetic
      foot infection using e-nose technology.
AB  - BACKGROUND: Effective management of patients with diabetic foot infection is a
      crucial concern. A delay in prescribing appropriate antimicrobial agent can lead
      to amputation or life threatening complications. Thus, this electronic nose (e
      nose) technique will provide a diagnostic tool that will allow for rapid and
      accurate identification of a pathogen. RESULTS: This study investigates the
      performance of e-nose technique performing direct measurement of static headspace
      with algorithm and data interpretations which was validated by Headspace SPME-GC
      MS, to determine the causative bacteria responsible for diabetic foot infection.
      The study was proposed to complement the wound swabbing method for bacterial
      culture and to serve as a rapid screening tool for bacteria species
      identification. The investigation focused on both single and poly microbial
      subjected to different agar media cultures. A multi-class technique was applied
      including statistical approaches such as Support Vector Machine (SVM), K Nearest
      Neighbor (KNN), Linear Discriminant Analysis (LDA) as well as neural networks
      called Probability Neural Network (PNN). Most of classifiers successfully
      identified poly and single microbial species with up to 90% accuracy.
      CONCLUSIONS: The results obtained from this study showed that the e-nose was able
      to identify and differentiate between poly and single microbial species
      comparable to the conventional clinical technique. It also indicates that even
      though poly and single bacterial species in different agar solution emit
      different headspace volatiles, they can still be discriminated and identified
      using multivariate techniques.

PMID- 25971260
TI  - Support for Fathers of Children With Heart Defects.
AB  - The purpose of the study was to illuminate the meanings of the lived experiences
      of support as disclosed by fathers of children with congenital heart defect
      (CHD). Narrative interviews were conducted individually with five fathers of
      children diagnosed with CHD. A phenomenological-hermeneutic method was used to
      interpret the verbatim transcribed narrative interviews. The meanings of the
      lived experiences of support for the fathers were identified in two themes and
      illustrate the fathers' feelings of being supported when being in a mutual
      relationship with others. A third theme illustrates the situation when support is
      absent. Our findings indicate that support for fathers of children with CHD might
      be best promoted by the philosophy of family-centered care. 

PMID- 25971261
TI  - Serum and cellular ribavirin pharmacokinetic and concentration-effect analysis in
      HCV patients receiving sofosbuvir plus ribavirin.
AB  - OBJECTIVES: Ribavirin concentrations may impact hepatitis C virus (HCV) treatment
      outcome. We modelled ribavirin serum and intracellular ribavirin monophosphate
      (RBV-MP) and ribavirin triphosphate (RBV-TP) pharmacokinetics in red blood cells
      (RBC) using samples collected during the NIAID SPARE trial to explore
      associations with treatment outcome and the development of anaemia. PATIENTS AND
      METHODS: Individuals infected with HCV genotype 1 (GT1) received 400 mg of
      sofosbuvir and either low-dose or weight-based ribavirin as part of the NIAID
      SPARE trial. Concentrations were modelled using NONMEM and associated with
      treatment outcomes using unpaired t-tests or Pearson's rho correlations. RESULTS:
      Average day 14 RBV-MP concentrations were higher in subjects with haemoglobin
      nadir <10 g/dL relative to patients with haemoglobin nadir >=10 g/dL (6.54 versus
      4.48 pmol/10(6) cells; P = 0.02). Additionally, day 14 RBV-MP average
      concentrations trended towards being higher in subjects that achieved sustained
      virological response (SVR) as compared with patients who relapsed (4.97 versus
      4.09 pmol/10(6) cells; P = 0.07). Receiver operating characteristic curves
      suggested day 14 RBV-MP concentration thresholds of 4.4 pmol/10(6) cells for SVR
      (P = 0.06) and 6.1 pmol/10(6) cells for haemoglobin nadir <10 versus >=10 g/dL (P
      = 0.02), with sensitivity and specificity >=60%. Dosing simulations showed that
      800 mg of ribavirin once daily produced day 14 RBV-MP concentrations within the
      4.4-6.1 pmol/10(6) cells range. CONCLUSIONS: RBV-MP concentrations in RBC at day
      14 were related to anaemia and SVR. A therapeutic range was identified for RBV-MP
      in persons with HCV GT1 disease receiving 24 weeks of sofosbuvir plus ribavirin,
      suggesting a potential pharmacological basis for individualized ribavirin dosing
      in IFN-free regimens.

PMID- 25971263
TI  - Effect of Prematurity on Cerebellar Growth.
AB  - The aim of this study was to evaluate cerebellar growth of preterm infants.
      Vermis height and transverse cerebellar diameter were measured by cranial
      ultrasonography in 38 preterm infants (27-32 weeks) at birth and term equivalent
      age. Measurements were compared with 40 term appropriate-for-gestational-age
      infants. Preterms at term equivalent age had larger vermis height than term
      infants (2.39 +/- 0.25 cm vs 2.25 +/- 0.18 cm, P = .005), whereas no significant
      difference was found in the transverse cerebellar diameter (5.32 +/- 0.38 cm vs
      5.44 +/- 0.23 cm, P = .13). Vermis height and transverse cerebellar diameter of
      appropriate-for-gestational-age preterm infants (n = 29) were found larger than
      small-for-gestational-age ones (n = 9). Vermis height and transverse cerebellar
      diameter at term equivalent age of appropriate-for-gestational-age preterm
      infants born before and after 29 weeks of age showed no significant difference.
      Cerebellar growth is preserved in extreme preterms. However, being small for
      gestational age may have deleterious effects on cerebellar development. 

PMID- 25971262
TI  - Acceptability and feasibility of HIV self-testing among men who have sex with men
      in Peru and Brazil.
AB  - HIV self-testing has the potential to increase testing frequency and uptake. This
      pilot study assessed the feasibility and acceptability of HIV self-testing in a
      sample of sexually active men who have sex with men (MSM) in Peru and Brazil.
      Participants were trained to use a whole blood rapid HIV self-test and instructed
      to use the self-test monthly during this three-month study. Test acceptability
      was measured with self-reported use of the test at the one-month and three-month
      study visits, and test feasibility was assessed by direct observation of self
      test administration at the final three-month visit. A total of 103 participants
      (52 in Peru and 51 in Brazil) were enrolled, and 86% completed the three-month
      study. Nearly all participants reported use of the self-test (97% at one-month
      and 98% at three-month visit), and all participants correctly interpreted the
      self-administered test results when observed using the test at the final study
      visit. HIV self-testing with a blood-based assay was highly acceptable and
      feasible. HIV self-testing may have the potential to increase testing frequency
      and to reach high-risk MSM not currently accessing HIV-testing services.

PMID- 25971265
TI  - [Roles of mTORC1 in acute myeloid leukemia].
AB  - Constitutive activation of mTOR is associated with acceleration of leukemia
      development. However, mTORC1 functions in established leukemia are unclear. We
      evaluated the role of mTORC1 in mouse acute myeloid leukemia (AML) cells using a
      murine model of conditional deletion of Raptor, an essential component of mTORC1,
      and an MLL-AF9-driven leukemia model. mTORC1 is essential for leukemia
      initiation, but a subset of AML cells with undifferentiated phenotypes survived
      long-term in the absence of mTORC1 activity. Our study demonstrated AML cells
      lacking mTORC1 activity to be capable of self-renewal as AML stem cells. This
      review will summarize our study on the roles of mTORC1 in AML, and discuss
      potential benefits and risks of mTORC2 inhibition and the potential use of mTOR
      inhibitors as AML therapy. 

PMID- 25971266
TI  - [Comparison of the incidence and trends of hematologic malignancies between Japan
      and the United States].
AB  - The incidence of a malignant disease reflects both genetics and the cumulative
      environmental exposures of a population. Therefore, evaluation of the incidence
      and trends of a disease in different populations may provide insights into its
      etiology and pathogenesis. To evaluate the incidence of hematologic malignancies
      according to specific subtypes, we used population-based registry data in Japan
      and the United States from 1993 to 2008. The age-adjusted incidence of
      hematologic malignancies in Japan was approximately one-half that in the United
      States but has been increasing significantly, whereas no significant change was
      seen in the United States (annual percent change: Japan, +2.4%; USA, +0.1%).
      Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) showed the largest incidence
      differences, with those of chronic lymphocytic leukemia, HL-nodular sclerosis,
      mycosis fungoides, and cutaneous T-cell lymphoma being the most remarkable.
      Differences in the incidence and trends for specific subtypes also showed a
      marked contrast across subtypes which, in turn, may provide novel and significant
      future insights into disease etiology. 

PMID- 25971267
TI  - [Maintenance of leukemic and normal hematopoietic stem cells in bone marrow
      niches by EVI1-regulated GPR56].
AB  - Acute myeloid leukemia (AML) with high ecotropic viral integration site-1 (EVI1)
      expression (EVI1high AML) is classified as a refractory leukemia with a poor
      prognosis. We identified G protein-coupled receptor 56 (GPR56) as a novel marker
      for EVI1high AML, which is an orphan adhesion G protein-coupled receptor (GPCR).
      GPR56 was found to be associated with high cell adhesion and anti-apoptotic
      activities in EVI1high AML through activation of RhoA signaling. Moreover, in
      Gpr56-/- mice, the number of hematopoietic stem cells (HSCs) in bone marrow was
      significantly decreased with proportional increases in the spleen and peripheral
      blood, reflecting extramedullary hematopoiesis. The number of Gpr56-/- HSC
      progenitor cells in the G0 phase was significantly reduced with impaired adhesion
      and the loss of GPR56 function, which diminished the in vivo repopulating ability
      of HSCs. In conclusion, GPR56 may represent an important GPCR for the maintenance
      of quiescence and cellular adhesion of EVI1high AML and HSCs in the bone marrow
      niche. Moreover, given that GPR56 expression in leukemia stem cells is much
      higher than that in HSCs, GPR56 is a candidate therapeutic target for leukemia
      stem cells in EVI1high AML.

PMID- 25971268
TI  - [NF-kappaB activity in myeloid leukemia stem cells].
AB  - Acute myeloid leukemia (AML) is a hematologic malignancy which originates from
      leukemia initiating cells (LICs). Since LICs are considered to be resistant to
      standard chemotherapy, the identification of common mechanisms involved in LIC
      maintenance and progression is crucial to establishing broadly effective
      therapeutic agents for AML. The NF-kappaB pathway is one of the most promising
      targets, considering that its constitutive activation has been reported in
      different types of AML. In myeloid leukemia mouse models, we found that NF-kappaB
      activity is maintained specifically in LICs through autocrine TNF-alpha
      secretion, forming an NF-kappaB/TNF-alpha positive feedback loop. LICs had
      increased levels of active proteasome machinery, which promoted the degradation
      of IkappaBalpha and further supported NF-kappaB activity. Genetic ablation of TNF
      alpha or NF-kappaB markedly suppressed leukemia progression in vivo. These
      findings demonstrate that NF-kappaB/TNF-alpha signaling in LICs contributes to
      leukemia progression and provide a widely applicable approach for targeting LICs.

PMID- 25971269
TI  - [Analysis of prognostic factors in transplant-eligeble newly diagnosed myeloma
      patients treated with bortezomib plus dexamethasone as induction therapy].
AB  - We retrospectively analyzed, and herein discuss, the outcomes of and prognostic
      factors for 35 untreated multiple myeloma patients less than 65 years of age who
      received induction therapies with bortezomib (Bor) and dexamethasone (BD) for the
      purpose of up-front autologous peripheral blood stem cell transplantation (SCT).
      The overall response rate was 77% (27 cases, including 4 [11%] complete response
      and 13 [37%] very good partial response cases). The rate of SCT accomplishment
      was 51% (18 cases). The 3 year-progression free survival (PFS) rate for the SCT
      group was significantly higher than that of the non-SCT group (41% vs 0%,
      P=0.0037). This result reflects the significantly more severe adverse effects of
      induction therapy for the non-SCT than the SCT group. Among reasons for SCT drop
      out, 29% of cases suffered severe peripheral neuropathy with features such as
      irreversible numbness and pain. The analysis of PFS revealed a cytogenetic
      factor, favorable chromosomal type at diagnosis, to predict a better outcome (P
      values on univariate and multivariate analyses were 0.0004 and 0.0405,
      respectively). Our observations suggest establishment of induction therapy, aimed
      at reducing adverse effects and overcoming unfavorable cytogenetic abnormalities,
      to be necessary for improving the outcomes of patients with multiple myeloma. 

PMID- 25971270
TI  - [Multiple myeloma recurring as small intestinal polyposis after autologous
      hematopoietic stem cell transplantation].
AB  - A 52-year-old woman was diagnosed with BJP-lambda multiple myeloma (MM) in
      November 2012. She was treated with six cycles of bortezomib and dexamethasone,
      resulting in a very good partial response. The patient underwent autologous
      peripheral blood stem cell transplantation (PBSCT) 6 months after the diagnosis,
      and clearly achieved a complete response thereafter. She again suffered chronic
      abdominal pain with spontaneous remission 9 months after the PBSCT, and, 2 months
      thereafter, was hospitalized due to intestinal obstruction. Two small intestinal
      intussusceptions and polyposis in the small intestine were found on abdominal
      computed tomography. As conservative treatment produced no improvement, partial
      resection of the small intestine was performed. The pathologic review clearly
      demonstrated the polyps to have atypical plasma cell infiltrates in the mucosa of
      the small intestine involving all layers. Immunohisto-chemistry and FISH analyses
      yielded positive results for CD138, CD79a, and lambda light chain, consistent
      with extramedullary relapse of MM. It is very rare for MM to present with
      polyposis in the small intestine. There have been no reports describing such a
      case after autologous PBSCT. 

PMID- 25971271
TI  - [Chromosomally integrated human herpesvirus-6 requiring differential diagnosis of
      reactivation after allogeneic hematopoietic stem cell transplantation].
AB  - Human herpesvirus-6 (HHV-6) is known to cause critical encephalitis, as a central
      nervous system infection, in some hematopoietic stem cell transplantation (HSCT)
      recipients. Chromosomally integrated human herpesvirus-6 (CIHHV-6) persistently
      shows HHV-6 DNA in blood, but this does not necessarily suggest active infection.
      The true clinical significance in HSCT is not clear. The prevalence of CIHHV-6 in
      Japan is reportedly 0.21%. We herein report two HSCTs: from a CIHHV-6-positive
      donor to a negative recipient and from a negative donor to a positive recipient.
      In the CIHHV-6-positive donor case, the recipient's plasma, which had been
      negative for HHV-6 before HSCT, became positive after transplantation and the
      level then remained high, although the subject was asymptomatic. In the CIHHV-6
      positive recipient case, the patient's plasma viral load was high just after
      transplantation, although the subject was asymptomatic, and the load gradually
      decreased after engraftment. Antivirals had no effect on the viral load in either
      case. We should consider CIHHV-6 when the HHV-6 DNA load in blood persists
      asymptomatically after HSCT, to avoid misdiagnosis of reactivated HHV-6 infection
      and overuse of antivirals. It is also useful to monitor HHV-6 DNA in blood before
      HSCT, to distinguish HHV-6 reactivation from CIHHV-6. 

PMID- 25971273
TI  - [Efficacy of serum immunoglobulin free light chain and 18F-FDG PET/CT for
      therapeutic evaluation in a case with multiple plasmacytoma of bone].
AB  - Solitary/multiple plasmacytoma of bone, a rare disease as compared to multiple
      myeloma, is characterized by monoclonal proliferation of plasma cells in local
      legion (s) of bone, with no bone marrow abnormalities. Monoclonal
      gammagloblinemia is often absent in these conditions, and useful examinations
      allowing evaluation of responses to treatment are as yet lacking. Recently, 18F
      FDG PET/CT (PET/CT) was reported to be useful for detecting bone lesions. PET/CT
      is also valuable for predicting the outcomes of patients with solitary
      plasmacytoma, when applied in combination with the serum free light chain (sFLC)
      kappa/lambda ratio. We present a 62-year-old male with multiple plasmacytoma of
      bone (MPB), in whom PET/CT and the sFLC kappa/lambda ratio were useful for
      evaluating the response to treatment. The patient was diagnosed with MPB, with
      PET/CT showing multiple abnormal tracer uptakes in the scapula, spine, and ribs.
      The sFLC ratio was markedly elevated, with the kappa chain level being especially
      high. We administered bortezomib and dexamethasone, after which the abnormal
      uptakes on PET/CT disappeared. The sFLC ratio and the FLC value also normalized,
      and have remained stable for more than one year, to date, since treatment. In our
      case, PET/CT and the sFLC kappa/lambda ratio were found to be extremely useful
      for monitoring treatment responses.

PMID- 25971272
TI  - [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic
      syndrome after allogeneic hematopoietic cell transplantation].
AB  - Myelodysplastic syndrome (MDS) is known to often be complicated by a range of
      autoimmune diseases. We herein present a case with MDS complicated by cold
      autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She
      was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May
      2009. In January 2010, she underwent unrelated allogeneic bone marrow
      transplantation but was re-admitted in October 2010 for treatment of relapsed
      MDS. Despite daily transfusions of red blood cells, her anemia failed to improve.
      Her laboratory examinations showed a low haptoglobin level and elevation of
      indirect bilirubin and LDH. The direct Coombs test was positive at a low and at
      room temperature and cold agglutinin was negative. After confirming the diagnosis
      of cold AIHA, all transfusion fluids were warmed but her anemia still failed to
      improve. In addition to the warmed transfusion fluids, we administered
      corticosteroids, immunosuppressive agents and high-dose intravenous
      immunoglobulin infusions. This management strategy ameliorated the patient's
      hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare.
      Our patient thus provides a valuable contribution to medical knowledge. 

PMID- 25971274
TI  - [Successful management of orthopedic operations requiring general anesthesia in a
      PNH patient after introduction of eculizumab].
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem
      cell disorder that presents with hemolytic anemia, thrombosis, and bone marrow
      failure. Stressors such as infection and pregnancy have been known to exacerbate
      hemolysis in PNH patients. Surgery can also trigger prominent complement
      activation and is an important risk factor for hemolysis. Furthermore, the
      postoperative thrombosis risk is high. Eculizumab, which is a humanized
      monoclonal antibody against C5, suppresses hemolysis and prevents thrombosis, and
      thus improves quality of life for PNH patients. However, few reports have focused
      on eculizumab-treated PNH patients undergoing surgery. We report a 79-year-old
      PNH patient receiving eculizumab treatment who underwent three consecutive
      orthopedic surgeries requiring general anesthesia. Perioperative management was
      carried out routinely, as in non-PNH patients, and no postoperative complications
      developed. Surgery was formerly considered to be a high risk event for PNH
      patients, but this case raises the possibility that even elderly PNH patients may
      undergo surgery safely when maintained on eculizumab treatment. 

PMID- 25971275
TI  - [Successful treatment with pseudo-autologous blood stem cell transplantation for
      an adolescent-onset multiple myeloma who relapsed after allogenic bone marrow
      transplantation].
AB  - A 14-year-old male with multiple myeloma (IgG-lambda, ISS stage 3) received
      myeloablative matched unrelated bone marrow transplantation, and achieved a
      complete response. At 16 months after the transplantation, he relapsed. The
      relapse was resistant to bortezomib and thalidomide. Peripheral blood showed
      mixed chimerism with 10% recipient cells. Peripheral blood stem cells (PBSC) were
      collected and pseudo-autologous PBSC transplantation (PASCT) was performed
      following high-dose melphalan without graft-versus-host disease prophylaxis.
      Hematopoietic recovery was prompt and a partial response was obtained without
      graft-versus-host disease exacerbation. We have presented a rare case of
      adolescent-onset multiple myeloma, obtaining a transient response with PASCT
      following post-allogeneic transplant relapse. 

PMID- 25971278
TI  - [Can a sensitizer potency be attenuated?].

PMID- 25971279
TI  - Loss of ATRX, associated with DNA methylation pattern of chromosome end, impacted
      biological behaviors of astrocytic tumors.
AB  - Loss of ATRX leads to epigenetic alterations, including abnormal levels of DNA
      methylation at repetitive elements such as telomeres in murine cells. We
      conducted an extensive DNA methylation and mRNA expression profile study on a
      cohort of 82 patients with astrocytic tumors to study whether ATRX expression was
      associated with DNA methylation level in astrocytic tumors and in which cellular
      functions it participated. We observed that astrocytic tumors with lower ATRX
      expression harbored higher DNA methylation level at chromatin end and astrocytic
      tumors with ATRX-low had distinct gene expression profile and DNA methylation
      profile compared with ATRX-high tumors. Then, we uncovered that several ATRX
      associated biological functions in the DNA methylation and mRNA expression
      profile (GEP), including apoptotic process, DNA-dependent positive regulation of
      transcription, chromatin modification, and observed that ATRX expression was
      companied by MGMT methylation and expression. We also found that loss of ATRX
      caused by siRNA induced apoptotic cells increasing, reduced tumor cell
      proliferation and repressed the cell migration in glioma cells. Our results
      showed ATRX-related regulatory functions of the combined profiles from DNA
      methylation and mRNA expression in astrocytic tumors, and delineated that loss of
      ATRX impacted biological behaviors of astrocytic tumor cells, providing important
      resources for future dissection of ATRX role in glioma.

PMID- 25971280
TI  - Inference of Evolutionary Forces Acting on Human Biological Pathways.
AB  - Because natural selection is likely to act on multiple genes underlying a given
      phenotypic trait, we study here the potential effect of ongoing and past
      selection on the genetic diversity of human biological pathways. We first show
      that genes included in gene sets are generally under stronger selective
      constraints than other genes and that their evolutionary response is correlated.
      We then introduce a new procedure to detect selection at the pathway level based
      on a decomposition of the classical McDonald-Kreitman test extended to multiple
      genes. This new test, called 2DNS, detects outlier gene sets and takes into
      account past demographic effects and evolutionary constraints specific to gene
      sets. Selective forces acting on gene sets can be easily identified by a mere
      visual inspection of the position of the gene sets relative to their two
      dimensional null distribution. We thus find several outlier gene sets that show
      signals of positive, balancing, or purifying selection but also others showing an
      ancient relaxation of selective constraints. The principle of the 2DNS test can
      also be applied to other genomic contrasts. For instance, the comparison of
      patterns of polymorphisms private to African and non-African populations reveals
      that most pathways show a higher proportion of nonsynonymous mutations in non
      Africans than in Africans, potentially due to different demographic histories and
      selective pressures. 

PMID- 25971282
TI  - Spontaneous electrical activities at myofascial trigger points at different
      stages of recovery from injury in a rat model.
AB  - BACKGROUND: Spontaneous electrical activity (SEA) is a feature of myofascial
      trigger points (MTrPs), which can either be latent or active. However, SEA at
      different stages of recovery from MTrPs remains unclear. OBJECTIVE: To
      investigate the temporal changes in the nature of SEA after generation of MTrPs
      in a rat model. METHODS: 32 rats were divided into four groups: 24 rats were
      assigned to experimental groups (EGs), which underwent the MTrP modelling
      intervention and 8 were allocated to a control group (CG). All EG rats received a
      blunt strike to the left vastus medialis combined with eccentric exercise for 8
      weeks. After modelling, the EG rats were subdivided into three groups with total
      recovery times of 4, 8 and 12 weeks (EG-4w, EG-8w and EG-12w, respectively). Taut
      bands (TBs) with and without the presence of active MTrPs were identified in the
      left hind limb muscles of all rats, verified by SEA and further examined with
      electromyography recordings. Myoelectrical signals were also categorised into one
      of five types. RESULTS: CG rats had fewer TBs than EG rats and EGs showed
      variable frequencies of SEA. SEA frequencies were higher in EG-4w than in EG-8w
      and EG-12w groups (240.57+/-72.9 vs 168.14+/-64.5 and 151.63+/-65.4,
      respectively, p<0.05) and were significantly greater in all EGs than in the CG
      (55.75+/-21.9). Relative to CG rats, amplitudes and durations of electrical
      potentials in the EG were only increased in the EG-8w and EG-12w groups. Types IV
      and V myoelectrical signals were never seen in latent MTrPs and type V signals
      did not occur in EG-4w rats. CONCLUSIONS: Increasing recovery periods following a
      MTrP modelling intervention in rats are characterised by different frequencies
      and amplitudes of SEA from TBs. TRIAL REGISTRATION NUMBER: 2014012.

PMID- 25971281
TI  - Global Shifts in Genome and Proteome Composition Are Very Tightly Coupled.
AB  - The amino acid composition (AAC) of proteomes differs greatly between
      microorganisms and is associated with the environmental niche they inhabit,
      suggesting that these changes may be adaptive. Similarly, the oligonucleotide
      composition of genomes varies and may confer advantages at the DNA/RNA level.
      These influences overlap in protein-coding sequences, making it difficult to
      gauge their relative contributions. We disentangle these effects by
      systematically evaluating the correspondence between intergenic nucleotide
      composition, where protein-level selection is absent, the AAC, and ecological
      parameters of 909 prokaryotes. We find that G + C content, the most frequently
      used measure of genomic composition, cannot capture diversity in AAC and across
      ecological contexts. However, di-/trinucleotide composition in intergenic DNA
      predicts amino acid frequencies of proteomes to the point where very little cross
      species variability remains unexplained (91% of variance accounted for).
      Qualitatively similar results were obtained for 49 fungal genomes, where 80% of
      the variability in AAC could be explained by the composition of introns and
      intergenic regions. Upon factoring out oligonucleotide composition and
      phylogenetic inertia, the residual AAC is poorly predictive of the microbes'
      ecological preferences, in stark contrast with the original AAC. Moreover, highly
      expressed genes do not exhibit more prominent environment-related AAC signatures
      than lowly expressed genes, despite contributing more to the effective proteome.
      Thus, evolutionary shifts in overall AAC appear to occur almost exclusively
      through factors shaping the global oligonucleotide content of the genome. We
      discuss these results in light of contravening evidence from biophysical data and
      further reading frame-specific analyses that suggest that adaptation takes place
      at the protein level. 

PMID- 25971283
TI  - Intra-abdominal pressure, Cardiac Index and vascular resistance during
      hyperthermic intraperitoneal chemotherapy: a prospective observational study.
AB  - BACKGROUND: Increased intra-abdominal pressure and hemodynamic variations during
      hyperthermic intraperitoneal chemotherapy (HIPEC) are expected to be comparable
      to pneumoperitoneum with decreased Cardiac Index (CI) and increased Systemic
      Vascular Resistance Index (SVRI). We hypothesized that despite comparable
      increased intra-abdominal pressure, hemodynamic changes during HIPEC would
      substantially differ from those described in laparoscopic surgery. METHODS: In
      this prospective observational clinical study, after obtaining written informed
      consent, we assessed intra-abdominal pressure and hemodynamic and respiratory
      changes during HIPEC in 10 consecutive patients. Intra-abdominal pressure as the
      primary endpoint was continuously measured with a catheter placed in the
      abdominal cavity. Secondary endpoints were hemodynamic changes measured by pulse
      contour analysis and respiratory alterations. Fluid management was based on
      stroke volume variation. RESULTS: The mean intra-abdominal pressure was
      constantly elevated during HIPEC at a level of 14.2 mmHg (P=0.002 compared to
      baseline). The mean SVRI dropped from 1716 dyn*sec/cm3/m2 to 1490 dyn*sec/cm5/m2
      at the end of HIPEC (P<0.05). Mean CI increased from 3.2 to 3.45 L/m2 (P<0.001)
      and Horovitz index decreased from 548 to 380 (P=0.001). Median fluid intake was
      7000 mL. No patient developed acute kidney injury. CONCLUSIONS: Increased intra
      abdominal pressure during HIPEC was comparable to pneumoperitoneum. Hemodynamic
      changes however were opposed with a decrease in SVRI and a compensative increase
      in CI. Current guidelines for anesthetic management in patients undergoing HIPEC
      are mainly based on findings from laparoscopic surgery and should therefore be
      reconsidered critically.

PMID- 25971284
TI  - Plasma-Lyte or Hartmann's for major liver resection: which is the best solution?

PMID- 25971286
TI  - Arrhythmogenic right ventricular cardiomyopathy and sports activity.

PMID- 25971287
TI  - PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present,
      and the future.
AB  - Reduction in low-density lipoprotein cholesterol (LDL-C), mainly with statins,
      has decreased the risk of cardiovascular events over the last few decades.
      However, there are several patient populations that warrant further decrease in
      LDL-C by additional cholesterol-lowering therapy other than statins. Proprotein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of drugs
      that have been shown to further decrease LDL-C by 50-70% when administered as a
      monotherapy or on a background therapy with statins. Proprotein convertase
      subtilisin/kexin type 9 inhibitors are also an excellent example of drug
      development in which discovery of gene mutations and its clinical effects have
      rapidly progressed into successful preclinical and clinical studies with multiple
      Phases 1-3 clinical trials completed or ongoing to date. This review summarizes
      the rapid evolution of the drug from genetic discovery to identification of
      targets for the drugs, to animal and human testing, and to large clinical
      outcomes trials, followed by discussion on foreseeable challenges of PCSK9
      inhibitors. 

PMID- 25971289
TI  - Annals of Palliative Medicine is indexed in PubMed.

PMID- 25971288
TI  - Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a
      subgroup analysis of the ENGAGE AF-TIMI 48 trial.
AB  - BACKGROUND: In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE)
      regimen had a similar incidence of ischaemic stroke compared with warfarin,
      whereas a higher incidence was observed with the lower-dose regimen (LDE).
      Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The
      current pre-specified exploratory analysis was performed to determine the effect
      of amiodarone on the relative efficacy and safety profile of edoxaban. METHODS
      AND RESULTS: At randomization, 2492 patients (11.8%) were receiving amiodarone.
      The primary efficacy endpoint of stroke or systemic embolic event was
      significantly lower with LDE compared with warfarin in amiodarone treated
      patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence
      intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P
      interaction <0.01). In patients randomized to HDE, no such interaction for
      efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P
      interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95%
      CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR
      0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when
      compared with warfarin, independent of amiodarone use. CONCLUSIONS: Patients
      randomized to the LDE treated with amiodarone at the time of randomization
      demonstrated a significant reduction in ischaemic events vs. warfarin when
      compared with those not on amiodarone, while preserving a favourable bleeding
      profile. In contrast, amiodarone had no effect on the relative efficacy and
      safety of HDE.

PMID- 25971290
TI  - Surgical palliation for malignant disease requiring locoregional control.
AB  - BACKGROUND: Surgical palliation of cancer is best defined as procedures performed
      with non-curative intent to improve quality of life or control symptoms of
      advanced malignancy. Soft tissue involvement of advanced malignancies may produce
      symptoms such as pain, bleeding, or odor that significantly reduce quality of
      life. Literature on outcomes of palliative resection of soft tissue malignancy
      for local or regional control is lacking. METHODS: Soft tissue resections
      performed with palliative intent for locoregional control were identified from a
      prospectively maintained palliative surgery database at a tertiary care center
      from January 2004 to July 2013. Tumor type, presenting symptom, procedure
      performed, and symptom recurrence were recorded. Patients were followed for at
      least 60 days or until death. RESULTS: Thirty-one patients who underwent
      palliative soft tissue resection for local control were identified. Primary tumor
      types included melanoma (n=9, 29.0%), squamous cell carcinoma (n=9, 29.0%),
      sarcoma (n=5, 16.1%), breast (n=3, 9.7%), and other (n=5, 16.1%). Eighteen of 31
      patients (58.1%) underwent resection for pain, two (6.5%) for bleeding, and
      eleven (35.5%) for local control or other symptoms. Procedures were performed on
      the trunk (n=17, 54.8%), extremities (n=7, 22.6%), head/neck (n=5, 16.1%), or
      multiple areas (n=2, 6.5%). Eleven of 31 patients (35.5%) underwent axillary,
      inguinal, or neck lymph node dissection, seventeen (54.8%) radical resection, and
      three (9.7%) wound excision. Split-thickness skin graft was performed in 6 of 17
      radical resections (35.3%). Five patients (16.1%) had symptom recurrence at the
      site of the initial palliative procedure, of whom four (12.9%) underwent a second
      palliative procedure. Seven patients (22.6%) had new disease-related symptoms
      develop during follow-up. Thirty-day morbidity was 29.0%; mortality was 3.2%,
      which was associated with progression of disease. CONCLUSIONS: Palliative surgery
      for local control of advanced soft tissue malignancy can provide durable symptom
      relief and improved quality of life. These procedures positively impact patients
      regardless of primary tumor type or tumor extent. Careful patient selection is
      important in order to maximize benefit of surgical palliation and minimize
      morbidity and mortality.

PMID- 25971291
TI  - A values-based conceptual framework for surgical appropriateness: an illustrative
      case report.
AB  - Appropriateness in surgical decision-making necessitates that surgical treatments
      are aligned with patients' goals and values for care. To arrive at informed
      decisions for surgery, patients must have an understanding of post-operative
      recovery, the impact on quality of life, and expected functional outcomes. This
      article describes an illustrative case of an older patient who experienced a
      decline in health, functional status, and quality of life in the months following
      a major surgical operation that was not clearly aligned with her personal goals
      and priorities. Palliative care needs that arose during the course of the
      patient's treatment are identified and described, revealing opportunities for
      better integration between palliative and postoperative care. A conceptual
      framework for measuring appropriateness in surgery, which incorporates patients'
      goals, values and preferences for medical treatments, is proposed. 

PMID- 25971292
TI  - Whole brain radiotherapy for patients with poor prognosis: possibilities for the
      impact of the QUARTZ trial.

PMID- 25971293
TI  - The End of Life Nursing Education Nursing Consortium project.
AB  - In 2000, the City of Hope Medical Center and the American Association of Colleges
      of Nursing (AACN) developed the End-of-Life Nursing Education Consortium (ELNEC)
      Core curriculum to educate nurses and other healthcare professionals on end of
      life care, so that attention to the dying could be improved and their unique
      needs addressed. Since its inception, over 19,500 nurses and other professionals
      have attended the ELNEC train-the-trainer courses. Upon course completion, the
      participants, often nurse educators, returned to their schools, healthcare
      systems, and communities and introduced the ELNEC content into nursing curricula,
      annual competencies, and new employee orientation. In 2005, the national ELNEC
      Project Team concluded that an international curriculum should be developed. The
      first ELNEC International course was launched in 2006 in Salzburg, Austria. Since
      that time, trainers have come from 85 countries world-wide, and the curriculum
      has been translated into eight languages. In 2015, three international courses
      will be presented: in Beijing, China, Kipkaren, Kenya, and Salzburg, Austria. 

PMID- 25971294
TI  - Retrospective review of the incidence of monitoring blood glucose levels in
      patients receiving corticosteroids with systemic anticancer therapy.
AB  - BACKGROUND: Corticosteroids are used adjuvant to certain chemotherapy regimens,
      either as an antiemetic, to reduce other side effects, or to enhance cancer
      treatment. Additionally, they are frequently used for symptom control in cancer
      patients with end stage disease. Corticosteroid use may induce hyperglycemia in
      approximately 20-50% of patients, which may negatively affect patient outcomes.
      OBJECTIVE: To determine the frequency of blood glucose monitoring in patients
      with and without diabetes receiving continuous corticosteroids with chemotherapy,
      and to determine the incidence of treatment-emergent abnormal blood glucose
      levels and steroid-induced diabetes mellitus (DM). METHODS: A retrospective
      review was conducted for 30 genitourinary (GU) cancer patients who were treated
      with continuous oral corticosteroids as part of their chemotherapy regimen. The
      Canadian Diabetes Association (CDA) criterion for diagnosis of diabetes was
      applied to categorize patients into two distinct groups, patients with diabetes
      and patients without diabetes. This categorization was made based on glucose
      measurements completed prior to commencement of corticosteroid therapy. Glucose
      monitoring was defined as receiving a laboratory blood glucose test before first
      chemotherapy administration along with a test within a week of each subsequent
      treatment cycle. The CDA criteria for diagnosis of pre-diabetes and diabetes was
      used to classify glucose levels as hyperglycemic. RESULTS: The mean incidence of
      blood glucose monitoring was 19% and 76% in patients with diabetes and patients
      without diabetes, respectively. Approximately, 40% of patients with diabetes
      required an adjustment to their diabetes management and a further 20% required
      hospitalization. Fifteen patients without diabetes received a fasting blood
      glucose test, of which 40% had abnormal blood glucose results; half of these fell
      into the pre-diabetic range and half in the diabetic range. Ten patients without
      diabetes were tested for diabetes using the CDA criteria for diabetes diagnosis
      during or after their chemotherapy, of which 30% developed diabetes. CONCLUSIONS:
      In order to optimize patient care, blood glucose levels should be monitored in
      all patients receiving continuous oral corticosteroids as part of their
      chemotherapy. Future studies should be conducted prospectively to determine the
      most effective manner of monitoring in order to implement screening guidelines
      and avoid unnecessary morbidity.

PMID- 25971296
TI  - Improved Immunoassay Sensitivity in Serum as a Result of Polymer-Entrapped
      Quantum Dots: 'Papaya Particles'.
AB  - Fluorescent labels are widely employed in biomarker quantification and
      diagnostics, however they possess narrow Stokes shifts and can photobleach,
      limiting multiplexed detection applications and compromising sensitivity. In
      contrast, quantum dots do not photobleach and have much wider Stokes shifts, but
      a paucity of robust surface attachment chemistries for bioconjugation has limited
      their uptake in biomedical diagnostics. We report a novel class of biofunctional
      fluorescent labels based on trapping of ~10(4) quantum dots within a core
      nanoparticle. The doped particles act as scaffolds for generation of a
      multilayered shell consisting of a functionalized hydrophilic polymer with
      covalently attached receptors for analyte capture. These constructs, which
      conceptually resemble a papaya fruit, are chemically stable, remain monodispersed
      for >6 months in buffer, and show utility in immunoassay applications. Using
      monoclonal antibody fragments against nonstructural protein dengue NS1, an early
      biomarker for dengue fever, antibody immobilization capacity was 75-fold higher
      compared with traditional carbodiimide protein coupling. In the model dengue
      immunoassay, we observed a 15-fold lower limit of detection and 4-fold higher
      fluorescence intensity with the "papaya particles" compared to current "best-in
      class" commercial reagents. Direct deployment in human serum allowed sensitive
      detection of different NS1 serotypes with lower limits of detection within the
      clinically relevant range (1-10 ng/mL), and sufficient specificity for
      identification of the dengue serotype was achieved for concentrations >10 ng/mL
      (DV1-3) and >50 ng/mL (DV4). The combination of chemical and physical stability
      and high binding capacity combined with the intrinsic advantages of quantum dots
      may enable more simple, robust diagnostic assays in the future. 

PMID- 25971297
TI  - Targeting Focal Adhesion Kinase and Resistance to mTOR Inhibition in Pancreatic
      Neuroendocrine Tumors.
AB  - BACKGROUND: Focal adhesion kinase (FAK) mediates survival of normal pancreatic
      islets through activation of AKT. Upon malignant transformation of islet cells
      into pancreatic neuroendocrine tumors (PanNETs), AKT is frequently overexpressed
      and mutations in the AKT/mTOR pathway are detected. Because mTOR inhibitors
      rarely induce PanNET tumor regression, partly because of feedback activation of
      AKT, novel combination strategies are needed to target FAK/AKT/mTOR signaling.
      METHODS: We characterized the activation of FAK in PanNETs using
      immunohistochemistry and Western blot analysis and tested the FAK inhibitor PF
      04554878 in human PanNET cells in vitro and in vivo (at least three mice per
      group). In addition, we evaluated the effect of combined FAK and mTOR inhibition
      on PanNET viability and apoptosis. All statistical tests were two-sided. RESULTS:
      We found that FAK is overexpressed and hyperphosphorylated in human PanNETs and
      that PF-04554878 strongly inhibited FAK (Tyr397) autophosphorylation in a dose
      dependent manner. We found that PF-04554878 inhibited cell proliferation and
      clonogenicity and induced apoptosis in PanNET cells. Moreover, oral
      administration of PF-04554878 statistically significantly reduced tumor growth in
      a patient-derived xenograft model of PanNET (P = .02) and in a human PanNET
      xenograft model of peritoneal carcinomatosis (P = .03). Importantly, PF-04554878
      synergized with the mTOR inhibitor everolimus by preventing feedback AKT
      activation. CONCLUSIONS: We demonstrate for the first time that FAK is
      overexpressed in PanNETs and that inhibition of FAK activity induces apoptosis
      and inhibits PanNET proliferation. We found that the novel FAK inhibitor PF
      04554878 synergizes with everolimus, a US Food and Drug Administration-approved
      agent for PanNETs. Our findings warrant the clinical investigation of combined
      FAK and mTOR inhibition in PanNETs.

PMID- 25971299
TI  - Challenges and opportunities in measuring cancer recurrence in the United States.
AB  - Cancer recurrence and disease-free survival are key outcomes for measuring the
      burden of illness, assessing the quality of cancer care, and informing decisions
      about increasingly costly cancer therapies. Yet information about recurrence is
      not collected in cancer registries or other population-based data sources. To
      address the lack of population-based recurrence information, researchers are
      increasingly using algorithms applied to health claims to infer recurrence.
      However, the validity of these approaches has not been comprehensively evaluated.
      In this commentary, we review existing studies and discuss options for improving
      the availability of recurrence data. We found that the validity of claims-based
      approaches appears promising in small, single institution studies, but larger
      population-based studies have identified substantial limitations with using
      claims to identify recurrence. With the increasing availability of health data,
      there are potential options that can be implemented to enhance information about
      recurrence. These options include design of software for the electronic medical
      record that enables rapid and standardized reporting of recurrence, use of
      electronic pathology reports to facilitate streamlined collection of recurrence
      by cancer registries, and mandates by insurers to require reporting of recurrence
      on health claims submitted by physicians. All of these options will require that
      governmental agencies, health insurers, professional societies, and other groups
      recognize the importance of population-based recurrence data and determine that
      this information is a priority for assessing cancer outcomes and costs. 

PMID- 25971298
TI  - The introduction of generic aromatase inhibitors and treatment adherence among
      Medicare D enrollees.
AB  - BACKGROUND: Aromatase inhibitors (AIs) substantially reduce breast cancer
      mortality in clinical trials, but high rates of nonadherence to these long-term
      oral therapies have reduced their impact outside of trials. We examined the
      association of generic AI availability with AI adherence among a large national
      breast cancer cohort. METHODS: Using a quasi-experimental prepost design, we
      examined the effect of generic AI introductions (7/2010 and 4/2011) on adherence
      among a national cohort of women with incident breast cancer in 2006 and 2007 who
      were enrolled in the Medicare D pharmaceutical coverage program. Medicare D
      claims were used to calculate AI adherence, defined as a medication possession
      ratio of 80% or more of eligible days, over 36 months. Multivariable logistic
      regression models estimated with generalized estimating equations were applied to
      longitudinal adherence data to control for possible confounders, including
      receipt of a Medicare D low-income subsidy, and to account for repeated measures.
      All statistical tests were two-sided. RESULTS: Sixteen thousand four hundred
      sixty-two Medicare D enrollees were eligible. Adherence declined throughout the
      study. However, among women without a subsidy, the median quarterly out-of-pocket
      cost of anastrozole fell from $183 in the fourth quarter of 2009 to $15 in 2011,
      and declines in adherence were attenuated with generic AI introductions.
      Regression-adjusted adherence probabilities were estimated to be 5.4% higher
      after generic anastrozole was introduced in 2010 and 11% higher after generic
      letrozole/exemestane was introduced in 2011. Subsidy recipients had higher
      adherence rates throughout the study. CONCLUSIONS: The introduction of generic
      medications attenuated the decline in adherence to AIs over three years of
      treatment among breast cancer survivors not receiving low-income subsidies for
      Medicare D coverage.

PMID- 25971300
TI  - FGL2 as a Multimodality Regulator of Tumor-Mediated Immune Suppression and
      Therapeutic Target in Gliomas.
AB  - BACKGROUND: Fibrinogen-like protein 2 (FGL2) may promote glioblastoma multiforme
      (GBM) cancer development by inducing multiple immune-suppression mechanisms.
      METHODS: The biological significance of FGL2 expression was assessed using the
      The Cancer Genome Atlast (TCGA) glioma database and tumor lysates analysis. The
      therapeutic effects of an anti-Fgl2 antibody and the role of immune suppression
      regulation by Fgl2 were determined in immune-competent, NOD-scid IL2Rgammanull
      (NSG), and FcgammaRIIB-/- mice (n = 3-18 per group). Data were analyzed with two
      way analysis of variance, log-rank survival analysis, and Pearson correlation.
      All statistical tests were two-sided. RESULTS: In low-grade gliomas, 72.5% of
      patients maintained two copies of the FGL2 gene, whereas 83.8% of GBM patients
      had gene amplification or copy gain. Patients with high levels of FGL2 mRNA in
      glioma tissues had a lower overall survival (P = .009). Protein levels of FGL2 in
      GBM lysates were higher relative to low-grade glioma lysates (11.48+/-5.75ng/mg
      vs 3.96+/-1.01ng/mg, P = .003). In GL261 mice treated with an anti-FGL2 antibody,
      median survival was 27 days compared with only 17 days for mice treated with an
      isotype control antibody (P = .01). The anti-FGL2 antibody treatment reduced
      CD39(+) Tregs, M2 macrophages, programmed cell death protein 1 (PD-1), and
      myeloid-derived suppressor cells (MDSCs). FGL2-induced increases in M2, CD39, and
      PD-1 were ablated in FcgammaRIIB-/- mice. CONCLUSIONS: FGL2 augments glioma
      immunosuppression by increasing the expression levels of PD-1 and CD39, expanding
      the frequency of tumor-supportive M2 macrophages via the FcgammaRIIB pathway, and
      enhancing the number of MDSCs and CD39(+) regulatory T cells. Collectively, these
      results show that FGL2 functions as a key immune-suppressive modulator and has
      potential as an immunotherapeutic target for treating GBM.

PMID- 25971301
TI  - Characterization and identification of the proteins bound to two types of
      polyhydroxyalkanoate granules in Pseudomonas sp. 61-3.
AB  - Pseudomonas sp. 61-3 accumulates two types of polyhydroxyalkanoates (PHAs),
      poly(3-hydroxybutyrate) [P(3HB)], and poly(3HB-co-3-hydroxyalkanoates) [P(3HB-co
      3HA)], and some proteins associated with their PHA granules have been identified.
      To date, PhaFPs (GA36) and PhaIPs (GA18) were identified from P(3HB-co-3HA)
      granules. In this study, the gene encoding GA24 associated with P(3HB) granule
      was identified as phbPPs. PhbPPs was composed of 192 amino acids with a
      calculated molecular mass of 20.4 kDa and was assumed to be a phasin. phbFPs gene
      and unknown ORF were also found on phb locus. PhbFPs was anticipated to be the
      transcriptional repressor of phbPPs gene. PhbPPs was bound to the P(3HB-co-3HA)
      granules with 3HB composition of more than 87 mol%, and PhaIPs and PhaFPs were
      bound to the P(3HB-co-3HA) granules with 3HA (C6-C12) composition of more than 13
      mol% in the producing cells, suggesting that localization of these proteins is
      attributed to the monomer compositions of the copolymers.

PMID- 25971302
TI  - Barriers and opportunities for enhancing patient recruitment and retention in
      clinical research: findings from an interview study in an NHS academic health
      science centre.
AB  - BACKGROUND: In the UK, the recruitment of patients into clinical research is a
      national health research and development policy priority. There has been limited
      investigation of how national level factors operate as barriers or facilitators
      to recruitment work, particularly from the perspective of staff undertaking
      patient recruitment work. The aim of this study is to identify and examine staff
      views of the key organisational barriers and facilitators to patient recruitment
      work in one clinical research group located in an NHS Academic Health Science
      Centre. METHODS: A qualitative study utilizing in-depth, one-to-one semi
      structured interviews with 11 purposively selected staff with particular
      responsibilities to recruit and retain patients as clinical research subjects.
      Thematic analysis classified interview data by recurring themes, concepts, and
      emergent categories for the purposes of establishing explanatory accounts.
      RESULTS: The findings highlight four key factors that staff perceived to be most
      significant for the successful recruitment and retention of patients in research
      and identify how staff located these factors within patients, studies, the
      research centre, the trust, and beyond the trust. Firstly, competition for
      research participants at an organisational and national level was perceived to
      undermine recruitment success. Secondly, the tension between clinical and
      clinical research workloads was seen to interrupt patient recruitment into
      studies, despite national funding arrangements to manage excess treatment costs.
      Thirdly, staff perceived an imbalance between personal patient burden and
      benefit. Ethical committee regulation, designed to protect patients, was
      perceived by some staff to detract from clarification and systematisation of
      incentivisation strategies. Finally, the structure and relationships within
      clinical research teams, in particular the low tacit status of recruitment
      skills, was seen as influential. CONCLUSIONS: The results of this case-study,
      conducted in an exemplary NHS academic research centre, highlight current
      systematic challenges to patient recruitment and retention in clinical studies
      more generally as seen from the perspective of staff at the 'sharp end' of
      recruiting. Staff experience is that, beyond individual clinical research design
      and protocol factors, wider organisational and extra-organisational norms,
      structures, and processes operate as significant facilitators or hindrances in
      the recruitment of patients as research subjects.

PMID- 25971303
TI  - Iterative and prolonged remission in metastatic breast cancer using pegylated
      irinotecan: a case report.
AB  - INTRODUCTION: Pegylated irinotecan NKTR-102 is a topoisomerase I inhibitor
      polymer conjugate. This new formulation of irinotecan has been evaluated in a
      phase II clinical trial and is showing remarkable activity. To the best of our
      knowledge, this is the first case report of an impressive iterative response to
      pegylated irinotecan NKTR-102 in metastatic breast cancer. CASE PRESENTATION: We
      report the case of a 49-year-old Caucasian woman diagnosed with metastatic
      luminal A breast cancer with initial bone followed by liver and bone marrow
      metastases, treated with three lines of hormonal therapy, targeted therapy and
      six lines of chemotherapy. She showed no major response to conventional
      treatment, whereas, the tumor shrinkage under pegylated irinotecan NKTR-102 was
      impressive, durable and iterative. CONCLUSIONS: Reintroduction of an active drug
      is a valid approach as illustrated by our case. The results of the current phase
      III trials of pegylated irinotecan NKTR-102 are eagerly awaited.

PMID- 25971304
TI  - Use-value and importance of socio-cultural knowledge on Carapa procera trees in
      the Sudanian zone in Mali.
AB  - BACKGROUND: Carapa procera is a native oil tree species with multipurpose values
      traditionally exploited by the local population in Southern Mali. This study
      focused on the assessment of local knowledge about the use of Carapa procera.
      METHODS: Semi-structured ethnobotanical questionnaires were conducted among the
      ethnic groups Senufo, Fulani and Bambara in two localities in the Sudanian zone
      in Mali. Use values among these ethnic groups and gender were evaluated. RESULTS:
      This study showed that Carapa procera is a species with multiple uses and high
      use values. According to the consensus value for plant parts (CPP), the nuts
      constituted 57% of exploited plant parts followed by bark and leaves (12%), wood
      and roots (7%), mistletoes (4%) and gum (1%). The use diversity (UD) values of
      Carapa procera showed a high proportion of cosmetic (UD = 0.49) and therapeutic
      (UD = 0.36) uses. The UD for therapeutic uses was higher for ethnic groups in
      Ziekorodougou than in Niankorobougou. In contrast, the UD for cosmetic uses was
      higher for ethnic groups in Niankorobougou than in Ziekorodougou. Comparative
      analysis between ethnic groups revealed that the highest UD for cosmetic uses
      (0.63) was observed in the Bambara ethnic group, whereas the highest UD for
      therapeutic uses (0.39) was obtained in the Senufo ethnic group. The UD showed
      that cosmetic uses were higher for women than for men in both locations. Men in
      Ziekorodougou had the highest level of knowledge regarding plant parts used,
      forms of use and the specific reasons for using Carapa procera. CONCLUSION: This
      study highlighted the sociocultural importance of Carapa procera. In the light of
      its multipurpose uses, the promotion and enhancement of Carapa procera can
      provide significant socio-economic benefits to local people. In this perspective,
      it is necessary to implement conservation strategies and sustainable management
      through domestication of the species.

PMID- 25971305
TI  - Gadolinium contrast-enhanced MRI reveals cystic lateral semicircular canal
      contents.
AB  - CONCLUSION: Contrast-enhanced magnetic resonance imaging (MRI) reveals variations
      in the endolymphatic morphology of the cystic lateral semicircular canal (CLSC)
      that correlate with inner ear function. This report is the first to suggest a
      relationship between the morphology and function of this common inner ear
      malformation in clinical cases. OBJECTIVES: This study investigated the
      radiological and functional findings of a common inner ear malformation using
      computed tomography (CT), gadolinium contrast-enhanced magnetic resonance imaging
      (MRI), caloric testing, and cervical and ocular vestibular evoked myogenic
      potential (VEMP) testing. METHOD: Four ears in three patients who were
      radiologically diagnosed with a CLSC and a normal cochlea on high-resolution CT
      and contrast-enhanced MRI were included. Semicircular canal and vestibular
      functions were analyzed using the caloric test and cervical and ocular VEMP
      testing. RESULTS: Unilateral and bilateral cystic canals were found in two and
      one patients, respectively. In the first patient, the malformed vestibule and
      cystic space were separate on imaging, and perilymph filled the cystic space. The
      functional test results were normal. In the second patient, endolymph filled both
      cystic spaces, and the functional responses were poor. In the third patient,
      endolymph filled the cystic space, and the ear did not respond during functional
      testing.

PMID- 25971306
TI  - Segmentation of MR image using local and global region based geodesic model.
AB  - BACKGROUND: Segmentation of the magnetic resonance (MR) images is fundamentally
      important in medical image analysis. Intensity inhomogeneity due to the unknown
      noise and weak boundary makes it a difficult problem. METHOD: The paper presents
      a novel level set geodesic model which integrates the local and the global
      intensity information in the signed pressure force (SPF) function to suppress the
      intensity inhomogeneity and implement the segmentation. First, a new local and
      global region based SPF function is proposed to extract the local and global
      image information in order to ensure a flexible initialization of the object
      contours. Second, the global SPF is adaptively balanced by the weight calculated
      by using the local image contrast. Third, two-phase level set formulation is
      extended to a multi-phase formulation to successfully segment brain MR images.
      RESULTS: Experimental results on the synthetic images and MR images demonstrate
      that the proposed method is very robust and efficient. Compared with the related
      methods, our method is much more computationally efficient and much less
      sensitive to the initial contour. Furthermore, the validation on 18 T1-weighted
      brain MR images (International Brain Segmentation Repository) shows that our
      method can produce very promising results. CONCLUSIONS: A novel segmentation
      model by incorporating the local and global information into the original GAC
      model is proposed. The proposed model is suitable for the segmentation of the
      inhomogeneous MR images and allows flexible initialization.

PMID- 25971307
TI  - Cost-utility analysis of percutaneous mitral valve repair in inoperable patients
      with functional mitral regurgitation in German settings.
AB  - BACKGROUND: To determine the cost-effectiveness of the percutaneous mitral valve
      repair (PMVR) using Carillon(r) Mitral Contour System(r) (Cardiac Dimensions
      Inc., Kirkland, WA, USA) in patients with congestive heart failure accompanied by
      moderate to severe functional mitral regurgitation (FMR) compared to the
      prolongation of optimal medical treatment (OMT). METHODS: Cost-utility analysis
      using a combination of a decision tree and Markov process was performed. The
      clinical effectiveness was determined based on the results of the Transcatheter
      Implantation of Carillon Mitral Annuloplasty Device (TITAN) trial. The mean age
      of the target population was 62 years, 77% of the patients were males, 64% of the
      patients had severe FMR and all patients had New York Heart Association
      functional class III. The epidemiological, cost and utility data were derived
      from the literature. The analysis was performed from the German statutory health
      insurance perspective over 10-year time horizon. RESULTS: Over 10 years, the
      total cost was ?36,785 in the PMVR arm and ?18,944 in the OMT arm. However, PMVR
      provided additional benefits to patients with an 1.15 incremental quality
      adjusted life years (QALY) and an 1.41 incremental life years. The percutaneous
      procedure was cost-effective in comparison to OMT with an incremental cost
      effectiveness ratio of ?15,533/QALY. Results were robust in the deterministic
      sensitivity analysis. In the probabilistic sensitivity analysis with a
      willingness-to-pay threshold of ?35,000/QALY, PMVR had a 84 % probability of
      being cost-effective. CONCLUSIONS: Percutaneous mitral valve repair may be cost
      effective in inoperable patients with FMR due to heart failure.

PMID- 25971308
TI  - Immediate and long-term efficacy of laterally-wedged insoles on persons with
      bilateral medial knee osteoarthritis during walking.
AB  - BACKGROUND: The current study aimed to investigate the immediate and long-term
      effects of laterally-wedged (LW) insoles on the knee loadings, the knee abductor
      moment (KAM) in particular, and the compensatory changes at other lower limb
      joints in patients with bilateral medial knee osteoarthritis during level walking
      with and without LW insoles. METHODS: Older adults with bilateral medial knee OA
      (age 66 +/- 5.3 years; height 156 +/- 4.9 cm; mass 60 +/- 5.1 kg; leg length
      83.72 +/- 3.64 cm) were studied using computerized gait analysis initially
      (Baseline) and 6 weeks after using LW insoles (Follow-up) during barefoot walking
      and walking with LW insoles (7 degrees  of lateral inclination, with medial arch
      support). The three-dimensional angles and internal moments at the lower limb
      joints, as well as the ground reaction forces, were obtained using a motion
      analysis system and two forceplates. Key features of all the variables were
      compared using paired t tests for immediate effects (barefoot vs. LW) and for
      long-term effects (Baseline vs. Follow-up). The symptomatic severity (WOMAC
      Index) was also evaluated (Baseline vs. Follow-up). RESULTS: The KAM with LW
      insoles at Baseline was significantly reduced when compared to the barefoot
      condition (p < 0.05), suggesting that the LW insoles were effective in reducing
      unfavorable loadings at the knee immediately upon wearing the insoles. After 6
      weeks of wearing LW insoles (Follow-up), no significant changes were found in
      most of the biomechanical variables, including KAM (p > 0.05), when compared to
      Baseline with LW insoles. However, a specific gait adaptation with reduced knee
      loading was revealed when walking without LW insoles, i.e., for the barefoot
      condition (p < 0.05). CONCLUSIONS: After long-term use of LW insoles, the pain
      and physical function were improved with decreased peak KAM. A specific gait
      adaptation with reduced KAM was also found when walking without LW insoles. These
      results indicate a positive long-term effect in persons with bilateral medial
      knee OA, both as an orthosis to assist walking, and as a treatment intervention
      to facilitate gait adaptations in favor of reduced KAM.

PMID- 25971309
TI  - NOB1 expression predicts early response to cisplatin-based chemotherapy in
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: The aim of this study was to investigate the predictive value of Nin
      one binding (NOB1) expression for response to cisplatin-based chemotherapy in
      patients with advanced non-small-cell lung cancer (NSCLC). METHODS: A total of
      105 consecutive patients with advanced NSCLC were retrospectively investigated
      between January 2012 and June 2014. We used transbronchial biopsy to collect
      cancer tissue samples. Immunohistochemistry were used in the detection of NOB1
      protein expression. We assessed the chemotherapy early response by response
      evaluation criteria in solid tumours (RECIST) Version 1.1 at the end of the
      second cycle of chemotherapy. RESULTS: In the 105 transbronchial biopsy NSCLC
      specimens, 22 (21.0%) stained NOB1 - , 35 (33.3%) stained +, 31 (29.5%) stained
      ++ and 17 (16.2%) stained +++. The early response rate to chemotherapy was 59.0%
      in overall NSCLC. Early response to chemotherapy has no relationship with
      patients' age, gender, smoke status, performance status and chemotherapy regimens
      (P>0.05), but related with TMN stage, histopathological grade, as well as NOB1
      expression (P < 0.05). In squamous cell carcinoma and non-squamous cell
      carcinoma, same results were found. Logistic regression analysis showed TMN
      stage, histopathological grade and NOB1 expression were independent prognosis
      factors for early response to cisplatin-based chemotherapy in patients with
      advanced NSCLC. After adjusted by TMN stage and histopathological grade, the OR
      for NOB1 expression was 1.429 (95% CI 1.115-1.743, P = 0.008) for early response
      to chemotherapy. CONCLUSION: Our results suggest that enhanced expression of NOB1
      related with poor early response to cisplatin-based chemotherapy in patients with
      advanced non-small cell lung cancer.

PMID- 25971310
TI  - Effects of low-flow sevoflurane anesthesia on renal function in low birth weight
      infants.
AB  - BACKGROUND: Low-flow sevoflurane anesthesia has been shown to influence renal
      function in rats, but not in adult humans. Presently, no study has assessed the
      effects of sevoflurane on renal function in low birth weight infants. Our aim was
      to study the renal function in low birth weight infants undergoing surgery with
      low-flow sevoflurane anesthesia. METHODS: Forty infants graded as American
      Society of Anesthesiologists (ASA) grade I or II undergoing abdominal surgery
      were selected. After the induction of anesthesia, they received sevoflurane semi
      closed inhalation anesthesia with an oxygen flow rate of 1 L/minute. According to
      patient vital signs, in-tidal sevoflurane concentration was maintained at 2.5%
      4.0%. Peripheral vein blood samples and urine specimens were obtained before
      surgery (T0), at the end of surgery (T1), and 24 (T2), 48 (T3), and 72 hours (T4)
      after surgery. Serum creatinine (Cr), blood urea nitrogen (BUN), urinary retinol
      binding protein (RBP), and beta-N-acetyl-glucosaminidase (NAG) levels were
      determined at these time points. Also, a temperature probe was inserted into the
      center of a soda lime canister and temperature readings were obtained. RESULTS:
      There were no significant differences in Cr and BUN before and after surgery (P >
      0.05). However, RBP and NAG levels increased after surgery (P < 0.05), but
      returned to preoperative levels 72 hours (T4) after surgery. The highest soda
      lime temperature was 37.3 +/- 3.1 degrees C. CONCLUSIONS: Low-flow sevoflurane
      semi-closed inhalation anesthesia has no significant effect on the renal function
      of low birth weight infants.

PMID- 25971311
TI  - F508del-cystic fibrosis transmembrane regulator correctors for treatment of
      cystic fibrosis: a patent review.
AB  - INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disease
      caused by malfunction of CF transmembrane regulator (CFTR). The deletion of a
      phenylalanine at residue 508 (F508del) is the most common mutation that causes
      cellular processing, chloride channel gating and protein stability defects in
      CFTR. Pharmacological modulators of F508del-CFTR, aimed at correcting the
      cellular processing defect (correctors) and the gating defect (potentiators) in
      CFTR protein, are regarded as promising therapeutic agents for CF disease.
      Endeavors in searching F508del-CFTR modulators have shown encouraging results,
      with several small-molecule compounds having entered clinical trials or even
      represented clinical options. AREAS COVERED: This review covers the discovery of
      F508del-CFTR correctors described in both patents (2005 - present) and scientific
      literatures. EXPERT OPINION: Cyclopropane carboxamide derivatives of CFTR
      correctors continue to dominate in this area, among which lumacaftor (a NBD1
      MSD1/2 interface stabilizer) is the most promising compound and is now under the
      priority review by US FDA. However, the abrogation effect of ivacaftor
      (potentiator) on lumacaftor suggests the requirement of discovering new
      correctors and potentiators that can cooperate well. Integration screening for
      simultaneously identifying combinations of correctors (particularly NBD1
      stabilizer) and potentiators should provide an alternative strategy. A recently
      reported natural product fraction library may be useful for the integration
      screening.

PMID- 25971312
TI  - Research on PTSD prevalence in OEF/OIF Veterans: expanding investigation of
      demographic variables.
AB  - BACKGROUND: A series of recent articles has reported on well-designed studies
      examining base rates of posttraumatic stress disorder (PTSD) screenings within
      the Operation Enduring Freedom (Afghanistan conflict)/Operation Iraqi Freedom
      (Iraq conflict) (OEF/OIF) military population. Although these studies have a
      number of strengths, this line of research points out several key areas in need
      of further examination. OBJECTIVE: Many OEF/OIF Veterans do not use available
      Veterans Affairs (VA) services, especially mental health care. This highlights
      the need to understand the differences between those who use and do not use the
      VA, especially as research with pre-OEF/OIF Veterans suggests that these two
      groups differ in significant ways. The high rates of PTSD-related concerns in non
      VA users also points to a need to understand whether-and where-Veterans are
      seeking care outside the VA and the accessibility of evidence-based, trauma
      focused treatments in the community and private sectors. Careful examination of
      relationship status is also paramount as little research has examined
      relationship status or other relationship context issues. Social support,
      especially from a spouse, can buffer the development of PTSD; however,
      relationship discord has the potential to greatly exacerbate PTSD symptomatology.
      Furthermore, given the additional risk factors for sexual minority Veterans to be
      exposed to trauma, the 2011 repeal of the US Military "Don't Ask, Don't Tell"
      policy, and the emergence of the VA as likely the largest health care provider
      for sexual minority Veterans, it will be critically important to study the trauma
      and mental health experiences of this group. CONCLUSIONS: Studies that examine
      prevalence rates of PTSD in the returning cohort contribute significantly to our
      understanding of the US OEF/OIF military population. Further study of PTSD in
      relation to demographic variables such as VA and non-VA use, relationship status,
      and sexual orientation will provide rich data that will enhance our ability to
      develop policy and practice to provide the best care to this population.

PMID- 25971313
TI  - Magnitude and kinetics of multifunctional CD4+ and CD8beta+ T cells in pigs
      infected with swine influenza A virus.
AB  - Although swine are natural hosts for influenza A viruses, the porcine T-cell
      response to swine influenza A virus (FLUAVsw) infection has been poorly
      characterized so far. We have studied Ki-67 expression and FLUAVsw-specific
      production of IFN-gamma, TNF-alpha and IL-2 in CD4(+) and CD8beta(+) T cells
      isolated from piglets that had been intratracheally infected with a H1N2 FLUAVsw
      isolate. IFN-gamma(+)TNF-alpha(+)IL-2(+) multifunctional CD4(+) T cells were
      present in the blood of all infected animals at one or two weeks after primary
      infection and their frequency increased in four out of six animals after
      homologous secondary infection. These cells produced higher amounts of IFN-gamma,
      TNF-alpha and IL-2 than did CD4(+) T cells that only produced a single cytokine.
      The vast majority of cytokine-producing CD4(+) T cells expressed CD8alpha, a
      marker associated with activation and memory formation in porcine CD4(+) T cells.
      Analysis of CD27 expression suggested that FLUAVsw-specific CD4(+) T cells
      included both central memory and effector memory populations. Three out of six
      animals showed a strong increase of Ki-67(+)perforin(+) CD8beta(+) T cells in
      blood one week post infection. Blood-derived FLUAVsw-specific CD8beta(+) T cells
      could be identified after an in vitro expansion phase and were multifunctional in
      terms of CD107a expression and co-production of IFN-gamma and TNF-alpha. These
      data show that multifunctional T cells are generated in response to FLUAVsw
      infection of pigs, supporting the idea that T cells contribute to the efficient
      control of infection. 

PMID- 25971314
TI  - Linear correlation between average fluorescence intensity of green fluorescent
      protein and the multiplicity of infection of recombinant adenovirus.
AB  - BACKGROUND: Adenoviral vector is an efficient tool for gene transfer. Protein
      expression is regulated by a number of factors, but the regulation by gene copy
      number remains to be investigated further. RESULTS: Assessed by flow cytometry,
      we demonstrated a significant linear correlation between average fluorescence
      intensity of green fluorescent protein (GFP) and a wide range of multiplicity of
      infection (MOI), spanning from 0.01 to 200. Average GFP intensity was calculated
      by mean fluorescence intensity (MFI) * percentage of infection (POI) (MFI * POI)
      and the correlation was observed in cells transduced with GFP-expressing
      adenoviral vector driven either by a cytomegalovirus (CMV) promoter for 3 to 6 h
      or by a human phosphoglycerate kinase (PGK) promoter for 18 to 24 h. Factors
      impacting this linear correlation include MOI of viral vector, strength of
      promoter driving GFP expression, cell type transduced and incubation time after
      gene transfer. We also found that weak GFP signals could be interfered by
      background signals, whereas strong GFP signals could overshot the detection
      limitation of the flow cytometer and resulted in a deviation from linearity which
      was prevented by adjusting the setting in flow cytometer. Moreover, we compared
      promoter strength as measured by MFI * POI and found that the relative activity
      of CMV promoter to PGK promoter was 20 to 47 folds in A549 cells and 32 to > 100
      folds in H1299 cells. CONCLUSIONS: The linear correlation between MFI * POI and a
      wide range of adenoviral MOI provides an efficient method to investigate factors
      regulating protein expression and to estimate virus titers.

PMID- 25971315
TI  - Assessing success--a commentary on the necessity of outcomes measures.
AB  - Measurements for outcomes reporting are not fully formed and utilized in the
      American addiction industry, though formulated and adopted elsewhere in the
      world. While studies have established demographic information about those needing
      and receiving treatment as well as the facilities that offer such treatment,
      short- and long-term outcomes are scantily reported. This commentary serves as a
      call to action to developing such metrics in the US by illustrating the benefits
      to treatment providers and clients of creating outcomes standards, and the
      subsequent improvements in quality of care needed to reach those standards.
      Benefits of developing these metrics beyond improved quality of care may also
      include a more efficient allocation of resources, such as time and money.
      Additionally, the delivery of more effective, personalized, and outcomes-driven
      addiction treatment may increase client buy-in and foster a more open
      communication channel between clients and providers during and after treatment. 

PMID- 25971316
TI  - Lymphoma of the orbit masquerading as Tolosa-Hunt syndrome.
AB  - BACKGROUND: Tolosa-Hunt syndrome is a rare clinical syndrome characterized by
      painful ophthalmoplegia and ipsilateral cranial neuropathies. It is caused by an
      inflammatory process of unknown etiology. CASE PRESENTATION: We present a case of
      a 77-year-old white man with history of Waldenstrom's macroglobulinemia
      transforming to large B-cell lymphoma who presented to a community physician
      complaining of 4 months of isolated right retro-orbital pain and later with
      diplopia, ptosis, 6th nerve and pupil-sparing partial 3rd nerve palsies as well
      as progressive neurological findings. His clinical course was complicated by
      debilitating neurological symptoms and multiple hospitalizations leading to a
      delay in diagnosis caused by incomplete initial workup. CONCLUSION: This case is
      a reminder that lymphoproliferative disorders often mimic other neurologic
      disorders and that Tolosa-Hunt is a rare diagnosis that must be considered a
      diagnosis of exclusion.

PMID- 25971317
TI  - The relationship between sperm viability and DNA fragmentation rates.
AB  - BACKGROUND: In humans, sperm DNA fragmentation rates have been correlated with
      sperm viability rates. Reduced sperm viability is associated with high sperm DNA
      fragmentation, while conversely high sperm viability is associated with low rates
      of sperm DNA fragmentation. Both elevated DNA fragmentation rates and poor
      viability are correlated with impaired male fertility, with a DNA fragmentation
      rate of >30% indicating subfertility. We postulated that in some men, the sperm
      viability assay could predict the sperm DNA fragmentation rates. This in turn
      could reduce the need for sperm DNA fragmentation assay testing, simplifying the
      infertility investigation and saving money for infertile couples. METHODS: All
      men having semen analyses with both viability and DNA fragmentation testing were
      identified via a prospectively collected database. Viability was measured by
      eosin-nigrosin assay. DNA fragmentation was measured using the sperm chromosome
      structure assay. The relationship between DNA fragmentation and viability was
      assessed using Pearson's correlation coefficient. RESULTS: From 2008-2013, 3049
      semen analyses had both viability and DNA fragmentation testing. A strong inverse
      relationship was seen between sperm viability and DNA fragmentation rates, with
      r=-0.83. If viability was <=50% (n=301) then DNA fragmentation was >= 30% for 95%
      of the samples. If viability was >=75% (n=1736), then the DNA fragmentation was
      <=30% for 95% of the patients. Sperm viability correlates strongly with DNA
      fragmentation rates. CONCLUSIONS: In men with high levels of sperm
      viability>=75%, or low levels of sperm viability<= 30%, DFI testing may be not be
      routinely necessary. Given that DNA fragmentation testing is substantially more
      expensive than vitality testing, this may represent a valuable cost-saving
      measure for couples undergoing a fertility evaluation.

PMID- 25971318
TI  - A Molecular and Serological Survey of Rickettsiales Bacteria in Wild Sika Deer
      (Cervus nippon nippon) in Shizuoka Prefecture, Japan: High Prevalence of
      Anaplasma Species.
AB  - We surveyed Rickettsiales bacteria, including Rickettsia, Ehrlichia, Anaplasma,
      and Neoehrlichia, in wild sika deer (Cervus nippon nippon) from Shizuoka
      prefecture, Japan. In spleen samples from 187 deer, Anaplasma phagocytophilum
      (deer type), A. bovis, and A. centrale were successfully detected by PCR assay
      targeting to 16S rDNA or p44/msp2, and their positive rates were 96.3% (180/187),
      53.5% (100/187), and 78.1% (146/187), respectively. Additionally, 2 or 3
      Anaplasma species could be detected from a single deer in 165 spleen samples
      (88.2%), indicating dual or triple infection. In contrast, A. phagocytophilum
      (human type) 16S rDNA, Rickettsia gltA, Ehrlichia p28/omp-1, and Neoehrlichia 16S
      rDNA could not be amplified. The serological test of 105 deer serum samples by
      immunofluorescence assay showed that the detection of antibodies against antigens
      of A. phagocytophilum HZ (US-human isolate) and Rickettsia japonica YH were 29.5%
      (31/105) and 75.2% (79/105), respectively. These findings suggest that A.
      phagocytophilum (deer type), A. centrale, and A. bovis are highly dominant and
      prevalent in wild sika deer from Shizuoka, a central region of Japan, and that
      the antibodies against some Rickettsiales bacteria have also been retained in
      deer blood. 

PMID- 25971319
TI  - Evaluation of Non-Viral Surrogate Markers as Predictive Indicators for Monitoring
      Progression of Human Immunodeficiency Virus Infection: An Eight-Year Analysis in
      a Regional Center.
AB  - Suitable methods for clinical monitoring of HIV-infected patients are crucial in
      resource-poor settings. Demographic data, clinical staging, and laboratory
      findings for 112 asymptomatic subjects positive for HIV were assessed at the
      first admission and the last visit from 2002 to 2010. Cox regression analysis
      showed hemoglobin (Hb) (HR = 0.643, P = 0.021) to be a predictive indicator for
      disease progression, while CD4, CD8, and platelet counts showed low HRs, despite
      having significant probability values. Hb and total lymphocyte count (TLC)
      rapidly declined from stage II to III (10.9 and 29.6%, respectively). Reduced CD4
      and platelet counts and Hb during stage I were associated with disease
      progression, and TLC was correlated with CD4 counts at the last follow-up (P <
      0.001). However, WHO TLC cutoff of 1,200 cell/mm(3) had 26.1% sensitivity and
      98.6% specificity. ROC curve analysis suggested that a TLC cutoff of 1,800
      cell/mm(3) was more reliable in this region. Statistical analysis and data mining
      findings showed that Hb and TLC, and their rapid decline from stage II to III, in
      addition to reduced platelet count, could be valuable markers for a surrogate
      algorithm for monitoring of HIV-infected subjects and starting anti-viral therapy
      in the absence of sophisticated detection assays. 

PMID- 25971320
TI  - Raltegravir and Abacavir/Lamivudine in Japanese Treatment-Naive and Treatment
      Experienced Patients with HIV Infection: a 48-Week Retrospective Pilot Analysis.
AB  - Abacavir/lamivudine (ABC/3TC) is a nucleoside reverse transcriptase inhibitor
      used for treating human immunodeficiency viral (HIV) infections. Hypersensitivity
      reactions such as skin eruptions caused by ABC are well-known, but rarely occur
      in Asians. Raltegravir (RAL) is an integrase strand transfer inhibitor, that is
      now increasingly, used for treating HIV infections because it has few adverse
      effects. This retrospective analysis assessed the efficacy and safety of combined
      ABC/3TC and RAL in both treatment-naive and -experienced Japanese patients with
      HIV infections. In all 11 treatment-naive patients (100%), virological
      suppression to undetectable level was achieved. Liver transaminases, renal
      function, and serum lipid profiles showed no exacerbations up to 48 weeks of
      treatment. In 12 patients who were switched from previous regimens to ABC/3TC and
      RAL, HIV viral load was undetectable in 11 patients (91.6%), but remained
      detectable in 1 patient with poor adherence. Major reasons for switching regimens
      to ABC/3TC and RAL were hyperlipidemia and nausea. After switching, these adverse
      effects improved, and no new adverse effects were observed. Despite the small
      number of participants in this study, the results support the combination of
      ABC/3TC and RAL as a possible treatment choice in Japanese individuals with HIV
      infection. 

PMID- 25971321
TI  - Verification of the Overestimation of the "Deaths Associated with Influenza
      Pandemic of 1918-1919, Japan" Claimed in a Demographic Study.
AB  - Official records show that the Japanese influenza death toll in 1918-1920 was 385
      thousand. However, a recently published study claims that the records are
      skeptical, claiming the figure to be "an anomaly by Asian standard," and re
      estimated the number to be about 2 million by its unique demographical
      calculation. However, it is not sound from the following socio-historical and
      statistical perspectives: i) Japan had developed accurate registration and
      surveillance systems which might not have existed in other developing countries;
      ii) there were unique socio-economic situations that claim that the relatively
      low mortality rate in Japan was not a "myth"; iii) the proposed re-estimation was
      an overestimation, because if it was a fact, about 1.6 million influenza deaths
      should have not been detected nationwide, i.e., about 3% of the population. Also,
      the influenza death toll was unrealistically large compared to the all-causes
      mortality of that period; iv) Japan started census in 1920 and it should have
      significantly affected the demographic data analysis. However, the effect by this
      artifact was not taken into account. Consequently, it caused the severe
      overestimation of the death; v) we recalculated the mortality using the same
      method and dataset but we could not reach an estimated figure similar to that
      claimed in the paper. 

PMID- 25971322
TI  - What We Have Learned from the Influenza A pH1N1 2009/10 Pandemic: High Clinical
      Impact of Human Metapneumovirus and Respiratory Syncytial Virus in Hospitalized
      Pediatric Patients.
AB  - The influenza pandemic in 2009/2010 shifted public awareness to respiratory tract
      infections caused by the influenza virus. A prospective study was conducted
      during the influenza pandemic from November 2009 through April 2010 to determine
      the causative pathogens and clinical symptoms present in all children and
      adolescents admitted to the University Children's Hospital, Duesseldorf, Germany,
      with signs and symptoms of respiratory tract infection. A total of 272 children
      and adolescents were admitted with symptoms of acute respiratory tract infection
      (ARI) or influenza-like illness. Viral pathogens were detected in 80% (218/272).
      However, influenza A pH1N1 infection was only detected in 11% (30/272) of
      children. Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) were
      the predominant identified pathogens that led to the admission of young
      tachypneic children with pneumonia in the post pandemic phase and the requirement
      for more intense treatment. During the pandemic and early post-pandemic phase the
      clinical impact of other respiratory viruses, such as HMPV and RSV, led to a
      higher clinical disease burden than pH1N1. Consequently, HMPV testing should be
      performed as routinely as RSV testing in patients hospitalized for ARI. Even
      while preparing for pandemics, the awareness of other respiratory viruses must be
      maintained.

PMID- 25971323
TI  - An Outbreak of Foodborne Illness Caused by Enteroaggregative Escherichia coli in
      a High School in South Korea.
AB  - In June 2013, a diarrheal outbreak occurred among high school students in
      Incheon, South Korea. We investigated the outbreak to identify the pathogen and
      mode of transmission. A case-control study using a self-administered
      questionnaire was conducted by local authorities and the Korean Centers for
      Disease Control and Prevention. Bacterial cultures of stool samples,
      environmental samples, and samples of preserved food items were prepared. PCR,
      serotyping, and pulsed-field gel electrophoresis (PFGE) were used to identify and
      characterize the outbreak-related pathogen. We identified 54 cases of
      gastroenteritis, with symptoms including diarrhea, abdominal pain, and nausea.
      None of the food items served in the high school cafeteria were significantly
      associated with illness, although the odds ratio for kippered trotters mixed with
      vegetables was relatively high (odds ratio: 2.92, 95% confidence interval: 0.62
      13.69). Enteroaggregative Escherichia coli (EAEC) was isolated from this item and
      the stool samples from 22 symptomatic students and 4 asymptomatic food handlers.
      The PFGE patterns of EAEC isolated from these sources were indistinguishable.
      This outbreak was caused by EAEC, and kippered trotters mixed with vegetables,
      perhaps contaminated by asymptomatic food handlers, were linked to the outbreak.
      This case-control study highlights the importance of safe food preparation. 

PMID- 25971324
TI  - Evaluation of the Efficacy of Novel Oxazolidinone Analogues against
      Nontuberculous Mycobacteria In Vitro.
AB  - Nontuberculous mycobacteria (NTM) are associated with a number of clinical
      diseases and only a few antitubercular agents are active against them.
      Oxazolidinones comprise a novel class of antimicrobials that inhibit bacterial
      protein synthesis at the ribosome. Linezolid, the first oxazolidinone
      antibacterial agent approved for clinical use, has excellent activity against
      some NTM but is ineffective against others. Sy142 and sy144 are novel
      oxazolidinones with demonstrated activties against Mycobacterium tuberculosis and
      Staphylococcus aureus. In this work, we compared the susceptibilities of key NTM
      species to linezolid, sy142, and sy144. The organisms included 21 isolates of
      Mycobacterium abscessus, 31 of Mycobacterium avium, 11 of Mycobacterium chelonae,
      24 of Mycobacterium fortuitum, 26 of Mycobacterium kansasii, and 17 of
      Mycobacterium intracellulare. For M. kansasii and M. fortuitum, linezolid showed
      excellent antimicrobial activity, and an equal MIC range was found in sy142 and
      sy144. For the species that linezolid was less active against, sy142 and sy144
      showed greater antimicrobial activities or exhibited equal compared to linezolid.
      Particularly, for M. avium and M. intracellulare, the in vitro antimicrobial
      activity of sy142 was 4-fold higher than that of linezolid. These results
      demonstrate the potential of these compounds to treat NTM infections. 

PMID- 25971325
TI  - The Economic Burden of Hepatitis A, B, and C in South Korea.
AB  - The prevalence of hepatitis in South Korea is relatively high compared to that in
      other high-income countries. For this reason, viral hepatitis infection not only
      affects the population's health, but also impacts national healthcare costs. This
      study was performed in order to estimate the individual economic costs of the
      hepatitis A, B, and C viruses as well as to determine, using nationally
      representative data, the trends in South Korea with respect to these viruses
      during the 2008-2011 period. The study found that the prevalence of hepatitis A
      had decreased, but those of hepatitis B and C had increased overall. The
      mortality rate of hepatitis C was higher than that of the other two types. The
      mortality rate of hepatitis B had changed little, whereas that of hepatitis C had
      risen. The total cost of hepatitis A had decreased, from US $62.2 million to US
      $45.7 million, although a notable exception occurred in 2009, when the cost was
      US $126.6 million. Conversely, the total cost of hepatitis B had increased
      rapidly during the same period, from US $501.4 million to US $607.8 million.
      Finally, the total cost of hepatitis C had also increased from US $63.9 million
      to US $90.7 million. The direct costs of hepatitis A, B, and C were estimated to
      account for approximately 35.5%, 46.6%, and 58.0% of the total, respectively.
      These findings demonstrate the economic burden associated with hepatitis A, B,
      and C, and demonstrate the need to establish an effective prevention and
      management policy for future planning in South Korea. 

PMID- 25971326
TI  - The First Report of Vibrio parahaemolyticus Strain O10:K60 in Japan, a New
      Combination of O and K Serotypes Isolated from a Patient with Gastroenteritis.
AB  - Vibrio parahaemolyticus is an important pathogen that causes gastroenteritis in
      humans, generally associated with the consumption of contaminated seafood,
      particularly raw shellfish. There are many serotypes in V. parahaemolyticus
      resulting from a combination of O and K antigens. Among them, O3:K6 and their
      variants, which represent the pandemic clone, are the most widespread strains
      worldwide. In this study, we examined V. parahaemolyticus isolated from a
      gastroenteritis patient's stool at a hospital in Saitama City, Japan in 2013.
      Serotyping of the O and K antigens identified the strain as O10:K60. To our
      knowledge, this is the first reported case of a V. parahaemolyticus strain with
      this antigen combination in Japan. Subsequently, we used PCR to assay for
      pathogenicity-associated genes, and found that it was positive for tdh, T3SS1,
      and T3SS2alpha genes. Antibiotic susceptibility tests showed that the strain was
      susceptible to all selected antibiotics except ampicillin. Moreover, we detected
      specific marker genes for the pandemic clone with two kinds of PCR assay. Our
      results suggest that the isolate O10:K60 is a newly emerging serotype that
      belongs to the pandemic clone. 

PMID- 25971327
TI  - Coronavirus Infections in Pediatric Outpatients with Febrile Respiratory Tract
      Infections in Hiroshima, Japan, over a 3-Year Period.
AB  - Previously, we conducted a 3-year prospective study to determine the viral causes
      of acute respiratory tract infections among 495 febrile pediatric outpatients. We
      collected 495 nasopharyngeal aspirate specimens, and used both real-time PCR
      assays and viral culture to test each for respiratory viruses other than
      coronavirus. Here, we used real-time PCR to test the 495 archival specimens for
      four human coronavirus strains. We identified 15 coronavirus-positive specimens:
      eight with OC43, 5 with NL63, 2 with HKU1, and none with 229E. Of the 15 children
      (5 boys) infected with human coronavirus, the mean age was 3.5 years, and the age
      range was 1.1 to 5.8 years; one child was diagnosed with lower respiratory
      infection; the other 14 were diagnosed with upper respiratory infection. Of these
      15 patients, none were hospitalized, 5 were infected with coronavirus alone, 8
      were co-infected with another virus, and 2 were co-infected with 2 other viruses.
      The multi-virus infections involved 6 adenoviruses, 3 respiratory syncytial
      viruses, 2 parainfluenza viruses, and 1 rhinovirus. In conclusion, the burden of
      human coronaviruses was relatively light among this cohort of 495 pediatric
      outpatients, and the incidence of these infections was low. 

PMID- 25971328
TI  - Diabetes mellitus is associated with breast cancer: systematic review, meta
      analysis, and in silico reproduction.
AB  - AIM: Breast cancer (BrCa) and diabetes mellitus (DM) are two major heath problems
      in women and the general population. This study explores the association between
      DM and breast cancer patients' survival outcomes, as well as the potential
      therapeutic merits of metformin. METHODS: To explore the association between DM
      and BrCa, we performed systematic literature search in EMBASE (www.embase.com)
      and MEDLINE (www.ncbi.nlm.nih.gov/pubmed) from January 1960 to April 2014 and
      systematically identified clinical studies that assessed the association between
      BrCa mortality and DM. The NCBI Gene Expression Omnibus (GEO) database was
      analyzed to identify micro-RNA change in BrCa cells treated by metformin, a
      common drug for DM worldwide. RESULTS: Twenty studies were selected for the meta
      analysis, of which 16 reported all-cause mortality and 12 reported cancer
      specific death. During our inclusion period, the cohorts encompassed a total of
      2,645,249 patients including more than 207,832 DM patients. Pre-existing DM was
      associated with a 37% increase of all-cause mortality risk for women with BrCa
      (HR=1.37; 95%CI: 1.34-1.41; P=0.02). DM was in general associated with a 17%
      increased risk for BrCa mortality in women (HR=1.17; 95%CI: 1.11-1.22; P<0.01).
      The GEO analysis revealed downregulation of a series of pro-tumorigenic micro
      RNAs following metformin treatment, which was in part restored by DICER
      knockdown. CONCLUSION: Women with DM are at higher risk of BrCa-specific and all
      cause mortality after initial breast cancer diagnosis. BrCa patients with DM
      could possibly benefit from metformin treatment via DICER mediation.

PMID- 25971329
TI  - Recurrence of retinal vein thrombosis with Pycnogenol(r) or Aspirin(r)
      supplementation: a registry study.
AB  - AIM: The aim of this study was to use Pycnogenol(r) to reduce the recurrence of
      retinal vein thrombosis (RVT) after a first episode. Pycnogenol(r) is an anti
      inflammatory, anti-edema and an antiplatelet agent with a "mild" antithrombotic
      activity. The registry, using Pycnogenol(r) was aimed at reducing the number of
      repeated episodes of RVT. METHODS: Possible management options--chosen by
      patients--were: standard management; standard management + oral Aspirin(r) 100 mg
      once/day (if there were no tolerability problems before admission); standard
      management + Pycnogenol(r) two 50 mg capsules per day (for a total of 100
      mg/day). Number of subjects, age, sex, distribution, percentage of smokers, and
      vision were comparable. RESULTS: Recurrent RVT was seen in 17.39% of controls and
      in 3.56% of subjects supplemented with Pycnogenol(r) (P<0.05 vs. controls). There
      was RVT in 15.38% of the subjects using Aspirin(r). The incidence of RVT was 4.88
      times higher with standard management in comparison with the supplement group and
      4.32 lower with Pycnogenol(r) supplementation in comparison with Aspirin(r).
      Vision level was better with Pycnogenol(r) (20/25 at nine months; P<0.05). With
      Pycnogenol(r), edema at the retinal level was also significantly reduced compared
      to the other groups. Pycnogenol(r) has a very good safety profile. In the
      Aspirin(r) group 26 completed 9 months and 6 subjects dropped out for
      tolerability problems. In the Aspirin(r) group, 2 minor, subclinical, retinal,
      hemorrhagic episodes during the follow-up were observed (2 subjects out of 26,
      equivalent to 7.69%). This pilot registry indicates that Pycnogenol(r) seems to
      reduce the recurrence of RVT without side effects. It does not induce new
      hemorrhagic episodes that may be theoretically linked to the use of Aspirin(r)
      (or other antiplatelets). CONCLUSION: Larger studies should be planned involving
      a wider range of conditions, diseases and risk factors associated to RVT and to
      its recurrence.

PMID- 25971330
TI  - Efficacy of amoxycillin and clarithromycin-based triple therapy for Helicobacter
      pylori eradication: a 10-year trend in Turin, Italy.

PMID- 25971331
TI  - A transition-metal-free Heck-type reaction between alkenes and alkyl iodides
      enabled by light in water.
AB  - A transition-metal-free coupling protocol between various alkenes and non
      activated alkyl iodides has been developed by using photoenergy in water for the
      first time. Under UV irradiation and basic aqueous conditions, various alkenes
      efficiently couple with a wide range of non-activated alkyl iodides. A tentative
      mechanism, which involves an atom transfer radical addition process, for the
      coupling is proposed. 

PMID- 25971332
TI  - The prognostic potential and oncogenic effects of PRR11 expression in hilar
      cholangiocarcinoma.
AB  - PRR11 is a newly identified oncogene in lung cancer, yet its role in others
      tumors remains unclear. Gastrointestinal tissue microarrays were used to evaluate
      PRR11 expression and its association with clinical outcome was analyzed in
      patients with hilar cholangiocarcinoma. Overexpression of PRR11 was observed in
      esophageal, gastric, pancreatic, colorectal, and hilar cholangiocarcinoma.
      Expression of PRR11 correlated with lymph node metastasis and CA199 level in two
      HC patient cohorts. After an R0 resection, a high level of PRR11 expression was
      found to be an independent indicator of recurrence (P = 0.001). In cell culture,
      PRR11 silencing resulted in decreased cellular proliferation, cell migration,
      tumor growth of QBC939 cells. Microarray analysis revealed that several genes
      involved in cell proliferation, cell adhesion, and cell migration were altered in
      PRR11-knockout cells, including: vimentin (VIM), Ubiquitin carboxyl-terminal
      hydrolase 1 (UCHL1), early growth response protein (EGR1), and System A amino
      acid transporter1 (SNAT1). Silencing PRR11 inhibited the expression of UCHL1,
      EGR1, and SNAT1 proteins, with immunoassays revealing a significant correlation
      among the levels of these four proteins. These results indicate that PRR11 is an
      independent prognostic indicator for patients with HC.

PMID- 25971333
TI  - C-Jun recruits the NSL complex to regulate its target gene expression by
      modulating H4K16 acetylation and promoting the release of the repressive NuRD
      complex.
AB  - The proto-oncogene c-Jun plays essential roles in various cellular processes,
      including cell proliferation, cell differentiation, and cellular apoptosis.
      Enormous efforts have been made to understand the mechanisms regulating c-Jun
      activation. The males absent on the first (MOF)-containing non-specific lethal
      (NSL) complex has been shown to positively regulate gene expression. However, the
      biological function of the NSL complex is largely unknown. Here we present
      evidence showing that c-Jun recruits the NSL complex to c-Jun target genes upon
      activation. The NSL complex catalyzes H4K16 acetylation at c-Jun target genes,
      thereby promoting c-Jun target gene transcription. More interestingly, we also
      found that the NSL complex promotes the release of the repressive NuRD complex
      from c-Jun target genes, thus activating c-Jun. Our findings not only reveal a
      new mechanism regulating c-Jun activation, but also identify the NSL complex as a
      c-Jun co-activator in c-Jun-regulated gene expression, expanding our knowledge of
      the function of the NSL complex in gene expression regulation. 

PMID- 25971335
TI  - A comprehensive study of cold protonated tyramine: UV photodissociation
      experiments and ab initio calculations.
AB  - We present a comprehensive experimental study of protonated tyramine ions in a
      cold 3D quadrupole ion trap coupled to a time-of-flight mass spectrometer.
      Multiple UV photodissociation techniques have been developed, including single
      and double resonance spectroscopy along with time-resolved excited state lifetime
      measurements through a picosecond pump-probe scheme. An original UV-UV hole
      burning method is presented which can be used without modification of the
      quadrupole ion trap. The electronic spectrum of the cold protonated tyramine
      exhibits well-defined vibronic transitions, allowing the firm assignment of its
      two low-lying energy conformations by comparison with CC2 ab initio excited state
      calculations. 

PMID- 25971334
TI  - Destabilisation of dimeric 14-3-3 proteins as a novel approach to anti-cancer
      therapeutics.
AB  - 14-3-3 proteins play a pivotal role in controlling cell proliferation and
      survival, two commonly dysregulated hallmarks of cancers. 14-3-3 protein
      expression is enhanced in many human cancers and correlates with more aggressive
      tumors and poor prognosis, suggesting a role for 14-3-3 proteins in tumorigenesis
      and/or progression. We showed previously that the dimeric state of 14-3-3
      proteins is regulated by the lipid sphingosine, a physiological inducer of
      apoptosis. As the functions of 14-3-3 proteins are dependent on their dimeric
      state, this sphingosine-mediated 14-3-3 regulation provides a possible means to
      target dimeric 14-3-3 for therapeutic effect. However, sphingosine mimics are
      needed that are not susceptible to sphingolipid metabolism. We show here the
      identification and optimization of sphingosine mimetics that render dimeric 14-3
      3 susceptible to phosphorylation at a site buried in the dimer interface and
      induce mitochondrial-mediated apoptosis. Two such compounds, RB-011 and RB-012,
      disrupt 14-3-3 dimers at low micromolar concentrations and induce rapid down
      regulation of Raf-MAPK and PI3K-Akt signaling in Jurkat cells. Importantly, both
      RB-011 and RB-012 induce apoptosis of human A549 lung cancer cells and RB-012,
      through disruption of MAPK signaling, reduces xenograft growth in mice. Thus,
      these compounds provide proof-of-principle for this novel 14-3-3-targeting
      approach for anti-cancer drug discovery. 

PMID- 25971336
TI  - Signal-off Electrochemiluminescence Biosensor Based on Phi29 DNA Polymerase
      Mediated Strand Displacement Amplification for MicroRNA Detection.
AB  - A target induced cycling strand displacement amplification (SDA) mediated by
      phi29 DNA polymerase (phi29) was first investigated and applied in a signal-off
      electrochemiluminescence (ECL) biosensor for microRNA (miRNA) detection. Herein,
      the target miRNA triggered the phi29-mediated SDA which could produce amounts of
      single-stranded DNA (assistant probe) with accurate and comprehensive nucleotide
      sequence. Then, the assistant probe hybridized with the capture probe and the
      ferrocene-labeled probe (Fc-probe) to form a ternary "Y" structure for ECL signal
      quenching by ferrocene. Therefore, the ECL intensity would decrease with
      increasing concentration of the target miRNA, and the sensitivity of biosensor
      would be promoted on account of the efficient signal amplification of the target
      induced cycling reaction. Besides, a self-enhanced Ru(II) ECL system was designed
      to obtain a stable and strong initial signal to further improve the sensitivity.
      The ECL assay for miRNA-21 detection is developed with excellent sensitivity of a
      concentration variation from 10 aM to 1.0 pM and limit of detection down to 3.3
      aM. 

PMID- 25971337
TI  - Robust enzyme-silica composites made from enzyme nanocapsules.
AB  - Novel enzyme composites are synthesized first by in situ polymerization around
      enzymes and a subsequent sol-gel process. Both the polymer shell and the silica
      shell with desired functional moieties provide not only great enzyme protection
      but also a favorable microenvironment, resulting in significantly enhanced
      activity and stability. 

PMID- 25971339
TI  - Effect of repeated harvesting on the content of caffeic acid and seven species of
      caffeoylquinic acids in sweet potato leaves.
AB  - The purpose of this study was to investigate the effect of repeated harvesting on
      the content of caffeic acid (CA) and seven species of caffeoylquinic acids (CQAs)
      in sweet potato leaves using a newly developed high-performance liquid
      chromatography method. Six cultivars and two breeding lines were used in this
      study. Leaves were collected at monthly intervals from 1st harvest (May) to 4th
      harvest (August) in 2011 and 2012. ANOVA analysis revealed that the contents of
      CQAs were significantly different among all cultivars and breeding lines, but no
      significant differences were found for CA. No annual variation was confirmed in
      CA and CQAs. Repeated harvest of sweet potato leaves affected the content of only
      4-CQA and 5-CQA. Post-hoc comparisons using Tukey's method indicated that the
      contents of 4-CQA and 5-CQA in sweet potato leaves harvested at first time were
      significantly higher compared to those at the other harvest times. 

PMID- 25971340
TI  - Do we need a vaccine against chikungunya?
AB  - During the last decade, the chikungunya (CHIKV) virus has expanded its range of
      activity, conquering new territories and becoming an important global health
      threat. In particular, the challenge represented by the recent emergence of CHIKV
      in the Americas has strengthened the need of a safe and effective vaccine.
      Although research on vaccines against CHIKV has been slow, a few vaccine
      candidates have been tested over the years. Inactivated and attenuated vaccine
      candidates have shown promising results in phase I/II trials, and engineered
      vaccines have proven to be safe and immunogenic in mouse and/or non-human primate
      models. Recently, a vaccine based on virus-like particles (VLP) has been
      successfully tested in a phase I trial. However, large phase I/II controlled
      trials, which are needed in order to provide evidence of vaccine efficacy, may be
      planned only under certain conditions. First, they should be conducted during
      epidemic periods, when a large number of cases occur, in order to ensure an
      adequate study power. Second, they are expensive and investments returns are not
      always guaranteed. To overcome this problem, public/private partnership and
      government support, the identification of target population groups for
      vaccination and the commitment of donor agencies are key factors for supporting
      both the development and the availability of vaccines against neglected tropical
      diseases like chikungunya.

PMID- 25971341
TI  - Hypoxia and Outcome Prediction in Early-Stage Coma (Project HOPE): an
      observational prospective cohort study.
AB  - BACKGROUND: The number of resuscitated cardiac arrest patients suffering from
      anoxic-ischemic encephalopathy is considerable. However, outcome prediction
      parameters such as somatosensory evoked potentials need revision because they are
      based on data predating the implementation of mild therapeutical hypothermia and
      because data from our own laboratory suggest that they may fail to predict
      prognosis accurately. The present research project "Hypoxia and Outcome
      Prediction in Early-Stage Coma" is an ongoing observational prospective cohort
      study that aims to improve outcome prediction in anoxic coma by limiting the
      effects of falsely pessimistic predictions at the intensive care unit. METHODS:
      Our outcome analysis is based on functional and behavioural definitions. This
      implies the analysis of the positive predictive value of prognostic markers
      yielding either positive or negative results. We also analyse the effect of
      covariates adjusted for age and sex such as sociodemographic variables,
      prognostic variables and treatment factors on functional and behavioural
      outcomes, with mixed effects regression models (i.e. fixed and random effects).
      We expect to enrol 172 patients based on the result of previous research. The
      null hypothesis is that there is a probability of <10 % that a positive outcome
      will be observed despite the presence of any of the predictors of a poor/negative
      outcome. We test the null hypothesis against a one-sided alternative using a
      Simon's two-stage design to determine whether it is warranted to recruit the full
      number of patients suggested by a power analysis. The second stage has a design
      with a Type I error rate of 0.05 and 80 % power if the true response rate is 25
      %. DISCUSSION: We aim to make a significant contribution to the revision and
      improvement of current outcome prediction methods in anoxic-ischemic
      encephalopathy patients. As a result, neurocritical care specialists worldwide
      will have considerably more accurate methods for prognosticating the outcome of
      anoxic-ischemic encephalopathy following cardiac arrest. This will facilitate the
      provision of treatment tailored to individual patients and the attainment of an
      optimal quality of life. It will also inform the decision to withdraw treatment
      with a level of accuracy never seen before in the field. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02231060 (registered 29 August 2014).

PMID- 25971342
TI  - Air radon concentration decrease in a waste water treatment plant.
AB  - (222)Rn is a naturally occurring gas created from the decay of (226)Ra. The long
      term health risk of breathing radon is lung cancer. One particular place where
      indoor radon concentrations can exceed national guidelines is in wastewater
      treatment plants (WWTPs) where treatment processes may contribute to ambient
      airborne concentrations. The aim of this paper was to study the radon
      concentration decrease after the application of corrective measures in a Spanish
      WWTP. According to first measures, air radon concentration exceeded International
      Commission Radiologica1 Protection (ICRP) normative (recommends intervention
      between 400 and 1000 Bq m(-3)). Therefore, the WWTP improved mechanical forced
      ventilation to lower occupational exposure. This measure allowed to increase the
      administrative controls, since the limitation of workers access to the plant
      changed from 2 h d(-1) (considering a maximum permissible dose of 20 mSv y(-1)
      averaged over 5 y) to 7 h d(-1). 

PMID- 25971343
TI  - A new two-phase media method for 226Ra activity measurement in water.
AB  - A new two-phase media method was developed for determination of (226)Ra activity
      in water. The method was calibrated by applying 7 standard (226)Ra waters with
      known activities. The method detects alphas in two media; 80 ml of water in a
      glass bottle with air or a non-polar liquid such as olive oil on top of the
      water. Alpha particles from (226)Ra, (222)Rn and progeny were detected by two
      polycarbonate track detectors (PCTDs) which were mounted on a holder inserted in
      the bottle so that one PCTD is placed in water and the other in air or in the non
      polar liquid. The bottles were hermetically sealed and kept for 40 or 48 d. The
      PCTDs in the bottles shaken every other day enhanced the sensitivity of the
      measurements. The Calibration Factors for the standard (226)Ra waters, air and
      olive oil above water are, respectively, (7.85 +/- 0.25) * 10(-3), (7.94 +/-
      0.13) * 10(-3) and 3.02 * 10(-2) tracks.cm(-2) kBq(-1) h(-1) m(3). 

PMID- 25971344
TI  - Studying the effect of radioactive wastes at the Ak-Tyuz deposit on radionuclide
      and elemental composition of water objects of Kichi-Kemin River.
AB  - This article reports on radionuclide and elemental composition studies of water
      and bottom sediment samples taken from Kichi-Kemin River in vicinity of the
      industrial area of the Ak-Tyuz thorium deposit in Kyrgyzstan near the border with
      Kazakhstan. The methods used included instrumental gamma-spectrometry, neutron
      activation analysis, X-ray fluorescent analysis and inductively coupled plasma
      mass spectrometry. The obtained results demonstrated the pronounced negative
      anthropogenic impact of this area on the quality of water in the Kichi-Kemin
      River imposing radiological hazards on this tributary of the trans-boundary Shu
      River. 

PMID- 25971345
TI  - Studying the effect of the Semipalatinsk Test Site on radionuclide and elemental
      composition of water objects in the Irtysh River.
AB  - The results of the field and laboratory studies of radiation and environmental
      state at the specific area of Irtysh River adjacent to the Semipalatinsk Test
      Site are provided. It was found that the radiation situation in this area is
      normal: equivalent dose of gamma-radiation = (0.11-0.13) uSv h(-1). Determination
      of radionuclide composition of soil, bottom sediment and water samples was
      performed by the methods of instrumental gamma-spectrometry, radiochemical
      analysis and the liquid scintillation beta-spectrometry. It was found that
      concentrations of the studied natural and artificial radionuclides in these
      objects are very low; no contamination with radionuclides was detected in this
      segment of Irtysh River. The article provides the results of elemental
      composition determination for samples of soil and bottom sediment (by X-ray
      fluorescence method) and water samples (by inductively coupled plasma mass
      spectrometry method). It is shown that the content of some elements (Li, Be, B,
      V, Cu, Sr, Mo) in the water of Irtysh River increases downstream. The additional
      studies are required to explain this peculiarity. 

PMID- 25971346
TI  - Natural radionuclides and toxic elements in transboundary rivers of Kazakhstan.
AB  - The paper reports on the study of radionuclide and elemental composition of
      water, bottom sediment and soil samples collected at the border areas of the
      following transboundary rivers in Kazakhstan: Chagan, Ural, Ilek, Tobol, Ayat,
      Irtysh, Emel, Ili, Tekes, Shu, Karabalta, Talas and Syrdarya. The employed
      analyses include the following methods: instrumental gamma-ray spectrometry,
      radiochemical analysis, neutron activation analysis, XRF and the inductively
      coupled plasma mass spectrometry (ICP-MS). Evidence of water environment
      contamination with radionuclides and toxic elements has been revealed in many of
      the studied rivers both in Kazakhstan and in adjacent countries. Transboundary
      transfer of the contaminants is most likely related to local industry (uranium
      mining and processing) and the presence of radioactive substances in the river
      basins. 

PMID- 25971347
TI  - Nanodosimetry of electrons: analysis by experiment and modelling.
AB  - Nanodosimetry experiments for high-energy electrons from a (131)I radioactive
      source interacting with gaseous nitrogen with sizes on a scale equivalent to the
      mass per area of a segment of DNA and nucleosome are described. The discrete
      ionisation cluster-size distributions were measured in experiments carried out
      with the Jet Counter. The experimental results were compared with those obtained
      by Monte Carlo modelling. The descriptors of radiation damages have been derived
      from the data obtained from ionisation cluster-size distributions. 

PMID- 25971348
TI  - Plant extractivism in light of game theory: a case study in northeastern Brazil.
AB  - BACKGROUND: Game theory enables the predictive study of the behavior of agents
      that recognize the mutual interdependence of their decisions and act rationally
      and strategically to maximize their own gains. In this paper, the extractivism of
      pequi (Caryocar coriaceum Wittm.) and fava d'anta (Dimorphandra gardneriana Tul.)
      in an area of common use of the semiarid region of northeastern Brazil is
      described as a model to illustrate a practical application of game theory in the
      interpretation of the phenomena analyzed in ethnobiological research. METHODS:
      Field research was conducted in the Araripe-Apodi National Forest. Semi
      structured interviews were conducted with 55 informants recognized as
      knowledgeable and experienced in the extractivism of pequi and fava d'anta in the
      region. In the interviews, information that could contribute to the
      identification and understanding of the focal points of extractivism in the
      region was surveyed. Data were analyzed under an analytical/descriptive approach
      using the "content analysis" technique. RESULTS: There was a logic of competitive
      entrepreneurship around the commercial extractivism of pequi and fava d'anta in
      the region. Among the extractivists of pequi, one of the main collection rules
      refers to the prohibition of removing immature fruits by using sticks or shaking
      the branches. In the extractivism of fava d'anta, no specific rules have been
      established by collectors, but there is a predominant behavior of withdrawing all
      available fruits (pods) on a tree in a single visit. In an analysis guided by
      game theory, the collection decisions adopted by extractivists to maximize gain
      from the activity can be considered justifiable from the standpoint of economic
      rationality. CONCLUSIONS: The "game of extractivism" of pequi and fava d'anta
      operates under conditions similar to the "tragedy of the commons." In this game,
      the non-cooperative solution is converted to the Nash equilibrium. The approach
      used in this study contributed to the identification of strategies and solutions
      to problems arising from the extractivism of pequi and fava d'anta.

PMID- 25971350
TI  - ERRgamma target genes are poor prognostic factors in Tamoxifen-treated breast
      cancer.
AB  - BACKGROUND: One-third of estrogen (ER+) and/or progesterone receptor-positive
      (PGR+) breast tumors treated with Tamoxifen (TAM) do not respond to initial
      treatment, and the remaining 70% are at risk to relapse in the future. Estrogen
      related receptor gamma (ESRRG, ERRgamma) is an orphan nuclear receptor with
      broad, structural similarities to classical ER that is widely implicated in the
      transcriptional regulation of energy homeostasis. We have previously demonstrated
      that ERRgamma induces resistance to TAM in ER+ breast cancer models, and that the
      receptor's transcriptional activity is modified by activation of the ERK/MAPK
      pathway. We hypothesize that hyper-activation or over-expression of ERRgamma
      induces a pro-survival transcriptional program that impairs the ability of TAM to
      inhibit the growth of ER+ breast cancer. The goal of the present study is to
      determine whether ERRgamma target genes are associated with reduced distant
      metastasis-free survival (DMFS) in ER+ breast cancer treated with TAM. METHODS:
      Raw gene expression data was obtained from 3 publicly available breast cancer
      clinical studies of women with ER+ breast cancer who received TAM as their sole
      endocrine therapy. ERRgamma target genes were selected from 2 studies that
      published validated chromatin immunoprecipitation (ChIP) analyses of ERRgamma
      promoter occupancy. Kaplan-Meier estimation was used to determine the association
      of ERRgamma target genes with DMFS, and selected genes were validated in ER+,
      MCF7 breast cancer cells that express exogenous ERRgamma. RESULTS: Thirty-seven
      validated receptor target genes were statistically significantly altered in women
      who experienced a DM within 5 years, and could classify several independent
      studies into poor vs. good DMFS. Two genes (EEF1A2 and PPIF) could similarly
      separate ER+, TAM-treated breast tumors by DMFS, and their protein levels were
      measured in an ER+ breast cancer cell line model with exogenous ERRgamma.
      Finally, expression of ERRgamma and these two target genes are elevated in models
      of ER+ breast cancer with hyperactivation of ERK/MAPK. CONCLUSIONS: ERRgamma
      signaling is associated with poor DMFS in ER+, TAM-treated breast cancer, and
      ESRRG, EEF1A2, and PPIF comprise a 3-gene signaling node that may contribute to
      TAM resistance in the context of an active ERK/MAPK pathway.

PMID- 25971352
TI  - Relationship of adiponectin to markers of oxidative stress in type 2 diabetic
      patients: influence of incipient diabetes-associated kidney disease.
AB  - PURPOSE: Adiponectin may be beneficial in incipient chronic kidney disease by
      antagonizing oxidative stress. We evaluated adiponectin, malondialdehyde (MDA),
      and superoxide dismutase (SOD), in type 2 diabetes mellitus patients (T2DP) with
      and without incipient nephropathy. METHODS: T2DP with glomerular filtration rate
      (GFR) >30 ml/min were compared with 20 healthy controls. Clinical and laboratory
      evaluations, levels of MDA (fluorimetric thiobarbituric test), SOD (cytochrome
      reduction method) and adiponectin (ELISA) were obtained. RESULTS: Sixty-four
      patients (GFR 91.44 +/- 38.50 ml/min, urinary albumin-to-creatinine ratio [UACR]
      20.81 [4.64-72.88 mg/g]) were included. MDA was higher in T2DP than in controls:
      3.97 (2.43-4.59) versus 1.35 (1.16-1.81) nmol/ml, p < 0.0001. MDA correlated with
      glycated hemoglobin (r = 0.40, p = 0.001), adiponectin (r = -0.28, p = 0.03),
      systolic blood pressure (r = -0.28, p = 0.03) and SOD (r = -0.35, p = 0.005);
      adiponectin (p = 0.01) and glycated hemoglobin (p = 0.02) remained significant
      predictors of MDA in multiple regression analysis. SOD was negatively correlated
      with glycemia (r = -0.71, p < 0.0001) and glycated hemoglobin (r = -0.5, p <
      0.0001). When patients were divided according to a ROC-derived adiponectin cutoff
      of 8.9 ug/ml, patients with higher adiponectin had lower MDA, [2.55 (2.35-3.60)
      vs. 4.10 (2.89-5.31) nmol/ml, p = 0.005] but similar SOD levels. In T2DP with
      nephropathy (GFR < 60 ml/min or UACR > 30 mg/g), the correlation of adiponectin
      with MDA was stronger, (r = -0.51, p = 0.004) confirmed in multiple regression
      analysis (p = 0.03). Adiponectin was not correlated with MDA, and SOD was
      inversely related to MDA in patients without nephropathy. CONCLUSION: Adiponectin
      is a significant predictor of MDA in early diabetic nephropathy, whereas SOD
      strongly depends only on glycemic control and is not directly related to
      adiponectin.

PMID- 25971349
TI  - Preliminary analysis of in utero low-level arsenic exposure and fetal growth
      using biometric measurements extracted from fetal ultrasound reports.
AB  - BACKGROUND: Early life exposure to arsenic is associated with decreased birth
      weight in highly exposed populations but little is known about effects of low
      level arsenic exposure on growth in utero. METHODS: Using a sample of 272
      pregnancies from New Hampshire we obtained biometric measurements directly from
      fetal ultrasound reports commonly found in electronic medical records. We used
      information extraction methods to develop and validate an automated approach for
      mining biometric measurements from the text of clinical reports. As a preliminary
      analysis, we examined associations between in utero low-level arsenic exposure
      (as measured by maternal urinary arsenic concentration) and fetal growth measures
      (converted to Z-scores based on reference populations for estimated fetal weight,
      head, and other body measures) at approximately 18 weeks of gestation. RESULTS:
      In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal
      urinary arsenic concentration (excluding arsenobetaine) was associated with a
      reduction in head circumference Z-score (Spearman correlation coefficient, rs = 
      0.08, p-value = 0.21) and a stronger association was observed among female
      fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value < 0.05).
      Although, associations were attenuated in adjusted analyses - among female
      fetuses a 1 MUg/L increase in maternal urinary arsenic concentration was
      associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference
      and 0.072 (95% CI: -0.151, 0.007) decrease in biparietal head diameter Z-score.
      CONCLUSIONS: Our study demonstrates that useful data can be extracted directly
      from electronic medical records for epidemiologic research. We also found
      evidence that exposure to low-level arsenic may be associated with reduced head
      circumference in a sex dependent manner that warrants further investigation.

PMID- 25971353
TI  - Plasma genistein and risk of prostate cancer in Chinese population.
AB  - OBJECTIVES: Genistein is one of the main soy isoflavones in our daily diet. There
      were studies proving that high-dietary intake of genistein may relate to the low
      morbidity and mortality of prostate cancer (PCa) in the Asian population. Since
      there were few studies of plasma genistein level in the Chinese population, we
      performed this study to preliminarily evaluate the associations among plasma
      genistein, epidemiologic factors and PCa in a Chinese population. METHODS:
      Between 2012 and 2013, 100 men over the age of 40 underwent prostate biopsy for
      PCa at Huashan Hospital, Shanghai, China. Clinical information, epidemiologic
      information and blood samples were collected prior to biopsy for each patient.
      All patients underwent 10-core ultrasound-guided transperineal prostate biopsy,
      and the pathology results were collected after biopsy. We measured the plasma
      genistein concentration of the blood samples and analyzed the results along with
      the clinical and epidemiologic information. RESULTS: Among the 100 patients, 46
      (46.0 %) were diagnosed with PCa. The median plasma genistein concentration of
      non-PCa patients (728.6 ng/ml) was significantly higher than that of PCa patients
      (513.0 ng/ml) (P < 0.05). In the univariate analysis, we found that age and
      smoking history were related to PCa (P < 0.05). In the multivariate analysis, we
      found that age, smoking history and plasma genistein were related to PCa (P <
      0.05). The age-adjusted odds ratio of PCa risk comparing plasma genistein level
      above median to that below median was 0.31 (95 % CI 0.13-0.71). CONCLUSION: Our
      study suggested that high concentration of plasma genistein level may contribute
      to the low incidence of prostate cancer in Chinese population.

PMID- 25971354
TI  - Corrigendum: Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting
      cardiac senescence.

PMID- 25971355
TI  - Continuing the Mission of Pediatric Poison Prevention through Prescriber
      Education.

PMID- 25971356
TI  - Rotation effect and anatomic landmark accuracy for midline placement of lumbar
      artificial disc under fluoroscopy.
AB  - PURPOSE: Total disc arthroplasty can be a viable alternative to fusion for
      degenerative disc disease of the lumbar spine. The correct placement of the
      prosthesis within 3 mm from midline is critical for optimal function. Intra
      operative radiographic error could lead to malposition of the prosthesis. The
      objective of this study was first to measure the effect of fluoroscopy angle on
      the placement of prosthesis under fluoroscopy. Secondly, determine the visual
      accuracy of the placement of artificial discs using different anatomical
      landmarks (pedicle, waist, endplate, spinous process) under fluoroscopy. METHODS:
      Artificial discs were implanted into three cadaver specimens at L2-3, L3-4, and
      L4-L5. Fluoroscopic images were obtained at 0 degrees , 2.5 degrees , 5 degrees ,
      7.5 degrees , 10 degrees , and 15 degrees  from the mid axis. Computerized
      tomography (CT) scans were obtained after the procedure. Distances were measured
      from each of the anatomic landmarks to the center of the implant on both
      fluoroscopy and CT. The difference between fluoroscopy and CT scans was compared
      to evaluate the position of prosthesis to each anatomic landmark at different
      angles. RESULTS: The differences between the fluoroscopy to CT measurements from
      the implant to pedicle was 1.31 mm, p < 0.01; implant to waist was 1.72 mm, p <
      0.01; implant to endplate was 1.99 mm, p < 0.01; implant to spinous process was
      3.14 mm, p < 0.01. When the fluoroscopy angle was greater than 7.5 degrees , the
      difference between fluoroscopy and CT measurements was greater than 3 mm for all
      landmarks. CONCLUSIONS: A fluoroscopy angle of 7.5 degrees  or more can lead to
      implant malposition greater than 3 mm. The pedicle is the most accurate of the
      anatomic landmarks studied for placement of total artificial discs in the lumbar
      spine.

PMID- 25971357
TI  - Relationship between lumbar spinal stenosis and psychosocial factors: a
      multicenter cross-sectional study (DISTO project).
AB  - INTRODUCTION: Lumbar spinal stenosis (LSS) is a lumbar spinal disorder that
      causes leg symptoms and intermittent claudication. It is reported that the risk
      factors for low back pain include age, family history, smoking, obesity, work
      related physical load, exercise, and depression. This was a multicenter, cross
      sectional survey, and the aim of this study was to investigate the prevalence of
      LSS by age and the relationships between LSS and psychosocial factors and job
      satisfaction. METHODS: This study enrolled subjects aged 50 years and over from a
      survey of LSS in 2177 hospitals and general practices nationwide. The clinical
      characteristics of the LSS and non-LSS groups were compared using the chi2 test,
      and the multivariate logistic regression analysis was performed to examine
      associations between exercise, perceived stress, strenuous use of the low back or
      legs, job satisfaction, and LSS. RESULTS: In total, 18,642 patients (8338 males,
      10,267 females) were analyzed. The rate of LSS was 38.3% and it increased with
      age. Regular exercise was less common among those in the LSS group than those in
      the non-LSS group (p<0.001). Satisfaction in all job-related items was less in
      the LSS group than in the non-LSS group (p<0.001). The odds for having LSS were
      higher in subjects having perceived stress and strenuous use of the low back or
      legs (p=0.001). The odds ratios of heart diseases and hypertension (p<0.001) were
      higher in the LSS group. CONCLUSION: This study investigated factors associated
      with LSS. The prevalence of LSS increased with age. Perceived stress and
      strenuous use of the low back or legs might be associated with LSS, and job
      satisfaction was lower with LSS.

PMID- 25971358
TI  - Where paths meet and cross: navigation by path integration in the desert ant and
      the honeybee.
AB  - Animals that travel large distances in search of food need to be equipped with
      navigation systems that are capable of keeping track of the distance and
      direction of travel throughout their outbound journey, so that they may return
      home expeditiously and without losing their way. The challenge of homing is
      especially acute when the environment is devoid of landmarks. Desert ants and
      honeybees are able to meet this challenge, despite their minuscule brains and
      restricted computational capacity. This article reviews some of the processes and
      mechanisms that underlie the homing abilities of these creatures, which are among
      the best-understood navigators in the animal kingdom. 

PMID- 25971359
TI  - Evaluation of US20150011555. An inhaled IP receptor agonist for the treatment of
      pulmonary arterial hypertension.
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease for which
      IP receptor agonists provide one of the main classes of treatment. Currently
      available agents tend to lack receptor selectivity. AREAS COVERED: Four salts of
      7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid,
      crystalline forms and compositions of each of these salts, and their use to treat
      conditions mediated by IP receptor activation, in particular PAH, are claimed.
      The claimed salts are particularly suited for delivery via inhalation and
      inhalation devices for their administration are claimed. EXPERT OPINION: This IP
      receptor agonist represents the first example of selecting a compound to treat
      PAH that was designed for delivery via inhalation. It indicates Novartis' desire
      to establish a broad portfolio of respiratory products.

PMID- 25971360
TI  - Radiotherapy combined with chemotherapy versus radiotherapy alone for early stage
      nasal natural killer/T-cell lymphoma: a meta-analysis.
AB  - OBJECTIVE: To compare the efficacy of radiotherapy (RT) plus chemotherapy (CMT)
      versus RT alone for early stage nasal natural killer (NK)/T-cell lymphoma.
      METHODS: All the eligible studies were searched by PubMed, Medline, Embase and
      the Cochrane Library. The meta-analysis was performed to compare odds ratios
      (ORs) for overall survival (OS), disease-free survival (DFS) and progression-free
      survival (PFS). RESULTS: Eight studies were included in the meta-analysis.
      Chemotherapy group did not significantly differ from RT group. The pooled OR and
      95% confidence interval (CI) for 1-year, 3-year, 5-year and 10-year OS was 1.25
      [0.84, 1.87], 1.10 [0.76, 1.58], 0.83 [0.59, 1.17] and 1.05 [0.70, 1.56]. In
      addition, the combined OR and 95% CI for 5-year DFS and PFS were 0.96 [0.53,
      1.73] and 0.71 [0.45, 1.12]. CONCLUSIONS: The current evidence suggests that CMT
      was not superior to RT alone. Radiotherapy may be still the main method in the
      treatment of early stage nasal NK/T-cell lymphoma.

PMID- 25971361
TI  - A transfer function approach for predicting rare cell capture microdevice
      performance.
AB  - Rare cells have the potential to improve our understanding of biological systems
      and the treatment of a variety of diseases; each of those applications requires a
      different balance of throughput, capture efficiency, and sample purity. Those
      challenges, coupled with the limited availability of patient samples and the
      costs of repeated design iterations, motivate the need for a robust set of
      engineering tools to optimize application-specific geometries. Here, we present a
      transfer function approach for predicting rare cell capture in microfluidic
      obstacle arrays. Existing computational fluid dynamics (CFD) tools are limited to
      simulating a subset of these arrays, owing to computational costs; a transfer
      function leverages the deterministic nature of cell transport in these arrays,
      extending limited CFD simulations into larger, more complicated geometries. We
      show that the transfer function approximation matches a full CFD simulation
      within 1.34 %, at a 74-fold reduction in computational cost. Taking advantage of
      these computational savings, we apply the transfer function simulations to
      simulate reversing array geometries that generate a "notch filter" effect,
      reducing the collision frequency of cells outside of a specified diameter range.
      We adapt the transfer function to study the effect of off-design boundary
      conditions (such as a clogged inlet in a microdevice) on overall performance.
      Finally, we have validated the transfer function's predictions for lateral
      displacement within the array using particle tracking and polystyrene beads in a
      microdevice. 

PMID- 25971363
TI  - PET/CT in primary mediastinal large B-cell lymphoma responding to rituximab-CHOP:
      An analysis of 106 patients regarding prognostic significance and implications
      for subsequent radiotherapy.

PMID- 25971362
TI  - Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor
      MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia.
AB  - High levels of microRNA-155 (miR-155) are associated with poor outcome in acute
      myeloid leukemia (AML). In AML, miR-155 is regulated by NF-kappaB, the activity
      of which is, in part, controlled by the NEDD8-dependent ubiquitin ligases. We
      demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being
      evaluated in clinical trials, decreases binding of NF-kappaB to the miR-155
      promoter and downregulates miR-155 in AML cells. This results in the upregulation
      of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a
      transcription factor important for myeloid differentiation, leading to monocytic
      differentiation and apoptosis. Consistent with these results, overexpression of
      miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces
      miR-155 expression and prolongs the survival of mice engrafted with leukemic
      cells. Our study demonstrates the potential of miR-155 as a novel therapeutic
      target in AML via pharmacologic interference with NF-kappaB-dependent regulatory
      mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a
      compound presently being evaluated in clinical trials in AML. As high miR-155
      levels have been consistently associated with aggressive clinical phenotypes, our
      work opens new avenues for microRNA-targeting therapeutic approaches to leukemia
      and cancer patients. 

PMID- 25971364
TI  - p53-dependent non-coding RNA networks in chronic lymphocytic leukemia.
AB  - Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a
      dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are
      used to identify patient subgroups with impaired p53 function, a comprehensive
      assessment of non-coding RNA targets of p53 in CLL is missing. We exploited the
      impaired transcriptional activity of mutant p53 to map out p53 targets in CLL by
      small RNA sequencing. We describe the landscape of p53-dependent microRNA/non
      coding RNA induced in response to DNA damage in CLL. Besides the key p53 target
      miR-34a, we identify a set of p53-dependent microRNAs (miRNAs; miR-182-5p, miR-7
      5p and miR-320c/d). In addition to miRNAs, the long non-coding RNAs (lncRNAs)
      nuclear enriched abundant transcript 1 (NEAT1) and long intergenic non-coding RNA
      p21 (lincRNA-p21) are induced in response to DNA damage in the presence of
      functional p53 but not in CLL with p53 mutation. Induction of NEAT1 and lincRNA
      p21 are closely correlated to the induction of cell death after DNA damage. We
      used isogenic lymphoma cell line models to prove p53 dependence of NEAT1 and
      lincRNA-p21. The current work describes the p53-dependent miRNome and identifies
      lncRNAs NEAT1 and lincRNA-p21 as novel elements of the p53-dependent DNA damage
      response machinery in CLL and lymphoma. 

PMID- 25971365
TI  - [Filling defect of the pulmonary artery?].

PMID- 25971366
TI  - [Ventilation as a trigger for organ dysfunction and sepsis].
AB  - Both in the intensive care setting and during surgery, mechanical ventilation
      plays an important role in the treatment of critically ill patients with lung
      injury, but also in lung healthy patients. Mechanical ventilation is noncurative
      and is accompanied by various severe side effects. It is hypothesized that
      multiorgan failure can be induced by mechanical ventilation. Furthermore, there
      is evidence to suggest cross-talk between lungs and other organs. In particular,
      the activation of specific cells and cell programs in peripheral organs is an
      important step on the way to multiorgan failure. In addition to bidirectional
      connection between the lung and brain, nonprotective ventilation leads to cell
      apoptosis in the kidney and intestine and leads to an increase of biomarkers for
      organ dysfunction. It is believed that both inflammation mediators and pro
      apoptotic factors are responsible for organ dysfunction. 

PMID- 25971367
TI  - [Burns and scalds in children].
AB  - BACKGROUND: Since pediatric emergencies and burn injuries are rare in prehospital
      emergency medicine, emergency teams can hardly develop routine in emergency care.
      OBJECTIVES: How to effectively treat burn injuries and avoid common errors?
      MATERIALS AND METHODS: A simple and severity-based therapy concept based on the
      current literature using the example of a case report is presented. RESULTS:
      About 80% of burns and scalds in children are not severe cases-in these patients
      an effective analgesia by intranasal administration is important and further
      invasive treatments are generally not necessary. The emergency care of children
      with severe burn injuries should start with intranasally administered analgesia
      and/or sedation. After an intravenous or intraosseous access is gained, moderate
      fluid therapy is started, which should be complemented by a fluid bolus only if
      signs of a shock are present. Additional administration of analgesia and/or
      sedation may be necessary. Estimation of the burned body surface area is best
      determined with the palm rule; the severity of the burn appears after a latency
      period. Induction of anesthesia and intubation are not required in the majority
      of cases. CONCLUSIONS: By applying a modified ABCDE scheme, all emergency teams
      can provide effective emergency care in children with burn injuries.

PMID- 25971369
TI  - Erratum to: Psychological distress, quality of life, symptoms and unmet needs of
      colorectal cancer survivors near the end of treatment.

PMID- 25971368
TI  - Differences in Symptom Reporting Between Males and Females at Baseline and After
      a Sports-Related Concussion: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Concussion literature and treatment guidelines are inconclusive
      regarding the role of sex in symptom reporting at baseline and post-concussion.
      Although empirical evidence is lacking, it is generally regarded that females
      have a more severe symptomatic presentation than males at all time-points on the
      concussion spectrum. OBJECTIVES: Our objective was to determine whether
      differences exist between males and females at baseline (pre-season/before
      concussion) or post-concussion for self-reported (1) prevalence of individual
      symptoms and (2) total symptom scores in high school and college athletes.
      DESIGN: Systematic review and meta-analysis of observational cohort studies;
      level of evidence, 1. METHODS: A computerized search of the PubMed, SPORTDiscus,
      CINAHL, and Scopus databases was performed. Meta-analysis Of Observational
      Studies in Epidemiology (MOOSE) guidelines were followed. Criteria for inclusion
      were (1) self-report of symptoms at any time within the concussion spectrum,
      including baseline and after concussion, (2) study sample included high school
      and/or collegiate athletes aged 12-26 years, (3) concussions occurred during
      participation in sport, and (4) symptom reporting was separated by sex. The
      Quality Assessment Tool for Cohort Studies, Q-Coh, was utilized for quality
      assessment. RESULTS: Twenty-one studies met the criteria for inclusion: seventeen
      had good quality and four, acceptable quality. At baseline, females had
      significantly higher odds than males of reporting the individual symptoms of
      vision/hearing problems, headache/migraine, difficulty concentrating,
      energy/sleep disturbances, and emotional disturbances. Post-concussion, only one
      symptom demonstrated significant differences between males and females, with
      females demonstrating lower odds of reporting confusion than males.
      Statistically, at baseline and post-concussion, females had significantly higher
      total symptom scores on the Post-Concussion Scale (PCS) and the Sport Concussion
      Assessment Tool 2 (SCAT2), but when the standard mean difference was interpreted
      after back-transformation, these results were clinically insignificant.
      CONCLUSIONS: The symptomatic presentation of males and females, most notably the
      prevalence of specific symptoms, is very divergent. Females had higher total
      symptom scores at baseline and post-concussion, however, clinically this cannot
      be interpreted as a meaningful difference. It is possible that these differences
      can be explained by normal hormonal changes associated with the menstrual cycle.
      The implications of these findings are that symptomatic presentation during an
      individual female's menstrual cycle needs to be taken into consideration post
      concussion when making return-to-play decisions, as returning to a completely
      asymptomatic level may not be a reasonable expectation.

PMID- 25971370
TI  - TGF-beta1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to
      rheumatic heart disease.
AB  - To investigate the involvement of transforming growth factor-beta1 (TGF-beta1)
      and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity
      of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial
      fibrillation (AF). The degree of myocardial fibrosis was evaluated using Masson
      staining. The expression levels of TGF-beta1, TIMP-4, matrix metalloproteinase-2
      (MMP-2), type I collagen, and type III collagen were estimated by Western blot
      analysis. Additionally, TGF-beta1 and TIMP-4 mRNA levels were quantified by qRT
      PCR. The effect of TGF-beta1 stimulation on TIMP-4 expression was assessed by in
      vitro stimulation of freshly isolated human atrial fibroblasts with recombinant
      human TGF-beta1, followed by Western blot analysis to detect changes in TIMP-4
      levels. Masson stain revealed that the left atrial diameter and collagen volume
      fraction were obviously increased in AF patients, compared to sinus rhythm (SR)
      controls (both P < 0.05). Western blot analysis showed significantly elevated
      levels of the AF markers MMP-2, type I collagen, and type III collagen in the AF
      group, in comparison to the SR controls (all P < 0.05). In the AF group, TGF
      beta1 expression was relatively higher, while TIMP-4 expression was apparently
      lower than the SR group (all P < 0.05). TIMP-4 expression level showed a negative
      association with TGF-beta1 expression level (r = -0.98, P < 0.01) and TGF-beta1
      stimulation of atrial fibroblasts led to a sharp decrease in TIMP-4 protein
      level. Increased TGF-beta1 expression and decreased TIMP-4 expression correlated
      with atrial fibrosis and ECM changes in the atria of RHD patients with AF.
      Notably, TGF-beta1 suppressed TIMP-4 expression, suggesting that selective TGF
      beta1 inhibitors may be useful therapeutic agents.

PMID- 25971371
TI  - Sfrp2 is a transcriptional target of SREBP-1 in mouse chondrogenic cells.
AB  - Secreted frizzled-related protein 2 (Sfrp2) is highly expressed in developing
      limbs and is associated with skeletal malformation such as Brachydactyly and
      Syndactyly. However, the mechanism by which Sfrp2 gene was transcriptionally
      regulated in chondrogenic cells is largely unknown. Here, we found that sterol
      regulatory element binding protein-1 (SREBP-1) regulated transcriptional
      activation of the Sfrp2 gene in chondrogenic cells. Overexpression of SREBP-1 led
      to stimulation of Sfrp2 promoter activity and increase of Sfrp2 mRNA in
      chondrogenic ATDC5 cells. Reporter gene assays using deleted Sfrp2 promoter
      constructs showed that the position between -1150 and -840 is required for SREBP
      1-mediated Sfrp2 promoter activity. Mutagenesis analysis showed that the SREBP-1
      binding site at nucleotide -935 to -926 is a functional motif for Sfrp2
      transcription. Promoter enzyme immunoassay and chromatin immunoprecipitation
      assay demonstrated that SREBP-1 binds directly to the SREBP-1-binding motif in
      the mouse Sfrp2 promoter. Thus, these results demonstrated that SREBP-1 acts as a
      positive regulator of Sfrp2 transcription in chondrogenic cells. 

PMID- 25971372
TI  - C-phycocyanin prevents cisplatin-induced mitochondrial dysfunction and oxidative
      stress.
AB  - The potential of C-phycocyanin (C-PC) to prevent cisplatin (CP)-induced kidney
      mitochondrial dysfunction was determined in CD-1 male mice. The CP-induced
      mitochondrial dysfunction was characterized by ultrastructural abnormalities and
      by decrease in the following parameters in isolated kidney mitochondria:
      adenosine diphosphate (ADP)-induced oxygen consumption (state 3), respiratory
      control ratio, ADP/oxygen (ADP/O) ratio, adenosine triphosphate synthesis,
      membrane potential, calcium retention, glutathione (GSH) content, and activity of
      respiratory complex I, aconitase, catalase, and GSH peroxidase. These
      mitochondria also showed increase in hydrogen peroxide production,
      malondialdehyde, and 3-nitrotyrosine protein adducts content. The above-described
      changes, as well as CP-induced nephrotoxicity, were attenuated in mice pretreated
      with a single injection of C-PC. Our data suggest that the attenuation of
      mitochondrial abnormalities is involved in the protective effect of C-PC against
      CP-induced nephrotoxicity. This is the first demonstration that C-PC pretreatment
      prevents CP-induced mitochondrial dysfunction in mice. 

PMID- 25971373
TI  - Mechanical stretch activates mammalian target of rapamycin and AMP-activated
      protein kinase pathways in skeletal muscle cells.
AB  - Cellular protein synthesis is believed to be antagonistically regulated by
      mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK)
      signaling pathways. In the present study, we examined the relationship between
      mTOR/p70 S6 kinase (p70S6K) and AMPK in response to mechanical stretch. C2C12
      myoblasts were grown on a silicone elastomer chamber to confluence and further
      cultured in differentiation medium for 4 days to form multinucleated myotubes.
      Cells were subjected to 15% cyclic uniaxial stretch for 4 h at a frequency of 1
      Hz. Phosphorylation of p70S6K at threonine 389 and AMPK at threonine 172 of the
      catalytic alpha subunit were concomitantly increased by mechanical stretch.
      Stimulation of the mTOR pathway by adding leucine and insulin increased the
      phosphorylation of p70S6K without inactivation of AMPK. In contrast, addition of
      compound C, a pharmacological inhibitor of AMPK, increased the phosphorylation of
      p70S6K in stretched cells. Activation of AMPK by the addition of 5-amino-4
      imidazolecarboxamide ribonucleoside reduced the phosphorylation of p70S6K in
      response to mechanical stretch. In conclusion, crosstalk between mTOR and AMPK
      signaling was not tightly regulated in response to physiological stimuli, such as
      mechanical stress and/or nutrients. However, pharmacological modulation of AMPK
      influenced the mTOR/p70S6K signaling pathway.

PMID- 25971374
TI  - Surgical management of acute cholecystitis.
AB  - BACKGROUND: Acute cholecystitis occurs in approximately 1% of patients with known
      gallstones. It presents as a surgical emergency and usually requires
      hospitalisation for treatment. It is associated with significant morbidity and
      mortality, particularly in the elderly. Cholecystectomy is advocated for acute
      cholecystitis; however, the timing of cholecystectomy and the value of the
      additional treatments have been a matter of debate. This review examines the
      available evidence regarding the optimal surgical management of patients with
      acute cholecystitis. METHODS: A literature search was performed on the MEDLINE,
      EMBASE and WHO International Clinical Trials Registry Platform, databases for
      English language publications. The MeSH headings 'cholecystitis', 'acute',
      'gallbladder', 'inflammation', 'surgery', 'cholecystectomy', 'laparoscopic',
      'robotic', 'telerobotic' and 'computer-assisted' were used. RESULTS: Data from
      eight randomised controlled trails and three population-based analyses show that
      early cholecystectomy for acute cholecystitis performed on the index admission is
      safe and not associated with increased conversion rates or morbidity in
      comparison to conservative treatment followed by elective cholecystectomy.
      Delaying cholecystectomy increases readmissions for gallstone-related events,
      complications, hospital stay and mortality in the elderly. Early cholecystectomy
      is also more cost-effective. Randomised trials addressing antibiotic use in acute
      cholecystitis suggest that antibiotics should be stopped on the day of
      cholecystectomy. Insufficient trials have been performed to address the optimal
      analgesia regime post cholecystectomy. Similarly, a lack of trials on
      intraoperative cholangiography and management of common bile duct stones in
      patients with acute cholecystitis means that treatment of concomitant bile duct
      stones should be based on institutional expertise and resource availability. As
      regards acute cholecystitis in elderly and high-risk patients, case series and
      retrospective studies would suggest that cholecystectomy is more effective and of
      lower mortality than percutaneous cholecystostomy. There is not enough evidence
      to support the routine use of robotic surgery, single-incision laparoscopic
      cholecystectomy or natural orifice transluminal endoscopic surgery (NOTES) in the
      treatment of acute cholecystitis. CONCLUSIONS: Trial evidence would favour a
      policy of early laparoscopic cholecystectomy following admission with acute
      cholecystitis. The optimal approach to support early cholecystectomy is suggested
      but requires evidence from further randomised trials.

PMID- 25971375
TI  - Influence of clay minerals on sorption and bioreduction of arsenic under anoxic
      conditions.
AB  - Adsorption of As(V) on various clay minerals including kaolinite (KGa-1),
      montmorillonite (SWy-1) and nontronites (NAU-1 and NAU-2), and subsequent
      bioreduction of sorbed As(V) to As(III) by bacterium Shewanella putrefaciens
      strain CN-32 were investigated. Nontronites showed relatively higher sorption
      capacity for As(V) primarily due to higher iron oxide content. Freundlich
      equation well described the sorption of As(V) on NAU-1, NAU-2 and SWy-1, while
      As(V) sorption isotherm with KGa-1 fitted well in the Langmuir model. The
      bacterium rapidly reduced 50% of dissolved As(V) to As(III) in 2 h, followed by
      its complete reduction (>ca. 98%) within 12 h. In contrast, sorption of As(V) to
      the mineral surfaces interferes with the activity of bacterium, resulting in low
      bioreduction of As(V) by 27% for 5 days of incubation. S. putrefaciens also
      promoted the reduction of Fe(III) present in the clay mineral to Fe(II). This
      study indicates that the sorption and subsequent bioreduction of As(V) on clay
      minerals can significantly influence the mobility of As(V) in subsurface
      environment.

PMID- 25971376
TI  - Routine recovery of organs for transplantation can be acceptable.

PMID- 25971377
TI  - Ventilator-associated pneumonia or bacterial colonization of the airway, what do
      probiotics decrease?

PMID- 25971378
TI  - Diffuse alveolar damage in nonresolving ARDS provides support for prolonged
      glucocorticoid treatment.

PMID- 25971379
TI  - An injured brain needs cooling down: yes.

PMID- 25971380
TI  - Balancing the "humors" in severe sepsis: still a role for extracorporeal
      therapies?

PMID- 25971381
TI  - Comments on Rees et al.: Safety and feasibility of a strategy of early central
      venous catheter insertion in a deployed UK military Ebola virus disease treatment
      unit.

PMID- 25971382
TI  - Mortality in children with respiratory failure transported using high-frequency
      oscillatory ventilation.

PMID- 25971383
TI  - Safety and feasibility of a strategy of early central venous catheter insertion
      in a deployed UK military Ebola virus disease treatment unit: response to
      comments by Bordes et al.

PMID- 25971384
TI  - To score or not to score during triage in the emergency department?

PMID- 25971385
TI  - The effect of hemodynamic monitoring depends entirely on the action to which it
      leads.

PMID- 25971386
TI  - The effect of hemodynamic monitoring depends entirely on the action that it leads
      to: response to comments by Cronhjort et al.

PMID- 25971387
TI  - Ten clinical indicators suggesting the need for ICU admission after Rapid
      Response Team review.

PMID- 25971388
TI  - Golden sputum.

PMID- 25971389
TI  - Thromboprophylaxis with low molecular weight heparin versus unfractionated
      heparin in intensive care patients: a systematic review with meta-analysis and
      trial sequential analysis.
AB  - PURPOSE: To compare benefits and harms of low molecular weight heparin (LMWH)
      versus unfractionated heparin (UFH) as thromboprophylaxis in intensive care unit
      (ICU) patients. METHODS: We conducted a systematic review with meta-analysis and
      trial sequential analysis (TSA) of randomised controlled trials (RCTs) comparing
      LMWH with UFH as thromboprophylaxis in adult ICU patients. We searched Ovid
      Medline, PubMed, Embase, Cochrane Library, UpToDate, Guidelines International
      Network, PROSPERO and the metaRegister of Controlled Trials through 3 December
      2014. Random effects risk ratios (RR) and 95% confidence intervals (CI) were
      derived for the endpoints deep vein thrombosis (DVT), pulmonary embolism (PE),
      major bleeding, mortality and net clinical benefit (any DVT, any PE, major
      bleeding and/or mortality). RESULTS: Eight RCTs (5567 patients) were included,
      whereof two were considered to have overall low risk of bias. Pooled analyses
      showed that LMWH compared with UFH reduced the risk of any DVT (RR 0.84, 95% CI
      0.71-0.98, p = 0.03) and resulted in a net clinical benefit (RR 0.90, 95% CI 0.83
      0.97, p = 0.01). There was no statistically significant difference in the risk of
      any PE (RR 0.65, 95% CI 0.41-1.03, p = 0.06), major bleeding (RR 0.99, 95% CI
      0.77-1.28, p = 0.96) or mortality (RR 0.93, 95% CI 0.78-1.12, p = 0.43). TSA
      supported the results of the conventional analysis on the outcome net clinical
      benefit but not on risk of any DVT. CONCLUSIONS: Evidence from this systematic
      review revealed a beneficial effect of LMWH compared with UFH when used as
      thromboprophylaxis in ICU patients.

PMID- 25971390
TI  - Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis:
      systematic review and meta-analysis.
AB  - PURPOSE: Plasma immunoglobulin concentrations are acutely altered in critically
      ill patients with sepsis. However, the association between immunoglobulin levels
      on the day of sepsis diagnosis and subsequent mortality is inconsistent. METHODS:
      Systematic review of studies that report immunoglobulin measurements and
      mortality among adults with sepsis managed in a critical care setting. Fixed and
      random effect meta-analyses were conducted using low IgG levels as primary
      exposure and acute mortality as the primary outcome. Both variables were used as
      defined in individual studies. RESULTS: The prevalence of a low immunoglobulin G
      (IgG) concentration on the day of sepsis diagnosis was variable [58.3% (IQR 38.4
      65.5%)]. Three cut-off points (6.1, 6.5 and 8.7 g/L) were used to define the
      lower limit of IgG concentrations in the included studies. A subnormal IgG level
      on the day of sepsis diagnosis was not associated with an increased risk of death
      in adult patients with severe sepsis and/or septic shock by both fixed and random
      effect meta-analysis (OR [95% CI] 1.32 [0.93-1.87] and 1.48 [0.78-2.81],
      respectively). CONCLUSIONS: This systematic review identifies studies of limited
      quality reporting heterogeneous sepsis cohorts with varying lower limits of
      normal for IgG. Although our data suggest that a subnormal IgG measurement on the
      day of sepsis diagnosis does not identify a subgroup of patients with a higher
      risk of death, further studies are needed to confirm or refute this finding, and
      whether optimal cut-offs and time windows can be defined for IgG measurement.
      This would determine whether patients receiving intravenous immunoglobulin
      therapy for sepsis could be stratified using IgG levels.

PMID- 25971391
TI  - Acute kidney injury after out-of-hospital cardiac arrest: risk factors and
      prognosis in a large cohort.
AB  - PURPOSE: Characteristics of acute kidney injury (AKI) occurring after out-of
      hospital cardiac arrest (OHCA) are incompletely described. We aimed to evaluate
      the prevalence of AKI, identifying risk factors and assessing the impact of AKI
      on outcome after OHCA. METHODS: Single-center study between 2007 and 2012 in a
      cardiac arrest center in Paris, France. All consecutive OHCA patients with at
      least one weight measurement and one serum creatinine level available and treated
      by therapeutic hypothermia were included, except those with chronic kidney
      disease and those dead on arrival. AKI was defined as stage 3 of the Acute Kidney
      Injury Network (AKIN) classification. Main outcome was day-30 mortality. Factors
      associated with AKI occurrence and day-30 mortality were evaluated by logistic
      regression. RESULTS: 580 patients (71.3% male, median age 59.3 years, initial
      shockable rhythm in 56.9% of cases) were included in the analysis. AKI stage 3
      occurred in 280 (48.3%) patients. Age, male gender, resuscitation duration, post
      resuscitation shock, public setting, and initial rhythm were associated with AKI
      stage 3. AKI stage 3 was associated with a significantly higher day-30 mortality
      rate [OR 1.60; 95% CI (1.05, 2.43); p = 0.03]. No independent association between
      AKI and neurologic outcome was observed. At day 30, 67 patients had a normal
      kidney function (eGFR >75 mL/min/1.73 m(2)), and five remained dialysis
      dependent. Patients with eGFR higher than 75 mL/min/1.73 m(2) at day 30 were
      younger and more frequently male. CONCLUSION: AKI stage 3 was frequent after OHCA
      and was associated with poorer outcome. Improvement strategies in post
      resuscitation care should consider AKI as a potential target of treatment.

PMID- 25971393
TI  - Understanding toxic shock syndrome.

PMID- 25971392
TI  - Impact of sedation and analgesia during noninvasive positive pressure ventilation
      on outcome: a marginal structural model causal analysis.
AB  - PURPOSE: There are limited data available about the role of sedation and
      analgesia during noninvasive positive pressure ventilation (NPPV). The objective
      of study was to estimate the effect of analgesic or sedative drugs on the failure
      of NPPV. METHODS: We studied patients who received at least 2 h of NPPV as first
      line therapy in a prospective observational study carried out in 322 intensive
      care units from 30 countries. A marginal structural model (MSM) was used to
      analyze the association between the use of analgesic or sedative drugs and NPPV
      failure (defined as need for invasive mechanical ventilation). RESULTS: 842
      patients were included in the analysis. Of these, 165 patients (19.6%) received
      analgesic or sedative drugs at some time during NPPV; 33 of them received both.
      In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95% confidence
      interval 0.6-5.4) or sedatives (odds ratio 2.8, 95% CI 0.85-9.4) alone was not
      associated with NPPV failure, but their combined use was associated with failure
      (odds ratio 5.7, 95% CI 1.8-18.4). CONCLUSIONS: Slightly less than 20% of
      patients received analgesic or sedative drugs during NPPV, with no apparent
      effect on outcome when used alone. However, the simultaneous use of analgesics
      and sedatives may be associated with failure of NPPV.

PMID- 25971394
TI  - The influence of mild hypothermia on reversal of rocuronium-induced deep
      neuromuscular block with sugammadex.
AB  - BACKGROUND: Mild hypothermia may be frequently induced due to cool environments
      in the operating room. The study analyzed patient recovery time and response to
      sugammadex after a prolonged rocuronium-induced deep neuromuscular block (NMB)
      during mild hypothermia. METHODS: Sixty patients were randomly (1:1) allocated to
      the mild hypothermia and normothermia groups, defined as having core temperatures
      between 34.5-35 degrees C and 36.5-37 degrees C, respectively. Patients received
      0.6 mg/kg of rocuronium, followed by 7-10 MUg/kg/min to maintain a deep NMB [post
      tetanic count (PTC) 1-2]. After surgery, the deep NMB was reversed with
      sugammadex 4.0 mg/kg. The primary end-point was the time until the train-of-four
      (TOF) ratio was 0.9. RESULTS: The appropriate neuromuscular function (TOF ratio
      >= 0.9) was restored after sugammadex was administered, even after hypothermia.
      The length of recovery in the hypothermia patients [mean (SD), 171.1 (62.1)
      seconds (s)] was significantly slower compared with the normothermia patients
      [124.9 (59.2) s] (p = 0.005). There were no adverse effects from sugammadex.
      CONCLUSIONS: Sugammadex safely and securely reversed deep rocuronium-induced NMB
      during mild hypothermia. An additional 46 s was required for recovery from a deep
      NMB in hypothermia patients. Based on the results, we think this prolonged
      recovery time is clinically acceptable. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01965067.

PMID- 25971395
TI  - Non-specific complaints in the ambulance; predisposing structural factors.
AB  - BACKGROUND: The pre-hospital assessment non-specific complaint (NSC) often
      applies to patients whose diagnosis does not match any other specific assessment
      correlating to particular symptoms or diseases, though some previous studies have
      found them to be related to serious underlying conditions. The aim was to
      identify whether the structural factors such as urgency according to the dispatch
      priority of the Emergency Medical Communication Centre (EMCC) or work load in the
      Emergency Medical Services (EMS) are predisposing factors for the assessment of
      NSC instead of a specific assessment. METHODS: All patients with assessed
      condition NSCs by the EMS to Sodersjukhuset during 2011 (n = 493) were compared
      with gender- and age-matched controls (n = 493), which were randomly drawn from
      all patients with specific conditions in the EMS, regarding day of week, time of
      day and priority set by EMCC with chi-squared tests and multivariate logistic
      regression models. RESULTS: Among patients with NSCs, more were females (58 %)
      and the median age was 82. Almost all patients were categorized with NSCs during
      the daytime (8 a.m. to 9 p.m.), i.e. 450 (91 %) as compared to 373 (75 %) of
      those with specific conditions (p < 0.01). The risk of having an EMS dispatched
      as low priority by the EMCC was almost doubled among patients with NSCs compared
      to controls (OR 1.97, 95 % CI 1.38-2.79). CONCLUSIONS: Since patients with NSCs
      appear most frequently during the hours with most transportations for the EMS,
      i.e. 10 a.m. to 2 p.m., and the risk of having the assessment NSC was doubled if
      the EMCC dispatched EMS as low priority, structural factors might be predisposing
      factors for the assessment.

PMID- 25971396
TI  - Kinematic relationship between rotation of lumbar spine and hip joints during
      golf swing in professional golfers.
AB  - BACKGROUND: Understanding the kinematics of the lumbar spine and hip joints
      during a golf swing is a basic step for identifying swing-specific factors
      associated with low back pain. The objective of this study was to examine the
      kinematic relationship between rotational movement of the lumbar spine and hip
      joints during a golf swing. METHODS: Fifteen professional golfers participated in
      this study with employment of six infrared cameras to record their golf swings.
      Anatomical reference system of the upper torso, pelvis and thigh segments, and
      the location of each hip and knee joint were defined by the protocols of the
      kinematic model of previous studies. Lumbar spine and hip joint rotational angle
      was calculated utilizing the Euler angle method. Cross-correlation and angle
      angle plot was used to examine the degree of kinematic relationship between
      joints. RESULTS: A fairly strong coupling relationship was shown between the
      lumbar spine and hip rotational movements with an average correlation of 0.81.
      Leading hip contribution to overall rotation was markedly high in the early stage
      of the downswing, while the lumbar spine contributed greater towards the end of
      the downswing; however, the relative contributions of the trailing hip and lumbar
      spine were nearly equal during the entire downswing. CONCLUSIONS: Most of the
      professional golfers participated in this study used a similar coordination
      strategy when moving their hips and lumbar spine during golf swings. The rotation
      of hips was observed to be more efficient in producing the overall rotation
      during the downswing when compared to the backswing. These results provide
      quantitative information to better understand the lumbar spine and hip joint
      kinematic characteristics of professional golfers. This study will have great
      potential to be used as a normal control data for the comparison with kinematic
      information among golfers with low back pain and for further investigation of
      golf swing-specific factors associated with injury.

PMID- 25971397
TI  - The activities of hospital nursing unit managers and quality of patient care in
      South African hospitals: a paradox?
AB  - BACKGROUND: Improving the quality of health care is central to the proposed
      health care reforms in South Africa. Nursing unit managers play a key role in
      coordinating patient care activities and in ensuring quality care in hospitals.
      OBJECTIVE: This paper examines whether the activities of nursing unit managers
      facilitate the provision of quality patient care in South African hospitals.
      METHODS: During 2011, a cross-sectional, descriptive study was conducted in nine
      randomly selected hospitals (six public, three private) in two South African
      provinces. In each hospital, one of each of the medical, surgical, paediatric,
      and maternity units was selected (n=36). Following informed consent, each unit
      manager was observed for a period of 2 hours on the survey day and the activities
      recorded on a minute-by-minute basis. The activities were entered into Microsoft
      Excel, coded into categories, and analysed according to the time spent on
      activities in each category. The observation data were complemented by semi
      structured interviews with the unit managers who were asked to recall their
      activities on the day preceding the interview. The interviews were analysed using
      thematic content analysis. RESULTS: The study found that nursing unit managers
      spent 25.8% of their time on direct patient care, 16% on hospital administration,
      14% on patient administration, 3.6% on education, 13.4% on support and
      communication, 3.9% on managing stock and equipment, 11.5% on staff management,
      and 11.8% on miscellaneous activities. There were also numerous interruptions and
      distractions. The semi-structured interviews revealed concordance between unit
      managers' recall of the time spent on patient care, but a marked inflation of
      their perceived time spent on hospital administration. CONCLUSION: The creation
      of an enabling practice environment, supportive executive management, and
      continuing professional development are needed to enable nursing managers to lead
      the provision of consistent and high-quality patient care.

PMID- 25971398
TI  - 'Practice what you preach': Nurses' perspectives on the Code of Ethics and
      Service Pledge in five South African hospitals.
AB  - BACKGROUND: A recent focus of the global discourse on the health workforce has
      been on its quality, including the existence of codes of ethics. In South Africa,
      the importance of ethics and value systems in nursing was emphasised in the 2011
      National Nursing Summit. OBJECTIVE: The study explored hospital nurses'
      perceptions of the International Code of Ethics for Nurses; their perceptions of
      the South African Nurses' Pledge of Service; and their views on contemporary
      ethical practice. METHODS: Following university ethics approval, the study was
      done at a convenience sample of five hospitals in two South African provinces. In
      each hospital, all day duty nurses in paediatric, maternity, adult medical, and
      adult surgical units were requested to complete a self-administered
      questionnaire. The questionnaire focused on their perceptions of the Code of
      Ethics and the Pledge, using a seven-point Likert scale. STATA((r)) 13 and NVIVO
      10 were used to analyse survey data and open-ended responses, respectively.
      RESULTS: The mean age of survey participants (n=69) was 39 years (SD=9.2), and
      the majority were female (96%). The majority agreed with a statement that they
      will promote the human rights of individuals (98%) and that they have a duty to
      meet the health and social needs of the public (96%). More nuanced responses were
      obtained for some questions, with 60% agreeing with a statement that too much
      emphasis is placed on patients' rights as opposed to nurses' rights and 32%
      agreeing with a statement that they would take part in strike action to improve
      nurses' salaries and working conditions. The dilemmas of nurses to uphold the
      Code of Ethics and the Pledge in face of workplace constraints or poor working
      conditions were revealed in nurses' responses to open-ended questions.
      CONCLUSION: Continuing education in ethics and addressing health system
      deficiencies will enhance nurses' professional development and their ethical
      decision-making and practice.

PMID- 25971399
TI  - The indirect costs of agency nurses in South Africa: a case study in two public
      sector hospitals.
AB  - BACKGROUND: Globally, flexible work arrangements - through the use of temporary
      nursing staff - are an important strategy for dealing with nursing shortages in
      hospitals. OBJECTIVE: The objective of the study was to determine the direct and
      indirect costs of agency nurses, as well as the advantages and the problems
      associated with agency nurse utilisation in two public sector hospitals in South
      Africa. METHODS: Following ethical approval, two South African public sector
      hospitals were selected purposively. Direct costs were determined through an
      analysis of hospital expenditure information for a 5-year period from 2005 until
      2010, obtained from the national transversal Basic Accounting System database. At
      each hospital, semi-structured interviews were conducted with the chief executive
      officer, executive nursing services manager, the maternity or critical care unit
      nursing manager, the human resource manager, and the finance manager. Indirect
      costs measured were the time spent on pre-employment checks, and nurse
      recruitment, orientation, and supervision. All expenditure is expressed in South
      African Rands (R: 1 USD=R7, 2010 prices). RESULTS: In the 2009/10 financial year,
      Hospital 1 spent R38.86 million (US$5.55 million) on nursing agencies, whereas
      Hospital 2 spent R10.40 million (US$1.49 million). The total estimated time spent
      per week on indirect cost activities at Hospital 1 was 51.5 hours, and 60 hours
      at Hospital 2. The estimated monetary value of this time at Hospital 1 was
      R962,267 (US$137,467) and at Hospital 2 the value was R300,121 (US$42,874), thus
      exceeding the weekly direct costs of nursing agencies. Agency nurses assisted the
      selected hospitals in dealing with problems of nurse recruitment, absenteeism,
      shortages, and skills gaps in specialised clinical areas. The problems
      experienced with agency nurses included their perceived lack of commitment,
      unreliability, and providing sub-optimal quality of patient care. CONCLUSION:
      Hospital managers and policy-makers need to address the effective utilisation of
      agency nurses and quality of patient care in tandem.

PMID- 25971400
TI  - The health system consequences of agency nursing and moonlighting in South
      Africa.
AB  - BACKGROUND: Worldwide, there is an increased reliance on casual staff in the
      health sector. Recent policy attention in South Africa has focused on the
      interrelated challenges of agency nursing and moonlighting in the health sector.
      OBJECTIVE: This paper examines the potential health system consequences of agency
      nursing and moonlighting among South African nurses. METHODS: During 2010, a
      cluster random sample of 80 hospitals was selected in four South African
      provinces. On the survey day, all nurses providing clinical care completed a self
      administered questionnaire after giving informed consent. The questionnaire
      obtained information on socio-demographics, involvement in agency nursing and
      moonlighting, and self-reported indicators of potential health system
      consequences of agency nursing and moonlighting. A weighted analysis was done
      using STATA((r)) 13. RESULTS: In the survey, 40.7% of nurses reported
      moonlighting or working for an agency in the preceding year. Of all participants,
      51.5% reported feeling too tired to work, 11.5% paid less attention to nursing
      work on duty, and 10.9% took sick leave when not actually sick in the preceding
      year. Among the moonlighters, 11.9% had taken vacation leave to do agency work or
      moonlighting, and 9.8% reported conflicting schedules between their primary and
      secondary jobs. In the bivariate analysis, moonlighting nurses were significantly
      more likely than non-moonlighters to take sick leave when not sick (p=0.011) and
      to pay less attention to nursing work on duty (p=0.035). However, in a multiple
      logistic regression analysis, the differences between moonlighters and non
      moonlighters did not remain statistically significant after adjusting for other
      socio-demographic variables. CONCLUSION: Although moonlighting did not emerge as
      a statistically significant predictor, the reported health system consequences
      are serious. A combination of strong nursing leadership, effective management,
      and consultation with and buy-in from front-line nurses is needed to counteract
      the potential negative health system consequences of agency nursing and
      moonlighting.

PMID- 25971401
TI  - Exploring the characteristics of nursing agencies in South Africa.
AB  - BACKGROUND: Nursing agencies are temporary employment service providers or labour
      brokers that supply nurses to health establishments. OBJECTIVE: This study was
      conducted to determine the characteristics of nursing agencies and their
      relationship with clients in the health sector. METHODS: During 2011, a cross
      sectional national survey of 106 nursing agencies was conducted. After obtaining
      informed consent, telephone interviews were conducted with a representative of
      the selected nursing agency using a pretested structured questionnaire. Questions
      focused on the following: ownership, date of establishment, province of
      operation, distribution of clients across private and public health facilities;
      existence of a code of conduct; nature of the contractual relationship between
      nursing agencies and their clients, and numbers and cadres of nurses contracted.
      The survey data were analysed using STATA((r)) 12. RESULTS: Fifty-two nursing
      agencies participated in the survey, representing a 49% response rate. The study
      found that 32 nursing agencies (62%) served private-sector clients only, which
      included private hospitals, homes for elderly people, patients in private homes,
      and private industry/company clinics, and only four (8%) of the agencies served
      the public sector only. Twenty-seven percent of nursing agencies provided
      services to homes for elderly individuals. Nursing agencies were more likely to
      have contracts with private-sector clients (84%) than with public-sector clients
      (16%) (p = 0.04). Although 98% of nursing agencies reported that they had a code
      of conduct, the proportion was higher for private-sector clients (73%) compared
      to public-sector clients (27%). In terms of quality checks and monitoring, 81% of
      agencies agreed with a statement that they checked the nursing council
      registration of nurses, 82% agreed with a statement that they requested certified
      copies of a nurse's qualifications. Only 21% indicated that they conducted
      reference checks of nurses with their past employers. CONCLUSIONS: Nursing
      agencies should enhance their quality assurance mechanisms when engaging
      contracted staff. Overall, the study findings suggest the need for improved
      governance and management of nursing agencies in South Africa.

PMID- 25971402
TI  - Social accountability and nursing education in South Africa.
AB  - BACKGROUND: There is global emphasis on transforming health workforce education
      in support of universal health coverage. OBJECTIVE: This paper uses a social
      accountability framework, specifically the World Health Organization's six
      building blocks for transformative education, to explore key informants'
      perspectives on nursing education in South Africa. METHODS: Using a snowballing
      sampling technique, 44 key informants were selected purposively on the basis of
      their expertise or knowledge of the research area. Semi-structured interviews
      were conducted with the key informants after informed consent had been obtained.
      The interviews were analysed using template analysis. RESULTS: South Africa has
      strategic plans on human resources for health and nursing education, training,
      and practice and has a well-established system of regulation and accreditation of
      nursing education through the South African Nursing Council (SANC). Key
      informants criticised the following: the lack of national staffing norms; sub
      optimal governance by both the SANC and the Department of Health; outdated
      curricula that are unresponsive to population and health system needs; lack of
      preparedness of nurse educators; and the unsuitability of the majority of nursing
      students. These problems are exacerbated by a perceived lack of prioritisation of
      nursing, resource constraints in both the nursing education institutions and the
      health training facilities, and general implementation inertia. CONCLUSION:
      Social accountability, which is an essential component of transformative
      education, necessitates that attention be paid to the issues of governance,
      responsive curricula, educator preparedness, and appropriate student recruitment
      and selection.

PMID- 25971403
TI  - Transforming nursing policy, practice and management in South Africa.

PMID- 25971405
TI  - Key components of external facilitation in an acute stroke quality improvement
      collaborative in the Veterans Health Administration.
AB  - BACKGROUND: Facilitation is a key component for successful implementation in
      several implementation frameworks; however, there is a paucity of research
      specifying this component. As part of a stroke quality improvement intervention
      in the Veterans Health Administration (VHA), facilitation plus data feedback was
      compared to data feedback alone in 11 VA medical facilities. The objective of
      this study was to elucidate upon the facilitation components of the stroke
      quality improvement. METHODS: We conducted a secondary evaluation of external
      facilitation using semi-structured interviews. Five facilitators and two program
      directors were interviewed. Qualitative analysis was performed on transcribed
      interviews to gain an understanding of the role and activities of external
      facilitators during the on-site and telephone facilitation. Quantitative
      frequencies were calculated from the self-reported time spent in facilitation
      tasks by facilitators. RESULTS: The external facilitators saw their role as
      empowering the clinical teams to take ownership of the process changes at the
      clinical sites to improve their performance quality. To fulfill this role, they
      reported engaging in a number of core tasks during telephone and on-site visits
      including: assessing the context in which the teams were currently operating,
      guiding the clinical teams through their planned changes and use of process
      improvement tools, identifying resources and making referrals, holding teams
      accountable for plan implementation with on-site visits, and providing support
      and encouragement to the teams. Time spent in facilitation activities changed
      across time from guiding change (early) to supporting efforts made by the
      clinical teams (later). Facilitation activity transitioned to more monitoring,
      problem solving, and intentional work to hand over the clinical improvement
      process to the site teams with the coach's role being increasingly that of a more
      distant consultant. Overall, this study demonstrated that external facilitation
      is not an event but rather a process where relationships and responsibilities
      evolve over time. CONCLUSIONS: This study shows that external facilitation
      involves core elements related to communication, relationship building, methods
      training, monitoring performance over time, and facilitating team-based problem
      solving. Importantly, this work demonstrates the fluid nature of external
      facilitation over time, as teams learn, grow, change, and experience changing
      contexts.

PMID- 25971406
TI  - Fifty-two-week long-term clinical study of luseogliflozin as monotherapy in
      Japanese patients with type 2 diabetes mellitus inadequately controlled with diet
      and exercise.
AB  - Luseogliflozin, a selective sodium glucose cotransporter 2 inhibitor, was
      demonstrated in a previous 24-week study of type 2 diabetic patients to be
      efficacious and well tolerated. This study mainly aimed to evaluate the long-term
      safety of luseogliflozin monotherapy in Japanese type 2 diabetic patients based
      on the Japanese guidelines. Additionally, long-term efficacy was also evaluated.
      Patients on diet and exercise therapy alone with an HbA1c of 6.9-10.5% received
      luseogliflozin 2.5 mg once daily for 52 weeks. For patients with insufficient
      glycemic control, this dose was able to be increased to 5 mg at Week 24. Adverse
      events (AEs), clinical laboratory tests, vital signs and 12-lead
      electrocardiograms were used to assess safety. Efficacy endpoints consisted of
      changes in HbA1c, fasting plasma glucose (FPG), and body weight from baseline. Of
      299 patients who received luseogliflozin, 279 completed the study. Most AEs were
      mild in severity with incidences of AEs and adverse drug reactions at 75.3% and
      16.7%, respectively. Although hypoglycemia was observed in 7 patients (2.3%), no
      major hypoglycemic episodes occurred. The incidences of AEs of special interest,
      including pollakiuria, volume depletion and urinary tract/genital infections,
      were at acceptable levels. Luseogliflozin significantly lowered HbA1c (-0.50%, P<
      0.001), FPG (-16.3 mg/dL, P< 0.001) and body weight (-2.68 kg, P< 0.001) at Week
      52 compared to baseline. Up-titration to 5 mg further improved glycemic control.
      In this long-term study of Japanese type 2 diabetic patients, luseogliflozin
      monotherapy was well tolerated for 52 weeks and provided a sustained glycemic
      lowering effect and reduced body weight. 

PMID- 25971408
TI  - Impact of Indoxyl Sulfate, a Uremic Toxin, on Non-Culprit Coronary Plaque
      Composition Assessed on Integrated Backscatter Intravascular Ultrasound.
AB  - BACKGROUND: Uremic toxin has emerged as an important determinant of
      cardiovascular risk. The aim of this study was to examine the relationship
      between serum uremic toxin and coronary plaque composition on integrated
      backscatter intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: IB-IVUS was
      performed in 47 patients with planned treatment for angina pectoris. Non-culprit
      intermediate plaque analyzed in this study had to be >5 mm apart from the
      intervention site. 3-D IB-IVUS analysis was performed to determine percent lipid
      volume (LV) and fibrous volume (FV). We also measured serum uremic toxins
      (indoxyl sulfate [IS], asymmetric dimethylarginine [ADMA], and p-cresol [PC]).
      Glomerular filtration rate correlated with IS (r=-0.329, P=0.04), but did not
      correlate with ADMA or PC. Percent LV correlated with IS (r=0.365, P=0.02), but
      did not correlate with ADMA or PC. Percent FV also correlated with IS (r=-0.356,
      P=0.03), but did not correlate with ADMA or PC. On multivariate regression, only
      IS was associated with percent LV (r=0.359, P=0.04) and percent FV (r=-0.305,
      P=0.04) independently of potentially confounding coronary risk factors.
      CONCLUSIONS: Among the uremic toxins, serum IS might be a novel useful biomarker
      to detect and monitor lipid-rich coronary plaque on IB imaging.

PMID- 25971409
TI  - Maturation-Based Model of Arrhythmogenic Right Ventricular Dysplasia Using
      Patient-Specific Induced Pluripotent Stem Cells.
AB  - Cellular reprogramming of somatic cells to patient-specific induced pluripotent
      stem cells (iPSCs) enables in-vitro modeling of human cardiac disorders for
      pathogenic and therapeutic investigations. However, using iPSC-derived
      cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains
      challenging because of the uncertainty regarding the ability of relatively
      immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic
      right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized
      by pathological fibrofatty infiltration and cardiomyocyte (CM) loss predominantly
      in the right ventricle (RV), leading to heart failure and lethal arrhythmias.
      Over 50% of affected individuals have desmosome gene mutations, most commonly
      inPKP2encoding plakophilin-2. Using Yamanaka's pluripotent factors, we generated
      iPSC lines from ARVD patients withPKP2mutations. We first developed a method to
      induce metabolic maturation of iPSC-CMs and showed that induction of adult-like
      metabolic energetics from an embryonic/glycolytic state is essential to model an
      adult-onset cardiac disease using patient-specific iPSCs. Furthermore, we showed
      that coactivation of normal peroxisome proliferator-activated receptor (PPAR)
      alpha and abnormal PPARgamma pathways in ARVD iPSC-CMs resulted in exaggerated CM
      lipogenesis, CM apoptosis, Na(+)channel downregulation and defective
      intracellular calcium handling, recapitulating the pathological signatures of
      ARVD. Using this model, we revealed novel pathogenic insights that metabolic
      derangement in an adult-like metabolic milieu underlies ARVD pathologies,
      enabling us to propose novel disease-modifying therapeutic strategies.

PMID- 25971407
TI  - State-building and human resources for health in fragile and conflict-affected
      states: exploring the linkages.
AB  - BACKGROUND: Human resources for health are self-evidently critical to running a
      health service and system. There is, however, a wider set of social issues which
      is more rarely considered. One area which is hinted at in literature,
      particularly on fragile and conflict-affected states, but rarely examined in
      detail, is the contribution which health staff may or do play in relation to the
      wider state-building processes. This article aims to explore that relationship,
      developing a conceptual framework to understand what linkages might exist and
      looking for empirical evidence in the literature to support, refute or adapt
      those linkages. METHODS: An open call for contributions to the article was
      launched through an online community. The group then developed a conceptual
      framework and explored a variety of literatures (political, economic, historical,
      public administration, conflict and health-related) to find theoretical and
      empirical evidence related to the linkages outlined in the framework. Three
      country case reports were also developed for Afghanistan, Burundi and Timor
      Leste, using secondary sources and the knowledge of the group. FINDINGS: We find
      that the empirical evidence for most of the linkages is not strong, which is not
      surprising, given the complexity of the relationships. Nevertheless, some of the
      posited relationships are plausible, especially between development of health
      cadres and a strengthened public administration, which in the long run underlies
      a number of state-building features. The reintegration of factional health staff
      post-conflict is also plausibly linked to reconciliation and peace-building. The
      role of medical staff as part of national elites may also be important.
      CONCLUSIONS: The concept of state-building itself is highly contested, with a
      rich vein of scepticism about the wisdom or feasibility of this as an external
      project. While recognizing the inherently political nature of these processes,
      systems and sub-systems, it remains the case that state-building does occur over
      time, driven by a combination of internal and external forces and that
      understanding the role played in it by the health system and health staff,
      particularly after conflicts and in fragile settings, is an area worth further
      investigation. This review and framework contribute to that debate.

PMID- 25971404
TI  - Special issue: transforming nursing in South Africa.

PMID- 25971411
TI  - Segregation in bimetallic nanoparticles.
AB  - Bimetallic nanoparticles are of interest due to their physical and chemical
      properties, which differ from their monometallic counterparts, and are dependent
      on size, composition and structure. Their unique chemical and physical properties
      make them useful in many optical, electronic and catalytic applications. In this
      perspective article we discuss segregation in bimetallic nanoparticles and
      highlight a recent analytical model based on minimization of energy.
      Computational approaches are discussed, along with a few examples and a
      comparison with the analytical approach. Experimental evidence for surface
      segregation is described, and finally, future directions are suggested. From this
      review of theoretical and experimental information it appears that a general
      consensus is starting to emerge that there are size-dependent variations in
      segregation in nanoparticles with the experimental data reasonably consistent
      with the theoretical models. 

PMID- 25971410
TI  - Tumorigenesis and peritoneal colonization from fallopian tube epithelium.
AB  - Ovarian cancer is the most lethal gynecological malignancy, primarily because its
      origin and initiation factors are unknown. A secretory murine oviductal
      epithelial (MOE) model was generated to address the hypothesis that the fallopian
      tube is an origin for high-grade serous cancer. MOE cells were stably altered to
      express mutation in p53, silence PTEN, activate AKT, and amplify KRAS alone and
      in combination, to define if this cell type gives rise to tumors and what genetic
      alterations are required to drive malignancy. Cell lines were characterized in
      vitro and allografted into mice. Silencing PTEN formed high-grade carcinoma with
      wide spread tumor explants including metastasis into the ovary. Addition of p53
      mutation to PTEN silencing did not enhance this phenotype, whereas addition of
      KRAS mutation reduced survival. Interestingly, PTEN silencing and KRAS mutation
      originating from ovarian surface epithelium generated endometrioid carcinoma,
      suggesting that different cellular origins with identical genetic manipulations
      can give rise to distinct cancer histotypes. Defining the roles of specific
      signaling modifications in tumorigenesis from the fallopian tube/oviduct is
      essential for early detection and development of targeted therapeutics. Further,
      syngeneic MOE allografts provide an ideal model for pre-clinical testing in an in
      vivo environment with an intact immune system. 

PMID- 25971412
TI  - Consenting for contact? Linking electronic health records to a research register
      within psychosis services, a mixed method study.
AB  - BACKGROUND: Research registers of potential participants linked to Electronic
      Health Records (EHRs) provide a basis for screening and identifying people
      suitable for studies. Such a system relies upon people joining the register and
      giving permission for their record to be used in this way. This study describes
      the process of training clinicians to explain EHR-linked research registers to
      service users, and to recruit them onto the register. METHOD: Training materials
      were developed for clinicians to help them describe the register to service
      users. These materials were based upon findings from focus groups reported
      elsewhere, they were then tested with 31 clinicians in early intervention
      psychosis services and each clinician discussed the register with service users
      on their caseload (n = 100 service users). Consultations were recorded and
      analysed in relation to their coverage of the training criteria. Service users
      also provided data on the acceptability of the process from their perspective.
      The content of clinicians' explanations to service users was described, and then
      compared against the likelihood of service users joining the register.
      Interpretive statistics (t-test and Chi-Squared) were used to explore differences
      between consultations in which service users agreed to join the register, and
      consultations where they did not agree to join. RESULTS: Service users appeared
      more likely to join the register if they felt control over what they signed up
      to, this necessitated understanding that they could decide when, how often, and
      by whom they were contacted, that joining the register did not automatically
      enlist them to future studies, and that they could change their mind in future.
      Clinicians' explanations did not always include that researchers would be able to
      see the service users' EHR. Service users often confused the idea of signing up
      to the register and signing up to studies themselves. Confidentiality was not
      well explained, but service users were not always concerned by confidentiality.
      CONCLUSION: EHR-linked research registers provide recruitment opportunities, and
      help service users to find out about research. Implementing these registers
      within mental health settings requires a trained clinical workforce and an
      informed service user population.

PMID- 25971414
TI  - Electrochemical Imaging of Dopamine Release from Three-Dimensional-Cultured PC12
      Cells Using Large-Scale Integration-Based Amperometric Sensors.
AB  - In the present study, we used a large-scale integration (LSI)-based amperometric
      sensor array system, designated Bio-LSI, to image dopamine release from three
      dimensional (3D)-cultured PC12 cells (PC12 spheroids). The Bio-LSI device
      consists of 400 sensor electrodes with a pitch of 250 MUm for rapid
      electrochemical imaging of large areas. PC12 spheroids were stimulated with K(+)
      to release dopamine. Poststimulation dopamine release from the PC12 spheroids was
      electrochemically imaged using the Bio-LSI device. Bio-LSI clearly showed the
      effects of the dopaminergic drugs l-3,4-dihydroxyphenylalanine (L-DOPA) and
      reserpine on K(+)-stimulated dopamine release from PC12 spheroids. Our results
      demonstrate that dopamine release from PC12 spheroids can be monitored using the
      device, suggesting that the Bio-LSI is a promising tool for use in evaluating 3D
      cultured dopaminergic cells and the effects of dopaminergic drugs. To the best of
      our knowledge, this report is the first to describe electrochemical imaging of
      dopamine release by PC12 spheroids using LSI-based amperometric sensors.

PMID- 25971415
TI  - The efficacy of vomer flap for closure of hard palate during primary lip repair.
AB  - BACKGROUND AND AIM: This study presents the institutional experience of the use
      of vomer flap for early closure of hard palate during unilateral complete cleft
      lip repair. The purpose of this study was to determine the survival rate of the
      vomer flap and to investigate its effect on the subsequent palatoplasty. PATIENTS
      AND METHODS: This retrospective analysis includes 101 non-syndromic patients with
      complete unilateral cleft lip who received a vomer flap for the closure of the
      hard palate during cleft-lip repair. Patients were aged 6 months to 28 years
      (median 1 year). Success rates of the vomer flaps were assessed clinically and
      through pre-operative photographs taken at the time of subsequent palate repair.
      Ninety-two patients returned for second-stage palate repair, and 74 patients with
      adequate post-operative follow-up information were statistically analysed.
      RESULTS: Of the 101 patients who were operated with primary lip repair and
      simultaneous vomer flap, only 54 (52.4%) vomer flaps healed completely. Out of 92
      patients who returned for subsequent palatoplasty, 71 (77.2%) were operated with
      the two-flap technique, and 19 (20.7%) received von Langenbeck repairs. Seven
      (9.1%) patients had a surgical complication. The failure of previous vomer repair
      and von Langenbeck surgical technique were identified as factors associated with
      post-operative complications. CONCLUSIONS: We conclude that failed vomer flaps
      increased the risks of complications in the subsequent palate repair.
      Furthermore, efforts to use von Langenbeck technique rather than the two-flap
      technique also resulted in increased surgical complications. As a result, we have
      abandoned the use of the vomer flap with primary lip repair.

PMID- 25971416
TI  - Near-infrared fluorescent angiography for demarcation of infected ulcer
      debridement.

PMID- 25971417
TI  - Reconstructive approach to hostile cranioplasty: A review of the University of
      Chicago experience.
AB  - BACKGROUND: Hostile sites for cranioplasty occur in patients with a history of
      radiation, infection, failed cranioplasty, CSF leak or acute infection. We review
      our series of autologous cranioplasties and present an approach to decision
      making for reconstructing these complex defects. METHODS: Patients with
      cranioplasty of a hostile cranial site at the University of Chicago between 2003
      and 2012 were identified. They were stratified into three groups: chimeric free
      flap with vascularized bone (the vascular group), non-vascularized bone with
      local coverage (the non-vascular group) and non-vascularized bone with free flap
      (the mixed group). The primary outcome measure was a major complication in the
      year following cranioplasty, identified by flap or bone graft failure. RESULTS:
      We reviewed 33 cases; 14 "vascular", 13 "non-vascular", and 8 "mixed". There was
      no difference in flap or bone graft failure rates, which were 7% (1/14) for the
      vascular group, 8% (1/13) for the non-vascular group, and 0% for the mixed group
      (p = NS). Overall complication rate was statistically different between the three
      groups (p = 0.01). The non-vascular group had the lowest complication rate (31%).
      Based on our data we developed an assessment score (The University of Chicago
      CRAnial Severity Score of Hostility, CRASSH) for patient and treatment
      stratification. CONCLUSIONS: Vascularized, non-vascularized and mixed
      reconstructive methods can be used successfully in these challenging situations.
      We offer the CRASSH to aid in aligning patients with the most appropriate
      autologous reconstruction method for their hostile cranial sites.

PMID- 25971418
TI  - A systematic review on external ear melanoma.
AB  - BACKGROUND: External ear melanoma accounts for only 1% of all cutaneous
      melanomas, and data on its optimal management and prognosis are limited. AIM: We
      aim to review the literature on external ear melanoma to guide surgeons in the
      treatment of this uncommon and peculiar pathology. MATERIALS AND METHODS: A
      systematic review of English language studies on ear melanoma published from 1993
      to 2013 was performed using the PubMed electronic database. Data on epidemiology,
      oncological treatment (tumor resection and regional lymph nodes management), and
      reconstruction were extrapolated from selected papers. RESULTS: The total number
      of patients was 858 (30 studies). The helix was the most common location (57%);
      superficial spreading melanoma was the most common histopathological subtype
      (41%). The mean Breslow thickness was 2.01 mm, with 88% of stage I-II patients.
      Sentinel lymph node biopsy was performed in 45% of patients, with 8% of positive
      nodes. Available data on its prognosis are fragmentary and contrasting, but the
      Breslow thickness appears to be the main prognostic factor. There is a tendency
      towards reduced resection margins and preservation of the underlying
      perichondrium and cartilage. Local flaps are the most popular reconstructive
      option. CONCLUSION: To the best of our knowledge, this systematic review presents
      the largest data series on external ear melanoma. There is no general agreement
      on its surgical management, but a favorable prognosis seems to justify the
      tendency towards conservative treatments.

PMID- 25971419
TI  - Dengue myocarditis and profound shock.

PMID- 25971420
TI  - Pain management in type I decompression sickness.

PMID- 25971421
TI  - In Hospital We Trust: Experiences of older peoples' decision to seek hospital
      care.
AB  - The purpose of this study was to explore how older people experience and perceive
      decisions to seek hospital care while receiving home health care. Twenty-two
      Swedish older persons were interviewed about their experiences of decision to
      seek hospital while receiving home health care. The interviews were analyzed
      using qualitative content analysis. The findings consist of one interpretative
      theme describing an overall confidence in hospital staff to deliver both medical
      and psychosocial health care, In Hospital We Trust, with three underlying
      categories: Superior Health Care, People's Worries, and Biomedical Needs.
      Findings indicate a need for establishing confidence and ensuring sufficient
      qualifications, both medical and psychological, in home health care staff to meet
      the needs of older people. Understanding older peoples' arguments for seeking
      hospital care may have implications for how home care staff address individuals'
      perceived needs. Fulfillment of perceived health needs may reduce avoidable
      hospitalizations and consequently improve quality of life. 

PMID- 25971422
TI  - New strategies for evaluating the quality of kidney grafts from elderly donors.
AB  - The increased demand for kidney transplantation and organ shortage resulted in
      the increased use of kidneys from suboptimal donors. Therefore, identification of
      kidneys that can be accepted without significantly compromising the outcome of
      allograft or recipient has become critical. A robust assessment of organ quality
      is of particular importance especially in kidneys from elderly donors in whom
      morphological and functional changes associated with aging and diseases are
      obvious. A number of predictive tools have been developed to help with evaluating
      the suitability of a deceased-donor kidney for transplantation. Among those,
      Kidney Donor Profile Index and zero hour graft biopsy in elderly donors have been
      already implemented in several transplant programs. This review captures the
      recent literature on this subject and discusses approaches for evaluating the
      quality of kidney grafts from elderly donors. 

PMID- 25971423
TI  - Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis.
AB  - The regulation of skeletal muscle lipolysis and fat oxidation is a complex
      process involving multiple proteins and enzymes. Emerging work indicates that
      skeletal muscle PLIN proteins likely play a role in the hydrolysis of
      triglycerides stored in lipid droplets and the passage of fatty acids to the
      mitochondria for oxidation. In adipocytes, PLIN1 regulates lipolysis by
      interacting with comparative gene identification-58 (CGI-58), an activator of
      adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is
      phosphorylated, releasing CGI-58 to activate ATGL and initiate triglyceride
      breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other
      PLIN family members undertake this role. The focus of this review is on the PLIN
      family proteins expressed in skeletal muscle: PLIN2, PLIN3, and PLIN5. To date,
      most studies involving these PLIN proteins have used nonmuscle tissues and cell
      cultures to determine their potential roles. Results from work in these models
      support a role for PLIN proteins in sequestering lipases during basal conditions
      and in potentially working together for lipase translocation and activity during
      lipolysis. In skeletal muscle, PLIN2 tends to mirror the lipid content and may
      play a role in lipid droplet growth and stability through lipase interactions on
      the lipid droplet surface, whereas the skeletal muscle roles of both PLIN3 and
      PLIN5 seem to be more complex because they are found not only on the lipid
      droplet, but also at the mitochondria. Clearly, further work is needed to fully
      understand the intricate mechanisms by which PLIN proteins contribute to skeletal
      muscle lipid metabolism. 

PMID- 25971424
TI  - The uselessness of procalcitonin in the diagnosis of focal bacterial central
      nervous system infection.
AB  - We investigated the utility of procalcitonin in early diagnosis of bacterial
      central nervous system (CNS) infection. Serum procalcitonin level was markedly
      elevated in the patients with systemic meningitis but not in the patients with
      brain abscess and subdural empyema. Procalcitonin may be useless to diagnose
      focal bacterial CNS infection. 

PMID- 25971425
TI  - Detection and characterization of atypical capripoxviruses among small ruminants
      in India.
AB  - Recent developments in molecular biology shed light on cross-species transmission
      of SPPV and GTPV. The present study was planned to characterize the
      capripoxviruses which were circulating in the field condition among sheep and
      goats using RPO30 gene-based viral lineage (SPPV/GTPV) differentiating PCR and
      sequencing of RPO30 and GPCR genes from clinical samples. Out of 58 scabs (35
      sheep and 23 goats) screened, 27 sheep and 18 goat scabs were found positive for
      capripox virus infections. With the exception of one sheep and one goat scabs,
      all the positive samples yielded amplicon size according to host origin, i.e.
      SPPV in sheep and GTPV in goats. In the above two exceptional cases, goat scab
      and sheep scab yielded amplicon size as that of SPPV and GTPV, respectively.
      Further, sequencing and phylogenetic analyses of complete ORFs of RPO30 and GPCR
      genes from six sheep and three goat scabs revealed that with the exception of
      above two samples, all had host-specific signatures and clustered according to
      their host origin. In case of cross-species infecting samples, sheep scab
      possessed GTPV-like signatures and goat scab possessed SPPV-like signatures. Our
      study identifies the circulation of cross-infecting SPPV and GTPV in the field
      and warrants the development of single-strain vaccine which can protect the
      animals from both sheeppox and goatpox diseases. 

PMID- 25971427
TI  - Management of ventricular arrhythmias in structural heart disease.
AB  - Ventricular arrhythmias (VA) are a source of significant morbidity and mortality
      in patients with structural heart disease (SHD). The advent of the implantable
      cardiac defibrillator (ICD) has had a positive effect on mortality, but the
      associated morbidity remains a significant problem. Modern treatment of VA has
      advanced far beyond medical therapy and includes strategies as simple as
      intelligent ICD programming and as complex as catheter ablation (CA). In these
      pages, the spectrum of management strategies will be discussed; from anti
      arrhythmic drugs and ICD implantation and programming to CA and autonomic
      modulation. The focus of this review will be on strategies for secondary
      prevention of VA in patients with SHD, supported by clinical evidence for their
      utilization. 

PMID- 25971426
TI  - Appearance of untreated bone metastases from breast cancer on FDG PET/CT:
      importance of histologic subtype.
AB  - PURPOSE: To determine if the histology of a breast malignancy influences the
      appearance of untreated osseous metastases on FDG PET/CT. METHODS: This
      retrospective study was performed under IRB waiver. Our Hospital Information
      System was screened for breast cancer patients who presented with osseous
      metastases, who underwent FDG PET/CT prior to systemic therapy or radiotherapy
      from 2009 to 2012. Patients with invasive ductal carcinoma (IDC), invasive
      lobular carcinoma (ILC), or mixed ductal/lobular (MDL) histology were included.
      Patients with a history of other malignancies were excluded. PET/CT was
      evaluated, blinded to histology, to classify osseous metastases on a per-patient
      basis as sclerotic, lytic, mixed lytic/sclerotic, or occult on CT, and to record
      SUVmax for osseous metastases on PET. RESULTS: Following screening, 95 patients
      who met the inclusion criteria (74 IDC, 13 ILC, and 8 MDL) were included. ILC
      osseous metastases were more commonly sclerotic and demonstrated lower SUVmax
      than IDC metastases. In all IDC and MDL patients with osseous metastases, at
      least one was FDG-avid. For ILC, all patients with lytic or mixed osseous
      metastases demonstrated at least one FDG-avid metastasis; however, in only three
      of seven patients were sclerotic osseous metastases apparent on FDG PET.
      CONCLUSION: The histologic subtype of breast cancer affects the appearance of
      untreated osseous metastases on FDG PET/CT. In particular, non-FDG-avid sclerotic
      osseous metastases were more common in patients with ILC than in patients with
      IDC. Breast cancer histology should be considered when interpreting non-FDG-avid
      sclerotic osseous lesions on PET/CT, which may be more suspicious for metastases
      (rather than benign lesions) in patients with ILC.

PMID- 25971428
TI  - Wild edible plant species utilized by a subsistence farming community in Obalanga
      sub-county, Amuria district, Uganda.
AB  - BACKGROUND: Farming communities have continuous interactions with their
      environment. Subsistence farmers are particularly vulnerable to the vagaries of
      weather. These are pre-requisites for increased wild edible plant consumption.
      This study mainly focused on indigenous knowledge regarding identity and use of
      wild edible plant species by the subsistence farmers of Obalanga. METHODS: A
      multistage sampling technique was used to identify Agonga parish. Systematic
      random sampling was used to locate 64 respondents stratified among children,
      adult females and males. After obtaining informed consent and assent, data was
      collected through semi-structured interviews using a checklist of open ended
      questions, focus group discussions and guided field visits. The free listing
      technique was employed to obtain data on plant identity and usage. RESULTS: Fifty
      one (51) species in forty three (43) genera spread in thirty two (32) families
      were identified. Age and gender had significant effects on respondents' wild
      edible plant species knowledge. The majority of edible wild plant species were
      herbs (47.1%) while grasses (3.9%) were the least. Fruits (51.0%) were the major
      parts consumed while tubers and roots constituted only 2.0% each. Eating uncooked
      as snacks (43.1%) was the favoured mode of consumption compared to roasting
      (2.0%). Preservation was mainly by solar drying. Wild edible plants traded within
      and without Obalanga community constituted only 15.7%. Almost all the edible
      plant species (94.1%) do not have any specific bye-laws for their conservation.
      Only Mangifera indica, Tamarindus indica and Vittaleria paradoxa representing
      5.9% of the species are protected by bye-laws. CONCLUSION: Disproportionate
      distribution of edible wild plant indigenous knowledge was noted in Obalanga with
      the lowest among the children. The marketed plant species in Obalanga can offer
      an opportunity for household livelihood diversification through value addition
      and trade under the umbrella of organic products. This will increase household
      incomes thereby contributing towards MDG 1 on eradicating extreme poverty and
      hunger. It is thus vital to document indigenous knowledge so that it is not lost
      as plant species disappear due to environmental degradation.

PMID- 25971430
TI  - Accuracy and cutoff values of delayed heart to mediastinum ratio with (123)I
      metaiodobenzylguanidine cardiac scintigraphy for Lewy body disease diagnoses.
AB  - BACKGROUND: Different studies have found diminished cardiac
      metaiodobenzylguanidine (MIBG) uptake in Lewy body (LB) related conditions
      (Parkinson's disease (PD) and Lewy body dementia (LBD)). However, delayed
      heart/mediastinum (d-H/M) ratio diagnostic cutoff points are debated in
      parkinsonian syndromes. METHODS: We performed a monocentric retrospective
      analysis on 62 consecutive parkinsonian patients who underwent an (123)I-MIBG
      scintigraphy, brain imaging and dopaminergic imaging using (123)I-Ioflupane
      single photon emission computed tomography (SPECT) from 2009 to 2013. The optimal
      d-H/M ratio was determined from a Receiver Operating Characteristic (ROC) curve
      and the sensitivity (Se), specificity (Sp) and likelihood ratios (LR) were
      calculated. 42 patients were diagnosed with LB diseases (20 PD, 22 LBD) and 20
      patients with other diseases. RESULTS: (123)I-MIBG scintigraphy helped to
      distinguish PD (p < 0.001) and LBD (p = 0.03) from other diseases. The optimal d
      H/M ratio was 1.48 (0.85 area under the ROC curve). Se and Sp were 83.3 %, and 85
      % respectively with positive and negative LR of 5.5 and 0.2 respectively.
      Patients with LBD had a lower d-H/M ratio than patients with PD (result not
      statistically significant) and a cutoff point at 1.2 could help to differentiate
      the two diseases. We did not find any correlation between the d-H/M ratio and
      clinical or (123)I-Ioflupane SPECT data. CONCLUSION: According to our population,
      the d-H/M ratio at 1.48 led to the best performance diagnosis with good Se, Sp
      and accuracy. In addition, a d-H/M ratio cutoff at 1.2 could help to
      differentiate PD from LBD.

PMID- 25971429
TI  - Combination of curcumin and bicalutamide enhanced the growth inhibition of
      androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2
      mediated targeting NF-kappaB/p65 and MUC1-C.
AB  - BACKGROUND: Prostate cancer is one of the most common malignancies in men. The
      mucin 1 (MUC1) heterodimeric oncoprotein is overexpressed in human prostate
      cancers with aggressive pathologic and clinical features, resulting in a poor
      outcome. However, the functional role for MUC1 C-terminal domain (MUC1-C) in
      androgen-independent prostate cancer occurrence and development has remained
      unclear. METHODS: Cell viability was measured by MTT assays. Western blot
      analysis was performed to measure the phosphorylation and protein expression of
      SAPK/JNK and ERK1/2, and MUC1-C, NF-kappaB subunit p65 and p50. Exogenous
      expression of MUC1-C, NF-kappaB subunit p65 was carried out by transient and
      electroporated transfection assays. RESULTS: We showed that curcumin inhibited
      the growth of androgen-independent prostate cancer cells and a synergy was
      observed in the presence of curcumin and bicalutamide, the androgen receptor
      antagonist. To further explore the potential mechanism underlining this, we found
      that curcumin increased the phosphorylation of ERK1/2 and SAPK/JNK, which was
      enhanced by bicalutamide. In addition, curcumin reduced the protein expression of
      MUC1-C and NF-kappaB subunit p65, which were abrogated in the presence of the
      inhibitors of MEK/ERK1/2 (PD98059) and SAPK/JNK (SP60015). A further reduction
      was observed in the combination of curcumin with bicalutamide. Moreover, while
      exogenous expression of MUC1-C had little effect on curcumin-reduced p65, the
      overexpression of p65 reversed the effect of curcumin on MUC1-C protein
      expression suggesting that p65 is upstream of MUC1-C. Intriguingly, we showed
      that exogenous expression of MUC1-C feedback diminished the effect of curcumin on
      phosphorylation of ERK1/2 and SAPK/JNK, and antagonized the effect of curcumin on
      cell growth. CONCLUSION: Our results show that curcumin inhibits the growth of
      androgen-independent prostate cancer cells through ERK1/2- and SAPK/JNK-mediated
      inhibition of p65, followed by reducing expression of MUC1-C protein. More
      importantly, there are synergistic effects of curcumin and bicalutamide. The
      negative feedback regulatory loop of MUC1-C to ERK1/2 and SAPK/JNK further
      demonstrates the role of MUC1-C that contributes to the overall responses of
      curcumin. This study unveils the potential molecular mechanism by which
      combination of curcumin with bicalutamide enhances the growth inhibition of
      androgen-independent prostate cancer cells.

PMID- 25971431
TI  - The Asian Grocery Store-Based Cancer Education Program: Creating New Education
      Modules.
AB  - Operating since 1994, the UCSD Moores Cancer Center's Asian Grocery Store-Based
      Cancer Education Program (the Program) is a proven and sustainable strategy for
      disseminating cancer and poison control information to Asian and Pacific Islander
      (API) communities. This paper describes the process taken to identify health
      topics that can be readily addressed within the Program's infrastructure and
      reports results of the pilot testing of the educational module that was developed
      by following that process. The development of each new module is guided by the
      Health Belief Model and the Tipping Point Model. The process starts with the
      selection of a health topic demonstrating pressing need and treatment options in
      the API community. Then, using the Pareto principle, reasonably modifiable risk
      factors are chosen to be addressed in the module. "Sticky messaging" for the
      modifiable risk factors is developed to package the health information as
      memorable and transmissible calls-to-action. Finally, grocery store outreaches
      were used to pilot test the new module to assess its effectiveness at
      facilitating health care information to API community members. By adhering to the
      steps described in this paper, the authors were able to: (1) select liver cancer
      as a pressing API health issue that could be positively impacted by the Program;
      (2) identify reasonably modifiable risk factors for the chosen health issue; (3)
      generate compelling call-to-action messages to decrease risk of exposure; and (4)
      demonstrate the cultural and linguistic alignment of the liver cancer control
      module. The development and testing of new health education modules follow a
      methodical process guided by scientific principles. Understanding and employing
      the elements of an existing evidence-based and sustainable health education
      program can increase the likelihood of success in addressing the health needs of
      the API community. 

PMID- 25971432
TI  - Lessons Learned from Implementing a Prostate Cancer Risk Assessment Program for
      Underserved High-Risk Men in the Community: the Prostate REACH Project.
AB  - Prostate cancer disproportionately affects Black men, who may also encounter
      barriers to participation in prostate cancer risk assessment. The Prostate Risk,
      Education and Assessment in the Community with Help (REACH) project was a
      community-based extension of a comprehensive prostate cancer risk assessment
      program at a comprehensive cancer center. The goals of the REACH project were the
      following: (1) establish a community prostate cancer risk assessment clinic, (2)
      conduct targeted recruitment, and (3) provide navigation services including
      follow-up for uninsured men. Key implementation steps included the following: (1)
      choosing a clinic site, (2) establishing patient access procedures, (3)
      establishing navigator services, (4) developing subsidy fund use guidelines, and
      (5) designing recruitment and promotion. Through community-based promotion, 64
      men inquired about the program and 26 (41 %) participated. Of those screened, 46
      % had abnormal results, and 2 men were diagnosed with prostate cancer. Here, we
      describe a unique demonstration project to implement a comprehensive prostate
      cancer risk assessment program in an underserved Black community and describe
      successes and challenges to inform future efforts to promote access to
      underserved men.

PMID- 25971434
TI  - A young man with skin rash and ascites.

PMID- 25971433
TI  - Non-monotonic dose-response relationships and endocrine disruptors: a qualitative
      method of assessment.
AB  - Experimental studies investigating the effects of endocrine disruptors frequently
      identify potential unconventional dose-response relationships called non
      monotonic dose-response (NMDR) relationships. Standardized approaches for
      investigating NMDR relationships in a risk assessment context are missing. The
      aim of this work was to develop criteria for assessing the strength of NMDR
      relationships. A literature search was conducted to identify published studies
      that report NMDR relationships with endocrine disruptors. Fifty-one experimental
      studies that investigated various effects associated with endocrine disruption
      elicited by many substances were selected. Scoring criteria were applied by
      adaptation of an approach previously used for identification of hormesis-type
      dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were
      categorized with this method as having a "moderate" to "high" level of
      plausibility for various effects. Numerous modes of action described in the
      literature can explain such phenomena. NMDR can arise from numerous molecular
      mechanisms such as opposing effects induced by multiple receptors differing by
      their affinity, receptor desensitization, negative feedback with increasing dose,
      or dose-dependent metabolism modulation. A stepwise decision tree was developed
      as a tool to standardize the analysis of NMDR relationships observed in the
      literature with the final aim to use these results in a Risk Assessment purpose.
      This decision tree was finally applied to studies focused on the effects of
      bisphenol A.

PMID- 25971435
TI  - Statistical and data reporting guidelines for the European Journal of Cardio
      Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery.
AB  - As part of the peer review process for the European Journal of Cardio-Thoracic
      Surgery (EJCTS) and the Interactive CardioVascular and Thoracic Surgery (ICVTS),
      a statistician reviews any manuscript that includes a statistical analysis. To
      facilitate authors considering submitting a manuscript and to make it clearer
      about the expectations of the statistical reviewers, we present up-to-date
      guidelines for authors on statistical and data reporting specifically in these
      journals. The number of statistical methods used in the cardiothoracic literature
      is vast, as are the ways in which data are presented. Therefore, we narrow the
      scope of these guidelines to cover the most common applications submitted to the
      EJCTS and ICVTS, focusing in particular on those that the statistical reviewers
      most frequently comment on. 

PMID- 25971436
TI  - Report details abuse of mentally ill inmates in US prisons.

PMID- 25971437
TI  - Exploring relation types for literature-based discovery.
AB  - OBJECTIVE: Literature-based discovery (LBD) aims to identify "hidden knowledge"
      in the medical literature by: (1) analyzing documents to identify pairs of
      explicitly related concepts (terms), then (2) hypothesizing novel relations
      between pairs of unrelated concepts that are implicitly related via a shared
      concept to which both are explicitly related. Many LBD approaches use simple
      techniques to identify semantically weak relations between concepts, for example,
      document co-occurrence. These generate huge numbers of hypotheses, difficult for
      humans to assess. More complex techniques rely on linguistic analysis, for
      example, shallow parsing, to identify semantically stronger relations. Such
      approaches generate fewer hypotheses, but may miss hidden knowledge. The authors
      investigate this trade-off in detail, comparing techniques for identifying
      related concepts to discover which are most suitable for LBD. MATERIALS AND
      METHODS: A generic LBD system that can utilize a range of relation types was
      developed. Experiments were carried out comparing a number of techniques for
      identifying relations. Two approaches were used for evaluation: replication of
      existing discoveries and the "time slicing" approach.(1) RESULTS: Previous LBD
      discoveries could be replicated using relations based either on document co
      occurrence or linguistic analysis. Using relations based on linguistic analysis
      generated many fewer hypotheses, but a significantly greater proportion of them
      were candidates for hidden knowledge. DISCUSSION AND CONCLUSION: The use of
      linguistic analysis-based relations improves accuracy of LBD without overly
      damaging coverage. LBD systems often generate huge numbers of hypotheses, which
      are infeasible to manually review. Improving their accuracy has the potential to
      make these systems significantly more usable.

PMID- 25971438
TI  - Changes in Depressive Symptoms and Incidence of First Stroke Among Middle-Aged
      and Older US Adults.
AB  - BACKGROUND: Although research has demonstrated that depressive symptoms predict
      stroke incidence, depressive symptoms are dynamic. It is unclear whether stroke
      risk persists if depressive symptoms remit. METHODS AND RESULTS: Health and
      Retirement Study participants (n=16 178, stroke free and noninstitutionalized at
      baseline) were interviewed biennially from 1998 to 2010. Stroke and depressive
      symptoms were assessed through self-report of doctors' diagnoses and a modified
      Center for Epidemiologic Studies - Depression scale (high was >=3 symptoms),
      respectively. We examined whether depressive symptom patterns, characterized
      across 2 successive interviews (stable low/no, onset, remitted, or stable high
      depressive symptoms) predicted incident stroke (1192 events) during the
      subsequent 2 years. We used marginal structural Cox proportional hazards models
      adjusted for demographics, health behaviors, chronic conditions, and attrition.
      We also estimated effects stratified by age (>=65 years), race or ethnicity (non
      Hispanic white, non-Hispanic black, Hispanic), and sex. Stroke hazard was
      elevated among participants with stable high (adjusted hazard ratio 2.14, 95% CI
      1.69 to 2.71) or remitted (adjusted hazard ratio 1.66, 95% CI 1.22 to 2.26)
      depressive symptoms compared with participants with stable low/no depressive
      symptoms. Stable high depressive symptom predicted stroke among all subgroups.
      Remitted depressive symptoms predicted increased stroke hazard among women
      (adjusted hazard ratio 1.86, 95% CI 1.30 to 2.66) and non-Hispanic white
      participants (adjusted hazard ratio 1.66, 95% CI 1.18 to 2.33) and was marginally
      associated among Hispanics (adjusted hazard ratio 2.36, 95% CI 0.98 to 5.67).
      CONCLUSIONS: In this cohort, persistently high depressive symptoms were
      associated with increased stroke risk. Risk remained elevated even if depressive
      symptoms remitted over a 2-year period, suggesting cumulative etiologic
      mechanisms linking depression and stroke.

PMID- 25971440
TI  - Essential protein SepF of mycobacteria interacts with FtsZ and MurG to regulate
      cell growth and division.
AB  - Coordinated bacterial cell septation and cell wall biosynthesis require formation
      of protein complexes at the sites of division and elongation, in a temporally
      controlled manner. The protein players in these complexes remain incompletely
      understood in mycobacteria. Using in vitro and in vivo assays, we showed that
      Rv2147c (or SepF) of Mycobacterium tuberculosis interacts with the principal
      driver of cytokinesis, FtsZ. SepF also interacts with itself both in vitro and in
      vivo. Amino acid residues 189A, 190K and 215F are required for FtsZ-SepF
      interaction, and are conserved across Gram-positive bacteria. Using Mycobacterium
      smegmatis as a surrogate system, we confirmed that sepFMSMEG is essential.
      Knockdown of SepF led to cell elongation, defective growth and failure of FtsZ to
      localize to the site of division, suggesting that SepF assists FtsZ localization
      at the site of division. Furthermore, SepF interacted with MurG, a peptidoglycan
      synthesizing enzyme, both in vitro and in vivo, suggesting that SepF could serve
      as a link between cell division and peptidoglycan synthesis. SepF emerges as a
      newly identified essential component of the cell division complex in
      mycobacteria. 

PMID- 25971439
TI  - Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with
      Infectious and Cardiac Deaths in the HEMO Study.
AB  - Longitudinal studies testing the relationship between repeated measures of
      vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac
      hospitalizations and death in hemodialysis patients have not been reported. We
      examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25
      dihydroxyvitamin D (1,25(OH)2D), and FGF23 serum levels and various clinical
      outcomes using time-dependent Cox regression models with repeated yearly measures
      and fixed-covariate Cox models with only baseline values after controlling for
      important clinical covariates in the HEMO study. During a median follow-up of 3
      years, 582 of the 1340 participants died, and 499 and 514 participants had a
      hospitalization or death attributed to infectious and cardiac causes,
      respectively. Patients in the highest 25(OH)D quartile had the lowest risk of
      infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95%
      confidence interval [95% CI], 0.49-0.89), cardiac events (HR, 0.71; 95% CI, 0.53
      0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34-0.62) in time-dependent
      analyses. No significant associations of 1,25(OH)2D with clinical outcomes were
      observed in time-dependent or fixed-covariate Cox models. In contrast, the
      highest FGF23 quartile was associated with a higher risk of infectious events
      (HR, 1.57 versus the lowest quartile; 95% CI, 1.13-2.18), cardiac events (HR,
      1.49; 95% CI, 1.06-2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07-2.12)
      in fixed-covariate Cox models. The addition of inflammation markers into the
      statistical models did not attenuate these associations. Thus, disordered mineral
      metabolism may affect outcomes in chronic hemodialysis patients. 

PMID- 25971441
TI  - Gene discovery and functional assessment of rare copy-number variants in
      neurodevelopmental disorders.
AB  - Rare copy-number variants (CNVs) are a significant cause of neurodevelopmental
      disorders. The sequence architecture of the human genome predisposes certain
      individuals to deletions and duplications within specific genomic regions. While
      assessment of individuals with different breakpoints has identified causal genes
      for certain rare CNVs, deriving gene-phenotype correlations for rare CNVs with
      similar breakpoints has been challenging. We present a comprehensive review of
      the literature related to genetic architecture that is predisposed to recurrent
      rearrangements, and functional evaluation of deletions, duplications and
      candidate genes within rare CNV intervals using mouse, zebrafish and fruit fly
      models. It is clear that phenotypic assessment and complete genetic evaluation of
      large cohorts of individuals carrying specific CNVs and functional evaluation
      using multiple animal models are necessary to understand the molecular genetic
      basis of neurodevelopmental disorders. 

PMID- 25971442
TI  - Anterior column realignment following lateral interbody fusion for sagittal
      deformity correction.
AB  - Degenerative and iatrogenic diseases may lead to loss of lordosis or even
      kyphotic thoracolumbar deformity and sagittal misalignment. Traditional surgery
      with three-column osteotomies is associated with important neurologic risks and
      postoperative morbidity. In a novel technique, the lateral transpsoas interbody
      fusion (LTIF) is complemented with the sacrifice of the anterior longitudinal
      ligament and anterior portion of the annulus followed by the insertion of a
      hyperlordotic interbody cage. This is a less invasive lateral technique named
      anterior column realignment (ACR) and aims to correct sagittal misalignment in
      adult spinal deformity (ASD), with or without the addition of minor posterior
      osteotomies. In this article, we provide an account of the evolution to the ACR
      technique, the literature, and the Brazilian experience in the treatment of adult
      spinal deformity with this novel advanced application of LTIF. In the presence of
      ASD, the risk-to-benefit ratio of a surgical correction must be evaluated. Less
      invasive surgical strategies can be alternatives to treat the deformity and
      provide better quality of life to the patient. ACR is an advanced application of
      lateral transpsoas approach, up to date has shown to be reliable and effective
      when used for ASD, and may minimize complications and morbidity from traditional
      surgical procedures. Long-term follow-up and comparative studies are needed to
      evaluate real benefit. 

PMID- 25971443
TI  - Dual phosphodiesterase type 5 inhibitor therapy for refractory pulmonary arterial
      hypertension: a pilot study.
AB  - BACKGROUND: Recent vasodilating drugs have improved prognosis of Pulmonary
      arterial hypertension (PAH). Some reports describe the merits of combination
      therapies for PAH, and this study evaluated the efficacy and safety of
      phosphodiesterase type 5 inhibitors (PDE5i) combination therapy, using sildenafil
      and tadalafil, for multi-drug-resistant PAH. METHODS: We retrospectively analyzed
      7 consecutive refractory patients with PAH administered either sildenafil 60 mg
      or tadalafil 40 mg as well as both ERA and prostanoid as combination therapies.
      All were started on the dual PDE5i (sildenafil and tadalafil at maximum dose).
      RESULTS: Treatment was generally well tolerated without severe adverse events. On
      completion of the study, the seven patients received right heart catheterization
      and the 6-minute walk test (6WMT) 9.6 +/- 1.4 months after initiation of the dual
      PDE5i therapy, showing significant improvements in hemodynamic parameters and
      exercise tolerance. Mean pulmonary arterial pressure and pulmonary vascular
      resistance decreased from 47.9 +/- 9.7 to 41.7 +/- 9.2 mmHg (P = 0.004) and 9.3
      +/- 2.7 to 6.7 +/- 2.9 mmHg (P = 0.018), respectively. Cardiac index and 6MWT
      also increased from 2.8 +/- 0.9 to 3.1 +/- 0.8 L/min/m(2) (P = 0.026) and 353 +/-
      60 to 382 +/- 62 m (P = 0.014), respectively. CONCLUSION: The findings support
      dual PDE5i therapy as a new treatment option for refractory PAH.

PMID- 25971444
TI  - The difference between Asian and Western in the effect of LDL-C lowering therapy
      on coronary atherosclerotic plaque: a meta-analysis report.
AB  - BACKGROUND: The different effects of LDL-C levels and statins therapy on coronary
      atherosclerotic plaque between Western and Asian remain to be settled. METHODS:
      PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Sep. 2014
      for randomized controlled or blinded end-points trials assessing the effects of
      LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in
      patients with coronary heart disease by intravascular ultrasound. The
      significance of plaques regression was assessed by computing standardized mean
      difference (SMD) of the volume of CAP between the baseline and follow-up.
      RESULTS: Twenty trials (ten in the West and ten in Asia) were identified. For
      Westerns, Mean lowering LDL-C by 49.4% and/or to level 61.9 mg/dL in the group of
      patients with baseline mean LDL-C 123.2 mg/dL could significantly reduce the
      volume of CAP at follow up (SMD -0.156 mm(3), 95% CI -0.248 ~ -0.064, p = 0.001).
      LDL-C lowering by rosuvastatin (mean 40 mg daily) could significantly decrease
      the volumes of CAP at follow up. For Asians, Mean lowering LDL-C by 36.1% and/or
      to level 84.0 mg/dL with baseline mean LDL-C 134.2 mg/dL could significantly
      reduce the volume of CAP at follow up (SMD -0.211 mm(3), 95% CI -0.331 ~ -0.092,
      p = 0.001). LDL-C lowering by rosuvastatin (mean 14.1 mg daily) and atorvastatin
      (mean 18.9 mg daily) could significantly decrease the volumes of CAP at follow
      up. CONCLUSIONS: There was a different effect of LDL-C lowering on CAP between
      Westerns and Asians. For regressing CAP, Asians need lower dosage of statins or
      lower intensity LDL-C lowering therapy than Westerns.

PMID- 25971445
TI  - The respiratory health of urban indigenous children aged less than 5 years: study
      protocol for a prospective cohort study.
AB  - BACKGROUND: Despite the burden of acute respiratory illnesses (ARI) among
      Aboriginal and Torres Strait Islander children being a substantial cause of
      childhood morbidity and associated costs to families, communities and the health
      system, data on disease burden in urban children are lacking. Consequently
      evidence-based decision-making, data management guidelines, health resourcing for
      primary health care services and prevention strategies are lacking. This study
      aims to comprehensively describe the epidemiology, impact and outcomes of ARI in
      urban Aboriginal and Torres Strait Islander children (hereafter referred to as
      Indigenous) in the greater Brisbane area. METHODS/DESIGN: An ongoing prospective
      cohort study of Indigenous children aged less than five years registered with a
      primary health care service in Northern Brisbane, Queensland, Australia. Children
      are recruited at time of presentation to the service for any reason. Demographic,
      epidemiological, risk factor, microbiological, economic and clinical data are
      collected at enrolment. Enrolled children are followed for 12 months during which
      time ARI events, changes in child characteristics over time and monthly nasal
      swabs are collected. Children who develop an ARI with cough as a symptom during
      the study period are more intensely followed-up for 28 (+/-3) days including
      weekly nasal swabs and parent completed cough diary cards. Children with
      persistent cough at day 28 post-ARI are reviewed by a paediatrician. DISCUSSION:
      Our study will be one of the first to comprehensively evaluate the natural
      history, epidemiology, aetiology, economic impact and outcomes of ARIs in this
      population. The results will inform studies for the development of evidence-based
      guidelines to improve the early detection, prevention and management of chronic
      cough and setting of priorities in children during and after ARI. TRIAL
      REGISTRATION: Australia New Zealand Clinical Trial Registry Registration Number:
      12614001214628 . Registered 18 November 2014.

PMID- 25971446
TI  - Oxidative DNA damage induced by metabolites of chloramphenicol, an antibiotic
      drug.
AB  - Chloramphenicol (CAP) was an old antimicrobial agent. However, the use of CAP is
      limited because of its harmful side effects, such as leukemia. The molecular
      mechanism through which CAP has been strongly correlated with leukemogenesis is
      still unclear. To elucidate the mechanism of genotoxicity, we examined DNA damage
      by CAP and its metabolites, nitroso-CAP (CAP-NO), N-hydroxy-CAP (CAP-NHOH), using
      isolated DNA. CAP-NHOH have the ability of DNA damage including 8-oxo-7,8-dihydro
      2'-deoxyguanosine formation in the presence of Cu(II), which was greatly enhanced
      by the addition of an endogenous reductant NADH. CAP-NO caused DNA damage in the
      presence of Cu(II), only when reduced by NADH. NADH can non-enzymatically reduce
      the nitroso form to hydronitroxide radicals, resulting in enhanced generation of
      reactive oxygen species followed by DNA damage through the redox cycle.
      Furthermore, we also studied the site specificity of base lesions in DNA treated
      with piperidine or formamidopyrimidine-DNA glycosylase, using (32)P-5'-end
      labeled DNA fragments obtained from the human tumor suppressor gene. CAP
      metabolites preferentially caused double base lesion, the G and C of the ACG
      sequence complementary to codon 273 of the p53 gene, in the presence of NADH and
      Cu(II). Therefore, we conclude that oxidative double base lesion may play a role
      in carcinogenicity of CAP. 

PMID- 25971447
TI  - Oxidative stress in myelin sheath: The other face of the extramitochondrial
      oxidative phosphorylation ability.
AB  - Oxidative phosphorylation (OXPHOS) is not only the main source of ATP for the
      cell, but also a major source of reactive oxygen species (ROS), which lead to
      oxidative stress. At present, mitochondria are considered the organelles
      responsible for the OXPHOS, but in the last years we have demonstrated that it
      can also occur outside the mitochondrion. Myelin sheath is able to conduct an
      aerobic metabolism, producing ATP that we have hypothesized is transferred to the
      axon, to support its energetic demand. In this work, spectrophotometric,
      cytofluorimetric, and luminometric analyses were employed to investigate the
      oxidative stress production in isolated myelin, as far as its respiratory
      activity is concerned. We have evaluated the levels of malondialdehyde (MDA) and
      4-hydroxynonenal (4-HNE), markers of lipid peroxidation, as well as of hydrogen
      peroxide (H2O2), marker of ROS production. To assess the presence of endogenous
      antioxidant systems, superoxide dismutase, catalase, and glutathione peroxidase
      activities were assayed. The effect of certain uncoupling or antioxidant
      molecules on oxidative stress in myelin was also investigated. We report that
      isolated myelin produces high levels of MDA, 4-HNE, and H2O2, likely through the
      pathway composed by Complex I-III-IV, but it also contains active superoxide
      dismutase, catalase, and glutathione peroxidase, as antioxidant defense.
      Uncoupling compounds or Complex I inhibitors increase oxidative stress, while
      antioxidant compounds limit ROS generation. Data may shed new light on the role
      of myelin sheath in physiology and pathology. In particular, it can be presumed
      that the axonal degeneration associated with myelin loss in demyelinating
      diseases is related to oxidative stress caused by impaired OXPHOS. 

PMID- 25971448
TI  - Feasibility and toxicity of adjuvant chemotherapy using S-1 granules for local
      advanced squamous cell carcinoma of the head and neck.
AB  - S-1 granulated powder has recently been released to the market as an additional
      format to that of the capsule. Patients who previously found it difficult to
      swallow the capsules are now able to take S-1 in powder form. This study
      evaluated the feasibility of S-1 granulated powder as adjuvant chemotherapy for
      advanced head and neck cancer. S-1 was orally administered for 2  weeks, followed
      by 1  week of rest (one course) for 12  months (16 courses). Twenty-four stage
      III and IV head and neck cancer patients were enrolled in this study. In total,
      10 (47.6%) of the patients follow the planned schedule and dose. Severe adverse
      events were observed in 22 patients (91.7%), whereas no grade 4 adverse events
      were observed. S-1 granulated powder should be presented as an additional option
      for the treatment of head and neck cancer, especially for patients experiencing
      difficulty in swallowing oral medications.

PMID- 25971449
TI  - Allied health growth: what we do not measure we cannot manage.
AB  - BACKGROUND: Data describing the Australian allied health workforce is inadequate
      and so insufficient for workforce planning. National health policy reform
      requires that health-care models take into account future workforce requirements,
      the distribution and work contexts of existing practitioners, training needs,
      workforce roles and scope of practice. Good information on this workforce is
      essential for managing services as demands increase, accountability of
      practitioners, measurement of outcomes and benchmarking against other
      jurisdictions. A comprehensive data set is essential to underpin policy and
      planning to meet future health workforce needs. DISCUSSION: Some data on allied
      health professions is managed by the Australian Health Practitioner Regulation
      Agency; however, there is limited information regarding several core allied
      health professions. A global registration and accreditation scheme recognizing
      all allied health professions might provide safeguards and credibility for
      professionals and their clients. Arguments are presented about inconsistencies
      and voids in the available information about allied health services. Remedying
      these information deficits is essential to underpin policy and planning for
      future health workforce needs. We make the case for a comprehensive national data
      set based on a broad and inclusive sampling process across the allied health
      population.

PMID- 25971450
TI  - Assessment of absolute Tc-99m tetrofosmin retention in the myocardium as an index
      of myocardial blood flow and coronary flow reserve by gated-SPECT/CT: a
      feasibility study.
AB  - OBJECTIVE: Estimation of myocardial blood flow (MBF) and coronary flow reserve
      (CFR) by SPECT myocardial perfusion imaging (MPI) remains challenging. Our aim
      was to approximate MBF and CFR by quantifying the absolute Tc-99m tetrofosmin
      retention in the myocardium via gated-SPECT/CT MPI. METHODS: Tracer retention was
      calculated on the basis of the microsphere kinetic model and served as an index
      of MBF at stress and rest (sMBFi, rMBFi). CFR was given by the sMBFi/rMBFi ratio.
      A planar first-pass acquisition during dipyridamole stress and at rest provided
      the data for tracer input determination. The input was represented by the
      integral of a gamma variate fitted on the time-activity curve of the left
      ventricle. Gated-SPECT/CT was performed 1 h post tracer injection and myocardial
      activity was measured in attenuation-corrected transaxial slices by a threshold
      VOI. The input was also compensated for tissue attenuation by measuring the
      distance from the centre of the left ventricle to the body surface on fused
      SPECT/CT slices. Input and uptake results were adjusted for planar-SPECT counting
      geometry differences by the aid of a phantom experiment. Thirty-nine subjects
      with low probability of coronary artery disease (CAD), age lower than 75 years
      and normal MPI (control group) were compared with 57 patients with documented CAD
      (CAD group). RESULTS: CFR and sMBFi values of CAD patients (1.39 +/- 0.37 and
      1.42 +/- 0.35 ml/min/g) were considerably lower (p < 0.0001) than controls (1.68
      +/- 0.25 and 1.72 +/- 0.37 ml/min/g). Significant difference in CFR (p = 0.03)
      was also noted between CAD patients with normal MPI (1.48 +/- 0.38) and controls.
      However, sMBFi managed to discriminate certain CAD subgroups (normal
      MPI/ischemia/scar/scar and ischemia) more efficiently than CFR. Maximum heart
      rate-blood pressure product (RPP) during stress was an independent predictor of
      sMBFi and CFR. The other independent CFR correlates were resting RPP and diabetes
      mellitus, while sMBFi was associated with age, sex, smoking, and stress perfusion
      defects. CONCLUSIONS: Despite the low myocardial extraction fraction of Tc-99m
      tetrofosmin, an approximation of MBF and CFR is feasible with gated-SPECT/CT MPI.
      These flow indices together were able to discriminate CAD patients from controls
      and stratify different patient subgroups.

PMID- 25971452
TI  - Microalbuminuria and left ventricular hypertrophy among newly diagnosed black
      African hypertensive patients: a cross sectional study from a tertiary hospital
      in Uganda.
AB  - BACKGROUND: Microalbuminuria is an early manifestation of kidney damage and
      independently predicts cardiovascular disease (CVD). Left ventricular hypertrophy
      (LVH) is also an early marker of cardiac manifestation of target organ damage
      among hypertensive patients. The prognostic significance of microalbuminuria and
      its correlation with left ventricular hypertrophy has not been extensively
      studied in African adult hypertensive populations. This study aimed at
      determining the prevalence of microalbuminuria, LVH in patients with
      microalbuminuria and the correlation between microalbuminuria and LVH among newly
      diagnosed black adult hypertensive patients attending a large outpatient
      hypertension clinic or admitted on the cardiology ward at Mulago national
      referral and teaching hospital and Uganda Heart Institute in Kampala, Uganda.
      METHODS: In this cross-sectional study, 256 newly diagnosed eligible black adult
      hypertensive patients attending the outpatient hypertension clinic or admitted on
      the cardiology ward at Mulago national referral and teaching hospital and the
      Uganda Heart Institute, Kampala Uganda were consecutively recruited over a period
      of 5 months. Data on socio-demographics, clinical and laboratory findings of the
      study participants was collected using a pre tested questionnaire. Two spot urine
      samples were collected to assess for microalbuminuria. Echocardiography (ECHO)
      was done to assess for the left ventricular mass index using the formula of
      Teicholz as evidence for early hypertensive heart disease. RESULTS: The mean
      age/standard deviation of the study participants was 54.3 +/- 6.2 years with a
      female predominance (162, 63.3%). The prevalence of microalbuminuria among newly
      diagnosed hypertensive patients was 39.5%. The prevalence of LVH among patients
      with microalbuminuria was found to be 17%. There was a positive correlation
      between microalbuminuria and left ventricular hypertrophy among the newly
      diagnosed adult hypertensive patients at Mulago Hospital (r = 0.185, p = 0.003).
      CONCLUSIONS: This study demonstrates that microalbuminuria is highly prevalent
      among newly diagnosed black hypertensive patients and in the presence of LVH.
      There is also a positive correlation between microalbuminuria and LVH among newly
      diagnosed hypertensive patients. Since it is a less costly and readily available
      test, it can be used to predict presence of LVH especially in resource limited
      settings where ECHO services are not readily available.

PMID- 25971451
TI  - Prospective, longitudinal, multi-modal functional imaging for radical chemo-IMRT
      treatment of locally advanced head and neck cancer: the INSIGHT study.
AB  - BACKGROUND: Radical chemo-radiotherapy (CRT) is an effective organ-sparing
      treatment option for patients with locally advanced head and neck cancer (LAHNC).
      Despite advances in treatment for LAHNC, a significant minority of these patients
      continue to fail to achieve complete response with standard CRT. By constructing
      a multi-modality functional imaging (FI) predictive biomarker for CRT outcome for
      patients with LAHNC we hope to be able to reliably identify those patients at
      high risk of failing standard CRT. Such a biomarker would in future enable CRT to
      be tailored to the specific biological characteristics of each patients' tumour,
      potentially leading to improved treatment outcomes. METHODS/DESIGN: The INSIGHT
      study is a single-centre, prospective, longitudinal multi-modality imaging study
      using functional MRI and FDG-PET/CT for patients with LAHNC squamous cell
      carcinomas receiving radical CRT. Two cohorts of patients are being recruited:
      one treated with, and another treated without, induction chemotherapy. All
      patients receive radical intensity modulated radiotherapy with concurrent
      chemotherapy. Patients undergo functional imaging before, during and 3 months
      after completion of radiotherapy, as well as at the time of relapse, should that
      occur within the first two years after treatment. Serum samples are collected
      from patients at the same time points as the FI scans for analysis of a panel of
      serum markers of tumour hypoxia. DISCUSSION: The primary aim of the INSIGHT study
      is to acquire a prospective multi-parametric longitudinal data set comprising
      functional MRI, FDG PET/CT, and serum biomarker data from patients with LAHNC
      undergoing primary radical CRT. This data set will be used to construct a
      predictive imaging biomarker for outcome after CRT for LAHNC. This predictive
      imaging biomarker will be used in future studies of functional imaging based
      treatment stratification for patients with LAHNC. Additional objectives are:
      defining the reproducibility of FI parameters; determining robust methods for
      defining FI based biological target volumes for IMRT planning; creation of a
      searchable database of functional imaging data for data mining. The INSIGHT study
      will help to establish the role of FI in the clinical management of LAHNC. TRIAL
      REGISTRATION: NCRI H&N CSG ID 13860.

PMID- 25971453
TI  - Selectively false-positive radionuclide scan in a patient with sarcoidosis and
      papillary thyroid cancer: a case report and review of the literature.
AB  - BACKGROUND: Radioiodine and Tc-99 m pertechnetate scans are routinely relied upon
      to detect metastasis in papillary thyroid cancer; false-positive scans are
      relatively rare. To our knowledge, no published reports exist of sarcoidosis
      causing such selectively false-positive scans. METHODS: We present a case of a 41
      year-old woman with known metastatic papillary thyroid cancer (T1bN1aMx) in whom
      sarcoidosis-affected cervical and mediastinal lymph nodes demonstrated uptake of
      thyroid-targeting radionuclides. Only the minority of these nodes demonstrated
      radionuclide uptake, raising the suspicion of adjacent or coexisting sarcoid and
      metastatic involvement. Selective uptake of thyroid-targeted radionuclides by
      isolated sarcoidosis is, to our knowledge, a previously undocumented occurrence.
      RESULTS: Biopsies of uptake-negative mediastinal nodes revealed sarcoidosis.
      Pathology from a subsequent neck dissection excising uptake-positive cervical
      nodes also showed sarcoidosis, with no coinciding malignancy. CONCLUSIONS: We
      document a case of sarcoidosis causing a selectively false-positive thyroid
      scintigraphy scan. It is useful for clinicians to be aware of potential false
      positives and deceptive patterns on radionuclide scans when managing patients
      with both well-differentiated thyroid cancer and a co-existing disease affecting
      the nodal basins draining the thyroid gland.

PMID- 25971454
TI  - [Exercise scenario of a highly contagious, life-threatening disease in
      intercontinental aviation : a case report in the context of the International
      Health Regulations (IHR)].
AB  - BACKGROUND: The International Health Regulations (IHR) 2005 were conformed to
      German law on July 20, 2007 and described in detail by the Implementing Act (IHR
      DG). According to these legal bases, "designated airports" must maintain special
      capacities for protection against health threats, and are also responsible for
      performing regular IHR exercises. OBJECTIVES: Representation of the optimization
      of established operational concepts of various professions to manage infectious
      biological threats without obstruction of international travel, and mediation of
      experience to IHR professionals. MATERIALS AND METHODS: An exercise based on the
      case scenario of a travel-related febrile illness was performed at Munich
      International Airport on November 11, 2013. Preparations took 6 months and the
      exercise itself lasted nearly 12 h. The follow-up lasted an additional 9 months.
      A qualitative and quantitative evaluation of the exercise was completed. RESULTS:
      From an Individual Medicine and Public Health perspective, modular work
      structures and risk communication functioned adequately. The medical examination
      of passengers was also well managed. Areas requiring further optimization
      included arrival/departure times of external actors, transport of the index
      patient to hospital and protective measures for individual participants. Overall,
      a defined biological threat scenario representing a double infection with two
      highly pathogenic germs was handled satisfactorily without affecting
      international air travel. CONCLUSIONS: Modular supply components are an effective
      and forward-looking means in protection against threats occurring at airports.
      Key success factors include sufficient staff mobility, immediate self-protection
      of actors involved, effective risk communication and a strong overall
      coordination and monitoring of the situation.

PMID- 25971456
TI  - Up-to-date information is in your hands: online teaching.

PMID- 25971455
TI  - Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile
      leukodystrophy.
AB  - Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative
      disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant
      presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole
      exome sequencing, and functional studies were used to define the underlying
      molecular defect. Respiratory chain studies in skeletal muscle isolated from the
      proband revealed a combined deficiency of complexes I and II. In addition,
      western blotting indicated lack of protein lipoylation. The combination of these
      findings was suggestive for a defect in the iron-sulfur (Fe/S) protein assembly
      pathway. SNP array identified loss of heterozygosity in large chromosomal
      regions, covering the NFU1 and BOLA3, and the IBA57 and ABCB10 candidate genes,
      in 2p15-p11.2 and 1q31.1-q42.13, respectively. A homozygous c.436C > T
      (p.Arg146Trp) variant was detected in IBA57 using whole exome sequencing.
      Complementation studies in a HeLa cell line depleted for IBA57 showed that the
      mutant protein with the semi-conservative amino acid exchange was unable to
      restore the biochemical phenotype indicating a loss-of-function mutation of
      IBA57. In conclusion, defects in the Fe/S protein assembly gene IBA57 can cause
      autosomal recessive neurodegeneration associated with progressive leukodystrophy
      and fatal outcome at young age. In the affected patient, the biochemical
      phenotype was characterized by a defect in the respiratory chain complexes I and
      II and a decrease in mitochondrial protein lipoylation, both resulting from
      impaired assembly of Fe/S clusters.

PMID- 25971458
TI  - The inferomedial patellar protuberance and medial patellar ossicle in patellar
      instability.
AB  - PURPOSE: The purpose of the study was to define the frequency of an inferomedial
      patellar protuberance in patients presenting to a specialist Patella Clinic and
      to characterise the clinical and radiological features as well the association
      between the inferomedial patellar protuberance and the medial patellar ossicle.
      METHODS: A cohort of 163 patients (166 knees) was reviewed from a prospectively
      collected clinical database and radiological imaging. This included a record of
      patellar tracking. RESULTS: An inferomedial patellar protuberance was found in 62
      (37 %) knees. A medial patellar ossicle was noted in 56 (34 %) knees. In all, an
      inferomedial patellar protuberance or medial patellar ossicle or both was found
      in 90 (54 %) knees. The association between inferomedial patellar protuberance
      and significant trochlear dysplasia was highly significant (p = 0.01), but not
      for the medial patellar ossicle (n.s.). The presence of an inferomedial patellar
      protuberance was significantly less likely in patients with hypermobility
      syndrome (p = 0.001); however, there was no significant association between
      hypermobility syndrome and medial patellar ossicle (n.s.), or the presence of
      either or both an inferomedial patellar protuberance and medial patellar ossicle
      (n.s.). All patients with a clunk at 20 degrees -30 degrees  flexion had
      significant trochlear dysplasia and an inferomedial patellar protuberance.
      CONCLUSION: Radiological changes consistent with an inferomedial patellar
      protuberance were found in about one-third of patients presenting to a specialist
      Patella Clinic. Patellar maltracking and a clunk at 20 degrees -30 degrees 
      flexion are associated with significant trochlear dysplasia plus an inferomedial
      patellar protuberance. If undertaking an operative correction, both deformities
      should be considered in order to avoid joint incongruity. LEVEL OF EVIDENCE: III.

PMID- 25971457
TI  - Functional biomechanical performance of a novel anatomically shaped polycarbonate
      urethane total meniscus replacement.
AB  - PURPOSE: To evaluate the functional biomechanical performance of a novel
      anatomically shaped, polycarbonate urethane total meniscus implant. METHODS: Five
      human cadaveric knees were flexed between 0 degrees  and 90 degrees  under
      compressive loads mimicking a squat movement. Anteroposterior (AP) laxity tests
      were performed in 30 degrees  and 90 degrees  flexion. Meniscal kinematics and
      knee laxity were quantified using roentgen stereophotogrammetric analysis. Tibial
      cartilage contact mechanics were determined in 90 degrees  flexion. Measurements
      were repeated for the native medial meniscus, the implant, after total medial
      meniscectomy and allograft transplantation. RESULTS: The implant and allograft
      displayed increased posterior and medial displacements compared to the native
      meniscus, yet no differences were found between the implant and allograft.
      Meniscal condition did not affect rotational laxity. Compared to the native
      joint, AP laxity for the implant was increased in 30 degrees  flexion, but not in
      90 degrees . The implant reduced the mean contact pressure compared to
      meniscectomy but could not restore contact pressures to native meniscus levels.
      Compared to the native meniscus, the implant significantly increased the peak
      pressure, while the contact area was reduced. Contact mechanics of the implant
      and allograft were never statistically different. CONCLUSIONS: Biomechanical
      performance was similar for the implant and allograft. However, both meniscal
      replacements could not restore outcomes to native meniscus levels or sufficiently
      improve outcomes after meniscectomy. This was presumably caused by the mobility
      allowed by the suture-only horn fixation. The similarity of implant and allograft
      performance suggests that the novel implant has the biomechanical potential to
      serve as an alternative to meniscal allograft transplantation.

PMID- 25971460
TI  - Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity.
AB  - Sevoflurane, one of the most commonly used volatile anesthetics in clinical
      treatment, has been shown to induce a widespread increase in brain apoptosis.
      However, the underlying mechanism is still unknown. Sestrin 2 has been recently
      shown to regulate intracellular reactive oxygen species (ROS) levels and play a
      crucial role in p53-dependent antioxidant defenses. In this study, our results
      indicated that administration of Sevoflurane elevated the gene and protein
      expression of Sestrin-2 in a dose dependent manner in human neuroblastoma M17
      cells. It was shown that silence of Sestrin-2 by small RNA interference (siRNA)
      ominously exacerbated the increase in intracellular ROS and reduction of SOD
      activity induced by Sevoflurane treatment. Notably, knockdown of Sestrin-2 in M17
      cells significantly increases the number of apoptotic cells after treatment with
      Sevoflurane. Mechanistically, we also found that Sevoflurane treatment resulted
      in a reduced amount of the cytosolic anti-apoptotic protein Bcl-2 but an
      increased amount of Bax, which was exacerbated by knockdown of Sestrin-2. In
      addition, knockdown of Sestrin-2 remarkably increased the elevated cleaved
      Caspase-3 expression. Finally, we showed that the induction of Sestrin-2 by
      Sevoflurane was mediated by p53. These results suggest that the suppressive
      effects of Sestrin-2 on neuroapoptosis against the Sevoflurane anesthesia in
      neuronal cells might be associated with modulation of mitochondrial pathway. 

PMID- 25971459
TI  - Long-term outcome after all-inside meniscal repair using the RapidLoc system.
AB  - PURPOSE: The purpose of the present study was to evaluate the outcome at a
      minimum of 7 years following meniscal repair using the RapidLoc (suture anchor)
      system. It was hypothesized that most patients would have an intact meniscus, as
      has been reported in several short- and medium-term studies. METHODS: In the time
      period from 2002 to 2007, all patients with a vertical longitudinal tear of the
      meniscus that was judged to be repairable were treated with rasping of the tear
      area and nearby parameniscal synovium and fixation of the torn part with the use
      of RapidLoc implants. Using a surgeon-administered form, baseline information
      about the arthroscopic findings and procedures performed was recorded (at the
      time of surgery). A median 10-year (range 7-12 years) follow-up was conducted in
      2014-2015, and surgical procedures to the knee following the (index) meniscal
      repair were registered. Treatment failure was defined as a new surgical procedure
      to the same meniscus. RESULTS: At the time of follow-up, 39 out of 82 patients
      (48 %) had undergone further surgery to the repaired meniscus (failures). Nine of
      these occurred within the first 6 months after surgery, 21 within the first 12
      months and 26 within the first 24 months. Thus, the failure rate was 11 % at 6
      months, 23 % at 12 months and 28 % at 2 years. One-third (N = 13) of the failures
      occurred 2 years or later after the (index) meniscal repair. CONCLUSIONS: Long
      term results of meniscal repair using the RapidLoc implants were found to be poor
      with a high failure rate. In a large proportion of the cases, re-rupture appeared
      several years after the index surgery, and a commonly used follow-up period of 2
      years would therefore fail to detect them. In the day-by-day clinical work, of
      interest to orthopaedic surgeons is that meniscal repair using an all-inside
      technique similar to the one used by the authors may not solve the problem in the
      long run. LEVEL OF EVIDENCE: IV.

PMID- 25971461
TI  - Opioid Prescribing and Potential Overdose Errors Among Children 0 to 36 Months
      Old.
AB  - OBJECTIVE: To estimate the frequency of potential overdoses among outpatient
      opioid-containing prescriptions. METHOD: Using 11 years of outpatient Medicaid
      prescription data, we compared opioid dose dispensed (observed) versus expected
      dose to estimate overdose error frequencies. A potential overdose was defined as
      any preparation dispensed that was >110% of expected based on imputed, 97th
      percentile weights. RESULTS: There were 59 536 study drug prescriptions to
      children 0 to 36 months old. Overall, 2.7% of the prescriptions contained
      potential overdose quantities, and the average excess amount dispensed was 48%
      above expected. Younger ages were associated with higher frequencies of potential
      overdose. For example, 8.9% of opioid prescriptions among infants 0 to 2 months
      contained potential overdose quantities, compared with 5.7% among infants 3 to 5
      months old, 3.6% among infants 6 to 11 months old, and 2.3% among children >12
      months (P < .0001). CONCLUSIONS: Opioid prescriptions for infants and children
      routinely contained potential overdose quantities.

PMID- 25971462
TI  - Enhancing Patient Safety in Pediatric Primary Care: Implementing a Patient Safety
      Curriculum.
AB  - OBJECTIVE: We developed and implemented a patient safety (PS) curriculum targeted
      at clinicians and nonclinical office practice staff within a large primary care
      pediatric network. METHODS: Curricular content was informed by medical
      literature, local PS experts, and malpractice claims data. Sessions were centered
      on illustrative closed malpractice cases or informed by identified safety events.
      Participants provided subjective responses to the postsession evaluations.
      RESULTS: Invited participants from 12 practices included both clinical and
      nonclinical practice staff (up to 24 attendees per session). Participants
      reported that they were confident in their knowledge and skills. Several
      participants engaged in improvement projects that included active surveillance of
      high-risk patients, improvements in referral and test result management
      processes, and the distribution of patient educational materials. CONCLUSIONS: We
      successfully developed and implemented a multifaceted PS curriculum for pediatric
      providers. Participants enjoyed the sessions and several engaged in new PS
      projects as a result of the program.

PMID- 25971463
TI  - Hip Dysfunction and Quality of Life in Patients With Sickle Cell Disease.
AB  - OBJECTIVE: To evaluate the influence of hip dysfunction on quality of life of
      pediatric patients with sickle cell disease (SCD). METHODS: Clinical demographic,
      Charnley hip score, Barthel scale and Pediatric Quality of Life Inventory (PedsQL
      4.0) questionnaires were used. RESULTS: Seventeen patients were placed into the
      group "with hip dysfunction," and 54 into the group "without hip dysfunction."
      The group "with hip dysfunction" had a higher average age (P = .026), weight (P =
      .029), and height (P = .019) than the group "without hip dysfunction." There was
      also a higher prevalence of hip trauma (P = .05) and pain (P = .00). The study
      demonstrated that hip dysfunction negatively influenced quality of life in the
      physical activity (P = .11) and psychosocial (P = .003) domains. CONCLUSION: Hip
      dysfunction and previous hip trauma negatively influenced quality of life,
      especially in the physical activity and psychosocial domains.

PMID- 25971464
TI  - Designing a knowledge translation mentorship program to support the
      implementation of evidence-based innovations.
AB  - BACKGROUND: Healthcare professionals require training in knowledge translation
      (KT) to implement evidence-based healthcare innovations. Mentorship is an
      effective training strategy that could be used to develop KT capacity but it has
      largely been used to train clinicians. The purpose of this study was to explore
      preferences for KT mentorship design. METHODS: Interviews were conducted with 54
      Canadian researchers and research users who varied by profession, department,
      career stage and sex. Participants were asked about KT needs, views on mentorship
      as a strategy to develop KT capacity, and suggestions for program design.
      Grounded theory technique and thematic analysis were used to collect and analyse
      data. RESULTS: Participants uniformly expressed interest in mentorship over other
      forms of learning about KT because it would provide credible, tailored
      information when needed. A variety of options for program content, format and
      delivery were recommended, suggesting the need for flexibility according to KT
      needs. Leadership, infrastructure, culture change and incentives may also be
      needed to foster KT mentorship. Views were mixed on whether mentors should be KT
      experts or subject or clinical experts with KT experience, and embedded in, or
      external to organizations. CONCLUSIONS: These findings can be used to develop or
      evaluate KT mentoring programs. Further research is needed to evaluate different
      models in which the mentor may be an internal or external KT expert or subject
      expert with experience in KT, and establish the core curriculum of a training
      program specific to KT and how it could best be reinforced with mentoring.

PMID- 25971468
TI  - Challenging times.

PMID- 25971465
TI  - Endocrine therapy adherence: a cross-sectional study of factors affecting
      adherence and discontinuation of therapy.
AB  - BACKGROUND/AIMS: Adjuvant endocrine therapy for at least 5 years improves
      oncological outcomes in oestrogen receptor-positive breast cancer. Adherence
      rates to prescribed endocrine therapy are low and the search for modifiable
      causes of this continues. The aim of this study was to assess adherence rates in
      an Irish cohort of breast cancer patients prescribed adjuvant endocrine therapy
      and to assess modifiable factors associated with suboptimal adherence. METHODS: A
      cross-sectional anonymous survey was performed on 261 patients currently
      prescribed endocrine therapy. Data were collected regarding demographics,
      treatment, social and emotional factors and medication side effects. Each patient
      completed a medication adherence score and provided information about
      discontinuation of therapy and reasons for same. RESULTS: Only 67.8 % of patients
      assessed demonstrated complete medication adherence on the medication adherence
      scale. Twenty-nine patients (10.9 %) permanently stopped taking their prescribed
      endocrine therapy. Suboptimal adherence was more likely in younger patients (p <
      0.001), those in employment (p = 0.005), those who experienced side effects (p =
      0.006), those who perceived themselves to have low levels of emotional support (p
      < 0.001) and those who use the internet to read about their illness (p = 0.003).
      CONCLUSIONS: Endocrine therapy adherence is suboptimal in almost one-third of
      patients in our cohort. Appropriate assessment and management of side effects and
      negative emotions, combined with direction of patients to accurate internet
      sources of information, could help improve endocrine therapy adherence in women
      with early-stage breast cancer.

PMID- 25971466
TI  - The involvement of central beta-endorphin in the cardioprotective effects of
      remote preconditioning mediated by the intracerebroventricular administration of
      morphine.
AB  - BACKGROUND: Opioids can mimic the effects of remote cardiac preconditioning and
      mediate a subsequent reduction in myocardial infarct size. AIM: This study
      investigated the role of beta-endorphin (beta-EP) in intracerebroventricular
      morphine cardioprotection. METHODS: Anesthetized, open-chest, male Sprague-Dawley
      rats were assigned to 1 of 9 treatment groups 3 days after
      intracerebroventricular catheter placement. Remote preconditioning was induced
      with 3 MUg/kg of morphine. The beta-EP antagonist was administered via
      intracerebroventricular or intravenous routes either 10 min before or immediately
      after morphine or saline administration. Ischemia-reperfusion injury was caused
      by 30 min of left coronary artery occlusion followed by 120 min of reperfusion.
      The infarct size, as a percentage of the area at risk, was determined by 2,3,5
      triphenyltetrazolium staining. Radioimmunoassay and immunoreactivity were used to
      determine the beta-EP levels in the serum and brain. RESULTS:
      Intracerebroventricular administration of beta-EP antiserum (AEP) after morphine
      administration attenuated the cardioprotective effects of remote preconditioning.
      The addition of intravenous AEP either before or after morphine did not affect
      infarct size. After morphine preconditioning, the beta-EP level decreased in the
      hypothalamic arcuate nucleus and increased significantly in the serum, pituitary
      gland, ventrolateral periaqueductal gray and rostral ventrolateral medulla.
      CONCLUSION: Central but not peripheral beta-EP is involved in morphine remote
      preconditioning and plays a role in the ongoing mediation of cardioprotective
      effects.

PMID- 25971469
TI  - A nation with ambition.

PMID- 25971470
TI  - Polls apart.

PMID- 25971471
TI  - Regulate gene editing in wild animals.

PMID- 25971484
TI  - What the UK election means for science.

PMID- 25971483
TI  - Mappers rush to pinpoint landslide risk in Nepal.

PMID- 25971485
TI  - Rogue antimatter found in clouds.

PMID- 25971486
TI  - Microbiome privacy risk.

PMID- 25971487
TI  - Ebola failures prompt WHO rethink.

PMID- 25971488
TI  - India eases stance on GM crop trials.

PMID- 25971489
TI  - Corrections.

PMID- 25971490
TI  - Science in India.

PMID- 25971491
TI  - India by the numbers.

PMID- 25971492
TI  - India's science test.

PMID- 25971493
TI  - Indian bioscience: The anti-bureaucrat.

PMID- 25971494
TI  - Research management: Priorities for science in India.

PMID- 25971495
TI  - Policy: Rethink India's energy strategy.

PMID- 25971499
TI  - Data analysis: Check the rejects for fame bias too.

PMID- 25971500
TI  - IPCC: social scientists are ready.

PMID- 25971501
TI  - Conservation management: Citizen science is not enough on its own.

PMID- 25971502
TI  - Botany: Plant identification is key to conservation.

PMID- 25971503
TI  - IPCC: calling social scientists of all kinds.

PMID- 25971504
TI  - Astrophysics: The slow death of red galaxies.

PMID- 25971505
TI  - Neuroscience: Internal compass puts flies in their place.

PMID- 25971506
TI  - Microscopy: Quantum control of free electrons.

PMID- 25971507
TI  - Microbiology: Fungus against the wall.

PMID- 25971508
TI  - Molecular biology: Rap and chirp about X inactivation.

PMID- 25971510
TI  - Strangulation as the primary mechanism for shutting down star formation in
      galaxies.
AB  - Local galaxies are broadly divided into two main classes, star-forming (gas-rich)
      and quiescent (passive and gas-poor). The primary mechanism responsible for
      quenching star formation in galaxies and transforming them into quiescent and
      passive systems is still unclear. Sudden removal of gas through outflows or
      stripping is one of the mechanisms often proposed. An alternative mechanism is so
      called "strangulation", in which the supply of cold gas to the galaxy is halted.
      Here we report an analysis of the stellar metallicity (the fraction of elements
      heavier than helium in stellar atmospheres) in local galaxies, from 26,000
      spectra, that clearly reveals that strangulation is the primary mechanism
      responsible for quenching star formation, with a typical timescale of four
      billion years, at least for local galaxies with a stellar mass less than 10(11)
      solar masses. This result is further supported independently by the stellar age
      difference between quiescent and star-forming galaxies, which indicates that
      quiescent galaxies of less than 10(11) solar masses are on average observed four
      billion years after quenching due to strangulation. 

PMID- 25971509
TI  - Neural dynamics for landmark orientation and angular path integration.
AB  - Many animals navigate using a combination of visual landmarks and path
      integration. In mammalian brains, head direction cells integrate these two
      streams of information by representing an animal's heading relative to landmarks,
      yet maintaining their directional tuning in darkness based on self-motion cues.
      Here we use two-photon calcium imaging in head-fixed Drosophila melanogaster
      walking on a ball in a virtual reality arena to demonstrate that landmark-based
      orientation and angular path integration are combined in the population responses
      of neurons whose dendrites tile the ellipsoid body, a toroidal structure in the
      centre of the fly brain. The neural population encodes the fly's azimuth relative
      to its environment, tracking visual landmarks when available and relying on self
      motion cues in darkness. When both visual and self-motion cues are absent, a
      representation of the animal's orientation is maintained in this network through
      persistent activity, a potential substrate for short-term memory. Several
      features of the population dynamics of these neurons and their circular
      anatomical arrangement are suggestive of ring attractors, network structures that
      have been proposed to support the function of navigational brain circuits. 

PMID- 25971511
TI  - Electron pairing without superconductivity.
AB  - Strontium titanate (SrTiO3) is the first and best known superconducting
      semiconductor. It exhibits an extremely low carrier density threshold for
      superconductivity, and possesses a phase diagram similar to that of high
      temperature superconductors--two factors that suggest an unconventional pairing
      mechanism. Despite sustained interest for 50 years, direct experimental insight
      into the nature of electron pairing in SrTiO3 has remained elusive. Here we
      perform transport experiments with nanowire-based single-electron transistors at
      the interface between SrTiO3 and a thin layer of lanthanum aluminate, LaAlO3.
      Electrostatic gating reveals a series of two-electron conductance resonances
      paired electron states--that bifurcate above a critical pairing field Bp of about
      1-4 tesla, an order of magnitude larger than the superconducting critical
      magnetic field. For magnetic fields below Bp, these resonances are insensitive to
      the applied magnetic field; for fields in excess of Bp, the resonances exhibit a
      linear Zeeman-like energy splitting. Electron pairing is stable at temperatures
      as high as 900 millikelvin, well above the superconducting transition temperature
      (about 300 millikelvin). These experiments demonstrate the existence of a robust
      electronic phase in which electrons pair without forming a superconducting state.
      Key experimental signatures are captured by a model involving an attractive
      Hubbard interaction that describes real-space electron pairing as a precursor to
      superconductivity.

PMID- 25971512
TI  - Quantum coherent optical phase modulation in an ultrafast transmission electron
      microscope.
AB  - Coherent manipulation of quantum systems with light is expected to be a
      cornerstone of future information and communication technology, including quantum
      computation and cryptography. The transfer of an optical phase onto a quantum
      wavefunction is a defining aspect of coherent interactions and forms the basis of
      quantum state preparation, synchronization and metrology. Light-phase-modulated
      electron states near atoms and molecules are essential for the techniques of
      attosecond science, including the generation of extreme-ultraviolet pulses and
      orbital tomography. In contrast, the quantum-coherent phase-modulation of
      energetic free-electron beams has not been demonstrated, although it promises
      direct access to ultrafast imaging and spectroscopy with tailored electron pulses
      on the attosecond scale. Here we demonstrate the coherent quantum state
      manipulation of free-electron populations in an electron microscope beam. We
      employ the interaction of ultrashort electron pulses with optical near-fields to
      induce Rabi oscillations in the populations of electron momentum states, observed
      as a function of the optical driving field. Excellent agreement with the scaling
      of an equal-Rabi multilevel quantum ladder is obtained, representing the
      observation of a light-driven 'quantum walk' coherently reshaping electron
      density in momentum space. We note that, after the interaction, the optically
      generated superposition of momentum states evolves into a train of attosecond
      electron pulses. Our results reveal the potential of quantum control for the
      precision structuring of electron densities, with possible applications ranging
      from ultrafast electron spectroscopy and microscopy to accelerator science and
      free-electron lasers. 

PMID- 25971513
TI  - Global carbon export from the terrestrial biosphere controlled by erosion.
AB  - Riverine export of particulate organic carbon (POC) to the ocean affects the
      atmospheric carbon inventory over a broad range of timescales. On geological
      timescales, the balance between sequestration of POC from the terrestrial
      biosphere and oxidation of rock-derived (petrogenic) organic carbon sets the
      magnitude of the atmospheric carbon and oxygen reservoirs. Over shorter
      timescales, variations in the rate of exchange between carbon reservoirs, such as
      soils and marine sediments, also modulate atmospheric carbon dioxide levels. The
      respective fluxes of biospheric and petrogenic organic carbon are poorly
      constrained, however, and mechanisms controlling POC export have remained
      elusive, limiting our ability to predict POC fluxes quantitatively as a result of
      climatic or tectonic changes. Here we estimate biospheric and petrogenic POC
      fluxes for a suite of river systems representative of the natural variability in
      catchment properties. We show that export yields of both biospheric and
      petrogenic POC are positively related to the yield of suspended sediment,
      revealing that POC export is mostly controlled by physical erosion. Using a
      global compilation of gauged suspended sediment flux, we derive separate
      estimates of global biospheric and petrogenic POC fluxes of 157(+74)(-50) and
      43(+61)(-25) megatonnes of carbon per year, respectively. We find that biospheric
      POC export is primarily controlled by the capacity of rivers to mobilize and
      transport POC, and is largely insensitive to the magnitude of terrestrial primary
      production. Globally, physical erosion rates affect the rate of biospheric POC
      burial in marine sediments more strongly than carbon sequestration through
      silicate weathering. We conclude that burial of biospheric POC in marine
      sediments becomes the dominant long-term atmospheric carbon dioxide sink under
      enhanced physical erosion.

PMID- 25971515
TI  - Erratum: Entanglement with negative Wigner function of almost 3,000 atoms
      heralded by one photon.

PMID- 25971514
TI  - Electron cryomicroscopy observation of rotational states in a eukaryotic V
      ATPase.
AB  - Eukaryotic vacuolar H(+)-ATPases (V-ATPases) are rotary enzymes that use energy
      from hydrolysis of ATP to ADP to pump protons across membranes and control the pH
      of many intracellular compartments. ATP hydrolysis in the soluble catalytic
      region of the enzyme is coupled to proton translocation through the membrane
      bound region by rotation of a central rotor subcomplex, with peripheral stalks
      preventing the entire membrane-bound region from turning with the rotor. The
      eukaryotic V-ATPase is the most complex rotary ATPase: it has three peripheral
      stalks, a hetero-oligomeric proton-conducting proteolipid ring, several subunits
      not found in other rotary ATPases, and is regulated by reversible dissociation of
      its catalytic and proton-conducting regions. Studies of ATP synthases, V-ATPases,
      and bacterial/archaeal V/A-ATPases have suggested that flexibility is necessary
      for the catalytic mechanism of rotary ATPases, but the structures of different
      rotational states have never been observed experimentally. Here we use electron
      cryomicroscopy to obtain structures for three rotational states of the V-ATPase
      from the yeast Saccharomyces cerevisiae. The resulting series of structures shows
      ten proteolipid subunits in the c-ring, setting the ATP:H(+) ratio for proton
      pumping by the V-ATPase at 3:10, and reveals long and highly tilted transmembrane
      alpha-helices in the a-subunit that interact with the c-ring. The three different
      maps reveal the conformational changes that occur to couple rotation in the
      symmetry-mismatched soluble catalytic region to the membrane-bound proton
      translocating region. Almost all of the subunits of the enzyme undergo
      conformational changes during the transitions between these three rotational
      states. The structures of these states provide direct evidence that deformation
      during rotation enables the smooth transmission of power through rotary ATPases. 

PMID- 25971517
TI  - Healthy fats for healthy nutrition. An educational approach in the workplace to
      regulate food choices and improve prevention of non-communicable diseases.
AB  - INTRODUCTION: An educational activity, aimed at highlighting the benefits of
      Mediterranean Diet, compared to less healthy eating patterns, can encourage the
      adoption and maintenance of a mindful approach to food choice. This is especially
      important when a progressive shift towards a non-Mediterranean dietary pattern
      can be observed, even in Mediterranean countries. AIM: To test a protocol aimed
      at increasing knowledge and motivation to embrace healthy eating habits and,
      engendering conscientious food choices, improve the prevention of non
      communicable diseases. METHODS: Employees were involved in educational activities
      focusing on a healthy Mediterranean diet and on the role played by extra-virgin
      olive oil, one of its key components. Food questionnaires were completed both
      before and after the educational and information activities, in order to assess
      changes in personal knowledge of and attitudes towards fat consumption. RESULTS:
      Answers on dietary guidelines and fat properties were more accurate after the
      seminars. The results showed increased understanding of the properties of extra
      virgin olive oil versus seed oil and a stronger tendency towards healthy food
      choices. CONCLUSIONS: Implementing preventive information and training strategies
      and tools in the workplace, can motivate a more mindful approach to food choice
      with the long-term goal of contribute to reducing non-communicable diseases.

PMID- 25971518
TI  - Toxic elements in groundwater of Lagos and Ogun States, Southwest, Nigeria and
      their human health risk assessment.
AB  - A good quality drinking water is essential for human survival. However, a large
      percentage of the populations in most developing countries (Nigeria inclusive) do
      not have access to potable water. This study was therefore conducted to assess
      the extent of risk arising from consumption of toxic elements in groundwater
      samples collected from Lagos and Ogun States, Southwest, Nigeria. Twelve toxic
      elements concentrations (As, Mn, Cd, Cr, Pb, Ni, Al, Ti, V, Hg, Li, and Sn) were
      determined from 170 groundwater samples using inductively coupled plasma-mass
      spectrometry, and the physicochemical parameters were determined using standard
      methods. The pH results revealed that most of the water samples were slightly
      acidic. Of the twelve toxic elements, only Mn, Cd, Pb, Ni, and Al have
      concentrations higher than the WHO recommended limit in drinking water. The
      average dose of Mn and Al consumed daily from groundwater by an adult in Lagos
      state is 3.4 and 23.2 (MUg/kg body weight), respectively. Similarly, an adult in
      Ogun State consumed an average daily dose of 6.09 and 25 (MUg/kg body weight) Mn
      and Al, respectively. A greater threat was posed to children and infants. The
      order for risk of cancer in groundwater from Lagos State was Pb > Cr > As > Cd
      while the order in Ogun State groundwater was Cr > Cd > As > Pb. The relative
      high concentrations of Mn, Al, and Pb obtained in this study can be attributed to
      industrial and anthropogenic activities in the study area. Treatment of
      groundwater before consumption is recommended to avoid possible adverse
      cumulative effect. Improved waste disposal methods and regular monitoring of
      toxic elements in groundwater of the study area should be adopted to safeguard
      human health.

PMID- 25971519
TI  - Multicriteria decision analysis for monitoring ecosystem service function of the
      Three-River Headwaters region of the Qinghai-Tibet Plateau, China.
AB  - The Three-River Headwaters (TRH) region in the Qinghai-Tibet Plateau, China, is
      of key importance to the ecological security of China and Southeast Asia and
      contains some of the most sensitive and fragile ecosystems. Monitoring and
      evaluating the ecosystem service function and its changes in the TRH region could
      support decision-making for regional ecological protection and restoration
      programs. Referencing the concept of ecosystem service and the Millennium
      Ecosystem Assessment (MA) framework, this study built a system of indicators for
      monitoring and evaluating the ecosystem service function. Thus, combining a
      multicriteria decision analysis (MCDA) and weighted linear combination (WLC) with
      analytic hierarchy process (AHP), we applied the ecosystem service function index
      (ESFI) based on remote sensing data at 1-km spatial resolution to
      spatiotemporally monitor the changes during the period 2005-2010. The study
      results indicated that ESFI had a good performance for monitoring the ecosystem
      service function and showed an improving trend in the TRH region over the past 5
      years. Ecosystem environment recovery not only reflected the changing trend of
      warm and wet climate but was also a response of the ecological protection project
      of the Key Ecological Function Zone in the TRH region.

PMID- 25971520
TI  - Detection of persistent OCPs and PCBs congeners in the near-shore coastal waters
      of Alexandria, Egypt.
AB  - The residues of 19 EPA-organochlorine pesticides (OCPs) and polychlorinated
      biphenyls (PCBs) were determined in water samples collected from the near-shore
      surface water of Alexandria coast, Egypt, using gas chomatograph-electron capture
      detector (GC-ECD) and gas chromatograph-mass spectometer (GC-MS). Higher
      concentrations of hexachlorocyclohexane (HCH)s, TC, and 2,2-bis (p-chlorophenyl)
      1,1,1-trichloroethane (DDT)s with 1.36, 0.556, and 36.97 ngl(-1) were recorded,
      respectively, with a maximum of 165.46 ngl(-1) of PCBs during June 2014, which
      was clearly affected by higher sewage activities during summer season. Among DDTs
      metabolites, p,p-DDT was the most dominant with a maximum of 36.31 ngl(-1)
      recorded at El-Montazah station during June 2014.

PMID- 25971521
TI  - Development of the Trophic Water Quality Index (TWQI) for subtropical temperate
      Brazilian lotic systems.
AB  - This research aimed at developing the Trophic Water Quality Index (TWQI) for
      subtropical temperate Brazilian lotic systems based on a review of the indicative
      values of diatom species obtained using multivariate analysis techniques and
      considering the environmental gradient defined by a series of measured physical,
      chemical, and microbiological variables. Sampling was conducted from 2005 to 2009
      in the Pardo River Hydrographic Basin, Rio Grande do Sul (RS), Brazil, and in the
      Andreas Stream Hydrographic Basin, RS, from 2012 to 2013. A total of 140
      biological samples and 211 abiotic samples were collected. Data were analyzed by
      cluster analysis based on the Ward method and canonical correspondence analysis
      (CCA). The results indicated that total phosphate, turbidity, ammonia nitrogen,
      electrical conductivity, dissolved oxygen, and thermotolerant coliforms showed a
      significant correlation with the sample ordination made by CCA, in relation to a
      gradient of eutrophication. Eutrophication was operationally defined in a broad
      sense, including the problem of organic pollution and eutrophication of the
      water. The determination of the different tolerance degrees to eutrophication of
      the diatom taxa was used to assign trophic values of 1, 2.5, and 4 to species,
      corresponding to levels of low, medium, and high tolerance, respectively. By
      using the trophic values obtained for each diatom species, the TWQI constituted a
      new technological tool for environmental monitoring studies and showed a
      consistent, robust, and objective database for water quality assessment in
      subtropical temperate Brazilian lotic systems. 

PMID- 25971523
TI  - Factors associated with passing the European Board of Paediatric Surgery Exam.
AB  - PURPOSE: The European Board of Paediatric Surgery (EBPS) includes a written Part
      1 and an oral/practical Part 2 component. The goal of this study was to describe
      the EBPS examination candidate pool, and to determine factors associated with
      successfully passing the examination. METHODS: A database including all
      registered candidates for the EBPS exams since 2005 was constructed. Queried
      information included demographics, training location, language proficiency, and
      written/oral scores. Logistic regression analysis was performed to elucidate
      variables predictive of examination success. RESULTS: Until 2013, a total of 370
      candidates registered for the part 1 examination and 147 successfully passed part
      2. Pass rates for part 1 were 68, 65, 20, and 0 % on first, second, third, and
      forth attempts, respectively. Pass rates for part 2 were 79 % for both first and
      second attempts. Training in a single country was associated with passing Part 1
      (p = 0.048), while having completed at least some training in an English-speaking
      country increased the chance of passing Part 2 (p < 0.01). CONCLUSION: The pool
      of EBPS examination candidates is highly diverse and international. First- and
      second-attempt pass rates are similar for both parts. Candidates who completed
      all their training in non-English-speaking countries may wish to consider
      additional English language practice to increase their chances of success.

PMID- 25971522
TI  - Assessment of exposure to soils contaminated with lead, cadmium, and arsenic near
      a zinc smelter, Cassiopee Study, France, 2008.
AB  - After 150 years of industrial activity, significant pollution of surface soils in
      private gardens and locally produced vegetables with lead, cadmium, and arsenic
      has recently been observed in Viviez (Southern France). A public health
      intervention was conducted in 2008 to identify individual health risks of Viviez
      inhabitants and to analyze their environmental exposure to these pollutants.
      Children and pregnant women in Viviez were screened for lead poisoning. Urinary
      cadmium testing was proposed to all inhabitants. Those with urinary cadmium
      levels over 1 MUg/g creatinine were then tested for kidney damage. Urinary
      cadmium and arsenic levels were compared between participants with non
      occupational exposure from Viviez and Montbazens, a nearby town not exposed to
      these two pollutants, in order to identify environmental factors contributing to
      impregnation. No case of lead poisoning was detected in Viviez, but 23 % of
      adults had urinary cadmium over 1 MUg/g creatinine, 14 % of whom having markers
      of kidney damage. Viviez adults had higher levels of urinary cadmium, and to a
      lesser extent, higher levels of urinary arsenic than those from Montbazens.
      Consumption of local produce (vegetables and animals) and length of residence in
      Viviez were associated with higher urinary cadmium levels, independently of known
      confounding factors, suggesting persisting environmental exposure to contaminated
      soil. To conclude, health risks related to cadmium exposure were identified in
      the Viviez population living on contaminated soils. Lead and arsenic exposure did
      not pose health concerns. Interventions were proposed to reduce exposure and
      limit health consequences.

PMID- 25971524
TI  - Prophylactic Intra-Aortic Balloon Pump Before Ventricular Assist Device
      Implantation Reduces Perioperative Medical Expenses and Improves Postoperative
      Clinical Course in INTERMACS Profile 2 Patients.
AB  - BACKGROUND: Although intra-aortic balloon pump (IABP) is sometimes used before
      cardiac surgery to achieve better outcome in high-risk patients, the clinical
      impact of prophylactic IABP support before left ventricular assist device (LVAD)
      implantation in patients with worsening hemodynamics was unknown. METHODS AND
      RESULTS: We enrolled 22 patients with worsening hemodynamics who had received
      IABP support before LVAD (IABP group), and also enrolled 22 patients receiving
      neither IABP nor extracorporeal membrane oxygenation before LVAD, who were
      selected on propensity score matching (non-IABP group). Although both groups had
      similar preoperative background, the IABP group had shorter postoperative
      intensive care unit (ICU) stay, and more improved hemodynamics (P<0.05 for all).
      Serum total bilirubin and creatinine decreased significantly in the IABP group
      compared with the non-IABP group during 1 month after LVAD implantation (P<0.05
      for both). Medical expenses during perioperative ICU stay were significantly
      lower in the IABP group compared with the non-IABP group, even including the cost
      of preoperative IABP support (P<0.05). CONCLUSIONS: Prophylactic IABP support in
      heart failure patients with worsening hemodynamics improves post-LVAD clinical
      course and reduces perioperative medical expenses.

PMID- 25971525
TI  - Validation of Risk Scoring System Excluding Female Sex From CHA2DS2-VASc in
      Japanese Patients With Nonvalvular Atrial Fibrillation - Subanalysis of the J
      RHYTHM Registry.
AB  - BACKGROUND: Because the current Japanese guideline recommends CHADS2 score-based
      risk stratification in nonvalvular atrial fibrillation (NVAF) patients and does
      not list female sex as a risk for thromboembolic events, we designed the present
      study to compare the CHA2DS2-VASc and CHA2DS2-VA scores in the J-RHYTHM Registry.
      METHODS AND RESULTS: We prospectively assessed the incidence of thromboembolic
      events for 2 years in 997 NVAF patients without warfarin treatment (age 68+/-12
      years, 294 females). The predictive value of the CHA2DS2-VASc and CHA2DS2-VA
      scores for thromboembolic events was evaluated by c-statistic difference and net
      reclassification improvement (NRI). Thromboembolic events occurred in 7/294
      females (1.2%/year) and 23/703 males (1.6%/year) (odds ratio 0.72 for female to
      male, 95% confidence interval (CI) 0.28-1.62, P=0.44). No sex difference was
      found in patient groups stratified by CHA2DS2-VASc and CHA2DS2-VA scores. There
      were significant c-statistic difference (0.029, Z=2.3, P=0.02) and NRI (0.11, 95%
      CI 0.01-0.20, P=0.02), with the CHA2DS2-VA score being superior to the CHA2DS2
      VASc score. In patients with CHA2DS2-VASc scores 0 and 1 (n=374), there were
      markedly significant c-statistic difference (0.053, Z=6.6, P<0.0001) and NRI
      (0.11, 95% CI 0.07-0.14, P<0.0001), again supporting superiority of CHA2DS2-VA to
      CHA2DS2-VASc score. CONCLUSIONS: In Japanese NVAF patients, the CHA2DS2-VA score,
      a risk scoring system excluding female sex from CHA2DS2-VASc, may be more useful
      in risk stratification for thromboembolic events than CHA2DS2-VASc score,
      especially in identifying truly low-risk patients.

PMID- 25971526
TI  - Bacterial Contamination During Pacemaker Implantation Is Common and Does Not
      Always Result in Infection.
AB  - BACKGROUND: Bacterial cultures of cardiovascular implantable electronic devices
      removed from patients without clinical infection are often positive, and the
      cultured bacteria are different from those at the time of clinical infection.
      This discrepancy has not been adequately explained. We hypothesized that the
      cause is bacterial contamination at operation and compared the results of
      bacterial cultures between patients with de novo pacemaker implantation and those
      with pacemaker replacement. METHODS AND RESULTS: We prospectively enrolled
      consecutive 100 patients who underwent cardiac pacemaker implantation (49 de novo
      implantations, 51 replacements). We took swab cultures from inside the generator
      pocket (1) immediately after the creation of new pocket or removal of old
      generator, (2) after connection of leads to new generator, and (3) after pocket
      lavage. Swab cultures were positive in 272 (45%) of 600 samples. The majority of
      the cultured bacteria were Propionibacterium species. No statistical difference
      was detected between de novo implantations and replacements in the positive ratio
      of swab cultures. The positive ratio was not correlated with the number of
      previous device replacements. CONCLUSIONS: The positive ratio of swab cultures
      was not different between new implantations and replacements, suggesting that a
      positive culture merely indicates contamination of bacteria during operation
      rather than colonization.

PMID- 25971528
TI  - Cationic gold clusters ligated with differently substituted phosphines: effect of
      substitution on ligand reactivity and binding.
AB  - We present a systematic study of the effect of the number of methyl (Me) and
      cyclohexyl (Cy) functional groups in monodentate phosphine ligands on the
      solution-phase synthesis of ligated sub-nanometer gold clusters and their gas
      phase fragmentation pathways. Small mixed ligand cationic gold clusters were
      synthesized using reactions between pre-formed triphenylphosphine ligated (PPh3)
      gold clusters and monodentate Me- and Cy-substituted phosphine ligands in
      solution and characterized using electrospray ionization mass spectrometry (ESI
      MS) and collision-induced dissociation (CID) experiments. Under the same
      experimental conditions, larger gold-PPh3 clusters undergo efficient exchange of
      unsubstituted PPh3 ligands for singly Me- and Cy-substituted PPh2Me and PPh2Cy
      ligands. The efficiency of reaction decreases with an increasing number of Me or
      Cy groups in the substituted phosphine ligands. CID experiments performed for a
      series of mixed-ligand gold clusters indicate that loss of a neutral Me
      substituted ligand is preferred over loss of a neutral PPh3 ligand while the
      opposite trend is observed for Cy-substituted ligands. The branching ratio of the
      competing ligand loss channels is strongly correlated with the electron donating
      ability of the phosphorous lone pair as determined by the relative proton
      affinity of the ligand. The results indicate that the relative ligand binding
      energies increase in the order PMe3 < PPhMe2 < PPh2Me < PPh3 < PPh2Cy < PPhCy2 <
      PCy3. Furthermore, the difference in relative ligand binding energies increases
      with the number of substituted PPh(3-m)Me(m) or PPh(3-m)Cy(m) ligands (L) on each
      cluster. This study provides the first experimental determination of the relative
      binding energies of ligated gold clusters containing differently substituted
      monophosphine ligands, which are important to controlling their synthesis and
      reactivity in solution. The results also indicate that ligand substitution is an
      important parameter that must be considered in theoretical modeling of these
      complex systems.

PMID- 25971527
TI  - miRNA-202 in bone marrow stromal cells affects the growth and adhesion of
      multiple myeloma cells by regulating B cell-activating factor.
AB  - Bone marrow stromal cells (BMSCs) up-regulate B cell-activating factor (BAFF) in
      multiple myeloma. Increasing experimental evidence has shown that microRNAs play
      a causal role in hematology tumorigenesis. In this study, we characterized the
      role of miR-202 in regulating the expression of BAFF in BMSCs. It was found that
      expressions of BAFF mRNA and protein were increased in BMSCs treated with miR-202
      inhibitor. The growth rate of miR-202 mimics transfection cells was significantly
      lower than that of non-transfected cells. The expression of Bcl-2 protein was
      down-regulated, and Bax protein was up-regulated after miR-202 mimics
      transfection. Over-expression of miR-202 in BMSCs rendered MM cells more
      sensitive to bortezomib. More significantly, the regulatory effect of miR-202
      could inhibit the activation of NF-kappaB pathway in BMSCs. These results suggest
      that miR-202 functions as a modulator that can negatively regulate BAFF by
      inhibiting MM cell survival, growth, and adhesion in the bone marrow
      microenvironment. 

PMID- 25971529
TI  - Mild arylboronic acid catalyzed selective [4 + 3] cycloadditions: access to
      cyclohepta[b]benzofurans and cyclohepta[b]indoles.
AB  - The first example of arylboronic acid catalyzed [4 + 3] cycloaddition reaction is
      reported. 3,5-Bis-(trifluoromethyl) phenylboronic acid is shown to be the best
      catalyst in this reaction. The method has also enabled the preparation of
      cyclohepta[b]benzofurans and cyclohepta[b]indoles in excellent yields. 

PMID- 25971530
TI  - Individual and societal consequences of hypoglycemia: A cross-sectional survey.
AB  - BACKGROUND: Hypoglycemia and fear of hypoglycemia threaten individuals' ability
      to work and drive. We studied the effect of hypoglycemia on the individual and
      society, with a focus on possible implications of new European union legislation
      on patients' continued ability to drive. METHODS: A cross-sectional survey of
      Danish Diabetes Association members was conducted to investigate individual and
      societal consequences of hypoglycemia. RESULTS: A total of 3117/9951 individuals
      with type 1 diabetes (T1DM) (32.2%) or type 2 diabetes (T2DM) (67.8%) completed
      the survey. The calculated incidence rates of self-reported severe and mild
      hypoglycemia were 2.9, 0.6 and 0.1 events per patient year (ppy) in patients with
      T1DM, insulin using T2DM and non-insulin using T2DM, respectively; and incidence
      rates of self-reported mild hypoglycemia were 99.0, 23.2 and 10.9 events ppy,
      respectively. Self-care strategies to avoid hypoglycemia include maintaining
      higher blood glucose levels (45.7%) and reducing physical activity (15.7%). Few
      people take sick leave as a result of hypoglycemia, but prolonged mental recovery
      >=4 h following an episode of mild or severe hypoglycemia was reported by 8.7 and
      31.0%, respectively. 26.5% of patients holding a valid driving license reported
      having ever had at least one episode of severe hypoglycemia. Patients considering
      underreporting of hypoglycemia to maintain their driving license were more likely
      to have experienced severe hypoglycemia (odds ratio [OR]: 3.03; 95% CI: 2.42
      3.79; p < 0.0001). CONCLUSION: A high proportion of insulin-treated patients
      experience hypoglycemia resulting in fear of hypoglycemia and changes in self
      care behavior that may compromise glycemic control. Many patients with a history
      of severe hypoglycemia consider underreporting hypoglycemic events through
      concern over retaining their driving license.

PMID- 25971531
TI  - Childhood central nervous system tumours: Incidence and time trends in 13
      Southern and Eastern European cancer registries.
AB  - AIM: Following completion of the first 5-year nationwide childhood (0-14 years)
      registration in Greece, central nervous system (CNS) tumour incidence rates are
      compared with those of 12 registries operating in 10 Southern-Eastern European
      countries. METHODS: All CNS tumours, as defined by the International
      Classification of Childhood Cancer (ICCC-3) and registered in any period between
      1983 and 2014 were collected from the collaborating cancer registries. Data were
      evaluated using standard International Agency for Research on Cancer (IARC)
      criteria. Crude and age-adjusted incidence rates (AIR) by age/gender/diagnostic
      subgroup were calculated, whereas time trends were assessed through Poisson and
      Joinpoint regression models. RESULTS: 6062 CNS tumours were retrieved with non
      malignant CNS tumours recorded in eight registries; therefore, the analyses were
      performed on 5191 malignant tumours. Proportion of death certificate only cases
      was low and morphologic verification overall high; yet five registries presented
      >10% unspecified neoplasms. The male/female ratio was 1.3 and incidence decreased
      gradually with age, apart from Turkey and Ukraine. Overall AIR for malignant
      tumours was 23/10(6) children, with the highest rates noted in Croatia and
      Serbia. A statistically significant AIR increase was noted in Bulgaria, whereas
      significant decreases were noted in Belarus, Croatia, Cyprus and Serbia. Although
      astrocytomas were overall the most common subgroup (30%) followed by embryonal
      tumours (26%), the latter was the predominant subgroup in six registries.
      CONCLUSION: Childhood cancer registration is expanding in Southern-Eastern
      Europe. The heterogeneity in registration practices and incidence patterns of CNS
      tumours necessitates further investigation aiming to provide clues in aetiology
      and direct investments into surveillance and early tumour detection.

PMID- 25971532
TI  - Decline in CA19-9 during chemotherapy predicts survival in four independent
      cohorts of patients with inoperable bile duct cancer.
AB  - BACKGROUND: Carbohydrate associated antigen (CA19-9) has been approved by the FDA
      as a biomarker for monitoring treatment effect in pancreatic cancer. However, the
      value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct
      cancer is unclear. The aim of this study was to determine if a decline in CA19-9
      (CA19-9 response) during chemotherapy is predictive of survival in patients with
      inoperable bile duct cancer. METHODS: Consecutive patients with inoperable bile
      duct cancer treated at a University Hospital were retrospectively included in an
      investigational cohort (n = 212). Three validation cohorts were established
      including patients 1) participating in phase I/II trials at a Danish Hospital (n
      = 71), 2) identified retrospectively in a Canadian cohort (n = 196) and 3)
      randomized in the ABC-02 trial (n = 410). Patients with a baseline CA19-9 and at
      least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were
      included. Multivariate Cox regression analyses were performed. RESULTS: Patients
      meeting the criteria to be included were 54 in the investigational cohort and 34,
      68 and 148 in the three validation sets, respectively. Multivariate analysis
      included radiological response, performance status, bilirubin, gender, site of
      cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of
      0.60 (95%CI: 0.44-0.80, p = 0.0005) for death in CA19-9 responders was reached in
      the investigational cohort. The predictive value of CA 19-9 response was
      confirmed in all three validation cohorts. CONCLUSIONS: CA19-9 response is a
      robust predictor of survival in patients with inoperable bile duct cancer in four
      independent data sets.

PMID- 25971533
TI  - Long-Term Comparison of Porous Versus Hydroxyapatite Coated Sleeve of a Modular
      Cementless Femoral Stem (SROM) in Primary Total Hip Arthroplasty.
AB  - Hydroxyapatite (HA) is commonly used on femoral stems to assist in osseous
      integration but there is limited evidence of the benefit it provides. We report a
      prospective comparison of 117 and 102 patients receiving either porous or HA
      coated sleeves respectively. Patients were evaluated at mean of 12.5 years in the
      porous and 13.7 years in the HA groups. The mean Harris Hip Score was 94.7 and
      94.5 in the porous and HA groups respectively. One porous and 2 HA stems required
      revision. This study demonstrates that there is no long-term advantage to using
      an HA coating on the sleeve of this modular stem and confirms excellent long-term
      results for the SROM stem in a primary arthroplasty setting. LEVEL OF EVIDENCE:
      II (prospective cohort study).

PMID- 25971534
TI  - Fluctuation of Cup Orientation During Press-Fit Insertion: A Possible Cause of
      Malpositioning.
AB  - We evaluated real-time angular changes during press-fit cup insertion in 70 total
      hip arthroplasties. Inclination and anteversion cup angles on navigation system
      were recorded after each procedure of five hammer blows during cup insertion, and
      maximum deviated inclination (MDI) and anteversion (MDA) angles until the cup was
      fully seated were measured. We found 1 (1%) and 29 (41%) hips with increases and
      decreases in MDI of 5 degrees  or more, and 13 (19%) and 6 (8%) hips with
      increases and decreases in MDA of 5 degrees  or more, respectively. The MDI in
      men was significantly lower and the MDA for left-side surgery was significantly
      higher. Surgeons should pay attention to fluctuation in angular changes during
      cup insertion and may consider countermeasures to minimize cup malpositioning. 

PMID- 25971535
TI  - Oxidation of Second Generation Sequentially Irradiated and Annealed Highly Cross
      Linked X3TM Polyethylene Tibial Bearings.
AB  - Since the first use of ultra-high-molecular-weight polyethylene as a bearing
      material, research and development efforts have sought to improve wear
      resistance, increase longevity and lessen the potential for debris mediated
      adverse tissue responses. A series of second generation sequentially cross-linked
      and annealed tibial bearings were analysed after several bearings sent for
      routine retrieval analysis showed oxidative degradation including subsurface
      whitening, cracking and gross material loss. Evaluation incorporated visual and
      white banding assessment, mechanical testing and spectroscopy analysis. Whilst
      visual observation and white banding assessment confirmed oxidative changes, a
      decrease in mechanical properties and increasing ketone oxidation index as a
      function of time in vivo suggest time dependent oxidative degradation. Clinically
      relevant degradation of the sequentially cross-linked and annealed tibial
      bearings was observed. 

PMID- 25971537
TI  - Activity of selected coagulation factors in overt and subclinical
      hypercortisolism.
AB  - It is universally acknowledged that glucocorticoids are hormones that exert a
      significant effect on hemostasis. The aim of this study was to analyze the
      activities of coagulation factors VIII, von Willebrand (vW), IX, X, and XI, in
      patients with overt and subclinical hypercortisolism, as well as to examine
      possible associations between activities of these factors and the degree of
      hypercortisolism. Thirty endogenous hypercortisolemic patients were included in
      the study. Twelve of them were diagnosed with overt Cushing's syndrome (OCS), and
      eighteen with subclinical Cushing's syndrome (SCS). Healthy, age- and sex-matched
      volunteers comprised the control group. Activities of coagulation factors VIII,
      IX, X, and XI were examined using a coagulometric method, and von Willebrand
      factor (vWF) using an immunoturbidimetric method. Mean activities of examined
      coagulation factors were significantly higher in OCS patients in comparison to
      healthy controls. SCS patients had significantly higher mean vWF activities
      versus controls; and a clear trend toward higher mean activities of other factors
      in SCS patients versus controls was recorded (but no significant differences).
      Furthermore, statistically significant positive correlations were found between
      activities of factor IX and: morning serum cortisol concentrations, 24-hour
      urinary cortisol excretion values, cortisol concentrations in the overnight
      suppression test with 1 mg of dexamethasone. Activities of factors X and XI
      positively correlated with cortisol levels in the overnight suppression test. In
      endogenous hypercortisolemic patients the coagulation pathway is hyperactivated
      as indicated by increased activities of coagulation factors. These disorders are
      evident among patients with overt hypercortisolism. 

PMID- 25971536
TI  - Ion Trapping, Storage, and Ejection in Structures for Lossless Ion Manipulations.
AB  - A new Structures for Lossless Ion Manipulations (SLIM) module, having electrode
      arrays patterned on a pair of parallel printed circuit boards (PCB), was
      constructed and utilized to investigate capabilities for ion trapping at a
      pressure of 4 Torr. Positive ions were confined by application of RF voltages to
      a series of inner rung electrodes with alternating phase on adjacent electrodes,
      in conjunction with positive DC potentials on surrounding guard electrodes on
      each PCB. An axial DC field was also introduced by stepwise varying the DC
      potentials applied to the inner rung electrodes to control the ion transport and
      accumulation inside the ion trapping region. We show that ions can be trapped and
      accumulated with up to 100% efficiency, stored for at least 5 h with no
      significant losses, and then could be rapidly ejected from the SLIM trap. The
      present results provide a foundation for the development of much more complex
      SLIM devices that facilitate extended ion manipulations. 

PMID- 25971538
TI  - Ultrasonographic appearance of focal Hashimoto's thyroiditis: A single
      institution experience.
AB  - The purpose of this study was to determine the ultrasonographic (US) appearance
      of focal Hashimoto's thyroiditis (FHT). Thirty-seven FHT patients and 60
      consecutive patients with 60 papillary thyroid carcinomas (PTC) that were
      confirmed by cytology or histopathology between January 2011 and December 2013
      were analyzed. Using the results of color Doppler imaging, US findings were
      retrospectively reviewed. Inter-group differences in size, internal content,
      echogenicity, echo texture, shape, boundary, margin, calcifications, fine
      echogenic septa, and blood flow were statistically assessed. The US appearances
      of the FHTs examined were: solid (100%), hypoechoic (97%), heterogeneous (68%),
      ovoid-to-round shape (73%), well-defined boundary (95%), smooth margin (89%), and
      hypervascular (46%). Ovoid-to-round shape, well-defined boundary, fine echogenic
      septa, and hypervascularity were significantly more prevalent for FHTs than for
      PTCs (p < 0.05). Ovoid-to-round shape and fine echogenic septa have a higher
      specificity and positive predictive value. FHTs show a spectrum of US
      appearances, making FHT diagnosis cumbersome. Fine echogenic septa are highly
      specific for FHT. Ovoid-to-round shape, well-defined boundary and
      hypervascularity may possibly be associated with FHT. 

PMID- 25971539
TI  - Chronobiology of ethanol: animal models.
AB  - Clinical and epidemiological observations have revealed that alcohol abuse and
      alcoholism are associated with widespread disruptions in sleep and other
      circadian biological rhythms. As with other psychiatric disorders, animal models
      have been very useful in efforts to better understand the cause and effect
      relationships underlying the largely correlative human data. This review
      summarizes the experimental findings indicating bidirectional interactions
      between alcohol (ethanol) consumption and the circadian timing system,
      emphasizing behavioral studies conducted in the author's laboratory. Together
      with convergent evidence from multiple laboratories, the work summarized here
      establishes that ethanol intake (or administration) alters fundamental properties
      of the underlying circadian pacemaker. In turn, circadian disruption induced by
      either environmental or genetic manipulations can alter voluntary ethanol intake.
      These reciprocal interactions may create a vicious cycle that contributes to the
      downward spiral of alcohol and drug addiction. In the future, such studies may
      lead to the development of chronobiologically based interventions to prevent
      relapse and effectively mitigate some of the societal burden associated with such
      disorders.

PMID- 25971540
TI  - Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a
      melanoma patients: results of a phase II study.
AB  - The intratumoral injection of cytokines, in particular IL2, has shown promise for
      cutaneous melanoma patients with unresectable disease or continuous recurrence
      despite surgery. We recently reported that the intralesional injection of L19
      IL2, an immunocytokine combining IL2 and the human monoclonal antibody fragment
      L19, resulted in efficient regional control of disease progression, increased
      time to distant metastasis and evidence of effect on circulating immune cell
      populations. We have also shown in preclinical models of cancer a remarkable
      synergistic effect of the combination of L19-IL2 with L19-TNF, a second clinical
      stage immunocytokine, based on the same L19 antibody fused to TNF. Here, we
      describe the results of a phase II clinical trial based on the intralesional
      administration of L19-IL2 and L19-TNF in patients with stage IIIC and IVM1a
      metastatic melanoma, who were not candidate to surgery. In 20 efficacy-evaluable
      patients, 32 melanoma lesions exhibited complete responses upon intralesional
      administration of the two products, with mild side effects mainly limited to
      injection site reactions. Importantly, we observed complete responses in 7/13
      (53.8 %) non-injected lesions (4 cutaneous, 3 lymph nodes), indicating a systemic
      activity of the intralesional immunostimulatory treatment. The intralesional
      administration of L19-IL2 and L19-TNF represents a simple and effective method
      for the local control of inoperable melanoma lesions, with a potential to
      eradicate them or make them suitable for a facile surgical removal of the
      residual mass.

PMID- 25971541
TI  - Cytokine production in patients with papillary thyroid cancer and associated
      autoimmune Hashimoto thyroiditis.
AB  - Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while
      papillary thyroid cancer (PTC) is one of the most common endocrine malignancies.
      A few patients with HT also develop PTC. The aim of this study was to analyze
      cytokine profiles in patients with PTC accompanied with autoimmune HT in
      comparison with those in patients with PTC alone or HT alone and healthy
      subjects. Cytokine levels were determined in supernatants obtained from
      phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The
      concentrations of selected cytokines: Th1-interferon gamma (IFN-gamma); Th2
      interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10
      (IL-10) and interleukin 13 (IL-13); Th9-interleukin 9 (IL-9); and Th17
      interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems
      for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced
      significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-gamma than
      PTC patients without HT. In conclusion, autoimmune HT affects the cytokine
      profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of
      cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT
      indicate a marked shift toward Th2 immunity.

PMID- 25971542
TI  - Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and
      immune recovery after hematopoietic stem cell transplantation.
AB  - Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma
      cells in the bone marrow and causes several immune alterations in patients.
      Thymosin alpha1 (Talpha1) is a thymic peptide that has been associated with
      immuno-stimulating properties. In addition, this peptide exerts anti-tumor
      effects in several cancer types. Beneficial effects of Talpha1 administration
      have also been shown on immune reconstitution after hematopoietic stem cell
      transplantation (HSCT), a current treatment modality in hematological
      malignancies including MM. In this study, we observed a slight reduction in the
      proliferation of murine and human MM cell lines in the presence of Talpha1 in
      vitro. However, using two immunocompetent murine MM models (5TGM1 and
      MOPC315.BM), we did not observe any impact of Talpha1 administration on MM
      development in vivo. Furthermore, no beneficial effects of Talpha1 treatment were
      observed on lymphocyte immune reconstitution after transfusion of human
      hematopoietic stem cells into immunodeficient mice. In conclusion, despite direct
      effects of Talpha1 on human MM cell line proliferation in vitro, Talpha1 did not
      exert anti-myeloma effects in vivo in the two murine models tested. Moreover,
      Talpha1 failed to improve immune recovery in a xenogeneic HSCT model.

PMID- 25971545
TI  - BRAF p.V600E immunohistochemistry in challenging samples: about false-positive
      and false-negative results--reply.

PMID- 25971544
TI  - A DT-diaphorase responsive theranostic prodrug for diagnosis, drug release
      monitoring and therapy.
AB  - A DT-diaphorase-activatable theranostic prodrug, which contains camptothecin, a
      self-immolative linker and a trigger group, has been developed for the detection
      of DT-diaphorase, tracking of drug release and selectively killing cancer cells
      over-expressed with DT-diaphorase. This strategy may offer a new approach for the
      development of enzyme-catalyzed theranostic anticancer therapeutics. 

PMID- 25971543
TI  - Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased
      brain damage and reduced recovery from ischemic stroke in mice.
AB  - Oxidative DNA damage is mainly repaired by base excision repair (BER).
      Previously, our laboratory showed that mice lacking the BER glycosylases 8
      oxoguanine glycosylase 1 (Ogg1) or nei endonuclease VIII-like 1 (Neil1) recover
      more poorly from focal ischemic stroke than wild-type mice. Here, a mouse model
      was used to investigate whether loss of 1 of the 2 alleles of X-ray repair cross
      complementing protein 1 (Xrcc1), which encodes a nonenzymatic scaffold protein
      required for BER, alters recovery from stroke. Ischemia and reperfusion caused
      higher brain damage and lower functional recovery in Xrcc1(+/-) mice than in wild
      type mice. Additionally, a greater percentage of Xrcc1(+/-) mice died as a result
      of the stroke. Brain samples from human individuals who died of stroke and
      individuals who died of non-neurological causes were assayed for various steps of
      BER. Significant losses of thymine glycol incision, abasic endonuclease incision,
      and single nucleotide incorporation activities were identified, as well as lower
      expression of XRCC1 and NEIL1 proteins in stroke brains compared with controls.
      Together, these results suggest that impaired BER is a risk factor in ischemic
      brain injury and contributes to its recovery.

PMID- 25971546
TI  - Napsin A is frequently expressed in clear cell carcinoma of the ovary and
      endometrium.
AB  - Napsin A is a reliable marker for pulmonary adenocarcinoma and is expressed in a
      subset of ovarian clear cell carcinomas (O-CCCs), endometrial (EM) CCCs, and
      endometrioid carcinomas (EC). We investigated napsin A levels in O-CCC and EM-CCC
      and compared these with levels in other nonmucinous ovarian carcinomas and EM-EC,
      respectively. Napsin A, thyroid transcription factor (TTF)-1, paired box (PAX) 8,
      and cancer antigen (CA) 125 expression was evaluated in 111 ovarian and uterine
      carcinoma cases (22 O-CCC, 15 EM-CCC, 13 ovarian EC (O-EC), 39 high-grade serous
      carcinoma [HGSC], and 22 EM-EC) using immunohistochemistry. Napsin A
      immunoreactivity was observed in 21 (95.5%) of 22 O-CCC and 10 (66.7%) of 15 EM
      CCC cases but was rare in O-EC and EM-EC (7.7% and 4.5%) and undetectable in HGSC
      cases. Thyroid transcription factor 1 was not expressed in O-CCC but was detected
      in 1 (6.7%) of 15 EM-CCC, 3 (23.1%) of 13 O-EC, 2 (5.1%) of 39 HGSC, and 1 (4.5%)
      of 22 EM-EC cases. All 111 cases examined were positive for PAX8, whereas 3
      (20.0%) of 15 of EM-CCC and 1 (4.5%) of 22 EM-EC cases were negative for CA125.
      There were no napsin A/TTF-1 double-positive cases, except for 1 EM-CCC, in which
      cells had a focal expression pattern. All napsin A- and/or TTF-1-positive cases
      expressed PAX8 and CA125. In conclusion, napsin A is frequently expressed in O
      CCC and EM-CCC, rarely in O-EC and EM-EC, and never in HGSC cases. These findings
      confirm the importance of using a panel of antibodies that includes napsin A, TTF
      1, and PAX8 when evaluating metastatic carcinomas of unknown origin, particularly
      when gynecologic and pulmonary adenocarcinomas are included in the differential
      diagnosis. 

PMID- 25971547
TI  - Decreased H2B monoubiquitination and overexpression of ubiquitin-specific
      protease enzyme 22 in malignant colon carcinoma.
AB  - This study aimed to evaluate the expression of H2B monoubiquitination enzyme
      (uH2B) and ubiquitin-specific protease enzyme 22 (USP22) in colon carcinoma and
      establish a correlation between the expression of these enzymes and
      clinicopathological parameters. The modification levels of uH2B and USP22 in 20
      noncancerous and 129 cancerous colon samples were studied by
      immunohistochemistry. We used a dual-rated semiquantitative method to classify
      the expression according to 3 levels and analyzed these results. uH2B was
      abundant in the normal colon epithelium, but its expression was decreased in
      colon cancers (P < .001); the uH2B modification level correlated with tumor
      differentiation (P < .001), lymph node metastasis (P = .017), distant metastasis
      (P = .036), and tumor stage (P = .039). The USP22 expression in colon carcinoma
      was higher than that in normal tissues (P = .007) and negatively correlated with
      the degree of differentiation (P = .006), invasion (P = .025), lymph node
      metastasis (P = .026), and tumor stage (P = .044). uH2B and USP22 expression
      negatively correlated (r = -0.401, P < .001). Patients with uH2B-negative and
      USP22-positive staining were found to have lower survival rates (30.737 +/- 2.866
      versus 51.667 +/- 2.286 months, P < .001). Positive uH2B and negative USP22
      expression remained a statistically significant prognostic indicator in a
      multivariate Cox regression analysis (hazard ratio, 2.557; 95% confidence
      interval, 1.043-6.269; P = .04). We conclude that uH2B displays differential
      staining patterns according to progressive stages of colon cancer, indicating
      that uH2B may play an important inhibitory role in carcinogenesis. Increased
      USP22 expression in colon cancer correlated with reduced uH2B expression, and
      this expression pattern may contribute to tumor progression. 

PMID- 25971548
TI  - Screening of cyanobacterial extracts for synthesis of silver nanoparticles.
AB  - Improvement of reliable and eco-friendly process for synthesis of metallic
      nanoparticles is a significant step in the field of application nanotechnology.
      One approach that shows vast potential is based on the biosynthesis of
      nanoparticles using micro-organisms. In this study, biosynthesis of silver
      nanoparticles (AgNP) using 30 cyanobacteria were investigated. Cyanobacterial
      aqueous extracts were subjected to AgNP synthesis at 30  degrees C. Scanning of
      these aqueous extracts containing AgNP in UV-Visible range showed single peak.
      The lambda max for different extracts varied and ranged between 440 and 490 nm
      that correspond to the "plasmon absorbance" of AgNP. Micrographs from scanning
      electron microscope of AgNP from cyanobacterial extracts showed that though
      synthesis of nanoparticles occurred in all strains but their reaction time, shape
      and size varied. Majority of the nanoparticles were spherical. Time taken for
      induction of nanoparticles synthesis by cyanobacterial extracts ranged from 30 to
      360 h and their size from 38 to 88 nm. In terms of size Cylindrospermum stagnale
      NCCU-104 was the best organism with 38 and 40 nm. But in terms of time
      Microcheate sp. NCCU-342 was the best organism as it took 30 h for AgNP
      synthesis.

PMID- 25971549
TI  - Evidence That Chlorinated Auxin Is Restricted to the Fabaceae But Not to the
      Fabeae.
AB  - Auxin is a pivotal plant hormone, usually occurring in the form of indole-3
      acetic acid (IAA). However, in maturing pea (Pisum sativum) seeds, the level of
      the chlorinated auxin, 4-chloroindole-3-acetic acid (4-Cl-IAA), greatly exceeds
      that of IAA. A key issue is how plants produce halogenated compounds such as 4-Cl
      IAA. To better understand this topic, we investigated the distribution of the
      chlorinated auxin. We show for the first time, to our knowledge, that 4-Cl-IAA is
      found in the seeds of Medicago truncatula, Melilotus indicus, and three species
      of Trifolium. Furthermore, we found no evidence that Pinus spp. synthesize 4-Cl
      IAA in seeds, contrary to a previous report. The evidence indicates a single
      evolutionary origin of 4-Cl-IAA synthesis in the Fabaceae, which may provide an
      ideal model system to further investigate the action and activity of halogenating
      enzymes in plants. 

PMID- 25971550
TI  - The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene
      Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza.
AB  - Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex
      symbiotic interface over which nutrients are exchanged between the plant host and
      the AM fungus. Dozens of genes in the host are required for the establishment and
      functioning of the interaction, among them nutrient transporters that mediate the
      uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated
      in a genetic mutant screen a petunia (Petunia hybrida) Gibberellic Acid
      Insensitive, Repressor of Gibberellic Acid Insensitive, and Scarecrow (GRAS)-type
      transcription factor, Atypical Arbuscule (ATA), that acts as the central
      regulator of AM-related genes and is required for the morphogenesis of
      arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants
      revealed an additional role of ATA in restricting mycorrhizal colonization of the
      root meristem. The lack of ATA, which represents the ortholog of Required For
      Arbuscular Mycorrhiza1 in Medicago truncatula, renders the interaction completely
      ineffective, hence demonstrating the central role of AM-related genes for
      arbuscule development and function.

PMID- 25971551
TI  - Binary 2in1 Vectors Improve in Planta (Co)localization and Dynamic Protein
      Interaction Studies.
AB  - Fluorescence-based protein-protein interaction techniques are vital tools for
      understanding in vivo cellular functions on a mechanistic level. However, only
      under the condition of highly efficient (co)transformation and accumulation can
      techniques such as Forster resonance energy transfer (FRET) realize their
      potential for providing highly accurate and quantitative interaction data. FRET
      as a fluorescence-based method unifies several advantages, such as measuring in
      an in vivo environment, real-time context, and the ability to include transient
      interactions as well as detecting the mere proximity of proteins. Here, we
      introduce a novel vector set that incorporates the benefit of the recombination
      based 2in1 cloning system with the latest state-of-the-art fluorescent proteins
      for optimal coaccumulation and FRET output studies. We demonstrate its utility
      across a range of methods. Merging the 2in1 cloning system with new-generation
      FRET fluorophore pairs allows for enhanced detection, speeds up the preparation
      of clones, and enables colocalization studies and the identification of
      meaningful protein-protein interactions in vivo. 

PMID- 25971552
TI  - Agroforestry systems of the lowland alluvial valleys of the Tehuacan-Cuicatlan
      Biosphere Reserve: an evaluation of their biocultural capacity.
AB  - BACKGROUND: Agroforestry systems (AFS) are valuable production systems that allow
      concealing benefits provision with conservation of biodiversity and ecosystem
      services. We analysed AFS of the zone of alluvial valleys of the Tehuacan
      Cuicatlan Valley (TCV), Mexico, the most intensive agricultural systems within a
      region recognized for harbouring one of the most ancient agricultural experience
      of the New World. We hypothesized that the biodiversity conservation capacity of
      AFS would be directly related to traditional agricultural features and inversely
      related to management intensity. METHODS: Agricultural practices, use frequency
      of machinery and chemical inputs, and proportion of forest and cultivated areas
      were described in 15 AFS plots in alluvial valleys of the Salado River in three
      villages of the region. With the information, we constructed a management
      intensity index and compared among plots and villages. We documented the reasons
      why people maintain wild plant species and traditional practices. Perennial plant
      species were sampled in vegetation of AFS (15 plots) and unmanaged forests (12
      plots 500 m(2)) in order to compare richness, diversity and other ecological
      indicators in AFS and forest. RESULTS: In all studied sites, people combine
      traditional and intensive agricultural practices. Main agroforestry practices are
      ground terraces and borders surrounding AFS plots where people maintain
      vegetation. According to people, the reasons for maintaining shrubs and trees in
      AFS were in order of importance are: Beauty and shade provision (14% of people),
      fruit provision (7%), protection against strong wind, and favouring water and
      soil retention. We recorded 66 species of trees and shrubs in the AFS studied,
      81% of them being native species that represent 38% of the perennial plant
      species recorded in forests sampled. Land tenure and institutions vary among
      sites but not influenced the actions for maintaining the vegetation cover in AFS.
      Plant diversity decreased with increasing agricultural intensity. CONCLUSIONS:
      Maintenance of vegetation cover did not confront markedly with the intensive
      agricultural practices. It is possible the expansion and enrichment of vegetation
      in terraces and borders of AFS. Information available on plant species and local
      techniques is potentially useful for a regional program of biodiversity
      conservation considering AFS as keystones.

PMID- 25971553
TI  - The quality of childbirth care in China: women's voices: a qualitative study.
AB  - BACKGROUND: In the context of improved utilisation of health care and outcomes,
      rapid socio-economic development and health system reform in China, it is timely
      to consider the quality of services. Data on quality of maternal health care as
      experienced by women is limited. This study explores women's expectations and
      experiences of the quality of childbirth care in rural China. METHODS: Thirty
      five semi-structured interviews and five focus group discussions were conducted
      with 69 women who had delivered in the past 12 months in hospitals in a rural
      County in Anhui Province. Data were transcribed, translated and analysed using
      the framework approach. RESULTS: Hospital delivery was preferred because it was
      considered safe. Home delivery was uncommon and unsupported by the health system.
      Expectations such as having skilled providers and privacy during childbirth were
      met. However, most women reported lack of cleanliness, companionship during
      labour, pain relief, and opportunity to participate in decision making as poor
      aspects of care. Absence of pain relief is one reason why women may opt for a
      caesarean section. CONCLUSIONS: These findings illustrate that to improve quality
      of care it is crucial to build accountability and communication between
      providers, women and their families. Ensuring women's participation in decision
      making needs to be addressed.

PMID- 25971555
TI  - World No Tobacco Day reminds us of the desolating effects of smoking on health.

PMID- 25971556
TI  - Global advocacy for controlling the tobacco industry.

PMID- 25971554
TI  - Expression of folate receptors alpha and beta in normal and cancerous gynecologic
      tissues: correlation of expression of the beta isoform with macrophage markers.
AB  - BACKGROUND: Folate receptor alpha (FOLR1/FRA) is expressed in a number of
      epithelial cancers and in particular epithelial ovarian cancer (EOC), especially
      of the serous histotype. Recent studies have shown that EOC originates from the
      fallopian tube fimbriae rather than from epithelial cells lining the ovary. We
      have previously shown by immunohistochemistry a strong correlation between FRA
      expression in EOC and normal and fallopian adenocarcinoma. Folate receptor beta
      (FOLR2/FRB) has been described to be expressed by macrophages both in
      inflammatory disorders and certain epithelial cancers. Given the high sequence
      identity of these two folate receptor family members we sought to investigate the
      architectural and cell-specific expression of these two receptors in gynecologic
      tissues. METHODS: RNA scope, a novel chromogenic in situ hybridization assay
      tool, was used to examine expression of the alpha (FOLR1) and beta (FOLR2)
      isoforms of folate receptor relative to each other as well as to the macrophage
      markers CD11b and CD68, in samples of normal fallopian tube and fallopian
      adenocarcinoma as well as normal ovary and EOC. RESULTS: We demonstrated
      expression of both FOLR1 and FOLR2 in EOC, normal fallopian tube and fallopian
      adenocarcinoma tissue while very little expression of either marker was observed
      in normal ovary. Furthermore, FOLR2 was shown to be expressed almost exclusively
      in macrophages, of both the M1 and M2 lineages, as determined by co-expression of
      CD11b and/or CD68, with little or no expression in epithelial cells. CONCLUSIONS:
      These findings further substantiate the hypothesis that the cell of origin of EOC
      is tubal epithelium and that the beta isoform of folate receptor is primarily
      restricted to macrophages. Further, macrophages expressing FOLR2 may represent
      tumor associated or infiltrating macrophages (TAMs) in epithelial cancers.

PMID- 25971557
TI  - Rural and remote health: a progress report.

PMID- 25971558
TI  - Proton pump inhibitors: too much of a good thing?

PMID- 25971560
TI  - The future of electronic cigarette growth depends on youth uptake.

PMID- 25971561
TI  - Securing a rural health workforce for the next generation of rural Australians.

PMID- 25971562
TI  - Controversies and consensus regarding vitamin D deficiency in 2015: whom to test
      and whom to treat?

PMID- 25971563
TI  - Joining the dots for the management of clinically severe obesity.

PMID- 25971564
TI  - Enabling the success of academic health science centres in Australia: where is
      the leadership?

PMID- 25971565
TI  - Can Australia's clinical practice guidelines be trusted?

PMID- 25971566
TI  - Closing the dental divide.

PMID- 25971567
TI  - Closing the dental divide.

PMID- 25971568
TI  - Determinants of rural practice: positive interaction between rural background and
      rural undergraduate training.

PMID- 25971569
TI  - Determinants of rural practice: positive interaction between rural background and
      rural undergraduate training.

PMID- 25971570
TI  - HCV-infected patients need access now to new direct-acting antiviral agents to
      avert liver-related deaths.

PMID- 25971571
TI  - A minimalist legislative solution to the problem of euthanasia.
AB  - Intense debate has continued for many years about whether voluntary euthanasia or
      assisted suicide should be permitted by law. The community is bitterly divided
      and there has been vigorous opposition from medical practitioners and the
      Australian Medical Association. Despite differences of religious and
      philosophical convictions and ethical values, there is widespread community
      agreement that people with terminal illnesses are entitled to adequate treatment,
      and should also be allowed to make basic choices about when and how they die. A
      problem with the current law is that doctors who follow current best practice
      cannot be confident that they will be protected from criminal prosecution. We
      propose simple changes to Commonwealth and state legislation that recognise
      community concerns and protect doctors acting in accordance with best current
      practice. This minimalist solution should be widely acceptable to the community,
      including both the medical profession and those who object to euthanasia for
      religious reasons. Important areas of disagreement will persist that can be
      addressed in future debates. 

PMID- 25971572
TI  - Strengthening primary health care: achieving health gains in a remote region of
      Australia.
AB  - OBJECTIVE: To evaluate the impact of a comprehensive primary health care service
      model on key health performance indicators in a remote region of Australia.
      DESIGN AND SETTING: A cross-sectional 6-year retrospective evaluation of the
      results of a health service partnership between an Aboriginal community
      controlled health service, a hospital and a community health service in north
      west Western Australia. INTERVENTION: Integration of health promotion, health
      assessments and chronic disease management with an acute primary health care
      service as a result of the formal partnership. MAIN OUTCOME MEASURES: Cross
      sectional data on use and outcomes of health care from 1 July 2006 to 30 June
      2012 are reported in accordance with national key performance indicators.
      RESULTS: There were increases in occasions of service (from 21 218 to 33 753),
      most notably in primary health care services provided to very remote outlying
      communities (from 863 to 11 338). Health assessment uptake increased from 13% of
      the eligible population to 61%, leading to 73% of those identified with diabetes
      being placed on a care plan. Quality-of-care indicators (glycated haemoglobin
      checks and proportion of people with diabetics receiving antihypertensives)
      showed improvements over the 6-year study period, and there was also a downward
      trend in mortality. CONCLUSIONS: This study demonstrates that strengthening
      primary health care services by addressing key enablers and sustainability
      requirements can translate into population health gains consistent with the goals
      underpinning the National Health Care Reform and Closing the Gap policies, and
      may potentially reduce health inequity for remote-living Aboriginal Australians.

PMID- 25971573
TI  - The use of financial incentives in Australian general practice.
AB  - OBJECTIVE: To examine the uptake of financial incentive payments in general
      practice, and identify what types of practitioners are more likely to participate
      in these schemes. DESIGN AND SETTING: Analysis of data on general practitioners
      and GP registrars from the Medicine in Australia - Balancing Employment and Life
      (MABEL) longitudinal panel survey of medical practitioners in Australia, from
      2008 to 2011. MAIN OUTCOME MEASURES: Income received by GPs from government
      incentive schemes and grants and factors associated with the likelihood of
      claiming such incentives. RESULTS: Around half of GPs reported receiving income
      from financial incentives in 2008, and there was a small fall in this proportion
      by 2011. There was considerable movement into and out of the incentives schemes,
      with more GPs exiting than taking up grants and payments. GPs working in larger
      practices with greater administrative support, GPs practising in rural areas and
      those who were principals or partners in practices were more likely to use grants
      and incentive payments. CONCLUSIONS: Administrative support available to GPs
      appears to be an increasingly important predictor of incentive use, suggesting
      that the administrative burden of claiming incentives is large and not always
      worth the effort. It is, therefore, crucial to consider such costs (especially
      relative to the size of the payment) when designing incentive payments. As market
      conditions are also likely to influence participation in incentive schemes, the
      impact of incentives can change over time and these schemes should be reviewed
      regularly.

PMID- 25971574
TI  - Eagle Syndrome as a potential cause of Tapia Syndrome.

PMID- 25971575
TI  - Asthma control in Australia: a cross-sectional web-based survey in a nationally
      representative population.
AB  - OBJECTIVE: To identify patterns of asthma control and treatment in Australian
      adults with asthma. DESIGN: Cross-sectional web-based survey, conducted 1-27
      November 2012. PARTICIPANTS: Adults with current asthma, at least 16 years of
      age, drawn randomly from a web-based panel and weighted to reflect national
      population proportions for people with asthma. MAIN OUTCOME MEASURES: Asthma
      Control Test (ACT) scores; health care utilisation; medication use. RESULTS: 2686
      participants completed the survey (57.1% female; median age group, 40-49 years).
      Mean ACT score was 19.2 (95% CI, 18.9-19.3), with asthma classified as "well
      controlled" for 54.4% of participants, "not well controlled" for 22.7% and "very
      poorly controlled" for 23.0%. 60.8% reported using preventer medication (mostly
      combined inhaled corticosteroid/long-acting beta2-agonist) during the previous
      year. 23.4% had made at least one urgent visit to a general practitioner
      concerning their asthma, 10.0% at least one emergency department visit. Urgent
      consultations were more common for "very poorly controlled" than "well
      controlled" asthma (adjusted odds ratio, urgent GP visits 5.98 [95% CI, 4.75
      7.54] and emergency department visits 2.59 [95% CI, 1.91-3.53] respectively).
      Participants were classified according to asthma symptom control and frequency of
      preventer medication usage: Those with "well controlled" asthma included Group A
      (40.0% of participants) who used preventer medication infrequently (less than 5
      days a week) or not at all, consistent with mild asthma, and Group B (14.7%), who
      used it at least 5 days a week. Uncontrolled asthma symptoms were reported by
      Group C (19.7%) despite regular preventer use, and by Group D (25.7%), who used
      none or little. CONCLUSIONS: This study provides the first data about asthma
      control and its relationship with treatment in a large representative Australian
      population. The findings highlight significant preventable asthma morbidity in
      Australia.

PMID- 25971576
TI  - The trumpet's blown pupil.

PMID- 25971577
TI  - Warfarin-induced skin necrosis following recommencement of warfarin after
      perioperative Prothrombinex-VF.

PMID- 25971580
TI  - Ultra-small superparamagnetic iron oxide mediated magnetic hyperthermia in
      treatment of neck lymph node metastasis in rabbit pyriform sinus VX2 carcinoma.
AB  - Lymph node metastasis of rabbit VX2 pyriform sinus carcinoma can be enhanced by
      MR scanning after injecting ultra-small superparamagnetic iron oxide (USPIO) into
      the submucosa beside the tumor. The metastasis lymph node which fit in with the
      diagnostic criteria will be placed into the alternating magnetic field after MR
      scanning. Then, magnetic particles can be heated to the effective therapeutic
      temperature. And it evaluates the possibility of diagnosis together with therapy
      in cervical metastasis of pyriform sinus carcinoma. Twenty rabbits bearing VX2
      tumor in pyriform sinuses were randomly divided into hyperthermia group and
      control group after USPIO MR scanning; each group contained 10 rabbits. The
      hyperthermia for the experimental group was conducted by the alternating magnetic
      field. After hyperthermia, the detection of apoptosis for the two groups was
      tested by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end
      labeling (TUNEL), transmission electron microscopy (TEM), and the expression of
      Bcl-2 and Bax evaluated by immunohistochemical analysis. The apoptosis rate
      detected by TUNEL in hyperthermia group was 100 %, while the control group was
      only 20 % (p < 0.05). TEM observation showed that cell chromatin condensation and
      clumping, condensed cytoplasm, endoplasmic reticulum membrane fusion with loose
      change, and the formation of a bubble could be seen in the hyperthermia group.
      However, the control group showed a more complete cytoplasm and nucleus. Bcl-2
      protein expression in the hyperthermia group was lower than the control group,
      and Bax protein expression in hyperthermia group was higher (p < 0.05). USPIO
      indirect lymphography could localize the metastatic lymph nodes for hyperthermia.
      And it could make the metastatic cervical lymph nodes apoptosis when placed into
      the alternating magnetic field.

PMID- 25971581
TI  - Promyelocytic leukemia protein enhances apoptosis of gastric cancer cells through
      Yes-associated protein.
AB  - It has been shown that Yes-associated protein (YAP) acts as a transcriptional co
      activator to regulate p73-dependent apoptosis in response to DNA damage in some
      cell types, and promyelocytic leukemia (PML) protein is involved in the
      regulation loop through stabilization of YAP through sumoylation. Although YAP
      has been shown to be significantly upregulated in gastric cancer, whether the
      YAP/PML/p73 regulation loop also functions in gastric cancer is unknown. Here, we
      show significantly higher levels of YAP and significantly lower levels of PML in
      the gastric cancer specimen. Overexpression of YAP in gastric cancer cells
      significantly increased cell growth, but did not affect apoptosis. However,
      overexpression of PML in gastric cancer cells significantly increased cell
      apoptosis, resulting in decreases in cell growth, which seemed to require the
      presence of YAP. The effect of PML on apoptosis appeared to be conducted through
      p73-mediated modulation of apoptosis-associated genes, Bcl-2, Bak, and caspase9.
      Thus, our study suggests the presence of a YAP/PML/p73 regulatory loop in gastric
      cancer, and highlights PML as a promising tumor suppressor in gastric cancer
      through YAP-coordinated cancer cell apoptosis.

PMID- 25971582
TI  - Reduced expression of the long non-coding RNA AI364715 in gastric cancer and its
      clinical significance.
AB  - Long non-coding RNA (lncRNA), which is greater than 200 nucleotides, is a class
      of RNA molecules without protein coding function. In recent years, studies have
      shown that lncRNAs are associated with cancers. They are affecting the occurrence
      and development of cancers. However, the diagnostic significances of lncRNAs in
      gastric cancer are largely unknown. In this study, we focused on AI364715, one
      typical lncRNA. A total of 186 samples were collected from two cancer centers. To
      find the potential association between its level and gastric cancer, we first
      collected 75 paired gastric cancer tissues and normal tissues, which are 5 cm
      away from the edge of carcinoma. Besides, 18 human healthy gastric mucosa and 18
      gastric precancerous lesions (dysplasia) were also collected. Quantitative
      reverse transcription-polymerase chain reaction (RT-PCR) was first used to detect
      the expression level of AI364715 at multiple stages of gastric tumorigenesis.
      Then, the relationships between AI364715 level and the clinicopathological
      factors of patients with gastric cancer were analyzed. The results showed that
      the expression level of AI364715 in gastric cancer tissues was downregulated.
      Meanwhile, its expression level was closely associated with tumor size and
      differentiation. More importantly, AI364715 expression level was significantly
      changed in dysplasia, the typical precancerous lesions. Taken together, AI364715
      may be a potential biomarker for the diagnosis of gastric cancer.

PMID- 25971583
TI  - Decreased expression of SOX17 is associated with tumor progression and poor
      prognosis in breast cancer.
AB  - The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of
      biological processes and is related to the tumorigenesis and progression of
      multiple tumors. However, the clinical application of SOX17 for breast cancer
      prognosis is currently limited. The aim of this study was to investigate the
      clinicopathologic and prognostic significance of SOX17 expression in human breast
      cancer. qPCR and western blot assays were performed to measure the expression of
      SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and
      corresponding noncancerous tissues. A SOX17 overexpression cell model was used to
      examine changes in cell growth in vitro. Immunohistochemical analyses were
      performed to retrospectively examine the prognostic impact of SOX17 expression in
      187 additional breast cancer patients. Our results showed that SOX17 expression
      was decreased at both the messenger RNA (mRNA) and protein levels in the breast
      cancer cell lines and tissues, and that SOX17 overexpression could strongly
      suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression
      was strongly correlated with higher tumor grade (P = 0.002), lymph node
      metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had
      poorer disease-free survival (DFS) and overall survival (OS) compared to normal
      SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate
      analyses indicated that lower SOX17 expression was an independent prognostic
      factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR
      = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that
      SOX17 expression is a useful prognostic biomarker for breast cancer.

PMID- 25971585
TI  - Evaluation of genotoxicity in workers exposed to low levels of formaldehyde in a
      furniture manufacturing facility.
AB  - Formaldehyde (FA) is a chemical widely used in the furniture industry and has
      been classified as a potential human carcinogen. The purpose of this study was to
      evaluate the occupational exposure of workers to FA at a furniture manufacturing
      facility and the relationship between environmental concentrations of FA, formic
      acid concentration in urine, and DNA damage. The sample consisted of 46 workers
      exposed to FA and a control group of 45 individuals with no history of
      occupational exposure. Environmental concentrations of FA were determined by high
      performance liquid chromatography. Urinary formic acid concentrations were
      determined by gas chromatography with flame ionization detector. DNA damage was
      evaluated by the micronucleus (MN) test performed in exfoliated buccal cells and
      comet assay with venous blood. The 8-h time-weighted average of FA environmental
      concentration ranged from 0.03 ppm to 0.09 ppm at the plant, and the control
      group was exposed to a mean concentration of 0.012 ppm. Workers exposed to higher
      environmental FA concentrations had urinary formic acid concentrations
      significantly different from those of controls (31.85 mg L(-1) vs. 19.35 mg L(-),
      p <= 0.01 Mann-Whitney test). Significant differences were found between control
      and exposed groups for the following parameters: damage frequency and damage
      index in the comet assay, frequency of binucleated cells in the MN test, and
      formic acid concentration in urine. The frequency of micronuclei, nuclear buds,
      and karyorrhexis did not differ between groups. There was a positive correlation
      between environmental concentrations of FA and damage frequency (Spearman's rank
      correlation coefficient [r s] = 0.24), damage index (r s = 0.21), binucleated
      cells (r s = 0.34), and urinary formic acid concentration (r s = 0.63). The
      results indicate that, although workers in the furniture manufacturing facility
      were exposed to low environmental levels of FA, this agent contributes to the
      observed increase in cytogenetic damage. In addition, urinary formic acid
      concentrations correlated strongly with occupational exposure to FA. 

PMID- 25971584
TI  - Air toxics and birth defects: a Bayesian hierarchical approach to evaluate
      multiple pollutants and spina bifida.
AB  - BACKGROUND: While there is evidence that maternal exposure to benzene is
      associated with spina bifida in offspring, to our knowledge there have been no
      assessments to evaluate the role of multiple hazardous air pollutants (HAPs)
      simultaneously on the risk of this relatively common birth defect. In the current
      study, we evaluated the association between maternal exposure to HAPs identified
      by the United States Environmental Protection Agency (U.S. EPA) and spina bifida
      in offspring using hierarchical Bayesian modeling that includes Stochastic Search
      Variable Selection (SSVS). METHODS: The Texas Birth Defects Registry provided
      data on spina bifida cases delivered between 1999 and 2004. The control group was
      a random sample of unaffected live births, frequency matched to cases on year of
      birth. Census tract-level estimates of annual HAP levels were obtained from the
      U.S. EPA's 1999 Assessment System for Population Exposure Nationwide. Using the
      distribution among controls, exposure was categorized as high exposure (>95(th)
      percentile), medium exposure (5(th)-95(th) percentile), and low exposure (<5(th)
      percentile, reference). We used hierarchical Bayesian logistic regression models
      with SSVS to evaluate the association between HAPs and spina bifida by computing
      an odds ratio (OR) for each HAP using the posterior mean, and a 95% credible
      interval (CI) using the 2.5(th) and 97.5(th) quantiles of the posterior samples.
      Based on previous assessments, any pollutant with a Bayes factor greater than 1
      was selected for inclusion in a final model. RESULTS: Twenty-five HAPs were
      selected in the final analysis to represent "bins" of highly correlated HAPs (rho
      > 0.80). We identified two out of 25 HAPs with a Bayes factor greater than 1:
      quinoline (ORhigh = 2.06, 95% CI: 1.11-3.87, Bayes factor = 1.01) and
      trichloroethylene (ORmedium = 2.00, 95% CI: 1.14-3.61, Bayes factor = 3.79).
      CONCLUSIONS: Overall there is evidence that quinoline and trichloroethylene may
      be significant contributors to the risk of spina bifida. Additionally, the use of
      Bayesian hierarchical models with SSVS is an alternative approach in the
      evaluation of multiple environmental pollutants on disease risk. This approach
      can be easily extended to environmental exposures, where novel approaches are
      needed in the context of multi-pollutant modeling.

PMID- 25971586
TI  - Lucentis excluded from WHO list of essential medicines.

PMID- 25971587
TI  - Anatomy packing with hierarchical segments: an algorithm for segmentation of
      pulmonary nodules in CT images.
AB  - BACKGROUND: This paper proposes a semantic segmentation algorithm that provides
      the spatial distribution patterns of pulmonary ground-glass nodules with solid
      portions in computed tomography (CT) images. METHODS: The proposed segmentation
      algorithm, anatomy packing with hierarchical segments (APHS), performs pulmonary
      nodule segmentation and quantification in CT images. In particular, the APHS
      algorithm consists of two essential processes: hierarchical segmentation tree
      construction and anatomy packing. It constructs the hierarchical segmentation
      tree based on region attributes and local contour cues along the region
      boundaries. Each node of the tree corresponds to the soft boundary associated
      with a family of nested segmentations through different scales applied by a
      hierarchical segmentation operator that is used to decompose the image in a
      structurally coherent manner. The anatomy packing process detects and localizes
      individual object instances by optimizing a hierarchical conditional random field
      model. Ninety-two histopathologically confirmed pulmonary nodules were used to
      evaluate the performance of the proposed APHS algorithm. Further, a comparative
      study was conducted with two conventional multi-label image segmentation
      algorithms based on four assessment metrics: the modified Williams index,
      percentage statistic, overlapping ratio, and difference ratio. RESULTS: Under the
      same framework, the proposed APHS algorithm was applied to two clinical
      applications: multi-label segmentation of nodules with a solid portion and
      surrounding tissues and pulmonary nodule segmentation. The results obtained
      indicate that the APHS-generated boundaries are comparable to manual delineations
      with a modified Williams index of 1.013. Further, the resulting segmentation of
      the APHS algorithm is also better than that achieved by two conventional multi
      label image segmentation algorithms. CONCLUSIONS: The proposed two-level
      hierarchical segmentation algorithm effectively labelled the pulmonary nodule and
      its surrounding anatomic structures in lung CT images. This suggests that the
      generated multi-label structures can potentially serve as the basis for
      developing related clinical applications.

PMID- 25971589
TI  - Bone resorption during the first year after implantation of a single-segment
      dynamic interspinous stabilization device and its risk factors.
AB  - BACKGROUND: Dynamic interspinous stabilization devices generally provide
      satisfactory results, but can result in recurrent lumbar disc herniation, spinous
      process fracture, or bone resorption of the spinous process. The purpose of this
      study was to investigate if the Wallis dynamic stabilization device is associated
      with bone resorption. METHODS: Patients who underwent single-segment posterior
      lumbar decompression and implantation of a Wallis dynamic interspinous
      stabilization device at the L4/5 level between January 1, 2009 and October 1,
      2011 were included. Bone resorption rate, Oswestry Disability Index (ODI),
      Japanese Orthopedic Association (JOA) score, and visual analogue scale (VAS) pain
      score were measured. Patient baseline and 1-year follow-up data were collected
      and analyzed. The bone resorption rate of the L4 and L5 spinous processes was
      calculated. RESULTS: Twenty four males and 20 females with a mean age of 42.7 +/-
      14.7 years were included. Twenty nine patients had significant bone resorption
      (bone resorption rate > 20%) and 15 had no bone resorption (bone resorption rate
      <= 20%) at 1 year after surgery. Lumbar lordosis >= 50 degrees  was associated
      with a lower bone resorption than lumbar lordosis < 50 degrees  and increasing
      BMI was associated with increased bone resorption. There were no significant
      differences between the bone resorption and no bone resorption groups in the
      improvement rate of VAS pain score, ODI, and JOA score at 1 year after surgery.
      CONCLUSIONS: Significant bone resorption occurs within 1 year after implantation
      of the Wallis device in more than 50% of patients. However, it does not affect
      short-term functional results.

PMID- 25971588
TI  - Fungal traits that drive ecosystem dynamics on land.
AB  - Fungi contribute extensively to a wide range of ecosystem processes, including
      decomposition of organic carbon, deposition of recalcitrant carbon, and
      transformations of nitrogen and phosphorus. In this review, we discuss the
      current knowledge about physiological and morphological traits of fungi that
      directly influence these processes, and we describe the functional genes that
      encode these traits. In addition, we synthesize information from 157 whole fungal
      genomes in order to determine relationships among selected functional genes
      within fungal taxa. Ecosystem-related traits varied most at relatively coarse
      taxonomic levels. For example, we found that the maximum amount of variance for
      traits associated with carbon mineralization, nitrogen and phosphorus cycling,
      and stress tolerance could be explained at the levels of order to phylum.
      Moreover, suites of traits tended to co-occur within taxa. Specifically, the
      genetic capacities for traits that improve stress tolerance-beta-glucan
      synthesis, trehalose production, and cold-induced RNA helicases-were positively
      related to one another, and they were more evident in yeasts. Traits that
      regulate the decomposition of complex organic matter-lignin peroxidases,
      cellobiohydrolases, and crystalline cellulases-were also positively related, but
      they were more strongly associated with free-living filamentous fungi.
      Altogether, these relationships provide evidence for two functional groups:
      stress tolerators, which may contribute to soil carbon accumulation via the
      production of recalcitrant compounds; and decomposers, which may reduce soil
      carbon stocks. It is possible that ecosystem functions, such as soil carbon
      storage, may be mediated by shifts in the fungal community between stress
      tolerators and decomposers in response to environmental changes, such as drought
      and warming. 

PMID- 25971590
TI  - Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation.
AB  - Although alcohol consumption is linked to increased aggression, its neural
      correlates have not directly been studied in humans so far. Based on a
      comprehensive neurobiological model of alcohol-induced aggression, we
      hypothesized that alcohol-induced aggression would go along with increased
      amygdala and ventral striatum reactivity and impaired functioning of the
      prefrontal cortex (PFC) under alcohol. We measured neural and behavioral
      correlates of alcohol-induced aggression in a provoking vs non-provoking
      condition with a variant of the Taylor aggression paradigm (TAP) allowing to
      differentiate between reactive (provoked) and proactive (unprovoked) aggression.
      In a placebo-controlled cross-over design with moderate alcohol intoxication
      (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic
      resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking
      conditions and alcohol vs placebo increased aggression and decreased brain
      responses in the anterior cingulate cortex/dorso-medial PFC (provoking<non
      provoking) and the ventral striatum (alcohol<placebo) across our healthy sample.
      Interestingly, alcohol specifically increased proactive (unprovoked) but not
      reactive (provoked) aggression (alcohol * provocation interaction). However,
      investigation of inter-individual differences revealed (1) that pronounced
      alcohol-induced proactive aggression was linked to higher levels of aggression
      under placebo, and (2) that pronounced alcohol-induced reactive aggression was
      related to increased amygdala and ventral striatum reactivity under alcohol,
      providing evidence for their role in human alcohol-induced reactive aggression.
      Our findings suggest that in healthy young adults a liability for alcohol-induced
      aggression in a non-provoking context might depend on overall high levels of
      aggression, but on alcohol-induced increased striatal and amygdala reactivity
      when triggered by provocation.

PMID- 25971591
TI  - Excitatory Transmission to the Lateral Habenula Is Critical for Encoding and
      Retrieval of Spatial Memory.
AB  - The lateral habenula (LHb) is viewed as a relay between the limbic system, the
      basal ganglia (BG), and monoaminergic neurons of the midbrain. If a prominent
      role has been evidenced in BG-mediated functions such as value-based decision
      making, very little is known about the involvement of the LHb in limbic functions
      such as memory processing. In the present study, we used two pharmacological
      approaches-LHb reversible inactivation with intra-LHb infusion of muscimol, an
      agonist of the GABA-A receptor, or blockade of excitatory inputs with intra-LHb
      infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of the
      glutamatergic AMPA receptor-to investigate the involvement of the LHb in
      encoding, consolidation, and retrieval of spatial memory in the water maze (WM)
      in rats. We found that intra-LHb infusion of muscimol or CNQX prevented encoding
      and retrieval, but not consolidation of spatial information. In addition,
      muscimol but not CNQX induced impairments during a cued version of the WM task,
      and marked anxiety in the elevated plus maze. These results confirm the
      involvement of the LHb in higher cognitive functions. They further suggest a
      dichotomy between the role of glutamatergic and other inputs to the LHb in
      hippocampus-dependent memory processing, as well as in emotional aspects of goal
      directed behaviors. 

PMID- 25971592
TI  - Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive
      Cues Through Potentiation of Phasic Dopamine Signaling.
AB  - Adolescent alcohol use remains a major public health concern due in part to well
      established findings implicating the age of onset in alcohol use in the
      development of alcohol use disorders and persistent decision-making deficits in
      adults. We have previously demonstrated that moderate adolescent alcohol
      consumption in rats promotes suboptimal decision making and an associated
      perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent
      incentive learning processes are an integral component of value-based decision
      making and a fundamental element to many theoretical accounts of addiction. Thus
      we tested the hypothesis that adolescent alcohol use selectively alters incentive
      learning processes through perturbation of mesolimbic dopamine systems. To assess
      incentive learning, behavioral and neurochemical measurements were made during
      the acquisition, maintenance, extinction, and reacquisition of a Pavlovian
      conditioned approach procedure in adult rats with a history of adolescent alcohol
      consumption. We show that moderate adolescent alcohol consumption potentiates
      stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan
      cyclic voltammetry, in adulthood and biases individuals toward a dopamine
      dependent incentive learning strategy. Moreover, we demonstrate that animals
      exposed to alcohol in adolescence are more sensitive to an unexpected variation
      in reward outcomes. This pattern of phasic dopamine signaling and the associated
      bias in learning may provide a mechanism for the well-documented vulnerability of
      individuals with early-life alcohol use for alcohol use disorders in adulthood. 

PMID- 25971593
TI  - Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala
      Inputs.
AB  - Kappa opioid receptors (KORs) have been implicated in anxiety and stress,
      conditions that involve activation of projections from the basolateral amygdala
      (BLA) to the medial prefrontal cortex (mPFC). Although KORs have been studied in
      several brain regions, their role on mPFC physiology and on BLA projections to
      the mPFC remains unclear. Here, we explored whether KORs modify synaptic inputs
      from the BLA to the mPFC using in vivo electrophysiological recordings with
      electrical and optogenetic stimulation. Systemic administration of the KOR
      agonist U69,593 inhibited BLA-evoked synaptic responses in the mPFC without
      altering hippocampus-evoked responses. Intra-mPFC U69,593 inhibited electrical
      and optogenetic BLA-evoked synaptic responses, an effect blocked by the KOR
      antagonist nor-BNI. Bilateral intra-mPFC injection of the KOR antagonist nor-BNI
      increased center time in the open field test, suggesting an anxiolytic effect.
      The data demonstrate that mPFC KORs negatively regulate glutamatergic synaptic
      transmission in the BLA-mPFC pathway and anxiety-like behavior. These findings
      provide a framework whereby KOR signaling during stress and anxiety can regulate
      the flow of emotional state information from the BLA to the mPFC. 

PMID- 25971594
TI  - High prevalence of sub-microscopic infections in Colombia.
AB  - BACKGROUND: Malaria transmission in Latin America is typically characterized as
      hypo-endemic and unstable with ~170 million inhabitants at risk of malaria
      infection. Although Colombia has witnessed an important decrease in malaria
      transmission, the disease remains a public health problem with an estimated ~10
      million people currently living in areas with malaria risk and ~61,000 cases
      reported in 2012. This study aimed to establish the malaria prevalence in three
      endemic regions of Colombia to aid in designing new interventions for malaria
      elimination. METHODS: A cross-sectional survey was conducted in three regions of
      Colombia with different malaria epidemiological profiles: Tierralta (Ta), Tumaco
      (Tu) and Buenaventura (Bv). The Annual Parasite Index (API) was 10.7, 6.9 and
      3.1, respectively. Participants were asked to respond to a sociodemographic
      questionnaire and then were bled to determine the Duffy genotype and the
      prevalence of malaria infection by microscopy and quantitative real-time PCR
      (qPCR). RESULTS: The study was conducted between October 2011 and January 2012.
      Eight sentinel sites with 1,169 subjects from 267 households were included. The
      overall prevalence of sub-microscopic infections measured by thick blood smear
      (TBS) was 0.3% (n=4) whereas by qPCR it was 9.7% (n=113), with a greater
      proportion (13%) in 40-50 years old individuals. Furthermore, different regions
      displayed different prevalence of sub-microscopic infections: Bv 12%, Ta 15%, and
      Tu 4%. From these 113 samples (qPCR), 74% were positive for P. vivax and 22% for
      P. falciparum, and 4% were mixed infections, which correlates to the overall
      parasite prevalence in Colombia. This study showed that in the southern Pacific
      coast of Colombia (Bv and Tu), around 56% of the population have a Duffy-negative
      genotype, compared to the northern region (Ta) where the percentage of Duffy
      negative genotype is around 3%. CONCLUSIONS: Sub-microscopic infections are
      prevalent across different regions in Colombia, particularly in areas with
      relatively low transmission intensity. The poor microscopy results suggest the
      need for more sensitive diagnostic tools for detection of sub-microscopic
      infections. This study underscores the importance of conducting active case
      surveillance to more accurately determine malaria incidence, and highlights the
      need for updating the malaria guidelines to track and treat sub-microscopic
      malaria infections.

PMID- 25971596
TI  - CD44 expression contributes to trastuzumab resistance in HER2-positive breast
      cancer cells.
AB  - Resistance to HER2-targeted therapies remains a major obstacle in the treatment
      of HER2-overexpressing breast cancer. CD44, a putative breast cancer stem cell
      (CSC) marker, is overexpressed in trastuzumab-resistant breast cancer cells.
      While CSC-related genes may play a role in the development of trastuzumab
      resistance, conflicting results have been published about CSC response to
      trastuzumab. We hypothesized that CD44 contributes to trastuzumab resistance
      independently of its role as a CSC marker. We used trastuzumab-sensitive breast
      cancer cell lines and their trastuzumab-resistant isogenic counterparts to
      evaluate the role of CD44 in response to trastuzumab. miRNA and mRNA expression
      were analyzed using microarray chips. A gene set enrichment analysis was created
      and matched with response to trastuzumab in cells and patient samples. The
      proportions of CSC in trastuzumab-resistant cells were similar to or lower than
      in the trastuzumab-sensitive cells. However, CD44 expression levels were
      significantly higher in both trastuzumab-resistant cell lines and its knockdown
      led to an increased response to trastuzumab. The invasiveness and anchorage
      independent growth of trastuzumab-resistant cells were higher and blocked by
      downregulation of CD44. Results also showed that CD44-related resistance to
      trastuzumab is regulated by miRNAs. We identified a CD44-related gene expression
      profile that correlated with response to trastuzumab in cell lines and breast
      cancer patients. CD44 mediates trastuzumab resistance in HER2-positive breast
      cancer cells independently of its role as a CSC marker and that this role of CD44
      is partly regulated by miRNA. 

PMID- 25971597
TI  - Two novel cardenolides from Calotropis procera.
AB  - Two new cardenolides, named ischarin and ischaridin in addition to 10 known
      compounds, were isolated from Calotropis procera Ait. (Asclepiadaceae), growing
      wild in Jordan. Their structures were established mainly by the extensive
      application of one- and two-dimensional (1)H and (13)C-NMR spectroscopy. 

PMID- 25971595
TI  - Progress and challenges in predicting protein interfaces.
AB  - The majority of biological processes are mediated via protein-protein
      interactions. Determination of residues participating in such interactions
      improves our understanding of molecular mechanisms and facilitates the
      development of therapeutics. Experimental approaches to identifying interacting
      residues, such as mutagenesis, are costly and time-consuming and thus,
      computational methods for this purpose could streamline conventional pipelines.
      Here we review the field of computational protein interface prediction. We make a
      distinction between methods which address proteins in general and those targeted
      at antibodies, owing to the radically different binding mechanism of antibodies.
      We organize the multitude of currently available methods hierarchically based on
      required input and prediction principles to provide an overview of the field. 

PMID- 25971598
TI  - Affective facilitation of early visual cortex during rapid picture presentation
      at 6 and 15 Hz.
AB  - The steady-state visual evoked potential (SSVEP), a neurophysiological marker of
      attentional resource allocation with its generators in early visual cortex,
      exhibits enhanced amplitude for emotional compared to neutral complex pictures.
      Emotional cue extraction for complex images is linked to the N1-EPN complex with
      a peak latency of ~140-160 ms. We tested whether neural facilitation in early
      visual cortex with affective pictures requires emotional cue extraction of
      individual images, even when a stream of images of the same valence category is
      presented. Images were shown at either 6 Hz (167 ms, allowing for extraction) or
      15 Hz (67 ms per image, causing disruption of processing by the following image).
      Results showed SSVEP amplitude enhancement for emotional compared to neutral
      images at a presentation rate of 6 Hz but no differences at 15 Hz. This was not
      due to featural differences between the two valence categories. Results strongly
      suggest that individual images need to be displayed for sufficient time allowing
      for emotional cue extraction to drive affective neural modulation in early visual
      cortex. 

PMID- 25971599
TI  - Neuropeptide S receptor gene variation and neural correlates of cognitive emotion
      regulation.
AB  - The neuropeptide S (NPS) and its receptor NPSR have captured attention in the
      pathogenesis of anxiety disorders. Here, a functional polymorphism in the NPSR1
      gene has been linked to deviant cortico-limbic interactions in response to
      negative stimuli. While healthy T allele carriers exhibited increased amygdala
      and prefrontal cortex activity, panic disorder patients carrying the T risk
      allele displayed hypofrontality possibly reflecting insufficient prefrontal
      inhibition of limbic reactivity. In order to study multi-level effects of
      genotype and anxiety, prefrontal cortex activity during an emotional n-back task
      was measured in 66 volunteers genotyped for the NPSR1 rs324981 A/T variant (AA
      homozygotes vs. T allele carriers) by means of functional near-infrared
      spectroscopy. For a high working memory load (3-back), T allele carriers showed a
      signal increase to negative pictures in the dorsolateral and medial prefrontal
      cortex while AA homozygotes displayed a signal decrease. Since groups did not
      differ on skin conductance level and behavioral parameters, this effect in the
      risk group in line with results from fMRI studies is speculated to represent an
      adaptive mechanism to compensate for presumably increased subcortical activity
      driven by an overactive NPS system. However, anxiety sensitivity correlated
      negatively with prefrontal activity in T allele carriers possibly suggesting a
      decompensation of the adaptive compensatory upregulation. 

PMID- 25971600
TI  - Psychopathic traits are associated with cortical and subcortical volume
      alterations in healthy individuals.
AB  - Research suggests psychopathy is associated with structural brain alterations
      that may contribute to the affective and interpersonal deficits frequently
      observed in individuals with high psychopathic traits. However, the regional
      alterations related to different components of psychopathy are still unclear. We
      used voxel-based morphometry to characterize the structural correlates of
      psychopathy in a sample of 35 healthy adults assessed with the Triarchic
      Psychopathy Measure. Furthermore, we examined the regional grey matter
      alterations associated with the components described by the triarchic model. Our
      results showed that, after accounting for variation in total intracranial volume,
      age and IQ, overall psychopathy was negatively associated with grey matter volume
      in the left putamen and amygdala. Additional regression analysis with anatomical
      regions of interests revealed total triPM score was also associated with
      increased lateral orbitofrontal cortex (OFC) and caudate volume. Boldness was
      positively associated with volume in the right insula. Meanness was positively
      associated with lateral OFC and striatum volume, and negatively associated with
      amygdala volume. Finally, disinhibition was negatively associated with amygdala
      volume. Results highlight the contribution of both subcortical and cortical brain
      alterations for subclinical psychopathy and are discussed in light of prior
      research and theoretical accounts about the neurobiological bases of psychopathic
      traits. 

PMID- 25971602
TI  - Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression
      recognition.
AB  - The orbitofrontal cortex (OFC) has been implicated in the capacity to accurately
      recognise facial expressions. The aim of the current study was to determine if
      anodal transcranial direct current stimulation (tDCS) targeting the right OFC in
      healthy adults would enhance facial expression recognition, compared with a sham
      condition. Across two counterbalanced sessions of tDCS (i.e. anodal and sham), 20
      undergraduate participants (18 female) completed a facial expression labelling
      task comprising angry, disgusted, fearful, happy, sad and neutral expressions,
      and a control (social judgement) task comprising the same expressions. Responses
      on the labelling task were scored for accuracy, median reaction time and overall
      efficiency (i.e. combined accuracy and reaction time). Anodal tDCS targeting the
      right OFC enhanced facial expression recognition, reflected in greater efficiency
      and speed of recognition across emotions, relative to the sham condition. In
      contrast, there was no effect of tDCS to responses on the control task. This is
      the first study to demonstrate that anodal tDCS targeting the right OFC boosts
      facial expression recognition. This finding provides a solid foundation for
      future research to examine the efficacy of this technique as a means to treat
      facial expression recognition deficits, particularly in individuals with OFC
      damage or dysfunction. 

PMID- 25971601
TI  - Thirst and the state-dependent representation of incentive stimulus value in
      human motive circuitry.
AB  - Depletion imposes both need and desire to drink, and potentiates the response to
      need-relevant cues in the environment. The present fMRI study aimed to determine
      which neural structures selectively increase the incentive value of need-relevant
      stimuli in a thirst state. Towards this end, participants were scanned twice-
      either in a thirst or no-thirst state--while viewing pictures of beverages and
      chairs. As expected, thirst led to a selective increase in self-reported
      pleasantness and arousal by beverages. Increased responses to beverage when
      compared with chair stimuli were observed in the cingulate cortex, insular cortex
      and the amygdala in the thirst state, which were absent in the no-thirst
      condition. Enhancing the incentive value of need-relevant cues in a thirst state
      is a key mechanism for motivating drinking behavior. Overall, distributed regions
      of the motive circuitry, which are also implicated in salience processing,
      craving and interoception, provide a dynamic body-state dependent representation
      of stimulus value.

PMID- 25971603
TI  - Use of pemetrexed for non-small cell lung cancer in the Andalusian public health
      system.
AB  - The aim of this study is to determine the profile of the use of pemetrexed in
      metastatic or locally advanced NSCLC in Andalusia and its variation over 2 years
      (2010-2011). A prescription-indication observational retrospective multicenter
      study was conducted. Adult patients with locally advanced/metastatic NSCLC who
      received pemetrexed in any hospital in the Andalusian Public Health System during
      the first term of 2010 or the last term of 2011 were included. We collected
      patients' baseline characteristics, tumour histology and stage, pemetrexed
      indication and performance status at the start of treatment. In all, 107 and 170
      patients (62 +/- 11 years old) from 17 hospitals were included in 2010 and 2011,
      respectively. The predominant histology was adenocarcinoma (85%), 88% of patients
      had stage IV tumours and 52% Eastern Cooperative Oncology Group stage (ECOG) 1.
      Pemetrexed indications in 2010 and 2011 were: First line combined with platinum
      (28.97-37.64%); first line combined with platinum and maintenance with pemetrexed
      (24.30-28.82%); second line mono-therapy (12.15-7.65%) and maintenance (2.15
      7.05%). Off-label use was detected in 22.43% (2010) and 18.84% (2011). In
      conclusion, pemetrexed combined with platinum is mainly used as first-line
      treatment in NSCLC patients with stage IV, adenocarcinoma histologic subtype and
      good performance status. Off-label use is high (especially in 2010). An adequate
      therapeutic positioning for pemetrexed based on effectiveness and safety analysis
      should be defined, so that NSCLC patients could be beneficiated with the most
      cost-effective chemotherapy treatment.

PMID- 25971604
TI  - A novel 1-Cys thioredoxin peroxidase gene in Apis cerana cerana: characterization
      of AccTpx4 and its role in oxidative stresses.
AB  - Thioredoxin peroxidase (Tpx), also named peroxiredoxin (Prx), is an important
      peroxidase that can protect organisms against stressful environments. AccTpx4, a
      1-Cys thioredoxin peroxidase gene from the Chinese honey bee Apis cerana cerana,
      was cloned and characterized. The AccTpx4 gene encodes a protein that is
      predicted to contain the conserved PVCTTE motif from 1-Cys peroxiredoxin.
      Quantitative real-time PCR (Q-PCR) and Western blotting revealed that AccTpx4 was
      induced by various oxidative stresses, such as cold, heat, insecticides,
      H(2)O(2), and HgCl(2). The in vivo peroxidase activity assay showed that
      recombinant AccTpx4 protein could efficiently degrade H(2)O(2) in the presence of
      DL-dithiothreitol (DTT). In addition, disc fusion assays revealed that AccTpx4
      could function to protect cells against oxidative stresses. These results
      indicate that AccTpx4 plays an important role in oxidative stress responses and
      may contribute to the conservation of honeybees.

PMID- 25971605
TI  - Putaminal alteration in multiple sclerosis patients with spinal cord lesions.
AB  - Typical multiple sclerosis (MS) lesions occur in the brain as well as in the
      spinal cord. However, two extreme magnetic resonance imaging phenotypes appear
      occasionally: those with predominantly spinal cord lesions (MS + SL) and those
      with cerebral lesions and no detectable spinal lesions (MS + CL). We assessed
      whether morphological differences can be found between these two extreme
      phenotypes. We examined 19 patients with MS + SL, 18 with MS + CL and 20
      controls. All subjects were examined using magnetic resonance imaging, including
      anatomical and diffusion tensor imaging sequences. Voxel-based morphologic and
      regions of interest-based analyses and tract-based spatial statistics were
      performed. Patients also underwent neuropsychological testing. Demographic,
      clinical and neuropsychological characteristics did not differ between MS + SL
      and MS + CL patients. Patients with MS + SL showed significantly larger putamen
      volumes than those with MS + CL which correlated negatively with disability.
      Compared to controls, only MS + CL revealed clear cortical and deep gray matter
      atrophy, which correlated with cerebral lesion volume. Additionally, extensive
      white matter microstructural damage was found only in MS + CL compared to MS + SL
      and controls in the tract-based spatial statistics. Higher putamen volumes in MS
      + SL could suggest compensatory mechanisms in this area responsible for motor
      control. Widely reduced fractional anisotropy values in MS + CL were caused by
      higher cerebral lesion volume and thus presumably stronger demyelination, which
      subsequently leads to higher global gray matter atrophy.

PMID- 25971606
TI  - Magnitude and determinants of change in objectively-measured physical activity,
      sedentary time and sleep duration from ages 15 to 17.5y in UK adolescents: the
      ROOTS study.
AB  - BACKGROUND: Self-reported physical activity (PA) and sleep duration (SLP) change
      markedly throughout adolescence. We sought to quantify changes in objectively
      measured PA, sedentary time (ST) and SLP through adolescence, and to investigate
      baseline body composition and baseline activity levels as determinants of change.
      METHODS: Individually calibrated combined heart rate and movement sensing was
      used to estimate PA energy expenditure (PAEE), SLP, daily ST and time in light
      (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous physical activity
      (MVPA) in 144 adolescents (50% boys) of mean age 15.1(+/-0.3)y at baseline and
      17.5(+/-0.3)y at follow-up. Changes in PA (DeltaPA), ST (DeltaST) and SLP
      (DeltaSLP) were calculated as follow-up minus baseline values. Waist
      circumference (WC) was measured at baseline and follow-up, as was fat mass index
      (FMI) and fat-free mass index (FFMI) by a pooled estimation method including bio
      impedance. Comparison of baseline and follow-up activity was made by mixed-model
      ANOVA. Linear regression adjusted for baseline demographics, total and weekend
      hours of monitor wear time and the seasons of activity measurements, was used to
      investigate baseline body composition as determinants of DeltaPA, DeltaST and
      DeltaSLP. A further model adjusted for baseline of the outcome assessed baseline
      activity as a predictor of behaviour change, and investigated associations for
      baseline body composition independent of the baseline level of the outcome.
      RESULTS: From baseline to follow-up levels of MPA and VPA declined (p <= 0.039).
      The annual decline in MVPA was equivalent to -4.5 and -3.0 min/d in boys and
      girls, respectively. Baseline FMI, FFMI and WC were positively associated with
      DeltaLPA and negatively associated with DeltaST in boys when adjusted for
      baseline of the outcome (p <= 0.037 for all). SLP increased from baseline to
      follow-up (p = 0.004) but DeltaSLP was not associated with baseline body
      composition (p >= 0.13). For all variables, higher baseline levels were
      associated with greater declines over time (p <= 0.003). CONCLUSIONS: Levels of
      higher-intensity PA decline from mid-to-late adolescence, whereas the duration of
      sleep increases. Changes in LPA and ST may be associated with baseline body
      composition, but the baseline level of the outcome is consistently the strongest
      predictor of changes in adolescent activity.

PMID- 25971607
TI  - [Watchful waiting vs surgical repair of oligosymptomatic incisional hernias:
      Current status of the AWARE study].
AB  - INTRODUCTION: Incisional hernias are one of the the most frequent complications
      in visceral surgery and incisional hernia repair has a relevant complication
      rate. Therefore, there have to be solid indications before carrying out
      incisional hernia repair. To date, there is a lack of evidence concerning the
      correct indications for surgical repair of incisional hernias. The AWARE trial
      compares watchful waiting to surgical repair of incisional hernias. MATERIAL AND
      METHODS: The AWARE trial is a prospective randomized multicenter trial. Patients
      with asymptomatic or oligosymptomatic incisional hernia are randomized into the
      watchful waiting or the surgical repair group with a follow-up of 2 years. The
      primary endpoint is pain during normal activities due to the hernia or the hernia
      repair after 2 years measured on the hernia-specific surgical pain scale (SPS).
      RESULTS: In this study 36 centers are participating throughout Germany, more than
      1600 patients had been screened up to 31 December 2014 and 234 (14.6%) of the
      screened patients could be recruited. CONCLUSION: The AWARE study will provide
      evidence concerning the two therapeutic options of watchful waiting and surgical
      repair of incisional hernia.

PMID- 25971608
TI  - [The validity of routine data on quality assurance: A qualitative systematic
      review].
AB  - BACKGROUND: The assessment of the quality of medical practice is a legitimate
      requirement by society. Reliable methods for measurement of the quality of
      performance are sought worldwide. Quality is often quantified by using
      administrative data and in Germany this method has been implemented by the health
      insurance company AOK. OBJECTIVES: (1) How is the AOK quality system rated by
      senior consultant surgeons? (2) How valid are quality statements derived from
      administrative data? METHODS: This article was compiled following the PRISMA
      (i.e. preferred reporting items for systematic reviews and meta-analyses)
      statement for qualitative systematic reviews. In order to answer the first
      question the Professional Association of German Surgeons (Berufsverband der
      Deutschen Chirurgen) initiated two surveys and to answer the second question a
      structured literature search following the PICO (i.e. patient problem or
      population, intervention, comparison control or comparator and outcomes) format
      was initiated. In addition numerous websites were contacted. RESULTS: Of the
      responding senior consultant surgeons 95% considered that the AOK method of
      quality measurement by administrative data is not objective. One third was
      definitely wrongly classified. The literature search revealed that no validation
      data exist for the AOK indicators, including the Elixhauser comorbidity risk
      score. Altogether, the sensitivity of indicators is poor when good sensitivity is
      defined by the Institute for Applied Quality Improvement and Research in Health
      Care (AQUA Institute) as >= 80 < 90%. CONCLUSIONS: Quality statements resulting
      from administrative data alone are unreliable.

PMID- 25971609
TI  - [Cystic space-occupying lesion of the mediastinum].

PMID- 25971610
TI  - [Interdisciplinary treatment of extensive chest wall defects due to irradiation].

PMID- 25971611
TI  - [Laparoscopic repair of very large hiatus hernia: Suture versus absorbable and
      nonabsorbable mesh implantation].

PMID- 25971612
TI  - [Transaxillary robot-assisted thyroidectomy: First experiences with a new
      operation technique].
AB  - BACKGROUND: The main advantage of transaxillary robotic-assisted thyroid surgery
      (TRAT) is the avoidance of a scar on the neck. As TRAT is still rarely performed
      in Germany, there are not yet any German reports on acceptance, operation times
      and complications. METHODS: In a pilot study all patients with an indication for
      hemithyroidectomy without preoperative evidence of malignancies or previous neck
      surgery and a lobe size < 30 ml, a body mass index (BMI) < 30 and age > 18 years
      were offered transaxillary robotic-assisted hemithyroidectomy (TRAHT) after a
      detailed explanation of this operation. The acceptance of this new technique, the
      operation time, complications and patient satisfaction were prospectively
      recorded and analyzed. RESULTS: Between January 2013 and October 2014 a total of
      65 patients were offered the option of a TRAHT and 21 (32%) patients opted for
      this surgical technique. None of these 21 operations had to be converted and
      there were no intraoperative complications. The median operation time was 190 min
      (range 106-300 min) with a significant learning curve (first 5 TRAHT 219 min and
      last 5 TRAHT 163 min), 10 (48%) patients had a postoperative slight transient
      skin dysesthesia in the area of the access route, 4 (19%) patients had a
      transient recurrent laryngeal nerve palsy and 2 patients (9%) had a transient
      upper brachial plexus palsy. After the first 21 TRAHT operations, 2 Dunhill
      operations for Grave's disease were also performed via a single axillary
      incision. The operation times were 320 min and 260 min without complications and
      21 out of the 23 patients (91%) were highly satisfied with the cosmetic result
      and would choose TRAT again. CONCLUSION: The TRAT procedure still has low
      acceptance by German patients but patient satisfaction after surgery is high due
      to the cosmetic result. The extended operation time, new complications (e.g.
      transient plexus palsy) and a potentially increased rate of transient recurrent
      laryngeal nerve palsy must be critically considered.

PMID- 25971613
TI  - [The phenomenon of covert self-mutilation in the surgical routine].
AB  - Factitious disorders are conditions which are unknown to many physicians but have
      a prevalence of 1-5 % in outpatient departments and hospitals. In order to avoid
      prolonged and complicated (false) treatment in surgery this article gives a
      review of the definition, epidemiology and pathogenesis of factitious disorders
      as well as clinical symptoms and therapy options. A focus is placed on the
      identification of patients, treatment strategies and the prevention of
      malpractice. Additionally, clinical features of the disorder are illustrated with
      the description of some characteristic cases. 

PMID- 25971614
TI  - Factors associated with fecal incontinence in a nationally representative sample
      of diabetic women.
AB  - INTRODUCTION AND HYPOTHESIS: Fecal incontinence (FI) is a debilitating condition
      that significantly affects quality of life, and has been associated with multiple
      risk factors. Our goal was to assess the prevalence of FI among diabetic women
      and evaluate factors associated with FI in this population. METHODS: The National
      Health and Nutrition Examination Survey (NHANES) from 2005 to 2010 was used to
      evaluate women with diabetes mellitus and FI. FI was defined as involuntary loss
      of mucus, liquid, or solid stool at least monthly. Severity was evaluated using
      the Fecal Incontinence Severity Index. Potential risk factors associated with FI
      were explored with weighted chi-squared statistics. Variables associated with FI
      in multivariable logistic regression analysis are reported with odds ratios (OR)
      and 95 % confidence intervals (95 % CI). RESULTS: Among 7,039 women, 13.6 % were
      diabetic, and 18.1 % of diabetic women reported FI compared to 8.4 % in the
      overall NHANES population (p < .001). In diabetic women, FI was associated with
      advancing age (OR 1.3, 95 % CI 1.1 - 1.5), depression (OR 2.0 95 % CI 0.9 - 4.5),
      poorer health status (OR 1.9, 95 % CI 1.2 - 3.1), urinary incontinence (OR 3.5,
      95 % CI 2.1 - 5.9) and bowel movement frequency of >=21/week (OR 4.9, 95 % CI 2.3
      - 10.6) in a multivariable logistic regression model adjusted for race, education
      level, BMI, comorbidities, prior hysterectomy, and stool consistency.
      CONCLUSIONS: FI affects one in five diabetic women and is strongly associated
      with high bowel movement frequency, a possible important modifiable factor that
      should be investigated further in prospective studies.

PMID- 25971615
TI  - Treatment patterns and survival outcomes in patients with cervical cancer
      complicated by complete uterine prolapse: a systematic review of literature.
AB  - INTRODUCTION AND HYPOTHESIS: Cervical cancer complicated by complete uterine
      prolapse is a rare clinical entity and uniform management recommendations have
      yet to be determined. The aim of the current review was to examine the effects of
      management patterns on survival outcomes in cervical cancer patients with
      complete uterine prolapse. METHODS: A systematic review of the literature was
      conducted using three public search engines. This included case reports with
      detailed descriptions of tumor characteristics, cancer management, and survival
      outcomes. Treatment patterns and tumor characteristics were correlated to
      survival outcomes. RESULTS: There were 78 patients with cervical cancer with
      complete uterine prolapse. Their mean age was 63.7 years. The median duration of
      prolapse was 147.9 months and 22.2% of the patients experienced
      persistent/recurrent prolapse after cancer treatment. The mean tumor size was 8.9
      cm and squamous cell carcinoma (83.9%) was the most common histologic type. The
      majority of patients (56.2%) had stage I cancer. Tumor characteristics were
      similar across the treatment patterns. Survival outcomes were more favorable with
      surgery-based treatment (48 patients) than with radiation-based treatment (30
      patients): 5-year recurrence-free survival rate 72.0% vs. 62.9% (p = 0.057), and
      5-year disease-specific overall survival rate 77.0% vs. 68.2% (p = 0.017). After
      controlling for age and stage, surgery-based therapy remained an independent
      prognostic factor for better disease-specific overall survival outcome (hazard
      ratio 0.32, 95% confidence interval 0.11 - 0.94, adjusted p = 0.039).
      CONCLUSIONS: Although limited in study size, our results at least suggest that
      surgery-based treatment may have a positive effect on survival outcome in
      cervical cancer patients with complete uterine prolapse.

PMID- 25971617
TI  - Palliative sedation, foregoing life-sustaining treatment, and aid-in-dying: what
      is the difference?
AB  - After a review of terminology, I identify-in addition to Margaret Battin's list
      of five primary arguments for and against aid-in-dying-the argument from
      functional equivalence as another primary argument. I introduce a novel way to
      approach this argument based on Bernard Lonergan's generalized empirical method
      (GEM). Then I proceed on the basis of GEM to distinguish palliative sedation,
      palliative sedation to unconsciousness when prognosis is less than two weeks, and
      foregoing life-sustaining treatment from aid-in-dying. I conclude (1) that aid-in
      dying must be justified on its own merits and not on the basis of these well
      established palliative care practices; and (2) that societies must decide, in
      weighing the merits of aid-in-dying, whether or not to make the judgment that no
      life is better than life-like-this (however this is specified) part of their
      operative value structure.

PMID- 25971618
TI  - Genetics of diabetic nephropathy: a long road of discovery.
AB  - The global prevalence of diabetic nephropathy is rising in parallel with the
      increasing incidence of diabetes in most countries. Unfortunately, up to 40 % of
      persons diagnosed with diabetes may develop kidney complications. Diabetic
      nephropathy is associated with substantially increased risks of cardiovascular
      disease and premature mortality. An inherited susceptibility to diabetic
      nephropathy exists, and progress is being made unravelling the genetic basis for
      nephropathy thanks to international research collaborations, shared biological
      resources and new analytical approaches. Multiple epidemiological studies have
      highlighted the clinical heterogeneity of nephropathy and the need for better
      phenotyping to help define important subgroups for analysis and increase the
      power of genetic studies. Collaborative genome-wide association studies for
      nephropathy have reported unique genes, highlighted novel biological pathways and
      suggested new disease mechanisms, but progress towards clinically relevant risk
      prediction models for diabetic nephropathy has been slow. This review summarises
      the current status, recent developments and ongoing challenges elucidating the
      genetics of diabetic nephropathy. 

PMID- 25971619
TI  - Update on glycemic control for the treatment of diabetic kidney disease.
AB  - Diabetic kidney disease (DKD) is a common, complex condition that has become a
      significant public health problem. The beneficial effects of intensive glycemic
      control in type 1 diabetes mellitus on development of DKD are proven; however,
      the evidence for nephroprotection in patients with type 2 diabetes is
      conflicting. Moreover, a strategy of intensive glycemic control increases the
      risk for adverse effects (hypoglycemic episodes) with no obvious impact on
      macrovascular events or mortality in recent large randomized controlled trials.
      The risk for hypoglycemia with intensive therapy is heightened in patients with
      significant renal dysfunction, due to decreased renal clearance of insulin.
      Establishing an ideal level of glycemic control in patients requires an
      individualized approach taking into account duration of diabetes and presence of
      coexisting comorbidities and pre-existing DKD. In this article, we review the
      available evidence from both observational studies and randomized controlled
      trials and provide suggestions about evaluating the potential benefits and harm
      from intensive glycemic control in patients. We also discuss how in the future, a
      personalized approach using biomarkers might help identify patients most likely
      to respond as well as those most susceptible to harm. We believe that using the
      optimal level of glycemic control in diabetic patients using a multi-pronged
      strategy will improve individual patient outcomes and decrease the overall burden
      of morbidity and mortality. 

PMID- 25971620
TI  - Intra-observer and inter-observer errors in CT measurement of torsional profiles
      of lower limbs: a retrospective comparative study.
AB  - BACKGROUND: The purpose of this study was to determine errors in measurement of
      torsional profiles (TP) (torsional femoral angle, torsional tibial angle, and
      femoral ankle angle) among four orthopedic surgeons, experts, and non-experts in
      measurement, and the learning curve. METHODS: Twenty-six lower extremities of 13
      patients with spastic diplegia candidates for femoral/tibial derotational
      osteotomy had preoperative bilateral computer tomography (CT) scan grams to
      establish the TP. Each measurement was done by four orthopedic surgeons, two
      experienced clinicians and interpreters of CT imaging and two with limited
      clinical and imaging assessment experiences. Images were blinded and the surgeons
      made three determinations at least 5 days apart; the three angles were measured
      each time for each limb. Intra-observer and inter-observer variability were
      determined using bias, standard deviation, and interclass correlation
      coefficient. RESULTS: Significant inter-observer variability and bias were noted
      between experts and non-experts (average variability: ICC experts: 0.88 +/- 0.15;
      ICC non-experts: 0.91 +/- 0.09). For non-experts, excessive bias (25 degrees  and
      14 degrees ) was observed. An associated improvement in bias with additional
      measurement experience indicated a potential significant learning curve for
      interpreting these studies. Less inter-observer variability was observed between
      experts. CONCLUSIONS: Measurement of TP is a reliable tool when used by
      experienced personnel, and their use as a preoperative tool should be reserved to
      ones with experience with such image assessments. Non-experts' measurements
      produced a weak agreement when compared to experts'.

PMID- 25971621
TI  - Editing the genome to introduce a beneficial naturally occurring mutation
      associated with increased fetal globin.
AB  - Genetic disorders resulting from defects in the adult globin genes are among the
      most common inherited diseases. Symptoms worsen from birth as fetal gamma-globin
      expression is silenced. Genome editing could permit the introduction of
      beneficial single-nucleotide variants to ameliorate symptoms. Here, as proof of
      concept, we introduce the naturally occurring Hereditary Persistance of Fetal
      Haemoglobin (HPFH) -175T>C point mutation associated with elevated fetal gamma
      globin into erythroid cell lines. We show that this mutation increases fetal
      globin expression through de novo recruitment of the activator TAL1 to promote
      chromatin looping of distal enhancers to the modified gamma-globin promoter. 

PMID- 25971622
TI  - Integrin-beta1, not integrin-beta5, mediates osteoblastic differentiation and ECM
      formation promoted by mechanical tensile strain.
AB  - BACKGROUND: Mechanical strain plays a great role in growth and differentiation of
      osteoblast. A previous study indicated that integrin-beta (beta1, beta5) mediated
      osteoblast proliferation promoted by mechanical tensile strain. However, the
      involvement of integrin-beta in osteoblastic differentiation and extracellular
      matrix (ECM) formation induced by mechanical tensile strain, remains unclear.
      RESULTS: After transfection with integrin-beta1 siRNA or integrin-beta5 siRNA,
      mouse MC3T3-E1 preosteoblasts were cultured in cell culture dishes and stimulated
      with mechanical tensile strain of 2500 microstrain (MUepsilon) at 0.5 Hz applied
      once a day for 1 h over 3 or 5 consecutive days. The cyclic tensile strain
      promoted osteoblastic differentiation of MC3T3-E1 cells. Transfection with
      integrin-beta1 siRNA attenuated the osteoblastic diffenentiation induced by the
      tensile strain. By contrast, transfection with integrin-beta5 siRNA had little
      effect on the osteoblastic differentiation induced by the strain. At the same
      time, the result of ECM formation promoted by the strain, was similar to the
      osteoblastic differentiation. CONCLUSION: Integrin-beta1 mediates osteoblast
      differentiation and osteoblastic ECM formation promoted by cyclic tensile strain,
      and integrin-beta5 is not involved in the osteoblasts response to the tensile
      strain.

PMID- 25971623
TI  - Enhancement of experimental cutaneous leishmaniasis by Leishmania extract:
      identification of a disease-associated antibody specificity.
AB  - BACKGROUND: Both Leishmania braziliensis and Leishmania amazonensis induce
      cutaneous disease when injected in the skin of BALB/c mice. However, L.
      amazonensis may also visceralize in that strain of mice, infecting mainly the
      liver and spleen. In addition, whereas BALB/c mice die with a progressive
      cutaneous disease when infected by L. amazonensis, the infection by L.
      braziliensis is spontaneously cured. In a previous work, we have found that
      intravenous injections of L. amazonensis amastigote extract (LaE) potentiated a
      L. braziliensis infection in BALB/c mice, and that this infection-promoting
      activity could be inhibited by the addition of protease inhibitors to the
      extract. METHODS: In order to detect markers of disease evolution, in the present
      work we analyzed the specificity of the anti-L. amazonensis antibody response of
      L. braziliensis-infected BALB/c mice injected intravenously with saline or LaE,
      supplemented or not with protease inhibitors, by the Western blot technique.
      RESULTS: IgG1 antibodies recognizing an antigen with apparent molecular weight of
      116 kDa were specifically detected in BALB/c mice that had been turned
      susceptible to L. braziliensis infection by injections of LaE. CONCLUSION: A Th2
      immune response (IgG1 antibody-producing) against this 116 kDa antigen,
      therefore, could be associated with susceptibility to severe Leishmania
      infection.

PMID- 25971624
TI  - Development of second primary malignancy in patients with non-Hodgkin lymphoma: a
      nationwide population-based study.
AB  - BACKGROUND: With the improved survival of non-Hodgkin lymphoma (NHL) patients,
      development of second primary malignancy (SPM) has become an increasingly
      important issue in these long-term survivors. METHODS: We conducted a
      retrospective study to analyze NHL patients diagnosed between January 1997 and
      December 2010 in Taiwan. Standardized incidence ratios (SIRs) were applied to
      compare the risk of SPMs in NHL patients and the general population. Multivariate
      analysis was performed to determine the independent predictors of SPM. RESULT:
      NHL patients have a significantly greater risk of developing SPM [SIR 1.43; 95 %
      confidence interval (CI) 1.32-1.55; p < 0.001). A significantly high SIR was
      noted for leukemia, myeloma, and neoplasms of the bone and soft tissue, thyroid,
      central nervous system, skin, stomach, head and neck, liver and biliary tract,
      and the lungs and mediastinum. Multivariate analysis revealed that age >=60 years
      [hazard ratios (HR) 2.04], being male (HR 1.22), comorbidities of chronic
      obstructive pulmonary disease (HR 1.34), liver cirrhosis (HR 1.50), hepatitis C
      infection (HR 1.94) and therapy containing radiotherapy (HR 1.38) were the
      significant predictors for SPM occurrence. The median follow-up time and survival
      time were 3.37 and 9.45 years, respectively. CONCLUSION: This Taiwanese
      population-based study provides updated data about the risk of SPM in NHL
      patients, demonstrating an approximately 1.5 time greater risk of SPM compared to
      the general population. A high risk of SPM for myeloma and hepatocellular
      carcinoma is unique to Asian patients.

PMID- 25971625
TI  - Evaluation of BRCA1/2 mutational status among German and Austrian women with
      triple-negative breast cancer.
AB  - PURPOSE: Testing for BRCA1 and BRCA2 mutations in breast cancer patients is used
      to identify the risk of second primary cancers and the risk of cancer in the
      patients' family. Women with triple-negative breast cancer (TNBC) are thought to
      be more likely to be BRCA1/2 mutation carriers, but most national guidelines for
      genetic testing, including those used in Germany and Austria, do not consider
      receptor triple negativity. METHODS: We determined the prevalence of BRCA1 and
      BRCA2 mutations within a cohort of 100 unselected TNBC cases, including patients
      from Germany and Austria to identify those BRCA-positive patients with a masked
      family history and who would have been missed due to respective current national
      guidelines. Double-stranded Sanger sequencing of all exons of BRCA1 and BRCA2,
      respectively, was performed. RESULTS: We identified a total of 13 deleterious
      mutations in BRCA1 and a total of four deleterious mutations in BRCA2. The total
      rate of deleterious BRCA1/2 mutation carriers was 21 % in our cohort. Six novel
      mutations, including two deleterious mutations, have been identified, which have
      not been described in public mutation databases so far. According to current
      German and Austrian national guidelines for genetic testing, 38.1 and 52.4 %,
      respectively, of BRCA1/2 mutation carriers would have been overlooked.
      CONCLUSIONS: We conclude that the prevalence of BRCA1 and BRCA2 mutations is high
      in TNBC patients and that BRCA1/2 mutations are not restricted to young women or
      patients with a positive family history. Receptor triple negativity should
      therefore be considered in BRCA1/2 genetic testing guidelines.

PMID- 25971627
TI  - Singlet and triplet excitons and charge polarons in cycloparaphenylenes: a
      density functional theory study.
AB  - The conformational structure and the electronic properties of various electronic
      excitations in cycloparaphenylenes (CPPs) are calculated using hybrid density
      functional theory (DFT). The results demonstrate that wavefunctions of singlet
      and triplet excitons as well as the positive and negative polarons remain fully
      delocalized in CPPs. In contrast, these excitations in larger CPP molecules
      become localized on several phenyl rings, which are locally planarized, while the
      undeformed ground state geometry is preserved on the rest of the hoop. As
      evidenced by the measurements of bond-length alternation and dihedral angles,
      localized regions show stronger hybridization between neighboring bonds and thus
      enhanced electronic communication. This effect is even more significant in the
      smaller hoops, where phenyl rings have strong quinoid character in the ground
      state. Thus, upon excitation, electron-phonon coupling leads to the self-trapping
      of the electronic wavefunction and release of energy from fractions of an eV up
      to two eVs, depending on the type of excitation and the size of the hoop. The
      impact of such localization on electronic and optical properties of CPPs is
      systematically investigated and compared with the available experimental
      measurements. 

PMID- 25971626
TI  - Sympathotomy for palmar hyperhidrosis: the cutting versus clamping methods.
AB  - PURPOSE: Endoscopic thoracic sympathectomy/sympathotomy for the treatment of
      palmar hyperhidrosis is generally performed by either cutting or clamping the
      sympathetic chain. However, it remains unclear as to which of these methods is
      more effective and has fewer side effects. This study was conducted to compare
      the effects of sympathotomy by cutting or clamping at T3 on two outcomes-
      postoperative palmar sweating and compensatory sweating; it also evaluated
      postoperative patient satisfaction. METHODS: The participants were among 289
      patients who underwent bilateral sympathotomy at T3 for palmar hyperhidrosis.
      These patients were sent questionnaires by mail to assess their self-reported
      degree of postoperative palmar sweating and compensatory sweating, as well as
      their level of satisfaction. Of the 92 patients who responded to the
      questionnaire, 54 had undergone sympathotomy by cutting (cutting group) and 38 by
      clamping (clamping group). RESULTS: The degree of postoperative palmar sweating
      was significantly lower in the cutting group than in the clamping group. However,
      compensatory sweating was significantly more severe in the cutting group than in
      the clamping group. No significant difference was observed in the degree of
      patient satisfaction between the groups. CONCLUSIONS: Sympathotomy by clamping at
      T3 was less effective in reducing the primary symptom of postoperative palmar
      sweating, but induced less compensatory sweating than did sympathotomy by cutting
      at T3. However, both methods were similar with regard to patient satisfaction.
      The degree of postoperative palmar sweating and the severity of compensatory
      sweating were inversely correlated with the degree of patient satisfaction.

PMID- 25971628
TI  - Relationship between maternal gestational hypertension and home blood pressure in
      7-year-old children and their mothers: Tohoku Study of Child Development.
AB  - Women who had hypertensive disorders in pregnancy have an increased risk of
      cardiovascular diseases in later life. No studies, however, have investigated
      whether maternal hypertensive disorders in pregnancy affect self-measured blood
      pressure at home (HBP) in mothers and their children. We evaluated the
      association between maternal hypertension during pregnancy and HBP based on the
      prospective Tohoku Study of Child Development birth cohort study, which was
      performed in two areas in Japan. We included children in a singleton birth at
      term (36-42 weeks of gestation) with a birth weight of >2400 g. We collected
      prenatal care data from the medical charts. Because only two mothers experienced
      preeclampsia, we defined gestational hypertension (GH) as a hypertensive disorder
      in pregnancy. Seven years after birth, mothers and their children measured their
      HBP in the morning for 2 weeks. Of 813 eligible mothers, 28 (3.4%) experienced
      GH, and those were of a similar age compared with 785 non-GH mothers (37.3 vs.
      38.0 years; P=0.41). Women with GH had higher body mass index (BMI) (23.8 vs.
      21.4 kg m(-)(2); P=0.01) and elevated HBP (120.3/76.8 vs. 110.4/68.6 mm Hg;
      P<0.0002) 7 years after delivery. However, HBP was similar in children with and
      without GH mothers (93.5/55.9 vs. 94.1/56.1 mm Hg, P>0.38). These results were
      confirmatory in case-control (1:2) analyses with matching by maternal age,
      maternal BMI before pregnancy, survey area and parity. In conclusion, maternal GH
      did not affect HBP in offspring but strongly affected maternal HBP even 7 years
      after birth.

PMID- 25971631
TI  - The effect of anchoring on the nematic flow in channels.
AB  - Understanding the flow of liquid crystals in microfluidic environments plays an
      important role in many fields, including device design and microbiology. We
      perform hybrid lattice-Boltzmann simulations of a nematic liquid crystal flowing
      under an applied pressure gradient in two-dimensional channels with various
      anchoring boundary conditions at the substrate walls. We investigate the
      relationship between the flow rate and the pressure gradient and the
      corresponding profile of the nematic director, and find significant departures
      from the linear Poiseuille relationship. We also identify a morphological
      transition in the director profile and explain this in terms of an instability in
      the dynamical equations. We examine the qualitative and quantitative effects of
      changing the type and strength of the anchoring. Understanding such effects may
      provide a useful means of quantifying the anchoring of a substrate by measuring
      its flow properties. 

PMID- 25971629
TI  - Carotid intima-media thickness and elastic properties of aortas in normotensive
      children of hypertensive parents.
AB  - A significant correlation between hypertension history and high blood pressure
      has been observed with regard to age, race and gender. Investigating carotid
      intima-media thickness and aortic stiffness prior to the development of
      hypertension in children of hypertensive parents enabled us to evaluate these
      patients for subclinical atherosclerosis. We compared carotid intima-media
      thickness, aortic strain, distensibility, stiffness indices and elastic modulus
      in 67 normotensive children whose parents had a diagnosis of essential
      hypertension and 39 normotensive children with no parental history of
      hypertension. Although there were no significant differences between the two
      groups in terms of systolic blood pressure, diastolic blood pressure, average
      blood pressure and pulse pressure (P>0.05), systolic blood pressures were higher
      among patients 15 years and older in the study group. No significant differences
      were noted between the control and study groups regarding interventricular septal
      thickness, left-ventricular posterior wall thickness, left-ventricular systolic
      and diastolic diameter and aortic annulus diameter (P>0.05). The left atrium
      diameter was larger in the study group compared with that in the control group,
      mainly because of the values of the 15-year-old and older children (P=0.01). The
      mean, maximum and minimum values of carotid intima-media thickness were
      significantly different in the study group compared with the control group among
      all age groups (P<0.001, P<0.001, P=0.006, respectively). Aortic systolic and
      diastolic diameters were larger in normotensive children of hypertensive parents
      compared with the control group (P=0.014, P=0.001, respectively). Although there
      were no differences between the study and control groups regarding aortic strain,
      aortic distensibility, elastic modulus and stiffness indices (P>0.05), aortic
      distensibility was lower, and aortic stiffness indices were higher among children
      15 years and older in the study group. An increase in the carotid intima-media
      thickness in all age groups and a decrease in aortic elastic properties in 15
      year-old and older children of hypertensive parents may indicate subclinical
      atherosclerosis in these apparently healthy children. 

PMID- 25971630
TI  - CCL5 upregulates IL-10 expression and partially mediates the antihypertensive
      effects of IL-10 in the vascular smooth muscle cells of spontaneously
      hypertensive rats.
AB  - Interleukin (IL)-10 inhibits angiotensin (Ang) II-induced vascular dysfunction
      and reduces blood pressure in hypertensive pregnant rats. The chemokine CCL5 has
      also been shown to downregulate Ang II-induced hypertensive mediators in
      spontaneously hypertensive rats (SHRs). This study investigated the effects of
      CCL5 on IL-10 expression, as well as its mechanisms of action in the vascular
      smooth muscle cells (VSMCs) of SHRs. CCL5 increased IL-10 expression in the VSMCs
      of SHRs; the s.c. injection of CCL5 (1.5 MUg kg(-1), twice a day) for 3 weeks
      into SHRs with established hypertension upregulated IL-10 expression in both the
      thoracic aorta and the VSMCs and decreased systolic blood pressure. CCL5-induced
      the elevation of IL-10 expression, an effect mediated primarily via the
      activation of an Ang II subtype II receptor (AT2 R). Dimethylarginine
      dimethylaminohydrolase (DDAH)-1 activity also contributed to the elevation of IL
      10 expression via CCL5 in the VSMCs of SHRs. Moreover, CCL5 partially mediated
      the inhibitory effects of IL-10 on Ang II-induced 12-lipoxygenase (LO) and
      endothelin (ET)-1 expression in the VSMCs of SHRs. Taken together, this study
      provides novel evidence that CCL5 plays a role in the upregulation of IL-10
      activity in the VSMCs of SHRs.

PMID- 25971632
TI  - Special section featuring selected articles from breath analysis 2014 (6-9 July
      2014, Torun, Poland).

PMID- 25971633
TI  - Amyloid-beta and alpha-synuclein cerebrospinal fluid biomarkers and cognition in
      early Parkinson's disease.
AB  - INTRODUCTION: Cognitive impairment in early Parkinson's disease (PD) is common
      and distinct from early Alzheimer's disease. Predictors and mechanisms are only
      partially known, but alpha-synuclein, amyloid-beta and tau dysmetabolism may be
      involved. Our aim was to study associations between cerebrospinal fluid
      biomarkers (CSF) and cognition in non-dementia PD compared to normal controls
      (NC) and non-PD patients with mild cognitive impairment (MCI non-PD). METHODS:
      Patients were classified as having normal, subjective or mild cognitive
      impairment after cognitive screening. CSF levels of total alpha-synuclein (t
      alpha-syn), amyloid-beta (Abeta) 38, 40 and 42, total tau (T-tau) and
      phosphorylated tau (P-tau) were measured in 34 NC, 31 early, non-dementia PD and
      28 MCI non-PD patients. A well validated neuropsychological test battery was
      administered. RESULTS: In the PD group, 13 had normal cognition, 4 had subjective
      and 14 mild cognitive impairment. PD patients had significantly lower CSF
      biomarker levels of t-alpha-syn, Abeta38, 40 and 42, T-tau and P-tau compared to
      NC. Compared to MCI non-PD, t-alpha-syn, Abeta38 and 40, T-tau and P-tau were
      also lower, while Abeta42 was significantly higher in the PD group. Abeta38 and
      40 correlated strongly with t-alpha-syn levels in PD. Lower Abeta42 was
      associated with decreased verbal learning, delayed verbal recall and response
      inhibition in PD. CONCLUSION: While Abeta38, 40 and t-alpha-syn levels are
      strongly correlated, only lower Abeta42 was associated with reduced cognitive
      functions in early PD, mainly connected to medial temporal lobe-based cognitive
      functions.

PMID- 25971634
TI  - A tribute to Mario Molina.

PMID- 25971636
TI  - What can be done about the increasing prevalence of low back pain and associated
      comorbid factors?

PMID- 25971637
TI  - Pain intervention for older adults: maximizing effectiveness.

PMID- 25971638
TI  - Nonsinogenic facial pain and the role of the sino-nasal outcome test.

PMID- 25971639
TI  - Injury-related synaptic plasticity for the treatment of chronic pain: a new
      approach?

PMID- 25971640
TI  - Management of acute pain in patients on treatment with opioids.
AB  - The use of opioids for both benign and cancer-related chronic pain has increased
      exponentially over the last few years. For this reason, increasing numbers of
      such patients are presenting for surgery. It is known that continuous use of
      opioids is associated with an increase in postoperative analgesic requirements.
      This is believed to be mediated by the development of tolerance and opioid
      induced hyperalgesia. Patients treated with opioids have special needs in the
      perioperative setting and it is the anesthesiologist's responsibility to manage
      these needs optimally. The aim of the present paper is to briefly orient the
      reader in the management of postoperative pain in patients chronically treated
      with licit opioids.

PMID- 25971641
TI  - Intrathecal drug delivery for pain: a clinical guide and future directions.
AB  - Intrathecal infusion of medications allows for a direct delivery of agents to the
      receptors in which they act. This method of treatment is indicated in severe
      chronic pain of cancer or noncancer origin. In recent years, the use of these
      devices has increased and the general pain physician, referring doctor and
      concerned parties such as insurers, needs a better understanding of safety and
      efficacy. This article is an overview of this therapeutic option and also
      provides an update on new innovations and forward thinking approaches at
      improving patient selection and appropriateness of use.

PMID- 25971642
TI  - Best multimodal analgesic protocol for total knee arthroplasty.
AB  - Total knee arthroplasty is one of the most commonly performed operations in the
      USA. As with any elective joint surgery, the primary goal includes functional
      restoration that is not limited by pain. The use of peripheral nerve blocks for
      patients undergoing knee arthroplasty has resulted in decreased pain scores,
      improved early ambulation and decreased time to achieve hospital discharge
      criteria. Concern has been raised over the potential risks of femoral nerve
      block, and there has been growing support for the adductor canal block. It is the
      author's opinion that when not contraindicated, intraoperative neuraxial
      anesthesia combined with a continuous adductor canal block and a multimodal
      medication regimen for postoperative pain control is the best analgesic protocol
      for knee arthroplasty.

PMID- 25971643
TI  - The promise and challenge of virtual gaming technologies for chronic pain: the
      case of graded exposure for low back pain.
AB  - Virtual reality (VR) technologies have been successfully applied to acute pain
      interventions and recent reviews have suggested their potential utility in
      chronic pain. The current review highlights the specific relevance of VR
      interactive gaming technologies for pain-specific intervention, including their
      current use across a variety of physical conditions. Using the example of graded
      exposure treatment for pain-related fear and disability in chronic low back pain,
      we discuss ways that VR gaming can be harnessed to optimize existing chronic pain
      therapies and examine the potential limitations of traditional VR interfaces in
      the context of chronic pain. We conclude by discussing directions for future
      research on VR-mediated applications in chronic pain.

PMID- 25971644
TI  - Future implications of eHealth interventions for chronic pain management in
      underserved populations.
AB  - Many underserved communities, especially those in rural settings, face unique
      challenges that make high quality healthcare less accessible. The implementation
      of eHealth technologies has become a potentially valuable option to disseminate
      interventions. The authors' work in rural Alabama Federally Qualified Health
      Centers provide insights into the access to technology as well as the likelihood
      of utilizing eHealth technology in underserved communities. This paper will
      review current challenges related to digital dissemination of behavioral health
      interventions for chronic pain. Two major concerns are the lack of technological
      resources and the lack of appropriate materials for patients who may have low
      levels of reading, health and/or digital literacy. We will propose some
      recommendations to address common barriers faced by those providing care.

PMID- 25971645
TI  - Environmental impact assessment as a complement of life cycle assessment. Case
      study: Upgrading of biogas.
AB  - This work presents a comparison between an environmental impact assessment (EIA)
      and a life cycle assessment (LCA) using a case study: upgrading of biogas. The
      upgrading of biogas is studied using three solvents: water, physical solvent and
      amine. The EIA follows the requirements of the legislation of Santa Fe Province
      (Argentina), and the LCA follows ISO 14040. The LCA results showed that water
      produces a minor impact in most of the considered categories whereas the high
      impact in the process with amines is the result of its high energy consumptions.
      The positive results obtained in the EIA (mainly associated with the cultural and
      socioeconomic components) make the project feasible and all the negative impacts
      can be mitigated by preventive and remedial measures. From the strengths and
      weaknesses of each tool, it is inferred that the EIA is a procedure that can
      complement the LCA. 

PMID- 25971646
TI  - FISHing Tips: What Every Clinician Should Know About 1p19q Analysis in Gliomas
      Using Fluorescence in situ Hybridisation.
AB  - 1p19q co-deletion is a chromosomal alteration associated with primary brain
      tumours of oligodendroglial histology. It is an established predictive and
      prognostic biomarker that informs whether patients are offered radiotherapy,
      chemotherapy or both. In the near future, 1p19q co-deletion status may also be
      incorporated into the reclassification of gliomas. Analysis is commonly carried
      out using fluorescence in situ hybridisation (FISH) because it is a reliable and
      validated laboratory technique. The result is generally considered to be
      dichotomous (1p19q co-deletion present or absent), but there are subtleties in
      interpretation that are of clinical relevance. Separate centres may interpret
      certain chromosome deletion patterns differently. Pivotal trials in mixed and
      pure anaplastic oligodendrogliomas have used slightly different FISH probe ratios
      as the cut-off for chromosome deletion. Here we review the clinical implications
      of this variability and review the process of 1p19q co-deletion assessment using
      FISH in gliomas from a clinician's perspective. We also consider common
      alternative methods of analysis. 

PMID- 25971647
TI  - Adverse effects of glucocorticoids: coagulopathy.
AB  - Hypercortisolism is associated with various systemic manifestations, including
      central obesity, arterial hypertension, glucose intolerance/diabetes mellitus,
      dyslipidemia, nephrolithiasis, osteoporosis, gonadal dysfunction, susceptibility
      to infections, psychiatric disorders, and hypercoagulability. The activation of
      the hemostatic system contributes to the development of atherosclerosis and
      subsequent cardiovascular morbidity and mortality. Previous studies have
      identified an increased risk of both unprovoked and postoperative thromboembolic
      events in patients with endogenous and exogenous Cushing's syndrome (CS). The
      risk for postoperative venous thromboembolism in endogenous CS is comparable to
      the risk after total hip or knee replacement under short-term prophylaxis. The
      mechanisms that are involved in the thromboembolic complications in
      hypercortisolism include endothelial dysfunction, hypercoagulability, and stasis
      (Virchow's triad). It seems that at least two factors from Virchow's triad must
      be present for the occurrence of a thrombotic event in these patients. Most
      studies have demonstrated that this hypercoagulable state is explained by
      increased levels of procoagulant factors, mainly factors VIII, IX, and von
      Willebrand factor, and also by an impaired fibrinolytic capacity, which mainly
      results from an elevation in plasminogen activator inhibitor 1. Consequently,
      there is a shortening of activated partial thromboplastin time and increased
      thrombin generation. For these reasons, anticoagulant prophylaxis might be
      considered in patients with CS whenever they have concomitant prothrombotic risk
      factors. However, multicenter studies are needed to determine which patients will
      benefit from anticoagulant therapy and the dose and time of anticoagulation. 

PMID- 25971648
TI  - Multiple aberrant hormone receptors in Cushing's syndrome.
AB  - The mechanisms regulating cortisol production when ACTH of pituitary origin is
      suppressed in primary adrenal causes of Cushing's syndrome (CS) include diverse
      genetic and molecular mechanisms. These can lead either to constitutive
      activation of the cAMP system and steroidogenesis or to its regulation exerted by
      the aberrant adrenal expression of several hormone receptors, particularly G
      protein coupled hormone receptors (GPCR) and their ligands. Screening for
      aberrant expression of GPCR in bilateral macronodular adrenal hyperplasia (BMAH)
      and unilateral adrenal tumors of patients with overt or subclinical CS
      demonstrates the frequent co-expression of several receptors. Aberrant hormone
      receptors can also exert their activity by regulating the paracrine secretion of
      ACTH or other ligands for those receptors in BMAH or unilateral tumors. The
      aberrant expression of hormone receptors is not limited to adrenal CS but can be
      implicated in other endocrine tumors including primary aldosteronism and
      Cushing's disease. Targeted therapies to block the aberrant receptors or their
      ligands could become useful in the future. 

PMID- 25971650
TI  - Electrothermal Vaporization Sample Introduction for Spaceflight Water Quality
      Monitoring via Gas Chromatography-Differential Mobility Spectrometry.
AB  - In the history of manned spaceflight, environmental monitoring has relied heavily
      on archival sampling. However, with the construction of the International Space
      Station (ISS) and the subsequent extension in mission duration up to one year, an
      enhanced, real-time method for environmental monitoring is necessary. The station
      air is currently monitored for trace volatile organic compounds (VOCs) using gas
      chromatography-differential mobility spectrometry (GC-DMS) via the Air Quality
      Monitor (AQM), while water is analyzed to measure total organic carbon and
      biocide concentrations using the Total Organic Carbon Analyzer (TOCA) and the
      Colorimetric Water Quality Monitoring Kit (CWQMK), respectively. As mission
      scenarios extend beyond low Earth orbit, a convergence in analytical
      instrumentation to analyze both air and water samples is highly desirable. Since
      the AQM currently provides quantitative, compound-specific information for air
      samples and many of the targets in air are also common to water, this platform is
      a logical starting point for developing a multimatrix monitor. Here, we report on
      the interfacing of an electrothermal vaporization (ETV) sample introduction unit
      with a ground-based AQM for monitoring target analytes in water. The results show
      that each of the compounds tested from water have similar GC-DMS parameters as
      the compounds tested in air. Moreover, the ETV enabled AQM detection of
      dimethlsilanediol (DMSD), a compound whose analysis had proven challenging using
      other sample introduction methods. Analysis of authentic ISS water samples using
      the ETV-AQM showed that DMSD could be successfully quantified, while the
      concentrations obtained for the other compounds also agreed well with laboratory
      results. 

PMID- 25971651
TI  - Molecular detection of Neospora caninum in house sparrows (Passer domesticus) in
      Iran.
AB  - Neospora caninum is an intracellular protozoan parasite with a wide range of
      intermediate bird hosts. There is little information describing the prevalence
      and genetic characterization of N. caninum in bird hosts worldwide and in Iran.
      In this study, a total of 217 brain samples of house sparrow (Passer domesticus)
      were examined for N. caninum presence by nested polymerase chain reaction
      targeting the Nc-5 gene. N. caninum DNA was detected in 3.68% (8/217) of
      sparrows. Sequencing of the Nc5 genomic DNA revealed 97-99% of similarity with N.
      caninum sequences deposited in Genbank. To our knowledge, this study is the first
      molecular evidence of N. caninum DNA in bird hosts in Iran. The results of this
      study highlight the role of the house sparrow (Passer domesticus) in maintaining
      and spreading N. caninum infection to canines in the feral and domestic
      environment. 

PMID- 25971652
TI  - Hip Arthroscopy in High-Level Baseball Players.
AB  - PURPOSE: To report the results of hip arthroscopy among high-level baseball
      players as recorded by outcome scores and return to baseball. METHODS: All
      patients undergoing hip arthroscopy were prospectively assessed with the modified
      Harris Hip Score. On review of all procedures performed over a 12-year period, 44
      hips were identified among 41 intercollegiate or professional baseball players
      who had achieved 2-year follow-up. RESULTS: Among the 41 players, follow-up
      averaged 45 months (range, 24 to 120 months), with a mean age of 23 years (range,
      18 to 34 years). There were 23 collegiate (1 bilateral) and 18 professional (2
      bilateral) baseball players, including 10 Major League Baseball players. Of the 8
      Major League Baseball pitchers, 6 (75%) also underwent ulnar collateral ligament
      elbow surgery. Improvement in the modified Harris Hip Score averaged 13 points
      (from 81 points preoperatively to 94 points postoperatively); a paired-samples t
      test determined that this mean improvement of 13 points was statistically
      significant (P < .001). Players returned to baseball after 42 of 44 procedures
      (95%) at a mean of 4.3 months (range, 3 to 8 months), with 90% regaining the
      ability to participate at their previous level of competition. There were no
      complications. Three players (1 bilateral) underwent repeat arthroscopy.
      CONCLUSIONS: This study supports the idea that arthroscopic treatment for a
      variety of hip pathologies in high-level baseball players provides a successful
      return to sport and improvement in functional outcome scores. LEVEL OF EVIDENCE:
      Level IV, therapeutic case series.

PMID- 25971653
TI  - Spin-reconstructed proton-coupled electron transfer in a ferrocene
      nickeladithiolene hybrid.
AB  - A proton-electron dual-responsive system based on a hybrid of ferrocene and
      metalladithiolene (1) was developed. The formation of the dithiafulvenium moiety
      was driven by protonation of the metalladithiolene unit of 1 and by oxidation.
      The change in the electronic structure caused by the protonation was combined
      with the redox properties of the two components of 1, generating two radical
      species with different spin density distributions (3d spin and pi spin).
      Furthermore, a spin-reconstructed proton-coupled electron transfer, i.e., the
      transformation from 3d spin to pi spin accompanied by deprotonation, was achieved
      by a temperature change, the third external stimulus. 

PMID- 25971654
TI  - Orthopaedic surgery in natural disaster and conflict settings: how can quality
      care be ensured?
AB  - PURPOSE: Medecins sans Frontieres (MSF) is one of the main providers of
      orthopaedic surgery in natural disaster and conflict settings and strictly
      imposes a minimum set of context-specific standards before any surgery can be
      performed. Based on MSF's experience of performing orthopaedic surgery in a
      number of such settings, we describe: (a) whether it was possible to implement
      the minimum standards for one of the more rigorous orthopaedic procedures-
      internal fixation--and when possible, the time frame, (b) the volume and type of
      interventions performed and (c) the intra-operative mortality rates and
      postoperative infection rates. METHODS: We conducted a retrospective review of
      routine programme data collected between 2007 and 2014 from three MSF emergency
      surgical interventions in Haiti (following the 2010 earthquake) and three ongoing
      MSF projects in Kunduz (Afghanistan), Masisi (Democratic Republic of the Congo)
      and Tabarre (Haiti). RESULTS: The minimum standards for internal fixation were
      achieved in one emergency intervention site in Haiti, and in Kunduz and Tabarre,
      taking up to 18 months to implement in Kunduz. All sites achieved the minimum
      standards to perform amputations, reductions and external fixations, with a total
      of 9,409 orthopaedic procedures performed during the study period. Intraoperative
      mortality rates ranged from 0.6 to 1.9 % and postoperative infection rates from
      2.4 to 3.5 %. CONCLUSIONS: In settings affected by natural disaster or conflict,
      a high volume and wide repertoire of orthopaedic surgical procedures can be
      performed with good outcomes when minimum standards are in place. More demanding
      procedures like internal fixation may not always be feasible.

PMID- 25971656
TI  - Cosmological evolution of supermassive black holes in galactic centers unveiled
      by hard X-ray observations.
AB  - We review the current understanding of the cosmological evolution of supermassive
      black holes in galactic centers elucidated by X-ray surveys of active galactic
      nuclei (AGNs). Hard X-ray observations at energies above 2 keV are the most
      efficient and complete tools to find "obscured" AGNs, which are dominant
      populations among all AGNs. Combinations of surveys with various flux limits and
      survey area have enabled us to determine the space number density and obscuration
      properties of AGNs as a function of luminosity and redshift. The results have
      essentially solved the origin of the X-ray background in the energy band below
      ~10 keV. The downsizing (or anti-hierarchical) evolution that more luminous AGNs
      have the space-density peak at higher redshifts has been discovered, challenging
      theories of galaxy and black hole formation. Finally, we summarize unresolved
      issues on AGN evolution and prospects for future X-ray missions. 

PMID- 25971649
TI  - Management of endocrine disease: Secondary osteoporosis: pathophysiology and
      management.
AB  - Osteoporosis is a skeletal disorder characterized by decreased mass and
      compromised bone strength predisposing to an increased risk of fractures.
      Although idiopathic osteoporosis is the most common form of osteoporosis,
      secondary factors may contribute to the bone loss and increased fracture risk in
      patients presenting with fragility fractures or osteoporosis. Several medical
      conditions and medications significantly increase the risk for bone loss and
      skeletal fragility. This review focuses on some of the common causes of
      osteoporosis, addressing the underlying mechanisms, diagnostic approach and
      treatment of low bone mass in the presence of these conditions. 

PMID- 25971655
TI  - Neither pre-operative education or a minimally invasive procedure have any
      influence on the recovery time after total hip replacement.
AB  - PURPOSE: The purpose of this study was to evaluate pre-operative education versus
      no education and mini-invasive surgery versus standard surgery to reach complete
      independence. METHODS: We conducted a four-arm randomized controlled trial of 209
      patients. The primary outcome criterion was the time to reach complete functional
      independence. Secondary outcomes included the operative time, the estimated total
      blood loss, the pain level, the dose of morphine, and the time to discharge.
      RESULTS: There was no significant effect of either education (HR: 1.1; P = 0.77)
      or mini-invasive surgery (HR: 1.0; 95 %; P = 0.96) on the time to reach complete
      independence. The mini-invasive surgery group significantly reduced the total
      estimated blood loss (P = 0.0035) and decreased the dose of morphine necessary
      for titration in the recovery (P = 0.035). CONCLUSIONS: Neither pre-operative
      education nor mini-invasive surgery reduces the time to reach complete functional
      independence. Mini-invasive surgery significantly reduces blood loss and the need
      for morphine consumption.

PMID- 25971657
TI  - The EML4-ALK oncogene: targeting an essential growth driver in human cancer.
AB  - Targeting of essential growth drivers represents an ideal approach to cancer
      treatment. To identify such molecules in clinical specimens, we developed a
      highly sensitive functional screening system based on the preparation of
      retroviral cDNA expression libraries. By screening such a library of lung
      adenocarcinoma with a focus formation assay, we discovered the EML4-ALK fusion
      type oncogene. A small chromosomal inversion thus leads to fusion of the amino
      terminal portion of the microtubule-associated protein EML4 to the intracellular
      kinase domain of ALK, a receptor-type protein tyrosine kinase. Constitutive
      dimerization of EML4-ALK mediated by a dimerization motif of EML4 results in
      kinase activation. Specific inhibitors of the kinase activity of ALK have been
      developed as therapeutic drugs for EML4-ALK-positive lung cancer, three of which
      (crizotinib, ceritinib, and alectinib) have already been approved for clinical
      use. An overall clinical response rate of 93.5% for alectinib has shown that
      agents that target essential growth drivers can become magic bullets for cancer
      treatment. 

PMID- 25971658
TI  - Egg consumption and risk of type 2 diabetes among African Americans: The Jackson
      Heart Study.
AB  - BACKGROUND & AIMS: Type 2 diabetes (DM) disproportionally affects African
      Americans. Data on the association between egg consumption and risk of DM are
      sparse. We sought to examine whether egg consumption is associated with the
      prevalence and incidence of DM among African Americans. METHODS: We analyzed
      baseline data from 4568 participants of the Jackson Heart Study. Egg consumption
      was obtained using a food frequency questionnaire designed for this population.
      We used generalized estimating equations to calculate adjusted prevalence ratios
      of DM and Cox regression to estimate hazard ratios of DM with corresponding 95%
      confidence intervals (CI). RESULTS: The average age was 55 +/- 13 years and 64%
      of subjects were women. The median frequency of egg consumption was 2/week for
      men and 1/week for women. The prevalence of DM was 22% overall (21% of men and
      23% of women). Multivariable adjusted prevalence ratio [PR (95% CI)] for DM were:
      1.00 (ref), 1.14 (0.90-1.44), 1.33 (1.04-1.70), 1.33 (1.06-1.68), 1.26 (0.99
      1.61), and 1.52 (1.17-1.97) for egg consumption of <1/month, 1-3/month, 1/week,
      2/week, 3-4/week, and 5+/week, respectively, p for linear trend 0.0024.
      Corresponding multivariable adjusted hazard ratios were 1.00 (ref), 0.88 (0.65
      1.19), 0.94 (0.68-1.30), 0.91 (0.66-1.25), 1.11 (0.81-1.52), and 1.17 (0.81
      1.70), respectively, during a mean follow up of 7.3 years (p for linear trend
      0.22). CONCLUSIONS: While egg consumption was positively associated with
      prevalent DM, prospective analysis did not show an association of egg intake with
      incidence of DM among African Americans.

PMID- 25971660
TI  - Cancer and thrombosis: a fresh look at an old story.

PMID- 25971659
TI  - Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression
      in Lung Cancer.
AB  - PURPOSE: Alanine-serine-cysteine transporter 2 (ASCT2) expression has been
      demonstrated as a promising lung cancer biomarker. (2S,4R)-4
      [(18)F]Fluoroglutamine (4-[(18)F]fluoro-Gln) positron emission tomography (PET)
      was evaluated in preclinical models of non-small cell lung cancer as a
      quantitative, non-invasive measure of ASCT2 expression. PROCEDURES: In vivo
      microPET studies of 4-[(18)F]fluoro-Gln uptake were undertaken in human cell line
      xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically
      engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung
      cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors
      was evaluated by IHC and immunoblotting. RESULT: 4-[(18)F]Fluoro-Gln uptake, but
      not 2-deoxy-2-[(18)F]fluoro-D-glucose, correlated with relative ASCT2 levels in
      xenograft tumors. In genetically engineered mice, 4-[(18)F]fluoro-Gln
      accumulation was significantly elevated in lung tumors, relative to normal lung
      and cardiac tissues. CONCLUSIONS: 4-[(18)F]Fluoro-Gln PET appears to provide a
      non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung
      cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as
      precision imaging diagnostics in this setting.

PMID- 25971661
TI  - Comparison of dosing algorithms for acenocoumarol and phenprocoumon using
      clinical factors with the standard care in the Netherlands.
AB  - BACKGROUND: It has not been investigated how much the use of clinical factors in
      a dosing algorithm improves the percentage of time in therapeutic range (TTR).
      The present study aimed to compare the effect of dosing algorithms for
      acenocoumarol and phenprocoumon including clinical patient characteristics with
      standard care in the Netherlands. SETTING: The pre-EU-PACT study, an
      observational study in the Netherlands, was used to obtain standard care data.
      Data from the Dutch patients in the EU-PACT trial (comparing the use of a
      clinical algorithm with and without genetic information) was used for the
      clinical dosing algorithm. METHODS: For both acenocoumarol and phenprocoumon, the
      percentage of time in, below and above therapeutic International Normalized Ratio
      (INR) range during 12weeks after treatment initiation were assessed in both
      studies. RESULTS: During the weeks 2-12, the clinical dosing algorithm of
      acenocoumarol (80 patients) led to a higher TTR (74.3% versus 68.0% in range 2.0
      3.5, 95% Confidence interval [CI] difference: 0.5% to 11.8%), and a reduced
      percentage of time below INR 2 and above INR 3.5, compared with standard care
      (272 patients). For phenprocoumon, compared with standard care (484 patients), 80
      patients treated by the dosing algorithm did not obtained a significantly higher
      TTR in range 2.0-3.5 or a lower percentage of time above 3.5, however, they spent
      more time with INR below 2. CONCLUSION: The use of a clinical dosing algorithm
      for acenocoumarol seemed to improve the quality of anticoagulation therapy during
      the treatment of initial 2-12 weeks. For phenprocoumon, there was no
      statistically difference in anticoagulation control.

PMID- 25971662
TI  - Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair,
      and Cell Viability in Saccharomyces cerevisiae.
AB  - A critical feature of the intermolecular contacts that bind DNA to the histone
      octamer is the series of histone arginine residues that insert into the DNA minor
      groove at each superhelical location where the minor groove faces the histone
      octamer. One of these "sprocket" arginine residues, histone H4 R45, significantly
      affects chromatin structure in vivo and is lethal when mutated to alanine or
      cysteine in Saccharomyces cerevisiae (budding yeast). However, the roles of the
      remaining sprocket arginine residues (H3 R63, H3 R83, H2A R43, H2B R36, H2A R78,
      H3 R49) in chromatin structure and other cellular processes have not been well
      characterized. We have genetically characterized mutations in each of these
      histone residues when introduced either singly or in combination to yeast cells.
      We find that pairs of arginine residues that bind DNA adjacent to the DNA
      exit/entry sites in the nucleosome are lethal in yeast when mutated in
      combination and cause a defect in histone occupancy. Furthermore, mutations in
      individual residues compromise repair of UV-induced DNA lesions and affect gene
      expression and cryptic transcription. This study reveals simple rules for how the
      location and structural mode of DNA binding influence the biological function of
      each histone sprocket arginine residue.

PMID- 25971664
TI  - The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich
      Multichromosome Genome of Burkholderia cenocepacia.
AB  - Spontaneous mutations are ultimately essential for evolutionary change and are
      also the root cause of many diseases. However, until recently, both biological
      and technical barriers have prevented detailed analyses of mutation profiles,
      constraining our understanding of the mutation process to a few model organisms
      and leaving major gaps in our understanding of the role of genome content and
      structure on mutation. Here, we present a genome-wide view of the molecular
      mutation spectrum in Burkholderia cenocepacia, a clinically relevant pathogen
      with high %GC content and multiple chromosomes. We find that B. cenocepacia has
      low genome-wide mutation rates with insertion-deletion mutations biased toward
      deletions, consistent with the idea that deletion pressure reduces prokaryotic
      genome sizes. Unlike prior studies of other organisms, mutations in B.
      cenocepacia are not AT biased, which suggests that at least some genomes with
      high %GC content experience unusual base-substitution mutation pressure.
      Importantly, we also observe variation in both the rates and spectra of mutations
      among chromosomes and elevated G:C > T:A transversions in late-replicating
      regions. Thus, although some patterns of mutation appear to be highly conserved
      across cellular life, others vary between species and even between chromosomes of
      the same species, potentially influencing the evolution of nucleotide composition
      and genome architecture. 

PMID- 25971663
TI  - The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes
      Genomic Instability in Diploid Cells of Saccharomyces cerevisiae.
AB  - Genomic instability is a common feature found in cancer cells . Accordingly, many
      tumor suppressor genes identified in familiar cancer syndromes are involved in
      the maintenance of the stability of the genome during every cell division and are
      commonly referred to as caretakers. Inactivating mutations and epigenetic
      silencing of caretakers are thought to be the most important mechanisms that
      explain cancer-related genome instability. However, little is known of whether
      transient inactivation of caretaker proteins could trigger genome instability
      and, if so, what types of instability would occur. In this work, we show that a
      brief and reversible inactivation, during just one cell cycle, of the key
      phosphatase Cdc14 in the model organism Saccharomyces cerevisiae is enough to
      result in diploid cells with multiple gross chromosomal rearrangements and
      changes in ploidy. Interestingly, we observed that such transient loss yields a
      characteristic fingerprint whereby trisomies are often found in small-sized
      chromosomes, and gross chromosome rearrangements, often associated with
      concomitant loss of heterozygosity, are detected mainly on the ribosomal DNA
      bearing chromosome XII. Taking into account the key role of Cdc14 in preventing
      anaphase bridges, resetting replication origins, and controlling spindle dynamics
      in a well-defined window within anaphase, we speculate that the transient loss of
      Cdc14 activity causes cells to go through a single mitotic catastrophe with
      irreversible consequences for the genome stability of the progeny.

PMID- 25971665
TI  - Comprehensive Genetic Analysis of Paralogous Terminal Septin Subunits Shs1 and
      Cdc11 in Saccharomyces cerevisiae.
AB  - Septins are a family of GTP-binding proteins considered to be cytoskeletal
      elements because they self-assemble into filaments and other higher-order
      structures in vivo. In budding yeast, septins establish a diffusion barrier at
      the bud neck between a mother and daughter cell, promote membrane curvature
      there, and serve as a scaffold to recruit other proteins to the site of
      cytokinesis. However, the mechanism by which any septin engages a partner protein
      has been unclear. The two most related and recently evolved subunits appear to be
      Cdc11 and Shs1, and the basic building blocks for assembling septin structures
      are hetero-octameric rods (Cdc11-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11 and Shs1
      Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Shs1). Loss of Cdc11 is not normally tolerated,
      whereas cells lacking Shs1 do not appear grossly abnormal. We established several
      different sensitized genetic backgrounds wherein Shs1 is indispensable, which
      allowed us to carry out the first comprehensive and detailed genetic analysis of
      Shs1 in vivo. Our analysis revealed several novel insights, including: (i) the
      sole portion of Shs1 essential for its function is a predicted coiled-coil
      forming segment in its C-terminal extension (CTE); (ii) the CTE of Cdc11 shares
      this function; (iii) this role for the CTEs of Cdc11 and Shs1 is quite distinct
      from that of the CTEs of Cdc3 and Cdc12; and (iv) heterotypic Cdc11 and Shs1
      junctions likely occur in vivo.

PMID- 25971666
TI  - The Carboxy-Terminal Tails of Septins Cdc11 and Shs1 Recruit Myosin-II Binding
      Factor Bni5 to the Bud Neck in Saccharomyces cerevisiae.
AB  - Septins are a conserved family of GTP-binding proteins that form heterooctameric
      complexes that assemble into higher-order structures. In yeast, septin
      superstructure at the bud neck serves as a barrier to separate a daughter cell
      from its mother and as a scaffold to recruit the proteins that execute
      cytokinesis. However, how septins recruit specific factors has not been well
      characterized. In the accompanying article in this issue, (Finnigan et al. 2015),
      we demonstrated that the C-terminal extensions (CTEs) of the alternative terminal
      subunits of septin heterooctamers, Cdc11 and Shs1, share a role required for
      optimal septin function in vivo. Here we describe our use of unbiased genetic
      approaches (both selection of dosage suppressors and analysis of synthetic
      interactions) that pinpointed Bni5 as a protein that interacts with the CTEs of
      Cdc11 and Shs1. Furthermore, we used three independent methods-construction of
      chimeric proteins, noncovalent tethering mediated by a GFP-targeted nanobody, and
      imaging by fluorescence microscopy-to confirm that a physiologically important
      function of the CTEs of Cdc11 and Shs1 is optimizing recruitment of Bni5 and
      thereby ensuring efficient localization at the bud neck of Myo1, the type II
      myosin of the actomyosin contractile ring.Related article in GENETICS: Finnigan,
      G. C. et al., 2015 Comprehensive Genetic Analysis of Paralogous Terminal Septin
      Subunits Shs1 and Cdc11 in Saccharomyces cerevisiae. Genetics 200: 841-861.

PMID- 25971667
TI  - Germ Cell Segregation from the Drosophila Soma Is Controlled by an Inhibitory
      Threshold Set by the Arf-GEF Steppke.
AB  - Germline cells segregate from the soma to maintain their totipotency, but the
      cellular mechanisms of this segregation are unclear. The Drosophila melanogaster
      embryo forms a posterior group of primordial germline cells (PGCs) by their
      division from the syncytial soma. Extended plasma membrane furrows enclose the
      PGCs in response to the germ plasm protein Germ cell-less (Gcl) and Rho1
      actomyosin activity. Recently, we found that loss of the Arf-GEF Steppke (Step)
      leads to similar Rho1-dependent plasma membrane extensions but from
      pseudocleavage furrows of the soma. Here, we report that the loss of step also
      leads to premature formation of a large cell group at the anterior pole of the
      embryo . These anterior cells lacked germ plasm, but budded and formed at the
      same time as posterior PGCs, and then divided asynchronously as PGCs also do.
      With genetic analyses we found that Step normally activates Arf small G proteins
      and antagonizes Rho1-actomyosin pathways to inhibit anterior cell formation. A
      uniform distribution of step mRNA around the one-cell embryo cortex suggested
      that Step restricts cell formation through a global control mechanism. Thus, we
      examined the effect of Step on PGC formation at the posterior pole. Reducing Gcl
      or Rho1 levels decreased PGC numbers, but additional step RNAi restored their
      numbers. Reciprocally, GFP-Step overexpression induced dosage- and Arf-GEF
      dependent loss of PGCs, an effect worsened by reducing Gcl or actomyosin pathway
      activity. We propose that a global distribution of Step normally sets an
      inhibitory threshold for Rho1 activity to restrict early cell formation to the
      posterior.

PMID- 25971668
TI  - Chromosome-Specific Painting in Cucumis Species Using Bulked Oligonucleotides.
AB  - Chromosome-specific painting is a powerful technique in molecular cytogenetic and
      genome research. We developed an oligonucleotide (oligo)-based chromosome
      painting technique in cucumber (Cucumis sativus) that will be applicable in any
      plant species with a sequenced genome. Oligos specific to a single chromosome of
      cucumber were identified using a newly developed bioinformatic pipeline and then
      massively synthesized de novo in parallel. The synthesized oligos were amplified
      and labeled with biotin or digoxigenin for use in fluorescence in situ
      hybridization (FISH). We developed three different probes with each containing
      23,000-27,000 oligos. These probes spanned 8.3-17 Mb of DNA on targeted cucumber
      chromosomes and had the densities of 1.5-3.2 oligos per kilobases. These probes
      produced FISH signals on a single cucumber chromosome and were used to paint
      homeologous chromosomes in other Cucumis species diverged from cucumber for up to
      12 million years. The bulked oligo probes allowed us to track a single chromosome
      in early stages during meiosis. We were able to precisely map the pairing between
      cucumber chromosome 7 and chromosome 1 of Cucumis hystrix in a F1 hybrid. These
      two homeologous chromosomes paired in 71% of prophase I cells but only 25% of
      metaphase I cells, which may provide an explanation of the higher recombination
      rates compared to the chiasma frequencies between homeologous chromosomes
      reported in plant hybrids.

PMID- 25971671
TI  - 2014 ASMS Fall Workshop: Ion Mobility Mass Spectrometry.

PMID- 25971669
TI  - Programa Geracao Biz, Mozambique: how did this adolescent health initiative grow
      from a pilot to a national programme, and what did it achieve?
AB  - Adolescent sexual and reproductive health gained particular traction in
      Mozambique following the 1994 International Conference on Population and
      Development leading to the inception of Programa Geracao Biz (PGB), a multi
      sectoral initiative that was piloted starting in 1999 and fully scaled-up to all
      provinces by 2007. We conducted a systematic review of the literature to gather
      information on PGB and analyzed how it planned and managed the scale-up effort
      using the WHO-ExpandNet framework. PGB's activities comprised a clear and
      credible innovation. Appropriate resource and user organizations further
      facilitated national scale-up. Challenges relating to the complex nature of the
      multi-sectoral approach and resistance due to norms about adolescent sexual and
      reproductive health hindered scaling-up in some geographic areas. The national
      government exhibited commitment and ownership to PGB through budgetary support
      and integration into multiple policies. This study adds to the documentation of
      successful scaling-up strategies that can provide guidance for policy makers and
      programme managers. 

PMID- 25971670
TI  - Tracking the Magnetron Motion in FT-ICR Mass Spectrometry.
AB  - In Fourier transform ion cyclotron resonance spectrometry (FT-ICR MS) the ion
      magnetron motion is not usually directly measured, yet its contribution to the
      performance of the FT-ICR cell is important. Its presence is manifested primarily
      by the appearance of even-numbered harmonics in the spectra. In this work, the
      relationship between the ion magnetron motion in the ICR cell and the intensities
      of the second harmonic signal and its sideband peak in the FT-ICR spectrum is
      studied. Ion motion simulations show that during a cyclotron motion excitation of
      ions which are offset to the cell axis, a position-dependent radial drift of the
      cyclotron center takes place. This radial drift can be directed outwards if the
      ion is initially offset towards one of the detection electrodes, or it can be
      directed inwards if the ion is initially offset towards one of the excitation
      electrodes. Consequently, a magnetron orbit diameter can increase or decrease
      during a resonant cyclotron excitation. A method has been developed to study this
      behavior of the magnetron motion by acquiring a series of FT-ICR spectra using
      varied post-capture delay (PCD) time intervals. PCD is the delay time after the
      capture of the ions in the cell before the cyclotron excitation of the ion is
      started. Plotting the relative intensity of the second harmonic sideband peak
      versus the PCD in each mass spectrum leads to an oscillating "PCD curve". The
      position and height of minima and maxima of this curve can be used to interpret
      the size and the position of the magnetron orbit. Ion motion simulations show
      that an off-axis magnetron orbit generates even-numbered harmonic peaks with
      sidebands at a distance of one magnetron frequency and multiples of it. This
      magnetron offset is due to a radial offset of the electric field axis versus the
      geometric cell axis. In this work, we also show how this offset of the radial
      electric field center can be corrected by applying appropriate DC correction
      voltages to the mantle electrodes of the ICR cell while observing the signals of
      the second harmonic peak group. The field correction leads to a definite
      performance increase in terms of resolving power and mass accuracy, and the mass
      spectrum contains intensity-minimized even-numbered harmonics. This is very
      important in the case of high performance cells, particularly the dynamically
      harmonized cell, since the magnetron motion can severely impair the averaging
      effect for dynamic harmonization and can therefore reduce the resolving power.

PMID- 25971673
TI  - Traditional plant use in Burkina Faso (West Africa): a national-scale analysis
      with focus on traditional medicine.
AB  - BACKGROUND: The West African country of Burkina Faso (BFA) is an example for the
      enduring importance of traditional plant use today. A large proportion of its 17
      million inhabitants lives in rural communities and strongly depends on local
      plant products for their livelihood. However, literature on traditional plant use
      is still scarce and a comprehensive analysis for the country is still missing.
      METHODS: In this study we combine the information of a recently published plant
      checklist with information from ethnobotanical literature for a comprehensive,
      national scale analysis of plant use in Burkina Faso. We quantify the application
      of plant species in 10 different use categories, evaluate plant use on a plant
      family level and use the relative importance index to rank all species in the
      country according to their usefulness. We focus on traditional medicine and
      quantify the use of plants as remedy against 22 classes of health disorders,
      evaluate plant use in traditional medicine on the level of plant families and
      rank all species used in traditional medicine according to their respective
      usefulness. RESULTS: A total of 1033 species (50%) in Burkina Faso had a
      documented use. Traditional medicine, human nutrition and animal fodder were the
      most important use categories. The 12 most common plant families in BFA differed
      considerably in their usefulness and application. Fabaceae, Poaceae and Malvaceae
      were the plant families with the most used species. In this study Khaya
      senegalensis, Adansonia digitata and Diospyros mespiliformis were ranked the top
      useful plants in BFA. Infections/Infestations, digestive system disorders and
      genitourinary disorders are the health problems most commonly addressed with
      medicinal plants. Fabaceae, Poaceae, Asteraceae, Apocynaceae, Malvaceae and
      Rubiaceae were the most important plant families in traditional medicine.
      Tamarindus indica, Vitellaria paradoxa and Adansonia digitata were ranked the
      most important medicinal plants. CONCLUSIONS: The national-scale analysis
      revealed systematic patterns of traditional plant use throughout BFA. These
      results are of interest for applied research, as a detailed knowledge of
      traditional plant use can a) help to communicate conservation needs and b)
      facilitate future research on drug screening.

PMID- 25971675
TI  - Colorectal cancer: A circuitous way to target p53.

PMID- 25971674
TI  - Peculiarities of autoimmune thyroid diseases in children with Turner or Down
      syndrome: an overview.
AB  - Aim of this commentary is to summarize the salient literature news on the
      relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome
      (DS) or Turner syndrome (TS).According to literature reports both Hashimoto's
      thyroiditis (HT) and Graves' disease (GD) are more frequent in children with DS
      or TS than in those without these chromosomopathies.An up-regulation of
      proinflammatory cytokines might be responsible for the enhanced susceptibility of
      TS children to ATDs, whereas a dysregulation of immune system may favor the
      development of ATDs in DS.In TS children biochemical presentation of HT is less
      severe than in peer controls. In both DS and TS GD picture at the time of
      diagnosis is not significantly different than in the pediatric general
      population.The evolution over time of GD in DS and TS does not differ from that
      observed in the pediatric general population, whereas the evolution of HT in both
      TS and DS is more severe than in girls without these chromosomopathies.
      CONCLUSIONS: The association with TS or DS is able to affect both epidemiology
      and course of ATDs by conditioning: a) an increased susceptibility to these
      disorders; b) a less severe biochemical presentation and a more severe evolutive
      pattern of HT in TS girls; c) a more severe biochemical presentation and
      evolution of HT in DS patients.

PMID- 25971677
TI  - Occupational exposure to extremely low-frequency magnetic fields and electrical
      shocks and acute myeloid leukemia in four Nordic countries.
AB  - OBJECTIVE: We studied the association between occupational exposure to extremely
      low-frequency magnetic fields (ELF-MF) and electrical shocks and acute myeloid
      leukemia (AML) in the Nordic Occupational Cancer cohort (NOCCA). METHODS: We
      included 5,409 adult AML cases diagnosed between 1961 and 2005 in Finland,
      Iceland, Norway, and Sweden and 27,045 controls matched by age, sex, and country.
      Lifetime occupational ELF-MF exposure and risk of electrical shocks were assigned
      to jobs reported in the censuses using job-exposure matrices. We estimated hazard
      ratios (HRs) and 95 % confidence intervals (95 % CIs) using conditional logistic
      regression adjusted for concurrent occupational exposures relevant for AML risk
      (e.g., benzene, ionizing radiation). We conducted sensitivity analyses with
      different assumptions to assess the robustness of our results. RESULTS:
      Approximately 40 % of the subjects were ever occupationally exposed to low levels
      and 7 % to high levels of ELF-MF, whereas 18 % were ever at low risk and 15 % at
      high risk of electrical shocks. We did not observe an association between
      occupational exposure to neither ELF-MF nor electrical shocks and AML. The HR was
      0.88 (95 % CI 0.77-1.01) for subjects with high levels of ELF-MF exposure and
      0.94 (95 % CI 0.85-1.05) for subjects with high risk of electrical shocks as
      compared to those with background-level exposure. Results remained materially
      unchanged in sensitivity analyses with different assumptions. CONCLUSION: Our
      results do not support an association between occupational ELF-MF or electric
      shock exposure and AML.

PMID- 25971678
TI  - Three decomposition products of valepotriates from Valeriana jatamansi and their
      cytotoxic activity.
AB  - Three new decomposition products of valepotriates, valtrals A-C (1-3), and two
      known products, baldrinal and homobaldrinal, are formed during the isolation
      procedure of the ethanol extract of the whole plants of Valeriana jatamansi.
      Their structures were determined by spectroscopic methods including IR, MS, 1D,
      and 2D NMR experiments. Compounds 1-3 showed selective cytotoxicity against
      metastatic prostate cancer (PC-3M) and colon cancer (HCT-8) cell lines. 

PMID- 25971679
TI  - Catastrophic health expenditure and its determinants in Kenya slum communities.
AB  - BACKGROUND: In Kenya, where 60 to 80% of the urban residents live in informal
      settlements (frequently referred to as slums), out-of-pocket (OOP) payments
      account for more than a third of national health expenditures. However, little is
      known on the extent to which these OOP payments are associated with personal or
      household financial catastrophe in the slums. This paper seeks to examine the
      incidence and determinants of catastrophic health expenditure among urban slum
      communities in Kenya. METHODS: We use a unique dataset on informal settlement
      residents in Kenya and various approaches that relate households OOP payments for
      healthcare to total expenditures adjusted for subsistence, or income. We
      classified households whose OOP was in excess of a predefined threshold as facing
      catastrophic health expenditures (CHE), and identified the determinants of CHE
      using multivariate logistic regression analysis. RESULTS: The results indicate
      that the proportion of households facing CHE varies widely between 1.52% and
      28.38% depending on the method and the threshold used. A core set of variables
      were found to be key determinants of CHE. The number of working adults in a
      household and membership in a social safety net appear to reduce the risk of
      catastrophic expenditure. Conversely, seeking care in a public or private
      hospital increases the risk of CHE. CONCLUSION: This study suggests that a
      substantial proportion of residents of informal settlements in Kenya face CHE and
      would likely forgo health care they need but cannot afford. Mechanisms that pool
      risk and cost (insurance) are needed to protect slum residents from CHE and
      improve equity in health care access and payment.

PMID- 25971681
TI  - Musashi-1 Expression is a Prognostic Factor in Ovarian Adenocarcinoma and
      Correlates with ALDH-1 Expression.
AB  - The presence of cancer stem-like cells (CSCs) has been demonstrated to be
      associated with tumor metastasis, chemoresistance, and rapid recurrence of
      various tumors. The impact of CSC-related markers in the metastasis and prognosis
      of ovarian cancer has not been well established. In this study, the protein
      expression of musashi-1 and ALDH1 was measured using immunohistochemistry.
      Results demonstrated that the percentage of positive musashi-1 and ALDH1
      expression were significantly higher in ovarian serous adenocarcinomas, mucinous
      adenocarcinomas and clear cell adenocarcinomas than in cystadenomas and normal
      tissues. The percentage of positive musashi-1 and ALDH1 expression were
      significantly lower in patients identified with clinical stage I or II ovarian
      adenocarcinomas without lymph node metastasis compared to patients with clinical
      stage III or IV tumors and lymph node metastasis. The expression of musashi-1 and
      ALDH1 was found to be highly consistent in ovarian adenocarcinomas. Univariate
      Kaplan-Meier analysis showed a negative correlation between musashi-1 or ALDH1
      expression and overall survival. Multivariate Cox regression analysis showed that
      positive expression of musashi-1 or ALDH1 in ovarian adenocarcinoma was an
      independent predictor of poor prognosis. Our study suggested that musashi-1 and
      ALDH1 expression are closely related to metastasis of ovarian adenocarcinoma. The
      positive expression of musashi-1 and ALDH1 might be a poor-prognostic factor of
      ovarian adenocarcinoma. 

PMID- 25971680
TI  - Psychological impact of lifestyle-related disease disclosure at general checkup:
      a prospective cohort study.
AB  - BACKGROUND: Little is known about psychological impact of disclosing lifestyle
      related diseases. Previous studies discussed the long-term psychological impact
      of disease disclosure, and a significant psychological impact was not observed.
      This study clarified the psychological impact on anxiety state of patients when
      lifestyle-related diseases are disclosed at general checkups for local residents.
      In particular, this study evaluated the short-term impact on patients, and how
      the notification of abnormal values and the disclosure of disease at general
      checkups affect patients' subsequent behavioral changes. METHODS: The study
      design was a prospective cohort study. We compared the anxiety state of
      participants using a self-administered anxiety assessment scale, State-Trait
      Anxiety Inventory (STAI), before and after Physician's explanation of abnormal
      values in markers of lifestyle-related diseases. The participants were those
      between the age of 40 and 75 years who underwent general checkups at two primary
      care facilities. In addition, we assessed the effects on lifestyle habits and the
      psychological impact caused by general checkup using STAI and a survey on
      behavioral changes one month after the checkup. RESULTS: The valid response rate
      at the survey of the general checkup was 92% (534/578). Of those who showed
      abnormal levels in markers of lifestyle-related diseases, anxiety was augmented
      significantly among those who responded that the physician had told them of their
      diagnosis compared to those who responded that the physician had not told them of
      their diagnosis (Wilcoxon rank-sum test, P < 0.007). The percentage of patients
      whose state anxiety scale of STAI increased >=5 points was 30% in the disease
      disclosed group (33/111) and 17% in the disease undisclosed group (27/159),
      respectively. The risk ratio was 1.5 (95% CI: 1.1-2.0). One month after the
      general checkup, overall anxiety diminished regardless of whether diagnosis of
      lifestyle-related diseases was disclosed to patients notified of abnormal values.
      In addition, improvements in daily life behaviors as a result of notification of
      abnormalities or disclosure of diagnosis at general checkup were not observed.
      CONCLUSION: Even in a general checkup for the general population, disclosing non
      critical diseases such as lifestyle-related diseases exacerbated anxiety as a
      short-term psychological impact.

PMID- 25971682
TI  - PQ401, an IGF-1R inhibitor, induces apoptosis and inhibits growth, proliferation
      and migration of glioma cells.
AB  - Growth factor signalling pathways transduce extra-cellular physiological cues to
      guide cells to maintain critical cellular functions, including cell
      proliferation, survival and metabolism. Dysregulation of certain growth factor
      signalling pathways has been shown as a major route to promote tumourigenesis.
      Glioma is a type of aggressive malignant tumour with no effective systematic
      therapy so far. Overexpression or hyperactivation of IGF-1R has been observed to
      be tightly associated with glioma progression and poor prognosis. Here, we
      examined the biological effects of a specific IGF-1R inhibitor, PQ401, on
      suppressing U87MG glioma cell growth and migration. Specifically, we observed
      that PQ401 not only induced cellular apoptosis in U87MG cells and subsequently
      reduced cell viability and proliferation but also attenuated cell mobility in
      vitro. More importantly, through a mouse xenograft model, we observed that
      administration of PQ401 on mice led to suppression of glioma tumour growth in
      vivo. In summary, our study suggests that PQ401 may serve as a promising leading
      drug for treating glioma patients with elevated IGF-1R signalling. 

PMID- 25971683
TI  - Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism
      among Egyptian healthcare workers with and without a hepatitis C virus-specific
      cellular immune response.
AB  - The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated
      with spontaneous hepatitis C virus (HCV) clearance and treatment response. The
      distribution and correlation of an IL28B.rs12979860 single-nucleotide
      polymorphism (SNP) with HCV-specific cell-mediated immune (CMI) responses among
      Egyptian healthcare workers (HCWs) is not known. We determined this relationship
      in 402 HCWs who serve a patient cohort with ~85% HCV prevalence. We enrolled 402
      HCWs in four groups: group 1 (n = 258), seronegative aviremic subjects; group 2
      (n = 25), seronegative viremic subjects; group 3 (n = 41), subjects with
      spontaneously resolved HCV infection; and group 4 (n = 78), chronic HCV patients.
      All subjects were tested for an HCV-specific CMI response using an ex-vivo
      interferon-gamma (IFNgamma) ELISpot assay with nine HCV genotype-4a overlapping
      15-mer peptide pools corresponding to all of the HCV proteins. All subjects were
      tested for IL28B.rs12979860 SNP by real-time PCR. An HCV-specific CMI was
      demonstrated in ~27% of the seronegative aviremic HCWs (group 1), suggesting
      clearance of infection after low-level exposure to HCV. The frequency of
      IL28B.rs12979860 C allele homozygosity in the four groups was 49%, 48%, 49%, and
      23%, while that of the T allele was 14%, 16%, 12 and 19%, respectively,
      suggesting differential distributions among subjects with different HCV status.
      As reported, IL28B.rs12979860 predicted the outcome of HCV infection (p < 0.05),
      but we did not find any relationship between the IL28B genotypes and the outcome
      of HCV-specific CMI responses in the four groups (p > 0.05). The data show
      differential IL28B.rs12979860 genotype distribution among Egyptian HCWs with
      different HCV status and could not predict the outcome of HCV-specific CMI
      responses.

PMID- 25971685
TI  - [Commentary on the article "Skin cancer screening in Germany" by Blum et al].

PMID- 25971686
TI  - Supplemented vs. unsupplemented human milk on bone mineralization in very low
      birth weight preterm infants: a randomized clinical trial.
AB  - Very low birth weight preterm newborns weighing less than 1500 g were randomized
      to receive human milk supplemented with FM 85(r) or not. They have similar bone
      mineral content (BMC) at baseline, but, at the end of study, BMC was increasingly
      higher in the FM 85(r) group. INTRODUCTION: The purpose of this study is to
      evaluate the effectiveness of a human milk supplement (FM 85(r); Nestle, Vevey,
      Switzerland) developed for the purpose of improving nutrition, including bone
      mineralization, in very low birth weight preterm newborns. METHODS: Preterm
      infants weighing less than 1500 g at birth admitted to the neonatal intensive
      care unit of a university hospital were studied. During hospitalization, they
      were fed at least 50 % of human milk. Newborns with >=20 days of age were
      randomly assigned to the intervention group (n = 19) to receive human milk
      supplemented with FM 85(r) or to a control group (n = 19) to receive human milk
      only. Anthropometric measurements, whole-body bone densitometry (DXA), and
      biochemical tests were performed at study entry and at the end of the study
      (shortly before discharge when the infant had reached 2000 g). RESULTS: There
      were no start- or end-of-study differences between the two groups, except for
      daily increase in length (p = 0.010). At baseline, both groups had similar BMC:
      5.49 +/- 3.65 vs. 4.34 +/- 2.98 g (p = 0.39) for the intervention and control
      group, respectively. However, at the end of the study, BMC was higher in the
      intervention group: 10.3 +/- 4.71 vs. 6.19 +/- 3.23 g (p = 0.003). The mean
      increase in BMC during the observation period was 4.90 +/- 4.46 g for the
      intervention group and 1.86 +/- 3.17 g for the control group (p = 0.020). Serum
      alkaline phosphatase levels were higher in the control group (720 +/- 465 vs. 391
      +/- 177 IU/L; p = 0.007). CONCLUSIONS: Our data suggest that supplementation of
      human milk with FM 85(r) leads to improved bone mineralization in very low birth
      weight preterm newborns.

PMID- 25971688
TI  - An assessment of the supply, programmatic use, and regulatory issues of single
      low-dose primaquine as a Plasmodium falciparum gametocytocide for sub-Saharan
      Africa.
AB  - BACKGROUND: Global ambitions to eliminate malaria are intensifying, underscoring
      a critical need for transmission blocking tools. In 2012, the WHO recommended the
      use of 0.25 mg/kg of single low-dose (SLD) primaquine to stop Plasmodium
      falciparum transmission. To ensure the availability of SLD primaquine to
      countries in need of this tool, more information on the supply, programmatic, and
      regulatory barriers to the rollout of SLD primaquine is required. METHODS:
      Challenges to the rollout of SLD primaquine in sub-Saharan Africa were
      established through semi-structured qualitative interviews with three primaquine
      manufacturers, 43 key informants from Ethiopia, Senegal, Swaziland, Zambia, and
      Tanzania, and 16 malaria research experts. RESULTS: Sanofi and Remedica are the
      only two sources of SRA-approved primaquine suitable for procurement by
      international donors. Neither manufacturer produces primaquine tablet strengths
      suitable for the transmission blocking indication. In-country key informants
      revealed that the WHO weight-based recommendation to use SLD primaquine is
      challenging to implement in actual field settings. Malaria programmes expressed
      safety concerns of SLD primaquine use in individuals with glucose-6-phosphate
      dehydrogenase (G6PD) deficiency, as well as potential interactions between
      primaquine and co-morbidities, and drug-drug interactions with HIV and/or
      tuberculosis treatments. Regulatory processes are a major barrier to the rollout
      of SLD primaquine, requiring multiple steps at both the country and global level.
      Despite these barriers, demand for SLD primaquine is growing, and malaria
      researchers are interested in primaquine deployment through mass screen and treat
      and/or mass drug administration campaigns. CONCLUSION: Demand for primaquine as a
      transmission blocking agent is growing rapidly yet multiple barriers to SLD
      primaquine use exist. Research is needed to define the therapeutic dose range,
      which will guide dosing regimens in the field, inform the development of new,
      lower strength primaquine tablets and/or formulation(s), and allay programmatic
      safety concerns in individuals with G6PD deficiency. Potential interactions
      between primaquine and co-morbidities and treatments should be explored. To
      minimize regulatory delays, countries need to prepare for product registration at
      an early stage, WHO prequalification for suitable primaquine tablet strengths
      and/or new formulations should be sought, and in the meanwhile only Stringent
      Regulatory Authority (SRA)-approved primaquine should be used.

PMID- 25971689
TI  - Do we need a threshold conception of competence?
AB  - On the standard view we assess a person's competence by considering her relevant
      abilities without reference to the actual decision she is about to make. If she
      is deemed to satisfy certain threshold conditions of competence, it is still an
      open question whether her decision could ever be overruled on account of its
      harmful consequences for her ('hard paternalism'). In practice, however, one
      normally uses a variable, risk dependent conception of competence, which really
      means that in considering whether or not to respect a person's decision-making
      authority we weigh her decision on several relevant dimensions at the same time:
      its harmful consequences, its importance in terms of the person's own relevant
      values, the infringement of her autonomy involved in overruling it, and her
      decision-making abilities. I argue that we should openly recognize the multi
      dimensional nature of this judgment. This implies rejecting both the threshold
      conception of competence and the categorical distinction between hard and soft
      paternalism. 

PMID- 25971690
TI  - Endocrinology and art. Hypertrichosis and dwarfism in a painting of Agostino
      Carracci (1598-1600).

PMID- 25971691
TI  - Muscle stem cells contribute to myofibres in sedentary adult mice.
AB  - Skeletal muscle is essential for mobility, stability and whole body metabolism,
      and muscle loss, for instance, during sarcopenia, has profound consequences.
      Satellite cells (muscle stem cells) have been hypothesized, but not yet
      demonstrated, to contribute to muscle homeostasis and a decline in their
      contribution to myofibre homeostasis to play a part in sarcopenia. To test their
      role in muscle maintenance, we genetically labelled and ablated satellite cells
      in adult sedentary mice. We demonstrate via genetic lineage experiments that,
      even in the absence of injury, satellite cells contribute to myofibres in all
      adult muscles, although the extent and timing differs. However, genetic ablation
      experiments showed that satellite cells are not globally required to maintain
      myofibre cross-sectional area of uninjured adult muscle. 

PMID- 25971692
TI  - [Handover between home and respite care facilities : Delphi survey within the
      context of continuity of care for people with dementia].
AB  - BACKGROUND: Criteria for the handover between healthcare settings were identified
      based on a review and on results of empirical data. AIM: This study was carried
      out to select the most relevant criteria for defining the quality of continuity
      of care of people with dementia (PwD) in the context of the handover between care
      at home and respite care facilities. MATERIAL AND METHODS: A modified classical
      two-step Delphi design was used in combination with a group Delphi design.
      RESULTS: A total of 28 core criteria with a consensus strength of > 60 % are
      presented. Safety-relevant information, especially the personal habits of PwD and
      the role of informal caregivers in the handover between care settings are
      important. Furthermore, the following general principles to ensure the quality of
      continuity of the care of PwD were deduced: completeness, verification, multipath
      communication, timeliness and topicality, accessibility and defined
      responsibilities, roles and standardization. DISCUSSION: A successful transition
      of PwD to respite care facilities relies on the provision of relevant
      information, considering personal habits, before the day of transition.
      Furthermore, a timely preparation for discharge is important. The individual
      needs of the informal caregivers with regard to their support should be
      considered. Professionals who are responsible in handover processes should have
      solid communication competence in order to collect relevant information from
      informal caregivers, who have a strong individual care experience with the PwD.

PMID- 25971694
TI  - Hepatitis C virus infection in the general population: A large community-based
      study in Mianyang, West China.
AB  - Hepatitis C virus (HCV) infection remains a major public health problem. The
      objective of the current study was to reveal the seroepidemiology of HCV in the
      general population in Mianyang City. This study collected 438,575 blood samples
      from participants who had enrolled in the National Science and Technology
      Development Project and their demographic information, and then evaluated HCV
      antibody and alanine aminotransferase (ALT) levels. The overall anti-HCV positive
      rate was 0.80% (3,491/438,575) in the Mianyang general population, and it was
      1.19% in rural population and 0.20% in urban. Anti-HCV positive rate increased
      with age, peaked at 45-54 years (2.01%), and then decreased. Anti-HCV prevalence
      was higher in males (0.89%) than that in females (0.73%). The prevalence of anti
      HCV in participants with a history of blood transfusion, surgery, or with a
      previous diagnosis of hypertension was higher. The abnormal ALT levels (> 40
      IU/L) were observed in 50.11% and 7.74% of anti-HCV positive and negative groups,
      respectively. In anti-HCV positive groups, the rate of abnormal ALT levels was
      higher in 55-64 age groups, male, and rural population. Though Mianyang was a low
      endemic area for HCV infection, the alarming fact was the large number of
      abnormal ALT levels in patients related to hepatitis C. This revealed delayed
      diagnosis and treatment of HCV infections. It is a necessity to promote early
      diagnosis and timely treatment of HCV infections. 

PMID- 25971695
TI  - A comparative study of contrast enhanced ultrasound and contrast enhanced
      magnetic resonance imaging for the detection and characterization of hepatic
      hemangiomas.
AB  - This study aims to compare contrast enhanced ultrasound (CEUS) and contrast
      enhanced magnetic resonance imaging (CEMRI) for the detection and
      characterization of hepatic hemangiomas. Included in this retrospective study
      were 83 histopathologically confirmed lesions of hemangioma in 66 hospitalized
      patients who underwent both CEUS and CEMRI and received surgery. The enhancement
      patterns on CEUS and CEMRI in each lesion were compared and analyzed. In
      addition, data obtained by the two modalities were then compared with the
      pathological findings to determine their value in differential diagnosis of
      hepatic hemangiomas. CEUS diagnosed 78 lesions of hemangioma against 80 by CEMRI.
      There were no statistical significant differences in the diagnostic value between
      CEUS and CEMRI in terms of sensitivity (88.0% vs. 92.8%), specificity (99.0% vs.
      99.4%), accuracy (97.3% vs. 98.4%), positive predictive value (93.6% vs. 96.3%),
      and negative predictive value (98.0% vs. 98.8%) (p > 0.05, all). In the arterial
      phase, the main enhancement pattern on both CEUS and CEMRI was peripheral nodular
      enhancement (73 vs. 76), but lesions with diffuse enhancement on CEUS outnumbered
      those on CEMRI (3 vs. 1) and lesions with circular enhancement on CEMRI
      outnumbered those on CEUS (3 vs. 2). In the portal venous phase and delayed
      phase, the main enhancement pattern was hyperechoic change on CEUS and
      hyperintense on CEMRI (66 vs. 65), some lesions presented isoechoic change (12
      vs. 15). These results suggested CEUS, an equivalent to CEMRI, may have an added
      diagnostic value in hemangiomas. 

PMID- 25971696
TI  - Hepatitis B virus promotes autophagic degradation but not replication in
      autophagosome.
AB  - In this study, we investigate the relationship of hepatitis B virus (HBV)
      infection and autophagy. HepG2 cells and HepG2 cells infected with HBV
      (HepG2.2.15) were transfected with GFP-LC3 (green fluorescence protein conjugated
      with microtubule-associated protein 1 light chain 3) expression vector and
      autophagy status was then examined with confocal microscope. HepG2.2.15 cells
      were further treated with serum-free medium or 3-methyladenine (3-MA), and
      subjected to Hepatitis B core antigen (HBcAg), Hepatitis B surface antigen
      (HBsAg), or hepatitis B polymerase protein detection by immunohistochemistry.
      Localization of the GFP-LC3 and the HBV proteins was observed by confocal
      fluorescence microscope. The level of SQSTM1/p62 protein was also evaluated by
      Western blot analysis. In contrast to a diffuse distribution in HepG2 cells, GFP
      LC3 formed distinct punctate dots, which were further enhanced by nutritional
      starvation, in HepG2.2.15 cells. The expression of hepatitis B polymerase and
      HBcAg, but not HBsAg, was positively correlated with the autophagic intensity.
      However, no co-localizations were observed between HBV proteins and
      autophagosomes. Suppression of autophagy reduced the expression of hepatitis B
      polymerase and HBcAg, but not HBsAg. Western blot showed that SQSTM1/p62 protein
      level was declined in HepG2.2.15 cells comparing HepG2 cells, and further reduced
      while upon serum starvation. In conclusion, HBV infection induces autophagic
      degradation and autophagy. Autophagy is critical for HBV replication. However HBV
      replication does not take place in autophagosomes. 

PMID- 25971699
TI  - The impact of intra-abdominal pressure on the stroke volume variation and
      plethysmographic variability index in patients undergoing laparoscopic
      cholecystectomy.
AB  - The purpose of the present study was to evaluate the effect of increasing intra
      abdominal pressure (IAP) on stroke volume variation (SVV) and plethysmographic
      variability index (PVI) in patients undergoing laparoscopic cholecystectomy. PVI
      examined by Masimo Radical 7 pulse oximeter and SVV determined using
      FloTrac/Vigileo were monitored simultaneously in forty-five patients undergoing
      laparoscopic cholecystectomy (LC). Mean arterial blood pressure (MAP), heart rate
      (HR), cardiac index (CI), perfusion index (PI), airway pressures (P), SVV, and
      PVI were also recorded at the following predetermined time: 5 min after
      endotracheal intubation (T1), 5 min after pneumoperitoneum at 5 mmHg (T2), 5 min
      after pneumoperitoneum at 10 mmHg (T3), 5 min after pneumoperitoneum at 15 mmHg
      (T4), and 5 min after the termination of pneumoperitoneum (T5). Forty-five
      patients with a total of 225 pairs of measurements were included in the analysis.
      Compared with the values at T1, both SVV and PVI showed significant progressive
      increases as the IAP was adjusted from 5 to 10, 15 mmHg at T2, T3, and T4,
      respectively. No significant difference was found when the pneumoperitoneum was
      terminated at T5. Further regressive analysis indicated strong relationships
      between SVV and IAP (r = 0.8118, p < 0.001), PVI and IAP(r = 0.8876, p < 0.001)
      respectively. Both PVI and SVV showed rapid and IAP correlative changes with
      increasing intra-abdominal pressure in patients undergoing laparoscopic
      cholecystectomy. 

PMID- 25971700
TI  - Do sequence-space synaesthetes have better spatial imagery skills? Yes, but there
      are individual differences.
AB  - People with sequence-space synaesthesia perceive sequences (e.g. numbers, months,
      letters) as spatially extended forms. Here, we ask whether sequence-space
      synaesthetes have advantages in visuo-spatial skills such as mental rotation.
      Previous studies addressing this question have produced mixed results with some
      showing mental rotation advantages (Simner et al. in Cortex 45:1246-1260, 2009;
      Brang et al. in Cogn Process, 2013), but one that did not (Rizza and Price in
      Cogn Process 13:299-303, 2012). We tested this hypothesis again with a new group
      of sequence-space synaesthetes, and we also tested a range of individual
      differences that might have caused this conflict across previous studies.
      Specifically, we tested: years of education, visual imagery ability, nature of
      forms (2D or 3D representation of sequences), number of forms (e.g. for months,
      days, numbers), and tendency to project sequences into external space versus the
      mind's eye. We found yet again that synaesthetes had enhanced abilities in mental
      rotation compared to controls, but that one individual difference in synaesthetes
      (the ability to project forms into space) was especially linked to performance.
      We also found that synaesthetes self-reported higher visual imagery than controls
      (Price in Cortex 45:1229-1245, 2009; Mann et al. in Conscious Cognit 18:619-627,
      2009; Rizza and Price 2012). Overall, our data support previous studies showing
      superior imagery reports (Price 2009) and mental rotation (Simner et al. 2009;
      Brang et al. 2013) in sequence-space synaesthetes, and we suggest that one
      previous failure to replicate (Rizza and Price 2012) might be explained by
      individual differences among synaesthetes recruited for testing. 

PMID- 25971701
TI  - Biology and biotechnology of hyaluronan.
AB  - The hyaluronan (HA) polymer is a critical component of extracellular matrix with
      a remarkable structure: is a linear and unbranched polymer without sulphate or
      phosphate groups. It is ubiquitous in mammals showing several biological
      functions, ranging from cell proliferation and migration to angiogenesis and
      inflammation. For its critical biological functions the amount of HA in tissues
      is carefully controlled by different mechanisms including covalent modification
      of the synthetic enzymes and epigenetic control of their gene expression. The
      concentration of HA is also critical in several pathologies including cancer,
      diabetes and inflammation. Beside these biological roles, the structural
      properties of HA allow it to take advantage of its capacity to form gels even at
      concentration of 1 % producing scaffolds with very promising applications in
      regenerative medicine as biocompatible material for advanced therapeutic uses. In
      this review we highlight the biological aspects of HA addressing the mechanisms
      controlling the HA content in tissues as well as its role in important human
      pathologies. In the second part of the review we highlight the different use of
      HA polymers in the modern biotechnology. 

PMID- 25971702
TI  - Glycan structure and serum half-life of recombinant CTLA4Ig, an immunosuppressive
      agent, expressed in suspension-cultured rice cells with coexpression of human
      beta1,4-galactosyltransferase and human CTLA4Ig.
AB  - Human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) is an
      immunosuppressive therapeutic, and recently produced rice cell-derived hCTLA4Ig
      (hCTLA4Ig(P)) reportedly exhibits in vitro immunosuppressive activities
      equivalent to those of Chinese hamster ovary cell-derived hCTLA4Ig (hCTLA4Ig(M)).
      However, limitations of hCTLA4Ig(P) include shortened in vivo half-life as well
      as the presence of nonhuman N-glycans containing (beta1-2)-xylose and alpha1,3
      fucose, which cause immunogenic reactions in humans. In the present study, human
      beta1,4-galactose-extended hCTLA4Ig(P) (hCTLA4Ig(P)-Gal) was expressed through
      the coexpression of human beta1,4-galactosyltransferase (hGalT) and hCTLA4Ig in
      an attempt to overcome these unfavorable effects. The results indicated that both
      encoding hGalT and hCTLA4Ig were successfully coexpressed, and the analysis of N
      glycan and its relative abundance in purified hCTLA4Ig(P)-Gal indicated that not
      only were the two glycans containing (beta1-4)-galactose newly extended, but also
      glycans containing both beta1,2-xylose and alpha1,3-fucose were markedly reduced
      and high-mannose-type glycans were increased compared to those of hCTLA4Ig(P),
      respectively. Unlike hCTLA4Ig(P), hCTLA4Ig(P)-Gal was effective as an acceptor
      via (beta1-4)-galactose for in vitro sialylation. Additionally, the serum half
      life of intravenously injected hCTLA4Ig(P)-Gal in Sprague-Dawley rats was 1.9
      times longer than that of hCTLA4Ig(P), and the clearance pattern of hCTLA4Ig(P)
      Gal was close to that for hCTLA4Ig(M). These results indicate that the
      coexpression with hGalT and hCTLA4Ig(P) is useful for both reducing glycan
      immunogens and increasing in vivo stability. This is the first report of hCTLA4Ig
      as an effective therapeutics candidate in glycoengineered rice cells. 

PMID- 25971705
TI  - Illuminating CO2 reduction on frustrated Lewis pair surfaces: investigating the
      role of surface hydroxides and oxygen vacancies on nanocrystalline In2O(3
      x)(OH)y.
AB  - Designing catalytic nanostructures that can thermochemically or photochemically
      convert gaseous carbon dioxide into carbon based fuels is a significant challenge
      which requires a keen understanding of the chemistry of reactants, intermediates
      and products on surfaces. In this context, it has recently been reported that the
      reverse water gas shift reaction (RWGS), whereby carbon dioxide is reduced to
      carbon monoxide and water, CO2 + H2 -> CO + H2O, can be catalysed by hydroxylated
      indium oxide nanocrystals, denoted In2O(3-x)(OH)y, more readily in the light than
      in the dark. The surface hydroxide groups and oxygen vacancies on In2O(3-x)(OH)y
      were both shown to assist this reaction. While this advance provides a first step
      toward the rational design and optimization of a single-component gas-phase CO2
      reduction catalyst for solar fuels generation, the precise role of the hydroxide
      groups and oxygen vacancies in facilitating the reaction on In2O(3-x)(OH)y
      nanocrystals has not been resolved. In the work reported herein, for the first
      time we present in situ spectroscopic and kinetic observations, complemented by
      density functional theory analysis, that together provide mechanistic information
      into the surface reaction chemistry responsible for the thermochemical and
      photochemical RWGS reaction. Specifically, we demonstrate photochemical CO2
      reduction at a rate of 150 MUmol gcat(-1) hour(-1), which is four times better
      than the reduction rate in the dark, and propose a reaction mechanism whereby a
      surface active site of In2O(3-x)(OH)y, composed of a Lewis base hydroxide
      adjacent to a Lewis acid indium, together with an oxygen vacancy, assists the
      adsorption and heterolytic dissociation of H2 that enables the adsorption and
      reaction of CO2 to form CO and H2O as products. This mechanism, which has its
      analogue in molecular frustrated Lewis pair (FLP) chemistry and catalysis of CO2
      and H2, is supported by preliminary kinetic investigations. The results of this
      study emphasize the importance of engineering the surfaces of nanostructures to
      facilitate gas-phase thermochemical and photochemical carbon dioxide reduction
      reactions to energy rich fuels at technologically significant rates.

PMID- 25971704
TI  - Identification of REST targets in the Xenopus tropicalis genome.
AB  - BACKGROUND: A major role of REST (repressor element-1 silencing transcription
      factor) is to inhibit the expression of neuronal genes in neural stem cells and
      non-neuronal cells by binding to a 21 bp consensus sequence and recruiting
      epigenetic and regulatory cofactors to gene regulatory regions. In neural stem
      cells, REST silences differentiation-promoting genes to prevent their premature
      expression and is central to the regulation of neurogenesis and the balance of
      neural stem cells and neurons. RESULTS: To understand the role of REST in
      vertebrate neurogenesis, we performed a genome-wide screen for REST targets in
      Xenopus tropicalis. We identified 742 neuron-restrictive silencer elements (NRSE)
      associated with 1396 genes that are enriched in neuronal function. Comparative
      analyses revealed that characteristics of NRSE motifs in frog are similar to
      those in mammals in terms of the distance to target genes, frequency of motifs
      and the repertoire of putative target genes. In addition, we identified four F
      box ubiquitin ligases as putative REST targets and determined that they are
      expressed in neuronal tissues during Xenopus development. CONCLUSION: We
      identified a conserved core of putative target genes in human, mouse and frog
      that may be fundamental to REST function in vertebrates. We demonstrate that NRSE
      sites are associated with both protein-coding genes and lncRNAs in the human
      genome. Furthermore, we demonstrate that REST binding sites are abundant in low
      gene-occupancy regions of the human genome but this is not due to an increased
      association with non-coding RNAs. Our findings identify novel targets of REST and
      broaden the known mechanism of REST-mediated silencing in neurogenesis.

PMID- 25971703
TI  - The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow
      mesenchymal stem cells in rats is related to cell dose and infusion velocity.
AB  - INTRODUCTION: Intra-arterial cell infusion is an efficient delivery route with
      which to target organs such as the ischemic brain. However, adverse events
      including microembolisms and decreased cerebral blood flow were recently reported
      after intra-arterial cell delivery in rodent models, raising safety concerns. We
      tested the hypothesis that cell dose, infusion volume, and velocity would be
      related to the severity of complications after intra-arterial cell delivery.
      METHODS: In this study, 38 rats were subjected to a sham middle cerebral artery
      occlusion (sham-MCAO) procedure before being infused with allogeneic bone-marrow
      mesenchymal stem cells at different cell doses (0 to 1.0 * 10(6)), infusion
      volumes (0.5 to 1.0 ml), and infusion times (3 to 6 minutes). An additional group
      (n = 4) was infused with 1.0 * 10(6) cells labeled with iron oxide for in vivo
      tracking of cells. Cells were infused through the external carotid artery under
      laser Doppler flowmetry monitoring 48 hours after sham-MCAO. Magnetic resonance
      imaging (MRI) was performed 24 hours after cell infusion to reveal cerebral
      embolisms or hemorrhage. Limb placing, cylinder, and open field tests were
      conducted to assess sensorimotor functions before the rats were perfused for
      histology. RESULTS: A cell dose-related reduction in cerebral blood flow was
      noted, as well as an increase in embolic events and concomitant lesion size, and
      sensorimotor impairment. In addition, a low infusion velocity (0.5 ml/6 minutes)
      was associated with high rate of complications. Lesions on MRI were confirmed
      with histology and corresponded to necrotic cell loss and blood-brain barrier
      leakage. CONCLUSIONS: Particularly cell dose but also infusion velocity
      contribute to complications encountered after intra-arterial cell
      transplantation. This should be considered before planning efficacy studies in
      rats and, potentially, in patients with stroke.

PMID- 25971706
TI  - Polytetrafluoroethylene fume-induced pulmonary edema: a case report and review of
      the literature.
AB  - INTRODUCTION: Polytetrafluoroethylene is ubiquitous in materials commonly used in
      cooking and industrial applications. Overheated polytetrafluoroethylene can
      generate toxic fumes, inducing acute pulmonary edema in some cases. However,
      neither the etiology nor the radiological features of this condition have been
      determined. For clarification, we report an illustrative case, together with the
      first comprehensive literature review. CASE PRESENTATION: A previously healthy 35
      year-old Japanese man who developed severe dyspnea presented to our hospital. He
      had left a polytetrafluoroethylene-coated pan on a gas-burning stove for 10 hours
      while unconscious. Upon admission, he was in severe respiratory distress. A chest
      computed tomographic scan showed massive bilateral patchy consolidations with
      ground-glass opacities and peripheral area sparing. A diagnosis of
      polytetrafluoroethylene fume-induced pulmonary edema was made. He was treated
      with non-invasive positive pressure ventilation and a neutrophil elastase
      inhibitor, which dramatically alleviated his symptoms and improved his
      oxygenation. He was discharged without sequelae on hospital day 11. A literature
      review was performed to survey all reported cases of polytetrafluoroethylene fume
      induced pulmonary edema. We searched the PubMed, Embase, Web of Science and
      OvidSP databases for reports posted between the inception of the databases and 30
      September 2014, as well as several Japanese databases (Ichushi Web, J-STAGE,
      Medical Online, and CiNii). Two radiologists independently interpreted all chest
      computed tomographic images. Eighteen relevant cases (including the presently
      reported case) were found. Our search revealed that (1) systemic inflammatory
      response syndrome was frequently accompanied by pulmonary edema, and (2) common
      computed tomography findings were bilateral ground-glass opacities, patchy
      consolidation and peripheral area sparing. Pathophysiological and radiological
      features were consistent with the exudative phase of acute respiratory distress
      syndrome. However, the contrast between the lesion and the spared peripheral area
      was striking and was distinguishable from the common radiological features of
      acute respiratory distress syndrome. CONCLUSION: The essential etiology of
      polytetrafluoroethylene fume-induced pulmonary edema seems to be increased
      pulmonary vascular permeability caused by an inflammatory response to the toxic
      fumes. The radiological findings that distinguish polytetrafluoroethylene fume
      induced pulmonary edema can be bilateral ground-glass opacity or a patchy
      consolidation with clear sparing of the peripheral area.

PMID- 25971707
TI  - Statistical analysis and handling of missing data in cluster randomised trials:
      protocol for a systematic review.
AB  - INTRODUCTION: Cluster randomised trials (CRTs) randomise participants in groups,
      rather than as individuals, and are key tools used to assess interventions in
      health research where treatment contamination is likely or if individual
      randomisation is not feasible. Missing outcome data can reduce power in trials,
      including in CRTs, and is a potential source of bias. The current review focuses
      on evaluating methods used in statistical analysis and handling of missing data
      with respect to the primary outcome in CRTs. METHODS AND ANALYSIS: We will search
      for CRTs published between August 2013 and July 2014 using PubMed, Web of Science
      and PsycINFO. We will identify relevant studies by screening titles and
      abstracts, and examining full-text articles based on our predefined study
      inclusion criteria. 86 studies will be randomly chosen to be included in our
      review. Two independent reviewers will collect data from each study using a
      standardised, prepiloted data extraction template. Our findings will be
      summarised and presented using descriptive statistics. ETHICS AND DISSEMINATION:
      This methodological systematic review does not need ethical approval because
      there are no data used in our study that are linked to individual patient data.
      After completion of this systematic review, data will be immediately analysed,
      and findings will be disseminated through a peer-reviewed publication and
      conference presentation.

PMID- 25971709
TI  - Adolescent-to-Parent Abuse as a Form of "Domestic Violence": A Conceptual Review.
AB  - Across the Global North, adolescent-to-parent abuse (APA) is becoming recognized
      as a significant social problem and is receiving attention from researchers,
      policymakers, and practitioners who work in the intersecting fields of juvenile
      justice, child protection, and domestic violence. One of the key questions
      shaping current debates concerns the extent to which APA maps onto the contours
      of domestic violence, in terms of research and theory, policy, and practice. In
      particular, to what extent can our established ways of working with domestic
      violence be applied when working with APA? This article begins by reviewing
      definitions and prevalence rates of APA. It then considers how the problem fits
      into the "family conflicts" and "gender-based violence" paradigms that are most
      frequently used to conceptualize domestic violence. The article then examines how
      APA represents a similar but distinct phenomenon to adult-instigated domestic
      violence and identifies how its departures represent particular challenges in
      working toward its elimination. The article concludes by reviewing intervention
      programs that work with APA and exploring some of the ways in which they adopt
      and reject elements of good practice from the domestic violence practice field.

PMID- 25971708
TI  - A population-based study comparing patterns of care delivery on the quality of
      care for persons living with HIV in Ontario.
AB  - OBJECTIVES: Physician specialty is often positively associated with disease
      specific outcomes and negatively associated with primary care outcomes for people
      with chronic conditions. People with HIV have increasing comorbidity arising from
      antiretroviral therapy (ART) related longevity, making HIV a useful condition to
      examine shared care models. We used a previously described, theoretically
      developed shared care framework to assess the impact of care delivery on the
      quality of care provided. DESIGN: Retrospective population-based observational
      study from 1 April 2009 to 31 March 2012. PARTICIPANTS: 13 480 patients with HIV
      and receiving publicly funded healthcare in Ontario were assigned to one of five
      patterns of care. OUTCOME MEASURES: Cancer screening, ART prescribing and
      healthcare utilisation across models using adjusted multivariable hierarchical
      logistic regression analyses. RESULTS: Models in which patients had an assigned
      family physician had higher odds of cancer screening than those in exclusively
      specialist care (colorectal cancer screening, exclusively primary care adjusted
      OR (AOR)=3.12, 95% CI (1.90 to 5.13), family physician-dominant co-management
      AOR=3.39, 95% CI (1.94 to 5.93), specialist-dominant co-management AOR=2.01, 95%
      CI (1.23 to 3.26)). The odds of having one emergency department visit did not
      differ among models, although the odds of hospitalisation and HIV-specific
      hospitalisation were lower among patients who saw exclusively family physicians
      (AOR=0.23, 95% CI (0.14 to 0.35) and AOR=0.15, 95% CI (0.12 to 0.21)). The odds
      of antiretroviral prescriptions were lower among models in which patients' HIV
      care was provided predominantly by family physicians (exclusively primary care
      AOR=0.15, 95% CI (0.12 to 0.21), family physician-dominant co-management
      AOR=0.45, 95% CI (0.32 to 0.64)). CONCLUSIONS: How care is provided had a
      potentially important influence on the quality of care delivered. Our key
      limitation is potential confounding due to the absence of HIV stage measures.

PMID- 25971710
TI  - Evidence for the Efficacy of the Child Advocacy Center Model: A Systematic
      Review.
AB  - The Child Advocacy Center (CAC) model has been presented as the solution to many
      of the problems inherent in responses by authorities to child sexual abuse. The
      lack of referral to therapeutic services and support, procedurally flawed and
      potentially traumatic investigation practices, and conflict between the different
      statutory agencies involved are all thought to contribute to low conviction rates
      for abuse and poor outcomes for children. The CAC model aims to address these
      problems through a combination of multidisciplinary teams, joint investigations,
      and services, all provided in a single child friendly environment. Using a
      systematic search strategy, this research aimed to identify and review all
      studies that have evaluated the effectiveness of the approach as a whole,
      recognizing that a separate evidence base exists for parts of the approach (e.g.,
      victim advocacy and therapeutic responses). The review found that while the
      criminal justice outcomes of the model have been well studied, there was a lack
      of research on the effect of the model on child and family outcomes. Although
      some modest outcomes were clear, the lack of empirical research, and overreliance
      on measuring program outputs, rather than outcomes, suggests that some
      clarification of the goals of the CAC model is needed.

PMID- 25971712
TI  - Self assembly of magnetic nanoparticles at silicon surfaces.
AB  - Neutron reflectometry was used to study the assembly of magnetite nanoparticles
      in a water-based ferrofluid close to a silicon surface. Under three conditions,
      static, under shear and with a magnetic field, the depth profile is extracted.
      The particles have an average diameter of 11 nm and a volume density of 5% in a
      D2O-H2O mixture. They are surrounded by a 4 nm thick bilayer of carboxylic acid
      for steric repulsion. The reflectivity data were fitted to a model using a least
      square routine based on the Parratt formalism. From the scattering length density
      depth profiles the following behavior is concluded: the fits indicate that excess
      carboxylic acid covers the silicon surface and almost eliminates the water in the
      densely packed wetting layer that forms close to the silicon surface. Under
      constant shear the wetting layer persists but a depletion layer forms between the
      wetting layer and the moving ferrofluid. Once the flow is stopped, the wetting
      layer becomes more pronounced with dense packing and is accompanied by a looser
      packed second layer. In the case of an applied magnetic field the prolate
      particles experience a torque and align with their long axes along the silicon
      surface which leads to a higher particle density. 

PMID- 25971711
TI  - A NK complex-linked locus restricts the spread of herpes simplex virus type 1 in
      the brains of C57BL/6 mice.
AB  - The most frequent cause of sporadic viral encephalitis in western countries is
      Herpes simplex virus (HSV). Despite treatment, mortality rates reach 20-30% while
      survivors often suffer from significant morbidity. In mice, resistance to lethal
      Herpes simplex encephalitis (HSE) is multifactorial and influenced by mouse and
      virus strain as well as route of infection. The ability to restrict viral spread
      in the brain is one factor contributing to resistance. After infection of the
      oral mucosa with HSV type 1 (HSV-1), virus spreads throughout the brains of
      susceptible strains but is restricted in resistant C57BL/6 mice. To further
      investigate restriction of viral spread in the brain, mendelian analysis was
      combined with studies of congenic, intra-natural killer complex (intra-NKC)
      recombinant and antibody-depleted mice. Results from mendelian analysis support
      the restriction of viral spread as a dominant trait and consistent with a single
      gene effect. In congenic mice, the locus maps to the NKC on chromosome 6 and is
      provisionally termed Herpes Resistance Locus 2 (Hrl2). In intra-NKC recombinants,
      the locus is further mapped to the segment Cd69 through D6Wum34; a different
      location from previously identified loci (Hrl and Rhs1) also associated with HSV
      1 infection. Studies with antibody-depleted mice indicate the effect of this
      locus is mediated by NK1.1(+) expressing cells. This model increases our
      knowledge of lethal HSE, which may lead to new treatment options. 

PMID- 25971713
TI  - Use of second- and third-generation tyrosine kinase inhibitors in the treatment
      of chronic myeloid leukemia: an evolving treatment paradigm.
AB  - Although imatinib remains the gold standard for first-line treatment of chronic
      myeloid leukemia (CML), increasing recognition of imatinib resistance and
      intolerance has led to the development of additional tyrosine kinase inhibitors
      (TKIs), which have demonstrated effectiveness as salvage therapies or alternative
      first-line treatments. Although additional options represent progress, the
      availability of 3 second-generation TKIs (dasatinib, nilotinib, and bosutinib)
      and 1 third-generation TKI (ponatinib) has added complexity to the treatment
      paradigm for CML, particularly CML in the chronic phase. Two second-generation
      agents (dasatinib and nilotinib) are approved for use as first-line and
      subsequent therapy. Thus, the appropriate sequencing of TKIs is a frequent
      quandary, and is incompletely addressed in clinical guidelines. Here, we review
      studies that might guide selection of a second- or third-generation TKI after
      failure of TKI therapy in patients with chronic-phase CML. These studies evaluate
      prognostic factors such as first-line cytogenetic response and BCR-ABL1 mutation
      status, which might help physicians identify patients who are likely to respond
      to second-generation TKIs, and those for whom ponatinib or an investigational
      agent might be more appropriate. We summarize evidence to date that suggests that
      use of a second-generation TKI as third-line therapy confers limited value in
      most CML patients, and we also explore the utility of current event-free survival
      versus traditional outcomes to predict long-term benefits of sequential TKI use.
      Finally, we present 3 case studies to illustrate how prognostic factors and other
      considerations (eg, tolerability) can be used to individualize subsequent therapy
      in cases of TKI resistance or intolerance. 

PMID- 25971714
TI  - Physiological variability in volatile organic compounds (VOCs) in exhaled breath
      and released from faeces due to nutrition and somatic growth in a standardized
      caprine animal model.
AB  - Physiological effects may change volatile organic compound (VOC) concentrations
      and may therefore act as confounding factors in the definition of VOCs as disease
      biomarkers. To evaluate the extent of physiological background variability, this
      study assessed the effects of feed composition and somatic growth on VOC patterns
      in a standardized large animal model. Fifteen clinically healthy goats were
      followed during their first year of life. VOCs present in the headspace over
      faeces, exhaled breath and ambient air inside the stable were repeatedly assessed
      in parallel with the concentrations of glucose, protein, and albumin in venous
      blood. VOCs were collected and analysed using solid-phase or needle-trap
      microextraction and gas chromatograpy together with mass spectroscopy. The
      concentrations of VOCs in exhaled breath and above faeces varied significantly
      with increasing age of the animals. The largest variations in volatiles detected
      in the headspace over faeces occurred with the change from milk feeding to plant
      based diet. VOCs above faeces and in exhaled breath correlated significantly with
      blood components. Among VOCs exhaled, the strongest correlations were found
      between exhaled nonanal concentrations and blood concentrations of glucose and
      albumin. Results stress the importance of a profound knowledge of the
      physiological backgrounds of VOC composition before defining reliable and
      accurate marker sets for diagnostic purposes. 

PMID- 25971715
TI  - First-trimester maternal protein intake and childhood kidney outcomes: the
      Generation R Study.
AB  - BACKGROUND: Nutritional exposures during in utero development may have long
      lasting consequences for postnatal renal health. Animal studies suggest that
      specifically maternal dietary protein intake during pregnancy influences
      childhood kidney function. OBJECTIVE: We examined the associations of total,
      animal, and vegetable maternal protein intake during pregnancy with kidney volume
      and function in school-aged children. DESIGN: This study was conducted in 3650
      pregnant women and their children who were participating in a population-based
      cohort study from early life onward. First-trimester energy-adjusted maternal
      protein intake was assessed with a food-frequency questionnaire. At the child's
      age of 6 y, we assessed kidney volume, estimated glomerular filtration rate
      (eGFR) using serum creatinine and cystatin C concentrations, and microalbuminuria
      using urine albumin:creatinine ratios. RESULTS: First-trimester maternal total
      protein intake was associated with a higher childhood creatinine-based eGFR
      (difference: 0.06 mL * min(-1) * 1.73 m(-2); 95% CI: 0.01, 0.12 mL . min(-1) .
      1.73 m(-2) per gram of protein intake). This association was mainly driven by
      vegetable protein intake (0.22 mL * min(-1) * 1.73 m(-2); 95% CI: 0.10, 0.35 mL .
      min(-1) . 1.73 m(-2) per gram of vegetable protein intake). These associations
      were not explained by protein intake in early childhood. First-trimester maternal
      protein intake was not significantly associated with childhood kidney volume,
      cystatin C-based eGFR, or the risk of microalbuminuria. CONCLUSIONS: Our findings
      suggest that higher total and vegetable, but not animal, maternal protein intake
      during the first trimester of pregnancy is associated with a higher eGFR in
      childhood. Further follow-up studies are needed to investigate whether maternal
      protein intake in early pregnancy also affects the risk of kidney diseases in
      later life.

PMID- 25971716
TI  - Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer.
AB  - BACKGROUND: Vitamin D status might be associated with cancer survival. Survival
      after ovarian cancer is poor, but the association with vitamin D has rarely been
      examined. OBJECTIVE: We evaluated the association between serum 25-hydroxyvitamin
      D [25(OH)D], a marker of vitamin D status, and ovarian cancer survival. DESIGN:
      Participants were women with invasive ovarian cancer diagnosed between 2002 and
      2005 who participated in the Australian Ovarian Cancer Study. Serum samples,
      collected at diagnosis (n = 670) or after completion of primary treatment and
      before recurrence (n = 336), were assayed for 25(OH)D. Sociodemographic, dietary,
      and lifestyle data came from questionnaires self-completed at recruitment, and
      clinical and survival data were from medical records, supplemented by linkage to
      the Australian National Death Index (October 2011). Cox proportional hazards
      regression was used to estimate HRs and 95% CIs for the association between
      circulating 25(OH)D and survival. RESULTS: Overall, 59% of the women died during
      follow-up, with 95% of deaths resulting from ovarian cancer. Circulating 25(OH)D
      concentrations (mean: 44 nmol/L) were significantly associated with age, state of
      residence, season of blood collection, and body mass index but not with tumor
      histology, stage or grade, or comorbidities. Higher 25(OH)D concentrations at
      diagnosis were significantly associated with longer survival (adjusted HR: 0.93;
      95% CI: 0.88, 0.99 per 10 nmol/L), but there was no significant association with
      progression-free survival or for 25(OH)D measured after primary treatment.
      CONCLUSIONS: In our cohort, higher serum 25(OH)D concentrations at diagnosis were
      associated with longer survival among women with ovarian cancer. If confirmed in
      other studies, this suggests that vitamin D status at diagnosis may be an
      independent predictor of prognosis. Furthermore, if the association is found to
      be causal, improving vitamin D status may improve ovarian cancer survival rates.

PMID- 25971717
TI  - Identifying cardiovascular risk factor-related dietary patterns with reduced rank
      regression and random forest in the EPIC-NL cohort.
AB  - BACKGROUND: Several methods are used to determine dietary patterns. Hybrid
      methods incorporate information on nutrient intake or biological factors to
      extract patterns relevant to disease etiology. OBJECTIVE: We explore differences
      between patterns derived with 2 hybrid methods with those obtained by a
      posteriori methods and compare associations of these patterns with coronary
      artery disease (CAD) and stroke risk. DESIGN: Food-frequency questionnaires were
      used to estimate dietary intake in 34,644 participants of European Prospective
      Investigation into Cancer-Netherlands at baseline (1993-1997). Follow-up was
      complete until 31 December 2007. Hybrid methods to determine dietary patterns
      were reduced rank regression (RRR) and random forest with classification tree
      analysis (RF-CTA). Included risk factors were body mass index, total:high-density
      lipoprotein cholesterol ratio, and systolic blood pressure. Results were compared
      with those from principal component analysis (PCA) and k-means cluster analysis
      (KCA), respectively. RESULTS: Both RRR and PCA derived a "Western," "prudent,"
      and "traditional pattern." All RRR patterns were significantly associated with
      CAD risk [highest vs. lowest quartile factor score; HR: 1.45 (95% CI: 1.25,
      1.69), 0.86 (0.74, 0.99), and 1.25 (1.07, 1.47), respectively]. Only the prudent
      RRR factor was statistically significant associated with stroke (HR: 0.76; 95%
      CI: 0.59, 0.97). From the PCA patterns, only the traditional pattern was
      associated with CAD (HR: 1.29; 95% CI: 1.11, 1.50). RF-CTA derived 7 dietary
      patterns that could be categorized as "Western-like," "prudent-like," and
      "traditional-like." KCA established a prudent and Western cluster. Compared with
      the RF-CTA "prudent-like 1" pattern, only the "traditional-like 1" pattern was
      associated with CAD (HR: 1.36; 955 CI: 1.12, 1.65). None of the RF-CTA groups
      were associated with stroke. Compared with the Western KCA cluster, the prudent
      cluster was not associated with CAD or stroke. CONCLUSION: Including risk factors
      in RRR and RF-CTA resulted in small differences in food groups, contributing to
      similar patterns that showed in general stronger associations with CAD than PCA
      and KCA, respectively.

PMID- 25971718
TI  - The conundrum of whole foods versus macronutrient composition in assessing
      effects on insulin sensitivity.

PMID- 25971719
TI  - Evaluation of various biomarkers as potential mediators of the association
      between Delta5 desaturase, Delta6 desaturase, and stearoyl-CoA desaturase
      activity and incident type 2 diabetes in the European Prospective Investigation
      into Cancer and Nutrition-Potsdam Study.
AB  - BACKGROUND: An association between desaturase activity and risk of type 2
      diabetes (T2D) has been found in epidemiologic studies, but little is known about
      potential mediators of this association. OBJECTIVE: We aimed to investigate the
      potential role of diabetes-related biomarkers as mediators of the association
      between estimated Delta5 desaturase (D5D), Delta6 desaturase (D6D), and stearoyl
      CoA desaturase (SCD) activity and T2D risk. DESIGN: We analyzed a case-cohort
      study (subcohort: n = 1533; verified incident T2D cases: n = 400), nested within
      the European Prospective Investigation into Cancer and Nutrition-Potsdam Study
      involving 27,548 middle-aged participants. We evaluated the impact of adjustment
      for several T2D-related biomarkers reflecting liver fat accumulation [reflected
      by gamma-glutamyltransferase (GGT), alanine transaminase (ALT), fetuin-A, and the
      algorithm-based fatty liver index (FLI)], dyslipidemia (high-density lipoprotein
      cholesterol, triglycerides), inflammation [C-reactive protein (CRP)], and
      adiponectin on the association between D5D, D6D, and SCD activity, estimated with
      fatty acid product-to-precursor ratios derived from erythrocyte membrane
      proportions, and T2D risk. RESULTS: Estimated D5D activity was inversely
      associated with T2D risk, whereas D6D and SCD activities were positively
      associated with risk of T2D [HRs (95% CIs) (highest vs. lowest tertile): 0.51
      (0.36, 0.73), 1.68 (1.18, 2.39), and 1.82 (1.29, 2.58), respectively]. The
      association between estimated D5D, D6D, and SCD activities and risk of T2D was
      statistically significantly and markedly attenuated after adjustment for the FLI
      and, to a lesser extent, after adjustment for triglycerides, whereas adjustment
      for other desaturase-associated biomarkers (CRP, fetuin-A, ALT, and GGT) did not
      lead to appreciable attenuations. CONCLUSIONS: Liver fat accumulation, as
      reflected by the FLI, and dyslipidemia, as reflected by triglycerides, may partly
      explain the association between estimated D5D, D6D, and SCD activity and T2D
      risk.

PMID- 25971720
TI  - Bringing clarity to the role of MTHFR variants in neural tube defect prevention.

PMID- 25971721
TI  - Adequate enteral protein intake is inversely associated with 60-d mortality in
      critically ill children: a multicenter, prospective, cohort study.
AB  - BACKGROUND: The impact of protein intake on outcomes in pediatric critical
      illness is unclear. OBJECTIVE: We examined the association between protein intake
      and 60-d mortality in mechanically ventilated children. DESIGN: In a prospective,
      multicenter, cohort study that included 59 pediatric intensive care units (PICUs)
      from 15 countries, we enrolled consecutive children (age: 1 mo to 18 y) who were
      mechanically ventilated for >=48 h. We recorded the daily and cumulative mean
      adequacies of energy and protein delivery as a percentage of the prescribed daily
      goal during the PICU stay <=10 d. We examined the association of the adequacy of
      protein delivery with 60-d mortality and determined variables that predicted
      protein intake adequacy. RESULTS: We enrolled 1245 subjects (44% female) with a
      median age of 1.7 y (IQR: 0.4, 7.0 y). A total of 985 subjects received enteral
      nutrition, 354 (36%) of whom received enteral nutrition via the postpyloric
      route. Mean +/- SD prescribed energy and protein goals were 69 +/- 28 kcal/kg per
      day and 1.9 +/- 0.7 g/kg per day, respectively. The mean delivery of enteral
      energy and protein was 36 +/- 35% and 37 +/- 38%, respectively, of the prescribed
      goal. The adequacy of enteral protein intake was significantly associated with 60
      d mortality (P < 0.001) after adjustment for disease severity, site, PICU days,
      and energy intake. In relation to mean enteral protein intake <20%, intake >=60%
      of the prescribed goal was associated with an OR of 0.14 (95% CI: 0.04, 0.52; P =
      0.003) for 60-d mortality. Early initiation, postpyloric route, shorter
      interruptions, larger PICU size, and a dedicated dietitian in the PICU were
      associated with higher enteral protein delivery. CONCLUSIONS: Delivery of >60% of
      the prescribed protein intake is associated with lower odds of mortality in
      mechanically ventilated children. Optimal prescription and modifiable practices
      at the bedside might enhance enteral protein delivery in the PICU with a
      potential for improved outcomes. This trial was registered at clinicaltrials.gov
      as NCT02354521.

PMID- 25971722
TI  - Diaphragm ultrasound in amyotrophic lateral sclerosis and other neuromuscular
      disorders.

PMID- 25971723
TI  - Ultrasound for assessment of diaphragm in ALS.
AB  - OBJECTIVE: To evaluate the correlation between diaphragm thickness assessed by
      ultrasound (US) with respiratory function tests and the diaphragm motor
      responses, in patients with amyotrophic lateral sclerosis (ALS). METHODS: 42
      consecutive ALS patients were studied (11 with bulbar-onset), excluding patients
      with marked orofacial paresis. Investigation included: revised ALS functional
      rating scale (ALSFRS-R), forced vital capacity (FVC), maximal voluntary
      ventilation (MVV), maximal inspiratory (MIP) and expiratory (MEP) pressures,
      nasal inspiratory pressure during sniff (SNIP); peak-to-peak amplitude of the
      diaphragmatic motor response to phrenic nerve stimulation (Diaphragm-CMAP),
      diaphragmatic thickness measured by ultrasound during maximal inspiration and
      during maximal expiration. Patients were analysed in bulbar or spinal subgroups.
      Correlations and multiple linear regression models were studied. RESULTS: The
      mean age at disease onset was 58.4 +/- 11.1 years and with a mean disease
      duration of 17.8 +/- 13.6 months. Ultrasound studies of diaphragm thickness in
      full inspiration correlated with diaphragm CMAP in the whole population and in
      spinal-onset patients; and were similar in the two groups. Multiple linear
      modelling showed that FVC, SNIP and MVV were dependent on the change of thickness
      (p=0.001, 0.001 and 0.020, respectively) and that MIP and MEP were related to
      diaphragm CMAP p=0.003 and p=0.025, respectively). CONCLUSION: Diaphragm
      thickness correlates with Diaphragm-CMAP, except in bulbar-onset patients.
      Respiratory tests are dependent on both diaphragm thickness and Diaphragm-CMAP.
      SIGNIFICANCE: US thickness of the diaphragm correlates with the number of
      functional motor units as assessed by the phrenic nerve motor amplitude.

PMID- 25971724
TI  - Conduction block in thoracic outlet syndrome? The need for motor root
      stimulation.

PMID- 25971725
TI  - Comparative effectiveness of everolimus-based therapy versus endocrine
      monotherapy among postmenopausal women with HR+/HER2- metastatic breast cancer: a
      retrospective chart review in community oncology practices in the US.
AB  - BACKGROUND: Everolimus-based therapy and endocrine monotherapy are used among
      postmenopausal women with hormone receptor-positive human epidermal growth factor
      receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) whose disease
      progressed or recurred on a non-steroidal aromatase inhibitor (NSAI). However,
      limited evidence exists regarding the real-world comparative effectiveness of
      these agents. METHODS: This retrospective chart review examined postmenopausal
      HR+/HER2- mBC patients in community-based oncology practices who received
      everolimus-based therapy or endocrine monotherapy (index therapy) as any line of
      therapy for mBC between 1 July 2012 and 15 April 2013 after NSAI failure. Time on
      treatment (TOT), progression-free survival (PFS), and time to chemotherapy (TTC)
      from index therapy initiation were compared using Kaplan-Meier analyses and Cox
      proportional hazards models adjusting for baseline characteristics. RESULTS: A
      total of 243 and 270 patients received everolimus-based therapy or endocrine
      monotherapy in a quota-based sample. Patients treated with everolimus-based
      therapy had a higher proportion of visceral metastases, high tumor burden, and
      use of prior chemotherapies for mBC. After adjusting for baseline
      characteristics, everolimus-based therapy was associated with significantly
      longer TOT (HR = 0.67, 95% CI: 0.51-0.87) and PFS (HR = 0.75, 95% CI: 0.57-0.98)
      than endocrine monotherapy. No significant difference was found between
      everolimus-based therapy and endocrine monotherapy in TTC (HR = 0.81, 95% CI:
      0.52-1.27). Results stratified by line of therapy were generally consistent with
      the overall results. LIMITATIONS: Limitations include recall and information bias
      with potentially absent or erroneous chart data, unobserved factors due to non
      randomization, inability to measure outcome assessments paired with measuring
      outcomes prior to exposures, and potential patient selection bias associated with
      chart review. CONCLUSIONS: Among a nationwide sample of postmenopausal HR+/HER2-
      mBC patients treated in community oncology settings, treatment with everolimus
      based therapy was associated with significantly longer TOT and PFS compared to
      endocrine monotherapy.

PMID- 25971726
TI  - Protein MRI contrast agent with unprecedented metal selectivity and sensitivity
      for liver cancer imaging.
AB  - With available MRI techniques, primary and metastatic liver cancers that are
      associated with high mortality rates and poor treatment responses are only
      diagnosed at late stages, due to the lack of highly sensitive contrast agents
      without Gd(3+) toxicity. We have developed a protein contrast agent (ProCA32)
      that exhibits high stability for Gd(3+) and a 10(11)-fold greater selectivity for
      Gd(3+) over Zn(2+) compared with existing contrast agents. ProCA32, modified from
      parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol(-1)?s(-1)/89.2 mmol(
      1)?s(-1) per particle). Using T1- and T2-weighted, as well as T2/T1 ratio
      imaging, we have achieved, for the first time (to our knowledge), robust MRI
      detection of early liver metastases as small as ~0.24 mm in diameter, much
      smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32
      exhibits appropriate in vivo preference for liver sinusoidal spaces and
      pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for
      noninvasive early detection of primary and metastatic liver cancers as well as
      for monitoring treatment and guiding therapeutic interventions, including drug
      delivery. 

PMID- 25971727
TI  - Effect of sialylation on EGFR phosphorylation and resistance to tyrosine kinase
      inhibition.
AB  - Epidermal growth factor receptor (EGFR) is a heavily glycosylated transmembrane
      receptor tyrosine kinase. Upon EGF-binding, EGFR undergoes conformational changes
      to dimerize, resulting in kinase activation and autophosphorylation and
      downstream signaling. Tyrosine kinase inhibitors (TKIs) have been used to treat
      lung cancer by inhibiting EGFR phosphorylation. Previously, we demonstrated that
      EGFR sialylation suppresses its dimerization and phosphorylation. In this report,
      we further investigated the effect of sialylation on the phosphorylation profile
      of EGFR in TKI-sensitive and TKI-resistant cells. Sialylation was induced in
      cancer progression to inhibit the association of EGFR with EGF and the subsequent
      autophosphorylation. In the absence of EGF the TKI-resistant EGFR mutant
      (L858R/T790M) had a higher degree of sialylation and phosphorylation at Y1068,
      Y1086, and Y1173 than the TKI-sensitive EGFR. In addition, although sialylation
      in the TKI-resistant mutants suppresses EGFR tyrosine phosphorylation, with the
      most significant effect on the Y1173 site, the sialylation effect is not strong
      enough to stop cancer progression by inhibiting the phosphorylation of these
      three sites. These findings were supported further by the observation that the
      L858R/T790M EGFR mutant, when treated with sialidase or sialyltransferase
      inhibitor, showed an increase in tyrosine phosphorylation, and the sensitivity of
      the corresponding resistant lung cancer cells to gefitinib was reduced by
      desialylation and was enhanced by sialylation. 

PMID- 25971728
TI  - Postmitotic regulation of sensory area patterning in the mammalian neocortex by
      Lhx2.
AB  - Current knowledge suggests that cortical sensory area identity is controlled by
      transcription factors (TFs) that specify area features in progenitor cells and
      subsequently their progeny in a one-step process. However, how neurons acquire
      and maintain these features is unclear. We have used conditional inactivation
      restricted to postmitotic cortical neurons in mice to investigate the role of the
      TF LIM homeobox 2 (Lhx2) in this process and report that in conditional mutant
      cortices area patterning is normal in progenitors but strongly affected in
      cortical plate (CP) neurons. We show that Lhx2 controls neocortical area
      patterning by regulating downstream genetic and epigenetic regulators that drive
      the acquisition of molecular properties in CP neurons. Our results question a
      strict hierarchy in which progenitors dominate area identity, suggesting a novel
      and more comprehensive two-step model of area patterning: In progenitors,
      patterning TFs prespecify sensory area blueprints. Sequentially, sustained
      function of alignment TFs, including Lhx2, is essential to maintain and to
      translate the blueprints into functional sensory area properties in cortical
      neurons postmitotically. Our results reemphasize critical roles for Lhx2 that
      acts as one of the terminal selector genes in controlling principal properties of
      neurons. 

PMID- 25971729
TI  - Influence of three-dimensional nanoparticle branching on the Young's modulus of
      nanocomposites: Effect of interface orientation.
AB  - With the availability of nanoparticles with controlled size and shape, there has
      been renewed interest in the mechanical properties of polymer/nanoparticle
      blends. Despite the large number of theoretical studies, the effect of branching
      for nanofillers tens of nanometers in size on the elastic stiffness of these
      composite materials has received limited attention. Here, we examine the Young's
      modulus of nanocomposites based on a common block copolymer (BCP) blended with
      linear nanorods and nanoscale tetrapod Quantum Dots (tQDs), in electrospun fibers
      and thin films. We use a phenomenological lattice spring model (LSM) as a guide
      in understanding the changes in the Young's modulus of such composites as a
      function of filler shape. Reasonable agreement is achieved between the LSM and
      the experimental results for both nanoparticle shapes--with only a few key
      physical assumptions in both films and fibers--providing insight into the design
      of new nanocomposites and assisting in the development of a qualitative
      mechanistic understanding of their properties. The tQDs impart the greatest
      improvements, enhancing the Young's modulus by a factor of 2.5 at 20 wt.%. This
      is 1.5 times higher than identical composites containing nanorods. An unexpected
      finding from the simulations is that both the orientation of the nanoscale filler
      and the orientation of X-type covalent bonds at the nanoparticle-ligand interface
      are important for optimizing the mechanical properties of the nanocomposites. The
      tQD provides an orientational optimization of the interfacial and filler bonds
      arising from its three-dimensional branched shape unseen before in nanocomposites
      with inorganic nanofillers.

PMID- 25971730
TI  - Giant thermal spin-torque-assisted magnetic tunnel junction switching.
AB  - Spin-polarized charge currents induce magnetic tunnel junction (MTJ) switching by
      virtue of spin-transfer torque (STT). Recently, by taking advantage of the spin
      dependent thermoelectric properties of magnetic materials, novel means of
      generating spin currents from temperature gradients, and their associated thermal
      spin torques (TSTs), have been proposed, but so far these TSTs have not been
      large enough to influence MTJ switching. Here we demonstrate significant TSTs in
      MTJs by generating large temperature gradients across ultrathin MgO tunnel
      barriers that considerably affect the switching fields of the MTJ. We attribute
      the origin of the TST to an asymmetry of the tunneling conductance across the
      zero-bias voltage of the MTJ. Remarkably, we estimate through magneto-Seebeck
      voltage measurements that the charge currents that would be generated due to the
      temperature gradient would give rise to STT that is a thousand times too small to
      account for the changes in switching fields that we observe. 

PMID- 25971731
TI  - Adolescent first births in East Africa: disaggregating characteristics, trends
      and determinants.
AB  - BACKGROUND: The use of a single national figure fails to capture the complex
      patterns and inequalities in early childbearing that occur within countries, as
      well as the differing contexts in which these pregnancies occur. Further
      disaggregated data that examine patterns and trends for different groups are
      needed to enable programmes to be focused on those most at risk. This paper
      describes a comprehensive analysis of adolescent first births using disaggregated
      data from Demographic and Household surveys (DHS) for three East African
      countries: Uganda, Kenya and Tanzania. METHODS: The study initially produces
      cross-sectional descriptive data on adolescent motherhood by age (under 16, 16-17
      and 18-19 years), marital status, wealth, education, state or region, urban/rural
      residence and religion. Trends for two or more surveys over a period of 18-23
      years are then analysed, and again disaggregated by age, wealth, urban/rural
      residence and marital status to ascertain which groups within the population have
      benefited most from reductions in adolescent first birth. In order to adjust for
      confounding factors we also use multinomial logistic regression to analyse the
      social and economic determinants of adolescent first birth, with outcomes again
      divided by age. FINDINGS: In all three countries, a significant proportion of
      women gave birth before age 16 (7%-12%). Both the bivariate analysis and logistic
      regression show that adolescent motherhood is strongly associated with poverty
      and lack of education/literacy, and this relationship is strongest among births
      within the youngest age group (<16 years). There are also marked differences by
      region, religion and urban/rural residence. Trends over time show there has been
      limited progress in reducing adolescent first births overall, with no reductions
      among the poorest. CONCLUSIONS: Adolescent first births, particularly at the
      youngest ages, are most common among the poorest and least educated, and progress
      in reducing rates within this group has not been made over the last few decades.
      Disaggregating data allows such patterns to be understood, and enables efforts to
      be better directed where needed.

PMID- 25971732
TI  - Fast Water Diffusion and Long-Term Polymer Reorganization during Nafion Membrane
      Hydration Evidenced by Time-Resolved Small-Angle Neutron Scattering.
AB  - We report a small-angle neutron scattering study of liquid water sorption in
      Nafion membranes. The swelling of hydrophilic domains was measured on the
      nanoscale by combining in situ time-resolved and long-term static experiments,
      yielding kinetic curves recorded over an unprecedented time scale, from hundreds
      of milliseconds to several years. At low water content, typically below 5 water
      molecules per ionic group, a limited subdiffusive regime was observed and
      ascribed to nanoconfinement and local interactions between charged species and
      water molecules. Further ultrafast and thermally activated swelling due to
      massive liquid water sorption was observed and analyzed by using Fick's equation.
      The extracted mutual water diffusion coefficients are in good agreement with
      pulsed field gradient NMR self-diffusion coefficient values, evidencing a water
      diffusion-driven process due to concentration gradients within the Nafion
      membrane. Finally, after completion of the ultrafast regime, the kinetic swelling
      curves exhibit a remarkable long-term behavior scaling as the logarithm of time,
      showing that the polymer membrane can continuously accommodate additional water
      molecules upon hydration stress. The present nanoscale kinetics results provide
      insights into the vapor-versus-liquid sorption mechanisms, the nanostructure of
      Nafion, and the role of polymer reorganization modes, highlighting that the
      membrane can never reach a steady state. 

PMID- 25971733
TI  - Traumatic experiences and re-victimization of female inmates undergoing treatment
      for substance abuse.
AB  - BACKGROUND: In the past decade, several studies have focused on the treatment
      needs of female inmates with substance abuse problems. An important finding has
      been that these women are more likely to report histories of sexual, physical,
      and emotional abuse-at rates varying from 77% to 90%. The trauma resulting from
      this kind of abuse is a key contributing factor in behavioral problems in
      adolescence and subsequent delinquency, substance abuse, and criminality in
      adulthood. METHODS: This was a retrospective clinical study. A convenience sample
      of 112 women who entered the program's treatment groups consecutively for one
      year form part of the study. Information on traumatic events was obtained using
      some questions from the Initial Trauma Review. It explores whether the
      participant experienced physical abuse, sexual abuse, disasters, automobile
      accidents, or witnessed violence under the age of 18. It also examines
      experiences as an adult, including sexual and physical abuse, attacks by others
      who are not intimate partners, and abuse by authorities. RESULTS: Revictimization
      in sexual abuse was found in 78.1% of participants. Significant differences were
      identified between women who had experienced a traumatic sexual event from a
      person five years their senior before the age of 18 and then suffered from sexual
      violence as an adult, and women who had never undergone either of these events
      (x(2) = 11.3, df 112/1, p = <.001). In physical abuse, the figure was 82.17%.
      Differences were observed between women who were revictimized through physical
      abuse before and after the age of 18 (x(2) = 5.91, df 112/1, p = <.01), and those
      who had not experienced any kind of revictimization. Significant differences were
      found between women who had suffered a traumatic sexual event as a child and
      subsequently physical violence from their parents, and women who had not
      undergone either of these events (x(2) = 3.48, df 112/1, p = <.05). CONCLUSIONS:
      Investment in treatment in these areas during the prison sentence and after
      release may contribute to preventing these women from become repeat offenders.
      Creating sources of work and halfway houses that continue the program to prevent
      relapses into substance use can help defend the human rights of this group of
      women and achieve social justice.

PMID- 25971735
TI  - Impacts from above-ground activities in the eagle ford shale play on landscapes
      and hydrologic flows, La Salle County, Texas.
AB  - We assess the spatial and geomorphic fragmentation from the recent Eagle Ford
      Shale play in La Salle County, Texas, USA. Wells and pipelines were overlaid onto
      base maps of land cover, soil properties, vegetation assemblages, and hydrologic
      units. Changes to continuity of different ecoregions and supporting landscapes
      were assessed using the Landscape Fragmentation Tool (a third-party ArcGIS
      extension) as quantified by land area and continuity of core landscape areas
      (i.e., those degraded by "edge effects"). Results show decreases in core areas
      (8.7%; ~33,290 ha) and increases in landscape patches (0.2%; ~640 ha), edges
      (1.8%; ~6940 ha), and perforated areas (4.2%; ~16230 ha). Pipeline construction
      dominates landscape disturbance, followed by drilling and injection pads (85, 15,
      and 0.03% of disturbed area, respectively). An increased potential for soil loss
      is indicated, with 51% (~5790 ha) of all disturbance regimes occurring on soils
      with low water-transmission rates (depth to impermeable layer less than 50 cm)
      and a high surface runoff potential (hydrologic soil group D). Additionally, 88%
      (~10,020 ha) of all disturbances occurred on soils with a wind erodibility index
      of approximately 19 kt/km(2)/year (0.19 kt/ha/year) or higher, resulting in an
      estimated potential of 2 million tons of soil loss per year. Results demonstrate
      that infrastructure placement is occurring on soils susceptible to erosion while
      reducing and splitting core areas potentially vital to ecosystem services.

PMID- 25971736
TI  - Community Resource Uses and Ethiopian Wolf Conservation in Mount Abune Yosef.
AB  - People who perceive economic benefits and enjoy unrestricted access to natural
      resources tend to support ecosystem conservation efforts. Our study explores
      whether this remains true in remnant patches of Afroalpine ecosystem in North
      Ethiopia, where communal land provides valuable natural resources for the local
      communities and also sustain small populations of the endangered Ethiopian wolf
      (Canis simensis). Questionnaires were designed to assess ecological and socio
      economic characteristics of the livelihoods of the Amhara people living in Mount
      Abune Yosef and their attitudes toward Afroalpine and Ethiopian wolf
      conservation. Of the 120 households interviewed, selected randomly from across
      eight villages, 80 % benefited from natural resources by grazing their livestock
      and harvesting firewood and grasses. The majority (90 %) also suffered from
      livestock predation by Ethiopian wolves and common jackals (Canis aureus) and
      crop raiding by geladas (Theropithecus gelada), birds, and rodents, yet more than
      half reported a positive attitudes toward Ethiopian wolves (66 %). People with
      positive attitudes tended to live close to the communal land, to own more
      livestock, and to be unaffected by conflict. Many also recognized the need to
      protect the Afroalpine habitats of Abune Yosef (71 %), and this attitude
      predominated among the literate, households that owned land, had smaller herds
      and were further away. We discussed how people's attitudes were modulated by
      human-wildlife conflicts and by the benefits derived from the access to natural
      resources in communal land, and the implications for the conservation of
      Afroalpine ecosystem and the flagship Ethiopian wolf.

PMID- 25971737
TI  - Stabilization of Stormwater Biofilters: Impacts of Wetting and Drying Phases and
      the Addition of Organic Matter to Filter Media.
AB  - Ripening period refers to a phase of stabilization in sand filters in water
      treatment systems that follow a new installation or cleaning of the filter.
      Intermittent wetting and drying, a unique property of stormwater biofilters,
      would similarly be subjected to a phase of stabilization. Suspended solids are an
      important parameter that is often used to monitor the stabilization of sand
      filters in water treatment systems. Stormwater biofilters, however, contain
      organic material that is added to the filter layer to enhance nitrate removal,
      the dynamics of which is seldom analyzed in stabilization of stormwater
      biofilters. Therefore, in this study of stormwater biofiltration in addition to
      suspended solids (turbidity), organic matter (TOC, DOC, TN, and TKN) was also
      monitored as a parameter for stabilization of the stormwater biofilter. One
      Perspex bioretention column (94 mm internal diameter) was fabricated with filter
      layer that contained 8 % organic material and fed with tapwater with different
      antecedent dry days (0-40 day) at 100 mL/min. Samples were collected from the
      outflow at different time intervals between 2 and 150 min and were tested for
      total organic carbon, dissolved organic carbon, total nitrogen, total Kjeldhal
      nitrogen, and turbidity. The column was observed to experience two phases of
      stabilization, one at the beginning of each event that lasted for 30 min, while
      the other phase was observed across subsequent events that are related to the age
      of filter.

PMID- 25971738
TI  - Use of the NatureServe Climate Change Vulnerability Index as an Assessment Tool
      for Reptiles and Amphibians: Lessons Learned.
AB  - Climate change threatens biodiversity globally, yet it can be challenging to
      predict which species may be most vulnerable. Given the scope of the problem, it
      is imperative to rapidly assess vulnerability and identify actions to decrease
      risk. Although a variety of tools have been developed to assess climate change
      vulnerability, few have been evaluated with regard to their suitability for
      certain taxonomic groups. Due to their ectothermic physiology, low vagility, and
      strong association with temporary wetlands, reptiles and amphibians may be
      particularly vulnerable relative to other groups. Here, we evaluate use of the
      NatureServe Climate Change Vulnerability Index (CCVI) to assess a large suite of
      herpetofauna from the Sand Hills Ecoregion of the southeastern United States.
      Although data were frequently lacking for certain variables (e.g., phenological
      response to climate change, genetic variation), sufficient data were available to
      evaluate all 117 species. Sensitivity analyses indicated that results were highly
      dependent on size of assessment area and climate scenario selection. In addition,
      several ecological traits common in, but relatively unique to, herpetofauna are
      likely to contribute to their vulnerability and need special consideration during
      the scoring process. Despite some limitations, the NatureServe CCVI was a useful
      tool for screening large numbers of reptile and amphibian species. We provide
      general recommendations as to how the CCVI tool's application to herpetofauna can
      be improved through more specific guidance to the user regarding how to
      incorporate unique physiological and behavioral traits into scoring existing
      sensitivity factors and through modification to the assessment tool itself. 

PMID- 25971739
TI  - Resting energy expenditure in OSAS: the impact of a single CPAP application.
AB  - PURPOSE: Data on the impact of obstructive sleep apnea syndrome (OSAS) and its
      treatment on resting energy expenditure (REE) are currently few and conflicting.
      The purpose of the present study was to investigate the impact of OSAS on REE, as
      measured before and after sleep, and the changes in REE after a single continuous
      positive airway pressure (CPAP) application, for the first time in literature.
      METHODS: This is a nested case-control study. From the initial study population,
      two groups were formed, based on the results of nocturnal polysomnography: a
      group of male OSAS patients and a group of male, age-matched non-OSAS controls.
      REE was measured in both groups before and after sleep by indirect calorimetry,
      while patients repeated REE measurements before and after a single nasal CPAP
      application. RESULTS: Ninety-two male OSAS patients (45.3 +/- 12.8 years old) and
      19 male non-OSAS controls (50.8 +/- 11.7 years old) were studied. REE/lean body
      mass (LBM) was higher among patients compared to controls both pre- (29.6 +/- 12
      vs 22.9 +/- 7.9 kcal/kg; p = 0.022, correspondingly) and post-sleep (26.4 +/- 9.6
      vs 21.6 +/- 9 kcal/kg; p = 0.047 correspondingly). REE/LBM decreased
      significantly after sleep in OSAS patients (p = 0.002), but not in controls; this
      difference was most evident among patients with more severe disease and higher
      desaturation. A single nasal CPAP application diminished the pre-post REE/LBM
      difference (30.3 +/- 8.2 vs 28.3 +/- 10.3 kcal/kg; p = 0.265), but only among
      responders. CONCLUSIONS: In OSAS patients, REE values are high and vary
      significantly before and after sleep. A single nasal CPAP application diminishes
      this difference among responders, possibly through reversal of nocturnal
      desaturation.

PMID- 25971740
TI  - CAPRI: efficient inference of cancer progression models from cross-sectional
      data.
AB  - We devise a novel inference algorithm to effectively solve the cancer progression
      model reconstruction problem. Our empirical analysis of the accuracy and
      convergence rate of our algorithm, CAncer PRogression Inference (CAPRI), shows
      that it outperforms the state-of-the-art algorithms addressing similar problems.
      MOTIVATION: Several cancer-related genomic data have become available (e.g. The
      Cancer Genome Atlas, TCGA) typically involving hundreds of patients. At present,
      most of these data are aggregated in a cross-sectional fashion providing all
      measurements at the time of diagnosis. Our goal is to infer cancer 'progression'
      models from such data. These models are represented as directed acyclic graphs
      (DAGs) of collections of 'selectivity' relations, where a mutation in a gene A
      'selects' for a later mutation in a gene B. Gaining insight into the structure of
      such progressions has the potential to improve both the stratification of
      patients and personalized therapy choices. RESULTS: The CAPRI algorithm relies on
      a scoring method based on a probabilistic theory developed by Suppes, coupled
      with bootstrap and maximum likelihood inference. The resulting algorithm is
      efficient, achieves high accuracy and has good complexity, also, in terms of
      convergence properties. CAPRI performs especially well in the presence of noise
      in the data, and with limited sample sizes. Moreover CAPRI, in contrast to other
      approaches, robustly reconstructs different types of confluent trajectories
      despite irregularities in the data. We also report on an ongoing investigation
      using CAPRI to study atypical Chronic Myeloid Leukemia, in which we uncovered non
      trivial selectivity relations and exclusivity patterns among key genomic events.
      AVAILABILITY AND IMPLEMENTATION: CAPRI is part of the TRanslational ONCOlogy R
      package and is freely available on the web at:
      http://bimib.disco.unimib.it/index.php/Tronco CONTACT:
      daniele.ramazzotti@disco.unimib.it SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 25971741
TI  - Fast parametric time warping of peak lists.
AB  - Alignment of peaks across samples is a difficult but unavoidable step in the data
      analysis for all analytical techniques containing a separation step like
      chromatography. Important application examples are the fields of metabolomics and
      proteomics. Parametric time warping (PTW) has already shown to be very useful in
      these fields because of the highly restricted form of the warping functions,
      avoiding overfitting. Here, we describe a new formulation of PTW, working on peak
      picked features rather than on complete profiles. Not only does this allow for a
      much more smooth integration in existing pipelines, it also speeds up the
      (already among the fastest) algorithm by orders of magnitude. Using two publicly
      available datasets we show the potential of the new approach. The first set is a
      LC-DAD dataset of grape samples, and the second an LC-MS dataset of apple
      extracts. AVAILABILITY AND IMPLEMENTATION: Parametric time warping of peak lists
      is implemented in the ptw package, version 1.9.1 and onwards, available from
      Github (https://github.com/rwehrens/ptw) and CRAN (http://cran.r-project.org).
      The package also contains a vignette, providing more theoretical details and
      scripts to reproduce the results below. CONTACT: ron.wehrens@wur.nl.

PMID- 25971742
TI  - GEO2Enrichr: browser extension and server app to extract gene sets from GEO and
      analyze them for biological functions.
AB  - MOTIVATION: Identification of differentially expressed genes is an important step
      in extracting knowledge from gene expression profiling studies. The raw
      expression data from microarray and other high-throughput technologies is
      deposited into the Gene Expression Omnibus (GEO) and served as Simple Omnibus
      Format in Text (SOFT) files. However, to extract and analyze differentially
      expressed genes from GEO requires significant computational skills. RESULTS: Here
      we introduce GEO2Enrichr, a browser extension for extracting differentially
      expressed gene sets from GEO and analyzing those sets with Enrichr, an
      independent gene set enrichment analysis tool containing over 70 000 annotated
      gene sets organized into 75 gene-set libraries. GEO2Enrichr adds JavaScript code
      to GEO web-pages; this code scrapes user selected accession numbers and metadata,
      and then, with one click, users can submit this information to a web-server
      application that downloads the SOFT files, parses, cleans and normalizes the
      data, identifies the differentially expressed genes, and then pipes the resulting
      gene lists to Enrichr for downstream functional analysis. GEO2Enrichr opens a new
      avenue for adding functionality to major bioinformatics resources such GEO by
      integrating tools and resources without the need for a plug-in architecture.
      Importantly, GEO2Enrichr helps researchers to quickly explore hypotheses with
      little technical overhead, lowering the barrier of entry for biologists by
      automating data processing steps needed for knowledge extraction from the major
      repository GEO. AVAILABILITY AND IMPLEMENTATION: GEO2Enrichr is an open source
      tool, freely available for installation as browser extensions at the Chrome Web
      Store and FireFox Add-ons. Documentation and a browser independent web
      application can be found at http://amp.pharm.mssm.edu/g2e/. CONTACT:
      avi.maayan@mssm.edu.

PMID- 25971744
TI  - Quality evaluation and pattern recognition analyses of bioactive marker compounds
      from Farfarae Flos using HPLC/PDA.
AB  - The flower bud of Tussilago farfara L., called Farfarae Flos, has traditionally
      been used in Oriental medicine for the treatment of bronchitis and asthma. To
      establish a standard for quality control as well as the reliable identification
      of Farfarae Flos, the contents of five standards, rutin (1), isoquercetin (2),
      3,5-dicaffeoylquinic acid (3), tussilagone (4), and tussilagonone (5), were
      determined by quantitative high-performance liquid chromatography
      (HPLC)/photodiode array (PDA) analysis. The five standards were separated on a
      YoungJinBioChrom Aegispak C18-L (250-mm*4.6-mm, 5-um) column by gradient elution
      using 0.03% trifluoroacetic acid in water (A), with acetonitrile (B) as the
      mobile phase. The flow rate was 1.0 mL/min, and the UV detector wavelength was
      set at 220 nm. The method was successfully used in the analysis of Farfarae Flos
      from different geographic origins with relatively simple conditions and
      procedures, and the results demonstrated satisfactory linearity, recovery,
      precision, accuracy, stability, and robustness. The HPLC analytical method for
      pattern recognition analysis was validated by repeated analysis of 62 Farfarae
      Flos samples. This result indicated that the established HPLC/PDA method is
      suitable for quantitation and pattern recognition analyses for the quality
      evaluation of Farfarae Flos. 

PMID- 25971743
TI  - GLASS: a comprehensive database for experimentally validated GPCR-ligand
      associations.
AB  - MOTIVATION: G protein-coupled receptors (GPCRs) are probably the most attractive
      drug target membrane proteins, which constitute nearly half of drug targets in
      the contemporary drug discovery industry. While the majority of drug discovery
      studies employ existing GPCR and ligand interactions to identify new compounds,
      there remains a shortage of specific databases with precisely annotated GPCR
      ligand associations. RESULTS: We have developed a new database, GLASS, which aims
      to provide a comprehensive, manually curated resource for experimentally
      validated GPCR-ligand associations. A new text-mining algorithm was proposed to
      collect GPCR-ligand interactions from the biomedical literature, which is then
      crosschecked with five primary pharmacological datasets, to enhance the coverage
      and accuracy of GPCR-ligand association data identifications. A special
      architecture has been designed to allow users for making homologous ligand search
      with flexible bioactivity parameters. The current database contains ~500 000
      unique entries, of which the vast majority stems from ligand associations with
      rhodopsin- and secretin-like receptors. The GLASS database should find its most
      useful application in various in silico GPCR screening and functional annotation
      studies. AVAILABILITY AND IMPLEMENTATION: The website of GLASS database is freely
      available at http://zhanglab.ccmb.med.umich.edu/GLASS/. CONTACT: zhng@umich.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25971745
TI  - Our unique microbial identity.
AB  - A recent article examines the extent of individual variation in microbial
      identities and how this might determine disease susceptibility, therapeutic
      responses and recovery from clinical interventions.

PMID- 25971747
TI  - Antenatal maternal low protein diet: ACE-2 in the mouse lung and sexually
      dimorphic programming of hypertension.
AB  - Elevated blood pressure is an important global health problem, and in-utero under
      nutrition may be an important factor in the pathogenesis of hypertension. In the
      present study, we tested the hypothesis that antenatal maternal low protein diet
      (MLPD) leads to sexually dimorphic developmental programming of the components of
      the pulmonary renin-angiotensin system. This may be important in the antenatal
      MLPD-associated development of hypertension. In pregnant mice, we administered
      normal (control) and isocaloric 50% protein restricted diet, commencing one week
      before mating and continuing until delivery of the pups. From the 18th to 24th
      week postnatal, we measured blood pressure in the offspring by use of a non
      invasive tail-cuff method. In the same mice, we examined the mRNA and protein
      expression of the key components of the pulmonary renin-angiotensin system. Also,
      we examined microRNA complementary to angiotensin converting enzymes (ACE) 2 in
      the offspring lungs. Our results demonstrate that as a consequence of antenatal
      MLPD: 1) pup birthweight was significantly reduced in both sexes. 2) female
      offspring developed hypertension, but males did not. 3) In female offspring, ACE
      2 protein expression was significantly reduced without any change in the mRNA
      levels. 4) miRNA 429, which has a binding site on ACE-2 - 3' UTR was
      significantly upregulated in the female antenatal MLPD offspring. 5) In males,
      ACE-2 mRNA and protein expression were unaltered. We conclude that in the mouse,
      antenatal MLPD-induced reduction of ACE-2 in the female offspring lung may be an
      important mechanisms in sexually dimorphic programming of hypertension.

PMID- 25971746
TI  - NF-kappaB induces miR-148a to sustain TGF-beta/Smad signaling activation in
      glioblastoma.
AB  - BACKGROUND: Inflammatory cytokines and transforming growth factor-beta (TGF-beta)
      are mutually inhibitory. However, hyperactivation of nuclear factor-kappaB (NF
      kappaB) and TGF-beta signaling both emerge in glioblastoma. Here, we report
      microRNA-148a (miR-148a) overexpression in glioblastoma and that miR-148a
      directly suppressed Quaking (QKI), a negative regulator of TGF-beta signaling.
      METHODS: We determined NF-kappaB and TGF-beta/Smad signaling activity using pNF
      kappaB-luc, pSMAD-luc, and control plasmids. The association between an RNA
      induced silencing complex and QKI, mitogen-inducible gene 6 (MIG6), S-phase
      kinase-associated protein 1 (SKP1), and glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) mRNA was tested with microribonucleoprotein immunoprecipitation and real
      time PCR. Xenograft tumors were established in the brains of nude mice. RESULTS:
      QKI suppression induced an aggressive phenotype of glioblastoma cells both in
      vitro and in vivo. Interestingly, we found that NF-kappaB induced miR-148a
      expression, leading to enhanced-strength and prolonged-duration TGF-beta/Smad
      signaling. Notably, these findings were consistent with the significant
      correlation between miR-148a levels with NF-kappaB hyperactivation and activated
      TGF-beta/Smad signaling in a cohort of human glioblastoma specimens. CONCLUSIONS:
      These findings uncover a plausible mechanism for NF-kappaB-sustained TGF
      beta/Smad activation via miR-148a in glioblastoma, and may suggest a new target
      for clinical intervention in human cancer.

PMID- 25971749
TI  - Improvement science and the future of family medicine.

PMID- 25971748
TI  - Primary care quality between Traditional Tibetan Medicine and Western Medicine
      Hospitals: a pilot assessment in Tibet.
AB  - INTRODUCTION: This paper assesses both patients' perspectives on the differences
      in primary care quality between traditional Tibetan medicine (TTM) hospitals and
      western medicine (WM) hospitals and the efficacy of the government's investment
      in these two Prefecture-level primary care structures in Tibet. METHOD: A
      validated Tibetan version of the Primary Care Assessment Tool (PCAT-T) was used
      to collect data on 692 patients aged over 18 years old, who reported the sampling
      site was their regular source of health care. T-tests were performed to compare
      the separate and total primary care attributes between WM hospitals and TTM
      hospitals. Multiple linear regression analysis was conducted to examine the
      association of the health care setting with primary care attributes while
      controlling for socio-demographic, health service use and health status
      characteristics. RESULTS: Compared to WM hospitals, the results showed that TTM
      hospitals had patients who were older (15.8 % versus 8.4 % over 60 years); with
      lower education levels (66.0 % versus 35.8 % with below junior high school ) and
      income levels (46.9 % versus 26.5 % with annual household income below
      30,000RMB); more likely to be married (79.2 % versus 60.5 %); made less frequent
      health care visits; and had higher self-rated health status. Overall, patients
      assessed the primary care performance in TTM hospitals significantly higher
      (80.0) than WM hospitals (74.63). There were no differences in health care
      assessment by patient gender, age, income, education, marital status and
      occupation. CONCLUSIONS: TTM patients reported better primary care experiences
      than patients using WM hospitals, which validated the government's investment in
      traditional Tibetan medicine.

PMID- 25971751
TI  - Challenge of same-day access in primary care.

PMID- 25971752
TI  - Bringing Canada together: Effective organizational structure for
      multijurisdictional health services research projects.

PMID- 25971755
TI  - EMRs are here to stay, but ...

PMID- 25971756
TI  - Horses and buggies have some advantages over cars, but no one is turning back.

PMID- 25971757
TI  - Prescribing income.

PMID- 25971758
TI  - Approach to autism spectrum disorder: Using the new DSM-V diagnostic criteria and
      the CanMEDS-FM framework.
AB  - OBJECTIVE: To review the diagnostic criteria for autism spectrum disorder (ASD)
      from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition
      (DSM-V), and to develop an approach to managing ASD using the CanMEDS- Family
      Medicine (CanMEDS-FM) framework. SOURCES OF INFORMATION: The DSM-V from the
      American Psychiatric Association, published in May 2013, provides new diagnostic
      criteria for ASD. The College of Family Physicians of Canada's CanMEDS-FM
      framework provides a blueprint that can guide the complex management of ASD. We
      used data from the Centers for Disease Control and Prevention to determine the
      prevalence of ASD, and we used the comprehensive systematic review and meta
      analysis completed by the UK National Institute for Health and Care Excellence
      for their guidelines on ASD to assess the evidence for more than 100
      interventions. MAIN MESSAGE: The prevalence of ASD was 1 in 88 in 2008 in the
      United States according to data from the Centers for Disease Control and
      Prevention. The ASD classification in the fourth edition of the DSM included
      autism, Asperger syndrome, pervasive developmental disorder, and childhood
      disintegrative disorder. The new DSM-V revision incorporates all these disorders
      into one ASD umbrella term with different severity levels. The management of ASD
      is complex and requires a multidisciplinary team effort and continuity of care.
      The CanMEDS-FM roles provide a framework for management. CONCLUSION: Family
      physicians are the key leaders of the multidisciplinary care team for ASD, and
      the CanMEDS-FM framework provides a comprehensive guide to help manage a child
      with ASD and to help the child's family.

PMID- 25971760
TI  - Bisphosphonates: forever or 5 years and stop?

PMID- 25971759
TI  - Intranasal sumatriptan for migraine in children.
AB  - QUESTION: I am seeing more and more children and adolescents with headaches that
      can be defined as migraine headache. I have read about intranasal sumatriptan as
      an abortive therapy. Is this an effective treatment? ANSWER: Acute migraine
      headache among children and adolescents is common and treatment is challenging.
      Intranasal sumatriptan is a safe and mostly effective option for children and
      adolescents. Currently the recommended dose is 20 mg for children who weigh more
      than 40 kg and 10 mg for children who weigh between 20 and 39 kg. Larger trials
      should be conducted to overcome the limitations of small sample sizes, potential
      low plasma concentration, and placebo effects witnessed in studies to date.

PMID- 25971761
TI  - Breaking down barriers to initiating insulin: Insulin prescription pad.

PMID- 25971762
TI  - Ecology of health care in Canada.
AB  - OBJECTIVE: To provide a population-based, Canada-wide picture of health care
      needs and health care use, and present it in a highly accessible manner, allowing
      provincial comparisons and comparisons with other international jurisdictions.
      DESIGN: A comparison of the rates of health care use among jurisdictions, using
      Canadian-population survey data and health administrative data. SETTING:
      Provincial jurisdictions across Canada. MAIN OUTCOME MEASURES: Canadian and
      provincial rates of ill health (presence of chronic conditions) and health care
      use (contacts with family physicians, contacts with other specialist physicians,
      contacts with nurses, and hospitalizations) as monthly rates per 1000 population
      standardized by age and sex. RESULTS: The monthly rate per 1000 population of
      having at least 1 chronic condition ranged from 524 in Quebec to 638 in Nova
      Scotia; contacts with family physicians ranged from 158 in Quebec to 295 in
      British Columbia; contacts with other physician specialists ranged from 53 in
      Saskatchewan to 79 in Ontario; and contacts with nurses ranged from 23 in British
      Columbia to 41 in Quebec. Hospital stays ranged from 8 to 11 per 1000 people, and
      rates were similar among the provinces. CONCLUSION: Recognizing the differences
      among jurisdictions is critical to informing health care policy across the
      country. Differences persisted when rates were standardized for different age and
      sex compositions in the provinces. This article provides a straightforward
      methodology using publicly available data that can be employed in each province
      to examine, in the future, the evolution over time of health care use by
      provincial jurisdictions.

PMID- 25971763
TI  - Since I've been a patient.

PMID- 25971764
TI  - Dr Vincent Ip MD MRCP.

PMID- 25971765
TI  - Protecting children.

PMID- 25971768
TI  - Tribute to Lynn Dunikowski and the Canadian Library of Family Medicine.

PMID- 25971769
TI  - Discovery of bicyclic pyrazoles as class III histone deacetylase SIRT1 and SIRT2
      inhibitors.
AB  - A series of bicyclic pyrazole carboxamides was synthesized and tested for
      inhibitory activity against the class III deacetylase sirtuin enzymes. Moderate
      to low micromolar inhibitory activities were obtained against SIRT1 and SIRT2.
      These bicyclic pyrazole compounds represent a new class of sirtuin inhibitors
      with a preference for SIRT1 over SIRT2. 

PMID- 25971770
TI  - Progress in discovery of small-molecule modulators of protein-protein
      interactions via fragment screening.
AB  - Protein-protein interactions (PPIs) present a formidable challenge to medicinal
      chemistry. The extended and open nature of many binding sites at protein
      interfaces has made it difficult to find useful chemical matter by traditional
      screening methods using standard screening libraries. This Digest focuses on the
      progress that has been made in discovering small-molecule modulators for a
      diverse selection of PPI targets using fragment screening and highlights the
      utility of this strategy in this context. 

PMID- 25971771
TI  - N-acetyl cysteine and mushroom Agaricus sylvaticus supplementation decreased
      parasitaemia and pulmonary oxidative stress in a mice model of malaria.
AB  - BACKGROUND: Malaria infection can cause high oxidative stress, which could lead
      to the development of severe forms of malaria, such as pulmonary malaria. In
      recent years, the role of reactive oxygen species in the pathogenesis of the
      disease has been discussed, as well as the potential benefit of antioxidants
      supplementation. The aim of this study was to investigate the effects of N-acetyl
      cysteine (NAC) or mushroom Agaricus sylvaticus supplementation on the pulmonary
      oxidative changes in an experimental model of malaria caused by Plasmodium
      berghei strain ANKA. METHODS: Swiss male mice were infected with P. berghei and
      treated with NAC or AS. Samples of lung tissue and whole blood were collected
      after one, three, five, seven or ten days of infection for the assessment of
      thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant
      capacity (TEAC), nitrites and nitrates (NN) and to assess the degree of
      parasitaemia. RESULTS: Although parasitaemia increased progressively with the
      evolution of the disease in all infected groups, there was a significant decrease
      from the seventh to the tenth day of infection in both antioxidant-supplemented
      groups. Results showed significant higher levels of TEAC in both supplemented
      groups, the highest occurring in the group supplemented with A. sylvaticus. In
      parallel, TBARS showed similar levels among all groups, while levels of NN were
      higher in animals supplemented with NAC in relation to the positive control
      groups and A. sylvaticus, whose levels were similar to the negative control
      group. CONCLUSION: Oxidative stress arising from plasmodial infection was
      attenuated by supplementation of both antioxidants, but A. sylvaticus proved to
      be more effective and has the potential to become an important tool in the
      adjuvant therapy of malaria.

PMID- 25971772
TI  - Voxel modeling of rabbits for use in radiological dose rate calculations.
AB  - Radiation dose to biota is generally calculated using Monte Carlo simulations of
      whole body ellipsoids with homogeneously distributed radioactivity throughout.
      More complex anatomical phantoms, termed voxel phantoms, have been developed to
      test the validity of these simplistic geometric models. In most voxel models
      created to date, human tissue composition and density values have been used in
      lieu of biologically accurate values for non-human biota. This has raised
      questions regarding variable tissue composition and density effects on the
      fraction of radioactive emission energy absorbed within tissues (e.g. the
      absorbed fraction - AF), along with implications for age-dependent dose rates as
      organisms mature. The results of this study on rabbits indicates that the
      variation in composition between two mammalian tissue types (e.g. human vs rabbit
      bones) made little difference in self-AF (SAF) values (within 5% over most energy
      ranges). However, variable tissue density (e.g. bone vs liver) can significantly
      impact SAF values. An examination of differences across life-stages revealed
      increasing SAF with testis and ovary size of over an order of magnitude for
      photons and several factors for electrons, indicating the potential for
      increasing dose rates to these sensitive organs as animals mature. AFs for
      electron energies of 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, 2.0, and 4.0 MeV and
      photon energies of 0.01, 0.015, 0.02, 0.03, 0.05, 0.1, 0.2, 0.5, 1.0, 1.5, 2.0,
      and 4.0 MeV are provided for eleven rabbit tissues. The data presented in this
      study can be used to calculate accurate organ dose rates for rabbits and other
      small rodents; to aide in extending dose results among different mammal species;
      and to validate the use of ellipsoidal models for regulatory purposes. 

PMID- 25971774
TI  - Does a local financial incentive scheme reduce inequalities in the delivery of
      clinical care in a socially deprived community? A longitudinal data analysis.
AB  - BACKGROUND: Socioeconomic deprivation is associated with inequalities in health
      care and outcomes. Despite concerns that the Quality and Outcomes Framework pay
      for-performance scheme in the UK would exacerbate inequalities in primary care
      delivery, gaps closed over time. Local schemes were promoted as a means of
      improving clinical engagement by addressing local health priorities. We evaluated
      equity in achievement of target indicators and practice income for one local
      scheme. METHODS: We undertook a longitudinal survey over four years of routinely
      recorded clinical data for all 83 primary care practices. Sixteen indicators were
      developed that covered five local clinical and public health priorities: weight
      management; alcohol consumption; learning disabilities; osteoporosis; and
      chlamydia screening. Clinical indicators were logit transformed from a percentage
      achievement scale and modelled allowing for clustering of repeated measures
      within practices. This enabled our study of target achievements over time with
      respect to deprivation. Practice income was also explored. RESULTS: Higher
      practice deprivation was associated with poorer performance for five indicators:
      alcohol use registration (OR 0.97; 95 % confidence interval 0.96,0.99); recorded
      chlamydia test result (OR 0.97; 0.94,0.99); osteoporosis registration (OR 0.98;
      0.97,0.99); registration of repeat prednisolone prescription (OR 0.98;
      0.96,0.99); and prednisolone registration with record of dual energy X-ray
      absorptiometry (DEXA) scan/referral (OR 0.92; 0.86,0.97); practices in deprived
      areas performed better for one indicator (registration of osteoporotic fragility
      fracture (OR 1.26; 1.04,1.51). The deprivation-achievement gap widened for one
      indicator (registered females aged 65-74 with a fracture referred for a DEXA
      scan; OR 0.97; 0.95,0.99). Two other indicators indicated a similar trend over
      two years before being withdrawn (registration of fragility fracture and over-75
      s with a fragility fracture assessed and treated for osteoporosis risk). For one
      indicator the deprivation-achievement gap reduced over time (repeat prednisolone
      prescription (OR 1.01; 1.01,1.01). Larger practices and those serving more
      affluent areas earned more income per patient than smaller practices and those
      serving more deprived areas (t = -3.99; p =0.0001). CONCLUSIONS: Any gaps in
      achievement between practices were modest but mostly sustained or widened over
      the duration of the scheme. Given that financial rewards may not reflect the
      amount of work undertaken by practices serving more deprived patients, future pay
      for-performance schemes also need to address fairness of rewards in relation to
      workload.

PMID- 25971775
TI  - Not4-dependent translational repression is important for cellular protein
      homeostasis in yeast.
AB  - Translation of aberrant or problematic mRNAs can cause ribosome stalling which
      leads to the production of truncated or defective proteins. Therefore, cells
      evolved cotranslational quality control mechanisms that eliminate these
      transcripts and target arrested nascent polypeptides for proteasomal degradation.
      Here we show that Not4, which is part of the multifunctional Ccr4-Not complex in
      yeast, associates with polysomes and contributes to the negative regulation of
      protein synthesis. Not4 is involved in translational repression of transcripts
      that cause transient ribosome stalling. The absence of Not4 affected global
      translational repression upon nutrient withdrawal, enhanced the expression of
      arrested nascent polypeptides and caused constitutive protein folding stress and
      aggregation. Similar defects were observed in cells with impaired mRNA decapping
      protein function and in cells lacking the mRNA decapping activator and
      translational repressor Dhh1. The results suggest a role for Not4 together with
      components of the decapping machinery in the regulation of protein expression on
      the mRNA level and emphasize the importance of translational repression for the
      maintenance of proteome integrity. 

PMID- 25971777
TI  - Simply the right time to turn on insulin.

PMID- 25971776
TI  - Poised for action: USP18 restrains microglial activation in the white matter.

PMID- 25971778
TI  - Modern abbreviated computer navigation of the femur reduces blood loss in total
      knee arthroplasty.
AB  - Computer assisted surgery (CAS) optimizes component position in total knee
      arthroplasty (TKA), yet effects specifically on blood loss are less known. This
      study purpose was to determine whether a modern abbreviated CAS protocol would
      reduce blood loss in TKA compared to conventional instrumentation. One hundred
      consecutive TKAs were retrospectively reviewed comparing abbreviated CAS versus
      conventional IM instrumentation. Blood loss was determined using drain output,
      change in hemoglobin, and calculated blood loss. The CAS group demonstrated less
      hourly drain output (P=0.02), hemoglobin change (P=0.001), and estimated blood
      loss (P=0.001) versus conventional instrumentation. With proven advantages of
      accurate component placement and improved functional outcome after TKA, CAS
      provides additional value by reducing blood loss in TKA. 

PMID- 25971779
TI  - Social and Behavioral Factors in Total Knee and Hip Arthroplasty.
AB  - Social and behavioral factors are important determinants of health outcomes in a
      number of medical conditions but their role in joint arthroplasty is poorly
      understood. In a cohort of 20,124 hip and knee arthroplasty procedures, smoking
      was associated with a significantly higher risk of surgical site infections
      (hazard ratio 1.7, 95% CI: 1.1-2.6), whereas alcohol use was associated with a
      lower risk of reoperations and revisions (hazard ratio 0.7, 95% CI: 0.5-0.8).
      There was no association between marital status and educational attainment with
      the risk of complications or reoperations in total hip and knee arthroplasty. 

PMID- 25971781
TI  - Comparing effectiveness of two client follow-up approaches in sustaining the use
      of Long Acting Reversible Contraceptives (LARC) among the underserved in rural
      Punjab, Pakistan: a study protocol and participants' profile.
AB  - BACKGROUND: Pakistan observes a very high i.e. 37 percent modern contraceptive
      method related discontinuation rates within 12 months of their initiation. And
      almost 10 percent of these episodes of discontinuation happened due to the side
      effects or health concerns experienced by the women. Most importantly, it was
      noted that more than 12,000 first-level care facilities are located in the rural
      areas, including rural health centers, basic health units, and family welfare
      centers, but more than 30% of these facilities are nonfunctional. This paper
      presents a study protocol and participants' profiling of a prospective cohort
      follow-up to compare the effectiveness of household based and telephonic
      approaches in sustaining the use of Long Acting Reversible Contraceptives (LARC)
      whilst to facilitate lowering method related discontinuation and increasing
      switching amongst the contraceptive users. METHODS: A 12-month multi-centre, non
      inferiority prospective user follow-up is employed using three different study
      categories: a) household based follow-up; b) telephonic follow-up; and c) passive
      or need-based follow-up along with the hypothetical assumption that the
      telephonic client follow-up is not inferior to the household based follow-up by
      continuation rate of LARC and the telephonic follow-up is less-costly than the
      household based client follow-up. This follow-up will be conducted in 22 health
      facilities - (16 rural and 6 urban based facilities) in district Chakwal. The
      first two study categories will receive scheduled but different follow-up from
      the field workers at 1, 3, 6, 9, and 12 month while the third one i.e. the
      'passive or need-based follow-up' will serve as a control group. Using sampling
      software PASS 11, it was estimated to have 414 clients in each study category and
      around 1366 clients will be recruited to account for 10% attrition rate.
      DISCUSSION: The study will help us to examine a more convenient method of
      effective follow-up for managing side effects, decreasing method discontinuation
      and increasing switching amongst users. The study information will also
      facilitate to develop a robust, effective and efficient mechanism for client
      follow-up to promote the continuation rates of LARC methods. The follow-up
      results and lessons learnt will be widely shared with stakeholders for their
      implementation and streamlining in health system.

PMID- 25971780
TI  - Reductions in behavioral deficits and neuropathology in the R6/2 mouse model of
      Huntington's disease following transplantation of bone-marrow-derived mesenchymal
      stem cells is dependent on passage number.
AB  - INTRODUCTION: Huntington's disease (HD) is an autosomal dominant disorder caused
      by an expanded CAG repeat (greater than 38) on the short arm of chromosome 4,
      resulting in loss and dysfunction of neurons in the neostriatum and cortex,
      leading to cognitive decline, motor dysfunction, and death, typically occurring
      15 to 20 years after the onset of motor symptoms. Although an effective treatment
      for HD has remained elusive, current studies using transplants of bone-marrow
      derived mesenchymal stem cells provides considerable promise. This study further
      investigates the efficacy of these transplants with a focus on comparing how
      passage number of these cells may affect subsequent efficacy following
      transplantation. METHODS: In this study, mesenchymal stem cells isolated from the
      bone-marrow of mice (BM MSCs), were labeled with Hoechst after low (3 to 8) or
      high (40 to 50) numbers of passages and then transplanted intrastriatally into 5
      week-old R6/2 mice, which carries the N-terminal fragment of the human HD gene
      (145 to 155 repeats) and rapidly develops symptoms analogous to the human form of
      the disease. RESULTS: It was observed that the transplanted cells survived and
      the R6/2 mice displayed significant behavioral and morphological sparing compared
      to untreated R6/2 mice, with R6/2 mice receiving high passage BM MSCs displaying
      fewer deficits than those receiving low-passage BM MSCs. These beneficial effects
      are likely due to trophic support, as an increase in brain derived neurotrophic
      factor mRNA expression was observed in the striatum following transplantation of
      BM MSCs. CONCLUSION: The results from this study demonstrate that BM MSCs hold
      significant therapeutic value for HD, and that the amount of time the cells are
      exposed to in vitro culture conditions can alter their efficacy.

PMID- 25971783
TI  - (2 + 2) Cycloaddition of Benzyne to Endohedral Metallofullerenes M3N@C80 (M = Sc,
      Y): A Rotating-Intermediate Mechanism.
AB  - The reaction mechanism and origin of regioselectivity of (2 + 2) cycloadditions
      of benzyne to endohedral metallofullerenes M3N@C80 (M = Sc, Y) were investigated
      with density functional calculations. The reaction was demonstrated to follow a
      diradical mechanism rather than a carbene mechanism, in which the formation of
      the diradical intermediate is the rate-determining step. Through rotation of
      benzyne moiety on the fullerene surface, the diradical intermediate on 566 site
      could isomerize to two new diradical intermediates which give rise to two
      distinct [5,6] and [6,6] benzoadducts, respectively. However, the diradical
      intermediate on 666 site only produces the [6,6] benzoadduct. The nature of the
      endohedral cluster not only influences the regioselectivity, but also determines
      the cycloadduct geometry. For Sc3N@C80, the [5,6] benzoadduct is preferred
      kinetically and thermodynamically, whereas in the case of Y3N@C80, both [5,6] and
      [6,6] benzoadducts are favorable. In contrast to closed-cage benzoadducts of
      Sc3N@C80, Y3N@C80 affords open-cage benzoadducts, making it the first example
      that the endohedral cluster could alter cycloadducts from the closed cage to open
      cage. With further analysis, it is revealed that the origin of regioselectivity
      results from the local strain energy of the fullerene cage. 

PMID- 25971782
TI  - Structural Characterization of Methylenedianiline Regioisomers by Ion Mobility
      Mass Spectrometry, Tandem Mass Spectrometry, and Computational Strategies. 2.
      Electrospray Spectra of 3-Ring and 4-Ring Isomers.
AB  - Building on results from our previous study of 2-ring methylenedianiline (MDA), a
      combined mass spectrometry approach utilizing ion mobility-mass spectrometry (IM
      MS) and tandem mass spectrometry (MS/MS) coupled with computational methods
      enables the structural characterization of purified 3-ring and 4-ring MDA
      regioisomers in this current study. The preferred site of protonation for the 3
      ring and 4-ring MDA was determined to be on the amino groups. Additionally, the
      location of the protonated amine along the MDA multimer was found to influence
      the gas phase stability of these molecules. Fragmentation mechanisms similar to
      the 2-ring MDA species were observed for both the 3-ring and 4-ring MDA. The
      structural characterization of 3-ring and 4-ring MDA isomers using modern MS
      techniques may aid polyurethane synthesis by the characterization of industrial
      grade MDA, multimeric MDA species, and methylene diphenyl diisocyanate (MDI)
      mixtures. 

PMID- 25971784
TI  - Smaller amygdala and medial prefrontal cortex predict escalating stimulant use.
AB  - Drug addiction is a chronic, relapsing brain disorder. The identification of
      biomarkers that render individuals vulnerable for the transition from occasional
      drug use to addiction is of key importance to develop early intervention
      strategies. The aim of the present study was to prospectively assess brain
      structural markers for escalating drug use in two independent samples of
      occasional amphetamine-type stimulant users. At baseline occasional users of
      amphetamine and 3,4-methylenedioxymethamphetamine (cumulative lifetime use <=10
      units) underwent structural brain imaging and were followed up at 12 months and
      24 months (Study 1, n = 38; Study 2, n = 28). Structural vulnerability markers
      for escalating amphetamine-type drug use were examined by comparing baseline grey
      matter volumes of participants who increased use with those who maintained or
      reduced use during the follow-up period. Participants in both samples who
      subsequently increased amphetamine-type drugs use displayed smaller medial
      prefrontal cortex volumes and, additionally, in the basolateral amygdala (Study
      1) and dorsal striatum (Study 2). In both samples the baseline volumes were
      significantly negatively correlated with stimulant use during the subsequent 12
      and 24 months. Additional multiple regression analyses on the pooled data sets
      revealed some evidence of a compound-specific association between the baseline
      volume of the left basolateral amygdala and the subsequent use of amphetamine.
      These findings indicate that smaller brain volumes in fronto-striato-limbic
      regions implicated in impulsivity and decision-making might render an individual
      vulnerable for the transition from occasional to escalating amphetamine-type
      stimulant use. 

PMID- 25971785
TI  - A Long Fragment Aligner called ALFALFA.
AB  - BACKGROUND: Rapid evolutions in sequencing technology force read mappers into
      flexible adaptation to longer reads, changing error models, memory barriers and
      novel applications. RESULTS: ALFALFA achieves a high performance in accurately
      mapping long single-end and paired-end reads to gigabase-scale reference genomes,
      while remaining competitive for mapping shorter reads. Its seed-and-extend
      workflow is underpinned by fast retrieval of super-maximal exact matches from an
      enhanced sparse suffix array, with flexible parameter tuning to balance
      performance, memory footprint and accuracy. CONCLUSIONS: ALFALFA is open source
      and available at http://alfalfa.ugent.be .

PMID- 25971786
TI  - Periodontitis associated with plasminogen deficiency: a case report.
AB  - BACKGROUND: Plasminogen deficiency is a rare autosomal recessive disease, which
      is associated with aggressive periodontitis and gingival enlargement. Previously
      described treatments of plasminogen deficiency associated periodontitis have
      shown limited success. This is the first case report indicating a successful
      therapy approach consisting of a non-surgical supra- and subgingival debridement
      in combination with an adjunctive systemic antibiotic therapy and a strict
      supportive periodontal regimen over an observation period of 4 years. CASE
      PRESENTATION: The intraoral examination of a 17-year-old Turkish female with
      severe plasminogen deficiency revealed generalized increased pocket probing
      depths ranging from 6 to 9 mm, bleeding on probing over 30%, generalized tooth
      mobility, and gingival hyperplasia. Alveolar bone loss ranged from 30% to 50%.
      Clinical attachment loss corresponded to pocket probing depths. Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Prevotella
      intermedia, Prevotella nigrescens and Eikenella corrodens have been detected by
      realtime polymerase chain reaction. Periodontal treatment consisted of full mouth
      disinfection and adjunctive systemic administration of amoxicillin (500 mg tid)
      and metronidazole (400 mg tid). A strict supportive periodontal therapy regimen
      every three month in terms of supra- and subgingival debridement was rendered.
      The reported therapy has significantly improved periodontal health and arrested
      disease progression. Intraoral examination at the end of the observation period
      3.5 years after non-surgical periodontal therapy showed generalized decreased
      pocket probing depths ranging from 1 to 6 mm, bleeding on probing lower 30%, and
      tooth mobility class I and II. Furthermore, microbiological analysis shows the
      absence of Porphyromonas gingivalis, Prevotella intermedia and Treponema
      denticola after therapy. CONCLUSION: Adjunctive antibiotic treatment may alter
      the oral microbiome and thus, the inflammatory response of periodontal disease
      associated to plasminogen deficiency and diminishes the risk of pseudomembrane
      formation and progressive attachment loss. This case report indicates that
      patients with plasminogen deficiency may benefit from non-surgical periodontal
      treatment in combination with an adjunctive antibiotic therapy and a strict
      supportive periodontal therapy regimen.

PMID- 25971788
TI  - Impact of rapid diagnostic tests for the diagnosis and treatment of malaria at a
      peripheral health facility in Western Uganda: an interrupted time series
      analysis.
AB  - BACKGROUND: The World Health Organization recommends that all suspected malaria
      cases receive a parasitological diagnosis prior to treatment with artemisinin
      based combination therapy. A recent meta-analysis of clinical trials evaluating
      RDTs for the management of patients with fever found substantial reductions in
      anti-malarial prescriptions when health workers adhered to treatment protocols
      based on test results. However few studies have reported on the impact of RDTs on
      health systems outside research settings. METHODS: The study comprised a
      retrospective interrupted time series analysis, comparing rates of malaria
      diagnosis, treatment, and resource utilization before and after introduction of
      RDTs at a peripheral health facility in rural Western Uganda. The use of malaria
      diagnostic tests was graphically depicted throughout the study period and fit
      regression models to identify correlates of three outcomes of interest: (1)
      length of stay (2) the proportion of patients referred to a higher-level health
      facility, and (3) administration of antibiotics. RESULTS: Over the course of the
      study period, 14,357 individuals underwent diagnostic testing for malaria with
      either a RDT (9,807) or microscopy (4,550). The proportion of patients with
      parasite-based diagnoses more than tripled to 34% after the introduction of RDTs.
      RDTs largely replaced microscopy as the diagnostic method of choice. Compared to
      patients admitted during the pre-RDT period, patients admitted to the health
      centre with malaria in the post-RDT period had significantly reduced odds of
      being referred to another health centre (AOR=0.49, P=0.038), receiving
      antibiotics (AOR=0.42, P<0.001), and a significantly shorter mean length of stay
      (beta=-0.32 days, 95%CI -0.52 to -0.13). CONCLUSIONS: This study is one of the
      few to demonstrate significant improvement in clinical outcomes and process
      measures following the introduction of RDTs for the diagnosis of malaria at a
      rural health facility in Uganda. The results show a reduction in referrals and
      shorter mean inpatient LOS even as antibiotics were prescribed less frequently.
      This change greatly increased laboratory throughput and the resultant proportion
      of patients receiving a parasite-based diagnosis.

PMID- 25971787
TI  - Ginsenoside Rg1 relieves tert-Butyl hydroperoxide-induced cell impairment in
      mouse microglial BV2 cells.
AB  - Microglial activation plays an important role in neurodegenerative diseases
      associated with oxidative stress. tert-Butyl hydroperoxide (t-BHP), an analog of
      hydroperoxide, mimics the oxidative damage to microglial cells. It has been
      reported that ginsenoside Rg1 (G-Rg1), an active ingredient of Panax ginseng, has
      anti-stress and anti-inflammatory properties. The present study aims to
      investigate the ability of G-Rg1 to decrease the t-BHP-mediated cell damage of
      BV2 microglial cells. We performed flow cytometry assays to facilitate the
      detection of reactive oxygen species as well as Western blotting analyses and
      immunofluorescence assays using specific antibodies, such as antibodies against
      phospho-mitogen-activated protein kinases (p-MAPKs), phospho-nuclear factor
      kappaB (p-NF-kappaB), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax),
      Caspase-3, autophagy marker light chain 3 (LC3), and Becline-1. We found that
      treatment with 50 MUM G-Rg1 protected microglial cells against oxidative damage
      induced by 10 MUM t-BHP.

PMID- 25971789
TI  - Gallstone ileus treated with non-surgical conservative methods: a case report.
AB  - INTRODUCTION: The preoperative diagnosis of gallstone ileus is challenging due to
      the variability of its presentation, often resulting in late diagnosis.
      Controversy remains regarding the management of gallstone ileus; surgery is the
      standard treatment, but also less invasive approaches have proven to be
      successful. We present an unusual case of gallstone ileus and its conservative
      treatment. CASE PRESENTATION: We describe the case of a 49-year-old Caucasian
      woman with a bowel sub-occlusion, treated conservatively. The imaging technique
      (plain abdominal X-ray and computed tomography scan) led to a diagnosis of
      gallstones ileus. A surgical intervention was not performed. Instead, she
      underwent extracorporeal shock-wave lithotripsy to fragment the stones,
      mechanical intestinal dilatation for ileocolic stenosis and endoscopic removal of
      the gallstone. The presence of an apricot shell contributed to the bowel
      occlusion and was removed. The intervention was successful and without
      complications. CONCLUSIONS: Given the variability of the gallstone ileus
      presentation, surgery could not be the only treatment for our patient. In our
      case report, we show that colonoscopy could be a non-invasive approach that
      allows for diagnosis and treatment at the same time. The available data do not
      show a higher rate of recurrent biliary disease in cases where this method has
      been used, therefore in select patients, a conservative treatment could be an
      effective solution.

PMID- 25971791
TI  - Perceived barriers to computerised quality documentation during anaesthesia: a
      survey of anaesthesia staff.
AB  - BACKGROUND: Underreporting of intraoperative events in anaesthesia is well-known
      and compromises quality documentation. The reasons for such omissions remain
      unclear. We conducted a questionnaire-based survey of anaesthesia staff to
      explore perceived barriers to reliable documentation during anaesthesia. METHODS:
      Participants anonymously completed a paper-based questionnaire. Predefined
      answers referred to potential barriers. Additional written comments were
      encouraged. Differences between physician and nurse anaesthetists were tested
      with t-tests and chi-square tests. RESULTS: Twenty-five physician and 30 nurse
      anaesthetists (81% of total staff) completed the survey. The reported problems
      referred to three main categories: (I) potential influences related to working
      conditions and practices of data collection, such as premature entry of the data
      (indicated by 85% of the respondents), competing duties (87%), and interfering
      interruptions or noise (67%); (II) problems referring to institutional management
      of the data, for example lacking feedback on the results (95%) and lacking
      knowledge about what the data are used for (75%); (III) problems related to
      specific attitudes, e.g., considering these data not useful for quality
      improvement (47%). Physicians were more sceptical than nurses regarding the
      relevance of these data for quality and patient safety. CONCLUSIONS: The common
      perceived difficulties reported by physician and nurse anaesthetists resemble
      established barriers to incident reporting and may similarly act as barriers to
      quality documentation during anaesthesia. Further studies should investigate if
      these perceived obstacles have a causal impact on quality reporting in
      anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier is NCT01524484.
      Registration date: January 21, 2012.

PMID- 25971792
TI  - All-trans retinoic acid mitigates methotrexate-induced liver injury in rats;
      relevance of retinoic acid signaling pathway.
AB  - Methotrexate (MTX) is a widely used drug for treatment of rheumatic and
      autoimmune diseases as well as different types of cancer. One of the major side
      effects of MTX is hepatotoxicity. Retinoid receptors, including retinoid X
      receptor (RXR), and retinoic acid receptor (RAR) are vitamin A receptors that are
      highly expressed in the liver and regulate important physiological processes
      through regulation of different genes. In this study, we investigated the effect
      of MTX on RXR-alpha and RAR-alpha expression in the liver and the potential
      protective effects of all-trans retinoic acid (ATRA) in MTX-induced
      hepatotoxicity. Rats were randomly divided into five groups: The rates were
      treated with saline, DMSO, MTX (20 mg/kg/IP; single dose), ATRA (7.5 mg/kg/day,
      I.P), or MTX and ATRA. Rats were killed 24 h after the last ATRA injection. The
      liver tissues were dissected out, weighed, and subjected to histological,
      immunohistochemical, and biochemical examinations. Our results demonstrated that
      treatment with MTX resulted in significant decrease in reduced glutathione (GSH)
      content and superoxide dismutase (SOD) activity, with concomitant increase in
      ALT, AST, and MDA levels. In addition, MTX markedly downregulated the expression
      of both RXR-alpha and RAR-alpha, and changed the appearance of RXR-alpha to be
      very small speckled droplets. Treatment with ATRA significantly ameliorated MTX
      induced effects on GSH, ALT, and MDA. Moreover, ATRA administration increased the
      expression and nuclear translocation of RXR-alpha in rat hepatocytes. In
      conclusion, our study revealed, for the first time, that retinoid receptors may
      play an important role in the MTX-induced hepatotoxicity. 

PMID- 25971793
TI  - Sesquiterpene lactone parthenolide attenuates production of inflammatory
      mediators by suppressing the Toll-like receptor-4-mediated activation of the Akt,
      mTOR, and NF-kappaB pathways.
AB  - Microbial product lipopolysaccharide has been shown to be involved in the
      pathogenesis of inflammatory skin diseases. Parthenolide present in extracts of
      the herb feverfew has demonstrated an anti-inflammatory effect. However, the
      effect of parthenolide on the Akt/mTOR and NF-kappaB pathway activation-induced
      productions of inflammatory mediators in keratinocytes has not been studied.
      Using human keratinocytes, we investigated the effect of parthenolide on the
      inflammatory mediator production in relation to the Toll-like receptor-4-mediated
      Akt/mTOR and NF-kappaB pathways, which regulate the transcription genes involved
      in immune and inflammatory responses. Parthenolide, Akt inhibitor, Bay 11-7085,
      and N-acetylcysteine each attenuated the lipopolysaccharide-induced production of
      IL-1beta and PGE2, increase in the levels of cyclooxygenase, formation of
      reactive oxygen species, increase in the levels of Toll-like receptor-4, and
      activation of the Akt/mTOR and NF-kappaB in keratinocytes. The results show that
      parthenolide appears to attenuate the lipopolysaccharide-stimulated production of
      inflammatory mediators in keratinocytes by suppressing the Toll-like receptor-4
      mediated activation of the Akt, mTOR, and NF-kappaB pathways. The activation of
      signaling transduction pathways appear to be regulated by reactive oxygen
      species. Parthenolide appears to attenuate the microbial product-mediated
      inflammatory skin diseases. 

PMID- 25971795
TI  - Assessing dose-response relationships for endocrine disrupting chemicals (EDCs):
      a focus on non-monotonicity.
AB  - The fundamental principle in regulatory toxicology is that all chemicals are
      toxic and that the severity of effect is proportional to the exposure level. An
      ancillary assumption is that there are no effects at exposures below the lowest
      observed adverse effect level (LOAEL), either because no effects exist or because
      they are not statistically resolvable, implying that they would not be adverse.
      Chemicals that interfere with hormones violate these principles in two important
      ways: dose-response relationships can be non-monotonic, which have been reported
      in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are
      often observed below the LOAEL, including all environmental epidemiological
      studies examining EDCs. In recognition of the importance of this issue, Lagarde
      et al. have published the first proposal to qualitatively assess non-monotonic
      dose response (NMDR) relationships for use in risk assessments. Their proposal
      represents a significant step forward in the evaluation of complex datasets for
      use in risk assessments. Here, we comment on three elements of the Lagarde
      proposal that we feel need to be assessed more critically and present our
      arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the
      concept of evaluating study quality without topical experts' knowledge and
      opinions, and 3) the requirement of establishing the biological plausibility of
      an NMDR before consideration for use in risk assessment. We present evidence
      based logical arguments that 1) the use of the Klimisch score should be abandoned
      for assessing study quality; 2) evaluating study quality requires experts in the
      specific field; and 3) an understanding of mechanisms should not be required to
      accept observable, statistically valid phenomena. It is our hope to contribute to
      the important and ongoing debate about the impact of NMDRs on risk assessment
      with positive suggestions.

PMID- 25971794
TI  - Immunoregulatory Effects of Paeoniflorin Exerts Anti-asthmatic Effects via
      Modulation of the Th1/Th2 Equilibrium.
AB  - Paeoniflorin has been demonstrated to exert anti-inflammatory and
      immunomodulatory effects in the animal study. In this study, we investigated
      immunoregulatory effects of paeoniflorin on anti-asthmatic effects and underlying
      mechanisms. Asthma model was established by ovalbumin-induced. A total of 50 mice
      were randomly assigned to five experimental groups: control, model, dexamethasone
      (2 mg/kg), and paeoniflorin (10 and 20 mg/kg). Airway resistance (Raw) were
      measured by the forced oscillation technique; histological studies were evaluated
      by the hematoxylin and eosin (HE) staining; Th1/Th2 cytokines were evaluated by
      enzyme-linked immunosorbent assay (ELISA); Th1/Th2 cells were evaluated by flow
      cytometry (FCM); and GATA3 and T-bet were evaluated by Western blot. Our study
      demonstrated that, compared with model group, paeoniflorin inhibited ovalbumin
      (OVA)-induced increases in Raw and eosinophil count; interleukin (IL)-4, IgE
      levels were recovered in bronchoalveolar lavage fluid compared; increased IFN
      gamma level in bronchoalveolar lavage fluid; histological studies demonstrated
      that paeoniflorin substantially inhibited OVA-induced eosinophilia in lung tissue
      and lung tissue compared with model group. Flow cytometry studies demonstrated
      that paeoniflorin can regulate Th1/Th2 balance. These findings suggest that
      paeoniflorin may effectively ameliorate the progression of asthma and could be
      used as a therapy for patients with allergic asthma. 

PMID- 25971796
TI  - Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V
      induced lung cancer by induction of telomeric DNA damage.
AB  - Telomeres are considered anti-cancer targets, as telomere maintenance above a
      minimum length is necessary for cancer growth. Telomerase abrogation in cancer
      prone mouse models, however, only decreased tumor growth after several mouse
      generations when telomeres reach a critically short length, and this effect was
      lost upon p53 mutation. Here, we address whether induction of telomere uncapping
      by inhibition of the TRF1 shelterin protein can effectively block cancer growth
      independently of telomere length. We show that genetic Trf1 ablation impairs the
      growth of p53-null K-Ras(G12V)-induced lung carcinomas and increases mouse
      survival independently of telomere length. This is accompanied by induction of
      telomeric DNA damage, apoptosis, decreased proliferation, and G2 arrest. Long
      term whole-body Trf1 deletion in adult mice did not impact on mouse survival and
      viability, although some mice showed a moderately decreased cellularity in bone
      marrow and blood. Importantly, inhibition of TRF1 binding to telomeres by small
      molecules blocks the growth of already established lung carcinomas without
      affecting mouse survival or tissue function. Thus, induction of acute telomere
      uncapping emerges as a potential new therapeutic target for lung cancer. 

PMID- 25971797
TI  - Spatial distribution of cell-cell and cell-ECM adhesions regulates force balance
      while main-taining E-cadherin molecular tension in cell pairs.
AB  - Mechanical linkage between cell-cell and cell-extracellular matrix (ECM)
      adhesions regulates cell shape changes during embryonic development and tissue
      homoeostasis. We examined how the force balance between cell-cell and cell-ECM
      adhesions changes with cell spread area and aspect ratio in pairs of MDCK cells.
      We used ECM micropatterning to drive different cytoskeleton strain energy states
      and cell-generated traction forces and used a Forster resonance energy transfer
      tension biosensor to ask whether changes in forces across cell-cell junctions
      correlated with E-cadherin molecular tension. We found that continuous peripheral
      ECM adhesions resulted in increased cell-cell and cell-ECM forces with increasing
      spread area. In contrast, confining ECM adhesions to the distal ends of cell-cell
      pairs resulted in shorter junction lengths and constant cell-cell forces. Of
      interest, each cell within a cell pair generated higher strain energies than
      isolated single cells of the same spread area. Surprisingly, E-cadherin molecular
      tension remained constant regardless of changes in cell-cell forces and was
      evenly distributed along cell-cell junctions independent of cell spread area and
      total traction forces. Taken together, our results showed that cell pairs
      maintained constant E-cadherin molecular tension and regulated total forces
      relative to cell spread area and shape but independently of total focal adhesion
      area. 

PMID- 25971799
TI  - VERY LONG CHAIN FATTY ACID SPHINGOMYELIN IN NUCLEAR LIPID MICRODOMAINS OF
      HEPATOCYTES AND HEPATOMA CELLS: CAN THE EXCHANGE FROM C24:0 TO C16:0 AFFECT
      SIGNAL PROTEINS AND VITAMIN D RECEPTOR?
AB  - Lipid microdomains localised in inner nuclear membrane are considered platforms
      for active chromatin anchoring. Stimuli as surgery, vitamin D or glucocorticoid
      drugs influence there gene expression, DNA duplication and RNA synthesis. Here,
      we used ultra fast liquid chromatography tandem mass spectrometry to identify
      sphingomyelin species coupled with immunoblotting analysis to comprehensively map
      differences in nuclear lipid microdomains purified from hepatocytes and hepatoma
      cells. We showed that nuclear lipid microdomains lost saturated very long fatty
      acid (C24:0) sphingomyelin in cancer cells and enriched in long fatty acid
      (C16:0) sphingomyelin. We also found that signaling proteins, such as STAT3,
      Raf1, and PKCzeta, were increased and Vitamin D receptor was reduced in cancer
      cells. Since recent researches showed a shift in sphingolipid composition from
      C24:0 to C16:0 in relation to cell life, we performed a comparative analysis of
      properties among C16:0 sphingomyelin, C24:0 sphingomyelin and cholesterol. Our
      results induced to hypothesise that the enrichment of C16:0 sphingomyelin could
      determine enhanced dynamic properties of nuclear lipid microdomains in cancer
      cells with an increased shuttling of proteins signaling molecules.

PMID- 25971798
TI  - Regulation of cell proliferation by ERK and signal-dependent nuclear
      translocation of ERK is dependent on Tm5NM1-containing actin filaments.
AB  - ERK-regulated cell proliferation requires multiple phosphorylation events
      catalyzed first by MEK and then by casein kinase 2 (CK2), followed by interaction
      with importin7 and subsequent nuclear translocation of pERK. We report that
      genetic manipulation of a core component of the actin filaments of cancer cells,
      the tropomyosin Tm5NM1, regulates the proliferation of normal cells both in vitro
      and in vivo. Mouse embryo fibroblasts (MEFs) lacking Tm5NM1, which have reduced
      proliferative capacity, are insensitive to inhibition of ERK by peptide and small
      molecule inhibitors, indicating that ERK is unable to regulate proliferation of
      these knockout (KO) cells. Treatment of wild-type MEFs with a CK2 inhibitor to
      block phosphorylation of the nuclear translocation signal in pERK resulted in
      greatly decreased cell proliferation and a significant reduction in the nuclear
      translocation of pERK. In contrast, Tm5NM1 KO MEFs, which show reduced nuclear
      translocation of pERK, were unaffected by inhibition of CK2. This suggested that
      it is nuclear translocation of CK2-phosphorylated pERK that regulates cell
      proliferation and this capacity is absent in Tm5NM1 KO cells. Proximity ligation
      assays confirmed a growth factor-stimulated interaction of pERK with Tm5NM1 and
      that the interaction of pERK with importin7 is greatly reduced in the Tm5NM1 KO
      cells. 

PMID- 25971800
TI  - The rod domain is not essential for the function of plectin in maintaining tissue
      integrity.
AB  - Epidermolysis bullosa simplex associated with late-onset muscular dystrophy (EBS
      MD) is an autosomal recessive disorder resulting from mutations in the plectin
      gene. The majority of these mutations occur within the large exon 31 encoding the
      central rod domain and leave the production of a low-level rodless plectin splice
      variant unaffected. To investigate the function of the rod domain, we generated
      rodless plectin mice through conditional deletion of exon 31. Rodless plectin
      mice develop normally without signs of skin blistering or muscular dystrophy.
      Plectin localization and hemidesmosome organization are unaffected in rodless
      plectin mice. However, superresolution microscopy revealed a closer juxtaposition
      of the C-terminus of plectin to the integrin beta4 subunit in rodless plectin
      keratinocytes. Wound healing occurred slightly faster in rodless plectin mice
      than in wild-type mice, and keratinocytes migration was increased in the absence
      of the rod domain. The faster migration of rodless plectin keratinocytes is not
      due to altered biochemical properties because, like full-length plectin, rodless
      plectin is a dimeric protein. Our data demonstrate that rodless plectin can
      functionally compensate for the loss of full-length plectin in mice. Thus the low
      expression level of plectin rather than the absence of the rod domain dictates
      the development of EBS-MD. 

PMID- 25971802
TI  - Identification of a Rab GTPase-activating protein cascade that controls recycling
      of the Rab5 GTPase Vps21 from the vacuole.
AB  - Transport within the endocytic pathway depends on a consecutive function of the
      endosomal Rab5 and the late endosomal/lysosomal Rab7 GTPases to promote membrane
      recycling and fusion in the context of endosomal maturation. We previously
      identified the hexameric BLOC-1 complex as an effector of the yeast Rab5 Vps21,
      which also recruits the GTPase-activating protein (GAP) Msb3. This raises the
      question of when Vps21 is inactivated on endosomes. We provide evidence for a Rab
      cascade in which activation of the Rab7 homologue Ypt7 triggers inactivation of
      Vps21. We find that the guanine nucleotide exchange factor (GEF) of Ypt7 (the
      Mon1-Ccz1 complex) and BLOC-1 both localize to the same endosomes. Overexpression
      of Mon1-Ccz1, which generates additional Ypt7-GTP, or overexpression of activated
      Ypt7 promotes relocalization of Vps21 from endosomes to the endoplasmic reticulum
      (ER), which is indicative of Vps21 inactivation. This ER relocalization is
      prevented by loss of either BLOC-1 or Msb3, but it also occurs in mutants lacking
      endosome-vacuole fusion machinery such as the HOPS tethering complex, an effector
      of Ypt7. Importantly, BLOC-1 interacts with the HOPS on vacuoles, suggesting a
      direct Ypt7-dependent cross-talk. These data indicate that efficient Vps21
      recycling requires both Ypt7 and endosome-vacuole fusion, thus suggesting
      extended control of a GAP cascade beyond Rab interactions. 

PMID- 25971801
TI  - Interaction of CK1delta with gammaTuSC ensures proper microtubule assembly and
      spindle positioning.
AB  - Casein kinase 1delta (CK1delta) family members associate with microtubule
      organizing centers (MTOCs) from yeast to humans, but their mitotic roles and
      targets have yet to be identified. We show here that budding yeast CK1delta,
      Hrr25, is a gamma-tubulin small complex (gammaTuSC) binding factor. Moreover,
      Hrr25's association with gammaTuSC depends on its kinase activity and its
      noncatalytic central domain. Loss of Hrr25 kinase activity resulted in assembly
      of unusually long cytoplasmic microtubules and defects in spindle positioning,
      consistent with roles in regulation of gammaTuSC-mediated microtubule nucleation
      and the Kar9 spindle-positioning pathway, respectively. Hrr25 directly
      phosphorylated gammaTuSC proteins in vivo and in vitro, and this phosphorylation
      promoted gammaTuSC integrity and activity. Because CK1delta and gammaTuSC are
      highly conserved and present at MTOCs in diverse eukaryotes, similar regulatory
      mechanisms are expected to apply generally in eukaryotes. 

PMID- 25971804
TI  - Implication of Industrial Waste for Biomass and Lipid Production in Chlorella
      minutissima Under Autotrophic, Heterotrophic, and Mixotrophic Grown Conditions.
AB  - Following the diminishing hopes from the first and second generation biofuels,
      mainly due to the limitations of land availability, feed stock requirements, and
      complicated pre-treatments, third generation biofuels from microalgae are
      becoming a priority in the current scenario. The present study focuses on
      comparison and optimization of lipid accumulation efficiency in algal strain
      Chlorella minutissima grown under autotrophic, heterotrophic, and mixotrophic
      modes of nutrition, employing various carbon sources obtained from cheap
      industrial wastes such as glucose, acetate, and glycerol. Other pertinent factors
      such as the effect of various nitrogen sources, effect of salinity on the cell
      growth, and lipid accumulations in the algal cells were also studied. The results
      suggested that C. minutissima can grow efficiently under autotrophic,
      heterotrophic, and mixotrophic modes of nutrition. C. minutissima cells were
      capable of utilizing other non-popular carbon sources such as glycerol and
      acetate collected as waste products from different industries along with commonly
      used glucose. The maximum biomass concentration (8.9 g/L) and lipid content
      (36.19 %) were found in heterotrophic mode of nutrition. Our findings indicated
      that C. minutissima can efficiently utilize these cheaper carbon sources from
      industrial waste products for its growth and the production cost of various
      bioenergy sources can be reduced significantly.

PMID- 25971803
TI  - A novel tropomyosin isoform functions at the mitotic spindle and Golgi in
      Drosophila.
AB  - Most eukaryotic cells express multiple isoforms of the actin-binding protein
      tropomyosin that help construct a variety of cytoskeletal networks. Only one
      nonmuscle tropomyosin (Tm1A) has previously been described in Drosophila, but
      developmental defects caused by insertion of P-elements near tropomyosin genes
      imply the existence of additional, nonmuscle isoforms. Using biochemical and
      molecular genetic approaches, we identified three tropomyosins expressed in
      Drosophila S2 cells: Tm1A, Tm1J, and Tm2A. The Tm1A isoform localizes to the cell
      cortex, lamellar actin networks, and the cleavage furrow of dividing cells-
      always together with myosin-II. Isoforms Tm1J and Tm2A colocalize around the
      Golgi apparatus with the formin-family protein Diaphanous, and loss of either
      isoform perturbs cell cycle progression. During mitosis, Tm1J localizes to the
      mitotic spindle, where it promotes chromosome segregation. Using chimeras, we
      identified the determinants of tropomyosin localization near the C-terminus. This
      work 1) identifies and characterizes previously unknown nonmuscle tropomyosins in
      Drosophila, 2) reveals a function for tropomyosin in the mitotic spindle, and 3)
      uncovers sequence elements that specify isoform-specific localizations and
      functions of tropomyosin.

PMID- 25971805
TI  - Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of
      cancer.
AB  - Various approaches of T-cell-based cancer immunotherapy are currently under
      investigation, among these are BiTE(r) (bispecific T-cell engager) antibody
      constructs, which have a unique design and mechanism of action. They are
      constructed by genetically linking onto a single polypeptide chain the minimal
      binding domains of monoclonal antibodies for tumor-associated surface antigens
      and for the T-cell receptor-associated molecule CD3. Concurrent engagement of the
      target cell antigen and CD3 leads to activation of polyclonal cytotoxic T-cells,
      resulting in target cell lysis. Blinatumomab, a BiTE targeting CD19, is being
      investigated in a broad range of B-cell malignancies and has recently been
      approved in the USA by the US FDA for Philadelphia chromosome-negative
      relapsed/refractory B-acute lymphoblastic leukemia under the trade name
      BLINCYTOTM. The BiTE platform is one of the clinically most advanced T-cell
      immunotherapy options. 

PMID- 25971806
TI  - Recovery of phosphate from the supernatant of activated sludge pretreated by
      microwave irradiation through chemical precipitation.
AB  - This paper presents a technology of releasing phosphate from activated sludge by
      using a combined process of microwave irradiation and anaerobic stirring,
      followed by phosphate recovery from the resulting supernatant via chemical
      precipitation without addition of chemicals, except for a pH regulator. A series
      of experiments was conducted to examine the effects of microwave irradiation
      time, sludge solution pH, sludge concentration, and anaerobic stirring time on
      the release of phosphate. The results revealed that all of these parameters had a
      significant effect on the release of phosphate via the proposed combined process,
      and the combination of 180 s of microwave irradiation and 1 h of anaerobic
      stirring was found to give optimal phosphate release. When the sludge solution
      was acidized before pretreatment, the phosphate concentration of the supernatant
      increased rapidly. A 25 g/L sludge concentration was found to be optimal for the
      release of phosphate, beyond this concentration, there was no increase in the
      phosphate release. Under the optimal conditions of phosphate release (irradiation
      time, 180 s; solution pH, 2; sludge concentration, 25 g/L; anaerobic stirring
      time, 1 h), the total orthophosphate (PT) concentration in the supernatant
      reached 396 mg/L, accompanied by high concentrations of metal cations such as Ca,
      Mg, K, Al, and Fe. When the pH of the supernatant was adjusted to 9-10, the
      recovery efficiency of phosphate reached approximately 95 %. The analysis results
      indicated that the main components of the collected precipitates were amorphous
      calcium phosphate and struvite, which can be used as alternate phosphate
      minerals.

PMID- 25971807
TI  - Changes in cellular energy allocation in Enchytraeus crypticus exposed to copper
      and silver--linkage to effects at higher level (reproduction).
AB  - Under stressful conditions, organisms often try to detoxify by mobilizing certain
      energy sources with costs to various functions, e.g. growth or reproduction.
      Cellular energy allocation (CEA) is a commonly used methodology to evaluate the
      energetic status of an organism. In the present study, the effects of copper (Cu)
      and silver (Ag) were evaluated on the total energy budget of Enchytraeus
      crypticus (Oligochaeta) over periods of exposure (0-2, 2-4 and 4-8 days). The
      parameters measured were the total energy reserves available (protein,
      carbohydrate and lipid budgets) and the energy consumption (based on electron
      transport system activity) being further integrated to obtain the CEA. Results
      showed that Enchytraeids responded differently to Ag and Cu, mobilizing lipids
      and proteins in response to Ag and carbohydrates and proteins in response to Cu.
      Overall, it was possible to distinguish between effect concentrations
      (reproduction effect concentrations-EC10 and EC50), with EC10 causing an increase
      in energy consumption (Ec); while for the EC50, the increase in Ec is followed by
      a steep decrease in Ec, with a corresponding decrease in CEA in the longer
      exposure periods. These results could be linked with effects at higher levels of
      biological organization (effects on reproduction) providing evidences that CEA
      can be used as faster and sensitive endpoints towards metal exposure in E.
      crypticus. 

PMID- 25971808
TI  - Characteristics and source identification of dissolved trace elements in the
      Jinshui River of the South Qinling Mts., China.
AB  - Dissolved trace elements and physiochemical parameters were analyzed to
      investigate their physicochemical characteristics and identify their sources at
      12 sampling sites of the Jinshui River in the South Qinling Mts., China from
      October 2006 to November 2008. The two-factor ANOVA indicated significant
      temporal variations of the dissolved Cu, Fe, Sr, Si, and V (p < 0.001 or p <
      0.05). With the exception of Sr (p < 0.001), no significant spatial variations
      were found. Distributions and concentrations of the dissolved trace elements
      displayed that dissolved Cu, Fe, Sr, Si, V, and Cr were originated from chemical
      weathering and leaching from the soil and bedrock. Dissolved Cu, Fe, Sr, As, and
      Si were also from anthropogenic inputs (farming and domestic effluents).
      Correlation and regression analysis showed that the chemical and physical
      processes of dissolved Cu was influenced by water temperature and dissolved
      oxygen (DO) to some degree. Dissolved Fe and Sr were affected by colloid
      destabilization or sedimentary inputs. Concentrations of dissolved Si were
      slightly controlled by biological uptake. Principal component analysis confirmed
      that Fe, Sr, and V resulted from domestic effluents, agricultural runoff, and
      confluence, whereas As, Cu, and Si were from agricultural activities, and Cr and
      Zn through natural processes. The research results provide a reference for
      ecological restoration and protection of the river environment in the Qinling
      Mts., China. 

PMID- 25971809
TI  - Physiological and biochemical responses and microscopic structure changes of
      Populus tomentosa Carr seedlings to 4-BDE exposure.
AB  - Populus species are very effective in remediation of contaminants. Polybrominated
      diphenyl ethers (PBDEs) are commonly used as flame retardants and are known to be
      persistent environmental pollutants. Numerous studies have shown that PBDEs are
      rising in human tissues and biota. 4-Monobrominated diphenyl ether (4-BDE), one
      of the less brominated PBDEs, was served as a model compound for biodegradation
      of lower brominated congeners. The present study was designed to clarify the
      effects of 4-BDE stress on morphological, physiological, and biochemical impacts
      of Populus tomentosa Carr in a tissue culture condition. Different concentrations
      of 4-BDE (3 and 30 mg L(-1)) were supplied alone or together with 0.5 mg L(-1)
      IBA in tissue culture media. With the concentration increased, 4-BDE caused
      negative effects on the microscopic structure of roots, stem, and leaves. The
      leaf color became shallow in low concentration of 4-BDE treatments and appeared
      albinism with 4-BDE concentration increased. The chlorophyll content and the leaf
      mass per area of albino leaves reduced significantly. 4-BDE also caused positive
      effects on the adventitious root differentiation and the biomass below 30 mg L(
      1). With the 4-BDE treatment time increased (23, 47, and 58 days), the peroxidase
      (POD) activity displayed the decreasing trend. The proline content decreased
      first and then increased. Exposure to 4-BDE induced the malondialdehyde (MDA) to
      increase in leaves. Application of 4-BDE affected the endogenous hormone levels
      of cuttings in their adventitious roots inducing media. Below 0.3 mg L(-1), 4-BDE
      caused the faint expression of auxin-sensitive DR5::GUS reporter gene in
      Arabidopsis thaliana. Additionally, P. tomentosa Carr exhibited the better
      tolerance against 4-BDE in the range of less than 30 mg L(-1). 

PMID- 25971810
TI  - Indoor mildew odour in old housing was associated with adult allergic symptoms,
      asthma, chronic bronchitis, vision, sleep and self-rated health: USA NHANES, 2005
      2006.
AB  - A recent systematic review and meta-analysis has shown the effect of indoor
      mildew odour on allergic rhinitis risk, but its relation to other common chronic
      health outcomes in adults has not been investigated. Therefore, it was aimed to
      examine the relationship of indoor mildew odour and common health outcomes in
      adults in a national and population-based setting. Data was retrieved from the
      United States National Health and Nutrition Examination Surveys, 2005-2006,
      including the available information on demographics, housing characteristics,
      self-reported health conditions and urinary concentrations of environmental
      chemicals. T test, chi-squared test and survey-weighted logistic regression
      modelling were performed. Of all American adults (n = 4979), 744 (15.1%) reported
      indoor mildew odour or musty smell in their households. People who reported
      indoor mildew odour or musty smell also reported poorer self-rated health, sleep
      complaints, chronic bronchitis, asthma attack, itchy rash, sneezing and poor
      vision. In addition, people who reported indoor mildew odour or musty smell also
      tended to reside in older housing that were built 20 years earlier. However,
      there were no significant statistical associations found between indoor mildew
      odour or musty smell and urinary concentrations of environmental chemicals, which
      was also found to be associated with old housing. People who lived in older
      housing with indoor mildew odour or musty smell tended to have chronic health
      problems. To protect occupants in old housing from chronic illnesses associated
      with indoor mildew odour, elimination of the odour sources should be explored in
      future research and therefore public health and housing programs. Graphical
      abstract Pathway from old housing to musty smell, environmental chemicals and
      then health outcomes.

PMID- 25971812
TI  - Visual search is influenced by 3D spatial layout.
AB  - Many activities necessitate the deployment of attention to specific distances and
      directions in our three-dimensional (3D) environment. However, most research on
      how attention is deployed is conducted with two dimensional (2D) computer
      displays, leaving a large gap in our understanding about the deployment of
      attention in 3D space. We report how each of four parameters of 3D visual space
      influence visual search: 3D display volume, distance in depth, number of depth
      planes, and relative target position in depth. Using a search task, we find that
      visual search performance depends on 3D volume, relative target position in
      depth, and number of depth planes. Our results demonstrate an asymmetrical
      preference for targets in the front of a display unique to 3D search and show
      that arranging items into more depth planes reduces search efficiency. Consistent
      with research using 2D displays, we found slower response times to find targets
      in displays with larger 3D volumes compared with smaller 3D volumes. Finally, in
      contrast to the importance of target depth relative to other distractors, target
      depth relative to the fixation point did not affect response times or search
      efficiency. 

PMID- 25971813
TI  - Effects of cluster location and cluster distribution on performance on the
      traveling salesman problem.
AB  - Research on human performance in solving traveling salesman problems typically
      uses point sets as stimuli, and most models have proposed a processing stage at
      which stimulus dots are clustered. However, few empirical studies have
      investigated the effects of clustering on performance. In one recent study,
      researchers compared the effects of clustered, random, and regular stimuli, and
      concluded that clustering facilitates performance (Dry, Preiss, & Wagemans,
      2012). Another study suggested that these results may have been influenced by the
      location rather than the degree of clustering (MacGregor, 2013). Two experiments
      are reported that mark an attempt to disentangle these factors. The first
      experiment tested several combinations of degree of clustering and cluster
      location, and revealed mixed evidence that clustering influences performance. In
      a second experiment, both factors were varied independently, showing that they
      interact. The results are discussed in terms of the importance of clustering
      effects, in particular, and perceptual factors, in general, during performance of
      the traveling salesman problem. 

PMID- 25971811
TI  - The unusual suspects--innate lymphoid cells as novel therapeutic targets in IBD.
AB  - Innate lymphoid cells (ILCs) are a family of immune cells that selectively
      accumulate in mucosal tissues serving as sentinels at the vanguard of host
      protective immunity. However, they are also implicated as cellular mediators of
      immune-mediated diseases, most notably IBD. ILCs are subdivided into distinct
      lineages based on the expression of effector cytokines and master transcription
      factors that programme their differentiation and inflammatory behaviour.
      Strikingly, these subsets closely resemble CD4(+) T-cell lineages, including T
      helper (TH)1, TH2 and TH17 cells that are similarly implicated in immune-mediated
      diseases. However, ILCs that promote the maintenance of intestinal epithelial
      cells, mostly through production of IL-22, also exist. ILCs rapidly respond to
      environmental cues, including cytokines, metabolic signals and luminal bacteria.
      They are potent and immediate producers of key cytokines linked to IBD
      pathogenesis, including TNF, IL-17, IL-22 and IFN-gamma. Some subsets are
      implicated as mediators of chronic intestinal inflammation, whereas others might
      provide protective functions. They are present in the gut of patients with IBD
      and, intriguingly, closer scrutiny of IBD susceptibility loci shows that many of
      these genes are either expressed by, or are intimately linked to, ILC function.
      Looking forward, targeting ILCs could represent a new IBD treatment paradigm. 

PMID- 25971814
TI  - Reactivity pattern of bromonucleosides induced by 2-hydroxypropyl radicals:
      photochemical, radiation chemical, and computational studies.
AB  - The bromonucleosides (BrdX's) 5-bromo-2'-deoxyuridine (BrdU), 5-bromo-2'
      deoxycytidine (BrdC), 8-bromo-2'-deoxyadenosine (BrdA), and 5-bromo-2'
      deoxyguanosine (BrdG) may substitute for ordinary nucleosides in DNA. As
      indicated by electron-stimulated desorption experiments, such a modified
      biopolymer is greater than 2-3-fold more sensitive to damage induced by excess
      electrons. The other major product of water radiolysis, the (*)OH radical, may
      form a number of other radicals in chemical reactions with the complex content of
      the cell. Thus, the well-proved BrdU-labeled DNA radiosensitivity may be, at
      least in part, related to secondary organic radicals. Therefore, in the current
      study, the propensity of BrdX's to damage induced by 2-hydroxypropyl radical
      (OHisop(*))-a prototype radical species-was investigated. The HPLC and LC-MS
      analyses revealed the formation of two major products from the brominated
      pyrimidine nucleosides, a native nucleoside and an adduct of BrdX and OHisop(*) ,
      and only an adduct of BrdX from the bromopurine nucleosides. Quantum chemical
      calculations ascribed this evident difference between purines and pyrimidines to
      the electron transfer from OHisop(*) to BrdX that is especially favorable in
      pyrimidines. 

PMID- 25971815
TI  - Effect of omega-3 polyunsaturated fatty acids on the cytoskeleton: an open-label
      intervention study.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) show beneficial
      effects on cardiovascular health and cognitive functions, but the underlying
      molecular mechanisms are not completely understood. Because of the fact that
      cytoskeleton dynamics affect almost every cellular process, the regulation of
      cytoskeletal dynamics could be a new pathway by which n-3 PUFAs exert their
      effects on cellular level. METHODS: A 12-week open-label intervention study with
      12 healthy men was conducted to determine the effects of 2.7 g/d n-3 PUFA on
      changes in mRNA expression of cytoskeleton-associated genes by quantitative real
      time PCR in whole blood. Furthermore, the actin content in red blood cells was
      analyzed by immunofluorescence imaging. RESULTS: N-3 PUFA supplementation
      resulted in a significant down-regulation of cytoskeleton-associated genes, in
      particular three GTPases (RAC1, RHOA, CDC42), three kinases (ROCK1, PAK2, LIMK),
      two Wiskott-Aldrich syndrome proteins (WASL, WASF2) as well as actin related
      protein 2/3 complex (ARPC2, ARPC3) and cofilin (CFL1). Variability in F-actin
      content between subjects was high; reduced actin content was only reduced within
      group evaluation. CONCLUSIONS: Reduced cytoskeleton-associated gene expression
      after n-3 PUFA supplementation suggests that regulation of cytoskeleton dynamics
      might be an additional way by which n-3 PUFAs exert their cellular effects.
      Concerning F-actin, this analysis did not reveal unmistakable results impeding a
      generalized conclusion.

PMID- 25971816
TI  - KnowLife: a versatile approach for constructing a large knowledge graph for
      biomedical sciences.
AB  - BACKGROUND: Biomedical knowledge bases (KB's) have become important assets in
      life sciences. Prior work on KB construction has three major limitations. First,
      most biomedical KBs are manually built and curated, and cannot keep up with the
      rate at which new findings are published. Second, for automatic information
      extraction (IE), the text genre of choice has been scientific publications,
      neglecting sources like health portals and online communities. Third, most prior
      work on IE has focused on the molecular level or chemogenomics only, like protein
      protein interactions or gene-drug relationships, or solely address highly
      specific topics such as drug effects. RESULTS: We address these three limitations
      by a versatile and scalable approach to automatic KB construction. Using a small
      number of seed facts for distant supervision of pattern-based extraction, we
      harvest a huge number of facts in an automated manner without requiring any
      explicit training. We extend previous techniques for pattern-based IE with
      confidence statistics, and we combine this recall-oriented stage with logical
      reasoning for consistency constraint checking to achieve high precision. To our
      knowledge, this is the first method that uses consistency checking for biomedical
      relations. Our approach can be easily extended to incorporate additional
      relations and constraints. We ran extensive experiments not only for scientific
      publications, but also for encyclopedic health portals and online communities,
      creating different KB's based on different configurations. We assess the size and
      quality of each KB, in terms of number of facts and precision. The best
      configured KB, KnowLife, contains more than 500,000 facts at a precision of 93%
      for 13 relations covering genes, organs, diseases, symptoms, treatments, as well
      as environmental and lifestyle risk factors. CONCLUSION: KnowLife is a large
      knowledge base for health and life sciences, automatically constructed from
      different Web sources. As a unique feature, KnowLife is harvested from different
      text genres such as scientific publications, health portals, and online
      communities. Thus, it has the potential to serve as one-stop portal for a wide
      range of relations and use cases. To showcase the breadth and usefulness, we make
      the KnowLife KB accessible through the health portal (http://knowlife.mpi
      inf.mpg.de).

PMID- 25971817
TI  - Rising prevalence of diabetes mellitus in Saudi Arabia: cause for concern and
      call for urgent control program.

PMID- 25971818
TI  - The Saudi Abnormal Glucose Metabolism and Diabetes Impact Study (SAUDI-DM).
AB  - BACKGROUND AND OBJECTIVES: Saudi Arabia underwent opulence-driven socio-cultural
      and lifestyle changes leading to soaring rates of diabetes mellitus. This study
      exposes the epidemiology of abnormal glucose metabolism namely: diabetes and
      impaired fasting glucose (IFG) in 13 administrative regions of Saudi Arabia.
      DESIGN AND SETTINGS: This is a nationwide, household, population-based cross
      sectional study that was conducted through primary health care centers during the
      period 2007-2009. PATIENTS AND METHODS: A nationwide, household, population-based
      cohort of 53370 participants aged 0-100 years adjusted to be compatible with
      population census was interviewed and anthropometric measures were collected.
      Fasting blood sample was used to screen for IFG and diabetes. RESULTS: The
      overall prevalence of abnormal glucose metabolism was 34.5%, which included 22.6%
      patients with IFG, 11.9% patients with diabetes, and 6.2% patients who unaware of
      their disease. Diabetes prevalence was 40.2% for subjects aged >=45 years and
      25.4% for those aged >=30 years that decreased to 11.9% when the full age
      spectrum was considered. Type 1 diabetes prevalence was 0. 8%, contributing only
      to 6.6% of the total population of patients with diabetes. The top 5 regions with
      the highest abnormal glucose metabolism prevalence were Makkah (43.4%), Aljouf
      (41.7%), Eastern region (37.16%), Madinah (35.4%), and Qassim (33.7%).
      Urbanization, age, and obesity were behind the wide variations in diabetes and
      IFG prevalence in the 13 regions. CONCLUSION: Abnormal glucose metabolism has
      reached an epidemic state in Saudi Arabia, where one-third of the population is
      affected and half of diabetic cases were unaware of their disease. This
      observation warrants an urgent strategy for launching diabetes primary prevention
      and screening programs.

PMID- 25971819
TI  - Insulin resistance using HOMA model in obstructive sleep apnea: a cross sectional
      study.
AB  - BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is a common disease
      affecting middle-aged patients and is associated with significant cardiovascular,
      cerebrovascular, and metabolic complications. Current evidences show inconclusive
      association between OSA and insulin resistance (IR). This study aims to examine
      the possible correlation between OSA parameters and IR. DESIGN AND SETTINGS: This
      was a cross-sectional study to examine the association between OSA parameters and
      IR using homeostasis model assessment (HOMA) on patients who underwent
      polysomnogram (PSG) in a tertiary center between March 2011 and March 2012 (1
      year). PATIENTS AND METHODS: A total of 62 patients underwent PSG within the
      study period, of which 16 patients were excluded due to abnormal fasting blood
      sugar. Information on patients' medical illnesses, medications, and Epworth
      sleepiness scale (ESS) was obtained. Patients' body mass index (BMI), neck
      circumference, and waist circumference (WC) were measured. Blood samples were
      collected after 8 hours of fasting to measure HOMA-IR value. Overnight PSG was
      performed for all patients. Data was recorded and analyzed using SPSS, version
      12.0 (SPSS Inc, Chicago, USA). RESULTS: The prevalence of IR in OSA patients was
      64.3%. There was significant correlation between OSA parameters (apnea-hypopnea
      index, ESS, BMI, and WC) and HOMA-IR with correlation coefficient of 0.529,
      0.224, 0.261, and 0.354, respectively. CONCLUSION: A linear correlation exists
      between OSA parameters and IR concluding a definite causal link between OSA and
      IR. IR screening is recommended in severe OSA patients.

PMID- 25971820
TI  - Quality of care in primary percutaneous coronary intervention for acute ST
      segment -elevation myocardial infarction: Gulf RACE 2 experience.
AB  - BACKGROUND AND OBJECTIVES: Primary percutaneous coronary intervention (pPCI) has
      been recognized as an effective management strategy for acute ST-segment
      elevation myocardial infarction (STEMI). However, there is no first-hand
      information regarding the quality of pPCI procedures in the Arabian Gulf
      countries. This study aims to explore the quality of pPCI practice. DESIGN AND
      SETTINGS: The Gulf Race II was designed as a prospective, multinational,
      multicentre registry of acute coronary events, focusing on the epidemiology,
      management practices, and outcomes of patients with acute coronary syndrome. The
      study recruited consecutive patients aged 18 years and above from 65 hospitals in
      6 adjacent Middle Eastern countries (Bahrain, Saudi Arabia, Qatar, Oman, United
      Arab Emirates, and Yemen). PATIENTS AND METHODS: We used data from the Gulf
      Registry of Acute Coronary Events (Gulf RACE 2). We analyzed data on patients who
      received pPCI to assess the guidelines-supported performance measure of door-to
      balloon (D2B).

PMID- 25971821
TI  - Quality of medical management in coronary artery disease.
AB  - BACKGROUND AND OBJECTIVES: Patients with coronary artery disease (CAD) are at
      high risk of recurrent adverse cardiac events. Such risk can be diminished
      through a guideline-recommend optimal medical therapy (OMT), defined as adherence
      to appropriate antiplatelet therapy, lipid-lowering agents, beta-blockers and
      angio.tensin-converting enzyme inhibitors, blood pressure < 140/90 mm Hg ( <
      130/80 mm Hg in diabetics and renal disease patients), low-density lipoprotein
      (LDL) < 2 mmol/L, smoking cessation and aerobic physical activity, and hemoglobin
      (Hb) A1c < 7%. Unfortunately, preliminary data suggest a wide gap between
      recommended and actual practices. The study aims to estimate the rate of
      achieving of OMT in CAD patients in Qassim Province. DESIGN AND SETTINGS: This
      observational study enrolled 207 consecutive CAD patients seen in cardiology
      clinic in Prince Sultan Cardiac Center in Qassim between January 2012 and May
      2012. METHODS: Eligible participants were over the age of 18, with CAD documented
      by either noninvasive testing or by coronary angiogram. We collected the
      demographic, medications, laboratory, and clinical data through in-person
      interviews, medical records, and an electronic patient database. RESULTS: OMT was
      achieved in only 10.4% of CAD patients. The rate of achievement of target
      systolic blood pressure was 76.5%, target diastolic blood pressure 88%, target
      LDL 68%, adherence to medications 91%. Diabetes was common (64% of all patients),
      and only 24% of these patients achieved the target HbA1c. CONCLUSION: The poor
      achievement of optimal medical therapy in CAD patients contributes to
      prevent.able mortality, morbidity, and health care costs. The observed
      shortcomings warrant investment in strategies to achieve OMT in these high-risk
      patients.

PMID- 25971822
TI  - The short- and long-term effect of Blalock-Taussig shunt size on the outcome
      after first palliative surgery for cyanotic heart diseases.
AB  - BACKGROUND AND OBJECTIVES: The Blalock-Taussig (BT) shunt is regarded a safe and
      effective means increasing pulmonary blood flow for cyanotic heart conditions.
      The evaluation of shunt size for postoperative hemodynamics and until second
      stage palliation remains difficult. Our objective is to compare the effect of
      different shunt sizes on short- and long-term outcomes after a BT shunt surgery.
      DESIGN AND SETTINGS: This is a retrospective review in a tertiary care hospital.
      PATIENTS: The records of all patients with a modified BT shunt between January
      2007 and January 2010 were reviewed. METHODS: Patients were divided into 2
      groups: Group A with a BT shunt of 3.5 mm and Group B with a BT shunt of 4 mm,
      and their body weight was less than 4 kg. Groups were compared for the short-term
      outcome, which includes: intensive care unit course, intensive care unit (ICU)
      and hospital stay, mortality during the same admission, and the size of branch
      pulmonary arteries (PAs) before second surgery. RESULTS: A total of 29 (42%)
      patients were in Group A and 40 (58%) in Group B. There was no significant
      difference in the mean weight between both groups; P value .06. There was no
      significant difference between the 2 groups in regard to diastolic blood pressure
      and lactate levels by the end of the first 48 hours after surgery. Group A
      required longer duration of inotropes and more days of ventilation with P value
      .03 and .001, respectively. The mean (standard deviation) ICU and hospital stay
      were 10.0 (8.9) days and 17.0 (11.4) days, respectively, for Group A and 12 (8.9)
      days and 15 (12.9) days, respectively, for Group B with P value .7 and P value
      .6, respectively. Yet Group B had a better branch PA size and required lesser
      intervention for branch PAs in comparison to Group A. CONCLUSION: These data
      suggest that a smaller shunt size may have a trend toward higher morbidity. A
      bigger shunt size does not necessarily lead to stealing phenomena and its
      consequences, and can be performed with a low risk leading to a better growth of
      branch PAs.

PMID- 25971823
TI  - Repair of congenital diaphragmatic hernia under high-frequency oscillatory
      ventilation in high-risk patients: an opportunity for earlier repair while
      minimizing lung injury.
AB  - BACKGROUND: Repair of congenital diaphragmatic hernia (CDH) is ideally delayed
      until ventilatory parameters are stabilized and patients are switched to
      conventional ventilation. However, in selected high-risk patients, repair can be
      performed earlier while they are still on high-frequency oscillatory ventilation
      (HFOV). DESIGN AND SETTINGS: A retrospective review of all CDH cases treated in
      our tertiary referral center between 1997 and 2013. METHODS: In 1997, we started
      repairing selected high-risk CDH cases under HFOV with or without inhaled nitric
      oxide (iNO). All repairs were performed once the infants' blood gas levels were
      acceptable. The infants were gradually weaned to conventional ventilation
      followed by extubation as their ventilatory parameters improved. Their records
      were reviewed to determine the group-wide outcomes. RESULTS: Between 1997 and
      2013, 55 infants with CDH were treated in our institute; of these 12 high-risk
      cases were repaired under HFOV/iNO combinations and 1 was repaired without iNO.
      All patients had significant pulmonary hypertension and 8 had herniated livers.
      The mean age at repair was 9.1 (6.3) days. Two mortalities occurred at the first
      and tenth postoperative days. Among the remaining 11 survivors, the median
      ventilation and hospitalization days were 29.5 (11-84) and 45.5 (25-107),
      respectively, and the median duration under HFOV and conventional ventilation
      days were 15 (9-40) and 12 (3-47), respectively. CONCLUSION: CDH repair can be
      performed earlier under HFOV and iNO. The possible advantages are earlier
      restoration of normal anatomy and earlier start of enteral feeding while
      minimizing the risk of lung injury.

PMID- 25971824
TI  - Association of HLA-DR/DQ polymorphisms with schizophrenia in Tunisian patients.
AB  - BACKGROUND AND OBJECTIVES: The hypothesis that human leukocyte antigens (HLAs)
      confer susceptibility to schizophrenic disorders has been tested by studying
      linkage and association in family samples. Our goal was to evaluate the role of
      HLA in the risk of developing schizophrenia in a Tunisian population. DESIGN AND
      SETTINGS: Blood samples for this case-control study were collected from patients
      of the Department of Psychiatry at the Military Hospital of Tunisia between July
      2012 and May 2013. METHODS: A total of 140 patients with schizophrenia were
      recruited for genetic analysis. Controls included 100 persons matched for age,
      sex, and risk factors. Participants were tested for HLA class II alleles. HLA
      DRB1 and HLA-DQB1 alleles were genotyped using polymerase chain reaction sequence
      specific primers. RESULTS: This study indicates that the alleles most responsible
      for disease susceptibility are DRB1*03 (P < 10-3) and DQB1*02 (P < 10-3) (P
      denotes probability values). The most protective alleles are DRB1*13 (P=.013) and
      DQB1*05 (P < 10-3). Further results revealed that DRB1*0301/DQB1*0201(P < 10-3),
      DRB1*0401/DQB1*0301 (P < 10-3) and DRB1*1101/DQB1*0301 (P < 10-3) are haplotypes
      most conducive to disease susceptibility. CONCLUSION: The present findings
      support an association between schizophrenia and the HLA-DR-DQ locus among a
      Tunisian population. To our knowledge, this is the first study performed to
      analyze the association of HLA DRB1/DQB1 alleles on schizophrenia susceptibility
      in Tunisia.

PMID- 25971825
TI  - Clinical characterization of unusual cystic echinococcosis in southern part of
      Turkey.
AB  - BACKGROUND AND OBJECTIVES: The incidence of primary extrahepatic cystic
      echinococcosis (CE) is rare. Generally, radiological and serological findings can
      help establish the diagnosis of hepatic and pulmonary CE, but a CE in an unusual
      location with atypical radiological findings may complicate the differential
      diagnosis. The objective of this study is to present the characteristics of cases
      with extrahepatic CE in respect of sites of involvement, clinical presentations,
      radiological findings, serological diagnostic evaluations, and outcomes of
      infected patients. DESIGN AND SETTINGS: A retrospective analysis of surgically
      treated CE was conducted between January 1993 and January 2014 in the General
      Surgery, Pediatric Surgery, Urology, Cardiovascular Surgery, Neurosurgery, and
      Orthopedics departments of University of Cukurova, Faculty of Medicine, Balcal
      Hospital. PATIENTS AND METHODS: Among the 661 patients managed for CE, 134 had
      unusual sites of involvement. Radiological and serological examinations were used
      to differentiate CE from alveolar echinococcosis. RESULTS: Of 134 cases with
      unusual sites of involvement, 32 cases had liver CE (23.9%), 7 cases had lung CE
      (5.2%), and 2 cases had concomitant liver and lung CE (1.5%). In 93 (69.4%)
      cases, unusual organ involvement was isolated without any liver or lung
      involvement. The mean age was 45 years. Abdominal pain was the main symptom and
      was found in 104 patients. Thirty-one (23.1%) of 134 extrahepatic CE cases were
      evaluated as negative with indirect hemagglutination (IHA). However, positive
      results were obtained in 54 cases evaluated with Echinococcus granulosus IgG
      Western blot (WB), including 10 IHA-negative cases. CONCLUSION: CE with unusual
      localizations may cause serious problems of diagnostic confusion. The combination
      of clinical history, radiological findings, and serological test results
      (especially the WB) are valuable in diagnosing extrahepatic CE.

PMID- 25971826
TI  - Disruptive behavior in Down syndrome children: a cross-sectional comparative
      study.
AB  - BACKGROUND AND OBJECTIVES: Down syndrome (DS) is associated with intellectual
      disability, and patients with DS show significant psychopathology. The objectives
      of this study were to estimate the prevalence of disruptive behavior in DS
      patients compared to their siblings, and to find any association between the
      disruptive behavior and the degree of intelligence. DESIGN AND SETTINGS: This is
      a cross-sectional comparative study done in Mansoura University Children's
      Hospital during the period March 1, 2012-February 28, 2013. SUBJECTS AND METHODS:
      In this study, 100 cases of DS and an equal number of their brothers/sisters were
      enrolled in the study. The Arabic version of Vineland Adaptive Behavior Scale was
      used for assessing social and mental intelligence quotient (IQ). The Arabic
      version of Mini International Neuropsychiatric Interview for Children (MINI-KID)
      and disruptive behavior disorder (DBD) rating scale were used for assessing
      disruptive behavior disorders. RESULTS: Both social and mental IQs were
      significantly higher in non-DS than in DS cases. The prevalence of different
      variants of attention deficit/hyperactive disorder (ADHD)-impulsive, inattentive,
      and combined types-was significantly lower in non-DS than in DS cases; however,
      there was no statistical difference between both groups as regards oppositional
      defiant disorder and conduct disorder (CD). Also among DS cases, impulsive and
      combined types varied significantly with the degree of their IQ. CONCLUSION: ADHD
      was more common among DS patients with a special impact of IQ on the type of
      psychiatric illness. We recommend psychiatric assessment for DS patients as a
      part of multidisciplinary management.

PMID- 25971827
TI  - Comparison of the results of ultrasonographic evaluation and arthroscopy in
      patients scheduled for surgery of the supraspinatus tendon rupture.
AB  - BACKGROUND AND OBJECTIVES: This study aims to compare the findings of the
      shoulder ultrasonography (US) of patients with a supraspinatus (SS) tendon
      rupture with those of the shoulder arthroscopy, to determine the reliability and
      diagnostic performance of the shoulder US in the algorithm of the SS tendon
      pathologic lesions and their secondary ultrasonographic findings. DESIGN AND
      SETTINGS: A prospective study conducted with patients scheduled for arthroscopy
      of the shoulder due to an SS tendon rupture in Yildirm Beyazit Education and
      Research Center and Gazi University, Ankara, Turkey. MATERIALS AND METHODS: Fifty
      patients scheduled for an arthroscopy of the shoulder due to an SS tendon rupture
      were evaluated by shoulder US 1 week before the surgery. SS tendon pathologic
      lesions (tendinosis, partial tears, and full-thickness tears) and humeral
      degeneration were recorded, and the results of shoulder US were compared with
      those of arthroscopy. RESULTS: With reference to the arthroscopic data, the
      sensitivity of the ultrasonographic evaluation for the diagnosis of a full
      thickness SS tendon rupture was 91%, with a specificity of 88%; the sensitivity
      for the diagnosis of a partial-thickness rupture was 86%, with a specificity of
      82%; and the sensitivity for the diagnosis of a tendinosis was 98%, with a
      specificity of 71%. With reference to the arthroscopic data, the sensitivity of
      US for the diagnosis of humeral degeneration was 93%, with a specificity of 91%.
      CONCLUSION: The high sensitivity and specificity rates of US in detecting SS
      tendon rupture and its secondary imaging findings make it an efficient and
      reliable diagnostic modality, which should be preferred to other more expensive
      and more invasive methods in the algorithm.

PMID- 25971828
TI  - Waugh syndrome: a report of 7 patients and review of the published reports.
AB  - BACKGROUND AND OBJECTIVES: Waugh syndrome (WS) is the association of
      intussusception and intestinal malrotation. The association is rarely reported in
      the literature though intussusception is a commonly encountered problem in
      pediatric patients as a cause of intestinal obstruction. We present our
      experience in 7 patients with a review of published reports. DESIGN AND SETTING:
      Retrospective analysis of 7 patients with the diagnosis of Waugh syndrome who
      were treated at our department between February 1982 to December 2012. PATIENTS
      AND METHODS: Seven patients with Waugh syndrome presented to our unit during the
      period February 1982 to December 2012. The clinical findings and management are
      presented and discussed. RESULTS: Seven patients (three males and four females)
      presented with intussusception in association with mal.rotation. The age range
      was from 4 to 11 months; the patients had bilious vomiting and blood in the
      stool; the diagnosis was confirmed by ultrasound (2), Ba enema (2) and
      intraoperatively (3). All required operative intervention; either manual
      reduction or bowel resection and Ladd procedure; one patient died of sepsis;
      recurrence of obstruction was seen in another patient while the rest did well
      postoperatively. CONCLUSION: The relationship between intestinal malrotation and
      intussusceptions may be more frequent than is reported; failure of non-operative
      management of intussusception may be due to this association and hence brings the
      attention to its existence. A prospective study is needed to look for intestinal
      malrotation in patient with intussusceptions who undergo abdominal sonographic
      examination to determine the true incidence of this association. The anomaly is
      suspected by presence of a reversed anatomic relationship of the superior
      mesenteric artery and vein and in such cases to perform an upper gastrointestinal
      contrast study to define the exact location of the duodenojejuonal (DJ).

PMID- 25971829
TI  - The deep hypothermic circulatory arrest causes more kidney malfunctions based on
      a novel rabbit model.
AB  - BACKGROUND AND OBJECTIVES: High incidences of acute kidney injury after
      cardiopulmonary bypass (CPB) were observed in previous reports. However, whether
      deep hypothermic circulatory arrest (DHCA) leads to more severe kidney injury
      than CPB without DHCA remains controversial. The aim of the study was to
      investigate the effects of DHCA on renal function in a novel rabbit model of
      using closed-thoracic DHCA. DESIGN AND SETTINGS: Experimental study on New
      Zealand white rabbits performed in the Department of Cardiac Surgery, the First
      Affiliated Hospital of China Medical University. METHODS: Thirty rabbits were
      randomly divided into 3 groups : the sham-operated group (Group A, N=10), the CPB
      group (Group B, N=10), and the DHCA group (Group C, N=10). Serum creatinine
      (Scr), blood urea nitrogen (BUN), serum cystatin C, neutrophil gelatinase
      associated lipocalin (NGAL), malondialdehyde (MDA) levels, superoxide dismutase
      (SOD) activities, histopathologic llesions, and apoptosis were assessed. RESULTS:
      Each single rabbit in Groups B and C died during surgery. Animals received DHCA
      exhibited more severe kidney impairments than those received CPB and those that
      were sham operated. Scr and BUN concentrations at 24 and 48 hours after surgery;
      cystatin C and NGAL concentrations at 12, 24, and 48 hours after surgery; MDA
      levels, histopathological lesions, and apoptosis score of the kidneys were the
      highest in Group C, followed by Group B, and were the lowest in Group A (all P <
      .05). The activities of SOD were the lowest in Group C, followed by Group B, and
      were the highest in Group A (P < .05). CONCLUSION: Our study established a
      simple, convenient, economical, and long-term surviving rabbit model for the
      study of DHCA-induced organic injury. Based on more significant kidney injuries,
      including elevated levels of serum cystatin C and NGAL at an early time,
      increased lipid peroxidation, decreased renal antioxidative ability, enhanced
      histological lesions, and increased tubular epithelial apoptosis from DHCA
      animals, we concluded that DHCA has more kidney dysfunctions than CPB without
      DHCA.

PMID- 25971830
TI  - Postpartum hepatotoxicity due to herbal medicine Teucrium polium.
AB  - The hepatotoxicity cases due to herbal medical products have been increased in
      recent years. Teucrium polium (TP) (mountain germander) is one of the most
      popular species of the Lamiaceae family and is commonly used for increasing
      breast milk formation and for relieving gastrointestinal complaints in the last
      months of pregnancy and postpartum periods. Here are presented 3 cases of serious
      hepatotoxicity due to TP. Three female patients aged 33, 31, and 37 years were
      admitted to clinic with jaundice and serious elevated liver enzymes for a period
      of 2 years. The patients were using TP for approximately 40 days to 3 months. Two
      of the 3 used TP during their previous pregnancies and were monitored for similar
      complaints by another center. After discontinuation of TP and supportive care,
      the liver function tests were decreased to normal limits within 3 months in all 3
      patients. In addition to the potential hepatotoxic effect of TP, physiological
      changes in the postpartum period may increase the severity of hepatotoxicity. TP
      should be considered in differential diagnosis in patients presenting similar
      history and complaints, where it is used commonly. 

PMID- 25971831
TI  - Solitary intestinal myofibroma an unusual cause of neonatal intestinal
      obstruction.
AB  - Congenital solitary myofibroma is an exceptional tumor of newborn period and
      presents as solitary or multiple lesions usually confined to soft tissues. It
      induces intestinal obstruction or perforation, which most frequently involves the
      jejunum and ileum. However, jejunoileal atresia is the most frequently
      encountered cause of small bowel obstruction in the neonatal period. We report a
      new case of solitary myofibroma located in the wall of the ileum, measuring 2.3
      cm2 in size, about 25 cm from the ileocecal junction, in a 17-day-old baby girl
      who presented with abdominal distention and bilious vomiting. Laparotomy was
      performed on the patient and the tumor was removed; the patient did well after
      surgery. Despite all the common causes of intestinal obstruction-intestinal
      atresia, Hirschsprung disease, anorectal anomaly, malrotation, and meconium
      passage problem in the neonatal period-myofibroma of the small bowel has to be
      considered because treatment is fairly easy and prognosis is excellent. 

PMID- 25971832
TI  - Melorheostosis mimicking synovial osteochondromatosis.
AB  - Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect
      the adjacent soft tissues. It has been associated with many entities such as
      osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors,
      nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and
      mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of
      the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint
      or tendon sheath. The intra-articular extension of melorheostosis mimicking
      synovial osteochondromatosis has not been reported before. In this article, the
      authors describe an unusual case mimicking synovial chondromatosis arising as a
      result of melorheostosis and their characteristic imaging findings.

PMID- 25971833
TI  - Anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma (ALCL)
      of breast in a patient without a breast implant.
AB  - Non-Hodgkin lymphoma of the breast is an uncommon entity accounting for
      approximately 0.5% of malignant breast neoplasms and around 3% of extranodal
      lymphomas. Most cases of anaplastic large cell lymphoma (ALCL) of the breast have
      been associated with breast implants, and a few ALCL aris.ing de novo in patients
      without breast implants have been reported. We report a case of a 19-year-old
      female who presented with a lump in the right breast of 3 months' duration.
      Examination revealed an Eastern Cooperative Oncology Group performance status of
      2 and a 6.5 cm2 lump in the right breast. Lumpectomy revealed large neoplastic
      cells positive for CD30, EMA, CD5, and anaplastic lymphoma kinase (ALK),
      suggestive of anaplastic large cell lymphoma. The patient underwent lumpectomy
      followed by 6 cycles of anthracycline-based chemotherapy with cyclophosphamide,
      doxorubicin, vincristine, and prednisolone 3 weekly. On follow up, this patient
      had an event-free survival of 23 months. We are reporting this case of ALCL (ALK
      positive) in a patient with no breast implant previously, and hence, it is of
      clinical importance. 

PMID- 25971834
TI  - Rectal impaction by pomegranate seeds.

PMID- 25971835
TI  - Kounis syndrome and antibiotics.

PMID- 25971836
TI  - Lessons learned from recruiting socioeconomically disadvantaged smokers into a
      pilot randomized controlled trial to explore the role of Exercise Assisted
      Reduction then Stop (EARS) smoking.
AB  - BACKGROUND: Research is needed on what influences recruitment to smoking
      reduction trials, and how to increase their reach. The present study aimed to i)
      assess the feasibility of recruiting a disadvantaged population, ii) examine the
      effects of recruitment methods on participant characteristics, iii) identify
      resource requirements for different recruitment methods, and iv) to qualitatively
      assess the acceptability of recruitment. This was done as part of a pilot two-arm
      trial of the effectiveness of a novel behavioral support intervention focused on
      increasing physical activity and reducing smoking, among disadvantaged smokers
      not wishing to quit. METHODS: Smokers were recruited through mailed invitations
      from three primary care practices (62 participants) and one National Health Stop
      Smoking Service (SSS) database (31 participants). Six other participants were
      recruited via a variety of other community-based approaches. Data were collected
      through questionnaires, field notes, work sampling, and databases. Chi-squared
      and t-tests were used to compare baseline characteristics of participants.
      RESULTS: We randomized between 5.1 and 11.1% of those invited through primary
      care and SSS, with associated researcher time to recruit one participant varying
      from 18 to 157 minutes depending on time and intensity invested.Only six
      participants were recruited through a wide variety of other community-based
      approaches, with an associated researcher time of 469 minutes to recruit one
      participant. Targets for recruiting a disadvantaged population were met, with 91%
      of the sample in social classes C2 to E (NRS social grades, UK), and 41%
      indicating mental health problems. Those recruited from SSS were more likely to
      respond to an initial letter, had used cessation aids before, and had attempted
      to quit in the past year. Overall, initial responders were more likely to be
      physically active than those who were recruited via follow-up telephone calls. No
      other demographics or behaviour characteristics were associated with recruitment
      approach or intensity of effort. Qualitative feedback indicated that participants
      had been attracted by the prospect of support that focused on smoking reduction
      rather than abrupt quitting. CONCLUSIONS: Mailed invitations, and follow-up, from
      health professionals was an effective method of recruiting disadvantaged smokers
      into a trial of an exercise intervention to aid smoking reduction. Recruitment
      via community outreach approaches was largely ineffective. TRIAL REGISTRATION:
      ISRCTN identifier: 13837944 , registered on 6 July 2010.

PMID- 25971837
TI  - Radioactive (125)I seeds inhibit cell growth and epithelial-mesenchymal
      transition in human glioblastoma multiforme via a ROS-mediated signaling pathway.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary central
      nervous system neoplasm in adults. Radioactive (125)I seed implantation has been
      widely applied in the treatment of cancers. Moreover, previous clinical trials
      have confirmed that (125)I seeds treatment was an effective therapy in GBM. We
      sought to investigate the effect of (125)I seed on GBM cell growth and Epithelial
      mesenchymal transition (EMT). METHODS: Cells were exposed to irradiation at
      different doses. Colony-formation assay, EdU assay, cell cycle analysis, and
      TUNEL assay were preformed to investigate the radiation sensitivity. The effects
      of (125)I seeds irradiation on EMT were measured by transwell, Boyden and wound
      healing assays. The levels of reactive oxygen species (ROS) were measured by DCF
      DA assay. Moreover, the radiation sensitivity and EMT were investigated with or
      without pretreatment with glutathione. Additionally, nude mice with tumors were
      measured after treated with radiation. RESULTS: Radioactive (125)I seeds are more
      effective than X-ray irradiation in inhibiting GBM cell growth. Moreover, EMT was
      effectively inhibited by (125)I seed irradiation. A mechanism study indicated
      that GBM cell growth and EMT inhibition were induced by (125)I seeds with the
      involvement of a ROS-mediated signaling pathway. CONCLUSIONS: Radioactive (125)I
      seeds exhibit novel anticancer activity via a ROS-mediated signaling pathway.
      These findings have clinical implications for the treatment of patients with GBM
      by (125)I seeds.

PMID- 25971838
TI  - Taxonomy of the burden of treatment: a multi-country web-based qualitative study
      of patients with chronic conditions.
AB  - BACKGROUND: Management strategies for patients with chronic conditions are
      becoming increasingly complex, which may result in a burden of treatment for
      patients. To develop a Minimally Disruptive Medicine designed to reduce the
      burden of treatment, clinicians need to understand which healthcare tasks and
      aggravating factors may be responsible for this burden. The objective of the
      present study was to describe and classify the components of the burden of
      treatment for patients with chronic conditions from the patient's perspective.
      METHODS: We performed a multi-country qualitative study using an online survey
      and a purposive sampling strategy to select English-, French-, and Spanish
      speaking participants with different chronic conditions. Participants were
      recruited by physicians, patients' associations, advertisement on social media,
      and 'snowballing'. The answers were analyzed by i) manual content analysis with a
      grounded theory approach, coded by two researchers, and ii) automatic textual
      analysis by Reinert's method. RESULTS: Between 2013 and 2014, 1,053 participants
      from 34 different countries completed the online survey using 408,625 words.
      Results from both analyses were synthesized in a taxonomy of the burden of
      treatment, which described i) the tasks imposed on patients by their diseases and
      by their healthcare system (e.g., medication management, lifestyle changes,
      follow-up, etc.); ii) the structural (e.g., access to healthcare resources,
      coordination between care providers), personal, situational, and financial
      factors that aggravated the burden of treatment; and iii) patient-reported
      consequences of the burden (e.g., poor adherence to treatments, financial burden,
      impact on professional, family, and social life, etc.). Our findings may not be
      applicable to patients with chronic conditions who differ from those who
      responded to our survey. CONCLUSIONS: Our taxonomy of the burden of treatment,
      provided by patients with chronic conditions from different countries and
      settings, supports the development of tools to ascertain the burden of treatment
      and highlights potential targets for interventions to minimize it.

PMID- 25971839
TI  - In vitro catalytic activity of N-terminal and C-terminal domains in NukM, the
      post-translational modification enzyme of nukacin ISK-1.
AB  - Lantibiotics are antibacterial peptides containing unique thioether cross-links
      termed lanthionine and methyllanthionine. NukM, the modifying enzyme of nukacin
      ISK-1, which is produced by Staphylococcus warneri ISK-1, catalyzes the
      dehydration of specific Ser/Thr residues in a precursor peptide, followed by
      conjugative addition of intramolecular Cys to dehydrated residues to generate a
      cyclic structure. By contrast, the precursor peptide of nisin is modified by 2
      enzymes, NisB and NisC, which mediate dehydration and cyclization, respectively.
      While the C-terminal domain of NukM is homologous to NisC, the N-terminal domain
      has no homology with other known proteins. We expressed and characterized the N-
      and C-terminal domains of NukM, NukMN, and NukMC, separately. In vitro
      reconstitution revealed that full-length NukM fully modified the substrate
      peptide NukA. NukMN partially phosphorylated, dehydrated, and cyclized NukA. By
      contrast, NukMC did not catalyze dehydration, phosphorylation, or cyclization
      reactions. Interaction studies using surface plasmon resonance analysis indicated
      that NukM and NukMN can bind NukA with high affinity, whereas NukMC has low
      substrate-recognition activity. These results suggest that NukMN is mainly
      responsible for substrate recognition and dehydration and that the whole NukM
      structure, including the C-terminal domain, is required for the complete
      modification of NukA. To the best of our knowledge, this is the first report
      providing insights into the in vitro catalytic activity of individual domains of
      a LanM-type modification enzyme.

PMID- 25971840
TI  - Plasma clot properties in patients with a mild-to-moderate bleeding tendency of
      unknown cause.
AB  - In a large proportion of patients with mild bleeding disorders (MBDs) no
      diagnosis can be established by routine coagulation tests. We investigated
      whether alterations in plasma clot properties account for MBDs of unknown cause.
      Ninety-five patients with MBDs of unknown origin and 98 age- and sex-matched
      healthy controls were investigated. Furthermore, data of 25 patients with a
      deficiency of factor VIII were analyzed. Plasma clot characteristics in the
      absence and presence of recombinant tissue plasminogen activator (rtPA)
      represented by the lag phase, rate of protofibril formation (Vmax), fibrin
      structure (DeltaAbs), time to peak (TTP), half lysis time (t50 and area under the
      curve (AUC) were measured in turbidometric clot formation and lysis assays. In
      the fibrinolysis assay, Vmax was lower in patients than in healthy controls. No
      differences in the other parameters of clot formation and lysis were detected
      between the groups. There was no clear association of plasma clot properties with
      the clinical severity of bleeding in patients with MBDs. Patients with known
      decreased factor VIII levels also showed a lower Vmax. Fibrinogen levels were
      positively associated with each of the assessed parameters in both groups, with
      the strongest association with DeltaAbs, indicating altered fibrin structure.
      Factor VIII activity correlated with altered clot characteristics similar to
      fibrinogen, especially in patients, with the strongest positive correlation to
      Vmax. This cohort of patients with MBDs of unknown origin showed a lower rate of
      fibrin formation in the fibrinolysis assay, but otherwise similar plasma clot
      properties compared to healthy controls. 

PMID- 25971841
TI  - Evaluation of the influence of cardiac motion on the accuracy and reproducibility
      of longitudinal measurements and the corresponding image quality in optical
      frequency domain imaging: an ex vivo investigation of the optimal pullback speed.
AB  - Longitudinal measurement using intravascular ultrasound is limited because the
      motorized pullback device assumes no cardiac motion. A newly developed
      intracoronary imaging modality, optical frequency domain imaging (OFDI), has
      higher resolution and an increased auto-pullback speed with presumably lesser
      susceptibility to cardiac motion artifacts during pullback for longitudinal
      measurement; however, it has not been fully investigated. We aimed to clarify the
      influence of cardiac motion on the accuracy and reproducibility of longitudinal
      measurements obtained using OFDI and to determine the optimal pullback speed.
      This ex vivo study included 31 stents deployed in the mid left anterior
      descending artery under phantom heartbeat and coronary flow simulation.
      Longitudinal stent lengths were measured twice using OFDI at three pullback
      speeds. Differences in stent lengths between OFDI and microscopy and between two
      repetitive pullbacks were assessed to determine accuracy and reproducibility.
      Furthermore, three-dimensional (3D) reconstruction was used for evaluating image
      quality. With regard to differences in stent length between OFDI and microscopy,
      the intraclass correlation coefficient values were 0.985, 0.994, and 0.995 at 10,
      20, and 40 mm/s, respectively. With regard to reproducibility, the values were
      0.995, 0.996, and 0.996 at 10, 20, and 40 mm/s, respectively. 3D reconstruction
      showed a superior image quality at 10 and 20 mm/s compared with that at 40 mm/s.
      OFDI demonstrated high accuracy and reproducibility for longitudinal stent
      measurements. Moreover, its accuracy and reproducibility were remarkable at a
      higher pullback speed. A 20-mm/s pullback speed may be optimal for clinical and
      research purposes.

PMID- 25971843
TI  - An Investigation of the Molecular Mechanism of Double cMyBP-C Mutation in a
      Patient with End-Stage Hypertrophic Cardiomyopathy.
AB  - Mutations in the gene coding for cardiac myosin binding protein-C (cMyBP-C), a
      multi-domain (C0-C10) protein, are a major causative factor for inherited
      hypertrophic cardiomyopathy. Patients carrying mutations in this gene have an
      extremely heterogeneous clinical course, with some progressing to end-stage heart
      failure. The cause of this variability is unknown. We here describe molecular
      modeling of a double mutation in domains C1 (E258K) and C2 (E441K) in a patient
      with severe HCM phenotype. The three-dimensional structure for the C1-motif-C2
      complex was constructed with double and single mutations being introduced.
      Molecular dynamic simulations were performed for 10 ns under physiological
      conditions. The results showed that both E258K and E441K in isolation can
      predominantly affect the native domain as well as the nearby motif via
      conformational changes and result in an additive effect when they coexist. These
      changes involve important regions of the motif such as phosphorylation and
      potential actin-binding sites. Moreover, the charge reversal mutations altered
      the surface electrostatic properties of the complex. In addition, we studied
      protein expression, which showed that the mutant proteins were expressed and we
      can suppose that the severe phenotype was not due to haploinsufficiency. However,
      additional studies on human gene expression will need to confirm this hypothesis.
      The double mutation affecting the regulatory N-terminal of cMyBP-C have the
      potential of synergistically interfering with the binding to neighbouring domains
      and other sarcomeric proteins. These effects may account for the severe phenotype
      and clinical course observed in the complex cMyBP-C genotypes.

PMID- 25971842
TI  - Inhibition of vemurafenib-resistant melanoma by interference with pre-mRNA
      splicing.
AB  - Mutations in the serine/threonine kinase BRAF are found in more than 60% of
      melanomas. The most prevalent melanoma mutation is BRAF(V600E), which
      constitutively activates downstream MAPK signalling. Vemurafenib is a potent RAF
      kinase inhibitor with remarkable clinical activity in BRAF(V600E)-positive
      melanoma tumours. However, patients rapidly develop resistance to vemurafenib
      treatment. One resistance mechanism is the emergence of BRAF alternative splicing
      isoforms leading to elimination of the RAS-binding domain. Here we identify
      interference with pre-mRNA splicing as a mechanism to combat vemurafenib
      resistance. We find that small-molecule pre-mRNA splicing modulators reduce BRAF3
      9 production and limit in-vitro cell growth of vemurafenib-resistant cells. In
      xenograft models, interference with pre-mRNA splicing prevents tumour formation
      and slows growth of vemurafenib-resistant tumours. Our results identify an
      intronic mutation as the molecular basis for a RNA splicing-mediated RAF
      inhibitor resistance mechanism and we identify pre-mRNA splicing interference as
      a potential therapeutic strategy for drug resistance in BRAF melanoma. 

PMID- 25971845
TI  - Association between obesity and glomerular hyperfiltration: the confounding
      effect of smoking and sodium and protein intakes.
AB  - PURPOSE: Glomerular hyperfiltration has been suggested as a possible mechanism
      linking obesity and chronic kidney disease (CKD), independently of classical risk
      factors. We explored the association of overweight and obesity with glomerular
      hyperfiltration in a large sample of the Swiss adult population, accounting for
      several confounders including dietary factors. METHODS: Data from a 2010 to 2012
      cross-sectional population-based survey in Switzerland were used. Creatinine
      clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was
      used to define glomerular hyperfiltration. Participants were categorized into
      lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (>=30 kg/m(2))
      according to body mass index (BMI). RESULTS: A total of 1339 participants were
      included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men].
      The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively.
      Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and
      124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of
      glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7
      %, respectively; p < 0.001). This positive association remained significant after
      adjusting for age, sex, hypertension, diabetes, smoking and dietary factors
      (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001)
      for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus
      lean. CONCLUSIONS: BMI categories and glomerular hyperfiltration are positively
      associated, independently of other known CKD risk factors and dietary
      confounders, suggesting that glomerular hyperfiltration may represent an early
      renal phenotype in obesity. Our observations confirm the significant association
      of glomerular hyperfiltration with sodium and protein intakes and identify sodium
      intake as an important modifying factor of the association between
      hyperfiltration and obesity.

PMID- 25971847
TI  - Minimum cement volume required in vertebral body augmentation--A biomechanical
      study comparing the permanent SpineJack device and balloon kyphoplasty in
      traumatic fracture.
AB  - BACKGROUND: Minimally invasive treatment of vertebral fractures is basically
      characterized by cement augmentation. Using the combination of a permanent
      implant plus cement, it is now conceivable that the amount of cement can be
      reduced and so this augmentation could be an attractive opportunity for use in
      traumatic fractures in young and middle-aged patients. The objective of this
      study was to determine the smallest volume of cement necessary to stabilize
      fractured vertebrae comparing the SpineJack system to the gold standard, balloon
      kyphoplasty. METHODS: 36 fresh frozen human cadaveric vertebral bodies (T11-L3)
      were utilized. After creating typical compression wedge fractures (AO A1.2.1),
      the vertebral bodies were reduced by SpineJack (n=18) or kyphoplasty (n=18) under
      preload (100N). Subsequently, different amounts of bone cement (10%, 16% or 30%
      of the vertebral body volume) were inserted. Finally, static and dynamic
      biomechanical tests were performed. FINDINGS: Following augmentation and fatigue
      tests, vertebrae treated with SpineJack did not show any significant loss of
      intraoperative height gain, in contrast to kyphoplasty. In the 10% and 16%-group
      the height restoration expressed as a percentage of the initial height was
      significantly increased with the SpineJack (>300%). Intraoperative SpineJack
      could preserve the maximum height gain (mean 1% height loss) better than
      kyphoplasty (mean 16% height loss). INTERPRETATION: In traumatic wedge fractures
      it is possible to reduce the amount of cement to 10% of the vertebral body volume
      when SpineJack is used without compromising the reposition height after
      reduction, in contrast to kyphoplasty that needs a 30% cement volume.

PMID- 25971848
TI  - Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular
      risk in hemodialysis patients.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
      mortality in hemodialysis patients; the increased risk of cardiovascular disease
      is due to accelerated atherosclerosis, inflammation and impaired lipoprotein
      metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp
      PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed
      patients in order to evaluate the relationship with the accelerated
      atherosclerosis and vascular accidents. METHODS: In 102 dialysis patients and 40
      non-uremic controls, we investigated the lipoprotein plasma profile, high
      sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein
      (SAA), and followed patients for 1 year to analyze the risk of acute
      cardiovascular events. RESULTS: Total cholesterol, low-density lipoprotein and
      high-density lipoprotein plasma levels were significantly lower in uremic
      patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio
      with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels
      >194 nmol/min/ml had more acute cardiovascular events than patients with lower
      values. CONCLUSION: Our results show that in dialysis subjects: (1) low-density
      lipoproteins show a more atherogenic phenotype than in the general population;
      (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could
      potentially be used to evaluate cardiovascular risk.

PMID- 25971846
TI  - Imaging PEG-like nanoprobes in tumor, transient ischemia, and inflammatory
      disease models.
AB  - The iron chelator deferoxamine (DFO), approved for the treatment of iron
      overload, has been examined as a therapeutic in a variety of conditions which
      iron may exacerbate. To evaluate the potential of DFO-bearing PEG-like nanoprobes
      (DFO-PNs) as therapeutics, we determined their pharmacokinetics (PK) in normal
      mice, and imaged their accumulation in a tumor model and in models of transient
      brain ischemia and inflammation. DFO-PNs consist of a DFO, a Cy5.5, and PEG (5
      kDa or 30 kDa) attached to Lys-Cys scaffold. Tumor uptake of a [(89)Zr]:DFO
      PN(10) (30 kDa PEG, diameter 10 nm) was imaged by PET, surface fluorescence, and
      fluorescence microscopy. DFO-PN(10) was internalized by tumor cells (fluorescence
      microscopy) and by cultured cells (by FACS). [(89)Zr]:DFO-PN(4.3) (5 kDa PEG,
      diameter 4.3 nm) concentrated at incision generated inflammations but not at
      sites of transient brain ischemia. DFO-PNs are fluorescent, PK tunable forms of
      DFO that might be investigated as antitumor or anti-inflammatory agents. 

PMID- 25971844
TI  - Mechanotransduction Mechanisms for Intraventricular Diastolic Vortex Forces and
      Myocardial Deformations: Part 2.
AB  - Epigenetic mechanisms are fundamental in cardiac adaptations, remodeling, reverse
      remodeling, and disease. A primary goal of translational cardiovascular research
      is recognizing whether disease-related changes in phenotype can be averted by
      eliminating or reducing the effects of environmental epigenetic risks. There may
      be significant medical benefits in using gene-by-environment interaction
      knowledge to prevent or reverse organ abnormalities and disease. This survey
      proposes that "environmental" forces associated with diastolic RV/LV rotatory
      flows exert important, albeit still unappreciated, epigenetic actions influencing
      functional and morphological cardiac adaptations. Mechanisms analogous to
      Murray's law of hydrodynamic shear-induced endothelial cell modulation of
      vascular geometry are likely to link diastolic vortex-associated shear, torque
      and "squeeze" forces to RV/LV adaptations. The time has come to explore a new
      paradigm in which such forces play a fundamental epigenetic role, and to work out
      how heart cells react to them. Findings from various imaging modalities,
      computational fluid dynamics, molecular cell biology and cytomechanics are
      considered. The following are examined, among others: structural dynamics of
      myocardial cells (endocardium, cardiomyocytes, and fibroblasts), cytoskeleton,
      nucleoskeleton, and extracellular matrix; mechanotransduction and signaling; and
      mechanical epigenetic influences on genetic expression. To help integrate and
      focus relevant pluridisciplinary research, rotatory RV/LV filling flow is placed
      within a working context that has a cytomechanics perspective. This new frontier
      in cardiac research should uncover versatile mechanistic insights linking filling
      vortex patterns and attendant forces to variable expressions of gene regulation
      in RV/LV myocardium. In due course, it should reveal intrinsic homeostatic
      arrangements that support ventricular myocardial function and adaptability. 

PMID- 25971849
TI  - Serum biomarkers in uncontrolled no heart-beating donors may identify kidneys
      that will never work after transplantation.
AB  - BACKGROUND/AIMS: Kidneys from uncontrolled non heart-beating donors achieve a
      good level of renal function after transplantation. However, a number of them
      will never function in the recipient. Our aim was to determine if serum
      biomarkers associated with platelet activity, inflammation and the nitric oxide
      system in uncontrolled non heart-beating donors may help to predict no renal
      function recovery after renal transplantation. METHODS: Serum levels of
      interleukin (IL)-6, IL-10, intercellular cell adhesion molecule-1 (ICAM-1),
      cyclic guanosine monophosphate (cGMP), nitrite + nitrate and platelet factor-4
      (PF4) were measured using enzyme-linked immunosorbent assay (ELISA) kits in 88
      uncontrolled non heart-beating donors divided according to the renal
      functionality achieved in the recipients into functional (n = 76) and non
      functional (n = 12). RESULTS: Kidneys from donors with higher IL-6 levels (>900
      pg/ml) were functional after transplantation. Serum cGMP levels below 372.3
      fmol/l were also associated with kidneys that recovered the renal function.
      However, serum levels of PF4 showed the best correlation with recovery of renal
      functional in the recipients since they were significantly lower in the donors
      whose kidneys functioned after transplantation. CONCLUSIONS: Serum PF4 levels in
      uncontrolled non heart-beating donors may be a good predictor for kidneys that
      never will reach functional recovery. Some serum cGMP, IL-6 and IL-10 levels may
      simply help identify kidneys that will function after transplantation.

PMID- 25971851
TI  - Adaption of pregnancy anxiety questionnaire-revised for all pregnant women
      regardless of parity: PRAQ-R2.
AB  - The 10-item Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R) is a widely
      used instrument to assess and identify pregnancy-specific anxiety in nulliparous
      women. It has good psychometric values and predictive validity for birth and
      childhood outcomes. Nonetheless, the PRAQ-R is not designed for use in parous
      women, as particularly one item of the questionnaire is not relevant for women
      who gave birth before. We tested the factorial and scalar invariance of a
      modified PRAQ-R2 across nulliparous and parous women with an adapted item to fit
      both groups of pregnant women. A longitudinal study among 1144 pregnant women (n
      = 608 nulliparous and n = 536 parous) with two repeated measures of the PRAQ-R2
      was used to test for measurement invariance of the instrument. Results show
      metric and scalar invariance, indicating that the PRAQ-R2 measures similar
      constructs on the same scale for all pregnant women at two different times during
      pregnancy. We conclude that the PRAQ-R2 can be used, compared, or combined in a
      sample of nulliparous and parous women.

PMID- 25971850
TI  - Role of tubulointerstitial plasmin in the progression of IgA nephropathy.
AB  - BACKGROUND: Plasmin has recently been reported to be associated with renal
      fibrosis in experimental models, but its role in human renal diseases is unclear.
      METHODS: Fifty-seven patients with IgA nephropathy (IgAN) were evaluated
      retrospectively. Plasmin in their renal biopsy tissues was assessed by in situ
      zymography using a plasmin-sensitive synthetic peptide, and the relationships
      between patients' histologic or clinical parameters and their renal plasmin
      activity [assessed semiquantitatively by calculating the positively stained
      percentage of the total tubulointerstitial (TI) area] were evaluated. RESULTS:
      Plasmin activity was observed almost exclusively in the TI space (mainly in the
      interstitium and partly in the tubular epithelial cells) and was significantly
      stronger in patients with TI lesion (tubular atrophy/interstitial fibrosis and
      tubulointerstitial inflammation) than in those without TI lesion. It was
      significantly and positively correlated with the global glomerulosclerosis rate
      and significantly and negatively correlated with estimated glomerular filtration
      rate not only at the time of renal biopsy but also at the end of the follow-up
      period. Double stainings for plasmin activity and inflammatory cells,
      cytokeratin, or alpha-smooth muscle actin (alpha-SMA) in selected patients
      revealed TI infiltration of inflammatory cells, attenuated tubular epithelial
      expression of cytokeratin, and augmented interstitial expression of alpha-SMA
      close to upregulated plasmin activity in the TI space. CONCLUSIONS: These data
      suggest that TI plasmin is associated with TI inflammation leading to renal
      fibrosis, and can cause the decline in renal function seen in patients with IgAN.
      Reducing plasmin in situ may therefore be a promising therapeutic approach
      slowing renal fibrogenesis and improving renal function.

PMID- 25971852
TI  - Prevalence and risk factors for cannabis use in low-income pregnant women in Sao
      Paulo, Brazil.
AB  - Cannabis is the most commonly used illicit drug during the perinatal period and
      has potential risks to the fetus. The purpose of this study is to estimate the 1
      year prevalence of cannabis use and identify associated factors for a population
      of low-income pregnant women in Brazil. We performed a cross-sectional analysis
      of 831 women surveyed using a structured questionnaire to collect
      sociodemographic, clinical, and substance use history. The 1-year prevalence of
      antenatal cannabis use was 4.2 %; reported lifetime use was 9.6 %. The presence
      of a common mental disorder and active tobacco smoking were independently
      associated with cannabis use, OR = 3.3 (95 % CI 1.65-6.59) and OR = 6.89 (95 % CI
      3.45-13.8), respectively.

PMID- 25971854
TI  - Recurrent ischial pressure ulcer resolved with a novel tissue adhesive: a case
      report.
AB  - INTRODUCTION: Patients with stage III and IV pressure ulcers requiring surgical
      reconstruction remain a challenge. Extended hospitalization, and high costs of
      care per patient episode due to high rates of complications and recurrence, make
      efforts to reduce these rates of utmost importance to the medical community in
      general. We report a case in which two prior attempts at surgical resolution had
      failed, and which was successfully resolved with the aid of a new tissue adhesive
      designed for the closure of dead space. To the best of our knowledge, this is the
      first reported example of the use of this adhesive in flap surgery for pressure
      ulcers. CASE PRESENTATION: We report the case of a 42-year-old Caucasian
      wheelchair-bound paraplegic man with history of spina bifida, urinary catheter,
      colostomy, and a history of pressure ulcers. He presented to our institution with
      a stage IV, methicillin-resistant Staphylococcus aureus-contaminated pressure
      sore on his left ischial tuberosity. A first procedure using V-Y and rotational
      flap closure dehisced on postoperative day three due to his excessive movement. A
      second procedure was performed but this also required revision due to dehiscence
      related to fluid accumulation under the flap. A third procedure using
      TissuGlu((r)) Surgical Adhesive to adhere the flap and close the dead space
      resulted in successful resolution. At his last follow-up appointment at seven
      weeks post-operation he was healing well and was back in his wheelchair.
      CONCLUSIONS: Any reductions in hospital stay, complication rates, or recurrence
      rates would be important in this highly problematic group of patients.
      Elimination of the dead space where fluids can accumulate, combined with adhesion
      of the flaps with a sufficient strength to withstand the shear forces commonly
      encountered, could represent an important advancement in the treatment of
      pressure ulcers requiring surgical repair with myocutaneous or fasciocutaneous
      flaps. Our initial experience in this case suggests that TissuGlu((r)) may be
      able to help reduce recurrence rates in this challenging group of patients.

PMID- 25971853
TI  - Test-retest reliability of retrospective self-reported maternal exposure to
      childhood abuse and neglect.
AB  - Retrospective reports of exposure to childhood trauma indicate it is common.
      There is growing interest in relationships between maternal exposure to childhood
      adversity, perinatal mental health, and pregnancy outcomes. The goal of this
      study was to describe the self-reported prevalence and test-retest reliability of
      exposure to childhood maltreatment using the Childhood Trauma Questionnaire among
      adult women around the time of pregnancy. A substantial proportion of women
      reported exposure to maltreatment and reliability was generally at least
      moderate, indicating consistent reporting. 

PMID- 25971855
TI  - Preparation of upper critical solution temperature (UCST) responsive diblock
      copolymers bearing pendant ureido groups and their micelle formation behavior in
      water.
AB  - Poly(2-ureidoethyl methacrylate) (PUEM) was prepared via reversible addition
      fragmentation chain transfer (RAFT) controlled radical polymerization and a post
      modification reaction. PUEM shows upper critical solution temperature (UCST)
      behavior in aqueous solution. Although PUEM can dissolve in water above the UCST,
      it cannot dissolve in water below the UCST. Diblock copolymers (MmUn) composed of
      a biocompatible hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)
      block and a PUEM block with different compositions were prepared via RAFT radical
      polymerization and a post-modification reaction. "M" and "U" represent PMPC and
      PUEM blocks, respectively, and the subscripts represent the degree of
      polymerization of each block. M95U149 and M20U163 formed polymer micelles
      comprising a PUEM core and a PMPC shell below the critical aggregation
      temperature (Tc) in aqueous solution. Polymer micelles were formed from M20U163
      below 32  degrees C, which can incorporate guest molecules into the core. 

PMID- 25971856
TI  - Tramadol for the management of premature ejaculation: a timely systematic review.
AB  - Premature ejaculation (PE) represents a common sexual dysfunction and is
      associated with a negative impact on quality of life and relationships. Recent
      evidence suggests that on-demand dosing of tramadol is effective at increasing
      intra-vaginal ejaculatory latency time (IELT) and improving subjective measures
      of satisfaction. A literature review was performed of journal articles published
      between January 2000 and July 2014 that matched the keywords 'tramadol' and
      'premature ejaculation'. We identified eight relevant articles with the criteria
      that each article be published in a peer-reviewed journal, represent original
      work and be written in English. IELT was used as the primary outcome in each of
      the papers reviewed for efficacy. Additional subjective outcome measures were
      reviewed where available. Safety was assessed using adverse event data from the
      individual studies. We found that tramadol in on-demand dosing is effective at
      lengthening IELT in men with varying degrees of PE and improves patient
      satisfaction. Tramadol was generally well tolerated, particularly among those
      taking 25 and 50 mg doses. Although there is a risk of abuse and dependence,
      these events are rare, particularly at low doses taken intermittently. In
      conclusion, tramadol is an effective oral therapy for PE that is overall safe and
      well tolerated. 

PMID- 25971858
TI  - Concordance of sexual dysfunction and dissatisfaction by self-report and those by
      partner's perception in young adult couples.
AB  - We evaluated concordance levels of young adult spouses (N=107 couples, total
      N=214) with regards to sexual satisfaction by using Golombock-Rust Inventory of
      Sexual Satisfaction (GRISS). Each spouse of the couples filled out both female
      and male forms of the GRISS. Self- and spouse-reported scores were analyzed in
      terms of inter-rater correlation and agreement. The prevalence of overall sexual
      dissatisfaction was 10.3% and 26.2% in wives and husbands, respectively. The
      correlation coefficient (r) between the self-reported overall sexual satisfaction
      scores and those assessed by the spouses was 0.25 (P=0.014) and 0.04 (P=0.680)
      for wives and husbands, respectively. The sensitivity for perception of partner's
      sexual problems ranged 11% to 47%, and the specificity was around 64% to 100%,
      except for vaginismus, which had a sensitivity of 83% and a specificity of 25%.
      The prevalance-adjusted and bias-adjusted kappa (PABAK) value for overall sexual
      dissatisfaction reported by themselves and that assessed by their spouses was
      0.68 and 0.16 for the wives and husbands, respectively. For specific female
      sexual problems, the PABAK value was the highest in female dissatisfaction (0.81)
      followed by anorgasmia (0.78), female avoidance (0.44), vaginismus (0.44),
      infrequency (0.33), non-communication (0.14) and female nonsensuality (0.14). For
      specific male sexual problems, the PABAK value was the highest in male
      nonsensuality (1.00), followed by male dissatisfaction (0.78), infrequency
      (0.46), non-communication (0.42), male avoidance (0.36), impotence (0.27) and
      premature ejaculation (-0.04). Our findings suggested that in this clinical
      sample the partner's perception of sexual dysfunction and dissatisfaction did not
      correlate well with the subject's self-reported sexual problems, and generally
      male sexual problems were less correctly perceived by the partners than were
      female sexual problems. This result may provide helpful information for
      clinicians who take care of patients' sexual problems. 

PMID- 25971857
TI  - Sex differences in interactions between nucleus accumbens and visual cortex by
      explicit visual erotic stimuli: an fMRI study.
AB  - Men tend to have greater positive responses than women to explicit visual erotic
      stimuli (EVES). However, it remains unclear, which brain network makes men more
      sensitive to EVES and which factors contribute to the brain network activity. In
      this study, we aimed to assess the effect of sex difference on brain connectivity
      patterns by EVES. We also investigated the association of testosterone with brain
      connection that showed the effects of sex difference. During functional magnetic
      resonance imaging scans, 14 males and 14 females were asked to see alternating
      blocks of pictures that were either erotic or non-erotic. Psychophysiological
      interaction analysis was performed to investigate the functional connectivity of
      the nucleus accumbens (NA) as it related to EVES. Men showed significantly
      greater EVES-specific functional connection between the right NA and the right
      lateral occipital cortex (LOC). In addition, the right NA and the right LOC
      network activity was positively correlated with the plasma testosterone level in
      men. Our results suggest that the reason men are sensitive to EVES is the
      increased interaction in the visual reward networks, which is modulated by their
      plasma testosterone level. 

PMID- 25971859
TI  - Current status of revascularization surgery for Moyamoya disease: special
      consideration for its 'internal carotid-external carotid (IC-EC) conversion' as
      the physiological reorganization system.
AB  - Moyamoya disease is a chronic cerebrovascular disease with unknown etiology,
      which is characterized by bilateral steno-occlusive changes at the terminal
      portion of the internal carotid artery and an abnormal vascular network formation
      at the base of the brain. Moyamoya disease is known to have unique and dynamic
      nature to convert the vascular supply for the brain from internal carotid (IC)
      system to the external carotid (EC) system, as indicated by Suzuki's angiographic
      staging established in 1969. Insufficiency of this 'IC-EC conversion system' may
      result in cerebral ischemia, as well as in intracranial hemorrhage from
      inadequate collateral vascular network, both of which represent the clinical
      presentation of moyamoya disease. Therefore, surgical revascularization by
      extracranial-intracranial bypass is the preferred procedure for moyamoya disease
      to complement 'IC-EC conversion' and thus to avoid cerebral infarction and/or
      intracranial hemorrhage. Long-term outcome of revascularization surgery for
      moyamoya disease is favorable, but rapid increase in cerebral blood flow on the
      affected hemisphere could temporarily cause unfavorable phenomenon such as
      cerebral hyperperfusion syndrome. We would review the current status of
      revascularization surgery for moyamoya disease based on its basic pathology, and
      sought to discuss the significance of measuring cerebral blood flow in the acute
      stage and intensive perioperative management. 

PMID- 25971860
TI  - Development of fluorescent probes based on protection-deprotection of the key
      functional groups for biological imaging.
AB  - Recently, the strategy of protection-deprotection of functional groups has been
      widely employed to design fluorescent probes, as the protection-deprotection of
      functional groups often induces a marked change in electronic properties.
      Significant advances have been made in the development of analyte-responsive
      fluorescent probes based on the protection-deprotection strategy. In this
      tutorial review, we highlight the representative examples of small-molecule based
      fluorescent probes for bioimaging, which are operated via the protection
      deprotection of key functional groups such as aldehyde, hydroxyl, and amino
      functional groups reported from 2010 to 2014. The discussion includes the general
      protection-deprotection methods for aldehyde, hydroxyl, or amino groups, as well
      as the design strategies, sensing mechanisms, and deprotection modes of the
      representative fluorescent imaging probes applied to bio-imaging. 

PMID- 25971861
TI  - Genome-wide analysis of AP2/ERF transcription factors in carrot (Daucus carota
      L.) reveals evolution and expression profiles under abiotic stress.
AB  - AP2/ERF is a large transcription factor family that regulates plant physiological
      processes, such as plant development and stress response. Carrot (Daucus carota
      L.) is an important economical crop with a genome size of 480 Mb; the draft
      genome sequencing of this crop has been completed by our group. However, little
      is known about the AP2/ERF factors in carrot. In this study, a total of 267
      putative AP2/ERF factors were identified from the whole-genome sequence of
      carrot. These AP2/ERF proteins were phylogenetically clustered into five
      subfamilies based on their similarity to the amino acid sequences from
      Arabidopsis. The distribution and comparative genome analysis of the AP2/ERF
      factors among plants showed the AP2/ERF factors had expansion during the
      evolutionary process, and the AP2 domain was highly conserved during evolution.
      The number of AP2/ERF factors in land plants expanded during their evolution. A
      total of 60 orthologous and 145 coorthologous AP2/ERF gene pairs between carrot
      and Arabidopsis were identified, and the interaction network of orthologous genes
      was constructed. The expression patterns of eight AP2/ERF family genes from each
      subfamily (DREB, ERF, AP2, and RAV) were related to abiotic stresses. Yeast one
      hybrid and beta-galactosidase activity assays confirmed the DRE and GCC box
      binding activities of DREB subfamily genes. This study is the first to identify
      and characterize the AP2/ERF transcription factors in carrot using whole-genome
      analysis, and the findings may serve as references for future functional research
      on the transcription factors in carrot. 

PMID- 25971863
TI  - Breath analysis: translation into clinical practice.
AB  - Breath analysis in respiratory disease is a non-invasive technique which has the
      potential to complement or replace current screening and diagnostic techniques
      without inconvenience or harm to the patient. Recent advances in ion mobility
      spectrometry (IMS) have allowed exhaled breath to be analysed rapidly, reliably
      and robustly thereby facilitating larger studies of exhaled breath profiles in
      clinical environments. Preliminary studies have demonstrated that volatile
      organic compound (VOC) breath profiles of people with respiratory disease can be
      distinguished from healthy control groups but there is a need to validate,
      standardise and ensure comparability between laboratories before real-time breath
      analysis becomes a clinical reality. It is also important that breath sampling
      procedures and methodologies are developed in conjunction with clinicians and the
      practicalities of working within the clinical setting are considered to allow the
      full diagnostic potential of these techniques to be realised. A protocol is
      presented, which has been developed over three years and successfully deployed
      for quickly and accurately collecting breath samples from 323 respiratory
      patients recruited from 10 different secondary health care clinics. 

PMID- 25971864
TI  - Potential new treatments for EGFR-inhibitor-resistant NSCLC.

PMID- 25971862
TI  - The genetics and neurobiology of ESSENCE: The third Birgit Olsson lecture.
AB  - ESSENCE refers to early symptomatic syndromes eliciting neurodevelopmental
      clinical examinations. It includes a broad range of early onset
      neurodevelopmental disorders affecting more than 10% of children before 5 years
      of age. ESSENCE includes among others attention deficit hyperactivity disorder
      (ADHD), intellectual disability (ID) and autism spectrum disorders (ASD). Some
      degree of disability is the rule rather than the exception. The causes are
      heterogeneous ranging from extreme social deprivation, pre- and perinatal risk
      factors, genetic and metabolic diseases, immune and infectious disorders,
      nutritional factors, physical trauma, and postnatal toxic and environmental
      factors (and combinations/interactions of some or several of these). Treatments
      often involve a combination of psychoeducational interventions, home- and school
      based programmes, and medication. Here, I will first briefly review our main
      knowledge on the biological pathways associated with early onset
      neurodevelopmental disorders and will provide useful links to be informed of the
      progress in the field. Five main pathways are associated with ASD and ID:
      chromatin remodelling, cytoskeleton dynamics, mRNA translation, metabolism and
      synapse formation/function. I will then detail three propositions coming from
      institutions, researchers and/or communities of patients and families to foster
      research: 1) to use more dimensional and quantitative data than diagnostic
      categories; 2) to increase data sharing and research on genetic and brain
      diversity in human populations; 3) to involve patients and relatives as
      participants for research. Finally, I will provide examples of very stimulating
      initiatives towards a more inclusive world for individuals with ESSENCE.

PMID- 25971865
TI  - Pattern of change in telomere length: possible predictor of cancer.

PMID- 25971866
TI  - Children with advanced cancer need symptomatic treatments.

PMID- 25971867
TI  - Panobinostat active against diffuse intrinsic pontine glioma.

PMID- 25971868
TI  - Two-dimensional structure Au nanosheets are super active for the catalytic
      reduction of 4-nitrophenol.
AB  - Two-dimensional structure Au nanosheets with a polygon morphology and controlled
      thicknesses of ~15 nm, ~35 nm, and ~50 nm were successfully synthesized by a one
      step solution reduction method. Scanning and transmission electron microscopy
      (SEM and TEM), selected area electron diffraction (SEAD) analyses, and X-ray
      diffraction (XRD) were used to thoroughly study the structure and the formation
      mechanism of the nanosheets. The catalytic activity of the Au nanosheets was
      investigated for the reduction of 4-nitrophenol (4-NP) by UV-visible absorption
      spectroscopy. Against all expectation, the Au nanosheets with such a big lateral
      (more than 1 MUm) size exhibited superior catalytic activity on the selective
      reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of
      NaBH4. On the other hand, the catalytic activity does closely depend on the
      thickness of the nanosheets; that is, it decreases with increasing thickness. The
      reaction can be completed in less than 1 min when catalyzed by Au nanosheets
      about 15 nm thick. The 100% conversion efficiency was further demonstrated after
      two catalytic cycles with the thinnest Au nanosheets. 

PMID- 25971869
TI  - Genotypic and Environmental Impact on Natural Variation of Nutrient Composition
      in 50 Non Genetically Modified Commercial Maize Hybrids in North America.
AB  - This study was designed to assess natural variation in composition and
      metabolites in 50 genetically diverse non genetically modified maize hybrids
      grown at six locations in North America. Results showed that levels of
      compositional components in maize forage were affected by environment more than
      genotype. Crude protein, all amino acids except lysine, manganese, and beta
      carotene in maize grain were affected by environment more than genotype; however,
      most proximates and fibers, all fatty acids, lysine, most minerals, vitamins, and
      secondary metabolites in maize grain were affected by genotype more than
      environment. A strong interaction between genotype and environment was seen for
      some analytes. The results could be used as reference values for future nutrient
      composition studies of genetically modified crops and to expand conventional
      compositional data sets. These results may be further used as a genetic basis for
      improvement of the nutritional value of maize grain by molecular breeding and
      biotechnology approaches. 

PMID- 25971870
TI  - Endoscopic papillectomy and KRAS expression in the treatment of adenoma in the
      major duodenal papilla.
AB  - OBJECTIVE: The use of endoscopic papillectomy for resecting adenomas in the major
      duodenal papilla is increasing. This study focuses on the following three issues:
      Can endoscopic papillectomy be performed as a safe diagnostic and/or therapeutic
      procedure in biopsy-verified or suspected ampullary adenoma? Does expression of
      mutated KRAS in resected adenomatous tissue predict long-term outcome? What other
      factors may affect long-term outcome and should, therefore, be considered in
      decision making prior to endoscopic papillectomy? MATERIAL AND METHODS: Thirty
      six prospectively collected patients who underwent endoscopic papillectomy at
      Karolinska University Hospital between 2005 and 2014 were analyzed. RESULTS: The
      rate of exact agreement between the histomorphological grading of the endoscopic
      biopsies and the papillectomy specimens was low (48%). Obstructive jaundice at
      presentation increased the risk of undetected adenocarcinoma (RR = 3.98; 95% CI =
      1.46-10.85, p = 0.007). Lesions with malignancies were significantly larger (mean
      30.6 mm) than those where only adenomas were found (mean 14.4 mm, p = 0.001).
      Mutated KRAS was detected in 9 of the 36 post-papillectomy specimens, including 4
      of the 5 cases of ampullary adenocarcinoma. Eighteen cases were endoscopically
      cured after a mean follow-up period of 47 months (range 16-92 months).
      CONCLUSIONS: Endoscopic papillectomy is a valuable staging tool because of the
      limitations of endoscopic biopsy. Endoscopic papillectomy concomitantly offers a
      curative treatment for most patients with adenoma in the major duodenal papilla.
      Jaundice at presentation and large adenomas may indicate the presence of more
      advanced disease. Determination of mutated KRAS seems to be of limited value in
      predicting long-term outcome.

PMID- 25971871
TI  - Pharmacist's review and outcomes: Treatment-enhancing contributions tallied,
      evaluated, and documented (PROTECTED-UK).
AB  - PURPOSE: The purpose was to describe clinical pharmacist interventions across a
      range of critical care units (CCUs) throughout the United Kingdom, to identify
      CCU medication error rate and prescription optimization, and to identify the type
      and impact of each intervention in the prevention of harm and improvement of
      patient therapy. MATERIALS AND METHODS: A prospective observational study was
      undertaken in 21 UK CCUs from November 5 to 18, 2012. A data collection web
      portal was designed where the specialist critical care pharmacist reported all
      interventions at their site. Each intervention was classified as medication
      error, optimization, or consult. In addition, a clinical impact scale was used to
      code the interventions. Interventions were scored as low impact, moderate impact,
      high impact, and life saving. The final coding was moderated by blinded
      independent multidisciplinary trialists. RESULTS: A total of 20517 prescriptions
      were reviewed with 3294 interventions recorded during the weekdays. This resulted
      in an overall intervention rate of 16.1%: 6.8% were classified as medication
      errors, 8.3% optimizations, and 1.0% consults. The interventions were classified
      as low impact (34.0%), moderate impact (46.7%), and high impact (19.3%); and 1
      case was life saving. Almost three quarters of interventions were to optimize the
      effectiveness of and improve safety of pharmacotherapy. CONCLUSIONS: This
      observational study demonstrated that both medication error resolution and
      pharmacist-led optimization rates were substantial. Almost 1 in 6 prescriptions
      required an intervention from the clinical pharmacist. The error rate was
      slightly lower than an earlier UK prescribing error study (EQUIP). Two thirds of
      the interventions were of moderate to high impact.

PMID- 25971872
TI  - Bone mineral density and mandibular advancement as contributing factors for
      postoperative relapse after orthognathic surgery in patients with preoperative
      idiopathic condylar resorption: a prospective study with preliminary 1-year
      follow-up.
AB  - OBJECTIVES: The aim of this study was to analyze contributing factors for
      postoperative relapse after orthognathic surgery in patients with preoperative
      idiopathic condylar resorption (ICR). STUDY DESIGN: Sixteen female patients with
      mandibular retrognathism and ICR were included in this prospective study. For
      patient factors, serum 17 beta-estradiol (E2), bone mineral density, and the
      preoperative posterior condylar inclination were evaluated. Bone mineral density
      was measured using dual-energy x-ray absorptiometry (DEXA) bone densitometry and
      expressed by T-score. Surgical changes and postoperative relapse were measured
      with cephalometric analysis. The correlation between postoperative relapse and
      measured parameters was statistically analyzed. RESULTS: The lowest T-score
      exhibited a significant correlation with postoperative clockwise rotation and
      posterior relapse tendency of the mandible (P < .05). The amount of mandibular
      advancement showed a significant correlation with the postoperative clockwise
      rotation of the mandible (P < .05). CONCLUSIONS: The postoperative relapse
      tendency in patients with preoperative ICR is significantly related to the lowest
      T-score and the amount of mandibular advancement.

PMID- 25971873
TI  - nor-Mevaldic acid surrogates as selective antifungal agent leads against Botrytis
      cinerea. Enantioselective preparation of 4-hydroxy-6-(1-phenylethoxy)tetrahydro
      2H-pyran-2-one.
AB  - Solvent-free desymmetrisation of meso-dialdehyde 1 with chiral 1-phenylethan-1
      ol, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one (+)-3a
      with a 96:4 dr Deprotected lactone (+)-19a and the related racemic lactones 16a
      18a present a lactone moiety resembling the natural substrate of HMG-CoA
      reductase and their antifungal properties have been evaluated against the
      phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. These
      compounds were selectively active against B. cinerea, while inactive against C.
      gloeosporioides.

PMID- 25971874
TI  - Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory
      in mice: roles of N-methyl D-aspartate receptors and nitric oxide.
AB  - RATIONALE: Many peripheral diseases are associated with a decline in cognitive
      function. In this regard, there have been reports of patients with inflammatory
      bowel disease and an otherwise unexplained memory impairment. OBJECTIVES: We
      sought to assess the memory performance of mice with colitis. We also
      investigated the roles of N-methyl D-aspartate (NMDA) receptors and nitric oxide
      (NO) as possible mediators of colitis-induced amnesia. METHODS: To induce
      colitis, male NMRI mice were intrarectally injected with a solution containing
      dinitrobenzene sulfonic acid (DNBS; 4 mg in 100 MUl) under anesthesia. Three days
      after intrarectal DNBS instillation, spatial recognition and associative memories
      were assessed by the Y-maze and passive avoidance tasks, respectively. The NMDA
      antagonists, MK-801 and memantine, and the inducible NO synthase (iNOS)
      inhibitor, aminoguanidine, were injected intraperitoneally 45 min before the Y
      maze task. RESULTS: Induction of colitis by DNBS impaired spatial recognition
      memory in the Y-maze task but had no effect on step through latencies in the
      passive avoidance test. Colitis-induced amnesia was reversed by administering
      specific doses of MK-801 and memantine (30 MUg/kg and 1 mg/kg, respectively)
      suggesting dysregulated NMDA receptor activation as an underlying mechanism. No
      effect was seen with lower and higher doses of these drugs, resulting in a bell
      shaped dose response curve. Colitis-induced amnesia was also inhibited by
      aminoguanidine (50 mg/kg), implicating a role for iNOS activation and
      neuroinflammation in this phenomenon. CONCLUSION: DNBS-induced colitis impairs
      memory through NMDA receptor overstimulation and NO overproduction.

PMID- 25971876
TI  - Development of monosodium acetate-induced osteoarthritis and inflammatory pain in
      ageing mice.
AB  - Most conditions associated with ageing result from an age-related loss in the
      function of cells and tissues that maintain body homeostasis. In osteoarthritis
      (OA) patients, an inadequate response to stress or joint injury can lead to
      tissue destruction which can result in chronic pain. Here, we evaluated the
      development of monoiodoacetate (MIA)-induced OA in 3-, 15- and 22-month-old mice
      and assessed the pain-like behaviours and the spinal microglial changes
      associated with MIA administration. We observed that in aged mice, nocifensive
      behaviour was significantly attenuated in comparison to young adults despite
      similar knee joint pathology. Specifically referred mechanical allodynia
      associated with the MIA initial inflammatory phase (0-10 days) was significantly
      attenuated in 22-month-old mice. In contrast, the late phase of MIA-induced
      mechanical allodynia was comparable between age groups. Significant increase of
      microglia cell numbers was detected in 3, but not 15- and 22-month-old spinal
      cords. Furthermore, in the zymosan model of acute inflammation, mechanical
      allodynia was attenuated, and microglial response was less robust in 22 compared
      to 3-month-old mice. This study suggests that nocifensive responses to damaging
      stimuli are altered with advancing age and microglial response to peripheral
      damage is less robust.

PMID- 25971875
TI  - Norepinephrine-enhancing antidepressant exposure associated with reduced
      antiviral effect of interferon alpha on hepatitis C.
AB  - RATIONALE: Major depressive disorder is a common consequence of exposure to the
      pro-inflammatory cytokine interferon alpha, which is treated effectively with
      antidepressant medication. Antidepressant mode of action may conflict with
      interferon alpha's mechanism in treating hepatitis C however. OBJECTIVES: The
      purpose of this study is to prospectively explore, in a large naturalistic
      cohort, whether antidepressant exposure influenced end of treatment response of
      hepatitis C to interferon alpha. METHODS: Two hundred thirty-nine patients
      infected with chronic hepatitis C and due to receive treatment were recruited.
      All participants initiated peg-interferon-2-alpha 180 MUg weekly sub-cutaneously
      plus oral ribavirin 800-1200 mg daily. Participants were assessed for DSM-IV
      major depression at baseline and four weekly during treatment. RESULTS: 32.6 % of
      the cohort was exposed to an antidepressant (serotonin-reuptake inhibitor: other
      categorised antidepressants 49:29). At baseline, 3.8 % had major depression and
      55.2 % developed major depression during interferon alpha treatment. Exposure to
      an antidepressant not classified as a serotonin-reuptake inhibitor, of which all
      were norepinephrine-enhancing (OR 0.15, 95 % CI 0.04-0.60) and having a past
      history of psychiatric disorder (OR 4.41, 95 % CI 1.39-13.96) independently
      reduced the likelihood of end of treatment response. Serotonin-reuptake inhibitor
      exposure did not influence end of treatment response (OR 1.21, 95 % CI 0.35
      4.19), neither did major depression at baseline (OR 2.31, 95 % CI 0.55-9.60) or
      during treatment (OR 0.69, 95 % CI 0.36-1.33). CONCLUSIONS: Our findings support
      a lack of conflict of therapeutic mechanism of serotonin-reuptake inhibitor
      antidepressants with interferon alpha in treating hepatitis C, which may include
      inflammatory influence. This appears not to be true for norepinephrine-enhancing
      antidepressant types and warrants investigation using more direct methods.

PMID- 25971877
TI  - Understanding the individual responsiveness to resistance training periodization.
AB  - This study was designed to compare the effects of linear periodization (LP) and
      undulating periodization (UP) on functional capacity, neuromuscular function,
      body composition, and cytokines in elderly sedentary women. We also aimed to
      identify the presence of high responders (HR), medium responders (MR), and low
      responders (LR) for irisin, interleukin-1 beta (IL-1beta), toll-like receptor-4
      (TLR-4), and brain-derived neurotrophic factor (BDNF) to resistance training
      (RT). Forty-nine elderly women were assigned to a control group, LP, and UP
      scheme. Functional capacity, body composition, maximal strength, irisin, TLR-4,
      BDNF, and IL-1beta were evaluated. Both periodization models were effective in
      improving 45 degrees  leg press 1RM, chair-stand, arm curl, and time-up and go
      tests, with no significant differences in body composition and cytokines.
      Furthermore, HR, MR, and LR were identified for irisin, IL-1beta, TLR-4, and
      BDNF, with differences between groups and moments. This study provides evidence
      that both periodization models were effective in improving functional capacity
      and neuromuscular function, with no effect on body composition and cytokines
      (probably as a consequence of the different responsiveness). Furthermore, for the
      first time, HR, MR, and LR were identified for irisin, IL1-beta, TLR-4, and BDNF
      in response to RT. 

PMID- 25971878
TI  - The interplay between uncertainty monitoring and working memory: Can
      metacognition become automatic?
AB  - The uncertainty response has grounded the study of metacognition in nonhuman
      animals. Recent research has explored the processes supporting uncertainty
      monitoring in monkeys. It has revealed that uncertainty responding, in contrast
      to perceptual responding, depends on significant working memory resources. The
      aim of the present study was to expand this research by examining whether
      uncertainty monitoring is also working memory demanding in humans. To explore
      this issue, human participants were tested with or without a cognitive load on a
      psychophysical discrimination task that included either an uncertainty response
      (allowing the participant to decline difficult trials) or a middle-perceptual
      response (labeling the same intermediate trial levels). The results demonstrated
      that cognitive load reduced uncertainty responding, but increased middle
      responding. However, this dissociation between uncertainty and middle responding
      was only observed when participants either lacked training or had very little
      training with the uncertainty response. If more training was provided, the effect
      of load was small. These results suggest that uncertainty responding is resource
      demanding, but with sufficient training, human participants can respond to
      uncertainty either by using minimal working memory resources or by effectively
      sharing resources. These results are discussed in relation to the literature on
      animal and human metacognition. 

PMID- 25971879
TI  - The Role of Oxidative Stress in Gastrointestinal Tract Tissues Induced by Arsenic
      Toxicity in Cocks.
AB  - Arsenic (As) is a widely distributed trace element which is known to be
      associated with numerous adverse effects on human beings and animals. Arsenic
      trioxide (As2O3) is an inorganic arsenical-containing toxic compound. The effect
      of excessive amounts of As2O3 exposure on gastrointestinal tract tissue damage in
      cocks is still unknown. This study was conducted to investigate the effect of
      As2O3 exposure on gastrointestinal tract tissue damage in cocks. In total, 72 1
      day-old male Hyline cocks were randomly divided into four groups and fed either a
      commercial diet or an As2O3 supplement diet containing 7.5, 15, and 30 mg/kg
      As2O3. The experiment lasted for 90 days and gastrointestinal tract tissue
      samples (gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum)
      were collected at 30, 60, and 90 days. Catalase (CAT), glutathione (GSH), and
      glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA) contents; and
      hydroxyl radical (OH.)-mediated inhibition were examined. Furthermore, the
      results demonstrated that MDA content in the gastrointestinal tract was
      increased, while the activities of CAT, GSH, and GSH-Px and the ability to resist
      OH. was decreased in the As2O3 treatment groups. Extensive damage was observed in
      the gastrointestinal tract. These findings indicated that As2O3 exposure caused
      oxidative damage in the gastrointestinal tract of cocks due to alterations in
      antioxidant enzyme activities and elevation of free radicals. 

PMID- 25971880
TI  - Erratum to: Effect of Thermocycling on Nickel Release from Orthodontic Arch
      Wires: An In Vitro Study.

PMID- 25971881
TI  - Early investigational therapeutics for gastrointestinal motility disorders: from
      animal studies to Phase II trials.
AB  - INTRODUCTION: The most common gastrointestinal disorders that include evidence of
      dysmotility include: gastroparesis, the lower functional gastrointestinal
      disorders associated with altered bowel function (such as chronic [functional]
      diarrhea, chronic idiopathic constipation) and opioid-induced constipation. These
      conditions, which are grouped as gastrointestinal motility and functional
      disorders, are characterized by abnormal motor, sensory or secretory functions
      that alter bowel function and result in a significant disease burden, since
      currently available treatments do not completely alleviate symptoms. New drugs
      are being developed for these disorders, targeting mechanisms involved in the
      pathophysiology of these diseases, specifically, motor function, intestinal
      secretion and bile acid modulation. AREAS COVERED: The article provides a brief
      overview of motility disorders and the drugs approved and currently available for
      these indications. It also provides an evaluation of the efficacy, safety and
      possible mechanisms of the drugs currently under investigation for the treatment
      of gastroparesis, chronic diarrhea, chronic idiopathic constipation and opioid
      induced constipation, based on animal to Phase II studies. Medications with
      complete Phase III trials are excluded from this discussion. EXPERT OPINION:
      Treatment of gastrointestinal motility disorders requires the understanding of
      the pathophysiological mechanisms, biomarkers to identify subgroups of these
      disorders and robust pharmacological studies from animal to Phase II studies.
      These are prerequisites for the development of efficacious medications and
      individualizing therapy in order to enhance the treatment of these patients.

PMID- 25971883
TI  - Executive Function in Low Birth Weight Preschoolers: The Moderating Effect of
      Parenting.
AB  - Previous meta-analyses have identified moderate deficits in executive function
      (EF) in children born low birth weight (birth weight < 2500 g; LBW). The current
      study tests the joint contribution of LBW and parenting quality on trajectories
      of executive function in 1121 preschoolers (50 % boys). We estimated latent
      growth curve models to represent linear change in EF from 3 to 5 years of age,
      and tested the impact of LBW, parenting, and their interaction, on the estimated
      trajectory parameters. Although LBW was related to lower EF ability at all three
      time points (Cohen's d = 0.43-0.55), LBW children who experienced high levels of
      sensitive parenting in toddlerhood exhibited faster rates of improvement in EF,
      and were virtually indistinguishable from their normal birth weight peers by age
      5. On the other hand, LBW children who experienced below average levels of
      sensitive parenting showed lasting deficits in EF ability. These findings suggest
      that sensitive parenting may buffer LBW children from lasting deficits in EF.
      Implications of these findings for future interventions are discussed.

PMID- 25971884
TI  - The Prospective Role of Cognitive Appraisals and Social Support in Predicting
      Children's Posttraumatic Stress.
AB  - Although both social support and cognitive appraisals are strong predictors of
      children's posttraumatic adjustment, understanding of the interplay between these
      factors is limited. We assessed whether cognitive appraisals mediated the
      relationship between social support and symptom development, as predicted by
      cognitive models of posttraumatic stress disorder (PTSD). Ninety seven children
      (Mean age = 12.08 years) were assessed at one month and six months following a
      single incident trauma. We administered self-report measures of cognitive
      appraisals, social support, and a diagnostic interview for PTSD. Results
      indicated that cognitive appraisals at one month post-trauma mediated the
      relationship between social support at one month post-trauma, and PTSD severity
      at follow-up. Differences in this relationship were observed between child
      reported social support and parent-rated ability to provide support. Firm
      evidence was provided for the application of cognitive models of PTSD to
      children.

PMID- 25971886
TI  - Adequate sedation with single-dose dexmedetomidine in patients undergoing
      transurethral resection of the prostate with spinal anaesthesia: a dose-response
      study by age group.
AB  - BACKGROUND: Dexmedetomidine (DMT), a highly selective alpha2-adrenoceptor
      agonist, has been used safely as a sedative in patients under regional
      anesthesia. The purpose of this study was to determine the 50% effective dose
      (ED50) of single-dose DMT to induce adequate light sedation in elderly patients
      in comparison with younger patients undergoing transurethral resection of the
      prostate (TURP) with spinal anesthesia. METHODS: Forty-two male patients were
      recruited. The young age group (Group Y) included patients 45 to 64 years old and
      the old age group (Group O) included patients 65 to 78 years old. After the
      spinal anesthesia was performed, a pre-calculated dose of DMT was administered
      for 10 min. The Observer's Assessment of Alertness/Sedation (OAA/S) scale,
      bispectral index score (BIS) were assessed then at 2-min intervals for 20 min. A
      modified Dixon's up-and-down method was used to determine the ED50 of the drug
      for light sedation (OAA/S score 3/4). In the recovery room, regression times of
      the motor and sensory blocks were recorded. RESULTS: The ED50 of DMT was 0.25
      (95% C.I. 0.15-0.35) MUg/kg in Group O and 0.35 (95% C.I. 0.35-0.45) MUg/kg in
      Group Y (p = 0.002). The ED95 was 33% lower in Group O compare with Group Y (0.38
      (95% C.I. 0.29-0.39) MUg/kg vs. 0.57 (95% C.I. 0.49-0.59) MUg/kg). The regression
      time of sensory block was longer in Group O than in Group Y (109.0 +/- 40.2 min
      vs. 80.0 +/- 31.6 min) (p = 0.014). CONCLUSION: The single-dose of DMT for light
      sedation was lower by 21% in Group O compare with Group Y underwent TURP with
      spinal anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01665586. Registered July 31, 2012.

PMID- 25971887
TI  - Oral administration of cytosolic PLA2 inhibitor arachidonyl trifluoromethyl
      ketone ameliorates cauda equina compression injury in rats.
AB  - BACKGROUND: Phospholipase A2 (PLA2)-derived proinflammatory lipid mediators such
      as prostaglandin E2 (PGE2), leukotrienes B4 (LTB4), lysophosphatidylcholine
      (LPC), and free fatty acids (FFA) are implicated in spinal cord injury (SCI)
      pathologies. Reducing the levels of these injurious bioactive lipid mediators is
      reported to ameliorate SCI. However, the specific role of the group IVA isoform
      of PLA2 cytosolic PLA2 (cPLA2) in lumbar spinal canal stenosis (LSS) due to cauda
      equina compression (CEC) injury is not clear. In this study, we investigated the
      role of cPLA2 in a rat model of CEC using a non-toxic cPLA2-preferential
      inhibitor, arachidonyl trifluoromethyl ketone (ATK). METHODS: LSS was induced in
      adult female rats by CEC procedure using silicone blocks within the epidural
      spaces of L4 to L6 vertebrae. cPLA2 inhibitor ATK (7.5 mg/kg) was administered by
      oral gavage at 2 h following the CEC. cPLA2-derived injurious lipid mediators and
      the expression/activity of cPLA2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2
      (COX-2) were assessed. ATK-treated (CEC + ATK) were compared with vehicle-treated
      (CEC + VEH) animals in terms of myelin levels, pain threshold, and motor
      function. RESULTS: ATK treatment of CEC animals reduced the phosphorylation of
      cPLA2 (pcPLA2) determined by Western blot, improved locomotor function evaluated
      by rotarod task, and reduced pain threshold evaluated by mechanical hyperalgesia
      method. Levels of FFA and LPC, along with PGE2 and LTB4, were reduced in CEC +
      ATK compared with CEC + VEH group. However, ATK treatment reduced neither the
      activity/expression of 5-LOX nor the expression of COX-2 in CEC + VEH animals.
      Increased cPLA2 activity in the spinal cord from CEC + VEH animals correlated
      well with decreased spinal cord as well as cauda equina fiber myelin levels,
      which were restored after ATK treatment. CONCLUSION: The data indicate that cPLA2
      activity plays a significant role in tissue injury and pain after LSS. Reducing
      the levels of proinflammatory and tissue damaging eicosanoids and the deleterious
      lipid mediator LPC shows therapeutic potential. ATK inhibits cPLA2 activity,
      thereby decreasing the levels of injurious lipid mediators, reducing pain,
      improving functional deficits, and conferring protection against LSS injury.
      Thus, it shows potential for preclinical evaluation in LSS.

PMID- 25971888
TI  - Surgical repair of a giant congenital right atrial aneurysm: a case report.
AB  - Giant congenital right atrial aneurysms are rare defects of the heart. Though
      usually asymptomatic, they can be potentially life-threatening. Major risks
      include heart failure, supraventricular arrhythmias, rupture of the wall of the
      aneurysm. This defect is usually diagnosed incidentally. It is commonly found
      when transthoracic echocardiography or chest X-ray is performed. In some cases
      computed tomography or cardiac magnetic resonance imaging is needed to establish
      the diagnosis. Potential therapeutic options include surgery, catheter ablation
      and conservative follow-up. Currently preferred method for correcting this defect
      is surgical excision of the aneurysm, when surgical indications are met. In this
      article we describe a successful aneurysmectomy performed on a 16-month old
      female infant, who at the time of hospitalization presented with severe heart
      failure and symptoms of cardiac tamponade.

PMID- 25971889
TI  - Quercetin inhibits HGF/c-Met signaling and HGF-stimulated melanoma cell migration
      and invasion.
AB  - BACKGROUND: Melanoma is notorious for its propensity to metastasize, which makes
      treatment extremely difficult. Receptor tyrosine kinase c-Met is activated in
      human melanoma and is involved in melanoma progression and metastasis. Hepatocyte
      growth factor (HGF)-mediated activation of c-Met signaling has been suggested as
      a therapeutic target for melanoma metastasis. Quercetin is a dietary flavonoid
      that exerts anti-metastatic effect in various types of cancer including melanoma.
      In a previous report, we demonstrated that quercetin inhibited melanoma cell
      migration and invasion in vitro, and prevented melanoma cell lung metastasis in
      vivo. In this study, we sought to determine the involvement of HGF/c-Met
      signaling in the anti-metastatic action of quercetin in melanoma. METHODS:
      Transwell chamber assay was conducted to determine the cell migratory and
      invasive abilities. Western blotting was performed to determine the expression
      levels and activities of c-Met and its downstream molecules. And immunoblotting
      was performed in BS(3) cross-linked cells to examine the homo-dimerization of c
      Met. Quantitative real-time PCR analysis was carried out to evaluate the mRNA
      expression level of HGF. Transient transfection was used to overexpress PAK or
      FAK in cell models. Student's t-test was used in analyzing differences between
      two groups. RESULTS: Quercetin dose-dependently suppressed HGF-stimulated
      melanoma cell migration and invasion. Further study indicated that quercetin
      inhibited c-Met phosphorylation, reduced c-Met homo-dimerization and decreased c
      Met protein expression. The effect of quercetin on c-Met expression was
      associated with a reduced expression of fatty acid synthase. In addition,
      quercetin suppressed the phosphorylation of c-Met downstream molecules including
      Gab1 (GRB2-associated-binding protein 1), FAK (Focal Adhesion Kinase) and PAK
      (p21-activated kinases). More importantly, overexpression of FAK or PAK
      significantly reduced the inhibitory effect of quercetin on the migration of the
      melanoma cells. CONCLUSIONS: Our findings suggest that suppression of the HGF/c
      Met signaling pathway contributes to the anti-metastatic action of quercetin in
      melanoma.

PMID- 25971890
TI  - National early warning score at Emergency Department triage may allow earlier
      identification of patients with severe sepsis and septic shock: a retrospective
      observational study.
AB  - INTRODUCTION: Severe sepsis and septic shock (SS) are time-critical medical
      emergencies that affect millions of people in the world. Earlier administration
      of antibiotics has been shown to reduce mortality from SS; however, the
      initiation of early resuscitation requires recognition that a patient may have
      sepsis. Early warning scores (EWS) are broadly used to detect patient
      deterioration, but to date have not been evaluated to detect patients at risk for
      SS. The purpose of our study was to look at the relationship between the initial
      national EWS (NEWS) in the emergency department (ED) and the diagnosis of SS.
      METHODS: We performed a retrospective, single-centre, observational study in the
      ED of an urban university hospital with an annual attendance of 140,000 patients.
      We aimed to include 500 consecutive non-trauma adult patients presenting to the
      ED with Manchester Triage System (MTS) category 1-3. The final diagnosis was
      taken from either the ED medical records or the hospital discharge summary. For
      all NEWS, the sensitivity and specificity to detect patients with SS was
      calculated. RESULTS: A total of 500 patients were included, 27 patients (5.4%)
      met the criteria for SS. The area under the curve (AUC) for NEWS to identify
      patient at risk for SS is 0.89 (95% CI 0.84 to 0.94). A NEWS of 3 or more at ED
      triage has a sensitivity of 92.6% (95% CI 74.2% to 98.7%) and a specificity of
      77% (95% CI 72.8% to 80.6%) to detect patients at risk for SS at ED triage.
      CONCLUSIONS: A NEWS of 3 or more at ED triage may be the trigger to
      systematically screen the patient for SS, which may ultimately lead to early
      recognition and treatment.

PMID- 25971891
TI  - A survey of the surgical treatment of congenital and developmental cataracts in
      Japan.
AB  - PURPOSE: To understand the current practice pattern for the surgical treatment of
      congenital/developmental cataracts in Japan. METHODS: A mail questionnaire was
      sent to facilities engaged in the surgical treatment of congenital cataracts in
      Japan. RESULTS: Thirty-four facilities reported their preferred methods for the
      surgical treatment of congenital cataracts, including data from 809 eyes of 508
      patients who had undergone surgery. More than 85% of the respondents answered
      that they would consider surgery even if the visual prognosis was not promising
      because of possible form-deprivation amblyopia. The most commonly performed
      surgical maneuvers were scleral tunnel incision (88.4%), 3.0-mm or smaller
      incision (78.8%), manual anterior continuous curvilinear capsulorhexis (90.2%
      success rate), posterior capsulotomy (92.5% for patients aged <=6 years),
      anterior vitrectomy by the limbal approach (85.9% for patients aged <=6 years),
      and wound closure with sutures (93.2%). Posterior capsulotomy and vitrectomy were
      not usually performed in patients aged >6 years. Implantation of an intraocular
      lens (IOL) was mostly indicated in patients aged 2 years or older. Implantation
      of an acrylic foldable IOL (76.6%) into the capsular bag (89.7%) was the most
      common practice among the surgeons. CONCLUSIONS: Small incision surgery with
      implantation of an acrylic foldable IOL into the capsular bag combined with
      posterior capsulotomy was the preferred surgical treatment of choice for
      congenital/developmental cataracts.

PMID- 25971892
TI  - "Like a lots happened with my whole childhood": violence, trauma, and addiction
      in pregnant and postpartum women from Vancouver's Downtown Eastside.
AB  - BACKGROUND: Women living in poor and vulnerable neighbourhoods like Vancouver's
      Downtown Eastside (DTES) face multiple burdens related to the social determinants
      of health. Many of them struggle with addiction, are involved in the sex trade
      and experience homelessness and gender-based violence. Such evidence suggests
      that psychological trauma is also a common experience for these women. METHODS:
      The purpose of this qualitative study was to explore themes and subjective
      perspectives of trauma and gender-based violence in women who lived in an
      impoverished neighbourhood and struggled with substance use during pregnancy and
      early motherhood. We interviewed 27 individuals accessing harm reduction services
      for pregnant and postpartum women in Vancouver, Canada. RESULTS: Key themes that
      emerged from these women's narratives highlighted the ubiquity of multiple and
      continuing forms of adversities and trauma from childhood to adulthood, in a
      variety of contexts, through a variety of offenders and on multiple levels. Both
      individual and environmental/structural conditions mutually intensified each
      other, interfering with a natural resolution of trauma-related symptoms and
      substance use. Women were also concerned that trauma could be passed on from one
      generation to the next, yet expressed hesitation when asked about their interest
      in trauma-specific counselling. CONCLUSIONS: In offering harm reduction services
      for poor and marginalized women, it is clear that an understanding of trauma must
      be integrated. It is recommended that service providers integrate trauma-informed
      care into their programme in order to offer this service in a trusted
      environment. However, it is also necessary to shift the focus from the individual
      to include environmental, social, economic and policy interventions on multiple
      levels and from issues of drug use and reduction of drug-related harms to include
      issues of gendered vulnerabilities and human rights.

PMID- 25971893
TI  - Improved Alkane Production in Nitrogen-Fixing and Halotolerant Cyanobacteria via
      Abiotic Stresses and Genetic Manipulation of Alkane Synthetic Genes.
AB  - Cyanobacteria possess the unique capacity to produce alkane. In this study,
      effects of nitrogen deficiency and salt stress on biosynthesis of alkanes were
      investigated in three kinds of cyanobacteria. Intracellular alkane accumulation
      was increased in nitrogen-fixing cyanobacterium Anabaena sp. PCC7120, but
      decreased in non-diazotrophic cyanobacterium Synechococcus elongatus PCC7942 and
      constant in a halotolerant cyanobacterium Aphanothece halophytica under nitrogen
      deficient condition. We also found that salt stress increased alkane accumulation
      in Anabaena sp. PCC7120 and A. halophytica. The expression levels of two alkane
      synthetic genes were not upregulated significantly under nitrogen deficiency or
      salt stress in Anabaena sp. PCC7120. The transformant Anabaena sp. PCC7120 cells
      with additional alkane synthetic gene set from A. halophytica increased
      intracellular alkane accumulation level compared to control cells. These results
      provide a prospect to improve bioproduction of alkanes in nitrogen-fixing
      halotolerant cyanobacteria via abiotic stresses and genetic engineering. 

PMID- 25971894
TI  - The "Motor Band Sign:" Susceptibility-Weighted Imaging in Amyotrophic Lateral
      Sclerosis.

PMID- 25971895
TI  - A carbon nanotube wall membrane for water treatment.
AB  - Various forms of carbon nanotubes have been utilized in water treatment
      applications. The unique characteristics of carbon nanotubes, however, have not
      been fully exploited for such applications. Here we exploit the characteristics
      and corresponding attributes of carbon nanotubes to develop a millimetre-thick
      ultrafiltration membrane that can provide a water permeability that approaches
      30,000 l m(-2) h(-1) bar(-1), compared with the best water permeability of 2,400
      l m(-2) h(-1) bar(-1) reported for carbon nanotube membranes. The developed
      membrane consists only of vertically aligned carbon nanotube walls that provide 6
      nm-wide inner pores and 7-nm-wide outer pores that form between the walls of the
      carbon nanotubes when the carbon nanotube forest is densified. The experimental
      results reveal that the permeance increases as the pore size decreases. The
      carbon nanotube walls of the membrane are observed to impede bacterial adhesion
      and resist biofilm formation.

PMID- 25971896
TI  - The role of intraoperative ultrasonography in the diagnosis and management of
      focal hepatic lesions.
AB  - Intraoperative ultrasonography (IOUS) has been widely utilized in hepatic surgery
      both as a diagnostic technique and in the course of treatment. Since IOUS
      involves direct-contact imaging of the target organ, it can provide high spatial
      resolution without interference from the surrounding structures. Therefore, IOUS
      may improve the detection, characterization, localization, and local staging of
      hepatic tumors. IOUS is also a real-time imaging modality capable of providing
      interactive information and valuable guidance in a range of procedures. Recently,
      contrast-enhanced IOUS, IOUS elastography, and IOUS-guided hepatic surgery have
      attracted increasing interest and are expected to lead to the broader
      implementation of IOUS. Herein, we review the various applications of IOUS in the
      diagnosis and management of focal hepatic lesions. 

PMID- 25971898
TI  - Prenatal diagnosis of hypophosphatasia congenita using ultrasonography.
AB  - Congenital hypophosphatasia is a rare fatal skeletal dysplasia. Antenatal
      determinants of Epub ahead of print lethality include small thoracic
      circumference with pulmonary hypoplasia and severe micromelia. These features
      were present in the fetus of a 25-year-old female who came for an anomaly scan in
      her second trimester of pregnancy. Additional findings of generalized
      demineralization and osteochondral spurs led to the diagnosis of hypophosphatasia
      congenita. The pregnancy was terminated, and the findings were confirmed on
      autopsy. Common differential diagnoses with clues to diagnose the above mentioned
      condition have been discussed here. Early and accurate detection of this medical
      condition is important as no treatment has been established for this condition.
      Therefore, antenatal ultrasonography helps in diagnosing and decision making with
      respect to the current pregnancy and lays the foundation for the genetic
      counseling of the couple. 

PMID- 25971897
TI  - Parathyroid ultrasonography: the evolving role of the radiologist.
AB  - Previously, radiologists played a limited role in the treatment of parathyroid
      disease, primary focusing on the preoperative localization of parathyroid lesions
      responsible for hyperparathyroidism. But, the widespread use of high-resolution
      ultrasound has lead to the increasing detection of parathyroid incidentalomas
      (PTIs). Consequently, radiologists may be required to differentiate PTIs from
      thyroid lesions, which is most reliably accomplished through the fine needle
      aspiration-parathyroid hormone analysis. Various nonsurgical treatment modalities
      for hyperfunctioning parathyroid lesions have been developed with some efficacy.
      Especially for symptomatic nonfunctioning parathyroid cysts, simple aspiration is
      a first-line procedure for diagnosis and treatment, while ethanol ablation is a
      subsequent treatment modality for recurrent cases. 

PMID- 25971899
TI  - The value of the mean peak systolic velocity of the superior thyroidal artery in
      the differential diagnosis of thyrotoxicosis.
AB  - PURPOSE: The aim of this study was to validate the superior thyroidal artery mean
      peak systolic velocity (STA-mPSV) as an alternative to other diagnostic
      parameters in the differentiation of the causes of thyrotoxicosis in Korean
      patients. METHODS: This study was conducted with newly diagnosed and untreated
      thyrotoxic patients. Forty patients were diagnosed with Graves disease (GD) and
      20 patients with destructive thyroiditis (DT). Another 60 healthy subjects
      without thyroid disease participated as the control group. Blood samples were
      taken to evaluate the thyroid function and thyroid autoantibodies (TRAb). Twenty
      four hour radioactive iodine uptake (RAIU) scanning was performed to confirm GD
      or DT. The STA-mPSV was measured using color Doppler ultrasonography. RESULTS:
      The STA-mPSV was significantly higher in the untreated GD group than in the DT
      group (GD, 78.96+/-29.04 cm/sec; DT, 29.97+/-14.67 cm/sec; control, 17.55+/-4.99
      cm/sec; P<0.001). The area under the curve (AUC) of the STA-mPSV for the
      differential diagnosis of untreated GD and DT was 0.9506 (optimal cutoff value,
      41.3 cm/sec; sensitivity, 95%, 38/40; specificity, 85%, 17/20) in the receiver
      operating characteristic analysis. The AUC values of the STA-mPSV, RAIU, and TRAb
      were 0.9506, 1, and 0.9988, respectively (P=0.159). CONCLUSION: In clinical
      practice, the STA-mPSV has a diagnostic value similar to that of the TRAb and 24
      hour RAIU in the differential diagnosis of newly diagnosed Korean thyrotoxic
      patients.

PMID- 25971900
TI  - Current status of automated breast ultrasonography.
AB  - Breast ultrasonography (US) is currently considered the first-line examination in
      the detection Epub ahead of print and characterization of breast lesions.
      However, conventional handheld US (HHUS) has several limitations such as operator
      dependence and the requirement of a considerable amount of radiologist time for
      whole-breast US. Automated breast US (ABUS), recently approved by the United
      States Food and Drug Administration for screening purposes, has several
      advantages over HHUS, such as higher reproducibility, less operator dependence,
      and less required physician time for image acquisition. In addition, ABUS
      provides both a coronal view and a relatively large field of view. Recent studies
      have reported that ABUS is promising in US screening for women with dense breasts
      and can potentially replace handheld second-look US in a preoperative setting. 

PMID- 25971901
TI  - Postoperative ultrasonography of the musculoskeletal system.
AB  - Ultrasonography of the postoperative musculoskeletal system plays an important
      role in the Epub ahead of print accurate diagnosis of abnormal lesions in the
      bone and soft tissues. Ultrasonography is a fast and reliable method with no
      harmful irradiation for the evaluation of postoperative musculoskeletal
      complications. In particular, it is not affected by the excessive metal artifacts
      that appear on computed tomography or magnetic resonance imaging. Another benefit
      of ultrasonography is its capability to dynamically assess the pathologic
      movement in joints, muscles, or tendons. This article discusses the frequent
      applications of musculoskeletal ultrasonography in various postoperative
      situations including those involving the soft tissues around the metal hardware,
      arthroplasty, postoperative tendons, recurrent soft tissue tumors, bone unions,
      and amputation surgery. 

PMID- 25971902
TI  - Vernacular dominance in folk taxonomy: a case study of ethnospecies in medicinal
      plant trade in Tanzania.
AB  - BACKGROUND: Medicinal plants are traded as products with vernacular names, but
      these folk taxonomies do not always correspond one-to-one with scientific plant
      names. These local species entities can be defined as ethnospecies and can match,
      under-differentiate or over-differentiate as compared to scientific species.
      Identification of plant species in trade is further complicated by the processed
      state of the product, substitution and adulteration. In countries like Tanzania,
      an additional dimension to mapping folk taxonomies on scientific names is added
      by the multitude of ethnicities and languages of the plant collectors, traders
      and consumers. This study aims to elucidate the relations between the most common
      vernacular names and the ethnicity of the individual traders among the medicinal
      plant markets in Dar es Salaam and Tanga regions in Tanzania, with the aim of
      understanding the dynamics of vernacular names in plant trade. METHODS: A total
      of 90 respondents were interviewed in local markets using semi-structured
      interviews. The ethnicity of each respondent was recorded, as well as the
      language of each ethnospecies mentioned during the interviews. Voucher
      collections and reference literature were used to match ethnospecies across
      languages. RESULTS: At each market, the language of the majority of the vendors
      dominates the names for medicinal products. The dominant vendors often represent
      the major ethnic groups of that region. Independent of their ethnicity, vendors
      offer their products in the dominant language of the specific region without
      apparently leading to any confusion or species mismatching. CONCLUSIONS:
      Middlemen, traders and vendors adapt their folk classifications to those of the
      ethnic groups of the region where they conduct their trade, and to the ethnicity
      of their main customers. The names in the language of the traders are not
      forgotten, but relegated in favor of the more salient names of the dominant
      tribe.

PMID- 25971904
TI  - Synaptic Multivesicular Release in the Cerebellar Cortex: Its Mechanism and Role
      in Neural Encoding and Processing.
AB  - The number of synaptic vesicles released during fast release plays a major role
      in determining the strength of postsynaptic response. However, it remains
      unresolved how the number of vesicles released in response to action potentials
      is controlled at a single synapse. Recent findings suggest that the Cav2.1
      subtype (P/Q-type) of voltage-gated calcium channels is responsible for inducing
      presynaptic multivesicular release (MVR) at rat cerebellar glutamatergic synapses
      from granule cells to molecular layer interneurons. The topographical distance
      from Cav2.1 channels to exocytotic Ca(2+) sensors is a critical determinant of
      MVR. In physiological trains of presynaptic neurons, MVR significantly impacts
      the excitability of postsynaptic neurons, not only by increasing peak amplitude
      but also by prolonging decay time of the postsynaptic currents. Therefore, MVR
      contributes additional complexity to neural encoding and processing in the
      cerebellar cortex. 

PMID- 25971905
TI  - Core outcome sets and trial registries.
AB  - Some reasons for registering trials might be considered as self-serving, such as
      satisfying the requirements of a journal in which the researchers wish to publish
      their eventual findings or publicising the trial to boost recruitment. Registry
      entries also help others, including systematic reviewers, to know about ongoing
      or unpublished studies and contribute to reducing research waste by making it
      clear what studies are ongoing. Other sources of research waste include
      inconsistency in outcome measurement across trials in the same area, missing data
      on important outcomes from some trials, and selective reporting of outcomes. One
      way to reduce this waste is through the use of core outcome sets: standardised
      sets of outcomes for research in specific areas of health and social care. These
      do not restrict the outcomes that will be measured, but provide the minimum to
      include if a trial is to be of the most use to potential users. We propose that
      trial registries, such as ISRCTN, encourage researchers to note their use of a
      core outcome set in their entry. This will help people searching for trials and
      those worried about selective reporting in closed trials. Trial registries can
      facilitate these efforts to make new trials as useful as possible and reduce
      waste. The outcomes section in the entry could prompt the researcher to consider
      using a core outcome set and facilitate the specification of that core outcome
      set and its component outcomes through linking to the original core outcome set.
      In doing this, registries will contribute to the global effort to ensure that
      trials answer important uncertainties, can be brought together in systematic
      reviews, and better serve their ultimate aim of improving health and well-being
      through improving health and social care. 

PMID- 25971906
TI  - The role of T-cell phenotype and T-cell receptor rearrangement in the diagnosis
      of T-cell malignancies: author's reply.

PMID- 25971907
TI  - Obatoclax in combination with fludarabine and rituximab is well-tolerated and
      shows promising clinical activity in relapsed chronic lymphocytic leukemia.
AB  - Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins.
      This phase 1 study combining obatoclax with FR was undertaken in chronic
      lymphocytic leukemia (CLL) patients relapsed after at least one prior therapy.
      Obatoclax was given as a 3-h infusion on days 1 and 3 and escalated through three
      dose levels, with standard dose FR days 1-5. Thirteen patients were enrolled,
      with a median of two prior therapies. One dose-limiting toxicity (DLT) of a 2
      week treatment delay for persistent grade 2-3 neutropenia was observed at the
      highest obatoclax dose (20 mg/m2), but no maximum tolerated dose (MTD) was
      reached. The overall response rate (ORR) was 85%, with 15% complete responses
      (CRs) by NCI-96 criteria and 54% by IWCLL 2008 criteria. Median time to
      progression was 20 months. It is concluded that obatoclax can be safely
      administered to relapsed CLL patients in combination with FR and shows promising
      clinical activity.

PMID- 25971908
TI  - The rosy future of BCL-2 inhibition in chronic lymphocytic leukemia: pursuit of a
      worthy target.

PMID- 25971909
TI  - A phase I study of thymoglobulin for relapsed or refractory multiple myeloma.

PMID- 25971911
TI  - Using Semantic Similarities and csbl.go for Analyzing Microarray Data.
AB  - Cellular phenotypes result from the combined effect of multiple genes, and high
      throughput techniques such as DNA microarrays and deep sequencing allow
      monitoring this genomic complexity. The large scale of the resulting data,
      however, creates challenges for interpreting results, as primary analysis often
      yields hundreds of genes. Gene Ontology (GO), a controlled vocabulary for gene
      products, enables semantic analysis of such gene sets. GO can be used to define
      semantic similarity between genes, which enables semantic clustering to reduce
      the complexity of a result set. Here, we describe how to compute semantic
      similarities and perform GO-based gene clustering using csbl.go, an R package for
      GO semantic similarity. We demonstrate the approach with expression profiles from
      breast cancer. 

PMID- 25971910
TI  - Normalization of Affymetrix miRNA Microarrays for the Analysis of Cancer Samples.
AB  - microRNA (miRNA) microarray normalization is a critical step for the
      identification of truly differentially expressed miRNAs. This is particularly
      important when dealing with cancer samples that have a global miRNA decrease. In
      this chapter, we provide a simple step-by-step procedure that can be used to
      normalize Affymetrix miRNA microarrays, relying on robust normal-exponential
      background correction with cyclic loess normalization. 

PMID- 25971903
TI  - Information and communication technologies for approaching smokers: a descriptive
      study in primary healthcare.
AB  - BACKGROUND: Common interventions for smoking cessation are based on medical
      advice and pharmacological aid. Information and communication technologies may be
      helpful as interventions by themselves or as complementary tools to quit smoking.
      The objective of the study was to determine the use of information and
      communication technologies (ICTs) in the smoking population attended in primary
      care, and describe the major factors associated with its use. METHODS:
      Descriptive observational study in 84 health centres in Cataluna, Aragon and
      Salamanca. We included by simple random sampling 1725 primary healthcare smokers
      (any amount of tobacco) aged 18-85. Through personal interview professionals
      collected Socio-demographic data and variables related with tobacco consumption
      and ICTs use were collected through face to face interviews Factors associated
      with the use of ICTs were analyzed by logistic regression. RESULTS: Users of at
      least one ICT were predominantly male, young (18-45 years), from most favoured
      social classes and of higher education. Compared with non-ICTs users, users
      declared lower consumption of tobacco, younger onset age, and lower nicotine
      dependence. The percentages of use of email, text messages and web pages were
      65.3%, 74.0% and 71.5%, respectively. Factors associated with the use of ICTs
      were age, social class, educational level and nicotine dependence level. The
      factor most closely associated with the use of all three ICTs was age; mainly
      individuals aged 18-24. CONCLUSIONS: The use of ICTs to quit smoking is
      promising, with the technology of mobile phones having a broader potential.
      Younger and more educated subjects are good targets for ICTs interventions on
      smoking cessation.

PMID- 25971912
TI  - Analysis of microRNA Microarrays in Cardiogenesis.
AB  - microRNAs are a subclass of noncoding RNAs which have been demonstrated to play
      pivotal roles in multiple cellular mechanisms. microRNAs are small RNA molecules
      of 22-24 nt in length capable of modulating protein translation and/or RNA
      stability by base-priming with complementary sequences of the mRNAs, normally at
      the 3'untranslated region. To date, over 2,000 microRNAs have been already
      identified in humans, and orthologous microRNAs have been also identified in
      distinct animals and plants ranging a wide vast of species. High-throughput
      analyses by microarrays have become a gold standard to analyze the changes on
      microRNA expression in normal and pathological cellular or tissue conditions. In
      this chapter, we provide insights into the usage of this uprising technology in
      the context of cardiac development and disease.

PMID- 25971913
TI  - Ontology-Based Analysis of Microarray Data.
AB  - The importance of semantic-based methods and algorithms for the analysis and
      management of biological data is growing for two main reasons. From a biological
      side, knowledge contained in ontologies is more and more accurate and complete,
      from a computational side, recent algorithms are using in a valuable way such
      knowledge. Here we focus on semantic-based management and analysis of protein
      interaction networks referring to all the approaches of analysis of protein
      protein interaction data that uses knowledge encoded into biological ontologies.
      Semantic approaches for studying high-throughput data have been largely used in
      the past to mine genomic and expression data. Recently, the emergence of network
      approaches for investigating molecular machineries has stimulated in a parallel
      way the introduction of semantic-based techniques for analysis and management of
      network data. The application of these computational approaches to the study of
      microarray data can broad the application scenario of them and simultaneously can
      help the understanding of disease development and progress.

PMID- 25971914
TI  - Functional Analysis of microRNA in Multiple Myeloma.
AB  - MicroRNAs (miRNAs) are short non coding RNAs that regulate the gene expression
      and play a relevant role in physiopathological mechanisms such as development,
      proliferation, death, and differentiation of normal and cancer cells. Recently,
      abnormal expression of miRNAs has been reported in most of solid or hematopoietic
      malignancies, including multiple myeloma (MM), where miRNAs have been found
      deeply dysregulated and act as oncogenes or tumor suppressors. Presently, the
      most recognized approach for definition of miRNA portraits is based on microarray
      profiling analysis. We here describe a workflow based on the identification of
      dysregulated miRNAs in plasma cells from MM patients based on Affymetrix
      technology. We describe how it is possible to search miRNA putative targets
      performing whole gene expression profile on MM cell lines transfected with miRNA
      mimics or inhibitors followed by luciferase reporter assay to analyze the
      specific targeting of the 3'untranslated region (UTR) sequence of a mRNA by
      selected miRNAs. These technological approaches are suitable strategies for the
      identification of relevant druggable targets in MM. 

PMID- 25971915
TI  - Directed Myogenic Differentiation of Human Induced Pluripotent Stem Cells.
AB  - Patient-derived induced pluripotent stem cells (iPSCs) have opened the door to
      recreating pathological conditions in vitro using differentiation into diseased
      cells corresponding to each target tissue. Yet for muscular diseases, a method
      for reproducible and efficient myogenic differentiation from human iPSCs is
      required for in vitro modeling. Here, we introduce a myogenic differentiation
      protocol mediated by inducible transcription factor expression that reproducibly
      and efficiently drives human iPSCs into myocytes. Delivering a tetracycline
      inducible, myogenic differentiation 1 (MYOD1) piggyBac (PB) vector to human iPSCs
      enables the derivation of iPSCs that undergo uniform myogenic differentiation in
      a short period of time. This differentiation protocol yields a homogenous
      skeletal muscle cell population, reproducibly reaching efficiencies as high as 70
      90 %. MYOD1-induced myocytes demonstrate characteristics of mature myocytes such
      as cell fusion and cell twitching in response to electric stimulation within 14
      days of differentiation. This differentiation protocol can be applied widely in
      various types of patient-derived human iPSCs and has great prospects in disease
      modeling particularly with inherited diseases that require studies of early
      pathogenesis and drug screening.

PMID- 25971917
TI  - Reduced Density Matrix Functional Theory (RDMFT) and Linear Response Time
      Dependent RDMFT (TD-RDMFT).
AB  - Recent advances in reduced density matrix functional theory (RDMFT) and linear
      response time-dependent reduced density matrix functional theory (TD-RDMFT) are
      reviewed. In particular, we present various approaches to develop approximate
      density matrix functionals which have been employed in RDMFT. We discuss the
      properties and performance of most available density matrix functionals. Progress
      in the development of functionals has been paralleled by formulation of novel
      RDMFT-based methods for predicting properties of molecular systems and solids. We
      give an overview of these methods. The time-dependent extension, TD-RDMFT, is a
      relatively new theory still awaiting practical and generally useful functionals
      which would work within the adiabatic approximation. In this chapter we
      concentrate on the formulation of TD-RDMFT response equations and various
      adiabatic approximations. None of the adiabatic approximations is fully
      satisfactory, so we also discuss a phase-dependent extension to TD-RDMFT
      employing the concept of phase-including-natural-spinorbitals (PINOs). We focus
      on applications of the linear response formulations to two-electron systems, for
      which the (almost) exact functional is known. 

PMID- 25971916
TI  - Chemical Approach to a Whole Body Imaging of Sialo-N-Linked Glycans.
AB  - PET and noninvasive fluorescence imaging of the sialo-N-linked glycan derivatives
      are described. To establish the efficient labeling protocol for N-glycans and/or
      glycoconjugates, new labeling probes of fluorescence and 68Ga-DOTA, as the
      positron emission nucleus for PET, through rapid 6pi-azaelectrocyclization were
      designed and synthesized, (E)-ester aldehydes. The high reactivity of these
      probes enabled the labeling of lysine residues in peptides, proteins, and even
      amino groups on the cell surfaces at very low concentrations of the target
      molecules (~10-8 M) within a short reaction time (~5 min) to result in
      "selective" and "non-destructive" labeling of the more accessible amines. The
      first MicroPET of glycoproteins, 68Ga-DOTA-orosomucoid and asialoorosomucoid,
      successfully visualized the differences in the circulatory residence of
      glycoproteins, in the presence or absence of sialic acids. In vivo dynamics of
      the new N-glycoclusters, prepared by the "self-activating" Huisgen cycloaddition
      reaction, could also be affected significantly by their partial structures at the
      non-reducing end, i.e., the presence or absence of sialic acids, and/or sialoside
      linkages to galactose. Azaelectrocyclization chemistry is also applicable to the
      engineering of the proteins and/or the cell surfaces by the oligosaccharides;
      lymphocytes chemically engineered by sialo-N-glycan successfully target the tumor
      implanted in BALB/C nude mice, detected by noninvasive fluorescence imaging.

PMID- 25971918
TI  - Open fixation of acute anterior glenoid rim fractures with bioresorbable pins:
      analysis of clinical and radiological outcome.
AB  - INTRODUCTION: The purpose of this study was a detailed analysis of clinical and
      radiological results following open fixation of acute-traumatic, displaced
      anterior glenoid rim fractures with bioresorbable pins. MATERIALS AND METHODS:
      This retrospective study included 17 patients with glenoid defect sizes >=20 %,
      as directly measured in preoperative sagittal en face CT. The mean glenoid defect
      size was 25.3 % (20-35, SD 4.7). Two or three polylactid pins were used for
      fixation. Mean age of patients at the time of surgery was 50.1 years (27-71). The
      mean follow-up period was 6.2 years (2.0-11.1). Follow-up included comprehensive
      objective and subjective evaluation of shoulder function as well as standard
      radiographs. RESULTS: The majority of 15/17 patients obtained good or excellent
      clinical results according to the absolute and normalized Constant score, the
      Rowe score, the Oxford shoulder score, the simple shoulder test, the shoulder
      pain and disability index and the subjective shoulder value. Quality of life (SF
      36) showed reference values. Mean or subitem values of all outcome measures did
      not differ from the contralateral, uninjured side. Radiographically, all
      fractures healed without secondary dislocation. Radiological signs of
      glenohumeral arthritis developed in two patients and progressed in two other
      patients. There were no implant-related complications. No patient experienced
      glenohumeral instability or had to undergo revision surgery. CONCLUSIONS:
      Bioresorbable pin fixation is a feasible and safe method of osteosynthesis for
      anterior glenoid rim fractures up to a glenoid defect size of about 35 % and
      enables immediate active range of motion. Good or excellent clinical outcome can
      be expected and glenohumeral stability is reliably restored. The most common mid-
      and long-term complication is occurrence or progression of osteoarthritis. The
      major benefits of bioresorbable pin fixation are redundancy of implant removal,
      minimal risk of implant-related complications and early functional
      rehabilitation.

PMID- 25971919
TI  - Surgical Reconstruction of Maxillary and Mandibular Defects Using a Printed
      Titanium Mesh.
AB  - PURPOSE: To reconstruct maxillary and mandibular defects with printed titanium
      mesh using computer-assisted surgery (CAS) for the achievement of structural,
      esthetic, and functional goals. PATIENTS AND METHODS: The authors designed and
      implemented this prospective study of patients with maxillary or mandibular
      defects who underwent reconstruction with printed titanium mesh using CAS. After
      surgery, the preoperative design and postoperative outcome were evaluated using
      Geomagic Studio software. RESULTS: The sample was comprised of 2 patients with
      maxillary defects and 2 with mandibular defects. A satisfactory contour was
      achieved in all patients. The rate of concordance between the preoperative design
      and the postoperative outcome was higher than 81 and 94% within 3 mm for the
      mandibular and maxillary reconstructions, respectively. CONCLUSION: The results
      of this study suggest that complicated maxillary and mandibular defects can be
      satisfactorily reconstructed with customized printed titanium meshes using CAS.

PMID- 25971920
TI  - Effect of Causative Tooth Extraction on Clinical and Biological Parameters of
      Odontogenic Infection: A Prospective Clinical Trial.
AB  - PURPOSE: To prospectively compare changes of body temperature, white blood cell
      count, fibrinogen, and C-reactive protein between odontogenic infections in which
      the responsible tooth was removed and odontogenic infections in which the
      treatment included no extraction. MATERIALS AND METHODS: The sample was composed
      of patients admitted to the authors' maxillofacial unit for odontogenic infection
      from 2010 through 2013. One hundred seventy-nine patients were categorized into
      an extraction or a non-extraction group based on whether the causative tooth was
      non-restorable or restorable, respectively. Non-restorable teeth were extracted
      at admission of the patient. Otherwise, the treatment protocol, including
      incision of the involved space in conjunction with intravenous antibiotics, was
      the same for the 2 groups. The parameters were measured and recorded at admission
      and 2 days later. Data records were statistically analyzed by comparing the
      change of the parameters studied between the extraction and non-extraction
      groups. P values less than .05 were regarded as statistically significant.
      RESULTS: One hundred seventy-nine patients fulfilled the inclusion criteria and
      were enrolled in the study. The mean age of the patients was 39.1 years (minimum,
      14 yr; maximum, 81 yr; standard deviation, 15.4 yr). One hundred nine patients
      (60.9%) were male, and 70 (39.1%) were female. Differences in the mean decrease
      of axillary temperature, white blood cell count, fibrinogven, and C-reactive
      protein between the 2 groups were 0.178, 2,300, 1.01, and 0.64, respectively. All
      these differences were statistically significant (P =.02, .001, .001, and .001,
      respectively). Also, the mean hospital stay in the extraction group was 1.05 days
      shorter than in the non-extraction group, with the difference being statistically
      significant (P = .006). CONCLUSIONS: In odontogenic maxillofacial infections,
      extraction of the causative tooth is associated with a faster clinical and
      biological resolution of the infection.

PMID- 25971921
TI  - Stereochemistry of amino acid spacers determines the pharmacokinetics of (111)In
      DOTA-minigastrin analogues for targeting the CCK2/gastrin receptor.
AB  - The metabolic instability and high kidney retention of minigastrin (MG) analogues
      hamper their suitability for use in peptide-receptor radionuclide therapy of
      CCK2/gastrin receptor-expressing tumors. High kidney retention has been related
      to N-terminal glutamic acids and can be substantially reduced by coinjection of
      polyglutamic acids or gelofusine. The aim of the present study was to investigate
      the influence of the stereochemistry of the N-terminal amino acid spacer on the
      enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp
      Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met
      Asp-Phe-NH2 ((111)In-PP11-L). Using circular dichroism measurements, we
      demonstrate the important role of secondary structure on the pharmacokinetics of
      the two MG analogues. The higher in vitro serum stability together with the
      improved tumor-to-kidney ratio of the (d-Glu)6 congener indicates that this MG
      analogue might be a good candidate for further clinical study. 

PMID- 25971922
TI  - Precise preoperative localization of prostate cancer employing 12-core needle
      biopsy with a tissue-marking method for effective surgical strategy.
AB  - Prostate needle biopsy plays a pivotal role not only in the diagnosis but also
      the management of patients with prostate cancer. Prostate cancer is often
      multifocal and diagnosis of the lesion could therefore be difficult with
      diagnostic imaging only; thus, multiple core biopsies are taken from several
      different regions of the prostate. In current practice, 10- or 12-core needle
      biopsy is considered the clinical standard. Several techniques have been reported
      to improve the orientation of the specimens, but tissue marking, which could
      theoretically provide important information on the location of the lesion in the
      prostate, has been rarely reported. Therefore, in this study, we evaluated the
      clinical significance of systematic 12-core needle biopsy with tissue marking for
      preoperative prediction of lesion sites and clinicopathological features of
      patients. We evaluated 93 patients who underwent 12-core prostate biopsy and
      subsequent radical prostatectomy. We correlated the biopsy results to the
      prostate sites in which biopsies were performed and prognostic factors of the
      patients, especially the degree of extraprostatic extension (EPE) obtained in
      surgical specimens. Among 253 cancer foci detected in 93 prostatectomy specimens,
      168 (66.4%) foci were detected by biopsy. All patients had proven cancer. EPE
      positive cancers were associated with a larger number of positive cores, larger
      tumor length, and higher percentage of cancer tissue in the corresponding cores.
      Systematic 12-core prostate biopsy with tissue marking is useful for preoperative
      detection of cancer foci and provides valuable information that enables effective
      surgical strategies. 

PMID- 25971924
TI  - Self-organized wrinkling patterns of a liquid crystalline polymer in surface
      wetting confinement.
AB  - Self-organized wrinkling patterns of a liquid crystalline polymer, dictated by
      the chemico-physically anisotropic nature of surface wettability, are
      demonstrated in confined geometries. The symmetry of the geometrical constraints
      of the confinement primarily governs the periodic wrinkling patterns of such a
      polymer in the wetting region. In a circular geometry, the number of the radial
      domains with multi-fold symmetries is linearly proportional to the radius of the
      confinement. The physical origin of the wrinkling process comes from the periodic
      bend-splay distortions through the relaxation of the curvature elasticity. 

PMID- 25971923
TI  - Identification of novel drugs to target dormant micrometastases.
AB  - BACKGROUND: Cancer-specific survival has changed remarkably little over the past
      half century, mainly because metastases that are occult at diagnosis and
      generally resistant to chemotherapy subsequently develop months, years or even
      decades following definitive therapy. Targeting the dormant micrometastases
      responsible for these delayed or occult metastases would represent a major new
      tool in cancer patient management. Our hypothesis is that these metastases
      develop from micrometastatic cells that are suppressed by normal extracellular
      matrix (ECM). METHODS: A new screening method was developed that compared the
      effect of drugs on the proliferation of cells grown on a normal ECM gel (small
      intestine submucosa, SISgel) to cells grown on plastic cell culture plates. The
      desired endpoint was that cells on SISgel were more sensitive than the same cells
      grown as monolayers. Known cancer chemotherapeutic agents show the opposite
      pattern. RESULTS: Screening 13,000 compounds identified two leads with low
      toxicity in mice and EC50 values in the range of 3-30 MUM, depending on the cell
      line, and another two leads that were too toxic to mice to be useful. In a novel
      flank xenograft method of suppressed/dormant cells co-injected with SISgel into
      the flank, the lead compounds significantly eliminated the suppressed cells,
      whereas conventional chemotherapeutics were ineffective. Using a 4T1 triple
      negative breast cancer model, modified for physiological metastatic progression,
      as predicted, both lead compounds reduced the number of large
      micrometastases/macrometastases in the lung. One of the compounds also targeted
      cancer stem cells (CSC) isolated from the parental line. The CSC also retained
      their stemness on SISgel. Mechanistic studies showed a mild, late apoptotic
      response and depending on the compound, a mild arrest either at S or G2/M in the
      cell cycle. CONCLUSIONS: In summary we describe a novel, first in class set of
      compounds that target micrometastatic cells and prevent their reactivation to
      form recurrent tumors/macrometastases.

PMID- 25971925
TI  - The effect of sibutramine prescribing in routine clinical practice on
      cardiovascular outcomes: a cohort study in the United Kingdom.
AB  - BACKGROUND/OBJECTIVES: The marketing authorization for the weight loss drug
      sibutramine was suspended in 2010 following a major trial that showed increased
      rates of non-fatal myocardial infarction and cerebrovascular events in patients
      with pre-existing cardiovascular disease. In routine clinical practice,
      sibutramine was already contraindicated in patients with cardiovascular disease
      and so the relevance of these influential clinical trial findings to the 'real
      World' population of patients receiving or eligible for the drug is questionable.
      We assessed rates of myocardial infarction and cerebrovascular events in a cohort
      of patients prescribed sibutramine or orlistat in the United Kingdom.
      SUBJECTS/METHODS: A cohort of patients prescribed weight loss medication was
      identified within the Clinical Practice Research Datalink. Rates of myocardial
      infarction or cerebrovascular event, and all-cause mortality were compared
      between patients prescribed sibutramine and similar patients prescribed orlistat,
      using both a multivariable Cox proportional hazard model, and propensity score
      adjusted model. Possible effect modification by pre-existing cardiovascular
      disease and cardiovascular risk factors was assessed. RESULTS: Patients
      prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial
      infarction or cerebrovascular events compared with those taking orlistat
      (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However,
      subgroup analysis showed the elevated rate was larger in those with pre-existing
      cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64),
      compared with those with no cardiovascular disease (hazard ratio 1.52, 95%
      confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not
      increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence
      interval 0.34-1.32). CONCLUSIONS: Sibutramine was associated with increased rates
      of acute cardiovascular events in people with pre-existing cardiovascular
      disease, but there was a low absolute risk in those without. Sibutramine's
      marketing authorization may have, therefore, been inappropriately withdrawn for
      people without cardiovascular disease.

PMID- 25971926
TI  - Maternal obesity programs offspring non-alcoholic fatty liver disease through
      disruption of 24-h rhythms in mice.
AB  - BACKGROUND: Maternal obesity increases offspring propensity to metabolic
      dysfunctions and to non-alcoholic fatty liver disease (NAFLD), which may lead to
      cirrhosis or liver cancer. The circadian clock is a transcriptional/epigenetic
      molecular machinery synchronising physiological processes to coordinate energy
      utilisation within a 24-h light/dark period. Alterations in rhythmicity have
      profound effects on metabolic pathways, which we sought to investigate in
      offspring with programmed NAFLD. METHODS: Mice were fed a standard or an
      obesogenic diet (OD), before and throughout pregnancy, and during lactation.
      Offspring were weaned onto standard or an OD at 3 weeks postpartum and housed in
      12:12 light/dark conditions. Biochemical and histological indicators of NAFLD and
      fibrosis, analysis of canonical clock genes with methylation status and locomotor
      activity were investigated at 6 months. RESULTS: We show that maternal obesity
      interacts with an obesogenic post-weaning diet to promote the development of
      NAFLD with disruption of canonical metabolic rhythmicity gene expression in the
      liver. We demonstrate hypermethylation of BMAL-1 (brain and muscle Arnt like-1)
      and Per2 promoter regions and altered 24-h rhythmicity of hepatic pro
      inflammatory and fibrogenic mediators. CONCLUSIONS: These data implicate
      disordered circadian rhythms in NAFLD and suggest that disruption of this system
      during critical developmental periods may be responsible for the onset of chronic
      liver disease in adulthood.

PMID- 25971928
TI  - Cerebral activations during viewing of food stimuli in adult patients with
      acquired structural hypothalamic damage: a functional neuroimaging study.
AB  - BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to
      tumours. Homeostatic and non-homeostatic brain centres control appetite and
      energy balance but their interaction in the presence of hypothalamic damage
      remains unknown. We hypothesized that abnormal appetite in obese patients with
      hypothalamic damage results from aberrant brain processing of food stimuli. We
      sought to establish differences in activation of brain food motivation and reward
      neurocircuitry in patients with hypothalamic obesity (HO) compared with patients
      with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a
      cross-sectional study at a University Clinical Research Centre, we studied 9
      patients with HO, 10 age-matched obese controls, 7 patients who remained weight
      stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional
      magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a
      test meal, while subjects were presented with images of high-calorie foods, low
      calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY
      and ghrelin were measured throughout the experiment, and appetite ratings were
      recorded. RESULTS: Mean neural activation in the posterior insula and lingual
      gyrus (brain areas linked to food motivation and reward value of food) in HWS
      were significantly lower than in the other three groups (P=0.001). A significant
      negative correlation was found between insulin levels and posterior insula
      activation (P=0.002). CONCLUSIONS: Neural pathways associated with food
      motivation and reward-related behaviour, and the influence of insulin on their
      activation may be involved in the pathophysiology of HO.

PMID- 25971930
TI  - Quantitative microscopy of mole rat eosinophil granule morphology.
AB  - Mole rat bone marrow cells and peritoneal eosinophils are used to study granule
      morphological maturation by quantitative microscopy. The bulk eosinophil granule
      content is pre-stored in unique granular structures known as crystalloid or
      secondary granules. Mole rat eosinophil granules exhibit the basic structure of
      an electron-dense crystalloid core surrounded by a lighter, homogeneous matrix.
      Morphometric analysis demonstrated that bone marrow-derived eosinophil sphere
      like granules display a periodic, multimodal granule volume distribution. In
      contrast, peritoneal eosinophils display cigar-shaped granules, whose crystalloid
      cores are more variable in size and shape as compared to bone marrow eosinophil
      granules. Using a morphometric approach, we deduced that the basic granule volume
      quantum is similar in both cases, suggesting that the sphere-like young
      eosinophil granules turn into dense ellipsoidal ones by intragranular processes
      in which both volume and membrane surface are conserved. Crystalloid granule
      mediators are known to be widely associated with allergic inflammatory events,
      which may damage the host tissue following secretion to the extracellular
      environment. Based on mathematical modeling, we suggest that this deviation from
      sphere-like to ellipsoidal shape reflects an adaptive response of the mole rat to
      its unique solitary life. 

PMID- 25971929
TI  - Anastrozole is a dose-specific superovulator and favors implantation in rats: a
      prospective study.
AB  - An alternative superovulator to replace clomiphene citrate (CC) is needed as it
      is unsuitable for women with polycystic ovarian syndrome and is associated with
      low pregnancy rates. Anastrozole is an effective superovulator, but has not been
      well researched. The aim of this study was to determine the optimal dose of
      anastrozole as a superovulator and ascertain its effects on implantation and
      uterine ultrastructure during early pregnancy in Wistar rats using scanning
      electron microscopy. The uterine morphological characteristics which were studied
      in day 1 and 6 pregnant rats include microvilli density, length, surface "beads",
      surface glycocalyx, cell borders and apices, uterine surface fording and large
      surface protrusions. A significant increase in implantation sites is seen in the
      15 mg/kg anastrozole group, compared to control. Day 1 and 6 anastrozole groups
      have similar morphology to the control and different to the CC group. At day 6,
      large surface protrusions are mostly noted but not limited to anastrozole-treated
      rats; anastrozole also appears to retain glycocalyx to some extent. The increased
      number of implantation sites in the 15 mg/kg anastrozole group suggests that this
      dose superovulates and favors implantation. Anastrozole is probably dose-/species
      specific and additionally the surface uterine morphology suggests that
      anastrozole is implantation friendly. 

PMID- 25971931
TI  - Epigallocatechin-3-gallate-induced free-radical production upon adipogenic
      differentiation in bovine bone-marrow mesenchymal stem cells.
AB  - Epigallocatechin-3-gallate (EGCG), a major component of catechin in green tea,
      has known effects on cancer, diabetes and obesity. We recently reported that the
      expression levels of various genes and proteins involved in adipogenesis
      decreases following EGCG treatment. We also assessed apoptosis in EGCG-exposed
      cells. Here, we explore the variability in free-radical production in bovine bone
      marrow mesenchymal stem cells (BMSCs) treated with EGCG. Upon adipogenic
      differentiation, BMSCs were exposed to various EGCG concentrations (0, 0.1, 1, 5,
      or 10 MUM) for 2, 4, or 6 days. We found that EGCG reduced cell viability and
      arrested the cell cycle at the gap 2/mitosis phase and that EGCG potentially
      enhanced the production of free radicals, including reactive oxygen species and
      reactive nitrogen species, in a concentration- and time-dependent manner.
      Immunostaining revealed that the expression of genes encoding CCAAT/enhancer
      binding protein alpha and stearoyl-CoA desaturase were diminished by EGCG
      treatment. These findings suggest that EGCG alters free-radical production
      activity during adipogenic differentiation in BMSCs. 

PMID- 25971927
TI  - The role of short chain fatty acids in appetite regulation and energy
      homeostasis.
AB  - Over the last 20 years there has been an increasing interest in the influence of
      the gastrointestinal tract on appetite regulation. Much of the focus has been on
      the neuronal and hormonal relationship between the gastrointestinal tract and the
      brain. There is now mounting evidence that the colonic microbiota and their
      metabolic activity have a significant role in energy homeostasis. The supply of
      substrate to the colonic microbiota has a major impact on the microbial
      population and the metabolites they produce, particularly short chain fatty acids
      (SCFAs). SCFAs are produced when non-digestible carbohydrates, namely dietary
      fibres and resistant starch, undergo fermentation by the colonic microbiota. Both
      the consumption of fermentable carbohydrates and the administration of SCFAs have
      been reported to result in a wide range of health benefits including improvements
      in body composition, glucose homeostasis, blood lipid profiles and reduced body
      weight and colon cancer risk. However, published studies tend to report the
      effects that fermentable carbohydrates and SCFAs have on specific tissues and
      metabolic processes, and fail to explain how these local effects translate into
      systemic effects and the mitigation of disease risk. Moreover, studies tend to
      investigate SCFAs collectively and neglect to report the effects associated with
      individual SCFAs. Here, we bring together the recent evidence and suggest an
      overarching model for the effects of SCFAs on one of their beneficial aspects:
      appetite regulation and energy homeostasis. 

PMID- 25971932
TI  - Neuroanatomy of pars intercerebralis neurons with special reference to their
      connections with neurons immunoreactive for pigment-dispersing factor in the blow
      fly Protophormia terraenovae.
AB  - Input regions of pars intercerebralis (PI) neurons are examined by confocal and
      electron microscopies with special reference to their connections with neurons
      immunoreactive for pigment-dispersing factor (PDF) in the blow fly, Protophormia
      terraenovae. PI neurons are a prerequisite for ovarian development under long-day
      conditions. Backfills from the cardiac recurrent nerve after severance of the
      posterior lateral tracts labeled thin fibers derived from the PI neurons in the
      superior medial protocerebrum. These PI fibers were mainly synapsin-negative and
      postsynaptic to unknown varicose profiles containing dense-core vesicles.
      Backfilled fibers in the periesophageal neuropils, derived from the PI neurons or
      neurons with somata in the subesophageal zone, were varicose and some were
      synapsin-positive. Electron microscopy revealed the presence of both presynaptic
      and postsynaptic sites in backfilled fibers in the periesophageal neuropils. Many
      PDF-immunoreactive varicosities were found in the superior medial and lateral
      protocerebrum and double-labeling showed that 60-88 % of PDF-immunoreactive
      varicosities were also synapsin-immunoreactive. Double-labeling with the
      backfills and PDF immunocytochemistry showed that the PI fibers and PDF
      immunoreactive varicosities were located close to each other in the superior
      medial protocerebrum. Results of triple-labeling of PI neurons, PDF
      immunoreactive neurons and synapsin-immunoreactive terminals demonstrated that
      the synapsin-positive PDF-immunoreactive varicosities contacted the PI fibers.
      These data suggest that PI neurons receive synaptic contacts from PDF
      immunoreactive fibers, which are derived from circadian clock neurons, of small
      ventral lateral neurons (previously called OL2) or posterior dorsal (PD) neurons
      with somata in the pars lateralis. 

PMID- 25971933
TI  - The dendrimer paradox--high medical expectations but poor clinical translation.
AB  - This review was written with the intention to critically evaluate the status of
      dendrimers as drug carriers and find answers as to why this class of compounds
      has not translated into the clinic despite 40 years of research. Topics addressed
      and challenged are the current state of dendrimer synthesis, for example the
      importance for surface multifunctionality and internal functional groups. Large
      numbers of surface groups are deemed one of the advantages of dendrimers;
      however, only small amounts of drugs can be conjugated to the surface without
      altering the dendrimer's performance, for example its solubility. On the other
      hand, the rarely utilized feature of internal functionalities for drug
      conjugation would allow drug loading without altering the surface composition and
      therefore lead to improved carrier-to-active weight ratios, a major concern for
      industrial drug product development. Synthetic approaches resulting in truly
      multifunctional nanocarriers based on chemical conjugation are being discussed,
      involving orthogonal and 'click' chemistries. Random conjugation of drug, imaging
      agent, and targeting ligand to the surface of pre-existing dendrimers results in
      poorly-defined compound mixtures that are unlikely to pass regulatory revision
      and translate into the clinic. Similarly, using dendrimers for physical drug
      entrapment is an approach with little clinical future because alternative, low
      cost carriers are available and have translated to the market. Finally, a case is
      being made to evaluate other dendritic polymers such as dendrons, dendrigrafts,
      hyperbranched polymers, and dendronized polymers for delivery applications. Non
      spherical shapes and structural flexibility are features generally discussed in
      vector-based drug delivery applications and therefore criteria worthwhile to
      evaluate. 

PMID- 25971934
TI  - Evaluation of the Bruker Matrix-Assisted Laser Desorption-Ionization Time-of
      Flight Mass Spectrometry (MALDI-TOF MS) System for the Identification of
      Clinically Important Dermatophyte Species.
AB  - Dermatophytes can invade the stratum corneum of the skin and other keratinized
      tissues and are responsible for a broad diversity of diseases of skin, nails and
      hair. Although the standard identification of dermatophytoses depends on
      macroscopic and microscopic characterization of the colonies grown on special
      media, there are a number of limitations owing to intraspecies morphological
      variability, atypical morphology or interspecies morphological similarity which
      entails improvement in the identification methods. Matrix-assisted laser
      desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a novel
      method which proved to be effective for rapid and reliable identification of
      dermatophytes grown in cultures when compared to conventional methods. We
      evaluated the performance of Bruker MALDI-TOF MS System (Bruker Daltonics,
      Germany) for identification of clinically relevant dermatophytes. In order to
      increase the identification capacity of the system, we created supplemental
      spectral database entries using ten reference dermatophyte strains (ten species
      in two genera). The utility of the generated database was then challenged using a
      total of 126 dermatophytes (115 clinical isolates and 11 additional reference
      strains). The results were evaluated by both manufacturer-recommended and lowered
      cutoff scores. MALDI-TOF MS provided correct identification in 122 (96.8 %) and
      113 (89.7 %) of the isolates with the lowered scores and using the supplemented
      database, respectively, versus 65 (51.6 %) and 17 (13.5 %) correct
      identifications obtained by the unmodified database and recommended scores at the
      genus and species levels, respectively. Our results support the potential utility
      of MALDI-TOF MS as a routine tool for accurate and reliable identification of
      dermatophytes.

PMID- 25971935
TI  - Biomarkers of inflammation in persons with chronic tetraplegia.
AB  - In addition to lung volume restriction, individuals with chronic tetraplegia
      exhibit reduced airway caliber and bronchodilator responsiveness similar to
      persons with asthma. In asthma, airflow obstruction is closely linked to airway
      inflammation. Conversely, little is known regarding the airway inflammatory
      response in tetraplegia. To compare levels of biomarkers of inflammation in
      exhaled breath condensate (EBC) and serum in subjects with chronic tetraplegia,
      mild asthma, and able-bodied controls.Prospective, observational pilot study.
      Thirty-four subjects participated: tetraplegia (n = 12), asthma (n = 12),
      controls (n = 10). Biomarkers in EBC [8-isoprostane (8-IP), leukotriene B4 (LT
      B4), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TNF-alpha),
      interleukin 6 (IL-6)] and serum (8-IP, LT-B4, TNF-alpha, IL-6) were determined
      using commercially available EIA kits (Cayman Chemical Company, Ann Arbor, MI).
      Separate, one-way ANOVA with Bonferroni's post-hoc analyses were performed to
      determine group differences in demographic and dependent variables [EBC and serum
      biomarkers, fractional exhaled nitric oxide (FeNO), pulmonary function
      parameters, and specific airway conductance (sGaw)]. The tetraplegia group had
      significantly elevated 8-IP levels in EBC compared to the asthma (68 +/- 38
      versus 21 +/- 13 pg ml(-1); p < 0.001) and control groups (22 +/- 13 pg ml(-1); p
      < 0.01), respectively. FeNO levels were significantly elevated in the asthma
      compared to the control group (26 +/- 18 versus 11 +/- 4 ppb; p < 0.05), and
      trended higher than levels in the tetraplegia group (15 +/- 6; p = 0.08). Levels
      of serum biomarkers did not differ significantly among groups. Through analysis
      of EBC, levels of 8-IP were significantly elevated compared to levels found in
      individuals with mild asthma and healthy controls. Further studies are needed to
      extend upon these preliminary findings that suggest the presence of airway
      inflammation in subjects with chronic tetraplegia, and how this relates to
      pulmonary dysfunction in this population.

PMID- 25971936
TI  - No Significant Increase in the Delta4- and Delta7-Dafachronic Acid Concentration
      in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.
AB  - The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan
      in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However,
      little is known about how DA concentrations change under various physiologic
      conditions and about how DA/DAF-12 signaling interacts with other signaling
      pathways that also regulate dauer formation and lifespan. Using a sensitive
      bioanalytical method, we quantified the endogenous DA concentrations in a long
      lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d)
      mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in
      the glp-1 mutant was similar to that in the wild type (WT). This result is
      contrary to the long-held belief that germline loss-induced longevity involves
      increased DA production and suggests instead that this type of longevity involves
      an enhanced response to DA. We also found evidence suggesting that increased DA
      sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3
      stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT
      level. This finding is consistent with the previously proposed positive feedback
      regulation between DAF-12 and DA production. Surprisingly, the DA concentrations
      in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the
      L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf
      c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental
      evidence suggested that the positive feedback between DA and DAF-12 was partially
      induced in the three Daf-d mutants. 

PMID- 25971937
TI  - Targeting Mesothelin with Modified T Cells.

PMID- 25971940
TI  - First principles potential for the cytosine dimer.
AB  - We developed a new first principles potential for the cytosine dimer. The ab
      initio calculations were performed with a DFT-SAPT combination of the symmetry
      adapted perturbation method and density functional theory, and fitted to a model
      site-site functional form. The model potential was used to predict cluster
      structures up to cytosine hexamers. The global cluster structure optimizations
      showed that the new potential is able to reproduce some of the 2D filament
      structures. Moreover many new non-planar cytosine cluster structures were also
      discovered. Interaction energies of these clusters were compared with B3LYP-D,
      MP2, SCS-MP2, SCS-MI-MP2 and AMBER. It has been shown that the model agrees well
      with all ab initio methods, especially for the cytosine hexamer. The model
      potential outperforms the AMBER force field and therefore it can be exploited to
      study more challenging larger systems. 

PMID- 25971938
TI  - Activation of MET via diverse exon 14 splicing alterations occurs in multiple
      tumor types and confers clinical sensitivity to MET inhibitors.
AB  - Focal amplification and activating point mutation of the MET gene are well
      characterized oncogenic drivers that confer susceptibility to targeted MET
      inhibitors. Recurrent somatic splice site alterations at MET exon 14 (METex14)
      that result in exon skipping and MET activation have been characterized, but
      their full diversity and prevalence across tumor types are unknown. Here, we
      report analysis of tumor genomic profiles from 38,028 patients to identify 221
      cases with METex14 mutations (0.6%), including 126 distinct sequence variants.
      METex14 mutations are detected most frequently in lung adenocarcinoma (3%), but
      also frequently in other lung neoplasms (2.3%), brain glioma (0.4%), and tumors
      of unknown primary origin (0.4%). Further in vitro studies demonstrate
      sensitivity to MET inhibitors in cells harboring METex14 alterations. We also
      report three new patient cases with METex14 alterations in lung or histiocytic
      sarcoma tumors that showed durable response to two different MET-targeted
      therapies. The diversity of METex14 mutations indicates that diagnostic testing
      via comprehensive genomic profiling is necessary for detection in a clinical
      setting. SIGNIFICANCE: Here we report the identification of diverse exon 14
      splice site alterations in MET that result in constitutive activity of this
      receptor and oncogenic transformation in vitro. Patients whose tumors harbored
      these alterations derived meaningful clinical benefit from MET inhibitors.
      Collectively, these data support the role of METex14 alterations as drivers of
      tumorigenesis, and identify a unique subset of patients likely to derive benefit
      from MET inhibitors.

PMID- 25971941
TI  - Palladium-catalyzed aerobic oxidative double allylic C-H oxygenation of alkenes:
      a novel and straightforward route to alpha,beta-unsaturated esters.
AB  - A mild tandem oxidative functionalization of allyl aromatic hydrocarbons was
      accomplished using the catalytic system of Pd(OAc)2/DMA under 1 atm O2. The green
      twofold C-O bond formation involving double allylic C-H oxygenation unlocks
      opportunities for markedly different synthetic strategies. Moreover, the reaction
      affords aryl alpha,beta-unsaturated esters directly from readily available
      terminal olefins in moderate to good yields with excellent chemo- and
      stereoselectivities. 

PMID- 25971939
TI  - Response to MET inhibitors in patients with stage IV lung adenocarcinomas
      harboring MET mutations causing exon 14 skipping.
AB  - Mutations in the MET exon 14 RNA splice acceptor and donor sites, which lead to
      exon skipping, deletion of the juxtamembrane domain containing the CBL E3
      ubiquitin ligase-binding site, and decreased turnover of the resultant aberrant
      MET protein, were previously reported to be oncogenic in preclinical models. We
      now report responses to the MET inhibitors crizotinib and cabozantinib in four
      patients with stage IV lung adenocarcinomas harboring mutations leading to MET
      exon 14 skipping, highlighting a new therapeutic strategy for the 4% of lung
      adenocarcinoma patients whose tumors harbor this previously underappreciated
      genetic alteration. SIGNIFICANCE: Oncogenic mutations in the MET exon 14 splice
      sites that cause exon 14 skipping occur in 4% of lung adenocarcinomas. We report
      responses to the MET inhibitors crizotinib and cabozantinib in patients with lung
      adenocarcinomas harboring MET exon 14 splice site mutations, identifying a new
      potential therapeutic target in this disease.

PMID- 25971943
TI  - Vaccination Exemption and the Pediatric Health Care Provider.

PMID- 25971942
TI  - Influence of Free Amino Acids, Oligopeptides, and Polypeptides on the Formation
      of Pyrazines in Maillard Model Systems.
AB  - Pyrazines are specific Maillard reaction compounds known to contribute to the
      unique aroma of many products. Most studies concerning the generation of
      pyrazines in the Maillard reaction have focused on amino acids, while little
      information is available on the impact of peptides and proteins. The present
      study investigated the generation of pyrazines in model systems containing whey
      protein, hydrolyzed whey protein, amino acids, and glucose. The impact of thermal
      conditions, ratio of reagents, and water activity (a(w)) on pyrazine formation
      was measured by headspace solid-phase microextraction with gas
      chromatography/mass spectrometry (HS-SPME-GC/MS. The presence of oligopeptides
      from hydrolyzed whey protein contributed significantly to an increased amount of
      pyrazines, while in contrast free amino acids generated during protein hydrolysis
      contributed to a lesser extent. The generation of pyrazines was enhanced at low
      a(w) (0.33) and high temperatures (>120  degrees C). This study showed that the
      role of peptides in the generation of pyrazines in Maillard reaction systems has
      been dramatically underestimated.

PMID- 25971944
TI  - Case series and review of glandular odontogenic cyst with emphasis on treatment
      modalities.
AB  - Glandular odontogenic cyst is a newly determined jaw entity with aggressive
      behavior and a high rate of recurrence. There is histopathologic resemblance to
      other lesions of the jaw such as intraosseous mucoepidermoid carcinoma. Although
      enucleation and curettage are not the treatment of choice for this cystic lesion,
      they comprise the most common method. On the other hand, filling the defect is a
      controversial matter, especially in lesions with large size. We introduce 4 cases
      of GOC, of which 2 are cases of recurrence. We applied bone material substitutes
      in 3 of these cases with success. 

PMID- 25971945
TI  - Renewable sorbent material for solid phase extraction with direct coupling of
      sequential injection analysis-bead injection to liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - The use of small scale renewable sorbent material for automated solid phase
      extraction of multi-residue pharmaceuticals in environmental samples exploiting
      the sequential injection analysis-bead injection with direct coupling to liquid
      chromatography-electrospray ionization tandem mass spectrometry (SIA-BI-MUSPE-LC
      ESI-MS/MS) is presented to determine beta-blockers, namely atenolol, sotalol,
      pindolol, acebutolol, timolol, metoprolol, labetalol, carazolol, propranolol and
      betaxolol. These compounds yielded the same product ions, therefore were affected
      in terms of quantification when flow injection analysis-mass spectrometry (FIA
      MS) was used. Thus, analytes and matrix present in the sample travel together
      into the ionization source which can seriously affect the ionization efficiency
      and analyte signals due to monitoring over a short time period. Graphical
      abstract A two-dimensional analysis involving a time dimension (retention time)
      and an m/z dimension (fragmentation ion) is promising for the various sample
      types. Using the developed method, absolute recoveries percentages of 10 mL of
      sample loading volume were >91% for all beta-blockers with enrichment factor of
      62-74, limits of detection of 0.005-0.07 MUg L(-1), limits of quantification of
      0.01-0.23 MUg L(-1), enrichment factor of 62-72 and repeatability within range 7
      12%. This developed method is suggested to be used as quantitative screening
      technique for drugs of abuse or persistent contamination using different kinds of
      sorbent materials and complex matrix such as biological fluid sample as well.

PMID- 25971946
TI  - Effect of dietary methionine content on growth performance, carcass traits, and
      feather growth of Pekin duck from 15 to 35 days of age.
AB  - A study was conducted to establish the response of Pekin ducks to dietary Met
      from 15 to 35 d age. Experimental diets were formulated to contain 0.35, 0.45,
      0.55, 0.65, and 0.75% Met (0.30, 0.39, 0.45, 0.56, and 0.68% on an analyzed
      basis, respectively) and 0.3% cysteine (0.25, 0.27, 0.26, 0.26, and 0.28% on an
      analyzed basis, respectively). Each diet was fed to 10 pens of 55 ducks/pen.
      Carcass yields and feather growth were determined at 28 and 35 d. Results showed
      that feeding 0.30% Met (0.55% Met+Cys) significantly impaired ADG, feed-to-gain
      (F:G) ratio, breast meat yield, and feather growth in comparison to the other
      dietary treatments (P < 0.05). BW, ADG, F: G, carcass and breast meat weight and
      yield, breast skin and subcutaneous fat weight and yield, the fourth primary wing
      feather length, and feather coverage showed significant quadratic broken-line or
      quadratic polynomial response to increasing dietary Met (P < 0.05). From 15 to 28
      d age, the optimal Met requirement for the BW, breast meat yield, and the fourth
      primary wing feather length were 0.510, 0.445, and 0.404%, respectively, based on
      quadratic broken-line model, and correspondingly were 0.606, 0.576, and 0.559% by
      quadratic regression. For ducks from 15 to 35 d age, the optimal Met requirement
      for BW, breast meat yield, and feather coverage were 0.468, 0.408, and 0.484%,
      respectively, by quadratic broken-line model, and 0.605, 0.564, and 0.612%, by
      quadratic regression, respectively.

PMID- 25971947
TI  - Relationship between wheat characteristics and nutrient digestibility in
      broilers: comparison between total collection and marker (titanium dioxide)
      technique.
AB  - Three wheat cultivars (Orpheus, Rustic, and Viscount) were used to formulate 3
      test feeds (62.4% wheat) in a broiler digestibility trial. The diets were fed to
      male Ross 308 broiler chickens. The wheat cultivars mainly differed in their
      amount of non-starch polysaccharides ( NSP: ). The cultivar Orpheus was chosen to
      represent a high amount of NSP (102 g/kg DM), whereas the cultivars Rustic and
      Viscount represented low amounts of NSP (83.4 g/kg DM and 73.9 g/kg DM,
      respectively). Furthermore, the cultivars Orpheus and Viscount were feed quality
      wheat, whereas Rustic was a milling quality wheat. Nutrient digestibilities and
      AMEn contents of the diets were measured from 18 to 22-days-old by total excreta
      collection, or with the use of the indigestible marker titanium dioxide. In
      addition, the ileal viscosity was measured when the broilers were 25-days-old.
      Wheat cultivar affected N retention, DM digestibility, and AMEn. In general, the
      feed formulated with the high NSP wheat cultivar Orpheus resulted in the least
      favorable nutrient digestibilities and AMEn, whereas the results were better when
      the feed was formulated with the low NSP cultivars Viscount and Rustic. Feeding
      the Rustic cultivar caused the highest intestinal viscosity, although this was
      not reflected in the animal responses. Nutrient digestibilities and AMEn content
      of the diets were lower when calculated with the titanium dioxide marker than
      with the total excreta collection procedure. Moreover, the P-values of the effect
      of wheat cultivar on DM digestibility, N retention, crude fat digestibility and
      AMEn were lower with the use of the titanium dioxide marker. It can be concluded
      that wheat cultivar affected nutrient digestibility and AMEn, and that the
      observed differences were related to the amount of NSP. Furthermore, both the
      titanium dioxide marker and the total excreta collection methods showed the same
      trends despite the different values obtained. The titanium dioxide marker method
      was the simplest to use and produced valid results. 

PMID- 25971948
TI  - Evaluation of inclusion level of wheat distillers dried grains with solubles with
      and without protease or beta-mannanase on performance and water intake of turkey
      hens.
AB  - It is becoming a common practice to use higher levels of wheat distillers dried
      grains with solubles (wDDGS) in poultry diets. The objective of this study was to
      determine the effects of level of inclusion of wDDGS with or without enzyme (E-,
      i.e., wDDGSE-) supplementation on performance and water consumption of turkey
      hens (0 to 72 d). Two diets (0 or 30% wDDGS) were formulated to meet the nutrient
      requirements of Hybrid Converter turkeys. Diets (0 or 30% wDDGS; starter, grower,
      and finisher) were then blended to obtain a different level of inclusion (15%) of
      wDDGS. The 30% wDDGS diet was divided into 3 fractions and 2 fractions
      supplemented with either protease (P+, i.e., wDDGSP+; 0.126 g/kg) or beta
      mannanase (M+, i.e., wDDGSM+; 0.05 g/kg). All 5 diets were fed ad libitum as
      mash. The 700 0-d turkey hens were randomly allocated into groups of 35 birds per
      replicate with 4 replicate floor pens per treatment, in a completely randomized
      design. Water consumption per pen was recorded beginning at 7 d. There was no
      effect of dietary treatment on feed intake. BW of turkey hens (52 d; grower) was
      significantly higher for 30% wDDGSP+ as compared to 0% wDDGSE- or 15% wDDGSE-
      diets; but was not different from 30% wDDGSE- or 30% wDDGSM+ diets. FCR (P <
      0.01; 28 to 52 d), and total FCR (P < 0.05; 0 to 72 d) was significantly improved
      for birds fed 15 or 30% wDDGS regardless of enzyme treatment compared to 0%
      wDDGSE-. Water intake (WI, in mL per bird per day) tended to be higher (P = 0.08)
      between 7 and 28 d for 30% wDDGSP+ diets compared to other treatments. Similarly,
      WI of birds fed 30% wDDGSP+ was higher (P < 0.05; 28 to 52 and 52 to 72 d) and
      total WI (P = 0.07; 7 to 72 d) tended to be higher than other treatments. This
      study is the first to report the impact of wDDGS on WI. As high as 30% wDDGS can
      be substituted in turkey hen diets. No effect of P+ or M+ at the inclusion level
      tested was found on performance. 

PMID- 25971949
TI  - Effects of preincubation application of low and high frequency ultrasound on
      eggshell microbial activity, hatchability, supply organ weights at hatch, and
      chick performance in Japanese quail (Coturnix coturnix japonica) hatching eggs.
AB  - The aim of the current study was to establish the effects of preincubation
      application of low and high frequency ultrasound on egg weight loss,
      hatchability, supply organ weights, chick performance, and eggshell microbial
      activity in Japanese quail (Coturnix coturnix japonica). A total of 630 fresh
      eggs were randomly divided into 3 groups. Treatments were no ultrasound but eggs
      were sprayed with benzalkonium chloride solution (B), 35 kHz ultrasound applied
      for 30 min (U35), and 130 kHz ultrasound applied for 30 min (U130). At the
      beginning of the incubation, the eggs in the U130 treatment had lower coliform,
      Salmonella, and Staphylococcus counts than those in the B group. However, no
      significant differences were found in coliform, Salmonella, and Staphylococcus
      counts among treatments at d 14 of incubation. Among treatments, there were no
      significant differences in egg weight loss, hatchability, embryonic mortality,
      supply organ weights, spread of hatch, or relative growth.

PMID- 25971950
TI  - A survey of Mycoplasma gallisepticum and Mycoplasma synovaie with avian influenza
      H9 subtype in meat-type chicken in Jordan between 2011-2015.
AB  - Commercial chickens in Jordan suffer from respiratory disease of undetermined
      etiology. This study was designed to document the involvement of avian influenza
      virus (AIV) H9 subtype, Mycoplasma gallisepticum (MG), and Mycoplasma synoviae
      (MS) in this respiratory disease. In this study, trachea swabs from 350
      commercial broiler chicken flocks that suffered from respiratory disease were
      tested for AIV H9 subtype by using reverse transcription (RT)-PCR and for MG and
      MS by using PCR. PCR and RT-PCR results showed that 23.7, 8.9, and 6.6% of these
      flocks were infected with AIV H9 subtype, MS, and MG, respectively, whereas 12.9
      and 5.7% of these flocks were infected with both AIV H9 subtype and MS and AIV H9
      subtype and MS, respectively. Furthermore, 42.3% of these flocks were negative
      for the above mentioned respiratory diseases. Further epidemiological studies are
      recommended to determine risk factors and evaluate the economic consequences of
      AIV H9 subtype, MG, and MS infections in the region. Furthermore, studies are
      required to isolate AIV H9 subtype, MG, and MS and develop vaccines against the
      local field isolates. 

PMID- 25971951
TI  - [Data protection, radiation protection and copyright: Problems of transferring
      results in assessment practice].
AB  - In Germany, the medical assessor is subject to the law on contracts for work and
      services ("Werksvertragsrecht"). When a medical expert assesses a subject on
      behalf of a third party, there is no contractual relationship between them. In
      the field of private insurance law and in social insurance law, the medical
      expert is faced with various procedural requirements. Failing to meet these legal
      requirements often makes the assessment difficult or even impossible. The
      transfer of radiographs to the medical assessor is dealt with in the German X-ray
      regulations ("Rontgenverordnung"). The assessor, who is without doubt an
      examining doctor, has the right to have the radiographs temporarily made
      available (S 28 et al.). Passing on the radiographs is all the more appropriate
      if by doing so additional X-ray examinations can be avoided. The right of access
      to medical data in the social security law, apart from X-ray regulations, is
      regulated by German Civil Code (BGB) S 810 and German Basic Law section 1
      paragraph 1 in connection with section 2 paragraph 1 ("S 810 BGB; Art. 1 Abs. 1,
      Art. 2 Abs. 1 GG"). In the absence of third party interest worthy of protection,
      the right of access to assessment records has to be granted to the subject, who
      will then authorize the examining medical expert to exercise this right. In
      private insurance law, only the private health insurance has its regulation
      concerning obtaining information about treatment or the access to medical
      assessments. In other types of insurance the medical assessor's right of access
      to medical examination data and/or the basis for medical findings can only be
      derived from secondary obligations as part of the insurance contract or directly
      from general constitutional personal rights.

PMID- 25971952
TI  - Phosphodiesterase 8B and cyclic AMP signaling in the adrenal cortex.
AB  - Bilateral adrenocortical hyperplasia (BAH) in humans and mice has been recently
      linked to phosphodiesterase (PDE) 8B (PDE8B) and 11 (PDE11A) defects. These
      findings have followed the discovery that defects of primary genes of the cyclic
      monophosphatase (cAMP) signaling pathway, such as guanine nucleotide binding
      alpha subunit and PRKAR1A, are involved in the pathogenesis of BAH in humans;
      complete absence of Prkar1a in the adrenal cortex of mice also led to pathology
      that mimicked the human disease. Here, we review the most recent findings in
      human and mouse studies on PDE8B, a cAMP-specific PDE that appears to be highly
      expressed in the adrenal cortex and whose deficiency may underlie predisposition
      to BAH and possibly other human diseases.

PMID- 25971953
TI  - Does influenza vaccination influence cardiovascular complications?
AB  - Each year, influenza infection is responsible for substantial morbidity and
      mortality across the globe. Because confirmatory testing is often not performed,
      the total burden of influenza on annual cardiopulmonary (respiratory and cardiac)
      hospitalizations is likely even higher. 

PMID- 25971954
TI  - Oxocentered Cu(II) lead selenite honeycomb lattices hosting Cu(I)Cl2 groups
      obtained by chemical vapor transport reactions.
AB  - Chemical vapor transport (CVT) reactions were used to prepare three modular mixed
      valent Cu(I)-Cu(II) compounds, (Pb2Cu(2+)9O4)(SeO3)4(Cu(+)Cl(2))Cl5 (1),
      (PbCu(2+)5O2)(SeO3)2(Cu(+)Cl2)Cl3 (2), and (Pb(x)Cu(2+)(6
      x)O2)(SeO3)2(Cu(+)Cl2)K(1-x)Cl(4-x) (x = 0.20) (3). In their crystal structures
      chains of anion-centered (OCu(2+)4) and (OCu(2+)3Pb) tetrahedra form honeycomb
      like double layers with cavities occupied by linear [Cu(+)Cl2](-) groups.

PMID- 25971956
TI  - Bandgap Tuning of Silicon Quantum Dots by Surface Functionalization with
      Conjugated Organic Groups.
AB  - The quantum confinement and enhanced optical properties of silicon quantum dots
      (SiQDs) make them attractive as an inexpensive and nontoxic material for a
      variety of applications such as light emitting technologies (lighting, displays,
      sensors) and photovoltaics. However, experimental demonstration of these
      properties and practical application into optoelectronic devices have been
      limited as SiQDs are generally passivated with covalently bound insulating alkyl
      chains that limit charge transport. In this work, we show that strategically
      designed triphenylamine-based surface ligands covalently bonded to the SiQD
      surface using conjugated vinyl connectivity results in a 70 nm red-shifted
      photoluminescence relative to their decyl-capped control counterparts. This
      suggests that electron density from the SiQD is delocalized into the surface
      ligands to effectively create a larger hybrid QD with possible macroscopic charge
      transport properties. 

PMID- 25971955
TI  - Cross-sectional analysis of nutrition and serum uric acid in two Caucasian
      cohorts: the AusDiab Study and the Tromso study.
AB  - BACKGROUND: Hyperuricemia can lead to gout, and may be a risk factor for
      cardiovascular events, hypertension, diabetes and renal disease. There is well
      known link between gout and habitual intake of meat and seafood, however the
      association between hyperuricemia and micro-and macro-nutrient intake has not
      been established. METHODS: We studied associations between intakes of food
      categories, macro-and micronutrients and serum uric acid (SUA) levels in two
      cross-sectional surveys of Caucasian adults deriving from different food
      traditions: Australian Diabetes, Obesity and Lifestyle Study 1999/00 (n=9734, age
      25-91) and Tromso Study 4 1994/95 (n = 3031, age 25-69). Dietary intake was
      calculated from self-administered Food Frequency Questionnaires. In some analyses
      we stratified according to abdominal obesity status and gender. RESULTS: In both
      cohorts, lower levels of SUA were found in subjects with higher consumption of
      carbohydrates, calcium and vitamin B2, while higher fat intake was associated
      with higher SUA, after adjustment for age, body mass index, estimated glomerular
      filtration rate, physical activity, total energy intake, use of diuretics,
      presence of hypertension, diabetes and gout. Among individual food items, high
      consumption of dairy products, high-fibre bread, cereals and fruits were
      associated with lower SUA in most subject groups while consumption of meat, eggs,
      beer and spirits, but not wine, with elevated levels. CONCLUSIONS: Healthy food
      choices with high intake of carbohydrates, dairy products, fiber and
      micronutrient-rich foods, and limited intake of fat, beer and spirits, might be
      recommended to prevent high SUA. Dietary factors seem to have qualitatively
      similar impact on SUA in obese and non-obese men and women from Australia and
      Norway.

PMID- 25971957
TI  - Prophylactic administration of ondansetron in prevention of intrathecal morphine
      induced pruritus and post-operative nausea and vomiting in patients undergoing
      caesarean section.
AB  - BACKGROUND: Intrathecal morphine is commonly used for post caesarean analgesia.
      However, their use is frequently associated with the incidence of troublesome
      side effects such as nausea, vomiting and pruritus. Various mechanisms have been
      postulated for the opioid-induced pruritus, with a variety of medications with
      different mechanisms of actions formulated for the prevention and treatment. But,
      the results are inconsistent and hence the prevention and treatment of opioid
      induced pruritus still remains a challenge. Ondansetron which is antiemetic, non
      sedative and has no antianalgesic effect is an antagonist to 5-HT3 receptor, the
      receptor with which opioids interacts and imparts its effects. Ondansetron, thus,
      would be an attractive treatment strategy for both opioid-induced pruritus and
      post-operative nausea and vomiting. METHODS: After the approval from
      institutional review committee and written consent received from the patient, 50
      healthy parturients of ASA I and II physical status undergoing caesarean section
      under spinal anaesthesia were enrolled for the study. They were randomly
      categorized into placebo group (2 ml normal saline) and treatment group (2 ml of
      4 mg ondansetron), each group containing 25 patients. Pruritus and post-operative
      nausea and vomiting scores were recorded up to 24 hours after the administration
      of intrathecal morphine. Statistical analysis was performed using chi-square
      test. RESULTS: The incidence, severity and necessity of treatment for pruritus in
      the treatment group was significantly reduced compared to the placebo group (16%
      vs 88%). Similarly, the risk of post-operative nausea and vomiting in the
      treatment group was less compared to the placebo group (8% vs 56%). CONCLUSION:
      Prophylactic administration of ondansetron to parturients receiving intrathecal
      morphine for post-operative analgesia provides a significant reduction of
      intrathecal morphine-induced pruritus and nausea and vomiting. TRIAL
      REGISTRATION: CTRI/2015/01/005362 registered on 07/01/2015 in Clinical Trials
      Registry-India (ctri.nic.in).

PMID- 25971958
TI  - Perioperative Bundle Decreases Postoperative Hepatic Surgery Infections.
AB  - BACKGROUND: Postoperative infections are a costly and morbid complication. The
      introduction of perioperative infection prevention bundles have decreased
      surgical site infections (SSIs) in patients undergoing colorectal and pancreatic
      surgery. AIM: The purpose of this study was to determine if the implementation of
      a perioperative bundle would reduce postoperative infectious complications in
      patients undergoing hepatic surgery. METHODS: An evidence-based, low cost,
      perioperative infection bundle was created, and a retrospective review of a
      prospectively maintained database was performed on 163 consecutive patients
      undergoing hepatic surgery. Patient characteristics, operative details, outcomes,
      and complications were reviewed, and differences pre- and post-bundle were
      assessed with univariate and multivariate analyses. RESULTS: A total of 113
      patients received standard infection prophylaxis, while 50 received the
      perioperative bundle. Twenty-five patients had infections (16 deep abscesses, 3
      superficial SSIs, 4 urinary tract infections, 1 pneumonia, 1 bacteremia). The
      overall infection rate decreased from 20.4 % (23/133) pre-bundle to 4 % (2/50)
      post-bundle. The SSI rate also decreased from 15 % (17/113) to 4 % (2/50).
      Univariate analysis showed that institution of the bundle was associated with a
      lower overall infection rate (p = 0.008), lower SSI rate (p = 0.06), and lower
      overall complication rate (p = 0.04). Multivariate analysis confirmed that the
      use of the bundle was independently associated with a lower infection (p = 0.008)
      and SSI (p = 0.05) rate. The primary length of stay (LOS) and LOS for 60 days
      postoperatively both significantly decreased post-bundle (from median of 5-4
      days, p <= 0.001; 6-4 days, p <= 0.001). CONCLUSIONS: Implementation of a
      perioperative infection prevention bundle significantly decreased overall
      infections, SSIs, and postoperative LOS in patients undergoing hepatic surgery.

PMID- 25971959
TI  - Management and Prevention of Breast Cancer After Radiation to the Chest for
      Childhood, Adolescent, and Young Adulthood Malignancy.
AB  - BACKGROUND: Women treated with chest irradiation for childhood, adolescent, and
      young adulthood (CAYA) malignancies, in particular Hodgkin's lymphoma, have an
      increased risk of developing second cancers of the breast (SCB). However, there
      are few uniform guidelines regarding surveillance and prevention for this high
      risk group. METHODS: A systematic search using PUBMED and OVID MEDLINE was
      performed. Publications listed under the terms "breast neoplasm", "neoplasm,
      radiation-induced", "therapeutic radiation-induced breast cancer", "screening",
      "surveillance", "prevention", and "prophylaxis" between January 1992 and January
      2015 were assessed. RESULTS: A total of 138 publications were reviewed. Factors
      associated with increased SCB risk include young age at irradiation, prolong
      duration since irradiation (peak relative risk 13.87 at 15-19 years
      postradiation), and increased radiation dose and field. Early menopause reduces
      SCB risk. Annual screening mammography and breast MRI is recommended from age 25
      or 8 years posttreatment for women treated with >=20 Gy chest radiation before
      age 30 years. Compared with sporadic primary breast cancers (PBC), SCB more often
      are bilateral (6-34 %), managed with mastectomy (56-100 %), hormone receptor
      negative (27-49 %), and high-grade (35 %). Women with SCB have a similar breast
      cancer event-free survival and breast cancer-specific survival compared to women
      with PBC. However, their overall survival is worse due to comorbid conditions.
      There is paucity of information regarding secondary prevention of SCB.
      CONCLUSIONS: Survivors of CAYA malignancy are at risk of many late effects,
      including iatrogenic breast cancer from chest irradiation. They are best managed
      in a multidisciplinary late-effects setting where tailored risk management can be
      provided.

PMID- 25971961
TI  - Still defining optimal primaquine therapy against relapse after 63 years of
      continuous use.

PMID- 25971960
TI  - Receptor Tyrosine Kinase Expression Predicts Response to Sunitinib in Breast
      Cancer.
AB  - BACKGROUND: Preliminary data indicate that tyrosine kinase inhibitors (TKIs)
      function through rearranged during transfection (RET) in breast cancer. However,
      TKIs are not specific and can block several receptor tyrosine kinases (RTKs).
      This study used cell lines and primary breast cancer specimens to determine
      factors associated with TKI response. METHODS: Proliferation was assessed after
      short interfering RNA knockdown with or without sunitinib in breast cancer cell
      lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide).
      Breast cancer tissue and matched normal breast was obtained from 30 women with
      invasive breast carcinoma. Gene expression was assessed by reverse transcriptase
      polymerase chain reaction. Fresh tissue was treated in vitro with sunitinib or
      control media for 30 min, and response was assessed by phosphorylation-specific
      western blot. RESULTS: The RTKs including epidermal growth factor receptor
      (EGFR), vascular endothelial growth factor receptor (VEGFR1-3), platelet-derived
      growth factor receptor (PDGFRa/b), and Kit were overexpressed in triple-negative
      breast tumors relative to HER2- and estrogen receptor-alpha (ERalpha)-positive
      tumors and normal breast tissue. Knockdown of EGFR reduced in vitro proliferation
      in MCF-7 and MDA-MB-231 but not in SKBR-3 or ZR-75-1 breast cancer cells. With
      the exception of RET, response to sunitinib was independent of RTK expression in
      all four cell lines. Both ERalpha-positive and low-EGFR-expressing tumors had an
      increased in vitro sunitinib response, as determined by alteration of Erk
      activation. Expression of other RTKs and additional clinical factors were not
      associated with response. CONCLUSION: Triple-negative breast cancers overexpress
      RTKs but have decreased in vitro response to the TKI sunitinib. In addition to
      RET, TKIs that block EGFR may increase the therapeutic efficacy of TKIs in breast
      cancer.

PMID- 25971962
TI  - Structural Characterization of Phosducin and Its Complex with the 14-3-3 Protein.
AB  - Phosducin (Pdc), a highly conserved phosphoprotein involved in the regulation of
      retinal phototransduction cascade, transcriptional control, and modulation of
      blood pressure, is controlled in a phosphorylation-dependent manner, including
      the binding to the 14-3-3 protein. However, the molecular mechanism of this
      regulation is largely unknown. Here, the solution structure of Pdc and its
      interaction with the 14-3-3 protein were investigated using small angle x-ray
      scattering, time-resolved fluorescence spectroscopy, and hydrogen-deuterium
      exchange coupled to mass spectrometry. The 14-3-3 protein dimer interacts with
      Pdc using surfaces both inside and outside its central channel. The N-terminal
      domain of Pdc, where both phosphorylation sites and the 14-3-3-binding motifs are
      located, is an intrinsically disordered protein that reduces its flexibility in
      several regions without undergoing dramatic disorder-to-order transition upon
      binding to 14-3-3. Our data also indicate that the C-terminal domain of Pdc
      interacts with the outside surface of the 14-3-3 dimer through the region
      involved in Gtbetagamma binding. In conclusion, we show that the 14-3-3 protein
      interacts with and sterically occludes both the N- and C-terminal Gtbetagamma
      binding interfaces of phosphorylated Pdc, thus providing a mechanistic
      explanation for the 14-3-3-dependent inhibition of Pdc function. 

PMID- 25971963
TI  - The Melibiose Transporter of Escherichia coli: CRITICAL CONTRIBUTION OF LYS-377
      TO THE STRUCTURAL ORGANIZATION OF THE INTERACTING SUBSTRATE BINDING SITES.
AB  - We examine the role of Lys-377, the only charged residue in helix XI, on the
      functional mechanism of the Na(+)-sugar melibiose symporter from Escherichia
      coli. Intrinsic fluorescence, FRET, and Fourier transform infrared difference
      spectroscopy reveal that replacement of Lys-377 with either Cys, Val, Arg, or Asp
      disables both Na(+) and melibiose binding. On the other hand, molecular dynamics
      simulations extending up to 200-330 ns reveal that Lys-377 (helix XI) interacts
      with the anionic side chains of two of the three putative ligands for cation
      binding (Asp-55 and Asp-59 in helix II). When Asp-59 is protonated during the
      simulations, Lys-377 preferentially interacts with Asp-55. Interestingly, when a
      Na(+) ion is positioned in the Asp-55-Asp-59 environment, Asp-124 in helix IV (a
      residue essential for melibiose binding) reorients and approximates the Asp-55
      Asp-59 pair, and all three acidic side chains act as Na(+) ligands. Under these
      conditions, the side chain of Lys-377 interacts with the carboxylic moiety of
      these three Asp residues. These data highlight the crucial role of the Lys-377
      residue in the spatial organization of the Na(+) binding site. Finally, the
      analysis of the second-site revertants of K377C reveals that mutation of Ile-22
      (in helix I) preserves Na(+) binding, whereas that of melibiose is largely
      abolished according to spectroscopic measurements. This amino acid is located in
      the border of the sugar-binding site and might participate in sugar binding
      through apolar interactions. 

PMID- 25971964
TI  - Light-induced Changes in the Dimerization Interface of Bacteriophytochromes.
AB  - Phytochromes are dimeric photoreceptor proteins that sense red light levels in
      plants, fungi, and bacteria. The proteins are structurally divided into a light
      sensing photosensory module consisting of PAS, GAF, and PHY domains and a
      signaling output module, which in bacteriophytochromes typically is a histidine
      kinase (HK) domain. Existing structural data suggest that two dimerization
      interfaces exist between the GAF and HK domains, but their functional roles
      remain unclear. Using mutational, biochemical, and computational analyses of the
      Deinococcus radiodurans phytochrome, we demonstrate that two dimerization
      interfaces between sister GAF and HK domains stabilize the dimer with
      approximately equal contributions. The existence of both dimerization interfaces
      is critical for thermal reversion back to the resting state. We also find that a
      mutant in which the interactions between the GAF domains were removed monomerizes
      under red light. This implies that the interactions between the HK domains are
      significantly altered by photoconversion. The results suggest functional
      importance of the dimerization interfaces in bacteriophytochromes. 

PMID- 25971965
TI  - Computation and Functional Studies Provide a Model for the Structure of the Zinc
      Transporter hZIP4.
AB  - Members of the Zrt and Irt protein (ZIP) family are a central participant in
      transition metal homeostasis as they function to increase the cytosolic
      concentration of zinc and/or iron. However, the lack of a crystal structure
      hinders elucidation of the molecular mechanism of ZIP proteins. Here, we employed
      GREMLIN, a co-evolution-based contact prediction approach in conjunction with the
      Rosetta structure prediction program to construct a structural model of the human
      (h) ZIP4 transporter. The predicted contact data are best fit by modeling hZIP4
      as a dimer. Mutagenesis of residues that comprise a central putative hZIP4
      transmembrane transition metal coordination site in the structural model alter
      the kinetics and specificity of hZIP4. Comparison of the hZIP4 dimer model to all
      known membrane protein structures identifies the 12-transmembrane monomeric
      Piriformospora indica phosphate transporter (PiPT), a member of the major
      facilitator superfamily (MFS), as a likely structural homolog. 

PMID- 25971966
TI  - Interaction of alpha-Lipoic Acid with the Human Na+/Multivitamin Transporter
      (hSMVT).
AB  - The human Na(+)/multivitamin transporter (hSMVT) has been suggested to transport
      alpha-lipoic acid (LA), a potent antioxidant and anti-inflammatory agent used in
      therapeutic applications, e.g. in the treatment of diabetic neuropathy and
      Alzheimer disease. However, the molecular basis of the cellular delivery of LA
      and in particular the stereospecificity of the transport process are not well
      understood. Here, we expressed recombinant hSMVT in Pichia pastoris and used
      affinity chromatography to purify the detergent-solubilized protein followed by
      reconstitution of hSMVT in lipid bilayers. Using a combined approach encompassing
      radiolabeled LA transport and equilibrium binding studies in conjunction with the
      stabilized R-(+)- and S-(-)-enantiomers and the R,S-(+/-) racemic mixture of LA
      or lipoamide, we identified the biologically active form of LA, R-LA, to be the
      physiological substrate of hSMVT. Interaction of R-LA with hSMVT is strictly
      dependent on Na(+). Under equilibrium conditions, hSMVT can simultaneously bind
      ~2 molecules of R-LA in a biphasic binding isotherm with dissociation constants
      (Kd) of 0.9 and 7.4 MUm. Transport of R-LA in the oocyte and reconstituted system
      is exclusively dependent on Na(+) and exhibits an affinity of ~3 MUm. Measuring
      transport with known amounts of protein in proteoliposomes containing hSMVT in
      outside-out orientation yielded a catalytic turnover number (kcat) of about 1 s(
      1), a value that is well in agreement with other Na(+)-coupled transporters. Our
      data suggest that hSMVT-mediated transport is highly specific for R-LA at our
      tested concentration range, a finding with wide ramifications for the use of LA
      in therapeutic applications.

PMID- 25971967
TI  - Transient Receptor Potential Canonical 1 (TRPC1) Channels as Regulators of
      Sphingolipid and VEGF Receptor Expression: IMPLICATIONS FOR THYROID CANCER CELL
      MIGRATION AND PROLIFERATION.
AB  - The identity of calcium channels in the thyroid is unclear. In human follicular
      thyroid ML-1 cancer cells, sphingolipid sphingosine 1-phosphate (S1P), through
      S1P receptors 1 and 3 (S1P1/S1P3), and VEGF receptor 2 (VEGFR2) stimulates
      migration. We show that human thyroid cells express several forms of transient
      receptor potential canonical (TRPC) channels, including TRPC1. In TRPC1 knockdown
      (TRPC1-KD) ML-1 cells, the basal and S1P-evoked invasion and migration was
      attenuated. Furthermore, the expression of S1P3 and VEGFR2 was significantly down
      regulated. Transfecting wild-type ML-1 cells with a nonconducting TRPC1 mutant
      decreased S1P3 and VEGFR2 expression. In TRPC1-KD cells, receptor-operated
      calcium entry was decreased. To investigate whether the decreased receptor
      expression was due to attenuated calcium entry, cells were incubated with the
      calcium chelator BAPTA-AM (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid). In these cells, and in cells where calmodulin and calmodulin-dependent
      kinase were blocked pharmacologically, S1P3 and VEGFR2 expression was decreased.
      In TRPC1-KD cells, both hypoxia-inducible factor 1alpha expression and the
      secretion and activity of MMP2 and MMP9 were attenuated, and proliferation was
      decreased in TRPC1-KD cells. This was due to a prolonged G1 phase of the cell
      cycle, a significant increase in the expression of the cyclin-dependent kinase
      inhibitors p21 and p27, and a decrease in the expression of cyclin D2, cyclin D3,
      and CDK6. Transfecting TRPC1 to TRPC1-KD cells rescued receptor expression,
      migration, and proliferation. Thus, the expression of S1P3 and VEGFR2 is mediated
      by a calcium-dependent mechanism. TRPC1 has a crucial role in this process. This
      regulation is important for the invasion, migration, and proliferation of thyroid
      cancer cells. 

PMID- 25971968
TI  - Specific Activation of the Plant P-type Plasma Membrane H+-ATPase by
      Lysophospholipids Depends on the Autoinhibitory N- and C-terminal Domains.
AB  - Eukaryotic P-type plasma membrane H(+)-ATPases are primary active transport
      systems that are regulated at the post-translation level by cis-acting
      autoinhibitory domains, which can be relieved by protein kinase-mediated
      phosphorylation or binding of specific lipid species. Here we show that
      lysophospholipids specifically activate a plant plasma membrane H(+)-ATPase
      (Arabidopsis thaliana AHA2) by a mechanism that involves both cytoplasmic
      terminal domains of AHA2, whereas they have no effect on the fungal counterpart
      (Saccharomyces cerevisiae Pma1p). The activation was dependent on the glycerol
      backbone of the lysophospholipid and increased with acyl chain length, whereas
      the headgroup had little effect on activation. Activation of the plant pump by
      lysophospholipids did not involve the penultimate residue, Thr-947, which is
      known to be phosphorylated as part of a binding site for activating 14-3-3
      protein, but was critically dependent on a single autoinhibitory residue (Leu
      919) upstream of the C-terminal cytoplasmic domain in AHA2. A corresponding
      residue is absent in the fungal counterpart. These data indicate that plant
      plasma membrane H(+)-ATPases evolved as specific receptors for lysophospholipids
      and support the hypothesis that lysophospholipids are important plant signaling
      molecules. 

PMID- 25971969
TI  - Functional Genomic Screen Identifies Klebsiella pneumoniae Factors Implicated in
      Blocking Nuclear Factor kappaB (NF-kappaB) Signaling.
AB  - Klebsiella pneumoniae is an etiologic agent of community-acquired and nosocomial
      pneumonia. It has been shown that K. pneumoniae infections are characterized by
      reduced early inflammatory response. Recently our group has shown that K.
      pneumoniae dampens the activation of inflammatory responses by antagonizing the
      activation of the NF-kappaB canonical pathway. Our results revealed that K.
      pneumoniae capsule polysaccharide (CPS) was necessary but not sufficient to
      attenuate inflammation. To identify additional Klebsiella factors required to
      dampen inflammation, we standardized and applied a high-throughput gain-of
      function screen to examine a Klebsiella transposon mutant library. We identified
      114 mutants that triggered the activation of NF-kappaB. Two gene ontology
      categories accounted for half of the loci identified in the screening: metabolism
      and transport genes (32% of the mutants) and envelope-related genes (17%).
      Characterization of the mutants revealed that the lack of the enterobactin
      siderophore was linked to a reduced CPS expression, which in turn underlined the
      NF-kappaB activation induced by the mutant. The lipopolysaccharide (LPS) O
      polysaccharide and the pullulanase (PulA) type 2 secretion system (T2SS) are
      required for full effectiveness of the immune evasion. Importantly, these factors
      do not play a redundant role. The fact that LPS O-polysaccharide and T2SS mutant
      induced responses were dependent on TLR2-TLR4-MyD88 activation suggested that LPS
      O-polysaccharide and PulA perturbed Toll-like receptor (TLR)-dependent
      recognition of K. pneumoniae. Finally, we demonstrate that LPS O-polysaccharide
      and pulA mutants are attenuated in the pneumonia mouse model. We propose that LPS
      O-polysaccharide and PulA T2SS could be new targets for the design of new
      antimicrobials. Increasing TLR-governed defense responses might provide also
      selective alternatives for the management of K. pneumoniae pneumonia. 

PMID- 25971970
TI  - Snail Is a Direct Target of Hypoxia-inducible Factor 1alpha (HIF1alpha) in
      Hypoxia-induced Endothelial to Mesenchymal Transition of Human Coronary
      Endothelial Cells.
AB  - Endothelial to mesenchymal transition (EndMT) was originally described in heart
      development where the endocardial endothelial cells that line the
      atrioventricular canal undergo an EndMT to form the endocardial mesenchymal
      cushion that later gives rise to the septum and mitral and tricuspid valves. In
      the postnatal heart specifically, endothelial cells that originate from the
      endocardium maintain increased susceptibility to undergo EndMT as remnants from
      their embryonic origin. Such EndMT involving adult coronary endothelial cells
      contributes to microvascular rarefaction and subsequent chronification of hypoxia
      in the injured heart, ultimately leading to cardiac fibrosis. Although in most
      endothelial beds hypoxia induces tip cell formation and sprouting angiogenesis,
      here we demonstrate that hypoxia is a stimulus for human coronary endothelial
      cells to undergo phenotypic changes reminiscent of EndMT via a mechanism
      involving hypoxia-inducible factor 1alpha-induced activation of the EndMT master
      regulatory transcription factor SNAIL. Our study adds further evidence for the
      unique susceptibility of endocardium-derived endothelial cells to undergo EndMT
      and provides novel insights into how hypoxia contributes to progression of
      cardiac fibrosis. Additional studies may be required to discriminate between
      distinct sprouting angiogenesis and EndMT responses of different endothelial
      cells populations. 

PMID- 25971972
TI  - Platymonas subcordiformis Channelrhodopsin-2 Function: I. THE PHOTOCHEMICAL
      REACTION CYCLE.
AB  - The photocycle kinetics of Platymonas subcordiformis channelrhodopsin-2 (PsChR2),
      among the most highly efficient light-gated cation channels and the most blue
      shifted channelrhodopsin, was studied by time-resolved absorption spectroscopy in
      the 340-650-nm range and in the 100-ns to 3-s time window. Global exponential
      fitting of the time dependence of spectral changes revealed six lifetimes: 0.60
      MUs, 5.3 MUs, 170 MUs, 1.4 ms, 6.7 ms, and 1.4 s. The sequential intermediates
      derived for a single unidirectional cycle scheme based on these lifetimes were
      found to contain mixtures of K, L, M, O, and P molecular states, named in analogy
      to photointermediates in the bacteriorhodopsin photocycle. The photochemistry is
      described by the superposition of two independent parallel photocycles. The
      analysis revealed that 30% of the photoexcited receptor molecules followed Cycle
      1 through the K, M, O, and P states, whereas 70% followed Cycle 2 through the K,
      L, M, and O states. The recovered state, R, is spectrally close, but not
      identical, to the dark state on the seconds time scale. The two-cycle model of
      this high efficiency channelrhodopsin-2 (ChR) opens new perspectives in
      understanding the mechanism of channelrhodopsin function. 

PMID- 25971971
TI  - Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain.
AB  - Metabotropic (slow) and ionotropic (fast) neurotransmission are integrated by
      intracellular signal transduction mechanisms involving protein
      phosphorylation/dephosphorylation to achieve experience-dependent alterations in
      brain circuitry. ERK is an important effector of both slow and fast forms of
      neurotransmission and has been implicated in normal brain function and CNS
      diseases. Here we characterize phosphorylation of the ERK-activating protein
      kinase MEK1 by Cdk5, ERK, and Cdk1 in vitro in intact mouse brain tissue and in
      the context of an animal behavioral paradigm of stress. Cdk5 only phosphorylates
      Thr-292, whereas ERK and Cdk1 phosphorylate both Thr-292 and Thr-286 MEK1. These
      sites interact in a kinase-specific manner and inhibit the ability of MEK1 to
      activate ERK. Thr-292 and Thr-286 MEK1 are phosphorylated in most mouse brain
      regions to stoichiometries of ~5% or less. Phosphorylation of Thr-292 MEK1 is
      regulated by cAMP-dependent signaling in mouse striatum in a manner consistent
      with negative feedback inhibition in response to ERK activation. Protein
      phosphatase 1 and 2A contribute to the maintenance of the basal phosphorylation
      state of both Thr-292 and Thr-286 MEK1 and that of ERK. Activation of the NMDA
      class of ionotropic glutamate receptors reduces inhibitory MEK1 phosphorylation,
      whereas forced swim, a paradigm of acute stress, attenuates Thr-292 MEK1
      phosphorylation. Together, the data indicate that these inhibitory MEK1 sites
      phosphorylated by Cdk5 and ERK1 serve as mechanistic points of convergence for
      the regulation of ERK signaling by both slow and fast neurotransmission.

PMID- 25971973
TI  - Ubiquitous Autofragmentation of Fluorescent Proteins Creates Abundant Defective
      Ribosomal Products (DRiPs) for Immunosurveillance.
AB  - Green fluorescent protein (GFP) and other fluorescent proteins are essential
      tools for biological research. When fused to peptides or proteins as a reporter,
      GFP enables localization and quantitation of gene products in otherwise
      unmanipulated live cells or organisms. We previously reported that a sizable
      fraction of nascent GFP is post-translationally converted into a 20-kDa Triton X
      100-insoluble proteasome substrate (Qian, S. B., Princiotta, M. F., Bennink, J.
      R., and Yewdell, J. W. (2006) J. Biol. Chem. 281, 392-400; Dolan, B. P., Li, L.,
      Veltri, C. A., Ireland, C. M., Bennink, J. R., and Yewdell, J. W. (2011) J.
      Immunol. 186, 2065-2072). Here, we show that a similarly sized fragment is
      generated by all GFP and red fluorescent protein family members we examined. We
      demonstrate that fragmentation is a by-product of GFP chromophore rearrangement.
      A non-rearranging GFP mutant fails to fragment and generates diminished levels of
      K(b)-SIINFEKL complexes when SIINFEKL is genetically fused to either the C- or N
      terminal domains of GFP fusion proteins. Instructively, another fragmenting GFP
      mutant that cannot create the functional chromophore but still generates
      fragments also demonstrates diminished K(b)-SIINFEKL generation. However, the
      mutant and wild-type fragments differ fundamentally in that wild-type fragments
      are rapidly liberated from the intact molecule and degraded quickly, accounting
      for increased K(b)-SIINFEKL generation. In the fragmenting mutant, the fragments
      are generated slowly and remain associated, likely in a native conformation based
      on their original structural description (Barondeau, D. P., Kassmann, C. J.,
      Tainer, J. A., and Getzoff, E. D. (2006) J. Am. Chem. Soc. 128, 4685-4693). The
      wild-type GFP fragments represent the first biochemically defined natural
      defective ribosomal products to contribute peptides for immunosurveillance,
      enabling quantitation of peptide generation efficiency from this source of
      defective ribosomal products. More broadly, given the wide use of fluorescent
      proteins, their ubiquitous and abundant fragmentation must be considered when
      interpreting experiments using these extremely useful probes. 

PMID- 25971974
TI  - The tRNA Splicing Endonuclease Complex Cleaves the Mitochondria-localized CBP1
      mRNA.
AB  - The tRNA splicing endonuclease (Sen) complex is located on the mitochondrial
      outer membrane and splices precursor tRNAs in Saccharomyces cerevisiae. Here, we
      demonstrate that the Sen complex cleaves the mitochondria-localized mRNA encoding
      Cbp1 (cytochrome b mRNA processing 1). Endonucleolytic cleavage of this mRNA
      required two cis-elements: the mitochondrial targeting signal and the stem-loop
      652-726-nt region. Mitochondrial localization of the Sen complex was required for
      cleavage of the CBP1 mRNA, and the Sen complex cleaved this mRNA directly in
      vitro. We propose that the Sen complex cleaves the CBP1 mRNA, which is co
      translationally localized to mitochondria via its mitochondrial targeting signal.

PMID- 25971975
TI  - Diversity in Overall Activity Regulation of Ribonucleotide Reductase.
AB  - Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the
      corresponding deoxyribonucleotides, which are used as building blocks for DNA
      replication and repair. This process is tightly regulated via two allosteric
      sites, the specificity site (s-site) and the overall activity site (a-site). The
      a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and
      functions as an on/off switch, whereas the composite s-site binds ATP, dATP,
      dTTP, or dGTP and determines which substrate to reduce. There are three classes
      of RNRs, and class I RNRs consist of different combinations of alpha and beta
      subunits. In eukaryotic and Escherichia coli class I RNRs, dATP inhibits enzyme
      activity through the formation of inactive alpha6 and alpha4beta4 complexes,
      respectively. Here we show that the Pseudomonas aeruginosa class I RNR has a
      duplicated ATP cone domain and represents a third mechanism of overall activity
      regulation. Each alpha polypeptide binds three dATP molecules, and the N-terminal
      ATP cone is critical for binding two of the dATPs because a truncated protein
      lacking this cone could only bind dATP to its s-site. ATP activates the enzyme
      solely by preventing dATP from binding. The dATP-induced inactive form is an
      alpha4 complex, which can interact with beta2 to form a non-productive
      alpha4beta2 complex. Other allosteric effectors induce a mixture of alpha2 and
      alpha4 forms, with the former being able to interact with beta2 to form active
      alpha2beta2 complexes. The unique features of the P. aeruginosa RNR are
      interesting both from evolutionary and drug discovery perspectives. 

PMID- 25971977
TI  - Three Pseudomonas putida FNR Family Proteins with Different Sensitivities to O2.
AB  - The Escherichia coli fumarate-nitrate reduction regulator (FNR) protein is the
      paradigm for bacterial O2-sensing transcription factors. However, unlike E. coli,
      some bacterial species possess multiple FNR proteins that presumably have evolved
      to fulfill distinct roles. Here, three FNR proteins (ANR, PP_3233, and PP_3287)
      from a single bacterial species, Pseudomonas putida KT2440, have been analyzed.
      Under anaerobic conditions, all three proteins had spectral properties resembling
      those of [4Fe-4S] proteins. The reactivity of the ANR [4Fe-4S] cluster with O2
      was similar to that of E. coli FNR, and during conversion to the apo-protein, via
      a [2Fe-2S] intermediate, cluster sulfur was retained. Like ANR, reconstituted
      PP_3233 and PP_3287 were converted to [2Fe-2S] forms when exposed to O2, but
      their [4Fe-4S] clusters reacted more slowly. Transcription from an FNR-dependent
      promoter with a consensus FNR-binding site in P. putida and E. coli strains
      expressing only one FNR protein was consistent with the in vitro responses to O2.
      Taken together, the experimental results suggest that the local environments of
      the iron-sulfur clusters in the different P. putida FNR proteins influence their
      reactivity with O2, such that ANR resembles E. coli FNR and is highly responsive
      to low concentrations of O2, whereas PP_3233 and PP_3287 have evolved to be less
      sensitive to O2. 

PMID- 25971978
TI  - Platymonas subcordiformis Channelrhodopsin-2 (PsChR2) Function: II. RELATIONSHIP
      OF THE PHOTOCHEMICAL REACTION CYCLE TO CHANNEL CURRENTS.
AB  - Channelrhodopsins, such as the algal phototaxis receptor Platymonas
      subcordiformis channelrhodopsin-2 (PsChR2), are light-gated cation channels used
      as optogenetic tools for photocontrol of membrane potential in living cells.
      Channelrhodopsin (ChR)-mediated photocurrent responses are complex and poorly
      understood, exhibiting alterations in peak current amplitude, extents and
      kinetics of inactivation, and kinetics of the recovery of the prestimulus dark
      current that are sensitive to duration and frequency of photostimuli. From the
      analysis of time-resolved optical absorption data, presented in the accompanying
      article, we derived a two-cycle model that describes the photocycles of PsChR2.
      Here, we applied the model to evaluate the transient currents produced by PsChR2
      expressed in HEK293 cells under both fast laser excitation and step-like
      continuous illumination. Interpretation of the photocurrents in terms of the
      photocycle kinetics indicates that the O states in both cycles are responsible
      for the channel current and fit the current transients under the different
      illumination regimes. The peak and plateau currents in response to a single light
      step, a train of light pulses, and a light step superimposed on a continuous
      light background observed for ChR2 proteins are explained in terms of
      contributions from the two parallel photocycles. The analysis shows that the peak
      current desensitization and recovery phenomena are inherent properties of the
      photocycles. The light dependence of desensitization is reproduced and explained
      by the time evolution of the concentration transients in response to step-like
      illumination. Our data show that photocycle kinetic parameters are sufficient to
      explain the complex dependence of photocurrent responses to photostimuli. 

PMID- 25971976
TI  - Insulin-like Growth Factor 2 Overexpression Induces beta-Cell Dysfunction and
      Increases Beta-cell Susceptibility to Damage.
AB  - The human insulin-like growth factor 2 (IGF2) and insulin genes are located
      within the same genomic region. Although human genomic studies have demonstrated
      associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding
      protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully
      understood. We previously described that transgenic mice overexpressing IGF2
      specifically in beta-cells (Tg-IGF2) develop a pre-diabetic state. Here, we
      characterized the effects of IGF2 on beta-cell functionality. Overexpression of
      IGF2 led to beta-cell dedifferentiation and endoplasmic reticulum stress causing
      islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and
      treatment of adult wild-type islets with recombinant IGF2 in vitro further
      confirmed the direct implication of IGF2 on beta-cell dysfunction. Treatment of
      Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice
      with a transgenic model of islet lymphocytic infiltration promoted the
      development of overt diabetes, suggesting that IGF2 makes islets more susceptible
      to beta-cell damage and immune attack. These results indicate that increased
      local levels of IGF2 in pancreatic islets may predispose to the onset of
      diabetes. This study unravels an unprecedented role of IGF2 on beta-cells
      function. 

PMID- 25971979
TI  - The Effect of Isthmus on Vertical Root Fracture in Endodontically Treated Teeth.
AB  - INTRODUCTION: Vertical root fracture (VRF) from apical condensation of gutta
      percha is a common failure mode in endodontically treated teeth. Virtually all
      previous studies of VRF are limited to 1-canal roots. In this study, we consider
      experimentally and analytically VRF in roots with 2 canals. METHODS: The interior
      root morphology in mandibular molar teeth extracted from patients due to VRF or
      other reason was examined from a series of polished horizontal cross sections. A
      2-dimensional fracture mechanics analysis was used to determine crack growth from
      the canal surface to the outer root surface and evaluate the apical load needed
      to cause VRF, Fmax. RESULTS: From a mechanistic viewpoint, the isthmus connecting
      root canals can be regarded as a natural weak plane or crack. The results expose
      the prime role of isthmus in reducing Fmax, from ~ 50 N with no isthmus present
      to ~ 10 N. CONCLUSIONS: Two-canal mesial roots are much more prone to VRF than 1
      canal distal roots. We suggest that VRF may occur during clinical condensation of
      gutta-percha in mesial roots of mandibular molars as well as other roots with
      canals connected by isthmus.

PMID- 25971980
TI  - Oral contraceptives and antibiotics. A cross-sectional study about patients'
      knowledge in general practice.
AB  - BACKGROUND: The evidence regarding oral contraceptives and its effectiveness with
      concomitant ingestion of antibiotics is conflicting. Until evidence becomes
      clearer, patients should be aware of this possible interaction. The aim of this
      study was to assess the knowledge and the source of information about this
      interaction in GP patients in Austria. METHODS: Within the framework of the APRES
      study, 20 Austrian GPs were purposefully selected from among a GP research
      network and were asked to recruit 200 patients each. The patient cohort was asked
      to complete a questionnaire. Subsequent analysis included descriptive statistics,
      statistical tests and logistic regression models. FINDINGS: Overall, 3280
      questionnaires could be used for analysis. Of these, 29.7 % (n = 974) of patients
      acknowledged an awareness of the interaction of antibiotics with OCPs. Women
      under the age of 46 years acknowledged this interaction in 52.3 % of cases.
      Positive associations for the belief in an existing interaction in women were
      identified with age (OR 2.2) and having read the package inserts (OR 1.6).
      Further, belief was recognized in males based on age (OR 2.5) and tertiary
      education (OR 2.0). The main source of information regarding antibiotics was the
      GP (55.9 %). CONCLUSIONS: Less than one-third of all participants and half of the
      women in the reproductive age acknowledged an interaction between antibiotics and
      OCPs. Since the GP is the main source of information, this finding depicts a
      large potential for knowledge transfer within the primary health care setting. A
      multifaceted strategy is needed at both the population and the GP level to
      improve awareness and to address these educational gaps.

PMID- 25971981
TI  - Prevalence of pemphigus and pemphigoid autoantibodies in the general population.
AB  - BACKGROUND: Mucocutaneous blistering is characteristic of autoimmune bullous
      dermatoses (AIBD). Blisters are caused by autoantibodies directed against
      structural components of the skin. Hence, detection of specific autoantibodies
      has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD
      autoantibodies in healthy individuals yielded contradictory results. METHODS: To
      clarify this, samples from 7063 blood donors were tested for presence of anti
      BP180-NC16A, anti-BP230 and anti-Dsg1/3 IgG by indirect immunofluorescence (IF)
      microscopy using a biochip. RESULTS: Cumulative prevalence of these
      autoantibodies was 0.9 % (CI: 0.7-1.1 %), with anti-BP180-NC16A IgG being most
      prevalent. Validation of IF findings using ELISA confirmed presence of
      autoantibodies in 7/15 (anti-Dsg1), 6/7 (anti-Dsg3), 35/37 (anti-BP180-NC16A) and
      2/3 (anti-BP230) cases. Moreover, in 16 samples, anti-BP180-NC16A autoantibody
      concentrations exceeded the cut-off for the diagnosis of bullous pemphigoid.
      Interestingly, these anti-BP180-NC16A autoantibodies from healthy individuals
      formed immune complexes with recombinant antigen and dose-dependently activated
      neutrophils in vitro. However, fine-epitope mapping within NC16A showed a
      different binding pattern of anti-BP180-NC16A autoantibodies from healthy
      individuals compared to bullous pemphigoid patients, while IgG subclasses were
      identical. CONCLUSIONS: Collectively, we here report a low prevalence of AIBD
      autoantibodies in a large cohort of healthy individuals. Furthermore, functional
      analysis shows differences between autoantibodies from healthy donors and AIBD
      patients.

PMID- 25971982
TI  - X-shaped DNA potentiates therapeutic efficacy in colitis-associated colon cancer
      through dual activation of TLR9 and inflammasomes.
AB  - BACKGROUND: Immunotherapy has been extensively pursed as a promising strategy for
      the treatment of cancer. Pattern-recognition receptors (PRRs) play important
      roles in triggering activation of innate and adaptive immunity. Therefore, agents
      that stimulate PRRs could be useful for cancer immunotherapy. We developed two
      kinds of X-shaped double-stranded oligodeoxynucleotides (X-DNA), a single unit of
      X-DNA (XS-DNA) composed of four strands of DNA and a ligated X-DNA complex (XL
      DNA) formed by crosslinking each XS-DNA to the other, and investigated if they
      had immunostimulatory activity and could be applied to anti-cancer immunotherapy.
      METHODS: Activation of MAPKs and NF-kappaB was determined by immunoblotting in
      bone marrow-derived primary dendritic cells (BMDCs). Immune cytokines and co
      stimulatory molecules were measured by ELISA and flow cytometry analysis. Anti
      cancer efficacy was examined in an azoxymethane/dextran sulfate sodium-induced
      colitis-associated colon cancer mouse model. Association of X-DNA and TLR9 was
      determined by co-immunoprecipitation followed by immunoblotting. The involvement
      of TLR9 and inflammasomes was determined using TLR9- or caspase-1-deficient
      BMDCs. Inflammasome activation was examined by degradation of pro-caspase-1 to
      caspase-1 and cleavage of pro-IL-1beta to IL-1beta in BMDCs. RESULTS: XL-DNA and
      XS-DNA induced activation of MAPKs and NF-kappaB and production of immune
      cytokines and co-stimulatory molecules in BMDCs. BMDCs stimulated by XL-DNA
      induced differentiation of naive CD4(+) T cells to TH1 cells. Intravenous
      injection of XL-DNA into mice resulted in increased serum IFN-gamma and IL-12
      levels, showing in vivo efficacy of XL-DNA to activate TH1 cells and dendritic
      cells. XL-DNA greatly enhanced the therapeutic efficacy of doxorubicin, an anti
      cancer drug, in colitis-associated colon cancer. XL-DNA directly associated with
      TLR9. In addition, immunostimulatory activities of X-DNA were abolished in TLR9
      deficient dendritic cells. Furthermore, X-DNA induced caspase-1 degradation and
      IL-1beta secretion in BMDCs, which were abolished in caspase-1-deficient cells.
      CONCLUSIONS: X-DNA induced the activation of dendritic cells as shown by the
      expression of immune-cytokines and co-stimulatory molecules, resulting in the
      differentiation of TH1 cells, mediated through dual activation of TLR9 and
      inflammasomes. X-DNA represents a promising immune adjuvant that can enhance the
      therapeutic efficacy of anti-cancer drugs by activating PRRs.

PMID- 25971984
TI  - Fibromuscular dysplasia of the coronary arteries: a rare cause of death in
      infants and young children.
AB  - Fibromuscular dysplasia is a common vascular disease, which mainly affects the
      renal arteries. In this study, we report the case of a 1-day-old infant who
      presented with severe left ventricular dysfunction immediately after birth, and
      subsequently died 3 days postnatally. At autopsy, an extensive myocardial
      infarction of the left ventricle and the septum was found, caused by an isolated
      fibromuscular dysplasia of left coronary artery. 

PMID- 25971983
TI  - Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by
      Diabetes Mellitus.
AB  - Chronic inflammation appears to play a critical role in sickness behavior caused
      by diabetes mellitus. Astaxanthin has been used in treating diabetes mellitus and
      diabetic complications because of its neuroprotective and anti-inflammatory
      actions. However, whether astaxanthin can improve sickness behavior induced by
      diabetes and its potential mechanisms are still unknown. The aim of this study
      was to investigate the effects of astaxanthin on diabetes-elicited abnormal
      behavior in mice and its corresponding mechanisms. An experimental diabetic model
      was induced by streptozotocin (150 mg/kg) and astaxanthin (25 mg/kg/day) was
      provided orally for 10 weeks. Body weight and water consumption were measured,
      and the sickness behavior was evaluated by the open field test (OFT) and closed
      field test (CFT). The expression of glial fibrillary acidic protein (GFAP) was
      measured, and the frontal cortical cleaved caspase-3 positive cells, interleukin
      6 (IL-6), and interleukin-1beta (IL-1beta) expression levels were also
      investigated. Furthermore, cystathionine beta-synthase (CBS) in the frontal
      cortex was detected to determine whether the protective effect of astaxanthin on
      sickness behavior in diabetic mice is closely related to CBS. As expected, we
      observed that astaxanthin improved general symptoms and significantly increase
      horizontal distance and the number of crossings in the OFT and CFT. Furthermore,
      data showed that astaxanthin could decrease GFAP-positive cells in the brain and
      down-regulate the cleaved caspase-3, IL-6, and IL-1beta, and up-regulate CBS in
      the frontal cortex. These results suggest that astaxanthin provides
      neuroprotection against diabetes-induced sickness behavior through inhibiting
      inflammation, and the protective effects may involve CBS expression in the brain.

PMID- 25971985
TI  - Exploring the quantum critical behaviour in a driven Tavis-Cummings circuit.
AB  - Quantum phase transitions play an important role in many-body systems and have
      been a research focus in conventional condensed-matter physics over the past few
      decades. Artificial atoms, such as superconducting qubits that can be
      individually manipulated, provide a new paradigm of realising and exploring
      quantum phase transitions by engineering an on-chip quantum simulator. Here we
      demonstrate experimentally the quantum critical behaviour in a highly
      controllable superconducting circuit, consisting of four qubits coupled to a
      common resonator mode. By off-resonantly driving the system to renormalize the
      critical spin-field coupling strength, we have observed a four-qubit
      nonequilibrium quantum phase transition in a dynamical manner; that is, we sweep
      the critical coupling strength over time and monitor the four-qubit scaled
      moments for a signature of a structural change of the system's eigenstates. Our
      observation of the nonequilibrium quantum phase transition, which is in good
      agreement with the driven Tavis-Cummings theory under decoherence, offers new
      experimental approaches towards exploring quantum phase transition-related
      science, such as scaling behaviours, parity breaking and long-range quantum
      correlations. 

PMID- 25971986
TI  - Effect of an educational program on attitudes towards deceased organ donation.
AB  - BACKGROUND: Organ shortage for transplantation remains a serious global issue. We
      assessed the effects of an educational program on changing attitudes of medical
      students towards deceased organ donation. MATERIAL AND METHODS: We conducted a
      non-randomized trial involving medical students who had not previously signed a
      donor card. Third-year medical students (n=86, program group) received an
      information pamphlet followed by a 60-min classroom lecture by a transplant
      physician who was himself a kidney transplant recipient and finally another
      information pamphlet containing a donor card. First-year students (n=87, control
      group) received the same two pamphlets only. The primary outcome was signing a
      donor card. The secondary outcomes included willingness to sign a donor card,
      willingness to donate organs, family discussion about deceased organ donation,
      and knowledge. Outcomes were measured by questionnaires before and after the
      intervention. RESULTS: A higher proportion of students of the program group
      signed a donor card than the pamphlet group (8.1% vs. 0%, respectively). After
      propensity score adjustment, the program was associated with higher proportion of
      willingness to sign a donor card (91.9% vs. 73.6%; adjusted proportion ratio 1.28
      [95% CI 1.11-1.48]), family discussion (18.6% vs. 6.9%; 2.85 [1.15-7.03]), and
      increased knowledge. There were no significant differences between the two groups
      in willingness to donate organs after brain death (64.0% vs. 60.9%; 1.12 [0.90
      1.40]) and cardiac death (77.9% vs. 71.3%; 1.11 [0.93-1.33]). CONCLUSIONS: The
      educational program delivered by a transplant physician and a recipient may alter
      the attitudes of medical students towards deceased organ donation.

PMID- 25971988
TI  - Thyroid blockade in 123I-mIBG cardiac imaging: A common sense approach.

PMID- 25971987
TI  - Predictors of high-risk coronary artery disease in subjects with normal SPECT
      myocardial perfusion imaging.
AB  - BACKGROUND: While uncommon, normal stress SPECT myocardial perfusion imaging
      (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by
      invasive coronary angiography (ICA).The predictors of high-risk CAD in patients
      with normal SPECT-MPI have not been described. METHODS: We studied 580 patients
      (age 64 +/- 12 years, 49% men) without known CAD who underwent stress-gated SPECT
      MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed
      stress score (SSS) <4. High-risk CAD was defined as 3 vessels with >=70%
      stenosis, 2 vessels with >=70% stenosis including proximal left anterior
      descending, or left main with >=50% stenosis. Obstructive non-high-risk CAD was
      defined by the presence of a >=70% stenosis but without having other high-risk
      criteria. Tenfold cross-validated receiver operating characteristic (ROC)
      estimates were obtained to assess the predictors of high-risk CAD. RESULTS: Forty
      two subjects (7.2%) had high-risk CAD and 168 (29.0%) had obstructive non-high
      risk CAD. Variables associated with high-risk CAD were pretest probability of CAD
      >=66% (Odds ratio [OR] 3.63, 95% CI 1.6-8.3, P = .002), SSS > 0 (OR 7.46, 95% CI
      2.6-21.1, P < 0.001), and abnormal TID (OR 2.16, 95% CI 1.0-4.5, P = 0.044). When
      substituted for TID, EF change was also predictive of high-risk CAD (OR 0.93, 95%
      CI 0.9-1.0, P = 0.023). The prevalence of high-risk CAD increased as the number
      of these predictors increased. In a sub-analysis of patients in whom quantitative
      total perfusion deficit (TPD) was available, TPD > 0 was also a predictor of high
      risk CAD (OR 6.01, 95% CI 1.5-22.2, P = 0.011). CONCLUSION: Several clinical,
      stress, and SPECT-MPI findings are associated high-risk CAD among patients with
      normal SPECT-MPI. Consideration of these factors may improve the overall
      assessment of the likelihood of high-risk CAD in patients undergoing stress SPECT
      MPI.

PMID- 25971989
TI  - Nuclear cardiology as it should look in the twenty-first century.

PMID- 25971990
TI  - Immortality time and serial myocardial perfusion imaging: Only those who do not
      die may repeat the exam.

PMID- 25971991
TI  - GENLIB: an R package for the analysis of genealogical data.
AB  - BACKGROUND: Founder populations have an important role in the study of genetic
      diseases. Access to detailed genealogical records is often one of their
      advantages. These genealogical data provide unique information for researchers in
      evolutionary and population genetics, demography and genetic epidemiology.
      However, analyzing large genealogical datasets requires specialized methods and
      software. The GENLIB software was developed to study the large genealogies of the
      French Canadian population of Quebec, Canada. These genealogies are accessible
      through the BALSAC database, which contains over 3 million records covering the
      whole province of Quebec over four centuries. Using this resource, extended
      pedigrees of up to 17 generations can be constructed from a sample of present-day
      individuals. RESULTS: We have extended and implemented GENLIB as a package in the
      R environment for statistical computing and graphics, thus allowing optimal
      flexibility for users. The GENLIB package includes basic functions to manage
      genealogical data allowing, for example, extraction of a part of a genealogy or
      selection of specific individuals. There are also many functions providing
      information to describe the size and complexity of genealogies as well as
      functions to compute standard measures such as kinship, inbreeding and genetic
      contribution. GENLIB also includes functions for gene-dropping simulations. The
      goal of this paper is to present the full functionalities of GENLIB. We used a
      sample of 140 individuals from the province of Quebec (Canada) to demonstrate
      GENLIB's functions. Ascending genealogies for these individuals were
      reconstructed using BALSAC, yielding a large pedigree of 41,523 individuals.
      Using GENLIB's functions, we provide a detailed description of these genealogical
      data in terms of completeness, genetic contribution of founders, relatedness,
      inbreeding and the overall complexity of the genealogical tree. We also present
      gene-dropping simulations based on the whole genealogy to investigate identical
      by-descent sharing of alleles and chromosomal segments of different lengths and
      estimate probabilities of identical-by-descent sharing. CONCLUSIONS: The R
      package GENLIB provides a user friendly and flexible environment to analyze
      extensive genealogical data, allowing an efficient and easy integration of
      different types of data, analytical methods and additional developments and
      making this tool ideal for genealogical analysis.

PMID- 25971992
TI  - Polarity-dependent effects of transcranial direct current stimulation in
      obsessive-compulsive disorder.
AB  - About one third of patients with obsessive-compulsive disorder (OCD) fail to
      experience significant clinical benefit from currently available treatments.
      Hyperactivity of the presupplementary motor area (pre-SMA) has been detected in
      OCD patients, but it is not clear whether it is the primary cause or a secondary
      compensatory mechanism in OCD pathophysiology. Transcranial direct current
      stimulation (tDCS) is a noninvasive brain stimulation technique with polarity
      dependent effects on motor cortical excitability. A 33-year-old woman with
      treatment-resistant OCD received 20 daily consecutive 2 mA/20 min tDCS sessions
      with the active electrode placed on the pre-SMA, according to the 10-20 EEG
      system, and the reference electrode on the right deltoid. The first 10 sessions
      were anodal, while the last 10 were cathodal. Symptoms severity was assessed
      using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) severity score. In the
      end of anodal stimulation, OCD symptoms had worsened. Subsequent cathodal
      stimulation induced a dramatic clinical improvement, which led to an overall 30%
      reduction in baseline symptoms severity score on the Y-BOCS. Our study supports
      the hypothesis that pre-SMA hyperfunction might be responsible for OCD symptoms
      and shows that cathodal inhibitory tDCS over this area might be an option when
      dealing with treatment-resistant OCD.

PMID- 25971993
TI  - Nipro extra-corporeal left ventricular assist device fitting after left
      ventricular reconstruction with mitral valve plasty.
AB  - Both left ventricular assist device and left ventricular reconstruction are
      treatment choices for severe heart failure conditions. Our institution performed
      a left ventricular assist device installation following a left ventricular
      reconstruction procedure on a 42-year-old male patient who presented with dilated
      cardiomyopathy and low cardiac output syndrome. A mitral valve plasty was used to
      correct the acute mitral valve regurgitation and we performed a Nipro extra
      corporeal left ventricular assist device installation on post-operative day 14.
      Due to the left ventricular reconstruction that the patient had in a previous
      operation, we needed to attach an apical cuff on posterior apex, insert the
      inflow cannula with a large curve, and shift the skin insertion site laterally to
      the left. We assessed the angle between the cardiac longitudinal axis and the
      inflow cannula using computed tomography. The patient did not complain of any
      subjective symptoms of heart failure. Although Nipro extra-corporeal left
      ventricular assist device installation after left ventricular reconstruction has
      several difficulties historically, we have experienced a successful case. 

PMID- 25971994
TI  - Feasibility of FDG-PET/CT for the initial diagnosis of papillary thyroid cancer.
AB  - To assess the role of [18F]-fluorodeoxyglucose (FDG) positron emission tomography
      computed tomography (PET/CT) as a preoperative diagnostic tool in papillary
      thyroid carcinoma (PTC). From 2011 to 2014, 197 patients with PTC (246 tumor foci
      in all) underwent FDG-PET. Among these patients, 46 underwent neck dissection for
      lateral neck metastasis. According to the FDG avidity of the tumor foci or
      lateral neck metastasis, factors associated with the prognostic value were
      evaluated by univariate and multivariate logistic regression analyses. Among the
      197 patients, 7 (3.6 %) were incidentally found to have non-thyroid origin
      malignancy. Additionally, 63.0 % (155/246) of PTC foci showed FDG uptake on
      PET/CT. Univariate analysis showed that the tumor size, the presence of
      extrathyroidal extension, BRAF mutation, and Hashimoto thyroiditis were
      associated with FDG avidity. However, except for pathological extrathyroidal
      extension, the other factors showed statistically significant correlations with
      FDG avidity (p < 0.001, p = 0.008, and p = 0.009, respectively). FDG uptake in
      lateral neck node metastasis showed high specificity and negative predictive
      value (NPV). In four cases of nonspecific findings on ultrasonography (USG)/CT,
      FDG avidity was helpful to diagnose the presence of lateral neck metastasis. The
      maximum standardized uptake value (SUVmax) of PET/CT was correlated with the
      maximum diameter of the involved lateral node. FDG avidity did not show any
      significance in the recurrence-free survival of both the thyroid tumor and
      lateral neck metastasis. The FDG avidity of PTC did not show prognostic
      predictive meaning. However, in the case of lateral neck metastasis, FDG avidity
      showed high sensitivity and NPV, and could provide better information in cases of
      nonspecific findings on USG and CT. 

PMID- 25971997
TI  - Erratum for the Research Article: "Prostate cancer cell-stromal cell crosstalk
      via FGFR1 mediates antitumor activity of dovitinib in bone metastases" by X. Wan,
      P. G. Corn, J. Yang, N. Palanisamy, M. W. Starbuck, E. Efstathiou, E. M. Tapia,
      A. J. Zurita, A. Aparicio, M. K. Ravoori, E. S. Vazquez, D. R. Robinson, Y.-M.
      Wu, X. Cao, M. K. Iyer, W. McKeehan, V. Kundra, F. Wang, P. Troncoso, A. M.
      Chinnaiyan, C. J. Logothetis, N. M. Navone.

PMID- 25971996
TI  - Cochlear implantation in patients with inner ear bone malformations with
      posterior labyrinth involvement: an exploratory study.
AB  - Inner ear bone malformations are one cause of profound sensorineural hearing
      loss. This investigation focused on those affecting the posterior labyrinth,
      especially enlarged vestibular aqueduct syndrome, which is associated with
      fluctuating and progressive hearing loss. The objectives of this study were to
      analyze the behavior of the electrical stimulation, auditory functionality and
      linguistic development in patients with inner ear malformations involving the
      posterior labyrinth. The study included ten patients undergoing cochlear
      implantation (cases: five with enlarged vestibular aqueduct, two with vestibular
      aqueduct stenosis/aplasia, and three with semicircular canal disorders). Post
      implantation, data were gathered on the electrical stimulation threshold and
      maximum comfort levels and on the number of functioning electrodes. Evaluation of
      Auditory Responses to Speech (EARS) subtests were used to assess auditory
      functionality and language acquisition at 6, 12, and 24 months post-implantation.
      Results were compared with findings in a control group of 28 cochlear
      implantation patients without these malformations. No significant differences
      were found between case and control groups in electrical stimulation parameters;
      auditory functionality subtest scores were lower in cases than controls, although
      the difference was only statistically significant for some subtests. In
      conclusion, cochlear implantation patients with posterior labyrinth bone
      malformations and profound hearing loss, including those with enlarged vestibular
      aqueduct syndrome, showed no significant difference in electrical stimulation
      threshold with controls. Although some auditory functionality test results were
      lower in cases than in controls, cochlear implantation appears to be beneficial
      for all patients with these malformations.

PMID- 25971998
TI  - Erratum for the Research Article: "Mitigation of tracheobronchomalacia with 3D
      printed personalized medical devices in pediatric patients" by R. J. Morrison, S.
      J. Hollister, M. F. Niedner, M. G. Mahani, A. H. Park, D. K. Mehta, R. G. Ohye,
      G. E. Green.

PMID- 25971995
TI  - The role of PET/CT in the management of patients affected by head and neck
      tumors: a review of the literature.
AB  - The management of head and neck tumor (HNSCC) has been changing over the years,
      especially due to the aid of imaging techniques that help physicians to attain a
      correct diagnosis. These techniques represent a valuable tool to help tailor
      treatment and during follow-up of patients affected by malignancies. The aim of
      this review is to summarize the results of the most recent and relevant studies
      about the use of PET imaging in HNSCCs. This review is divided into six chapters:
      (1) The role of PET/CT in the pre-treatment phase; (2) PET/CT and radiotherapy
      planning; (3) PET/CT in the post-treatment setting; (4) PET/CT and SUVmax for
      prediction of prognosis; (5) miscellanea on the utility of PET in specific
      HNSCCs; (6) non-FDG PET tracers used in HNSCC. Promising results have been
      obtained so far. Despite the encouraging outcomes, more investigations are needed
      to warrant the value of this technique, especially in the pre-treatment setting. 

PMID- 25971999
TI  - How to know when physicians are ready for genomic medicine.
AB  - Despite perceptions to the contrary, physicians are as prepared for genomic
      medicine as they are for other medical innovations; educational initiatives and
      support from genetics specialists can enhance clinical practice. 

PMID- 25972000
TI  - William Heberden and reverse translation.
AB  - Beginning with the 18th-century physician-scientist William Heberden, the elder,
      Science Translational Medicine introduces a new article series about historical
      figures whose transformational contributions to science, medicine, and society
      remain relevant today. 

PMID- 25972001
TI  - Serum microRNAs are early indicators of survival after radiation-induced
      hematopoietic injury.
AB  - Accidental radiation exposure is a threat to human health that necessitates
      effective clinical planning and diagnosis. Minimally invasive biomarkers that can
      predict long-term radiation injury are urgently needed for optimal management
      after a radiation accident. We have identified serum microRNA (miRNA) signatures
      that indicate long-term impact of total body irradiation (TBI) in mice when
      measured within 24 hours of exposure. Impact of TBI on the hematopoietic system
      was systematically assessed to determine a correlation of residual hematopoietic
      stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures
      distinguished untreated mice from animals exposed to radiation and correlated
      with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and
      lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after
      exposure. A serum miRNA signature detectable 24 hours after radiation exposure
      consistently segregated these two cohorts. Furthermore, using either a
      radioprotective agent before, or radiation mitigation after, lethal radiation, we
      determined that the serum miRNA signature correlated with the impact of radiation
      on animal health rather than the radiation dose. Last, using humanized mice that
      had been engrafted with human CD34(+) HSCs, we determined that the serum miRNA
      signature indicated radiation-induced injury to the human bone marrow cells. Our
      data suggest that serum miRNAs can serve as functional dosimeters of radiation,
      representing a potential breakthrough in early assessment of radiation-induced
      hematopoietic damage and timely use of medical countermeasures to mitigate the
      long-term impact of radiation. 

PMID- 25972002
TI  - Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell
      malignancies.
AB  - Bispecific antibodies and antibody fragments in various formats have been
      explored as a means to recruit cytolytic T cells to kill tumor cells. Encouraging
      clinical data have been reported with molecules such as the anti-CD19/CD3
      bispecific T cell engager (BiTE) blinatumomab. However, the clinical use of many
      reported T cell-recruiting bispecific modalities is limited by liabilities
      including unfavorable pharmacokinetics, potential immunogenicity, and
      manufacturing challenges. We describe a B cell-targeting anti-CD20/CD3 T cell
      dependent bispecific antibody (CD20-TDB), which is a full-length, humanized
      immunoglobulin G1 molecule with near-native antibody architecture constructed
      using "knobs-into-holes" technology. CD20-TDB is highly active in killing CD20
      expressing B cells, including primary patient leukemia and lymphoma cells both in
      vitro and in vivo. In cynomolgus monkeys, CD20-TDB potently depletes B cells in
      peripheral blood and lymphoid tissues at a single dose of 1 mg/kg while
      demonstrating pharmacokinetic properties similar to those of conventional
      monoclonal antibodies. CD20-TDB also exhibits activity in vitro and in vivo in
      the presence of competing CD20-targeting antibodies. These data provide rationale
      for the clinical testing of CD20-TDB for the treatment of CD20-expressing B cell
      malignancies. 

PMID- 25972003
TI  - A comprehensive time-course-based multicohort analysis of sepsis and sterile
      inflammation reveals a robust diagnostic gene set.
AB  - Although several dozen studies of gene expression in sepsis have been published,
      distinguishing sepsis from a sterile systemic inflammatory response syndrome
      (SIRS) is still largely up to clinical suspicion. We hypothesized that a
      multicohort analysis of the publicly available sepsis gene expression data sets
      would yield a robust set of genes for distinguishing patients with sepsis from
      patients with sterile inflammation. A comprehensive search for gene expression
      data sets in sepsis identified 27 data sets matching our inclusion criteria. Five
      data sets (n = 663 samples) compared patients with sterile inflammation
      (SIRS/trauma) to time-matched patients with infections. We applied our
      multicohort analysis framework that uses both effect sizes and P values in a
      leave-one-data set-out fashion to these data sets. We identified 11 genes that
      were differentially expressed (false discovery rate <=1%, inter-data set
      heterogeneity P > 0.01, summary effect size >1.5-fold) across all discovery
      cohorts with excellent diagnostic power [mean area under the receiver operating
      characteristic curve (AUC), 0.87; range, 0.7 to 0.98]. We then validated these 11
      genes in 15 independent cohorts comparing (i) time-matched infected versus
      noninfected trauma patients (4 cohorts), (ii) ICU/trauma patients with infections
      over the clinical time course (3 cohorts), and (iii) healthy subjects versus
      sepsis patients (8 cohorts). In the discovery Glue Grant cohort, SIRS plus the 11
      gene set improved prediction of infection (compared to SIRS alone) with a
      continuous net reclassification index of 0.90. Overall, multicohort analysis of
      time-matched cohorts yielded 11 genes that robustly distinguish sterile
      inflammation from infectious inflammation. 

PMID- 25972005
TI  - Classic reaction kinetics can explain complex patterns of antibiotic action.
AB  - Finding optimal dosing strategies for treating bacterial infections is extremely
      difficult, and improving therapy requires costly and time-intensive experiments.
      To date, an incomplete mechanistic understanding of drug effects has limited our
      ability to make accurate quantitative predictions of drug-mediated bacterial
      killing and impeded the rational design of antibiotic treatment strategies. Three
      poorly understood phenomena complicate predictions of antibiotic activity: post
      antibiotic growth suppression, density-dependent antibiotic effects, and
      persister cell formation. We show that chemical binding kinetics alone are
      sufficient to explain these three phenomena, using single-cell data and time-kill
      curves of Escherichia coli and Vibrio cholerae exposed to a variety of
      antibiotics in combination with a theoretical model that links chemical reaction
      kinetics to bacterial population biology. Our model reproduces existing
      observations, has a high predictive power across different experimental setups
      (R(2) = 0.86), and makes several testable predictions, which we verified in new
      experiments and by analyzing published data from a clinical trial on tuberculosis
      therapy. Although a variety of biological mechanisms have previously been invoked
      to explain post-antibiotic growth suppression, density-dependent antibiotic
      effects, and especially persister cell formation, our findings reveal that a
      simple model that considers only binding kinetics provides a parsimonious and
      unifying explanation for these three complex, phenotypically distinct behaviours.
      Current antibiotic and other chemotherapeutic regimens are often based on trial
      and error or expert opinion. Our "chemical reaction kinetics"-based approach may
      inform new strategies, which are based on rational design. 

PMID- 25972004
TI  - The nicotinic alpha6 subunit gene determines variability in chronic pain
      sensitivity via cross-inhibition of P2X2/3 receptors.
AB  - Chronic pain is a highly prevalent and poorly managed human health problem. We
      used microarray-based expression genomics in 25 inbred mouse strains to identify
      dorsal root ganglion (DRG)-expressed genetic contributors to mechanical
      allodynia, a prominent symptom of chronic pain. We identified expression levels
      of Chrna6, which encodes the alpha6 subunit of the nicotinic acetylcholine
      receptor (nAChR), as highly associated with allodynia. We confirmed the
      importance of alpha6* (alpha6-containing) nAChRs by analyzing both gain- and loss
      of-function mutants. We find that mechanical allodynia associated with
      neuropathic and inflammatory injuries is significantly altered in alpha6*
      mutants, and that alpha6* but not alpha4* nicotinic receptors are absolutely
      required for peripheral and/or spinal nicotine analgesia. Furthermore, we show
      that Chrna6's role in analgesia is at least partially due to direct interaction
      and cross-inhibition of alpha6* nAChRs with P2X2/3 receptors in DRG nociceptors.
      Finally, we establish the relevance of our results to humans by the observation
      of genetic association in patients suffering from chronic postsurgical and
      temporomandibular pain. 

PMID- 25972006
TI  - Functional inflammatory profiles distinguish myelin-reactive T cells from
      patients with multiple sclerosis.
AB  - Myelin-reactive T cells have been identified in patients with multiple sclerosis
      (MS) and healthy subjects with comparable frequencies, but the contribution of
      these autoreactive T cells to disease pathology remains unknown. A total of
      13,324 T cell libraries generated from blood of 23 patients and 22 healthy
      controls were interrogated for reactivity to myelin antigens. Libraries derived
      from CCR6(+) myelin-reactive T cells from patients with MS exhibited
      significantly enhanced production of interferon-gamma (IFN-gamma), interleukin-17
      (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared
      to healthy controls. Single-cell clones isolated by major histocompatibility
      complex/peptide tetramers from CCR6(+) T cell libraries also secreted more
      proinflammatory cytokines, whereas clones isolated from controls secreted more IL
      10. The transcriptomes of myelin-specific CCR6(+) T cells from patients with MS
      were distinct from those derived from healthy controls and, notably, were
      enriched in T helper cell 17 (TH17)-induced experimental autoimmune encephalitis
      gene signatures, and gene signatures derived from TH17 cells isolated other human
      autoimmune diseases. These data, although not causal, imply that functional
      differences between antigen-specific T cells from MS and healthy controls are
      fundamental to disease development and support the notion that IL-10 production
      from myelin-reactive T cells may act to limit disease progression or even
      pathogenesis. 

PMID- 25972007
TI  - Local health practices and the knowledge of medicinal plants in a Brazilian semi
      arid region: environmental benefits to human health.
AB  - BACKGROUND: The concept of eco-cultural health considers the dynamic interaction
      between humans and ecosystems, emphasizing the implications of the health of the
      ecosystem for the health and well-being of human populations. Ethnobotanical
      studies focusing on folk medicine and medicinal plants can contribute to the
      field of eco-cultural health if they incorporate the perspective and local
      knowledge of communities. We investigated the local health practices in three
      rural communities living within the vicinity of a protected area of sustainable
      use in a semi-arid region of Brazil. We analyzed the opinions of local health
      experts on the elements that influence human health and on how the environment
      contributes to this influence. We also analyzed and compared the local knowledge
      of medicinal plants, as knowledge of this type is an important factor when
      considering the interaction between environmental and human health. METHODS: We
      performed structured interviews and free-listings with 66 local health experts.
      We used content analysis to systematize the elements of the influences on human
      health. We compared the richness of the plants cited among communities and
      analyzed the differences among the three communities regarding the ways in which
      the plants were obtained and the environments in which plants were collected.
      RESULTS: The local experts identified several influences of the environment on
      human health. These influences can be associated with ecosystem services, such as
      climatic conditions, water and air quality, recreation and medicinal and food
      resources. We identified 192 medicinal plant species, most of which were gathered
      from wild ecosystems. The most important environments for the three communities
      were the plateau mountain and backyards. CONCLUSIONS: The informants had a broad
      and integrated view of health, perceiving the importance of conserving the
      environment within the National Forest of Araripe for the health and well-being
      of the local populations.

PMID- 25972008
TI  - Crystal Structure and Product Analysis of an Archaeal myo-Inositol Kinase Reveal
      Substrate Recognition Mode and 3-OH Phosphorylation.
AB  - The TK2285 protein from Thermococcus kodakarensis was recently characterized as
      an enzyme catalyzing the phosphorylation of myo-inositol. Only two myo-inositol
      kinases have been identified so far, the TK2285 protein and Lpa3 from Zea mays,
      both of which belong to the ribokinase family. In either case, which of the six
      hydroxyl groups of myo-inositol is phosphorylated is still unknown. In addition,
      little is known about the myo-inositol binding mechanism of these enzymes. In
      this work, we determined two crystal structures: those of the TK2285 protein
      complexed with the substrates (ATP analogue and myo-inositol) or the reaction
      products formed by the enzyme. Analysis of the ternary substrates-complex
      structure and site-directed mutagenesis showed that five residues were involved
      in the interaction with myo-inositol. Structural comparison with other ribokinase
      family enzymes indicated that two of the five residues, Q136 and R140, are
      characteristic of myo-inositol kinase. The crystal structure of the ternary
      products-complex, which was prepared by incubating the TK2285 protein with myo
      inositol and ATP, holds 1d-myo-inositol 3-phosphate (Ins(3)P) in the active site.
      NMR and HPLC analyses with a chiral column also indicated that the TK2285
      reaction product was Ins(3)P. The results obtained here showed that the TK2285
      protein specifically catalyzes the phosphorylation of the 3-OH of myo-inositol.
      We thus designated TK2285 as myo-inositol 3-kinase (MI3K). The precise
      identification of the reaction product should provide a sound basis to further
      explore inositol metabolism in Archaea. 

PMID- 25972009
TI  - "Disk extension beyond the interspace": an investigation into an alternative
      nomenclature in diagnostic imaging for displaced canine intervertebral disk
      material.
AB  - BACKGROUND: Displacement of canine intervertebral disk material can be seen
      directly in diagnostic imaging modalities such as magnetic resonance imaging and
      computed tomographic imaging. Canine intervertebral disk herniation can be
      differentiated into Hansen type 1 and 2 categories by clinical appearance, but
      anular- and nuclear disk material cannot be distinguished in computed tomographic
      images. Therefore, we hypothesized that the "Disk extension beyond the
      interspace"-nomenclature that describes the displacement by the disk contour
      might aid diagnosis. The aim of this study was to test the reliability of the
      "Disk extension beyond the interspace"-nomenclature in the evaluation of canine
      intervertebral disks via magnetic resonance and computed tomographic imaging.
      RESULTS: Magnetic resonance and computed tomographic images of 144 intervertebral
      disks of 43 dogs were evaluated by 3 observers with different degrees of
      experience from 2 institutions retrospectively. A substantial intraobserver
      agreement was found, while interobserver agreement was fair to moderate with
      significant differences in evaluation. Comparison of imaging methods showed a
      fair to moderate agreement without statistically significant differences in
      evaluation. CONCLUSIONS: DEBIT-nomenclature cannot be recommended for veterinary
      clinical usage yet. The largest variability was found in the evaluation of the
      bulged canine intervertebral disk. The observers' experience and the imaging
      method influenced DEBIT- evaluation only slightly, while training and working at
      different institutions influenced DEBIT-evaluation strongly.

PMID- 25972010
TI  - Ovodefensins, an Oviduct-Specific Antimicrobial Gene Family, Have Evolved in
      Birds and Reptiles to Protect the Egg by Both Sequence and Intra-Six-Cysteine
      Sequence Motif Spacing.
AB  - Ovodefensins are a novel beta defensin-related family of antimicrobial peptides
      containing conserved glycine and six cysteine residues. Originally thought to be
      restricted to the albumen-producing region of the avian oviduct, expression was
      found in chicken, turkey, duck, and zebra finch in large quantities in many parts
      of the oviduct, but this varied between species and between gene forms in the
      same species. Using new search strategies, the ovodefensin family now has 35
      members, including reptiles, but no representatives outside birds and reptiles
      have been found. Analysis of their evolution shows that ovodefensins divide into
      six groups based on the intra-cysteine amino acid spacing, representing a unique
      mechanism alongside traditional evolution of sequence. The groups have been used
      to base a nomenclature for the family. Antimicrobial activity for three
      ovodefensins from chicken and duck was confirmed against Escherichia coli and a
      pathogenic E. coli strain as well as a Gram-positive organism, Staphylococcus
      aureus, for the first time. However, activity varied greatly between peptides,
      with Gallus gallus OvoDA1 being the most potent, suggesting a link with the
      different structures. Expression of Gallus gallus OvoDA1 (gallin) in the oviduct
      was increased by estrogen and progesterone and in the reproductive state.
      Overall, the results support the hypothesis that ovodefensins evolved to protect
      the egg, but they are not necessarily restricted to the egg white. Therefore,
      divergent motif structure and sequence present an interesting area of research
      for antimicrobial peptide design and understanding protection of the cleidoic
      egg. 

PMID- 25972011
TI  - The Ovarian Antral Follicle: Living on the Edge of Hypoxia or Not?
AB  - Oocytes within antral follicles are thought to have restricted access to O2, as
      follicle vascularity is not adjacent and both granulosa and cumulus cells are
      metabolically active. Indeed, measured follicular antrum partial pressure (pO2)
      is regarded as low, but accurate and direct measurement represents a technical
      challenge that has yet to be overcome. The oocyte itself is highly dependent on
      oxidative phosphorylation for survival and competence for further development
      following fertilization, and it has been suggested that follicular pO2 levels are
      correlated with this capacity for further development. It is clear that
      gonadotropins are involved in regulating antrum formation, follicle
      vascularization, cellular differentiation, and the hypoxia-inducible factors
      (HIF), which are mainly regulated by dissolved O2 concentration. A newly
      discovered player in this story is the intracellular production of hemoglobin by
      both granulosa and cumulus cells, as well as the oocyte. Furthermore, cellular
      hemoglobin levels are dynamic, responding to the ovulatory luteinizing hormone
      (LH) surge. We hypothesize that this gas transport and antioxidant molecule is
      involved in the prevention of hypoxic response signaling by HIFs within the
      preovulatory antral follicle; and the transition of granulosa cells to luteal
      tissue by facilitating the stabilization of HIFs, enabling induction of
      luteinization signaling. Another possible role is by sequestering nitric oxide
      (NO) during the ovulatory period, which may facilitate the resumption of meiosis
      in the oocyte. Testing these hypotheses will be challenging but important if the
      regulation of ovarian function is to be fully understood. 

PMID- 25972012
TI  - Association of Egg Mass and Egg Sex: Gene Expression Analysis from Maternal RNA
      in the Germinal Disc Region of Layer Hens (Gallus gallus).
AB  - Female birds have been shown to manipulate offspring sex ratio. However,
      mechanisms of sex ratio bias are not well understood. Reduced feed availability
      and change in body condition can affect the mass of eggs in birds that could lead
      to a skew in sex ratio. We employed feed restriction in laying chickens (Gallus
      gallus) to induce a decrease in body condition and egg mass using 45 chicken hens
      in treatment and control groups. Feed restriction led to an overall decline of
      egg mass. In the second period of treatment (Days 9-18) with more severe feed
      restriction and a steeper decline of egg mass, the sex ratio per hen (proportion
      of male eggs) had a significant negative association with mean egg mass per hen.
      Based on this association, two groups of hens were selected from feed restriction
      group, that is, hens producing male bias with low egg mass and hens producing
      female bias with high egg mass with overall sex ratios of 0.71 and 0.44
      respectively. Genomewide transcriptome analysis on the germinal disks of F1
      preovulatory follicles collected at the time of occurrence of meiosis-I was
      performed. We did not find significantly differentially expressed genes in these
      two groups of hens. However, gene set enrichment analysis showed that a number of
      cellular processes related to cell cycle progression, mitotic/meiotic apparatus,
      and chromosomal movement were enriched in female-biased hens or high mean egg
      mass as compared with male-biased hens or low mean egg mass. The differentially
      expressed gene sets may be involved in meiotic drive regulating sex ratio in the
      chicken. 

PMID- 25972013
TI  - Enalapril Normalizes Endothelium-Derived Hyperpolarizing Factor-Mediated
      Relaxation in Mesenteric Artery of Adult Hypertensive Rats Prenatally Exposed to
      Testosterone.
AB  - Prenatal exposure to elevated testosterone levels induces adult life hypertension
      associated with selective impairments in endothelium-derived hyperpolarizing
      factor (EDHF)-mediated relaxation in mesenteric arteries. We tested whether the
      angiotensin-converting enzyme inhibitor enalapril restores EDHF function through
      regulating the activities of small (Kcnn3) and intermediate (Kcnn4) conductance
      calcium-activated potassium channels in mesenteric arteries. Pregnant Sprague
      Dawley rats were injected subcutaneously with vehicle or testosterone propionate
      (0.5 mg/kg/day from Gestation Day 15 to 19), and their 6-mo-old adult male
      offspring were examined. A subset of rats in these two groups was given enalapril
      (40 mg/kg/day) for 2 wk through drinking water. Blood pressures were assessed
      through carotid arterial catheter and endothelium-dependent mesenteric arterial
      EDHF relaxation, using wire myography. Ace and Kcnn3 and Kcnn4 channel expression
      levels were also examined. Renal and vascular Ace expression and plasma
      angiotensin II levels were increased in testosterone offspring. Blood pressure
      levels were significantly higher in testosterone offspring than in controls, and
      treatment with enalapril significantly attenuated blood pressure in testosterone
      offspring. EDHF relaxation in testosterone offspring was reduced compared to that
      in controls, and it was significantly restored by enalapril treatment. Kcnn4
      channel expression and function were similar between control and testosterone
      rats, but it was not affected by enalapril treatment. Relaxation mediated by
      Kcnn3 was impaired in testosterone offspring, and it was normalized by enalapril
      treatment. Furthermore, enalapril treatment restored expression levels of Kcnn3
      channels. These findings suggest that enalapril has a positive influence on
      endothelial function with improvement in EDHF relaxation through normalization of
      Kcnn3 expression and activity. 

PMID- 25972014
TI  - Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the
      Heart from Ischemic Injury in Female Rats.
AB  - Previous studies have shown that female offspring are resistant to fetal stress
      induced programming of ischemic-sensitive phenotype in the heart; however, the
      mechanisms responsible remain unclear. The present study tested the hypothesis
      that estrogen plays a role in protecting females in fetal programming of
      increased heart vulnerability. Pregnant rats were divided into normoxic and
      hypoxic (10.5% O2 from Day 15 to 21 of gestation) groups. Ovariectomy (OVX) and
      estrogen (E2) replacement were performed in 8-wk-old female offspring. Hearts of
      4-mo-old females were subjected to ischemia and reperfusion injury in a
      Langendorff preparation. OVX significantly decreased postischemic recovery of
      left ventricular function and increased myocardial infarction, and no difference
      was observed between normoxic and hypoxic groups. The effect of OVX was rescued
      by E2 replacement. OVX decreased the binding of glucocorticoid receptor (GR) to
      glucocorticoid response elements at angiotensin II type 1 (Agtr1) and type 2
      (Agtr2) receptor promoters, resulting in a decrease in Agtr1 and an increase in
      Agtr2 in the heart. Additionally, OVX decreased estrogen receptor (ER) expression
      in the heart and inhibited ER/GR interaction in binding to glucocorticoid
      response elements at the promoters. Consistent with the changes in Agtrs, OVX
      significantly decreased Prkce abundance in the heart. These OVX-induced changes
      were abrogated by E2 replacement. The results indicate that estrogen is not
      directly responsible for the sex dimorphism in fetal programming of heart
      ischemic vulnerability but suggest a novel mechanism of estrogen in regulating
      cardiac Agtr1/Agtr2 expression patterns and protecting female hearts against
      ischemia and reperfusion injury. 

PMID- 25972015
TI  - Activation of Adenosine Monophosphate-Activated Protein Kinase Is an Additional
      Mechanism That Participates in Mediating Inhibitory Actions of Prostaglandin
      F2Alpha in Mature, but Not Developing, Bovine Corpora Lutea.
AB  - Elevated cytosolic calcium and protein kinase C are well-established mediators of
      luteolytic actions of prostaglandin F2alpha (PGF2alpha). The objectives of this
      study were to determine 1) if calcium/calmodulin-dependent kinase kinase 2
      (CAMKK2) participates in mediating PGF2alpha actions in developing (Day [d]-4)
      and mature (d-10) bovine corpus luteum (CL), 2) distal targets of CAMKK2, 3)
      developmental expression of adenosine monophosphate-activated protein kinase
      (AMPK), and 4) effects of AMPK activation on progesterone (P4) production.
      Expression of AMPK increased as the CL matured. Activation of the prostaglandin
      receptor (FP) induced rapid phosphorylation of AMPK, which was blocked by a
      CAMKK2 inhibitor. Changes in basal P4 secretion in vitro were determined in
      response to AMPK activation via metformin (met) or 5-aminoimidazole-4-carboxamide
      ribonucleotide (AICAR) in d-4 and d-10 CL. Production of P4 in d-10 CL decreased
      with met or AICAR compared to control, similar to activation by PGF2alpha.
      Therefore, potential distal targets of AMPK in d-10 CL were examined during
      induced functional regression via exogenous PGF2alpha. Serum and luteal P4
      decreased at 2 and 4 h after administration of PGF2alpha. Protein expression of
      LDLR decreased at 2 and 4 h, while those of ACAT1 and STAR increased 4 h after
      PGF2alpha. During induced regression, alterations of cholesterol transport
      proteins contributed to decreased luteal and serum P4. Therefore, developmental
      differences in signal transduction associated with FP, specifically CAMKK2 and
      AMPK, partially contribute to differences in the ability of PGF2alpha to induce
      regression in mature, but not developing, bovine CL. Multiple cholesterol
      transport proteins, including LDLR, were altered by PGF2alpha and could be
      potential AMPK targets.

PMID- 25972016
TI  - Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results
      in Impaired Male Fertility in Mice.
AB  - The reproductive homeobox X-linked, Rhox, genes encode transcription factors that
      are selectively expressed in reproductive tissues. While there are 33 Rhox genes
      in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they
      may regulate the expression of somatic-cell gene products crucial for germ cell
      development. We previously characterized Rhox5-null mice, which are subfertile,
      exhibiting excessive germ cell apoptosis and compromised sperm motility. To
      assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi
      approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to
      drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western
      and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8.
      However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression
      patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8
      knockdown animals showed significantly reduced spermatogenic output, increased
      germ cell apoptosis, and compromised sperm motility, leading to impaired
      fertility. Importantly, our results revealed that while some RHOX5-dependent
      factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the
      majority were not, and novel putative RHOX8-regulated genes were identified. This
      suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells
      elicits similar phenotypes, these genes are not entirely redundant. Taken
      together, our study underscores the importance of Rhox genes in male fertility
      and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical
      for complete male fertility. 

PMID- 25972017
TI  - Hypertensive crisis caused by electrocauterization of the adrenal gland during
      hepatectomy.
AB  - BACKGROUND: Hypertensive crisis (i.e., systolic blood pressure over 300 mmHg) is
      very rare during operation except pheochromocytoma, but it can be a fatal and
      embarrassing to surgeons and anesthesiologists. The right adrenal gland can be
      electrocauterized during a right hemi-hepatectomy. We report a case of
      hypertensive crisis during right hemi-hepatectomy in which the right adrenal
      gland was stimulated by monopolar electrocautery in a patient with normal
      neuroendocrine function. CASE PRESENTATION: A 73-year-old man with hepatocellular
      carcinoma was scheduled to undergo right hemi-hepatectomy. Three hours into the
      surgery, the patient's blood pressure increased abruptly from 100/40 to over
      350/130 mmHg (the maximum measurement pressure of the monitor; 350 mmHg). The
      surgeon had cauterized the right adrenal gland using monopolar electrocautery to
      separate the liver from the adrenal gland immediately prior to the event.
      Approximately 3 minutes after suspending the operation, blood pressure returned
      to baseline levels. After the event, the operation was successfully completed
      without any complication. Hormonal studies and iodine-123 meta
      iodobenzylguanidine scintigraphy revealed no neuroendocrine tumor such as a
      pheochromocytoma. CONCLUSION: Operations such as hepatectomy that stimulate the
      adrenal gland may lead to an unexpected catecholamine surge and result in
      hypertensive crisis, even if neuroendocrine function of the adrenal gland is
      normal.

PMID- 25972018
TI  - Effect of laser acupuncture on obesity: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Obesity-related diseases have a profound economic impact on health
      care systems. Laser acupuncture has been shown to have beneficial effects on
      obesity. However, to our knowledge, those trials were either non-randomized, non
      blinded or included low-calorie diet control. We have, therefore, designed a
      patient-assessor-blinded, randomized, sham-controlled crossover trial to
      investigate the significance of laser acupuncture on obesity. METHODS/DESIGN: 104
      subjects above 20 years of age with a body mass index (BMI) of over 25 kg/m(2)
      will be divided into 2 groups: experimental and control. Each subject will
      receive the treatment relevant to their group 3 times a week for 8 weeks. After 8
      weeks of treatment the subject will enter a 2-week washout period, after which
      the subjects will switch groups. Measurements will include BMI, body fat
      percentage, waist-to-hip ratio (WHR), waist circumference, hip circumference,
      skinfold thickness, thigh circumference, body fat, blood pressure, heart rate,
      hunger and the 36-item Short-Form Health Survey (SF-36). DISCUSSION: The results
      of this study will provide the basis for future large-scale multicenter trials
      investigating the effects of laser acupuncture on obesity. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02167308 ; registration date: 14 June 2014.

PMID- 25972019
TI  - Cell viability evaluation of transdifferentiated endothelial-like cells by
      quantitative electron-probe X-ray microanalysis for tissue engineering.
AB  - Development of an efficient vascular substitute by tissue engineering is strongly
      dependent on endothelial cell viability. The aim of this study was to evaluate
      cell viability of transdifferentiated endothelial-like cells (Tr-ELC) by using
      for the first time electron probe X-ray microanalysis (EPXMA), not only to
      accurately analyze cell viability by quantifying the intracellular ionic
      concentrations, but also to establish their possible use in vascular tissue
      engineering protocols. Human umbilical cord Wharton's jelly stem cells (HWJSC)
      and endothelial cells from the human umbilical vein (HUVEC) were isolated and
      cultured. Transdifferentiation from HWJSC to the endothelial phenotype was
      induced. EPXMA was carried out to analyze HUVEC, HWJSC and Tr-ELC cells by using
      a scanning electron microscope equipped with an EDAX DX-4 microanalytical system
      and a solid-state backscattered electron detector. To determine total ion
      content, the peak-to-local-background (P/B) ratio method was used with reference
      to standards composed of dextran containing known amounts of inorganic salts. Our
      results revealed a high K/Na ratio in Tr-ELC (9.41), in association with the
      maintenance of the intracellular levels of chlorine, phosphorous and magnesium
      and an increase of calcium (p=0.031) and sulfur (p=0.022) as compared to HWJSC.
      Calcium levels were similar for HUVEC and Tr-ELC. These results ensure that
      transdifferentiated cells are highly viable and resemble the phenotypic and
      microanalytical profile of endothelial cells. Tr-ELC induced from HWJSC may
      fulfill the requirements for use in tissue engineering protocols applied to the
      vascular system at the viability and microanalytical levels. 

PMID- 25972020
TI  - Optically tunable chiral nematic mesoporous cellulose films.
AB  - Demand for sustainable functional materials has never been larger. The
      introduction of functionality into pure cellulose might be one step forward in
      this field as it is one of the most abundant natural biopolymers. In this paper,
      we demonstrate a straightforward and scalable way to produce iridescent,
      mesoporous cellulose membranes with tunable colors and porosity. Concomitant
      assembly of cellulose nanocrystals (CNCs) and condensation of silica precursors
      results in CNC-silica composites with chiral nematic structures and tunable
      optical properties. Removal of the stabilizing silica matrix by alkaline or acid
      treatment gives access to novel chiral nematic mesoporous cellulose (CNMC) films.
      Importantly, the optical properties and the mesoporosity can be controlled by
      either varying the silica-to-CNC ratio, or by varying the substrate used during
      the evaporation-induced self-assembly process. In order to introduce additional
      functionality, CNMC has been used to stabilize gold nanoparticles with three
      different concentrations by wet impregnation. These materials are stable in water
      and can potentially function in sensors, tissue engineering or functional
      membranes. 

PMID- 25972021
TI  - Editorial Commentary: The Story of Sisyphus: Why We Need a Universal Pneumococcal
      Vaccine to Replace Current Conjugate Vaccines.

PMID- 25972022
TI  - Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis
      in US Children.
AB  - BACKGROUND: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on
      pneumococcal meningitis (PM) in US children is unknown. We compared the serotype
      distribution, antibiotic susceptibility, hospital course, and outcomes of
      children with PM 3 years before and 3 years after the introduction of PCV13.
      METHODS: We identified patients <= 18 years of age with PM at 8 children's
      hospitals in the United States. Pneumococcal isolates were collected
      prospectively. Serotyping and antibiotic susceptibility were performed in a
      central laboratory. Clinical data were abstracted from medical records. Patients
      were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010),
      and post-PCV13 (2011-2013). Categorical variables were analyzed by the chi(2)
      test and continuous variables by the Mann--Whitney U test. RESULTS: During the
      study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were
      identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%)
      during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases
      decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13
      serotype cases represented 73% of the isolates in 2011-2013. Isolates with
      ceftriaxone minimum inhibitory concentration >= 1 ug/mL decreased (13% to 3%)
      from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified
      for hospital course or outcome, with the exception that a greater proportion of
      patients had subdural empyema and hemiparesis in 2011-2013. CONCLUSIONS: After
      the introduction of PCV13, the number of cases of PM in children remained
      unchanged compared with 2007-2009, although the proportion of PCV13 serotypes
      decreased significantly. Serotype 19A continued to be the most common serotype in
      2011-2013. Antibiotic resistance decreased significantly. Morbidity and case
      fatality rate due to PM remain substantial.

PMID- 25972023
TI  - Editorial Commentary: Pseudomonas aeruginosa Eradication: How Do We Measure
      Success?

PMID- 25972025
TI  - Adhesive Forces between A1 Domain of von Willebrand Factor and N-terminus Domain
      of Glycoprotein Ibalpha Measured by Atomic Force Microscopy.
AB  - AIM: von Willebrand factor (VWF) plays an important role in the regulation of
      hemostasis and thrombosis formation, particularly under a high shear rate.
      However, the adhesive force due to the molecular interaction between VWF and
      glycoprotein Ibalpha (GPIbalpha) has not been fully explored. Thus, we employed
      atomic force microscopy to directly measure the adhesive force between VWF and
      GPIbalpha. METHODS: We measured the adhesive force between VWF and GPIbalpha at
      the molecular level using an atomic force microscope (AFM). An AFM cantilever was
      coated with recombinant N-terminus VWF binding site of GPIbalpha, whereas a cover
      glass was coated with native VWF. RESULTS: The adhesive force at the molecular
      level was measured using an AFM. In the presence of 1 MUg/mL VWF, the adhesion
      force was nearly 200 pN. As per the Gaussian fit analysis, the adhesive force of
      a single bond could have been 54 or 107 pN. CONCLUSION: Our consideration with
      the Gaussian fit analysis proposed that the adhesive force of a single bond could
      be 54 pN, which is very close to that obtained by optical tweezers (50 pN).

PMID- 25972024
TI  - Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long
      term Outcomes in Cystic Fibrosis.
AB  - BACKGROUND: Pseudomonas aeruginosa (Pa) is the most important pathogen infecting
      the airways in individuals with cystic fibrosis. A key question is whether
      children with newly acquired Pa infection who are able to achieve sustained
      eradication after early antipseudomonal therapy demonstrate improved long-term
      health outcomes compared with those who are unable to achieve a sustained
      microbiologic response. METHODS: This cohort study utilized observational follow
      up data on children participating in the Early Pseudomonas Infection Control
      trial who received standardized therapy for newly acquired Pa. Sustained
      eradicators were defined as those who maintained Pa-negative cultures for 12
      months after initial antipseudomonal therapy. Associations between eradication
      status and outcomes were assessed. RESULTS: Of the 249 trial participants
      included in the study, 172 (69%) achieved sustained eradication of Pa during the
      trial (sustained eradicators). Over the median 5-year follow-up, sustained
      eradicators had a 74% reduced risk of developing chronic Pa (hazard ratio [HR],
      0.26; 95% confidence interval [CI], .17-.40) and a 57% reduced risk of mucoidy
      (HR, 0.43; 95% CI, .25-.73) compared with nonsustained eradicators. Sustained
      eradicators had significantly less anti-Pa antibiotic usage during follow-up
      compared with nonsustained eradicators. There was no association between
      eradication status and clinical outcomes including rate of exacerbation and lung
      function decline. CONCLUSIONS: This is the first study to quantify the long-term
      durability of microbiological response associated with early antipseudomonal
      therapy, demonstrating the critical importance of optimizing antipseudomonal
      therapies during early Pa infection. The clinical impact of failure to achieve
      sustained Pa eradication remains unclear, however, and may be confounded by anti
      Pa antibiotic usage. CLINICAL TRIALS REGISTRATION: NCT00097773.

PMID- 25972026
TI  - Venous status ulcers due to congenital agenesis of the inferior vena cava in a 16
      year-old male.
AB  - We report a case of agenesis of the infrarenal inferior vena cava in a 16-year
      old male presenting with venous stasis dermatitis and ulceration in the gaiter
      region bilaterally. Duplex imaging was performed revealing absence of infrarenal
      inferior vena cava and iliofemoral venous system. Magnetic resonance venography
      then confirmed the above findings along with revealing extensive lumbar and
      pelvic collateralization. This patient's condition has been successfully managed
      conservatively with compression therapy and wound care. This case is a rare
      example of a congenital malformation of the inferior vena cava and represents the
      only reported case with presenting symptoms of venous stasis ulceration in a
      pediatric patient. 

PMID- 25972027
TI  - Ureteroarterial fistula: A review of the literature.
AB  - Ureteroarterial fistulas are rare, erosive defects that occur between the distal
      segments of the ureter and the adjacent blood vessels in individuals with
      urologic and vascular comorbidities. Characterized by diffuse, pulsatile bleeding
      into the urinary tract, this condition carries a significant mortality rate in
      the absence of early recognition. Recent treatment efforts have focused on use of
      endovascular stenting techniques as an alternative to open surgical closure of
      the underlying defects in hemodynamically stable patients. We provide a
      literature review detailing the characteristics, mechanism, and management of
      ureteroarterial fistulas. 

PMID- 25972028
TI  - Endovenous laser ablation of insufficient perforating veins: Energy is key to
      success.
AB  - OBJECTIVE: To evaluate the feasibility and anatomical success of endovenous laser
      ablation (EVLA) of incompetent perforating veins (IPV). METHODS: All 135
      consecutive patients with IPV treated with ELVA (intention-to-treat) from January
      2008 to December 2013 were included. Up to the end of 2011, an 810-nm laserset
      (14 W) was used, and afterwards, a 1470-nm laserset (6 W) was introduced. Duplex
      ultrasound was performed at 6 weeks' follow-up to assess anatomical success.
      RESULTS: Overall anatomical success at 6 weeks' follow-up was 56%. Anatomical
      success was 63% after treatment with 810 nm and 45% with 1470 nm (p = 0.035).
      This difference in the success rate seems associated with the significantly
      higher amount of energy delivered in the 810 nm cohort (560 J) versus 1470 nm
      (186 J). Regardless of the type of laser, anatomical success was significantly
      higher after treatment with more than 400 J (66%) compared with 0-200 J (40%, p =
      0.009) and 200-400 J (43%, p = 0.029). Complications were limited to two cases of
      transient paresthesia. CONCLUSIONS: EVLA of IPVs is safe and feasible. The amount
      of energy is highly important in achieving anatomical success.

PMID- 25972029
TI  - Computation of blood flow through collateral circulation of the superficial
      femoral artery.
AB  - OBJECTIVE: Obliteration of collaterals during (endo)vascular treatment of
      peripheral arterial occlusive disease is considered detrimental. We use a model
      to calculate maximum collateral bed flow of the superficial femoral artery in
      order to provide insight in their hemodynamic relevance. METHOD: A computational
      model was developed using digital subtraction angiographies in combination with
      Poiseuille's equation and Ohm's law. Lesions were divided into short and long
      (<15 cm and >=15 cm, respectively) and into stenosis and occlusions. Data are
      presented in relation to the calculated maximum healthy superficial femoral
      artery flow. RESULTS: Stenotic lesions are longer than occlusive lesions (P <
      0.05) and occlusions had more and larger collaterals (P < 0.05). In all four
      study groups the collateral flow significantly increased the total flow (P <
      0.05). The maximum collateral system flow in the stenosis and occlusion groups
      was 5.1% and 20.8% of healthy superficial femoral artery flow, respectively (P <
      0.05), and there were no significant differences between short and long lesions
      (11.2% and 6.7% of healthy superficial femoral artery flow, respectively).
      CONCLUSION: The maximum collateral system flow of the superficial femoral artery
      is only a fraction, with a maximum of one fifth, of healthy superficial femoral
      artery flow. Effects of collateral vessel occlusion during (endo)vascular
      treatment may therefore be without detrimental consequences.

PMID- 25972030
TI  - Long-term outcomes and factors influencing late survival following elective
      abdominal aortic aneurysm repair: A 24-year experience.
AB  - BACKGROUND: Abdominal aortic aneurysms can be either treated by an open abdominal
      aortic aneurysm repair or an endovascular repair. Comparing clinical predictors
      of outcomes and those which influence survival rates in the long term is
      important in determining the choice of treatment offered and the decision-making
      process with patients. AIMS: To determine the influence of pre-existing clinical
      predictors and perioperative determinants on late survival of elective open
      abdominal aortic aneurysm repair and endovascular repair at a tertiary hospital.
      METHODS: Consecutive patients undergoing elective abdominal aortic aneurysm
      repair from 1990 to 2013 were included. Data were collected from a prospectively
      acquired database and death data were gathered from the Queensland state death
      registry. Pre-existing risks and perioperative factors were assessed
      independently. Kaplan-Meier and Cox regression modeling were performed. RESULTS:
      During the study period, 1340 abdominal aortic aneurysms were repaired
      electively, of which 982 were open abdominal aortic aneurysm repair. The average
      age was 72.4 years old and 81.7% were males. The cumulative percentage survival
      rates for open abdominal aortic aneurysms repair at 5, 10, 15 and 20 years were
      79, 49, 31 and 22, respectively. The corresponding 5-, 10- and 15-year survival
      rates for endovascular repair were not significantly different at 75, 49 and 33%,
      respectively (P = 0.75). Predictors of reduced survival were advanced age,
      American Society of Anaesthesiology scores, chronic obstructive pulmonary
      disease, renal impairment, bifurcated grafts, peripheral vascular disease and
      congestive heart failure. CONCLUSIONS: Open repair offers a good long-term
      treatment option for patients with an abdominal aortic aneurysm and in our
      experience there is no significant difference in late survival between open
      abdominal aortic aneurysms repair and endovascular repair. Consideration of the
      factors identified in this study that predict reduced long-term survival for open
      abdominal aortic aneurysms repair and endovascular repair should be considered
      when deciding repair of abdominal aortic aneurysm.

PMID- 25972031
TI  - Description of a new technique for repairing chronic type B dissections that
      involve visceral branches being fed by both true and false lumen by using both
      lumens as conduits.
AB  - Here we present three cases performed using a novel technique where aortic flow
      is compartmentalized proximal to the target vessels through a physician-modified
      endograft. The visceral segment is then further compartmentalized by the use of
      another physician modified endograft. By compartmentalizing the flow proximal to
      the visceral segment, both the true lumen and false lumen can be used as conduits
      for coextensive bridging stent grafts. Overall, patients have tolerated this
      procedure extremely well, and while further study and follow-up must be
      conducted, this procedure could offer a reasonable long-term solution to
      thoracoabdominal aortic aneurysms complicated by dissection. 

PMID- 25972032
TI  - Perspectives on endovascular training in traditional 5+2 vascular surgery
      fellowship training programs.
AB  - This study aimed to compare expectations and experiences of fellows to those of
      faculty in vascular surgery fellowship programs with regard to endovascular
      training. Anonymous surveys were sent to fellows (n = 235) and program directors
      (n = 147), with 79 fellows and 65 faculty members responding. Fellows noted
      higher expectations of their endovascular skills prior to starting fellowship
      than the faculty group reported expecting. Faculty assessed fellows' pre-training
      endovascular skills at a significantly lower level than the fellows' self
      assessment. Fellows were significantly less satisfied with the structured aspects
      of endovascular training than the faculty believed them to be. Only 3% of fellows
      vs. 32% of faculty felt that the presence of an endovascular simulator affected
      how residents ranked fellowship programs during the match. In conclusion,
      incoming fellows in vascular surgery fellowship programs have high expectations
      of themselves, but may overestimate their actual pre-training endovascular
      skills. Fellows desire more structured endovascular training, which is not
      recognized by faculty. Endovascular simulators are valued, but may not be a
      significant draw in the match process. 

PMID- 25972033
TI  - The association of simple renal cysts with abdominal aortic aneurysms and their
      impact on renal function after endovascular aneurysm repair.
AB  - We validated the association of simple renal cysts with abdominal aortic aneurysm
      and other cardiovascular factors and assessed simple renal cysts' impact on renal
      function before and after endovascular abdominal aortic aneurysm repair. A
      retrospective analysis of prospectively collected data was conducted. Computed
      tomography angiograms of 100 consecutive male patients with abdominal aortic
      aneurysm who underwent endovascular abdominal aortic aneurysm repair (Group 1)
      were reviewed and compared with 100 computed tomography angiogram of aged-matched
      male patients without abdominal aortic aneurysm (Group 2). Patients' demographic
      data, risk factors, abdominal aortic aneurysm diameter, the presence of simple
      renal cyst and laboratory tests were recorded. No difference was observed between
      the two groups in respect to other cardiovascular risk factors except
      hyperlipidemia with higher prevalence in Group 1 (p < 0.05). Presence of simple
      renal cysts was independently associated with age (p < 0.05) and abdominal aortic
      aneurysm (p = 0.0157). There was no correlation between simple renal cysts and
      abdominal aortic aneurysm size or pre-operative creatinine and urea levels. No
      difference was observed in post-operative creatinine and urea levels either
      immediately after endovascular abdominal aortic aneurysm repair or in 12-month
      follow-up. In male patients, the presence of simple renal cysts is associated
      with abdominal aortic aneurysm and is increasing with age. However, their
      presence is neither associated with impaired renal function pre-endovascular
      abdominal aortic aneurysm repair and post-endovascular abdominal aortic aneurysm
      repair nor after 12-month follow-up. 

PMID- 25972034
TI  - DMD mutation spectrum analysis in 613 Chinese patients with dystrophinopathy.
AB  - Dystrophinopathy is a group of inherited diseases caused by mutations in the DMD
      gene. Within the dystrophinopathy spectrum, Duchenne and Becker muscular
      dystrophies are common X-linked recessive disorders that mainly feature striated
      muscle necrosis. We combined multiplex ligation-dependent probe amplification
      with Sanger sequencing to detect large deletions/duplications and point mutations
      in the DMD gene in 613 Chinese patients. A total of 571 (93.1%) patients were
      diagnosed, including 428 (69.8%) with large deletions/duplications and 143
      (23.3%) with point mutations. Deletion/duplication breakpoints gathered mostly in
      introns 44-55. Reading frame rules could explain 88.6% of deletion mutations. We
      identified seventy novel point mutations that had not been previously reported.
      Spectrum expansion and genotype-phenotype analysis of DMD mutations on such a
      large sample size in Han Chinese population would provide new insights into the
      pathogenic mechanism underlying dystrophinopathies. 

PMID- 25972036
TI  - Green synthesis and structural characterization of selenium nanoparticles and
      assessment of their antimicrobial property.
AB  - In the present study, selenium nanoparticles were biologically synthesized by non
      pathogenic, economic and easy to handle bacterium Ralstonia eutropha. The
      selenium oxo anion was reduced to selenium nanoparticles in the presence of the
      bacterium. The bacterium was grown aerobically in the reaction mixture. An
      extracellular, stable, uniform, spherical selenium nanoparticle was
      biosynthesized. The TEM analysis revealed that the biosynthesized selenium
      nanoparticles were spherical in shape with size range of 40-120 nm. XRD and SAED
      analysis showed that nanocrystalline selenium of pure hexagonal phase was
      synthesized. The formation of actinomorphic trigonal selenium nanorods was also
      observed. A mechanism of biosynthesis of selenium nanoparticles by R. eutropha
      was proposed. The biosynthesized selenium nanoparticles were investigated for
      their antimicrobial activity against potential pathogens. Selenium nanoparticles
      showed excellent antimicrobial activity. The 100, 100, 250 and 100 ug/ml selenium
      nanoparticles were found to inhibit 99 % growth of Pseudomonas aeruginosa,
      Staphylococcus aureus, Escherichia coli and Streptococcus pyogenes, respectively.
      Similarly, the 500 ug/ml of selenium nanoparticles was found to inhibit the
      growth of pathogenic fungi Aspergillus clavatus. The antimicrobial efficacy of
      selenium nanoparticle was comparable with commercially available antibiotic drug
      Ampicillin. 

PMID- 25972035
TI  - Association of common variants in the calcium-sensing receptor gene with serum
      calcium levels in East Asians.
AB  - Calcium is a universal intracellular messenger that has an important role in
      controlling various cellular processes. In this study, we explored genetic
      polymorphisms to identify novel loci influencing serum calcium levels in East
      Asians through a two-stage genome-wide association study with the sample of 8642
      unrelated Koreans (4558 for discovery and 4093 for replication). Using single
      nucleotide polymorphism (SNP) arrays, we discovered 963 associated SNPs in stage
      1, and replicated 105 SNPs among them in stage 2. We examined them in a combined
      set of stage 1 and 2 samples and observed that 65 SNPs were significantly
      associated with serum calcium levels. Among them, rs13068893 in the CASR gene
      showed the strongest significance (P=3.85 * 10(-8)). Considering the high allele
      frequency and significance level of the rs13068893C>G in the CASR gene, this SNP
      may have a key role in regulating the serum calcium level. We also successfully
      replicated the four loci (CASR, CSTA, DGKD and GCKR) using our data set that have
      been previously reported to be significantly associated with calcium levels in
      Europeans and Indians. Further studies with more East Asian subjects or meta
      analyses on them may enable validation of our results and identification of novel
      genetic loci associated with serum calcium levels. 

PMID- 25972037
TI  - Total, regional and unilateral body composition of professional English first
      class cricket fast bowlers.
AB  - There have been few reports of advanced body composition profiles of elite fast
      bowlers in the sport of cricket. Therefore, the aim of the current study was to
      determine total, regional and unilateral body composition characteristics of
      elite English first-class cricket fast bowlers in comparison with matched
      controls, using dual-energy X-ray absorptiometry (DXA). Twelve male fast bowlers
      and 12 age-matched, non-athletic controls received one total-body DXA scan.
      Anthropometric data were obtained as well as left and right regional (arms, legs
      and trunk) fat mass, lean mass and bone mineral content. Fast bowlers were
      significantly taller and heavier than controls (P < 0.05). Relative to body mass,
      fast bowlers possessed greater lean mass in the trunk (80.9 +/- 3.7 vs. 76.7 +/-
      5.9%; P = 0.047) and bone mineral content in the trunk (2.9 +/- 0.3 vs. 2.6 +/-
      0.3%; P = 0.049) and legs (5.4 +/- 0.5 vs. 4.6 +/- 0.6%; P = 0.003). In the arm
      region, fast bowlers demonstrated significantly greater unilateral differences in
      bone mineral content (10.6 +/- 6.6 vs. 4.5 +/- 3.9%; P = 0.012). This study
      provides specific body composition values for elite-level fast bowlers and
      highlights the potential for muscle and bone imbalances that may be useful for
      conditioning professionals. Our findings also suggest beneficial adaptations in
      body composition and bone mass in fast bowlers compared with their non-athletic
      counterparts.

PMID- 25972038
TI  - Kinetics of aggregation and growth processes of PEG-stabilised mono- and
      multivalent gold nanoparticles in highly concentrated halide solutions.
AB  - 5-6 nm gold nanoparticles were prepared by hydrolytic decomposition of
      [NMe4][Au(CF3)2] and functionalized in situ with mono- and multivalent thiolated
      PEG ligands. Time-dependent changes of the nanoparticles were monitored in
      aqueous NaCl, NaBr, and NaI solutions by UV-Vis spectroscopy, TEM, and HRTEM. The
      purely sterically protected particles are stable in <=1 M NaCl and NaBr
      solutions, regardless of the valence of the ligands. At higher concentrations
      (>=2 M), the monovalent stabilized particles show minor reaction limited
      colloidal aggregation. In NaBr but not in NaCl solutions a minor Ostwald ripening
      also occurs. The divalent stabilized particles remain colloidally stable in both
      halide solutions, even if the temperature is raised or the concentration is
      increased above 2 M. In <=1 M aqueous NaI solutions the particles remain stable.
      Above, the monovalent stabilized particles undergo an oxidative reaction,
      resulting in a time-dependent shift and broadening of the absorbance spectrum.
      Finally, this process slows down while the width of the spectra slightly narrows.
      The kinetics of this process can be described by a two-step sigmoidal process,
      comprising a slow induction period where active species are formed, followed by a
      fast growth and aggregation process. The increasing concentration of fused
      structures from the aggregates during this process results in a narrowing of the
      size distributions. The divalent stabilized particles show only some minor
      broadening and a slight shift of the absorbance spectra in <=3 M NaI solutions.
      These observations confirm the excellent stability of the multivalent stabilized
      particles from this chloride-free particle synthesis.

PMID- 25972040
TI  - Differential Effects of Intrauterine Growth Restriction on the Regional
      Neurochemical Profile of the Developing Rat Brain.
AB  - Intrauterine growth restricted (IUGR) infants are at increased risk for
      neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may
      be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and
      normally grown (NG) 7-day old rat pups using in vivo 1H magnetic resonance (MR)
      spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at
      gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from
      the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N =
      13) rats. In the cortex, IUGR resulted in lower concentrations of
      phosphocreatine, glutathione, taurine, total choline, total creatine (P < 0.01)
      and [glutamate]/[glutamine] ratio (P < 0.05). Lower taurine concentrations were
      observed in the hippocampus (P < 0.01) and striatum (P < 0.05). IUGR
      differentially affects the neurochemical profile of the P7 rat brain regions.
      Persistent neurochemical changes may lead to cortex-based long-term
      neurodevelopmental deficits in human IUGR infants.

PMID- 25972042
TI  - Sequestering uranium from UO2(CO3)3(4-) in seawater with amine ligands: density
      functional theory calculations.
AB  - The polystyrene-supported primary amine -CH2NH2 has shown an at least 3-fold
      increase in uranyl capacity compared to a diamidoxime ligand on a polystyrene
      support. This study aims to understand the coordination of substitution complexes
      from UO2(CO3)3(4-) and amines using density functional theory calculations. Four
      kinds of amines (diethylamine (DEA), ethylenediamine (EDA), diethylenetriamine
      (DETA) and triethylenetetramine (TETA)) were selected because they belong to
      different classes and have different chain lengths. The geometrical structures,
      electronic structures and the thermodynamic stabilities of various substitution
      complexes, as well as the trends in their calculated properties were investigated
      at equilibrium. In these optimized complexes, DEA groups bind to uranyl as
      monodentate ligands; EDA groups serve as monodentate and bidentate ligands; DETA
      groups act as monodentate and tridentate ligands; while TETA groups serve as
      monodentate, bidentate and tridentate ligands. The thermodynamic analysis
      confirmed that the primary amines coordinate to uranyl more strongly than does
      the secondary amine. The stabilities of substitution complexes with primary
      amines were calculated to decrease with increasing chain length of the amine,
      except for UO2(L2)(2+). Of the complexes analyzed, only UO2L(CO3)2(2-) (L = EDA
      and DETA) and UO2L2CO3 (L = EDA) were predicted to form from the substitution
      reactions with UO2(CO3)3(4-) and protonated amines as reactants in aqueous
      solution. Amines were calculated to be comparable to, or sometimes weaker than,
      amidoximate in replacing CO3(2-) in UO2(CO3)3(4-) to coordinate to uranium.
      Therefore, the coordination mechanism, in which amines replace carbonates to bind
      to uranyl, is not primarily responsible for the experimentally observed 3-fold or
      greater increase in uranyl capacity of primary amines compared to a diamidoxime
      ligand. Based on the results of our calculations, we believe that the cation
      exchange mechanism, in which the protonated amines bind to uranyl tricarbonate
      directly, plays a leading role in the uranium recovery from seawater by amines. 

PMID- 25972041
TI  - Modeling-based determination of physiological parameters of systemic VOCs by
      breath gas analysis: a pilot study.
AB  - In this paper we develop a simple two compartment model which extends the Farhi
      equation to the case when the inhaled concentration of a volatile organic
      compound (VOC) is not zero. The model connects the exhaled breath concentration
      of systemic VOCs with physiological parameters such as endogenous production
      rates and metabolic rates. Its validity is tested with data obtained for isoprene
      and inhaled deuterated isoprene-D5.

PMID- 25972044
TI  - Copper(I)-photocatalyzed trifluoromethylation of alkenes.
AB  - Using the photoreducible Cu(II) precatalyst 2, trifluoromethylation reactions of
      alkenes are conducted effectively at low copper loading (0.1-0.5 mol%) on
      exposing the reaction mixture to sunlight/ambient light. 

PMID- 25972043
TI  - Opportunistic mammography screening provides effective detection rates in a
      limited resource healthcare system.
AB  - BACKGROUND: Breast cancer is the leading cause of cancer deaths in women world
      wide. In low and middle income countries, where there are no population-based
      mammographic screening programmes, late presentation is common, and because of
      inadequate access to optimal treatment, survival rates are poor. Mammographic
      screening is well-studied in high-income countries in western populations, and
      because it has been shown to reduce breast cancer mortality, it has become part
      of the healthcare systems in such countries. However the performance of
      mammographic screening in a developing country is largely unknown. This study
      aims to evaluate the performance of mammographic screening in Malaysia, a middle
      income country, and to compare the stage and surgical treatment of screen
      detected and symptomatic breast cancer. METHODS: A retrospective review of 2510
      mammograms performed from Jan to Dec 2010 in a tertiary medical centre is carried
      out. The three groups identified are the routine (opportunistic) screening group,
      the targeted (high risk) screening group and the diagnostic group. The
      performance indicators of each group is calculated, and stage at presentation and
      treatment between the screening and diagnostic group is analyzed. RESULTS: The
      cancer detection rate in the opportunistic screening group, targeted screening
      group, and the symptomatic group is 0.5 %, 1.25 % and 26 % respectively. The
      proportion of ductal carcinoma in situ is 23.1 % in the two screening groups
      compared to only 2.5 % in the diagnostic group. Among the opportunistic screening
      group, the cancer detection rate was 0.2 % in women below 50 years old compared
      to 0.65 % in women 50 years and above. The performance indicators are within
      international standards. Early-staged breast cancer (Stage 0-2) were 84.6 % in
      the screening groups compared to 61.1 % in the diagnostic group. CONCLUSION: From
      the results, in a setting with resource constraints, targeted screening of high
      risk individuals will give a higher yield, and if more resources are available,
      population-based screening of women 50 and above is effective. Opportunistic
      mammographic screening is feasible and effective in a middle income country with
      performance indicators within international standards. Waiting until women are
      symptomatic will lead to more advanced cancers.

PMID- 25972039
TI  - GLAST But Not Least--Distribution, Function, Genetics and Epigenetics of L
      Glutamate Transport in Brain--Focus on GLAST/EAAT1.
AB  - Synaptically released L-glutamate, the most important excitatory neurotransmitter
      in the CNS, is removed from extracellular space by fast and efficient transport
      mediated by several transporters; the most abundant ones are EAAT1/GLAST and
      EAAT2/GLT1. The review first summarizes their location, functions and basic
      characteristics. We then look at genetics and epigenetics of EAAT1/GLAST and
      EAAT2/GLT1 and perform in silico analyses of their promoter regions. There is one
      CpG island in SLC1A2 (EAAT2/GLT1) gene and none in SLC1A3 (EAAT1/GLAST)
      suggesting that DNA methylation is not the most important epigenetic mechanism
      regulating EAAT1/GLAST levels in brain. There are targets for specific miRNA in
      SLC1A2 (EAAT2/GLT1) gene. We also note that while defects in EAAT2/GLT1 have been
      associated with various pathological states including chronic neurodegenerative
      diseases, very little is known on possible contributions of defective or
      dysfunctional EAAT1/GLAST to any specific brain disease. Finally, we review
      evidence of EAAT1/GLAST involvement in mechanisms of brain response to alcoholism
      and present some preliminary data showing that ethanol, at concentrations which
      may be reached following heavy drinking, can have an effect on the distribution
      of EAAT1/GLAST in cultured astrocytes; the effect is blocked by baclofen, a GABA
      B receptor agonist and a drug potentially useful in the treatment of alcoholism.
      We argue that more research effort should be focused on EAAT1/GLAST, particularly
      in relation to alcoholism and drug addiction. 

PMID- 25972045
TI  - Growth in sales of custom-compounded menopause hormones.

PMID- 25972046
TI  - Treating trade: the case for clinical engagement with regional trade agreements.

PMID- 25972047
TI  - H, C, and O Stable Isotope Ratios of Passito Wine.
AB  - In this study we investigated the effect of the grape withering process occurring
      during the production of Italian passito wines on the variability of the (D/H)I,
      (D/H)II, delta(13)C, and delta(18)O of wine ethanol and the delta(18)O of wine
      water. The production of PDO Erbaluce di Caluso Passito in five different cellars
      in Piedmont (Italy) was considered in two successive years. Moreover, samples of
      17 different traditional Italian passito wines taken at different stages of
      maturation were taken into account. We found that the delta(18)O of must and wine
      water and the delta(18)O of ethanol decrease in the case of passito wines
      produced in northern and central Italy using postharvest drying of the grapes in
      dedicated ventilated or unventilated fruit drying rooms (fruttaio), during autumn
      winter. For passito wines produced in southern Italy, where the main technique
      involves withering on the plant (en plein air), delta(18)O tends to increase. The
      (DH)I of wine ethanol did not change during withering, whereas the (DH)II and
      delta(13)C values changed slightly, but without any clear trend. Particular
      attention must be therefore paid in the evaluation of the delta(18)O data of
      passito wines for fraud detection. 

PMID- 25972048
TI  - Changes in quality of life, healthcare use, and substance use in HIV/hepatitis C
      coinfected patients after hepatitis C therapy: a prospective cohort study.
AB  - OBJECTIVE: Clinical benefits of achieving a sustained virologic response (SVR)
      with hepatitis c virus (HCV) therapy beyond reducing liver-related outcomes have
      not been documented in HIV-coinfected patients, who have multiple competing
      health problems. To gauge the potential benefits of curing HCV in coinfected
      people, we examined changes in health-related quality of life (HRQOL), healthcare
      and substance use, and overall mortality after treatment for HCV Coinfection.
      DESIGN: Prospective multicentre cohort study. METHODS: Among patients treated for
      HCV in the Canadian Coinfection Cohort study, self-reported HRQOL (using the EQ
      5D), inpatient and outpatient medical visits, and substance use were assessed
      before, 6 months and 1 year after completing HCV therapy, comparing SVR-achievers
      and non-responders. Analysis of covariance and zero-inflated negative binomial
      regression were used to model the effects of SVR on HRQOL and healthcare use,
      respectively. RESULTS: Of 1145 patients chronically infected with HCV, 223 (19%)
      received treatment while under follow-up in the cohort and had HRQOL data
      collected - 86 (36%) achieved SVR, 68 (29%) did not, 30 (13%) had ongoing
      treatment, and 39 (17%) had unknown responses. Compared to non-responders, those
      achieving a SVR had higher HRQOL scores over time (11-unit increase 1 year
      posttreatment, 95% CI: 2, 21 measured 1 year posttreatment) and a lower rate of
      health service utilization (adjusted incidence rate ratio: 0.5, 95% CI: 0.3,
      0.9). Short-term mortality was low but appeared lower in SVR-achievers (incidence
      rates: 0.10 vs 0.12 deaths per 100 person-years). However, after successful
      treatment, a substantial number of patients increased alcohol consumption and
      continued to inject drugs. CONCLUSIONS: Successful HCV treatment results in a
      range of health benefits for HIV/HCV-coinfected patients. Ongoing substance use,
      however, may mitigate the short- and long-term benefits associated with curing
      HCV.

PMID- 25972049
TI  - Leiomyosarcoma of Larynx as a Metachronous Tumor of Squamous Cell Carcinoma: An
      Unusual Case.
AB  - Leiomyosarcomas (LMSs) are malignant tumors of smooth muscles accounting for 5-6%
      of all soft tissue sarcomas. They are mostly seen in the gastrointestinal
      tractus, the uterus, and the retroperitoneum. Soft tissue sarcomas comprise <1%
      of all laryngeal malignancies, most of which are chondrosarcomas. Laryngeal LMSs
      are rarely seen malignancies, which are published as case reports. We presented a
      case of laryngeal LMS, which was seen 4 years later in a laryngeal squamous cell
      carcinoma patient who underwent laryngeal laser microsurgery. We discussed the
      diagnosis and treatment algorithm in the light of the present literature. 

PMID- 25972050
TI  - Photodynamic activity of nanostructured fabrics grafted with xanthene and
      thiazine dyes against opportunistic fungi.
AB  - Fungi are an important class of human pathogens for which considerable research
      has gone into defeating them. The photodynamic effects of rose bengal (RB),
      phloxine B (PB), azure A (AA), and toluidine blue O (TBO) dyes to inhibit
      Aspergillus fumigatus, Aspergillus niger, Trichoderma viride, Penicillium
      funiculosum, and Chaetomium globosum were investigated grafted to nano- and micro
      structured fabrics. Three antifungal tests conducted: broth microdilution test of
      free dyes, zone of inhibition and quantitative antifungal assays on fabrics
      grafted with dyes. In the broth microdilution test, free RB displayed the lowest
      MIC at 32 MUM to inhibit visible hyphal growth and germination but the antifungal
      ability of MIC for other photosensitizers below 63 MUM was insignificant. RB and
      PB showed lower MIC than AA and TBO. In the inhibition zone tests, nanostructured
      fabrics grafted with RB and PB did not display fungal growth on the surface. Most
      microstructured fabrics grafted with AA and TBO showed little inhibition. In
      quantitative antifungal assay, nanostructured fabrics grafted with RB has the
      largest inhibition rate on T. viride and the lowest inhibition rate on P.
      funiculosum and the results showed the increasing inhibition rate in the order of
      AA < TBO < PB < RB.

PMID- 25972051
TI  - Suppurative cervical lymphadenitis in infancy: microbiology and sociology.
AB  - OBJECTIVE: To investigate the associations between patient age, sociological
      factors, and the microbiology of pediatric neck infections. METHODS:
      Retrospective chart review of children up to 5 years old who underwent surgical
      management of suppurative cervical lymphadenitis. RESULTS: A total of 76
      individuals met inclusion criteria; 93% of culture-positive infections were
      caused by Staphylococcus aureus in infants, compared with 59% in children between
      13 months and 5 years of age (P = .002). Of the S aureus isolates, 51% were
      methicillin-resistant S aureus (MRSA) and 49% were methicillin-sensitive S
      aureus. Methicillin resistance was associated with African American race (P =
      .004); 67% of participants received empirical antibiotics prior to admission. Of
      these, 73% received antibiotics in the beta-lactam class, and 25% received
      treatment with clindamycin. CONCLUSIONS: Incidence of MRSA is high in infants
      with cervical lymphadenitis who fail empirical antibiotic therapy and require
      surgical management. Empirical coverage for cervical lymphadenitis with beta
      lactam antibiotics may provide inadequate coverage for early infection in this
      population.

PMID- 25972052
TI  - Reduced walking speed and distance as harbingers of the approaching grim reaper.
AB  - Although treadmill exercise testing can provide an assessment of
      cardiorespiratory fitness, which serves as an independent prognostic indicator,
      numerous studies now suggest that usual gait speed, time, or distance covered
      during walk performance tests and weekly walking distance/time are powerful
      predictors of mortality and future cardiovascular events in selected patients.
      This review summarizes the relation between these variables and their association
      with cardiovascular and all-cause mortality, with specific reference to potential
      underlying mechanisms and implications for the clinician. Contemporary health
      care providers have escalating opportunities to promote lifestyle physical
      activity using pedometers, accelerometers, and smartphone-based health and
      wellness applications. In conclusion, fitness and/or ambulatory indexes should be
      considered a "vital sign" in middle-aged and older adults. 

PMID- 25972053
TI  - Prevalence and prediction of obstructive coronary artery disease in patients
      referred for valvular heart surgery.
AB  - Current guidelines recommend a coronary evaluation before valvular heart surgery
      (VHS). Diagnostic coronary angiography is recommended in patients with known
      coronary artery disease (CAD) and those with high pretest probability of CAD. In
      patients with low or intermediate pretest probability of CAD, the guidelines
      recommend coronary computed tomographic angiography. However, there are no tools
      available to objectively assess a patient's risk for obstructive CAD before VHS.
      To address this deficit, 5,360 patients without histories of CAD who underwent
      diagnostic coronary angiography as part of preoperative evaluation for VHS were
      identified. Obstructive CAD was defined as >=50% stenosis in >=1 artery. Of the
      patients assessed, 1,035 (19.3%) were found to have obstructive CAD. Through
      multivariate analysis, age, gender, diabetes, renal dysfunction, hyperlipidemia,
      and a family history of premature CAD were found to be associated with the
      presence of obstructive CAD (p <0.001 for all). After adjustment, the specific
      dysfunctional valve was not associated with the presence of obstructive CAD.
      Patients were then randomly split into derivation and validation cohorts. Within
      the derivation cohort, using only age, gender, and the presence or absence of
      risk factors, a model was constructed to predict the risk for obstructive CAD (C
      statistic 0.766, 95% confidence interval 0.750 to 0.783). The risk prediction
      model performed well within the validation cohort (C statistic 0.767, 95%
      confidence interval 0.751 to 0.784, optimism 0.004). The bias-corrected C
      statistic for the model was 0.765 (95% confidence interval 0.748 to 0.782). In
      conclusion, this novel risk prediction tool can be used to objectively risk
      stratify patients who undergo preoperative evaluation before VHS and to
      facilitate appropriate triage to computed tomographic angiography or diagnostic
      coronary angiography. 

PMID- 25972054
TI  - Effect of early direct current cardioversion on the recurrence of atrial
      fibrillation in patients with persistent atrial fibrillation.
AB  - In patients with persistent atrial fibrillation (AF), the sinus rhythm (SR) can
      be restored by direct current cardioversion (DCC), although the recurrence of AF
      after successful DCC is common. We examined whether transesophageal
      echocardiography (TEE)-guided early DCC, compared with the conventional approach
      of DCC after 3 weeks of anticoagulation with dabigatran-etexilat, reduces the
      recurrence of AF. A total of 126 consecutive patients with persistent AF were
      randomly assigned to a TEE followed by early DCC (n = 65) or to a conventional
      treatment with dabigatran-etexilat for 3 weeks followed by DCC (n = 61). None of
      the patients received any antiarrhythmic treatment other than beta blockers, and
      all the DCCs were successful. Forty-eight-hour Holter monitoring was performed at
      28 days and at 3, 6, and 12 months after the DCC. The primary outcome was AF
      recurrence lasting >=30 seconds. The analysis was stratified by AF duration <60
      (n = 62) or >60 days (n = 64) before DCC. We observed a significant reduction in
      the AF recurrence risk (p = 0.003) in patients with persistent AF <60 days who
      received early DCC, but there was no significant benefit of early DCC (p = 0.456)
      in patients with persistent AF lasting >60 days. The recurrence-free survival
      probability at 28 days in patients with persistent AF <60 days was 0.27 (95%
      confidence interval 0.14 to 0.51) in the conventional treatment group compared
      with 0.69 (95% confidence interval 0.54 to 0.87; p = 0.006) in the early DCC
      group. A benefit of early DCC persisted throughout 12 months of follow-up. In
      conclusion, TEE-guided early DCC in patients with persistent AF <60 days results
      in a significant reduction of AF recurrence.

PMID- 25972055
TI  - Associations between the five-factor model of personality and leukocyte telomere
      length in elderly men and women: The Helsinki Birth Cohort Study (HBCS).
AB  - OBJECTIVE: Personality traits have been associated with cardiometabolic diseases
      and mental disorders as well as with longevity. However, the underlying
      mechanisms are not fully understood. Accelerated cellular aging may play a role
      in this process. We studied whether personality traits in late adulthood, as
      defined in the five-factor model (FFM), were associated with a biomarker of
      cellular vitality, leukocyte telomere length (LTL). METHODS: At a mean age of
      63.4 (SD=2.8) years, 1671 (742 men, 929 women) participants from the Helsinki
      Birth Cohort Study filled in the Neuroticism, Extraversion and Openness
      Personality Inventory (NEO-PI). LTL was measured at a mean age of 61.5 (SD=2.9)
      years by using a real-time quantitative PCR method. RESULTS: None of the FFM
      personality dimensions were significantly associated with the LTL in the analyses
      of both sexes combined. We however found interaction between sex and
      agreeableness (B=0.020, 95% CI=.008, 0.032, p=.001) and in the sex-specific
      analyses, men who scored higher on agreeableness (B=-0.086, 95% CI=-0.155, 
      0.016, p=.016) and women who scored lower on agreeableness (B=0.074, 95%
      CI=0.014, 0.134, p=.016) had shorter LTL. CONCLUSIONS: FFM dimensions of
      personality were not associated with LTL in a sample of elderly individuals. The
      counterintuitive and sporadic sex specific finding on agreeableness requires
      replication. Overall our findings suggest that LTL, a biomarker of cellular
      aging, may not offer insight into the associations between personality, longevity
      and health.

PMID- 25972056
TI  - Prevention of posttraumatic stress disorder with propranolol: A meta-analytic
      review.
AB  - OBJECTIVE: PTSD is associated with significant morbidity and its prevention could
      reduce a significant burden of individual and societal suffering. The aim of this
      study is to conduct a systematic review of the literature on the prevention of
      PTSD by using propranolol following exposure to a traumatic event. METHODS:
      Authors searched all studies published in the MEDLINE database up to November
      2014 and reviewed textbooks and reference lists. Authors of relevant articles
      were contacted. Clinical trials and observational studies were included if they
      investigated the effect of propranolol in the acute post-trauma phase to prevent
      PTSD symptoms for subjects 18 years of age or older. PTSD was diagnosed according
      to DSM or widely accepted and validated diagnostic tools. A random-effects model
      was used to perform meta-analysis. RESULTS: Five studies were included in the
      review for meta-analysis. Heterogeneity was not significant (tau2=0.0, S.E=0.247;
      Cochran's Q(4)=1.870, p=0.760; I2=0%). Relative risk point estimate to the effect
      of propranolol to prevent PTSD was 0.92 (95% CI: 0.55-1.55). Asymmetry was not
      significant under the Egger test (z=-1.34; p=0.180). CONCLUSIONS: The findings
      suggest that propranolol treatment after the traumatic event did not alter the
      incidence of PTSD, although physiological responses are generally attenuated. The
      studies included small sample sizes, which can preclude the detection of
      significant results. Authors believe future studies should achieve larger sample
      sizes and longer follow-up periods.

PMID- 25972057
TI  - [Undesired treatment effects in behavior group therapy: Frequency and spectrum].
AB  - BACKGROUND: Psychotherapy not only has positive but also negative effects, which
      is especially true for group psychotherapy due to psychodynamic and interactional
      processes. METHODS: Using the UE-G questionnaire 71 patients who participated in
      cognitive behavioral group psychotherapy reported on negative experiences in the
      context of the group therapy. The answers were then validated in a qualitative
      interview. RESULTS: Of the patients 98.6% reported about at least one negative
      experience and 43.7% about severe or extremely severe negative experiences. Most
      prominent was the induction of hopelessness and demoralization by what patients
      saw and heard from other patients in the group. CONCLUSION: Burdensome and
      therefore undesired treatment effects are regularly seen in group psychotherapy,
      because of treatment or patient related factors. In any case they must be taken
      into account during treatment, in the training of group psychotherapists and in
      quality control.

PMID- 25972058
TI  - Posttraumatic spinal cord herniation.

PMID- 25972059
TI  - Perfusion imaging insights into SMART syndrome: a case report.

PMID- 25972060
TI  - Neurogenic sphincters dysfunction as unusual clinical picture of ADEM.

PMID- 25972061
TI  - Factors affecting bone mineral density in postmenopausal women.
AB  - This study aimed to determine the relationship between bone mineral density (BMD)
      and demographic, biochemical, and clinical features according to BMD measurement
      sites. The results indicated that BMD correlates negatively with menopause
      duration, parity, and history of fractures but positively correlates with
      obesity, physical activity, education, and serum ferritin. PURPOSE/INTRODUCTION:
      Osteoporosis (OP) is an important cause of morbidity and mortality in the elderly
      people. The impacts of various factors on bone mineral density (BMD) differ
      across diverse population. We hypothesized that the influences of factors which
      affect BMD vary according to BMD measurement sites. The aim of this study was to
      determine the relationship between BMD in the femoral neck (FN) and lumbar spine
      (LS) with some common clinical, demographic, and biochemical parameters in
      postmenopausal women. METHODS: In this cross-sectional case-control study, all
      postmenopausal women of the Amirkola Health and Ageing Project (AHAP) who
      performed bone densitometry were included. BMD at FN and LS was measured by DXA
      method. Data regarding clinical, demographic, and biochemical characteristics
      were provided. OP was diagnosed by the International Society for Clinical
      Densitometry criteria. Pearson correlation and multivariate regression analyses
      with simultaneous adjustment were performed to determine relationship. RESULTS:
      Five hundred thirty-seven women with mean age of 67.9 +/- 6.7 years and mean
      menopause duration (MD) of 15.8 +/- 5.1 years were studied. MD correlated
      negatively with FN-BMD and LS-BMD g/cm(2) (r = -0.405, p = 0.001 and r = -0.217,
      p = 0.001). Body mass index (BMI) correlated positively with FN and LS-BMD
      g/cm(2) (r = 0.397, p = 0.001 and r = 0.311, p = 0.001). The association of MD
      with risk of FN-OP was stronger than LS-OP. Obesity and metabolic syndrome (MS)
      and higher serum ferritin reduced the risk of OP at both LS and FN similarly,
      whereas the impacts of parity, prior fracture, high level of education, and
      physical activity were significantly different across BMD measurement sites.
      CONCLUSION: The results of this study indicated a significant association between
      OP and MD, obesity, parity, MS, history of fracture, serum ferritin, level of
      education, and physical activity. However, the direction and the strength of
      association varied across BMD measurement sites.

PMID- 25972062
TI  - A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World
      Impact on Survival, Quality of Life and Costs.
AB  - PURPOSE: The purpose of this study was to assess the overall burden of pancreatic
      cancer in Europe, with a focus on survival time in a real-world setting, and the
      overall healthy life lost to the disease. METHODS: Real-world data were retrieved
      from peer-reviewed, observational studies identified by an electronic search. We
      performed two de novo analyses: a proportional shortfall analysis to quantify the
      proportion of healthy life lost to pancreatic cancer and an estimation of the
      aggregate life-years lost annually in Europe. RESULTS: Ninety-one studies were
      included. The median, age-standardised incidence of pancreatic cancer per 100,000
      was 7.6 in men and 4.9 in women. Overall median survival from diagnosis was 4.6
      months; median survival was 2.8-5.7 months in patients with metastatic disease.
      The proportional shortfall analysis showed that pancreatic cancer results in a 98
      % loss of healthy life, with a life expectancy at diagnosis of 4.6 months
      compared to 15.1 years for an age-matched healthy population. Annually, 610,000
      915,000 quality-adjusted life-years (QALYs) are lost to pancreatic cancer in
      Europe. Patients had significantly lower scores on validated health-related
      quality of life instruments versus population norms. CONCLUSIONS: To the best of
      our knowledge, this is the first study to systematically review real-world
      overall survival and patient outcomes of pancreatic cancer patients in Europe
      outside the context of clinical trials. Our findings confirm the poor prognosis
      and short survival reported by national studies. Pancreatic cancer is a
      substantial burden in Europe, with nearly a million aggregate life-years lost
      annually and almost complete loss of healthy life in affected individuals.

PMID- 25972063
TI  - Long-Term Survival of Patient with Epstein-Barr Virus-Positive Gastric Cancer
      Treated with Chemotherapy: Case Report.

PMID- 25972064
TI  - Anorectal Melanoma with Bilateral Ovarian Metastases.

PMID- 25972065
TI  - A Fulminant Case of Leptomeningeal Carcinomatosis Secondary to Esophageal
      Adenocarcinoma.

PMID- 25972066
TI  - The use of adalimumab, etanercept, golimumab and infliximab in rheumatic
      pathologies: variation between label dosage and real-world use.
AB  - Rheumatoid arthritis (AR), psoriatic arthritis (PSA) and ankylosing spondylitis
      (AS) are autoimmune systemic diseases characterized by inflammation, pain and
      joint degeneration. The objective of this study is to evaluate, under the actual
      conditions of use, dosing patterns of adalimumab, etanercept, golimumab and
      infliximab in these pathologies, and compare them with the label regimens
      recommended, as well as evaluating the financial implications of these regimen
      modifications. The study population included all adult patients diagnosed with
      RA, PSA or AS who had been treated with adalimumab, etanercept, golimumab and
      infliximab for at least 6 months between 1 January 2011 and 31 December 2013. The
      main variable of this study was to assess the dose dispensed for drugs
      administered subcutaneously and the dose prepared/administered for drugs
      administered intravenously, and the annual costs of the treatment. A total of
      5,428 episodes were included. The mean weekly dose was lower than the standard
      dose in the three pathologies studied in the patients treated with adalimumab and
      etanercept (84.3% vs 81.2% for RA, 85.0% vs 78.0% for PSA and 87.8% vs 81.6% for
      AS). The drugs with highest dose optimization in RA are etanercept (46.3%)
      followed by adalimumab (46%); however, the highest percentage of patients with
      major dose optimization corresponds to etanercept (11.6%). Both in the PA and the
      AS group, we also observed that etanercept is the drug more optimized,
      corresponding to 53.9 and 43% of patients, respectively. By contrast, 48.5% of
      patients with RA treated with infliximab required dose intensification; however,
      infliximab dose intensification in PSA and AS is not so pronounced. The practice
      of optimization of dose regimens in patients with rheumatic diseases under
      treatment with anti-TNFalpha is spreading among professionals, resulting in
      annual cost reduction in the treatment of rheumatic arthropathies. However, long
      term follow-up will be necessary to assess the influence of this optimization on
      health outcomes. 

PMID- 25972068
TI  - TEMPO-Attached Pre-fluorescent Probes Based on Pyridinium Fluorophores.
AB  - The photophysical behavior of three pyridinium-derived fluorophores, the N-aryl
      2,4,6-triphenylpyridinium, the N-aryl-5,6-dihydro-2,4-diphenylbenzo[h]quinolinium
      and the N-aryl-5,6,8,9-tetrahydro-7-phenyldibenzo[c,h]acridinium perchlorates,
      was investigated. Comparison of their fluorescence quantum yields led to the
      preparation of a novel, more sensitive pyridinium-based, TEMPO-attached
      prefluorescent probe for H-abstraction processes, the N-{4-[4-(N-oxyl-2,2,6,6
      tetramethylpiperidinyl)carbonylamino]phenyl}-5,6,8,9-tetrahydro-7
      phenyldibenzo[c,h]-acridinium perchlorate. 

PMID- 25972067
TI  - The functional anatomy of central auditory processing.

PMID- 25972069
TI  - Rh(III)-Catalyzed C-H Alkylation of Arenes Using Alkylboron Reagents.
AB  - Rhodium(III)-catalyzed direct alkylation of arenes using commercially available
      alkyltrifluoroborates is disclosed. Oximes, heteroarenes, azomethines, N
      nitrosoamines, and amides are viable directing groups to entail this
      transformation. The alkyl group in the boron reagent can be extended to primary
      alkyls, benzyl, and cycloalkyls, and the reaction proceeded with controllable
      mono- and dialkylation selectivity when both ortho C-H sites are accessible. 

PMID- 25972070
TI  - STAT1-Induced HLA Class I Upregulation Enhances Immunogenicity and Clinical
      Response to Anti-EGFR mAb Cetuximab Therapy in HNC Patients.
AB  - The goal of this study was to characterize the molecular mechanisms underlying
      cetuximab-mediated upregulation of HLA class I antigen-processing machinery
      components in head and neck cancer (HNC) cells and to determine the clinical
      significance of these changes in cetuximab-treated HNC patients. Flow cytometry,
      signaling studies, and chromatin immunoprecipitation (ChIP) assays were performed
      using HNC cells treated with cetuximab alone or with Fcgamma receptor (FcgammaR)
      bearing lymphocytes to establish the mechanism of EGFR-dependent regulation of
      HLA APM expression. A prospective phase II clinical trial of neoadjuvant
      cetuximab was used to correlate HLA class I expression with clinical response in
      HNC patients. EGFR blockade triggered STAT1 activation and HLA upregulation, in a
      src homology-containing protein (SHP)-2-dependent fashion, more prominently in
      HLA-B/C than in HLA-A alleles. EGFR signaling blockade also enhanced IFNgamma
      receptor 1 (IFNAR) expression, augmenting induction of HLA class I and TAP1/2
      expression by IFNgamma, which was abrogated in STAT1(-/-) cells. Cetuximab
      enhanced HNC cell recognition by EGFR853-861-specific CTLs, and notably enhanced
      surface presentation of a non-EGFR peptide (MAGE-3271-279). HLA class I
      upregulation was significantly associated with clinical response in cetuximab
      treated HNC patients. EGFR induces HLA downregulation through SHP-2/STAT1
      suppression. Reversal of HLA class I downregulation was more prominent in
      clinical responders to cetuximab therapy, supporting an important role for
      adaptive immunity in cetuximab antitumor activity. Abrogating EGFR-induced immune
      escape mechanisms and restoring STAT1 signaling to reverse HLA downregulation
      using cetuximab should be combined with strategies to enhance adaptive cellular
      immunity.

PMID- 25972071
TI  - Variations in the Role of Social Support on Disclosure Among Newly Diagnosed HIV
      Infected People Who Inject Drugs in Vietnam.
AB  - Stigma and perceived social support can influence the decision to disclose HIV
      positive status, especially for people who inject drugs (PWID). In this analysis,
      the association between social support and HIV disclosure among 336 newly
      diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after
      diagnosis, 34.8 % of participants had not disclosed to anyone. Disclosure to
      anyone and to a family member specifically, was associated with baseline social
      support in the form of positive interactions and a history of incarceration.
      Disclosing to a family member was less likely among those who had unprotected sex
      in the previous 3 months. Disclosure to an injecting partner was more likely
      among those with a history of being in a drug treatment program, knowing someone
      on ART and believing that ART is safe. These data suggest that social support may
      facilitate disclosure among family members, including spouses, while disclosure
      to injecting partners is greater when PWID know that ART is a safe and viable
      option.

PMID- 25972073
TI  - Is Location of Sex Associated with Sexual Risk Behaviour in Men Who Have Sex with
      Men? Systematic Review of Within-Subjects Studies.
AB  - To understand associations between location of sex and sexual risk, it is most
      helpful to compare sexual encounters within persons. We systematically reviewed
      within-subjects comparisons of sexual encounters reported by men who have sex
      with men (MSM) with respect to location of sex. Within-subjects comparisons of
      sexual risk and location of sex were eligible if they collected data post-1996
      from samples of MSM. We independently screened results and full-text records in
      duplicate. Of 6,336 deduplicated records, we assessed 138 full-text studies and
      included six, most of which compared unprotected anal intercourse against other
      anal intercourse. This small, but high quality, body of evidence suggests that
      associations between attendance at sex-on-premises venues and person-level sexual
      risk may be due to overall propensity towards unprotected sex. However, there may
      be some location factors that promote or are associated with serononconcordant
      unprotected anal intercourse. Health promoters may wish to focus on person-level
      characteristics.

PMID- 25972072
TI  - Erratum to: Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV
      Infected and Uninfected Patients: A Longitudinal Analysis of United States
      Veterans from 1997 to 2011.

PMID- 25972074
TI  - The Effect of Virtual Reality Distraction on Pain Relief During Dressing Changes
      in Children with Chronic Wounds on Lower Limbs.
AB  - It has been demonstrated that patients with chronic wounds experience the most
      pain during dressing changes. Currently, researchers focus mostly on analgesics
      and appropriate dressing materials to relieve pain during dressing changes of
      chronic wounds. However, the effect of nonpharmacologic interventions, such as
      virtual reality distraction, on pain management during dressing changes of
      pediatric chronic wounds remains poorly understood. To investigate the effect of
      virtual reality distraction on alleviating pain during dressing changes in
      children with chronic wounds on their lower limbs. A prospective randomized
      study. A pediatric center in a tertiary hospital. Sixty-five children, aged from
      4 to 16 years, with chronic wounds on their lower limbs. Pain and anxiety scores
      during dressing changes were recorded by using the Wong-Baker Faces picture
      scale, visual analogue scale, and pain behavior scale, as well as physiological
      measurements including pulse rate and oxygen saturation. Time length of dressing
      change was recorded. Virtual reality distraction significantly relieved pain and
      anxiety scores during dressing changes and reduced the time length for dressing
      changes as compared to standard distraction methods. The use of virtual reality
      as a distraction tool in a pediatric ward offered superior pain reduction to
      children as compared to standard distractions. This device can potentially
      improve clinical efficiency by reducing length time for dressing changes. 

PMID- 25972075
TI  - Do different anesthesia regimes affect hippocampal apoptosis and neurologic
      deficits in a rodent cardiac arrest model?
AB  - BACKGROUND: Different anesthesia regimes are commonly used in experimental models
      of cardiac arrest, but the effects of various anesthetics on clinical outcome
      parameters are unknown. We conducted a study in which we subjected rats to
      cardiac arrest under medetomidine/ketamine or sevoflurane/fentanyl anesthesia.
      METHODS: Asystolic cardiac arrest for 8 minutes was induced in 73 rats with a
      mixture of potassium chloride and esmolol. Daily behavioral and neurological
      examination included the open field test (OFT), the tape removal test (TRT) and a
      neurodeficit score (NDS). Animals were randomized for sacrifice on day 2 or day 5
      and brains were harvested for histology in the hippocampus cornus ammonis segment
      CA1. The inflammatory markers IL-6, TNF-alpha, MCP-1 and MIP-1alpha were assessed
      in cerebrospinal fluid (CSF). Proportions of survival were tested with the
      Fisher's exact test, repeated measurements were assessed with the Friedman's
      test; the baseline values were tested using Mann-Whitney U test and the
      difference of results of repeated measures were compared. RESULTS: In 31 animals
      that survived beyond 24 hours neither OFT, TRT nor NDS differed between the
      groups; histology was similar on day 2. On day 5, significantly more apoptosis in
      the CA1 segment of the hippocampus was found in the sevoflurane/fentanyl group.
      MCP-1 was higher on day 5 in the sevoflurane/fentanyl group (p = 0.04). All other
      cyto- and chemokines were below detection threshold. CONCLUSION: In our cardiac
      arrest model neurological function was not influenced by different anesthetic
      regimes; in contrast, anesthesia with sevoflurane/fentanyl results in increased
      CSF inflammation and histologic damage at day 5 post cardiac arrest.

PMID- 25972076
TI  - Placenta expresses anti-Mullerian hormone and its receptor: Sex-related
      difference in fetal membranes.
AB  - INTRODUCTION: Anti-Mullerian hormone (AMH) is a member of the transforming growth
      factor-beta superfamily, playing a role in sexual differentiation and
      recruitment. Since a correlation exists between AMH serum levels in cord blood
      and fetal sex, the present study aimed to identify mRNA and protein expression of
      AMH and AMHRII in placenta and fetal membranes according to fetal sex. METHODS:
      Placenta and fetal membranes samples (n = 40) were collected from women with
      singleton uncomplicated pregnancies at term. Identification of AMH protein in
      placenta and fetal membranes was carried out by immunohistochemistry and AMH and
      AMHRII protein localization by immunofluorescence, while mRNA expression was
      assessed by quantitative real-time PCR. RESULT: AMH and AMHRII mRNAs were
      expressed by placenta and fetal membranes at term, without any significant
      difference between males and females. Placental immunostaining showed a syncytial
      localization of AMH without sex-related differences; while fetal membranes
      immunostaining was significantly more intense in male than in female fetuses (p <
      0,01). Immunofluorescence showed an intense co-localization of AMH and AMHRII in
      placenta and fetal membranes. DISCUSSION: The present study for the first time
      demonstrated that human placenta and fetal membranes expresses and co-localizes
      AMH and AMHRII. Although no sex-related difference was found for the mRNA
      expression both in placenta and fetal membranes, a most intense staining for AMH
      in male fetal membranes supports AMH as a gender specific hormone.

PMID- 25972078
TI  - Green fluorescent protein nanopolygons as monodisperse supramolecular assemblies
      of functional proteins with defined valency.
AB  - Supramolecular protein assemblies offer novel nanoscale architectures with
      molecular precision and unparalleled functional diversity. A key challenge,
      however, is to create precise nano-assemblies of functional proteins with both
      defined structures and a controlled number of protein-building blocks. Here we
      report a series of supramolecular green fluorescent protein oligomers that are
      assembled in precise polygonal geometries and prepared in a monodisperse
      population. Green fluorescent protein is engineered to be self-assembled in cells
      into oligomeric assemblies that are natively separated in a single-protein
      resolution by surface charge manipulation, affording monodisperse protein
      (nano)polygons from dimer to decamer. Several functional proteins are
      multivalently displayed on the oligomers with controlled orientations. Spatial
      arrangements of protein oligomers and displayed functional proteins are directly
      visualized by a transmission electron microscope. By employing our functional
      protein assemblies, we provide experimental insight into multivalent protein
      protein interactions and tools to manipulate receptor clustering on live cell
      surfaces. 

PMID- 25972077
TI  - Inflammation in maternal obesity and gestational diabetes mellitus.
AB  - BACKGROUND: The prevalence of maternal obesity is rising rapidly worldwide and
      constitutes a major obstetric problem, increasing mortality and morbidity in both
      mother and offspring. Obese women are predisposed to pregnancy complications such
      as gestational diabetes mellitus (GDM), and children of obese mothers are more
      likely to develop cardiovascular and metabolic disease in later life. Maternal
      obesity and GDM may be associated with a state of chronic, low-grade inflammation
      termed "metainflammation", as opposed to an acute inflammatory response. This
      inflammatory environment may be one mechanism by which offspring of obese women
      are programmed to develop adult disorders. METHODS: Herein we review the evidence
      that maternal obesity and GDM are associated with changes in the maternal, fetal
      and placental inflammatory profile. RESULTS: Maternal inflammation in obesity and
      GDM may not always be associated with fetal inflammation. CONCLUSION: We propose
      that the placenta 'senses' and adapts to the maternal inflammatory environment,
      and plays a central role as both a target and producer of inflammatory mediators.
      In this manner, maternal obesity and GDM may indirectly program the fetus for
      later disease by influencing placental function.

PMID- 25972079
TI  - Unusual location of the Libman-Sacks endocarditis in a teenager: a case report.
AB  - Libman-Sacks endocarditis may be the first manifestation of systemic lupus
      erythematosus. The risk of its occurrence increases with the co-existence of the
      anti-phospholipid syndrome. Changes usually involve the mitral valve and the
      aortic valve. In this report, we present a case of Libman-Sacks endocarditis of
      the tricuspid valve in a teenage girl. 

PMID- 25972080
TI  - Pulmonary metastasis in a patient with simultaneous bladder cancer and relapsing
      granulomatosis with polyangiitis.
AB  - BACKGROUND: Granulomatosis with polyangiitis (GPA) relapse can complicate the
      differential diagnosis of pulmonary lesions. CASE REPORT: A 70-year-old male
      smoker with GPA and emphysema presented with dyspnea, dry cough, and a right
      upper lobe pulmonary ground-glass opacity that persisted despite antibiotics. A
      trans-bronchial biopsy did not reveal active vasculitis, malignancy, or
      infection. He was treated for presumed GPA relapse based on pulmonary
      manifestations, renal failure, and elevated PR3-ANCA. Later, hematuria led to the
      cystoscopic discovery of a bladder wall lesion, which was diagnosed as
      micropapillary urothelial carcinoma not involving the muscularis propria. The
      patient developed an increasing pulmonary infiltrate with a new solid component,
      satellite lesions, and regional lymphadenopathy. A right upper lobe wedge
      resection showed metastatic urothelial carcinoma. CONCLUSIONS: The simultaneous
      presentation of a pulmonary lesion and GPA relapse is a diagnostic challenge. The
      differential diagnosis should include the rare possibility of metastatic
      urothelial carcinoma, regardless of how the lesion appears radiographically.

PMID- 25972081
TI  - Platelet rich fibrin combined with decalcified freeze-dried bone allograft for
      the treatment of human intrabony periodontal defects: a randomized split mouth
      clinical trail.
AB  - OBJECTIVE: Polypeptide growth factors of platelet rich fibrin (PRF) have the
      potential to regenerate periodontal tissues. Osteoinductive property of
      demineralized freeze-dried bone allograft (DFDBA) has been successfully utilized
      in periodontal regeneration. The aim of the present randomized, split mouth,
      clinical trial was to determine the additive effects of PRF with a DFDBA in the
      treatment of human intrabony periodontal defects. MATERIALS AND METHODS: Sixty
      interproximal infrabony defects in 30 healthy, non-smoker patients diagnosed with
      chronic periodontitis were randomly assigned to PRF/DFDBA group or the
      DFDBA/saline. Clinical [pocket depth (PD), clinical attachment level (CAL) and
      gingival recession (REC)] and radiographic (bone fill, defect resolution and
      alveolar crest resorption) measurements were made at baseline and at a 12-month
      evaluation. RESULTS: Compared with baseline, 12-month results indicated that both
      treatment modalities resulted in significant changes in all clinical and
      radiographic parameters. However, the PRP/DFDBA group exhibited statistically
      significantly greater changes compared with the DFDBA/saline group in PD (4.15 +/
      0.84 vs 3.60 +/- 0.51 mm), CAL (3.73 +/- 0.74 vs 2.61 +/- 0.68 mm), REC (0.47 +/
      0.56 vs 1.00 +/- 0.61 mm), bone fill (3.50 +/- 0.67 vs 2.49 +/- 0.64 mm) and
      defect resolution (3.73 +/- 0.63 vs 2.75 +/- 0.57 mm). CONCLUSION: Observations
      indicate that a combination of PRF and DFDBA is more effective than DFDBA with
      saline for the treatment of infrabony periodontal defects.

PMID- 25972082
TI  - Possible association of proinflammatory cytokines including IL1beta and TNFalpha
      with enhanced Th17 cell differentiation in patients with Behcet's disease.
AB  - We have reported that helper T type 17 (Th17) cells increased in patients with
      Behcet's disease (BD). It remains obscure how Th17 cells increase in the
      patients. We here analyzed whether T cells preferentially differentiate into Th17
      cells in response to various inflammatory cytokines in patients with BD.
      Exogenous interleukin (IL)23 sustained the higher Th17 cell frequencies of
      CD4+CD45RO+ T cells after a 2-day culture in vitro in patients with BD, whereas
      the T cell subpopulation of normal individuals did not respond to IL23 to
      sustain/increase Th17 cell frequencies. IL23 receptor positive cell frequencies
      in freshly isolated BD CD4+CD45RO+ T cells correlated with Th17 cell frequencies
      assessed by intracellular cytokine staining. After a 2-day culture with IL23, BD
      CD4+ T cells retained the correlation between IL23 receptor expression level and
      extent of IL17 secretion (as indicated by Th17 cell frequencies), whereas such
      correlation was not noted in normal individuals. IL23 signals with its receptor
      were thus suggested to induce IL17 secretion (Th17 cell frequencies) in a short
      time culture in patients with BD. We cultured CD4+CD45RO- T cells for 11 days
      with various inflammatory cytokines to study which cytokine associated with the
      enhanced Th17 frequencies in the patients. IL17 production by CD4+CD45RO- T cells
      of BD patients increased significantly by the supplementation of IL1beta and
      tumor necrosis factor (TNF)alpha, in addition to IL23, compared with that of
      normal individuals. These results suggest that proinflammatory cytokines, such as
      IL1beta, TNFalpha, and IL23, may associate with the expansion of Th17 cells in
      patients with BD. This study was registered with the University Hospital Medical
      Information Network-Clinical Trials Registry (UMIN000003806). 

PMID- 25972083
TI  - Development of a real-time reverse transcription loop-mediated isothermal
      amplification method for the rapid detection of porcine epidemic diarrhea virus.
AB  - BACKGROUND: Porcine epidemic diarrhea (PED) is an acute and highly contagious
      enteric disease characterized by severe enteritis, vomiting and watery diarrhea
      in swine. Recently, the outbreak of the epidemic disease has been a serious
      problem in swine industry. The objective of this study is to develop a rapid,
      sensitive, and real-time reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) method for the detection of porcine epidemic diarrhea
      virus (PEDV) in less equipped laboratories. RESULTS: The optimal reaction
      condition of the current real-time RT-LAMP for PEDV was 62  degrees C for 45 min.
      It was capable of detecting PEDV from clinical samples and differentiating PEDV
      from several related porcine viruses, while it did not require additional
      expensive equipment. The minimum detection limit of the real-time RT-LAMP assay
      was 0.07PFU per reaction for PEDV RNA, making this assay approximately 100-fold
      more sensitive than that of one-step RT-PCR. By screening a panel of clinical
      specimens, the results showed that this method presented a similar sensitivity
      with real-time RT-PCR and was somewhat sensitive than one-step RT-PCR in
      detection of clinical samples. CONCLUSIONS: In this study, we have developed a
      new real-time RT-LAMP method, which is rapid, sensitive and efficient to detect
      PEDV.This method holds great promises not only in laboratory detection and
      discrimination of PEDV but also in large scale field and clinical studies.

PMID- 25972085
TI  - Effects of gender and executive function on visuospatial working memory in adult
      obsessive-compulsive disorder.
AB  - Visuospatial working memory (VSWM) is the ability of the brain to transiently
      store and manipulate visual information. VSWM deficiencies have been reported in
      obsessive-compulsive disorder (OCD), but not consistently, perhaps due to
      variability in task design and clinical patient factors. To explore this
      variability, this study assessed effects of the design factors task difficulty
      and executive organizational strategy and of the clinical factors gender, OCD
      symptom dimension, and duration of illness on VSWM in OCD. The CANTAB spatial
      working memory, spatial recognition memory, delayed matching to sample, and stop
      signal tasks were administered to 42 adult OCD patients and 42 age- and sex
      matched healthy controls. Aims were to detect a possible VSWM deficit in the OCD
      sample, to evaluate influences of the above task and patient factors, to
      determine the specificity of the deficit to the visuospatial subdomain, and to
      examine effects of sustained attention as potential neurocognitive confound. We
      confirmed previous findings of a VSWM deficit in OCD that was more severe for
      greater memory load (task difficulty) and that was affected by task strategy
      (executive function). We failed to demonstrate significant deficits in
      neighboring or confounding neurocognitive subdomains (visual object recognition
      or visual object short-term memory, sustained attention). Notably, the VSWM
      deficit was only significant for female patients, adding to evidence for sexual
      dimorphism in OCD. Again as in prior work, more severe OCD symptoms in the
      symmetry dimension (but no other dimension) significantly negatively impacted
      VSWM. Duration of illness had no significant effect on VSWM. VSWM deficits in OCD
      appear more severe with higher task load and may be mediated through poor task
      strategy. Such deficits may present mainly in female patients and in (male and
      female) patients with symmetry symptoms.

PMID- 25972086
TI  - The impact of professional and organizational identification on the relationship
      between hospital-physician exchange and customer-oriented behaviour of
      physicians.
AB  - BACKGROUND: Hospitals face increasingly competitive market conditions. In this
      challenging environment, hospitals have been struggling to build high-quality
      hospital-physician relationships. In the literature, two types of managerial
      strategies for optimizing relationships have been identified. The first focuses
      on optimizing the economic relationship; the second focuses on the noneconomic
      dimension and emphasizes the cooperative structure and collaborative nature of
      the hospital-physician relationship. We investigate potential spillover effects
      between the perceptions of physicians of organizational exchange and their
      customer-oriented behaviors. METHODS: A cross-sectional study was conducted on
      130 self-employed physicians practicing at six Belgian hospitals. Economic
      exchange was measured using the concept of distributive justice (DJ); noneconomic
      exchange was measured by the concept of perceived organizational support (POS).
      Our outcomes consist of three types of customer-oriented behaviours: internal
      influence (II), external representation (ER), and service delivery (SD). RESULTS:
      Our results show a positive relationship between DJ and II (adjusted R(2) =
      0.038, t = 2.35; p = 0.028) and ER (adjusted R(2) = 0.15, t = 4.59; p < 0.001)
      and a positive relationship between POS and II (adjusted R(2) = 0.032, t = 2.26;
      p = 0.026) and ER (adjusted R(2) = 0.22, t = 5.81; p < 0.001). No relationship
      was present between DJ (p = 0.54) or POS (p = 0.57) and SD. Organizational
      identification positively moderates the relationship between POS and ER (p =
      0.045) and between DJ and ER (p = 0.056). The relationships between POS and II (p
      = 0.54) and between DJ and II (p = 0.99) were not moderated by OI. Professional
      identification did not moderate the studied relationships. CONCLUSION: Our
      results demonstrate that both perceptions of economic and noneconomic exchange
      are important to self-employed physicians' customer-oriented behaviours.
      Fostering organizational identification could enhance this reciprocity dynamic.

PMID- 25972084
TI  - Restin suppressed epithelial-mesenchymal transition and tumor metastasis in
      breast cancer cells through upregulating mir-200a/b expression via association
      with p73.
AB  - BACKGROUND: Restin belongs to MAGE superfamily and is known as MAGE H1. Restin
      was firstly cloned from HL-60 cells treated with all-trans retinoic acid (ATRA).
      Previous studies showed a pro-apoptotic role of Restin in several cell lines.
      However, little information is available on its expression patterns and functions
      in vivo. Our study was performed to detect if Restin plays a role in breast
      cancer cells in vitro and in vivo. METHODS AND RESULTS: Real-time PCR and western
      blot were conducted to detect Restin expression in multiple breast cancer cell
      lines and Restin level was negatively related with cell motility. Restin
      overexpression and knockdown stable cell lines were established by transducing
      lentivirus into MCF-7 and MDA-MB-231 cells. Cell morphology, wound closure assay,
      transwell migration and invasion assays were performed to detect if Restin
      inhibited EMT. Our data showed that Restin overexpressed cells exhibited
      classical epithelial cell morphology, and Restin overexpression resulted in
      activation of epithelial markers and suppression of mesenchymal markers, and
      inhibition of cell migration and invasion. Tumor xenograft model was used to
      characterize the biological functions of Restin in vivo. We found that Restin
      overexpression led to reduced lung metastasis. Real-time PCR, western blot,
      luciferase assay and ChIP assay were performed to identify the potential targets
      of Restin and the underlying molecular mechanisms. Among several master
      regulators of EMT, only ZEB1/2 levels were dramatically inhibited by Restin.
      Unexpectedly, Restin indirectly regulated ZEB1/2 expression at post
      transcriptional level. We further identified mir-200a/b, well-characterized
      mediators controlling ZEB1/2 expression, were transcriptionally activated by
      Restin and the regulation was dependent on the p53 binding site in mir-200b/a/429
      promoter. Further mechanical studies demonstrated Restin interacted with p73, one
      of p53 family members, which contributed to Restin-mediated activation of mir
      200a/b and suppression of ZEB1/2. CONCLUSIONS: Taken together, our results
      suggest that Restin inhibits EMT and tumor metastasis by controlling the
      expression of the tumor metastasis suppressor mir-200a/b via association with
      p73. Our findings not only establish a mechanistic link between Restin, EMT and
      tumor metastasis, but also provide strong evidence supporting the notion that
      MAGE Group II proteins may exert a tumor suppressive effect in vivo.

PMID- 25972087
TI  - Lactic acid bacteria and their controversial role in fresh meat spoilage.
AB  - Lactic acid bacteria (LAB) constitute a heterogeneous group that has been widely
      associated with fresh meat and cooked meat products. They represent a
      controversial cohort of microbial species that either contribute to spoilage
      through generation of offensive metabolites and the subsequent organoleptic
      downgrading of meat or serve as bioprotective agents with strains of certain
      species causing unperceivable or no alterations. Therefore, significant
      distinction among biotypes is substantiated by studies determining spoilage
      potential as a strain-specific trait corroborating the need to revisit the
      concept of spoilage. 

PMID- 25972089
TI  - p21 Exploits Residue Tyr151 as a Tether for High-Affinity PCNA Binding.
AB  - Proliferating cell nuclear antigen (PCNA, processivity factor, sliding clamp) is
      a ring-shaped protein that tethers proteins to DNA in processes, including DNA
      replication, DNA repair, and cell-cycle control. Often used as a marker for cell
      proliferation, PCNA is overexpressed in cancer cells, making it an appealing
      pharmaceutical target. PCNA interacts with proteins through a PCNA interacting
      protein (PIP)-box, an eight-amino acid consensus sequence; different binding
      partners display a wide range of affinities based on function. Of all biological
      PIP-boxes, p21 has the highest known affinity for PCNA, allowing for inhibition
      of DNA replication and cell growth under cellular stress. As p21 is one of the
      few PIP-box sequences to contain a tyrosine rather than a phenylalanine in the
      eighth conserved position, we probed the significance of the hydroxyl group at
      this position using a mutational approach. Here we present the cocrystal
      structure of PCNA bound to a mutant p21 PIP-box peptide, p21Tyr151Phe, with
      associated isothermal titration calorimetry data. The p21Tyr151Phe peptide showed
      a 3-fold difference in affinity, as well as differences in entropy and enthalpy
      of binding. These differences can be attributed to a loss of hydrogen bonding
      capacity, as well as structural plasticity in the PCNA interdomain connector loop
      and the hydrophobic cavity of PCNA to which p21 binds. Thus, the hydroxyl group
      of Tyr151 in p21 acts as a tethering point for ideal packing and surface
      recognition of the peptide interface, increasing the binding affinity of p21 for
      PCNA. 

PMID- 25972088
TI  - ISOpureR: an R implementation of a computational purification algorithm of mixed
      tumour profiles.
AB  - BACKGROUND: Tumour samples containing distinct sub-populations of cancer and
      normal cells present challenges in the development of reproducible biomarkers, as
      these biomarkers are based on bulk signals from mixed tumour profiles. ISOpure is
      the only mRNA computational purification method to date that does not require a
      paired tumour-normal sample, provides a personalized cancer profile for each
      patient, and has been tested on clinical data. Replacing mixed tumour profiles
      with ISOpure-preprocessed cancer profiles led to better prognostic gene
      signatures for lung and prostate cancer. RESULTS: To simplify the integration of
      ISOpure into standard R-based bioinformatics analysis pipelines, the algorithm
      has been implemented as an R package. The ISOpureR package performs analogously
      to the original code in estimating the fraction of cancer cells and the patient
      cancer mRNA abundance profile from tumour samples in four cancer datasets.
      CONCLUSIONS: The ISOpureR package estimates the fraction of cancer cells and
      personalized patient cancer mRNA abundance profile from a mixed tumour profile.
      This open-source R implementation enables integration into existing computational
      pipelines, as well as easy testing, modification and extension of the model.

PMID- 25972090
TI  - Re: Fitzgerald et al. "Eligibility for low-dose computerized tomography screening
      among asbestos-exposed individuals".

PMID- 25972091
TI  - Opioids for agitation in dementia.
AB  - BACKGROUND: Agitation is a common experience for people living with dementia,
      particularly as day-to-day function and cognition start to decline more. At the
      present time there are limited pharmacological options for relieving agitation
      and little is known about the safety and efficacy of opioid drugs in this
      setting. OBJECTIVES: To determine the clinical efficacy and safety of opioids for
      agitation in people with dementia. SEARCH METHODS: We searched ALOIS, the
      Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13
      June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR
      buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR
      dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil
      OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone
      OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR
      hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR
      dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials
      identified from monthly searches of a number of major healthcare databases such
      as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey
      literature sources. SELECTION CRITERIA: Randomised, controlled trials of opioids
      compared to placebo for agitation in people with dementia. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed the studies identified by the search
      against the inclusion criteria. MAIN RESULTS: There are currently no completed
      randomised, placebo controlled trials of opioids for agitation in dementia. There
      are two potentially relevant trials still in progress. AUTHORS' CONCLUSIONS: We
      found insufficient evidence to establish the clinical efficacy and safety of
      opioids for agitation in people with dementia. There remains a lack of data to
      determine if or when opioids either relieve or exacerbate agitation. More
      evidence is needed to guide the effective, appropriate and safe use of opioids in
      dementia.

PMID- 25972092
TI  - Paeoniflorin Protects against Nonalcoholic Fatty Liver Disease Induced by a High
      Fat Diet in Mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease
      worldwide. Paeoniflorin, a natural product and active ingredient of Paeonia
      lactiflora, has been demonstrated to have many pharmacological effects including
      antiinflammatory and antihyperglycemic activity. We investigated the effects of
      paeoniflorin on NAFLD in mice and its underlying mechanisms. We examined this
      hypothesis using a well-established animal model of NAFLD. The effects of
      paeoniflorin on inflammation and glucolipid metabolism disorder were evaluated.
      The corresponding signaling pathways were measured using real-time polymerase
      chain reaction (PCR). We demonstrated that the mice developed obesity,
      dyslipidemia, and fatty liver, which formed the NAFLD model. Paeoniflorin
      attenuated NAFLD and exhibited potential cardiovascular protective effects in
      vivo by lowering body weight, hyperlipidemia, and insulin resistance; blocking
      inflammation; and inhibiting lipid ectopic deposition. Further investigation
      revealed that the antagonistic effect on hyperlipidemia and lipid ectopic
      deposition was related to lowering the lipid synthesis pathway (de novo pathway,
      3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoAR)), promoting fatty
      acid oxidation [peroxisome proliferator-activated receptor-alpha (PPARalpha),
      carnitine palmitoyltransferase-1, etc.] and increasing cholesterol output
      (PPARgamma-liver X receptor-alpha-ATP-binding cassette transporter-1); the
      inhibitory effects on inflammation and hyperglycemia were mediated by blocking
      inflammatory genes activation and reducing gluconeogenic genes expression
      (phosphoenolpyruvate carboxykinase and G6Pase). These results suggest that
      paeoniflorin prevents the development of NAFLD and reduces the risks of
      atherosclerosis through multiple intracellular signaling pathways. It may
      therefore be a potential therapeutic compound for NAFLD. 

PMID- 25972093
TI  - Arterial stiffness in periodontitis patients and controls. A case-control and
      pilot intervention study.
AB  - Increased arterial stiffness (AS) is an important indicator for atherosclerotic
      cardiovascular disease (ACVD). Epidemiologically, periodontitis and ACVD are
      associated. Therefore, we aimed to investigate AS in periodontitis patients and
      controls. In addition, we explored the effect of periodontal therapy on AS in a
      sub-group of cases. Pulse-wave velocity (PWV), a non-invasive chair-side function
      test for AS, was measured in periodontitis patients (n=57; mean age 46.6 years)
      and compared with a reference group (n=48; mean age 45.5 years). In addition, 45
      cases (mean age 46.9 years) were 6 months followed after periodontal treatment,
      to explore a possible effect on arterial function. Periodontitis patients showed
      a significantly increased PWV compared with the reference group (8.01+/-0.20 vs.
      7.36+/-0.22 m s(-1) respectively; P=0.029) and this remained significant after
      adjustments for ACVD risk factors (P=0.019). After periodontal therapy, no
      significant reduction in PWV was seen (8.00+/-1.8 to 7.82+/-1.6 m s(-1); P=0.13),
      but systolic blood pressure (SBP) was significantly reduced (119.8+/-14.6 to
      116.9+/-15.1 mm Hg; P=0.040). It can be concluded that periodontitis is
      associated with increased AS. This confirms with a new parameter the association
      of periodontitis with ACVD. Although periodontal treatment did not lower AS
      significantly, a modest reduction of SBP after 6 months was observed.

PMID- 25972094
TI  - Using web-based training to enhance perceptual-cognitive skills in complex
      dynamic offside events.
AB  - In association football, the difficulty in making offside decisions depends on
      both perceptual and cognitive processes. Therefore, the objectives of the present
      study were to enhance the decision-making skills of assistant referees by further
      developing their ability to (1) time slice the incoming information flow into
      series of isolated time frames during an ongoing offside situation and (2) use
      this information to mentally read off the spatial positions of the key-role
      players. Training (n = 10) and control groups (n = 10) were exposed to a pre- and
      post-test, consisting of an offside decision-making and frame recognition test.
      In the latter, assistant referees were asked to indicate which of five photos
      best represented the spatial position of the defender and attacker at the moment
      of the pass. Only the training group received 12 web-based offside training
      sessions. First, the training group improved in mentally freezing, holding and
      scanning the mental picture of the offside situation in short-term memory from
      pre- to post-test, as evidenced by an increased recognition accuracy. Second, the
      improvement in recognition accuracy resulted in enhanced performance on the
      offside decision-making task. The benefits of web-based training are highlighted.

PMID- 25972095
TI  - Local knowledge about fodder plants in the semi-arid region of Northeastern
      Brazil.
AB  - BACKGROUND: This study evaluated local knowledge of the fodder plants of the
      Caatinga in northeast Brazil (seasonal dry forest). Specifically, the goal was to
      catalog local knowledge regarding the use of native and exotic forage plants in
      two rural communities located in the state of Paraiba (northeast Brazil), to
      provide information for nutritional investigations and to verify how the
      knowledge of these resources is distributed. METHODS: The communities were
      followed for three consecutive years, and interviews were conducted with 44
      families (20 men and 24 women). Nine of these individuals were determined by the
      snowball technique to be key informants who held more specific knowledge about
      the topic. The data were structured into a database and statistically analyzed.
      RESULTS: Overall, 136 plants from 37 families and 113 genera were cited, and the
      knowledge of men was at a higher level than that of women (p < 0.05).
      Participants demonstrated a sophisticated knowledge of nutritional
      characteristics such as nutritional value, palatability, availability and
      productivity. Native plants were highlighted over the exotic, especially for
      species of the families Cactaceae, Bromeliaceae and Fabaceae. CONCLUSIONS: The
      great diversity of plants cited by the informants demonstrates the potential of
      local vegetation and the importance of traditional knowledge in the research
      process and in the characterization of forage resources. This diversity also
      favors the selection of promising species for future biotechnological
      investigations.

PMID- 25972097
TI  - Bile acid mediated effects on gut integrity and performance of early-weaned
      piglets.
AB  - BACKGROUND: Early weaning (EW) results in a transient period of impaired
      integrity of the intestinal mucosa that may be associated with reduced plasma
      concentration of glucagon-like peptide-(GLP) 2. We have previously shown that
      intragastric infusion of chenodeoxycholic acid (CDC) increases circulating GLP-2
      in early-weaned piglets. The aim of this study was to expand previous work to
      establish whether feeding piglets a cereal-based diet supplemented with CDC can
      improve gut integrity and animal performance immediately after EW. A cohort of 36
      piglets weaned at 20 days of age, 6.2 +/- 0.34 kg of body weight (BW) were
      randomly assigned (n = 18) to receive a standard prestarter diet or the same diet
      supplemented with 60 mg of CDC per kg of initial BW for ad libitum intake until
      day 14 postweaning. Thereafter, all pigs were fed the same untreated starter diet
      for 21 days until the end of the study on day 35. On days 1, 7 and 14 blood
      samples were collected from 6 pigs per treatment to measure plasma GLP-2. On day
      15, 6 pigs per treatment were euthanized to obtain intestinal tissue samples for
      later histological and gene expression analyses. RESULTS: Supplementing the diet
      with CDC tended to increase plasma GLP-2 (P < 0.07; 39 %) and the weight of the
      large intestine (P < 0.10; 11 %), and increased ileal crypt depth (P < 0.04; 15
      %) after 14 days of treatment exposure. Although feed intake and BW gain were not
      affected by treatments, feeding CDC induced the expression of the cytokines TNF
      alpha (P < 0.02; 1.9 fold), IL-6 (P < 0.01; 2.4 fold), and IL-10 (P < 0.006; 2.2
      fold) and the tight junctional protein ZON-1 (P < 0.02; 1.5 fold) in the distal
      small intestine. CONCLUSIONS: This study showed that the oral administration of
      CDC to early-weaned pigs has the potential to improve the protection of the
      intestinal mucosa independently of relevant changes in gut growth.

PMID- 25972098
TI  - Methodological implications in pH standardization of exhaled breath condensate.
AB  - The variable amount of dissolved carbon dioxide is one of the main confounding
      factors of exhaled breath condensate (EBC) pH measurements. There have been many
      attempts at identifying the optimal approach to displace CO2 as a way to gain
      reproducible and valid pH values in EBC samples. The aim of the present study was
      to assess the correlation of pH and pCO2 in untreated, neat EBC samples and,
      after deaeration, to reevaluate the standardization of CO2 as a means to obtain
      valid pH values. A further aim was to evaluate the impact of deaeration on the
      acid-base balance in EBC samples. EBC was collected from seven female and 31 male
      subjects. The pH and pCO2 values immediately determined in untreated, neat EBC
      samples were strongly correlated (rp = -0.723, p <  0.0001). This correlation was
      not observed after deaeration with argon (rs = 0.264, p = 0.109). Based on a
      regression function for the pH/pCO2 relationship, the calculated pH at a pCO2 of
      5.33 kPa was 6.07 (IQR 5.99, 6.20). No significant difference was observed
      between the pH measured in neat EBC samples and those calculated after deaeration
      with regression function and measured neat pCO2. Our data suggest that pCO2 is
      the most important confounder of pH measurement in EBC samples and, when
      adjusting for pCO2, the acid-base balance of EBC samples is not significantly
      influenced by the process of deaeration. Furthermore, measurement with a blood
      gas analyzer and standardization of pH for pCO2 allows sensitive assaying of EBC
      samples. Therefore, this method provides a basis for detection of even small
      changes in airway pH due to inhalative exposure or respiratory disease.

PMID- 25972099
TI  - Desmocollin-2 alone forms functional desmosomal plaques, with the plaque
      formation requiring the juxtamembrane region and plakophilins.
AB  - The role of the juxtamembrane region of the desmocollin-2 cytoplasmic domain in
      desmosome formation was investigated by using gene knockout and reconstitution
      experiments. When a deletion construct of the desmocollin-2 juxtamembrane region
      was expressed in HaCaT cells, the mutant protein became localized linearly at the
      cell-cell boundary, suggesting the involvement of this region in desmosomal
      plaque formation. Then, desmocollin-2 and desmoglein-2 genes of epithelial DLD-1
      cells were ablated by using the CRISPR/Cas9 system. The resultant knockout cells
      did not form desmosomes, but re-expression of desmocollin-2 in the cells formed
      desmosomal plaques in the absence of desmoglein-2 and the transfectants showed
      significant cell adhesion activity. Intriguingly, expression of desmocollin-2
      lacking its juxtamembrane region did not form the plaques. The results of an
      immunoprecipitation and GST-fusion protein pull-down assay suggested the binding
      of plakophilin-2 and -3 to the region. Ablation of plakophilin-2 and -3 genes
      resulted in disruption of the plaque-like accumulation and linear localization of
      desmocollin-2 at intercellular contact sites. These results suggest that the
      juxtamembrane region of desmocollin-2 and plakophilins are involved in the
      desmosomal plaque formation, possibly through the interaction between this region
      and plakophilins. 

PMID- 25972096
TI  - Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug
      Interactions.
AB  - Opioid-related deaths, abuse, and drug interactions are growing epidemic problems
      that have medical, social, and economic implications. Drug transporters play a
      major role in the disposition of many drugs, including opioids; hence they can
      modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug
      interactions (DDIs). Our understanding of the interaction of transporters with
      many therapeutic agents is improving; however, investigating such interactions
      with opioids is progressing relatively slowly despite the alarming number of
      opioids-mediated DDIs that may be related to transporters. This review presents a
      comprehensive report of the current literature relating to opioids and their drug
      transporter interactions. Additionally, it highlights the emergence of
      transporters that are yet to be fully identified but may play prominent roles in
      the disposition of opioids, the growing interest in transporter genomics for
      opioids, and the potential implications of opioid-drug transporter interactions
      for cancer treatments. A better understanding of drug transporters interactions
      with opioids will provide greater insight into potential clinical DDIs and could
      help improve opioids safety and efficacy. 

PMID- 25972100
TI  - Detection of Cyclospora in captive chimpanzees and macaques by a quantitative PCR
      based mutation scanning approach.
AB  - BACKGROUND: Cyclospora is a protistan parasite that causes enteritis in several
      species of animals including humans. The aim of this study was to investigate the
      presence of Cyclospora in captive non-human primates. METHODS: A total of 119
      faecal samples from Pan troglodytes, Macaca sylvanus, Cercopithecus cephus,
      Erythrocebus patas, Chlorocebus aethiops and Macaca fascicularis from a wildlife
      animal rescue center as well as from Macaca fascicularis from an experimental
      primate research center were tested for the presence of Cyclospora by
      quantitative real-time PCR (qPCR) and single-strand conformation polymorphism
      (SSCP) analysis. RESULTS: Cyclospora was detected in three Pan troglodytes
      (13.6%) and nine (9.3%) Macaca fascicularis. CONCLUSIONS: The present study
      represents the first record of Cyclospora in captive primates in Europe,
      suggesting the presence of Cyclospora cayetanensis, which is transmissible to
      humans.

PMID- 25972103
TI  - Direct monitoring of ultrafast electron and hole dynamics in perovskite solar
      cells.
AB  - Organic-inorganic hybrid perovskite solar cells have emerged as cost effective
      efficient light-to-electricity conversion devices. Unravelling the time scale and
      the mechanisms that govern the charge carrier dynamics is of paramount importance
      for a clear understanding and further optimization of the perovskite based
      devices. For the classical FTO/bulk titania blocking layer/mesoporous
      titania/perovskite/Spiro-OMeTAD (FTO/TPS) cell, further detailed and systematic
      studies of the ultrafast events related to exciton generation, electron and hole
      transfer, ultrafast relaxation are still needed. We characterize the initial
      ultrafast processes attributed to the exciton-perovskite lattice interactions
      influenced by charge transfer to the electron and hole transporters that precede
      the exciton diffusion into free charge carriers occurring in the sensitizer. Time
      resolved transient absorption studies of the FTO/perovskite and FTO/TPS samples
      under excitation at different wavelengths and at low fluence 2 (MUJ cm(-2))
      indicate the sub-picosecond electron and hole injection into titania and Spiro
      OMeTAD, respectively. Furthermore, the power-dependent femtosecond transient
      absorption measurements support the ultrafast charge transfer and show strong
      Auger-type multiparticle interactions at early times. We reveal that the decays
      of the internal trap states are the same for both films, while those at surfaces
      differ. The contribution of the former in the recombination is small, thus
      increasing the survival probability of the charges in the excited perovskite. 

PMID- 25972101
TI  - Wound Infections Following Implant removal below the knee: the effect of
      antibiotic prophylaxis; the WIFI-trial, a multi-centre randomized controlled
      trial.
AB  - BACKGROUND: In the Netherlands about 18,000 procedures with implant removal are
      performed annually following open or closed reduction and fixation of fractures,
      of which 30-80% concern the foot, ankle and lower leg region. For clean surgical
      procedures, the rate of postoperative wound infections (POWI) should be less than
      ~2%. However, rates of 10-12% following implant removal have been reported,
      specifically after foot, ankle and lower leg fractures. Currently, surgeons
      individually decide if antibiotics prophylaxis is given, since no guideline
      exists. This leads to undesirable practice variation. The aim of the study is to
      assess the (cost-)effectiveness of a single intravenous gift of Cefazolin prior
      to implant removal following surgical fixation of foot, ankle and/or lower leg
      fractures. METHODS: This is a double-blind randomized controlled trial in
      patients scheduled for implant removal following a foot, ankle or lower leg
      fracture. Primary outcome is a POWI within 30 days after implant removal.
      Secondary outcomes are quality of life, functional outcome and costs at 30 days
      and 6 months after implant removal. With 2 x 250 patients a decrease in POWI rate
      from 10% to 3.3% (expected rate in clean-contaminated elective orthopaedic trauma
      procedures) can be detected (Power = 80%, 2-sided alpha = 5%, including 15% lost
      to follow up). DISCUSSION: If administration of prophylactic antibiotics prior to
      implant removal reduces the infectious complication rate, this will offer a
      strong argument to adopt this as standard practice of care. This will
      consequently lead to less physical and social disabilities and health care use. A
      preliminary, conservative estimation suggests yearly cost savings in the
      Netherlands of ? 3.5 million per year. TRIAL REGISTRATION: This study is
      registered at Clinicaltrials.gov ( NCT02225821 ) and the Netherlands Trial
      Register ( NTR4393 ) and was granted permission by the Medical Ethical Review
      Committee of the Academic Medical Centre on October 7 2014.

PMID- 25972104
TI  - Home-based management of severely acute malnutrition: feasibility of ethically
      designed, community-based randomised clinical trials.
AB  - The Indian Council of Medical Research had, on May 31, 2011, called for research
      proposals on severely acute malnourished (SAM) children to generate evidence for
      the development of practical and scalable regimens to medically rehabilitate
      children suffering from SAM, without serious complications, at the home/community
      level and/or peripheral inpatient facilities. The primary outcomes of the
      proposed research study are recovery from SAM in the short term, as well as
      sustenance of recovery (for at least six months after the initiation of
      treatment). The secondary outcomes are the acceptability, feasibility and safety
      of the regimes being tested. It was suggested that the studies be designed as
      individual or cluster randomised or quasi randomised controlled trials (RCTs).
      This paper analyses the methodological, operational, and most importantly,
      ethical challenges and implications of conducting community-based RCTs involving
      SAM children. The paper dwells in detail on why and how the RCT design is
      inappropriate and unsuitable for studying the effectiveness of home-based
      management of SAM children in the community. 

PMID- 25972105
TI  - Coexistence of two clades of enterovirus D68 in pediatric Swedish patients in the
      summer and fall of 2014.
AB  - In 2014, an outbreak of enterovirus D68 (EV-D68) was observed in North America,
      with cases of severe respiratory illness and a possible etiological link to cases
      of acute flaccid paralysis. EV-D68 has also been reported from European
      countries, but no data from Sweden are available. This study investigated
      respiratory specimens collected during July-October 2014 from 30 Swedish children
      aged 0-9 years who were positive for enterovirus and/or rhinovirus in routine
      clinical PCR. Seven samples were typed as EV-D68 by VP4/VP2 sequencing. Two
      genetically distinct EV-D68 variants coexisted. Six viruses belonged to clade B,
      the variant involved in the North American outbreak, and one virus belonged to
      clade A. Respiratory illness was the major symptom among EV-D68 infected patients
      and all fully recovered. This is the first report of EV-D68 in Sweden.
      Considering the current epidemiological situation, genotyping and specific EV-D68
      testing should be considered in patients with severe respiratory illness who test
      positive for enterovirus or rhinovirus in routine diagnostics. 

PMID- 25972107
TI  - Large Deformation Properties of Red Blood Cell Membrane Based on a Higher Order
      Gradient Quasi-continuum Model.
AB  - Based on the proposed higher order gradient quasi-continuum model, the numerical
      investigations of the basic mechanical properties and deformation behaviors of
      human red blood cell (RBC) membrane under large deformation at room temperature
      (i.e., 300 K) are carried out in the present paper. The results show that RBC
      membrane is a nonlinear hyperelastic material. The mechanical properties of RBC
      membrane is dominated by isotropic nature at the stage of initial deformation,
      however, its anisotropic material properties emerge clearly with the loading
      increasing. The out-of-plane wrinkling of RBC membrane upon shear loading can be
      reproduced numerically. With the use of the so-called higher order Cauchy-Born
      rule as the kinematic description, the bending stiffness of RBC membrane can be
      considered conveniently.

PMID- 25972108
TI  - Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis,
      regardless of the presence of obesity.
AB  - Psoriasis is an autoimmune disease associated with the production of pro
      inflammatory cytokines. The identification of these molecules in the pathogenesis
      of psoriasis facilitated the use of monoclonal antibodies to block their actions
      as a treatment for severe psoriasis. An increased inflammatory response has been
      documented in patients with obesity, a condition that is associated with the
      occurrence and severity of psoriasis. Osteopontin (OPN), TNF and CXCL9 levels are
      enhanced in patients with psoriasis, although OPN has been documented in the
      adipose tissue of obese patients without psoriasis. The prevalence of obesity is
      much higher in psoriasis patients compared with the general population. Thus, we
      aimed to evaluate the relationship between cytokine levels and psoriasis in the
      context of obesity. We compared OPN and CXCL9 plasma levels among 117 psoriasis
      patients and 27 healthy body mass index-matched subjects using ELISA. We also
      analyzed the TNF, CCL2 and CCL5 levels in a smaller subgroup of patients and
      matched controls. Median OPN, CCL5 and CXCL9 levels were significantly higher in
      psoriasis patients compared with the controls, independent of obesity. There was
      no difference between the median CCL2 levels in the psoriasis patients and the
      controls (P<0.05), although the CCL2 levels were elevated in obese patients
      compared with non-obese psoriasis patients (P<0.001). Facial involvement and the
      psoriasis area severity index (PASI) score were not associated (P<0.05) with OPN
      levels or elevated levels of chemokines. There was no significant correlation
      between the OPN and CXCL9 levels or the OPN and TNF levels in psoriasis patients.
      This work confirms that OPN, CCL5 and CXCL9 plasma levels are higher in psoriasis
      patients and provides evidence that their higher levels are not a consequence of
      obesity. Furthermore, the results demonstrate that OPN production is independent
      of TNF-alpha and CXCL9. 

PMID- 25972106
TI  - Voltage Sensing in Membranes: From Macroscopic Currents to Molecular Motions.
AB  - Voltage-sensing domains (VSDs) are integral membrane protein units that sense
      changes in membrane electric potential, and through the resulting conformational
      changes, regulate a specific function. VSDs confer voltage-sensitivity to a large
      superfamily of membrane proteins that includes voltage-gated Na[Formula: see
      text], K[Formula: see text], Ca[Formula: see text] ,and H[Formula: see text]
      selective channels, hyperpolarization-activated cyclic nucleotide-gated channels,
      and voltage-sensing phosphatases. VSDs consist of four transmembrane segments
      (termed S1 through S4). Their most salient structural feature is the highly
      conserved positions for charged residues in their sequences. S4 exhibits at least
      three conserved triplet repeats composed of one basic residue (mostly arginine)
      followed by two hydrophobic residues. These S4 basic side chains participate in a
      state-dependent internal salt-bridge network with at least four acidic residues
      in S1-S3. The signature of voltage-dependent activation in electrophysiology
      experiments is a transient current (termed gating or sensing current) upon a
      change in applied membrane potential as the basic side chains in S4 move across
      the membrane electric field. Thus, the unique structural features of the VSD
      architecture allow for competing requirements: maintaining a series of stable
      transmembrane conformations, while allowing charge motion, as briefly reviewed
      here. 

PMID- 25972111
TI  - Delayed Parkinsonism after acute chorea due to non-ketotic hyperglycemia.

PMID- 25972109
TI  - Advanced paternal age and risk of psychotic-like symptoms in adult offspring.
AB  - Between 2% and 12% of adults in the general population report experiencing
      psychotic-like symptoms, and there is suggestive evidence that these symptoms are
      associated with risk of schizophrenia and other forms of psychopathology. Older
      parental age is an established risk factor for schizophrenia, however few studies
      have attempted to extend this relationship to psychotic-like symptoms. Data come
      from the National Comorbidity Survey-Replication and analysis is restricted to a
      subset of respondents who completed questions on psychosis (N=924). Lifetime
      occurrence of six psychotic-like symptoms (i.e., see a vision others couldn't
      see, hear voices others couldn't hear) was assessed by self-report. These
      symptoms were combined into a single binary (any vs. none) variable and analyzed
      using logistic regression, accounting for the complex survey design. Models were
      adjusted for age, sex, race/ethnicity, socioeconomic status, marital status,
      birth order, and history of mood, anxiety, and substance use disorders.
      Approximately 9% (n=103) of respondents reported at least one psychotic-like
      symptom. In fully-adjusted models, paternal age was significantly associated with
      experiencing psychotic-like symptoms (chi(2)=13.34, p=.010). Relative to
      respondents whose fathers were aged 25 to 29 at the time of their birth, those
      with fathers aged >35 had 2.12 times higher odds (95% confidence interval: 1.08
      4.16) of psychotic-like symptoms. There was no relationship between maternal age
      (younger or older) and psychotic-like symptoms (chi(2)=0.54, p=.909). Older
      paternal, but not maternal, age at birth is associated with psychotic-like
      symptoms in adult offspring. 

PMID- 25972110
TI  - The impact of HER2 phenotype of circulating tumor cells in metastatic breast
      cancer: a retrospective study in 107 patients.
AB  - BACKGROUND: In metastatic breast cancer (MBC), antigen profiles of metastatic
      tissue and primary tumor differ in up to 20 % of patients. Reassessment of
      predictive markers, including human epidermal growth factor receptor 2 (HER2)
      expression, might help to optimize MBC treatment. While tissue sampling is
      invasive and often difficult to repeat, circulating tumor cell (CTC) analysis
      requires only a blood sample and might provide an easy-to-repeat, real-time
      "liquid biopsy" approach. The present retrospective study was conducted to
      compare HER2 expression in primary tumors, metastatic tissue, and circulating
      tumor cells (CTCs) from MBC patients and to analyze the potential impact of HER2
      overexpression by CTCs on progression-free (PFS) and overall survival (OS) in
      MBC. METHODS: CTC-positive (five or more CTCs/7.5 mL blood; CellSearch(r),
      Janssen Diagnostics) MBC patients starting a new line of systemic treatment were
      eligible for the study. HER2 status of CTCs was determined by immunofluorescence
      (CellSearch(r)). HER2 status of primary (PRIM) and metastatic (MET) tumor tissue
      was determined by immunohistochemistry. Data were analyzed using descriptive
      statistics and Kaplan-Meier plots. RESULTS: One hundred seven patients (median
      age (range) 57 (33-81) years) were included. 100/107 (93%) patients were followed
      up for a median [95% confidence interval (CI)] of 28.5 [25.1-40.1] months. Of
      37/107 (35%) CTC-HER2-positive patients only 10 (27%) were PRIM-HER2-positive.
      6/46 (13%) patients were MET-HER2-positive; only 2/10 (20%) CTC-HER2-positive
      patients were MET-HER2-positive. Overall accuracy between CTC-HER2 expression and
      PRIM-HER2 and MET-HER2 status was 69% and 74%, respectively. Kaplan-Meier plots
      of PFS and OS by CTC-HER2 status revealed significantly longer median [95% CI]
      PFS of CTC-HER2-positive versus CTC-HER2-negative patients (7.4 [4.7-13.7] versus
      4.34 [3.5-5.9] months; p = 0.035). CTC-HER2-positive status showed no significant
      difference for OS (13.7 [7.7-30.0] versus 8.7 [5.9-15.3] months; p = 0.287).
      CONCLUSIONS: HER2 status can change during the course of breast cancer. CTC
      phenotyping may serve as an easy-to-perform "liquid biopsy" to reevaluate HER2
      status and potentially guide treatment decisions. Further, prospective studies
      are needed.

PMID- 25972112
TI  - Improved identification of dystonic cervical muscles via abnormal muscle activity
      during isometric contractions.
AB  - BACKGROUND: The preferred treatment for cervical dystonia (CD) is injection of
      botulinum toxin in the dystonic muscles. Unfortunately, in the absence of
      reliable diagnostic methods it can be difficult to discriminate dystonic muscles
      from healthy muscles acting in compensation. We investigated if dystonic muscle
      activation patterns could be identified in cervical dystonia patients during a
      harmonized isometric contraction task. Furthermore, we investigated whether
      dystonia worsens at higher levels of voluntary contraction, which might further
      improve the identification of dystonic muscle activity. METHODS: An isometric
      device was used to investigate muscle activation during voluntary contraction
      tasks in 10 controls and 10 CD patients. Surface electromyography (EMG) of the
      sternocleidomastoidus, splenius capitis, and semispinalis capitis muscles was
      evaluated during a rest task and when performing submaximal (20%) and maximal
      voluntary contractions for eight head transversal force directions and for head
      twist. Two measures were developed to identify dystonic activation: 1) Muscle
      activity in the contraction direction in which the contribution of the muscle was
      lowest (Minimum EMG), and 2) the average muscle activity over all contraction
      directions (Total Mean EMG). RESULTS: Patients showed increased dystonic activity
      in the rest task and during submaximal contractions relative to controls, but not
      during maximal contractions. Increases in Minimum EMG indicated an inability of
      patients to deactivate dystonic muscles counteracting the task. Increases in
      Total Mean EMG indicated dystonic activity in all task directions. During maximal
      contractions these effects were absent in dystonic muscles. Dystonia is therefore
      found not to worsen at higher levels of isometric voluntary contraction. The
      activity of dystonic muscles modulated with different loading directions similar
      to controls. Using Minimum EMG 54% of the muscles clinically diagnosed as
      dystonic and 91% of non-dystonic muscles were predicted correctly. CONCLUSIONS:
      Dystonic muscle activity was found in cervical dystonia patients during
      submaximal contractions in all task directions using a harmonized isometric task,
      but no differences were found during maximal contractions. With some adaptation
      this method may prove useful to identify dystonic muscles.

PMID- 25972114
TI  - Inter-block information: to recover or not to recover it?
AB  - KEY MESSAGE: Comparing standard errors of treatment differences using fixed or
      random block effects with the approximation of Kackar and Harville helps in
      choosing the preferable assumption for blocks in the analysis of field
      experiments. Blocked designs are common in plant breeding field trials. Depending
      on the precision of variance estimates, recovery of inter-block information via
      random block effects may be worthwhile. A challenge in practice is to decide when
      recovery of information should be pursued. To investigate this question, a series
      of sugar beet trials laid out as alpha-designs were analysed assuming fixed or
      random block effects. Additionally, small trials laid out as alpha-designs or
      partially replicated designs were simulated and analysed assuming fixed or random
      block effects. Nine decision rules, including the Kackar-Harville adjustment,
      were used for choosing the better assumption regarding the block effects. In
      general, use of the Kackar-Harville adjustment works well and is recommended for
      partially replicated designs. For alpha-designs, using inter-block information is
      preferable for designs with four or more blocks.

PMID- 25972113
TI  - Infantile spinocerebellar ataxia type 7: Case report and a review of the
      literature.

PMID- 25972116
TI  - Distinct and common cerebral activation changes during mental time travel in
      relapsing-remitting multiple sclerosis patients.
AB  - Mental time travel (MTT) entails the ability to mentally travel into
      autobiographical memory (AM) and episodic future thinking (EFT). While AM and EFT
      share common phenomenological and cerebral functional properties, distinctive
      characteristics have been documented in healthy and clinical populations. No
      report, to our knowledge, has informed on the functional underpinnings of MTT
      impairment in multiple sclerosis (MS) patients, hence the aim of this work. We
      studied 22 relapsing-remitting MS patients and 22 matched controls. Participants
      underwent an AM/EFT assessment using the Autobiographical Interview (Levine et
      al. 2002), followed by a functional MRI session. The latter consisted in AM and
      EFT tasks, distinguishing the construction and elaboration phases of events. The
      results showed impaired performance for AM and EFT in patients, accompanied by
      increased cerebral activations mostly located in the frontal regions, which
      extended to the parietal, lateral temporal and posterior regions during AM/EFT
      tasks, relative to healthy controls. Enhanced brain activations in MS patients
      were particularly evident during the EFT task and involved the hippocampus,
      frontal, external temporal, and cingulate regions. The construction phase
      required greater fronto-parieto-temporal activations in MS patients relative to
      both healthy controls, and the elaboration phase. Taking together, our results
      suggested the occurrence of cerebral activation changes in the context of MTT in
      MS patients, expressed by distinct and common mechanisms for AM and EFT. This
      study may provide new insights in terms of cerebral activation changes in brain
      lesion and their application to clinical settings, considering AM/EFT's central
      role in everyday life. 

PMID- 25972115
TI  - Chest ultrasonography in patients with HIV: a case series and review of the
      literature.
AB  - INTRODUCTION: Pulmonary disease is common in HIV-infected patients. Diagnostic
      means, however, are often scarce in areas where most HIV patients are living.
      Chest ultrasonography has recently evolved as a highly sensitive and specific
      imaging tool for diagnosing chest conditions such as pneumothorax, pneumonia and
      pulmonary edema in critically ill patients. This article addresses the issue of
      imaging and differentiating common pulmonary conditions in HIV-infected patients
      by chest ultrasonography. METHODS: We report chest ultrasound features of five
      different common pulmonary diseases in HIV-infected patients (bacterial
      pneumonia, Pneumocystis jirovecii pneumonia, tuberculosis, cytomegalovirus
      pneumonia and non-Hodgkin lymphoma) and review the respective literature.
      CONCLUSIONS: We observed characteristic ultrasound patterns especially in
      Pneumocystis jirovecii pneumonia and pulmonary lymphoma. Further exploration of
      chest ultrasonography in HIV-infected patients appears promising and may
      translate into new diagnostic approaches for pulmonary conditions in patients
      living with HIV.

PMID- 25972117
TI  - The association between the brain and mind pops: a voxel-based morphometry study
      in 256 Chinese college students.
AB  - Mind pops or involuntary semantic memories refer to words, phrases, images, or
      melodies that suddenly pop into one's mind without any deliberate attempt to
      recall them. Despite their prevalence in everyday life, research on mind pops has
      started only recently. Notably, mind pops are very similar to clinical
      involuntary phenomena such as hallucinations in schizophrenia, suggesting their
      potential role in pathology. The present study aimed to investigate the
      relationship between mind pops and the brain morphometry measured in 302 healthy
      young adults; after exclusions, 256 participants were included in our analyses.
      Specifically, the Mind Popping Questionnaire (MPQ) was employed to measure the
      degree of individual mind pops, whereas the Voxel-Based Morphometry (VBM) was
      used to compute the volumes of both gray and white matter tissues. Multiple
      regression analyses on MPQ and VBM metrics indicated that high-frequency mind
      pops were significantly associated with smaller gray matter volume in the left
      middle temporal gyrus as well as with larger gray and white matter volume in the
      right medial prefrontal cortex. This increase in mind pops is also linked to
      higher creativity and the personality trait of 'openness'. These data not only
      suggest a key role of the two regions in generating self-related thoughts, but
      also open a possible link between brain and creativity or personality.

PMID- 25972118
TI  - Traumatic brain injury in the US military: epidemiology and key clinical and
      research programs.
AB  - Traumatic brain injury (TBI), and particularly concussion, is a major concern for
      the U.S. Military because of the associated short term disability, long term
      cognitive and pain symptoms suffered by some, and risk of prolonged or permanent
      neurologic injury if the Service member incurs a second TBI before full recovery
      from the first. Concussions were seen more often during the recent conflicts in
      Afghanistan and Iraq than in prior conflicts, such as the Vietnam War, because of
      the use of improvised explosive devices that typically caused non-penetrating
      closed head injury. Since 2000 more than 300,000 Service members were diagnosed
      with TBI, of which more than 80 % were concussions. Improved TBI screening tools
      also have identified a higher than expected incidence of concussions occurring in
      garrison. In this review we summarize current epidemiologic data for TBI in the
      Military, and describe contemporary Military procedures and strategies for TBI
      prevention, identification, evaluation, and acute and chronic care. Key TBI
      clinical research priorities and programs are described, and innovative
      organizational plans to address future TBI needs are summarized. 

PMID- 25972119
TI  - Alterations in default-mode network connectivity may be influenced by
      cerebrovascular changes within 1 week of sports related concussion in college
      varsity athletes: a pilot study.
AB  - The goal of this pilot study is to use complementary MRI strategies to quantify
      and relate cerebrovascular reactivity, resting cerebral blood flow and functional
      connectivity alterations in the first week following sports concussion in college
      varsity athletes. Seven college athletes (3F/4M, age = 19.7 +/- 1.2 years) were
      imaged 3-6 days following a diagnosed sports related concussion and compared to
      eleven healthy controls with no history of concussion (5M/6F, 18-23 years, 7
      athletes). Cerebrovascular reactivity and functional connectivity were measured
      using functional MRI during a hypercapnia challenge and via resting-state
      regional partial correlations, respectively. Resting cerebral blood flow was
      quantified using arterial spin labeling MRI methods. Group comparisons were made
      within and between 18 regions of interest. Cerebrovascular reactivity was
      increased after concussion when averaged across all regions of interest (p =
      0.04), and within some default-mode network regions, the anterior cingulate and
      the right thalamus (p < 0.05) independently. The FC was increased in the
      concussed athletes within the default-mode network including the left and right
      hippocampus, precuneus and ventromedial prefrontal cortex (p < 0.01), with
      measures being linearly related to cerebrovascular reactivity in the hippocampus
      in the concussed athletes. Significant resting cerebral blood flow changes were
      not detected between the two groups. This study provides evidence for increased
      cerebrovascular reactivity and functional connectivity in the medial regions of
      the default-mode network within days of a single sports related concussion in
      college athletes. Our findings emphasize the utility of complementary
      cerebrovascular measures in the interpretation of alterations in functional
      connectivity following concussion.

PMID- 25972120
TI  - The management of abdominal hydatidosis after the rupture of a pancreatic hydatid
      cyst: a case report.
AB  - INTRODUCTION: Echinococcosis or hydatidosis is a zoonosis caused by cestodes from
      the genus Echinococcus; its habitat is the small intestine of the definitive
      host, represented by dogs/carnivorous animals, where it produces eggs which are
      eliminated in the environment. Cystic echinococcosis represents more than 95% of
      the hydatidosis cases registered annually. The most frequent localization is the
      hepatic one, followed by the pulmonary localization with a ratio of 2.5:1. A
      pancreatic localization represents 0.2% of hydatidosis cases with a higher
      possibility of disseminating intra-abdominally. The incidence of hydatidosis in
      Romania has not been investigated yet through national studies. CASE
      PRESENTATION: We present the case of a 54-year-old Caucasian man who underwent
      emergency surgery in 1989 for symptoms suggestive for an acute abdomen. He was
      diagnosed intraoperatively with rupture of a pancreatic hydatid cyst, having a
      caudal localization and complicated by necrotic acute pancreatitis. Our objective
      is to describe a patient with hydatidosis, with unfavorable evolution after two
      surgical interventions, with intra-abdominal dissemination, for whom we
      considered the best therapeutic choice to be long-term anti-parasite drugs.
      CONCLUSIONS: He has been treated with albendazole for 6 years and he shows a very
      good tolerance; praziquantel (600 mg/week) was also administered and he is under
      clinical and biological screening. There is no general consensus on the duration
      of anti-parasite treatments.

PMID- 25972122
TI  - Small-molecule anti-inflammatory drug compositions for the treatment of asthma: a
      patent review (2013 - 2014).
AB  - INTRODUCTION: Asthma is a chronic condition affecting 235 million people
      worldwide, with prevalence continuing to increase. A significant number of
      patients have poorly controlled asthma but despite this, a new mechanistic class
      of small-molecule asthma therapy has not emerged over the past 15 years. AREAS
      COVERED: In this article, the authors review the published patent literature from
      2013 to 2014 that describes the discovery of novel small-molecule anti
      inflammatory agents for the treatment of asthma. This patent analysis was
      performed using multiple search engines including SciFinder and Free Patents
      Online. EXPERT OPINION: This review highlights that significant research is still
      directed towards the development of novel anti-inflammatory agents for the
      treatment of asthma. Current standard-of-care therapies are given topically to
      the lung via an inhaled dose, which the authors believe can offer significant
      advantages in terms of efficacy and therapeutic index, compared with an oral
      dose. Several of the patents reviewed disclose preferred compounds and data that
      suggest an inhaled approach is being specifically pursued. The patents reviewed
      target a wide range of inflammatory pathways, although none have yet delivered an
      approved novel medicine for asthma; this gives an indication of both the
      opportunity and challenge involved in such an endeavor.

PMID- 25972123
TI  - The Impact of Education and Socioeconomic and Occupational Conditions on Self
      Perceived and Mental Health Inequalities Among Immigrants and Native Workers in
      Spain.
AB  - There is limited evidence on the influence of social determinants on the self
      perceived and mental health of immigrants settled at least 8 years in Spain. The
      aim of this study was to examine differences between workers related to migrant
      status, self-perceived and mental health, and to assess their relationship to
      occupational conditions, educational level and occupational social class,
      stratified by sex. Using data from the Spanish National Health Survey of 2011/12,
      we computed prevalence, odds ratios and explicative fractions. Mental (OR 2.02;
      CI 1.39-2.93) and self-perceived health (OR 2.64; CI 1.77-3.93) were poorer for
      immigrant women compared to natives. Occupational social class variable
      contributes 25% to self-perceived health OR in immigrant women. Settled immigrant
      women workers are a vulnerable group in Spain.

PMID- 25972124
TI  - Dioxanone-fused dienes enable highly endo-selective intramolecular Diels-Alder
      reactions.
AB  - Intramolecular Diels-Alder reactions of dioxanone-fused (Z,Z)-dienes, available
      in a stereoselective manner from the corresponding alcohols are described. These
      dienes exhibited high reactivity and high levels of endo selectivity, giving
      functionalized trans-fused bicyclic compounds. 

PMID- 25972121
TI  - Scheme of Ischaemia-triggered Agents during Brain Infarct Evolution in a Rat
      Model of Permanent Focal Ischaemia.
AB  - The impact of therapeutic intervention in stroke depends on its appropriate
      timing during infarct evolution. We have studied markers of brain tissue damage
      initiated by permanent occlusion of the middle cerebral artery (MCAO) at three
      time points during which the infarct spread (1, 3 and 6 h). Based on Evans Blue
      extravasation and immunohistochemical detection of neurons, we confirmed
      continuous disruption of blood-brain barrier and loss of neurons in the ischaemic
      hemisphere that peaked at the sixth hour, especially in the core. Glutamate
      content started to rise dramatically in the entire hemisphere during the first 3
      h; the highest level was determined in the core 6 h after MCAO (141 % increase).
      Moreover, the enzyme antioxidant defence grew by about 42 % since the first hour
      in the ipsilateral penumbra. Enzymes of the apoptotic pathway as well as
      mitochondrial enzyme release were detected since the third hour of MCAO in the
      ischaemic hemisphere; all achieved their maxima in the penumbra during both time
      periods (except cytochrome C). In conclusion, the preserved integrity of
      mitochondrial membrane and incompletely developed process of apoptosis may
      contribute to the better therapeutic outcome after ischaemic attack; however, a
      whole brain response should not be omitted. 

PMID- 25972125
TI  - Glycosyltransferases involved in the synthesis of MUC-associated metastasis
      promoting selectin ligands.
AB  - The sialyl Lewis a and x (sLe(a/x)) antigens frequently displayed on the surface
      of tumor cells are involved in metastasis. Their synthesis has been attributed to
      altered expression of selective glycosyltransferases. Identification of these
      glycosyltransferases and the glycoproteins that carry these carbohydrate antigens
      should help advance our understanding of selectin-mediated cancer metastasis. In
      this study, quantitative real-time polymerase chain reaction analysis coupled
      with in situ proximity ligation assay and small interference RNA treatment shows
      involvement of beta3galactosyltransferase-V in the synthesis of MUC16-associated
      sLe(a) in H292 cells. Also, alpha3fucosyltransferase-V, which is absent in BEAS
      2B human immortalized bronchial epithelial cells and A549 lung carcinoma cells,
      participates in the synthesis of MUC1-associated sLe(x) in CFT1 human
      immortalized bronchial epithelial cells and H292 lung carcinoma cells. Neither
      selectin ligand is found on MUC1 in BEAS-2B and A549 cells. Knockdown of either
      enzyme suppresses migration, and selectin tethering and rolling properties of
      H292 cells under dynamic flow as determined by wound healing and parallel plate
      flow chamber assays, respectively. These results provide insights into how the
      synthesis of mucin-associated selectin ligands and the metastatic properties of
      cancer cells can be regulated by selective glycosyltransferases that work on
      mucins. They may help develop novel anticancer drugs. 

PMID- 25972126
TI  - The effect of Ramadan fasting on quiescent systemic lupus erythematosus (SLE)
      patients' disease activity, health quality of life and lipid profile: a pilot
      study.
AB  - SLE is a common autoimmune disease with considerable morbidity. Ramadan fasting
      is a religious custom Muslims regularly practice. We aimed to evaluate the effect
      of Ramadan fasting on SLE patients' disease activity, health quality of life and
      lipid profile. We conducted this case control study as a pilot study in 40
      quiescent SLE patients, 21 cases who decided to fast and 19 controls who decided
      not to have Ramadan fasting between August and November 2009 in lupus unit of
      Rheumatology Research Center in Tehran University of Medical Sciences, Iran. They
      were assessed for SLE Disease Activity Index, lipid profile and quality of life
      with Short-Form 36 (SF-36) Health Survey, 1 day before Ramadan, the day after and
      3 months after Ramadan fasting. After 24.1 +/- 5.4 (mean +/- SD) days of fasting,
      anti-ds DNA increased for 0.34 +/- 0.41 mmol/dL in cases versus 0.07 +/- 0.31 in
      controls (P = 0.026). Likewise C3 increased more dramatically in cases (16.8 +/-
      17.5 vs. 2.3 +/- 13.2 mg/dL, P = 0.006). Three months after fasting, anti-ds DNA
      was still increased 0.28 +/- 0.46 mmol/dL in cases while a 0.02 +/- 0.43 mmol/dL
      drop in controls was detected (P = 0.04). On the contrary, C3 returned to
      baseline. These changes were not accompanied with significant changes in disease
      activity and health quality of life. Ramadan fasting had no effect on lipid
      profile except for delayed total cholesterol decrease in cases in comparison with
      controls (16.4 +/- 29.4 decrease vs. 4.6 +/- 23.9 mg/dL decrease, P = 0.018).
      Ramadan fasting probably has no detrimental effect on SLE patients' disease
      activity and their quality of life in the quiescent phase of disease. 

PMID- 25972127
TI  - Person-centredness in direct care workers caring for residents with dementia:
      Effects of a psycho-educational intervention.
AB  - This study assessed the effects of a psycho-educational intervention on direct
      care workers' person-centredness during morning care to residents with dementia.
      A controlled pretest-posttest study was conducted in four aged-care facilities
      with 56 direct care workers (female, mean age 44.72 +/- 9.02). Two experimental
      facilities received a psycho-educational intervention comprising person-centred
      care competences and stress management skills; control facilities received an
      education-only intervention, without stress support. In total, 112 video-recorded
      morning care sessions were coded using the Global Behaviour Scale. Both groups
      reported significantly higher scores on eight of 11 items of the Global Behaviour
      Scale and on the Global Behaviour Scale total score at posttest (F=10.59;
      p=0.02). Global Behaviour Scale total score improvements were higher for the
      experimental group, with values close to significance (F=3.90; p=0.054). The
      findings suggest that a psycho-educational intervention may increase care
      workers' person-centredness. Further research is needed to explore the long-term
      sustainability and extent of its benefits on workers and residents.

PMID- 25972128
TI  - Increasing enjoyable activities to treat depression in nursing home residents
      with dementia: A pilot study.
AB  - This pilot study aimed to assess the feasibility and acceptability of a
      behavioral activities intervention (BE-ACTIV) in Australian nursing homes. BE
      ACTIV was developed by researchers at the University of Louisville, USA, to
      improve mood and quality of life (QOL) in nursing home residents with mild to
      moderate dementia. An eight-week trial was conducted and 10 residents with mild
      to moderate dementia received the BE-ACTIV intervention while eight residents
      received a Walking and Talking intervention. Measures of depression (GDS-12R) and
      QOL (QOL-AD-NH) were administered prior to and following the interventions.
      Qualitative feedback indicated residents benefited from BE-ACTIV, evident by
      improved mood, although no statistically significant treatment effect was found.
      Moreover, the intervention was found to be feasible and acceptable to Australian
      nursing home staff and our findings highlight the importance of individualizing
      activities for people with dementia, of which 1:1 staff attention was a key
      component.

PMID- 25972129
TI  - Systemic complications of status epilepticus--An update.
AB  - Systemic complications occur at every stage of status epilepticus, involve every
      organ system, and may worsen outcome. Initially, there is a massive catecholamine
      release and hyperadrenergic state that may result in neurocardiogenic, pulmonary,
      and, sometimes, musculoskeletal or renal injury. Further medical complications
      accompany the various treatments used to abort the seizures including the use of
      nonanesthetic antiseizure drugs and high-dose anesthetic infusions. Later,
      sequelae of prolonged immobility and critical illness occur and add to the
      cumulative morbidity of these patients. Clinicians should follow a protocol to
      guide screening for early markers of systemic injury, complications of specific
      pharmacologic and adjunctive treatments, and periodic surveillance for
      complications related to prolonged immobility. This article is part of a Special
      Issue entitled "Status Epilepticus". 

PMID- 25972130
TI  - Quality of life and sense of coherence in young people and adults with
      uncomplicated epilepsy: A longitudinal study.
AB  - OBJECTIVES: The aim of the study was, in a ten-year follow-up, to describe and
      explore potential changes in quality of life and sense of coherence in relation
      to gender differences among persons with epilepsy in the transition from
      adolescence to adulthood. MATERIALS AND METHODS: A longitudinal study of sense of
      coherence (SOC) and quality of life with repeated measurement design (1999, 2004,
      and 2009) was conducted in a population of persons (n = 69) who were aged 13-22
      years in 1999 and 23-33 years in 2009. The Quality-of-Life Index (QLI) and the
      Sense of Coherence (SOC) scale were used. RESULTS: There was a significant
      decrease (p <= 0.001) in seizures compared with the 2004 results, mainly among
      the women (p = 0.003). When comparing the total QLI scores, no significant
      differences were found between the three data collections and there were no
      differences in total scores between men and women. There was a decrease in the
      SOC total score over the 10-year period study. Total SOC was significantly higher
      among those being 30-33 years old compared to those being 23-29 years old (p =
      0.014) and among those having a driving license (p = 0.029) compared to those not
      having a driving license. CONCLUSIONS: Both quality of life and sense of
      coherence are important for maintaining health and well-being. Promoting health
      and well-being requires effective high-quality multidisciplinary person-centered
      care.

PMID- 25972131
TI  - Response to "Vascular Precursor Epilepsy - Old wine in new skins?".

PMID- 25972132
TI  - What do epileptologists recommend about discontinuing antiepileptic drugs for a
      second time in children?
AB  - OBJECTIVE: There is a broad consensus that antiepileptic drugs (AEDs) may be
      withdrawn after two years of seizure freedom for most children with epilepsy. If
      seizures recur and are, again, completely controlled with AEDs, little is known
      about discontinuing a second time. We surveyed American and Canadian pediatric
      epileptologists to understand their current practice. METHODS: In 2014, a survey
      was sent via e-mail to 193 pediatric epileptologists to learn about AED
      discontinuation practices in children. The survey asked direct questions about
      practice and posed five "real-life" cases where the decision to discontinue might
      be difficult. Participants were identified through membership lists of several US
      and Canadian epilepsy organizations. RESULTS: There were 94 (49%) completed
      surveys. Sixty-three participants had >= 10 years in practice ("more
      experienced": mean 23 +/- 9 years), and 31 had < 10 years ("less experienced":
      mean 6 +/- 2 ). Overall, 62% recommended AED discontinuation for the first time
      after 2-3 years of seizure freedom, and 61% recommended discontinuation for the
      second time after 2-3 years. Fifty-six percent of "more experienced" clinicians
      required a longer seizure-free period prior to a second discontinuation (p <
      0.001) compared with 26% of "less experienced" clinicians (p = ns). Overall, most
      participants suggested an AED taper duration of 2-6 months for the first and
      second attempts, 52% and 68%, respectively. Both groups wean AEDs more slowly
      during the second attempt (p < 0.001). There was only 40-60% agreement among
      participants to discontinue AEDs in four of the cases. CONCLUSION: Nearly half
      (46%) of pediatric epileptologists require a longer seizure-free period the
      second time they attempt to discontinue AEDs compared with the first attempt and
      wean down AEDs somewhat more slowly. Although a variety of factors influence
      decision-making, there was a high level of disagreement to discontinue AEDs a
      second time in "real-life" cases.

PMID- 25972133
TI  - Validation of palpatory methods for evaluating anatomical bone landmarks of the
      cervical spine: a systematic review.
AB  - OBJECTIVE: The aim of this study was to systematically review the literature for
      validity of palpatory procedures for evaluating anatomical bone landmarks in the
      cervical spine. METHODS: A systematic search of electronic databases identified
      observational studies assessing validity and/or accuracy regarding evaluation of
      anatomical bone landmarks of cervical spine palpatory procedures. The databases
      used in the search included the US National Library of Medicine of the National
      Institutes of Health (MEDLINE/PubMed), the Regional Library of Medicine (Bireme),
      the Scientific Electronic Library Online (SciELO), the Physiotherapy Evidence
      Database (PEDro), the Latin American and Caribbean Health Sciences Literature
      database (LILACS), the Cochrane Library, and Coordination of Personnel
      Improvement of Higher Education (CAPES/Brazil). Data were extracted by a primary
      reviewer, and 2 independent reviewers used a critical appraisal tool to estimate
      the quality of the retrieved studies. The results were synthesized qualitatively
      within the Quality Assessment of Diagnostic Accuracy Studies criteria. After
      completing the synthesis and scoring, the reviewers applied classifications such
      as "low," "fair," and "good." RESULTS: The initial search yielded 69860 articles.
      After selection criteria were applied, 5 studies satisfied the eligibility
      criteria. Three studies verified the validity of the manual palpatory procedure,
      and 2 studies correlated the findings of the palpatory procedures with other
      measured results. According to Quality Assessment of Diagnostic Accuracy Studies
      criteria, 3 studies presented good methodological quality, and 2 presented fair
      methodological quality. Studies demonstrated an accuracy range from 51% to 87.8%.
      CONCLUSION: There are few studies that evaluate the validity of manual palpatory
      procedures for examining boney landmarks of the cervical spine. The 5 that were
      found showed fair to good methodological quality. However, we note that there may
      be poor external validity due to the sampling heterogeneity of these studies.

PMID- 25972134
TI  - Exotic topological density waves in cold atomic Rydberg-dressed fermions.
AB  - Versatile controllability of interactions in ultracold atomic and molecular gases
      has now reached an era where quantum correlations and unconventional many-body
      phases can be studied with no corresponding analogues in solid-state systems.
      Recent experiments in Rydberg atomic gases have achieved exquisite control over
      non-local interactions, allowing novel quantum phases unreachable with the usual
      local interactions in atomic systems. Here we study Rydberg-dressed atomic
      fermions in a three-dimensional optical lattice predicting the existence of
      hitherto unheard-of exotic mixed topological density wave phases. By varying the
      spatial range of the non-local interaction, we find various chiral density waves
      with spontaneous time-reversal symmetry breaking, whose quasiparticles form three
      dimensional quantum Hall and Weyl semimetal states. Remarkably, certain density
      waves even exhibit mixed topologies beyond the existing topological
      classification. Our results suggest gapless fermionic states could exhibit far
      richer topology than previously expected. 

PMID- 25972135
TI  - The nutcracker syndrome. Morphology and clinical aspects of the important
      vascular variations: a systematic study of 112 cases.
AB  - Nutcracker syndrome (NCS) is the name given to entrapment of the left renal vein
      (LRV) between the aorta and superior mesenteric artery (SMA). The aim of the
      study was to review current research and clarify the most common clinical image
      of the syndrome. A systematic review of PubMed and EBSCO databases was performed.
      Articles included in the study had to meet the following criteria: publication
      between 1980 and 2014, a detailed report on patient symptoms and laboratory test
      results, medical imaging confirmation of LRV entrapment diagnosis. Fifty-five
      publications which met the inclusion criteria provided the final database
      containing 112 cases. The male-female distribution was equal, the mean age on
      diagnosis for the whole group was 26.47+/-13.77years. Diagnosis was made earlier
      in males (23.59+/-13.09) than females (29.34+/-13.93). The following frequency of
      symptoms was noted: 78.57% for haematuria, 38.39% for left flank pain, 35.71% for
      varicocele in males, 30.36% for proteinuria and 13.39% for anaemia. NCS diagnosis
      was made earlier if proteinuria occurred as one of the symptoms (P<0.001). Anemia
      occurred more often in older patients (P=0.0128). NCS was diagnosed in younger
      age in patients with varicocele (P=0.037). Although NCS is not a common
      diagnosis, it should be taken into consideration, particularly in hematuria of
      unknown origin and varicocele. 

PMID- 25972136
TI  - Analysis of the effects of micronized purified flavonoid fraction versus placebo
      on symptoms and quality of life in patients suffering from chronic venous
      disease: from a prospective randomized trial.
AB  - AIM: The aim was to investigate the effect of micronized purified flavonoid
      fraction (MPFF; Daflon(r) 500 mg, Laboratoires Servier, France) versus placebo,
      on pain and quality of life (QoL) in patients with symptomatic chronic venous
      disease (CVD). METHODS: A large randomized, double-blind, placebo-controlled,
      parallel-group study was conducted to evaluate treatment effects on vesperal
      oedema using water displacement volumetry (WDV). Other criteria were leg
      pain?heaviness assessed by Visual Analog Scale (VAS) and Quality Of Life
      Questionnaire (CIVIQ-20). Study treatments were administered once a day for 4
      months. The tolerance to the study treatments was assessed based on spontaneously
      reported adverse events, coded using the MedDRA dictionary. The present post-hoc
      analysis focuses on the subgroup of symptomatic patients having a baseline VAS>4
      cm. RESULTS: The main study included 1137 patients classified C3 or C4 according
      to CEAP classification, with 592 in the symptomatic subgroup: 296 randomized to
      MPFF and 296 to placebo. Patient demographics and medical history were well
      balanced at baseline. The main study was inconclusive on WDV for methodological
      reasons. In the symptomatic subgroup, MPFF treatment was associated with a
      greater reduction in VAS score than on placebo treatment (between-group
      difference =-0.5 cm; P=0.031) and greater improvement in CIVIQ score (between
      group difference =3.1%; P=0.040). CONCLUSION: A 4-month treatment with MPFF
      significantly reduced leg pain/heaviness and improved QOL when compared to
      placebo and was well tolerated.

PMID- 25972137
TI  - Incidence of severe coronary stenosis in asymptomatic patients with peripheral
      arterial disease scheduled for major vascular surgery.
AB  - BACKGROUND: Peripheral arterial disease (PAD) has the risk equivalent of coronary
      heart disease. The biochemical parameters associated with functionally
      significant coronary artery stenosis were investigated in asymptomatic patients
      with PAD who were scheduled for major vascular intervention. METHODS: A total of
      50 PAD patients asymptomatic for coronary heart disease were examined using
      coronary computed tomography angiography (CTA). A stress myocardial CT perfusion
      (CTP) test was performed in patients who exhibited coronary stenosis >40%. In
      patients with stress-induced perfusion defects, the severity of stenosis was
      assessed using invasive coronary angiography including fractional flow reserve
      assessment. The CT findings were correlated with both classical and more recently
      developed parameters of atherosclerosis. RESULTS: According to the combined CT
      examination (CTA and stress CT perfusion), 36% of patients exhibited significant
      coronary stenosis. Stress-induced hypoperfusion was observed in 95.7% of severe
      stenotic lesions. After adjustment for confounders, the level of high-sensitivity
      troponin I was associated with severe coronary stenosis (OR 1.260 [95% CI 1.054
      to 1.505]). Other biochemical parameters did not correlate with coronary
      stenosis. The annual mortality rate was 4%. CONCLUSIONS: The results of the
      present study confirm a significant diagnostic contribution of a complex cardiac
      CT examination in patients scheduled for major vascular surgery. A high
      prevalence of asymptomatic coronary heart disease was observed in this particular
      patient group. High-sensitivity measurements of troponin I correlated with the
      extent of the coronary stenosis.

PMID- 25972138
TI  - Flow-mediated dilation benefits of mesoglycan in peripheral artery disease.
AB  - AIM: Mesoglycan, composed of natural glycosaminoglycans, is used for treatment in
      arterial and venous disease for its benefits on endothelial glicocalix. Little is
      known about mesoglycan impact on endothelial blood flow regulation. We sought to
      evaluate the effects of mesoglycan intermittently added to back-ground treatments
      on impairment of endothelial function in peripheral arterial disease (PAD)
      patients. METHODS: We studied the effects of a 2+2 months oral treatment with 50
      mg b.i.d. of mesoglycan, intervalled by 2 months without mesoglycan, in 540 PAD
      patients on four occasions (visit 1: baseline, visit 2: 2 months, visit 3: 4
      months and visit 4: 6 months). At these time visits we assessed brachial artery
      endothelial-dependent flow-mediated dilation (FMD), together with femoral intima
      medial thickness (IMT), and walking distance (WD). RESULTS: There were
      significant changes in FMD (1.88%, CI 95%: 1.13, 2.63; P<0.001), IMT (-0.05 mm,
      CI 95%: -0.07,-0.02; P<0.001) and WD (38,9%, CI 95% 33.2, 44.8; P<0.001). The
      positive effects and benefit were maintained during the two-months interval
      without mesoglycan treatment. Significant changes in FMD were observed in a
      number of patient groups, stratified for risk factors (aging, sex, smoke,
      diabetes, dyslipidemia, hypertension). CONCLUSION: Two months cycles with
      mesoglycan improved endothelial function in PAD patients, with a parallel
      reduction of atherosclerotic damage and amelioration of clinical condition.

PMID- 25972139
TI  - Patient-reported Chiari malformation type I symptoms and diagnostic experiences:
      a report from the national Conquer Chiari Patient Registry database.
AB  - Chiari malformation (CM) is a condition in which cerebellar tonsillar ectopia may
      manifest with various clinical presentations. This study reports from the only
      national, online patient registry available, the symptoms, comorbid
      neurocognitive and psychological conditions, and diagnostic experiences of
      patients living with CM type I (CM I). The current research is one component of a
      large investigation designed to collect information from individuals with CM
      through the online Conquer Chiari Patient Registry questionnaire. Analyses
      included descriptive statistics to study body system impact and patient
      diagnostic experiences. Participants were 768 individuals with CM I and were
      predominantly female (86.8 %) and Caucasian (93.8 %) with an average age of 35
      years. Pain was the most frequently reported symptom (76.69 %) experienced prior
      to diagnosis with headaches implicated most often (73.44 %). Neurocognitive
      comorbidities included memory difficulties (43.88 %) and aphasia (43.75 %) and
      psychological disorders such as depression (31.77 %) and anxiety disorders (19.92
      %) were reported. Average time to diagnosis from first physician visit to
      diagnosis was 3.43 years, and only 8.46 % of patients had previous awareness of
      CM. CM I diagnosis was found incidentally for 24.87 % of participants. Common
      misdiagnoses were classified as psychological (19.26 %) and neurological (19.26
      %). Fear was the most frequent emotion elicited at the time of correct diagnosis
      (42.19 %). CM I can be a challenging condition for patients and physicians,
      during both the search for diagnosis and management of symptoms. Patient and
      physician education about CM I may permit early intervention and the prevention
      of further deterioration and patient suffering.

PMID- 25972140
TI  - Stem cell-based therapies for intracerebral hemorrhage in animal model: a meta
      analysis.
AB  - Stem cell to be a new intervention for treating intracerebral hemorrhage (ICH)
      might benefit humans. Therefore, we collected animal studies to find the effect
      of this innovative treatment. In July 2014, we searched Medline (from 1950),
      Embase (from 1980), China Biology Medicine disk (from 1978) for studies on stem
      cells used for treating experimental ICH in animal models that reported
      neurobehavioral and structural outcome. We evaluated the quality of these studies
      and used a weighted mean difference random affects model for the meta-analysis.
      We have collected 30 studies from 650 publications identified through systematic
      review describing the effects of 5 different type of stem cells on 12 different
      neurobehavioral scales with 1101 rodents or monkeys. Although there is lack of
      uniformity of the evaluation methods, these researches showed consistent
      improvements both in neurobehavioral function and structural outcomes. Besides,
      the quality of these studies needs to be raised. In conclusion, stem cells hold
      extensive potential in treating ICH, which should be further evaluated with more
      evidence-based, high-quality animal studies. 

PMID- 25972141
TI  - Alien hand syndrome and paroxystic dystonia after right posterior cerebral artery
      territory infarction.

PMID- 25972142
TI  - Caries prevalence and enamel defects in 5- and 10-year-old children with cleft
      lip and/or palate: A case-control study.
AB  - OBJECTIVE: To determine the prevalence of dental caries and enamel defects in 5-
      and 10-year-old Swedish children with cleft lip and/or palate (CL(P)) in
      comparison to non-cleft controls. MATERIALS AND METHODS: The study group
      consisted of 139 children with CL(P) (80 subjects aged 5 years and 59 aged 10
      years) and 313 age-matched non-cleft controls. All children were examined by one
      of two calibrated examiners. Caries was scored according to the International
      Caries Detection and Assessment System (ICDAS-II) and enamel defects as presence
      and frequency of hypoplasia and hypomineralization. RESULTS: The caries
      prevalence among the 5-year-old CL(P) children and the non-cleft controls was 36%
      and 18%, respectively (p < 0.05). The CL(P) children had higher caries frequency
      (initial and cavitated lesions) in the primary dentition than their controls (1.2
      vs 0.9; p < 0.05). A significantly higher prevalence of enamel defects was found
      in CL(P) children of both age groups and anterior permanent teeth were most
      commonly affected. CONCLUSIONS: Preschool children with cleft lip and/or palate
      seem to have more caries in the primary dentition than age-matched non-cleft
      controls. Enamel defects were more common in CL(P) children in both age groups.

PMID- 25972144
TI  - Direct Conversion of Cord Blood CD34+ Cells Into Neural Stem Cells by OCT4.
AB  - : Cellular reprogramming or conversion is a promising strategy to generate
      desired stem cell types from somatic cells. Neural stem cells (NSCs) have the
      potential to regenerate central nervous system tissue and repair damage in
      response to injury. However, NSCs are difficult to isolate from human tissues and
      expand in sufficient quantities for therapy. Here, we report a method to generate
      neural stem cells from cord blood CD34-positive cells by ectopic expression of
      OCT4 in a feeder-free system. The induced cells (iNSCs) show a characteristic NSC
      like morphology and can be expanded in vitro for more than 20 passages. In
      addition, the iNSCs are positive for neural stem cell-specific markers such as
      Nestin and Musashi-1 and are similar in gene expression patterns to a human
      neural stem cell line. The iNSCs express distinct transcriptional factors for
      forebrain, hindbrain, and spinal cord regions. Upon differentiation, the iNSCs
      are able to commit into multilineage mature neural cells. Following in vivo
      introduction into NOD/SCID mice, iNSCs can survive and differentiate in the mouse
      brain 3 months post-transplantation. Alternatively, we were also able to derive
      iNSCs with an episomal vector expressing OCT4. Our results suggest a novel,
      efficient approach to generate neural precursor cells that can be potentially
      used in drug discovery or regenerative medicine for neurological disease and
      injury. SIGNIFICANCE: This study describes a novel method to generate expandable
      induced neural stem cells from human cord blood cells in a feeder-free system by
      a single factor, OCT4. The data are promising for future applications that
      require the generation of large amounts of autologous neural stem cells in
      disease modeling and regenerative medicine.

PMID- 25972145
TI  - In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic
      Neurons.
AB  - : Huntington's disease (HD) results from a CAG repeat expansion in the gene
      encoding the huntingtin protein. This inherited disorder is characterized by
      progressive neurodegeneration. In particular, HD progression involves the loss of
      striatal projection neurons. The limited availability of reliable sources of
      human striatal projection neurons currently hampers our understanding of HD
      mechanisms and hinders the development of novel HD treatments. In this paper, we
      described two- and three-step methods for differentiating human neural progenitor
      cells toward striatal projection neurons. In the two-step differentiation
      protocol, 90%, 54%, and 6% of MAP2-positive cells were immunopositive for GABA,
      calbindin (CALB1), and DARPP-32/PPP1R1B, respectively. In the three-step
      differentiation protocol, 96%, 84%, and 21% of MAP2-positive cells were
      immunopositive for GABA, calbindin, and DARPP-32/PPP1R1B, respectively. In line
      with a striatal projection neuron phenotype, cells differentiated with our
      protocols displayed significantly increased expression of MAP2, CALB1, DARPP
      32/PPP1R1B, ARPP21, and CTIP2. Application of glutamate receptor agonists induced
      calcium influx; accordingly, the cells also expressed various ionotropic
      glutamate receptor subunits. Differentiated cells also released GABA on
      stimulation. We suggest that our three-step differentiation protocol presents a
      reliable and simplified method for the generation of striatal projection neurons,
      yielding a critical resource for neuronal physiology and neurodegenerative
      disorder studies. SIGNIFICANCE: The earliest changes in the neurodegenerative
      disorder Huntington's disease affect a specific type of brain neurons, the so
      called medium spiny neurons of the striatum. In this study, two protocols were
      developed for the differentiation of neural progenitor cells into striatal medium
      spiny neurons, and the differentiated neurons were extensively characterized. The
      data indicate that the three-step differentiation protocol presents a reliable
      and simplified method for the generation of striatal medium spiny neurons. The
      generated striatal medium spiny neurons could represent a critical resource for
      the study of neurodegenerative disorders, a model system for drug discovery, and
      a step toward cell-based regeneration therapies.

PMID- 25972146
TI  - Development of a Monitoring Method for Nonlabeled Human Pluripotent Stem Cell
      Growth by Time-Lapse Image Analysis.
AB  - : Cell growth is an important criterion for determining healthy cell conditions.
      When somatic cells or cancer cells are dissociated into single cells for
      passaging, the cell numbers can be counted at each passage, providing information
      on cell growth as an indicator of the health conditions of these cells. In the
      case of human pluripotent stem cells (hPSCs), because the cells are usually
      dissociated into cell clumps of ~50-100 cells for passaging, cell counting is
      time-consuming. In the present study, using a time-lapse imaging system, we
      developed a method to determine the growth of hPSCs from nonlabeled live cell
      phase-contrast images without damaging these cells. Next, the hPSC colony areas
      and number of nuclei were determined and used to derive equations to calculate
      the cell number in hPSC colonies, which were assessed on time-lapse images
      acquired using a culture observation system. The relationships between the colony
      areas and nuclei numbers were linear, although the equation coefficients were
      dependent on the cell line used, colony size, colony morphology, and culture
      conditions. When the culture conditions became improper, the change in cell
      growth conditions could be detected by analysis of the phase-contrast images.
      This method provided real-time information on colony growth and cell growth rates
      without using treatments that can damage cells and could be useful for basic
      research on hPSCs and cell processing for hPSC-based therapy. SIGNIFICANCE: This
      is the first study to use a noninvasive method using images to systemically
      determine the growth of human pluripotent stem cells (hPSCs) without damaging or
      wasting cells. This method would be useful for quality control during cell
      culture of clinical hPSCs.

PMID- 25972147
TI  - Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic
      Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor.
AB  - : Because adipose-derived stem cells (ASCs) are usually expanded to acquire large
      numbers of cells for therapeutic applications, it is important to increase the
      production yield and regenerative potential during expansion. Therefore, a
      tremendous need exists for alternative ASC stimuli during cultivation to increase
      the proliferation and adipogenic differentiation of ASCs. The present study
      primarily investigated the involvement of megestrol acetate (MA), a progesterone
      analog, in the stimulation of ASCs, and identifies the target receptors
      underlying stimulation. Mitogenic and adipogenic effects of MA were investigated
      in vitro, and pharmacological inhibition and small interfering (si) RNA
      techniques were used to identify the molecular mechanisms involved in the MA
      induced stimulation of ASCs. MA significantly increased the proliferation,
      migration, and adipogenic differentiation of ASCs in a dose-dependent manner.
      Glucocorticoid receptor (GR) is highly expressed compared with other nuclear
      receptors in ASCs, and this receptor is phosphorylated after MA treatment. MA
      also upregulated genes downstream of GR in ASCs, including ANGPTL4, DUSP1,
      ERRF11, FKBP5, GLUL, and TSC22D3. RU486, a pharmacological inhibitor of GR, and
      transfection of siGR significantly attenuated MA-induced proliferation,
      migration, and adipogenic differentiation of ASCs. Although the adipogenic
      differentiation potential of MA was inferior to that of dexamethasone, MA had
      mitogenic effects in ASCs. Collectively, these results indicate that MA increases
      the proliferation, migration, and adipogenic differentiation of ASCs via GR
      phosphorylation. SIGNIFICANCE: Magestrol acetate (MA) increases the
      proliferation, migration, and adipogenic differentiation of adipose-derived stem
      cells (ASCs) via glucocorticoid receptor phosphorylation. Therefore, MA can be
      applied to increase the production yield during expansion and can be used to
      facilitate adipogenic differentiation of ASCs.

PMID- 25972148
TI  - Doppler Ultrasound and Transient Elastography in Liver Transplant Patients for
      Noninvasive Evaluation of Liver Fibrosis in Comparison with Histology: A
      Prospective Observational Study.
AB  - BACKGROUND AND AIM: Accurate quantification of progressive liver disease is
      essential for therapeutic decisions and follow-up for patients who underwent
      liver transplantation. To evaluate the quality of noninvasive assessment of liver
      fibrosis in these patients, we compared Doppler ultrasound of the hepatic blood
      vessels as well as transient elastography (TE, FibroScan((r))) with liver biopsy
      following transplantation. METHODS: We performed Doppler ultrasound of the
      hepatic veins, hepatic artery, and portal vein as well as a TE in 48 patients who
      underwent liver transplantation 12 months ago. Hepatic venous flow was evaluated
      by determination of the resistance index (HVRI) of the right hepatic vein.
      Doppler and TE results were compared with histopathologic workup of a 12-month
      protocol liver biopsy after transplantation. RESULTS: HVRI showed a high
      reliability in predicting liver fibrosis stage FII or higher (AUROC of 0.99 +/-
      0.001 for FII or higher, the HVRI < 1.05 with a sensitivity and specificity of
      100 and 91.43 %) compared to histopathologic workup (Desmet's score) and was
      comparable to TE analysis. Both HVRI and TE differed significantly in no or
      minimal fibrosis versus FII or higher (p < 0.001). In contrast, portal vein and
      hepatic artery did not show significant changes in blood flow in our study
      population. CONCLUSIONS: Hepatic vein flow resistance index is a valuable tool in
      noninvasive evaluation of liver fibrosis in liver transplantation follow-up
      predicting FII or higher and might help reducing the number of protocol biopsies
      needed.

PMID- 25972149
TI  - Tregs: A Therapeutic Target for the Treatment of Portal Fibrosis?

PMID- 25972150
TI  - Gastrointestinal and Hepatic Manifestations of Ebola Virus Infection.
AB  - AIM: Although Ebola virus infection (EVI) clinically presents with common,
      prominent, gastroenterologic manifestations, this subject has not been previously
      reviewed. This work critically and comprehensively reviews this subject. METHODS:
      This study is a comprehensive literature review generated by computerized search
      of literature, supplemented by review of monographs and textbooks in pathology,
      gastroenterology, infectious diseases, and virology. RESULTS: Common
      gastrointestinal manifestations include diarrhea-70 %, nausea and vomiting-60 %,
      and abdominal pain-45 %. The diarrhea and nausea and vomiting frequently produce
      profound, life-threatening hypovolemia requiring intravenous administration of
      crystalloid solutions, and frequently produce electrolyte disorders requiring
      electrolyte supplementation. Although gastrointestinal hemorrhage was commonly
      reported in early epidemics, its frequency has decreased to 10 % with prevention
      of disseminated intravascular coagulation. Hyperamylasemia is commonly reported,
      but the frequency of pancreatitis is unknown. The mean serum AST and ALT levels
      are each about 200/UL, with an unusual pattern for viral hepatitis of AST > ALT.
      The serum alkaline phosphatase averages about 160 IU/L, whereas the total
      bilirubin averages about 0.8 mg/dL. Risks of contracting infection during
      endoscopy performed on infected patients are unknown, but may be significant, as
      indicated by hundreds of healthcare workers contracting EVI during epidemics
      before instituting strict infectious control measures and anecdotal evidence of
      one endoscopist contracting EVI from performing endoscopy on an infected patient.
      CONCLUSIONS: Physicians must be vigilant for gastroenterologic manifestations of
      EVI for appropriate diagnosis and therapy. This work should stimulate
      clinicopathologic studies to improve the current understanding of the
      gastroenterologic pathophysiology. Endoscopy is currently not standardly
      recommended to evaluate diarrhea, nausea and vomiting, or abdominal pain
      associated with EVI due to potential risks, but may be considered for endoscopic
      therapy for active, life-threatening, GI hemorrhage.

PMID- 25972151
TI  - Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating
      Mitochondrial Pathway by Increasing Reactive Oxygen Species.
AB  - BACKGROUND: Hesperetin, has been shown to exert biological activities on various
      types of human cancers. However, few related studies on gastric cancer are
      available. AIM: In this study, we sought to investigate the effect of hesperetin
      on gastric cancer and clarify its specific mechanism. MATERIALS AND METHODS: Cell
      Counting Kit-8, 2',7'-dichlorofluorescin diacetate, JC-1, Hoechst 33258 staining,
      and western bolt were used to detect cell viability, levels of intracellular
      reactive oxygen species (ROS), changes in mitochondrial membrane potential (?psi
      m), cell apoptosis, and expressions of mitochondrial pathway proteins,
      respectively. Meanwhile, xenograft tumor models in nude mice were made to
      evaluate the effect of hesperetin on gastric cancer in vivo. RESULTS: Compared
      with the control group, the proliferation of gastric cancer cells in hesperetin
      groups was significantly inhibited (P < 0.05), and dose- and time-dependent
      effects were observed. Pretreatment with H2O2 (1 mM) or N-acetyl-L-cysteine (5
      mM) enhanced or attenuated the hesperetin-induced inhibition of cell viability (P
      < 0.05). Percentages of apoptotic cells, levels of intracellular ROS, and ?psi m
      varied with the dose and treatment time of hesperetin (P < 0.05), and hesperetin
      caused an increase in the levels of AIF, Apaf-1, Cyt C, caspase-3, caspase-9, and
      Bax and a decrease in Bcl-2 levels (P < 0.05). Meanwhile, hesperetin
      significantly inhibited the growth of xenograft tumors (P < 0.05). CONCLUSION:
      Our study suggests that hesperetin could inhibit the proliferation and induce the
      apoptosis of gastric cancer cells via activating the mitochondrial pathway by
      increasing the ROS.

PMID- 25972152
TI  - Role of Dopamine and D2 Dopamine Receptor in the Pathogenesis of Inflammatory
      Bowel Disease.
AB  - BACKGROUND: VEGF-induced vascular permeability and blood vessels remodeling are
      key features of inflammatory bowel disease (IBD) pathogenesis. Dopamine through
      D2 receptor (D2R) inhibits VEGF/VPF-mediated vascular permeability and
      angiogenesis in tumor models. In this study, we tested the hypothesis that
      pathogenesis of IBD is characterized by the disturbance of dopaminergic system
      and D2R activity. METHODS: IL-10 knockout (KO) mice and rats with iodoacetamide
      induced ulcerative colitis (UC) were treated intragastrically with D2R agonists
      quinpirole (1 mg/100 g) or cabergoline (1 or 5 ug/100 g). Macroscopic,
      histologic, and clinical features of IBD, colonic vascular permeability, and
      angiogenesis were examined. RESULTS: Although colonic D2R protein increased,
      levels of tyrosine hydroxylase and dopamine transporter DAT decreased in both
      models of IBD. Treatment with quinpirole decreased the size of colonic lesions in
      rats with iodoacetamide-induced UC (p < 0.01) and reduced colon wet weight in IL
      10 KO mice (p < 0.05). Quinpirole decreased colonic vascular permeability (p <
      0.001) via downregulation of c-Src and Akt phosphorylation. Cabergoline (5 ug/100
      g) reduced vascular permeability but did not affect angiogenesis and improved
      signs of iodoacetamide-induced UC in rats (p < 0.05). CONCLUSIONS: Treatment with
      D2R agonists decreased the severity of UC in two animal models, in part, by
      attenuation of enhanced vascular permeability and prevention of excessive
      vascular leakage. Hence, the impairment dopaminergic system seems to be a feature
      of IBD pathogenesis.

PMID- 25972153
TI  - Persistent Reactive Thrombocytosis May Increase the Risk of Coronary Artery
      Disease Among Inflammatory Bowel Disease Patients.
AB  - BACKGROUND: IBD patients are at increased risk of coronary artery disease in the
      absence of traditional risk factors. However, the disease-related risk factors
      remain poorly understood although increased inflammation seems to increase
      cardiovascular disease risk in IBD. Thrombocytes are involved in the pathogenesis
      of coronary artery disease, and a subset of IBD patients have reactive
      thrombocytosis. AIM: The aim of our study was to investigate the effect of
      persistent reactive thrombocytosis on the development of coronary artery disease
      in IBD. METHODS: We evaluated a retrospective cohort of 2525 IBD patients who
      were evaluated at the Henry Ford hospital from 2000 to 2004. We performed a case
      control study comparing patients with persistent thrombocytosis and patients
      without persistent thrombocytosis. Cases (n = 36) and controls (n = 72) were
      matched for age and gender. Coronary artery disease incidence was compared
      between the two groups. RESULTS: Cases (n = 36) and controls (n = 72) were
      matched for age and gender. Cases and controls were similar in age at onset of
      IBD (41.5 vs. 35.5, p value 0.11) and smoking status (33.3 vs. 27.8%, p value
      0.66). Persistent thrombocytosis was less common among Caucasian patients (44.44
      vs. 62.5%, p value 0.09) and more common in patients who had exposure to steroids
      during the study follow-up period. Coronary artery disease occurred in 13 (36.1%)
      patients with persistent thrombocytosis compared to only seven (9.7%) patients in
      the control group. CONCLUSIONS: Persistent reactive thrombocytosis among IBD
      patients is associated with increased risk of coronary artery disease. Further
      studies should characterize the clinical and molecular associations of this
      phenomenon and determine appropriate therapeutic measures.

PMID- 25972155
TI  - Intranasal administration of butorphanol benefits old patients undergoing H
      uvulopalatopharyngoplasty: a randomized trial.
AB  - BACKGROUND: To evaluate intranasal administration of butorphanol on postoperative
      pain and early postoperative cognitive dysfunction in old patients undergoing H
      uvulopalatopharyngoplasty (H-UPPP). METHODS: A total of 260 male patients (65 to
      77 years old) with obstructive sleep apnea hypopnea syndrome and scheduled for H
      UPPP were divided randomly to receive intranasal butorphanol, intravenous
      butorphanol, intranasal fentanyl, or intravenous saline (controls). The
      definition of preemptive analgesia is that the tested drugs are given before
      anesthesia induction. Visual analog scale (VAS) and Bruggrmann comfort scale
      (BCS) scores were recorded at postoperative 1, 6, 12, 18, 24, 36, and 48 h.
      Postoperative cognitive dysfunction (POCD) was evaluated by Mini-Mental State
      Examination (MMSE) scores assessed one day before, and 1, 3, and 7 days
      postsurgery. RESULTS: Compared with control group, those given preemptive
      analgesia required significantly less sufentanil during surgery, had less pain at
      postoperative 6-12 h; those given butorphanol experienced less nausea and
      vomiting, less pain at postoperative 6-24 h, and less POCD. Compared with
      patients given fentanyl, those given butorphanol required significantly less
      postoperative fentanyl, had less pain at postoperative 18-24 h, less nausea and
      vomiting, and less POCD. Compared with patients given intravenous butorphanol,
      those who received butorphanol by nasal route required significantly less
      postoperative fentanyl, had less pain at 36 and 48 h, and less POCD. CONCLUSION:
      Intranasal administration of butorphanol is safe and effective, reducing
      postoperative usage of analgesics and the incidence of POCD in old patients
      undergoing H-UPPP. TRIAL REGISTRATION: ChiCTR-TRC-14004121.

PMID- 25972154
TI  - Zingiberaceae extracts for pain: a systematic review and meta-analysis.
AB  - BACKGROUND: Members of the family Zingiberaceae including turmeric, ginger,
      Javanese ginger, and galangal have been used for centuries in traditional
      medicine. Preclinical studies of Zingiberaceae extracts have shown analgesic
      properties. This study aims to systematically review and meta-analyze whether
      extracts from Zingiberaceae are clinically effective hypoalgesic agents. METHODS:
      Literature was screened from electronic databases using the key words
      Zingiberaceae AND pain OR visual analogue score (VAS) to identify randomized
      trials. From this search, 18 studies were identified, and of these, 8 randomized,
      double-blinded, placebo-controlled trials were found that measured pain by VAS
      for inclusion in the meta-analysis. RESULTS: Findings indicated significant
      efficacy of Zingiberaceae extracts in reducing subjective chronic pain (SMD -
      0.67; 95 % CI - 1.13 to - 0.21; P = 0.004). A linear dose-effect relationship was
      apparent between studies (R(2) = 0.71). All studies included in the systematic
      review reported a good safety profile for extracts, without the renal risks
      associated with non-steroidal anti-inflammatory drugs, and with similar
      effectiveness. CONCLUSION: Our findings indicated that Zingiberaceae extracts are
      clinically effective hypoalgesic agents and the available data show a better
      safety profile than non-steroidal anti-inflammatory drugs. However, both non
      steroidal anti-inflammatory drugs and Zingiberaceae have been associated with a
      heightened bleeding risk, and there have been no comparator trials of this risk.
      Further clinical studies are recommended to identify the most effective type of
      Zingiberaceae extract and rigorously compare safety, including bleeding risk.

PMID- 25972156
TI  - The Effectiveness of Anti-leukotriene Agents in Patients with COPD: A Systemic
      Review and Meta-analysis.
AB  - BACKGROUND: Anti-leukotriene (anti-LT) agents have been not yet established for
      effectiveness in patients with chronic obstructive pulmonary disease (COPD). We
      performed a systematic review and meta-analysis to assess whether anti-LT agents
      have the responsiveness for COPD patients. METHODS: MEDLINE, EMBASE, Cochrane
      Central Register, and Korea Med were searched for relevant clinical trials to
      review. RESULTS: Seven studies involving 342 patients were finally analyzed.
      Pooled estimation from three randomized controlled studies did not demonstrate
      that anti-LT agents increased forced expiratory volume in 1 s [overall effect:
      0.09 L, 95 % confidence interval (CI) -0.04 to 0.21; P = 0.17; I (2)  = 41.0 %]
      or forced vital capacity (overall effect: 0.04 L, 95 % CI -0.04 to 0.11; P =
      0.64; I (2) = 0.0 %). As for inflammatory markers, anti-LT agents did not affect
      the level of myeloperoxidase (standardized mean difference, -0.15; 95 % CI -0.65
      to 0.36) or LTB4 (standardized mean difference, -0.41; 95 % CI -0.96 to 0.13).
      They reduced the frequency of dyspnea [relative risk (RR) 0.43; 95 % CI 0.29 to
      0.64] and sputum (RR 0.37; 95 % CI 0.22 to 0.63), based on overall estimation
      from two non-randomized studies. However, our review revealed that there are few
      well-designed, randomized controlled studies with large sample sizes and long
      treatment durations. CONCLUSION: Although symptomatic improvements were
      demonstrated in some studies, there is a lack of evidence to support the
      therapeutic efficacy of anti-LT agents in patients with COPD. Further large
      scale, long-term studies are needed to identify predictive factors for COPD
      patients who may benefit from anti-LT agents.

PMID- 25972159
TI  - MicroRNA-155-deficient dendritic cells cause less severe GVHD through reduced
      migration and defective inflammasome activation.
AB  - The successful treatment of acute leukemias with allogeneic hematopoietic cell
      transplantation (allo-HCT) is limited by acute graft-versus-host disease (GVHD).
      Because microRNA-155 (miR-155) regulates activation of the innate immune system,
      we aimed to determine its function in dendritic cells (DCs) during GVHD in an
      experimental model. We observed that miR-155 deficiency of the recipient led to
      improved survival, reduced serum levels of proinflammatory cytokines, and lower
      GVHD histopathology scores. In addition, miR-155(-/-) bone marrow chimeric mice
      receiving allo-HCT and miR-155(-/-) DCs showed that miR-155 deficiency in the DC
      compartment was responsible for protection from GVHD. Activated miR-155(-/-) DCs
      displayed lower expression of various purinergic receptors and impaired migration
      toward adenosine triphosphate (ATP). Microarray analysis of
      lipopolysaccharide/ATP-stimulated miR-155(-/-) DCs revealed mitogen-activated
      protein kinase pathway dysregulation and reduced inflammasome-associated gene
      expression. Consistent with this gene expression data, we observed reduced ERK
      activation, caspase-1 cleavage, and IL-1beta production in miR-155(-/-) DCs. The
      connection between miR-155 and inflammasome activation was supported by the fact
      that Nlrp3/miR-155 double-knockout allo-HCT recipient mice had no increased
      protection from GVHD compared with Nlrp3(-/-) recipients. This study indicates
      that during GVHD, miR-155 promotes DC migration toward sites of ATP release
      accompanied by inflammasome activation. Inhibiting proinflammatory miR-155 by
      antagomir treatment could help reduce this complication of allo-HCT. 

PMID- 25972157
TI  - Hypermorphic mutation of phospholipase C, gamma2 acquired in ibrutinib-resistant
      CLL confers BTK independency upon B-cell receptor activation.
AB  - Ibrutinib has significantly improved the outcome of patients with relapsed
      chronic lymphocytic leukemia (CLL). Recent reports attribute ibrutinib resistance
      to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the
      target of ibrutinib, as well as the immediate downstream effector phospholipase
      C, gamma2 (PLCG2). Although the C481S mutation found in BTK has been shown to
      disable ibrutinib's capacity to irreversibly bind this primary target, the
      detailed mechanisms of mutations in PLCG2 have yet to be established. Herein, we
      characterize the enhanced signaling competence, BTK independence, and surface
      immunoglobulin dependence of the PLCG2 mutation at R665W, which has been
      documented in ibrutinib-resistant CLL. Our data demonstrate that this missense
      alteration elicits BTK-independent activation after B-cell receptor engagement,
      implying the formation of a novel BTK-bypass pathway. Consistent with previous
      results, PLCG2(R665W) confers hypermorphic induction of downstream signaling
      events. Our studies reveal that proximal kinases SYK and LYN are critical for the
      activation of mutant PLCG2 and that therapeutics targeting SYK and LYN can combat
      molecular resistance in cell line models and primary CLL cells from ibrutinib
      resistant patients. Altogether, our results engender a molecular understanding of
      the identified aberration at PLCG2 and explore its functional dependency on BTK,
      SYK, and LYN, suggesting alternative strategies to combat acquired ibrutinib
      resistance. 

PMID- 25972158
TI  - A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab,
      and cyclosporine (TT4).
AB  - Promising reports of combination immunosuppression with high-dose dexamethasone
      and rituximab for the treatment of primary immune thrombocytopenia (ITP) have
      recently emerged. They suggest a potential to further optimize the efficacy of
      therapy. We investigate the use of a novel combination of conventional therapies
      in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively
      enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and
      tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5
      to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for
      days 7, 14, 21, and 28. There were no therapy-related serious adverse side
      effects, 6-month response rate was 60%, and treatment was well tolerated.
      Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and
      24 months. This study highlights the possibility of achieving an enduring
      remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au
      (#ANZCTRN12611000015943). 

PMID- 25972161
TI  - Expansion and State-Dependent Variability along Sensory Processing Streams.

PMID- 25972160
TI  - Inducing iron deficiency improves erythropoiesis and photosensitivity in
      congenital erythropoietic porphyria.
AB  - Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of
      heme synthesis characterized by reduced activity of uroporphyrinogen III synthase
      and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting
      in ineffective erythropoiesis and devastating skin photosensitivity. Management
      of the disease primarily consists of supportive measures. Increased activity of 5
      aminolevulinate synthase 2 (ALAS2) has been shown to adversely modify the disease
      phenotype. Herein, we present a patient with CEP who demonstrated a remarkable
      improvement in disease manifestations in the setting of iron deficiency.
      Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2
      activity and subsequent porphyrin production, we treated the patient with off
      label use of deferasirox to maintain iron deficiency, with successful results. We
      confirmed the physiology of her response with marrow culture studies. 

PMID- 25972162
TI  - MU-Opioid Receptor-Mediated Inhibition of Intercalated Neurons and Effect on
      Synaptic Transmission to the Central Amygdala.
AB  - The amygdala is a key region for the processing of information underlying fear,
      anxiety, and fear extinction. Within the local neuronal networks of the amygdala,
      a population of inhibitory, intercalated neurons (ITCs) modulates the flow of
      information among various nuclei of amygdala, including the basal nucleus (BA)
      and the centromedial nucleus (CeM) of the amygdala. These ITCs have been shown to
      be important during fear extinction and are target of a variety of
      neurotransmitters and neuropeptides. Here we provide evidence that the activation
      of MU-opioid receptors (MORs) by the specific agonist DAMGO ([D-Ala2,N-Me
      Phe4,Gly5-ol]-Enkephalin) hyperpolarizes medially located ITCs (mITCs) in acute
      brain slices of mice. Moreover, we use whole-cell patch-clamp recordings in
      combination with local electrical stimulation or glutamate uncaging to analyze
      the effect of MOR activation on local microcircuits. We show that the GABAergic
      transmission between mITCs and CeM neurons is attenuated by DAMGO, whereas the
      glutamatergic transmission on CeM neurons and mITCs is unaffected. Furthermore,
      MOR activation induced by theta burst stimulation in BA suppresses plastic
      changes of feedforward inhibitory transmission onto CeM neurons as revealed by
      the MOR antagonist CTAP d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2. In summary, the
      mITCs constitute a target for the opioid system, and therefore, the activation of
      MOR in ITCs might play a central role in the modulation of the information
      processing between the basolateral complex of the amygdala and central nuclei of
      the amygdala. 

PMID- 25972163
TI  - Consolidation of Associative and Item Memory Is Related to Post-Encoding
      Functional Connectivity between the Ventral Tegmental Area and Different Medial
      Temporal Lobe Subregions during an Unrelated Task.
AB  - It is well established that the hippocampus and perirhinal cortex (PrC) encode
      associative and item representations, respectively. However, less is known about
      how item and associative memories are consolidated. We used high-resolution fMRI
      in humans to measure how functional connectivity between these distinct medial
      temporal lobe regions with the ventral tegmental area (VTA) after a paired
      associate encoding task is related to both immediate and 24 h item and
      associative memory performance. We found that the strength of post-encoding
      functional connectivity between the VTA and CA1 selectively correlated with long
      term associative memory, despite subjects actively engaging in an unrelated task
      during this period. Conversely, VTA-PrC functional connectivity during the same
      period correlated with long-term item memory. Critically, connectivity between
      VTA and these MTL regions were only related to memory tested at a 24 h delay,
      implicating midbrain connectivity in the consolidation of distinct forms of
      memory. 

PMID- 25972164
TI  - Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1
      Gene Transcription, in Brain Ischemia and in Ischemic Brain Preconditioning, by
      Epigenetic Mechanism.
AB  - The Na(+)-Ca(2+) exchanger 1 (NCX1) is reduced in stroke by the RE1-silencing
      transcription factor (REST), whereas it is increased in ischemic brain
      preconditioning (PC) by hypoxia-inducible factor 1 (HIF-1). Because ncx1 brain
      promoter (ncx1-Br) has five putative consensus sequences, named Sp1A-E, for the
      specificity protein (Sp) family of transcription factors (Sp1-4), we investigated
      the role of this family in regulating ncx1 transcription in rat cortical neurons.
      Here we found that Sp1 is a transcriptional activator, whereas Sp3 is a
      transcriptional repressor of ncx1, and that both bind ncx1-Br in a sequence
      specific manner, modulating ncx1 transcription through the Sp1 sites C-E.
      Furthermore, by transient middle cerebral artery occlusion (tMCAO) in rats, the
      transcriptional repressors Sp3 and REST colocalized with the two histone
      deacetylases (HDACs) HDAC1 and HDAC2 on the ncx1-Br, with a consequent
      hypoacetylation. Contrarily, in PC+tMCAO the transcriptional activators Sp1 and
      HIF-1 colocalized with histone acetyltransferase p300 on ncx1-Br with a
      consequent hyperacetylation. In addition, in neurons silenced with siRNA of NCX1
      and subjected to oxygen and glucose deprivation (OGD) (3 h) plus reoxygenation
      (RX) (24 h), the neuroprotection of Class I HDAC inhibitor MS-275 was
      counteracted, whereas in neurons overexpressing NCX1 and subjected to ischemic
      preconditioning (PC+OGD/RX), the neurotoxic effect of p300 inhibitor C646 was
      prevented. Collectively, these results demonstrate that NCX1 expression is
      regulated by the Sp3/REST/HDAC1/HDAC2 complex in tMCAO and by the Sp1/HIF-1/p300
      complex in PC+tMCAO and that epigenetic intervention, by modulating the
      acetylation of ncx1-Br, may be a strategy for the development of innovative
      therapeutic intervention in stroke. 

PMID- 25972165
TI  - Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites
      for Pharmacological Intervention in Neuronal Disease Models.
AB  - The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA
      receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed
      benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction
      regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and
      anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia,
      post-traumatic stress disorder, and autism to cardiovascular disorders and breast
      cancer. Understanding protein interactions required for NOS1AP function,
      therefore, has broad implications for numerous diseases. Here we show that the
      interaction of NOS1AP with nNOS differs radically from the classical PDZ docking
      assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by
      multiple methods. In contrast, full-length NOS1AP forms an unusually stable
      interaction with nNOS. We mapped the discrepancy between full-length and C
      terminal PDZ motif to a novel internal region we call the ExF motif. The C
      terminal PDZ motif, although neither sufficient nor necessary for binding,
      nevertheless promotes the stability of the complex. It therefore potentially
      affects signal transduction and suggests that functional interaction of nNOS with
      NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic
      pathways can be regulated, in cortical neuron and organotypic hippocampal slice
      cultures from rat, either by the previously described PDZ ligand TAT-GESV or by
      the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ
      residues as long as the ExF motif is intact and not mutated. This previously
      unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide
      distinct opportunities for pharmacological intervention in NOS1AP-dependent
      signaling and excitotoxicity. 

PMID- 25972166
TI  - Neural mechanisms of placebo anxiolysis.
AB  - The beneficial effects of placebo treatments on fear and anxiety (placebo
      anxiolysis) are well known from clinical practice, and there is strong evidence
      indicating a contribution of treatment expectations to the efficacy of anxiolytic
      drugs. Although clinically highly relevant, the neural mechanisms underlying
      placebo anxiolysis are poorly understood. In two studies in humans, we tested
      whether the administration of an inactive treatment along with verbal suggestions
      of anxiolysis can attenuate experimentally induced states of phasic fear and/or
      sustained anxiety. Phasic fear is the response to a well defined threat and
      includes attentional focusing on the source of threat and concomitant phasic
      increases of autonomic arousal, whereas in sustained states of anxiety potential
      and unclear danger requires vigilant scanning of the environment and elevated
      tonic arousal levels. Our placebo manipulation consistently reduced vigilance
      measured in terms of undifferentiated reactivity to salient cues (indexed by
      subjective ratings, skin conductance responses and EEG event-related potentials)
      and tonic arousal [indexed by cue-unrelated skin conductance levels and enhanced
      EEG alpha (8-12 Hz) activity], indicating a downregulation of sustained anxiety
      rather than phasic fear. We also observed a placebo-dependent sustained increase
      of frontal midline EEG theta (4-7 Hz) power and frontoposterior theta coupling,
      suggesting the recruitment of frontally based cognitive control functions. Our
      results thus support the crucial role of treatment expectations in placebo
      anxiolysis and provide insight into the underlying neural mechanisms. 

PMID- 25972167
TI  - Toward an autonomous brain machine interface: integrating sensorimotor reward
      modulation and reinforcement learning.
AB  - For decades, neurophysiologists have worked on elucidating the function of the
      cortical sensorimotor control system from the standpoint of kinematics or
      dynamics. Recently, computational neuroscientists have developed models that can
      emulate changes seen in the primary motor cortex during learning. However, these
      simulations rely on the existence of a reward-like signal in the primary
      sensorimotor cortex. Reward modulation of the primary sensorimotor cortex has yet
      to be characterized at the level of neural units. Here we demonstrate that single
      units/multiunits and local field potentials in the primary motor (M1) cortex of
      nonhuman primates (Macaca radiata) are modulated by reward expectation during
      reaching movements and that this modulation is present even while subjects
      passively view cursor motions that are predictive of either reward or nonreward.
      After establishing this reward modulation, we set out to determine whether we
      could correctly classify rewarding versus nonrewarding trials, on a moment-to
      moment basis. This reward information could then be used in collaboration with
      reinforcement learning principles toward an autonomous brain-machine interface.
      The autonomous brain-machine interface would use M1 for both decoding movement
      intention and extraction of reward expectation information as evaluative
      feedback, which would then update the decoding algorithm as necessary. In the
      work presented here, we show that this, in theory, is possible. 

PMID- 25972168
TI  - Heterogeneity and Bipotency of Astroglial-Like Cerebellar Progenitors along the
      Interneuron and Glial Lineages.
AB  - Cerebellar GABAergic interneurons in mouse comprise multiple subsets of
      morphologically and neurochemically distinct phenotypes located at strategic
      nodes of cerebellar local circuits. These cells are produced by common
      progenitors deriving from the ventricular epithelium during embryogenesis and
      from the prospective white matter (PWM) during postnatal development. However, it
      is not clear whether these progenitors are also shared by other cerebellar
      lineages and whether germinative sites different from the PWM originate
      inhibitory interneurons. Indeed, the postnatal cerebellum hosts another germinal
      site along the Purkinje cell layer (PCL), in which Bergmann glia are generated up
      to first the postnatal weeks, which was proposed to be neurogenic. Both PCL and
      PWM comprise precursors displaying traits of juvenile astroglia and neural stem
      cell markers. First, we examine the proliferative and fate potential of these
      niches, showing that different proliferative dynamics regulate progenitor
      amplification at these sites. In addition, PCL and PWM differ in the generated
      progeny. GABAergic interneurons are produced exclusively by PWM astroglial-like
      progenitors, whereas PCL precursors produce only astrocytes. Finally, through in
      vitro, ex vivo, and in vivo clonal analyses we provide evidence that the
      postnatal PWM hosts a bipotent progenitor that gives rise to both interneurons
      and white matter astrocytes. 

PMID- 25972169
TI  - Predictions of Visual Content across Eye Movements and Their Modulation by
      Inferred Information.
AB  - The brain is proposed to operate through probabilistic inference, testing and
      refining predictions about the world. Here, we search for neural activity
      compatible with the violation of active predictions, learned from the
      contingencies between actions and the consequent changes in sensory input. We
      focused on vision, where eye movements produce stimuli shifts that could, in
      principle, be predicted. We compared, in humans, error signals to saccade
      contingent changes of veridical and inferred inputs by contrasting the
      electroencephalographic activity after saccades to a stimulus presented inside or
      outside the blind spot. We observed early (<250 ms) and late (>250 ms) error
      signals after stimulus change, indicating the violation of sensory and
      associative predictions, respectively. Remarkably, the late response was
      diminished for blind-spot trials. These results indicate that predictive signals
      occur across multiple levels of the visual hierarchy, based on generative models
      that differentiate between signals that originate from the outside world and
      those that are inferred. 

PMID- 25972170
TI  - NKCC1 Activation Is Required for Myelinated Sensory Neurons Regeneration through
      JNK-Dependent Pathway.
AB  - After peripheral nerve injury, axons are able to regenerate, although specific
      sensory reinnervation and functional recovery are usually worse for large
      myelinated than for small sensory axons. The mechanisms that mediate the
      regeneration of different sensory neuron subpopulations are poorly known. The
      Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) is particularly relevant in setting the
      intracellular chloride concentration. After axotomy, increased NKCC1
      phosphorylation has been reported to be important for neurite outgrowth of
      sensory neurons; however, the mechanisms underlying its effects are still
      unknown. In the present study we used in vitro and in vivo models to assess the
      differential effects of blocking NKCC1 activity on the regeneration of different
      types of dorsal root ganglia (DRGs) neurons after sciatic nerve injury in the
      rat. We observed that blocking NKCC1 activity by bumetanide administration
      induces a selective effect on neurite outgrowth and regeneration of myelinated
      fibers without affecting unmyelinated DRG neurons. To further study the mechanism
      underlying NKCC1 effects, we also assessed the changes in mitogen-activated
      protein kinase (MAPK) signaling under NKCC1 modulation. The inhibition of NKCC1
      activity in vitro and in vivo modified pJNK1/2/3 expression in DRG neurons.
      Together, our study identifies a mechanism selectively contributing to myelinated
      axon regeneration, and point out the role of Cl(-) modulation in DRG neuron
      regeneration and in the activation of MAPKs, particularly those belonging to the
      JNK family. 

PMID- 25972171
TI  - Mapping the macaque superior temporal sulcus: functional delineation of vergence
      and version eye-movement-related activity.
AB  - It is currently thought that the primate oculomotor system has evolved distinct
      but interrelated subsystems to generate different types of visually guided eye
      movements (e.g., saccades/smooth pursuit/vergence). Although progress has been
      made in elucidating the neural basis of these movement types, no study to date
      has investigated all three movement types on a large scale and within the same
      animals. Here, we used fMRI in rhesus macaque monkeys to map the superior
      temporal sulcus (STS) for BOLD modulation associated with visually guided eye
      movements. Further, we ascertained whether modulation in a given area was
      movement type specific and, if not, the modulation each movement type elicited
      relative to the others (i.e., dominance). Our results show that multiple areas
      within STS modulate during all movement types studied, including the middle
      temporal, medial superior temporal, fundus of the superior temporal, lower
      superior temporal, and dorsal posterior inferotemporal areas. Our results also
      reveal an area in dorsomedial STS that is modulated almost exclusively by
      vergence movements. In contrast, we found that ventrolateral STS is driven
      preferentially during versional movements. These results illuminate an STS
      network involved in processes associated with multiple eye movement types,
      illustrate unique patterns of modulation within said network as a function of
      movement type, and provide evidence for a vergence-specific area within
      dorsomedial STS. We conclude that producing categorically different eye movement
      types requires access to a common STS network and that individual network nodes
      are recruited differentially based upon the type of movement generated. 

PMID- 25972172
TI  - Neurons in the Primate Medial Basal Forebrain Signal Combined Information about
      Reward Uncertainty, Value, and Punishment Anticipation.
AB  - It has been suggested that the basal forebrain (BF) exerts strong influences on
      the formation of memory and behavior. However, what information is used for the
      memory-behavior formation is unclear. We found that a population of neurons in
      the medial BF (medial septum and diagonal band of Broca) of macaque monkeys
      encodes a unique combination of information: reward uncertainty, expected reward
      value, anticipation of punishment, and unexpected reward and punishment. The
      results were obtained while the monkeys were expecting (often with uncertainty) a
      rewarding or punishing outcome during a Pavlovian procedure, or unexpectedly
      received an outcome outside the procedure. In vivo anterograde tracing using
      manganese-enhanced MRI suggested that the major recipient of these signals is the
      intermediate hippocampal formation. Based on these findings, we hypothesize that
      the medial BF identifies various contexts and outcomes that are critical for
      memory processing in the hippocampal formation. 

PMID- 25972173
TI  - Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term
      Depression.
AB  - Postsynaptic AMPA-type glutamate receptors (AMPARs) are among the major
      determinants of synaptic strength and can be trafficked into and out of synapses.
      Neuronal activity regulates AMPAR trafficking during synaptic plasticity to
      induce long-term changes in synaptic strength, including long-term potentiation
      (LTP) and long-term depression (LTD). Rab family GTPases regulate most membrane
      trafficking in eukaryotic cells; particularly, Rab11 and its effectors are
      implicated in mediating postsynaptic AMPAR insertion during LTP. To explore the
      synaptic function of Rab11Fip5, a neuronal Rab11 effector and a candidate autism
      spectrum disorder gene, we performed shRNA-mediated knock-down and genetic knock
      out (KO) studies. Surprisingly, we observed robust shRNA-induced synaptic
      phenotypes that were rescued by a Rab11Fip5 cDNA but that were nevertheless not
      observed in conditional KO neurons. Both in cultured neurons and acute slices, KO
      of Rab11Fip5 had no significant effect on basic parameters of synaptic
      transmission, indicating that Rab11Fip5 is not required for fundamental synaptic
      operations, such as neurotransmitter release or postsynaptic AMPAR insertion. KO
      of Rab11Fip5 did, however, abolish hippocampal LTD as measured both in acute
      slices or using a chemical LTD protocol in cultured neurons but did not affect
      hippocampal LTP. The Rab11Fip5 KO mice performed normally in several behavioral
      tasks, including fear conditioning, but showed enhanced contextual fear
      extinction. These are the first findings to suggest a requirement for Rab11Fip5,
      and presumably Rab11, during LTD. 

PMID- 25972174
TI  - The Order and Place of Neuronal Differentiation Establish the Topography of
      Sensory Projections and the Entry Points within the Hindbrain.
AB  - Establishing topographical maps of the external world is an important but still
      poorly understood feature of the vertebrate sensory system. To study the
      selective innervation of hindbrain regions by sensory afferents in the zebrafish
      embryo, we mapped the fine-grained topographical representation of sensory
      projections at the central level by specific photoconversion of sensory neurons.
      Sensory ganglia located anteriorly project more medially than do ganglia located
      posteriorly, and this relates to the order of sensory ganglion differentiation.
      By single-plane illumination microscopy (SPIM) in vivo imaging, we show that (1)
      the sequence of arrival of cranial ganglion inputs predicts the topography of
      central projections, and (2) delaminated neuroblasts differentiate in close
      contact with the neural tube, and they never loose contact with the neural
      ectoderm. Afferent entrance points are established by plasma membrane
      interactions between primary differentiated peripheral sensory neurons and neural
      tube border cells with the cooperation of neural crest cells. These first
      contacts remain during ensuing morphological growth to establish pioneer axons.
      Neural crest cells and repulsive slit1/robo2 signals then guide axons from later
      differentiating neurons toward the neural tube. Thus, this study proposes a new
      model by which the topographical representation of cranial sensory ganglia is
      established by entrance order, with the entry points determined by cell contact
      between the sensory ganglion cell bodies and the hindbrain. 

PMID- 25972175
TI  - Synapsin determines memory strength after punishment- and relief-learning.
AB  - Adverse life events can induce two kinds of memory with opposite valence,
      dependent on timing: "negative" memories for stimuli preceding them and
      "positive" memories for stimuli experienced at the moment of "relief." Such
      punishment memory and relief memory are found in insects, rats, and man. For
      example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock
      training ("forward conditioning" of the odor), whereas after shock-odor training
      ("backward conditioning" of the odor) they approach it. Do these timing-dependent
      associative processes share molecular determinants? We focus on the role of
      Synapsin, a conserved presynaptic phosphoprotein regulating the balance between
      the reserve pool and the readily releasable pool of synaptic vesicles. We find
      that a lack of Synapsin leaves task-relevant sensory and motor faculties
      unaffected. In contrast, both punishment memory and relief memory scores are
      reduced. These defects reflect a true lessening of associative memory strength,
      as distortions in nonassociative processing (e.g., susceptibility to handling,
      adaptation, habituation, sensitization), discrimination ability, and changes in
      the time course of coincidence detection can be ruled out as alternative
      explanations. Reductions in punishment- and relief-memory strength are also
      observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by
      acutely restoring Synapsin and by locally restoring it in the mushroom bodies of
      mutant flies. Thus, both punishment memory and relief memory require the Synapsin
      protein and in this sense share genetic and molecular determinants. We note that
      corresponding molecular commonalities between punishment memory and relief memory
      in humans would constrain pharmacological attempts to selectively interfere with
      excessive associative punishment memories, e.g., after traumatic experiences. 

PMID- 25972176
TI  - Increased prefrontal cortex neurogranin enhances plasticity and extinction
      learning.
AB  - Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed
      as a possible therapeutic tool to enhance extinction, a process that is impaired
      in post-traumatic stress disorder, schizophrenia, and addiction. To test this
      hypothesis, we generated transgenic mice that overexpress neurogranin (a
      calmodulin-binding protein that facilitates long-term potentiation) in the PFC.
      Neurogranin overexpression in the PFC enhanced long-term potentiation and
      increased the rates of extinction learning of both fear conditioning and sucrose
      self-administration. Our results indicate that elevated neurogranin function
      within the PFC can enhance local plasticity and increase the rate of extinction
      learning across different behavioral tasks. Thus, neurogranin can provide a
      molecular link between enhanced plasticity and enhanced extinction. 

PMID- 25972177
TI  - Aging after noise exposure: acceleration of cochlear synaptopathy in "recovered"
      ears.
AB  - Cochlear synaptic loss, rather than hair cell death, is the earliest sign of
      damage in both noise- and age-related hearing impairment (Kujawa and Liberman,
      2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types
      of noise exposure: one producing permanent synaptic damage without hair cell loss
      and another producing neither synaptopathy nor hair cell loss. Adult mice were
      exposed (8-16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ~ 20
      months after exposure. Cochlear function was assessed via distortion product
      otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole
      mounts and plastic sections were studied to quantify hair cells, cochlear
      neurons, and the synapses connecting them. The synaptopathic noise (100 dB)
      caused 35-50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered,
      but synaptic counts and ABR amplitudes at high frequencies were reduced by up to
      ~ 45%. As exposed animals aged, synaptopathy was exacerbated compared with
      controls and spread to lower frequencies. Proportional ganglion cell losses
      followed. Threshold shifts first appeared >1 year after exposure and, by ~ 20
      months, were up to 18 dB greater in the synaptopathic noise group. Outer hair
      cell losses were exacerbated in the same time frame (~ 10% at 32 kHz). In
      contrast, the 91 dB exposure, producing transient threshold shift without acute
      synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as
      animals aged, at least to ~ 1 year after exposure. Therefore, interactions
      between noise and aging may require an acute synaptopathy, but a single
      synaptopathic exposure can accelerate cochlear aging.

PMID- 25972178
TI  - Dysregulated RNA-Induced Silencing Complex (RISC) Assembly within CNS Corresponds
      with Abnormal miRNA Expression during Autoimmune Demyelination.
AB  - MicroRNAs (miRNAs) associate with Argonaute (Ago), GW182, and FXR1 proteins to
      form RNA-induced silencing complexes (RISCs). RISCs represent a critical
      checkpoint in the regulation and bioavailability of miRNAs. Recent studies have
      revealed dysregulation of miRNAs in multiple sclerosis (MS) and its animal model,
      experimental autoimmune encephalomyelitis (EAE); however, the function of RISCs
      in EAE and MS is largely unknown. Here, we examined the expression of Ago, GW182,
      and FXR1 in CNS tissue, oligodendrocytes (OLs), brain-infiltrating T lymphocytes,
      and CD3(+)splenocytes (SCs) of EAE mic, and found that global RISC protein levels
      were significantly dysregulated. Specifically, Ago2 and FXR1 levels were
      decreased in OLs and brain-infiltrating T cells in EAE mice. Accordingly,
      assembly of Ago2/GW182/FXR1 complexes in EAE brain tissues was disrupted, as
      confirmed by immunoprecipitation experiments. In parallel with alterations in
      RISC complex content in OLs, we found downregulation of miRNAs essential for
      differentiation and survival of OLs and myelin synthesis. In brain-infiltrating T
      lymphocytes, aberrant RISC formation contributed to miRNA-dependent
      proinflammatory helper T-cell polarization. In CD3(+) SCs, we found increased
      expression of both Ago2 and FXR1 in EAE compared with nonimmunized mice.
      Therefore, our results demonstrate a gradient in expression of miRNA between
      primary activated T cells in the periphery and polarized CNS-infiltrating T
      cells. These results suggest that, in polarized autoreactive effector T cells,
      miRNA synthesis is inhibited in response to dysregulated RISC assembly, allowing
      these cells to maintain a highly specific proinflammatory program. Therefore, our
      findings may provide a mechanism that leads to miRNA dysregulation in EAE/MS. 

PMID- 25972179
TI  - ApoE4 and Abeta Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation.
AB  - Apolipoprotein E4 (ApoE4) is a major genetic risk factor for several
      neurodegenerative disorders, including Alzheimer's disease (AD). Epigenetic
      dysregulation, including aberrations in histone acetylation, is also associated
      with AD. We show here for the first time that ApoE4 increases nuclear
      translocation of histone deacetylases (HDACs) in human neurons, thereby reducing
      BDNF expression, whereas ApoE3 increases histone 3 acetylation and upregulates
      BDNF expression. Amyloid-beta (Abeta) oligomers, which have been implicated in
      AD, caused effects similar to ApoE4. Blocking low-density lipoprotein receptor
      related protein 1 (LRP-1) receptor with receptor-associated protein (RAP) or LRP
      1 siRNA abolished the ApoE effects. ApoE3 also induced expression of protein
      kinase C epsilon (PKCepsilon) and PKCepsilon retained HDACs in the cytosol.
      PKCepsilon activation and ApoE3 supplementation prevented ApoE4-mediated BDNF
      downregulation. PKCepsilon activation also reversed Abeta oligomer- and ApoE4
      induced nuclear import of HDACs, preventing the loss in BDNF. ApoE4 induced HDAC6
      BDNF promoter IV binding, which reduced BDNF exon IV expression. Nuclear HDAC4
      and HDAC6 were more abundant in the hippocampus of ApoE4 transgenic mice than in
      ApoE3 transgenic mice or wild-type controls. Nuclear translocation of HDA6 was
      also elevated in the hippocampus of AD patients compared with age-matched
      controls. These results provide new insight into the cause of synaptic loss that
      is the most important pathologic correlate of cognitive deficits in AD. 

PMID- 25972180
TI  - The Specification of Cortical Subcerebral Projection Neurons Depends on the
      Direct Repression of TBR1 by CTIP1/BCL11a.
AB  - The acquisition of distinct neuronal fates is fundamental for the function of the
      cerebral cortex. We find that the development of subcerebral projections from
      layer 5 neurons in the mouse neocortex depends on the high levels of expression
      of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons
      that project to subcerebral targets and with SATB2 in those that project to the
      contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as
      a critical step for the acquisition of the subcerebral fate. In contrast, lower
      levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the
      corticothalamic fate. CTIP1 does not appear to play a critical role in the
      acquisition of the callosal projection fate in layer 5. These findings unravel a
      key step in the acquisition of cell fate for closely related corticofugal neurons
      and indicate that differential dosages of transcriptions factors are critical to
      specify different neuronal identities. 

PMID- 25972181
TI  - Task engagement selectively modulates neural correlations in primary auditory
      cortex.
AB  - Noise correlations (r(noise)) between neurons can affect a neural population's
      discrimination capacity, even without changes in mean firing rates of neurons.
      r(noise), the degree to which the response variability of a pair of neurons is
      correlated, has been shown to change with attention with most reports showing a
      reduction in r(noise). However, the effect of reducing r(noise) on sensory
      discrimination depends on many factors, including the tuning similarity, or
      tuning correlation (r(tuning)), between the pair. Theoretically, reducing
      r(noise) should enhance sensory discrimination when the pair exhibits similar
      tuning, but should impair discrimination when tuning is dissimilar. We recorded
      from pairs of neurons in primary auditory cortex (A1) under two conditions: while
      rhesus macaque monkeys (Macaca mulatta) actively performed a threshold amplitude
      modulation (AM) detection task and while they sat passively awake. We report
      that, for pairs with similar AM tuning, average r(noise) in A1 decreases when the
      animal performs the AM detection task compared with when sitting passively. For
      pairs with dissimilar tuning, the average r(noise) did not significantly change
      between conditions. This suggests that attention-related modulation can target
      selective subcircuits to decorrelate noise. These results demonstrate that
      engagement in an auditory task enhances population coding in primary auditory
      cortex by selectively reducing deleterious r(noise) and leaving beneficial
      r(noise) intact.

PMID- 25972182
TI  - Memory of occasional events in rats: individual episodic memory profiles,
      flexibility, and neural substrate.
AB  - In search for the mechanisms underlying complex forms of human memory, such as
      episodic recollection, a primary challenge is to develop adequate animal models
      amenable to neurobiological investigation. Here, we proposed a novel framework
      and paradigm that provides means to quantitatively evaluate the ability of rats
      to form and recollect a combined knowledge of what happened, where it happened,
      and when or in which context it happened (referred to as episodic-like memory)
      after a few specific episodes in situations as close as possible to a paradigm we
      recently developed to study episodic memory in humans. In this task, rats have to
      remember two odor-drink associations (what happened) encountered in distinct
      locations (where it happened) within two different multisensory enriched
      environments (in which context/occasion it happened), each characterized by a
      particular combination of odors and places. By analyzing licking behavior on each
      drinking port, we characterized quantitatively individual recollection profiles
      and showed that rats are able to incidentally form and recollect an accurate,
      long-term integrated episodic-like memory that can last >= 24 d after limited
      exposure to the episodes. Placing rats in a contextually challenging recollection
      situation at recall reveals the ability for flexible use of episodic memory as
      described in humans. We further report that reversible inactivation of the dorsal
      hippocampus during recall disrupts the animal's capacity to recollect the
      complete episodic memory. Cellular imaging of c-Fos and Zif268 brain activation
      reveals that episodic memory recollection recruits a specific, distributed
      network of hippocampal-prefrontal cortex structures that correlates with the
      accuracy of the integrated recollection performance.

PMID- 25972183
TI  - Neurons forming optic glomeruli compute figure-ground discriminations in
      Drosophila.
AB  - Many animals rely on visual figure-ground discrimination to aid in navigation,
      and to draw attention to salient features like conspecifics or predators. Even
      figures that are similar in pattern and luminance to the visual surroundings can
      be distinguished by the optical disparity generated by their relative motion
      against the ground, and yet the neural mechanisms underlying these visual
      discriminations are not well understood. We show in flies that a diverse array of
      figure-ground stimuli containing a motion-defined edge elicit statistically
      similar behavioral responses to one another, and statistically distinct
      behavioral responses from ground motion alone. From studies in larger flies and
      other insect species, we hypothesized that the circuitry of the lobula--one of
      the four, primary neuropiles of the fly optic lobe--performs this visual
      discrimination. Using calcium imaging of input dendrites, we then show that
      information encoded in cells projecting from the lobula to discrete optic
      glomeruli in the central brain group these sets of figure-ground stimuli in a
      homologous manner to the behavior; "figure-like" stimuli are coded similar to one
      another and "ground-like" stimuli are encoded differently. One cell class
      responds to the leading edge of a figure and is suppressed by ground motion. Two
      other classes cluster any figure-like stimuli, including a figure moving opposite
      the ground, distinctly from ground alone. This evidence demonstrates that lobula
      outputs provide a diverse basis set encoding visual features necessary for figure
      detection.

PMID- 25972185
TI  - Activation of Group I and Group II Metabotropic Glutamate Receptors Causes LTD
      and LTP of Electrical Synapses in the Rat Thalamic Reticular Nucleus.
AB  - Compared with the extensive characterization of chemical synaptic plasticity,
      electrical synaptic plasticity remains poorly understood. Electrical synapses are
      strong and prevalent among the GABAergic neurons of the rodent thalamic reticular
      nucleus. Using paired whole-cell recordings, we show that activation of Group I
      metabotropic glutamate receptors (mGluRs) induces long-term depression of
      electrical synapses. Conversely, activation of the Group II mGluR, mGluR3,
      induces long-term potentiation of electrical synapses. By testing downstream
      targets, we show that modifications induced by both mGluR groups converge on the
      same signaling cascade--adenylyl cyclase to cAMP to protein kinase A--but with
      opposing effects. Furthermore, the magnitude of modification is inversely
      correlated to baseline coupling strength. Thus, electrical synapses, like their
      chemical counterparts, undergo both strengthening and weakening forms of
      plasticity, which should play a significant role in thalamocortical function.

PMID- 25972184
TI  - Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long
      Term Potentiation at SC-CA1 Synapses in the Hippocampus.
AB  - Of the eight metabotropic glutamate (mGlu) receptor subtypes, only mGlu7 is
      expressed presynaptically at the Schaffer collateral (SC)-CA1 synapse in the
      hippocampus in adult animals. Coupled with the inhibitory effects of Group III
      mGlu receptor agonists on transmission at this synapse, mGlu7 is thought to be
      the predominant autoreceptor responsible for regulating glutamate release at SC
      terminals. However, the lack of mGlu7-selective pharmacological tools has
      hampered direct testing of this hypothesis. We used a novel, selective mGlu7
      negative allosteric modulator (NAM), ADX71743, and a newly described Group III
      mGlu receptor agonist, LSP4-2022, to elucidate the role of mGlu7 in modulating
      transmission in hippocampal area CA1 in adult C57BL/6J male mice. Interestingly,
      although mGlu7 agonists inhibit SC-CA1 EPSPs, we found no evidence for activation
      of mGlu7 by stimulation of SC-CA1 afferents. However, LSP4-2022 also reduced
      evoked monosynaptic IPSCs in CA1 pyramidal cells and, in contrast to its effect
      on SC-CA1 EPSPs, ADX71743 reversed the ability of high-frequency stimulation of
      SC afferents to reduce IPSC amplitudes. Furthermore, blockade of mGlu7 prevented
      induction of LTP at the SC-CA1 synapse and activation of mGlu7 potentiated
      submaximal LTP. Together, these data suggest that mGlu7 serves as a
      heteroreceptor at inhibitory synapses in area CA1 and that the predominant effect
      of activation of mGlu7 by stimulation of glutamatergic afferents is
      disinhibition, rather than reduced excitatory transmission. Furthermore, this
      mGlu7-mediated disinhibition is required for induction of LTP at the SC-CA1
      synapse, suggesting that mGlu7 could serve as a novel therapeutic target for
      treatment of cognitive disorders. 

PMID- 25972186
TI  - Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are
      Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent
      and Include Lamina I Projection Neurons among Their Postsynaptic Targets.
AB  - The superficial dorsal horn of the spinal cord contains numerous inhibitory
      interneurons, which regulate the transmission of information perceived as touch,
      pain, or itch. Despite the importance of these cells, our understanding of their
      roles in the neuronal circuitry is limited by the difficulty in identifying
      functional populations. One group that has been identified and characterized
      consists of cells in the mouse that express green fluorescent protein (GFP) under
      control of the prion protein (PrP) promoter. Previous reports suggested that PrP
      GFP cells belonged to a single morphological class (central cells), received
      inputs exclusively from unmyelinated primary afferents, and had axons that
      remained in lamina II. However, we recently reported that the PrP-GFP cells
      expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been
      shown that nNOS-expressing cells are more diverse in their morphology and
      synaptic connections. We therefore used a combined electrophysiological,
      pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We
      provide evidence that they are morphologically diverse (corresponding to
      "unclassified" cells) and receive synaptic input from a variety of primary
      afferents, with convergence onto individual cells. We also show that their axons
      project into adjacent laminae and that they target putative projection neurons in
      lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is
      more complex than previously recognized, and suggests that they are likely to
      have several distinct roles in regulating the flow of somatosensory information
      through the dorsal horn. 

PMID- 25972189
TI  - N-Heterocyclic carbene-catalyzed diastereoselective synthesis of beta-lactone
      fused cyclopentanes using homoenolate annulation reaction.
AB  - NHC-catalyzed annulation of enals with 2-enoylpyridines or 2-enoylpyridine N
      oxides leading to the diastereoselective synthesis of beta-lactone-fused
      cyclopentanes is reported. The reaction proceeds via the generation of
      homoenolate equivalent intermediates and tolerates a broad range of functional
      groups. 

PMID- 25972187
TI  - The N-ethylmaleimide-sensitive factor and dysbindin interact to modulate synaptic
      plasticity.
AB  - Dysbindin is a schizophrenia susceptibility factor and subunit of the biogenesis
      of lysosome-related organelles complex 1 (BLOC-1) required for lysosome-related
      organelle biogenesis, and in neurons, synaptic vesicle assembly,
      neurotransmission, and plasticity. Protein networks, or interactomes, downstream
      of dysbindin/BLOC-1 remain partially explored despite their potential to
      illuminate neurodevelopmental disorder mechanisms. Here, we conducted a proteome
      wide search for polypeptides whose cellular content is sensitive to
      dysbindin/BLOC-1 loss of function. We identified components of the vesicle fusion
      machinery as factors downregulated in dysbindin/BLOC-1 deficiency in
      neuroectodermal cells and iPSC-derived human neurons, among them the N
      ethylmaleimide-sensitive factor (NSF). Human dysbindin/BLOC-1 coprecipitates with
      NSF and vice versa, and both proteins colocalized in a Drosophila model synapse.
      To test the hypothesis that NSF and dysbindin/BLOC-1 participate in a pathway
      regulating synaptic function, we examined the role for NSF in dysbindin/BLOC-1
      dependent synaptic homeostatic plasticity in Drosophila. As previously described,
      we found that mutations in dysbindin precluded homeostatic synaptic plasticity
      elicited by acute blockage of postsynaptic receptors. This dysbindin mutant
      phenotype is fully rescued by presynaptic expression of either dysbindin or
      Drosophila NSF. However, neither reduction of NSF alone or in combination with
      dysbindin haploinsufficiency impaired homeostatic synaptic plasticity. Our
      results demonstrate that dysbindin/BLOC-1 expression defects result in altered
      cellular content of proteins of the vesicle fusion apparatus and therefore
      influence synaptic plasticity. 

PMID- 25972188
TI  - Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a
      novel alternative for confirmation testing in resource limited settings.
AB  - BACKGROUND: Current WHO testing guidelines for resource limited settings diagnose
      HIV on the basis of screening tests without a confirmation test due to cost
      constraints. This leads to a potential risk of false positive HIV diagnosis. In
      this paper, we evaluate the dilution test, a novel method for confirmation
      testing, which is simple, rapid, and low cost. The principle of the dilution test
      is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the
      sample, in order to screen out the cross reacting antibodies responsible for
      falsely positive RDT results. METHODS: Participants were recruited from two
      testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs
      in series is used to diagnose HIV. All samples positive on the initial screening
      RDT and every 10th negative sample underwent testing with the gold standard and
      dilution test. Dilution testing was performed using DetermineTM rapid diagnostic
      test at 6 different dilutions. Results were compared to the gold standard of
      Western Blot; where Western Blot was indeterminate, PCR testing determined the
      final result. RESULTS: 2895 samples were recruited to the study. 247 were
      positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent
      dilution testing. The RDT diagnostic algorithm misclassified 18 samples as
      positive. Dilution at the level of 1/160 was able to correctly identify all these
      18 false positives, but at a cost of a single false negative result (sensitivity
      99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance
      between the gold standard and the 1/160 dilution strength was 99.8 %. CONCLUSION:
      This study provides proof of concept for a new, low cost method of confirming HIV
      diagnosis in resource-limited settings. It has potential for use as a
      supplementary test in a confirmatory algorithm, whereby double positive RDT
      results undergo dilution testing, with positive results confirming HIV infection.
      Negative results require nucleic acid testing to rule out false negative results
      due to seroconversion or misclassification by the lower sensitivity dilution
      test. Further research is needed to determine if these results can be replicated
      in other settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01716299 .

PMID- 25972191
TI  - General considerations in ocular toxicity risk assessment from the toxicologists'
      viewpoints.
AB  - Humans commonly obtain approximately 80% of external information from vision.
      Since loss of vision markedly decreases quality of life, risk assessments for
      visual toxicity of new drugs are extremely important. However, the ICH S4
      guideline for nonclinical toxicity study of new drugs only indicates a brief
      instruction for ophthalmologic examinations, and submitted data for drug approval
      according only to this guideline are not always considered sufficient in light of
      ocular toxicity risk assessments. The eye is an assembly of many specialized sub
      organs which have specific functions, and its integral maintenance of homeostasis
      plays an important role of visual function. When only a part of integrity of
      functions is lost, overall function of the eye might be commonly disturbed.
      Therefore, understanding of anatomy and physiology of these sub-organs may help
      know mechanisms of observed ocular changes. In ophthalmologic examinations in
      nonclinical toxicity studies, it is vital to understand the principles and
      features of each examination. Comparisons of findings between pre and post drug
      treatment as well as considerations of species differences, strain differences,
      age differences, and location/degree of abnormalities are essential. In addition,
      many kinds of spontaneous ocular findings are well known in experimental animals.
      To differentiate treatment-related changes from spontaneous findings, mastering
      basic skills for ophthalmologic examinations and taking advantage of collection
      of background data are necessary. For ocular toxicity risk assessments, while an
      evaluation of "sight-threatening" effects is most critical matter, "quality of
      vision" related findings also should be considered. To extrapolate animal data to
      human, clinical significances of ocular toxicity findings should be evaluated
      based on considerations for "species differences", "safety margins",
      "reversibility", and "risk-benefit balance". In addition, a detailed recording of
      features of lesions is also important for an appropriate judgment of clinical
      significance of ocular findings. For preparation of histopathological specimens,
      careful sampling of organs and suitable selection of fixatives are important. To
      accurately orient ocular lesions in the specimen for histopathological
      examinations, securing close communications prior to necropsy among
      ophthalmologists, gross necropsy pathologists and histopathology technicians
      should be effective and helpful. It is impossible to detect all ocular changes in
      histopathological examinations; that is, there is a limitation in
      histopathological examinations. Therefore, for ocular toxicity risk assessments,
      comprehensive evaluation with pathological findings as well as other results of
      various examinations in toxicity studies should be considered. In conclusion, for
      ocular toxicity risk assessments, integrated judgments from all examination data
      in nonclinical toxicity studies are required. To achieve appropriate risk
      assessments which can be extrapolated to human, close communications and sharing
      of data regarding the eye are most important among toxicologists, clinical sign
      investigators, histopathology technicians and pathologists. 

PMID- 25972190
TI  - IL-23/IL-17A Dysfunction Phenotypes Inform Possible Clinical Effects from Anti-IL
      17A Therapies.
AB  - Biologics that neutralize specific cytokines have improved outcomes for several
      immune-mediated disorders but may also increase risks for particular side
      effects. This article postulates potential immunologic consequences of inhibiting
      components of the IL-23/T-helper cell 17 pathway-the target of next-generation
      biologics for treating psoriasis-based on clinical phenotypes of inherent or
      acquired deficiencies in this pathway. Generally, downstream deficiencies (e.g.,
      IL-17A, IL-17F) are associated with fewer disorders compared with upstream
      deficiencies, suggesting that selectively blocking downstream targets may result
      in a narrower range of side effects. However, safety of these specific
      inhibitions must be established in long-term studies. 

PMID- 25972192
TI  - Thyroid and growth hormone concentrations in 8-year-old children exposed in utero
      to dioxins and polychlorinated biphenyls.
AB  - The objective of this study was to examine the effects of in utero exposure to
      polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins,
      dibenzofurans (PCDD/F) on thyroid and growth hormone concentrations and growth in
      8-year-old children. A total of 56 children (23 boys, 33 girls) were included in
      the study. All were stratified into high and low PCDD/F + PCB exposure groups
      based on maternal median indicator PCB and PCDD/F + PCB concentrations during
      pregnancy. Height, weight, body mass index, and thyroid and growth hormone
      concentrations were assessed and compared among the different exposure groups.
      There were no significant effects of indicator PCB or PCDD/F + PCB exposure
      levels on growth (height, weight, and bone age) among 8-year-old boys or girls.
      Boys exposed to high PCDD/F + PCB levels had significantly higher thyroxine
      binding globulin (TBG) concentrations than boys exposed to low levels (P =
      0.027). Girls exposed to high PCB levels had significantly lower IGF-binding
      protein-3 (IGFBP-3) concentrations than girls exposed to low levels (P = 0.038).
      Low levels of in utero exposure to PCDD/F+PCB and high indicator PCB levels were
      significantly associated with reduced serum concentrations of IGFBP-3. High
      levels of in utero exposure to PCDD/F+PCB plus either high or low indicator PCB
      levels were significantly associated with increased serum concentrations of
      growth hormone, T3, T4, and TBG. These findings suggest that the level of in
      utero exposure to PCBs and dioxins may affect serum concentrations of growth
      hormone, thyroid hormones, TBG, and IGFBP-3 in 8-year-old children. 

PMID- 25972193
TI  - The cytotoxicity of organobismuth compounds with certain molecular structures can
      be diminished by replacing the bismuth atom with an antimony atom in the
      molecules.
AB  - Organic-inorganic hybrid molecules, which are composed of an organic structure
      and metal(s), are indispensable for synthetic chemical reactions; however, their
      toxicity has been incompletely understood. In the present study, we discovered
      two cytotoxic organobismuth compounds whose cytotoxicity diminished upon
      replacement of the intramolecular bismuth atom with an antimony atom. The
      intracellular accumulation of the organobismuth compounds was much higher than
      that of the organoantimony compounds with the corresponding organic structures.
      We also showed that both the organic structure and bismuth atom are required for
      certain organobismuth compounds to exert their cytotoxic effect, suggesting that
      the cytotoxicity of such a compound is a result of an interaction between the
      organic structure and the bismuth atom. The present data suggest that
      organobismuth compounds with certain molecular structures exhibit cytotoxicity
      via an interaction between the molecular structure and the bismuth atom, and this
      cytotoxicity can be diminished by replacing the bismuth atom with an antimony
      atom, resulting in lower intracellular accumulation. 

PMID- 25972194
TI  - Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under
      oxidative stress through the expression of DDR genes.
AB  - Oxidative stress is linked to increased risk of gastric cancer (GC). Recent
      reports have found that hsa-let-7 g microRNA (miRNA) has properties of anti-tumor
      and resistance to damages induced by oxidized low-density lipoprotein (ox-LDL).
      Dysregulation of hsa-let-7 g was present in GC in vivo and in vitro under
      exogenous stress. However, we didn't know whether there are regulatory mechanisms
      of hsa-let-7 g in GC under oxidative stress. This study was aimed at
      investigating the effects of hsa-let-7 g microRNA (miRNA) on GC under oxidative
      stress. The results showed that H2O2 induced the increase of DNA damage response
      (DDR) genes (ATM, H2AX and Chk1) and downregulation of hsa-let-7 g in GC cells.
      Further study confirmed Hsa-let-7 g caused the apoptosis and loss of
      proliferation in GC cells exposed to H2O2 associated with repression of DDR
      system. Yet, we found let-7 g didn't target DDR genes (ATM, H2AX and Chk1)
      directly. In addition, data revealed hsa-let-7 g miRNA increased the sensitivity
      of GC to X-rays involving in ATM regulation as well according to application of X
      rays (another DDR inducer). In conclusion, Hsa-let-7 g miRNA increased the
      sensitivity of GC to oxidative stress by repression activation of DDR indirectly.
      Let-7 g improved the effects of X-rays on GC cells involving in DDR regulation as
      well.

PMID- 25972195
TI  - Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation
      of murine electrocardiography parameters.
AB  - Our in vitro characterization showed that physiological concentrations of
      estrogen partially suppressed the I(Kr) channel current in guinea pig ventricular
      myocytes and the human ether-a-go-go-related gene (hERG) channel currents in CHO
      K1 cells regardless of estrogen receptor signaling and revealed that the
      partially suppressed hERG currents enhanced the sensitivity to the hERG blocker E
      4031. To obtain in vivo proof-of-concept data to support the effects of estrogen
      on cardiac electrophysiology, we here employed an aromatase knockout mouse as an
      in vivo estrogen-null model and compared the acute effects of E-4031 on cardiac
      electrophysiological parameters with those in wild-type mice (C57/BL6J) by
      recording surface electrocardiogram (ECG). The ablation of circulating estrogens
      blunted the effects of E-4031 on heart rate and QT interval in mice under a
      denervation condition. Our result provides in vivo proof of principle and
      demonstrates that endogenous estrogens increase the sensitivity of E-4031 to
      cardiac electrophysiology.

PMID- 25972196
TI  - The role of NF-kappaB in PARP-inhibitor-mediated sensitization and detoxification
      of arsenic trioxide in hepatocellular carcinoma cells.
AB  - The therapeutic efficacy of arsenic trioxide (ATO) for treatments of solid tumors
      is restricted by its drug resistance and chemotoxicity. In this study, we
      investigated ATO sensitization and detoxification effect of the Poly (ADP ribose)
      polymerase-1 (PARP-1) inhibitor 4-Amino-1,8-naphthalimide (4AN) in the
      hepatocellular carcinoma cell line HepG2. We firstly reported that ATO treatment
      induced the activation of Nuclear factor of kappaB (NF-kappaB) and its downstream
      anti-apoptosis and pro-inflammatory effectors in a PARP-1-dependent manner and
      thus conferred HepG2 cells with ATO resistance and toxicity. 4AN significantly
      suppressed the ATO-induced NF-kappaB activation, which promotes the apoptotic
      response and alleviates the inflammatory reaction induced by ATO, resulting in
      sensitization and detoxification against ATO. We also demonstrated that the ATO
      induced activation of PARP-1 and NF-kappaB was closely associated with the
      oxidative DNA damage mediated by the generated reactive oxygen species (ROS).
      Furthermore, the attenuation of ATO-induced ROS and the resulting oxidative DNA
      damage by N-acetyl-L-cysteine (NAC), a potent antioxidant, significantly reduced
      the activation of PARP-1 and NF-kappaB in ATO-treated cells. Our study provides
      novel insights into the mechanism of the PARP-1-mediated NF-kappaB signaling
      pathway in ATO resistance and toxicity in anticancer treatments. This study also
      highlights the application potential of PARP-1 inhibitors in ATO-based anti
      cancer treatments and in prevention of NF-kappaB-mediated therapeutic resistance
      and toxicity. 

PMID- 25972197
TI  - MicroRNA profiling in ethylene glycol monomethyl ether-induced monkey testicular
      toxicity model.
AB  - To establish and characterize ethylene glycol monomethyl ether (EGME)-induced
      testicular toxicity model in cynomolgus monkeys, EGME at 0 or 300 mg/kg was
      administered orally to sexually mature male cynomolgus monkeys (n = 3/group) for
      4 consecutive days. Circulating and testicular microRNA (miRNA) profiles in this
      model were investigated using miRNA microarray or real-time quantitative reverse
      transcription-PCR methods. EGME at 300 mg/kg induced testicular toxicity in all
      the monkeys, which was characterized histopathologically by decreases in
      pachytene spermatocytes and round spermatids, without any severe changes in
      general conditions or clinical pathology. In microarray analysis, 16 down
      regulated and 347 up-regulated miRNAs were detected in the testis, and 326 down
      regulated but no up-regulated miRNAs were detected in plasma. Interestingly, miR
      1228 and miR-2861 were identified as abundant miRNAs in plasma and the testis of
      control animals, associated presumably with apoptosis and cell differentiation,
      respectively, and were prominently increased in the testis of EGME-treated
      animals, reflecting the recovery from EGME-induced testicular damages via
      stimulating cell proliferation and differentiation of sperm. Furthermore, down
      regulation of miR-34b-5p and miR-449a, which are enriched in meiotic cells like
      pachytene spermatocytes, was obvious in the testis, suggesting that these
      spermatogenic cells were damaged by the EGME treatment. In conclusion, EGME
      induced testicular toxicity in cynomolgus monkeys was shown, and this model would
      be useful for investigating the mechanism of EGME-induced testicular toxicity and
      identifying testicular biomarkers. Additionally, testicular miR-34b-5p and miR
      449a were suggested to be involved in damage of pachytene spermatocytes. 

PMID- 25972198
TI  - Chromium (VI)-induced transformation is enhanced by Zn deficiency in BALB/c 3T3
      cells.
AB  - Hexavalent chromium [Cr(VI)] is a carcinogenic heavy metal that is reduced to
      intermediate oxidation states, such as Cr(V) and Cr(IV), in the process of
      forming stable Cr(III) forms; it is these intermediate forms that are thought to
      be responsible for much of the DNA damage and mutations that are induced by
      Cr(VI). Metallothionein (MT), a heavy metal-binding protein, is induced by zinc
      and other heavy metals and protects cells from the toxic effects of these metals
      by sequestering them. MT cannot bind Cr, but by scavenging reactive oxygen
      species through its cysteine residues, it may act as a protective factor against
      Cr(VI)-induced DNA lesions by reducing Cr(VI) directly to Cr(III), thereby
      avoiding the creation of the toxic intermediates. Here, we showed that Zn
      deficiency decreased MT expression in BALB/3T3 clone A31-1-1 cells and caused
      them to become highly susceptible to Cr(VI)-induced transformation. To obtain Zn
      deficient cultures, cells were cultured in medium supplemented with 10%
      Chelex((r))-100 chelating resin-treated FBS. The increase in susceptibility to
      transformation was abolished by culturing the cells with supplemental Zn (50 uM).
      Previously, we reported that Cr(VI) inhibits MT transcription by preventing the
      zinc-dependent formation of a complex of metal response element-binding
      transcription factor-1 (MTF-1) and the co-activator p300. Our results suggest
      that the carcinogenicity of Cr(VI) is enhanced by MTF-1 dysfunction. 

PMID- 25972199
TI  - Hepatotoxicants induce cytokine imbalance in response to innate immune system.
AB  - In recent years, attention has been paid to innate immune systems as mechanisms
      to initiate or promote drug-induced liver injury (DILI). Kupffer cells are
      hepatic resident macrophages and might be involved in the pathogenesis of DILI by
      release of pro- and anti-inflammatory mediators such as cytokines, chemokines,
      reactive oxygen species, and/or nitric oxides. The purpose of this study was to
      investigate alterations in mediator levels induced by hepatotoxic compounds in
      isolated Kupffer cells and discuss the relation between balance of each cytokine
      or chemokine and potential of innate immune-mediated DILI. Primary cultured rat
      Kupffer cells were treated with hepatotoxic (acetaminophen, troglitazone,
      trovafloxacin) or non-hepatotoxic (pioglitazone, levofloxacin) compounds with or
      without lipopolysaccharide (LPS). After 24 hr treatment, cell supernatants were
      collected and various levels of mediators released by Kupffer cells were
      examined. Although hepatotoxicants had no effect on the LPS-induced tumor
      necrosis factor-alpha (TNF-alpha) secretion, they enhanced the release of pro
      inflammatory cytokine interleukin-1 beta (IL-1beta) and suppressed the anti
      inflammatory cytokines interleukin-6 (IL-6) and interleukin-10 (IL-10) induced by
      LPS. These cytokine shifts were not associated with switching the phenotypes of
      M1 and M2 macrophages in Kupffer cells. In conclusion, the present study
      suggested that the levels of some specific cytokines are affected by DILI-related
      drugs with LPS stimulation, and imbalance between pro- and anti-inflammatory
      cytokines, induced by the up-regulation of IL-1beta and the down-regulation of IL
      6 or IL-10, plays a key role in innate immune-mediated DILI. 

PMID- 25972200
TI  - A Biotin-PEAC5-maleimide labeling assay to detect electrophiles.
AB  - Recently, we established a biotin-PEAC5-maleimide (BPM)-labeling assay, which can
      be used to determine the modification of electrophilic metals to proteins (Toyama
      et al., J. Toxicol. Sci., 38, 477-484, 2013). In the present study, we applied a
      BPM-labeling assay to detect protein S-modification by environmental organic
      electrophiles. After exposing A431 cells to 1,2-naphthoquinone (1,2-NQ) and 1,4
      naphthoquinone (1,4-NQ), there was an inverse correlation between Western blot
      analysis with specific antibody against these electrophiles and that with BPM on
      the blot intensity to detect protein modification. Similar results were also
      observed using enzyme-linked immunosorbent assay (ELISA) with BPM. Modification
      of proteins in mouse liver cytosol by 5-hydroxy-1,4-NQ, 5,8-dihydroxy-1,4-NQ, 1,4
      benzoquinone (1,4-BQ), tert-butyl-1,4-BQ, and N-acetyl-p-benzoquinoneimine, an
      electrophilic metabolite of acetaminophen, was detected using ELISA, but not non
      electrophilic quinones or hydroquinone. We also tested whether ELISA could be
      used to detect electrophiles contained in the vapor phase of ambient air samples
      collected in the midtown area of Los Angeles. Taken together, the results
      suggested that the ELISA, developed in this study, can detect the existence of
      electrophilic quinones that covalently modify cellular proteins, resulting in
      modulation of redox-signal transduction pathways or cell damage. 

PMID- 25972201
TI  - Altered gene expression profile in ovarian follicle in rats treated with
      indomethacin and RU486.
AB  - It is well-known that indomethacin (the cyclooxygenase 1 & 2 inhibitor) and RU486
      (or mifepristone, the progesterone receptor antagonist) block follicular rupture
      in rats. To characterize genetic alterations in unruptured follicles, gene
      expression profiles in ovarian follicle were analyzed in indomethacin- and RU486
      treated female Sprague-Dawley rats. Ovaries are collected at 22:00 on the
      proestrus day and 10:00 on the following estrus day after a single dose of
      indomethacin and RU486. Histopathologically, changes depicting responses to LH
      surge were observed in ovaries, uteri and vagina. Total RNA was extracted from
      pre-ovulatory follicles or unruptured follicles collected by laser
      microdissection and analyzed by Genechip((r)). Among genes showing statistically
      significant changes compared to control groups, following changes were considered
      relevant to induction of unruptured follicles. In indomethacin-treated rats, Wnt4
      was down-regulated, suggesting effect on tissue integrity and steroid genesis. In
      RU486-treated rats, Adamts1, Adamts9, Edn2, Ednra, Lyve1, Plat, and Pparg were
      down-regulated. These changes suggest effects on proteolysis for extra cellular
      matrix or surrounding tissue (Adamts1 & 9, and Plat), constriction of smooth
      muscle surrounding follicles (Edn2, Ednra, and Pparg), follicular fluid (Lyve1),
      and angiogenesis (Pparg). Down-regulation of angiogenesis related genes (Angpt2,
      Hmox1, and Vegfa) was observed in both treatment groups. Here, we clarify genetic
      alterations induced by the inhibition of cyclooxygenase or progesterone receptor.

PMID- 25972202
TI  - Anniversary of the discovery of sec mutants by Novick and Schekman.
AB  - This year marks the 35th anniversary of the isolation of 23 SEC genes. These
      genes all encode key regulators of the secretory pathway, and much of our
      knowledge of the secretory pathway is based on this initial discovery. The
      identification of the SEC genes is a result of combining genetics, biochemistry,
      and electron microscopy in a very clever way. Scientists have been busy ever
      since seeking to understand the function and regulation of these genes and to
      identify further key players in the process. Although most of the machinery
      acting along the secretory pathway is known and its function generally
      understood, knowledge of regulation of the pathway under various conditions is
      still scarce and will keep researchers busy for years to come. 

PMID- 25972203
TI  - Improving health-related fitness in adolescents: the CrossFit TeensTM randomised
      controlled trial.
AB  - The aim of this study was to evaluate the preliminary efficacy and feasibility of
      the CrossFit TeensTM resistance training programme for improving health-related
      fitness and resistance training skill competency in adolescents. This assessor
      blinded randomised controlled trial was conducted in one secondary school in the
      Hunter Region, Australia, from July to September 2013. Ninety-six (96) students
      (age = 15.4 (.5) years, 51.5% female) were randomised into intervention (n = 51)
      or control (n = 45) conditions for 8-weeks (60 min twice per week). Waist
      circumference, body mass index (BMI), BMI-Z score (primary outcomes),
      cardiorespiratory fitness (shuttle run test), muscular fitness (standing jump,
      push-up, handgrip, curl-up test), flexibility (sit and reach) and resistance
      training skill competency were measured at baseline and immediate post
      intervention. Feasibility measures of recruitment, retention, adherence and
      satisfaction were assessed. Significant group-by-time intervention effects were
      found for waist circumference [-3.1 cm, P < 0.001], BMI [-1.38 kg . m(-)(2), P <
      0.001], BMI-Z [-0.5 z-scores, P < 0.001], sit and reach [+3.0 cm, P < 0.001],
      standing jump [+0.1 m, P = 0.021] and shuttle run [+10.3 laps, P = 0.019].
      Retention rate was 82.3%. All programme sessions were delivered and participants'
      mean satisfaction scores ranged from 4.2 to 4.6 out of 5. The findings
      demonstrate that CrossFit TeensTM is a feasible and efficacious programme for
      improving health-related fitness in adolescents.

PMID- 25972204
TI  - Renal function can be impaired in children with primary hyperoxaluria type 3.
AB  - BACKGROUND: Primary hyperoxaluria type 3 (PH3) is characterized by mutations in
      the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are believed to
      present with a less severe phenotype than those with PH1 and PH2, but the
      clinical characteristics of PH3 patients have yet to be defined in sufficient
      detail. The aim of this study was to report our experience with PH3. METHODS:
      Genetic analysis of HOGA1 was performed in patients with a high clinical
      suspicion of PH after the presence of mutations in the alanine-glyoxylate
      aminotransferase gene had been ruled out. Clinical, biochemical and genetic data
      of the seven patients identified with HOGA1 mutations were subsequently
      retrospectively reviewed. RESULTS: Among the seven patients identified with HOGA1
      mutations the median onset of clinical symptoms was 1.8 (range 0.4-9.8) years.
      Five patients initially presented with urolithiasis, and two other patients
      presented with urinary tract infection. All patients experienced persistent
      hyperoxaluria. Seven mutations were found in HOGA1, including two previously
      unreported ones, c.834 + 1G > T and c.3G > A. At last follow-up, two patients had
      impaired renal function based on estimated glomerular filtration rates (GFRs) of
      77 and 83 mL/min per 1.73 m(2), respectively. CONCLUSIONS: We found that the GFR
      was significantly impaired in two of our seven patients with PH3 diagnosed during
      childhood. This finding is in contrast to the early-impaired renal function in
      PH1 and PH2 and appears to refute to preliminary reassuring data on renal
      function in PH3.

PMID- 25972205
TI  - Non-prescription treatment of NSAID induced GORD by Australian pharmacies: a
      national simulated patient study.
AB  - BACKGROUND: Patients regularly present to community pharmacies for advice about
      and treatment for reflux symptoms and NSAIDs are a common cause of these
      symptoms. There is no published literature detailing the approach that pharmacies
      take to these enquiries, the pharmacotherapy they recommend or whether they
      contribute to the safe and effective use of reflux medicines. OBJECTIVES: To
      assess in an observational study design the clinical history gathering,
      recommendations for GORD management and counselling provided by community
      pharmacies in a simulated patient scenario involving suspected NSAID induced
      reflux symptoms. Setting Australian community pharmacies. METHOD: Simulated
      patients visited 223 community pharmacies to request treatment for reflux
      symptoms. The interaction was audiotaped and assessed against guidelines for the
      treatment of reflux symptoms. MAIN OUTCOME MEASURES: Alignment of community
      pharmacies with international expert gastroenterologist guidance and national
      professional practice guidelines for the treatment of reflux symptoms by
      pharmacists including: consultation with a pharmacist; confirmation of reflux
      diagnosis based on symptoms; recommendation of short courses proton pump
      inhibitor (PPI) therapy; advice on the safe and effective use of reflux medicines
      and referral to a doctor for further assessment. RESULTS: Pharmacists consulted
      with the simulated patient in 77% of cases. Symptoms were enquired about in 95%
      of cases and a medicines history taken in 69% of cases. Recommendations for
      treatment included: PPIs (18%), histamine H2 antagonists (57%) and antacids
      (19%). Advice on product use was given in 83% of cases. Referral to a doctor to
      discuss reflux symptoms was made in 63% of cases. CONCLUSION: When assessing
      patients for the symptoms of GORD, Australian pharmacists and non-pharmacist
      support staff take a comprehensive history including symptomatology, duration of
      symptoms, concomitant medicines and medical conditions and any GORD treatments
      previously trialled. They provide comprehensive counselling on the use of
      antisecretory and antacid medicines. Counselling could involve more comprehensive
      information on lifestyle approaches for GORD management and side effects of
      antisecretory and antacid medicines. Further alignment with guidelines for the
      management of GORD would result in greater referral to a doctor for assessment of
      recurrent GORD and greater recommendation of PPIs for symptoms. However alignment
      with guidelines by all pharmacists is unrealistic if the guidelines are not
      universally available to them.

PMID- 25972207
TI  - Commentary on "impact of trainees on length of stay in the emergency department
      at an academic medical center".

PMID- 25972206
TI  - Impact of trainees on length of stay in the emergency department at an Academic
      Medical Center.
AB  - OBJECTIVES: Emergency department (ED) overcrowding remains a growing concern
      despite continued efforts by hospitals to improve efficiency while also
      maintaining quality of care and medical education. The purpose of this study was
      to examine whether the total number of trainees rotating in the ED affects length
      of stay (LOS). METHODS: This was a single-center study conducted at an urban
      university teaching hospital and level I trauma center that averages 65,000 adult
      ED visits per year. Data were collected retrospectively during a 13-month period
      from September 2012 to September 2013. The mean daily LOS was generated by the
      hospital's electronic medical record system, and the total number of trainees
      (medical students, postgraduate year-1 students/interns, and nurse practitioners)
      rotating in the ED each day was collected from monthly shift calendars.
      Correlations were used to examine the relation between LOS and number of trainees
      rotating in the ED. Independent sample t tests were conducted to compare
      differences in average LOS on days with and without trainees rotating in the ED.
      RESULTS: The mean daily LOS ranged from 3.39 to 7.13 hours (mean 4.97, standard
      deviation [SD] 0.59). The number of trainees rotating in the ED each day ranged
      from 0 to 11 (mean 5.32, SD 2.39). No significant relation was found between LOS
      and the number of trainees rotating in the ED (r = 0.06). Subsequent analyses
      using independent sample t test revealed that LOS did not vary even when no
      trainees were rotating in the ED (mean 4.93, SD 0.69) versus when at least one
      trainee was working (mean 4.97, SD 0.59). CONCLUSIONS: Findings from this study
      suggest that ED LOS is unaffected by the presence or total number of trainees
      (medical students, postgraduate year-1 students/interns, and nurse practitioners)
      rotating in the ED. Further research is needed to examine what, if any,
      adjustments are being made to accommodate trainees and whether the quality of
      education suffers when the trainee-to-attending ratio is high.

PMID- 25972208
TI  - Don't order a test just because you can.

PMID- 25972209
TI  - Pediatric Staphylococcus aureus Infections: Impact of Methicillin Resistance at a
      Canadian Center.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide
      spectrum of potentially serious infections in children. This study describes the
      evolving experience with S. aureus infections at a Canadian tertiary pediatric
      care center serving a wide geographic area. DESIGN: In this two-component study,
      a retrospective review of infection control databases for MRSA infection was
      conducted, along with a prospective component for 1 year during which all
      community-onset S. aureus infections were identified. Cases with methicillin
      resistance and susceptibility were compared. RESULTS: Review of infection control
      database records showed 239 unique infections, with steady increases over time.
      Common pulsed-field gel electrophoresis types included Canadian MRSA-7 and
      Canadian MRSA-10. During the 1-year prospective component, 210 clinical
      infections were identified, with MRSA isolated in 41%. Patients with MRSA were
      significantly younger than those with methicillin-susceptible isolates (4.9 vs
      7.7 years, P < 0.001). The most common presentations were soft tissue infections
      in the emergency department, with a degree of inappropriate antimicrobial use.
      CONCLUSIONS: MRSA contributed to a significant proportion of S. aureus infections
      at a large Canadian tertiary care center. Ample opportunities exist to develop
      stewardship protocols, especially for the management of soft tissue infections in
      outpatients.

PMID- 25972210
TI  - Insurance status effects on stage of diagnosis and surgical options used in the
      treatment of breast cancer.
AB  - OBJECTIVES: Insurance status has the potential to play a significant role in an
      individual's health care by affecting the time of diagnosis and the treatment
      options used. Our study reviewed insurance status as a determinant of the time of
      a breast cancer diagnosis as well as the surgical treatment options offered.
      METHODS: The American College of Surgeons' National Cancer Database benchmark
      reports were used to examine first-course surgery stratified by the stage of
      breast cancer diagnosed between 2000 and 2010. The data were stratified according
      to insurance status with a focus on insured patients versus underinsured
      patients. The relations among insurance status, breast cancer stage at the time
      of presentation, and initial treatment offered were then evaluated. RESULTS:
      There was a statistically significant relation between breast cancer stage at the
      time of diagnosis and insurance status. There also was a relation between
      insurance status and the treatment offered. Adequately insured patients presented
      at an earlier stage than did underinsured patients. In addition, in patients who
      present with early-stage disease, insured patients had a higher rate of breast
      conserving surgery than did underinsured patients, 62.4% and 55.5%, respectively.
      This trend continued in late-stage breast cancer, in which mastectomy was the
      predominant treatment option overall. Despite this, insured patients underwent
      breast-conserving therapy more frequently than did underinsured patients, 24.2%
      and 21.2%, respectively. CONCLUSIONS: The discrepancy of the stage of diagnosis
      between insured patients and underinsured patients can be attributed to a host of
      factors, among which are access to regular office visits and screening tests for
      breast cancer. In addition, the surgical treatment options used may depend on the
      cost of treatment and accessibility to and compliance with follow-up care.

PMID- 25972211
TI  - Lawyer mothers: infant-feeding intentions and behavior.
AB  - OBJECTIVES: Maternal employment postpartum can have a powerful influence over
      infant-feeding behaviors. The objective of this cross-sectional online survey was
      to explore the infant-feeding intentions and behaviors of a convenience sample of
      lawyer mothers. We compared our findings with those for physician mothers.
      METHODS: Lawyers participated in an anonymous online survey. To eliminate the
      influence of multiple births, only study subjects with one child were reviewed
      for inclusion in this analysis. We used SPSS for calculation of descriptive
      statistics, the Mann-Whitney test for comparisons, and the Spearman rank
      correlation test for testing correlations. RESULTS: All mothers (29 lawyers and
      47 physicians) included in the final analysis reported an intention to breast
      feed, with 55% of lawyers wanting to breast-feed for at least 12 months.
      Physicians' breast-feeding rates were 98% at birth, 83% at 6 months, and 51% at
      12 months. Lawyers' breast-feeding rates were 100% at birth, 55% at 6 months, and
      17% at 12 months. Their duration of breast-feeding correlated with the support
      level at work and the sufficiency of time and availability of appropriate places
      at work to express milk. CONCLUSIONS: This study did not detect statistically
      significant differences in infant-feeding intentions and behaviors of lawyer
      mothers when compared with physician mothers. Although the majority of lawyer
      mothers intended to breast-feed for at least 12 months, only a minority achieved
      that goal. Our findings support the development of workplace strategies and
      programs to promote breast-feeding duration among lawyers returning to work after
      childbirth.

PMID- 25972212
TI  - Effectiveness of an urban emergency department call-back system in the successful
      linkage to treatment of sexually transmitted infections.
AB  - OBJECTIVES: There is a high incidence of asymptomatic sexually transmitted
      infections (STIs) in emergency department (ED) patients. There is no historical
      indication, physical examination finding, or rapidly available laboratory testing
      specific for detecting STIs in women. This study was conducted to describe the
      performance of an ED call-back system for STI screening and linkage to care for
      treatment. Success was defined as the ability to contact STI-positive women who
      were undertreated and confirm their return for definitive treatment. METHODS:
      This retrospective, observational study of women 16 years and older evaluated
      those undertreated for STIs in the ED during the 13-month study period. A
      structured chart review was performed to determine the proportion of patients
      returning to an affiliated hospital ED or clinic for treatment after contact by
      telephone or letter. RESULTS: Of 361 patients identified as undertreated, 29.4%
      (95% confidence interval [CI] 24.7-34.1) did not return for definitive treatment.
      The method of contact was associated with patient return for treatment. Of the
      276 patients contacted by telephone, 19.6% did not return for treatment (95% CI
      14.9-24.3); of the 83 patients contacted by letter, 60.2% did not return for
      treatment (95% CI 49.7-70.8; P < 0.0001). CONCLUSIONS: A large proportion of
      patients undertreated for an STI did not return despite a notification of need
      for further treatment. This study had a high rate of successful telephone contact
      (76.5%), but contact did not substantially increase the overall proportion of
      patients who were linked to care and returned to the ED for treatment.

PMID- 25972213
TI  - Commentary on "Effectiveness of an urban emergency department call-back system in
      the successful linkage to treatment of sexually transmitted infections".

PMID- 25972214
TI  - Factors associated with emergency department visits in asthma exacerbation.
AB  - OBJECTIVES: Despite quality improvement initiatives to prevent asthma-related
      emergency department (ED) visits, rates have not declined. We sought to determine
      factors associated with ED visits in an underserved population. METHODS: We
      performed a case-control analysis of asthma patients at three ambulatory care
      centers serving low-income populations. Cases consisted of asthmatic patients
      aged 18 to 45 years with >=1 ED visit for an asthma exacerbation between August
      1, 2008 and July 31, 2010. Controls were patients with asthma aged 18 to 45 years
      with >=1 outpatient visit during the same period but with no asthma-related ED
      visit. Data were collected by chart review and included demographics, past
      referral for asthma education or to a pulmonologist, recent tobacco use,
      influenza vaccination, and asthma medication prescriptions in the year before the
      index visit. RESULTS: Among 244 cases and 475 controls, there were no significant
      differences in age, sex, or ethnicity. Cases were more likely than controls to
      have ever been referred for asthma education (odds ratio [OR] 4.09, 95%
      confidence interval [CI] 2.57-6.50) or to a pulmonologist (OR 2.31, 95% CI 1.15
      4.66). In the year before the index visit, cases were more likely than controls
      to receive other medications in addition to inhaled corticosteroids (ICS; OR
      1.74, 95% CI 1.14-2.66) but less likely to receive influenza vaccination (OR
      0.49, 95% CI 0.34-0.71), a short-acting beta-agonist (OR 0.43, 95% CI 0.24-0.78),
      or ICS alone (OR 0.53, 95% CI 0.34-0.84). CONCLUSIONS: Markers of severe disease
      were associated with ED visits, as well as a lack of an influenza vaccination and
      failure to prescribe either ICS or short-acting beta-agonists.

PMID- 25972215
TI  - Commentary on "Factors associated with emergency department visits in asthma
      exacerbation".

PMID- 25972216
TI  - Factors associated with local public health agency participation in obesity
      prevention in southern States.
AB  - OBJECTIVES: Obesity rates in the southern US states are higher than in other
      states. Historically, large-scale community-based interventions in the United
      States have not proven successful. With local public health agencies (LPHAs)
      tasked with prevention, their role in obesity prevention is important, yet little
      research exists regarding what predicts the participation of LPHAs. METHODS:
      Cross-sectional data from the 2008 National Association of City and County Health
      Officials profile study and two public health conceptual frameworks were used to
      assess structural and environmental predictors of LPHA participation in obesity
      prevention. The predictors were compared between southern and nonsouthern states.
      Univariate and weighted logistic regressions were performed. RESULTS: Analysis
      revealed that more LPHAs in southern states were engaged in nearly all of the 10
      essential public health functions related to obesity prevention compared with
      nonsouthern states. Presence of community-based organizations and staffing levels
      were the only significant variables in two of the six logistic regression models.
      CONCLUSIONS: This study provides insights into the success rates of the obesity
      prevention efforts of LPHAs in southern and nonsouthern states. Future research
      is needed to understand why and how certain structural elements and any
      additional factors influence LPHA participation in obesity prevention.

PMID- 25972218
TI  - Moving Away from Fee-for-Service: Implications for Medication Adherence.

PMID- 25972217
TI  - Utilization of 2013 BRFSS Physical Activity Data for State Cancer Control Plan
      Objectives: Alabama Data.
AB  - OBJECTIVES: All comprehensive US cancer control plans mention physical activity
      and implement physical activity promotion objectives as part of these cancer
      plans. The purpose of this investigation was to describe the physical activities
      reported by Alabama adults in the 2013 Behavioral Risk Factor Surveillance System
      (BFRSS) and to compare these activities by age group and relative exercise
      intensity. METHODS: This investigation used data on 6503 respondents from the
      2013 BRFSS sample of respondents from Alabama with landline and cellular
      telephones. Respondents were asked whether they engaged in any physical
      activities or aerobic exercises such as running, calisthenics, golf, gardening,
      or walking. Information was collected on strengthening activities such as yoga,
      sit-ups, push-ups, and using weight machines, free weights, and elastic bands.
      Relative exercise intensity was estimated for each aerobic activity by comparing
      the 60% maximal oxygen uptake with metabolic equivalent values. RESULTS:
      Approximately two-thirds (63.7%) of respondents reported that they engaged in
      exercise in the past 30 days; 45.4% participated in enough aerobic activity per
      week to meet guidelines, and 25.9% met the muscle-strengthening guidelines. Only
      10.1% of respondents 65 years old and older met both aerobic and muscle
      strengthening guidelines, compared with 15.2% of those 18 to 64 years old (P <
      0.05). The most common activity reported for ages 18 to 64 years was walking
      (53.3%), followed by running (12.7%), and gardening (4.7%). Among adults aged 65
      and older, the top three activities were walking (63.2%), gardening (13.3%), and
      use of a bicycle machine (2.9%). The activity intensity was significantly greater
      for walking, gardening, and household activities among older adults compared with
      those younger than age 65. CONCLUSIONS: Because the recommended levels of
      physical activity are not met by a majority of Alabama residents, it is important
      to incorporate this information into state cancer objectives. Older adults may
      have higher relative energy costs compared with younger adults. Future studies
      should discern whether activities previously classified as low intensity have
      adequate health benefits, especially for cancer survivors and older adults with
      comorbidities.

PMID- 25972219
TI  - Assessment of appropriate antibiotic prescribing for urinary tract infections in
      an internal medicine clinic.
AB  - OBJECTIVES: Urinary tract infections (UTIs) are one of the most common infections
      encountered in ambulatory care and inpatient settings. Although these infections
      are common, not all patients are prescribed an appropriate antibiotic or duration
      of therapy. The primary objective of this analysis was to evaluate the
      appropriateness of antibiotic selection and duration of therapy for patients in
      an adult internal medicine clinic diagnosed as having a UTI. METHODS: We
      conducted a retrospective chart review (July 1, 2012-June 30, 2013) of adult
      patients in an internal medicine clinic who were diagnosed as having a UTI.
      Pediatric and pregnant patients were excluded from the analysis. Data pertaining
      to the classification of UTI, antibiotic regimen, urine culture, and renal
      function were collected. All of the data were analyzed to determine whether the
      prescribing habits at the internal medicine clinic aligned with Infectious
      Diseases Society of America (IDSA) guidelines for antibiotic selection and
      duration of therapy for acute uncomplicated cystitis, complicated cystitis,
      catheter-associated UTI, and pyelonephritis. RESULTS: There were 269 records
      available for the analysis, with the majority of the cases being uncomplicated
      and complicated UTIs. Of 128 cases of patients with uncomplicated UTIs and 116
      cases of patients with complicated UTIs, 64.1% and 42.2%, respectively, were
      prescribed appropriate first- or second-line therapy, which aligned with the
      recommendations of the IDSA. Regarding the individual components of the UTI
      treatment regimen, antibiotic selection had the highest frequency of
      appropriateness, with 97.6% of uncomplicated UTI cases and 90.5% of complicated
      UTI cases having been treated with a recommended antibiotic. In contrast, the
      treatment duration for uncomplicated and complicated UTIs had the lowest
      frequency of appropriateness, at 71.9% and 58.6%, respectively. CONCLUSIONS:
      Receiving an adequate antibiotic regimen for a UTI is important to prevent
      treatment failure and the emergence of resistant organisms. Overall, the studied
      antibiotic regimens prescribed for various UTIs diagnosed in the clinic did not
      align with the IDSA recommendations.

PMID- 25972220
TI  - Anatomical basis for the development of a thoracic duct cannulation model without
      thoracotomy in Large White pigs.
AB  - BACKGROUND: To collect lymph draining the lungs provides a useful strategy for
      tracing pulmonary microvascular fluid and protein biology. A methodology that
      allows for in vivo sampling of efferent pulmonary lymph in real-time in sheep by
      cannulating the thoracic duct without entering the thoracic cavity was previously
      established. To develop a similar thoracic duct cannulation model without
      thoracotomy in pigs, we investigated the anatomy of the left cervico-thoracic
      regions of 15 Large White (Yorkshire or Yorkshire-dominated) piglets (aged 4-7
      weeks). RESULTS: The thoracic duct, together with the left tracheal trunk, joined
      the cardiovascular system (the ampulla of the thoracic duct) at a site located
      craniomedial to the first rib on the left in 80 % (12/15) of the piglets.
      CONCLUSIONS: As the location of the ampulla of the thoracic duct was consistent
      in most of the piglets, Large White piglets appear to be suitable for the
      development of a thoracic duct cannulation model without thoracotomy. The
      anatomical findings in this study will enable the development of further surgical
      procedures for cannulating the thoracic duct without thoracotomy, with minimal
      damage to local tissue, and without transecting any major blood vessels, nerves
      or muscle bellies. The establishment of a thoracic duct cannulation model for
      collecting in vivo, in situ efferent lymph, including pulmonary lymph, in pigs
      without entering the thoracic cavity would be invaluable for many immunological
      studies, studies on pulmonary immune responses in particular.

PMID- 25972221
TI  - The husband's story: from tragedy to learning and action.

PMID- 25972222
TI  - What are patients' care experience priorities?

PMID- 25972223
TI  - Patient and carer identified factors which contribute to safety incidents in
      primary care: a qualitative study.
AB  - BACKGROUND: Patients can have an important role in reducing harm in primary-care
      settings. Learning from patient experience and feedback could improve patient
      safety. Evidence that captures patients' views of the various contributory
      factors to creating safe primary care is largely absent. The aim of this study
      was to address this evidence gap. METHODS: Four focus groups and eight
      semistructured interviews were conducted with 34 patients and carers from south
      east Australia. Participants were asked to describe their experiences of primary
      care. Audio recordings were transcribed verbatim and specific factors that
      contribute to safety incidents were identified in the analysis using the
      Yorkshire Contributory Factors Framework (YCFF). Other factors emerging from the
      data were also ascertained and added to the analytical framework. RESULTS:
      Thirteen factors that contribute to safety incidents in primary care were
      ascertained. Five unique factors for the primary-care setting were discovered in
      conjunction with eight factors present in the YCFF from hospital settings. The
      five unique primary care contributing factors to safety incidents represented a
      range of levels within the primary-care system from local working conditions to
      the upstream organisational level and the external policy context. The 13 factors
      included communication, access, patient factors, external policy context, dignity
      and respect, primary-secondary interface, continuity of care, task performance,
      task characteristics, time in the consultation, safety culture, team factors and
      the physical environment. DISCUSSION: Patient and carer feedback of this type
      could help primary-care professionals better understand and identify potential
      safety concerns and make appropriate service improvements. The comprehensive
      range of factors identified provides the groundwork for developing tools that
      systematically capture the multiple contributory factors to patient safety.

PMID- 25972224
TI  - Use of MALDI Biotyper plus ClinProTools mass spectra analysis for correct
      identification of Streptococcus pneumoniae and Streptococcus mitis/oralis.
AB  - BACKGROUND: Differentiation of Streptococcus pneumoniae from other viridans group
      streptococci is well known to be challenging in clinical laboratories. Matrix
      assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF
      MS) had been reported to be a good alternative for Streptococcus species level
      identification. However, differentiation of S. pneumoniae from other
      Streptococcus mitis group organisms was found to be problematic using the Bruker
      MALDI Biotyper system. METHODS: This study used the Bruker MALDI Biotyper system
      in addition to a mass spectra model analysis generated by 10 reference strains of
      S. pneumoniae, 8 strains of S. mitis and 2 strains of S. oralis in the
      ClinProTools to identify 28 clinical isolates of S. pneumoniae and 47 isolates of
      S. mitis/oralis. The results were compared with those generated by the MALDI
      Biotyper system alone. RESULTS: The percentages of correct species level
      identification using the MALDI Biotyper system alone and the direct transfer and
      extraction method were 66.7% (50/75) and 70.7% (53/75), respectively. With the
      additional ClinProTools mass spectra analysis, the percentages of correct
      identification by the direct transfer and extraction method increased to 85.3%
      (64/75) and 100% (75/75), respectively. This new workflow significantly improved
      the accuracy of S. pneumoniae and S. mitis/oralis identification. CONCLUSIONS:
      The additional ClinProTools mass spectra analysis with extraction method after
      MALDI Biotyper identification significantly improved the accuracy of
      identification among S. pneumoniae, S. oralis and S. mitis. The extra 15 min
      processing time of spectra analysis should be affordable in most clinical
      laboratories. We suggest that the same approach could be further explored in
      handling other bacterial species with high similarities.

PMID- 25972225
TI  - Spleen injury following left extracorporeal shockwave lithotripsy (ESWL).
AB  - BACKGROUND: A splenic rupture associated with extracorporeal shockwave
      lithotripsy (ESWL) is exceedingly rare. We report a case of stage 3 splenic
      laceration, hemoperitoneum and subsequent splenic rupture following an ESWL for a
      left mid polar renal calculus. CASE PRESENTATION: During the ESWL, although the
      patient's pain was controlled the gentleman was very nervous and had to be
      repositioned eight individual times. Approximately 6 hours after the ESWL, the
      patient phoned the urologist complaining of severe left flank pain unlike any
      previous episode of renal colic. A computerized tomography (CT) scan demonstrated
      a stage 3 splenic injury with hemoperitoneum. The patient decompensated and an
      emergent splenectomy was then performed and the patient experienced an uneventful
      recovery. CONCLUSIONS: Splenic injury likely results from unintentional movement
      during the sound wave administration for the stone fragmentation procedure.
      Utilizing noise cancelling headphones during ESWL may preclude the potential
      pitfalls of patient nervousness.

PMID- 25972227
TI  - Electrochemical fabrication of nanoporous copper films in choline chloride-urea
      deep eutectic solvent.
AB  - Nanoporous copper films were fabricated by a facile electrochemical
      alloying/dealloying process without the need of a template. A deep eutectic
      solvent made from choline chloride (ChCl) and urea was used with zinc oxide as
      the metal salt. Cyclic voltammetry was used to characterise the electrochemical
      reduction of zinc and follow Cu-Zn alloy formation on the copper substrate at
      elevated temperatures from 353 to 393 K. The alloy formation was confirmed by X
      ray diffraction spectra. 3D, open and bicontinuous nanoporous copper films were
      obtained by in situ electrochemically etching (dealloying) of the zinc component
      in the Cu-Zn surface alloys at an appropriate potential (-0.4 V vs. Ag). This
      dealloying process was found to be highly temperature dependent and surface
      diffusion controlled, which involved the self-assembly of copper atoms at the
      alloy/electrolyte interface. Additionally, the effects of the deposition
      parameters, including deposition temperature, current density as well as total
      charge density on resulting the microstructure were investigated by scanning
      electron microscopy, and atomic force microscope. 

PMID- 25972226
TI  - Integrating mHealth in Oncology: Experience in the Province of Trento.
AB  - BACKGROUND: The potential benefits of the introduction of electronic and mobile
      health (mHealth) information technologies, to support the safe delivery of
      intravenous chemotherapy or oral anticancer therapies, could be exponential in
      the context of a highly integrated computerized system. OBJECTIVE: Here we
      describe a safe therapy mobile (STM) system for the safe delivery of intravenous
      chemotherapy, and a home monitoring system for monitoring and managing toxicity
      and improving adherence in patients receiving oral anticancer therapies at home.
      METHODS: The STM system is fully integrated with the electronic oncological
      patient record. After the prescription of chemotherapy, specific barcodes are
      automatically associated with the patient and each drug, and a bedside barcode
      reader checks the patient, nurse, infusion bag, and drug sequence in order to
      trace the entire administration process, which is then entered in the patient's
      record. The usability and acceptability of the system was investigated by means
      of a modified questionnaire administered to nurses. The home monitoring system
      consists of a mobile phone or tablet diary app, which allows patients to record
      their state of health, the medications taken, their side effects, and a Web
      dashboard that allows health professionals to check the patient data and monitor
      toxicity and treatment adherence. A built-in rule-based alarm module notifies
      health care professionals of critical conditions. Initially developed for chronic
      patients, the system has been subsequently customized in order to monitor home
      treatments with capecitabine or sunitinib in cancer patients (Onco-TreC).
      RESULTS: The STM system never failed to match the patient/nurse/drug sequence
      association correctly, and proved to be accurate and reliable in tracing and
      recording the entire administration process. The questionnaires revealed that the
      users were generally satisfied and had a positive perception of the system's
      usefulness and ease of use, and the quality of their working lives. The pilot
      studies with the home monitoring system with 43 chronic patients have shown that
      the approach is reliable and useful for clinicians and patients, but it is also
      necessary to pay attention to the expectations that mHealth solutions may raise
      in users. The Onco-TreC version has been successfully laboratory tested, and is
      now ready for validation. CONCLUSIONS: The STM and Onco-TreC systems are fully
      integrated with our complex and composite information system, which guarantees
      privacy, security, interoperability, and real-time communications between
      patients and health professionals. They need to be validated in order to confirm
      their positive contribution to the safer administration of anticancer drugs.

PMID- 25972228
TI  - Examining DSM criteria for trichotillomania in a dimensional framework:
      implications for DSM-5 and diagnostic practice.
AB  - BACKGROUND: Diagnosis of trichotillomania (TTM) requires meeting several criteria
      that aim to embody the core pathology of the disorder. These criteria are
      traditionally interpreted monothetically, in that they are all equally necessary
      for diagnosis. Alternatively, a dimensional conceptualization of psychopathology
      allows for examination of the relatedness of each criterion to the TTM latent
      continuum. OBJECTIVES: First, to examine the ability of recently removed criteria
      (B and C) to identify the latent dimensions of TTM psychopathology, such that
      they discriminate between individuals with low and high degrees of hair pulling
      severity. Second, to determine the impact of removing criteria B and C on the
      information content of remaining diagnostic criteria. Third, to determine the
      psychometric properties of remaining TTM diagnostic criteria that remain largely
      unchanged in DSM-5; that is, whether they measure distinct or overlapping levels
      of TTM psychopathology. Fourth, to determine whether information content derived
      from diagnostic criteria aid in the prediction of disease trajectory (i.e., can
      relapse propensity be predicted from criteria endorsement patterns). METHOD:
      Statistics derived from item response theory were used to examine diagnostic
      criteria endorsement in 91 adults with TTM who underwent psychotherapy. RESULTS:
      The removal of two criteria in DSM-5 and psychometric validity of remaining
      criteria was supported. Additionally, individual trait parameters were used to
      predict treatment progress, uncovering predictive power where none previously
      existed. CONCLUSIONS: Diagnostic criteria for TTM should be examined in
      dimensional models, which allow for nuanced and sensitive measurement of core
      symptomology in treatment contexts.

PMID- 25972229
TI  - The effect of meteorological parameters on the number of renal colic patients.
AB  - In this study, we investigated the effect of meteorological parameters on the
      number of renal colic patients who admitted to the emergency department regarding
      patients' gender, patients' age and season. Patients who were admitted to the
      emergency department with renal colic during a year were studied retrospectively.
      The number of patients admitted daily was divided into groups according to
      gender, age and seasons, and correlations between the daily meteorological
      parameters were examined. In our study, a total of 1890 patients were enrolled
      and of those 64.9% (n=1227) were male. The mean age of the patients was 38+/
      14.7/years (18-94). The number of patients admitted daily was 5+/-2.9/patients (1
      18). Positive correlation was found between the daily number of patients and
      daily maximum temperature (p<0.001, r=0.212), and daily minimum temperature
      (p=0.003, r=0.160) and daily temperature difference (p<0.001, r=0.218).
      Additionally, a negative correlation with the daily relative humidity (p=0.001,
      r=-0.169) was detected. As a result of multivariate regression analysis, age was
      found to independently affect the number of RC patients admitted to the emergency
      department (R2 0.0079, t -3.56, p<0.001). Negative correlation was found between
      relative humidity and female patients, patients in the 30-39 years of age group,
      and the daily number of RC patients admitted in spring. We found positive
      correlation between temperature and the number of patients under the age of 39
      years, but we concluded that the daily number of patients above the age of 40
      years did not significantly correlate with temperature rise. In our study, we
      determined that meteorological parameters have an effect on renal colic and that
      this effect varies depending on the patients' age, patients' gender and season.

PMID- 25972231
TI  - Oncostatin M is a potential agent for the treatment of obesity and related
      metabolic disorders: a study in mice.
AB  - AIMS/HYPOTHESIS: Obesity and insulin resistance are closely associated with
      adipose tissue dysfunction caused by the abnormal recruitment of inflammatory
      cells, including macrophages. Oncostatin M (OSM), a member of the IL-6 family of
      cytokines, plays important roles in a variety of biological functions including
      the regulation of inflammatory responses. In previous reports, we have
      demonstrated that mice deficient in the OSM receptor beta subunit show obesity,
      adipose tissue inflammation, insulin resistance and hepatic steatosis, all of
      which are exacerbated by feeding the mice a high-fat diet. These results prompted
      us to test the therapeutic effects of OSM on obesity-induced metabolic disorders
      using mouse models of obesity. METHODS: In diet-induced obese and ob/ob mice,
      metabolic variables were assessed physiologically, histologically and
      biochemically after the intraperitoneal injection of recombinant mouse OSM twice
      a day for 1 week. RESULTS: Treatment with OSM improved obesity, adipose tissue
      inflammation, insulin resistance and hepatic steatosis in both mouse models.
      Although OSM reduced food intake, such therapeutic effects of OSM were observed
      even under pair-feeding conditions. Functionally, OSM directly changed the
      phenotype of adipose tissue macrophages from M1 type (inflammatory) to M2 type
      (anti-inflammatory). In the liver, OSM suppressed the expression of genes related
      to fatty acid synthesis and increased the expression of genes related to fatty
      acid oxidation. Furthermore, OSM decreased lipid absorption and increased the
      expression of active glucagon-like peptide-1 in the intestine.
      CONCLUSIONS/INTERPRETATION: We showed that OSM is a novel candidate to act as a
      powerful therapeutic agent for the treatment of obesity-induced metabolic
      disorders.

PMID- 25972233
TI  - Screening Criteria in Breast Cancer Trials: Are They Too Restrictive?

PMID- 25972232
TI  - All-cause mortality in a nationwide cohort of childhood-onset diabetes in Norway
      1973-2013.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the association between all
      cause mortality and sex, age at diagnosis and year of diagnosis in Norwegian
      patients with childhood-onset diabetes. METHODS: The study was based on the
      nationwide, population-based Norwegian Childhood Diabetes Registry, which
      includes all newly diagnosed cases of childhood-onset diabetes at age 0-14 years
      in 1973-1982 and 1989-2012 (n = 7,884). Patients were followed until date of
      death, emigration or 30 September 2013. RESULTS: Among the 7,884 patients,
      representing 132,420 person-years, 249 (3.2%) died during a mean follow-up of
      16.8 (range 0.0-40.7) years. The standardised mortality ratio (SMR) for the total
      cohort was 3.6 (95% CI 3.1, 4.0), increasing by attained age. Absolute mortality
      was significantly lower in females than in males (HR 0.50 [95% CI 0.38, 0.65]),
      although the SMRs were similar. Cox regression analysis showed a significant
      decrease in mortality of 49% (HR 0.51 [95% CI 0.28, 0.93]) for those diagnosed in
      1999-2012 compared with those diagnosed in 1973-1982 (p = 0.03).
      CONCLUSIONS/INTERPRETATION: In spite of improved diabetes care, mortality is
      still three to four times higher in those with childhood-onset diabetes compared
      with the general population in Norway. However, absolute mortality has declined
      among children diagnosed most recently (1999-2012) compared with those diagnosed
      in the earliest period (1973-1982).

PMID- 25972234
TI  - Multivariate and geo-spatial approach for seawater quality of Chidiyatappu Bay,
      south Andaman Islands, India.
AB  - Chidiyatappu Bay is one of the least disturbed marine environments of Andaman &
      Nicobar Islands, the union territory of India. Oceanic flushing from southeast
      and northwest direction is prevalent in this bay. Further, anthropogenic activity
      is minimal in the adjoining environment. Considering the pristine nature of this
      bay, seawater samples collected from 12 sampling stations covering three seasons
      were analyzed. Principal Component Analysis (PCA) revealed 69.9% of total
      variance and exhibited strong factor loading for nitrite, chlorophyll a and
      phaeophytin. In addition, analysis of variance (ANOVA-one way), regression
      analysis, box-whisker plots and Geographical Information System based hot spot
      analysis further simplified and supported multivariate results. The results
      obtained are important to establish reference conditions for comparative study
      with other similar ecosystems in the region. 

PMID- 25972235
TI  - Cost-Effectiveness of School-Based Prevention of Cannabis Use.
AB  - BACKGROUND: Cannabis is the most frequently used illicit drug globally. Despite
      increasing evidence that cannabis use is associated with adverse health effects,
      the knowledge on preventative strategies is still limited. This study stemmed
      from a systematic review of effective prevention in which school-based programmes
      were identified as promising. The primary objective was to evaluate the cost
      effectiveness of Project ALERT (Adolescent, Learning, Experiences, Resistance,
      and Training), compared with ordinary ATOD (Alcohol, Tobacco, and Other Drug)
      education, among Swedish students in the eighth grade of compulsory school.
      METHODS: The cost-effectiveness analysis was performed from the societal
      perspective with quality-adjusted life-years (QALYs) as an outcome (willingness
      to-pay threshold ?50,000) and follow-up periods from 1 year to a lifetime,
      considering a discounting rate of 3%, and with costs inflated to 2013 levels. A
      Markov model was constructed on the basis of the 'states' of single use, regular
      use, daily use and use of other illicit drugs, which were associated with
      'complications' of psychosis, schizophrenia, traffic accidents, depression and
      amotivational syndrome. Health and cost consequences were linked to both states
      and complications. RESULTS: The programme was cost saving on the basis of
      evidence from the USA (ratio 1:1.1), and was cost effective (incremental cost
      effectiveness ratio ?22,384 per QALY) after reasonable adjustment for the Swedish
      context and with 20 years of follow-up. When the target group was restricted to
      boys who were neither studying nor working/doing work experience, the programme
      was cost effective after 9 years and cost saving (ratio 1:3.2) after 20 years.
      CONCLUSION: School-based prevention such as Project ALERT has the potential to be
      cost effective and to be cost saving if implemented in deprived areas. In the
      light of the shifting landscape regarding legalization of cannabis, it seems
      rational to continue the health economic analysis of prevention initiated here.

PMID- 25972230
TI  - Prospective association of a genetic risk score and lifestyle intervention with
      cardiovascular morbidity and mortality among individuals with type 2 diabetes:
      the Look AHEAD randomised controlled trial.
AB  - AIMS/HYPOTHESIS: Both obesity and genetics contribute to cardiovascular disease
      (CVD). We examined whether a genetic risk score (GRS) prospectively predicted
      cardiovascular morbidity and mortality among overweight/obese individuals with
      type 2 diabetes and whether behavioural weight loss could diminish this
      association. METHODS: Look AHEAD (Action for Health in Diabetes) is a randomised
      controlled trial to determine the effects of intensive lifestyle intervention
      (ILI), including weight loss and physical activity, relative to diabetes support
      and education, on cardiovascular outcomes among overweight/obese individuals with
      type 2 diabetes. Of the participants, 4,016 provided consent for genetic analyses
      and had DNA samples passing quality control procedures. These secondary data
      analyses focused on whether a GRS derived from 153 single nucleotide
      polymorphisms (SNPs) associated with coronary artery disease in the most recent
      genome-wide association study predicted cardiovascular morbidity and mortality
      over a median of 9.6 years of follow-up, and whether ILI would diminish this
      association. RESULTS: The GRS significantly predicted the primary composite
      endpoint of death from cardiovascular causes, nonfatal myocardial infarction,
      nonfatal stroke, or hospitalisation for angina in the full sample (HR, 95% CI per
      1 SD increase in GRS: 1.19 [1.10, 1.28]) and among individuals with no known
      history of CVD at baseline (HR 1.18 [95% CI 1.07, 1.30]). In no case did ILI
      significantly alter this association. CONCLUSIONS/INTERPRETATION: A GRS comprised
      of SNPs significantly predicts cardiovascular morbidity and mortality over 9.6
      years of follow-up in Look AHEAD. Lifestyle intervention did not alter the
      genetic association. CLINICAL TRIAL REGISTRATION: NCT00017953; NCT01270763.

PMID- 25972236
TI  - Kidney disease in heart failure: the importance of novel biomarkers for type 1
      cardio-renal syndrome detection.
AB  - Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an
      independent risk factor for adverse outcome, although the most important clinical
      trials tend to exclude patients with moderate and severe renal insufficiency.
      Despite this common association, the precise pathophysiological connection and
      liaison between heart and kidney is partially understood. Moreover, is it not
      enough considering how much cardio-renal syndrome type 1 is attributable to
      previous CKD, and how much to new-onset acute kidney injury (AKI). Neither
      development of AKI, its progression and time nor duration is related to an
      adverse outcome. An AKI definition is not universally recognized, and many
      confounding terms have been used in literature: "worsening renal function",
      "renal impairment", "renal dysfunction", etc., are all names that contribute to
      misunderstanding, and do not facilitate an universal classification. Therefore,
      AKI development should be the consequence of the basal clinical characteristics
      of patients, different primitive kidney disease and hemodynamic status. AKI could
      also be the mirror of several underlying associated diseases poorly controlled.
      Finally, it is not clear which is the optimal laboratory tool for identifying
      patients with an increased risk of AKI. In the current report, we review the
      different kidney diseases' impact in HF, and we analyze the modalities for AKI
      recognition during HF focusing our attention about some new biomarkers with
      potential application in the current setting. 

PMID- 25972238
TI  - Hyperglycemia and Mortality Risk in Patients with Primary Intracerebral
      Hemorrhage: A Meta-Analysis.
AB  - Hyperglycemia may be associated with worse functional outcomes in patients with
      primary intracerebral hemorrhage. We performed a systematic review and meta
      analysis to investigate the relationship between hyperglycemia and mortality risk
      in patients with primary intracerebral hemorrhage. We searched PubMed and Embase
      databases for studies investigating the association between hyperglycemia and
      mortality risk in patients with primary intracerebral hemorrhage. We estimated
      the pooled relative risk (RR) with its 95% confidence interval (95% CI) to assess
      the impact of hyperglycemia on mortality risk. Seventeen studies with a total of
      6527 primary intracerebral hemorrhage patients were included. Meta-analysis of
      those studies showed that hyperglycemia significantly increased risk of mortality
      in patients with primary intracerebral hemorrhage (RR = 2.36, 95% CI 1.79-3.12).
      Subgroup analysis by time of follow-up showed that hyperglycemia significantly
      increased risk of short-term mortality (RR = 3.97, 95% CI 2.13-7.43) and long
      term mortality (RR = 1.53, 95% CI 1.14-2.05). The RR of mortality for per 1
      mmol/L increment in glucose level was 1.14 (95% CI 1.06-1.22). In patients with
      primary intracerebral hemorrhage, hyperglycemia significantly increases risk of
      both short-term mortality and long-term mortality.

PMID- 25972237
TI  - Treatment with Trehalose Prevents Behavioral and Neurochemical Deficits Produced
      in an AAV alpha-Synuclein Rat Model of Parkinson's Disease.
AB  - The accumulation of misfolded alpha-synuclein in dopamine (DA) neurons is
      believed to be of major importance in the pathogenesis of Parkinson's disease
      (PD). Animal models of PD, based on viral-vector-mediated over-expression of
      alpha-synuclein, have been developed and show evidence of dopaminergic toxicity,
      providing us a good tool to investigate potential therapies to interfere with
      alpha-synuclein-mediated pathology. An efficient disease-modifying therapeutic
      molecule should be able to interfere with the neurotoxicity of alpha-synuclein
      aggregation. Our study highlighted the ability of an autophagy enhancer,
      trehalose (at concentrations of 5 and 2% in drinking water), to protect against
      A53T alpha-synuclein-mediated DA degeneration in an adeno-associated virus
      serotype 1/2 (AAV1/2)-based rat model of PD. Behavioral tests and neurochemical
      analysis demonstrated a significant attenuation in alpha-synuclein-mediated
      deficits in motor asymmetry and DA neurodegeneration including impaired DA
      neuronal survival and DA turnover, as well as alpha-synuclein accumulation and
      aggregation in the nigrostriatal system by commencing 5 and 2% trehalose at the
      same time as delivery of AAV. Trehalose (0.5%) was ineffective on the above
      behavioral and neurochemical deficits. Further investigation showed that
      trehalose enhanced autophagy in the striatum by increasing formation of LC3-II.
      This study supports the concept of using trehalose as a novel therapeutic
      strategy that might prevent/reverse alpha-synuclein aggregation for the treatment
      of PD.

PMID- 25972239
TI  - Chitooligosaccharide Inhibits Scar Formation and Enhances Functional Recovery in
      a Mouse Model of Sciatic Nerve Injury.
AB  - Chitooligosaccharide (COS) has been shown to induce fibroblast apoptosis,
      indicating that it could be used as a material to inhibit scar formation. In the
      present study, we used a mouse model of sciatic nerve injury (SNI) to determine
      the role of COS in scar inhibition and functional recovery. The animals were
      divided into three groups: SNI, SNI + vehicle, and SNI + COS group. We performed
      a series of functional and histological examinations at ctrl, 0 min, 14 days, and
      42 days, including behavioral recovery, percentage of regenerating axons, degree
      of scar formation, vascular changes, type I and type III collagen ratio, and
      percentage of demyelinated axons. The SNI + COS group exhibited better recovery
      of sensory and motor function and less scar formation. Two-photon microscopy
      showed that the percentage of regenerating axons was highest in the SNI + COS
      group at 14 and 42 days. Our results suggested that COS can inhibit scar
      formation and enhance functional recovery by inducing fibroblast death, altering
      the proportion of different vascular diameters, changing the ratio of type I/type
      III collagen, and reducing the percentage of demyelinated axons. COS might be a
      useful drug in the treatment of SNI to reduce scar formation, but additional
      research is required to clarify the relevant molecular pathways.

PMID- 25972240
TI  - Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF
      1a in a Spinal Cord Injury Model.
AB  - Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine
      with multiple functions in the brain during development and in adulthood. The
      inflammatory response initiated by spinal cord injury (SCI) involves the
      processing of interleukin-1beta (IL-1beta) and IL-18 mediated by caspase-1 which
      is under the control of an intracellular multiprotein complex termed
      inflammasome. Using an SCI rat model, we found improved functional long-term
      recovery which is paralleled by a reduction of apoptosis after intrathecal
      treatment with SDF-1a. An intriguing aspect is that SDF-1a changed the number of
      neuroinflammatory cells in the damaged area. We further examined the cellular
      localization and sequential expression of several inflammasomes during SCI at 6
      h, 24 h, 3 days, and 7 days as well as the role of SDF-1a as a regulatory factor
      for inflammasomes. Using 14-week old male Wistar rats, spinal cord contusion was
      applied at the thoracic segment 9, and animals were subsequently treated with SDF
      1a via intrathecal application through an osmotic pump. SCI temporally increased
      the expression of the inflammasomes NLRP3, ASC, the inflammatory marker tumor
      necrosis factor-a (TNF-a), interleukin-1beta (IL-1beta) and IL-18. SDF-1a
      significantly reduced the levels of IL-18, IL-1b, TNF-a, NLRP3, ASC, and caspase
      1. Immunofluorescence double-labeling demonstrated that microglia and neurons are
      major sources of the ASC and NLRP3 respectivley. Our data provide clear evidence
      that SCI stimulates a complex scenario of inflammasome activation at the injured
      site and that SDF-1a-mediated neuroprotection presumably depends on the
      attenuation of the inflammasome complex.

PMID- 25972241
TI  - Complement Peptide C3a Promotes Astrocyte Survival in Response to Ischemic
      Stress.
AB  - Astrocytes are the most numerous cells in the central nervous system with a range
      of homeostatic and regulatory functions. Under normal conditions as well as after
      ischemia, astrocytes promote neuronal survival. We have previously reported that
      the complement-derived peptide C3a stimulates neuronal differentiation of neural
      progenitor cells and protects the immature brain tissue against hypoxic-ischemic
      injury. Here, we studied the effects of C3a on the response of mouse cortical
      astrocytes to ischemia. We have found that chemical ischemia, induced by combined
      inhibition of oxidative phosphorylation and glycolysis, upregulates the
      expression of C3a receptor in cultured primary astrocytes. C3a treatment
      protected wild-type but not C3a receptor-deficient astrocytes from cell death
      induced by chemical ischemia or oxygen-glucose deprivation by reducing ERK
      signaling and caspase-3 activation. C3a attenuated ischemia-induced upregulation
      of glial fibrillary acidic protein; however, the protective effects of C3a were
      not dependent on the presence of the astrocyte intermediate filament system. Pre
      treatment of astrocytes with C3a during recovery abrogated the ischemia-induced
      neuroprotective phenotype of astrocytes. Jointly, these results provide the first
      evidence that the complement peptide C3a modulates the response of astrocytes to
      ischemia and increases their ability to cope with ischemic stress.

PMID- 25972243
TI  - Carfilzomib is an effective anticancer agent in anaplastic thyroid cancer.
AB  - Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies.
      Currently, there is no standard or effective therapy for ATC. Drug repurposing
      for cancer treatment is an emerging approach for identifying compounds that may
      have antineoplastic effects. The aim of this study was to use high-throughput
      drug library screening to identify and subsequently validate novel therapeutic
      agents with anticancer effects in ATC. We performed quantitative high-throughput
      screening (qHTS) in ATC cell lines (SW-1736, 8505C, and C-643), using a compound
      library of 3282 drugs. qHTS identified 100 compounds that were active in all
      three ATC cell lines. Proteasome inhibitors were one of the most active drug
      categories according to enrichment analysis. Of the three proteasome inhibitors
      screened, a second-generation proteasome inhibitor, carfilzomib, was the most
      active. Treatment of ATC cells with carfilzomib significantly inhibited cellular
      proliferation and induced G2/M cell cycle arrest and caspase-dependent apoptosis.
      Mechanistically, carfilzomib increased expression of p27 (CDKN1B) and decreased
      expression of the anti-apoptotic protein ATF4. Pretreatment with carfilzomib
      reduced in vivo metastases (lung, bone, liver, and kidney) and disease
      progression, and decreased N-cadherin expression. Carfilzomib treatment of mice
      with established, widely metastatic disease significantly increased their
      survival, without significant toxicity. Our findings support the use or clinical
      study of carfilzomib as a therapeutic option in patients with advanced and
      metastatic ATC. 

PMID- 25972242
TI  - Expression of ERG protein in prostate cancer: variability and biological
      correlates.
AB  - Prostate cancer is the second leading cause of cancer-related death of men in the
      USA. The TMPRSS2/ERG (T/E) fusion gene is present in approximately 50% of
      prostate cancers and promotes tumor progression in vivo. The presence of the T/E
      fusion gene is strongly associated with the expression of ERG protein, but
      emerging evidence indicates a significant interfocal and intrafocal variability
      in the levels of ERG protein expression. We therefore analyzed ERG protein
      expression by image analysis to objectively quantitate the extent of such
      heterogeneity, and confirmed significant interfocal and intrafocal variability of
      ERG protein expression levels in cancer expressing ERG. To define the pathways
      associated with ERG and its variable expression in prostate cancer, we have
      analyzed the correlations of ERG expression, as evaluated by
      immunohistochemistry, with 46 key proteins associated with signal transduction,
      transcriptional control, and other processes using a large tissue microarray with
      more than 500 prostate cancers. We found a significant correlation of ERG
      expression with the markers of activation of the PI3K, MYC, and NFkappaB
      pathways, which had previously been linked directly or indirectly to ERG
      expression. We have also identified significant correlations with novel proteins
      that have not been previously linked to ERG expression, including serum response
      factor, the p160 coactivator SRC1, and Sprouty1. Notably, SKP2 only correlated
      with a high level of ERG protein expression. Thus ERG expression is variable in
      prostate cancer and is associated with activation of multiple pathways and
      proteins including several potentially targetable pathways. 

PMID- 25972244
TI  - S6 kinase signaling: tamoxifen response and prognostic indication in two breast
      cancer cohorts.
AB  - Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen
      receptor (ER) pathways may be a future clinical tool for the prediction of
      adjuvant treatment response in primary breast cancer. Using immunohistological
      staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and
      2 as biomarkers for tamoxifen benefit in two independent clinical trials
      comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of
      tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated.
      We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic
      AKT activity, whereas high protein expression levels of S6K2 and phosphorylated
      (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT
      s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a
      reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84),
      compared with a significant benefit from tamoxifen treatment in patients without
      tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, P<0.00001). Also
      S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with
      low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition,
      high protein expression of S6K1, independent of localization, predicted worse
      prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus).
      In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with
      proliferation and response to tamoxifen. Monitoring their activity and
      intracellular localization may provide biomarkers for breast cancer treatment,
      allowing the identification of a group of patients less likely to benefit from
      tamoxifen and thus in need of an alternative or additional targeted treatment. 

PMID- 25972245
TI  - Structural and functional consequences of succinate dehydrogenase subunit B
      mutations.
AB  - Mitochondrial dysfunction, due to mutations of the gene encoding succinate
      dehydrogenase (SDH), has been implicated in the development of adrenal
      phaeochromocytomas, sympathetic and parasympathetic paragangliomas, renal cell
      carcinomas, gastrointestinal stromal tumours and more recently pituitary tumours.
      Underlying mechanisms behind germline SDH subunit B (SDHB) mutations and their
      associated risk of disease are not clear. To investigate genotype-phenotype
      correlation of SDH subunit B (SDHB) variants, a homology model for human SDH was
      developed from a crystallographic structure. SDHB mutations were mapped, and
      biochemical effects of these mutations were predicted in silico. Results of
      structural modelling indicated that many mutations within SDHB are predicted to
      cause either failure of functional SDHB expression (p.Arg27*, p.Arg90*, c.88delC
      and c.311delAinsGG), or disruption of the electron path (p.Cys101Tyr, p.Pro197Arg
      and p.Arg242His). GFP-tagged WT SDHB and mutant SDHB constructs were transfected
      (HEK293) to determine biological outcomes of these mutants in vitro. According to
      in silico predictions, specific SDHB mutations resulted in impaired mitochondrial
      localisation and/or SDH enzymatic activity. These results indicated strong
      genotype-functional correlation for SDHB variants. This study reveals new
      insights into the effects of SDHB mutations and the power of structural modelling
      in predicting biological consequences. We predict that our functional assessment
      of SDHB mutations will serve to better define specific consequences for SDH
      activity as well as to provide a much needed assay to distinguish pathogenic
      mutations from benign variants. 

PMID- 25972246
TI  - Pulmonary cowpox in cats: five cases.
AB  - CASE SERIES SUMMARY: This case series documents five cases of pneumonia (with
      pleural effusion in three cases) caused by cowpox virus (CPxV) in domestic cats.
      Predisposition to pneumonia may have resulted from mixed infections in two cases
      (feline herpesvirus and Bordetella bronchiseptica in one cat, and Mycoplasma
      species in the other). RELEVANCE AND NOVEL INFORMATION: As well as diagnostic
      confirmation by previously described methods of virus isolation from skin
      lesions, and demonstration of pox virions in skin samples using electron
      microscopy and inclusion bodies in histological preparations, this is the first
      report of diagnosis by virus isolation from bronchoalveolar lavage fluid or
      pleural fluid, and demonstration of inclusion bodies in cytological preparations.
      This is also the first series to report treatment with interferon omega (IFN
      omega). Two cats survived, both of which had been treated with IFN-omega. As CPxV
      represents a serious zoonotic risk it is an important differential diagnosis of
      pneumonia in cats.

PMID- 25972247
TI  - Systematic review of the behavioural assessment of pain in cats.
AB  - OBJECTIVES: The objectives were to review systematically the range of assessment
      tools used in cats to detect the behavioural expression of pain and the evidence
      of their quality; and to examine behavioural metrics (considering both the
      sensory and affective domains) used to assess pain. METHODS: A search of PubMed
      and ScienceDirect, alongside articles known to the authors, from 2000 onwards,
      for papers in English was performed. This was followed by a manual search of the
      references within the primary data sources. Only peer-reviewed publications that
      provided information on the assessment tool used to evaluate the behavioural
      expression of pain in cats, in conscious animals (not anaesthetised cats), were
      included. RESULTS: No previous systematic reviews were identified. One hundred
      papers were included in the final assessment. Studies were primarily related to
      the assessment of pain in relation to surgical procedures, and no clear
      distinction was made concerning the onset of acute and chronic pain. Ten broad
      types of instrument to assess pain were identified, and generally the quality of
      evidence to support the use of the various instruments was poor. Only one
      specific instrument (UNESP-Botucatu scale) had published evidence of validity,
      reliability and sensitivity at the level of a randomised control trial, but with
      a positive rather than placebo control, and limited to its use in the
      ovariohysterectomy situation. The metrics used within the tools appeared to focus
      primarily on the sensory aspect of pain, with no study clearly discriminating
      between the sensory and affective components of pain. CONCLUSIONS AND RELEVANCE:
      Further studies are required to provide a higher quality of evidence for methods
      used to assess pain in cats. Furthermore, a consistent definition for acute and
      chronic pain is needed. Tools need to be validated that can detect pain in a
      range of conditions and by different evaluators (veterinary surgeons and owners),
      which consider both the sensory and emotional aspects of pain.

PMID- 25972248
TI  - Two Lovely Black Eyes; Oh, what a surprise!

PMID- 25972249
TI  - Biochemical Characterization and Computational Identification of Mycobacterium
      tuberculosis Pyrazinamidase in Some Pyrazinamide-Resistant Isolates of Iran.
AB  - Pyrazinamide (PZA) is one the first line anti-tuberculosis drugs that require
      activation by the pyrazinamidase (PZase). Most PZA-resistant Mycobacterium
      tuberculosis strains have mutations in the pncA gene which encoding PZase that
      result in the reduction or loss of the enzyme activity. Herein, we have examined
      how various mutations, which have been found from the PZA-resistant M.
      tuberculosis strains in Iran, modify the PZase activity. To elucidate the
      possible role of these mutations, namely A143T (MUT1), L151S (MUT2),
      A143T/T168A/E173K (MUT3), in the bioactivity of the enzyme, the PZase and mutant
      genes were cloned, functionally expressed and biochemically and computationally
      characterized. In comparison to the PZase enzyme, the enzymatic efficiency of
      mutant enzymes was decreased, with MUT2 indicating the largest enzymatic
      efficiency reduction. Homology models of mutants were constructed based on the
      PZase X-ray crystal structure. Molecular modeling and substrate docking revealed
      that the wild-type has much stronger binding affinity to PZA than the mutants
      whereas MUT2 has the weakest binding affinity. In addition, the molecular
      dynamics simulations and the essential dynamics results illustrated that the
      positions of the 51st to 71st residues were more dynamics in MUT2 as compared to
      the other atoms in PZase, MUT1 and MUT3 which could decrease the K(m) and k(cat)
      values of the enzymes.

PMID- 25972250
TI  - Diagnostic Radiology Resident and Fellow Workloads: A 12-Year Longitudinal Trend
      Analysis Using National Medicare Aggregate Claims Data.
AB  - PURPOSE: The aim of this study was to evaluate changes in diagnostic radiology
      resident and fellow workloads in recent years. METHODS: Berenson-Eggers Type of
      Service categorization was applied to Medicare Part B Physician/Supplier
      Procedure Summary Master Files to identify total and resident-specific claims for
      radiologist imaging services between 1998 and 2010. Data were extracted and
      subgroup analytics performed by modality. Volumes were annually normalized for
      active diagnostic radiology trainees. RESULTS: From 1998 to 2010, Medicare claims
      for imaging services rendered by radiologists increased from 78,901,255 to
      105,252,599 (+33.4%). Service volumes increased across all modalities: for
      radiography from 55,661,683 to 59,654,659 (+7.2%), for mammography from 5,780,624
      to 6,570,673 (+13.7%), for ultrasound from 5,851,864 to 9,853,459 (+68.4%), for
      CT from 9,351,780 to 22,527,488 (+140.9%), and for MR from 2,255,304 to 6,646,320
      (+194.7%). Total trainee services nationally increased 3 times as rapidly. On an
      average per trainee basis, however, the average number of diagnostic services
      rendered annually to Medicare Part B beneficiaries increased from 499 to 629
      (+26.1%). By modality, this represents an average change from 333 to 306
      examinations (-8.1%) for radiography, from 20 to 18 (-7.4%) for mammography, from
      37 to 56 (+49.7%) for ultrasound, from 88 to 202 (+129.1%) for CT, and from 20 to
      47 (+132.0%) for MRI. CONCLUSIONS: Between 1998 and 2010, the number of imaging
      examinations interpreted by diagnostic radiology residents and fellows on
      Medicare beneficiaries increased on average by 26% per trainee, with growth
      largely accounted for by disproportionate increases in more complex services (CT
      and MRI).

PMID- 25972251
TI  - Molecular epidemiology of community-onset methicillin-resistant Staphylococcus
      aureus infections in Israel.
AB  - Data on community-associated (CA) methicillin-resistant Staphylococcus aureus
      (MRSA) in Israel are scarce. The objective of this study was to characterize the
      major CA-MRSA clones in Israel. All clinical MRSA isolates detected in the
      community during a period of 2.5 years (2011-2013) from individuals insured by a
      major health maintenance organization in Israel were collected, with additional
      data from medical records. Antibiotic susceptibility patterns and staphylococcal
      chromosomal cassette mec (SCCmec) typing were determined. SCCmec IV and V
      isolates were further typed by pulsed-field gel electrophoresis (PFGE), spa
      typing, and detection of a panel of toxin genes. MRSA were detected in 280
      patients, mostly from skin infections. Patients with SCCmec IV (n = 120, 43 %)
      were younger (p < 0.0001) and reported less contact with healthcare facilities.
      Almost all isolates were trimethoprim-sulfamethoxazole susceptible (98 %). spa
      CC032, a typical nosocomial MRSA clone, accounted for 28 % of SCCmec IV. The two
      major CA-MRSA clones were t008 USA300 (13 %) and t991 (10 %); t991 was isolated
      mainly from children (75 %), was Panton-Valentine leukocidin (PVL) negative but
      eta-positive, and was typically susceptible to most antibiotic groups. PVL
      positive strains (n = 31) included mainly USA300 (52 %) and t019 (13 %). While
      multiple genetic lineages were evident among community-onset MRSA in Israel,
      approximately 20 % are typical CA-MRSA clones, mainly USA300 and a local clone,
      t991. 

PMID- 25972252
TI  - Erratum to: Tropicihabitans flavus gen. nov., sp. nov., a new member of the
      family Cellulomonadaceae.

PMID- 25972253
TI  - Microbe-dependent lymphatic migration of neutrophils modulates lymphocyte
      proliferation in lymph nodes.
AB  - Neutrophil recruitment to the site of injury is an essential first step of an
      anti-bacterial response. However, little is known about the basis for and
      relevance of neutrophil migration from inflamed tissue into lymphoid organs. We
      established a photoconversion-based system to monitor the fate of neutrophils
      recruited to inflamed skin. While neutrophils are efficiently recruited to sites
      of both microbial and sterile lesions, subsequent re-localization to draining
      lymph nodes happens only when bacteria are present in the primary lesion. Skin
      egress of neutrophils occurs via lymphatic vessels and is dependent on CD11b and
      CXCR4 but not CCR7. Neutrophils are the predominant immune cell to migrate from
      inflamed skin into lymph nodes where they augment lymphocyte proliferation.
      Furthermore, inhibition of neutrophil migration from skin reduces T-cell
      proliferation in draining lymph nodes. Thus neutrophils mediate rapid cellular
      communication between the initial injury site and secondary lymphoid organs and
      modulate immune responsiveness. 

PMID- 25972255
TI  - Periocular Squamous Cell Carcinoma: TNM Staging and Recurrence.
AB  - PURPOSE: To analyze the TNM stage, management, and recurrence rates of patients
      with histologically confirmed squamous cell carcinoma (SCC) of the eyelid.
      DESIGN: Retrospective case series from 3 Australian centers. PARTICIPANTS: A
      total of 254 cases of eyelid SCC from 254 patients (median age, 73 years; range,
      28-102 years; 159 were male). METHODS: Tumors were staged according to The
      American Joint Committee on Cancer 7th edition TNM criteria for eyelid carcinoma.
      MAIN OUTCOME MEASURES: Outcomes and recurrence rates according to TNM stage at
      presentation. RESULTS: A total of 25 cases (9.8%) were recurrent tumors. TNM
      classifications were as follows: T1N0M0, 74 patients (29.1%); T2aN0M0, 92
      patients (36.2%); T2bN0M0, 50 patients (19.7%); T3aN0M0, 31 patients (12.2%);
      T3bN0M0, 5 patients (2.0%); T2bN0M1, 1 patient (0.4%); and T3bN1M1, 1 patient
      (0.4%). Perineural invasion (PNI) was present histologically in 8.3% of cases.
      Treatment modalities included Mohs microsurgery (31.1%), wide local excision
      (WLE) with paraffin section control (21.7%), WLE with frozen-section control
      (19.3%), and excision without margin control (24.4%). Three cases did not receive
      treatment. Median follow-up was 40 months (range, <1-132 months). Local
      recurrence occurred in 17 treated patients (6.8%). The recurrence rate was 5.3%
      (12/226 patients) for primary tumors and 20% (5/25 patients) for recurrent tumors
      (P = 0.019). Four patients (1.6%) died of their disease during follow-up. Higher
      T stage was significantly associated with both PNI (P = 0.035) and local
      recurrence (P < 0.001). We could not identify a T-stage threshold below which
      there was no risk of recurrence, as evidenced by 3 T1 primary tumors that
      recurred. CONCLUSIONS: Higher T stage was significantly associated with local
      recurrence, and recurrent tumors had a 4-fold increased risk of further
      recurrence compared with primary tumors. Therefore, it may be reasonable to
      consider sentinel lymph node biopsy or close nodal surveillance and follow-up for
      patients with recurrent or high T-stage tumors. Of note, we could not identify a
      T-stage threshold below which there was no risk of recurrences; therefore,
      clinicians should be aware of the potential for low T-stage tumors to recur.

PMID- 25972254
TI  - A Randomized Trial of a Schlemm's Canal Microstent with Phacoemulsification for
      Reducing Intraocular Pressure in Open-Angle Glaucoma.
AB  - PURPOSE: To assess the safety and effectiveness of the Hydrus Microstent
      (Ivantis, Inc, Irvine, CA) with concurrent cataract surgery (CS) for reducing
      intraocular pressure (IOP) in open-angle glaucoma (OAG). DESIGN: Prospective,
      multicenter, randomized, single-masked, controlled clinical trial. PARTICIPANTS:
      One hundred eyes from 100 patients 21 to 80 years of age with OAG and cataract
      with IOP of 24 mmHg or less with 4 or fewer hypotensive medications and a washed
      out diurnal IOP (DIOP) of 21 to 36 mmHg. METHODS: On the day of surgery, patients
      were randomized 1:1 to undergo CS with the microstent or CS alone. Postoperative
      follow-up was at 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months. Washout of
      hypotensive medications was repeated at 12 and 24 months. MAIN OUTCOME MEASURES:
      Response to treatment was defined as a 20% or more decrease in washed out DIOP at
      12 and 24 months of follow-up compared with baseline. Mean DIOP at 12 and 24
      months, the proportion of subjects requiring medications at follow-up, and the
      mean number of medications were analyzed. Safety measures included change in
      visual acuity, slit-lamp observations, and adverse events. RESULTS: The
      proportion of patients with a 20% reduction in washed out DIOP was significantly
      higher in the Hydrus plus CS group at 24 months compared with the CS group (80%
      vs. 46%; P = 0.0008). Washed out mean DIOP in the Hydrus plus CS group was
      significantly lower at 24 months compared with the CS group (16.9+/-3.3 mmHg vs.
      19.2+/-4.7 mmHg; P = 0.0093), and the proportion of patients using no hypotensive
      medications was significantly higher at 24 months in the Hydrus plus CS group
      (73% vs. 38%; P = 0.0008). There were no differences in follow-up visual acuity
      between groups. The only notable device-related adverse event was focal
      peripheral anterior synechiae (1-2 mm in length). Otherwise, adverse event
      frequency was similar in the 2 groups. CONCLUSIONS: Intraocular pressure was
      clinically and statistically significantly lower at 2 years in the Hydrus plus CS
      group compared with the CS alone group, with no differences in safety.

PMID- 25972256
TI  - Retinal Development in Infants and Young Children with Achromatopsia.

PMID- 25972258
TI  - Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular
      Degeneration with Foveal Sparing.
AB  - PURPOSE: To describe the directional kinetics of the spread of geographic atrophy
      (GA) spread in eyes with age-related macular degeneration and foveal sparing.
      DESIGN: Prospective, noninterventional natural history study: Fundus
      Autofluorescence Imaging in Age-Related Macular Degeneration (FAM;
      clinicaltrials.gov identifier, NCT00393692). SUBJECTS: Participants of the FAM
      study exhibiting foveal sparing of GA. METHODS: Eyes were examined longitudinally
      with fundus autofluorescence (FAF; excitation wavelength, 488 nm; emission
      wavelength, >500 nm) and near infrared (NIR) reflectance imaging (Spectralis
      HRA+OCT or HRA2; Heidelberg Engineering, Heidelberg, Germany). Areas of foveal
      sparing and GA were measured by 2 independent readers using a semiautomated
      software tool that allows for combined NIR reflectance and FAF image grading
      (RegionFinder; Heidelberg Engineering). A linear mixed effect model was used to
      model GA kinetics over time. MAIN OUTCOME MEASURE: Change of GA lesion size over
      time (central vs. peripheral progression). RESULTS: A total of 47 eyes of 36
      patients (mean age, 73.8+/-7.5 years) met the inclusion criteria. Mean follow-up
      time was 25.2+/-16.9 months (range, 5.9-74.6 months). Interreader agreement for
      measurements of GA and foveal-sparing size were 0.995 and 0.946, respectively.
      Mean area progression of GA toward the periphery was 2.27+/-0.22 mm(2)/year and
      0.25+/-0.03 mm(2)/year toward the center. Analysis of square root-transformed
      data revealed a 2.8-fold faster atrophy progression toward the periphery than
      toward the fovea. Faster atrophy progression toward the fovea correlated with
      faster progression toward the periphery in presence of marked interindividual
      differences. CONCLUSIONS: The results demonstrate a significantly faster
      centrifugal than centripetal GA spread in eyes with GA and foveal sparing.
      Although the underlying pathomechanisms for differential GA progression remain
      unknown, local factors may be operative that protect the foveal retina-retinal
      pigment epithelial complex. Quantification of directional spread characteristics
      and modeling may be useful in the design of interventional clinical trials aiming
      to prolong foveal survival in eyes with GA.

PMID- 25972257
TI  - The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts
      in the Age-Related Eye Disease Study: AREDS Report No. 37.
AB  - PURPOSE: To evaluate whether dietary intake of luteiin/zeaxanthin and B vitamins
      is associated with cataract prevalence and incidence. DESIGN: Clinic-based,
      baseline cross-sectional and prospective cohort study designs. PARTICIPANTS:
      Three thousand one hundred fifteen patients (6129 eyes) enrolled in the Age
      Related Eye Disease Study 55 to 80 years of age followed up for mean of 9.6
      years. METHODS: Participants completed baseline food frequency questionnaires.
      Baseline and annual lens photographs were graded centrally. Multivariate models
      controlling for previously identified risk factors for cataracts tested for the
      association of cataracts with reported dietary intake, using the lowest quintile
      as reference. MAIN OUTCOME MEASURES: Cataract surgery, cataract status (type and
      severity) at baseline, and development of cataracts. RESULTS: At baseline,
      increased dietary riboflavin and B12 were associated inversely with nuclear and
      cortical lens opacities. In comparisons of persons with and without cataract,
      persons with the highest riboflavin intake versus those with the lowest intake
      had the following associations: mild nuclear cataract: odds ratio (OR), 0.78; 95%
      confidence interval (CI), 0.63-0.97; moderate nuclear cataract: OR, 0.62; 95% CI,
      0.43-0.90; and mild cortical cataract: OR, 0.80; 95% CI, 0.65-0.99. For B12, the
      results were: mild nuclear cataract: OR, 0.78; 95% CI, 0.63-0.96; moderate
      nuclear cataract: OR, 0.62; 95% CI, 0.43-0.88; and mild cortical cataract: OR,
      0.77; 95% CI, 0.63-0.95. Highest dietary B6 intake was associated with a
      decreased risk of moderate nuclear lens opacity developing compared with the
      lowest quintile (OR, 0.67; 95% CI, 0.45-0.99). Highest dietary intake levels of
      niacin and B12 were associated with a decreased risk of development of mild
      nuclear or mild cortical cataracts in participants not taking Centrum (Pfizer,
      New York, NY) multivitamins. For participants taking multivitamins during the
      study, the highest intake of dietary folate was associated with an increased risk
      of mild posterior subcapsular lens opacity development. No statistically
      significant associations were found between lutein plus zeaxanthin intake and
      presence at baseline or development of nuclear or cortical lens opacity outcomes.
      CONCLUSIONS: These findings are consistent with earlier studies suggesting that
      dietary intake of B vitamins may affect the occurrence of age-related lens
      opacities. Further investigations are warranted.

PMID- 25972259
TI  - Optic Nerve Head Deformation in Glaucoma: A Prospective Analysis of Optic Nerve
      Head Surface and Lamina Cribrosa Surface Displacement.
AB  - PURPOSE: To evaluate long-term, longitudinal displacement of the optic nerve head
      (ONH) and anterior lamina cribrosa surfaces in glaucoma patients imaged with
      spectral-domain optical coherence tomography (SD OCT). DESIGN: Prospective study.
      PARTICIPANTS: A total of 173 eyes of 108 subjects (88 with glaucoma and 20 normal
      subjects) followed for a mean of 5.3 years. METHODS: The optic disc was imaged
      with SD OCT at approximately 4-month intervals, and the ONH surface depth
      (ONHSD), anterior lamina cribrosa surface depth (ALCSD), and prelaminar tissue
      thickness (PTT) were measured. The reproducibility coefficients of ONHSD, ALCSD,
      and PTT were calculated from 2 baseline measurements of the glaucoma group.
      Change in ONHSD/ALCSD/PTT was confirmed when the differences between the first
      baseline and the latest 2 consecutive follow-up visits were greater than the
      corresponding reproducibility coefficient. Factors associated with ONHSD and
      ALCSD changes were identified with linear mixed modeling. MAIN OUTCOME MEASURES:
      Proportion of eyes with ONHSD/ALCSD change. RESULTS: Within the glaucoma group,
      23.9% (33 eyes) had confirmed ONHSD change (15.2% with posterior and 8.7% with
      anterior displacement) and 24.6% (34 eyes) had confirmed ALCSD change (12.3% with
      posterior and 12.3% with anterior displacement). Some 9.4% (13 eyes) showed a
      decrease in PTT, and 2.2% (3 eyes) showed an increase in PTT. The specificity for
      detection of ONHSD/ALCSD/PTT change was 91.4% (95% confidence interval [CI], 77.6
      97.0), 82.9% (95% CI, 67.3-91.9), and 94.3% (95% CI, 81.4-98.4), respectively.
      There were no significant differences in the proportion of eyes with visual field
      progression or history of filtration surgery between the groups with anterior and
      posterior displacement of ONH/anterior laminar surfaces (P >= 0.678). For each
      millimeter of mercury increase in the average intraocular pressure (IOP) during
      follow-up, the ONH and anterior laminar surfaces displaced posteriorly by 1.6 MUm
      and 2.0 MUm, respectively. An older age was associated with a decrease in
      magnitude of posterior displacement of the ONH and anterior laminar surfaces (P
      <= 0.009). CONCLUSIONS: The ONH and anterior laminar surfaces displaced not only
      posteriorly but also anteriorly (with reference to Bruch's membrane opening) in a
      significant portion of glaucoma patients. The magnitude of change was related to
      age and the averaged IOP during follow-up.

PMID- 25972260
TI  - Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in
      Patients with Retinal Vein Occlusion: The RELATE Trial.
AB  - PURPOSE: To determine whether scatter and grid laser photocoagulation (laser)
      adds benefit to ranibizumab injections in patients with macular edema from
      retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg ranibizumab.
      DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS:
      Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO).
      METHODS: Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks
      for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or
      ranibizumab alone. MAIN OUTCOME MEASURES: Mean change from baseline best
      corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for
      second randomization. RESULTS: Mean improvement from baseline BCVA at week 24 was
      15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6
      letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was
      significantly greater reduction from baseline mean central subfield thickness
      (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 MUm; P = 0.03). For the
      second randomization in CRVO patients, there was no significant difference from
      week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at
      week 48 (-3.3 vs. 0.0 letters), week 96 (+0.69 vs. -1.6 letters), or week 144
      (+0.4 vs. -6.7 letters), and a significant increase from week 24 mean CST at week
      48 (+94.7 vs. +15.2 MUm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a
      significant reduction from week 24 mean BCVA in ranibizumab plus laser versus
      ranibizumab at week 48 (-7.5 vs. +2.8; P < 0.01) and week 96 (-2.0 vs. +4.8; P <
      0.03), but not week 144, and there were no differences in mean CST change from
      week 24 at weeks 48, 96, or 144. Laser failed to increase edema resolution or to
      reduce the ranibizumab injections between weeks 24 and 144. CONCLUSIONS: In
      patients with macular edema resulting from RVO, there was no short-term
      clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg
      ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or
      number of ranibizumab injections obtained by addition of laser treatment to
      ranibizumab.

PMID- 25972261
TI  - Molecular cloning and potential function prediction of homologous SOC1 genes in
      tree peony.
AB  - KEY MESSAGE: The central flower integrator PsSOC1 was isolated and its expression
      profiles were analyzed; then the potential function of PsSOC1 in tree peony was
      postulated. The six flowering genes PrSOC1, PdSOC1, PsSOC1, PsSOC1-1, PsSOC1-2,
      and PsSOC1-3 were isolated from Paeonia rockii, Paeonia delavayi, and Paeonia
      suffruticosa, respectively. Sequence comparison analysis showed that the six
      genes were highly conserved and shared 99.41% nucleotide identity. Further
      investigation suggested PsSOC1 was highly homologous to the floral integrators,
      SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), from Arabidopsis. Phylogenetic
      analysis showed that the SOC1 protein clustering has family specificity and
      PsSOC1 has a close relationship with homologous SOC1 from Asteraceae species. The
      studies of PsSOC1's expression patterns in different buds and flower buds, and
      vegetative organs indicated that PsSOC1 could express in both vegetative and
      reproductive organs. While the expression of PsSOC1 in different developmental
      stages of buds was different; high expression levels of PsSOC1 occurred in the
      bud at the bud sprouting stage and the type I aborted the flower bud. PsSOC1
      expression was also shown to be affected by gibberellins (GA), low temperature,
      and photoperiod. One of the pathways that regulates tree peony flowering may be
      the GA-inductive pathway. Ectopic expression of PsSOC1 in tobacco demonstrated
      that greater PsSOC1 expression in the transgenic tobacco plants not only promoted
      plant growth, but also advanced the flowering time. Finally, the potential
      function of PsSOC1 in tree peony was postulated.

PMID- 25972262
TI  - Changes in fatty acid content and composition between wild type and CsHMA3
      overexpressing Camelina sativa under heavy-metal stress.
AB  - KEY MESSAGE: Under heavy-metal stress, CsHMA3 overexpressing transgenic Camelina
      plants displayed not only a better quality, but also a higher quantity of
      unsaturated fatty acids in their seeds compared with wild type. Camelina sativa
      L. belongs to the Brassicaceae family and is frequently used as a natural
      vegetable oil source, as its seeds contain a high content of fatty acids. In this
      study, we observed that, when subjected to heavy metals (Cd, Co, Zn and Pb), the
      seeds of CsHMA3 (Heavy-Metal P1B-ATPase 3) transgenic lines retained their
      original golden yellow color and smooth outline, unlike wild-type seeds.
      Furthermore, we investigated the fatty acids content and composition of wild type
      and CsHMA3 transgenic lines after heavy metal treatments compared to the control.
      The results showed higher total fatty acid amounts in seeds of CsHMA3 transgenic
      lines compared with those in wild-type seeds under heavy-metal stresses. In
      addition, the compositions of unsaturated fatty acids-especially 18:1 (oleic
      acid), 18:2 (linoleic acid; only in case of Co treatment), 18:3 (linolenic acid)
      and 20:1 (eicosenoic acid)-in CsHMA3 overexpressing transgenic lines treated with
      heavy metals were higher than those of wild-type seeds under the same conditions.
      Furthermore, reactive oxygen species (ROS) contents in wild-type leaves and roots
      when treated with heavy metal were higher than in CsHMA3 overexpressing
      transgenic lines. These results indicate that overexpression of CsHMA3 affects
      fatty acid composition and content-factors that are responsible for the fuel
      properties of biodiesel-and can alleviate ROS accumulation caused by heavy-metal
      stresses in Camelina. Due to these factors, we propose that CsHMA3 transgenic
      Camelina can be used for phytoremediation of metal-contaminated soil as well as
      for oil production.

PMID- 25972263
TI  - Characterization and classification of one new cytoplasmic male sterility (CMS)
      line based on morphological, cytological and molecular markers in non-heading
      Chinese cabbage (Brassica rapa L.).
AB  - KEY MESSAGE: A new non-heading Chinese cabbage CMS line M119A was characterized
      and specific molecular markers were developed to classify different CMS types.
      One new non-heading Chinese cabbage (Brassica rapa L.) cytoplasmic male sterile
      (CMS) line M119A was obtained by interspecific crosses between the recently
      discovered hau CMS line of Brassica juncea and B. rapa. Furthermore, the line was
      characterized and compared with other five isonuclear-alloplasmic CMS lines. The
      M119A line produced six stamens without pollen and only two stamen fused together
      in fewer flowers. Tissue section indicated that anther abortion in M119A may have
      occurred during differentiation of the archesporial cells without pollen sac. All
      the six CMS lines were grouped into three types based on the presence of three
      PCR fragments of 825, 465 and 772 bp amplified with different mitochondrial genes
      specific primers. The 825-bp fragment was amplified both in 09-10A and H201A
      using the specific primer pair P-orf224-atp6, and showed 100 % identity with the
      mitochondrial gene of pol CMS. The 465-bp fragment was amplified in 30A and 105A
      using the primer pair P-orf138 and shared 100 % identity with the mitochondrial
      gene of ogu CMS. The 772-bp fragment was amplified in M119A and H203A using the
      primer pair P-orf288 and showed 100 % identity with the mitochondrial gene of hau
      CMS. Therefore, these markers could efficiently distinguish different types of
      isonuclear-alloplasmic CMS lines of non-heading Chinese cabbage, which were
      useful for improving the efficiency of cross-breeding and heterosis utilization
      in cruciferous vegetables.

PMID- 25972264
TI  - Late urinary toxicity modeling after stereotactic body radiotherapy (SBRT) in the
      definitive treatment of localized prostate cancer.
AB  - BACKGROUND: Late urinary symptom flare has been shown to occur in a small subset
      of men treated with ultra- hypofractionated stereotactic body radiotherapy (SBRT)
      for prostate cancer. The purpose of this study was to use normal tissue
      complication probability modeling in an effort to derive SBRT specific dosimetric
      predictor's of late urinary flare. MATERIAL AND METHODS: Two hundred and sixteen
      men were treated for localized prostate cancer using ultra- hypofractionated
      SBRT. A dose of 35-36.25 Gy in 5 fractions was delivered to the prostate and
      proximal seminal vesicles. Functional surveys were conducted before and after
      treatment to assess late toxicity. Phenomenologic NTCP models were fit to bladder
      DVHs and late urinary flare outcomes using maximum likelihood estimation.
      RESULTS: Twenty-nine patients experienced late urinary flare within two years of
      completion of treatment. Fitting of bladder DVH data to a Lyman NTCP model
      resulted in parameter estimates of m, TD50, and n of 0.19 (0-0.47), 38.7 Gy (31.1
      46.4), and 0.13 (-0.14-0.41), respectively. Subsequent fit to a hottest volume
      probit model revealed a significant association of late urinary flare with dose
      to the hottest 12.7% of bladder volume. Multivariate analysis resulted in a final
      model that included patient age and hottest volume probit model predictions.
      Kaplan-Meier analysis demonstrated a two-year urinary flare free survival of
      95.7% in patients 65 years or older with a bladder D12.7% of 33.5 Gy or less,
      compared to 74.5% in patients meeting none of these criteria. CONCLUSION: NTCP
      modeling of late urinary flare after ultra-hypofractionated prostate SBRT
      demonstrates a relatively small volume effect for dose to the bladder, suggesting
      that reduction of volume receiving elevated dose will result in decreased
      incidence of late urinary toxicity. Future studies will be needed to examine the
      impact of dose to other potential sources of late genitourinary toxicity.

PMID- 25972265
TI  - Positive correlation between occlusion rate and nidus size of proton beam treated
      brain arteriovenous malformations (AVMs).
AB  - BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the
      brain has been performed in Uppsala since 1991. An earlier study based on the
      first 26 patients concluded that proton beam can be used for treating large and
      medium sized AVMs that were considered difficult to treat with photons due to the
      risk of side effects. In the present study we analyzed the result from treating
      the subsequent 65 patients. MATERIAL AND METHODS: A retrospective review of the
      patients' medical records, treatment protocols and radiological results was done.
      Information about gender, age, presenting symptoms, clinical course, the size of
      AVM nidus and rate of occlusion was collected. Outcome parameters were the
      occlusion of the AVM, clinical outcome and side effects. RESULTS: The rate of
      total occlusion was overall 68%. For target volume 0-2 cm(3) it was 77%, for 3-10
      cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress
      of the AVM had significantly smaller target volumes (p < 0.009) higher fraction
      dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The
      target volume was an independent predictor of total occlusion (p = 0.03). There
      was no difference between those with and without total occlusion regarding mean
      age, gender distribution or symptoms at diagnosis. Forty-one patients developed a
      mild radiation-induced brain edema and this was more common in those that had
      total occlusion of the AVM. Two patients had brain hemorrhages after treatment.
      One of these had no effect and the other only partial occlusion from proton
      beams. Two thirds of those presenting with seizures reported an improved seizure
      situation after treatment. CONCLUSION: Our observations agree with earlier
      results and show that proton beam irradiation is a treatment alternative for
      brain AVMs since it has a high occlusion rate even in larger AVMs.

PMID- 25972266
TI  - Tackling the emperor's wisdom: heat shock proteins to halt and reverse atrial
      fibrillation at its roots.

PMID- 25972267
TI  - Dose-dependent micronuclei formation in normal human fibroblasts exposed to
      proton radiation.
AB  - Micronuclei are small extranuclear bodies resulting from chromosome fragments or
      the whole chromosomes secluded from daughter nuclei during mitosis. The number of
      radiation-induced micronuclei reflects the level of chromosomal damage and
      relates to an absorbed dose and quality of incident ionizing radiation. The aim
      of the present study was to determine the micronucleus formation as a specific
      biological marker for acute radiation-induced DNA damage in normal human
      fibroblasts exposed to 30-MeV protons and Co-60 gamma radiation. We found a
      linear increase in binuclear cells containing micronuclei for absorbed doses from
      1 to 5 Gy for both radiation modalities. However, the total number of micronuclei
      in binuclear cells follows a linear-quadratic dose dependence. In case of human
      exposure to mixed radiation fields or high LET radiation, the proportion of
      binuclear cells containing micronuclei from all binuclear cells can thus serve as
      a good biomarker of radiation-induced DNA damage. 

PMID- 25972268
TI  - Toward the development of transcriptional biodosimetry for the identification of
      irradiated individuals and assessment of absorbed radiation dose.
AB  - The most frequently used and the best established method of biological dosimetry
      at present is the dicentric chromosome assay, which is poorly suitable for a mass
      casualties scenario. This gives rise to the need for the development of new, high
      throughput assays for rapid identification of the subjects exposed to ionizing
      radiation. In the present study, we tested the usefulness of gene expression
      analysis in blood cells for biological dosimetry. Human peripheral blood from
      three healthy donors was X-irradiated with doses of 0 (control), 0.6, and 2 Gy.
      The mRNA level of 16 genes (ATF3, BAX, BBC3, BCL2, CDKN1A, DDB2, FDXR, GADD45A,
      GDF15, MDM2, PLK3, SERPINE1, SESN2, TNFRSF10B, TNFSF4, and VWCE) was assessed by
      reverse transcription quantitative PCR 6, 12, 24, and 48 h after exposure with
      ITFG1 and DPM1 used as a reference genes. The panel of radiation-responsive genes
      was selected comprising GADD45A, CDKN1A, BAX, BBC3, DDB2, TNFSF4, GDF15, and
      FDXR. Cluster analysis showed that DeltaC t values of the selected genes
      contained sufficient information to allow discrimination between irradiated and
      non-irradiated blood samples. The samples were clearly grouped according to the
      absorbed doses of radiation and not to the time interval after irradiation or to
      the blood donor. 

PMID- 25972269
TI  - Association between diastolic dysfunction and future atrial fibrillation in the
      Tromso Study from 1994 to 2010.
AB  - OBJECTIVE: To investigate the association between echocardiographic measurements
      with emphasis on diastolic dysfunction and risk of atrial fibrillation (AF) in a
      population-based cohort study. METHODS: We followed 2406 participants from the
      Tromso Study from 1994 to 2010. Left atrial (LA) size and mitral Doppler indices
      as measured by echocardiography were used for evaluating diastolic dysfunction.
      Information concerning age, systolic blood pressure, height, heart rate, body
      mass index, total and high-density lipoprotein cholesterol, self-reported use of
      alcohol, smoking, coffee, physical activity, antihypertensive treatment,
      prevalent coronary heart disease, valvular heart disease, heart failure,
      hypertrophy, diabetes and palpitations were obtained at baseline. The outcome
      measure was clinical AF, documented by an ECG. RESULTS: AF was detected in 462
      subjects (193 women). Mean age at baseline was 62.6 years. Incidence rate of
      clinical AF was 12.6 per 1000 person-years. In multivariable Cox proportional
      hazards regression analysis, moderately enlarged LA was associated with 60% (95%
      CI 1.2 to 2.0) increased risk of AF. Severely enlarged LA had HR for AF of 4.2
      (95% CI 2.7 to 6.5) with p value for linear trend <0.001, and the association was
      similar in both sexes. Abnormal mitral Doppler flow adjusted for predictor
      variables did not show a statistically significant association with AF risk.
      However, when LA size was also adjusted for, the risk of AF increased by 30% (95%
      CI 1.0 to 1.6). CONCLUSIONS: Our findings suggest that enlarged LA as a measure
      for diastolic dysfunction is a significant risk factor for AF in both sexes, and
      adding measures of abnormal diastolic flow increased the predictive ability
      significantly.

PMID- 25972270
TI  - Complete revascularisation in patients with diabetes.

PMID- 25972272
TI  - Incarceration of one or two phosphate or arsenate species within nanojars, capped
      nanojars and nanohelicages: helical chirality from two closely-spaced, head-to
      head PO4(3-) or AsO4(3-) ions.
AB  - Unprecedentedly strong binding of HXO4(2-) and XO4(3-) ions (X = P or As) within
      self-assembled nanohosts with protein-like anion binding cavities is reported.
      One of the nanohosts binds two XO4(3-) ions at an unusually short distance,
      resulting in helical chirality. 

PMID- 25972271
TI  - Quality of life and its association with direct medical costs for COPD in urban
      China.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the leading
      causes of death worldwide. Few studies have focused on the quality of life (QoL)
      associated medical costs for COPD in China. METHODS: A cross-sectional survey of
      678 COPD patients was conducted in four major cities (Beijing, Shanghai,
      Guangzhou and Chengdu), China, in 2011. Data on socio-demographic information,
      health conditions and medical costs were collected through a face-to-face
      interview combined with medical record searching. The EuroQol (EQ-5D) health
      questionnaire was applied to assess the QoL of COPD patients. RESULTS: Among 678
      patients with COPD, nearly 40% had difficulties in mobility, usual activities and
      pain/discomfort, one third had various degrees of anxiety/depression, and one
      fifth had difficulties in self-care. The COPD patients had a median utility score
      of 0.768 and a median visual analog scale score of 70. The degree of difficulties
      in any dimensions significantly increased, and utility and health scores
      decreased with severity of the disease. Age, gender and disease severity were
      significantly associated with the quality of life after taking other covariates
      into consideration. Poorer QoL was a significant indicator of higher direct
      medical costs for COPD patients. CONCLUSION: Impaired quality of life was
      significantly linked to increased medical costs for COPD patients and could be an
      important measure for policy- and decision-making in COPD care.

PMID- 25972273
TI  - Antipsychotic drug use in pregnancy: high dimensional, propensity matched,
      population based cohort study.
AB  - OBJECTIVE: To evaluate maternal medical and perinatal outcomes associated with
      antipsychotic drug use in pregnancy. DESIGN: High dimensional propensity score
      (HDPS) matched cohort study. SETTING: Multiple linked population health
      administrative databases in the entire province of Ontario, Canada. PARTICIPANTS:
      Among women who delivered a singleton infant between 2003 and 2012, and who were
      eligible for provincially funded drug coverage, those with >= 2 consecutive
      prescriptions for an antipsychotic medication during pregnancy, at least one of
      which was filled in the first or second trimester, were selected. Of these
      antipsychotic drug users, 1021 were matched 1:1 with 1021 non-users by means of a
      HDPS algorithm. MAIN OUTCOME MEASURES: The main maternal medical outcomes were
      gestational diabetes, hypertensive disorders of pregnancy, and venous
      thromboembolism. The main perinatal outcomes were preterm birth (<37 weeks), and
      a birth weight <3rd or >97th centile. Conditional Poisson regression analysis was
      used to generate rate ratios and 95% confidence intervals, adjusting for
      additionally prescribed non-antipsychotic psychotropic medications. RESULTS:
      Compared with non-users, women prescribed an antipsychotic medication in
      pregnancy did not seem to be at higher risk of gestational diabetes (rate ratio
      1.10 (95% CI 0.77 to 1.57)), hypertensive disorders of pregnancy (1.12 (0.70 to
      1.78)), or venous thromboembolism (0.95 (0.40 to 2.27)). The preterm birth rate,
      though high among antipsychotic users (14.5%) and matched non-users (14.3%), was
      not relatively different (rate ratio 0.99 (0.78 to 1.26)). Neither birth weight
      <3rd centile or >97th centile was associated with antipsychotic drug use in
      pregnancy (rate ratios 1.21 (0.81 to 1.82) and 1.26 (0.69 to 2.29) respectively).
      CONCLUSIONS: Antipsychotic drug use in pregnancy had minimal evident impact on
      important maternal medical and short term perinatal outcomes. However, the rate
      of adverse outcomes is high enough to warrant careful assessment of maternal and
      fetal wellbeing among women prescribed an antipsychotic drug in pregnancy.

PMID- 25972274
TI  - Photochemical properties in flag leaves of a super-high-yielding hybrid rice and
      a traditional hybrid rice (Oryza sativa L.) probed by chlorophyll a fluorescence
      transient.
AB  - Chlorophyll a fluorescence of flag leaves in a super-high-yielding hybrid rice
      (Oryza sativa L.) LYPJ, and a traditional hybrid rice SY63 cultivar with lower
      grain yield, which were grown in the field, were investigated from emergence
      through senescence of flag leaves. As the flag leaf matured, there was an
      increasing trend in photosynthetic parameters such as quantum efficiency of
      primary photochemistry ([Formula: see text] Po) and efficiency of electron
      transport from PS II to PS I (Psi Eo). The overall photosynthetic performance
      index (PIABS) was significantly higher in the high-yielding LYPJ compared to SY63
      during the entire reproductive stage of the plant, the same to MDA content.
      However, [Formula: see text] Po(=F V/F M), an indicator of the primary
      photochemistry of the flag leaf, did not display significant changes with leaf
      age and was not significantly different between the two cultivars, suggesting
      that PIABS is a more sensitive parameter than [Formula: see text] Po (=F V/F M)
      during leaf age for distinguishing between cultivars differing in yield. 

PMID- 25972275
TI  - [Pain therapy in German long-term care facilities in a European comparison.
      Results of the SHELTER study].
AB  - BACKGROUND: A considerable number of nursing home residents suffering from pain
      are insufficiently treated. International comparisons of pain management in
      German (GER) and other European (EU) nursing homes are still lacking. OBJECTIVE:
      This study compared the treatment of pain in GER and EU nursing homes in order to
      improve allocation of therapeutic resources. MATERIAL AND METHODS: A cross
      sectional study was carried out with 4156 residents assessed using the interRAI
      instrument for long-term care facilities, including pharmacological and non
      pharmacological pain management modalities. Only those residents reporting pain
      were included in the analyses (n = 1900 from EU and 245 from GER). Descriptive
      analyses and analyses of correlations between different parameters and pain were
      performed. RESULTS: More than three quarters of the residents with at least
      moderate pain received pharmacological treatment (GER: 77.4 % and EU: 79.3 %).
      Combination therapy (pharmacological and non-pharmacological) was more frequent
      in Germany (approximately  13 %). Even in cases of moderate to severe pain one
      third of GER compared to one quarter of the EU residents received either no
      analgesic treatment or only on a when needed basis (PRN). Differences were also
      seen in drugs used (GER metamizole). The amount of PRN was higher in Germany
      (approximately 13 %, alone or in combination). Only 5 % received the recommended
      level of non-pharmacological treatment. Pain severity and decubitus were
      identified as important triggers for pharmacological treatment. Non
      pharmacological treatment was used less often than analgesics (EU: 39.2 %, GER:
      46.8 %). There were no differences regarding administration frequency and
      intensity of non-pharmacological treatments in residents with or without pain;
      however, non-pharmacological treatment was used less often in residents with
      successful pharmacological treatment. CONCLUSION: The data demonstrate
      significant deficits in the recognition and treatment of pain in residents living
      in German or other European nursing home facilities. Further scope for
      improvement is seen in better recognition of relevant pain, in the adequate use
      of PRN and long-term medication and especially in the use of activating non
      pharmacological treatment.

PMID- 25972276
TI  - Early axonal Guillain-Barre syndrome with normal peripheral conduction: imaging
      evidence for changes in proximal nerve segments.

PMID- 25972277
TI  - The role of clock genes and circadian rhythm in the development of cardiovascular
      diseases.
AB  - The time of onset of cardiovascular disorders such as myocardial infarctions or
      ventricular arrhythmias exhibits a circadian rhythm. Diurnal variations in
      autonomic nervous activity, plasma cortisol level or renin-angiotensin activity
      underlie the pathogenesis of cardiovascular diseases. Transcriptional
      translational feedback loop of the clock genes constitute a molecular clock
      system. In addition to the central clock in the suprachiasmatic nucleus, clock
      genes are also expressed in a circadian fashion in each organ to make up the
      peripheral clock. The peripheral clock seems to be beneficial for anticipating
      external stimuli and thus contributes to the maintenance of organ homeostasis.
      Loss of synchronization between the central and peripheral clocks also augments
      disease progression. Moreover, accumulating evidence shows that clock genes
      affect inflammatory and intracellular metabolic signaling. Elucidating the roles
      of the molecular clock in cardiovascular pathology through the identification of
      clock controlled genes will help to establish a novel therapeutic approach for
      cardiovascular disorders. 

PMID- 25972279
TI  - Effectiveness of a blended web-based intervention on return to work for sick
      listed employees with common mental disorders: results of a cluster randomized
      controlled trial.
AB  - BACKGROUND: Common mental disorders are strongly associated with long-term
      sickness absence, which has negative consequences for the individual employee's
      quality of life and leads to substantial costs for society. It is important to
      focus on return to work (RTW) during treatment of sick-listed employees with
      common mental disorders. Factors such as self-efficacy and the intention to
      resume work despite having symptoms are important in the RTW process. We
      developed "E-health module embedded in Collaborative Occupational health care"
      (ECO) as a blended Web-based intervention with 2 parts: an eHealth module
      (Return@Work) for the employee aimed at changing cognitions of the employee
      regarding RTW and a decision aid via email supporting the occupational physician
      with advice regarding treatment and referral options based on monitoring the
      employee's progress during treatment. OBJECTIVE: This study evaluated the effect
      of a blended eHealth intervention (ECO) versus care as usual on time to RTW of
      sick-listed employees with common mental disorders. METHODS: The study was a 2
      armed cluster randomized controlled trial. Employees sick-listed between 4 and 26
      weeks with common mental disorder symptoms were recruited by their occupational
      health service or employer. The employees were followed up to 12 months. The
      primary outcome measures were time to first RTW (partial or full) and time to
      full RTW. Secondary outcomes were response and remission of the common mental
      disorder symptoms (self-assessed). RESULTS: A total of 220 employees were
      included: 131 participants were randomized to the ECO intervention and 89 to care
      as usual (CAU). The duration until first RTW differed significantly between the
      groups. The median duration was 77.0 (IQR 29.0-152.3) days in the CAU group and
      50.0 (IQR 20.8-99.0) days in the ECO group (hazard ratio [HR] 1.390, 95% CI 1.034
      1.870, P=.03). No significant difference was found for duration until full RTW.
      Treatment response of common mental disorder symptoms did not differ
      significantly between the groups, but at 9 months after baseline significantly
      more participants in the ECO group achieved remission than in the CAU group (OR
      2.228, 95% CI 1.115-4.453, P=.02). CONCLUSIONS: The results of this study showed
      that in a group of sick-listed employees with common mental disorders, applying
      the blended eHealth ECO intervention led to faster first RTW and more remission
      of common mental disorder symptoms than CAU. TRIAL REGISTRATION: Netherlands
      Trial Register NTR2108;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2108. (Archived by
      WebCite at http://www.webcitation.org/6YBSnNx3P).

PMID- 25972281
TI  - Misled by the Morning "Fasting" Plasma Glucose.
AB  - Because of its ease and simplicity of its measurement, the morning fasting plasma
      glucose (FPG), has been as used a surrogate marker for the entire basal day when
      titrating once-nightly basal insulin. Common in obese insulin-treated patients
      with type 2 diabetes, late and large evening meals elevate the FPG. This has led
      to dosing of basal insulin well beyond the basal requirements and contributes to
      hypoglycemia and weight gain seen with this therapy. It is recommended that
      during basal insulin titration, the evening meal be limited and hypoglycemia be
      monitored early in the morning, that bewitching time when the "peakless" basal
      insulin's action is peaking and the predawn phenomenon insulin sensitivity is
      higher. 

PMID- 25972280
TI  - Use of an Intravascular Fluorescent Continuous Glucose Sensor in ICU Patients.
AB  - BACKGROUND: Hyperglycemia and hypoglycemia are associated with adverse clinical
      outcomes in intensive care patients. In product development studies at 4 ICUs,
      the safety and performance of an intravascular continuous glucose monitoring (IV
      CGM) system was evaluated in 70 postsurgical patients. METHODS: The GluCath
      System (GluMetrics, Inc) used a quenched chemical fluorescence mechanism to
      optically measure blood glucose when deployed via a radial artery catheter or
      directly into a peripheral vein. Periodic ultrasound assessed blood flow and
      thrombus formation. Patient glucose levels were managed according to the standard
      of care and existing protocols at each site. Reference blood samples were
      acquired hourly and compared against prospectively calibrated sensor results.
      RESULTS: In all, 63 arterial sensors and 9 venous sensors were deployed in 70
      patients. Arterial sensors did not interfere with invasive blood pressure
      monitoring, sampling or other aspects of patient care. A majority of venous
      sensors (66%) exhibited thrombus on ultrasound. In all, 89.4% (1383/1547) of
      arterial and 72.2% (182/252) of venous measurements met ISO15197:2003 criteria
      (within 20%), and 72.7% (1124/1547) of arterial and 56.3% (142/252) of venous
      measurements met CLSI POCT 12-A3 criteria (within 12.5%). The aggregate mean
      absolute relative difference (MARD) between the sensors and the reference was
      9.6% for arterial and 14.2% for venous sensors. CONCLUSIONS: The GluCath System
      exhibited acceptable accuracy when deployed in a radial artery for up to 48 hours
      in ICU patients after elective cardiac surgery. Accuracy of venous deployment was
      substantially lower with significant rates of intravascular thrombus observed
      using ultrasound.

PMID- 25972282
TI  - Model Predictive Control for Type 1 Diabetes Based on Personalized Linear Time
      Varying Subject Model Consisting of Both Insulin and Meal Inputs: An in Silico
      Evaluation.

PMID- 25972278
TI  - ROS signaling and redox biology in endothelial cells.
AB  - The purpose of this review is to provide an overview of redox mechanisms, sources
      and antioxidants that control signaling events in ECs. In particular, we describe
      which molecules are involved in redox signaling and how they influence the
      relationship between ECs and other vascular component with regard to
      angiogenesis. Recent and new tools to investigate physiological ROS signaling
      will be also discussed. Such findings are providing an overview of the ROS
      biology relevant for endothelial cells in the context of normal and pathological
      angiogenic conditions. 

PMID- 25972283
TI  - Surgical Revascularization in North American Adults with Moyamoya Phenomenon:
      Long-Term Angiographic Follow-up.
AB  - BACKGROUND: North American and Asian forms of moyamoya have distinct clinical
      characteristics. Asian adults with moyamoya are known to respond better to direct
      versus indirect revascularization. It is unclear whether North American adults
      with moyamoya have a similar long-term angiographic response to direct versus
      indirect bypass. METHODS: A retrospective review of surgical revascularization
      for adult moyamoya phenomenon was performed. Preoperative and postoperative
      cerebral angiograms underwent consensus review, with degree of revascularization
      quantified as extent of new middle cerebral artery (MCA) territory filling.
      RESULTS: Late angiographic follow-up was available in 15 symptomatic patients who
      underwent 20 surgical revascularization procedures. In 10 hemispheres treated
      solely with indirect arterial bypass, 3 had 2/3 revascularization, 4 had 1/3
      revascularization, and 3 had no revascularization of the MCA territory. In the 10
      hemispheres treated with direct arterial bypass (8 as a stand-alone procedure and
      2 in combination with an indirect procedure), 2 had complete revascularization, 7
      had 2/3 revascularization, and 1 had 1/3 revascularization. Direct bypass
      provided a higher rate of "good" angiographic outcome (complete or 2/3
      revascularization) when compared with indirect techniques (P = .0198).
      CONCLUSIONS: Direct bypass provides a statistically significant, more consistent,
      and complete cerebral revascularization than indirect techniques in this patient
      population. This is similar to that reported in the Asian literature, which
      suggests that the manner of presentation (ischemia in North American adults
      versus hemorrhage in Asian adults) is likely not a contributor to the extent of
      revascularization achieved after surgical intervention.

PMID- 25972284
TI  - The Impact of Oral Intake of Dydrogesterone on Fetal Heart Development During
      Early Pregnancy.
AB  - Congenital heart disease is the most frequent form of congenital anomaly in
      newborn infants and accounts for more than a quarter of all serious congenital
      afflictions worldwide. A genetic etiology is identified in <20 % of cases of
      congenital heart defects, and in most cases the etiology remains a mystery. In
      the context of the health burden caused by congenital heart disease, the
      contribution of non-inherited risk factors is important especially if it turns
      out to be caused by a drug which can be avoided during pregnancy. We sought to
      determine whether maternal dydrogesterone treatment in early pregnancy is
      associated with congenital heart disease in the infant. We conducted a
      retrospective case-control study of birth defects and associated risk factors.
      Data were obtained and compared between 202 children born with congenital heart
      disease and a control group consisting of 200 children. All children were born in
      the period of 2010-2013. Dydrogesterone exposure was defined as any reported use
      during the first trimester of pregnancy. Exclusion criteria included stillbirths,
      children with chromosomal abnormalities and infants of mothers with chronic
      medical illnesses, e.g., diabetes. Binary logistic regression analyses were used
      to analyze the data and attempt to identify a causal relationship between drug
      exposure and congenital heart disease. Mothers of children born with congenital
      heart disease received more dydrogesterone during first trimester of pregnancy
      than mothers of children in the control group [adjusted odds ratio 2.71; (95 % CI
      1.54-4.24); P = 0.001]. We identified a positive association between
      dydrogesterone usage during early pregnancy and congenital heart disease in the
      offspring. Nevertheless, further studies are needed to confirm these results.

PMID- 25972285
TI  - Left Ventricular Remodeling and Function in Children with Biventricular
      Circulation After Fetal Aortic Valvuloplasty.
AB  - Fetal aortic valvuloplasty (FAV) has shown promise in averting the progression of
      fetal aortic stenosis to hypoplastic left-heart syndrome. Altered loading
      conditions due to valvar disease, intrinsic endomyocardial abnormalities, and
      procedures that alter endomyocardial mechanics may place patients with
      biventricular circulation (BiV) after FAV at risk of abnormal LV remodeling and
      function. Using the most recent echo data on BiV patients after technically
      successful FAV (n = 34), we evaluated LV remodeling pattern, risk factors for
      pathologic LV remodeling, and the association between LV remodeling pattern and
      LV function. Median age at follow-up was 4.7 years (range 1.0-12.5). Cardiac
      interventions were common. At latest follow-up, no patient had hypoplastic LV.
      Nineteen patients (55 %) had dilated LV, and five (16 %) patients had severely
      dilated LV. LV remodeling patterns were as follows: 12 (35 %) normal ventricle,
      11 (32 %) mixed hypertrophy, 8 (24 %) eccentric hypertrophy or remodeling, and 3
      (9 %) concentric hypertrophy. Univariate factors associated with pathologic LV
      remodeling were long-standing AR, >=2 cardiac interventions, EFE resection, and
      aortic or mitral regurgitation >= moderate at most recent follow-up. In
      multivariate analysis, only long-standing AR fraction remained associated with
      pathologic remodeling. Pathologic LV remodeling was associated with depressed
      ejection fraction, lower septal E', and higher E/E'. Pathologic LV remodeling,
      primarily eccentric or mixed hypertrophy, is common in BiV patients after FAV and
      is related to LV loading conditions imposed by valvar disease. Pathologic
      remodeling is associated with both systolic and diastolic dysfunction in this
      population.

PMID- 25972286
TI  - Comparison of the safety, tolerability, and pharmacokinetics of fidaxomicin in
      healthy Japanese and caucasian subjects.
AB  - BACKGROUND AND OBJECTIVES: Fidaxomicin treatment of Clostridium difficile
      infection is known to produce minimal systemic exposure, as the antibacterial
      (antibiotic) remains primarily in the gut. In this randomized, double-blind,
      placebo-controlled study, the safety, tolerability, and pharmacokinetics of
      single and multiple ascending doses of fidaxomicin were evaluated in healthy
      Japanese and Caucasian subjects. METHODS: Thirty-six healthy subjects were
      randomly assigned in a 3:1 ratio to receive either fidaxomicin or placebo. Cohort
      1 (100 mg) and Cohort 2 (200 mg) comprised 12 Japanese subjects each and Cohort 3
      (200 mg) comprised 12 Caucasian subjects. Subjects received a single dose of the
      study drug on Day 1 and received multiple doses for 10 days after a wash-out
      period. RESULTS: After multiple 200 mg dosing of fidaxomicin, both mean maximum
      plasma concentrations (C max) in Japanese (8.7 +/- 5.3 ng/mL) and Caucasian (7.0
      +/- 3.7 ng/mL) subjects and the area under the concentration-time curve (AUC)
      were higher in Japanese subjects (58.5 +/- 36.7 ng.h/mL) than in Caucasian
      subjects (37.6 +/- 15.7 ng.h/mL), although variation in both groups was large.
      The mean fecal concentrations of fidaxomicin in Japanese and Caucasian subjects
      were 2669 and 2181 MUg/g, respectively. The possibly study drug-related adverse
      events were diarrhea (n = 1), feeling hot (n = 1), and hypersomnia (n = 2), which
      were mild in severity. CONCLUSIONS: In both Japanese and Caucasian subjects,
      fidaxomicin demonstrated similarly minimal systemic absorption, and was mainly
      excreted in feces. Fidaxomicin was safe and well-tolerated in all subjects.

PMID- 25972287
TI  - Autoimmune Lymphoproliferative Syndrome with Red Cell Aplasia.
AB  - Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of
      abnormal lymphocyte apoptosis, leading to chronic lymphoproliferation. It
      presents as lymphadenopathy, hepatosplenomegaly and autoimmune phenomena. Pure
      red cell aplasia is characterized by normochromic normocytic anemia,
      reticulocytopenia, and absence of erythroblasts from a normal bone marrow. Only
      few lymphoproliferative disorders have been associated with erythroid aplasia.
      The authors are reporting a case of ALPS associated with red cell aplasia in a 7
      y-old girl.

PMID- 25972288
TI  - Influence of Vitamin D Receptor Gene Fok1 Polymorphism on Bone Mass Accrual Post
      Calcium and Vitamin D Supplementation.
AB  - OBJECTIVE: To examine the association of vitamin D receptor (VDR) gene
      polymorphisms of the Fok1 locus on bone mass accrual in Indian girls used to a
      low calcium intake. METHODS: An intervention trial was undertaken in 102 girls
      aged 8-16 y, attending a state run school in Pune city, India. All girls received
      500 mg calcium daily and 30,000 IU of vitamin D3 quarterly for one year. Dietary
      calcium intake was evaluated. Bone mineral content (BMC), bone area (BA) and bone
      mineral density (BMD) were measured at total body using Dual Energy X-ray
      Absorptiometry (Lunar DPX-PRO). Polymorphisms of the Fok1 locus of the vitamin D
      Receptor (VDR) gene were detected using SYBR Green quantitative polymerase chain
      reaction. RESULTS: The prevalence of Fok1 polymorphism was 43.1% (Ff), 9.8% (ff)
      and 47.1% (FF). At baseline, FF genotype had significantly lower BMD as compared
      to ff and Ff genotype (p < 0.05). At baseline, majority of girls (82.4%) were
      hypocalcemic with low calcium intake. Post-supplementation, FF genotype had
      significantly lower bone mass as compared to ff and Ff genotype. Significant
      increase in BMC [Ff (17.9%); ff (18.1%); FF (17.4%)], and BMD [Ff (5.4 %); ff
      (6.3%); FF (4.8%)] was observed post supplementation (p value < 0.05), though
      percentage increase in BMC and BMD was similar for three Fok1 polymorphisms (p >
      0.1). CONCLUSIONS: VDR gene polymorphism, as defined by Fok1 genotype had no
      positive influence on bone mass accrual in response to calcium supplementation.

PMID- 25972289
TI  - Substance Use in Muslim Culture: Social and Generational Changes in Acceptance
      and Practice in Jordan.
AB  - Through narrative analysis, this paper explores the changes in acceptance of and
      response to substance use in Muslim culture by evaluating data collected in
      qualitative interviews in Jordan in 2013. What is known and unknown about
      substance use in Muslim culture throughout the Arab world from previous research
      findings provides a foundation from which to explore new perspectives and compare
      themes between younger and older generations in Jordan. Trends of social change
      and behavioral expression influenced by dramatic political and social upheaval in
      the Arab world in the last 5 years will also be evaluated for the way in which
      they may be influencing both substance use and its acceptance among young adults
      in this population. Recommendations for future research and work in this area are
      also provided based on these findings. 

PMID- 25972290
TI  - Threatened by Violence: Affective and Cognitive Reactions to Violent
      Victimization.
AB  - Stranger violence can have a variety of different physical, psychological,
      social, and economic effects on the victim. In this article, we address one
      possible impact, namely, a heightened sense of uncertainty, risk, and fear of
      violent crime. Drawing on recent advances in the psychology of risk, we make
      three contributions. First, we differentiate in our analysis between primary
      experience of violence (where the individual in question has been attacked by a
      stranger in the local streets) and secondary experience of violence (where the
      individual knows somebody who has been attacked in the local streets by a
      stranger). Second, we assess whether risk perception (beliefs about the
      likelihood, impact, and controllability of future victimization) mediates the
      empirical links between primary and secondary experience of violence and worry
      about violent crime. Finally, we examine whether victimization experience seems
      to have a greater impact on risk perception and worry among people with a high
      need for cognitive closure (who are averse to uncertainty and desire order and
      structure in their lives). Our findings indicate a number of potentially
      important mediating and moderating effects regarding the impact of stranger
      violence on fear of violent crime. We conclude with some implications for
      research and policy.

PMID- 25972291
TI  - A comparison of hydraulic architecture in three similarly sized woody species
      differing in their maximum potential height.
AB  - The physiological mechanisms underlying the short maximum height of shrubs are
      not understood. One possible explanation is that differences in the hydraulic
      architecture of shrubs compared with co-occurring taller trees prevent the shrubs
      from growing taller. To explore this hypothesis, we examined various hydraulic
      parameters, including vessel lumen diameter, hydraulic conductivity and
      vulnerability to drought-induced embolism, of three co-occurring species that
      differed in their maximum potential height. We examined one species of shrub, one
      short-statured tree and one taller tree. We worked with individuals that were
      approximately the same age and height, which was near the maximum for the shrub
      species. A number of variables correlated with the maximum potential height of
      the species. For example, vessel diameter and vulnerability to embolism both
      increased while wood density declined with maximum potential height. The
      difference between the pressure causing 50% reduction in hydraulic conductance in
      the leaves and the midday leaf water potential (the leaf's hydraulic safety
      margin) was much larger in the shrub than the other two species. In general,
      trends were consistent with understory shrubs having a more conservative life
      history strategy than co-occurring taller species. 

PMID- 25972292
TI  - Early postoperative arrhythmias after pediatric cardiac surgery.
AB  - BACKGROUND: This prospective study proposed to determine the incidence, risk
      factors, and management protocols for early postoperative arrhythmias after
      pediatric cardiac surgery, with focus on outcomes, using a uniform protocol, and
      also to see if children operated on at a later age have different issues from
      those operated on earlier. METHODS: Of 224 consecutive pediatric patients
      undergoing cardiac surgery from September 2013 to July 2014, 24 were excluded
      because their procedures were performed without cardiopulmonary bypass. RESULTS:
      The median age was 24 months (mean 50.1 +/- 62.4 months, range 0.5-216 months).
      Fifteen (7.5%) patients developed arrhythmia, the most common was junctional
      ectopic tachycardia (n = 7, 46.6%) followed by supraventricular tachycardia (n =
      5, 33.3%). All junctional ectopic tachycardias occurred within 24 h of intensive
      care unit admission. Of the 7 patients with junctional ectopic tachycardia, 5
      responded to conventional measures and 2 required amiodarone infusion. There was
      a significant longer cardiopulmonary bypass time in patients with arrhythmias
      compared to those without arrhythmias. CONCLUSION: We observed a very low
      incidence of arrhythmias, particularly junctional ectopic tachycardia, after open
      heart surgery in children. Other than a longer cardiopulmonary bypass time, no
      specific predictors were identified. It appears that the cause of arrhythmias
      following pediatric cardiac surgery is multifactorial and needs further study
      with a greater number of patients.

PMID- 25972293
TI  - Which is the best graft for the right coronary artery? Response.

PMID- 25972294
TI  - Late reoperations after acute aortic dissection repair: Single-center experience.
AB  - BACKGROUND: After repair of acute type A aortic dissection, aortic complications
      can develop, and reoperations might be necessary. In our retrospective study, we
      wanted to assess early and late outcomes in this cohort of patients. METHODS:
      From September 2005 to July 2012, 21 consecutive patients previously operated on
      for acute type A aortic dissection underwent 27 redo aortic surgical procedures.
      Indications for redo procedures were: enlargement of the false lumen in the
      residual aorta (18 events), severe aortic regurgitation with or without aortic
      root dilatation (8 events), suture dehiscence and pseudoaneurysm at the proximal
      or distal aortic graft anastomosis (5 events) or at the coronary button
      anastomosis in patients who previously underwent a Bentall procedure (1 patient).
      In all cases, total or partial cardiopulmonary bypass was used. Hypothermic
      cardiocirculatory arrest was needed in 22 (81%) procedures. RESULTS: Hospital
      mortality was 3.7% (1/27), reexploration for bleeding and paraplegia rates were
      7.4% and 7.4%, respectively. Marfan patients received 3.2 procedures per patient
      vs. 1.5 in non-Marfan patients (p < 0.01). At a mean follow-up of 6.5 years, 2
      aortic events occurred: 1 aortic death, and 1 additional aortic redo surgery.
      CONCLUSIONS: When procedures are carried out on elective basis, redo aortic
      surgery can be performed in all segments of the aorta with good early and late
      outcomes. Close lifelong clinical and radiological follow-up is mandatory. After
      repair of acute type A aortic dissection, Marfan patients are more prone to
      develop late complications, with a more rapid evolution.

PMID- 25972295
TI  - Off-pump right atrial surgery: Vena caval inflow occlusion in cardiac lesions.
AB  - BACKGROUND: Vena caval inflow occlusion, despite its utility in pediatrics, is
      rarely used in adults. We report the use of inflow occlusion in adults when
      cardiopulmonary bypass is contraindicated. METHODS: Between January 1999 and July
      2014, 35 patients in 3 hospitals presented with right-sided cardiac lesions; 27
      had right-sided endocarditis with sepsis despite maximal medical therapy, the
      rest had organized sterile masses with embolic potential in the right side of the
      heart. Comorbidities included immunosuppression, malignancy, and dialysis
      dependent renal failure. Twelve patients had heparin-induced thrombocytopenia.
      Using inflow occlusion on a beating heart, tricuspid valve vegetectomy was
      performed in 23 patients, vegetectomy and tricuspid valve repair in 3, removal of
      infected pacing leads in 7, and removal of a migrated inferior vena cava filter
      in 1. Eight patients had a single 2-min period of vena caval inflow occlusion,
      and 25 had additional periods of vena caval inflow occlusion after periods of
      reperfusion. The first 23 procedures were performed through a sternotomy. Nine
      patients underwent a right minithoracotomy (redo in 2). RESULTS: There were no
      deaths. Infected patients had resolution of sepsis and improvement in respiratory
      status. Three patients had moderate tricuspid regurgitation, the rest had trivial
      to mild tricuspid regurgitation. One patient had a transient neurological deficit
      postoperatively, and one had late empyema. CONCLUSION: Removal of infective
      material, sterile masses, and retained foreign bodies can safely be performed
      under vena caval inflow occlusion when cardiopulmonary bypass is contraindicated.

PMID- 25972297
TI  - Peripheral gene expression profile of mechanical hyperalgesia induced by repeated
      cold stress in SHRSP5/Dmcr rats.
AB  - Repeated cold stress (RCS) is known to transiently induce functional disorders
      associated with hypotension and hyperalgesia. In this study, we investigated the
      effects of RCS (24 and 4  degrees C alternately at 30-min intervals during the
      day and 4  degrees C at night for 2 days, followed by 4  degrees C on the next 2
      consecutive nights) on the thresholds for cutaneous mechanical pain responses and
      on peripheral expression of "pain-related genes" in SHRSP5/Dmcr rats, which are
      derived from stroke-prone spontaneously hypertensive rats. To define genes
      peripherally regulated by RCS, we detected changes in the expression of pain
      related genes in dorsal root ganglion cells by PCR-based cDNA subtraction
      analysis or DNA microarray analysis, and confirmed the changes by RT-PCR. We
      found significantly changed expression in eight pain-related genes (upregulated:
      Fyn, St8sia1, and Tac 1; downregulated: Ctsb, Fstl1, Itpr1, Npy, S100a10). At
      least some of these genes may play key roles in hyperalgesia induced by RCS.

PMID- 25972296
TI  - Impact of Oxidative Stress Biomarkers and Carboxymethyllysine (an Advanced
      Glycation End Product) on Prostate Cancer: A Prospective Study.
AB  - OBJECTIVE: Biomarkers of oxidative stress and advanced glycation end products
      (AGE) have been linked to the development of prostate cancer, but evidence from
      human studies is scarce or controversial. METHODS: We conducted a prospective
      nested case-control study among 48 men (24 prostate cancer cases and 24 controls)
      aged 48 to 76 years at baseline. The participants of our study were a part of the
      Fernald Community Cohort. Prostate cancer cases and controls were matched
      individually on age (+/- 3 years) with a 1:1 ratio. Biomarkers included urine F2
      isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products
      (markers of global oxidation), and carboxymethyllysine (CML) (a major end-stage
      AGE). RESULTS: At baseline, cases had similar age, body mass index, proportion of
      family history of prostate cancer, history of benign prostatic hyperplasia,
      history of hypertension, history of diabetes, number of smokers, and plasma
      glucose levels compared with controls. Levels of plasma CML were significantly
      higher in cases than in controls (182 vs. 152 MUg/mL, P < .05). In the
      conditional logistic regression model, an increase in CML equivalent to 1
      standard deviation was associated with an increased risk of incident prostate
      cancer (relative risk, 1.79; 95% confidence interval, 1.00-3.21) and accounted
      for approximately 8% variance of prostate cancer liability. Urine F2-isoprostanes
      and plasma fluorescent oxidation products were not associated with prostate
      cancer incidence. CONCLUSIONS: Higher levels of plasma CML were associated with
      increased risk of prostate cancer. This suggests a potential new pathway for
      prostate cancer prediction and treatment.

PMID- 25972298
TI  - Forming a consensus opinion on exercise prehabilitation in elderly colorectal
      cancer patients: a Delphi study.
AB  - BACKGROUND: There is no consensus amongst colorectal surgeons as to whether
      preoperative exercise is beneficial in the management of colorectal cancer
      patients. Research has shown higher rates of postoperative complications in
      patients who are less fit. Agreement needs to be sought on whether improving
      fitness via exercise should be a part of preoperative care. The Delphi process is
      an iterative process designed to refine opinions on a subject, until consensus
      agreement is reached within an expert group. METHODS: We performed a Delphi
      survey with a group of consultant colorectal surgeons. Statements achieving >80%
      agreement were taken as consensus, those achieving >80% disagreement were
      removed, and those in between were revised in the following round. The process
      ended with a group of statements which achieved consensus. RESULTS: Thirty-two
      statements were included in the first round of the survey. After three rounds of
      the survey, 21 statements were accepted as consensus, six statements were
      rejected, and seven statements did not reach consensus. It was agreed that
      exercise training should form part of preoperative care and would be supported by
      surgeons. That suitable programmes pose significant risk to patients was
      rejected. There was no consensus reached on the strength of current available
      evidence or whether it would be possible to deliver exercise programmes.
      CONCLUSIONS: This work is the first to produce a set of statements on which
      expert consensus opinion has been agreed regarding preoperative exercise in
      colorectal cancer patients. Future work, informed by this study, will design
      interventions to produce rapid improvements in fitness before surgery.

PMID- 25972300
TI  - Long-term decline in grassland productivity driven by increasing dryness.
AB  - Increasing aridity and drought severity forecast for many land areas could reduce
      the land carbon (C) sink. However, with limited long-term direct measures, it is
      difficult to distinguish direct drying effects from counter effects of CO2
      enrichment and nitrogen (N) deposition. Here, we document a >50% decline in
      production of a native C3 grassland over four decades and assign the forcing and
      timing to increasing aridity and specifically to declining late-summer rainfall.
      Analysis of C and N stable isotopes in biomass suggests that enhanced water use
      efficiency via CO2 enrichment may have slightly ameliorated the productivity
      decline but that changes in N had no effects. Identical declines in a long-term
      snow-addition experiment definitively identified increasing late-summer dryness
      as the cause. Our results demonstrate lasting consequences of recent climate
      change on grassland production and underscore the importance of understanding
      past climate-ecosystem coupling to predicting future responses to changing
      climate. 

PMID- 25972299
TI  - Bioelectrical function and structural assessment of the retina in patients with
      early stages of Parkinson's disease (PD).
AB  - PURPOSE: To determine bioelectrical function and structural changes of the retina
      in patients with early stages of Parkinson's disease (PD). MATERIALS AND METHODS:
      Thirty-eight eyes of 20 patients with early idiopathic PD and 38 eyes of 20
      healthy age- and sex-matched controls were ophthalmologically examined, including
      assessment of distance best-corrected visual acuity (DBCVA), slit lamp
      examination of the anterior and posterior segment of the eye, evaluation of the
      eye structures: paramacular retinal thickness (RT) and retinal nerve fiber layer
      (RNFL) thickness with the aid of OCT, and the bioelectrical function by full
      field electroretinogram (ERG). Additionally, PD patients were interviewed as to
      the presence of dopamine-dependent visual functions abnormalities. RESULTS: In
      patients with early PD, statistically significant changes in comparison with the
      control group were observed in ERG. They contained a reduction in mean amplitudes
      of the scotopic a-wave (rod-cone response), the scotopic oscillatory potentials
      (OPs)--OP2 and OP3, the photopic b-wave, and a reduction in the overall index
      (OP1 + OP2 + OP3) and a prolongation of mean peak times of the scotopic OP1, OP2,
      OP3, OP4 (p < 0.05). A questionnaire concerning abnormalities of dopamine
      dependent visual functions revealed that PD patients with abnormal peak times of
      OP1, OP2, and OP3 reported non-specific visual disturbances more frequently in
      comparison with PD patients with normal peak times of OPs. Other analyzed
      parameters of ERG, DBCVA, RT, and RNFL did not significantly differ between
      patients with PD and the control group. CONCLUSION: In patients with early PD,
      bioelectrical dysfunction of the retina was observed in the ERG test, probably as
      a result of dopamine deficiency in the retina. The results of our study indicate
      that ERG may also be a useful tool for understanding the reason for non-specific
      visual disturbances occurring in PD patients.

PMID- 25972302
TI  - Adenosine testing after second-generation cryoballoon ablation (ATSCA) study
      improves clinical success rate for atrial fibrillation.
AB  - AIMS: Adenosine administration after pulmonary vein (PV) isolation using
      radiofrequency, laser, and cryoablation can cause acute recovery of conduction to
      the PVs and predict atrial fibrillation (AF) recurrence. This study evaluates
      whether ablation of dormant potentials post-adenosine administration following
      second-generation cryoballoon (CB-2G) ablation may improve the success rate for
      AF. METHODS AND RESULTS: In 45 of 90 patients after a waiting period of 30 min, a
      bolus 15-21 mg of adenosine was administered followed by rapid saline flush. The
      response was assessed for each PV using a circular octapolar catheter. If needed,
      further ablation using a cryoballoon and/or cryocatheter was performed until no
      reconduction was observed after repeat adenosine administration. The remaining 45
      patients did not receive adenosine after the procedure. Acute PV isolation was
      achieved in 352 of 358 PVs (98.3%) of 86 of 90 patients (95.6%) using CB-2G. The
      adenosine group showed dormant reconduction in 5 of 45 patients (11%), 8 of 179
      PVs (4.5%), including 1 left superior pulmonary vein, 3 left inferior pulmonary
      vein, 1 right superior pulmonary vein, and 3 right inferior pulmonary vein. The
      success rate for adenosine and without adenosine group was 84 and 79%,
      respectively, after a mean follow-up of 397 +/- 47 and 349 +/- 66 days, without
      any AF recurrence in patients in whom adenosine-induced dormant conduction was
      ablated. CONCLUSION: Adenosine testing after second-generation cryoballoon
      ablation study showed that reablation of initially isolated PVs increases the
      clinical success rate for AF.

PMID- 25972301
TI  - The ratio of the neutrophil leucocytes to the lymphocytes predicts the outcome
      after cardiac resynchronization therapy.
AB  - AIMS: The low lymphocyte counts and high neutrophil leucocyte fractions have been
      associated with poor prognosis in chronic heart failure. We hypothesized that the
      baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would
      predict the outcome of chronic heart failure patients undergoing cardiac
      resynchronization therapy (CRT). METHODS AND RESULTS: The qualitative blood
      counts and the serum levels of N-terminal of the prohormone brain natriuretic
      peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy
      controls were analysed prospectively in this observational study. The 2-year
      mortality was considered as primary endpoint and the 6-month reverse remodelling
      (>=15% decrease in the end-systolic volume) as secondary endpoint. Multivariable
      regression analyses were applied and net reclassification improvement (NRI) and
      integrated discrimination improvement (IDI) were calculated. The NL ratio was
      elevated in chronic heart failure patients when compared with the healthy
      controls [2.93 (2.12-4.05) vs. 2.21 (1.64-2.81), P < 0.0001]. The baseline NL
      ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n =
      63, odds ratio = 0.38 (0.17-0.85), P = 0.01; NRI = 0.49 (0.14-0.83), P = 0.005;
      IDI = 0.04 (0.00-0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio
      = 2.44 (1.04-5.71), P = 0.03; NRI = 0.63 (0.24-1.01), P = 0.001; IDI = 0.04 (0.00
      0.08), P = 0.02] independently of the NT-proBNP levels or other factors.
      CONCLUSION: The NL ratio is elevated in chronic heart failure and predicts
      outcome after CRT. According to the reclassification analysis, 4% of the patients
      would have been better categorized in the prediction models by combining the NT
      proBNP with the NL ratio. Thus, a single blood count measurement could facilitate
      the optimal patient selection for the CRT.

PMID- 25972303
TI  - Fatigue trajectories during the first 8 months after breast cancer diagnosis.
AB  - PURPOSE: The objective of this study was to identify distinct groups of fatigue
      trajectories among women with breast cancer and to evaluate whether age, anxiety
      symptoms, physical activity, and type of treatment were associated with belonging
      to the most adverse fatigue group. METHODS: Women scheduled for breast cancer
      surgery at Copenhagen University Hospital, Denmark, were consecutively invited to
      participate in the study (n = 424), resulting in 290 women included in the
      analyses. Semiparametric group-based mixture modeling was used to identify
      distinct trajectories of fatigue assessed the week before surgery and 4 and 8
      months later. Logistic regression analysis was used to evaluate differences in
      the distinct fatigue groups. RESULTS: Two distinct groups of fatigue trajectories
      were identified. One group (21 %) had a high mean level, while the second group
      (79 %) had a low mean level of fatigue throughout the study. In multivariate
      analyses, sedentary physical activity (OR 5.78; 95 % CI 1.41-23.75), low physical
      activity (OR 3.17; 95 % CI 1.15-8.74), and increasing anxiety symptoms (OR 1.23;
      95 % CI 1.14-1.33) before surgery were significantly associated with being in the
      high-fatigue group. CONCLUSIONS: The results show that one-fifth of women with
      breast cancer experience continuously high fatigue up to 8 months after surgery
      and may have been more anxious and physically inactive. This knowledge is
      important in targeting interventions to women with fatigue throughout their
      treatment and who do not return to a low fatigue level with existing treatment,
      self-management, or support.

PMID- 25972304
TI  - Technical note: unsafe rectal temperature measurements due to delayed warming of
      the thermocouple by using a condom. An issue concerning the estimation of the
      postmortem interval by using Henbetage's nomogram.
AB  - In some cases, in the Netherlands, an additional layer is being added to the
      thermocouple, used to measure the rectal temperature in medicolegal death
      investigations. Because of this deviation from the standard method, questions
      arose regarding the accuracy and precision of the measured temperature.
      Therefore, a cooling experiment was carried out on a round body made of agar with
      an average thermal conductivity of 0.454 W/(m  degrees C) while measuring the
      temperature with and without an additional layer around the thermocouple for
      three different starting temperatures: 36, 30, and 27  degrees C. The results
      show a significant difference between the measured values for the first 5 min
      when comparing with and without the additional layer. Further, a decrease in
      precision is present within the first minutes when using an additional layer.
      Therefore, it is concluded that it is best to measure the rectal temperature
      without an additional layer around the thermocouple and caution should be taken
      when measuring with an additional layer.

PMID- 25972305
TI  - Reversible bilateral striatal lesions following Mycoplasma pneumoniae infection
      associated with elevated levels of interleukins 6 and 8.
AB  - BACKGROUND: Reversible bilateral striatal necrosis associated with Mycoplasma
      pneumoniae (M. pneumoniae) infection is a rare neurological disease. The exact
      pathogenic mechanism remains unknown. PATIENT: We report reversible bilateral
      striatal lesions with a favorable outcome secondary to M. pneumoniae infection in
      an 8-year-old Chinese girl. Cranial MRI showed abnormal signals in bilateral
      striatum, which disappeared 8 months later. To better understand the pathogenesis
      of this encephalopathy, we examined cytokines levels in serum and cerebrospinal
      fluid from this patient. The results revealed the concentrations of interleukin-6
      and interleukin-8 increased significantly in serum (26 pg/mL and 66 pg/mL,
      respectively) and cerebrospinal fluid (122 pg/mL and 325 pg/mL, respectively),
      and were reduced markedly after the therapy. Intrathecal production of
      interleukin-6 and interleukin-8 is probably related to the pathogenesis of
      striatal lesions caused by M. pneumoniae. These cytokines may cause local
      vascular injury, and finally leading to local vascular occlusion. CONCLUSION: Our
      results suggest that interleukin-6 and interleukin-8 may play important roles in
      the pathogenesis of this disease. This is the first report to describe the role
      of cytokines in this condition and relevant literature is reviewed. Our findings
      may lead to better understanding of the pathogenesis of M. pneumoniae-associated
      striatal lesions.

PMID- 25972306
TI  - The diagnostic value of MRI in pediatric chronic inflammatory demyelinating
      polyradiculoneuropathy.

PMID- 25972307
TI  - How to estimate exposure when studying the temperature-mortality relationship? A
      case study of the Paris area.
AB  - Time series studies assessing the effect of temperature on mortality generally
      use temperatures measured by a single weather station. In the Paris region, there
      is a substantial measurement network, and a variety of exposure indicators
      created from multiple stations can be tested. The aim of this study is to test
      the influence of exposure indicators on the temperature-mortality relationship in
      the Paris region. The relationship between temperature and non-accidental
      mortality was assessed based on a time series analysis using Poisson regression
      and a generalised additive model. Twenty-five stations in Paris and its three
      neighbouring departments were used to create four exposure indicators. These
      indicators were (1) the temperature recorded by one reference station, (2) a
      simple average of the temperatures of all stations, (3) an average weighted on
      the departmental population and (4) a classification of the stations based on
      land use and an average weighted on the population in each class. The relative
      risks and the Akaike criteria were similar for all the exposure indicators. The
      estimated temperature-mortality relationship therefore did not appear to be
      significantly affected by the indicator used, regardless of study zone
      (departments or region) or age group. The increase in temperatures from the
      90(th) to the 99(th) percentile of the temperature distribution led to a
      significant increase in mortality over 75 years (RR = 1.10 [95% CI, 1.07; 1.14]).
      Conversely, the decrease in temperature between the 10(th) and 1(st) percentile
      had a significant effect on the mortality under 75 years (RR = 1.04 [95% CI,
      1.01; 1.06]). In the Paris area, there is no added value in taking multiple
      climatic stations into account when estimating exposure in time series studies.
      Methods to better represent the subtle temperature variations in densely
      populated areas in epidemiological studies are needed.

PMID- 25972309
TI  - Valuable features in mobile health apps for patients and consumers: content
      analysis of apps and user ratings.
AB  - BACKGROUND: The explosion of mobile phones with app capabilities coupled with
      increased expectations of the patient-consumers' role in managing their care
      presents a unique opportunity to use mobile health (mHealth) apps. OBJECTIVES:
      The aim of this paper is to identify the features and characteristics most-valued
      by patient-consumers ("users") that contribute positively to the rating of an
      app. METHODS: A collection of 234 apps associated with reputable health
      organizations found in the medical, health, and fitness categories of the Apple
      iTunes store and Google Play marketplace was assessed manually for the presence
      of 12 app features and characteristics. Regression analysis was used to determine
      which, if any, contributed positively to a user's rating of the app. RESULTS:
      Analysis of these 12 features explained 9.3% (R(2)=.093 n=234, P<.001) of the
      variation in an app's rating, with only 5 reaching statistical significance. Of
      the 5 reaching statistical significance, plan or orders, export of data,
      usability, and cost contributed positively to a user's rating, while the tracker
      feature detracted from it. CONCLUSIONS: These findings suggest that users
      appreciate features that save time over current methods and identify an app as
      valuable when it is simple and intuitive to use, provides specific instructions
      to better manage a condition, and shares data with designated individuals.
      Although tracking is a core function of most health apps, this feature may
      detract from a user's experience when not executed properly. Further
      investigation into mHealth app features is worthwhile given the inability of the
      most common features to explain a large portion of an app's rating. In the
      future, studies should focus on one category in the app store, specific diseases,
      or desired behavior change, and methods should include measuring the quality of
      each feature, both through manual assessment and evaluation of user reviews.
      Additional investigations into understanding the impact of synergistic features,
      incentives, social media, and gamification are also warranted to identify
      possible future trends.

PMID- 25972308
TI  - The impact of temperature on mortality in a subtropical city: effects of cold,
      heat, and heat waves in Sao Paulo, Brazil.
AB  - Understanding how weather impacts health is critical, especially under a changing
      climate; however, relatively few studies have investigated subtropical regions.
      We examined how mortality in Sao Paulo, Brazil, is affected by cold, heat, and
      heat waves over 14.5 years (1996-2010). We used over-dispersed generalized linear
      modeling to estimate heat- and cold-related mortality, and Bayesian hierarchical
      modeling to estimate overall effects and modification by heat wave
      characteristics (intensity, duration, and timing in season). Stratified analyses
      were performed by cause of death and individual characteristics (sex, age,
      education, marital status, and place of death). Cold effects on mortality
      appeared higher than heat effects in this subtropical city with moderate climatic
      conditions. Heat was associated with respiratory mortality and cold with
      cardiovascular mortality. Risk of total mortality was 6.1% (95% confidence
      interval 4.7, 7.6%) higher at the 99th percentile of temperature than the 90th
      percentile (heat effect) and 8.6% (6.2, 11.1%) higher at the 1st compared to the
      10th percentile (cold effect). Risks were higher for females and those with no
      education for heat effect, and males for cold effect. Older persons, widows, and
      non-hospital deaths had higher mortality risks for heat and cold. Mortality
      during heat waves was higher than on non-heat wave days for total,
      cardiovascular, and respiratory mortality. Our findings indicate that mortality
      in Sao Paulo is associated with both cold and heat and that some subpopulations
      are more vulnerable.

PMID- 25972310
TI  - Recombinant soluble thrombomodulin for postoperative disseminated intravascular
      coagulation.
AB  - BACKGROUND: Thrombomodulin is a thrombin receptor on the endothelial cell surface
      that plays an important role in the regulation of intravascular coagulation. The
      purpose of this study was to evaluate the efficacy and safety of treatment with
      recombinant human soluble thrombomodulin (rhTM) for patients with septic
      disseminated intravascular coagulation (DIC) associated with gastroenterological
      surgery. MATERIALS AND METHODS: From April 2011-September 2013, 201 patients with
      DIC associated with gastroenterological surgery were treated in 16 institutions
      in Kumamoto, Japan. The patients were diagnosed according to the Japanese
      Association for Acute Medicine DIC scoring system. The clinical course, mortality
      rate at 28 d, and adverse events were evaluated retrospectively. RESULTS: Forty
      five patients were excluded because they did not meet the Japanese Association
      for Acute Medicine DIC criteria or had an insufficient duration of drug
      administration. Thus, 156 patients were analyzed. Of these patients, 107 received
      rhTM at the discretion of the attending surgeon and 49 did not. The most common
      reason for surgery in both groups was peritonitis due to perforation of the
      colon. Within 7 d, the platelet count, prothrombin time-international normalized
      ratio, DIC score, neutrophil count, and C-reactive protein level significantly
      improved in the rhTM group compared with those in the control. Treatment with
      rhTM was significantly associated with reduced inhospital mortality at 28 d. The
      incidence of adverse events did not differ between the two groups. CONCLUSIONS:
      Therapy with rhTM may be associated with reduced inhospital mortality in patients
      with septic DIC associated with gastroenterological surgery without increasing
      adverse events.

PMID- 25972311
TI  - Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and
      phosphoinositide 3-kinase gamma mediate the anti-inflammatory effects of
      magnesium sulfate.
AB  - BACKGROUND: We previously demonstrated that inhibiting phosphoinositide 3-kinase
      (PI3K) or activating L-type calcium channels blocked the anti-inflammatory
      effects of magnesium sulfate (MgSO4). However, the question as which class I PI3K
      isoform (PI3Kalpha, PI3Kbeta, PI3Kdelta, or PI3Kgamma) is involved in this regard
      remains unstudied. The question as whether MgSO4 and L-type calcium channels
      interact to influence PI3K activation also remains unstudied. We therefore
      designed this study to test two hypotheses: (1) inhibiting PI3Kalpha, PI3Kbeta,
      PI3Kdelta, or PI3Kgamma would block the anti-inflammatory effects of MgSO4 and
      (2) activating L-type calcium channels would block the effects of MgSO4 on
      activating PI3K. MATERIALS AND METHODS: PI3K isoform investigation: macrophages
      (RAW264.7 cells) were treated with endotoxin, endotoxin plus MgSO4, or endotoxin
      plus MgSO4 plus the selective inhibitor of PI3Kalpha (PIK-75), PI3Kbeta (TGX
      221), PI3Kdelta (IC-87114), or PI3Kgamma (AS-252424). Calcium channel
      investigation: macrophages were treated with endotoxin, endotoxin plus MgSO4, or
      endotoxin plus MgSO4 plus the L-type calcium channel activator BAY-K8644.
      RESULTS: The endotoxin plus MgSO4 group presented lower concentrations of
      inflammatory mediators (macrophage inflammatory protein 2, tumor necrosis factor
      alpha, and interleukin 6, lower nuclear concentration of phosphorylated nuclear
      factor kappaB, lower cytosolic concentration of phosphorylated inhibitor
      kappaBalpha, and higher concentration of phosphorylated Akt (PI3K activation
      marker) than the endotoxin group (all P < 0.05). These effects of MgSO4 were
      significantly reduced by TGX-221, IC-87114, or AS-252424, but not PIK-75.
      Additionally, BAY-K8644 blocked the effect of MgSO4 on activating PI3K.
      CONCLUSIONS: MgSO4 exerts its anti-inflammatory effects through activating
      PI3Kbeta, PI3Kdelta, and PI3Kgamma. The underlying mechanism appears to involve
      inhibition of L-type calcium channels.

PMID- 25972312
TI  - Pyloric stenosis--postoperative care on a nonsurgical ward.
AB  - BACKGROUND: Recent progress has been made in the care of infants with
      hypertrophic pyloric stenosis (HPS), including earlier operative intervention and
      shorter hospital length of stay (LOS), which is attributable to expedited
      postoperative feeding protocols developed and implemented by surgeons. We
      hypothesized that patients with HPS admitted to a unit that is co-managed by
      nonsurgeon providers postoperatively have a longer LOS than those on the surgical
      ward. MATERIALS AND METHODS: We reviewed the medical records of infants who
      underwent pyloromyotomy for HPS at a single institution from April, 2009-July,
      2013. RESULTS: A total of 259 patients underwent pyloromyotomy (35 female;
      13.5%), 205 (79%) were admitted to the surgical ward; 46 had a planned neonatal
      intensive care unit (NICU) admission (18%) and were co-managed with the
      neonatology team. Eight (3%) had an unplanned NICU admission and were excluded
      from the analysis. The groups did not differ in terms of sex, age, serum
      electrolytes at presentation, or time between surgeon evaluation and operative
      intervention. Surgical ward patients had longer preoperative symptom duration.
      Operative time was longer in the NICU patients. Comparing the two groups, there
      was no difference in postoperative apnea, hypoxic, or bradycardic episodes. NICU
      patients achieved ad libitum feeds later than floor patients (2.0 versus 1.4 d; P
      = 0001) and had a longer postoperative LOS (2.2 versus 1.6 d; P = 0.0012).
      CONCLUSIONS: Patients with HPS admitted to the NICU postoperatively had a longer
      time to full feeds and hospital LOS. The reduction in LOS between hospital wards
      may be improved with implementation of a hospital-wide postoperative protocol for
      patients with HPS.

PMID- 25972313
TI  - Severe acute pancreatitis in the community: confusion reigns.
AB  - BACKGROUND: The management of acute pancreatitis (AP) has evolved through
      enhanced understanding of the disease. Despite several evidence-based practice
      guidelines for AP, our hypothesis is that many hospitals still use historical
      treatments rather than adhere to the current guidelines, which have demonstrated
      shorter hospital stays, decreased infectious complications, decreased morbidity,
      and decreased mortality. MATERIALS AND METHODS: Seventy-eight patients
      transferred to our institution with AP from 2010-2014 were retrospectively
      studied to compare pretransfer versus posttransfer adherence to current practice
      guidelines. Primary measures included use of antibiotics (abx), enteral
      nutrition, drainage of asymptomatic pseudocysts, and interventions for necrosis
      in the early phase (<4 wk). RESULTS: Pretransfer, abx were given to 51 patients;
      however, posttransfer, abx were discontinued in 33 patients and started in 6
      patients within 24 h of admission (pretransfer versus posttransfer abx, 51 versus
      24, P < 0.001). Empiric abx for AP were used in 36 patients pretransfer versus 9
      patients posttransfer (P < 0.001). Patients were initially nil per os or on total
      parenteral nutrition in 89%; this was reduced to 17% within 72 h by starting a
      diet or enteric feeds (pretransfer versus posttransfer feeding, 9 versus 65
      patients, P < 0.001). Fifteen transfer patients had pseudocysts that were
      believed to "require drainage"; five patients received intervention but >4 wk
      from initial episode of AP. Pretransfer, five patients had pancreatic debridement
      in the early phase, which resulted in prolonged postoperative length of stay
      compared with eight patients requiring debridement, which were delayed (early
      versus late, 56 versus 16 d, P < 0.05). CONCLUSIONS: There is still great
      confusion in the treatment of AP in community hospitals. Primary principles in
      the care of these patients are not routinely followed despite established
      guidelines. Increased dissemination is required to prevent lengthy
      hospitalizations and long-term morbidity.

PMID- 25972314
TI  - Video recording of the operating room--is anonymity possible?
AB  - BACKGROUND: Video recording in the operating room (OR) has many potential
      applications for research, quality improvement, and education. Routine video
      recording is limited by patient and staff privacy concerns, but this may be
      overcome by creating videos that are deidentified but still retain sufficient
      video data for intended applications. It is unknown what effect video processing
      may have on staff perceptions of identifiability in video recordings; this study
      was designed to investigate this effect. METHODS: We presented OR staff members
      with short clips of the same staged surgical procedure, each representing
      different data formats or processing (unaltered video, blurred faces, infrared,
      and point clouds). Staff rated each video on a Likert scale (1 = anonymous, "no
      one could identify me"; 10 = not anonymous, "it would be easy to identify me) and
      provided qualitative comments. RESULTS: Eighty-three staff members agreed to
      participate. The mean response for the unaltered, blurred faces, infrared, and
      point cloud videos were 7.05, 3.75, 5.77, and 1.41, respectively (all P < 0.001),
      demonstrating that postprocessing methods impact perceived anonymity. Staff roles
      (surgeons versus anesthesiologists versus nurses) were not significantly
      associated perceptions of identifiability (P >= 0.16). CONCLUSIONS: This study
      demonstrates that surgical video postprocessing affects OR staff members'
      perceptions of anonymity and that it is possible to produce videos that retain
      details about surgical activity while still being perceived as anonymous. These
      findings are highly relevant to any study that uses video for quality improvement
      or health care research by providing the first normative data on
      "deidentification."

PMID- 25972315
TI  - More fateful than fruitful? Intracranial pressure monitoring in elderly patients
      with traumatic brain injury is associated with worse outcomes.
AB  - BACKGROUND: In an expanding elderly population, traumatic brain injury (TBI)
      remains a significant cause of death and disability. Guidelines for management of
      TBI, according to the Brain Trauma Foundation (BTF), include intracranial
      pressure (ICP) monitoring. Whether ICP monitoring contributes to outcomes in the
      elderly patients with TBI has not been explored. METHODS: This is a retrospective
      study extracted from the National Trauma Database 2007-2008 research datasets.
      Patients were included if aged >55 y and they met BTF indications for ICP
      monitoring. Patients that had nonsurvivable injuries (any body region,
      abbreviated injury score = 6), were dead on arrival, had withdrawal of care, or
      length of stay <48 h were excluded. Outcomes were then stratified based on ICP
      monitoring. The primary outcomes were inhospital mortality and favorable
      discharge. Logistic regression was used to analyze the effect of ICP monitoring
      on outcomes. RESULTS: A total of 4437 patients were included with 11.2% having an
      ICP monitor placed. Patients requiring an ICP monitor were younger overall, more
      likely to present hypertensive, had higher injury severity, and more likely to
      require operative intervention. Median initial Glasgow coma scale (3) was similar
      between groups. Of those patients with ICP monitoring, overall mortality was
      significantly higher, and they were less likely to have favorable discharge
      status. Craniotomy itself was not associated with increased mortality (P =
      0.450). CONCLUSIONS: Our findings suggest that the use of ICP monitoring
      according to BTF guidelines in elderly TBI patients does not provide outcomes
      superior to treatment without monitoring. The ideal group to benefit from ICP
      monitor placement remains to be elucidated.

PMID- 25972316
TI  - UK scientists reject call for moratorium on gene editing.

PMID- 25972317
TI  - Diagnostic microbiology: the accelerating transition from culture-based to
      molecular-based methods.

PMID- 25972318
TI  - Molecular pathology of hereditary and sporadic medullary thyroid carcinomas.
AB  - OBJECTIVES: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of
      thyroid malignancy, with unique histologic features and molecular pathology. It
      is important to recognize, because its management, which is in part driven by the
      genetic basis of this disease, is different from follicular-derived thyroid
      tumors. The aim of this article is to briefly review the histopathologic features
      of MTC and then explore its molecular pathology, including the role of molecular
      diagnostic testing and the use of targeted therapy for advanced disease. METHODS:
      A review of published literature was performed. RESULTS: A subset of MTC cases is
      hereditary and due to germline mutations in the RET tyrosine kinase receptor
      gene. Somatic mutations in either RET or RAS are also present in most sporadic
      tumors. CONCLUSIONS: Molecular genetic testing is routinely performed to identify
      hereditary cases. In addition, understanding the molecular basis of both
      hereditary and sporadic MTC has led to the development of targeted therapy with
      tyrosine kinase inhibitors. Although additional data are needed, tumor mutation
      status may affect response to targeted therapy. Therefore, it is possible that
      genetic testing of tumor tissue to predict treatment response, as is currently
      done for other cancer types, may come into practice in the future.

PMID- 25972319
TI  - KRAS Mutations in Mucinous Lesions of the Uterus.
AB  - OBJECTIVES: The current study examined the KRAS mutation status in a spectrum of
      mucinous lesions of the uterus, including mucinous metaplasia (MM), atypical
      mucinous proliferation (AMP), endocervical mucosa, and microglandular hyperplasia
      (MGH). METHODS: Thirty-nine cases, including 15 AMPs, nine MMs, nine MGHs, and
      six normal endocervical mucosas, were selected from the departmental archive. All
      AMP cases with follow-up biopsies or hysterectomies were reviewed. Genomic DNA
      was extracted from formalin-fixed, paraffin-embedded tissue and KRAS codons 12
      and 13 sequence analyzed. RESULTS: KRAS codon 12 and 13 mutations were detected
      in 10 (67%) of the 15 AMP cases. No KRAS mutations were identified in MMs, MGHs,
      and endocervical mucosas (P = .002, AMP vs MM or MGH, Fisher exact test). Most
      women with AMP were postmenopausal (13/15 [86.7%]) and presented with
      dysfunctional uterine bleeding. Among the 10 cases of AMP harboring KRAS
      mutations, six (60%) cases were subsequently diagnosed with carcinoma, one with
      atypical complex hyperplasia, and two with AMP within endometrial polyps.
      CONCLUSIONS: The results suggest a possible association between KRAS mutations
      and mucinous differentiation in endometrial carcinogenesis. KRAS status can help
      in assessing benign from precursor or malignant mucinous lesions as well as
      differentiate endometrial lesions from those of cervical origin.

PMID- 25972320
TI  - Flow cytometric identification of immunophenotypically aberrant T-cell clusters
      on skin shave biopsy specimens from patients with mycosis fungoides.
AB  - OBJECTIVES: To assess the ability of flow cytometry (FC) to detect putative
      neoplastic T-cell subsets on skin shave biopsy (SSB) specimens from patients with
      mycosis fungoides (MF) and to study the immunophenotype of skin-infiltrating
      tumor cells in MF. METHODS: SSB specimens from patients with suspected MF were
      bisected and submitted for both FC and routine histopathology. Six-dimensional
      gating strategies were applied to identify putative neoplastic cells,
      independently from their expected immunophenotype. RESULTS: Aberrant T cells were
      detected by FC in 18 of 33 SBB specimens, of which all had clinicomorphologic
      features of MF. Of the remaining 15 SSB specimens, six had clinicomorphologic
      features of MF and nine were diagnosed with benign inflammatory dermatoses.
      Unexpectedly, CD26 was aberrantly overexpressed in 11 (73%) and lost in three
      (20%) of 15 SSB specimens from patients with MF where this antigen was evaluated.
      Other detected aberrancies included CD3 dim- (13/18 [72%]), CD7 dim- (15/18
      [83%]), and CD4-/CD8- (3/18 [17%]). CONCLUSIONS: FC is capable of identifying
      putative neoplastic cells on SSB specimens from patients with MF. Bright
      homogeneous CD26 expression is a common and previously undescribed
      immunophenotypic aberrancy on MF skin infiltrates.

PMID- 25972321
TI  - Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow:
      paratrabecular involvement as an important distinguishing feature.
AB  - OBJECTIVES: The differential diagnosis between bone marrow involvement by
      lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) is challenging
      because histology and immunophenotype of both diseases overlap. We revisited the
      diagnostic pathology features of both diseases in the bone marrow. METHODS: We
      studied a series of bone marrow trephine biopsy specimens from 59 patients with
      Waldenstrom macroglobulinemia without extramedullary involvement and bone marrow
      biopsy specimens from 23 patients with well-characterized MZL who also had bone
      marrow involvement. H&E- and immunoperoxidase-stained sections of bone marrow
      trephine biopsy specimens as well as flow cytometry and classic cytogenetics
      performed on aspirations were reviewed. The study was complemented with MYD88
      L265P mutation analysis of all samples. RESULTS: The most distinguishing features
      of LPL with respect to MZL were focal paratrabecular involvement (P < .001), the
      presence of lymphoplasmacytoid cells (P < .001) and Dutcher bodies (P < .001),
      increased numbers of mast cells (P < .001), and the MYD88 L265P mutation (P <
      .001). CONCLUSIONS: LPL can be reliably distinguished from MZL in the bone marrow
      by using a combination of pathology characteristics. Our findings stress the
      diagnostic importance of using the combination of the following parameters for a
      correct LPL diagnosis: paratrabecular infiltration, the presence of
      lymphoplasmacytoid cells and cells with Dutcher bodies, and an increased number
      of mast cells in addition to the presence of MYD88 mutation.

PMID- 25972322
TI  - Consultative issues in surgical neuropathology: a retrospective review of the
      rationale for submitting cases for expert review.
AB  - OBJECTIVES: Second opinions on neuropathology cases are sought for a variety of
      reasons. We investigated the rationales for seeking expert neuropathologic
      review. METHODS: A retrospective review was done of the correspondence
      accompanying neuropathology cases submitted over a 5-year period. The review used
      a taxonomy of referral reasons, the submitting diagnoses, and requests for
      ancillary tests. RESULTS: In total, 508 adult cases were submitted, including
      glioblastoma (n = 94), anaplastic astrocytoma (n = 49), low-grade glioma (n =
      49), oligodendroglioma (n = 48), and pituitary adenoma (n = 12). Thirty-nine
      cases submitted requested ancillary testing. A taxonomy of four categories
      revealed the following: preliminary diagnosis (n = 228 cases) was the most common
      reason for requesting review, followed by no diagnosis rendered (n = 183 cases),
      second opinion (n = 53), and confirmation/quality assurance (n = 43); the
      remaining case was "other." Overall, 456 cases were submitted by pathologists, 40
      by clinicians and 12 by patients. CONCLUSIONS: Pathologists who predominately
      submit cases with a preliminary diagnosis rendered seek expert consultation while
      clinicians seek a second opinion.

PMID- 25972323
TI  - Osteopontin Regulates VEGFA and ICAM-1 mRNA Expression in Breast Carcinoma.
AB  - OBJECTIVES: To analyze the regulatory role of osteopontin on biomarkers
      associated with cell survival, invasiveness, and angiogenesis mechanisms in a
      clinical series and breast cancer cell lines. METHODS: We analyzed by
      quantitative real-time polymerase chain reaction the messenger RNA (mRNA)
      expression of osteopontin, Bcl2, intercellular adhesion molecule 1 (ICAM-1), and
      vascular endothelial growth factor A (VEGFA) in several breast cancer cell lines
      and in 148 breast carcinomas classified into intrinsic subtypes. RESULTS: We
      found coexpression of osteopontin, Bcl2, ICAM-1, and VEGFA in triple-negative MDA
      MB-468 and MDA-MB-231 cell lines. Furthermore, osteopontin silencing by small
      interfering RNA inhibited ICAM-1 and VEGFA expression and cell proliferation in
      MDA-MB-468 cells. In breast cancer specimens, we found a positive correlation
      between osteopontin, ICAM-1, and VEGFA mRNA expression, especially in triple
      negative/basal-like tumors. Among patients with osteopontin-overexpressing
      tumors, VEGFA remained an independent prognostic indicator for recurrence (hazard
      ratio, 2.95; 95% confidence interval [CI], 1.48-5.87; P = .002) and death (hazard
      ratio, 3.25; 95% CI, 1.48-7.11; P = .003) (multivariate analysis, Cox
      regression). CONCLUSIONS: Our results support that osteopontin regulates ICAM-1
      and VEGFA expression mainly in triple-negative/basal-like breast carcinomas,
      suggesting a relevant role in the pathogenesis and tumor progression of this
      molecular subtype. Moreover, VEGFA mRNA levels showed an independent prognostic
      value in patients with breast cancer.

PMID- 25972324
TI  - Differential diagnostic value of "blue reticulated chondroid-like material" in
      aneurysmal bone cysts: a classic histopathologic analysis of 215 cases.
AB  - OBJECTIVES: Our classic histopathologic study of aneurysmal bone cyst (ABC)
      revealed that "blue reticulated chondroid-like material" (BRC) is characteristic
      of ABC. METHODS: The light microscopic findings were retrospectively analyzed in
      215 cases of ABC, including 101 primary and 114 secondary cases. In addition, 22
      cases of telangiectatic osteosarcoma (TOS) were drawn from the same source and
      used as a control. RESULTS: We found the presence of typical BRC in 24 (23.8%) of
      101 cases of primary ABC and in six (5.3%) of 114 cases of secondary ABC, with an
      overall incidence of 30 (14%). None of the cases of TOS showed BRC. BRC was
      significantly more common in primary ABC than in secondary ABC (P < .05) and in
      patients 19 years or younger than in those 20 years or older (P < .05).
      CONCLUSIONS: BRC appears to be a unique histopathologic feature of ABC, making it
      valuable to differentiate benign ABC from TOS. Simple H&E stain can be
      economically performed anywhere.

PMID- 25972325
TI  - p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma
      From Mesothelial Hyperplasia and Epithelial Ovarian Cancer.
AB  - OBJECTIVES: It can be difficult to differentiate diffuse malignant peritoneal
      mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal
      dissemination of gynecologic malignancies, such as epithelial ovarian cancer
      (EOC), which cause a large amount of ascites. Detection of the homozygous
      deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an
      effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of
      this study was to investigate the ability of the p16 FISH assay to differentiate
      DMPM from RMH and EOC. METHODS: p16 FISH was performed in 28 DMPMs (successful in
      19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10%
      for homozygous deletion and more than 40% for heterozygous deletion. RESULTS:
      According to the above criteria, nine (47.4%) of 19 successful DMPM cases were
      homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion
      positive, whereas all RMH cases were negative for the p16 deletion. In all four
      major histologic subtypes of EOC, neither p16 homozygous nor heterozygous
      deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity
      of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%.
      CONCLUSIONS: Our study suggests that p16 FISH analysis is useful in
      differentiating DMPM from RMH and EOC when homozygous deletion is detected.

PMID- 25972326
TI  - Salivary gland tumor fine-needle aspiration cytology: a proposal for a risk
      stratification classification.
AB  - OBJECTIVES: Fine-needle aspiration (FNA) is useful in the evaluation of salivary
      gland tumors, but currently no standard terminology or risk stratification model
      exists. METHODS: FNA smears were reviewed and categorized based on cytonuclear
      features, stromal characteristics, and background characteristics. Risk of
      malignancy was calculated for each category. Classifications as benign, neoplasm
      of uncertain malignant potential (NUMP), suspicious for malignancy, and positive
      for malignancy were used to aggregate categories into similar risk groups.
      RESULTS: Categorization of salivary gland aspirates into morphologic categories
      resulted in the expected risk stratification. Grouping of categories maintained
      risk stratification, providing classes with malignancy risk as follows: benign,
      2%; NUMP, 18%; suspicious for malignancy, 76%; and positive for malignancy, 100%.
      CONCLUSIONS: Salivary gland FNA categorization into commonly encountered
      morphologic categories provides risk stratification, which translates to a
      simplified classification scheme of benign, NUMP, suspicious, and positive for
      malignancy similar to the paradigm in other organ systems.

PMID- 25972327
TI  - A case series of clinically undiagnosed hematopoietic neoplasms discovered at
      autopsy.
AB  - OBJECTIVES: In the United States, autopsy rates have diminished to less than 5%
      during the last half of the 20th century and the beginning of the 21st century
      for a multitude of reasons. Many believe this results in unrecognized
      malignancies that could have explained a patient's death. METHODS: We describe
      six deaths in which hematopoietic neoplasms were identified at autopsy but were
      not diagnosed clinically. RESULTS: The six undiagnosed hematopoietic malignancy
      cases discovered at autopsy include four men and two women ranging from 50 to 78
      years of age. One patient was African American and five patients were white, all
      with multiple comorbidities. The tumors included diffuse large B-cell lymphoma,
      activated B-cell type, intravascular large B-cell lymphoma, ALK-negative
      anaplastic large cell lymphoma arising in a setting of human immunodeficiency
      virus, and a myeloid sarcoma. CONCLUSIONS: These cases illustrate the importance
      of the traditional postmortem examination in not only confirming clinical
      diagnoses but also identifying previously unknown diagnoses. Hematologic
      malignancies may present with nonspecific clinical manifestations, and this
      series of cases also emphasizes the necessity for widening the differential
      diagnosis in patients with unexplained lactic acidosis and hepatic failure to
      include hematopoietic malignancies since prompt treatment may be lifesaving.

PMID- 25972328
TI  - Low-cost workflow improvement reduces gastrointestinal block use 17% by altering
      classic histotechnology testing.
AB  - OBJECTIVES: Gastrointestinal (GI) biopsy specimens were previously limited to
      four per cassette to facilitate established internal technical work practices and
      histotechnology best practice guidelines. We evaluated the workflow of these
      biopsy specimens. METHODS: We implemented three specific changes: (1) up to 10 GI
      biopsy specimens could be placed in each cassette, (2) histotechnologists would
      no longer orient GI biopsy specimens, and (3) embedding would be in a straight
      line rather than diagonal. We evaluated the effects of these changes on total
      block numbers, quality of slides, and perceptions of staff. RESULTS: The mean
      number of cassettes used was reduced 17% for GI biopsy cases, or an overall
      decrease of 3% of total blocks processed by our histopathology laboratory. Slide
      quality was unchanged. Staff reported increased job satisfaction. CONCLUSIONS:
      This simple, low-cost, low-effort process change yielded immediate and
      significant time savings for grossing and histology staff, increased job
      satisfaction, and challenges conventional histotechnology teaching.

PMID- 25972329
TI  - FGFR2 Assessment in Gastric Cancer Using Quantitative Real-Time Polymerase Chain
      Reaction, Fluorescent In Situ Hybridization, and Immunohistochemistry.
AB  - OBJECTIVES: Fibroblast growth factor receptor 2 (FGFR2) amplification has been
      reported to be a target for treatment in gastric cancer. However, an optimal
      tissue source and method for evaluating FGFR2 have yet to be established.
      METHODS: Copy numbers were compared by quantitative polymerase chain reaction
      (qPCR) using frozen vs formalin-fixed, paraffin-embedded (FFPE) tissue and biopsy
      vs surgical specimens. We correlated the results of qPCR and immunohistochemistry
      (IHC) with fluorescence in situ hybridization (FISH) using stage IV gastric
      cancer biopsy specimens and validated the results in surgical specimens. RESULTS:
      FFPE tissues were suitable for qPCR, and biopsy specimens were equivalent to or
      better than surgical specimens. qPCR and IHC results exhibited an excellent
      correlation with FISH at eight or more copies by qPCR in any kind of tissue, 5%
      or more by IHC in biopsy specimens, and 10% or more by IHC in surgical specimens.
      FGFR2 amplification was 6.6% in stage IV gastric cancers, and 42% of these showed
      heterogeneous amplification and overexpression. IHC indicated a good correlation
      with FISH even in the heterogeneous cases. CONCLUSIONS: FFPE biopsy tissues are
      an adequate source for FGFR2 evaluation in gastric carcinomas, and a qPCR-based
      copy number assay can be used for screening. IHC is also a valid and practical
      method for evaluating FGFR2, considering frequent heterogeneity.

PMID- 25972330
TI  - Conventional karyotyping and fluorescence in situ hybridization: an effective
      utilization strategy in diagnostic adult acute myeloid leukemia.
AB  - OBJECTIVES: Cytogenetics defines disease entities and predicts prognosis in acute
      myeloid leukemia (AML). Conventional karyotyping provides a comprehensive view of
      the genome, while fluorescence in situ hybridization (FISH) detects targeted
      abnormalities. The aim of this study was to compare the utility of karyotyping
      and FISH in adult AML. METHODS: We studied 250 adult AML cases with concurrent
      karyotyping and FISH testing. Karyotyping was considered adequate when 20 or more
      metaphases were analyzed. RESULTS: In total, 220 cases had adequate karyotyping
      and were classified as normal karyotype/normal FISH (n = 92), normal
      karyotype/abnormal FISH (n = 4), abnormal karyotype/normal FISH (n = 8), and
      abnormal karyotype/abnormal FISH (n = 116). The overall karyotype/FISH
      concordance rate was 97.7% with five discordant cases identified, four from the
      normal karyotype/abnormal FISH group and one from the abnormal karyotype/abnormal
      FISH group. No karyotype/FISH discordance was seen in the abnormal
      karyotype/normal FISH group for the FISH probes evaluated. FISH lent prognostic
      information in one (0.5%) of 220 cases with normal karyotype/abnormal FISH: CBFB
      MYH11 fusion, indicating favorable prognosis. CONCLUSIONS: In adult AML, FISH
      rarely provides additional information when karyotyping is adequate. We therefore
      propose an evidence-based, cost-effective algorithmic approach for routine
      conventional karyotype and FISH testing in adult AML workup.

PMID- 25972332
TI  - Little things make big things happen: angiolymphatic invasion and tumor necrosis
      prognosticate the outcome of locally advanced non-small cell lung cancer treated
      with a prior induction therapy.
AB  - OBJECTIVES: Size, invasion of thoracic structures, and ipsilateral mediastinal
      lymph node involvement (pN2) are well-known prognostic factors that configure the
      staging of resectable, locally advanced non-small cell lung cancer (LA-NSCLC).
      The prognostic impact of angiolymphatic invasion (ALI) and tumor necrosis (TN)
      has been barely explored in LA-NSCLC treated with prior induction therapies.
      METHODS: We retrospectively reviewed 47 resected LA-NSCLCs treated with a prior
      platin-based chemotherapy or chemoradiation. The impact of ALI, TN, and other
      pathologic features on survival was analyzed. RESULTS: ALI was presented in 23.4%
      of cases and TN in 29.8%. Disease-free and overall survival decreased when ALI,
      TN, or pN2 was present. The incidence of ALI was lower in LA-NSCLC with a good
      response to induction. CONCLUSION: Our series is the first to report the
      prognostic impact of ALI and TN in induction-treated LA-NSCLC. The presence of
      ALI and TN should be included in the pathologic reports.

PMID- 25972331
TI  - Endoscopic ultrasound fine-needle aspiration cytology mutation profiling using
      targeted next-generation sequencing: personalized care for rectal cancer.
AB  - OBJECTIVES: In an era of precision medicine, our aim was to determine the
      frequency and theranostic potential of mutations identified in malignant lymph
      nodes (LNs) sampled by endoscopic ultrasound fine-needle aspiration (EUS FNA) of
      patients with rectal cancer by targeted next-generation sequencing (NGS).
      METHODS: The NGS Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies,
      Carlsbad, CA) and MiSeq (Illumina, San Diego, CA) sequencers were used to
      sequence and assess for 2,800 or more possible mutations in 50 established cancer
      associated genes. RESULTS: Among 102 patients, 89% had 194 pathogenic alterations
      identified in 19 genes. The identification of KRAS, NRAS, or BRAF mutations
      suggests that 42% are likely nonresponders to anti-epidermal growth factor
      receptor therapy. Among KRAS, NRAS, or BRAF wild-type patients, alterations in
      eight genes linked to alternative therapies were identified in 44%. CONCLUSIONS:
      Our data demonstrate the successful ability to apply a single multiplex test to
      allow multigene mutation detection from malignant LN cytology specimen DNA
      collected by EUS FNA.

PMID- 25972333
TI  - Characteristics and Antibiotic Use Associated With Short-Term Risk of Clostridium
      difficile Infection Among Hospitalized Patients.
AB  - OBJECTIVES: Polymerase chain reaction (PCR) has been shown to have an excellent
      sensitivity and specificity for the detection of Clostridium difficile infection
      (CDI). Little is known about risk factors for CDI within 14 days of an initial
      negative test. We sought to determine the characteristics among hospitalized
      patients associated with risk of short-term acquisition of CDI. METHODS: A case
      control study was conducted. Cases were patients who converted from PCR negative
      to positive within 14 days. Each case was matched with three controls.
      Conditional logistic regression was used to estimate the association between
      patient characteristics and CDI. RESULTS: Of the 30 patients in our study who had
      a positive PCR within 14 days of a first negative PCR (cases), 15 (50%) occurred
      within 7 days of the initial test. Cases had a higher proportion of intravenous
      vancomycin use in the previous 8 weeks (odds ratio [OR], 3.38; 95% confidence
      interval [CI], 1.34-8.49) and were less likely to have recent antiviral agent use
      (OR, 0.30; 95% CI, 0.11-0.83) compared with controls. CONCLUSIONS: In
      hospitalized patients, treatment with intravenous vancomycin within the prior 8
      weeks of a first negative PCR test for C difficile is a risk factor for short
      term risk for hospital-acquired CDI. Repeat testing guidelines for C difficile
      PCR should take into consideration patients who may be at high risk for short
      term acquisition of CDI.

PMID- 25972334
TI  - Loss of BAP1 Expression in Basal Cell Carcinomas in Patients With Germline BAP1
      Mutations.
AB  - OBJECTIVES: Patients with heterozygous germline mutations in BRCA1-associated
      protein 1 (BAP1), a tumor suppressor gene, develop a tumor predisposition
      syndrome (OMIM 614327) with increased risk of uveal and cutaneous melanomas,
      cutaneous atypical and epithelioid melanocytic lesions, lung adenocarcinoma,
      clear cell renal cell carcinoma, and other tumors. Early recognition of this
      syndrome is of clinical importance. In addition, screening for BAP1 mutation,
      loss, and inactivation by performing BAP1 immunohistochemistry on cutaneous
      lesions would be a simple method for screening patients suspected of having
      germline BAP1 mutations. METHODS: We investigated BAP1 expression in seven basal
      cell carcinomas (BCCs) in two patients with germline BAP1 mutation and a family
      history of uveal melanoma. Six lesions were from the head and neck region and one
      from the shoulder. Thirty-one sporadic BCCs were included as controls. RESULTS:
      All seven BCCs in the patients with germline BAP1 mutations exhibited loss of
      BAP1 nuclear staining, while 30 (97%) of 31 sporadic BCCs exhibited positive BAP1
      nuclear staining. CONCLUSIONS: Loss of BAP1 expression could be associated with
      the development of BCC in patients with germline BAP1 mutations. These results
      suggest that BCC may be a component of the expanding category of tumors
      associated with this syndrome.

PMID- 25972336
TI  - Tattoos containing useful messages.

PMID- 25972337
TI  - What is hidden in tattoos?

PMID- 25972339
TI  - Correction.

PMID- 25972338
TI  - Test utilization is a quality control issue.

PMID- 25972340
TI  - High prevalence of elevated haemoglobin A1C among adolescent blood donors:
      Results from a voluntary screening programme including 31,546 adolescents.
AB  - More than 1 in 10 US adolescents have prediabetes or diabetes, and elevated
      glycosylated haemoglobin (HbA1C) in youth is associated with increased risk of
      death before the age of 55 years. We conducted a prospective, cross-sectional
      study of 31,546 consecutive volunteer blood donors, 16-19 years of age, who
      donated blood during school blood drives between 1 September 2011 and 21 December
      2012 in Texas. In the overall cohort, the prevalence of elevated HbA1C was 11.5%,
      including 11.0% in the prediabetes range (HbA1C 5.7%-6.4%) and 0.5% in the
      diabetes range (HbA1C ? 6.5%). The prevalence of elevated HbA1C was higher in
      boys compared with girls (15.7% vs. 7.9%, p < 0.001) and was especially high in
      racial/ethnic minorities (Blacks 32.7%, Asians 19.7%, Hispanics 13.1%) compared
      with Whites (8.0%, p < 0.001). There was a significant increase in total
      cholesterol and blood pressure across categories of increasing HbA1C in the
      overall cohort and stratified by sex and race/ethnicity. Blood donation
      programmes can serve as unique portals for health screening with potential for
      intervention in adolescents.

PMID- 25972341
TI  - The rate of aging: the rate of deficit accumulation does not change over the
      adult life span.
AB  - People age at different rates. We have proposed that rates of aging can be
      quantified by the rate at which individuals accumulate health deficits. Earlier
      estimates, using cross-sectional analyses suggested that deficits accumulated
      exponentially, at an annual rate of 3.5%. Here, we estimate the rate of deficit
      accumulation using longitudinal data from the Canadian National Population Health
      Survey. By analyzing age-specific trajectories of deficit accumulation in people
      aged 20 years and over (n = 13,668) followed biannually for 16 years, we found
      that the longitudinal average annual rate of deficit accumulation was 4.5% (+/
      0.75%). This estimate was notably stable during the adult life span. The
      corresponding average doubling time in the number of deficits was 15.4 (95% CI
      14.82-16.03) years, roughly 30% less than we had reported from the cross
      sectional analysis. Earlier work also established that the average number of
      deficits accumulated by individuals (N), equals the product of the intensity of
      environmental stresses (lambda) causing damage to the organism, by the average
      recovery time (W). At the individual level, changes in deficit accumulation can
      be attributed to both changes in environmental stresses and changes in recovery
      time. By contrast, at the population level, changes in the number of deficits are
      proportional to the changes in recovery time. In consequence, we propose here
      that the average recovery time, W doubles approximately every 15.4 years,
      independently of age. Such changes quantify the increase of vulnerability to
      stressors as people age that gives rise to increasing risk of frailty, disability
      and death. That deficit accumulation will, on average, double twice between ages
      50 and 80 highlights the importance of health in middle age on late life
      outcomes.

PMID- 25972342
TI  - Quantifying the Landscape for Development and Cancer from a Core Cancer Stem Cell
      Circuit.
AB  - Cancer presents a serious threat to human health. The understanding of the cell
      fate determination during development and tumor-genesis remains challenging in
      current cancer biology. It was suggested that cancer stem cell (CSC) may arise
      from normal stem cells or be transformed from normal differentiated cells. This
      gives hints on the connection between cancer and development. However, the
      molecular mechanisms of these cell-type transitions and the CSC formation remain
      elusive. We quantified landscape, dominant paths, and switching rates between
      cell types from a core gene regulatory network for cancer and development. Stem
      cell, CSC, cancer, and normal cell types emerge as basins of attraction on
      associated landscape. The dominant paths quantify the transition processes among
      CSC, stem cell, normal cell, and cancer cell attractors. Transition actions of
      the dominant paths are shown to be closely related to switching rates between
      cell types, but not always to the barriers in between, because of the presence of
      the curl flux. During the process of P53 gene activation, landscape topography
      changes gradually from a CSC attractor to a normal cell attractor. This confirms
      the roles of P53 of preventing the formation of CSC through suppressing self
      renewal and inducing differentiation. By global sensitivity analysis according to
      landscape topography and action, we identified key regulations determining cell
      type switchings and suggested testable predictions. From landscape view, the
      emergence of the CSCs and the associated switching to other cell types are the
      results of underlying interactions among cancer and developmental marker genes.
      This indicates that the cancer and development are intimately connected. This
      landscape and flux theoretical framework provides a quantitative way to
      understand the underlying mechanisms of CSC formation and interplay between
      cancer and development.

PMID- 25972344
TI  - Assembly and maintenance of the flagellum attachment zone filament in Trypanosoma
      brucei.
AB  - Adhesion of motile flagella to the cell body in Trypanosoma brucei requires a
      filamentous cytoskeletal structure termed the flagellum attachment zone (FAZ).
      Despite its essentiality, the complete molecular composition of the FAZ filament
      and its roles in FAZ filament assembly remain poorly understood. By localization
      based screening, we here identified a new FAZ protein, which we called FAZ2.
      Knockdown of FAZ2 disrupted the FAZ filament, destabilized multiple FAZ filament
      proteins and caused a cytokinesis defect. We also showed that FAZ2 depletion
      destabilized another new FAZ filament protein and several flagellum and
      cytoskeleton proteins. Furthermore, we identified CC2D and KMP11 as FAZ2 partners
      through affinity purification, and showed that they are each required for
      maintaining a stable complex. Finally, we demonstrated that FAZ filament proteins
      are incorporated into the FAZ filament from the proximal region, in contrast to
      the flagellum components, which are incorporated from the distal tip. In summary,
      we identified three new FAZ filament proteins and a FAZ filament protein complex,
      and our results suggest that assembly of the FAZ filament occurs at the proximal
      region and is essential to maintain the stability of FAZ filament proteins. 

PMID- 25972343
TI  - TET2 Mutations Affect Non-CpG Island DNA Methylation at Enhancers and
      Transcription Factor-Binding Sites in Chronic Myelomonocytic Leukemia.
AB  - TET2 enzymatically converts 5-methylcytosine to 5-hydroxymethylcytosine as well
      as other covalently modified cytosines and its mutations are common in myeloid
      leukemia. However, the exact mechanism and the extent to which TET2 mutations
      affect DNA methylation remain in question. Here, we report on DNA methylomes in
      TET2 wild-type (TET2-WT) and mutant (TET2-MT) cases of chronic myelomonocytic
      leukemia (CMML). We analyzed 85,134 CpG sites [28,114 sites in CpG islands (CGI)
      and 57,020 in non-CpG islands (NCGI)]. TET2 mutations do not explain genome-wide
      differences in DNA methylation in CMML, and we found few and inconsistent
      differences at CGIs between TET2-WT and TET2-MT cases. In contrast, we identified
      409 (0.71%) TET2-specific differentially methylated CpGs (tet2-DMCs) in NCGIs,
      86% of which were hypermethylated in TET2-MT cases, suggesting a strikingly
      different biology of the effects of TET2 mutations at CGIs and NCGIs. DNA
      methylation of tet2-DMCs at promoters and nonpromoters repressed gene expression.
      Tet2-DMCs showed significant enrichment at hematopoietic-specific enhancers
      marked by H3K4me1 and at binding sites for the transcription factor p300. Tet2
      DMCs showed significantly lower 5-hydroxymethylcytosine in TET2-MT cases. We
      conclude that leukemia-associated TET2 mutations affect DNA methylation at NCGI
      regions containing hematopoietic-specific enhancers and transcription factor
      binding sites.

PMID- 25972345
TI  - Cost-effectiveness analysis of parenteral antimicrobials for acute melioidosis in
      Thailand.
AB  - BACKGROUND: Melioidosis is a common community-acquired infectious disease in
      northeast Thailand associated with overall mortality of approximately 40% in
      hospitalized patients, and over 70% in severe cases. Ceftazidime is recommended
      for parenteral treatment in patients with suspected melioidosis. Meropenem is
      increasingly used but evidence to support this is lacking. METHODS: A decision
      tree was used to estimate the cost-effectiveness of treating non-severe and
      severe suspected acute melioidosis cases with either ceftazidime or meropenem.
      RESULTS: Empirical treatment with meropenem is likely to be cost-effective
      providing meropenem reduces mortality in severe cases by at least 9% and the
      proportion with subsequent culture-confirmed melioidosis is over 20%.
      CONCLUSIONS: In this context, treatment of severe cases with meropenem is likely
      to be cost-effective, while the evidence to support the use of meropenem in non
      severe suspected melioidosis is not yet available.

PMID- 25972347
TI  - Changes in HRQoL after 12 months of exercise linked to primary care are
      associated with fitness effects in older adults.
AB  - PURPOSE: To analyse the effects of 1 year of participation in a physical activity
      (PA) program linked to a health-care setting on physical fitness (PF) and health
      related quality of life (HRQoL) and to determine the relationships between PA, PF
      and HRQoL in middle-aged and older adults. METHODS: In total, 3214 participants
      were recruited from a health-care setting. Sociodemographic data, HRQoL
      questionnaires and PF tests were applied by 37 employees at baseline and 1 year
      later. The participants were placed in an exercise group (EG) (n = 2614) and the
      remaining participants (n = 600) were placed in the control group (CG). EG
      performed the program 3 days/week for 50-60 minutes per session involving brisk
      walking with intermittent flexibility, strength and balance
      activities/exercises.CG participants were asked to continue with their usual
      activities. Data analysis included repeated measures analysis of variance, linear
      regression and contingency analysis. RESULTS: EG showed significant mild-moderate
      improvement in all PF and HRQoL outcomes, especially in adjusted models. Changes
      in several PF variables were predictive of HRQoL changes. EG exhibited either
      improvements or no change in HRQoL dimensions. CG exhibited no change or declines
      in all dimensions. CONCLUSIONS: PF is positively related with HRQoL. PA
      significantly improved PF, especially the PF components more impaired at
      baseline.

PMID- 25972348
TI  - Problem drinking is rising among England's well educated women.

PMID- 25972349
TI  - Conversion disorder in a preschool age girl.
AB  - This article reports a case of a 5-year-old girl with clinical manifestations of
      a conversion disorder. Children presenting with a conversion disorder very often
      have multiple investigations and more than two-thirds of them are admitted to the
      hospital. This case illustrates the necessity of adapting, from the outset, a
      multidisciplinary approach to diagnosis and management, which helps in providing
      an explanatory model that takes into account stressors, factors within the child
      and the family, and aids in planning an appropriate psychotherapeutic
      intervention based on the child's and family's needs.

PMID- 25972346
TI  - Evolution of CONSTANS Regulation and Function after Gene Duplication Produced a
      Photoperiodic Flowering Switch in the Brassicaceae.
AB  - Environmental control of flowering allows plant reproduction to occur under
      optimal conditions and facilitates adaptation to different locations. At high
      latitude, flowering of many plants is controlled by seasonal changes in day
      length. The photoperiodic flowering pathway confers this response in the
      Brassicaceae, which colonized temperate latitudes after divergence from the
      Cleomaceae, their subtropical sister family. The CONSTANS (CO) transcription
      factor of Arabidopsis thaliana, a member of the Brassicaceae, is central to the
      photoperiodic flowering response and shows characteristic patterns of
      transcription required for day-length sensing. CO is believed to be widely
      conserved among flowering plants; however, we show that it arose after gene
      duplication at the root of the Brassicaceae followed by divergence of
      transcriptional regulation and protein function. CO has two close homologs,
      CONSTANS-LIKE1 (COL1) and COL2, which are related to CO by tandem duplication and
      whole-genome duplication, respectively. The single CO homolog present in the
      Cleomaceae shows transcriptional and functional features similar to those of COL1
      and COL2, suggesting that these were ancestral. We detect cis-regulatory and
      codon changes characteristic of CO and use transgenic assays to demonstrate their
      significance in the day-length-dependent activation of the CO target gene
      FLOWERING LOCUS T. Thus, the function of CO as a potent photoperiodic flowering
      switch evolved in the Brassicaceae after gene duplication. The origin of CO may
      have contributed to the range expansion of the Brassicaceae and suggests that in
      other families CO genes involved in photoperiodic flowering arose by convergent
      evolution. 

PMID- 25972350
TI  - Genitourinary tuberculosis, CA-125 and tuberculin anergy in disseminated
      tuberculosis.

PMID- 25972351
TI  - Running, ischaemic stroke and carotid artery dissection.

PMID- 25972352
TI  - Black oesophagus.

PMID- 25972353
TI  - The role of coagulation disorders in patients with retinal vein occlusion.
AB  - BACKGROUND: The role of a hypercoagulable state in the pathogenesis of retinal
      vein occlusion (RVO) has not been conclusively established. AIM: To analyse the
      prevalence of thrombophilia in RVO. DESIGN: Prospective case-control study.
      METHODS: All the patients diagnosed with RVO were referred to an Internal
      Medicine clinic and compared with sex- and age-matched individuals from a
      population-based cohort. Demographic, clinical and laboratory variables
      (including a thrombophilia panel) were analysed. RESULTS: One hundred and seventy
      patients (93 men and 77 women; 68 +/- 11 years) and 170 controls (80 men and 90
      women; 67 +/- 10 years) were included. RVO was peripheral in 113 cases. Genetic
      thrombophilia was detected in 13% of patients. Acquired thrombophilia was
      observed in 10% of cases and 4.7 % of controls (P < 0.01). Sixty-three percent of
      cases and 24.6% of controls had serum hyperhomocysteinemia (odds ratio [OR] 5.2,
      IC 95% 2.7-10.1; P < 0.0001) : In RVO patients aged <50 years (n = 11), 36.4% had
      genetic thrombophilia (P = 0.04), as well as 50% of those without vascular risk
      factors (n = 18; P = 0.01). Forty-one (24%) patients with RVO received
      antiplatelet agents and 13 (7.6%) were on anticoagulants due to preexistent
      atrial fibrillation. CONCLUSIONS: We suggest that, in patients with RVO,
      hyperhomocysteinemia and antiphospholipid syndrome should be ruled out. Moreover,
      a study of genetic thrombophilia should only be considered in those aged <50
      years or without cardiovascular risk factors. Antiplatelet therapy with aspirin
      is probably the treatment of choice of RVO, to reduce the overall vascular risk.
      Anticoagulation should only be considered in patients with high-risk
      thrombophilia.

PMID- 25972354
TI  - Modification of promoter spacer length in vaccinia virus as a strategy to control
      the antigen expression.
AB  - Vaccinia viruses (VACVs) with distinct early promoters have been developed to
      enhance antigen expression and improve antigen-specific CD8 T-cell responses. It
      has not been demonstrated how the length of the spacer between the coding region
      of the gene and its regulatory early promoter motif influences antigen
      expression, and whether the timing of gene expression can modify the antigen
      specific CD4 T-cell response. We generated several recombinant VACVs based on the
      attenuated modified vaccinia Ankara (MVA) strain, which express GFP or the
      Leishmania LACK antigen under the control of an optimized promoter, using
      different spacer lengths. Longer spacer length increased GFP and LACK early
      expression, which correlated with an enhanced LACK-specific memory CD4 and CD8 T
      cell response. These results show the importance of promoter spacer length for
      early antigen expression by VACV and provide alternative strategies for the
      design of poxvirus-based vaccines. 

PMID- 25972355
TI  - Increased endothelial cell permeability in endoglin-deficient cells.
AB  - Endoglin (ENG) is a TGF-beta superfamily coreceptor essential for vascular
      endothelium integrity. ENG mutations lead to a vascular dysplasia associated with
      frequent hemorrhages in multiple organs, whereas ENG null mouse embryos die at
      midgestation with impaired heart development and leaky vasculature. ENG interacts
      with several proteins involved in cell adhesion, and we postulated that it
      regulates vascular permeability. The current study assessed the permeability of
      ENG homozygous null (Eng(-/-)), heterozygous (Eng(+/-)), and normal (Eng(+/+))
      mouse embryonic endothelial cell (EC) lines. Permeability, measured by passage of
      fluorescent dextran through EC monolayers, was increased 2.9- and 1.7-fold for
      Eng(-/-) and Eng(+/-) ECs, respectively, compared to control ECs and was not
      increased by TGF-beta1 or VEGF. Prolonged starvation increased Eng(-/-) EC
      permeability by 3.7-fold with no effect on control ECs; neutrophils transmigrated
      faster through Eng(-/-) than Eng(+/+) monolayers. Using a pull-down assay, we
      demonstrate that Ras homolog gene family (Rho) A is constitutively active in Eng(
      /-) and Eng(+/-) ECs. We show that the endothelial barrier destabilizing factor
      thrombospondin-1 and its receptor-like protein tyrosine phosphatase are
      increased, whereas stabilizing factors VEGF receptor 2, vascular endothelial
      cadherin, p21-activated kinase, and Ras-related C3 botulinum toxin substrate 2
      are decreased in Eng(-/-) cells. Our findings indicate that ENG deficiency leads
      to EC hyperpermeability through constitutive activation of RhoA and
      destabilization of endothelial barrier function.

PMID- 25972357
TI  - Tobacco industry lobbying undermines public health in Asia.

PMID- 25972358
TI  - The molecular basis of the non-thyroidal illness syndrome.
AB  - The 'sick euthyroid syndrome' or 'non-thyroidal illness syndrome' (NTIS) occurs
      in a large proportion of hospitalized patients and comprises a variety of
      alterations in the hypothalamus-pituitary-thyroid (HPT) axis that are observed
      during illness. One of the hallmarks of NTIS is decreased thyroid hormone (TH)
      serum concentrations, often viewed as an adaptive mechanism to save energy.
      Downregulation of hypophysiotropic TRH neurons in the paraventricular nucleus of
      the hypothalamus and of TSH production in the pituitary gland points to disturbed
      negative feedback regulation during illness. In addition to these alterations in
      the central component of the HPT axis, changes in TH metabolism occur in a
      variety of TH target tissues during NTIS, dependent on the timing, nature and
      severity of the illness. Cytokines, released during illness, are known to affect
      a variety of genes involved in TH metabolism and are therefore considered a major
      determinant of NTIS. The availability of in vivo and in vitro models for NTIS has
      elucidated part of the mechanisms involved in the sometimes paradoxical changes
      in the HPT axis and TH responsive tissues. However, the pathogenesis of NTIS is
      still incompletely understood. This review focusses on the molecular mechanisms
      involved in the tissue changes in TH metabolism and discusses the gaps that still
      require further research. 

PMID- 25972359
TI  - Long-term oral exposure to bisphenol A induces glucose intolerance and insulin
      resistance.
AB  - Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic
      results have suggested an association between exposure to BPA and cardiovascular
      disease, type 2 diabetes, and obesity. We investigated the in vivo effects of
      long-term oral exposure to BPA on insulin resistance and glucose intolerance. In
      the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were
      treated with 50 MUg/kg body weight per day of BPA orally for 12 weeks. Long-term
      oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance
      in growing male mice. Intraperitoneal glucose tolerance tests showed that the
      mice that received an HFD and BPA exhibited a significantly larger area under the
      curve than did those that received an HFD only (119.9+/-16.8 vs. 97.9+/-18.2
      mM/min, P=0.027). Body weight, percentage of white adipose tissue, and percentage
      of body fat did not differ between the two groups of mice. However, treatment
      with BPA reduced Akt phosphorylation at position Thr308 and GSK3beta
      phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum
      adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor
      alpha, although these findings were not statistically significant. Treatment with
      BPA did not induce any detrimental changes in the islet area or morphology or the
      insulin content of beta cells. In conclusion, long-term oral exposure to BPA
      induced glucose intolerance and insulin resistance in growing mice. Decreased Akt
      phosphorylation in skeletal muscle by way of altered serum adipocytokine levels
      might be one mechanism by which BPA induces glucose intolerance.

PMID- 25972360
TI  - Why we need to move beyond diagnosis-related groups and how we might do so.
AB  - Diagnosis-related groups are widespread across Europe and they are meant to be a
      central instrument to improve the activity and efficiency of hospitals. However,
      there are many examples of diagnosis-related groups having adverse effects which
      are difficult to control and which endanger the goals of health care systems in
      terms of efficiency, equity and quality. Political and administrative decision
      makers therefore need to fundamentally rethink hospital governance and consider
      new systems of budgeting and performance measurement. Central Denmark Region is
      currently piloting a system, based on the Triple Aim approach, which may offer
      inspiration. 

PMID- 25972356
TI  - Deubiquitinases in cancer.
AB  - Deubiquitinases are deubiquitinating enzymes (DUBs), which remove ubiquitin from
      proteins, thus regulating their proteasomal degradation, localization and
      activity. Here, we discuss DUBs as anti-cancer drug targets. 

PMID- 25972361
TI  - Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in
      high-grade serous ovarian cancer.
AB  - Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of
      COX expression and function have been unclear and controversial. In this report,
      patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data
      through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA
      expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX
      1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1
      in HGSOC tumors was confirmed in an independent tissue microarray. In contrast,
      lower or similar expression of COX-1 compared to COX-2 was observed in
      endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC
      representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple
      pro-tumorigenic pathways. Functional cell viability, clonogenicity, and
      migration/invasion assays were consistent with transcriptomic changes. These
      effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our
      results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors
      and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian
      cancer cells. These findings provide additional insight into the role of COX-1 in
      human ovarian cancer and support further development of methods to selectively
      target COX-1 in the management of HGSOC tumors. 

PMID- 25972362
TI  - A novel oHSV-1 targeting telomerase reverse transcriptase-positive cancer cells
      via tumor-specific promoters regulating the expression of ICP4.
AB  - Virotherapy is a promising strategy for cancer treatment. Using the human
      telomerase reverse transcriptase promoter, we developed a novel tumor-selective
      replication oncolytic HSV-1. Here we showed that oHSV1-hTERT virus was cytopathic
      in telomerase-positive cancer cell lines but not in telomerase-negative cell
      lines. In intra-venous injection in mice, oHSV1-hTERT was safer than its parental
      oHSV1-17+. In human blood cell transduction assays, both viruses transduced few
      blood cells and the transduction rate for oHSV1-hTERT was even less than that for
      its parental virus. In vivo, oHSV1-hTERT inhibited growth of tumors and prolong
      survival in telomerase-positive xenograft tumor models. Therefore, we concluded
      that this virus may be a safe and effective therapeutic agent for cancer
      treatment, warranting clinical trials in humans.

PMID- 25972363
TI  - DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer
      effect of 2-methoxyestradiol.
AB  - 2-Methoxyestradiol (2-ME) is a physiological metabolite of 17beta-estradiol. At
      pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in
      tumor models. Here we investigated the effect of physiologically relevant
      concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME
      increased nuclear localization of neuronal nitric oxide synthase, resulting in
      nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis
      in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with
      potential anti-cancer properties. 

PMID- 25972365
TI  - Toe walking as a presenting sign of systemic lupus erythematosus.
AB  - Toe walking is a previously unreported presentation of systemic lupus
      erythematosus (SLE). We describe a patient who presented with profound
      multisystem involvement that was preceded by one month of toe walking and
      multiple flexion contractures without arthritis. Her lupus is now under control
      after aggressive therapy, yet she continues to struggle with tendinopathy despite
      continued physical and occupational therapy. Lupus should be considered in the
      appropriate clinical context in children who have new-onset contractures due to
      tight tendons. 

PMID- 25972366
TI  - Electroconvulsive therapy as a treatment for refractory neuropsychiatric lupus
      with catatonia: three case studies and literature review.
AB  - Neuropsychiatric disorders associated with systemic lupus erythematosus are very
      common. Treatment generally consists of glucocorticoids and immunosuppressive
      therapy; however, some cases are unresponsive. Electroconvulsive therapy (ECT) is
      a recognized treatment modality in psychiatry and is an option for refractory
      cases of neuropsychiatric lupus. This report describes three cases of
      neuropsychiatric lupus that improved with ECT after failure of antipsychotics and
      immunosuppressive therapy. All cases met DSM-5 criteria for catatonia (case 1:
      agitation, stereotypies, and grimacing; case 2: stupor, mutism, and grimacing;
      case 3: agitation, mutism, and stereotypies); therefore, ECT was indicated. This
      case series shows that ECT can be a therapeutic option in patients with
      neuropsychiatric lupus, especially when associated with catatonia and
      unresponsive to conventional treatment. 

PMID- 25972364
TI  - Chinese SLE Treatment and Research group (CSTAR) registry: V. gender impact on
      Chinese patients with systemic lupus erythematosus.
AB  - INTRODUCTION: Many studies have shown that differences were observed between male
      and female lupus patients. Although systemic lupus erythematosus (SLE) affects
      mostly females (female:male ratio 9:1), male SLE patients show higher mortality
      due to kidney and neurological disease. Currently there are limited
      epidemiological data concerning lupus in the Chinese population. As such, the
      Chinese SLE Treatment and Research group (CSTAR) developed the first online
      registry of Chinese lupus patients in 2009, and represents a multicenter
      observational study that attempts to describe and compile the major clinical
      characteristics of lupus in Chinese patients. OBJECTIVE: To investigate the
      effect of gender on the phenotypes of Chinese SLE patients. PATIENTS AND METHODS:
      Data for 2104 SLE patients were prospectively collected and included in the CSTAR
      registry. Patients fulfilled the 1997 American College of Rheumatology (ACR) SLE
      classification criteria. We conducted a cross-sectional case-control study to
      analyze patient clinical and laboratory data at onset and at enrollment. SLE
      disease activity scores (SLEDAI) were also measured at enrollment. RESULTS: This
      study included 1914 women and 190 men. Males and females showed no differences in
      mean ages at onset, delay of diagnosis and disease duration. Males presented more
      frequently with fever (p = 0.003), while musculoskeletal involvement (p = 0.001)
      and cytopenia (p = 0.017) was more common in females as the initial manifestation
      at onset of SLE. For manifestations at enrollment, males presented more
      frequently with fever (p = 0.005), renal disease (p = 0.019), vasculitis (p =
      0.032) and neuropsychiatric lupus (p = 0.007). For cumulative manifestations at
      enrollment, males presented more frequently with discoid rash (p < 0.001) and
      neuropsychiatric lupus (p = 0.036), while less frequently with arthritis (p =
      0.011). However, the laboratory data showed no significant differences between
      the two groups at enrollment. Males also had higher SLEDAI scores at enrollment
      (p = 0.002). CONCLUSIONS: Renal disease, vasculitis and neuropsychiatric lupus
      are more common in male SLE patients with higher SLEDAI scores compared to female
      SLE patients in China.

PMID- 25972368
TI  - 128-slice dual-source CT coronary angiography with prospectively
      electrocardiography-triggered high-pitch spiral mode: radiation dose, image
      quality, and diagnostic acceptability.
AB  - BACKGROUND: Dual-source computed tomography (CT) enables CT coronary angiography
      (CTCA) with a prospectively electrocardiography (ECG)-triggered high-pitch spiral
      (HPS) mode. PURPOSE: To evaluate the radiation dose, image quality, and
      diagnostic acceptability of the HPS mode in CTCA and to compare HPS with the step
      and-shoot (SAS) and low-pitch spiral (LPS) modes. MATERIAL AND METHODS: One
      hundred and thirty-eight patients who underwent CTCA with a 128-slice dual-source
      CT scanner were retrospectively included in this study. Seventeen patients
      (average heart rate of <=65 beats per minute [bpm] prior to acquisition) were
      evaluated in the HPS mode, 88 (average heart rate of >65 and <=80 bpm prior to
      acquisition) in the SAS mode, and 33 (average heart rate of >80 bpm prior to
      acquisition or patients with an unstable heart rhythm) in the LPS mode. Radiation
      dose and image noise were recorded for each patient. Diagnostic acceptability was
      graded using a four-point scale (1, unacceptable; 2, suboptimal; 3, acceptable;
      4, fully acceptable). RESULTS: The effective dose in the HPS mode was 1.5 +/- 0.2
      mSv, which was lower than that in SAS (8.9 +/- 2.7 mSv) and LPS (21.5 +/- 4.3
      mSv) modes. There were no significant differences in the image noise levels in
      the descending aorta and left atrium. The average per-patient diagnostic
      acceptability was 3.2, 3.6, and 3.7 in HPS, SAS, and LPS modes, respectively.
      CONCLUSION: The radiation dose is lower with HPS than with other modes, and the
      HPS mode-acquired images of patients with heart rates of <=65 bpm are nearly
      acceptable for diagnostic image interpretation.

PMID- 25972367
TI  - Specific systemic lupus erythematosus disease manifestations in the six months
      prior to conception are associated with similar disease manifestations during
      pregnancy.
AB  - Past studies have focused on aggregate lupus disease activity during pregnancy
      and have produced conflicting results. Our study evaluated lupus activity based
      on involvement of five specific organ systems during the six months prior to
      conception and during pregnancy. We assessed 147 pregnancies among 113 women
      followed at Brigham and Women's Lupus Center, 1990-2013. Organ-specific activity
      included hematologic disorder, nephritis, skin disease, arthritis, and serositis.
      We hypothesized that the presence of organ-specific activity six months prior to
      conception would increase the risk for that same type of activity during
      pregnancy. Our study population was 68% white; 100% had a positive ANA and 30%
      had a history of nephritis. Among women with organ-specific lupus activity during
      the six months before conception, the crude odds for the same type of activity
      during pregnancy was 7.7- to 32.5-fold higher compared to women without that type
      of activity immediately before conception. An adjusted logistic regression model
      also indicated significantly higher odds of organ-specific activity during
      pregnancy if that type of activity were present six months before conception.
      Approaching lupus based on specific organ systems may be a useful way for women
      and their physicians to consider the potential risk for disease activity during
      pregnancy. 

PMID- 25972370
TI  - Use of diffusion-weighted magnetic resonance imaging to distinguish between lung
      cancer and focal inflammatory lesions: a comparison of intravoxel incoherent
      motion derived parameters and apparent diffusion coefficient.
AB  - Background Using imaging techniques to diagnose malignant and inflammatory
      lesions in the lung can be challenging. Purpose To compare intravoxel incoherent
      motion (IVIM) and apparent diffusion coefficient (ADC) magnetic resonance imaging
      (MRI) analysis in their ability to discriminate lung cancer from focal
      inflammatory lung lesions. Material and Methods Thirty-eight patients with lung
      masses were included: 30 lung cancers and eight inflammatory lesions. Patients
      were imaged with 3.0T MRI diffusion weighted imaging (DWI) using 10 b values
      (range, 0-1000 s/mm2). Tissue diffusivity ( D), pseudo-diffusion coefficient (
      D*), and perfusion fraction ( f) were calculated using segmented biexponential
      analysis. ADC (total) was calculated with monoexponential fitting of the DWI
      data. D, D*, f, and ADC were compared between lung cancer and inflammatory lung
      lesions. Receiver operating characteristic analysis was performed for all DWI
      parameters. Results The ADC was significantly higher for inflammatory lesions
      than for lung cancer ([1.21 +/- 0.20] * 10-3 mm2/s vs. [0.97 +/- 0.15] * 10-3
      mm2/s; P = 0.004). By IVIM, f was found to be significantly higher in
      inflammatory lesions than lung cancer ([46.10 +/- 12.92] % vs. [29.29 +/- 10.89]
      %; P = 0.005). There was no difference in D and D* between lung cancer and
      inflammatory lesions ( P = 0.747 and 0.124, respectively). f showed comparable
      diagnostic performance with ADC in differentiating lung cancer from inflammatory
      lung lesions, with areas under the curve of 0.833 and 0.826, sensitivity 80.0%
      and 73.3%, and specificity 75.0% and 87.5%, respectively. Conclusion The IVIM
      parameter f value provides comparable diagnostic performance with ADC and could
      be used as a surrogate marker for differentiating lung cancer from inflammatory
      lesions.

PMID- 25972369
TI  - Comparative study of CT appearances in renal oncocytoma and chromophobe renal
      cell carcinoma.
AB  - BACKGROUND: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC)
      share histologic and some imaging features. PURPOSE: To investigate the
      multidetector computed tomography (MDCT) characteristics of these two tumor
      types. MATERIAL AND METHODS: Fifty-six patients with RO and 54 patients with
      ChRCC were studied retrospectively. MDCT was undertaken to investigate
      differences in tumor characteristics. RESULTS: Calcifications were visible in 24
      (42.8%) patients with RO and in 11 (20.4%) patients with ChRCC (P = 0.011). 26
      patients with RO had stellate scars as did 14 patients with ChRCC (P = 0.025).
      Spoken-wheel-like enhancement was visible in 41 patients with RO and in 11 with
      ChRCC (P < 0.001). Thirty-nine (69.6%) patients with RO and nine (16.7%) patients
      with ChRCC showed segmental inversion (P < 0.001). Two patients with RO had
      retroperitoneal lymph node enlargement as did 13 patients with ChRCC (P = 0.002).
      Combined evaluation of stellate scar, spoken-wheel-like enhancement, and
      segmental enhancement inversion features were found to have a sensitivity of
      99.1% (106 of 107), a specificity of 100% (3 of 3), a positive predictive value
      of 100% (106 of 106), and a negative predictive value of 75% (3 of 4). The
      attenuation of RO tumors was greater than that of ChRCC tumors, normal renal
      parenchyma on unenhanced CT (P = 0.031). Enhancement was higher with RO than with
      ChRCC tumors in all phases (P = 0.021, < 0.001, and 0.007, respectively).
      CONCLUSION: CT imaging features such as stellate scar, spoken-wheel-like
      enhancement, and segmental enhancement inversion were more common in RO and they
      may help in differentiating RO from ChRCC.

PMID- 25972371
TI  - Imaging of biliary complications in recipients of right-lobe living donor liver
      transplantation.
AB  - Right-lobe living donor liver transplantation (RL-LDLT) is a common method
      devised in order to fulfill the demands of donor organ shortage in adult patients
      with end-stage liver diseases. However, biliary complications remain as the
      "Achilles' heel" of RL-LDLT, with wide variety of incidence among transplantation
      centers. Patients with biliary complications after RL-LDLT may have similar
      clinical presentations to those with other causes of graft dysfunction.
      Therefore, radiological evaluation plays a key role for differential diagnosis of
      such complications. In this article, we discuss the various methods of biliary
      reconstruction and imaging findings of common and uncommon biliary complications
      in recipients of RL-LDLT.

PMID- 25972372
TI  - Safety of psychotropic drugs in pregnancy.

PMID- 25972374
TI  - TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through
      p62/SQSTM1 phosphorylation.
AB  - Selective autophagy adaptor proteins, including p62/SQSTM1, play pivotal roles in
      the targeted degradation of ubiquitinated proteins or organelles through the
      autophagy-lysosome system. However, how autophagy adaptors promote the
      autophagosomal engulfment of selected substrates is poorly understood. Here, we
      show that p62 phosphorylation at S403 is required for the efficient
      autophagosomal engulfment of polyubiquitinated mitochondria during Parkin
      dependent mitophagy. p62 is able to interact with Parkin-recruited mitochondria
      without S403 phosphorylation under mitophagy-inducing conditions, but those
      mitochondria are not enclosed by autophagosomes. Intriguingly, the S403
      phosphorylation occurs only in the early period of mitochondrial depolarization.
      Optineurin and TANK-binding kinase 1 (TBK1) are transiently recruited to the
      polyubiquitinated mitochondria, and the activated TBK1 phosphorylates p62 at
      S403. TBK1 inhibitor, BX795, prevents the p62-mediated autophagosomal engulfment
      of Parkin-recruited mitochondria. Our results suggest that TBK1-mediated S403
      phosphorylation regulates the efficient autophagosomal engulfment of
      ubiquitinated mitochondria as an immediate response to the mitochondrial
      depolarization. 

PMID- 25972373
TI  - Evaluating the Hispanic Paradox in the Context of Adolescent Risky Sexual
      Behavior: The Role of Parent Monitoring.
AB  - OBJECTIVE: In the United States, Hispanic adolescents are at elevated risk for
      negative outcomes related to risky sexual behavior. To evaluate potential
      protective factors for this group, we examined the fit of the Hispanic Paradox
      for sexual behavior among high-risk youth and the moderating role of parent
      monitoring. METHOD: We enrolled 323 justice-involved Hispanic youth (73% male;
      mean age 16 years), and measured generational status, parent monitoring
      (monitoring location, who children spend time with outside of school, family
      dinner frequency), and sexual risk behavior. RESULTS: There were no main effects
      for generational status on sexual behavior. Parent monitoring of location
      moderated the relationship between generational status and sexual behavior, such
      that greater monitoring of location was associated with less risky sexual
      behavior, but only for youth second generation and above. CONCLUSIONS: Rather
      than direct evidence supporting the Hispanic Paradox, we found a more nuanced
      relationship for generational status in this sample.

PMID- 25972375
TI  - Dominant, toxic gain-of-function mutations in gars lead to non-cell autonomous
      neuropathology.
AB  - Charcot-Marie-Tooth (CMT) neuropathies are collectively the most common
      hereditary neurological condition and a major health burden for society. Dominant
      mutations in the gene GARS, encoding the ubiquitous enzyme, glycyl-tRNA
      synthetase (GlyRS), cause peripheral nerve degeneration and lead to CMT disease
      type 2D. This genetic disorder exemplifies a recurring motif in
      neurodegeneration, whereby mutations in essential, widely expressed genes have
      selective deleterious consequences for the nervous system. Here, using novel
      Drosophila models, we show a potential solution to this phenomenon. Ubiquitous
      expression of mutant GlyRS leads to motor deficits, progressive neuromuscular
      junction (NMJ) denervation and pre-synaptic build-up of mutant GlyRS.
      Intriguingly, neuronal toxicity is, at least in part, non-cell autonomous, as
      expression of mutant GlyRS in mesoderm or muscle alone results in similar
      pathology. This mutant GlyRS toxic gain-of-function, which is WHEP domain
      dependent, coincides with abnormal NMJ assembly, leading to synaptic
      degeneration, and, ultimately, reduced viability. Our findings suggest that
      mutant GlyRS gains access to ectopic sub-compartments of the motor neuron,
      providing a possible explanation for the selective neuropathology caused by
      mutations in a widely expressed gene. 

PMID- 25972376
TI  - Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical
      roles in craniofacial, heart and brain development.
AB  - Kabuki syndrome (KS) is a rare multiple congenital anomaly syndrome characterized
      by distinctive facial features, global developmental delay, intellectual
      disability and cardiovascular and musculoskeletal abnormalities. While mutations
      in KMT2D have been identified in a majority of KS patients, a few patients have
      mutations in KDM6A. We analyzed 40 individuals clinically diagnosed with KS for
      mutations in KMT2D and KDM6A. Mutations were detected in KMT2D in 12 and KDM6A in
      4 cases, respectively. Observed mutations included single-nucleotide variations
      and indels leading to frame shifts, nonsense, missense or splice-site
      alterations. In two cases, we discovered overlapping chromosome X microdeletions
      containing KDM6A. To further elucidate the functional roles of KMT2D and KDM6A,
      we knocked down the expression of their orthologs in zebrafish. Following
      knockdown of kmt2d and the two zebrafish paralogs kdm6a and kdm6al, we analyzed
      morphants for developmental abnormalities in tissues that are affected in
      individuals with KS, including craniofacial structures, heart and brain. The
      kmt2d morphants exhibited severe abnormalities in all tissues examined. Although
      the kdm6a and kdm6al morphants had similar brain abnormalities, kdm6a morphants
      exhibited craniofacial phenotypes, whereas kdm6al morphants had prominent defects
      in heart development. Our results provide further support for the similar roles
      of KMT2D and KDM6A in the etiology of KS by using a vertebrate model organism to
      provide direct evidence of their roles in the development of organs and tissues
      affected in KS patients. 

PMID- 25972377
TI  - Mouse model of human RPE65 P25L hypomorph resembles wild type under normal light
      rearing but is fully resistant to acute light damage.
AB  - Human RPE65 mutations cause a spectrum of blinding retinal dystrophies from
      severe early-onset disease to milder manifestations. The RPE65 P25L missense
      mutation, though having <10% of wild-type (WT) activity, causes relatively mild
      retinal degeneration. To better understand these mild forms of RPE65-related
      retinal degeneration, and their effect on cone photoreceptor survival, we
      generated an Rpe65/P25L knock-in (KI/KI) mouse model. We found that, when subject
      to the low-light regime (~100 lux) of regular mouse housing, homozygous
      Rpe65/P25L KI/KI mice are morphologically and functionally very similar to WT
      siblings. While mutant protein expression is decreased by over 80%, KI/KI mice
      retinae retain comparable 11-cis-retinal levels with WT. Consistently, the
      scotopic and photopic electroretinographic (ERG) responses to single-flash
      stimuli also show no difference between KI/KI and WT mice. However, the recovery
      of a-wave response following moderate visual pigment bleach is delayed in KI/KI
      mice. Importantly, KI/KI mice show significantly increased resistance to high
      intensity (20 000 lux for 30 min) light-induced retinal damage (LIRD) as compared
      with WT, indicating impaired rhodopsin regeneration in KI/KI. Taken together, the
      Rpe65/P25L mutant produces sufficient chromophore under normal conditions to keep
      opsins replete and thus manifests a minimal phenotype. Only when exposed to
      intensive light is this hypomorphic mutation manifested physiologically, as its
      reduced expression and catalytic activity protects against the successive cycles
      of opsin regeneration underlying LIRD. These data also help define minimal
      requirements of chromophore for photoreceptor survival in vivo and may be useful
      in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans. 

PMID- 25972379
TI  - Beneficial Effect of Flavone Derivatives on Abeta-Induced Memory Deficit Is
      Mediated by Peroxisome Proliferator-Activated Receptor gamma Coactivator 1alpha:
      A Comparative Study.
AB  - In the present study, the neuroprotective effect of 5-hydroxy-6,7,4'
      trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison
      with another flavone, 5,7,4'-trihydroxyflavone (flavone 2) on the hippocampus of
      amyloid beta (Abeta)-injected rats. Rats were treated with the 2 flavones (1
      mg/kg/d) for 1 week before Abeta injection. Seven days after Abeta
      administration, memory function of rats was assessed in a passive avoidance test
      (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM),
      peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC
      1alpha), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK),
      AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear
      respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis.
      Our results showed an improvement in memory in rats pretreated with flavonoids.
      At the molecular level, phosphorylation of CREB, known as the master modulator of
      memory processes, increased. On the other hand, the level of mitochondrial
      biogenesis factors, PGC-1alpha and its downstream molecules NRF-1 and TFAM
      significantly increased by dietary administration of 2 flavones. In addition,
      flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial
      membrane potential reduction. Our results provided evidence that flavone 1 is
      more effective than flavone 2 presumably due to its O-methylated groups. In
      conclusion, it seems that in addition to classical antioxidant effect, flavones
      exert part of their protective effects through mitochondrial biogenesis. 

PMID- 25972380
TI  - Echocardiographic images of organised pericardial thrombus in type A aortic
      dissection.

PMID- 25972381
TI  - An unusual presentation of cardiac tamponade associated with Epstein-Barr virus
      infection.
AB  - We present a case of an 80-year-old woman who presented with a dry cough,
      shortness of breath and general malaise. She had presented 5 days previously with
      a sore throat, feeling feverish and with non-specific symptoms. Her background
      included paroxysmal atrial fibrillation and hypertension. She was initially
      thought to have decompensated heart failure secondary to atrial fibrillation and
      was initiated on diuretic therapy. However, a transthoracic echocardiogram
      performed revealed collapse of the right ventricle and a swinging heart,
      suggestive of cardiac tamponade. The patient underwent therapeutic
      pericardiocentesis where 700 mL of exudative, blood-stained fluid was drained.
      Subsequent testing of the pericardial fluid revealed the presence of Epstein-Barr
      virus DNA. Serial follow-up transthoracic echocardiograms revealed resolution of
      the pericardial effusion and the patient remained asymptomatic. 

PMID- 25972382
TI  - Acute STEMI in the setting of a single coronary artery anomaly.
AB  - We report a case of a patient admitted with an acute ST elevation myocardial
      infarction following occlusion of his right coronary artery, successfully treated
      with thrombectomy and percutaneous coronary intervention (PCI). Coronary
      angiography and multislice CT revealed a single right coronary artery with two
      anomalous branches (constituting the left coronary system); one branch passed
      between the pulmonary trunk and the aorta before dividing into three separate
      branches, while the other anomalous branch passed anterior to the pulmonary
      trunk, consistent with a Yamanaka R-IIIC classification. The course of this
      Yamanaka R-IIIC subtype is unusual as both anomalous branches combine to form a
      dual origin left anterior descending artery. The course of these anomalous
      branches places the patient at an increased risk of future myocardial ischaemia,
      infarction and sudden cardiac death. As symptoms typically develop on exertion,
      this cohort may benefit from exercise myocardial perfusion imaging to identify
      high-risk patients. 

PMID- 25972383
TI  - Task-Shifting From Physicians to Nurses in Primary Care and its Impact on
      Resource Utilization: A Systematic Review and Meta-Analysis of Randomized
      Controlled Trials.
AB  - Task-shifting from physicians to nurses has gained increasing interest in health
      policy but little is known about its efficiency. This systematic review was
      conducted to compare resource utilization with task-shifting from physicians to
      nurses in primary care. Literature searches yielded 4,589 citations. Twenty
      studies comprising 13,171 participants met the inclusion criteria. Meta-analyses
      showed nurses had more return consultations and longer consultations than
      physicians but were similar in their use of referrals, prescriptions, or
      investigations. The evidence has limitations, but suggests that the effects may
      be influenced by the utilization of resources, context of care, available
      guidance, and supervision. Cost data suggest physician-nurse salary and
      physician's time spent on supervision and delegation are important components of
      nurse-led care costs. More rigorous research involving a wider range of nurses
      from many countries is needed reporting detailed accounts of nurses' roles and
      competencies, qualifications, training, resources, time available for
      consultations, and all-cause costs. 

PMID- 25972384
TI  - Language Barriers to Defining Concepts in Medicine: The Case of Palliative
      Sedation.

PMID- 25972385
TI  - Doctors in New York "pill mill" worked under daily threats, court hears.

PMID- 25972386
TI  - Enforcement of science-using a Clostridium perfringens outbreak investigation to
      take legal action.
AB  - BACKGROUND: We report an outbreak of Clostridium perfringens in a care home in
      North East England. METHODS: A retrospective cohort study was used to investigate
      this outbreak. Faecal samples were obtained from symptomatic residents.
      Environmental Health Officers carried out a food hygiene inspection and formal
      statements were taken. RESULTS: Fifteen residents reported illness and the
      epidemic curve was suggestive of a point source outbreak. Results suggest that
      illness was associated with consumption of mince & vegetable pie and/or gravy.
      There were a number of issues with food served, in particular the mince products
      had been cooked, cooled, reheated and served again over a period of several days.
      Faecal sampling revealed the presence of C.perfringens enterotoxin gene and four
      samples were indistinguishable by fluorescent amplified fragment length
      polymorphism, indicating a likely common source. The operator of the home was
      charged with three offences under the General Food Regulations 2004 and the Food
      Hygiene (England) Regulations 2006 and was convicted on all counts. CONCLUSIONS:
      An outbreak of C.perfringens occurred in a care home. The likely cause was
      consumption of mince & vegetable pie and/or gravy. Epidemiological evidence can
      be used to help prosecute businesses with food safety offences in such
      circumstances.

PMID- 25972378
TI  - Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and
      PPP2R5D cause human overgrowth.
AB  - Overgrowth syndromes comprise a group of heterogeneous disorders characterised by
      excessive growth parameters, often in association with intellectual disability.
      To identify new causes of human overgrowth, we have been undertaking trio-based
      exome sequencing studies in overgrowth patients and their unaffected parents.
      Prioritisation of functionally relevant genes with multiple unique de novo
      mutations revealed four mutations in protein phosphatase 2A (PP2A) regulatory
      subunit B family genes protein phosphatase 2, regulatory Subunit B', beta
      (PPP2R5B); protein phosphatase 2, regulatory Subunit B', gamma (PPP2R5C); and
      protein phosphatase 2, regulatory Subunit B', delta (PPP2R5D). This observation
      in 3 related genes in 111 individuals with a similar phenotype is greatly in
      excess of the expected number, as determined from gene-specific de novo mutation
      rates (P = 1.43 * 10(-10)). Analysis of exome-sequencing data from a follow-up
      series of overgrowth probands identified a further pathogenic mutation, bringing
      the total number of affected individuals to 5. Heterozygotes shared similar
      phenotypic features including increased height, increased head circumference and
      intellectual disability. The mutations clustered within a region of nine amino
      acid residues in the aligned protein sequences (P = 1.6 * 10(-5)). We mapped the
      mutations onto the crystal structure of the PP2A holoenzyme complex to predict
      their molecular and functional consequences. These studies suggest that the
      mutations may affect substrate binding, thus perturbing the ability of PP2A to
      dephosphorylate particular protein substrates. PP2A is a major negative regulator
      of v-akt murine thymoma viral oncogene homolog 1 (AKT). Thus, our data further
      expand the list of genes encoding components of the phosphatidylinositol-4,5
      bisphosphate 3-kinase (PI3K)/AKT signalling cascade that are disrupted in human
      overgrowth conditions. 

PMID- 25972387
TI  - Using a covered stent for large cerebral aneurysms treated with stent-assisted
      coiling.
AB  - PURPOSE: The purpose of this article is to evaluate the efficacy and safety of
      covered stent implantation for large intracranial aneurysms treated with stent
      assisted coiling. MATERIALS AND METHODS: Seven patients with a cerebral aneurysm
      were selected for this study. The aneurysms were located at the cavernous segment
      of the internal carotid artery in three cases, the supraclinoid segment in two
      and the vertebrobasilar junction in one. Aneurysm diameter was 10-25 mm. Mass
      effect symptoms occurred in six patients, epistaxis in one and subarachnoid
      hemorrhage in one. All patients underwent endovascular reconstruction with stent
      assisted coiling and a covered stent. Five had undergone conventional
      endovascular embolization with stent-assisted coiling three to six months
      previously; the covered stent was then navigated through the existing stent and
      deployed to cover the aneurysm neck. In two cases, the covered stent was deployed
      after stent-assisted coiling in a single procedure. RESULTS: Angiography showed
      that all aneurysms were excluded from the circulation and parent arteries were
      preserved. No technical adverse events occurred. At the one- to two-year follow
      up, complete resolution of clinical symptom had occurred in six patients and
      partial resolution in one. No recurrent aneurysm filling and no hemodynamic
      stenosis was observed. CONCLUSION: Endovascular reconstruction combining a
      covered stent with stent-assisted coiling could be an effective and safe strategy
      for the treatment of large cerebral aneurysms.

PMID- 25972388
TI  - Statistical modelling: essentially, all models are wrong, but some are useful.
      Review series on statistical modelling.

PMID- 25972389
TI  - A decision model for the watch-and-wait strategy in systemic sclerosis-associated
      interstitial lung disease.
AB  - OBJECTIVE: To develop a decision model to identify SSc-associated interstitial
      lung disease (ILD) patients who are eligible for watchful waiting at ILD
      diagnosis. METHODS: One hundred and fifty-one SSc-ILD patients who received
      medical care at Seoul National University Hospital from 1986 to 2013 were
      enrolled in this retrospective cohort study. ILD was diagnosed by chest CT.
      Patients with and without immunosuppressive treatment were compared in terms of
      characteristics at ILD diagnosis to identify distinguishing variables. After
      multivariate analysis, a decision model for watchful waiting was formulated. Its
      validity was assessed by comparing the survival of patients whose management in
      real practice did and did not accord with the management recommended by the
      model. RESULTS: The untreated group had better survival than the
      immunosuppressive treatment group (P = 0.0316, by log-rank test). The untreated
      group was less likely to have gastrointestinal involvement (P = 0.008) and
      pulmonary arterial hypertension (PAH), as determined by echocardiography) (P =
      0.015) and more likely to have favourable initial forced vital capacity (P =
      0.0004), favourable initial lung diffusion capacity for carbon monoxide (P =
      0.0002) and a low CT grade (P < 0.001). The final watchful waiting decision model
      included lack of PAH and limited ILD extent on CT. Application of the model to
      the cohort revealed that patients who were eligible for watchful waiting (as
      determined by the model) and underwent this management strategy had better
      survival than eligible patients who underwent immunosuppressive treatment (P =
      0.048, by log-rank test). CONCLUSION: Watchful waiting may be effective for SSc
      ILD patients who have minimal pulmonary involvement on CT and lack PAH on
      echocardiography at baseline.

PMID- 25972390
TI  - The influence of behavioural and psychological factors on medication adherence
      over time in rheumatoid arthritis patients: a study in the biologics era.
AB  - OBJECTIVES: To investigate levels of self-reported adherence to biologic
      treatment and establish the contribution of demographic, physical and
      psychological factors to biologic medication adherence in an RA cohort. METHODS:
      Adalimumab-treated patients were recruited through the British Society for
      Rheumatology Biologics Register for RA between May 2007 and April 2009.
      Demographic and baseline psychological measures including illness and medication
      beliefs were collected. Disease activity (28-item DAS), physical function (HAQ)
      and quality of life (36-item Short Form Health Survey) were also measured at
      baseline and at 6, 12 and 18 months. Adherence was assessed at each follow-up
      using the patient self-completed Compliance Questionnaire for Rheumatology (CQR).
      Multilevel mixed effects modelling analysis was performed to investigate
      predictors of adherence. RESULTS: Of the 329 Adalimumab-treated patients
      included, low adherence (CQR score <65) was reported in 23%, with 41% reporting
      low adherence at at least one time point. After controlling for age and disease
      duration, factors independently predictive of increased adherence were increased
      belief in medication necessity, with baseline effect diminishing over time [beta
      coefficient 1.68 (s.e. 0.19), P = 0.0001], lower medication concerns [0.50
      (0.15), P = 0.001], with this effect remaining throughout follow-up, increased
      professional or family member support [0.81 (0.32), P = 0.01], strong views of
      illness being chronic [0.32 (0.14), P = 0.025] and increased treatment control
      [0.41 (0.19), P = 0.032]. CONCLUSION: Wider recognition of the importance of
      psychological factors, particularly medication beliefs, in driving medication
      adherence could have substantial clinical and health economic benefits in RA. The
      psychological factors we have identified are putative targets for strategies to
      improve adherence in RA.

PMID- 25972391
TI  - International Consensus for ultrasound lesions in gout: results of Delphi process
      and web-reliability exercise.
AB  - OBJECTIVE: To produce consensus-based definitions of the US elementary lesions in
      gout and to test their reliability in a web-based exercise. METHODS: The process
      consisted of two steps. In the first step a written Delphi questionnaire was
      developed from a systematic literature review and expert international consensus.
      This collated information resulted in four statements defining US elementary
      lesions: double contour (DC), tophus, aggregates and erosion. The Delphi
      questionnaire was sent to 35 rheumatology experts in US, asking them to rate
      their level of agreement or disagreement with each statement. The second step
      tested the reliability by a web-exercise. US images of both normal and gouty
      elementary lesions were collected by the participants. A facilitator then
      constructed an electronic database of 110 images. The database was sent to the
      participants, who evaluated the presence/absence of US elementary lesions. A
      group of 20 images was displayed twice to evaluate intra-reader reliability.
      RESULTS: A total of 32 participants responded to the questionnaires. Good
      agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and
      erosion in the Delphi exercise after three rounds. The reliability on images
      showed inter-reader kappa values for DC, tophus, aggregates, erosion findings of
      0.98, 0.71, 0.54 and 0.85, respectively. The mean intra-reader kappa values were
      also acceptable: 0.93, 0.78, 0.65 and 0.78, respectively. CONCLUSION: This, the
      first consensus-based US definition of elementary lesions in gout, demonstrated
      good reliability overall. It constitutes an essential step in developing a core
      outcome measurement that permits a higher degree of homogeneity and comparability
      between multicentre studies.

PMID- 25972392
TI  - Use of arsenic trioxide in a hemodialysis-dependent patient with relapsed acute
      promyelocytic leukemia.
AB  - Arsenic trioxide has been established for use in both relapsed and front-line
      treatment of acute promyelocytic leukemia. Dose adjustments are recommended to be
      considered in severe renal impairment although dosage reduction guidelines are
      not provided. In addition, toxicities of arsenic are significant. The use of
      arsenic trioxide has not been well studied in dialysis patients and there is a
      paucity of data in the literature to support the use in such a situation. We
      describe an 81-year-old relapsed acute promyelocytic leukemia hemodialysis
      dependent patient with a pre-existing cardiac condition who was treated with 10
      mg arsenic trioxide three times weekly after dialysis. These findings provide
      support along with the marginal amount of currently published data for an arsenic
      trioxide dosing regimen in hemodialysis patients. 

PMID- 25972393
TI  - Dose estimations for Iranian 11-year-old pediatric phantoms undergoing computed
      tomography examinations.
AB  - In order to establish an organ and effective dose database for Iranian children
      undergoing computed tomography (CT) examinations, in the first step, two Iranian
      11-year-old phantoms were constructed from image series obtained from CT and
      magnetic resonance imaging (MRI). Organ and effective doses for these phantoms
      were calculated for head, chest, abdomen-pelvis and chest-abdomen-pelvis (CAP)
      scans at tube voltages of 80, 100 and 120 kVp, and then they were compared with
      those of the University of Florida (UF) 11-year-old male phantom. Depth
      distributions of the organs and the mass of the surrounding tissues located in
      the beam path, which shield the internal organs, were determined for all
      phantoms. From the results, it was determined that the main organs of the UF
      phantom receive smaller doses than the two Iranian phantoms, except for the
      urinary bladder of the Iranian girl phantom. In addition, the relationship
      between the anatomical differences and the size of the dose delivered was also
      investigated and the discrepancies between the results were examined and
      justified. 

PMID- 25972394
TI  - Neighborhood Influences and BMI in Urban Older Adults.
AB  - OBJECTIVE: Increases in body weight and declining physical activity that may
      accompany aging are linked to a range of problems affecting daily life (i.e.,
      decreased mobility and overall quality of life). This study investigates the
      actual and perceived neighborhood environment on overweight and obese urban older
      adults. METHOD: We selected 217 individuals aged 65+ who answered questions about
      their neighborhood on the 2009 Speak to Your Health survey. Using multinomial
      regression models and geospatial models, we examined relationships between
      neighborhood environment and BMI. RESULTS: We found that obese older adults were
      63% less likely to have a park within their neighborhood ( p = .04). Our results
      also show that older adults who perceive their neighborhood crime as very high
      are 12 times more likely to be overweight ( p = .04). DISCUSSION: Findings
      suggest that parks may affect BMI in older adults; however, neighborhood
      perceptions play a greater role.

PMID- 25972395
TI  - Endoscopic Versus "No-Touch" Saphenous Vein Harvesting for Coronary Artery Bypass
      Grafting: A Trade-Off Between Wound Healing and Graft Patency.
AB  - The advantage in terms of wound infection, wound healing, and scarring has
      resulted in the recent adoption of endoscopic vein harvesting (EVH) as a standard
      of care for coronary artery bypass grafting in some centers. However, concerns
      regarding the quality of these grafts have been raised after recent evidence of
      decreased graft patency, increased reoperation rate, and myocardial infarct,
      problems that are associated with vascular trauma caused when using this
      technique. Simultaneously, an atraumatic, "no-touch" technique for harvesting the
      saphenous vein was developed producing grafts with improved patency comparable to
      the internal thoracic artery. However, wound complications remain a problem using
      this technique. This review outlines the need to consider the poor graft quality
      that may result from EVH and raises the question what is likely to be the "best
      practice principle" in saphenous vein harvesting? 

PMID- 25972396
TI  - Serum Uric Acid and Prehypertension Among Adults Free of Cardiovascular Diseases
      and Diabetes: Baseline of the Brazilian Longitudinal Study of Adult Health (ELSA
      Brasil).
AB  - The association between serum uric acid (SUA) and prehypertension was evaluated
      in a racially admixed sample of civil servants aged 35 to 74 years, enrolled
      (2008-2010) in the Brazilian Longitudinal Study of Health (ELSA-Brasil). Of the
      15 105 patients who enrolled in the study, we analyzed 3412 after excluding those
      who reported previous cardiovascular diseases, diabetes, or hypertension; were
      heavy drinkers; or had a body mass index (BMI) >= 35 kg/m(2). Among the men,
      logistic regression, adjusted for age, race, income, birth weight, salt intake,
      insulin resistance, BMI, and renal function revealed odds ratios (ORs) and 95%
      confidence intervals (CIs) of prehypertension from the bottom quartile (referent)
      to the top quartile of SUA levels as follows: 0.84 (95% CI, 0.61-1.38), 0.97
      (0.71-1.34) and 1.44 (1.04-2.0; P for trend .01). Analyzing for 1-standard
      deviation of change in SUA, the ORs were 1.19 (1.06-1.32). This association
      persisted in the subgroup analysis consisting of patients who were white,
      overweight, with a high salt intake but with normal renal function, and without
      metabolic syndrome. No association was found among women. In conclusion, SUA
      levels were associated with prehypertension among men.

PMID- 25972398
TI  - Sol-gel processing of novel bioactive Mg-containing silicate scaffolds for
      alveolar bone regeneration.
AB  - Periodontal tissue regeneration is an important application area of biomaterials,
      given the large proportion of the population affected by periodontal diseases
      like periodontitis. The aim of this study was the synthesis of a novel porous
      bioceramic scaffold in the SiO2-CaO-MgO system with specific properties targeted
      for alveolar bone tissue regeneration using a modification of the traditional
      foam replica technique. Since bioceramic scaffolds are considered brittle,
      scaffolds were also coated with gelatin in order to increase their mechanical
      stability. Gelatin was chosen for its biocompatibility, biodegradability, low
      cost, and low immunogenicity. However, gelatin degrades very fast in water
      solutions. For this reason, two different cross-linking agents were evaluated.
      Genipin, a non-toxic gardenia extract and the chemical compound 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide (EDC) in combination with N-hydroxysuccinimide
      (NHS), which is also considered non-toxic. The results of the investigation
      indicated that all scaffolds presented an open, interconnected porosity and
      pores' sizes in the range of 300-600 MUm, fast apatite-forming ability,
      biocompatibility, and suitable mechanical stability. 

PMID- 25972399
TI  - Superior abstract-concept learning by Clark's nutcrackers (Nucifraga columbiana).
AB  - The ability to learn abstract relational concepts is fundamental to higher level
      cognition. In contrast to item-specific concepts (e.g. pictures containing trees
      versus pictures containing cars), abstract relational concepts are not bound to
      particular stimulus features, but instead involve the relationship between
      stimuli and therefore may be extrapolated to novel stimuli. Previous research
      investigating the same/different abstract concept has suggested that primates
      might be specially adapted to extract relations among items and would require
      fewer exemplars of a rule to learn an abstract concept than non-primate species.
      We assessed abstract-concept learning in an avian species, Clark's nutcracker
      (Nucifraga columbiana), using a small number of exemplars (eight pairs of the
      same rule, and 56 pairs of the different rule) identical to that previously used
      to compare rhesus monkeys, capuchin monkeys and pigeons. Nutcrackers as a group
      (N = 9) showed more novel stimulus transfer than any previous species tested with
      this small number of exemplars. Two nutcrackers showed full concept learning and
      four more showed transfer considerably above chance performance, indicating
      partial concept learning. These results show that the Clark's nutcracker, a
      corvid species well known for its amazing feats of spatial memory, learns the
      same/different abstract concept better than any non-human species (including non
      human primates) yet tested on this same task. 

PMID- 25972400
TI  - The molecular correlates of organ loss: the case of insect Malpighian tubules.
AB  - Malpighian tubules play an essential role in excretion, osmoregulation and
      immunity of most insects. Exceptionally, aphids lack Malpighian tubules,
      providing the opportunity to investigate the fate of genes expressed in an organ
      that has undergone evolutionary reduction and loss. Making use of the sequenced
      genomes of Drosophila melanogaster and the pea aphid Acyrthosiphon pisum, we
      demonstrated that more than 50% of Drosophila genes expressed specifically in the
      Malpighian tubules had orthologues in the pea aphid genome and that most of the
      pea aphid orthologues with detectable expression were identified in the gut
      transcriptome. Relative to the whole genome, genes functioning in amino acid
      metabolism are significantly over-represented among the pea aphid orthologues of
      Malpighian tubule genes, likely reflecting the central importance of amino acid
      acquisition and metabolism in aphids. This study demonstrates that the
      evolutionary loss of a key insect organ, the Malpighian tubules, has not been
      associated with the coupled loss of molecular functions. 

PMID- 25972401
TI  - Red clothing increases perceived dominance, aggression and anger.
AB  - The presence and intensity of red coloration correlate with male dominance and
      testosterone in a variety of animal species, and even artificial red stimuli can
      influence dominance interactions. In humans, red stimuli are perceived as more
      threatening and dominant than other colours, and wearing red increases the
      probability of winning sporting contests. We investigated whether red clothing
      biases the perception of aggression and dominance outside of competitive
      settings, and whether red influences decoding of emotional expressions.
      Participants rated digitally manipulated images of men for aggression and
      dominance and categorized the emotional state of these stimuli. Men were rated as
      more aggressive and more dominant when presented in red than when presented in
      either blue or grey. The effect on perceived aggression was found for male and
      female raters, but only male raters were sensitive to red as a signal of
      dominance. In a categorization test, images were significantly more often
      categorized as 'angry' when presented in the red condition, demonstrating that
      colour stimuli affect perceptions of emotions. This suggests that the colour red
      may be a cue used to predict propensity for dominance and aggression in human
      males. 

PMID- 25972402
TI  - Comparative Efficacy of Feline Leukemia Virus (FeLV) Inactivated Whole-Virus
      Vaccine and Canarypox Virus-Vectored Vaccine during Virulent FeLV Challenge and
      Immunosuppression.
AB  - Four vaccines for feline leukemia virus (FeLV) are available in the United
      States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV
      (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a
      live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were
      vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or
      PureVax recombinant FeLV (group B, n = 10). Group C (n = 11) comprised
      unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed
      and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia
      at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC.
      Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in
      group B, and 10 of 11 cats in group C. Group A was significantly protected
      compared to those in groups B (P < 0.013) and C (P < 0.0001). No difference was
      found between groups B and C (P > 0.063). The preventable fraction was 100% for
      group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were
      detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in
      group C. Nucleic acid loads were significantly lower in group A than in group C
      (P < 0.01). Group A had significantly lower proviral DNA loads than group B at
      weeks 6 to 9 (P < 0.02). The viral RNA loads were significantly lower in group A
      than in group B at weeks 7 to 9 (P < 0.01). The results demonstrate that Nobivac
      feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia
      and had significantly smaller amounts of proviral DNA and plasma viral RNA loads
      than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls. 

PMID- 25972403
TI  - Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for
      Syphilis.
AB  - The resurgence of syphilis in recent years has become a serious threat to public
      health worldwide, and the serological detection of specific antibodies against
      Treponema pallidum remains the most reliable method for laboratory diagnosis of
      syphilis. This study examined the performance of the recently launched HISCL anti
      Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high
      volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis
      positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially
      interfering samples, and 30 "borderline" samples and was compared head to head
      with the commercially available Lumipulse G TP-N. In this study, the HISCL anti
      TP assay was in perfect agreement with the applied testing algorithms with an
      overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The
      sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence
      interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively.
      Considering the excellent ease of use and automation, high throughput, and its
      favorable sensitivity and specificity, the HISCL anti-TP assay may represent a
      new choice for syphilis screening in high-volume laboratories. 

PMID- 25972404
TI  - Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2
      Specific Human Chimeric Monoclonal Antibodies.
AB  - Presently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen
      L2-reactive antibody is not well understood, and no serologic standard exists for
      L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078
      serum samples for HPV16 L2 reactivity, and these were obtained from four prior
      clinical studies: a population-based (n = 880) surveillance study with a high
      risk HPV DNA prevalence of 10.8%, a cohort study of women (n = 160) with high
      grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women
      with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod
      therapy combined with either photodynamic therapy (PDT) (n = 19) or vaccination
      with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n = 19). Sera
      were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA)
      and then Western blot. Seven of the 1,078 serum samples tested had L2-specific
      antibodies, but none were detectably neutralizing for HPV16. To develop a
      standard, we substituted human IgG1 sequences into conserved regions of two
      rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16
      L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These
      chimeric MAbs retained neutralizing activity and together reacted with 33/34
      clinically relevant HPV types tested. In conclusion, our inability to identify an
      HPV16 L2-specific neutralizing antibody response even in the sera of patients
      with active genital HPV disease suggests the subdominance of L2 protective
      epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for
      immunoassays to measure L2-specific human antibodies. 

PMID- 25972405
TI  - Vaccination with the ospA- and ospB-Negative Borrelia burgdorferi Strain 50772
      Provides Significant Protection against Canine Lyme Disease.
AB  - Beagles received placebo or ospA- and ospB-negative Borrelia burgdorferi before a
      tick challenge. A total of 28 (41%) ticks and skin biopsy specimens from each
      control dog (n = 10) contained B. burgdorferi. In contrast, 12 (19%) ticks
      recovered from the vaccine recipients (n = 10) were infected (P = 0.0077), and 5
      dogs yielded spirochetes from the skin biopsy specimens (P = 0.0325). In
      addition, 9 (90%) placebo recipients and 4 (40%) vaccine recipients developed
      joint abnormalities (P = 0.0573). Therefore, vaccination with the ospA- and ospB
      negative spirochete provided significant protection against Lyme disease. 

PMID- 25972407
TI  - Heterogeneity of clozapine-associated myocarditis: An opportunity for novel
      preventing strategies.

PMID- 25972406
TI  - Cross-Reactive Epitopes in Borrelia burgdorferi p66.
AB  - Epitope mapping of the p66 outer membrane protein of Borrelia burgdorferi
      revealed that the protein contains numerous cross-reactive linear epitopes
      recognized by serum antibody in the majority of individuals tested, regardless of
      Lyme disease history, limiting the usefulness of this antigen in Lyme disease
      serodiagnostic assays. 

PMID- 25972408
TI  - St John's wort - Is it safe in Bipolar Disorder?

PMID- 25972409
TI  - Prevalence and impact of comorbid alcohol use disorder in bipolar disorder: A
      prospective follow-up study.
AB  - OBJECTIVE: Alcohol use disorder may very well increase the likelihood of
      affective episodes in bipolar disorder, but prospective data on survival are
      inconsistent. METHOD: The authors examined the prevalence of alcohol use
      disorders and their impact on the risk of relapse. A total of 284 consecutively
      admitted International Classification of Diseases-10 bipolar I (n = 161) and II
      (n = 123) patients were followed up naturalistically over a period of 4 years.
      RESULTS: The prevalence of alcohol use disorders was higher in bipolar II
      disorder than in bipolar I disorder (26.8% vs 14.9%; chi(2) = 5.46, p = 0.019),
      with a global prevalence of alcohol use disorders of 20.1% in the whole sample. A
      total of 8.7% of bipolar I patients suffered from alcohol abuse and 6.2% from
      alcohol dependency, whereas 13% bipolar II patients had alcohol abuse and 13.8%
      alcohol dependency. Male bipolar subjects had a higher prevalence of alcohol use
      disorders than female patients (38.3% vs 12.8%; chi(2) = 21.84, p-value < 0.001).
      The presence of alcohol use disorders was associated with an increased risk of
      depressive relapse in bipolar I patients (Cox regression analysis hazard ratio =
      2.7, p = 0.005). The increased risk was not modulated by medication. CONCLUSION:
      Our data underline the negative long-term impact of alcohol use disorders on
      bipolar disorder with more depressive bipolar I episodes and the importance of
      its detection and treatment.

PMID- 25972410
TI  - Ileosigmoid knotting: a rare case report with review of literature?.
AB  - Ileosigmoid knotting (ISK) is a rare cause of intestinal obstruction in which
      loops of ileum and sigmoid colon wrap around each other. It is very uncommon in
      western world when compared with the African and Asian region. It is rapidly a
      progressive, fatal disease. Early diagnosis and intervention is the key of better
      outcome. We are reporting a case of 51-year-old male who presented with shock
      within 24 h of onset of symptoms. Exploratory laparotomy revealed ISK causing
      gangrene of ileum and sigmoid colon. In view of haemodynamic unstability, end
      ileostomy was done after excising gangrenous segments. The patient expired after
      2 weeks due to complications of short bowl syndrome. We are also tabulating all
      cases of ISK reported in the literature till date. 

PMID- 25972411
TI  - What else is hiding behind superior mesenteric artery syndrome?
AB  - The superior mesenteric artery syndrome (SMAS) is an uncommon condition in
      children. We describe a case of a 7-year-old boy with SMAS that occurred 3 years
      after a Deloyers' procedure for subtotal colonic Hirschsprung who was admitted
      for bilious vomit, abdominal pain and diarrhea due to unrecognized celiac
      disease. This case emphasize that SMAS in children needs a close medical and
      surgical follow-up to avoid an underestimation of early clinical signs unrelated
      to surgery. 

PMID- 25972412
TI  - Caecal perforation from TB and the Law of Laplace.
AB  - A 43-year-old man presented to the hospital with haemoptysis. When worked up, his
      history and examination were highly suggestive of pulmonary tuberculosis (TB). He
      subsequently developed a massive upper gastrointestinal bleed and underwent an
      emergency laparotomy, which revealed a massively dilated caecum measuring ~20 cm
      in diameter. The caecum had perforated due to acute decompensation of intestinal
      TB. Though common in developing countries, TB is rare in the UK, especially the
      intestinal kind. The most striking feature of this case is, however, the size of
      the caecal distension caused by the tubercular inflammation and subsequent
      perforation-something unheard of in the literature. This massive caecal
      distention would be explained by the Law of Laplace. In conclusion, massive
      distension and caecal perforation are possible consequences of intestinal TB,
      especially in the 48-72 h immediately after starting anti-tubercular therapy. 

PMID- 25972413
TI  - Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of
      Polymicrobial Traumatic Wound Infections.
AB  - Combat trauma wounds with invasive fungal infections (IFIs) are often
      polymicrobial with fungal and bacterial growth, but the impact of the wound
      microbiology on clinical outcomes is uncertain. Our objectives were to compare
      the microbiological features between IFI and non-IFI wounds and evaluate whether
      clinical outcomes differed among IFI wounds based upon mold type. Data from U.S.
      military personnel injured in Afghanistan with IFI wounds were examined. Controls
      were matched by the pattern/severity of injury, including blood transfusion
      requirements. Wound closure timing was compared between IFI and non-IFI control
      wounds (with/without bacterial infections). IFI wound closure was also assessed
      according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds
      (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined.
      The time to wound closure was longer for the IFI wounds (median, 16 days) than
      for the non-IFI controls with/without SSTIs (medians, 12 and 9 days,
      respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods
      was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs,
      respectively. Among the IFI wounds, times to wound closure were significantly
      longer for wounds with Mucorales growth than for wounds with non-Mucorales growth
      (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and
      Aspergillus spp. growth were compared, there was no significant difference in
      wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the
      presence of invasive molds (predominant types: order Mucorales, Aspergillus spp.,
      and Fusarium spp.) significantly prolonged the time to wound closure. Overall,
      the times to wound closure were longest for the IFI wounds with Mucorales growth.

PMID- 25972414
TI  - Rapid Whole-Genome Sequencing of Mycobacterium tuberculosis Isolates Directly
      from Clinical Samples.
AB  - The rapid identification of antimicrobial resistance is essential for effective
      treatment of highly resistant Mycobacterium tuberculosis. Whole-genome sequencing
      provides comprehensive data on resistance mutations and strain typing for
      monitoring transmission, but unlike for conventional molecular tests, this has
      previously been achievable only from cultures of M. tuberculosis. Here we
      describe a method utilizing biotinylated RNA baits designed specifically for M.
      tuberculosis DNA to capture full M. tuberculosis genomes directly from infected
      sputum samples, allowing whole-genome sequencing without the requirement of
      culture. This was carried out on 24 smear-positive sputum samples, collected from
      the United Kingdom and Lithuania where a matched culture sample was available,
      and 2 samples that had failed to grow in culture. M. tuberculosis sequencing data
      were obtained directly from all 24 smear-positive culture-positive sputa, of
      which 20 were of high quality (>20* depth and >90% of the genome covered).
      Results were compared with those of conventional molecular and culture-based
      methods, and high levels of concordance between phenotypical resistance and
      predicted resistance based on genotype were observed. High-quality sequence data
      were obtained from one smear-positive culture-negative case. This study
      demonstrated for the first time the successful and accurate sequencing of M.
      tuberculosis genomes directly from uncultured sputa. Identification of known
      resistance mutations within a week of sample receipt offers the prospect for
      personalized rather than empirical treatment of drug-resistant tuberculosis,
      including the use of antimicrobial-sparing regimens, leading to improved
      outcomes. 

PMID- 25972415
TI  - Use of the FilmArray System for Detection of Zaire ebolavirus in a Small Hospital
      in Bo, Sierra Leone.
AB  - Laboratories associated with small hospitals often have limited expertise,
      personnel, and equipment to rapidly identify rare and emerging infectious
      diseases. We describe the successful use of the FilmArray system for rapid
      detection of Ebola virus directly from clinical samples in 6 out of 83 tested
      subjects in a small health care center in Sierra Leone. 

PMID- 25972416
TI  - Simple Real-Time PCR and Amplicon Sequencing Method for Identification of
      Plasmodium Species in Human Whole Blood.
AB  - Malaria is the leading identifiable cause of fever in returning travelers.
      Accurate Plasmodium species identification has therapy implications for P. vivax
      and P. ovale, which have dormant liver stages requiring primaquine. Compared to
      microscopy, nucleic acid tests have improved specificity for species
      identification and higher sensitivity for mixed infections. Here, we describe a
      SYBR green-based real-time PCR assay for Plasmodium species identification from
      whole blood, which uses a panel of reactions to detect species-specific non-18S
      rRNA gene targets. A pan-Plasmodium 18S rRNA target is also amplified to allow
      species identification or confirmation by sequencing if necessary. An evaluation
      of assay accuracy, performed on 76 clinical samples (56 positives using thin
      smear microscopy as the reference method and 20 negatives), demonstrated clinical
      sensitivities of 95.2% for P. falciparum (20/21 positives detected) and 100% for
      the Plasmodium genus (52/52), P. vivax (20/20), P. ovale (9/9), and P. malariae
      (6/6). The sensitivity of the P. knowlesi-specific PCR was evaluated using spiked
      whole blood samples (100% [10/10 detected]). The specificities of the real-time
      PCR primers were 94.2% for P. vivax (49/52) and 100% for P. falciparum (51/51),
      P. ovale (62/62), P. malariae (69/69), and P. knowlesi (52/52). Thirty-three
      specimens were used to test species identification by sequencing the pan
      Plasmodium 18S rRNA PCR product, with correct identification in all cases. The
      real-time PCR assay also identified two samples with mixed P. falciparum and P.
      ovale infection, which was confirmed by sequencing. The assay described here can
      be integrated into a malaria testing algorithm in low-prevalence areas, allowing
      definitive Plasmodium species identification shortly after malaria diagnosis by
      microscopy. 

PMID- 25972417
TI  - Proton Nuclear Magnetic Resonance Spectroscopy as a Technique for Gentamicin Drug
      Susceptibility Studies with Escherichia coli ATCC 25922.
AB  - Antimicrobial drug susceptibility tests involving multiple time-consuming steps
      are still used as reference methods. Today, there is a need for the development
      of new automated instruments that can provide faster results and reduce operating
      time, reagent costs, and labor requirements. Nuclear magnetic resonance (NMR)
      spectroscopy meets those requirements. The metabolism and antimicrobial
      susceptibility of Escherichia coli ATCC 25922 in the presence of gentamicin have
      been analyzed using NMR and compared with a reference method. Direct incubation
      of the bacteria (with and without gentamicin) into the NMR tube has also been
      performed, and differences in the NMR spectra were obtained. The MIC, determined
      by the reference method found in this study, would correspond with the
      termination of the bacterial metabolism observed with NMR. Experiments carried
      out directly into the NMR tube enabled the development of antimicrobial drug
      susceptibility tests to assess the effectiveness of the antibiotic. NMR is an
      objective and reproducible method for showing the effects of a drug on the
      subject bacterium and can emerge as an excellent tool for studying bacterial
      activity in the presence of different antibiotic concentrations. 

PMID- 25972418
TI  - Multicenter Clinical Evaluation of the Novel Alere i Strep A Isothermal Nucleic
      Acid Amplification Test.
AB  - Rapid detection of group A beta-hemolytic streptococcus (GAS) is used routinely
      to help diagnose and treat pharyngitis. However, available rapid antigen
      detection tests for GAS have relatively low sensitivity, and backup testing is
      recommended in children. Newer assays are more sensitive yet require excessive
      time for practical point-of-care use as well as laboratory personnel. The Alere i
      strep A test is an isothermal nucleic acid amplification test designed to offer
      highly sensitive results at the point of care within 8 min when performed by
      nonlaboratory personnel. The performance of the Alere i strep A test was
      evaluated in a multicenter prospective trial in a Clinical Laboratory Improvement
      Amendments (CLIA)-waived setting in comparison to bacterial culture in 481
      children and adults. Compared to culture, the Aleri i strep A test had 96.0%
      sensitivity and 94.6% specificity. Discrepant results were adjudicated by PCR and
      found the Alere i strep A test to have 98.7% sensitivity and 98.5% specificity.
      Overall, the Alere i strep A test could provide a one-step, rapid, point-of-care
      testing method for GAS pharyngitis and obviate backup testing on negative
      results. 

PMID- 25972419
TI  - Detection of Group A Streptococcus in Pharyngeal Swab Specimens by Use of the
      AmpliVue GAS Isothermal Helicase-Dependent Amplification Assay.
AB  - We evaluated the clinical performance (sensitivity and specificity) of the
      AmpliVue group A Streptococcus (GAS) isothermal helicase-dependent amplification
      assay using 1,192 pharyngeal swab specimens. AmpliVue GAS assay results were
      compared to the results of routine throat cultures on selective streptococcal
      blood agar plates. The sensitivity and specificity of the AmpliVue GAS assay were
      98.3% (95% confidence interval [CI], 95 to 100%) and 93.2% (95% CI, 91 to 95%),
      respectively. 

PMID- 25972420
TI  - Evaluation of Unbiased Next-Generation Sequencing of RNA (RNA-seq) as a
      Diagnostic Method in Influenza Virus-Positive Respiratory Samples.
AB  - Unbiased nontargeted metagenomic RNA sequencing (UMERS) has the advantage to
      detect known as well as unknown pathogens and, thus, can significantly improve
      the detection of viral, bacterial, parasitic, and fungal sequences in public
      health settings. In particular, conventional diagnostic methods successfully
      identify the putative pathogenic agent in only 30% to 40% of respiratory
      specimens from patients with acute respiratory illness. Here, we applied UMERS to
      24 diagnostic respiratory specimens (bronchoalveolar lavage [BAL] fluid, sputum
      samples, and a swab) from patients with seasonal influenza infection and 5 BAL
      fluid samples from patients with pneumonia that tested negative for influenza to
      validate RNA sequencing as an unbiased diagnostic tool in comparison to
      conventional diagnostic methods. In addition to our comparison to PCR, we
      evaluated the potential to retrieve comprehensive influenza virus genomic
      information and the capability to detect known superinfecting pathogens. Compared
      to quantitative real-time PCR for influenza viral sequences, UMERS detected
      influenza viral sequences in 18 of 24 samples. Complete influenza virus genomes
      could be assembled from 8 samples. Furthermore, in 3 of 24 influenza-positive
      samples, additional viral pathogens could be detected, and 2 of 24 samples showed
      a significantly increased abundance of individual bacterial species known to
      cause superinfections during an influenza virus infection. Thus, analysis of
      respiratory samples from known or suspected influenza patients by UMERS provides
      valuable information that is relevant for clinical investigation. 

PMID- 25972422
TI  - Assessing Airway Microbiota in Cystic Fibrosis: What More Should Be Done?
AB  - The use of culture-independent methods has deepened our appreciation of the
      complexity of the bacterial communities that typically reside in the airways of
      persons with cystic fibrosis (CF). New insights into how changes in the structure
      of these communities relate to lung disease progression will likely raise
      expectations for more in-depth microbiologic analysis of CF respiratory
      specimens. An article in this issue of the Journal of Clinical Microbiology (W.
      G. Flight, A. Smith, C. Paisey, J. R. Marchesi, M. J. Bull, P. J. Norville, K. J.
      Mutton, A. K. Webb, R. J. Bright-Thomas, A. M. Jones, and E. Mahenthiralingam, J
      Clin Microbiol 53:2022-2029, 2015, http://dx.doi.org/10.1128/JCM.00432-15)
      describes the application of a culture-independent approach to the assessment of
      CF airway microbiota. 

PMID- 25972421
TI  - Rapid and Easy In Silico Serotyping of Escherichia coli Isolates by Use of Whole
      Genome Sequencing Data.
AB  - Accurate and rapid typing of pathogens is essential for effective surveillance
      and outbreak detection. Conventional serotyping of Escherichia coli is a
      delicate, laborious, time-consuming, and expensive procedure. With whole-genome
      sequencing (WGS) becoming cheaper, it has vast potential in routine typing and
      surveillance. The aim of this study was to establish a valid and publicly
      available tool for WGS-based in silico serotyping of E. coli applicable for
      routine typing and surveillance. A FASTA database of specific O-antigen
      processing system genes for O typing and flagellin genes for H typing was created
      as a component of the publicly available Web tools hosted by the Center for
      Genomic Epidemiology (CGE) (www.genomicepidemiology.org). All E. coli isolates
      available with WGS data and conventional serotype information were subjected to
      WGS-based serotyping employing this specific SerotypeFinder CGE tool.
      SerotypeFinder was evaluated on 682 E. coli genomes, 108 of which were sequenced
      for this study, where both the whole genome and the serotype were available. In
      total, 601 and 509 isolates were included for O and H typing, respectively. The O
      antigen genes wzx, wzy, wzm, and wzt and the flagellin genes fliC, flkA, fllA,
      flmA, and flnA were detected in 569 and 508 genome sequences, respectively.
      SerotypeFinder for WGS-based O and H typing predicted 560 of 569 O types and 504
      of 508 H types, consistent with conventional serotyping. In combination with
      other available WGS typing tools, E. coli serotyping can be performed solely from
      WGS data, providing faster and cheaper typing than current routine procedures and
      making WGS typing a superior alternative to conventional typing strategies. 

PMID- 25972424
TI  - Comparison of Inoculation with the InoqulA and WASP Automated Systems with Manual
      Inoculation.
AB  - The quality of sample inoculation is critical for achieving an optimal yield of
      discrete colonies in both monomicrobial and polymicrobial samples to perform
      identification and antibiotic susceptibility testing. Consequently, we compared
      the performance between the InoqulA (BD Kiestra), the WASP (Copan), and manual
      inoculation methods. Defined mono- and polymicrobial samples of 4 bacterial
      species and cloudy urine specimens were inoculated on chromogenic agar by the
      InoqulA, the WASP, and manual methods. Images taken with ImagA (BD Kiestra) were
      analyzed with the VisionLab version 3.43 image analysis software to assess the
      quality of growth and to prevent subjective interpretation of the data. A 3- to
      10-fold higher yield of discrete colonies was observed following automated
      inoculation with both the InoqulA and WASP systems than that with manual
      inoculation. The difference in performance between automated and manual
      inoculation was mainly observed at concentrations of >10(6) bacteria/ml.
      Inoculation with the InoqulA system allowed us to obtain significantly more
      discrete colonies than the WASP system at concentrations of >10(7) bacteria/ml.
      However, the level of difference observed was bacterial species dependent.
      Discrete colonies of bacteria present in 100- to 1,000-fold lower concentrations
      than the most concentrated populations in defined polymicrobial samples were not
      reproducibly recovered, even with the automated systems. The analysis of cloudy
      urine specimens showed that InoqulA inoculation provided a statistically
      significantly higher number of discrete colonies than that with WASP and manual
      inoculation. Consequently, the automated InoqulA inoculation greatly decreased
      the requirement for bacterial subculture and thus resulted in a significant
      reduction in the time to results, laboratory workload, and laboratory costs. 

PMID- 25972423
TI  - Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E
      Pneumococci.
AB  - The pneumococcus is a leading pathogen infecting children and adults. Safe,
      effective vaccines exist, and they work by inducing antibodies to the
      polysaccharide capsule (unique for each serotype) that surrounds the cell;
      however, current vaccines are limited by the fact that only a few of the nearly
      100 antigenically distinct serotypes are included in the formulations. Within the
      serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and
      common colonizers of the nasopharynx in children. Serotype 6E was first reported
      in 2004 but was thought to be rare; however, we and others have detected serotype
      6E among recent pneumococcal collections. Therefore, we analyzed a diverse data
      set of ~1,000 serogroup 6 genomes, assessed the prevalence and distribution of
      serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and
      investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B
      antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of
      all genomes were of serotype 6E, and they were recovered worldwide from healthy
      children and patients of all ages with pneumococcal disease. Four genetic
      lineages, three of which were multidrug resistant, described ~90% of the serotype
      6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B
      antibodies were able to elicit killing of serotype 6E pneumococci. We also
      revealed three major genetic clusters of serotype 6A capsular sequences,
      discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype
      switching. Therefore, while vaccines appear to offer protection against serotype
      6E, genetic variants may reduce vaccine efficacy in the longer term because of
      the emergence of serotypes that can evade vaccine-induced immunity. 

PMID- 25972425
TI  - Epizootiological Investigation of Getah Virus Infection among Racehorses in Japan
      in 2014.
AB  - To clarify the factors causing an outbreak in 2014 of Getah virus infection among
      racehorses at the Miho training center, Japan, we isolated virus strains and
      performed an epizootiological investigation of affected horses and related horse
      populations. Three Getah virus isolates were recovered from clinical samples, and
      one of them (14-I-605) was used in a virus-neutralizing test. Of the affected
      horses (n = 33), 20 (60.6%) were 2-year-olds. We investigated the histories of
      Getah virus vaccination of the affected horses and the whole population at the
      Miho training center. Among the 2-year-old population, the prevalence of the
      disease in horses that had been vaccinated once was 14.1%. This was significantly
      higher than that in horses that had been vaccinated twice or more (1.3%; P <
      0.01). Among horses that had entered the training center from farms in Ibaraki
      Prefecture surrounding the training center and from neighboring Chiba Prefecture,
      the rate of seropositivity for Getah virus was 13.0% in September 2014 and 42.9%
      in October 2014; that in the corresponding periods in 2010 and 2013 was 0%. In
      conclusion, we identified two possible causes of the outbreak of Getah virus
      infection in the training center in 2014: (i) the existence of susceptible horses
      that had received only one dose of vaccination before the outbreak and (ii)
      increased risk of exposure to the virus because of epizootic Getah virus
      infection among horses on surrounding farms in Ibaraki and Chiba prefectures. 

PMID- 25972426
TI  - Comparison of Sample Preparation Methods, Instrumentation Platforms, and
      Contemporary Commercial Databases for Identification of Clinically Relevant
      Mycobacteria by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass
      Spectrometry.
AB  - When mycobacteria are recovered in clinical specimens, timely species-level
      identification is required to establish the clinical significance of the isolate
      and facilitate optimization of antimicrobial therapy. Matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has
      recently been reported to be a reliable and expedited method for identification
      of mycobacteria, although various specimen preparation techniques and databases
      for analysis are reported across studies. Here we compared two MALDI-TOF MS
      instrumentation platforms and three databases: Bruker Biotyper Real Time
      Classification 3.1 (Biotyper), Vitek MS Plus Saramis Premium (Saramis), and Vitek
      MS v3.0. We evaluated two sample preparation techniques and demonstrate that
      extraction methods are not interchangeable across different platforms or
      databases. Once testing parameters were established, a panel of 157 mycobacterial
      isolates (including 16 Mycobacterium tuberculosis isolates) was evaluated,
      demonstrating that with the appropriate specimen preparation, all three methods
      provide reliable identification for most species. Using a score cutoff value of
      >=1.8, the Biotyper correctly identified 133 (84.7%) isolates with no
      misidentifications. Using a confidence value of >=90%, Saramis correctly
      identified 134 (85.4%) isolates with one misidentification and Vitek MS v3.0
      correctly identified 140 (89.2%) isolates with one misidentification. The levels
      of accuracy were not significantly different across the three platforms (P =
      0.14). In addition, we show that Vitek MS v3.0 requires modestly fewer repeat
      analyses than the Biotyper and Saramis methods (P = 0.04), which may have
      implications for laboratory workflow. 

PMID- 25972427
TI  - Competitive Homogeneous Immunoassay for Rapid Serodiagnosis of Hantavirus
      Disease.
AB  - In this study, we describe a competitive homogeneous immunoassay that makes use
      of Forster resonance energy transfer (FRET) in rapid detection of pathogen
      specific antibodies. The assay principle is based on competition between a
      monoclonal antibody (MAb) and serum antibodies to a given antigen. In the assay,
      named competitive FRET immunoassay (CFRET-IA), the FRET signal is induced if MAb
      carrying a donor label binds to an acceptor-labeled antigen. Specific antibodies
      in serum compete for antigen binding, resulting in reduced FRET signal. The proof
      of-principle for the assay was obtained using donor-labeled Puumala virus
      nucleocapsid protein (PUUV-N) and acceptor-labeled anti-PUUV-N MAb. The assay was
      evaluated by analyzing 329 clinical samples comprising 101 from individuals with
      acute PUUV infection, 42 from individuals with past infection, and 186 from
      individuals with PUUV-seronegative sera, and the results were compared to those
      of reference tests. The rapid serodiagnostic test we introduced herein performed
      with 100% sensitivity and 99% specificity for diagnosing acute hantavirus
      disease. 

PMID- 25972428
TI  - Use of Alternative Medications for Menopause-Related Symptoms in Three Major
      Ethnic Groups of Ipoh, Perak, Malaysia.
AB  - This cross-sectional study investigated the use of alternative medications to
      alleviate menopause-related symptoms among Malay, Chinese, and Indian women of
      Ipoh city. The prevalence, types, effectiveness, and associated factors were
      determined. The prevalence of alternative medication use was 41.4%. Evening
      primrose oil (EPO) was the most popular medication used (18.1%), followed by soy
      based products (12.3%), green tea (6.8%), and gingko (5.8%). The medication was
      reported to be highly effective by 58.3% of soya bean diet users and 41.1% of EPO
      users. Significant variables associated with the use were Chinese or Indian
      ethnicity (P < .001), age between 50 and 54 years (P < .01), lower self-health
      rating (P < .05), education level of diploma or professional degree (P < .05),
      employment as professionals or entrepreneurs (P < .05), and the use of hormone
      replacement therapy (P < .05). Regression analysis showed that Chinese and
      Indians had significantly higher odds for the use than Malays (Chinese: odds
      ratio [OR] = 4.33, 95% confidence interval [CI] = 2.392-7.837; Indians: OR =
      3.248, 95% CI = 1.586-6.654). 

PMID- 25972429
TI  - Iron Deficiency in Long-Term Parenteral Nutrition Therapy.
AB  - BACKGROUND: Iron is not routinely added to parenteral nutrition (PN) formulations
      in the United States because of the risk of anaphylaxis and concerns about
      incompatibilities. Studies have shown that iron dextran in non-lipid-containing
      PN solutions is safe. Data are limited on iron status, prevalence of iron
      deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term
      home PN (HPN). We aimed to determine the incidence of IDA and to examine the
      effectiveness of parenteral iron replacement in patients receiving HPN. METHODS:
      Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010
      were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and
      mean corpuscular volume (MCV) values were extracted. Response of iron indices to
      intravenous iron replacement was investigated. RESULTS: Of 185 patients (122
      women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18
      had unknown iron status before HPN. Of 93 patients who had sufficient iron
      storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months)
      of therapy. Iron was replaced by adding maintenance iron dextran to PN or by
      therapeutic iron infusion. Patients with both replacement methods had significant
      improvement in iron status. With intravenous iron replacement, mean ferritin
      increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from
      11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P =
      .007). CONCLUSIONS: Patients receiving HPN are susceptible to IDA. Iron
      supplementation should be addressed for patients who rely on PN.

PMID- 25972430
TI  - Glutamine Restores Tight Junction Protein Claudin-1 Expression in Colonic Mucosa
      of Patients With Diarrhea-Predominant Irritable Bowel Syndrome.
AB  - BACKGROUND: Recent studies showed that patients with diarrhea-predominant
      irritable bowel syndrome (IBS-D) had an increased intestinal permeability as well
      as a decreased expression of tight junctions. Glutamine, the major substrate of
      rapidly dividing cells, is able to modulate intestinal permeability and tight
      junction expression in other diseases. We aimed to evaluate, ex vivo, glutamine
      effects on tight junction proteins, claudin-1 and occludin, in the colonic mucosa
      of patients with IBS-D. MATERIALS AND METHODS: Twelve patients with IBS-D,
      diagnosed with the Rome III criteria, were included (8 women/4 men, aged 40.7 +/-
      6.9 years). Colonic biopsy specimens were collected and immediately incubated for
      18 hours in culture media with increasing concentrations of glutamine from 0.6-10
      mmol/L. Claudin-1 and occludin expression was then measured by immunoblot, and
      concentrations of cytokines were assessed by multiplex technology. Claudin-1
      expression was affected by glutamine (P < .05, analysis of variance). In
      particularly, 10 mmol/L glutamine increased claudin-1 expression compared with
      0.6 mmol/L glutamine (0.47 +/- 0.04 vs 0.33 +/- 0.03, P < .05). In contrast,
      occludin expression was not significantly modified by glutamine. Interestingly,
      glutamine effect was negatively correlated to claudin-1 (Pearson r = -0.83, P <
      .001) or occludin basal expression (Pearson r = -0.84, P < .001), suggesting that
      glutamine had more marked effects when tight junction protein expression was
      altered. Cytokine concentrations in culture media were not modified by glutamine
      treatment. CONCLUSION: Glutamine increased claudin-1 expression in the colonic
      mucosa of patients with IBS-D. In addition, glutamine effect seems to be
      dependent on basal expression of tight junction proteins.

PMID- 25972431
TI  - Characteristics of a Cohort of Home Parenteral Nutrition Patients at the Time of
      Enrollment in the Sustain Registry.
AB  - BACKGROUND: Home parenteral nutrition (HPN) is a vital lifesaving therapy for
      patients who are unable to maintain weight, fluid balance, nutrition, and
      functional status via oral or enteral nutrition alone. There are few current data
      sources describing HPN prevalence, patient demographics, or long-term outcomes in
      the United States. OBJECTIVE: To describe demographics and baseline
      characteristics of patients receiving HPN therapy. METHODS: This is a descriptive
      analysis of data from the first cohort of HPN patients at time of enrollment in
      the SustainTM Registry between August 2011 and February 2014. RESULTS: There were
      1251 patients enrolled from 29 sites. Eighty-five percent of patients were
      adults, with a mean age of 51.3 +/- 15.3 years. Fifteen percent were pediatric,
      with a mean age of 4.9 +/- 4.9 years. For both age groups, short-bowel syndrome
      was the most frequently reported HPN indication (24%). Adults most commonly had a
      peripherally inserted central catheter (47%) or a tunneled catheter (43%) for HPN
      administration. In contrast, most pediatric patients (72%) had a tunneled
      catheter. Most patients received parenteral nutrition daily and consumed some
      oral nutrition. Twenty-eight percent of all patients were expected to require HPN
      indefinitely. CONCLUSIONS: This is the first report of descriptive data from the
      Sustain Registry. The data reveal important characteristics of patients receiving
      HPN in 29 U.S. sites.

PMID- 25972432
TI  - Catheter Salvage After Catheter-Related Bloodstream Infection During Home
      Parenteral Nutrition.
AB  - BACKGROUND: Catheter-related bloodstream infection (CRBSI) is a common
      complication in patients receiving home parenteral nutrition (HPN). Data
      regarding catheter salvage after a CRBSI episode are limited. We aimed to
      determine the incidence of CRBSI and rates of catheter salvage in adult patients
      receiving HPN. MATERIALS AND METHODS: We retrospectively searched our
      prospectively maintained HPN database for the records of all adult patients
      receiving HPN from January 1, 1990, to December 31, 2013, at our tertiary
      referral center. Data abstracted from the medical records included demographics,
      diseases, treatments, and outcomes. The incidence of CRBSI and rates of catheter
      salvage were determined. RESULTS: Of 1040 patients identified, 620 (59.6%) were
      men. The median total duration on HPN was 124.5 days (interquartile range, 49.0
      345.5 days). Mean (SD) age at HPN initiation was 53.3 (15.3) years. During the
      study period, 465 CRBSIs developed in 187 patients (18%). The rate of CRBSI was
      0.64/1000 catheter days. Overall, 70% of catheters were salvaged (retained
      despite CRBSI) during the study period: 78% of infections with coagulase-negative
      staphylococci, 87% with methicillin-sensitive Staphylococcus aureus, and 27% with
      methicillin-resistant S aureus. The percentage of catheters salvaged was 63% from
      1990 to 1994, 63% from 1995 to 1999, 61% from 2000 to 2004, 72% from 2005 to
      2009, and 76% from 2010 to 2013. CONCLUSION: Catheter salvage is possible after a
      CRBSI episode. Since most episodes of CRBSI are caused by skin commensals,
      effective treatment without removal of the central venous catheter is possible in
      most cases.

PMID- 25972433
TI  - Mixed mechanisms of multi-site phosphorylation.
AB  - Multi-site phosphorylation is ubiquitous in cell biology and has been widely
      studied experimentally and theoretically. The underlying chemical modification
      mechanisms are typically assumed to be distributive or processive. In this paper,
      we study the behaviour of mixed mechanisms that can arise either because
      phosphorylation and dephosphorylation involve different mechanisms or because
      phosphorylation and/or dephosphorylation can occur through a combination of
      mechanisms. We examine a hierarchy of models to assess chemical information
      processing through different mixed mechanisms, using simulations, bifurcation
      analysis and analytical work. We demonstrate how mixed mechanisms can show
      important and unintuitive differences from pure distributive and processive
      mechanisms, in some cases resulting in monostable behaviour with simple dose
      response behaviour, while in other cases generating new behaviour-like
      oscillations. Our results also suggest patterns of information processing that
      are relevant as the number of modification sites increases. Overall, our work
      creates a framework to examine information processing arising from complexities
      of multi-site modification mechanisms and their impact on signal transduction. 

PMID- 25972434
TI  - The spatial profiles and metabolic capabilities of microbial populations impact
      the growth of antibiotic-resistant mutants.
AB  - Antibiotic resistance adversely affects clinical and public health on a global
      scale. Using the opportunistic human pathogen Pseudomonas aeruginosa, we show
      that increasing the number density of bacteria, on agar containing aminoglycoside
      antibiotics, can non-monotonically impact the survival of antibiotic-resistant
      mutants. Notably, at high cell densities, mutant survival is inhibited. A wide
      range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition
      results from the metabolic breakdown of amino acids, which results in alkaline by
      products. The consequent increase in pH acts in conjunction with aminoglycosides
      to mediate inhibition. Our work raises the possibility that the manipulation of
      microbial population structure and nutrient environment in conjunction with
      existing antibiotics could provide therapeutic approaches to combat antibiotic
      resistance.

PMID- 25972435
TI  - Cerebral oxygenation and optimal vascular brain organization.
AB  - The cerebral vascular network has evolved in such a way so as to minimize
      transport time and energy expenditure. This is accomplished by a subtle
      combination of the optimal arrangement of arteries, arterioles and capillaries
      and the transport mechanisms of convection and diffusion. Elucidating the
      interaction between cerebral vascular architectonics and the latter physical
      mechanisms can catalyse progress in treating cerebral pathologies such as stroke,
      brain tumours, dementia and targeted drug delivery. Here, we show that brain
      microvascular organization is predicated on commensurate intracapillary oxygen
      convection and parenchymal diffusion times. Cross-species grey matter results for
      the rat, cat, rabbit and human reveal very good correlation between the cerebral
      capillary and tissue mean axial oxygen convective and diffusion time intervals.
      These findings agree with the constructal principle.

PMID- 25972436
TI  - Semi-adaptive response and noise attenuation in bone morphogenetic protein
      signalling.
AB  - Temporal dynamics of morphogen-driven signalling events are critical for proper
      embryonic development. During development, cells translate extracellular bone
      morphogenetic protein (BMP) gradients, often subject to noise, into graded
      intracellular tail-phosphorylated SMAD (TP-SMAD) levels. Using modelling and
      experimental approaches, we found that BMPs induce TP-SMAD responses in neural
      precursor cells in a concentration-dependent manner, which are semi-adaptive
      within a specific intermediate range of BMP concentration. These semi-adaptive TP
      SMAD responses involve an intrinsically slow deactivation of BMP receptors, which
      attenuates noise by prolonging SMAD deactivation time after BMP withdrawal, but
      increases response time. Interestingly, negative feedback on BMP receptors is
      also required for semi-adaptation, which benefits both noise attenuation and
      response time, and therefore balances the trade-off seen with slow BMP receptor
      deactivation. These results highlight the rich dynamics of SMAD regulation in
      response to graded BMP concentration, and elucidate general design principles for
      balancing noise attenuation and activation speed in signalling systems.

PMID- 25972437
TI  - Scale-up of the production of highly reactive biogenic magnetite nanoparticles
      using Geobacter sulfurreducens.
AB  - Although there are numerous examples of large-scale commercial microbial
      synthesis routes for organic bioproducts, few studies have addressed the obvious
      potential for microbial systems to produce inorganic functional biomaterials at
      scale. Here we address this by focusing on the production of nanoscale
      biomagnetite particles by the Fe(III)-reducing bacterium Geobacter
      sulfurreducens, which was scaled up successfully from laboratory- to pilot plant
      scale production, while maintaining the surface reactivity and magnetic
      properties which make this material well suited to commercial exploitation. At
      the largest scale tested, the bacterium was grown in a 50 l bioreactor, harvested
      and then inoculated into a buffer solution containing Fe(III)-oxyhydroxide and an
      electron donor and mediator, which promoted the formation of magnetite in under
      24 h. This procedure was capable of producing up to 120 g of biomagnetite. The
      particle size distribution was maintained between 10 and 15 nm during scale-up of
      this second step from 10 ml to 10 l, with conserved magnetic properties and
      surface reactivity; the latter demonstrated by the reduction of Cr(VI). The
      process presented provides an environmentally benign route to magnetite
      production and serves as an alternative to harsher synthetic techniques, with the
      clear potential to be used to produce kilogram to tonne quantities.

PMID- 25972438
TI  - Regularity underlies erratic population abundances in marine ecosystems.
AB  - The abundance of a species' population in an ecosystem is rarely stationary,
      often exhibiting large fluctuations over time. Using historical data on marine
      species, we show that the year-to-year fluctuations of population growth rate
      obey a well-defined double-exponential (Laplace) distribution. This striking
      regularity allows us to devise a stochastic model despite seemingly irregular
      variations in population abundances. The model identifies the effect of reduced
      growth at low population density as a key factor missed in current approaches of
      population variability analysis and without which extinction risks are severely
      underestimated. The model also allows us to separate the effect of demographic
      stochasticity and show that single-species growth rates are dominantly determined
      by stochasticity common to all species. This dominance-and the implications it
      has for interspecies correlations, including co-extinctions-emphasizes the need
      for ecosystem-level management approaches to reduce the extinction risk of the
      individual species themselves.

PMID- 25972442
TI  - Associations between late and moderately preterm birth and smoking, alcohol, drug
      use and diet: a population-based case-cohort study.
AB  - OBJECTIVE: This study explores the associations between lifestyle factors and
      late and moderate preterm birth (LMPT: 32(+0)-36(+6) weeks' gestation), a
      relatively under-researched group. STUDY DESIGN: A population-based case-cohort
      study was undertaken involving 922 LMPT and 965 term (37+ weeks' gestation)
      singleton live and stillbirths born between 1 September 2009 and 31 December 2010
      to women residing in Leicestershire and Nottinghamshire, UK. Poisson
      multivariable regression models were fitted to estimate relative risks (RR) of
      LMPT birth associated with maternal smoking, alcohol and recreational drug use,
      and diet. RESULTS: Women who smoked during pregnancy were at 38% increased risk
      of LMPT birth compared with non-smokers (RR 1.38, 95% CI (1.04 to 1.84)). Low
      consumption of fruit and vegetables was associated with a 31% increased risk
      compared with those who reported eating higher consumption levels (RR 1.31 (1.03
      to 1.66)). Women who did not have any aspects of a Mediterranean diet were nearly
      twice as likely to deliver LMPT compared with those whose diet included more
      Mediterranean characteristics (RR 1.81 (1.04 to 3.14)). Women who smoked and
      consumed low levels of fruit and vegetables (5% of women) were at particularly
      high risk (RR=1.81 (1.29 to 2.55)). There was no significant effect of alcohol or
      recreational drug use on LMPT birth. CONCLUSIONS: Smoking and poor diet during
      pregnancy, factors that strongly impact on very preterm birth, are also important
      at later gestations and experienced together are associated with an elevated rate
      of risk. Our findings suggest early cessation of smoking during pregnancy may be
      an effective strategy to reduce LMPT births.

PMID- 25972440
TI  - Global regulation of heterochromatin spreading by Leo1.
AB  - Heterochromatin plays important roles in eukaryotic genome regulation. However,
      the repressive nature of heterochromatin combined with its propensity to self
      propagate necessitates robust mechanisms to contain heterochromatin within
      defined boundaries and thus prevent silencing of expressed genes. Here we show
      that loss of the PAF complex (PAFc) component Leo1 compromises chromatin
      boundaries, resulting in invasion of heterochromatin into flanking euchromatin
      domains. Similar effects are seen upon deletion of other PAFc components, but not
      other factors with related functions in transcription-associated chromatin
      modification, indicating a specific role for PAFc in heterochromatin regulation.
      Loss of Leo1 results in reduced levels of H4K16 acetylation at boundary regions,
      while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin
      suppresses heterochromatin spreading in leo1Delta cells, suggesting that Leo1
      antagonises heterochromatin spreading by promoting H4K16 acetylation. Our
      findings reveal a previously undescribed role for PAFc in regulating global
      heterochromatin distribution. 

PMID- 25972445
TI  - Pneumonia, septic arthritis, and brain abscesses in a construction worker.

PMID- 25972443
TI  - Cause-specific neonatal mortality: analysis of 3772 neonatal deaths in Nepal,
      Bangladesh, Malawi and India.
AB  - OBJECTIVE: Understanding the causes of death is key to tackling the burden of
      three million annual neonatal deaths. Resource-poor settings lack effective vital
      registration systems for births, deaths and causes of death. We set out to
      describe cause-specific neonatal mortality in rural areas of Malawi, Bangladesh,
      Nepal and rural and urban India using verbal autopsy (VA) data. DESIGN: We
      prospectively recorded births, neonatal deaths and stillbirths in seven
      population surveillance sites. VAs were carried out to ascertain cause of death.
      We applied descriptive epidemiological techniques and the InterVA method to
      characterise the burden, timing and causes of neonatal mortality at each site.
      RESULTS: Analysis included 3772 neonatal deaths and 3256 stillbirths. Between 63%
      and 82% of neonatal deaths occurred in the first week of life, and males were
      more likely to die than females. Prematurity, birth asphyxia and infections
      accounted for most neonatal deaths, but important subnational and regional
      differences were observed. More than one-third of deaths in urban India were
      attributed to asphyxia, making it the leading cause of death in this setting.
      CONCLUSIONS: Population-based VA methods can fill information gaps on the burden
      and causes of neonatal mortality in resource-poor and data-poor settings. Local
      data should be used to inform and monitor the implementation of interventions to
      improve newborn health. High rates of home births demand a particular focus on
      community interventions to improve hygienic delivery and essential newborn care.

PMID- 25972446
TI  - A Perspective on Studying G-Protein-Coupled Receptor Signaling with Resonance
      Energy Transfer Biosensors in Living Organisms.
AB  - The last frontier for a complete understanding of G-protein-coupled receptor
      (GPCR) biology is to be able to assess GPCR activity, interactions, and signaling
      in vivo, in real time within biologically intact systems. This includes the
      ability to detect GPCR activity, trafficking, dimerization, protein-protein
      interactions, second messenger production, and downstream signaling events with
      high spatial resolution and fast kinetic readouts. Resonance energy transfer
      (RET)-based biosensors allow for all of these possibilities in vitro and in cell
      based assays, but moving RET into intact animals has proven difficult. Here, we
      provide perspectives on the optimization of biosensor design, of signal detection
      in living organisms, and the multidisciplinary development of in vitro and cell
      based assays that more appropriately reflect the physiologic situation. In short,
      further development of RET-based probes, optical microscopy techniques, and mouse
      genome editing hold great potential over the next decade to bring real-time in
      vivo GPCR imaging to the forefront of pharmacology. 

PMID- 25972447
TI  - Rotational Symmetry of Two Pyrethroid Receptor Sites in the Mosquito Sodium
      Channel.
AB  - Voltage-gated sodium channels are the primary target of pyrethroid insecticides.
      Although it is well known that specific mutations in insect sodium channels
      confer knockdown resistance (kdr) to pyrethroids, the atomic mechanisms of
      pyrethroid-sodium channel interactions are not clearly understood. Previously,
      computer modeling and mutational analysis predicted two pyrethroid receptors,
      pyrethroid receptor site 1 (PyR1) (initial) and pyrethroid receptor site 2
      (PyR2), located in the domain interfaces II/III and I/II, respectively. The
      models differ in ligand orientation and the number of transmembrane helices
      involved. In this study, we elaborated a revised PyR1 model of the mosquito
      sodium channel. Computational docking in the Kv1.2-based open channel model
      yielded a complex in which a pyrethroid (deltamethrin) binds between the linker
      helix IIL45 and transmembrane helices IIS5, IIS6, and IIIS6 with its
      dibromoethenyl and diphenylether moieties oriented in the intra- and
      extracellular directions, respectively. The PyR2 and revised PyR1 models
      explained recently discovered kdr mutations and predicted new deltamethrin
      channel contacts. Further model-driven mutagenesis identified seven new
      pyrethroid-sensing residues, three in the revised PyR1 and four in PyR2. Our data
      support the following conclusions: 1) each pyrethroid receptor is formed by a
      linker-helix L45 and three transmembrane helices (S5 and two S6s); 2) IIS6
      contains four residues that contribute to PyR1 and another four to PyR2; 3) seven
      pairs of pyrethroid-sensing residues are located in symmetric positions within
      PyR1 and PyR2; and 4) pyrethroids bind to PyR1 and PyR2 in similar orientations,
      penetrating deeply into the respective domain interfaces. Our study elaborates
      the dual pyrethroid-receptor sites concept and provides a structural background
      for rational development of new insecticides. 

PMID- 25972448
TI  - The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the
      Periaqueductal Gray.
AB  - Emerging evidence indicates the involvement of GPR55 and its proposed endogenous
      ligand, lysophosphatidylinositol (LPI), in nociception, yet their role in central
      pain processing has not been explored. Using Ca(2+) imaging, we show here that
      LPI elicits concentration-dependent and GPR55-mediated increases in intracellular
      Ca(2+) levels in dissociated rat periaqueductal gray (PAG) neurons, which express
      GPR55 mRNA. This effect is mediated by Ca(2+) release from the endoplasmic
      reticulum via inositol 1,4,5-trisphosphate receptors and by Ca(2+) entry via P/Q
      type of voltage-gated Ca(2+) channels. Moreover, LPI depolarizes PAG neurons and
      upon intra-PAG microinjection, reduces nociceptive threshold in the hot-plate
      test. Both these effects are dependent on GPR55 activation, because they are
      abolished by pretreatment with ML-193 [N-(4-(N-(3,4-dimethylisoxazol-5
      yl)sulfamoyl)-phenyl)-6,8-dimethyl-2-(pyridin-2-yl)quinoline-4-carboxamide], a
      selective GPR55 antagonist. Thus, we provide the first pharmacological evidence
      that GPR55 activation at central levels is pronociceptive, suggesting that
      interfering with GPR55 signaling in the PAG may promote analgesia. 

PMID- 25972449
TI  - Direct Coupling of a Seven-Transmembrane-Span Receptor to a Galphai G-Protein
      Regulatory Motif Complex.
AB  - Group II activator of G-protein signaling (AGS) proteins contain one or more G
      protein regulatory motifs (GPR), which serve as docking sites for GalphaiGDP
      independent of Gbetagamma and stabilize the GDP-bound conformation of Galphai,
      acting as guanine nucleotide dissociation inhibitors. The GalphaGPR interaction
      is regulated by seven-transmembrane-spanning (7TM) receptors in the intact cell
      as determined by bioluminescence resonance energy transfer (BRET). It is
      hypothesized that a 7TM receptor directly couples to the GalphaGPR complex in a
      manner analogous to receptor coupling to the Galphabetagamma heterotrimer. As an
      initial approach to test this hypothesis, we used BRET to examine 7TM receptor
      mediated regulation of GalphaGPR in the intact cell when Galphai2 yellow
      fluorescent protein (YFP) was tethered to the carboxyl terminus of the alpha2A
      adrenergic receptor (alpha2AAR-Galphai2YFP). AGS3- and AGS4-Renilla luciferase
      (Rluc) exhibited robust BRET with the tethered GalphaiYFP, and this interaction
      was regulated by receptor activation localizing the regulation to the receptor
      microenvironment. Agonist regulation of the receptor-Galphai-GPR complex was also
      confirmed by coimmunoprecipitation and cell fractionation. The tethered Galphai2
      was rendered pertussis toxin-insensitive by a C352I mutation, and receptor
      coupling to endogenous Galphai/obetagamma was subsequently eliminated by cell
      treatment with pertussis toxin (PT). Basal and agonist-induced regulation of
      alpha2AAR-Galphai2YFP(C352I):AGS3Rluc and alpha2AAR-Galphai2YFP(C352I):AGS4Rluc
      BRET was not altered by PT treatment or Gbetagamma antagonists. Thus, the
      localized regulation of GalphaGPR by receptor activation appears independent of
      endogenous Galphai/obetagamma, suggesting that GalphaiAGS3 and GalphaiAGS4
      directly sense agonist-induced conformational changes in the receptor, as is the
      case for 7TM receptor coupling to the Galphabetagamma heterotrimer. The direct
      coupling of a receptor to the GalphaiGPR complex provides an unexpected platform
      for signal propagation with broad implications. 

PMID- 25972450
TI  - Tissue-nonspecific alkaline phosphatase as a target of sFRP2 in cardiac
      fibroblasts.
AB  - Recent studies of myocardial infarction in secreted Frizzled-related protein 2
      (sFRP2) knockout mice and our hamster heart failure therapy based on sFRP2
      blockade have established sFRP2 as a key profibrotic cytokine in the heart. The
      failing hamster heart is marked by prominent fibrosis and calcification with
      elevated expression of sFRP2. Noting the involvement of tissue-nonspecific
      alkaline phosphatase (TNAP) in bone mineralization and vascular calcification, we
      determined whether sFRP2 might be an upstream regulator of TNAP. Biochemical
      assays revealed an approximately twofold increase in the activity of TNAP and
      elevated levels of inorganic phosphate (Pi) in the failing heart compared with
      the normal heart. Neither was this change detected in the liver or hamstring
      muscle nor was it associated with systemic hyperphosphatemia. TNAP was readily
      cloned from the hamster heart and upon overexpression increased the level of
      extracellular but not intracellular Pi, which is consistent with the cell surface
      location of the ectoenzyme. In line with the previous demonstration that sFRP2
      blockade attenuated fibrosis, we show here that the therapy downregulated TNAP.
      This in vivo finding is corroborated by the in vitro study showing that cultured
      cardiac fibroblasts treated with recombinant sFRP2 protein exhibited progressive
      increase in the expression and activity of TNAP, which was completely abrogated
      by cycloheximide or tunicamycin. Induction of TNAP by sFRP2 is restricted to
      cardiac fibroblasts among the multiple cell types examined, and was not observed
      with sFRP4. The current work indicates that sFRP2 may promote cardiac
      fibrocalcification through coordinate activation of tolloid-like
      metalloproteinases and TNAP. 

PMID- 25972451
TI  - Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a
      membrane potential-driven organic anion transporter.
AB  - Membrane potential (Deltapsi)-driven and Cl(-)-dependent organic anion transport
      is a primary function of the solute carrier family 17 (SLC17) transporter family.
      Although the transport substrates and physiological relevance of the major
      members are well understood, SLC17A2 protein known to be Na(+)-phosphate
      cotransporter 3 (NPT3) is far less well characterized. In the present study, we
      investigated the transport properties and expression patterns of mouse SLC17A2
      protein (mNPT3). Proteoliposomes containing the purified mNPT3 protein took up
      radiolabeled p-aminohippuric acid (PAH) in a Deltapsi- and Cl(-)-dependent
      manner. The mNPT3-mediated PAH uptake was inhibited by 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDs) and Evans blue, common
      inhibitors of SLC17 family members. The PAH uptake was also inhibited by various
      anionic compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs
      (NSAIDs) and urate. Consistent with these observations, the proteoliposome took
      up radiolabeled urate in a Deltapsi- and Cl(-)-dependent manner.
      Immunohistochemistry with specific antibodies against mNPT3 combined with RT-PCR
      revealed that mNPT3 is present in various tissues, including the hepatic bile
      duct, luminal membranes of the renal urinary tubules, maternal side of
      syncytiotrophoblast in the placenta, apical membrane of follicle cells in the
      thyroid, bronchiole epithelial cells in the lungs, and astrocytes around blood
      vessels in the cerebrum. These results suggested that mNPT3 is a polyspecific
      organic anion transporter that is involved in circulation of urate throughout the
      body. 

PMID- 25972452
TI  - Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor
      desensitization in hypertension.
AB  - Prolonged vasoconstrictor-stimulated phospholipase C activity can induce arterial
      constriction, hypertension, and smooth muscle hypertrophy/hyperplasia. Arrestin
      proteins are recruited by agonist-occupied G protein-coupled receptors to
      terminate signaling and counteract changes in vascular tone. Here we determine
      whether the development of hypertension affects arrestin expression in resistance
      arteries and how such changes alter arterial contractile signaling and function.
      Arrestin2/3 expression was increased in mesenteric arteries of 12-wk-old
      spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto
      (WKY) controls, while no differences in arrestin expression were observed between
      6-wk-old SHR and WKY animals. In mesenteric artery myography experiments, high
      extracellular K(+)-stimulated contractions were increased in both 6- and 12-wk
      old SHR animals. Concentration-response experiments for uridine 5'-triphosphate
      (UTP) acting through P2Y receptors displayed a leftward shift in 12-wk, but not 6
      wk-old animals. Desensitization of UTP-stimulated vessel contractions was
      increased in 12-wk-old (but not 6-wk-old) SHR animals. Dual IP3/Ca(2+) imaging in
      mesenteric arterial cells showed that desensitization of UTP and endothelin-1
      (ET1) responses was enhanced in 12-wk-old (but not 6-wk-old) SHR compared with
      WKY rats. siRNA-mediated depletion of arrestin2 for UTP and arrestin3 for ET1,
      reversed the desensitization of PLC signaling. In conclusion, arrestin2 and 3
      expression is elevated in resistance arteries during the emergence of the early
      hypertensive phenotype, which underlies an enhanced ability to desensitize
      vasoconstrictor signaling and vessel contraction. Such regulatory changes may act
      to compensate for increased vasoconstrictor-induced vessel contraction. 

PMID- 25972453
TI  - Pyk and ERK your way to the hub by taking a RSK 2. Focus on "Regulation of NHE3
      by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2".

PMID- 25972454
TI  - Phase II double-blind placebo-controlled randomized study of armodafinil for
      brain radiation-induced fatigue.
AB  - BACKGROUND: Common acute-term side effects of brain radiotherapy (RT) include
      fatigue, drowsiness, decreased physical functioning, and decreased quality of
      life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known
      to reduce fatigue and increase cognitive function in breast cancer patients
      receiving chemotherapy) would result in reduced fatigue and sleepiness for
      patients receiving brain RT. METHODS: A phase II, multi-institutional, placebo
      controlled randomized trial assessed feasibility of armodafinil 150 mg/day in
      participants receiving brain RT, from whom we obtained estimates of variability
      for fatigue, sleepiness, QOL, cognitive function, and treatment effect. RESULTS:
      From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80%
      retention and 94% self-reported compliance. There were no grade 4-5 toxicities,
      and the incidence of grade 2-3 toxicities was similar between treatment arms, the
      most common of which were anxiety and nausea (15%), headaches (19%), and insomnia
      (20%). There were no statistically significant differences in end-RT or 4 week
      post-RT outcomes between armodafinil and placebo in any outcomes (Functional
      Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory,
      Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in
      participants with more baseline fatigue, those treated with armodafinil did
      better than those who received the placebo on the end-RT assessments for several
      outcomes. CONCLUSION: Armodafinil 150 mg/day was well tolerated in primary brain
      tumor patients undergoing RT with good compliance. While there was no overall
      significant effect on fatigue, those with greater baseline fatigue experienced
      improved QOL and reduced fatigue when using armodafinil. These data suggest that
      a prospective, phase III randomized trial is warranted for patients with greater
      baseline fatigue.

PMID- 25972456
TI  - Gauging heterogeneity in primary versus recurrent glioblastoma.

PMID- 25972455
TI  - Decreased affinity for efflux transporters increases brain penetrance and
      molecular targeting of a PI3K/mTOR inhibitor in a mouse model of glioblastoma.
AB  - BACKGROUND: Targeting drug delivery to invasive glioma cells is a particularly
      difficult challenge because these cells lie behind an intact blood-brain barrier
      (BBB) that can be observed using multimodality imaging. BBB-associated efflux
      transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein
      (BCRP) influence drug distribution to these cells and may negatively impact
      efficacy. To test the hypothesis that efflux transporters influence brain
      pharmacokinetics/pharmacodynamics of molecularly targeted agents in glioma
      treatment, we assessed region-specific penetrance and molecular-targeting
      capacity for a PI3K/mTOR kinase inhibitor that has high substrate affinity for
      efflux transporters (GDC-0980) and an analog (GNE-317) that was purposely
      designed to have reduced efflux. METHODS: Brain tumor penetrance of GDC-0980 and
      GNE-317 was compared between FVB/n wild-type mice and Mdr1a/b(-/-)Bcrp(-/-)
      triple-knockout mice lacking P-gp and BCRP. C57B6/J mice bearing intracranial
      GL261 tumors were treated with GDC-0980, GNE-317, or vehicle to assess the
      targeted pharmacokinetic/pharmacodynamic effects in a glioblastoma model.
      RESULTS: Animals treated with GNE-317 demonstrated 3-fold greater penetrance in
      tumor core, rim, and normal brain compared with animals dosed with GDC-0980.
      Increased brain penetrance correlated with decreased staining of activated p-Akt,
      p-S6, and p-4EBP1 effector proteins downstream of PI3K and mTOR. CONCLUSIONS: GDC
      0980 is subject to active efflux by P-gp and BCRP at the BBB, while brain
      penetrance of GNE-317 is independent of efflux, which translates into enhanced
      inhibition of PI3K/mTOR signaling. These data show that BBB efflux by P-gp and
      BCRP is therefore an important determinant in both brain penetrance and molecular
      targeting efficacy in the treatment of invasive glioma cells.

PMID- 25972457
TI  - The APJPH Supports "World No Tobacco Day".

PMID- 25972458
TI  - Prior infection exacerbates postoperative cognitive dysfunction in aged rats.
AB  - Older patients may experience persisting postoperative cognitive dysfunction
      (POCD), which is considered to largely depend on surgery-induced
      (neuro)inflammation. We hypothesize that inflammatory events before surgery could
      predispose patients to POCD. When part of our aged rats developed Mycoplasma
      pulmonis, this presented the unique opportunity to investigate whether a
      pulmonary infection before surgery influences surgery-induced neuroinflammation
      and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma
      infection (infection) and control rats (healthy) were subjected to abdominal
      surgery and jugular vein catheterization under general anesthesia (surgery) or
      remained naive (control). In postoperative week 2, behavioral tests were
      performed to assess cognitive performance and exploratory behavior. The acute
      systemic inflammatory response was investigated by measuring plasma IL-6 and IL
      12. In the hippocampus, prefrontal cortex and striatum, microglial activity,
      neurogenesis, and concentrations of IL-6, IL-12, IL1B, and brain-derived
      neurotropic factor on postoperative day 14 were determined. Rats still showed
      signs of increased neuroinflammatory activity, as well as cognitive and
      behavioral changes, 3 wk after the symptoms of infection had subsided. Rats that
      had experienced infection before surgery exhibited a more generalized and
      exacerbated postoperative cognitive impairment compared with healthy surgery
      rats, as well as a prolonged increase in systemic cytokine levels and increased
      microglial activation in the hippocampus and prefrontal cortex. These findings
      support the hypothesis that an infection before surgery under general anesthesia
      exacerbates POCD. Future studies are necessary to determine whether the found
      effects are aging specific and to investigate the magnitude and time course of
      this effect in a controlled manner. 

PMID- 25972459
TI  - Electroacupuncture with high frequency at acupoint ST-36 induces regeneration of
      lost enteric neurons in diabetic rats via GDNF and PI3K/AKT signal pathway.
AB  - Background electroacupuncture (EA) at acupoint ST-36 (Zusanli) has been used to
      alleviate gastrointestinal symptoms and improve gastrointestinal motility, but
      the effects and mechanisms of EA on enteric nervous system (ENS) have scarcely
      been investigated. SD rats were randomly divided into eight groups: normal
      control group, diabetes mellitus group (DM), chronic high-frequency EA (C-HEA),
      chronic low-frequency EA (C-LEA), chronic sham stimulation group (C-SEA), acute
      high-frequency EA group (A-HEA), acute low-frequency EA group (A-LEA), and
      diabetic with acute sham stimulation group (A-SEA). The parameters of HEA
      included a frequency of 100 Hz and an amplitude of 1 mA, while the parameters for
      LEA were 10 Hz and 1 mA. The expressions of PGP9.5, neuronal nitric oxide
      synthase neurons, CHAT neurons, glia cell line-derived neurotrophic factor (GDNF)
      and p-Akt were measured by immunofluorescence or immunohistochemistry, real-time
      PCR, and Western blotting methods in colon tissues of each rat. The total neurons
      and the two types of enteric neurons (neuronal nitric oxide synthase and choline
      acetyl transferase neurons), together with GDNF and p-Akt in the mRNA and protein
      level were significantly decreased in DM group compared with the normal control
      group in colon (P < 0.01). Compared with DM or all other DM with EA groups, the
      chronic HEA could induce a more significant quantitative increase in the mRNA and
      protein level of the enteric neurons and GDNF and p-Akt in colon (P < 0.01). EA
      with high-frequency and long-term stimuli at acupoint ST-36 can induce
      regeneration of lost enteric neurons in diabetic rats, and GDNF and PI3K/Akt
      signal pathway may play an important role in EA-induced regeneration of impaired
      enteric neurons. 

PMID- 25972460
TI  - IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon
      1.7 promoter in newborn male rat hippocampus.
AB  - Intrauterine growth restriction (IUGR) increases the risk for neurodevelopment
      delay and neuroendocrine reprogramming in both humans and rats. Neuroendocrine
      reprogramming involves the glucocorticoid receptor (GR) gene that is
      epigenetically regulated in the hippocampus. Using a well-characterized rodent
      model, we have previously shown that IUGR increases GR exon 1.7 mRNA variant and
      total GR expressions in male rat pup hippocampus. Epigenetic regulation of GR
      transcription may involve chromatin remodeling of the GR gene. A key chromatin
      remodeler is Brahma-related gene-1(Brg1), a member of the ATP-dependent
      SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Brg1
      regulates gene expression by affecting nucleosome repositioning and recruiting
      transcriptional components to target promoters. We hypothesized that IUGR would
      increase hippocampal Brg1 expression and binding to GR exon 1.7 promoter, as well
      as alter nucleosome positioning over GR promoters in newborn male pups. Further,
      we hypothesized that IUGR would lead to accumulation of specificity protein 1
      (Sp1) and RNA pol II at GR exon 1.7 promoter. Indeed, we found that IUGR
      increased Brg1 expression and binding to GR exon 1.7 promoter. We also found that
      increased Brg1 binding to GR exon 1.7 promoter was associated with accumulation
      of Sp1 and RNA pol II carboxy terminal domain pSer-5 (a marker of active
      transcription). Furthermore, the transcription start site of GR exon 1.7 was
      located within a nucleosome-depleted region. We speculate that changes in
      hippocampal Brg1 expression mediate GR expression and subsequently trigger
      neuroendocrine reprogramming in male IUGR rats. 

PMID- 25972462
TI  - Variable coloration is associated with dampened population fluctuations in
      noctuid moths.
AB  - Theory and recent reviews state that greater genetic and phenotypic variation
      should be beneficial for population abundance and stability. Experimental
      evaluations of this prediction are rare, of short duration and conducted under
      controlled environmental settings. The question whether greater diversity in
      functionally important traits stabilizes populations under more complex
      ecological conditions in the wild has not been systematically evaluated. Moths
      are mainly nocturnal, with a large variation in colour patterns among species,
      and constitute an important food source for many types of organisms. Here, we
      report the results of a long-term (2003-2013) monitoring study of 115 100 noctuid
      moths from 246 species. Analysis of time-series data provide rare evidence that
      species with higher levels of inter-individual variation in colour pattern have
      higher average abundances and undergo smaller between-year fluctuations compared
      with species having less variable colour patterns. The signature of interspecific
      temporal synchronization of abundance fluctuations was weak, suggesting that the
      dynamics were driven by species-specific biotic interactions rather than by some
      common, density-independent factor(s). We conclude that individual variation in
      colour patterns dampens population abundance fluctuations, and suggest that this
      may partly reflect that colour pattern polymorphism provides protection from
      visually oriented predators and parasitoids. 

PMID- 25972463
TI  - Adapting environmental management to uncertain but inevitable change.
AB  - Implementation of adaptation actions to protect biodiversity is limited by
      uncertainty about the future. One reason for this is the fear of making the wrong
      decisions caused by the myriad future scenarios presented to decision-makers. We
      propose an adaptive management (AM) method for optimally managing a population
      under uncertain and changing habitat conditions. Our approach incorporates
      multiple future scenarios and continually learns the best management strategy
      from observations, even as conditions change. We demonstrate the performance of
      our AM approach by applying it to the spatial management of migratory shorebird
      habitats on the East Asian-Australasian flyway, predicted to be severely impacted
      by future sea-level rise. By accounting for non-stationary dynamics, our solution
      protects 25,000 more birds per year than the current best stationary approach.
      Our approach can be applied to many ecological systems that require efficient
      adaptation strategies for an uncertain future.

PMID- 25972464
TI  - Biologically and diagenetically derived peptide modifications in moa collagens.
AB  - The modifications that occur on proteins in natural environments over time are
      not well studied, yet characterizing them is vital to correctly interpret
      sequence data recovered from fossils. The recently extinct moa (Dinornithidae) is
      an excellent candidate for investigating the preservation of proteins, their post
      translational modifications (PTMs) and diagenetic alterations during degradation.
      Moa protein extracts were analysed using mass spectrometry, and peptides from
      collagen I, collagen II and collagen V were identified. We also identified
      biologically derived PTMs (i.e. methylation, di-methylation, alkylation,
      hydroxylation, fucosylation) on amino acids at locations consistent with extant
      proteins. In addition to these in vivo modifications, we detected novel
      modifications that are probably diagenetically derived. These include loss of
      hydroxylation/glutamic semialdehyde, carboxymethyllysine and peptide backbone
      cleavage, as well as previously noted deamidation. Moa collagen sequences and
      modifications provide a baseline by which to evaluate proteomic studies of other
      fossils, and a framework for defining the molecular relationship of moa to other
      closely related taxa. 

PMID- 25972465
TI  - Natural selection on floral morphology can be influenced by climate.
AB  - Climate has the potential to influence evolution, but how it influences the
      strength or direction of natural selection is largely unknown. We quantified the
      strength of selection on four floral traits of the subalpine herb Ipomopsis sp.
      in 10 years that differed in precipitation, causing extreme temporal variation in
      the date of snowmelt in the Colorado Rocky Mountains. The chosen floral traits
      were under selection by hummingbird and hawkmoth pollinators, with hawkmoth
      abundance highly variable across years. Selection for flower length showed
      environmental sensitivity, with stronger selection in years with later snowmelt,
      as higher water resources can allow translation of pollination success into
      fitness based on seed production. Selection on corolla width also varied across
      years, favouring narrower corolla tubes in two unusual years with hawkmoths, and
      wider corollas in another late snowmelt year. Our results illustrate how changes
      in climate could alter natural selection even when the primary selective agent is
      not directly influenced. 

PMID- 25972466
TI  - Eliminating bovine tuberculosis in cattle and badgers: insight from a dynamic
      model.
AB  - Bovine tuberculosis (BTB) is a multi-species infection that commonly affects
      cattle and badgers in Great Britain. Despite years of study, the impact of
      badgers on BTB incidence in cattle is poorly understood. Using a two-host
      transmission model of BTB in cattle and badgers, we find that published data and
      parameter estimates are most consistent with a system at the threshold of
      control. The most consistent explanation for data obtained from cattle and badger
      populations includes within-host reproduction numbers close to 1 and between-host
      reproduction numbers of approximately 0.05. In terms of controlling infection in
      cattle, reducing cattle-to-cattle transmission is essential. In some regions,
      even large reductions in badger prevalence can have a modest impact on cattle
      infection and a multi-stranded approach is necessary that also targets badger-to
      cattle transmission directly. The new perspective highlighted by this two-host
      approach provides insight into the control of BTB in Great Britain. 

PMID- 25972467
TI  - Partner choice creates fairness in humans.
AB  - Many studies demonstrate that partner choice has played an important role in the
      evolution of human cooperation, but little work has tested its impact on the
      evolution of human fairness. In experiments involving divisions of money, people
      become either over-generous or over-selfish when they are in competition to be
      chosen as cooperative partners. Hence, it is difficult to see how partner choice
      could result in the evolution of fair, equal divisions. Here, we show that this
      puzzle can be solved if we consider the outside options on which partner choice
      operates. We conduct a behavioural experiment, run agent-based simulations and
      analyse a game-theoretic model to understand how outside options affect partner
      choice and fairness. All support the conclusion that partner choice leads to
      fairness only when individuals have equal outside options. We discuss how this
      condition has been met in our evolutionary history, and the implications of these
      findings for our understanding of other aspects of fairness less specific than
      preferences for equal divisions of resources. 

PMID- 25972468
TI  - Experimental taphonomy of Artemia reveals the role of endogenous microbes in
      mediating decay and fossilization.
AB  - Exceptionally preserved fossils provide major insights into the evolutionary
      history of life. Microbial activity is thought to play a pivotal role in both the
      decay of organisms and the preservation of soft tissue in the fossil record,
      though this has been the subject of very little experimental investigation. To
      remedy this, we undertook an experimental study of the decay of the brine shrimp
      Artemia, examining the roles of autolysis, microbial activity, oxygen diffusion
      and reducing conditions. Our findings indicate that endogenous gut bacteria are
      the main factor controlling decay. Following gut wall rupture, but prior to
      cuticle failure, gut-derived microbes spread into the body cavity, consuming
      tissues and forming biofilms capable of mediating authigenic mineralization, that
      pseudomorph tissues and structures such as limbs and the haemocoel. These
      observations explain patterns observed in exceptionally preserved fossil
      arthropods. For example, guts are preserved relatively frequently, while
      preservation of other internal anatomy is rare. They also suggest that gut
      derived microbes play a key role in the preservation of internal anatomy and that
      differential preservation between exceptional deposits might be because of
      factors that control autolysis and microbial activity. The findings also suggest
      that the evolution of a through gut and its bacterial microflora increased the
      potential for exceptional fossil preservation in bilaterians, providing one
      explanation for the extreme rarity of internal preservation in those animals that
      lack a through gut. 

PMID- 25972469
TI  - Perspective-taking abilities in the balance between autism tendencies and
      psychosis proneness.
AB  - Difficulties with the ability to appreciate the perspective of others
      (mentalizing) is central to both autism and schizophrenia spectrum disorders.
      While the disorders are diagnostically independent, they can co-occur in the same
      individual. The effect of such co-morbidity is hypothesized to worsen mentalizing
      abilities. The recent influential 'diametric brain theory', however, suggests
      that the disorders are etiologically and phenotypically diametrical, predicting
      opposing effects on one's mentalizing abilities. To test these contrasting
      hypotheses, we evaluated the effect of psychosis and autism tendencies on the
      perspective-taking (PT) abilities of 201 neurotypical adults, on the assumption
      that autism tendencies and psychosis proneness are heritable dimensions of normal
      variation. We show that while both autism tendencies and psychosis proneness
      induce PT errors, their interaction reduced these errors. Our study is, to our
      knowledge, the first to observe that co-occurring autistic and psychotic traits
      can exert opposing influences on performance, producing a normalizing effect
      possibly by way of their diametrical effects on socio-cognitive abilities. This
      advances the notion that some individuals may, to some extent, be buffered
      against developing either illness or present fewer symptoms owing to a balanced
      expression of autistic and psychosis liability. 

PMID- 25972470
TI  - Experimental reduction of intromittent organ length reduces male reproductive
      success in a bug.
AB  - It is now clear in many species that male and female genital evolution has been
      shaped by sexual selection. However, it has historically been difficult to
      confirm correlations between morphology and fitness, as genital traits are
      complex and manipulation tends to impair function significantly. In this study,
      we investigate the functional morphology of the elongate male intromittent organ
      (or processus) of the seed bug Lygaeus simulans, in two ways. We first use micro
      computed tomography (micro-CT) and flash-freezing to reconstruct in high
      resolution the interaction between the male intromittent organ and the female
      internal reproductive anatomy during mating. We successfully trace the path of
      the male processus inside the female reproductive tract. We then confirm that
      male processus length influences sperm transfer by experimental ablation and show
      that males with shortened processi have significantly reduced post-copulatory
      reproductive success. Importantly, male insemination function is not affected by
      this manipulation per se. We thus present rare, direct experimental evidence that
      an internal genital trait functions to increase reproductive success and show
      that, with appropriate staining, micro-CT is an excellent tool for investigating
      the functional morphology of insect genitalia during copulation. 

PMID- 25972471
TI  - Hearing conspecific vocal signals alters peripheral auditory sensitivity.
AB  - We investigated whether hearing advertisement calls over several nights, as
      happens in natural frog choruses, modified the responses of the peripheral
      auditory system in the green treefrog, Hyla cinerea. Using auditory evoked
      potentials (AEP), we found that exposure to 10 nights of a simulated male chorus
      lowered auditory thresholds in males and females, while exposure to random tones
      had no effect in males, but did result in lower thresholds in females. The
      threshold change was larger at the lower frequencies stimulating the amphibian
      papilla than at higher frequencies stimulating the basilar papilla.
      Suprathreshold responses to tonal stimuli were assessed for two peaks in the AEP
      recordings. For the peak P1 (assessed for 0.8-1.25 kHz), peak amplitude increased
      following chorus exposure. For peak P2 (assessed for 2-4 kHz), peak amplitude
      decreased at frequencies between 2.5 and 4.0 kHz, but remained unaltered at 2.0
      kHz. Our results show for the first time, to our knowledge, that hearing dynamic
      social stimuli, like frog choruses, can alter the responses of the auditory
      periphery in a way that could enhance the detection of and response to
      conspecific acoustic communication signals. 

PMID- 25972472
TI  - CD81 controls immunity to Listeria infection through rac-dependent inhibition of
      proinflammatory mediator release and activation of cytotoxic T cells.
AB  - Despite recent evidence on the involvement of CD81 in pathogen binding and Ag
      presentation by dendritic cells (DCs), the molecular mechanism of how CD81
      regulates immunity during infection remains to be elucidated. To investigate the
      role of CD81 in the regulation of defense mechanisms against microbial
      infections, we have used the Listeria monocytogenes infection model to explore
      the impact of CD81 deficiency in the innate and adaptive immune response against
      this pathogenic bacteria. We show that CD81(-/-) mice are less susceptible than
      wild-type mice to systemic Listeria infection, which correlates with increased
      numbers of inflammatory monocytes and DCs in CD81(-/-) spleens, the main subsets
      controlling early bacterial burden. Additionally, our data reveal that CD81
      inhibits Rac/STAT-1 activation, leading to a negative regulation of the
      production of TNF-alpha and NO by inflammatory DCs and the activation of
      cytotoxic T cells by splenic CD8alpha(+) DCs. In conclusion, this study
      demonstrates that CD81-Rac interaction exerts an important regulatory role on the
      innate and adaptive immunity against bacterial infection and suggests a role for
      CD81 in the development of novel therapeutic targets during infectious diseases. 

PMID- 25972473
TI  - The Notch signaling pathway controls short-lived effector CD8+ T cell
      differentiation but is dispensable for memory generation.
AB  - Following an infection, naive CD8(+) T cells expand and differentiate into two
      main populations of effectors: short-lived effector cells (SLECs) and memory
      precursor effector cells (MPECs). There is limited understanding of the molecular
      mechanism and cellular processes governing this cell fate. Notch is a key
      regulator of cell fate decision relevant in many immunological pathways. In this
      study, we add to the role of Notch in cell fate decision and demonstrate that the
      Notch signaling pathway controls the MPEC/SLEC differentiation choice following
      both Listeria infection and dendritic cell immunization of mice. Although fewer
      SLECs were generated, Notch deficiency did not alter the rate of memory CD8(+) T
      cell generation. Moreover, we reveal that the Notch signaling pathway plays a
      context-dependent role for optimal cytokine production by effector CD8(+) T
      cells. Together, our results unravel critical functions for the Notch signaling
      pathway during effector CD8(+) T cell differentiation.

PMID- 25972474
TI  - Characterization of a human platelet antigen-1a-specific monoclonal antibody
      derived from a B cell from a woman alloimmunized in pregnancy.
AB  - Human platelet Ag (HPA)-1a, located on integrin beta3, is the main target for
      alloantibodies responsible for fetal and neonatal alloimmune thrombocytopenia
      (FNAIT) in the white population. There are ongoing efforts to develop an Ab
      prophylaxis and therapy to prevent or treat FNAIT. In this study, an mAb specific
      for HPA-1a, named 26.4, was derived from an immortalized B cell from an
      alloimmunized woman who had an infant affected by FNAIT. It is the only HPA-1a
      specific human mAb with naturally paired H and L chains. Specific binding of mAb
      26.4, both native and recombinant forms, to platelets and to purified integrins
      alphaIIbbeta3 (from platelets) and alphaVbeta3 (from trophoblasts) from HPA-1a(+)
      donors was demonstrated by flow cytometry and surface plasmon resonance
      technology, respectively. No binding to HPA-1a(-) platelets or integrins was
      detected. Moreover, the Ab binds with higher affinity to integrin alphaVbeta3
      compared with a second HPA-1a-specific human mAb, B2G1. Further in vitro
      experimentation demonstrated that mAb 26.4 can opsonize HPA-1a(+) platelets for
      enhanced phagocytosis by monocytes, inhibit binding of maternal polyclonal anti
      HPA-1a Abs, and weakly inhibit aggregation of HPA-1a-heterozygous platelets, the
      latter with no predicted clinical relevance. Thus, mAb 26.4 is highly specific
      for HPA-1a and could potentially be explored for use as a prophylactic or
      therapeutic reagent for FNAIT intervention and as a phenotyping reagent to
      identify women at risk for immunization.

PMID- 25972475
TI  - Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin
      MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of
      otitis media.
AB  - Mucin overproduction is a hallmark of otitis media (OM). Streptococcus pneumoniae
      is one of the most common bacterial pathogens causing OM. Mucin MUC5AC plays an
      important role in mucociliary clearance of bacterial pathogens. However, if
      uncontrolled, excessive mucus contributes significantly to conductive hearing
      loss. Currently, there is a lack of effective therapeutic agents that suppress
      mucus overproduction. In this study, we show that a currently existing antistroke
      drug, vinpocetine, a derivative of the alkaloid vincamine, inhibited S.
      pneumoniae-induced mucin MUC5AC upregulation in cultured middle ear epithelial
      cells and in the middle ear of mice. Moreover, vinpocetine inhibited MUC5AC
      upregulation by inhibiting the MAPK ERK pathway in an MKP-1-dependent manner.
      Importantly, ototopical administration of vinpocetine postinfection inhibited
      MUC5AC expression and middle ear inflammation induced by S. pneumoniae and
      reduced hearing loss and pneumococcal loads in a well-established mouse model of
      OM. Thus, these studies identified vinpocetine as a potential therapeutic agent
      for inhibiting mucus production in the pathogenesis of OM.

PMID- 25972477
TI  - A CD153+CD4+ T follicular cell population with cell-senescence features plays a
      crucial role in lupus pathogenesis via osteopontin production.
AB  - Immune aging results in diminished adaptive immunity and increased risk for
      autoimmunity. We previously reported a unique PD-1(+) CD44(high)CD4(+) T cell
      population that increases with age in normal mice. In this study, we indicate
      that the age-dependent PD-1(+) CD44(high)CD4(+) T cells develop as unique T
      follicular (TF) cells in a B cell-dependent manner and consist of two
      subpopulations, as follows: CD153(+) cells preferentially secreting abundant
      osteopontin on TCR stimulation and CD153(-) cells that are apparently TCR
      anergic. These unique TF cells with essentially similar features increase much
      earlier and are accumulated in the spontaneous germinal centers (GCs) in lupus
      prone female BWF1 (f-BWF1) mice. These TF cells showed characteristic cell
      senescence features and developed in association with extensive CD4(+) T cell
      proliferation in vivo, suggesting replicative senescence. Although the CD153(+)
      TF cells were defective in proliferation capacity, they were quite stable and
      specifically responded to self GC-B cells to secret abundant osteopontin, which
      inhibited B cell receptor-induced GC-B cell apoptosis in f-BWF1 mice. Transfer of
      CD153(+) PD-1(+) CD4(+) T cells promoted the growth of spontaneous GCs, whereas
      administration of anti-osteopontin Ab suppressed GC enlargement and anti-nuclear
      Ab production and ameliorated clinical lupus nephritis of f-BWF1 mice. Current
      results suggest that senescent CD153(+) TF cells generated as a consequence of
      extensive endogenous CD4(+) T cell proliferation play an essential, if not
      sufficient, role in lupus pathogenesis in lupus-prone genetic background and may
      also contribute to an increased autoimmunity risk with age.

PMID- 25972476
TI  - Cutting edge: c-Kit signaling differentially regulates type 2 innate lymphoid
      cell accumulation and susceptibility to central nervous system demyelination in
      male and female SJL mice.
AB  - Multiple sclerosis preferentially affects women, and this sexual dimorphism is
      recapitulated in the SJL mouse model of multiple sclerosis, experimental
      autoimmune encephalomyelitis (EAE). In this study, we demonstrate that signaling
      through c-Kit exerts distinct effects on EAE susceptibility in male and female
      SJL mice. Previous studies in females show that Kit mutant (W/W(v)) mice are less
      susceptible to EAE than are wild-type mice. However, male W/W(v) mice exhibit
      exacerbated disease, a phenotype independent of mast cells and corresponding to a
      shift from a Th2- to a Th17-dominated T cell response. We demonstrate a
      previously undescribed deficit in c-Kit(+) type 2 innate lymphoid cells (ILC2s)
      in W/W(v) mice. ILC2s are also significantly reduced in EAE-susceptible wild-type
      females, indicating that both c-Kit signals and undefined male-specific factors
      are required for ILC2 function. We propose that deficiencies in Th2-promoting
      ILC2s remove an attenuating influence on the encephalitogenic T cell response and
      therefore increases disease susceptibility.

PMID- 25972478
TI  - Programmed death-1 controls T cell survival by regulating oxidative metabolism.
AB  - The coinhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis
      by negatively regulating T cell function and survival. Blockade of PD-1 increases
      the severity of graft-versus-host disease (GVHD), but the interplay between PD-1
      inhibition and T cell metabolism is not well studied. We found that both murine
      and human alloreactive T cells concomitantly upregulated PD-1 expression and
      increased levels of reactive oxygen species (ROS) following allogeneic bone
      marrow transplantation. This PD-1(Hi)ROS(Hi) phenotype was specific to
      alloreactive T cells and was not observed in syngeneic T cells during homeostatic
      proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and
      total cellular ROS levels, and PD-1-driven increases in ROS were dependent upon
      the oxidation of fatty acids, because treatment with etomoxir nullified changes
      in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels
      impaired T cell survival in a process reversed by antioxidants. Furthermore, PD-1
      driven changes in ROS were fundamental to establishing a cell's susceptibility to
      subsequent metabolic inhibition, because blockade of PD-1 decreased the efficacy
      of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates
      apoptosis in alloreactive T cells by increasing ROS in a process dependent upon
      the oxidation of fat. In addition, blockade of PD-1 undermines the potential for
      subsequent metabolic inhibition, an important consideration given the increasing
      use of anti-PD-1 therapies in the clinic. 

PMID- 25972479
TI  - Thymic low affinity/avidity interaction selects natural Th1 cells.
AB  - Identification of intrathymic eomesodermin(+) (Eomes(+)) CD4 T cells creates a
      novel idea that there is more than one way for the generation of innate CD4 T
      cells. Promyelocytic leukemia zinc finger protein(+) T cells and natural Th17
      cells are known to be generated by sensing a high and persistent TCR strength,
      whereas this is not the case for Eomes(+) CD4 T cells. These cells go through low
      level signal during the entire maturation pathway, which subsequently leads to
      induction of high susceptibility to cytokine IL-4. This event seems to be a major
      determinant for the generation of this type of cell. These T cells are
      functionally equivalent to Th1 cells that are present in the periphery, and this
      event takes place both in transgenic and in wild-type mice. There is additional
      evidence that this type of Eomes(+) innate CD4 T cell is also present in human
      cord blood.

PMID- 25972481
TI  - CD155 (PVR/Necl5) mediates a costimulatory signal in CD4+ T cells and regulates
      allergic inflammation.
AB  - Although Th1 and Th2 cells are known to be involved in allergic inflammatory
      diseases, the molecular mechanisms underlying their differentiation are
      incompletely understood. In this study, we identified CD155 as a costimulatory
      molecule on CD4(+) T cells. Importantly, CD155-mediated signaling induced Th1
      development in both humans and mice, as evidenced by production of IFN-gamma and
      upregulation of Tbx21 transcription; these effects were independent of IL-12 but
      dependent on NF-kappaB-induced autocrine IFN-gamma that triggered positive
      feedback via STAT1 activation. Mice genetically deficient in CD155 or treated
      with anti-CD155 Ab exhibited attenuated Th1-type contact hypersensitivity. Thus,
      CD155 plays an important regulatory role in helper T cell differentiation and
      allergic diseases. 

PMID- 25972480
TI  - Cryptococcal heat shock protein 70 homolog Ssa1 contributes to pulmonary
      expansion of Cryptococcus neoformans during the afferent phase of the immune
      response by promoting macrophage M2 polarization.
AB  - Numerous virulence factors expressed by Cryptococcus neoformans modulate host
      defenses by promoting nonprotective Th2-biased adaptive immune responses. Prior
      studies demonstrate that the heat shock protein 70 homolog, Ssa1, significantly
      contributes to serotype D C. neoformans virulence through the induction of
      laccase, a Th2-skewing and CNS tropic factor. In the present study, we sought to
      determine whether Ssa1 modulates host defenses in mice infected with a highly
      virulent serotype A strain of C. neoformans (H99). To investigate this, we
      assessed pulmonary fungal growth, CNS dissemination, and survival in mice
      infected with either H99, an SSA1-deleted H99 strain (Deltassa1), and a
      complement strain with restored SSA1 expression (Deltassa1::SSA1). Mice infected
      with the Deltassa1 strain displayed substantial reductions in lung fungal burden
      during the innate phase (days 3 and 7) of the host response, whereas less
      pronounced reductions were observed during the adaptive phase (day 14) and mouse
      survival increased only by 5 d. Surprisingly, laccase activity assays revealed
      that Deltassa1 was not laccase deficient, demonstrating that H99 does not require
      Ssa1 for laccase expression, which explains the CNS tropism we still observed in
      the Ssa1-deficient strain. Lastly, our immunophenotyping studies showed that Ssa1
      directly promotes early M2 skewing of lung mononuclear phagocytes during the
      innate phase, but not the adaptive phase, of the immune response. We conclude
      that Ssa1's virulence mechanism in H99 is distinct and laccase-independent. Ssa1
      directly interferes with early macrophage polarization, limiting innate control
      of C. neoformans, but ultimately has no effect on cryptococcal control by
      adaptive immunity.

PMID- 25972482
TI  - Poly(inosinic-cytidylic) acid-triggered exacerbation of experimental asthma
      depends on IL-17A produced by NK cells.
AB  - Viral infection of the respiratory tract represents the major cause of acute
      asthma exacerbations. dsRNA is produced as an intermediate during replication of
      respiratory viruses and triggers immune responses via TLR3. This study aimed at
      clarifying the mechanisms underlying TLR3 triggered exacerbation of experimental
      allergic asthma. The TLR3 ligand poly(inosinic-cytidylic) acid was applied
      intranasally to mice with already established experimental allergic asthma.
      Airway inflammation, cytokine expression, mucus production, and airway reactivity
      was assessed in wild-type, IL-17A, or IL-23p19-deficient, and in NK cell-depleted
      mice. Local application of poly(inosinic-cytidylic) acid exacerbated experimental
      allergic asthma in mice as characterized by enhanced release of proinflammatory
      cytokines, aggravated airway inflammation, and increased mucus production
      together with pronounced airway hyperresponsiveness. This was further associated
      with augmented production of IL-17 by Th17 cells and NK cells. Whereas
      experimental exacerbation could be induced in IL-23p19-deficient mice lacking
      mature, proinflammatory Th17 cells, this was not possible in mice lacking IL-17A
      or in NK cell-depleted animals. These experiments indicate a central role for IL
      17 derived from NK cells but not from Th17 cells in the pathogenesis of virus
      triggered exacerbation of experimental asthma.

PMID- 25972483
TI  - The frequency of naive and early-activated hapten-specific B cell subsets
      dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.
AB  - Translation of therapeutic vaccines for addiction, cancer, or other chronic
      noncommunicable diseases has been slow because only a small subset of immunized
      subjects achieved effective Ab levels. We hypothesize that individual variability
      in the number of naive and early-activated hapten-specific B cells determines
      postvaccination serum Ab levels and vaccine efficacy. Using a model vaccine
      against the highly abused prescription opioid oxycodone, the polyclonal B cell
      population specific for an oxycodone-based hapten (6OXY) was analyzed by flow
      cytometry paired with Ag-based magnetic enrichment. A higher frequency of 6OXY
      specific B cells in either spleen biopsies or blood, before and after
      immunization, correlated to subsequent greater oxycodone-specific serum Ab titers
      and their efficacy in blocking oxycodone distribution to the brain and oxycodone
      induced behavior in mice. The magnitude of 6OXY-specific B cell activation and
      vaccine efficacy was tightly correlated to the size of the CD4(+) T cell
      population. The frequency of enriched 6OXY-specific B cells was consistent across
      various mouse tissues. These data provide novel evidence that variations in the
      frequency of naive or early-activated vaccine-specific B and T cells can account
      for individual responses to vaccines and may predict the clinical efficacy of a
      therapeutic vaccine.

PMID- 25972484
TI  - Cutting edge: Role of osteopontin and integrin alphav in T cell-mediated anti
      inflammatory responses in endotoxemia.
AB  - The immune system is equipped with mechanisms that downregulate hyperinflammation
      to avoid collateral damage. We demonstrated recently that unprimed T cells
      downregulate macrophage TNF production through direct interaction with
      macrophages in the spleen during LPS endotoxemia. How T cell migration toward
      macrophages occurs upon LPS injection is still not clear. In this study, we
      demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration
      to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin
      levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T
      cell migration toward macrophages was observed 3 h after treatment.
      Neutralization of sOPN and blockade of its receptor, integrin alphav,
      significantly inhibited CD4(+) T cell migration and increased susceptibility to
      endotoxemia. Our study demonstrates that the sOPN/integrin alphav axis, which
      induces T cell chemotaxis toward macrophages, is critical for suppressing
      hyperinflammation during the first 3 h of endotoxemia.

PMID- 25972485
TI  - Concordance of increased B1 cell subset and lupus phenotypes in mice and humans
      is dependent on BLK expression levels.
AB  - Polymorphisms in the B lymphoid tyrosine kinase (BLK) gene have been associated
      with autoimmune diseases, including systemic lupus erythematosus, with risk
      correlating with reduced expression of BLK. How reduced expression of BLK causes
      autoimmunity is unknown. Using Blk(+/+) , Blk(+/-) , and Blk(-/-) mice, we show
      that aged female Blk(+/-) and Blk(-/-) mice produced higher anti-dsDNA IgG Abs
      and developed immune complex-mediated glomerulonephritis, compared with Blk(+/+)
      mice. Starting at young age, Blk(+/-) and Blk(-/-) mice accumulated increased
      numbers of splenic B1a cells, which differentiated into class-switched CD138(+)
      IgG-secreting B1a cells. Increased infiltration of B1a-like cells into the
      kidneys was also observed in aged Blk(+/-) and Blk(-/-) mice. In humans, we found
      that healthy individuals had BLK genotype-dependent levels of anti-dsDNA IgG Abs
      as well as increased numbers of a B1-like cell population, CD19(+)CD3(
      )CD20(+)CD43(+)CD27(+), in peripheral blood. Furthermore, we describe the
      presence of B1-like cells in the tubulointerstitial space of human lupus kidney
      biopsies. Taken together, our study reveals a previously unappreciated role of
      reduced BLK expression on extraperitoneal accumulation of B1a cells in mice, as
      well as the presence of IgG autoantibodies and B1-like cells in humans.

PMID- 25972486
TI  - Analysis of celiac disease autoreactive gut plasma cells and their corresponding
      memory compartment in peripheral blood using high-throughput sequencing.
AB  - Autoreactive IgA plasma cells (PCs) specific for the enzyme transglutaminase 2
      (TG2) are abundant in the small intestine of patients with active celiac disease
      (CD), and their number drops in patients treated by dietary gluten elimination.
      Little is known about their characteristics and their role in the disease. In
      this study, using high-throughput sequencing of the IgH V region (IGHV) genes, we
      have studied features of TG2-specific PCs and their related B cell clones in
      peripheral blood. We found that TG2-specific PCs from both untreated and treated
      patients have acquired lower number of somatic hypermutation and used focused
      IGHV repertoire with overrepresentation of the IGHV3-48, IGHV4-59, IGHV5-10-1,
      and IGHV5-51 gene segments. Furthermore, these PCs were clonally expanded and
      showed signs of affinity maturation. Lineage trees demonstrated shared clones
      between gut PCs and blood memory B cells, primarily IgAs. Some trees also
      involved IgG cells, suggesting that anti-TG2 IgA and IgG responses are related.
      Similarly to TG2-specific PCs, clonally related memory IgA B cells of blood
      showed lower mutation rates with biased usage of IGHV3-48 and IGHV5-51. Such
      memory cells were rare in peripheral blood, yet detectable in most patients
      assessed by production of anti-TG2 Abs in vitro following stimulation of cells
      from patients who had been on a long-term gluten-free diet. Thus, the Ab response
      to TG2 in CD, while maintaining its IGHV gene usage, is dynamically regulated in
      response to gluten exposure with a low degree of maintenance at both PC and
      memory B cell levels in patients in remission.

PMID- 25972489
TI  - Components separation technique is feasible for assisting delayed primary fascial
      closure of open abdomen.
AB  - BACKGROUND AND AIMS: The goal after open abdomen treatment is to reach primary
      fascial closure. Modern negative pressure wound therapy systems are sometimes
      inefficient for this purpose. This retrospective chart analysis describes the use
      of the 'components separation' method in facilitating primary fascial closure
      after open abdomen. MATERIAL AND METHODS: A total of 16 consecutive critically
      ill surgical patients treated with components separation during open abdomen
      management were analyzed. No patients were excluded. RESULTS: Primary fascial
      closure was achieved in 75% (12/16). Components separation was performed during
      ongoing open abdomen treatment in 7 patients and at the time of delayed primary
      fascial closure in 9 patients. Of the former, 3/7 (43%) patients reached primary
      fascial closure, whereas all 9 patients in the latter group had successful
      fascial closure without major complications (p = 0.019). CONCLUSION: Components
      separation is a useful method in contributing to successful primary fascial
      closure in patients treated for open abdomen. Best results were obtained when
      components separation was performed simultaneously with primary fascial closure
      at the end of the open abdomen treatment.

PMID- 25972487
TI  - Genetic vaccines to potentiate the effective CD103+ dendritic cell-mediated cross
      priming of antitumor immunity.
AB  - The development of effective cancer vaccines remains an urgent, but as yet unmet,
      clinical need. This deficiency is in part due to an incomplete understanding of
      how to best invoke dendritic cells (DC) that are crucial for the induction of
      tumor-specific CD8(+) T cells capable of mediating durable protective immunity.
      In this regard, elevated expression of the transcription factor X box-binding
      protein 1 (XBP1) in DC appears to play a decisive role in promoting the ability
      of DC to cross-present Ags to CD8(+) T cells in the therapeutic setting. Delivery
      of DNA vaccines encoding XBP1 and tumor Ag to skin DC resulted in increased IFN
      alpha production by plasmacytoid DC (pDC) from skin/tumor draining lymph nodes
      and the cross-priming of Ag-specific CD8(+) T cell responses associated with
      therapeutic benefit. Antitumor protection was dependent on cross-presenting
      Batf3(+) DC, pDC, and CD8(+) T cells. CD103(+) DC from the skin/tumor draining
      lymph nodes of the immunized mice appeared responsible for activation of Ag
      specific naive CD8(+) T cells, but were dependent on pDC for optimal
      effectiveness. Similarly, human XBP1 improved the capacity of human blood- and
      skin-derived DC to activate human T cells. These data support an important
      intrinsic role for XBP1 in DC for effective cross-priming and orchestration of
      Batf3(+) DC-pDC interactions, thereby enabling effective vaccine induction of
      protective antitumor immunity. 

PMID- 25972488
TI  - Involvement of the HCK and FGR src-family kinases in FCRL4-mediated immune
      regulation.
AB  - FCRL4 is an immunoregulatory receptor expressed by a subpopulation of memory B
      cells. These tissue-based cells express increased levels of the src-family
      kinases HCK and FGR. In this study, we investigate the roles of these src-family
      kinases in FCRL4-mediated immunoregulation of B cells in the context of
      previously unrecognized palmitoylation of the receptor. We observed enhanced
      phosphorylation of FCRL4 on tyrosine residues in the presence of the HCK p59 or
      FGR. This phosphorylation was markedly reduced in assays using a palmitoylation
      defective mutant of FCRL4. In reporter gene studies, we observe that FCRL4
      expression enhances CpG-mediated activation of NF-kappaB signaling. Surprisingly,
      using a reporter gene linked to activation of the MAPK substrate Elk-1 in
      response to Ag receptor ligation, we find that FCRL4 has inhibitory activity in
      cells coexpressing FGR but an activating function in cells coexpressing HCK p59.
      We provide evidence that in primary memory B cells, expression of FCRL4 leads to
      increased expression of IL-10 in the presence of FGR or HCK p59 in response to
      CpG, but increased levels of IFN-gamma only in the context of coexpression of
      FGR. Our study supports the specific requirement of HCK p59 and FGR src-family
      kinases for FCRL4-mediated immunomodulatory activity and indicates that
      palmitoylation serves as an additional level of regulatory control of FCRL4.

PMID- 25972490
TI  - Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized
      controlled trial.
AB  - OBJECTIVE: To study the efficacy and safety of low-dose oral tetrahydrocannabinol
      (THC) in the treatment of dementia-related neuropsychiatric symptoms (NPS).
      METHODS: This is a randomized, double-blind, placebo-controlled study. Patients
      with dementia and clinically relevant NPS were randomly assigned to receive THC
      1.5 mg or matched placebo (1:1) 3 times daily for 3 weeks. Primary outcome was
      change in Neuropsychiatric Inventory (NPI), assessed at baseline and after 14 and
      21 days. Analyses were based on intention-to-treat. RESULTS: Twenty-four patients
      received THC and 26 received placebo. NPS were reduced during both treatment
      conditions. The difference in reduction from baseline between THC and placebo was
      not significant (mean difference NPItotal: 3.2, 95% confidence interval [CI] -3.6
      to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation
      Inventory 4.6, 95% CI -3.0 to 12.2), quality of life (Quality of Life-Alzheimer's
      Disease -0.5, 95% CI -2.6 to 1.6), or activities of daily living (Barthel Index
      0.6, 95% CI -0.8 to 1.9). The number of patients experiencing mild or moderate
      adverse events was similar (THC, n = 16; placebo, n = 14, p = 0.36). No effects
      on vital signs, weight, or episodic memory were observed. CONCLUSIONS: Oral THC
      of 4.5 mg daily showed no benefit in NPS, but was well-tolerated, which adds
      valuable knowledge to the scarce evidence on THC in dementia. The benign adverse
      event profile of this dosage allows study of whether higher doses are efficacious
      and equally well-tolerated. CLASSIFICATION OF EVIDENCE: This study provides Class
      I evidence that for patients with dementia-related NPS, low-dose THC does not
      significantly reduce NPS at 21 days, though it is well-tolerated.

PMID- 25972492
TI  - MRI in acute stroke: Good times are coming.

PMID- 25972491
TI  - Side and time variability of intraepidermal nerve fiber density.
AB  - OBJECTIVE: To assess the right-to-left and short-term variability of
      intraepidermal nerve fiber density (IENFD) at the distal site of the leg.
      METHODS: Patients with possible or probable small fiber neuropathy (SFN) and
      healthy volunteers (HVs) underwent skin biopsies at the right and left distal
      leg. A subgroup of participants underwent follow-up biopsies 20 days later.
      Biopsies were immunostained by polyclonal anti-protein gene product 9.5
      antibodies, and IENFD was quantified in nonconsecutive sections following
      published guidelines by operators blinded to the participants' condition
      (diagnosis, side, and time of biopsy). Findings were referred to sex- and age
      adjusted normative values. RESULTS: Forty patients and 17 HVs underwent bilateral
      skin biopsies; 15 patients and 8 HVs underwent follow-up skin biopsies. Sural
      nerve and dorsal sural nerve conduction studies were normal in all participants.
      Interside IENFD did not differ both in patients (median 2.45 IENF/mm +/- 1.45 SD
      right; 2.2 IENF/mm +/- 1.32 SD left) and HVs (median 6.3 IENF/mm +/- 2.81 right;
      6.2 IENF/mm +/- 2.3 SD left). The right-to-left correlation coefficients were
      excellent (Pearson 0.95 in SFN and 0.97 in HVs). The analysis of IENFD at 20-day
      follow-up biopsy showed no difference between sides in both groups and yielded
      excellent correlation coefficients. CONCLUSIONS: The diagnosis of SFN can be
      reliably ascertained by unilateral skin biopsy at the distal site of the leg, and
      IENFD is not expected to vary within 3 weeks.

PMID- 25972493
TI  - Seizure localization using ictal phase-locked high gamma: A retrospective
      surgical outcome study.
AB  - OBJECTIVE: To determine whether resection of areas with evidence of intense,
      synchronized neural firing during seizures is an accurate indicator of
      postoperative outcome. METHODS: Channels meeting phase-locked high gamma (PLHG)
      criteria were identified retrospectively from intracranial EEG recordings (102
      seizures, 46 implantations, 45 patients). Extent of removal of both the seizure
      onset zone (SOZ) and PLHG was correlated with seizure outcome, classified as good
      (Engel class I or II, n = 32) or poor (Engel class III or IV, n = 13). RESULTS:
      Patients with good outcomes had significantly greater proportions of both SOZ and
      the first 4 (early) PLHG sites resected. Improved outcome classification was
      noted with early PLHG, as measured by the area under the receiver operating
      characteristic curves (PLHG 0.79, SOZ 0.68) and by odds ratios for resections
      including at least 75% of sites identified by each measure (PLHG 9.7 [95% CI: 2.3
      41.5], SOZ 5.3 [95% CI: 1.2-23.3]). Among patients with resection of at least 75%
      of the SOZ, 78% (n = 30) had good outcomes, increasing to 91% when the resection
      also included at least 75% of early PLHG sites (n = 22). CONCLUSIONS: This study
      demonstrates the localizing value of early PLHG, which is comparable to that
      provided by the SOZ. Incorporation of PLHG into the clinical evaluation may
      improve surgical efficacy and help to focus resections on the most critical
      areas.

PMID- 25972494
TI  - Screening with MRI for Accurate and Rapid Stroke Treatment: SMART.
AB  - OBJECTIVE: The objective of this study was to demonstrate the feasibility of
      timely multimodal MRI screening before thrombolysis in acute stroke patients.
      METHODS: Quality improvement processes were initiated in 2013 to reduce door-to
      needle (DTN) time at the 2 hospitals where the NIH stroke team provides clinical
      care. Acute ischemic stroke (AIS) patients who received IV tissue plasminogen
      activator (tPA) <=4.5 hours from last known normal were identified. Demographic
      and clinical characteristics and timing metrics were analyzed comparing the time
      periods before, during, and after the quality improvement processes. RESULTS:
      There were 157 patients treated with IV tPA for AIS during 2012-2013, of whom 135
      (86%) were screened with MRI. DTN time was significantly reduced by 40% during
      this period from a median of 93 minutes in the first half of 2012 to 55 minutes
      in the last half of 2013 (p < 0.0001) with a significant 4-fold increase in the
      proportion of treated patients with DTN time <=60 minutes from 13.0% to 61.5%,
      respectively (p < 0.00001). Improvement in DTN time was associated with reduced
      door-to-MRI time, and there were no differences in demographic or clinical
      characteristics (p = 0.21-0.76). CONCLUSIONS: It is feasible and practical to
      consistently and rapidly deliver IV tPA to AIS patients within national benchmark
      times using MRI as the routine screening modality. The processes used in the
      SMART (Screening with MRI for Accurate and Rapid Stroke Treatment) Study to
      reduce DTN time have the potential to be widely applicable to other hospitals.

PMID- 25972495
TI  - Testing the trajectory difference in a semi-parametric longitudinal model.
AB  - Motivated by a genetic investigation on the progressive decline in renal function
      in a clinical trial study of kidney disease, we develop a practical test for
      evaluating the group difference in trajectories under a semi-parametric modeling
      framework. For the temporal patterns or trajectories of longitudinal data, B
      splines are used to approximate the function non-parametrically. Such
      approximation asymptotically converts the problem of testing trajectory
      difference into the significance test of regression coefficients that can be
      simply estimated by generalized estimating equations. To select the optimal
      number of inner knots for B-splines, a cross-validation procedure is performed
      using the criterion of the generalized residual sum of squares. The new proposed
      test successfully detects a significant difference of underlying genetic impact
      on the progression of renal disease, which is not captured by the parametric
      approach.

PMID- 25972496
TI  - The Strategic Use of Antiretrovirals to Prevent HIV Infection: A Converging
      Agenda.
AB  - There is a clear convergence toward an overarching strategic use of
      antiretroviral drugs to prevent human immunodeficiency virus (HIV) infection.
      Four interventions-immediate antiretroviral therapy (ART) for the infected
      partner in a serodiscordant couple, preexposure prophylaxis (PrEP), prevention of
      mother-to-child transmission (PMTCT), and postexposure prophylaxis (PEP)-are all
      strongly recommended by the World Health Organization as effective ways to
      prevent HIV infection. For HIV-infected individuals, ART to protect an HIV
      uninfected partner and PMTCT are both part of an expanding list of
      recommendations for starting ART immediately to both treat and prevent HIV
      infection. For HIV-uninfected individuals, PrEP and PEP are increasingly being
      seen as related interventions, and there are compelling reasons to consider the
      provision of PEP as a potential gateway to PrEP. The effectiveness of each of
      these interventions depends on overcoming barriers to seeking services, adequate
      community understanding and engagement, high levels of access and uptake of
      services including HIV testing and counselling, and high levels of adherence. 

PMID- 25972497
TI  - World Health Organization Guidelines on Postexposure Prophylaxis for HIV:
      Recommendations for a Public Health Approach.
AB  - The 2014 World Health Organization (WHO) guidelines for postexposure prophylaxis
      (PEP) developed recommendations for PEP irrespective of exposure source in
      recognition of the need to simplify eligibility assessment and prescribing
      practices. Traditionally, separate PEP guidelines have been developed according
      to exposure type, with difference guidelines for occupational exposure,
      nonoccupational exposure, and sexual assault. Recognizing the need to improve
      uptake and completion rates for PEP, the WHO 2014 guideline does not
      differentiate between exposure sources, but rather provides recommendations
      across all exposures. Recommendations for simplifying prescribing approaches and
      supporting adherence are also provided. In translating this guidance into
      national PEP guidelines, countries are encouraged to consider the need to provide
      PEP in a way that maximizes uptake and completion rates. 

PMID- 25972498
TI  - Efficacy of HIV Postexposure Prophylaxis: Systematic Review and Meta-analysis of
      Nonhuman Primate Studies.
AB  - BACKGROUND: The efficacy of antiretrovirals as postexposure prophylaxis (PEP) to
      prevent viral acquisition was demonstrated in nonhuman primate models of human
      immunodeficiency virus (HIV) in the early 1990s. To complement the evidence base
      for efficacy of HIV PEP in humans, we systematically reviewed the published data
      on PEP efficacy across animal studies. METHODS: PubMed, Web of Science, and
      Embase were searched from inception to 31 May 2014 for randomized and
      nonrandomized studies reporting seroconversions among uninfected animals exposed
      to HIV or simian immunodeficiency virus, irrespective of route of exposure.
      Seroconversion risk data were pooled using random-effects models, and
      associations explored through meta-regression. RESULTS: Twenty-five studies (408
      primates) were included for review. The risk of serconversion was 89% lower among
      animals exposed to PEP compared with those that did not receive PEP (odds ratio,
      0.11 [95% confidence interval, .05-.23]). Heterogeneity was low (I(2) = 0.0%). In
      meta-regression, a significant association was found between timing of PEP and
      seroconversion and the use of tenofovir compared with other drugs. CONCLUSIONS:
      This review provides further evidence of the protective benefit of PEP in
      preventing HIV acquisition, and the importance of initiating PEP as early as
      possible following virus exposure.

PMID- 25972499
TI  - Choice of antiretroviral drugs for postexposure prophylaxis for adults and
      adolescents: a systematic review.
AB  - BACKGROUND: The choice of preferred regimens for human immunodeficiency virus
      postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data
      have become available regarding the safety and tolerability of newer
      antiretroviral drugs. We undertook a systematic review to assess the safety and
      efficacy of antiretroviral options for PEP to inform the World Health
      Organization guideline revision process. METHODS: Four databases were searched up
      to 1 June 2014 for studies reporting outcomes associated with specific PEP
      regimens. Data on PEP completion and discontinuation due to adverse events was
      extracted and pooled estimates were obtained using random-effects meta-analyses.
      RESULTS: Fifteen studies (1830 PEP initiations) provided evaluable information on
      2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10
      studies (1755 initiations) provided evaluable information on the third drug,
      which was usually a protease inhibitor. The overall quality of the evidence was
      rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95%
      confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen
      and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP
      discontinuation due to an adverse event was lower among people taking TDF-based
      PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For
      the 3-drug comparison, PEP completion rates were highest for the TDF-based
      regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI,
      43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+
      boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+
      lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to
      adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and
      highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%). CONCLUSIONS:
      The findings of this review provide evidence supporting the use of coformulated
      TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will
      depend on setting; for resource-limited settings, LPV/r is a reasonable choice,
      pending the improved availability of better-tolerated drugs with less potential
      for drug-drug interactions.

PMID- 25972500
TI  - Choice of antiretroviral drugs for postexposure prophylaxis for children: a
      systematic review.
AB  - BACKGROUND: This systematic review aimed to assess the safety and efficacy of
      antiretroviral options for postexposure prophylaxis (PEP). Recognizing the
      limited data on the safety and efficacy of antiretroviral drugs for PEP in
      children, this review was extended to include consideration of data on the use of
      antiretroviral drugs for treatment of infants and children living with human
      immunodeficiency virus. METHODS: The PEP literature was assessed to identify
      studies reporting safety and completion rates for children given PEP, and this
      information was complemented by safety and efficacy data for drugs used in
      antiretroviral therapy. The proportion of patients experiencing each outcome was
      calculated and data were pooled using random-effects meta-analysis. RESULTS:
      Three prospective cohort studies reported outcomes of children given zidovudine
      (ZDV) plus lamivudine (3TC) as a 2-drug PEP regimen. The proportion of children
      completing the full 28-day course of PEP was 64.0% (95% confidence interval [CI],
      41.2%-86.8%), whereas the proportion discontinuing due to adverse events was 4.5%
      (95% CI, .4%-8.6%). One randomized trial compared abacavir (ABC) plus lamivudine
      (3TC) and ZDV+3TC as part of a dual or triple first-line antiretroviral therapy
      regimen; this study showed better efficacy in the ABC-containing combinations and
      no difference in the time to first serious adverse event. Three randomized trials
      compared lopinavir/ritonavir (LPV/r) to nevirapine (NVP) for antiretroviral
      therapy and showed a lower risk of treatment discontinuations associated with
      LPV/r vs NVP (hazard ratio, 0.56 [95% CI, .41-.75]) but no difference in drug
      related adverse events. The overall quality of the evidence was rated as very
      low. CONCLUSIONS: This review supports ZDV+3TC+LPV/r as the preferred 3-drug
      regimen for PEP in children.

PMID- 25972501
TI  - Starter packs versus full prescription of antiretroviral drugs for postexposure
      prophylaxis: a systematic review.
AB  - BACKGROUND: The provision of starter packs for human immunodeficiency virus
      postexposure prophylaxis (PEP) is practiced in many settings to facilitate rapid
      initiation by nonexperts and encourage adherence. However, the impact of starter
      packs on PEP completion rates has not been systematically assessed. We
      systematically reviewed the evidence on outcomes associated with starter packs
      for PEP compared to full prescriptions. METHODS: Four databases and 2 conference
      abstract sites were searched up to December 2013; this search was updated in 1
      database in June 2014. PEP completion rates, stratified by prescribing practice,
      were pooled using random-effects meta-analysis. RESULTS: Fifty-four studies
      provided data on 11 714 PEP initiations. Thirty-seven studies, including 3
      randomized controlled trials (RCTs) and 34 observational cohorts, provided
      information on starter packs (although none of the RCTs specifically assessed
      starter packs), and 17 studies, including 2 RCTs and 15 observational cohorts,
      provided information on full prescriptions. Overall, outcomes were better when
      participants were offered a full 28-day course of PEP at initial presentation to
      healthcare, with fewer refusals (11.4% [95% confidence interval {CI}, 5.3%-17.5%]
      vs 22% [95% CI, 16.7%-28.1%]) and higher completion rates (70% [95% CI, 56.7%
      77.3%] vs 53.2% [95% CI, 44.4%-62.2%]). More than a quarter (28% [95% CI, 21.4%
      34.5%]) of individuals provided with a PEP starter pack failed to return for
      their subsequent appointment and therefore defaulted prior to receiving a full
      course of PEP. The quality of the evidence overall was rated as very low.
      CONCLUSIONS: The findings of this review suggest that starter packs do not
      improve adherence to PEP and may result in lower adherence and completion rates.

PMID- 25972502
TI  - Optimizing adherence to preexposure and postexposure prophylaxis: the need for an
      integrated biobehavioral approach.
AB  - Preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) has been shown
      to be effective in preventing transmission of human immunodeficiency virus (HIV).
      A dose-response relationship between adherence and HIV transmission is
      illustrated in the current PrEP literature, and adherence interventions for PrEP
      may be useful, although currently few effective programs have been developed and
      tested. There is a paucity of randomized controlled trials testing PEP adherence
      interventions, and further research is needed. We conclude by proposing the
      importance of tailoring adherence counseling to address psychosocial factors and
      mental health stressors that may negatively affect adherence. 

PMID- 25972503
TI  - End Users' Views and Preferences on Prescribing and Taking Postexposure
      Prophylaxis for Prevention of HIV: Methods to Support World Health Organization
      Guideline Development.
AB  - The 2014 World Health Organization guidelines for human immunodeficiency virus
      postexposure prophylaxis (PEP) are the first to combine recommendations for all
      populations and exposures. To inform the development of these guidelines, we
      gathered views of end users on key aspects of PEP provision. A mixed-methods
      approach was used to gather views from the populations for whom the guideline
      will be of relevance. Data gathered from an online survey, focus group
      discussions, and previously collected data from in-depth interviews with key
      populations were used to inform the development of recommendations, in particular
      where there is a paucity of evidence to assess the benefits and harms of an
      intervention. This was a successful method to gather end users' views and
      preferences; however, limitations exist in the generalizability and reliability
      of the evidence. Future guideline development processes should consider methods
      to include the views of end users to guide the decision-making process. 

PMID- 25972504
TI  - Postexposure Prophylaxis Against Human Immunodeficiency Virus (HIV): New
      Guidelines From the WHO: A Perspective.

PMID- 25972505
TI  - The Transition From Postexposure Prophylaxis to Preexposure Prophylaxis: An
      Emerging Opportunity for Biobehavioral HIV Prevention.
AB  - Although some individuals who present for antiretroviral postexposure prophylaxis
      (PEP) had a 1-time exposure to human immunodeficiency virus (HIV), others may be
      recurrently risky. Given that preexposure prophylaxis (PrEP) has been shown to be
      efficacious, identification of those individuals who present for PEP who might
      benefit from PrEP is important to decrease HIV acquisition in high-risk
      individuals. While inclusion criteria for PrEP have been developed, there is a
      paucity of data to help clinicians determine which PEP users are at highest risk
      for HIV acquisition and therefore should be offered PrEP. We will discuss the
      rationale for using PrEP after PEP use, and will focus on the assessment of PEP
      users who may benefit from PrEP. 

PMID- 25972506
TI  - Formulating the Future Research Agenda for Postexposure Prophylaxis for HIV:
      Methodological Challenges and Potential Approaches.
AB  - BACKGROUND: During a World Health Organization-convened Guideline Development
      Group meeting, recommendations for postexposure prophylaxis (PEP) for human
      immunodeficiency virus were made and research gaps identified. METHODS: We used
      the PEP clinical management pathway and the Grading of Evidence, Assessment,
      Development and Evaluation (GRADE) system as a framework to formulate future
      research questions, describe the most feasible study design, and identify
      potential biases. RESULTS: Three key study design formats were identified to
      address 12 research questions: (1) survey- and interview-driven research to
      identify barriers to access to PEP and related clinical care; (2) establishment
      of a global PEP registry to generate data to inform the choice of an optimal PEP
      drug regimen, record drug toxicities arising from specific PEP regimens, and
      track follow-up and linkage to care (including transition from PEP to preexposure
      prophylaxis); and (3) randomized controlled trials to determine the optimal
      adherence promotion strategies necessary for successful outcomes following PEP.
      CONCLUSIONS: Positioning key clinical and programmatic research questions within
      the GRADE framework facilitates the formulation of an evidence-based research
      agenda and future revisions of guidelines.

PMID- 25972507
TI  - Isolation, characterization, kinetics, and enzymatic and nonenzymatic
      microbicidal activities of a novel c-type lysozyme from plasma of Schistocerca
      gregaria (Orthoptera: Acrididae).
AB  - A protein, designated as Sgl, showing a muramidase lytic activity to the cell
      wall of the Gram-positive bacterium Micrococcus lysodeikticus was isolated for
      the first time from plasma of Escherichia coli-immunized fifth instar
      Schistocerca gregaria. The isolated Sgl was detected as a single protein band, on
      both native- and SDS-PAGE, has a molecular weight of ~15.7 kDa and an isoelectric
      point (pI) of ca 9.3 and its antiserum has specifically recognized its isolated
      form. Fifty-nine percentage of Sgl lytic activity was recovered in the isolated
      fractions and yielded ca 126-fold increase in specific activity than that of the
      crude. The partial N-terminal amino acid sequence of the Sgl has 55 and 40%
      maximum identity with Bombyx mori and Gallus gallus c-type lysozymes,
      respectively. The antibacterial activity against the Gram-positive and the Gram
      negative bacteria were comparatively stronger than that of the hen egg white
      lysozyme (HEWL). The detected Sgl poration to the inner membrane that reach a
      maximum ability after 3 h was suggested to operate as a nonenzymatic mechanism
      for Gram-negative bacterial cell lysis, as tested in a permease-deficient E.
      coli, ML-35 strain. Sgl showed a maximal muramidase activity at pH 6.2, 30-50
      degrees C, and 0.05 M Ca(2+) or Mg(2+); and has a Km of 0.5 MUg/ml and a Vmax of
      0.518 with M. lysodeikticus as a substrate. The Sgl displayed a chitinase
      activity against chitin with a Km of 0.93 mg/ml and a Vmax of 1.63. 

PMID- 25972508
TI  - Chronic kidney disease induced by adenine: a suitable model of growth retardation
      in uremia.
AB  - Growth retardation is a major manifestation of chronic kidney disease (CKD) in
      pediatric patients. The involvement of the various pathogenic factors is
      difficult to evaluate in clinical studies. Here, we present an experimental model
      of adenine-induced CKD for the study of growth failure. Three groups (n = 10) of
      weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD),
      and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen,
      creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous
      front advance as an index of longitudinal growth rate, growth plate
      histomorphometry, chondrocyte proliferative activity, bone structure, aorta
      calcifications, and kidney histology were analyzed. Results are means +/- SE. AD
      rats developed renal failure (serum urea nitrogen: 70 +/- 6 mg/dl and creatinine:
      0.6 +/- 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 +/- 31 pg/ml).
      Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 +/-
      4.8 g, control rats: 112.6 +/- 4.7 g, and PF rats: 60.0 +/- 3.8 g) and length (AD
      rats: 7.2 +/- 0.2 cm, control rats: 11.1 +/- 0.3 cm, and PF rats: 8.1 +/- 0.3 cm)
      gains as well as lower osseous front advances (AD rats: 141 +/- 13 MUm/day,
      control rats: 293 +/- 16 MUm/day, and PF rats: 251 +/- 10 MUm/day). The processes
      of chondrocyte maturation and proliferation were impaired in AD rats, as shown by
      lower growth plate terminal chondrocyte height (21.7 +/- 2.3 vs. 26.2 +/- 1.9 and
      23.9 +/- 1.3 MUm in control and PF rats) and proliferative activity index (AD
      rats: 30 +/- 2%, control rats: 38 +/- 2%, and PF rats: 42 +/- 3%). The bone
      primary spongiosa structure of AD rats was markedly disorganized. In conclusion,
      adenine-induced CKD in young rats is associated with growth retardation and
      disturbed endochondral ossification. This animal protocol may be a useful new
      experimental model to study growth in CKD. 

PMID- 25972510
TI  - Aberrant glomerular filtration of urokinase-type plasminogen activator in
      nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine.
AB  - In nephrotic syndrome, aberrant glomerular filtration of plasminogen and
      conversion to active plasmin in preurine are thought to activate proteolytically
      epithelial sodium channel (ENaC) and contribute to sodium retention and edema.
      The ENaC blocker amiloride is an off-target inhibitor of urokinase-type
      plasminogen activator (uPA) in vitro. It was hypothesized that uPA is abnormally
      filtered to preurine and is inhibited in urine by amiloride in nephrotic
      syndrome. This was tested by determination of Na(+) balance, uPA protein and
      activity, and amiloride concentration in urine from rats with puromycin
      aminonucleoside (PAN)-induced nephrotic syndrome. Urine samples from 6 adult and
      18 pediatric patients with nephrotic syndrome were analyzed for uPA activity and
      protein. PAN treatment induced significant proteinuria in rats which coincided
      with increased urine uPA protein and activity, increased urine protease activity,
      and total plasminogen/plasmin concentration and Na(+) retention. Amiloride (2
      mg.kg(-1).24 h(-1)) concentration in urine was in the range 10-20 MUmol/l and
      reduced significantly urine uPA activity, plasminogen activation, protease
      activity, and sodium retention in PAN rats, while proteinuria was not altered. In
      paired urine samples, uPA protein was significantly elevated in urine from
      children with active nephrotic syndrome compared with remission phase. In six
      adult nephrotic patients, urine uPA protein and activity correlated positively
      with 24 h urine protein excretion. In conclusion, nephrotic syndrome is
      associated with aberrant filtration of uPA across the injured glomerular barrier.
      Amiloride inhibits urine uPA activity which attenuates plasminogen activation and
      urine protease activity in vivo. Urine uPA is a relevant target for amiloride in
      vivo. 

PMID- 25972509
TI  - Incipient renal transplant dysfunction associates with tubular syndecan-1
      expression and shedding.
AB  - Syndecan-1 is a transmembrane heparan sulfate proteoglycan involved in
      regenerative growth and cellular adhesion. We hypothesized that the induction of
      tubular syndecan-1 is a repair response to incipient renal damage in apparently
      stable, uncomplicated renal transplant recipients. We quantified tubular syndecan
      1 in unselected renal protocol biopsies taken 1 yr after transplantation.
      Spearman rank correlation analysis revealed an inverse correlation between
      tubular syndecan-1 expression and creatinine clearance at the time of biopsy (r =
      -0.483, P < 0.03). In a larger panel of protocol and indication biopsies from
      renal transplant recipients, tubular syndecan-1 correlated with tubular
      proliferation marker Ki67 (r = 0.518, P < 0.0001). In a rat renal transplantation
      model, 2 mo after transplantation, mRNA expression of syndecan-1 and its major
      sheddase, A disintegrin and metalloproteinase-17, were upregulated (both P <
      0.03). Since shed syndecan-1 might end up in the circulation, in a stable cross
      sectional human renal transplant population (n = 510), we measured plasma
      syndecan-1. By multivariate regression analysis, we showed robust independent
      associations of plasma syndecan-1 with renal (plasma creatinine and plasma urea)
      and endothelial function parameters (plasma VEGF-A, all P < 0.01). By various
      approaches, we were not able to localize syndecan-1 in vessel wall or endothelial
      cells, which makes shedding of syndecan-1 from the endothelial glycocalyx
      unlikely. Our data suggest that early damage in transplanted kidneys induces
      repair mechanisms within the graft, namely, tubular syndecan-1 expression for
      tubular regeneration and VEGF production for endothelial repair. Elevated plasma
      syndecan-1 levels in renal transplantation patients might be interpreted as
      repair/survival factor related to loss of tubular and endothelial function in
      transplanted kidneys. 

PMID- 25972511
TI  - Continence and micturition: physiological mechanisms under behavioral control.

PMID- 25972512
TI  - Adaptation by the collecting duct to an exogenous acid load is blunted by
      deletion of the proton-sensing receptor GPR4.
AB  - We previously reported that the deletion of the pH sensor GPR4 causes a non-gap
      metabolic acidosis and defective net acid excretion (NAE) in the GPR4 knockout
      mouse (GPR4-/-) (Sun X, Yang LV, Tiegs BC, Arend LJ, McGraw DW, Penn RB, and
      Petrovic S. J Am Soc Nephrol 21: 1745-1755, 2010). Since the major regulatory
      site of NAE in the kidney is the collecting duct (CD), we examined acid-base
      transport proteins in intercalated cells (ICs) of the CD and found comparable
      mRNA expression of kidney anion exchanger 1 (kAE1), pendrin, and the a4 subunit
      of H(+)-ATPase in GPR4-/- vs. +/+. However, NH4Cl loading elicited adaptive
      doubling of AE1 mRNA in GPR4+/+, but a 50% less pronounced response in GPR4-/-.
      In GPR4+/+, NH4Cl loading evoked a cellular response characterized by an increase
      in AE1-labeled and a decrease in pendrin-labeled ICs similar to what was reported
      in rabbits and rats. This response did not occur in GPR4-/-. Microperfusion
      experiments demonstrated that the activity of the basolateral Cl(-)/HCO3(-)
      exchanger, kAE1, in CDs isolated from GPR4-/- failed to increase with NH4Cl
      loading, in contrast to the increase observed in GPR4+/+. Therefore, the
      deficiency of GPR4 blunted, but did not eliminate the adaptive response to an
      acid load, suggesting a compensatory response from other pH/CO2/bicarbonate
      sensors. Indeed, the expression of the calcium-sensing receptor (CaSR) was nearly
      doubled in GPR4-/- kidneys, in the absence of apparent disturbances of Ca(2+)
      homeostasis. In summary, the expression and activity of the key transport
      proteins in GPR4-/- mice are consistent with spontaneous metabolic acidosis, but
      the adaptive response to a superimposed exogenous acid load is blunted and might
      be partially compensated for by CaSR.

PMID- 25972513
TI  - Pendrin gene ablation alters ENaC subcellular distribution and open probability.
AB  - The present study explored whether the intercalated cell Cl(-)/HCO3(-) exchanger
      pendrin modulates epithelial Na(+) channel (ENaC) function by changing channel
      open probability and/or channel density. To do so, we measured ENaC subunit
      subcellular distribution by immunohistochemistry, single channel recordings in
      split open cortical collecting ducts (CCDs), as well as transepithelial voltage
      and Na(+) absorption in CCDs from aldosterone-treated wild-type and pendrin-null
      mice. Because pendrin gene ablation reduced 70-kDa more than 85-kDa gamma-ENaC
      band density, we asked if pendrin gene ablation interferes with ENaC cleavage. We
      observed that ENaC-cleaving protease application (trypsin) increased the lumen
      negative transepithelial voltage in pendrin-null mice but not in wild-type mice,
      which raised the possibility that pendrin gene ablation blunts ENaC cleavage,
      thereby reducing open probability. In mice harboring wild-type ENaC, pendrin gene
      ablation reduced ENaC-mediated Na(+) absorption by reducing channel open
      probability as well as by reducing channel density through changes in subunit
      total protein abundance and subcellular distribution. Further experiments used
      mice with blunted ENaC endocytosis and degradation (Liddle's syndrome) to explore
      the significance of pendrin-dependent changes in ENaC open probability. In mouse
      models of Liddle's syndrome, pendrin gene ablation did not change ENaC subunit
      total protein abundance, subcellular distribution, or channel density, but
      markedly reduced channel open probability. We conclude that in mice harboring
      wild-type ENaC, pendrin modulates ENaC function through changes in subunit
      abundance, subcellular distribution, and channel open probability. In a mouse
      model of Liddle's syndrome, however, pendrin gene ablation reduces channel
      activity mainly through changes in open probability.

PMID- 25972514
TI  - Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area
      At-Risk.
AB  - RATIONALE: After acute myocardial infarction (MI), delineating the area-at-risk
      (AAR) is crucial for measuring how much, if any, ischemic myocardium has been
      salvaged. T2-weighted MRI is promoted as an excellent method to delineate the
      AAR. However, the evidence supporting the validity of this method to measure the
      AAR is indirect, and it has never been validated with direct anatomic
      measurements. OBJECTIVE: To determine whether T2-weighted MRI delineates the AAR.
      METHODS AND RESULTS: Twenty-one canines and 24 patients with acute MI were
      studied. We compared bright-blood and black-blood T2-weighted MRI with images of
      the AAR and MI by histopathology in canines and with MI by in vivo delayed
      enhancement MRI in canines and patients. Abnormal regions on MRI and pathology
      were compared by (a) quantitative measurement of the transmural-extent of the
      abnormality and (b) picture matching of contours. We found no relationship
      between the transmural-extent of T2-hyperintense regions and that of the AAR
      (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there
      was a strong correlation with that of infarction (bright-blood-T2: r=0.94,
      P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis
      demonstrated a fingerprint match of T2-hyperintense regions with the intricate
      contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients
      there was a close correspondence between contours of T2-hyperintense and
      infarcted regions, and the transmural-extent of these regions were highly
      correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001).
      CONCLUSION: T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI
      should not be used to measure myocardial salvage, either to inform patient
      management decisions or to evaluate novel therapies for acute MI.

PMID- 25972515
TI  - Clinical efficacy of Daikenchuto for gastrointestinal dysfunction following colon
      surgery: a randomized, double-blind, multicenter, placebo-controlled study
      (JFMC39-0902).
AB  - OBJECTIVE: This exploratory trial was performed to determine whether Daikenchuto
      accelerates recovery of gastrointestinal function in patients undergoing open
      colectomy for colon cancer. METHODS: A total of 386 patients undergoing colectomy
      at 1 of the 51 clinical trial sites in Japan from January 2009 to June 2011 were
      registered for the study (JFMC39-0902). Patients received either placebo or
      Daikenchuto (15.0 g/day, t.i.d) between post-operative day 2 and post-operative
      day 8. Primary end-points included time to first bowel movement, frequency of
      bowel movement and stool form. The incidence of intestinal obstruction was
      evaluated post-operatively. The safety profile of Daikenchuto until post
      operative day 8 was also evaluated. RESULTS: The results for 336 patients
      (Daikenchuto, n = 174; placebo, n = 162) were available for statistical analysis.
      The time to first bowel movement did not differ significantly between the two
      groups. All patients reported having diarrhea or soft stools immediately after
      surgery, and the time until stool normalization (50th percentile) in the
      Daikenchuto and placebo groups was 6 days and 7 days, respectively. The placebo
      group had a significantly greater number of hard stools at post-operative day 8
      (P = 0.016), and bowel movement frequency continued to increase until post
      operative day 8 as well. In contrast, bowel movement frequency in the Daikenchuto
      group increased until post-operative day 6, however decreased from post-operative
      day 7 and was significantly lower at post-operative day 8 compared with the
      placebo group (P = 0.024). CONCLUSION: The moderate effects of Daikenchuto were
      observed ~1 week after the operation. Although Daikenchuto had an effect on
      gastrointestinal function after open surgery in patients with colon cancer, this
      study did not show its clinical benefits adequately.

PMID- 25972516
TI  - Racial/Ethnic Disparities in the Risk of Injury Related to the Frequency of Heavy
      Drinking Occasions.
AB  - AIMS: To estimate the risk of injury associated with the frequency of heavy
      drinking days overall and for black, white and Hispanic drinkers in a US sample.
      METHODS: Data are from the 2010 National Alcohol Survey and included 6506
      respondents comprising the landline sample. Analyses utilize Cox proportional
      hazards models with age as the timescale in a retrospective cohort design. Life
      course drinking is determined by age of onset and questions on heavy drinking by
      decade of life. The outcome measure is having had a serious injury at a certain
      age. Models estimate the risk of injury in relation to heavy drinking in each
      year controlling for demographics, risk taking and time varying measures of
      smoking and chronic disease. RESULTS: Results indicate that the risk of injury
      increases with the frequency of heavy drinking days to a hazard ratio of 2.14
      (1.45-3.14) for daily heavy drinkers. Risks for white respondents were similar to
      the overall results but different risk relationships were found for black
      respondents among whom only daily heavy drinkers had increased risk of 4.09 (2.11
      7.93), and for Hispanic respondents where elevated risk was seen among yearly
      heavy drinkers 2.71 (1.29-5.68), with a similar risk estimate for monthly heavy
      drinkers but lower and non-significant risks found for more frequent heavy
      drinking categories. CONCLUSIONS: Different risk relationships were found across
      race/ethnicity groups suggesting elevated risk with less frequent heavy drinking
      among Hispanic respondents and very high risk from daily heavy drinking among
      black respondents.

PMID- 25972517
TI  - A Systematic Comparison of 18F-C-SNAT to Established Radiotracer Imaging Agents
      for the Detection of Tumor Response to Treatment.
AB  - PURPOSE: An early readout of tumor response to therapy through measurement of
      drug or radiation-induced cell death may provide important prognostic indications
      and improved patient management. It has been shown that the uptake of (18)F-C
      SNAT can be used to detect early response to therapy in tumors by positron
      emission tomography (PET) via a mechanism of caspase-3-triggered nanoaggregation.
      EXPERIMENTAL DESIGN: Here, we compared the preclinical utility of (18)F-C-SNAT
      for the detection of drug-induced cell death to clinically evaluated
      radiotracers, (18)F-FDG, (99m)Tc-Annexin V, and (18)F-ML-10 in tumor cells in
      culture, and in tumor-bearing mice in vivo. RESULTS: In drug-treated lymphoma
      cells, (18)F-FDG, (99m)Tc-Annexin V, and (18)F-C-SNAT cell-associated
      radioactivity correlated well to levels of cell death (R(2) > 0.8; P < 0.001),
      with no correlation measured for (18)F-ML-10 (R(2) = 0.05; P > 0.05). A similar
      pattern of response was observed in two human NSCLC cell lines following
      carboplatin treatment. EL-4 tumor uptake of (99m)Tc-Annexin V and (18)F-C-SNAT
      were increased 1.4- and 2.1-fold, respectively, in drug-treated versus naive
      control animals (P < 0.05), although (99m)Tc-Annexin V binding did not correlate
      to ex vivo TUNEL staining of tissue sections. A differential response was not
      observed with either (18)F-FDG or (18)F-ML-10. CONCLUSIONS: We have demonstrated
      here that (18)F-C-SNAT can sensitively detect drug-induced cell death in murine
      lymphoma and human NSCLC. Despite favorable image contrast obtained with (18)F-C
      SNAT, the development of next-generation derivatives, using the same novel and
      promising uptake mechanism, but displaying improved biodistribution profiles, are
      warranted for maximum clinical utility.

PMID- 25972518
TI  - Backs against the wall: novel and existing strategies used during the 2014-2015
      Ebola virus outbreak.
AB  - The 2014-2015 outbreak of Ebola virus (EBOV), originating from Guinea, is now
      responsible for the infection of >20,000 people in 9 countries. Whereas past
      filovirus outbreaks in sub-Saharan Africa have been rapidly brought under control
      with comparably few cases, this outbreak has been particularly resistant to
      containment efforts. Both the general population and primary health care workers
      have been affected by this outbreak, with hundreds of doctors and nurses being
      infected in the line of duty. In the absence of approved therapeutics, several
      caregivers have turned to investigational new drugs as well as experimental
      therapies in an effort to save lives. This review aims to summarize the
      candidates currently under consideration for postexposure use in infected
      patients during the largest EBOV outbreak in history. 

PMID- 25972519
TI  - Disease-modifying antirheumatic drug-free sustained remission in rheumatoid
      arthritis: an increasingly achievable outcome with subsidence of disease
      symptoms.
AB  - OBJECTIVE: Disease-modifying antirheumatic drug (DMARD)-free sustained remission,
      the sustained absence of synovitis after cessation of DMARD therapy, is a
      relevant long-term outcome of rheumatoid arthritis (RA) if (1) its occurrence is
      promoted by treatment and (2) this status reflects resolution of symptoms and
      disability. This study investigated both items. METHODS: 1007 patients with RA
      diagnosed between 1993 and 2011, included in the Leiden Early Arthritis Clinic,
      were studied on achieving DMARD-free sustained remission. Patients included in
      1993-1995 were initially treated with non-steroidal anti-inflammatory drugs, in
      1996-1998 mild DMARDs were started early, from 1999 onwards methotrexate was
      initiated promptly and from 2005 onwards disease activity score (DAS)-steered
      treatment was common. Remission rates were compared using Kaplan-Meier curves and
      Cox proportional regression. RESULTS: In total, 155 patients achieved DMARD-free
      sustained remission. Specific treatment strategies were significantly associated
      with achieving remission (p<0.001). Cox regression adjusted for anticitrullinated
      protein antibody/rheumatoid factor, swollen joint count, erythrocyte
      sedimentation rate, C-reactive protein revealed HRs for DMARD-free sustained
      remission of 1.13 (95% CI 0.48 to 2.64) in patients diagnosed in 1996-1998, 2.39
      (1.07 to 5.32) in patients treated with early methotrexate (inclusion 1999-2004)
      and 3.72 (1.60 to 8.62) in those treated early with methotrexate and DAS-steered
      therapy (inclusion 2005-2011). At the time of remission, the Health Assessment
      Questionnaire was at the level of the general population (median 0.13, IQR 0
      0.63). Also, patient-rated visual analogue scale (VAS) morning stiffness,
      fatigue, pain and disease activity were low (median (IQR) mm, 14 (2-27), 10 (0
      47), 6 (0-20), 7 (0-20), respectively). CONCLUSIONS: More intensive treatment
      strategies increased the chance for DMARD-free sustained remission, indicating
      that RA chronicity can be influenced. Patients with RA achieving DMARD-free
      sustained remission have a normalised functional status.

PMID- 25972520
TI  - Moving the mountain: analysis of the effort required to transform comparative
      anatomy into computable anatomy.
AB  - The diverse phenotypes of living organisms have been described for centuries, and
      though they may be digitized, they are not readily available in a computable
      form. Using over 100 morphological studies, the Phenoscape project has
      demonstrated that by annotating characters with community ontology terms, links
      between novel species anatomy and the genes that may underlie them can be made.
      But given the enormity of the legacy literature, how can this largely unexploited
      wealth of descriptive data be rendered amenable to large-scale computation? To
      identify the bottlenecks, we quantified the time involved in the major aspects of
      phenotype curation as we annotated characters from the vertebrate phylogenetic
      systematics literature. This involves attaching fully computable logical
      expressions consisting of ontology terms to the descriptions in character-by
      taxon matrices. The workflow consists of: (i) data preparation, (ii) phenotype
      annotation, (iii) ontology development and (iv) curation team discussions and
      software development feedback. Our results showed that the completion of this
      work required two person-years by a team of two post-docs, a lead data curator,
      and students. Manual data preparation required close to 13% of the effort. This
      part in particular could be reduced substantially with better community data
      practices, such as depositing fully populated matrices in public repositories.
      Phenotype annotation required ~40% of the effort. We are working to make this
      more efficient with Natural Language Processing tools. Ontology development
      (40%), however, remains a highly manual task requiring domain (anatomical)
      expertise and use of specialized software. The large overhead required for data
      preparation and ontology development contributed to a low annotation rate of
      approximately two characters per hour, compared with 14 characters per hour when
      activity was restricted to character annotation. Unlocking the potential of the
      vast stores of morphological descriptions requires better tools for efficiently
      processing natural language, and better community practices towards a born
      digital morphology. Database URL: http://kb.phenoscape.org

PMID- 25972521
TI  - AtmiRNET: a web-based resource for reconstructing regulatory networks of
      Arabidopsis microRNAs.
AB  - Compared with animal microRNAs (miRNAs), our limited knowledge of how miRNAs
      involve in significant biological processes in plants is still unclear. AtmiRNET
      is a novel resource geared toward plant scientists for reconstructing regulatory
      networks of Arabidopsis miRNAs. By means of highlighted miRNA studies in target
      recognition, functional enrichment of target genes, promoter identification and
      detection of cis- and trans-elements, AtmiRNET allows users to explore mechanisms
      of transcriptional regulation and miRNA functions in Arabidopsis thaliana, which
      are rarely investigated so far. High-throughput next-generation sequencing
      datasets from transcriptional start sites (TSSs)-relevant experiments as well as
      five core promoter elements were collected to establish the support vector
      machine-based prediction model for Arabidopsis miRNA TSSs. Then, high-confidence
      transcription factors participate in transcriptional regulation of Arabidopsis
      miRNAs are provided based on statistical approach. Furthermore, both
      experimentally verified and putative miRNA-target interactions, whose validity
      was supported by the correlations between the expression levels of miRNAs and
      their targets, are elucidated for functional enrichment analysis. The inferred
      regulatory networks give users an intuitive insight into the pivotal roles of
      Arabidopsis miRNAs through the crosstalk between miRNA transcriptional regulation
      (upstream) and miRNA-mediate (downstream) gene circuits. The valuable information
      that is visually oriented in AtmiRNET recruits the scant understanding of plant
      miRNAs and will be useful (e.g. ABA-miR167c-auxin signaling pathway) for further
      research. Database URL: http://AtmiRNET.itps.ncku.edu.tw/

PMID- 25972522
TI  - Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in
      Female ApoE Knockout Mice.
AB  - BACKGROUND: Dietary silicon has been positively linked with vascular health and
      protection against atherosclerotic plaque formation, but the mechanism of action
      is unclear. OBJECTIVES: We investigated the effect of dietary silicon on 1) serum
      and aorta silicon concentrations, 2) the development of aortic lesions and serum
      lipid concentrations, and 3) the structural and biomechanic properties of the
      aorta. METHODS: Two studies, of the same design, were conducted to address the
      above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and
      therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15
      mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol)
      but with differing concentrations of dietary silicon, namely: silicon-deprived (
      Si; <3-MUg silicon/g feed), silicon-replete in feed (+Si-feed; 100-MUg silicon/g
      feed), and silicon-replete in drinking water (+Si-water; 115-MUg silicon/mL) for
      15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed)
      or monomethylsilanetriol (drinking water). RESULTS: The serum silicon
      concentration in the -Si group was significantly lower than in the +Si-feed (by
      up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The
      aorta silicon concentration was also lower in the -Si group than in the +Si-feed
      group (by 65%; P = 0.025), but not compared with the +Si-water group. There were
      no differences in serum and aorta silicon concentrations between the silicon
      replete groups. Body weights, tissue wet weights at necropsy, and structural,
      biomechanic, and morphologic properties of the aorta were not affected by dietary
      silicon; nor were the development of fatty lesions and serum lipid
      concentrations. CONCLUSIONS: These findings suggest that dietary silicon has no
      effect on atherosclerosis development and vascular health in the apoE mouse model
      of diet-induced atherosclerosis, contrary to the reported findings in the
      cholesterol-fed rabbit model.

PMID- 25972523
TI  - Midupper Arm Circumference Outperforms Weight-Based Measures of Nutritional
      Status in Children with Diarrhea.
AB  - BACKGROUND: Undernutrition contributes to 45% of all deaths in children <5 y of
      age worldwide, with a large proportion of those deaths caused by diarrhea.
      However, no validated tools exist for assessing undernutrition in children with
      diarrhea and possible dehydration. OBJECTIVE: This study assessed the validity of
      different measures of undernutrition in children with diarrhea. METHODS: A
      prospective cohort study was conducted at an urban hospital in Bangladesh.
      Children <60 mo of age presenting to the hospital rehydration unit with acute
      diarrhea were eligible for enrollment. Study staff randomly selected 1196
      children for screening, of which 1025 were eligible, 850 were enrolled, and 721
      had complete data for analysis. Anthropometric measurements, including weight-for
      age z score (WAZ), weight-for-length z score (WLZ), midupper arm circumference
      (MUAC), and midupper arm circumference z score (MUACZ), were calculated pre- and
      posthydration in all patients. Measurements were evaluated for their ability to
      correctly identify undernutrition in children with varying degrees of
      dehydration. RESULTS: Of the 721 patients with full data for analysis, the median
      percent dehydration was 4%. Of the 4 measures evaluated, MUAC and MUACZ
      demonstrated 92-94% agreement pre- and posthydration compared with 69-76% for WAZ
      and WLZ. Although each 1% change in hydration status was found to change weight
      for-age by 0.0895 z scores and weight-for-length by 0.1304 z scores, MUAC and
      MUACZ were not significantly affected by dehydration status. Weight-based
      measures misclassified 12% of children with severe underweight and 14% with
      severe acute malnutrition (SAM) compared with only 1-2% for MUAC and MUACZ.
      CONCLUSIONS: MUAC and MUACZ were the most accurate predictors of undernutrition
      in children with diarrhea. WAZ and WLZ were significantly affected by dehydration
      status, leading to the misdiagnosis of many patients on arrival with severe
      underweight and SAM. This trial was registered at clinicaltrials.gov as
      NCT02007733.

PMID- 25972524
TI  - Dietary Plant Sterol Esters Must Be Hydrolyzed to Reduce Intestinal Cholesterol
      Absorption in Hamsters.
AB  - BACKGROUND: Elevated concentrations of LDL cholesterol are associated with the
      development of atherosclerosis and therefore are considered an important target
      for intervention to prevent cardiovascular diseases. The inhibition of
      cholesterol absorption in the small intestine is an attractive approach to
      lowering plasma cholesterol, one that is addressed by drug therapy as well as
      dietary supplementation with plant sterols and plant sterol esters (PSEs).
      OBJECTIVE: This study was conducted to test the hypothesis that the cholesterol
      lowering effects of PSE require hydrolysis to free sterols (FSs). METHODS: Male
      Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing
      0.12% cholesterol and 8% coconut oil) to which one of the following was added: no
      PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters
      (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic
      nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively
      created a spectrum of PSE hydrolysis across which cholesterol metabolism could be
      compared. Metabolic measurements included cholesterol absorption, plasma and
      liver lipid concentration, and fecal neutral sterol and bile acid excretion.
      RESULTS: The STs and the PEs and SEs were poorly hydrolyzed (1.69-4.12%). In
      contrast, OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively
      correlated with cholesterol absorption (r = -0.85; P < 0.0001) and positively
      correlated with fecal cholesterol excretion (r = 0.92; P < 0.0001), suggesting
      that PSE hydrolysis plays a central role in the cholesterol-lowering properties
      of PSE. CONCLUSIONS: Our data on hamsters suggest that PSE hydrolysis and the
      presence of FSs is necessary to induce an optimum cholesterol-lowering effect and
      that poorly hydrolyzed PSEs may lower cholesterol through an alternative
      mechanism than that of competition with cholesterol for micelle incorporation.

PMID- 25972526
TI  - Use of Folate-Based and Other Fortification Scenarios Illustrates Different
      Shifts for Tails of the Distribution of Serum 25-Hydroxyvitamin D Concentrations.
AB  - BACKGROUND: The purpose of food fortification is to affect those at the lower end
      of the distribution curve for nutrient status while avoiding unintended
      consequences for those at the high end of the distribution. Vitamin D presents
      challenges in this regard. OBJECTIVES: We used scenarios to model changes in
      concentrations of serum 25-hydroxyvitamin D [25(OH)D] based on increases made
      because of assumptions about fortification. We then examined the outcomes for
      balance between improving serum 25(OH)D status for those at risk of inadequacy
      while avoiding high concentrations for those not at risk. METHODS: Data from
      NHANES 2001-2006 served as baseline serum 25(OH)D concentrations and were used to
      model shifts in serum 25(OH)D distribution after application of 3 fortification
      scenarios, including conceptual scenarios and an experiential predictive scenario
      we developed with the use of statistical modeling of changes in NHANES serum
      folate concentrations between prefortification and postfortification time
      periods. RESULTS: All scenarios suggested the possibility of increasing serum
      25(OH)D above 125 nmol/L among the proportion of the population at the high end
      of baseline serum 25(OH)D distribution. The scenario based on serum folate change
      struck a middle ground between the 2 conceptual scenarios. It predicted a
      prevalence of 11% <40 nmol/L serum 25(OH)D compared with 17% currently (study
      baseline), and 8% prevalence of serum 25(OH)D >125 nmol/L compared with <1%
      currently (study baseline). It also confirmed that fortification affects those at
      the low end of the status distribution curve differently from those at the high
      end. CONCLUSIONS: Nutrient inadequacy of the type demonstrated by vitamin D--in
      which the risk is not universal--requires a thorough exploration of the
      unintended consequences of the overall shift in the distribution of serum 25(OH)D
      if efforts are made to use fortification to increase the status of persons at
      risk of deficiency. Fortification is at best a blunt instrument that must be
      implemented with caution. Moreover, fortification must be preceded by more
      research to elucidate the dose-response relation between intake and changes in
      serum 25(OH)D.

PMID- 25972525
TI  - Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat
      Diet.
AB  - BACKGROUND: Relations of the 25 mammalian selenoprotein genes with obesity and
      the associated inflammation remain unclear. OBJECTIVE: This study explored
      impacts of high-fat diet-induced obesity on inflammation and expressions of
      selenoprotein and obesity-related genes in 10 tissues of pigs. METHODS: Plasma
      and 10 tissues were collected from pigs (n = 10) fed a corn-soy-based control
      diet or that diet containing 3-7% lard from weanling to finishing (180 d). Plasma
      concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA
      abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were
      compared between the pigs fed the control and high-fat diets. Stepwise regression
      was applied to analyze correlations among all these measures, including the
      previously reported body physical and plasma biochemical variables. RESULTS: The
      high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor
      alpha, interleukin-6, leptin, and leptin receptor by 29-42% and affected (P <
      0.05-0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3
      patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in
      6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no
      effect on 5 genes in any tissue. Body weights and plasma triglyceride
      concentrations of pigs showed the strongest regressions to tissue mRNA abundances
      of selenoprotein and obesity-related genes. Among the selenoprotein genes,
      selenoprotein V and I were ranked as the strongest independent variables for the
      regression of phenotypic and plasma measures. Meanwhile, agouti signaling
      protein, adiponectin, and resistin genes represented the strongest independent
      variables of the obesity-related genes for the regression of tissue selenoprotein
      mRNA. CONCLUSIONS: The high-fat diet induced inflammation in pigs and affected
      their gene expression of selenoproteins associated with thioredoxin and
      oxidoreductase systems, local tissue thyroid hormone activity, endoplasmic
      reticulum protein degradation, and phosphorylation of lipids. This porcine model
      may be used to study interactive mechanisms between excess fat intake and
      selenoprotein function.

PMID- 25972527
TI  - Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some
      Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive
      Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial.
AB  - BACKGROUND: Consumption of flavonoid-rich foods such as cocoa and tea may reduce
      cardiovascular disease risk. The flavonoids epicatechin (in cocoa and tea) and
      quercetin (in tea) probably play a role by reducing endothelial dysfunction and
      inflammation, 2 main determinants of atherosclerosis. OBJECTIVE: We studied the
      effects of supplementation of pure epicatechin and quercetin on biomarkers of
      endothelial dysfunction and inflammation. METHODS: Thirty-seven apparently
      healthy (pre)hypertensive men and women (40-80 y) participated in a randomized,
      double-blind, placebo-controlled crossover trial. Participants ingested (-)
      epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for
      a period of 4 wk, in random order. Plasma biomarkers of endothelial dysfunction
      and inflammation were measured at the start and end of each 4-wk intervention
      period. The differences in changes over time between the intervention and placebo
      periods (Deltaintervention - Deltaplacebo) were calculated and tested with a
      linear mixed model for repeated measures. RESULTS: Epicatechin changed
      Deltaepicatechin - Deltaplacebo for soluble endothelial selectin (sE-selectin) by
      -7.7 ng/mL (95% CI: -14.5, -0.83; P = 0.03) but did not significantly change this
      difference (-0.30; 95% CI: -0.61, 0.01; P = 0.06) for the z score for endothelial
      dysfunction. Quercetin changed Deltaquercetin - Deltaplacebo for sE-selectin by 
      7.4 ng/mL (95% CI: -14.3, -0.56; P = 0.03), that for IL-1beta by -0.23 pg/mL (95%
      CI: -0.40, -0.06; P = 0.009), and that for the z score for inflammation by -0.33
      (95% CI: -0.60, -0.05; P = 0.02). CONCLUSIONS: In (pre)hypertensive men and
      women, epicatechin may contribute to the cardioprotective effects of cocoa and
      tea through improvements in endothelial function. Quercetin may contribute to the
      cardioprotective effects of tea possibly by improving endothelial function and
      reducing inflammation. This trial was registered at clinicaltrials.gov as
      NCT01691404.

PMID- 25972529
TI  - Importance of Animals in Agricultural Sustainability and Food Security.
AB  - A conservative projection shows the world's population growing by 32% (to 9.5
      billion) by 2050 and 53% (to 11 billion) by 2100 compared with its current level
      of 7.2 billion. Because most arable land worldwide is already in use, and water
      and energy also are limiting, increased production of food will require a
      substantial increase in efficiency. In this article, we highlight the importance
      of animals to achieving food security in terms of their valuable contributions to
      agricultural sustainability, especially in developing countries, and the high
      nutritional value of animal products in the diet. 

PMID- 25972528
TI  - Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline
      Metabolite Concentrations.
AB  - BACKGROUND: Choline deficiency during pregnancy can lead to adverse birth
      outcomes, including impaired neurodevelopment and birth defects. Genetic variants
      of choline and one-carbon metabolism may also influence birth outcomes by
      altering plasma choline concentrations. The effects of maternal ad libitum
      choline intake during pregnancy and fetal genetic variants on maternal and cord
      concentrations of choline and its metabolites are unknown. OBJECTIVES: This
      prospective study sought to assess the effect of 1) maternal dietary choline
      intake on maternal and cord plasma concentrations of choline and its metabolites,
      and 2) fetal genetic polymorphisms on cord plasma concentrations. METHODS: The
      dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16
      wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire.
      Plasma concentrations of free choline and its metabolites were measured in
      maternal samples at recruitment and delivery, and in the cord blood. Ten fetal
      genetic variants in choline and one-carbon metabolism were assessed for their
      association with cord plasma concentrations of free choline and its metabolites.
      RESULTS: Mean maternal plasma free choline, dimethylglycine, and trimethylamine N
      oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%,
      respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P <
      0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and
      TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at
      delivery, respectively (all P < 0.005). Maternal plasma concentrations of
      betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery
      were moderately strong, whereas maternal concentrations of free choline were not
      significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of
      these metabolites. Neither maternal dietary intake nor fetal genetic variants
      predicted maternal or cord plasma concentrations of choline and its metabolites.
      CONCLUSION: These data collectively indicate that maternal choline status, but
      not fetal genotype, influences cord plasma concentrations of choline metabolites.
      This trial was registered at clinicaltrials.gov as NCT02244684.

PMID- 25972530
TI  - Vitamin B-12 Deficiency in Children Is Associated with Grade Repetition and
      School Absenteeism, Independent of Folate, Iron, Zinc, or Vitamin A Status
      Biomarkers.
AB  - BACKGROUND: Micronutrients are essential to neurocognitive development; yet their
      role in educational outcomes is unclear. OBJECTIVE: We examined the associations
      of micronutrient status biomarkers with the risk of grade repetition and rates of
      school absenteeism in a cohort of school children. METHODS: We recruited 3156
      children aged 5-12 y from public schools in Bogota, Colombia. Circulating
      ferritin, hemoglobin, zinc, vitamin A, and vitamin B-12; erythrocyte folate; and
      mean corpuscular volume (MCV) were measured in blood samples obtained at the
      beginning of the year. Absenteeism was recorded weekly during the school year,
      and grade repetition was determined the next year. Risk ratios for grade
      repetition and rate ratios for absenteeism were estimated by categories of
      micronutrient status indicators with use of Poisson regression, adjusting for
      potential confounders. RESULTS: The risk of grade repetition was 4.9%, and the
      absenteeism rate was 3.8 d per child-year of observation. Vitamin B-12 deficiency
      (<148 pmol/L) was associated with an adjusted 2.36-fold greater risk of grade
      repetition (95% CI: 1.03, 5.41; P = 0.04) compared with plasma concentrations
      >=148 pmol/L. Other micronutrients were not related to grade repetition. Vitamin
      B-12 deficiency was also associated with school absenteeism rates. Compared with
      children with plasma vitamin B-12 concentrations >=148 pmol/L, vitamin B-12
      deficient children had a 1.89-times higher adjusted rate (95% CI: 1.53, 2.34; P <
      0.0001). Anemia was related to a 72% higher rate (95% CI: 48%, 99%; P < 0.0001),
      whereas every 5-fL difference in MCV was associated with a 7% lower adjusted rate
      (95% CI: 4%, 10%; P < 0.0001). CONCLUSIONS: Vitamin B-12 deficiency was
      associated with risk of grade repetition and school absenteeism rates in school
      children from Bogota, Colombia. The effects of correcting vitamin B-12 deficiency
      on educational outcomes and neurocognitive development of school children need to
      be determined in intervention studies.

PMID- 25972532
TI  - Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional
      Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing
      Cardiovascular Disease.
AB  - BACKGROUND: Improving diet and lifestyle is important for prevention of
      cardiovascular disease (CVD). Observational evidence suggests that increasing
      fruit and vegetable (FV) consumption may lower CVD risk, largely through
      modulation of established risk factors, but intervention data are required to
      fully elucidate the mechanisms by which FVs exert benefits on vascular health.
      OBJECTIVE: The aim of this study was to examine the dose-response effect of FV
      intake on cardiovascular risk factors in adults at high CVD risk. METHODS: This
      was a randomized controlled parallel group study involving overweight adults
      (BMI: >27 and <=35 kg/m(2)) with a habitually low FV intake (<=160 g/d) and a
      high total risk of developing CVD (estimated >=20% over 10 y). After a 4-wk run
      in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible
      participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or
      7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for
      12 consecutive weeks. Fasting venous blood samples were collected at baseline
      (week 4) and post-intervention (week 16) for analysis of lipid fractions and high
      sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV
      intervention was determined with use of self-reported FV intake and biomarkers of
      micronutrient status. Ambulatory blood pressure and body composition were also
      measured pre- and post-intervention. RESULTS: A total of 89 participants
      completed the study and body composition remained stable throughout the
      intervention period. Despite good compliance with the intervention, no
      significant difference was found between the FV groups for change in measures of
      ambulatory blood pressure, plasma lipids, or hsCRP concentrations. CONCLUSIONS:
      There was no evidence of a dose-response effect of FV intake on conventional CVD
      risk factors measured in overweight adults at high CVD risk. This trial was
      registered at clinicaltrials.gov as NCT00874341.

PMID- 25972531
TI  - Common Variants at Putative Regulatory Sites of the Tissue Nonspecific Alkaline
      Phosphatase Gene Influence Circulating Pyridoxal 5'-Phosphate Concentration in
      Healthy Adults.
AB  - BACKGROUND: Vitamin B-6 interconversion enzymes are important for supplying
      pyridoxal 5'-phosphate (PLP), the co-enzyme form, to tissues. Variants in the
      genes for these enzymes [tissue nonspecific alkaline phosphatase (ALPL),
      pyridoxamine 5'-phosphate oxidase, pyridoxal kinase, and pyridoxal phosphatase]
      could affect enzyme function and vitamin B-6 status. OBJECTIVES: We tested
      whether single-nucleotide polymorphisms (SNPs) in these genes influence vitamin B
      6 status markers [plasma PLP, pyridoxal (PL), and 4-pyridoxic acid (PA)], and
      explored potential functional effects of the SNPs. METHODS: Study subjects were
      young, healthy adults from Ireland (n = 2345). We measured plasma PLP, PL, and PA
      with liquid chromatography-tandem mass spectrometry and genotyped 66 tag SNPs in
      the 4 genes. We tested for associations with single SNPs in candidate genes and
      also performed genome-wide association study (GWAS) and gene-based analyses.
      RESULTS: Seventeen SNPs in ALPL were associated with altered plasma PLP in
      candidate gene analyses (P < 1.89 * 10(-4)). In the GWAS, 5 additional ALPL SNPs
      were associated with altered plasma PLP (P < 5.0 * 10(-8)). Gene-based analyses
      that used the functional linear model beta-spline (P = 4.04 * 10(-15)) and
      Fourier spline (P = 5.87 * 10(-15)) methods also showed associations between ALPL
      and altered plasma PLP. No SNPs in other genes were associated with plasma PLP.
      The association of the minor CC genotype of 1 ALPL SNP, rs1256341, with reduced
      ALPL expression in the HapMap Northern European ancestry population is consistent
      with the positive association between the CC genotype and plasma PLP in our study
      (P = 0.008). No SNP was associated with altered plasma PL or PA. CONCLUSIONS: In
      healthy adults, common variants in ALPL influence plasma PLP concentration, the
      most frequently used biomarker for vitamin B-6 status. Whether these associations
      are indicative of functional changes in vitamin B-6 status requires more
      investigation.

PMID- 25972533
TI  - Molecular Mechanism for LAMP1 Recognition by Lassa Virus.
AB  - Lassa virus is a notorious human pathogen that infects many thousands of people
      each year in West Africa, causing severe viral hemorrhagic fevers and significant
      mortality. The surface glycoprotein of Lassa virus mediates receptor recognition
      through its GP1 subunit. Here we report the crystal structure of GP1 from Lassa
      virus, which is the first representative GP1 structure for Old World
      arenaviruses. We identify a unique triad of histidines that forms a binding site
      for LAMP1, a known lysosomal protein recently discovered to be a critical
      receptor for internalized Lassa virus at acidic pH. We demonstrate that mutation
      of this histidine triad, which is highly conserved among Old World arenaviruses,
      impairs LAMP1 recognition. Our biochemical and structural data further suggest
      that GP1 from Lassa virus may undergo irreversible conformational changes that
      could serve as an immunological decoy mechanism. Together with a variable region
      that we identify on the surface of GP1, those could be two distinct mechanisms
      that Lassa virus utilizes to avoid antibody-based immune response. IMPORTANCE:
      Structural data at atomic resolution for viral proteins is key for understanding
      their function at the molecular level and can facilitate novel avenues for
      combating viral infections. Here we used X-ray protein crystallography to
      decipher the crystal structure of the receptor-binding domain (GP1) from Lassa
      virus. This is a pathogenic virus that causes significant illness and mortality
      in West Africa. This structure reveals the overall architecture of GP1 domains
      from the group of viruses known as the Old World arenaviruses. Using this
      structural information, we elucidated the mechanisms for pH switch and binding of
      Lassa virus to LAMP1, a recently identified host receptor that is critical for
      successful infection. Lastly, our structural analysis suggests two novel immune
      evasion mechanisms that Lassa virus may utilize to escape antibody-based immune
      response.

PMID- 25972534
TI  - HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell
      Activation via CD4-Dependent Mechanisms.
AB  - Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in
      response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are
      rapidly activated during HIV-1 infection and are implicated in reducing the early
      viral load, as well as contributing to HIV-1-induced pathogenesis. However, most
      cell-free HIV-1 isolates are inefficient in activating human pDCs, and the
      mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly
      defined. In this study, we report that two genetically similar HIV-1 variants
      (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to
      produce alpha interferon (IFN-alpha). The highly pathogenic R3A efficiently
      activated pDCs to induce robust IFN-alpha production, while the less pathogenic
      R3B did not. The viral determinant for efficient pDC activation was mapped to the
      V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity.
      Furthermore, we showed that the Nef protein was also required for the activation
      of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated
      that Nef domains involved in CD4 downregulation were necessary for R3A to
      activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i)
      the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity,
      which is involved in CD4 downregulation. Our findings provide new insights into
      the mechanism by which HIV-1 induces IFN-alpha in pDCs, which contributes to
      pathogenesis. IMPORTANCE: Plasmacytoid dendritic cells (pDCs) are the major type
      I interferon (IFN-I)-producing cells, and IFN-I actually contributes to
      pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the
      roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the
      highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-alpha
      production, while most HIV-1 isolates are inefficient in activating pDCs. We have
      discovered that R3A-induced pDC activation depends on (i) the high affinity of
      R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in
      CD4 downregulation. Our findings thus provide new insights into the mechanism by
      which HIV-1 induces IFN-alpha in pDCs and contributes to HIV-1 pathogenesis.
      These novel findings will be of great interest to those working on the roles of
      IFN and pDCs in HIV-1 pathogenesis in general and on the interaction of HIV-1
      with pDCs in particular.

PMID- 25972535
TI  - Vinexin beta Interacts with Hepatitis C Virus NS5A, Modulating Its
      Hyperphosphorylation To Regulate Viral Propagation.
AB  - Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is essential for HCV
      genome replication and virion production and is involved in the regulation of
      multiple host signaling pathways. As a proline-rich protein, NS5A is capable of
      interacting with various host proteins containing Src homology 3 (SH3) domains.
      Previous studies have suggested that vinexin, a member of the sorbin homology
      (SoHo) adaptor family, might be a potential binding partner of NS5A by yeast two
      hybrid screening. However, firm evidence for this interaction is lacking, and the
      significance of vinexin in the HCV life cycle remains unclear. In this study, we
      demonstrated that endogenously and exogenously expressed vinexin beta
      coimmunoprecipitated with NS5A derived from different HCV genotypes. Two
      residues, tryptophan (W307) and tyrosine (Y325), in the third SH3 domain of
      vinexin beta and conserved Pro-X-X-Pro-X-Arg motifs at the C terminus of NS5A
      were indispensable for the vinexin-NS5A interaction. Furthermore, downregulation
      of endogenous vinexin beta significantly suppressed NS5A hyperphosphorylation and
      decreased HCV replication, which could be rescued by expressing a vinexin beta
      short hairpin RNA-resistant mutant. We also found that vinexin beta modulated the
      hyperphosphorylation of NS5A in a casein kinase 1alpha-dependent on manner. Taken
      together, our findings suggest that vinexin beta modulates NS5A phosphorylation
      via its interaction with NS5A, thereby regulating HCV replication, implicating
      vinexin beta in the viral life cycle. IMPORTANCE: Hepatitis C virus (HCV)
      nonstructural protein NS5A is a phosphoprotein, and its phosphorylation states
      are usually modulated by host kinases and other viral nonstructural elements.
      Additionally, cellular factors containing Src homology 3 (SH3) domains have been
      reported to interact with proline-rich regions of NS5A. However, it is unclear
      whether there are any relationships between NS5A phosphorylation and the NS5A-SH3
      interaction, and little is known about the significance of this interaction in
      the HCV life cycle. In this work, we demonstrate that vinexin beta modulates NS5A
      hyperphosphorylation through the NS5A-vinexin beta interaction.
      Hyperphosphorylated NS5A induced by vinexin beta is casein kinase 1alpha
      dependent and is also crucial for HCV propagation. Overall, our findings not only
      elucidate the relationships between NS5A phosphorylation and the NS5A-SH3
      interaction but also shed new mechanistic insight on Flaviviridae NS5A (NS5)
      phosphorylation. We believe that our results may afford the potential to offer an
      antiviral therapeutic strategy.

PMID- 25972536
TI  - Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene
      Expression in Human Dendritic Cells.
AB  - Ebola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune
      response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which
      trigger the adaptive response, do not mature despite EBOV infection. We recently
      demonstrated that DC maturation is unblocked by disabling the innate response
      antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and
      K142A, respectively. Here we analyzed the effects of VP35 and VP24 with the IRADs
      disabled on global gene expression in human DC. Human monocyte-derived DC were
      infected by wild-type (wt) EBOV or EBOVs carrying the mutation in VP35
      (EBOV/VP35m), VP24 (EBOV/VP24m), or both (EBOV/VP35m/VP24m). Global gene
      expression at 8 and 24 h was analyzed by deep sequencing, and the expression of
      interferon (IFN) subtypes up to 5 days postinfection was analyzed by quantitative
      reverse transcription-PCR (qRT-PCR). wt EBOV induced a weak global gene
      expression response, including markers of DC maturation, cytokines, chemokines,
      chemokine receptors, and multiple IFNs. The VP35 mutation unblocked the
      expression, resulting in a dramatic increase in expression of these transcripts
      at 8 and 24 h. Surprisingly, DC infected with EBOV/VP24m expressed lower levels
      of many of these transcripts at 8 h after infection, compared to wt EBOV. In
      contrast, at 24 h, expression of the transcripts increased in DC infected with
      any of the three mutants, compared to wt EBOV. Moreover, sets of genes affected
      by the two mutations only partially overlapped. Pathway analysis demonstrated
      that the VP35 mutation unblocked pathways involved in antigen processing and
      presentation and IFN signaling. These data suggest that EBOV IRADs have profound
      effects on the host adaptive immune response through massive transcriptional
      downregulation of DC. IMPORTANCE: This study shows that infection of DC with
      EBOV, but not its mutant forms with the VP35 IRAD and/or VP24 IRAD disabled,
      causes a global block in expression of host genes. The temporal effects of
      mutations disrupting the two IRADs differ, and the lists of affected genes only
      partially overlap such that VP35 and VP24 IRADs each have profound effects on
      antigen presentation by exposed DC. The global modulation of DC gene expression
      and the resulting lack of their maturation represent a major mechanism by which
      EBOV disables the T cell response and suggests that these suppressive pathways
      are a therapeutic target that may unleash the T cell responses during EBOV
      infection.

PMID- 25972537
TI  - Hepatitis B Virus-Infected HepG2hNTCP Cells Serve as a Novel Immunological Tool
      To Analyze the Antiviral Efficacy of CD8+ T Cells In Vitro.
AB  - CD8(+) T cells are the main effector lymphocytes in the control of hepatitis B
      virus (HBV) infection. However, limitations of model systems, such as low
      infection rates, restrict mechanistic studies of HBV-specific CD8(+) T cells.
      Here, we established a novel immunological cell culture model based on HBV
      infected HepG2(hNTCP) cells that endogenously processed viral antigens and
      presented them to HBV-specific CD8(+) T cells. This induced cytolytic and
      noncytolytic CD8(+) T-cell effector functions and reduction of viral loads. 

PMID- 25972538
TI  - Tuberous Sclerosis Complex Protein 2-Independent Activation of mTORC1 by Human
      Cytomegalovirus pUL38.
AB  - The mammalian target of rapamycin complex 1 (mTORC1) controls cell growth and
      anabolic metabolism and is a critical host factor activated by human
      cytomegalovirus (HCMV) for successful infection. The multifunctional HCMV protein
      pUL38 previously has been reported to activate mTORC1 by binding to and
      antagonizing tuberous sclerosis complex protein 2 (TSC2) (J. N. Moorman et al.,
      Cell Host Microbe 3:253-262, 2008, http://dx.doi.org/10.1016/j.chom.2008.03.002).
      pUL38 also plays a role in blocking endoplasmic reticulum stress-induced cell
      death during HCMV infection. In this study, we showed that a mutant pUL38 lacking
      the N-terminal 24 amino acids (pHA-UL3825-331) was fully functional in
      suppressing cell death during infection. Interestingly, pHA-UL3825-331 lost the
      ability to interact with TSC2 but retained the ability to activate mTORC1,
      although to a lesser extent than full-length pHA-UL38. Recombinant virus
      expressing pHA-UL3825-331 replicated with ~10-fold less efficiency than the wild
      type virus at a low multiplicity of infection (MOI), but it grew similarly well
      at a high MOI, suggesting an MOI-dependent importance of pUL38-TSC2 interaction
      in supporting virus propagation. Site-directed mutational analysis identified a
      TQ motif at amino acid residues 23 and 24 as critical for pUL38 interaction with
      TSC2. Importantly, when expressed in isolation, the TQ/AA substitution mutant pHA
      UL38 TQ/AA was capable of activating mTORC1 just like pHA-UL3825-331. We also
      created TSC2-null U373-MG cell lines by CRISPR genome editing and showed that
      pUL38 was capable of further increasing mTORC1 activity in TSC2-null cells.
      Therefore, this study identified the residues important for pUL38-TSC2
      interaction and demonstrated that pUL38 can activate mTORC1 in both TSC2
      dependent and -independent manners. IMPORTANCE: HCMV, like other viruses, depends
      exclusively on its host cell to propagate. Therefore, it has developed methods to
      protect against host stress responses and to usurp cellular processes to complete
      its life cycle. mTORC1 is believed to be important for virus replication, and
      HCMV maintains high mTORC1 activity despite the stressful cellular environment
      associated with infection. mTORC1 inhibitors suppressed HCMV replication in vitro
      and reduced the incidence of HCMV reactivation in transplant recipients. We
      demonstrated that mTORC1 was activated by HCMV protein pUL38 in both TSC2
      dependent and TSC2-independent manners. The pUL38-independent mode of mTORC1
      activation also has been reported. These novel findings suggest the evolution of
      sophisticated approaches whereby HCMV activates mTORC1, indicating its importance
      in the biology and pathogenesis of HCMV.

PMID- 25972539
TI  - Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused
      by Distinct Arteriviruses.
AB  - Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical
      presentation and serological diagnosis, all reported SHF outbreaks were thought
      to be caused by different strains of the same virus, simian hemorrhagic fever
      virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in
      1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent
      arteriviruses. Our results indicate that multiple divergent simian arteriviruses
      can cause SHF. 

PMID- 25972540
TI  - A Single Point Mutation Creating a Furin Cleavage Site in the Spike Protein
      Renders Porcine Epidemic Diarrhea Coronavirus Trypsin Independent for Cell Entry
      and Fusion.
AB  - The emerging porcine epidemic diarrhea virus (PEDV) requires trypsin
      supplementation to activate its S protein for membrane fusion and virus
      propagation in cell culture. By substitution of a single amino acid in the S
      protein, we created a recombinant PEDV with an artificial furin protease cleavage
      site N terminal of the putative fusion peptide (PEDV-SFCS). PEDV-SFCS exhibited
      trypsin-independent cell-cell fusion and was able to replicate in culture cells
      independently of trypsin, though to low titer.

PMID- 25972541
TI  - Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in
      the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on
      RNA-1-Like Hypermutations.
AB  - Defective interfering RNAs (DI-RNAs) of the viral genome can form during
      infections of negative-strand RNA viruses and outgrow full-length viral genomes,
      thereby modulating the severity and duration of infection. Here we document the
      frequent de novo generation of copy-back DI-RNAs from independent rescue events
      both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323)
      as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C
      protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10
      times more DI-RNAs than parental virus, suggesting that C enhances the
      processivity of the viral polymerase. We obtained the nucleotide sequences of 65
      individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted
      their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C
      transitions. Sequences flanking these mutation sites were characteristic of those
      favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double
      stranded RNA the C-6 deamination of adenosine to produce inosine, which is
      recognized as guanosine, a process known as A-to-I RNA editing. In individual DI
      RNAs the transitions were of the same type and occurred on both sides of the
      breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated
      DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were
      incorporated into virus particles, which reduced the infectivity of virus stocks.
      The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed
      the replication of vac2, as shown by coinfections of interferon-incompetent
      lymphatic cells with viruses expressing different fluorescent reporter proteins.
      In contrast, coinfection with a C-protein-expressing virus did not counteract the
      suppressive phenotype of DI-RNAs. IMPORTANCE: Recombinant measles viruses (MVs)
      are in clinical trials as cancer therapeutics and as vectored vaccines for HIV
      AIDS and other infectious diseases. The efficacy of MV-based vectors depends on
      their replication proficiency and immune activation capacity. Here we document
      that copy-back defective interfering RNAs (DI-RNAs) are generated by recombinant
      vaccine and wild-type MVs immediately after rescue. The MV C protein interferes
      with DI-RNA generation and may enhance the processivity of the viral polymerase.
      We frequently detected clusters of A-to-G or U-to-C transitions and noted that
      sequences flanking individual mutations contain motifs favoring recognition by
      the adenosine deaminase acting on RNA-1 (ADAR1). The consistent type of
      transitions on the DI-RNAs indicates that these are direct substrates for editing
      by ADAR1. The ADAR1-mediated biased hypermutation events are consistent with the
      protein kinase R (PKR)-ADAR1 balancing model of innate immunity activation. We
      show by coinfection that the C-defective phenotype is dominant.

PMID- 25972542
TI  - Posttranslational Modifications of Baculovirus Protamine-Like Protein P6.9 and
      the Significance of Its Hyperphosphorylation for Viral Very Late Gene
      Hyperexpression.
AB  - Many viruses utilize viral or cellular chromatin machinery for efficient
      infection. Baculoviruses encode a conserved protamine-like protein, P6.9. This
      protein plays essential roles in various viral physiological processes during
      infection. However, the mechanism by which P6.9 regulates transcription remains
      unknown. In this study, 7 phosphorylated species of P6.9 were resolved in Sf9
      cells infected with the baculovirus type species Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV). Mass spectrometry identified 22 phosphorylation
      and 10 methylation sites but no acetylation sites in P6.9. Immunofluorescence
      demonstrated that the P6.9 and virus-encoded serine/threonine kinase PK1
      exhibited similar distribution patterns in infected cells, and
      coimmunoprecipitation confirmed the interaction between them. Upon pk1 deletion,
      nucleocapsid assembly and polyhedron formation were interrupted and the
      transcription of viral very late genes was downregulated. Interestingly, we found
      that the 3 most phosphorylated P6.9 species vanished from Sf9 cells transfected
      with the pk1 deletion mutant, suggesting that PK1 is involved in the
      hyperphosphorylation of P6.9. Mass spectrometry suggested that the
      phosphorylation of the 7 Ser/Thr and 5 Arg residues in P6.9 was PK1 dependent.
      Replacement of the 7 Ser/Thr residues with Ala resulted in a P6.9 phosphorylation
      pattern similar to that of the pk1 deletion mutant. Importantly, the decreases in
      the transcription level of viral very late genes and viral infectivity were
      consistent. Our findings reveal that P6.9 hyperphosphorylation is a precondition
      for the maximal hyperexpression of baculovirus very late genes and provide the
      first experimental insights into the function of the baculovirus protamine-like
      protein and the related protein kinase in epigenetics. IMPORTANCE: Diverse
      posttranslational modifications (PTMs) of histones constitute a code that creates
      binding platforms that recruit transcription factors to regulate gene expression.
      Many viruses also utilize host- or virus-induced chromatin machinery to promote
      efficient infections. Baculoviruses encode a protamine-like protein, P6.9, which
      is required for a variety of processes in the infection cycle. Currently, P6.9's
      PTM sites and its regulating factors remain unknown. Here, we found that P6.9
      could be categorized as unphosphorylated, hypophosphorylated, and
      hyperphosphorylated species and that a virus-encoded serine/threonine kinase,
      PK1, was essential for P6.9 hyperphosphorylation. Abundant PTM sites on P6.9 were
      identified, among which 7 Ser/Thr phosphorylated sites were PK1 dependent.
      Mutation of these Ser/Thr sites reduced very late viral gene transcription and
      viral infectivity, indicating that the PK1-mediated P6.9 hyperphosphorylation
      contributes to viral proliferation. These data suggest that a code exists in the
      sophisticated PTM of viral protamine-like proteins and participates in viral gene
      transcription.

PMID- 25972543
TI  - High-throughput analysis of human cytomegalovirus genome diversity highlights the
      widespread occurrence of gene-disrupting mutations and pervasive recombination.
AB  - : Human cytomegalovirus is a widespread pathogen of major medical importance. It
      causes significant morbidity and mortality in the immunocompromised and
      congenital infections can result in severe disabilities or stillbirth.
      Development of a vaccine is prioritized, but no candidate is close to release.
      Although correlations of viral genetic variability with pathogenicity are
      suspected, knowledge about strain diversity of the 235kb genome is still limited.
      In this study, 96 full-length human cytomegalovirus genomes from clinical
      isolates were characterized, quadrupling the available information for full
      genome analysis. These data provide the first high-resolution map of human
      cytomegalovirus interhost diversity and evolution. We show that cytomegalovirus
      is significantly more divergent than all other human herpesviruses and highlight
      hotspots of diversity in the genome. Importantly, 75% of strains are not
      genetically intact, but contain disruptive mutations in a diverse set of 26
      genes, including immunomodulative genes UL40 and UL111A. These mutants are
      independent from culture passaging artifacts and circulate in natural
      populations. Pervasive recombination, which is linked to the widespread
      occurrence of multiple infections, was found throughout the genome. Recombination
      density was significantly higher than in other human herpesviruses and correlated
      with strain diversity. While the overall effects of strong purifying selection on
      virus evolution are apparent, evidence of diversifying selection was found in
      several genes encoding proteins that interact with the host immune system,
      including UL18, UL40, UL142 and UL147. These residues may present phylogenetic
      signatures of past and ongoing virus-host interactions. IMPORTANCE: Human
      cytomegalovirus has the largest genome of all viruses that infect humans.
      Currently, there is a great interest in establishing associations between genetic
      variants and strain pathogenicity of this herpesvirus. Since the number of
      publicly available full-genome sequences is limited, knowledge about strain
      diversity is highly fragmented and biased towards a small set of loci. Combined
      with our previous work, we have now contributed 101 complete genome sequences. We
      have used these data to conduct the first high-resolution analysis of interhost
      genome diversity, providing an unbiased and comprehensive overview of
      cytomegalovirus variability. These data are of major value to the development of
      novel antivirals and a vaccine and to identify potential targets for genotype
      phenotype experiments. Furthermore, they have enabled a thorough study of the
      evolutionary processes that have shaped cytomegalovirus diversity.

PMID- 25972544
TI  - Conservation of the STING-Mediated Cytosolic DNA Sensing Pathway in Zebrafish.
AB  - Zebrafish (Danio rerio) is a unique potential model animal for dissecting innate
      immune signaling. Here we demonstrate that herpes simplex virus 1 (HSV-1) could
      infect zebrafish at its different developmental stages and trigger the expression
      of type I interferons (IFNs) as well as interferon-stimulated genes (ISGs) in
      zebrafish larvae. Silencing of zSTING, but not zMAVS, markedly attenuates the DNA
      virus-induced antiviral responses. Notably, a conserved serine residue (S373) is
      essential for the action of zSTING. Unexpectedly, zebrafish cyclic GMP-AMP
      synthase (cGAS) is dispensable for the STING signaling, whereas zDHX9 and zDDX41
      are potential sensors for HSV-1 infection in vivo. Taken together, this proof-of
      concept study establishes the zebrafish larva as a feasible model for
      investigating the cytosolic DNA sensing mechanism, shedding light on the
      conservation of the STING antiviral signaling pathway. IMPORTANCE: The zebrafish
      larva provides technical advantages for understanding host-pathogen interactions.
      In this study, we established the zebrafish larva as a useful model for studying
      HSV-1 infection. HSV-1 infection triggers strong type I interferon production,
      which depends on STING expression. In addition, STING-mediated antiviral
      signaling is conserved in zebrafish. Interestingly, zDHX9 and zDDX41 are
      indispensable for detecting HSV-1, while cGAS is dispensable. This proof-of
      concept study indicates that the zebrafish represents an amenable model for the
      investigation of cytosolic DNA sensing mechanisms.

PMID- 25972546
TI  - Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male
      Survival in Models of Prion Disease.
AB  - Prion diseases are fatal neurodegenerative disorders associated with the
      conversion of cellular prion protein (PrPC) into its aberrant infectious form
      (PrPSc). There is no treatment available for these diseases. The bile acids
      tauroursodeoxycholic acid(TUDCA) and ursodeoxycholic acid (UDCA) have been
      recently shown to be neuroprotective in other protein misfolding disease models,
      including Parkinson's, Huntington's and Alzheimer's diseases, and also in humans
      with amyotrophic lateral sclerosis.Here, we studied the therapeutic efficacy of
      these compounds in prion disease. We demonstrated that TUDCA and UDCA
      substantially reduced PrP conversion in cell-free aggregation assays, as well as
      in chronically and acutely infected cell cultures. This effect was mediated
      through reduction of PrPSc seeding ability, rather than an effect on PrPC. We
      also demonstrated the ability of TUDCA and UDCA to reduce neuronal loss in prion
      infected cerebellar slice cultures. UDCA treatment reduced astrocytosis and
      prolonged survival in RML prion-infected mice. Interestingly, these effects were
      limited to the males, implying a gender-specific difference in drug metabolism.
      Beyond effects on PrPSc, we found that levels of phosphorylated eIF2 were
      increased at early time points, with correlated reductions in postsynaptic
      density protein 95. As demonstrated for other neurodegenerative diseases, we now
      show that TUDCA and UDCA may have a therapeutic role in prion diseases, with
      effects on both prion conversion and neuroprotection. Our findings, together with
      the fact that these natural compounds are orally bioavailable, permeable to the
      blood-brain barrier, and U.S. Food and Drug Administration-approved for use in
      humans, make these compounds promising alternatives for the treatment of prion
      diseases. IMPORTANCE: Prion diseases are fatal neurodegenerative diseases that
      are transmissible to humans and other mammals. There are no disease-modifying
      therapies available, despite decades of research. Treatment targets have included
      inhibition of protein accumulation,clearance of toxic aggregates, and prevention
      of downstream neurodegeneration. No one target may be sufficient; rather,
      compounds which have a multimodal mechanism, acting on different targets, would
      be ideal. TUDCA and UDCA are bile acids that may fulfill this dual role. Previous
      studies have demonstrated their neuroprotective effects in several
      neurodegenerative disease models, and we now demonstrate that this effect occurs
      in prion disease, with an added mechanistic target of upstream prion seeding.
      Importantly, these are natural compounds which are orally bioavailable, permeable
      to the blood-brain barrier, and U.S.Food and Drug Administration-approved for use
      in humans with primary biliary cirrhosis. They have recently been proven
      efficacious in human amyotrophic lateral sclerosis. Therefore, these compounds
      are promising options for the treatment of prion diseases.

PMID- 25972545
TI  - Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major
      Histocompatibility Complex Class I Expression through RIG-I Induction in Airway
      Epithelial Cells.
AB  - Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract
      viral infection in infants, causing bronchiolitis and pneumonia. The host
      antiviral response to RSV acts via retinoic acid-inducible gene I (RIG-I). We
      show here that RSV infection upregulates major histocompatibility complex class I
      (MHC-I) expression through the induction of NLRC5, a NOD-like, CARD domain
      containing intracellular protein that has recently been identified as a class I
      MHC transactivator (CITA). RSV infection of A549 cells promotes upregulation of
      NLRC5 via beta interferon (IFN-beta) production, since the NLRC5-inducing
      activity in a conditioned medium from RSV-infected A549 cells was removed by
      antibody to IFN-beta, but not by antibody to IFN-gamma. RSV infection resulted in
      RIG-I upregulation and induction of NLRC5 and MHC-I. Suppression of RIG-I
      induction significantly blocked NLRC5, as well as MHC-I, upregulation and
      diminished IRF3 activation. Importantly, Vero cells deficient in interferon
      production still upregulated MHC-I following introduction of the RSV genome by
      infection or transfection, further supporting a key role for RIG-I. A model is
      therefore proposed in which the host upregulates MHC-I expression during RSV
      infection directly via the induction of RIG-I and NLRC5 expression. Since
      elevated expression of MHC-I molecules can sensitize host cells to T lymphocyte
      mediated cytotoxicity or immunopathologic damage, the results have significant
      implications for the modification of immunity in RSV disease. IMPORTANCE: Human
      respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and
      pneumonia in infants and young children worldwide. Infection early in life is
      linked to persistent wheezing and allergic asthma in later life, possibly related
      to upregulation of major histocompatibility class I (MHC-I) on the cell surface,
      which facilitates cytotoxic T cell activation and antiviral immunity. Here, we
      show that RSV infection of lung epithelial cells induces expression of RIG-I,
      resulting in induction of a class I MHC transactivator, NLRC5, and subsequent
      upregulation of MHC-I. Suppression of RIG-I induction blocked RSV-induced NLRC5
      expression and MHC-I upregulation. Increased MHC-I expression may exacerbate the
      RSV disease condition due to immunopathologic damage, linking the innate immune
      response to RSV disease.

PMID- 25972547
TI  - Two-Year Follow-Up of Macaques Developing Intermittent Control of the Human
      Immunodeficiency Virus Homolog Simian Immunodeficiency Virus SIVmac251 in the
      Chronic Phase of Infection.
AB  - Off-therapy control of viremia by HIV-infected individuals has been associated
      with two likely players: a restricted viral reservoir and an efficient cell
      mediated immune response. We previously showed that a combination of highly
      suppressive antiretroviral therapy and two experimental drugs, i.e., auranofin
      and buthionine sulfoximine, was able to reduce the viral reservoir, elicit
      efficient cell-mediated antiviral responses, and induce intermittent posttherapy
      viral load control in chronically SIVmac251-infected macaques. We here show that
      the macaques that had received this drug combination and then stopped
      antiretroviral therapy were also able to maintain low numbers of activated CD4+ T
      cells at viral rebound. Moreover, these macaques consistently displayed low-level
      simian immunodeficiency virus (SIV) diversity, which was in line with the strong
      and broadly reactive cell-mediated immune responses against conserved Gag
      antigens. Extended follow-up showed that the two macaques that had received the
      complete drug combination remained healthy and did not develop AIDS in 2 years of
      follow-up after therapy suspension. This disease-free survival is longer than
      twice the average time of progression to AIDS in SIVmac251-infected rhesus
      macaques. These results suggest that limited numbers of activated T cells at
      viral rebound and subsequent development of broadly reactive cell-mediated
      responses may be interrelated in reducing the viral reservoir. IMPORTANCE: The
      HIV reservoir in CD4+ T cells represents one main obstacle to HIV eradication.
      Recent studies, however, show that a drastic reduction of this reservoir is
      insufficient for inducing a functional cure of AIDS. In the present work, we
      thoroughly studied and subjected to long-term follow-up two macaques showing
      intermittent control of the virus following suspension of antiretroviral therapy
      plus an experimental antireservoir treatment, i.e., the gold salt auranofin and
      the investigational chemotherapeutic agent buthionione sulfoximine (BSO). We
      found that these drugs were able to decrease the number of activated CD4+ T
      cells, which are preferential targets for HIV infection. Then, efficient immune
      responses against the virus were developed in the macaques, which remained
      healthy during 2 years of follow-up. This result may furnish another building
      block for future attempts to cure HIV/AIDS.

PMID- 25972548
TI  - A Rhesus Rhadinovirus Viral Interferon (IFN) Regulatory Factor Is Virion
      Associated and Inhibits the Early IFN Antiviral Response.
AB  - The interferon (IFN) response is the earliest host immune response dedicated to
      combating viral infection. As such, viruses have evolved strategies to subvert
      this potent antiviral response. Two closely related gammaherpesviruses, Kaposi's
      sarcoma-associated herpesvirus (KSHV) and rhesus macaque rhadinovirus (RRV), are
      unique in that they express viral homologues to cellular interferon regulatory
      factors (IRFs), termed viral IRFs (vIRFs). Cellular IRFs are a family of
      transcription factors that are particularly important for the transcription of
      type I IFNs. Here, we demonstrate a strategy employed by RRV to ensure rapid
      inhibition of virus-induced type I IFN induction. We found that RRV vIRF R6, when
      expressed ectopically, interacts with a transcriptional coactivator, CREB-binding
      protein (CBP), in the nucleus. As a result, phosphorylated IRF3, an important
      transcriptional regulator in beta interferon (IFN-beta) transcription, fails to
      effectively bind to the IFN-beta promoter, thus inhibiting the activation of IFN
      beta genes. In addition, we found R6 within RRV virion particles via
      immunoelectron microscopy and, furthermore, that virion-associated R6 is capable
      of inhibiting the type I IFN response by preventing efficient binding of IRF3/CBP
      complexes to the IFN-beta promoter in the context of infection. The work shown
      here is the first example of a vIRF being associated with either the KSHV or RRV
      virion. The presence of this immunomodulatory protein in the RRV virion provides
      the virus with an immediate mechanism to evade the host IFN response, thus
      enabling the virus to effectively establish an infection within the host.
      IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) and the closely
      related rhesus macaque rhadinovirus (RRV) are the only viruses known to encode
      viral homologues to cellular interferon regulatory factors (IRFs), known as
      vIRFs. In KSHV, these proteins have been shown to play major roles in a variety
      of cellular processes and are particularly important in the evasion of the host
      type I interferon (IFN) response. In this study, we delineate the
      immunomodulatory mechanism of an RRV vIRF and its ability to assist the virus in
      rapid immune evasion by being prepackaged within the virion, thus providing
      evidence, for the first time, of a virion-associated vIRF. This work further
      contributes to our understanding of the mechanisms behind immunomodulation by the
      RRV vIRFs during infection.

PMID- 25972549
TI  - Isolation and Analysis of Rare Norovirus Recombinants from Coinfected Mice Using
      Drop-Based Microfluidics.
AB  - Human noroviruses (HuNoVs) are positive-sense RNA viruses that can cause severe,
      highly infectious gastroenteritis. HuNoV outbreaks are frequently associated with
      recombination between circulating strains. Strain genotyping and phylogenetic
      analyses show that noroviruses often recombine in a highly conserved region near
      the junction of the viral polyprotein (open reading frame 1 [ORF1]) and capsid
      (ORF2) genes and occasionally within the RNA-dependent RNA polymerase (RdRP)
      gene. Although genotyping methods are useful for tracking changes in circulating
      viral populations, they report only the dominant recombinant strains and do not
      elucidate the frequency or range of recombination events. Furthermore, the
      relatively low frequency of recombination in RNA viruses has limited studies to
      cell culture or in vitro systems, which do not reflect the complexities and
      selective pressures present in an infected organism. Using two murine norovirus
      (MNV) strains to model coinfection, we developed a microfluidic platform to
      amplify, detect, and recover individual recombinants following in vitro and in
      vivo coinfection. One-step reverse transcriptase PCR (RT-PCR) was performed in
      picoliter drops with primers that identified the wild-type and recombinant
      progenies and scanned for recombination breakpoints at ~1-kb intervals. We
      detected recombination between MNV strains at multiple loci spanning the viral
      protease, RdRP, and capsid ORFs and isolated individual recombinant RNA genomes
      that were present at a frequency of 1/300,000 or higher. This study is the first
      to examine norovirus recombination following coinfection of an animal and
      suggests that the exchange of RNA among viral genomes in an infected host occurs
      in multiple locations and is an important driver of genetic diversity.
      IMPORTANCE: RNA viruses increase diversity and escape host immune barriers by
      genomic recombination. Studies using a number of viral systems indicate that
      recombination occurs via template switching by the virus-encoded RNA-dependent
      RNA polymerase (RdRP). However, factors that govern the frequency and positions
      of recombination in an infected organism remain largely unknown. This work
      leverages advances in the applied physics of drop-based microfluidics to isolate
      and sequence rare recombinants arising from the coinfection of mice with two
      distinct strains of murine norovirus. This study is the first to detect and
      analyze norovirus recombination in an animal model.

PMID- 25972550
TI  - Complexity of Neutralizing Antibodies against Multiple Dengue Virus  Serotypes
      after Heterotypic Immunization and Secondary Infection  Revealed by In-Depth
      Analysis of Cross-Reactive Antibodies.
AB  - The four serotypes of dengue virus (DENV) cause the most important and rapidly
      emerging arboviral diseases in humans. The recent phase 2b and 3 studies of a
      tetravalent dengue vaccine reported a moderate efficacy despite the presence of
      neutralizing antibodies, highlighting the need for a better understanding of
      neutralizing antibodies in polyclonal human sera. Certain type-specific (TS)
      antibodies were recently discovered to account for the monotypic neutralizing
      activity and protection after primary DENV infection. The nature of neutralizing
      antibodies after secondary DENV infection remains largely unknown. In this study,
      we examined sera from 10 vaccinees with well-documented exposure to first and
      second DENV serotypes through heterotypic immunization with live-attenuated
      vaccines. Higher serum IgG avidities to both exposed and nonexposed serotypes
      were found after secondary immunization than after primary immunization. Using a
      two-step depletion protocol to remove different anti-envelope antibodies,
      including group-reactive (GR) and complex-reactive (CR) antibodies separately, we
      found GR and CR antibodies together contributed to more than 50% of neutralizing
      activities against multiple serotypes after secondary immunization. Similar
      findings were demonstrated in patients after secondary infection. Anti-envelope
      antibodies recognizing previously exposed serotypes consisted of a large
      proportion of GR antibodies, CR antibodies, and a small proportion of TS
      antibodies, whereas those recognizing nonexposed serotypes consisted of GRand CR
      antibodies. These findings have implications for sequential heterotypic
      immunization or primary immunization of DENV-primed individuals as alternative
      strategies for DENV vaccination. The complexity of neutralizing antibodies after
      secondary infection provides new insights into the difficulty of their
      application as surrogates of protection. IMPORTANCE: The four serotypes of dengue
      virus (DENV) are the leading cause of arboviral diseases in humans. Despite the
      presence of neutralizing antibodies, a moderate efficacy was recently reported in
      phase 2b and 3 trials of a dengue vaccine; a better understanding of neutralizing
      antibodies in polyclonal human sera is urgently needed.We studied vaccinees who
      received heterotypic immunization of live-attenuated vaccines, as they were known
      to have received the first and second DENV serotype exposures.We found anti
      envelope antibodies consist of group-reactive (GR), complex-reactive (CR), and
      type-specific (TS) antibodies, and that both GR and CR antibodies contribute
      significantly to multitypic neutralizing activities after secondary DENV
      immunization. These findings have implications for alternative strategies for
      DENV vaccination. Certain TS antibodies were recently discovered to contribute to
      the monotypic neutralizing activity and protection after primary DENV infection;
      our findings of the complexity of neutralizing activities after secondary
      immunization/infection provide new insights for neutralizing antibodies as
      surrogates of protection.

PMID- 25972552
TI  - Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr Virus
      Latent Membrane Protein 1 (LMP1) and LMP2A in Nasopharyngeal Carcinoma Cells.
AB  - Nasopharyngeal carcinoma (NPC) is closely associated with latent Epstein-Barr
      virus (EBV) infection. Although EBV infection of preneoplastic epithelial cells
      is not immortalizing, EBV can modulate oncogenic and cell death mechanisms. The
      viral latent membrane proteins 1 (LMP1) and LMP2A are consistently expressed in
      NPC and can cooperate in bitransgenic mice expressed from the keratin-14 promoter
      to enhance carcinoma development in an epithelial chemical carcinogenesis model.
      In this study, LMP1 and LMP2A were coexpressed in the EBV-negative NPC cell line
      HK1 and examined for combined effects in response to genotoxic treatments. In
      response to DNA damage activation, LMP1 and LMP2A coexpression reduced gammaH2AX
      (S139) phosphorylation and caspase cleavage induced by a lower dose (5 MUM) of
      the topoisomerase II inhibitor etoposide. Regulation of gammaH2AX occurred before
      the onset of caspase activation without modulation of other DNA damage signaling
      mediators, including ATM, Chk1, or Chk2, and additionally was suppressed by
      inducers of DNA single-strand breaks (SSBs) and replication stress. Despite
      reduced DNA damage repair signaling, LMP1-2A coexpressing cells recovered from
      cytotoxic doses of etoposide; however, LMP1 expression was sufficient for this
      effect. LMP1 and LMP2A coexpression did not enhance cell growth, with a moderate
      increase of cell motility to fibronectin. This study supports that LMP1 and LMP2A
      jointly regulate DNA repair signaling and cell death activation with no further
      enhancement in the growth properties of neoplastic cells. IMPORTANCE: NPC is
      characterized by clonal EBV infection and accounts for >78,000 annual cancer
      cases with increased incidence in regions where EBV is endemic, such as southeast
      Asia. The latent proteins LMP1 and LMP2A coexpressed in NPC can individually
      enhance growth or survival properties in epithelial cells, but their combined
      effects and potential regulation of DNA repair and checkpoint mechanisms are
      relatively undetermined. In this study, LMP1-2A coexpression suppressed
      activation of the DNA damage response (DDR) protein gammaH2AX induced by
      selective genotoxins that promote DNA replication stress or SSBs. Expression of
      LMP1 was sufficient to recover cells, resulting in outgrowth of LMP1 and LMP1-2A
      coexpressing cells and indicating distinct LMP1-dependent effects in the
      restoration of replicative potential. These findings demonstrate novel properties
      for LMP1 and LMP2A in the cooperative modulation of DDR and apoptotic signaling
      pathways, further implicating both proteins in the progression of NPC and
      epithelial malignancies.

PMID- 25972551
TI  - Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute
      HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine
      Research.
AB  - Eliciting broadly reactive functional antibodies remains a challenge in human
      immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by
      variations in envelope (Env) subtype and structure. The majority of new global
      HIV-1 infections are subtype C, and novel antigenic properties have been
      described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein
      (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was
      developed as a research reagent and candidate immunogen. The gp145 envelope is a
      novel immunogen with a fully intact membrane-proximal external region (MPER),
      extended by a polylysine tail. Soluble gp145 was enriched for trimers that
      yielded the expected "fan blade" motifs when visualized by cryoelectron
      microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1
      neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121,
      697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for
      immunogenicity in rabbits, and purified dimers, trimers, and larger multimers
      elicited similar levels of cross-subtype binding and neutralizing antibodies to
      tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the
      highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous
      infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay.
      This Env is currently in good manufacturing practice (GMP) production to be made
      available for use as a clinical research tool and further evaluation as a
      candidate vaccine. IMPORTANCE: At present, the product pipeline for HIV vaccines
      is insufficient and is limited by inadequate capacity to produce large quantities
      of vaccine to standards required for human clinical trials. Such products are
      required to evaluate critical questions of vaccine formulation, route, dosing,
      and schedule, as well as to establish vaccine efficacy. The gp145 Env protein
      presented in this study forms physical trimers, binds to many of the well
      characterized broad neutralizing MAbs that target conserved Env epitopes, and
      induce cross-subtype neutralizing antibodies as measured in both cell line and
      primary cell assays. This subtype C Env gp145 protein is currently undergoing
      good manufacturing practice production for use as a reagent for preclinical
      studies and for human clinical research. This product will serve as a reagent for
      comparative studies and may represent a next-generation candidate HIV immunogen.

PMID- 25972553
TI  - Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance
      Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and
      Subtype A/E Infections.
AB  - The effect of antiretroviral drug resistance mutations on cytotoxic T lymphocyte
      (CTL) recognition has been analyzed in HIV-1 subtype B infections, but it remains
      unclear in infections by other HIV-1 subtypes that are epidemic in countries
      where antiretroviral drugs are not effectively used. We investigated the effect
      of nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-resistance
      mutations (Y181C, Y181I, and Y181V) on epitope recognition by CTLs specific for 3
      different HIV-1 epitopes (HLA-A*02:01-restricted IV10, HLA-B*35:01-restricted
      NY9, and HLA-C*12:02-restricted KY9) in subtype B and subtype A/E infections and
      the accumulation of these mutations in treatment-naive Japanese and Vietnamese.
      These NNRTI-resistance mutations critically affected NY9-specific and KY9
      specific T cell responses in the subtype B infections, whereas they showed a
      different effect on IV10-specific T cell responses among the subtype B-infected
      individuals. These mutations affected IV10-specific T cell responses but weakly
      affected NY9-specific T cell responses in the subtype A/E infections. The
      substitution at position 3 of NY9 epitope which was found in the subtype A/E
      virus differently influenced the peptide binding to HLA-B*35:01, suggesting that
      the differences in peptide binding may result in the differences in T cell
      recognition between the subtype B virus and A/E virus infections. The Y181C
      mutation was found to be accumulating in treatment-naive Vietnamese infected with
      the subtype A/E virus. The present study demonstrated different effects of NNRTI
      resistance RT181 mutations on CTL responses between the 2 subtype infections. The
      Y181C mutation may influence HIV-1 control by the CTLs in Vietnam, since this
      mutation has been accumulating in treatment-naive Vietnamese. IMPORTANCE:
      Antiretroviral therapy leads to the emergence of drug-resistant HIV-1, resulting
      in virological and clinical failures. Though HIV-1-specific CTLs play a critical
      role in HIV-1 infection, some of drug resistance mutations located in CTL
      epitopes are known to affect HIV-1-specific CTL responses. Nonnucleoside reverse
      transcriptase inhibitor (NNRTI)-resistance RT181 mutations are frequently
      observed in patients treated with NNRTIs. Such drug resistance mutations may have
      an influence on immune control by HIV-1-specific CTLs, especially in countries
      where antiretroviral drugs are not effectively used. We here investigated the
      effect of three NNRTI-resistance RT181 mutations on immune responses by HIV-1
      specific CTLs and the recent accumulation of these mutations in treatment-naive
      Vietnamese infected with HIV-1 subtype A/E virus. RT181 mutations affected CTL
      recognition in both subtype A/E and B infections, while the RT Y181C mutation has
      been accumulating in treatment-naive Vietnamese. The results suggest that the
      Y181C mutation may influence HIV-1 control by CTLs in Vietnam.

PMID- 25972554
TI  - The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human
      Papillomavirus Replication through Epigenetic Modifications of the Viral
      Promoters.
AB  - The human interferon-inducible IFI16 protein, an innate immune sensor of
      intracellular DNA, was recently demonstrated to act as a restriction factor for
      human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1) infection by
      inhibiting both viral-DNA replication and transcription. Through the use of two
      distinct cellular models, this study provides strong evidence in support of the
      notion that IFI16 can also restrict human papillomavirus 18 (HPV18) replication.
      In the first model, an immortalized keratinocyte cell line (NIKS) was used, in
      which the IFI16 protein was knocked down through the use of small interfering RNA
      (siRNA) technology and overexpressed following transduction with the adenovirus
      IFI16 (AdVIFI16) vector. The second model consisted of U2OS cells transfected by
      electroporation with HPV18 minicircles. In differentiated IFI16-silenced NIKS
      HPV18 cells, viral-load values were significantly increased compared with
      differentiated control cells. Consistent with this, IFI16 overexpression severely
      impaired HPV18 replication in both NIKS and U2OS cells, thus confirming its
      antiviral restriction activity. In addition to the inhibition of viral
      replication, IFI16 was also able to reduce viral transcription, as demonstrated
      by viral-gene expression analysis in U2OS cells carrying episomal HPV18
      minicircles and HeLa cells. We also provide evidence that IFI16 promotes the
      addition of heterochromatin marks and the reduction of euchromatin marks on viral
      chromatin at both early and late promoters, thus reducing both viral replication
      and transcription. Altogether, these results argue that IFI16 restricts
      chromatinized HPV DNA through epigenetic modifications and plays a broad
      surveillance role against viral DNA in the nucleus that is not restricted to
      herpesviruses. IMPORTANCE: Intrinsic immunity is mediated by cellular restriction
      factors that are constitutively expressed and active even before a pathogen
      enters the cell. The host nuclear factor IFI16 acts as a sensor of foreign DNA
      and an antiviral restriction factor, as recently demonstrated by our group for
      human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1). Here, we provide
      the first evidence that IFI16 inhibits HPV18 replication by repressing viral-gene
      expression and replication. This antiviral restriction activity was observed in
      immortalized keratinocytes transfected with the religated genomes and in U2OS
      cells transfected with HPV18 minicircles, suggesting that it is not cell type
      specific. We also show that IFI16 promotes the assembly of heterochromatin on HPV
      DNA. These changes in viral chromatin structure lead to the generation of a
      repressive state at both early and late HPV18 promoters, thus implicating the
      protein in the epigenetic regulation of HPV gene expression and replication.

PMID- 25972555
TI  - Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines.
AB  - Several members of the Arenaviridae family cause hemorrhagic fever disease in
      humans and pose serious public health problems in their geographic regions of
      endemicity as well as a credible biodefense threat. To date, there have been no
      FDA-approved arenavirus vaccines, and current antiarenaviral therapy is limited
      to an off-label use of ribavirin that is only partially effective. Arenaviruses
      are enveloped viruses with a bisegmented negative-stranded RNA genome. Each
      genome segment uses an ambisense coding strategy to direct the synthesis of two
      viral polypeptides in opposite orientations, separated by a noncoding intergenic
      region. Here we have used minigenome-based approaches to evaluate expression
      levels of reporter genes from the nucleoprotein (NP) and glycoprotein precursor
      (GPC) loci within the S segment of the prototypic arenavirus lymphocytic
      choriomeningitis virus (LCMV). We found that reporter genes are expressed to
      higher levels from the NP than from the GPC locus. Differences in reporter gene
      expression levels from the NP and GPC loci were confirmed with recombinant
      trisegmented LCM viruses. We then used reverse genetics to rescue a recombinant
      LCMV (rLCMV) containing a translocated viral S segment (rLCMV/TransS), where the
      viral NP and GPC open reading frames replaced one another. The rLCMV/TransS
      showed slower growth kinetics in cultured cells and was highly attenuated in vivo
      in a mouse model of lethal LCMV infection, but immunization with rLCMV/TransS
      conferred complete protection against a lethal challenge with wild-type LCMV.
      Attenuation of rLCMV/TransS was associated with reduced NP expression levels.
      These results open a new avenue for the development of arenavirus live attenuated
      vaccines based on rearrangement of their viral genome. IMPORTANCE: Several
      arenaviruses cause severe hemorrhagic fever in humans and also pose a credible
      bioterrorism threat. Currently, no FDA-licensed vaccines are available to combat
      arenavirus infections and antiarenaviral therapy is limited to the off-label use
      of ribavirin, which is only partially effective and associated with side effects.
      Here we describe, for the first time, the generation of a recombinant LCMV where
      the viral protein products encoded by the S RNA segment (NP and GPC) were swapped
      to generate rLCMV/TransS. rLCMV/TransS exhibited reduced viral multiplication in
      cultured cells and was highly attenuated in vivo while conferring protection,
      upon a single immunization dose, against a lethal challenge with wild-type LCMV.
      Our studies provide a proof of concept for the rational development of safe and
      protective live attenuated vaccine candidates based on genome reorganization for
      the treatment of pathogenic arenavirus infections in humans.

PMID- 25972556
TI  - Phage Therapy: a Step Forward in the Treatment of Pseudomonas aeruginosa
      Infections.
AB  - Antimicrobial resistance constitutes one of the major worldwide public health
      concerns. Bacteria are becoming resistant to the vast majority of antibiotics,
      and nowadays, a common infection can be fatal. To address this situation, the use
      of phages for the treatment of bacterial infections has been extensively studied
      as an alternative therapeutic strategy. Since Pseudomonas aeruginosa is one of
      the most common causes of health care-associated infections, many studies have
      reported the in vitro and in vivo antibacterial efficacy of phage therapy against
      this bacterium. This review collects data of all the P. aeruginosa phages
      sequenced to date, providing a better understanding about their biodiversity.
      This review further addresses the in vitro and in vivo results obtained by using
      phages to treat or prevent P. aeruginosa infections as well as the major hurdles
      associated with this therapy. 

PMID- 25972557
TI  - Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus
      vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions.
AB  - Bats are important reservoirs for several viruses, many of which cause lethal
      infections in humans but have reduced pathogenicity in bats. As the innate immune
      response is critical for controlling viruses, the nature of this response in bats
      and how it may differ from that in other mammals are of great interest. Using
      next-generation transcriptome sequencing (mRNA-seq), we profiled the
      transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle
      disease virus (NDV), an avian paramyxovirus known to elicit a strong innate
      immune response in mammalian cells. The Pteropus genus is a known reservoir of
      Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200 to 300 regulated
      genes showed that genes for interferon (IFN) and antiviral pathways are highly
      upregulated in NDV-infected PVK cells, including genes for beta IFN, RIG-I, MDA5,
      ISG15, and IRF1. NDV-infected cells also upregulated several genes not previously
      characterized to be antiviral, such as RND1, SERTAD1, CHAC1, and MORC3. In fact,
      we show that MORC3 is induced by both IFN and NDV infection in PVK cells but is
      not induced by either stimulus in human A549 cells. In contrast to NDV infection,
      HeV and NiV infection of PVK cells failed to induce these innate immune response
      genes. Likewise, an attenuated response was observed in PVK cells infected with
      recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study
      provides the first global profile of a robust virus-induced innate immune
      response in bats and indicates that henipavirus IFN antagonist mechanisms are
      likely active in bat cells. IMPORTANCE: Bats are the reservoir host for many
      highly pathogenic human viruses, including henipaviruses, lyssaviruses, severe
      acute respiratory syndrome coronavirus, and filoviruses, and many other viruses
      have also been isolated from bats. Viral infections are reportedly asymptomatic
      or heavily attenuated in bat populations. Despite their ecological importance to
      viral maintenance, research into their immune system and mechanisms for viral
      control has only recently begun. Nipah virus and Hendra virus are two
      paramyxoviruses associated with high mortality rates in humans and whose
      reservoir is the Pteropus genus of bats. Greater knowledge of the innate immune
      response of P. vampyrus bats to viral infection may elucidate how bats serve as a
      reservoir for so many viruses.

PMID- 25972558
TI  - The Minor Capsid Protein VP11 of Thermophilic Bacteriophage P23-77 Facilitates
      Virus Assembly by Using Lipid-Protein Interactions.
AB  - Thermus thermophilus bacteriophage P23-77 is the type member of a new virus
      family of icosahedral, tailless, inner-membrane-containing double-stranded DNA
      (dsDNA) viruses infecting thermophilic bacteria and halophilic archaea. The
      viruses have a unique capsid architecture consisting of two major capsid proteins
      assembled in various building blocks. We analyzed the function of the minor
      capsid protein VP11, which is the third known capsid component in bacteriophage
      P23-77. Our findings show that VP11 is a dynamically elongated dimer with a
      predominantly alpha-helical secondary structure and high thermal stability. The
      high proportion of basic amino acids in the protein enables electrostatic
      interaction with negatively charged molecules, including nucleic acid and large
      unilamellar lipid vesicles (LUVs). The plausible biological function of VP11 is
      elucidated by demonstrating the interactions of VP11 with Thermus-derived LUVs
      and with the major capsid proteins by means of the dynamic-light-scattering
      technique. In particular, the major capsid protein VP17 was able to link VP11
      complexed LUVs into larger particles, whereas the other P23-77 major capsid
      protein, VP16, was unable to link VP11-comlexed LUVs. Our results rule out a
      previously suggested penton function for VP11. Instead, the electrostatic
      membrane association of VP11 triggers the binding of the major capsid protein
      VP17, thus facilitating a controlled incorporation of the two different major
      protein species into the assembling capsid. IMPORTANCE: The study of thermophilic
      viruses with inner membranes provides valuable insights into the mechanisms used
      for stabilization and assembly of protein-lipid systems at high temperatures. Our
      results reveal a novel way by which an internal membrane and outer capsid shell
      are linked in a virus that uses two different major protein species for capsid
      assembly. We show that a positive protein charge is important in order to form
      electrostatic interactions with the lipid surface, thereby facilitating the
      incorporation of other capsid proteins on the membrane surface. This implies an
      alternative function for basic proteins present in the virions of other lipid
      containing thermophilic viruses, whose proposed role in genome packaging is based
      on their capability to bind DNA. The unique minor capsid protein of bacteriophage
      P23-77 resembles in its characteristics the scaffolding proteins of tailed
      phages, though it constitutes a substantial part of the mature virion.

PMID- 25972559
TI  - Ability of the Encephalitic Arbovirus Semliki Forest Virus To Cross the Blood
      Brain Barrier Is Determined by the Charge of the E2 Glycoprotein.
AB  - Semliki Forest virus (SFV) provides a well-characterized model system to study
      the pathogenesis of virus encephalitis. Several studies have used virus derived
      from the molecular clone SFV4. SFV4 virus does not have the same phenotype as the
      closely related L10 or the prototype virus from which its molecular clone was
      derived. In mice, L10 generates a high-titer plasma viremia, is efficiently
      neuroinvasive, and produces a fatal panencephalitis, whereas low-dose SFV4
      produces a low-titer viremia, rarely enters the brain, and generally is
      avirulent. To determine the genetic differences responsible, the consensus
      sequence of L10 was determined and compared to that of SFV4. Of the 12 nucleotide
      differences, six were nonsynonymous; these were engineered into a new molecular
      clone, termed SFV6. The derived virus, SFV6, generated a high-titer viremia and
      was efficiently neuroinvasive and virulent. The phenotypic difference mapped to a
      single amino acid residue at position 162 in the E2 envelope glycoprotein (lysine
      in SFV4, glutamic acid in SFV6). Analysis of the L10 virus showed it contained
      different plaque phenotypes which differed in virulence. A lysine at E2 247
      conferred a small-plaque avirulent phenotype and glutamic acid a large-plaque
      virulent phenotype. Viruses with a positively charged lysine at E2 162 or 247
      were more reliant on glycosaminoglycans (GAGs) to enter cells and were selected
      for by passage in BHK-21 cells. Interestingly, viruses with the greatest reliance
      on binding to GAGs replicated to higher titers in the brain and more efficiently
      crossed an in vitro blood-brain barrier (BBB). IMPORTANCE: Virus encephalitis is
      a major disease, and alphaviruses, as highlighted by the recent epidemic of
      chikungunya virus (CHIKV), are medically important pathogens. In addition,
      alphaviruses provide well-studied experimental systems with extensive literature,
      many tools, and easy genetic modification. In this study, we elucidate the
      genetic basis for the difference in phenotype between SFV4 and the virus stocks
      from which it was derived and correct this by engineering a new molecular clone.
      We then use this clone in one comprehensive study to demonstrate that positively
      charged amino acid residues on the surface of the E2 glycoprotein, mediated by
      binding to GAGs, determine selective advantage and plaque size in BHK-21 cells,
      level of viremia in mice, ability to cross an artificial BBB, efficiency of
      replication in the brain, and virulence. Together with studies on Sindbis virus
      (SINV), this study provides an important advance in understanding alphavirus, and
      probably other virus, encephalitis.

PMID- 25972560
TI  - Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of
      HIV Viremia.
AB  - CD4+ T cells play a pivotal role in the control of chronic viral infections.
      Recently, nontraditional CD4+ T cell functions beyond helper effects have been
      described, and a role for cytolytic CD4+ T cells in the control of HIV infection
      has been suggested. We define here the transcriptional, phenotypic, and
      functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and
      multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells
      revealed a distinct transcriptional signature compared to Th1 CD4+ cells but
      shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore,
      HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative
      to HIV-specific CD8+ T cells and worked cooperatively in the elimination of
      virally infected cells. Interestingly, we found that cytolytic CD4+ T cells
      emerge early during acute HIV infection and tightly follow acute viral load
      trajectory. This emergence was associated to the early viral set point,
      suggesting an involvement in early control, in spite of CD4 T cell susceptibility
      to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent
      subset distinct from Th1 cells that show combined activity with CD8+ T cells in
      the long-term control of HIV infection. IMPORTANCE: The ability of the immune
      system to control chronic HIV infection is of critical interest to both vaccine
      design and therapeutic approaches. Much research has focused on the effect of the
      ability of CD8+ T cells to control the virus, while CD4+ T cells have been
      overlooked as effectors in HIV control due to the fact that they are
      preferentially infected. We show here that a subset of HIV-specific CD4+ T cells
      cooperate in the cytolytic control of HIV replication. Moreover, these cells
      represent a distinct subset of CD4+ T cells showing significant transcriptional
      and phenotypic differences compared to HIV-specific Th1 cells but with
      similarities to CD8+ T cells. These findings are important for our understanding
      of HIV immunopathology.

PMID- 25972561
TI  - Presence of a trs-Like Motif Promotes Rep-Mediated Wild-Type Adeno-Associated
      Virus Type 2 Integration.
AB  - High-throughput integration site (IS) analysis of wild-type adeno-associated
      virus type 2 (wtAAV2) in human dermal fibroblasts (HDFs) and HeLa cells revealed
      that juxtaposition of a Rep binding site (RBS) and terminal resolution site (trs)
      like motif leads to a 4-fold-increased probability of wtAAV integration.
      Electrophoretic mobility shift assays (EMSAs) confirmed binding of Rep to off
      target RBSs. For the first time, we show Rep protein off-target nicking activity,
      highlighting the importance of the nicking substrate for Rep-mediated
      integration. 

PMID- 25972563
TI  - Correction.

PMID- 25972564
TI  - Correction.

PMID- 25972565
TI  - Environmental Chemistry and Chemical Ecology of "Green Tide" Seaweed Blooms.
AB  - Green tides are large growths or accumulations of green seaweeds that have been
      increasing in magnitude and frequency around the world. Because green tides
      consist of vast biomasses of algae in a limited area and are often seasonal or
      episodic, they go through periods of rapid growth in which they take up large
      amounts of nutrients and dissolved gases and generate bioactive natural products
      that may be stored in the plants, released into the environment, or broken down
      during decomposition. As a result of the use and production of inorganic and
      organic compounds, the algae in these blooms can have detrimental impacts on
      other organisms. Here, we review some of the effects that green tides have on the
      chemistry of seawater and the effects of the natural products that they produce.
      As blooms are developing and expanding, algae in green tides take up inorganic
      nutrients, such as nitrate and ortho-phosphate, which can limit their
      availability to other photosynthetic organisms. Their uptake of dissolved
      inorganic carbon for use in photosynthesis can cause localized spikes in the pH
      of seawater during the day with concomitant drops in the pH at night when the
      algae are respiring. Many of the algae that form green-tide blooms produce
      allelopathic compounds, which are metabolites that affect other species. The best
      documented allelopathic compounds include dimethylsulfoniopropionate (DMSP),
      dopamine, and reactive oxygen species (ROS) and their breakdown products. DMSP
      and dopamine are involved in defenses against herbivores. Dopamine and ROS are
      released into seawater where they can be allelopathic or toxic to other
      organisms. Thus, these macroalgal blooms can have harmful effects on nearby
      organisms by altering concentrations of nutrients and dissolved gas in seawater
      and by producing and releasing allelopathic or toxic compounds. 

PMID- 25972566
TI  - Employing Phylogenomics to Resolve the Relationships among Cnidarians,
      Ctenophores, Sponges, Placozoans, and Bilaterians.
AB  - Despite an explosion in the amount of sequence data, phylogenomics has failed to
      settle controversy regarding some critical nodes on the animal tree of life.
      Understanding relationships among Bilateria, Ctenophora, Cnidaria, Placozoa, and
      Porifera is essential for studying how complex traits such as neurons, muscles,
      and gastrulation have evolved. Recent studies have cast doubt on the historical
      viewpoint that sponges are sister to all other animal lineages with recent
      studies recovering ctenophores as sister. However, the ctenophore-sister
      hypothesis has been criticized as unrealistic and caused by systematic error. We
      review past phylogenomic studies and potential causes of systematic error in an
      effort to identify areas that can be improved in future studies. Increased
      sampling of taxa, less missing data, and a priori removal of sequences and taxa
      that may cause systematic error in phylogenomic inference will likely be the most
      fruitful areas of focus when assembling future datasets. Ultimately, we foresee
      metazoan relationships being resolved with higher support in the near future, and
      we caution against dismissing novel hypotheses merely because they conflict with
      historical viewpoints of animal evolution. 

PMID- 25972567
TI  - Reevaluating Musculoskeletal Linkages in Suction-Feeding Fishes with X-Ray
      Reconstruction of Moving Morphology (XROMM).
AB  - Suction-feeding fishes encompass a vast diversity of morphologies and ecologies,
      but during feeding they all rely on musculoskeletal linkages and levers to
      transform the shortening of muscle into 3D expansion of the mouth cavity. To
      relate the shape of these skeletal elements to their function in expansion of the
      mouth, four-bar linkage models have been developed and widely used in studies of
      ecology, evolution, and development. However, we have lacked the ability to test
      the predictions of these 2D linkage models against the actual 3D motions of
      fishes' skulls. A new imaging method, X-ray Reconstruction of Moving Morphology
      (XROMM), now makes it possible to measure 3D skeletal motions relative to other
      bones within the head and relative to the fish's body, and thereby to examine
      directly the proposed linkages. We used XROMM to examine the opercular linkage,
      in which shortening of the levator operculi muscle is hypothesized to retract the
      operculum, and thereby the interoperculum and interoperculomandibular ligament to
      generate depression of the lower jaw about the quadratomandibular joint. XROMM
      animations of suction strikes in largemouth bass revealed that the operculum is
      indeed retracted relative to the suspensorium as the levator operculi muscle
      shortens and the jaw depresses. However, the four-bar model of this linkage
      overestimates the depression of the jaw by nearly a factor of two. Therefore,
      caution should be used in interpreting and applying the predictions of this
      linkage model. When we measured kinematics relative to the fish's body, we found
      that the operculum was relatively stable, whereas the suspensorium was elevated
      along with the neurocranium, pushing the quadratomandibular joint forward to
      produce depression of the jaw. Thus, it is the epaxial muscles elevating the
      neurocranium that powers depression of the jaw through the opercular linkage.
      However, the levator operculi muscle plays a crucial role in stabilizing the
      operculum to allow elevation of the head to produce depression of the lower jaw.
      These results support the role of cranial muscles in controlling and transmitting
      power from the axial muscles, rather than generating substantial power
      themselves. We also demonstrate the utility of XROMM for assessing the function
      of this, and other, cranial linkages in suction-feeding fishes. 

PMID- 25972568
TI  - Introduction to the Symposium-Unsteady Aquatic Locomotion with Respect to Eco
      Design and Mechanics.
AB  - The importance of unsteadiness in the aquatic environment has come to the
      forefront in understanding locomotor mechanics in nature. The impact of
      unsteadiness, starting with control of posture and trajectories during aquatic
      locomotion, is ultimately expressed in energy costs, morphology, and fitness.
      Unsteadiness from both internal and external perturbations for aquatic animals is
      important at scales ranging from micro to macro to global. 

PMID- 25972569
TI  - HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study.
AB  - Observationally, low levels of HDL cholesterol are consistently associated with
      increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing
      has been suggested as a novel therapeutic option to reduce the risk of type 2
      diabetes. Whether levels of HDL cholesterol are causally associated with type 2
      diabetes is unknown. In a prospective study of the general population (n =
      47,627), we tested whether HDL cholesterol-related genetic variants were
      associated with low HDL cholesterol levels and, in turn, with an increased risk
      of type 2 diabetes. HDL cholesterol-decreasing gene scores and allele numbers
      associated with up to -13 and -20% reductions in HDL cholesterol levels. The
      corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44
      (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were
      nonsignificant. Genetic risk ratios for type 2 diabetes for a 0.2 mmol/L
      reduction in HDL cholesterol were 0.91 (0.75-1.09) and 0.93 (0.78-1.11) for HDL
      cholesterol-decreasing gene scores and allele numbers, respectively, compared
      with the corresponding observational hazard ratio of 1.37 (1.32-1.42). In
      conclusion, genetically reduced HDL cholesterol does not associate with increased
      risk of type 2 diabetes, suggesting that the corresponding observational
      association is due to confounding and/or reverse causation. 

PMID- 25972570
TI  - Detection of Antibodies Directed to the N-Terminal Region of GAD Is Dependent on
      Assay Format and Contributes to Differences in the Specificity of GAD
      Autoantibody Assays for Type 1 Diabetes.
AB  - GAD autoantibodies (GADAs) are sensitive markers of islet autoimmunity and type 1
      diabetes. They form the basis of robust prediction models and are widely used for
      the recruitment of subjects at high risk of type 1 diabetes to prevention trials.
      However, GADAs are also found in many individuals at low risk of diabetes
      progression. To identify the sources of diabetes-irrelevant GADA reactivity, we
      analyzed data from the 2009 and 2010 Diabetes Autoantibody Standardization
      Program GADA workshop and found that binding of healthy control sera varied
      according to assay type. The characterization of control sera found positive by
      radiobinding assay (RBA), but negative by ELISA, showed that many of these sera
      reacted to epitopes in the N-terminal region of the molecule. This finding
      prompted development of an N-terminally truncated GAD65 radiolabel, (35)S
      GAD65(96-585), which improved the performance of most GADA RBAs participating in
      an Islet Autoantibody Standardization Program GADA substudy. These detailed
      workshop comparisons have identified a source of disease-irrelevant signals in
      GADA RBAs and suggest that N-terminally truncated GAD labels will enable more
      specific measurement of GADAs in type 1 diabetes. 

PMID- 25972572
TI  - Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity.
AB  - Low mitochondrial number and activity have been suggested as underlying factors
      in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which
      mitochondrial dysfunction manifests in adipose tissue after the onset of obesity
      remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from
      healthy monozygotic twin pairs, 22.8-36.2 years of age, who were discordant
      (DeltaBMI >3 kg/m(2), mean length of discordance 6.3 +/- 0.3 years, n = 26) and
      concordant (DeltaBMI <3 kg/m(2), n = 14) for body weight, and assessed their
      detailed mitochondrial metabolic characteristics: mitochondrial-related
      transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount,
      mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS)
      protein levels. We report global expressional downregulation of mitochondrial
      oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA
      dependent translation system, and protein levels of the OXPHOS machinery in the
      obese compared with the lean co-twins. Pathway analysis indicated downshifting of
      fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic
      acid cycle, which inversely correlated with adiposity, insulin resistance, and
      inflammatory cytokines. Our results suggest that mitochondrial biogenesis,
      oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in
      acquired obesity, and are associated with metabolic disturbances already at the
      preclinical stage. 

PMID- 25972571
TI  - Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin
      Resistance.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates
      insulin sensitivity by promoting hepatic insulin clearance. Liver-specific
      inactivation or global null-mutation of Ceacam1 impairs hepatic insulin
      extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and
      visceral obesity. In this study we investigated whether diet-induced insulin
      resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J
      mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days,
      causing hyperinsulinemia, insulin resistance, and elevation in hepatic
      triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression
      prevented hyperinsulinemia and markedly limited insulin resistance and hepatic
      lipid accumulation that were induced by prolonged high-fat intake. This was
      partly mediated by increased hepatic beta-fatty acid oxidation and energy
      expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1
      expression and that overexpressing CEACAM1 in liver curtailed diet-induced
      metabolic abnormalities by protecting hepatic insulin clearance. 

PMID- 25972573
TI  - Impact of Socioeconomic Status on Cardiovascular Disease and Mortality in 24,947
      Individuals With Type 1 Diabetes.
AB  - OBJECTIVE: Socioeconomic status (SES) is a powerful predictor of cardiovascular
      disease (CVD) and death. We examined the association in a large cohort of
      patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Clinical data from
      the Swedish National Diabetes Register were linked to national registers, whereby
      information on income, education, marital status, country of birth,
      comorbidities, and events was obtained. Patients were followed until a first
      incident event, death, or end of follow-up. The association between socioeconomic
      variables and the outcomes was modeled using Cox regression, with rigorous
      covariate adjustment. RESULTS: We included 24,947 patients. Mean (SD) age and
      follow-up was 39.1 (13.9) and 6.0 (1.0) years. Death and fatal/nonfatal CVD
      occurred in 926 and 1378 individuals. Compared with being single, being married
      was associated with 50% lower risk of death, cardiovascular (CV) death, and
      diabetes-related death. Individuals in the two lowest quintiles had twice as
      great a risk of fatal/nonfatal CVD, coronary heart disease, and stroke and
      roughly three times as great a risk of death, diabetes-related death, and CV
      death as individuals in the highest income quintile. Compared with having <=9
      years of education, individuals with a college/university degree had 33% lower
      risk of fatal/nonfatal stroke. Immigrants had 19%, 33%, and 45% lower risk of
      fatal/nonfatal CVD, all-cause death, and diabetes-related death, respectively,
      compared with Swedes. Men had 44%, 63%, and 29% greater risk of all-cause death,
      CV death, and diabetes-related death. CONCLUSIONS: Low SES increases the risk of
      CVD and death by a factor of 2-3 in type 1 diabetes.

PMID- 25972575
TI  - Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2
      Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial.
AB  - OBJECTIVE: Low vitamin D status has been associated with impaired glycemic
      control in patients with type 2 diabetes. The purpose of our study was to
      evaluate the effect of vitamin D supplementation on glycemic control in patients
      with type 2 diabetes. RESEARCH DESIGN AND METHODS: This randomized, double-blind,
      placebo-controlled trial was conducted in 275 adult patients with type 2 diabetes
      without insulin treatment. Patients were randomly assigned to receive either
      vitamin D3 (50,000 IU/month) or placebo for 6 months. To assess the primary
      outcome of the study, change in HbA(1c), we performed a linear regression
      analysis. RESULTS: Mean baseline serum 25-hydroxyvitamin D [25(OH)D] increased
      from 60.6 +/- 23.3 to 101.4 +/- 27.6 nmol/L and 59.1 +/- 23.2 to 59.8 +/- 23.2
      nmol/L in the vitamin D and placebo group, respectively. Mean baseline HbA(1c)
      was 6.8 +/- 0.5% (51 +/- 6 mmol/mol) in both groups. After 6 months, no effect
      was seen on HbA(1c) (mean difference: beta = 0.4 [95% CI -0.6 to 1.5]; P = 0.42)
      and other indicators of glycemic control (HOMA of insulin resistance, fasting
      insulin, and glucose) in the entire study population. Subgroup analysis in
      patients with a serum 25(OH)D <50 nmol/L or an HbA(1c) level >7% (53 mmol/mol)
      did not differ the results. CONCLUSIONS: In a well-controlled group of patients
      with type 2 diabetes, intermittent high-dose vitamin D supplementation did not
      improve glycemic control.

PMID- 25972576
TI  - Coronary artery disease affects cortical circuitry associated with brain-heart
      integration during volitional exercise.
AB  - This study tested the hypothesis that coronary artery disease (CAD) alters the
      cortical circuitry associated with exercise. Observations of changes in heart
      rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were
      made in 23 control subjects [control; 8 women; 63 +/- 11 yr; mean arterial
      pressure (MAP): 90 +/- 9 mmHg] (mean +/- SD) and 17 similarly aged CAD patients
      (4 women; 59 +/- 9 yr; MAP: 87 +/- 10 mmHg). Four repeated bouts each of 30%,
      40%, and 50% of maximal voluntary contraction (MVC) force (LAB session), and
      seven repeated bouts of isometric handgrip (IHG) at 40% MVC force (fMRI session),
      were performed, with each contraction lasting 20 s and separated by 40 s of rest.
      There was a main effect of group (P = 0.03) on HR responses across all IHG
      intensities. Compared with control, CAD demonstrated less task-dependent
      deactivation in the posterior cingulate cortex and medial prefrontal cortex, and
      reduced activation in the right anterior insula, bilateral precentral cortex, and
      occipital lobe (P < 0.05). When correlated with HR, CAD demonstrated reduced
      activation in the bilateral insula and posterior cingulate cortex, and reduced
      deactivation in the dorsal anterior cingulate cortex, and bilateral precentral
      cortex (P < 0.05). The increased variability in expected autonomic regions and
      decrease in total cortical activation in response to the IHG task are associated
      with a diminished HR response to volitional effort in CAD. Therefore, relative to
      similarly aged and healthy individuals, CAD impairs the heart rate response and
      modifies the cortical patterns associated with cardiovascular control during IHG.

PMID- 25972577
TI  - D1 and D2 antagonists reverse the effects of appetite suppressants on weight
      loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc
      shell.
AB  - Obesity is a worldwide health problem that has reached epidemic proportions. To
      ameliorate this problem, one approach is the use of appetite suppressants. These
      compounds are frequently amphetamine congeners such as diethylpropion (DEP),
      phentermine (PHEN), and bupropion (BUP), whose effects are mediated through
      serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc)
      shell receives dopaminergic inputs and is involved in feeding and motor activity.
      However, little is known about how appetite suppressants modulate its activity.
      Therefore, we characterized behavioral and neuronal NAc shell responses to short
      term treatments of DEP, PHEN, and BUP. These compounds caused a transient
      decrease in weight and food intake while increasing locomotion, stereotypy, and
      insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity
      that correlated with the onset of locomotion and stereotypy. Analysis of the
      local field potentials (LFPs) showed that all three drugs modulated beta, theta,
      and delta oscillations. These oscillations do not reflect an aversive-malaise
      brain state, as ascertained from taste aversion experiments, but tracked both the
      initial decrease in weight and food intake and the subsequent tolerance to these
      drugs. Importantly, the appetite suppressant-induced weight loss and locomotion
      were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine
      antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore,
      both antagonists attenuated appetite suppressant-induced LFP oscillations and
      partially restored the imbalance in NAc shell activity. These data reveal that
      appetite suppressant-induced behavioral and neuronal activity recorded in the NAc
      shell depend, to various extents, on dopaminergic activation and thus point to an
      important role for D1/D2-like receptors (in the NAc shell) in the mechanism of
      action for these anorexic compounds. 

PMID- 25972578
TI  - Complex inhibitory microcircuitry regulates retinal signaling near visual
      threshold.
AB  - Neuronal microcircuits, small, localized signaling motifs involving two or more
      neurons, underlie signal processing and computation in the brain.
      Compartmentalized signaling within a neuron may enable it to participate in
      multiple, independent microcircuits. Each A17 amacrine cell in the mammalian
      retina contains within its dendrites hundreds of synaptic feedback microcircuits
      that operate independently to modulate feedforward signaling in the inner retina.
      Each of these microcircuits comprises a small (<1 MUm) synaptic varicosity that
      typically receives one excitatory synapse from a presynaptic rod bipolar cell
      (RBC) and returns two reciprocal inhibitory synapses back onto the same RBC
      terminal. Feedback inhibition from the A17 sculpts the feedforward signal from
      the RBC to the AII, a critical component of the circuitry mediating night vision.
      Here, we show that the two inhibitory synapses from the A17 to the RBC express
      kinetically distinct populations of GABA receptors: rapidly activating GABA(A)Rs
      are enriched at one synapse while more slowly activating GABA(C)Rs are enriched
      at the other. Anatomical and electrophysiological data suggest that
      macromolecular complexes of voltage-gated (Cav) channels and Ca(2+)-activated
      K(+) channels help to regulate GABA release from A17 varicosities and limit
      GABA(C)R activation under certain conditions. Finally, we find that selective
      elimination of A17-mediated feedback inhibition reduces the signal to noise ratio
      of responses to dim flashes recorded in the feedforward pathway (i.e., the AII
      amacrine cell). We conclude that A17-mediated feedback inhibition improves the
      signal to noise ratio of RBC-AII transmission near visual threshold, thereby
      improving visual sensitivity at night.

PMID- 25972579
TI  - Brief anesthesia, but not voluntary locomotion, significantly alters cortical
      temperature.
AB  - Changes in brain temperature can alter electrical properties of neurons and cause
      changes in behavior. However, it is not well understood how behaviors, like
      locomotion, or experimental manipulations, like anesthesia, alter brain
      temperature. We implanted thermocouples in sensorimotor cortex of mice to
      understand how cortical temperature was affected by locomotion, as well as by
      brief and prolonged anesthesia. Voluntary locomotion induced small (~ 0.1 
      degrees C) but reliable increases in cortical temperature that could be described
      using a linear convolution model. In contrast, brief (90-s) exposure to
      isoflurane anesthesia depressed cortical temperature by ~ 2  degrees C, which
      lasted for up to 30 min after the cessation of anesthesia. Cortical temperature
      decreases were not accompanied by a concomitant decrease in the gamma-band local
      field potential power, multiunit firing rate, or locomotion behavior, which all
      returned to baseline within a few minutes after the cessation of anesthesia. In
      anesthetized animals where core body temperature was kept constant, cortical
      temperature was still > 1  degrees C lower than in the awake animal.
      Thermocouples implanted in the subcortex showed similar temperature changes under
      anesthesia, suggesting these responses occur throughout the brain. Two-photon
      microscopy of individual blood vessel dynamics following brief isoflurane
      exposure revealed a large increase in vessel diameter that ceased before the
      brain temperature significantly decreased, indicating cerebral heat loss was not
      due to increased cerebral blood vessel dilation. These data should be considered
      in experimental designs recording in anesthetized preparations, computational
      models relating temperature and neural activity, and awake-behaving methods that
      require brief anesthesia before experimental procedures.

PMID- 25972580
TI  - Sound frequency-invariant neural coding of a frequency-dependent cue to sound
      source location.
AB  - The century-old duplex theory of sound localization posits that low- and high
      frequency sounds are localized with two different acoustical cues, interaural
      time and level differences (ITDs and ILDs), respectively. While behavioral
      studies in humans and behavioral and neurophysiological studies in a variety of
      animal models have largely supported the duplex theory, behavioral sensitivity to
      ILD is curiously invariant across the audible spectrum. Here we demonstrate that
      auditory midbrain neurons in the chinchilla (Chinchilla lanigera) also encode
      ILDs in a frequency-invariant manner, efficiently representing the full range of
      acoustical ILDs experienced as a joint function of sound source frequency,
      azimuth, and distance. We further show, using Fisher information, that nominal
      "low-frequency" and "high-frequency" ILD-sensitive neural populations can
      discriminate ILD with similar acuity, yielding neural ILD discrimination
      thresholds for near-midline sources comparable to behavioral discrimination
      thresholds estimated for chinchillas. These findings thus suggest a revision to
      the duplex theory and reinforce ecological and efficiency principles that hold
      that neural systems have evolved to encode the spectrum of biologically relevant
      sensory signals to which they are naturally exposed. 

PMID- 25972581
TI  - The physiology of perception in human temporal lobe is specialized for contextual
      novelty.
AB  - The human ventral temporal cortex has regions that are known to selectively
      process certain categories of visual inputs; they are specialized for the content
      ("faces," "places," "tools") and not the form ("line," "patch") of the image
      being seen. In our study, human patients with implanted electrocorticography
      (ECoG) electrode arrays were shown sequences of simple face and house pictures.
      We quantified neuronal population activity, finding robust face-selective sites
      on the fusiform gyrus and house-selective sites on the lingual/parahippocampal
      gyri. The magnitude and timing of single trials were compared between novel
      ("house-face") and repeated ("face-face") stimulus-type responses. More than half
      of the category-selective sites showed significantly greater total activity for
      novel stimulus class. Approximately half of the face-selective sites (and none of
      the house-selective sites) showed significantly faster latency to peak (~ 50 ms)
      for novel stimulus class. This establishes subregions within category-selective
      areas that are differentially tuned to novelty in sequential context, where novel
      stimuli are processed faster in some regions, and with increased activity in
      others.

PMID- 25972574
TI  - Improving Adiponectin Levels in Individuals With Diabetes and Obesity: Insights
      From Look AHEAD.
AB  - OBJECTIVE: This study investigated whether fitness changes resulting from
      lifestyle interventions for weight loss may independently contribute to the
      improvement of low adiponectin levels in obese individuals with diabetes.
      RESEARCH DESIGN AND METHODS: Look AHEAD (Action for Health in Diabetes)
      randomized overweight/obese individuals with type 2 diabetes to intensive
      lifestyle intervention (ILI) for weight loss or to diabetes support and education
      (DSE). Total and high-molecular weight adiponectin (adiponectins), weight, and
      cardiorespiratory fitness (submaximal exercise stress test) were measured in
      1,397 participants at baseline and at 1 year, when ILI was most intense.
      Regression analyses examined the associations of 1-year weight and fitness
      changes with change in adiponectins. RESULTS: ILI resulted in greater
      improvements in weight, fitness, and adiponectins at 1 year compared with DSE (P
      < 0.0001). Weight loss and improved fitness were each associated with changes in
      adiponectins in men and women (P < 0.001 for all), after adjusting for baseline
      adiponectins, demographics, clinical variables, and treatment arm. Weight loss
      contributed an additional 4-5% to the variance of change in adiponectins than did
      increased fitness in men; in women, the contributions of improved fitness (1%
      greater) and of weight loss were similar. When weight and fitness changes were
      both accounted for, weight loss in men and increased fitness in women retained
      their strong associations (P < 0.0001) with adiponectin change. CONCLUSIONS:
      Improvements in fitness and weight with ILI were favorably but distinctly
      associated with changes in adiponectin levels in overweight/obese men and women
      with diabetes. Future studies need to investigate whether sex-specific biological
      determinants contribute to the observed associations.

PMID- 25972582
TI  - Spinal sensory projection neuron responses to spinal cord stimulation are
      mediated by circuits beyond gate control.
AB  - Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a
      putative mechanism of action based on the Gate Control Theory. We hypothesized
      that sensory projection neuron responses to SCS would follow a single stereotyped
      response curve as a function of SCS frequency, as predicted by the Gate Control
      circuit. We recorded the responses of antidromically identified sensory
      projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both
      healthy rats and neuropathic rats following chronic constriction injury (CCI).
      The relationship between SCS frequency and projection neuron activity predicted
      by the Gate Control circuit accounted for a subset of neuronal responses to SCS
      but could not account for the full range of observed responses. Heterogeneous
      responses were classifiable into three additional groups and were reproduced
      using computational models of spinal microcircuits representing other
      interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal
      administration of bicuculline, a GABAA receptor antagonist, increased spontaneous
      and evoked activity in projection neurons, enhanced excitatory responses to SCS,
      and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission
      plays a broad role in regulating projection neuron activity. These in vivo and
      computational results challenge the Gate Control Theory as the only mechanism
      underlying SCS and refine our understanding of the effects of SCS on spinal
      sensory neurons within the framework of contemporary understanding of dorsal horn
      circuitry. 

PMID- 25972583
TI  - Graded boosting of synaptic signals by low-threshold voltage-activated calcium
      conductance.
AB  - Low-threshold voltage-activated calcium conductances (LT-VACCs) play a
      substantial role in shaping the electrophysiological attributes of neurites. We
      have investigated how these conductances affect synaptic integration in a
      premotor nonspiking (NS) neuron of the leech nervous system. These cells exhibit
      an extensive neuritic tree, do not fire Na(+)-dependent spikes, but express an LT
      VACC that was sensitive to 250 MUM Ni(2+) and 100 MUM NNC 55-0396 (NNC). NS
      neurons responded to excitation of mechanosensory pressure neurons with
      depolarizing responses for which amplitude was a linear function of the
      presynaptic firing frequency. NNC decreased these synaptic responses and
      abolished the concomitant widespread Ca(2+) signals. Coherent with the
      interpretation that the LT-VACC amplified signals at the postsynaptic level, this
      conductance also amplified the responses of NS neurons to direct injection of
      sinusoidal current. Synaptic amplification thus is achieved via a positive
      feedback in which depolarizing signals activate an LT-VACC that, in turn, boosts
      these signals. The wide distribution of LT-VACC could support the active
      propagation of depolarizing signals, turning the complex NS neuritic tree into a
      relatively compact electrical compartment. 

PMID- 25972584
TI  - Decision making: effects of methylphenidate on temporal discounting in nonhuman
      primates.
AB  - Decisions are often made based on which option will result in the largest reward.
      When given a choice between a smaller but immediate reward and a larger delayed
      reward, however, humans and animals often choose the smaller, an effect known as
      temporal discounting. Dopamine (DA) neurotransmission is central to reward
      processing and encodes delayed reward value. Impulsivity, the tendency to act
      without forethought, is associated with excessive discounting of rewards, which
      has been documented in patients with attention deficit hyperactivity disorder
      (ADHD). Both impulsivity and temporal discounting are linked to the dopaminergic
      system. Methylphenidate (MPH), which blocks the DA transporter and increases
      extracellular levels of DA in the basal ganglia and prefrontal cortex, is a
      primary treatment for ADHD and, at low doses, ameliorates impulsivity in both
      humans and animals. This study tested the hypothesis that low doses of MPH would
      decrease the discounting rate of rhesus monkeys performing an intertemporal
      choice task, suggesting a reduction in impulsivity. The results support this
      hypothesis and provide further evidence for the role of DA in temporal
      discounting and impulsive behavior. 

PMID- 25972585
TI  - Properties of precise firing synchrony between synaptically coupled cortical
      interneurons depend on their mode of coupling.
AB  - Precise spike synchrony has been widely reported in the central nervous system,
      but its functional role in encoding, processing, and transmitting information is
      yet unresolved. Of particular interest is firing synchrony between inhibitory
      cortical interneurons, thought to drive various cortical rhythms such as gamma
      oscillations, the hallmark of cognitive states. Precise synchrony can arise
      between two interneurons connected electrically, through gap junctions,
      chemically, through fast inhibitory synapses, or dually, through both types of
      connections, but the properties of synchrony generated by these different modes
      of connectivity have never been compared in the same data set. In the present
      study we recorded in vitro from 152 homotypic pairs of two major subtypes of
      mouse neocortical interneurons: parvalbumin-containing, fast-spiking (FS)
      interneurons and somatostatin-containing (SOM) interneurons. We tested firing
      synchrony when the two neurons were driven to fire by long, depolarizing current
      steps and used a novel synchrony index to quantify the strength of synchrony, its
      temporal precision, and its dependence on firing rate. We found that SOM-SOM
      synchrony, driven solely by electrical coupling, was less precise than FS-FS
      synchrony, driven by inhibitory or dual coupling. Unlike SOM-SOM synchrony, FS-FS
      synchrony was strongly firing rate dependent and was not evident at the
      prototypical 40-Hz gamma frequency. Computer simulations reproduced these
      differences in synchrony without assuming any differences in intrinsic
      properties, suggesting that the mode of coupling is more important than the
      interneuron subtype. Our results provide novel insights into the mechanisms and
      properties of interneuron synchrony and point out important caveats in current
      models of cortical oscillations. 

PMID- 25972587
TI  - Generalization patterns for reach adaptation and proprioceptive recalibration
      differ after visuomotor learning.
AB  - Visuomotor learning results in changes in both motor and sensory systems
      (Cressman EK, Henriques DY. J Neurophysiol 102: 3505-3518, 2009), such that
      reaches are adapted and sense of felt hand position recalibrated after reaching
      with altered visual feedback of the hand. Moreover, visuomotor learning has been
      shown to generalize such that reach adaptation achieved at a trained target
      location can influence reaches to novel target directions (Krakauer JW, Pine ZM,
      Ghilardi MF, Ghez C. J Neurosci 20: 8916-8924, 2000). We looked to determine
      whether proprioceptive recalibration also generalizes to novel locations.
      Moreover, we looked to establish the relationship between reach adaptation and
      changes in sense of felt hand position by determining whether proprioceptive
      recalibration generalizes to novel targets in a similar manner as reach
      adaptation. On training trials, subjects reached to a single target with aligned
      or misaligned cursor-hand feedback, in which the cursor was either rotated or
      scaled in extent relative to hand movement. After reach training, subjects
      reached to the training target and novel targets (including targets from a second
      start position) without visual feedback to assess generalization of reach
      adaptation. Subjects then performed a proprioceptive estimation task, in which
      they indicated the position of their hand relative to visual reference markers
      placed at similar locations as the trained and novel reach targets. Results
      indicated that shifts in hand position generalized across novel locations,
      independent of reach adaptation. Thus these distinct sensory and motor
      generalization patterns suggest that reach adaptation and proprioceptive
      recalibration arise from independent error signals and that changes in one system
      cannot guide adjustments in the other. 

PMID- 25972586
TI  - Modeling fMRI signals can provide insights into neural processing in the cerebral
      cortex.
AB  - Every stimulus or task activates multiple areas in the mammalian cortex. These
      distributed activations can be measured with functional magnetic resonance
      imaging (fMRI), which has the best spatial resolution among the noninvasive brain
      imaging methods. Unfortunately, the relationship between the fMRI activations and
      distributed cortical processing has remained unclear, both because the coupling
      between neural and fMRI activations has remained poorly understood and because
      fMRI voxels are too large to directly sense the local neural events. To get an
      idea of the local processing given the macroscopic data, we need models to
      simulate the neural activity and to provide output that can be compared with fMRI
      data. Such models can describe neural mechanisms as mathematical functions
      between input and output in a specific system, with little correspondence to
      physiological mechanisms. Alternatively, models can be biomimetic, including
      biological details with straightforward correspondence to experimental data.
      After careful balancing between complexity, computational efficiency, and
      realism, a biomimetic simulation should be able to provide insight into how
      biological structures or functions contribute to actual data processing as well
      as to promote theory-driven neuroscience experiments. This review analyzes the
      requirements for validating system-level computational models with fMRI. In
      particular, we study mesoscopic biomimetic models, which include a limited set of
      details from real-life networks and enable system-level simulations of neural
      mass action. In addition, we discuss how recent developments in neurophysiology
      and biophysics may significantly advance the modelling of fMRI signals. 

PMID- 25972588
TI  - Distinct ensembles of medial prefrontal cortex neurons are activated by
      threatening stimuli that elicit excitation vs. inhibition of movement.
AB  - Neural circuits controlling defensive behavior were investigated by recording
      single units in medial prefrontal cortex (mPFC) and dorsolateral periaqueductal
      gray (dlPAG) while rats expressed conditioned fear responses to an auditory
      conditioned stimulus (CS; 20-s train of white noise pips) previously paired with
      an aversive unconditioned stimulus (US; 2-s train of periorbital shocks). The CS
      elicited conditioned movement inhibition (CMI; characterized by decreased
      movement speed and freezing) when rats had not recently encountered the US,
      whereas the CS elicited conditioned movement excitation (CME; characterized by
      increased movement speed and flight behavior) after recent US encounters. Many
      mPFC neurons were "strategy-selective" cells that changed their firing rates only
      when the CS elicited CME (15/71) or CMI (13/71) responses, whereas few mPFC cells
      (4/71) responded nonselectively to the CS during either response. By contrast,
      many dlPAG neurons (20/74) responded nonselectively to the CS, but most (40/74)
      were excited by the CS selectively during CME trials (and none during CMI
      trials). CME-selective neurons in dlPAG responded phasically after CS pips that
      elicited CME responses, whereas CME-selective neurons in mPFC showed tonically
      elevated activity before and after pips that evoked CME responses. These findings
      suggest that, at the time when the CS occurs, tonic firing rates of CME- and CMI
      selective mPFC neurons may bias the rat's choice of whether to express CME vs.
      CMI responses, perhaps via projections to downstream structures (such as amygdala
      and PAG) that influence how sensory stimuli are mapped onto motor circuits that
      drive the expression of competing behaviors. 

PMID- 25972589
TI  - Age-related changes of auditory brainstem responses in nonhuman primates.
AB  - Nonhuman primates, compared with humans and rodents, have historically been far
      less used for studies of age-related hearing loss, primarily because of their
      long life span and high cost of maintenance. Strong similarities in genetics,
      anatomy, and neurophysiology of the auditory nervous system between humans and
      monkeys, however, could provide fruitful opportunities to enhance our
      understanding of hearing loss. The present study used a common, noninvasive
      technique for testing hearing sensitivity in humans, the auditory brainstem
      response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of
      age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys,
      particularly those above 21.5 yr of age, had missing ABR waveforms at high
      frequencies. Regression analyses revealed that ABR threshold increased as a
      function of age at peaks II and IV simultaneously. In the suprathreshold hearing
      condition (70 dB peak sound pressure level), ABR-based audiograms similarly
      varied as a function of age such that old monkeys had smaller peak amplitudes and
      delayed latencies at low, middle, and high frequencies. Peripheral hearing
      differences remained a major influence associated with age-related changes in
      audiometric functions of old monkeys at a comparable sensation level across
      animals. The present findings suggest that hearing loss occurs in old monkeys
      across a wide range of frequencies and that these deficits increase in severity
      with age. Parallel to prior studies in monkeys, we found weak effects of sex on
      hearing, and future investigations are necessary to clarify its role in age
      related hearing loss. 

PMID- 25972591
TI  - Goals of care are important for older adults with severe illness and their
      families, and are infrequently addressed by health professionals.

PMID- 25972592
TI  - Long-term follow-up of 82 patients after surgical excision of atrial myxomas.
AB  - OBJECTIVES: Literature reporting on large patient groups with the long-term
      follow-up is limited due to the low incidence of myxomas. This single-centre,
      retrospective study reports on the long-term follow-up (e.g. complications,
      recurrence and survival) of a substantial patient group operated for cardiac
      myxomas. METHODS: Patients were retrospectively selected from a prospectively
      obtained database comprising patients who had undergone cardiac surgery in the
      Catharina Hospital from 1990 onwards. Baseline characteristics and perioperative
      data were obtained from the database. In case of insufficient information,
      medical reports were analysed. The echocardiogram and clinical follow-up data
      were collected at outpatient clinics. RESULTS: Eighty-two patients were included,
      of which 48 were females with a mean age of 61.3 years (+/-13.8). The main
      presenting symptom was dyspnoea (29.3%), followed by chest pain (24.4%),
      palpitations (19.5%) and embolism (15.9%). Atrial fibrillation was the most
      frequent complication; directly postoperative (22%) and at the long-term follow
      up (26.3%). The follow-up was completed in 95.1%, with a mean echocardiographic
      follow-up time of 72 months and with a longest follow-up of almost 23 years.
      There were no myxoma recurrences. Thirteen patients (16.5%) deceased during the
      follow-up, with a mean time of 9 years after surgery. CONCLUSIONS: Myxomas carry
      the risk of severe complications. Surgical excision is the only option of
      treatment and gives excellent early and long-term results. Recurrence rates are
      low in case of non-hereditary myxomas, even in case of irradical excision. The
      echocardiographic follow-up therefore could be called into question.

PMID- 25972590
TI  - Increased spinal reflex excitability is associated with enhanced central
      activation during voluntary lengthening contractions in human spinal cord injury.
AB  - This study of chronic incomplete spinal cord injury (SCI) subjects investigated
      patterns of central motor drive (i.e., central activation) of the plantar flexors
      using interpolated twitches, and modulation of soleus H-reflexes during
      lengthening, isometric, and shortening muscle actions. In a recent study of the
      knee extensors, SCI subjects demonstrated greater central activation ratio (CAR)
      values during lengthening (i.e., eccentric) maximal voluntary contractions
      (MVCs), compared with during isometric or shortening (i.e., concentric) MVCs. In
      contrast, healthy controls demonstrated lower lengthening CAR values compared
      with their isometric and shortening CARs. For the present investigation, we
      hypothesized SCI subjects would again produce their highest CAR values during
      lengthening MVCs, and that these increases in central activation were partially
      attributable to greater efficacy of Ia-alpha motoneuron transmission during
      muscle lengthening following SCI. Results show SCI subjects produced higher CAR
      values during lengthening vs. isometric or shortening MVCs (all P < 0.001). H
      reflex testing revealed normalized H-reflexes (maximal SOL H-reflex-to-maximal M
      wave ratios) were greater for SCI than controls during passive (P = 0.023) and
      active (i.e., 75% MVC; P = 0.017) lengthening, suggesting facilitation of Ia
      transmission post-SCI. Additionally, measures of spinal reflex excitability
      (passive lengthening maximal SOL H-reflex-to-maximal M-wave ratio) in SCI were
      positively correlated with soleus electromyographic activity and CAR values
      during lengthening MVCs (both P < 0.05). The present study presents evidence that
      patterns of dynamic muscle activation are altered following SCI, and that greater
      central activation during lengthening contractions is partly due to enhanced
      efficacy of Ia-alpha motoneuron transmission. 

PMID- 25972593
TI  - Chylous pericardial effusion as a rare complication after pulmonary
      endarterectomy.
AB  - Chylous pericardial effusion is a rare complication of cardiac surgery. We report
      a case of a patient who underwent pulmonary endarterectomy for chronic
      thromboembolic pulmonary hypertension and was diagnosed with chylopericardium
      after the procedure. We present the surgical management of this condition, which
      included bilateral pedal lymphangiography followed by ligation of injured lymph
      vessel. 

PMID- 25972594
TI  - In vitro evaluation of physiological spiral anastomoses for the arterial switch
      operation in simple transposition of the great arteries: a first step towards a
      surgical alternative?
AB  - OBJECTIVES: The currently most frequently used technique for the arterial switch
      operation (ASO) in simple transposition of the great arteries (TGA) includes the
      transposition of the pulmonary artery anterior to the ascending aorta. This
      arterial arrangement is less anatomical, and although the initial results are
      excellent, some long-term data are indicating a certain risk of morbidity,
      encouraging the search for more physiological techniques. As a first step, we
      studied the feasibility of anatomical spiral anastomoses of the great vessels in
      vitro. METHODS: A TGA model was constructed to simulate the different spatial
      positions of the great arteries followed by ASO with physiological spiral
      connections of the great arteries. RESULTS: It was possible to perform a
      physiological spiral connection of the great arteries without tension or torsion
      when the roots of the great vessels were arranged anterior-posterior and with up
      to 35 degrees  rotation of the aortic root to the right around the pulmonary
      root. With further rotation of the aorta, patch plasties were required for
      pulmonary artery elongation. The maximal width of the patch was 5 mm.
      CONCLUSIONS: In this TGA model, it was possible to perform tension- and torsion
      free arterial anastomoses for ASO without artificial material, when the aortic
      root was positioned from 0 degrees  up to 35 degrees  to the right of the
      pulmonary root. Evaluation of coronary transfer is the next step.

PMID- 25972595
TI  - Truncus arteriosus, tricuspid atresia and partial anomalous pulmonary venous
      drainage: a unique form of univentricular heart.
AB  - We present the first reported case of truncus arteriosus, tricuspid atresia and
      partial anomalous pulmonary venous drainage into a retro-aortic innominate vein
      in a neonate in whom successful palliation was performed using a two-staged
      procedure. An early repair after presentation along with a re-routing of
      anomalous pulmonary venous drainage at the time of the second stage should be
      undertaken to optimize the patient's haemodynamic status prior to a Fontan
      completion. 

PMID- 25972596
TI  - Decellularized porcine aortic intima-media as a potential cardiovascular
      biomaterial.
AB  - OBJECTIVES: The aim of this research is to investigate the histological and
      mechanical properties of decellularized aortic intima-media, a promising
      cardiovascular biomaterial. METHODS: Porcine aortic intima-media was
      decellularized using two methods: high hydrostatic pressurization (HHP) and
      sodium dodecyl sulphate (SDS). The histological properties were characterized
      using haematoxylin and eosin staining and Elastica van Gieson staining. The
      mechanical properties were evaluated using a tensile strength test. RESULTS: The
      structure of the HHP-treated samples was unchanged histologically, whereas that
      of the SDS-treated samples appeared structurally loose. Consequently, with regard
      to the mechanical properties of SDS-decellularized intima-media, elastic modulus
      and tensile strength were significantly decreased. CONCLUSIONS: The
      decellularization method affected the structure and the mechanical properties of
      the biomaterial. The HHP-treated sample was structurally and mechanically similar
      to the untreated control. Its mechanical properties were similar to those of
      human heart valves and the iliac artery and vein. Our results imply that porcine
      aortic intima-media that is decellularized with HHP is a potential cardiovascular
      biomaterial.

PMID- 25972597
TI  - Imatinib for sclerodermatous graft-versus-host disease in lung transplantation.
AB  - Imatinib has been proposed as a treatment for sclerodermatous chronic graft
      versus-host disease (GVHD) due to its antifibrotic activity. Because imatinib has
      a potentially adverse effect on wound healing, the safety of its perioperative
      use in lung transplantation is unknown. Herein, we present a patient who
      underwent bilateral living-donor lobar lung transplantation for pulmonary
      complications after bone marrow transplantation, who had also received treatment
      with imatinib for sclerodermatous GVHD. Imatinib was discontinued 3 weeks before
      lung transplantation, but was resumed 1 week postoperatively for an exacerbation
      of sclerodermatous GVHD. Seven months after the postoperative the patient
      continues to do well without complications. 

PMID- 25972598
TI  - Aortic root thrombosis with coronary embolization following neo-aortic
      reconstruction in a child with hypoplastic left heart syndrome.
AB  - In the recent era, the diagnosis, treatment options, postoperative management and
      outcomes of infants born with hypoplastic left heart syndrome (HLHS) have
      undergone dramatic changes. As is the case with many other novel treatment
      modalities used for congenital heart diseases, data concerning the long-term
      outcomes and complications of the various strategies become gradually more
      available as the numbers of survivors grow. In general, complications of the
      three-stage surgical palliation used for HLHS tend to occur most commonly
      following the first-stage surgery. Post-stage 2 complications are substantially
      less common, and centre on the procedure itself and the unique physiology of the
      cavopulmonary connection. In the following case report, we describe a relatively
      rare adverse outcome that occurred following a stage 2 surgery in the form of
      native aortic root thrombosis extending to the coronary arteries. The selected
      methods of treatment used in the catheterization laboratory and later in the
      operating theatre, as well as its outcomes are described. 

PMID- 25972599
TI  - Use of patient video cases in medical education.
AB  - Patient video cases (PVCs) are brief video recordings of patients during
      spontaneous or instructed activity. PVCs are true to life and can be replayed,
      enabling the establishment of highly interactive, contextual and safe learning
      environments, with a minimum of facilitation. This article describes the use of
      workshops in which PVCs are used to assist with the development of observational
      skills and clinical reasoning in medical students and postgraduates. We describe
      why PVCs are a valuable addition to an educator's portfolio of resources, what
      evidence there is for their effectiveness, how to use videos for teaching, and
      some practical advice and tips on their collection and storage. 

PMID- 25972600
TI  - Does transport time help explain the high trauma mortality rates in rural areas?
      New and traditional predictors assessed by new and traditional statistical
      methods.
AB  - BACKGROUND: Trauma is a leading global cause of death. Trauma mortality rates are
      higher in rural areas, constituting a challenge for quality and equality in
      trauma care. The aim of the study was to explore population density and transport
      time to hospital care as possible predictors of geographical differences in
      mortality rates, and to what extent choice of statistical method might affect the
      analytical results and accompanying clinical conclusions. METHODS: Using data
      from the Norwegian Cause of Death registry, deaths from external causes 1998-2007
      were analysed. Norway consists of 434 municipalities, and municipality population
      density and travel time to hospital care were entered as predictors of
      municipality mortality rates in univariate and multiple regression models of
      increasing model complexity. We fitted linear regression models with continuous
      and categorised predictors, as well as piecewise linear and generalised additive
      models (GAMs). Models were compared using Akaike's information criterion (AIC).
      RESULTS: Population density was an independent predictor of trauma mortality
      rates, while the contribution of transport time to hospital care was highly
      dependent on choice of statistical model. A multiple GAM or piecewise linear
      model was superior, and similar, in terms of AIC. However, while transport time
      was statistically significant in multiple models with piecewise linear or
      categorised predictors, it was not in GAM or standard linear regression.
      CONCLUSIONS: Population density is an independent predictor of trauma mortality
      rates. The added explanatory value of transport time to hospital care is marginal
      and model-dependent, highlighting the importance of exploring several statistical
      models when studying complex associations in observational data.

PMID- 25972601
TI  - Effect of cellular senescence on the growth of HER2-positive breast cancers.
AB  - BACKGROUND: Oncogene-induced senescence (OIS) is a tumor suppressor mechanism.
      However, senescent cells remain viable and display a distinct secretome (also
      known as senescence-associated secretory phenotype [SASP] or senescence messaging
      secretome, [SMS]) that, paradoxically, includes protumorigenic factors. OIS can
      be triggered by ectopic overexpression of HER2, a receptor tyrosine kinase and
      the driving oncogene in a subtype of human breast cancer. However, cellular
      senescence has not been characterized in HER2-positive tumors. METHODS: Using an
      approach based on their inability to proliferate, we isolated naturally occurring
      senescent cells from a variety of tumor models including HER2-positive cells,
      transgenic mice (n = 3), and patient-derived xenografts (PDXs) (n = 6 mice per
      group from one PDX derived from one patient). Using different biochemical and
      cell biological techniques, we characterized the secretome of these senescent
      cells. All statistical tests were two-sided. RESULTS: We found that senescent
      cells arise constantly in different models of advanced breast cancers
      overexpressing HER2 and constitute approximately 5% of tumor cells. In these
      models, IL-6 and other cytokines were expressed mainly, if not exclusively, by
      the naturally occurring senescent cells (95.1% and 45.0% of HCC1954 cells and
      cells from a HER2-positive PDX expressing a senescent marker expressed IL-6,
      respectively). Furthermore, inhibition of IL-6 impaired the growth of the HER2
      positive PDX (mean tumor volume at day 101, control vs anti-huIL-6 treated,
      332.2mm(3) [95% confidence interval {CI} = 216.6 to 449.8] vs 114.4mm(3) [95% CI
      = 12.79 to 216.0], P = .005). CONCLUSIONS: Senescent cells can contribute to the
      growth of tumors by providing cytokines not expressed by proliferating cells, but
      required by these to thrive.

PMID- 25972602
TI  - Everything old is neu again: cellular senescence in HER2-positive breast cancer.

PMID- 25972603
TI  - Power and sample size estimation for epigenome-wide association scans to detect
      differential DNA methylation.
AB  - BACKGROUND: Epigenome-wide association scans (EWAS) are under way for many
      complex human traits, but EWAS power has not been fully assessed. We investigate
      power of EWAS to detect differential methylation using case-control and disease
      discordant monozygotic (MZ) twin designs with genome-wide DNA methylation arrays.
      METHODS AND RESULTS: We performed simulations to estimate power under the case
      control and discordant MZ twin EWAS study designs, under a range of epigenetic
      risk effect sizes and conditions. For example, to detect a 10% mean methylation
      difference between affected and unaffected subjects at a genome-wide significance
      threshold of P = 1 * 10-6, 98 MZ twin pairs were required to reach 80% EWAS
      power, and 112 cases and 112 controls pairs were needed in the case-control
      design. We also estimated the minimum sample size required to reach 80% EWAS
      power under both study designs. Our analyses highlighted several factors that
      significantly influenced EWAS power, including sample size, epigenetic risk
      effect size, the variance of DNA methylation at the locus of interest and the
      correlation in DNA methylation patterns within the twin sample. CONCLUSIONS: We
      provide power estimates for array-based DNA methylation EWAS under case-control
      and disease-discordant MZ twin designs, and explore multiple factors that impact
      on EWAS power. Our results can help guide EWAS experimental design and
      interpretation for future epigenetic studies.

PMID- 25972605
TI  - In this issue of Occupational Medicine.

PMID- 25972607
TI  - Edgar Degas, Repasseuses (women ironing) C.1884.

PMID- 25972606
TI  - Is the GMC guidance on confidentiality compatible with English law?

PMID- 25972604
TI  - Exosome-mediated transfer of microRNAs within the tumor microenvironment and
      neuroblastoma resistance to chemotherapy.
AB  - BACKGROUND: How exosomic microRNAs (miRNAs) contribute to the development of drug
      resistance in the context of the tumor microenvironment has not been previously
      described in neuroblastoma (NBL). METHODS: Coculture experiments were performed
      to assess exosomic transfer of miR-21 from NBL cells to human monocytes and miR
      155 from human monocytes to NBL cells. Luciferase reporter assays were performed
      to assess miR-155 targeting of TERF1 in NBL cells. Tumor growth was measured in
      NBL xenografts treated with Cisplatin and peritumoral exosomic miR-155 (n = 6
      mice per group) CD163, miR-155, and TERF1 levels were assessed in 20 NBL primary
      tissues by Human Exon Arrays and quantitative real-time polymerase chain
      reaction. Student's t test was used to evaluate the differences between treatment
      groups. All statistical tests were two-sided. RESULTS: miR-21 mean fold change
      (f.c.) was 12.08+/-0.30 (P < .001) in human monocytes treated with NBL derived
      exosomes for 48 hours, and miR-155 mean f.c. was 4.51+/-0.25 (P < .001) in NBL
      cells cocultured with human monocytes for 48 hours. TERF1 mean luciferase
      activity in miR-155 transfected NBL cells normalized to scrambled was 0.36 +/-
      0.05 (P <.001). Mean tumor volumes in Dotap-miR-155 compared with Dotap-scrambled
      were 322.80+/-120mm(3) and 76.00+/-39.3mm(3), P = .002 at day 24, respectively.
      Patients with high CD163 infiltrating NBLs had statistically significantly higher
      intratumoral levels of miR-155 (P = .04) and lower levels of TERF1 mRNA (P =
      .02). CONCLUSIONS: These data indicate a unique role of exosomic miR-21 and miR
      155 in the cross-talk between NBL cells and human monocytes in the resistance to
      chemotherapy, through a novel exosomic miR-21/TLR8-NF-kB/exosomic miR-155/TERF1
      signaling pathway.

PMID- 25972608
TI  - Occupational chronic obstructive pulmonary disease: a standard of care.
AB  - BACKGROUND: Consistent evidence from population studies report that 10-15% of the
      total burden of chronic obstructive pulmonary disease (COPD) is associated with
      workplace exposures. This proportion of COPD could be eliminated if harmful
      workplace exposures were controlled adequately. AIMS: To produce a standard of
      care for clinicians, occupational health professionals, employers and employees
      on the identification and management of occupational COPD. METHODS: A systematic
      literature review was used to identify published data on the prevention,
      identification and management of occupational COPD. Scottish Intercollegiate
      Guidance Network grading and the Royal College of General Practitioner three star
      grading system were used to grade the evidence. RESULTS: There are a number of
      specific workplace exposures that are established causes of COPD. Taking an
      occupational history in patients or workers with possible or established COPD
      will identify these. Reduction in exposure to vapours, gases, dusts and fumes at
      work is likely to be the most effective method for reducing occupational COPD.
      Identification of workers with rapidly declining lung function, irrespective of
      their specific exposure, is important. Individuals can be identified at work by
      accurate annual measures of lung function. CONCLUSIONS: Early identification of
      cases with COPD is important so that causality can be considered and action taken
      to reduce causative exposures thereby preventing further harm to the individual
      and other workers who may be similarly exposed. This can be achieved using a
      combination of a respiratory questionnaire, accurate lung function measurements
      and control of exposures in the workplace.

PMID- 25972609
TI  - Consequences of OH alert syndrome.

PMID- 25972610
TI  - Distress and job satisfaction after robbery assaults: a longitudinal study.
AB  - BACKGROUND: External/intrusive violence at work can result in psychological
      distress and can be an important risk to employee health and safety. However, the
      vast majority of workplace violence studies have employed cross-sectional and
      correlational research, designed to examine immediate reactions after being
      assaulted at work. AIMS: To explore whether exposure to robbery as a traumatic
      event may contribute to the onset of typical symptoms of psychological distress
      (anxiety depression, dysphoria and loss of confidence) and job dissatisfaction
      over time. METHODS: We collected data by using a two-wave panel design, in which
      employees working the days of bank robberies, in an Italian bank, filled in a
      questionnaire between 48h and 1 week after the robbery (T1) and 2 months after
      the robbery (T2). We performed structural equation models to evaluate the fit of
      different models to our data. RESULTS: There were 513 participants at T1 (58%
      women) and 175 (34%) participants at T2 (62% women). There was a simultaneous
      association in which psychological distress leads to job dissatisfaction both
      following robbery and 2 months later. CONCLUSIONS: Our findings support a
      synchronous effects model and suggest that interventions after suffering physical
      assaults, apart from helping employees to recover their health, should consider
      restoring their trust and confidence in the organization. This study contributes
      to understanding the dynamic relationships between a robbery at work and its
      outcomes over time, by addressing several methodological deficiencies in previous
      longitudinal studies.

PMID- 25972611
TI  - Going through the motions.

PMID- 25972612
TI  - Fashion victims campaign: responses from clothing retailers.

PMID- 25972613
TI  - The Hamilton Rating Scale for Depression.

PMID- 25972614
TI  - Fifty years ago: 'The proposed new constitution'. 1965.

PMID- 25972615
TI  - Fifty years ago: 'A poisons information service'. 1965.

PMID- 25972616
TI  - Lateral Meristems Responsible for Secondary Growth of the Monocotyledons: A
      Survey of the State of the Art.
AB  - This review highlights key historical works and the recent research on the
      monocot lateral meristems. It discusses the terminological issues (elucidating
      the terminological inconsistency found in the literature concerned), origination
      of secondary meristems, their morphology and characteristic features of the
      derivative tissues. Also the monocot cambium response to hormonal and
      gravitational stimuli is discussed. The summarized inputs in the present note are
      believed to renew interest in this field, which is important for a more
      comprehensive understanding of the abnormal secondary growth in the
      monocotyledons.

PMID- 25972617
TI  - Making Sense of the Science of Sodium.
AB  - Despite the Institute of Medicine's commitment to base its nutrient intake
      recommendations in evidence, the 2004/2005 Dietary Reference Intakes for sodium
      were not supported by evidence, as the subsequent 2013 Institute of Medicine
      review admitted. In this review, I suggest an approach to setting nutrient intake
      requirements based in physiology. Briefly, the requirement of a given nutrient
      can best be said to be the intake that calls for the least adaptation or
      compensation by the intact organism. For sodium, evidence indicates that such an
      intake is typically between 3000 and 5000 mg/d.

PMID- 25972618
TI  - Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health
      Benefits, Part 1: What to Look for and How to Recommend an Effective Fiber
      Therapy.
AB  - Dietary fiber that is intrinsic and intact in fiber-rich foods (eg, fruits,
      vegetables, legumes, whole grains) is widely recognized to have beneficial
      effects on health when consumed at recommended levels (25 g/d for adult women, 38
      g/d for adult men). Most (90%) of the US population does not consume this level
      of dietary fiber, averaging only 15 g/d. In an attempt to bridge this "fiber
      gap," many consumers are turning to fiber supplements, which are typically
      isolated from a single source. Fiber supplements cannot be presumed to provide
      the health benefits that are associated with dietary fiber from whole foods. Of
      the fiber supplements on the market today, only a minority possess the physical
      characteristics that underlie the mechanisms driving clinically meaningful health
      benefits. The first part (current issue) of this 2-part series will focus on the
      4 main characteristics of fiber supplements that drive clinical efficacy
      (solubility, degree/rate of fermentation, viscosity, and gel formation), the 4
      clinically meaningful designations that identify which health benefits are
      associated with specific fibers, and the gel-dependent mechanisms in the small
      bowel that drive specific health benefits (eg, cholesterol lowering, improved
      glycemic control). The second part (next issue) of this 2-part series will focus
      on the effects of fiber supplements in the large bowel, including the 2
      mechanisms by which fiber prevents/relieves constipation (insoluble mechanical
      irritant and soluble gel-dependent water-holding capacity), the gel-dependent
      mechanism for attenuating diarrhea and normalizing stool form in irritable bowel
      syndrome, and the combined large bowel/small bowel fiber effects for weight
      loss/maintenance. The second part will also discuss how processing for marketed
      products can attenuate efficacy, why fiber supplements can cause gastrointestinal
      symptoms, and how to avoid symptoms for better long-term compliance.

PMID- 25972619
TI  - Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health
      Benefits, Part 2: What to Look for and How to Recommend an Effective Fiber
      Therapy.
AB  - Dietary fiber that is intrinsic and intact in fiber-rich foods (eg, fruits,
      vegetables, legumes, whole grains) is widely recognized to have beneficial
      effects on health when consumed at recommended levels (25 g/d for adult women, 38
      g/d for adult men). Most (90%) of the US population does not consume this level
      of dietary fiber, averaging only 15 g/d. In an attempt to bridge this "fiber
      gap," many consumers are turning to fiber supplements, which are typically
      isolated from a single source. Fiber supplements cannot be presumed to provide
      the health benefits that are associated with dietary fiber from whole foods. Of
      the fiber supplements on the market today, only a minority possess the physical
      characteristics that underlie the mechanisms driving clinically meaningful health
      benefits. In this 2-part series, the first part (previous issue) described the 4
      main characteristics of fiber supplements that drive clinical efficacy
      (solubility, degree/rate of fermentation, viscosity, and gel formation), the 4
      clinically meaningful designations that identify which health benefits are
      associated with specific fibers, and the gel-dependent mechanisms in the small
      bowel that drive specific health benefits (eg, cholesterol lowering, improved
      glycemic control). The second part (current issue) of this 2-part series will
      focus on the effects of fiber supplements in the large bowel, including the 2
      mechanisms by which fiber prevents/relieves constipation (insoluble mechanical
      irritant and soluble gel-dependent water-holding capacity), the gel-dependent
      mechanism for attenuating diarrhea and normalizing stool form in irritable bowel
      syndrome, and the combined large bowel/small bowel fiber effects for weight
      loss/maintenance. The second part will also discuss how processing for marketed
      products can attenuate efficacy, why fiber supplements can cause gastrointestinal
      symptoms, and how to avoid symptoms for better long-term compliance.

PMID- 25972620
TI  - Teenage Cohabitation, Marriage, and Childbearing.
AB  - Cohabitation is an integral part of family research; however, little work
      examines cohabitation among teenagers or links between cohabitation and teenage
      childbearing. Drawing on the National Survey of Family Growth (2006-10), we
      examine family formation activities (i.e., cohabitation, marriage, and
      childbearing) of 3,945 15-19 year old women from the mid 1990s through 2010. One
      third (34%) of teenagers cohabit, marry, or have a child. Teenage cohabitation
      and marriage are both positively associated with higher odds of having a child.
      The vast majority of single pregnant teenagers do not form a union before the
      birth of their child; only 22% cohabit and 5% marry. Yet most single pregnant
      teenagers eventually cohabit, 59% did so by the child's third birthday and about
      9% marry. Cohabitation is an important part of the landscape of the adolescent
      years, and many teenage mothers described as "single mothers" are actually in
      cohabiting relationships.

PMID- 25972621
TI  - Social Science and Neuroscience beyond Interdisciplinarity: Experimental
      Entanglements.
AB  - This article is an account of the dynamics of interaction across the social
      sciences and neurosciences. Against an arid rhetoric of 'interdisciplinarity', it
      calls for a more expansive imaginary of what experiment - as practice and ethos -
      might offer in this space. Arguing that opportunities for collaboration between
      social scientists and neuroscientists need to be taken seriously, the article
      situates itself against existing conceptualizations of these dynamics, grouping
      them under three rubrics: 'critique', 'ebullience' and 'interaction'. Despite
      their differences, each insists on a distinction between sociocultural and
      neurobiological knowledge, or does not show how a more entangled field might be
      realized. The article links this absence to the 'regime of the inter-', an ethic
      of interdisciplinarity that guides interaction between disciplines on the
      understanding of their pre-existing separateness. The argument of the paper is
      thus twofold: (1) that, contra the 'regime of the inter-', it is no longer
      practicable to maintain a hygienic separation between sociocultural webs and
      neurobiological architecture; (2) that the cognitive neuroscientific experiment,
      as a space of epistemological and ontological excess, offers an opportunity to
      researchers, from all disciplines, to explore and register this realization.

PMID- 25972622
TI  - Macrophage migration inhibitory factor promoter polymorphisms (-794 CATT 5-8 and 
      173 G>C): relationship with mRNA expression and soluble MIF levels in young obese
      subjects.
AB  - We analyzed the relationship of -794 CATT5-8 and -173 G>C MIF polymorphisms with
      mRNA and soluble MIF in young obese subjects. A total of 250 young subjects, 150
      normal-weight and 100 obese subjects, were recruited in the study. Genotyping of 
      794 CATT5-8 and -173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP,
      respectively. MIF mRNA expression was determined by real-time PCR and serum MIF
      levels were measured using an ELISA kit. For both MIF promoter polymorphisms, no
      significant differences in the genotype and allele frequencies between groups
      were observed. MIF mRNA expression was slightly higher in obese subjects than in
      normal-weight subjects (1.38-fold), while soluble MIF levels did not show
      differences between groups. In addition, we found an increase in MIF mRNA
      expression in carriers of the 6,6 and C/C genotypes and the 6G haplotype of the 
      794 CATT5-8 and -173 G>C MIF polymorphisms, although it was not significant. In
      conclusion, this study found no relationship between obesity and MIF gene
      promoter polymorphisms with MIF mRNA expression in young obese subjects. 

PMID- 25972623
TI  - First-trimester uterine artery Doppler analysis in the prediction of later
      pregnancy complications.
AB  - Uterine artery Doppler waveform analysis has been extensively studied in the
      second trimester of pregnancy as a predictive marker for the later development of
      preeclampsia and fetal growth restriction. The use of Doppler interrogation of
      this vessel in the first trimester has gained momentum in recent years. Various
      measurement techniques and impedance indices have been used to evaluate the
      relationship between uterine artery Doppler velocimetry and adverse pregnancy
      outcomes. Overall, first-trimester Doppler interrogation of the uterine artery
      performs better in the prediction of early-onset than late-onset preeclampsia. As
      an isolated marker of future disease, its sensitivity in predicting preeclampsia
      and fetal growth restriction in low risk pregnant women is moderate, at 40-70%.
      Multiparametric predictive models, combining first-trimester uterine artery
      pulsatility index with maternal characteristics and biochemical markers, can
      achieve a detection rate for early-onset preeclampsia of over 90%. The ideal
      combination of these tests and validation of them in various patient populations
      will be the focus of future research. 

PMID- 25972625
TI  - Ileocolic Intussusception Caused by a Giant Ulcerating Lipoma of Bauhin's Valve:
      an Unusual Cause of Intestinal Obstruction in the Adult.
AB  - We report a case of intestinal obstruction in a 73-year-old woman caused by
      ileocolic intussusception. The underlying cause was a giant submucosal ulcerating
      lipoma (6 * 3.3 * 3.8 cm) extending from the superior mucosal lip of Bauhin's
      valve. Abdominal ultrasonography showed a pathognomonic target-like mass
      appearing as multiple concentric rings. CT scan confirmed the diagnosis. Because
      of apparent obstruction, a laparotomy with right hemicolectomy and ileocolic
      anastomosis was performed. Lipomas most frequently occur in the cecum and
      ascending colon where they represent the most common submucosal mesenchymal
      tumor. They typically occur in elderly women with an incidence that varies from
      0.15 to 0.56 %. Pain, rectal bleeding, and obstruction are typical symptoms. When
      faced with an intussusception in children, reduction with air per rectum can be
      performed. In adults, however, malignant cell spreading and seeding is of big
      concern. Since approximately 20-50 % of all underlying causes are malignant,
      explorative surgery is favored in adults. 

PMID- 25972624
TI  - Repetitive hyperbaric oxygenation attenuates reactive astrogliosis and suppresses
      expression of inflammatory mediators in the rat model of brain injury.
AB  - The exact mechanisms by which treatment with hyperbaric oxygen (HBOT) exerts its
      beneficial effects on recovery after brain injury are still unrevealed.
      Therefore, in this study we investigated the influence of repetitive HBOT on the
      reactive astrogliosis and expression of mediators of inflammation after cortical
      stab injury (CSI). CSI was performed on male Wistar rats, divided into control,
      sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows:
      10 minutes of slow compression, 2.5 atmospheres absolute (ATA) for 60 minutes,
      and 10 minutes of slow decompression, once a day for 10 consecutive days. Data
      obtained using real-time polymerase chain reaction, Western blot, and
      immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT
      applied after the CSI attenuates reactive astrogliosis and glial scarring, and
      reduces expression of GFAP (glial fibrillary acidic protein), vimentin, and ICAM
      1 (intercellular adhesion molecule-1) both at gene and tissue levels. In
      addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia,
      neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive
      HBOT, by prevention of glial scarring and limiting of expression of inflammatory
      mediators, supports formation of more permissive environment for repair and
      regeneration. 

PMID- 25972626
TI  - Incidentally found retroperitoneal ganglioneuroma in an adult.
AB  - The ganglioneuroma is a very rare tumor arising from sympathetic nerve system. An
      asymptomatic retroperitoneal ganglioneuroma was found incidentally in a 35-year
      old woman. Ultrasonography, computed tomography, and magnetic resonance imaging
      showed a retroperitoneal mass extending to the left adrenal gland, and
      surrounding abdominal aorta, celiac axis, left renal and adrenal arteries, and
      veins. The tumor was resected and histologic examination showed ganglioneuroma. 

PMID- 25972627
TI  - Synchronous primary malignancies in breast and kidney: a rare case report.
AB  - Multiple synchronous malignancies are rarer than metachronous ones. Primary
      synchronous breast and renal cancer is even rare. Such a case requires strict
      exclusion of possible metastasis to either site and to confirm the primary nature
      of each malignancy for better outcome of management and survival benefit.
      Multiple primary synchronous malignancies may be due to shared genetic mutations
      if any common carcinogenic factor cannot be found. The role of estrogens in cases
      in which human renal carcinoma is associated with other primary tumours involving
      steroid-hormone target tissues, is tentative and can only be hypothesised due to
      paucity of such data in literature. One should consider the possibility of
      concomitant dual or multiple primary tumours in a patient presented with mass
      lesions at various sites, especially if one of the sites is the kidney. We
      present a case report of a patient with synchronous primary breast and renal
      cancer. 

PMID- 25972628
TI  - Infective gangrene in extremity trauma-are we targeting the right organisms?
AB  - Mucormycosis is a rare and fatal infection that is known to occur in
      immunocompromised and diabetic patients. The infection is caused by a fungus of
      the class Zygomycetes. It has been associated with open fractures in patients at
      risk. We report a case of cutaneous mucormycosis leading to gangrene after a
      closed fracture. We recommend considering mucormycosis as a differential for
      wound infections not responding to antibiotics, even in closed injuries. Tissue
      from surgical debridement should be sent for histopathological and
      microbiological examination to diagnose the condition early. Early recognition,
      surgical management, and parenteral antifungal therapy are the mainstay of
      management of this illness. 

PMID- 25972629
TI  - Limb saving procedure in metastatic leiomyosarcoma of the femoral vein: case
      report and literature review.
AB  - Primary venous leiomyosarcoma is very rare and first description was made by Perl
      in 1871. Most cases are from venous system and half of them are reported to
      originate in inferior vena cava. We report the case of a 77-year-old Caucasian
      man with a leiomyosarcoma of the femoral vein. A leg preservation surgery was
      decided. Eight months later, the patient died of tumor progression. A PubMed
      search using the terms "leiomyosarcoma femoral vein" and "leiomyosarcoma vein"
      was performed. All cases of composite iliac-femoral leiomyosarcoma were excluded,
      and as far as possible, only well-documented cases were included. Median age was
      55 years, seven men and six women, tumor resection was performed by six authors,
      six others performed a vascular resection, and one preferred for a thigh
      excision. Prognosis remains poor if metastasis is present, and in these cases, a
      conservative surgery is recommended to preserve patients' quality of life. 

PMID- 25972630
TI  - Primary appendiceal adenocarcinoma masquerading as primary bladder tumor: a case
      report and review of literatures.
AB  - Adenocarcinoma of the appendix invading the urinary bladder is very rare. We
      describe such a case in a 42-year-old man and review the relevant literatures. In
      the present case, although ultrasonography and computed tomography scan revealed
      a mass in the bladder or in the pelvic and biopsies by cystoscopy showed an
      adenocarcinoma suspicious for primary of the bladder, its real origin was hard to
      distinguish. An open exploratory surgery was performed with subsequent resection
      of appendix and partial bladder. Postoperative histopathological examinations
      revealed the appendiceal adenocarcinoma infiltrating the bladder wall. The
      patient refused the right hemicolectomy and received 3 cycles of adjuvant
      radiotherapy. However, tumor recurrence was found in the bladder 6 months after
      surgery, and radical cystectomy was eventually performed. 

PMID- 25972631
TI  - Epidermoid cyst-a rare mediastinal mass.
AB  - A 39-year-old male was referred to our service for treatment of an asymptomatic
      mediastinal mass. The mass was detected on a routine pre-employment chest X-ray.
      CT scan showed a well-defined soft tissue mass measuring 7.5 * 5.5 * 5.3 cm in
      close relation to the right border of the heart. A CT-guided biopsy proved to be
      inconclusive as necrotic tissue was obtained. At exploratory thoracotomy, a well
      defined cyst was found attached to the right side of the pericardium. The cyst
      was totally excised and sent for histopathological examination which came back
      with a surprise diagnosis of epidermoid cyst. 

PMID- 25972632
TI  - Acute small intestinal obstruction-an unusual complication of capsule endoscopy.
AB  - We report a case of endoscopic capsule impaction causing acute small intestinal
      obstruction in a patient with Crohn's disease (CD), having obscure
      gastrointestinal bleeding. A 57-year old female presented with features of acute
      small bowel obstruction 2 days after capsule endoscopy elsewhere for the
      evaluation of intermittent bleeding per rectum and iron deficiency anemia.
      Patient underwent an exploratory laparotomy with right hemicolectomy for the
      diseased ileocecal region which mimicked malignancy. The capsule was found to be
      impacted in the strictured lumen of the terminal ileum. Post operative
      histopathological examination revealed it to be Crohn's disease. 

PMID- 25972633
TI  - Adenocarcinoma in Choledochal Cyst-a Case Report.

PMID- 25972634
TI  - Single-incision laparoscopic surgery for colon cancer in patient with situs
      inversus totalis: report of a case.
AB  - A preliminary experience with single-incision laparoscopic colectomy for colon
      cancer with situs inversus totalis (SIT) is reported. An 87-year-old man was
      admitted because of a fecal occult blood. A colonoscopy revealed cecal cancer. An
      air-barium and a computed tomography contrast enema showed the right-sided
      descending colon and the left-sided ascending colon and cecum. The surgical
      procedures were as follows: First, a Lap protector was inserted through a 2.5-cm
      transumbilical incision. Three 5-mm ports were placed in the Lap protector. We
      successfully performed ileocolectomy with lymph node dissection by using a single
      incision laparoscopic approach without any technical problems. The operative time
      was 125 min, and blood loss was negligible. Postoperative follow-up did not
      reveal any umbilical wound complications and recurrences. 

PMID- 25972635
TI  - Transitional cell carcinoma of ureter simulating left colonic malignancy-a rare
      case.
AB  - We reported a case of ureteric tumor, an uncommon disease presenting with colonic
      obstruction. This 52-year-old lady presented with history of colicky pain left
      lower abdomen for 5 months. Colonoscopy revealed circumferential nonnegotiable
      stricture at 25 cm from anal verge, and colonoscopic biopsy was inconclusive.
      Contrast-enhanced computed tomography (CECT) showed a growth involving sigmoid
      colon and left ureter with proximal left hydroureteronephrosis with
      nonfunctioning left kidney. Guided fine needle aspiration cytology (FNAC) showed
      features of an adenocarcinoma. The patient was operated with a diagnosis of
      carcinoma colon and underwent low anterior resection with left
      nephroureterectomy. Histopathology of resected specimen revealed ureteric
      transitional cell carcinoma with colon infiltration. She had smooth postoperative
      recovery. 

PMID- 25972636
TI  - Ampullary carcinoma in a patient with agenesis of the dorsal pancreas: a case
      report.
AB  - The most common congenital anomaly of the pancreas is pancreatic divisum
      (Tadokoro et al. in Anat Res Int 2011:1-7, 2011). Agenesis of the dorsal pancreas
      is extremely rare (Schnedl et al. in World J Gastroenterol 15(3):376-377, 2009).
      We are reporting a case of agenesis of dorsal pancreas presented with ampullary
      carcinoma. 

PMID- 25972637
TI  - Spigelian hernia: a diagnostic dilemma and laparoscopic management.
AB  - Spigelian hernias, also called as lateral ventral hernias, are rare hernias to
      present themselves in clinical practice. The significance of these hernias lies
      in the fact that they are commonly intraparietal hernias and are, hence,
      difficult to diagnose clinically. Moreover, the neck of these hernias is usually
      small, posing a fair risk of strangulation. With the advancement in laparoscopic
      hernia repair, there is evidence that Spigelian hernias too can be repaired
      laparoscopically, thereby causing less morbidity and shorter hospital stay. Here,
      we present a rare case of large Spigelian hernia that posed to us as a diagnostic
      dilemma. The symptoms, clinical findings, and ultrasound of the patient were not
      specific, and a CT scan had to be used as the measure to confirm the diagnosis.
      The patient was then managed successfully with laparoscopic intraperitoneal onlay
      mesh repair. The details of the case and a brief discussion are included. 

PMID- 25972638
TI  - New variation of right recurrent laryngeal nerve: cases report.
AB  - The recognition of variation in recurrent laryngeal nerves is important for both
      surgeons and the prognosis of patients undergoing surgery of the neck. Here, we
      reported a new variation of the right recurrent laryngeal nerves in five patients
      with thyroid surgery. The new variation is characterized by the additional
      ascending intracranial branches after division of laryngeal branches. 

PMID- 25972639
TI  - Hypergiant hepatic hemangiomas: case series.
AB  - Hemangiomas are the most common benign tumors of the liver. Hepatic hemangiomas
      originate from the proliferation of vascular endothelial cells, and enlarge by
      ectasia rather than hyperplasia. They are very variable in size and are
      classified accordingly and their management in the larger variety is debatable.
      Hypergiant hepatic hemangiomas are defined as those which are more than 10 cm in
      size. These are fairly uncommon in clinical practice. The treatment spectrum
      varies from masterly inactivity to resection depending upon a number of factors.
      We report a series of 10 cases of hyper giant hepatic hemangiomas studied and
      reviewed over a period of 5 years. These were evaluated with respect to their
      age, gender, clinical presentation, investigation findings, treatment offered,
      and final outcome. Five were treated with resection, four with enucleation, and
      one was kept under observation. All operated patients had an uneventful post
      operative recovery and the one managed conservatively was asymptomatic on follow
      up. 

PMID- 25972640
TI  - Bamboo in the Brain-an Unusual Mode of Injury.
AB  - A 22-year-old male presented with a history of penetration of bamboo over the
      head which had fallen from the height of 40 ft. The position of the object was
      confirmed by computed tomography and patient underwent surgery immediately with
      removal of the object. The patient did well after surgery. Different modes of
      penetrating injury to the brain by bamboo and wooden objects, complications and
      management issues are discussed with a brief review of literature. 

PMID- 25972641
TI  - Favorable outcome of cerebral fat embolism syndrome with a glasgow coma scale of
      3: a case report and review of the literature.
AB  - Prognosis of deep coma caused by cerebral fat embolism syndrome (CFES) is rarely
      reported. We present a case of fulminant CFES which was induced by long bone
      fracture, with a Glasgow Coma Scale (GCS) of 3/15. The brain magnetic resonance
      imaging (MRI) revealed abnormal spotty lesions scattered over both cerebral
      hemispheres and the posterior fossa. Thirty days later, the patient regained
      consciousness with a GCS of 15/15. 

PMID- 25972642
TI  - Langerhans cell histiocytosis of thyroid-a diagnostic dilemma.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease of antigen presenting cells
      and involvement of thyroid is really uncommon. The thyroid if involved is usually
      seen in multisystem disease but isolated thyroid involvement is very rare. The
      diagnosis of Langerhans cell histiocytosis of the thyroid is very challenging due
      to its rarity and is usually misdiagnosed as benign goiters, undifferentiated
      carcinoma, lymphoma, etc. Management of Langerhans cell histiocytosis of the
      thyroid also remains controversial. Prognosis in an isolated Langerhans cell
      histiocytosis of the thyroid is usually good but as it may precede a multisystem
      involvement, prolonged follow-up is required. We present a rare case of
      Langerhans cell histiocytosis of the thyroid, with variable diagnoses on fine
      needle aspiration cytology. 

PMID- 25972643
TI  - Foregut duplication cyst associated with esophageal atresia-one-stage neonatal
      surgical repair.
AB  - Foregut duplication cysts can occur anywhere along the foregut-derived
      structures. Its association with esophageal atresia (EA) and tracheoesophageal
      fistula (TEF) is exceptionally rare, the majority of cases being diagnosed at an
      older age due to symptoms or complications. We present the third reported case in
      the literature, when diagnosis and treatment were done at the time of repair for
      EA-TEF. 

PMID- 25972644
TI  - Individualized treatment for the mandibular segmental defect: a case report.
AB  - Ameloblastomas are slowly growing, locally invasive tumors with high recurrence
      rate and more common in the mandible, if not treated they can grow to enormous
      size. Radical resection is the only predictable form of treatment for
      ameloblastomas. However, mandibular resection can lead to dysfunctions in
      appearance, speech, mastication, and deglutition, which severely impair the
      patients' quality of life. The reconstruction of extensive bone defects in the
      maxillofacial area is still challenging. To meet the demands of functional
      reconstruction, minimizing the negative influence of mandibular malformation, and
      disability on patients, the individualized systematic treatment plans highlight
      denture prosthodontics and require much consideration of multidisciplinary
      cooperation, with such related fields as maxillofacial surgery, oral
      implantology, prosthodontics, and radiology taken into account. In this report,
      we will present a case of reconstructing the mandibular segmental defect after
      the resection of a rarely giant ameloblastoma. In the case, we took the
      restoration of the missing teeth and the rehabilitation of the masticatory
      function as well as restoring bony continuities and facial appearance into
      consideration, communicated well with prosthodontists and implantologists before
      surgery, making the individualized systematic treatment plan more effective and
      efficient. 

PMID- 25972645
TI  - Cutaneous metastasis of renal cell carcinoma masquerading as scrotal growth.
AB  - Cutaneous metastases are an uncommon manifestation of visceral malignancy. We
      report a case of a 56-year-old male who presented with an ulcerated scrotal mass
      and inguinal swelling on the left side. Fine needle aspiration from both the
      sites revealed deposits of renal cell carcinoma though the patient had no
      urologic symptoms. Subsequent work-up revealed a renal mass. This case emphasizes
      the importance of keeping renal cell carcinoma as differential in cases who
      present with cutaneous metastases. 

PMID- 25972646
TI  - Laparoscopic Approach to Type IV Sacrococcygeal Teratoma in an Adult.
AB  - Presacral teratoma is extremely rare in adults. A 35-year-old lady was diagnosed
      with presacral teratoma on MRI abdomen and pelvis. The tumour was enucleated
      laparoscopically, this being the first such case to be reported in India and
      fifth case in world literature. Though traditionally, anterior approach of the
      presacral tumours meant laparotomy, but recently, laparoscopy has been reported
      as a safe and effective option for these tumours with the advantages of a
      magnified view in the narrow pelvis, easier development of natural planes by
      pneumoperitoneum, faster recovery and less complications if expertise is
      available. 

PMID- 25972647
TI  - Torsion of a Giant Intra-abdominal Testicular Seminoma Presenting as Acute
      Abdomen.
AB  - Intra-abdominal neoplastic testicular torsion is a very rare clinical condition,
      which is normally not considered during differential diagnosis of acute abdomen.
      In any male patient with acute abdominal symptoms and absence of scrotal testis,
      a high index of suspicion for intra-abdominal testicular torsion should be
      maintained. An increased diagnostic yield is dependent on an expedient and
      comprehensive preoperative evaluation. An illustrated case report is presented. 

PMID- 25972648
TI  - Gastric Gangrene Due to a Strangulated Paraesophageal Hernia-a Case report.
AB  - Paraesophageal hernias are considered to be benign entities which are usually
      managed conservatively. We present a case of a middle-aged male with no previous
      history of esophageal hernia who presented with acute chest and abdominal pain.
      The patient was diagnosed to have a type 2 paraesophageal hernia with gastro
      thorax. Laparotomy was performed during which it was found that herniated segment
      of the stomach had strangulated and gangrenous. Thoracotomy was performed and
      gangrenous stomach segment resected. A roux-en-Y esophago-jejunostomy was
      performed. Diaphragmatic defect was plicated. Patient recovered with adequate
      post operative support. A review of the literature revealed that paraesophageal
      hernias presenting as acute abdominal pain is a rare clinical entity and those
      with gastric gangrene is even rarer, with high mortality rates. We suggest that
      paraesophageal hernias require to be managed actively considering the seriousness
      of potential complications and the relative safety of newer elective surgical
      modalities. A high index of suspicion is needed in order to avoid missing this
      diagnosis in patients presenting with chest pain. 

PMID- 25972649
TI  - Removal of a Giant Rectosigmoid Phytobezoar without Laparotomy.
AB  - Bezoars are the uncommon result of ingestion of indigestible or poorly digestible
      substances. Phytobezoars are the most common bezoars in children. Small bowel
      obstruction, especially of the terminal ileum, is the most common complication.
      Colonic obstruction is rare. Most reviewed intestinal phytobezoars with
      obstruction necessitate laparotomy with enterotomy. Here, we report a rare case
      of giant rectosigmoid phytobezoar with near-total colonic obstruction.
      Successfully, removal of this bezoar by an alternative way of fragmentation with
      colonoscopy, not conventional enterotomy is needed. The patient recovered well
      and then discharged without any morbidity 2 days later. 

PMID- 25972650
TI  - A case of vascular malformation of the neck.
AB  - Vascular malformations are rare congenital vascular anomalies composed of
      inappropriately connected vasculature. They are usually present at birth, are
      progressive, infiltrative and require intervention. Vascular malformations need
      to be differentiated from haemangiomas which are congenital vascular neoplasms.
      We present a case of vascular malformation in a 6-year old child who presented
      with a progressive swelling in the neck and was treated by surgical excision.
      This case is being presented because of its peculiar clinical presentation. 

PMID- 25972651
TI  - Intracranial metastasis of adenocarcinoma of the prostate presenting with
      symptoms of spinal cord compression.
AB  - Spinal cord compression is a not uncommon complication of metastatic prostate
      cancer. Intracranial metastasis of prostatic adenocarcinoma is however unusual.
      We report a case of a 67-year-old man with metastatic prostate carcinoma, who
      presented with a 3-day history of lower limb weakness and collapse. Neurological
      assessment demonstrated increased tone and reduced power in both legs. As he had
      typical signs and symptoms of spinal cord compression, an MRI of the spine was
      performed; this demonstrated no evidence of cord compression. A subsequent CT of
      the brain demonstrated an extensive parafalcine metastasis. This revealed an
      extensive enhancing mass extending bilaterally along almost the entire length of
      the falx cerebri, measuring up to 3 cm in width and associated with marked white
      matter oedema in the adjacent brain bilaterally. Unfortunately, this man
      succumbed to his illness a few days later. The imaging findings are presented and
      highlight the importance of brain imaging in patients presenting with suspected
      cord compression due to prostatic metastatic disease when MR of the spine shows
      no evidence of cord compression. 

PMID- 25972652
TI  - A rare case of large jejunal diverticulum presenting as intestinal obstruction
      due to small bowel volvulus.
AB  - Jejunal diverticula are quite rare. Furthermore, small bowel diverticular disease
      resulting in volvulus can lead to complications necessitating surgical
      intervention. In this manuscript, we report a case of large sacculated jejunal
      diverticulum causing small bowel volvulus in a 40-year male. The jejunal
      mesentery at the base of the diverticulum was adhered to the terminal ileal
      mesentery forming a narrow base and complete small bowel going into volvulus by
      rotating around the narrow base. This case highlights a large jejunal
      diverticulum causing small bowel volvulus as an uncommon mechanism of complete
      small bowel volvulus. Although a rare entity, familiarity with jejunal
      diverticular disease, its complications and its management should be part of
      every surgeon's base of knowledge when considering abdominal pathology. 

PMID- 25972653
TI  - A Rare Case of Richter's Variety of Obstructed Femoral Hernia in a Male.
AB  - Femoral hernias are elusive conditions that, despite having life-threatening
      complications, are often undiagnosed in asymptomatic patients. They are less
      common than inguinal hernias and occur more frequently in females [Purushotham et
      al. (2014) J Evol Med Dent Sci 3(05):1160-1163]. In the first place, femoral
      hernia in a male patient is itself, a very rare clinical presentation, let alone
      complications like obstruction or strangulation in the second place. Thus,
      despite the fact that femoral hernias account for only 2-4 % of all groin
      hernias, their timely and correct diagnosis is vital due to the increased
      mortality associated with emergency surgery for their complications [Arkoulis et
      al. (2012) Ox J Med, J Surg Case Rep 2012(6):6]. This, however, is not always
      easy, where mortality has been found to be tenfold. Here, we present a case of
      right-sided obstructed femoral hernia of Richter's variety in a male of 52 years
      of age. 

PMID- 25972654
TI  - Radionecrosis 30 years after breast cancer.
AB  - This report describes the case of a 70-year-old woman presenting to outpatient
      with a several-week history of a painful mass in her right breast, 30 years after
      her treatment for primary breast cancer. At first, this was suspected to have
      been a recurrence of her malignancy; however, repeated biopsies ultimately proved
      this to be negative. Her injury was actually a case of radiotherapy-induced
      necrosis (radionecrosis) and was subsequently treated with surgical debridement. 

PMID- 25972655
TI  - Idiopathic inferior mesenteric arteriovenous fistula: a rare cause of pulsatile
      abdominal mass.
AB  - Inferior mesenteric arteriovenous fistula (AVF) is an extremely rare vascular
      abnormality which may be idiopathic or secondary to previous trauma or surgery,
      and it may result in portal hypertension or ischemic colitis if left untreated.
      Imaging can help accurately diagnose visceral AVFs and create a vascular map to
      display the feeding artery and draining vein before the surgery; however,
      multidetector computed tomography (MDCT) angiography of inferior mesenteric AVF
      is not well documented in the literature. In this article, the authors report a
      case of inferior mesenteric AVF in a 48-year-old woman evaluated for left-sided
      abdominal pain and diagnosed preoperatively by MDCT angiography. Surgical
      excision of the AVF was successfully performed, and the postoperative course was
      uneventful. 

PMID- 25972657
TI  - Parasitic twin with gastroschisis is one of the rarest variant of conjoined
      twins: a case report.
AB  - We report a case of parasitic twin or incomplete or heteropagus twining of extra
      portions of a pelvis, lower and upper limbs, duplication of genitalia and
      herniation of intestinal tract with spleen-variant of conjoined twinning (CT)
      consistent with fusion of two embryos followed by resorption of the caudal half
      of one of them, resulting in a normal male baby with the upper half of a male
      parasitic twin fused to his chest. 

PMID- 25972656
TI  - Invasive Gastric Mucormycosis-a Case Report.
AB  - Mucormycosis is an opportunistic fungal infection that is associated with high
      mortality in immunocompromised individuals. While rhinocerebral and pulmonary
      forms are most common, primary gastrointestinal mucormycosis is very uncommon.
      The stomach is the most commonly affected organ followed by the colon and ileum
      in alimentary zygomycosis. We report a rare case of invasive gastric mucormycosis
      in a 50-year-old diabetic gentleman with a history of chronic alcoholism
      presenting with complaints of pain and distension of the abdomen for 6 days
      associated with fever, nausea, vomiting and anorexia. At presentation, he was
      hemodynamically unstable, febrile with uncontrolled blood sugar level and had
      negative HIV serology. There was generalized guarding, rigidity and distension of
      the abdomen and investigations confirmed perforative peritonitis. Upon
      exploration, there was solitary large 4 * 4 cm size perforated ulcer in the
      gastric body with greenish, greyish sloughed out mucosa within. Wedge resection
      of the ulcer with primary closure was performed. Histopathology revealed
      aseptate, broad, obtuse angled fungal hyphae, and invasive mucormycosis was
      confirmed by special stains like Periodic acid-Schiff (PAS) and Gomori's
      methenamine silver (GMS). Very few cases of invasive gastric mucormycosis
      associated with uncontrolled diabetes and alcoholism have been reported in the
      literature. Delayed presentation of the patient along with rapid progression to
      fungal septicaemia resulted in the case fatality despite early surgical
      intervention and critical care management. 

PMID- 25972658
TI  - Inadvertent ligation of the main pancreatic duct: an extremely rare complication
      of choledochal cyst excision.
AB  - Pancreatic ductal injury is rare during choledochal cyst excision. Most cases
      present in the immediate postoperative period with pancreatic fistula or acute
      pancreatitis are managed conservatively. But, inadvertent ligation of the main
      pancreatic duct with subsequent recurrent pancreatitis and upstream dilatation of
      the pancreatic duct requiring a pancreatic ductal drainage operation has not been
      reported in the English literature. A 23-year-old female patient presented with
      recurrent episodes of upper abdominal pain for about 16 months. She had a history
      of type-1 choledochal cyst excision 18 months back. She was evaluated with
      abdominal ultrasound and magnetic resonance cholangiopancreatography (MRCP). MRCP
      showed hugely dilated main pancreatic duct with normal hepaticojejunostomy
      anastomosis. There was no residual cyst. MRCP findings were suggestive of
      stricture of the main pancreatic duct due to previous surgery. Endoscopic
      pancreatic ductal decompression failed. The patient was treated successfully with
      pancreaticogastrostomy. Postoperative recovery was uneventful. The patient was
      well at 24-month follow-up. 

PMID- 25972659
TI  - Mechanical bowel obstruction due to localized extensive amyloidotic involvement
      in the left colon.
AB  - Amyloidosis is a disorder caused by extracellular deposition of insoluble protein
      fibrils in various tissues. Colonic amyloidosis is a rare clinical manifestation
      which can mimic tumor, inflammatory bowel disease, or ischemic colitis. The most
      common symptoms of colonic amyloidosis include bleeding, ulceration, diarrhea,
      and abdominal pain. However, colonic obstruction due to extensive submucosal
      amyloidosis is extremely rare. Considering the wide variety of symptoms and
      potentially effected organs, the diagnosis can be challenging particularly in
      emergent conditions. In this paper, a case with mechanic bowel obstruction due to
      extensive amyloidotic involvement of the left colon is presented. 

PMID- 25972660
TI  - Intravesical migration of intrauterine device mimicking bladder stone on
      radiologic imaging: a case report.
AB  - Due to its high cost-effectiveness, intrauterine device (IUD) is one of the
      widely used contraception methods worldwide. Intravesical migration of an IUD via
      perforation of the uterus and bladder is very rare. Endoscopic approach is
      recommended in the treatment, but open surgery may also be needed rarely. In this
      report, we present the case of a 37-year-old female who was misdiagnosed
      radiologically with bladder stone, but later on, it was understood that an IUD
      migrated to the bladder and resulted in stone formation. Laser lithotripsy was
      performed, and the migrated IUD was unearthed. Removal of the IUD with
      cystoscopic forceps was unsuccessful. Postoperative pelvic computed tomography
      revealed that a part of the IUD was outside the bladder. At the next operation
      session, laparoscopic removal of the IUD was applied. The patient was followed up
      for 5 days with a Foley catheter and discharged after performing cystography,
      assuring us that the bladder contours were normal. 

PMID- 25972661
TI  - Peutz-jeghers syndrome with synchronous adenocarcinoma arising from ileal polyps.
AB  - Peutz-Jeghers syndrome is a rare inherited autosomal disease characterized by
      mucocutaneous pigmentation and multiple polyps in the gastrointestinal tract. The
      clinical picture is characterized by repeated episodes of polyp-induced
      intestinal obstruction, abdominal pain, and bleeding per rectum. Predisposition
      to both gastrointestinal and nongastrointestinal malignancies is increased in a
      patient with Peutz-Jeghers syndrome. This is a case report of a 29-year-old male
      with Peutz-Jeghers syndrome who presented with a complaint of recurrent abdominal
      pain. CT scan revealed a single obstructing ileal polyp. However, preoperatively,
      another large ileal polyp with multiple small jejunal polyps was seen.
      Histopathology of both ileal polyps was identified as a mucinous adenocarcinoma
      infiltrating up to the serosa. The follow-up endoscopies showed small multiple
      polyps in the stomach, duodenum, and colon. Histopathology of all endoscopically
      removed polyps was consistent with the diagnosis of hamartomatous polyps. Very
      few cases of intestinal intussusception combined with synchronous malignant small
      intestine polyps have been reported until to date. 

PMID- 25972662
TI  - Prosthetic left renocaval bypass for posterior nutcracker syndrome.
AB  - A 58-year-old man presented with severe hematuria of unknown origin and
      intermittent left flank pain for 8 months, and he was diagnosed with posterior
      nutcracker syndrome. He underwent prosthetic left renocaval bypass with complete
      resolution of symptoms. Computed tomography showed a functional graft between the
      left renal vein and caval vein. This technique is a feasible choice for surgical
      treatment of posterior nutcracker syndrome with satisfactory results. 

PMID- 25972663
TI  - Multiple impacted urethral metallic needles and screws (foreign bodies)
      associated with polyembolokoilamania.
AB  - This study aims to present the challenges faced in the management of multiple
      impacted foreign bodies, needles, and screws from the penile and bulbar urethra.
      A young man presented with complaint of a hard perineal swelling and passage of
      metallic nails per urethra. Pelvic radiograph revealed multiple foreign bodies
      (nails) in the penile and bulbar urethra. Successful cystoscopic removal of 11
      foreign bodies comprising four large metallic screws and seven nail-like large
      sewing needles was done in two sessions. The most prevalent motivation for self
      insertion of urethral foreign bodies is autoerotism/psychological impairment.
      Appropriate surgical technique guided by physical examination/ imaging with
      endoscopic removal is often successful, depending on the object's physical
      attributes and morphology while minimizing urothelial trauma and preserving
      voiding and erectile function. Follow-up cystourethroscopy is important for
      diagnosing any complications and urothelial injuries. 

PMID- 25972664
TI  - A retained rectosigmoid foreign body: unusual presentation.
AB  - A variety of foreign bodies have been inserted in to the rectum for
      autoeroticism. However, their presence inside the bowel lumen for prolong period
      might not produce serious harm to the host, and discovery of such object during
      evaluation of rectal symptoms is not a surprise. Here we describe a 64-year-old
      male patient presented with rectal symptoms, and a rectosigmoid foreign body was
      discovered after 35 days of self-insertion. No serious life threatening events
      occurred during this period. This was easily removed by trans-anal approach under
      anesthesia. 

PMID- 25972665
TI  - A huge acquired smooth muscle hamartoma of the scrotum.
AB  - Smooth muscle hamartoma (SMH) is a rare benign proliferation of the smooth
      muscle. It usually arises on the back and proximal extremities, although it
      develops on the scrotum in rare cases. Here, we present a 58-year-old man who
      presented with a huge mass of the scrotum, which was first noticed 10 years
      previously. The scrotum was considerably enlarged and affected the patient's
      gait. We performed wide excision of the mass, measuring 32.5 * 20 * 14 cm in size
      and weighing 3600 g. The residual uninvolved scrotal skin flap was well
      vascularised and elastic, and the testis could be properly contained within the
      scrotum after primary closure of the defect. A split-thickness skin graft was
      used to resurface the skin defect of the penile shaft. The patient was satisfied
      with the shape and texture of the scrotum after reconstruction. The postoperative
      course was uneventful. We assess our experience in the successful reconstruction
      of a large penoscrotal skin defect using a scrotal skin flap and split-thickness
      skin graft. This procedure is safe and uncomplicated with the patient regaining a
      normal genital contour and satisfactory functional recovery. 

PMID- 25972666
TI  - Simultaneous Occurrence of a Rare Pancreatic Lymphoepithelial Cyst and Duodenal
      Mesenteric Castleman's Disease: a Case Report.
AB  - Pancreatic lymphoepithelial cyst is a rare pancreatic lesion of undetermined
      pathogenesis, which is a true pancreatic cyst. Castleman's disease is a rare
      lymphoproliferative disorder, and a mesenteric location is unusual. The
      simultaneous occurrence of the two diseases are rarer than metachronous ones and
      has not been reported to date. We present a case report of a patient with
      simultaneous occurrence of pancreatic lymphoepithelial cyst and duodenal
      mesenteric Castleman's disease. 

PMID- 25972667
TI  - Fecopneumothoax: a rare case of delayed colon diaphragmatic herniation following
      esophagectomy.
AB  - Diaphragmatic hernia after esophagectomy and, particularly, eventual
      fecopneumothorax is a rare complication. Furthermore, a delayed manifestation 10
      years after esophagectomy is an extremely rare situation. Herein, we report a
      surgical case of fecopneumothorax resulting from the perforation of
      intrathoracically herniated transverse colon 10 years after McKeown
      esophagectomy. 

PMID- 25972668
TI  - "Jodhpur bezoar": giant polyurethane bezoar.
AB  - Acute upper gastrointestinal obstruction due to foreign body ingestion is rare
      (<6 % of all small intestinal obstruction). Bezoars tend to grow slowly and only
      thereafter cause obstruction, if any. Rapid formation of a bezoar within hours of
      ingestion of the offending substance is a unique entity. Here, we present a case
      of a 22-year-old Indian male who was brought in the emergency department with
      history of ingesting chemicals used for refrigerator insulation, with suicidal
      intent. Within hours, he was operated for suspected perforation. And on the
      operation table, we came across surprisingly a cast extending from the whole of
      the esophagus to as far as 2 ft of proximal jejunum! Probably the first of its
      kind ever known! And no breach in the gut could be found in spite of free gas
      under the dome of diaphragm, probably due to the chemicals sealing the rent as it
      solidified! 

PMID- 25972669
TI  - Small bowel cavernous hemangioma complicated with intussusception: report of an
      extremely rare case and review of literature.
AB  - Cavernous hemangioma of the small intestine is a rare disease in adult patients.
      Intussusception caused by small bowel hemangioma is extremely rare. We report a
      20-year-old female presenting with lower abdominal pain and post-prandial
      bloating. Laboratory studies showed leukocytosis with left shifting and prominent
      anemia. Computed tomography of the abdomen revealed small bowel intussusception
      with bowel ischemia. Segmental resection of the intussuscepted jejunum was
      performed, and the diagnosis of cavernous hemangioma causing intussusception and
      anemia simultaneously was made. 

PMID- 25972671
TI  - Female urethral leiomyoma presenting with acute urinary retention-a rare case
      with unusual presentation.
AB  - Urethral leiomyoma is a rare benign tumor arising from smooth muscles of urethra.
      These tumors are more common in women than men, and few cases were reported in
      the literature. Presentation with acute urinary retention was rare. Proximal
      segment of urethra was commonly affected than the distal segment. We report here
      a case of urethral leiomyoma at the distal urethra presenting with acute urinary
      retention. 

PMID- 25972670
TI  - Management of infected pancreatic necrosis-the "step up" approach and minimal
      access retroperitoneal pancreatic necrosectomy.
AB  - Infected pancreatic necrosis (IPN) is associated with high morbidity and
      mortality. It is increasingly being recognized that noninvasive management,
      radiological guided drainage, and minimally invasive procedures rather than the
      traditionally advocated open necrosectomy are associated with a better outcome in
      IPN. We present a patient with IPN who was managed with the now popular "step up"
      approach and describe the procedure of Minimal access retroperitoneal pancreatic
      necrosectomy. 

PMID- 25972672
TI  - Parkes weber syndrome involving right lower limb: a case report.
AB  - Vascular malformations (VMs) are developmental abnormalities of the vascular
      system. Malformations may involve any segment of the vascular tree: arteries,
      capillaries, veins or lymphatics. High-flow arteriovenous malformations (AVMs)
      are associated with shunting of large amounts of arterial blood into the venous
      system; these lesions can have dynamic and dramatic hemodynamic manifestations,
      such as massive arteriolisation with gross venous engorgement, organomegaly of
      concerned anatomical region and high-output cardiac failure. Patients with Parkes
      Weber syndrome have clinically significant micro- or macrofistulous arteriovenous
      shunts, affecting usually one extremity. The patient has dilated, frequently
      visible pulsatile varicose veins and other visible signs of AV shunting. The
      abnormality is sporadic; it is likely a somatic mutation. There is frequent
      intraosseous involvement. The presence of high AV shunts differentiates Parkes
      Weber syndrome from Klippel-Trenaunay syndrome which is a clinical triad of
      capillary malformation, soft tissue and bone hypertrophy and venous and lymphatic
      malformations. The mutations in RASA 1 gene leads to Parkes Weber syndrome
      characterised by the presence of multiple, small (1-2 cm in diameter) capillary
      malformations mostly localized on the face and limbs. We report a case of
      congenital AVM of the lower limb causing cardiac decompensation. The patient was
      safely and successfully treated by performing a knee disarticulation. 

PMID- 25972673
TI  - Anteriorly placed splenic vein: a case report.
AB  - Splenic vein located anterior to pancreas is a rare congenital anomaly. To date,
      only one case has been reported in literature. A thorough knowledge of the normal
      anatomy, most frequent variations, and congenital and acquired anomalies of the
      spleno-portal axis is of great importance for hepatobiliary and pancreatic
      surgeons. It is therefore essential for preoperative evaluation of the anatomical
      details of the spleno-portal venous axis to be made by imaging. We report such a
      case of anteriorly placed splenic vein in a 40-year-old female prospective renal
      donor. To the best of our knowledge, this represents the second reported case of
      an anteriorly placed splenic vein. 

PMID- 25972674
TI  - Giant splenic lymphangiomatosis in adult: a diagnostic dilemma.
AB  - Cystic lymphangiomatosis of the spleen occurs secondary to developmental
      malformation of the lymphatic system. It is one of the rare entities generally
      seen in children. It is usually seen in children. We report a case of cystic
      lymphangiomatosis of the spleen occurring in an adult woman presenting with
      massive splenomegaly. Total splenectomy was considered to be the treatment of
      choice for making definitive diagnosis and to exclude the presence of malignancy
      or other causes of massive splenomegaly. 

PMID- 25972675
TI  - Traumatic pseudoaneurysm of bulbourethral artery managed by coil embolization.
AB  - Urethral injury is a common form of urogenital trauma in males. Urethral injuries
      can be diagnosed with ease in emergency due to the presence of blood clot at
      external urethral meatus or inability to catheterize the urethra. Stricture
      formation is usual sequelae of such injuries. Uncontrolled urethral hemorrhage is
      a relatively rare complication which can present either as immediate or delayed.
      Such injuries can be managed conservatively in majority; however, if uncontrolled
      may require interventional management. Such patients usually have underlying
      pseudoaneurysm formation or arteriovenous fistula. Here, we are reporting a case
      of bulbar urethral injury which presented with delayed uncontrolled urethral
      hemorrhage. On angiography, pseudoaneurysm arising from left bulbourethral artery
      with active urethral extravasation was noted and was managed with coil
      embolization. 

PMID- 25972676
TI  - A Sporadic Small Jejunal GIST Presenting with Acute Lower Gastrointestinal
      Hemorrhage: A Review of the Literature and Management Guidelines.
AB  - Gastrointestinal stromal tumors (GISTs) represent the majority of primary
      nonepithelial neoplasms of the digestive tract, most frequently expressing the
      KIT protein detected by immunohistochemical staining for the CD117 antigen.
      Jejunal GISTs account for approximately 10 % of GISTs. Patients usually present
      with abdominal discomfort. Jejunal GISTs may cause symptoms secondary to
      obstruction or hemorrhage. Pressure necrosis and ulceration of the overlying
      mucosa may cause gastrointestinal bleeding, and patients who experience
      significant blood loss may suffer from malaise and fatigue. Literature has
      classified small-bowel GISTs on the basis of size, and various established
      guidelines have advised conservative management of small jejunal GISTs (<2 cm).
      We here report the clinical, macroscopic, and immunohistological features of a
      small jejunal GIST presenting with acute lower gastrointestinal hemorrhage in a
      50-year-old postmenopausal woman necessitating an emergency laparotomy to control
      the bleed. The management of very small (<2 cm) small-bowel GISTs is
      controversial. While guidelines are primarily based on the risk of malignancy in
      GISTs, no guideline predicting the risk of complications in small-bowel GISTs
      exists. Hence, these tumors should be removed even if incidentally detected. 

PMID- 25972677
TI  - Laparoscopic transperitoneoscopic nephroureterectomy in a patient with situs
      inversus totalis.
AB  - This article discusses the case of a 78-year-old female with painless gross
      hematuria. Chest X-rays showed dextrocardia with situs inversus, and whole-body
      computed tomography scanning showed a renal mass in the right renal pelvis, no
      evidence of metastasis, and mirror-image organs with left-to-right transposition,
      which resulted in a diagnosis of situs inversus totalis (SIT). A laparoscopic
      transperitoneoscopic right nephroureterectomy was scheduled. To our knowledge,
      our case is the second case of laparoscopic nephroureterectomy in renal pelvic
      urothelial carcinoma with SIT to be presented, but it is the first case of
      laparoscopic transperitoneoscopic nephroureterectomy. Laparoscopic
      transperitoneoscopic nephroureterectomy was successfully performed in a renal
      pelvic urothelial carcinoma patient with SIT with a correct description of renal
      vascularity and abdominal anatomy. 

PMID- 25972678
TI  - Chronic gastritis in a gastric diverticulum misdiagnosed as a left adrenal mass.
AB  - Gastric diverticula are rare and usually asymptomatic. They are most frequently
      located on the posterior wall of the stomach. Many of them were reported as
      adrenal masses. Here, we present a 48-year-old male with a gastric fundus
      diverticulum that was misdiagnosed as a left adrenal mass on magnetic resonance
      imaging (MRI). Laparoscopic resection of the diverticulum was successfully
      performed, and histopathological examination revealed a true gastric diverticulum
      with moderate chronic gastritis. Although most cases of gastric diverticula are
      asymptomatic, to the best of our knowledge, this is the first reported case of
      chronic gastritis that developed in a gastric diverticulum. 

PMID- 25972679
TI  - Renal cell carcinoma presenting as Dysphagia.
AB  - Renal cell carcinoma presenting with dysphagia is rare. We report a case who
      presented with dysphagia as the only manifestations of renal malignancy. Biopsy
      from the pyriform fossa nodules revealed a clear cell neoplasm. Immuno
      histochemical analysis of tissue confirmed metastasis of renal cell carcinoma. 

PMID- 25972680
TI  - 'O' configuration of biliary-enteric drainage: a preventable surgical error.
AB  - Surgical errors in Roux limb reconstruction are not reported widely. A young male
      who underwent hepaticojejunostomy after biliary injury developed acute
      obstruction of the proximal jejunum. Barium study revealed the O configuration of
      alimentary limb-'O' sign. At laparotomy, he was found to have the alimentary limb
      joining on to itself and without any connection with the biliary limb. The O loop
      complex was resected, and Roux-en-Y construction was refashioned. He made an
      uneventful recovery and is well at one year follow-up. We have reviewed the
      literature and propose a classification system for such type of errors. Every
      effort should be made to prevent this complication. 

PMID- 25972681
TI  - Simultaneous radical gastrectomy and coronary artery bypass grafting: a case
      report.
AB  - Coexistence of coronary artery disease and cancer with both requiring surgical
      treatment at the same time is rare. A 74-year-old male underwent elective
      coronary artery bypass grafting for unstable angina. In preoperative workup, the
      patient was incidentally discovered to have anaemia secondary to occult blood
      loss in his stool. This led to a preoperative upper GI endoscopy which showed a
      gastric carcinoma. Since both conditions required surgery, it was decided to
      perform simultaneous coronary artery bypass grafting (CABG) followed by distal
      radical gastrectomy. CABG was done using low-dose heparin, and after closing
      sternotomy, the radical gastrectomy was performed. Postoperative recovery was
      uneventful, and patient was discharged in stable condition on day 14. Follow-up
      after 6 months revealed no recurrence. Feasibility of simultaneous CABG and
      gastric cancer surgery, in particular, and various management strategies, in
      general, is discussed. 

PMID- 25972683
TI  - Kikuchi's Disease: A Diagnostic Dilemma.
AB  - Cervical lymphadenopathy is one of the common presentations in present day
      surgical practise. The causes may vary from gastrointestinal malignancy
      indicating a grave prognosis to nonspecfic lymphadenopathy secondary to infection
      or trauma to the extremity which is self-limiting. Diagnosis most often requires
      contributions from pathologist as well as radiologist in addition to a detailed
      clinical examination. We are presenting a case of Kikuchi's disease which mimics
      tuberculosis and often leads to diagnostic dilemma. 

PMID- 25972682
TI  - Adult intestinal malrotation presenting as recurrent vomiting: a case report.
AB  - Gut malrotation is a congenital anomaly characterized by either lack of rotation
      or incomplete rotation of gut around axis of superior mesenteric artery. Most
      patients present within first year of life. Presentation during adult life is
      considered rare. Diagnosis of intestinal malrotation during adult life is most
      often by chance rather than by clinical acumen. Once diagnosed, treatment is
      based on the general principles of management of intestinal obstruction. We are
      presenting one such case in which CECT abdomen done to look for the diagnosis of
      acute pancreatitis leads us to the identification of intestinal malrotation. 

PMID- 25972684
TI  - Kasabach-Merritt Syndrome Associated With a Large Cavernous Splenic Hemangioma
      Treated With Splenectomy: A Surgeon's Introspection of an Uncommon, Little Read,
      and Yet Complex Problem-Review Article.
AB  - Cavernous hemangiomas of the spleen are small benign lesions found incidentally,
      majority of times while patients are being investigated for some other disease
      and patients remain asymptomatic otherwise for this condition. The natural
      history of cavernous hemangiomas of spleen is slow, symptoms or complications,
      when present, occur late, they are rarely large and can manifest as a palpable
      non-tender mass in the left upper quadrant. A very rare syndrome is associated
      with this condition called Kasabach-Merritt syndrome (KMS), which is defined as
      diffuse cavernous hemangioma of the spleen alongwith anemia, thrombocytopenia,
      and coagulopathy. Perioperative diagnosis can be confirmed by imaging study which
      can be CT, MRI, or ultrasound. Splenectomy is considered the treatment of choice
      for such patients with symptoms. To our knowledge, a very few cases have been
      reported so far. The purpose of writing this review article is the reporting of
      this rare case and to provide some experience related to the management of this
      condition in a patient with KMS. 

PMID- 25972685
TI  - Aggressive angiomyxoma of scrotum presenting as scrotal lymphedema in a case of
      postoperative carcinoma penis.
AB  - Aggressive angiomyxoma tumor is a rare tumor in males. We report a case of
      incidentally diagnosed aggressive angiomyxoma of scrotum presenting as scrotal
      lymphedema in a patient who underwent partial penectomy and radiotherapy for
      carcinoma penis. 

PMID- 25972686
TI  - Gravid uterus in neglected incisional hernia with skin defect-a clinical
      challenge.
AB  - Incisional hernia during pregnancy with whole of gravid uterus as the content of
      the hernia sac is a rare occurrence. When such hernia is associated with skin
      defect over the sac, the management gets complicated. Very few such cases are
      reported in the literature. There is no consensus on the management of these
      cases in the available literature. Here, we are reporting two such cases managed
      in different ways and reviewed the literature. LEVEL OF EVIDENCE: Level V,
      Clinical cases.

PMID- 25972687
TI  - Traumatic abdominal wall hernia associated with small bowel injury-case report.
AB  - Traumatic abdominal wall hernias (TAWHs) are rare. Their diagnosis is mostly
      clinical and can be overlooked in the setting of trauma and distracting injuries
      or they can be misinterpreted as parietal hematomas. Associated lesions can
      influence decision making regarding time of operation and surgical technique. Our
      case highlights the management of a high-energy TAWH that associates a small
      bowel traumatic lesion. Surgical repair of TAWHs should follow general hernia
      repair principles. Further exploration of surgical options is necessary for a
      consensus to be reached. 

PMID- 25972688
TI  - Intussusception caused by an enterolith from a jejunal diverticulum.
AB  - We are reporting a case of intestinal obstruction in a lady patient and
      peroperatively, it turned out to be a case of intestinal obstruction due to
      intussusception caused by an enterolith originating from one of multiple jejunal
      diverticula. It was a rare cause of intestinal obstruction, and the presentation
      was very rare in the literature. The diagnosis and management are thus delayed. 

PMID- 25972689
TI  - Tuberculosis of the Thyroid-a Diagnostic Enigma.
AB  - Thyroid tuberculosis is very uncommon even in countries where tuberculosis is
      endemic. It is commonly seen secondary to tubercular infection of other organ or
      tissue by hematogenous spread. There are many different presentations of thyroid
      tuberculosis. Before the advent of fine needle aspiration cytology (FNAC), all
      patients had surgery and thyroid tuberculosis was diagnosed only on biopsy of
      specimen. Nowadays, FNAC can confirm the diagnosis in many cases, and the patient
      can be cured by standard anti-tubercular treatment without the need for surgery.
      Surgery is required only when there is suspicion of malignancy and FNAC is
      inconclusive. 

PMID- 25972690
TI  - A Case of Recurrent Eccrine Porocarcinoma with Regional Lymph Nodal Metastasis,
      Arising on a Bowen's Disease Patch.
AB  - Eccrine carcinomas are very rare, comprising only less than 0.005 % of all
      cutaneous carcinomas, as reported by Goellner et al. (Cancer 56:1147-1162, 1985).
      We are reporting a case of recurrent eccrine porocarcinoma (EPC) with regional
      lymph nodal metastasis, which arose on a Bowen's disease patch. Wide local
      excision of the lesion with lymph node dissection and excision of the Bowen's
      disease was done. 

PMID- 25972691
TI  - Synchronous collision neuroendocrine tumor and rectal adenocarcinoma: a case
      report.
AB  - Collision tumors are thought to arise from the accidental meeting of two
      independent tumors. Adenocarcinoma is the most common malignant rectal tumor,
      while neuroendocrine tumor (NET) is relatively rare. Due to the endoscopy and
      reporting, the overall incidence of NETs was increasing recently but still less
      than 1 per 100,000. This means that a combination of an adenocarcinoma and NET is
      a very rare finding and an actual collision of these tumors even more so. We
      report here a highly unusual case of a 64-year-old woman who had collision tumors
      composed of a primary rectal adenocarcinoma and NET showing a "side by side"
      pattern. Resection margins are free of both the tumors. The postoperative course
      was uneventful. The patient underwent a protocol CT scan at 3 months after
      surgery, which did not show any recurrence. Both the malignant adenocarcinoma and
      the NET would make a great influence in the rest lifetime and a follow up will be
      continued, although the CT did not show any recurrence until now. To the best of
      our knowledge, this is the first reported case of such an occurrence. 

PMID- 25972692
TI  - Rare case of gastrointestinal stromal tumor presenting with scrotal metastasis.
AB  - While gastrointestinal stromal tumors frequently metastasize, the scrotum is an
      extremely rare site of involvement. This case is of a 48-year-old male who,
      having undergone debulking surgery for metastatic gastrointestinal stromal tumor
      (GIST) of the small intestine 2 years ago, presented with bilateral scrotal
      swelling. Ultrasound showed hypoechoic mass lesions surrounding the testis and
      epididymis bilaterally with extension into the spermatic cord and biopsy
      established a diagnosis of metastatic GIST of the scrotum. As the processus
      vaginalis is an extension of the peritoneal cavity, we postulate that it may
      serve a route of spread in malignancies that involve the peritoneal cavity, as in
      this case. 

PMID- 25972693
TI  - Amoeboma-lest we forget!!!
AB  - Amoebiasis is an infection with the parasitic intestinal protozoan Entamoeba
      histolytica (E. histolytica). Most infections are usually asymptomatic, but the
      disease spectrum can range from dysentery to extraintestinal infections,
      including liver abscesses. The management of a 68-year-old male with amoeboma, a
      rare manifestation of intestinal amoebiasis, is described along with a review of
      literature. 

PMID- 25972694
TI  - Traumatic abdominal wall hernia: a case report.
AB  - Traumatic abdominal wall hernias are rare injuries despite the high incidence of
      blunt abdominal traumas. The mechanism of this injury includes a sudden increase
      in intra-abdominal pressure and extensive shear forces applied to the abdominal
      wall. We report a case of traumatic hernia of the anterior abdominal wall in a 42
      year-old woman presented with blunt injury of the upper abdomen. She was attacked
      by a bull. She had a clinically evident abdominal fascial disruption with intact
      skin and was hemodynamically stable. The presence of localized pain, bruising and
      a reducible swelling or a cough impulse suggested the diagnosis. An emergency
      mesh repair of the defect was performed, and she recovered well. 

PMID- 25972695
TI  - Intramedullary fixation of pertrochanteric fractures after hip resurfacing
      arthroplasty - Do we have the answer? Case report and literature review.
AB  - OBJECTIVE: To report a case of a peri-prosthetic hip fracture fixed using a
      previously unreported technique of intramedullary nailing with dual proximal
      fixation. CASE SUMMARY: An 81-year-old nursing home resident suffered a multi
      fragmentary peri-prosthetic hip fracture around a Birmingham Hip Resurfacing
      arthroplasty (BHR), which was fixed using a novel technique. DISCUSSION: Such
      fractures pose a significant surgical dilemma with regards to the optimal method
      of treatment. The increasing popularity of these implants suggests that these
      fractures will become increasingly common. CONCLUSION: We believe that our
      technique provides a practical and satisfactory solution to these fractures.

PMID- 25972696
TI  - Abnormal karyotypes in osteochondroma: Case series and literature review.
AB  - BACKGROUND: Osteochondroma is the most common benign bone tumor. However, there
      are infrequent studies karyotyping solitary osteochondromas. METHODS:
      Retrospective review of the University of California, Los Angeles pathology
      database was performed for karyotype analyses (N = 522 specimens). RESULTS: Two
      previously undescribed karyotypes were identified. First, was a karyotype showing
      paracentric inversion of chromosome 7. Second, was a karyotype showing monosomy
      3, 6 and 13. CONCLUSIONS: Abnormal karyotypes may be more frequently encountered
      in osteochondroma than previously understood. However, the clinical significance
      of these abnormalities are yet unknown.

PMID- 25972697
TI  - Predictors of early failure in young patients with displaced femoral neck
      fractures.
AB  - INTRODUCTION: This study compares early failure rates of sliding hip screw (SHS)
      and cannulated screw (CS) constructs in young patients. METHODS: Patients <60
      years of age, with displaced femoral neck fractures treated with CS or SHS
      fixation were included. Primary outcome was failure within 6 months. RESULTS: One
      patient (3%) with SHS fixation and 6 patients (21%) with CS fixation failed
      within 6 months (P = 0.04). Regression analysis demonstrated type of fixation (P
      = 0.005) and reduction quality (P = 0.04) are independent predictors of early
      failure. CONCLUSIONS: SHS constructs demonstrate a significantly lower short-term
      failure rate than CS constructs.

PMID- 25972698
TI  - Late recurrence of developmental dysplasia of the hip following Pavlik harness
      treatment until normal ultrasound appearance.
AB  - PURPOSE: Establish whether recurrent dysplasia once a dysplastic hip has been
      treated to ultrasonographic normality is possible. METHODS: 370 babies were
      referred to a hip ultrasound clinic from June 2005 to 2007 to assess for
      dysplasia. 96 dysplastic hips underwent appropriate treatment until normal hip
      morphology achieved on follow-up ultrasounds. Minimum further 12 months follow
      up. RESULTS: 3 children (4%) developed late recurrence of dysplasia. Two required
      a plaster hip spica. One had an additional adductor tenotomy. One required late
      pelvic osteotomy. CONCLUSION: This study highlights the need for long-term follow
      up of dysplastic hips with an early pelvic X-ray at around six months.

PMID- 25972699
TI  - Thromboembolic disease after knee arthroplasty is rare in Southern Iran.
AB  - BACKGROUND: Thromboembolic disease (TED) after knee arthroplasty occurs
      infrequently in Iran. The aim of this study was to examine the incidence of TED
      in patients with osteoarthritis undergoing knee replacement in Southern Iran
      while on prophylaxis. MATERIALS & METHODS: In a case series study from January to
      December 2012, 100 consecutive total knee arthroplasty (TKA) candidates were
      evaluated for TED by clinical evaluation and Doppler sonography preoperatively
      and 2 months postoperatively and by clinical evaluation one year after surgery.
      The patients in this study randomly received either warfarin or enoxaparin
      prophylactically. RESULTS: A total of 77 women and 23 men with mean age of 67
      years (52-82 years) entered the study. The average hemoglobin drop of 2.7 g with
      warfarin and 3.3 with enoxaparin was observed. No case of TED, pulmonary embolus
      (PE), major bleeding, post-thrombotic syndrome, or hemarthrosis was observed.
      CONCLUSION: No clinically significant DVT was found using either enoxaparin or
      warfarin prophylaxis after TKA in Southern Iran. Relatively excessive
      postoperative bleeding was observed, particularly with enoxaparin.

PMID- 25972700
TI  - Comparison of cannulated screws with FiberWire or stainless steel wire for
      patella fracture fixation: A pilot study.
AB  - PURPOSE: This pilot study tested whether FiberWire provides similar protection to
      steel wire against repair displacement in patella fractures. METHODS: Thirteen
      cadaver knees were cyclically loaded with 10 cycles (0-90 degrees  flexion) and
      fracture displacement was recorded. Fixation methods were also tested in load to
      failure (>3 mm displacement). RESULTS: There was no difference between wire types
      in fracture displacement (1.4 mm +/- 0.33 mm vs 1.2 mm +/- 0.34 mm, respectively;
      p = 0.418) or in the load to failure (714.7 N +/- 110.9 N vs 744.5 N +/- 92.8 N,
      respectively; p = 0.360). CONCLUSION: FiberWire provides similar protection to
      steel wire against repair displacement after fixation of patellar fractures.

PMID- 25972701
TI  - Reverse shoulder arthroplasty: The Singapore General Hospital experience and a
      simple method of measuring change in the center-of-rotation.
AB  - INTRODUCTION: This study reviews the outcomes of reverse shoulder arthroplasty
      (RSA) and introduces a novel method of measuring changes in the center-of
      rotation (COR) of the shoulder joint post-operatively. METHODS: We performed 10
      reverse shoulders in 2011. Patients were evaluated pre-operatively and post
      operatively using the Constant Score. The COR of the shoulder was determined pre-
      and post-operatively on radiographs and the differences were analysed. RESULTS:
      There was significant improvement in Constant Scores post-operatively with
      reduction in pain and increase in strength. Medialisation but not distalisation
      of the COR was achieved. DISCUSSION: Longer follow-up studies and studies on
      survivalship are required.

PMID- 25972702
TI  - Stress shielding in the bony chain of leg in presence of varus or valgus knee.
AB  - AIMS: The aim was to assess how the stress shielding can influence the integrity
      and resistance of bones in presence of a misalignment. METHODS: Three finite
      elements models have been developed: a normal one, and two varus and valgus knee
      ones. RESULTS: The obtained results reveal interesting consequences deriving by a
      wrong disposition of parts which compose the skeletal chain of the leg.
      CONCLUSION: The most dangerous conditions occur in the contact interface between
      pelvis and hip of the femur, for the valgus knee configuration, and for the varus
      one, at the contact interface around the knee zone.

PMID- 25972704
TI  - Shortening femoral osteotomy with stemmed resurfacing total knee arthroplasty for
      severe flexion contracture in Juvenile Rheumatoid Arthritis.
AB  - Juvenile Rheumatoid Arthritis (JRA) is a progressive disease characterized by
      pain, swelling, and loss of motion in the joints of adolescents. Total knee
      arthroplasty (TKA) can be indicated, during the adolescent years, in patients
      with advanced JRA to alleviate pain and improve function. Because of the relative
      infrequency of TKA in patients with JRA, evaluation of the type of TKA performed
      and the results merit review. This case report present two distinct operations
      performed to obtain full extension. 1. Distal femoral resection with conversion
      to hinged arthroplasty. 2. Femoral shortening osteotomy with resurfacing TKA. 

PMID- 25972703
TI  - Does K-wire position in tension band wiring of olecranon fractures affect its
      complications and removal of metal rate?
AB  - BACKGROUND: Despite the recognised complications of migration of wires and soft
      tissue irritation, tension band wiring (TBW) remains the gold standard for
      fixation of displaced, minimally comminuted olecranon fractures. There is much
      variation in placement of the K-wires with current AO guidance stating that each
      wire should be drilled through the anterior cortex and then backed up by 1 cm.
      The aim of this study was to examine the effect of K-wire position
      (intramedullary vs. transcortical) on stability of the construct and significant
      local complications. METHODS: All patients who underwent TBW for an isolated
      olecranon fracture in our trauma unit between 1/1/2009 and 31/12/2011 were
      included in this retrospective study. Mean follow-up was 14 months (range 5-29
      months). Data was gathered from medical records and radiographs. The outcome
      measured was removal of metal due to complications such as wound problems or
      proximal migration of wires as standard practice within out trauma unit. RESULTS:
      Sixty-three patients met the inclusion criteria. Forty-seven had an
      intramedullary compared with 16 with transcortical configuration (ratio 3:1).
      Nine patients (19%) with intramedullary K-wires required removal of metalwork -
      seven due to prominent metalwork and two with wound infection. Four patients
      (25%) with transcortical K-wires required removal of metalwork - three due to
      prominent metalwork and one with failure of metalwork. There was no significant
      statistical difference between transcortical and intramedullary K-wire placement
      with regards to complication rates following tension band wiring of an isolated
      olecranon fracture requiring removal of metal (Chi squared test with Yates'
      correction p = 0.89). CONCLUSION: We concluded that we found no difference in
      complications or metalwork removal rate in the placement of K-wire in tension
      band wiring for isolated olecranon fracture. We recognise our study was limited
      by small numbers and is based on the experience of one trauma unit.

PMID- 25972705
TI  - Anterior scoliosis surgery the state of art procedure.

PMID- 25972706
TI  - Vertical facetal instability: Is it the point of genesis of spinal spondylotic
      disease?

PMID- 25972707
TI  - Can foramen magnum decompression surgery become historical?

PMID- 25972708
TI  - Posterior atlantoaxial 'facetal' instability associated with cervical spondylotic
      disease.
AB  - AIM: The association of single or multiple level cervical spondylotic disease
      with atlantoaxial instability is assessed. The implications of identifying and
      treating atlantoaxial instability in such an association are highlighted.
      MATERIALS AND METHODS: The analysis is based on an experience with 11 patients
      treated during the period June 2013-June 2014. All patients had single or
      multilevel cervical spondylotic disease. The spinal canal compromise and evidence
      of cord compression was evident on imaging in the cervical subaxial spine and was
      related to disc bulges and osteophytic bars. There was no or relatively
      insignificant compression of the cervicomedullary cord by the odontoid process.
      There was no evidence of odontoid process-related instability on dynamic imaging.
      Apart from presence of features of cervical spondylosis, investigations and
      surgical exploration and direct manual handling of the facets revealed evidence
      of Type B (posterior) atlantoaxial 'facetal' instability in all patients. Our 5
      point clinical grading system and Japanese Orthopaedic Association (JOA) scores
      were used to monitor the patients both before and after surgery and at follow-up.
      Surgery involved both at lantoaxial and subaxial cervical fixation. During the
      average period of follow-up of 9 months (5-17 months), all patients showed
      remarkable and gratifying neurological recovery. CONCLUSION: We conclude that
      atlantoaxial facetal instability can be 'frequently' associated with cervical
      spondylosis and needs surgical stabilization. Our surgical outcome analysis
      suggests that missing or ignoring the presence of atlantoaxial facetal
      instability can be an important cause of suboptimal result or failure of surgery
      for cervical spondylotic myelopathy.

PMID- 25972709
TI  - Stabilization of metastatic lesions affecting the second cervical vertebra.
AB  - PURPOSE: Metastatic spine disease is an ever-increasing burden on health care
      systems. Certain levels in the spine confer unique biomechanical characteristics
      and hence are of interest. Isolated C2 lesions are rare. We aimed to review our
      results in surgical management of C2 lesions. MATERIALS AND METHODS: We reviewed
      all surgical stabilizations of metastatic spine lesions over the preceding 4
      years. Six patients with C2 lesions were identified. Of these five underwent
      surgical stabilization primarily for disease affecting the second cervical
      vertebra. Case notes and radiology were reviewed to determine presentation,
      outcomes and complications. RESULTS: Cases were treated primarily by posterior
      instrumentation from either occiput or C1 to the subaxial cervical spine. The
      median survivorship after surgery was 283 days. There were no cases of infection,
      VTE or implant failure. There were no cases of neurologic deterioration with all
      maintaining Frankel E grading. CONCLUSION: Metastatic lesions affecting the
      second cervical vertebra are rare. A variety of stabilization options tailored to
      the individual lesions, including occipitocervical fixation, in this small series
      was successful in maintaining stability and resolution of symptoms.

PMID- 25972710
TI  - The impact of steroids, methotrexate, and biologics on clinical and radiographic
      outcomes in patients with rheumatoid arthritis undergoing fusions at the
      craniovertebral junction.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory disease that affects the
      craniovertebral junction (CVJ). Patients may suffer from atlantoaxial instability
      (AAI) and basilar invagination (BI) with variable presentations ranging from pain
      to quadriparesis. Managing these patients is often challenging due to their
      chronic use of steroids, methotrexate, and biologics; which impedes bone and
      wound healing. We report our experience with the surgical management of these
      patients undergoing fusions at the CVJ. MATERIALS AND METHODS: We conducted a
      retrospective study identifying all patients with the diagnosis of RA who
      underwent spinal fusions at our institution over the past 11 years. A total of
      205 patients were identified amongst which 18 patients (8.8%) who underwent 20
      fusions involving the CVJ. Demographic, clinical, and radiographic data were
      analyzed. RESULTS: Five patients had AAI and 13 patients had BI. Two patients
      with C1-2 fusions underwent reoperation: One for pseudoarthrosis and one for BI.
      The average preoperative Nurick was 1.4 and improved to 0.5 postoperatively (P <
      0.001). After conducting analyses stratified by dichotomous preoperative
      variables, the presence of steroids, methotrexate, biologics, and prednisone
      dosage less than 7.5 mg did not affect outcomes. Prednisone dosages >=7.5 mg had
      significantly smaller improvements in Nurick score compared to patients not on
      steroids or on prednisone dosages <7.5 mg (0.40 vs 1.36, P = 0.042). Similarly,
      patients on biologics had significantly smaller improvements in Nurick score
      compared to patients not on biologics (0.27 vs 1.16, P = 0.038). CONCLUSION:
      Fusions at the CVJ in patients with RA on daily prednisone dosages of less than
      7.5 mg and/or methotrexate can be performed safely with good outcomes, fusion
      rates, and acceptable complication profiles. Daily prednisone dosages of more
      than 7.5 mg or biologics may impact clinical outcomes.

PMID- 25972711
TI  - Simple facet joint repair with dynamic pedicular system: Technical note and case
      series.
AB  - PURPOSE: Facet joints are important anatomical structures for the stability of
      spine. Surgical or degenerative damage to a facet joint may lead to spinal
      instability and causes clinical problems. This article explains the importance of
      facet joints, reviews facet replacement systems, and describes a simple and
      effective method for facet replacement after surgical removal of facet joints.
      MATERIALS AND METHODS: Ten patients were operated with the diagnosis of
      unilateral nerve root compression secondary to facet degeneration. The
      hypertrophic facet joints were removed with microsurgical techniques and the
      roots were decompressed. Then, a unilateral artificial facet joint was created
      using two hinged screws and a dynamic rod. RESULTS: The clinical outcome of all
      the patients was determined good or excellent at second and last follow-up (mean
      13.3 months) controls using visual analog scale (VAS) and Oswestry Disability
      Index (ODI) scores. Radiological evaluations also demonstrated no implant-related
      complications. CONCLUSIONS: The authors suggest that, if removal of a facet joint
      is necessary to decompress the nerve roots, the joint can be replaced by a
      construct composed of two hinged screws connected by a dynamic rod. This simple
      system mimics the function of a normal facet joint and is an effective technique
      for unilateral facet joint replacement.

PMID- 25972713
TI  - Trigeminal neuralgia secondary to basilar impression: A case report.
AB  - We report a rare case of trigeminal neuralgia. A 23-year-old woman with a history
      of 1 year of typical trigeminal neuralgia manifested the characteristics of
      basilar impression. Magnetic resonance imaging (MRI) demonstrated basilar
      impression, deformity of the posterior fossa with asymmetry of petrous bone, and
      compression of medulla oblongata in the topography of the odontoid apophysis. The
      operation was performed through a suboccipital craniectomy. The neuralgia
      disappeared after surgery and remains completely resolved until today. This is
      the second reported case of trigeminal neuralgia in a patient with basilar
      impression in Brazil. 

PMID- 25972712
TI  - The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery
      vasospasm on descending colon dilatation following spinal subarachnoid
      hemorrhage: An experimental study; first report.
AB  - CONTEXT: Somato-sensitive innervation of bowels are maintained by lower segments
      of spinal cord and the blood supply of the lower spinal cord is heavily dependent
      on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid
      hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been
      elucidated as a cause of bowel dilatation so far. AIMS: The goal of this study
      was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar
      subarachnoid hemorrhage (SAH) on bowel dilatation severity. SETTINGS AND DESIGN:
      An experimental rabbit study. MATERIALS AND METHODS: The study was conducted on
      25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13),
      serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH
      was performed. After 21 days, volume values of descending parts of large bowels
      and degenerated neuron density of L5DRG were analyzed. STATISTICAL ANALYSIS USED:
      Statistical analysis was performed using the PASW Statistics 18.0 for Windows
      (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were
      used. The statistical significance was set at P < 0.05. RESULTS: The mean volume
      of imaginary descending colons was estimated as 93 +/- 12 cm(3) in the control
      group and 121 +/- 26 cm(3) in the SS group and 176 +/- 49 cm(3) in SAH group.
      Volume augmentations of the descending colons and degenerated neuron density
      L5DRG were significantly different between the SAH and other two groups (P <
      0.05). CONCLUSION: An inverse relationship between the living neuronal density of
      the L5DRG and the volume of imaginary descending colon values was occurred. Our
      findings will aid in the planning of future experimental studies and determining
      the clinical relevance on such studies.

PMID- 25972714
TI  - Dystrophic thoracic spine dislocation associated with type-1 neurofibromatosis:
      Case report and rationale for treatment.
AB  - The authors report a rare case of spontaneous dystrophic thoracic spine
      dislocation in a 14-year-old boy with neurofibromatosis type 1 (NF-1).
      Anteroposterior and lateral standing radiographs showed a dysplastic
      kyphoscoliotic deformity, with the thoracic kyphosis and scoliosis measuring 75
      degrees  and 69 degrees , respectively. Three-dimensional reconstruction after
      computed tomography demonstrated spondyloptosis at T5-T6 with overlapping of T5
      over T6 and T7. The patient underwent circumferential fusion with anterior
      fibular strut grafting mechanically secured between the inferior and superior
      endplates of T5 and T7 followed by an instrumented posterior fusion from T2 to L1
      and thoracoplasty. There was satisfactory resolution of the deformity with
      stabilization at the last follow-up evaluation. 

PMID- 25972715
TI  - Acute hemorrhage within intradural extramedullary schwannoma in cervical spine
      presenting with quadriparesis.
AB  - Schwannoma with acute hemorrhage is rarely seen. A 44-years-old male patient
      presented with complaint of neck pain and acute onset of quadriparesis. Magnetic
      resonance imaging (MRI) of his cervical spine revealed evidence of an intradural
      extramedullary tumor with intratumoral acute hemorrhage. He was operated in
      emergency and the mass was found to be schwannoma with acute hemorrhage. Post
      operatively the patient improved significantly. Though schwannomas show
      microscopic intratumoral hemorrhage and necrosis at times, schwannoma with acute
      hemorrhage resulting acute onset of neurological deficit is very uncommon. 

PMID- 25972716
TI  - Complete avulsion of spinal cord and cauda equina: A case report.
AB  - Pure ligamentous flexion-distraction injuries of the lumbar spine are relatively
      rare and even less commonly associated with neurologic compromise. They are
      largely related to the use of lap belt restrains during motor vehicle accidents.
      We report a 19-year-old female backseat passenger wearing a lap belt who was
      involved in a head-on collision. On admission she was paraplegic, with a T12
      sensory level and no motor and sensory function of S4-S5 (American Spinal Injury
      Association (ASIA) A). Plain X-ray and computerized axial tomography (CAT) spine
      showed a flexion-distraction injury at the L3-L4 level. During surgery in the
      interspinous space a conus medullaris was identified, which was completely
      severed from the spinal cord. The patient underwent a fusion procedure and made a
      good recovery. Twelve months after surgery she was able to walk with a knee-ankle
      foot orthosis, she has no motor function below knees, no sensation below L2, and
      no voluntary bladder control. Although described type of injury is very rare, one
      should always have in mind devastating consequences of inadequate or improperly
      worn seatbelts. 

PMID- 25972717
TI  - Intractable vomiting caused by vertebral artery compressing the medulla: A case
      report.
AB  - Vertebral artery compressing the medulla and causing intractable vomiting has
      only been reported once previously. We report a case of a 69-year-old woman with
      intractable nausea and vomiting causing a 50 pound weight loss and who failed
      medical management and whose symptoms were completely reversed following
      microvascular decompression (MVD). 

PMID- 25972718
TI  - Cervical myelopathy due to single level disc herniation presenting as
      intramedullary mass lesion: What to do first?
AB  - Cervical myelopathy (CM) is mostly a degenerative process ending in myelopathic
      and/or radiculopathic syndromes. On T2-weighted magnetic resonance imaging (MRI),
      CM appears as a hyperintense area near the spondylotic spine. This high intensity
      signal depends on the impact of outer forces and their duration. It also
      determines the prognosis of the surgical candidate. A 40-year-old male patient
      admitted to our clinic with right upper extremity weakness and hypoesthesia that
      had started 2 months earlier. On neurological examination there was 2/5 motor
      weakness of right biceps brachii, and hypoesthesia over right C6 dermatome. Right
      upper extremity deep tendon reflexes were hypoactive, but lower ones were
      hyperactive. After clinical and radiological work-up, preliminary diagnosis was
      directed to a spinal intramedullary tumor. Total resection of the herniated
      cervical disc fragment and the mass lesion was managed. Pathology of the mass
      lesion was compatible with subacute infarct tissue and inflammatory response.
      Final diagnosis was CM under effect of cervical disc herniation. Contrast
      enhanced spinal cord myelopathic lesions are very rare and resemble much more
      tumors and inflammatory processes. However, the principal treatment approach
      totally differs depending on pathology. When there are both a disc herniation and
      a high clinical suspicion; biopsy should be delayed. The most probable solution
      will be surgery for the disc disease with thorough preoperative scanning of
      vascular malformations; clinical and radiological close follow-up after surgery.
      Biopsy or surgical resection can be performed if patient deteriorates despite the
      primary surgery. 

PMID- 25972719
TI  - Intervertebral disc calcification in childhood: Case report and review of
      relevant literature.

PMID- 25972720
TI  - Dhatrilauha: Right choice for iron deficiency anemia in pregnancy.
AB  - BACKGROUND: Anemia in pregnancy is multi-factorial. Iron deficiency anemia (IDA)
      is the most common one. Major cause is increased demand of iron during pregnancy.
      In Ayurveda, under Pandu-Roga the features of anemia are described. It is
      characterized by Vaivarnyata or Varnanasha (change/destruction in normal color of
      the body), a disorder of Pitta vitiation. Ayurvedic management is an effective
      way of curing anemia in general by a large number of Lauha preparations of which
      Dhatrilauha has been used widely for centuries. AIM: To evaluate the effect of
      Dhatrilauha in the management of IDA based on the scientific parameters among
      pregnant patients. MATERIALS AND METHODS: A total of 58 cases were selected by
      simple randomized sampling method as per inclusion criteria of pregnant women
      between 4(th) and 7(th) months of pregnancy with a clinical diagnosis and
      laboratory confirmation of IDA. Dhatrilauha 500 mg in two divided doses after
      food with normal potable water were given for 45 days with three follow-ups, each
      of 15 days intervals. Final assessment was done after completion of 45 days and
      results were statistically analyzed by using Cochran's Q-test and Student's t
      test. RESULTS: Dhatrilauha showed statistically significant (P < 0.01)
      improvement in the majority of sign-symptoms and objective parameters such as
      weakness, fatigue, palpitation, effort intolerance, breathlessness, heartburn,
      pallor, constipation, hemoglobin, red blood cells (RBC), hematocrit, mean
      corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution
      width, mean platelet volume, serum iron, and total iron binding capacity.
      CONCLUSION: Dhatrilauha possesses many fold effectiveness in anemia (IDA), which
      was evidenced with the significant results obtained in the majority of parameters
      in this study.

PMID- 25972721
TI  - Multiple aneurism (Siraja Granthi) observed during cadaveric dissection.
AB  - Acharya Sushruta has emphasized the method and importance of dissection to study
      anatomy practically. Perfect knowledge of anatomy is vital for practicing
      surgeons and hence training of dissecting the dead body was considered as
      mandatory for surgeons. Though dissection techniques may give the perception of
      the structure of organs, the pervading and subtle consciousness in the body can
      be experienced with the eyes of knowledge and penance only. Though standard
      anatomy is defined based on statistical inferences on comparing large number of
      subjects, individual variations and exceptional structural specialties tend to
      occur quite frequently. Proper recording and publication of such instances would
      strengthen the knowledge base of the science. During the routine cadaveric
      dissection in the anatomy lab, multiple aneurisms (Siraja Granthi) in the
      abdominal aorta and femoral artery of 55-year-old male cadaver were observed.
      Such pathological variations are uncommon but clinically significant. Rupture of
      aneurysms or clot formation inside the lumen can produce serious complications in
      living condition. Enhancing size of the aneurysm producing pressure effect on the
      nearby structures can be the other reason for the surgical intervention. A good
      number of these can remain asymptomatic for a considerable period. As the
      clinical consequences are wide varying, the disease is of interest to physicians,
      as well as surgeons. 

PMID- 25972722
TI  - Preliminary pharmacognostic and phytochemical standardization of Dhataki
      [Woodfordia fruticosa (L.) Kurz.] leaves.
AB  - BACKGROUND: Woodfordia fruticosa (L.) Kurz., known as Dhataki, is an important
      medicinal plant used in Ayurveda. Recent studies on leaf showed that it contains
      important chemical constituents responsible for biological activities. The ethnic
      folk from India and Nepal are using the leaf to treat ulcers, rheumatism, fever,
      hemoptysis and as a disinfectant. It is also reported to be used in perfume,
      leather and textile industries. AIM: To investigate preliminary pharmacognostical
      and phytochemical parameters of leaf to standardize the drug. MATERIALS AND
      METHODS: Identification of plant was done as per the standard guidelines given in
      the floras. Macro and microscopic evaluation performed as per the routine
      laboratory procedures. Phytochemical, physico-chemical, florescence analysis,
      behavior of powdered drug have been conducted as per the WHO guidelines. RESULTS:
      Unique arrangement of the vascular bundle in mid rib region is observed. Aqueous
      and alcoholic extracts showed the presence of alkaloids, phenols, tannins, and
      flavonoids. CONCLUSION: The findings of this study will be helpful in the
      identification of Dhataki leaf.

PMID- 25972723
TI  - Antibacterial activity of Withania somnifera against Gram-positive isolates from
      pus samples.
AB  - BACKGROUND: Withania somnifera is an important medicinal plant that has been used
      in Ayurvedic and indigenous medicine since ancient times. In the view of its
      varied therapeutic potential, it has also been the subject of considerable modern
      scientific attention. Attention has been drawn to antibacterial activity of the
      plant and its metabolites due to the challenge on growing antibacterial resistant
      pathogens. AIM: To examine the antimicrobial potential of leaf extract of W.
      somnifera against Gram-positive cocci. MATERIALS AND METHODS: In this study, leaf
      extract of W. somnifera was used to examine their antimicrobial potential against
      Gram-positive cocci (n = 20) from pus samples of patients admitted in Government
      Medical College, Haldwani. Agar well diffusion method was used by taking
      methanolic leaf extract of W. somnifera. RESULTS: It was observed that the
      methanolic leaf extract of W. somnifera was very effective in inhibiting the test
      pathogens including methicillin resistant Staphylococcus aureus and Enterococcus
      spp., with an average zone of inhibition of 20.6 mm and 19.4 mm at 2 mg/ml (100
      MUl) concentration, respectively. CONCLUSION: These results indicate that the
      antimicrobial property of W. somnifera leaf supports the traditional use of the
      plant in therapeutic use against microbial infections.

PMID- 25972724
TI  - Effect of Triphala on dextran sulphate sodium-induced colitis in rats.
AB  - BACKGROUND: Herbal products from Ayurveda were always in the forefront in
      providing leads to new drug discovery. Triphala, an ancient Ayurvedic herbal
      formulation comprises of equal portions of Amalaki, Bibhitaki and Haritaki and is
      used extensively for constipation, as an anti-inflammatory, analgesic, anti
      arthritic, hypoglycemic and an anti-aging agent. AIM: To evaluate the effect of
      Triphala on dextran sulphate sodium induced colitis in rats. MATERIALS AND
      METHODS: Present study carried out in total five groups (n = 6 in each group);
      first group served as normal, second group control, third group standard control
      and remaining two as test drug groups. Mesalzine was used as a standard drug for
      comparison. Two doses (150 mg/kg and 300 mg/kg) of Triphala were given as
      treatment for two separate groups of colitis rats for 7 days. C-reactive protein,
      superoxide dismutase, catalase, malondialdehyde levels were evaluated and
      histological study of the distal colon was conducted. RESULTS: The colitis rats
      treated with higher dose of Triphala (300 mg/kg) exhibited normal parameters
      similar to normal control group animals, which is on par with standard drug
      mesalzine effect. CONCLUSION: The results suggest that Triphala (300 mg/kg) has a
      considerable and reliable effect in reducing colitis in rats. This effect can be
      attributed to its antioxidant activity and well presence of flavonoids.

PMID- 25972725
TI  - The Incidence of Central Line-Associated Bacteremia After the Introduction of
      Midline Catheters in a Ventilator Unit Population.
AB  - HYPOTHESIS: Our objective was to evaluate whether the use of midline venous
      catheters in place of central line venous catheters, when appropriate, decreased
      the overall incidence of central line-associated bacteremia in a ventilator unit.
      METHODS: The time interval between February 2012 and February 2013 was divided
      into 2 periods. Group A was the first half of the year, before the introduction
      of midline catheters, and group B was the second half of the year, 6 months after
      their introduction. Central line-associated bloodstream infection (CLABSI) was
      calculated using the equation: (total number of CLABSI/total number of catheter
      days) * 1000. The Z test was used for proportions between independent groups to
      compare the significance in the difference in CLABSI between groups A and B.
      RESULTS: There was a significant decrease in the total number of catheter days on
      the ventilator unit in group A from 2408 catheter days in 1 year (August 1, 2011,
      to July 31, 2012) before the introduction of midline catheters to 1521 catheter
      days in group B in the following year (November 1, 2012, to October 31, 2013; P <
      0.05 for both groups). CONCLUSIONS: Midline catheters in place of central lines
      decrease the rate of CLABSI in a ventilator unit. In addition, no bloodstream
      infections were associated with midline catheters.

PMID- 25972726
TI  - A Model for Creating a Supportive Trauma-Informed Culture for Children in
      Preschool Settings.
AB  - The all too common exposure of young children to traumatic situations and the
      life-long consequences that can result underscore the need for effective,
      developmentally appropriate interventions that address complex trauma. This paper
      describes Head Start Trauma Smart (HSTS), an early education/mental health cross
      systems partnership designed to work within the child's natural setting-in this
      case, Head Start classrooms. The goal of HSTS is to decrease the stress of
      chronic trauma, foster age-appropriate social and cognitive development, and
      create an integrated, trauma-informed culture for young children, parents, and
      staff. Created from a community perspective, the HSTS program emphasizes tools
      and skills that can be applied in everyday settings, thereby providing resources
      to address current and future trauma. Program evaluation findings indicate
      preliminary support for both the need for identification and intervention and the
      potential to positively impact key outcomes.

PMID- 25972727
TI  - High performance in silico virtual drug screening on many-core processors.
AB  - Drug screening is an important part of the drug development pipeline for the
      pharmaceutical industry. Traditional, lab-based methods are increasingly being
      augmented with computational methods, ranging from simple molecular similarity
      searches through more complex pharmacophore matching to more computationally
      intensive approaches, such as molecular docking. The latter simulates the binding
      of drug molecules to their targets, typically protein molecules. In this work, we
      describe BUDE, the Bristol University Docking Engine, which has been ported to
      the OpenCL industry standard parallel programming language in order to exploit
      the performance of modern many-core processors. Our highly optimized OpenCL
      implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or
      46% of peak performance. BUDE also exploits OpenCL to deliver effective
      performance portability across a broad spectrum of different computer
      architectures from different vendors, including GPUs from Nvidia and AMD, Intel's
      Xeon Phi and multi-core CPUs with SIMD instruction sets.

PMID- 25972728
TI  - Pathway-based Biomarkers for Breast Cancer in Proteomics.
AB  - Genes do not function alone but through complex biological pathways. Pathway
      based biomarkers may be a reliable diagnostic tool for early detection of breast
      cancer due to the fact that breast cancer is not a single homogeneous disease. We
      applied Integrated Pathway Analysis Database (IPAD) and Gene Set Enrichment
      Analysis (GSEA) approaches to the study of pathway-based biomarker discovery
      problem in breast cancer proteomics. Our strategy for identifying and analyzing
      pathway-based biomarkers are threefold. Firstly, we performed pathway analysis
      with IPAD to build the gene set database. Secondly, we ran GSEA to identify 16
      pathway-based biomarkers. Lastly, we built a Support Vector Machine model with
      three-way data split and fivefold cross-validation to validate the biomarkers.
      The approach-unraveling the intricate pathways, networks, and functional contexts
      in which genes or proteins function-is essential to the understanding molecular
      mechanisms of pathway-based biomarkers in breast cancer. 

PMID- 25972729
TI  - Role of Probiotics in health improvement, infection control and disease treatment
      and management.
AB  - Research which concerns the usefulness of Probiotics show increasing interest
      based on the rise of their publications, products and the awareness of the public
      of their benefits. There is increasing interest concerning Probiotics from the
      public, researchers, governmental organizations (such as the WHO/FAO) and
      medicinal and food companies. Probiotics means "let good microbes work for you in
      different fields get their benefits and take a rest". Such work will include,
      food digestion, production of useful products to destroy the bad microbes,
      complement the functions of the missed digestive enzymes (due to missed or
      defective genes), and to maintain the digestive system's pH, and so on.
      Probiotics will augment the efficiency of our biological fermentors, the
      digestive system. Many authors have described the history and the progress of
      Probiotics and their different applications. In this review, we will focus mainly
      on three points, health improvement, infection control and disease management,
      which could be eliminated by the use of different types of direct uses of
      Probiotics or by the use of foods containing Probiotics. 

PMID- 25972731
TI  - Adverse Drug Reactions and quality deviations monitored by spontaneous reports.
AB  - OBJECTIVES: The aim of this study was to determine the frequency and profile of
      spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a
      Brazilian teaching hospital and propose a consistent classification to study
      quality deviations. METHODS: This is a descriptive and retrospective study
      involving the analysis of spontaneous reports of ADRs and quality deviations in
      2010. ADRs were classified according to the reaction mechanism, severity, and
      causality. The drugs were classified according to their therapeutic classes and
      symptoms according to the affected organ. The quality deviations were classified
      according to the type of deviation and type of medicine available in the
      Brazilian market. RESULTS: A total of 68 forms were examined; ADRs accounted for
      39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs
      occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was
      the most affected organ, while anti-infectives (40.7%) were the therapeutic class
      that caused the most ADRs. The most common ADRs were type B (74.0%), moderates
      (37.0%), and probables (55.6%). In relation to quality deviations, the most
      frequent notifications were breaks, splits and leaks (20.9%) and related to
      generic drugs (43.9%). CONCLUSION: The classification system to study quality
      deviations was clear and consistent. This study demonstrated that practices and
      public policies related to more effective pharmacovigilance need to be
      implemented so that the number of spontaneous reports increases.

PMID- 25972733
TI  - Factors influencing community pharmacist decision to dispense generic or branded
      medicines; Eastern Province, Alahsa, Saudi Arabia.
AB  - BACKGROUND: Rising costs of medicines have increased the interest of policy
      makers in generic medicines. However, consumers' and health care providers'
      perception and attitude towards generic medicine act as a main barrier to the
      promotion of generic medicines. OBJECTIVE: To explore the factors community
      pharmacists consider while dispensing branded or generic medicines to consumers.
      METHOD: A qualitative study was planned; twenty community pharmacists (ten
      hospital affiliated pharmacies and ten non-hospital affiliated pharmacies) were
      approached using a convenient sampling method. Interviews were recorded and later
      were coded into themes. RESULT: Overall, it is seen that generic medicine stock
      was available for antibiotics, pain killers, cough syrups, antihistaminics and
      antacids. Pharmacists working in hospital affiliated pharmacies were more
      concerned about the quality of drug before dispensing it to the consumer and they
      believe that what is prescribed is best for them and substitution or switching is
      unnecessary while for pharmacists in the non-hospital affiliated pharmacies,
      appearance of the client was found to be the main factor influencing them to
      dispense generic (low cost) or branded (expensive) medicines. CONCLUSION:
      Physical appearance of the consumer is revealed to be one of the main factors
      affecting the pharmacist decision to dispense generic or branded medicine.
      Pharmacists practising in hospital affiliated pharmacies were found to be
      influenced by physicians' recommendation, and prefer to dispense good quality
      medicines.

PMID- 25972732
TI  - Comparative evaluation of metered-dose inhaler technique demonstration among
      community pharmacists in Al Qassim and Al-Ahsa region, Saudi-Arabia.
AB  - TITLE: Comparative evaluation of metered-dose inhaler technique demonstration
      among community pharmacists in Al Qassim and Al Ahsa regions, Saudi Arabia.
      BACKGROUND: Patients rely on the information about use of proper inhaler
      technique when dispensed by community pharmacists however; several studies have
      shown that patients are unable to show correct inhalation technique. The aim of
      this study is to assess the ability of community pharmacists in Al Qassim region
      to demonstrate proper inhalation technique of metered dose inhaler and compare
      the baseline outcomes with a similar study at Al-Ahsa region. METHOD: We approach
      96 pharmacies in Al Qassim region as mock patient (Investigator). The
      investigator asks the Pharmacist to guide him about proper inhalation technique
      of metered dose inhaler. Investigator completes a standardized and validated
      checklist of 8 steps of inhaler device use immediately after leaving the
      pharmacy. Baseline data were compared between the two study groups et al. Ahsa
      and Al-Qassim for variables for effectiveness of pharmacist handling of patient
      queries. RESULT: A total number of 96 community pharmacies were approached in
      five cities of the Al Qassim province in Saudi Arabia This study has found that
      majority (93.7%) of community pharmacists failed to demonstrate proper inhalation
      technique of pMDI inhaler. CONCLUSION: The pharmacists demonstrated particularly
      poor skills involving steps for coordination of the actuation process with the
      mechanics of inhalation with MDI. The errors detected in this simple assessment
      session, if translated to patient self-medication errors, are potentially
      significant.

PMID- 25972734
TI  - Pharmacist's knowledge, practice and attitudes toward pharmacovigilance and
      adverse drug reactions reporting process.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are a major cause of drug related
      morbidity and mortality. Pharmacovigilance is the science that plays an essential
      role in the reduction of ADRs, thus the evolution and growth of this science are
      critical for effective and safe clinical practice. OBJECTIVES: This study is
      considered the first study in the region to evaluate pharmacist's knowledge,
      practice and attitudes toward ADRs reporting after establishing the national ADRs
      reporting center in Jordan. METHOD: A cross sectional study was used to evaluate
      pharmacist knowledge and attitude toward ADRs reporting. A structured validated
      questionnaire was developed for this purpose and a total of 208 pharmacists were
      recruited to participate in this study. RESULTS: The majority of pharmacists have
      insufficient awareness and lack of knowledge about pharmacovigilance and ADRs
      reporting. Also the rate of reporting of ADRs was extremely poor. Several factors
      were found to discourage pharmacists from reporting ADRs, which include
      inadequate information available from the patient, unavailability of pharmacist
      ADRs form when needed, unawareness of the existence of the national ADRs
      reporting system. Also pharmacists think that ADRs are unimportant or they did
      not know how to report them. CONCLUSION: The results of this study suggest that
      pharmacists have insufficient knowledge about the concept of pharmacovigilance
      and spontaneous ADRs reporting. On the other hand, pharmacists had positive
      attitudes toward pharmacovigilance, despite their little experience with ADRs
      reporting. Educational programs are needed to increase pharmacist's role in the
      reporting process, and thus to have a positive impact on the overall patient
      caring process.

PMID- 25972735
TI  - Knowledge and awareness of adverse drug reactions and pharmacovigilance practices
      among healthcare professionals in Al-Madinah Al-Munawwarah, Kingdom of Saudi
      Arabia.
AB  - Adverse Drug Reactions (ADRs) are scantly reported with poor contribution by
      healthcare professionals worldwide and in particular in developing countries. The
      aim of this study was to assess the knowledge and awareness of adverse drug
      reactions (ADRs) reporting and pharmacovigilance system among healthcare
      professionals in Al-Madinah Al-Munawwarah hospitals, Kingdom of Saudi Arabia. A
      questionnaire was designed addressing; awareness of ADRs, knowledge of
      pharmacovigilance system, availability of ADRs reporting system, patient
      counseling about ADRs and documentation of ADRs. The questionnaire was
      distributed to randomly selected healthcare professionals (n = 585) such as
      physicians, pharmacists, nurses and pharmacists' technicians of hospitals.
      Completed questionnaires were collected and data were analyzed. Data were
      expressed in number as well as percentage. Of the 585 questionnaires circulated,
      a total of 384 healthcare professionals responded. Healthcare professional
      categories involved in the study were 148 physicians, 37 pharmacists, 158 nurses
      and 41 pharmacist technicians. The percent of the respondents who accepted to
      enroll in the study was 65.64%. Most of the respondents were unable to correctly
      define the pharmacovigilance term, but they were aware of ADRs. The awareness
      among healthcare professionals of the national pharmacovigilance system was
      39.6%. Pharmacists had a good knowledge of pharmacovigilance and ADRs terminology
      and showed a more positive attitude to report ADRs. A greater number of the
      healthcare professionals were aware of ADRs reporting, but practically it is not
      implemented in hospitals. Most hospitals had follow-up documentation systems, but
      did not include ADRs reporting. There was no distinct pharmacovigilance system in
      place. Our study has demonstrated a lack of knowledge and awareness of
      pharmacovigilance and ADRs reporting among healthcare professionals in hospitals.
      The poor knowledge of ADRs reporting emphasized the urgent need to implement the
      appropriate strategies to improve the awareness of pharmacovigilance practices
      and ADRs reporting in Al-Madinah Al-Munawwarah hospitals. 

PMID- 25972730
TI  - Targeting G protein coupled receptor-related pathways as emerging molecular
      therapies.
AB  - G protein coupled receptors (GPCRs) represent the most important targets in
      modern pharmacology because of the different functions they mediate, especially
      within brain and peripheral nervous system, and also because of their functional
      and stereochemical properties. In this paper, we illustrate, via a variety of
      examples, novel advances about the GPCR-related molecules that have been shown to
      play diverse roles in GPCR pathways and in pathophysiological phenomena. We have
      exemplified how those GPCRs' pathways are, or might constitute, potential targets
      for different drugs either to stimulate, modify, regulate or inhibit the cellular
      mechanisms that are hypothesized to govern some pathologic, physiologic, biologic
      and cellular or molecular aspects both in vivo and in vitro. Therefore,
      influencing such pathways will, undoubtedly, lead to different therapeutical
      applications based on the related pharmacological implications. Furthermore, such
      new properties can be applied in different fields. In addition to offering
      fruitful directions for future researches, we hope the reviewed data, together
      with the elements found within the cited references, will inspire clinicians and
      researchers devoted to the studies on GPCR's properties. 

PMID- 25972737
TI  - Determination and characterization of metronidazole-kaolin interaction.
AB  - The needs for safe, therapeutically effective antidiarrheal combination
      continuously lead to effective treatment. When administered simultaneously,
      metronidazole-kaolin interactions have been reported by FDA but not studied. This
      paper is the first to study metronidazole-kaolin interactions. Adsorption
      isotherms of a metronidazole-kaolin antidiarrheal combination from aqueous
      solutions at an in vivo simulated pH conditions were obtained at 37 +/- 0.5 
      degrees C. Langmuir constants for the adsorption are 10.8225, 41.3223 mg g(-1)
      and 11.60, 2.56 l g(-1) aimed at the monolayer capacity, and the equilibrium
      constant at pH 1.2 and 6.8, respectively. pH effect on adsorption of known
      concentration of metronidazole by kaolin was also studied over the range 1.2-8. A
      gradual increase in the adsorbed amount was noted with increasing the pH. Elution
      studies by different eluents showed that drug recovery from adsorbent surface was
      pH-dependent via competitive mechanism. The elution followed the sequence: 0.1 M
      HCl > 0.1 M NaCl > H2O. Adsorption-desorption studies revealed physical
      adsorption. The equilibrium concentration of metronidazole decreased as the
      adsorbent concentration was increased in the systems. The dissolution profiles
      (USP) of commercially available tablets (Riazole(r) 500 mg) were obtained alone
      and in the presence of either (ORS(r)) rehydration salts and 9 or 18 g of kaolin
      powder. The percentage drug released versus time: 95.01% in 25 min, 101.02% in 30
      min, 67.63% in 60 min, 60.59% in 60 min, respectively. The percentage drug
      released versus time was increased with ORS(r) due to common ion effect [Cl(-)],
      while, it was decreased with kaolin due to adsorption. The mechanism of reaction
      of Riazole(r) (500 mg) tablets in the different dissolution media, confirms with
      Korsmeyer-Peppas model. The interaction between metronidazole and kaolin was
      characterized by melting point determinations, differential scanning calorimetry
      analysis and infrared spectroscopy. The results obtained were suggestive of
      physical interaction between metronidazole and kaolin. 

PMID- 25972736
TI  - Refining knowledge, attitude and practice of evidence-based medicine (EBM) among
      pharmacy students for professional challenges.
AB  - Practicing evidence based medicine (EBM) is a professional need for the future
      clinical pharmacist in UAE and around the world. An attempt was made to evaluate
      pharmacy student's knowledge, attitude and proficiency in the practice of EBM. A
      within-subject study design with pre and post survey and skill test were
      conducted using case based practice of EBM through a validated questionnaire. The
      results were tabulated and there was a statistically significant increase in
      pharmacy students' perceived ability to go through steps of EBM, namely:
      formulating PICO questions (95.3%), searching for evidence (97%), appraising the
      evidence (81%), understanding statistics (78.1%), and applying evidence at point
      of care (81.2%). In this study, workshops and (Problem Based Learning) PBLs were
      used as a module of EBM teaching and practices, which has been shown to be an
      effective educational method in terms of improving students' skills, knowledge
      and attitude toward EBM. Incorporating hands on experience, PBLs will become an
      impetus for developing EBM skills and critical appraisal of research evidence
      alongside routine clinical practice. This integration would constitute the
      cornerstone in lifting EBM in UAE up to the needed standards and would enable
      pharmacy students to become efficient pharmacists that rely on evidence in their
      health practice. 

PMID- 25972738
TI  - The effect of pioglitazone on pharmacokinetics of carbamazepine in healthy
      rabbits.
AB  - INTRODUCTION: Drug-drug interactions can lead to serious and potentially lethal
      adverse events. In recent years, several drugs have been withdrawn from the
      market due to interaction-related adverse events. The objective of this study was
      to evaluate the pharmacokinetic interaction between pioglitazone (PG) and
      carbamazepine (CBZ) in healthy male rabbits. METHODS: A randomized, two-crossover
      design study was conducted in six healthy male rabbits. The study consisted of
      two periods: period one, when each rabbit received a single dose of 70 mg CBZ
      suspension. Period two, when each rabbit received a single dose of 70 mg CBZ
      suspension co-administered with a single dose of 1.5 mg PG with a washout period
      of one week between the two periods. Serial blood samples were collected over a
      period of 48 h. Chemiluminescent enzyme immunoassay (CLEIA) was used to measure
      CBZ in serum. Pharmacokinetic (PK) parameters Cmax, Tmax, t 1/2, AUC0-t, AUC 0
      infinity, and ke were determined for the two periods using non-compartmental
      analysis. RESULTS: In the two periods of treatment, Cmax, Tmax, AUC0-t, AUC0
      infinity, t 1/2 and ke for CBZ were administered alone and in combination with
      PG. Cmax, the mean peak plasma concentration was 4.33 +/- 2.4 MUg/mL versus 4.76
      +/- 2.1 MUg/ml, tmax, time taken to reach, was 2.91 +/- 1.11 h versus 3.6 +/-
      1.83 h, total area under the curve AUC0-t was 64.90 +/- 43.6 MUg.h/ml versus
      102.90 +/- 66.9 MUg.h/ml, AUC0-infinity was 74.0 +/- 52.6 MUg.h/ml versus 124.3
      +/- 85 MUg.h/mL, t 1/2 was 14.10 +/- 2.5 h versus 16.43 +/- 6.43 h and
      elimination rate constant ke was 0.050 +/- 0.009 h(-1) versus 0.057 +/- 0.049 h(
      1), respectively. No statistical differences were found in pharmacokinetic of CBZ
      in both cases (P > 0.05). CONCLUSION: The result of the study demonstrated that
      PG does not affect pharmacokinetic parameters of CBZ. Therefore, no cautions
      regarding dose or administration pattern of CBZ with PG should be taken.

PMID- 25972739
TI  - Ehrlich tumor inhibition using doxorubicin containing liposomes.
AB  - Ehrlich tumors were grown in female balb mice by subcutaneous injection of
      Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with
      saline, DOX in solution or DOX encapsulated within liposomes prepared from
      DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed
      that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor
      growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All
      the DOX formulations were effective in preventing tumor growth compared to
      saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in
      tumor growth than treatment with DOX only. Histopathological examination of the
      entire tumor sections for the various groups revealed marked differences in
      cellular features accompanied by varying degrees in necrosis percentage ranging
      from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The
      proposed liposomal formulation can efficiently deliver the drug into the tumor
      cells by endocytosis (or passive diffusion) and lead to a high concentration of
      DOX in the tumor cells. The study showed that the formulation of liposomal
      doxorubicin improved the therapeutic index of DOX and had increased anti-tumor
      activity against Ehrlich tumor models. 

PMID- 25972740
TI  - Cationic nanoemulsions as potential carriers for intracellular delivery.
AB  - Successful cytosolic delivery enables opportunities for improved treatment of
      various genetic disorders, infectious diseases and cancer. Cationic nanoemulsions
      were designed using alternative excipients and evaluated for particle size,
      charge, effect of sterilization on its stability, DNA condensation potential and
      cellular uptake efficiency. Various concentrations of non-ionic and ionic
      stabilizers were evaluated to design formula for colloidally stable cationic
      nanoemulsion. The nanoemulsion comprised of 5% Capmul MCM, 0.5%
      didodecyldimethylammonium bromide (DDAB), 1% phospholipid, 1% Poloxamer 188 and
      2.25% glycerol and possessed particle size of 81.6 +/- 3.56 nm and 137.1 +/- 1.57
      nm before and after steam sterilization, respectively. DNA condensation studies
      were carried out at various nanoemulsion: DNA ratios ranging from 1:1 to 10:1.
      Cell uptake studies were conducted on human embryonic kidney (HEK) cell lines
      which are widely reported for transfection studies. The nanoemulsions showed
      excellent cellular uptake as evaluated by fluorescence microscopy and flow
      cytometry. Overall, a colloidally stable cationic nanoemulsion with good DNA
      condensation ability was successfully fabricated for efficient cytosolic delivery
      and potential for in vivo effectiveness. 

PMID- 25972741
TI  - Effect of different polymers on in vitro and ex vivo permeability of Ofloxacin
      from its mucoadhesive suspensions.
AB  - Considering the importance of drug permeation from formulations, in vitro and ex
      vivo drug permeation characteristics of three oral mucoadhesive suspensions of
      Ofloxacin were designed and compared. Three suspensions of Ofloxacin were
      prepared by taking two grades of Carbopol polymer such as Carbopol 934 (C934) and
      Carbopol 940 (C940); and Hydroxypropyl methylcellulose. The permeability study
      was performed by using a Franz diffusion cell through both synthetic cellulose
      acetate membrane and excised goat gastrointestinal membranes in acidic as well as
      alkaline pH. To know the permeability of the drug from control/formulations
      through different membranes in acidic/alkaline pH, cumulative percentage drug
      permeation, apparent permeability (Papp) and flux (J) were calculated. In
      addition, enhancement ratio (ER) of each formulation was also determined. From
      our results, it is evident that formulation containing C940 was the best
      suspension considering Papp and J values of all formulations. Moreover, it was
      the most beneficial formulation for improving permeation and diffusivity of
      Ofloxacin even after 16 h. Hence, this suspension was probably the most suitable
      formulation to obtain prolonged release action of the drug. The ER values of all
      formulations through the excised goat intestinal mucus membrane in alkaline pH
      were higher than those formulations through the goat stomach mucosal membrane in
      acidic pH. ER values of those formulations indicate that the permeability of the
      drug was more enhanced by the polymers in the intestinal part, leading to more
      bioavailability and prolonged action in that portion of the gastrointestinal
      tract. It may also be concluded from our results that in addition to formulation
      containing C940, other formulations may also show effective controlled release
      action. 

PMID- 25972742
TI  - Design, synthesis and antibacterial potential of 5-(benzo[d][1,3]dioxol-5-yl)-3
      tert-butyl-1-substituted-4,5-dihydropyrazoles.
AB  - A series of 5-(benzo[d][1,3]dioxol-5-yl)-3-tert-butyl-1-substituted-4,5
      dihydropyrazole derivatives 4a-e and 6a-g have been synthesized and spectrally
      characterized. The antibacterial activity of the novel candidates has been
      screened using the agar diffusion test. These compounds were endowed with high
      antibacterial activity against different Gram +ve and Gram -ve bacteria when
      compared with standard antibacterial drugs. In the light of zone of inhibition
      and MIC results, Sarcina and Staphylococcus aureus are the most sensitive
      bacteria where pyrrolidinomethanone derivative 4e showed MICs at 80 and 110 nM,
      respectively. While hydroxypiperidinoethanone derivative 6c showed MIC at 90 nM
      for Sarcina. 

PMID- 25972743
TI  - Pilot testing of a pharmacist led care program for asthma patients in Saudi
      Arabia.
AB  - This study aimed at evaluating the usefulness of a structured patient counseling
      program on clinical outcomes of asthma patients in Saudi Arabia. This cross
      sectional study enrolled 10 asthma patients and all were evaluated for their
      baseline knowledge on asthma, quality of life, compliance, patient satisfaction
      and drug related problems among randomly selected 5 (of the total 10) patients.
      The median (IQR) age of the patients was 46 (33.5-56.2) years. The baseline
      knowledge scores was 9 (8-11), the maximum possible scores to be 21. Cronbach
      alpha of the KQ was 0.65. The overall total median (IQR) compliance (Morisky)
      score was 4 (3-5), the maximum possible score was 5. The patient satisfaction
      median (IQR) score was 35.5 (32-46.25), the maximum possible score was 70. Of the
      total patients 3 (30%) had a history of allergy. There were total 18 allergens
      observed in these patients. There has been no drug-drug or drug-food interactions
      observed between among the prescribed drugs of the patients. Altogether 2
      patients reported a total of 2 ADRs. The knowledge of the asthma patients was
      found to be poor. Missing the dose was the most commonly encountered drug taking
      behavior. The compliance was found to be good and the patient satisfaction was
      average. 

PMID- 25972744
TI  - Screening of mitochondrial mutations and insertion-deletion polymorphism in
      gestational diabetes mellitus in the Asian Indian population.
AB  - In this study we scrutinized the association between the A8344G/A3243G mutations
      and a 9-bp deletion polymorphism with gestational diabetes mellitus (GDM) in an
      Asian Indian population. The A3243G mutation in the mitochondrial tRNA(Leu(UUR))
      causes mitochondrial encephalopathy myopathy, lactic acidosis, and stroke-like
      episodes (MELAS), while the A8344G mutation in tRNA(Lys) causes myoclonus
      epilepsy with ragged red fibers (MERRF). We screened 140 pregnant women diagnosed
      with GDM and 140 non-GDM participants for these mutations by PCR-RFLP analysis.
      Both A3243G and A8344G were associated with GDM (A3243: OR-3.667, 95% CI = 1.001
      13.43, p = 0.03; A8344G: OR-11.00, 95% CI = 0.6026-200.8, p = 0.04).
      Mitochondrial DNA mutations contribute to the development of GDM. Our results
      conclude that mitochondrial mutations are associated with the GDM women in our
      population. Thus it is important to screen other mitochondrial mutations in the
      GDM women. 

PMID- 25972745
TI  - Bioconcentration of some macrominerals in soil, forage and buffalo hair
      continuum: A case study on pasture irrigated with sewage water.
AB  - The present study aimed to evaluate the bioaccumulation of some macrominerals in
      grazing buffaloes fed forage irrigated with sewage water or canal water. In
      particular, the transfer of sodium (Na), magnesium (Mg), potassium (K) and
      calcium (Ca) from soil to plant and in turn to animals was evaluated under sub
      tropical environmental conditions. Samples of soil, forage and buffalo hair were
      collected and digested by wet method. Sodium and K concentrations were
      significantly higher in the soil but lower in the forages; however, Mg and Ca
      concentrations in both soil and forages were higher. The correlation between
      soil, forage and hair showed an imbalanced flow of Na, Mg and K and a balanced
      flow of Ca from soil to forage and then to animals. Based on the findings, the
      highest rates of transfer of minerals were found for sewage water treatment,
      whereas lowest rates were found for canal water treatment, except for Na. As the
      transfer of minerals depends on their bioavailability, the highest values may be
      due to the high rates of mineral uptake by plants. Thus, the high transfer rate
      of some elements by plants could become toxic in future causing detrimental
      effect to grazing livestock. 

PMID- 25972746
TI  - Improvement of antioxidant and defense properties of Tomato (var. Pusa Rohini) by
      application of bioaugmented compost.
AB  - Nutrient management practices play a significant role in improving the
      nutritional quality of tomato. The present study deals with the evaluation of
      compost prepared using Effective Microorganisms (EM), on antioxidant and defense
      enzyme activities of Tomato (Lycopersicon esculentum). A field experiment with
      five treatments (control, chemical fertilizer and EM compost alone and in
      combination) was conducted in randomized block design. An increment of 31.83% in
      tomato yield was recorded with the combined use of EM compost and half
      recommended dose of chemical fertilizers (N50P30K25 + EM compost at the rate of 5
      t ha(-1)). Similarly, fruit quality was improved in terms of lycopene content
      (35.52%), antioxidant activity (24-63%) and defense enzymes activity (11-54%), in
      tomatoes in this treatment as compared to the application of recommended dose of
      fertilizers. Soil microbiological parameters also exhibited an increase of 7-31%
      in the enzyme activities in this treatment. Significant correlation among fruit
      quality parameters with soil microbiological activities reveals the positive
      impact of EM compost which may be adopted as an eco-friendly strategy for
      production of high quality edible products. 

PMID- 25972747
TI  - Update of ichthyofauna diversity and ecological status of a coastal River Nero
      (Cote d'Ivoire - West Africa).
AB  - The general aim of this study is to update the inventory of the fish species and
      to specify distribution patterns in the Nero River ichthyofauna in order to
      establish some basis for the conservation of these fish communities and their
      habitat. From February 2009 to January 2010, thirty-three sites were sampled
      monthly with gill nets and a backpack electrofisher, and environmental variables
      were recorded. Overall, 46 species included in 33 genuses, 24 families and 9
      orders were collected. Eleven families and 30 species were the first records for
      the Nero River. Including all species previously listed in the literature, the
      number of species presently known in the Nero River and its tributaries is
      revised to 59. Four families, Alestidae (21%), Schilbeidae (19%), Cyprinidae
      (17%) and Cichlidae (16%) that made up 73% of the total number of the catches,
      were the most dominant. The most dominant numerical species were Schilbe
      mandibularis and Brycinus longipinnis. Fish species and sampling sites along with
      eight environmental variables were ordinated with canonical correspondence
      analysis (CCA) coupled to the Monte Carlo test. Ecological status based on fish
      assemblage according to environmental variables and anthropogenic pressures
      showed that miss dead wood leaves and roots, electrical conductivity, total
      dissolved solids, mud, nitrite, basin width, dissolved oxygen and pH, were the
      primary factors influencing fish distribution. The environmental tolerance index
      (ETI), ecological tolerance (tk ) and optima (uk ) values of 10 species to 8
      different environmental variables were analyzed. Six species (Hemichromis
      fasciatus, Epiplatys chaperi, Barbus ablabes, B. longipinnis, Hemichromis
      bimaculatus and Chromidotilapia guntheri) have high ETI and a cosmopolitan
      distribution in the Nero River. In the tributaries of the middle course, high
      concentrations of nitrite in the water, added to the presence of a lot of
      tolerant species in the ichthyofauna are indications of disturbance of these
      areas. Subsequent recommendations were formulated for efficient restoration and
      conservation management of this River. 

PMID- 25972748
TI  - Enhancing growth performance and systemic acquired resistance of medicinal plant
      Sesbania sesban (L.) Merr using arbuscular mycorrhizal fungi under salt stress.
AB  - Pot experiments were conducted to evaluate the damaging effects of salinity on
      Sesbania sesban plants in the presence and absence of arbuscular mycorrhizal
      fungi (AMF). The selected morphological, physiological and biochemical parameters
      of S. sesban were measured. Salinity reduced growth and chlorophyll content
      drastically while as AMF inoculated plants improved growth. A decrease in the
      number of nodules, nodule weight and nitrogenase activity was also evident due to
      salinity stress causing reduction in nitrogen fixation and assimilation
      potential. AMF inoculation increased these parameters and also ameliorated the
      salinity stress to some extent. Antioxidant enzymes like superoxide dismutase
      (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR)
      as well as non enzymatic antioxidants (ascorbic acid and glutathione) also
      exhibited great variation with salinity treatment. Salinity caused great
      alterations in the endogenous levels of growth hormones with abscisic acid
      showing increment. AMF inoculated plants maintained higher levels of growth
      hormones and also allayed the negative impact of salinity. 

PMID- 25972749
TI  - Effect of grapeseed oil on diazinon-induced physiological and histopathological
      alterations in rats.
AB  - The pollution of environment by toxic chemicals is a global and chronic problem.
      Human health risk due to exposure to chemical pollutants is constantly
      increasing. Pesticides form major toxic chemicals in environment. Scientifically,
      there is an obviously correlation between the exposure to pesticides and
      appearance of many diseases. Currently, the significance of natural products for
      health and medicine has been formidable. The present study investigated the
      effect of grapeseed oil in male rats exposed to diazinon. The experimental rats
      were divided into five groups. The rats of the first group were served as
      control. The experimental animals of the second group were exposed to diazinon
      (DZN). The animals of the third group were supplemented with grapeseed oil and
      treated with DZN. The rats of the fourth group were supplemented with grapeseed
      oil. The experimental rats of the fifth group were supplemented with corn oil.
      Hematobiochemical and histopathological evaluations were chosen as indicators of
      DZN toxicity and protective role of grapeseed oil. In rats exposed only to DZN,
      the levels of serum glucose, triglycerides, cholesterol, low density lipoprotein
      cholesterol, very low density lipoprotein cholesterol, creatinine, urea nitrogen,
      uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline
      phosphatase, creatine kinase and lactate dehydrogenase were statistically
      increased, while the level of serum total protein was significantly decreased.
      Moreover, the histopathological evaluations of the liver, kidney and testis
      showed that DZN causes several severe alterations. Pretreatment with grapeseed
      oil exhibited a protective role against DZN toxicity which confirmed by the
      inhibition of hematobiochemical and histopathological changes due to DZN
      exposure. Additionally, the present study suggests that the effect of grapeseed
      oil supplementation against DZN toxicity may be attributed to the antioxidant
      role of its constituents. 

PMID- 25972750
TI  - Evaluation of in-vitro antioxidant and antibacterial properties of Commelina
      nudiflora L. extracts prepared by different polar solvents.
AB  - The study explored on the commonly available weed plant Commelina nudiflora which
      has potential in-vitro antioxidant and antimicrobial activity. The different
      polar solvents such as ethanol, chloroform, dichloromethane, hexane and aqueous
      were used for the soxhlet extraction. The extracts were identified
      pharmacologically as important bioactive compounds and their potential free
      radical scavenging activities, and antimicrobial properties were studied. C.
      nudiflora extracts were monitored on their in-vitro antioxidant ability by DPPH
      and ABTS radical scavenging assay. Aqueous extract shows significant free radical
      scavenging activity of 63.4 mg/GAE and 49.10 mg/g in DPPH and ABTS respectively.
      Furthermore, the aqueous crude extract was used in antibacterial studies, which
      shows the highest inhibitory activity against Pseudomonas aeruginosa, Escherichia
      coli and Salmonella typhi. Among all the extracts, aqueous extract of C.
      nudiflora has significant control over free radical scavenging activity and
      inhibition of the growth of food pathogenic bacteria. Also, the aqueous extract
      contains abundance of phenolics and flavonoids higher than other extracts. This
      study explored weed plant C. nudiflora as a potential source of antioxidant and
      antibacterial efficacy and identified various therapeutic value bioactive
      compounds from GC-MS analysis. 

PMID- 25972751
TI  - Histological, molecular and biochemical detection of renal injury after Echis
      pyramidum snake envenomation in rats.
AB  - Nephrotoxicity is a common sign of snake envenomation. The present work aimed to
      clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of
      Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from
      envenomation. Histopathological examination showed intense dose and time
      dependent abnormalities, including swelling glomerulus and tubular necrosis and
      damage as well as signs of intertubular medullary hemorrhage at early stages of
      envenomation. However, at late stages of envenomation by any of the doses under
      investigation, no intact renal corpuscles were recorded and complete lysis in
      renal corpuscles with ruptured Bowman's capsules was observed.
      Immunohistochemistry by immunohistochemical staining was used to test the protein
      expression of Bax in renal tissue of rats. The result showed that the expression
      of Bax in renal tissue sections of envenomated rats was increased according to
      dose and time-dependant manner. The isolation of DNA from the renal cells of
      envenomed rats pointed out to the occurrence of DNA fragmentation, which is
      another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E.
      pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and
      nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant
      capacity and catalase were assayed in renal tissue homogenates. The venom induced
      significant increase in the levels of malondialdehyde and nitrite/nitrate while
      the levels of glutathione, total antioxidant capacity and catalase were
      significantly decreased, especially after 6 h of envenomation. The results
      revealed that the E. pyramidum induced dose and time-dependant significant
      disturbances in the physiological parameters in the kidney. We conclude that the
      use of the immunohistochemical techniques, the detection of DNA integrity and
      oxidative stress marker estimations are more specific tools that can clarify
      cellular injury and could point out to the defense activity of the renal tissue
      at envenomation. 

PMID- 25972752
TI  - A new species of plasmodiidae (Coccidia: Hemosporidia) from the blood of the
      skink Scincus hemprichii (Scincidae: Reptilia) in Saudi Arabia.
AB  - Fallisia arabica n. sp. was described from peripheral blood smears of the Skink
      lizard, Scincus hemprichii from Jazan Province in the southwest of Saudi Arabia.
      Schizogony and gametogony take place within neutrophils in the peripheral blood
      of the host. Mature schizont is rosette shaped 17.5 +/- 4.1 * 17.0 +/- 3.9 MUm,
      with a L/W ratio of 1.03(1.02-1.05) MUm and produces 24(18-26) merozoites. Young
      gametocytes are ellipsoidal, 5.5 +/- 0.8 * 3.6 +/- 0.5 MUm, with a L/W of
      1.53(1.44-1.61) MUm. Mature macrogametocytes are ellipsoidal, 9.7 +/- 1.2 * 7.8
      +/- 1.0 MUm, with a L/W of 1.24(1.21-1.34) MUm and microgametocytes are
      ellipsoidal, 7.0 +/- 1.1 * 6.8 +/- 0.9 MUm. with a L/W of 1.03(1.01-1.10) MUm. In
      comparison to the described Fallisia species, this new taxon has rosette
      schizonts and is larger than F. dominicensis, in Hispaniola, F. bipocrati, F.
      poecilopi, in Panama, F. thecadactyli in Venezuela, and F. effusa, F. simplex, F.
      modesta, in Brazil. F. arabica has fewer merozoites than F. effusa, F. poecilopi,
      F. thecadactyli and F. siamense in Thailand. This new species has more merozoites
      than F. dominicensis and F. modesta. All of these species belong to diverse
      saurian families (Agamidae, Gekkonidae, Polychrotidae, Scincidae and Teiidae)
      parasitize only thrombocytes or lymphocytes and some species parasitize immature
      erythroid cells and leucocytes. 

PMID- 25972753
TI  - Post-exposure temperature influence on the toxicity of conventional and new
      chemistry insecticides to green lacewing Chrysoperla carnea (Stephens)
      (Neuroptera: Chrysopidae).
AB  - Chrysoperla carnea (Stephens) is an important biological control agent currently
      being used in many integrated pest management (IPM) programs to control insect
      pests. The effect of post-treatment temperature on insecticide toxicity of a
      spinosyn (spinosad), pyrethroid (lambda cyhalothrin), organophosphate
      (chlorpyrifos) and new chemistry (acetamiprid) to C. carnea larvae was
      investigated under laboratory conditions. Temperature coefficients of each
      insecticide tested were evaluated. From 20 to 40  degrees C, toxicity of lambda
      cyhalothrin and spinosad decreased by 2.15- and 1.87-fold while toxicity of
      acetamiprid and chlorpyrifos increased by 2.00 and 1.79-fold, respectively. The
      study demonstrates that pesticide effectiveness may vary according to
      environmental conditions. In cropping systems where multiple insecticide products
      are used, attention should be given to temperature variation as a key factor in
      making pest management strategies safer for biological control agents.
      Insecticides with a negative temperature coefficient may play a constructive role
      to conserve C. carnea populations. 

PMID- 25972754
TI  - Phytochemical, antioxidant and mineral composition of hydroalcoholic extract of
      chicory (Cichorium intybus L.) leaves.
AB  - The phytochemical, antioxidant and mineral composition of hydroalcoholic extract
      of leaves of Cichorium intybus L., was determined. The leaves were found to
      possess comparatively higher values of total flavonoids, total phenolic acids.
      The phytochemical screening confirmed the presence of tannins, saponins,
      flavonoids, in the leaves of the plant. The leaf extract was found to show
      comparatively low value of IC50 for 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      inhibition. The IC50 value of chicory leaves extract was found to be 67.2 +/- 2.6
      MUg/ml. The extracts were found to contain high amount of mineral elements
      especially Mg and Zn. Due to good phytochemical and antioxidant composition, C.
      intybus L., leaves would be an important candidate in pharmaceutical formulations
      and play an important role in improving the human health by participating in the
      antioxidant defense system against free radical generation. 

PMID- 25972755
TI  - Angiotensin converting enzyme gene polymorphism studies: A case-control study.
AB  - Mild gestational hyperglycemia (MGH) is a very common complication of pregnancy
      that is characterized by intolerance to glucose. The association of angiotensin
      converting enzyme (ACE) insertion/deletion (I/D) polymorphism to MGH has been
      previously reported. In this study, we evaluated the association between ACE
      polymorphism and the risk of MGH in a Saudi population. We conducted a case
      control study in a population of 100 MGH patients and 100 control subjects. ACE
      gene polymorphism was analyzed by the novel approach of tetraprimer amplification
      refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequency
      of ACE polymorphism was not associated with either alleles or genotypes in MGH
      patients. Glucose concentration was found to be significantly associated with the
      MGH group. Our study suggests that ACE genotypes were not associated with ACE
      polymorphism in a Saudi population. 

PMID- 25972756
TI  - Synthesis, spectroscopic and chromatographic studies of sunflower oil biodiesel
      using optimized base catalyzed methanolysis.
AB  - Methyl esters from vegetable oils have attracted a great deal of interest as
      substitute for petrodiesel to reduce dependence on imported petroleum and provide
      an alternate and sustainable source for fuel with more benign environmental
      properties. In the present study biodiesel was prepared from sunflower seed oil
      by transesterification by alkali-catalyzed methanolysis. The fuel properties of
      sunflower oil biodiesel were determined and discussed in the light of ASTM D6751
      standards for biodiesel. The sunflower oil biodiesel was chemically characterized
      with analytical techniques like FT-IR, and NMR ((1)H and (13)C). The chemical
      composition of sunflower oil biodiesel was determined by GC-MS. Various fatty
      acid methyl esters (FAMEs) were identified by retention time data and verified by
      mass fragmentation patterns. The percentage conversion of triglycerides to the
      corresponding methyl esters determined by (1)H NMR was 87.33% which was quite in
      good agreement with the practically observed yield of 85.1%. 

PMID- 25972757
TI  - Assessment of genetic diversity among faba bean genotypes using agro
      morphological and molecular markers.
AB  - Forty faba bean (Vicia faba L.) genotypes were evaluated for their agro
      morphological performance and molecular diversity under Central Region of Saudi
      Arabia conditions during 2010-11 and 2011-12 seasons. Field performance results
      showed that faba genotypes exhibited a significant amount of variation for their
      agro-morphological studied parameters. Giza40 recorded the tallest genotype
      (139.5 cm), highest number of seeds per plants (100.8), and the highest seed
      yield per plant (70.8 g). The best performing genotypes were Giza40, FLIP03
      014FB, Gazira1 and Goff1. Genetic variability among genotypes was determined
      using Sequence Related Amplified Polymorphism (SRAP) and Amplified Fragment
      Length Polymorphism (AFLP) markers. A total of 183 amplified fragments (alleles)
      and 1758 polymorphic fragments (bands) in SRAP and 202 alleles and 716 bands in
      AFLP were obtained using six SRAP and four AFLP primer combinations respectively.
      Polymorphism information content (PIC) values for AFLP and SRAP markers were
      higher than 0.8, indicating the existence of a considerable amount of genetic
      diversity among faba tested genotypes. The UPGMA based clustering of faba
      genotypes was largely based on origin and/or genetic background. Result of
      cluster analysis based on SRAP showed weak and not significant correlation while,
      it was highly significant based on AFLP analysis with agro-morphological
      characters (r = 0.01, p > 0.54 and r = 0.26, p < 0.004 respectively). Combined
      SRAP and AFLP markers proved to be significantly useful for genetic diversity
      assessment at molecular level. They exhibited high discrimination power, and were
      able to distinguish the faba bean genotypes with high efficiency and accuracy
      levels. 

PMID- 25972758
TI  - Reproductive biology of the horned viper, Cerastes cerastes gasperettii in the
      central region of Saudi Arabia.
AB  - The reproductive biology of the horned viper, Cerastes cerastes gasperettii, in
      Riyadh region of Saudi Arabia was investigated over a period of one year. Study
      of reproductive cycle of male and female C. c. gasperettii revealed that the
      breeding season is relatively short (April and May). Thereafter females laid eggs
      by mid of July and hatching probably had taken place by the end of September. No
      activity was observed during winter, this may indicate just a single clutch per
      year. Relative testis weight to body weight was drastically increased ([Formula:
      see text] = 0.88%) during the peak of reproductive activity (May) where maximal
      expansion of seminiferous tubules was also attained during April and May
      ([Formula: see text] = 209 MUm and 191 MUm, respectively). Likewise, the ovarian
      activity was the highest during May where ovarian parameters were greater in
      terms of relative ovarian weight to body weight and ova diameter being 0.46% and
      2.29 mm, respectively. Fat body weight was increased drastically just before the
      peak of reproductive activity then started to decline during June. It could be
      concluded that the harsh desert conditions and similar environments certainly
      affect reproductive activity of Saudi Arabian reptiles including snakes. 

PMID- 25972759
TI  - Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis.
AB  - Although cytotoxicity and endocytosis of nanoparticles have been the subject of
      numerous studies, investigations regarding exocytosis as an important mechanism
      to reduce intracellular nanoparticle accumulation are rather rare and there is a
      distinct lack of knowledge. The current study investigated the behavior of human
      microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles
      (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl
      beta-cyclodextrin (MbetacD)] and different analytical methods (flow cytometry,
      transmission electron microscopy, inductively coupled plasma mass spectrometry).
      Overall, it was found that endothelial cells were able to release CeO2
      nanoparticles via exocytosis after the migration of nanoparticle containing
      endosomes toward the plasma membrane. The exocytosis process occurred mainly by
      fusion of vesicular membranes with plasma membrane resulting in the discharge of
      vesicular content to extracellular environment. Nevertheless, it seems to be
      likely that nanoparticles present in the cytosol could leave the cells in a
      direct manner. MbetacD treatment led to the strongest inhibition of the
      nanoparticle exocytosis indicating a significant role of the plasma membrane
      cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to
      cell-surface-transport) caused a higher inhibitory effect on exocytosis than
      nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi
      compartments to the cell surface influenced the exocytosis process of the CeO2
      nanoparticles more than the microtubule-associated transport. In conclusion,
      endothelial cells, which came in contact with nanoparticles, e.g., after
      intravenously applied nano-based drugs, can regulate their intracellular
      nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on
      cells.

PMID- 25972761
TI  - [Formula: see text] rule, [Formula: see text] and [Formula: see text] in
      [Formula: see text] and [Formula: see text] models with FCNC quark couplings.
AB  - The experimental value for the isospin amplitude [Formula: see text] in [Formula:
      see text] decays has been successfully explained within the standard model (SM),
      both within the large [Formula: see text] approach to QCD and by QCD lattice
      calculations. On the other hand within the large [Formula: see text] approach the
      value of [Formula: see text] is by at least [Formula: see text] below the data.
      While this deficit could be the result of theoretical uncertainties in this
      approach and could be removed by future precise QCD lattice calculations, it
      cannot be excluded that the missing piece in [Formula: see text] comes from new
      physics (NP). We demonstrate that this deficit can be significantly softened by
      tree-level FCNC transitions mediated by a heavy colourless [Formula: see text]
      gauge boson with a flavour-violating left-handed coupling [Formula: see text] and
      an approximately universal flavour diagonal right-handed coupling [Formula: see
      text] to the quarks. The approximate flavour universality of the latter coupling
      assures negligible NP contributions to [Formula: see text]. This property,
      together with the breakdown of the GIM mechanisms at tree level, allows one to
      enhance significantly the contribution of the leading QCD-penguin operator
      [Formula: see text] to [Formula: see text]. A large fraction of the missing piece
      in the [Formula: see text] rule can be explained in this manner for [Formula: see
      text] in the reach of the LHC, while satisfying the constraints from [Formula:
      see text], [Formula: see text], [Formula: see text], LEP-II and the LHC. The
      presence of a small right-handed flavour-violating coupling [Formula: see text]
      and of enhanced matrix elements of [Formula: see text] left-right operators
      allows one to satisfy simultaneously the constraints from [Formula: see text] and
      [Formula: see text], although this requires some fine-tuning. We identify the
      quartic correlation between [Formula: see text] contributions to [Formula: see
      text], [Formula: see text], [Formula: see text] and [Formula: see text]. The
      tests of this proposal will require much improved evaluations of [Formula: see
      text] and [Formula: see text] within the SM, of [Formula: see text] as well as
      precise tree-level determinations of [Formula: see text] and [Formula: see text].
      We present correlations between [Formula: see text], [Formula: see text] and
      [Formula: see text] with and without the [Formula: see text] rule constraint and
      generalise the whole analysis to [Formula: see text] with colour ([Formula: see
      text]) and [Formula: see text] with FCNC couplings. In the latter case no
      improvement on [Formula: see text] can be achieved without destroying the
      agreement of the SM with the data on [Formula: see text]. Moreover, this scenario
      is very tightly constrained by [Formula: see text]. On the other hand, in the
      context of the [Formula: see text] rule [Formula: see text] is even more
      effective than [Formula: see text]: it provides the missing piece in [Formula:
      see text] for [Formula: see text]-[Formula: see text].

PMID- 25972763
TI  - Picturing commuting: photovoice and seeking well-being in everyday travel.
AB  - We used participant-produced photography to investigate everyday commuting
      practices in Cambridge, UK. Photovoice served as an observational method for
      producing ethnographically rich data. A total of 19 participants produced over
      500 photos about their journeys to and from work and took part in photo
      elicitation interviews. Three themes emerged. First, many images depicted 'well
      being' in commuting, for example, beautiful landscapes. Second, during
      elicitation interviews, participants described positive images that they intended
      but failed to capture in photos. Third, those participants who did not depict
      well-being described a lack of choice in their commuting, while those who
      acknowledged well-being seemed to do so in order to make practices of commuting
      meaningful and habitable. While our interpretations of photos of well-being could
      be subject to a methodological fallacy relating to a preference for positive over
      negative images in lay photography, we nonetheless suggest that the rich visual
      and oral narratives indicate a 'real' experience, albeit elicited through the
      photovoice.

PMID- 25972762
TI  - Review of lattice results concerning low-energy particle physics.
AB  - We review lattice results related to pion, kaon, [Formula: see text]- and
      [Formula: see text]-meson physics with the aim of making them easily accessible
      to the particle-physics community. More specifically, we report on the
      determination of the light-quark masses, the form factor [Formula: see text],
      arising in semileptonic [Formula: see text] transition at zero momentum transfer,
      as well as the decay-constant ratio [Formula: see text] of decay constants and
      its consequences for the CKM matrix elements [Formula: see text] and [Formula:
      see text]. Furthermore, we describe the results obtained on the lattice for some
      of the low-energy constants of [Formula: see text] and [Formula: see text] Chiral
      Perturbation Theory and review the determination of the [Formula: see text]
      parameter of neutral kaon mixing. The inclusion of heavy-quark quantities
      significantly expands the FLAG scope with respect to the previous review.
      Therefore, we focus here on [Formula: see text]- and [Formula: see text]-meson
      decay constants, form factors, and mixing parameters, since these are most
      relevant for the determination of CKM matrix elements and the global CKM
      unitarity-triangle fit. In addition we review the status of lattice
      determinations of the strong coupling constant [Formula: see text].

PMID- 25972764
TI  - Erratum: Increased fatty acid synthase expression in prostate biopsy cores
      predicts higher Gleason score in radical prostatectomy specimen.
AB  - [This corrects the article DOI: 10.1186/1472-6890-14-3.]. 

PMID- 25972765
TI  - Obesity prevention in early life: an opportunity to better support the role of
      Maternal and Child Health Nurses in Australia.
AB  - BACKGROUND: Because parents with young children access primary health care
      services frequently, a key opportunity arises for Maternal and Child Health (MCH)
      nurses to actively work with families to support healthy infant feeding practices
      and lifestyle behaviours. However, little is known regarding the extent to which
      MCH nurses promote obesity prevention practices and how such practices could be
      better supported. METHODS: This mixed methods study involved a survey of 56 MCH
      nurses (response rate 84.8 %), 16 of whom participated in semi-structured
      qualitative interviews. Both components aimed to examine the extent to which
      nurses addressed healthy infant feeding practices, healthy eating, active play
      and limiting sedentary behavior during routine consultations with young children
      0-5 years. Key factors influencing such practices and how they could be best
      supported were also investigated. All data were collected from September to
      December 2013. Survey data were analysed descriptively and triangulated with
      qualitative interview findings, the analysis of which was guided by grounded
      theory principles. RESULTS: Although nurses reported measuring height/length and
      weight in most consultations, almost one quarter (22.2 %) reported never/rarely
      using growth charts to identify infants or children at risk of overweight or
      obesity. This reflected a reluctance to raise the issue of weight with parents
      and a lack of confidence in how to address it. The majority of nurses reported
      providing advice on aspects of infant feeding relevant to obesity prevention at
      most consultations, with around a third (37 %) routinely provided advice on
      formula preparation. Less than half of nurses routinely promoted active play and
      only 30 % discussed limiting sedentary behaviour such as TV viewing. Concerns
      about parental receptiveness and maintaining rapport were key barriers to more
      effective implementation. CONCLUSION: While MCH nurses are well placed to address
      obesity prevention in early life, there is currently a missed public health
      opportunity. Improving nurse skills in behaviour change counseling will be key to
      increasing their confidence in raising sensitive lifestyle issues with parents to
      better integrate obesity prevention practices into normal MCH service delivery.

PMID- 25972766
TI  - The PPAR-gamma antagonist GW9662 elicits differentiation of M2c-like cells and
      upregulation of the MerTK/Gas6 axis: a key role for PPAR-gamma in human
      macrophage polarization.
AB  - BACKGROUND: The nuclear receptors PPAR-gamma and LXRs regulate macrophage lipid
      metabolism and macrophage mediated inflammation. We examined the influence of
      these molecules on macrophage alternative activation, with particular focus on
      differentiation of "M2c" anti-inflammatory cells. METHODS: We cultured human
      monocytes in M0, M1, M2a or M2c macrophage differentiating conditions, in the
      presence or absence of PPAR-gamma and LXR ligands. Flow cytometry was used to
      analyze membrane expression of phenotypic markers. Basal and LPS-stimulated
      production of soluble mediators was measured by ELISA. Efferocytosis assays were
      performed by coincubating monocytes/macrophages with apoptotic neutrophils.
      RESULTS: We found that PPAR-gamma inhibition, using the PPAR-gamma antagonist
      GW9662, elicits differentiation of M2c-like (CD206(+) CD163(+) CD16(+)) cells and
      upregulation of the MerTK/Gas6 axis. Exposure of differentiating macrophages to
      IFN-gamma, GM-CSF or LPS (M1 conditions), however, hampers GW9662 induction of
      MerTK and Gas6. When macrophages are differentiated with IL-4 (M2a conditions),
      addition of GW9662 results into an M2a (CD206(+) CD209(+) CD163(-) MerTK(-)) to
      M2c (CD206(high) CD209(-) CD163(+) MerTK(+)) polarization shift. Conversely, in
      the presence of dexamethasone (M2c conditions), the PPAR-gamma agonist
      rosiglitazone attenuates CD163 and MerTK upregulation. The LXR agonist T0901317
      induces MerTK independently of M2c polarization; indeed, CD206, CD163 and CD16
      are downregulated. GW9662-differentiated M2c-like cells secrete high levels of
      Gas6 and low amounts of TNF-alpha and IL-10, mimicking dexamethasone effects in
      vitro. However, unlike conventional M2c cells, GW9662-differentiated cells do not
      show enhanced efferocytic ability. CONCLUSIONS: Our results provide new insights
      into the role of PPAR-gamma and LXR receptors in human macrophage activation and
      reveal the existence of different patterns regulating MerTK expression.
      Unexpectedly, PPAR-gamma appears to negatively control the expansion of a
      discrete subset of M2c-like anti-inflammatory macrophages.

PMID- 25972767
TI  - Impact of precise modulation of reactive oxygen species levels on spermatozoa
      proteins in infertile men.
AB  - BACKGROUND: Elevated levels of reactive oxygen species (ROS) are detected in 25%
      to 80% of infertile men. They are involved in the pathology of male infertility.
      Understanding the effect of increasing levels of ROS on the differential
      expression of sperm proteins is important to understand the cellular processes
      and or/pathways that may be implicated in male infertility. The aim of this study
      was to examine differentially expressed proteins (DEPs) in spermatozoa from
      patients with low, medium and high ROS levels. METHODS: A total of 42 infertile
      men presenting for infertility and 17 proven fertile men were enrolled in the
      study. ROS levels were measured by chemiluminescence assay. Infertile men were
      divided into Low (0- < 93 RLU/s/10(6) sperm) (n = 11), Medium (>93-500
      RLU/s/10(6) sperm) (n = 17) and High ROS (>500 RLU/s/10(6) sperm) group (n = 14).
      All fertile men had ROS levels between 4-50 RLU/s/10(6) sperm. 4 subjects from
      fertile group and 4 each from the Low, Medium and High ROS were pooled. Protein
      extraction, protein estimation, gel separation of the proteins, in-gel digestion,
      LTQ-orbitrap elite hybrid mass spectrometry system was conducted. The DEPs, the
      cellular localization and pathways of DEPs involved were examined utilizing
      bioinformatics tools. RESULTS: 1035 proteins were identified in the 3 groups by
      global proteomic analysis. Of these, 305 were DEPs. 51 were unique to the Low ROS
      group, 47 Medium ROS group and 104 were unique to the High ROS group. 6 DEPs were
      identified by Uniprot and DAVID that had distinct reproductive functions and they
      were expressed only in 3 ROS groups but not in the control. CONCLUSIONS: We have
      for the first time demonstrated the presence of 6 DEPs with distinct reproductive
      functions only in men with low, medium or high ROS levels. These DEPs can serve
      as potential biomarkers of oxidative stress induced male infertility.

PMID- 25972760
TI  - QCD and strongly coupled gauge theories: challenges and perspectives.
AB  - We highlight the progress, current status, and open challenges of QCD-driven
      physics, in theory and in experiment. We discuss how the strong interaction is
      intimately connected to a broad sweep of physical problems, in settings ranging
      from astrophysics and cosmology to strongly coupled, complex systems in particle
      and condensed-matter physics, as well as to searches for physics beyond the
      Standard Model. We also discuss how success in describing the strong interaction
      impacts other fields, and, in turn, how such subjects can impact studies of the
      strong interaction. In the course of the work we offer a perspective on the many
      research streams which flow into and out of QCD, as well as a vision for future
      developments.

PMID- 25972768
TI  - Metabolic fate of fructose in human adipocytes: a targeted 13C tracer fate
      association study.
AB  - The development of obesity is becoming an international problem and the role of
      fructose is unclear. Studies using liver tissue and hepatocytes have contributed
      to the understanding of fructose metabolism. Excess fructose consumption also
      affects extra hepatic tissues including adipose tissue. The effects of fructose
      on human adipocytes are not yet fully characterized, although in vivo studies
      have noted increased adiposity and weight gain in response to fructose sweetened
      beverages. In order to understand and predict the metabolic responses of
      adipocytes to fructose, this study examined differentiating and differentiated
      human adipocytes in culture, exposed to a range of fructose concentrations
      equivalent to that reported in blood after consuming fructose. A stable isotope
      based dynamic profiling method using [U-13C6]-d-fructose tracer was used to
      examine the metabolism and fate of fructose. A targeted stable isotope tracer
      fate association method was used to analyze metabolic fluxes and flux surrogates
      with exposure to escalating fructose concentration. This study demonstrated that
      fructose stimulates anabolic processes in adipocytes robustly, including
      glutamate and de novo fatty acid synthesis. Furthermore, fructose also augments
      the release of free palmitate from fully differentiated adipocytes. These results
      imply that in the presence of fructose, the metabolic response of adipocytes in
      culture is altered in a dose dependent manner, particularly favoring increased
      glutamate and fatty acid synthesis and release, warranting further in vivo
      studies.

PMID- 25972770
TI  - Lipidomic analysis of plasma samples from women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder affecting between 5 and 18
      % of females of reproductive age and can be diagnosed based on a combination of
      clinical, ultrasound and biochemical features, none of which on its own is
      diagnostic. A lipidomic approach using liquid chromatography coupled with
      accurate mass high-resolution mass-spectrometry (LC-HRMS) was used to investigate
      if there were any differences in plasma lipidomic profiles in women with PCOS
      compared with control women at different stages of menstrual cycle. Plasma
      samples from 40 women with PCOS and 40 controls aged between 18 and 40 years were
      analysed in combination with multivariate statistical analyses. Multivariate data
      analysis (LASSO regression and OPLS-DA) of the sample lipidomics datasets showed
      a weak prediction model for PCOS versus control samples from the follicular and
      mid-cycle phases of the menstrual cycle, but a stronger model (specificity 85 %
      and sensitivity 95 %) for PCOS versus the luteal phase menstrual cycle controls.
      The PCOS vs luteal phase model showed increased levels of plasma triglycerides
      and sphingomyelins and decreased levels of lysophosphatidylcholines and
      phosphatidylethanolamines in PCOS women compared with controls. Lipid biomarkers
      of PCOS were tentatively identified which may be useful in distinguishing PCOS
      from controls especially when performed during the menstrual cycle luteal phase.

PMID- 25972769
TI  - Prediction of intracellular metabolic states from extracellular metabolomic data.
AB  - Metabolic models can provide a mechanistic framework to analyze information-rich
      omics data sets, and are increasingly being used to investigate metabolic
      alternations in human diseases. An expression of the altered metabolic pathway
      utilization is the selection of metabolites consumed and released by cells.
      However, methods for the inference of intracellular metabolic states from
      extracellular measurements in the context of metabolic models remain
      underdeveloped compared to methods for other omics data. Herein, we describe a
      workflow for such an integrative analysis emphasizing on extracellular
      metabolomics data. We demonstrate, using the lymphoblastic leukemia cell lines
      Molt-4 and CCRF-CEM, how our methods can reveal differences in cell metabolism.
      Our models explain metabolite uptake and secretion by predicting a more
      glycolytic phenotype for the CCRF-CEM model and a more oxidative phenotype for
      the Molt-4 model, which was supported by our experimental data. Gene expression
      analysis revealed altered expression of gene products at key regulatory steps in
      those central metabolic pathways, and literature query emphasized the role of
      these genes in cancer metabolism. Moreover, in silico gene knock-outs identified
      unique control points for each cell line model, e.g., phosphoglycerate
      dehydrogenase for the Molt-4 model. Thus, our workflow is well-suited to the
      characterization of cellular metabolic traits based on extracellular metabolomic
      data, and it allows the integration of multiple omics data sets into a cohesive
      picture based on a defined model context.

PMID- 25972771
TI  - Predicting retention time in hydrophilic interaction liquid chromatography mass
      spectrometry and its use for peak annotation in metabolomics.
AB  - Liquid chromatography coupled to mass spectrometry (LCMS) is widely used in
      metabolomics due to its sensitivity, reproducibility, speed and versatility.
      Metabolites are detected as peaks which are characterised by mass-over-charge
      ratio (m/z) and retention time (rt), and one of the most critical but also the
      most challenging tasks in metabolomics is to annotate the large number of peaks
      detected in biological samples. Accurate m/z measurements enable the prediction
      of molecular formulae which provide clues to the chemical identity of peaks, but
      often a number of metabolites have identical molecular formulae. Chromatographic
      behaviour, reflecting the physicochemical properties of metabolites, should also
      provide structural information. However, the variation in rt between analytical
      runs, and the complicating factors underlying the observed time shifts, make the
      use of such information for peak annotation a non-trivial task. To this end, we
      conducted Quantitative Structure-Retention Relationship (QSRR) modelling between
      the calculated molecular descriptors (MDs) and the experimental retention times
      (rts) of 93 authentic compounds analysed using hydrophilic interaction liquid
      chromatography (HILIC) coupled to high resolution MS. A predictive QSRR model
      based on Random Forests algorithm outperformed a Multiple Linear Regression based
      model, and achieved a high correlation between predicted rts and experimental rts
      (Pearson's correlation coefficient = 0.97), with mean and median absolute error
      of 0.52 min and 0.34 min (corresponding to 5.1 and 3.2 % error), respectively. We
      demonstrate that rt prediction with the precision achieved enables the systematic
      utilisation of rts for annotating unknown peaks detected in a metabolomics study.
      The application of the QSRR model with the strategy we outlined enhanced the peak
      annotation process by reducing the number of false positives resulting from
      database queries by matching accurate mass alone, and enriching the reference
      library. The predicted rts were validated using either authentic compounds or ion
      fragmentation patterns.

PMID- 25972772
TI  - GC-MS based targeted metabolic profiling identifies changes in the wheat
      metabolome following deoxynivalenol treatment.
AB  - Fusariumgraminearum and related species commonly infest grains causing the
      devastating plant disease Fusarium head blight (FHB) and the formation of
      trichothecene mycotoxins. The most relevant toxin is deoxynivalenol (DON), which
      acts as a virulence factor of the pathogen. FHB is difficult to control and
      resistance to this disease is a polygenic trait, mainly mediated by the
      quantitative trait loci (QTL) Fhb1 and Qfhs.ifa-5A. In this study we established
      a targeted GC-MS based metabolomics workflow comprising a standardized
      experimental setup for growth, treatment and sampling of wheat ears and
      subsequent GC-MS analysis followed by data processing and evaluation of QC
      measures using tailored statistical and bioinformatics tools. This workflow was
      applied to wheat samples of six genotypes with varying levels of Fusarium
      resistance, treated with either DON or water, and harvested 0, 12, 24, 48 and 96
      h after treatment. The results suggest that the primary carbohydrate metabolism
      and transport, the citric acid cycle and the primary nitrogen metabolism of wheat
      are clearly affected by DON treatment. Most importantly significantly elevated
      levels of amino acids and derived amines were observed. In particular, the
      concentrations of the three aromatic amino acids phenylalanine, tyrosine, and
      tryptophan increased. No clear QTL specific difference in the response could be
      observed except a generally faster increase in shikimate pathway intermediates in
      genotypes containing Fhb1. The overall workflow proved to be feasible and
      facilitated to obtain a more comprehensive picture on the effect of DON on the
      central metabolism of wheat.

PMID- 25972774
TI  - Single-use thermoplastic microfluidic burst valves enabling on-chip reagent
      storage.
AB  - A simple and reliable method for fabricating single-use normally closed burst
      valves in thermoplastic microfluidic devices is presented, using a process flow
      that is readily integrated into established workflows for the fabrication of
      thermoplastic microfluidics. An experimental study of valve performance reveals
      the relationships between valve geometry and burst pressure. The technology is
      demonstrated in a device employing multiple valves engineered to actuate at
      different inlet pressures that can be generated using integrated screw pumps. On
      chip storage and reconstitution of fluorescein salt sealed within defined reagent
      chambers are demonstrated. By taking advantage of the low gas and water
      permeability of cyclic olefin copolymer, the robust burst valves allow on-chip
      hermetic storage of reagents, making the technology well suited for the
      development of integrated and disposable assays for use at the point of care.

PMID- 25972773
TI  - MarVis-Pathway: integrative and exploratory pathway analysis of non-targeted
      metabolomics data.
AB  - A central aim in the evaluation of non-targeted metabolomics data is the
      detection of intensity patterns that differ between experimental conditions as
      well as the identification of the underlying metabolites and their association
      with metabolic pathways. In this context, the identification of metabolites based
      on non-targeted mass spectrometry data is a major bottleneck. In many
      applications, this identification needs to be guided by expert knowledge and
      interactive tools for exploratory data analysis can significantly support this
      process. Additionally, the integration of data from other omics platforms, such
      as DNA microarray-based transcriptomics, can provide valuable hints and thereby
      facilitate the identification of metabolites via the reconstruction of related
      metabolic pathways. We here introduce the MarVis-Pathway tool, which allows the
      user to identify metabolites by annotation of pathways from cross-omics data. The
      analysis is supported by an extensive framework for pathway enrichment and meta
      analysis. The tool allows the mapping of data set features by ID, name, and
      accurate mass, and can incorporate information from adduct and isotope correction
      of mass spectrometry data. MarVis-Pathway was integrated in the MarVis-Suite
      (http://marvis.gobics.de), which features the seamless highly interactive
      filtering, combination, clustering, and visualization of omics data sets. The
      functionality of the new software tool is illustrated using combined mass
      spectrometry and DNA microarray data. This application confirms jasmonate
      biosynthesis as important metabolic pathway that is upregulated during the wound
      response of Arabidopsis plants.

PMID- 25972775
TI  - Outbreaks of thrush in pigeons in Punjab State of India.
AB  - Due to high monetary turnover in business, white pigeon keeping for game purposes
      is gaining more popularity in Punjab. Overcrowding and poor management by
      undertrained naive farmers make these birds more susceptible to diseases not
      known so far in this region. A farmer reported that about a hundred pigeons were
      unable to feed properly and regurgitate feed. Birds lost body condition
      gradually, and three among these died. Both alive and dead pigeons were presented
      to the Veterinary Clinical Complex (VCC) for detailed examination. All these
      pigeons were found to be cachectic with wasting of breast muscles. On necropsy,
      no significant gross lesions were recorded in most of the visceral organs, except
      mottling of the liver. However, in the oral cavity, gray Turkish towel-like
      lesions were seen at the opening of the pharynx which continued into the larynx
      and proximal esophagus. Microscopic examination of material scrapped from lesions
      revealed a large number of budding yeast-like organisms and pseudohyphae,
      suggestive of Candida spp. Histologically, marked necrosis and sloughing of oral
      and esophageal mucosal epithelium with the presence of pyogranulomatous
      inflammation containing a large number of Candida organism were observed. To the
      authors' knowledge, there seems to be no outbreak of thrush in pigeons in Punjab
      previously.

PMID- 25972777
TI  - Toward a unified view of the speed-accuracy trade-off.

PMID- 25972776
TI  - Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome
      study.
AB  - The transcriptome of embryonic and adult rat lateral ventricular choroid plexus,
      using a combination of RNA-Sequencing and microarray data, was analyzed by
      functional groups of influx transporters, particularly solute carrier (SLC)
      transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with
      additional data obtained at intermediate ages from microarray analysis. The
      largest represented functional group in the embryo was amino acid transporters
      (twelve) with expression levels 2-98 times greater than in the adult. In
      contrast, in the adult only six amino acid transporters were up-regulated
      compared to the embryo and at more modest enrichment levels (<5-fold enrichment
      above E15). In E15 plexus five glucose transporters, in particular Glut-1, and
      only one monocarboxylate transporter were enriched compared to the adult, whereas
      only two glucose transporters but six monocarboxylate transporters in the adult
      plexus were expressed at higher levels than in embryos. These results are
      compared with earlier published physiological studies of amino acid and
      monocarboxylate transport in developing rodents. This comparison shows
      correlation of high expression of some transporters in the developing brain with
      higher amino acid transport activity reported previously. Data for divalent metal
      transporters are also considered. Immunohistochemistry of several transporters
      (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to
      confirm translational activity and to define cellular distribution of the
      proteins. Overall the results show that there is substantial expression of
      numerous influx transporters in the embryonic choroid plexus, many at higher
      levels than in the adult. This, together with immunohistochemical evidence and
      data from published physiological transport studies suggests that the choroid
      plexus in embryonic brain plays a major role in supplying the developing brain
      with essential nutrients. 

PMID- 25972778
TI  - A reconfigurable on-line learning spiking neuromorphic processor comprising 256
      neurons and 128K synapses.
AB  - Implementing compact, low-power artificial neural processing systems with real
      time on-line learning abilities is still an open challenge. In this paper we
      present a full-custom mixed-signal VLSI device with neuromorphic learning
      circuits that emulate the biophysics of real spiking neurons and dynamic synapses
      for exploring the properties of computational neuroscience models and for
      building brain-inspired computing systems. The proposed architecture allows the
      on-chip configuration of a wide range of network connectivities, including
      recurrent and deep networks, with short-term and long-term plasticity. The device
      comprises 128 K analog synapse and 256 neuron circuits with biologically
      plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it
      with on-line learning abilities. In addition to the analog circuits, the device
      comprises also asynchronous digital logic circuits for setting different synapse
      and neuron properties as well as different network configurations. This prototype
      device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4
      mm(2), and consumes approximately 4 mW for typical experiments, for example
      involving attractor networks. Here we describe the details of the overall
      architecture and of the individual circuits and present experimental results that
      showcase its potential. By supporting a wide range of cortical-like computational
      modules comprising plasticity mechanisms, this device will enable the realization
      of intelligent autonomous systems with on-line learning capabilities. 

PMID- 25972781
TI  - The effects of adolescent methamphetamine exposure.
AB  - Methamphetamine use among adolescents is a significant social and public health
      concern. Despite increased awareness of methamphetamine use among younger people,
      relatively little research has examined the effects of adolescent methamphetamine
      use compared to adult use. Thus, much remains to be learned about how
      methamphetamine alters adolescent brain function and behavior. In this article we
      review recent trends in adolescent methamphetamine use and data examining the
      effects of adolescent methamphetamine use on the dopaminergic system and behavior
      in humans and animal models. Future research is warranted to expand our
      understanding of the effects of adolescent methamphetamine exposure and how those
      effects differ from those seen in adults. 

PMID- 25972782
TI  - Consequences of temporary inhibition of the medial amygdala on social recognition
      memory performance in mice.
AB  - Different lines of investigation suggest that the medial amygdala is causally
      involved in the processing of information linked to social behavior in rodents.
      Here we investigated the consequences of temporary inhibition of the medial
      amygdala by bilateral injections of lidocaine on long-term social recognition
      memory as tested in the social discrimination task. Lidocaine or control NaCl
      solution was infused immediately before learning or before retrieval. Our data
      show that lidocaine infusion immediately before learning did not affect long-term
      memory retrieval. However, intra-amygdalar lidocaine infusions immediately before
      choice interfered with correct memory retrieval. Analysis of the aggressive
      behavior measured simultaneously during all sessions in the social recognition
      memory task support the impression that the lidocaine dosage used here was
      effective as it-at least partially-reduced the aggressive behavior shown by the
      experimental subjects toward the juveniles. Surprisingly, also infusions of NaCl
      solution blocked recognition memory at both injection time points. The results
      are interpreted in the context of the importance of the medial amygdala for the
      processing of non-volatile odors as a major contributor to the olfactory
      signature for social recognition memory. 

PMID- 25972783
TI  - Cellular glutathione content in the organ of Corti and its role during
      ototoxicity.
AB  - Glutathione (GSH) is the major scavenger of reactive oxygen species (ROS) inside
      cells. We used live confocal imaging in order to clarify the role of GSH in the
      biology of the organ of Corti, the sensory epithelium of the cochlea, before,
      during and after the onset of hearing and in ~1 year old mice. GSH content was
      measured using monochlorobimane (MCB), a non-fluorescent cell permeant bimane
      that reacts with GSH, forming a fluorescent adduct through a reaction catalyzed
      by glutathione-S-transferase. GSH content increased significantly in inner hair
      cells during maturation in young adult animals, whereas there was no significant
      change in the outer hair cells. However, the GSH content in inner hair cells was
      significantly reduced in ~1 year old mice. The GSH content of supporting cells
      was comparatively stable over these ages. To test whether the GSH content played
      a significant protective role during ototoxicity, GSH synthesis was inhibited by
      buthionine sulfoximine (BSO) in organotypic cochlear explant cultures from
      immature mice. BSO treatment alone, which reduced GSH by 65 and 85% in inner hair
      cells and outer hair cells respectively, did not cause any significant cell
      death. Surprisingly, GSH depletion had no significant effect on hair cell
      survival even during exposure to the ototoxic aminoglycoside neomycin. These data
      suggest that the involvement of ROS during aminoglycoside-induced hair cell death
      is less clear than previously thought and requires further investigation. 

PMID- 25972779
TI  - Rational modulation of the innate immune system for neuroprotection in ischemic
      stroke.
AB  - The innate immune system plays a dualistic role in the evolution of ischemic
      brain damage and has also been implicated in ischemic tolerance produced by
      different conditioning stimuli. Early after ischemia, perivascular astrocytes
      release cytokines and activate metalloproteases (MMPs) that contribute to blood
      brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages,
      they provide extracellular glutamate uptake, BBB regeneration and neurotrophic
      factors release. Similarly, early activation of microglia contributes to ischemic
      brain injury via the production of inflammatory cytokines, including tumor
      necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen
      species and proteases. Nevertheless, microglia also contributes to the resolution
      of inflammation, by releasing IL-10 and tumor growth factor (TGF)-beta, and to
      the late reparative processes by phagocytic activity and growth factors
      production. Indeed, after ischemia, microglia/macrophages differentiate toward
      several phenotypes: the M1 pro-inflammatory phenotype is classically activated
      via toll-like receptors or interferon-gamma, whereas M2 phenotypes are
      alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF
      beta. Thus, immune cells exert a dualistic role on the evolution of ischemic
      brain damage, since the classic phenotypes promote injury, whereas alternatively
      activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair.
      Moreover, a subdued activation of the immune system has been involved in ischemic
      tolerance, since different preconditioning stimuli act via modulation of
      inflammatory mediators, including toll-like receptors and cytokine signaling
      pathways. This further underscores that the immuno-modulatory approach for the
      treatment of ischemic stroke should be aimed at blocking the detrimental effects,
      while promoting the beneficial responses of the immune reaction. 

PMID- 25972780
TI  - ATP as a multi-target danger signal in the brain.
AB  - ATP is released in an activity-dependent manner from different cell types in the
      brain, fulfilling different roles as a neurotransmitter, neuromodulator, in
      astrocyte-to-neuron communication, propagating astrocytic responses and
      formatting microglia responses. This involves the activation of different ATP P2
      receptors (P2R) as well as adenosine receptors upon extracellular ATP catabolism
      by ecto-nucleotidases. Notably, brain noxious stimuli trigger a sustained
      increase of extracellular ATP, which plays a key role as danger signal in the
      brain. This involves a combined action of extracellular ATP in different cell
      types, namely increasing the susceptibility of neurons to damage, promoting
      astrogliosis and recruiting and formatting microglia to mount neuroinflammatory
      responses. Such actions involve the activation of different receptors, as
      heralded by neuroprotective effects resulting from blockade mainly of P2X7R,
      P2Y1R and adenosine A2A receptors (A2AR), which hierarchy, cooperation and/or
      redundancy is still not resolved. These pleiotropic functions of ATP as a danger
      signal in brain damage prompt a therapeutic interest to multi-target different
      purinergic receptors to provide maximal opportunities for neuroprotection. 

PMID- 25972784
TI  - Interplay of environmental signals and progenitor diversity on fate specification
      of cortical GABAergic neurons.
AB  - Cortical GABAergic interneurons constitute an extremely diverse population of
      cells organized in a well-defined topology of precisely interconnected cells.
      They play a crucial role regulating inhibitory-excitatory balance in brain
      circuits, gating sensory perception, and regulating spike timing to brain
      oscillations during distinct behaviors. Dysfunctions in the establishment of
      proper inhibitory circuits have been associated to several brain disorders such
      as autism, epilepsy, and schizophrenia. In the rodent adult cortex, inhibitory
      neurons are generated during the second gestational week from distinct progenitor
      lineages located in restricted domains of the ventral telencephalon. However,
      only recently, studies have revealed some of the mechanisms generating the
      heterogeneity of neuronal subtypes and their modes of integration in brain
      networks. Here we will discuss some the events involved in the production of
      cortical GABAergic neuron diversity with focus on the interaction between
      intrinsically driven genetic programs and environmental signals during
      development. 

PMID- 25972785
TI  - Highly differentiated cellular and circuit properties of infralimbic pyramidal
      neurons projecting to the periaqueductal gray and amygdala.
AB  - The infralimbic (IL) cortex is a key node in an inter-connected network involved
      in fear and emotion processing. The cellular and circuit-level mechanisms whereby
      IL neurons receive, filter, and modulate incoming signals they project onward to
      diverse downstream nodes in this complex network remain poorly understood. Using
      the mouse as our model, we applied anatomical labeling strategies, brain slice
      electrophysiology, and focal activation of caged glutamate via laser scanning
      photostimulation (glu-LSPS) for quantitative neurophysiological analysis of
      projectionally defined neurons in IL. Injection of retrograde tracers into the
      periaqueductal gray (PAG) and basolateral amygdala (BLA) was used to identify
      cortico-PAG (CP) and cortico-BLA (CA) neurons in IL. CP neurons were found
      exclusively in layer 5 (L5) of IL whereas CA neurons were detected throughout
      layer 2, 3, and 5 of IL. We also identified a small percentage of IL neurons that
      project to both the PAG and the BLA. We found that L5 CP neurons have a more
      extensive dendritic structure compared to L5 CA neurons. Neurophysiological
      recordings performed on retrogradely labeled neurons in acute brain slice showed
      that CP and CA neurons in IL could be broadly classified in two groups: neuronal
      resonators and non-resonators. Layer 2 CA neurons were the only class that was
      exclusively non-resonating. CP, CA, and CP/CA neurons in layers 3 and 5 of IL
      consisted of heterogeneous populations of resonators and non-resonators showing
      that projection target is not an exclusive predictor of intrinsic physiology.
      Circuit mapping using glu-LSPS revealed that the strength and organization of
      local excitatory and inhibitory inputs were stronger to CP compared to CA neurons
      in IL. Together, our results establish an organizational scheme linking cellular
      neurophysiology with microcircuit parameters of defined neuronal subclasses in IL
      that send descending commands to subcortical structures involved in fear
      behavior. 

PMID- 25972786
TI  - The dependence of neuronal encoding efficiency on Hebbian plasticity and
      homeostatic regulation of neurotransmitter release.
AB  - Synapses act as information filters by different molecular mechanisms including
      retrograde messenger that affect neuronal spiking activity. One of the well-known
      effects of retrograde messenger in presynaptic neurons is a change of the
      probability of neurotransmitter release. Hebbian learning describe a
      strengthening of a synapse between a presynaptic input onto a postsynaptic neuron
      when both pre- and postsynaptic neurons are coactive. In this work, a theory of
      homeostatic regulation of neurotransmitter release by retrograde messenger and
      Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was
      measured for different synaptic conditions. In order to gain high encoding
      efficiency, the spiking pattern of a neuron should be dependent on the intensity
      of the input and show low levels of noise. In this work, we represent spiking
      trains as zeros and ones (corresponding to non-spike or spike in a time bin,
      respectively) as words with length equal to three. Then the frequency of each
      word (here eight words) is measured using spiking trains. These frequencies are
      used to measure neuronal efficiency in different conditions and for different
      parameter values. Results show that neurons that have synapses acting as band
      pass filters show the highest efficiency to encode their input when both Hebbian
      mechanism and homeostatic regulation of neurotransmitter release exist in
      synapses. Specifically, the integration of homeostatic regulation of feedback
      inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter
      release in the synapses leads to even higher efficiency when high stimulus
      intensity is presented to the neurons. However, neurons with synapses acting as
      high-pass filters show no remarkable increase in encoding efficiency for all
      simulated synaptic plasticity mechanisms. This study demonstrates the importance
      of cooperation of Hebbian mechanism with regulation of neurotransmitter release
      induced by rapid diffused retrograde messenger in neurons with synapses as low
      and band-pass filters to obtain high encoding efficiency in different
      environmental and physiological conditions. 

PMID- 25972787
TI  - Spatial organization of excitatory synaptic inputs to layer 4 neurons in mouse
      primary auditory cortex.
AB  - Layer 4 (L4) of primary auditory cortex (A1) receives a tonotopically organized
      projection from the medial geniculate nucleus of the thalamus. However,
      individual neurons in A1 respond to a wider range of sound frequencies than would
      be predicted by their thalamic input, which suggests the existence of cross
      frequency intracortical networks. We used laser scanning photostimulation and
      uncaging of glutamate in brain slices of mouse A1 to characterize the spatial
      organization of intracortical inputs to L4 neurons. Slices were prepared to
      include the entire tonotopic extent of A1. We find that L4 neurons receive local
      vertically organized (columnar) excitation from layers 2 through 6 (L6) and
      horizontally organized excitation primarily from L4 and L6 neurons in regions
      centered ~300-500 MUm caudal and/or rostral to the cell. Excitatory horizontal
      synaptic connections from layers 2 and 3 were sparse. The origins of horizontal
      projections from L4 and L6 correspond to regions in the tonotopic map that are
      approximately an octave away from the target cell location. Such spatially
      organized lateral connections may contribute to the detection and processing of
      auditory objects with specific spectral structures. 

PMID- 25972789
TI  - Adaptation to elastic loads and BMI robot controls during rat locomotion examined
      with point-process GLMs.
AB  - Currently little is known about how a mechanically coupled BMI system's actions
      are integrated into ongoing body dynamics. We tested a locomotor task augmented
      with a BMI system driving a robot mechanically interacting with a rat under three
      conditions: control locomotion (BL), "simple elastic load" (E) and "BMI with
      elastic load" (BMI/E). The effect of the BMI was to allow compensation of the
      elastic load as a function of the neural drive. Neurons recorded here were close
      to one another in cortex, all within a 200 micron diameter horizontal distance of
      one another. The interactions of these close assemblies of neurons may differ
      from those among neurons at longer distances in BMI tasks and thus are important
      to explore. A point process generalized linear model (GLM), was used to examine
      connectivity at two different binning timescales (1 ms vs. 10 ms). We used GLM
      models to fit non-Poisson neural dynamics solely using other neurons' prior
      neural activity as covariates. Models at different timescales were compared based
      on Kolmogorov-Smirnov (KS) goodness-of-fit and parsimony. About 15% of cells with
      non-Poisson firing were well fitted with the neuron-to-neuron models alone. More
      such cells were fitted at the 1 ms binning than 10 ms. Positive connection
      parameters ("excitation" ~70%) exceeded negative parameters ("inhibition" ~30%).
      Significant connectivity changes in the GLM determined networks of well-fitted
      neurons occurred between the conditions. However, a common core of connections
      comprising at least ~15% of connections persisted between any two of the three
      conditions. Significantly almost twice as many connections were in common between
      the two load conditions (~27%), compared to between either load condition and the
      baseline. This local point process GLM identified neural correlation structure
      and the changes seen across task conditions in the rats in this neural subset may
      be intrinsic to cortex or due to feedback and input reorganization in adaptation.

PMID- 25972790
TI  - Enhanced brain susceptibility to negative stimuli in adolescents: ERP evidences.
AB  - BACKGROUND: Previous studies investigated neural substrates of emotional face
      processing in adolescents and its comparison with adults. As emotional faces
      elicit more of emotional expression recognition rather than direct emotional
      responding, it remains undetermined how adolescents are different from adults in
      brain susceptibility to emotionally stressful stimuli. METHODS: Event-Related
      Potentials (ERPs) were recorded for highly negative (HN), moderately negative
      (MN), and neutral pictures in 20 adolescents and 20 adults while subjects
      performed a standard/deviant distinction task by pressing different keys,
      irrespective of the emotionality of deviant stimuli. RESULTS: Adolescents
      exhibited more negative amplitudes for HN vs. neutral pictures in N1 (100-150
      ms), P2 (130-190 ms), N2 (210-290 ms), and P3 (360-440 ms) components. In
      addition, adolescents showed more negative amplitudes for MN compared to neutral
      pictures in N1, P2, and N2 components. By contrast, adults exhibited significant
      emotion effects for HN stimuli in N2 and P3 amplitudes but not in N1 and P2
      amplitudes, and they did not exhibit a significant emotion effect for MN stimuli
      at all these components. In the 210-290 ms time interval, the emotion effect for
      HN stimuli was significant across frontal and central regions in adolescents,
      while this emotion effect was noticeable only in the central region for adults.
      CONCLUSIONS: Adolescents are more emotionally sensitive to negative stimuli
      compared to adults, regardless of the emotional intensity of the stimuli,
      possibly due to the immature prefrontal control system over the limbic emotional
      inputs during adolescence.

PMID- 25972791
TI  - Motor cortical plasticity induced by motor learning through mental practice.
AB  - Several investigations suggest that actual and mental actions trigger similar
      neural substrates. Motor learning via physical practice results in long-term
      potentiation (LTP)-like plasticity processes, namely potentiation of M1 and a
      temporary occlusion of additional LTP-like plasticity. However, whether this
      neuroplasticity process contributes to improve motor performance through mental
      practice remains to be determined. Here, we tested skill learning-dependent
      changes in primary motor cortex (M1) excitability and plasticity by means of
      transcranial magnetic stimulation (TMS) in subjects trained to physically execute
      or mentally perform a sequence of finger opposition movements. Before and after
      physical practice and motor-imagery practice, M1 excitability was evaluated by
      measuring the input-output (IO) curve of motor evoked potentials. M1 LTP and long
      term depression (LTD)-like plasticity was assessed with paired-associative
      stimulation (PAS) of the median nerve and motor cortex using an interstimulus
      interval of 25 ms (PAS25) or 10 ms (PAS10), respectively. We found that even if
      after both practice sessions subjects significantly improved their movement
      speed, M1 excitability and plasticity were differentially influenced by the two
      practice sessions. First, we observed an increase in the slope of IO curve after
      physical but not after MI practice. Second, there was a reversal of the PAS25
      effect from LTP-like plasticity to LTD-like plasticity following physical and MI
      practice. Third, LTD-like plasticity (PAS10 protocol) increased after physical
      practice, whilst it was occluded after MI practice. In conclusion, we
      demonstrated that MI practice lead to the development of neuroplasticity, as it
      affected the PAS25- and PAS10- induced plasticity in M1. These results, expanding
      the current knowledge on how MI training shapes M1 plasticity, might have a
      potential impact in rehabilitation. 

PMID- 25972792
TI  - The male sex pheromone darcin stimulates hippocampal neurogenesis and cell
      proliferation in the subventricular zone in female mice.
AB  - The integration of newly generated neurons persists throughout life in the
      mammalian olfactory bulb and hippocampus, regions involved in olfactory and
      spatial learning. Social cues can be potent stimuli for increasing adult
      neurogenesis; for example, odors from dominant but not subordinate male mice
      increase neurogenesis in both brain regions of adult females. However, little is
      known about the role of neurogenesis in social recognition or the assessment of
      potential mates. Dominant male mice scent-mark territories using urine that
      contains a number of pheromones including darcin (MUP20), a male-specific major
      urinary protein that stimulates rapid learned attraction to the spatial location
      and individual odor signature of the scent owner. Here we investigate whether
      exposure to darcin stimulates neurogenesis in the female brain. Hippocampal
      neurons and cellular proliferation in the lateral ventricles that supply neurons
      to the olfactory bulbs increased in females exposed for 7 days to male urine
      containing at least 0.5 MUg/MUl darcin. Darcin was effective whether presented
      alone or in the context of male urine, but other information in male urine
      appeared to modulate the proliferative response. When exposed to urine from wild
      male mice, hippocampal proliferation increased only if urine was from the same
      individual over 7 days, suggesting that consistency of individual scent
      signatures is important. While 7 days exposure to male scent initiated the first
      stages of increased neurogenesis, this caused no immediate increase in female
      attraction to the scent or in the strength or robustness of spatial learning in
      short-term conditioned place preference tests. The reliable and consistent
      stimulation of neurogenesis by a pheromone important in rapid social learning
      suggests that this may provide an excellent model to explore the relationship
      between the integration of new neurons and plasticity in spatial and olfactory
      learning in a socially-relevant context. 

PMID- 25972793
TI  - Antisocial punishment in two social dilemmas.
AB  - The effect of sanctions on cooperation depends on social and cultural norms.
      While free riding is kept at bay by altruistic punishment in certain cultures,
      antisocial punishment carried out by free riders pushes back cooperation in
      others. In this paper we analyze sanctions in both a standard public goods game
      with a linear production function and an otherwise identical social dilemma in
      which the minimum contribution determines the group outcome. Experiments were run
      in a culture with traditionally high antisocial punishment (Southern Europe). We
      replicate the detrimental effect of antisocial sanctions on cooperation in the
      linear case. However, we find that punishment is still widely effective when
      actions are complementary: the provision of the public good significantly and
      substantially increases with sanctions, participants punish significantly less
      and sanctions radically transform conditional cooperation patterns to generate
      significant welfare gains. 

PMID- 25972788
TI  - Visual system plasticity in mammals: the story of monocular enucleation-induced
      vision loss.
AB  - The groundbreaking work of Hubel and Wiesel in the 1960's on ocular dominance
      plasticity instigated many studies of the visual system of mammals, enriching our
      understanding of how the development of its structure and function depends on
      high quality visual input through both eyes. These studies have mainly employed
      lid suturing, dark rearing and eye patching applied to different species to
      reduce or impair visual input, and have created extensive knowledge on binocular
      vision. However, not all aspects and types of plasticity in the visual cortex
      have been covered in full detail. In that regard, a more drastic deprivation
      method like enucleation, leading to complete vision loss appears useful as it has
      more widespread effects on the afferent visual pathway and even on non-visual
      brain regions. One-eyed vision due to monocular enucleation (ME) profoundly
      affects the contralateral retinorecipient subcortical and cortical structures
      thereby creating a powerful means to investigate cortical plasticity phenomena in
      which binocular competition has no vote.In this review, we will present current
      knowledge about the specific application of ME as an experimental tool to study
      visual and cross-modal brain plasticity and compare early postnatal stages up
      into adulthood. The structural and physiological consequences of this type of
      extensive sensory loss as documented and studied in several animal species and
      human patients will be discussed. We will summarize how ME studies have been
      instrumental to our current understanding of the differentiation of sensory
      systems and how the structure and function of cortical circuits in mammals are
      shaped in response to such an extensive alteration in experience. In conclusion,
      we will highlight future perspectives and the clinical relevance of adding ME to
      the list of more longstanding deprivation models in visual system research. 

PMID- 25972794
TI  - Noradrenergic activation of the basolateral amygdala enhances object recognition
      memory and induces chromatin remodeling in the insular cortex.
AB  - It is well established that arousal-induced memory enhancement requires
      noradrenergic activation of the basolateral complex of the amygdala (BLA) and
      modulatory influences on information storage processes in its many target
      regions. While this concept is well accepted, the molecular basis of such BLA
      effects on neural plasticity changes within other brain regions remains to be
      elucidated. The present study investigated whether noradrenergic activation of
      the BLA after object recognition training induces chromatin remodeling through
      histone post-translational modifications in the insular cortex (IC), a brain
      region that is importantly involved in object recognition memory. Male Sprague
      Dawley rats were trained on an object recognition task, followed immediately by
      bilateral microinfusions of norepinephrine (1.0 MUg) or saline administered into
      the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas
      norepinephrine treatment induced robust 24-h object recognition memory. Most
      importantly, this memory-enhancing dose of norepinephrine induced a global
      reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the
      IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at
      serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine
      administered into the BLA of non-trained control rats did not induce any changes
      in the histone marks investigated in this study. These findings indicate that
      noradrenergic activation of the BLA induces training-specific effects on
      chromatin remodeling mechanisms, and presumably gene transcription, in its target
      regions, which may contribute to the understanding of the molecular mechanisms of
      stress and emotional arousal effects on memory consolidation. 

PMID- 25972796
TI  - On and Off switches in the brain.

PMID- 25972795
TI  - Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice
      following postnatal exposure to chlorpyrifos: relation to expression of brain
      acetylcholinesterase mRNA.
AB  - Following reports of emotional psychopathology in children and adults exposed to
      organophosphates, the effects of postnatal chlorpyrifos (CPF) on fear
      conditioning and depression-like behaviors were tested in adult mice. Concomitant
      changes in expression of mRNA for synaptic and soluble splice variants of
      acetylcholinesterase (AChE) were examined in mouse pups and adults of the Balb/C
      and C57Bl/6 (B6) strains, which differ in their behavioral and hormonal stress
      response. Mice were injected subcutaneously with 1 mg/kg CPF on postnatal days 4
      10 and tested as adults for conditioned fear, sucrose preference, and forced
      swim. Acetylcholinesterase activity was assessed in the brains of pups on the
      first and last day of treatment. Expression of soluble and synaptic AChE mRNA was
      assessed in brains of treated pups and fear-conditioned adults using real-time
      PCR. Adult Balb/C mice exposed postnatally to CPF showed exacerbated fear
      conditioning and impaired active avoidance. Adult B6 mice exposed postnatally to
      CPF showed a more specific fear response to tones and less freezing in the inter
      tone intervals, in contrast to the vehicle-pretreated mice. Chlorpyrifos also
      attenuated sweet preference and enhanced climbing in the forced swim test.
      Chlorpyrifos-treated mice had increased expression of both synaptic and
      readthrough AChE transcripts in the hippocampus of Balb/C mice and decreased
      expression in the amygdala following fear-conditioning. In conclusion, postnatal
      CPF had long-term effects on fear and depression, as well as on expression of
      AChE mRNA. These changes may be related to alteration in the interaction between
      hippocampus and amygdala in regulating negative emotions. 

PMID- 25972797
TI  - The color red attracts attention in an emotional context. An ERP study.
AB  - The color red is known to influence psychological functioning, having both
      negative (e.g., blood, fire, danger), and positive (e.g., sex, food)
      connotations. The aim of our study was to assess the attentional capture by red
      colored images, and to explore the modulatory role of the emotional valence in
      this process, as postulated by Elliot and Maier (2012) color-in-context theory.
      Participants completed a dot-probe task with each cue comprising two images of
      equal valence and arousal, one containing a prominent red object and the other an
      object of different coloration. Reaction times were measured, as well as the
      event-related lateralizations of the EEG. Modulation of the lateralized
      components revealed that the color red captured and later held the attention in
      both positive and negative conditions, but not in a neutral condition. An overt
      motor response to the target stimulus was affected mainly by attention lingering
      over the visual field where the red cue had been flashed. However, a weak
      influence of the valence could still be detected in reaction times. Therefore,
      red seems to guide attention, specifically in emotionally-valenced circumstances,
      indicating that an emotional context can alter color's impact both on attention
      and motor behavior. 

PMID- 25972798
TI  - Evidence for morphological composition in compound words using MEG.
AB  - Psycholinguistic and electrophysiological studies of lexical processing show
      convergent evidence for morpheme-based lexical access for morphologically complex
      words that involves early decomposition into their constituent morphemes followed
      by some combinatorial operation. Considering that both semantically transparent
      (e.g., sailboat) and semantically opaque (e.g., bootleg) compounds undergo
      morphological decomposition during the earlier stages of lexical processing,
      subsequent combinatorial operations should account for the difference in the
      contribution of the constituent morphemes to the meaning of these different word
      types. In this study we use magnetoencephalography (MEG) to pinpoint the neural
      bases of this combinatorial stage in English compound word recognition. MEG data
      were acquired while participants performed a word naming task in which three word
      types, transparent compounds (e.g., roadside), opaque compounds (e.g.,
      butterfly), and morphologically simple words (e.g., brothel) were contrasted in a
      partial-repetition priming paradigm where the word of interest was primed by one
      of its constituent morphemes. Analysis of onset latency revealed shorter
      latencies to name compound words than simplex words when primed, further
      supporting a stage of morphological decomposition in lexical access. An analysis
      of the associated MEG activity uncovered a region of interest implicated in
      morphological composition, the Left Anterior Temporal Lobe (LATL). Only
      transparent compounds showed increased activity in this area from 250 to 470 ms.
      Previous studies using sentences and phrases have highlighted the role of LATL in
      performing computations for basic combinatorial operations. Results are in tune
      with decomposition models for morpheme accessibility early in processing and
      suggest that semantics play a role in combining the meanings of morphemes when
      their composition is transparent to the overall word meaning. 

PMID- 25972799
TI  - Combining universal beauty and cultural context in a unifying model of visual
      aesthetic experience.
AB  - In this work, I propose a model of visual aesthetic experience that combines
      formalist and contextual aspects of aesthetics. The model distinguishes between
      two modes of processing. First, perceptual processing is based on the intrinsic
      form of an artwork, which may or may not be beautiful. If it is beautiful, a
      beauty-responsive mechanism is activated in the brain. This bottom-up mechanism
      is universal amongst humans; it is widespread in the visual brain and responsive
      across visual modalities. Second, cognitive processing is based on contextual
      information, such as the depicted content, the intentions of the artist or the
      circumstances of the presentation of the artwork. Cognitive processing is
      partially top-down and varies between individuals according to their cultural
      experience. Processing in the two channels is parallel and largely independent.
      In the general case, an aesthetic experience is induced if processing in both
      channels is favorable, i.e., if there is resonance in the perceptual processing
      channel ("aesthetics of perception"), and successful mastering in the cognitive
      processing channel ("aesthetics of cognition"). I speculate that this
      combinatorial mechanism has evolved to mediate social bonding between members of
      a (cultural) group of people. Primary emotions can be elicited via both channels
      and modulate the degree of the aesthetic experience. Two special cases are
      discussed. First, in a subset of (post-)modern art, beauty no longer plays a
      prominent role. Second, in some forms of abstract art, beautiful form can be
      enjoyed with minimal cognitive processing. The model is applied to examples of
      Western art. Finally, implications of the model are discussed. In summary, the
      proposed model resolves the seeming contradiction between formalist perceptual
      approaches to aesthetic experience, which are based on the intrinsic beauty of
      artworks, and contextual approaches, which account for highly individual and
      culturally dependent aspects of aesthetics. 

PMID- 25972800
TI  - Extrastriate visual cortex reorganizes despite sequential bilateral occipital
      stroke: implications for vision recovery.
AB  - The extent of visual cortex reorganization following injury remains
      controversial. We report serial functional magnetic resonance imaging (fMRI) data
      from a patient with sequential posterior circulation strokes occurring 3 weeks
      apart, compared with data from an age-matched healthy control subject. At 8 days
      following a left occipital stroke, contralesional visual cortical activation was
      within expected striate and extrastriate sites, comparable to that seen in
      controls. Despite a further infarct in the right (previously unaffected
      hemisphere), there was evolution of visual cortical reorganization progressed. In
      this patient, there was evidence of utilization of peri-infarct sites (right
      sided) and recruitment of new activation sites in extrastriate cortices,
      including in the lateral middle and inferior temporal lobes. The changes over
      time corresponded topographically with the patient's lesion site and its
      connections. Reorganization of the surviving visual cortex was demonstrated 8
      days after the first stroke. Ongoing reorganization in extant cortex was
      demonstrated at the 6 month scan. We present a summary of mechanisms of recovery
      following stroke relevant to the visual system. We conclude that mature primary
      visual cortex displays considerable plasticity and capacity to reorganize,
      associated with evolution of visual field deficits. We discuss these findings and
      their implications for therapy within the context of current concepts in visual
      compensatory and restorative therapies. 

PMID- 25972801
TI  - Measuring treatment effects on dual-task performance: a framework for research
      and clinical practice.
AB  - The relevance of dual-task walking to everyday ambulation is widely acknowledged,
      and numerous studies have demonstrated that dual-task interference can
      significantly impact recovery of functional walking in people with neurological
      disorders. The magnitude and direction of dual-task interference is influenced by
      the interaction between the two tasks, including how individuals spontaneously
      prioritize their attention. Therefore, to accurately interpret and characterize
      dual-task interference and identify changes over time, it is imperative to
      evaluate single and dual-task performance in both tasks, as well as the tasks
      relative to each other. Yet, reciprocal dual-task effects (DTE) are frequently
      ignored. The purpose of this perspective paper is to present a framework for
      measuring treatment effects on dual-task interference, specifically taking into
      account the interactions between the two tasks and how this can provide
      information on whether overall dual-task capacity has improved or a different
      attentional strategy has been adopted. In discussing the clinical implications of
      using this framework, we provide specific examples of using this method and
      provide some explicit recommendations for research and clinical practice. 

PMID- 25972802
TI  - Continuous passive movement does not influence motor maps in healthy adults.
AB  - Hand weakness following stroke is often associated with a reduced representation
      of the hand in the primary motor cortex. Meaningful sensory input can induce
      sensorimotor reorganization in the brain, but the after-effect of continuous
      passive motion (CPM) on the cortical representation is unknown. The purpose of
      this study was to determine whether repeated sessions of continuous passive
      movement of the thumb induce a lasting increase in the motor cortical
      representation of a thumb muscle in healthy adults. Thirteen right-handed healthy
      adults (mean age 24.3 +/- 4.3 years) participated in the study. Single-pulse
      Transcranial Magnetic Stimulation (TMS) was delivered over the motor area of the
      target muscle (abductor pollicis brevis) before and/or after a thirty minute
      session of thumb CPM administered on three consecutive days. TMS was also
      delivered 5 days after cessation of the CPM intervention. The response to TMS
      (motor evoked potential) was recorded in the target muscle with surface EMG.
      Resting motor threshold (RMT), motor evoked potential amplitude at a specified
      intensity, and the area and volume of the cortical representation of the target
      muscle were measured. Thumb CPM had no significant effect on TMS parameters (p >
      0.05 all measures) and performance of an attention task remained unchanged within
      and across CPM sessions. The results suggest that three sessions of repetitive
      passive thumb movement is not sufficient to induce a change in the cortical
      representation of the thumb and is unlikely to reverse the decreased
      representation of the affected hand following stroke. 

PMID- 25972804
TI  - Changes in neural resting state activity in primary and higher-order motor areas
      induced by a short sensorimotor intervention based on the Feldenkrais method.
AB  - We use functional magnetic resonance imaging to investigate short-term neural
      effects of a brief sensorimotor intervention adapted from the Feldenkrais method,
      a movement-based learning method. Twenty-one participants (10 men, 19-30 years)
      took part in the study. Participants were in a supine position in the scanner
      with extended legs while an experienced Feldenkrais practitioner used a planar
      board to touch and apply minimal force to different parts of the sole and toes of
      their left foot under two experimental conditions. In the local condition, the
      practitioner explored movement within foot and ankle. In the global condition,
      the practitioner focused on the connection and support from the foot to the rest
      of the body. Before (baseline) and after each intervention (post-local, post
      global), we measured brain activity during intermittent pushing/releasing with
      the left leg and during resting state. Independent localizer tasks were used to
      identify regions of interest (ROI). Brain activity during left-foot pushing did
      not significantly differ between conditions in sensorimotor areas. Resting state
      activity (regional homogeneity, ReHo) increased from baseline to post-local in
      medial right motor cortex, and from baseline to post-global in the left
      supplementary/cingulate motor area. Contrasting post-global to post-local showed
      higher ReHo in right lateral motor cortex. ROI analyses showed significant
      increases in ReHo in pushing-related areas from baseline to both post-local and
      post-global, and this increase tended to be more pronounced post-local. The
      results of this exploratory study show that a short, non-intrusive sensorimotor
      intervention can have short-term effects on spontaneous cortical activity in
      functionally related brain regions. Increased resting state activity in higher
      order motor areas supports the hypothesis that the global intervention engages
      action-related neural processes. 

PMID- 25972803
TI  - Critical periods after stroke study: translating animal stroke recovery
      experiments into a clinical trial.
AB  - INTRODUCTION: Seven hundred ninety-five thousand Americans will have a stroke
      this year, and half will have a chronic hemiparesis. Substantial animal
      literature suggests that the mammalian brain has much potential to recover from
      acute injury using mechanisms of neuroplasticity, and that these mechanisms can
      be accessed using training paradigms and neurotransmitter manipulation. However,
      most of these findings have not been tested or confirmed in the rehabilitation
      setting, in large part because of the challenges in translating a conceptually
      straightforward laboratory experiment into a meaningful and rigorous clinical
      trial in humans. Through presentation of methods for a Phase II trial, we discuss
      these issues and describe our approach. METHODS: In rodents there is compelling
      evidence for timing effects in rehabilitation; motor training delivered at
      certain times after stroke may be more effective than the same training delivered
      earlier or later, suggesting that there is a critical or sensitive period for
      strongest rehabilitation training effects. If analogous critical/sensitive
      periods can be identified after human stroke, then existing clinical resources
      can be better utilized to promote recovery. The Critical Periods after Stroke
      Study (CPASS) is a phase II randomized, controlled trial designed to explore
      whether such a sensitive period exists. We will randomize 64 persons to receive
      an additional 20 h of upper extremity therapy either immediately upon rehab
      admission, 2-3 months after stroke onset, 6 months after onset, or to an
      observation-only control group. The primary outcome measure will be the Action
      Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points
      for later biomarker studies. CONCLUSION: CPASS is an example of the translation
      of rodent motor recovery experiments into the clinical setting; data obtained
      from this single site randomized controlled trial will be used to finalize the
      design of a Phase III trial.

PMID- 25972805
TI  - Inhibitory non-invasive brain stimulation to homologous language regions as an
      adjunct to speech and language therapy in post-stroke aphasia: a meta-analysis.
AB  - Chronic communication impairment is common after stroke, and conventional speech
      and language therapy (SLT) strategies have limited effectiveness in post-stroke
      aphasia. Neurorehabilitation with non-invasive brain stimulation techniques
      (NIBS)-particularly repetitive transcranial magnetic stimulation (rTMS) or
      transcranial direct current stimulation (tDCS)-may enhance the effects of SLT in
      selected patients. Applying inhibitory NIBS to specific homologous language
      regions may induce neural reorganization and reduce interhemispheric competition.
      This mini review highlights randomized controlled trials (RCTs) and randomized
      cross-over trials using low-frequency rTMS or cathodal tDCS over the non-lesioned
      non-language dominant hemisphere and performs an exploratory meta-analysis of
      those trials considered combinable. Using a random-effects model, a meta-analysis
      of nine eligible trials involving 215 participants showed a significant mean
      effect size of 0.51 (95% CI = 0.24-0.79) for the main outcome "accuracy of
      naming" in language assessment. No heterogeneity was observed (I (2) = 0%). More
      multicenter RCTs with larger populations and homogenous intervention protocols
      are required to confirm these and the longer-term effects. 

PMID- 25972806
TI  - Layers of human brain activity: a functional model based on the default mode
      network and slow oscillations.

PMID- 25972807
TI  - The CNP signal is able to silence a supra threshold neuronal model.
AB  - Several experimental results published in the literature showed that weak pulsed
      magnetic fields affected the response of the central nervous system. However, the
      specific biological mechanisms that regulate the observed behaviors are still
      unclear and further scientific investigation is required. In this work we
      performed simulations on a neuronal network model exposed to a specific pulsed
      magnetic field signal that seems to be very effective in modulating the brain
      activity: the Complex Neuroelectromagnetic Pulse (CNP). Results show that CNP can
      silence the neurons of a feed-forward network for signal intensities that depend
      on the strength of the bias current, the endogenous noise level and the specific
      waveforms of the pulses. Therefore, it is conceivable that a neuronal network
      model responds to the CNP signal with an inhibition of its activity. Further
      studies on more realistic neuronal networks are needed to clarify if such an
      inhibitory effect on neuronal tissue may be the basis of the induced analgesia
      seen in humans and the antinociceptive effects seen in animals when exposed to
      the CNP. 

PMID- 25972810
TI  - Will drug resistance against dolutegravir in initial therapy ever occur?
AB  - Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor
      (INSTI) and INSTIs are the latest class of potent anti-HIV drugs. Compared to the
      first generation INSTIs, raltegravir, and elvitegravir, DTG shows a limited cross
      resistance profile. More interestingly, clinical resistance mutations to DTG in
      treatment-naive patents have not been observed to this date. This review
      summarizes recent studies on resistance mutations to DTG and on our understanding
      of the mechanisms of resistance to DTG as well as future directions for research.

PMID- 25972809
TI  - Nicotinic modulation of glutamate receptor function at nerve terminal level: a
      fine-tuning of synaptic signals.
AB  - This review focuses on a specific interaction occurring between the nicotinic
      cholinergic receptors (nAChRs) and the glutamatergic receptors (GluRs) at the
      nerve endings level. We have employed synaptosomes in superfusion and
      supplemented and integrated our findings with data obtained using techniques from
      molecular biology and immuno-cytochemistry, and the assessment of receptor
      trafficking. In particular, we characterize the following: (1) the direct and
      unequivocal localization of native alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamatergic
      receptors on specific nerve terminals, (2) their pharmacological characterization
      and functional co-localization with nAChRs on the same nerve endings, and (3) the
      existence of synergistic or antagonistic interactions among them. Indeed, in the
      rat nucleus accumbens (NAc), the function of some AMPA and NMDA receptors present
      on the dopaminergic and glutamatergic nerve terminals can be regulated negatively
      or positively in response to a brief activation of nAChRs. This effect occurs
      rapidly and involves the trafficking of AMPA and NMDA receptors. The event takes
      place also at very low concentrations of nicotine and involves the activation of
      several nAChRs subtypes. This dynamic control by cholinergic nicotinic system of
      glutamatergic NMDA and AMPA receptors might therefore represent an important
      neuronal presynaptic adaptation associated with nicotine administration. The
      understanding of the role of these nicotine-induced functional changes might open
      new and interesting perspectives both in terms of explaining the mechanisms that
      underlie some of the effects of nicotine addiction and in the development of new
      drugs for smoking cessation. 

PMID- 25972808
TI  - Impact of age-related neuroglial cell responses on hippocampal deterioration.
AB  - Aging is one of the greatest risk factors for the development of sporadic age
      related neurodegenerative diseases and neuroinflammation is a common feature of
      this disease phenotype. In the immunoprivileged brain, neuroglial cells, which
      mediate neuroinflammatory responses, are influenced by the physiological factors
      in the microenvironment of the central nervous system (CNS). These physiological
      factors include but are not limited to cell-to-cell communication involving cell
      adhesion molecules, neuronal electrical activity and neurotransmitter and
      neuromodulator action. However, despite this dynamic control of neuroglial
      activity, in the healthy aged brain there is an alteration in the underlying
      neuroinflammatory response notably seen in the hippocampus, typified by
      astrocyte/microglia activation and increased pro-inflammatory cytokine production
      and signaling. These changes may occur without any overt concurrent pathology,
      however, they typically correlate with deteriorations in hippocamapal or
      cognitive function. In this review we examine two important phenomenons, firstly
      the relationship between age-related brain deterioration (focusing on hippocampal
      function) and underlying neuroglial response(s), and secondly how the latter
      affects molecular and cellular processes within the hippocampus that makes it
      vulnerable to age-related cognitive decline. 

PMID- 25972811
TI  - Pseudo-acetylation of K326 and K328 of actin disrupts Drosophila melanogaster
      indirect flight muscle structure and performance.
AB  - In striated muscle tropomyosin (Tm) extends along the length of F-actin
      containing thin filaments. Its location governs access of myosin binding sites on
      actin and, hence, force production. Intermolecular electrostatic associations are
      believed to mediate critical interactions between the proteins. For example,
      actin residues K326, K328, and R147 were predicted to establish contacts with
      E181 of Tm. Moreover, K328 also potentially forms direct interactions with E286
      of myosin when the motor is strongly bound. Recently, LC-MS/MS analysis of the
      cardiac acetyl-lysine proteome revealed K326 and K328 of actin were acetylated, a
      post-translational modification (PTM) that masks the residues' inherent positive
      charges. Here, we tested the hypothesis that by removing the vital actin charges
      at residues 326 and 328, the PTM would perturb Tm positioning and/or strong
      myosin binding as manifested by altered skeletal muscle function and structure in
      the Drosophila melanogaster model system. Transgenic flies were created that
      permit tissue-specific expression of K326Q, K328Q, or K326Q/K328Q acetyl-mimetic
      actin and of wild-type actin via the UAS-GAL4 bipartite expression system.
      Compared to wild-type actin, muscle-restricted expression of mutant actin had a
      dose-dependent effect on flight ability. Moreover, excessive K328Q and
      K326Q/K328Q actin overexpression induced indirect flight muscle degeneration, a
      phenotype consistent with hypercontraction observed in other Drosophila
      myofibrillar mutants. Based on F-actin-Tm and F-actin-Tm-myosin models and on our
      physiological data, we conclude that acetylating K326 and K328 of actin alters
      electrostatic associations with Tm and/or myosin and thereby augments contractile
      properties. Our findings highlight the utility of Drosophila as a model that
      permits efficient targeted design and assessment of molecular and tissue-specific
      responses to muscle protein modifications, in vivo. 

PMID- 25972813
TI  - Editorial: Mechanotransduction and development of cardiovascular form and
      function.

PMID- 25972812
TI  - Treatment of chronic kidney diseases with histone deacetylase inhibitors.
AB  - Histone deacetylases (HDACs) induce deacetylation of both histone and non-histone
      proteins and play a critical role in the modulation of physiological and
      pathological gene expression. Pharmacological inhibition of HDAC has been
      reported to attenuate progression of renal fibrogenesis in obstructed kidney and
      reduce cyst formation in polycystic kidney disease. HDAC inhibitors (HDACis) are
      also able to ameliorate renal lesions in diabetes nephropathy, lupus nephritis,
      aristolochic acid nephropathy, and transplant nephropathy. The beneficial effects
      of HDACis are associated with their anti-fibrosis, anti-inflammation, and
      immunosuppressant effects. In this review, we summarize recent advances on the
      treatment of various chronic kidney diseases with HDACis in pre-clinical models. 

PMID- 25972814
TI  - HIPK2 is a new drug target for anti-fibrosis therapy in kidney disease.
AB  - In vitro and animal studies continue to elucidate the mechanisms of fibrosis and
      have led to advancements in treatment for idiopathic pulmonary fibrosis and
      cirrhosis, but the search for treatments for renal fibrosis has been more
      disappointing. Here, we will discuss homeodomain-interacting-protein kinase 2
      (HIPK2), a novel regulator of fibrosis that acts upstream of major fibrosis
      signaling pathways. Its key role in renal fibrosis has been validated in vitro
      and in several murine models of chronic kidney diseases (CKD). 

PMID- 25972815
TI  - Proteomic analysis of media from lung cancer cells reveals role of 14-3-3
      proteins in cachexia.
AB  - AIMS: At the time of diagnosis, 60% of lung cancer patients present with
      cachexia, a severe wasting syndrome that increases morbidity and mortality.
      Tumors secrete multiple factors that contribute to cachectic muscle wasting, and
      not all of these factors have been identified. We used Orbitrap electrospray
      ionization mass spectrometry to identify novel cachexia-inducing candidates in
      media conditioned with Lewis lung carcinoma cells (LCM). RESULTS: One-hundred and
      58 proteins were confirmed in three biological replicates. Thirty-three were
      identified as secreted proteins, including 14-3-3 proteins, which are highly
      conserved adaptor proteins known to have over 200 binding partners. We confirmed
      the presence of extracellular 14-3-3 proteins in LCM via western blot and
      discovered that LCM contained less 14-3-3 content than media conditioned with
      C2C12 myotubes. Using a neutralizing antibody, we depleted extracellular 14-3-3
      proteins in myotube culture medium, which resulted in diminished myosin content.
      We identified the proposed receptor for 14-3-3 proteins, CD13, in differentiated
      C2C12 myotubes and found that inhibiting CD13 via Bestatin also resulted in
      diminished myosin content. CONCLUSIONS: Our novel findings show that
      extracellular 14-3-3 proteins may act as previously unidentified myokines and may
      signal via CD13 to help maintain muscle mass.

PMID- 25972816
TI  - A critical assessment of the equal-environment assumption of the twin method for
      schizophrenia.
AB  - The classical twin method (CTM) is central to the view that schizophrenia is ~80%
      heritable. The CTM rests on the equal-environment assumption (EEA) that identical
      and fraternal twin pairs experience equivalent trait-relevant environmental
      exposures. The EEA has not been directly tested for schizophrenia with measures
      of child social adversity, which is particularly etiologically relevant to the
      disorder. However, if child social adversity is more similar in identical than
      fraternal pairs in the general twin population, the EEA is unlikely to be valid
      for schizophrenia, a question which we tested in this study. Using results from
      prior twin studies, we tested if intraclass correlations for the following five
      categories of child social adversity are larger in identical than fraternal
      twins: bullying, sexual abuse, physical maltreatment, emotional neglect and
      abuse, and general trauma. Eleven relevant studies that encompassed 9119 twin
      pairs provided 24 comparisons of intraclass correlations, which we grouped into
      the five social exposure categories. Fisher's z-test revealed significantly
      higher correlations in identical than fraternal pairs for each exposure category
      (z >= 3.53, p < 0.001). The difference remained consistent across gender, study
      site (country), sample size, whether psychometric instruments were used, whether
      interviewing was proximate or distant to the exposures, and whether informants
      were twins or third persons. Combined with other evidence that the differential
      intraclass correlation for child social adversity cannot be explained by
      evocative gene-environment covariation, our results indicate that the CTM does
      not provide any valid indication of genomic effects in schizophrenia. 

PMID- 25972818
TI  - Ambiguity tolerance in organizations: definitional clarification and perspectives
      on future research.
AB  - Ambiguity tolerance is an increasingly popular subject for study in a wide
      variety of fields. The definition of ambiguity tolerance has changed since its
      inception, and accompanying that change are changes in measurement and the
      research questions that interest researchers. There is a wealth of opportunity
      for research related to ambiguity tolerance and recent advances in neuroscience,
      measurement, trait research, perception, problem solving, and other fields
      highlight areas of interest and point to issues that need further attention. The
      future of ambiguity tolerance research is promising and it is expected that
      future studies will yield new insights into individual differences in reactions
      to the complex, unfamiliar, confusing, indeterminate, and incomplete stimuli that
      fall within the conceptual domain of ambiguity. 

PMID- 25972817
TI  - Reducing Delusional Conviction through a Cognitive-Based Group Training Game: A
      Multicentre Randomized Controlled Trial.
AB  - OBJECTIVE: "Michael's game" (MG) is a card game targeting the ability to generate
      alternative hypotheses to explain a given experience. The main objective was to
      evaluate the effect of MG on delusional conviction as measured by the primary
      study outcome: the change in scores on the conviction subscale of the Peters
      delusions inventory (PDI-21). Other variables of interest were the change in
      scores on the distress and preoccupation subscales of the PDI-21, the brief
      psychiatric rating scale, the Beck cognitive insight scale, and belief
      flexibility assessed with the Maudsley assessment of delusions schedule (MADS).
      METHODS: We performed a parallel, assessor-blinded, randomized controlled
      superiority trial comparing treatment as usual plus participation in MG with
      treatment as usual plus being on a waiting list (TAU) in a sample of adult
      outpatients with psychotic disorders and persistent positive psychotic symptoms
      at inclusion. RESULTS: The 172 participants were randomized, with 86 included in
      each study arm. Assessments were performed at inclusion (T1: baseline), at 3
      months (T2: post-treatment), and at 6 months after the second assessment (T3:
      follow-up). At T2, a positive treatment effect was observed on the primary
      outcome, the PDI-21 conviction subscale (p = 0.005). At T3, a sustained effect
      was observed for the conviction subscale (p = 0.002). Further effects were also
      observed at T3 on the PDI-21 distress (p = 0.002) and preoccupation subscales (p
      = 0.001), as well as on one of the MADS measures of belief flexibility ("anything
      against the belief") (p = 0.001). CONCLUSION: The study demonstrated some
      significant beneficial effect of MG.

PMID- 25972819
TI  - Audiovisual integration of speech in a patient with Broca's Aphasia.
AB  - Lesions to Broca's area cause aphasia characterized by a severe impairment of the
      ability to speak, with comparatively intact speech perception. However, some
      studies have found effects on speech perception under adverse listening
      conditions, indicating that Broca's area is also involved in speech perception.
      While these studies have focused on auditory speech perception other studies have
      shown that Broca's area is activated by visual speech perception. Furthermore,
      one preliminary report found that a patient with Broca's aphasia did not
      experience the McGurk illusion suggesting that an intact Broca's area is
      necessary for audiovisual integration of speech. Here we describe a patient with
      Broca's aphasia who experienced the McGurk illusion. This indicates that an
      intact Broca's area is not necessary for audiovisual integration of speech. The
      McGurk illusions this patient experienced were atypical, which could be due to
      Broca's area having a more subtle role in audiovisual integration of speech. The
      McGurk illusions of a control subject with Wernicke's aphasia were, however, also
      atypical. This indicates that the atypical McGurk illusions were due to deficits
      in speech processing that are not specific to Broca's aphasia. 

PMID- 25972821
TI  - The development of ingroup favoritism in repeated social dilemmas.
AB  - In two comprehensive and fully incentivized studies, we investigate the
      development of ingroup favoritism as one of two aspects of parochial altruism in
      repeated social dilemmas. Specifically, we test whether ingroup favoritism is a
      fixed phenomenon that can be observed from the very beginning and remains stable
      over time, or whether it develops (increases vs. decreases) during repeated
      contact. Ingroup favoritism is assessed through cooperation behavior in a
      repeated continuous prisoner's dilemma where participants sequentially interact
      with 10 members of the ingroup (own city and university) and subsequently with 10
      members of the outgroup (other city and university), or vice versa. In none of
      the experiments do we observe initial differences in cooperation behavior for
      interaction partners from the ingroup, as compared to outgroup, and we only
      observe small differences in expectations regarding the interaction partners'
      cooperation behavior. After repeated interaction, however, including a change of
      groups, clear ingroup favoritism can be observed. Instead of being due to gradual
      and potentially biased updating of expectations, we found that these emerging
      differences were mainly driven by the change of interaction partners' group
      membership that occurred after round 10. This indicates that in social dilemma
      settings ingroup favoritism is to some degree dynamic in that it is enhanced and
      sometimes only observable if group membership is activated by thinking about both
      the interaction with the ingroup and the outgroup. 

PMID- 25972823
TI  - Evidence consistent with the multiple-bearings hypothesis from human virtual
      landmark-based navigation.
AB  - One approach to explaining the conditions under which additional landmarks will
      be learned or ignored relates to the nature of the information provided by the
      landmarks (i.e., distance versus bearings). In the current experiment, we tested
      the ability of such an approach to explain the search behavior of human
      participants in a virtual landmark-based navigation task by manipulating whether
      landmarks provided stable distance, stable direction, or both stable distance and
      stable direction information. First, we incrementally shaped human participants'
      search behavior in the presence of two ambiguous landmarks. Next, participants
      experienced one additional landmark that disambiguated the location of the goal.
      Finally, we presented three additional landmarks. In a control condition, the
      additional landmarks maintained stable distances and bearings to the goal across
      trials. In a stable bearings condition, the additional landmarks varied in their
      distances but maintained fixed bearings to the goal across trials. In a stable
      distance condition, the additional landmarks varied in their bearings but
      maintained fixed distances to the goal across trials. Landmark stability, in
      particular, the stability of landmark-to-goal bearings, affected learning of the
      added landmarks. We interpret the results in the context of the theories of
      spatial learning that incorporate the nature of the information provided by
      landmarks. 

PMID- 25972822
TI  - The developmental onset of symbolic approximation: beyond nonsymbolic
      representations, the language of numbers matters.
AB  - Symbolic (i.e., with Arabic numerals) approximate arithmetic with large
      numerosities is an important predictor of mathematics. It was previously
      evidenced to onset before formal schooling at the kindergarten age (Gilmore et
      al., 2007) and was assumed to map onto pre-existing nonsymbolic (i.e., abstract
      magnitudes) representations. With a longitudinal study (Experiment 1), we show,
      for the first time, that nonsymbolic and symbolic arithmetic demonstrate
      different developmental trajectories. In contrast to Gilmore et al.'s (2007)
      findings, Experiment 1 showed that symbolic arithmetic onsets in grade 1, with
      the start of formal schooling, not earlier. Gilmore et al. (2007) had examined
      English-speaking children, whereas we assessed a large Dutch-speaking sample. The
      Dutch language for numbers can be cognitively more demanding, for example, due to
      the inversion property in numbers above 20. Thus, for instance, the number 48 is
      named in Dutch "achtenveertig" (eight and forty) instead of "forty eight." To
      examine the effect of the language of numbers, we conducted a cross-cultural
      study with English- and Dutch-speaking children that had similar SES and math
      achievement skills (Experiment 2). Results demonstrated that Dutch-speaking
      kindergarteners lagged behind English-speaking children in symbolic arithmetic,
      not nonsymbolic and demonstrated a working memory overload in symbolic
      arithmetic, not nonsymbolic. Also, we show for the first time that the ability to
      name two-digit numbers highly correlates with symbolic approximate arithmetic not
      nonsymbolic. Our experiments empirically demonstrate that the symbolic number
      system is modulated more by development and education than the nonsymbolic
      system. Also, in contrast to the nonsymbolic system, the symbolic system is
      modulated by language. 

PMID- 25972824
TI  - Higher in status, (Even) better-than-average.
AB  - In 5 studies (total N = 1357) conducted online using Amazon's MTurk the
      relationship between socioeconomic status (SES) and the better-than-average
      effect (BTAE) was tested. Across the studies subjective measures of SES were
      positively correlated with magnitude of BTAE. Effects of objective measures
      (income and education) were weaker and less consistent. Measures of childhood SES
      (both objective and subjective) were positively correlated with BTAE magnitude,
      though less strongly and less consistently than measures of current subjective
      SES. Meta-analysis revealed all measures of chronic SES (with the exception of
      education) were significantly correlated with BTAE. However, manipulations of SES
      in terms of subjective status (Study 2), power (Study 3), and dominance (Study 4)
      did not have strong effects on BTAE magnitude (d's ranging from -0.04 to -0.14).
      Taken together the results suggest that chronic, but not temporary, status may be
      linked with a stronger tendency to overestimate one's abilities and positive
      traits. 

PMID- 25972820
TI  - Musical training as an alternative and effective method for neuro-education and
      neuro-rehabilitation.
AB  - In the last decade, important advances in the field of cognitive science,
      psychology, and neuroscience have largely contributed to improve our knowledge on
      brain functioning. More recently, a line of research has been developed that aims
      at using musical training and practice as alternative tools for boosting specific
      perceptual, motor, cognitive, and emotional skills both in healthy population and
      in neurologic patients. These findings are of great hope for a better treatment
      of language-based learning disorders or motor impairment in chronic non
      communicative diseases. In the first part of this review, we highlight several
      studies showing that learning to play a musical instrument can induce substantial
      neuroplastic changes in cortical and subcortical regions of motor, auditory and
      speech processing networks in healthy population. In a second part, we provide an
      overview of the evidence showing that musical training can be an alternative, low
      cost and effective method for the treatment of language-based learning impaired
      populations. We then report results of the few studies showing that training with
      musical instruments can have positive effects on motor, emotional, and cognitive
      deficits observed in patients with non-communicable diseases such as stroke or
      Parkinson Disease. Despite inherent differences between musical training in
      educational and rehabilitation contexts, these results favor the idea that the
      structural, multimodal, and emotional properties of musical training can play an
      important role in developing new, creative and cost-effective intervention
      programs for education and rehabilitation in the next future. 

PMID- 25972825
TI  - Transcutaneous Vagus Nerve Stimulation (tVNS) does not increase prosocial
      behavior in Cyberball.
AB  - Emerging research suggests that individuals experience vicarious social pain
      (i.e., ostracism). It has been proposed that observing ostracism increases
      activity in the insula and in the prefrontal cortex (PFC), two key brain regions
      activated by directly experiencing ostracism. Here, we assessed the causal role
      of the insula and PFC in modulating neural activity in these areas by applying
      transcutaneous Vagus Nerve Stimulation (tVNS), a new non-invasive and safe method
      to stimulate the vagus nerve that has been shown to activate the insula and PFC.
      A single-blind, sham-controlled, within-subjects design was used to assess the
      effect of on-line (i.e., stimulation overlapping with the critical task) tVNS in
      healthy young volunteers (n = 24) on the prosocial Cyberball game, a virtual ball
      tossing game designed to measure prosocial compensation of ostracism. Active tVNS
      did not increase prosocial helping behavior toward an ostracized person, as
      compared to sham (placebo) stimulation. Corroborated by Bayesian inference, we
      conclude that tVNS does not modulate reactions to vicarious ostracism, as indexed
      by performance in a Cyberball game. 

PMID- 25972826
TI  - Early substance consumption and problematic use of video games in adolescence.
AB  - Substance use as well as use of video games is frequent among young people. The
      purpose of this research was to study the links between the use of video games
      and the consumption of various substances such as alcohol, tobacco or cannabis at
      adolescence. In order to do so, 1423 students from middle and high schools filled
      an auto-questionnaire that included questions on age, gender, year of study, use
      of video games and consumptions of alcohol (Alcohol Use Disorders Identification
      Test Short version, AUDIT-C), tobacco (Heaviness of Smoking Index, HSI), and
      cannabis (Cannabis Abuse Screening Test, CAST). We found that 92.1% of teens use
      video games and 17.7% have a problematic use of video games (PUVG). Furthermore,
      results show that substance consumption seems frequent with 19.8 and 8.3% of
      participants having hazardous alcohol and cannabis consumptions respectively and
      5.2% having a moderate to high tobacco dependence. Video gamers consumed
      significantly more alcohol and gamers with PUVG started their substance
      consumption (alcohol, tobacco, and cannabis) earlier. PUVG was found to be
      negatively correlated to age at first substance consumption, but positively
      correlated to the time spent playing video games. However, it was not correlated
      to risks of substance dependence (scores of AUDIT-C, HSI, and CAST). Finally, our
      results are consistent with the literature, in regard to frequency of substance
      use and use of video games in adolescence. These data will allow for a better
      consideration of prevention strategies and future care in this particular field. 

PMID- 25972828
TI  - Child-caregiver interaction in two remote Indigenous Australian communities.
AB  - This paper reports on a study in two remote multilingual Indigenous Australian
      communities: Yakanarra in the Kimberley region of Western Australia and Tennant
      Creek in the Barkly region of the Northern Territory. In both communities,
      processes of language shift are underway from a traditional language (Walmajarri
      and Warumungu, respectively) to a local creole variety (Fitzroy Valley Kriol and
      Wumpurrarni English, respectively). The study focuses on language input from
      primary caregivers to a group of preschool children, and on the children's
      productive language. The study further highlights child-caregiver interactions as
      a site of importance in understanding the broader processes of language shift. We
      use longitudinal data from two time-points, approximately 2 years apart, to
      explore changes in adult input over time and developmental patterns in the
      children's speech. At both time points, the local creole varieties are the
      preferred codes of communication for the dyads in this study, although there is
      some use of the traditional language in both communities. Results show that for
      measures of turn length (MLT), there are notable differences between the two
      communities for both the focus children and their caregivers. In Tennant Creek,
      children and caregivers use longer turns at Time 2, while in Yakanarra the
      picture is more variable. The two communities also show differing trends in terms
      of conversational load (MLT ratio). For measures of morphosyntactic complexity
      (MLU), children and caregivers in Tennant Creek use more complex utterances at
      Time 2, while caregivers in Yakanarra show less complexity in their language at
      that time point. The study's findings contribute to providing a more detailed
      picture of the multilingual practices at Yakanarra and Tennant Creek, with
      implications for understanding broader processes of language shift. They also
      elucidate how children's language and linguistic input varies diachronically
      across time. As such, we contribute to understandings of normative language
      development for non-Western, non middle-class children in multilingual contexts. 

PMID- 25972827
TI  - Interaction of physical activity and interoception in children.
AB  - BACKGROUND: Physical activity (PA) is associated with positive health outcomes,
      whereas physical inactivity is related to an increased risk for various health
      issues including obesity and cardiovascular diseases. Previous research indicates
      that interindividual differences in the perception of bodily processes
      (interoceptive sensitivity, IS) interact with the degree of PA in adults. Whether
      there is a similar relationship between PA and IS in children has not been
      investigated yet. Therefore, the aim of this study was to investigate the
      interaction between IS and PA during physical performance tasks and in everyday
      situations. METHODS: IS was assessed using a heartbeat perception task in a
      sample of 49 children within the health promotion program "Join the Healthy Boat"
      which is implemented in several primary schools in the southwest of Germany. PA
      was examined using a physical performance task, assessing the distance covered
      during a standardized 6-min run. In a subsample of 21 children, everyday PA was
      measured by a multi-sensor device (Actiheart, CamNtech, Cambridge, UK) during
      five consecutive days with more than 10 h of daily data collection. RESULTS:
      Children with higher IS performed better in the physical performance task.
      Additionally, based on energy expenditure defined as metabolic equivalents, IS
      was positively correlated with the extent of light PA levels in the morning and
      afternoon. CONCLUSION: Our findings reveal that IS interacts positively with the
      degree of PA in children supporting the idea that interoception is important for
      the self-regulation of health-related behavior.

PMID- 25972829
TI  - Recruitment strategies should not be randomly selected: empirically improving
      recruitment success and diversity in developmental psychology research.
AB  - Psychological and developmental research have been critiqued for the lack of
      diversity of research samples. Because differences in culture, race, and
      ethnicity can influence participant behavior, limited diversity limits the
      generalizability of the findings. These differences may also impact how
      participants behave in response to recruitment attempts, which suggests that
      recruitment itself may be leveraged to increase sample diversity. The goal of the
      current study was to determine what factors, within a recruitment interaction,
      could be leveraged to increase success and diversity when recruiting families
      with children for developmental research. Study 1 found three factors influenced
      success: (1) recruitment was more successful when other potential participants
      were also interested (i.e., recruiters were busy), (2) recruiters of particular
      races were more successful than recruiters of other races, and (3) differences in
      success were related to what the recruiter said to engage the potential
      participant (i.e., the script). The latter two factors interacted, suggesting
      some recruiters were using less optimal scripts. To improve success rates, study
      2 randomly assigned scripts to recruiters and encouraged them to recruit more
      vigorously during busy periods. Study 2 found that two factors influenced
      success: (1) some scripts were more successful than others and (2) we were more
      successful at recruiting non-White potential participants than White
      participants. These two interacted, with some scripts being more successful with
      White and other scripts being more successful with non-White families. This
      intervention significantly increased recruitment success rate by 8.1% and the
      overall number of families recruited by 15.3%. These findings reveal that
      empirically evaluating and tailoring recruitment efforts based on the most
      successful strategies is effective in boosting diversity through increased
      participation of children from non-White families. 

PMID- 25972830
TI  - Origin of music and embodied cognition.

PMID- 25972831
TI  - Extending decision making competence to special populations: a pilot study of
      persons on the autism spectrum.
AB  - The area of decision making has much to offer in our effort to understand special
      populations. This pilot study is an example of just such a project, where we
      illustrate how traditional decision making tools and tasks can be used to uncover
      strengths and weaknesses within a growing population of young adults with autism.
      In this pilot project we extended accounts of autistic behavior such as those
      derived from "theory of mind" to predict key components of decision making in
      high-functioning young adults on the autism spectrum. A battery of tests was
      administered to 15 high-functioning college students with autism spectrum
      disorder (ASD), focusing on decision making competence (DMC) and other aspects of
      decision making related to known deficits associated with autism. Data from this
      group were compared to data from unselected college students receiving the same
      measures. First, as a test of a key social deficit associated with autism, the
      target group scored much lower on the Empathy Quotient scale. Traditional
      elements of decision making competency such as Numeracy and application of
      decision rules were comparable across groups. However, there were differences in
      thinking style, with the ASD group showing lesser ability and engagement in
      intuitive thinking, and they showed lower levels of risk taking. For comparisons
      within the ASD group, autobiographical reports concerning individual lifestyles
      and outcomes were used to derive a scale of Social Functioning. The lowest
      scoring individuals showed the lowest levels of intuitive thinking, the lowest
      perceived levels of others' endorsement of socially undesirable behaviors, and
      the lowest ability to discriminate between "good" and "bad" risks. Results are
      discussed in terms of interventions that might aid high-functioning young adults
      with ASD in their everyday decision making. 

PMID- 25972832
TI  - Illusory visual motion stimulus elicits postural sway in migraine patients.
AB  - Although the perception of visual motion modulates postural control, it is
      unknown whether illusory visual motion elicits postural sway. The present study
      examined the effect of illusory motion on postural sway in patients with
      migraine, who tend to be sensitive to it. We measured postural sway for both
      migraine patients and controls while they viewed static visual stimuli with and
      without illusory motion. The participants' postural sway was measured when they
      closed their eyes either immediately after (Experiment 1), or 30 s after
      (Experiment 2), viewing the stimuli. The patients swayed more than the controls
      when they closed their eyes immediately after viewing the illusory motion
      (Experiment 1), and they swayed less than the controls when they closed their
      eyes 30 s after viewing it (Experiment 2). These results suggest that static
      visual stimuli with illusory motion can induce postural sway that may last for at
      least 30 s in patients with migraine. 

PMID- 25972834
TI  - Meal replacement and functional connectivity in the brain network for appetite:
      connecting the dots.

PMID- 25972833
TI  - Performance-based tests versus behavioral ratings in the assessment of executive
      functioning in preschoolers: associations with ADHD symptoms and reading
      achievement.
AB  - The early assessment of the executive processes using ecologically valid
      instruments is essential for identifying deficits and planning actions to deal
      with possible adverse consequences. The present study has two different
      objectives. The first objective is to analyze the relationship between
      preschoolers' performance on tests of Working Memory and Inhibition and parents'
      and teachers' ratings of these executive functions (EFs) using the Behavior
      Rating Inventory of Executive Function (BRIEF). The second objective consists of
      studying the predictive value of the different EF measures (performance-based
      test and rating scales) on Inattention and Hyperactivity/Impulsivity behaviors
      and on indicators of word reading performance. The participants in the study were
      209 children in the last year of preschool, their teachers and their families.
      Performance-based tests of Working Memory and Inhibition were administered, as
      well as word reading measures (accuracy and speed). The parents and teachers
      filled out rating scales of the EF and typical behaviors of attention deficit
      hyperactivity disorder (ADHD) symptomatology. Moderate correlation values were
      found between the different EF assessments procedures, although the results
      varied depending on the different domains. Metacognition Index from the BRIEF
      presented stronger correlations with verbal working memory tests than with
      inhibition tests. Both the rating scales and the performance-based tests were
      significant predictors of Inattention and Hyperactivity/Impulsivity behaviors and
      the reading achievement measures. However, the BRIEF explained a greater
      percentage of variance in the case of the ADHD symptomatology, while the
      performance-based tests explained reading achievement to a greater degree. The
      implications of the findings for research and clinical practice are discussed. 

PMID- 25972835
TI  - Commentary on: "Motor Switching and Motor Adaptation Deficits Contribute to
      Freezing of Gait in Parkinson's Disease".

PMID- 25972836
TI  - Gap-Prepulse Inhibition of the Acoustic Startle Reflex (GPIAS) for Tinnitus
      Assessment: Current Status and Future Directions.
AB  - The progress in the field of tinnitus largely depends on the development of a
      reliable tinnitus animal model. Recently, a new method based on the acoustic
      startle reflex modification was introduced for tinnitus screening in laboratory
      animals. This method was enthusiastically adopted and now widely used by many
      scientists in the field due to its seeming simplicity and a number of advantages
      over the other methods of tinnitus assessment. Furthermore, this method opened an
      opportunity for tinnitus assessment in humans as well. Unfortunately, multiple
      modifications of data collection and interpretation implemented in different labs
      make comparisons across studies very difficult. In addition, recent animal and
      human studies have challenged the original "filling-in" interpretation of the
      paradigm. Here, we review the current literature to emphasize on the
      commonalities and differences in data collection and interpretation across
      laboratories that are using this method for tinnitus assessment. We also propose
      future research directions that could be taken in order to establish whether or
      not this method is warranted as an indicator of the presence of tinnitus. 

PMID- 25972837
TI  - DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid
      biosynthesis associated with depression and suicide risk.
AB  - Polyunsaturated fatty acid (PUFA) status has been associated with
      neuropsychiatric disorders, including depression and risk of suicide. Long-chain
      PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation
      and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6)
      and alpha-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in
      genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n
      = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched
      healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA
      biosynthesis pathway were determined by transesterification and gas
      chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic
      genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very
      long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite
      pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt
      status did not survive correction for multiple testing. However, MDD diagnosis
      and suicide attempts were significantly associated with DNA methylation in Elovl5
      gene regulatory regions. Also the relative roles of PUFA levels and DNA
      methylation with respect to diagnostic and suicide attempt status were determined
      by least absolute shrinkage and selection operator logistic regression analyses.
      We found that PUFA associations with suicide attempt status were explained by
      effects of Elovl5 DNA methylation within the regulatory regions. The observed
      link between plasma PUFA levels, DNA methylation, and suicide risk may have
      implications for modulation of disease-associated epigenetic marks by nutritional
      intervention. 

PMID- 25972838
TI  - Effect of topical anti-glaucoma medications on late pupillary light reflex, as
      evaluated by pupillometry.
AB  - PURPOSE: The late post-illumination pupillary response (PIPR 10-30s ) to blue
      light is reduced in glaucoma, suggesting that pupillometry can be used in
      clinical glaucoma evaluation. Since animal studies have indicated that common
      anti-glaucomatous agents affect the iris muscle, we investigated the short-term
      effect of the anti-glaucoma drugs on the pupillary light reflex and in particular
      on the PIPR10-30s. METHODS: In this randomized, double-masked, crossover trial,
      pupillometry was performed before and after topical administration of
      latanoprost, dorzolamide, and timolol in 20 healthy subjects. Stimulus was blue
      (463 nm) and red light (633 nm) of 2 log (lux). Main outcome was the PIPR10-30s
      to blue light. Additionally, pupil size, maximal contraction, and the early post
      illumination pupillary response (PIPR 0-10s ) to blue and red light were
      investigated. Pupil response variations between 8 a.m. and 2 p.m. were also
      assessed. Intraocular pressure (IOP) was measured before and 3.5 h after drug
      instillation. RESULTS: We found no drug effect on the blue light PIPR10-30s or
      any other blue light pupil parameters. During the control day, the only
      significant variation over time was observed for the red light PIPR0-10s (p =
      0.02). Pupillary size decreased slightly with timolol (0.1 mm, p = 0.03) and
      dorzolamide (0.2 mm, p < 0.001), but not with latanoprost. Timolol also reduced
      the maximal contraction amplitude significantly during red light (p = 0.02).
      Intraocular pressure was significantly reduced by all three drugs after 3.5 h (p
      < 0.01), while it remained unchanged during the control day (p = 0.3).
      CONCLUSION: Anti-glaucoma medications did not interfere with the blue light
      elicited PIPR. Dorzolamide reduced pupil size, while timolol reduced both pupil
      size and maximal contraction to red light, but the effect was minute and not of
      clinical importance.

PMID- 25972839
TI  - Editorial: Variation in Phase II Metabolism of Sex Steroids - Causes and
      Consequences.

PMID- 25972840
TI  - Pathway Regulation of p63, a Director of Epithelial Cell Fate.
AB  - The p53-related gene p63 is required for epithelial cell establishment and its
      expression is often altered in tumor cells. Great strides have been made in
      understanding the pathways and mechanisms that regulate p63 levels, such as the
      Wnt, Hedgehog, Notch, and EGFR pathways. We discuss here the multiple signaling
      pathways that control p63 expression as well as transcription factors and post
      transcriptional mechanisms that regulate p63 levels. While a unified picture has
      not emerged, it is clear that the fine-tuning of p63 has evolved to carefully
      control epithelial cell differentiation and fate. 

PMID- 25972842
TI  - Enhancement of antibiotic activity by efflux inhibitors against multidrug
      resistant Mycobacterium tuberculosis clinical isolates from Brazil.
AB  - Drug resistant tuberculosis continues to increase and new approaches for its
      treatment are necessary. The identification of M. tuberculosis clinical isolates
      presenting efflux as part of their resistant phenotype has a major impact in
      tuberculosis treatment. In this work, we used a checkerboard procedure combined
      with the tetrazolium microplate-based assay (TEMA) to study single combinations
      between antituberculosis drugs and efflux inhibitors (EIs) against multidrug
      resistant M. tuberculosis clinical isolates using the fully susceptible strain
      H37Rv as reference. Efflux activity was studied on a real-time basis by a
      fluorometric method that uses ethidium bromide as efflux substrate.
      Quantification of efflux pump genes mRNA transcriptional levels were performed by
      RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic
      activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin,
      and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The
      FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64
      fold reduction. The detection of active efflux by real-time fluorometry showed
      that all strains presented intrinsic efflux activity that contributes to the
      overall resistance which can be inhibited in the presence of the EIs. The
      quantification of the mRNA levels of the most important efflux pump genes on
      these strains shows that they are intrinsically predisposed to expel toxic
      compounds as the exposure to subinhibitory concentrations of antibiotics were not
      necessary to increase the pump mRNA levels when compared with the non-exposed
      counterpart. The results obtained in this study confirm that the intrinsic efflux
      activity contributes to the overall resistance in multidrug resistant clinical
      isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs
      can enhance the clinical effect of antibiotics that are their substrates. 

PMID- 25972841
TI  - Central oxytocin and food intake: focus on macronutrient-driven reward.
AB  - Centrally acting oxytocin (OT) is known to terminate food consumption in response
      to excessive stomach distension, increase in salt loading, and presence of
      toxins. Hypothalamic-hindbrain OT pathways facilitate these aspects of OT-induced
      hypophagia. However, recent discoveries have implicated OT in modifications of
      feeding via reward circuits: OT has been found to differentially affect
      consumption of individual macronutrients in choice and no-choice paradigms. In
      this mini-review, we focus on presenting and interpreting evidence that defines
      OT as a key component of mechanisms that reduce eating for pleasure and shape
      macronutrient preferences. We also provide remarks on challenges in integrating
      the knowledge on physiological and pathophysiological states in which both OT
      activity and macronutrient preferences are affected. 

PMID- 25972843
TI  - Characterization of MtoD from Sideroxydans lithotrophicus: a cytochrome c
      electron shuttle used in lithoautotrophic growth.
AB  - The autotrophic Sideroxydans lithotrophicus ES-1 can grow by coupling the
      oxidation of ferrous iron to the reduction of oxygen. Soluble ferrous iron is
      oxidized at the surface of the cell by an MtoAB porin-cytochrome complex that
      functions as an electron conduit through the outer membrane. Electrons are then
      transported to the cytoplasmic membrane where they are used to generate proton
      motive force (PMF) (for ATP synthesis) and NADH for autotrophic processes such as
      carbon fixation. As part of the mtoAB gene cluster, S. lithotrophicus also
      contains the gene mtoD that is proposed to encode a cytochrome c protein. We
      isolated mtoD from a Shewanella oneidensis expression system where the mtoD gene
      was expressed on a pBAD plasmid vector. Biochemical, biophysical, and
      crystallographic characterization of the purified MtoD revealed it as an 11 kDa
      monomeric protein containing a single heme. Sequence and structural alignment
      indicated that MtoD belonged to the class-1 cytochrome c family and had a similar
      fold to ferricytochrome c552 family, however the MtoD heme is bis-histidine
      coordinated and is substantially more exposed than the hemes of other family
      members. The reduction potential of the MtoD heme at pH 7 was +155 mV vs.
      Standard Hydrogen Electrode, which is approximately 100 mV lower than that of
      mitochondrial cytochrome c. Consideration of the properties of MtoD in the
      context of the potential respiratory partners identified from the genome suggests
      that MtoD could associate to multiple electron transfer partners as the primary
      periplasmic electron shuttle. 

PMID- 25972844
TI  - Detection of multi-drug resistant Escherichia coli in the urban waterways of
      Milwaukee, WI.
AB  - Urban waterways represent a natural reservoir of antibiotic resistance which may
      provide a source of transferable genetic elements to human commensal bacteria and
      pathogens. The objective of this study was to evaluate antibiotic resistance of
      Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to
      those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics
      covering 10 different families were utilized to determine the phenotypic
      antibiotic resistance for all 259 E. coli isolates. All obtained isolates were
      determined to be multi-drug resistant. The E. coli isolates were also screened
      for the presence of the genetic determinants of resistance including ermB
      (macrolide resistance), tet(M) (tetracycline resistance), and beta-lactamases
      (bla OXA, bla SHV, and bla PSE). E. coli from urban waterways showed a greater
      incidence of antibiotic resistance to 8 of 17 antibiotics tested compared to
      human derived sources. These E. coli isolates also demonstrated a greater
      incidence of resistance to higher numbers of antibiotics compared to the human
      derived isolates. The urban waterways demonstrated a greater abundance of
      isolates with co-occurrence of antibiotic resistance than human derived sources.
      When screened for five different antibiotic resistance genes conferring
      macrolide, tetracycline, and beta-lactam resistance, clinical E. coli isolates
      were more likely to harbor ermB and bla OXA than isolates from urban waterway.
      These results indicate that Milwaukee's urban waterways may select or allow for a
      greater incidence of multiple antibiotic resistance organisms and likely harbor a
      different antibiotic resistance gene pool than clinical sources. The implications
      of this study are significant to understanding the presence of resistance in
      urban freshwater environments by supporting the idea that sediment from urban
      waterways serves as a reservoir of antibiotic resistance. 

PMID- 25972845
TI  - Intra-domain phage display (ID-PhD) of peptides and protein mini-domains censored
      from canonical pIII phage display.
AB  - In this paper, we describe multivalent display of peptide and protein sequences
      typically censored from traditional N-terminal display on protein pIII of
      filamentous bacteriophage M13. Using site-directed mutagenesis of commercially
      available M13KE phage cloning vector, we introduced sites that permit efficient
      cloning using restriction enzymes between domains N1 and N2 of the pIII protein.
      As infectivity of phage is directly linked to the integrity of the connection
      between N1 and N2 domains, intra-domain phage display (ID-PhD) allows for simple
      quality control of the display and the natural variations in the displayed
      sequences. Additionally, direct linkage to phage propagation allows efficient
      monitoring of sequence cleavage, providing a convenient system for selection and
      evolution of protease-susceptible or protease-resistant sequences. As an example
      of the benefits of such an ID-PhD system, we displayed a negatively charged FLAG
      sequence, which is known to be post-translationally excised from pIII when
      displayed on the N-terminus, as well as positively charged sequences which
      suppress production of phage when displayed on the N-terminus. ID-PhD of FLAG
      exhibited sub-nanomolar apparent Kd suggesting multivalent nature of the display.
      A TEV-protease recognition sequence (TEVrs) co-expressed in tandem with FLAG,
      allowed us to demonstrate that 99.9997% of the phage displayed the FLAG-TEVrs
      tandem and can be recognized and cleaved by TEV-protease. The residual 0.0003%
      consisted of phage clones that have excised the insert from their genome. ID-PhD
      is also amenable to display of protein mini-domains, such as the 33-residue
      minimized Z-domain of protein A. We show that it is thus possible to use ID-PhD
      for multivalent display and selection of mini-domain proteins (Affibodies, scFv,
      etc.). 

PMID- 25972846
TI  - Identification of giant Mimivirus protein functions using RNA interference.
AB  - Genomic analysis of giant viruses, such as Mimivirus, has revealed that more than
      half of the putative genes have no known functions (ORFans). We knocked down
      Mimivirus genes using short interfering RNA as a proof of concept to determine
      the functions of giant virus ORFans. As fibers are easy to observe, we targeted a
      gene encoding a protein absent in a Mimivirus mutant devoid of fibers as well as
      three genes encoding products identified in a protein concentrate of fibers,
      including one ORFan and one gene of unknown function. We found that knocking down
      these four genes was associated with depletion or modification of the fibers. Our
      strategy of silencing ORFan genes in giant viruses opens a way to identify its
      complete gene repertoire and may clarify the role of these genes, differentiating
      between junk DNA and truly used genes. Using this strategy, we were able to
      annotate four proteins in Mimivirus and 30 homologous proteins in other giant
      viruses. In addition, we were able to annotate >500 proteins from cellular
      organisms and 100 from metagenomic databases. 

PMID- 25972847
TI  - What should be considered if you decide to build your own mathematical model for
      predicting the development of bacterial resistance? Recommendations based on a
      systematic review of the literature.
AB  - Acquired bacterial resistance is one of the causes of mortality and morbidity
      from infectious diseases. Mathematical modeling allows us to predict the spread
      of resistance and to some extent to control its dynamics. The purpose of this
      review was to examine existing mathematical models in order to understand the
      pros and cons of currently used approaches and to build our own model. During the
      analysis, seven articles on mathematical approaches to studying resistance that
      satisfied the inclusion/exclusion criteria were selected. All models were
      classified according to the approach used to study resistance in the presence of
      an antibiotic and were analyzed in terms of our research. Some models require
      modifications due to the specifics of the research. The plan for further work on
      model building is as follows: modify some models, according to our research,
      check all obtained models against our data, and select the optimal model or
      models with the best quality of prediction. After that we would be able to build
      a model for the development of resistance using the obtained results. 

PMID- 25972848
TI  - Identification of signatory secondary metabolites during mycoparasitism of
      Rhizoctonia solani by Stachybotrys elegans.
AB  - Stachybotrys elegans is able to parasitize the fungal plant pathogen Rhizoctonia
      solani AG-3 following a complex and intimate interaction, which, among others,
      includes the production of cell wall-degrading enzymes, intracellular
      colonization, and expression of pathogenic process encoding genes. However,
      information on the metabolome level is non-existent during mycoparasitism. Here,
      we performed a direct-infusion mass spectrometry (DIMS) metabolomics analysis
      using an LTQ Orbitrap analyzer in order to detect changes in the profiles of
      induced secondary metabolites of both partners during this mycoparasitic
      interaction 4 and 5 days following its establishment. The diketopiperazine(s)
      (DKPs) cyclo(S-Pro-S-Leu)/cyclo(S-Pro-S-Ile), ethyl 2-phenylacetate, and 3-nitro
      4-hydroxybenzoic acid were detected as the primary response of Rhizoctonia 4 days
      following dual-culturing with Stachybotrys, whereas only the latter metabolite
      was up-regulated 1 day later. On the other hand, trichothecenes and atranones
      were mycoparasite-derived metabolites identified during mycoparasitism 4 and 5
      days following dual-culturing. All the above secondary metabolites are known to
      exhibit bioactivity, including fungitoxicity, and represent key elements that
      determine the outcome of the interaction being studied. Results could be further
      exploited in programs for the evaluation of the bioactivity of these metabolites
      per se or their chemical analogs, and/or genetic engineering programs to obtain
      more efficient mycoparasite strains with improved efficacy and toxicological
      profiles. 

PMID- 25972849
TI  - PrhN, a putative marR family transcriptional regulator, is involved in positive
      regulation of type III secretion system and full virulence of Ralstonia
      solanacearum.
AB  - The MarR-family of transcriptional regulators are involved in various cellular
      processes, including resistance to multiple antibiotics and other toxic
      chemicals, adaptation to different environments and pathogenesis in many plant
      and animal pathogens. Here, we reported a new MarR regulator PrhN, which was
      involved in the pathogenesis of Ralstonia solanacearum. prhN mutant exhibited
      significantly reduced virulence and stem colonization compared to that of wild
      type in tomato plants. prhN mutant caused identical hypersensitive response (HR)
      on resistant plants to the wild type. Deletion of prhN gene substantially reduced
      the expression of type III secretion system (T3SS) in vitro and in planta (mainly
      in tomato plants), which is essential for pathogenicity of R. solanacearum, and
      the complemented PrhN could restore its virulence and T3SS expression to that of
      wild type. T3SS is directly controlled by AraC-type transcriptional regulator
      HrpB, and the transcription of hrpB is activated by HrpG and PrhG. HrpG and PrhG
      are homologs but are regulated by the PhcA positively and negatively,
      respectively. Deletion of prhN gene also abolished the expression of hrpB and
      prhG, but didn't change the expression of hrpG and phcA. Together, these results
      indicated that PrhN positively regulates T3SS expression through PrhG and HrpB.
      PrhN and PhcA should regulate prhG expression in a parallel way. This is the
      first report on the pathogenesis of MarR regulator in R. solanacearum, and this
      new finding will improve our understanding on the various biological functions of
      MarR regulator and the complex regulatory network on hrp regulon in R.
      solanacearum. 

PMID- 25972850
TI  - Comparison of alpha-glucosyl hesperidin of citrus fruits and epigallocatechin
      gallate of green tea on the Loss of Rotavirus Infectivity in Cell Culture.
AB  - A number of secondary plant metabolites (e.g., flavonoids) possess
      antiviral/antimicrobial activity. Most flavonoids, however, are difficult to
      study, as they are immiscible in water-based systems. The relatively new
      semisynthetic alpha-glucosyl hesperitin (GH), and the natural plant product
      epigallocatechin gallate (EGCG) are unique among most flavonoids, as these
      flavonoids are highly soluble. The antiviral activity of these plant metabolites
      were investigated using the rotavirus as a model enteric virus system. Direct
      loss of virus structural integrity in cell-free suspension and titration of
      amplified RTV in host cell cultures was measured by a quantitative enzyme-linked
      immunosorbent assay (qEIA). After 30 min. 100 * 10(3) MUg/ml GH reduced RTV
      antigen levels by ca. 90%. The same compound reduced infectivity (replication in
      cell culture) by a similar order of magnitude 3 to 4 days post inoculation. After
      3 days in culture, EGCG concentrations of 80, 160, and 320 MUg/ml reduced RTV
      infectivity titer levels to ca. 50, 20, and 15% of the control, respectively.
      Loss of RTV infectivity titers occurred following viral treatment by parallel
      testing of both GH and EGCG, with the latter, markedly more effective.
      Cytotoxicity testing showed no adverse effects by the phenolic concentrations
      used in this study. The unique chemical structure of each flavonoid rather than
      each phenolic's inherent solubility may be ascribed to those marked differences
      between each molecule's antiviral (anti-RTV) effects. The solubility of EGCG and
      GH obviated our need to use potentially confounding or obfuscating carrier
      molecules (e.g., methanol, ethanol, DMSO) denoting our use of a pure system
      environ. Our work further denotes the need to address the unique chemical nature
      of secondary plant metabolites before any broad generalizations in flavonoid
      (antiviral) activity may be proposed. 

PMID- 25972851
TI  - Transcriptional activity of the giant barrel sponge, Xestospongia muta Holobiont:
      molecular evidence for metabolic interchange.
AB  - Compared to our understanding of the taxonomic composition of the symbiotic
      microbes in marine sponges, the functional diversity of these symbionts is
      largely unknown. Furthermore, the application of genomic, transcriptomic, and
      proteomic techniques to functional questions on sponge host-symbiont interactions
      is in its infancy. In this study, we generated a transcriptome for the host and a
      metatranscriptome of its microbial symbionts for the giant barrel sponge,
      Xestospongia muta, from the Caribbean. In combination with a gene-specific
      approach, our goals were to (1) characterize genetic evidence for nitrogen
      cycling in X. muta, an important limiting nutrient on coral reefs (2) identify
      which prokaryotic symbiont lineages are metabolically active and, (3)
      characterize the metabolic potential of the prokaryotic community. Xestospongia
      muta expresses genes from multiple nitrogen transformation pathways that when
      combined with the abundance of this sponge, and previous data on dissolved
      inorganic nitrogen fluxes, shows that this sponge is an important contributor to
      nitrogen cycling biogeochemistry on coral reefs. Additionally, we observed
      significant differences in gene expression of the archaeal amoA gene, which is
      involved in ammonia oxidation, between coral reef locations consistent with
      differences in the fluxes of dissolved inorganic nitrogen previously reported. In
      regards to symbiont metabolic potential, the genes in the biosynthetic pathways
      of several amino acids were present in the prokaryotic metatranscriptome dataset
      but in the host-derived transcripts only the catabolic reactions for these amino
      acids were present. A similar pattern was observed for the B vitamins
      (riboflavin, biotin, thiamin, cobalamin). These results expand our understanding
      of biogeochemical cycling in sponges, and the metabolic interchange highlighted
      here advances the field of symbiont physiology by elucidating specific metabolic
      pathways where there is high potential for host-prokaryote interactions. 

PMID- 25972852
TI  - Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a
      long-term antibacterial activity in vitro against clinical isolates of
      Staphylococcus epidermidis.
AB  - Nowadays, the alarming rise in multidrug-resistant microorganisms urgently
      demands for suitable alternatives to current antibiotics. In this regard,
      antimicrobial peptides (AMPs) have received growing interest due to their broad
      spectrum of activities, potent antimicrobial properties, unique mechanisms of
      action, and low tendency to induce resistance. However, their pharmaceutical
      development is hampered by potential toxicity, relatively low stability and
      manufacturing costs. In the present study, we tested the hypothesis that the
      encapsulation of the frog-skin derived AMP temporin B (TB) into chitosan
      nanoparticles (CS-NPs) could increase peptide's antibacterial activity, while
      reducing its toxic potential. TB-loaded CS-NPs with good dimensional features
      were prepared, based on the ionotropic gelation between CS and sodium
      tripolyphosphate. The encapsulation efficiency of TB in the formulation was up to
      75%. Release kinetic studies highlighted a linear release of the peptide from the
      nanocarrier, in the adopted experimental conditions. Interestingly, the
      encapsulation of TB in CS-NPs demonstrated to reduce significantly the peptide's
      cytotoxicity against mammalian cells. Additionally, the nanocarrier evidenced a
      sustained antibacterial action against various strains of Staphylococcus
      epidermidis for at least 4 days, with up to 4-log reduction in the number of
      viable bacteria compared to plain CS-NPs at the end of the observational period.
      Of note, the antimicrobial evaluation tests demonstrated that while the intrinsic
      antimicrobial activity of CS ensured a "burst" effect, the gradual release of TB
      further reduced the viable bacterial count, preventing the regrowth of the
      residual cells and ensuring a long-lasting antibacterial effect. The developed
      nanocarrier is eligible for the administration of several AMPs of therapeutic
      interest with physical-chemical characteristics analog to those of TB. 

PMID- 25972853
TI  - Immersion infection of germ-free zebrafish with Listeria monocytogenes induces
      transient expression of innate immune response genes.
AB  - Zebrafish, Denio rerio, can be an alternative to other classic animal models for
      human infectious diseases to examine the processes of microbial infections and
      host-pathogen interactions in vivo because of their small body dimension but
      large clutch size. We established germ-free zebrafish infection models of
      Listeria monocytogenes through different routes of infection: oral immersion and
      injection via yolk sac, brain ventricle and blood island. Immersion of zebrafish
      larva even with 10(10) CFU/mL L. monocytogenes EGDe strain in egg water was
      unable to cause mortality, but GFP-expressing bacteria in the gut lumen can be
      observed in frozen sections. Several selected maker genes of the innate immune
      system, including cyp1a, irg1l, il1b, and mmp9, were significantly induced by
      oral immersion not only with strain EGDe, but also with strain M7 and L. innocua,
      though to a lesser degree (P < 0.01). Such induction appears to be transient with
      peak at 48 h post-infection, but returned to basal level at 72 h post-infection.
      Of the three injection routes, mortality after infection by yolk sac was 80% in
      early stage of infection. Few eggs can survive and hatch. Injection into
      zebrafish embryos via brain ventricle or blood island led to progressive lethal
      infection. L. mocytogenes EGDe showed steady replication in the fish embryos and
      was far more pathogenic than strain M7, which is consistent with findings in the
      murine model. We conclude that zebrafish can serve as susceptible and
      microscopically visible infection models for L. monocytogenes via different
      routes and can be applied to further studies on the interactions between
      bacterial virulence factors and host immune responses. 

PMID- 25972855
TI  - Diversity and comparative genomics of Microviridae in Sphagnum- dominated
      peatlands.
AB  - Microviridae, a family of bacteria-infecting ssDNA viruses, is one of the still
      poorly characterized bacteriophage groups, even though it includes phage PhiX174,
      one of the main models in virology for genomic and capsid structure studies.
      Recent studies suggest that they are diverse and well represented in marine and
      freshwater virioplankton as well as in human microbiomes. However, their
      diversity, abundance, and ecological role are completely unknown in soil
      ecosystems. Here we present the comparative analysis of 17 completely assembled
      Microviridae genomes from 12 viromes of a Sphagnum-dominated peatland.
      Phylogenetic analysis of the conserved major capsid protein sequences revealed
      the affiliation to Gokushovirinae and Pichovirinae as well as to two newly
      defined subfamilies, the Aravirinae and Stokavirinae. Additionally, two new
      distinct prophages were identified in the genomes of Parabacteroides merdae and
      Parabacteroides distasonis representing a potential new subfamily of
      Microviridae. The differentiation of the subfamilies was confirmed by gene order
      and similarity analysis. Relative abundance analysis using the affiliation of the
      major capsid protein (VP1) revealed that Gokushovirinae, followed by Aravirinae,
      are the most abundant Microviridae in 11 out of 12 peat viromes. Sequences
      matching the Gokushovirinae and Aravirinae VP1 matching sequences, respectively,
      accounted for up to 4.19 and 0.65% of the total number of sequences in the
      corresponding virome, respectively. In this study we provide new genome
      information of Microviridae and pave the way toward quantitative estimations of
      Microviridae subfamilies. 

PMID- 25972854
TI  - Endogenous generation of hydrogen sulfide and its regulation in Shewanella
      oneidensis.
AB  - Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a
      variety of functions across all domains of life. In this study, mechanisms of
      endogenous H2S generation in Shewanella oneidensis were investigated. As a
      research model with highly diverse anaerobic respiratory pathways, the
      microorganism is able to produce H2S by respiring on a variety of sulfur
      containing compounds with SirACD and PsrABC enzymatic complexes, as well as
      through cysteine degradation with three enzymes, MdeA, SO_1095, and SseA. We
      showed that the SirACD and PsrABC complexes, which are predominantly, if not
      exclusively, responsible for H2S generation via respiration of sulfur species, do
      not interplay with each other. Strikingly, a screen for regulators controlling
      endogenous H2S generation by transposon mutagenesis identified global regulator
      Crp to be essential to all H2S-generating processes. In contrast, Fnr and Arc,
      two other global regulators that have a role in respiration, are dispensable in
      regulating H2S generation via respiration of sulfur species. Interestingly, Arc
      is involved in the H2S generation through cysteine degradation by repressing
      expression of the mdeA gene. We further showed that expression of the sirA and
      psrABC operons is subjected to direct regulation of Crp, but the mechanisms
      underlying the requirement of Crp for H2S generation through cysteine degradation
      remain elusive. 

PMID- 25972856
TI  - Resistance gene pool to co-trimoxazole in non-susceptible Nocardia strains.
AB  - The soil-borne pathogen Nocardia sp. causes severe cutaneous, pulmonary, and
      central nervous system infections. Against them, co-trimoxazole (SXT) constitutes
      the mainstay of antimicrobial therapy. However, some Nocardia strains show
      resistance to SXT, but the underlying genetic basis is unknown. We investigated
      the presence of genetic resistance determinants and class 1-3 integrons in 76 SXT
      resistant Nocardia strains by PCR and sequencing. By E test, these clinical
      strains showed SXT minimum inhibitory concentrations of >=32:608 mg/L (ratio of
      1:19 for trimethoprim: sulfamethoxazole). They belonged to 12 species, being the
      main representatives Nocardia farcinica (32%), followed by N. flavorosea (6.5%),
      N. nova (11.8%), N. carnea (10.5%), N. transvalensis (10.5%), and Nocardia sp.
      (6.5%). The prevalence of resistance genes in the SXT-resistant strains was as
      follows: sul1 and sul2 93.4 and 78.9%, respectively, dfrA(S1) 14.7%, blaTEM-1 and
      blaZ 2.6 and 2.6%, respectively, VIM-2 1.3%, aph(3')-IIIa 40.8%, ermA, ermB,
      mefA, and msrD 2.6, 77.6, 14.4, and 5.2%, respectively, and tet(O), tet(M), and
      tet(L) 48.6, 25.0, and 3.9%, respectively. Detected amino acid changes in GyrA
      were not related to fluoroquinolone resistance, but probably linked to species
      polymorphism. Class 1 and 3 integrons were found in 93.42 and 56.57% strains,
      respectively. Class 2 integrons and sul3 genes were not detected. Other
      mechanisms, different than dfrA(S1), dfrD, dfrF, dfrG, and dfrK, could explain
      the strong trimethoprim resistance shown by the other 64 strains. For first time,
      resistance determinants commonly found in clinically important bacteria were
      detected in Nocardia sp. sul1, sul2, erm(B), and tet(O) were the most prevalent
      in the SXT-resistant strains. The similarity in their resistome could be due to a
      common genetic platform, in which these determinants are co-transferred. 

PMID- 25972858
TI  - Modeling the indirect effect of Wolbachia on the infection dynamics of
      horizontally transmitted viruses.
AB  - Intracellular bacteria of the genus Wolbachia are widely distributed in
      arthropods. There is growing empirical evidence that Wolbachia directly interacts
      with viruses and other parasites inside the arthropod host, sometimes resulting
      in low or no pathogen replication. Previous theoretical studies showed that this
      direct effect of Wolbachia can result in a reduced virus prevalence (within the
      population), suggesting that Wolbachia could be used in the biological control of
      vector-borne diseases (e.g., dengue fever). However, Wolbachia might also
      indirectly affect virus dynamics because Wolbachia-induced reproductive
      phenotypes (cytoplasmic incompatibility or male killing) increase the larval
      mortality of hosts and thus alter the age structure of populations. We
      investigated this indirect effect using mathematical models with overlapping
      generations, and found the results to depend strongly on the host's life history.
      In general, the indirect effect can result in two different outcomes: (1) reduced
      virus prevalence and virus invasion ability, and (2) increased virus prevalence
      and virus invasion ability. The former occurs for host species with larval
      competition and undercompensation, the latter for hosts with either adult
      competition or larval competition and overcompensation. These findings suggest
      that the effect of Wolbachia on a specific virus is sensitive to the host's life
      history. We discuss the results with respect to biocontrol programs using
      Wolbachia. 

PMID- 25972857
TI  - RND-type drug efflux pumps from Gram-negative bacteria: molecular mechanism and
      inhibition.
AB  - Drug efflux protein complexes confer multidrug resistance on bacteria by
      transporting a wide spectrum of structurally diverse antibiotics. Moreover,
      organisms can only acquire resistance in the presence of an active efflux pump.
      The substrate range of drug efflux pumps is not limited to antibiotics, but it
      also includes toxins, dyes, detergents, lipids, and molecules involved in quorum
      sensing; hence efflux pumps are also associated with virulence and biofilm
      formation. Inhibitors of efflux pumps are therefore attractive compounds to
      reverse multidrug resistance and to prevent the development of resistance in
      clinically relevant bacterial pathogens. Recent successes on the structure
      determination and functional analysis of the AcrB and MexB components of the
      AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the
      fully assembled, functional triparted AcrAB-TolC complex significantly
      contributed to our understanding of the mechanism of substrate transport and the
      options for inhibition of efflux. These data, combined with the well-developed
      methodologies for measuring efflux pump inhibition, could allow the rational
      design, and subsequent experimental verification of potential efflux pump
      inhibitors (EPIs). In this review we will explore how the available biochemical
      and structural information can be translated into the discovery and development
      of new compounds that could reverse drug resistance in Gram-negative pathogens.
      The current literature on EPIs will also be analyzed and the reasons why no
      compounds have yet progressed into clinical use will be explored. 

PMID- 25972859
TI  - Genomes of sequence type 121 Listeria monocytogenes strains harbor highly
      conserved plasmids and prophages.
AB  - The food-borne pathogen Listeria (L.) monocytogenes is often found in food
      production environments. Thus, controlling the occurrence of L. monocytogenes in
      food production is a great challenge for food safety. Among a great diversity of
      L. monocytogenes strains from food production, particularly strains belonging to
      sequence type (ST)121 are prevalent. The molecular reasons for the abundance of
      ST121 strains are however currently unknown. We therefore determined the genome
      sequences of three L. monocytogenes ST121 strains: 6179 and 4423, which persisted
      for up to 8 years in food production plants in Ireland and Austria, and of the
      strain 3253 and compared them with available L. monocytogenes ST121 genomes. Our
      results show that the ST121 genomes are highly similar to each other and show a
      tremendously high degree of conservation among some of their prophages and
      particularly among their plasmids. This remarkably high level of conservation
      among prophages and plasmids suggests that strong selective pressure is acting on
      them. We thus hypothesize that plasmids and prophages are providing important
      adaptations for survival in food production environments. In addition, the ST121
      genomes share common adaptations which might be related to their persistence in
      food production environments such as the presence of Tn6188, a transposon
      responsible for increased tolerance against quaternary ammonium compounds, a yet
      undescribed insertion harboring recombination hotspot (RHS) repeat proteins,
      which are most likely involved in competition against other bacteria, and
      presence of homologs of the L. innocua genes lin0464 and lin0465. 

PMID- 25972860
TI  - Dissection of the cis-2-decenoic acid signaling network in Pseudomonas aeruginosa
      using microarray technique.
AB  - Many bacterial pathogens use quorum-sensing (QS) signaling to regulate the
      expression of factors contributing to virulence and persistence. Bacteria produce
      signals of different chemical classes. The signal molecule, known as diffusible
      signal factor (DSF), is a cis-unsaturated fatty acid that was first described in
      the plant pathogen Xanthomonas campestris. Previous works have shown that human
      pathogen, Pseudomonas aeruginosa, also synthesizes a structurally related
      molecule, characterized as cis-2-decenoic acid (C10: Delta(2), CDA) that induces
      biofilm dispersal by multiple types of bacteria. Furthermore, CDA has been shown
      to be involved in inter-kingdom signaling that modulates fungal behavior.
      Therefore, an understanding of its signaling mechanism could suggest strategies
      for interference, with consequences for disease control. To identify the
      components of CDA signaling pathway in this pathogen, a comparative transcritpome
      analysis was conducted, in the presence and absence of CDA. A protein-protein
      interaction (PPI) network for differentially expressed (DE) genes with known
      function was then constructed by STRING and Cytoscape. In addition, the effects
      of CDA in combination with antimicrobial agents on the biofilm surface area and
      bacteria viability were evaluated using fluorescence microscopy and digital image
      analysis. Microarray analysis identified 666 differentially expressed genes in
      the presence of CDA and gene ontology (GO) analysis revealed that in P.
      aeruginosa, CDA mediates dispersion of biofilms through signaling pathways,
      including enhanced motility, metabolic activity, virulence as well as persistence
      at different temperatures. PPI data suggested that a cluster of five genes
      (PA4978, PA4979, PA4980, PA4982, PA4983) is involved in the CDA synthesis and
      perception. Combined treatments using both CDA and antimicrobial agents showed
      that following exposure of the biofilms to CDA, remaining cells on the surface
      were easily removed and killed by antimicrobials. 

PMID- 25972861
TI  - Antibacterial activity of alkyl gallates is a combination of direct targeting of
      FtsZ and permeabilization of bacterial membranes.
AB  - Alkyl gallates are compounds with reported antibacterial activity. One of the
      modes of action is binding of the alkyl gallates to the bacterial membrane and
      interference with membrane integrity. However, alkyl gallates also cause cell
      elongation and disruption of cell division in the important plant pathogen
      Xanthomonas citri subsp. citri, suggesting that cell division proteins may be
      targeted by alkyl gallates. Here, we use Bacillus subtilis and purified B.
      subtilis FtsZ to demonstrate that FtsZ is a direct target of alkyl gallates.
      Alkyl gallates disrupt the FtsZ-ring in vivo, and cause cell elongation. In
      vitro, alkyl gallates bind with high affinity to FtsZ, causing it to cluster and
      lose its capacity to polymerize. The activities of a homologous series of alkyl
      gallates with alkyl side chain lengths ranging from five to eight carbons (C5-C8)
      were compared and heptyl gallate was found to be the most potent FtsZ inhibitor.
      Next to the direct effect on FtsZ, alkyl gallates also target B. subtilis
      membrane integrity-however the observed anti-FtsZ activity is not a secondary
      effect of the disruption of membrane integrity. We propose that both modes of
      action, membrane disruption and anti-FtsZ activity, contribute to the
      antibacterial activity of the alkyl gallates. We propose that heptyl gallate is a
      promising hit for the further development of antibacterials that specifically
      target FtsZ. 

PMID- 25972862
TI  - Host cell type-dependent translocation and PhoP-mediated positive regulation of
      the effector SseK1 of Salmonella enterica.
AB  - Salmonella enterica expresses two virulence-related type III secretion systems
      (T3SSs) encoded in Salmonella pathogenicity island 1 (SPI1) and SPI2,
      respectively. SseK1 is a poorly characterized substrate of the SPI2-encoded T3SS.
      Here, we show that this effector is essential to get full virulence both in oral
      and intraperitoneal mice infections, in spite of not having a role in invasion or
      intracellular proliferation in cultured mammalian cells. In vitro, expression of
      sseK1 was higher in media mimicking intracellular conditions, when SPI2 was
      induced, but it was also significant under SPI1 inducing conditions. A detailed
      analysis of translocation of SseK1 into host cells unveiled that it was a
      substrate of both, T3SS1 and T3SS2, although with different patterns and kinetics
      depending on the specific host cell type (epithelial, macrophages, or
      fibroblasts). The regulation of the expression of sseK1 was examined using lacZ
      and bioluminescent lux fusions. The two-component system PhoQ/PhoP is a positive
      regulator of this gene. A combination of sequence analysis, directed mutagenesis
      and electrophoretic mobility shift assays showed that phosphorylated PhoP binds
      directly to the promoter region of sseK1 and revealed a PhoP binding site located
      upstream of the predicted -35 hexamer of this promoter. 

PMID- 25972863
TI  - Seroepidemiology of Toxoplasmosis among People Having Close Contact with Animals.
AB  - A cross-sectional study was conducted to determine the seroepidemiology of
      Toxoplasma infection and its risk association among people having close contact
      with animals. A total of 312 blood samples were collected from veterinary
      personnel (veterinarian, technicians, and students) and pet owners from
      veterinary clinics and hospitals in the area of Klang Valley, Malaysia. About 4
      cc of blood samples drawn from agreed participants were processed for measurement
      of anti-Toxoplasma IgG and IgM antibodies as well as avidity test of Toxoplasma
      IgG by ELISA I, II, and III kits. Meanwhile, the demographic profiles and
      possible risk factors of these participants were also recorded in the
      standardized data collection sheets. Overall seroprevalence of toxoplasmosis was
      observed in 62 (19.9%) participants being 7 (18.4%) in veterinarians, 15 (33.3%)
      in veterinary technicians, 29 (14.9%) in veterinary students, and 11 (31.4%) in
      pet owners. Of 19.9% Toxoplasma seropositive samples, 18.3% was positive for IgG
      antibody, 1.0% for IgM antibody, and 0.6% for both IgG and IgM antibodies. Of
      three different IgG avidity ELISA kits, ELISA III showed high avidity in all five
      seropositive samples (IgM and IgG/IgM antibodies) indicating chronic Toxoplasma
      infection which is consistent with no evidence of clinical toxoplasmosis
      diagnosed during the time of this study. Univariate analysis showed that age
      group, gender, study population, gardening, task performance, and working
      duration were significantly associated with Toxoplasma seropositivity. Further
      analysis by multivariate analysis using logistic regression showed that age group
      of >=30 years old (OR = 0.34, 95% CI = 0.18-0.63, p = 0.001) and working or study
      duration of >10 years having close contact with animals (OR = 5.07, 95% CI = 1.80
      14.24, p = 0.002) were identified as significant risks for Toxoplasma infection.
      Based on the results obtained, a comprehensive Toxoplasma screening and health
      surveillance program on toxoplasmosis should be implemented among people having
      close contact with animals in general and confirmed Toxoplasma seronegative
      individuals in particular to prevent seroconversion. 

PMID- 25972864
TI  - Immune System Involvement in the Pathogenesis of JC Virus Induced PML: What is
      Learned from Studies of Patients with Underlying Diseases and Therapies as Risk
      Factors.
AB  - The human polyomavirus JC PyV lytic infection of oligodendrocytes in the human
      brain results in the demyelinating disease progressive multifocal
      leukoencephalopathy, PML. JCV is a common virus infection in the population that
      leads to PML in patients with underlying diseases and therapies that cause immune
      deficiencies or modulate immune system functions. Patients may have high levels
      of antibody to JCV that neither protect them from PML nor clear the infection
      once PML is established. Cell-mediated immunity plays a more effective role in
      clearing initial or reactivated JCV infection before PML occurs. However,
      patients with underlying diseases and therapies for treatment are at high risk
      for PML. MS patients on natalizumab are one of the categories with the highest
      incidence of PML. Natalizumab is a humanized monoclonal antibody targeting alpha4
      integrins that prevents inflammatory cells from entering the brain and it has
      been used as a treatment for MS. A number of studies have investigated the
      occurrence of PML in these patients and their cell-mediated immune profile that
      might gain insight into the mechanism that ties natalizumab with a high risk of
      developing PML. It seems that cells of the immune system participate in the
      pathogenesis of PML as well as clearance of JCV infection. 

PMID- 25972866
TI  - Strategies for building reference standards for autoantibodies.
AB  - Producing robust, certified, traceable reference material for autoantibody
      testing is a vital element in maintaining the validity of results that are
      generated in the daily clinical laboratory routine. This is a huge challenge
      because of the high number of variables involved in the detection and measurement
      of the autoantibodies. The production of such materials is time consuming and
      needs rigorous attention to detail; this is best achieved by an overarching
      independent body who will oversee the process in a "not for profit" manner. Much
      effort has been made to build international standards for quantitative and
      qualitative assays based on monoclonal antibodies, obtained from affinity
      purification and plasmapheresis. The big challenge is to respect individual
      differences in immune response to the same antigen. A promising ongoing
      initiative is the construction of pools with monospecific samples from different
      individuals. 

PMID- 25972865
TI  - Pseudotype-based neutralization assays for influenza: a systematic analysis.
AB  - The use of vaccination against the influenza virus remains the most effective
      method of mitigating the significant morbidity and mortality caused by this
      virus. Antibodies elicited by currently licensed influenza vaccines are
      predominantly hemagglutination-inhibition (HI)-competent antibodies that target
      the globular head of hemagglutinin (HA) thus inhibiting influenza virus entry
      into target cells. These antibodies predominantly confer homosubtypic/strain
      specific protection and only rarely confer heterosubtypic protection. However,
      recent academia or pharma-led R&D toward the production of a "universal vaccine"
      has centered on the elicitation of antibodies directed against the stalk of the
      influenza HA that has been shown to confer broad protection across a range of
      different subtypes (H1-H16). The accurate and sensitive measurement of antibody
      responses elicited by these "next-generation" influenza vaccines is, however,
      hampered by the lack of sensitivity of the traditional influenza serological
      assays HI, single radial hemolysis, and microneutralization. Assays utilizing
      pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to
      be highly efficient for the measurement of homosubtypic and heterosubtypic
      broadly neutralizing antibodies, making them ideal serological tools for the
      study of cross-protective responses against multiple influenza subtypes with
      pandemic potential. In this review, we will analyze and compare literature
      involving the production of influenza pseudotypes with particular emphasis on
      their use in serum antibody neutralization assays. This will enable us to
      establish the parameters required for optimization and propose a consensus
      protocol to be employed for the further deployment of these assays in influenza
      vaccine immunogenicity studies. 

PMID- 25972867
TI  - Utilizing chimeric antigen receptors to direct natural killer cell activity.
AB  - Natural killer (NK) cells represent an attractive lymphocyte population for
      cancer immunotherapy due to their ability to lyse tumor targets without prior
      sensitization and without need for human leukocyte antigens-matching. Chimeric
      antigen receptors (CARs) are able to enhance lymphocyte targeting and activation
      toward diverse malignancies. CARs consist of an external recognition domain
      (typically a small chain variable fragment) directed at a specific tumor antigen
      that is linked with one or more intracellular signaling domains that mediate
      lymphocyte activation. Most CAR studies have focused on their expression in T
      cells. However, use of CARs in NK cells is starting to gain traction because they
      provide a method to redirect these cells more specifically to target refractory
      cancers. CAR-mediated anti-tumor activity has been demonstrated using NK cell
      lines, as well as NK cells isolated from peripheral blood, and NK cells produced
      from human pluripotent stem cells. This review will outline the CAR constructs
      that have been reported in NK cells with a focus on comparing the use of
      different signaling domains in combination with other co-activating domains. 

PMID- 25972868
TI  - Single-Cell Characterization of in vitro Migration and Interaction Dynamics of T
      Cells Expanded with IL-2 and IL-7.
AB  - T cells are pivotal in the immune defense against cancers and infectious agents.
      To mount an effector response against cancer cells, T cells need to migrate to
      the cancer-site, engage in contacts with cancer cells, and perform their effector
      functions. Adoptive T cell therapy is an effective strategy as treatment of
      complications such as relapse or opportunistic infections after hematopoietic
      stem cell transplantations. This requires a sufficient amount of cells that are
      able to expand and respond to tumor or viral antigens. The cytokines interleukin
      (IL)-2 and IL-7 drive T cell differentiation, proliferation, and survival and are
      commonly used to expand T cells ex vivo. Here, we have used microchip-based live
      cell imaging to follow the migration of individual T cells, their interactions
      with allogeneic monocytes, cell division, and apoptosis for extended periods of
      time; something that cannot be achieved by commonly used methods. Our data
      indicate that cells grown in IL-7 + IL-2 had similar migration and contact
      dynamics as cells grown in IL-2 alone. However, the addition of IL-7 decreased
      cell death creating a more viable cell population, which should be beneficial
      when preparing cells for immunotherapy. 

PMID- 25972870
TI  - CD4(+) T Cell Differentiation in Infection: Amendments to the Th1/Th2 Axiom.

PMID- 25972869
TI  - Differences in Anti-Inflammatory Actions of Intravenous Immunoglobulin between
      Mice and Men: More than Meets the Eye.
AB  - Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific
      human IgGs purified from plasma pooled from thousands of individuals. When
      administered at a high dose, IVIg inhibits inflammation and has proven efficacy
      in the treatment of various autoimmune and systemic inflammatory diseases.
      Importantly, IVIg therapy can ameliorate both auto-antibody-mediated and T-cell
      mediated immune pathologies. In the last few decades, extensive research in
      murine disease models has resulted in the elucidation of two novel anti
      inflammatory mechanisms-of-action of IVIg: induction of FcgammaRIIB expression by
      sialylated Fc, and stimulation of regulatory T cells. Whereas controversial
      findings in mice studies have recently inspired intense scientific debate
      regarding the validity of the sialylated Fc-FcgammaRIIB model, the most
      fundamental question is whether these anti-inflammatory mechanisms of IVIg are
      operational in humans treated with IVIg. In this review, we examine the evidence
      for the involvement of these anti-inflammatory mechanisms in the therapeutic
      effects of IVIg in humans. We demonstrate that although several elements of both
      immune-modulatory pathways of IVIg are activated in humans, incorrect
      extrapolations from mice to men have been made on the molecular and cellular
      components involved in these cascades that warrant for critical re-evaluation of
      these anti-inflammatory mechanisms of IVIg in humans. 

PMID- 25972871
TI  - Of LAP, CUPS, and DRibbles - Unconventional Use of Autophagy Proteins for MHC
      Restricted Antigen Presentation.
AB  - Macroautophagy delivers cytoplasmic constituents for lysosomal degradation.
      Because MHC class II molecules are loaded with lysosomal products for CD4(+) T
      cell stimulation, macroautophagy supports intracellular antigen processing onto
      MHC class II molecules. The molecular machinery of macroautophagy, however, does
      not only support this autophagic antigen processing, but seems to also modify
      extracellular antigen uptake for MHC class II presentation, antigen exocytosis,
      and packaging for improved cross-presentation onto MHC class I molecules. The
      different membrane trafficking pathways with LC3-associated phagocytosis,
      compartment for unconventional protein secretion, and DRibbles as well as the
      role that autophagic proteins play in them will be discussed in this review. 

PMID- 25972873
TI  - Neuroimmunology: an expanding frontier in autoimmunity.
AB  - Anti-neuronal autoimmune encephalitis (AIE) comprises a recently characterized
      group of immune-mediated disorders that result in limbic, multifocal, or diffuse
      encephalitis due to direct interaction of autoantibodies with neuronal surface or
      synaptic proteins. The pathological effects of the autoantibodies vary according
      to the target antigen but when they are removed, neuronal dysfunction is commonly
      reversed. Ongoing research on AIE constantly increases the number of novel
      autoantibodies and expands the spectrum of neurological syndromes that are
      important in the differential diagnosis of psychiatric illness, dementia, or
      viral encephalitis. This review summarizes recent advances in AIE, focusing on
      pathogenetic mechanisms and novel associations with other CNS disorders such as
      neurodegeneration, relapsing symptoms post-herpes simplex virus encephalitis, and
      demyelinating diseases. In addition, an algorithmic approach to detect and
      characterize neuronal cell surface autoantibodies is proposed. 

PMID- 25972874
TI  - AS03-Adjuvanted, Very-Low-Dose Influenza Vaccines Induce Distinctive Immune
      Responses Compared to Unadjuvanted High-Dose Vaccines in BALB/c Mice.
AB  - During the 2009-2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was
      recommended for most Canadians. We hypothesize that differences exist in the
      responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full
      dose vaccines. We investigated the relationship between Ag dose and the oil-in
      water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A
      or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion
      vaccine Ag. Immune responses were assessed 3 weeks after the booster.
      Unadjuvanted "high" (3 MUg) and low-dose (0.03-0.003 MUg) vaccines generated
      similar serum antibody titers and cytokine secretion patterns in restimulated
      splenocytes. Compared to unadjuvanted "high-dose" vaccination, both AS03A and
      AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers,
      broader induction of cytokine secretion and generated more influenza-specific
      antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in
      splenocytes. We show that varying Ag and/or AS03 dose in this influenza
      vaccination mouse model can strongly influence both the magnitude and pattern of
      the immune response elicited. These findings are highly relevant given the
      likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise
      questions about the use of "standard" doses of vaccines in pre-clinical vaccine
      studies. 

PMID- 25972875
TI  - Salt tolerance at single cell level in giant-celled Characeae.
AB  - Characean plants provide an excellent experimental system for electrophysiology
      and physiology due to: (i) very large cell size, (ii) position on phylogenetic
      tree near the origin of land plants and (iii) continuous spectrum from very salt
      sensitive to very salt tolerant species. A range of experimental techniques is
      described, some unique to characean plants. Application of these methods provided
      electrical characteristics of membrane transporters, which dominate the membrane
      conductance under different outside conditions. With this considerable background
      knowledge the electrophysiology of salt sensitive and salt tolerant genera can be
      compared under salt and/or osmotic stress. Both salt tolerant and salt sensitive
      Characeae show a rise in membrane conductance and simultaneous increase in Na(+)
      influx upon exposure to saline medium. Salt tolerant Chara longifolia and
      Lamprothamnium sp. exhibit proton pump stimulation upon both turgor decrease and
      salinity increase, allowing the membrane PD to remain negative. The turgor is
      regulated through the inward K(+) rectifier and 2H(+)/Cl(-) symporter.
      Lamprothamnium plants can survive in hypersaline media up to twice seawater
      strength and withstand large sudden changes in salinity. Salt sensitive C.
      australis succumbs to 50-100 mM NaCl in few days. Cells exhibit no pump
      stimulation upon turgor decrease and at best transient pump stimulation upon
      salinity increase. Turgor is not regulated. The membrane PD exhibits
      characteristic noise upon exposure to salinity. Depolarization of membrane PD to
      excitation threshold sets off trains of action potentials, leading to further
      loses of K(+) and Cl(-). In final stages of salt damage the H(+)/OH(-) channels
      are thought to become the dominant transporter, dissipating the proton gradient
      and bringing the cell PD close to 0. The differences in transporter
      electrophysiology and their synergy under osmotic and/or saline stress in salt
      sensitive and salt tolerant characean cells are discussed in detail. 

PMID- 25972872
TI  - Therapeutic potential and challenges of natural killer cells in treatment of
      solid tumors.
AB  - Natural killer (NK) cells are innate lymphoid cells that hold tremendous
      potential for effective immunotherapy for a broad range of cancers. Due to the
      mode of NK cell killing, requiring one-to-one target engagement and site-directed
      release of cytolytic granules, the therapeutic potential of NK cells has been
      most extensively explored in hematological malignancies. However, their ability
      to precisely kill antibody coated cells, cancer stem cells, and genotoxically
      altered cells, while maintaining tolerance to healthy cells makes them appealing
      therapeutic effectors for all cancer forms, including metastases. Due to their
      release of pro-inflammatory cytokines, NK cells may potently reverse the anti
      inflammatory tumor microenvironment (TME) and augment adaptive immune responses
      by promoting differentiation, activation, and/or recruitment of accessory immune
      cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms
      of subversion of NK cell activity against the tumor and its microenvironment
      exist. Although our understanding of the receptor ligand interactions that
      regulate NK cell functionality has evolved remarkably, the diversity of ligands
      and receptors is complex, as is their mechanistic foundations in regulating NK
      cell function. In this article, we review the literature and highlight how the
      TME manipulates the NK cell phenotypes, genotypes, and tropism to evade tumor
      recognition and elimination. We discuss counter strategies that may be adopted to
      augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that
      have been undertaken so far in solid malignancies, critically weighing the
      challenges and opportunities with this approach. 

PMID- 25972876
TI  - Computed tomography scanning can monitor the effects of soil medium on root
      system development: an example of salt stress in corn.
AB  - Seeds and young seedlings often encounter high soluble salt levels in the upmost
      soil layers, impeding vigorous growth by affecting root establishment. Computed
      tomography (CT) scanning used at low X-ray doses can help study root development
      in such conditions non-destructively, because plants are allowed to grow
      throughout the experiment. Using a high-resolution Toshiba XVision CT scanner, we
      studied corn (Zea mays L.) root growth under optimal and salt-stressed conditions
      in 3D and on a weekly basis over 3 weeks. Two groups of three corn plants were
      grown in the controlled environment of a growth chamber, in mid-sized plastic
      pots filled with sieved and autoclaved sand. Seedlings were subjected to first CT
      scanning 1 week after seed planting. Our main research objectives concerning root
      systems were: (i) to quantify structural complexity from fractal dimensions
      estimated on skeletal 3-D images built from CT scanning data; (ii) to measure
      growth from volumes and lengths and the derived relative rates and increments,
      after isolating primary and secondary roots from the soil medium in CT scanning
      data; and (iii) to assess differences in complexity and growth per week and over
      Weeks 1-3 for groups of corn plants. Differences between groups were present from
      Week 1; starting in Week 2 secondary roots were present and could be isolated,
      which refined the complexity and growth analyses of root systems. Besides
      expected Week main effects (P < 0.01 or 0.05), Week * Group interaction (P < 0.05
      or 0.10), and Group main effects were observed. Graphical, quantitative, and
      statistical analyses of CT scanning data were thus completed at an unprecedented
      level, and provided new and important insights regarding root system development.
      Repeated CT scanning is the key to a better understanding of the establishment in
      the soil medium of crop plants such as corn and the assessment of salt stress
      effects on developing root systems, in complexity, volume, and length. 

PMID- 25972877
TI  - Effects of environmental factors and management practices on microclimate, winter
      physiology, and frost resistance in trees.
AB  - Freezing stress is one of the most important limiting factors determining the
      ecological distribution and production of tree species. Assessment of frost risk
      is, therefore, critical for forestry, fruit production, and horticulture. Frost
      risk is substantial when hazard (i.e., exposure to damaging freezing
      temperatures) intersects with vulnerability (i.e., frost sensitivity). Based on a
      large number of studies on frost resistance and frost occurrence, we highlight
      the complex interactive roles of environmental conditions, carbohydrates, and
      water status in frost risk development. To supersede the classical empirical
      relations used to model frost hardiness, we propose an integrated
      ecophysiologically-based framework of frost risk assessment. This framework
      details the individual or interactive roles of these factors, and how they are
      distributed in time and space at the individual-tree level (within-crown and
      across organs). Based on this general framework, we are able to highlight factors
      by which different environmental conditions (e.g., temperature, light, flood, and
      drought), and management practices (pruning, thinning, girdling, sheltering,
      water aspersion, irrigation, and fertilization) influence frost sensitivity and
      frost exposure of trees. 

PMID- 25972878
TI  - Partially resistant Cucurbita pepo showed late onset of the Zucchini yellow
      mosaic virus infection due to rapid activation of defense mechanisms as compared
      to susceptible cultivar.
AB  - Zucchini yellow mosaic virus (ZYMV) is an emerging viral pathogen in cucurbit
      growing areas wordwide. Infection causes significant yield losses in several
      species of the family Cucurbitaceae. To identify proteins potentially involved
      with resistance toward infection by the severe ZYMV-H isolate, two Cucurbita pepo
      cultivars (Zelena susceptible and Jaguar partially resistant) were analyzed using
      a two-dimensional gel electrophoresis-based proteomic approach. Initial symptoms
      on leaves (clearing veins) developed 6-7 days post-inoculation (dpi) in the
      susceptible C. pepo cv. Zelena. In contrast, similar symptoms appeared on the
      leaves of partially resistant C. pepo cv. Jaguar only after 15 dpi. This finding
      was confirmed by immune-blot analysis which showed higher levels of viral
      proteins at 6 dpi in the susceptible cultivar. Leaf proteome analyses revealed 28
      and 31 spots differentially abundant between cultivars at 6 and 15 dpi,
      respectively. The variance early in infection can be attributed to a rapid
      activation of proteins involved with redox homeostasis in the partially resistant
      cultivar. Changes in the proteome of the susceptible cultivar are related to the
      cytoskeleton and photosynthesis. 

PMID- 25972880
TI  - X-ray computed tomography uncovers root-root interactions: quantifying spatial
      relationships between interacting root systems in three dimensions.
AB  - Research in the field of plant biology has recently demonstrated that inter- and
      intra-specific interactions belowground can dramatically alter root growth. Our
      aim was to answer questions related to the effect of inter- vs. intra-specific
      interactions on the growth and utilization of undisturbed space by fine roots
      within three dimensions (3D) using micro X-ray computed tomography. To achieve
      this, Populus tremuloides (quaking aspen) and Picea mariana (black spruce)
      seedlings were planted into containers as either solitary individuals, or inter
      /intra-specific pairs, allowed to grow for 2 months, and 3D metrics developed in
      order to quantify their use of belowground space. In both aspen and spruce, inter
      specific root interactions produced a shift in the vertical distribution of the
      root system volume, and deepened the average position of root tips when compared
      to intra-specifically growing seedlings. Inter-specific interactions also
      increased the minimum distance between root tips belonging to the same root
      system. There was no effect of belowground interactions on the radial
      distribution of roots, or the directionality of lateral root growth for either
      species. In conclusion, we found that significant differences were observed more
      often when comparing controls (solitary individuals) and paired seedlings (inter-
      or intra-specific), than when comparing inter- and intra-specifically growing
      seedlings. This would indicate that competition between neighboring seedlings was
      more responsible for shifting fine root growth in both species than was neighbor
      identity. However, significant inter- vs. intra-specific differences were
      observed, which further emphasizes the importance of biological interactions in
      competition studies. 

PMID- 25972879
TI  - Garlic (Allium sativum L.) fertility: transcriptome and proteome analyses provide
      insight into flower and pollen development.
AB  - Commercial cultivars of garlic, a popular condiment, are sterile, making genetic
      studies and breeding of this plant challenging. However, recent fertility
      restoration has enabled advanced physiological and genetic research and
      hybridization in this important crop. Morphophysiological studies, combined with
      transcriptome and proteome analyses and quantitative PCR validation, enabled the
      identification of genes and specific processes involved in gametogenesis in
      fertile and male-sterile garlic genotypes. Both genotypes exhibit normal meiosis
      at early stages of anther development, but in the male-sterile plants, tapetal
      hypertrophy after microspore release leads to pollen degeneration. Transcriptome
      analysis and global gene-expression profiling showed that >16,000 genes are
      differentially expressed in the fertile vs. male-sterile developing flowers.
      Proteome analysis and quantitative comparison of 2D-gel protein maps revealed 36
      significantly different protein spots, 9 of which were present only in the male
      sterile genotype. Bioinformatic and quantitative PCR validation of 10 candidate
      genes exhibited significant expression differences between male-sterile and
      fertile flowers. A comparison of morphophysiological and molecular traits of
      fertile and male-sterile garlic flowers suggests that respiratory restrictions
      and/or non-regulated programmed cell death of the tapetum can lead to energy
      deficiency and consequent pollen abortion. Potential molecular markers for male
      fertility and sterility in garlic are proposed. 

PMID- 25972881
TI  - Optimization of technological procedure for amygdalin isolation from plum seeds
      (Pruni domesticae semen).
AB  - The process of amygdalin extraction from plum seeds was optimized using central
      composite design (CCD) and multilayer perceptron (MLP). The effect of time,
      ethanol concentration, solid-to-liquid ratio, and temperature on the amygdalin
      content in the extracts was estimated using both mathematical models. The MLP 4-3
      1 with exponential function in hidden layer and linear function in output layer
      was used for describing the extraction process. MLP model was more superior
      compared with CCD model due to better prediction ability. According to MLP model,
      the suggested optimal conditions are: time of 120 min, 100% (v/v) ethanol, solid
      to liquid ratio of 1:25 (m/v) and temperature of 34.4 degrees C. The predicted
      value of amygdalin content in the dried extract (25.42 g per 100 g) at these
      conditions was experimentally confirmed (25.30 g per 100 g of dried extract).
      Amygdalin (>90%) was isolated from the complex extraction mixture and
      structurally characterized by FT-IR, UV, and MS methods. 

PMID- 25972883
TI  - Regulation of mRNA translation controls seed germination and is critical for
      seedling vigor.

PMID- 25972882
TI  - The food and environmental safety of Bt crops.
AB  - Bacillus thuringiensis (Bt) microbial pesticides have a 50-year history of safety
      in agriculture. Cry proteins are among the active insecticidal ingredients in
      these pesticides, and genes coding for Cry proteins have been introduced into
      agricultural crops using modern biotechnology. The Cry gene sequences are often
      modified to enable effective expression in planta and several Cry proteins have
      been modified to increase biological activity against the target pest(s).
      Additionally, the domains of different but structurally conserved Cry proteins
      can be combined to produce chimeric proteins with enhanced insecticidal
      properties. Environmental studies are performed and include invertebrates,
      mammals, and avian species. Mammalian studies used to support the food and feed
      safety assessment are also used to support the wild mammal assessment. In
      addition to the NTO assessment, the environmental assessment includes a
      comparative assessment between the Bt crop and the appropriate conventional
      control that is genetically similar but lacks the introduced trait to address
      unintended effects. Specific phenotypic, agronomic, and ecological
      characteristics are measured in the Bt crop and the conventional control to
      evaluate whether the introduction of the insect resistance has resulted in any
      changes that might cause ecological harm in terms of altered weed
      characteristics, susceptibility to pests, or adverse environmental impact.
      Additionally, environmental interaction data are collected in field experiments
      for Bt crop to evaluate potential adverse effects. Further to the agronomic and
      phenotypic evaluation, potential movement of transgenes from a genetically
      modified crop plants into wild relatives is assessed for a new pest resistance
      gene in a new crop. This review summarizes the evidence for safety of crops
      containing Cry proteins for humans, livestock, and other non-target organisms. 

PMID- 25972884
TI  - Stem girdling evidences a trade-off between cambial activity and sprouting and
      dramatically reduces plant transpiration due to feedback inhibition of
      photosynthesis and hormone signaling.
AB  - The photosynthesis source-sink relationship in young Pinus canariensis seedlings
      was modified by stem girdling to investigate sprouting and cambial activity,
      feedback inhibition of photosynthesis, and stem and root hydraulic capacity.
      Removal of bark tissue showed a trade-off between sprouting and diameter growth.
      Above the girdle, growth was accelerated but the number of sprouts was almost
      negligible, whereas below the girdle the response was reversed. Girdling resulted
      in a sharp decrease in whole plant transpiration and root hydraulic conductance.
      The reduction of leaf area after girdling was strengthened by the high levels of
      abscisic acid found in buds which pointed to stronger bud dormancy, preventing a
      new needle flush. Accumulation of sugars in leaves led to a coordinated reduction
      in net photosynthesis (AN) and stomatal conductance (gS) in the short term, but
      later (gS below 0.07 mol m(-2) s(-1)) AN decreased faster. The decrease in
      maximal efficiency of photosystem II (FV/FM) and the operating quantum efficiency
      of photosystem II (PhiPSII) in girdled plants could suggest photoprotection of
      leaves, as shown by the vigorous recovery of AN and PhiPSII after reconnection of
      the phloem. Stem girdling did not affect xylem embolism but increased stem
      hydraulic conductance above the girdle. This study shows that stem girdling
      affects not only the carbon balance, but also the water status of the plant. 

PMID- 25972886
TI  - Polyamine metabolism in flax in response to treatment with pathogenic and non
      pathogenic Fusarium strains.
AB  - Flax crop yield is limited by various environmental stress factors, but the
      largest crop losses worldwide are caused by Fusarium infection. Polyamines are
      one of the many plant metabolites possibly involved in the plant response to
      infection. However, in flax plants the polyamine composition, genes involved in
      polyamine synthesis, and in particular their regulation, were previously unknown.
      The aim of this study was to investigate the polyamine synthesis pathway in flax
      and its involvement in response to pathogen infection. It is well established
      that polyamines are essential for the growth and development of both plants and
      fungi, but their role in pathogen infection still remains unknown. In our study
      we correlated the expression of genes involved in polyamine metabolism with the
      polyamine levels in plant tissues and compared the results for flax seedlings
      treated with two pathogenic and one non-pathogenic strains of Fusarium. We
      observed an increase in the expression of genes participating in polyamine
      synthesis after fungal infection, and it was reflected in an increase of
      polyamine content in the plant tissues. The highest level of mRNA was
      characteristic for ornithine decarboxylase during infection with all tested,
      pathogenic and non-pathogenic, Fusarium strains and the arginine decarboxylase
      gene during infection with the pathogenic strain of Fusarium culmorum. The main
      polyamine identified in the flax seedlings was putrescine, and its level changed
      the most during infection. Moreover, the considerable increase in the contents of
      cell wall-bound polyamines compared to the levels of free and conjugated
      polyamines may indicate that their main role during pathogen infection lies in
      strengthening of the cell wall. In vitro experiments showed that the polyamines
      inhibit Fusarium growth, which suggests that they play an important role in plant
      defense mechanisms. Furthermore, changes in metabolism and content of polyamines
      indicate different defense mechanisms activated in flax in response to infection
      by pathogenic and non-pathogenic Fusarium strains. 

PMID- 25972887
TI  - Chromatin dynamics in pollen mother cells underpin a common scenario at the
      somatic-to-reproductive fate transition of both the male and female lineages in
      Arabidopsis.
AB  - Unlike animals, where the germline is established early during embryogenesis,
      plants set aside their reproductive lineage late in development in dedicated
      floral organs. The specification of pollen mother cells (PMC) committed to
      meiosis takes place in the sporogenous tissue in anther locules and marks the
      somatic-to-reproductive cell fate transition toward the male reproductive
      lineage. Here we show that Arabidopsis PMC differentiation is accompanied by
      large-scale changes in chromatin organization. This is characterized by
      significant increase in nuclear volume, chromatin decondensation, reduction in
      heterochromatin, eviction of linker histones and the H2AZ histone variant. These
      structural alterations are accompanied by dramatic, quantitative changes in
      histone modifications levels compared to that of surrounding somatic cells that
      do not share a sporogenic fate. All these changes are highly reminiscent of those
      we have formerly described in female megaspore mother cells (MMC). This indicates
      that chromatin reprogramming is a common underlying scenario in the somatic-to
      reproductive cell fate transition in both male and female lineages. 

PMID- 25972885
TI  - Integration of P, S, Fe, and Zn nutrition signals in Arabidopsis thaliana:
      potential involvement of PHOSPHATE STARVATION RESPONSE 1 (PHR1).
AB  - Phosphate and sulfate are essential macro-elements for plant growth and
      development, and deficiencies in these mineral elements alter many metabolic
      functions. Nutritional constraints are not restricted to macro-elements.
      Essential metals such as zinc and iron have their homeostasis strictly
      genetically controlled, and deficiency or excess of these micro-elements can
      generate major physiological disorders, also impacting plant growth and
      development. Phosphate and sulfate on one hand, and zinc and iron on the other
      hand, are known to interact. These interactions have been partly described at the
      molecular and physiological levels, and are reviewed here. Furthermore the two
      macro-elements phosphate and sulfate not only interact between themselves but
      also influence zinc and iron nutrition. These intricated nutritional cross-talks
      are presented. The responses of plants to phosphorus, sulfur, zinc, or iron
      deficiencies have been widely studied considering each element separately, and
      some molecular actors of these regulations have been characterized in detail.
      Although some scarce reports have started to examine the interaction of these
      mineral elements two by two, a more complex analysis of the interactions and
      cross-talks between the signaling pathways integrating the homeostasis of these
      various elements is still lacking. However, a MYB-like transcription factor,
      PHOSPHATE STARVATION RESPONSE 1, emerges as a common regulator of phosphate,
      sulfate, zinc, and iron homeostasis, and its role as a potential general
      integrator for the control of mineral nutrition is discussed. 

PMID- 25972888
TI  - Elongator and its epigenetic role in plant development and responses to abiotic
      and biotic stresses.
AB  - Elongator, a six-subunit protein complex, was initially isolated as an interactor
      of hyperphosphorylated RNA polymerase II in yeast, and was subsequently
      identified in animals and plants. Elongator has been implicated in multiple
      cellular activities or biological processes including tRNA modification, histone
      modification, DNA demethylation or methylation, tubulin acetylation, and
      exocytosis. Studies in the model plant Arabidopsis thaliana suggest that the
      structure of Elongator and its functions are highly conserved between plants and
      yeast. Disruption of the Elongator complex in plants leads to aberrant growth and
      development, resistance to abiotic stresses, and susceptibility to plant
      pathogens. The morphological and physiological phenotypes of Arabidopsis
      Elongator mutants are associated with decreased histone acetylation and/or
      altered DNA methylation. This review summarizes recent findings related to the
      epigenetic function of Elongator in plant development and responses to abiotic
      and biotic stresses. 

PMID- 25972889
TI  - Nutrient homeostasis within the plant circadian network.
AB  - Circadian clocks have evolved to enhance adaptive physiology in the predictable,
      fluctuating environment caused by the rotation of the planet. Nutrient
      acquisition is central to plant growth performance and the nutrient demands of a
      plant change according to the time of day. Therefore, major aspects of nutrient
      homeostasis, including carbon assimilation and mineral uptake, are under
      circadian control. It is also emerging that there is feedback of nutritional
      status to the circadian clock to integrate these processes. This review will
      highlight recent insights into the role of the circadian clock in regulating
      plant nutrition as well as discuss the role for nutrients in affecting circadian
      function. 

PMID- 25972890
TI  - Phylogenetic and expression analysis of the NPR1-like gene family from Persea
      americana (Mill.).
AB  - The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) forms an integral part of
      the salicylic acid (SA) pathway in plants and is involved in cross-talk between
      the SA and jasmonic acid/ethylene (JA/ET) pathways. Therefore, NPR1 is essential
      to the effective response of plants to pathogens. Avocado (Persea americana) is a
      commercially important crop worldwide. Significant losses in production result
      from Phytophthora root rot, caused by the hemibiotroph, Phytophthora cinnamomi.
      This oomycete infects the feeder roots of avocado trees leading to an overall
      decline in health and eventual death. The interaction between avocado and P.
      cinnamomi is poorly understood and as such limited control strategies exist. Thus
      uncovering the role of NPR1 in avocado could provide novel insights into the
      avocado - P. cinnamomi interaction. A total of five NPR1-like sequences were
      identified. These sequences were annotated using FGENESH and a maximum-likelihood
      tree was constructed using 34 NPR1-like protein sequences from other plant
      species. The conserved protein domains and functional motifs of these sequences
      were predicted. Reverse transcription quantitative PCR was used to analyze the
      expression of the five NPR1-like sequences in the roots of avocado after
      treatment with salicylic and jasmonic acid, P. cinnamomi infection, across
      different tissues and in P. cinnamomi infected tolerant and susceptible
      rootstocks. Of the five NPR1-like sequences three have strong support for a
      defensive role while two are most likely involved in development. Significant
      differences in the expression profiles of these five NPR1-like genes were
      observed, assisting in functional classification. Understanding the interaction
      of avocado and P. cinnamomi is essential to developing new control strategies.
      This work enables further classification of these genes by means of functional
      annotation and is a crucial step in understanding the role of NPR1 during P.
      cinnamomi infection. 

PMID- 25972891
TI  - R-loops and initiation of DNA replication in human cells: a missing link?
AB  - The unanticipated widespread occurrence of stable hybrid DNA/RNA structures (R
      loops) in human cells and the increasing evidence of their involvement in several
      human malignancies have invigorated the research on R-loop biology in recent
      years. Here we propose that physiological R-loop formation at CpG island
      promoters can contribute to DNA replication origin specification at these
      regions, the most efficient replication initiation sites in mammalian cells.
      Quite likely, this occurs by the strand-displacement reaction activating the
      formation of G-quadruplex structures that target the origin recognition complex
      (ORC) in the single-stranded conformation. In agreement with this, we found that
      R-loops co-localize with the ORC within the same CpG island region in a
      significant fraction of these efficient replication origins, precisely at the
      position displaying the highest density of G4 motifs. This scenario builds on the
      connection between transcription and replication in human cells and suggests that
      R-loop dysregulation at CpG island promoter-origins might contribute to the
      phenotype of DNA replication abnormalities and loss of genome integrity detected
      in cancer cells. 

PMID- 25972893
TI  - The role of long non-coding RNAs in genome formatting and expression.
AB  - Long non-coding RNAs (lncRNAs) are transcripts without protein-coding potential
      but having a pivotal role in numerous biological functions. Long non-coding RNAs
      act as regulators at different levels of gene expression including chromatin
      organization, transcriptional regulation, and post-transcriptional control.
      Misregulation of lncRNAs expression has been found to be associated to cancer and
      other human disorders. Here, we review the different types of lncRNAs, their
      mechanisms of action on genome formatting and expression and emphasized on the
      multifaceted action of the H19 lncRNA. 

PMID- 25972892
TI  - Transcriptional control of stem cell fate by E2Fs and pocket proteins.
AB  - E2F transcription factors and their regulatory partners, the pocket proteins
      (PPs), have emerged as essential regulators of stem cell fate control in a number
      of lineages. In mammals, this role extends from both pluripotent stem cells to
      those encompassing all embryonic germ layers, as well as extra-embryonic
      lineages. E2F/PP-mediated regulation of stem cell decisions is highly
      evolutionarily conserved, and is likely a pivotal biological mechanism underlying
      stem cell homeostasis. This has immense implications for organismal development,
      tissue maintenance, and regeneration. In this article, we discuss the roles of
      E2F factors and PPs in stem cell populations, focusing on mammalian systems. We
      discuss emerging findings that position the E2F and PP families as widespread and
      dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on
      the ever expanding landscape of E2F/PP target genes, and explore the possibility
      that E2Fs are not simply regulators of general 'multi-purpose' cell fate genes
      but can execute tissue- and cell type-specific gene regulatory programs. 

PMID- 25972895
TI  - Identifying differential transcription factor binding in ChIP-seq.
AB  - ChIP seq is a widely used assay to measure genome-wide protein binding. The
      decrease in costs associated with sequencing has led to a rise in the number of
      studies that investigate protein binding across treatment conditions or cell
      lines. In addition to the identification of binding sites, new studies evaluate
      the variation in protein binding between conditions. A number of approaches to
      study differential transcription factor binding have recently been developed.
      Several of these methods build upon established methods from RNA-seq to quantify
      differences in read counts. We compare how these new approaches perform on
      different data sets from the ENCODE project to illustrate the impact of data
      processing pipelines under different study designs. The performance of
      normalization methods for differential ChIP-seq depends strongly on the variation
      in total amount of protein bound between conditions, with total read count
      outperforming effective library size, or variants thereof, when a large variation
      in binding was studied. Use of input subtraction to correct for non-specific
      binding showed a relatively modest impact on the number of differential peaks
      found and the fold change accuracy to biological validation, however a larger
      impact might be expected for samples with more extreme copy number variations
      between them. Still, it did identify a small subset of novel differential regions
      while excluding some differential peaks in regions with high background signal.
      These results highlight proper scaling for between-sample data normalization as
      critical for differential transcription factor binding analysis and suggest
      bioinformaticians need to know about the variation in level of total protein
      binding between conditions to select the best analysis method. At the same time,
      validation using fold-change estimates from qRT-PCR suggests there is still room
      for further method improvement. 

PMID- 25972894
TI  - Replication and transcription on a collision course: eukaryotic regulation
      mechanisms and implications for DNA stability.
AB  - DNA replication and transcription are vital cellular processes during which the
      genetic information is copied into complementary DNA and RNA molecules. Highly
      complex machineries required for DNA and RNA synthesis compete for the same DNA
      template, therefore being on a collision course. Unscheduled replication
      transcription clashes alter the gene transcription program and generate
      replication stress, reducing fork speed. Molecular pathways and mechanisms that
      minimize the conflict between replication and transcription have been extensively
      characterized in prokaryotic cells and recently identified also in eukaryotes. A
      pathological outcome of replication-transcription collisions is the formation of
      stable RNA:DNA hybrids in molecular structures called R-loops. Growing evidence
      suggests that R-loop accumulation promotes both genetic and epigenetic
      instability, thus severely affecting genome functionality. In the present review,
      we summarize the current knowledge related to replication and transcription
      conflicts in eukaryotes, their consequences on genome stability and the pathways
      involved in their resolution. These findings are relevant to clarify the
      molecular basis of cancer and neurodegenerative diseases. 

PMID- 25972896
TI  - Classification of Two Class Motor Imagery Tasks Using Hybrid GA-PSO Based K-Means
      Clustering.
AB  - Transferring the brain computer interface (BCI) from laboratory condition to meet
      the real world application needs BCI to be applied asynchronously without any
      time constraint. High level of dynamism in the electroencephalogram (EEG) signal
      reasons us to look toward evolutionary algorithm (EA). Motivated by these two
      facts, in this work a hybrid GA-PSO based K-means clustering technique has been
      used to distinguish two class motor imagery (MI) tasks. The proposed hybrid GA
      PSO based K-means clustering is found to outperform genetic algorithm (GA) and
      particle swarm optimization (PSO) based K-means clustering techniques in terms of
      both accuracy and execution time. The lesser execution time of hybrid GA-PSO
      technique makes it suitable for real time BCI application. Time frequency
      representation (TFR) techniques have been used to extract the feature of the
      signal under investigation. TFRs based features are extracted and relying on the
      concept of event related synchronization (ERD) and desynchronization (ERD)
      feature vector is formed. 

PMID- 25972897
TI  - Epigenetic-Mediated Downregulation of MU-Protocadherin in Colorectal Tumours.
AB  - Carcinogenesis involves altered cellular interaction and tissue morphology that
      partly arise from aberrant expression of cadherins. Mucin-like protocadherin is
      implicated in intercellular adhesion and its expression was found decreased in
      colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in
      three key types of colorectal tissue samples, for normal mucosa, adenoma, and
      carcinoma. A gradual decrease of mRNA levels and protein expression was observed
      in progressive stages of colorectal carcinogenesis which are consistent with
      reports of increasing MUPCDH 5' promoter region DNA methylation. High MUPCDH
      methylation was also observed in HCT116 and SW480 CRC cell lines that revealed
      low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA
      methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower
      levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as
      well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH
      expression was however restored in HCT116 and SW480 cells in the presence of 5
      Aza-2'-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that MU
      protocadherin downregulation occurs during early stages of tumourigenesis and
      progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are
      involved in this silencing. 

PMID- 25972899
TI  - Selection of Reference Genes for Quantitative Gene Expression in Porcine
      Mesenchymal Stem Cells Derived from Various Sources along with Differentiation
      into Multilineages.
AB  - The identification of stable reference genes is a prerequisite for ensuring
      accurate validation of gene expression, yet too little is known about stable
      reference genes of porcine MSCs. The present study was, therefore, conducted to
      assess the stability of reference genes in porcine MSCs derived from bone marrow
      (BMSCs), adipose (AMSCs), and skin (SMSCs) with their in vitro differentiated
      cells into mesenchymal lineages such as adipocytes, osteocytes, and chondrocytes.
      Twelve commonly used reference genes were investigated for their threshold cycle
      (Ct) values by qRT-PCR. The Ct values of candidate reference genes were analyzed
      by geNorm software to clarify stable expression regardless of experimental
      conditions. Thus, Pearson's correlation was applied to determine correlation
      between the three most stable reference genes (NF3) and optimal number of
      reference genes (NFopt). In assessment of stability of reference gene across
      experimental conditions by geNorm analysis, undifferentiated MSCs and each
      differentiated status into mesenchymal lineages showed slightly different results
      but similar patterns about more or less stable rankings. Furthermore, Pearson's
      correlation revealed high correlation (r > 0.9) between NF3 and NFopt. Overall,
      the present study showed that HMBS, YWHAZ, SDHA, and TBP are suitable reference
      genes for qRT-PCR in porcine MSCs. 

PMID- 25972898
TI  - Application of metabolomics in thyroid cancer research.
AB  - Thyroid cancer is the most common endocrine malignancy with four major types
      distinguished on the basis of histopathological features: papillary, follicular,
      medullary, and anaplastic. Classification of thyroid cancer is the primary step
      in the assessment of prognosis and selection of the treatment. However, in some
      cases, cytological and histological patterns are inconclusive; hence,
      classification based on histopathology could be supported by molecular
      biomarkers, including markers identified with the use of high-throughput "omics"
      techniques. Beside genomics, transcriptomics, and proteomics, metabolomic
      approach emerges as the most downstream attitude reflecting phenotypic changes
      and alterations in pathophysiological states of biological systems. Metabolomics
      using mass spectrometry and magnetic resonance spectroscopy techniques allows
      qualitative and quantitative profiling of small molecules present in biological
      systems. This approach can be applied to reveal metabolic differences between
      different types of thyroid cancer and to identify new potential candidates for
      molecular biomarkers. In this review, we consider current results concerning
      application of metabolomics in the field of thyroid cancer research. Recent
      studies show that metabolomics can provide significant information about the
      discrimination between different types of thyroid lesions. In the near future,
      one could expect a further progress in thyroid cancer metabolomics leading to
      development of molecular markers and improvement of the tumor types
      classification and diagnosis. 

PMID- 25972900
TI  - Correlation between Saliva and Plasma Levels of Endothelin Isoforms ET-1, ET-2,
      and ET-3.
AB  - Although saliva endothelins are emerging as valuable noninvasive cardiovascular
      biomarkers, reports on the relationship between isoforms in saliva and plasma
      remain scarce. We measured endothelins in concurrent saliva and plasma samples (n
      = 30 males; age 18-63) by HPLC-fluorescence. Results revealed statistically
      significant positive correlations among all isoforms between saliva and plasma:
      big endothelin-1 (BET-1, 0.55 +/- 0.27 versus 3.35 +/- 1.28 pmol/mL; r = 0.38, p
      = 0.041), endothelin-1 (ET-1, 0.52 +/- 0.21 versus 3.45 +/- 1.28 pmol/mL; r =
      0.53, p = 0.003), endothelin-2 (ET-2, 0.21 +/- 0.07 versus 1.63 +/- 0.66 pmol/mL;
      r = 0.51, p = 0.004), and endothelin-3 (ET-3, 0.39 +/- 0.19 versus 2.32 +/- 1.44
      pmol/mL; r = 0.75, p < 0.001). Correlations of BET-1, ET-1, and ET-3 within each
      compartment were positive in both plasma (p < 0.05) and saliva (p <= 0.1),
      whereas ET-2 was not significantly correlated with other isoforms in either
      plasma or saliva. For all isoforms, concentrations varied on average fivefold
      between individuals (90th/10th percentiles); individuals with high plasma
      endothelin levels generally had high saliva endothelin levels. Our results reveal
      that salivary ET isoform profiles portray the plasmatic profiles and support the
      view of coordinated regulation of ET-1 and ET-3, but distinct regulatory pathways
      for ET-2. 

PMID- 25972901
TI  - Patterns of thyroid hormone levels in pediatric medullary thyroid carcinoma
      patients on vandetanib therapy.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been associated with elevated
      TSH as a drug class effect. Prior studies of vandetanib in adults with medullary
      thyroid carcinoma (MTC) described an increase in levothyroxine (LT) requirement.
      We studied TSH, free T4, and LT dosing in children and adolescents enrolled in
      the phase I/II trial of vandetanib for medullary thyroid cancer (MTC). METHODS:
      Data from 13 patients with multiple endocrine neoplasia type 2B (MEN 2B) and MTC
      were analyzed [6 M, 7 F, median age 13.0 y (9.1-17.3)] Eleven patients (85%) had
      undergone prior thyroidectomy and all received single-drug therapy with
      vandetanib for > 6 months. Confirmed compliance with vandetanib (67-150
      mg/m(2)/day) and LT was a necessary inclusion criterion. RESULTS: While on
      vandetanib treatment, all 11 athyerotic patients exhibited significantly
      increased TSH levels. The baseline TSH level was 4.37 mclU/ml (0.08 - 23.30); in
      comparison, the first peak TSH concentration on vandetanib was 15.70 mclU/ml
      (12.50 - 137.00, p = 0.0010). The median time to reach the initial peak of
      elevated TSH was 1.8 months (0.3 - 9.3). Free T4 levels remained within the
      normal reference range. An increase from a baseline LT dose of 91 mcg/m(2)/day
      (+/-24) to 116 mcg/m(2)/day (+/-24) was required in order to resume normative TSH
      levels (p = 0.00005), equal to an increase of 36.6% (+/-16.56) in the dosage of
      LT in mcg/day. For the 2 patients with intact thyroid glands, free T4 and TSH
      remained normal over a combined 6 patient years of follow up. CONCLUSIONS: In our
      cohort of pediatric MTC patients, athyreotic patients with preexisting
      hypothyroidism developed increased TSH and reduced free T4 during the first few
      months of treatment with vandetanib, necessitating an increase in LT dosage.
      Additional patients with normal thyroid function before treatment and intact
      glands (n = 2) maintained normal thyroid function tests during treatment.
      Elevated TSH in athyreotic patients may be due to an indirect effect of
      vandetanib on the metabolism of thyroid hormone, or to altered TSH sensitivity at
      the pituitary. Proper recognition and management of abnormal thyroid hormone
      levels is critical in growing children on TKIs. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT00514046.

PMID- 25972902
TI  - A randomized pilot trial of growth hormone with anastrozole versus growth hormone
      alone, starting at the very end of puberty in adolescents with idiopathic short
      stature.
AB  - BACKGROUND: When given during the course of puberty, anastrozole (A), an
      aromatase inhibitor, has been shown to increase the predicted adult height (PAH)
      of GH-deficient (GHD) boys treated with recombinant human growth hormone (rhGH).
      Our study questioned whether this treatment could retain some of its effects in
      non-GHD adolescent boys if started only at the very end of puberty, a time when
      rhGH treatment is denied to short adolescents who have almost reached their final
      height. OBJECTIVE: To explore the effect on adult height of a combination of rhGH
      and A, compared with rhGH alone, at the end of puberty in boys with idiopatic
      short stature (ISS). METHODS: A prospective randomized study comparing rhGH + A
      and rhGH was conducted in 24 healthy adolescent boys aged 15.2 +/- 1.2 yrs with
      serum testosterone at adult levels and a faltering growth velocity <3.5 cm/yr
      leading to a predicted adult height (PAH) <2.5 SDS. Treatments were stopped when
      growth velocity became <10 mm in 6 months or when height was close to 170 cm. A
      historical group of ISS adolescents (N = 17) matched for puberty and growth was
      used for comparison. RESULTS: IGF1 levels remained within normal limits in all
      treated patients. Mean treatment duration was 19 months in the rhGH + A group and
      11.5 months in the rhGH group (P = 6.10(-4)). Adult height reached 168.4 +/- 2.6
      cm in the rhGH + A group and 164.2 +/- 5.6 cm in the rhGH group (P < 0.02). Adult
      height was 160.1 +/- 2.8 cm in the historical controls. CONCLUSION: A combination
      of rhGH and A, started at the very end of puberty, seems to allow boys with ISS
      to reach a greater adult height than rhGH alone. Larger trials are needed to
      confirm this preliminary observation.

PMID- 25972903
TI  - Distribution and predominance of genotype 3 in hepatitis C virus carriers in the
      province of kahramanmaras, Turkey.
AB  - BACKGROUND: The hepatitis C virus (HCV) has six major genotypes and more than 100
      subtypes, and the determination of the responsible genotype, collection of
      epidemiological data, tailoring antiviral therapy, and prediction of prognosis
      have an important place in disease management. OBJECTIVES: The aim of the present
      study was to determine the distribution of HCV genotypes across geographic
      regions and compare these data with those obtained from other geographic
      locations. PATIENTS AND METHODS: The HCV genotypes were identified in HCV RNA
      positive blood samples, obtained from different centers. The HCV genotype was
      determined using molecular methods [Real-Time Polymerase Chain Reaction (RT-PCR)]
      in 313 patients, who were found to be positive for HCV RNA. The presence of HCV
      RNA was investigated using the RT-PCR method in serum samples delivered to the
      Microbiology Laboratory at Kahramanmaras Necip Fazil City Hospital,
      Kahramanmaras, Turkey, from the centers located in Kahramanmaras City center and
      peripheral districts of the province, between March 2010 and August 2014. The HCV
      genotype analysis was performed in HCV RNA positive samples, using RT-PCR
      reagents kit. Urine samples from the patients were tested for amphetamine with an
      Amphetamines II (AMPS2) kit, cocaine was tested with a Cocaine II (COC2) kit,
      opiates were tested with an Opiates II (OPI2) kit, and cannabinoids were tested
      with a Cannabinoids II (THC2) kit in Roche/Hitachi Cobas c501 device. RESULTS:
      The blood samples collected from 313 patients were included in the study. Of
      these patients, 212 (67.7%) were male and 101 (32.3%) were female. The mean age
      of the patients was 41.29 +/- 20.32 years. In terms of HCV genotype distribution,
      162 patients (51.7%) had genotype 1, 144 patients (46%) had genotype 3, four
      patients (1.3%) had genotype 2, and three patients (1%) had genotype 4. The
      results of urine drug tests were available in only 65 patients (20.2%). Of these,
      61 (93.8%) patients had HCV genotype 3. CONCLUSIONS: In conclusion, the
      prevalence of HCV genotype 1 was 51.7%, which was lower than the rates reported
      in other studies in Turkey, while the prevalence of HCV genotype 3 was 46%, which
      was remarkably higher than the reported Turkish data. In addition, the prevalence
      rate for genotype 3 reported in the present study is the highest that has ever
      been reported in the literature.

PMID- 25972904
TI  - The impact of fragility fractures on health-related quality of life in patients
      with primary sclerosing cholangitis.
AB  - BACKGROUND: Osteoporosis occurs frequently in patients with chronic cholestatic
      liver diseases, yet data are scarce regarding the prevalence of osteoporosis and
      fragility fractures and their impact on Health-Related Quality of Life (HRQoL) in
      Primary Sclerosing Cholangitis (PSC). OBJECTIVES: We aimed to assess Bone Mineral
      Density (BMD), physical activity and incidence of fragility fractures in patients
      with PSC. We also sought associations between prior fractures and HRQoL. PATIENTS
      AND METHODS: The study was performed on 33 patients (11 females, 22 males) aged
      35.3 +/- 13 years. HRQoL was assessed by Short Form (SF)-36, Primary Biliary
      Cirrhosis (PBC)-40 and PBC-27 questionnaires. BMD was measured by densitometry in
      the lumbar spine and hip. Physical activity was assessed by questionnaire.
      RESULTS: In 32% of patients, BMD measured in the hip or spine was below 1.0
      Standard Deviation. A history of fragility fractures (distal forearm and ribs)
      was reported in six patients (18%). In SF-36 assessment, patients with fractures
      had lower scores in the role functioning, general health and vitality domains and
      Physical Component Summary (PCS) than those without fractures. Prior fractures
      adjusted for gender and PSC duration were associated with lower PCS and Mental
      Component Summary (MCS) scores. Symptoms and fatigue (assessed by PBC) and prior
      fractures were inversely associated with MCS (P = 0.007). CONCLUSIONS: In middle
      aged subjects with PSC, we found a high rate of non-vertebral fractures and a
      moderately decreased BMD in lumbar spine and hip. Fragility fractures had an
      impact on physical and mental aspects of HRQoL.

PMID- 25972905
TI  - Review of the experiences from the first childhood influenza vaccination
      programme with a live attenuated influenza vaccine in England and Scotland.
AB  - In 2012, the Joint Committee on Vaccination and Immunisation recommended that the
      National Immunisation Programme for influenza be extended to include healthy
      children/adolescents aged 2-17 years. In the UK, extension of this new
      immunisation programme began in 2013-2014 and targeted children aged 2 years and
      3 years in primary care. Several implementation pilots were undertaken in primary
      schools across England, Scotland, Wales and Northern Ireland, as well as a single
      pilot in a secondary school in England. This article shares lessons learnt from
      experiences in England and Scotland to provide guidance for other countries
      considering the addition of childhood influenza vaccination into their national
      immunisation programmes. Recommendations are provided to help ensure effective
      preparation and management of new childhood influenza vaccination programmes in
      other countries. This article describes the processes utilised in England and
      Scotland for programme setup, workforce management, identification and care of
      contraindicated patients, collection of data on vaccine uptake, communication
      strategies, and education of parents and children. 

PMID- 25972906
TI  - Characteristics Associated with Utilization of Asthma-Related Traditional Chinese
      Medicine Services among Asthma Children in Taiwan: A Nationwide Cohort Study.
AB  - Introduction. Previous studies have demonstrated the advantages of TCM use among
      asthmatic children. However, there is a paucity of epidemiologic reports on
      features of TCM users among asthmatic children. This cohort study aimed to
      investigate child's, parent's, and provider's characteristics associated with the
      use of asthma-related TCM services among newly diagnosed asthmatic children.
      Materials and Methods. A nationally representative cohort of one million National
      Health Insurance beneficiaries was used. The newly diagnosed asthma children who
      received asthma medication from western medicine providers from 2005 to 2010 were
      selected as our sample for analysis. Generalized estimating equation was applied
      to identify the child's, parents', and provider's characteristics associated with
      the use of asthma-related TCM among the newly diagnosed asthmatic children.
      Results. Of 20,080 children who were enrolled and followed up for one year, 4,034
      children used TCM for asthma-related treatment. Children with prior experience of
      TCM, pre-school and school aged children, boys, those with more severe asthma or
      poorer health, with higher income parents were more likely to use asthma-related
      TCM. Herbal medicine was the most common modality among asthmatic children.
      Conclusions. There were only 20% newly diagnosed asthmatic children using TCM.
      The findings may shed light on possible integration of TCM with western medicine
      services. 

PMID- 25972908
TI  - Noninvasive carcinoma ex pleomorphic adenoma of the parotid gland: A difficult
      diagnosis on fine needle aspiration.
AB  - Carcinoma ex pleomorphic adenoma (CXPA) is a rare epithelial malignancy that
      arises from a primary or recurrent pleomorphic adenoma (PA). It may be
      noninvasive (NI) or invasive. NI CXPA is extremely rare. Preoperative diagnosis
      on fine needle aspiration (FNA) of CXPA may be difficult and poses a diagnostic
      challenge to clinicians and pathologists. Herein, we describe the FNA findings of
      a case of NI-CXPA. A 69-year-old woman presented with rapid enlargement of a
      stable parotid mass of 25 years. Cytologically, malignant cells were focally
      associated with metachromatic fibromyxoid matrix that was homogeneous and dense
      with a vague fibrillary quality. There were cell groups, papillary-like clusters
      and single malignant cells. The nuclei were pleomorphic with irregularly
      dispersed chromatin, and the cytoplasm was ill-defined and granular. Nucleoli
      were small to inconspicuous. Mitoses and necrosis were not seen. Cytological
      features were not specific for any type of salivary gland carcinoma. The FNA
      diagnosis was primary high-grade adenocarcinoma of the parotid gland, not
      otherwise specified. Facial nerve-sparing total parotidectomy was performed,
      which histologically showed PA interspersed with ducts and nests composed of
      pleomorphic atypical nuclei surrounded by extensive hyalinization. Single cells
      were also noted. No capsular infiltration was seen in the entirely sampled tumor.
      Immunohistochemistry for Ki-67 showed a higher proliferation rate in the
      malignant ducts and p63 positive cells focally surrounded some of the malignant
      ducts. Histological diagnosis was NI-CXPA. Accurate diagnosis is important for
      proper surgical management; however, the preoperative diagnosis of NI-CXPA is
      difficult to make on FNA. 

PMID- 25972907
TI  - Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor
      Function for a Botanical-Derived Drug, PG2.
AB  - PG2 is a botanical drug that is mostly composed of Astragalus polysaccharides
      (APS). Its role in hematopoiesis and relieving cancer-related fatigue has
      recently been clinically investigated in cancer patients. However, systematic
      analyses of its functions are still limited. The aim of this study was to use
      microarray-based expression profiling to evaluate the quality and consistency of
      PG2 from three different product batches and to study biological mechanisms of
      PG2. An integrative molecular analysis approach has been designed to examine
      significant PG2-induced signatures in HL-60 leukemia cells. A quantitative
      analysis of gene expression signatures was conducted for PG2 by hierarchical
      clustering of correlation coefficients. The results showed that PG2 product
      batches were consistent and of high quality. These batches were also functionally
      equivalent to each other with regard to how they modulated the immune and
      hematopoietic systems. Within the PG2 signature, there were five genes associated
      with doxorubicin: IL-8, MDM4, BCL2, PRODH2, and BIRC5. Moreover, the combination
      of PG2 and doxorubicin had a synergistic effect on induced cell death in HL-60
      cells. Together with the bioinformatics-based approach, gene expression profiling
      provided a quantitative measurement for the quality and consistency of herbal
      medicines and revealed new roles (e.g., immune modulation) for PG2 in cancer
      treatment. 

PMID- 25972909
TI  - Cytological variations and typical diagnostic features of endocervical
      adenocarcinoma in situ: A retrospective study of 74 cases.
AB  - BACKGROUND: The sensitivity of Papanicolaou smears for detecting endocervical
      adenocarcinoma in situ (AIS) is very low. A comprehensive cytological analysis of
      endocervical AIS is necessary to increase diagnostic accuracy. METHODS: The
      subjects were 74 patients with pathologically-diagnosed AIS. A total of 140
      Papanicolaou smears were reviewed to calculate the sensitivity of the
      Papanicolaou smears for detecting AIS and the incidence of
      sampling/screening/diagnostic errors. The cytological review was performed by 6
      cytotechnologists, and the final cytological diagnosis was obtained at the
      consensus meeting. We classified the cases into three differentiation types;
      typical type (well-differentiated AIS), polymorphic type (poorly differentiated
      AIS), and mixed typical and polymorphic type. Three cytological subtypes
      (endocervical, endometrioid and intestinal subtypes) of AIS were also analyzed.
      RESULTS: The sensitivity of the original Papanicolaou smears for the detection of
      AIS was 44.6%, while that for the detection of AIS and adenocarcinoma was 63.5%.
      The diagnostic accuracy of AIS increased to 78.5% in the final diagnosis. The
      common characteristic features were microbiopsies/hyperchromatic crowded groups
      (HCG) (82.0%) and mitotic figures (72.2%). The appearance of single cells (2.8%)
      was rare, and all the cervical cytology smears showed no evidence of necrotic
      tumor diathesis. The most common AIS was the typical type (41 cases, 67.2%) among
      all cytologically-diagnosed AIS or adenocarcinoma cases (61 cases). Although
      mixed typical and polymorphic AIS existed in 17 cases (27.9%), pure polymorphic
      AIS was very rare (3 cases, 4.9%). The endocervical subtype was the most
      predominant subtype (67.2%), followed by a few mixed subtypes. The important
      diagnostic keys for AIS cytology are as follows: (1) The appearance of
      microbiopsies/HCG (single-cell pattern is rare), (2) mitotic figures in the
      microbiopsies/HCG, (3) a lack of necrotic tumor diathesis in cases with
      polymorphic AIS, and (4) recognition of typical cytological subtypes.
      CONCLUSIONS: The relatively low diagnostic accuracy AIS was caused by the
      underestimation of microbiopsies/HCG and the overestimation of polymorphic
      components. The typical cytological features of AIS are the presence of
      microbiopsies/HCG with mitotic figures in the absence of necrotic tumor diathesis
      in specimens containing endocervical samples. The recognition of infrequent AIS
      subtypes (endometrioid and intestinal subtypes) is also important.

PMID- 25972910
TI  - Is uncertainty in complex disease epidemiology resolvable?
AB  - The imposed limitations on what we can know about nature have been long
      recognized. Yet in the field of epidemiology a futile search for lifestyle
      related risk factors for common chronic diseases continues unabated. This has led
      to the production of a growing body of evidence about potential lifestyle risk
      factors that tend to be marginal, contradictory, irreproducible, or hard to
      interpret. While epidemiologists are calling for a more refined methodology, I
      argue that our limitation in studying complex diseases is insurmountable. This is
      because the study of lifestyle-related small risks requires accurate measurement
      of multiple behaviors-exposures over a long period of time. It is also because in
      complex systems such as population's health, the effect of rich interactions
      between its parts cannot be predicted based on traditional causal models of
      epidemiology. Within complex systems, understanding the interactions between
      system components can be more important than the contribution of each to disease
      risk. 

PMID- 25972912
TI  - How self-enhancers adapt well to loss: The mediational role of loneliness and
      social functioning.
AB  - OBJECTIVE: The tendency toward unrealistically optimistic self-serving biases,
      known as trait self-enhancement, has been associated with both adaptive benefits
      and negative social consequences. This study explored these potential benefits
      and costs in the context of conjugal bereavement. METHOD: The study included 94
      individuals who had experienced the death of a spouse 1.5-3.0 years prior. The
      sample (62 female, 32 male) ranged in age from 37 to 60 (M = 51.45, SD = 6.08).
      To examine benefits, we used relatively objective measures of overall adjustment:
      structured clinical interviews and ratings from participants' close friends and
      relatives. To examine social adjustment, we examined friends'/relatives' ratings
      of the quality of social interactions and the possible mediating roles of
      perceived loneliness and friend/relative ratings. RESULTS: Trait self-enhancement
      was uniformly associated with positive adjustment: relatively lower symptom
      totals, and friend/relative ratings of both overall better adjustment and better
      social adjustment. Self-enhancers' low loneliness was found to mediate reduced
      symptoms. Also, friends'/relatives' ratings of social functioning appeared to
      mediate self-enhancers' reduced loneliness. CONCLUSIONS: These findings provide
      further empirical data to challenge the longstanding assumption that inaccurate
      self-perception is inherently maladaptive. Authentic benefits may result from
      mistaken perceptions of oneself by influencing the experience of loneliness and
      how one is seen by close friends/relatives. Self-enhancement may be an adaptation
      that provides clinically relevant advantages.

PMID- 25972911
TI  - Pros and cons of CLA consumption: an insight from clinical evidences.
AB  - This comprehensive review critically evaluates whether supposed health benefits
      propounded upon human consumption of conjugated linoleic acids (CLAs) are
      clinically proven or not. With a general introduction on the chemistry of CLA,
      major clinical evidences pertaining to intervention strategies, body composition,
      cardio-vascular health, immunity, asthma, cancer and diabetes are evaluated.
      Supposed adverse effects such as oxidative stress, insulin resistance, irritation
      of intestinal tract and milk fat depression are also examined. It seems that no
      consistent result was observed even in similar studies conducted at different
      laboratories, this may be due to variations in age, gender, racial and
      geographical disparities, coupled with type and dose of CLA supplemented. Thus,
      supposed promising results reported in mechanistic and pre-clinical studies
      cannot be extrapolated with humans, mainly due to the lack of inconsistency in
      analyses, prolonged intervention studies, follow-up studies and international co
      ordination of concerted studies. Briefly, clinical evidences accumulated thus far
      show that CLA is not eliciting significantly promising and consistent health
      effects so as to uphold it as neither a functional nor a medical food. 

PMID- 25972913
TI  - Prediction of high-risk types of human papillomaviruses using statistical model
      of protein "sequence space".
AB  - Discrimination of high-risk types of human papillomaviruses plays an important
      role in the diagnosis and remedy of cervical cancer. Recently, several
      computational methods have been proposed based on protein sequence-based and
      structure-based information, but the information of their related proteins has
      not been used until now. In this paper, we proposed using protein "sequence
      space" to explore this information and used it to predict high-risk types of
      HPVs. The proposed method was tested on 68 samples with known HPV types and 4
      samples without HPV types and further compared with the available approaches. The
      results show that the proposed method achieved the best performance among all the
      evaluated methods with accuracy 95.59% and F1-score 90.91%, which indicates that
      protein "sequence space" could potentially be used to improve prediction of high
      risk types of HPVs. 

PMID- 25972915
TI  - The risk factors of concomitant intraperitoneal and retroperitoneal hemorrhage in
      the patients with blunt abdominal trauma.
AB  - INTRODUCTION: Intraperitoneal and retroperitoneal hemorrhages may occur
      simultaneously in blunt abdominal trauma (BAT) patients. These patients undergo
      emergency laparotomies because of concomitant unstable hemodynamics and positive
      sonographic examination results. However, if the associated retroperitoneal
      hemorrhage is found intraoperatively and cannot be controlled surgically, then
      the patients require post-laparotomy transcatheter arterial embolization (TAE).
      In the current study, we attempted to determine the risk factors for post
      laparotomy TAE. MATERIALS AND METHODS: Patients with concomitant BAT and unstable
      hemodynamic were retrospectively analyzed. The characteristics of the patients
      who underwent laparotomy or who required post-laparotomy TAE were investigated
      and compared. The Tile classification system was used to evaluate the pelvic
      fracture patterns. RESULTS: Seventy-four patients were enrolled in the study.
      Fifty-nine (79.7%) patients underwent laparotomy to treat intra-abdominal
      hemorrhage, and fifteen (20.3%) patients underwent additional post-laparotomy TAE
      because of concomitant retroperitoneal hemorrhage. Pelvic fracture was present in
      80.0% of the post-laparotomy TAE patients. This percentage was significantly
      greater than that of the laparotomy only patients (80.0% vs. 30.5%, p < 0.001).
      Furthermore, 30 patients (40.5%, 30/74) had concomitant pelvic fracture
      diagnoses. Of these patients, eighteen (60%, 18/30) underwent laparotomy only,
      while the other twelve patients (40%, 12/30) required post-laparotomy TAE.
      Compared with the patients who underwent laparotomy only, more patients with Tile
      B1-type pelvic fractures (58.3% vs. 11.1%, p = 0.013) required post-laparotomy
      TAE. CONCLUSION: Regarding BAT patient management, the likelihood of post
      laparotomy TAE should be considered in patients with concomitant pelvic
      fractures. Furthermore, more attention should be directed toward patients with
      Tile B1-type pelvic fractures because of the specific fracture pattern and
      impaction force.

PMID- 25972916
TI  - Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in
      a Spanish multicentric case-control study.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-related malignancies harbour distinct
      serological responses to EBV antigens. We hypothesized that EBV serological
      patterns can be useful to identify different stages of chronic lymphocytic
      leukemia. METHODS: Information on 150 cases with chronic lymphocytic leukemia and
      157 frequency-matched (by age, sex and region) population-based controls from a
      Spanish multicentre case-control study was obtained. EBV immunoglobulin G
      serostatus was evaluated through a peptide-based ELISA and further by immunoblot
      analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40
      and Zebra. Two independent individuals categorized the serological patterns of
      the western blot analysis. Patients with very high response and diversity in EBV
      specific polypeptides, in particular with clear responses to EA-associated
      proteins, were categorized as having an abnormal reactive pattern (ab_EBV).
      Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using
      logistic regression models. RESULTS: Almost all subjects were EBV-IgG positive
      (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of
      cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P =
      0.006), particularly in intermediate/high risk patients. Although based on small
      numbers, the association was modified by smoking with a gradual reduction of
      ab_EBV-related OR for all Rai stages from never smokers to current smokers.
      CONCLUSIONS: Highly distinct EBV antibody diversity patterns revealed by
      immunoblot analysis were detected in cases compared to controls, detectable at
      very early stages of the disease and particularly among non smokers. This study
      provides further evidence of an abnormal immunological response against EBV in
      patients with chronic lymphocytic leukemia.

PMID- 25972914
TI  - A proposal for a CT driven classification of left colon acute diverticulitis.
AB  - Computed tomography (CT) imaging is the most appropriate diagnostic tool to
      confirm suspected left colonic diverticulitis. However, the utility of CT imaging
      goes beyond accurate diagnosis of diverticulitis; the grade of severity on CT
      imaging may drive treatment planning of patients presenting with acute
      diverticulitis. The appropriate management of left colon acute diverticulitis
      remains still debated because of the vast spectrum of clinical presentations and
      different approaches to treatment proposed. The authors present a new simple
      classification system based on both CT scan results driving decisions making
      management of acute diverticulitis that may be universally accepted for day to
      day practice. 

PMID- 25972917
TI  - Psychological trauma and help seeking behaviour amongst resettled Iraqi refugees
      in attending English tuition classes in Australia.
AB  - BACKGROUND: To examine levels of psychological distress and help seeking
      behaviour in resettled refugees attending English tuition classes in Australia,
      and their associations with participants' demographic characteristics. METHODS:
      Data was collected by bilingual interviewers between March and November 2013. A
      volunteer sample of attendees of Adult Migrant English Programs (AMEP) in Western
      Sydney were recruited. Participants were two hundred and twenty five Iraqi
      refugees resettled in Western Sydney, who had left Iraq no earlier than 1991,
      were fluent in Arabic and/or English, and were between the ages of 18 and 70. The
      chief outcome measures used were the Kessler Psychological Distress Scale (K-10)
      as well as The Harvard Trauma Questionnaire (HTQ). RESULTS: On the K-10, 39.8% of
      participants had severe psychological distress, 19.4% moderate distress, and
      40.7% had low to mild distress. Ninety-five percent of participants reported
      having experienced one or more potentially traumatic event (PTE) as defined by
      the HTQ prior to leaving Iraq, with a mean of 14.28 events (SD = 8.69). Thirty
      one percent of participants met the threshold (>=2.5) for clinically significant
      PTSD symptomatology, with a significantly higher occurrence among participants
      with lower education attainment (chi (2) (3) = 8.26, p = .04). Of those
      participants with clinically significant PTSD symptomatology according to the
      HTQ, only 32.9% reported ever having ever sought help for a mental health
      problem. CONCLUSIONS: The high level of distress found in this sample, combined
      with low uptake of mental health care, highlights the need for programs targeted
      to promote help-seeking among Iraqi refugees who have resettled in Australia.
      Further, the higher level of PTSD symptomatology found amongst those with lower
      education attainment has mental health promotion and treatment implications.
      Specifically, in designing service and treatment programs, consideration should
      be given to the possible impact excessive levels of psychological distress may
      have on learning in refugees, to ensure that those who have been unable to
      develop proficiency in the English language receive effective care.

PMID- 25972918
TI  - Child and adolescent psychiatry services in Singapore.
AB  - Singapore is a small young city state with a multi-ethnic and multi-cultural
      population. This article reviews the development of the country's child and
      adolescent psychiatry services through the years, in the background of other
      developments within the country's education, social and legal services. Research
      and other available data on the prevalence of psychiatric problems among children
      and adolescents in Singapore are summarized, although there has been no nation
      wide epidemiological study done. One of the most recent developments has been the
      establishment of a community mental health service, which works collaboratively
      with schools and community partners. Some challenges are also discussed
      especially in the area of child and adolescent psychiatry training. Possible
      future directions include providing mental heath care for preschool children as
      well as epidemiological studies to identify disease prevalence and mental health
      needs among children and adolescents in Singapore. 

PMID- 25972920
TI  - Child psychiatry services in Asia: evolving state of affairs?

PMID- 25972919
TI  - Current state and recent developments of child psychiatry in China.
AB  - China has a population of 1.3 billion, of which 238 million are children under
      age 15. The rapid economic development and social reforms that have taken place
      in recent years all had a great influence on child and adolescent mental health.
      Though a nationwide prevalence study for child and adolescent mental disorders in
      China is lacking, several regional studies have shown the prevalence of mental
      disorders in children to be close to the worldwide prevalence of 20%. This
      article reviews the current status of Chinese child psychiatry, the prevalence of
      specific disorders in China and the influence of culture on the diagnosis and
      treatment of child and adolescent mental disorders. Several important social
      issues are also explored in detail, including the one child policy and left
      behind children of migrating workers. Changes in family structures along with the
      growing competitions in life have weakened the traditional social support system.
      As a result childhood behavioral problems, mood disorders in young college
      students, substance abuse and youth suicide are all increasing in China. Many who
      suffer from mental disorders are not adequately cared for because the scarcity of
      qualified service providers and pathways to care. This article also lists some
      challenges and possible solutions, including the multidisciplinary and culture
      sensitive service model for child mental health. Relevant laws, policies and
      regulations are also introduced. 

PMID- 25972921
TI  - Autonomous buckling of micrometer-sized lipid-protein membrane patches
      constructed by Dictyostelium discoideum.
AB  - BACKGROUND: The cytosol of amoeba cells controls the membrane deformation during
      their motion in vivo. To investigate such ability of the cytosol of amoeba cell,
      Dictyostelium discoideum (Dictyostelium), in vitro, we used lipids extracted from
      Dictyostelium and commercially available phospholipids, and prepared substrate
      supported lipid membrane patches on the micrometer scale by spin coating.
      RESULTS: We found that the spin coater holder, which has pores (pore size = 3.1
      mm) of negative pressure to hold the cover glass induced the concave surface of
      the cover glass. The membrane lipid patches were formed at each position in the
      vicinity of the holder pores and their sizes were in the range of 2.7 to 3.2 *
      10(4) MUm(2). After addition of the cytosol extracted from Dictyostelium to the
      lipid membrane patches, through time-lapse observation with a confocal laser
      scanning fluorescence microscope, we observed an autonomous buckling of the
      Dictyostelium lipid patches and localized behaviours of proteins found within.
      CONCLUSION: The current method serves as the novel technique for the preparation
      of film patches in which the positions of patches are controlled by the holder
      pores without fabricating, modifying, and arranging the chemical properties of
      the solution components of lipids. The findings imply that lipid-binding proteins
      in the cytosol were adsorbed and accumulated within the Dictyostelium lipid
      patches, inducing the transformation of the cell-sized patch.

PMID- 25972922
TI  - Anatomic variant of the inferior lateral cutaneous branch of the radial nerve
      during the posterior approach to the humerus: a case report.
AB  - Iatrogenic injury during the posterior approach to the humerus during operative
      fixation is not an uncommon occurrence. A comprehensive understanding of the
      normal anatomy and its variants is of paramount importance in order to avoid such
      injury. Typically, the inferior lateral cutaneous branch of the radial nerve
      originates towards the distal end of the humerus at the inferior portion of the
      spiral groove. Here, we report an important variant of this nerve, which
      originated significantly more proximal than expected, further emphasizing the
      importance of identification, dissection and protection of the radial nerve and
      its major branches. 

PMID- 25972923
TI  - Bacterial contamination of suction catheter tips during aortic valve replacement
      surgery: a prospective observational cohort study.
AB  - BACKGROUND: Bacterial mediastinitis is a severe complication after open heart
      surgery. The infection causes prolonged hospitalization and an increased
      mortality risk. Observations from orthopaedic surgery showed that the suction
      catheter used during surgery is commonly contaminated with bacteria. The aim of
      this study was to describe the prevalence of suction catheter contamination in
      cardiac surgery and to study if suction time influences the contamination risk.
      METHODS: Fifty suction catheter tips were collected during 25 aortic valve
      replacement operations. The suction tip was exchanged once during the operation
      (after aortotomy closure). The tips were subjected to bacterial contamination
      analysis. RESULTS: In 20 of the 25 investigated cases (80%), bacterial
      contamination was detected on one or both tips. The tip used during the beginning
      of the operation showed bacterial contamination in 13/25 cases (52%) and the
      second tip in 12/25 (48%). In 5/25 cases (20%) both tips were contaminated. There
      was no association between bacterial contamination and suction time. Coagulase
      negative staphylococcus was the most commonly detected microorganism.
      CONCLUSIONS: The suction device should be considered as a potential source of
      bacterial contamination in cardiac surgery. The results suggest that the suction
      catheter should be replaced before key moments like valve implantation and
      sternal closure.

PMID- 25972924
TI  - The dangers of hemilithotomy positioning on traction tables: case report of a
      well-leg drop foot after contralateral femoral nailing.
AB  - BACKGROUND: Postoperative contralateral morbidities after fracture fixation
      surgery by hemilithotomy positioning on traction table is uncommon. We'd report a
      case of unexpected common peroneal nerve palsy developed on the contralateral
      side manifesting with drop foot after a common orthopedic femoral nailing. CASE
      REPORT: A 28-year-old female sustained an unusual common peroneal nerve palsy
      manifesting contralateral drop foot after prolonged femoral nailing. Although the
      initial presentations were similar to the notorious well-leg compartment
      syndrome, a benign course with complete recovery in functions was observed 3
      months later. After neurophysiologic exam and review of pertinent literature,
      this iatrogenic and transient dysfunction was delineated to be position-related
      neuropraxia. CONCLUSION: Position adjustment at intervals or complete avoidance
      of prolonged knee hyperflexion is recommended to prevent contralateral common
      peroneal nerve morbidity.

PMID- 25972925
TI  - An unusual course of the vertebral artery posterior to the nerve root in the
      inter-transverse space: a cadaveric study.
AB  - BACKGROUND: The V2 segment of the vertebral artery is very vulnerable to injury
      during cervical spine surgery. The incidence of vertebral artery injury during
      anterior cervical spine procedures is reported to be 0.22-2.77 %. This is
      partially due to its variable course while running in the transverse foramens of
      the cervical vertebrae. CASE PRESENTATION: The course of the vertebral artery in
      the dissected cadaver of a 79 year old female is presented. Dissection of the
      left vertebral artery showed that the 5(th) nerve root passes in front of the
      vertebral artery in the 4(th) intertransverse space. Further exploration showed
      that although vertebral artery at first passed at the back of the nerve root it
      curved downwards again and after passing underneath the 5(th) nerve root entered
      the 4(th) vertebral body. After making a loop in the left half of the vertebrae,
      vertebral artery ran anterior to the nerve root and after entering the 4(th)
      transverse foramen showed up in the 3(rd) intertransverse space. The shortest
      distance of the vertebral artery to the midline at the 4(th) vertebrae level was
      4.78 mm. CONCLUSIONS: To our knowledge this case is the first report of a nerve
      root lying anterior to the vertebral artery in the intertransverse space of the
      cervical spine. Additionally vertebral artery has never been reported to be so
      close to the midline. This report signifies the importance of obtaining MRI or
      contrast enhanced CT scan prior to any cervical spine surgery in the vicinity of
      the vertebral artery including corpectomies and also careful approach to the
      intertransverse space during the operation.

PMID- 25972926
TI  - De novo identification of differentially methylated regions in the human genome.
AB  - BACKGROUND: The identification and characterisation of differentially methylated
      regions (DMRs) between phenotypes in the human genome is of prime interest in
      epigenetics. We present a novel method, DMRcate, that fits replicated methylation
      measurements from the Illumina HM450K BeadChip (or 450K array) spatially across
      the genome using a Gaussian kernel. DMRcate identifies and ranks the most
      differentially methylated regions across the genome based on tunable kernel
      smoothing of the differential methylation (DM) signal. The method is agnostic to
      both genomic annotation and local change in the direction of the DM signal,
      removes the bias incurred from irregularly spaced methylation sites, and assigns
      significance to each DMR called via comparison to a null model. RESULTS: We show
      that, for both simulated and real data, the predictive performance of DMRcate is
      superior to those of Bumphunter and Probe Lasso, and commensurate with that of
      comb-p. For the real data, we validate all array-derived DMRs from the candidate
      methods on a suite of DMRs derived from whole-genome bisulfite sequencing called
      from the same DNA samples, using two separate phenotype comparisons. CONCLUSIONS:
      The agglomeration of genomically localised individual methylation sites into
      discrete DMRs is currently best served by a combination of DM-signal smoothing
      and subsequent threshold specification. The findings also suggest the design of
      the 450K array shows preference for CpG sites that are more likely to be
      differentially methylated, but its overall coverage does not adequately reflect
      the depth and complexity of methylation signatures afforded by sequencing. For
      the convenience of the research community we have created a user-friendly R
      software package called DMRcate, downloadable from Bioconductor and compatible
      with existing preprocessing packages, which allows others to apply the same DMR
      finding method on 450K array data.

PMID- 25972928
TI  - Associations between toe grip strength and hallux valgus, toe curl ability, and
      foot arch height in Japanese adults aged 20 to 79 years: a cross-sectional study.
AB  - BACKGROUND: The associations between toe grip strength (TGS) and foot structure
      are not well known, although foot structure is inferred to affect TGS. This study
      investigated the associations between TGS and hallux valgus angle (HVA), toe curl
      ability, and foot arch height (FAH). METHODS: This study analysed 227, 20 to 79
      year-old, community-dwelling participants. TGS, HVA formed by the first
      metatarsal bone and the proximal phalanx of the hallux, toe curl ability
      (percentage) calculated as (foot length-flexed foot length)/foot length, and FAH
      (percentage) calculated as navicular height/truncated foot length were measured.
      To elucidate associations between TGS and foot structure, a correlation analysis
      and stepwise multivariate linear regression analyses were performed, based on the
      participant's sex. Pearson's correlation coefficients for TGS with age, height,
      weight, HVA, toe curl ability, and FAH were also calculated. In the stepwise,
      multivariate linear regression analyses, the independent variable was TGS and the
      dependent variables were those that significantly correlated with TGS, as shown
      by the Pearson's correlation coefficients. The significance level was set at 5%.
      RESULTS: According to the Pearson's correlation coefficients, in men, TGS was
      significantly correlated with age, height, toe curl ability, and FAH. According
      to the stepwise multiple regression analysis, TGS correlated with age and toe
      curl ability (adjusted R(2)=0.22). In women, TGS was significantly correlated
      with age, height, and toe curl ability (adjusted R(2)=0.40). CONCLUSIONS: TGS was
      associated with toe curl ability in both men and women. However, TGS was not
      associated with HVA and FAH in men or women. The results of this study may lead
      to the development of effective interventions to improve TGS. However, factors
      other than structure of the foot require more detailed investigation to clarify
      the factors contributing to TGS.

PMID- 25972927
TI  - DNase I hypersensitivity analysis of the mouse brain and retina identifies region
      specific regulatory elements.
AB  - BACKGROUND: The brain, spinal cord, and neural retina comprise the central
      nervous system (CNS) of vertebrates. Understanding the regulatory mechanisms that
      underlie the enormous cell-type diversity of the CNS is a significant challenge.
      Whole-genome mapping of DNase I-hypersensitive sites (DHSs) has been used to
      identify cis-regulatory elements in many tissues. We have applied this approach
      to the mouse CNS, including developing and mature neural retina, whole brain, and
      two well-characterized brain regions, the cerebellum and the cerebral cortex.
      RESULTS: For the various regions and developmental stages of the CNS that we
      analyzed, there were approximately the same number of DHSs; however, there were
      many DHSs unique to each CNS region and developmental stage. Many of the DHSs are
      likely to mark enhancers that are specific to the specific CNS region and
      developmental stage. We validated the DNase I mapping approach for identification
      of CNS enhancers using the existing VISTA Browser database and with in vivo and
      in vitro electroporation of the retina. Analysis of transcription factor
      consensus sites within the DHSs shows distinct region-specific profiles of
      transcriptional regulators particular to each region. Clustering developmentally
      dynamic DHSs in the retina revealed enrichment of developmental stage-specific
      transcriptional regulators. Additionally, we found reporter gene activity in the
      retina driven from several previously uncharacterized regulatory elements
      surrounding the neurodevelopmental gene Otx2. Identification of DHSs shared
      between mouse and human showed region-specific differences in the evolution of
      cis-regulatory elements. CONCLUSIONS: Overall, our results demonstrate the
      potential of genome-wide DNase I mapping to cis-regulatory questions regarding
      the regional diversity within the CNS. These data represent an extensive
      catalogue of potential cis-regulatory elements within the CNS that display region
      and temporal specificity, as well as a set of DHSs common to CNS tissues. Further
      examination of evolutionary conservation of DHSs between CNS regions and
      different species may reveal important cis-regulatory elements in the evolution
      of the mammalian CNS.

PMID- 25972929
TI  - Bilirubin is independently associated with oxidized LDL levels in young obese
      patients.
AB  - BACKGROUND: Bilirubin can prevent lipid oxidation in vitro, but the association
      in vivo with oxidized low-density lipoprotein (Ox-LDL) levels has been poorly
      explored. Our aim is to the association of Ox-LDL with total bilirubin (TB)
      levels and with variables related with metabolic syndrome and inflammation, in
      young obese individuals. FINDINGS: 125 obese patients (13.4 years; 53.6% females)
      were studied. TB, lipid profile including Ox-LDL, markers of glucose metabolism,
      and levels of C-reactive protein (CRP) and adiponectin were determined.
      Anthropometric data was also collected. In all patients, Ox-LDL correlated
      positively with BMI, total cholesterol, LDLc, triglycerides (TG), CRP, glucose,
      insulin and HOMAIR; while inversely with TB and HDLc/Total cholesterol ratio (P <
      0.05 for all). In multiple linear regression analysis, LDLc, TG, HDLc and TB
      levels were significantly associated with Ox-LDL (standardized Beta: 0.656,
      0.293, -0.283, -0.164, respectively; P < 0.01 for all). After removing TG and
      HDLc from the analysis, HOMAIR was included in the regression model. In this new
      model, LDLc remained the best predictor of Ox-LDL levels (beta = 0.665, P <
      0.001), followed by TB (beta = -0.202, P = 0.002) and HOMAIR (beta = 0.163, P =
      0.010). CONCLUSIONS: Lower bilirubin levels may contribute to increased LDL
      oxidation in obese children and adolescents, predisposing to increased
      cardiovascular risk.

PMID- 25972930
TI  - Clinical and molecular data from 61 Brazilian cases of Congenital
      Hyperinsulinemic Hypoglycemia.
AB  - OBJECTIVE: To study the clinical and molecular characteristics of a sample of
      Brazilian patients with Congenital Hyperinsulinemic Hypoglycemia (CHH). METHODS:
      Electronic message was sent to members from Endocrinology Department- Brazilian
      Society of Pediatrics requesting clinical data for all cases of CHH. A whole
      blood sample from living patients was requested for DNA extraction followed by a
      search for mutations of the genes ABCC8, KCNJ11, GCK, GLUD1, HADH, SLC16A1 and
      HNF4A. RESULTS: Of the 61 patients evaluated, 36 (59%) were boys, and only 16
      (26%) were born by normal delivery. Gestational age ranged from 32 to 41 weeks
      (mean = 37 weeks and 6 days). Birth weight ranged from 1590 to 5250 g (mean =
      3430 g). Macrossomia occurred in 14 cases (28%). Age at diagnosis ranged from 1
      to 1080 days (mean = 75 days). DNA for molecular analysis was obtained from 53 of
      the 61 patients. Molecular changes in the ABCC8 gene were detected in 15 (28%) of
      these 53 cases, and mutations in the KCNJ11 gene were detected in 6 (11%).
      Mutations in the GLUD1 gene were detected in 9 cases (17%) of the total series.
      Mutations of the GCK gene in heterozygosis were detected in 3 cases. No mutations
      were detected in the sequencing of genes HADH, SLC16A1 and HNF4A. CONCLUSION: The
      present study conducted in Brazil permitted the collaborative compilation of an
      important number of CHH cases and showed that the present clinical and molecular
      data are similar to those of published global series.

PMID- 25972931
TI  - Superficial temporal artery pseudoaneurysm presenting as extradural hematoma: A
      case report and review of literature.
AB  - Superficial temporal artery (STA) pseudoaneurysm after a craniotomy is very rare
      with only nine cases reported in the literature. However, no cases have been
      reported in the literature about this entity presenting as an emergency in the
      form of extradural hematoma (EDH). This case being one of the rare ones and is
      also unique wherein the indication for craniotomy being intracranial tuberculoma
      that is not yet reported in the literature. We report the first case of a
      postcraniotomy STA pseudoaneurysm induced EDH following craniotomy for
      intracranial tuberculoma. 

PMID- 25972932
TI  - What neurosurgeons need to know about dabigatran etexilate
      (pradax((r))/pradaxa((r))/prazaxa((r))).
AB  - Dabigatran etexaliate is a novel oral anticoagulant that directly inhibits
      thrombin. It offers a number of substantial medical benefits over other oral and
      parenteral anticoagulants but its advent raises important neurosurgical
      considerations. Dabigatran has important potential benefits. Unlike warfarin, it
      does not require routine blood tests to monitor its anticoagulative effect and
      there is no need for dose titration. Drug interactions are greatly simplified
      when compared to warfarin as dabigatran is not metabolized by cytochrome p450
      isoenzymes. As a result, dabigatran has been approved in many jurisdictions for
      DVT prophylaxis after orthopaedic surgery and also for the prevention of embolic
      events associated with non-valvular atrial fibrillation. There are, however,
      important neurosurgical challenges associated with regular dabigatran use. Unlike
      current anti-coagulants, there is no specific reversal agent for dabigatran.
      Known reversal options include activated charcoal (within one to two hours of
      intake) and renal dialysis. Protamine sulfate and vitamin K are unlikely to
      affect the activity of dabigatran. Platelet concentrates will not inactivate
      dabigatran's anti-thrombin properties. Assessing the degree of anticoagulation is
      difficult as conventional markers of serum coagulability are typically normal in
      patients taking dabigatran. The potential neurosurgical challenges of dabigatran
      were cast in sharp relief by a recent case report from the United States that is
      considered in this note. In the absence of a clear reversal pathway, we propose a
      treatment algorithm for chronic dabigatran use based on the replacement of any
      deficient factors and rapid access to renal dialysis. 

PMID- 25972933
TI  - Quantitative and qualitative analysis of the working area obtained by endoscope
      and microscope in pterional and orbitozigomatic approach to the basilar artery
      bifurcation using computed tomography based frameless stereotaxy: A cadaver
      study.
AB  - OBJECTIVE: Basilar aneurisms are one of the most complex and challenging
      pathologies for neurosurgeons to treat. Endoscopy is a recently rediscovered
      neurosurgical technique that could lend itself well to overcome some of the
      vascular visualization challenges associated with this pathology. The purpose of
      this study was to quantify and compare the basilar artery (BA) bifurcation (tip
      of the basilar) working area afforded by the microscope and the endoscope using
      different approaches and image guidance. MATERIALS AND METHODS: We performed a
      total of 9 dissections, including pterional (PT) and orbitozygomatic (OZ)
      approaches bilaterally in five whole, fresh cadaver heads. We used computed
      tomography based image guidance for intraoperative navigation as well as for
      quantitative measurements. We estimated the working area of the tip of the
      basilar, using both a rigid endoscope and an operating microscope. Operability
      was qualitatively assessed by the senior authors. RESULTS: In microscopic
      exposure, the OZ approach provided greater working area (160 +/- 34.3 mm(2))
      compared to the PT approach (129.8 +/- 37.6 mm(2)) (P > 0.05). The working area
      in both PT and OZ approaches using 0 degrees  and 30 degrees  endoscopes was
      larger than the one available using the microscope alone (P < 0.05). In the PT
      approach, both 0 degrees  and 30 degrees  endoscopes provided a working area
      greater than a microscopic OZ approach (P < 0.05) and an area comparable to the
      OZ endoscopic approach (P > 0.05). CONCLUSION: Integration of endoscope and
      microscope in both PT and OZ approaches can provide significantly greater
      surgical exposure of the BA bifurcation compared to that afforded by the
      conventional approaches alone.

PMID- 25972934
TI  - A 10-year follow-up of transpedicular screw fixation and intervertebral
      autogenous posterior iliac crest bone graft or intervertebral B-Twin system in
      failed back surgery syndrome.
AB  - BACKGROUND: The spine surgeons have been combining anterior and posterolateral
      fusion (circumferential fusion) as the final solution to treat spinal disorders
      and many have been using it to treat failed back surgery syndrome (FBSS). In
      present study, we analyzed and compared the clinical and radiological outcomes in
      patients with transpedicular screw fixation and intervertebral autogenous
      posterior iliac crest bone graft or in patients with transpedicular screw
      fixation and intervertebral B-Twin system for FBSS with a follow-up period of 10
      years after the surgery. MATERIALS AND METHODS: This study was a retrospective
      case study performed on 55 patients with FBSS. Clinical and radiological changes
      were compared between the two groups of patients on the basis of improvement of
      back pain, radicular pain, and work capacity. Outcome was measured in terms of
      Oswestry Low Back Pain Disability Index, and the changes in pain and function
      were documented every year from before surgery until 2012. We analyzed the
      evolution of 55 cases of FBSS those underwent segmental circumferential posterior
      fusions from June 2001 to February 2003, operated by a single surgeon and
      followed up during 10 years until February 2012. The patients were divided into 2
      groups: In 25 patients, posterolateral fusions with LegacyTM (Medtronic, Inc.
      NYSE: MDT) screws and intersomatic autogenous posterior iliac crest bone graft
      was performed, and, in 30 patients, posterolateral fusions with the same screws
      and intersomatic fusion B-Twin (Biomet Spain Orthopaedics, S.L.) system was
      performed. In all cases, we used posterior lumbar interbody fusion
      (PLIF)/transforaminal lumbar interbody fusion (TLIF) approach for intervertebral
      graft, and the artrodesis was supplemented at intertransverse level with
      Autologus Growth Factor (AGF-MBA INCORPORADO, S.A.). The outcome was measured in
      terms of Oswestry Low Back Pain Disability Index, and the changes in pain and
      function were documented every year and compared from before surgery to the final
      follow-up visit. Preoperative and postoperative scores were available for all
      patients. RESULTS: The average age of these patients was comparable in both
      groups (mean age 42.6 versus 50.2 years). The average follow-up period was 200.6
      months in the first group (screws and intersomatic bone) and 184.4 months in the
      second group (screws and B-Twin). In the autologus bone graft group, the CT scan
      and Rx study revealed loss of height of intervertebral space between 25% and 45%
      of 24 h postoperative height of intervertebral operated disc, and the patients
      continued to lose the height until 20 months after the surgery. In the B Twin
      group, the CT scan and Rx study revealed a loss of height of the intervertebral
      level of 8-12% over a period of 9 months follow-up, followed by stability. A
      total of 31 patients (55%) had improved Oswestry Low Back Pain Disability Index
      >40% of the total possible points, although this did not reflect in PSI or return
      to work rate. CONCLUSIONS: The patients with rigid fixation do well in terms of
      correction of lumbar lordosis, but they do not do well in terms of recurrence of
      pain. Furthermore, they need some kind of intervention to control pain after the
      first year after surgery. In patients in whom bone graft is used, although they
      do not maintain and sustain the lumbar lordosis in the long term, they have less
      recurrence of pain with less chances of intervention for pain control.

PMID- 25972935
TI  - The role of urodynamic studies in the diagnosis and treatment of patients with
      spina bifida.
AB  - AIM: Spina bifida (SB) is a congenital deformity that is frequently seen in
      infancy. Surgical treatment and clinical follow-up of patients with the diagnosis
      of SB are important to provide education to the patients and their relatives, to
      increase patient survival, to ensure that they have a more comfortable life.
      Neuro-urological problems are highly important for the patients in terms of both
      social and medical. MATERIALS AND METHODS: The medical records of patients who
      underwent surgery for SB and tethered cord syndrome at our clinic in the past
      year were retrospectively evaluated. The results of urodynamic studies of the
      patients were evaluated. The results of patients who underwent control urodynamic
      studies during the follow-up period were compared with the previous results, and
      their clinical courses were determined. RESULTS: The most frequent urodynamic
      changes in patients were hyperactive detrusor activity and detrusor sphincter
      dyssynergy preoperatively. CONCLUSION: A significant improvement was observed
      when the results of postoperative urodynamic studies were evaluated in patients
      who underwent surgery for tethered cord.

PMID- 25972936
TI  - Cushing's ulcer: Further reflections.
AB  - BACKGROUND: Brain tumors, traumatic head injury, and other intracranial processes
      including infections, can cause increased intracranial pressure and lead to
      overstimulation of the vagus nerve. As a result, increased secretion of gastric
      acid may occur which leads to gastro-duodenal ulcer formation known as Cushing's
      ulcer. METHODS: A review of original records of Dr. Harvey Cushing's patients
      suffering from gastro-duodenal ulcers was performed followed by a discussion of
      the available literature. We also reviewed the clinical records of the patients
      never reported by Cushing to gain his perspective in describing this phenomenon.
      Dr. Cushing was intrigued to investigate gastro-duodenal ulcers as he lost
      patients to acute gastrointestinal perforations following successful brain tumor
      operations. It is indeed ironic that Harvey Cushing developed a gastro-duodenal
      ulcer in his later years with failing health. RESULTS: Clinically shown by
      Cushing's Yale Registry, a tumor or lesion can disrupt this circuitry, leading to
      gastroduodenal ulceration. Cushing said that it was "reasonable to believe that
      the perforations following posterior fossa cerebellar operations were produced in
      like fashion by an irritative disturbance either of fiber tracts or vagal centers
      in the brain stem." CONCLUSION: Harvey Cushing's pioneering work depicted in his
      Yale registry serves as a milestone for continuing research that can further
      discern this pathway.

PMID- 25972937
TI  - Minimally invasive percutaneous endoscopic 2 levels adjacent lumbar discectomy
      through 1 portal skin incision: Preliminary study.
AB  - BACKGROUND: Acute lumbar disc herniation can occur in every lumbar intervertebral
      disc space and in multiple levels simultaneously. In the cases of 2 levels
      adjacent lumbar disc herniations of severe unilateral radiculopathic leg pain
      caused by compression of the nerve roots, respectively, multiple incision or long
      incision is generally needed for simultaneous removal of disc fragment in 2
      levels. OBJECTIVES: We proposed the minimally invasive one portal skin incision
      endoscopic discectomy is effective and safe method to treat 2 levels adjacent
      lumbar disc herniation. MATERIALS AND METHODS: We have experimented total 8 cases
      of 2 levels adjacent lumbar disc herniation having unilateral radiculopathic pain
      respectively. All cases are 2 levels adjacent lumbar disc herniation. We have
      tried a percutaneous endoscopic transforaminal approach through minimal one
      portal skin incision and remove the two herniated disc materials in the adjacent
      levels. RESULTS: The L2-L3 level was involved in 2 patients, L3-L4 level in 6
      patients, while the L4-L5 level was involved in 7 patients, L5-S1 level in 1
      patient. The mean follow-up was 18.5 months. The mean visual analogue score (VAS)
      of the patients prior to surgery was 7.75, and the mean postoperative VAS was
      2.375. According to Macnab's criteria, 3 patients had excellent results, 4
      patients had good results, 1 patient had fair results, and no patient had a poor
      result; satisfactory results were obtained in 87.5% of the cases. CONCLUSION: The
      percutaneous endoscopic transforaminal approach through 1 skin portal incision
      could be effective surgical method in unilateral adjacent 2 levels lumbar disc
      herniation.

PMID- 25972938
TI  - Solitary dural plasmacytoma with parenchymal invasion.
AB  - Primary solitary dural plasmacytoma is an uncommon neoplasm of plasma cell. The
      clinical presentation and neuroradiological findings of these tumors may be
      deceptive and resemble to the other most prevalent brain tumors. Solitary
      plasmacytoma mostly shows a benign behavior and malignant features like local
      invasion is so rare. We describe the case of parenchymal brain involvement by
      solitary dural plasmacytoma. 

PMID- 25972939
TI  - Langerhans cell histiocytosis in monozygotic twins with central diabetes
      insipidus and hypophyseal masses.
AB  - Langerhans cell histiocytosis (LCH) is a systemic disease mainly affecting
      children and young adults. It can manifest as single system disorder or multi
      system involvement. When the central nervous system is involved, the hypothalamic
      pituitary axis is the most common location affected. Herein we report a rare case
      of Langerhans cell histiocytosis in monozygotic twins both with central diabetes
      and hypophyseal masses. This is the first report about LCH in monozygotic twins
      with hypophyseal lesions. 

PMID- 25972940
TI  - Removal of lumber spine foreign body using minimal access system with navigation.
AB  - Removal of a foreign body from the spine is often time a surgical challenge.
      Recent developments in computer-assisted surgery (CAS) have brought major
      improvements into the operating room. Most Medical procedures nowadays take
      advantage of the minimal invasiveness, precision, velocity and interactivity
      provided by the computer-assisted systems. Minimally invasive techniques (MIT)
      like microscopy, stereotaxy, endoscopy and neuronavigation facilitate the
      procedures improve neurosurgical results and reduce operative complications. In
      this technical report we used minimal access system with navigation to remove a
      broken spinal needle at L4-L5 level from an asymptomatic lady post delivery using
      a custom-made navigation-mounted pituitary rongeur. 

PMID- 25972941
TI  - Intraparenchymal anaplastic meningioma in a child: A rare entity.
AB  - Brain tumors are not rare in children. The common brain tumors in children are
      medulloblastomas and craniopharyngiomas. Intraparenchymal meningiomas are very
      rare. We report a case of intraparenchymal meningioma in a child who was operated
      with a preoperative impression of a primitive neuroectodermal tumor. 

PMID- 25972942
TI  - Vasospasm after intraventricular hemorrhage caused by arteriovenous malformation.
AB  - Intraventricular hemorrhage (IVH) induced vasospasm is rare in clinical practice.
      We report a case with vasospasm 10 days after IVH due to thalamic bleeding from
      an arteriovenous malformation. The vasospasm was so severe that transarterial
      embolization failed. Follow-up angiography could not reveal the vascular lesion
      and spontaneous thrombosis was considered. The discussion includes literature
      review and possible mechanism of such phenomenon. IVH-related vasospasm is rare
      but should always be kept in mind. Early detection with proper treatment provides
      better clinical outcome in such cases. 

PMID- 25972943
TI  - Middle cerebral artery branch occlusion mimicking an aneurysm.

PMID- 25972944
TI  - Partial thickness autologus calvarial bone orbitocranioplasty for a sphenorbital
      encephalocele presenting as pulsatile exophthalmos.
AB  - Basal encephalocele accounts only 1.5% of all encephaloceles. But Sphenorbital
      encephalocele is the rarest cause of herniation of brain into orbit leading to
      pulsatile exphothalmos. Authors presenting a case of sphenorbital encephalocele
      in a 16 yrs old girl successsfully managed by orbitcranioplasty by partilal
      thickness autologus calvarial bone graft. 

PMID- 25972945
TI  - Acute bilateral isolated foot drop: Report of two cases.
AB  - Foot drop is defined as the weakness of the foot and ankle dorsiflexion. Acute
      unilateral foot drop is a well-documented entity, whereas bilateral foot drop is
      rarely documented. Slowly progressing bilateral foot drop may occur with various
      metabolic causes, parasagittal intracranial pathologies, and cauda equina
      syndrome. Acute onset of bilateral foot drop due to disc herniation is extremely
      rare. Here we present two cases of acute bilateral foot drop due to disc
      herniation. The first patient was a 45-year-old man presented with acute
      bilateral foot drop, without any sign of the cauda equina syndrome. Lumbar
      magnetic resonance imaging of the patient revealed L4-5 disc herniation. To our
      knowledge, this is the first presented case of acute bilateral foot drop without
      any signs of cauda equina syndrome caused by L4-5 disc herniation. The second
      patient was a 50-year-old man who was also presented with acute bilateral foot
      drop, and had T12-L1 disc herniation with intradural extension. Also this is the
      first presented case of T12-L1 disc herniation with intradural extension causing
      acute bilateral foot drop. We performed emergent decompressive laminectomy to
      both of the patients and extrude disc materials were excised. Both of the
      patients were recovered with favorable outcome. 

PMID- 25972946
TI  - Thoracic intramedullary schwannoma: A case report and review of literature.
AB  - Intramedullary schwannomas are rare spinal cord tumors. Most of these tumors have
      been reported as a single lesion in the spinal cord. Up until today approximately
      50 cases of intramedullary shwannomas not related to neurofibromatosis have been
      described. We describe a rare case of thoracic intramedullary tumour in a 28 year
      old male patient who presented with progressive weakness of both the lower limbs
      and decreased sensation below D2 dermatomal level. Magnetic resonance imaging
      revealed an intramedullary lesion from D1 toD7. D1 to D7 laminoplasty and near
      total excision of the mass done. Total removal was difficult because of the
      infiltrative nature of the tumour. Histopathological report confirmed the
      diagnosis of the schwannoma. Possible site of origin and pathogenesis of
      intramedullary tumour have been discussed. 

PMID- 25972947
TI  - Subdural actinomycoma presenting as recurrent chronic subdural hematoma.
AB  - Actimomycosis is a rare chronic bacterial infection of the central nervous
      system, and subdural actinomycoma is extremely rare. This case report brings to
      bear an uncommon association between subdural actinomycosis with chronic subdural
      hematoma. Subdural actinomycoma may present as a diagnostic conundrum and could
      be mistaken radiologically for either a subdural hematoma or an empyaema. 

PMID- 25972948
TI  - Multiple spinal and cranial meningiomas: A case report and review of literature.
AB  - Though meningiomas are common neoplasms of the nervous system, the occurrence of
      multiple meningiomas in different neuraxial compartments is rather rare. We
      report a case of a 62-year-old female who presented with spastic paraparesis in
      both lower limbs, and was found to have multiple homogenously enhancing tumors of
      dorsolumbar spine. Cranial magnetic resonance imaging (MRI) revealed multiple
      bilateral supratentorial meningiomas. She underwent multiple level laminectomy
      and total removal of spinal tumors after which power improved in both lower
      limbs. Histopathology revealed psammomatous meningiomas. Only around 19 cases of
      multiple cranial and spinal meningiomas have been reported, of which, only five
      cases have more than one spinal meningioma. The implication of the incidence of
      such multiple meningiomas in the same patient with relevance to investigations
      and decision making are discussed along with a brief review of literature of
      cases with multiple spinal and cranial meningiomas. 

PMID- 25972949
TI  - Malignant fibrous histiocytoma of the skull base: A neurosurgical nuance.
AB  - A 69-year-old male, treated for colonic carcinoma 15 years back, presented to our
      services with status epilepticus. He had complaints of headache and vomiting for
      7 days prior to presentation. Computed tomography and magnetic resonance imaging
      of the brain revealed heterogeneous, lobulated and osteolytic tumor involving
      middle and posterior cranial fossa. Excision of the tumor was planned in two
      stages. Middle fossa component was removed through right temporobasal approach.
      Histopathology was suggestive of malignant fibrous histiocytoma. Patient
      succumbed to pneumonia and septicemia in the postoperative period. Pathology,
      clinical features and therapeutic challenges of this clinical entity have been
      briefly reviewed. 

PMID- 25972950
TI  - Spontaneous atlantoaxial subluxation associated with tonsillitis.
AB  - Atlantoaxial subluxation is a rare condition and requires a high index of
      suspicion to diagnose and treat in order to avoid long-term sequelae. Here, we
      present a case of late presentation of a nontraumatic rotatory subluxation of the
      atlantoaxial joint or atlantoaxial rotatory subluxation. A 17-year-old girl
      presented 3 months after the onset of nonspecific upper limb sensory symptoms
      which eventually settled spontaneously. Initial conservative management by the
      general practitioner had no effect. Computed tomography scanning revealed a Type
      1 dislocation with rotatory fixation and with <3 mm anterior displacement of the
      atlas. The management of Type 1 subluxations is usually conservative with bed
      rest, oral nonsteroidal anti-inflammatory drugs, muscle relaxants, reduction (if
      required) and immobilization with a soft collar. This patient, however, required
      more invasive management due to the late presentation and slightly greater fixed
      deformity. As the subluxation could not be reduced with active manipulation,
      Gardner-Wells tongs with traction were applied. She then progressed to a pinned
      HALO, cyber neck support and subsequently an aspen collar which was eventually
      weaned off over a few weeks. The outcome and radiologic alignment at follow-up
      was satisfactory. 

PMID- 25972951
TI  - Cerebral phaeohyphomycosis: A rare case from central India.
AB  - Cerebral phaeohyphomycosis is a rare and frequently fatal disease, often caused
      by hematogenous spread of pathogens that are inoculated in the skin of the
      extremities following minor trauma, and its mortality rate is much high despite
      aggressive treatment. A rare case of 25-year-old immuno-competent man with
      cerebral abscess has been described. The etiological agent was microbiologically
      proved to be a dematiaceous fungi Cladophilaophora bantiana, which is primarily a
      neurotropic fungus causing deep-seated intra-cranial infections. Treatment was
      individualized by surgical intervention and appropriate anti-fungal therapy.
      Thus, it has been described as a successfully managed case of cerebral
      phaeohyphomycosis known to be associated with a high degree of morbidity and
      mortality. 

PMID- 25972952
TI  - Anaphylactic reaction after autologous blood transfusion: A case report and
      review of the literature.
AB  - Autologous blood transfusion as a cause of intraoperative anaphylaxis is very
      rare. We encountered one such life-threatening event in a 72-year-old patient
      undergoing laminectomy and pedicle screw fixation. The probable cause identified
      was the floseal mixed autologous blood transfusion. Review of literature has been
      done, and measures to avoid such an event in the future are discussed. 

PMID- 25972953
TI  - Life-threatening large subcutaneous hematoma after minor head trauma: A young
      female patient who was suspected of having new Ehlers-Danlos syndrome.
AB  - Life-threatening large subcutaneous hematomas after minor injury are rare
      clinical states for young people; however these patients may have hidden
      diseases, which can cause a tendency to bleed. A 31-year-old woman visited our
      hospital after minor injury. The first computed tomography (CT) scan revealed a
      small subcutaneous hematoma, but her head bulged and the second CT scan revealed
      her subcutaneous hematoma had become enlarged. Two surgeries were needed to stop
      the bleeding and. Though she received intensive care, she died 48 days after
      onset. The new Ehlers-Danlos syndrome (EDS), known as EDS Kosho type (EDSKT), is
      a connective tissue disease, in which patients often experience large
      subcutaneous hematomas. We suspected our patient had EDSKT because her clinical
      features were compatible with this syndrome. Our findings support the notion that
      large subcutaneous hematomas in young patients with connective tissue disease can
      be fatal; a careful follow-up is required. 

PMID- 25972954
TI  - Incidental diagnosis of two intracranial aneurysms following surgical evacuation
      of chronic subdural hematoma.
AB  - The development of subarachnoid hemorrhage (SAH) following evacuation of chronic
      subdural hematoma (CSDH) is a very rare phenomenon. SAH in this context occurring
      secondary to intracranial aneurysm rupture is still rare. We report a case of an
      elderly lady who presented with right hemiplegia and altered sensorium. Computed
      tomography (CT) scan of the brain revealed a left fronto-temporoparietal CSDH
      with midline shift, which was promptly evacuated surgically via a single burr
      hole. Postoperatively, her level of consciousness deteriorated and there was
      increased the amount of drain. Emergency CT of the brain revealed diffuse SAH. CT
      cerebral angiogram revealed one aneurysm each in the right internal carotid
      artery and anterior communicating artery. Meanwhile, her consciousness level
      improved on conservative management. The relatives were not keen for further
      follow-up. 

PMID- 25972955
TI  - Cystic pilomyxoid astrocytoma on suprasellar region in 7-year-old girl: Treatment
      and strategy.
AB  - Pilomyxoid astrocytoma (PMA) is a recently described entity with similar features
      to pilocytic astrocytoma but with a rare occurrence. As a new diagnosis, no
      treatment guideline of PMA has been established; but generally, as for any low
      grade gliomas, radical resection is performed if the location is favorable. In
      this report, we wished to share our experience treating the PMA. The authors
      presented a case of a 7-year-old girl with bitemporal hemianopia. From the
      history, the patient had a 4-month history of headache, following with nausea and
      projectile vomiting 1 week before hospital admission. Past history of seizure,
      weakness of left extremities, and decreased consciousness were reported. Computed
      tomography (CT) scanning showed acute obstructive hydrocephalus and an
      isohypodense mass at suprasellar region with the cystic component. We performed
      ventriculo-peritoneal-shunt to reduce the acute hydrocephalus, followed by
      craniotomy tumor removal 2 weeks later. The patient underwent radiotherapy and
      medical rehabilitation. Diagnosis of PMA was made on the basis of pathologic
      anatomy result, which showed a myxoid background with pseudorosette.
      Postoperative CT showed a residual tumor at right parasellar area without
      hydrocephalus. After the surgery, the treatment was followed with radiotherapy
      for 20 times within 2 months. Postradiation CT performed 1-year later showed a
      significant reduction of the tumor mass. There were no new postoperative
      deficits. The patient had improvement of the visual field and motor strength. The
      authors reported a case of a 7-year-old girl with PMA. Surgical resection
      combined with radiotherapy was performed to control the growth of PMA. More
      observation and further studies are required to refine the treatment methods. 

PMID- 25972956
TI  - Intracranial hypotension after syringopleural shunting in posttraumatic
      syringomyelia: Case report and review of the literature.
AB  - We report a case of a 45-year-old male with a syringopleural shunt who developed
      intracranial hypotension. The patient presented with 2 weeks history of worsening
      headache and back pain, on a background of having had a syringopleural shunt
      inserted for a thoracic posttraumatic syrinx. Computerized tomography imaging of
      the brain revealed bilateral subdural fluid collections. Magnetic resonance
      imaging appearances of spinal and intracranial pachymeningeal enhancement
      confirmed intracranial hypotension. We present a rare case of intracranial
      hypotension secondary to syringopleural shunting in a patient with posttraumatic
      syringomyelia. 

PMID- 25972957
TI  - Pure cortical ependymoma: A rare entity.
AB  - Ependymomas are mostly infratentorial, intraventricular tumor, accounting for 2
      9% of all central nervous system tumors. Supratentorial pure cortical ependymoma
      are extremely rare tumor with definite ependymal morphology and uncertain
      histogenesis. They are mostly low grade tumor and are cured with resection,
      rendering them favorable prognosis. Our case is of 14-year-old female presenting
      with headache and convulsion of short duration. She underwent gross total
      excision of the tumor without radiation therapy and her follow-up is uneventful. 

PMID- 25972958
TI  - Metaplastic conus meningioma and its applied aspects.
AB  - Cranial meningiomas may present with or without major deficits depending on their
      location and morphology. Spinal meningiomas account for 25% of all the spinal
      tumors. Most commonly encountered in the dorsal spine in middle-aged females,
      these intradural-extramedullary tumors can usually be excised without difficulty.
      Rarely, they can be encountered in the lumbar spine and may create many tactical
      problems for the surgical team especially if it is calcified and contains
      metaplastic bone. We report a 55-year-old patient who presented with backache and
      investigations revealed a calcified lesion at L1 level that was thought of as an
      ependymoma initially. Intraoperatively, the lesion was calcified in parts, and
      the histopathology revealed it to be a metaplastic meningioma with calcification.
      The patient had a transient hip weakness, which recovered completely later on.
      Calcification in meningiomas is common. However, frank bony metaplasia is
      extremely rare. More importantly, the applied aspect of their presence in the
      region of conus lies in the careful dissection to prevent damage to the
      surrounding neural structures. Awareness regarding the same may help us
      preventing complications in the future. 

PMID- 25972959
TI  - Rare case report of Traumatic neuroma of anterior superior alveolar nerve
      associated with high frenal attachment.
AB  - We present an incredible case of traumatic neuroma (TN) in the anterior superior
      alveolar nerve leading to the swelling in the upper labial mucosa. This paper
      attempts to highlight the rarity of site of occurrence of this lesion and reports
      the first case of TN of anterior superior alveolar nerve. 

PMID- 25972960
TI  - Rhabdoid meningioma lacking malignant features: Report of a rare case with review
      of literature.
AB  - We reported a case of meningioma with rhabdoid morphology but lacking
      histological features of malignancy in arising from the spinal cord in a 28-year
      old male. The tumor showed light microscopic, immunohistochemical evidence of
      meningothelial differentiation together with diffuse areas exhibiting rhabdoid
      morphology. The rhabdoid areas were characterized by cells with large cytoplasmic
      eosinophilic inclusions and eccentric nuclei. Unlike most cases reported in the
      literature, this case lacked significant mitotic activity and other atypical
      features. The diagnostic and prognostic significance of this tumor entity is
      discussed along with a review of the literature. 

PMID- 25972961
TI  - Primary hydatid cyst of brain: Two cases report.
AB  - Brain involvement with hydatid disease occurs in 1-2% of all Echinococcus
      granulosus infections. Isolated cerebral hydatid disease is a rare manifestation
      of it. In this report, we analyze two cases of isolated cerebral hydatid cysts
      and discuss their mode of presentation, radiological features, operative
      procedure and outcome. In our two cases, radiological features and surgical
      approaches were different from one another. The literature concerning isolated
      cerebral hydatid disease is reviewed. 

PMID- 25972962
TI  - Occam's razor in the management of ventriculoperitoneal shunt dysfunction:
      Diagnosis and management of an unusual pediatric case.
AB  - Ventriculoperitoneal (VP) shunt surgery is probably the commonest surgical
      procedure in neurosurgery. Belying its technical simplicity is the myriad
      complications associated with it. Shunt malfunction is a common complication
      associated with this surgery, second only to shunt related infections, which may
      be associated with it. Sterile cerebrospinal fluid (CSF) eosinophilia (CE) has
      been reported with VP shunts, which may or may not be related to the dysfunction.
      Eosinophilia in the CSF has also been associated with a number of other
      conditions including parasitic infestations in the brain. This may be unrelated
      to the shunt surgery. We present a case of a child, operated earlier for
      hydrocephalus, who presented with sub-acute loss of vision and bilateral
      oculomotor paresis. CSF from a chamber tap revealed eosinophilia. The commonest
      presenting symptom of shunt malfunction is raised intracranial pressure. There
      are no reports in the literature of VP shunt malfunction presenting with
      bilateral oculomotor paresis and decreased visual acuity. The associated CE
      complicated the clinical picture, especially since the initial brain radiology
      was normal. We discuss the clinical differential diagnosis of this very
      interesting presentation, management dilemmas and outcome in this child. This
      rare clinical presentation was found to be the result of a shunt malfunction and
      not due to any rare parasitic infestation of the brain. Occam's razor dictates
      that the simplest explanation in a given situation is usually the most accurate,
      as is seen in this case. 

PMID- 25972963
TI  - Relevance of anamnesis and of biomarkers in the assessment of smoking among
      patients with airway disease.

PMID- 25972964
TI  - Respiratory muscles: myths and secrets.

PMID- 25972965
TI  - Diagnostic methods to assess inspiratory and expiratory muscle strength.
AB  - Impairment of (inspiratory and expiratory) respiratory muscles is a common
      clinical finding, not only in patients with neuromuscular disease but also in
      patients with primary disease of the lung parenchyma or airways. Although such
      impairment is common, its recognition is usually delayed because its signs and
      symptoms are nonspecific and late. This delayed recognition, or even the lack
      thereof, occurs because the diagnostic tests used in the assessment of
      respiratory muscle strength are not widely known and available. There are various
      methods of assessing respiratory muscle strength during the inspiratory and
      expiratory phases. These methods are divided into two categories: volitional
      tests (which require patient understanding and cooperation); and non-volitional
      tests. Volitional tests, such as those that measure maximal inspiratory and
      expiratory pressures, are the most commonly used because they are readily
      available. Non-volitional tests depend on magnetic stimulation of the phrenic
      nerve accompanied by the measurement of inspiratory mouth pressure, inspiratory
      esophageal pressure, or inspiratory transdiaphragmatic pressure. Another method
      that has come to be widely used is ultrasound imaging of the diaphragm. We
      believe that pulmonologists involved in the care of patients with respiratory
      diseases should be familiar with the tests used in order to assess respiratory
      muscle function.Therefore, the aim of the present article is to describe the
      advantages, disadvantages, procedures, and clinical applicability of the main
      tests used in the assessment of respiratory muscle strength. 

PMID- 25972966
TI  - Comparison between objective measures of smoking and self-reported smoking status
      in patients with asthma or COPD: are our patients telling us the truth?
AB  - OBJECTIVE: Smoking prevalence is frequently estimated on the basis of self
      reported smoking status. That can lead to an underestimation of smoking rates.
      The aim of this study was to evaluate the difference between self-reported
      smoking status and that determined through the use of objective measures of
      smoking at a pulmonary outpatient clinic. METHODS: This was a cross-sectional
      study involving 144 individuals: 51 asthma patients, 53 COPD patients, 20 current
      smokers, and 20 never-smokers. Smoking status was determined on the basis of self
      reports obtained in interviews, as well as through tests of exhaled carbon
      monoxide (eCO) and urinary cotinine. RESULTS: All of the asthma patients and COPD
      patients declared they were not current smokers. In the COPD and asthma patients,
      the median urinary cotinine concentration was 167 ng/mL (range, 2-5,348 ng/mL)
      and 47 ng/mL (range, 5-2,735 ng/mL), respectively (p < 0.0001), whereas the
      median eCO level was 8 ppm (range, 0-31 ppm) and 5 ppm (range, 2-45 ppm),
      respectively (p < 0.05). In 40 (38%) of the patients with asthma or COPD (n =
      104), there was disagreement between the self-reported smoking status and that
      determined on the basis of the urinary cotinine concentration, a concentration >
      200 ng/mL being considered indicative of current smoking. In 48 (46%) of those
      104 patients, the self-reported non-smoking status was refuted by an eCO level >
      6 ppm, which is also considered indicative of current smoking. In 30 (29%) of the
      patients with asthma or COPD, the urinary cotinine concentration and the eCO
      level both belied the patient claims of not being current smokers. CONCLUSIONS:
      Our findings suggest that high proportions of smoking pulmonary patients with
      lung disease falsely declare themselves to be nonsmokers. The accurate
      classification of smoking status is pivotal to the treatment of lung diseases.
      Objective measures of smoking could be helpful in improving clinical management
      and counseling.

PMID- 25972967
TI  - Assessment of quality of life in patients with advanced non-small cell lung
      carcinoma treated with a combination of carboplatin and paclitaxel.
AB  - OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is the most common type of lung
      cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy
      therefore being the only treatment option. This study was aimed at evaluating the
      health-related quality of life (HRQoL) of advanced-stage NSCLC patients receiving
      palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a
      multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at
      a public hospital in Rio de Janeiro, Brazil. The European Organization for
      Research and Treatment of Cancer Core Quality of Life Questionnaire was used in
      conjunction with its supplemental lung cancer-specific module in order to assess
      HRQoL. RESULTS: Physical and cognitive functioning scale scores differed
      significantly among chemotherapy cycles, indicating improved and worsened HRQoL,
      respectively. The differences regarding the scores for pain, loss of appetite,
      chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS:
      Chemotherapy was found to improve certain aspects of HRQoL in patients with
      advanced-stage NSCLC.

PMID- 25972968
TI  - Lung-dominant connective tissue disease among patients with interstitial lung
      disease: prevalence, functional stability, and common extrathoracic features.
AB  - OBJECTIVE: To describe the characteristics of a cohort of patients with lung
      dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective
      study of patients with interstitial lung disease (ILD), positive antinuclear
      antibody (ANA) results (>= 1/320), with or without specific autoantibodies, and
      at least one clinical feature suggestive of connective tissue disease (CTD).
      RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a
      diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and
      the median follow-up period was 48 months. During follow-up, 8 patients met the
      criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised
      the LD-CTD group, in which the most prevalent extrathoracic features were
      arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most
      prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro,
      27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted
      values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual
      interstitial pneumonia patterns were found in 45% and 9% of HRCT scans,
      respectively; 36% of the scans were unclassifiable. A similar prevalence was
      noted in histological samples. Diffuse esophageal dilatation was identified in
      52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17
      showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was
      predominance of females and the patients showed mild spirometric abnormalities at
      diagnosis, with differing underlying ILD patterns that were mostly unclassifiable
      on HRCT and by histology. We found functional stability on follow-up. Esophageal
      dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were
      frequent findings and might come to serve as diagnostic criteria.

PMID- 25972969
TI  - Diffuse aspiration bronchiolitis: analysis of 20 consecutive patients.
AB  - OBJECTIVE: Aspiration can cause a variety of pulmonary syndromes, some of which
      are not well recognized. The objective of this study was to assess the
      demographic, clinical, radiological, and histopathological correlates of diffuse
      aspiration bronchiolitis (DAB), a bronchiolocentric disorder caused by recurrent
      aspiration. METHODS: This was a retrospective study of 20 consecutive patients
      with DAB seen at the Mayo Clinic in Rochester, Minnesota, between January 1, 1998
      and June 30, 2014. RESULTS: The median age of the patients was 56.5 years (range,
      22-76 years), and the male/female ratio was 2.3:1.0. In 18 patients, the
      diagnosis of DAB was based on the results of a lung biopsy; in the 2 remaining
      patients, it was based on clinical and radiological features, together with
      documented aspiration observed in a videofluoroscopic swallow study. In 19
      patients (95%), we identified predisposing factors for aspiration, including
      gastroesophageal reflux disease (GERD), drug abuse, and dysphagia. Common
      presenting features included cough, sputum production, dyspnea, and fever. Twelve
      patients (60%) had a history of recurrent pneumonia. In all of the patients,
      chest CT revealed bilateral pulmonary infiltrates consisting of micronodules and
      tree-in-bud opacities. In the majority of patients, interventions aimed at
      preventing recurrent aspiration (e.g., anti-GERD therapies) led to improvement in
      the symptoms of DAB. CONCLUSIONS: Young to middle-aged subjects with recognizable
      predisposing factors for aspiration and who report a history of recurrent
      pneumonia are at increased risk for DAB. Although DAB is not well recognized,
      certain chest CT features are characteristic of the disorder.

PMID- 25972970
TI  - Preventing smoking during pregnancy: the importance of maternal knowledge of the
      health hazards and of the treatment options available.
AB  - OBJECTIVE: To examine the pattern of tobacco use and knowledge about tobacco
      related diseases, as well as to identify popular types of electronic media, in
      pregnant women, in order to improve strategies for the prevention or cessation of
      smoking among such women. METHODS: A cross-sectional study involving 61 pregnant
      women, seen at primary care clinics and at a university hospital, in the city of
      Botucatu, Brazil. For all subjects, we applied the Hospital Anxiety and
      Depression Scale. For subjects with a history of smoking, we also applied the
      Fagerstrom Test for Nicotine Dependence, and we evaluated the level of motivation
      to quit smoking among the current smokers. RESULTS: Of the 61 pregnant women
      evaluated, 25 (40.9%) were smokers (mean age, 26.4 +/- 7.4 years), 24 (39.3%)
      were former smokers (26.4 +/- 8.3 years), and 12 (19.8%) were never-smokers (25.1
      +/- 7.2 years). Thirty-nine women (63.9%) reported exposure to passive smoking.
      Of the 49 smokers/former smokers, 13 (26.5%) were aware of the pulmonary
      consequences of smoking; only 2 (4.1%) were aware of the cardiovascular risks; 23
      (46.9%) believed that smoking does not harm the fetus or newborn infant; 21
      (42.9%) drank alcohol during pregnancy; 18 (36.7%) reported increased cigarette
      consumption when drinking; 25 (51.0%) had smoked flavored cigarettes; and 12
      (24.5%) had smoked a narghile. Among the 61 pregnant women evaluated, television
      was the most widely available and favorite form of electronic media (in 85.2%),
      as well as being the form most preferred (by 49.2%). CONCLUSIONS: Among pregnant
      women, active smoking, passive smoking, and alternative forms of tobacco
      consumption appear to be highly prevalent, and such women seem to possess little
      knowledge about the consequences of tobacco use. Educational programs that
      include information about the consequences of all forms of tobacco use, employing
      new and effective formats tailored to this particular population, should be
      developed, in order to promote smoking prevention and cessation among pregnant
      women. Further samples to explore regional and cultural adaptations should be
      evaluated.

PMID- 25972971
TI  - Congenital thoracic malformations in pediatric patients: two decades of
      experience.

PMID- 25972972
TI  - Cutaneous tuberculosis as metastatic tuberculous abscess.

PMID- 25972973
TI  - Tracheobronchomalacia in a patient on invasive mechanical ventilation: the role
      of electrical impedance tomography in its detection and positive end-expiratory
      pressure titration.

PMID- 25972974
TI  - Cutaneous focal mucinosis of the scalp and adenocarcinoma of the lung:
      association or coincidence?

PMID- 25972976
TI  - A neural network model of reliably optimized spike transmission.
AB  - We studied the detailed structure of a neuronal network model in which the
      spontaneous spike activity is correctly optimized to match the experimental data
      and discuss the reliability of the optimized spike transmission. Two stochastic
      properties of the spontaneous activity were calculated: the spike-count rate and
      synchrony size. The synchrony size, expected to be an important factor for
      optimization of spike transmission in the network, represents a percentage of
      observed coactive neurons within a time bin, whose probability approximately
      follows a power-law. We systematically investigated how these stochastic
      properties could matched to those calculated from the experimental data in terms
      of the log-normally distributed synaptic weights between excitatory and
      inhibitory neurons and synaptic background activity induced by the input current
      noise in the network model. To ensure reliably optimized spike transmission, the
      synchrony size as well as spike-count rate were simultaneously optimized. This
      required changeably balanced log-normal distributions of synaptic weights between
      excitatory and inhibitory neurons and appropriately amplified synaptic background
      activity. Our results suggested that the inhibitory neurons with a hub-like
      structure driven by intensive feedback from excitatory neurons were a key factor
      in the simultaneous optimization of the spike-count rate and synchrony size,
      regardless of different spiking types between excitatory and inhibitory neurons. 

PMID- 25972977
TI  - Control of absence seizures induced by the pathways connected to SRN in
      corticothalamic system.
AB  - The cerebral cortex, thalamus and basal ganglia together form an important
      network in the brain, which is closely related to several nerve diseases, such as
      parkinson disease, epilepsy seizure and so on. Absence seizure can be
      characterized by 2-4 Hz oscillatory activity, and it can be induced by abnormal
      interactions between the cerebral cortex and thalamus. Many experimental results
      have also shown that basal ganglia are a key neural structure, which closely
      links the corticothalamic system in the brain. Presently, we use a
      corticothalamic-basal ganglia model to study which pathways in corticothalamic
      system can induce absence seizures and how these oscillatory activities can be
      controlled by projections from the substantia nigra pars reticulata (SNr) to the
      thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of the
      thalamus. By tuning the projection strength of the pathway "Excitatory pyramidal
      cortex-SRN", "SRN-Excitatory pyramidal cortex" and "SRN-TRN" respectively,
      different firing states including absence seizures can appear. This indicates
      that absence seizures can be induced by tuning the connection strength of the
      considered pathway. In addition, typical absence epilepsy seizure state "spike
      and-slow wave discharges" can be controlled by adjusting the activation level of
      the SNr as the pathways SNr-SRN and SNr-TRN open independently or together. Our
      results emphasize the importance of basal ganglia in controlling absence seizures
      in the corticothalamic system, and can provide a potential idea for the clinical
      treatment. 

PMID- 25972975
TI  - An fMRI study of facial emotion processing in children and adolescents with
      22q11.2 deletion syndrome.
AB  - BACKGROUND: 22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome
      [VCFS]) is a genetic disorder associated with interstitial deletions of
      chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders,
      children with 22q11DS have impairments of face processing, as well as IQ
      independent deficits in visuoperceptual function and social and abstract
      reasoning. These face-processing deficits may contribute to the social
      impairments of 22q11DS. However, their neurobiological basis is poorly
      understood. METHODS: We used event-related functional magnetic resonance imaging
      (fMRI) to examine neural responses when children with 22q11DS (aged 9-17 years)
      and healthy controls (aged 8-17 years) incidentally processed neutral expressions
      and mild (50%) and intense (100%) expressions of fear and disgust. We included 28
      right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including
      nine siblings) controls. RESULTS: Within groups, contrasts showed that
      individuals significantly activated 'face responsive' areas when viewing neutral
      faces, including fusiform-extrastriate cortices. Further, within both groups,
      there was a significant positive linear trend in activation of fusiform
      extrastriate cortices and cerebellum to increasing intensities of fear. There
      were, however, also between-group differences. Children with 22q11DS generally
      showed reduced activity as compared to controls in brain regions involved in
      social cognition and emotion processing across emotion types and intensities,
      including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann
      area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an
      exploratory correlation analysis showed that within 22q11DS children reduced
      activation was associated with behavioural impairment-social difficulties
      (measured using the Total Difficulties Score from the Strengths and Difficulties
      Questionnaire [SDQ]) were significantly negatively correlated with brain activity
      during fear and disgust processing (respectively) in the left precentral gyrus
      (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18),
      and bilateral cerebellum. CONCLUSIONS: Regions involved in face processing,
      including fusiform-extrastriate cortices, anterior cingulate gyri, and
      superomedial prefrontal cortices (BA 6), are activated by facial expressions of
      fearful, disgusted, and neutral expressions in children with 22q11DS but
      generally to a lesser degree than in controls. Hypoactivation in these regions
      may partly explain the social impairments of children with 22q11DS.

PMID- 25972978
TI  - Power spectral density and coherence analysis of Alzheimer's EEG.
AB  - In this paper, we investigate the abnormalities of electroencephalograph (EEG)
      signals in the Alzheimer's disease (AD) by analyzing 16-scalp electrodes EEG
      signals and make a comparison with the normal controls. The power spectral
      density (PSD) which represents the power distribution of EEG series in the
      frequency domain is used to evaluate the abnormalities of AD brain. Spectrum
      analysis based on autoregressive Burg method shows that the relative PSD of AD
      group is increased in the theta frequency band while significantly reduced in the
      alpha2 frequency bands, particularly in parietal, temporal, and occipital areas.
      Furthermore, the coherence of two EEG series among different electrodes is
      analyzed in the alpha2 frequency band. It is demonstrated that the pair-wise
      coherence between different brain areas in AD group are remarkably decreased.
      Interestingly, this decrease of pair-wise electrodes is much more significant in
      inter-hemispheric areas than that in intra-hemispheric areas. Moreover, the
      linear cortico-cortical functional connectivity can be extracted based on
      coherence matrix, from which it is shown that the functional connections are
      obviously decreased, the same variation trend as relative PSD. In addition, we
      combine both features of the relative PSD and the normalized degree of functional
      network to discriminate AD patients from the normal controls by applying a
      support vector machine model in the alpha2 frequency band. It is indicated that
      the two groups can be clearly classified by the combined feature. Importantly,
      the accuracy of the classification is higher than that of any one feature. The
      obtained results show that analysis of PSD and coherence-based functional network
      can be taken as a potential comprehensive measure to distinguish AD patients from
      the normal, which may benefit our understanding of the disease. 

PMID- 25972980
TI  - Neural bases of syntax-semantics interface processing.
AB  - The binding problem-question of how information between the modules of the
      linguistic system is integrated during language processing-is as yet unresolved.
      The remarkable speed of language processing and comprehension (Pulvermuller et
      al. 2009) suggests that at least coarse semantic information (e.g. noun animacy)
      and syntactically-relevant information (e.g. verbal template) are integrated
      rapidly to allow for coarse comprehension. This EEG study investigated syntax
      semantics interface processing during word-by-word sentence reading. As alpha
      band neural activity serves as an inhibition mechanism for local networks, we
      used topographical distribution of alpha power to help identify the timecourse of
      the binding process. We manipulated the syntactic parameter of verbal event
      structure, and semantic parameter of noun animacy in reduced relative clauses
      (RRCs, e.g. "The witness/mansion seized/protected by the agent was in danger"),
      to investigate the neural bases of interaction between syntactic and semantic
      networks during sentence processing. The word-by-word stimulus presentation
      method in the present experiment required manipulation of both syntactic
      structure and semantic features in the working memory. The results demonstrated a
      gradient distribution of early components (biphasic posterior P1-N2 and anterior
      N1-P2) over function words "by" and "the", and the verb, corresponding to
      facilitation or conflict resulting from the syntactic (telicity) and semantic
      (animacy) cues in the preceding portion of the sentence. This was followed by
      assimilation of power distribution in the alpha band at the second noun. The
      flattened distribution of alpha power during the mental manipulation with high
      demand on working memory-thematic role re-assignment-demonstrates a state of
      alpha equilibrium with strong functional coupling between posterior and anterior
      regions. These results demonstrate that the processing of semantic and syntactic
      features during sentence comprehension proceeds in highly integrated fashion
      using gating of attentional resources to facilitate rapid comprehension, with
      attentional suppression of global alpha power to facilitate interaction of local
      networks. 

PMID- 25972979
TI  - The graph theoretical analysis of the SSVEP harmonic response networks.
AB  - Steady-state visually evoked potentials (SSVEP) have been widely used in the
      neural engineering and cognitive neuroscience researches. Previous studies have
      indicated that the SSVEP fundamental frequency responses are correlated with the
      topological properties of the functional networks entrained by the periodic
      stimuli. Given the different spatial and functional roles of the fundamental
      frequency and harmonic responses, in this study we further investigated the
      relation between the harmonic responses and the corresponding functional
      networks, using the graph theoretical analysis. We found that the second harmonic
      responses were positively correlated to the mean functional connectivity,
      clustering coefficient, and global and local efficiencies, while negatively
      correlated with the characteristic path lengths of the corresponding networks. In
      addition, similar pattern occurred with the lowest stimulus frequency (6.25 Hz)
      at the third harmonic responses. These findings demonstrate that more efficient
      brain networks are related to larger SSVEP responses. Furthermore, we showed that
      the main connection pattern of the SSVEP harmonic response networks originates
      from the interactions between the frontal and parietal-occipital regions.
      Overall, this study may bring new insights into the understanding of the brain
      mechanisms underlying SSVEP. 

PMID- 25972981
TI  - Deterministic convergence of chaos injection-based gradient method for training
      feedforward neural networks.
AB  - It has been shown that, by adding a chaotic sequence to the weight update during
      the training of neural networks, the chaos injection-based gradient method
      (CIBGM) is superior to the standard backpropagation algorithm. This paper
      presents the theoretical convergence analysis of CIBGM for training feedforward
      neural networks. We consider both the case of batch learning as well as the case
      of online learning. Under mild conditions, we prove the weak convergence, i.e.,
      the training error tends to a constant and the gradient of the error function
      tends to zero. Moreover, the strong convergence of CIBGM is also obtained with
      the help of an extra condition. The theoretical results are substantiated by a
      simulation example. 

PMID- 25972982
TI  - Pinning synchronization of coupled inertial delayed neural networks.
AB  - The paper is devoted to the investigation of synchronization for an array of
      linearly and diffusively coupled inertial delayed neural networks (DNNs). By
      placing feedback control on a small fraction of network nodes, the entire coupled
      DNNs can be synchronized to a common objective trajectory asymptotically. Two
      different analysis methods, including matrix measure strategy and Lyapunov
      Krasovskii function approach, are employed to provide sufficient criteria for the
      synchronization control problem. Comparisons of these two techniques are given at
      the end of the paper. Finally, an illustrative example is provided to show the
      effectiveness of the obtained theoretical results. 

PMID- 25972983
TI  - EEG oscillations reflect task effects for the change detection in vocal emotion.
AB  - How task focus affects recognition of change in vocal emotion remains in debate.
      In this study, we investigated the role of task focus for change detection in
      emotional prosody by measuring changes in event-related electroencephalogram
      (EEG) power. EEG was recorded for prosodies with and without emotion change while
      subjects performed emotion change detection task (explicit) and visual probe
      detection task (implicit). We found that vocal emotion change induced theta event
      related synchronization during 100-600 ms regardless of task focus. More
      importantly, vocal emotion change induced significant beta event-related
      desynchronization during 400-750 ms under explicit instead of implicit task
      condition. These findings suggest that the detection of emotional changes is
      independent of task focus, while the task focus effect in neural processing of
      vocal emotion change is specific to the integration of emotional deviations. 

PMID- 25972985
TI  - Computational identification of novel microRNAs and their targets in the malarial
      vector, Anopheles stephensi.
AB  - MicroRNAs are a ~22 nucleotide small non-coding RNAs found in animals, plants and
      viruses. They regulate key cellular processes by enhancing, degrading or
      silencing protein coding targets. Currently most of the data on miRNA is
      available from Drosophila . Given their important post-transcriptional role in
      several organisms, there is a need to understand the miRNA mediated processes in
      normal and abnormal conditions. Here we report four novel microRNAs ast - mir -
      2502, ast - mir - 2559, ast - mir - 3868 and ast - mir - 9891 in Anopheles
      stephensi identified from a set of 3,052 transcriptome sequences, showing average
      minimum free energy of -31.8 kcal/mol of duplex formation with mRNA indicating
      their functional relevance. Phylogenetic study shows conservation of sequence
      signatures within the Class Insecta. Furthermore, 26 potential targets of these
      four miRNAs have been predicted that play an important role in the mosquito life
      cycle. This work leads to novel leads and experimental possibilities for improved
      understanding of gene regulatory processes in mosquito. 

PMID- 25972984
TI  - TGF-beta signaling and its role in the regulation of hematopoietic stem cells.
AB  - Transforming growth factor-betas (TGF-betas) and their family members that
      include bone morphogenic proteins and activins have been implicated in the
      regulation of proliferation, hibernation, quiescence and differentiation of
      hematopoietic stem cells (HSCs). Increasing evidence suggests that the
      superfamily of TGF-betas play an integral role in the intercellular cross-talk
      between the stem cells and their microenvironment as well as within the cells at
      an intracellular level. Active sites of hematopoiesis, such as fetal liver and
      bone marrow are known to have abundant presence of TGF-beta indicating their
      importance in the maintenance and regulation of hematopoiesis. One of the
      striking features of TGF-beta superfamily is the variety of effects they evoke,
      contingent on the developing history of the responding cells. In the present
      review, we discuss the Smad-dependent and Smad-independent TGF-beta signaling
      pathways in order to understand and underscore their role in the regulation of
      HSCs. 

PMID- 25972987
TI  - Cheminformatics models based on machine learning approaches for design of
      USP1/UAF1 abrogators as anticancer agents.
AB  - Cancer cells have upregulated DNA repair mechanisms, enabling them survive DNA
      damage induced during repeated rapid cell divisions and targeted chemotherapeutic
      treatments. Cancer cell proliferation and survival targeting via inhibition of
      DNA repair pathways is currently a very promiscuous anti-tumor approach. The
      deubiquitinating enzyme, USP1 is known to promote DNA repair via complexing with
      UAF1. The USP1/UAF1 complex is responsible for regulating DNA break repair
      pathways such as trans-lesion synthesis pathway, Fanconi anemia pathway and
      homologous recombination. Thus, USP1/UAF1 inhibition poses as an efficient anti
      cancer strategy. The recently made available high throughput screen data for anti
      USP1/UAF1 activity prompted us to compute bioactivity predictive models that
      could help in screening for potential USP1/UAF1 inhibitors having anti-cancer
      properties. The current study utilizes publicly available high throughput screen
      data set of chemical compounds evaluated for their potential USP1/UAF1 inhibitory
      effect. A machine learning approach was devised for generation of computational
      models that could predict for potential anti USP1/UAF1 biological activity of
      novel anticancer compounds. Additional efficacy of active compounds was screened
      by applying SMARTS filter to eliminate molecules with non-drug like features. The
      structural fragment analysis was further performed to explore structural
      properties of the molecules. We demonstrated that modern machine learning
      approaches could be efficiently employed in building predictive computational
      models and their predictive performance is statistically accurate. The structure
      fragment analysis revealed the structures that could play an important role in
      identification of USP1/UAF1 inhibitors. 

PMID- 25972986
TI  - Mathematical model of flagella gene expression dynamics in Salmonella enterica
      serovar typhimurium.
AB  - Flagellar assembly in Salmonella is controlled by an intricate genetic and
      biochemical network. This network comprises of a number of inter-connected
      feedback loops, which control the assembly process dynamically. Critical among
      these are the FliA-FlgM feedback, FliZ-mediated positive feedback, and FliT
      mediated negative feedback. In this work, we develop a mathematical model to
      track the dynamics of flagellar gene expression in Salmonella. Analysis of our
      model demonstrates that the network is wired to not only control the transition
      of the cell from a non-flagellated to a flagellated state, but to also control
      dynamics of gene expression during cell division. Further, we predict that FliZ
      encoded in the flagellar regulon acts as a critical secretion-dependent molecular
      link between flagella and Salmonella Pathogenicity Island 1 gene expression.
      Sensitivity analysis of the model demonstrates that the flagellar regulatory
      network architecture is extremely robust to mutations. 

PMID- 25972989
TI  - CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated
      proteins.
AB  - Interactions between proteins largely govern cellular processes and this has led
      to numerous efforts culminating in enormous information related to the proteins,
      their interactions and the function which is determined by their interactions.
      The main concern of the present study is to present interface analysis of
      cardiovascular-disorder (CVD) related proteins to shed lights on details of
      interactions and to emphasize the importance of using structures in network
      studies. This study combines the network-centred approach with three dimensional
      studies to comprehend the fundamentals of biology. Interface properties were used
      as descriptors to classify the CVD associated proteins and non-CVD associated
      proteins. Machine learning algorithm was used to generate a classifier based on
      the training set which was then used to predict potential CVD related proteins
      from a set of polymorphic proteins which are not known to be involved in any
      disease. Among several classifying algorithms applied to generate models, best
      performance was achieved using Random Forest with an accuracy of 69.5 %. The tool
      named CARDIO-PRED, based on the prediction model is present at
      http://www.genomeinformatics.dce.edu/CARDIO-PRED/. The predicted CVD related
      proteins may not be the causing factor of particular disease but can be involved
      in pathways and reactions yet unknown to us thus permitting a more rational
      analysis of disease mechanism. Study of their interactions with other proteins
      can significantly improve our understanding of the molecular mechanism of
      diseases. 

PMID- 25972988
TI  - Boolean network model for GPR142 against Type 2 diabetes and relative dynamic
      change ratio analysis using systems and biological circuits approach.
AB  - Systems biology addresses challenges in the analysis of genomics data, especially
      for complex genes and protein interactions using Meta data approach on various
      signaling pathways. In this paper, we report systems biology and biological
      circuits approach to construct pathway and identify early gene and protein
      interactions for predicting GPR142 responses in Type 2 diabetes. The information
      regarding genes, proteins and other molecules involved in Type 2 diabetes were
      retrieved from literature and kinetic simulation of GPR142 was carried out in
      order to determine the dynamic interactions. The major objective of this work was
      to design a GPR142 biochemical pathway using both systems biology as well as
      biological circuits synthetically. The term 'synthetically' refers to building
      biological circuits for cell signaling pathway especially for hormonal pathway
      disease. The focus of the paper is on logical components and logical circuits
      whereby using these applications users can create complex virtual circuits. Logic
      gates process represents only true or false and investigates whether biological
      regulatory circuits are active or inactive. The basic gates used are AND, NAND,
      OR, XOR and NOT gates and Integrated circuit composition of many such basic gates
      and some derived gates. Biological circuits may have a futuristic application in
      biomedical sciences which may involve placing a micro chip in human cells to
      modulate the down or up regulation of hormonal disease. 

PMID- 25972991
TI  - On Brucella pathogenesis: looking for the unified challenge in systems and
      synthetic biology.
AB  - Brucellosis is a zoonotic infection transmitted to humans from infected animals
      and is one of the widely spread zoonoses. Recently, six species were recognized
      within the genus Brucella wherein B. melitensis, B. suis and B. abortus are
      considered virulent for humans. While these species differ phenotypically by
      their pattern of metabolic activities, there has been an imperative need to
      understand pathogenesis of Brucella species. It has been foreseen that creating a
      human vaccine for Brucellosis would entail decreased dose of antibiotics. However
      the emerging role of Brucella pathogenesis still centers on isolation of the
      organism and various diagnostic tests thereby leading to varying strategies of
      treatment cycle. In view of disease heterogeneity, we focus systems and synthetic
      biology challenges that might improve our understanding the Brucella
      pathogenesis. 

PMID- 25972990
TI  - In silico study of peptide inhibitors against BACE 1.
AB  - Peptides are increasingly used as inhibitors of various disease specific targets.
      Several naturally occurring and synthetically developed peptides are undergoing
      clinical trials. Our work explores the possibility of reusing the non-expressing
      DNA sequences to predict potential drug-target specific peptides. Recently, we
      experimentally demonstrated the artificial synthesis of novel proteins from non
      coding regions of Escherichia coli genome. In this study, a library of synthetic
      peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and
      screened against Beta-secretase 1 protein, a known drug target for Alzheimer's
      disease (AD). Secondary and tertiary protein structure predictions followed by
      protein-protein docking studies were performed to identify the most promising
      enzyme inhibitors. Interacting residues and favorable binding poses of lead
      peptide inhibitors were studied. Though initial results are encouraging,
      experimental validation is required in future to develop efficient target
      specific inhibitors against AD. 

PMID- 25972992
TI  - Characterizing the burden of disease of particulate matter for life cycle impact
      assessment.
AB  - Fine particulate air pollution (PM2.5) is a major environmental contributor to
      human burden of disease and therefore an important component of life cycle impact
      assessments. An accurate PM2.5 characterization factor, i.e., the impact per kg
      of PM2.5 emitted, is critical to estimating "cradle-to-grave" human health
      impacts of products and processes. We developed and assessed new characterization
      factors (disability-adjusted life years (DALY)/kgPM2.5 emitted), or the products
      of dose-response factors (deaths/kgPM2.5 inhaled), severity factors (DALY/death)
      and intake fractions (kgPM2.5 inhaled/kgPM2.5 emitted). In contrast to previous
      health burden estimates, we calculated age-specific concentration- and dose
      response factors using baseline data, from 63 U.S. metropolitan areas, consistent
      with the U.S. study population used to derive the relative risk. We also
      calculated severity factors using 2010 Global Burden of Disease data. Multiplying
      the revised PM2.5 dose-responses, severity factors and intake fractions yielded
      new PM2.5 characterization factors that are higher than previous factors for
      primary PM2.5 but lower for secondary PM2.5 due to NOx. Multiplying the
      concentration-response and severity factors by 2005 ambient PM2.5 concentrations
      yielded an annual U.S. burden of 2,000,000 DALY, slightly lower than previous
      U.S. estimates. The annual U.S. health burden estimated from PM emissions and
      characterization factors was 2.2 times higher.

PMID- 25972993
TI  - Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1.
AB  - The TRPV4 cation channel, a member of the TRP vanilloid subfamily, is expressed
      in a broad range of tissues where it participates in the generation of a Ca2+
      signal and/or depolarization of membrane potential. Here, we identified stromal
      interaction molecule 1 precursor (STIM1) as an auxiliary protein of this
      epithelial Ca2+channel using confocal microscopy analysis and GST pull-down
      assay. The STIM1 protein associates specifically with the C-terminal tail of
      TRPV4 to form a complex. In previous reports, we demonstrated that the serine824
      residue of TRPV4 is one of the target phosphorylation sites of
      serum/glucocorticoid regulated kinase 1 (SGK1). In this report we further
      identified the role of serine 824 phosphorylation. The TRPV4 mutant S824D (not
      S824A) exhibited a diminished capacity to bind STIM1. Using GST pull-down and co
      immunoprecipitation assays, we demonstrated that STIM1 is part of the TRPV4
      protein complex. Our observations clearly suggest that the formation of a complex
      between TRPV4 and STIM1 and its plasma membrane localization are regulated
      through phosphorylation of serine824 of TRPV4, and that the STIM1-TRPV4 complex
      plays crucial roles in routing TRPV4 to the plasma membrane from the endoplasmic
      reticulum and in maintaining its function. 

PMID- 25972994
TI  - Characterization of chromosomal translocation breakpoint sequences in solid
      tumours: "an in silico analysis".
AB  - Chromosomal translocations that results in formation and activation of fusion
      oncogenes are observed in numerous solid malignancies since years back.
      Expression of fusion kinases in these cancers drives the initiation & progression
      that ultimately leads to tumour development and thus comes out to be clinically
      imperative in terms of diagnosis and treatment of cancer. Nonetheless, molecular
      mechanisms beneath these translocations remained unexplored consequently limiting
      our knowledge of carcinogenesis and hence is the current field where further
      research is required. The issue of prime focus is the precision with which the
      chromosomes breaks and reunites within genome. Characterization of Genomic
      sequences located at Breakpoint region may direct us towards the thorough
      understanding of mechanism leading to chromosomal rearrangement. A unique
      computational multi-parametric analysis was performed for characterization of
      genomic sequence within and around breakpoint region. This study turns out to be
      novel as it reveals the occurrence of Segmental Duplications flanking the
      breakpoints of all translocation. Breakpoint Islands were also investigated for
      the presence of other intricate genomic architecture and various physico-chemical
      parameters. Our study particularly highlights the probable role of SDs and
      specific genomic features in precise chromosomal breakage. Additionally, it
      pinpoints the potential features that may be significant for double-strand breaks
      leading to chromosomal rearrangements. 

PMID- 25972996
TI  - Development of a KLD-12 polypeptide/TGF-beta1-tissue scaffold promoting the
      differentiation of mesenchymal stem cell into nucleus pulposus-like cells for
      treatment of intervertebral disc degeneration.
AB  - OBJECTIVE: To develop tissue engineering scaffolds consisting of self-assembling
      KLD-12 polypeptide/TGF-beta1 nanofiber gel, for the induction of mesenchymal stem
      cell (MSCs) differentiation into nucleus pulposus (NP)-like cells. METHODS: The
      release of TGF-beta1 from KLD-12 polypeptide gels containing varying TGF-beta1
      concentrations was detected by ELISA. MSCs were isolated with a density gradient
      method and their differentiation into NP-like cells was analyzed in KLD-12
      polypeptide/TGF-beta1- or KLD-12 polypeptide control nanofiber-gel 3D-cultures.
      The Alcianblue method, Real-time quantitative PCR (RT-qPCR), and
      immunocytochemistry were used to measure the expression of extracellular matrix
      (ECM) molecules, such as aggrecan, glycosaminoglycans (GAGs), and type II
      collagen. RESULTS: ELISA results documented favorable time-dependent release
      characteristics of TGF-beta1 in the KLD-12 polypeptide/TGF-beta1 gel scaffolds.
      The results of CCK-8 cell proliferation assay showed the TGF-beta1 containing
      scaffolds induced higher growth rate in MSCs compared to the control group.
      Calcein-AM/PI fluorescent staining showed: the cells in the gel grew well,
      maintaining the circular shape of cells, and the spindle and fusiform shape of
      cells on the gel edges. The cell viability displayed a survival rate of 89.14% +/
      2.468 for the TGF-beta1 group with no significant difference between the two
      groups at 14 d of culture. The production of ECM was monitored showing higher
      expression of GAGs in the TGF-beta1 group (P < 0.01) with highest amounts at 10 d
      and 14 d compared to 4 d and 7 d (P < 0.05). Real-time PCR results revealed that
      the expression levels of collagen II and aggrecan mRNA were higher in the TGF
      beta1 group (P < 0.05). Finally, immunocytochemical staining of collagen II
      confirmed the higher expression levels. CONCLUSION: A scaffold containing a KLD
      12 polypeptide/TGF-beta1-nanofiber gel and MSCs differentiated into NP-like cells
      is able to produce ECM and has the potential to serve as a three-dimensional (3
      D) support scaffold for the filling of early postoperative residual cavities and
      the treatment of intervertebral disc degeneration.

PMID- 25972997
TI  - Changed profile of microRNAs in acute lung injury induced by cardio-pulmonary
      bypass and its mechanism involved with SIRT1.
AB  - OBJECTIVE: Acute lung injury (ALI) is a severe complication for patients
      undergoing cardiac surgery necessitating cardio-pulmonary bypass (CPB), however,
      the possible relationship between microRNAs change and ALI induced by CPB is
      still not completely understood. OBJECTIVE: the aim of this study is to determine
      the microRNAs level changes in patients with ALI induced by CPB and its involved
      mechanism. METHODS: We collected blood samples from 45 patients and performed
      microRNA microarray experiments to determine the microRNAs level changes in
      patients with ALI induced by CPB then the result was verified by quantitative
      real-time PCR (qRT-PCR). Plasma TNF-alpha level and respiration parameters
      including respiration index (RI) and oxygenation index (OI) were measured at five
      different time points before or after CPB. Meanwhile the correlationship between
      significantly changed microRNAs and TNF-alpha level and respiration parameters
      was analyzed. Further more, we transfected miR-320 mimic and inhibitor into A549
      cells and observed the proliferation inhibition and apoptosis change caused by
      oxygen-glucose deprivation/reperfusion. Finally we using dual-luciferase reporter
      assay, qRT-PCR and western blot investigated the potential target of miR-320.
      RESULTS: The level of miR-320 was higher in CPB caused ALI with the most
      significance. Correlation analysis found that the level of miR-320 was positively
      associated with TNF-alpha and RI (r = 0.649 and 0.564, P < 0.05), but negative
      correlated with OI (r = -0.638, P < 0.05). In A549 cells, up-regulated miR-320
      induced proliferation inhibition and more apoptosis. SIRT1 may be a target of miR
      320 and higher miR-320 resulted in lower expression of SIRT both in mRNA and
      protein level. CONCLUSION: miR-320 may mediate the ALI after CPB in which
      alveolar epithelial cells are injured via down-regulating SIRT1.

PMID- 25972998
TI  - Myricetin and methyl eugenol combination enhances the anticancer activity, cell
      cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer
      cell lines.
AB  - Drug combination therapies are common practice in the treatment of cancer. In
      this study, we evaluated the anticancer effects of myricetin (MYR), methyl
      eugenol (MEG) and cisplatin (CP) both separately as well as in combination
      against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance
      the anticancer activity of CP against cervical cancer cells, we treated HeLa
      cells with MYR and MEG alone or in combination with cisplatin and evaluated cell
      growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5
      diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and
      fluorescence microscopy. The results revealed that, as compared to single drug
      treatment, the combination of MYR or MEG with CP resulted in greater effect in
      inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction,
      Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss
      were systematically studied to reveal the mechanisms of synergy between MYR, MEG
      and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis
      induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR
      staining. The combination treatment also increased the number of cells in G0/G1
      phase dramatically as compared to single drug treatment. Mitochondrial membrane
      potential loss (LambdaPsim) as well as Caspase-3 activity was much higher in
      combination treatment as compared to single drug treatment. Findings of this
      investigation suggest that MYR and MEG combined with cisplatin is a potential
      clinical chemotherapeutic approach in human cervical cancer. 

PMID- 25972995
TI  - Ca(2+) and ion channels in hypoxia-mediated pulmonary hypertension.
AB  - Alveolar hypoxia, a consequence of many lung diseases, can have adverse effects
      on the pulmonary vasculature. The changes that occur in the pulmonary circulation
      with exposure to chronic hypoxia include reductions in the diameter of the
      pulmonary arteries due to structural remodeling of the vasculature. Although the
      structural and functional changes that occur in the development of pulmonary
      hypertension have been well investigated, less is known about the cellular and
      molecular mechanisms of this process. This review will discuss the role of
      several potassium and calcium channels in hypoxic pulmonary vasoconstriction,
      both in elevating calcium influx into pulmonary artery smooth muscle cells
      (PASMCs). In addition to other signal transduction pathways, Ca(2+) signaling in
      PASMCs plays an important role in the development and progression of pulmonary
      hypertension due to its central roles in vasoconstriction and vascular
      remodeling. This review will focus on the effect of chronic hypoxia on ion
      channels and the potential pathogenic role of Ca(2+) signaling and regulation in
      the progression of pulmonary hypertension. 

PMID- 25972999
TI  - Effects of ischemic preconditioning on the systemic and renal hemodynamic changes
      in renal ischemia reperfusion injury.
AB  - BACKGROUND: Ischemic preconditioning (IPC) could protect against subsequent renal
      ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain
      far from complete. Hence, we explored the effects of IPC on the renal and
      systemic hemodynamic changes, renal function and morphology, as well the
      involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and
      nitric oxide (NO). METHODS: Male Sprague-Dawley rats were randomly divided into
      five groups after right-side nephrectomy: Sham group (surgery without vascular
      clamping); IRI group (the left renal artery was clamped for 45 min); IPC group
      (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle
      group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L
      arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC).
      The renal and systemic hemodynamic parameters, renal function and morphology, as
      well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the
      indicated time points after reperfusion. RESULTS: IPC rats exhibited significant
      improvements in renal function, morphology, and renal artery blood flow (RABF),
      without obvious influence on the systemic hemodynamics and renal vein blood flow.
      Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of
      IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully
      abolished by the administration of L-NAME. CONCLUSIONS: The results suggest that
      IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated
      NO production, thereby alleviating the renal dysfunction and histological damage
      caused by IRI.

PMID- 25973000
TI  - Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via
      regulation of HMGB1/TLR4/NF-kappaB signaling pathway.
AB  - BACKGROUND: To investigate whether hyperbaric oxygen (HBO) intervention affects
      the expressions of inflammatory cytokines, HMGB1/TLR4/NF-kappaB, and arrests
      secondary spinal cord injury (SCI). METHODS: One hundred and twenty healthy adult
      SD rats were randomly divided into four groups: sham, sham + HBO, SCI, and SCI +
      HBO. Each group was then randomly divided into five subgroups of 6 rats each
      according to the following time points: 1, 2, 3, 7, and 14 d post injury.
      Functional recovery of the hindlimb was assessed by Basso, Beattie, and Bresnahan
      (BBB) scores at different time points after SCI. The expression of HMGB1, TLR4,
      and NF-kappaB in the spinal cord tissue was determined by fluorescence
      quantitative PCR, western blot, immunohistochemistry, and ELISA. RESULTS: The
      gene expressions of TLR4, HMGB1, and NF-kappaB (P < 0.01) and the TLR4 protein
      expression were significantly high after SCI. HBO intervention significantly
      decreased all the four parameters at 3, 7, and 14 d post injury (P < 0.05). A
      significant positive correlation (P < 0.01) was observed between the following:
      HMGB1 mRNA, TLR4 mRNA and TLR4 protein; HMGB1 mRNA and NF-kappaB mRNA; and TLR4
      protein and NF-kappaB mRNA. BBB score was negatively correlated with HMGB1, TLR4
      protein and NF-kappaB levels. HBO intervention significantly improved the BBB
      scores at 7 and 14 d post injury (P < 0.05). CONCLUSIONS: Hyperbaric oxygen
      reduced the expressions of HMGB1, TLR4, and NF-kappaB and reduced secondary SCI
      as measured using BBB scores.

PMID- 25973001
TI  - Apoptosis prediction via inhibition of AKT signaling pathway by neogrifolin.
AB  - Neogrifolin, a natural biologically active substance isolated from the edible
      bodies of the mushroom Albatrellus confluens, has been shown to possess several
      pharmacological properties. No studies were investigated against osteosarcoma
      cancer. Hence, in this study, we investigated the apoptosis-inducing effects and
      the mechanisms of neogrifolin on human osteosarcoma cells. Our results
      demonstrated that neogrifolin induced concentration- and time-dependent
      suppression of proliferation. Further, induction of apoptosis in U2OS and MG63
      osteosarcoma cell lines were also observed. Neogrifolin induced the release of
      cytochrome c accompanied by activation of caspase-9, caspase-3 and cleavage of
      poly (ADP-ribose) polymerase (PARP). In addition, z-VAD-fmk, a universal
      inhibitor of caspases, prevented caspase-3 activation and PARP cleavage and
      inhibited neogrifolin-induced cell growth inhibition. Furthermore, neogrifolin
      treatment resulted in a reduction of phosphorylated AKT level, FOXO transcription
      factor, and glycogen synthase kinase 3 (GSK3). Knockdown of GSK3 with siRNA
      inhibited the apoptotic effects of neogrifolin. On the other hand, neogrifolin
      treatment also down-regulated the expression of the inhibitor of apoptosis
      protein (IAP) in both osteosarcoma cells. Collectively, our results suggested
      that neogrifolin is a potential candidate for osteosarcoma. 

PMID- 25973002
TI  - Vascular endothelial growth factor receptor-2 inhibitor cediranib causes
      regression of endometriotic lesions in a rat model.
AB  - Vascular endothelial growth factor (VEGF) receptor-2 plays an essential role in
      angiogenesis, and it also expressed in the glandular epithelium and stromal cells
      of ectopic endometrium. Cediranib is a protein tyrosine kinase inhibitor that
      potently inhibits VEGF receptor-2, but there is no study about its effects on the
      endometriosis. We induced endometriosis on both sides of the abdominal wall in 20
      female Sprague-Dawley rats and randomly divided them into 2 groups. They were
      administered: cediranib 4 mg/kg/day (group 1), equal saline (group 2) for 12
      days. Then, the lesion volumes were calculated, and Masson trichrome was used to
      detect fibrosis. Angiogenesis was evaluated by CD-31 immunohistochemistry and
      serum VEGF levels. Proliferation was indicated by proliferating cell nuclear
      antigen immunohistochemistry. Apoptosis was measured by a TUNEL assay and cleaved
      caspase-3 immunohistochemistry. In the treatment group, the lesion volumes were
      smaller (P < 0.05), and the degree of fibrosis was greater. The microvessel
      density was lower (P < 0.05) than control, however, serum VEGF was up-regulated
      by a negative feedback mechanism (P < 0.01). In addition, proliferation was
      significantly suppressed (P < 0.01), and apoptosis in the lesions was more
      obvious in the treatment group. These data indicated that cediranib can inhibit
      development of endometriotic lesions in rats. 

PMID- 25973003
TI  - miR-205 regulates A549 cells proliferation by targeting PTEN.
AB  - miR-205 is an epithelial-specific miRNA and has been shown to orchestrate some
      cellular processes such as epithelial mesenchymal transition (EMT) and
      differentiation fate of stem cells in mammary gland. miR-205 play a part of a
      tumor suppressor in human cancers. However, the role of miR-205 in lung cancer is
      unclear. In this study, we detected the expression level of miR-205 in 46 cases
      clinical lung cancer specimens and adjacent normal tissues by stem-loop RT-PCR.
      We found that the expression of miR-205 was significantly increased in lung
      cancer specimens compared to adjacent normal tissues (P < 0.01). Furthermore, we
      observed the expressions of PTEN protein and mRNA in lung cancer tissues and
      adjacent normal tissues by methods of western blot and Real time PCR
      respectively. We found that the expressions of PTEN protein and mRNA was
      significantly decreased in lung cancer specimens compared to adjacent normal
      tissues. And then, we found there is a negative relationship between the
      expression of miR-205 and PTEN mRNA in lung cancer by analyzed. To validate
      whether PTEN was direct targets of miR-205, a dual-luciferase reporter assay was
      employed, the result showed that PTEN is a target gene of MiR-205. In subsequent
      experiments, we examined the expressions of PTEN protein and mRNA after
      transfection of miR-205 mimics or inhibitor into A549 cells, and A549 cell
      proliferation was measured by CCK-8 tests. We found that the expression of PTEN
      protein and mRNA in A549 cells were significantly down-regulated or up-regulated
      after miR-205 mimics and miR-205 inhibitors transfected into, and miR-205 could
      inhibits A549 cells proliferation. These results indicate that miR-205 might
      inhibitor the proliferation of A549 cells by regulating the expression of PTEN. 

PMID- 25973004
TI  - Tetraspanin CD63 is a regulator of HIV-1 replication.
AB  - Macrophages and CD4(+) T-cells are the major reservoirs for HIV-1 infection. CD63
      is a tetraspanin transmembrane protein, which has been shown to play an essential
      role during HIV-1 replication in macrophages. In this study, we further confirm
      the requirement of CD63 in HIV-1 replication events in primary human CD4(+) T
      cells, dendritic cells, and a CD4(+) cell line. Most interestingly, we also show
      the evidences for the co-localization and internalization of CD63 and HIV-1 major
      receptor CD4 in primary human macrophages and CD4(+) cell line by confocal
      microscopy and Co-Immunoprecipitation assay. Analysis revealed that CD63-depleted
      CD4(+) T-cells, dendritic cells, and a cell line showed significant decrease in
      HIV-1 production. Further analysis showed that CD63 down regulation reduced
      production of the early HIV protein Tat, and affected HIV protein Gag by CD63-Gag
      interaction. In agreement, CD63 silencing also inhibited production of the late
      protein p24. Furthermore, we revealed that CD63 silencing has no effect on HIV-1
      replication with extensive viral challenge (MOI > 0.2). These findings suggest
      that CD63 plays a dual-role both in early and late HIV-1 life cycle with a range
      of HIV-1 infection (MOI < 0.2). 

PMID- 25973005
TI  - Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis.
AB  - In order to explore the role of innate immunity in the remodeling of CRS (chronic
      rhinosinusitis), we investigated the correlation between TLR2, TLR4 and
      remodeling involved cytokines and histopathological features. Immunohistochemical
      staining was applied to detect the expression of TLR2, TLR4 and TGF-beta1. Masson
      staining was used for observing the collagen deposition. The other
      histopathologic features of remodeling were observed by hemotoxylin and eosin
      (HE) staining. Nasal epithelial cell culture was used to elucidate the effect of
      TLR2, TLR4 agonists and inhibitors on the expression of TGF-beta1 and MMP-9. The
      association study showed that the significantly higher expression of TLR2, TLR4,
      TGF-beta1 and collagen appeared in CRSsNP (chronic rhinosinusitis without nasal
      polyps) patients compared with CRSwNP (chronic rhinosinusitis with nasal polyps)
      patients. In CRSsNP, patients with a severe epithelial damage (score 3) had a
      significantly higher expression of TLR2 than patients with mild epithelial damage
      (score <= 2) (P < 0.05). Moreover the expression of TLR2 correlated negatively
      with squamous hyperplasia in CRSsNP, and positively with gland hyperplasia in
      CRSwNP. The expression of TLR2 and TLR4 was closely related to neutrophil
      infiltration in CRSsNP (P < 0.01). TGF-beta1 was downregulated by TLR2 agonist in
      CRSwNP and upregulated by TLR4 agonist in CRSsNP (P < 0.05). MMP-9 was
      upregulated by TLR4 agonist in CRSwNP (P < 0.05). TLR2 and TLR4 had close
      relationship with TGF-beta1 and the histologic features of remodeling, especially
      collagen deposition and neutrophil infiltration in CRSsNP. The innate immunity
      could influence the histologic characteristics and involved cytokines through
      TLR2 and TLR4 in the remodeling of CRS. 

PMID- 25973006
TI  - BQ-869, a novel NMDA receptor antagonist, protects against excitotoxicity and
      attenuates cerebral ischemic injury in stroke.
AB  - Stroke is one of the three diseases that cause human death in current world, and
      it is the common, frequently occurring disease in the middle-old ages. NMDA
      receptors mediate glutamate-induced cell death when intensely or chronically
      activated, which is an important cause of neuronal cell death after acute
      injuries. Here, we demonstrated that BQ-869, a potent NMDA receptor antagonist,
      blocked NMDA receptor in concentration-dependent and dose-dependent manner,
      attenuated NMDA-induced Ca(2+) influx, inhabited NMDAR-mEPSC in hippocampal
      pyramidal neurons, improved athletic ability of rats with MACO, decreased
      infarction size in focal cerebral ischemia rats and reduced stroke mortality.
      Taken together, our data demonstrate the neuroprotective effect of BQ-869 might
      be through inhibiting NMDA-mediated excitotoxicity. These findings indicate that
      BQ-869 is the most potent antagonist of NMDA receptors, and provide new insights
      with potential therapeutic applications for the treatment of stroke. 

PMID- 25973007
TI  - PI3K-Akt1 expression and its significance in liver tissues with chronic
      fluorosis.
AB  - This study was to explore the effect and significance of PI3K signal pathway on
      mechanism of liver injury in chronic fluorosis. We used 48 Sprague-Dawley rats
      which were randomly divided into 4 groups according to the body weight, 12 in
      each group, half of male and female. The control group was fed with the solid
      feed (the fluorine content was 1.5 mg/kg). The fluorosis animals were fed with
      the corn containing fluorine content of 17 mg/kg from the endemic fluorosis
      areas. Blocking agent LY294002 was injected in the blocking group and phosphate
      buffer solution was injected in the blocking control in the caudal vein with 10
      mg/kg once every other day in the one week before the end of the experiment. The
      animals were drunk by tap water freely. The fluoride contents of urinary and
      skeletal were determined by the F-ion selective electrode method. The mRNA and
      protein expressions of PI3K, Akt1 in the liver tissues were determined by real
      time polymerase chain reaction, and streptavidin-perosidase and Western blot,
      respectively. Results showed that fluoride contents of the urine and bone were
      increased in the fluorosis compared to those in the control. The expression of
      PI3K and Akt1 mRNA and proteins was significantly increased in fluorosis
      hepatocytes, and lower than that of the fluorosis in the blocking. The apoptosis
      and the intracellular calcium concentration were increased. Therefore, we
      conclude that PI3K-Akt signaling pathway may be one of the signaling pathways in
      the pathogenesis of liver injury caused by fluorosis. 

PMID- 25973008
TI  - Resveratrol attenuates spinal cord injury-induced inflammatory damage in rat
      lungs.
AB  - Spinal cord injury (SCI)-induced systemic inflammatory response affects multiple
      organs outside the spinal cord. Treatment options for such complications are
      lacking. We studied the potential protective effects of resveratrol on SCI
      induced inflammatory damage in rat lungs. Sprague-Dawley rats were subjected to
      weight-drop impact at the T10 vertebral level with administration of resveratrol
      (100 mg/kg) or vehicle (via the intraperitoneal route) immediately after trauma.
      Lung injury was studied by measuring: vascular permeability-related pulmonary
      edema; histopathologic scores, neutrophil infiltration and concentrations of
      inflammatory cytokines in bronchoalveolar fluid; expression of inflammatory
      enzymes and sirtuin (SIRT) 1 as well as nuclear factor-kappa B (NF-kappaB)
      activity in pulmonary tissues. Resveratrol treatment significantly alleviated SCI
      induced pulmonary edema as indicated by the ratio of the wet weight to dry weight
      of lung tissue and pulmonary permeability index. Resveratrol significantly
      reduced neutrophil infiltration and production of inflammatory mediators.
      Resveratrol treatment was accompanied by up-regulation of expression of SIRT1 and
      suppression of NF-kappaB activity in pulmonary tissues. These data suggest that
      resveratrol may protect the lungs from SCI-induced inflammatory damage, and could
      be used as a therapeutic option against pulmonary problems after SCI. 

PMID- 25973009
TI  - M13 phage peptide ZL4 exerts its targeted binding effect on schistosoma japonicum
      via alkaline phosphatase.
AB  - The present study was to determine the targeting effect of M13 phage peptide ZL4
      (MppZL4) on Schistosoma japonicum (S.j). Mice infected with S.j were injected
      with MppZL4. Real-time PCR was used to detect the distribution and metabolism of
      MppZL4 in the livers and lungs of mice. In vivo refusion test was performed to
      detect the targeting of MppZL4. Western blotting was employed to determine the
      expression of MppZL4. Live imaging was used to detect the distribution of
      oligopeptide MppZL4. Immunohistochemistry was employed to determine MppZL4
      location on adult S.j body surface. Gomori method was employed to detect the
      influence of oligopeptide MppZL4 on alkaline phosphatase activity. The
      distribution and metabolism of MppZL4 and M13KE are not significantly different
      from each other at each time point. The abundance of MppZL4 is changed as S.j
      migrates in mice. The targeted binding effect of MppZL4 varies at different
      stages. ZL4 oligopeptide targets S.j in mice. The specific binding sites of
      MppZL4 on S.j body are mainly located in syncytial cells. The binding sites of
      MppZL4 on S.j body surface might be ALP or ALP-related proteins. MppZL4 had
      targeted binding effect on S.j with its binding site being associated with
      proteins related to S.j alkaline phosphatase. S.j tegument had a specifically
      binding site with exogenous peptides, offering new means to explore the
      interactions between hosts and parasites. Additionally, MppZL4 can possibly be
      used as targeting molecules in worm-resistant drugs or as tracing molecules in
      imaging diagnosis technologies. 

PMID- 25973010
TI  - BTLA associates with increased Foxp3 expression in CD4(+) T cells in dextran
      sulfate sodium-induced colitis.
AB  - Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis
      involves a variety of genetic, environmental, and immunological factors such as T
      helper cells and their secreted cytokines. B and T lymphocyte attenuator (BTLA)
      is an immunoregulatory receptor that has a strong suppressive effect on T-cell
      function. However the role of BTLA in UC remains poorly understood. Here we
      demonstrated that the frequency of BTLA-expressing CD3(+) T cells, especially
      CD4(+) T cells, increased in blood and mucosa in mice with DSS-induced colitis.
      The frequency of Foxp3-expressing cells in BTLA+ CD4(+) T cell from lamina
      propria mononuclear cells (LPMCs) was much higher in DSS-treated mice than that
      in controls. Similarly, the proportion of IL-17+ cells in BTLA+ CD4(+) T cells
      from LPMCs in DSS-treated mice is much higher than that in controls, while no
      perceptible difference for the proportion of IFN-gamma+ cells in BTLA+ CD4(+) T
      cells was noted between DSS-treated mice and controls. Treatment of mesalazine,
      an anti-ulcerative colitis drug, down-regulated Foxp3 and IL-17 expression in
      BTLA positive T cells along with attenuated severity for colitis. Our findings
      indicate that BTLA may be involved in the control of inflammatory responses
      through increasing Foxp3 expression, rather than attenuating IL-17 production, in
      DSS-induced colitis. 

PMID- 25973011
TI  - Dihydroartemisinin supresses inflammation and fibrosis in bleomycine-induced
      pulmonary fibrosis in rats.
AB  - Pulmonary fibrosis is a respiratory disease with a high mortality rate and its
      pathogenesis involves multiple mechanisms including epithelial cell injury,
      fibroblast proliferation, inflammation, and collagen coagulation. The treatment
      regimens still fail to recover this disease. We have previously found that
      dihydroartemisinin inhibits the development of pulmonary fibrosis in rats. This
      study aimed to determine the mechanisms of dihydroartemisinin in bleomycin
      induced pulmonary fibrosis. The experimental rats were divided into six groups as
      normal saline control group (NS group), bleomycin group (BLM group),
      dihydroartemisinin-1, -2, or -3 group (DHA-1, DHA-2 and DHA-3 group) and
      dexamethasone group (DXM group). In BLM group, rats were treated with
      intratracheal instillation of bleomycin. NS group received the same volume of
      saline instead of bleomycin. In DHA-1, DHA-2 and DHA-3 group, in addition to
      intratracheal instillation of bleomycin, respectively, dihydroartemisinin (25
      mg/kg, 50 mg/kg, 100 mg/kg daily) was administrated by intraperitoneal
      instillation. In DXM group, rats were treated with intraperitoneal instillation
      of dexamethasone as control. Immunocytochemical assay, reverse transcription PCR
      and western blot were used for detecting the expression of TGF-beta1, TNF-alpha,
      alpha-SMA and NF-kappaB in lung tissues. What's more, morphological change and
      collagen deposition were analyzed by hematoxylin-eosin staining and Masson
      staining. Collagen synthesis was detected by hydroxyproline chromatometry.
      Results showed that dihydroartemisinin significantly decreased the amount of
      inflammatory cytokines and collagen synthesis, and inhibited fibroblast
      proliferation in bleomycin-induced pulmonary fibrosis (P < 0.001). This study
      provides experimental evidence that dihydroartemisinin could decrease cytokines,
      alveolar inflammation and attenuates lung injury and fibrosis. 

PMID- 25973012
TI  - Biocompatibility of porcine small intestinal submucosa and rat endothelial
      progenitor cells in vitro.
AB  - OBJECTIVE: This study investigated the biocompatibility of the small intestinal
      submucosa (SIS) and endothelial progenitor cells (EPCs) by co-cultivating EPCs
      and SIS in vitro and observing EPC growth on the SIS. METHODS: The porcine SIS
      was prepared and bone marrow mononuclear cells (BMMNCs) were isolated from 3 or 4
      week old male SD rats. Cellular morphology was observed by light microscopy and
      scanning electron microscopy (SEM) and viabilities by the MTT assays. Endothelial
      progenitor cells (EPCs) were phenotyped by immunocytochemistry,
      immunofluorescence microscopy and flow cytometry. Vascular lumen formation was
      evaluated by the Matrigel tube formation assays. EPCs were seeded onto the SIS
      and production of angiogenin-1 and endothelial cell growth factor (VEGF) by EPCs
      was examined by ELISA and immunoblotting assays. RESULTS: Light microscopy and
      SEM showed that the mechanically and chemically treated small intestinal
      submucosa was composed of cell-free extracellular matrix. Immunohistochemistry,
      and flow cytometry revealed that the EPCs expressed appropriate surface markers
      including CD34, CD133, and VEGFR-2. Furthermore, the EPCs formed lumen-like
      structures and the SIS significantly enhanced the growth of EPCs in vitro.
      CONCLUSION: SIS has good biocompatibility with EPCs. SIS pre-seeded with EPCs can
      be potentially applied as an alternative scaffold material in artificial blood
      vessel prosthesis.

PMID- 25973013
TI  - Effects of 18alpha-glycyrrhizin on TGF-beta1/Smad signaling pathway in rats with
      carbon tetrachloride-induced liver fibrosis.
AB  - BACKGROUND: Glycyrrhizin has various pharmacological effects including hepato
      protection. This study aimed to investigate the potential mechanism underlying
      the protective effects of 18alpha-glycyrrhizin (18alpha-GL) in rats with carbon
      tetrachloride (CCl4) induced liver fibrosis. METHODS: Male Sprague-Dawley (SD)
      rats were randomly divided into control group, fibrosis group, 25 mg/kg 18alpha
      GL group and 12.5 mg/kg 18alpha-GL group. Rats in experimental groups were
      subcutaneously injected with 40% CCl4 twice weekly for 8 weeks.
      Immunohistochemical examination was carried out to detect the protein expressions
      of collagen I, collagen III, TGF-beta1, p-Smad2, p-Smad3, Smad 7 and SP-1, in the
      liver, and the mRNA and protein expressions of these genes were determined in the
      liver by real time PCR and Western blot assay, respectively. RESULTS: 18alpha-GL
      ameliorated histological changes and significantly suppressed collagen
      deposition. 18alpha-GL significantly decreased the mRNA expressions of TGF-beta1,
      Smad2, Smad3 and SP-1 in the liver. Immunohistochemical staining revealed that
      TGF-beta1, p-Smad2, p-Smad3 and SP-1 expressions reduced following 18alpha-GL
      therapy. Western blot assay showed p-Smad2, p-Smad3, smad2 and smad3 expressions
      decreased after 18alpha-GL treatment. The mRNA and protein expression of Smad7
      remained unchanged. CONCLUSION: 18alpha-GL is able to attenuate CCl4 induced
      liver fibrosis in rat.

PMID- 25973014
TI  - Nephroblastoma overexpressed gene (NOV) enhances RCC cell motility through
      upregulation of ICAM-1 and COX-2 expression via Akt pathway.
AB  - Renal cell carcinoma (RCC) carries a high risk of malignancy and metastasis. The
      inducible isoform of prostaglandin synthase, cyclooxygenase (COX)-2, and ICAM-1
      may be involved in tumor metastasis. CCN3, also called nephroblastoma
      overexpressed gene (NOV), has been found to regulate the proliferation and
      differentiation of cancer cells. The effects of NOV on RCC cell migration and
      expression of COX-2 and ICAM-1 have not described yet in detail. But here, NOV
      was found to promote the migration and expression of COX-2 and ICAM-1 in human
      RCC cells. Akt inhibitor was found to interfere with this NOV-induced migration
      and up-regulation of COX-2 and ICAM-1 in RCC cells. NOV stimulation was here
      found to promote the phosphorylation of Akt. RCC tissue chips were subjected to
      IHC staining, which showed COX-2 expression in RCC tissues to be a significantly
      closely correlated with NOV expression, with significance determined using
      Pearson correlation testing (P < 0.05). The results of the current work indicate
      that NOV activates COX-2 and ICAM-1 through Akt, promoting the migration of RCC
      cells. 

PMID- 25973015
TI  - Silencing of TMSG1 enhances metastasis capacity by targeting V-ATPase in breast
      cancer.
AB  - TMSG1, as a novel tumor metastasis suppressor gene, has been demonstrated to
      closely relate to the metastasis and drug-resistant of breast cancer. However,
      its molecular mechanism is still unclear. In this study, we explored the effect
      of small interference RNA (siRNA) targeting TMSG1 on the invasion of human breast
      carcinoma cell line MCF-7 and its molecular mechanisms associated with the
      extracellular pH. qRT-PCR and Western blot analysis revealed dramatic reduction
      of the levels of TMSG1 mRNA and protein after transfection of siRNA in MCF-7
      cells. Cell migration and invasion were obviously increased by TMSG1 siRNA
      treatment. The activity of vacuolar ATPase (V-ATPase) and MMP-2 was significantly
      increased in MCF-7 cells transfected with the TMSG1 siRNA compared with the
      controls. Furthermore, acidic intracellular environment significantly increased
      the MMP-2 activity and the capacity of cell migration and invasion. In
      conclusion, silencing of TMSG1 increased V-ATPase activity, decreased
      extracellular pH and in turn the activation of secreted MMP-2, which ultimately
      promoted metastasis capacity of breast cancer cell. 

PMID- 25973016
TI  - Two novel mutations in NOTCH3 gene causes cerebral autosomal dominant
      arteriopathy with subcritical infarct and leucoencephalopathy in two Chinese
      families.
AB  - OBJECTIVE: To investigate the genetic pathogenic causes of cerebral autosomal
      dominant arteriopathy with subcritical infarct and leucoencephalopathy (CADASIL)
      in two Chinese families, to provide the molecular basis for genetic counseling
      and antenatal diagnosis. METHODS: The genetic mutation of gene NOTCH3 of
      propositus and family members was analyzed in these two CADASIL families by
      polymerase chain reaction and DNA sequencing technology directly. At the same
      time, the NOTCH3 gene mutation point of 100 healthy collators was detected, to
      explicit the pathogenic mutation by function prediction with Polyphen-2 and SIFT.
      RESULTS: Both propositus of the two families and patients with symptom were all
      accorded with the clinical features of CADASIL. It was shown by DNA sequencing
      that the 19(th) exon [c. 3043 T > A (p.Cys1015Ser)] in gene NOTCH3 of propositus,
      2 patients (II3, III7), and a presymptomatic patient (IV1) in Family I all had
      heterozygosity missense mutation; and the 3(rd) exon [c.316T > G, p. (Cys106Gly)]
      in gene NOTCH3 of the propositus, a patient (IV3) and two presymptomatic patients
      (IV5, 6) in Family II all had heterozygosity missense mutation; and no mutations
      were detected in the 100 healthy collators. It was indicated by analyzing the
      function prediction that the mutation of [c. 3043 T > A (p.Cys1015Ser)] and
      [c.316T > G, p. (Cys106Gly)] may both influence encoding protein in NOTCH3. By
      analysis of the conservatism of mutation point in each species, these two basic
      groups were highly conserved. CONCLUSION: The heterozygosity missense mutation of
      19(th) exon [c. 3043 T > A (p.Cys1015Ser)] and the 3(rd) exon [c.316T > G, p.
      (Cys106Gly)] in NOTCH3 gene are the new pathogenic mutations of CADASIL, and
      enriches the mutation spectrum of NOTCH3 gene.

PMID- 25973017
TI  - MicroRNA-145 suppresses cell migration and invasion by targeting paxillin in
      human colorectal cancer cells.
AB  - A number of cancers show increased expression of paxillin which plays a central
      role in tumor progression, including colorectal cancer. However, the mechanisms
      causing paxillin upregulation remains unclear. In our study, bioinformatics
      analyses suggested that paxillin is predicted to be a direct target of miR-145.
      We firstly identified paxillin as a new target of miR-145 and demonstrated that
      miR-145 inhibits paxillin expression by binding to the paxillin mRNA 3'UTR.
      Therefore, we assume overexpression of paxillin induced by suppression of miR-145
      may promote cell migration and invasion. We detected the expression of paxillin
      and miR-145 in human colorectal cancer tissues by real-time quantitative PCR.
      Higher expression of paxillin and lower expression of miR-145 was observed in
      colorectal cancer tissues than corresponding paracancerous tissue. Moreover, the
      expression of paxillin was negatively correlated with miR-145 expression. A dual
      luciferase reporter assay was used to confirm that paxillin was a direct target
      of miR-145. In CRC cell lines, overexpression of miR-145 could downregulate
      paxillin protein expression levels, and ectopic overexpression of miR-145 mimics
      or inhibitor could inhibit or promote cell migration, invasion, proliferation and
      clone formation in vitro. Taken together, these data suggested that miR-145 plays
      a pivotal role in colon cancer through inhibiting cell proliferation migration
      and invasion, and miR-145 may serve as a tumor suppressor by targeting paxillin
      gene. 

PMID- 25973019
TI  - beta-arrestin 2 is associated with multidrug resistance in breast cancer cells
      through regulating MDR1 gene expression.
AB  - Mutidrug resistance (MDR) severely blocks the successful management of breast
      cancer. Overexpression of MDR1/p-gp accounts for the major factor in the
      development of MDR. beta-arrestin 2 has been reported to widely involve in
      multiple aspects of tumor development. In order to verify whether beta-arrestin 2
      regulates mutidrug resistance in breast cancer, we analyzed the protein
      expression levels of beta-arrestin 2 and MDR1/p-gp by immunohistochemistry in 106
      paraffin-embedded human breast tissue samples. There was a positive correlation
      between beta-arrestin 2 and MDR1/p-gp protein expression (P = 0.016). Changes in
      MDR1/p-gp mRNA and protein levels were examined by quantitative real-time reverse
      polymerase chain reaction (qRT-PCR) and western blotting. Silencing of beta
      arrestin 2 evidently down-regulated the expression of MDR1/p-gp in transfected
      ADM cells. In contrast, overexpression of beta-arrestin 2 had the opposite
      changes in MDA-MB-231 and MCF-7 cells. MTS assay revealed that silencing of beta
      arrestin 2 increased the sensitivity to anti-cancer drugs to some extent. On the
      other hand, overexpression of beta-arrestin 2 had the opposite effects. Our above
      data demonstrate that beta-arrestin 2 plays a vital role in the regulation of
      MDR1/p-gp expression in Breast cancer.

PMID- 25973018
TI  - Elevated HMGB1-related interleukin-6 is associated with dynamic responses of
      monocytes in patients with active pulmonary tuberculosis.
AB  - There were limited studies assessing the role of HMGB1 in TB infection. In this
      prospective study, we aimed to assess the levels of HMGB1 in plasma or sputum
      from active pulmonary tuberculosis (APTB) patients positive for Mtb culture test,
      and to evaluate its relationship with inflammatory cytokines and innate immune
      cells. A total of 36 sputum Mtb culture positive APTB patients and 32 healthy
      volunteers (HV) were included. Differentiated THP-1 cells were treated for 6, 12
      and 24 hrs with BCG at a multiplicity of infection of 10. The absolute values and
      percentages of white blood cells (WBC), neutrophils, lymphocytes, and monocytes
      were detected by an automatic blood analyzer. Levels of HMGB1, IL-6, IL-10 and
      TNF-alpha in plasma, sputum, or cell culture supernatant were measured by ELISA.
      The blood levels of HMGB1, IL-6, IL-10 and TNF-alpha, the absolute values of WBC,
      monocytes and neutrophils, and the percentage of monocytes were significant
      higher in APTB patients than those in HV groups (P < 0.05). The sputum levels of
      HMGB1, IL-10, and TNF-alpha were also significantly higher in APTB patients than
      those in HV groups (P < 0.05). Meanwhile, plasma level of HMGB1, IL-6, and IL-10
      in APTB patients were positively correlated with those in sputum (P < 0.05),
      respectively. IL-6 was positively correlated with HMGB1 both in plasma and sputum
      of APTB patients (P < 0.05). HMGB1 and IL-6 is positively correlated with the
      absolute number of monocytes in APTB patients (P < 0.05). BCG induced HMGB1, IL
      6, IL-10 and TNF-alpha production effectively in PMA-treated THP-1 cells. HMGB1
      may be used as an attractive biomarker for APTB diagnosis and prognosis and may
      reflect the inflammatory status of monocytes in patients with APTB.

PMID- 25973020
TI  - MiR-34a inhibits oral cancer progression partially by repression of interleukin-6
      receptor.
AB  - Previous reports revealed that a significant decrease of miR-34a in oral cancer.
      But the role of miR-34a in oral cancer needs further research. In the present
      study, we will investigate the effect of miR-34a on oral cancer cell phenotypes.
      First, it was verified that miR-34a expression was lower in oral cancer tissues
      compared with their normal controls, so did the oral cancer cells. Next, it was
      showed that miR-34a overexpression in oral cancer cells could inhibit cell
      proliferation, G1 phase arrest, metastasis and epithelial mesenchymal transition.
      It was predicted that interleukin-6-receptor (IL6R) was a potential target gene
      of miR-34a by bioinformatics analysis and identified by luciferase assay. It was
      further showed that miR-34a inhibited oral cancer progression via IL6R.
      Collectively, our findings suggested that miR-34a may function as a tumor
      suppressor in oral cancer by targeting IL6R. 

PMID- 25973021
TI  - PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells
      in zymosan-induced multiple organs dysfunction syndromes.
AB  - This research is to investigate the role of tolerant spleen dendritic cells (DC)
      in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and
      MODS were induced by intraperotineal injection of zymosan. The immunity of DC was
      determined by examining interleukin (IL)-10, IL-12, IL-2, major
      histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death
      ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell
      proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture.
      The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum,
      spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after
      zymosan injection while the IL-12p40 and IL-10 were increased. The expression of
      MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were
      increased at early stage after zymosan injection. At 5 d and 12 d, the expression
      of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was
      increased, accompanied with decreased proliferation of T-cell and decrease of IL
      2 in spleen and serum. Application of PD-L1 antibody improved the above changes.
      At late stage of MODS mice induced by zymosan, the expression of co-stimulators
      and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced
      the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs
      through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell
      activities by tolerant DCs and the immune inhibition. 

PMID- 25973022
TI  - Bile acids but not acidic acids induce Barrett's esophagus.
AB  - Barrett's esophagus (BE) is associated with the development of esophageal
      adenocarcinoma (EAC). Bile acids (BAs) refluxing into the esophagus contribute to
      esophageal injury, which results in BE and subsequent EAC. We developed two
      animal models to test the role of BAs in the pathogenesis of BE. We surgically
      generated BA reflux, with or without gastric acid, in rats. In a second
      experiment, we fed animals separately with BAs and gastric acid. Pathologic
      changes were examined and the expression of Muc2 and Cdx2 in BE tissue was tested
      by immunostaining. Inflammatory factors in the plasma, as well as differentiation
      genes in BE were examined through highly sensitive ELISA and semi-quantitative RT
      PCR techniques. We found that BAs are sufficient for the induction of esophagitis
      and Barrett's-like metaplasia in the esophagus. Overexpression of inflammatory
      cells, IL-6, and TNF-alpha was observed both in animals fed with BAs and
      surgically generated BA reflux. Furthermore, elevated levels of Cdx2, Muc2, Bmp4,
      Kit19, and Tff2 (differentiation genes in BE) were found in BA-treated rats. In
      conclusion, BAs, but not gastric acid, are a major causative factor for BE. We
      confirmed that BAs contribute to the development of BE by inducing the
      inflammatory response in the esophagus. Inhibiting BAs may be a promising therapy
      for BE. 

PMID- 25973023
TI  - High expression of cytoplasmic phosphorylated CSE1L in malignant melanoma but not
      in benign nevi: phosphorylated CSE1L for the discrimination between melanoma and
      benign nevi.
AB  - Melanoma is difficult to treat when it has metastasized. Discrimination between
      melanoma and benign nevi in melanocytic lesions is crucial for identifying
      melanomas and consequently improving melanoma treatment and prognosis. The
      chromosome segregation 1-like (CSE1L) protein has been implicated in cancer
      progression and is regulated by phosphorylation by extracellular signal-regulated
      kinase 1/2 (ERK1/2) signaling, a critical pathway in melanoma progression. We
      studied phosphorylated CSE1L expression in human melanoma and benign nevi
      specimens. Immunohistochemistry with tissue microarray using antibody against
      phosphorylated CSE1L showed that melanomas exhibited considerable staining for
      phosphorylated CSE1L (100%, 34/34), whereas the benign nevi showed only faint
      staining (0%, 0/34). Melanomas mainly exhibited cytoplasmic phospho-CSE1L
      distribution, whereas the benign nevi mainly exhibited nuclear phospho-CSE1L
      distribution. Moreover, immunohistochemistry with anti-CSE1L antibody revealed
      that CSE1L mainly exhibited cytoplasmic/nuclear distribution and nuclear
      distribution was the dominant. Immunofluorescence with B16F10 melanoma cells
      showed cytoplasmic distribution of phospho-CSE1L and nuclear distribution of
      CSE1L. Our results indicated that nuclear CSE1L is mainly non-phosphorylated
      CSE1L and is involved in gene regulation and cytoplasmic CSE1L is mainly
      phosphorylated CSE1L and is involved in cytoplasmic signaling regulation in
      melanocytic tumorigenesis. Furthermore, immunohistochemical analysis of
      cytoplasmic phospho-CSE1L may aid in the diagnosis of melanoma. 

PMID- 25973024
TI  - Inositol hexaphosphate suppresses growth and induces apoptosis in HT-29
      colorectal cancer cells in culture: PI3K/Akt pathway as a potential target.
AB  - BACKGROUND: Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate
      that is present in high amounts in almost all plants and mammalian cells. IP6
      induces apoptosis in multiple types of cancer cells, including prostate cancer,
      breast cancer, skin tumor, liver cancer and colorectal cancer. However, little is
      known regarding the molecular mechanisms of its anticancer effects. Therefore,
      this study was conducted to investigate the activity of IP6 against human
      colorectal cancer cells (HT-29) and to determine whether the IP6 regulates
      apoptosis in HT-29 cells by inhibiting the PI3K/Akt signaling pathway. METHOD: A
      human colorectal cancer cell line (HT-29) was used for the study. HT-29 cells
      were treated with 0, 50, 100, 200, and 400 MUg/mL of IP6. The MTT colorimetric
      assay was used to observe the proliferation of HT-29 in vitro, and flow cytometry
      (FCM) was used to analyze the apoptosis of the HT-29 cells. The relative mRNA
      expression was determined by real-time PCR, and relative protein levels were
      analyzed by Western blot analysis. RESULT: The results of MTT showed that HT-29
      cells underwent inhibition of proliferation after exposure to IP6 (100-400
      MUg/mL) for 12 and 48 h, and this inhibition clearly relied on time and dosage.
      IP6 induced apoptosis in HT-29 cells in a dose-dependent manner. The mRNA and
      protein expression of PI3K and Akt decreased in the groups treated with IP6, and
      IP6 inhibited the phosphorylation of Akt (pAkt), whereas increased the expression
      of its downstream effector, caspase-9. CONCLUSION: Our results suggested that by
      targeting PI3K/Akt pathway, IP6 suppresses cell survival and proliferation, but
      induces death in HT-29 cells.

PMID- 25973025
TI  - Bax inhibitor-1 is overexpressed in non-small cell lung cancer and promotes its
      progression and metastasis.
AB  - Bax inhibitor-1 (BI-1) is a novel anti-apoptotic protein. While the effect of BI
      1 on apoptosis has been extensively studied, less is known about how BI-1 is
      related to oncogenesis and the progression, particularly, the invasion and
      metastasis of cancer. In this study, we investigated the expression and function
      of BI-1 in human non-small cell lung cancer (NSCLC). RT-PCR and
      immunohistochemistry were performed on clinical NSCLC samples to detect BI-1
      expression. Northern blot and Western blot analysis were performed to detect BI-1
      expression of in NSCLC cell lines. Cell proliferation and apoptosis were analyzed
      by flow cytometry. Our results showed that the overexpression of BI-1 was
      significantly related to oncogenesis of NSCLC (P < 0.05). Meanwhile, we
      identified a novel 5'end from normal lung-derived BI-1 transcript, different from
      any transcript deposit in the Genbank, but we detected no mutations in the coding
      sequence and the promoter region of BI-1 and no abnormal splicing of the
      alternative first exon. Ectopic expression of BI-1 changed the proliferation and
      apoptosis of AGZY83-a and Anip973 cells. In conclusion, BI-1 is overexpressed in
      NSCLC and promotes the progression and metastasis of NSCLC. 

PMID- 25973026
TI  - TRAF4 promotes the growth and invasion of colon cancer through the Wnt/beta
      catenin pathway.
AB  - The tumor necrosis factor receptor-associated factor 4 (TRAF4) has been linked to
      carcinogenesis. However, the role of TRAF4 in colon cancer is still unclear.
      Therefore, we investigated the role of TRAF4 in colon cancer and the underlying
      mechanism. In the present study, we found that TRAF4 was overexpressed in colon
      cancer tissues and cells, and small interfering RNA (siRNA)-mediated gene
      knockdown of TRAF4 significantly inhibited cell proliferation, invasion and
      tumorigenesis, both in vitro and in vivo, but induced apoptosis in colon cancer
      cells. Furthermore, siRNA-TRAF4 significantly inhibited the expression levels of
      beta-catenin, cyclinD1, and c-myc proteins in colon cancer cells. Taken together,
      these results suggest that TRAF4 promoted colon cancer cell growth and invasion
      by potentiating the Wnt/beta-catenin pathway, suggesting that TRAF4 may be a
      potential molecular target for colon cancer prevention and therapy. 

PMID- 25973027
TI  - Role of ursolic acid chalcone, a synthetic analogue of ursolic acid, in
      inhibiting the properties of CD133(+) sphere-forming cells in liver stem cells.
AB  - The expression of CD133 decreases with differentiation of tumor cell, indicating
      that CD133 is a specific marker for isolation and identification of CSCs. In the
      present study the effect of Ursolic acid chalcone (UAC) on CD133(+)
      hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal,
      tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The
      results demonstrated that UAC inhibits the expression of CD133(+) in a dose and
      time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was
      significant at 50 MUM and on day 8. The percentage of CD133(+) cells decreased
      from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on
      treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, beta-catenin,
      ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number
      of CK19-positive cells and increased number of CK8/18-positive cells. UAC
      treatment caused a decrease in self-renewal capability and increase in
      sensitivity to doxorubicin and vincristine drugs in CD133(+) HCC CSCs. Therefore,
      UAC can be a potent therapeutic agent to target differentiation of CSC in HCC. 

PMID- 25973028
TI  - Myrtol ameliorates cartilage lesions in an osteoarthritis rat model.
AB  - PURPOSE: The aim of this study is to evaluate the effects of myrtol standardized
      on cartilage lesions in osteoarthritis (OA) rats. METHODS: Fifty-six healthy
      Sprague-Dawley rats were randomly divided into sham group (13 rats) and OA model
      group (43 rats) with interior meniscus excision. Then serum estradiol (E2) and
      glycosaminoglycan (GAG) content in cartilage tissue were measured by
      radioimmunoassay and toluidine blue staining, respectively. After that, the model
      rats were randomly divided into low dose myrtol (LDM) group, middle dose myrtol
      (MDM) group and high dose myrtol (HDM) group (10 rats in each group) with
      treatment of 450 mg/kg, 300 mg/kg and 150 mg/kg myrtol, respectively. Then,
      Mankin scores were used to evaluate lesion extent of knee joint cartilage.
      Expression of tumor necrosis factor alpha (TNF-alpha), transforming growth factor
      beta1 (TGF-beta1), interleukin (IL)-6, Bax and Bcl-2 were investigated using PCR
      gel electrophoresis method. RESULTS: Mankin cores were lower in sham group and
      myrtol group than in model group. There were statistically significant
      differences (P < 0.01) between sham group and model group in expression of TNF
      alpha, TGF-beta1, IL-6, Bax and Bcl-2 in the cartilage tissue. Myrtol
      significantly reduced the expression of TNF-alpha, IL-6 and Bax, and increased
      the expression of TGF-beta1 and Bcl-2 in myrtol group, comparing with those in
      model group (P < 0.01). CONCLUSIONS: Myrtol could down-regulate the expression of
      TNF-alpha, IL-6 and Bax, and up-regulate the expression of TGF-beta1 and Bcl-2.
      Myrtol standardized is a promising drug to ameliorate knee cartilage lesions in
      the OA rat model.

PMID- 25973030
TI  - MiRNA profile of osteosarcoma with CD117 and stro-1 expression: miR-1247
      functions as an onco-miRNA by targeting MAP3K9.
AB  - microRNAs (miRNA) are regulators of gene expression, but little is known about
      miRNA expression profiles in stem cells of osteosarcoma (OS). C117 and Stro-1 are
      known stem cell markers of OS. In the study, CD117 and stro-1 positive
      (CD117(+)stro-1(+)) and CD117 and stro-1 negative (CD117(-)stro-1(-)) cells were
      isolated from MG63 cells CD117(+)stro-1(+) cells showed more metastatic ability
      and stem cell formation rate than CD117(-)stro-1(-) ones. To find the difference
      between CD117(+)stro-1(+) and CD117(-)stro-1(-) cells, the miRNA expression
      profile was examined using DNA microarray. MicroRNAs were differentially
      expressed in osteosarcoma cells with CD117(+)stro-1(+) and CD117(-)stro-1(-). The
      significant miRNAs included miR-15a, miR-302a, miR-423-5p, miR-1247, miR-1243 and
      others, which were confirmed by real time RT-PCR. The significant down-regulated
      miR-1247 was confirmed that was a potential tumor suppressor by targeting MAP3K9.
      Our results indicated that dysregulation of miRNAs is involved in osteosarcoma
      and miR-1247 plays an important role in progression of osteosarcoma. 

PMID- 25973029
TI  - ACE2-Ang (1-7) axis is induced in pressure overloaded rat model.
AB  - ACE2-Ang (1-7) axis is a key regulator in cardiac hypertrophy, myocardial
      remodeling and development of heart failure. To investigate how ACE2-Ang (1-7)
      axis function in pressure-overload-induced heart failure, male SD rats (weighing
      about 250 g) were used to establish the model of pressure-overload-induced heart
      failure using aortic stenosis surgery. The level of plasma ACE2, ACE and Ang (1
      7) from heart failure group were significantly up-regulated compared with the
      sham group by ELISA test. The mRNA and protein expression of ACE2 in myocardial
      tissue from heart failure group also showed remarkably increased. Importantly, we
      found that the expression of ACE2 and Ang (1-7) were reversed in heart failure
      group after treatment with AT1 receptor antagonist telmisartan. Compared with
      heart failure group, the level of plasma ACE2, ACE and Ang (1-7) were
      significantly decreased in telmisartan treated group. The mRNA and protein
      expression of ACE2 in cardiac tissue from telmisartan group was also
      significantly decreased, while Mas mRNA and protein level was increased. Taken
      together, these studies demonstrated that the expression of ACE2-Ang (1-7) axis
      was induced in pressure-overload-induced heart failure model, suggesting that
      ACE2-Ang (1-7) axis may have a protective role in the development of heart
      failure and may provide a new target for drug development of heart failure. 

PMID- 25973031
TI  - High prevalence of maternal vitamin D deficiency in preterm births in northeast
      China, Shenyang.
AB  - INTRODUCTION: Maternal vitamin D deficiency has been associated with a number of
      fetal and neonatal health problems. Preterm birth is one of the most detrimental,
      and the role of maternal vitamin D deficiency in preterm births has not been
      universally acknowledged. There had been limited epidemiological studies of
      vitamin D deficiency on the Chinese population. SUBJECTS AND METHODS: 1103 women
      delivered in Shengjing Hospital, China Medical University from January 1(st),
      2012 to January 1(st), 2013. Finally, 821 mother-newborn pairs which contained
      143 mother-newborn pairs who were preterm delivery were recruited for analysis.
      RESULTS: There was significant difference between spring and summer (P<0.0001) as
      well as spring and autumn (P<0.01). Compared to those in summer and autumn, the
      25 (OH) D level was significantly lower in winter (summer vs winter P<0.0001,
      autumn vs winter P<0.0001). Maternal vitamin D level showed obvious variation
      with months and seasons, with higher level in summer months and lower level in
      winter months. There were significant difference between the vitamin D level of
      the very preterm group and the mildly preterm groups (P<0.01), as well as the
      very preterm group and the in-term groups (P<0.001). Prevalence of Vitamin D
      deficiency occurred in 63.04% of pregnant women in very preterm group, compared
      with 36.61% in in-term group. CONCLUSION: Vitamin D nutritional status of
      pregnant women and their newborns in Shenyang were relatively good compared to
      cities in similar latitudes. Vitamin D deficiency was most severe in late spring
      and least in summer. Severe preterm births before 31 weeks of gestation was
      associated with maternal vitamin D deficiency.

PMID- 25973032
TI  - Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC):
      clinical analyses of patients and an HCC rat model.
AB  - MicroRNAs (miRNAs) are associated with human carcinogenesis and tumor
      development. Moreover, serum miRNAs can reflect the level of tissue miRNAs and be
      potential tumor markers. Serum microRNA-21 (miR-21) is overexpressed in many
      human cancers including hepatocellular carcinoma (HCC). However, how serum miR-21
      changes during the HCC formation and whether miR-21 plays a regulatory role in
      this whole process are unknown. The current study evaluated the prognostic and
      diagnostic potential of serum miR-21 in HCC patients. Next, we established a HCC
      rat model and collected the blood and liver tissues at regular time points. AFP
      from the serum, RNA from the serum and liver tissues were collected and
      quantified separately. The results revealed that tissue and serum miR-21 was
      upregulated significantly in the groups of cirrhosis, early and advanced HCC
      compared with normal and fibrosis groups. The AFP levels were increased in early
      and advanced HCC compared with other groups. Then, the changes of miR-21
      downstream proteins (i.e., programmed cell death 4 [PDCD4] and phosphatase and
      tensin homolog [PTEN]) in the liver tissues were measured. PDCD4 and PTEN
      expression was decreased gradually after tumor induction and negatively
      correlated with miR-21 expression. All these results suggested that serum miR-21
      was associated with the prognosis of HCC; the changes in serum miR-21 were
      earlier and more accurately reflected the pathogenesis of HCC than AFP;
      therefore, it could be used as an early diagnostic marker for HCC. Our in vivo
      experiments further confirmed that miR-21 plays an important role in promoting
      the occurrence and development of HCC by regulating PDCD4 and PTEN. 

PMID- 25973033
TI  - Effect of rocuronium on the level and mode of pre-synaptic acetylcholine release
      by facial and somatic nerves, and changes following facial nerve injury in
      rabbits.
AB  - Muscles innervated by the facial nerve show differential sensitivities to muscle
      relaxants than muscles innervated by somatic nerves. The evoked electromyography
      (EEMG) response is also proportionally reduced after facial nerve injury. This
      forms the theoretical basis for proper utilization of muscle relaxants to balance
      EEMG monitoring and immobility under general anesthesia. (1) To observe the
      relationships between the level and mode of acetylcholine (ACh) release and the
      duration of facial nerve injury, and the influence of rocuronium in an in vitro
      rabbit model. (2) To explore the pre-synaptic mechanisms of discrepant responses
      to a muscle relaxant. Quantal and non-quantal ACh release were measured by using
      intracellular microelectrode recording in the orbicularis oris 1 to 42 days after
      graded facial nerve injury and in the gastrocnemius with/without rocuronium.
      Quantal ACh release was significantly decreased by rocuronium in the orbicularis
      oris and gastrocnemius, but significantly more so in gastrocnemius. Quantal
      release was reduced after facial nerve injury, which was significantly correlated
      with the severity of nerve injury in the absence but not in the presence of
      rocuronium. Non-quantal ACh release was reduced after facial nerve injury, with
      many relationships observed depending on the extent of the injury. The extent of
      inhibition of non-quantal release by rocuronium correlated with the grade of
      facial nerve injury. These findings may explain why EEMG amplitude might be
      diminished after acute facial nerve injury but relatively preserved after chronic
      injury and differential responses in sensitivity to rocuronium. 

PMID- 25973034
TI  - Are there differences between Sprague-Dawley and Wistar rats in long-term effects
      of ovariectomy as a model for postmenopausal osteoporosis?
AB  - Ovariectomized Sprague-Dawley (SD) and Wistar rats are widely used as animal
      models for postmenopausal osteoporosis. This study aimed to investigate
      differences in the long-term effects of ovariectomy on these two breeds of rats.
      6-month-old SD and Wistar rats underwent sham operation (Ssham and Wsham) or
      bilateral ovariectomy (Sovx and Wovx). Body weight, absolute fat, fifth and sixth
      lumber vertebrae (L5-6) bone mineral density (BMD), and whole body bone mineral
      content (BMC) were evaluated from 14 to 68 weeks after operation. Body weight
      significantly increased compared to shams at every point (except 68 weeks) for
      Sovx and at 14, 21 and 38 weeks for Wovx (all P < 0.05), the increases were not
      significantly different between breeds. Absolute fat increased significantly
      compared to shams at every point (except 14 and 68 weeks) for Sovx and at 30
      weeks for Wovx (all P < 0.05), the increases were significantly different between
      Sovx and Wovx (P = 0.007), but not the shams. L5-6 BMD increased then decreased
      and was significantly lower than shams at 30, 38 and 50 weeks for Sovx and at 14
      weeks for Wovx (all P < 0.05), the initial increases were significantly different
      between Sovx and Wovx (P = 0.006), but not the shams. BMC was significantly
      decreased compared to sham groups at every point (except 14 and 68 weeks) for
      Sovx and at 14, 21, 38, and 50 weeks for Wovx (all P < 0.05), the decreases were
      not significantly different between breeds. In conclusion, ovariectomy had a
      greater effect upon absolute fat and L5-6 BMD in SD rats.

PMID- 25973035
TI  - Relationship between osteopontin and beta-catenin immunohistochemical expression
      and prognostic parameters of colorectal carcinoma.
AB  - Previous studies on the prognostic value of osteopontin (OPN) and beta-catenin in
      colorectal carcinoma (CRC) revealed conflicting results. To date, only two
      immunohistochemical studies investigated their association in CRC with discrepant
      results. Moreover, the relevance of their co-expression to clinicopathological
      parameters was not previously reported. This study was designed to investigate
      the relationship between these markers and prognostic parameters in CRC and study
      further the relationship between them. Immunohistochemical expression of OPN and
      beta-catenin was evaluated in 72 CRCs. Cytoplasmic OPN was detected in 45.83% of
      CRCs while normal mucosa was immunonegative. Strong continuous membranous beta
      catenin was present in normal mucosa. However, abnormal membranous, nuclear and
      cytoplasmic expressions were observed in 36.11%, 31.94% and 52.78% of CRCs,
      respectively. A highly significant relationship was detected between each of OPN
      and nuclear beta-catenin expression and lymph node metastasis (P = 0.0001 and
      0.004 respectively), depth of invasion (P = 0.001 and 0.004 respectively), TNM
      stages (P = 0.0001 and 0.001 respectively) and Dukes' stages (P = 0.0001 and
      0.004 respectively). A significant association was found between OPN and distant
      metastases. A strong agreement was observed between OPN and nuclear beta-catenin
      (kappa = 0.656). A highly significant relationship was found between their co
      expression and poor prognostic parameters. OPN overexpression and nuclear beta
      catenin expression appeared to be associated with unfavorable prognostic factors
      in CRC. A direct relationship was observed between them. Further understanding
      their role in colorectal carcinogenesis as well as targeting the interaction
      between them might be effective in the future development of therapeutic agents
      for CRC patients. 

PMID- 25973036
TI  - Up-regulation of miR-877 induced by paclitaxel inhibits hepatocellular carcinoma
      cell proliferation though targeting FOXM1.
AB  - Paclitaxel is an effective chemotherapeutic agent for treatment of cancer
      patients, and frequently, clinical outcome is influenced by paclitaxel
      sensitivity. Despite this, our understanding of the molecular basis of paclitaxel
      response is incomplete. Recently, it has been shown that microRNAs (miRNAs)
      influence messenger RNA (mRNA) transcriptional control and can contribute to
      human carcinogenesis. In the present study, our objective was to identify miR-877
      associated with HCC cell lines response to paclitaxel and to evaluate these
      miRNAs as therapeutic targets to increase paclitaxel sensitivity. We measured the
      expression of miR-877 in paclitaxel-treated HCC cell lines. We verified that miR
      877 was up-regulated in paclitaxel-induced HCC cells by real-time PCR. We further
      investigated the role and mechanisms of miR-877. Over-expression of miR-877 in
      HCC cells partially restores paclitaxel sensitivity. The proliferation activity
      and the colony formation activity of HCC cells were both inhibited after
      transfected with miR-877. MiRNA targets prediction algorithms imply FOXM1 serves
      as a target gene for miR-877. A fluorescent reporter assay confirmed that miR-877
      binds specifically to the predicted site of the FOXM1 mRNA 3'-untranslated region
      (3'UTR). When miR-877 was overexpressed in HCC cells, the protein levels of FOXM1
      was downregulated. These results indicate that miR-877 could influence the
      sensitivity of paclitaxel treatment in hepatocellular carcinoma cell lines by
      targeting FOXM1. 

PMID- 25973037
TI  - The expression of marker for endometrial stem cell and fibrosis was increased in
      intrauterine adhesious.
AB  - OBJECTIVES: The objective of the present study was to evaluate whether fibrotic
      markers and endometrial stem cell markers were abnormal expressed in endometrium
      of intrauterine adhesions and a female mouse model for intrauterine adhesions.
      METHODS: We revaluated endometrial fibrosis using Masson's stain. We detected the
      expression of endometrium stem cell markers (CD146 and CD140b) and fibrosis
      markers (TGF-Beta, CTGF, collagen protein I and collagen protein III) in
      endometrial tissue with intrauterine adhesions using real-time PCR and S-P
      (Streptavidin-Peroxidase) immunohistochemistry. We create a female mouse model
      for intrauterine adhesions using mechanical injury, and then revalue the
      expression of endometrial stem cell markers and fibrosis markers in endometrial
      tissue of mouse model for intrauterine adhesions. RESULTS: The ratio of the area
      with endometrial fibrosis to total endometrial area in intrauterine adhesious
      significantly increased compared with the normal endometrial tissue (P < 0.05);
      The expression levels of fibrotic markers and endometrial stem cell markers were
      higher in the endometrial tissue with intrauterine adhesious compared to normal
      endometrial tissue (P < 0.05). The animal experiments showed that the ratio of
      the area with endometrial fibrosis to total endometrial area significantly
      increased compared with the control group (P < 0.05); The expression levels of
      fibrotic markers and endometrial stem cell markers were higher in the endometrial
      tissue compared to the control group (P < 0.05). CONCLUSION: Aberrant activation
      of fibrosis may be involved in the pathology of intrauterine adhesious.

PMID- 25973038
TI  - Identification of potential plasma biomarkers for esophageal squamous cell
      carcinoma by a proteomic method.
AB  - Among malignant tumors, the mortality rate of esophageal squamous cell carcinoma
      (ESCC) ranks sixth in the world. Late-stage diagnosis of ESCC increases the
      mortality. Therefore, more effective biomarkers for early diagnosis of ESCC are
      necessary. Unfortunately, appropriate biomarkers for clinical diagnosis and
      prognosis have not been identified yet. However, recent progresses in
      quantitative proteomics have offered opportunities to identify plasma proteins as
      biomarkers for ESCC. In the present study, plasma samples were analyzed by
      differential in-gel electrophoresis (DIGE) and differentially expressed proteins
      were identified by matrix assisted laser desorption ionization-time of
      flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). A total of 31
      proteins representing 12 unique gene products were identified, in which 16
      proteins were up-regulated and 15 down-regulated in tumors. The up-regulated
      proteins were alpha-2-HS-glycoprotein (AHSG), leucine-rich alpha-2-glycoprotein
      (LRG), zinc-alpha-2-glycoprotein, alpha-1-antichymotrypsin, complement factor I
      and complement C4-B, whereas the down-regulated proteins were serum albumin, Ig
      alpha-2 chain C region, alpha-1-antitrypsin, fibrinogen gamma chain, haptoglobin
      and hemoglobin subunit alpha. Among all the differentially expressed proteins,
      AHSG and LRG were validated by ELISA. The results were consistent with the data
      from the proteomics results, further suggesting that AHSG and LRG may be employed
      as potential biomarkers for the early diagnosis of ESCC. In summary, this study
      was the first time to use DIGE combined MALDI-TOF/TOF platform to identify the
      potential plasma biomarkers for ESCC. The plasma AHSG and LRG showed great
      potential for ESCC screening. 

PMID- 25973039
TI  - Role of miR-101 in pheochromocytoma patients with SDHD mutation.
AB  - This study aimed to screen the potential diagnostic biomarkers for distinguishing
      the malignant pheochromocytoma (PCC) from benign PCC. A total of 59 patients with
      PCC (benign and malignant) were enrolled in this study. The expression level of
      miRNAs in patients with different kind PCCs (healthy control, benign, malignant,
      malignant with or without SDHD mutation, adrenal and extra-adrenal) was analyzed
      using the qRT-PCR analysis. Besides, the diagnosis accuracy of miRNA in PCC
      samples was analyzed using the ROC analysis. Moreover, level of miR-101 in serum
      was detected by qRT-PCR analysis and serum VEGF level in patients with PCC was
      detected using the ELISA kit. Compared with benign PCC, miR-101 level was higher
      in patients with malignant PCC (P < 0.05), while the level of miR-513-5p and miR
      26b showed no difference between malignant PCC and benign PCC (P > 0.05). miR-101
      expression was significantly increased in malignant tumor tissue with SDHD
      mutation (P < 0.05) and in extra-adrenal tissues (P < 0.05), respectively.
      Besides, AUCs for miR-101 in PCC samples was 0.79 and for which in PCC samples
      with non-SDHD mutation was 0.77. Besides, serum miR-101 in malignant PCC was high
      but showed no difference among groups (P > 0.05). Moreover, serum VEGF level in
      malignant tumors was significantly high compared with benign tumor, as well as
      that in malignant PCC with SDHD mutation (P < 0.05). Our study suggested that
      SDHD mutation may enhance the overexpression of miR-101 in malignant tumors and
      miR-101 may be a potential diagnostic biomarker for malignant PCC and benign PCC.

PMID- 25973040
TI  - Continuous hemodiafiltration therapy reduces damage of multi-organs by
      ameliorating of HMGB1/TLR4/NFkappaB in a dog sepsis model.
AB  - In the present study, we investigated whether CVVH can reduce HMGB1, TLR4, NF
      kappaB and other serum cytokine levels, preventing organ injury in a dog sepsis
      model. A total of 10 dogs were injected with LPS and treated with either CVVH
      group (n = 5) or nothing (Control, n = 5) for 24 h. EILSA was used for examining
      the concentration of TNF-alpha, IL-6, HMGB 1 and TLR4. The histological change of
      lung, liver and kidney tissues was determined. The mRNA expression of HMGB1, TLR4
      and NF-kappaB was examined by RT-PCR. The protein of HMGB1 and phosphated NF
      kappaB was examined by Western-blot. The levels of serum HMGB1 came to the peak
      at 8 h, 16 h and then declined. The LPS-induced increase in HMGB1 level was
      suppressed by CVVH compared with Control. Likewise, serum TNF-alpha and IL-6
      levels decreased with CVVH along with a significant improvement in the function
      of main organs. Histologic examination revealed significant reduction in
      inflammation in lung; liver and kidney tissues harvested 24 h after CVVH compared
      with Control. The mRNA of HMGB1, TLR4 and NF-kappaB in the kidney was expressed
      at high level after LPS administration, which was significantly decreased by
      CVVH. The increased protein expression of HMGB1 and phosphated NF-kappaB was
      reduced after CVVH compared with control. CVVH by reducing the level of HMGB1,
      TLR4, NF-kappaB and other cytokines could weaken the cascade of cytokines and
      restore the immune system, and reduce the damage of important organs in sepsis. 

PMID- 25973042
TI  - Cullin-1 promotes cell proliferation via cell cycle regulation and is a novel in
      prostate cancer.
AB  - BACKGROUND: There is no reliable marker available for early detection, diagnostic
      confirmation, or disease prognosis available of prostate cancer (PCa). We aimed
      to evaluate the function of Cullin-1 and unravel its underlying molecular
      mechanism to develop novel treatment options equivalent to PCa. METHOD: We used
      immunohistochemistry to analyze the correlation between Cullin-1 expression and
      clinicopathologic variables and patient survival. The Cullin-1 level was tested
      in PCa cells. The role of regulation of Cullin-1 in PCa was applied in vitro and
      vivo. In addition, we further investigated the signaling pathway of Cullin-1 in
      prostate cancer cell proliferation. RESULT: We first discovered that Cullin-1
      expression was upregulated in human PCa tissues and inversely related with PCa
      differentiation. We then found that high expression of Cullin-1 protein suggested
      a poor prognosis in PCa patients. Also, Cullin-1 promotes PCa cell proliferation
      in vitro and tumor growth in vivo. We then found that the mechanism of Cullin-1
      regulation on cell-cycle progression is due to increased expression of p21 and
      p27, and decreased expression of cyclin D1 and cyclin E after Cullin-1 knockdown.
      CONCLUSION: Cullin-1 exerts multiple biological effects in the PCa cell line.
      Through promoting proliferation and by countering cisplatin-induced apoptosis,
      Cullin-1 has been deeply implicated in the pathogenesis and development of PCa.

PMID- 25973041
TI  - Downregulated miR-29c correlates with increased BACE1 expression in sporadic
      Alzheimer's disease.
AB  - BACKGROUND: Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is
      conceived as a potential target for therapies against Alzheimer disease (AD)
      which is characterized by the accumulation of plaques formed of short beta
      amyloid (APPbeta) peptides. Recently, such microRNAs, as miR-29a, miR-29b-1 have
      been shown to correlate with abnormally high levels of BACE1 and APPbeta in
      sporadic AD. METHODS: In order to confirm whether miR-29c correlates with the
      BACE1 upregulation in sporadic AD, we firstly evaluated the expression of miR-29c
      and BACE1, the APPbeta accumulation in sporadic AD brain tissues and analyzed the
      correlation of miR-29c with BACE1. Then we determined the regulation of miR-29c
      in human heuroblastoma SH-SY5Y cells on the BACE1 expression and APPbeta
      accumulation. And finally we determined the targeting to 3' UTR of BACE1 by miR
      29c by a luciferase reporter. RESULTS: It was demonstrated that miR-29c was
      downregulated in sporadic AD brains, in an association with an upregulation of
      BACE1 in both mRNA and protein level of BACE1, and also an elevated APPbeta
      accumulation. And the manipulated high level of miR-29c with miR-29c mimics
      transfection significantly reduced the protein level of BACE1 and APPbeta
      accumulation in human neuroblastoma SH-SY5Y cells. Further luciferase reporter
      assay demonstrated that miR-29c targets the 3' UTR of BACE1 and downregulated the
      BACE1 in HEK293 cells. CONCLUSION: Present study indicated that miR-29c was
      downregulated in sporadic AD brains, and it targeted the 3' UTR of BACE1, reduced
      the BACE1 expression, and downregulated the APPbeta accumulation in vitro.

PMID- 25973043
TI  - Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling
      pathway in vitro.
AB  - Breast cancer bone metastases are attributed to multiple cellular and molecular
      interactions between the cancer cells and the bone microenvironment. Some breast
      cancers (about 10%) manifest predominant osteoblastic bone metastases. However,
      the effects of cancer cell-produced factors on osteoblastic differentiation are
      not fully understood. Semaphorin 3A (Sema 3A) is a newly identified regulatory
      factor of bone rebuilding. In the present study, we demonstrated that human
      breast cancer MCF-7 cells, which preferentially form osteoblastic bone
      metastases, exhibited increased Sema 3A expression levels. We also found that MCF
      7 cell-derived Sema 3A stimulated osteoblastic differentiation and nuclear beta
      catenin accumulation, and these effects could be blocked by shRNA Sema 3A or a
      Sema 3A-neutralizing antibody. In conclusion, our data suggest that MCF-7 cell
      derived Sema 3A plays a causative role in osteoblastic bone metastases
      progression by stimulating osteoblastic differentiation. 

PMID- 25973044
TI  - Expression of IL-4 and IL-13 predicts recurrence and survival in localized clear
      cell renal cell carcinoma.
AB  - Interleukin-4 (IL-4) and IL-13 are anti-inflammatory and immunoregulatory
      cytokines that can influence cancer-directed immunosurveillance. However, they
      are not evaluated as biomarkers for ccRCC outcomes. The aim of this study was to
      investigate the prognostic value of tumor-derived IL-4 and IL-13 in patients with
      localized ccRCC after surgery. Our study comprised 194 consecutive patients with
      localized ccRCC undergoing nephrectomy in a single center. Clinical
      characteristics, recurrence-free survival (RFS) and overall survival (OS) were
      recorded. We assessed IL-4 and IL-13 expression as continuous variables and
      dichotomized as low versus high by immunohistochemistry. For associations with
      RFS and OS, we used the Kaplan-Meier method and Cox regression models.
      Concordance index was calculated for predictive accuracy. We found that high
      expression levels of IL-4 and IL-13 were associated with increased recurrence (P
      < 0.001 and P = 0.006, respectively) and reduced survival (P = 0.001 and P =
      0.016, respectively). Furthermore, multivariate analyses confirmed that
      combination of IL-4 and IL-13 expression (IL-4/IL-13 signature) was an
      independent prognostic factor for RFS and OS (P = 0.009 and P = 0.016,
      respectively). When applied to UISS score, IL-4/IL-13 signature improved the
      predictive accuracy. Notably, this improvement in prediction was mainly observed
      in patients with low-risk disease. To conclude, IL-4/IL-13 signature is an
      independent predictor of outcomes in patients with localized ccRCC, and the
      prognostic value is more prominent among patients with low-risk disease.
      Evaluation of IL-4 and IL-13 expression provides the opportunity to optimize
      postsurgical management and develop novel targeted therapies for ccRCC patients. 

PMID- 25973045
TI  - Local bone interaction between renin-angiotensin system and kallikrein-kinin
      system in diabetic rat.
AB  - OBJECTIVE: This study was performed to investigate bone deteriorations and the
      involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin
      system (KKS) of male rat in response to the hyperglycemia. METHODS: The
      biomarkers in serum and urine were measured by ELISA kit, and tibias were taken
      for the measurement on gene, protein expression and histological analysis, femurs
      were taken for the measurement on biomechanical parameters and micro-CT. RESULTS:
      The DM1 showed the decreased level of osteocalcin, testosterone and FGF-23, and
      the increased level of serum CTX as compared to those of vehicle group. The H&E
      staining showed remarkable bone deteriorations, including increased
      disconnections and separation of trabecular bone among growth plate and joint
      cartilage in DM1 group. Biomechanically, the maximum load, maximum stress, and
      strain parameter of DM1 group was significantly lower than control group. Type 1
      diabetic mice displayed bone loss shown the reduction of bone volume/total
      volume, trabecular number, trabecular thickness and bone mineral density. The STZ
      injection significantly up-regulated mRNA expression of AT1R, AGT, renin, renin
      receptor, and ACE, and the expression of AT2R, B1R and B2R were down-regulated in
      tibia of rat in hyperglycemia group. The protein expression of renin, ACE and Ang
      II were significantly up-regulated, and AT2R, B1R and B2R were down-regulated in
      DM1 group. CONCLUSIONS: The treatment of hyperglycemia was detrimental to bone as
      compared to the vehicle group, and the underlying mechanism was mediated, at
      least partially, through down-regulation of KSS activity and up-regulation of RAS
      activity in local bone.

PMID- 25973046
TI  - CD317 is over-expressed in B-cell chronic lymphocytic leukemia, but not B-cell
      acute lymphoblastic leukemia.
AB  - CD317 was first identified as a multiple myeloma-associated antigen. Here we
      report the expression of CD317 in normal B cells and B-cell malignancies. In
      normal bone marrow, CD317 demonstrates a biphasic expression pattern, with higher
      expression on stage 1 and stage 3 hematogones, but not on stage 2 hematogones.
      CD317 is over-expressed in B-cell chronic lymphocytic leukemia, and appears
      associated with negative CD38 expression. Moreover, CD317 is barely detectable in
      B-cell acute lymphoblastic leukemia. Our results suggest that CD317 expression
      might be of prognostic significance for B-CLL, and CD317 could be used as a new
      marker for minimal residual disease detection in B-ALL. 

PMID- 25973047
TI  - ClC-3 chloride channel modulates the proliferation and migration of osteosarcoma
      cells via AKT/GSK3beta signaling pathway.
AB  - In cultured human osteosarcoma (OS) cells, we recently demonstrated that insulin
      like growth factors (IGF-1)-induced MG-63 and 143B human OS cells proliferation
      were consistent with increasing ClC-3 expression, and ClC-3 was up-regulated in
      cells with high metastatic potency. Blockade of ClC-3 greatly suppressed the
      phosphorylation activation of Akt/GSK3beta. We also found that blockade of ClC-3
      effectively down-regulated the expression of cyclin D1 and cyclin E, and caused
      activation of p27(KIP) and p21(CIP). The synthesized effects on these proteins
      which play a major role in cell cycle regulation bring about G0/G1 cell cycle
      arrest in MG-63 cells, and finally abrogate the cell proliferation. Besides, ClC
      3 deletion attenuates OS cell migration via down-regulation the expression of MMP
      2 and MMP-9. Such information suggests that ClC-3 might be a potential target for
      anti-OS. 

PMID- 25973048
TI  - Expression of S100 family proteins in neonatal rats with sepsis and its
      significance.
AB  - OBJECTIVE: This study aims to study the expression changes of S100 family
      proteins in neonatal rats with sepsis and investigate the effect and significance
      of S100 family proteins in pathogenesis and development of sepsis. METHODS: The
      functions of S100 family proteins were analyzed with bioinformatics. The immune
      associated proteins were chosen as the candidate proteins. Twenty neonatal SPF SD
      rats were randomly divided into two groups: sepsis model group and control group.
      The liver sample was stained with HE to evaluate the establishment of sepsis
      model. The expression amount of proinflammatory factor IL-1, IL-6 and TNF-alpha
      was detected with ELISA. The expression changes of S100A8, S100A9, S100A11 and
      S100A12 in sepsis model rats were detected with real-time PCR and Western
      blotting. After shRNA plasmid was transfected into THP-1 cells and the expression
      of S100A12 was silenced, the expression changes of proinflammatory factor IL-1,
      IL-6 and TNF-alpha in LPS-induced inflammation were studied in order to
      investigate the S100A12 mediated inflammatory process. RESULTS: IL-1, IL-6 and
      TNF-alpha in the serum of rats with sepsis induced by LPS were 55.79 +/- 3.80
      ng/l, 48.76 +/- 1.03 ng/l and 29.98 +/- 2.27 ng/l respectively. S100A8, S100A9,
      S100A11 and S100A12 detected with real-time PCR in sepsis model group were 14.4
      +/- 1.37, 10.23 +/- 1.81, 5.5 +/- 1.64 and 9.97 +/- 1.82 respectively. Compared
      with the control group, S100A8, S100A9, and S100A12 were significantly up
      regulated. The shRNA silenced the expression of S100A12 which reduced the
      expression of proinflammatory factors after LPS stimulated the cells (P < 0.05).
      CONCLUSION: Compared with the control group, S100A8, S100A9, and S100A12 were
      significantly up-regulated in rat sepsis model group. After the expression of
      S100A12 in propylene glycol monomethyl ether acetate (PMA) induced human
      macrophages was silenced, the expression of proinflammatory factor IL-1, IL-6 and
      TNF-alpha was down-regulated.

PMID- 25973049
TI  - Isolation and phenotypic characteristics of microparticles in acute respiratory
      distress syndrome.
AB  - OBJECTIVE: To investigate the alterations of microparticles in acute respiratory
      distress syndrome (ARDS) in rats. METHODS: 18 Wistar male rats were randomly
      divided into three groups: no intervention, sham (saline control) group and ARDS
      group (LPS induced). Blood was collected from abdominal aorta and microparticles
      were extracted through multiple rounds of centrifugation. Particles were analyzed
      by flow cytometry and transmission electron microscope. RESULTS: The circulating
      concentration of total microparticles of rats with ARDS induced by
      lipopolysaccharide (LPS) did not change compared with other two groups. However,
      ARDS rats expressed higher concentration of leukocyte- and endothelium- derived
      microparticles in the three groups. CONCLUSION: Our results indicate that
      leukocyte and endothelial cell-derived particles may play an important role in
      ARDS. Thus it is important not only to monitor total microparticle levels but
      also the phenotypes, which may contribute to the prevention and early treatment
      of ARDS.

PMID- 25973050
TI  - Holoturia arenicola extract modulates bile duct ligation-induced oxidative stress
      in rat kidney.
AB  - BACKGROUND: Acute Renal Failure (ARF) in patients with cirrhosis is one of the
      most frequently encountered complications of obstructive jaundice. Marine
      organisms from the Mediterranean Coast of Egypt are considered potential sources
      of bioactive molecules. The present study was undertaken to explore the curative
      effects of Holothuria arenicola extract (HaE) against renal injury induced by
      bile duct ligation in male albino rats. METHODS: Fifty four male Wistar albino
      rats were assigned into two main groups, the Sham-operated control (received
      distilled water only for 28 days) and bile duct ligated (BDL) group, which
      divided into 2 subgroups, animals of these subgroups treated for 28 consecutive
      days as follow: Subgroup I (BDL), rats of this subgroup administered distilled
      water orally. Subgroup II, animals of this subgroup treated orally with HaE (200
      mg/kg body weight). RESULTS: BDL induced marked alteration on renal functions as
      manifested by a significant increase in the kidney function markers, serum
      creatinine, urea and uric acid. In addition, BDL caused significant increase in
      MDA level and significant decrease in GSH level as well as antioxidant enzymes
      activities (GST, SOD and CAT). However, administration of HaE for consecutive 28
      days significantly reversed these changes, suggesting that the renal curative
      effect of HaE against oxidative stress- induced injury might be involved in
      decreasing lipid peroxide generation and stimulating antioxidant status.
      CONCLUSION: The present study revealed that HaE had a profound effect against BDL
      induced oxidative stress in the kidney tissues which is the common feature of
      choestasis in the liver.

PMID- 25973051
TI  - Kank1 reexpression induced by 5-Aza-2'-deoxycytidine suppresses nasopharyngeal
      carcinoma cell proliferation and promotes apoptosis.
AB  - Kank1, which was first described as a potential tumor suppressor for renal cell
      carcinoma (RCC), mapped to 9p24.3 and encoded an ankyrin-repeat domain-containing
      protein. Its frequent deletion was found to be associated with several human
      malignant tumors, cerebral palsy, and neuronal and developmental diseases.
      However, its functional role in nasopharyngeal cancer (NPC) was still unknown. In
      the present study, we found that Kank1 expression was down-regulated in NPC cells
      than in human nasopharyngeal epithelial cell line NP69 and demethylating agent 5
      aza-2'-deoxycytidine (5-aza-CdR) could improve its mRNA and protein expression
      level. Further studies demonstrated that DNA methylation might be the mainly
      cause for Kank1 decreased expression and restored Kank1 expression mediated by 5
      aza-CdR played a key role in suppressing NPC cells growth and inducing its
      apoptosis. Our primary results revealed new function of Kank1 for NPC and implied
      that epigenetic regulation especially demethylation may have a potential value
      for NPC treatment. 

PMID- 25973052
TI  - Synergistic effects of AKAP95, Cyclin D1, Cyclin E1, and Cx43 in the development
      of rectal cancer.
AB  - OBJECTIVE: To explore the expression of A-kinase anchor protein 95 (AKAP95),
      Cyclin D1, Cyclin E1, and Connexin43 (Cx43) in rectal cancer tissues and assess
      the associations between each of the proteins and pathological parameters, as
      well as their inter-relationships. METHODS: AKAP95, Cyclin D1, Cyclin E1, and
      Cx43 protein expression rates were evaluated by immunohistochemistry in 50 rectal
      cancer specimens and 16 pericarcinoma tissues. RESULTS: The positive rates of
      AKAP95, Cyclin E1, and Cyclin D1 proteins were 54.00 vs. 18.75%, 62.00 vs. 6.25%,
      and 72.00 vs. 31.25% in rectal cancer specimens and pericarcinoma tissues,
      respectively, representing statistically significant differences (P < 0.05). The
      positive rate of Cx43 protein expression in rectal cancer tissues was 44.00% and
      62.50% in pericarcinoma tissues, and the difference between them was not
      significant (P > 0.05). No significant associations were found between protein
      expression of AKAP95, Cyclin E1, Cyclin D1, and Cx43, and the degree of
      differentiation, histological type, and lymph node metastasis of rectal cancer (P
      > 0.05). However, significant correlations were obtained between the expression
      rates of AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43
      protein, and Cyclin D1 and Cx43, respectively (P < 0.05). CONCLUSION: AKAP95,
      Cyclin E1, and Cyclin D1 protein expression rates were significantly higher in
      rectal cancer tissues compared with pericarcinoma samples, suggesting an
      association between these proteins and the development and progression of rectal
      cancer. In addition, the significant correlations between the proteins (AKAP95
      and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1
      and Cx43) indicate the possible synergistic effects of these factors in the
      development and progression of rectal cancer.

PMID- 25973053
TI  - Assessing methylation status of PAX1 in cervical scrapings, as a novel diagnostic
      and predictive biomarker, was closely related to screen cervical cancer.
AB  - OBJECTIVE: Previous studies have demonstrated that levels of hypermethylation of
      paired boxed gene 1 in cervical tissues are associated with the grades of
      severities of cervical neoplasia in women, which suggests that testing for DNA
      methylation has a potential role in neoplasma screening. In this study, by
      testing methylation levels of PAX1 genes in cervical scrapings and cervical
      tissues of different lesion levels, aims to evaluate the diagnostic value of DNA
      methylation testing as a biomarker for early detecting cancerous changes in
      cervical tissues and to compare the efficacy between PAX1 methylation test and
      HPV test in detecting of cervical cancer. METHODS: A total of 121 cervical
      scrapings were analyzed, including normal (n = 28), cervical intraepithelial
      neoplasm 1 (CIN1; n = 32), CIN2/3 (n = 34), and invasive cancer (n = 27), which
      were all diagnosed by pathologic examination. RESULTS: The values of PAX1
      methylation reference in invasive cancer (mean [SE], 26.3 [3.5]) was
      significantly higher than CIN2/3 (13. 2 [2.2]) and the CIN1 (4.5 [0.45]; P <
      0.001). The PAX1 promoter was hypermethylated in 100% of invasive cancer tissue
      compared with 0% of normal tissue, 9% of CIN1, 44% of CIN2/3 (P < 0.01).
      Methylation levels of cervical scrapings and cervical tissues represent strong
      consistency within each group. In contrast, the HPV test result was positive in
      17% of normal tissue, 81% of CIN1, 91% of CIN2/CIN3, and 92% of invasive cancer.
      Based on receiver operating characteristic (ROC) analysis, hypermethylation of
      PAX1 was a significant candidate in segregating cervical cancer from
      normal/cervical neoplasia cases (P < 0.001). At an optimal cutoff value,
      sensitivity and specificity between 80% and 93% were obtained. In conclusion, the
      current results indicated that the methylation density of PAX1 by pyrosequencing
      in cervical scrapings held a great promise for cervical cancer screening.

PMID- 25973054
TI  - Increased HDAC3 and decreased miRNA-130a expression in PBMCs through recruitment
      HDAC3 in patients with spinal cord injuries.
AB  - The study was performed to investigate the molecular mechanism for SCI patients.
      The interaction between miRNA-130a and HDAC was demonstrated in PBMCs from SCI
      patients. Increased HDAC3 and decreased miRNA-130a were observed in PBMCs from AS
      patients. Next, HDAC3 loss-of-function or HAAC3 inhibition promoted the
      expression of miRNA-130a, and HDAC3 could be recruited to the promoter region of
      the gene, miRNA-130a, in PBMCs. In addition, linear regression analysis indicated
      that mRNA expression results were highly negative correlated between HDAC3 and
      miRNA-130a in PBMCs from SCI patients. Furthermore, miRNA-130a down expression
      increased the expression of HDAC3 in PBMCs. Loss-of-function of miRNA-130a
      promoted PBMCs apoptosis, but HDAC3 loss-of-function had no significant effect on
      the apoptotic cell. In addition, miR-130a overexpression decreased, whereas miR
      130a inhibition increased, the expression of TNF-alpha in PBMCs. Furthermore,
      HDAC3 loss-of-function or HAAC3 inhibition associated with simultaneous up
      regulation the expression of miR-130a and down-regulation the expression of TNF
      alpha in PBMCs. In conclusion, HDAC3 regulated a distinct underlying molecular
      and pathogenic mechanism of SCI by forming a negative feedback loop with miR-130a
      and enhanced TNF-1alpha expression. 

PMID- 25973055
TI  - LATS2-mediated YAP1 phosphorylation is involved in HCC tumorigenesis.
AB  - YAP (yes-associated protein) is a transcriptional co-activator that acts
      downstream of the Hippo signaling pathway and regulates multiple cellular
      processes, including proliferation and apoptosis. Although YAP plays an important
      role in various tumors, the underlying mechanism in hepatocellular carcinoma
      (HCC) tumorigenesis remains unclear. In this study, we observed that the LATS2
      was highly expressed in Bel-7402 and HepG2 cell lines, and LATS2 protein level
      was negatively correlated with YAP1 in HCC cells. And then, we inhibited LATS2
      expression by transfecting with siRNA. Western blot and Immunofluorescent
      staining analysis demonstrated that LATS2 inhibition decreased the
      dephosphorylation of YAP1 protein and promoted YAP1 nuclear accumulation in HCC
      cells. Moreover, Immunoprecipitation assay results also indicated that Yap binds
      directly to TEAD2 and LATS2 inhibition-mediated dephosphorylation increased the
      YAP1/TEAD2 association, leading to YAP1/TEAD2 transcriptional activation, which
      in turn upregulated cell invasion in HCC cells. Taken together, our current data
      indicated a new regulatory mechanism of YAP1 by the LATS2-mediated
      phosphorylation that was involved in HCC tumorigenesis. 

PMID- 25973056
TI  - SOX14 promotes proliferation and invasion of cervical cancer cells through
      Wnt/beta-catenin pathway.
AB  - SOX14 is a member of the SOXB2 subgroup of transcription factors implicated in
      neural development. Although SOX14 expression profile and function during
      development was revealed in various animal model systems, the role of this gene
      during tumor progression is totally unknown. In this study, the expression of
      SOX14 increases in four cervical cancer cell lines (HeLa, Caski, HT-3 and SiHa)
      as revealed by real-time PCR and Western blot analyses. Through knocking down or
      overexpressing SOX14 in SiHa and HeLa cells, the expression level of SOX14 was
      found to be positively related to cell proliferation and invasion in vitro.
      Moreover, the TOP-Flash reporter assay and Western blot for beta-catenin genes of
      the Wnt/beta-catenin pathway, indicated that SOX14 significantly activated
      Wnt/beta-catenin signaling. Further study showed that the blockage of Wnt/beta
      catenin pathway by knocking down beta-catenin resulted in a significant
      inhibition of cell proliferation and invasion capacity induced by SOX14. To
      summarize, these results demonstrate that SOX14 can promote proliferation and
      invasion capacity of cervical cancer cells by activating the Wnt/beta-catenin
      pathway. 

PMID- 25973057
TI  - Prognostic significance and anti-proliferation effect of microRNA-365 in
      hepatocellular carcinoma.
AB  - MircroRNA functions as tumor suppressor or promoter in hepatocellular carcinoma
      (HCC). Researchers have found that miR-365 expression was lower in HCC tissues
      compared with that in adjacent normal tissues. However, its prognostic
      significance and anti-proliferation effect in HCC remain to be clarified. In this
      study, we firstly found that miR-365 expression was lower in HCC tissues compared
      with that in adjacent normal tissues. Then, we analyzed miR-365 expression level
      and its clinicopathological and prognostic significance. Finally, overexpression
      of miR-365 inhibits HCC cell proliferation and migration in vitro. Our findings
      suggest that miR-365 expression was an independent poor prognostic factor for HCC
      patient overall survival and suppressed tumor cell growth. Therefore, miR-365 may
      serve as a valuable prognostic marker and promising target for HCC. 

PMID- 25973058
TI  - Structural changes in the progression of atrial fibrillation: potential role of
      glycogen and fibrosis as perpetuating factors.
AB  - BACKGROUND: Previous studies of the goat heart subjected to prolonged atrial
      pacing induced sustained atrial fibrillation (AF). Structural changes included
      marked accumulation of glycogen in atrial myocytes. AIMS: In the present study,
      we hypothesized that glycogen deposition in canine atrial myocytes promotes
      paroxysmal forms of AF and is involved in fibrosis development in the later
      stages of AF. MATERIAL & METHODS: In dogs under pentobarbital anesthesia, tissues
      were obtained from the right and left atrial appendages (LAA/RAA). Periodic acid
      Schiff (PAS) and Masson's trichrome staining of the LAA/RAA from normal dogs, and
      those subjected to atrial pacing induced AF for 48 h or 8 weeks determined
      glycogen and collagen concentrations, respectively, using morphometric analysis.
      RESULTS: At baseline, there was a significant greater concentration of glycogen
      in the LAA than the RAA (P <= 0.05). Compared to the RAA, the LAA glycogen, was
      dense and locked against the intercalated discs. After pacing induced AF for 48
      hours and 8 weeks there was a marked increase in glycogen deposition,
      significantly greater than in the baseline state (P <= 0.05). There was a similar
      and progressive increase in collagen concentrations in each group (P <= 0.05).
      CONCLUSIONS: The differential in glycogen concentration, in conjunction with
      other factors, neural and electrophysiological, provide a basis for the greater
      propensity of the left atrium for paroxysmal AF, at baseline and 48 hours of
      pacing induced AF. The marked increase in collagen at 8 weeks of pacing provides
      a substrate for sustained AF. Evidence is presented linking glycogen accumulation
      and fibrosis as factors in the persistent forms of AF.

PMID- 25973059
TI  - BN52021 protects rat cardiomyocyte from doxorubicin induced cardiotoxicity.
AB  - The aim of this study was to assess the role of platelet activating factor (PAF)
      antagonist BN52021 in doxorubicin induced cardiotoxicity and to explore the
      mechanisms. H9c2 cardiomyocytes were employed to investigate the effect of
      BN52021 on doxorubicin induced cell viability and cell apoptosis. Signaling
      pathway of caspase 3, cytochrome c, calcium and p38 mitogen-activated protein
      (MAPK) was determined during the doxorubicin induced apoptosis. Our results
      showed BN52021 pretreatment could protected cell death induced by doxorubicin in
      H9c2 cardiomyocytes. Decrease concentration of [Ca(2+)] and expression of
      phosphorylated P38 MAPK were accounted for the protection effect. Inhibition of
      signaling pathway of calcium and p38 MAPK showed similar effect exerted by
      BN52021 in doxorubicin induced cell apoptosis. Our results demonstrated BN52021
      protected against doxorubicin induced cell death in H9c2 cardiomyocytes by
      calcium and p38 MAPK signaling in vitro. These finding may give insight on the
      treatment of doxorubicin induced cardiomyopathy. 

PMID- 25973060
TI  - Effects of NF-kappaB and hypoxia on the biological behavior of Y79 retinoblastoma
      cells.
AB  - We aimed to investigate the influence of nuclear factor-kappaB (NF-kappaB) on the
      biological behavior of Y79 retinoblastoma cells exposed to hypoxia and its
      possible mechanism. The cells were administrated with hypoxia, and/or 5 MUM
      pyrrolidine dithiocarbamate (PDTC) (a selective NF-kappaB inhibitor) to inhibit
      the NF-kappaB activity, expressions of NF-kappaB was measured by western blot,
      and the translocation of NF-kappaB was detected. To examine the proliferation of
      Y79 cells, MTT assay was applied. Transwell assay was used to detect the invasion
      and migration ability of cells. The expressions of molecules involved in invasion
      was analyzed including HIF-1alpha, MMP-2, 9, and VEGF. We found that hypoxia
      significantly activated NF-kappaB activity. While once the NF-kappaB was
      inhibited, the proliferation, invasion and migration ability of Y79 cells were
      also blocked. Interestingly, the expressions of invasion-involved molecules
      elevated by hypoxia induction were also decreased when NF-kappaB was inhibited.
      Hypoxia could significantly change the adhesive and invasive ability of Y79
      retinoblastoma cells, NF-kappaB signal might be one of the main mediators for
      these hypoxia induced cell changes of biological behavior via downregulation of
      HIF-1alpha and the invasion related molecules, and the mechanism still needs
      further investigation. 

PMID- 25973062
TI  - Anti-tumor effect and mechanism of cyclooxygenase-2 inhibitor through matrix
      metalloproteinase 14 pathway in PANC-1 cells.
AB  - OBJECTIVE: To investigate whether celecoxib, a selective cyclooxygenase-2 (COX-2)
      inhibitor, can attenuate proliferation, migration, invasion and MMP-14 expression
      in pancreatic cancer cells PANC-1 and the possible anti-tumor mechanism of
      celecoxib. METHODS: Human pancreatic cancer cell line PANC-1 cells were treated
      with diverse concentrations of celecoxib (20, 60, 100 MUmol/L). Cell
      proliferation, invasion and migration capabilities were measured by MTT
      colorimetry, transwell invasion assay, and scratch assay separately. At the same
      time, the protein expression of COX-2 and MMP-14 was assessed by ELISA. RESULTS:
      The capabilities of proliferation, invasion and migration in PANC-1 cells were
      attenuated in a concentration-dependent manner after treated with celecoxib,
      followed by the down-regulation of the protein expression of COX-2 and MMP-14. In
      addition, MMP-14 expression was significantly positively correlated with COX-2
      expression. CONCLUSIONS: COX-2 inhibitor celecoxib can inhibit the proliferation,
      invasion and migration of PANC-1 cells via down-regulating the expression of MMP
      14 in a concentration-dependent manner, thus contributing to its anti-tumor
      effect in pancreatic cancer.

PMID- 25973061
TI  - Downregulation of survivin inhibits proliferation and migration of human gastric
      carcinoma cells.
AB  - Gastric cancer is the second leading cause of cancer-related death worldwide.
      Survivin overexpressed in many human cancers as a member of the inhibitor of
      apoptosis protein family. We found that all samples of normal gastric tissues did
      not express the protein of survivin, and however, 65% human gastric cancer
      samples expressed survivin. Positive expression of survivin correlated with
      differentiation. The proliferation and migration of gastric cancer decreased
      after downregulation of surviving by RNA interference. Furthermore,
      downregulation of survivin caused the cell cycle arrest. These suggest that
      survivin play an important role in gastric cancer and the use of survivin siRNA
      might become an effective approach to cancer therapy. 

PMID- 25973063
TI  - Modulation of the function of dendritic cells in adolescents with chronic HBV
      infection by IFN-lambda1.
AB  - The exact immunology pathogenesis of hepatitis B virus (HBV) infection remains
      unclear currently. The dendritic cells (DCs) dysfunction is evident in
      adolescents with chronic HBV infection in the immune tolerant phase. DCs, as the
      most efficient professional antigen-presenting cells (APCs), possess the
      strongest antigen presenting the effect in the body and can stimulate the initial
      T cell activation and proliferation, depending on their stage of maturation. The
      recently classified type III interferon group, interferon-lambda1 (IL-29),
      interferon-lambda2 (IL-28A), and interferon-lambda3 (IL-28B) displays
      immunomodulatory and antiviral activity. In the current study, we describe a way
      to stimulate the DCs maturation. As a result, IFN-lambda1 combined with
      recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and
      recombinant human interleukin-4 (rhIL-4) can induce the DCs maturation and
      promote the costimulatory molecules such as CD80, CD83, CD86 and human leucocyte
      antigen DR (HLA-DR) expression in the immune tolerance and the clearance phases.
      This study demonstrates that the DCs function is remarkably impaired both in the
      immune tolerant phase and the immune clearance phase in adolescents with chronic
      HBV infection compared with healthy youth control. At the same time, this study
      has developed a theoretical basis for the application of IFN-lambda1 breaking
      immune tolerance and improving the body's immune system to clear HBV. 

PMID- 25973064
TI  - Hyperbaric oxygenation promotes neural stem cell proliferation and protects the
      learning and memory ability in neonatal hypoxic-ischemic brain damage.
AB  - The aim of our study was to evaluate whether hyperbaric oxygenation (HBO) was an
      effective therapy for neonatal hypoxic ischemic brain damage (HIBD). Seven-day
      old rat pups were divided into 3 groups: sham, hypoxia-ischemia (HI) control and
      HI-HBO group. HBO was administered for HI rats daily. The pathologic changes in
      brain tissues were observed by hematoxylin-eosin (H-E) staining. The
      immunohistochemical staining was applied to detect the Nestin and 5-bromo-2
      deoxyuridine (BrdU) positive cells in hippocampal dentate gyrus region. The
      learning and memory function of rats was examined by Morris water maze. The HI
      rats showed obvious pathologic changes accompanied by levels decreasing and
      disorder arrangement of pyramidal cells, glial cells proliferation in
      postoperative, and nerve nuclei broken, while pathologic changes of rats in sham
      group was approximate to that in the HI + HBO group that was opposite to the HI
      group. Compared with the sham group, the Nestin and BrdU positive cells in HBO +
      HI group at different time points increased significantly (P < 0.01). Learning
      and memory function of rats in HI group was poor compared with the sham/HI + HBO
      group (P < 0.01), while that in HI + HBO group was approximate to that in sham
      group (P > 0.05). HBO treatment improved the learning and memory ability of the
      HI rats. HBO therapy may be effective for neonatal HIBD treatment. 

PMID- 25973065
TI  - RNAi-mediated silencing of praline-rich gene causes growth reduction in human
      lung cancer cells.
AB  - Lung cancer ranks among one of the most frequent causes of cancer death in the
      world. Here, we investigated PRR11, one novel gene, with no functional
      annotation, was found to be over-expressed in lung cancer patients suggesting its
      potential implication in tumorigenesis. Furthermore, high PRR11 levels predict
      shorter survival of lung cancer patients. In this study, we investigated the
      therapeutic potential of PRR11 in lung cancer using the technique of RNA
      silencing via small interfering RNA (siRNA). Synthetic siRNA duplexes against
      PRR11 were introduced into 3 lung cancer cell lines, which subsequently resulted
      in a significant depletion in PRR11 expression in the cells. We found that the
      targeted depletion of PRR11 caused a dramatic cell cycle arrest followed by
      massive apoptotic cell death, and eventually resulted in a significant decrease
      in growth and viability of all 2 lung cancer cell lines. In summary, our study
      strongly suggests that PRR11 may serve as a potential therapeutic target in human
      lung cancer. 

PMID- 25973066
TI  - Expression and function analysis of indoleamine 2 and 3-dioxygenase in bladder
      urothelial carcinoma.
AB  - Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan
      metabolism inducing immune tolerance of tumors. The purpose of this study is to
      investigate IDO expression and its prognostic significance in bladder urothelial
      carcinoma (BUC). In this study, immunohistochemical staining for IDO expression
      in BUC tissues (n = 84) and normal bladder tissues (n = 22) was performed. The
      mRNA expression levels of IDO in BUC and normal bladder were analyzed by
      quantitative RT-PCR. Survival analysis was performed for the correlation of IDO
      expression and clinicopathological factors with disease-free survival. Positive
      expression of IDO was found in 48 of 84 cases in BUC tissues and was
      significantly correlated with histological classification, histological grade and
      TNM stage. While IDO expression in normal bladder tissues was expressed in only 4
      of 22 (18.2%) cases. Moreover, IDO mRNA levels of BUC were significantly higher
      than that of normal bladder. We also found that IDO, histological grade and TNM
      stage were closely associated with DFS. These results indicated that IDO was
      related to the progression of BUC and might be one of the crucial prognostic
      factors for BUC. 

PMID- 25973067
TI  - Relationship of endothelial area with VEGF-A, COX-2, maspin, c-KIT, and DOG-1
      immunoreactivity in liposarcomas versus non-lipomatous soft tissue tumors.
AB  - Soft tissue tumors are rare tumors that show a heterogeneous structure; thus far,
      their molecular behavior has not been elucidated. The aim of our study was to
      define the relationship between microvessel density (MVD), evaluated with CD31,
      and other immunohistochemical markers, such as vascular endothelial growth factor
      (VEGF), cyclooxygenase-2 (COX-2), CD34, maspin, DOG-1, and c-KIT. Immunostains
      were done in 55 cases consisting of benign and malignant tumors, such as
      liposarcomas, dermatofibrosarcomas, and tumors with histiocytic differentiation.
      Renal tubes were used as external control for VEGF, maspin, and DOG-1. Although
      DOG-1 is considered a specific marker for gastrointestinal tumors (GISTs), its
      positivity, correlated with c-KIT and VEGF immunoexpression, was also shown by
      dermatofibrosarcomas and tumors with histiocytic and lipomatous differentiation,
      suggesting its possible pro-angiogenic role. Maspin expression was observed in
      adipose tissue tumors only. Regarding angiogenesis, 31 of the 55 cases were VEGF
      positive, such positivity being directly correlated with COX-2 and CD34
      positivity as evaluated in the tumor cells and also with MVD. Although no
      significant differences in angiogenic activity were found between benign and
      malignant non-lipomatous tumors, the MVD was directly correlated with the
      histological type/grade of liposarcomas. Based on these aspects, we conclude that
      VEGF/COX-2-induced angiogenesis is specific for non-lipomatous tumors, whereas
      liposarcomas are dependent on the VEGF/maspin angiogenic pathway. The DOG-1/c
      KIT/VEGF target may be used for further personalized therapy of soft tissue
      sarcomas. No data about DOG-1 and maspin positivity in liposarcomas have been
      published to date. 

PMID- 25973068
TI  - Lgr5 is a potential prognostic marker in patients with cervical carcinoma.
AB  - OBJECTIVE: To investigate the Lgr5 (Leucine-rich repeat-containing G protein
      coupled receptor 5) expression in cervical carcinoma and to estimate its clinical
      significance. METHODS: The expression of Lgr5 mRNA was evaluated by Real-time PCR
      in 8 pairs of surgically removed cervical cancer and adjacent normal cervical
      tissues. Lgr5 protein expression was evaluated by immunohistochemistry in 94
      paraffin-embedded cervical carcinoma specimens. The correlation between Lgr5
      expression and clinicopathological features were statistically analyzed. RESULTS:
      Lgr5 expression was significantly higher in cervical cancer tissues compared with
      that in adjacent normal cervix. High Lgr5 expression was positively correlated
      with tumor size (P = 0.025) and parametrial infiltration (P = 0.027). Moreover,
      high levels of Lgr5 was associated with lower overall survival (P = 0.021) and
      recurrent-free survival (P = 0.008), especially in stage II patients (P = 0.035).
      Multivariate analysis showed that the expression of Lgr5 was an independent
      factor of recurrent-free survival for the patients with cervical carcinoma (P =
      0.135). CONCLUSION: Lgr5 may play an important role in the development and
      progression of cervical carcinoma, and may be a potential therapeutic target for
      the treatment of cervical carcinoma.

PMID- 25973069
TI  - Detection of MGMT promoter methylation in glioblastoma using pyrosequencing.
AB  - Recent clinical trials on patients with glioblastoma revealed that O6
      Methylguanine-DNA methyltransferase (MGMT) methylation status significantly
      predicts patient's response to alkylating agents. In this study, we sought to
      develop and validate a quantitative MGMT methylation assay using pyrosequencing
      on glioblastoma. We quantified promoter methylation of MGMT using pyrosequencing
      on paraffin-embedded fine needle aspiration biopsy tissues from 43 glioblastoma.
      Using a 10% cutoff, MGMT methylation was identified in 37% cases of glioblastoma
      and 0% of the non-neoplastic epileptic tissue. Methylation of any individual CpG
      island in MGMT promoter ranged between 33% and 95%, with a mean of 65%. By a
      serial dilution of genomic DNA of a homogenously methylated cancer cell line with
      an unmethylated cell line, the analytical sensitivity is at 5% for pyrosequencing
      to detect MGMT methylation. The minimal amount of genomic DNA required is 100 ng
      (approximately 3,000 cells) in small fine needle biopsy specimens. Compared with
      methylation-specific PCR, pyrosequencing is comparably sensitive, relatively
      specific, and also provides quantitative information for each CpG methylation. 

PMID- 25973070
TI  - Hyperbaric oxygen treatment reduced the lung injury of type II decompression
      sickness.
AB  - OBJECTIVE: To detect the ultrastructural changes in rabbits with type II
      decompression sickness (DCS), and study the therapeutic effects of hyperbaric
      oxygen (HBO). METHODS: Twenty-seven male New Zealand rabbits were randomly
      divided equally into the DCS group, HBO treatment group and control group.
      Experimental models of each group were prepared. Lung apex tissues were harvested
      to prepare paraffin- and EPON812-embedded tissues. RESULTS: In the DCS group,
      macroscopic and histological examination revealed severe and rapid damage to lung
      tissue. Ultrastructural examination revealed exudation of red blood cells in the
      alveolar space. Type I alveolar epithelial cells exhibited retracted cell
      processes and swollen mitochondria, and type II cells showed highly swollen
      mitochondria and decrease in cytoplasmic lamellar bodies. Dilatation and
      congestion of capillary vessels were accompanied by swelling of endothelial cells
      and incomplete basement membrane. In the HBO treatment group, the findings were
      somewhat similar to those in the DCS group, but the extent of damage was lesser.
      Only a small amount of tiny bubbles could be seen in the blood vessels. Type I
      alveolar epithelia cells and endothelial cells of the capillaries illustrated
      slight shortening of cells, swollen cytoplasm and decreased cell processes. Type
      II alveolar epithelial cells showed slight swelling of the mitochondria,
      decreased vacuolar degeneration of lamellar bodies, and increase in the number of
      free ribosomes. CONCLUSIONS: Our microscopic and ultrastructural findings confirm
      that the lung is an important organ affected by DCS. We also confirmed that HBO
      can alleviate DCS-induced pulmonary damage.

PMID- 25973071
TI  - Stomatin-like protein 2 expression is associated with clinical survival in
      patients with cervical cancer.
AB  - AIMS: To investigate the prognostic role of stomatin-like protein 2 (STOML2) in
      cervical cancer. METHODS: The expression of STOML2 in 8 pairs of cervical cancer
      and adjacent normal cervical tissues were detected by Real-time PCR.
      Immunohistochemistry was performed to evaluation of STOML2 expression in 94
      paraffin-embedded cervical cancer samples. The correlation between STOML2
      expression and cervical cancer progression and prognosis was analyzed
      statistically. RESULTS: STOML2 expression was upregulated in cervical cancer
      tissues compared with adjacent normal cervical tissues. Of the 94 cervical cancer
      cases, high STOML2 expression was detected in 54 cases (57.4%). STOML2 expression
      was significantly related to tumor stage (P = 0.013) and tumor size (P = 0.025).
      Moreover, patients with high expression of STOML2 had a significant shorter
      overall survival and recurrent free survival time compared with those with low
      STOML2 expression in cervical cancer (P = 0.001 and P = 0.017, respectively).
      Multivariate analysis revealed that STOML2 was an independent prognostic factor
      (P = 0.022) for the overall survival in cervical cancer. CONCLUSION: Our study
      showed STOML2 was correlated to progression in cervical cancer, and implicated it
      as a potential predictive factor for the prognosis of cervical cancer.

PMID- 25973072
TI  - Expression of focal adhesion kinase in endometrial stromal cells of women with
      endometriosis was adjusted by ovarian steroid hormones.
AB  - The aim of our study is to investigate the effects of ovarian steroid hormones on
      focal adhesion kinase (FAK) expression in ESCs and whether there is alteration in
      women with endometriosis. FAK expression was assessed by western blotting
      analysis. Elevated expression of FAK was seen in the cultured ESCs treated with
      estrogen (P < 0.05). Expression of FAK protein was not changed in ESCs after
      treated by progesterone or treated by estrogen and progesterone. The level of up
      regulation by estrogen in endometriosis is significantly higher than that from
      women without endometriosis (P < 0.05). FAK expression in endometrial stromal
      cells from endometriosis was more sensitive to estrogen, which might contribute
      to the pathogenesis and progress of endometriosis. 

PMID- 25973073
TI  - Activation of autophagy in rats with plateau stress-induced intestinal failure.
AB  - Hypobaric hypoxia may damage the intestinal mucosa, which may induce multiple
      organ dysfunction. However, little work has been done regarding whether high
      altitude hypoxia is associated with failure of the intestinal mucosal barrier.
      The aim of this study was to investigate the change of the autophagy after the
      intestinal failure in rats acutely exposed to plateau stress. Fifty Wistar rats
      were randomly divided into five groups: the plain group, plateau for 6 h, 12 h,
      24 h, and 48 h (n = 10 in each group). The acute exposure to plateau was
      established at a simulated altitude of 4767 meters (m) in a decompression
      chamber. Intestinal injury was verified by light microscopy. The autophagosomes
      in the intestinal epithelial cells were observed by transmission electron
      microscopy (TEM). The protein expression of Beclin1 and LC3B in the intestinal
      epithelial cells were analyzed by immunohistochemistry. Compared with the plain
      group, acute exposure to plateau led to a time-dependent damage of the intestinal
      epithelium. The autophagosome was observed after the intestinal failure following
      acute exposure to high altitude for 6 h. The expression of Beclin1 and LC3B
      protein in the rats exposed to acute plateau for 6 h, 12 h, 24 h and 48 h were
      significantly higher than those in the plain group. The expression of autophagy
      also showed a significant increase in rats with intestinal failure following
      acute exposure to plateau stress. 

PMID- 25973074
TI  - Targeting gallbladder cancer: hyaluronan sensitizes cancer cells to chemo
      therapeutics.
AB  - Gallbladder cancer is the most common biliary tract malignancy and the fifth most
      common gastrointestinal malignancy. Chemo-resistance is the most remarkable
      characteristic of gallbladder cancer. The relatively dense extracellular space in
      tumor is the main barrier to nanotherapeutics' anticancer efficacy. Hyaluronan
      (HA) was shown in our previous study to significantly improve the myxoma virus
      distribution via promoting the MMP-9 production, which degrades collagen IV. We
      demonstrated that HA increased the chemo-sensitivity of gallbladder cancer cells
      both in vitro and in vivo. The in vivo chemo-sensitization effect of HA could
      partially be due to the penetration-promoting effect of HA via degrading collagen
      IV. 

PMID- 25973075
TI  - Crescentic acute glomerulonephritis with isolated C3 deposition: a case report
      and review of literature.
AB  - An eight-year-old girl, presenting with palpebral edema, gross hematuria, and
      foam in urine, was admitted to our hospital. Investigations indicated increased
      serum antistreptolysin O (ASO) and anti-mycoplasma antibody titers. Renal biopsy
      showed crescentic poststreptococcal acute glomerulonephritis (CPAGN) with
      isolated C3 deposition in the glomeruli. Electro-microscope examination showed
      subepithelial deposition of electron dense material. She received the double
      pulse therapies of methylprednisolone and cyclophosphamide as well as the
      treatment of oral prednisolone, angiotensin converting enzyme-II (ACE-II)
      inhibitor, dipyridamole and traditional Chinese medicine. The complete clinical
      remission was achieved after 9 months. No serious adverse effects were observed
      during the follow-up. Our findings indicated that CPAGN with isolated C3
      deposition might have a favorable prognosis after aggressive immunosuppressive
      treatment. However, the influence of isolated C3 deposition on CPAGN prognosis
      remains to be clarified. 

PMID- 25973076
TI  - Time-dependent toxic effects of N-ethyl-N-nitrosourea on the testes of male
      C57BL/6J mice: a histological and ultrastructural study.
AB  - N-ethyl-N-nitrosourea (ENU), a well known alkylating agent, is a powerful mutagen
      in mouse spermatogonia that is frequently used to generate mutant mice for the
      study of gene function. The present study was performed to investigate the toxic
      effects of a suggested ENU treatment protocol (100 mg/kg ENU once a week for
      three consecutive weeks) on the C57BL/6J mouse testis using light and
      transmission electron microscopy, with reference to testis weight and sperm
      count. Time-dependent changes in the weight of the testes, sperm counts and
      testicular morphology were observed, following an injury and recovery pattern;
      the most severe damage was observed in week four after the first injection of
      ENU, and then the testis gradually recovered. By the end of the experiment (week
      12), the testis weights and sperm counts of the ENU-treated mice had restored to
      around 80% of the respective values in the control group. Histopathological
      alterations in the testis were identified by light and electron microscopy, which
      revealed that ENU led to a temporary depletion in the number of spermatogenic
      cells via direct and indirect toxic effects, including apoptosis and growth
      arrest in spermatogonia, Sertoli cell damage and peritubular cell injury. The
      results of this study complement the existing basic information on the toxicity
      of ENU in the testis, and provide scientific information for selecting the
      appropriate mating time for ENU-treated male mice. 

PMID- 25973077
TI  - Hypermethylation of TFPI2 correlates with cervical cancer incidence in the Uygur
      and Han populations of Xinjiang, China.
AB  - Tissue factor pathway inhibitor 2 (TFPI2) is a Kunitz-type serine proteinase
      inhibitor, which plays an important role in the etiology of human malignancies.
      DNA methylation is a common epigenetic modification of the genome that is
      involved in regulating many cellular processes. In addition to human papilloma
      virus (HPV) infection, DNA methylation may play a role in the carcinogenesis of
      cervical cancer. Methylation of 22 CpG sites in the promoter region of the TFPI2
      gene was detected by MassARRAY spectrometry and a gene mass spectrogram was drawn
      using MALDI-TOF MS. HPV16 was detected by PCR. We show that aberrant methylation
      of TFPI2 is present in a higher proportion of invasive cervical carcinoma (ICC)
      clinical samples as compared to normal cervical samples in Uygur and Han. Across
      the four pathologic lesions of the progression of cervical cancer, ICC showed the
      highest level of aberrant methylation, and with a stronger correlation between
      CpG site and lesion grade in Uygur than in Han. Moreover, a difference in TFPI2
      methylation between Uygur patients positive and negative for HPV16 infection was
      observed at CpG_6 (P = 0.028) and CpG_15 (P = 0.007). Altogether, these results
      indicate that DNA methylation of TFPI2 may play an important role in the
      carcinogenesis of cervical cancer and that the differential methylation of TFPI2
      may at least partially explain the disparity in cervical cancer incidence between
      Uygur and Han women. 

PMID- 25973078
TI  - Association between the MARS rs6782181 polymorphism and serum lipid levels.
AB  - Little is known about the association between the muscle Ras (MRAS) gene
      rs6782181 polymorphism and serum lipid levels. The aim of the present study was
      to investigate the association between the MRAS rs6782181 polymorphism and serum
      lipid levels in the Mulao and Han populations. A total of 632 subjects of Han and
      629 unrelated subjects of Mulao nationalities were randomly selected from our
      previous stratified randomized samples. Genotypes of the MARS rs6782181
      polymorphism were determined via polymerase chain reaction and restriction
      fragment length polymorphism. The subjects with GG genotype had higher serum
      total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol
      (LDL-C), and apolipoprotein (Apo) B levels in Han, and higher serum TC and LDL-C
      levels in Mulao than the subjects with AA/AG genotypes (P < 0.05-0.01). Subgroup
      analyses showed that the subjects with GG genotype had higher TC, TG, high
      density lipoprotein cholesterol (HDL-C), LDL-C, ApoAI and ApoB in Han males,
      lower ApoAI and the ratio of ApoAI to ApoB in Han females; and higher LDL-C
      levels in Mulao males but not in Mulao females than the subjects with AG/AA
      genotypes. The association of the MARS rs6782181 polymorphism and serum lipid
      levels is different between the Mulao and Han populations, or between males and
      females in the both ethnic groups. There may be an ethnic- and/or sex-specific
      association between the MRAS rs6782181 polymorphism and serum lipid levels in our
      study populations. 

PMID- 25973079
TI  - Mismatch repair system in endometriotic tissue and eutopic endometrium of
      unaffected women.
AB  - OBJECTIVE: To test the immunohistochemical staining pattern of some mismatch
      repair (MMR) system proteins in endometriotic tissue (ET) and eutopic
      endometrium. METHODS: This was a retrospective study conducted at the Pathology
      and Obstetrics and Gynecology Departments of the Udine University Hospital. We
      analyzed 528 samples obtained from 246 patients affected by endometriosis and 71
      samples from 71 patients with normal endometrium. A tissue microarray model was
      used to analyze the immunohistochemical expression of MMR system proteins.
      RESULTS: Significant loss of MMR proteins was found in the stromal component of
      ETs. We found MSH2 to be expressed at a higher level than any other MMR system
      proteins in eutopic endometrium and ETs, to be significantly correlated to Ki-67
      expression in both stromal and glandular components of ETs, and to be expressed
      at a significantly higher level in ETs than in eutopic endometrium. When
      considering the subgroup of endometriosis with high recurrence rate and glandular
      cytoplasmic staining for aurora A kinase, we found MMR proteins expressed at a
      significantly higher level in these ETs than in other ETs and eutopic endometrium
      of unaffected women. CONCLUSIONS: We found significant loss of MMR proteins
      (known to be associated with microsatellite instability) in the stromal component
      of ETs. The group of ETs with glandular cytoplasmic staining for aurora A kinase
      had higher MMR protein expression, suggesting an increased activity of this
      system. Our result suggests a novel role of increased MSH2 expression in cellular
      proliferation of endometriosis.

PMID- 25973081
TI  - Identification of mannose-binding lectin as a mechanism in progressive
      immunoglobulin A nephropathy.
AB  - Immunoglobulin A nephropathy (IgAN), the pathogenesis of which remained still
      unclear is one of the leading courses of end-stage renal disease in approximately
      50% affected patients. On the basis of several researches, the activation of
      complement mannose-binding lectin (MBL) pathway might be the underlying mechanism
      in disease progress. In order to investigate the relationship between MBL pathway
      and IgAN, we discussed the MBL gene polymorphism as well as its expressed level
      in serum, urine and renal parenchymal, with renal outcome in IgAN patients. The
      significantly down-regulated expression of MBL was discovered, which may serve as
      a potential urinary biomarker in progressive IgAN according to the results of
      difference in gel electrophoresis and matrix-assisted laser desorption/ionization
      time of flight mass spectrometry. The single nucleotide polymorphisms of MBL gene
      in promoter and exon region were found and confirmed relating with the poor
      prognosis of progressive IgAN patients. As a result, the deficient activation of
      MBL pathway caused by the mutation of MBL accompanied with low expressed level of
      MBL in serum might be the potential inspiring regulation in IgAN, and will
      attract a promising insight in remedy of IgAN to inhibit further progress. 

PMID- 25973080
TI  - Nuclear C-MYC expression level is associated with disease progression and
      potentially predictive of two year overall survival in prostate cancer.
AB  - PURPOSE: Upregulation of nuclear C-MYC protein has been reported to be an early
      event in prostate cancer (PCa); however, its clinicopathological and prognostic
      significance remain controversial. We determined the association of nuclear C-MYC
      protein expression with clinicopathological parameters, prognosis, ETS-related
      gene (ERG) expression, and TMPRSS2-ERG status in PCa. METHODS: Nuclear C-MYC and
      ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color
      probe fluorescence in situ hybridization assay were determined in 50 hormone
      naive PCa patients and 31 radical prostatectomy specimens. RESULTS: Nuclear C-MYC
      immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and
      40.0% of cases, respectively. C-MYC immunostaining was significantly associated
      with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P
      < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P =
      0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have
      worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the
      univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI
      0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P
      = 0.040) were significantly associated with 2-year OS. After adjusting for these
      two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049
      0.778; P = 0.020). CONCLUSIONS: Nuclear C-MYC overexpression may be associated
      with disease progression and potentially predictive of 2-year OS in PCa. This is
      the first study to demonstrate an association between nuclear C-MYC
      immunostaining and TMPRSS2-ERG status in PCa.

PMID- 25973082
TI  - Decreased peritherapeutic VEGF expression could be a predictor of responsiveness
      to first-line FOLFIRI plus bevacizumab in mCRC patients.
AB  - OBJECTIVE: Bevacizumab is the only anti-angiogenic agent approved in first-line
      therapy for metastatic colorectal cancer (mCRC). Although chemotherapy plus
      bevacizumab has led to improve outcomes for mCRC patients and is a common choice
      for first-line treatment of mCRC, previous research has established no prominent
      biomarker that can help to select patients who may benefit from bevacizumab in
      order to improve cost-effectiveness and therapeutic outcomes. The aim of this
      study was to compare pre- and post-therapeutic VEGF immunohistochemical (IHC)
      expression in mCRC patients treated with FOLFIRI plus bevacizumab to identify its
      potential role as a predictive biomarker. METHODS: A total of 57 mCRC patients
      who underwent FOLFIRI combined with bevacizumab chemotherapy as a first-line
      neoadjuvant regimen were enrolled and clinical outcome data analyzed. RESULTS:
      Low post-therapeutic VEGF expression (P < 0.001) and decreased peri-therapeutic
      VEGF expression (P < 0.001) were significantly predictive factors of responders.
      Furthermore, the 6-month progression-free survival (PFS) rate in mCRC patients
      with decreased peri-therapeutic VEGF expression was significantly better than the
      rate for those patients with no peri-therapeutic VEGF expression alterations (P =
      0.033). CONCLUSIONS: Decreased peri-therapeutic VEGF expression in mCRC patients
      could probably be used to predict responsiveness to bevacizumab and subsequent
      PFS in clinical practice.

PMID- 25973083
TI  - Association of XRCC3 gene rs861539 polymorphism with gastric cancer risk:
      evidence from a case-control study and a meta-analysis.
AB  - The association between the X-ray repair cross-complementing group 3 (XRCC3) gene
      Thr241Met polymorphism (rs861539) and gastric cancer has been widely evaluated,
      but a definitive answer is so far lacking. We first conducted a case-control
      study to assess this association in a large Han Chinese population, and then
      performed a meta-analysis to further address this issue. Although our case
      control association study and the following meta analysis involving 6,520
      subjects indicated null association of XRCC3 gene rs861539 polymorphism between
      gastric cancer patients and controls under both allelic (odds ratio (OR) = 1.02;
      95% confidence interval (CI): 0.91-1.14; P = 0.739) and dominant (OR = 0.97; 95%
      CI: 0.78-1.21; P = 0.803) models. Stratified analysis by ethnicity demonstrated a
      significant association in Asians. We conclude that the XRCC3 gene rs861539
      polymorphism was associated with the risk for gastric cancer in Asian
      populations. 

PMID- 25973084
TI  - Nuclear maspin expression correlates with the CpG island methylator phenotype and
      tumor aggressiveness in colorectal cancer.
AB  - It has been suggested that nuclear expression of maspin (mammary serine protease
      inhibitor; also known as SERPINB5) in colorectal cancer (CRC) is associated with
      proximal colonic tumor location, mucinous and poorly differentiated histology,
      microsatellite instability-high (MSI-H), and poor prognosis. Based on these
      findings, there may be a potential association between nuclear maspin expression
      and the CpG island methylator phenotype (CIMP) in CRC, but no study has
      elucidated this issue. Here, we evaluated maspin protein expression status by
      immunohistochemistry in 216 MSI-H CRCs. CIMP status was also determined by
      methylation-specific quantitative PCR method (MethyLight) using eight CIMP
      markers (MLH1, NEUROG1, CRABP1, CACNA1G, CDKN2A (p16), IGF2, SOCS1, and RUNX3) in
      216 MSI-H CRCs. Associations between maspin expression status and various
      pathological, molecular, and survival data were statistically analyzed. Among the
      216 MSI-H CRCs, 111 (51%) cases presented nuclear maspin-positive tumors. Nuclear
      maspin-positive MSI-H CRCs were significantly associated with proximal tumor
      location (P = 0.003), tumor budding (P < 0.001), lymphovascular invasion (P =
      0.001), perineural invasion (P = 0.008), absence of peritumoral lymphoid reaction
      (P = 0.045), lymph node metastasis (P = 0.003), distant metastasis (P = 0.005),
      advanced AJCC/UICC stage (stage III/IV) (P = 0.001), and CIMP-high (CIMP-H)
      status (P < 0.001). Patients with nuclear maspin-positive tumors showed worse
      disease-free survival than patients with nuclear maspin-negative tumors (log-rank
      P = 0.025). In conclusion, nuclear maspin expression is molecularly associated
      with CIMP-H rather than MSI-H, and clinicopathologically correlates with tumor
      aggressiveness in CRC. 

PMID- 25973085
TI  - CD147 and MMP-9 expressions in type II/III adenocarcinoma of esophagogastric
      junction and their clinicopathological significances.
AB  - OBJECTIVES: To investigate CD147 and matrix metalloproteinase-9 (MMP-9)
      expressions in type II/III adenocarcinoma of esophagogastric junction (AEG), and
      their clinicopathological significances. METHODS: Seventy-four patients
      clinically and pathologically diagnosed with type II/III AEG were analyzed, each
      undergoing radical total gastrectomy and Roux-en-Y esophagojejunostomy. The
      avidin streptavidin-perosidase immunohistochemistry technique was used to detect
      CD147 and MMP-9 in type II/III AEGs and 20 para-tumor controls, and their
      correlations with clinicopathological data and their reciprocal relationship were
      then analyzed. Kaplan-Meier survival analysis was conducted to reveal their
      prognostic significances. SPSS 20.0 was used for data analysis. A difference was
      statistically significant with P < 0.05, and very significant with P < 0.01.
      RESULTS: In type II/III AEG CD147 and MMP-9 were mainly expressed on cellular
      membrane of in tumor cell cytoplasm. MMP-9 expression was significantly stronger
      at tumor-stroma junction and front edge of invasion. Their positive rates were
      significantly higher in malignant tissues than para-tumor tissues (P < 0.01 for
      both). There existed a significant positive correlation between both expressions
      (P < 0.05). They were significantly more highly expressed in cancers with
      lymphatic metastasis (P < 0.01 for both), at TNM III/IV stages (P < 0.01 for
      both), and with poor differentiation grade (P < 0.05 for both). Higher CD147 and
      MMP-9 expression rates were correlated with inferior postsurgical survivals (P <
      0.05 for both). CONCLUSIONS: CD147 and MMP-9 could be novel biomarkers for type
      II/III AEG, and potentially predict tumor progression and prognosis. They are
      worth further investigation.

PMID- 25973086
TI  - High expression of Sirt7 served as a predictor of adverse outcome in breast
      cancer.
AB  - OBJECTIVE: Sirt7, as one of the seven Sirtuin family members, which plays
      distinct roles in cancer progression, is bringing emerging attention due to its
      oncogenic characteristic. The expression of Sirt7 in breast cancer remained
      unclear, and the aim of this study was to elucidate its role in breast cancer.
      METHODS: A total of 188 cases included in this study were immunohistochemically
      evaluated for Sirt7, and western blot assay was used to assess its expression in
      breast cell lines as well as 36 breast cancer tissues and 36 paired non-cancerous
      tissues. RESULTS: Upregulation of Sirt7 was found in breast cancer cell lines and
      breast cancer tissues (P < 0.001) by western blot analysis. Sirt7 was highly
      expressed in breast cancer tissue samples (67.8%) compared to adjacent normal
      breast tissues (31.8%) by immunohistochemical assay. It was also observed that
      the high expression level of Sirt7 was significantly correlated with high
      histological grade (P = 0.039) and negatively related to overall survival (P =
      0.006). Sirt7 proved to be an independent prognostic factor (P = 0.007) in breast
      cancer. CONCLUSIONS: Sirt7 expression was implicated with high histological grade
      and independently predicted poor clinical outcome in patients with breast cancer,
      suggesting that Sirt7 might play a role in the malignant progression of breast
      cancer.

PMID- 25973088
TI  - Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor
      growth and metastasis in bladder cancer.
AB  - INTRODUCTION: long non-coding RNAs (lncRNAs) are emerging as new regulators in
      the cancer paradigm, the involvement of lncRNAs in urothelial carcinoma of the
      bladder (UCB) is just beginning to be studied. In this study, we focused on
      lncRNA SPRY4-IT1 and investigated its expression pattern, clinical significance,
      and biological function in UCB. METHODS: SPRY4-IT1 expression in UCB tissues was
      examined by quantitative Real-time PCR (qRT-PCR) and its correlation with
      clinicopathological features and patient prognosis was later analyzed. Moreover,
      in vitro assays were performed to explore its role in bladder cancer progression.
      RESULTS: SPRY4-IT1 expression was elevated in UCB tissues, and SPRY4-IT1 levels
      were highly positively correlated with histological grade, tumor stage, and lymph
      node metastasis and reduced overall survival. A multivariate analysis showed that
      SPRY4-IT1 expression is an independent prognostic factor of overall survival in
      patients with UCB. Additionally, the results of in vitro assays showed that the
      suppression of SPRY4-IT1 expression in bladder cancer cells significantly inhibit
      cell proliferation, migration, and invasion. CONCLUSIONS: Our data suggested that
      lncRNA SPRY4-IT1 is a novel molecule involved in bladder cancer progression,
      which provide a potential prognostic biomarker and therapeutic target.

PMID- 25973087
TI  - Expression of heat-shock protein gp96 in gallbladder cancer and its prognostic
      clinical significance.
AB  - PURPOSE: To detect the expression and prognostic clinical significance of heat
      shock protein gp96 (HSP gp96) in gallbladder cancer. METHODS:
      Immunohistochemistry was used to detect and compare the rate of HSP gp96
      expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67
      of chronic cholecystitis. The association of clinicopathological factors and
      patients' survival were calculated by univariate and multivariate (Cox
      proportional hazard regression method) analysis. RESULTS: The expression positive
      rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in
      gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The
      positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher
      than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01).
      Multivariate and Cox regression analysis showed that positive of HSP gp96 (P =
      0.026) expression was an independent poor prognostic predictor in gallbladder
      cancer. CONCLUSIONS: HSP gp96-positive expression is closely correlated with poor
      survival in gallbladder cancer.

PMID- 25973089
TI  - Significance of liver biopsy for the evaluation of methotrexate-induced liver
      damage in patients with rheumatoid arthritis.
AB  - It is well recognized that long-term administration of methotrexate (MTX) in
      patients with rheumatoid arthritis (RA) can induce liver fibrosis via a
      steatohepatitis-like inflammatory process. Several non-invasive tests have been
      investigated as alternatives to liver biopsy, which is, however, still recognized
      as a final diagnostic modality to detect the MTX-induced liver damage. To clarify
      whether there is a significant discrepancy between clinical estimations and
      pathologic findings of this hepatic condition, we performed a following
      comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced
      liver damage were reviewed. The severity of hepatic damage estimated clinically
      was compared with histopathologic findings. Consequently, the liver biopsies
      showed the relatively earlier stages of and milder degrees of hepatic damages
      than the clinical estimations. The histopathologic findings were more reliable
      and useful than any other clinical examinations, to plan and modify the treatment
      strategies, especially in cases of liver damages with multiple etiologies besides
      MTX. These findings suggest that liver biopsy is an unavoidable examination to
      assess precisely MTX-induced liver damage. Non-invasive tests may be useful to
      monitor the hepatic condition of RA patients receiving MTX but do not constitute
      an acceptable alternative to liver biopsy. 

PMID- 25973090
TI  - Down-regulation of microRNA-124 is correlated with tumor metastasis and poor
      prognosis in patients with lung cancer.
AB  - INTRODUCTION: MicroRNA-124 (miR-124) has been proven dysregulated in several
      human malignancies and correlated with tumor progression. However, its expression
      and clinical significance in non-small cell lung cancer (NSCLC) is still unclear.
      Thus, the aim of this study was to investigate the clinical significance of miR
      124 expression in NSCLC. METHODS: Expression levels of miR-124 in 92 pairs of
      NSCLC and adjacent non-tumor tissues were detected by quantitative real-time PCR
      (qRT-PCR). In order to determine its prognostic value, overall survival (OS) and
      disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and
      multivariate analysis was performed using the Cox proportional hazard analysis.
      RESULTS: miR-124 expression level was significantly lower in NSCLC tissues
      compared with adjacent non-tumor tissues (P < 0.05). The 5-year OS of low miR-124
      expression group was significantly shorter than that of high miR-124 expression
      group (P < 0.05). Moreover, the 5-year DFS of low miR-124 expression group was
      also significantly shorter than that of high miR-124 expression group (P < 0.05).
      In a multivariate Cox model, we found that miR-124 expression was an independent
      prognostic factor for both 5-year OS and 5-year DFS in NSCLC (P < 0.05).
      CONCLUSIONS: Our results offer the convincing evidence that miR-124 may play key
      roles in the progression of lung cancer and that the down-regulated expression of
      miR-124 may be independently associated with shorter OS and DFS of patients,
      suggesting that miR-124 might be a potential marker for further risk
      stratification in the treatment of lung cancer.

PMID- 25973091
TI  - Galectin-1 reduction and changes in T regulatory cells may play crucial roles in
      patients with unexplained recurrent spontaneous abortion.
AB  - To investigate the changes of Galectin-1 and T-lymphocyte phenotypes in
      unexplained recurrent spontaneous abortion (URSA). Totally 60 participants were
      recruited and divided into 3 groups in average: pregnant patients with URSA (URSA
      group), normal early pregnant women with induced abortion (IA group) and normal
      non-pregnant women (control group). After the tissue and blood sample were
      collected, Galectin-1 was measured using enzyme-linked immunosorbent assay. Then
      the proportion of T regulatory cells was determined by flow cytometry. The
      expression levels of Galectin-1 in IA group and URSA group was significantly
      higher than that in the control group (24.30 +/- 3.06 and 6.23 +/- 2.41 vs. 1.30
      +/- 0.66, P < 0.05). Besides, the expression level of Galectin-1 in URSA group
      was lower than that in IA group (P < 0.05). The percentage of
      CD4(+)CD25(+)Foxp3(+) Tregs was lower in URSA group than IA group (0.77 +/- 0.31
      vs. 1.00 +/- 0.35, P < 0.05) and the ratio of CD4(+)CD25(+)Foxp3(+)/CD4(+) in
      URSA group was also obviously lower than that in IA and control group (P < 0.05).
      Galectin-1 and CD4(+)CD25(+)Foxp3(+) may play essential roles in maintaining a
      normal pregnancy and their reduction may involve in the pathogenesis of URSA. 

PMID- 25973092
TI  - Roles of claudin-5 and von Willebrand factor in patients with rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affects
      approximately 1% of the world's population. The pathogenesis of RA is not
      understood fully. It is assumed that endothelial function is associated with the
      proinflammatory state of RA. Endothelial dysfunction/activation reflects the
      increased level of von Willebrand factor (vWF) and a shift toward prothrombotic
      activity of the endothelium. The present study was performed to investigate the
      possible relationships between vWF and claudin-5 and the level of disease
      activity in patients with RA. The study population was divided into four groups
      according to the disease activity score in 28 joints (DAS28): remission group
      (RG), 18 patients (DAS28 < 2.6); low disease activity group (LDAG), 23 patients
      (DAS28 > 2.6-3.2); moderate disease activity (MDAG), 23 patients (DAS28 > 3.2
      5.1); high disease activity group (HDAG), 14 patients (DAS28 > 5.1); and control
      group (CG), 10 healthy subjects. Claudin-5 and vWF assessment were derived from
      serum samples gathered from the patients known to have RF and anti-CCP titers in
      the normal ranges. A high positive association of claudin-5 and vWF with the MDAG
      was observed (P < 0.001). The results of our study indicated that the
      relationship between vWF and claudin-5, which are indicators of endothelial cell
      dysfunction and tight junction activity, may be a predictor of disease activity.
      Further studies are required to investigate these pathways to shed light on the
      roles of claudin-5 and vWF in the progression of inflammation and other vascular
      conditions. 

PMID- 25973093
TI  - Increased MT2-MMP expression in gastric cancer patients is associated with poor
      prognosis.
AB  - Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that
      contribute to tumorigenesis and metastasis due to their ability to degrade the
      extracellular matrix (ECM) and basement membrane. In despite of many reports in
      other solid tumors, the role of membrane type-2 MMP (MT2-MMP) in gastric cancer
      (GC) remains to be elucidated. The aim of this study was to investigate MT2-MMP
      expression in human GC tissue microarray (TMA) samples using immunohistochemistry
      (IHC). We found that MT2-MMP expression in tumor tissues was significantly higher
      compared to peritumoral tissues (P < 0.01). However, there were no statistically
      significant differences between MT2-MMP expression and clinicopathological
      parameters. In addition, univariate and multivariate Cox regression analysis
      showed GC patients with high MT2-MMP expression have poor overall survival (OS)
      compared to patients with low MT2-MMP expression (P = 0.013, P = 0.040,
      respectively). In conclusion, MT2-MMP is involved in GC invasion and metastasis
      and may serve as an independent prognostic factor for GC patients. 

PMID- 25973094
TI  - Association of CD14 and TLR4 with LPS-stimulated human normal skin fibroblasts in
      immunophenotype changes and secretion of TGF-beta1 and IFN-gamma.
AB  - OBJECTIVES: We attempted to explore the association of CD14 and TLR4 with LPS
      stimulated human normal skin fibroblasts in immunophenotype changes and secretion
      of TGF-beta1 and IFN-gamma, and to expand the current knowledge of the mechanisms
      that underlie LPS-induced scar formation. METHODS: We randomized the human normal
      skin fibroblasts cultured in vitro into four groups. The expression profile of
      immune phenotypes was determined by immunohistochemical staining. Ultrastructure
      of cells was observed by use of transmission electron microscopy. Secretion
      status of TGF-beta1 and IFN-gamma was inspected using ELISA assay. RESULTS:
      Compared with group A, the expressions of alpha-SMA and alpha1 (I) procollagen in
      groups B, C, D were lower, and it in group D were the lowest in all groups. The
      cells in group A were diversification under the electron microscope, and the
      ratio of the nuclear to plasma of the fibroblasts was large, with unregular
      nuclear membrane, more Golgi apparatus, rough endoplasmic reticulum, and
      microfilament and canaliculus appeared. The ultrastructure of the fibroblasts in
      group B, C, D was spindle and the nuclear was large, with regular nuclear
      membrane, more Golgi apparatus, rough endoplasmic reticulum. ELISA assay
      indicated that the secretion of TGF-beta1 markedly lowered in groups B, C, D in
      comparison to group A, with the most marked decline observed in group D.
      Interestingly, we found significantly increased IFN-gamma secretion in groups B,
      C, D (P < 0.05), with the latter group showing the most notable increase (P <
      0.01). CONCLUSION: These data suggest that both combined and isolated use of CD14
      and TLR4 significantly reduce alpha-SMA expression levels, the number of alpha1
      (I) pro-collagen positive cells, and TGF-beta secretion, while substantially
      increased IFN-gamma secretion. The reduction and increase are especially notable
      when pretreating with CD14 and TLR4 combined. Here we thus draw a conclusion that
      both CD14 and TLR4 are associated with the immunophenotype changes and secretion
      of TGF-beta1 and IFN-gamma in LPS-stimulated human normal skin fibroblasts.

PMID- 25973095
TI  - Melanocortinergic circuits from medial vestibular nuclei to the kidney defined by
      transneuronal transport of pseudorabies virus.
AB  - This study was designed to assess whether MC4R signaling existed in vestibular
      nuclei modulated the activity of kidney by a virally mediated transsynaptic
      tracing study. Pseudorabies virus (PRV)-614 was injected into the kidney in adult
      male MC4R-green fluorescent protein (GFP) transgenic mice (n = 5). After a
      survival time of 5 days, the mice were assigned to humanely sacrifice, and the
      brainstem were removed and sectioned, and processed for PRV-614 visualization.
      The neurochemical phenotype of MC4R-GFP-positive neurons was identified using
      fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons
      were detected in medial vestibular nuclei. Our findings support the hypothesis
      that there exist melanocortinergic circuits from medial vestibular nuclei to the
      kidney. 

PMID- 25973096
TI  - Comparison of the neuroprotective effects and recovery profiles of isoflurane,
      sevoflurane and desflurane as neurosurgical pre-conditioning on
      ischemia/reperfusion cerebral injury.
AB  - BACKGROUND: There are a few reports regarding the comparison of these anesthetic
      agents, but previous studies mainly focus on the veterinary anesthesiology. Less
      attention has been focused comparing the effectiveness of these inhalational
      anesthetic agents in neurosurgery. This lack of interest is regretful
      particularly considering the fact that anesthetics during neurosurgery are an
      issue of extreme sensitivity and subtlety, where the cerebral oxygenation process
      plays a significant role in the neuroprotective mechanisms. OBJECTIVE: The
      purpose of this retrospective study is to contribute to the existing knowledge of
      the comparative studies of the volatile anesthetic agents such as isoflurane,
      sevoflurane and desflurane by evaluating the maintenance and emergence
      characteristics after volatile anesthetics-induced preconditioning with
      isoflurane, sevoflurane or desflurane for inpatient ischemia/reperfusion cerebral
      injury during cerebral or neural surgeries. METHODS: The aim was to investigate
      their neuroprotective mechanisms and effects by analyzing and comparing the
      superiority of each agent in a Chinese patient population, in terms of faster
      emergence, and early and intermediate recovery. The intraoperative haemodynamic
      profiles and postoperative adverse effects of these three agents were also
      systematically analyzed. RESULTS: We found that sevoflurane, when compared with
      isoflurane and desflurane, provided anesthesia with similar hemodynamic stability
      but allowed for a smoother, more rapid emergence and better quality of induction
      and recovery to surgical patients under clinical conditions, particularly to
      those who were experiencing substantial cerebral vasodilation. CONCLUSION:
      Sevoflurane offers several advantages, including a relative lack of airway
      irritation, a more rapid onset and recovery, and greater hemodynamic stability
      than other potent inhaled agents. These properties would appear to afford
      sevoflurane significant clinical potential.

PMID- 25973097
TI  - Correlation between calcification and bone sialoprotein and osteopontin in
      papillary thyroid carcinoma.
AB  - The correlation between calcification and papillary thyroid carcinoma has
      received increasing attention. We investigated the ability of bone sialoprotein
      (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid
      carcinoma (PTC), and explored the correlation between BSP and OPN protein levels
      and calcification in PTC. Archival PTC specimens from patients with PTC with
      calcification and lateral cervical lymph node metastasis (LNM) were included in
      this retrospective immunohistochemical study. The protein levels of BSP and OPN
      were analysed immunohistochemically using routinely prepared tissue sections. PTC
      specimens from 66 patients with PTC were reviewed retrospectively (25 patients
      with histological calcification seen in paraffin sections, 41 patients without
      calcification; 35 patients with lateral cervical LNM, 31 patients without LNM).
      The percentage of samples that had cells that demonstrated positive protein
      staining differed significantly between PTC specimens, benign thyroid nodules,
      and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%,
      respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a
      significant difference in the immunohistochemical score (IHS) for BSP and OPN
      protein staining between PTC specimens with and without calcification (P < 0.05).
      The level of BSP protein staining was found to be significantly correlated with
      the level of OPN protein staining in PTC specimens. We conclude that the strong
      correlation between BSP and OPN and PTC suggests a role for BSP and OPN in
      calcification and tumor progression of PTC. BSP and OPN might be useful tumour
      markers for the diagnosis of PTC with limited value, because both of them had low
      specificity. 

PMID- 25973098
TI  - Polymorphisms in the DUSP10 gene are associated with sex-specific colorectal
      cancer risk in a Han population.
AB  - AIMS AND BACKGROUND: Colorectal cancer (CRC) is common, especially in developed
      countries. CRC is a multifactorial disease influenced by both environmental and
      genetic factors. In this study, we investigated the role of genetic polymorphisms
      in the dual specificity protein phosphatase 10 (DUSP10) gene especially in sex
      specific. METHODS: We selected nine DUSP10 tag single nucleotide polymorphisms
      (tSNPs) previously reported to be associated with colorectal cancer risk of in a
      case-control study from Xi'an city of China. RESULTS: In females, three SNPs were
      associated with decreased CRC risk: rs11118838, rs12724393, and rs908858.
      However, in males, only one SNP, rs908858, was associated with decreased CRC
      risk. Using a log-additive model, the rs11118838 "C" allele and the rs12724393
      "G" allele were associated with decreased CRC risk in females, while the rs908858
      "G" allele was associated with decreased CRC risk in both females and males. In
      addition, haplotype analysis also found "CG" and "CCT" were associated with the
      decreased CRC risk in females. CONCLUSIONS: Our findings suggest that DUSP10
      polymorphisms influence the risk of developing CRC in Han Chinese and emphasize
      that sex should be considered in the design and analysis of health studies and
      biomedical research.

PMID- 25973099
TI  - Candidate pathways and genes for nasopharyngeal carcinoma based on bioinformatics
      study.
AB  - PURPOSE: To reveal the potential microRNAs (miRNAs), genes, pathways and
      regulatory network involved in the process of nasopharyngeal carcinoma (NPC) by
      using the method of bioinformatics. METHODS: Gene expression profiles GSE12452
      (31 NPC and 10 normal samples) and GSE53819 (18 NPC and 18 normal samples), as
      well as miRNA expression profiles GSE32960 (312 NPC and 18 normal samples) and
      GSE36682 (62 NPC and 6 normal samples) were obtained from Gene Expression Omnibus
      database. The differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) between
      NPC and normal samples were identified by using t-test based on MATLAB software
      (FDR < 0.01), followed by pathway enrichment analysis based on DAVID software (P
      value < 0.1). Then, DEmiRNA-DEG regulatory network was constructed. RESULTS: A
      total of 1254 DEGs and 107 DEmiRNAs were identified, respectively. Then, 16
      pathways (including cell cycle) and 32 pathways (including pathways in cancer)
      were enriched by DEGs and target genes of DEmiRNAs, respectively. Furthermore,
      DEmiRNA-DEG regulatory network was constructed, containing 12 DEmiRNAs (including
      has-miR-615-3P) and 180 DEGs (including MCM4 and CCNE2). CONCLUSION: has-miR-615
      3p might take part in the pathogenetic process of NPC through regulating MCM4
      which is enriched in cell cycle. The DEmiRNAs identified in the present study
      might serve as new biomarkers for NPC.

PMID- 25973100
TI  - STAT3 and STAT5b polymorphism contributes to breast cancer risk and clinical
      outcomes.
AB  - We conducted a case-control study in a Chinese population, and investigated the
      role of STAT3 rs4796793 and STAT5b rs6503691 polymorphisms in the risk and
      clinical outcome of breast cancer. STAT5b rs6503691 polymorphisms and STAT3
      rs4796793 polymorphisms were genotyped by TaqMan SNP Genotyping Assays on the ABI
      7500 fast real-time PCR platform. Unconditional logistic regression analyses
      showed that subjects carrying the GG genotype of STAT3 rs4796793 had a
      significantly increased risk of breast cancer, with an adjusted OR (95% CI) of
      0.35 (0.12-0.95). In the Cox proportional hazards model, we observed that
      individuals carrying CG+GG genotype of STAT3 rs4796793 was associated with
      reduced risk of death from breast cancer when compared with CC genotype (HR =
      0.43, 95% CI = 0.20-0.93). Our study found that STAT3 rs4796793 polymorphism
      plays an important role in influence the development and overall survival of
      breast cancer patients. 

PMID- 25973101
TI  - MC4R expression in pedunculopontine nucleus involved in the modulation of
      midbrain dopamine system.
AB  - BACKGROUND AND OBJECTIVE: Separate studies have implicated the pedunculopontine
      tegmental nucleus (PPTg) in processing aversive stimuli to dopamine systems, and
      melanocortin-4 receptor (MC4R) are broadly expressed by the neurons in the PPTg,
      but the exact neurosubstrate underlying the regulation of dopamine systems by the
      central melanocortin pathway is poorly understood. METHODS: In this study, the
      PPTg of 6 adult mice expressing green fluorescent protein (GFP) under the control
      of the MC4R promoter was detected by fluorescence immunohistochemistry. RESULTS:
      A large number of GFP-positive neurons in the dissipated parts of PPTg (dpPPTg)
      were found, and approximately 50% of MC4R-GFP- positive neurons in the dpPPTg
      coexpressed tyrosine hydroxylase, a marker of dopamine neurons, indicating that
      they were dopaminergic. CONCLUSIONS: Our findings support the hypothesis that
      MC4R signaling in the dpPPTg may involve in the modulation of midbrain dopamine
      systems.

PMID- 25973102
TI  - Single nucleotide polymorphisms of ERbeta and coronary atherosclerotic disease in
      Chinese Han women.
AB  - BACKGROUND: Growing evidence has shown that with the increase of age, the
      incidence of coronary atherosclerotic disease (CAD) in women increases to equal
      that of men. Several studies on the single nucleotide polymorphisms [SNPs] seem
      to provide evidence in support of the protective role estrogen receptor beta
      (ERbeta) has in reducing the risk of CAD. OBJECTIVE: To determine the association
      of ERbeta SNPs rs1256049 RsaI 1082 A > G and rs4986938 AluI 1730 G > A with
      coronary atherosclerotic disease in Chinese Han women. METHODS: We designed a
      nested case-control research, in which 120 case women and 30 control women were
      selected from the Forensic Medicine Department of Tongji Medical College, HUST.
      We isolated DNA from their lung paraffin blocks, and then screened for these two
      SNPs for each DNA sample. Post-statistical analysis of their genotypes and
      haplotypes was used to figure out the targeted association. RESULTS: We found no
      significant difference between the genotypes or haplotypes of the two SNPs and
      the risk of CAD. However, the rs4986938 heterozygote AG variant was correlated
      with a significantly lower risk for CAD than did homozygote GG variant in the
      group of less than 40 years old. Haplotype AA of the two SNPs was correlated with
      a higher risk for CAD in the same group. CONCLUSION: The rs4986938 AluI 1730 G >
      A seems to be quite involved in the genetic basis of the disease and needs more
      attention in future studies. Meanwhile, this very association made between CAD
      and the mentioned SNP seems to be affected quite a bit by age.

PMID- 25973103
TI  - Mean platelet volume in patients with biliary and non-biliary acute pancreatitis.
AB  - INTRODUCTION: Acute pancreatitis (AP) is a systemic inflammatory disease. We
      aimed to detect whether there was a change of mean platelet volume (MPV) level on
      onset and remission patients with biliary and non-biliary acute pancreatitis.
      MATERIALS AND METHODS: In our emergency service patients diagnosed with biliary
      and nonbiliary AP were analyzed retrospectively. Laboratory results measured in
      onset and remission were recorded and compared. RESULTS: Total number of patients
      enrolled in our study was 331 (177 female). 194 cases were classified as biliary
      and 137 were as non-biliary AP. Average age and numbers of female patients of
      biliary cases were higher than that of nonbiliary cases. Initial MPV values were
      lower than remission values in all patients with AP. In biliary group initial MPV
      was 8.42 +/- 1.04 and remission value was 8.71 +/- 1.12. In nonbiliary group
      initial MPV was 8.07 +/- 1.02 and remission value was 8.4 +/- 1.06. In both
      groups on onset had lower mean MPV levels than those in remission (P = 0.0001
      both of them). CONCLUSIONS: MPV values were higher than initial values in
      remission period in patients both of groups. MPV was lower in non-biliary AP
      group than biliary AP group that can be an indicator of early-onset infection.

PMID- 25973105
TI  - Significance of plasma hepatocyte growth factor in diagnosis of benign and
      malignant solitary pulmonary nodules.
AB  - PURPOSE: We aimed to figure out the difference of serum hepatocyte growth factor
      (S-HGF) level between benign and malignant solitary pulmonary nodules (SPNs)
      patients. METHODS: The study comprised 42 serum samples from SPNs patients and 10
      serum samples of healthy donors. The HGF level was measured by the commercially
      enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: By statistical analysis,
      the S-HGF levels of the malignant SPNs patients were significantly higher than
      that of control group (P < 0.05). Moreover, the levels of S-HGF in malignant
      group were also significantly higher than that in benign group (P < 0.05), while
      there was no significant difference between the benign and control group (P >
      0.05). The levels of S-HGF were also shown no statistically significant
      difference (P > 0.05) in different pathologic types of lung cancer patients. In
      addition, the incidence of malignant SPNs increased when the S-HGF level >= 250
      pg/ml. CONCLUSION: The detection of S-HGF level may be a new detection method
      used for the rapid diagnosis of benign and malignant SPNs.

PMID- 25973104
TI  - Association of LIG4 and XRCC4 gene polymorphisms with the risk of human glioma in
      a Chinese population.
AB  - We conducted a case-control study to assess the LIG4 and XRCC4 genes
      polymorphisms and development of glioma. A case-control study including 162
      glioma cases and 324 controls was conducted in a Chinese population. Genotypes of
      rs10131 and rs1805388 in LIG4 and rs2075685 and rs1805377 in XRCC4 were conducted
      by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)
      assay. Conditional logistic regression analysis showed that subjects carrying AA
      genotype of LIG4 rs10131 was associated with increased risk of glioma when
      compared with GG genotype, and the OR (95% CI) was 3.26 (1.50-7.23). We found
      that GA+AA of LIG4 rs10131 was associated with increased risk of glioma in those
      without family history of cancer, and the OR (95% CI) was 1.78 (1.12-2.83).
      However, no association was found between variants of LIG4 rs1805388, XRCC4
      rs2075685 and XRCC4 rs1805377 and development of glioma. In conclusion, our
      results suggest that LIG4 rs10131 polymorphism in the DNA repair pathways plays
      an important role in the risk of glioma in a Chinese population. 

PMID- 25973106
TI  - Chondrosarcoma of the larynx: report of two cases and review of the literature.
AB  - Primary chondroid tumors of the larynx represent less than 1% of all laryngeal
      tumors. Most of them are chondromas and they often involve to the cricoid
      cartilage. They are characterized by a low tendency to metastatic diffusion (low
      grade). The treatment of choice is surgery, which may be endoscopic or "open
      partial surgery", if extension of the cancer is limited. Prognosis is generally
      good. In this report, two cases of low grade chondrosarcoma of the larynx are
      presented, one was treated surgically with cricoidectomy and partial
      laryngectomy, and another was treated surgically with hemicricoidectomy.
      Laryngoscopy reveals tumefaction of the larynx, covered by intact mucosa.
      Computerized tomography imaging with contrast and magnetic resonance imaging
      defines not only coarse calcifications, pathognomonic of chondromatous
      neoformations but also the relationship of the neoformation with the surrounding
      tissues. Treatment is essentially surgical, given the importance of preserving
      the larynx to patients' quality of life, the only risk is recurrence, which is
      treated by a second surgery. 

PMID- 25973107
TI  - CT-guided needle biopsy in the diagnosis of lung adenocarcinoma accompanied by
      extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a rare
      combination.
AB  - We represent a rare case of lung adenocarcinoma accompanied by extranodal
      marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The patient
      was a 66-year-old male presented with 1 month history of recurrent cough and
      hemoptysis. Chest CT showed solitary ground-glass opacity (GGO) in the upper lobe
      of the right lung and mediastinal lymph node enlargement in station 3p. A CT
      guided transthoracic needle biopsy was performed. Tissue specimens of the GGO
      revealed a typical adenocarcinoma. Histopathologic diagnosis of mediastinal lymph
      node was extranodal marginal zone lymphoma of MALT. Because of its rarity,
      extranodal marginal zone lymphoma of MALT should be considered in the
      differential diagnosis when we encounter mediastinal lymphadenopathy in patients
      with lung adenocarcinoma. 

PMID- 25973108
TI  - Gliosarcoma with primitive neuroectodermal, osseous, cartilage and adipocyte
      differentiation: a case report.
AB  - We describe a rare case of gliosarcoma with primitive neuroectodermal, osseous,
      cartilage and adipocyte differentiation. A 57-year-old man experienced a month
      history of headache, nausea and vomiting. Worse yet, the headache has become more
      severe for the past 6 days. Magnetic resonance (MR) images disclosed a lesion
      with operative indications located in the right frontal lobe. Then the tumor was
      macroscopically totally removed. Histologically, the tumor showed two kinds of
      components. One kind of the tumor cells appeared typical astrocytic tumor cells
      with anaplastic appearance. The other kind of the tumor cells appeared sheets of
      small round hyperchromatic cells, which presented a kind of pancreatic
      neuroendocrine tumor (PNET)-like structure. These sheets of small round cells
      were surrounded by a large number of relative-sparse-spindle cells. Multiple
      separate distinct areas of adipose tissue, osteoid matrix laid down and cartilage
      tissue were also identified. Immunohistochemically, a portion of typical
      astrocytic tumor cells and some small round hyperchromatic cells showed GFAP
      positivity. Small round hyperchromatic cells were positive for S-100, Fli-1,
      Nestin, MAP-2 and Syn. A large amount of relative sparse spindle cells
      (sarcomatous areas) were positive for vimentin. In addition, reticulin staining
      demonstrated expression of reticular fibers in relative-sparse-spindle cells
      areas but not in the astrocytic tumor cells and small round hyperchromatic cells
      areas. Molecular cytogenetic analyses demonstrated PTEN allele loss and no
      evidence of amplification of EGFR in both the astrocytic tumor cells, PNET-like
      structure and sparse spindle cells areas. These data suggest that this tumor was
      a gliosarcoma with primitive neuroectodermal, osseous, cartilage and adipocyte
      differentiation. To our knowledge, this is a rare gliosarcoma , reporting our
      additional new case would add to the better understanding of this tumor. 

PMID- 25973109
TI  - Peripheral ameloblastoma with histologically low-grade malignant features of the
      buccal mucosa: a case report with immunohistochemical study and genetic analysis.
AB  - Peripheral ameloblastoma (PA), a rare and unusual variant of odontogenic tumors,
      comprises about 1% of all ameloblastomas. PA is an exophytic growth localized to
      the soft tissues overlying the tooth-bearing areas of the jaws, and the initial
      diagnosis is often fibrous epulis. PA with histologically low-grade malignant
      features is extremely rare. We report a case of peripheral ameloblastoma with
      histologically low-grade malignant features in a 69-year-old woman that presented
      with a hemorrhage from a tumor on the right buccal mucosa. The tumor was
      surgically removed by blunt dissection, with no evidence of recurrence after two
      years and six months. After the case presentation, microscopic and genetic
      findings are discussed. 

PMID- 25973111
TI  - Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on
      immunohistochemical analyses and literature review.
AB  - Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare
      lesion, with only 21 cases reported in English literature to date. MOM typically
      occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here,
      we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The
      patient did not have complaints; MOM was diagnosed incidentally as 4 flat
      elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in
      maximal diameter, were found in the right torus tubarius. On suspecting melanoma,
      the largest lesion was biopsied. Microscopic examination identified both
      oncocytic metaplasia and melanin pigmentation of the epithelium in the same
      gland. Upon immunohistochemical examination, melanocytes displayed reactivity for
      3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and
      MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the
      nearby surface respiratory epithelium displayed the same pattern of
      immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB
      45 have been previously reported in MOM. Reduction of stimulation of melanocytes
      in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S
      100 protein, in conjunction with more specific marker for melanocytes, Melan-A or
      MITF, could prove the definite presence of melanocytes in this case of MOM. As it
      has been shown by previous reports that MOM pursues a benign course, it will be
      sufficient to follow up the patients regularly for the remaining 3 lesions. 

PMID- 25973110
TI  - Epstein-Barr virus-positive multiple myeloma developing after immunosuppressant
      therapy for rheumatoid arthritis: a case report and review of literature.
AB  - A 61-year-old woman was diagnosed as having rheumatoid arthritis (RA) and began
      treatment with salazosulfapyridine (SASP) and methotrexate (MTX) in 2008; the
      administration of concomitant tacrolimus (TAC) was initiated in 2010. She
      subsequently developed concurrent multiple myeloma (MM), immunoglobulin G (IgG)
      kappa type, in 2012. A portion of the tumor cells tested positive for Epstein
      Barr virus-encoded small RNA (EBER). MTX treatment was discontinued in 2014, and
      the exacerbation of MM ensued. The patient received two cycles of bortezomib plus
      dexamethasone (BD) therapy and attained a complete response (CR). She then
      underwent an autologous peripheral blood stem cell transplantation. The Epstein
      Barr (EB) virus infection arising from the increased RA disease activity and
      immunosuppressant medication might have influenced the development of MM in this
      case. Most reported patients with EB virus-positive plasmacytoma are in a state
      of immunosuppression, and this condition may fall within the category of other
      iatrogenic immunodeficiency-associated lymphoproliferative disorders. No other
      reports of plasmacytoma occurring in a background of RA or after TAC or MTX
      therapy have been made, and the present case is the first such report. 

PMID- 25973112
TI  - Primary myoepithelial carcinoma of the lung: a case report and review of
      literature.
AB  - Primary myoepithelial carcinoma of the lung is a very rare tumor arising from the
      salivary glands of the respiratory epithelium. Since it was first described by
      Higashiyama et al. in 1998, to the best of our knowledge, only eight actual cases
      reported in the English-language literature so far. The diagnosis is based
      entirely on histological and immunohistochemical evaluations. We report a primary
      myoepithelial carcinoma in a smoker 47-year-old Chinese man, who was referred to
      our institution for hemoptysis. Computed tomography revealed a 65 mm * 78 mm
      solid mass in the left lower lobe of lung. The patient underwent the left lower
      lobe resection. The final histopathological diagnosis was primary myoepithelial
      carcinoma of the lung. Given the rare occurrences of this tumor, appropriate
      recommendations for treatment are difficult to formulate. Although classified as
      low-grade tumor, it has a significant rate of distant metastasis. Herein we
      report a case of a primary myoepithelial carcinoma of the lung and present a
      brief review of the literature.

PMID- 25973113
TI  - Dedifferentiation-like progression of breast carcinoma: report of a case showing
      transition from luminal-type carcinoma to triple-negative carcinoma with
      myoepithelial features.
AB  - Certain genetic events that occur at various stages of carcinogenesis can result
      in phenotypic changes. In breast carcinoma, these changes may occur either in
      situ, at the primary invasive site, or at a distant metastatic site. This report
      presents a case of dedifferentiation-like progression of breast carcinoma showing
      transition from luminal-type carcinoma to triple-negative carcinoma (i.e.
      negative for estrogen receptor, progesterone receptor, and HER2) with
      myoepithelial features. An 87-year-old woman was referred to us from another
      hospital for surgery. Preoperative ultrasonography revealed a mass measuring 16 *
      12 * 8 mm. Following partial mastectomy, gross examination revealed a whitish
      tumor on the cut surface measuring 15 * 10 * 8 mm. Histopathological
      investigation revealed a predominant high-grade carcinoma containing some short
      spindle-shaped cells and expressing p63, muscle-specific actin, and alpha smooth
      muscle actin. The tumor also showed decreased expression of pan-cytokeratin and
      increased expression of vimentin on immunohistochemistry. Estrogen receptor was
      not detected by immunostaining. A high Ki-67 labeling index and diffuse nuclear
      accumulation of p53 were observed in the high-grade carcinoma. In the peripheral
      area, low-grade carcinoma with estrogen receptor expression was observed, but
      appeared displaced by the high-grade carcinoma. The high-grade carcinoma
      exhibiting myoepithelial carcinoma-like morphology and molecular phenotype was
      deemed to be carcinoma showing dedifferentiation-like changes arising from the
      peripherally situated pre-existing low-grade carcinoma. Thus, follow-up ought to
      be mandatory, considering the presumably aggressive nature of the predominant
      carcinoma showing dedifferentiation-like changes in this case. 

PMID- 25973114
TI  - Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting in
      nasal cavity: a case report and review of literature.
AB  - Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL)
      is a rare subtype of non-Hodgkin's lymphoma (NHL) with distinct morphologic and
      immunohistochemical features. We reported a 57-year-old female with ALK-positive
      DLBCL in her left nasal cavity. Histologically, the tumor cells were
      characterized by plasmablastic morphology and tested positive for ALK in a
      cytoplasmic granular staining pattern. The neoplastic cells were positive for
      CD38, CD4, MUM1, CD138 and Vimentin. However, they failed to express CD56, CD30,
      as well as mature B cells markers, such as CD79a, CD20 and T cells markers such
      as CD2, CD3, CD5, CD7 and CD8. The patient achieved complete response after four
      cycles of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, and
      etoposide) treatment. Then she received radiotherapy of the originally involved
      area. This case represented a rare ALK-positive DLBCL in the nasal region. 

PMID- 25973116
TI  - Atypical ossifying fibromyxoid tumor unusually located in the mediastinum: report
      of a case showing mosaic loss of INI-1 expression.
AB  - Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue tumor. OFMT mostly
      arises in subcutaneous tissue or skeletal muscle of the extremities and is
      extremely unusual in the mediastinum. OFMT is classified as typical, atypical, or
      malignant as tumor aggressiveness increases. Herein, we presented a case of
      atypical OFMT that developed in the mediastinum of a 43-year-old woman. Because
      of its predominant hypercellular area and some tumor cells with high nuclear
      grade, it was not a typical OFMT. However, it did not have a sufficient number of
      mitotic figures to be classified as malignant. Hence, we classified it as
      atypical OFMT with some apparent characteristic features of OFMT, such as the
      presence of spicules of bone at the periphery of the tumor. Upon
      immunohistochemistry, it was positive for vimentin, S-100 protein, and CD10,
      which was consistent with a diagnosis of OFMT. Particularly noteworthy was the
      mosaic loss of INI-1 expression. Some OFMT and other exceptionally rare tumors
      have been reported to exhibit mosaic INI-1 loss. Inactivation of INI-1 gene and
      deregulation of PHF1 gene are thought to be involved in tumorigenesis of OFMT.
      Therefore, we speculated that the mosaic loss of INI-1 observed in the present
      case might also be related to a kind of abnormality of INI-1 as was reported
      previously. 

PMID- 25973115
TI  - Sporadic renal hemangioblastoma with CA9, PAX2 and PAX8 expression: diagnostic
      pitfall in the differential diagnosis from clear cell renal cell carcinoma.
AB  - To date, 13 cases of sporadic renal hemangioblastoma have been reported. In this
      article, we report such a case that might cause the diagnostic pitfall. A 37-year
      old Japanese was found to have a renal mass by periodic medical check-up. He
      underwent radical nephrectomy. Macroscopically, the tumor was well-defined
      without fibrous capsule and the cut surface of the tumor exhibited light brown to
      gray-tan color without hemorrhage or necrosis. Microscopically, the tumor was
      made up of large polygonal to short spindle cells with eosinophilic cytoplasm
      with occasional vacuolization and abundant arborizing capillary network.
      Immunohistochemically, neoplastic cells showed diffuse positivity for inhibin
      alpha, S-100 protein, vimentin, CA9, PAX2 and PAX8, but negativity for
      cytokeratin CAM5.2, alpha smooth muscle actin, Melanosome, Melan A, TFE3 and
      cathepsin K. In genetic analyses, this tumor showed no changes of VHL gene
      mutation, hypermethylation and loss of heterozygosity of chromosome 3p.
      Additionally, G-band karyotype and array comparative genomic hybridization
      studies showed a normal chromosome. In conclusion, the positivity for CA9, PAX2
      and PAX8 in sporadic renal hemangioblastoma may cause the critical diagnostic
      pitfall in the differential diagnosis from clear cell renal cell carcinoma.
      Pathologists need to pay attention to systemic evaluation including macroscopic,
      microscopic and immunohistochemical findings. In some cases, molecular genetic
      study may be necessary. 

PMID- 25973117
TI  - Pulmonary Langerhans cell histiocytosis with cervical lymph node involvement, and
      coexistence with pulmonary tuberculosis and right pneumothorax: a case report and
      review of literature.
AB  - We report an uncommon 22-year-old male Pulmonary Langerhans Cell Histiocytosis
      (PLCH) case which co-existed with pulmonary tuberculosis (TB). Unlike the common
      PLCH cases, this PLCH case has cervical lymph node involvement and right
      pneumothorax. The diagnosis was established by the imaging of lung and the
      biopsies of the lung and left neck lymph node. Imaging of the chest showed
      characteristic small nodules and thin-walled cysts and right pneumothorax. The
      LCH cells in the lung and left neck lymph node were characterized by large
      convoluted nuclei with cerebriform indentations of the nuclear envelope and
      longitudinal grooves. The nuclei contained small eosinophilic nucleoli and
      moderate amount cytoplasm. Immunohistochemically, the histiocytoid cells were
      positive for Langerin, CD1a and S-100. Acid-fast bacilli were found in sputum and
      lung biopsy tissue. To the best of our knowledge, this is the first case of PLCH
      with cervical lymph node involvement, and coexisted with pulmonary tuberculosis,
      right pneumothorax. A contribution of this case and review three of the five
      cases of PLCH with extrapulmonary involvement to lymph nodes resolved
      spontaneously after smoking cessation constitute a novel addition that it is
      inappropriate to regard pulmonary/nodal LCH as multi-organ or disseminated
      disease, and the treatment methods are the same whether the PLCH patient with
      lymph node involvement or not. 

PMID- 25973118
TI  - Primary epithelioid angiosarcoma of the pleura: a case report and review of
      literature.
AB  - Primary angiosarcoma of the pleura is an extremely rare malignancy. Herein, we
      report the case of an elderly Chinese patient with primary left pleural
      epithelioid angiosarcoma. The 76-year-old man presented with a 4-month history of
      a cough with sputum expectoration and weight loss of 4 kg within one month. A
      chest scan showed a massive oval-shaped mass in the left pleural cavity. We then
      performed a left thoracotomy for tumor resection and surgical exploration.
      Histological examination of the resected specimen showed few viable tumor cells
      with significant atypia; tumor cells had large nuclei and prominent nucleoli and
      were arranged in a crack-like, sheeted pattern. Moreover, there was a significant
      amount of fibrinous exudates, hemorrhage, degeneration, and necrosis. With
      immunohistochemical analysis, tumor cells had strong expression of CD31, CD34,
      FLI-1, vimentin. Morphological and immunohistochemical findings supported the
      diagnosis of epithelioid angiosarcoma. 

PMID- 25973119
TI  - EBV+ diffuse large B-cell lymphoma arising within atrial myxoma in Chinese
      immunocompetent patient.
AB  - The incidence rate of Primary cardiac lymphoma is very low. Primary cardiac
      lymphoma within myxoma is extremely rare disease. So far, these cases have been
      reported only eight in the world, which has not reported in Chinese so far.
      Hence, we reported the unique Chinese case of 52-year-old immunocompetent male
      with primary Epstein-Barr virus positive diffuse large B-cell lymphoma arising
      within atrial myxoma, and had no evidence of systemic lymphoma. The patient
      presented right sided body numbness, arm weakness no incentive and mouth twitch.
      A transthoracic echocardiogram revealed a large intraatrial mass, attached to the
      left atrial wall. The mass was removed by open thoracic surgery and subsequently
      diagnosed as malignant diffuse large B-cell lymphoma with myxoma by
      histopathology. This was the fourth case of discovered Epstein-Barr virus
      positive diffuse large B-cell lymphoma in a cardiac myxoma reported so far. The
      patient has been well by followed up for 5 months without chemotherapy. Now we
      discuss the importance of histodiagnosis and the proper treatment. Epstein-Barr
      virus positive diffuse large B-cell lymphoma arising within atrial myxoma is an
      extraordinary lymphoma for better prognosis, avoiding excessive treatment. 

PMID- 25973120
TI  - Multfocal micronodular pneumocyte hyperplasia in a Chinese man masquerading as
      miliary tuberculosis.
AB  - Multifocal Micronodular Pneumocyte Hyperplasia (MMPH) is a rare and
      histologically, distinctive pulmonary manifestation of tuberous sclerosis complex
      (TSC) characterized by numerous and extensive proliferative lesions of type II
      pneumocytes similar to atypical adenomatous hyperplasia (AAH) or non-mucinous
      adenocarcinoma in situ (AIS). We reported MMPH in a 38-year-old Chinese man with
      TSC masquerading for 16 months as miliary tuberculosis and discussed the
      differential diagnosis. 

PMID- 25973121
TI  - Clear cell sarcoma of the pancreas: a case report and review of literature.
AB  - Clear cell sarcoma (CCS), is an uncommon malignant soft tissue neoplasm that
      displays melanocytic differentiation with a distinct molecular profile. It is
      very rarely localized in gastrointestinal tract. We reported the first case of a
      primary CCS arising in pancreas. A 36-year-old man presented with jaundice for
      one month. A preoperative abdominal computer tomography showed a low-density mass
      in the head of pancreas. Whipple procedure was performed and the tumor was
      resected. Pathological examination showed polygonal or fusiform cells arranged in
      a uniform nested to fascicular growth pattern with thin fibrous septa.
      Immunohistochemical studies revealed positivity for HMB-45, Melan A, S-100, MiTF
      and vimentin protein. Fluorescence in situ hybridization on paraffin section
      showed a translocation involving the EWSR1 gene region. No BRAF and NRAS mutation
      was detected. The patient underwent transcatheter arterial chemoembolization
      (TACE) six times and eventually died of diffuse liver metastasis 10 months later.
      This case illustrates that the pancreas is a potential site for primary clear
      cell sarcoma and molecular studies play an important role in making a conclusive
      diagnosis. 

PMID- 25973122
TI  - Basal cell adenoma of nasal septum: report of a case and review of literature.
AB  - Basal cell adenoma is an uncommon benign salivary gland neoplasm, presenting
      isomorphic basaloid cells with a prominent basal cell layer. Basal cell adenoma
      arising from the nasal septum is exceptionally rare. Reports on positron emission
      tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose (18FDG-PET) imaging for
      basal cell adenoma are limited. Here, we present the case of a 49-year-old man
      who had the symptoms of intermittent repeated bleeding from the left nose for
      half a year. 18FDG-PET scanning showed increased accumulation of 18FDG with its
      characteristic benign pathology has a potential to malignancy. After removal of
      the mass, the patient became symptom free. Pathology showed basal cell adenoma.
      The evidence of active and growing cells was present in the specimen.

PMID- 25973123
TI  - A giant mass on the left shin: report of a case.
AB  - A woman presented to our department with an asymptomatic progressive peripherally
      expanding skin lesion on her left shin for 6 years. The doctor in a local clinic
      considered it was a deep fungal infection, however, treatment with itraconazole
      systemically was ineffective. A second biopsy showed papillomatous hyperplasia
      and a central keratin-filled crater with a buttress like extension of surrounding
      epidermis and a well-demarcated regular base. In the upper dermis, diffused
      infiltration of mixed inflammatory cells was observed with perivascular
      infiltrate. Deeper dermis, appendageal structures and subcutaneous tissue were
      unremarkable. Periodic acid-schiffic staining and diamine silver staining of the
      specimen were negative. A diagnosis of Keratoacanthoma centrifugum marginatum
      (KCM) was finally established.

PMID- 25973124
TI  - Yolk sac tumor of vagina: a case report.
AB  - Malignant germ-cell tumors (MGCT) are rare tumors of childhood accounting for
      less than 3% of pediatric malignancies. Yolk sac (endodermal sinus) tumor is one
      of the malignant germ cell tumor that usually involves the gonads (ovaries and
      testes). Its occurrence in the vagina is extremely rare. We report a 6-months old
      girl presented with a vaginal mass diagnosed as a yolk sac tumor. This diagnosis
      is confirmed by histopathologic examination, immunehistochemical studies as well
      as elevated serum alpha fetoprotein (AFP). 

PMID- 25973125
TI  - Laparoscopic resection of intra-abdominal esophageal duplication cyst near
      spleen: a case report.
AB  - Esophageal duplication cysts (EDCs) are congenital malformations of the posterior
      primitive foregut and often within the thoracic esophagus. Here we describe a
      rare case of intra-abdominal EDC near spleen in a 20-year-old female patient with
      a complaint of an asymptomatic abdominal mass for 5 years. The diagnosis of intra
      abdominal EDC was confirmed by the Ultrasonography (US) and Magnetic resonance
      imaging (MRI) as well as Histological examination. Then the patient was received
      the laparoscopic resection and recovered well after the operation. We conclude
      that the laparoscopic resection is considered to be feasible and a reasonable
      treatment for intra-abdominal esophageal duplication cyst. 

PMID- 25973126
TI  - Subependymoma with extensive microcystic transformation: a case report.
AB  - Subependymomas are benign tumors that occur predominantly in the ventricular
      system. We described a case of a 44-year-old female with a large subtentorial
      mass which compressed the brain stem and fourth ventricle. Complete surgical
      excision of the tumor was achieved. The tumor composed of collections of
      cytologically bland cells with round to oval nuclei set within wide expanses of a
      delicate fibrillar matrix, and extensive microcystic changes were found. The
      tumor demonstrated positive staining with GFAP and S-100 protein, and did not
      stain with antibodies to Neu-N or Progesterone receptor, patchy expression of
      Epithelial Membrane Antigen. An MIB-1 labeling was lower than 1%. The tumor was
      totally resected and didn't recur after the initial surgery. 

PMID- 25973127
TI  - ALK-rearranged squamous cell lung cancer: a case report.
AB  - ALK rearrangement is a very rare subset of squamous cell cancer of lung and the
      efficacy of crizotinib treatment for these patients is lack of data. Here we
      report a case with squamous cell cancer of lung that harbored the ALK
      rearrangement was given crizotinib in the second-line therapy. A 55-year-old
      female patient was diagnosed with squamous cell carcinoma of lung by bronchoscopy
      biopsy with stage IV. The patient was given two cycles of chemotherapy and the
      response was progressive disease. After failure to chemotherapy, genotype testing
      showed wild-type EGFR/KRAS and ALK rearrangement positive. The patient was
      administered with crizotinib and had a partial response, and the progression-free
      survival was 6 months. The side effects were tolerable. 

PMID- 25973128
TI  - Primary hepatic malignant melanoma: a case report.
AB  - Primary hepatic malignant melanoma is a very rare disease. In order to provide
      clues concerning diagnosis, differential diagnosis and pathogenesis of the
      disease, a case of a 49 year-old female patient with primary hepatic malignant
      melanoma is presented. B-mode ultrasound and Contrast-enhanced abdominal
      computerized tomography (CT) examinations revealed that nodules of varying sizes
      are diffusely distributed in her enlarged liver. Pathological examination
      revealed that tumor cells with poor differentiation were located in nests with
      prominent melanin deposition. Immuno-histochemical staining showed that the tumor
      cells were positive for HMB-45 and S-100 protein. No evidence for primary
      malignant melanoma of other sites had been found by comprehensive examinations.
      Therefore, the patient was diagnosed with primary malignant melanoma of liver.
      Our case showed that primary malignant melanoma of liver is of histological
      heterogeneity, and immunohistochemical staining may aid in differential diagnosis
      between it and other hepatic neoplasms. 

PMID- 25973129
TI  - Primary costal myelolipoma: a case report and review of the literature.
AB  - Extra-adrenal myelolipoma is an uncommon entity. But myelolipoma located in the
      bone is extremely rare. We report a case of myelolipoma occurring in an unusual
      site: the Costa. It was demonstrated by Computed tomography (CT) scan that an
      expansive bony mass with heterogeneous low density contents adhered to the 6(th)
      ribs. The mass was successful resected and which was yielded to a bony lump
      through grossly inspection. Histological, the mass was confirmed as an
      intraosseous myelolipoma, with mature adipocytes mixed with hemopoietic cells. To
      the authors' knowledge, it is the first reported that myelolipoma located in the
      rib in human beings. 

PMID- 25973130
TI  - Primary sclerosing rhabdomyosarcoma of the scalp and skull: report of a case and
      review of literature.
AB  - We present a case of sclerosingrhabdomyosarcoma of the skull in a young male.
      This is a rare tumor that immunophenotypically shows rhabdomyoid differentiation.
      The lesion had a moderately aggressive course and the patient died at 19 months
      after diagnosis. 

PMID- 25973131
TI  - Anastomosing hemangioma arising from the kidney: a case of slow progression in
      four years and review of literature.
AB  - Reported herein is a renal anastomosing hemangioma which developed slowly in the
      past four years. A 25-year-old woman was found a mass localized in the upper
      portion four years ago, and only slow progression in the past four years. She
      underwent a laparoscopic partial nephrectomy of right kidney and diagnosed as
      anastomosing hemangioma. On histology the vascular components of the tumor had an
      anastomosing pattern without well-definite margins. Immunohistochemically, only
      endothelial markers (CD31, CD34) were expressed on the vascular components of
      tumor cells. Smooth muscle actin (SMA), cytokeratin (CK), EMA and S-100 and so on
      were all negative in the epithelioid tumor cells. The patient was alive at 16
      months after operation, without any evidence recurrence or metastasis.
      Anastomosing hemangioma is an extremely rare vascular neoplasm; only 23 cases
      were previously described until now. Our report of anastomosing hemangioma
      arising from the kidney with slow progression will improve the knowledge of
      primary vascular tumors arising in the kidney. 

PMID- 25973132
TI  - Inflammatory cytokine levels in patients with periodontitis and/or coronary heart
      disease.
AB  - The purpose of this study was to investigate systemic and local levels of four
      classic inflammatory cytokines (IL-1beta, MCP-1, VEGF, PDGF) in patients with
      periodontitis and coronary heart disease (CHD). 109 volunteers were enrolled and
      the condition of their periodontal tissue and coronary artery were assessed. The
      patients were then divided into four distinct groups: periodontitis only, CHD
      only, periodontitis with CHD, and healthy controls. Gingival crevicular fluid
      (GCF) and venous blood were collected. The concentrations of cytokines were
      detected meanwhile by specific ELISA. The IL-1beta and MCP-1 concentrations in
      the serum and GCF of the three disease groups were significantly higher than
      those in the control group (P <= 0.05). Serum VEGF concentrations of the patients
      with existing disease was lower than that of the controls. VEGF levels in the GCF
      of all disease groups were significantly higher than that of the control group (P
      <= 0.05). 

PMID- 25973133
TI  - Ultrasound-mediated microbubble destruction enhances the therapeutic effect of
      intracoronary transplantation of bone marrow stem cells on myocardial infarction.
AB  - OBJECTIVE: The combination of intracoronary transplantation and ultrasound
      mediated microbubble destruction may promote effective and accurate delivery of
      bone marrow stem cells (BMSCs) into the infarct zone. To test this hypothesis in
      this study we examined the effectiveness of ultrasound-mediated microbubble
      destruction in combination with intracoronary transplantation of BMSCs for the
      treatment of myocardial infarction in canine model of acute myocardial
      infarction. METHOD: The dogs were randomly assigned to four groups: PBS,
      ultrasound-mediated microbubble destruction, BMSCs, BMSCs together with
      ultrasound-mediated microbubble destruction. At 28 days post-surgery, cardiac
      function and the percentage of perfusion defect area to total left ventricular
      perfusion area (DA%) were determined by myocardial contrast echocardiography.
      Nitro blue tetrazolium staining was performed to determine myocardial infarct
      size, hematoxylin and eosin staining for assessing microvascular injury, Masson's
      staining for analyzing myocardial tissue collagen, immunohistochemical analysis
      of alpha-actin to measure cardiac contractile function and of BrdU-labeled
      myocardial cells to measure the number of the BMSCs homing to the infarcted
      region. RESULTS: The transplantation of BMSCs significantly improved heart
      function and DA% (P < 0.05). The group that received ultrasound-mediated
      microbubble destruction with BMSCs transplantation showed the most improvement in
      heart function and DA% (P < 0.05). This group also showed a denser deposition of
      BMSCs in the coronary artery and more BrdU positive cells in the infarcted
      region, had the maximum number of alpha-actin positive cells, showed the smallest
      myocardial infarct area compared to other groups (P< 0.05). CONCLUSION:
      Ultrasound-mediated microbubble destruction increases the homing of BMSCs in the
      target area following intracoronary transplantation, which allows more BMSCs to
      differentiate into functional cardiomyocytes, thereby reducing myocardial infarct
      size and improving cardiac function.

PMID- 25973134
TI  - Inhibition of ovarian cancer proliferation and invasion by pachymic acid.
AB  - To determine the effect of pachymic acid (PA) on proliferation, cell cycle, and
      invasion in human ovarian carcinoma cell lines HO-8910 and explore some possible
      mechanisms, HO-8910 cells was treated with different concentrations of PA (0.5,
      1, 2 MUM). CCK-8 assay, propidium iodide staining, was applied to measuring the
      growth inhibiting rates of HO-8910 cells. Cell cycle was measured by flow
      cytometry. In addition, the activity of PA against HO-8910 cells invasion was
      evaluated in transwell assay. Western blot detected the proteins expression of E
      cadherin, beta-catenin and COX-2 of different groups treated with PA in different
      concentrations (0.5, 1, 2 MUM) for 48 h. Our results showed that PA could
      effectively inhibit the in vitro growth of HO-8910 cells in dose-dependent
      manners in 72 h, suppressed migration and invasion of HO-8910 cells in
      concentration-dependent manners at 24 h, caused the increased accumulation of G1
      phase cells, and caused down-regulation of beta-catenin and COX-2 and up
      regulation of E-cadherin expression level. Taken together, it could conclude that
      PA might inhibit proliferation and invasion of ovarian carcinoma cell through
      decreasing beta-catenin and COX-2 expression and increasing E-cadherin
      expression.

PMID- 25973135
TI  - Establishment of rat pneumococcal meningitis models: a histopathological
      analysis.
AB  - The aim of this study was to perform a preliminary investigation of the
      pathogenesis of bacterial meningitis-induced brain injury by establishing rat
      pneumococcal meningitis models. Infant Wistar rats were intracranially inoculated
      with different concentrations of Streptococcus pneumoniae. Rats were sacrificed
      at different time points to observe clinical symptoms and pathological changes in
      brain tissues. Twenty-four hours after intracranial inoculation with
      Streptococcus pneumoniae, regardless of high or low concentrations of bacterial
      inoculation, all rats developed bacterial meningitis with manifestations such as
      lethargy and seizures. Pathological changes in brain tissues included
      subarachnoid and intraventricular inflammation, vasodilation and vascular
      congestion, and cortical neuronal necrosis. The number of rats with seizures, the
      degree of cerebral vascular disease, and the extent of neuronal damage were
      associated with the concentration of bacterial inoculum. Thirty days after
      infection, brain tissue weight significantly reduced. The pathological changes
      induced by inoculation with pneumococcal meningitis in Wistar rats were similar
      to those seen in the human brain. The possible mechanisms of brain damage caused
      by meningitis are cerebrovascular inflammation and disruption of regional
      cerebral blood flow. 

PMID- 25973136
TI  - RANK overexpression as a novel esophageal cancer marker: validated
      immunohistochemical analysis of two different ethnicities.
AB  - This study aimed to evaluate the receptor activator of nuclear factor-kappaB
      (RANK) expression statuses of esophageal squamous cell carcinoma (ESCC) patients,
      high-grade intraepithelial neoplasia (HGIN), low-grade intraepithelial neoplasia
      (LGIN), and normal esophageal tissues (NETs) in Chinese Han and Kazakh ethnic, as
      well as the correlation of RANK expression with clinicopathological
      characteristics. RANK immunohistochemical analysis was conducted to investigate
      the expression of RANK in 113 ESCC, 36 HGIN, 63 LGIN, and 98 NETs from Han ethnic
      patients and in 196 ESCC and 76 NETs from Kazakh ethnic patients. The
      associations of RANK expression with ethnic and clinicopathological
      characteristics were examined using chi(2)-test. Upregulated RANK expression was
      detected in both Han and Kazakh ethnic ESCC tissues, compared with NETs (P = 1.11
      * 10(-5), 0.001, respectively). RANK expression was significantly increased
      during malignant transformation from normal epithelium into LGIN (P = 2.84 * 10(
      7)) and HGIN (P = 7.83 * 10(-6)) tissues in Han ethnic patients. The increased
      expression of RANK also correlated with lymph node metastasis in Kazakh ethnic
      ESCC patients (P = 0.019). By contrast, no significant correlation existed
      between RANK expression and clinicopathological characteristics of Han ethnic
      ESCC patients. Furthermore, Kaplan-Meier survival analysis showed that ESCC
      patients with higher expression of RANK protein had significantly worse prognosis
      than ESCC patients with low or no expression (P = 0.001). In conclusion, this
      study is the first to identify RANK overexpression as a novel esophageal cancer
      marker in both Kazakh and Han ethnic ESCC patients. The results support the
      association of RANK with ESCC across ethnicities. In summary, RANK could be a
      therapeutic target in ESCC patients.

PMID- 25973138
TI  - Real-world data confirm clinical trial outcomes for rivaroxaban in orthopaedic
      patients.
AB  - Venous thromboembolism (VTE) is a potential cause of morbidity and mortality in
      patients after major orthopaedic surgery. Based on the results of the
      international phase III RECORD (Regulation of Coagulation in Orthopaedic Surgery
      to Prevent Deep Vein Thrombosis and Pulmonary Embolism) program, the oral, direct
      Factor Xa inhibitor rivaroxaban has been approved in many countries for the
      prevention of VTE after elective hip arthroplasty or knee arthroplasty. However,
      study results of randomized controlled trials may have limited generalizability
      to routine clinical practice in unselected patients. The phase IV XAMOS
      (Xarelto(r) in the Prophylaxis of Postsurgical Venous Throboembolism after
      Elective Major Orthopaedic Surgery of the Hip or Knee) study and the ORTHO-TEP
      (large single-center registry) collected real-world data to assess the
      effectiveness and safety of rivaroxaban compared with standard of care in large
      cohorts of patients undergoing major orthopaedic surgery. This review evaluates
      real-world data from XAMOS and ORTHO-TEP, confirming the favorable benefit-risk
      profile of rivaroxaban for the prevention of VTE in patients after major
      orthopaedic surgery that was demonstrated by the phase III RECORD studies in
      patients after elective hip or knee arthroplasty.

PMID- 25973137
TI  - miR-27a promotes cell proliferation and metastasis in renal cell carcinoma.
AB  - miR-27a has been reported to exhibit abnormal expression in renal cell carcinoma
      (RCC), but the role of miR-27a in RCC remains unknown. In our study, up
      regulation of miR-27a was validated by Real-time PCR analysis in 133 RCC samples.
      Overexpression of miR-27a promoted cell migration, invasion and proliferation in
      vitro, while its low expression exerted opposite effects. Kaplan-Meier analysis
      demonstrated that the patients with high expression of miR-27a had a worse
      overall and relapse-free survivals compared with those with low expression of miR
      27a. Cox proportional hazards analyses showed that miR-27a expression was an
      independent prognostic factor for RCC patients. Collectively, our findings
      illustrate the promoting-cancer effect of miR-27a in RCC, suggesting that miR-27a
      could be a potential therapeutic target for RCC. Additionally, Kaplan-Meier
      analyses and Cox proportional regression analysis suggest that miR-27a may be a
      potential biomarker for predicting the survival of RCC patients. 

PMID- 25973139
TI  - Alzheimer's pathogenesis and its link to the mitochondrion.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly. This
      neurodegenerative disorder is clinically characterized by impairment of cognitive
      functions and changes in behaviour and personality. The pathogenesis of AD is
      still unclear. Recent evidence supports some role of mitochondria dysfunction and
      oxidative stress in the development of the neurodegenerative process. In this
      review, we discuss the role of mitochondrial dysfunction in AD, focusing on the
      mechanisms that lead to mitochondrial impairment, oxidative stress, and
      neurodegeneration, a "vicious circle" that ends in dementia. 

PMID- 25973141
TI  - Actions of adenosine on cullin neddylation: implications for inflammatory
      responses.
AB  - There is intense interest in understanding how the purine nucleoside adenosine
      functions in health and during disease. In this review, we outline some of the
      evidence that implicates adenosine signaling as an important metabolic signature
      to promote inflammatory resolution. Studies derived from cultured cell systems,
      animal models and human patients have revealed that nucleotide metabolism is
      significant component of the overall inflammatory microenvironment. These studies
      have revealed a prominent role for the transcription factors NF-kappaB and
      hypoxia-inducible factor (HIF) and that these molecules are post-translationally
      regulated through similar components, namely the neddylation of cullins within
      the E3 ligase that are controlled through adenosine receptor signaling. Studies
      defining differences and similarities between these responses have taught us a
      number of important lessons about the complexity of the inflammatory response. A
      clearer definition of these pathways has provided new insight into disease
      pathogenesis and importantly, the potential for new therapeutic targets. 

PMID- 25973140
TI  - Oxidative Stress during the Progression of beta-Amyloid Pathology in the
      Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia, characterized by
      progressive neurodegeneration. Pathogenetic mechanisms, triggered by beta-amyloid
      (Abeta) accumulation, include oxidative stress, derived from energy homeostasis
      deregulation and involving mitochondria and peroxisomes. We here addressed the
      oxidative stress status and the elicited cellular response at the onset and
      during the progression of Abeta pathology, studying the neocortex of Tg2576 model
      of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes,
      and related transcription factors were analysed in relation to the distribution
      of Abeta peptide and oligomers, by a combined molecular/morphological approach.
      Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and
      decreased PGC1alpha expression are already detected in 3-month-old Tg2576
      neurons. Conversely, PPARalpha is increased in these cells, with its cytoplasmic
      localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when
      intracellular Abeta accumulates, PMP70 is downregulated, indicating impairment of
      fatty acids peroxisomal translocation and their consequent harmful accumulation.
      In 9-month-old Tg2576 neocortex, Abeta oligomers and acrolein deposition
      correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory
      response, involving astroglial peroxisomes. At severe pathological stages, when
      senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is
      gradually lost. Overall, our data suggest early therapeutic intervention in AD,
      also targeting peroxisomes. 

PMID- 25973142
TI  - John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors.
AB  - We establish structure activity relationships of extracellular nucleosides and
      nucleotides at G protein-coupled receptors (GPCRs), e.g. adenosine receptors
      (ARs) and P2Y receptors (P2YRs), respectively. We synthesize selective agents for
      use as pharmacological probes and potential therapeutic agents (e.g. A3AR
      agonists for neuropathic pain). Detailed structural information derived from the
      X-ray crystallographic structures within these families enables the design of
      novel ligands, guides modification of known agonists and antagonists, and helps
      predict polypharmacology. Structures were recently reported for the P2Y12
      receptor (P2Y12R), an anti-thrombotic target. Comparison of agonist-bound and
      antagonist-bound P2Y12R indicates unprecedented structural plasticity in the
      outer portions of the transmembrane (TM) domains and the extracellular loops.
      Nonphosphate-containing ligands of the P2YRs, such as the selective P2Y14R
      antagonist PPTN, are desired for bioavailability and increased stability. Also,
      A2AAR structures are effectively applied to homology modeling of closely related
      A1AR and A3AR, which are not yet crystallized. Conformational constraint of
      normally flexible ribose with bicyclic analogues increased the ligand
      selectivity. Comparison of rigid A3AR agonist congeners allows the exploration of
      interaction of specific regions of the nucleoside analogues with the target and
      off-target GPCRs, such as biogenic amine receptors. Molecular modeling predicts
      plasticity of the A3AR at TM2 to accommodate highly rigidified ligands. Novel
      fluorescent derivatives of high affinity GPCR ligands are useful tool compounds
      for characterization of receptors and their oligomeric assemblies. Fluorescent
      probes are useful for characterization of GPCRs in living cells by flow cytometry
      and other methods. Thus, 3D knowledge of receptor binding and activation
      facilitates drug discovery. 

PMID- 25973143
TI  - Comparison of Metabolic Pathways in Escherichia coli by Using Genetic Algorithms.
AB  - In order to understand how cellular metabolism has taken its modern form, the
      conservation and variations between metabolic pathways were evaluated by using a
      genetic algorithm (GA). The GA approach considered information on the complete
      metabolism of the bacterium Escherichia coli K-12, as deposited in the KEGG
      database, and the enzymes belonging to a particular pathway were transformed into
      enzymatic step sequences by using the breadth-first search algorithm. These
      sequences represent contiguous enzymes linked to each other, based on their
      catalytic activities as they are encoded in the Enzyme Commission numbers. In a
      posterior step, these sequences were compared using a GA in an all-against-all
      (pairwise comparisons) approach. Individual reactions were chosen based on their
      measure of fitness to act as parents of offspring, which constitute the new
      generation. The sequences compared were used to construct a similarity matrix (of
      fitness values) that was then considered to be clustered by using a k-medoids
      algorithm. A total of 34 clusters of conserved reactions were obtained, and their
      sequences were finally aligned with a multiple-sequence alignment GA optimized to
      align all the reaction sequences included in each group or cluster. From these
      comparisons, maps associated with the metabolism of similar compounds also
      contained similar enzymatic step sequences, reinforcing the Patchwork Model for
      the evolution of metabolism in E. coli K-12, an observation that can be expanded
      to other organisms, for which there is metabolism information. Finally, our
      mapping of these reactions is discussed, with illustrations from a particular
      case. 

PMID- 25973144
TI  - Under-detection of endospore-forming Firmicutes in metagenomic data.
AB  - Microbial diversity studies based on metagenomic sequencing have greatly enhanced
      our knowledge of the microbial world. However, one caveat is the fact that not
      all microorganisms are equally well detected, questioning the universality of
      this approach. Firmicutes are known to be a dominant bacterial group. Several
      Firmicutes species are endospore formers and this property makes them hardy in
      potentially harsh conditions, and thus likely to be present in a wide variety of
      environments, even as residents and not functional players. While metagenomic
      libraries can be expected to contain endospore formers, endospores are known to
      be resilient to many traditional methods of DNA isolation and thus potentially
      undetectable. In this study we evaluated the representation of endospore-forming
      Firmicutes in 73 published metagenomic datasets using two molecular markers
      unique to this bacterial group (spo0A and gpr). Both markers were notably absent
      in well-known habitats of Firmicutes such as soil, with spo0A found only in three
      mammalian gut microbiomes. A tailored DNA extraction method resulted in the
      detection of a large diversity of endospore-formers in amplicon sequencing of the
      16S rRNA and spo0A genes. However, shotgun classification was still poor with
      only a minor fraction of the community assigned to Firmicutes. Thus, removing a
      specific bias in a molecular workflow improves detection in amplicon sequencing,
      but it was insufficient to overcome the limitations for detecting endospore
      forming Firmicutes in whole-genome metagenomics. In conclusion, this study
      highlights the importance of understanding the specific methodological biases
      that can contribute to improve the universality of metagenomic approaches. 

PMID- 25973145
TI  - Identification of miRNAs contributing to neuroblastoma chemoresistance.
AB  - BACKGROUND: The emergence of the role of microRNAs (miRNAs) in exacerbating drug
      resistance of tumours is recently being highlighted as a crucial research field
      for future clinical management of drug resistant tumours. The purpose of this
      study was to identify dys-regulations in expression of individual and/or networks
      of miRNAs that may have direct effect on neuroblastoma (NB) drug resistance.
      METHODS: Individual subcultures of chemosensitive SH-SY5Y and UKF-NB-3 cells were
      rendered chemoresistant to doxorubicin (SH-SY5Y, UKF-NB-3) or etoposide (SH
      SY5Y). In each validated chemoresistance model, the parental and subcultured cell
      lines were analysed for miRNA expression profiling, using a high-throughput
      quantitative polymerase chain reaction (RT-qPCR) miRNA profiling platform for a
      total of 668 miRNAs. RESULTS: A unique expression signature of miRNAs was found
      to be differentially expressed (higher than 2-fold change) within all three NB
      chemoresistance models. Four miRNAs were upregulated in the subcultured
      chemoresistant cell line. Three miRNAs were found to be downregulated in the
      chemoresistant cell lines for all models. CONCLUSIONS: Based on the initial miRNA
      findings, this study elucidates the dys-regulation of four miRNAs in three
      separate NB chemoresistant cell line models, spanning two cell lines (SH-SY5Y and
      UKF-NB-3) and two chemotherapeutic agents (doxorubicin and etoposide). These
      miRNAs may thus be possibly linked to chemoresistance induction in NB. Such
      miRNAs are good candidates to be novel drug targets for future miRNA based
      therapies against aggressive tumours that are not responding to conventional
      chemotherapy.

PMID- 25973146
TI  - The effect of different concentrations of chlorhexidine gluconate on the
      compressive strength of mineral trioxide aggregate.
AB  - Background and aims. Substituting chlorhexidine (CHX) for water has been shown to
      enhance antimicrobial activity of mineral trioxide aggregate (MTA). The purpose
      of this study was to compare the compressive strength of MTA mixed with distilled
      water, 0.12% and 0.2% chlorhexidine. Materials and methods. MTA was mixed
      according to manufacturer's instructions in group I (n = 20). In groups II & III,
      0.12% and 0.2% CHX liquid was substituted for water, respectively. Samples were
      condensed with moderate force into 20 tubes with 1.5*5 mm dimensions and were
      allowed to set for 72 hours at 37 degrees C in 100% humidity. After being removed
      from the molds, their compressive strength was determined using Instron testing
      machine. Each group was divided into two subgroups according to the time of
      testing (at 72 hours, and one week). Fractured surfaces of 4 specimens in each
      group were then evaluated under Scanning Electron Microscope (SEM) to determine
      their microstructure. One-way ANOVA, Tukey, and paired sample t-test was used for
      statistical analysis. P < 0.05 was set as significant. Results. There was no
      significant difference between three groups in terms of their compressive
      strength after 72 hours. However, the compressive strength of group II was
      significantly higher than group I (P = 0.034) and group III (P = 0.021) after one
      week. Crystalline microstructure was similar in all groups. Conclusion.
      Substitution of 0.012% chlorhexidine for water significantly increased the
      compressive strength of MTA at 1 week without significant change in crystalline
      structure. 

PMID- 25973147
TI  - The Effect of Thickness on the Sealing Ability of CEM Cement as a Root-end
      Filling Material.
AB  - Background and aims. Different materials have been used for root-end filling
      during surgical endodontic treatment. The aim of this in vitro study was to
      evaluate the dye penetration in different thicknesses of calcium enriched mixture
      (CEM) cement as root-end filling material. Materials and methods. Following root
      canal filling in 70 extracted human single-rooted premolar teeth, the apical 3 mm
      of their root-ends was resected; the root-end cavities with depths of 1, 2 and 3
      mm were prepared by ultrasonic retrotips and filled with CEM cement. After
      setting of cement, the roots were immersed in 2% Rhodamine B and the dye leakage
      was measured under stereomicroscope (*16) using Image J software. The data were
      analyzed by one-way ANOVA and Bonferroni post hoc tests at 5% significance level.
      Results. The means and standard deviations of dye penetration in the 1, 2, and 3
      mm groups were 3395.5+/-1893.4, 3410.4+/-1440.5, and 2581.6+/-1852.9 MUm,
      respectively. The one-way ANOVA analysis indicated significant differences (P <
      0.001); however, the Bonferroni post hoc test revealed that only the positive
      control group differed significantly from the experimental groups (P < 0.001).
      Conclusion. The findings demonstrated CEM cement to have an adequate root-end
      sealing ability in 3-mm thickness. 

PMID- 25973148
TI  - Effect of Non-surgical Periodontal Therapy on Serum and Salivary Concentrations
      of Visfatin in Patients with Chronic Periodontitis.
AB  - Background and aims. Visfatin, mainly secreted by visceral adipose tissue,
      especially by macrophages, plays an important role in regulating the defense and
      immune functions, and functions as a growth factor, a cytokine, an enzyme and
      more importantly as a proinflammatory mediator. The aim of the present study was
      to evaluate the effect of non-surgical periodontal treatment on serum and
      salivary levels of visfatin in patients with generalized moderate-to-severe
      chronic periodontitis. Materials and methods. Eighteen patients with generalized
      moderate-to-severe chronic periodontitis were selected based on periodontal
      parameters of gingival index (GI), probing pocket depth (PPD), clinical
      attachment level (CAL) and radiographic parameters. Serum and salivary samples
      were collected at baseline and one month following non-surgical periodontal
      therapy (scaling and root planing ([SRP]). Visfatin levels were measured using an
      ELISA kit. Data were analyzed by SPSS 15, using paired t-test and Pearson's
      correlation coefficient. Results. Mean salivary and serum levels of visfatin
      significantly decreased after non-surgical periodontal treatment (P<0.05).
      Changes in salivary visfatin levels were more prominent. Conclusion. According to
      the findings of this study it seems that there is a direct relationship between
      periodontal tissue inflammation and disease activity with salivary and serum
      visfatin levels. 

PMID- 25973149
TI  - Diagnostic Accuracy of Charge-coupled Device Sensor and Photostimulable Phosphor
      Plate Receptor in the Detection of External Root Resorption In Vitro.
AB  - Background and aims. Early diagnosis of external root resorption is important for
      accurate treatment. The purpose of this study was to compare the efficacy of a
      charge-coupled device (CCD) sensor and a photostimulable phosphor (PSP) plate
      receptor in the diagnosis of artificial external root resorption. Materials and
      methods. In this diagnostic in-vitro study, 40 maxillary incisors were mounted in
      a segment of dry bone and preliminary radiographs were obtained using CCD and PSP
      sensors. Artificial resorption cavities were produced on the middle-third in half
      of the samples and on the cervical-third in the other half on the buccal root
      surfaces. Radiographs were repeated and images were evaluated. Data were
      statistically analyzed using chi-square and diagnostic tests. Results. There were
      no significant differences between the two sensors in the sensitivity (p=0.08 and
      0.06) and specificity (p=0.13) for the diagnosis of resorption in both root
      areas. The overall accuracy of CCD was higher than PSP sensor; however, the
      difference was not statistically significance (p>0.05). Conclusion. CCD and PSP
      sensors chosen for the present study produced similar results in diagnosing
      simulated external root resorption. 

PMID- 25973151
TI  - Immunohistochemichal Assessment of the CrkII Proto-oncogene Expression in Common
      Malignant Salivary Gland Tumors and Pleomorphic Adenoma.
AB  - Background and aims. Various morphologies are seen in different salivary gland
      tumorsor within an individual tumor, and the lesions show divers biological
      behaviors. Experimental results support the hypothesis that increased CrkII proto
      oncogene is associated with cytokine-induced tumor initiation and progression by
      altering cell motility signaling pathway. The aim of this study was to assess the
      CrkII expression in common malignant salivary gland tumors and pleomorphic ade
      noma. Materials and methods. Immunohistochemical analysis of CrkII expression was
      performed on paraffin blocks of 64 car-cinomas of salivary glands, 10 pleomorphic
      adenomas, and 10 normal salivary glands. Biopsies were subjected to immu
      nostaining with EnVision detection system using monoclonal anti-CrkII. Evaluation
      of immunoreactivity of CrkII was based on the immunoreaction intensity and
      percentage of stained tumor cells which were scored semi-quantitatively on a
      scale with four grades 0 to 3. Kruskal-wallis test and additional Mann-Whitney
      statistical test were used for analysis of CrkII expression levels. Results.
      Increased expression of CrkII was seen (P=0.005) in malignant tumors including:
      mucoepidermoid carcinoma, adenoid cystic carcinoma, and carcinoma ex pleomorphic
      adenoma, but CrkII expression in acinic cell carcinoma was weak. CrkII expression
      in pleomorphic adenoma was weak or negative. A weak staining was sparsely seen in
      normal acinar serous cell. Conclusion. Increased expression of CrkII and its
      higher intensity of staining in tumors with more aggressive biologic behavior in
      carcinomas of salivary gland is consistent with a role for this proto-oncogene in
      salivary gland tumorigenesis and cancer progression. 

PMID- 25973150
TI  - A Randomized Placebo-controlled Double Blind Clinical Trial of Quercetin for
      Treatment of Oral Lichen Planus.
AB  - Background and aims. Standard treatment of oral lichen planus (OLP) includes
      topical or systemic corticosteroids that have many adverse effects. A trend
      toward alternative natural or herbal drugs has attended recently. This study was
      conducted to evaluate the effect of quercetin in treatment of erosive-atrophic
      OLP. Materials and methods. Thirty patients participated in this randomized
      clinical trial from April 2010 to June 2010 (TRIAL REGISTRATION NUMBER:
      NCT01375101). Patients were randomly allocated in two groups. Both groups
      received the standard treatment (dexamethasone mouthwash and nystatin
      suspension). Experimental group received oral 250 mg quercetin hydrate capsules
      (bid) and the control group received placebo capsules. The pain and severity of
      the lesions were recorded at the initial visit and the follow-ups. All recorded
      data were analyzed with chi-square, Mann-Whitney, t-test, Wilcoxon and Friedman
      tests using SPSS 11.5. Results. There were no significant differences between the
      two groups in severity of the lesions and pain in the follow-ups.According to the
      Friedman test, there was a significant reduction in pain (P = 0.01) and severity
      indices (P = 0.00) in the case group. These differences were not observed in the
      control group(P = 0.26,SI; and P = 0.86, PI). No adverse effect of quercetin was
      reported. Conclusion. According to the results, no significant therapeutic effect
      can be considered for quercetin in treatment of OLP. 

PMID- 25973152
TI  - Evaluation of the Effect of Axial Wall Modification and Coping Design on the
      Retention of Cement-retained Implant-supported Crowns.
AB  - Background and aims. Because of compromised angulations of implants, the
      abutments are sometimes prepared. The purpose of this study was to investigate
      the effect of removing one wall of the implant abutment on the retention of
      cement-retained crowns. Materials and methods. Four prefabricated abutments were
      attached to analogues and embedded in acrylic resin blocks. The first abutment
      was left intact. Axial walls were partially removed from the remaining abutments
      to produce abutments with three walls. The screw access channel for the first and
      second abutments were completely filled with composite resin. For the third and
      fourth abutments, only partial filling was done. Wax-up models were made by
      CAD/CAM. Ten cast copings were fabricated for each abutment. The copings of
      fourth abutment had an extension into the screw access channel. Copings were
      cemented with Temp Bond. The castings were removed from the abutment using an
      Instron machine, and the peak removal force was recorded. A one-way ANOVA was
      used to test for a significant difference followed by the pairwise comparisons.
      Results. The abutments with opened screw access channel had a significantly
      higher retention than the two other abutments. The abutment with removed wall and
      no engagement into the hole by the castings exhibited the highest retention.
      Conclusion. Preserving the opening of screw access channel significantly
      increases the retention where one of the axial walls of implant abutments for
      cement-retained restorations is removed during preparation. 

PMID- 25973153
TI  - Effect of Silver Nano-particles on Tensile Strength of Acrylic Resins.
AB  - Background and aims. Polymethyl methacrylate (PMMA) is widely used for the
      fabrication of removable prostheses. Silver nano-particles (AgNps) have been
      added to PMMA because of their antimicrobial properties, but their effect on the
      mechanical properties of PMMA is unknown. The aim of this study was to
      investigate the effects of AgNps on the tensile strength of PMMA. Materials and
      methods. For this study, 12 specimens were prepared and divided into two groups.
      Group 1 included PMMA without AgNps and group 2 included PMMA mixed with 5 wt% of
      AgNps. Tensile strength of the specimens was measured by Zwick Z100 apparatus.
      Statistical analysis was carried out by SPSS using t-test. Statistical
      significance was defined at P<0.05. Results. This study showed that the mean
      tensile strength of PMMA in group 2 was significantly lower than that in group 1.
      Therefore, the tensile strength decreased significantly after incorporation of
      silver nano-particles. CONCLUSION: Within the limitations of this study, tensile
      strength of acrylic resin specimens was influenced by silver nano-particles.

PMID- 25973154
TI  - Cariostatic effect of green tea in comparison with common anticariogenic agents:
      an in vitro study.
AB  - Background and aims. Anticariogenic effects of different mouthrinses have been
      shown previously. In this in vitro study the anticariogenic effects of polyphenol
      extract of green tea with 0.05% fluoride, 0.2% chlorhexidine and fluoride
      chlorhexidine were compared. Materials and methods. This in vitro study was
      performed on 50 maxillary premolars in 5 groups: 1) normal saline; 2) a 10%
      solution of green tea polyphenol extract; 3) 0.05% fluoride; 4) 0.2%
      chlorhexidine; and 5) fluoride-chlorhexidine. Each tooth was placed in a tube
      which contained a cariogenic solution. Every day the teeth were washed (depending
      on the experimental groups) with 5 mL of mouthrinse solution. The depth of the
      caries was measured under a polarized light microscope. Data were analyzed using
      SPSS 13.0 with Kolmogorov-Smirnov, one-way ANOVA and Tukey tests. Results. The
      mean and standard deviation (in um) of caries depth were 194+/-16.43, 175+/
      17.94, 142+/-9.34, 155+/-13.27, and 144+/-8.57 in groups 1 to 5, respectively,
      with significant differences between the groups (P<0.001). Tukey test showed that
      although there was no significant difference in the depth of caries in groups 1
      and 2 (P>0.001), they were significantlyless than those in groups 3 to 5
      (P<0.001). There was no significant difference between decay depth of groups 3, 4
      and 5 (P>0.001). Conclusion. The anticariogenic effect of fluoride-chlorhexidine
      was the highest among the groups. Although green tea showed higher cariostatic
      effects than normal saline, in comparison with other mouthrinses, it is less
      effective. More re-search is strongly recommended for clinical use of green tea
      as an anticariogenic agent. 

PMID- 25973155
TI  - Effect of Fluoride, Chlorhexidine and Fluoride-chlorhexidine Mouthwashes on
      Salivary Streptococcus mutans Count and the Prevalence of Oral Side Effects.
AB  - Background and aims. Streptococcus mutans is the main pathogenic agent involved
      in dental caries, and may be eliminated using mouthwashes. The objective of this
      study was to compare the effects of fluoride, chlorhexidine, and fluoride
      chlorhexidine mouthwashes on salivary S. mutans count after two weeks of use and
      determine the prevalence of their side effects on the oral mucosa. Materials and
      methods. In this clinical trial, 120 12-14 year-old students were selected and
      divided into three groups. Each group was given one of fluoride, chlorhexidine,
      or fluoride-chlorhexidine mouthwashes. They were asked to use it twice a day for
      two weeks. Salivary samples were collected at baseline and after two weeks. Data
      were analyzed by Wilcoxon and Kruskal-Wallis tests. Results. In all the study
      groups, there were statistically significant reductions in salivary S. mutans
      counts two weeks after using the mouthwashes (P < 0.05). In addition, fluoride
      chlorhexidine mouthwash had a significant effect on the reduction of S. mutans
      count in comparison with fluoride alone. The prevalence of oral side effects in
      fluoride-chlorhexidine mouth-wash was more than 90%. Conclusion. Adding fluoride
      to chlorhexidine mouthwash can significantly decrease salivary S. mutans count
      after two weeks. Fluoride-chlorhexidine has the highest rate of oral side effects
      between the evaluated mouthwash compounds. 

PMID- 25973156
TI  - Treatment of Long-standing Condylar Dislocation with Vertical Ramus Osteotomy: A
      Case Report.
AB  - Condylar dislocation is not an uncommon condition and occurs when the condyles
      are displaced anterior to the articular eminence and are unable to reduce back
      into the glenoid fossa. Long-standing dislocations are difficult to treat with
      the conservative methods and usually need surgical intervention. In this paper, a
      long-standing dislocation treated by bilateral extra-oral ramus osteotomy is
      described and the literature is reviewed. 

PMID- 25973157
TI  - Root canal treatment of a hypertaurodont mandibular second molar: a case report.
AB  - Taurodontism is a morphologic feature of generally multi-rooted teeth with large
      pulp chambers and shortened roots. A case of endodontic treatment in a 24-year
      old male with the chief complaint of swelling and pain in the right mandibular
      region is described. Periapical lesion was present in the radiographic
      examination of hypertaurodont second mandibular molar.Four root canals were
      detected with an endodontic microscope. The canals were prepared and obturated
      with lateral condensation technique in the second appointment. The patient was
      asymptomatic in the 18-month follow-up. 

PMID- 25973158
TI  - Bioactivity of Apium petroselinum and Portulaca oleracea Essential Oils as
      Natural Preservatives.

PMID- 25973159
TI  - Determining the Role of Helicobacter pylori in Chronic Sinus Infections Using the
      Polymerase Chain Reaction.
AB  - BACKGROUND: Helicobacter pylori are becoming increasingly recognized as a
      possible pathological cause of chronic rhinosinusitis (CRS). OBJECTIVES:
      Considering the prevalence of CRS and its impact on quality of life, we decided
      to determine the role of H. pylori in chronic sinus infections by using the PCR
      technique. PATIENTS AND METHODS: In a case-control analytical epidemiologic
      survey, the study population was selected by consecutive sampling from patients
      with CRS undergoing endoscopic sinus surgery during years 2010 - 2012. Patients
      were divided into two groups. The study group consisted of patients with CRS and
      the control group consisted of patients with nasal obstruction caused by concha
      bullosa, without inflammation or infection of the sinuses. Sampling was performed
      during surgery from the infected tissue and from the middle turbinate mucosa.
      Eventually, bacterial DNA was extracted and used for the PCR test, in order to
      isolate H. pylori. RESULTS: Nine patients (18%) with CRS had H. pylori isolated
      from their samples whereas in the control group, H. pylori were only found in two
      patients (4%); this difference was statistically significant (P = 0.025). The
      indicator wasn't statistically significant between males and females. There was
      no statistical correlation in relative frequency of H. pylori for different age
      groups (P > 0.05). CONCLUSIONS: There was a significant correlation between CRS
      and presence of H. pylori in sinonasal mucosa. This relationship may reflect the
      role of H. pylori as one of the pathogenic factors in the development of CRS.
      However, further studies are required to confirm this role.

PMID- 25973160
TI  - Comparison of Serum Hepatitis B Virus DNA and HBsAg Levels Between HBeAg-Negative
      and HBeAg-Positive Chronic Hepatitis B Patients.
AB  - BACKGROUND: Chronic hepatitis B consists of different clinical phases. Laboratory
      and histological assessments can help differentiate the clinical phases of this
      disease and thus lead to better management. OBJECTIVES: This study was conducted
      to determine laboratory and histological characteristics of HBeAg-negative and
      HBeAg-positive chronic hepatitis B patients. PATIENTS AND METHODS: In this study,
      we evaluated 151 treatment naive chronic hepatitis B patients and grouped them
      according to their HBeAg status. Serum hepatitis B virus (HBV) DNA and HBsAg
      levels were measured, and liver function tests, and liver biopsy were performed
      for the study population. RESULTS: There was a significant difference in age, and
      HBV DNA and HBsAg levels between HBeAg-negative and HBeAg-positive groups yet
      there was no statistically significant difference in sex, liver function tests,
      grading and staging of liver biopsy between the groups. Hepatitis B virus DNA and
      HBsAg levels were correlated in both HBeAg-negative and HBeAg-positive chronic
      hepatitis B patients. CONCLUSIONS: We concluded that chronic hepatitis B patients
      had different HBV DNA and HBsAg levels according to their HBeAg status.

PMID- 25973161
TI  - Understanding autism in the light of sex/gender.

PMID- 25973162
TI  - The female protective effect in autism spectrum disorder is not mediated by a
      single genetic locus.
AB  - BACKGROUND: A 4:1 male to female sex bias has consistently been observed in
      autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a
      female protective effect (FPE) may account for part of this bias; however, the
      mechanism of such protection is unknown. Quantitative assessment of ASD symptoms
      using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique
      to females in multiplex families. This leads to the hypothesis that a single,
      common genetic locus on chromosome X might mediate the FPE and produce the ASD
      sex bias. Such a locus would represent a major therapeutic target and is likely
      to have been missed by conventional genome-wide association study (GWAS)
      analysis. METHODS: To explore this possibility, we performed an association study
      in affected versus unaffected females, considering three tiers of single
      nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that
      escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. RESULTS: No
      evidence of a SNP meeting the criteria for a single FPE locus was observed,
      despite the analysis being well powered to detect this effect. CONCLUSIONS: The
      results do not support the hypothesis that the FPE is mediated by a single
      genetic locus; however, this does not exclude the possibility of multiple genetic
      loci playing a role in the FPE.

PMID- 25973163
TI  - Sex differences in the corpus callosum in preschool-aged children with autism
      spectrum disorder.
AB  - BACKGROUND: Abnormalities in the corpus callosum have been reported in
      individuals with autism spectrum disorder (ASD), but few studies have evaluated
      young children. Sex differences in callosal organization and diffusion
      characteristics have also not been evaluated fully in ASD. METHODS: Structural
      and diffusion-weighted images were acquired in 139 preschool-aged children with
      ASD (112 males/27 females) and 82 typically developing (TD) controls (53 males/29
      females). Longitudinal scanning at two additional annual time points was carried
      out in a subset of these participants. Callosal organization was evaluated using
      two approaches: 1) diffusion tensor imaging (DTI) tractography to define
      subregions based on cortical projection zones and 2) as a comparison to previous
      studies, midsagittal area analysis using Witelson subdivisions. Diffusion
      measures of callosal fibers were also evaluated. RESULTS: Analyses of cortical
      projection zone subregions revealed sex differences in the patterns of altered
      callosal organization. Relative to their sex-specific TD counterparts, both males
      and females with ASD had smaller regions dedicated to fibers projecting to
      superior frontal cortex, but patterns differed in callosal subregions projecting
      to other parts of frontal cortex. While males with ASD had a smaller callosal
      region dedicated to the orbitofrontal cortex, females with ASD had a smaller
      callosal region dedicated to the anterior frontal cortex. There were also sex
      differences in diffusion properties of callosal fibers. While no alterations were
      observed in males with ASD relative to TD males, mean diffusivity (MD), axial
      diffusivity (AD), and radial diffusivity (RD) were all increased in females with
      ASD relative to TD females. Analyses of Witelson subdivisions revealed a decrease
      in midsagittal area of the corpus callosum in both males and females with ASD but
      no regional differences in specific subdivisions. Longitudinal analyses revealed
      no diagnostic or sex differences in the growth rate or change in diffusion
      measures of the corpus callosum from 3 to 5 years of age. CONCLUSIONS: There are
      sex differences in the pattern of altered corpus callosum neuroanatomy in
      preschool-aged children with ASD.

PMID- 25973164
TI  - Recurrence rates provide evidence for sex-differential, familial genetic
      liability for autism spectrum disorders in multiplex families and twins.
AB  - BACKGROUND: Autism spectrum disorders (ASDs) are more prevalent in males,
      suggesting a multiple threshold liability model in which females are, on average,
      protected by sex-differential mechanisms. Under this model, autistic females are
      predicted to carry a more penetrant risk variant load than males and to share
      this greater genetic liability with their siblings. However, reported ASD
      recurrence rates have not demonstrated significantly increased risk to siblings
      of affected girls. Here, we characterize recurrence patterns in multiplex
      families from the Autism Genetics Resource Exchange (AGRE) to determine if risk
      in these families follows a female protective model. METHODS: We assess
      recurrence rates and quantitative traits in full siblings from 1,120 multiplex
      nuclear families and concordance rates in 305 twin pairs from AGRE. We consider
      the first two affected children per family, and one randomly selected autistic
      twin per pair, as probands. We then compare recurrence rates and phenotypes
      between males and females and between twin pairs or families with at least one
      female proband (female-containing (FC)) versus those with only male probands
      (male-only (MO)). RESULTS: Among children born after two probands, we observe
      significantly higher recurrence in males (47.5%) than in females (21.1%; relative
      risk, RR = 2.25; adjusted P = 6.22e-08) and in siblings of female (44.3%) versus
      siblings of male probands (30.4%; RR = 1.46; adj. P = 0.036). This sex
      differential recurrence is also robust in dizygotic twin pairs (males = 61.5%,
      females = 19.1%; RR = 3.23; adj. P = 7.66e-09). Additionally, we find a
      significant negative relationship between interbirth interval and ASD recurrence
      that is driven by children in MO families. CONCLUSIONS: By classifying families
      as MO or FC using two probands instead of one, we observe significant recurrence
      rate differences between families harboring sex-differential familial liability.
      However, a significant sex difference in risk to children within FC families
      suggests that female protective mechanisms are still operative in families
      carrying high genetic risk loads. Furthermore, the male-specific relationship
      between shorter interbirth intervals and increased ASD risk is consistent with a
      potentially greater contribution from environmental factors in males versus
      higher genetic risk in affected females and their families. Understanding the
      mechanisms driving these sex-differential risk profiles will be useful for
      treatment development and prevention.

PMID- 25973165
TI  - Implementation of linked data in the life sciences at BioHackathon 2011.
AB  - BACKGROUND: Linked Data has gained some attention recently in the life sciences
      as an effective way to provide and share data. As a part of the Semantic Web,
      data are linked so that a person or machine can explore the web of data. Resource
      Description Framework (RDF) is the standard means of implementing Linked Data. In
      the process of generating RDF data, not only are data simply linked to one
      another, the links themselves are characterized by ontologies, thereby allowing
      the types of links to be distinguished. Although there is a high labor cost to
      define an ontology for data providers, the merit lies in the higher level of
      interoperability with data analysis and visualization software. This increase in
      interoperability facilitates the multi-faceted retrieval of data, and the
      appropriate data can be quickly extracted and visualized. Such retrieval is
      usually performed using the SPARQL (SPARQL Protocol and RDF Query Language) query
      language, which is used to query RDF data stores. For the database provider, such
      interoperability will surely lead to an increase in the number of users. RESULTS:
      This manuscript describes the experiences and discussions shared among
      participants of the week-long BioHackathon 2011 who went through the development
      of RDF representations of their own data and developed specific RDF and SPARQL
      use cases. Advice regarding considerations to take when developing RDF
      representations of their data are provided for bioinformaticians considering
      making data available and interoperable. CONCLUSIONS: Participants of the
      BioHackathon 2011 were able to produce RDF representations of their data and gain
      a better understanding of the requirements for producing such data in a period of
      just five days. We summarize the work accomplished with the hope that it will be
      useful for researchers involved in developing laboratory databases or data
      analysis, and those who are considering such technologies as RDF and Linked Data.

PMID- 25973166
TI  - Semantic enrichment of longitudinal clinical study data using the CDISC standards
      and the semantic statistics vocabularies.
AB  - BACKGROUND: There is an increasing recognition of the need for the data capture
      phase of clinical studies to be improved and for more effective sharing of
      clinical data. The Health Care and Life Sciences community has embraced semantic
      technologies to facilitate the integration of health data from electronic health
      records, clinical studies and pharmaceutical research. This paper explores the
      integration of clinical study data exchange standards and semantic statistic
      vocabularies to deliver clinical data as linked data in a format that is easier
      to enrich with links to complementary data sources and consume by a broad user
      base. METHODS: We propose a Linked Clinical Data Cube (LCDC), which combines the
      strength of the RDF Data Cube and DDI-RDF vocabulary to enrich clinical data
      based on the CDISC standards. The CDISC standards provide the mechanisms for the
      data to be standardised, made more accessible and accountable whereas the RDF
      Data Cube and DDI-RDF vocabularies provide novel approaches to managing large
      volumes of heterogeneous linked data resources. RESULTS: We validate our approach
      using a large-scale longitudinal clinical study into neurodegenerative diseases.
      This dataset, comprising more than 1600 variables clustered in 25 different sub
      domains, has been fully converted into RDF forming one main data cube and one
      specialised cube for each sub-domain. One sub-domain, the Medications specialised
      cube, has been linked to relevant external vocabularies, such as the Australian
      Medicines Terminology and the ATC DDD taxonomy and DrugBank terminology. This
      provides new dimensions on which to query the data that promote the exploration
      of drug-drug and drug-disease interactions. CONCLUSIONS: This implementation
      highlights the effectiveness of the association of the semantic statistics
      vocabularies for the publication of large heterogeneous data sets as linked data
      and the integration of the semantic statistics vocabularies with the CDISC
      standards. In particular, it demonstrates the potential of the two vocabularies
      in overcoming the monolithic nature of the underlying model and improving the
      navigation and querying of the data from multiple angles to support richer data
      analysis of clinical study data. The forecasted benefits are more efficient use
      of clinicians' time and the potential to facilitate cross-study analysis.

PMID- 25973167
TI  - Developing VISO: Vaccine Information Statement Ontology for patient education.
AB  - OBJECTIVE: To construct a comprehensive vaccine information ontology that can
      support personal health information applications using patient-consumer lexicon,
      and lead to outcomes that can improve patient education. METHODS: The authors
      composed the Vaccine Information Statement Ontology (VISO) using the web ontology
      language (OWL). We started with 6 Vaccine Information Statement (VIS) documents
      collected from the Centers for Disease Control and Prevention (CDC) website.
      Important and relevant selections from the documents were recorded, and knowledge
      triples were derived. Based on the collection of knowledge triples, the meta
      level formalization of the vaccine information domain was developed. Relevant
      instances and their relationships were created to represent vaccine domain
      knowledge. RESULTS: The initial iteration of the VISO was realized, based on the
      6 Vaccine Information Statements and coded into OWL2 with Protege. The ontology
      consisted of 132 concepts (classes and subclasses) with 33 types of relationships
      between the concepts. The total number of instances from classes totaled at 460,
      along with 429 knowledge triples in total. Semiotic-based metric scoring was
      applied to evaluate quality of the ontology.

PMID- 25973168
TI  - Evolution of eumalacostracan development-new insights into loss and reacquisition
      of larval stages revealed by heterochrony analysis.
AB  - BACKGROUND: Within Malacostraca (Crustacea), direct development and development
      through diverse forms of larvae are found. Recent investigations suggest that
      larva-related developmental features have undergone heterochronic evolution in
      Malacostraca. In the light of current phylogenetic hypotheses, the free-swimming
      nauplius larva was lost in the lineage leading to Malacostraca and evolved
      convergently in the malacostracan groups Dendrobranchiata and Euphausiacea. Here
      we reconstruct the evolutionary history of eumalacostracan (Malacostraca without
      Phyllocarida) development with regard to early appendage morphogenesis, muscle
      and central nervous system development, and determine the heterochronic
      transformations involved in changes of ontogenetic mode. RESULTS: Timing of 33
      developmental events from the different tissues was analyzed for six
      eumalacostracan species (material for Euphausiacea was not available) and one
      outgroup, using a modified version of Parsimov-based genetic inference (PGi). Our
      results confirm previous suggestions that the event sequence of nauplius larva
      development is partly retained in embryogenesis of those species which do not
      develop such a larva. The ontogenetic mode involving a nauplius larva was likely
      replaced by direct development in the malacostracan stem lineage. Secondary
      evolution of the nauplius larva of Dendrobranchiata from this ancestral
      condition, involved only a very small number of heterochronies, despite the
      drastic change of life history. In the lineage leading to Peracarida, timing
      patterns of nauplius-related development were lost. Throughout eumalacostracan
      evolution, events related to epidermal and neural tissue development were clearly
      less affected by heterochrony than events related to muscle development.
      CONCLUSIONS: Weak integration between mesodermal and ectodermal development may
      have allowed timing in muscle formation to be altered independently of ectodermal
      development. We conclude that heterochrony in muscle development played a crucial
      role in evolutionary loss and secondary evolution of a nauplius larva in
      Malacostraca.

PMID- 25973169
TI  - Key patterning genes contribute to leg elongation in water striders.
AB  - BACKGROUND: How adaptive phenotypes are shaped by the action of key developmental
      genes during ontogeny remains poorly understood. Water striders, a group of
      hemipteran insects, present a unique example of adaptation to life on the fluid
      water surface substrate. The group has undergone a set of leg modifications
      allowing them to efficiently move on the water surface and hence invade a variety
      of niches from ponds to open oceans. The elongated legs of water striders play a
      key role in generating efficient movement on the fluid by acting as propelling
      oars. RESULTS: To determine the developmental mechanisms underlying leg
      elongation, we examined the function of the key developmental genes
      decapentaplegic (dpp), wingless (wg), epidermal growth factor receptor (egfr),
      and hedgehog (hh) during embryonic development in the water strider Limnoporus
      dissortis. By analyzing expression patterns and RNAi knockdown phenotypes, we
      uncover the role of these genes in leg growth and patterning during
      embryogenesis. Our results indicate that wg and egfr contribute to the elongation
      of all the three segments of all thoracic legs, whereas hh specifies distal leg
      segments. CONCLUSIONS: Together, our results suggest that key patterning genes
      contribute to the dramatic elongation of thoracic appendages in water striders.

PMID- 25973170
TI  - Effect of advanced glycosylation end products on apoptosis in human adipose
      tissue-derived stem cells in vitro.
AB  - BACKGROUND: Both apoptosis and caspase-3 activity in adipose tissue-derived stem
      cells play an important role in the therapeutic process of diabetes patients. The
      purpose of this study was to investigate the effect of advanced glycation end
      products-human serum albumin (AGE-HSA) on apoptosis in human adipose tissue
      derived stem cells (ADSCs) and to characterize the signal transduction pathways
      activated by AGEs that are involved in apoptosis regulation. RESULTS: AGE-HSA
      promoted apoptosis and caspase-3 activity in ADSCs. However, the effects of AGE
      HSA were significantly attenuated by an inhibitor of p38 MAPK, but not by
      inhibitors of JNK MAPK or ERK MAPK. AGE-HSA also upregulated the expression of
      RAGE. Silencing of the RAGE gene inhibited AGE-HSA-induced apoptosis, and
      activation and expression of phosphorylated p38 MAPK. CONCLUSIONS: These results
      suggest that AGE-HSA promote the apoptosis of ADSCs in vitro via a RAGE-dependent
      p38 MAPK pathway.

PMID- 25973171
TI  - Tetrandrine is a potent cell autophagy agonist via activated intracellular
      reactive oxygen species.
AB  - BACKGROUND: Autophagy is an evolutionarily conserved cellular process that
      involves the lysosomal degradation of proteins and organelles and the recycling
      of cellular components to ensure cellular survival under external or internal
      stress. Numerous data has indicated that autophagy can be successfully targeted
      for the treatment of multiple cancers. We have previously demonstrated that
      tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the broadly used
      Chinese medicinal herb Stephaniae tetrandrae, exhibits potent antitumor effects
      when used either alone or in combination with other drugs. RESULTS: In the
      present study, we showed that tetrandrine is a broad-spectrum potent autophagy
      agonist. Although low-dose tetrandrine treatment does not affect cell viability,
      it can potently induce autophagy in a variety of cell lines, including cancerous
      cells and nontumorigenic cells. The autophagy inhibitors 3-methyladenine (3-MA)
      and chloroquine (CQ), effectively blocked tetrandrine-induced autophagy.
      Moreover, tetrandrine significantly triggered the induction of mitophagy. The
      underlying mechanisms are associated with the tetrandrine-induced production of
      intracellular reactive oxygen species (ROS), which plays a critical role in
      tetrandrine-induced autophagy. CONCLUSIONS: Here, we report that tetrandrine is a
      potent cell autophagy agonist and may have a wide range of applications in the
      fields of antitumor therapy and basic scientific research.

PMID- 25973172
TI  - Nanog down-regulates the Wnt signaling pathway via beta-catenin phosphorylation
      during epidermal stem cell proliferation and differentiation.
AB  - BACKGROUND: Skin tissue homeostasis is maintained by a balance between the
      proliferation and differentiation of epidermal stem cells (EpSCs). EpSC
      proliferation and differentiation are complex processes regulated by many factors
      and signaling pathways. This study aimed to explore the connection between the
      Nanog and the Wnt/beta-catenin pathway in the proliferation and differentiation
      of EpSCs. RESULTS: Our results demonstrated that during the study period, EpSC
      underwent differentiation when incubated in the presence neuropeptide substance P
      (SP), there was an opposing expression trend of Nanog and beta-catenin after SP
      treatment, which could be antagonized by the Wnt antagonist, Dkk-1. The
      transduced EpSCs had a greater proliferative ability than the SP treatment group
      and they did not undergo differentiation upon SP treatment. More important, beta
      catenin expression was down-regulated but phosphorylated beta-catenin expression
      and phosphorylated GSK-3beta expression was up-regulated upon Nanog
      overexpression. CONCLUSIONS: These results strongly suggest that Nanog plays an
      important role in maintaining the proliferation and differentiation homeostasis
      of EpSCs by promoting beta-catenin phosphorylation via GSK-3beta to inhibit the
      activity of the Wnt/beta-catenin signaling pathway. This is important for precise
      regulation of proliferation and differentiation of EpSC in the application of
      tissue engineering.

PMID- 25973173
TI  - Up-regulation of the Hippo pathway effector TAZ renders lung adenocarcinoma cells
      harboring EGFR-T790M mutation resistant to gefitinib.
AB  - BACKGROUND: The T790M mutation of epithelial growth factor receptor (EGFR) is a
      major cause of the acquired resistance to EGFR tyrosine kinase inhibitor (EGFR
      TKIs) treatment for lung cancer patients. The Hippo pathway effector, TAZ, has
      emerged as a key player in organ growth and tumorigenesis, including lung cancer.
      RESULTS: In this study, we have discovered high TAZ expression in non-small cell
      lung cancer (NSCLC) cells harboring dual mutation and TAZ depletion sensitized
      their response to EGFR-TKIs. Mechanistically, knockdown of TAZ in T790M-induced
      resistant cells leaded to reduced anchorage-independent growth in vitro, tumor
      formation and resistance to gefitinib in vivo, correlated with epithelial
      mesenchymal transition (EMT) and suppressed migration and invasion. Furthermore,
      we confirmed CTGF and AXL, novel EMT markers and potential therapeutic targets
      for overcoming EGFR inhibitor resistance, as directly transcriptional targets of
      TAZ. CONCLUSIONS: Taken together, this study suggests that expression of TAZ is
      an intrinsic mechanism of T790M-induced resistance in response to EGFR-TKIs.
      Combinational targeting on both EGFR and TAZ may enhance the efficacy of EGFR
      TKIs in acquired resistance of NSCLC.

PMID- 25973174
TI  - Unliganded TRs regulate growth and developmental timing during early
      embryogenesis: evidence for a dual function mechanism of TR action.
AB  - Recent genetic studies in the anuran Xenopus tropicalis reveal surprising new
      roles of thyroid hormone receptor in regulating growth and developmental timing
      in the absence of thyroid hormone. 

PMID- 25973175
TI  - Primary mental health prevention themes in published research and academic
      programs in Israel.
AB  - BACKGROUND: The World Health Organization Comprehensive Mental Health Action Plan
      (CMHAP) 2013-2020 proposes the implementation of primary prevention strategies to
      reduce the mental health burden of disease. The extent to which Israeli academic
      programs and published research adhere to the principles spelled out by the CMHAP
      is unknown. OBJECTIVE: To investigate the presence of mental health primary
      prevention themes in published research and academic programs in Israel. METHODS:
      We searched for mental health primary prevention themes in: (1) three major
      journals of psychiatry and social sciences during the years 2001-2012; (2)
      university graduate programs in psychology, social work and medicine in leading
      universities for the academic year of 2011-2012; and (3) doctoral and master's
      theses approved in psychology and social work departments in five universities
      between the years 2007-2012. We used a liberal definition of primary prevention
      to guide the above identification of themes, including those related to theory,
      methods or research information of direct or indirect application in practice.
      RESULTS: Of the 934 articles published in the three journals, 7.2%, n = 67,
      addressed primary prevention. Of the 899 courses in the 19 graduate programs
      5.2%, n = 47, elective courses addressed primary prevention. Of the 1960 approved
      doctoral and master's theses 6.2%, n = 123, addressed primary prevention. Only 11
      (4.7%) articles, 5 (0.6%) courses, and 5 (0.3%) doctoral and master's theses
      addressed primary prevention directly. CONCLUSIONS: The psychiatric reform
      currently implemented in Israel and WHO CMHAP call for novel policies and course
      of action in all levels of prevention, including primary prevention. Yet, the
      latter is rarely a component of mental health education and research activities.
      The baseline we drew could serve to evaluate future progress in the field.

PMID- 25973176
TI  - Health sector solidarity: a core European value but with broadly varying content.
AB  - Although the concept of solidarity sits at the center of many European health
      sector debates, the specific groups eligible for coverage, the financing
      arrangements, and the range of services and benefits that, together, compose the
      operational content of solidarity have all changed considerably over time. In
      prior economic periods, solidarity covered considerably fewer services or groups
      of the population than it does today. As economic and political circumstances
      changed, the content of solidarity changed with them. Recent examples of these
      shifts are illustrated through a discussion of health reforms in Netherlands,
      Germany and also Israel (although not in Europe, the Israeli health system is
      similar in structure to European social health insurance systems). This article
      suggests that changed economic circumstances in Europe since the onset of the
      2008 financial crisis may lead to re-configuring the scope and content of
      services covered by solidarity in many European health systems. A key issue for
      policymakers will be protecting vulnerable populations as this re-design occurs. 

PMID- 25580226
TI  - The ACCE method: an approach for obtaining quantitative or qualitative estimates
      of residual confounding that includes unmeasured confounding.
AB  - BACKGROUND:   Nonrandomized studies typically cannot account for confounding from
      unmeasured factors.  METHOD:   A method is presented that exploits the recently
      identified phenomenon of  "confounding amplification" to produce, in principle, a
      quantitative estimate of total residual confounding resulting from both measured
      and unmeasured factors.  Two nested propensity score models are constructed that
      differ only in the deliberate introduction of an additional variable(s) that
      substantially predicts treatment exposure.  Residual confounding is then
      estimated by dividing the change in treatment effect estimate between models by
      the degree of confounding amplification estimated to occur, adjusting for any
      association between the additional variable(s) and outcome. RESULTS:   Several
      hypothetical examples are provided to illustrate how the method produces a
      quantitative estimate of residual confounding if the method's requirements and
      assumptions are met.  Previously published data is used to illustrate that,
      whether or not the method routinely provides precise quantitative estimates of
      residual confounding, the method appears to produce a valuable qualitative
      estimate of the likely direction and general size of residual confounding.
      LIMITATIONS:   Uncertainties exist, including identifying the best approaches
      for: 1) predicting the amount of confounding amplification, 2) minimizing changes
      between the nested models unrelated to confounding amplification, 3) adjusting
      for the association of the introduced variable(s) with outcome, and 4) deriving
      confidence intervals for the method's estimates (although bootstrapping is one
      plausible approach). CONCLUSIONS:   To this author's knowledge, it has not been
      previously suggested that the phenomenon of confounding amplification, if such
      amplification is as predictable as suggested by a recent simulation, provides a
      logical basis for estimating total residual confounding. The method's basic
      approach is straightforward.  The method's routine usefulness, however, has not
      yet been established, nor has the method been fully validated. Rapid further
      investigation of this novel method is clearly indicated, given the potential
      value of its quantitative or qualitative output.

PMID- 25973178
TI  - Treatment of the later stages of Parkinson's disease - pharmacological approaches
      now and in the future.
AB  - The problems associated with the pharmacological treatment of the later stages of
      Parkinson's disease (PD) remain those seen over many years. These centre on a
      loss of drug effect ('wearing off') with disease progression, the occurrence of
      dyskinesia, notably with L-dopa use and the appearance of non-motor symptoms that
      are largely refractory to dopaminergic medication. Treatment strategies in late
      PD have been dominated by the use of drug combinations and the subtle
      manipulation of drug dosage. However, change is occurring as the understanding of
      the basis of motor complications and fluctuations and non-motor symptoms
      improves. New pharmacological options are expanding with the advent of longer
      acting versions of existing dopaminergic drugs, new drug delivery systems and the
      introduction of non-dopaminergic agents able to manipulate motor function both
      within the basal ganglia and in other brain regions. Non-dopaminergic agents are
      also being investigated for the treatment of dyskinesia and for the relief of non
      motor symptoms. However, while therapy continues to improve, the treatment of
      late stage PD remains problematic with non-motor symptoms dominating the unmet
      need in this patient group. 

PMID- 25973180
TI  - Prescribing Errors in UK Hospitals: Problems and Solutions.

PMID- 25973179
TI  - How to optimize the treatment of early stage Parkinson's disease.
AB  - The approach to early Parkinson's disease denotes the communication of the
      diagnosis and important decisions, such as when and how to start treatment.
      Evidence based medicine and guidelines indicate which drugs have robust evidence
      of efficacy and tolerability in this specific population. However, de-novo
      patients may show different characteristics and they may be in a different phase
      of their disease. In this review, we will give an insight into the appropriate
      time therapy should be started and the actual knowledge about disease
      modification therapies. Moreover, the drugs indicated for early treatment will be
      considered and an indication for the use of these drugs will be given with the
      support of the actual knowledge. 

PMID- 25973181
TI  - Commentary on "estimation of newborn risk for child or adolescent obesity:
      lessons from longitudinal birth cohorts".
AB  - Childhood obesity is an increasingly prevalent problem, associated with obesity
      later in life, and a sequalae of health problems such as metabolic syndrome and
      an increased risk of coronary heart disease. Poor nutrition and a lack of
      physical activity are said to be causes of obesity development, with genetic
      factors and heritability also implicated. However, there are established,
      identifiable risk factors associated with the future development of obesity, both
      in childhood, and adolescence. These include parental weight before pregnancy,
      gestational weight gain, pre-pregnancy maternal smoking, as well as numerous
      socioeconomic factors.(1-4) Studies have also shown that once obese, children can
      find it very difficult to lose the excess weight,(5) with long-term management
      methods having shown poor efficacy.(5) Therefore, preventative strategies are
      becoming a high priority to battle the ever-increasing epidemic of childhood
      obesity. This study by Morandi et al.(6) is the first longitudinal study to
      analyse the predictive properties of early life risk factors for obesity, and
      propose a subsequent predictive algorithm to identify newborns most at risk of
      becoming obese in childhood and adolescence. Morandi et al.'s study aimed to
      develop a clinically useful formula, which could be used to identify the risk of
      future obesity in newborns, thereby enabling more efficient implementation of
      prevention strategies.(6) The lifetime Northern Finland Birth Cohort 1986 (NFBC
      1986) was used to form predictive equations for both childhood and adolescent
      obesity, based on established risk factors: parental BMI, birth weight, maternal
      gestational weight gain, and socioeconomic factors. A genetic score was also
      created based on 39 BMI/obesity-associated polymorphisms. Validation studies were
      performed on both a retrospective cohort of children from Veneto, Italy, and a
      prospective cohort of children from Massachusetts, USA. 

PMID- 25973182
TI  - Commentary on "In Amenable Mortality - Deaths Avoidable Through Health Care -
      Progress in the US Lags That of Three European Countries".
AB  - Health care systems are often compared to evaluate and improve the delivery of
      healthcare to patients. The concept of 'amenable mortality' has been introduced
      as an indicator of quality of care.(1) Amenable mortality is defined as deaths
      from a collection of diseases, such as diabetes and appendicitis, that are
      potentially preventable given effective and timely health care.(1) This serves as
      a marker that highlights the performance of a health care system, although it has
      its limitations. A study by Nolte et al. found that the United States was slower
      to progress in improving amenable mortality when compared to United Kingdom,
      Germany, and France.(1) Table 1 showed that amenable mortality declined in all
      countries, although there was significant variation.(1) Further, the authors
      compared those under 65 to those over 65 years old between the countries. Those
      in the US under 65 had larger amenable mortality compared to other countries.
      Whilst Those over 65 in all the countries declined in amenable mortality, the US
      had a slower improvement rate.(1) In 2007 the US spent $7,290 US per capita on
      health care, more than twice the amount of France, Germany, and United Kingdom
      ($3,601; $3,588; $2,992 respectively) and yet the improvement in amenable
      mortality is half as good in certain populations compared to other Western
      countries.(2) The commonality amongst the three European countries is that they
      provided universal health care, while the US did not have this option. This
      appears to be further evidence for the need for health care reform in the US.(1).

PMID- 25973183
TI  - Commentary on "duration of resuscitation efforts and survival after in-hospital
      cardiac arrest: an observational study".
AB  - Decisions about the appropriate termination of resuscitation attempts are among
      the most important that teams must face, yet there have been very few studies
      looking into the issue. Many national guidelines refer only to advance decisions
      to prevent the initiation of resuscitation, such as DNAR orders,(1-3) and yet the
      decision to continue or abort on-going treatment is a clinical one, which should
      be evidence based like any other. This observational study(4) is one of the
      largest to examine the relationship between length of resuscitation efforts in
      hospital and outcome, and provides novel, powerful, and highly relevant results.
      The authors tested the hypothesis that hospitals with longer attempted duration
      of resuscitation in patients who don't survive would correlate with higher
      hospital survival outcomes, both immediate and to discharge. They assessed
      whether higher survival rates were associated with poor neurological status;
      additionally they directly estimated risk ratios for various at-risk groups,
      including breakdowns by cardiac rhythm. Hospital data was collected from 'Get
      With The Guidelines - Resuscitation'; the largest world-wide in-hospital
      resuscitation registry, managed by the American Heart Association.(5) Between
      2000-2008, 64,339 cardiac arrests were considered that lasted at least 2 minutes
      (to exclude 'partial arrests') in 435 hospitals in the USA, each with a minimum
      experience of at least 10 arrests over 8 years. Exclusions were made for
      Emergency Departments, operating theatres, postoperative areas, procedure areas,
      rehabilitation areas, and arrests with area unknown, to avoid the 'distinct
      circumstances' of arrests in those settings. The median value for each hospital
      was calculated, and hospitals were divided into quartiles based on median length
      of resuscitation in non-survivors, with corresponding lengths of 16, 19, 22, and
      25 minutes. Median resuscitation times overall were 17 minutes (IQR 10-26), with
      a breakdown of 12 minutes (IQR 6-21) for immediate survivors and 20 minutes (IQR
      14-30) for non-survivors.(4). 

PMID- 25973185
TI  - Screening for and management of obesity in adults: u.s. Preventive services task
      force recommendation statement: a policy review.

PMID- 25973184
TI  - Is Health Care a Right? Health Reforms in the USA and their Impact Upon the
      Concept of Care.
AB  - In 2008 United States President Barack Obama declared that health care "should be
      a right for every American".(1) This statement, although noble, does not reflect
      US healthcare statistics in recent times, with the number of uninsured reaching
      over 50 million in 2010.(2) Such disparity has sparked a political drive towards
      change, and the introduction of the Patient Protection and Affordable Care Act
      (PPACA).(3) These changes have been highly polemical, raising the fundamental
      question of whether health care is a right; a contract between the nation and its
      inhabitants granted at birth, or an entitlement; a privilege that must be earned
      as opposed to universally provided. Access to healthcare in the US is mediated by
      insurance coverage, either in the form of private or employer based cover, which
      may be government based for public sector employees or private for private sector
      employees. The majority of spending on healthcare however, comes from government
      expenditure on health programs such as Medicare, Medicaid, Tricare, and the State
      Children's Health Insurance Program (SCHIP).(4) Medicare is a federal government
      funded social insurance program that provides health insurance to people aged 65
      and older, younger people with disabilities, and those with end stage renal
      failure requiring dialysis. Medicaid is a means tested insurance coverage program
      for individuals with low incomes and their families, and is jointly funded by
      state and federal governments. Tricare is a healthcare program that provides
      healthcare insurance for military personnel, retirees, and their dependents. The
      SCHIP provides states with federal government funding to provide health insurance
      to children from families with modest incomes that do not qualify for Medicaid.
      As such, although the majority of the US population is insured by federal, state,
      employer, or private health insurance, the remainders go uninsured. 

PMID- 25973186
TI  - Test, learn, adapt.

PMID- 25973187
TI  - Maternal Choice in the UK Should Be Promoted Despite the Current Era of Financial
      Austerity.

PMID- 25973188
TI  - Lower limb peripheral arterial disease (clinical guideline 147): a guideline
      summary.

PMID- 25973189
TI  - In response: simulation-based trial of surgical-crisis checklists.

PMID- 25973190
TI  - Adenocarcinoma of the ileum: A rare and challenging entity.
AB  - INTRODUCTION: Primary small bowel malignancy is unusual and accounts for 1-3% of
      all gastrointestinal tract neoplasms. Adenocarcinoma is one of the most common
      histologic types, but its frequency decreases with more distal locations. Its
      clinical presentation is nonspecific and is usually associated with advanced
      disease, which contributes to delayed diagnosis. PRESENTATION OF CASE: A 66-year
      old woman was admitted to the hospital with a 6-day history of progressively
      worsening abdominal pain localized in the right lower quadrant, nausea, and
      vomiting. Investigation revealed an inflammatory appendiceal tumor. The patient
      underwent surgery and an unexpected tumor involving the distal ileal segment and
      ileocecal appendix was found. Right radical hemicolectomy with en bloc resection
      of the distal ileum was performed. Histopathological examination revealed
      adenocarcinoma of the ileum. DISCUSSION: This rare entity is associated with a
      nonspecific clinical presentation that contributes to delayed diagnosis and
      treatment, and consequently to a worse prognosis. Approximately half of the cases
      are only diagnosed at surgery. Primary treatment consists of wide resection with
      locoregional lymphadenectomy. The role of adjuvant chemotherapy has yet to be
      determined. CONCLUSION: This case demonstrates an unusual condition characterized
      by late and challenging diagnosis. We highlight the importance of an earlier
      diagnosis and optimal treatment for improved patient outcomes.

PMID- 25973191
TI  - Attitudes towards the surgical safety checklist and factors associated with its
      use: A global survey of frontline medical professionals.
AB  - BACKGROUND: The Surgical Safety Checklist (SSC) has been shown to reduce
      perioperative errors and complications and its implementation is recommended by
      the World Health Organisation (WHO). However, it is unknown how widely this
      intervention is used. We investigated attitudes and factors associated with use
      of WHO SSC in frontline medical professionals across the globe using a survey
      distributed through social networks. METHODS: A survey of usage and opinions
      regarding the SSC was posted on the Facebook and Twitter pages of a not-for
      profit surgical news website for one month (March 2013). Respondents were grouped
      into four groups based on their country's Gross National Income: high, upper
      middle, lower middle and low income. Univariate and multivariate analyses were
      performed to investigate how different factors were associated with the use of
      the SSC. RESULTS: 6269 medical professionals from 69 countries responded to the
      survey: most respondents were from lower middle (47.4%) countries, followed by:
      high (35.0%), upper middle (14.6%), and low (3.0%) income countries. In total,
      57.5% reported that they used the WHO SSC perioperatively. Fewer respondents used
      the WHO SSC in upper middle, lower middle and low income countries (LMICs)
      compared to high income countries (43.5% vs. 83.5%, p < 0.001). Female (61.3% vs.
      56.4% males, p = 0.001), consultant surgeons (59.6% vs. 53.2% interns, p < 0.001)
      and working in university hospitals (61.4% vs. 53.7% non-university hospitals, p
      < 0.001) were more likely to use the SSC. Believing the SSC was useful, did not
      work or caused delays was independently associated with the respondents reported
      use of the SSC (OR 1.22 95% CI 1.07-1.39; OR 0.47 95% CI 0.36-0.60; OR 0.64 95%
      CI 0.53-0.77, respectively). CONCLUSION: This study suggests the use of the WHO
      SSC is variable across countries, especially in LMICs where it has the most
      potential to improve patient safety. Critical appraisal of the documented
      benefits of the WHO SSC may improve its adoption by those not currently using it.

PMID- 25973192
TI  - Tall cell carcinoma arising in a thyroglossal duct cyst: A case report.
AB  - INTRODUCTION: Thyroglossal duct cyst carcinomas are extremely rare and their
      clinical presentation is similar to that of benign cysts. The diagnosis is based
      on physical examination, laboratory tests, and most importantly multiple imaging
      techniques (ultrasonography, computed tomography and magnetic resonance imaging),
      and fine needle aspiration cytology. PRESENTATION OF CASE: We report a very
      unusual case of a tall cell variant of papillary carcinoma arising in a
      thyroglossal duct cyst in association with a follicular variant of papillary
      microcarcinoma and a tall cell variant of papillary carcinoma arising from the
      thyroid gland. DISCUSSION: Although rarely described in the medical literature,
      ectopic thyroid tissue present in the thyroglossal duct cyst could be involved in
      the development of a poorly differentiated carcinoma. The frequent observation of
      an associated primitive thyroid carcinoma makes surgical management of thyroid
      gland controversial. CONCLUSION: For the optimal management of this rare
      pathological condition, a comprehensive preoperative evaluation and meticulous
      intra-operative appraisal are fundamental.

PMID- 25973193
TI  - Biological, psychological and social processes that explain celebrities'
      influence on patients' health-related behaviors.
AB  - BACKGROUND: Celebrities can have substantial influence as medical advisors.
      However, their impact on public health is equivocal: depending on the advice's
      validity and applicability, celebrity engagements can benefit or hinder efforts
      to educate patients on evidence-based practices and improve their health
      literacy. This meta-narrative analysis synthesizes multiple disciplinary insights
      explaining the influence celebrities have on people's health-related behaviors.
      METHODS: Systematic searches of electronic databases BusinessSource Complete,
      Communication & Mass Media Complete, Humanities Abstracts, ProQuest Political
      Science, PsycINFO, PubMed, and Sociology Abstracts were conducted. Retrieved
      articles were used to inform a conceptual analysis of the possible processes
      accounting for the substantial influence celebrities may have as medical
      advisors. RESULTS: Fourteen mechanisms of celebrity influence were identified.
      According to the economics literature, celebrities distinguish endorsed items
      from competitors and can catalyze herd behavior. Marketing studies tell us that
      celebrities' characteristics are transferred to endorsed products, and that the
      most successful celebrity advisors are those viewed as credible, a perception
      they can create with their success. Neuroscience research supports these
      explanations, finding that celebrity endorsements activate brain regions involved
      in making positive associations, building trust and encoding memories. The
      psychology literature tells us that celebrity advice conditions people to react
      positively toward it. People are also inclined to follow celebrities if the
      advice matches their self-conceptions or if not following it would generate
      cognitive dissonance. Sociology explains how celebrities' advice spreads through
      social networks, how their influence is a manifestation of people's desire to
      acquire celebrities' social capital, and how they affect the ways people acquire
      and interpret health information. CONCLUSION: There are clear and deeply rooted
      biological, psychological and social processes that explain how celebrities
      influence people's health behaviors. With a better understanding of this
      phenomenon, medical professionals can work to ensure that it is harnessed for
      good rather than abused for harm. Physicians can discuss with their patients the
      validity of celebrity advice and share more credible sources of health
      information. Public health practitioners can debunk celebrities offering
      unsubstantiated advice or receiving inappropriate financial compensation, and
      should collaborate with well-meaning celebrities, leveraging their influence to
      disseminate medical practices of demonstrated benefit.

PMID- 25973194
TI  - Understanding and defining bullying - adolescents' own views.
AB  - BACKGROUND: The negative consequences of peer-victimization on children and
      adolescents are major public health concerns which have been subjected to
      extensive research. Given all efforts made to analyze and estimate the social and
      health consequences of peer-victimization, the adolescents' own experiences and
      understandings have had surprisingly little impact on the definition of bullying.
      Therefore, the aim of the current study is to explore adolescents' definitions of
      bullying. METHODS: A questionnaire study (n = 128) and four focus group
      interviews (n = 21) were conducted among students aged 13 and 15. First, gender
      and age differences were analyzed with respect to what behaviors are considered
      bullying (questionnaire data). Second, analysis of what bullying is (focus group
      interviews) was conducted using qualitative content analysis. RESULTS: The
      adolescents own understanding and definition of bullying didn't just include the
      traditional criteria of repetition and power imbalance, but also a criterion
      based on the health consequences of bullying. The results showed that a single
      but hurtful or harmful incident also could be considered bullying irrespective of
      whether the traditional criteria were fulfilled or not. Further, girls and older
      students had a more inclusive view of bullying and reported more types of
      behaviors as bullying compared to boys and younger students. CONCLUSIONS: The
      results of the current study adds to the existing literature by showing that
      adolescents consider the victim's experience of hurt and harm as a criterion for
      defining bullying and not only as consequences of bullying. This may be of
      special relevance for the identification and classification of bullying incidents
      on the internet where devastating consequences have been reported from single
      incidents and the use of the traditional criteria of intent, repetition and power
      imbalance may not be as relevant as for traditional bullying. It implies that the
      traditional criteria included in most definitions of bullying may not fully
      reflect adolescents' understanding and definition of bullying. Assessments of
      bullying behaviors that ask adolescents to strictly adhere to the traditional
      definition of bullying might not identify all adolescents experiencing peer
      victimization and therefore not provide estimates of prevalence rates reflecting
      adolescents' own understanding of bullying.

PMID- 25973196
TI  - Modeling time-to-cure from severe acute malnutrition: application of various
      parametric frailty models.
AB  - BACKGROUND: In developing countries about 3.5% of children aged 0-5 years are
      victims of severe acute malnutrition (SAM). Once the morbidity has developed the
      cure process takes variable period depending on various factors. Knowledge of
      time-to-cure from SAM will enable health care providers to plan resources and
      monitor the progress of cases with SAM. The current analysis presents modeling
      time-to-cure from SAM starting from the day of diagnosis in Wolisso St. Luke
      Catholic hospital, southwest Ethiopia. METHODS: With the aim of coming up with
      appropriate survival (time-to-event) model that describes the SAM dataset,
      various parametric clustered time-to-event (frailty) models were compared.
      Frailty model, which is an extension of the proportional hazards Cox survival
      model, was used to analyze time-to-cure from SAM. Kebeles (villages) of the
      children were considered as the clustering variable in all the models. We used
      exponential, weibull and log-logistic as baseline hazard functions and the gamma
      as well as inverse Gaussian for the frailty distributions and then based on AIC
      criteria, all models were compared for their performance. RESULTS: The median
      time-to-cure from SAM cases was 14 days with the maximum of 63 days of which
      about 83% were cured. The log-logistic model with inverse Gaussian frailty has
      the minimum AIC value among the models compared. The clustering effect was
      significant in modeling time-to-cure from SAM. The results showed that age of a
      child and co-infection were the determinant prognostic factors for SAM, but sex
      of the child and the type of malnutrition were not significant. CONCLUSIONS: The
      log-logistic with inverse Gaussian frailty model described the SAM dataset better
      than other distributions used in this study. There is heterogeneity between the
      kebeles in the time-to-cure from SAM, indicating that one needs to account for
      this clustering variable using appropriate clustered time-to-event frailty
      models.

PMID- 25973195
TI  - Dietary intake and phthalates body burden in boys and girls.
AB  - BACKGROUND: Phthalates are a group of environmental endocrine disruptors and have
      been ubiquitously applied in industrial field. Few studies had investigated how
      dietary intake was related with phthalate body burden in children. To determine
      the relationship between phthalate body burden and dietary intake among school
      age children in Shanghai, China. METHODS: Four hundred and thirty schoolchildren
      aged 8-16 years were recruited in a cross-sectional study with 18 months follow
      up in Shanghai, China during 2010-2012. Data of questionnaire-based dietary
      intake were collected and urinary phthalate concentrations were measured.
      Associations between frequency of dietary intake and phthalate metabolite
      concentrations were evaluated by stepwise multiple linear regression model.
      RESULTS: Positive association was found between mono-butyl phthalate and seafood,
      and negative associations were found between mono-butyl phthalate and dried
      fruits and vegetables. Egg consumption showed negative association with all di-(2
      ethylhexyl) phthalate-related metabolites. CONCLUSIONS: Some food types were
      identified to be associated with phthalate body burden and diet might be a source
      of phthalate exposure among Chinese schoolchildren.

PMID- 25973197
TI  - Peripheral muscle strength and functional capacity in patients with moderate to
      severe asthma.
AB  - BACKGROUND: The adequate control of asthma includes the absence of nocturnal
      symptoms, minimal use of medication, normal or nearly normal lung function and no
      limitations to physical activity. The choice of a more sedentary lifestyle can
      lead to physical de-conditioning, thereby aggravating asthma symptoms and
      increasing the risk of obesity. METHODS: This study aimed at performing a battery
      of function-related assessments in patients with asthma and comparing them to a
      healthy control group. A prospective, transversal and case-control study was
      designed. It was set up at Santa Casa de Misericordia Hospital -Sao Paulo and
      Nove de Julho University on a population of outpatients. Subjects of the study
      were patients affected by moderate to severe asthma. A case-control study was
      carried out involving 20 patients with moderate to severe asthma and 15 healthy
      individuals (control group). All participants underwent body composition analysis
      (BMI and BIA) and a controlled walk test (Shuttle test), resistance muscle test
      (1RM) and answered a physical activity questionnaire (IPAQ). The group with
      asthma also answered a questionnaire addressing the clinical control of the
      illness (ACQ). RESULTS: In comparison to the control group (unpaired Student's t
      test), the patients with asthma had a significantly higher BMI (31.09 +/- 5.98
      vs. 26.68 +/- 7.56 kg/m(2)) and percentage of body fat (38.40 +/- 6.75 vs. 33.28
      +/- 8.23%) as well as significantly lower values regarding distance traveled on
      the walk test (369 +/- 110 vs. 494 +/- 85 meters) and metabolic equivalents (3.74
      +/- 0.87 vs. 4.72 +/- 0.60). A strong correlation was found between the distance
      completed and peripheral muscle strength (r: 0.57, p < 0.05) and METs (Metabolic
      equivalents - minutes/week) and peripheral muscle strength of 1RM (r: 0.61, p =
      0.009). CONCLUSIONS: The individuals with asthma had lower functional capacity
      and levels of physical activity as well as a higher percentage of body fat
      compared to healthy individuals. This suggests that such patients have a reduced
      physical performance stemming from a sedentary lifestyle. Despite the existence
      of few studies reporting moderate to severe asthmatic patients and functional
      capacity assessment, it is clear that the assessment presented in the current
      study is a valid and accessible tool in clinical practice.

PMID- 25973198
TI  - INDACO project: COPD and link between comorbidities, lung function and inhalation
      therapy.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by
      respiratory and extrarespiratory components referring both to systemic
      complications of COPD, like skeletal muscle myopathy, weight loss and others, and
      frequently associated comorbidities, interesting various organs and systems
      (cardiovascular diseases, malignancies, osteoporosis, diabetes, etc.). These
      comorbidities may increase the rate of hospitalization of COPD patients and have
      a huge effect on the outcomes of the respiratory disease. Inhalation therapy of
      COPD with bronchodilators and steroid is primary driven by airflow obstruction,
      symptoms like dyspnoea, and acute exacerbations. INDACO project has been
      developed in 2013 to assess the prevalence and type of comorbidities in COPD
      patients referred to the outpatient wards of some hospitals in Central and South
      Italy and a preliminary report has recently been published. In the present study,
      after widening that database, we evaluate the prevalence of comorbidities and the
      relationships between comorbidities and sex, age, symptoms, lung function and
      inhalation therapy in COPD patients. METHODS: In each enrolled patient,
      anthropometric and anamnestic data, smoking habits, respiratory function, GOLD
      (Global initiative for Chronic Obstructive Lung Disease) severity stage, Body
      Mass Index (BMI), number of acute COPD exacerbations in previous years, presence
      and type of comorbidities, and the Charlson Comorbidity Index (CCI) were
      recorded. RESULTS: We collected data of 569 patients (395 males and 174 females,
      mean age 73 +/- 8.5 yrs). The prevalence of patients with comorbidities was
      81.2%. Overall number of comorbidities was not related to airflow obstruction and
      age, but to acute exacerbation of COPD, dyspnoea measured with MRC scale, and
      male gender. A subgroup analysis revealed that ischaemic heart disease was
      predominant in males, whereas mood disorders in females. The use of a more
      complex (multi-drug) inhalation therapy was related with bronchial obstruction
      measured by FEV1/FVC (p for trend = 0.003) and number of comorbidities (p for
      trend = 0.001). In multivariate analysis, only airflow obstruction and number of
      comorbidities were determinant of complexity of therapy, but not MRC and acute
      exacerbation of COPD. However, the statistical model reached an extreme low
      degree of significance (r^2 = 0.07). CONCLUSIONS: Our study showed a high
      prevalence of comorbidities in COPD, with some differences related to gender.
      Number of comorbidities and airflow obstruction represent the determinant of
      inhalation therapy prescription. Dyspnoea and acute exacerbation of COPD,
      unlikely suggested by guidelines, are not significant drivers of therapy in the
      real life setting of our study.

PMID- 25973199
TI  - Urban schistosomiasis and associated determinant factors among school children in
      Bamako, Mali, West Africa.
AB  - BACKGROUND: Schistosomiasis is classically described as a rural disease that
      occurs in areas with poor sanitary conditions. However, over recent decades,
      there has been an expansion of schistosomiasis foci towards urban areas faced
      with a rapid and disordered urbanization. In Bamako, Mali, the impact of
      environmental change on vector-borne diseases such as schistosomiasis is not well
      known. This study sought to identify the presence of schistosomiasis transmission
      hotspots in Bamako. Using this perspective, we aimed to describe the risk factors
      of the endemization and maintenance of schistosomiasis. MATERIALS AND METHODS: A
      cross-sectional study was carried out in the six municipalities (communes) in
      Bamako. Environmental information was obtained from earth observation satellites
      in order to maximize ecological contrasts. Twenty-nine blocks of 200 m x 200 m
      were identified. We selected a school inside or nearest to each block for urine
      and stool samples examination. The study cohort was school children aged between
      eight and 15 years. The Kato-Katz technique and filtration were used for
      Schistosoma mansoni and S. haematobium ova research in stools and urine,
      respectively. The schools and snail breeding sites were georeferenced. Four
      malacological surveys were conducted between October 2011 and February 2012.
      Bivariate analysis was used to identify independent predictors of being infected
      with schistosomiasis. RESULTS: The prevalence rate of S. haematobium was 14.7% (n
      = 1,761) and that of S. mansoni 1.5% (n = 1,491). Overall, the urinary form was
      endemic in 76.6% of schools. The infection significantly varied between the
      municipalities (p < 0.001). It was also more prevalent on the left side of the
      Niger River than the right side (17.4% vs. 9.5% respectively; p < 0.001). The
      vicinity to snail breeding sites (OR = 3.677; 95% IC [2.765-4.889]; p < 10 (-3) )
      and parents' occupations (OR = 7.647; 95% IC [2.406-24.305]; p < 0.001) were the
      most important risk factors associated with S. haematobium infection exposure.
      Biomphalaria pfeifferi, Bulinus truncatus, and B. globosus were the intermediate
      hosts captured. The schistosome natural infection rates (SNIRs), which were low
      or nil in October and November, rose to 2.8% in January and 8.3% in February for
      B. pfeifferi and B. truncatus, respectively. CONCLUSION: Our findings show that
      there is a high transmission risk for schistosomiasis in Bamako. Appropriate
      integrated control measures need to be introduced to control the transmission of
      this disease in the study area.

PMID- 25973200
TI  - Ecohealth research in Southeast Asia: past, present and the way forward.
AB  - Ecohealth is a comprehensive approach to understanding health at its human,
      animal and environmental interface in a socio-ecological systems context. This
      approach was introduced widely in Southeast Asia (SEA) by the Canadian
      International Development Research Centre (IDRC) in the late 2000s. Aimed at
      addressing the problem of emerging infectious diseases (EIDs), numerous such
      projects and activities have been generated throughout the region. Ecohealth is
      increasingly converging with the One Health approach, as both movements emphasise
      a holistic understanding to health. We conducted a scoping review by considering
      all of the Ecohealth programmes, initiatives and projects that have been
      implemented in SEA since the introduction of the approach, and also gathered
      information from peer-reviewed literature. The objective of this paper is to
      review Ecohealth activities within SEA over the last 10 years to address the
      lessons learned, challenges faced and the way forward for Ecohealth in the
      region. Activities range from those focusing purely on capacity, projects
      focusing on research and projects covering both. Achievements to date include,
      for example, research contributing to the field of infectious diseases in
      relation to social ecological factors and associated urbanisation and
      agricultural intensification. Challenges remain at the project design and
      implementation level, in the available capacity and coordination to develop
      Ecohealth research teams in the countries, gauging teams' assimilation of
      Ecohealth's underlying tenets and their translation into sustainable disease
      prevention and control, as well as in the ability to scale up Ecohealth projects.
      We suggest that the way forward for Ecohealth should be from a regional
      perspective in terms of research, training and policy translation using Ecohealth
      in combination with the One Health approach. 

PMID- 25973201
TI  - An ecohealth assessment of poultry production clusters (PPCs) for the livelihood
      and biosecurity improvement of small poultry producers in Asia.
AB  - BACKGROUND: Poultry production cluster (PPC) programs are key strategies in many
      Asian countries to engage small commercial poultry producers in high-value
      production chains and to control infectious poultry diseases. This study assessed
      the multiple impacts of PPCs through a transdisciplinary ecohealth approach in
      four Asian countries, and drew the implications for small producers to improve
      their livelihoods and reduce the risk of spreading infectious diseases in the
      poultry sector. METHODS: The data collection combined both quantitative and
      qualitative methods. It comprised: formal structured household survey
      questionnaires, measuring the biosecurity level of poultry farms with a
      biosecurity score card; and key informant interviews. Descriptive statistics were
      used to process the quantitative data and a content analysis was used to process
      the qualitative data. RESULTS: This research found that poultry farms in clusters
      do not necessarily have better economic performance than those outside PPCs. Many
      farmers in PPCs only consider them to be an advantage for expanding the scale of
      their poultry operations and improving household incomes, and they are less
      concerned about-and have limited capacities to-enhancing biosecurity and
      environmental management. We measured the biosecurity level of farms in PPCs
      through a 14-item checklist and found that biosecurity is generally very low
      across all sample sites. The increased flies, mosquitoes, rats, and smells in and
      around PPCs not only pollute the environment, but also cause social conflicts
      with the surrounding communities. CONCLUSION: This research concluded that a
      poultry cluster, mainly driven by economic objectives, is not necessarily a
      superior model for the control of infectious diseases. The level of biosecurity
      in PPCs was found to be low. Given the intensity of poultry operations in PPCs
      (farms are densely packed into clusters), and the close proximity to residential
      areas of some PPCs, the risk of spreading infectious diseases, in fact,
      increases. Good management and collective action for implementing biosecurity
      measures are key for small producers in PPCs to address common challenges and
      pursue health-based animal production practices.

PMID- 25973202
TI  - Spatial cluster analysis of human cases of Crimean Congo hemorrhagic fever
      reported in Pakistan.
AB  - BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonotic
      disease that has been reported in almost all geographic regions in Pakistan. The
      aim of this study was to identify spatial clusters of human cases of CCHF
      reported in country. METHODS: Kulldorff's spatial scan statisitc, Anselin's Local
      Moran's I and Getis Ord Gi* tests were applied on data (i.e. number of laboratory
      confirmed cases reported from each district during year 2013). FINDINGS: The
      analyses revealed a large multi-district cluster of high CCHF incidence in the
      uplands of Balochistan province near it border with Afghanistan. The cluster
      comprised the following districts: Qilla Abdullah; Qilla Saifullah; Loralai,
      Quetta, Sibi, Chagai, and Mastung. Another cluster was detected in Punjab and
      included Rawalpindi district and a part of Islamabad. CONCLUSION: We provide
      empirical evidence of spatial clustering of human CCHF cases in the country. The
      districts in the clusters should be given priority in surveillance, control
      programs, and further research.

PMID- 25973204
TI  - Is there a single best estimator? Selection of home range estimators using area
      under-the-curve.
AB  - BACKGROUND: Global positioning system (GPS) technology for monitoring home range
      and movements of wildlife has resulted in prohibitively large sample sizes of
      locations for traditional estimators of home range. We used area-under-the-curve
      to explore the fit of 8 estimators of home range to data collected with both GPS
      and concurrent very high frequency (VHF) technology on a terrestrial mammal, the
      Florida panther Puma concolor coryi, to evaluate recently developed and
      traditional estimators. RESULTS: Area-under-the-curve was the highest for Florida
      panthers equipped with Global Positioning System (GPS) technology compared to VHF
      technology. For our study animal, estimators of home range that incorporated a
      temporal component to estimation performed better than traditional first- and
      second-generation estimators. CONCLUSIONS: Comparisons of fit of home range
      contours with locations collected would suggest that use of VHF technology is not
      as accurate as GPS technology to estimate size of home range for large mammals.
      Estimators of home range collected with GPS technology performed better than
      those estimated with VHF technology regardless of estimator used. Furthermore,
      estimators that incorporate a temporal component (third-generation estimators)
      appeared to be the most reliable regardless of whether kernel-based or Brownian
      bridge-based algorithms were used and in comparison to first- and second
      generation estimators. We defined third-generation estimators of home range as
      any estimator that incorporates time, space, animal-specific parameters, and
      habitat. Such estimators would include movement-based kernel density, Brownian
      bridge movement models, and dynamic Brownian bridge movement models among others
      that have yet to be evaluated.

PMID- 25973203
TI  - Cultural drivers and health-seeking behaviours that impact on the transmission of
      pig-associated zoonoses in Lao People's Democratic Republic.
AB  - Pig rearing is an important income source in the Lao People's Democratic Republic
      (PDR), with many smallholder farmers using traditional free-range pig production
      systems. Despite the potentially significant health risks posed by pig production
      regarding pig-associated zoonoses, information on the sociocultural drivers of
      these zoonoses is significantly lacking. This review summarises the existing
      sociocultural knowledge on eight pig-associated zoonoses suspected to be endemic
      in Southeast Asia: brucellosis, Q fever (Coxiella burnetii), trichinellosis,
      hepatitis E virus, leptospirosis, Japanese encephalitis, Streptococcus suis and
      Taenia solium taeniasis-cysticercosis. It summarises current knowledge on these
      diseases grouped according to their clinical manifestations in humans to
      highlight the propensity for underreporting. A literature search was conducted
      across multiple databases for publications from 1990 to the present day related
      to the eight pig-associated zoonoses and the risk and impact connected with them,
      with Lao PDR as a case study. Many of these pig-associated zoonoses have similar
      presentations and are often diagnosed as clinical syndromes. Misdiagnosis and
      underreporting are, therefore, substantial and emphasise the need for more robust
      diagnostics and appropriate surveillance systems. While some reports exist in
      other countries in the region, information is significantly lacking in Lao PDR
      with existing information coming mainly from the capital, Vientiane. The disease
      burden imposed by these zoonoses is not only characterised by morbidity and
      mortality, but directly impacts on livelihoods through income reduction and
      production losses, and indirectly through treatment costs and lost work
      opportunities. Other factors crucial to understanding and controlling these
      diseases are the influence of ethnicity and culture on food-consumption
      practices, pig rearing and slaughter practices, hygiene and sanitation, health
      seeking behaviours and, therefore, risk factors for disease transmission.
      Published information on the knowledge, attitudes and beliefs of people regarding
      pig zoonoses and their risk factors is also extremely limited in Lao PDR and the
      broader Southeast Asian region. The need for more transdisciplinary research,
      using a One Health approach, in order to understand the underlining social
      determinants of health and their impacts on health-seeking behaviours, disease
      transmission and, ultimately, disease reporting, cannot be more emphasized. 

PMID- 25973205
TI  - Do non-elite older runners slow down more than younger runners in a 100 km ultra
      marathon?
AB  - BACKGROUND: This study investigated changes in normalised running speed as a
      proxy for effort distribution over segments in male elite and age group 100 km
      ultra-marathoners with the assumption that older runners would slow down more
      than younger runners. METHODS: The annual ten fastest finishers (i.e. elite and
      age group runners) competing between 2000 and 2009 in the '100 km Lauf Biel' were
      identified. Normalised average running speed (i.e. relative to segment 1 of the
      race corrected for gradient) was analysed as a proxy for pacing in elite and age
      group finishers. For each year, the ratio of the running speed from the final to
      the first segment for each age cohort was determined. These ratios were combined
      across years with the assumption that there were no 'extreme' wind events etc.
      which may have impacted the final relative to the first segment across years. The
      ratios between the age cohorts were compared using one-way ANOVA and Tukey's post
      hoc test. The ratios between elite and age group runners were investigated using
      one-way ANOVA with Dunnett's multiple comparison post-hoc tests. The trend across
      age groups was investigated using simple regression analysis with age as the
      dependent variable. RESULTS: Normalised average running speed was different
      between age group 18-24 years and age groups 25-29, 30-34, 35-39, 40-44, 45-49,
      50-54, 55-59 and 65-69 years. Regression analysis showed no trend across age
      groups (r(2) = 0.003, p > 0.05). CONCLUSION: To summarize, (i) athletes in age
      group 18-24 years were slower than athletes in most other age groups and (ii)
      there was no trend of slowing down for older athletes.

PMID- 25973206
TI  - A description of the volume and intensity of sporadic physical activity among
      adults.
AB  - BACKGROUND: Emerging evidence indicates that accumulating physical activity in
      periods of less than 10 minutes, termed sporadic physical activity (SPA), has
      similar effects on health as a similar volume of bouted physical activity (BPA).
      The purpose of this study was to describe the volume and intensity of SPA in
      adults. METHODS: Participants consisted of a representative sample of 6040 adults
      aged 20 years and older from the 2003-2006 U.S. National Health and Examination
      Nutrition Survey. Physical activity was measured over 7 days using Actigraph AM
      7164 accelerometers. Each minute of accelerometer data was initially categorized
      by intensity (sedentary, light, moderate-to-vigorous), and then non-sedentary
      time was categorized as following a BPA or SPA pattern (>= or < 10 consecutive
      minutes). RESULTS: American adults accumulated 103 minutes/day of SPA of an
      intensity, which represented 27% of their total (BPA + SPA) daily physical
      activity. Only 3 minutes/day of the SPA was of a moderate-to-vigorous intensity;
      however, participants accumulated 16 minutes/day of moderate-to-vigorous activity
      embedded within light intensity BPA. This embedded moderate-to-vigorous activity
      represented 85% of total daily moderate-to-vigorous activity. CONCLUSIONS: SPA
      accounted for about a quarter of total daily physical activity. While the amount
      of moderate-to-vigorous SPA was minimal, a significant amount of moderate-to
      vigorous activity was accumulated within bouts of primarily light intensity
      activity.

PMID- 25973207
TI  - The feasibility and effectiveness of high-intensity boxing training versus
      moderate-intensity brisk walking in adults with abdominal obesity: a pilot study.
AB  - BACKGROUND: High-intensity interval training (HIIT) performed on exercise cycle
      or treadmill is considered safe and often more beneficial for fat loss and
      cardiometabolic health than moderate-intensity continuous training (MICT). The
      aim of this pilot study was to assess the feasibility and effectiveness of a 12
      week boxing training (HIIT) intervention compared with an equivalent dose of
      brisk walking (MICT) in obese adults. METHODS: Men and women with abdominal
      obesity and body mass index >25 kg/m(2) were randomized to either a boxing group
      or a brisk walking (control) group for 12 weeks. Each group engaged in 4 training
      sessions per week, equated for total physical activity. Feasibility outcomes
      included recruitment rates, assessment of training intensities, adherence and
      adverse events. Effectiveness was assessed pre and post intervention via
      pertinent obesity-, cardiovascular-, and health-related quality of life (HRQoL)
      outcomes. RESULTS: Nineteen individuals expressed an interest and 63% (n = 12)
      consented. Recruitment was slower than anticipated (1.3 participants/week). The
      boxing group trained at a significantly higher intensity each week versus the
      brisk walking group (p < 0.05). Two participants in the boxing group experienced
      an adverse event; both continued to exercise with modifications to the exercise
      program. No other adverse events were noted. The boxing group attended more
      sessions (79% vs. 55%) and had a lower attrition rate (n = 0 vs. n = 2) than the
      walking group. Analysis of covariance revealed that the boxing group
      significantly improved body fat percentage (p = 0.047), systolic blood pressure
      (p = 0.026), augmentation index (AIx; p < 0.001), absolute VO2max (p = 0.015),
      and Physical Functioning (p = 0.042) and Vitality (p = 0.024) domains of HRQoL
      over time. The walking group did not improve any clinical outcomes, and
      experienced a worsening of Vitality (p = 0.043). CONCLUSIONS: Boxing training
      (HIIT) in adults with abdominal obesity is feasible and may elicit a better
      therapeutic effect on obesity, cardiovascular, and HRQoL outcomes than an
      equivalent dose of brisk walking (MICT). Robustly designed randomized controlled
      trials are required to confirm these findings and inform clinical guidelines and
      practice for obesity treatment. TRIAL REGISTRATION:  TRIAL REGISTRATION:
      ACTRN12615000007538.

PMID- 25973208
TI  - Perceived personal importance of exercise and fears of re-injury: a longitudinal
      study of psychological factors related to activity after anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: Psychological perceptions are increasingly being recognized as
      important to recovery and rehabilitation post-surgery. This research
      longitudinally examined perceptions of the personal importance of exercise and
      fears of re-injury over a three-year period post anterior cruciate ligament (ACL)
      reconstruction. Stability and change in psychological perceptions was examined,
      as well as the association of perceptions with time spent in different types of
      physical activity, including walking, household activities, and lower and higher
      risk for knee injury activities. METHODS: Participants were athletes, 18-40 years
      old, who underwent ACL reconstruction for first-time ACL injuries. They were
      recruited from a tertiary care centre in Toronto, Canada. Participants completed
      interviewer-administered questionnaires pre-surgery and at years one, two and
      three, postoperatively. Questions assessed demographics, pain, functional
      limitations, perceived personal importance of exercise, fear of re-injury and
      physical activities (i.e., walking; household activities; lower risk for knee
      injury activities; higher risk for knee injury activities). Analyses included
      fixed-effect longitudinal modeling to examine the association of a fear of re
      injury and perceived personal importance of exercise and changes in these
      perceptions with the total hours spent in the different categories of physical
      activities, controlling for other factors. RESULTS: Baseline participants were 77
      men and 44 women (mean age = 27.6 years; SD = 6.2). At year three, 78.5% of
      participants remained in the study with complete data. Fears of re-injury
      decreased over time while personal importance of exercise remained relatively
      stable. Time spent in walking and household activities did not significantly
      change with ACL injury or surgery. Time spent in lower and higher risk of knee
      injury physical activity did not return to pre-injury levels at three years, post
      surgery. Greater time spent in higher risk of knee injury activities was
      predicted by decreases in fears of re-injury and by greater personal importance
      of exercise. CONCLUSIONS: This study highlights not only fears of re-injury,
      which has been documented in previous studies, but also the perceived personal
      importance of exercise in predicting activity levels following ACL reconstructive
      surgery. The findings can help in developing interventions to aid individuals
      make decisions about physical activities post knee injury and surgery.

PMID- 25973209
TI  - Relationship between perceived exertion and blood lactate concentrations during
      incremental running test in young females.
AB  - BACKGROUND: To investigate more practical handling of Borg's ratings of perceived
      exertion (RPE) and category-ratio scale of RPE (CR-10), we evaluated
      interrelationships between RPE, CR-10, and blood lactate concentrations (bLa)
      during incremental treadmill running tests for young females with different
      aerobic fitness levels. METHODS: Oxygen consumption, heart rate, bLa, RPE, and CR
      10 were measured from distance runners (DR; n = 15), race walkers (RW; n = 6),
      and untrained females (UT; n = 11). These variables corresponding to the lactate
      threshold (LT) and onset of blood lactate accumulation (OBLA) were compared among
      these groups. RESULTS: The UT had significantly lower RPE at LT than DR and RW,
      although the CR-10 at LT was not significantly different among these groups. The
      CR-10 at OBLA was significantly lower for the UT than DR. The relationship
      between bLa and CR-10 was approximated well by two linear regression lines in all
      groups. The bLa at the intersection only for the RW was significantly lower than
      that at LT, however, such intersections were observed at CR-10 = 3.1 to 3.2
      without significant group differences. The CR-10 scores at LT and intersections
      were not significantly different in each group. CONCLUSION: These results
      suggested that an intersection between CR-10 and bLa was observed at the CR-10
      score around three points of first half regardless of the aerobic fitness levels
      in young females, and such CR-10 scores would be associated with LT.

PMID- 25973210
TI  - Narrative review of primary care point-of-care testing (POCT) and antibacterial
      use in respiratory tract infection (RTI).
AB  - Antimicrobial resistance is a global problem and is being addressed through
      national strategies to improve diagnostics, develop new antimicrobials and
      promote antimicrobial stewardship. A narrative review of the literature was
      undertaken to ascertain the value of C reactive protein (CRP) and procalcitonin,
      measurements to guide antibacterial prescribing in adult patients presenting to
      GP practices with symptoms of respiratory tract infection (RTI). Studies that
      were included were randomised controlled trials, controlled before and after
      studies, cohort studies and economic evaluations. Many studies demonstrated that
      the use of CRP tests in patients presenting with RTI symptoms reduces antibiotic
      prescribing by 23.3% to 36.16%. Procalcitonin is not currently available as a
      point-of-care testing (POCT), but has shown value for patients with RTI admitted
      to hospital. GPs and patients report a good acceptability for a CRP POCT and
      economic evaluations show cost-effectiveness of CRP POCT over existing RTI
      management in primary care. POCTs increase diagnostic precision for GPs in the
      better management of patients with RTI. CRP POCT can better target antibacterial
      prescribing by GPs and contribute to national antimicrobial resistance
      strategies. Health services need to develop ways to ensure funding is transferred
      in order for POCT to be implemented. 

PMID- 25973211
TI  - Infective endocarditis in the Pacific: clinical characteristics, treatment and
      long-term outcomes.
AB  - INTRODUCTION: Data on clinical characteristics and outcomes of infective
      endocarditis (IE) in the Pacific are scarce. METHODS: Retrospective hospital
      based study in New Caledonia, a high-income country, on patients aged over 18
      years with definite IE according to the modified Duke criteria (2005-2010).
      RESULTS: 51 patients were included: 31 (60.8%) men; median age of 52.4 years (IQR
      33.0-70.0). Left-sided IE accounted for 47 (92.2%) patients: native valve IE in
      34 (66.7%) and prosthetic valve IE in 13 (25.5%). The main underlying heart
      disease included: rheumatic valve disease in 19 (37.3%), degenerative heart valve
      disease in 12 (23.5%) and congenital heart disease in 6 (11.8%). Significant
      comorbidities (Charlson's score >3) were observed in 20 (38.7%) patients.
      Infection was community acquired in 43 (84.3%) patients. Leading pathogens
      included Staphylococcus aureus in 16 (31.4%) and Streptococcus spp in 15 (29.4%)
      patients. Complications were noted in 33 patients (64.7%) and 24 (47.1%) were
      admitted to the intensive care unit. Cardiac surgery was eventually performed in
      22 of 40 (55.0%) patients with a theoretical indication. None underwent emergent
      cardiac surgery (ie, first 24 h); 2 (3.9%) were operated within 7 days; and 20
      (39.2%) beyond 7 days. 11 (21.6%) patients died in hospital and 21 (42.9%) were
      dead after a median follow-up of 28.8 months (IQR 4.6-51.2). Two (3.9%) were lost
      to follow-up. CONCLUSIONS: In New Caledonia, IE afflicts relatively young
      patients with rheumatic heart disease, and carries high complication and
      mortality rates. Access to heart surgery remains relatively limited in this
      remote archipelago.

PMID- 25973212
TI  - Impact of clinical follow-up and diagnostic testing on intervention for tetralogy
      of Fallot.
AB  - OBJECTIVE: Our purpose was to evaluate yield of tools commonly advocated for
      surveillance of tetralogy of Fallot (TOF). METHODS: All patients (pts) with TOF,
      seen at any time from 1/2008 to 9/2013 in an academic cardiology practice were
      studied. At the first and each subsequent outpatient visit, the use of tools
      including history and physical (H&P), ECG, Holter (HOL), echocardiogram (Echo),
      MR or CT (MR-CT) and stress testing (STR) were noted. Recommendations for
      intervention (INT) and for time to next follow-up were recorded; rationale for
      each INT with attribution to one or more tools was identified. RESULTS: There
      were 213 pts (mean 11.5 years, 130 male) who had 916 visits, 123 of which (13.4%)
      were associated with 138 INTs (47 surgical, 54 catheter-mediated, 37 other
      medical). Recommended follow-up interval was 9.44+/-6.5 months, actual mean
      follow-up interval was 11.7 months. All 916 (100%) patient visits had a H&P which
      contributed to 47.2% of INT decisions. Echo was performed in 652 (71.2%) of
      visits, and contributed to 53.7% of INTs. MR-CT was obtained in 129 (14.1%) of
      visits, and contributed to 30.1% of INTs. ECG was applied in 137 (15%) visits,
      and contributed to 1.6% of INTs. HOL was obtained in 188 (20.5%) visits, and
      contributed to 11.3% of INTs. STR was performed at 101 (11%) of visits, and
      contributed to 8.9% of INTs. CONCLUSIONS: INTs are common in repaired TOF, but
      when visits average every 11-12 months, most visits do not result in INT. H&P,
      Echo and HOL were the most frequently applied screens, and all frequently yielded
      relevant information to guide INT decisions. STR and MR/CT were applied as
      targeted testing and in this limited, non-screening role had high relevance for
      INT. There was low utilisation of ECG and major impact on INT was not
      demonstrated. Risk stratification in TOF may be possible, and could result in
      more efficient surveillance and targeted testing.

PMID- 25973213
TI  - Mechanical dyssynchrony is additive to ECG criteria and independently associated
      with reverse remodelling and clinical response to cardiac resynchronisation
      therapy in patients with advanced heart failure.
AB  - BACKGROUND: QRS duration and morphology are known established predictors of
      cardiac resynchronisation therapy (CRT) response, whereas mechanical dyssynchrony
      is not. Our aim was to determine if mechanical dyssynchrony provides independent
      prognostic information on CRT response. METHODS: We studied 369 consecutive
      patients with heart failure (HF) with low ejection fraction (EF) and widened QRS
      receiving CRT. Radial dyssynchrony (septal-posterior radial peak strain delay
      >=130 ms by speckle tracking) assessment was possible in 318 patients (86%).
      Associations with left ventricular end-systolic volume (LVESV) changes were
      examined using linear regression, and clinical outcomes analysed using Cox
      regression adjusted for multiple established outcome correlates. RESULTS:
      Patients with radial dyssynchrony before CRT (64%) had greater improvements in EF
      (8.8+/-9.4 vs 6.1+/-9.7 units, p=0.04) and LVESV (-30+/-41 vs -10+/-30 mL,
      p<0.01). Radial dyssynchrony was independently associated with reduction in LVESV
      (regression coefficient -10.5 mL, 95% CI -20.5 to -0.5, p=0.040) as was left
      bundle-branch block (-17.7 mL, -27.6 to -7.7, p=0.001). Patients with radial
      dyssynchrony had a 46% lower incidence of death, transplant or implantation of a
      left ventricular assist device (adjusted HR 0.54, 95% CI 0.31 to 0.92, p=0.02)
      and a 39% lower incidence of death or HF hospitalisation (0.61, 0.40 to 0.93,
      p=0.02) over 2 years. CONCLUSIONS: Radial dyssynchrony was associated with
      significant improvements in LVESV and clinical outcomes following CRT and is
      independent of QRS duration or morphology, and additive to current ECG selection
      criteria to predict response to CRT.

PMID- 25973214
TI  - Patients with overlap autoimmune disease differ from those with 'pure' disease.
AB  - OBJECTIVE: To determine frequency, demographic and treatment characteristics of
      patients with an overlapping second autoimmune illness (2nd AI). METHODS: We
      analysed two cohorts containing 897 patients with 'pure' systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome or
      antiphospholipid syndrome (APS) and 424 patients with one of these diagnoses plus
      at least one 2nd AI. RESULTS: A 2nd AI occurred in 38% of all patients diagnosed
      as having SLE (with or without a 2nd AI), 30% with RA, 52% with Sjogren's
      syndrome and 43% with APS. Compared to those without 2nd AI, patients with 2nd AI
      differ in age, sex, race and treatment at last visit. INTEPRETATION: These
      differences may have important implications for understanding treatments,
      outcomes and mechanisms of SLE and related diseases.

PMID- 25973215
TI  - The UK immunisation schedule: changes to vaccine policy and practice in 2013/14.
AB  - Vaccination programmes are implemented either as new vaccines become available or
      evidence about them accumulates, or in response to specific situations. In the
      United Kingdom, development and implementation of the national immunisation
      programme is centrally coordinated and funded by the Department of Health on
      behalf of England, Wales, Scotland and Northern Ireland. A number of significant
      changes were made to the UK immunisation schedule for 2013/2014. Three new
      vaccines were introduced: intranasal influenza and oral rotavirus for children
      and subcutaneous shingles for older adults. To ensure protection against
      meningococcal C infection into adulthood, there has been a change to the schedule
      for meningitis C vaccination. The temporary pertussis vaccination programme for
      pregnant women, set up in response to an increase in the number of cases of
      pertussis particularly among young babies, has been extended until further
      notice. Furthermore, in response to large outbreaks of measles in south Wales and
      other parts of the UK, a national measles, mumps and rubella catch-up campaign
      specifically targeted at unvaccinated children aged 10-16 years was launched to
      ensure that all children and young people have received two doses of measles,
      mumps and rubella vaccine. This review describes the rationale behind these
      policy changes. 

PMID- 25973216
TI  - Traumatic bifrontal extradural haematoma resulting from superior sagittal sinus
      injury: case report.
AB  - Traumatic bilateral extradural haematoma resulting from injury to the superior
      sagittal sinus is rare; in such cases, early surgical evacuation of the haematoma
      and control of bleeding from the sinus can achieve an excellent patient outcome. 

PMID- 25973217
TI  - Renal cell carcinoma presenting with malignant ascites.
AB  - It is rare for renal cell carcinoma to involve the peritoneum and cause malignant
      ascites. Furthermore, it is uncommon for malignant ascites to be a presenting
      feature of this cancer. An unusual case of renal cell carcinoma presenting with
      malignant ascites is reported, and its response to sunitinib described. 

PMID- 25973218
TI  - Cardiac magnetic resonance for the risk stratification of heart transplant
      recipients: ready for prime time?

PMID- 25973219
TI  - Amlodipine/valsartan single pill combination therapy in Chinese patients not
      controlled on previous monotherapy.

PMID- 25973220
TI  - Minimally invasive left ventricular assist device implantation: at the
      crossroads.

PMID- 25973221
TI  - How to analyze tumor stage data in clinical research.
AB  - Tumor staging serves as an important prognostic factor in cancer patient care. It
      also plays critical roles in cancer-related clinical research. Aimed to shed
      lights on how to analyze tumor staging related data and deliver proper
      interpretation, various statistical methods, from categorical data analysis to
      modeling techniques, were introduced through the examples. General guidelines
      were discussed for how to choose proper statistical test with key considerations
      of research aims, study design, measurement scale of data, proper data summary,
      type of associations, and underlying assumptions of statistical methods. 

PMID- 25973222
TI  - External validation of a prediction model for pathologic N2 among patients with a
      negative mediastinum by positron emission tomography.
AB  - BACKGROUND: A prediction model for pathologic N2 (pN2) among lung cancer patients
      with a negative mediastinum by positron emission tomography (PET) was recently
      internally validated. Our study sought to determine the external validity of that
      model. METHODS: A cohort study [2005-2013] was performed of lung cancer patients
      with a negative mediastinum by PET. Previously published model coefficients were
      used to estimate the probability of pN2 based on tumor location and size, nodal
      enlargement by computed tomography (CT), maximum standardized uptake value
      (SUVmax) of the primary tumor, N1 disease by PET, and pretreatment histology.
      RESULTS: Among 239 patients, 18 had pN2 [7.5%, 95% confidence interval (CI): 4.5
      12%]. Model discrimination was excellent (c-statistic 0.80, 95% CI: 0.75-0.85)
      and the model fit the data well (P=0.191). The accuracy of the model was as
      follows: sensitivity 100%, 95% CI: 81-100%; specificity 49%, 95% CI: 42-56%;
      positive predictive value (PPV) 14%, 95% CI: 8-21%, and negative predictive value
      (NPV) 100%, 95% CI: 97-100%. CI inspection revealed a significantly higher c
      statistic in this external validation cohort compared to the internal validation
      cohort. The model's apparently poor specificity for patient selection is in fact
      significantly better than usual care (i.e., aggressive but allowable guideline
      concordant staging) and minimum guideline mandated selection criteria for
      invasive staging. CONCLUSIONS: A prediction model for pN2 is externally valid.
      The high NPV of this model may allow pulmonologists and thoracic surgeons to more
      comfortably minimize the number of invasive procedures performed among patients
      with a negative mediastinum by PET.

PMID- 25973223
TI  - The link between mold sensitivity and asthma severity in a cohort of northern
      Chinese patients.
AB  - BACKGROUND: Mold sensitivity in asthmatic patients has recently attracted
      clinical interest; however the links between mold sensitivity and asthma severity
      in the Chinese population have been poorly characterized. In this study, we
      assess the relationship between asthma severity and airborne mold sensitivity in
      a cohort of northern Chinese patients. METHODS: Ninety-three non-smoking adult
      outpatients with asthma completed a questionnaire and underwent skin prick
      testing with five aeroallergens. For all patients, eosinophil cell counts, total
      serum IgE (sIgE) levels, and pulmonary function were measured. An asthma severity
      score was calculated based on the patient's forced expiratory volume in one
      second (FEV1), number of asthma attacks, number of hospital admissions, and use
      of inhaled or oral corticosteroids in the past year. RESULTS: Ninety-three
      patients were divided into three groups based on the results of their allergy
      tests: negative results for all tested allergens (group A, n=32); positive
      reactions to aeroallergens including mold antigens (group B, n=41); and positive
      reactions to aeroallergens other than molds (group C, n=20). Patients in group B
      had a lower FEV1 (74.46%+/-23.09% predicted) compared with group A (85.52%+/
      19.53%, P=0.023). Patients in both group B and C had elevated absolute eosinophil
      count (AEC) (group A: 3.12%+/-2.71%, group B: 5.41%+/-2.85%, group C: 6.1%+/
      4.49%; group A vs. group B, P=0.008; group A vs. group C, P=0.002), and total
      sIgE values (group A: 117.36+/-144.90 IU/mL, group B: 195.86+/-155.87 IU/mL,
      group C: 253.31+/-152.41 IU/mL; group A vs. group B, P=0.031; group A vs. group
      C, P=0.002) compared with patients in group A. Asthma severity scores were higher
      in patients in group B compared to patients in group C (7 vs. 5.5, P<0.05).
      Patients allergic to molds were more likely to have severe asthma [odds ratio
      3.636, 95% confidence interval (CI): 1.394 to 9.484; for severe versus mild
      asthma, P<0.05]. There was no association between asthma severity and
      sensitisation to house mites or weeds. CONCLUSIONS: Mold sensitivity is
      positively correlated with asthma severity in our cohort of northern Chinese
      patients.

PMID- 25973224
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for
      the identification of beta-hemolytic streptococci.
AB  - OBJECTIVE: Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) has emerged as promising technology for species
      identification. The purpose of this investigation was to compare the performance
      of MS and the traditional method for identification of beta-hemolytic
      streptococci (BHS). METHODS: Clinical BHS isolates were identified by the BD
      Phoenix SMIC/ID Streptococcal panels, and two MALDI-TOF MS platforms: the VITEK
      MS and the Bruker MALDI Biotyper systems respectively. In case of discordant
      results, 16sRNA sequencing was performed to provide the reference ID. RESULTS: A
      total of 96 isolates of BHS were analyzed. Thirty-six isolates (20.8%) were re
      tested by BD Phoenix for identification failure; and four isolates (4.2%) were
      rerun on the Bruker system for low identification score. No isolate need a second
      run for identification by Vitek MS system. Overall, BD Phoenix, BioTyper and
      Vitek MS automated system accurately identified 76 strains (79.2%), 91 (94.7%)
      strains and 92 (95.8%) strains, respectively. CONCLUSIONS: Our study suggests
      that MALDI-TOF MS is a superior method to conventional phenotypic methods for BHS
      identification.

PMID- 25973225
TI  - Endobronchial ultrasound with a guide sheath for small malignant pulmonary
      nodules: a retrospective comparison between central and peripheral locations.
AB  - OBJECTIVE: Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has
      improved the diagnostic accuracy of transbronchial biopsy (TBB) for malignant
      peripheral pulmonary nodules (PPNs). Many underscore the importance of tumor
      localization but reproducible results on other aspects that affect yield are few.
      We aimed to analyze the diagnostic performance of TBB with EBUS-GS and to know
      what group of patients can benefit most. METHODS: The database of patients with
      malignant PPNs (<=30 mm) who underwent EBUS-GS TBB at the National Cancer Center
      Hospital, Tokyo, Japan from April 2012 to March 2013 was retrospectively reviewed
      and analysed based on lesion and procedural characteristics. RESULTS: Most PPNs
      (N=212) were adenocarcinoma, measuring 20 mm [mean, standard deviation (SD)
      5.45]. Overall diagnostic accuracy was 67.5% (143 of 212 cases). Factors that
      significantly affected and predicted diagnostic success were EBUS probe within
      (P=0.001) and parenchymal location that was not adjacent to the costal visceral
      pleura (P=0.001). When combined, these variables achieved an 87% (59 of 68
      lesions) diagnostic yield. CT scan characteristic, lesion size, lobe location,
      and GS size were non-contributory. CONCLUSIONS: EBUS-GS TBB is an acceptable
      diagnostic method for small peripheral lung cancer. It can be maximized for PPNs
      that are away from the pleura and when the EBUS probe can be placed within the
      lesion.

PMID- 25973226
TI  - Systematic review and meta-analysis of the efficacy and safety of therapy with
      linezolid containing regimens in the treatment of multidrug-resistant and
      extensively drug-resistant tuberculosis.
AB  - BACKGROUND: Linezolid containing regimens have been proposed as potentially
      valuable alternatives for the treatment of patients with multidrug-resistant
      tuberculosis (MDR-TB) or extensively drug-resistant TB (XDR-TB). METHODS: A
      systematic review and meta-analysis was conducted to assess the efficacy, safety
      and tolerability of linezolid for drug-resistant TB (DR-TB) treatment. We
      searched the Cochrane Controlled Trial Registry, PubMed, Embase, Science Citation
      Index Expanded (SCI) and China National Knowledge Infrastructure (CNKI), database
      up to May 2014 to identify studies providing data of the use of linezolid for the
      treatment of DR-TB. RESULTS: The search yielded 15 studies (367 patients)
      including one randomized controlled trial (RCT), covering 239 patients who could
      be evaluated for effectiveness; 83% [95% confidence interval (CI), 75-90%;
      I(2)=62.8%] had a favorable outcome, defined as either cure or treatment
      completion. The pooled rate of culture conversion was 89% (95% CI, 83-95%;
      I(2)=49.6%). Between the group receiving daily linezolid doses of <=600 or >600
      mg, the mortality was considerably lower in patients treated with less than 600
      mg/day (P value <0.001). Of 367 patients for whom data on safety was available,
      peripheral neuropathy (31%, 95% CI, 19-42%; I(2)=81.7%) and anemia (25%, 95% CI,
      15-34%; I(2)=76.6%) were the main adverse effects. Patients receiving less than
      600 mg/day were more likely to experience nervous system adverse events (P value
      <0.01). CONCLUSIONS: The available evidence suggests that linezolid could be
      considered as a promising option as treatment of MDR/XDR TB. Randomized trials
      are warranted to define the dose and frequency of administration.

PMID- 25973227
TI  - Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar
      macrophages in a ventilator-induced lung injury model.
AB  - OBJECTIVE: To investigate the role of Toll-like receptor 2 (TLR2), TLR4, TLR9 and
      myeloid differentiation factor 88 (MyD88) on alveolar macrophages in ventilator
      induced lung injury (VILI). METHODS: Male, adult pathogen-free Sprague-Dawley
      rats weighing 300-350 g were used in this study. Animals were tracheotomized and
      allowed to breathe spontaneously for 4 h or mechanically ventilated for 4 h with
      low or high tidal volume (7 or 40 mL/kg). TLR2, TLR4, and TLR9, MyD-88 and NF
      kappaBeta of alveolar macrophages' expression under the different ventilation
      conditions were detected. Pulmonary permeability, lung inflammatory, IL-6 and IL
      1beta were assessed as well. RESULTS: Rats subjected to high tidal volume showed
      significantly greater pulmonary permeability and lung inflammatory than the
      control rats. Alveolar macrophages from rats subjected to high tidal volume also
      showed significantly higher protein expression of TLR2 (0.59+/-0.049 vs. 0.35+/
      0.036 and 0.36+/-0.031, both P<0.001), TLR4 (0.845+/-0.0395 vs. 0.401+/-0.026 and
      0.403+/-0.020, both P<0.001), TLR9 (0.727+/-0.074 vs. 0.383+/-0.039 and 0.367+/
      0.043, both P<0.001), MyD-88 (1.01+/-0.060 vs. 0.485+/-0.045 and 0.507+/-0.046,
      both P<0.001) and NF-kappaBeta (0.776+/-0.067 vs. 0.448+/-0.043 and 0.481+/
      0.047, both P<0.001), as well as significantly higher concentrations of IL-6
      (7.32+/-0.24 vs. 2.42+/-0.13 and 2.44+/-0.32, both P<0.001) and IL-1beta
      (139.95+/-9.37 vs. 53.63+/-5.26 and 53.55+/-6.63, both P<0.001) than the control
      and low tidal volume group. CONCLUSIONS: The overexpression of TLR2, TLR4, and
      TLR9 on alveolar macrophages and release of pro-inflammatory cytokines play a
      role in VILI.

PMID- 25973229
TI  - Efficacy of a simple and inexpensive exercise training program for advanced
      chronic obstructive pulmonary disease patients in community hospitals.
AB  - BACKGROUND: Exercise training is an important part of pulmonary rehabilitation;
      however it may not be appropriate for large-scale practice in community hospitals
      due to the complexity of the program and expensive training equipment, including
      cycle ergometry and treadmills. This study therefore aims to evaluate the
      efficacy of a more simplified exercise training program with inexpensive training
      equipment. METHODS: A multicentre study of a mild to moderate intensity exercise
      training program was conducted based on incremental strength and endurance with
      two 35-40-minute sessions per week for 8 weeks. The program was performed by 30
      outpatients from five community hospitals. Patients were monitored regularly for
      various parameters including strength of trained muscles, level of dyspnea, 6
      minute walk distance, and quality of life (QoL) at baseline at 1, 2, 3, 6, 9 and
      12 months. Unpaired t-tests were applied to determine the progress of trained
      muscle strength and minimal clinically important differences (MCIDs) were used to
      assess clinical outcomes. RESULTS: Thirty patients (13 males, 17 females) were
      enrolled with a mean age of 69.1+/-8.9 years, body mass index 20.5+/-4.4 kg/m(2),
      and mean % of predicted forced expiratory volume in the first second (FEV1)
      45.1+/-10.8. According to GOLD classification, eight (26.7%) cases were in stage
      II, 20 (66.7%) cases in stage III, and two (6.6%) cases in stage IV. Limb and
      chest wall muscle strength, dyspnea level, exercise capacity and QoL showed
      statistically significant improvements throughout the 12-month follow-up
      (P<0.01). There were clinically significant improvements in QoL throughout the 12
      month follow-up, exercise capacity from months 2 to 12, and dyspnea levels at
      months 2, 3 and 9. CONCLUSIONS: The implementation of a simplified and
      inexpensive exercise training program was shown to be effective for advanced
      chronic obstructive pulmonary disease patients in community hospitals.

PMID- 25973228
TI  - Effect of airway Pseudomonas aeruginosa isolation and infection on steady-state
      bronchiectasis in Guangzhou, China.
AB  - BACKGROUND: Current status of Pseudomonas aeruginosa (PA) infection in clinically
      stable bronchiectasis in mainland China remains unclear. OBJECTIVE: To compare
      the inflammation and lung function impairment in bronchiectasis patients isolated
      or infected with PA, potentially pathogenic microorganisms (PPMs) and commensals,
      and to identify factors associated with PA isolation and infection. METHODS:
      Patients with steady-state bronchiectasis and healthy subjects were recruited.
      Peripheral blood and sputum were sampled to determine inflammatory markers and
      bacterial loads in steady-state bronchiectasis and health. Spirometry and
      diffusing capacity were also measured. RESULTS: We enrolled 144 bronchiectasis
      patients and 23 healthy subjects. PA isolation and infection accounted for 44 and
      39 patients, who demonstrated significant inflammatory responses and markedly
      impaired spirometry, but not diffusing capacity, compared with healthy subjects
      and patients isolated with other PPMs and commensals (all P<0.05). Except for
      heightened sputum inflammatory responses, there were no notable differences in
      serum inflammation and lung function as with the increased density of PA. Female
      gender [odds ratio (OR): 3.10 for PA isolation; OR: 3.74 for PA infection], 4 or
      more exacerbations within 2 years (OR: 3.74 for PA isolation, OR: 2.95 for PA
      infection) and cystic bronchiectasis (OR: 3.63 for PA isolation, OR: 4.47 for PA
      infection) were the factors consistently associated with PA isolation and
      infection. CONCLUSIONS: PA elicits intense inflammation and lung function
      impairment in steady-state bronchiectasis. The density of PA does not correlate
      with most clinical indices. PA infection is associated with females, frequent
      exacerbations and cystic bronchiectasis.

PMID- 25973230
TI  - Addition to inhaled corticosteroids of leukotriene receptor antagonists versus
      theophylline for symptomatic asthma: a meta-analysis.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are widely used in combination with
      second controller medications in the management of asthma in adults and children.
      There lacks a systematic comparison between addition of leukotriene receptor
      antagonists (LTRAs) and theophylline to ICS. The purpose of this meta-analysis
      was to evaluate the difference of the efficacy and safety profile of adding
      either LTRAs or theophylline to ICS in adults and children with symptomatic
      asthma. METHODS: Randomised controlled trials (RCTs) published prior to November
      2014 were acquired through systematically searching and selected based on the
      established inclusion criteria for publications. The data extracted from the
      included studies were further analyzed by a meta-analysis. RESULTS: We included
      eight RCTs, of which six recruited adults and two recruited children aged 5 to 14
      years. The primary outcomes were changes in lung function from baseline,
      including forced expiratory volume in the first second (FEV1) and peak expiratory
      flow (PEF). Overall, addition of LTRAs led to significantly better morning PEF
      {mean difference (MD) 16.94 [95% confidence interval (CI): 11.49-22.39] L/min,
      P<0.01} and FEV1 [MD 0.09 (95% CI: 0.03-0.15) L, P=0.005] as compared to addition
      of theophylline. There were no differences between the two treatments in terms of
      evening PEF, adverse events, rescue medication use and asthma exacerbation.
      CONCLUSIONS: The combination of LTRA and ICS leads to modestly greater
      improvement in lung function than the combination of theophylline and ICS in the
      treatment of symptomatic asthma. Long-term trials are required to assess the
      efficacy and safety of these two therapies.

PMID- 25973231
TI  - A new simplified volume-loaded heterotopic rabbit heart transplant model with
      improved techniques and a standard operating procedure.
AB  - BACKGROUND: The classic non-working (NW) heterotopic heart transplant (HTX) model
      in rodents had been widely used for researches related to immunology, graft
      rejection, evaluation of immunosuppressive therapies and organ preservation. But
      unloaded models are considered not suitable for some researches. Accordingly, We
      have constructed a volume-loaded (VL) model by a new and simple technique.
      METHODS: Thirty male New Zealand White rabbits were randomly divided into two
      groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as
      donors and recipients. We created a large and nonrestrictive shunt to provide
      left heart a sufficient preload. The donor superior vena cave and ascending aorta
      (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena
      cava (IVC), respectively. RESULTS: No animals suffered from paralysis, pneumonia
      and lethal bleeding. Recipients' mortality and morbidity were 6.7% (1/15) and
      13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer
      than that in group NW. The maximal aortic velocity (MAV) of donor heart was
      approximately equivalent to half that of native heart in group VL. Moreover, the
      similar result was achieved in the parameter of late diastolic mitral inflow
      velocity between donor heart and native heart in group VL. The echocardiography
      (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during
      diastole and outflow during systole. PET-CT imaging showed the standard uptake
      value (SUV) of allograft was equal to that of native heart in both groups on the
      postoperative day 3. CONCLUSIONS: We have developed a new VL model in rabbits,
      which imitates a native heart hemodynamically while only requiring a minor
      additional procedure. Surgical technique is simple compared with currently used
      HTX models. We also developed a standard operating procedure that significantly
      improved graft and recipient survival rate. This study may be useful for
      investigations in transplantation in which a working model is required.

PMID- 25973232
TI  - A novel association of adenosine deaminase with paroxysmal atrial fibrillation: a
      propensity score analysis from a case-control study.
AB  - BACKGROUND: Prior work has identified age, body mass index, underlying heart
      disease, and other comorbidities as risk factors for atrial fibrillation. To
      date, studies have examined single baseline measures of traditional risk factors,
      and data on biomarker associations are lacking. OBJECTIVE: We sought to explore
      novel biochemical measures possibly associated with incident PAF after balancing
      the traditional risk factors. METHODS: Men or women aged >=18 years that were
      hospitalized between 1(st) Jan. 2010 and 31(st) Dec. 2013 for paroxysmal atrial
      fibrillation (PAF) and for health checkup (non-PAF) were included. We used
      propensity score methods to mitigate the influence of the nonrandom selection of
      PAF and non-PAF patients. Logistic regression was applied for analysis of risk
      factors for PAF. RESULTS: A total of 1,802 eligible patients were identified, in
      whom, 895 patients had at least one exclusion criterion. After excluding these
      patients, the total analytic cohort numbered 907 patients. Of these, 779 patients
      were for control group and 128 patients were for PAF group. Propensity score
      matching was used to obtain a balanced cohort of 124 patients per group. The PAF
      and non-PAF groups were well matched on demographic and clinical characteristics
      after propensity matching. Risk factors for PAF on multivariate stepwise logistic
      regression model included adenosine deaminase (ADA) [odds ratio (OR) =0.9160,
      P=0.015, 95% confidence interval (CI): 0.8536-0.9829], mitral valvular
      regurgitation (OR =3.4611, P=0.001, 95% CI: 1.7000-7.0467) and left atrial
      diameter (OR =1.0913, P=0.001, 95% CI: 1.0387-1.1465). Only the ADA was a
      protective factor for the occurrence of PAF. CONCLUSIONS: The ADA seems to be
      associated with PAF. The current study provides new insights into the prevention
      and treatment of PAF.

PMID- 25973233
TI  - Elevated expression of USP9X correlates with poor prognosis in human non-small
      cell lung cancer.
AB  - BACKGROUND: The aim of this study was to investigate the expression of ubiquitin
      specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC)
      patients and to evaluate the relevance of USP9X expression to tumor prognosis.
      METHODS: Ninety-five patients who underwent surgical resection for clinical stage
      I-IIIA NSCLC between July 2008 and July 2011 were included in this study.
      Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC
      tissues and 32 adjacent normal lung parenchymal tissues from these patients. The
      Chi-squared test was used to compare the clinicopathological characteristics
      between different groups. Kaplan-Meier analysis and a Cox regression model were
      used to determine the independent prognostic factors. A P value <0.05 was
      considered to be significant. RESULTS: The expression of USP9X was found to be
      significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung
      parenchymal tissue (6.3%) (P<0.001). High USP9X expression was significantly
      associated with positive lymph node metastasis (P<0.001), clinical stage
      (P<0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC.
      Based on the multivariate analysis, the elevated expression of the USP9X protein
      was a significant predictor of poor prognosis for NSCLC patients (HR =2.244,
      P=0.028). CONCLUSIONS: The current study demonstrated that the expression of
      USP9X in NSCLC tissue was significantly higher than that in normal lung tissue
      and that this elevated expression level of USP9X was associated with poor
      prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic
      biomarker for NSCLC.

PMID- 25973234
TI  - Surgical specimen histology revealed inadequacy of conventional transbronchial
      needle aspiration sample in the diagnosis of adenosquamous lung carcinoma.
AB  - OBJECTIVE: We retrospectively reviewed the accuracy of conventional
      transbronchial needle aspiration (cTBNA) in the subtyping of lesions located in
      or around central airways by comparing the histological diagnosis based on TBNA
      and surgical specimens. MATERIALS AND METHODS: cTBNA was conducted in consecutive
      patients with lesions located in or around the central airways (trachea, left and
      right primary bronchi, hilar and mediastinal masses or lymph nodes) between
      October 2012 and May 2014 in Wuhan No. 1 Hospital. The aspirated specimens in all
      patients were performed cytological and/or histopathological examination. Of
      these patients, some were subjected to surgical resection and histopathological
      examination was performed by the Department of Pathology. In the patients with
      gross specimens, the final diagnosis was established based on histopathological
      results from these specimens. RESULTS: In 63 patients diagnosed with cTBNA for
      the lesions located in or around the central airways, 23 patients with a
      diagnosis of lung cancer or atypical hyperplasia underwent surgery. The final
      diagnosis based on histopathology of surgery specimen was lung cancer in 22
      patients [3 small cell lung cancer (SCLC), 9 squamous cell carcinoma (SCC), 5
      adenocarcinoma (ADC), 4 adenosquamous carcinoma (ADS) and 1 neuroendocrine
      carcinoma], and inflammatory pseudotumor in 1 patient. The overall diagnostic
      yield of cTBNA for lung cancer was 95.7% (22/23), but the accuracy for
      histological typing of lung cancer is only 63.6% (14/22), for adenosquamous lung
      carcinoma was only 25% (1/4). CONCLUSIONS: cTBNA is a safe and effective
      procedure that can be used for the diagnosis of central lung cancer. However, the
      accuracy of TBNA for the histological classification of lung cancer is relatively
      low, especially for adenosquamous lung carcinoma.

PMID- 25973235
TI  - Effects of transdermal tulobuterol on dyspnea and respiratory function during
      exercise in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Poor exercise tolerability is a major barrier to improving the
      quality of life of patients with chronic obstructive pulmonary disease (COPD).
      Although COPD is often treated with long-acting beta2 adrenergic agonists, few
      studies have examined their effects on exercise tolerability. METHODS: In this
      study, Japanese COPD patients were treated with 2 mg transdermal tulobuterol, a
      long-acting beta2 agonist, once daily for 4 weeks. Spirometry and exercise tests
      were conducted at baseline and at the end of treatment. The patients conducted
      constant load (30 W for 5 min) and incremental load (starting at 10 W and
      increasing by 10 W every 1 min for 5 min to a maximum load of 50 W) exercise
      tests on a cycle ergometer. RESULTS: Thirteen patients with stable COPD
      participated in this study (mean age +/- standard deviation (SD), 69.5+/-9.7
      years; smoking history 55.9+/-27.8 pack-years). Resting spirometric parameters
      were unchanged at the end of treatment. The maximum Borg scale for dyspnea and
      the Borg scale slope (BSS) decreased significantly from baseline to the end of
      treatment. The threshold load of dyspnea (TLD) increased slightly, although not
      significantly, in the constant load test but not in the incremental load test.
      There were no changes in respiratory parameters during exercise after treatment.
      CONCLUSIONS: In conclusion, we found that treatment with transdermal tulobuterol
      for 4 weeks improved self-assessed dyspnea in Japanese COPD patients during
      constant and incremental exercise tests. This improvement in dyspnea may
      encourage patients to perform daily life activities or regular physical activity.

PMID- 25973236
TI  - Comparison of diagnostic performances among bronchoscopic sampling techniques in
      the diagnosis of peripheral pulmonary lesions.
AB  - BACKGROUND: There are many sampling techniques dedicated to radial endobronchial
      ultrasound (R-EBUS) guided flexible bronchoscopy (FB). However, data regarding
      the diagnostic performances among bronchoscopic sampling techniques is limited.
      This study was conducted to compare the diagnostic yields among bronchoscopic
      sampling techniques in the diagnosis of peripheral pulmonary lesions (PPLs).
      METHODS: A prospective study was conducted on 112 patients who were diagnosed
      with PPLs and underwent R-EBUS-guided FB between Oct 2012 and Sep 2014. Sampling
      techniques-including transbronchial biopsy (TBB), brushing cell block, brushing
      smear, rinsed fluid of brushing, and bronchoalveolar lavage (BAL)-were evaluated
      for the diagnosis. RESULTS: The mean diameter of the PPLs was 23.5+/-9.5 mm. The
      final diagnoses included 76 malignancies and 36 benign lesions. The overall
      diagnostic yield of R-EBUS-guided bronchoscopy was 80.4%; TBB gave the highest
      yield among the 112 specimens: 70.5%, 34.8%, 62.5%, 50.0% and 42.0% for TBB,
      brushing cell block, brushing smear, rinsed brushing fluid, and BAL fluid (BALF),
      respectively (P<0.001). TBB provided high diagnostic yield irrespective of the
      size and etiology of the PPLs. The combination of TBB and brushing smear achieved
      the maximum diagnostic yield. Of 31 infectious PPLs, BALF culture gave additional
      microbiological information in 20 cases. CONCLUSIONS: TBB provided the highest
      diagnostic yield; however, to achieve the highest diagnostic performance, TBB,
      brushing smear and BAL techniques should be performed together.

PMID- 25973237
TI  - Low-cost biportal endoscopic surgery for primary spontaneous pneumothorax.
AB  - BACKGROUND: Like many other countries, including the United States, China faces
      the problem of rising health care costs, which have become a heavy burden on the
      state and individuals. Endoscopic surgery offers many benefits. However, the need
      for more expensive endoscopic consumables brings further high medical costs.
      Therefore, the development of video-assisted thoracic surgery with no disposable
      consumables will help to control medical cost escalation. METHODS: Between
      October 2011 and September 2014, a series of 66 patients with primary spontaneous
      pneumothorax underwent hand ligation of blebs under biportal video-assisted
      thoracoscopic surgery or bullectomy with stapler during triportal video-assisted
      thoracoscopic surgery. After treatment of blebs, pleural abrasion was performed
      with an electrocautery cleaning pad. RESULTS: Compared with the group treated by
      bullectomy with stapler, we found a significant reduction in postoperative costs
      in the group with bleb ligation. There was no difference in operating time, chest
      tube drainage, and postoperative stay between the two groups. The follow-up
      period varied from 1 to 35 months and six cases of recurrence were noted.
      CONCLUSIONS: The technique that we described appears to offer better economic
      results than bullectomy with a stapler under three-port video-assisted
      thoracoscopic surgery for treating primary spontaneous. The clinical outcomes are
      similar.

PMID- 25973238
TI  - Higher expression of SIRT1 induced resistance of esophageal squamous cell
      carcinoma cells to cisplatin.
AB  - BACKGROUND: High expression of Sirtuin type 1 (SIRT1) exists in some cancer
      cells. However, it is still unclear whether SIRT1 affects the sensitivity of
      esophageal cancer cells to cisplatin. This study was designed to explore the
      relationship between SIRT1 expression and resistance of esophageal squamous cell
      carcinoma (ESCC) cells to cisplatin and reveal the underlying mechanism. METHODS:
      The tissue samples of 68 ESCC patients were collected from Nanjing Drum Tower
      Hospital, China. All the patients had undergone cisplatin based combination
      chemotherapy. The expression of SIRT1and Noxa in tissue samples were analyzed by
      quantitative real-time reverse PCR (qRT-PCR) and Western blot. Human ESCC cell
      line (ECa9706 cells) was cultured and a cisplatin-resistant subline (ECa9706-CisR
      cells) was established by continuous exposure to cisplatin at different
      concentrations. The expression of SIRT1 and Noxa in both cell lines was analyzed
      by qRT-PCR and Western blot. siRNA technology was utilized to down-regulate the
      SIRT1 expression in ECa9706-CisR cells. The influence of SIRT1 silence on
      sensitivity of ECa9706-CisR cells to cisplatin was confirmed using CCK-8 assay
      and flow cytometry. Furthermore, the level change of Noxa after SIRT1 silence in
      ECa9706-CisR cells was determined by qRT-PCR and Western blot. RESULT: SIRT1 and
      Noxa expression in chemo-resistant patients was significantly increased and
      decreased respectively, compared with chemo-sensitive patients. SIRT1 expression
      in ECa9706-CisR cells was significantly increased with a lower Noxa level,
      compared with normal ECa9706 cells. Cisplatin 5 uM could cause proliferation
      inhibition, G2/M phase arrest and apoptosis in ECa9706-CisR cells and these
      effects could be enhanced dramatically by SIRT1 silencing. Moreover, Noxa
      expression was increased after treated with SIRT1 siRNA. CONCLUSIONS: Over
      expression of SIRT1 may cause resistance of ESCC cells to cisplatin through the
      mechanism involved with Noxa expression.

PMID- 25973239
TI  - Study on risk factors and phenotypes of acute exacerbations of chronic
      obstructive pulmonary disease in Guangzhou, China-design and baseline
      characteristics.
AB  - BACKGROUND: To describe a study design that focuses on risk factors and patterns
      of chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: A 2-year,
      single centre, observational study was conducted in Guangzhou in China. The study
      enrolled 318 subjects with COPD aged 40-79 years, stratified into different but
      equally sized groups according to global initiative for chronic obstructive lung
      disease (GOLD) stage (including Stage 0) and 86 lung healthy controls. An
      assessment each year was scheduled including questionnaires, lung function
      testing, Chest X-ray and blood collection. A sub-group, called sub-group X,
      consisting of 203 subjects with COPD and 51 lung healthy controls, was selected
      to answer a symptom questionnaire daily (EXACT-PRO) via a BlackBerry Personal
      Digital Assistant (PDA) device. Upon an alert that indicated a change in daily
      symptom pattern, the patients were contacted by the clinic to decide whether they
      had experienced an exacerbation and should have an extra visit within 24-48
      hours. At an extra visit, nasal and throat swabs, induced sputum and blood were
      collected. Air pollution, temperature and humidity were also monitored daily. A
      subset of sub-group X, called sub-group M that consisted of 52 COPD patients and
      15 healthy controls was dedicated to measure muscle strength and a dexa scan.
      RESULTS: More than 78% of the enrolled patients completed the study successfully.
      There appeared a difference between the patient groups and the controls in
      gender, age, body mass index (BMI), forced expiratory volume in 1 second (FEV1),
      FEV1/FVC and smoking at baseline. In sub-group X 90 out of 203 (44.4%) selected
      COPD patients developed one or more exacerbations in the 2-year observation
      period. They were more severe COPD patients according to GOLD stage at study
      start. On average most exacerbations occurred in the month March and the least
      number of exacerbations occurred in October. CONCLUSIONS: This study with the
      obtained patient dataset will allow a better insight in many aspects of
      exacerbations in COPD (e.g., the identification, the risk factors, phenotypes and
      the biomarkers).

PMID- 25973240
TI  - How well does pathologic stage predict survival for esophageal adenocarcinoma
      after neoadjuvant therapy?
AB  - BACKGROUND: Cancer staging systems are designed to predict survival and stratify
      patients. The 7(th) edition of the American Joint Commission on Cancer (AJCC7)
      staging system for esophageal cancer was modeled using survival data on patients
      who underwent esophagectomy without induction or adjuvant therapy. In the United
      States, the standard of care for patients with locally advanced tumors often
      includes neoadjuvant therapy. The prognostic value of the pathologic stage for
      these patients is unknown. METHODS: Data from the Surveillance Epidemiology and
      End Results (SEER) were used to identify 1,243 patients with adenocarcinoma of
      the esophagus who underwent surgery after neoadjuvant therapy from 1988-2009.
      Included in the analysis were pathologically-staged, non-metastatic patients who
      had radiation as part of their neoadjuvant therapy. The AJCC7 staging system and
      an alternate system were modeled using Kaplan-Meier survival methods. The two
      systems were compared using log-rank chi-squared statistics, with large chi
      squared values indicating accuracy in survival prediction. RESULTS: The AJCC
      staging system was able to predict survival for patients who had neoadjuvant
      therapy (P<0.001, chi-squared =81.8); however, there was little distinction
      between stage subgroups. Patients with neoadjuvant radiotherapy had improved
      survival for pathologic stage II and III disease. An alternative, simpler staging
      system was better able to stratify patients with neoadjuvant therapy (P<0.001,
      chi-squared =100.5). CONCLUSIONS: The current AJCC staging system is able to
      predict survival in esophageal adenocarcinoma patients undergoing neoadjuvant
      therapy, however, there is less distinction among stage subgroups. An
      alternative, simpler stage grouping may better stratify patients receiving
      neoadjuvant therapy.

PMID- 25973241
TI  - Antimicrobial peptide LL-37 circulating levels in chronic obstructive pulmonary
      disease patients with high risk of frequent exacerbations.
AB  - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD)
      increase the decline in lung function, deterioration in health status and risk of
      death. The assessment of exacerbation risk is important in the grading of COPD.
      The most common cause of COPD exacerbation is respiratory tract infection. The
      only known human cathelicidin antimicrobial peptide, LL-37, play an important
      role in innate defense against infection. Its gene expression is regulated by the
      bioactive form of vitamin D. The objective of the present study was to explore
      the relationship between LL-37 plasma levels, vitamin D status and exacerbation
      risk in patients with COPD. METHODS: COPD patients and normal subjects were
      recruited from Beijing Hospital for this study. COPD patients were divided into
      low risk group and high risk group according to the criteria of GOLD strategy.
      The plasma concentrations of LL-37 were measured by ELISA technique to explore
      the difference in LL-37 levels between groups. The plasma levels of 25-hydroxy
      vitamin D [25(OH)D] were analyzed using electrochemiluminescence immunoassay
      (ECLIA). RESULTS: A total of 84 COPD patients and 51 normal subjects (control
      group) were recruited. COPD patients were divided into low risk group (37 cases)
      and high risk group (47 cases), depending on forced expiratory volume in one
      second (FEV1)%pred and exacerbation frequency in the previous year. The plasma
      concentrations of LL-37 in control group, low risk group and high risk group were
      20.7+/-5.8, 19.5+/-4.1 and 17.9+/-3.9 ug/L respectively. The plasma concentration
      of LL-37 was significantly lower in high risk group than in control group
      (P=0.006). But there was no significant difference between low risk group and
      high risk group (P=0.152). The plasma concentrations of 25(OH)D in control group,
      low risk group and high risk group were 18.1+/-9.4, 13.1+/-6.9 and 9.3+/-5.8
      ng/mL respectively. The plasma concentration of 25(OH)D was significantly higher
      in control group than in low risk group (P=0.004) or high risk group (P<0.001).
      The plasma concentration of 25(OH)D was significantly lower in high risk group
      than in low risk group (P=0.031). Hospitalization frequency for COPD
      exacerbations was negative correlated with plasma levels of LL-37 (r=-0.290,
      P=0.048) and 25(OH)D (r=-0.341, P=0.020) in high risk group. There was not
      significant correlation between LL-37 and 25(OH)D in COPD patients (r=0.115,
      P=0.303). CONCLUSIONS: The plasma levels of LL-37 and 25(OH)D were lower in COPD
      patients with high risk of frequent exacerbations than normal subjects. Low
      plasma levels of LL-37 and 25(OH)D might be predictors of exacerbation risk in
      COPD patients.

PMID- 25973242
TI  - Impact of daily bathing with chlorhexidine gluconate on ventilator associated
      pneumonia in intensive care units: a meta-analysis.
AB  - OBJECTIVE: Ventilator associated pneumonia (VAP) is the most important nosocomial
      infection in intensive care units (ICUs). Our objective was to assess whether
      daily bathing with chlorhexidine gluconate (CHG) would significantly result in
      the reduction of VAP. MATERIALS AND METHODS: Meta-analysis of randomized
      controlled trials (RCTs) and quasi-experimental studies were conducted. The
      setting are medical, surgical, trauma, and combined medical-surgical ICUs. The
      patients are adult. We searched electronic search engine (PubMed), Embase and the
      Cochrane Central Register database for all published studies related to the
      application of daily CHG bathing with VAP risk. RESULTS: In all, six articles
      reporting a total of 27,638 ventilator-days met the inclusion criteria; 132
      patients in the CHG arm developed a VAP (13,349 ventilator-days), compared with
      188 patients in the control arm (14,289 ventilator-days). Daily bathing with CHG
      was significantly associated with decreased incidence risk of VAP [relative risk
      (RR): 0.73, 95% confidence interval (CI): 0.57-0.92, I(2)=0%]. In the subgroup
      analysis, we found that daily bathing with 2% CHG impregnated cloths or wipes
      would reduce the incidence risk of VAP among before-and-after studies (pooled RR:
      0.73, 95% CI: 0.57-0.93). CONCLUSIONS: The application of daily bathing with CHG
      would decrease incidence risk of VAP, which would be an important complementary
      intervention to barrier precautions.

PMID- 25973243
TI  - Laparoscopic repair of Morgagni hernia by artificial pericardium patch in an
      adult obese patient.
AB  - BACKGROUND: Morgagni hernia is a kind of rare congenital diaphragmatic hernia. We
      reported a case of Morgagni hernia repaired successfully with artificial
      pericardium patch via the laparoscopic approach. METHODS: The patient was
      admitted with a 3-month history of postprandial nausea and vomiting, and
      accompanied by epigastric pain. Computed tomography (CT) scans showed a large
      anteromedial diaphragmatic hernia. The hernial contents were reduced back into
      the abdominal cavity and the diaphragmatic defect was repaired with artificial
      pericardium patch by laparoscopic intracorporeal suture. RESULTS: We achieved
      satisfactory intracorporeal repair of this large diaphragmatic defect. The
      patient had excellent recovery and started on oral diet on the first
      postoperative day, and then was discharged just two days after operation.
      CONCLUSIONS: The minimally invasive advantage of laparoscopic approach offers a
      secure, reliable and satisfactory way to confirm the diagnosis and achieve the
      repair of non-complicated Morgagni hernia.

PMID- 25973244
TI  - Conventional transbronchial needle aspiration with 23 gauge needle: a preliminary
      study.
AB  - BACKGROUND: Conventional transbronchial needle aspiration (cTBNA) is a safe and
      minimally invasive procedure with a high yield for the diagnosis of large lymph
      nodes (LNs) in favourable locations (LNs >1.5 cm in stations #4R and/or #7).
      However, it is usually underutilized by pulmonologist. One of the main reasons
      given for not performing cTBNA is the risk of puncturing vascular structures of
      the mediastinum. Recently, with the twofold objective of minimize the risk of
      bleeding and reduce the cTBNA cost, a thinner and less expensive needle has been
      commercialized. It is a 23 gauge (G) needle that costs 34, 37 ?. The aim of our
      study was to analyze the sample adequacy, diagnostic accuracy and safety of this
      needle in comparison with 21 and 22 G needles (average cost: 6,400 ?). METHODS:
      We retrospectively analysed medical records from patients who underwent
      bronchoscopy with cTBNA for the diagnosis of LNs >1.5 cm in stations #4R and/or
      #7 at the Thoracic Endoscopy Unit of the University Hospital of Parma from
      January 1st, 2007 to October 31(st), 2011. Five hundred patients underwent cTBNA
      from January 1(st), 2007 to October 31(st), 2011. In order to reduce the
      technical and personal bias for sampling procedure we analyzed only cases sampled
      by a single well-trained bronchoscopist, particularly skilful at cTBNA. RESULTS:
      A total of 222 patients (186 men; mean age 63 years+/-12, range 6-89) with LNs
      >1.5 cm in stations #4R and/or #7 were identified. A 23 G needle was used in 84
      patients (38%), a 21 G needle in 88 patients (40%) and a 22 G needle in 50
      patients (22%). No statistically significant differences between the 23 G group
      and the 21 or 22 G group in sample adequacy (P=0.78 and P=0.12, respectively) and
      diagnostic accuracy (P=0.9 and P=0.4, respectively) were found. There were no
      intraprocedural or postprocedural complications irrespective of the size of
      needle used. CONCLUSIONS: Transbronchial 23 G needle is as safe and effective as
      the 21 and 22 G needle for the sampling of LNs >1.5 cm in stations #4R and/or #7.
      For this reason, to obtain cytology specimens from large LNs in favourable
      locations, the 23 G needle may represent an alternative and less expensive choice
      compared to 21 and 22 G needles, even if our observation needs to be confirmed in
      a larger prospective study.

PMID- 25973245
TI  - Video-assisted thoracoscopic pneumonectomy.
AB  - BACKGROUND: Lung cancer often requires pneumonectomy. This procedure is
      challenging and usually performed by thoracotomy, which is traumatic and may
      involve complications. Video-assisted thoracoscopic surgery (VATS) lobectomy is a
      recognized procedure that has been accepted by surgeons. There is no standard
      procedure to perform a pneumonectomy using VATS. The aim of this paper is to
      share our experiences and to show our technique for performing a pneumonectomy
      using VATS. METHODS: A 65-year-old man was admitted to the First Affiliated
      Hospital of Chongqing Medical University. A thoracic computed tomography (CT)
      scan revealed a 56 mm * 45 mm * 40 mm lesion in the left upper lung lobe. Lesions
      involving the left lower lung lobe were also identified and the subcarinal and
      hilar lymph nodes were enlarged. A VATS pneumonectomy was performed. RESULTS: The
      total surgery time was approximately 90 min, the intraoperative blood loss was
      100 mL, the number of resected lymph nodes was 15; and the postoperative hospital
      stay was 8 days. Follow-up revealed no recurrence or metastasis for 6 months.
      CONCLUSIONS: Video-assisted thoracoscopic pneumonectomy is a safe and effective
      treatment procedure.

PMID- 25973247
TI  - Professor Jang-Ming Lee: how far will the robotic-assisted surgery go?

PMID- 25973246
TI  - Combined pulmonary fibrosis and emphysema (CPFE): an entity different from
      emphysema or pulmonary fibrosis alone.
AB  - Chronic obstructive pulmonary disease (COPD) and idiopathic interstitial
      pneumonias (IIP), with different radiological, pathological, functional and
      prognostic characteristics, have been regarded as separate entities for a long
      time. However, there is an increasing recognition of the coexistence of emphysema
      and pulmonary fibrosis in individuals. The association was first described as a
      syndrome by Cottin in 2005, named "combined pulmonary fibrosis and emphysema
      (CPFE)", which is characterized by exertional dyspnea, upper-lobe emphysema and
      lower-lobe fibrosis, preserved lung volume and severely diminished capacity of
      gas exchange. CPFE is frequently complicated by pulmonary hypertension, acute
      lung injury and lung cancer and prognosis of it is poor. Treatments for CPFE
      patients with severe pulmonary hypertension are less effective other than lung
      transplantation. However, CPFE has not yet attracted wide attention of clinicians
      and there is no research systematically contrasting the differences among CPFE,
      emphysema/COPD and IIP at the same time. The authors will review the existing
      knowledge of CPFE and compare them to either entity alone for the first time,
      with the purpose of improving the awareness of this syndrome and exploring novel
      effective therapeutic strategies in clinical practice. 

PMID- 25973248
TI  - Symptomatic malignant pericardial effusion due to advanced pericardial
      malignancies: a palliative approach.

PMID- 25973249
TI  - Extenuating symptoms is very important for malignant pericardial effusion.

PMID- 25973251
TI  - Erratum to "Dr. Paul Zarogoulidis: the exploration on pneumothorax and new use of
      EBUS".
AB  - [This corrects the article on p. S73 in vol. 7, PMID: 25774312.]. 

PMID- 25973252
TI  - The textbook on lung cancer: time for personalized medicine.

PMID- 25973253
TI  - The Statistical point of view of Quality: the Lean Six Sigma methodology.
AB  - Six Sigma and Lean are two quality improvement methodologies. The Lean Six Sigma
      methodology is applicable to repetitive procedures. Therefore, the use of this
      methodology in the health-care arena has focused mainly on areas of business
      operations, throughput, and case management and has focused on efficiency
      outcomes. After the revision of methodology, the paper presents a brief clinical
      example of the use of Lean Six Sigma as a quality improvement method in the
      reduction of the complications during and after lobectomies. Using Lean Six Sigma
      methodology, the multidisciplinary teams could identify multiple modifiable
      points across the surgical process. These process improvements could be applied
      to different surgical specialties and could result in a measurement, from
      statistical point of view, of the surgical quality. 

PMID- 25973254
TI  - Lies, damned lies, and marketing: an editor's lament.

PMID- 25973255
TI  - Chronic obstructive pulmonary disease patient group succeeds on the internet:
      EFFORTS.

PMID- 25973256
TI  - Gary Bain's precepts for chronic obstructive pulmonary disease patient groups.

PMID- 25973257
TI  - Intrathoracic desmoid tumor arising at a distance from thoracotomy sites after
      thoracoscopic segmentectomy: report of a case.
AB  - We report a case involving an intrathoracic desmoid tumor in a 68-year-old woman
      who had undergone video-assisted thoracoscopic right basal segmentectomy for lung
      cancer 1 year earlier. The well demarcated tumor was 9 cm * 6 cm * 6 cm in size,
      was located in the right apico-posterior thorax and had invaded the chest wall.
      The patient complained of a dull shoulder pain as a result of rapid tumor
      enlargement. En bloc tumor resection, including the apico-posterior chest wall
      extending from the 1st to the 4th rib, was successful. The patient had no
      recurrent tumor at 5 years after the second surgery. Intrathoracic desmoid tumor
      could occur, even when the tumor arises at a distance from the port and
      thoracotomy sites after thoracoscopic surgery. 

PMID- 25973258
TI  - Esophageal cancer revealing a tracheal diverticulum.
AB  - Tracheal diverticulum is a benign entity characterized by single or multiple
      invaginations of the tracheal wall, and is rarely encountered in clinical
      practice but frequently in postmortem examination as an incidental finding. Its
      combination with esophageal cancer is extremely rare. In this case report, we
      present a patient with these two lesions and analyze their correlation. 

PMID- 25973259
TI  - A large malignant thymomas of the anterior mediastinum.
AB  - The surgical treatment of large malignant thymomas of the anterior mediastinum is
      associated with a high risk. Recently, a patient with a large malignant thymoma
      of the anterior mediastinum was treated with surgery, and the outcome is
      satisfactory. The diagnosis of such tumors is mostly based on the chest X-ray and
      CT scans, as well as magnetic resonance imaging (MRI). Surgical treatment is the
      main effective treatment, and should be performed as soon as possible. 

PMID- 25973260
TI  - Benign esophago-pulmonary fistula complicating achalasia: case report and
      literature review.
AB  - The achalasia, a common benign disease of esophagus, plays an important role in
      esophago-respiratory fistula, which has not yet been well recognized. In present
      study, a case is reported of a patient with benign esophago-pulmonary fistula
      secondary to a longstanding achalasia. To our knowledge, this is the fifth
      patient of English literature presenting benign esophago-pulmonary fistula
      associated with achalasia, we performed Heller's myotomy as well as
      fundoplication through trans-abdominal route and colon replacement of the
      esophagus through retro-sternal procedure, but with the thoracic esophageal
      fistula as well as the right lung left being intact. The patient is going on well
      in the follow up. 

PMID- 25973261
TI  - Bronchial involvement in chronic eosinophilic pneumonia: a case report.
AB  - Chronic eosinophilic pneumonia (CEP) is an idiopathic chronic condition
      characterized by alveolar filling with mixed inflammatory infiltrate consisting
      largely of eosinophils. On CT, it is usually observed as consolidation, often
      peripheral and patchy in distribution, with upper lobe dominance. Airway
      involvement in CEP is very rare. We report on a case of bronchial involvement in
      CEP. 

PMID- 25973262
TI  - Two are Better Than One: Valuing Medical Friendship.

PMID- 25973264
TI  - International collaboration: promises and challenges.
AB  - We currently face a myriad of grand global challenges in fields such as poverty,
      the environment, education, science, and medicine. However, our current means of
      dealing with such challenges has fallen short, and ingenious solutions are
      required to overcome the inherent resistance to progress toward ameliorating such
      difficulties. Here, we highlight the promises and challenges of international
      collaboration in achieving success toward these trials. We note prior successes
      in fields such as education, medicine, science, and environmental issues made to
      date, yet at the same time we do note deficiencies and shortcomings in these
      efforts. Hence, the notion of international collaboration should be strengthened
      and encouraged by governments, non-profit organizations, and others moving
      forward using creative means to bring talented teams together to tackle these
      challenges across the globe. 

PMID- 25973263
TI  - Teaching and assessing professionalism in medical learners and practicing
      physicians.
AB  - Professionalism is a core competency of physicians. Clinical knowledge and skills
      (and their maintenance and improvement), good communication skills, and sound
      understanding of ethics constitute the foundation of professionalism. Rising from
      this foundation are behaviors and attributes of professionalism: accountability,
      altruism, excellence, and humanism, the capstone of which is professionalism.
      Patients, medical societies, and accrediting organizations expect physicians to
      be professional. Furthermore, professionalism is associated with better clinical
      outcomes. Hence, medical learners and practicing physicians should be taught and
      assessed for professionalism. A number of methods can be used to teach
      professionalism (e.g. didactic lectures, web-based modules, role modeling,
      reflection, interactive methods, etc.). Because of the nature of professionalism,
      no single tool for assessing it among medical learners and practicing physicians
      exists. Instead, multiple assessment tools must be used (e.g. multi-source
      feedback using 360-degree reviews, patient feedback, critical incident reports,
      etc.). Data should be gathered continuously throughout an individual's career.
      For the individual learner or practicing physician, data generated by these tools
      can be used to create a "professionalism portfolio," the totality of which
      represents a picture of the individual's professionalism. This portfolio in turn
      can be used for formative and summative feedback. Data from professionalism
      assessments can also be used for developing professionalism curricula and
      generating research hypotheses. Health care leaders should support teaching and
      assessing professionalism at all levels of learning and practice and promote
      learning environments and institutional cultures that are consistent with
      professionalism precepts. 

PMID- 25973265
TI  - When Suicide Is Not Suicide: Self-induced Morbidity and Mortality in the General
      Hospital.
AB  - Suicidal phenomena in the general hospital can take a variety of forms that can
      be parsed by taking into account whether or not the patient 1) intended to hasten
      death, and 2) included collaborators, including family and health care providers,
      in the decision to act. These two criteria can be used to distinguish entities as
      diverse as true suicide, non-compliance, euthanasia/physician-assisted suicide,
      and hospice/palliative care. Characterizing the nature of "suicide" events
      facilitates appropriate decision-making around management and disposition. 

PMID- 25973266
TI  - Clinical empathy and narrative competence: the relevance of reading talmudic
      legends as literary fiction.
AB  - The "curative potential" in almost any clinical setting depends on a caregiver
      establishing and maintaining an empathic connection with patients so as to
      achieve "narrative competence" in discerning and acting in accord with their
      preferences and best interests. The "narrative medicine" model of shared "close
      reading of literature and reflective writing" among clinicians as a means of
      fostering a capacity for clinical empathy has gained validation with recent
      empirical studies demonstrating the enhancement of theory of mind (ToM), broadly
      conceived as empathy, in readers of literary fiction. Talmudic legends, like that
      of Rabbi Judah's death, are under-appreciated, relevant sources of literary
      fiction for these efforts. The limitations of narrative medicine are readily
      counterbalanced by simultaneously practiced attention to traditional bioethical
      principles, including-especially-beneficence, non-maleficence, and autonomy. 

PMID- 25973267
TI  - A Chaplain-led Spiritual Life Review Pilot Study for Patients with Brain Cancers
      and Other Degenerative Neurologic Diseases.
AB  - OBJECTIVE: This pilot study was designed to describe changes in spiritual well
      being (SWB), spiritual coping, and quality of life (QOL) in patients with brain
      cancer or other neurodegenerative diseases participating in a chaplain-led
      spiritual life review interview and development of a spiritual legacy document
      (SLD). METHODS: Eligible participants were enrolled and completed baseline
      questionnaires. They were interviewed by a board-certified chaplain about
      spiritual influences, beliefs, practices, values, and spiritual struggles. An SLD
      was prepared for each participant, and one month follow-up questionnaires were
      completed. Two cases are summarized, and spiritual development themes are
      illustrated within a spiritual development framework. RESULTS: A total of 27
      patients completed baseline questionnaires and the interview; 24 completed the
      SLD, and 15 completed the follow-up questionnaire. Increases in SWB, religious
      coping, and QOL were detected. The majority maintained the highest (best) scores
      of negative religious coping, demonstrating minimal spiritual struggle.
      CONCLUSIONS: Despite the challenges of brain cancers and other neurodegenerative
      diseases, participants demonstrated improvements in SWB, positive religious
      coping, and QOL. Patient comments indicate that benefit is related to the
      opportunity to reflect on and integrate spiritual experiences and to preserve
      them for others. Research with a larger, more diverse sample is needed, as well
      as clinical applications for those too vulnerable to participate in longitudinal
      follow-up.

PMID- 25973268
TI  - Integrative nursing: application of principles across clinical settings.
AB  - While the essence of nursing has long been whole person (body, mind, and spirit)
      and whole system-focused, in reality the contemporary practice of nursing in many
      settings around the globe has become increasingly fragmented and de-stabilized.
      Nursing shortages in many parts of the world are significant, and hierarchies and
      bureaucracies often remove nurses from the point of care, be that the bedside,
      home, or clinic, replacing them with less skilled workers and filling their time
      with documentation and other administrative tasks. Integrative nursing is a
      framework for providing whole person/whole system care that is relationship-based
      and person-centered and focuses on improving the health and wellbeing of
      caregivers as well as those they serve. It is aligned with what is being called
      the "triple aim" in the United States-an effort focused on improving the patient
      experience (quality and satisfaction), improving the health of populations, and
      reducing the cost of care. The principles of integrative nursing offer clear and
      specific guidance that can shape and impact patient care in all clinical
      settings. 

PMID- 25973269
TI  - From research to reality: minimizing the effects of hospitalization on older
      adults.
AB  - This review examines ways to decrease preventable effects of hospitalization on
      older adults in acute care medical (non-geriatric) units, with a focus on the
      Israeli experience at the Rambam Health Care Campus, a large tertiary care
      hospital in northern Israel. Hospitalization of older adults is often followed by
      an irreversible decline in functional status affecting their quality of life and
      well-being after discharge. Functional decline is often related to avoidable
      effects of in-hospital procedures not caused by the patient's acute disease. In
      this article we review the literature relating to the recognized effects of
      hospitalization on older adults, pre-hospitalization risk factors, and
      intervention models for hospitalized older adults. In addition, this article
      describes an Israeli comprehensive research study, the Hospitalization Process
      Effects on Functional Outcomes and Recovery (HoPE-FOR), and outlines the design
      of a combined intervention model being implemented at the Rambam Health Care
      Campus. The majority of the reviewed studies identified preadmission personal
      risk factors and psychosocial risk factors. In-hospital restricted mobility,
      under-nutrition care, over-use of continence devices, polypharmacy, and
      environmental factors were also identified as avoidable processes. Israeli
      research supported the findings that preadmission risk factors together with in
      hospital processes account for functional decline. Different models of care have
      been developed to maintain functional status. Much can be achieved by
      interdisciplinary teams oriented to the needs of hospitalized elderly in making
      an impact on hospital processes and continuity of care. It is the responsibility
      of health care policy-makers, managers, clinicians, and researchers to pursue
      effective interventions to reduce preventable hospitalization-associated
      disability. 

PMID- 25973270
TI  - The human microbiota: the rise of an "empire".
AB  - The human body hosts rich and diverse microbial communities. Our microbiota
      affects the normal human physiology, and compositional changes might alter host
      homeostasis and, therefore, disease risk. The microbial community structure may
      sometimes occupy discrete configurations and under certain circumstances vary
      continuously. The ability to characterize accurately the ecology of human
      associated microbial communities became possible by advances in deep sequencing
      and bioinformatics analyses. 

PMID- 25973271
TI  - A Preliminary Study of Three-dimensional Sonographic Measurements of the Fetus.
AB  - OBJECTIVES: This study was aimed at establishing an ideal method for performing
      three-dimensional measurements of the fetus in order to improve the estimation of
      fetal weight. METHODS: The study consisted of two phases. Phase I was a
      prospective cross-sectional study performed between 28 and 40 weeks' gestation.
      The study population (n=110) comprised low-risk singleton pregnancies who
      underwent a routine third-trimester sonographic estimation of fetal weight. The
      purpose of this phase was to establish normal values for the fetal abdominal and
      head volumes throughout the third trimester. Phase II was a prospective study
      that included patients admitted for an elective cesarean section or for induction
      of labor between 38 and 41 weeks' gestation (n=91). This phase of the study
      compared the actual birth weight to two- (2D) and three-dimensional (3D)
      measurements of the fetus. Conventional 2D ultrasound fetal biometry was
      performed measuring the biparietal diameter (BPD), head circumference (HC),
      abdominal circumference (AC), and femur diaphysis length (FL). Volume estimates
      were computed utilizing Virtual Organ Computer-aided AnaLysis (VOCAL), and the
      correlation between measured volumes and actual neonatal weight was calculated.
      RESULTS: Overall, this longitudinal study consisted of 110 patients between 28
      and 41 weeks' gestation. Normal values were computed for the fetal abdomen and
      head volume throughout the third trimester. Ultrasound examination was performed
      within three days prior to delivery on 91 patients. A good correlation was found
      between birth weight and abdominal volume (r=0.77) and between birth weight and
      head volume (r=0.5). Correlation between bidimensional measurements and actual
      fetal weights was found to be comparable with previously published correlations.
      CONCLUSION: Volume measurements of the fetus may improve the accuracy of
      estimating fetal size. Additional studies using different volume measurement of
      the fetus are necessary.

PMID- 25973272
TI  - Central sensitization syndrome and the initial evaluation of a patient with
      fibromyalgia: a review.
AB  - In both primary care and consultative practices, patients presenting with
      fibromyalgia (FM) often have other medically unexplained somatic symptoms and are
      ultimately diagnosed as having central sensitization (CS). Central sensitization
      encompasses many disorders where the central nervous system amplifies sensory
      input across many organ systems and results in myriad symptoms. A pragmatic
      approach to evaluate FM and related symptoms, including a focused review of
      medical records, interviewing techniques, and observations, is offered here,
      giving valuable tools for identifying and addressing the most relevant symptoms.
      At the time of the clinical evaluation, early consideration of CS may improve the
      efficiency of the visit, reduce excessive testing, and help in discerning between
      typical and atypical cases so as to avoid an inaccurate diagnosis. Discussion of
      pain and neurophysiology and sensitization often proves helpful. 

PMID- 25973273
TI  - Cultural Perspectives on the Aftereffects of Combat Trauma: Review of a Community
      Study of Bedouin IDF Servicemen and Their Families.
AB  - Combat trauma may affect servicemen from indigenous, traditional communities in
      ways that warrant special attention. The Bedouins, who enlist in the Israel
      Defense Forces (IDF) voluntarily, represent a unique, closed, collectivist
      cultural minority, potentially in a predicament in light of ongoing
      sociopolitical events. This paper summarizes findings and lessons learned from a
      community study of Bedouin IDF servicemen and their families residing in Israel's
      Western Galilee. This is the only research endeavor to have addressed trauma
      exposure and posttraumatic reactions in this community. The sampling strategies
      and interview schedule were designed in consideration of participation barriers
      typical of hard-to-reach populations. Data collection followed an extended phase
      of liaising with key informants and building trust. Study limitations are
      discussed in terms of the challenges presented by this type of research.
      Interviews conducted with 317 men, 129 wives, and 67 mothers revealed high levels
      of trauma exposure and posttraumatic stress disorder (PTSD) in the men, and
      related distress in wives and mothers, but not in the children. The role of
      aggression in mediating the impact of PTSD and concepts such as shame, the loss
      of personal resources, and beliefs about retribution are highlighted as key
      issues for a culturally relevant understanding of traumatized indigenous
      communities. 

PMID- 25973274
TI  - Older primary care patients' attitudes and willingness to screen for dementia.
AB  - Objective. To understand older primary care patients' perceptions of the risks
      and benefits of dementia screening and to measure the association between
      attitudes and screening behaviors. Methods. Eligible patients completed the
      Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM
      PC) questionnaire and then were asked to undergo dementia screening by a
      telephone screening instrument. Results. Higher scores on the PRISM-PC
      questionnaire items that measure attitudes about benefits of screening were
      associated with decreased odds of refusing screening. Participants who refused
      screening had significantly lower PRISM-PC questionnaire scores on the items that
      measure perceived benefits compared to those who agreed to screening.
      Participants who refused screening were less likely to agree on screening for
      other conditions, such as depression and cancer. Participants who know someone
      with Alzheimer's disease (AD) were less likely to refuse screening. Discussion.
      Patients' attitudes about the benefits of dementia screening are associated with
      their acceptance of dementia screening. 

PMID- 25973275
TI  - Epidemiology of neuromyelitis optica in the world: a systematic review and meta
      analysis.
AB  - Background. Neuromyelitis optica (Devic's disease) is a severe autoimmune
      inflammatory disorder of the central nervous system. Epidemiological aspects of
      NMO have not been systemically reviewed. In this study we systematically reviewed
      and assessed the quality of studies reporting the incidence and/or prevalence of
      NMO across the world. Methods. A comprehensive literature search using MEDLINE,
      EMBASE, and Web of Science for the terms "Neuromyelitis optica," "devic disease,"
      "incidence," "prevalence," and "epidemiology" was conducted on January 31, 2015.
      Study quality was assessed using an assessment tool based on recognized
      guidelines and designed specifically for this study. Results. A total of 216
      studies were initially identified, with only 9 meeting the inclusion criteria.
      High level of heterogeneity amongst studies precluded a firm conclusion.
      Incidence data were found in four studies and ranged from 0.053 per 100,000 per
      year in Cuba to 0.4 in Southern Denmark. Prevalence was reported in all studies
      and ranged from 0.51 per 100,000 in Cuba to 4.4 in Southern Denmark. Conclusion.
      This review reveals the gaps that still exist in the epidemiological knowledge of
      NMO in the world. Published studies have different qualities and methodology
      precluding a robust conclusion. Future researches focusing on epidemiological
      features of NMO in different nations and different ethnic groups are needed. 

PMID- 25973276
TI  - Prostate cancer patients' refusal of cancer-directed surgery: a statewide
      analysis.
AB  - Introduction. Prostate cancer is the most common cancer among men in USA. The
      surgical outcomes of prostate cancer remain inconsistent. Barriers such as
      socioeconomic factors may play a role in patients' decision of refusing
      recommended cancer-directed surgery. Methods. The Nebraska Cancer Registry data
      was used to calculate the proportion of prostate cancer patients recommended the
      cancer-directed surgery and the surgery refusal rate. Multivariate logistic
      regression was applied to analyze the socioeconomic indicators that were related
      to the refusal of surgery. Results. From 1995 to 2012, 14,876 prostate cancer
      patients were recommended to undergo the cancer-directed surgery in Nebraska, and
      576 of them refused the surgery. The overall refusal rate of surgery was 3.9%
      over the 18 years. Patients with early-stage prostate cancer were more likely to
      refuse the surgery. Patients who were Black, single, or covered by
      Medicaid/Medicare had increased odds of refusing the surgery. Conclusion.
      Socioeconomic factors were related to the refusal of recommended surgical
      treatment for prostate cancer. Such barriers should be addressed to improve the
      utilization of surgical treatment and patients' well-being. 

PMID- 25973277
TI  - SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma.
AB  - Breast cancer (BC) is the second most common cancer diagnosed in American women
      and is also the second leading cause of cancer death in women. Research has
      focused heavily on BC metastasis. Multiple signaling pathways have been
      implicated in regulating BC metastasis. Our knowledge of regulation of BC
      metastasis is, however, far from complete. Identification of new factors during
      metastasis is an essential step towards future therapy. Our labs have focused on
      Semaphorin 6D (SEMA6D), which was implicated in immune responses, heart
      development, and neurogenesis. It will be interesting to know SEMA6D-related
      genomic expression profile and its implications in clinical outcome. In this
      study, we examined the public datasets of breast invasive carcinoma from The
      Cancer Genome Atlas (TCGA). We analyzed the expression of SEMA6D along with its
      related genes, their functions, pathways, and potential as copredictors for BC
      patients' survival. We found 6-gene expression profile that can be used as such
      predictors. Our study provides evidences for the first time that breast invasive
      carcinoma may contain a subtype based on SEMA6D expression. The expression of
      SEMA6D gene may play an important role in promoting patient survival, especially
      among triple negative breast cancer patients. 

PMID- 25973278
TI  - Oral squamous cell carcinoma arising in a patient after hematopoietic stem cell
      transplantation with bisphosphonate-related osteonecrosis of the jaws.
AB  - A 55-year-old man with a history of acute myeloid leukaemia treated with
      hematopoietic stem cell transplantation and with a 5-year history of
      bisphosphonate-related osteonecrosis of the jaws, following 12 cycles of
      intravenous zoledronic acid therapy, presented in December 2009 with a history of
      increasingly severe unilateral lower jaw pain. Oral examination revealed, as
      previously, exposed bone in the left mandible, but also a new exophytic mass on
      the lower-left buccal mucosa. Biopsy confirmed a diagnosis of oral squamous cell
      carcinoma. To the best of our knowledge, this is the first report of an oral
      squamous cell carcinoma that appeared adjacent to an area of osteochemonecrosis. 

PMID- 25973279
TI  - A case of neglected bilateral anterior shoulder dislocation: a rare entity with
      unusual mechanism of injury.
AB  - Bilateral shoulder dislocations are rare, and if they occurred, posterior type of
      dislocations is common. Bilateral anterior shoulder dislocations are very rare
      and occur due to trauma with unique mechanism of injury. We report a case of
      unreduced simultaneous bilateral anterior dislocations of shoulder without
      associated fractures in a forty-year-old man following a unique mechanism of
      injury; both hands of the patient were pulled from either side. To the best of
      our knowledge, this unusual mechanism of injury has not been reported in the
      literature. 

PMID- 25973280
TI  - Acute osteomyelitis of the symphysis pubis after inguinal hernia surgery.
AB  - Osteomyelitis of pubic symphysis is infectious inflammatory condition of the
      symphysis pubis and rare complication of surgery around inguinal and groin
      region. It should be kept in mind in the differential diagnosis of lower pelvic
      pain and should be sought in cases of pelvic insufficiency fractures. Herein, we
      present a case of a 55-year-old man with osteomyelitis of the symphysis pubis
      following inguinal hernia surgery for diagnosis and management of this rare
      condition. 

PMID- 25973281
TI  - Idiopathic bilateral adrenal hemorrhage in a 63-year-old male: a case report and
      review of the literature.
AB  - Adrenal hemorrhage is a largely uncommon condition typically caused by a number
      of factors including infection, MI, CHF, anticoagulants, trauma, surgery, and
      antiphospholipid syndrome. Yet, idiopathic bilateral hemorrhage is rare. The
      authors present a case of a 63-year-old male who presented with abdominal pain
      that was eventually diagnosed as bilateral adrenal hemorrhages due to an unknown
      origin. Abdominal CT revealed normal adrenal glands without enlargement, but an
      MRI displayed enlargement due to hemorrhage in both adrenals. There was no known
      cause; the patient had not suffered from an acute infection and was not on
      anticoagulants, and the patient's history did not reveal any of the other known
      causative factors. The case underscores the importance of keeping bilateral
      adrenal hemorrhages on the list of differentials even when a cause is not
      immediately clear. It also raises the question of whether CT is the most
      sensitive test in the diagnosis of adrenal hemorrhage and whether the diagnostic
      approach should place greater weight on MRI. The case highlights the need for
      prompt therapy with steroids once bilateral hemorrhage is suspected to avert the
      development or progression of adrenal insufficiency. 

PMID- 25973282
TI  - Current status of sodium bicarbonate in coronary angiography: an updated
      comprehensive meta-analysis and systematic review.
AB  - This systematic review with meta-analysis sought to determine comparison of
      efficacy and safety of hydration with sodium bicarbonate versus sodium chloride
      on contrast induced nephropathy and clinical outcomes. We searched major
      electronic databases for studies in randomized controlled trials. A value of P <
      0.1 for Q test or I (2) > 50% indicated significant heterogeneity between the
      studies. Literature search of all databases retrieved 650 studies. 29 studies
      enrolled in meta-analysis. Pooled analysis indicated about the incidence of CIN
      (OR of 0.718; 95% CI: 0.60 to 0.85; P = 0.000), requirement of hemodialysis (OR
      of 1.00; 95% CI: 0.49 to 2.01; P = 0.9), mean changes of serum creatinine (WMD of
      2.321; 95% CI: 1.995 to 2.648; P = 0.000), length of hospital stays (WMD of 
      0.774; 95% CI: -1.65 to 0.10; P = 0.08), major adverse cardiovascular events (OR
      = 1.075, 95% CI: 0.59 to 1.95; P = 0.8), and mortality (OR of 0.73; 95% CI: 0.42
      to 1.26; P = 0.2). Overall, hydration with sodium bicarbonate could significantly
      reduce CIN and the length of hospital stay compared to sodium chloride. In
      addition NAC added as a supplement to sodium bicarbonate could increase
      prophylactic effects against nephropathy. 

PMID- 25973283
TI  - Development of a method to detect three monohydroxylated polycyclic aromatic
      hydrocarbons in human urine by liquid chromatographic tandem mass spectrometry.
AB  - A liquid chromatographic tandem mass spectrometry method (LC-MS/MS) for the
      simultaneous determination of 1-hydroxypyrene (1-OHP), 3-hydroxybenzo[a]pyrene (3
      OHBaP), and 3-hydroxybenz[a]anthracene (3-OHBaA) in human urine has been
      developed. With the exception of 3-OHBaP at a low spiking level, the average
      recoveries were greater than 80%. The method has good accuracy (72.1-107.7%) and
      reproducibility (1.8-11.4%) and was successfully used to study the uptake of
      pyrene, benzo[a]pyrene, and benzo[a]anthracene from cigarette smoke. The results
      indicated that urinary 1-OHP concentration in the smoking group (66.58 +/- 70.91
      ng/g creatinine) was higher than that observed in the nonsmoking group (58.16 +/-
      49.48 ng/g creatinine). Urinary 3-OHBaA concentrations in nonsmokers and smokers
      with 8 mg and 10 mg tar cigarettes were 10.98 +/- 4.39 ng/g creatinine, 11.01 +/-
      13.30 ng/g creatinine, and 9.17 +/- 12.89 ng/g creatinine, respectively. Urinary
      3-OHBaP concentrations in nonsmokers and smokers with 8 mg and 13 mg tar
      cigarettes were 1.30 +/- 0.20 ng/g creatinine, 2.83 +/- 1.78 ng/g creatinine, and
      6.00 +/- 4.44 ng/g creatinine, respectively. Urinary 1-OHP levels exhibited a
      significant correlation with BaP yield in cigarette smoke under the Canadian
      intense smoking condition (y = 3.5563x + 30.171, R (2) = 0.9916, n = 227). 

PMID- 25973284
TI  - Acute necrotizing encephalopathy in an adult.
AB  - Acute necrotizing encephalopathy (ANE) is a rapidly progressing neurologic
      disorder that occurs in children after common viral infections of the respiratory
      or gastrointestinal systems. This disease is commonly seen in East Asia. Normal
      healthy infants and children can get affected. The condition carries a poor
      prognosis with high morbidity and mortality rates. We report here a case of a 23
      year-old female with ANE and describe its neuroimaging findings. Magnetic
      resonance imaging examination performed showed symmetric lesions involving the
      thalami, brainstem, and cerebellum. 

PMID- 25973285
TI  - Hydronephrosis as an unusual cause of acute pancreatitis.
AB  - Acute pancreatitis is an inflammatory disease of the pancreas. The most common
      cause of acute pancreatitis is gallstone impacting the distal common bile
      pancreatic duct (38%) and alcoholism (36%). There have been a few reports in the
      literature of acute pancreatitis associated with an obstructed urinary system.
      This case describes a 38-year-old male with acute pancreatitis occurring in the
      setting of hydronephrosis. A magnetic resonance cholangiopancreaticography (MRCP)
      showed right-sided severe hydronephrosis pushing the duodenum and head of
      pancreas anteriorly, thus obliterating distal segment of the common bile duct.
      There were also multiple right renal stones causing ureteral obstruction and
      hydronephrosis. Right nephrostomy was performed to release bile duct obstruction.
      However, sepsis and disseminated intravascular coagulation developed as a
      complication of acute pancreatitis, and the patient passed away. Although
      gallstone and alcoholism are the most common causes of acute pancreatitis, other
      causes should always be considered. Physicians should be aware of right
      hydronephrosis as one of the possible causes of acute pancreatitis in their
      workup of patients. 

PMID- 25973286
TI  - A case of metastatic rectal squamous cell carcinoma initially diagnosed as lung
      cancer.
AB  - Squamous cell carcinoma (SCC) of the rectum is extremely rare with a reported
      incidence of only 0.025-0.1% of all colorectal tumors. The patient was a 68-year
      old man who presented with fatigue, dry cough, shortness of breath, and
      unintentional weight loss. A chest CT revealed a left suprahilar mass suspected
      to be lung cancer and an initial diagnosis of primary lung cancer was made.
      However, fluorodeoxyglucose positron emission tomography and computed tomography
      (FDG-PET/CT) exam revealed an intensely hypermetabolic rectal mass which turned
      out to be rectal squamous cell carcinoma. This is the first report that shows FDG
      PET/CT images of rectal squamous cell carcinoma metastasis to the skin, muscle,
      bone, and lung. Use of PET/CT in the initial diagnosis of non-resectable rectal
      cancers may avoid unnecessary surgery. 

PMID- 25973287
TI  - Synovial hemangioma in the knee: MRI findings.
AB  - Synovial hemangiomas are rare benign tumors of vascular origin. A 23-year-old boy
      presented with knee pain and swelling. The boy had developed symptoms 18-months
      earlier. He was diagnosed with synovial hemangioma based on magnetic resonnance
      imaging examination and histopathologic findings of the arthroscopic biopsy
      tissue. We present the magnetic resonance imaging and histopathologic findings of
      synovial hemangioma of the knee. 

PMID- 25973289
TI  - A rare coronary artery anomaly: origin of all three coronary arteries from the
      right sinus of valsalva.
AB  - Left anterior descending (LAD) artery and left circumflex (LCx) coronary artery
      originating separately from the right sinus of valsalva is exceptionally rare and
      very few cases have been reported in the literature. Congenital coronary artery
      anomalies are generally incidental, uncommon, and asymptomatic. Some can cause
      severe potentially life-threatening symptoms such as myocardial ischemia and
      sudden cardiac death. The aberrant vessels that pass between the aorta and the
      pulmonary trunk pose a risk of sudden cardiac death, particularly if the vessel
      supplies the left coronary artery network. The electrocardiographically gated
      multi-detector computed tomography (MDCT) allows accurate and non-invasive
      depiction of coronary artery anomalies including origin, course, and termination.
      We report here a rare case of all three coronary arteries separately originating
      from the right coronary sinus, which was detected with MDCT. 

PMID- 25973288
TI  - Cross-sectional Imaging Features of Primary Retroperitoneal Tumors and Their
      Subsequent Treatment.
AB  - Basically malignant tumors in the retroperitoneal region arise from a
      heterogeneous group of tissues: mesodermal, neurogenic, germ cell, and lymphoid.
      Although rare, benign tumors and cystic masses can be also encountered in
      retroperitoneal space. Developments in computed tomography (CT) and magnetic
      resonance imaging (MRI) have contributed to both diagnosis and staging of the
      retroperitoneal tumors. High spatial resolution and superiority in calcification
      make CT indispensable; on the other hand, MRI has a better soft-tissue contrast
      resolution which is essential for the assessment of vascular invasion and tissue
      characterization. The aim of this article is to review the CT and MRI features of
      retroperitoneal tumors and their subsequent management. 

PMID- 25973290
TI  - Myths about Publishing in an Open Access Journal.

PMID- 25973291
TI  - Circular RNAs in cancer: novel insights into origins, properties, functions and
      implications.
AB  - Circular RNAs (circRNAs) are a large class of RNAs that, unlike linear RNAs, form
      covalently closed continuous loops and have recently shown huge capabilities as
      gene regulators in mammals. These circRNAs mainly arise from exons or introns,
      and are differentially generated by back splicing or lariat introns.
      Interestingly, they are found to be enormously abundant, evolutionally conserved
      and relatively stable in cytoplasm. These features confer numerous potential
      functions to circRNAs, such as acting as microRNA (miRNA) sponges, binding to RNA
      associated proteins to form RNA-protein complexes and then regulating gene
      transcription. Importantly, circRNAs associate with cancer-related miRNAs and the
      circRNA-miRNA axes are involved in cancer-related pathways. Some synthetic
      circRNAs have shown the remarkable anti-cancer effects. Though circRNAs are
      ancient molecules, the huge therapeutic potentials of circRNAs are recently being
      discovered from the laboratory to the clinic. Here, we review the current
      understanding of the roles of circRNAs in cancers and the potential implications
      of circRNAs in cancer targeted therapy. 

PMID- 25973293
TI  - ART1 promotes starvation-induced autophagy: a possible protective role in the
      development of colon carcinoma.
AB  - Autophagy plays a protective role in colorectal carcinoma. Arginine ADP
      ribosyltransferase 1 (ART1) is an important mono-ADP-ribose transferase, which
      has been shown to play a role in biological processes such as proliferation and
      invasion of cancer cells. Interestingly, the role of ART1 in the regulation of
      autophagy is still not clear. We examined effects of overexpression or knockdown
      of ART1 by lentiviral transfection on starvation-induced autophagy of colon
      carcinoma CT26 cell lines in vivo and in vitro. The formation of autophagosome
      was detected by electron microscopy, acridine orange staining and expression of
      LC3 B. The molecular contributions of ART1 in regulation of autophagy were
      detected by western blotting or by co-immunoprecipitation. Additionally,
      inhibitors were used to study further the signaling pathway of ART1 in the
      regulation of autophagy. CCK8 assay, plate cloning assay, soft agar assay,
      examination of subcutaneous transplanted carcinoma in BALB/c mice, flow cytometry
      and Hoechst33342 staining were used to assess survival and apoptotic ability when
      starvation-induced autophagy modulated by ART1 was inhibited by 3-MA.
      Overexpression of ART1 promoted starvation-induced autophagy, which related to
      increases in the expression of Rac1, NF-kappaB, PARP-1, LKB1 and p-AMPK and a
      decrease in the expression of p-P70S6K. Correspondingly, knockdown of ART1 caused
      the opposite effects. ART1 also interacted with integrin alpha7. Additionally,
      changes of protein expressions were further validated following inhibition of
      Rac1 and PARP-1 in the starvation-induced ART1-GFP CT26 cells. Inhibition of ART1
      stimulated starvation-induced autophagy restrained the growth and promoted
      apoptosis. ART1 is thus relevant in starvation-induced autophagy in colorectal
      carcinoma and may play essential roles in therapeutic anticancer strategies. 

PMID- 25973292
TI  - Nitric oxide is the key mediator of death induced by fisetin in human acute
      monocytic leukemia cells.
AB  - Nitric oxide (NO) has been shown to be effective in cancer chemoprevention and
      therefore drugs that help generate NO would be preferable for combination
      chemotherapy or solo use. This study shows a new evidence of NO as a mediator of
      acute leukemia cell death induced by fisetin, a promising chemotherapeutic agent.
      Fisetin was able to kill THP-1 cells in vivo resulting in tumor shrinkage in the
      mouse xenograft model. Death induction in vitro was mediated by an increase in NO
      resulting in double strand DNA breaks and the activation of both the extrinsic
      and the intrinsic apoptotic pathways. Double strand DNA breaks could be reduced
      if NO inhibitor was present during fisetin treatment. Fisetin also inhibited the
      downstream components of the mTORC1 pathway through downregulation of levels of
      p70 S6 kinase and inducing hypo-phosphorylation of S6 Ri P kinase, eIF4B and
      eEF2K. NO inhibition restored phosphorylation of downstream effectors of mTORC1
      and rescued cells from death. Fisetin induced Ca(2+) entry through L-type Ca(2+)
      channels and abrogation of Ca(2+) influx reduced caspase activation and cell
      death. NO increase and increased Ca(2+) were independent phenomenon. It was
      inferred that apoptotic death of acute monocytic leukemia cells was induced by
      fisetin through increased generation of NO and elevated Ca(2+) entry activating
      the caspase dependent apoptotic pathways. Therefore, manipulation of NO
      production could be viewed as a potential strategy to increase efficacy of
      chemotherapy in acute monocytic leukemia. 

PMID- 25973294
TI  - Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination
      with MT1-MMP and Rho GTPases.
AB  - Podoplanin overexpression has been reported in various cancers, however, the
      precise mechanism for podoplanin to promote tumor progression remains elusive. In
      the present study, podoplanin overexpression was found associated with
      invasiveness both in OSCC tissues and cell lines. Moreover, the cell invasiveness
      increased with forced podoplanin expression and decreased when podoplanin was
      knockdown, indicating podoplanin-mediated cell invasion during OSCC progression.
      To further identify the role of podoplanin in tumor invasion, cell spreading and
      immunofluorescence assay were performed firstly. It was found that podoplanin
      knockdown caused an impaired cell spreading with reduced filopodia and the
      premature assembly of stress fibers while podoplanin overexpression induced an
      increase in cellular protrusions and stress fibers with extensive parallel
      bundles. Then, pull-down assays revealed forced podoplanin expression increased
      Cdc42 activity and reduced RhoA activity while podoplanin knockdown decreased
      Cdc42 and increased RhoA markedly. Moreover, a hierarchy of crosstalk between
      RhoA and Cdc42 was confirmed in podoplanin-mediated cell motility. On the other
      hand, a significant correlation between podoplanin and MT1-MMP expression in
      OSCCs was found both in vivo and in vitro, co-located in invasive cells and
      cellular protrusions. Furthermore, our data showed MT1-MMP knockdown
      significantly blocked the upregulation of cell motility by forced podoplanin
      expression, indicating that MT1-MMP played a role in podoplanin-mediated tumor
      invasion. To further confirm the interaction between RhoA/Cdc42 complex, MT1-MMP
      and podoplanin, co-precipitation experiments were performed. Both the co
      precipitation of podoplanin with MT1-MMP and the podoplanin-induced specific
      binding of MT1-MMP to Cdc42 were found, and immunofluorescence revealed the co
      location of podoplanin, MT1-MMP and Cdc42 at the plasma membrane and filopodia
      induced an increase in cellular protrusion and stress fibers formation. Moreover,
      MT1-MMP inhibition could partly rescue the increase of Cdc42 activity caused by
      forced podoplanin expression. Taken together, our data demonstrated a hierarchy
      of crosstalk between RhoA and Cdc42 was involved in podoplanin-mediated
      cytoskeleton remodeling and invasion; the co-location and co-ordination of
      podoplanin, Cdc42 and MT1-MMP in the invadopodia might induce cytoskeleton
      remodeling, ECM degradation and tumor invasion, while podoplanin-induced EMT may
      not be indispensible during OSCC progression. 

PMID- 25973295
TI  - Downregulation of ER-alpha36 expression sensitizes HER2 overexpressing breast
      cancer cells to tamoxifen.
AB  - Tamoxifen provided a successful treatment for ER-positive breast cancer for many
      years. However, HER2 overexpressing breast cancer cells respond poorly to
      tamoxifen therapy presumably by pass. The molecular mechanisms underlying
      development of tamoxifen resistance have not been well established. Recently, we
      reported that breast cancer cells with high levels of ER-alpha36, a variant of ER
      alpha, were resistant to tamoxifen and knockdown of ER-alpha36 expression in
      tamoxifen resistant cells with the shRNA method restored tamoxifen sensitivity,
      indicating that gained ER-alpha36 expression is one of the underlying mechanisms
      of tamoxifen resistance. Here, we found that tamoxifen induced expression of ER
      alpha36-EGFR/HER2 positive regulatory loops and tamoxifen resistant MCF7 cells
      (MCF7/TAM) expressed enhanced levels of the loops. Disruption of the ER-alpha36
      EGFR/HER2 positive regulatory loops with the dual tyrosine kinase inhibitor
      Lapatinib or ER-alpha36 down-regulator Broussoflavonol B in tamoxifen resistant
      MCF7 cells restored tamoxifen sensitivity. In addition, we also found both
      Lapatinib and Broussoflavonol B increased the growth inhibitory activity of
      tamoxifen in tumorsphere cells derived from MCF7/TAM cells. Our results thus
      demonstrated that elevated expression of the ER-alpha36-EGFR/HER2 loops is one of
      the mechanisms by which ER-positive breast cancer cells escape tamoxifen therapy.
      Our results thus provided a rational to develop novel therapeutic approaches for
      tamoxifen resistant patients by targeting the ER-alpha36-EGFR/HER2 loops. 

PMID- 25973296
TI  - Role of miR-100 in the radioresistance of colorectal cancer cells.
AB  - The prognosis of radioresistant colorectal cancer (CRC) is generally poor.
      Abnormal expression of microRNAs (miRNAs) is involved in the radiosensitivity of
      various tumor cells as these RNAs regulate biological signaling pathways.
      However, radioresistance-associated miRNAs in CRC have not yet been identified.
      In this study, we filtered out HCT116 and CCL-244 from seven CRC cell lines that
      showed the highest difference in radiosensitivity in a clonogenic assay. MiRNA
      sequencing identified 33 differentially expressed miRNAs (13 up-regulated and 20
      down-regulated) in CCL-244 and 37 in HCT116 (20 up-regulated and 17 down
      regulated) cells. MiR-100 was significantly down-regulated in CCL-244 cells after
      X-ray irradiation but not in HCT116 cells. Quantitative real-time PCR showed that
      the expression of miR-100 in CRC tissues was significantly lower than that in
      normal tissues. Thus, miR-100 seems to be involved in the radioresistance of CCL
      244 cells. MiR-100 up-regulation sensitized CCL-244 cells to X-ray irradiation,
      which probably led to apoptosis and DNA double-strand breaks in these. In
      conclusion, to our knowledge, this is the first study to show that miR-100 may
      play an important role in regulating the radiosensitivity of CRC, and it may act
      as a new clinical target for CRC radiotherapy. 

PMID- 25973297
TI  - Prominin-1 (CD133, AC133) and dipeptidyl-peptidase IV (CD26) are indicators of
      infinitive growth in colon cancer cells.
AB  - Advanced colorectal cancer is characterized by uncontrolled growth and resistance
      against anti-cancer agents, including ErbB inhibitors. Recent data suggest that
      cancer stem cells (CSC) are particularly resistant. These cells may reside within
      a CD133+ fraction of the malignant cells. Using HCT116 cells we explored the role
      of CD133 and other CSC markers in drug resistance in colon cancer cells. CD133+
      cells outnumbered CD133- cells over time in long-term culture. Both populations
      displayed the KRAS mutation 38G > A and an almost identical target profile,
      including EGFR/ErbB1, ErbB2, and ErbB4. Microarray analyses and flow cytometry
      identified CD26 as additional CSC marker co-expressed on CD133+ cells. However,
      knock-down of CD133 or CD26 did not affect short-term growth of HCT116 cells, and
      both cell-populations were equally resistant to various targeted drugs except
      irreversible ErbB inhibitors, which blocked growth and ERK1/2 phosphorylation in
      CD133- cells more efficiently than in CD133+ cells. Moreover, the MEK inhibitor
      AS703026 was found to overcome resistance against ErbB blockers in CD133+ cells.
      Together, CD133 and CD26 are markers of long-term growth and resistance to ErbB
      blockers in HCT116 cells, which may be mediated by constitutive ERK activity. 

PMID- 25973298
TI  - Minocycline attenuates hypoxia-inducible factor-1alpha expression correlated with
      modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro
      and in vivo studies.
AB  - Hypoxia-inducible factor (HIF)-1alpha is the key cellular survival protein under
      hypoxia, and is associated with tumor progression and angiogenesis. We have
      recently shown the inhibitory effects of minocycline on ovarian tumor growth
      correlated with attenuation of vascular endothelial growth factor (VEGF) and
      herein report a companion laboratory study to test if these effects were the
      result of HIF-1alpha inhibition. In vitro, human ovarian carcinoma cell lines
      (A2780, OVCAR-3 and SKOV-3) were utilized to examine the effect of minocycline on
      HIF-1 and its upstream pathway components to elucidate the underlying mechanism
      of action of minocycline. Mice harboring OVCAR-3 xenografts were treated with
      minocycline to assess the in vivo efficacy of minocycline in the context of HIF
      1. Minocycline negatively regulated HIF-1alpha protein levels in a concentration
      dependent manner and induced its degradation by a mechanism that is independent
      of prolyl-hydroxylation. The inhibition of HIF-1alpha was found to be associated
      with up-regulation of endogenous p53, a tumor suppressor with confirmed role in
      HIF-1alpha degradation. Further studies demonstrated that the effect of
      minocycline was not restricted to proteasomal degradation and that it also caused
      down-regulation of HIF-1alpha translation by suppressing the AKT/mTOR/p70S6K/4E
      BP1 signaling pathway. Minocycline treatment of mice bearing established ovarian
      tumors, led to suppression of HIF-1alpha accompanied by up-regulation of p53
      protein levels and inactivation of AKT/mTOR/p70S6K/4E-BP1 pathway. These data
      reveal the therapeutic potential of minocycline in ovarian cancer as an agent
      that targets the pro-oncogenic factor HIF-1alpha through multiple mechanisms. 

PMID- 25973299
TI  - High-level SAE2 promotes malignant phenotype and predicts outcome in gastric
      cancer.
AB  - BACKGROUND: The SUMO pathway has been shown to play an important role in
      tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating
      Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis.
      METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and
      immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel
      in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell
      growth, colony formation, migration and invasion were also explored by CCK8
      assay, colony formation experiment, transwell chamber assay with or without
      matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis.
      RESULTS: SAE2 was markedly overexpressed in GC cell lines and primary tumor
      samples of GC, and significantly correlated with deeper tumor depth, distant
      metastasis, higher pathological stage and stratified survival in human GC. SAE2
      positivity was independently associated with a worse outcome in multivariate
      analysis. Knockdown of SAE2 expression inhibited the proliferation, migration,
      and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro
      results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced
      the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was
      significantly associated with the higher expression of c-MYC in primary GC
      tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2
      resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls.
      CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the
      aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.

PMID- 25973300
TI  - Cisplatin loaded albumin mesospheres for lung cancer treatment.
AB  - The low solubility of cisplatin in aqueous solution limits the treatment
      effectiveness and the application of cisplatin in various kinds of drug-eluting
      devices. Although cisplatin has a high solubility in Dimethyl sulfoxide (DMSO),
      the toxicity of cisplatin can be greatly reduced while dissolved in DMSO. In this
      study, the solid powder of cisplatin-loaded albumin mesospheres (CDDP/DMSO-AMS),
      in a size range of 1 to 10 um, were post-loaded with cisplatin and showed high
      cisplatin content (16% w/w) and effective cytotoxicity to lung cancer cells.
      Cisplatin were efficiently absorbed into the albumin mesospheres (AMS) in DMSO
      and, most importantly, the toxicity of cisplatin was remained at 100% after the
      loading process. This CDDP/DMSO-AMS was designed for the intratumoral injection
      through the bronchoscopic catheter or dry powder inhalation (DPI) due to its high
      stability in air or in solution. This CDDP/DMSO-AMS showed a fast cisplatin
      release within 24 hours. In the in vitro study, CDDP/DMSO-AMS showed high
      effectiveness on killing the lung cancer cells including the non-small cell lung
      cancer (NCL-H23 and A549), malignant mesothelioma (CRL-2081) and the mouse lung
      carcinoma (Lewis lung carcinoma) cell lines. The albumin based mesospheres
      provide an ideal loading matrix for cisplatin and other metal-based drugs due to
      the high swelling degree and fast uptake rate in the organic solvents with high
      polarity. In addition, to investigate the effects of polysaccharides, such as
      chitosan and chondroitin, on enhancing loading efficiency and lasting
      cytotoxicity of cisplatin, the polysaccharide-modified albumin mesospheres were
      synthesized and loaded with cisplatin in this study. 

PMID- 25973301
TI  - VEGF-C-VEGFR3/Flt4 axis regulates mammary tumor growth and metastasis in an
      autocrine manner.
AB  - PURPOSE: Lymphangiogenic factors, such as vascular endothelial growth factor-C
      (VEGF-C) and VEGFC-D, and their receptor, VEGF receptor-3 (VEGFR3), play a
      pivotal role in the promotion of metastasis to regional lymph nodes. In the
      present study we explored the role of VEGF-C as an autocrine growth factor for
      breast cancer cells. METHODS: We examined the expression of VEGF-C and VEGFR3 in
      mammary tumor cells lines and examined whether blocking the VEGF-C-VEGFR3/Flt4
      pathway using a VEGFR3 antagonist would inhibit proliferation of mammary tumor
      cells resulting in a decrease in tumor growth and metastasis. RESULTS: We report
      expression of VEGF-C and its receptor VEGFR3 by mammary tumor cells, and their
      association with aggressiveness. Inhibition of VEGF-C-VEGFR3/Flt4 in mammary
      tumor cells decreased their proliferation and survival. Mammary tumor bearing
      mice treated with a VEGFR3 antagonist showed a significant decrease in tumor
      growth and the extent of spontaneous and experimental lung metastases.
      CONCLUSION: These findings demonstrate the VEGF-C-VEGFR3/Flt4 autocrine signaling
      pathway regulates mammary tumor cell survival and proliferation and that
      neutralization of VEGFR3 signaling might lead to development of a novel
      therapeutic approach for malignant breast cancer.

PMID- 25973302
TI  - Midkine as a potential diagnostic marker in epithelial ovarian cancer for
      cisplatin/paclitaxel combination clinical therapy.
AB  - The paclitaxel/cisplatin combination therapy commonly is used as the first-line
      treatment for advanced ovarian cancer patients. Midkine (MK), known as a novel
      tumor biomarker, has been elevated in the serum of patients with epithelial
      ovarian cancer (EOC). In this study, we aimed to detect the expression of MK in
      EOC tissues and evaluate clinical value of MK in diagnosis and therapy of EOC. We
      perform immunohistochemistry analysis to detect MK in EOC sample with
      postoperative platinum/paclitaxel combination therapy, we found that 71.4% (85 in
      119 samples) of these samples were MK positive (> 10% of the cells were stained),
      and the expression of MK was significantly associated with disease histology (P =
      0.038) as well as differentiation grade (P < 0.001). Moreover, MK positive
      samples show much more sensitive to cisplatin/paclitaxel combination therapy,
      compared with MK negative samples (P = 0.029). Those results indicated that MK
      expression might correlate with paclitaxel and/or cisplatin cytotoxicity in
      clinical therapy of EOC. Then, we evaluated the sensitivity to cisplatin and
      paclitaxel in 5 ovarian cancer cell lines (ES2, A2870, HO-8910, SKOV3 and SW626),
      and ES2, the highest MK expression among those cell lines, show the most
      sensitive to paclitaxel and cisplatin. Further, we confirmed this correlation
      between MK and paclitaxel and/or cisplatin cytotoxicity with the gain- and lost-
      of function. Finally, we demonstrated that MK enhanced the cytotoxicity of
      paclitaxel and/or cisplatin by accumulated cisplatin and paclitaxel through
      inhibited the expression of multidrug resistance-associated protein 3 (MRP3). In
      conclusion, MK could be an effective biomarker in diagnosis and therapy of EOC,
      especially for the drug selection at the time of initial diagnosis. 

PMID- 25973303
TI  - Inhibition of autophagy enhances the anticancer activity of bortezomib in B-cell
      acute lymphoblastic leukemia cells.
AB  - B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging disease to
      treat in adults because of the high rates of relapse and refractory. Bortezomib,
      as a proteasome inhibitor, exerts obvious cytotoxicity against ALL cells and
      increases the sensitivity of ALL cells to conventional chemotherapeutic agents.
      We observed that bortezomib inhibited proliferation, induced apoptosis, arrested
      the cell cycle and induced autophagy in the Nalm-6 cell line and CD34(+) primary
      cells. Additionally, we demonstrated that bortezomib promoted the disruption of
      the Bcl-2/Beclin-1 complex and increased the formation of the Beclin-1/PI3KC3
      complex, leading to the initiation of autophagy. Autophagy inhibitors were
      employed in this study, and we found that autophagy inhibitors enhanced the anti
      ALL activity of bortezomib. Taken together, these results revealed that autophagy
      protected B-ALL cells against the cytotoxicity of bortezomib and, in combination
      with autophagy inhibitors, can enhance the anticancer effects of bortezomib. 

PMID- 25973304
TI  - Epigenetic silencing BCL6B induced colorectal cancer proliferation and metastasis
      by inhibiting P53 signaling.
AB  - BCL6B, a homologue of BCL6, has been reported to be frequently methylated in
      human gastric cancer. The epigenetic change and the function of BCL6B remains to
      be elucidated in colorectal cancer. 7 colorectal cancer cell lines (RKO, HT-29,
      DLD1, LOVO, HCT116, SW480, SW620) and 102 cases of primary colorectal cancer
      samples were used in this study. Semi-quantitative RT-PCR, methylation specific
      PCR (MSP), Flow cytometry and western blot were employed. Loss of BCL6B
      expression was found in HT29, RKO LOVO, SW480, SW620 and DLD1 cells, and reduced
      expression was found in HCT116 cell line. Complete methylation was found in HT29,
      RKO, LOVO, SW480, SW620 and DLD1 cells, partial methylation was detected in
      HCT116 cells. Restoration of BCL6B expression was induced by 5-Aza treatment in
      these colorectal cancer cells. BCL6B was methylated in 79.4% (81/102) of primary
      human colorectal cancer and reduced expression was associated with promoter
      region hypermethylation (p < 0.05). Methylation of BCL6B is associated with late
      stage (p < 0.05) and lymph node metastasis (p < 0.05). Re-expression of BCL6B
      inhibited cell proliferation, invasion and migration in RKO and HT29 cells. BCL6B
      activated P53 signaling and induced apoptosis, Re-expression of BCL6B sensitized
      RKO and HT29 cells to 5-fluorouracil. In conclusion, BCL6B was frequently
      methylated in human colorectal cancer and its expression was regulated by
      promoter region methylation. Methylation of BCL6B is a prognostic and chemo
      sensitive marker in colorectal cancer. BCL6B suppresses colorectal cancer growth
      by activating P53 signaling. 

PMID- 25973305
TI  - Histone deacetylase 3 inhibits new tumor suppressor gene DTWD1 in gastric cancer.
AB  - Cancer epigenetics plays an important role in the pathogenesis of many cancers
      including gastric cancer. Histone deacetylases (HDACs) emerge as exciting
      therapeutic targets for cancer treatment and prevention. In this study, we
      identified DTWD1 as one of the 122 genes upregulated after treatment of
      trichostatin A (TSA) in two gastric cancer cell lines. Moreover, DTWD1 was
      downregulated in gastric cancer cell lines and primary gastric carcinoma tissues.
      It was further identified as the new target of p53. Then we revealed that HDAC3
      downregulated DTWD1 by disrupting the interaction of p53 with DTWD1 promoter.
      Furthermore, DTWD1 functioned as a tumor suppressor by downregulating cyclin B1
      expression to inhibit proliferation. In summary, as the new p53 target gene,
      DTWD1 was downregulated in gastric cancer by HDAC3 and acted as a novel tumor
      suppressor gene. Specific inhibitors of HDAC3 might be a new approach for gastric
      cancer treatment by activating DTWD1 expression. 

PMID- 25973306
TI  - A specific KRAS codon 13 mutation is an independent predictor for colorectal
      cancer metachronous distant metastases.
AB  - BACKGROUND: In colorectal cancer, there are significant differences between
      synchronous and metachronous distant metastases. However in recent studies,
      synchronous and metachronous metastases were always lumped together, neglecting
      their clinical and molecular differences. The mechanism of the latency of
      metachronous metastases is still unclear. We conducted this study to reveal the
      relationship between EGFR pathways and metachronous metastases, and try to find
      efficient predictors. METHODS: PCRs and pyrosequencing were used to detect KRAS,
      BRAF, PIK3CA and PTEN mutations in primary tumor tissues in a total of 281
      patients from 2002 to 2008. Patients were identified into three groups: no
      metastases group, synchronous-metastases group and metachronous-metastases group.
      Clinical and survival data were collected from a prospective database. RESULTS:
      KRAS codon 13 mutation was an independent predictor only for metachronous distant
      metastases (OR = 11.857, P < 0.001), but not for synchronous metastases. Male
      gender (OR = 2.233, P = 0.024), primary tumor located at rectum (OR = 0.404, P =
      0.041), and primary pN2 stage (OR = 3.361, P = 0.01) were also independent
      predictors for metachronous distant metastases. Different SNPs in KRAS worked
      significantly different in determining synchronous or metachronous metastases.
      BRAF mutation (Univariate, OR = 11.5, P = 0.039) and > 200 ng/ml preoperative CEA
      (Univariate, OR = 41, P = 0.011) potentially predicted metastases within 6 months
      after primary tumor resection. After metachronous metastases, radical resection
      (HR = 0.280, P = 0.002) was the most important protective factor for long-term
      survival. CONCLUSION: There were significant clinical and molecular differences
      between synchronous and metachronous metastases. As an independent predictor,
      KRAS codon 13 mutation might be the key to explain the mechanism of colorectal
      cancer metachronous distant metastases. Together with clinical characteristics,
      it could aid in the early detection of metachronous metastases.

PMID- 25973307
TI  - Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting
      mitochondrial NADH: ubiquinone oxidoreductase (Complex I).
AB  - Isoflavonoids have been shown to inhibit tumor proliferation and metastasis by
      activating cell death pathways. As such, they have been widely studied as
      potential therapies for cancer prevention. The second generation synthetic
      isoflavan analogues ME-143 and ME-344 also exhibit anti-cancer effects, however
      their specific molecular targets have not been completely defined. To identify
      these targets, we examined the effects of ME-143 and ME-344 on cellular
      metabolism and found that they are potent inhibitors of mitochondrial oxidative
      phosphorylation (OXPHOS) complex I (NADH: ubiquinone oxidoreductase) activity. In
      isolated HEK293T mitochondria, ME-143 and ME-344 reduced complex I activity to
      14.3% and 28.6% of control values respectively. In addition to the inhibition of
      complex I, ME-344 also significantly inhibited mitochondrial complex III
      (ubiquinol: ferricytochrome-c oxidoreductase) activity by 10.8%. This inhibition
      of complex I activity (and to a lesser extent complex III activity) was
      associated with a reduction in mitochondrial oxygen consumption. In permeabilized
      HEK293T cells, ME-143 and ME-344 significantly reduced the maximum ADP-stimulated
      respiration rate to 62.3% and 70.0% of control levels respectively in the
      presence of complex I-linked substrates. Conversely, complex II-linked
      respiration was unaffected by either drug. We also observed that the inhibition
      of complex I-linked respiration caused the dissipation of the mitochondrial
      membrane potential (DeltaPsim). Blue native (BN-PAGE) analysis revealed that
      prolonged loss of DeltaPsim results in the destabilization of the native OXPHOS
      complexes. In particular, treatment of 143B osteosarcoma, HeLa and HEK293T human
      embryonic kidney cells with ME-344 for 4 h resulted in reduced steady-state
      levels of mature complex I. Degradation of the complex I subunit NDUFA9, as well
      as the complex IV (ferrocytochrome c: oxygen oxidoreductase) subunit COXIV, was
      also evident. The identification of OXPHOS complex I as a target of ME-143 and ME
      344 advances our understanding of how these drugs induce cell death by disrupting
      mitochondrial metabolism, and will direct future work to maximize the anti-cancer
      capacity of these and other isoflavone-based compounds. 

PMID- 25973308
TI  - Dynamin2 downregulation delays EGFR endocytic trafficking and promotes EGFR
      signaling and invasion in hepatocellular carcinoma.
AB  - Dysregulation of endocytosis was viewed as an emerging feature of cancer
      development and progression. A large GTPase dynamin2 plays a significant role in
      receptor tyrosine kinases (RTKs) endocytosis. The study was designed to
      investigate its roles in hepatocellular carcinoma (HCC) metastasis and its
      underlying mechanism. Dynamin2 expression in cancer tissues from HCC patients was
      assessed by immunohistochemistry and its prognostic significance for the patients
      was conducted using univariate and multivariate analysis. Its role in tumor
      invasion and metastasis was evaluated in vitro by gene silence using siRNA
      mediated approach and the small molecule inhibitor of Dynasore. EGFR expression
      in HCC cell lines and EGFR downstream signaling ERK1/2 was evaluated by Western
      blot and immunofluorescence analyses after Dynamin2 inhibition. Our data
      indicated that low expression of dynamin2 was well correlated with invasion
      characteristics and shorter overall survival. HCC cell migration, colony
      formation and invasion were significantly increased after the inhibition of
      dynamin2 in HCC cells. Internalization of EGFR was markedly reduced when dynamin2
      was knock down or inhibition. In addition, we observed that dynamin2 regulated
      EGF mediated EGFR downstream Ras/ERK1/2 signaling and p-ERK1/2 accumulation in
      nucleus. The results demonstrate a possible mechanism of dynamin involved EGFR
      endocytosis and modulation of metastasis in HCC. Dynamin2 inhibits the invasion
      and metastasis of HCC cells by the promotion of EGFR endocytosis and
      downregulation of ERK1/2 phosphorylation. 

PMID- 25973309
TI  - Reactive oxygen species regulate the differentiation of acute promyelocytic
      leukemia cells through HMGB1-mediated autophagy.
AB  - Acute promyelocytic leukemia (APL) results from a blockade of granulocyte
      differentiation during the promyelocytic stage. As a fusion protein of
      promyelocytic leukemia (PML) and retinoic acid receptor-alpha (RARalpha), PML
      RARalpha oncoprotein is degraded through the differentiation of all-trans
      retinoic acid (ATRA)-induced cells. Here reactive oxygen species (ROS) and high
      mobility group box 1 (HMGB1) were proven essential for the differentiation of APL
      cells. A down-regulation of ROS by ROS quencher (NAC) blocked the differentiation
      of APL cell line NB4 while an over-expression of ROS by superoxide dismutase-1
      (SOD1) RNA interference (RNAi) increased cell differentiation. HMGB1 was vital
      for the differentiation of ROS-mediated NB4 cells and its up-regulation promoted
      ATRA-induced autophagy and the degradation of PML-RARalpha. Furthermore, ATRA
      treatment elevated the levels of ROS, enhanced autophagic flux and thereby
      promoted cytosolic translocation of HMGB1. HMGB1 regulated the interactions
      between ubiquitin-binding adaptor protein p62/SQSTM and PML-RARalpha so as to
      affect the degradation of PML-RARalpha during ATRA-induced autophagy. Also a
      depletion of p62/SQSTM1 expression inhibited HMGB1-mediated PML-RARalpha
      degradation and cell differentiation. The overall results suggested that HMGB1 is
      an essential regulator of ROS-induced cell differentiation. And it may become a
      potential drug target for therapeutic intervention of APL. 

PMID- 25973310
TI  - Profile of differentially expressed intratumoral cytokines to predict the immune
      polarizing side effects of tamoxifen in breast cancer treatment.
AB  - Factors within the tissue of breast cancer (BC) may shift the polarization of
      CD4+ T cells towards Th2 direction. This tendency can promote tumor development
      and be enhanced by the use of tamoxifen during the treatment. Thus, the patients
      with low levels of tumor-induced Th2 polarization prior to tamoxifen treatment
      may better endure the immune-polarizing side effects (IPSE) of tamoxifen and have
      better prognoses. Estimation of Th2 polarization status should help predict the
      IPSE among tamoxifen-treated patients and guide the use of tamoxifen among all BC
      patients before the tamoxifen therapy. Here, we report profiling of
      differentially expressed (DE) intratumoral cytokines as a signature to evaluate
      the IPSE of tamoxifen. The DE genes of intratumoral CD4+ T cells (CD4 DEGs) were
      identified by gene expression profiles of purified CD4+ T cells from BC patients
      and validated by profiling of cultured intratumoral CD4+ T cells. Functional
      enrichment analyses showed a directed Th2 polarization of intratumoral CD4+ T
      cells. To find the factors inducing the Th2 polarization of CD4+ T cells, we
      identified 995 common DE genes of bulk BC tissues (BC DEGs) by integrating five
      independent datasets. Five DE cytokines observed in bulk BC tissues with
      dysregulated receptors in the intratumoral CD4+ T cells were selected as the
      predictor of the IPSE of tamoxifen. The patients predicted to suffer low IPSE
      (low Th2 polarization) had a significantly lower distant relapse risk than the
      patients predicted to suffer high IPSE in independent datasets (n = 608; HR =
      4.326, P = 0.000897; HR = 2.014, P = 0.0173; HR = 2.72, P = 0.04077). Patients
      predicted to suffer low IPSE would benefit from tamoxifen treatment (HR = 2.908,
      P = 0.03905). The DE intratumoral cytokines identified in this study may help
      predict the IPSE of tamoxifen and justify the use of tamoxifen in BC treatment. 

PMID- 25973311
TI  - Semenogelin I promotes prostate cancer cell growth via functioning as an androgen
      receptor coactivator and protecting against zinc cytotoxicity.
AB  - A seminal plasma protein, semenogelin I (SgI), contributes to sperm clotting,
      upon binding to Zn(2+), and can be proteolyzed by prostate-specific antigen
      (PSA), resulting in release of the trapped spermatozoa after ejaculation. In
      contrast, the role of SgI in the development and progression of any types of
      malignancies remains largely unknown. We previously demonstrated that SgI was
      overexpressed in prostate cancer tissues and its expression was enhanced by zinc
      treatment in LNCaP cells. In the current study, using cell lines stably
      expressing SgI, we investigated its biological functions, in conjunction with
      zinc, androgen, and androgen receptor (AR), in prostate cancer. Zinc, without
      SgI, inhibited cell growth of both AR-positive and AR-negative lines. Co
      expression of SgI prevented zinc inhibiting dihydrotestosterone-mediated
      proliferation of AR-positive cells, whereas SgI and/or dihydrotestosterone showed
      marginal effects in AR-negative cells. Similar effects of SgI overexpression in
      LNCaP on dihydrotestosterone-induced cell invasion, such as its significant
      enhancement with zinc, were seen. Overexpression of SgI in LNCaP and CWR22Rv1
      cells also augmented dihydrotestosterone-mediated PSA expression (mRNA, protein)
      in the presence of zinc. However, culture in the conditioned medium containing
      secreted forms of SgI failed to significantly increase cell viability with or
      without zinc. In luciferase reporter gene assays, SgI showed even slight
      inhibitory effects (8% and 15% decreases in PC3 and CWR22Rv1, respectively) at 0
      MUM zinc and significant stimulatory effects (2.1- and 3.2-fold) at 100 MUM zinc
      on dihydrotestosterone-enhanced AR transactivation. Co-immunoprecipitation then
      demonstrated dihydrotestosterone-induced physical interactions between AR and
      SgI. These results suggest that intracellular SgI, together with zinc, functions
      as an AR coactivator and thereby promotes androgen-mediated prostate cancer
      progression. 

PMID- 25973312
TI  - Wnt signaling through Snail1 and Zeb1 regulates bone metastasis in lung cancer.
AB  - Wnt-beta-catenin signaling participates in the epithelial-mesenchymal transition
      (EMT) in a variety of cancers; however, its role in lung cancer induced bone
      metastasis and the underlying mechanisms remain unclear. Here, we demonstrate
      that beta-catenin, Snail1 and Zeb1 were significantly upregulated in bone
      metastasis tissues from human and mouse compared with the normal controls. E
      cadherin expression is negatively regulated by Zeb1, Snail1 and beta-catenin
      during bone metastasis tissues induced by lung cancer. Knocking down Zeb1 and
      Snail1 in lung cancer cell lines showed increased E-cadherin mRNA expression and
      less invasion compared with the original cell lines. In addition, beta-catenin
      knockdown led to the increase of E-cadherin and the decrease of Zeb1 and Snail1,
      which in turn inhibited the invasive properties of lung cancer. Our results
      demonstrated that Wnt signaling through Snail1 and Zeb1 regulates bone metastasis
      in lung cancer. 

PMID- 25973313
TI  - Level of hepatitis B surface antigen might serve as a new marker to predict
      hepatocellular carcinoma recurrence following curative resection in patients with
      low viral load.
AB  - To investigate the association between preoperative HBsAg (hepatitis B surface
      antigen) level and risk of HCC (hepatocellular carcinoma) recurrence following
      curative resection, we enrolled 826 HBV-related HCC patients who underwent
      curative resection and received long-term follow-up at the Eastern Hepatobiliary
      Surgery Hospital (Shanghai, China). Multivariate analyses showed that serum HBsAg
      >= 2000 S/CO, seropositive hepatitis B e antigen (HBeAg), gamma-glutamyl
      transpeptidase > 61 U/L, prothrombin time > 13 s, multinodularity, lager tumor
      size, and major portal vein invasion were independently associated with a
      increased risk of HCC recurrence. Compared with HCC patients with HBsAg level <
      2000 S/CO, HCC patients with HBsAg level >= 2000 S/CO had a higher prevalence of
      seropositive HBeAg, antiviral therapy, and cirrhosis; were younger; and had a
      higher levels of alanine transaminase (ALT), aspartate aminotransferase (AST),
      and HBV viral load. Multivariable stratified analyses showed HCC patients with
      HBsAg level < 2000 S/CO tended to have a lower incidence of HCC recurrence in
      following subgroups of patients, including for noncirrhotic (HR, 0.561; 95% CI,
      0.345-0.914), HBV DNA < 2000 IU/mL (HR, 0.604; 95% CI, 0.401-0.912), ALT <= 41
      U/L (HR, 0.643; 95% CI, 0.440-0.942), AST <= 37 U/L (HR, 0.672; 95% CI, 0.459
      0.983), and seronegative HBeAg (HR, 0.682; 95% CI, 0.486-0.958). When we
      evaluated HBeAg-negative patients with HBV DNA < 2000 IU/mL, HBsAg level still
      determined risk of HCC recurrence (p = 0.014), but not HBV DNA (p = 0.550) and
      ALT (p = 0.186). These results suggest high levels of HBsAg increase risk of HCC
      recurrence following curative resection. HBsAg level might serve as a new marker
      to complement HBV DNA level in predicting HCC recurrence, especially in HBeAg
      negative patients with low viral load. 

PMID- 25973314
TI  - TEM7 (PLXDC1), a key prognostic predictor for resectable gastric cancer, promotes
      cancer cell migration and invasion.
AB  - Tumor endothelial marker 7 (TEM7) is a new candidate of molecular target for
      antiangiogenic therapy. This study aims to evaluate its expression in gastric
      cancer (GC) and to explore the correlation between its expression and the
      clinical outcome of patients. Expression of TEM7 was analyzed in both tumor
      tissues and cell lines of GC by real-time quantitative RT-PCR (qRT-PCR) and
      Western blot. RNA interference (RNAi) approaches were used to investigate the
      biological functions of TEM7. The effects of TEM7 on cell migration and invasion
      were evaluated by Transwell assays. In vitro experiments revealed that TEM7 was
      significantly overexpressed in GC cell lines (N87, AGS and SGC-7901) by 2-fold to
      4-fold, and knockdown of TEM7 could significantly inhibit cancer cell migration
      and invasion. For GC patients, TEM7 gene expression was elevated in tumors in
      most cases (25/31), and its expression was closely correlated with tumor
      differentiation, depth of cancer invasion, lymphatic metastasis and TNM stage.
      The overall survival of TEM7 (-) group was significantly higher than that of TEM7
      (+) group (P = 0.048) and TEM7 (++) group (P = 0.003). TEM7 is highly expressed
      in GC and is likely correlated with tumor invasion and migration, and thus its
      expression is closely related to the clinical outcome of patients. 

PMID- 25973315
TI  - Tenascin-C expression is associated with poor prognosis in hepatocellular
      carcinoma (HCC) patients and the inflammatory cytokine TNF-alpha-induced TNC
      expression promotes migration in HCC cells.
AB  - Although tenascin-c (TNC) in inflammatory microenvironment contributes to
      progression in some tumors, its role in hepatocellular carcinoma (HCC) in
      metastasis and the mechanism by which TNC expression is regulated in HCC cells
      are elusive. In this study, we examined TNC expression in 100 HCC tissue samples
      by immunohistochemistry and compared which between the groups with or without
      metastasis. TNC expression was higher in metastatic HCC tissues than that in the
      non-metastatic HCC tissues, which was associated with the Knodell inflammation
      scores. Importantly, high level of TNC expression was associated with lower
      survival rate and shorter survival time in the HCC patients. We then investigated
      the mechanism by which TNC expression is regulated in HCC cells with an in vitro
      cell culture system. The recombinant TNF-alpha and conditioned medium from
      macrophages induced TNC expression at both mRNA and protein levels in HepG2
      cells. The induction of TNC expression by conditioned medium from macrophages was
      suppressed by a TNF-alpha neutralizing antibody. TNF-alpha-promoted cell
      migration was inhibited by a TNC siRNA. In addition, TNF-alpha-induced TNC
      expression was blocked by a NF-kappaB pathway inhibitor. These results suggest
      that TNF-alpha in the tumor microenvironment induces TNC expression in HCC cells
      through the NF-kappaB pathway, which in turn, promotes HCC cell migration. Thus,
      TNC may play an important role in promoting HCC metastasis and TNC expression
      could be a predictive factor for poor prognosis in HCC patients. 

PMID- 25973316
TI  - Tumor-specifically hypoxia-induced therapy of SPRY1/2 displayed differential
      therapeutic efficacy for melanoma.
AB  - Activation of receptor tyrosine kinase (RTK) signalling pathways is frequently
      correlated to cancer cell proliferation, angiogenesis and cell survival. Sprouty
      (SPRY) proteins function as a physiological endogenous inhibitor of RTK
      signalling pathways, have been shown to be deregulated in most cancer cells.
      Here, we demonstrated that over-expression of SPRY1 and SPRY2 inhibited B16F10
      cell proliferation through G1 phase arrest in vitro, and SPRY2 showed more potent
      inhibitory effects than SPRY1. In order to tumor-specific delivery of SPRY1/2 in
      vivo, two strains of attenuated Salmonella typhimurium VNP20009 (VNP-PQE-SPRY1
      and VNP-PQE-SPRY2) were constructed to specifically express SPRY1 or SPRY2 under
      the control of a hypoxia-induced nirB promoter. The efficiency and specificity of
      the recombinant strains were validated in both bacteria and animal tumor models.
      SPRY1 and SPRY2 gene could be specifically driven by the nirB promoter under
      hypoxia, but not normoxia conditions. In addition, the tumor-targeting ability of
      VNP-PQE-SPRY1 or VNP-PQE-SPRY2 was similar with VNP. VNP-PQE-SPRY2 significantly
      suppressed melanoma growth in vivo, suggesting that SPRY2 is a more efficient
      agent for melanoma therapy. Moreover, the antitumor effect of VNP-SPRY2 is mainly
      mediated through the inhibition of ERK1/2 phosphorylation, which leads to the
      inhibition of proliferation in melanoma. Taken together, our results indicated
      that SPRY2 displayed more potent melanoma suppression than SPRY1 both in vitro
      and in vivo, and the hypoxia-induced tumor-specific gene therapy of SPRY2
      delivered by VNP20009 is a promising strategy for melanoma therapy. 

PMID- 25973317
TI  - The microRNA-520a-3p inhibits proliferation, apoptosis and metastasis by
      targeting MAP3K2 in non-small cell lung cancer.
AB  - Growing evidence indicates that miR-520a was involved in the complement attack
      and migration of tumor cells, but nonetheless, the role of miR-520a-3p in non
      small cell lung cancer (NSCLC) is not clear. Mitogen-activated protein kinase
      kinase kinase 2 (MAP3K2) is a kinase belonging to the serine/threonine protein
      kinase family. To develop potential therapy targeting MAP3K2, we studied the
      roles of miR-520a-3p in the proliferation, apoptosis and metastasis of NSCLC. The
      expression levels of miR-520a-3p were quantified in tumor tissues of NSCLC by qRT
      PCR, and the mimics and inhibitors were used to verify the function of miR-520a
      3p. The cell proliferation was evaluated by MTT assay, and the migration and
      invasion was evaluated by transwell assay. The athymic mice subcutaneous
      injection was used to research NSCLC cell tumor formation. The bioinformatics
      tools and luciferase assay was applied to detect the relationship between miR
      520a-3p and its target. Protein levels of miR-520a-3p target was determined by
      western blot analysis. MiR-520a-3p expression was decreased in the NSCLC tissues
      compared with their normal counterparts and lower expression of miR-520a-3p in
      NSCLC tissues was associated with a higher clinical stage, NSCLC metastasis and
      poor prognosis. Inhibition of expression of miR-520a-3p can reduce in vitro NSCLC
      cell migration and invasion as well as in vivo metastasis. MAP3K2 mRNA contains a
      binding site for miR-520a-3p in the 3'UTR. MAP3K2 is one of target of miR-520a
      3p. Together, our data demonstrated that miR-520a-3p inhibits proliferation,
      apoptosis and metastasis in NSCLC by targeting MAP3K2, and miR-520a-3p may be
      used as a prognosis marker for NSCLC in clinical research. 

PMID- 25973318
TI  - DCA promotes progression of neuroblastoma tumors in nude mice.
AB  - Even in the presence of oxygen most cancer cells convert glucose to lactate via
      pyruvate instead of performing oxidative phosphorylation (aerobic glycolysis
      Warburg effect). Thus, it has been considered to shift pyruvate - the metabolite
      of aerobic glycolysis - to acetylCoA by activation of pyruvate dehydrogenase
      (PDH). AcetylCoA will then be metabolized by oxidative phosphorylation.
      Therefore, the purpose of this study was to shift tumor cells from aerobic
      glycolysis to oxidative phosphorylation using dichloroacetate (DCA), an inhibitor
      of PDH-kinase. The effects of DCA were assayed in vitro in Neuro-2a (murine
      neuroblastoma), Kelly and SK-N-SH (human neuroblastoma) as well as SkBr3 (human
      breast carcinoma) cell lines. The effects of DCA on tumor development were
      investigated in vivo using NMRI nu/nu mice bearing subcutaneous Neuro-2a
      xenografts. For that purpose animals were treated continuously with DCA in the
      drinking water. Tumor volumes were monitored using caliper measurements and via
      [18F]-FDG-positron emission tomography. DCA treatment increased
      viability/proliferation in Neuro-2a and SkBr3 cells, but did not cause
      significant alterations of PDH activity. However, no significant effects of DCA
      could be observed in Kelly and SK-N-SH cells. Accordingly, in mice bearing Neuro
      2a xenografts, DCA significantly increased tumor proliferation compared to mock
      treated mice. Thus, we could demonstrate that DCA - an indicated inhibitor of
      tumor growth - efficiently promotes tumor growth in Neuro-2a cells in vitro and
      in vivo. 

PMID- 25973319
TI  - Hemolysis-free plasma miR-214 as novel biomarker of gastric cancer and is
      correlated with distant metastasis.
AB  - Circulating miRNAs gains popularity for its potential ability to serve as
      biomarkers of cancer. The aim of present study was to evaluate the usefulness of
      plasma miR-214 as novel biomarkers for gastric cancer (GC) detection. Attempts
      were made to address several pitfalls in sample processing and study design in
      previous studies. We conducted a two-step analysis: (1) in pilot study comprising
      of 30 patients and 30 controls, levels of miR-214 were significantly higher in
      primary GC tissues than normal tissues (P = 0.0215). Plasma miR-214 was
      significantly higher in patients with GC than in controls (P < 0.0001). (2) In
      test of larger cohort, there was significantly decreasing tendency of plasma miR
      214 from patients before, 14 days and 1 month after surgical resection (P <
      0.0001). There were significantly higher levels of miR-214 in 80 GC patients than
      in 70 controls (P < 0.0001). Receiver operating characteristics (ROC) curves
      yielded area under the curve (AUC) value of 0.845. Moreover, high plasma miR-214
      had significant correlation with distant metastasis (P = 0.038). Thus, our data
      suggest that plasma miR-214 was novel hemolysis-free markers of gastric cancer. 

PMID- 25973320
TI  - Membranous expressions of Lewis y and CAM-DR-related markers are independent
      factors of chemotherapy resistance and poor prognosis in epithelial ovarian
      cancer.
AB  - BACKGROUND: Chemotherapy resistance is a common problem faced by patients
      diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific
      or sensitive clinical biomarkers that maybe implemented to identify chemotherapy
      resistance and give insight to prognosis. The aim of this study is to investigate
      the roles of Lewis y antigen and the markers associated with cell-adhesion
      mediated drug resistance (CAM-DR) in patients with EOC. METHODS: 92 EOC patients
      who were treated with systemic chemotherapy after cytoreductive surgery were
      included in this analysis. Patients were divided into two groups, chemotherapy
      sensitive (n = 56) and resistant (n = 36). Immunohistochemical (IHC) staining for
      Lewis y and CAM-DR-related cell surface proteins including CD44, CD147, HE4
      (Human epididymis protein 4), integrin alpha5, beta1, alphav and beta3 were
      conducted on tissues collected during primary debulking surgery. Using
      multivariate logistic regressions, IHC results were compared to clinical
      variables and chemotherapy resistance to determine possible correlations. The
      relationships between IHC expression and progression-free survival (PFS) and
      overall survival (OS) were analyzed using Kaplan-Meier method and Cox regression
      analysis. RESULTS: Membranous expression of Lewis y and all these CAM-DR-related
      markers were significantly higher in the resistant group than that of the
      sensitive group (all P < 0.01). Multivariate regression analysis revealed that
      high expression of Lewis y, CD44, HE4, integrin alpha5 and beta1 as well as
      advanced FIGO stage were independent risk factors for chemotherapy resistance
      (all P < 0.05). Advanced FIGO stage, lymph node metastasis and high expression of
      Lewis y, CD44, CD147, HE4, integrin alpha5, beta1 were associated with a shorter
      PFS and OS (all P < 0.05). Moreover, multivariate COX analysis demonstrated that
      the following variates were independent predictors of worse PFS and OS survival:
      late FIGO stage (P = 0.013, 0.049), high expressions of Lewis y (P = 0.010,
      0.036), HE4 (P = 0.006, 0.013) and integrin beta1 (PFS, P = 0.003), integrin
      alpha5 (OS, P = 0.019). CONCLUSION: Membranous expression of Lewis y and CAM-DR
      related markers including CD44, CD147, HE4, integrin alpha5, beta1, alphav and
      beta3 are associated with the development of chemotherapy resistance. High
      expression of Lewis y antigen and CAM-DR-related markers including CD44, CD147,
      HE4, integrin alpha5 and beta1 are independent markers for PFS and OS, in which
      Lewis y and HE4 are the most significant.

PMID- 25973321
TI  - Number of negative lymph nodes should be considered for incorporation into
      staging for breast cancer.
AB  - This study aimed to investigate the prognostic value of the number of involved
      lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR),
      number of negative lymph nodes (NLNs), and log odds of positive lymph nodes
      (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients
      who received a mastectomy or breast-conserving surgery were retrospectively
      reviewed. The log-rank test was used to compare survival curves, and Cox
      regression analysis was performed to identify prognostic factors. The median
      follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and
      overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis
      showed that pN stage, LNR, number of RLNs, and number of NLNs were significant
      prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant
      prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN
      stage and the number of NLNs were independent prognostic factors for DFS and OS.
      A higher number of NLNs was associated with higher DFS and OS, and a higher
      number of involved lymph nodes were associated with poorer DFS and OS. Patients
      with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed
      that the NLNs count had a prognostic value in patients with different pT stages
      and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage
      and NLNs count have a better prognostic value compared to the RLNs count, LNR,
      and LODDS. Number of negative lymph nodes should be considered for incorporation
      into staging for breast cancer. 

PMID- 25973323
TI  - Opioid abuse and overdose crisis: new treatment available-controversy continues
      between harm-reduction treatment and abstinence treatment.

PMID- 25973322
TI  - Radiotherapy in muscle-invasive bladder cancer: the latest research progress and
      clinical application.
AB  - The role of radiotherapy (RT) in the management of urinary bladder cancer has
      undergone several alterations along the last decades. Recently, many protocols
      have been developed supporting the use of multi-modality therapy, and the concept
      of organ preservation began to be reconsidered. Advances in radiotherapy
      planning, verification, and delivery provide a method to optimize radiotherapy
      for bladder cancer and overcome difficulties which have previously limited the
      success of this treatment. They offer the opportunity to enhance the therapeutic
      ratio by reducing the volume of normal tissue irradiated and by increasing
      radiation dose or using more intensive fractionation and synchronous chemotherapy
      regimes. These techniques have a large potential to improve the therapeutic
      outcome of bladder cancer. In the near future, it should be possible to offer
      selected patients with muscle-invasive bladder cancer an organ-sparing, yet
      effective combined-modality treatment. In this review, we aim to present the role
      of radiotherapy in the management of muscle invasive bladder cancer. Alternative
      methods of improving treatment accuracy such as helical tomotherapy, adaptive
      radiotherapy and radiochemotherapy are also discussed. 

PMID- 25973324
TI  - Buprenorphine treatment for narcotic addiction: not without risks.
AB  - While most clinicians will never prescribe buprenorphine or combined
      buprenorphine/naloxone, familiarity with the risks of these pharmacological
      approaches to the treatment of narcotic addiction remains relevant. Overall,
      medication-assisted treatment has clearly resulted in meaningful gains for a
      number of individuals who are addicted to narcotics (i.e., opiates and opioids).
      However, a certain level of risk is inherent with these approaches. For example,
      both buprenorphine and buprenorphine/naloxone may be diverted and misused (e.g.,
      intravenously injected, intranasally administered), particularly buprenorphine.
      Likewise, when illicitly injected, both can cause infectious complications as
      well as result in death from overdose. The risk of death with buprenorphine
      overdose appears to be heightened with the coadministration of either
      benzodiazepines or sedative/hypnotics. To conclude, as with all interventions in
      medicine, buprenorphine treatment for narcotic addiction has a clinically
      fluctuating risk/benefit equation that must be continually monitored. 

PMID- 25973325
TI  - Avoiding risk with nonadherent patients.

PMID- 25973326
TI  - Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in
      veterinary medicine.
AB  - Adipose tissue derived stem cells (ASCs) are mesenchymal stem cells which can be
      obtained from different adipose tissue sources within the body. It is an abundant
      cell pool, which is easy accessible and the cells can be obtained in large
      numbers, cultivated and expanded in vitro and prepared for tissue engineering
      approaches, especially for skeletal tissue repair. In the recent years this cell
      population has attracted a great amount of attention among researchers in human
      as well as in veterinary medicine. In the meantime ASCs have been well
      characterized and their use in regenerative medicine is very well established.
      This review focuses on the characterization of ASCs for their use for tissue
      engineering approaches especially in veterinary medicine and also highlights a
      selection of clinical trials on the basis of ASCs as the relevant cell source. 

PMID- 25973327
TI  - Transdifferentiation of endothelial cells to smooth muscle cells play an
      important role in vascular remodelling.
AB  - Pulmonary artery remodelling it is a major feature of pulmonary hypertension
      (PH). It is characterised by cellular and structural changes of the pulmonary
      arteries causing higher pulmonar vascular resistance and right ventricular
      failure. Abnormal deposition of smooth muscle-like (SM-like) cells in normally
      non-muscular, small diameter vessels and a deregulated control of endothelial
      cells are considered pathological features of PH. The origin of the SM-like cells
      and the mechanisms underlying the development and progression of this remodelling
      process are not understood. Endothelial cells within the intima may migrate from
      their organised layer of cells and transition to mesenchymal or SM-like phenotype
      in a process called endothelial-mesenchymal transition (EnMT). Traditionally,
      Waddington's epigenetic landscape illustrates that fates of somatic cells are
      progressively determined to compulsorily follow a downhill differentiation
      pathway. EnMT induces the transformation of cells with stem cell traits,
      therefore contrasting Waddington's theory and confirming that cell fate seems to
      be far more flexible than previously thought. The prospect of therapeutic
      inhibition of EnMT to delay or prevent PH may represent a promising new treatment
      modality. 

PMID- 25973328
TI  - Stem cells for the cell and molecular therapy of type 1 diabetes mellitus (T1D):
      the gap between dream and reality.
AB  - In spite of intense research, over the past 2-3 decades, targeted to validating
      methods for the cure of T1D, based on cell substitution therapy in the place of
      exogenously administered insulin injections, achievement of the final goal
      continues to remain out of reach. In fact, aside of very limited clinical success
      of the few clinical trials of pancreatic islet cell transplantation in totally
      immunosuppressed patients with T1D, the vast majority of these diabetic patients
      invariably is insulin-dependent. New advances for cell and molecular therapy for
      T1D, including use of stem cells, are reviewed and discussed in an attempt to
      clearly establish where we are and where are we may go for the final cure for
      T1DM. 

PMID- 25973329
TI  - Experimental approaches to derive CD34+ progenitors from human and nonhuman
      primate embryonic stem cells.
AB  - Traditionally, CD34 positive cells are predominantly found in the umbilical cord
      and bone marrow, thus are considered as hematopoietic progenitors. Increasing
      evidence has suggested that the CD34+ cells represent a distinct subset of cells
      with enhanced progenitor activity; CD34 is a general marker of progenitor cells
      in a variety of cell types. Because the CD34 protein shows expression early on in
      hematopoietic and vascular-associated tissues, CD34+ cells have enormous
      potential as cellular agents for research and for clinical cell transplantation.
      Directed differentiation of embryonic stem cells will give rise to an
      inexhaustible supply of CD34+ cells, creating an exciting approach for biomedical
      research and for regenerative medicine. Here, we review the main methods that
      have been published for the derivation of CD34+ cells from embryonic stem cells;
      specifically those approaches the human and nonhuman primate stem cells. We
      summarize current status of this field, compare the methods used, and evaluate
      the issues in translating the bench science to bedside therapy. 

PMID- 25973330
TI  - An effective freezing/thawing method for human pluripotent stem cells cultured in
      chemically-defined and feeder-free conditions.
AB  - Culturing human Pluripotent Stem Cells (hPSC)s in chemically defined medium and
      feeder-free condition can facilitate metabolome and proteome analysis of
      culturing cells and medium, and reduce regulatory concerns for clinical
      application of cells. And in addition, if hPSC are passaged and cryopreserved in
      single cells it also facilitates quality control of cells at single cell level.
      Here we report a robust single cell freezing and thawing method of hPSCs cultured
      in chemically-defined medium TeSR(TM)-E8(TM) and on cost-effective recombinant
      human Vitronectin-N (rhVTN-N)-coated dish. Cells are dissociated into single
      cells with recombinant TrypLE(TM) Select and 0.5 mM EDTA/PBS (3:1 solution) in
      the presence of Rock inhibitor and cryopreserved with chemically defined
      CryoStem(TM). Approximately 60% of cells were viable after dissociation.
      Aggrewell(TM) 400 was used to form cell clumps of 500 cells after thaw in the
      presence of Rock inhibitor and cells were cultured for two days with TeSR-E8.
      Cells clumps were then seeded on rhVTN-N-coated dish and cultured with TeSR-E8
      for two days prior to the first passage after thawing. Number of viable cells at
      the first passage increased around 10 times of that just before freezing. This
      robust single cell freezing method for hPSCs cultured in chemically defined
      medium will facilitate quality control of cultured cells at single cell level
      before cryopreservation and consequently assure the quality of cells in frozen
      vials for further manipulation after thawing. 

PMID- 25973331
TI  - The effect of autologous bone marrow mononuclear cell transplantation on the
      survival duration in Amyotrophic Lateral Sclerosis - a retrospective controlled
      study.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative
      disorder with fatal prognosis. Cellular therapy has been studied for ALS in
      various animal models and these advances have highlighted its potential to be a
      treatment modality. This is a retrospective controlled cohort study of total 57
      patients. Out of these, 37 patients underwent autologous bone marrow mononuclear
      cell transplantation in addition to standard rehabilitation and Riluzole. Control
      group consisted of 20 patients who did not receive cell transplantation. The
      survival duration since the onset of the disease for both the groups was computed
      using a Kaplan-Meier Survival analysis and compared using log-rank test. Effect
      of age at onset, type of onset and lithium on survival duration in the
      intervention group was analyzed. Mean survival duration of patients in
      intervention group was 87.76 months which was higher than the control group mean
      survival duration of 57.38 months. Survival duration was significantly (p =
      0.039) higher in people with the onset of the disease below 50 years of age. Limb
      onset and lithium also showed positive influence on the survival duration. Mean
      survival duration of the intervention group was also higher than the survival
      duration of ALS patients in previous epidemiological studies. In addition to the
      standard treatment with Riluzole, early intervention with combination of BMMNCs
      transplantation and Lithium may have a positive effect on the survival duration
      in ALS. Prospective randomized controlled studies with a larger sample size and
      rigorous methodology are required for conclusive findings. 

PMID- 25973332
TI  - Imaging of prostate cancer with PET/CT using (18)F-Fluorocholine.
AB  - While (18)F-Fluorodeoxyglucose ((18)F-FDG) Positron-Emission Tomography (PET) has
      limited value in prostate cancer (PCa), it may be useful for specific subgroups
      of PCa patients with hormone-resistant poorly differentiated cell types. (18)F
      Fluorocholine ((18)F-FCH) PET/CT has been increasingly used in primary and
      recurrent PCa and has been shown to add valuable information. Although there is a
      correlation between the foci of activity and the areas of malignancy in the
      prostate gland, the clinical value of (18)F-FCH is still controversial for
      detection of the malignant focus in the prostate. For the T-staging of PCa at
      diagnosis the value of (18)F-FCH is limited. This is probably due to limited
      resolution of PET system and positive findings in benign prostate diseases.
      Conversely, (18)F-FCH PET/CT is a promising imaging modality for the delineation
      of local and distant nodal recurrence and bone metastases and is poised to have
      an impact on therapy management. In this review, recent studies of (18)F-FCH
      PET/CT in PCa are summarized. 

PMID- 25973333
TI  - Dosimetry of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 - impact on the feasibility of
      insulinoma internal radiotherapy.
AB  - [(68)Ga]-DO3A-VS-Cys(40)-Exendin-4 has been shown to be a promising imaging
      candidate for targeting glucagon like peptide-1 receptor (GLP-1R). In the light
      of radiotheranostics and personalized medicine the (177)Lu-labelled analogue is
      of paramount interest. In this study we have investigated the organ distribution
      of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 in rat and calculated human dosimetry
      parameters in order to estimate the maximal acceptable administered
      radioactivity, and thus potential applicability of [(177)Lu]-DO3A-VS-Cys(40)
      Exendin-4 for internal radiotherapy of insulinomas. Nine male and nine female
      Lewis rats were injected with [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 for ex vivo
      organ distribution study at nine time points. The estimation of human organ/total
      body absorbed and total effective doses was performed using Organ Level Internal
      Dose Assessment Code software (OLINDA/EXM 1.1). Six more rats (male: n = 3;
      female: n = 3) were scanned by single photon emission tomography and computed
      tomography (SPECT-CT). The renal function and potential cell dysfunction were
      monitored by creatinine ISTAT and glucose levels. The fine uptake structure of
      kidney and pancreas was investigated by ex vivo autoradiography. Blood clearance
      and washout from most of the organs was fast. The kidney was the dose-limiting
      organ with absorbed dose of 5.88 and 6.04 mGy/MBq, respectively for female and
      male. Pancreatic beta cells demonstrated radioactivity accumulation. Renal
      function and beta cell function remained unaffected by radiation. The absorbed
      dose of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 to kidneys may limit the clinical
      application of the agent. However, hypothetically, kidney protection and
      peptidase inhibition may allow reduction of kidney absorbed dose and
      amplification of tumour absorbed doses. 

PMID- 25973334
TI  - Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung
      cancer patients planned for radiotherapy: a dynamic PET/CT study.
AB  - Aim of this study was to evaluate and compare, by means of dynamic and static
      PET/CT, the distribution patterns and pharmacokinetics of fluorine-18
      fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F
      FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity
      modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable
      stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor
      metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was
      based on visual analysis, semi-quantitative (SUV) calculations and absolute
      quantitative estimations, after application of a two-tissue compartment model and
      a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung
      tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in
      total 43 (18)F-FDG avid metastases; these patients were excluded from
      radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint
      tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4,
      SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were
      SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02,
      influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The
      respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26,
      k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically
      significant correlation was observed between the two tracers. (18)F-FDG PET/CT
      changed therapy management in six patients, by excluding them from planned IMRT.
      (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority
      of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers'
      kinetics indicates that they reflect different molecular mechanisms and implies
      the discordance between increased glycolysis and hypoxia in the malignancy. 

PMID- 25973335
TI  - Evaluation of tumor ischemia in response to an indole-based vascular disrupting
      agent using BLI and (19)F MRI.
AB  - Vascular disrupting agents (VDAs) have been proposed as an effective broad
      spectrum approach to cancer therapy, by inducing ischemia leading to hypoxia and
      cell death. A novel VDA (OXi8007) was recently reported to show rapid acute
      selective shutdown of tumor vasculature based on color-Doppler ultrasound. We
      have now expanded investigations to noninvasively assess perfusion and
      hypoxiation of orthotopic human MDA-MB-231/luc breast tumor xenografts following
      the administration of OXi8007 based on dynamic bioluminescence imaging (BLI) and
      magnetic resonance imaging (MRI). BLI showed significantly lower signal four
      hours after the administration of OXi8007, which was very similar to the response
      to combretastatin A-4P (CA4P), but the effect lasted considerably longer, with
      the BLI signal remaining depressed at 72 hrs. Meanwhile, control tumors exhibited
      minimal change. Oximetry used (19)F MRI of the reporter molecule
      hexafluorobenzene and FREDOM (Fluorocarbon Relaxometry using Echo Planar Imaging
      for Dynamic Oxygen Mapping) to assess pO2 distributions during air and oxygen
      breathing. pO2 decreased significantly upon the administration of OXi8007 during
      oxygen breathing (from 122 +/- 64 to 34 +/- 20 Torr), with further decrease upon
      switching the gas to air (pO2 = 17 +/- 9 Torr). pO2 maps indicated intra-tumor
      heterogeneity in response to OXi8007, though ultimately all tumor regions became
      hypoxic. Both BLI and FREDOM showed the efficacy of OXi8007. The pO2 changes
      measured by FREDOM may be crucial for future study of combined therapy. 

PMID- 25973336
TI  - Imaging modality utilization trends in patients with stage III-IV oropharyngeal
      squamous cell carcinoma.
AB  - The objective of this study is to establish the utilization trends of CT, MRI,
      and FDG-PET/CT for evaluation of oropharyngeal squamous cell carcinoma (OPSCC)
      patients. A total of 173 patients with newly diagnosed stage III or IV OPSCC
      between 2003 and 2009 were included. Frequency of imaging modality use, divided
      into four time periods (2003-04, 2005-06, 2007-08 and 2009), was evaluated. For
      initial staging, percentage of PET/CT use was 64.6%, 87.5%, 94.1% and 96.3%, with
      an increasing trend (p < 0.001). The CT (p = 0.762) and MRI (p = 0.224) use
      demonstrated no change in trend. For post-treatment imaging, percentage of PET/CT
      use was 59.5%, 68.6%, 89.7% and 100%, with an increasing trend (p < 0.001). The
      CT use demonstrated a decreasing trend (p = 0.004) and MRI showed no trend change
      (p = 0.231). PET/CT is used with an increasing trend for initial staging and has
      become a central imaging modality for follow up evaluation after treatment, for
      advanced OPSCC. 

PMID- 25973337
TI  - Differentiation of metastatic vs degenerative joint disease using semi
      quantitative analysis with (18)F-NaF PET/CT in castrate resistant prostate cancer
      patients.
AB  - Fluorine 18 Sodium Fluoride ((18)F-NaF) (sodium fluoride) PET/CT is a highly
      sensitive but is a non-specific method for identifying bone metastases.
      Qualitative scan interpretation using low dose CT for lesion localization is
      often complicated by the presence of co-existing degenerative joint disease
      (DJD). A semi-quantitative analysis might help in accurately differentiating
      benign from metastatic osseous lesions. The aim of the study was to evaluate the
      clinical utility of (18)F-NaF PET/CT in differentiating DJD from metastatic
      disease in the skeleton using a qualitative analysis as well as a semi
      quantitative approach using the SUVmax and to determine if there is an upper
      limit of SUVmax value that can reliably differentiate metastases from DJD.
      Baseline (18)F-NaF PET/CT scans were performed for 17 castrate resistant prostate
      cancer patients (CRPC). A qualitative as well as semi-quantitative analysis using
      maximum standardized uptake value (SUVmax) based on body weight was performed for
      65 metastatic and 56 DJD sites identified on the low dose CT scan acquired as a
      part of whole body PET/CT scan. The SUVmax range in DJD was 2.6-49.9 (mean: 6.2).
      The SUVmax range for metastatic lesions was 11.2-188 (mean: 160). The SUVmax
      value for metastatic as well as areas of DJD showed significant variation during
      treatment. Bone metastases showed statistically significantly higher SUVmax than
      DJD using a mixed effect regression model. ROC/AUC analysis was performed based
      on averaging the SUVs over all lesions in each subject. The AUC was found to be
      fairly high at 0.964 (95% CI: 0.75-0.996). The SUVmax over 50 always represented
      a bone metastasis and below 12 always represented a site of DJD. The results of
      our preliminary data show that semi-quantitative analysis is complementary to the
      qualitative analysis in accurately identifying DJD from metastatic disease. The
      cut-off SUVmax of 50 can help in differentiating DJD from bone metastases. 

PMID- 25973338
TI  - Comparison of autologous (111)In-leukocytes, (18)F-FDG, (11)C-methionine, (11)C
      PK11195 and (68)Ga-citrate for diagnostic nuclear imaging in a juvenile porcine
      haematogenous staphylococcus aureus osteomyelitis model.
AB  - The aim of this study was to compare (111)In-labeled leukocyte single-photon
      emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG)
      positron emission tomography (PET) to PET with tracers that potentially could
      improve detection of osteomyelitis. We chose (11)C-methionine, (11)C-PK11195 and
      (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous
      osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven
      days after intra-arterial inoculation in the right femoral artery with a porcine
      strain of Staphylococcus aureus using a sequential scan protocol with (18)F-FDG,
      (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In
      labelled autologous leukocytes. This was followed by necropsy of the pigs and
      gross pathology, histopathology and microbial examination. The pigs developed a
      total of five osteomyelitis lesions, five lesions characterized as
      abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes.
      None of the tracers accumulated in joints with arthritis. By comparing the 10
      infectious lesions, (18)F-FDG accumulated in nine, (111)In-leukocytes in eight,
      (11)C-methionine in six, (68)Ga-citrate in four and (11)C-PK11195 accumulated in
      only one lesion. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT
      in marking infectious and proliferative, i.e. hyperplastic, lesions. However,
      leukocyte SPECT was performed as early scans, approximately 6 h after injection
      of the leukocytes, to match the requirements of the 18 h long scan protocol.
      (11)C-methionine and possibly (68)Ga-citrate may be useful for diagnosis of soft
      issue lesions. 

PMID- 25973339
TI  - Added value of cost-utility analysis in simple diagnostic studies of accuracy:
      (18)F-fluoromethylcholine PET/CT in prostate cancer staging.
AB  - Diagnostic studies of accuracy targeting sensitivity and specificity are commonly
      done in a paired design in which all modalities are applied in each patient,
      whereas cost-effectiveness and cost-utility analyses are usually assessed either
      directly alongside to or indirectly by means of stochastic modeling based on
      larger randomized controlled trials (RCTs). However the conduct of RCTs is
      hampered in an environment such as ours, in which technology is rapidly evolving.
      As such, there is a relatively limited number of RCTs. Therefore, we investigated
      as to which extent paired diagnostic studies of accuracy can be also used to shed
      light on economic implications when considering a new diagnostic test. We propose
      a simple decision tree model-based cost-utility analysis of a diagnostic test
      when compared to the current standard procedure and exemplify this approach with
      published data from lymph node staging of prostate cancer. Average procedure
      costs were taken from the Danish Diagnosis Related Groups Tariff in 2013 and life
      expectancy was estimated for an ideal 60 year old patient based on prostate
      cancer stage and prostatectomy or radiation and chemotherapy. Quality-adjusted
      life-years (QALYs) were deduced from the literature, and an incremental cost
      effectiveness ratio (ICER) was used to compare lymph node dissection with
      respective histopathological examination (reference standard) and (18)F
      fluoromethylcholine positron emission tomography/computed tomography (FCH
      PET/CT). Lower bounds of sensitivity and specificity of FCH-PET/CT were
      established at which the replacement of the reference standard by FCH-PET/CT
      comes with a trade-off between worse effectiveness and lower costs. Compared to
      the reference standard in a diagnostic accuracy study, any imperfections in
      accuracy of a diagnostic test imply that replacing the reference standard
      generates a loss in effectiveness and utility. We conclude that diagnostic
      studies of accuracy can be put to a more extensive use, over and above a mere
      indication of sensitivity and specificity of an imaging test, and that health
      economic considerations should be undertaken when planning a prospective
      diagnostic accuracy study. These endeavors will prove especially fruitful when
      comparing several imaging techniques with one another, or the same imaging
      technique using different tracers, with an independent reference standard for the
      evaluation of results. 

PMID- 25973340
TI  - Effect of reconstruction algorithms on the accuracy of (99m)Tc sestamibi SPECT/CT
      parathyroid imaging.
AB  - The superiority of SPECT/CT over SPECT for (99m)Tc-sestamibi parathyroid imaging
      often is assumed to be due to improved lesion localization provided by the
      anatomic component (computed tomography) of the examination. It also is possible
      that this superiority may be related to the algorithms used for SPECT data
      reconstruction. The objective of this investigation was to determine the effect
      of SPECT reconstruction algorithms on the accuracy of MIBI SPECT/CT parathyroid
      imaging. We retrospectively analyzed preoperative MIBI SPECT/CT parathyroid
      imaging studies performed on 106 patients. SPECT data were reconstructed by
      filtered back projection (FBP) and by iterative reconstruction with corrections
      for collimator resolution recovery and attenuation (IRC). Two experienced readers
      independently graded lesion detection certainty on a 5-point scale without
      knowledge of each other's readings, reconstruction methods, other test results or
      final diagnoses. All patients had surgical confirmation of the final diagnosis,
      including disease limited to the neck, and location and weight of excised
      lesion(s). There were 135 parathyroid lesions among the 106 patients. For FBP
      SPECT/CT and IRC SPECT/CT sensitivity was 76% and 90% (p = 0.003), specificity
      was 87% and 87% (p = 0.90), and accuracy was 83% and 88% (p = 0.04),
      respectively. Inter-rater agreement was significantly higher for IRC than for FBP
      (kappa = 0.76, "good agreement", versus kappa = 0.58, "moderate agreement", p <
      0.0001). We conclude that the improved accuracy of MIBI SPECT/CT compared to MIBI
      SPECT for preoperative parathyroid lesion localization is due in part to the use
      of IRC for SPECT data reconstruction. 

PMID- 25973341
TI  - Comparison of FDG-PET/CT images between chronic renal failure patients on
      hemodialysis and controls.
AB  - The whole-body 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) distribution in chronic
      renal failure (CRF) patients on hemodialysis would be different from that in
      subjects with normal renal function, because they lack urinary FDG excretion and
      remain in a constant volume overload. We evaluated the difference in the
      physiological uptake pattern of FDG between chronic renal failure patients on
      hemodialysis and control subjects. The subjects for this retrospective study
      consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24
      age- and sex-matched control subjects (NC group). Standardized uptake values
      normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass
      (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal
      muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal
      aorta, and right atrium were calculated in positron emission tomography/computed
      tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat,
      spleen and right atrium was significantly higher in the HD group as compared to
      that in the NC group (p < 0.05; unpaired t test). In addition, SUVibm, SUVlbm, as
      well as SUVbsa in the abdominal aorta were significantly higher in the HD group
      as compared to those in the NC group (p < 0.05; unpaired t test). In conclusion,
      as compared to normal subjects, chronic renal failure patients on hemodialysis
      show significantly higher physiological FDG uptake in the soft tissues, spleen
      and blood pool. 

PMID- 25973343
TI  - Pharmacologically relevant doses of valproate upregulate CD20 expression in three
      diffuse large B-cell lymphoma patients in vivo.
AB  - BACKGROUND: Epigenetic code modifications by histone deacetylase inhibitors
      (HDACi) have been proposed as potential new therapies for lymphoid malignancies.
      Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive
      lymphoma for which standard first line treatment is the chemotherapy regimen CHOP
      (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the
      monoclonal anti-CD20 antibody rituximab (R-CHOP). The HDACi valproate, which has
      for long been utilized in anti-convulsive therapy, has been shown to sensitize to
      chemotherapy in vitro. Valproate upregulates expression of CD20 in lymphoma cell
      lines; therefore, 48 hour pre-treatment with valproate before first line R-CHOP
      in DLBCL stages II-IV is evaluated in the phase I clinical trial VALFRID;
      Valproate as First line therapy in combination with Rituximab and CHOP in Diffuse
      large B-cell lymphoma. FINDINGS: Pretreatment with valproate at oral doses
      comparable to anti-convulsive therapy, resulted in upregulation of CD20 mRNA and
      CD20 protein on the cell surface as measured by qPCR and FACS analysis in
      lymphoma biopsies from three evaluated patients from the VALFRID study. Valproate
      treatment corresponded to increased acetylation of Histone3Lysine9 (H3K9ac) in
      peripheral blood mononuclear cells (PBMCs), which were employed as surrogate
      tissue for valproate-related epigenetic modifications. CONCLUSIONS: Valproate
      treatment at pharmacologically relevant doses resulted in upregulation of CD20 in
      vivo, and also in expected epigenetic modifications. This suggests that pre
      treatment with valproate or other HDACis before anti-CD20 therapy could be
      advantageous in CD20-low B-cell lymphomas. Further studies are warranted to
      evaluate this conclusion.

PMID- 25973344
TI  - Zebrafish Renal Pathology: Emerging Models of Acute Kidney Injury.
AB  - The renal system is vital to maintain homeostasis in the body, where the kidneys
      contain nephron functional units that remove metabolic waste from the
      bloodstream, regulate fluids, and balance electrolytes. Severe organ damage from
      toxins or ischemia that occurs abruptly can cause acute kidney injury (AKI) in
      which there is a rapid, life-threatening loss of these activities. Humans have a
      limited but poorly understood ability to regenerate damaged nephrons after AKI.
      However, researchers studying AKI in vertebrate animal models such as mammals,
      and more recently the zebrafish, have documented robust regeneration within the
      nephron blood filter and tubule following injury. Further, zebrafish kidneys
      contain progenitors that create new nephrons after AKI. Here, we review
      investigations in zebrafish which have established a series of exciting renal
      pathology paradigms that complement existing AKI models and can be implemented to
      discover insights into kidney regeneration and the roles of stem cells.

PMID- 25973347
TI  - Nd: YAG Laser Treatment for Keloids and Hypertrophic Scars: An Analysis of 102
      Cases: Erratum.

PMID- 25973346
TI  - INVESTIGATING THE EFFICACY OF CLINICAL TRIAL MONITORING STRATEGIES: Design and
      Implementation of the Cluster Randomized START Monitoring Substudy.
AB  - BACKGROUND: Trial monitoring protects participant safety and study integrity.
      While monitors commonly go on-site to verify source data, there is little
      evidence that this practice is efficient or effective. An ongoing international
      HIV treatment trial (START) provides an opportunity to explore the usefulness of
      different monitoring approaches. METHODS: All START sites are centrally monitored
      and required to follow a local monitoring plan requiring specific quality
      assurance activities. Additionally, sites were randomized (1:1) to receive, or
      not receive, annual on-site monitoring. The study will determine if on-site
      monitoring increases the identification of major protocol deviations (eligibility
      or consent violations, improper study drug use, primary or serious event
      underreporting, data alteration or fraud). RESULTS: The START study completed
      enrollment in December 2013, with planned follow-up through December 2016. The
      monitoring study is ongoing at 196 sites in 34 countries. Results are expected
      when the START study concludes in December 2016.

PMID- 25973345
TI  - Key Fibrogenic Signaling.
AB  - Fibrosis is defined as an excessive accumulation of extracellular matrix
      components that lead to the destruction of organ architecture and impairment of
      organ function. Moreover, fibrosis is an intricate process attributable to a
      variety of interlaced fibrogenic signals and intrinsic mechanisms of activation
      of myofibroblasts. Being the dominant matrix-producing cells in organ fibrosis,
      myofibroblasts may be differentiated from various types of precursor cells.
      Identification of the signal pathways that play a key role in the pathogenesis of
      fibrotic diseases may suggest potential therapeutic targets. Here, we emphasize
      several intracellular signaling pathways that control the activation of
      myofibroblasts and matrix production.

PMID- 25973348
TI  - Gold nanoparticle-assisted selective photothermolysis of adipose tissue
      (NanoLipo) Publication information: Erratum.

PMID- 25973349
TI  - Treatment of skin avulsion injuries with basic fibroblast growth factor.
AB  - This report describes favorable outcomes in 9 patients with skin avulsion
      injuries of the extremities who underwent full-thickness skin grafting and basic
      fibroblast growth factor (bFGF) application. Following removal of contaminated
      subcutaneous fat tissue on the inside of skin, the avulsed skin was processed
      into a full-thickness skin graft, with as much of the skin used as possible
      irrespective of damage. Several drainage holes (5-10 mm in diameter) were made on
      the graft for drainage from the graft bed and to prevent seroma and hematoma
      formation. Genetically recombinant human bFGF was sprayed at a dose of 1
      MUg/cm(2) onto the graft bed, which was then covered with the graft and sutured.
      Pressure immobilization with ointment gauzes and elastic bandages was
      administered for 1 week postoperatively, and the surface of the skin grafts that
      did not take was scraped away, preserving the revascularized dermal component on
      the debrided raw surface as much as possible. bFGF was sprayed again onto the
      debrided surface to promote epithelialization. Wound closure was achieved in all
      cases with conservative therapy. The surgical procedure was effective in
      preventing postoperative ulcer formation and scar contracture and resulted in
      wound healing with the formation of good-quality, flexible scars. 

PMID- 25973350
TI  - Indications and Outcomes of Prophylactic and Therapeutic Extracranial-to
      intracranial Arterial Bypass for Cerebral Revascularization.
AB  - BACKGROUND: Extracranial-to-intracranial (EC-IC) arterial bypass is a technically
      demanding procedure used to treat complex cerebral artery diseases. The
      indications, proper surgical techniques, and outcomes of this procedure have been
      under debate over the recent decades. METHODS: Between January 2004 and December
      2012, 28 patients, including patients with cerebral artery occlusion,
      intracranial aneurysm, cranial base tumor, and Moyamoya disease, underwent EC-IC
      bypass. Patients' records were retrospectively reviewed for demography,
      indications, complications, high-flow versus low-flow bypass, patency rate of
      bypass, and neurological outcome. The patients were sorted into prophylactic (n =
      16) and therapeutic (n = 12) groups based on the preoperative presentation of
      their neurological symptoms. Follow-up evaluation was performed at a mean of 32.7
      +/- 24.3 months. RESULTS: The overall patency rate of bypass was 100%, the
      postoperative stroke rate was zero, and the surgical complication rate was 14.3%.
      There was no significant difference in the bypass patency rate between the 2
      groups or between the high-flow and low-flow bypass patients. Patients who
      underwent prophylactic bypass had minimal surgical and total complications (P =
      0.03 and P < 0.01, respectively) and a better neurological outcome. Surgical
      complications were more common in patients who underwent therapeutic bypass
      (25%). CONCLUSIONS: The collaboration of neurosurgeons and plastic surgeons in
      performing EC-IC bypass can result in excellent outcomes with a high bypass
      patency rate and few complications, particularly for prophylactic EC-IC bypass.

PMID- 25973351
TI  - One-flap Palatoplasty: A Cohort Study to Evaluate a Technique for Unilateral
      Cleft Palate Repair.
AB  - BACKGROUND: The 2-flap palatoplasty technique is actually the approach most
      commonly used in the United States for cleft palate repair. This is a one-time
      surgery that enables closure under minimal tension, lowering rates of subsequent
      fistula development. However, its primary disadvantage is potential detriment to
      maxillary growth (due to extent of dissection on both sides of the cleft and raw
      lateral surfaces). Since 2007, a surgical technique using only one mucoperiosteal
      flap from the noncleft side has been performed by us, reducing the extent of the
      surgery and its potential nondesirable effects over the palate. The purpose of
      this study is to evaluate the utility of this technique for unilateral cleft
      palate repair. METHODS: This is a retrospective, simple-blinded cohort study
      between 2 groups of 120 patients each with unilateral cleft palate who were
      operated on using the 2-flap and 1-flap techniques by the Outreach Surgical
      Center Program Lima from 2007 to 2012. Data collection was accomplished by
      physical examination to evaluate the presence or absence of a fistula and to
      evaluate the presence of hypernasality. Postoperative bleeding was also studied.
      RESULTS: We have observed no increase in the rate of fistulas and velopharyngeal
      insufficiency between these 2 studied groups (P = 0.801 and P = 1.000).
      CONCLUSIONS: Use of a 1-flap technique for unilateral cleft palate repair allowed
      us to achieve results comparable to those of a 2-flap technique in terms of
      postoperative fistula development and hypernasal speech. Additional studies are
      required to evaluate the effect of this technique on palatal growth.

PMID- 25973352
TI  - Use of a myringotome for percutaneous fasciotomies: a technical tip for assisting
      lipofilling.

PMID- 25973353
TI  - Surgical excision of madelung disease using bilateral cervical lymphnode
      dissection technique-its effect and the influence of previous injection
      lipolysis.
AB  - Madelung disease, also known as benign symmetrical lipomatosis, is a rare
      condition characterized by symmetrical diffuse adipose tissue in the neck,
      shoulders, and arms. The present report described the case of a 51-year-old man
      diagnosed with Madelung disease who presented with masses primarily in the neck.
      He had previously shown partial improvement after injection lipolysis and
      shoulder surgery. However, 4 years later, following corticosteroid administration
      for the treatment of acute deafness, cervical lipomatosis progressed to the
      extent that he was unable to fasten his shirt. The initial treatment plan
      involved bilateral surgical excision of the lipomatous masses of the neck and
      liposuction for those in the submental area. However, the lipomas were adherent
      to the surrounding tissue and were partially fibrosed, presumably due to the
      previous injection lipolysis; thus, liposuction was not possible, and all the
      masses around the neck were carefully excised using cervical lymph node
      dissection technique. Thirty-two months later, the patient showed good cosmetic
      results, with no recurrence of cervical lipomatosis. Radical resection of the
      lipomas using a cervical dissection technique is useful in the treatment of
      Madelung disease; however, clinicians must consider the potential for adhesions
      and plan a meticulous dissection in those who have undergone injection lipolysis
      before the surgery. 

PMID- 25973354
TI  - The microsurgery fellowship at chang gung memorial hospital: blossom of
      caterpillars.
AB  - Against a background of globalization and medical migration, issues have been
      raised regarding training outside the clinician's own context. Fellowship was not
      commonly used as a career step, or a means of migration, but as a process of
      professional and personal development. Taking Chang Gung Memorial Hospital
      Microsurgery Fellowship as the case study, I would like to highlight an example
      of a long-running successful training program in a special field such as plastic
      surgery. 

PMID- 25973355
TI  - Hyperkeratotic acral melanoma mimicking a common wart.
AB  - Acral melanoma is a great pretender; anything but i nfrequently, it adopts
      clinical faces, simulating skin conditions that make the healthcare provider
      diagnose it as a benign disease of the palms, soles, and ungual regions. We
      present a case of a hyperkeratotic acral melanoma that has been misdiagnosed and
      that has led to an amputation of the thumb. 

PMID- 25973356
TI  - Electrical burn causing a unique pattern of neurological injury.
AB  - Neurological involvement is not uncommon in patients who sustain electrical
      injury. The exact mechanism of nervous system damage following electrical trauma
      is not fully understood. The gamut of possible neurologic manifestations
      following electrical injury is diverse. This case report describes a young man
      with a unique pattern of neurological injury following an electrical burn. The
      combination of brachial plexopathy, partial Horner's syndrome, and phrenic nerve
      palsy secondary to electrical injury has not been previously described in the
      literature. 

PMID- 25973357
TI  - Secure fixation of a nasal cannula in orthognathic surgery using a swimming cap.

PMID- 25973358
TI  - Nipple-areolar Complex Reconstruction following Postmastectomy Breast
      Reconstruction: A Comparative Utility Assessment Study.
AB  - BACKGROUND: Nipple-areola complex (NAC) reconstruction occurs toward the final
      stage of breast reconstruction; however, not all women follow through with these
      procedures. The goal of this study was to determine the impact of the health
      state burden of living with a reconstructed breast before NAC reconstruction.
      METHODS: A sample of the population and medical students at McGill University
      were recruited to establish the utility scores [visual analog scale (VAS), time
      trade-off (TTO), and standard gamble (SG)] of living with an NAC deformity.
      Utility scores for monocular and binocular blindness were determined for
      validation and comparison. Linear regression and Student's t test were used for
      statistical analysis, and significance was set at P < 0.05. RESULTS: There were
      103 prospective volunteers included. Utility scores (VAS, TTO, and SG) for NAC
      deformity were 0.84 +/- 0.18, 0.92 +/- 0.11, and 0.92 +/- 0.11, respectively.
      Age, gender, and ethnicity were not statistically significant independent
      predictors of utility scores. Income thresholds of <$10,000 and >$10,000 revealed
      a statistically significant difference for VAS (P = 0.049) and SG (P = 0.015).
      Linear regression analysis showed that medical education was directly
      proportional to the SG and TTO scores (P < 0.05). CONCLUSIONS: The absence of NAC
      in a reconstructed breast can be objectively assessed using utility scores (VAS,
      0.84 +/- 0.18; TTO, 0.92 +/- 0.11; SG, 0.92 +/- 0.11). In comparison to prior
      reported conditions, the quality of life in patients choosing to undergo NAC
      reconstruction is similar to that of persons living with a nasal deformity or an
      aging neck requiring rejuvenation.

PMID- 25973359
TI  - Acellular Dermal Matrix in Reconstructive Breast Surgery: Survey of Current
      Practice among Plastic Surgeons.
AB  - BACKGROUND: Acellular dermal matrices (ADMs) in plastic surgery have become
      increasingly popular particularly for breast reconstruction. Despite their
      advantages, questions exist regarding their association with a possible increased
      incidence of complications. We describe a collective experience of plastic
      surgeons' use of ADMs in reconstructive breast surgery using an internet-based
      survey. METHODS: Members of the American Society of Plastic Surgeons were
      recruited through voluntary, anonymous participation in an online survey. The web
      based survey garnered information about participant demographics and their
      experience with ADM use in breast reconstruction procedures. After responses were
      collected, all data were anonymously processed. RESULTS: Data were ascertained
      through 365 physician responses of which 99% (n = 361) completed the survey. The
      majority of participants were men (84.5%) between 51 and 60 years (37.4%); 84.2%
      used ADM in breast reconstruction, including radiated patients (79.7%). ADM use
      was not favored for nipple reconstruction (81.5%); 94.6% of participants used
      drains, and 87.8% administered antibiotics postoperatively. The most common
      complications were seroma (70.9%) and infection (16%), although 57.4% claimed
      anecdotally that overall complication rate was unchanged after incorporating ADM
      into their practice. High cost was a deterrent for ADM use (37.5%). CONCLUSIONS:
      Plastic surgeons currently use ADM in breast reconstruction for both immediate
      and staged procedures. Of those responding, a majority of plastic surgeons will
      incorporate drains and use postoperative antibiotics for more than 48 hours.

PMID- 25973360
TI  - Performance of the high-resolution atmospheric model HRRR-AK for correcting
      geodetic observations from spaceborne radars.
AB  - [1] Atmospheric phase delays are considered to be one of the main performance
      limitations for high-quality satellite radar techniques, especially when applied
      to ground deformation monitoring. Numerical weather prediction (NWP) models are
      widely seen as a promising tool for the mitigation of atmospheric delays as they
      can provide knowledge of the atmospheric conditions at the time of Synthetic
      Aperture Radar data acquisition. However, a thorough statistical analysis of the
      performance of using NWP production in radar signal correction is missing to
      date. This study provides a quantitative analysis of the accuracy in using
      operational NWP products for signal delay correction in satellite radar geodetic
      remote sensing. The study focuses on the temperate, subarctic, and Arctic climate
      regions due to a prevalence of relevant geophysical signals in these areas. In
      this study, the operational High Resolution Rapid Refresh over the Alaska region
      (HRRR-AK) model is used and evaluated. Five test sites were selected over Alaska
      (AK), USA, covering a wide range of climatic regimes that are commonly
      encountered in high-latitude regions. The performance of the HRRR-AK NWP model
      for correcting absolute atmospheric range delays of radar signals is assessed by
      comparing to radiosonde observations. The average estimation accuracy for the one
      way zenith total atmospheric delay from 24 h simulations was calculated to be
      better than ~14 mm. This suggests that the HRRR-AK operational products are a
      good data source for spaceborne geodetic radar observations atmospheric delay
      correction, if the geophysical signal to be observed is larger than 20 mm.

PMID- 25973361
TI  - The Relationship Between Perceived Racism/Discrimination and Health Among Black
      American Women: a Review of the Literature from 2003 to 2013.
AB  - OBJECTIVES: The purpose of this paper was to systematically review the literature
      investigating the relationship between perceived racism/discrimination and health
      among black American women. METHODS: Searches for empirical studies published
      from January 2003 to December 2013 were conducted using PubMed and PsycInfo.
      Articles were assessed for possible inclusion using the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) 2009 framework. In addition,
      the Agency for Healthcare Research and Quality (AHRQ) system for rating the
      strength of scientific evidence was used to assess the quality of studies
      included in the review. RESULTS: Nineteen studies met criteria for review. There
      was mixed evidence for general relationships between perceived
      racism/discrimination and health. Consistent evidence was found for the
      relationship between adverse birth outcomes, illness incidence, and cancer or
      tumor risk and perceived racism/discrimination. Inconsistent findings were found
      for the relationship between perceived racism/discrimination and heart disease
      risk factors. There was no evidence to support the relationship between perceived
      racism/discrimination and high blood pressure. CONCLUSIONS: There is mixed
      evidence to support the association between perceived racism/discrimination and
      overall objective health outcomes among black American women. The strongest
      relationship was seen between perceived racism/discrimination and adverse birth
      outcomes. Better understanding of the relationship between health and
      racism/discrimination can aid in identifying race-based risk factors developing
      primary prevention strategies. Future studies should aim to investigate the role
      of perceived racism/discrimination as a specific chronic stressor within discrete
      pathogenesis models.

PMID- 25973362
TI  - Oligomerized CARD16 promotes caspase-1 assembly and IL-1beta processing.
AB  - Increasing evidence indicates that caspase recruitment domain (CARD)-mediated
      caspase-1 (CASP1) assembly is an essential process for its activation and
      subsequent interleukin (IL)-1beta release, leading to the initiation of
      inflammation. Both CARD16 and CARD17 were previously reported as inhibitory
      homologs of CASP1; however, their molecular function remains unclear. Here, we
      identified that oligomerization activity allows CARD16 to function as a CASP1
      activator. We investigated the molecular characteristics of CARD16 and CARD17 in
      transiently transfected HeLa cells. Although both CARD16 and CARD17 interacted
      with CASP1CARD, only CARD16 formed a homo-oligomer. Oligomerized CARD16 formed a
      filament-like structure with CASP1CARD and a speck with apoptosis-associated
      speck-like protein containing a CARD. A filament-like structure formed by CARD16
      promoted CASP1 filament assembly and IL-1beta release. In contrast, CARD17 did
      not form a homo-oligomer or filaments and inhibited CASP1-dependent IL-1beta
      release. Mutated CARD16D27G, mimicking the CARD17 amino acid sequence, formed a
      homo-oligomer but failed to form a filament-like structure. Consequently,
      CARD16D27G weakly promoted CASP1 filament assembly and subsequent IL-1beta
      release. These results suggest that oligomerized CARD16 promotes CARD-mediated
      molecular assembly and CASP1 activation. 

PMID- 25973363
TI  - Differential adaptive responses to 1- or 2-day fasting in various mouse tissues
      revealed by quantitative PCR analysis.
AB  - Dietary or caloric restriction confers various clinical benefits. Short-term
      fasting of mice is a common experimental procedure that may involve systemic
      metabolic remodeling, which may significantly affect experimental outputs. This
      study evaluated adaptive cellular responses after 1- or 2-day fasting in 13 mouse
      tissues by quantitative PCR using 15 marker primer sets for the activation of
      ubiquitin-proteasome (Atrogin-1 and MuRF1), autophagy-lysosome (LC3b, p62 and
      Lamp2), amino acid response (Asns, Trib3, Herpud1, xCT, and Chop), Nrf2-mediated
      antioxidant (HO-1 and Gsta1), and amino acid transport (Slc38a2, Slc7a5, and
      Slc7a1) systems. Differential activation profiles obtained in seven highly
      (thymus, liver, spleen, and small intestine) or mildly (stomach, kidney, and
      colon) atrophied tissues as well as in six non-atrophied tissues (brain, eye,
      lung, heart, skeletal muscle, and testis) suggested tissue-specific active
      metabolic remodeling. 

PMID- 25973364
TI  - Functional roles of N-terminal and C-terminal domains in the overall activity of
      a novel single-stranded DNA binding protein of Deinococcus radiodurans.
AB  - Single-stranded DNA binding protein (Ssb) of Deinococcus radiodurans comprises N-
      and C-terminal oligonucleotide/oligosaccharide binding (OB) folds connected by a
      beta hairpin connector. To assign functional roles to the individual OB folds, we
      generated three Ssb variants: SsbN (N-terminal without connector), SsbNC (N
      terminal with connector) and SsbC (C-terminal), each harboring one OB fold. Both
      SsbN and SsbNC displayed weak single-stranded DNA (ssDNA) binding activity,
      compared to the full-length Ssb (SsbFL). The level of ssDNA binding activity
      displayed by SsbC was intermediate between SsbFL and SsbN. SsbC and SsbFL
      predominantly existed as homo-dimers while SsbNC/SsbN formed different oligomeric
      forms. In vitro, SsbNC or SsbN formed a binary complex with SsbC that displayed
      enhanced ssDNA binding activity. Unlike SsbFL, Ssb variants were able to
      differentially modulate topoisomerase-I activity, but failed to stimulate
      Deinococcal RecA-promoted DNA strand exchange. The results suggest that the C
      terminal OB fold is primarily responsible for ssDNA binding. The N-terminal OB
      fold binds weakly to ssDNA but is involved in multimerization. 

PMID- 25973365
TI  - The synaptotagmin juxtamembrane domain is involved in neuroexocytosis.
AB  - Synaptotagmin is a synaptic vesicle membrane protein which changes conformation
      upon Ca(2+) binding and triggers the fast neuroexocytosis that takes place at
      synapses. We have synthesized a series of peptides corresponding to the sequence
      of the cytosolic juxtamembrane domain of synaptotagmin, which is highly conserved
      among different isoforms and animal species, with or without either a hexyl
      hydrophobic chain or the hexyl group plus a fluorescein moiety. We show that
      these peptides inhibit neurotransmitter release, that they localize on the
      presynaptic membrane of the motor axon terminal at the neuromuscular junction and
      that they bind monophosphoinositides in a Ca(2+)-independent manner. Based on
      these findings, we propose that the juxtamembrane cytosolic domain of
      synaptotagmin binds the cytosolic layer of the presynaptic membrane at rest. This
      binding brings synaptic vesicles and plasma membrane in a very close apposition,
      favouring the formation of hemifusion intermediates that enable rapid vesicle
      fusion. 

PMID- 25973366
TI  - Anatomic Double-Bundle Reinsertion After Acute Proximal Anterior Cruciate
      Ligament Injury Using Knotless PushLock Anchors.
AB  - Direct anterior cruciate ligament (ACL) repair has been described with different
      suture techniques after acute ACL injury, but these procedures showed high
      failure rates. Recent studies, however, led to a better understanding of the
      biology of primary ACL healing. This article describes a novel technique
      combining the "healing response technique" with primary anatomic double-bundle
      ACL reinsertion after an acute proximal ACL tear using nonabsorbable No. 2
      FiberWire (Arthrex, Naples, FL) and PushLock knotless suture anchors (Arthrex).
      We recommend this technique for patients with acute proximal avulsion-type ACL
      injuries. Postoperatively, we recommend a knee brace locked in full extension for
      at least 4 weeks to ensure adequate immobilization and then to increase knee
      flexion slowly over the next 4 weeks for subsequent healing of the ACL repair.
      Our technique combines anatomic positioning and reinsertion of the ACL bundles
      with microfracturing of the region delivering stem cells and growth factors to
      the repaired ACL, creating optimal conditions for the healing period. In certain
      cases this technique might be an alternative to conventional ACL reconstruction
      with autograft or allograft tendons. 

PMID- 25973367
TI  - Multiple Looping Technique for Tibial Fixation in Posterior Cruciate Ligament
      Reconstruction of the Knee.
AB  - The outcomes of posterior cruciate ligament reconstruction may be negatively
      affected by insufficient tibial tunnel fixation due to relatively lower bone
      density of the proximal tibia. We introduce a new technique of tibial fixation
      for posterior cruciate ligament reconstruction using free tendon Achilles
      allograft that is less affected by the bone density of the tibial metaphysis. 

PMID- 25973368
TI  - Endoscopic resection of lipoma of the patellar tendon.
AB  - Synovial lipoma of the patellar tendon is a very rare entity. It can be
      associated with rupture of the patellar tendon. We present a case of synovial
      lipoma that was successfully resected endoscopically. The other indications for
      patellar tendoscopy include chronic patellar tendinitis and tendinosis,
      recalcitrant bursitis around the tendon, Osgood-Schlatter disease, and jumper's
      knee. The major potential danger of this endoscopic procedure is iatrogenic
      damage to the patellar insertion during endoscopic debridement in patients with
      jumper's knee or the tibial insertion during endoscopic debridement in patients
      with Osgood-Schlatter disease. 

PMID- 25973370
TI  - Arthroscopic Treatment of Hip Chondral Defects With Bone Marrow Stimulation and
      BST-CarGel.
AB  - Microfracture, the current standard of care for the treatment of non-degenerative
      chondral lesions in the hip joint, is limited by the poor quality of the filling
      fibrocartilaginous tissue. BST-CarGel (Piramal Life Sciences, Laval, Quebec,
      Canada) is a chitosan-based biopolymer that, when mixed with fresh, autologous
      whole blood and placed over the previously microfractured area, stabilizes the
      blood clot and enhances marrow-triggered wound-healing repair processes. BST
      CarGel has been previously applied in the knee, with statistically significant
      greater lesion filling and superior repair tissue quality compared with
      microfracture treatment alone. In this report we describe the application of BST
      CarGel for the arthroscopic treatment of hip chondral lesions. Our preliminary
      data suggest that our BST-CarGel procedure provides high-quality repair tissue
      and therefore may be considered a safe, cost-efficient therapeutic choice for the
      treatment of hip chondral defects. 

PMID- 25973369
TI  - Intra-articular Fluid Distension for Initial Portal Placement During Hip
      Arthroscopy: The "Femoral Head Drop" Technique.
AB  - Iatrogenic injury is a known complication of initial portal placement during hip
      arthroscopy. The rate of labral puncture or damage to the articular surfaces with
      arthroscopic instruments is variable and may be associated with operator
      inexperience or complex anatomy. In addition, the amount of traction applied to
      achieve joint distraction may unnecessarily place patients at risk of
      neurapraxia. The purpose of this article is to describe the "femoral head drop"
      technique as a method to increase safe access to the central compartment and
      minimize the amount of traction needed to do so, especially in patients with
      challenging bony anatomy. This technique uses the application of intra-articular
      saline solution to cause inferior migration of the femoral head. Intra-articular
      fluid distension, or the femoral head drop technique, is simple, safe, and
      reproducible, making it appropriate for hip arthroscopists at any level of
      experience. 

PMID- 25973371
TI  - Acetabular paralabral cyst: an unusual cause of femoral vein compression.
AB  - Acetabular labral tears are a known cause of hip pain in the young, active
      patient. Labral tears can be due to trauma, femoroacetabular impingement,
      capsular laxity, dysplasia, and degenerative pathology. Paralabral cysts are
      relatively common in association with labral tears of the hip, with cysts seen on
      magnetic resonance imaging studies in as many as 50% to 70% of patients with
      labral tears. In some cases the cysts can become sizeable and cause neurovascular
      compression. Nonoperative interventions for the management of paralabral cysts in
      the shoulder and knee have shown high recurrence rates. In the shoulder and knee,
      arthroscopic debridement of paralabral cysts has shown good results with lower
      recurrence rates and resolution of neurovascular function. In the hip there is
      limited literature regarding surgical management of paralabral cysts. We present
      a surgical technique for arthroscopic decompression of acetabular paralabral
      cysts combined with labral repair. 

PMID- 25973372
TI  - Arthroscopic technique for the treatment of pigmented villonodular synovitis of
      the hip.
AB  - Open synovectomy remains the treatment of choice for pigmented villonodular
      synovitis (PVNS) of the hip but has shown modest results compared with the
      treatment of other joints. Recent advances in hip arthroscopy permit a thorough
      evaluation of the joint surfaces, improved access, and decreased postoperative
      morbidity. We describe an arthroscopic synovectomy technique for PVNS of the hip.
      The use of additional arthroscopic portals and creation of a large capsulotomy
      enable successful visualization and extensive synovectomy of the entire synovial
      lining of the hip. The T-capsulotomy enables extensive soft-tissue retraction for
      complete exposure. The midanterior portal enables use of an arthroscopic grasper
      and shaver to directly access and excise the synovial lining of the peripheral
      compartment while avoiding damage to the medial and lateral retinacular vessels.
      Technical innovations in hip arthroscopy have enhanced visualization in the
      central and peripheral compartments, as well as instrument management and
      diagnostic evaluation of the capsule, therefore allowing enhanced management of
      PVNS of the hip. 

PMID- 25973373
TI  - Arthroscopic transosseous bony bankart repair.
AB  - Restoration of glenoid bony integrity is critical to minimizing the risk of
      recurrence and re-creating normal kinematics in the setting of anterior
      glenohumeral instability. We present an arthroscopic suture anchor-based
      technique for treating large bony Bankart fractures in which the fragment is
      secured to the intact glenoid using mattress sutures placed through the bony
      fragment and augmented with soft-tissue repair proximal and distal to the bony
      lesion. This straightforward technique has led to excellent fragment reduction
      and good outcomes in our experience. 

PMID- 25973374
TI  - Arthroscopic-assisted reduction and percutaneous fixation of tibial plateau
      fractures.
AB  - Tibial plateau fractures present a difficult range of fractures to treat.
      Arthroscopy allows for a less invasive option when compared with arthrotomy.
      Furthermore, visualization of the articular surface arthroscopically can allow
      for a precise reduction and assessment of any concomitant injuries to the
      articular cartilage and meniscus. By use of arthroscopy, unicondylar lateral
      plateaus were traditionally approached through a laterally based metaphyseal
      window. However, in carefully selected patients and fracture patterns, a medially
      based, arthroscopic-assisted approach can create long bony tunnels for
      subchondral support and allow for greater ease in fracture reduction. We present
      our technique using a medial approach for arthroscopic-assisted fixation of
      lateral tibial plateau fractures. 

PMID- 25973375
TI  - Anatomic reconstruction of the medial patellofemoral ligament using the fascia
      lata as an autograft.
AB  - The medial patellofemoral ligament (MPFL) ensures stability of the patella
      against lateral forces. In cases of recurrent lateral patellar luxation, surgical
      reconstruction of the MPFL has an important role in treating lateral patellar
      instability. Several biomechanical studies have presented valuable pieces of
      information about various techniques for re-creating this medial patellofemoral
      complex mainly using the gracilis tendon as an autograft. However, with the
      increasing number of MPFL reconstructions, there are also an increasing number of
      patients requiring revision MPFL reconstruction. Therefore alternative graft
      options may become more relevant. Furthermore, the gracilis tendon as a tubular
      graft may not be able to fully restore patellofemoral kinematics compared with
      the native MPFL. This article introduces a surgical technique using the fascia
      lata as an alternative graft option for the anatomic reconstruction of the MPFL. 

PMID- 25973376
TI  - Double-Barrel Remplissage: An Arthroscopic All-Intra-articular Technique Using
      the Double-Barrel Knot for Anterior Shoulder Instability.
AB  - The arthroscopic remplissage procedure is an effective addition to a standard
      anterior repair in traumatic anterior shoulder instability associated with large
      humeral defects. The double-barrel remplissage is an all-intra-articular
      technique that uses a double-pulley, sliding, and self-retaining knot mechanism
      called the double-barrel knot. A 70 degrees  arthroscope (posterior portal) is
      necessary for adequate visualization of the humeral defect and the rotator cuff.
      Trans-tendon anchors (single or double loaded) are inserted into the superior and
      inferior aspects of the humeral defect through a cannula that is placed posterior
      to the infraspinatus. Placement of anchors is facilitated by insertion of a
      guidewire, as well as an anchor sleeve that is threaded over it. The double
      barrel knot is formed using the anchors as a double-pulley system, and the knot
      is tensioned after the anterior repair is complete. Intra-articular visualization
      confirms adequate approximation and compression of the infraspinatus tendon and
      capsule into the defect. Advantages include an increased surface area (footprint)
      for healing and ease of knotting without the necessity for additional subacromial
      dissection. 

PMID- 25973377
TI  - Circumferential rotator cuff repair with the n+4 portal, subclavian portal, and
      high posteromedial portal.
AB  - Passing suture during a rotator cuff repair requires proper orientation and
      purchase of the rotator cuff tendon. Our technique uses a new portal to improve
      access to the supraspinatus and infraspinatus and uses additional portals for a
      circumferential repair of the tear, thereby restoring the footprint. Using a
      penetrating suture passer through the anterior, posterior, and superomedial
      portals allows 270 degrees  of coverage. The lateral anchors complete the
      circumferential repair. Sutures from the medial anchors are passed in a
      retrograde fashion using 3 small incisions with no cannula. A spinal needle is
      used to localize the orientation of each portal. The N+4 portal is the workhorse
      portal, allowing access to the supraspinatus and infraspinatus. The suture
      retriever enters the trapezius 5 cm from the medial border of the acromion and 1
      cm anterior to the spine of the scapula. It enters the subacromial space on top
      of the supraspinatus. This provides protection to the suprascapular nerve in the
      supraspinatus fossa. The cuff is lifted with a grasper to allow perpendicular
      passage of suture. The suture is retrieved for tying. The tissue purchase and
      location of suture placement help restore the footprint of the supraspinatus and
      infraspinatus. Additional sutures are passed anteriorly through the subclavian
      portal and posteriorly through the high posteromedial portal. The repair is
      completed with lateral-row anchors as needed. 

PMID- 25973378
TI  - Arthroscopic capsule reconstruction in the hip using iliotibial band allograft.
AB  - The hip capsule has been identified as an important static stabilizer of the hip
      joint. Despite the intrinsic bony stability of the hip socket, the capsule plays
      a key role in hip stability, particularly at the extremes of motion, and the
      iliofemoral ligament is the most important stabilizer in extension and external
      rotation. Patients who do not undergo capsular closure or plication may continue
      to complain of hip pain and dysfunction postoperatively, likely because of
      microinstability or muscle invagination into the capsular defect, and high
      resolution magnetic resonance imaging or magnetic resonance arthrography will
      identify the capsular defect. Seen primarily in the revision setting, capsular
      defects can cause recurrent stress at the chondrolabral junction. An attempt at
      secondary closure can be challenging because of capsular limb adherence to the
      surrounding soft tissues. Therefore reconstruction may be the only possible
      surgical solution for this problem. We describe our new surgical technique for
      arthroscopic hip capsular reconstruction using iliotibial band allograft. 

PMID- 25973379
TI  - Ankle arthroscopy for ankle fractures.
AB  - In many patients who undergo open reduction-internal fixation of ankle fractures,
      there is a failure to achieve good clinical outcomes despite radiographic
      evidence of anatomic reduction. One possible reason for this is the high
      incidence of concomitant intra-articular pathology associated with ankle
      fractures that may go unrecognized using traditional open approaches. Arthroscopy
      in the setting of acute operative management of ankle fractures provides a means
      to completely assess intra-articular pathology, as well as provide direct
      therapeutic intervention in many instances. Arthroscopic management techniques
      include debridement of loose intra-articular fragments, assisted fracture
      reduction, microfracture of chondral injuries, and assessment of syndesmotic
      stability. The indications for arthroscopy in the setting of ankle fractures have
      not been fully defined; however, it is our practice to perform an arthroscopic
      assessment of all ankle fractures requiring surgical intervention. We present a
      sample of our experience using this technique that shows the severity of intra
      articular pathology that is often found and occurs even in association with
      fracture patterns with seemingly innocuous radiographic appearances. 

PMID- 25973380
TI  - Arthroscopic reduction and internal fixation for fracture of the lateral process
      of the talus.
AB  - Fractures of the lateral process of the talus (LPT) are relatively rare. We
      describe arthroscopic reduction and internal fixation for a type I fracture of
      the LPT according to the Hawkins classification. Preoperative computed tomography
      is necessary to evaluate the type and displacement of the LPT fracture because
      this type of fracture is often overlooked on a plain radiograph. The ankle is
      approached through a standard medial portal as the working portal and an
      anterolateral portal as the viewing portal. A 2.7-mm-diameter 30 degrees 
      arthroscope is used. Hematoma and soft tissues around the talus are cleared with
      a motorized shaver, and the anterior and lateral aspects of the talar process are
      visualized. Fracture reduction is obtained by pushing the lateral fragment of the
      lateral process medially and is fixed temporally with a 1.1-mm guidewire from the
      medial portal under both arthroscopy and fluoroscopy. A headless compression
      screw is inserted through the guidewire. Arthroscopic reduction and internal
      fixation for a type I LPT fracture can be easily accomplished, and return to
      daily and sports activities can be achieved in a relatively short time. 

PMID- 25973381
TI  - Trochanteric micropuncture: treatment for gluteus medius tendinopathy.
AB  - Lateral hip pain along with tenderness of the greater trochanter has been
      associated with greater trochanteric pain syndrome. Radiographically, this has
      been associated with gluteus medius pathology on magnetic resonance imaging. This
      has led some surgeons to conclude that abductor pathology is a primary cause of
      lateral hip pain. Failure of conservative treatment in the setting of gluteus
      medius pathology may lead to surgical intervention. In some patients a focal tear
      of the gluteus medius cannot be visualized and likely represents more diffuse
      tendinopathy. In these patients we propose micropuncture of the greater
      trochanter. Similar procedures have shown effectiveness in the elbow and shoulder
      by eliciting a healing response. Our experience suggests that trochanteric
      micropuncture at the insertion of the gluteus medius tendon can be effectively
      performed endoscopically for gluteus medius tendinopathy. 

PMID- 25973382
TI  - When pigs fly, UCP1 makes heat.
AB  - Brown and beige adipose tissue may represent important therapeutic targets for
      the treatment of diabetes and obesity as these organs dissipate nutrient energy
      as heat through the thermogenic uncoupling protein 1 (UCP1). While mice are
      commonly used to mimic the potential effects of brown/beige adipose tissue that
      may act in human metabolism, new animal models are edging into the market for
      translational medicine. Pigs reflect human metabolism better than mice in
      multiple parameters such as obesity-induced hyperglycemia, cholesterol profiles
      and energy metabolism. Recently, it was reported that energy expenditure and body
      temperature in pigs is induced by the hormone leptin, and that leptin's action is
      mediated by UCP1 in adipose tissue. Given the tremendous importance of
      identifying molecular mechanisms for targeting therapeutics, we critically
      examine the evidence supporting the presence of UCP1 in pigs and conclude that
      methodological shortcomings prevent an unequivocal claim for the presence of UCP1
      in pigs. Despite this, we believe that leptin's effects on energy expenditure in
      pigs are potentially more transformative to human medicine in the absence of
      UCP1, as adult and obese humans possess only minor amounts of UCP1. In general,
      we propose that the biology of new animal models requires attention to
      comparative studies with humans given the increasing amount of genomic
      information for various animal species. 

PMID- 25973383
TI  - Setting the TRAP for central leptin targets.

PMID- 25973384
TI  - Beyond association: A functional role for Tcf7l2 in beta-cell development.

PMID- 25973385
TI  - De novo lipogenesis in metabolic homeostasis: More friend than foe?
AB  - BACKGROUND: An acute surplus of carbohydrates, and other substrates, can be
      converted and safely stored as lipids in adipocytes via de novo lipogenesis
      (DNL). However, in obesity, a condition characterized by chronic positive energy
      balance, DNL in non-adipose tissues may lead to ectopic lipid accumulation
      leading to lipotoxicity and metabolic stress. Indeed, DNL is dynamically
      recruited in liver during the development of fatty liver disease, where DNL is an
      important source of lipids. Nonetheless, a number of evidences indicates that DNL
      is an inefficient road for calorie to lipid conversion and that DNL may play an
      important role in sustaining metabolic homeostasis. SCOPE OF REVIEW: In this
      manuscript, we discuss the role of DNL as source of lipids during obesity, the
      energetic efficiency of this pathway in converting extra calories to lipids, and
      the function of DNL as a pathway supporting metabolic homeostasis. MAJOR
      CONCLUSION: We conclude that inhibition of DNL in obese subjects, unless coupled
      with a correction of the chronic positive energy balance, may further promote
      lipotoxicity and metabolic stress. On the contrary, strategies aimed at
      specifically activating DNL in adipose tissue could support metabolic homeostasis
      in obese subjects by a number of mechanisms, which are discussed in this
      manuscript.

PMID- 25973386
TI  - Adipocyte SIRT1 knockout promotes PPARgamma activity, adipogenesis and insulin
      sensitivity in chronic-HFD and obesity.
AB  - OBJECTIVE: Adipose tissue is the primary site for lipid deposition that protects
      the organisms in cases of nutrient excess during obesogenic diets. The histone
      deacetylase Sirtuin 1 (SIRT1) inhibits adipocyte differentiation by targeting the
      transcription factor peroxisome proliferator activated-receptor gamma
      (PPARgamma). METHODS: To assess the specific role of SIRT1 in adipocytes, we
      generated Sirt1 adipocyte-specific knockout mice (ATKO) driven by aP2 promoter
      onto C57BL/6 background. Sirt1 (flx/flx) aP2Cre (+) (ATKO) and Sirt1 (flx/flx)
      aP2Cre (-) (WT) mice were fed high-fat diet for 5 weeks (short-term) or 15 weeks
      (chronic-term). Metabolic studies were combined with gene expression analysis and
      phosphorylation/acetylation patterns in adipose tissue. RESULTS: On standard
      chow, ATKO mice exhibit low-grade chronic inflammation in adipose tissue, along
      with glucose intolerance and insulin resistance compared with control fed mice.
      On short-term HFD, ATKO mice become more glucose intolerant, hyperinsulinemic,
      insulin resistant and display increased inflammation. During chronic HFD, WT mice
      developed a metabolic dysfunction, higher than ATKO mice, and thereby, knockout
      mice are more glucose tolerant, insulin sensitive and less inflamed relative to
      control mice. SIRT1 attenuates adipogenesis through PPARgamma repressive
      acetylation and, in the ATKO mice adipocyte PPARgamma was hyperacetylated. This
      high acetylation was associated with a decrease in Ser273-PPARgamma
      phosphorylation. Dephosphorylated PPARgamma is constitutively active and results
      in higher expression of genes associated with increased insulin sensitivity.
      CONCLUSION: Together, these data establish that SIRT1 downregulation in adipose
      tissue plays a previously unknown role in long-term inflammation resolution
      mediated by PPARgamma activation. Therefore, in the context of obesity, the
      development of new therapeutics that activate PPARgamma by targeting SIRT1 may
      provide novel approaches to the treatment of T2DM.

PMID- 25973387
TI  - Nuclear Factor-Y is an adipogenic factor that regulates leptin gene expression.
AB  - OBJECTIVE: Leptin gene expression is highly correlated with cellular lipid
      content in adipocytes but the transcriptional mechanisms controlling leptin
      expression in vivo are poorly understood. In this report, we set out to identify
      cis- and trans-regulatory elements controlling leptin expression. METHODS: Leptin
      BAC luciferase transgenic mice combining with other computational and molecular
      techniques were used to identify transcription regulatory elements including a
      CCAAT-binding protein Nuclear Factor Y (NF-Y). The function of NF-Y in adipocyte
      was studied in vitro with 3T3-L1 cells and in vivo with adipocyte-specific
      knockout of NF-Y. RESULTS: Using Leptin-BAC luciferase mice, we showed that DNA
      sequences between -22 kb and +8.8 kb can confer quantitative expression of a
      leptin reporter. Computational analysis of sequences and gel shift assays
      identified a 32 bp sequence (chr6: 28993820-2899385) consisting a CCAAT binding
      site for Nuclear Factor Y (NF-Y) and this was confirmed by a ChIP assay in vivo.
      A deletion of this 32 bp sequence in the -22 kb to +8.8 kb leptin-luciferase BAC
      reporter completely abrogates luciferase reporter activity in vivo. RNAi mediated
      knockdown of NF-Y interfered with adipogenesis in vitro and adipocyte-specific
      knockout of NF-Y in mice reduced expression of leptin and other fat specific
      genes in vivo. Further analyses of the fat specific NF-Y knockout revealed that
      these animals develop a moderately severe lipodystrophy that is remediable with
      leptin therapy. CONCLUSIONS: These studies advance our understanding of leptin
      gene expression and show that NF-Y controls the expression of leptin and other
      adipocyte genes and identifies a new form of lipodystrophy.

PMID- 25973388
TI  - Mice lacking neutral amino acid transporter B(0)AT1 (Slc6a19) have elevated
      levels of FGF21 and GLP-1 and improved glycaemic control.
AB  - OBJECTIVE: Type 2 diabetes arises from insulin resistance of peripheral tissues
      followed by dysfunction of beta-cells in the pancreas due to metabolic stress.
      Both depletion and supplementation of neutral amino acids have been discussed as
      strategies to improve insulin sensitivity. Here we characterise mice lacking the
      intestinal and renal neutral amino acid transporter B(0)AT1 (Slc6a19) as a model
      to study the consequences of selective depletion of neutral amino acids. METHODS:
      Metabolic tests, analysis of metabolite levels and signalling pathways were used
      to characterise mice lacking the intestinal and renal neutral amino acid
      transporter B(0)AT1 (Slc6a19). RESULTS: Reduced uptake of neutral amino acids in
      the intestine and loss of neutral amino acids in the urine causes an overload of
      amino acids in the lumen of the intestine and reduced systemic amino acid
      availability. As a result, higher levels of glucagon-like peptide 1 (GLP-1) are
      produced by the intestine after a meal, while the liver releases the starvation
      hormone fibroblast growth factor 21 (FGF21). The combination of these hormones
      generates a metabolic phenotype that is characterised by efficient removal of
      glucose, particularly by the heart, reduced adipose tissue mass, browning of
      subcutaneous white adipose tissue, enhanced production of ketone bodies and
      reduced hepatic glucose output. CONCLUSIONS: Reduced neutral amino acid
      availability improves glycaemic control. The epithelial neutral amino acid
      transporter B(0)AT1 could be a suitable target to treat type 2 diabetes.

PMID- 25973389
TI  - Munc18c mediates exocytosis of pre-docked and newcomer insulin granules
      underlying biphasic glucose stimulated insulin secretion in human pancreatic beta
      cells.
AB  - OBJECTIVE: Pancreatic beta-cells express three Munc18 isoforms. Much is known
      about the roles of Munc18a (pre-docked secretory granules-SGs) and Munc18b
      (newcomer SGs and SG-SG fusion) in insulin exocytosis. Although shown to
      influence glucose-stimulated insulin secretion (GSIS) in rodents the precise role
      of Munc18c in insulin SG exocytosis has not been elucidated. We here examined the
      role of Munc18c in human pancreatic beta-cells. METHODS: Munc18c-shRNA/RFP lenti
      virus (versus control virus) was used to knock down the expression level of
      Munc18c in human islets or single beta-cells. Insulin secretion and granule
      exocytosis were measured by performing islets perifusion, single-cell patch clamp
      capacitance measurements and total internal reflection fluorescence microscopy
      (TIRFM). RESULTS: Munc18c is most abundant in the cytosol of human beta-cells.
      Endogenous function of Munc18c was assessed by knocking down (KD) its islet
      expression by 70% employing lenti-shRNA virus. Munc18c-KD caused reduction in
      cognate syntaxin-4 islet expression but not in other exocytotic proteins,
      resulting in the reduction in GSIS in first- (by 42%) and second phases (by 35%).
      Single cell analyses of RFP-tagged Munc18c-KD beta-cells by patch clamp
      capacitance measurements showed inhibition in both readily-releasable pool (by
      52%) and mobilization from the reserve pool (by 57%). TIRFM to assess single SG
      behavior showed that Munc18c-KD inhibition of first phase GSIS was attributed to
      reduction in exocytosis of pre-docked and newcomer SGs, and second phase
      inhibition attributed entirely to reduction in newcomer SG fusion (SGs that
      undergo minimal residence or docking time at the plasma membrane before fusion).
      CONCLUSION: Munc18c is involved in the distinct molecular machineries that affect
      exocytosis of both predocked and newcomer SG pools that underlie Munc18c's role
      in first and second phases of GSIS, respectively.

PMID- 25973391
TI  - Acute myeloid leukemia in a patient with constitutional 47,XXY karyotype.
AB  - Klinefelter syndrome (KS), a 47,XXY chromosomal abnormality, has been shown to be
      associated with a number of malignancies, but has not been linked to acute
      leukemias to date. We present a case of a 54-year-old male diagnosed with acute
      myeloid leukemia (AML) with monocytic differentiation, whose cytogenetic and
      subsequent FISH analyses revealed a constitutional 47,XXY karyotype. We also
      review and discuss relevant prior literature. 

PMID- 25973390
TI  - Activation of natriuretic peptides and the sympathetic nervous system following
      Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning.
AB  - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss
      and remediation of type-2 diabetes; however, the mechanisms leading to these
      improvements are unclear. Additionally, adipocytes within white adipose tissue
      (WAT) depots can manifest characteristics of brown adipocytes. These
      'BRITE/beige' adipocytes express uncoupling protein 1 (UCP1) and are associated
      with improvements in glucose homeostasis and protection from obesity.
      Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige
      adipocyte enrichment of WAT depots, an effect known as "browning." Here, we
      investigate the effect of RYGB surgery on NP, NP receptors, and browning in the
      gonadal adipose tissues of female mice. We propose that such changes may lead to
      improvements in metabolic homeostasis commonly observed following RYGB. METHODS:
      Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six
      months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y
      gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were
      sacrificed six weeks following surgery and evaluated for differences in body
      weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene
      expression. RESULTS: RYGB and calorie restriction induced similar weight loss and
      improved glucose metabolism without decreasing food intake. beta3-adrenergic
      receptor expression increased in gonadal adipose tissue, in addition to Nppb
      (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3
      increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as
      additional markers of BRITE/beige adipose tissue and lipolytic genes increased in
      RYGB mice to a greater extent than calorie-restricted mice. CONCLUSIONS:
      Upregulation of Nppb, Npr1, Npr2, and beta3-adrenergic receptors in gonadal
      adipose tissue following RYGB was associated with increased markers of browning.
      This browning of gonadal adipose tissue may underpin the positive effect of RYGB
      on metabolic parameters and may in part be mediated through upregulation of
      natriuretic peptides.

PMID- 25973392
TI  - Host-parasite interactions during a biological invasion: The fate of lungworms
      (Rhabdias spp.) inside native and novel anuran hosts.
AB  - The cane toad invasion in Australia provides a robust opportunity to clarify the
      infection process in co-evolved versus de novo host-parasite interactions. We
      investigated these infection dynamics through histological examination following
      experimental infections of metamorphs of native frogs (Cyclorana australis) and
      cane toads (Rhinella marina) with Rhabdias hylae (the lungworm found in native
      frogs) and Rhabdias pseudosphaerocephala (the lungworm found in cane toads). Cane
      toads reared under continuous exposure to infective larvae of the frog lungworm
      were examined after periods of 2, 6, 10 and 15 days. Additionally, both toads and
      frogs were exposed for 24 h to larvae of either the toad or the frog lungworm,
      and examined 2, 5, 10 and 20 days post-treatment. R. hylae (frog) lungworms
      entered cane toads and migrated through the body but were not found in the target
      tissue, the lungs. Larvae of both lungworm species induced inflammation in both
      types of hosts, although the immune response (relative numbers of different cell
      types) differed between hosts and between parasite species. Co-evolution has
      modified the immune response elicited by infection and (perhaps for that reason)
      has enhanced the parasite's ability to survive and to reach the host's lungs. 

PMID- 25973394
TI  - Identification of novel Theileria genotypes from Grant's gazelle.
AB  - Blood samples collected from Grant's gazelles (Nanger granti) in Kenya were
      screened for hemoparasites using a combination of microscopic and molecular
      techniques. All 69 blood smears examined by microscopy were positive for
      hemoparasites. In addition, Theileria/Babesia DNA was detected in all 65 samples
      screened by PCR for a ~450-base pair fragment of the V4 hypervariable region of
      the 18S rRNA gene. Sequencing and BLAST analysis of a subset of PCR amplicons
      revealed widespread co-infection (25/39) and the existence of two distinct
      Grant's gazelle Theileria subgroups. One group of 11 isolates clustered as a
      subgroup with previously identified Theileria ovis isolates from small ruminants
      from Europe, Asia and Africa; another group of 3 isolates clustered with
      previously identified Theileria spp. isolates from other African antelope. Based
      on extensive levels of sequence divergence (1.2-2%) from previously reported
      Theileria species within Kenya and worldwide, the Theileria isolates detected in
      Grant's gazelles appear to represent at least two novel Theileria genotypes. 

PMID- 25973393
TI  - A review of neosporosis and pathologic findings of Neospora caninum infection in
      wildlife.
AB  - Neospora caninum is an apicomplexan parasite that is the etiologic agent of
      neosporosis, a devastating infectious disease regarded as a major cause of
      reproductive loss in cattle and neuromuscular disease in dogs worldwide. This
      protozoan pathogen is maintained in the environment by a heteroxenous life cycle
      that involves a definitive canid host and a wide range of intermediate hosts. In
      recent years, a number of wildlife species have been investigated for their
      possible involvement in the N. caninum life cycle and many have been implicated
      as intermediate hosts. However, in many instances these studies have utilized
      serological and molecular techniques to detect infection in clinically normal
      animals, and investigation of possible associated morbidity, mortality, and
      pathology has been neglected. As such, the occurrence and importance of Neospora
      associated disease in wildlife species are unknown. In order to improve our
      understanding of the significance of N. caninum infection in nondomestic species,
      the present review provides an up-to-date summary of clinical neosporosis and N.
      caninum-associated pathologic lesions in naturally and experimentally infected
      wildlife species. We provide a list of all free-ranging and captive wildlife
      species identified with N. caninum infection to date using currently available
      diagnostic tools. The advantages and disadvantages of diagnostic methods in
      wildlife are addressed in order to recommend optimal diagnosis of confirming N.
      caninum infection and neosporosis in nondomestic species. Although current data
      would suggest that N. caninum infection does not adversely impact wildlife
      populations, there is a need for greater international uniformity in the
      diagnosis of N. caninum infection and neosporosis in nondomestic species in order
      to assess the true consequences of parasite infection. 

PMID- 25973396
TI  - Is the concept of central nervous system immune privilege irrelevant in the
      setting of acute infection?

PMID- 25973397
TI  - Hsp90, the concertmaster: tuning transcription.
AB  - In the last decade, Hsp90 has emerged as a major regulator of cancer cell growth
      and proliferation. In cancer cells, it assists in giving maturation to oncogenic
      proteins including several kinases and transcription factors (TF). Recent studies
      have shown that apart from its chaperone activity, it also imparts regulation of
      transcription machinery and thereby alters the cellular physiology. Hsp90 and its
      co-chaperones modulate transcription at least at three different levels. In the
      first place, they alter the steady-state levels of certain TFs in response to
      various physiological cues. Second, they modulate the activity of certain
      epigenetic modifiers, such as histone deacetylases or DNA methyl transferases,
      and thereby respond to the change in the environment. Third, they participate in
      the eviction of histones from the promoter region of certain genes and thereby
      turn on gene expression. In this review, we discuss the role of Hsp90 in all the
      three aforementioned mechanisms of transcriptional control, taking examples from
      various model organisms with a special emphasis on cancer progression. 

PMID- 25973398
TI  - Editorial: the oral microbiome in an ecological perspective.

PMID- 25973399
TI  - Brainstem evoked potential in newly diagnosed patients of subclinical
      hypothyroidism.
AB  - BACKGROUND: Hypothyroidism is known to be associated with impairment of hearing.
      The hearing impairment may be conductive, sensorineural, or mixed. AIMS: The aim
      is to assess the auditory pathway by brainstem auditory evoked potentials (BAEPs)
      in newly diagnosed patients of subclinical hypothyroidism and healthy sex- and
      age-matched controls. MATERIALS AND METHODS: The study included 25 healthy sex-
      and age-matched controls (Group I) and 25 patients of newly diagnosed subclinical
      hypothyroidism (Group II). The recording was taken by using RMS EMG EP MK2
      equipment. The unpaired Student's t-test was used and a P value <0.05 was
      considered significant. RESULTS: Wave V of right ear BAEP in group II was
      prolonged (6 +/- 0.62 ms) compared to group I (5.49 +/- 0.26 ms), and wave V of
      left ear BAEP in group II was prolonged (5.84 +/- 0.57 ms) compared to group I
      (5.47 +/- 0.35 ms). There was no significant coefficient of correlation between
      wave V and inter-peak latency (IPL) I-V compared to thyroid-stimulating hormone
      (TSH) levels of both the ears. CONCLUSION: The prolongation of wave V in BAEPs of
      both ears suggests that the central auditory pathway is affected significantly in
      subclinical hypothyroid patients.

PMID- 25973400
TI  - Role of Brain Perfusion SPECT with 99mTc HMPAO in the Assessment of Response to
      Drug Therapy in Patients with Autoimmune Vasculitis: A Prospective Study.
AB  - BACKGROUND: The diagnosis of vasculitis in the brain remains a quite difficult
      achievement. To the best of our knowledge, there is no imaging method reported in
      literature which is capable of reaching to a diagnosis of vasculitis with very
      high sensitivity. AIM: The aim of this study was to determine whether perfusion
      brain single photon emission computed tomography (SPECT) can be usefully employed
      in monitoring the treatment of vasculitis, allowing treating only potentially
      responder patients and avoiding the side effects on patients who do not respond.
      MATERIALS AND METHODS: Twenty patients (two males and 18 females) suffering from
      systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5),
      undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were
      included in the study. All patients underwent a wide neurological anamnestic
      investigation, a complete objective neurological examination and SPECT of the
      brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then
      repeated after appropriate medical treatment. The neurological and
      neuropsychiatric follow-up was performed at 6 months after the start of the
      treatment. RESULTS: Overall, the differences between the scintigraphic results
      obtained after and before the medical treatment indicated a statistically
      significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of
      interest (ROI) studied, the difference between pre- and post treatment
      percentages had negative sign, indicating a worsening of CP. This latter event
      has occurred six times (five in the same patients) in the UV, 10 times (eight in
      the same patients) in the SLE, never in BD, and three times (two in the same
      patient) in the SS. CONCLUSION: The reported results seem to indicate the
      possibility of identifying, by the means of a brain SPECT, responder and
      nonresponder (unchanged or worsened CP) patients, affected by autoimmune
      vasculitis, to the therapy.

PMID- 25973395
TI  - Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human
      Cancer.
AB  - The current understanding of the molecular mechanisms that lead to cancer is not
      sufficient to explain the loss or gain of function in proteins related to
      tumorigenic processes. Among them, more than 100 oncogenes, 20-30 tumor
      suppressor genes, and hundreds of genes participating in DNA repair and
      replication have been found to play a role in the origins of cancer over the last
      25 years. The phosphorylation of serine, threonine, or tyrosine residues is a
      critical step in cellular growth and development and is achieved through the
      tight regulation of protein kinases. Phosphorylation plays a major role in
      eukaryotic signaling as kinase domains are found in 2% of our genes. The
      deregulation of kinase control mechanisms has disastrous consequences, often
      leading to gains of function, cell transformation, and cancer. The c-Abl kinase
      protein is one of the most studied targets in the fight against cancer and is a
      hotspot for drug development because it participates in several solid tumors and
      is the hallmark of chronic myelogenous leukemia. Tumor suppressors have the
      opposite effects. Their fundamental role in the maintenance of genomic integrity
      has awarded them a role as the guardians of DNA. Among the tumor suppressors, p53
      is the most studied. The p53 protein has been shown to be a transcription factor
      that recognizes and binds to specific DNA response elements and activates gene
      transcription. Stress triggered by ionizing radiation or other mutagenic events
      leads to p53 phosphorylation and cell-cycle arrest, senescence, or programed cell
      death. The p53 gene is the most frequently mutated gene in cancer. Mutations in
      the DNA-binding domain are classified as class I or class II depending on whether
      substitutions occur in the DNA contact sites or in the protein core,
      respectively. Tumor-associated p53 mutations often lead to the loss of protein
      function, but recent investigations have also indicated gain-of-function
      mutations. The prion-like aggregation of mutant p53 is associated with loss-of
      function, dominant-negative, and gain-of-function effects. In the current review,
      we focused on the most recent insights into the protein structure and function of
      the c-Abl and p53 proteins that will provide us guidance to understand the loss
      and gain of function of these misfolded tumor-associated proteins. 

PMID- 25973401
TI  - Dental caries and their treatment needs in 3-5 year old preschool children in a
      rural district of India.
AB  - BACKGROUND: Dental problems in the preschool children are neglected by their
      parents as the deciduous teeth are going to shed off, and hence considered to be
      of no importance and more of economic burden if attended to them. AIMS: This
      study was to determine the caries prevalence in preschool children (3-5-year-old)
      of rural Moradabad district, to analyze the specific pattern of dental caries
      experience in this population and to assess the treatment needs among them.
      MATERIAL AND METHODS: Children within the age group of 3-5 years attending
      Anganwadi centers of rural Moradabad district were included in the study. Caries
      diagnosis was based on decayed, extracted, filled surface (defs) and the
      treatment needs were recorded using World Health Organization (WHO) oral health
      assessment form 1997. RESULTS: Out of 1,500 children examined, 48.7% males and
      52.6% females did not require any treatment. The mean decayed, extracted, filled
      teeth (deft) value was found to be significantly high in 5-year-old participants
      when compared to 3-year-old participants (P < 0.01). Majority of the children
      required one surface filling followed by two surface fillings, caries arresting
      sealant care, extraction, crown bridge element, pulp care, and space maintainer.
      CONCLUSION: The most common pattern was pit and fissure, then maxillary anterior
      pattern, posterior proximal pattern, and posterior buccal lingual smooth surface
      pattern. The mean deft value was higher in males as compared to females. There is
      a greater need for oral health education among parents and teachers.

PMID- 25973402
TI  - The Predisposing Factors between Dental Caries and Deviations from Normal Weight.
AB  - BACKGROUND: Dental caries and deviations from normal weight are two conditions
      which share several broadly predisposing factors. So it's important to understand
      any relationship between dental state and body weight if either is to be managed
      appropriately. AIMS: The study was done to find out the correlation between body
      mass index (BMI), diet, and dental caries among 12-15-year-old schoolgoing
      children in Panchkula District. MATERIALS AND METHODS: A multistage sample of 12
      15-year-old school children (n = 810) in Panchkula district, Haryana was
      considered. Child demographic details and diet history for 5 days was recorded.
      Data regarding dental caries status was collected using World Health Organization
      (1997) format. BMI was calculated and categorized according to the World Health
      Organization classification system for BMI. The data were subjected to
      statistical analysis using chi-square test and binomial regression developed
      using the Statistical Package for Social Sciences (SPSS) 20.0. RESULTS: The mean
      Decayed Missing Filled Teeth (DMFT) score was found to be 1.72 with decayed,
      missing, and filled teeth to be 1.22, 0.04, and 0.44, respectively. When the
      sample was assessed based on type of diet, it was found that vegetarians had
      higher mean DMFT (1.72) as compared to children having mixed diet. Overweight
      children had highest DMFT (3.21) which was followed by underweight (2.31) and
      obese children (2.23). Binomial regression revealed that females were 1.293 times
      at risk of developing caries as compared to males. Fair and poor Simplified-Oral
      Hygiene Index (OHI-S) showed 3.920 and 4.297 times risk of developing caries as
      compared to good oral hygiene, respectively. Upper high socioeconomic status
      (SES) is at most risk of developing caries. Underweight, overweight, and obese
      are at 2.7, 2.5, and 3 times risk of developing caries as compared to children
      with normal BMI, respectively. CONCLUSION: Dental caries and deviations from
      normal weight are two conditions which share several broadly predisposing factors
      such as diet, SES, lifestyle and other environmental factors.

PMID- 25973405
TI  - Editorial.

PMID- 25973404
TI  - Relationship of resting heart rate and physical activity with insulin sensitivity
      in a population-based survey.
AB  - BACKGROUND: Resting heart rate (RHR) has been identified as an independent risk
      factor for cardiovascular disease and mortality, contributing to atherosclerosis,
      the progression of heart failure, and myocardial ischemia and infarction. This
      study examines the association RHR and physical activity has with insulin
      resistance and insulin secretion in a multiethnic cohort from North Kohala,
      Hawai'i. METHODS: Cross-sectional data from 1,440 participants of Native
      Hawaiian, Japanese, Filipino, Caucasian, and mixed ethnic ancestries were
      analyzed for the study to include anthropometric measurements, and biochemical
      markers. Body fat was estimated by calculating body mass indices (BMI); body fat
      distribution by waist-hip ratios (WHR); and fasting plasma glucose and insulin
      levels were used to calculate insulin resistance using the Homeostasis Model
      (HOMA-IR). First phase insulin response was estimated using the insulin secretion
      ratio (ISR). Associations were estimated using general linear models (GLM).
      RESULTS: Caucasians had lower mean RHR than all other ethnic groups; there were
      no statistically significant differences between other ethnic groups on mean RHR.
      HOMA-IR was associated with ethnic group, BMI and WHR, PA and RHR, while ISR was
      associated with age, ethnic group and BMI, but none of the primary risk factors.
      Both RHR and physical activity level remained significant for insulin resistance.
      CONCLUSIONS: In a multiethnic cohort from a rural community in Hawai'i, increased
      RHR and a lower level of physical activity were both independently associated
      with increased risk for the development of insulin resistance, suggesting
      cardiovascular fitness may be as important as physical activity in preventing
      insulin resistance.

PMID- 25973406
TI  - Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal
      and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo
      Method.
AB  - BACKGROUND: Gel polymers are considered as new dosimeters for determining
      radiotherapy dose distribution in three dimensions. OBJECTIVE: The ability of a
      new formulation of MAGIC-f polymer gel was assessed by experimental measurement
      and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs)
      in prostate dose distributions under the internal Ir-192 and external 18MV
      radiotherapy practices. METHOD: A Plexiglas phantom was made representing human
      pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were
      synthesized using chemical reduction method. Then, a new formulation of MAGIC-f
      gel was synthesized. The fabricated gel was poured in the tubes located at the
      prostate (with and without the GNPs) and bladder locations of the phantom. The
      phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac
      separately based on common radiotherapy procedures used for prostate cancer.
      After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI
      scanner. The absolute doses at the reference points and isodose curves resulted
      from the experimental measurement of the gels and MC simulations following the
      internal and external radiotherapy practices were compared. RESULTS: The mean
      absorbed doses measured with the gel in the presence of the GNPs in prostate were
      15% and 8 % higher than the corresponding values without the GNPs under the
      internal and external radiation therapies, respectively. MC simulations also
      indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the
      same experimental internal and external radiotherapy practices, respectively.
      CONCLUSION: There was a good agreement between the dose enhancement factors
      (DEFs) estimated with MC simulations and experiment gel measurements due to the
      GNPs. The results indicated that the polymer gel dosimetry method as developed
      and used in this study, can be recommended as a reliable method for investigating
      the DEF of GNPs in internal and external radiotherapy practices.

PMID- 25973403
TI  - Diet, exercise or diet with exercise: comparing the effectiveness of treatment
      options for weight-loss and changes in fitness for adults (18-65 years old) who
      are overfat, or obese; systematic review and meta-analysis.
AB  - There are number of means of methods to alter body composition, and metabolic
      issues, available for the adult who is overfat. The following is a systematic
      review and meta-analysis focused on comparing changes from treatment program for
      adults who are overfat based on analysis of aggregated effect size (ES) of
      inducing changes. So as to determine the relative effectiveness of such protocols
      and intervention plans of choice. This tiered meta-analysis of 66-population
      based studies, and 162-studywise groups, a clear pattern of ES being established
      across and within treatments. First, hypocaloric balance is necessary for
      changing body composition, but the effectiveness for establishing imbalance does
      not equate with the effectiveness for body compositional changes, or any
      biomarkers associated with metabolic issues. With analysis showing that there is
      a necessity to include exercise in combination with diet effectively elicit
      changes in body composition and biomarkers of metabolic issues. More importantly,
      the combination, resistance training (RT) was more effective than endurance
      training (ET) or combination of RT and ET, particularly when progressive training
      volume of 2-to-3 sets for 6-to-10 reps at an intensity of >=75% 1RM, utilizing
      whole body and free-weight exercises, at altering body compositional measures (ES
      of 0.47, 0.30, and 0.40 for loss of BM, FM, and retention of FFM respectively)
      and reducing total cholesterol (ES = 0.85), triglycerides (ES = 0.86) and low
      density lipoproteins (ES = 0.60). Additionally RT was more effective at reducing
      fasting insulin levels (ES = 3.5) than ET or ET and RT. Even though generally
      lower ES than RT, the inclusion of ET was more effective when performed at high
      intensity (e.g. >=70% VO2max or HRmax for 30-minutes 3-4x's/wk), or in an
      interval training style than when utilizing the relatively common prescribed
      method of low-to-moderate (e.g., 50-70% VO2max or HRmax for at least equal time)
      steady state method, ES of 0.35, 0.39, and 0.13 for BM, FM, and FFM respectively.
      Thus indicating that focus of treatment should be on producing a large metabolic
      stress (as induced by RT or high levels of ET) rather than an energetic imbalance
      for adults who are overfat. 

PMID- 25973407
TI  - Effect of tissue composition on dose distribution in electron beam radiotherapy.
AB  - OBJECTIVE: The aim of this study is to evaluate the effect of tissue composition
      on dose distribution in electron beam radiotherapy. METHODS: A Siemens Primus
      linear accelerator and a phantom were simulated using MCNPX Monte Carlo code. In
      a homogeneous cylindrical phantom, six types of soft tissue and three types of
      tissue-equivalent materials were investigated. The tissues included muscle
      (skeletal), adipose tissue, blood (whole), breast tissue, soft tissue (9
      components) and soft tissue (4-component). The tissue-equivalent materials were
      water, A-150 tissue-equivalent plastic and perspex. Electron dose relative to
      dose in 9-component soft tissue at various depths on the beam's central axis was
      determined for 8, 12, and 14 MeV electron energies. RESULTS: The results of
      relative electron dose in various materials relative to dose in 9-component soft
      tissue were reported for 8, 12 and 14 MeV electron beams as tabulated data. While
      differences were observed between dose distributions in various soft tissues and
      tissue-equivalent materials, which vary with the composition of material,
      electron energy and depth in phantom, they can be ignored due to the incorporated
      uncertainties in Monte Carlo calculations. CONCLUSION: Based on the calculations
      performed, differences in dose distributions in various soft tissues and tissue
      equivalent materials are not significant. However, due to the difference in
      composition of various materials, further research in this field with lower
      uncertainties is recommended.

PMID- 25973408
TI  - Accuracy Evaluation of OncentraTM TPS in HDR Brachytherapy of Nasopharynx Cancer
      Using EGSnrc Monte Carlo Code.
AB  - BACKGROUND: HDR brachytherapy is one of the commonest methods of nasopharyngeal
      cancer treatment. In this method, depending on how advanced one tumor is, 2 to 6
      Gy dose as intracavitary brachytherapy is prescribed. Due to high dose rate and
      tumor location, accuracy evaluation of treatment planning system (TPS) is
      particularly important. Common methods used in TPS dosimetry are based on
      computations in a homogeneous phantom. Heterogeneous phantoms, especially patient
      specific voxel phantoms can increase dosimetric accuracy. MATERIALS AND METHODS:
      In this study, using CT images taken from a patient and ctcreate-which is a part
      of the DOSXYZnrc computational code, patient-specific phantom was made. Dose
      distribution was plotted by DOSXYZnrc and compared with TPS one. Also, by
      extracting the voxels absorbed dose in treatment volume, dose-volume histograms
      (DVH) was plotted and compared with OncentraTM TPS DVHs. RESULTS: The results
      from calculations were compared with data from OncentraTM treatment planning
      system and it was observed that TPS calculation predicts lower dose in areas near
      the source, and higher dose in areas far from the source relative to MC code.
      Absorbed dose values in the voxels also showed that TPS reports D90 value is 40%
      higher than the Monte Carlo method. CONCLUSION: Today, most treatment planning
      systems use TG-43 protocol. This protocol may results in errors such as
      neglecting tissue heterogeneity, scattered radiation as well as applicator
      attenuation. Due to these errors, AAPM emphasized departing from TG-43 protocol
      and approaching new brachytherapy protocol TG-186 in which patient-specific
      phantom is used and heterogeneities are affected in dosimetry.

PMID- 25973409
TI  - Evaluation of electron contamination in cancer treatment with megavoltage photon
      beams: monte carlo study.
AB  - BACKGROUND: Megavoltage beams used in radiotherapy are contaminated with
      secondary electrons. Different parts of linac head and air above patient act as a
      source of this contamination. This contamination can increase damage to skin and
      subcutaneous tissue during radiotherapy. Monte Carlo simulation is an accurate
      method for dose calculation in medical dosimetry and has an important role in
      optimization of linac head materials. The aim of this study was to calculate
      electron contamination of Varian linac. MATERIALS AND METHOD: The 6MV photon beam
      of Varian (2100 C/D) linac was simulated by Monte Carlo code, MCNPX, based on its
      company's instructions. The validation was done by comparing the calculated depth
      dose and profiles of simulation with dosimetry measurements in a water phantom
      (error less than 2%). The Percentage Depth Dose (PDDs), profiles and
      contamination electron energy spectrum were calculated for different therapeutic
      field sizes (5*5 to 40*40 cm(2)) for both linacs. RESULTS: The dose of electron
      contamination was observed to rise with increase in field size. The contribution
      of the secondary contamination electrons on the surface dose was 6% for 5*5 cm(2)
      to 27% for 40*40 cm(2), respectively. CONCLUSION: Based on the results, the
      effect of electron contamination on patient surface dose cannot be ignored, so
      the knowledge of the electron contamination is important in clinical dosimetry.
      It must be calculated for each machine and considered in Treatment Planning
      Systems.

PMID- 25973410
TI  - Investigation of Collimator Influential Parameter on SPECT Image Quality: a Monte
      Carlo Study.
AB  - BACKGROUND: Obtaining high quality images in Single Photon Emission Tomography
      (SPECT) device  is the most important goal in nuclear medicine. Because if image
      quality is low, the possibility of making a mistake in diagnosing and treating
      the patient will rise. Studying effective factors in spatial resolution of
      imaging systems is thus deemed to be vital. One of the most important factors in
      SPECT imaging in nuclear medicine is the use of an appropriate collimator for a
      certain radiopharmaceutical feature in order to create the best image as it can
      be effective in the quantity of Full Width at Half Maximum (FWHM) which is the
      main parameter  in spatial resolution. METHOD: In this research, the simulation
      of the detector and collimator of SPECT imaging device, Model HD3 made by Philips
      Co. and the investigation of important factors on the collimator were carried out
      using MCNP-4c code. RESULTS: The results of the experimental measurments and
      simulation calculations revealed a relative difference of less than 5% leading to
      the confirmation of the accuracy of conducted simulation MCNP code calculation.
      CONCLUSION: This is the first essential step in the design and modelling of new
      collimators used for creating high quality images in nuclear medicine.

PMID- 25973411
TI  - Normothermia for pediatric and congenital heart surgery: an expanded horizon.
AB  - Cardiopulmonary bypass (CPB) in pediatric cardiac surgery is generally performed
      with hypothermia, flow reduction and hemodilution. From October 2013 to December
      2014, 55 patients, median age 6 years (range 2 months to 52 years), median weight
      18.5 kg (range 3.2-57 kg), underwent surgery with normothermic high flow CPB in a
      new unit. There were no early or late deaths. Fifty patients (90.9%) were
      extubated within 3 h, 3 (5.5%) within 24 h, and 2 (3.6%) within 48 h. Twenty-four
      patients (43.6%) did not require inotropic support, 31 (56.4%) received dopamine
      or dobutamine: 21 <=5 mcg/kg/min, 8 5-10 mcg/kg/min, and 2 >10 mcg/kg/min. Two
      patients (6.5%) required noradrenaline 0.05-0.1 mcg/kg/min. On arrival to ICU and
      after 3 and 6 h and 8:00 a.m. the next morning, mean lactate levels were 1.9 +/-
      09, 2.0 +/- 1.2, 1.6 +/- 0.8, and 1.4 +/- 0.7 mmol/L (0.6-5.2 mmol/L),
      respectively. From arrival to ICU to 8:00 a.m. the next morning mean urine output
      was 3.8 +/- 1.5 mL/kg/h (0.7-7.6 mL/kg/h), and mean chest drainage was 0.6 +/-
      0.5 mL/kg/h (0.1-2.3 mL/kg/h). Mean ICU and hospital stay were 2.7 +/- 1.4 days
      (2-8 days) and 7.2 +/- 2.2 days (4-15 days), respectively. In conclusion,
      normothermic high flow CPB allows pediatric and congenital heart surgery with
      favorable outcomes even in a new unit. The immediate post-operative period is
      characterized by low requirement for inotropic and respiratory support, low
      lactate production, adequate urine output, minimal drainage from the chest
      drains, short ICU, and hospital stay. 

PMID- 25973412
TI  - Acute myeloid leukemia in infants: biology and treatment.
AB  - Children aged 0-2 years (i.e., infants) with acute myeloid leukemia (AML) are a
      peculiar subgroup of patients in the childhood AML scenario. They present with
      distinctive biological and clinical characteristics, including a high prevalence
      of prognostically unfavorable risk factors and an increased susceptibility to
      therapy-related toxicity. Remarkable improvements have been achieved over the
      last two decades in the treatment of these patients and their outcome is becoming
      superimposable to that of the older age groups. In this review, we will focus on
      peculiarities of this young subgroup of children with AML, describing their
      clinical presentation, the biology of disease, and factors influencing outcome.
      Treatment results and toxicity data reported by major collaborative groups are
      also summarized and compared. 

PMID- 25973413
TI  - A border versus non-border comparison of food environment, poverty, and ethnic
      composition in Texas urban settings.
AB  - PURPOSE: The goal was to examine the relationship between the food environment
      and selected socioeconomic variables and ethnic/racial makeup in the eight
      largest urban settings in Texas so as to gain a better understanding of the
      relationships among Hispanic composition, poverty, and urban foodscapes,
      comparing border to non-border urban environments. METHODS: Census-tract level
      data on (a) socioeconomic factors, like percentage below the poverty line and
      number of households on foodstamps, and (b) ethnic variables, like percent of
      Mexican origin and percent foreign born, were obtained from the U.S. Census. Data
      at the census-tract level on the total number of healthy (e.g., supermarkets) and
      less-healthy (e.g., fast food outlets) food retailers were acquired from the
      CDC's modified retail food environment index (mRFEI). Variation among urban
      settings in terms of the relationship between mRFEI scores and socioeconomic and
      ethnic context was tested using a mixed-effect model, and linear regression was
      used to identify significant factors for each urban location. A jackknife
      variance estimate was used to account for clustering and autocorrelation of
      adjacent census tracts. RESULTS: Average census-tract mRFEI scores exhibited
      comparatively small variation across Texas urban settings, while socioeconomic
      and ethnic factors varied significantly. The only covariates significantly
      associated with mRFEI score were percent foreign born and percent Mexican origin.
      Compared to the highest-population county (Harris, which incorporates most of
      Houston), the only counties that had significantly different mRFEI scores were
      Bexar, which is analogous to San Antonio (2.12 lower), El Paso (2.79 higher), and
      Neuces, which encompasses Corpus Christi (2.90 less). Significant interaction
      effects between mRFEI and percent foreign born (El Paso, Tarrant - Fort Worth,
      Travis - Austin), percent Mexican origin (Hidalgo - McAllen, El Paso, Tarrant,
      Travis), and percent living below the poverty line (El Paso) were observed for
      some urban settings. Percent foreign born and percent Mexican origin tended to be
      positively associated with mRFEI in some locations (Hidalgo, El Paso) and
      negatively associated in others (Tarrant, Travis). DISCUSSION: Findings are
      consistent with other studies that suggest the effects of Hispanic concentration
      on the foodscape may be positive (beneficially healthy) in border urban settings
      and negative in non-border. The evidence implies that the effects of Hispanic
      ethnic composition on the food environment are location-dependent, reflecting the
      unique attributes (e.g., culture, infrastructure, social networks) of specific
      urban settings.

PMID- 25973414
TI  - Difficulties of using single-diseased guidelines to treat patients with multiple
      diseases.

PMID- 25973415
TI  - Effect of mediterranean diet in diabetes control and cardiovascular risk
      modification: a systematic review.
AB  - BACKGROUND: Over the past few years, there has been a worldwide significant
      increase in the incidence of type II diabetes mellitus with both increase in
      morbidity and mortality. Controlling diabetes through life style modifications,
      including diet and exercise has always been the cornerstone in diabetes
      management. Increasing evidence suggests that the Mediterranean diet could be of
      benefit in diseases associated with chronic inflammation, including metabolic
      syndrome, diabetes, obesity as well as atherosclerosis, cancer, pulmonary
      diseases, and cognition disorders As a matter of fact, a number of studies
      addressed the relationship between Mediterranean diet and diabetes control. The
      result of these studies was conflicting. Some were able to elicit a protective
      role, while others showed no added benefit. As a result; we decided to conduct a
      systematic review to have a better understanding of the relationship between
      adherence to Mediterranean diet and diabetes control. METHODS: A systematic
      review was conducted on the effect of Mediterranean diet in diabetes control and
      cardiovascular risk modification as well as the possible mechanism through which
      this diet might exhibit its beneficial role. We did a comprehensive search of
      multiple electronic databases such as Medline, Google Scholars, PubMed, and the
      Cochrane central register data until May 2014. We included cross-sectional,
      prospective, and controlled clinical trials that looked at the associations
      between Mediterranean diet and indices of diabetes control such HbA1c, fasting
      glucose, and homeostasis model assessment, in addition to cardiovascular and
      peripheral vascular outcomes. OUTCOME/CONCLUSION: Most of the studies showed
      favorable effects of Mediterranean diet on glycemic control and CVD, although a
      certain degree of controversy remains regarding some issues, such as obesity.
      Important methodological differences and limitations in the studies make it
      difficult to compare results, thus further longer term studies are needed to
      evaluate the long-term efficacy of the Mediterranean diet along with the
      possibility of explaining its mechanism.

PMID- 25973416
TI  - Integrating novel data streams to support biosurveillance in commercial livestock
      production systems in developed countries: challenges and opportunities.
AB  - Reducing the burden of emerging and endemic infectious diseases on commercial
      livestock production systems will require the development of innovative
      technology platforms that enable information from diverse animal health resources
      to be collected, analyzed, and communicated in near real-time. In this paper, we
      review recent initiatives to leverage data routinely observed by farmers,
      production managers, veterinary practitioners, diagnostic laboratories,
      regulatory officials, and slaughterhouse inspectors for disease surveillance
      purposes. The most commonly identified challenges were (1) the lack of
      standardized systems for recording essential data elements within and between
      surveillance data streams, (2) the additional time required to collect data
      elements that are not routinely recorded by participants, (3) the concern over
      the sharing and use of business sensitive information with regulatory authorities
      and other data analysts, (4) the difficulty in developing sustainable incentives
      to maintain long-term program participation, and (5) the limitations in current
      methods for analyzing and reporting animal health information in a manner that
      facilitates actionable response. With the significant recent advances in
      information science, there are many opportunities to develop more sophisticated
      systems that meet national disease surveillance objectives, while still providing
      participants with valuable tools and feedback to manage routine animal health
      concerns. 

PMID- 25973417
TI  - Research, practice, and policy perspectives on evidence-based programing for
      older adults.

PMID- 25973418
TI  - Biological Risks and Laboratory-Acquired Infections: A Reality That Cannot be
      Ignored in Health Biotechnology.
AB  - Advances and research in biotechnology have applications over a wide range of
      areas, such as microbiology, medicine, the food industry, agriculture,
      genetically modified organisms, and nanotechnology, among others. However,
      research with pathogenic agents, such as virus, parasites, fungi, rickettsia,
      bacterial microorganisms, or genetic modified organisms, has generated concern
      because of their potential biological risk - not only for people, but also for
      the environment due to their unpredictable behavior. In addition, concern for
      biosafety is associated with the emergence of new diseases or re-emergence of
      diseases that were already under control. Biotechnology laboratories require
      biosafety measures designed to protect their staff, the population, and the
      environment, which may be exposed to hazardous organisms and materials.
      Laboratory staff training and education is essential, not only to acquire a good
      understanding about the direct handling of hazardous biological agents but also
      knowledge of the epidemiology, pathogenicity, and human susceptibility to the
      biological materials used in research. Biological risk can be reduced and
      controlled by the correct application of internationally recognized procedures
      such as proper microbiological techniques, proper containment apparatus, adequate
      facilities, protective barriers, and special training and education of laboratory
      workers. To avoid occupational infections, knowledge about standardized
      microbiological procedures and techniques and the use of containment devices,
      facilities, and protective barriers is necessary. Training and education about
      the epidemiology, pathogenicity, and biohazards of the microorganisms involved
      may prevent or decrease the risk. In this way, the scientific community may
      benefit from the lessons learned in the past to anticipate future problems. 

PMID- 25973419
TI  - Cyanobacteria as cell factories to produce plant secondary metabolites.
AB  - Cyanobacteria represent a promising platform for the production of plant
      secondary metabolites. Their capacity to express plant P450 proteins, which have
      essential functions in the biosynthesis of many plant secondary metabolites,
      makes cyanobacteria ideal for this purpose, and their photosynthetic capability
      allows cyanobacteria to grow with simple nutrient inputs. This review summarizes
      the advantages of using cyanobacteria to transgenically produce plant secondary
      metabolites. Some techniques to improve heterologous gene expression in
      cyanobacteria are discussed. 

PMID- 25973421
TI  - Randomized controlled trial comparing primary and staged basilic vein
      transposition.
AB  - OBJECTIVE: It is unclear if brachio-basilic vein fistula should be performed as a
      primary or staged procedure, particularly for smaller basilic veins. Our aim was
      to report on a randomized controlled trial comparing these two techniques.
      METHODS: Sixteen patients with a basilic vein >=2.5 mm were randomized into
      primary transposed brachio-basilic vein (TBBV) fistula (n = 9) and staged TBBV
      fistula (n = 7). Patients with basilic veins enlarged by previous arteriovenous
      fistulas were excluded. Baseline characteristics of the two study groups,
      including vein size, were comparable (median basilic vein diameter 3.5 mm, range
      2.8-4.1 mm). The staged group had a brachio-basilic vein fistula performed first
      followed by the transposition procedure performed at least 6 weeks later to allow
      the basilic vein to enlarge. TBBV fistula maturation at 10 weeks, primary,
      assisted-primary, and secondary patency were the primary outcome measures. Early
      failures were included in the calculation of patency rates. RESULTS: Transposed
      brachio-basilic vein fistula maturation rate after primary procedures (3/9, 33%)
      was lower compared to maturation rate after staged procedures (7/7, 100%, P =
      0.011, Fisher's exact test), which led to premature termination of the trial.
      Time to hemodialysis [median (interquartile range)] of primary and staged
      procedures was 54 (51.5-113.5) days and 97 (93-126) days, respectively (P =
      0.16). One-year primary and assisted-primary patency rates of primary and staged
      procedures were equivalent (44 vs 57%, P = 0.76 and 44 vs 71%, P = 0.29,
      respectively); however, there was a trend toward a better 1-year secondary
      patency after staged procedures (86 vs 44% for primary procedures, P = 0.09).
      CONCLUSIONS: Among candidates for TBBV fistula with a small basilic vein, staged
      transposition achieves higher maturation rates compared to primary procedures, a
      difference reflected in long-term secondary patency. TRIAL REGISTRATION:
      www.ClinicalTrials.gov, identifier NCT01274117.

PMID- 25973420
TI  - A breath of fresh air on the mesenchyme: impact of impaired mesenchymal
      development on the pathogenesis of bronchopulmonary dysplasia.
AB  - The early mouse embryonic lung, with its robust and apparently reproducible
      branching pattern, has always fascinated developmental biologists. They have
      extensively used this embryonic organ to decipher the role of mammalian orthologs
      of Drosophila genes in controlling the process of branching morphogenesis. During
      the early pseudoglandular stage, the embryonic lung is formed mostly of tubes
      that keep on branching. As the branching takes place, progenitor cells located in
      niches are also amplified and progressively differentiate along the proximo
      distal and dorso-ventral axes of the lung. Such elaborate processes require
      coordinated interactions between signaling molecules arising from and acting on
      four functional domains: the epithelium, the endothelium, the mesenchyme, and the
      mesothelium. These interactions, quite well characterized in a relatively simple
      lung tubular structure remain elusive in the successive developmental and
      postnatal phases of lung development. In particular, a better understanding of
      the process underlying the formation of secondary septa, key structural units
      characteristic of the alveologenesis phase, is still missing. This structure is
      critical for the formation of a mature lung as it allows the subdivision of
      saccules in the early neonatal lung into alveoli, thereby considerably expanding
      the respiratory surface. Interruption of alveologenesis in preterm neonates
      underlies the pathogenesis of chronic neonatal lung disease known as
      bronchopulmonary dysplasia. De novo formation of secondary septae appears also to
      be the limiting factor for lung regeneration in human patients with emphysema. In
      this review, we will therefore focus on what is known in terms of interactions
      between the different lung compartments and discuss the current understanding of
      mesenchymal cell lineage formation in the lung, focusing on secondary septae
      formation. 

PMID- 25973423
TI  - Complications following Tension-Free Vaginal Tapes: Accurate Diagnosis and
      Complications Management.
AB  - The sling procedures are the gold standard for SUI treatment. They are highly
      effective but not free from complications. The most common adverse effect for the
      surgery with the implant insertion is: overactive bladder occurring de novo after
      the surgery, voiding dysfunctions, urine retention, and unsatisfactory treatment
      outcome. The most important question that arises after 20 years of sling
      procedures is how to manage the complications and what can be offered to
      complicated patients. The above review summarises the ultrasound findings in
      complicated cases and shows the scheme of management of the clinical problems
      concerning the tape location in suburethral region. 

PMID- 25973422
TI  - The influence of metabolic factors for nonalcoholic Fatty liver disease in women.
AB  - BACKGROUND/AIMS: Women after menopause have increased insulin resistance and
      visceral fat, which may increase the prevalence of nonalcoholic fatty liver
      disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly
      defined. In this study, we aimed to determine the risk factors for NAFLD in
      women. METHODS: A retrospective cohort study was conducted. Women who underwent
      abdominal ultrasonography and blood sampling for routine health check-ups were
      recruited. RESULTS: Among 1,423 subjects, 695 women (48.9%) were in a menopausal
      state. The prevalence of NAFLD was higher in postmenopausal women than in
      premenopausal women (27.2% versus 14.4%, P < 0.001). In premenopausal women, low
      HDL-cholesterol, central obesity, and homeostasis model assessment-estimated
      insulin resistance showed a significant association with the increased risk of
      NAFLD in multivariate analysis. In postmenopausal women, the presence of
      diabetes, triglyceridemia, and central obesity showed a significant association
      with the risk of NAFLD. The presence of menopause and hormone replacement therapy
      in postmenopausal women were not risk factors for NAFLD. CONCLUSIONS: Our
      findings showed different metabolic factors for NAFLD in pre- and postmenopausal
      women. However, the key issues are the same: central obesity and insulin
      resistance. These results reemphasize the importance of metabolic factors
      irrespective of menopausal status in the pathogenesis of NAFLD in women.

PMID- 25973424
TI  - Integrated analysis of multiscale large-scale biological data for investigating
      human disease.

PMID- 25973425
TI  - Management of Mesh Complications after SUI and POP Repair: Review and Analysis of
      the Current Literature.
AB  - PURPOSE: To evaluate the surgical treatment concepts for the complications
      related to the implantation of mesh material for urogynecological indications.
      MATERIALS AND METHODS: A review of the current literature on PubMed was
      performed. RESULTS: Only retrospective studies were detected. The rate of mesh
      related complications is about 15-25% and mesh erosion is up to 10% for POP and
      SUI repair. Mesh explantation is necessary in about 1-2% of patients due to
      complications. The initial approach appears to be an early surgical treatment
      with partial or complete mesh resection. Vaginal and endoscopic access for mesh
      resection is favored. Prior to recurrent surgeries, a careful examination and
      planning for the operation strategy are crucial. CONCLUSIONS: The data on the
      management of mesh complication is scarce. Revisions should be performed by an
      experienced surgeon and a proper follow-up with prospective documentation is
      essential for a good outcome.

PMID- 25973426
TI  - Global convergence on the bioethics of surgical implants.
AB  - The increasing globalization of mankind with pluralistic belief systems
      necessitates physicians by virtue of their profession to partner with bioethics
      for soundly applying emerging knowledge and technologies for the best use of the
      patient. A subfield within medicine in which this need is acutely felt is that of
      surgical implants. Within this subfield such recent promising ethics and medicine
      partnerships include the International Tissue Engineering Research Association
      and UNESCO Chair in Bioethics and Human Rights' International Code of Ethics. In
      this paper, we provide an overview of the emerging human rights framework from
      bioethics and international law, discussion of key framework principles, their
      application to the current surgical challenge of implantation of surgical mesh
      for prolapse, and conclusions and recommendations. Such discussions are meant to
      facilitate true quality improvement in patient care by ensuring the exciting
      technologies and medical practices emerging new daily are accompanied by an equal
      commitment of physicians to ethically provide their services for the chief end of
      the patient's good. 

PMID- 25973427
TI  - High structural stability of textile implants prevents pore collapse and
      preserves effective porosity at strain.
AB  - Reinforcement of tissues by use of textiles is encouraged by the reduced rate of
      recurrent tissue dehiscence but for the price of an inflammatory and fibrotic
      tissue reaction to the implant. The latter mainly is affected by the size of the
      pores, whereas only sufficiently large pores are effective in preventing a
      complete scar entrapment. Comparing two different sling implants (TVT and SIS),
      which are used for the treatment of urinary incontinence, we can demonstrate that
      the measurement of the effective porosity reveals considerable differences in the
      textile construction. Furthermore the changes of porosity after application of a
      tensile load can indicate a structural instability, favouring pore collapse at
      stress and questioning the use for purposes that are not "tension-free." 

PMID- 25973428
TI  - Animal models of diabetes and metabolic disease 2014.

PMID- 25973430
TI  - Modulation of Th1/Th2 immune responses by killed Propionibacterium acnes and its
      soluble polysaccharide fraction in a type I hypersensitivity murine model:
      induction of different activation status of antigen-presenting cells.
AB  - Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present
      in normal human skin microbiota, which exerts important immunomodulatory effects,
      when used as heat- or phenol-killed suspensions. We previously demonstrated that
      heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the
      bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin
      (OVA) in an immediate hypersensitivity model, depending on the treatment
      protocol. Herein, we investigated the mechanisms responsible for these effects,
      using the same model and focusing on the activation status of antigen-presenting
      cells (APCs). We verified that higher numbers of APCs expressing costimulatory
      molecules and higher expression levels of these molecules are probably related to
      potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher
      expression of toll-like receptors (TLRs) seems to be related to Th2 suppression.
      In vitro cytokines production in cocultures of dendritic cells and T lymphocytes
      indicated that P. acnes and PS seem to perform their effects by acting directly
      on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating
      the expression of costimulatory molecules and TLRs, and these differently
      activated APCs drive distinct T helper patterns to OVA in our model. 

PMID- 25973429
TI  - Updating experimental models of diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by
      alterations in structure and contractility of the myocardium. This pathology is
      initiated by changes in energy substrates and occurs in the absence of
      atherothrombosis, hypertension, or other cardiomyopathies. Inflammation,
      hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been
      studied in numerous diabetic experimental models in animals, mostly rodents. Type
      I and type II diabetes were induced by genetic manipulation, pancreatic toxins,
      and fat and sweet diets, and animals recapitulate the main features of human
      diabetes and related cardiomyopathy. In this review we update and discuss the
      main experimental models of diabetic cardiomyopathy, analysing the associated
      metabolic, structural, and functional abnormalities, and including current tools
      for detection of these responses. Also, novel experimental models based on
      genetic modifications of specific related genes have been discussed. The study of
      specific pathways or factors responsible for cardiac failures may be useful to
      design new pharmacological strategies for diabetic patients. 

PMID- 25973431
TI  - Modulation of immune response by organophosphorus pesticides: fishes as a
      potential model in immunotoxicology.
AB  - Immune response is modulated by different substances that are present in the
      environment. Nevertheless, some of these may cause an immunotoxic effect. In this
      paper, the effect of organophosphorus pesticides (frequent substances spilled in
      aquatic ecosystems) on the immune system of fishes and in immunotoxicology is
      reviewed. Furthermore, some cellular and molecular mechanisms that might be
      involved in immunoregulation mechanisms of organophosphorus pesticides are
      discussed. 

PMID- 25973432
TI  - Impact of inflammatory cytokine gene polymorphisms on developing acute graft
      versus-host disease in children undergoing allogeneic hematopoietic stem cell
      transplantation.
AB  - Single nucleotide polymorphisms (SNPs) in gene encoding pro- and anti
      inflammatory factors have been associated with the occurrence of aGvHD. We
      retrospectively tested a wide panel of 38 polymorphisms in 19 immunoregulatory
      genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were
      significantly associated with the development of aGvHD. A significant association
      was found between aGvHD grades II-IV and SNPs of donor IL10-1082GG, and Fas-670CC
      + CT and recipient IL18-607 TT + TG genotype. aGvHD grades III-IV resulted
      associated with donor IL10-1082GG, Fas-670CC + CT, and TLR4-3612TT as well as the
      use of peripheral CD34+ cells as stem cell source. The multivariate analysis
      confirmed the association between donor IL10-1082GG and Fas-670CC + CT and aGvHD
      grades II-IV and between donor IL10-1082GG and TLR4-3612TT and aGvHD grades III
      IV. In conclusion we found an association between IL10, FAS, and TLR4 in the
      donor and IL18 in the recipient and an increased risk of developing aGvHD in
      transplanted children. Knowledge of the SNPs of cytokine genes associated with
      aGvHD represents a useful tool for an integrated pretransplantation risk
      assessment and could guide the physicians to an optimal and more accurate HSCT
      planning. 

PMID- 25973433
TI  - Vitamin D and atopic dermatitis in childhood.
AB  - Vitamin D features immunomodulatory effects on both the innate and adaptive
      immune systems, which may explain the growing evidence connecting vitamin D to
      allergic diseases. A wealth of studies describing a beneficial effect of vitamin
      D on atopic dermatitis (AD) prevalence and severity are known. However,
      observations linking high vitamin D levels to an increased risk of developing AD
      have also been published, effectively creating a controversy. In this paper, we
      review the existing literature on the association between AD and vitamin D
      levels, focusing on childhood. As of today, the role of vitamin D in AD is far
      from clear; additional studies are particularly needed in order to confirm the
      promising therapeutic role of vitamin D supplementation in childhood AD. 

PMID- 25973434
TI  - The effects of bromocriptine on preventing postpartum flare in systemic lupus
      erythematosus patients from South China.
AB  - OBJECTIVE: Prolactin plays an important role on the disease flare of postpartum
      SLE patients. 76 pregnant SLE patients were enrolled in this study to evaluate
      the efficacy of bromocriptine (an inhibitor of prolactin secretion) on preventing
      the postpartum disease relapse. METHODS: Patients were randomly divided into the
      treatment group (bromocriptine, 2.5 mg oral, twice a day for 14 days after
      delivery) and the control group. All the patients were followed up for 12 months.
      Clinical features were recorded every 4 weeks. Serum prolactin and estradiol
      levels were measured at the second week and the second month after delivery. The
      endpoint of the study was disease relapse and defined when SLEDAI score increased
      by >=3 points from the antenatal baseline. RESULTS: (1) Serum levels of prolactin
      and estradiol decreased significantly in bromocriptine treatment group at the
      second week (P < 0.001) and second month (P < 0.05) after delivery compared to
      control group. (2) The relapse rate of the treatment group was lower than the
      control group (chi (2) = 4.68, P = 0.0305). CONCLUSIONS: Two weeks of oral
      bromocriptine treatment in postpartum SLE patients may relieve the disease from
      hyperprolactinemia and hyperestrogenemia and may be beneficial in preventing the
      patients from disease relapse.

PMID- 25973435
TI  - Gender-related effects of sex steroids on histamine release and FcepsilonRI
      expression in rat peritoneal mast cells.
AB  - Mast cells (MCs) are versatile effector and regulatory cells in various
      physiologic, immunologic, and pathologic processes. In addition to the well
      characterized IgE/FcepsilonRI-mediated degranulation, a variety of biological
      substances can induce MCs activation and release of their granule content. Sex
      steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs
      activation. Most published studies have been conducted on MCs lines or freshly
      isolated peritoneal and bone marrow-derived MC without addressing gender impact
      on MC response. Our goal was to investigate if the effect of estradiol,
      progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ
      depending on whether female or male rats are used as MCs donors. Our results
      demonstrated that effect of sex steroids on MCs histamine release is dose- and
      gender-dependent and can be direct, synergistic, or inhibitory depending on
      whether hormones are used alone or to pretreat MCs followed by substance P
      stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not
      have effect on the MC expression of the IgE high affinity receptor, FcepsilonRI,
      no matter female or male rats were used. In conclusion, MCs degranulation is
      modulated by sex hormones in a gender-selective fashion, with MC from females
      being more susceptible than MC from males to the effects of sex steroids. 

PMID- 25973437
TI  - Inhibins tune the thymocyte selection process by regulating thymic stromal cell
      differentiation.
AB  - Inhibins and Activins are members of the TGF-beta superfamily that regulate the
      differentiation of several cell types. These ligands were initially identified as
      hormones that regulate the hypothalamus-pituitary-gonadal axis; however,
      increasing evidence has demonstrated that they are key regulators in the immune
      system. We have previously demonstrated that Inhibins are the main Activin
      ligands expressed in the murine thymus and that they regulate thymocyte
      differentiation, promoting the DN3-DN4 transition and the selection of SP
      thymocytes. As Inhibins are mainly produced by thymic stromal cells, which also
      express Activin receptors and Smad proteins, we hypothesized that Inhibins might
      play a role in stromal cell differentiation and function. Here, we demonstrate
      that, in the absence of Inhibins, thymic conventional dendritic cells display
      reduced levels of MHC Class II (MHCII) and CD86. In addition, the ratio between
      cTECs and mTECs was affected, indicating that mTEC differentiation was favoured
      and cTEC diminished in the absence of Inhibins. These changes appeared to impact
      thymocyte selection leading to a decreased selection of CD4SP thymocytes and
      increased generation of natural regulatory T cells. These findings demonstrate
      that Inhibins tune the T cell selection process by regulating both thymocyte and
      stromal cell differentiation. 

PMID- 25973438
TI  - Epigenetic control of interferon-gamma expression in CD8 T cells.
AB  - Interferon- (IFN-) gamma is an essential cytokine for immunity against
      intracellular pathogens and cancer. IFN-gamma expression by CD4 T lymphocytes is
      observed only after T helper (Th) 1 differentiation and there are several studies
      about the molecular mechanisms that control Ifng expression in these cells.
      However, naive CD8 T lymphocytes do not produce large amounts of IFN-gamma, but
      after TCR stimulation there is a progressive acquisition of IFN-gamma expression
      during differentiation into cytotoxic T lymphocytes (CTL) and memory cells, which
      are capable of producing high levels of this cytokine. Differential gene
      expression can be regulated from the selective action of transcriptional factors
      and also from epigenetic mechanisms, such as DNA CpG methylation or
      posttranslational histone modifications. Recently it has been recognized that
      epigenetic modification is an integral part of CD8 lymphocyte differentiation.
      This review will focus on the chromatin status of Ifng promoter in CD8 T cells
      and possible influences of epigenetic modifications in Ifng gene and conserved
      noncoding sequences (CNSs) in regulation of IFN-gamma production by CD8 T
      lymphocytes. 

PMID- 25973436
TI  - The danger model approach to the pathogenesis of the rheumatic diseases.
AB  - The danger model was proposed by Polly Matzinger as complement to the traditional
      self-non-self- (SNS-) model to explain the immunoreactivity. The danger model
      proposes a central role of the tissular cells' discomfort as an element to prime
      the immune response processes in opposition to the traditional SNS-model where
      foreignness is a prerequisite. However recent insights in the proteomics of
      diverse tissular cells have revealed that under stressful conditions they have a
      significant potential to initiate, coordinate, and perpetuate autoimmune
      processes, in many cases, ruling over the adaptive immune response cells; this
      ruling potential can also be confirmed by observations in several genetically
      manipulated animal models. Here, we review the pathogenesis of rheumatic diseases
      such as systemic lupus erythematous, rheumatoid arthritis, spondyloarthritis
      including ankylosing spondylitis, psoriasis, and Crohn's disease and provide
      realistic approaches based on the logic of the danger model. We assume that
      tissular dysfunction is a prerequisite for chronic autoimmunity and propose two
      genetically conferred hypothetical roles for the tissular cells causing the
      disease: (A) the Impaired cell and (B) the paranoid cell. Both roles are not
      mutually exclusive. Some examples in human disease and in animal models are
      provided based on current evidence. 

PMID- 25973439
TI  - The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor,
      on circulating levels of inflammatory biomarkers in patients with psoriatic
      arthritis: substudy results from a phase III, randomized, placebo-controlled
      trial (PALACE 1).
AB  - Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness
      (versus placebo) for treatment of active psoriatic arthritis in the psoriatic
      arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical
      trial program. Pharmacodynamic effects of apremilast on plasma biomarkers
      associated with inflammation were evaluated in a PALACE 1 substudy. Of 504
      patients randomized in PALACE 1, 150 (placebo: n = 51; apremilast 20 mg BID: n =
      51; apremilast 30 mg BID: n = 48) provided peripheral blood plasma samples for
      analysis in a multiplexed cytometric bead array assay measuring 47 proteins
      associated with systemic inflammatory immune responses. Association between
      biomarker levels and achievement of 20% improvement from baseline in modified
      American College of Rheumatology (ACR20) response criteria was assessed by
      logistic regression. At Week 24, IL-8, TNF-alpha, IL-6, MIP-1beta, MCP-1, and
      ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30
      mg BID versus placebo. ACR20 response correlated with change in TNF-alpha level
      with both apremilast doses. At Week 40, IL-17, IL-23, IL-6, and ferritin were
      significantly decreased and IL-10 and IL-1 receptor antagonists significantly
      increased with apremilast 30 mg BID versus placebo. In patients with active
      psoriatic arthritis, apremilast reduced circulating levels of Th1 and Th17
      proinflammatory mediators and increased anti-inflammatory mediators.

PMID- 25973440
TI  - Lactobacillus acidophilus suppresses colitis-associated activation of the IL
      23/Th17 axis.
AB  - The aim of this paper is to determine the modulatory effects of Lactobacillus
      acidophilus on the IL-23/Th17 immune axis in experimental colitis. DSS-induced
      mouse models of UC were to be saline, hormones, and different concentrations of
      Lactobacillus acidophilus intervention. The expression of interleukin- (IL-) 17,
      tumor necrosis factor alpha (TNFalpha), IL-23, transforming growth factor beta1
      (TGFbeta1), signal transducer and activator of transcription 3 (STAT3), and
      phosphorylated (p)-STAT3 was examined by RT-PCR, Western blotting, and
      immunohistochemical analysis. And the results showed that administration of L.
      acidophilus suppressed Th17 cell-mediated secretion of proinflammatory cytokine
      IL-17 through downregulation of IL-23 and TGFbeta1 expression and downstream
      phosphorylation of p-STAT3. 

PMID- 25973441
TI  - Assessment of physicochemical properties of rituximab related to its
      immunomodulatory activity.
AB  - Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20
      positive B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid
      arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It
      binds specifically to the CD20 antigen expressed on pre-B and consequently on
      mature B-lymphocytes of both normal and malignant cells, inhibiting their
      proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory
      activity of rituximab is closely related to critical quality attributes that
      characterize its chemical composition and spatial configuration, which determine
      the recognition of CD20 and the binding to receptors or factors involved in its
      effector functions, while regulating the potential immunogenic response. Herein,
      we present a physicochemical and biological characterization followed by a
      pharmacodynamics and immunogenicity study to demonstrate comparability between
      two products containing rituximab. The physicochemical and biological
      characterization revealed that both products fit within the same response
      intervals exhibiting the same degree of variability. With regard to clinical
      response, both products depleted CD20+ B-cells until posttreatment recovery and
      no meaningful differences were found in their pharmacodynamic profiles. The
      evaluation of anti-chimeric antibodies did not show differential immunogenicity
      among products. Overall, these data confirm that similarity of critical quality
      attributes results in a comparable immunomodulatory activity. 

PMID- 25973442
TI  - Control of white spot lesion adjacent to orthodontic bracket with use of fluoride
      varnish or chlorhexidine gel.
AB  - The aims of this study were to compare the effectiveness of fluoride varnish and
      chlorhexidine gel in controlling white spot lesions (WSLs) adjacent to
      orthodontic brackets and to compare the ability of Quantitative Light-Induced
      Fluorescence (QLF) to measure mineral uptake with that of transverse
      microradiography (TMR). Thirty premolars with artificially induced WSLs were
      randomly assigned to three groups: (1) two applications of 5% NaF-varnish (F),
      with one-week interval, (2) two applications of 2% chlorhexidine gel (CHX), with
      one-week interval, and (3) control (CO), no treatment. QLF was used to measure
      changes in fluorescence before and after caries induction, 1 week after each
      application and 1, 2, and 3 months after the last application of F or CHX. TMR
      was performed to quantify lesion depth and mineral content after caries induction
      to evaluate the effects of F, CHX, and CO 3 months after the last application of
      agents. The data were analyzed by repeated measures ANOVA and Tukey's test. All
      treatments increased the mineral content during the experimental period; however,
      F induced faster remineralization than CHX. The correlation between QLF and TMR
      was significantly moderate. Two applications of fluoride varnish or 2%
      chlorhexidine gel at one-week intervals were effective in controlling WSLs. 

PMID- 25973444
TI  - Partial storage optimization and load control strategy of cloud data centers.
AB  - We present a novel approach to solve the cloud storage issues and provide a fast
      load balancing algorithm. Our approach is based on partitioning and concurrent
      dual direction download of the files from multiple cloud nodes. Partitions of the
      files are saved on the cloud rather than the full files, which provide a good
      optimization to the cloud storage usage. Only partial replication is used in this
      algorithm to ensure the reliability and availability of the data. Our focus is to
      improve the performance and optimize the storage usage by providing the DaaS on
      the cloud. This algorithm solves the problem of having to fully replicate large
      data sets, which uses up a lot of precious space on the cloud nodes. Reducing the
      space needed will help in reducing the cost of providing such space. Moreover,
      performance is also increased since multiple cloud servers will collaborate to
      provide the data to the cloud clients in a faster manner. 

PMID- 25973445
TI  - Influence Function Learning in Information Diffusion Networks.
AB  - Can we learn the influence of a set of people in a social network from cascades
      of information diffusion? This question is often addressed by a two-stage
      approach: first learn a diffusion model, and then calculate the influence based
      on the learned model. Thus, the success of this approach relies heavily on the
      correctness of the diffusion model which is hard to verify for real world data.
      In this paper, we exploit the insight that the influence functions in many
      diffusion models are coverage functions, and propose a novel parameterization of
      such functions using a convex combination of random basis functions. Moreover, we
      propose an efficient maximum likelihood based algorithm to learn such functions
      directly from cascade data, and hence bypass the need to specify a particular
      diffusion model in advance. We provide both theoretical and empirical analysis
      for our approach, showing that the proposed approach can provably learn the
      influence function with low sample complexity, be robust to the unknown diffusion
      models, and significantly outperform existing approaches in both synthetic and
      real world data.

PMID- 25973443
TI  - The effects of tempol on cyclophosphamide-induced oxidative stress in rat
      micturition reflexes.
AB  - We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in
      oxidative stress and contributes to urinary bladder dysfunction. We determined
      (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive
      oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators,
      neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and
      adenosine triphosphate (ATP) that contribute to the inflammatory process in the
      urinary tract and (2) the functional role of oxidative stress in urinary bladder
      dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with
      conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats,
      ROS/RNS and 3-NT significantly (P <= 0.01) increased in urinary bladder. CYP
      treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and
      cystometric fluid. In CYP-treated rats, Tempol significantly (P <= 0.01)
      increased bladder capacity and reduced voiding frequency compared to CYP-treated
      rats without Tempol. Tempol significantly (P <= 0.01) reduced ATP expression, 3
      NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These
      studies demonstrate that reducing oxidative stress in CYP-induced cystitis
      improves urinary bladder function and reduces markers of oxidative stress and
      inflammation.

PMID- 25973446
TI  - Analysis of Online Social Networks to Understand Information Sharing Behaviors
      Through Social Cognitive Theory.
AB  - Analyzing the contents of online social networks is an effective process for
      monitoring and understanding peoples' behaviors. Since the nature of conversation
      and information propagation is similar to traditional conversation and learning,
      one of the popular socio-cognitive methods, social cognitive theory was applied
      to online social networks to. Two major news topics about colon cancer were
      chosen to monitor traffic of Twitter messages. The activity of "leaders" on the
      issue (i.e., news companies or people will prior Twitter activity on topics
      related to colon cancer) was monitored. In addition, the activity of "followers",
      people who never discussed the topics before, but replied to the discussions was
      also monitored. Topics that produce tangible benefits such as positive outcomes
      from appropriate preventive actions received dramatically more attention and
      online social media traffic. Such characteristics can be explained with social
      cognitive theory and thus present opportunities for effective health campaigns.

PMID- 25973447
TI  - What to do after basal insulin: 3 Tx strategies for type 2 diabetes.
AB  - These strategies can help you optimize glucose control in your patient with type
      2 diabetes when basal insulin alone isn't sufficient. 

PMID- 25973448
TI  - Prurigo nodularis: Picking the right treatment.
AB  - Most patients with localized nodules should receive topical treatment first. But
      disappointing results or specific findings described here could necessitate
      additional or alternative options. 

PMID- 25973449
TI  - Headache . fatigue . blurred vision . Dx?
AB  - One month after moving into her mother's apartment, a 27-year-old woman sought
      care at our clinic for fatigue, headache, blurred vision, nausea, and morning
      vomiting. She had weakness and difficulty sleeping, but denied any fever, rashes,
      neck stiffness, recent travel, trauma, or tobacco or illicit drug use. She did,
      however, have a 6-year history of migraines. 

PMID- 25973450
TI  - Nodules on nose and tattoos.
AB  - Our patient sought treatment for the nodules on his nose, but the nodules on his
      tattoos proved particularly helpful in making the diagnosis. 

PMID- 25973451
TI  - Clinical Inquiry: What therapies alleviate symptoms of polycystic ovary syndrome?
AB  - Women with PCOS who are not seeking pregnancy commonly have symptoms such as
      excessive weight, hirsutism, and menstrual irregularities. This review focuses on
      interventions to manage those symptoms. 

PMID- 25973452
TI  - Clinical Inquiry: Does primary nocturnal enuresis affect childrens' self-esteem?
AB  - Children with primary nocturnal enuresis often, but not always, score about 10%
      lower on standardized rating scales for self-esteem, or scores for symptoms
      similar to low self-esteem (sadness, anxiety, social fears, distress) than
      children without enuresis. 

PMID- 25973453
TI  - CBT is worthwhile--but are we making use of it?

PMID- 25973454
TI  - When to recommend cognitive behavioral therapy.
AB  - Consider CBT for patients who you suspect have anxiety or trauma-related
      disorders. The benefits of this short-term, goal-oriented approach are detailed
      in this review and in the accompanying evidence-based table. 

PMID- 25973455
TI  - PURLs: Consider these medications to help patients stay sober.
AB  - Naltrexone can help prevent relapse in recently detoxified patients with alcohol
      use disorder. The evidence for acamprosate is not quite as strong. 

PMID- 25973456
TI  - Clinical Inquiry: Do statins increase the risk of developing diabetes?
AB  - Statin therapy produces a small increase in the incidence of diabetes: one
      additional case per 255 patients taking statins over 4 years. 

PMID- 25973457
TI  - Anxiety tied to fear of falling . fatigue . difficulty concentrating . Dx?
AB  - A 21-year-old college student was referred to us by the counseling center at our
      university for a psychiatric evaluation after 11 psychotherapy sessions over 3
      months had failed to reduce her feelings of anxiety and panic. 

PMID- 25973458
TI  - EAPCI Focus on the Interventional   Cardiology Working Group of   The Netherlands
      Society of   Cardiology (NVVC).

PMID- 25973459
TI  - Results and complications of silicone frontalis sling surgery for ptosis.
AB  - PURPOSE: Frontalis suspension is the treatment of choice for severe
      blepharoptosis with poor levator function. Several materials are available for
      this purpose. Autologous fascia lata is considered best among naturally occurring
      materials; however, it may not be possible to harvest fascia lata in young
      children. Among various synthetic materials, silicone has been used frequently
      and has given good results. METHODS: This is a retrospective analysis of patients
      operated on from September 2008 to August 2013. All of these patients underwent
      silicone rod frontalis suspension for severe blepharoptosis with poor levator
      function and completed a minimum of 6 months of follow-up. RESULTS: There were 38
      eyes of 25 patients with ages ranging from 3 to 21 years (average: 10.68 +/- 6.26
      years). Of these 25 patients, 10 had blepharophimosis syndrome, 10 had congenital
      ptosis, 3 had third nerve palsy, 1 had double elevator palsy, and 1 had post
      levator resection. Good cosmetic correction was achieved in 34 eyes (89.4%) after
      a mean follow-up of 18 months (range: 6 to 60 months). Complications observed
      included significant eyelid lag and lagophthalmos (5 eyes), undercorrection (4
      eyes), suture granuloma (3 eyes), sling exposure at forehead incision (3 eyes),
      bilateral chronic eyelid edema (1 patient), and late recurrence of ptosis (1
      eye). CONCLUSIONS: Silicone is a safe material for frontalis suspension in
      patients with severe ptosis; however, recurrence, granuloma formation, sling
      exposure, and chronic inflammation can occur with use of silicone rod.

PMID- 25973460
TI  - John S. Waugh (1929-2014).

PMID- 25973461
TI  - Abstracts of the 2014 World Forum on Biology, May 31-June 4, Savannah, Georgia.

PMID- 25973462
TI  - Cystic fibrosis frequently asked questions.

PMID- 25973463
TI  - [Internet and interactions with our activities].

PMID- 25973464
TI  - [Professional association -- what you should consider when designing partnership
      contracts].

PMID- 25973465
TI  - [Communications -- conflicts within the team and how to handle them].

PMID- 25973466
TI  - [Editorial bulletin for Issue 3].

PMID- 25973467
TI  - Abstracts of the ASGCT 17th Annual Meeting, May 21-24, 2014, Washington, DC.

PMID- 25973468
TI  - Reversible control of nanoparticle functionalization and physicochemical
      properties by dynamic covalent exchange.
AB  - Existing methods for the covalent functionalization of nanoparticles rely on
      kinetically controlled reactions, and largely lack the sophistication of the
      preeminent oligonucleotide-based noncovalent strategies. Here we report the
      application of dynamic covalent chemistry for the reversible modification of
      nanoparticle (NP) surface functionality, combining the benefits of non
      biomolecular covalent chemistry with the favorable features of equilibrium
      processes. A homogeneous monolayer of nanoparticle-bound hydrazones can undergo
      quantitative dynamic covalent exchange. The pseudomolecular nature of the NP
      system allows for the in situ characterization of surface-bound species, and real
      time tracking of the exchange reactions. Furthermore, dynamic covalent exchange
      offers a simple approach for reversibly switching-and subtly tuning-NP properties
      such as solvophilicity.

PMID- 25973469
TI  - Cross sectional imaging of metal-on-metal hip arthroplasties. Author reply.

PMID- 25973470
TI  - No clinical benefit of gender-specific total knee arthroplasty: A systematic
      review and meta-analysis of 6 randomized controlled trials. Author reply.

PMID- 25973471
TI  - Comparing EMG amplitude patterns of responses during dynamic exercise: polynomial
      vs log-transformed regression.
AB  - The purposes of this study were to determine if (a) the log-transformed model can
      be applied to dynamic exercise and (b) the slope and y-intercept terms can
      provide additional information above and beyond the polynomial regression
      analyses. Eleven physically active individuals performed incremental cycle
      ergometry on a single occasion. Electromyographic electrodes were placed on the
      three superficial quadriceps muscles to record muscle activation during the
      exercise test. The patterns of responses for electromyographic amplitude vs power
      output were analyzed with polynomial and log-transformed regression models. The
      results of the polynomial regression for the composite data indicated that the
      best-fit model for the vastus lateralis muscle was linear (R(2) = 0.648, P <
      0.0001), whereas the best-fit model for the rectus femoris (R(2) = 0.346, P =
      0.013) and vastus medialis (R(2) = 0.764,P = 0.020) muscles was quadratic. One
      way repeated measures analyses indicated no significant differences(P > 0.05)
      across the three superficial quadriceps muscles for the slope and y-intercept
      terms. These findings suggest that the log-transformed model may be a more
      versatile statistical approach to examining neuromuscular responses during
      dynamic exercise.

PMID- 25973472
TI  - Antiproliferative effect of linalool on RPMI 7932 human melanoma cell line:
      ultrastructural studies.
AB  - Linalool, a small monoterpene molecule, is used widely for its flavoring and
      fragrant properties in many cosmetic products. In this work, we investigated the
      antiproliferative effect of two different linalool solutions on RPMI 7932 human
      melanoma and NCTC 2544 normal keratinocites cell lines using the trypan blue
      method. Morphological changes in cells were investigated by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). In addition,
      apoptosis was evaluated using caspase 3-antibody. Linalool showed a selective
      inhibitory effect on the growth of melanoma cells in a concentrationdependent
      manner, inducing several morphological changes, as revealed by SEM and TEM
      analysis. Moreover, the labelling for caspase-3 is abundant in the melanoma cells
      and almost absent in the normal keratinocites cells. The results suggest that
      linalool could be used as drug and/or as model drug for developing potential
      therapeutic agents for melanoma.

PMID- 25973473
TI  - Synthesis of chiral hexasubstituted cyclohexanediol, a key intermediate for the
      synthesis of verticillol, from (+)-dihydrocarvone; attempted cyclization to 12
      membered carbocycle in verticillol using RCM reaction.
AB  - A cyclohexane derivative with three chiral centers, a key intermediate for the
      synthesis of a diterpene verticillol, was prepared starting from (+)
      dihydrocarvone. A further challenge to cyclize to a 12-membered carbocycle was
      attempted, although the products were dimeric derivatives presumably due to an
      undesirable conformation of the substrate.

PMID- 25973475
TI  - Degradation products of rubusoside under acidic conditions.
AB  - A natural sweetener, Rubusoside (1), subjected to extreme pH and temperature
      conditions, resulted in the isolation and structural elucidation of one novel
      rubusoside degradant (7), together with seven known degradants (2-6 and 8-9). ID
      and 2D NMR spectroscopy (1H, 13C, COSY, HSQC-DEPT, HMBC, and NOESY) and mass
      spectral data were used to fully characterize the degradant 7.

PMID- 25973474
TI  - Diterpenoid derivatives of Kenyan Croton sylvaticus.
AB  - Kenyan Croton sylvaticus Hochst. ex Krauss gave four clerodane diterpenoids, the
      new ent-3,13E-clerodadiene-15-formate (1), the known 15-acetoxy-ent-3,13E
      clerodadiene (2), ent-3,13E-clerodadien-15-ol (3) and hardwickiic acid (4), two
      known halimane diterpenoids, penduliflaworosin (5) and crotohalimaneic acid (6)
      and one labdane diterpenoid, labda-13E-ene-8a,15-diol (7). The compounds, when
      tested for their anti-microbial activities against Bacillus subtilis, Xanthomonas
      campestris and Candida albicans, were found to be inactive.

PMID- 25973476
TI  - A novel triterpene from the roots of Paullinia pinnata: 6alpha-(3'-methoxy-4'
      hydroxybenzoyl)-lup-20(29)-ene-3-one.
AB  - Paullinia pinnata L. (Sapindaceae) is an endemic West African plant that is
      extensively used in traditional medicine to treat various diseases. Previous
      phytochemical analysis by various groups led to the isolation of several novel
      lupene-based triterpenene derivatives along with other classes of compounds. As
      part of our continued phytochemical studies on the roots of this plant, we have
      now identified yet another novel triterpene, 6a-(3'-methoxy-4'-hydroxybenzoyl)
      lup-20(29)-ene-3-one. The identification of the compound through comprehensive
      spectroscopic studies is discussed.

PMID- 25973477
TI  - Effects of ursolic acid on contractile activity of gastric smooth muscles.
AB  - Ursolic acid (UA) in concentrations of l x 10(7) mol/L - 5 x 10(5) mol/L induced
      relaxation in gastric smooth muscle (SM) tissues, in a concentration-dependent
      manner. The relaxation did not change membrane potential and slow wave
      contraction patterns. A significant decrease in amplitude and frequency of spike-
      potentials was observed. UA-induced reactivity was removed when SM preparations
      were treated with nifedipine (1 x 10(6) mol/L). Ca2+-induced contractions of the
      depolarized SM preparations (42 mmol/L K+; Ca2+-free Krebs solution) were
      substantially reduced in the presence of UA. It was determined that, in certain
      concentrations, UA influenced L - type Ca2+ channels, and reduced the Ca2+
      influx.

PMID- 25973478
TI  - Design, synthesis and biological evaluation of caudatin and its ester derivatives
      as novel antitumor agents.
AB  - A series of caudatin ester derivatives were synthesized and tested for their
      activities against human lung cancer A549, human prostate cancer PC3, human liver
      cancer BEL-7402 and human gastric cancer SGC-7901 cell lines. All the compounds
      showed noticeable activities against the tested tumor cell lines, and the IC50s
      are all lower than that of caudatin. Among them, 5e and 5h are the most potent
      compounds. SAR study implies that introducing either a halogenated acyl group or
      amino aryl group to the C3beta position of caudatin is beneficial to their anti
      viability activities, and the lipophilicity affects the anti-viability activity
      of caudatin derivatives.

PMID- 25973479
TI  - Elucidation of the mass fragmentation pathways of tomatidine and beta1
      hydroxytomatine using orbitrap mass spectrometry.
AB  - Tomatoes, members of the Solanaceae plant family, produce biologically active
      secondary metabolites, including glycoalkaloids, which may have both adverse and
      beneficial biological effects. Using the linear ion trap (LIT) mass spectrometry,
      multi-stage collision induced dissociation (CID) experiments (MSn) were performed
      to elucidate characteristic fragmentation pathways of the glycoalkaloid,
      tomatidine and of beta1-hydroxytomatine. High resolution with high accuracy mass
      analysis using an Orbitrap fourier transform MS with higher-energy collisional
      induced dissociation (HCD) was used to produce mass spectra data across a wide
      spectral range for confirmation of proposed ion structures and formulae.

PMID- 25973480
TI  - Alkaloids from Peumus boldus and their acetylcholinesterase,
      butyrylcholinesterase and prolyl oligopeptidase inhibition activity.
AB  - Eleven isoquinoline alkaloids (1-11) were isolated from dried leaves of Peumus
      boldus Mol. by standard chromatographic methods. The chemical structures were
      elucidated by MS, and 1D and 2D NMR spectroscopic analysis, and by comparison
      with literature data. Compounds isolated in sufficient amount were evaluated for
      their acetylcholinesterase, and butyrylcholinesterase inhibition activity using
      Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was
      used as substrate. Promising butyrylcholinesterase inhibition activities were
      demonstrated by two benzylisoquinoline alkaloids, reticuline (8) and N
      methylcoclaurine (9), with IC50 values of 33.6 +/- 3.0 uM and 15.0 +/- 1.4 uM,
      respectively. Important prolyl oligopeptidase inhibition activities were shown by
      N-methyllaurotetanine (6) and sinoacutine (4) with IC50 values of 135.4 +/- 23.2
      uM and 143.1 +/- 25.4 uM, respectively. Other tested compounds were considered
      inactive.

PMID- 25973481
TI  - Concise synthesis of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine
      starting with bufotenine from Brazilian Anadenanthera ssp..
AB  - Bufotenine (1, 5-hydroxy-N,N-dimethyltryptamine) was isolated from seeds of
      Anadenanthera spp., a tree widespread in the Brazilian cerrado, using an
      efficient acid-base shakeout protocol. The conversion of bufotenine into N,N
      dimethyltryptamine (4) and 5-methoxy-N,N-dimethyltryptamine (5) was accomplished
      through an innovative and short approach featuring the use of novel bufotenine
      aminoborane complex (7). Furthermore, an easy methodology for conversion of
      bufotenine into 5-hydroxy-N,N,N-trimethyltryptamine (6) was well-established.
      This is the first study that highlights bufotenine as a resource for the
      production of N,N-dimethyltryptamines for either pharmacological and
      toxicological investigations or for synthetic purposes.

PMID- 25973482
TI  - A new cytotoxic cytochalasin from the endophytic fungus Trichoderma harzianum.
AB  - The new natural product 4]-hydroxy-deacetyl-18-deoxycytochalasin H (1), together
      with the known deacetyl-18-deoxycytochalasin H (2) and 18-deoxycytochalasin H (3)
      were obtained from the endophytic fungus Trichoderma harzianum isolated from
      leaves of Cola nitida. The structure of the new compound was unambiguously
      determined by 1D and 2D NMR spectroscopy, and by HRESIMS measurements, as well as
      by comparison with the literature. Compounds 1-3 showed potent cytotoxic activity
      against the murine lymphoma (L5178Y) cell line and against human ovarian cancer
      (A2780 sens and A2780 CisR) cell lines (IC50 0.19-6.97 uM). The A2780 cell lines
      included cisplatin-sensitive (sens) and -resistant (R) cells.

PMID- 25973484
TI  - Synthesis of auronol derivatives and their immunostimulating activity.
AB  - The first synthesis of alphitonin-4-O-beta-D-glucopyranoside (1) was described.
      Since, the nitrile group, a strong hydrogen bond acceptor with a significant
      solvation shell, is considered to have capacity comparable to sugar for
      facilitating the cell membrane permeation of the molecules, several alphitonin-4
      O-beta-D-glucopyranoside and maesopsin-4-O-beta-D-glucopyranoside analogues were
      prepared by replacing glucopyranose moieties with acetonitrile groups.
      Immunostimulating activity evaluation on lymphocyte proliferation indicated that
      the compound 7 with an acetonitrile group at OH-4 of alphitonin had a strong
      stimulation effect on lymphocyte proliferation. Interestingly, when tested
      against the normal cell NIH/3T3, 7 had no inhibition even at the concentration of
      100 ug/mL.

PMID- 25973483
TI  - Inhibition of soybean 15-lipoxygenase by naturally occurring acetophenones and
      derricidin.
AB  - Three selected naturally occurring oxyprenylated secondary metabolites, namely 2
      hydroxy4-isopentenyloxyacetophenone (1), 4-geranyloxy-2-hydroxyacetophenone (2),
      4-farnesyloxyacetophenone (3), and derricidin (4) were synthesized and their
      inhibitory potency against soybean 15-lipoxygenase evaluated. Compounds 1 and 4
      showed the most potent inhibitory activity with ICo50 values of 2.5 uM and 0.6
      uM.

PMID- 25973485
TI  - Cytotoxic compounds from endemic Arnebia purpurea.
AB  - Phytochemical studies of the roots and aerial parts of endemic Arnebia purpurea
      S. Erik & H. Sumbul resulted in the isolation and characterization of four
      naphthoquinones [isovalerylalkannin (1), alpha-methyl-n-butanoyl alkannin (2),
      acetylalkannin (3), and alkannin (4)], a triterpene derivative [3-O-acetyl
      oleanolic acid (5)], a steroid [beta-sitosterol (6)], three flavonoid glycosides
      [isorhamnetin-3-O-rutinoside (7), kaempferol-3-O-rutinoside (8), kaempferol 3-O
      (5"-acetyl) apiofuranoside 7-O-rhamnopyranoside (9)] and a phenolic acid
      [rosmarinic acid (10)]. 3-O-Acetyl-oleanolic acid, isorhamnetin-3-O-rutinoside,
      kaempferol-3-O-mrutinoside, and kaempferol 3-O-(5"-acetyl) apiofuranoside 7-O
      rhamnopyranoside are reported from an Arnebia species for the first time.
      Cytotoxic activities on L929 murine fibrosarcoma cell line of the isolated
      compounds were investigated using MTT assay. Naphthoquinones (1-4) showed
      intermediate cytotoxic activity in comparison with the standard, doxorubicin.

PMID- 25973486
TI  - Evaluation of the anti-inflammatory and antioxidative potential of four fern
      species from China intended for use as food supplements.
AB  - Inflammation plays a major role in many diseases, for instance in
      arteriosclerosis, rheumatoid arthritis, autoimmune disorders and cancer. Since
      many plants contain compounds with anti-inflammatory activity, their consumption
      may be able to prevent the development of inflammatory-based diseases. Edible
      ferns are some of the most important wild vegetables in China and have
      traditionally been used both for dietary and therapeutic purposes. In this study
      we investigated the anti-inflammatory and antioxidant potential of fern extracts
      from Matteuccia struthiopteris, Osmundajaponica, Matteuccia orientalis and
      Pteridium aquilinum intended for use as nutraceuticals. Two modes of action were
      investigated: the inhibition of the pro-inflammatory gene expression of
      interleukin-1 beta (IL1-beta) and interleukin-6 (IL6), and the gene expression of
      iNOS by LPS-elicited macrophages. The results showed a decrease of IL1-beta gene
      expression for the five fern extracts. This effect was more pronounced for the
      extracts prepared from the roots of O. japonica (IC50 of 17.8 ug/mL) and the
      young fronds of M orientalis (50.0 ug/mL). Regarding the indirect measurement of
      NO, via iNOS gene expression, an interesting decrease of 50% was obtained with
      the extract of M. orientalis fronds at a low concentration (20 ug/mL) compared
      with P. aquilinum fronds (160 ug/mL) and leaves of O. japonica. The latter showed
      a higher decrease but at a high concentration of extract (160 ug/mL). The five
      fern extracts were also evaluated for their ability to scavenge 2,2-diphenyl-l
      picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS). All fern extracts exhibited antioxidant effects but the
      roots of O. japonica and the fronds of M orientalis were most efficient. The HPLC
      MS analysis of the constituents of the fern extracts confirmed the presence of
      chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, kaempferol and
      apigenin, molecules known to exhibit antiinflammatory and/or antioxidant
      properties.

PMID- 25973487
TI  - The search for antifungals from Amazonian trees: a bio-inspired screening.
AB  - The anti-fungal activity of 60 extracts from 15 tree species in the French Guiana
      rainforest against human and wood-rotting fungi was studied. In this way (+)
      mopanol (1) was isolated from the ethyl acetate extract of Peltogyne sp.
      (Caesalpiniaceae) wood. This work demonstrated that (1) the natural durability of
      wood can indeed guide the search for antifungal agents, (2) that extracts
      selected in this bio-inspired process exhibit a broad spectrum of antifungal
      activity and (3) that the method allows for the isolation of strongly active
      antifungals.

PMID- 25973488
TI  - Structure elucidation and antioxidant activity of the phenolic compounds from
      Rhynchosia suaveolens.
AB  - A new benzophenone, 2-hydroxy-3,4-dimethoxybenzophenone (1), together with a
      known C-glycosylxanthone, mangiferin (2) and two known C-glycosylflavones,
      isovitexin (3) and isoorientin (4), were isolated from the flowers of Rhynchosia
      suaveolens DC. (Fabaceae). The structure of the new compound (1) and the known
      compounds (2-4) were elucidated by extensive 1D and 2D NMR spectral studies. The
      plant extracts, as well as the isolated compounds, were evaluated for their total
      phenolic content (TPC), total flavonoid content (TFC) and DPPH radical scavenging
      activity. Among the isolated compounds, mangiferin (2) and isoorientin (4) showed
      significant radical scavenging activity comparable with that of ascorbic acid.

PMID- 25973490
TI  - Coumarins from Murraya exotica collected in Egypt.
AB  - Four new coumarins, isomurralonginol senecioate (1), isomurralonginoic acid (2),
      murrangatin 2'-formate (3), and meranzin hydrate 2'-palmitate (4), were isolated
      from the vegetative branches of Murraya exotica together with 33 known compounds.
      The structures of the new compounds were determined from chemical and
      spectroscopic data.

PMID- 25973489
TI  - Anti-vancomycin-resistant Enterococcus faecium and E. faecalis activities of (-)
      gossypol and derivatives from Thespesia garckeana.
AB  - The root extract of Thespesia garckeana yielded three known oxidatively coupled
      sesquiterpenoids, namely (-)-gossypol (1) and two of its derivatives (-)-6
      methoxygossypol (2) and (+)-6,6'-dimethoxygossypol (3), and the stem bark
      afforded (E)-docosyl-3-(3,4-dihydroxyphenyl) acrylate (4), stigmasterol (5) and
      betulinic acid (6). The structures of the isolated compounds were determined on
      the basis of full spectral data (1D and 2D NMR and HRMS) and comparison with
      literature values. Compound 1 showed potent antibacterial activity against
      vancomycin-resistant Enterococcus faecium (VRE) with IC50/MIC/MBC values of
      1.71/4.82/19.31 uM, respectively, whereas the reference standard vancomycin was
      found to be inactive. The mono- and di-methoxylated derivatives of this compound,
      (-)-6-methoxygossypol (2) and (+)-6,6'-dimethoxygossypol (3), were less active
      with respective IC50/MIC/MBC values of 2.73/4.70/9.40 uM and 6.14/18.32/18.32 uM
      against this microbe. Compound 2 was more potent than 1 against the low level VRE
      strain with I50/MIC/MBC values of 4.34/9.40/9.40 uM (vs 5.23/19.31/19.3 uM for
      1). This compound also showed interesting activities against Candida glabrata
      with an I50 value of 2.97 uM, but was less active against methicillin-resistant
      S. aureus (MRSA) exhibiting an IC50 value of 17.33 uM. Compound 1 demonstrated
      modest activity against the

PMID- 25973491
TI  - Two chlorinated benzofuran derivatives from the marine fungus Pseudallescheria
      boydii.
AB  - The marine fungus Pseudallescheria boydii was isolated from the inner tissue of
      the starfish Acanthaster planci. This fungus was cultured in a high salinity
      glucose-peptone-yeast extract (GPY) medium. Two new chlorinated benzofuran
      derivatives, 6-chloro-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5 hydroxybenzofuran
      (1) and 7-chloro-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-hydroxybenzofuran (2),
      were obtained from the extract of the culture broth. Their structures were
      determined by analysis of the NMR and MS data.

PMID- 25973492
TI  - A new citrinin dimer isolated from Aspergillus terreus strain ZDF21.
AB  - Dicitrinin E (1), a new citrinin dimer, together with the known metabolites,
      dicitrinin A (2), citrinin (3), and fumitremorgin C (4), were isolated from the
      broth culture of Aspergillus terreus strain ZDF21. The structure of dicitrinin E
      (1) was elucidated through detailed analysis of 1D and 2D NMR experiments, CD and
      mass spectra The cytotoxicity of 1 was tested against larvae of Artemia salina.

PMID- 25973493
TI  - A new naphthoquinone from Sinningia leucotricha (Gesneriaceae).
AB  - A new naphthoquinone, 7,8-dimethoxydunnione (1), was isolated from Sinningia
      leucotricha (Hoehne) Moore tubers, together with four known compounds: 7- hydroxy
      t-dunnione (2), 6-methoxy-7-hydroxy-a-dunnione (3), presilphiperfolan-9-ol (4),
      and betulinic acid (5). All compounds were identified by spectroscopic and mass
      spectrometric techniques and comparison with literature data. Compounds 2-5 are
      being reported for the first time in S. leucotricha.

PMID- 25973494
TI  - Caffeic acid: potential applications in nanotechnology as a green reducing agent
      for sustainable synthesis of gold nanoparticles.
AB  - The sustainable synthesis of gold nanoparticles from gold ions was conducted with
      caffeic acid as a green reducing agent. The formation of gold nanoparticles was
      confirmed by spectroscopic and microscopic methods. Spherical nanoparticles with
      an average diameter of 29.99 +/- 7.43 nm were observed in high- resolution
      transmission electron microscopy and atomic force microscopy images. The newly
      prepared gold nanoparticles exhibited catalytic activity toward the reduction of
      4-nitrophenol to 4-aminophenol in the presence of sodium borohydride. This system
      enables the preparation of green catalysts using plant natural products as
      reducing agents, which fulfills the growing need for sustainability initiatives.

PMID- 25973495
TI  - Anti-allergic inflammatory activities of compounds of amomi fructus.
AB  - Activity-guided isolation of compounds from the fruits of Amomum xanthioides
      resulted in the purification of fourteen phenolic compounds, 4-hydroxy
      benzaldehyde (1), 3,4-dihydroxybenzaldehyde (2), 3,5-dimethoxy-4
      methylbenzaldehyde (3), syringic aldehyde (4), benzoic acid (5), 3,4-dihydroxy
      benzoic acid (6), vanillic acid (7), 3-hydroxy-2-methoxybenzoic acid (8), o
      vanillic acid (9), phenylacetic acid (10), tyrosol (11), pyrocatechol (12),
      1,2,4,5-tetramethoxybenzene (13), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol
      (14). To evaluate the anti-allergic inflammatory activities of these compounds,
      we examined the inhibitory effects of the isolates (1-14) on histamine release
      and on the expressions of tumor necrosis factor (TNF)-ca and interleukin (IL)-6
      genes by using human mast cells. Of the tested compounds, 9, 11, and 13
      suppressed histamine release from mast cells, and all isolates attenuated the
      expressions of the pro-inflammatory cytokines, TNF-alpha and IL-6 genes in human
      mast cells.

PMID- 25973496
TI  - Chemical constituents and derivatization of melodorinol from the roots of
      Melodorum fruticosum.
AB  - Chemical investigation of the CH2Cl2 and MeOH crude extracts of the roots of
      Melodorum fruticosum Lour. led to the isolation of 15 known compounds, of which
      5, 10, and 12-15 are reported for the first time from this plant. In addition,
      melodorinol (7) was derivatized to afford six new (7a-7d and 7f-7g) analogues and
      one known compound (7e). Their structures were identified on the basic of
      spectroscopic data Most of them were evaluated for their cytotoxicity against KB,
      HeLa, MCF-7 and HepG-2 cell lines. Compounds 4 and 7b were the most potent to all
      cell lines.

PMID- 25973497
TI  - New bicyclo-spartinols from the marine-derived fungus Phaeosphaeria spartinae.
AB  - Investigation of the marine-derived fungus Phaeosphaeria spartinae, an endophyte
      of the marine alga Ceramium sp., led to the isolation of the unprecedented
      polyketides 1 and 2. The structures of these compounds were established from
      extensive spectroscopic analyses.

PMID- 25973498
TI  - Hydropiperside, a new sphingoglycolipid from Polygonum hydropiper.
AB  - One new sphingoglycolipid, hydropiperside, along with two known compounds,
      flaccidine and quercetin were isolated from the methanolic extract of Polygonum
      hydropiper. Elucidation of structures was achieved by NMR (1D and 2D) data, mass
      (EI and FAB) spectroscopy and chemical means.

PMID- 25973499
TI  - Synthetic studies of enacyloxins: a series of antibiotics isolated from Frateuria
      sp. W-315: C1'-C8' and C9'-C15' fragments.
AB  - Synthetic studies of enacyloxins (ENXs), a series of yellow-colored, polyene
      polyol antibiotics produced by Frateuria sp. W-315, are described. The C1'-C8'
      polyene fragments were prepared using successive Wittig reactions. The C9'-C15'
      and C10'-C15' fragments were constructed from (S)-isopropylideneglyceraldehyde
      using Yamaguchi's nucleophilic substitution reaction of acetylide to epoxide,
      and/or Marshall's allenylindium mediated reaction as the key steps.

PMID- 25973500
TI  - Chemical composition of the essential oil of Laserpitium latifolium from Serbia.
AB  - The essential oil of aerial parts ofLaserpitium latifolium L. from Serbia,
      obtained by hydro distillation, was analyzed by GC-MS and GC-FID applying liquid
      injection mode; thirty-four compounds were registered (99.9% of the total oil).
      The essential oil clearly belongs to the monoterpenoid chemotype, with
      monoterpenoids constituting 99.8% of the total oil. Sabinene (47.8%), alpha
      pinene (25.0%) and beta-pinene (7.1%) were the major constituents.

PMID- 25973501
TI  - Chemical composition of the essential oil of Gynoxys meridana from Merida,
      Venezuela.
AB  - The volatile components from the fresh leaves of Gynoxys meridana Cuatrec. were
      obtained by hydrodistillation and analyzed by GC/MS. A total of 25 compounds,
      representing 99.3% of the oil, were identified. The dominant compounds were gamma
      curcumene (31.9%), fukinanolide (22.3%), beta-pinene (9.5%), alpha-phellandrene
      (7.1%) and alpha-pinene (5.7%).

PMID- 25973502
TI  - Chemical composition and antibacterial activity of the essential oil of
      Ruilopezia bracteosa.
AB  - The essential oil from the leaves ofRuilopezia bracteosa was obtained by
      hydrodistillation, and analyzed by GC-MS. Eighteen components, which made up
      99.6% of the oil were identified, the most abundant being beta-myrcene (34.2%),
      alpha-pinene (24.3%), 7-epi-alpha-selinene (9.1%), beta-pinene (8.5%) and 6,9
      guaiadiene (4.4%). Antibacterial activity was tested against Gram-positive and
      Gram-negative bacteria using broth microdilution and disk agar diffusion methods.
      MIC values found presented significant differences between both methods, which
      may be due to diffusion factors.

PMID- 25973503
TI  - Comparison of the chemical composition of Valeriana parviflora essential oils
      collected in the Venezuelan Andes in two different seasons.
AB  - The essential oils obtained by hydrodistillation of the aerial parts of
      Valerianaparviflora (Trevir) BM Vadillo, an endemic species of the Venezuelan
      Andes, collected from the same location in two different seasons (dry and rainy)
      of the year, were analyzed by GC/MS. The essential oil obtained during the dry
      season showed linalool (11.9%), eugenol (8.9%), p-menth-l-en-9-al (8.7%) and
      alpha-terpineol (7.7%) as main components, while the oil obtained from the rainy
      season collection showed o-xylol (16.2%), 3-methyl isovaleric acid (10.6%) and
      geranial (9.5%) as major compounds. Some of the differences in the composition of
      these oils might be due to the climatic conditions at the time of harvesting.

PMID- 25973504
TI  - Endemic Balkan parsnip Pastinaca hirsuta: the chemical profile of essential oils,
      headspace volatiles and extracts.
AB  - The present study for the first time reports the chemical composition of the
      endemic Balkan parsnip Pastinaca hirsuta Pancic essential oil and headspace (HS)
      volatiles, obtained from fresh roots, stems, flowers and fruits, as well as fresh
      fruits n-hexane and diethyl ether extracts. According to GC-MS and GC-FID
      analyses, beta-Pinene was one of the major components of the root and stem HS
      volatiles (50.6-24.1%). (E)-beta-Ocimene was found in a significant percentage in
      the stem and flowers HS volatiles (31.6-57.3%). The most abundant constituent of
      the fruit HS, flower and fruit essential oils and both extracts was hexyl
      butanoate (70.5%, 31.1%, 80.4%, 47.4% and 52.7%, respectively). Apiole,
      accompanied by myristicin and (Z)-falcarinol, make up over 70% of the root
      essential oils. gamma-Palmitolactone was the major component of the stem
      essential oils (51.9% at the flowering stage and 45.7% at the fruiting stage).
      Beside esters as dominant compounds, furanocoumarins were also identified in
      extracts. (Dis)similarity relations of examined plant samples were also
      investigated by the agglomerative hierarchical cluster analysis. The obtained
      results show there is difference in the composition of volatile components from
      different plant organs, while the stage of growth mainly affects the quantitative
      volatiles composition.

PMID- 25973505
TI  - Chemical composition and anti-mildew activities of essential oils from different
      parts of Michelia compressa var.formosana.
AB  - In this study, anti-mildew activities of the essential oils of the leaves, wood,
      twigs, flowers, and their constituents from Michelia comnpressa var. formosana
      were evaluated in vitro against 7 mildew fungi. The main compounds responsible
      for the anti-mildew activities were isolated and identified. The essential oils
      from the fresh leaves, wood, twigs, and flowers of M. compressa var. formosana
      were isolated using hydrodistillation in a Clevenger-type apparatus, and
      characterized by GC-FID and GC-MS. The essential oil yield from the flowers was
      the highest, and the oils obtained from the 4 parts of the tree were composed
      mainly of sesquiterpenoids. The leaf oil consisted primarily of alpha-cadinol
      (18.9%) and germacrene D (18.5%); the twig oil's main constituent was alpha
      cadinol (19.1%); the wood oil's major components were alpha-cadinol (25.7%) and
      beta-eudesmol (20.2%); and the flower oil contained alpha-cadinol (11.4%).
      Comparing the anti-mildew activities of the oils suggested that wood oil was the
      most effective. Further fractionation of the wood oil produced alpha-cadinol,
      beta-eudesmol, tau-cadinol, and elemol. The 4 compounds exhibit very strong anti
      mildew activities, and these in descending order are alpha-cadinol, elemol, beta
      eudesmol, and tau-cadinol. For the anti-mildew activities of the wood oil, the
      active source compounds were determined to be alpha-cadinol, elemol, beta
      eudesmol, and tau-cadinol.

PMID- 25973506
TI  - Analgesic and antiinflammatory activities of the essential oil of the unique
      plant Zhumeria majdae.
AB  - The analgesic and anti-inflammatory properties of Zhumeria majdae essential oil
      were investigated in mice and rats. The analgesic activity of the oil was
      assessed by acetic acid-induced writhing and Eddy's hot plate methods while the
      acute anti-inflammatory effect was investigated by inflammatory paw edema in rat.
      Z majdae oil significantly decreased the number of acetic acid-induced writhes in
      mice compared with animals that received vehicle only. Also it exhibited a
      central analgesic effect as evidenced by a significant increase in reaction time
      in the hot plate method. The oil also significantly reduced carrageenan induced
      paw edema in rats. The inhibitory activity of Z. majdae essential oil was found
      to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The
      studied oil was analyzed by GC and GC-MS and seventeen constituents were
      identified, representing 99.2% of the oil. The major components of the oil were
      characterized as linalool (63.4%) and camphor (27.5%), which might be responsible
      for these observed activities. The results suggest that Z. majdae essential oil
      possesses biologically active constituent(s) that have significant activity
      against acute inflammation and have central and peripheral antinociceptive
      effects which support the ethnomedicinal claims of the plant application in the
      management of pain and inflammation.

PMID- 25973507
TI  - Antimicrobial activity and chemical composition of the essential oils of
      Portuguese Foeniculum vulgare fruits.
AB  - The aim of this study was to investigate the chemical composition and
      antimicrobial activity of essential oils obtained by hydrodistillation from
      fruits of six fennel accessions collected from wild populations occurring in the
      centre and south of Portugal. Composition of essential oils was established by
      Gas Chromatography-Flame Ionization Detector (GC-FID) and Gas Chromatography-Mass
      Spectrometry (GC-MS) analysis. The obtained yields of the essential oils were
      found to vary greatly in the range of 1.1 to 2.9% (v/w) and the chemical
      composition varied with the region of collection. A total of 16 compounds were
      identified. The main compounds were fenchone (16.9 - 34.7%), estragole (2.5 -
      66.0%) and trans-anethole (7.9 - 77.7%). The percentages of these three main
      compounds were used to determine the relationship between the different oil
      samples and to group them into four different chemotypes: anethole/fenchone;
      anethole; estragole and anethole/estragole. Antifungal activity of essential oils
      was evaluated against six food spoilage fungi: Aspergillus niger, A. japonicus,
      A. oryzae, Fusarium oxysporum, Rhizophus oryzae and R. stolonifer. Antibacterial
      activity was assessed against three Gram-positive strains: Enterococcus faecalis
      ATCC 29212, Staphylococcus epidermidis ATCC 12228 and S. aureus ATCC 28213; and
      against six Gram-negative strains: Escherichia coli ATCC 25922; Morganella
      morganii LFG 08; Proteus mirabilis LFG 04; Salmonella enteritidis LFG 05; S.
      entiritidis serovar typhimurium LFG 06 and Pseudomonas aeruginosa ATCC 27853 by
      the disc diffusion agar method; the minimal inhibitory concentration (MIC) was
      determined using the broth macro-dilution method. The MIC values varied from 62.5
      (E. coli ATCC 25922) to 2000 umL (P. aeruginosa ATCC 27853).

PMID- 25973508
TI  - Larvicidal activity against Aedes aegypti of Foeniculum vulgare essential oils
      from Portugal and Cape Verde.
AB  - Dengue is a potentially fatal mosquito-borne infection with 50 million cases per
      year and 2.5 billion people vulnerable to the disease. This major public health
      problem has recurrent epidemics in Latin America and occurred recently in Cape
      Verde and Madeira Island. The lack of anti-viral treatment or vaccine makes the
      control of mosquito vectors a high option to prevent virus transmission.
      Essential oil (EO) constituents can affect insect's behaviour, being potentially
      effective in pest control. The present study evaluated the potential use of
      Foenicultm vulgare (fennel) EO in the control of the dengue vector Aedes aegypti.
      EOs isolated from fennel aerial parts collected in Cape Verde and from a
      commercial fennel EO of Portugal were analysed by NMR, GC and GC-MS. trans
      Anethole (32 and 30%, respectively), limonene (28 and 18%, respectively) and
      fenchone (10% in both cases) were the main compounds identified in the EOs
      isolated from fennel from Cape Verde and Portugal, respectively. The larvicidal
      activity of the EOs and its major constituents were evaluated, using WHO
      procedures, against third instar larvae ofAe. aegypti for 24 h. Pure compounds,
      such as limonene isomers, were also assayed. The lethal concentrations LC50, C90
      and LC99 were determined by probit analysis using mortality rates of bioassays. A
      99% mortality of Ae. aegypti larvae was estimated at 37.1 and 52.4 uL L-1 of
      fennel EOs from Cape Verde and Portugal, respectively. Bioassays showed that
      fennel EOs from both countries displayed strong larvicidal effect against Ae.
      aegypti, the Cape Verde EO being as active as one of its major constituents, (-)
      limonene.

PMID- 25973509
TI  - Chemical constituents of the genus Polygonatum and their role in medicinal
      treatment.
AB  - Polygonatum is a famous traditional Chinese medicine that is widely used in
      China, Korea and Japan. In the last decade, constituents of the genus have been
      reported including steroidal saponins, flavones, alkaloids, lignins, amino acids
      and carbohydrates, some of which show biological properties such as antiviral and
      antitumor activity, variable effects on the immune system and anticoagulant
      activity. In addition, some findings provide novel evidence that Polygonatum
      species may contain potential anti-tumor and anti-viral proteins for possible
      medical application and large-scale pharmaceutical production. In this review, we
      focus on the updated research of the chemical constituents of Polygonatum
      including polysaccharides, steroidal saponins, flavonoids and lectins, and their
      potential therapeutic roles.

PMID- 25973517
TI  - Anti-inflammatory and Anti-nociceptive Activity of Ruthenium Complexes with
      Isonicotinic and Nicotinic Acids (Niacin) as Ligands.
AB  - This work evaluated the analgesic and anti-inflammatory activity of ruthenium(II)
      complexes trans-[Ru(NO(+))(NH3)4(L)](BF4)3 and [Ru(NH3)5(L)](BF4)3 containing the
      nonsteroidal anti-inflammatory drugs nicotinic acid (Hnic) and its isomer
      isonicotinic acid (ina) as ligands (L). The anti-nociceptive potential of these
      complexes and the free ligands (noncoordinated to ruthenium) was tested in
      different models with doses ranging from 1 to 100 MUmol/kg. The ligands
      themselves were inactive; however, the ruthenium complexes containing Hnic and
      ina inhibited mechanical hyperalgesia induced by prostaglandin E2, carrageenan
      induced hyperalgesia, and antigen-induced arthritis. Moreover, the ruthenium
      complexes inhibited overt nociception induced by formalin, acetic acid,
      capsaicin, and cinnamaldehyde. The mechanism involved in the anti-nociceptive
      effects of the ruthenium complexes suggested that ATP-sensitive K(+) channel
      pathways were not involved because glibenclamide did not affect their anti
      nociceptive activities. However, the anti-nociceptive effect appears to be a
      consequence of the reduction in neutrophil migration and inhibition of the
      protein kinase C pathway. 

PMID- 25973518
TI  - Neurodegeneration with Brain Iron Accumulation: Genetic Diversity and
      Pathophysiological Mechanisms.
AB  - Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous
      group of progressive disorders with the common feature of excessive iron
      deposition in the brain. Over the last decade, advances in sequencing
      technologies have greatly facilitated rapid gene discovery, and several single
      gene disorders are now included in this group. Identification of the genetic
      bases of the NBIA disorders has advanced our understanding of the disease
      processes caused by reduced coenzyme A synthesis, impaired lipid metabolism,
      mitochondrial dysfunction, and defective autophagy. The contribution of iron to
      disease pathophysiology remains uncertain, as does the identity of a putative
      final common pathway by which the iron accumulates. Ongoing elucidation of the
      pathogenesis of each NBIA disorder will have significant implications for the
      identification and design of novel therapies to treat patients with these
      disorders. 

PMID- 25973520
TI  - Commentary: When does understanding phenotypic evolution require identification
      of the underlying genes?
AB  - Adaptive evolution is fundamentally a genetic process. Over the past three
      decades, characterizing the genes underlying adaptive phenotypic change has
      revealed many important aspects of evolutionary change. At the same time, natural
      selection is often fundamentally an ecological process that can often be studied
      without identifying the genes underlying the variation on which it acts. This
      duality has given rise to disagreement about whether, and under what
      circumstances, it is necessary to identify specific genes associated with
      phenotypic change. This issue is of practical concern, especially for researchers
      who study nonmodel organisms, because of the often enormous cost and labor
      required to "go for the genes." We here consider a number of situations and
      questions commonly addressed by researchers. Our conclusion is that although gene
      identification can be crucial for answering some questions, there are others for
      which definitive answers can be obtained without finding underlying genes. It
      should thus not be assumed that considerations of "empirical completeness"
      dictate that gene identification is always desirable. 

PMID- 25973519
TI  - Ethanol Modulation is Quantitatively Determined by the Transmembrane Domain of
      Human alpha1 Glycine Receptors.
AB  - BACKGROUND: Mutagenesis and labeling studies have identified amino acids from the
      human alpha1 glycine receptor (GlyR) extracellular, transmembrane (TM), and
      intracellular domains in mediating ethanol (EtOH) potentiation. However, limited
      high-resolution structural data for physiologically relevant receptors in this
      Cys-loop receptor superfamily have made pinpointing the critical amino acids
      difficult. Homologous ion channels from lower organisms provide conserved models
      for structural and functional properties of Cys-loop receptors. We previously
      demonstrated that a single amino acid variant of the Gloeobacter violaceus ligand
      gated ion channel (GLIC) produced EtOH and anesthetic sensitivity similar to that
      of GlyRs and provided crystallographic evidence for EtOH binding to GLIC.
      METHODS: We directly compared EtOH modulation of the alpha1 GlyR and GLIC to a
      chimera containing the TM domain from human alpha1 GlyRs and the ligand-binding
      domain of GLIC using 2-electrode voltage-clamp electrophysiology of receptors
      expressed in Xenopus laevis oocytes. RESULTS: EtOH potentiated alpha1 GlyRs in a
      concentration-dependent manner in the presence of zinc-chelating agents, but did
      not potentiate GLIC at pharmacologically relevant concentrations. The GLIC/GlyR
      chimera recapitulated the EtOH potentiation of GlyRs, without apparent
      sensitivity to zinc chelation. For chimera expression in oocytes, it was
      essential to suppress leakage current by adding 50 MUM picrotoxin to the media, a
      technique that may have applications in expression of other ion channels.
      CONCLUSIONS: Our results are consistent with a TM mechanism of EtOH modulation in
      Cys-loop receptors. This work highlights the relevance of bacterial homologs as
      valuable model systems for studying ion channel function of human receptors and
      demonstrates the modularity of these channels across species.

PMID- 25973521
TI  - Visible-Light-Induced Self-Cleaning Property of Bi2Ti2O7-TiO2 Composite Nanowire
      Arrays.
AB  - Bi2Ti2O7-TiO2 composite nanowire arrays were prepared via a two-step sequential
      solvothermal and subsequent calcination process. The morphology and structure of
      the Bi2Ti2O7-TiO2 composite nanowire array composite were characterized by X-ray
      diffraction, field emission scanning electron microscopy, and transmission
      electron microscopy. The UV-visible diffuse reflectance spectroscopy analysis
      indicated that the absorption spectrum of the Bi2Ti2O7-TiO2 composite nanowire
      array composite was extended to the visible-light region due to the existence of
      Bi2Ti2O7. The Bi2Ti2O7-TiO2 composite nanowire arrays exhibit superhydrophilicity
      with water contact angles of 0 degrees  after irradiation with visible light, and
      the superhydrophilic nature is retained for at least 15 days. This effect enables
      us to consider self-cleaning applications that do not require permanent UV
      exposure. Compared to pure Bi2Ti2O7 and TiO2, the vertically aligned Bi2Ti2O7
      TiO2 composite nanowire arrays showed more significant visible-light self
      cleaning performance due to the synergistic effect of superhydrophilicity and
      significant photocatalytic activity caused by effective electron-hole separation
      at the interfaces of the two semiconductors, which was confirmed by the
      electrochemical analysis and surface photovoltage technique. 

PMID- 25973522
TI  - Report of the Havemeyer Foundation Workshop on Equine Implantation: Is early
      pregnancy loss the only important potential consequence of disturbed
      preimplantation development?

PMID- 25973523
TI  - The role of professional and team commitment in nurse-physician collaboration: A
      dual identity model perspective.
AB  - Nurse-physician collaboration involves healthcare operators from different
      professions working together. The dual identity model predicts that nurse
      physician interprofessional collaboration could improve if these operators feel
      they belong to both their professional category and care unit. This study tested
      this prediction by analyzing the effect of professional and team commitments on
      interprofessional collaboration between nurses and physicians in a hospital based
      in Northern Italy. A cross-section questionnaire survey was administered to 270
      nurses and 95 physicians. Results indicate that interprofessional collaboration
      is positively affected by team commitment, while professional commitment had no
      effect. In accordance with the dual identity model, results indicate that
      interprofessional collaboration is higher when: (i) both professional and team
      commitment is high, and (ii) when team commitment is high and professional
      commitment is low. These results support dual identity model predictions and
      suggest that interprofessional collaboration can be increased by bolstering both
      team and professional commitment of nurses and physicians. 

PMID- 25973524
TI  - A Novel Hybrid Approach for Balloon Dilation of Pulmonary Vein Stenosis Following
      Total Anomalous Pulmonary Venous Connection Repair with Atrial Septal Patching.
AB  - Pulmonary venous obstruction after the repair of total anomalous pulmonary venous
      connection is a serious complication. Transcatheter interventional treatment is a
      palliative choice to defer the timing of surgery; however, penetrating through
      the patched atrial septum may be difficult. We report a technique for pulmonary
      venous obstruction after mixed-type total anomalous pulmonary venous connection
      repair using balloon dilatation of the pulmonary veins through a novel hybrid
      approach.

PMID- 25973525
TI  - Molecular Polymorphism in the MTA and MTB Mating Type Genes of Tetrahymena
      thermophila and Related Asexual Species.
AB  - Each of the seven mating types of Tetrahymena thermophila is determined by a pair
      of large genes, MTA and MTB, whose expression peaks at early conjugation. Each
      protein consists of a mating-type specific domain and a common transmembrane
      domain. To assess variation in natural populations, regions of both domains from
      wild isolates expressing mating types V and VII were analyzed. Corresponding
      regions of amicronucleates incapable of mating also were examined. MTA and MTB
      showed high haplotype diversity, with greater sequence variation in MTB. Mating
      type VII was less variable than mating type V, suggesting more recent origin. No
      polymorphism distinguished between mat1- and mat2-like alleles encoding different
      arrays of mating types, nor did polymorphisms give evidence of population
      structure. MTA and MTB variants have different phylogenies, suggesting
      independent rather than concerted evolution, and are under weak purifying
      selection. Codon usage is less biased than for housekeeping genes, and reassigned
      glutamine encoding stop codons are preferentially used. Amicronucleate T.
      thermophila and closely related nsp15 and nsp25 have higher levels of nucleotide
      and amino acid substitution, consistent with cox1 distances. The results suggest
      that complete sequencing of mating type genes of wild isolates coupled with
      functional analysis will be informative. 

PMID- 25973527
TI  - Infant sleep and night feeding patterns during later infancy: association with
      breastfeeding frequency, daytime complementary food intake, and infant weight.
AB  - Infant sleep is a common concern for new parents. Although many expect a newborn
      infant to wake frequently, encouraging a baby to sleep through the night by a few
      months of age is seen as both a developmental aim and a parenting success. Many
      new mothers believe that their infants' diet is related to their sleep; formula
      milk or increased levels of solid food are often given in an attempt to promote
      sleep. However, the impact of these in later infancy is not understood. In the
      current study 715 mothers with an infant 6-12 months of age reported their
      infants' typical night wakings and night feeds alongside any breastfeeding and
      frequency of solid meals. Of infants in this age range, 78.6% still regularly
      woke at least once a night, with 61.4% receiving one or more milk feeds. Both
      night wakings and night feeds decreased with age. No difference in night wakings
      or night feeds was found between mothers who were currently breastfeeding or
      formula feeding. However, infants who received more milk or solid feeds during
      the day were less likely to feed at night but not less likely to wake. The
      findings have important implications for health professionals who support new
      mothers with infant sleep and diet in the first year. Increasing infant calories
      during the day may therefore reduce the likelihood of night feeding but will not
      reduce the need for parents to attend to the infant in the night. Breastfeeding
      has no impact on infant sleep in the second 6 months postpartum. 

PMID- 25973526
TI  - Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and
      Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study
      and Open-Label Extension.
AB  - BACKGROUND: Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is
      efficacious and well tolerated in inducing bowel movements in patients with
      advanced illness and opioid-induced constipation (OIC); however, fixed-dose
      administration of MNTX may improve ease of administration. OBJECTIVE: The study
      objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4
      trials. METHODS: In a double-blind, randomized, placebo-controlled trial (RCT),
      patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body
      weight [38 kg to <62 kg or >=62 kg, respectively]) or placebo every other day
      (QOD) for two weeks. Patients completing the RCT could enroll in an open-label
      extension (OLE) study with MNTX administered as needed (PRN). The primary
      endpoint was percentage of patients with a rescue-free bowel movement (RFBM)
      within four hours after >=2 of the first 4 doses in the first week. RESULTS: In
      the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149
      patients continued to the OLE study. The percentage of patients achieving primary
      endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001).
      Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and
      placebo groups, respectively (p<0.0001). Efficacy results during the OLE study
      were consistent with the RCT. MNTX demonstrated a favorable safety profile in the
      RCT and OLE study. CONCLUSION: Fixed-dose MNTX administered QOD in the RCT and
      PRN in the OLE study demonstrated robust efficacy and was well tolerated in
      treating OIC in patients with advanced illness.

PMID- 25973528
TI  - Coproduct Promoted Povarov Reaction: Synthesis of Substituted Quinolines from
      Methyl Ketones, Arylamines, and alpha-Ketoesters.
AB  - A highly efficient I2-catalyzed Povarov-type reaction of methyl ketones,
      arylamines, and alpha-ketoesters is developed. This reaction utilizes a catalytic
      amount of HI coproduct as a promoter for the synthesis of substituted quinolones.
      This simple procedure represents an interesting new form of reactivity for the
      Povarov reaction with good functional group compatibility. 

PMID- 25973529
TI  - Reply to Letter to the Editor: Wink Glass, Incomplete Blink and Computer Vision
      Syndrome.

PMID- 25973530
TI  - Prevalence of overweight, obesity and metabolic syndrome components in multiple
      sclerosis patients with significant disability.
AB  - BACKGROUND AND PURPOSE: Information about metabolic comorbidities in patients
      with multiple sclerosis (MS) is scarce. Our aim was to examine the prevalence of
      the metabolic syndrome (MetS) and its components in patients with long duration
      of MS and significant disability. METHODS: Demographic and clinical data, weight,
      height, waist circumference, blood pressure, and levels of fasting glucose,
      triglycerides and high density lipoprotein cholesterol (HDL-C) were obtained from
      130 MS patients with Extended Disability Status Scale (EDSS) score >=3.0.
      RESULTS: Seventy-two percent were female, mean +/- SD age 55.8 +/- 6.0, range 45
      65 years, disease duration 18.2 +/- 10.1 years, EDSS 5.5 +/- 1.0. Obesity [body
      mass index (BMI) >= 30 kg/m(2) ] was present in 18.5% and overweight (BMI 25.0
      29.9 kg/m(2) ) in 34.6%. The prevalence of the MetS was 30% with no gender
      difference. Fifty-six percent had central obesity by waist circumference, 28%
      treated hypertension, 45.8% elevated blood pressure, 11% type 2 diabetes
      mellitus, 31.4% treated dyslipidemia, 28.8% elevated triglyceride levels and
      31.4% had low HDL-C. MS patients with MetS were significantly older (59.0 +/- 5.5
      vs. 53.8 +/- 5.5, P < 0.0001) and heavier (BMI 29.0 +/- 6.9 vs. 25.1 +/- 4.7, P =
      0.0009). There were no differences between the groups in neurological disability
      by the EDSS (5.7 +/- 1.0 vs. 5.4 +/- 1.0), disease duration (18.4 +/- 9.9 vs.
      18.2 +/- 10.2 years) and number of steroid courses received (6.6 +/- 9.5 vs. 6.3
      +/- 8.4). CONCLUSIONS: Compared to the general population, adult disabled MS
      patients had lower rates of obesity and overweight, as assessed by BMI. Despite
      these reduced rates, the prevalence of the MetS was similar to the general
      population. Specifically higher rates of increased waist circumference were
      found, suggesting that the lower BMI may be misleading in terms of health risk.

PMID- 25973531
TI  - Simultaneous Quantitation of Na(+) and K(+) in Single Normal and Cancer Cells
      Using a New Near-Infrared Fluorescent Probe.
AB  - Considering the important functions of cellular Na(+) and K(+) together with
      their cooperative efforts on various biological processes, it is significant to
      simultaneously detect Na(+) and K(+) at a single-cell level. Here, we present a
      novel method to discriminate and quantify simultaneously Na(+) and K(+) in single
      cells using a new near-infrared fluorescent probe associated with microchip
      electrophoresis. The fluorescent probe selectively responds to both Na(+) and
      K(+). The microchip electrophoresis allows accurate single-cell manipulation and
      effective distinction of Na(+) and K(+). Based on the method, the concentration
      of Na(+) and K(+) in single normal and cancer cells was compared, and the
      variation of Na(+) and K(+) in single cancer cells during the early stage of
      apoptotic volume decrease was monitored, which would help us to better understand
      the critical roles of Na(+) and K(+) in malignant cells and apoptosis. This
      method has paved a new way for the research of the synergistic function of Na(+)
      and K(+) in the regulation of various biological processes at a single-cell
      level. 

PMID- 25973532
TI  - Home Clinical Video Telehealth Promotes Education and Communication with
      Caregivers of Veterans with TBI.
AB  - Ongoing communication and care coordination are essential among patients, their
      family, and interdisciplinary rehabilitation team members to address the complex
      and changing rehabilitation needs of traumatic brain injuries. Family members of
      patients with traumatic brain injury commonly assume a caregiver role following
      discharge from inpatient rehabilitation. The Department of Veterans Affairs has
      adopted clinical video telehealth to promote access to care, and use of clinical
      video telehealth for rehabilitation is expanding. Recent implementation of home
      clinical video telehealth can assist with the ongoing management and treatment of
      patients in their home setting. This report demonstrates enhanced education and
      care coordination by using clinical video telehealth with a Veterans Affairs
      eligible beneficiary receiving treatment for traumatic brain injury. 

PMID- 25973533
TI  - NGS-based approach to determine the presence of HPV and their sites of
      integration in human cancer genome.
AB  - BACKGROUND: Human papilloma virus (HPV) accounts for the most common cause of all
      virus-associated human cancers. Here, we describe the first graphic user
      interface (GUI)-based automated tool 'HPVDetector', for non-computational
      biologists, exclusively for detection and annotation of the HPV genome based on
      next-generation sequencing data sets. METHODS: We developed a custom-made
      reference genome that comprises of human chromosomes along with annotated genome
      of 143 HPV types as pseudochromosomes. The tool runs on a dual mode as defined by
      the user: a 'quick mode' to identify presence of HPV types and an 'integration
      mode' to determine genomic location for the site of integration. The input data
      can be a paired-end whole-exome, whole-genome or whole-transcriptome data set.
      The HPVDetector is available in public domain for download:
      http://www.actrec.gov.in/pi-webpages/AmitDutt/HPVdetector/HPVDetector.html.
      RESULTS: On the basis of our evaluation of 116 whole-exome, 23 whole
      transcriptome and 2 whole-genome data, we were able to identify presence of HPV
      in 20 exomes and 4 transcriptomes of cervical and head and neck cancer tumour
      samples. Using the inbuilt annotation module of HPVDetector, we found predominant
      integration of viral gene E7, a known oncogene, at known 17q21, 3q27, 7q35, Xq28
      and novel sites of integration in the human genome. Furthermore, co-infection
      with high-risk HPVs such as 16 and 31 were found to be mutually exclusive
      compared with low-risk HPV71. CONCLUSIONS: HPVDetector is a simple yet precise
      and robust tool for detecting HPV from tumour samples using variety of next
      generation sequencing platforms including whole genome, whole exome and
      transcriptome. Two different modes (quick detection and integration mode) along
      with a GUI widen the usability of HPVDetector for biologists and clinicians with
      minimal computational knowledge.

PMID- 25973534
TI  - Combination of microsatellite instability and BRAF mutation status for subtyping
      colorectal cancer.
AB  - BACKGROUND: The objective of the study was to examine the role of microsatellite
      instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by
      categorising patients into more detailed subtypes based on tumour
      characteristics. METHODS: Tumour samples from 762 population-based patients with
      sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry.
      Patient survival was followed-up for a median of 5.2 years. RESULTS: Compared
      with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free
      survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR
      0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2%
      vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type,
      BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs
      51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for
      DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk
      for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a
      prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II
      patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS
      (HR: 5.32, CI: 1.74-16.31, P=0.003). CONCLUSIONS: Microsatellite instable tumours
      were associated with better prognosis compared with MSS. BRAF(V600E) was
      associated with poor prognosis unless it occurred together with MSI. The
      MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the
      MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor
      prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease
      specific mortality even in stage I-II CRC.

PMID- 25973535
TI  - Computational study with DFT and kinetic models on the mechanism of
      photoinitiated aromatic perfluoroalkylations.
AB  - A combination of DFT calculations and kinetic models is applied to fully
      elucidate the seemingly complex reactivity of alpha-cyano arylacetates toward
      metal-free photoinitiated aromatic perfluoroalkylation. The resulting mechanistic
      framework rationalizes the observed quantum yield as well as the differences in
      reactivity and/or selectivity of seemingly similar substrates. The use of a
      kinetic model for the chemical interpretation of the DFT-computed reaction
      constants is shown to be critical. 

PMID- 25973536
TI  - Silver (I) as DNA glue: Ag(+)-mediated guanine pairing revealed by removing
      Watson-Crick constraints.
AB  - Metal ion interactions with DNA have far-reaching implications in biochemistry
      and DNA nanotechnology. Ag(+) is uniquely interesting because it binds
      exclusively to the bases rather than the backbone of DNA, without the toxicity of
      Hg(2+). In contrast to prior studies of Ag(+) incorporation into double-stranded
      DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base
      DNA oligomers of the canonical bases. High resolution electro-spray ionization
      mass spectrometry reveals an unanticipated Ag(+)-mediated pairing of guanine homo
      base strands, with higher stability than canonical guanine-cytosine pairing. By
      exploring unrestricted binding geometries, quantum chemical calculations find
      that Ag(+) bridges between non-canonical sites on guanine bases. Circular
      dichroism spectroscopy shows that the Ag(+)-mediated structuring of guanine
      homobase strands persists to at least 90  degrees C under conditions for which
      canonical guanine-cytosine duplexes melt below 20  degrees C. These findings are
      promising for DNA nanotechnology and metal-ion based biomedical science. 

PMID- 25973538
TI  - Efficiency corrections in determining the (137)Cs inventory of environmental soil
      samples by using relative measurement method and GEANT4 simulations.
AB  - The determination of (137)Cs inventory is widely used to estimate the soil
      erosion or deposition rate. The generally used method to determine the activity
      of volumetric samples is the relative measurement method, which employs a
      calibration standard sample with accurately known activity. This method has great
      advantages in accuracy and operation only when there is a small difference in
      elemental composition, sample density and geometry between measuring samples and
      the calibration standard. Otherwise it needs additional efficiency corrections in
      the calculating process. The Monte Carlo simulations can handle these correction
      problems easily with lower financial cost and higher accuracy. This work presents
      a detailed description to the simulation and calibration procedure for a
      conventionally used commercial P-type coaxial HPGe detector with cylindrical
      sample geometry. The effects of sample elemental composition, density and
      geometry were discussed in detail and calculated in terms of efficiency
      correction factors. The effect of sample placement was also analyzed, the results
      indicate that the radioactive nuclides and sample density are not absolutely
      uniform distributed along the axial direction. At last, a unified binary
      quadratic functional relationship of efficiency correction factors as a function
      of sample density and height was obtained by the least square fitting method.
      This function covers the sample density and height range of 0.8-1.8 g/cm(3) and
      3.0-7.25 cm, respectively. The efficiency correction factors calculated by the
      fitted function are in good agreement with those obtained by the GEANT4
      simulations with the determination coefficient value greater than 0.9999. The
      results obtained in this paper make the above-mentioned relative measurements
      more accurate and efficient in the routine radioactive analysis of environmental
      cylindrical soil samples. 

PMID- 25973537
TI  - Hepatic differentiation of human amniotic epithelial cells and in vivo
      therapeutic effect on animal model of cirrhosis.
AB  - BACKGROUND AND AIM: Human amniotic epithelial cells (hAECs) have been touted as
      an ideal stem cell candidate, being ethically neutral, immunologically naive,
      plentiful in origin, and retaining plasticity in its fetal stage. We hypothesized
      that by applying natural physiological signals of the developing liver, hAECs can
      be coaxed into becoming functional immunopermissive hepatocyte-like cells. These
      cells would have tremendous potential for allogenic cellular transplantation in
      the treatment of chronic liver insufficiency. METHODS: hAECs were obtained from
      term placentas and subjected to hepatic trans-differentiation. Hepatic
      differentiated cells were analyzed with immunophenotyping, electron microscopy,
      reverse transcription-polymerase chain reaction as well as characterized for
      hepatic metabolic function. In vivo efficacy was tested using intrasplenic
      transplantation into non-obese diabetic (NOD) Scid Gamma mice with thioacetamide
      induced chronic liver failure and analyzed for engraftment and improvement in
      liver indices. RESULTS: With hepatic differentiation, hAECs assumed a hepatocytic
      polygonal morphology with upregulation of transcription factors responsible for
      liver specification. These hepatic differentiated-hAECs (HD-AECs) demonstrated
      bile canaliculi formation, secreted albumin, eliminated indo-cyanine green,
      uptook low-density lipoprotein, and inducible CYP3A4 and CYP2C9 enzymatic
      activities. Transplantation of HD-AECs and de novo hAECs in mice model of
      cirrhosis showed successful in vivo engraftment and differentiation into
      functional hepatocytes positive for human-specific albumin. HD-AEC cells that had
      undergone hepatic differentiation showed the greatest improvement in albumin
      function while preserving human leukocyte antigen-G expression
      postdifferentiation. CONCLUSION: hAECs were able to differentiate into functional
      hepatocyte-like cells both in vivo and in vitro. They showed therapeutic efficacy
      after transplantation in mice model of cirrhosis, offering an exciting source of
      cells for generation of functionally useful hepatocytes.

PMID- 25973539
TI  - Nuclear accident-derived (3)H in river water of Fukushima Prefecture during 2011
      2014.
AB  - During 2011-2014, we measured (3)H concentrations in river water samples
      collected during base flow conditions and during several flood events from two
      small rivers in a mountainous area in Fukushima Prefecture, which received
      deposition of (137)Cs from the Fukushima Dai-ichi Nuclear Power Plant accident.
      (3)H concentrations above background levels were found in water samples collected
      during both base flow conditions and flood events in 2011. The (3)H
      concentrations during flood events were generally higher than those during base
      flow conditions. The (3)H concentrations in both rivers during base flow
      conditions and flood events decreased with time after the accident and reached
      almost background levels in 2013. We also measured (3)H concentrations in
      freshwater samples from 16 other rivers and one dam in eastern Fukushima
      Prefecture from 2012 to 2014 during base flow conditions. The measured (3)H
      concentrations were higher than the background level in 2012 and decreased with
      time. The (137)Cs inventory in the catchment area at each sampling point was
      estimated from air-borne monitoring results in the literature and compared with
      the (3)H concentrations. We found surprisingly good correlations between (137)Cs
      inventories in the catchment areas and (3)H concentrations in the water samples.
      Further studies will be necessary to clarify the reason for the good correlation.

PMID- 25973540
TI  - Annual variation in the atmospheric radon concentration in Japan.
AB  - Anomalous atmospheric variations in radon related to earthquakes have been
      observed in hourly exhaust-monitoring data from radioisotope institutes in Japan.
      The extraction of seismic anomalous radon variations would be greatly aided by
      understanding the normal pattern of variation in radon concentrations. Using
      atmospheric daily minimum radon concentration data from five sampling sites, we
      show that a sinusoidal regression curve can be fitted to the data. In addition,
      we identify areas where the atmospheric radon variation is significantly affected
      by the variation in atmospheric turbulence and the onshore-offshore pattern of
      Asian monsoons. Furthermore, by comparing the sinusoidal regression curve for the
      normal annual (seasonal) variations at the five sites to the sinusoidal
      regression curve for a previously published dataset of radon values at the five
      Japanese prefectures, we can estimate the normal annual variation pattern. By
      fitting sinusoidal regression curves to the previously published dataset
      containing sites in all Japanese prefectures, we find that 72% of the Japanese
      prefectures satisfy the requirements of the sinusoidal regression curve pattern.
      Using the normal annual variation pattern of atmospheric daily minimum radon
      concentration data, these prefectures are suitable areas for obtaining anomalous
      radon variations related to earthquakes. 

PMID- 25973541
TI  - Is the future of personalized therapy in triple-negative breast cancer based on
      molecular subtype?
AB  - Significant research has been conducted to better understand the extensive,
      heterogeneous molecular features of triple-negative breast cancer (TNBC). We
      reviewed published TNBC molecular classifications to identify major groupings
      that have potential for clinical trial development. With the ultimate aim to
      streamline translational medicine, we linked these categories of TNBC according
      to their gene-expression signatures, biological function, and clinical outcome.
      To this end, we define five potential clinically actionable groupings of TNBC: 1)
      basal-like TNBC with DNA-repair deficiency or growth factor pathways; 2)
      mesenchymal-like TNBC with epithelial-to-mesenchymal transition and cancer stem
      cell features; 3) immune-associated TNBC; 4) luminal/apocrine TNBC with androgen
      receptor overexpression; and 5) HER2-enriched TNBC. For each defined subtype, we
      highlight the major biological pathways and discuss potential targeted therapies
      in TNBC that might abrogate disease progression. However, many of these potential
      targets need clinical validation by clinical trials. We have yet to know how we
      can enrich the targets by molecular classifications. 

PMID- 25973542
TI  - The EMT-activator ZEB1 induces bone metastasis associated genes including BMP
      inhibitors.
AB  - Tumor cell invasion, dissemination and metastasis is triggered by an aberrant
      activation of epithelial-to-mesenchymal transition (EMT), often mediated by the
      transcription factor ZEB1. Disseminating tumor cells must acquire specific
      features that allow them to colonize at different organ sites. Here we identify a
      set of genes that is highly expressed in breast cancer bone metastasis and
      activated by ZEB1. This gene set includes various secreted factors, e.g. the BMP
      inhibitor FST, that are described to reorganize the bone microenvironment. By
      inactivating BMP-signaling, BMP-inhibitors are well-known to induce osteolysis in
      development and disease. We here demonstrate that the expression of ZEB1 and BMP
      inhibitors is correlated with bone metastasis, but not with brain or lung
      metastasis of breast cancer patients. In addition, we show that this correlated
      expression pattern is causally linked, as ZEB1 induces the expression of the BMP
      inhibitors NOG, FST and CHRDL1 both by directly increasing their gene
      transcription, as well as by indirectly suppressing their reduction via miR-200
      family members. Consequently, ZEB1 stimulates BMP-inhibitor mediated osteoclast
      differentiation. These findings suggest that ZEB1 is not only driving EMT, but
      also contributes to the formation of osteolytic bone metastases in breast cancer.

PMID- 25973544
TI  - LC-ESI-MS/MS analysis of quercetin in rat plasma after oral administration of
      biodegradable nanoparticles.
AB  - A simple, rapid and sensitive LC-MS/MS method was developed and validated for the
      determination of free quercetin in rat plasma, using fisetin as internal
      standard. The detection was performed by negative ion electrospray ionization
      under selected reaction monitoring. Chromatographic separation (isocratic
      elution) was carried out using acetonitrile-10 m m ammonium formate (80:20, v/v)
      with 0.1% v/v formic acid. The lower limit of quantification (4.928 ng/mL)
      provided high sensitivity for the detection of quercetin in rat plasma. The
      linearity range was from 5 to 2000 ng/mL. Intra- and inter-day variability (RSD)
      of quercetin extraction from rat plasma was <4.19 and 1.37% with accuracies of
      98.77 and 99.67%. The method developed was successfully applied for estimating
      free quercetin in rat plasma, after oral administration of quercetin-loaded
      biodegradable nanoparticles (QLN) and quercetin suspension. QLN (C(max), 1277.34
      +/- 216.67 ng/mL; AUC, 17,458.25 +/- 3152.95 ng hr/mL) showed a 5.38-fold
      increase in relative bioavailability as compared with quercetin suspension
      (C(max), 369.2 +/- 108.07 ng/mL; AUC, 3276.92 +/- 396.67 ng hr/mL).

PMID- 25973543
TI  - Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer
      cell migration and invasion through FGFR-SRC signaling and integrin alphavbeta5
      mediated adhesion.
AB  - Carcinoma-associated fibroblasts were reported to promote colorectal cancer (CRC)
      invasion by secreting motility factors and extracellular matrix processing
      enzymes. Less is known whether fibroblasts may induce CRC cancer cell motility by
      contact-dependent mechanisms. To address this question we characterized the
      interaction between fibroblasts and SW620 and HT29 colorectal cancer cells in 2D
      and 3D co-culture models in vitro. Here we show that fibroblasts induce contact
      dependent cancer cell elongation, motility and invasiveness independently of
      deposited matrix or secreted factors. These effects depend on fibroblast cell
      surface-associated fibroblast growth factor (FGF) -2. Inhibition of FGF-2 or FGF
      receptors (FGFRs) signaling abolishes these effects. FGFRs activate SRC in cancer
      cells and inhibition or silencing of SRC in cancer cells, but not in fibroblasts,
      prevents fibroblasts-mediated effects. Using an RGD-based integrin antagonist and
      function-blocking antibodies we demonstrate that cancer cell adhesion to
      fibroblasts requires integrin alphavbeta5. Taken together, these results
      demonstrate that fibroblasts induce cell-contact-dependent colorectal cancer cell
      migration and invasion under 2D and 3D conditions in vitro through fibroblast
      cell surface-associated FGF-2, FGF receptor-mediated SRC activation and
      alphavbeta5 integrin-dependent cancer cell adhesion to fibroblasts. The FGF-2
      FGFRs-SRC-alphavbeta5 integrin loop might be explored as candidate therapeutic
      target to block colorectal cancer invasion. 

PMID- 25973545
TI  - Attentional Bias Through Oscillatory Coherence Between Excitatory Activity and
      Inhibitory Minima.
AB  - An implementation of attentional bias is presented for a network model that
      couples excitatory and inhibitory oscillatory units in a manner that is inspired
      by the mechanisms that generate cortical gamma oscillations. Attentional biases
      are implemented as oscillatory coherences between excitatory units that encode
      the spatial location or features of the target and the pool of inhibitory units.
      This form of attentional bias is motivated by neurophysiological findings that
      relate selective attention to spike field coherence. Including also pattern
      recognition mechanisms, we demonstrate how this implementation of attentional
      bias leads to selection of an attentional target while suppressing distracters
      for cases of spatial and feature-based attention. With respect to
      neurophysiological observations, we argue that the recently found positive
      correlation between high firing rates and strong gamma locking with attention
      (Vinck, Womelsdorf, Buffalo, Desimone, & Fries, 2013) may point to an essential
      mechanism of the brain's attentional selection and suppression processes.

PMID- 25973546
TI  - On the Spike Train Variability Characterized by Variance-to-Mean Power
      Relationship.
AB  - We propose a statistical method for modeling the non-Poisson variability of spike
      trains observed in a wide range of brain regions. Central to our approach is the
      assumption that the variance and the mean of interspike intervals are related by
      a power function characterized by two parameters: the scale factor and exponent.
      It is shown that this single assumption allows the variability of spike trains to
      have an arbitrary scale and various dependencies on the firing rate in the spike
      count statistics, as well as in the interval statistics, depending on the two
      parameters of the power function. We also propose a statistical model for spike
      trains that exhibits the variance-to-mean power relationship. Based on this, a
      maximum likelihood method is developed for inferring the parameters from rate
      modulated spike trains. The proposed method is illustrated on simulated and
      experimental spike trains. 

PMID- 25973547
TI  - Unifying Blind Separation and Clustering for Resting-State EEG/MEG Functional
      Connectivity Analysis.
AB  - Unsupervised analysis of the dynamics (nonstationarity) of functional brain
      connectivity during rest has recently received a lot of attention in the
      neuroimaging and neuroengineering communities. Most studies have used functional
      magnetic resonance imaging, but electroencephalography (EEG) and
      magnetoencephalography (MEG) also hold great promise for analyzing nonstationary
      functional connectivity with high temporal resolution. Previous EEG/MEG analyses
      divided the problem into two consecutive stages: the separation of neural sources
      and then the connectivity analysis of the separated sources. Such nonoptimal
      division into two stages may bias the result because of the different prior
      assumptions made about the data in the two stages. We propose a unified method
      for separating EEG/MEG sources and learning their functional connectivity
      (coactivation) patterns. We combine blind source separation (BSS) with
      unsupervised clustering of the activity levels of the sources in a single
      probabilistic model. A BSS is performed on the Hilbert transforms of band-limited
      EEG/MEG signals, and coactivation patterns are learned by a mixture model of
      source envelopes. Simulation studies show that the unified approach often
      outperforms conventional two-stage methods, indicating further the benefit of
      using Hilbert transforms to deal with oscillatory sources. Experiments on resting
      state EEG data, acquired in conjunction with a cued motor imagery or nonimagery
      task, also show that the states (clusters) obtained by the proposed method often
      correlate better with physiologically meaningful quantities than those obtained
      by a two-stage method. 

PMID- 25973548
TI  - A Hebbian/Anti-Hebbian Neural Network for Linear Subspace Learning: A Derivation
      from Multidimensional Scaling of Streaming Data.
AB  - Neural network models of early sensory processing typically reduce the
      dimensionality of streaming input data. Such networks learn the principal
      subspace, in the sense of principal component analysis, by adjusting synaptic
      weights according to activity-dependent learning rules. When derived from a
      principled cost function, these rules are nonlocal and hence biologically
      implausible. At the same time, biologically plausible local rules have been
      postulated rather than derived from a principled cost function. Here, to bridge
      this gap, we derive a biologically plausible network for subspace learning on
      streaming data by minimizing a principled cost function. In a departure from
      previous work, where cost was quantified by the representation, or
      reconstruction, error, we adopt a multidimensional scaling cost function for
      streaming data. The resulting algorithm relies only on biologically plausible
      Hebbian and anti-Hebbian local learning rules. In a stochastic setting, synaptic
      weights converge to a stationary state, which projects the input data onto the
      principal subspace. If the data are generated by a nonstationary distribution,
      the network can track the principal subspace. Thus, our result makes a step
      toward an algorithmic theory of neural computation. 

PMID- 25973550
TI  - Learning Slowness in a Sparse Model of Invariant Feature Detection.
AB  - Primary visual cortical complex cells are thought to serve as invariant feature
      detectors and to provide input to higher cortical areas. We propose a single
      model for learning the connectivity required by complex cells that integrates two
      factors that have been hypothesized to play a role in the development of
      invariant feature detectors: temporal slowness and sparsity. This model, the
      generative adaptive subspace self-organizing map (GASSOM), extends Kohonen's
      adaptive subspace self-organizing map (ASSOM) with a generative model of the
      input. Each observation is assumed to be generated by one among many nodes in the
      network, each being associated with a different subspace in the space of all
      observations. The generating nodes evolve according to a first-order Markov chain
      and generate inputs that lie close to the associated subspace. This model differs
      from prior approaches in that temporal slowness is not an externally imposed
      criterion to be maximized during learning but, rather, an emergent property of
      the model structure as it seeks a good model of the input statistics. Unlike the
      ASSOM, the GASSOM does not require an explicit segmentation of the input training
      vectors into separate episodes. This enables us to apply this model to an
      unlabeled naturalistic image sequence generated by a realistic eye movement
      model. We show that the emergence of temporal slowness within the model improves
      the invariance of feature detectors trained on this input. 

PMID- 25973549
TI  - Clusterless Decoding of Position from Multiunit Activity Using a Marked Point
      Process Filter.
AB  - Point process filters have been applied successfully to decode neural signals and
      track neural dynamics. Traditionally these methods assume that multiunit spiking
      activity has already been correctly spike-sorted. As a result, these methods are
      not appropriate for situations where sorting cannot be performed with high
      precision, such as real-time decoding for brain-computer interfaces. Because the
      unsupervised spike-sorting problem remains unsolved, we took an alternative
      approach that takes advantage of recent insights into clusterless decoding. Here
      we present a new point process decoding algorithm that does not require multiunit
      signals to be sorted into individual units. We use the theory of marked point
      processes to construct a function that characterizes the relationship between a
      covariate of interest (in this case, the location of a rat on a track) and
      features of the spike waveforms. In our example, we use tetrode recordings, and
      the marks represent a four-dimensional vector of the maximum amplitudes of the
      spike waveform on each of the four electrodes. In general, the marks may
      represent any features of the spike waveform. We then use Bayes's rule to
      estimate spatial location from hippocampal neural activity. We validate our
      approach with a simulation study and experimental data recorded in the
      hippocampus of a rat moving through a linear environment. Our decoding algorithm
      accurately reconstructs the rat's position from unsorted multiunit spiking
      activity. We then compare the quality of our decoding algorithm to that of a
      traditional spike-sorting and decoding algorithm. Our analyses show that the
      proposed decoding algorithm performs equivalent to or better than algorithms
      based on sorted single-unit activity. These results provide a path toward
      accurate real-time decoding of spiking patterns that could be used to carry out
      content-specific manipulations of population activity in hippocampus or elsewhere
      in the brain. 

PMID- 25973551
TI  - Comments and Correction on "U-Processes and Preference Learning" (Neural
      Computation Vol. 26, pp. 2896-2924, 2014).
AB  - This note corrects an error in the proof of corollary 1 of Li et al. ( 2014 ).
      The original claim of the contraction principle in appendix D of Li et al. no
      longer holds. 

PMID- 25973552
TI  - NMR Study of Ion Dynamics and Charge Storage in Ionic Liquid Supercapacitors.
AB  - Ionic liquids are emerging as promising new electrolytes for supercapacitors.
      While their higher operating voltages allow the storage of more energy than
      organic electrolytes, they cannot currently compete in terms of power
      performance. More fundamental studies of the mechanism and dynamics of charge
      storage are required to facilitate the development and application of these
      materials. Here we demonstrate the application of nuclear magnetic resonance
      spectroscopy to study the structure and dynamics of ionic liquids confined in
      porous carbon electrodes. The measurements reveal that ionic liquids
      spontaneously wet the carbon micropores in the absence of any applied potential
      and that on application of a potential supercapacitor charging takes place by
      adsorption of counterions and desorption of co-ions from the pores. We find that
      adsorption and desorption of anions surprisingly plays a more dominant role than
      that of the cations. Having elucidated the charging mechanism, we go on to study
      the factors that affect the rate of ionic diffusion in the carbon micropores in
      an effort to understand supercapacitor charging dynamics. We show that the line
      shape of the resonance arising from adsorbed ions is a sensitive probe of their
      effective diffusion rate, which is found to depend on the ionic liquid studied,
      as well as the presence of any solvent additives. Taken as whole, our NMR
      measurements allow us to rationalize the power performances of different
      electrolytes in supercapacitors. 

PMID- 25973553
TI  - Dual antiplatelet therapy following drug-eluting stent implantation: how long is
      long enough?
AB  - A period of dual antiplatelet therapy (DAPT) is mandatory after drug-eluting
      stent (DES) implantation to reduce the risk of stent thrombosis as a consequence
      of inflammation during the healing process. DAPT is also claimed to be associated
      with other benefits beyond this, including a reduction in ischemic events and
      improvements in clinical outcomes. A number of studies have investigated the
      feasibility of shortened DAPT in a bid to maximize benefits, while reducing
      adverse events; however, there are recent data to suggest that prolongation of
      DAPT may be associated with additional benefits at the risk of increased bleeding
      complications. On the basis of currently available evidence, we believe that all
      patients should be treated with DAPT for a minimum of 6 months after drug-eluting
      stent (DES) implantation. However, the decision to prolong therapy beyond this
      should be made on an individual basis, taking into account the potential benefits
      against specific risk factors for subsequent adverse events. 

PMID- 25973555
TI  - Local de-condensation of double-stranded DNA in oppositely charged
      polyelectrolyte as induced by spermidine.
AB  - How polyamines such as spermidine cooperate with histone to condense and de
      condense DNA during transcription has not been clarified. In this work, using the
      complex of DNA and poly(L-lysine) (PLL) at +/- ratio of 0.5 as a model of
      nucleosome, we monitored the de-condensation of DNA in the presence of
      spermidine. As revealed by the results from atomic force microscopy and time
      resolved laser light scattering, spermidine was able to transform the spherical
      complex into a core-shelled structure, with the hard core being the DNA-PLL
      complex and the soft shell being DNA and spermidine. The soft shell evolved into
      a coiled DNA conformation with time. Such a local de-condensation process should
      be helpful in understanding the DNA transcription and cell division process in
      vivo.

PMID- 25973556
TI  - The evolution of radiotherapy techniques in the management of prostate cancer.

PMID- 25973554
TI  - Impact of a Yoga Intervention on Physical Activity, Self-Efficacy, and Motivation
      in Women with PTSD Symptoms.
AB  - BACKGROUND: Studies using yoga have demonstrated initial efficacy for treating
      symptoms across anxiety disorders, including posttraumatic stress disorder.
      OBJECTIVE: Understanding how interventions influence participants' physical
      activity and what determinants affect continued physical activity behavior change
      is important because maintenance of the behavior may be critical to continued
      mental health gains and symptom reduction. METHODS: This study investigated
      change in physical activity and possible psychological mechanisms of physical
      activity behavior change, including self-efficacy and regulatory motivation, in a
      randomized controlled trial of yoga for women with post-traumatic stress disorder
      symptoms (n=38). RESULTS: Growth curve modeling results showed no significant
      changes in physical activity or self-efficacy for either group, whereas external
      motivation decreased significantly in the yoga group but not in the control
      group. CONCLUSIONS: Investigators of future yoga interventions may want to focus
      on increasing self-efficacy and internal regulatory motivation, so that physical
      activity and resultant symptom relief can be maintained.

PMID- 25973557
TI  - Effects of Resistance Training on Obese Adolescents.
AB  - PURPOSE: The effects of resistance training (RT) alone upon endothelial function,
      metabolic and hemodynamic profiles, physical fitness, body composition, and
      inflammatory biomarkers in nondiabetic obese adolescents were investigated.
      METHODS: Adolescents were assigned into nonobese control (CG, n = 20; 14.7 +/-
      1.4 yr) and obese (OB, n = 24; 14.1 +/- 1.0 yr) groups. Muscle and skin
      endothelial reactivity, body composition, at-office and 24-h ambulatory blood
      pressure, metabolic profile, adipocytokines, aerobic and strength fitness were
      assessed before and after 12 wk of RT (CG, only at admission). RESULTS: After RT,
      body mass did not change in OB, but significant reductions in body fat (1.6%; P =
      0.01), waist circumference (2.9%; P < 0.001), waist-to-hip ratio (3.3%; P <
      0.001), homeostasis model assessment for insulin resistance (15.4%; P = 0.02),
      endothelin-1 (14.2%; P = 0.04), and fibrinogen (6.9%; P = 0.03) were found. Both
      at-office and ambulatory blood pressure decreased, whereas skin endothelium
      dependent vasodilation (32%; P = 0.02), VO2 (14.3%; P = 0.04), and HR (5.3%; P =
      0.04) during submaximal exercise and isokinetic strength (extension, 21.3%;
      flexion, 29.9%; P < 0.0001) increased. Forearm vascular conductance increased at
      rest (28.1%; P = 0.03) and during postocclusive reactive hyperemia (25.2%; P =
      0.02). After RT differences between CG and OB at admission were no longer
      detected for most outcomes. CONCLUSIONS: RT alone improved endothelial function,
      hemodynamic and metabolic profiles, body composition, and physical fitness in
      nondiabetic obese adolescents regardless of changes in body mass.

PMID- 25973558
TI  - Physical Activity throughout Adolescence and Cognitive Performance at 18 Years of
      Age.
AB  - PURPOSE: This study aimed to examine the prospective associations of physical
      activity at 11, 15, and 18 yr of age with cognitive performance in young
      adulthood in a large birth cohort study from Brazil. METHODS: Participants were
      part of a large birth cohort study in Pelotas, Brazil (n = 3235 participants).
      Physical activity was self-reported at 11, 15, and 18 yr and was also objectively
      measured at 18 yr. Cognitive performance was assessed using an adapted Brazilian
      version of the short form of the Wechsler Adult Intelligence Scale at 18 yr.
      RESULTS: At 11 yr, participants in the middle tertile of self-reported physical
      activity presented a significantly higher cognitive performance score as compared
      with the lowest tertile. Physical activity at 15 yr of age was unrelated to
      cognitive performance at 18 yr. Self-reported physical activity was cross
      sectionally positively associated with cognitive performance at 18 yr (P <
      0.001). Data from objectively measured physical activity at 18 yr showed that
      those in the highest moderate-to-vigorous physical activity tertile presented
      lower cognitive performance scores at 18 yr as compared with those in the lowest
      tertile (-2.59; 95% confidence interval (CI), -3.41 to -1.48). Analyses on
      changes in tertiles of physical activity showed that maintaining an intermediate
      physical activity level from 11 to 18 yr and from 15 to 18 yr was associated with
      a higher cognitive performance score of 2.31 (95% CI, 0.71-3.91) and 1.84 score
      (95% CI, 0.25-3.42), respectively. CONCLUSIONS: Physical activity throughout
      adolescence is associated with cognitive performance before adulthood.
      Adolescents who are active at moderate levels, specifically those who maintain
      these levels of physical activity, tend to show higher cognitive performance.
      However, high levels of physical activity might impair cognitive performance.

PMID- 25973559
TI  - Evolution of Facial Aesthetic Treatment Over Five or More Years: A Retrospective
      Cross-sectional Analysis of Continuous OnabotulinumtoxinA Treatment.
AB  - BACKGROUND: Little information exists on how facial aesthetic treatments are
      incorporated into aesthetic regimens. OBJECTIVE: Assess the evolution of facial
      aesthetic treatments in patients receiving long-term continuous
      onabotulinumtoxinA treatment. METHODS: This international retrospective chart
      review included patients with >=5 years of continuous onabotulinumtoxinA
      treatments including >=1 glabellar lines treatment/year. Charts were reviewed for
      facial areas treated, number of treatments, doses/treatment visit, concomitant
      aesthetic procedures, and onabotulinumtoxinA-related adverse events. RESULTS:
      Data were collected from 5,112 onabotulinumtoxinA treatment sessions for 194
      patients over an average of 9.1 years. Dosing was relatively stable over time;
      however, interinjection intervals increased. Glabellar lines' treatment
      temporally preceded crow's feet lines and forehead lines' treatment. A majority
      of patients (85%) also received treatment with fillers. Cumulative increases in
      onabotulinumtoxinA treatments occurred over time and by facial area corresponding
      with increases in treatments with injectable fillers, energy-based devices, and
      prescription topical creams. The longer the patients were treated, the younger
      they perceived themselves to look. Rates of adverse events were low. CONCLUSION:
      OnabotulinumtoxinA treatment evolved over time, coinciding with growth of the
      facial aesthetics market. Additional treatment modalities were added as
      complements to onabotulinumtoxinA. Long-term continuous onabotulinumtoxinA
      injections are an important component of contemporary facial aesthetic treatment
      regimens.

PMID- 25973560
TI  - Repair of adjacent ocular defects.

PMID- 25973561
TI  - Erk1/2 activation in stromal fibroblasts from sporadic basal cell carcinomas.
AB  - BACKGROUND: Constitutive activation of the Erk pathway can lead to oncogenic
      transformation. However, the Erk pathway is not activated in human basal cell
      carcinomas (BCCs); although in animal models, this seems to be important.
      OBJECTIVE: To help understand the role of Erk activity in BCC formation.
      MATERIALS AND METHODS: The authors assayed the specific levels of phosphorylated
      Erk by immunohistochemistry in BCCs and normal skin biopsies. They have also
      analyzed Erk activation by immunoblot in fibroblasts isolated from BCC. RESULTS:
      By immunohistochemical analysis, the authors have observed that 10 of BCCs (56%)
      did not show phosphor-Erk staining in tumor masses and 7 (40%) showed a gradient
      staining exhibiting phospho-Erk only in the epidermal side of tumor masses.
      Remarkably, 15 BCC samples (83%) showed phospho-Erk accumulation in stroma. Six
      of the 9 independent cultures of dermal fibroblasts isolated from BCC maintained
      Erk activation "in vitro." CONCLUSION: The authors propose that there is a
      specific cell-type regulation of Erk activity in BCC, and this feature may be
      relevant during BCC formation. Stroma region from BCCs showed Erk activation and
      reduced proliferation. Conversely, Erk activation is barely detectable in
      proliferative BCCs.

PMID- 25973562
TI  - A new method for using radiopaque sclerosing foam to treat venous malformations.
AB  - BACKGROUND: Sclerosing foam is recommended to treat venous malformations (VMs).
      However, determining the precise dosage for satisfactory efficacy and few side
      effects are still challenging. OBJECTIVE: To develop a new method of preparing
      sclerosing foam by adding contrast agent to treat patients with VMs visibly and
      precisely under radiologic guidance. MATERIALS AND METHODS: Sclerosant
      (polidocanol) and contrast agent (iopromide) were mixed to prepare a new
      sclerosing foam according to Tessari method, and different ratios of the 2
      materials were used to study the stability (half-life) of the produced foams. X
      ray absorption of the radiopaque foams was observed during patient treatment with
      digital subtraction angiography (DSA). RESULTS: The foams generated with the new
      method demonstrated a high x-ray absorption under DSA. The foam half-life among
      groups varied. The ratio of iopromide/polidocanol at 1:2 had a significantly
      longer half-life than the 1:1 or polidocanol-only group. The 1:2 group had a
      relative high x-ray absorption and was radiopaque to allow visualization of the
      sclerosing foam and lesion with DSA. CONCLUSION: Mixing contrast agent with
      sclerosant to prepare radiopaque foams is a new method for treating complex VMs
      with DSA, and a ratio of 1:2 is recommend for polidocanol and iopromide.

PMID- 25973563
TI  - Impact of Postreconstitution Room Temperature Storage on the Efficacy of
      IncobotulinumtoxinA Treatment of Dynamic Lateral Canthus Lines.
AB  - BACKGROUND: The efficacy of botulinum neurotoxin type A after prolonged storage
      at room temperature is currently unknown. This randomized, double-blinded, split
      face study investigated the impact of postreconstitution 25 degrees C storage for
      1 week on the clinical efficacy of incobotulinumtoxinA in the treatment of
      lateral canthus lines. PATIENTS AND METHODS: Twenty-one participants with at
      least mild to moderate crow's feet at maximum contraction on the Crow's Feet
      Grading Scale (CFGS) underwent injection to each lateral canthus area with 10 U
      of freshly reconstituted and room temperature-stored product and followed for 4
      months. Responders were defined as those demonstrating at least a 1-point
      improvement on their CFGS score. RESULTS: At each visit (2 weeks and 1, 2, 3, and
      4 months), there was no statistical difference in the rate of responders between
      the fresh and the stored products. In addition, the percentage of responders
      displaying a 2-point versus a 1-point improvement and response longevity did not
      statistically differ between both products for the entire 4-month study duration.
      CONCLUSION: Prolonged storage of incobotulinumtoxinA at room temperature does not
      appear to significantly alter its efficacy or longevity in the treatment of
      dynamic lateral canthus lines.

PMID- 25973564
TI  - A novel facial rejuvenation treatment using pneumatic injection of non-cross
      linked hyaluronic acid and hypertonic glucose solution.

PMID- 25973565
TI  - Does cortisol influence core executive functions? A meta-analysis of acute
      cortisol administration effects on working memory, inhibition, and set-shifting.
AB  - The hormone cortisol is often believed to play a pivotal role in the effects of
      stress on human cognition. This meta-analysis is an attempt to determine the
      effects of acute cortisol administration on core executive functions. Drawing on
      both rodent and stress literatures, we hypothesized that acute cortisol
      administration would impair working memory and set-shifting but enhance
      inhibition. Additionally, because cortisol is thought to exert different
      nongenomic (rapid) and genomic (slow) effects, we further hypothesized that the
      effects of cortisol would differ as a function of the delay between cortisol
      administration and cognitive testing. Although the overall analyses were
      nonsignificant, after separating the rapid, nongenomic effects of cortisol from
      the slower, genomic effects of cortisol, the rapid effects of cortisol enhanced
      response inhibition, g+ = 0.113, p=.016, but impaired working memory, g+ = 
      0.315, p=.008, although these effects reversed over time. Contrary to our
      hypotheses, there was no effect of cortisol administration on set-shifting. Thus,
      although we did not find support for the idea that increases in cortisol
      influence set-shifting, we found that acute increases in cortisol exert
      differential effects on working memory and inhibition over time.

PMID- 25973566
TI  - Relationship between thyroid-stimulating hormone levels and risk of depression
      among the general population with normal free T4 levels.
AB  - OBJECTIVE: This study assessed the relationship between thyroid-stimulating
      hormone (TSH) level and risk of depressive symptom in a population with no
      clinical or laboratory evidence of thyroid dysfunction. METHODS: This
      retrospective cohort study included 13,017 subjects (7913 males and 5104
      females), 17-84 years of age, who underwent health examinations at the hospital.
      Subjects had a Beck Depression Inventory (BDI) total score of <=9 and fell within
      the normal range of free T4 levels at baseline. The association between gender
      specific serum TSH tertile at baseline and the development of clinically
      significant depressive symptom (i.e., >=19 BDI total score) on the follow-up
      visit was evaluated using the Cox proportional hazards model, with adjustment for
      demographic and life style factors. RESULTS: The risk of depressive symptom was
      increased among subjects with the highest tertile TSH level (adjusted hazard
      ratio [HR], 2.236; 95% confidence interval [CI], 1.443-3.466; p<0.001) as
      compared with subjects with the lowest tertile in females, but not in males. Even
      among patients with normal TSH levels, females in the lowest-normal TSH tertile
      had a higher risk of depressive symptoms (adjusted HR, 2.279; 95% CI, 1.456
      3.567; p<0.001) than did those in the highest tertile. The TSH level as a
      continuous variable significantly predicted the depressive symptoms in females
      (adjusted HR, 1.402; 95% CI, 1.002-1.812; p=0.027). CONCLUSIONS: Our finding
      suggests that suboptimal thyroid function increases vulnerability to the
      occurrence of depressive symptom and represents a modifiable risk factor for
      depression in females.

PMID- 25973567
TI  - Prereproductive stress in adolescent female rats affects behavior and
      corticosterone levels in second-generation offspring.
AB  - Human and animal studies indicate that vulnerability to stress may be heritable.
      We have previously shown that chronic, mild prereproductive stress (PRS) in
      adolescent female rats affects behavior and corticotropin releasing factor 1
      (CRF1) expression in the brain of first-generation (F1) offspring. Here, we
      investigated the effects of PRS on anxiogenic behavior and CRF1 expression in
      male and female second-generation (F2) offspring. Furthermore, we assessed levels
      of the stress hormone corticosterone (CORT), a direct marker of hypothalamic
      pituitary-adrenal (HPA) axis function, in PRS females and their F1 and F2
      progeny. F2 offspring demonstrated decreased CRF1 mRNA expression at birth, and
      alterations in anxiogenic behavior in adulthood. CORT levels were elevated in PRS
      females and in their F1 female, but not male, offspring. In F2, CORT levels in
      PRS offspring also varied in a sex-dependent manner. These findings indicate that
      PRS in adolescent females leads to behavioral alterations that extend to second
      generation offspring, and has transgenerational effects on endocrine function.
      Together with our previous findings, these data indicate that PRS to adolescent
      females affects behavior and HPA axis function across three generations, and
      highlight the importance of examining the transgenerational effects of stress in
      both male and female offspring. 

PMID- 25973568
TI  - The Impact of a Portable Metabolic Measurement Device on Gait Characteristics of
      Older Adults With Mobility Limitations.
AB  - BACKGROUND AND PURPOSE: Increased carriage loads have been found to alter gait
      biomechanics in young healthy adults and military personnel; however, less is
      known regarding the influence of added carriage load on the gait characteristics
      of older adults-especially those with mobility limitations. The purpose of this
      study was to examine spatial and temporal gait characteristics during
      instrumented and noninstrumented overground walking in a sample of older adults
      with slow gait. METHODS: Forty older adults with slow gait completed 2 bouts of
      walking (instrumented and noninstrumented) over a computerized walkway during 1
      clinic visit. Mean spatial-temporal characteristics, gait variability, and gait
      speed over 8 passes were recorded. Paired t tests and intraclass correlation
      coefficients were used to quantify differences. RESULTS AND DISCUSSION: Nine of
      the 10 gait variables did not differ statistically between instrumented and
      noninstrumented gait (P < .05). Intraclass correlation coefficients (ICCs) for
      mean gait characteristics were excellent (range ICC = 0.94-0.98; 95% confidence
      interval = 0.89-0.99), and for gait variability ranged from fair to excellent
      (range ICC = 0.56-0.79; 95% confidence interval = 0.28-0.89). Our study was able
      to demonstrate no significant impact of instrumentation on gait characteristics
      in a sample of older adults with slow gait. CONCLUSION: Our findings begin to
      fill in the gaps in the literature regarding the impact of added carriage loads
      on more vulnerable populations and lend support for the use of similar weighted
      metabolic devices as a component of gait assessment in older adults with
      confidence that the additional carriage-load will not significantly impact
      concurrent measures of gait.

PMID- 25973570
TI  - Baculoviral p94 homologs encoded in Cotesia plutellae bracovirus suppress both
      immunity and development of the diamondback moth, Plutellae xylostella.
AB  - Polydnaviruses (PDVs) are a group of insect DNA viruses, which exhibit a mutual
      symbiotic relationship with their specific host wasps. Moreover, most
      encapsidated genes identified so far in PDVs share homologies with insect
      originated genes, but not with virus-originated genes. In the meantime, PDVs
      associated with 2 wasp genera Cotesia and Glytapanteles encode some genes
      presumably originated from other viruses. Cotesia plutellae bracovirus (CpBV)
      encodes 4 genes homologous to baculoviral p94: CpBV-E94k1, CpBV-E94k2, CpBV
      E94k3, and CpBV-E94k4. This study was conducted to predict the origin of CpBV
      E94ks by comparing their sequences with those of baculoviral orthologs and to
      determine the physiological functions by their transient expressions in
      nonparasitized larvae and subsequent specific RNA interference. Our phylogenetic
      analysis indicated that CpBV-E94ks were clustered with other E94ks originated
      from different PDVs and shared high similarity with betabaculoviral p94s. These 4
      CpBV genes were expressed during most developmental stages of the larvae of
      Plutella xylostella parasitized by C. plutellae. Expression of these 4 E94ks was
      mainly detected in hemocytes and fat body. Subsequent functional analysis by in
      vivo transient expression showed that all 4 viral genes significantly inhibited
      both host immune and developmental processes. These results suggest that CpBV
      E94ks share an origin with betabaculoviral p94s and play parasitic roles in
      suppressing host immune and developmental processes. 

PMID- 25973569
TI  - Does Age Affect the Relationship Between Pain and Disability? A Descriptive Study
      in Individuals Suffering From Chronic Low Back Pain.
AB  - BACKGROUND: Previous studies have revealed a weak to moderate relationship
      between pain and disability in individuals suffering from low back pain (LBP).
      However, to our knowledge, no studies have evaluated if this relationship is
      different between young and older adults. PURPOSE: The objective of this
      descriptive, cross-sectional study was to determine whether the relationship
      between LBP intensity and physical disability is different between young and
      older adults. METHODS: Pain intensity (measured with a visual analog scale) and
      physical disability scores (measured with the Oswestry Disability Index) were
      collected from the medical files of 164 patients with LBP. Separate Pearson
      correlation coefficients were calculated between these 2 variables for young
      (mean age 40 +/- 6 years, n = 82) and older (62 +/- 9 years, n = 82) individuals
      and a Fisher r-to-z transformation was used to test for group differences in the
      strength of the relationship. Linear regression analyses were also performed to
      determine whether the slope of the association was different between the 2
      groups. RESULTS: A significant and positive association was found between pain
      intensity and disability for both young and older individuals. However, the
      correlation was stronger in the young group (r = 0.66; P < .01) than in the older
      group (r = 0.44; P < .01) (Fisher Z = 2.03; P < .05). The linear regression model
      also revealed that the slope of the relationship was steeper in the young group
      (P < .05). CONCLUSION: Although both young and older individuals showed a
      significant association between pain intensity and disability, the relationship
      between these 2 variables was more tenuous in older individuals than in young
      patients. Future research is essential to identify the factors underlying this
      age-related difference.

PMID- 25973572
TI  - Slow crystallisation of a monodisperse foam stabilised against coarsening.
AB  - The evolution of a three-dimensional monodisperse foam was investigated using X
      ray tomography over the course of seven days. The coarsening of the sample was
      inhibited through the use of perfluorohexane gas. The internal configuration of
      bubbles is seen to change markedly, evolving from a disordered arrangement
      towards a more ordered state. We chart this ordering process through the use of
      the coordination number, the bond orientational order parameter (BOOP) and the
      translational order parameter. 

PMID- 25973571
TI  - Multivalent aptamer/gold nanoparticle-modified graphene oxide for mass
      spectrometry-based tumor tissue imaging.
AB  - The protein mucin1 (MUC1) is an attractive target for cancer biomarkers because
      it is overexpressed in most adenocarcinomas. In this study, we exploited a MUC1
      binding aptamer (AptMUC1) as a targeting agent for nanoparticle-based imaging
      systems coupled with laser desorption/ionization mass spectrometry (LDI-MS). We
      found that AptMUC1-conjugated gold nanoparticles immobilized, through hydrophobic
      and pi-pi interactions, on graphene oxide (AptMUC1-Au NPs/GO) bound effectively
      to MUC1 units on tumor cell membranes. The ultrahigh density and high flexibility
      of AptMUC1 on the GO surface enhanced the platform's cooperative and multivalent
      binding affinity for MUC1 on cell membranes. After we had labeled MUC1
      overexpressing MCF-7 cells (human breast adenocarcinoma cell line) with AptMUC1
      Au NPs/GO, we used LDI-MS to monitor Au cluster ions ([Aun](+); n = 1-3),
      resulting in the detection of as few as 100 MCF-7 cells. We also employed this
      AptMUC1-Au NPs/GO-LDI-MS system to analyze four different MUC1 expression cell
      lines. In addition, the AptMUC1-Au NPs/GO platform could be used further as a
      labeling agent for tumor tissue imaging when coupled with LDI-MS. Thus, Apt-Au
      NPs/GO can function as a highly amplified signal transducer through the formation
      of large Au clusters ions during LDI-MS analysis. 

PMID- 25973574
TI  - Clinical cardiac structural anatomy reconstructed within the cardiac contour
      using multidetector-row computed tomography: The arrangement and location of the
      cardiac valves.
AB  - It is essential for the interventional cardiologist to have in-depth anatomical
      information about the three-dimensional arrangement and location of the cardiac
      valves relative to the various projections of the cardiac contour as revealed
      fluoroscopically. Multidetector-row computed tomography is useful for providing
      information about the three-dimensional arrangements of each structure. This
      article presents cardiac structural images, focusing on the arrangement and
      location of the cardiac valves, which were reconstructed with the cardiac contour
      and surrounding structures using multidetector-row computed tomography. We
      discuss the clinical implications of the findings. We hope these images will
      serve as a bridge between cardiology, radiology, and anatomy, and will prompt
      scientists in the field of cardiology to integrate their accumulated insights
      into three-dimensional clinical images of the living heart.

PMID- 25973573
TI  - Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co
      chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained
      approaches.
AB  - The iron-sulfur protein 1 (Isu1) and the J-type co-chaperone Jac1 from yeast are
      part of a huge ATP-dependent system, and both interact with Hsp70 chaperones.
      Interaction of Isu1 and Jac1 is a part of the iron-sulfur cluster biogenesis
      system in mitochondria. In this study, the structure and dynamics of the yeast
      Isu1-Jac1 complex has been modeled. First, the complete structure of Isu1 was
      obtained by homology modeling using the I-TASSER server and YASARA software and
      thereafter tested for stability in the all-atom force field AMBER. Then, the
      known experimental structure of Jac1 was adopted to obtain initial models of the
      Isu1-Jac1 complex by using the ZDOCK server for global and local docking and the
      AutoDock software for local docking. Three most probable models were subsequently
      subjected to the coarse-grained molecular dynamics simulations with the UNRES
      force field to obtain the final structures of the complex. In the most probable
      model, Isu1 binds to the left face of the Gamma-shaped Jac1 molecule by the beta
      sheet section of Isu1. Residues L105 , L109 , and Y163 of Jac1 have been assessed
      by mutation studies to be essential for binding (Ciesielski et al., J Mol Biol
      2012; 417:1-12). These residues were also found, by UNRES/molecular dynamics
      simulations, to be involved in strong interactions between Isu1 and Jac1 in the
      complex. Moreover, N(95), T(98), P(102), H(112), V(159), L(167), and A(170) of
      Jac1, not yet tested experimentally, were also found to be important in binding.

PMID- 25973576
TI  - Molecular mechanisms of amitraz mammalian toxicity: a comprehensive review of
      existing data.
AB  - Amitraz is a formamidine pesticide widely used as an insecticide and acaricide.
      Amitraz poisoning cases in humans and animals are still being described to date,
      which is a cause of concern for health authorities. Amitraz was reported not to
      pose unreasonable risks or adverse effects to humans or the environment unlike
      the other commercialized member of the formamidine family, chlordimeform, which
      was removed from the market because of carcinogenic effects in animal studies.
      Amitraz was classified as a nonquantifiable "Suggestive Evidence of
      Carcinogenicity" and not genotoxic, but recently, it has been reported that it
      could induce genotoxic effects. Moreover, ever since the previously published
      evaluations made by the Environmental Protection Agency (EPA) and the Joint
      Meeting of Pesticide Residues (JMPR) there have been new reported data on amitraz
      toxicity related to genotoxicity, oxidative stress, cell death, immunotoxicty,
      endocrine disruption, and developmental toxicity which indicate that the risk of
      this compound could be underestimated. Furthermore, there is missing information
      about the dose-response relationship for some mechanisms and toxic effects
      described for amitraz and its metabolites, the mechanism of action by which
      several toxic effects are produced, and amitraz pharmacokinetics on different
      species. According to this, the new information reported should be taken into
      account, and more studies should be performed to fill in the gaps of missing
      information for a complete hazard identification and therefore an exhaustive risk
      assessment of amitraz. This review is aimed at updating the current knowledge on
      molecular mechanisms of amitraz mammalian toxicity, pointing out the missing
      information, providing some possible explanation of the mechanism by which some
      toxic effects observed are produced, and suggesting future direction of its
      research. To our knowledge, this is the first review on the molecular mechanisms
      of amitraz toxicity.

PMID- 25973575
TI  - Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver
      specific miRNA-122 and sensitize monocytes to LPS.
AB  - Hepatocyte damage and inflammation in monocytes/macrophages are central to the
      pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of
      these processes. MiRNA-122 is abundantly expressed in hepatocytes while
      monocytes/macrophages have low levels. The role of exosomes in AH and possible
      cross talk between hepatocyte-derived exosomes and immune cells is not explored
      yet. Here, we show that the number of exosomes significantly increases in the
      sera of healthy individuals after alcohol binge drinking and in mice after binge
      or chronic alcohol consumption. Exosomes isolated from sera after alcohol
      consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122.
      Exosomes derived from ethanol-treated Huh7.5 cells were taken up by the
      recipients THP1 monocytes and horizontally transferred a mature form of liver
      specific miRNA-122. In vivo, liver mononuclear cells and Kupffer cells from
      alcohol-fed mice had increased miRNA-122 levels. In monocytes, miRNA-122
      transferred via exosomes inhibited the HO-1 pathway and sensitized to LPS
      stimulation and increased levels of pro-inflammatory cytokines. Finally,
      inflammatory effects of exosomes from ethanol-treated hepatocytes were prevented
      by using RNA interference via exosome-mediated delivery of a miRNA-122 inhibitor.
      These results demonstrate that first, exosomes mediate communication between
      hepatocytes and monocytes/macrophages and second, hepatocyte-derived miRNA-122
      can reprogram monocytes inducing sensitization to LPS. 

PMID- 25973578
TI  - Primary Surgery vs Chemoradiation Treatment of Advanced-Stage Hypopharyngeal
      Squamous Cell Carcinoma.
AB  - IMPORTANCE: There is no consensus whether primary surgery followed by either
      adjuvant radiotherapy (RT) or adjuvant chemoradiation (CRT) or definitive CRT
      should be the standard treatment approach to advanced-stage hypopharyngeal
      squamous cell carcinoma (HP SCC). OBJECTIVES: To determine survival outcomes for
      patients with advanced-stage HP SCC treated at a single institution with either
      primary surgery plus RT or CRT or definitive CRT. EVIDENCE AND DATA ACQUISITION:
      We conducted a retrospective analysis of prospectively collected medical records
      in an institutional database for patients with HP SCC newly diagnosed between
      January 1999 and April 2013. Overall survival (OS) and recurrence-free survival
      (RFS) were calculated and compared between treatment groups using the Kaplan
      Meier method, with multivariate Cox regression analysis used to control for
      demographic and clinicopathologic features. RESULTS: We identified 166
      consecutively treated patients, 90 of whom did not meet study criteria. Of the 76
      included patients, 48 (63%) had undergone definitive CRT, and 28 (37%) had
      undergone primary surgery with adjuvant RT or CRT. The groups were well balanced
      by age, smoking history, and alcohol use. Five-year OS and RFS for patients
      treated surgically were 66.3% and 53.6%, respectively; for patients treated with
      definitive CRT, OS and RFS were 41.3% and 34.5%, respectively. Multivariate Cox
      regression analysis showed that surgical management was associated with
      clinically improved OS (hazard ratio [HR], 4.78; 95% CI, 0.91-25.03; P = .06) and
      RFS (HR, 2.97; 95% CI, 0.76-11.53; P = .12), although the difference was not
      statistically significant. CONCLUSIONS AND RELEVANCE: Patients with advanced
      stage HP SCC treated surgically with adjuvant RT or CRT showed a trend toward
      clinically improved OS and RFS compared with patients treated with definitive
      CRT. However, the difference was not statistically significant, and further
      investigation with larger controlled trials using modern approaches should be
      undertaken to optimize the initial management of advanced-stage HP SCC.

PMID- 25973577
TI  - Comparison of Exome and Genome Sequencing Technologies for the Complete Capture
      of Protein-Coding Regions.
AB  - For next-generation sequencing technologies, sufficient base-pair coverage is the
      foremost requirement for the reliable detection of genomic variants. We
      investigated whether whole-genome sequencing (WGS) platforms offer improved
      coverage of coding regions compared with whole-exome sequencing (WES) platforms,
      and compared single-base coverage for a large set of exome and genome samples. We
      find that WES platforms have improved considerably in the last years, but at
      comparable sequencing depth, WGS outperforms WES in terms of covered coding
      regions. At higher sequencing depth (95x-160x), WES successfully captures 95% of
      the coding regions with a minimal coverage of 20x, compared with 98% for WGS at
      87-fold coverage. Three different assessments of sequence coverage bias showed
      consistent biases for WES but not for WGS. We found no clear differences for the
      technologies concerning their ability to achieve complete coverage of 2,759
      clinically relevant genes. We show that WES performs comparable to WGS in terms
      of covered bases if sequenced at two to three times higher coverage. This does,
      however, go at the cost of substantially more sequencing biases in WES
      approaches. Our findings will guide laboratories to make an informed decision on
      which sequencing platform and coverage to choose. 

PMID- 25973579
TI  - EMR Study and DFT-Assisted Identification of Transient Radicals in X-Irradiated
      Crystalline Sucrose.
AB  - Solid-state sucrose is a well-known dosimetric system, which is capable of
      reliable dose estimates only at a considerable time after exposure. Immediately
      after irradiation at room temperature, its electron paramagnetic resonance (EPR)
      spectrum is dominated by contributions from unstable radicals, which are studied
      here using continuous-wave EPR and electron-nuclear double resonance (ENDOR)
      spectroscopy. Four hyperfine tensors of proton couplings were determined,
      associated with two radical species, and subsequently compared to density
      functional theory calculation results, which led to the identification of the
      species with lower abundance (U2) as a radical formed by a H abstraction from C4.
      The more abundant center (U1) has not been definitively identified yet, but we
      present compelling evidence that it should be a C6 centered radical. Comparison
      of the simulated EPR spectra with all available data to the experimental ones
      suggests that the EPR spectrum of X-irradiated sucrose immediately after
      irradiation can now be almost entirely understood. 

PMID- 25973580
TI  - Electrocoagulation treatment of peat bog drainage water containing humic
      substances.
AB  - Electrocoagulation (EC) treatment of 100 mg/L synthetic wastewater (SWW)
      containing humic acids was optimized (achieving 90% CODMn and 80% DOC removal
      efficiencies), after which real peat bog drainage waters (PBDWs) from three
      northern Finnish peat bogs were also treated. High pollutant removal efficiencies
      were achieved: Ptot, TS, and color could be removed completely, while Ntot,
      CODMn, and DOC/TOC removal efficiencies were in the range of 33-41%, 75-90%, and
      62-75%, respectively. Al and Fe performed similarly as the anode material. Large
      scale experiments (1 m(3)) using cold (T = 10-11  degrees C) PBDWs were also
      conducted successfully, with optimal treatment times of 60-120 min (applying
      current densities of 60-75 A/m(2)). Residual values of Al and Fe (complete
      removal) were lower than their initial values in the EC-treated PBDWs.
      Electricity consumption and operational costs in optimum conditions were found to
      be low and similar for all the waters studied: 0.94 kWh/m(3) and 0.15 ?/m(3) for
      SWW and 0.35-0.70 kWh/m(3) and 0.06-0.12 ?/m(3) for the PBDWs (large-scale).
      Thus, e.g. solar cells could be considered as a power source for this EC
      application. In conclusion, EC treatment of PBDW containing humic substances was
      shown to be feasible. 

PMID- 25973581
TI  - Life cycle comparison of centralized wastewater treatment and urine source
      separation with struvite precipitation: Focus on urine nutrient management.
AB  - Alternative approaches to wastewater management including urine source separation
      have the potential to simultaneously improve multiple aspects of wastewater
      treatment, including reduced use of potable water for waste conveyance and
      improved contaminant removal, especially nutrients. In order to pursue such
      radical changes, system-level evaluations of urine source separation in community
      contexts are required. The focus of this life cycle assessment (LCA) is managing
      nutrients from urine produced in a residential setting with urine source
      separation and struvite precipitation, as compared with a centralized wastewater
      treatment approach. The life cycle impacts evaluated in this study pertain to
      construction of the urine source separation system and operation of drinking
      water treatment, decentralized urine treatment, and centralized wastewater
      treatment. System boundaries include fertilizer offsets resulting from the
      production of urine based struvite fertilizer. As calculated by the Tool for the
      Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI),
      urine source separation with MgO addition for subsequent struvite precipitation
      with high P recovery (Scenario B) has the smallest environmental cost relative to
      existing centralized wastewater treatment (Scenario A) and urine source
      separation with MgO and Na3PO4 addition for subsequent struvite precipitation
      with concurrent high P and N recovery (Scenario C). Preliminary economic
      evaluations show that the three urine management scenarios are relatively equal
      on a monetary basis (<13% difference). The impacts of each urine management
      scenario are most sensitive to the assumed urine composition, the selected urine
      storage time, and the assumed electricity required to treat influent urine and
      toilet water used to convey urine at the centralized wastewater treatment plant.
      The importance of full nutrient recovery from urine in combination with the
      substantial chemical inputs required for N recovery via struvite precipitation
      indicate the need for alternative methods of N recovery. 

PMID- 25973582
TI  - Emerging nitrogenous disinfection byproducts: Transformation of the antidiabetic
      drug metformin during chlorine disinfection of water.
AB  - As an environmental contaminant of anthropogenic origin metformin is present in
      the high ng/L- up to the low MUg/L-range in most surface waters. Residues of
      metformin may lead to the formation of disinfection by-products during chlorine
      disinfection, when these waters are used for drinking water production.
      Investigations on the underlying chemical processes occurring during treatment of
      metformin with sodium hypochlorite in aqueous medium led to the discovery of two
      hitherto unknown transformation products. Both substances were isolated and
      characterized by HPLC-DAD, GC-MS, HPLC-ESI-TOF, (1)H-NMR and single-crystal X-ray
      structure determination. The immediate major chlorination product is a cyclic
      dehydro-1,2,4-triazole-derivate of intense yellow color (Y; C4H6ClN5). It is a
      solid chlorimine of limited stability. Rapid formation was observed between 10 
      degrees C and 30  degrees C, as well as between pH 3 and pH 11, in both ultrapure
      and tap water, even at trace quantities of reactants (ng/L-range for metformin,
      mg/L-range for free chlorine). While Y is degraded within a few hours to days in
      the presence of light, elevated temperature, organic solvents and matrix
      constituents within tap water, a secondary degradation product was discovered,
      which is stable and colorless (C; C4H6ClN3). This chloroorganic nitrile has a low
      photolysis rate in ambient day light, while being resistant to heat and not
      readily degraded in the presence of organic solvents or in the tap water matrix.
      In addition, the formation of ammonia, dimethylamine and N,N-dimethylguanidine
      was verified by cation exchange chromatography. 

PMID- 25973584
TI  - Renal Denervation for the Treatment of Hypertension: Making a New Start, Getting
      It Right.

PMID- 25973583
TI  - Magnetic resonance temperature imaging-based quantification of blood flow-related
      energy losses.
AB  - This study presents a new approach for evaluating bioheat transfer equation
      (BHTE) models used in treatment planning, control and evaluation of all thermal
      therapies. First, 3D magnetic resonance temperature imaging (MRTI) data are used
      to quantify blood flow-related energy losses, including the effects of perfusion
      and convection. Second, this information is used to calculate parameters of a
      BHTE model: in this paper the widely used Pennes BHTE. As a self-consistency
      check, the BHTE parameters are utilized to predict the temperatures from which
      they were initially derived. The approach is evaluated with finite-difference
      simulations and implemented experimentally with focused ultrasound heating of an
      ex vivo porcine kidney perfused at 0, 20 and 40 ml/min (n = 4 each). The
      simulation results demonstrate accurate quantification of blood flow-related
      energy losses, except in regions of sharp blood flow discontinuities, where the
      transitions are spatially smoothed. The smoothed transitions propagate into
      estimates of the Pennes perfusion parameter but have limited effect on the
      accuracy of temperature predictions using these estimates. Longer acquisition
      time periods mitigate the effects of MRTI noise, but worsen the effect of flow
      discontinuities. For the no-flow kidney experiments the estimates of a uniform,
      constant Pennes perfusion parameter are approximately zero, and at 20 and 40
      ml/min the average estimates increase with flow rate to 3.0 and 4.2 kg/m(3) /s,
      respectively. When Pennes perfusion parameter values are allowed to vary
      spatially, but remain temporally constant, BHTE temperature predictions are more
      accurate than when using spatially uniform, constant Pennes perfusion values,
      with reductions in RMSE values of up to 79%. Locations with large estimated
      perfusion values correspond to high flow regions of the kidney observed in T1 
      weighted MR images. This novel, MRTI-based technique holds promise for improving
      understanding of thermal therapy biophysics and for evaluating biothermal models.

PMID- 25973585
TI  - High-Performance Polymer Solar Cells with Electrostatic Layer-by-Layer Self
      Assembled Conjugated Polyelectrolytes as the Cathode Interlayer.
AB  - An easy and efficient approach to achieve a large-area cathode interlayer with
      controlled film composition, uniformity, and thickness under a nanometer scale is
      reported by using an electrostatic layer-by-layer (eLbL) self-assembly process.
      The eLbL films provide a new means for preparing efficient interlayers for
      polymer solar cells (PSCs) and also represent a potential candidate for use in
      high-performance large-area PSC modules in the future. 

PMID- 25973586
TI  - The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable
      Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their
      Subsequent Merging into Factor VII.
AB  - Factor VII (FVII) deficiency is one of the two congenital coagulation disorders
      that was not discovered by the description of a new bleeding patient whose
      clotting pattern did not fit the blood coagulation knowledge of the time (the
      other is factor XIII deficiency). The existence of an additional factor capable
      of accelerating the conversion of prothrombin into thrombin was suspected before
      1951, the year in which the first family with FVII deficiency was discovered. As
      several investigators were involved in the discovery of FVII deficiency from both
      sides of the Atlantic, several different names were tentatively suggested to
      define this entity, namely stable factor (in contrast with labile factor or FV),
      cothromboplastin, proconvertin, serum prothrombin conversion accelerator,
      prothrombin acceleration, and autoprothrombin I. The last term was proposed by
      those who denied the existence of this new entity, which was instead considered
      to be a derivate of prothrombin activation, namely autoprothrombin. The
      description of several families, from all over the world, of the same defect,
      however clearly demonstrated the singularity of the condition. Factor VII was
      then proposed to define this protein. In subsequent years, several variants were
      described with peculiar reactivity toward tissue thromboplastins of different
      origin. Molecular biology techniques demonstrated several gene mutations, usually
      missense mutations, often involving exon 8 of the FVII gene. Later studies dealt
      with the relation of FVII with tissue factor and activated FVII (FVIIa). The
      evaluation of circulating FVIIa was made possible by the use of a truncated form
      of tissue factor, which is only sensitive to FVIIa present in the circulation.
      The development of FVII concentrates, both plasma derived and recombinant, has
      facilitated therapeutic management of FVII-deficient patients. The use of FVIIa
      concentrates was noted to be associated with the occasional occurrence of
      thrombotic events, mainly venous. Total or partial liver transplants have been
      performed with success in these patients and have "cured" their deficiencies.
      Prenatal diagnosis has also been performed and recent research involves the
      development of inhibitors of FVII + tissue factor complex or of FVIIa. This
      approach, if successful, could provide another antithrombotic therapeutics tool.
      The story of FVII well summarizes the efforts of both theoretical and clinical
      approaches in the characterization of a coagulation disorder, that is, among the
      rare bleeding conditions, most frequently encountered in clinical practice. 

PMID- 25973587
TI  - Direct oral anticoagulants in frail older adults: a geriatric perspective.
AB  - Direct oral anticoagulants (DOACs) have changed the paradigm of anticoagulation
      management, improving patient convenience as well as possibly reducing the
      incidence of spontaneous intracranial hemorrhage. However, concerns remain with
      these agents because of the lack of monitoring capacity and availability of
      readily accessible specific antidotes. This is particularly pertinent in the
      older population, specifically the frail older adults who have multiple
      comorbidities, higher risk of falls, and increased bleeding risk. This group has
      not been specifically studied in the DOAC randomized controlled trials and,
      hence, extrapolation of these data into this population should be done
      cautiously. We provide a review of the use of DOACs in the older frail population
      from both hematological and geriatric perspectives, as well as propose an
      algorithm for how these agents may be used in this frail population. 

PMID- 25973588
TI  - Methylation reactions, the redox balance and atherothrombosis: the search for a
      link with hydrogen sulfide.
AB  - It is now clear that homocysteine (Hcy) is irreversibly degraded to hydrogen
      sulfide (H(2)S), an endogenous gasotransmitter that causes in vivo platelet
      activation via upregulation of phospholipase A2 and downstream boost of the
      arachidonate cascade. This mechanism involves a transsulfuration pathway. Based
      on these new data, clinical and experimental models on the relationships between
      Hcy and folate pathways in vascular disease and information on the Hcy
      controversy have been reanalyzed in the present review. Most interventional
      trials focused on Hcy lowering by folate administration did not exclude patients
      routinely taking the arachidonate inhibitor aspirin. This may have influenced the
      results of some of these trials. It is also clear that nutritional intake of
      folate affects several enzymatic reactions of the methionine-Hcy cycle and
      associated one-carbon metabolism and, thereby, both methylation reactions and
      redox balance. Hence, it is conceivable that the abnormally high Hcy levels seen
      in pathologic states reflect a poorly elucidated perturbation of such reactions
      and of such balance. While it is unknown whether there is an interplay between
      H2S, methylation reactions, and redox balance, measuring the sole reduction of
      blood Hcy that follows folate administration may well be an oversimplified
      approach to a complex biologic perturbation. The need to investigate this complex
      framework is thoroughly discussed in this article.

PMID- 25973589
TI  - Coagulase Activity by Staphylococcus aureus: A Potential Target for Therapy?
AB  - Staphylococcus aureus is a leading cause of skin and soft tissue infections,
      foreign body infections, and infective endocarditis. In case of endovascular
      infection with S. aureus, higher rates of cardiac valve destruction, embolic
      complications, severe sepsis, and death occur. The unique capacity of S. aureus
      to induce clotting has been known for over a century; however, its role in
      virulence has long been controversial. S. aureus secretes two coagulases,
      staphylocoagulase and von Willebrand factor binding protein that both activate
      prothrombin to generate fibrin. A better understanding of the molecular
      mechanisms as well as the new strategies to target the coagulases have
      highlighted their importance in S. aureus virulence. Coagulase activity is
      essential for the formation of S. aureus-fibrin-platelet microaggregates and for
      the homing of S. aureus to the vascular wall under flow. Absence or inhibition of
      S. aureus coagulase activity improved outcome in disease models of skin
      infection, sepsis, catheter infection, and endocarditis. Here, we review how the
      manipulation of the host's hemostatic system contributes to the disease-causing
      potential of S. aureus and discuss the S. aureus coagulases as promising targets
      for novel therapeutic strategies. 

PMID- 25973596
TI  - Behavioral response of spotted-wing drosophila, Drosophila suzukii Matsumura, to
      aversive odors and a potential oviposition deterrent in the field.
AB  - BACKGROUND: Drosophilia suzukii Matsumura is an invasive pest insect that lays
      its eggs in the fruit of several commercially grown crops. An effective
      oviposition deterrent could contribute to its management. Repellant odors were
      evaluated in the laboratory and in the field. RESULTS: Geosmin and 1-octen-3-ol
      were found to be aversive to seven-day-old female D. suzukii at concentrations of
      10(-1) and 10(-2) in laboratory choice tests. Field experiments found that fewer
      eggs were observed in fruit on the day of harvest and fewer adult D. suzukii were
      reared from fruit associated with 1-octen-3-ol odors than control fruit in
      cultivated red raspberry. CONCLUSION: Geosmin and 1-octen-3-ol induce aversive
      behaviors in Drosophila suzukii and are potential oviposition deterrents for its
      management in fruit crops.

PMID- 25973597
TI  - Limitations of the definition of sarcopenia in cancer surgery.

PMID- 25973598
TI  - Recent advances in transition metal-catalyzed C-H bond functionalization of
      ferrocene derivatives.
AB  - Transition metal-catalyzed C-H bond functionalizations of ferrocene derivatives
      have emerged in the last few years as a versatile tool in synthetic
      organometallic chemistry. These protocols offer significant advantages over more
      traditional approaches for the synthesis of functionalized ferrocene derivatives
      in terms of both atom- and step-economy. In this Perspective, we aim to showcase
      the state of the art in this field, with special emphasis on recent asymmetric
      methodologies. 

PMID- 25973599
TI  - Clinical Predictors of Pacemaker Implantation in Patients with Syncope Receiving
      Implantable Loop Recorder with or without ECG Conduction Abnormalities.
AB  - BACKGROUND: Implantable loop recorders (ILR) allow prolonged cardiac rhythm
      monitoring and improved diagnostic yield in syncope patients. Predictive factors
      for pacemaker (PM) implantation in the ILR population with unexplained syncope
      have not been adequately investigated. In this single center, retrospective,
      observational study we investigated factors that predict PM implantation in this
      population. METHODS: We retrospectively analyzed our ILR database of patients
      aged over 18 years who underwent ILR implantation for unexplained syncope between
      January 2009 and June 2013. Patient case notes were examined for demographics,
      history, electrocardiogram (ECG) abnormalities, investigations, and events during
      follow-up. The primary end-point was the detection of a symptomatic or
      asymptomatic bradycardia requiring PM implantation. RESULTS: During a period of
      4.5 years, 200 patients were implanted with ILR for unexplained syncope, of who n
      = 33 (16.5%) had clinically significant bradycardia requiring PM implantation.
      After multivariable analysis, history of injury secondary to syncope was found to
      be the strongest independent predictor for PM implantation (odds ratio [OR]:9.1;
      P < 0.001; 95% confidence interval [CI]: (3.26-26.81). Other significant
      predictors included female sex, PR interval > 200msec, and age >75 years. In
      patients without conduction abnormalities on the ECG, history of injury secondary
      to syncope was found to be the strongest independent predictor for PM
      implantation (OR: 8.16; P = 0.00027; 95% [CI]: (2.67-26.27). CONCLUSIONS: A
      history of injury secondary to syncope and female sex were independent predictive
      factors for bradycardia necessitating PM implantation in patients receiving an
      ILR for syncope with or without ECG conduction abnormalities.

PMID- 25973600
TI  - Nonlinear Lock-In Infrared Microscopy: A Complementary Investigation Technique
      for the Analysis of Functional Electroceramic Components.
AB  - Using lock-in infrared microscopy as a tool for current detection on the
      micrometer scale in AC-driven specimens in combination with iterative grinding
      procedure allows preparation of current dominating microstructure regions on well
      polished surfaces. This technique is applied successfully on varistor components
      based on specially doped ZnO-based varistor ceramics. This peculiar
      electroceramic material exhibits exceptional high nonlinear current-voltage (I-V)
      characteristics, described by a power law according I~V(alpha), caused by double
      Schottky barriers at the grain boundaries. As a novelty the thermographic
      response is used to evaluate local electrical properties, namely the nonlinearity
      coefficient alpha, on basis of higher order harmonics with respect to the basic
      electrical driving AC-frequency. To correlate the observed electrical properties
      to the microstructure, the polar crystal orientation of the relevant ZnO grains
      is determined by combining electron backscatter diffraction and orientation
      dependent patterns as a result of a chemical etching procedure. These findings
      support a modified new model for describing the grain boundary controlled current
      flow in a varistor microstructure including orientation-dependent barrier
      properties. Hence, the experimentally observed current direction-dependent
      behavior can be described consistently.

PMID- 25973601
TI  - Autoselection of cytoplasmic yeast virus like elements encoding toxin/antitoxin
      systems involves a nuclear barrier for immunity gene expression.
AB  - Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia
      acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and
      encode toxic anticodon nucleases (ACNases) along with specific immunity proteins.
      Here we show that nuclear, not cytoplasmic expression of either immunity gene
      (PaORF4, KlORF3 or DrORF5) results in transcript fragmentation and is
      insufficient to establish immunity to the cognate ACNase. Since rapid
      amplification of 3' ends (RACE) as well as linker ligation of immunity
      transcripts expressed in the nucleus revealed polyadenylation to occur along with
      fragmentation, ORF-internal poly(A) site cleavage due to the high A/T content is
      likely to prevent functional expression of the immunity genes. Consistently,
      lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis
      entirely prevented transcript cleavage and permitted functional nuclear
      expression leading to full immunity against the respective ACNase toxin.
      Consistent with a specific adaptation of the immunity proteins to the cognate
      ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor
      KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of
      functional nuclear recruitment of VLE encoded genes, in particular those involved
      in autoselection of the VLEs via a toxin/antitoxin principle. 

PMID- 25973603
TI  - Correction: TCTP is an androgen-regulated gene implicated in prostate cancer.

PMID- 25973602
TI  - Enabling the Development and Deployment of Next Generation Point-of-Care
      Diagnostics.

PMID- 25973605
TI  - A generalized simplest equation method and its application to the Boussinesq
      Burgers equation.
AB  - In this paper, a generalized simplest equation method is proposed to seek exact
      solutions of nonlinear evolution equations (NLEEs). In the method, we chose a
      solution expression with a variable coefficient and a variable coefficient
      ordinary differential auxiliary equation. This method can yield a Backlund
      transformation between NLEEs and a related constraint equation. By dealing with
      the constraint equation, we can derive infinite number of exact solutions for
      NLEEs. These solutions include the traveling wave solutions, non-traveling wave
      solutions, multi-soliton solutions, rational solutions, and other types of
      solutions. As applications, we obtained wide classes of exact solutions for the
      Boussinesq-Burgers equation by using the generalized simplest equation method. 

PMID- 25973604
TI  - Cerebellar-dependent associative learning is preserved in Duchenne muscular
      dystrophy: a study using delay eyeblink conditioning.
AB  - OBJECTIVE: Besides progressive muscle weakness cognitive deficits have been
      reported in patients with Duchenne muscular dystrophy (DMD). Cerebellar
      dysfunction has been proposed to explain cognitive deficits at least in part. In
      animal models of DMD disturbed Purkinje cell function has been shown following
      loss of dystrophin. Furthermore there is increasing evidence that the lateral
      cerebellum contributes to cognitive processing. In the present study cerebellar
      dependent delay eyeblink conditioning, a form of associative learning, was used
      to assess cerebellar function in DMD children. METHODS: Delay eyeblink
      conditioning was examined in eight genetically defined male patients with DMD and
      in ten age-matched control subjects. Acquisition, timing and extinction of
      conditioned eyeblink responses (CR) were assessed during a single conditioning
      session. RESULTS: Both groups showed a significant increase of CRs during the
      course of learning (block effect p < 0.001). CR acquisition was not impaired in
      DMD patients (mean total CR incidence 37.4 +/- 17.6%) as compared to control
      subjects (36.2 +/- 17.3%; group effect p = 0.89; group by block effect p = 0.38;
      ANOVA with repeated measures). In addition, CR timing and extinction was not
      different from controls. CONCLUSIONS: Delay eyeblink conditioning was preserved
      in the present DMD patients. Because eyeblink conditioning depends on the
      integrity of the intermediate cerebellum, this older part of the cerebellum may
      be relatively preserved in DMD. The present findings agree with animal model data
      showing that the newer, lateral cerebellum is primarily affected in DMD.

PMID- 25973606
TI  - Lactate dehydrogenase B is associated with the response to neoadjuvant
      chemotherapy in oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) comprises a subset of head and neck squamous
      cell carcinoma (HNSCC) with poor therapeutic outcomes and high glycolytic
      dependency. Neoadjuvant chemotherapy regimens of docetaxel, cisplatin and 5
      fluorouracil (TPF) are currently accepted as standard regimens for HNSCC patients
      with a high risk of distant metastatic spread. However, the antitumor outcomes of
      TPF neoadjuvant chemotherapy in HNSCC remain controversial. This study
      investigated the role of lactate dehydrogenase B (LDHB), a key glycolytic enzyme
      catalyzing the inter-conversion between pyruvate and lactate, in determining
      chemotherapy response and prognosis in OSCC patients. We discovered that a high
      protein level of LDHB in OSCC patients was associated with a poor response to TPF
      regimen chemotherapy as well as poor overall survival and disease-free survival.
      Our in-depth study revealed that high LDHB expression conferred resistance to
      taxol but not 5-fluorouracil or cisplatin. LDHB deletion sensitized OSCC cell
      lines to taxol, whereas the introduction of LDHB decreased sensitivity to taxol
      treatment. Taxol induced a pronounced impact on LDHB-down-regulated OSCC cells in
      terms of apoptosis, G2/M phase cell cycle arrest and energy metabolism. In
      conclusion, our study highlighted the critical role of LDHB in OSCC and proposed
      that LDHB could be used as a biomarker for the stratification of patients for TPF
      neoadjuvant chemotherapy and the determination of prognosis in OSCC patients. 

PMID- 25973607
TI  - When correction turns positive: processing corrective prosody in Dutch.
AB  - Current research on spoken language does not provide a consistent picture as to
      whether prosody, the melody and rhythm of speech, conveys a specific meaning.
      Perception studies show that English listeners assign meaning to prosodic
      patterns, and, for instance, associate some accents with contrast, whereas Dutch
      listeners behave more controversially. In two ERP studies we tested how Dutch
      listeners process words carrying two types of accents, which either provided new
      information (new information accents) or corrected information (corrective
      accents), both in single sentences (experiment 1) and after corrective and new
      information questions (experiment 2). In both experiments corrective accents
      elicited a sustained positivity as compared to new information accents, which
      started earlier in context than in single sentences. The positivity was not
      modulated by the nature of the preceding question, suggesting that the underlying
      neural mechanism likely reflects the construction of an interpretation to the
      accented word, either by identifying an alternative in context or by inferring it
      when no context is present. Our experimental results provide strong evidence for
      inferential processes related to prosodic contours in Dutch. 

PMID- 25973609
TI  - Isotopic niche variation in a higher trophic level ectotherm: highlighting the
      role of succulent plants in desert food webs.
AB  - Stable isotope analysis of animal tissues allows description of isotopic niches,
      whose axes in an n-dimensional space are the isotopic ratios, compared to a
      standard, of different isotope systems (e.g. delta(13)C, delta(15)N). Isotopic
      niches are informative about where an animal, population or species lives and
      about what it consumes. Here we describe inter- and intrapopulation isotopic
      niche (bidimensional delta(13)C-delta(15)N space) of the Orange-throated whiptail
      (Aspidoscelis hyperythra), an arthropodivorous small lizard, in ten localities of
      Baja California Sur (Mexico). These localities range from extreme arid to
      subtropical conditions. Between 13 and 20 individuals were sampled at each
      locality and 1 cm of tail-tip was collected for isotope analysis. As expected,
      interpopulation niche width variation was much larger than intrapopulation one.
      Besides, isotopic variation was not related to age, sex or individual size of
      lizards. This suggests geographic variation of the isotopic niche was related to
      changes in the basal resources that fuel the trophic web at each locality. The
      position of Bayesian isotope ellipses in the delta-space indicated that whiptails
      in more arid localities were enriched in 13C, suggesting most of the carbon they
      ingested came from CAM succulent plants (cacti, agaves) and in minor degree in C4
      grasses. Contrarily, whiptails in subtropical areas were depleted in 13C, as they
      received more carbon from C3 scrubs and trees. Localities closer to sea-level
      tended to be enriched in 15N, but a clear influence of marine subsidies was
      detected only at individual level. The study contributes to identify the origin
      and pathways through which energy flows across the trophic webs of North American
      deserts.

PMID- 25973610
TI  - The physico-chemical properties of dietary fibre determine metabolic responses,
      short-chain Fatty Acid profiles and gut microbiota composition in rats fed low-
      and high-fat diets.
AB  - The aim of this study was to investigate how physico-chemical properties of two
      dietary fibres, guar gum and pectin, affected weight gain, adiposity, lipid
      metabolism, short-chain fatty acid (SCFA) profiles and the gut microbiota in male
      Wistar rats fed either low- or high-fat diets for three weeks. Both pectin and
      guar gum reduced weight gain, adiposity, liver fat and blood glucose levels in
      rats fed a high-fat diet. Methoxylation degree of pectin (low, LM and high (HM))
      and viscosity of guar gum (low, medium or high) resulted in different effects in
      the rats, where total blood and caecal amounts of SCFA were increased with guar
      gum (all viscosities) and with high methoxylated (HM) pectin. However, only guar
      gum with medium and high viscosity increased the levels of butyric acid in caecum
      and blood. Both pectin and guar gum reduced cholesterol, liver steatosis and
      blood glucose levels, but to varying extent depending on the degree of
      methoxylation and viscosity of the fibres. The medium viscosity guar gum was the
      most effective preparation for prevention of diet-induced hyperlipidaemia and
      liver steatosis. Caecal abundance of Akkermansia was increased with high-fat
      feeding and with HM pectin and guar gum of all viscosities tested. Moreover, guar
      gum had distinct bifidogenic effects independent of viscosity, increasing the
      caecal abundance of Bifidobacterium ten-fold. In conclusion, by tailoring the
      viscosity and possibly also the degree of methoxylation of dietary fibre,
      metabolic effects may be optimized, through a targeted modulation of the gut
      microbiota and its metabolites. 

PMID- 25973608
TI  - Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through
      Multiple Mechanisms.
AB  - Varicella zoster virus (VZV) causes chickenpox in humans and, subsequently,
      establishes latency in the sensory ganglia from where it reactivates to cause
      herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV)
      recapitulates VZV pathogenesis in humans thus representing a suitable animal
      model for VZV infection. While the type I interferon (IFN) response has been
      shown to affect VZV replication, the virus employs counter mechanisms to prevent
      the induction of anti-viral IFN stimulated genes (ISG). Here, we demonstrate that
      SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway.
      SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying
      reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous
      work implicated involvement of the VZV immediate early gene product ORF63 in
      preventing ISG-induction we studied the role of SVV ORF63 in generating
      resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2
      phosphorylation but caused IRF9 degradation in a proteasome-dependent manner,
      suggesting that SVV employs multiple mechanisms to counteract the effect of IFN.
      Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase
      (DHFR)-degradation domain additionally confirmed its requirement for viral
      replication. Our results also show a prominent reduction of IRF9 and inhibition
      of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV
      ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein.
      Taken together, our data suggest that varicella ORF63 prevents ISG-induction both
      directly via IRF9 degradation and indirectly via transcriptional control of viral
      proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode
      multiple viral gene products that tightly control IFN-induced anti-viral
      responses. 

PMID- 25973611
TI  - Nuclear species-diagnostic SNP markers mined from 454 amplicon sequencing reveal
      admixture genomic structure of modern citrus varieties.
AB  - Most cultivated Citrus species originated from interspecific hybridisation
      between four ancestral taxa (C. reticulata, C. maxima, C. medica, and C.
      micrantha) with limited further interspecific recombination due to vegetative
      propagation. This evolution resulted in admixture genomes with frequent
      interspecific heterozygosity. Moreover, a major part of the phenotypic diversity
      of edible citrus results from the initial differentiation between these taxa.
      Deciphering the phylogenomic structure of citrus germplasm is therefore essential
      for an efficient utilization of citrus biodiversity in breeding schemes. The
      objective of this work was to develop a set of species-diagnostic single
      nucleotide polymorphism (SNP) markers for the four Citrus ancestral taxa covering
      the nine chromosomes, and to use these markers to infer the phylogenomic
      structure of secondary species and modern cultivars. Species-diagnostic SNPs were
      mined from 454 amplicon sequencing of 57 gene fragments from 26 genotypes of the
      four basic taxa. Of the 1,053 SNPs mined from 28,507 kb sequence, 273 were found
      to be highly diagnostic for a single basic taxon. Species-diagnostic SNP markers
      (105) were used to analyse the admixture structure of varieties and rootstocks.
      This revealed C. maxima introgressions in most of the old and in all recent
      selections of mandarins, and suggested that C. reticulata * C. maxima
      reticulation and introgression processes were important in edible mandarin
      domestication. The large range of phylogenomic constitutions between C.
      reticulata and C. maxima revealed in mandarins, tangelos, tangors, sweet oranges,
      sour oranges, grapefruits, and orangelos is favourable for genetic association
      studies based on phylogenomic structures of the germplasm. Inferred admixture
      structures were in agreement with previous hypotheses regarding the origin of
      several secondary species and also revealed the probable origin of several acid
      citrus varieties. The developed species-diagnostic SNP marker set will be useful
      for systematic estimation of admixture structure of citrus germplasm and for
      diverse genetic studies. 

PMID- 25973612
TI  - Transcriptional Profiling of Host Gene Expression in Chicken Embryo Fibroblasts
      Infected with Reticuloendotheliosis Virus Strain HA1101.
AB  - Reticuloendotheliosis virus (REV), a member of the Gammaretrovirus genus in the
      Retroviridae family, causes an immunosuppressive, oncogenic and runting-stunting
      syndrome in multiple avian hosts. To better understand the host interactions at
      the transcriptional level, microarray data analysis was performed in chicken
      embryo fibroblast cells at 1, 3, 5, and 7 days after infection with REV. This
      study identified 1,785 differentially expressed genes that were classified into
      several functional groups including signal transduction, immune response,
      biological adhesion and endocytosis. Significant differences were mainly observed
      in the expression of genes involved in the immune response, especially during the
      later post-infection time points. These results revealed that differentially
      expressed genes IL6, STAT1, MyD88, TLRs, NF-kappaB, IRF-7, and ISGs play
      important roles in the pathogenicity of REV infection. Our study is the first to
      use microarray analysis to investigate REV, and these findings provide insights
      into the underlying mechanisms of the host antiviral response and the molecular
      basis of viral pathogenesis. 

PMID- 25973613
TI  - Engineering D-Amino Acid Containing Collagen Like Peptide at the Cleavage Site of
      Clostridium histolyticum Collagenase for Its Inhibition.
AB  - Collagenase is an important enzyme which plays an important role in degradation
      of collagen in wound healing, cancer metastasis and even in embryonic
      development. However, the mechanism of this degradation has not yet been
      completely understood. In the field of biomedical and protein engineering, the
      design and development of new peptide based materials is of main concern. In the
      present work an attempt has been made to study the effect of DAla in collagen
      like peptide (imino-poor region of type I collagen) on the structure and
      stability of peptide against enzyme hydrolysis. Effect of replacement of DAla in
      the collagen like peptide has been studied using circular dichroic spectroscopy
      (CD). Our findings suggest that, DAla substitution leads to conformational
      changes in the secondary structure and favours the formation of polyproline II
      conformation than its L-counterpart in the imino-poor region of collagen like
      peptides. Change in the chirality of alanine at the cleavage site of collagenase
      in the imino-poor region inhibits collagenolytic activity. This may find
      application in design of peptides and peptidomimics for enzyme-substrate
      interaction, specifically with reference to collagen and other extra cellular
      matrix proteins. 

PMID- 25973615
TI  - Impact of crisis resource management simulation-based training for
      interprofessional and interdisciplinary teams: A systematic review.
AB  - Crisis resource management (CRM) abilities are important for different healthcare
      providers to effectively manage critical clinical events. This study aims to
      review the effectiveness of simulation-based CRM training for interprofessional
      and interdisciplinary teams compared to other instructional methods (e.g.,
      didactics). Interprofessional teams are composed of several professions (e.g.,
      nurse, physician, midwife) while interdisciplinary teams are composed of several
      disciplines from the same profession (e.g., cardiologist, anaesthesiologist,
      orthopaedist). Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled
      Trials, and ERIC were searched using terms related to CRM, crisis management,
      crew resource management, teamwork, and simulation. Trials comparing simulation
      based CRM team training versus any other methods of education were included. The
      educational interventions involved interprofessional or interdisciplinary
      healthcare teams. The initial search identified 7456 publications; 12 studies
      were included. Simulation-based CRM team training was associated with significant
      improvements in CRM skill acquisition in all but two studies when compared to
      didactic case-based CRM training or simulation without CRM training. Of the 12
      included studies, one showed significant improvements in team behaviours in the
      workplace, while two studies demonstrated sustained reductions in adverse patient
      outcomes after a single simulation-based CRM team intervention. In conclusion,
      CRM simulation-based training for interprofessional and interdisciplinary teams
      show promise in teaching CRM in the simulator when compared to didactic case
      based CRM education or simulation without CRM teaching. More research, however,
      is required to demonstrate transfer of learning to workplaces and potential
      impact on patient outcomes. 

PMID- 25973614
TI  - Combining Active Immunization with Monoclonal Antibody Therapy To Facilitate
      Early Initiation of a Long-Acting Anti-Methamphetamine Antibody Response.
AB  - We hypothesized that an anti-METH mAb could be used in combination with a METH
      conjugate vaccine (MCV) to safely improve the overall quality and magnitude of
      the anti-METH immune response. The benefits would include immediate onset of
      action (from the mAb), timely increases in the immune responses (from the
      combined therapy) and duration of antibody response that could last for months
      (from the MCV). A novel METH-like hapten (METH-SSOO9) was synthesized and then
      conjugated to immunocyanin monomers of keyhole limpet hemocyanin (IC(KLH)) to
      create the MCV ICKLH-SOO9. The vaccine, in combination with previously discovered
      anti-METH mAb7F9, was then tested in rats for safety and potential efficacy. The
      combination antibody therapy allowed safe achievement of an early high anti-METH
      antibody response, which persisted throughout the study. Indeed, even after 4
      months the METH vaccine antibodies still had the capacity to significantly reduce
      METH brain concentrations resulting from a 0.56 mg/kg METH dose.

PMID- 25973616
TI  - Comparative analysis of genetic variation in kava (Piper methysticum) assessed by
      SSR and DArT reveals zygotic foundation and clonal diversification.
AB  - Kava (Piper methysticum) is a major cash crop in the Pacific. The aim of this
      study was to assess genetic variation among 103 accessions of kava using SSRs and
      DArTs. Genetic structure was determined using clustering analyses (WPGMA) and
      principal coordinate analyses (PCA). Thirteen SSR primers and 75 DArT markers
      were found polymorphic, and the two types of markers generated similar clustering
      patterns. Genetic distances ranged from 0 to 0.65 with an average of 0.24 using
      SSRs and from 0 to 0.64 with an average of 0.24 using DArT. Eleven genotypes were
      identified with SSR while 28 genotypes were identified with DArT markers. By
      combining the two sets of markers, a total of only 30 distinct genotypes were
      observed. In the Vanuatu archipelago, noble cultivars originating from different
      islands clustered together within a very narrow genetic base despite their
      diversity of morphotypes. SSR and DArT fingerprints allowed the identification of
      kava cultivars unsuitable for consumption, so called two-days, and clearly
      differentiated the wild types classified as P. methysticum var. wichmannii from
      the cultivars as var. methysticum. Molecular data reveals that all noble
      cultivars evolved by the predominance of clonal selection. Although they are
      represented by clearly distinct morphotypes, these cultivars are genetically
      vulnerable and their potential to adapt to forthcoming changes is limited. These
      newly developed markers provide high resolution and will be useful for kava
      diversity analyses and quality assessment. 

PMID- 25973617
TI  - Hematologic and Biochemical Reference Values of the Australian Bush Rat (Rattus
      fuscipes).
AB  - We provide hematologic (n = 34) and biochemical (n = 30) blood values for wild
      caught Australian bush rats (Rattus fuscipes). Hematology values have similar
      range limits compared with other rat species. Biochemistry values for glucose,
      alanine transaminase, aspartate aminotransferase, and creatine kinase have higher
      maximum ranges compared with other rats.

PMID- 25973618
TI  - CHARACTERIZATION OF PORCINE PARVOVIRUS TYPE 3 AND PORCINE CIRCOVIRUS TYPE 2 IN
      WILD BOARS (SUS SCROFA) IN SLOVAKIA.
AB  - As the number of free-living wild boars (Sus scrofa L.) continues to rise in
      Slovakia, the probability of pathogen transmission between susceptible species
      increases. We investigated the distribution and genetic characterization of
      porcine parvovirus type 3 (PPV3), porcine circovirus type 2 (PCV2), and their
      coinfection in wild boars. Among 194 animals tested, 19.1% were positive for PPV3
      and 43.8% for PCV2. Similar rates of coinfection with both viruses reaching 11.0%
      and 11.8% were observed in juvenile and mature wild boars, respectively.
      Phylogenetic analysis of PPV3 sequences from VP1 and NS1 genomic regions revealed
      a close genetic relationship among isolates from Slovakia and those sampled
      worldwide. Prevalence of PCV2 in wild boars was lower than that reported in
      domestic pigs in Slovakia. The PCV2 variants originating from sylvatic and
      domestic hosts in Slovakia were grouped in the same clusters, namely PCV2b-1A/1B
      and PCV2a-2D. 

PMID- 25973619
TI  - BAYESIAN ANALYSIS TO EVALUATE TESTS FOR THE DETECTION OF MYCOBACTERIUM BOVIS
      INFECTION IN FREE-RANGING WILD BISON (BISON BISON ATHABASCAE) IN THE ABSENCE OF A
      GOLD STANDARD.
AB  - We estimated the sensitivity and specificity of the caudal-fold skin test (CFT),
      the fluorescent polarization assay (FPA), and the rapid lateral-flow test (RT)
      for the detection of Mycobacterium bovis in free-ranging wild wood bison (Bison
      bison athabascae), in the absence of a gold standard, by using Bayesian analysis,
      and then used those estimates to forecast the performance of a pairwise
      combination of tests in parallel. In 1998-99, 212 wood bison from Wood Buffalo
      National Park (Canada) were tested for M. bovis infection using CFT and two
      serologic tests (FPA and RT). The sensitivity and specificity of each test were
      estimated using a three-test, one-population, Bayesian model allowing for
      conditional dependence between FPA and RT. The sensitivity and specificity of the
      combination of CFT and each serologic test in parallel were calculated assuming
      conditional independence. The test performance estimates were influenced by the
      prior values chosen. However, the rank of tests and combinations of tests based
      on those estimates remained constant. The CFT was the most sensitive test and the
      FPA was the least sensitive, whereas RT was the most specific test and CFT was
      the least specific. In conclusion, given the fact that gold standards for the
      detection of M. bovis are imperfect and difficult to obtain in the field,
      Bayesian analysis holds promise as a tool to rank tests and combinations of tests
      based on their performance. Combining a skin test with an animal-side serologic
      test, such as RT, increases sensitivity in the detection of M. bovis and is a
      good approach to enhance disease eradication or control in wild bison. 

PMID- 25973621
TI  - EVALUATION OF ANTHELMINTIC FISHMEAL POLYMER BAITS FOR THE CONTROL OF
      BAYLISASCARIS PROCYONIS IN FREE-RANGING RACCOONS (PROCYON LOTOR).
AB  - Baylisascaris procyonis is a common gastrointestinal parasite of raccoons
      (Procyon lotor) and is a zoonotic helminth with the potential to cause severe or
      fatal infection. Raccoons thrive in human-dominated landscapes, and the fecal
      oral transmission pathway and lack of effective treatment make B. procyonis a
      serious threat to public health. The distribution of medicinal baits has emerged
      as a socially acceptable and cost-effective method for managing disease in free
      ranging wildlife. We assessed the suitability of a mass-producible anthelmintic
      bait for B. procyonis mitigation by evaluating the willingness of free-ranging
      raccoons to consume anthelmintic baits and determining whether bait consumption
      successfully cleared B. procyonis infections from raccoons. Anthelmintic baits
      were modified from standard fishmeal polymer baits, the food attractant commonly
      used in oral rabies vaccine baits, with the introduction of 220 mg of pyrantel
      pamoate into the fishmeal mixture. We captured 16 naturally infected raccoons,
      presented one anthelmintic bait, and monitored B. procyonis infection over 90 d
      by screening feces for eggs. Treatment cleared B. procyonis infections for nine
      of 12 raccoons that consumed >10 g of the 15 g bait. We used remote cameras to
      monitor in situ patterns of bait consumption for anthelmintic baits relative to
      standard baits. Both anthelmintic and standard baits were rapidly consumed, with
      no differences in the rate of consumption between bait types. However, after bait
      contact, raccoons demonstrated a greater willingness to consume standard baits
      while ignoring anthelmintic baits more frequently (P = 0.06). Initial trials of
      anthelmintic baits show promise, although refinement in both dose and
      palatability is needed. At mass production scales, the addition of pyrantel
      pamoate to fishmeal polymer baits would be inexpensive, potentially making
      anthelmintic baits a viable management option when coupled with an oral rabies
      vaccine or used independently for B. procyonis mitigation.

PMID- 25973622
TI  - CLIMATE AND HABITAT INFLUENCE PREVALENCE OF MENINGEAL WORM INFECTION IN NORTH
      DAKOTA, USA.
AB  - The meningeal worm (Parelaphostrongylus tenuis) is a parasite of white-tailed
      deer (Odocoileus virginianus) and is also a significant pathogen of moose (Alces
      alces) and other ungulates. Changes in climate or habitat may facilitate range
      expansion or increase the prevalence of meningeal worm infection in white-tailed
      deer, resulting in increased exposure to susceptible ungulates. We examined 3,730
      white-tailed deer during 2002-05 to determine the prevalence and range of
      meningeal worm infection in North Dakota, US, and investigated whether these had
      changed since earlier surveys. We used multiple logistic regression to model
      potential effects of habitat and climate on prevalence in white-tailed deer. We
      also examined how habitat influences intermediate hosts by comparing gastropod
      abundance and microclimate among habitat types. Prevalence in deer was 14%
      statewide, and prevalence and geographic range had increased since the early 1990
      s. Natural woodlands provided the best habitat for intermediate hosts, and
      increases in prevalence of infection in deer may be due to recent patterns in
      growing-season precipitation. This study has redefined the geographic
      distribution of meningeal worm infection and increased understanding of how
      climate and habitat influence the prevalence and distribution of this parasite.

PMID- 25973623
TI  - Survey for Trichomonas gallinae in Northern Bobwhites (Colinus virginianus) from
      the Rolling Plains Ecoregion, Oklahoma and Texas, USA.
AB  - Northern Bobwhites (Colinus virginianus) have been in decline throughout the
      southeastern US. Prevalence of Trichomonas gallinae in wild bobwhites is unknown,
      although T. gallinae caused morbidity and mortality in experimentally infected
      bobwhites. Many species of Columbidae (pigeons and doves) in Texas are hosts to
      T. gallinae. Bobwhites potentially may become exposed to this protozoan through
      supplemental feed or water sources contaminated by columbids infected with T.
      gallinae. All of 506 bobwhites collected in Oklahoma and Texas, 2011-13, were PCR
      negative for T. gallinae. These data suggest T. gallinae is not contributing to
      the population decline of bobwhites in this region. 

PMID- 25973624
TI  - TUBERCULOSIS AND BRUCELLOSIS IN WOOD BISON (BISON BISON ATHABASCAE) IN NORTHERN
      CANADA: A RENEWED NEED TO DEVELOP OPTIONS FOR FUTURE MANAGEMENT.
AB  - Effective, long-term strategies to manage the threat of bovine tuberculosis and
      brucellosis spillback from northern, diseased bison to the Canadian cattle herd
      and adjacent disease-free wood bison (Bison bison athabascae) herds have eluded
      policy makers in recent decades. A controversial plan to depopulate infected
      herds and repopulate them with disease-free wood bison was rejected in 1990
      because of significant public concern. Since then, technical advances in vaccine
      technology, genetic salvage, selective culling, and diagnostic test development
      have occurred. Containment strategies to reduce further spread of these diseases
      are a necessary first step; recent progress has been made in this area, but
      challenges remain. This progress has produced more options for management of
      these herds in northern Canada, and it is time to consider wood bison
      conservation and long-term disease eradication as equally important goals that
      must satisfy concerns of conservation groups, agriculture sectors, aboriginal
      groups, and the general public. Management of wildlife disease reservoirs in
      other areas, including Yellowstone and Riding Mountain national parks, has
      demonstrated that effective disease management is possible. Although combinations
      of different strategies, including vaccination, genetic salvage techniques, and
      selective culling, that use sensitive and specific diagnostic tests may offer
      alternatives to depopulation/repopulation, they also have logistic constraints
      and cost implications that will need consideration in a multistakeholder,
      collaborative-management framework. We feel the time is right for this
      discussion, so a long-term solution to this problem can be applied. 

PMID- 25973625
TI  - PREVALENCE OF SULFONAMIDE AND FLORFENICOL RESISTANCE GENES IN ESCHERICHIA COLI
      ISOLATED FROM YAKS (BOS GRUNNIENS) AND HERDSMEN IN THE TIBETAN PASTURE.
AB  - To determine the antimicrobial susceptibility profiles and prevalence of
      resistance genes in Escherichia coli isolated from yaks (Bos grunniens) and
      herdsmen in nine plateau pastures in Tibet, we isolated 184 nonidentical strains
      of E. coli from yaks and herdsmen. Antimicrobial susceptibility testing of 15
      antimicrobials was conducted and the prevalence of sulfonamide resistance genes
      (sul1, sul2, and sul3) and florfenicol resistance genes (floR, cfr, cmlA, fexA,
      pexA, and estDL136) was determined. Escherichia coli isolated from yaks had a
      high resistance rate to sulfamethoxazole (44%), sulphafurazole (40.4%), and
      florfenicol (11.4%). Escherichia coli isolated from herdsmen had a high
      resistance rate to sulfamethoxazole (57%) and sulphafurazole (51%). In addition,
      sul genes were present in 93% of sulfonamide-resistant isolates (84/90), and 17
      floR genes and four cmlA genes were found in 19 florfenicol-resistant isolates.
      Even though florfenicol is prohibited from use in humans, three floR genes were
      detected in strains isolated from herdsmen. The three floR-positive isolates from
      herdsmen had pulsed-field gel electrophoresis patterns similar to isolates from
      yaks. In addition to documenting the sul and floR genes in E. coli isolated from
      yaks and herdsmen in the Tibetan pasture, we demonstrated the potential risk that
      antimicrobial-resistant E. coli could spread among herdsmen and yaks. 

PMID- 25973626
TI  - KNEMIDOKOPTINID (EPIDERMOPTIDAE: KNEMIDOKOPTINAE) MITE INFESTATION IN WILD RED
      CROWNED PARAKEETS (CYANORAMPHUS NOVAEZELANDIAE): CORRELATIONS BETWEEN MACROSCOPIC
      AND MICROSCOPIC FINDINGS.
AB  - During a study on health and disease in Red-crowned Parakeets (Cyanoramphus
      novaezelandiae) on Tiritiri Matangi Island and Little Barrier Island (Hauturu-o
      Toi) in New Zealand between 2011 and 2013, an outbreak of feather loss prompted
      the collection of skin biopsies (n = 135) under anesthesia from the head of
      captured birds. A subset of samples (n = 7) was frozen to obtain whole specimens
      for identification of ectoparasites. Mites (range 1-11) were observed in 79/135
      (58.5%) skin biopsies, whereas feather loss was only found in 47/142 (33.1%)
      birds captured during the sampling period. Compact orthokeratotic hyperkeratosis
      and acanthosis were found in association with mites. Procnemidocoptes janssensi
      (Acari: Epidermoptidae, Knemidokoptinae) was identified from whole mites obtained
      from skin biopsies. We describe the presence, pathology, and stages of
      infestation for knemidokoptinid mange in a wild parrot population in New Zealand.
      Given the clinical and pathologic changes observed and poor knowledge of the
      parasite's New Zealand host and geographic distribution, further work is
      recommended for this and sympatric parrots, to understand relationships between
      the host, parasite, environment, and expression of disease. Results from this
      study reinforce the value of including biopsy samples for the investigation of
      skin disease in wild birds, particularly to link etiologic agents with pathologic
      changes.

PMID- 25973627
TI  - Multidrug-resistant Salmonella enterica Serovar Typhimurium Monophasic Variant
      4,12:i:- Isolated from Asymptomatic Wildlife in a Catalonian Wildlife
      Rehabilitation Center, Spain.
AB  - Wildlife can act as long-term asymptomatic reservoirs for zoonotic bacteria, such
      as Salmonella. The prevalence and antimicrobial-susceptibility profiles of
      Salmonella spp. were assessed in 263 cases in wildlife from 22 animal orders from
      a wildlife rehabilitation center in Catalonia (NE Spain), September 2013-May
      2014. Eleven of 263 tested animals were positive for Salmonella spp.,
      representing an overall prevalence of 4.2%. Prevalences by taxonomic categories
      were 2% in mammals, 4.7% in birds, and 4.5% in reptiles. By species, one each of
      European hedgehog (Erinaceus europeus; from a sample of n = 26), Eurasian Eagle
      Owl (Bubo bubo; n = 2), Barn Owl (Tyto alba; n = 3), Tawny Owl (Strix aluco; n =
      20), Egyptian Vulture (Neophron percnopterus; n = 1), Griffon Vulture (Gyps
      fulvus; n = 1), and Hoopoe (Upupa epops; n = 2), and two each Common Kestrels
      (Falco tinnunculus; n = 16) and pond sliders (Trachemys scripta; n = 25) were
      positive for Salmonella. By serotyping, seven of eleven isolates were classified
      as S. enterica subsp. enterica serovar Typhimurium, and five of seven belonged to
      the monophasic variant 4,12:i:-. All the monophasic variants were isolated from
      birds (4/5 in raptors) and showed a multidrug-resistance (MDR) profile to at
      least ampicillin, streptomycin, sulfonamide, and tetracycline (R-type ASSuT), and
      up to 12 antibiotics. The large proportion of S. Typhimurium monophasic MDR
      strains detected in wildlife never treated with antibiotics, especially in
      raptors, adds more complexity to the epidemiologic control of one of the most
      frequent serovars involved in human and livestock infection.

PMID- 25973628
TI  - Spread of the Rat Lungworm (Angiostrongylus cantonensis) in Giant African Land
      Snails (Lissachatina fulica) in Florida, USA.
AB  - The rat lungworm (Angiostrongylus cantonensis) is a parasitic nematode that
      causes rat lungworm disease. It is the leading cause of eosinophilic meningitis
      and is a zoonotic health risk. We confirmed the presence of A. cantonensis using
      species-specific, quantitative PCR in 18 of 50 (36%) giant African land snails
      (Lissachatina fulica) collected from Miami, Florida, US in May 2013. These snails
      were collected from seven of 21 core areas that the Florida Department of
      Agriculture and Consumer Services monitor weekly. Rat lungworms have not
      previously been identified in these areas. Duplicate DNA extractions of foot
      muscle tissue from each snail were tested. Of the seven core areas we examined,
      six were positive for A. cantonensis and prevalence of infection ranged from 27%
      to 100%. Of the 18 positive snails, only five were positive in both extractions.
      Our results confirm an increase in the range and prevalence of rat lungworm
      infection in Miami. We also emphasize the importance of extracting sufficient
      host tissue to minimize false negatives. 

PMID- 25973629
TI  - HERPESVIRUS-ASSOCIATED GENITAL LESIONS IN A STRANDED STRIPED DOLPHIN (STENELLA
      COERULEOALBA) IN THE CANARY ISLANDS, SPAIN.
AB  - An adult male striped dolphin (Stenella coeruleoalba) stranded alive at Arico,
      Tenerife, Canary Islands, Spain. The dolphin died shortly after stranding, and a
      complete postmortem examination was performed. The most remarkable gross findings
      were two fleshy masses of approximately 1 cm diameter, near the tip of the penis.
      These masses were composed of hyperplastic epithelial cells with pigmentary
      incontinence. Ballooning degeneration and margination of chromatin was observed
      within the stratum corneum of the epidermis. A universal nested PCR assay that
      amplifies a conserved region within the polymerase gene of Herpesviridae was
      positive. The sequenced product was most closely related to a gammaherpesvirus
      that shared nucleotide identities of 93% with penile lesions from Atlantic and
      Mediterranean bottlenose dolphins (Tursiops truncatus). This similarity supports
      the hypothesis of sexual transmission between species. 

PMID- 25973630
TI  - Avian Bornaviruses in North American Gulls.
AB  - Avian bornaviruses, recently described members of the family Bornaviridae, have
      been isolated from captive parrots and passerines as well as wild waterfowl in
      which they may cause lethal neurologic disease. We report detection of avian
      bornavirus RNA in the brains of apparently healthy gulls. We tested 439 gull
      brain samples from 18 states, primarily in the northeastern US, using a reverse
      transcriptase PCR assay with primers designed to detect a conserved region of the
      bornavirus M gene. Nine birds yielded a PCR product of appropriate size.
      Sequencing of PCR products indicated that the virus was closely related to
      aquatic bird bornavirus 1 (ABBV-1). Viral RNA was detected in Herring Gulls
      (Larus argentatus), Ring-billed Gulls (Larus delawarensis), and Laughing Gulls
      (Leucophaeus atricilla). Eight of the nine positive birds came from the New
      York/New Jersey area. One positive Herring Gull came from New Hampshire.
      Histopathologic examination of one well-preserved brain from a Herring Gull from
      Union County New Jersey, showed a lymphocytic encephalitis similar to that
      observed in bornavirus-infected parrots and geese. Bornavirus N protein was
      confirmed in two Herring Gull brains by immunohistochemistry. Thus ABBV-1 can
      infect gulls and cause encephalitic brain lesions similar to those observed in
      other birds. 

PMID- 25973631
TI  - Evaluation of Trapper-Collected Nobuto Filter-Paper Blood Samples for Distemper
      and Parvovirus Antibody Detection in Coyotes (Canis latrans) and Raccoons
      (Procyon lotor).
AB  - Blood samples are often collected from free-ranging wildlife for antibody
      detection. However, filter-paper (FP) strips are more cost efficient and easy to
      collect and store. We evaluated trapper-collected FP strips and body-cavity blood
      for canine distemper (CDV) and parvovirus (CPV-2) antibody detection in raccoons
      (Procyon lotor) and coyotes (Canis latrans). From 2008 to 2010, licensed trappers
      near Madison and Milwaukee, Wisconsin, US collected paired samples from harvested
      animals. Canine distemper antibodies were detected using virus neutralization and
      parvovirus antibodies were detected using hemagglutination inhibition. Titers >=
      1:32 for CDV and >= 1:25 for CPV-2 were considered evidence of exposure. Using
      Cohen's kappa test of agreement, FP strip titers agreed with sera for CDV in
      coyotes (n = 28, K = 0.772) and raccoons (n = 29, K = 0.858) and for CPV-2 in
      coyotes (n = 40, K = 0.775) and raccoons (n = 70, K = 0.646). However, raccoons
      determined to be exposed to CPV-2 from sera were unexposed by FP strips in 35% of
      the samples. Titer results may be affected by quality and volume of blood
      samples, interval between collection and processing, small sample sizes, and
      diagnostic testing procedures. Filter-paper strips can be useful for detecting
      CDV and CPV-2 exposure in coyotes and raccoons with correct field sample
      collection and appropriate diagnostic testing procedures.

PMID- 25973632
TI  - Milk sharing in practice: a descriptive analysis of peer breastmilk sharing.
AB  - Peer breastmilk sharing has emerged in recent years as a subject of investigation
      and occasional controversy. Although researchers know that thousands of milk
      exchanges are facilitated through milk sharing Web sites every week, there is
      only limited research into milk sharing practices on the ground. This study
      examines these practices through a 102-item online survey that asked questions
      about milk sharing practices, perceptions of milk sharing, and demographic
      characteristics. Participants were recruited through social media sites specific
      to breastfeeding and parenting events in Central Florida. The sample consisted of
      392 respondents. Data were analyzed using univariate analysis. We found that
      breastmilk sharing is a complex practice, showing high levels of overlap in which
      some donors are also recipients, and that cross-nursing sometimes occurs
      simultaneously with the exchange of expressed milk. Respondents often donated and
      received milk from people they knew; however, exchanging milk with strangers was
      also common. Many but not all used the Internet to facilitate milk exchange;
      participants used well-known milk sharing Web sites as well as their private
      virtual networks. The study found that most milk exchanges happen in-person as
      gifts and that selling and shipping breastmilk were rare. We suggest that further
      research is needed on breastmilk sharing practices to inform breastmilk safety
      research and policy recommendations. 

PMID- 25973633
TI  - Coalescent Histories for Lodgepole Species Trees.
AB  - Coalescent histories are combinatorial structures that describe for a given gene
      tree and species tree the possible lists of branches of the species tree on which
      the gene tree coalescences take place. Properties of the number of coalescent
      histories for gene trees and species trees affect a variety of probabilistic
      calculations in mathematical phylogenetics. Exact and asymptotic evaluations of
      the number of coalescent histories, however, are known only in a limited number
      of cases. Here we introduce a particular family of species trees, the lodgepole
      species trees (lambdan)n >= 0, in which tree lambdan has m = 2n+1 taxa. We
      determine the number of coalescent histories for the lodgepole species trees, in
      the case that the gene tree matches the species tree, showing that this number
      grows with m!! in the number of taxa m. This computation demonstrates the
      existence of tree families in which the growth in the number of coalescent
      histories is faster than exponential. Further, it provides a substantial
      improvement on the lower bound for the ratio of the largest number of matching
      coalescent histories to the smallest number of matching coalescent histories for
      trees with m taxa, increasing a previous bound of [Formula: see text] to
      [Formula: see text]. We discuss the implications of our enumerative results for
      phylogenetic computations.

PMID- 25973634
TI  - Visible-light induced isoindoles formation to trigger intermolecular Diels-Alder
      reactions in the presence of air.
AB  - Visible-light induced isoindole formation triggered an intermolecular Diels-Alder
      reaction with dienophiles such as acetylenedicarboxylate and maleimides in the
      presence of air. The reaction resulted in excellent diastereoselctivity and high
      yields under mild reaction conditions. This protocol provides an atom-economical,
      transition-metal-free (TM-free) and straightforward approach to structurally
      diverse bridged-ring heterocycles from easily accessible molecules. 

PMID- 25973635
TI  - Detecting single-trial EEG evoked potential using a wavelet domain linear mixed
      model: application to error potentials classification.
AB  - OBJECTIVE: The main goal of this work is to develop a model for multisensor
      signals, such as magnetoencephalography or electroencephalography (EEG) signals
      that account for inter-trial variability, suitable for corresponding binary
      classification problems. An important constraint is that the model be simple
      enough to handle small size and unbalanced datasets, as often encountered in BCI
      type experiments. APPROACH: The method involves the linear mixed effects
      statistical model, wavelet transform, and spatial filtering, and aims at the
      characterization of localized discriminant features in multisensor signals. After
      discrete wavelet transform and spatial filtering, a projection onto the relevant
      wavelet and spatial channels subspaces is used for dimension reduction. The
      projected signals are then decomposed as the sum of a signal of interest (i.e.,
      discriminant) and background noise, using a very simple Gaussian linear mixed
      model. MAIN RESULTS: Thanks to the simplicity of the model, the corresponding
      parameter estimation problem is simplified. Robust estimates of class-covariance
      matrices are obtained from small sample sizes and an effective Bayes plug-in
      classifier is derived. The approach is applied to the detection of error
      potentials in multichannel EEG data in a very unbalanced situation (detection of
      rare events). Classification results prove the relevance of the proposed approach
      in such a context. SIGNIFICANCE: The combination of the linear mixed model,
      wavelet transform and spatial filtering for EEG classification is, to the best of
      our knowledge, an original approach, which is proven to be effective. This paper
      improves upon earlier results on similar problems, and the three main ingredients
      all play an important role.

PMID- 25973636
TI  - Epitaxial growth of a single-crystal hybridized boron nitride and graphene layer
      on a wide-band gap semiconductor.
AB  - Vertical and lateral heterogeneous structures of two-dimensional (2D) materials
      have paved the way for pioneering studies on the physics and applications of 2D
      materials. A hybridized hexagonal boron nitride (h-BN) and graphene lateral
      structure, a heterogeneous 2D structure, has been fabricated on single-crystal
      metals or metal foils by chemical vapor deposition (CVD). However, once
      fabricated on metals, the h-BN/graphene lateral structures require an additional
      transfer process for device applications, as reported for CVD graphene grown on
      metal foils. Here, we demonstrate that a single-crystal h-BN/graphene lateral
      structure can be epitaxially grown on a wide-gap semiconductor, SiC(0001). First,
      a single-crystal h-BN layer with the same orientation as bulk SiC was grown on a
      Si-terminated SiC substrate at 850  degrees C using borazine molecules. Second,
      when heated above 1150  degrees C in vacuum, the h-BN layer was partially removed
      and, subsequently, replaced with graphene domains. Interestingly, these graphene
      domains possess the same orientation as the h-BN layer, resulting in a single
      crystal h-BN/graphene lateral structure on a whole sample area. For temperatures
      above 1600  degrees C, the single-crystal h-BN layer was completely replaced by
      the single-crystal graphene layer. The crystalline structure, electronic band
      structure, and atomic structure of the h-BN/graphene lateral structure were
      studied by using low energy electron diffraction, angle-resolved photoemission
      spectroscopy, and scanning tunneling microscopy, respectively. The h-BN/graphene
      lateral structure fabricated on a wide-gap semiconductor substrate can be
      directly applied to devices without a further transfer process, as reported for
      epitaxial graphene on a SiC substrate. 

PMID- 25973637
TI  - Polymer Coatings in 3D-Printed Fluidic Device Channels for Improved Cellular
      Adherence Prior to Electrical Lysis.
AB  - This paper describes the design and fabrication of a polyjet-based three
      dimensional (3D)-printed fluidic device where poly(dimethylsiloxane) (PDMS) or
      polystyrene (PS) were used to coat the sides of a fluidic channel within the
      device to promote adhesion of an immobilized cell layer. The device was designed
      using computer-aided design software and converted into an .STL file prior to
      printing. The rigid, transparent material used in the printing process provides
      an optically transparent path to visualize endothelial cell adherence and
      supports integration of removable electrodes for electrical cell lysis in a
      specified portion of the channel (1 mm width * 0.8 mm height * 2 mm length).
      Through manipulation of channel geometry, a low-voltage power source (500 V max)
      was used to selectively lyse adhered endothelial cells in a tapered region of the
      channel. Cell viability was maintained on the device over a 5 day period (98%
      viable), though cell coverage decreased after day 4 with static media delivery.
      Optimal lysis potentials were obtained for the two fabricated device geometries,
      and selective cell clearance was achieved with cell lysis efficiencies of 94 and
      96%. The bottleneck of unknown surface properties from proprietary resin use in
      fabricating 3D-printed materials is overcome through techniques to incorporate
      PDMS and PS. 

PMID- 25973638
TI  - Molecular-Level Insights into Orientation-Dependent Changes in the Thermal
      Stability of Enzymes Covalently Immobilized on Surfaces.
AB  - Surface-immobilized enzymes are important for a wide range of technological
      applications, including industrial catalysis, drug delivery, medical diagnosis,
      and biosensors; however, our understanding of how enzymes and proteins interact
      with abiological surfaces on the molecular level remains extremely limited. We
      have compared the structure, activity, and thermal stability of two variants of a
      beta-galactosidase attached to a chemically well-defined maleimide-terminated
      self-assembled monolayer surface through a unique cysteinyl residue. In one case
      the enzyme is attached through an alpha helix and in the other case through an
      adjacent loop. Both enzymes exhibit similar specific activities and adopt similar
      orientations with respect to the surface normal, as determined by sum-frequency
      generation and attenuated total reflectance FT-IR spectroscopies. Surprisingly,
      however, the loop-tethered enzyme exhibits a thermal stability 10  degrees C
      lower than the helix-tethered enzyme and 13  degrees C lower than the enzyme in
      free solution. Using coarse-grain models, molecular dynamics simulations of the
      thermal unfolding of the surface-tethered enzymes were able to reproduce these
      differences in stability. Thus, revealing that tethering through the more
      flexible loop position provides more opportunity for surface residues on the
      protein to interact with the surface and undergo surface-induced unfolding. These
      observations point to the importance of the location of the attachment point in
      determining the performance of surface-supported biocatalysts and suggest
      strategies for optimizing their activity and thermal stability through molecular
      simulations. 

PMID- 25973639
TI  - Palladium-Catalyzed Oxidative O-H/N-H Carbonylation of Hydrazides: Access to
      Substituted 1,3,4-Oxadiazole-2(3H)-ones.
AB  - A novel palladium-catalyzed oxidative annulation reaction for the C-O, C-N bond
      formations is developed. The intramolecular cyclocarbonylation provides an
      efficient and direct approach for the construction of valuable 1,3,4-oxadiazole
      2(3H)-ones and their derivatives. The reaction also facilitated the convenient
      synthesis of BMS-191011, an opener of the cloned large-conductance Ca(2+)
      activated potassium channel, providing an attractive method for medicinal
      chemistry. 

PMID- 25973640
TI  - Glycosaminoglycan and versican deposits in taxane-induced sclerosis.
AB  - Docetaxel and paclitaxel are widely used in the treatment of various malignant
      neoplasms. Taxane-induced sclerosis is dose-dependent and usually not
      generalized. Little information on the pathogenesis of scleroderma is currently
      available. Here, we report a case of generalized scleroderma and a case of early
      stage oedematous sclerosis, both of which presented with intense versican
      deposits after administration of taxane for angiosarcoma. 

PMID- 25973641
TI  - Extinction of alcohol seeking is enhanced by compound extinction and the
      noradrenaline reuptake inhibitor atomoxetine.
AB  - Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even
      after extended periods of abstinence. Extinction of such stimuli provides a means
      for reducing their impact on relapse. However, the expression of extinction can
      be disrupted by exposure to the previous reinforcer as well as the simple passage
      of time. We investigated whether augmentation of prediction error or of
      noradrenaline neurotransmission by the reuptake inhibitor atomoxetine would
      enhance long-term extinction of alcohol-seeking behavior. Rats received Pavlovian
      conditioning of multiple stimuli signaling the delivery of an alcohol reward
      before individual extinction was given to each of these stimuli. Further
      extinction was then given to a target stimulus presented in compound with another
      alcohol-predictive stimulus intended to augment prediction error (Experiment 1)
      or after a systemic injection of atomoxetine (1.0 mg/kg; Experiment 2).
      Experiment 3 examined whether the compound stimulus effect relied on
      noradrenergic activity by testing the effects of the beta-adrenergic antagonist
      propranolol, given prior to compound stimulus trials. Long-term retention of
      extinction learning was assessed a week later. Compound stimulus presentations
      enhanced long-term extinction as the stimulus extinguished in compound elicited
      less responding than a stimulus receiving equal extinction alone when tested a
      week later. This effect was mimicked by atomoxetine and blocked by propranolol
      given during extinction training. Thus, extinction of alcohol-seeking behavior
      can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing
      noradrenaline neurotransmission during extinction training. Both behavioral and
      neurobiological processes could be exploited to enhance the outcome of extinction
      based treatments for alcohol use disorders.

PMID- 25973642
TI  - Risk factors for renal disease in systemic lupus erythematosus and their clinical
      implications.
AB  - Lupus nephritis is one of the most common severe manifestations of systemic lupus
      erythematosus and is associated with significant morbidity and mortality.
      Genetic, ethnic and hormonal factors may influence the presence and severity of
      renal involvement and therefore affect the outcome and overall prognosis of
      patients. In this review, we will discuss the association of known lupus risk
      factors in developing renal disease and explore the recent literature to identify
      potential risk factors and their clinical implications in terms of diagnostic
      vigilance, management and prognosis. 

PMID- 25973643
TI  - Synergistic protective effect of folic acid and vitamin B12 against nicotine
      induced oxidative stress and apoptosis in pancreatic islets of the rat.
AB  - CONTEXT: Nicotine is an abundant and most significant component of cigarette
      smoke. Epidemiological evidence strongly suggests an association between
      cigarette smoking and pancreatic injury, although effects of smoking on endocrine
      pancreas are still controversial. OBJECTIVE: We examined the impact and
      underlying mechanisms of action of folic acid and vitamin B12 on nicotine-induced
      damage in pancreatic islets of rats. MATERIALS AND METHODS: Male Wistar rats were
      treated with nicotine (3 mg/kg body weight/d, intraperitonealy) with or without
      folic acid (36 ug/kg body weight/d, orally) and vitamin B12 (0.63 ug/kg body
      weight/d, orally) for 21 d. Fasting blood glucose, oral glucose tolerance test,
      HBA1c, insulin, oxidative stress parameters, proinflammatory cytokines, and CRP
      level were measured. Histological evaluation, TUNEL assay, and
      immunohistochemical staining of NF-kappaB and caspase-3 were also performed.
      RESULTS: Folic acid and vitamin B12 blunted the nicotine-induced impairment in
      fasting blood glucose (51-56% recovery), HbA1c (64-76% recovery), oral glucose
      tolerance, insulin level (23-40% recovery), and islet cell counts (26-74%
      recovery) in rats. Moreover, folic acid in combination with vitamin B12 also
      attenuated the nicotine-induced changes in markers of oxidative stress (17-88%
      recovery), TNF-alpha (40-99% recovery), and IL-6 level (47-65% recovery), CRP
      level (59-73% recovery), expression of NF-kappaB and caspase-3, and apoptosis in
      pancreatic islet cells. DISCUSSION AND CONCLUSION: The present study shows that
      folic acid and vitamin B12 supplementation can reduce nicotine-induced impairment
      in glucose homeostasis and apoptosis and damage of pancreatic islet cells by
      modulating oxidative stress, levels of proinflammatory cytokines, and expression
      of NF-kappaB.

PMID- 25973644
TI  - Protective effect of Salacia oblonga against tobacco smoke-induced DNA damage and
      cellular changes in pancreatic beta-cells.
AB  - CONTEXT: Tobacco smoking generates a tremendous amount of free radicals that
      induce oxidative stress (OS) in diabetics (pancreatic islet cells are defective).
      Salacia oblonga Wall. (Celastraceae) is a proven antioxidant and antidiabetic
      plant whose mechanism of action is yet to be explored. OBJECTIVE: The present
      study focuses on the protective ability of S. oblonga in tobacco smoke-induced
      oxidatively stressed pancreatic beta-cell line. MATERIALS AND METHODS: The RINm5f
      cell line was exposed to tobacco smoke concentrate (TSC) (0.5-10%, 24 h), plant
      extract (1-75 ug/ml, 3 h), and their combinations. Cell viability was determined
      through MTT assay. Microscopic analysis was carried out in unstained and nonyl
      acridine orange-stained cells. The effect of toxic doses of TSC on DNA integrity
      was analyzed through DNA fragmentation assay. The TSC-induced nitric oxide
      generation was determined spectrophototmetrically. The expression of anti
      apoptotic protein Bcl-X under the above treatment conditions was carried out
      through RT-PCR. RESULTS: The LD50 dose for TSC was found to be 1% TSC. Salacia
      oblonga extracts (10 and 15 ug/ml) were found to be optimum safe doses that
      significantly increased cell viability and decreased the nitric oxide production
      in TSC-treated cells. Pre-treatment with plant extract suppressed apoptosis
      through probable increase in the expression of anti-apoptotic protein Bcl-X in
      TSC-treated cells. Thus, the overall efficiency of plant extract in recovering
      cellular damage was proven. DISCUSSION AND CONCLUSION: The results suggest that
      TSC-induced cellular alterations are related to rise in nitric oxide and Bcl-X
      mRNA expression and propose that S. oblonga may confer significant cytoprotection
      against OS-mediated injury in beta-cells.

PMID- 25973645
TI  - DAAB: a manually curated database of allergy and asthma biomarkers.

PMID- 25973646
TI  - Research without borders: fostering innovative clinical research and
      implementation.
AB  - Stroke remains one of the major killers worldwide. Addressing this epidemic will
      require combined efforts of researchers (bench, translational, clinical,
      epidemiologists, outcomes, and implementation scientists) as well as all forms of
      health care workers and policy experts. However, the translation of bench
      findings into bedside has been a challenge. Improved strategies for clinical
      research are needed to shorten the time required to translate bench findings into
      patient care. Large national or even globe stroke registries are uniquely
      positioned to advance the science by providing a rich data source for disease and
      post marketing surveillance, comparative effectiveness and safety research, and
      ultimately dissemination of clinical trials findings to routine clinical
      practice. Fostering innovative clinical research and implementation through
      international collaborations provides an unprecedented opportunity to tackle the
      globe of stroke. 

PMID- 25973647
TI  - Hepatic fibrosis assessed using transient elastography independently associated
      with coronary artery calcification.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has a close
      relationship with coronary atherosclerosis. We investigated the association
      between coronary atherosclerosis and liver fibrosis, represented as coronary
      artery calcification (CAC) score, and live stiffness (LS) value assessed using
      transient elastography (TE), respectively, in patients with NAFLD. METHODS:
      Between January 2013 and March 2014, a total of 285 asymptomatic subjects without
      chronic liver and ischemic heart diseases who underwent comprehensive medical
      health check-up were recruited. NAFLD was defined as controlled attenuation
      parameter (CAP) >= 250 dB/m on TE. RESULTS: The median age of the study
      population (men 161 and women 124) was 56 (interquartile [IQR], 50-63) years. Of
      these, 142 (49.8%) subjects had NAFLD. Among subjects with NAFLD, CAC score was
      independently correlated with the male gender (beta = 0.230; P = 0.010), elevated
      erythrocyte sedimentation rate (beta = 0.220; P = 0.019), reduced estimated
      glomerular filtration rate (beta=-0.220; P = 0.004), increased left ventricular
      mass index (beta = 0.226; P = 0.027), and higher LS values (beta = 0.274; P <
      0.001). In addition, alanine aminotransferase level (beta = 0.214, P = 0.012) and
      CAC score (beta = 0.311; P = 0.001) are the only independent factors associated
      with LS values in subjects with NAFLD. CONCLUSIONS: Higher CAC score was
      independently correlated with LS values in subjects with NAFLD. However, it
      should be further investigated whether TE can be incorporated into a screening
      tool to identify the high-risk population for coronary artery disease.

PMID- 25973648
TI  - Chemical Descriptors of Yttria-Stabilized Zirconia at Low Defect Concentration:
      An ab Initio Study.
AB  - Yttria-stabilized zirconia (YSZ) is an important oxide ion conductor with
      applications in solid oxide fuel cells (SOFCs) and oxygen sensing devices. Doping
      the cubic phase of zirconia (c-ZrO2) with yttria (Y2O3) is isoelectronic, as two
      Zr(4+) ions are replaced by two Y(3+) ions, plus a charge compensating oxygen
      vacancy (Ovac). Typical doping concentrations include 3, 8, 10, and 12 mol %. For
      these concentrations, and all below 40 mol %, no phase with long-range order has
      been observed in either X-ray or neutron diffraction experiments. The prediction
      of local defect structure and the interaction between defects is therefore of
      great interest. This has not been possible to date as the number of possible
      defect topologies is very large and to perform reliable total energy calculations
      for all of them would be prohibitively expensive. Previous theoretical studies
      have only considered a selection of representative structures. In this study, a
      comprehensive search for low-energy defect structures using a combined classical
      modeling and density functional theory approach is used to identify the low
      energy isolated defect structures at the dilute limit, 3.2 mol %. Through
      analysis of energetics computed using the best available Born-Mayer-Huggins
      empirical potential model, a point charge model, DFT, and a local strain energy
      estimated in the harmonic approximation, the main chemical and physical
      descriptors that correlate to the low-energy DFT structures are discussed. It is
      found that the empirical potential model reproduces a general trend of increasing
      DFT energetics across a series of locally strain relaxed structures but is
      unreliable both in predicting some incorrect low-energy structures and in finding
      some metastable structures to be unstable. A better predictor of low-energy
      defect structures is found to be the total electrostatic energy of a simple point
      charge model calculated at the unrelaxed geometries of the defects. In addition,
      the strain relaxation energy is estimated effectively in the harmonic
      approximation to the imaginary phonon modes of undoped c-ZrO2 but is found to be
      unimportant in determining the low-energy defect structures. These results allow
      us to propose a set of easily computed descriptors that can be used to identify
      the low-energy YSZ defect structures, negating the combinatorial complexity and
      number of defect structures that need to be considered. 

PMID- 25973649
TI  - Weekly Cycles in Daily Report Data: An Overlooked Issue.
AB  - Daily diaries and other everyday experience methods are increasingly used to
      study relationships between two time-varying variables X and Y. Although daily
      data potentially often have weekly cyclical patterns (e.g., stress may be higher
      on weekdays and lower on weekends), the majority of daily diary studies have
      ignored this possibility. In this study, we investigated the effect of ignoring
      existing weekly cycles. We reanalyzed an empirical dataset (stress and alcohol
      consumption) and performed Monte Carlo simulations to investigate the impact of
      omitting weekly cycles. In the empirical dataset, ignoring cycles led to the
      inference of a significant within-person X-Y relation whereas modeling cycles
      suggested that this relationship did not exist. Simulation results indicated that
      ignoring cycles that existed in both X and Y led to bias in the estimated within
      person X-Y relationship. The amount and direction of bias depended on the
      magnitude of the cycles, magnitude of the true within-person X-Y relation, and
      synchronization of the cycles. We encourage researchers conducting daily diary
      studies to address potential weekly cycles in their data. We provide guidelines
      for detecting and modeling cycles to remove their influence and discuss
      challenges of causal inference in daily experience studies.

PMID- 25973650
TI  - Chronic Traumatic Thoracic Aortic Aneurysm: 40-Year Follow-Up.
AB  - Traumatic aortic injury is a rare but potentially lethal condition. Those few
      patients who survive the acute phase of injury usually progress to form a chronic
      aneurysm. Few guidelines exist on the management of chronic traumatic aortic
      aneurysms. Here, we describe the conservative management of a patient with a
      traumatic thoracic aortic aneurysm who has remained asymptomatic for 40 years.

PMID- 25973651
TI  - Stimulation of cutaneous wound healing by an FPR2-specific peptide agonist
      WKYMVm.
AB  - Diabetes is one of the most common human diseases and 15% of the 200 million
      diabetics worldwide suffer from diabetic wounds. Development of new therapeutic
      agents is needed for treatment of diabetic wounds. Wound healing is mediated by
      multiple steps, including inflammation, epithelialization, neoangiogenesis, and
      granulation. Formyl peptide receptor 2 has been known to stimulate angiogenesis,
      which is essential for tissue repair and cutaneous wound healing. In this study,
      we explored the therapeutic effects of WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2), a
      synthetic peptide agonist of formyl peptide receptor 2, on cutaneous wounds in
      streptozotocin-induced diabetic rats. Topical application of WKYMVm onto
      cutaneous wounds stimulated formation of von Willebrand factor-positive capillary
      and alpha-smooth muscle actin-positive arteriole with a maximal stimulation on
      day 6, suggesting WKYMVm-stimulated angiogenesis. Infiltration of immune cells
      could be detected on early phase during wound healing and WKYMVm treatment
      acutely augmented infiltration of CD68-positive macrophages. In addition,
      reepithelialization and granulation tissue formation were accelerated by
      treatment with WKYMVm. These results suggest that WKYMVm has therapeutic effects
      on diabetic wounds by stimulating angiogenesis and infiltration of immune cells. 

PMID- 25973653
TI  - A growing focus on bacterial individuality.

PMID- 25973652
TI  - An update on Anti-inflammatory Compounds: A Review.
AB  - Inflammation is a protective attempt by the organism to remove the injurious
      stimuli and to initiate the healing process. Also, it has been reported to be
      associated with the onset of various cancers. An effective anti-inflammatory drug
      should be able to inhibit the development of inflammation without interfering in
      normal homeostasis. Current approaches to overcome the inflammation include the
      use of immune selective anti-inflammatory derivatives, selective glucocorticoid
      receptor agonist, resolvins and protectins and TNF inhibitors. A number of herbal
      drugs have been identified in the past that can target inflammatory cytokines.
      This review mainly focuses on the newer molecules to combat the inflammation and
      also emphasise on various studies carried out in the past. Thus, the high
      prevalence of inflammation obliges the development of new drugs; therefore, a
      safe and efficient drug molecule to confer protection against inflammation is
      urgently needed. 

PMID- 25973654
TI  - Amino acid-based cationic lipids with alpha-tocopherol hydrophobic tail for
      efficient gene delivery.
AB  - In this work, three amino acid-based cationic lipids L1-L3 bearing the same alpha
      tocopherol moiety and biodegradable ester bond linkage, but differing in the
      polar head-group, were prepared and applied as non-viral gene delivery vectors.
      The physicochemical properties such as size, zeta-potential, stability, and
      cellular uptake of the lipoplexes formed from lipids L1-L3 as well as the
      transfection efficacy (TE) were investigated. The results showed that the
      chemical composition of the cationic head-group clearly affects the
      physicochemical parameters of the amino acid-based lipids, especially the TE.
      Besides their low cytotoxicity, these lipoplexes also showed comparable TE to
      commercially available lipofectamine 2000. In particular, dipeptide lipid L3 gave
      excellent TE, which was 1.8 times higher than bPEI 25k in the presence of 10%
      serum in Hela cells. These results demonstrate the promising use of novel
      dipeptide lipids for safe and efficient gene delivery. 

PMID- 25973655
TI  - Influence of structural isomerism and fluorine atom substitution on the self
      association of naphthoic acid.
AB  - The self-association of small aromatic systems driven by pi-pi stacking and
      hydrophobic interactions is well-known. Understanding the nature of these
      interactions is important if they are to be used to control association. Here, we
      present results of an NMR study into the self-association of two isomers of
      naphthoic acid along with an investigation into the role of a fluorine
      substituent on that self-association. We interpret the results in terms of a
      simple isodesmic model of self-association and show that the addition of the
      fluorine atom appears to increase the stability of the aggregates by an order of
      magnitude (e.g., 1-naphthoic acid vs 4-fluoro-1-naphthoic acid, Keq = 0.05
      increases to 0.35 M(-1)), a result which is supported by computational studies in
      the literature on the role of substituent effects on interaction energy. The use
      of fluorinated isomers to probe the assembly is also presented, with differing
      trends in fluorine-19 chemical shifts observed depending on the isomer
      substitution pattern. 

PMID- 25973657
TI  - WSACS--The Abdominal Compartment Society. A Society dedicated to the study of the
      physiology and pathophysiology of the abdominal compartment and its interactions
      with all organ systems.

PMID- 25973658
TI  - How to deal with an open abdomen?
AB  - Appropriate open abdomen treatment is one of the key elements in the management
      of patients who require decompressive laparotomy or in whom the abdomen is left
      open prophylactically. Apart from fluid control and protection from external
      injury, fluid evacuation and facilitation of early closure are now the goals of
      open abdomen treatment. Abdominal negative pressure therapy has emerged as the
      most appropriate method to reach these goals. Especially when combined with
      strategies that allow progressive approximation of the fascial edges, high
      closure rates can be obtained. Intra-abdominal pressure measurement can be used
      to guide the surgical strategy and continued attention to intra-abdominal
      hypertension is necessary. This paper reviews recent advances as well as
      identifying the remaining challenges in patients requiring open abdomen
      treatment. The new classification system of the open abdomen is an important tool
      to use when comparing the efficacy of different strategies, as well as different
      systems of temporary abdominal closure. 

PMID- 25973659
TI  - Intra-abdominal hypertension and abdominal compartment syndrome in burns,
      obesity, pregnancy, and general medicine.
AB  - Intra-abdominal hypertension (IAH) is an important contributor to early organ
      dysfunction in trauma and sepsis. However, relatively little is known about the
      impact of intra-abdominal pressure (IAP) in general internal medicine, pregnant
      patients, and those with obesity or burns. The aim of this paper is to review the
      pathophysiologic implications and treatment options for IAH in these specific
      situations. A MEDLINE and PubMed search was performed and the resulting body-of
      evidence included in the current review on the basis of relevance and scientific
      merit. There is increasing awareness of the role of IAH in different clinical
      situations. Specifically, IAH will develop in most (if not all) severely burned
      patients, and may contribute to early mortality. One should avoid over
      resuscitation of these patients with large volumes of fluids, especially
      crystalloids. Acute elevations in IAP have similar effects in obese patients
      compared to non-obese patients, but the threshold IAP associated with organ
      dysfunction may be higher. Chronic elevations in IAP may, in part, be responsible
      for the pathogenesis of obesity-related co-morbid conditions such as
      hypertension, pseudotumor cerebri, pulmonary dysfunction, gastroesophageal reflux
      disease, and abdominal wall hernias. At the bedside, measuring IAP and
      considering IAH in all critical maternal conditions is essential, especially in
      preeclampsia/eclampsia where some have hypothesized that IAH may have an
      additional role. IAH in pregnancy must take into account the precautions for
      aorto-caval compression and has been associated with ovarian hyperstimulation
      syndrome. Recently, IAP has been associated with the cardiorenal dilemma and
      hepatorenal syndrome, and this has led to the recognition of the polycompartment
      syndrome. In conclusion, IAH and ACS have been associated with several patient
      populations beyond the classical ICU, surgical, and trauma patients. In all at
      risk conditions the focus should be on the early recognition of IAH and
      prevention of ACS. Patients at risk for IAH should be identified early through
      measurements of IAP. Appropriate actions should be taken when IAP increases above
      15 mm Hg, especially if pressures reach above 20 mm Hg with new onset organ
      failure. Although non-operative measures come first, surgical decompression must
      not be delayed if these fail. Percutaneous drainage of ascites is a simple and
      potentially effective tool to reduce IAP if organ dysfunction develops,
      especially in burn patients. Escharotomy may also dramatically reduce IAP in the
      case of abdominal burns. 

PMID- 25973660
TI  - Intra-abdominal hypertension and abdominal compartment syndrome in pancreatitis,
      paediatrics, and trauma.
AB  - Intra-abdominal hypertension (IAH) is an important contributor to early organ
      dysfunction among patients with trauma and sepsis. However, the impact of
      increased intra-abdominal pressure (IAP) among pediatric, pregnant, non-septic
      medical patients, and those with severe acute pancreatitis (SAP), obesity, and
      burns has been studied less extensively. The aim of this review is to outline the
      pathophysiologic implications and treatment options for IAH and abdominal
      compartment syndrome (ACS) for the above patient populations. We searched MEDLINE
      and PubMed to identify relevant studies. There is an increasing awareness of IAH
      in general medicine. The incidence of IAH and, to a lesser extent, ACS is high
      among patients with SAP. IAH should always be suspected and IAP measured
      routinely. In children, normal IAP in mechanically ventilated patients is
      approximately 7 +/- 3 mm Hg. As an IAP of 10-15 mm Hg has been associated with
      organ damage in children, an IAP greater than 10 mm Hg should be considered IAH
      in these patients. Moreover, as ACS may occur in children at an IAP lower than 20
      mm Hg, any elevation in IAP higher than 10 mm Hg associated with new organ
      dysfunction should be considered ACS in children until proven otherwise. Monitor
      IAP trends and be aware that specific interventions may need to be instituted at
      lower IAP than the current ACS definitions accommodate. Finally, IAH and ACS can
      occur both in abdominal trauma and extra-abdominal trauma patients. Early
      mechanical hemorrhage control and the avoidance of excessive fluid resuscitation
      are key elements in preventing IAH in trauma patients. IAH and ACS have been
      associated with many conditions beyond the general ICU patient. In adults and in
      children, the focus should be on the early recognition of IAH and the prevention
      of ACS. Patients at risk for IAH should be identified early during their
      treatment (with a low threshold to initiate IAP monitoring). Appropriate actions
      should be taken when IAP increases above 20 mm Hg, especially in patients
      developing difficulty with ventilation. Although on-operative measures should be
      instituted first, one should not hesitate to resort to surgical decompression if
      they fail. 

PMID- 25973661
TI  - A user's guide to intra-abdominal pressure measurement.
AB  - The intra-abdominal pressure (IAP) measurement is a key to diagnosing and
      managing critically ill medical and surgical patients. There are an increasing
      number of techniques that allow us to measure the IAP at the bedside. This paper
      reviews these techniques. IAP should be measured at end-expiration, with the
      patient in the supine position and ensuring that there is no abdominal muscle
      activity. The intravesicular IAP measurement is convenient and considered the
      gold standard. The level where the mid-axillary line crosses the iliac crest is
      the recommended zero reference for the transvesicular IAP measurement; moreover,
      marking this level on the patient increases reproducibility. Protocols for IAP
      measurement should be developed for each ICU based on the locally available tools
      and equipment. IAP measurement techniques are safe, reproducible and accurate and
      do not increase the risk of urinary tract infection. Continuous IAP measurement
      may offer benefits in specific situations in the future. In conclusion, the IAP
      measurement is a reliable and essential adjunct to the management of patients at
      risk of intra-abdominal hypertension. 

PMID- 25973663
TI  - What every ICU clinician needs to know about the cardiovascular effects caused by
      abdominal hypertension.
AB  - The effects of increased intra-abdominal pressure (IAP) on cardiovascular
      function are well recognized and include a combined negative effect on preload,
      afterload and contractility. The aim of this review is to summarize the current
      knowledge on this topic. The presence of intra-abdominal hypertension (IAH)
      erroneously increases barometric filling pressures like central venous (CVP) and
      pulmonary artery occlusion pressure (PAOP) (since these are zeroed against
      atmospheric pressure). Transmural filling pressures (calculated by subtracting
      the pleural pressure from the end-expiratory CVP value) may better reflect the
      true preload status but are difficult to obtain at the bedside. Alternatively,
      since pleural pressures are seldom measured, transmural CVP can also be estimated
      by subtracting half of the IAP from the end-expiratory CVP value, since
      abdominothoracic transmission is on average 50%. Volumetric preload indicators,
      such as global and right ventricular end-diastolic volumes or the left
      ventricular end-diastolic area, also correlate better with true preload. When
      using functional hemodynamic monitoring parameters like stroke volume variation
      (SVV) or pulse pressure variation (PPV) one must bear in mind that increased IAP
      will increase these values (via a concomitant increase in intrathoracic
      pressure). The passive leg raising test may be a false negative in IAH.
      Calculation of the abdominal perfusion pressure (as mean arterial pressure minus
      IAP) has been shown to be a better resuscitation endpoint than IAP alone.
      Finally, it is re-assuring that transpulmonary thermodilution techniques have
      been validated in the setting of IAH and abdominal compartment syndrome. In
      conclusion, the clinician must be aware of the different effects of IAH on
      cardiovascular function in order to assess the volume status accurately and to
      optimize hemodynamic performance. 

PMID- 25973662
TI  - Management of abdominal sepsis--a paradigm shift?
AB  - The abdomen is the second most common source of sepsis and secondary peritonitis.
      The most common causes of abdominal sepsis are perforation, ischemic necrosis or
      penetrating injury to the abdominal viscera. Management consists of control of
      the infection source, restoration of gastrointestinal tract (GI) function,
      systemic antimicrobial therapy and support of organ function. Mortality after
      secondary peritonitis is still high. Excluding patient-related factors such as
      age or co-morbidities that can not be influenced at the time of intervention,
      delay to surgical intervention and inability to obtain source control are the
      main determinants of outcome. In patients with severe physiological derangement
      or difficult intraperitoneal conditions, where a prolonged operation and complete
      anatomical repair may not be possible or appropriate, it is becoming increasingly
      popular to utilize a damage control strategy with abbreviated laparotomy and
      planned reoperations. The main components of damage control laparotomy for
      secondary peritonitis are postponing the reconstruction of intestinal anastomoses
      to a second operation (deferred anastomosis) and leaving the abdomen open with
      some form of temporary abdominal closure (TAC). Advances in the management
      techniques of the open abdomen and new negative pressure-based TAC-devices have
      significantly reduced the previously observed prohibitive morbidity associated
      with open abdomens. These advancements have led to current fascial closure rates
      after TAC approaching 90%. The cornerstones of appropriate antimicrobial therapy
      are the timing, spectrum and dosing of antibiotics. Enteral nutrition should be
      started as soon as possible in hemodynamically stable patients but withheld when
      the patient is on a significant dose of vasopressors or whenever GI hypoperfusion
      is suspected. Timely source control with appropriate use of antimicrobial agents
      and early intensive care offers the best chance of survival for patients with
      abdominal sepsis. The introduction of the concept of damage control to the
      management of secondary peritonitis represents a paradigm shift in the same way
      as in management of major trauma. Although limited and repeated surgical
      interventions have been shown to be safe, the actual benefits need to be
      demonstrated in controlled studies. 

PMID- 25973664
TI  - Abdominal signs and symptoms in intensive care patients.
AB  - Abdominal problems, both as a primary reason for admission or developing as a
      part of multiple organ dysfunction syndrome during an ICU stay, are common in
      critically ill patients. The definitions, assessment, incidence and outcome of
      different abdominal signs, symptoms and syndromes are assessed in the current
      review. General abdominal signs and symptoms include abdominal pain and
      distension, as well as other signs assessed during the physical examination (e.g.
      palpation, percussion). Gastrointestinal (GI) symptoms include vomiting, high
      gastric residual volumes, diarrhoea, GI bleeding, paralysis of the lower GI
      tract, bowel dilatation and absent bowel sounds. Although around half of patients
      suffer from these symptoms, the reported incidences of single symptoms vary
      within a large range due to variable definitions and case-mix. In a few studies,
      the total number of coincident GI symptoms was associated with increased
      mortality. Although acute abdomen is a well-recognized severe syndrome in
      emergency medicine, its incidence in ICUs is not known. Next to subjective
      clinical evaluation, intra-abdominal pressure, as a reproducible numerical
      variable, provides useful assistance in the assessment of the abdominal
      compartment, whereas intra-abdominal hypertension has been shown to impair the
      outcome of the critically ill. In conclusion, abdominal symptoms occur in half of
      patients in ICUs. Clinical evaluation, albeit largely subjective, remains the
      main bedside tool to detect abdominal problems and to assess GI function in the
      critically ill. IAP is a useful additional tool in the assessment of abdominal
      complications in ICUs. 

PMID- 25973665
TI  - TPEN prevents rapid pacing-induced calcium overload and nitration stress in HL-1
      myocytes.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia.
      However, the current drug interference of antiarrhythmia has limited efficacy and
      off-target effects. Accumulating evidence has implicated a potential role of
      nitration stress in the pathogenesis of AF. The aim of the study was to determine
      whether TPEN provided antinitration effects on atrial myocytes during AF,
      especially under circumstances of nitration stress. METHODS: We utilized a rapid
      paced HL-1 cells model for AF. The changes of electrophysiological
      characteristics and structure of paced HL-1 cells were determined by a patch
      clamp and a TEM method. The effects of TPEN on pacing and ONOO(-) pretreated HL-1
      cells were examined using MTT assay, TUNEL technique, confocal microscope
      experiment, and Western blot analysis. RESULTS: The results revealed that ONOO(-)
      reduced the viability of HL-1 cells in a dose-dependent manner, and 1 MUmol/L
      TPEN significantly ameliorated the damage caused by 50 MUmol/L ONOO(-) (P <
      0.05). Pacing and/or ONOO(-) -induced marked shortening of APD, myolysis, and
      nuclear condensation. TPEN inhibited the Ca(2+) overload induced by rapid pacing
      (P < 0.05) and ONOO(-) stimulation (P < 0.05). The application of TPEN
      significantly prevented the protein nitration caused by pacing or pacing plus
      ONOO(-) (P < 0.05). Additionally, pacing in combination with ONOO(-) treatment
      led to increase in apoptosis in HL-1 cells (P < 0.01), which could be reduced by
      pretreatment with TPEN (P < 0.05). CONCLUSIONS: TPEN prevents Ca(2+) overload and
      nitration stress in HL-1 atrial myocytes during rapid pacing and circumstances of
      nitration stress.

PMID- 25973666
TI  - Deviations in human gut microbiota: a novel diagnostic test for determining
      dysbiosis in patients with IBS or IBD.
AB  - BACKGROUND: Dysbiosis is associated with many diseases, including irritable bowel
      syndrome (IBS), inflammatory bowel diseases (IBD), obesity and diabetes.
      Potential clinical impact of imbalance in the intestinal microbiota suggests need
      for new standardised diagnostic methods to facilitate microbiome profiling. AIM:
      To develop and validate a novel diagnostic test using faecal samples to profile
      the intestinal microbiota and identify and characterise dysbiosis. METHODS: Fifty
      four DNA probes targeting >=300 bacteria on different taxonomic levels were
      selected based on ability to distinguish between healthy controls and IBS
      patients in faecal samples. Overall, 165 healthy controls (normobiotic reference
      collection) were used to develop a dysbiosis model with a bacterial profile and
      Dysbiosis Index score output. The model algorithmically assesses faecal bacterial
      abundance and profile, and potential clinically relevant deviation in the
      microbiome from normobiosis. This model was tested in different samples from
      healthy volunteers and IBS and IBD patients (n = 330) to determine the ability to
      detect dysbiosis. RESULTS: Validation confirms dysbiosis was detected in 73% of
      IBS patients, 70% of treatment-naive IBD patients and 80% of IBD patients in
      remission, vs. 16% of healthy individuals. Comparison of deep sequencing and the
      GA-map Dysbiosis Test, (Genetic Analysis AS, Oslo, Norway) illustrated good
      agreement in bacterial capture; the latter showing higher resolution by targeting
      pre-determined highly relevant bacteria. CONCLUSIONS: The GA-map Dysbiosis Test
      identifies and characterises dysbiosis in IBS and IBD patients, and provides
      insight into a patient's intestinal microbiota. Evaluating microbiota as a
      diagnostic strategy may allow monitoring of prescribed treatment regimens and
      improvement in new therapeutic approaches.

PMID- 25973667
TI  - Anticancer Agents: Does a Phosphonium Behave Like a Gold(I) Phosphine Complex?
      Let a "Smart" Probe Answer!
AB  - Gold phosphine complexes, such as auranofin, have been recognized for decades as
      antirheumatic agents. Clinical trials are now underway to validate their use in
      anticancer or anti-HIV treatments. However, their mechanisms of action remain
      unclear. A challenging question is whether the gold phosphine complex is a
      prodrug that is administered in an inactive precursor form or rather that the
      gold atom remains attached to the phosphine ligand during treatment. In this
      study, we present two novel gold complexes, which we compared to auranofin and to
      their phosphonium analogue. The chosen ligand is a phosphine-based smart probe,
      whose strong fluorescence depends on the presence of the gold atom. The in vitro
      biological action of the gold complexes and the phosphonium derivative were
      investigated, and a preliminary in vivo study in healthy zebrafish larvae allowed
      us to evaluate gold complex biodistribution and toxicity. The different analyses
      carried out showed that these gold complexes were stable and behaved differently
      from phosphonium and auranofin, both in vitro and in vivo. Two-photon microscopy
      experiments demonstrated that the cellular targets of these gold complexes are
      not the same as those of the phosphonium analogue. Moreover, despite similar IC50
      values in some cancer cell lines, gold complexes displayed a low toxicity in
      vivo, in contrast to the phosphonium salt. They are therefore suitable for future
      in vivo investigations. 

PMID- 25973668
TI  - Interprofessional education as a method to address health needs in a Hispanic
      community setting: A pilot study.
AB  - The Hispanic population in and around Richmond, Virginia, USA, has grown rapidly
      since 2000. The Richmond City Latino Needs Assessment emphasized this growth and
      also reported concerns regarding healthcare access. Schools of medicine,
      pharmacy, and nursing at Virginia Commonwealth University have partnered together
      with community organizations to develop and implement an interprofessional
      student service learning pilot program to meet community needs and provide an
      opportunity for enhanced learning. Community events allowed students to work on
      interprofessional teams to provide healthcare screenings and education to the
      Hispanic community. The program was evaluated by the use of a community service
      survey. Results indicated improved perceptions of student comfort with working
      with diverse patients, working on teams, and patient-centered care, as well as
      statistically significant improvements in student understanding of health care
      access and barriers, community needs, and social determinants of health. Results
      suggest that this community-based service-learning interprofessional experience
      was critical in student learning. 

PMID- 25973669
TI  - Patients with Obstructive Sleep Apnea at Altitude.
AB  - Bloch, Konrad E., Tsogyal D. Latshang, and Silvia Ulrich. Patients with
      obstructive sleep apnea at altitude. High Alt Med Biol 16:110-116, 2015.-
      Obstructive sleep apnea (OSA) is highly prevalent in the general population, in
      particular in men and women of older age. In OSA patients sleeping near sea
      level, the apneas/hypopneas associated with intermittent hypoxemia are
      predominantly due to upper airway collapse. When OSA patients stay at altitudes
      above 1600 m, corresponding to that of many tourist destinations, hypobaric
      hypoxia promotes frequent central apneas in addition to obstructive events,
      resulting in combined intermittent and sustained hypoxia. This induces strong
      sympathetic activation with elevated heart rate, cardiac arrhythmia, and systemic
      hypertension. There are concerns that these changes expose susceptible OSA
      patients, in particular those with advanced age and co-morbidities, to an
      excessive risk of cardiovascular and other adverse events during a stay at
      altitude. Based on data from randomized trials, it seems advisable for OSA
      patients to use continuous positive airway pressure treatment with computer
      controlled mask pressure adjustment (autoCPAP) in combination with acetazolamide
      during an altitude sojourn. If CPAP therapy is not feasible, acetazolamide alone
      is better than no treatment at all, as it improves oxygenation and sleep apnea
      and prevents excessive blood pressure rises of OSA patients at altitude.

PMID- 25973671
TI  - Anxiety Assessment Should Be Added to Postpartum Depression Screening: A Research
      Letter.

PMID- 25973670
TI  - Comparison of lung expansion techniques on thoracoabdominal mechanics and
      incidence of pulmonary complications after upper abdominal surgery: a randomized
      and controlled trial.
AB  - OBJECTIVE: Lung expansion techniques (LETs) are widely used to prevent
      postoperative pulmonary complications (PPCs). However, the effects of each of
      these techniques on thoracoabdominal mechanics and PPC incidence after abdominal
      surgery remain unclear. The objective of this study was to compare the effects of
      LET on pulmonary volumes, respiratory muscle activation, and PPC incidence after
      major, elective upper abdominal surgery. METHODS: This randomized controlled
      trial enrolled 137 patients who were randomly assigned into four groups: control
      (n = 35), flow incentive spirometry (n = 33), deep breathing (n = 35), and volume
      incentive spirometry (n = 34). Each intervention was performed tid during 5
      consecutive days. Subsequently, PPCs (pneumonia, atelectasis, or severe
      hypoxemia) were analyzed by a blinded assessor until hospital discharge. Lung
      volumes (optoelectronic plethysmography) and inspiratory muscular activation
      (surface electromyography) were assessed before and 3 days after surgery.
      Intention-to-treat analysis was performed. RESULTS: Before surgery, all groups
      were homogenous for age, sex, BMI, lung function, and thoracoabdominal mechanics.
      After surgery, no difference was observed in the lung volumes and inspiratory
      muscular activation during the lung expansion technique (P > .05). The PPC
      incidence was higher in the deep breathing group (P < .05). Higher American
      Society of Anesthesiologists scores and surgery duration were the only predictors
      of PPC (n = 14, 11.2%). CONCLUSIONS: LETs do not modify the changes on
      thoracoabdominal mechanics or prevent PPCs after abdominal surgery. The
      indiscriminate use of LETs should not be routinely prescribed to prevent PPCs;
      however, more studies are required to confirm our results and to change the
      standard practice. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01993602; URL:
      www.clinicaltrials.gov.

PMID- 25973672
TI  - A Method for Determining Taxonomical Contributions to Group Differences in
      Microbiomic Investigations.
AB  - Here we show how one can decompose the contribution of different levels of
      taxonomic classification in terms of their impact on differences in the
      microbiota when comparing two groups. First we demonstrate a difficulty in trying
      to estimate taxonomic effects at multiple levels simultaneously and demonstrate
      an approach to determining which taxa have differences in means that are
      identified. We then develop a model based on an approach that is popular in the
      RNA-Seq analysis literature and apply it to the problem of determining which taxa
      differ between two patient groups. This model provides a more powerful method
      than simpler alternatives. A Bayesian computational strategy is used to obtain
      exact inference. Simulation studies indicate that the procedure works as
      intended, and an application to the study of COPD demonstrates the method's
      practical utility. Software is provided for implementing the method. 

PMID- 25973673
TI  - Structure and reactivity of boron-ate complexes derived from primary and
      secondary boronic esters.
AB  - Boron-ate complexes derived from primary and secondary boronic esters and
      aryllithiums have been isolated, and the kinetics of their reactions with
      carbenium ions studied. The second-order rate constants have been used to derive
      nucleophilicity parameters for the boron-ate complexes, revealing that
      nucleophilicity increased with (i) electron-donating aromatics on boron, (ii)
      neopentyl glycol over pinacol boronic esters, and (iii) 12-crown-4 ether. 

PMID- 25973674
TI  - Heavy atom quenched coumarin probes for sensitive and selective detection of
      biothiols in living cells.
AB  - A series of turn-on fluorescent probes with halogen acetyl amide at the 3
      position of coumarin derivatives were synthesized. Fluorescence of these probes
      was efficiently quenched by heavy halogen atoms (Br and I, not Cl), which could
      be successfully used for selective detection of biothiols with the sensitivity of
      Cys > GSH > Hcy and much higher than thiol containing proteins. These represent
      the smallest fluorescence quenchers in designing fluorescent probes for detecting
      both endogenous and exogenous biothiols in living cells. 

PMID- 25973675
TI  - Breastfeeding initiation among macrosomic infants born to obese nondiabetic
      mothers.
AB  - BACKGROUND: Women who are overweight or obese are at risk for maternal and
      neonatal medical complications, including macrosomia (birth weight >=4,000 g),
      that may contribute to breastfeeding initiation failure. This study examined
      factors associated with breastfeeding initiation among obese women without
      diabetes who delivered macrosomic infants. STUDY DESIGN AND METHODS: A
      retrospective chart review was conducted from 2008 to 2011. Based on prepregnancy
      body mass index (in kg/m(2)), women were classified as normal (18-24.9),
      overweight (25-29.9), obese (30-34.9), very obese (35-39.9), and extremely obese
      (>=40). Intention to breastfeed was ascertained prenatally, and breastfeeding
      initiation was defined if at discharge >=50% of the infant feedings were
      breastmilk. RESULTS: Twenty-nine percent of the population was overweight, 23%
      obese, 14% very obese, and 12% extremely obese. Intention to breastfeed was
      similar among normal-weight, overweight, obese, and very obese women but was
      significantly lower for those who were extremely obese (p<0.05). Breastfeeding
      initiation was 75% for normal-weight, 72% for overweight, 71% for obese, 66% for
      very obese, and 53% for extremely obese women (p<0.05). Among women who intended
      to breastfeed, breastfeeding initiation was uniformly high: 94% for normal
      weight, 93% for overweight, 95% for obese, 92% for very obese, and 87% for
      extremely obese women. CONCLUSIONS: Intention to breastfeed as well as
      breastfeeding initiation was significantly lower for extremely obese women. Lack
      of intention to breastfeed declared during the antepartum period by extremely
      obese women highlights a need as well as an opportunity for intervention.

PMID- 25973676
TI  - Decoding the timing and target locations of saccadic eye movements from neuronal
      activity in macaque oculomotor areas.
AB  - OBJECTIVE: The control of movement timing has been a significant challenge for
      brain-machine interfaces (BMIs). As a first step toward developing a timing-based
      BMI, we aimed to decode movement timing and target locations in a visually guided
      saccadic eye movement task using the activity of neurons in the primate frontal
      eye field (FEF) and supplementary eye field (SEF). APPROACH: For this purpose, we
      developed a template-matching method that could recruit a variety of neurons in
      these areas. MAIN RESULTS: As a result, we were able to achieve a favorable
      estimation of saccade onset: for example, data from 20 randomly sampled FEF
      neurons or 40 SEF neurons achieved a median estimation error of ~10 ms with an
      interquartile range less than 50 ms (+/- ~25 ms). In the best case, seven
      simultaneously recorded SEF neurons using a multi-electrode array achieved a
      comparable accuracy (10 +/- 30 ms). The method was significantly better than a
      heuristic method that used only a group of movement cells with sharp discharges
      at the onset of saccades. The estimation of target location was less accurate but
      still favorable, especially when we estimated target location at a timing of 200
      ms after the onset of saccade: the method was able to discriminate 16 targets
      with an accuracy of 90%, which differed not only in their directions (eight
      directions) but also in amplitude (10/20 degrees ) when we used data from 61
      randomly sampled FEF neurons. SIGNIFICANCE: The results show that the timing,
      amplitude and direction of saccades can be decoded from neuronal activity in the
      FEF and SEF and further suggest that timing-based BMIs can be developed by
      decoding timing information using the template-matching method.

PMID- 25973677
TI  - Powerful Surface Chemistry Approach for the Grafting of Alkyl Multilayers on
      Aluminum Nanoparticles.
AB  - The synthesis of aluminum nanoparticles (Alnp) has raised promising perspectives
      these past few years for applications in energetic materials. However, because of
      their high reactivity, it is crucial to functionalize them before their use. In
      this work, we propose an original and simple chemical approach to graft
      spontaneously alkyl layers derived from alkyl halides at the surface of Alnp, by
      relying on the highly reductive character of these nanoparticles, when they are
      in the unoxidized form. Alnp were prepared in a glovebox and reacted with alkyl
      halides (RI and RBr) to give modified Alnp-R, as shown by infrared spectroscopy
      (IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction,
      thermogravimetric analysis (TGA), and microscopy. The coating is made of alkyl
      multilayers, which were found to be strongly anchored at the Alnp surface, as it
      resisted 2 h of rinsing in toluene. An electrocatalytic electron transfer
      promoted by Alnp is proposed to describe the mechanism of this grafting reaction.

PMID- 25973678
TI  - Tolerability of a Skin Care Regimen Formulated for Acne-Prone Skin in Children.
AB  - BACKGROUND: The epidemiology and demographic profile of acne vulgaris has evolved
      over the past several decades, with a noted earlier onset occurring in patients
      as young as 7 years of age. The combination of a foaming facial wash and a facial
      moisturizer with a sun protection factor (SPF) of 30 is an over-the-counter
      cleansing and moisturizing regimen for acne-prone skin that has been shown to be
      safe and tolerable in subjects 12 years of age and older. OBJECTIVES: To assess
      the tolerability of this skin care regimen in children ages 7 to 11 years with
      acne-prone skin. METHODS: This was an open-label, single-center study that
      investigated the safety and tolerability of these products in subjects 7 to 11
      years of age (ClinicalTrials.gov, NCT01909713). Subjects used the foaming wash
      twice daily and the SPF 30 moisturizer once daily. Subjects were assessed for
      cutaneous tolerability, and satisfaction at baseline and weeks 1 and 3. RESULTS:
      Thirty-five subjects enrolled and completed the study. The cutaneous tolerability
      score of most subjects was none when assessed by the investigator and subject or
      legally authorized representative at weeks 1 and 3. The products were well
      tolerated and a positive impression for cosmetic acceptability was reported for
      both products by the study population on the questionnaire. CONCLUSIONS: This
      study supports the use of a skin care regimen comprising a wash and a moisturizer
      in acne-prone patients as young as 7 years old since these products were safe,
      well tolerated, and liked by subjects.

PMID- 25973679
TI  - Targeted Metabolomic Analysis of Head and Neck Cancer Cells Using High
      Performance Ion Chromatography Coupled with a Q Exactive HF Mass Spectrometer.
AB  - In this study, we have demonstrated a targeted metabolomics method for analysis
      of cancer cells, based on high-performance ion chromatography (IC) separation, Q
      Exactive HF MS for high-resolution and accurate-mass (HR/AM) measurement and the
      use of stable isotope-labeled internal standards for absolute quantitation. Our
      method offers great technical advantages for metabolite analysis, including
      exquisite sensitivity, high speed and reproducibility, and wide dynamic range.
      The high-performance IC provided fast separation of cellular metabolites within
      20 min and excellent resolving power for polar molecules including many isobaric
      metabolites. The IC/Q Exactive HF MS achieved wide dynamic ranges of 5 orders of
      magnitude for six targeted metabolites, pyruvate, succinic acid, malic acid,
      citric acid, fumaric acid, and alpha-ketoglutaric acid, with R(2) ~ 0.99. Using
      this platform, metabolites can be simultaneously quantified from low fmol/MUL to
      nmol/MUL levels in cellular samples. The high flow rate IC at 380 MUL/min has
      shown excellent reproducibility for a large set of samples (150 injections), with
      minimal variations of retention time (SD < +/- 0.03 min). In addition, the IC-MS
      based approach acquires targeted and global metabolomic data in a same analytical
      run, and the use of stable isotope-labeled standards facilitates accurate
      quantitation of targeted metabolites in large-scale metabolomics analysis. This
      metabolomics approach has been successfully applied to analysis of targeted
      metabolites in head and neck cancer cells as well as cancer stem-like cells
      (CSCs), and the findings indicate that the metabolic phenotypes may be distinct
      between high and low invasive head and neck cancer cells and between CSCs and non
      SCCs. 

PMID- 25973680
TI  - RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR
      negative bladder cancer-initiating cells.
AB  - Cancer-initiating cell (CIC) is critical in cancer development, maintenance and
      recurrence. The reverse expression pattern of coxsackie and adenovirus receptor
      (CAR) and alphanu integrin in bladder cancer decreases the infection efficiency
      of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus,
      carrying EGFP or TNF-related apoptosis-inducing ligand (TRAIL) gene (Onco(Ad).RGD
      hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and
      cancer-initiating T24 sphere cells. Onco(Ad).RGD-hTERT-EGFP had enhanced
      infection ability and cytotoxic effect on T24 cells and T24 sphere cells, but
      little cytoxicity on normal urothelial SV-HUC-1 cells compared with the
      unmodified virus Onco(Ad).hTERT-EGFP. Notably, Onco(Ad).RGD-hTERT-TRAIL induced
      apoptosis in T24 cells and T24 sphere cells. Furthermore, it completely inhibited
      xenograft initiation established by the oncolytic adenovirus-pretreated T24
      sphere cells, and significantly suppressed tumor growth by intratumoral
      injection. These results provided a promising therapeutic strategy for CAR
      negative bladder cancer through targeting CICs. 

PMID- 25973681
TI  - Modulation of radiochemoimmunotherapy-induced B16 melanoma cell death by the pan
      caspase inhibitor zVAD-fmk induces anti-tumor immunity in a HMGB1-, nucleotide-
      and T-cell-dependent manner.
AB  - One prerequisite that radiotherapy (RT) and chemotherapy (CT) result in anti
      tumor immune responses is triggering of immunogenic cell death forms such as
      necroptosis. The latter is inducible by inhibition of apoptosis with the pan
      caspase inhibitor zVAD-fmk. The design of multimodal therapies that overcome
      melanoma's resistance to apoptosis is a big challenge of oncoimmunology. As hints
      exist that immune stimulation by hyperthermia (HT) augments the efficacy of
      melanoma therapies and that tumors can be sensitized for RT with zVAD-fmk, we
      asked whether combinations of RT with dacarbazine (DTIC) and/or HT induce
      immunogenic melanoma cell death and how this is especially influenced by zVAD
      fmk. Necroptosis was inducible in poorly immunogenic B16-F10 melanoma cells and
      zVAD-fmk generally increased melanoma cell necrosis concomitantly with the
      release of HMGB1. Supernatants (SNs) of melanoma cells whose cell death was
      modulated with zVAD-fmk induced an upregulation of the activation markers CD86
      and MHCII on macrophages. The same was seen on dendritic cells (DCs), but only
      when zVAD-fmk was added to multimodal tumor treatments including DTIC. DCs of
      MyD88 KO mice and DCs incubated with SNs containing apyrase did not increase the
      expression of these activation markers on their surface. The in vivo experiments
      revealed that zVAD-fmk decreases the tumor growth significantly and results in a
      significantly reduced tumor infiltration of Tregs when added to multimodal
      treatment of the tumor with RT, DTIC and HT. Further, a significantly increased
      DC and CD8+ T-cell infiltration into the tumor and in the draining lymph nodes
      was induced, as well as an increased expression of IFNgamma by CD8+ T cells.
      However, zVAD-fmk did not further reduce tumor growth in MyD88 KO mice, mice
      treated with apyrase or RAG KO mice. We conclude that HMGB1, nucleotides and CD8+
      T cells mediate zVAD-fmk induced anti-melanoma immune reactions in multimodal
      therapy settings. 

PMID- 25973682
TI  - Stressing out the ER in aminoglycoside-induced hearing loss.

PMID- 25973684
TI  - Oblongifolin C inhibits metastasis by up-regulating keratin 18 and tubulins.
AB  - Tumor metastasis is the main cause of cancer-related patient death. In this
      study, we performed a wound healing migration screen to search for a metastatic
      inhibitor within our library of natural compounds. We found that oblongifolin C
      (OC), a natural compound extracted from Garcinia yunnanensis Hu, is an effective
      inhibitor of metastasis in human esophageal squamous carcinoma Eca109 cells. The
      transwell migration and matrigel invasion assay results also showed that OC
      inhibits the migration of Eca109 cells and HepG2 cells. OC can increase the
      expression of tubulin, indicating that OC inhibits metastasis via tubulin
      aggregation. In addition, the Western blotting, real-time PCR, and immunostaining
      results indicated that OC increases the expression of keratin18. Furthermore, the
      knockdown of keratin 18 by small interfering RNAs inhibited the expression of
      tubulin and increased the metastasis of cancer cells, suggesting that keratin 18
      is the upstream signal of tubulin and plays a vital role in metastasis. A
      subsequent study in a tail vein injection metastasis model showed that OC can
      significantly inhibit pulmonary metastasis, as revealed by immunohistochemistry
      staining. Taken together, our results suggest that OC inhibits metastasis through
      the induction of the expression of keratin 18 and may be useful in cancer
      therapy. 

PMID- 25973683
TI  - XBP1 mitigates aminoglycoside-induced endoplasmic reticulum stress and neuronal
      cell death.
AB  - Here we study links between aminoglycoside-induced mistranslation, protein
      misfolding and neuropathy. We demonstrate that aminoglycosides induce misreading
      in mammalian cells and assess endoplasmic reticulum (ER) stress and unfolded
      protein response (UPR) pathways. Genome-wide transcriptome and proteome analyses
      revealed upregulation of genes related to protein folding and degradation.
      Quantitative PCR confirmed induction of UPR markers including C/EBP homologous
      protein, glucose-regulated protein 94, binding immunoglobulin protein and X-box
      binding protein-1 (XBP1) mRNA splicing, which is crucial for UPR activation. We
      studied the effect of a compromised UPR on aminoglycoside ototoxicity in
      haploinsufficient XBP1 (XBP1(+/-)) mice. Intra-tympanic aminoglycoside treatment
      caused high-frequency hearing loss in XBP1(+/-) mice but not in wild-type
      littermates. Densities of spiral ganglion cells and synaptic ribbons were
      decreased in gentamicin-treated XBP1(+/-) mice, while sensory cells were
      preserved. Co-injection of the chemical chaperone tauroursodeoxycholic acid
      attenuated hearing loss. These results suggest that aminoglycoside-induced ER
      stress and cell death in spiral ganglion neurons is mitigated by XBP1, masking
      aminoglycoside neurotoxicity at the organismal level. 

PMID- 25973686
TI  - Fat/carbohydrate ratio but not energy density determines snack food intake and
      activates brain reward areas.
AB  - The snack food potato chips induces food intake in ad libitum fed rats, which is
      associated with modulation of the brain reward system and other circuits. Here,
      we show that food intake in satiated rats is triggered by an optimal
      fat/carbohydrate ratio. Like potato chips, an isocaloric fat/carbohydrate mixture
      influenced whole brain activity pattern of rats, affecting circuits related e.g.
      to reward/addiction, but the number of modulated areas and the extent of
      modulation was lower compared to the snack food itself. 

PMID- 25973685
TI  - Impact of spatial dispersion, evolution, and selection on Ebola Zaire Virus
      epidemic waves.
AB  - Ebola virus Zaire (EBOV) has reemerged in Africa, emphasizing the global
      importance of this pathogen. Amidst the response to the current epidemic, several
      gaps in our knowledge of EBOV evolution are evident. Specifically, uncertainty
      has been raised regarding the potential emergence of more virulent viral variants
      through amino acid substitutions. Glycoprotein (GP), an essential component of
      the EBOV genome, is highly variable and a potential site for the occurrence of
      advantageous mutations. For this study, we reconstructed the evolutionary history
      of EBOV by analyzing 65 GP sequences from humans and great apes over diverse
      locations across epidemic waves between 1976 and 2014. We show that, although
      patterns of spatial dispersion throughout Africa varied, the evolution of the
      virus has largely been characterized by neutral genetic drift. Therefore, the
      radical emergence of more transmissible variants is unlikely, a positive finding,
      which is increasingly important on the verge of vaccine deployment. 

PMID- 25973687
TI  - Rosiglitazone improves learning and memory ability in rats with type 2 diabetes
      through the insulin signaling pathway.
AB  - Diabetes mellitus (DM) is associated with moderate cognitive deficits and
      neurophysiologic and structural changes in the brain, a condition that is
      referred to as diabetic encephalopathy. This study was performed to investigate
      the effect of rosiglitazone (RSG) on learning and memory in rats with DM and
      elucidate possible mechanisms underlying this condition. Thirty-two male Sprague
      Dawley rats were randomly divided into 4 groups: control (C, n = 8), DM (n = 8),
      RSG-administered control (C + RSG, n = 8) and RSG-administered DM groups (DM +
      RSG, n = 8). At 8 weeks after drug administration, Morris water maze was used to
      perform a training and probe trial to detect spatial learning and memory
      abilities. Western blot and immunohistochemistry were also used to detect changes
      in proteins involved in the insulin signal transduction pathway, such as the
      insulin receptor, insulin receptor substrate-1, protein kinase B, phosphorylated
      cAMP response element-binding protein and B-cell lymphoma 2, in the hippocampus
      of the rats. This study found that RSG could normalize the impaired insulin
      signal transduction in type 2 DM. The authors showed that RSG modulated the
      central insulin signaling axis. 

PMID- 25973688
TI  - Growth approaches to academic development: Research into academic trajectories
      and growth assessment, goals, and mindsets.

PMID- 25973689
TI  - Growth.

PMID- 25973690
TI  - Applying molecular epidemiology in pediatric leukemia.
AB  - Molecular epidemiology is the study of genetic and environmental risk for
      disease, with much effort centered on cancer. Childhood leukemia occurs in nearly
      a third of all patients newly diagnosed with pediatric cancer. only a small
      percentage of these new cases of childhood leukemia are associated with high
      penetrant hereditary cancer syndromes. Childhood leukemia, especially acute
      lymphoblastic leukemia, has been associated with a dysregulated immune system due
      to delayed infectious exposure at a young age. Identical twins with childhood
      leukemia suggest that acute lymphoblastic leukemia begins in utero and that the
      concordant presentation is due to a shared preleukemia subclone via placental
      transfer. Investigation of single nucleotide polymorphisms within candidate genes
      find that leukemia risk may be attributed to population-based polymorphisms
      affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B
      cell development. More recently, genome-wide association studies for leukemia
      risk has led investigators to genes associated with B-cell development. When
      describing leukemia predisposition due to hereditary cancer syndromes, the
      following 6 categories become apparent on the basis of biology and clinical
      presentation: (1) genetic instability/DNA repair syndromes, (2) cell
      cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere
      maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription
      factor syndromes and pure familial leukemia. understanding the molecular
      epidemiology of childhood leukemia can affect the treatment and tumor
      surveillance strategies for these high risk patients and their family members. 

PMID- 25973691
TI  - The role of T regulatory cells in immunopathogenesis of myasthenia gravis:
      implications for therapeutics.
AB  - T regulatory cells (Tregs) are crucial for the development of self-tolerance and
      are the major focus in many studies interpreting the pathogenesis of myasthenia
      gravis (MG), an autoimmune-based disease. In normal conditions, Tregs regulate
      the immune responses, while impaired regulatory function of these cells can lead
      to autoimmunity. Recent studies have confirmed that the thymic and peripheral
      blood CD4(+)CD25(+) Tregs of MG are defective in functions and/or in numbers,
      which are associated with disease severity; approaches to correct the defects of
      these Tregs may be promising in the treatment of MG. This review discusses recent
      studies on characteristics, quantitative and qualitative changes of Tregs and
      possible mechanisms that are involved in the impairment of these cells in MG
      pathogenesis. In addition, new approaches inducing Treg generation that are
      currently being investigated as therapies for MG, will be discussed as well as
      proposed approaches for future therapies. 

PMID- 25973692
TI  - Satisfaction With Cochlear Implants in Postlingually Deaf Adults and Its
      Nonaudiological Predictors: Psychological Distress, Coping Strategies, and Self
      Esteem.
AB  - OBJECTIVE: A postlingually deaf patient who receives a cochlear implant (CI)
      acquires multiple benefits, not just audiological but also nonaudiological:
      improvement in quality of life, psychological well-being, and social interaction.
      The aim of the study was to ascertain the relationship between the CI
      satisfaction experienced by adult, postlingually deaf individuals and their level
      of psychological distress, stress coping strategies, and global self-esteem. We
      also considered sociodemographic variables (such as sex, age, education,
      marital/partner status, and employment/study status), variables related to their
      deafness, and their length of experience with a CI. DESIGN: The study had a cross
      sectional design in which participants were asked to fill in a mailed personal
      inquiry form seeking sociodemographic data and one question related to CI
      satisfaction, and the following questionnaires: General Health Questionnaire-28,
      the Brief Coping Orientation to Problems Experienced, and the Rosenberg Self
      Esteem Scale. This study included 98 patients with postlingual deafness between
      19 and 85 years old who had unilateral CIs. For some analyses, the patients were
      also divided into two groups: younger (<=60 years) and older (>60 years). Two
      other subgroups were those with shorter CI experience (1 to 2 years) and those
      with longer CI experience (5 to 6 years). As an objective reference, speech
      perception scores in quiet and in noise were also used. RESULTS: The majority of
      postlingually deaf subjects rated their CI satisfaction as high or very high, and
      this was at similar levels in younger and older subjects, as well as in those who
      had used CIs for either a short or a long time. CI satisfaction was not related
      to speech perception scores, duration of deafness, length of CI use, or other
      sociodemographic factors. Positive self-esteem, having less severe symptoms of
      depression, and the use of humor or self-distraction were conducive to CI
      satisfaction. Using a coping strategy of denial had a negative association with
      CI satisfaction. Coping strategies and symptoms of mental distress varied between
      younger and older subjects. For younger subjects, higher CI satisfaction was
      associated with lower severity of depressive symptoms, whereas for the elderly,
      higher CI satisfaction was associated with less severe social dysfunction
      symptoms. Over the years of using a CI, the same strategy may have a different
      psychological function in providing satisfaction: for example, venting, which in
      the group with a short CI experience is negatively correlated to satisfaction, is
      positively correlated to satisfaction for those with longer CI experience.
      CONCLUSIONS: The results show that psychological factors-self-esteem, distress,
      and coping strategies-are important for CI satisfaction in postlingually deaf CI
      users. The results point to advantages in widening the availability of various
      tailored forms of psychological intervention for patients with postlingual
      deafness after receiving a CI.

PMID- 25973693
TI  - 18F-FDG PET-CT: predicting recurrence in patients following percutaneous
      cryoablation treatment for stage I primary non-small-cell lung cancer.
AB  - PURPOSE: The aim of this study was to understand the imaging features of fluorine
      18 fluorodeoxyglucose ((18)F-FDG) PET-computed tomography (CT) in
      postcryoablation lung cancer patients that could help predict recurrence.
      METHODS: We identified 28 patients with 30 lesions treated by means of
      percutaneous cryoablation for stage I non-small-cell lung cancer. Two experienced
      nuclear radiologists blindly reviewed baseline images and follow-up (18)F-FDG PET
      CT scans for a minimum of 24 months, with discrepancy in interpretation resolved
      by consensus. Nineteen lesions had undergone baseline PET-CT studies, whereas 11
      lesions had undergone only baseline CT studies. Follow-up PET-CT studies were
      analyzed for up to 24 months, whereas the recurrence-free survival analysis was
      performed for 36 months. RESULTS: The average maximum standardized uptake value
      (SUV(max)) at baseline (n = 19) was 5.2 +/- 3.9 and the average CT area at
      baseline was 2.2 +/- 1.6 cm(2). Only the CT area was significantly different
      between recurring and nonrecurring lesions at baseline (P = 0.0028). The Kaplan
      Meier survival analysis showed that dichotomizing lesions around 2 cm on CT did
      not result in a statistically significant survival difference (hazard ratio =
      1.42, 95% confidence interval: 0.63-2.21). The average SUV(max) at first follow
      up was 1.9 +/- 1.8 for 27 lesions, whereas the average SUV(max) of recurrent
      lesions was 2.2 +/- 2.2 and that of nonrecurrent lesions was 1.5 +/- 0.3 (P =
      0.17). Six lesions had SUV(max) more than or equal to 2.5 within 24 months, all
      of which recurred in the ablation zone. CONCLUSION: (18)F-FDG PET-CT is a
      valuable tool for determining treatment response and for distinguishing benign
      from malignant lesions after cryoablation. The CT area was most predictive of
      future recurrence at baseline, whereas SUV(max) more than or equal to 2.5 was
      most predictive of future recurrence at first follow-up.

PMID- 25973695
TI  - Citrus tristeza virus: making an ally from an enemy.
AB  - Virus diseases of perennial trees and vines have characteristics not amenable to
      study using small model annual plants. Unique disease symptoms such as graft
      incompatibilities and stem pitting cause considerable crop losses. Also, viruses
      in these long-living plants tend to accumulate complex populations of viruses and
      strains. Considerable progress has been made in understanding the biology and
      genetics of Citrus tristeza virus (CTV) and in developing it into a tool for crop
      protection and improvement. The diseases in tree and vine crops have
      commonalities for which CTV can be used to develop a baseline. The purpose of
      this review is to provide a necessary background of systems and reagents
      developed for CTV that can be used for continued progress in this area and to
      point out the value of the CTV-citrus system in answering important questions on
      plant-virus interactions and developing new methods for controlling plant
      diseases. 

PMID- 25973694
TI  - Ex-vivo biodistribution and micro-PET/CT imaging of 18F-FDG, 18F-FLT, 18F-FMISO,
      and 18F-AlF-NOTA-PRGD2 in a prostate tumor-bearing nude mouse model.
AB  - OBJECTIVE: (18)F-Fluorodeoxyglucose ((18)F-FDG), (18)F-fluoro-3'-deoxy-3'-L
      fluorothymidine ((18)F-FLT), (18)F-fluoromisonidazole ((18)F-FMISO), and (18)F
      AlF-NOTA-PRGD2 ((18)F-RGD) are all commonly used PET tracers for tumor diagnosis
      based on different mechanisms of tissue uptake. This study compared the ex-vivo
      biodistribution and PET/computed tomography (CT) imaging studies of these four
      PET tracers in a xenograft prostate tumor-bearing mouse model. MATERIALS AND
      METHODS: Nude mice were inoculated with 5 * 10 PC-3 cells in the right armpit.
      The ex-vivo biodistribution of (18)F-FDG, (18)F-FLT, (18)F-FMISO, and (18)F-RGD
      at 30, 60, 90, and 120 min after injection was compared. Micro-PET/CT images of
      (18)F-FDG, (18)F-FLT, and (18)F-RGD were acquired at 60 min, whereas (18)F-FMISO
      images were acquired at 90 min after injection. RESULTS: The tumors were clearly
      visualized by micro-PET/CT using all four PET tracers. Ex-vivo biodistribution
      results showed highest tumor accumulation and tumor-to-muscle ratio of (18)F-FDG
      at each time point, accompanied by physiologically high uptakes in the brain,
      heart, and intestinal tract. Modest uptake of (18)F-FLT and (18)F-FMISO in tumors
      was observed at 60 and 90 min after injection, with less interference from other
      tissues compared with (18)F-FDG. Besides, (18)F-RGD also exhibited high tumor
      specificity; however, relatively low uptake was observed in the tumor.
      CONCLUSION: Our results demonstrated the potential of (18)F-FMISO and (18)F-FLT
      in the diagnosis of xenograft prostate cancer.

PMID- 25973696
TI  - Pre-transplant angiotensin receptor II type 1 antibodies and risk of post
      transplant focal segmental glomerulosclerosis recurrence.
AB  - Post-kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is
      a major problem. AT1R is expressed on podocyte; its expression is elevated in the
      proteinuric state. Using an ELISA, we tested pre-transplant sera of 28 patients
      with history of idiopathic FSGS for anti-AT1R levels and serum soluble urokinase
      type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence
      of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as
      controls. Twelve patients had biopsy proven post-transplant FSGS recurrence at
      1.5 months. No difference was found in the pre-transplant suPAR levels of FSGS
      patients (5993 +/- 2292 pg/mL) vs. PKD (7334 +/- 4538 pg/mL) (p = 0.23). Serum
      suPAR levels in patients with FSGS recurrence (5786 +/- 1899 pg/mL) vs. no FSGS
      recurrence (6149 +/- 2598 pg/mL) (p = 0.69) were not different. Anti-AT1R levels
      in patients with FSGS were 12.66 +/- 11.85 U/mL vs. 8.69 +/- 6.52 U/mL in PKD (p
      = 0.32); however, a difference was found in patients with and without FSGS
      recurrence 20.41 +/- 14.36 U/mL 6.84 +/- 4.181 U/mL, respectively (p < 0.01).
      Area under curve for suPAR and anti-AT1R to predict post-transplant FSGS
      recurrence was 0.51 and 0.84, respectively. Pre-transplant anti-AT1R levels
      appear to be a helpful biomarker in identifying patients at high risk of post
      transplant FSGS recurrence.

PMID- 25973698
TI  - Reaction CH3 + CH3 -> C2H6 Studied over the 292-714 K Temperature and 1-100 bar
      Pressure Ranges.
AB  - Reaction of recombination of methyl radicals, CH3 + CH3 -> C2H6 (1) was studied
      using pulsed laser photolysis coupled to transient UV-vis absorption spectroscopy
      over the 292-714 K temperature and 1-100 bar pressure ranges (bath gas He), very
      close to the high-pressure limit. Methyl radicals were produced by photolysis of
      acetone at 193.3 nm or in the reaction of electronically excited oxygen atoms
      O((1)D), produced in the photolysis of N2O at 193.3 nm, with CH4, and subsequent
      reaction of OH with CH4. Temporal profiles of CH3 were recorded via absorption at
      216.36 and 216.56 nm using a xenon arc lamp and a spectrograph. The absolute
      intensity of the photolysis light inside the reactor was determined by an
      accurate in situ actinometry based on the ozone formation in photolysis of
      N2O/O2/N2 mixtures. The rate constant of reaction 1 in the high-pressure limit
      has a negative temperature dependence: k1,inf = (5.66 +/- 0.43) * 10(-11)(T/298
      K)(-0.37) cm(3) molecule(-1) s(-1) (292-714 K). 

PMID- 25973697
TI  - The role of muscle proprioceptors in human limb position sense: a hypothesis.
AB  - In this mini-review I have proposed that there are two kinds of position sense,
      one a sense of the position of one part of the body relative to another, the
      other a sense of the location in space of our body and its limbs. A common method
      used to measure position sense is to ask subjects to match with one arm the
      position adopted by the other. Here all of the evidence points to muscle spindles
      as the major proprioceptors, with cutaneous receptors acting as proprioceptors
      providing a supporting role. Other senses such as vision do not play a major
      role. The sense of localisation in space measured by pointing to the arm, rather
      than matching its position, I propose, is not served by proprioceptors but by
      exteroceptors, vision, touch and hearing. Here the afferent input is relayed to
      sensory areas of the brain, to address the postural schema, a cortical map of the
      body and limbs, specifying its size and shape. It is here that spatial location
      is computed. This novel interpretation of position sense as two separate entities
      has the advantage of proposing new, future experiments and if it is supported by
      the findings, it will represent an important step forward in our understanding of
      the central processing of spatial information. 

PMID- 25973699
TI  - Are medical students being taught anatomy in a way that best prepares them to be
      a physician?
AB  - Reasoning in a clinical context is an attribute of medical expertise. Clinical
      reasoning in medical school can be encouraged by teaching basic science with a
      clinical emphasis. The aim of this study was to investigate whether anatomy is
      being taught in a way that facilitates the development of clinical reasoning. Two
      multiple-choice tests on thoracic anatomy were developed using a modified Delphi
      approach with groups of four clinical consultants and four teachers,
      respectively, expressing their opinions about knowledge relevant to thoracic
      anatomy. Validity was assessed by administering the tests to clinical
      consultants, anatomy teachers, and pre-course medical students. Post-course
      medical students took both tests to explore the focus of the course, i.e.,
      whether it facilitated clinical reasoning. The pre-course students scored
      significantly lower than the teachers and post-course students on both tests and
      lower than the consultants on the consultants' test (P < 0.001 for all
      comparisons). The teachers significantly outperformed the consultants (P = 0.03
      on the consultants' test, P < 0.001 on the teachers' test) and the medical
      students (P < 0.001 on both tests). The post-course students scored significantly
      lower on the consultants' test (P = 0.001) and significantly higher on the
      teachers' test (P = 0.02) than the consultants. This study demonstrates poor
      performances by medical students on a test containing clinically relevant
      anatomy, implying that the teaching they have received has not encouraged
      clinical reasoning.

PMID- 25973700
TI  - Endovascular therapy: the dawning of a new era.

PMID- 25973701
TI  - Veronica Murray MD, PhD, 1949-2014: Specialist in Internal Medicine and Senior
      Scientist, Karolinska Institutet, Danderyd Hospital, Stockholm.

PMID- 25973702
TI  - Is more physiotherapy better after stroke?
AB  - 'More is better' has been the mantra for physiotherapists working in stroke
      rehabilitation. Studies examining the neuroplasticity of the brain have shown
      that repetitive, meaningful practice is essential to drive positive plasticity,
      and meta-analyses of clinical trials provide evidence of benefit of increased
      therapy provision. However, a recent large clinical trial appears to contradict
      this evidence. The CIRCIT trial investigated two alternative models of
      physiotherapy service delivery for people after stroke. Despite participants in
      the circuit class therapy arm of the trial receiving an additional 22 h of
      physiotherapy time, their outcomes were not superior to usual care. This
      editorial interrogates and provides some possible explanations for these
      apparently contradictory findings. 

PMID- 25973703
TI  - Combination of intracerebral haemorrhage and familial hypercholesterolemia in the
      acute hospital setting--a challenge for statin treatment?
AB  - It is estimated that worldwide, around 35 million people have familial
      hypercholesterolemia (FH). Thus, patients affected by the combination of FH and
      acute intracerebral hemorrhage (ICH) are not exceptional and neurologists should
      be prepared to encounter them. Despite a recent finding of beneficial association
      between statin use during hospitalization and improved outcomes, the increased
      risk of recurrent ICH in the long term may make clinicians avoid statins in
      patients with a history of ICH. However, discontinuing statins in patients with
      FH worsens cardiovascular outcomes and even increases all-cause mortality.
      Accordingly, the continuing statin treatment in an FH patient with an acute ICH
      is advisable. 

PMID- 25973704
TI  - Cognitive performance following lacunar stroke in Spanish-speaking patients:
      results from the SPS3 trial.
AB  - BACKGROUND: Cognitive impairment is frequent in lacunar stroke patients. The
      prevalence and pattern among Spanish-speaking patients are unknown and have not
      been compared across regions or with English-speaking patients. AIMS: The aim of
      this study was to characterize cognitive impairment in Spanish-speaking patients
      and compare it with English-speaking patients. METHODS: The baseline
      neuropsychological test performance and the prevalence of mild cognitive
      impairment, defined as a z-score <= -1.5 on memory and/or non-memory tests, were
      evaluated in Spanish-speaking patients in the Secondary Prevention of Small
      Subcortical Strokes trial. RESULTS: Out of 3020 participants, 1177 were Spanish
      speaking patients residing in Latin America (n = 693), the United States (n =
      121), and Spain (n = 363). Low education (zero- to eight-years) was frequent in
      Spanish-speaking patients (49-57%). Latin American Spanish-speaking patients had
      frequent post-stroke upper extremity motor impairment (83%). Compared with
      English-speaking patients, all Spanish-speaking patient groups had smaller memory
      deficits and larger non-memory/motor deficits, with Latin American Spanish
      speaking patients showing the largest deficits median z-score -1.3 to -0.6 non
      memory tests; <=5.0 for Grooved Pegboard; -0.7 to -0.3 for memory tests). The
      prevalence of mild cognitive impairment was high and comparable with English
      speaking patients in the United States and Latin American Spanish-speaking
      patients but not the Spanish group: English-speaking patients = 47%, Latin
      American Spanish-speaking patients = 51%, US Spanish-speaking patients = 40%,
      Spanish Spanish-speaking patients = 29%, with >50% characterized as non-amnestic
      in Spanish-speaking patient groups. Older age [odds ratio per 10 years = 1.52,
      confidence interval = 1.35-1.71), lower education (odds ratio 0-4 years = 1.23,
      confidence interval = 0.90-1.67), being a Latin American resident (odds ratio =
      1.31, confidence interval = 0.87-1.98), and post-stroke disability (odds ratio
      Barthel Index <95 = 1.89, confidence interval = 1.43-2.50) were independently
      associated with mild cognitive impairment. CONCLUSIONS: Mild cognitive impairment
      in Secondary Prevention of Small Subcortical Strokes Spanish-speaking patients
      with recent lacunar stroke is highly prevalent but has a different pattern to
      that observed in English-speaking patients. A combination of socio-demographics,
      stroke biology, and stroke care may account for these differences.

PMID- 25973705
TI  - Elevated gamma-glutamyltransferase and erythrocyte sedimentation rate in ischemic
      stroke in discordant monozygotic twin study.

PMID- 25973706
TI  - Ethnicity and neuroimaging markers of cerebral small vessel disease: neglected
      but clinically important.

PMID- 25973707
TI  - Acute nephropathy after contrast agent administration for computed tomography
      perfusion and computed tomography angiography in patients with acute ischemic
      stroke.

PMID- 25973708
TI  - Implementation of clinical guidelines for secondary prevention of stroke.

PMID- 25973709
TI  - Ischemic stroke as unusual complication of sildenafil use.

PMID- 25973710
TI  - Factors associated with prehospital delay among stroke patients in a developing
      African country.

PMID- 25973711
TI  - Development of alien hand syndrome with degeneration of transcallosal fibers to
      the supplementary motor area: a case report.

PMID- 25973712
TI  - Impact of stroke after antithrombotics withdrawal on early neurological
      deterioration.

PMID- 25973713
TI  - Identification and functional characterization of soybean root hair microRNAs
      expressed in response to Bradyrhizobium japonicum infection.
AB  - Three soybean [Glycine max (L) Merr.] small RNA libraries were generated and
      sequenced using the Illumina platform to examine the role of miRNAs during
      soybean nodulation. The small RNA libraries were derived from root hairs
      inoculated with Bradyrhizobium japonicum (In_RH) or mock-inoculated with water
      (Un_RH), as well as from the comparable inoculated stripped root samples (i.e.
      inoculated roots with the root hairs removed). Sequencing of these libraries
      identified a total of 114 miRNAs, including 22 novel miRNAs. A comparison of
      miRNA abundance among the 114 miRNAs identified 66 miRNAs that were
      differentially expressed between root hairs and stripped roots, and 48 miRNAs
      that were differentially regulated in infected root hairs in response to B.
      japonicum when compared to uninfected root hairs (P <= 0.05). A parallel analysis
      of RNA ends (PARE) library was constructed and sequenced to reveal a total of 405
      soybean miRNA targets, with most predicted to encode transcription factors or
      proteins involved in protein modification, protein degradation and hormone
      pathways. The roles of gma-miR4416 and gma-miR2606b during nodulation were
      further analysed. Ectopic expression of these two miRNAs in soybean roots
      resulted in significant changes in nodule numbers. miRNA target information
      suggested that gma-miR2606b regulates a Mannosyl-oligosaccharide 1, 2-alpha
      mannosidase gene, while gma-miR4416 regulates the expression of a rhizobium
      induced peroxidase 1 (RIP1)-like peroxidase gene, GmRIP1, during nodulation.

PMID- 25973714
TI  - Profiling planktonic biomass using element-specific, multicomponent nuclear
      magnetic resonance spectroscopy.
AB  - Planktonic metabolism plays crucial roles in Earth's elemental cycles. Chemical
      speciation as well as elemental stoichiometry is important for advancing our
      understanding of planktonic roles in biogeochemical cycles. In this study, a
      multicomponent solid-state nuclear magnetic resonance (NMR) approach is proposed
      for chemical speciation of cellular components, using several advanced NMR
      techniques. Measurements by ssNMR were performed on (13)C and (15)N-labeled
      Euglena gracilis, a flagellated protist. 3D dipolar-assisted rotational
      resonance, double-cross-polarization (1)H-(13)C correlation spectroscopy, and
      (1)H-(13)C solid-state heteronuclear single quantum correlation spectroscopy
      successively allowed characterization of cellular components. These techniques
      were then applied to E. gracilis cultured in high and low ammonium media to
      demonstrate the power of this method for profiling and comparing cellular
      components. Cellular NMR spectra indicated that ammonium induced both paramylon
      degradation and amination. Arginine was stored as a nitrogen reserve and ammonium
      replaced by arginine catabolism via the arginine dihydrolase pathway. (15)N and
      (31)P cellular ssNMR indicated arginine and polyphosphate accumulation in E.
      gracilis, respectively. This chemical speciation technique will contribute to
      environmental research by providing detailed information on environmental
      chemical properties. 

PMID- 25973715
TI  - Absence of both Sos-1 and Sos-2 in peripheral CD4(+) T cells leads to PI3K
      pathway activation and defects in migration.
AB  - Sos-1 and Sos-2 are ubiquitously expressed Ras-guanine exchange factors involved
      in Erk-MAP kinase pathway activation. Using mice lacking genes encoding Sos-1 and
      Sos-2, we evaluated the role of these proteins in peripheral T-cell signaling and
      function. Our results confirmed that TCR-mediated Erk activation in peripheral
      CD4(+) T cells does not depend on Sos-1 and Sos-2, although IL-2-mediated Erk
      activation does. Unexpectedly, however, we show an increase in AKT
      phosphorylation in Sos-1/2dKO CD4(+) T cells upon TCR and IL-2 stimulation.
      Activation of AKT was likely a consequence of increased recruitment of PI3K to
      Grb2 upon TCR and/or IL-2 stimulation in Sos-1/2dKO CD4(+) T cells. The increased
      activity of the PI3K/AKT pathway led to downregulation of the surface receptor
      CD62L in Sos-1/2dKO T cells and a subsequent impairment in T-cell migration.

PMID- 25973717
TI  - Simulation Study of Hydrophobically Modified Chitosan as an Oil Dispersant
      Additive.
AB  - Hydrophobically modified chitosan (HMC) is being considered as a possible oil
      dispersant additive to reduce the volume of dispersant required in oil spill
      remediation. We present the results of discontinuous molecular dynamics (DMD)
      simulations intended to determine how the HMC architecture affects its ability to
      prevent oil aggregation. The HMCs have a comb copolymer architecture with
      hydrophobic side chains (modification chains) of various lengths (5-15 spheres)
      to represent alkane chains that are attached to the chitosan backbone. We
      calculated the oil's solvent accessible surface area (SASA), aggregate size
      distribution, and aggregate asymmetry at various values of the HMC modification
      chain length, modification density, and concentration to determine HMC efficacy.
      HMCs with long modification chains result in larger oil SASA than HMCs with short
      modification chains. For long modification chains, there is no increase in oil
      SASA with increasing modification density above a saturation value. The size
      distribution of the oil aggregates depends on the modification chain length;
      systems with long modification chains lead to large aspherical aggregates, while
      systems with short modification chains lead to small tightly packed aggregates. A
      parametric analysis reveals that the most important factor in determining the
      ability of HMCs to prevent oil aggregation is the interaction between the HMC's
      modification chains and the oil molecules, even when using short modification
      chains. We conclude that HMCs with long modification chains are likely to be more
      effective at preventing oil aggregation than HMCs with short modification chains,
      and that long modification chains impede spherical oil droplet formation. 

PMID- 25973716
TI  - Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed
      treatment with lamivudine, adefovir, and entecavir.
AB  - BACKGROUND AND AIM: In the past decade, many chronic hepatitis B (CHB) patients
      have undergone sequential treatment with lamivudine (LAM), adefovir (ADV), and
      entecavir (ETV) to manage antiviral resistance or insufficient suppression of HBV
      DNA. Very limited data are available on the efficacy of tenofovir (TDF) rescue
      regimens in patients with multidrug resistance (MDR). METHODS: We investigated
      the antiviral efficacy of TDF/LAM combination therapy versus TDF/ETV combination
      therapy in 52 patients who failed three previous antiviral therapies. RESULTS:
      The study subjects were treated with TDF/LAM combination therapy (n = 25) or
      TDF/ETV combination therapy (n = 27) for more than six months. Virologic response
      (VR) occurred in 39 (75%) patients (19 patients belonged to the TDF/LAM group and
      20 patients belonged to the TDF/ETV group). The VR rates were not different
      between the TDF/LAM and TDF/ETV groups (56.0% vs 51.9% at month 12, and 72.0% vs
      78.8% at month 18; log rank P = 0.515). In addition, treatment efficacy of
      TDF/LAM combination or TDF/ETV combination was not statistically different
      according to types of MDR. In multivariate analysis, absolute HBV-DNA level at
      the start of TDF rescue treatment (P < 0.001; OR, 0.452; 95% CI, 0.306-0.666) was
      only significantly associated with VR. CONCLUSIONS: TDF/ETV combination therapy
      was not associated with higher rate of VR compared with TDF/LAM combination
      therapy in MDR CHB patients. These results raise the suspicion about the
      superiority of the combination therapy over TDF monotherapy. The lower HBV-DNA
      levels at the start of TDF-based rescue therapy were associated with higher VR.

PMID- 25973718
TI  - Treatment of Adolescent Substance Use Disorders and Co-Occurring Internalizing
      Disorders: A Critical Review and Proposed Model.
AB  - BACKGROUND: The past several decades have seen dramatic growth in empirically
      supported treatments for adolescent substance use disorders (SUDs), yet even the
      most well-established approaches struggle to produce large or long-lasting
      improvements. These difficulties may stem, in part, from the high rates of
      comorbidity between SUDs and other psychiatric disorders. METHOD: We critically
      reviewed the treatment outcome literature for adolescents with co-occurring SUDs
      and internalizing disorders. RESULTS: Our review identified components of
      existing treatments that might be included in an integrated, evidence-based
      approach to the treatment of SUDs and internalizing disorders. An effective
      program may involve careful assessment, inclusion of parents or guardians, and
      tailoring of interventions via a modular strategy. CONCLUSIONS: The existing
      literature guides the development of a conceptual evidence-based, modular
      treatment model targeting adolescents with co-occurring internalizing and SUDs.
      With empirical study, such a model may better address treatment outcomes for both
      disorder types in adolescents.

PMID- 25973719
TI  - A comparative study on volatile metabolites profile of Dracaena cochinchinensis
      (Lour.) S.C. Chen xylem with and without resin using GC-MS.
AB  - Dragon's blood is a famous traditional Chinese medicine produced from source
      plants under bio- or abio-stress. Dracaena cochinchinensis (Lour.) S.C. Chen
      xylem (DX) is one of the most important sources of the medicine. In this work, a
      GC-MS method was developed for analysis of the n-hexane extracts of DX with resin
      (DXR) and without resin (DXW). The repeatability of the method was also
      investigated for a metabolite comparative study of the different xylems. About 80
      components were detected, 26 of which were identified in both DXR and DXN. Three
      sesquiterpenes (tau-cadinol, tau-muurolon and alpha-cadinol) were first
      discovered in Dracaena cochinchinensis (Lour.) S.C. Chen. The chromatographs of
      the two plant materials were compared and differences of compounds were found. It
      showed that phytosterols showed a dramatic rise in content, and sesquiterpenes
      were found to be synthesized in DXR.

PMID- 25973720
TI  - The coeliac stomach: gastritis in patients with coeliac disease.
AB  - BACKGROUND: Lymphocytic gastritis (LG) is an uncommon entity with varying
      symptoms and endoscopic appearances. This condition, as well as two forms of H.
      pylori-negative gastritis [chronic active gastritis (CAG) and chronic inactive
      gastritis (CIG)], appears to be more common in patients with coeliac disease (CD)
      based on single-centred studies. AIM: To compare the prevalence of LG, CAG and
      CIG among those with normal duodenal histology (or nonspecific duodenitis) and
      those with CD, as defined by villous atrophy (Marsh 3). METHODS: We analysed all
      concurrent gastric and duodenal biopsy specimens submitted to a national
      pathology laboratory during a 6-year period. We performed multiple logistic
      regression to identify independent predictors of each gastritis subtype. RESULTS:
      Among patients who underwent concurrent gastric and duodenal biopsy (n =
      287,503), the mean age was 52 and the majority (67%) were female. Compared to
      patients with normal duodenal histology, LG was more common in partial villous
      atrophy (OR: 37.66; 95% CI: 30.16-47.03), and subtotal/total villous atrophy (OR:
      78.57; 95% CI: 65.37-94.44). CD was also more common in CAG (OR for partial
      villous atrophy 1.93; 95% CI: 1.49-2.51, OR for subtotal/total villous atrophy
      2.42; 95% CI: 1.90-3.09) and was similarly associated with CIG (OR for partial
      villous atrophy 2.04; 95% CI: 1.76-2.35, OR for subtotal/total villous atrophy
      2.96; 95% CI: 2.60-3.38). CONCLUSIONS: Lymphocytic gastritis is strongly
      associated with coeliac disease, with increasing prevalence correlating with more
      advanced villous atrophy. Chronic active gastritis and chronic inactive gastritis
      are also significantly associated with coeliac disease. Future research should
      measure the natural history of these conditions after treatment with a gluten
      free diet.

PMID- 25973721
TI  - Landscape distribution of food and nesting sites affect larval diet and nest
      size, but not abundance of Osmia bicornis.
AB  - Habitat fragmentation is a major threat for beneficial organisms and the
      ecosystem services they provide. Multiple-habitat users such as wild bees depend
      on both nesting and foraging habitat. Thus, they may be affected by the
      fragmentation of at least two habitat types. We investigated the effects of
      landscape-scale amount of and patch isolation from both nesting habitat (woody
      plants) and foraging habitat (specific pollen sources) on the abundance and diet
      of Osmia bicornis L. Trap-nests of O. bicornis were studied in 30 agricultural
      landscapes of the Swiss Plateau. Nesting and foraging habitats were mapped in a
      radius of 500 m around the sites. Pollen composition of larval diet changed as
      isolation to the main pollen source, Ranunculus, increased, suggesting that O.
      bicornis adapted its foraging strategy in function of the nest proximity to main
      pollen sources. Abundance of O. bicornis was neither related to isolation or
      amount of nesting habitat nor to isolation or abundance of food plants.
      Surprisingly, nests of O. bicornis contained fewer larvae in sites at forest edge
      compared to isolated sites, possibly due to higher parasitism risk. This study
      indicates that O. bicornis can nest in a variety of situations by compensating
      scarcity of its main larval food by exploiting alternative food sources. 

PMID- 25973722
TI  - The role of conformational selection in the molecular recognition of the wild
      type and mutants XPA67-80 peptides by ERCC1.
AB  - Molecular recognition is a fundamental step in the coordination of biomolecular
      pathways. Understanding how recognition and binding occur between highly flexible
      protein domains is a complex task. The conformational selection theory provides
      an elegant rationalization of the recognition mechanism, especially valid in
      cases when unstructured protein regions are involved. The recognition of a poorly
      structured peptide, namely XPA67-80 , by its target receptor ERCC1, falls in this
      challenging study category. The microsecond molecular dynamics (MD) simulations,
      discussed in this work, show that the conformational propensity of the wild type
      XPA67-80 peptide in solution supports conformational selection as the key
      mechanism driving its molecular recognition by ERCC1. Moreover, all the mutations
      of the XPA67-80 peptide studied here cause a significant increase of its
      conformational disorder, relative to the wild type. Comparison to experimental
      data suggests that the loss of the recognized structural motifs at the
      microscopic time scale can contribute to the critical decrease in binding
      observed for one of the mutants, further substantiating the key role of
      conformational selection in recognition. Ultimately, because of the high sequence
      identity and analogy in binding, it is conceivable that the conclusions of this
      study on the XPA67-80 peptide also apply to the ERCC1-binding domain of the XPA
      protein.

PMID- 25973723
TI  - Estimation of Tumor Size Evolution Using Particle Filters.
AB  - Cancer is characterized by the uncontrolled growth of cells with the ability of
      invading local organs and/or tissues and of spreading to other sites. Several
      kinds of mathematical models have been proposed in the literature, involving
      different levels of refinement, for the evolution of tumors and their
      interactions with chemotherapy drugs. In this article, we present the solution of
      a state estimation problem for tumor size evolution. A system of nonlinear
      ordinary differential equations is used as the state evolution model, which
      involves as state variables the numbers of tumor, normal and angiogenic cells, as
      well as the masses of the chemotherapy and anti-angiogenic drugs in the body.
      Measurements of the numbers of tumor and normal cells are considered available
      for the inverse analysis. Parameters appearing in the formulation of the state
      evolution model are treated as Gaussian random variables and their uncertainties
      are taken into account in the estimation of the state variables, by using an
      algorithm based on the auxiliary sampling importance resampling particle filter.
      Test cases are examined in the article dealing with a chemotherapy protocol for
      pancreatic cancer.

PMID- 25973729
TI  - Experimental evaluations of the microchannel flow model.
AB  - Recent advances have enabled a new wave of biomechanics measurements, and have
      renewed interest in selecting appropriate rheological models for soft tissues
      such as the liver, thyroid, and prostate. The microchannel flow model was
      recently introduced to describe the linear response of tissue to stimuli such as
      stress relaxation or shear wave propagation. This model postulates a power law
      relaxation spectrum that results from a branching distribution of vessels and
      channels in normal soft tissue such as liver. In this work, the derivation is
      extended to determine the explicit link between the distribution of vessels and
      the relaxation spectrum. In addition, liver tissue is modified by temperature or
      salinity, and the resulting changes in tissue responses (by factors of 1.5 or
      greater) are reasonably predicted from the microchannel flow model, simply by
      considering the changes in fluid flow through the modified samples. The 2 and 4
      parameter versions of the model are considered, and it is shown that in some
      cases the maximum time constant (corresponding to the minimum vessel diameters),
      could be altered in a way that has major impact on the observed tissue response.
      This could explain why an inflamed region is palpated as a harder bump compared
      to surrounding normal tissue. 

PMID- 25973730
TI  - H-Chain Ferritin: A Natural Nuclei Targeting and Bioactive Delivery Nanovector.

PMID- 25973731
TI  - Description of robotic single site cholecystectomy and a review of outcomes.
AB  - New technologies have been developed to make laparoscopic cholecystectomy less
      invasive through single incision laparoscopic surgery (SILS), however this
      approach has its own limitations. Single incision robotic surgery (SIRC) is
      designed to overcome them. The concerns that limit adoption of this technology
      are attributed increases in costs, prolonged learning curves and surgical times.
      Here, we provide a literature review as well as our own experience with SIRC,
      with the intent to clarify these important concerns.

PMID- 25973732
TI  - Graphitic-Carbon Layers on Oxides: Toward Stable Heterogeneous Catalysts for
      Biomass Conversion Reactions.
AB  - Conversion of biomass-derived molecules involves catalytic reactions under harsh
      conditions in the liquid phase (e.g., temperatures of 250  degrees C and possibly
      under either acidic or basic conditions). Conventional oxide-supported catalysts
      undergo pore structure collapse and surface area reduction leading to
      deactivation under these conditions. Here we demonstrate an approach to deposit
      graphitic carbon to protect the oxide surface. The heterogeneous catalysts
      supported on the graphitic carbon/oxide composite exhibit excellent stability
      (even under acidic conditions) for biomass conversion reactions. 

PMID- 25973733
TI  - Cranberry Xyloglucan Structure and Inhibition of Escherichia coli Adhesion to
      Epithelial Cells.
AB  - Cranberry juice has been recognized as a treatment for urinary tract infections
      on the basis of scientific reports of proanthocyanidin anti-adhesion activity
      against Escherichia coli as well as from folklore. Xyloglucan oligosaccharides
      were detected in cranberry juice and the residue remaining following commercial
      juice extraction that included pectinase maceration of the pulp. A novel
      xyloglucan was detected through tandem mass spectrometry analysis of an ion at
      m/z 1055 that was determined to be a branched, three hexose, four pentose
      oligosaccharide consistent with an arabino-xyloglucan structure. Two-dimensional
      nuclear magnetic resonance spectroscopy analysis provided through-bond
      correlations for the alpha-L-Araf (1->2) alpha-D-Xylp (1->6) beta-D-Glcp
      sequence, proving the S-type cranberry xyloglucan structure. Cranberry xyloglucan
      rich fractions inhibited the adhesion of E. coli CFT073 and UTI89 strains to T24
      human bladder epithelial cells and that of E. coli O157:H7 to HT29 human colonic
      epithelial cells. SSGG xyloglucan oligosaccharides represent a new cranberry
      bioactive component with E. coli anti-adhesion activity and high affinity for
      type 1 fimbriae.

PMID- 25973734
TI  - Scaffolds with shape memory behavior for the treatment of large bone defects.
AB  - The aim of the presented study was preparation, analysis of properties, and in
      vitro characterization of porous shape-memory scaffolds, designed for large bone
      defects treatment using minimally invasive surgery approach. Biodegradable
      terpolymers of l-lactide/glycolide/trimethylene carbonate (LA/GL/TMC) and l
      lactide/glycolide/epsilon-caprolactone (LA/GL/Cap) were selected for formulation
      of these scaffolds. Basic parameters of shape memory behavior (i.e. recovery
      ratio, recovery time) and changes in morphology (SEM, average porosity) and
      properties (surface topography, water contact angle, compressive strength) during
      shape memory cycle were characterized. The scaffolds preserved good mechanical
      properties (compressive strength about 0.7 to 0.9 MPa) and high porosity (more
      than 80%) both in initial shape as well as after return from compressed shape.
      Then the scaffolds in temporary shape were inserted into the model defect of bone
      tissue at 37 degrees C. After 12 min the defect was filled completely as a result
      of shape recovery process induced by body temperature. The scaffold obtained from
      LA/GL/TMC terpolymer was found the most prospective for the planned application
      thanks to its appropriate recovery time, high recovery ratio (more than 90%), and
      cytocompatibility in contact with human osteoblasts and chondrocytes.

PMID- 25973736
TI  - The "Duality" of Idiopathic Ventricular Arrhythmias from the Left Ventricular
      Ostium.

PMID- 25973735
TI  - Achromobacter xylosoxidans Bacteremia and Cellulitis: A Report of a Case.
AB  - Achromobacter xylosoxidans is a rare, opportunistic infection most commonly
      encountered in immunocompromised patients during hospitalization. Primary
      uncomplicated bacteremia, catheter-associated infections, and pneumonia have been
      reported as the most common clinical presentations; skin and soft tissue
      infections from A. xylosoxidans are rare. We describe a case of A. xylosoxidans
      presenting as cellulitis and bacteremia in an immunocompromised patient. 

PMID- 25973737
TI  - Increased Transforming Growth Factor-beta Levels Associated With Cardiac Adverse
      Events in Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease
      characterized by ventricular hypertrophy, myocardial fibrosis, and impaired
      ventricular relaxation. The exact mechanisms by which fibrosis is caused remain
      unknown. HYPOTHESIS: Circulating TGF-beta is related to poor prognosis in HCM.
      METHODS: We compared TGF-beta levels of 49 HCM patients with those of 40 non-HCM
      patients. We followed the patients with HCM for 18 months and divided them into 2
      groups: low TGF-beta (<= 4877 pg/mL) and high TGF-beta (> 4877 pg/mL). We
      compared the 2 groups in terms of brain natriuretic peptide (BNP),
      echocardiographic parameters, and clinical outcomes including myocardial
      infarction, arrhythmias, implantable cardioverter-defibrillator implantation,
      hospitalization, New York Heart Association (NYHA) class, acute heart failure,
      and mortality. RESULTS: The HCM patients had higher TGF-beta levels than those in
      the control group (P = 0.005). In the follow-up, those in the high TGF-beta group
      had higher BNP levels, larger left-atrial size, thicker interventricular septum,
      NYHA class, more hospitalizations, and a greater number of clinical adverse
      events (P < 0.001, P = 0.01, P < 0.001, P = 0.002, P < 0.001 and P = 0.003,
      respectively). TGF-beta level of > 4877 pg/mL can predict adverse events with a
      specificity of 75% and a sensitivity of 72% (P = 0.014). In multivariate
      regression analysis, TGF-beta, BNP, and interventricular septum thickness were
      significantly associated with adverse events (P = 0.028, P = 0.030, and P =
      0.034, respectively). CONCLUSIONS: The TGF-beta level is higher in HCM patients
      and associated with a poor prognosis in HCM.

PMID- 25973738
TI  - Interfacial Assembly of Surfactant-Decorated Nanoparticles: On the Rheological
      Description of a Colloidal 2D Glass.
AB  - We address the rheology of assemblies of surfactant-decorated silica
      nanoparticles irreversibly adsorbed at the gas/liquid interface. Positively
      charged surfactant molecules (such as CTAB) bind to silica nanoparticle surfaces,
      and the resulting particle-surfactant complexes adsorb at gas/liquid interfaces.
      The surfactant molecules control the wettability of such decorated nanoparticles
      and their adsorption. The interparticle forces can be tuned by changing the
      surfactant concentration Cs. Increasing Cs, in addition to a decrease of the
      particles wettability, leads to an increase of the area fraction of particles at
      the interface. Oscillatory shear measurements (strain- and frequency-sweep) have
      been performed. Here, we explore the effect of the surfactant concentration Cs.
      At high enough Cs, the interface is highly packed, and an overall solidlike
      response is observed, with 2D glass properties. 

PMID- 25973740
TI  - Two-voxel spectroscopy with dynamic B0 shimming and flip angle adjustment at 7 T
      in the human motor cortex.
AB  - The aim of this study was to acquire high-quality in vivo (1) H spectra
      concurrently from two voxels at ultra-high field (7 T) without specialized
      hardware. To this end, an acquisition scheme was developed in which first-order
      shims and flip angles are dynamically updated to acquire spectra from both of the
      brain's motor cortices in an alternating fashion. To validate this acquisition
      scheme, separate, static, single-voxel acquisitions were also performed for
      comparison. Six subjects were examined using semi-LASER spectroscopy at 7 T.
      Barium titanate pads were used to increase the extent of the effective transmit
      field (B1 (+) ). Spectra were obtained from the hand area of both motor cortices
      for both acquisition schemes. LCModel was used to determine neurochemical
      profiles in order to examine variations between acquisition schemes and volumes
      of interest. The dynamic two-voxel acquisition protocol produced water linewidths
      (full width at half-maximum between 11.6 and 12.8 Hz) and signal-to-noise ratios
      similar to those from static single-voxel measurements. The concentrations of 13
      individual and 3 combined metabolites with Cramer-Rao lower bounds below 30% were
      reliably detected for both acquisition schemes, and agreed well with previous
      postmortem assay and spectroscopy studies. The results show that high spectral
      quality from two voxels can be acquired concurrently without specialized
      hardware. This practical technique can be applied to many neuroscience
      applications.

PMID- 25973739
TI  - Multiscale Modeling of Drug-induced Effects of ReDuNing Injection on Human
      Disease: From Drug Molecules to Clinical Symptoms of Disease.
AB  - ReDuNing injection (RDN) is a patented traditional Chinese medicine, and the
      components of it were proven to have antiviral and important anti-inflammatory
      activities. Several reports showed that RDN had potential effects in the
      treatment of influenza and pneumonia. Though there were several experimental
      reports about RDN, the experimental results were not enough and complete due to
      that it was difficult to predict and verify the effect of RDN for a large number
      of human diseases. Here we employed multiscale model by integrating molecular
      docking, network pharmacology and the clinical symptoms information of diseases
      and explored the interaction mechanism of RDN on human diseases. Meanwhile, we
      analyzed the relation among the drug molecules, target proteins, biological
      pathways, human diseases and the clinical symptoms about it. Then we predicted
      potential active ingredients of RDN, the potential target proteins, the key
      pathways and related diseases. These attempts may offer several new insights to
      understand the pharmacological properties of RDN and provide benefit for its new
      clinical applications and research. 

PMID- 25973741
TI  - Structural Differences between Wild-Type and Double Mutant EGFR Modulated by
      Third-Generation Kinase Inhibitors.
AB  - Mutations in the EGFR kinase domain are implicated in non-small-cell lung cancer.
      Of particular interest is the drug-resistant double mutant (L858R/T790M, DM
      EGFR), which is not inhibited selectively by any approved kinase inhibitor. Here
      we apply bipartite tetracysteine display to demonstrate that DM and WT EGFR
      differ in structure outside the kinase domain. The structural difference is
      located within the cytoplasmic juxtamembrane segment (JM) that links the kinase
      domain with the extracellular and transmembrane regions and is essential for EGFR
      activation. We show further that third-generation DM EGFR-selective TKIs alter JM
      structure via allostery to restore the conformation found when WT EGFR is
      activated by the growth factors EGF and HB-EGF. This work suggests that the
      oncogenic activity of DM EGFR may extend beyond kinase activity per se to include
      kinase-independent activities. As JM structure may provide a biomarker for these
      kinase-independent functions, these insights could guide the development of
      allosteric, DM-selective inhibitors. 

PMID- 25973742
TI  - Role for Artemis nuclease in the repair of radiation-induced DNA double strand
      breaks by alternative end joining.
AB  - Exposure of cells to ionizing radiation or radiomimetic drugs generates DNA
      double-strand breaks that are processed either by homologous recombination repair
      (HRR), or by canonical, DNA-PKcs-dependent non-homologous end-joining (C-NHEJ).
      Chemical or genetic inactivation of factors involved in C-NHEJ or HRR, but also
      their local failure in repair proficient cells, promotes an alternative, error
      prone end-joining pathway that serves as backup (A-EJ). There is evidence for the
      involvement of Artemis endonuclease, a protein deficient in a human
      radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in
      the processing of subsets of DSBs by HRR or C-NHEJ. It is thought that within HRR
      or C-NHEJ Artemis processes DNA termini at complex DSBs. Whether Artemis has a
      role in A-EJ remains unknown. Here, we analyze using pulsed-field gel
      electrophoresis (PFGE) and specialized reporter assays, DSB repair in wild-type
      pre-B NALM-6 lymphocytes, as well as in their Artemis(-/-), DNA ligase 4(-/-)
      (LIG4(-/-)), and LIG4(-/-)/Artemis(-/-) double mutant counterparts, under
      conditions allowing evaluation of A-EJ. Our results substantiate the suggested
      roles of Artemis in C-NHEJ and HRR, but also demonstrate a role for the protein
      in A-EJ that is confirmed in Artemis deficient normal human fibroblasts. We
      conclude that Artemis is a nuclease participating in DSB repair by all major
      repair pathways. 

PMID- 25973743
TI  - Telomere length in interstitial lung diseases.
AB  - BACKGROUND: Interstitial lung disease (ILD) is a heterogeneous group of rare
      diseases that primarily affect the pulmonary interstitium. Studies have
      implicated a role for telomere length (TL) maintenance in ILD, particularly in
      idiopathic interstitial pneumonia (IIP). Here, we measure TL in a wide spectrum
      of sporadic and familial cohorts of ILD and compare TL between patient cohorts
      and control subjects. METHODS: A multiplex quantitative polymerase chain reaction
      method was used to measure TL in 173 healthy subjects and 359 patients with
      various ILDs, including familial interstitial pneumonia (FIP). The FIP cohort was
      divided into patients carrying TERT mutations, patients carrying SFTPA2 or SFTPC
      mutations, and patients without a proven mutation (FIP-no mutation). RESULTS: TL
      in all cases of ILD was significantly shorter compared with those of control
      subjects (P range: .038 to < .0001). Furthermore, TL in patients with idiopathic
      pulmonary fibrosis (IPF) was significantly shorter than in patients with other
      IIPs (P = .002) and in patients with sarcoidosis (P < .0001). Within the FIP
      cohort, patients in the FIP-telomerase reverse transcriptase (TERT) group had the
      shortest telomeres (P < .0001), and those in the FIP-no mutation group had TL
      comparable to that of patients with IPF (P = .049). Remarkably, TL of patients
      with FIP-surfactant protein (SFTP) was significantly longer than in patients with
      IPF, but similar to that observed in patients with other sporadic IIPs.
      CONCLUSIONS: The results show telomere shortening across all ILD diagnoses. The
      difference in TL between the FIP-TERT and FIP-SFTP groups indicates the
      distinction between acquired and innate telomere shortening. Short TL in the IPF
      and FIP-no mutation groups is indicative of an innate telomere-biology defect,
      while a stress-induced, acquired telomere shortening might be the underlying
      process for the other ILD diagnoses.

PMID- 25973744
TI  - Combined effects of organic acids and salt depending on type of acids and
      pathogens in laboratory media and acidified pickle.
AB  - AIM: In this study, the effectiveness of combining each of seven types of acids
      with 3% salt as a treatment against pathogens was investigated in laboratory
      media and acidified food. METHODS AND RESULTS: When 0.5% malic, 0.5% tartaric,
      0.5% citric or 0.25% phosphoric acid was combined with 3% salt, there was a
      higher reduction in Gram-negative bacteria (Escherichia coli O157:H7 and
      Salmonella Typhimurium) compared to when using acid alone. However, when 0.5%
      acetic, 0.5% propionic or 0.25% lactic acid was combined with 3% salt, the salt
      provided protection against the acid treatment. However, the antagonistic effects
      of acetic, propionic and lactic acid seen with Gram-negative bacteria were not
      observed in Listeria monocytogenes. Antagonistic effects were similarly observed
      when E. coli O157:H7 was treated with acetic acid and salt in food. CONCLUSIONS:
      These results show that the addition of salt increases the resistance of Gram
      negative bacteria to acid treatments when using acetic, propionic and lactic
      acid. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that antagonistic
      effects were observed when Gram-negative bacteria were treated with organic acids
      of simple structure. It may provide useful information for understanding the acid
      resistance mechanism of Gram-negative bacteria and developing methods for
      preserving acidified food.

PMID- 25973745
TI  - Structure and Energetics of Complexes of B12N12 with Hydrogen Halides-SAPT(DFT)
      and MP2 Study.
AB  - Molecular complexes of a fullerene analogue B12N12 with hydrogen halides (HCl,
      HBr, and HI) were studied with symmetry-adapted perturbation theory with density
      functional theory applied for a description of monomers (SAPT(DFT)), Moller
      Plesset theory to the second order (MP2), and its spin-component-scaled variant
      (SCS-MP2) in a limit of a complete basis set. For each halide five symmetry
      distinct minimum structures of the complex have been found on the potential
      energy hypersurface, with interaction energies ranging from -6 to -18 kJ/mol. The
      natural bond orbital and the atom-in-molecules analysis of noncovalent bonds
      resulted in a division of these configurations into three categories: hydrogen
      bonded, halogen-bonded, and those of a mixed type, involving simultaneously a
      hydrogen bonding and a pi-hole bonding between halogen and boron atoms. A
      comparison of various approaches for the calculation of interaction energies
      shows that the SCS-MP2 supermolecular method gives results which are in a close
      agreement with SAPT(DFT), while the MP2 interaction energies are systematically
      more negative than the SAPT values. The ability of the B12N12 nanocage to bind
      hydrogen halides through several active sites on its surface puts under question
      the selectivity of the binding necessary in crystal engineering, especially for
      the hydrogen bromide and hydrogen iodide cases, which show small differences in
      stabilization energies for their minimum structures. The directionality of
      noncovalent bonds is explained on grounds of the anisotropy of some SAPT
      components, like electrostatics and induction, as well as by the sigma-hole and
      pi-hole models. 

PMID- 25973746
TI  - Dynamics and Reversibility of the DNA Methylation Landscape of Grapevine Plants
      (Vitis vinifera) Stressed by In Vitro Cultivation and Thermotherapy.
AB  - There is relatively little information concerning long-term alterations in DNA
      methylation following exposure of plants to environmental stress. As little is
      known about the ratio of non-heritable changes in DNA methylation and mitotically
      inherited methylation changes, dynamics and reversibility of the DNA methylation
      states were investigated in grapevine plants (Vitis vinifera) stressed by in
      vitro cultivation. It was observed that significant part of induced epigenetic
      changes could be repeatedly established by exposure to particular planting and
      stress conditions. However, once stress conditions were discontinued, many
      methylation changes gradually reverted and plants returned to epigenetic states
      similar to those of maternal plants. In fact, in the period of one to three years
      after in vitro cultivation it was difficult to distinguish the epigenetic states
      of somaclones and maternal plants. Forty percent of the observed epigenetic
      changes disappeared within a year subsequent to termination of stress conditions
      ending and these probably reflect changes caused by transient and reversible
      stress-responsive acclimation mechanisms. However, sixty percent of DNA
      methylation diversity remained after 1 year and probably represents mitotically
      inherited epimutations. Sequencing of regions remaining variable between maternal
      and regenerant plants revealed that 29.3% of sequences corresponded to non-coding
      regions of grapevine genome. Eight sequences (19.5%) corresponded to previously
      identified genes and the remaining ones (51.2%) were annotated as "hypothetical
      proteins" based on their similarity to genes described in other species,
      including genes likely to undergo methylation changes following exposure to
      stress (V. vinifera gypsy-type retrotransposon Gret1, auxin-responsive
      transcription factor 6-like, SAM-dependent carboxyl methyltransferase). 

PMID- 25973749
TI  - C(sp(3))-C(sp(3)) bond cleavage in the palladium-catalyzed aminohydroxylation of
      allylic hydrazones using atmospheric oxygen as the sole oxidant.
AB  - A C-C bond cleavage was observed in the palladium-catalyzed aminohydroxylation of
      allylic hydrazones, using atmospheric oxygen as the sole oxidant. This reaction
      could also proceed in a one-pot manner, starting from keto-alkene compounds and
      phenylhydrazine. 

PMID- 25973748
TI  - Cell Surface GRP78 Accelerated Breast Cancer Cell Proliferation and Migration by
      Activating STAT3.
AB  - High levels of cell surface glucose regulated protein 78 (sGRP78) have been
      implicated in cancer growth, survival, metastasis, and chemotherapy resistance.
      However, the underlying mechanism remains largely unknown. Here we report that
      the level of sGRP78 expression in human breast tumors gradually increases during
      cancer progression. Overexpression of GRP78 significantly enhanced its membrane
      distribution in human MCF-7 breast cancer cells, but had no effect on endoplasmic
      reticulum (ER) stress. High levels of sGRP78 facilitated cell proliferation and
      migration, as well as suppressed cell apoptosis. Neutralization of sGRP78 by a
      specific antibody against GRP78 alleviated sGRP78-induced cell growth and
      migration. Importantly, high phosphorylation levels of the signal transducer and
      activator of transcription 3 (STAT3) were found in human breast tumors that
      express sGRP78 and MCF-7 cells infected with adenovirus encoding human GRP78.
      Pretreatment with a GRP78 antibody suppressed STAT3 phosphorylation. Furthermore,
      genetic and pharmacological inhibition of STAT3 reversed the impacts of GRP78 on
      cell proliferation, apoptosis, and migration. These findings indicate that STAT3
      mediates sGRP78-promoted breast cancer cell growth and migration. 

PMID- 25973750
TI  - Correction: Cytokine-Induced Loss of Glucocorticoid Function: Effect of Kinase
      Inhibitors, Long-Acting beta2-Adrenoceptor Agonist and Glucocorticoid Receptor
      Ligands.

PMID- 25973747
TI  - High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic
      Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive
      Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor
      and Statin.
AB  - Cardiovascular diseases (CVDs) are significantly high in the Lebanese population
      with the two most predominant forms being atherosclerosis and venous thrombosis.
      The purpose of our study was to assess the association of a spectrum of CVD
      related genes and combined state of hypertension hypercholesterolemia (HH) in
      unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and
      reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects.
      Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI
      1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles
      "Del" and "4G". The frequencies of the Del and 4G alleles were found to be 0.98
      and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively.
      Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G
      genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171
      (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected
      in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis
      related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly
      related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8
      combined polymorphisms co-expressed per subject where 5 mutations were the most
      detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs)
      produced significant elevated levels of IFN-gamma and TNF-alpha contrary to IL
      10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination
      with statin (atorvastatin) and not alone reversed significantly the situation.
      This first report from Lebanon sheds light on an additional genetic
      predisposition of a complex spectrum of genes involved in CVD and suggests that
      the most requested gene FVL by physicians may not be sufficient to diagnose
      eventual future problems that can occur in the cardiovascular system. Subjects
      expressing the double mutations (Del/4G) are at high risk for the onset of CVDs. 

PMID- 25973751
TI  - Correction: CD8 T Cell Response Maturation Defined by Anentropic Specificity and
      Repertoire Depth Correlates with SIVDeltanef-induced Protection.

PMID- 25973752
TI  - House Dust Mite Allergen Regulates Constitutive Apoptosis of Normal and Asthmatic
      Neutrophils via Toll-Like Receptor 4.
AB  - House dust mites (HDMs) induce allergic diseases such as asthma. Neutrophil
      apoptosis is an important process of innate immunity, and its dysregulation is
      associated with asthma. In this study, we examined the effects of HDM on
      constitutive apoptosis of normal and asthmatic neutrophils. Extract of
      Dermatophagoides pteronissinus (DP) inhibited neutrophil apoptosis, but
      Dermatophagoides farinae extract had no effect. Anti-apoptotic signaling mediated
      by DP involves in TLR4, Lyn, PI3K, Akt, ERK, and NF-kappaB in normal neutrophils.
      DP delayed cleavage of procaspase 9 and procaspase 3 and the decrease in Mcl-1
      expression. Supernatant collected from DP-treated normal neutrophils inhibited
      the constitutive apoptosis of normal neutrophils, and S100A8 and S100A9 were
      identified as anti-apoptotic proteins in the supernatant. S100A8 and S100A9
      transduced the anti-apoptotic signal via TLR4, Lyn, PI3K, Akt, ERK, and NF
      kappaB. DP also suppressed asthmatic neutrophil apoptosis and induced secretion
      of S100A8 and S100A9, which delayed the constitutive apoptosis. The anti
      apoptotic effects of DP, S100A8 and S100A9 in asthmatic neutrophils are
      associated with TLR4, Lyn, PI3K, Akt, ERK, and NF-kappaB. The concentrations of
      S100A8 and S100A9 were significantly elevated in asthmatic bronchoalveolar lavage
      fluid (BALF) when compared to normal BALF (p<0.01), but not in serum. S100A8
      concentration in BALF was positively correlated with the number of BALF
      neutrophils and negatively correlated with FEV1(%). These findings improve our
      understanding of the role of HDM in regulation of neutrophil apoptosis in normal
      individuals and asthmatics and will enable elucidation of asthma pathogenesis.

PMID- 25973754
TI  - Modeling occupancy of hosts by mistletoe seeds after accounting for imperfect
      detectability.
AB  - The detection of an organism in a given site is widely used as a state variable
      in many metapopulation and epidemiological studies. However, failure to detect
      the species does not necessarily mean that it is absent. Assessing detectability
      is important for occupancy (presence-absence) surveys; and identifying the
      factors reducing detectability may help improve survey precision and efficiency.
      A method was used to estimate the occupancy status of host trees colonized by
      mistletoe seeds of Psittacanthus plagiophyllus as a function of host covariates:
      host size and presence of mistletoe infections on the same or on the nearest
      neighboring host (the cashew tree Anacardium occidentale). The technique also
      evaluated the effect of taking detectability into account for estimating host
      occupancy by mistletoe seeds. Individual host trees were surveyed for presence of
      mistletoe seeds with the aid of two or three observers to estimate detectability
      and occupancy. Detectability was, on average, 17% higher in focal-host trees with
      infected neighbors, while decreased about 23 to 50% from smallest to largest
      hosts. The presence of mistletoe plants in the sample tree had negligible effect
      on detectability. Failure to detect hosts as occupied decreased occupancy by 2.5%
      on average, with maximum of 10% for large and isolated hosts. The method
      presented in this study has potential for use with metapopulation studies of
      mistletoes, especially those focusing on the seed stage, but also as improvement
      of accuracy in occupancy models estimates often used for metapopulation dynamics
      of tree-dwelling plants in general. 

PMID- 25973753
TI  - Prospects for malaria elimination in Mesoamerica and Hispaniola.
AB  - Malaria remains endemic in 21 countries of the American continent with an
      estimated 427,000 cases per year. Approximately 10% of these occur in the
      Mesoamerican and Caribbean regions. During the last decade, malaria transmission
      in Mesoamerica showed a decrease of ~85%; whereas, in the Caribbean region,
      Hispaniola (comprising the Dominican Republic [DR] and Haiti) presented an
      overall rise in malaria transmission, primarily due to a steady increase in
      Haiti, while DR experienced a significant transmission decrease in this period.
      The significant malaria reduction observed recently in the region prompted the
      launch of an initiative for Malaria Elimination in Mesoamerica and Hispaniola
      (EMMIE) with the active involvement of the National Malaria Control Programs
      (NMCPs) of nine countries, the Regional Coordination Mechanism (RCM) for
      Mesoamerica, and the Council of Health Ministries of Central America and
      Dominican Republic (COMISCA). The EMMIE initiative is supported by the Global
      Fund for Aids, Tuberculosis and Malaria (GFATM) with active participation of
      multiple partners including Ministries of Health, bilateral and multilateral
      agencies, as well as research centers. EMMIE's main goal is to achieve
      elimination of malaria transmission in the region by 2020. Here we discuss the
      prospects, challenges, and research needs associated with this initiative that,
      if successful, could represent a paradigm for other malaria-affected regions. 

PMID- 25973755
TI  - Bringing statistics up to speed with data in analysis of lymphocyte motility.
AB  - Two-photon (2P) microscopy provides immunologists with 3D video of the movement
      of lymphocytes in vivo. Motility parameters extracted from these videos allow
      detailed analysis of lymphocyte motility in lymph nodes and peripheral tissues.
      However, standard parametric statistical analyses such as the Student's t-test
      are often used incorrectly, and fail to take into account confounds introduced by
      the experimental methods, potentially leading to erroneous conclusions about T
      cell motility. Here, we compare the motility of WT T cell versus PKCtheta-/-,
      CARMA1-/-, CCR7-/-, and PTX-treated T cells. We show that the fluorescent dyes
      used to label T cells have significant effects on T cell motility, and we
      demonstrate the use of factorial ANOVA as a statistical tool that can control for
      these effects. In addition, researchers often choose between the use of "cell
      based" parameters by averaging multiple steps of a single cell over time (e.g.
      cell mean speed), or "step-based" parameters, in which all steps of a cell
      population (e.g. instantaneous speed) are grouped without regard for the cell
      track. Using mixed model ANOVA, we show that we can maintain cell-based analyses
      without losing the statistical power of step-based data. We find that as we use
      additional levels of statistical control, we can more accurately estimate the
      speed of T cells as they move in lymph nodes as well as measure the impact of
      individual signaling molecules on T cell motility. As there is increasing
      interest in using computational modeling to understand T cell behavior in in
      vivo, these quantitative measures not only give us a better determination of
      actual T cell movement, they may prove crucial for models to generate accurate
      predictions about T cell behavior. 

PMID- 25973758
TI  - Applying the evidence to help caregivers torn in two.

PMID- 25973757
TI  - Suppression of autoimmunity by CD5(+) IL-10-producing B cells in lupus-prone
      mice.
AB  - Systemic lupus erythematosus is a complex autoimmune disorder characterized by
      the production of pathogenic anti-nuclear antibodies. Previous work from our
      laboratory has shown that the introgression of a New Zealand Black-derived
      chromosome 4 interval onto a lupus-prone background suppresses the disease.
      Interestingly, the same genetic interval promoted the expansion of both Natural
      Killer T- and CD5(+) B cells in suppressed mice. In this study, we show that
      ablation of NKT cells with a CD1d knockout had no impact on either the
      suppression of lupus or the expansion of CD5(+) B cells. On the other hand,
      suppressed mice had an expanded population of IL-10-producing B cells that
      predominantly localized to the CD5(+)CD1d(low) compartment. The expansion of
      CD5(+) B cells negatively correlated with the frequency of pro-inflammatory IL-17
      A-producing T-cells and kidney damage. Adoptive transfer with a single injection
      of total B cells with an enriched CD5(+) compartment reduced the frequency of
      memory/activated, IFNgamma-producing, and IL-17 A-producing CD4 T-cells but did
      not significantly reduce autoantibody levels. Taken together, these data suggest
      that the expansion of CD5(+) IL-10-producing B cells and not NKT cells protects
      against lupus in these mice, by limiting the expansion of pro-inflammatory IL-17
      A- and IFNgamma-producing CD4 T-cells. 

PMID- 25973756
TI  - Brucella spp. Lumazine Synthase Induces a TLR4-Mediated Protective Response
      against B16 Melanoma in Mice.
AB  - Brucella Lumazine Synthase (BLS) is a highly immunogenic decameric protein which
      can accept the fusion of foreign proteins at its ten N-termini. These chimeras
      are very efficient to elicit systemic and oral immunity without adjuvants. BLS
      signaling via Toll-Like Receptor 4 (TLR4) regulates innate and adaptive immune
      responses, inducing dendritic cell maturation and CD8(+) T-cell cytotoxicity. In
      this work we study the effect induced by BLS in TLR4-expressing B16 melanoma. In
      order to evaluate the effectiveness of BLS as a preventive vaccine, C57BL/6J mice
      were immunized with BLS or BLS-OVA, and 35 days later were subcutaneously
      inoculated with B16-OVA melanoma. BLS or BLS-OVA induced a significant inhibition
      of tumor growth, and 50% of mice immunized with the highest dose of BLS did not
      develop visible tumors. This effect was not observed in TLR4-deficient mice. For
      treatment experiments, mice were injected with BLS or BLS-OVA 2 days after the
      inoculation of B16 cells. Both treatments induced significant and equal tumor
      growth delay and increased survival. Moreover, BLS and BLS-OVA stimulation were
      also effective in TLR4-deficient mice. In order to study whether BLS has a direct
      effect on tumor cells, B16 cells were preincubated with BLS, and after 48h, cells
      were inoculated. Tumors induced by BLS-stimulated cells had inhibited growth and
      survival was increased. In the BLS group, 40% of mice did not develop tumors.
      This effect was abolished by the addition of TLR4/MD2 blocking antibody to cells
      before BLS stimulation. Our work demonstrates that BLS immunization induces a
      preventive antitumor response that depends on mice TLR4. We also show that BLS
      generates a therapeutic effect in mice inoculated with B16 cells. Our results
      show that BLS acts directly in cultured tumor cells via TLR4, highly suggesting
      that BLS elicits its therapeutic effects acting on the TLR4 from B16 melanoma
      cells.

PMID- 25973759
TI  - Self-assembled penetratin-deferasirox micelles as potential carriers for
      hydrophobic drug delivery.
AB  - There has been a growing interest in the use of micelles with nanofiber geometry
      as nanocarriers for hydrophobic drugs. Here we show that the conjugate of
      penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB)
      permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles
      to form micelles at a very low concentration (~15 mg/L). The critical micelle
      concentration (CMC) was determined, and the micelles were used for solubilizing
      curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery
      across RBE4 cells, a BBB model. Transmission Electron Microscope images of the
      curcumin-loaded micelles confirmed the formation of nanofibers. These results
      indicate the potential of CPP-drug conjugates for use as nanocarriers.

PMID- 25973760
TI  - Characterization of a Single-Stranded DNA-Binding-Like Protein from Nanoarchaeum
      equitans--A Nucleic Acid Binding Protein with Broad Substrate Specificity.
AB  - BACKGROUND: SSB (single-stranded DNA-binding) proteins play an essential role in
      all living cells and viruses, as they are involved in processes connected with
      ssDNA metabolism. There has recently been an increasing interest in SSBs, since
      they can be applied in molecular biology techniques and analytical methods.
      Nanoarchaeum equitans, the only known representative of Archaea phylum
      Nanoarchaeota, is a hyperthermophilic, nanosized, obligatory parasite/symbiont of
      Ignicoccus hospitalis. RESULTS: This paper reports on the ssb-like gene cloning,
      gene expression and characterization of a novel nucleic acid binding protein from
      Nanoarchaeum equitans archaeon (NeqSSB-like protein). This protein consists of
      243 amino acid residues and one OB fold per monomer. It is biologically active as
      a monomer like as SSBs from some viruses. The NeqSSB-like protein displays a low
      sequence similarity to the Escherichia coli SSB, namely 10% identity and 29%
      similarity, and is the most similar to the Sulfolobus solfataricus SSB (14%
      identity and 32% similarity). The NeqSSB-like protein binds to ssDNA, although it
      can also bind mRNA and, surprisingly, various dsDNA forms, with no structure
      dependent preferences as evidenced by gel mobility shift assays. The size of the
      ssDNA binding site, which was estimated using fluorescence spectroscopy, is 7 +/-
      1 nt. No salt-dependent binding mode transition was observed. NeqSSB-like protein
      probably utilizes a different model for ssDNA binding than the SSB proteins
      studied so far. This protein is highly thermostable; the half-life of the ssDNA
      binding activity is 5 min at 100  degrees C and melting temperature (T(m)) is
      100.2  degrees C as shown by differential scanning calorimetry (DSC) analysis.
      CONCLUSION: NeqSSB-like protein is a novel highly thermostable protein which
      possesses a unique broad substrate specificity and is able to bind all types of
      nucleic acids.

PMID- 25973761
TI  - IP-10 Serum Level in Chronic Hepatitis C Virus Patients: Relation to Fibrosis and
      Response to Combined Interferon/Ribavirin Therapy.
AB  - Despite the appearance of the direct acting antiviral drugs, pegylated
      interferon/ribavirin (PEG-IFN/RBV) still has a place in the standard of care
      (SOC) therapy for chronic HCV4. Studies were conducted to find an accurate
      prediction in response to SOC therapy. Pretreatment serum interferon-gamma
      inducible protein-10 (IP-10) is an independent predictive factor of sustained
      virological response (SVR) in HCV1-infected patients. To assess whether the
      pretreatment serum level of IP-10 influences hepatic fibrosis and PEG-IFN/RBV
      therapy response, a study was conducted on 88 chronic Hepatitis C virus (HCV)
      patients who received PEG-IFN/RBV. Patients were subjected to a pretreatment
      routine laboratory evaluation, liver biopsy, and serum IP-10 assessment. They
      were followed up for 6 months after cessation of therapy (week 72). Patients were
      classified into 3 groups according to their response; nonresponders, relapsers,
      or sustained virological responders. The relation of pretreatment IP-10 with
      fibrosis and response was assessed. The studied groups were matched regarding
      their demographic data. There was no statistically significant association
      between the pretreatment IP-10 level and fibrosis (P=0.86) and no relation to
      response was found at week 12, 24, 48, and 72 (P=0.58, 0.8, 0.47, and 0.43,
      respectively). Pretreatment IP-10 could not predict either fibrosis or response
      to PEG-IFN/RIB therapy in chronic HCV Egyptian patients. 

PMID- 25973762
TI  - Conformation and activity of lipase B from Candida antarctica in bicontinuous
      microemulsions.
AB  - The paper at hand deals with the influence of the pH-value on the conformation
      and activity of the lipase B from Candida antarctica (CalB) which is incorporated
      in a bicontinuous microemulsion. The microemulsion used for this purpose consists
      of water/NaCl, n-octane, and the non-ionic surfactant penthaethylene glycol
      monodecylether (C10E5). The conformational study clearly shows (1) that CalB
      molecules are partitioned between the interfacial monolayer and the water domains
      and (2) that the pH-value of the microemulsion's water domains strongly
      influences the conformation of CalB at the interfacial monolayer. From these
      observations we conclude that there is a continuous exchange between the CalB
      molecules, which are located at the interfacial monolayer and those which are
      located in the water domains of the microemulsion. This exchange strongly
      influences the CalB conformation in both regions. In addition to the
      conformation, we also studied the catalytic activity of CalB. The catalytic
      measurements revealed a bell-shaped dependence between the CalB activity and the
      pH-value. The maximum catalytic activity of CalB in bicontinuous microemulsions
      was observed at pH=5.5. At this pH we observed the highest amount of alpha-helix
      conformation of the CalB molecules that are located at the interfacial monolayer,
      which, in turn, allows connecting the activity with the conformation. 

PMID- 25973763
TI  - Crowding enhances lipase turnover rate on surface-immobilized substrates.
AB  - Utilizing surface-immobilized synthetic lipid substrates containing the redox
      active ferrocene groups, the enzymatic activity of lipase from Thermomyces
      lanuginosus was measured by the cyclic voltammetry method. The activity was
      correlated with the surface density of the protein by the ATR-IR spectroscopy and
      the total internal reflection ellipsometry. It was found that the lipase turnover
      rate significantly increases with its surface density. Despite expected hindrance
      effects due to the crowding of the enzyme molecules in the near surface
      saturation range of concentrations, the turnover rate was consistently higher
      compared with the values measured at low concentrations. The effect was explained
      by the change in the surface arrangement of the enzyme. In the low concentration
      range, lipase adsorbs onto a surface adopting a predominantly horizontal
      position. At high concentrations, as the surface density approaches saturation,
      the enzyme molecules due to crowding are forced into the predominantly vertical
      position, which is more favorable for the activation of the lipase through the
      interaction between the "hydrophobic lid" of the lipase and the hydrophobic
      adsorbate surface. 

PMID- 25973764
TI  - Numerous but rare: an exploration of magic squares.
AB  - How rare are magic squares? So far, the exact number of magic squares of order n
      is only known for n <= 5. For larger squares, we need statistical approaches for
      estimating the number. For this purpose, we formulated the problem as a
      combinatorial optimization problem and applied the Multicanonical Monte Carlo
      method (MMC), which has been developed in the field of computational statistical
      physics. Among all the possible arrangements of the numbers 1; 2, ..., n(2) in an
      n * n square, the probability of finding a magic square decreases faster than the
      exponential of n. We estimated the number of magic squares for n <= 30. The
      number of magic squares for n = 30 was estimated to be 6.56(29) * 10(2056) and
      the corresponding probability is as small as 10(-212). Thus the MMC is effective
      for counting very rare configurations.

PMID- 25973766
TI  - Novel Instrument for Automated pK(a) Determination by Internal Standard Capillary
      Electrophoresis.
AB  - The internal standard capillary electrophoresis method (IS-CE) has been
      implemented in a novel sequential injection-capillary electrophoresis instrument
      for the high-throughput determination of acidity constants (pK(a)) regardless of
      aqueous solubility, number of pK(a) values, or structure. This instrument
      comprises a buffer creation system that automatically mixes within a few seconds
      four reagents for in situ creation of the separation electrolyte with a pH range
      of 2-13, ionic strength of 10-100 mM and organic solvent content from 0% to 40%.
      Combined with 1.2 kV/cm and a short effective length (15 cm to the UV detector)
      fast 20 s electrophoretic separations can be obtained. The low standard deviation
      of the replicates and the low variation compared to reference values show that
      this system can accurately determine acidity constants of drugs by IS-CE. A
      single pK(a) can be determined in 2 min and a set of 20 measurements in half an
      hour, allowing rapid, simple, and flexible determination of pK(a) values of
      pharmaceutical targets.

PMID- 25973765
TI  - Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal
      Transmission in Humans.
AB  - Recent reports have questioned the accepted dogma that mammalian mitochondrial
      DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on
      detecting a signature of inter-molecular recombination in mtDNA sequences sampled
      at the population level, inferring a paternal source for the mixed haplotypes.
      However, interpreting these data is fraught with difficulty, and direct
      experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up
      to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes
      are transmitted to offspring in humans, thus excluding a simple dilution
      mechanism for uniparental transmission of mtDNA present in all healthy
      individuals. Our findings indicate that an active mechanism eliminates paternal
      mtDNA which likely acts at the molecular level. 

PMID- 25973767
TI  - Field-effect transistors based on amorphous black phosphorus ultrathin films by
      pulsed laser deposition.
AB  - Amorphous black phosphorus (a-BP) ultrathin films are deposited by pulsed laser
      deposition. a-BP field-effect trans-istors, exhibiting high carrier mobility and
      moderate on/off current ratio, are demonstrated. Thickness dependence of the
      bandgap, mobility, and on/off ratio are observed. These results offer not only a
      new nanoscale member in the BP family, but also a new opportunity to develop nano
      electronic devices. 

PMID- 25973768
TI  - Episodic Visual Learning/Memory and Attentional Flexibility in Patients With
      Major Depressive Disorder After Clinically Effective Electroconvulsive Therapy.
AB  - OBJECTIVES: This study is a follow-up of a previous one reporting that the
      neuropsychological profile of pharmacoresistant patients with major depressive
      disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with
      that of their pharmacorespondent counterparts (NECT group). The NECT group
      exhibited severe visuospatial memory and minor executive deficits; the ECT group
      presented the reverse pattern. In that same ECT group, the current follow-up
      study examined the effects of clinically effective ECT on both cognitive domains
      2 months later. METHODS: Fifteen ECT patients were administered Hamilton
      Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination
      Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at
      intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow
      up). RESULTS: Electroconvulsive therapy was effective in relieving clinical
      depression. After a post-ECT decline, the patients exhibited significant
      improvement in both Cambridge Neuropsychological Test Automated Battery, paired
      associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT
      deficit in intra/extradimensional set shifting remained virtually unaffected.
      CONCLUSIONS: Our findings suggest that attentional flexibility deficits may
      constitute a neuropsychological trait-like feature of pharmacoresistant, ECT
      referred major depressive disorder patients. However, this deficit does not seem
      generalized, given patient improvement in episodic visual learning/memory and
      some indication of improvement in spatial planning after ECT.

PMID- 25973770
TI  - Flatliner Notes: Troubleshooting a Faulty EEG Recording or a Case of Preictal
      Suppression?
AB  - Modern electroconvulsive therapy devices are largely trouble free but will
      periodically malfunction. We present a systematic approach to correction of a
      failure in the electroencephalogram recording capability of our Thymatron System
      IV machine. 

PMID- 25973769
TI  - Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register
      for ECT.
AB  - OBJECTIVES: The use of electroconvulsive therapy (ECT) varies across countries.
      The aim of this study was to describe and explore the use of ECT in Sweden in
      2013. METHODS: The Swedish mandatory patient register of the National Board of
      Health and Welfare includes information on diagnoses and treatments, including
      ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory
      national quality register for ECT, which contains information on patient and
      treatment characteristics. In this study, we combined data from both registers.
      In addition, all hospitals responded to a survey concerning equipment and
      organization of ECT. RESULTS: We identified 3972 unique patients who received ECT
      in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000
      inhabitants. Of these patients, 85% opted to participate in the quality register.
      The median age was 55 years (range, 15-94 years), and 63% were women. The
      indication was depression in 78% of the treatment series. Of 4 711 hospitalized
      patients with severe depression, 38% received ECT. The median number of
      treatments per index series was 7. Unilateral treatment was used in 86% of the
      series. CONCLUSIONS: In Sweden, ECT is used at a relatively high rate as compared
      with other western countries, and the rate was unchanged from the last survey in
      1975. However, there is room for improvement in the specificity of use and
      availability of ECT for disorders where ECT is considered a first-line treatment.

PMID- 25973771
TI  - Trends of incidence and survival in squamous-cell carcinoma of the anal canal in
      France: a population-based study.
AB  - Data on anal cancer epidemiology are rare. The aim of this study was to report on
      trends of incidence and survival for anal cancer in France before the
      implementation of the human papilloma virus vaccine. This analysis was carried
      out on 1150 squamous-cell carcinomas of the anal canal diagnosed from 1989 to
      2004 in a population of 5.7 million people covered by eight population-based
      cancer registries. Time trends in incidence were modeled using an age-period
      cohort model. Net survival rates were obtained using the recently validated
      unbiased Pohar-Perme estimator. The incidence of squamous-cell carcinoma of the
      anal canal increased from 0.2 to 0.5/100 000 person-years among men and from 0.7
      to 1.3/100 000 person-years among women from 1982 to 2012. Among women, the
      increase peaked after 2005, with an annual percentage change of +3.4% between
      2005 and 2012, as compared with +2.6% among men. The net survival was 56% (95%
      confidence interval, 49-64) at 5 years and 48% (33-70) at 10 years among men. It
      was higher among women, at 65% (61-69) and 56% (50-63) at 5 and 10 years,
      respectively. The prognosis improved between 1989-1997 and 1998-2004. This
      improvement was slightly greater for men than for women, thus progressively
      reducing the gap between sexes. The incidence of squamous-cell anal canal cancer
      increased slightly among both sexes, but the increase was more marked among women
      than among men. The potential benefit of prophylactic female human papilloma
      virus vaccination against cervical cancer in France should be further evaluated. 

PMID- 25973772
TI  - Emotional specificities of autobiographical memory after breast cancer diagnosis.
AB  - Cancer involves stressful events. One aspect of cognition that is impacted by
      stress is episodic autobiographical memory (EAM). EAM is intimately linked to
      self-representation. Some studies have revealed impairment of EAM in patients
      with breast cancer in remission. Yet, these studies failed to differentiate
      between the influence of adjuvant treatments and that of psychosocial factors. We
      therefore assessed the psychological impact of breast cancer diagnosis on EAM and
      self-representation profiles prior to any adjuvant treatment. Patients newly
      diagnosed with breast cancer (n=31) and women without any history of cancer
      (n=49) were compared on state anxiety, EAM and its emotional characteristics, and
      self-representations. The most anxious patients retrieved fewer emotional details
      for memories than the controls, and had lower self-representation scores than the
      least anxious patients, who had no deficits in emotional detail retrieval. Our
      results revealed distinct EAM profiles for patients, reflecting two contrasting
      modes of coping with breast cancer. 

PMID- 25973773
TI  - Prior expectations facilitate metacognition for perceptual decision.
AB  - The influential framework of 'predictive processing' suggests that prior
      probabilistic expectations influence, or even constitute, perceptual contents.
      This notion is evidenced by the facilitation of low-level perceptual processing
      by expectations. However, whether expectations can facilitate high-level
      components of perception remains unclear. We addressed this question by
      considering the influence of expectations on perceptual metacognition. To isolate
      the effects of expectation from those of attention we used a novel factorial
      design: expectation was manipulated by changing the probability that a Gabor
      target would be presented; attention was manipulated by instructing participants
      to perform or ignore a concurrent visual search task. We found that,
      independently of attention, metacognition improved when yes/no responses were
      congruent with expectations of target presence/absence. Results were modeled
      under a novel Bayesian signal detection theoretic framework which integrates
      bottom-up signal propagation with top-down influences, to provide a unified
      description of the mechanisms underlying perceptual decision and metacognition. 

PMID- 25973774
TI  - Reducing falls and improving mobility in multiple sclerosis.
AB  - Falls are common in persons with multiple sclerosis (MS), and are related to
      physical injury and reduce the quality of life. Mobility impairments are a
      significant risk factor for falls in persons with MS. Although there is evidence
      that mobility in persons with MS can be improved with rehabilitation, much less
      is known about fall prevention. This review focuses on fall prevention in persons
      with MS. Ten fall prevention interventions consisting of 524 participants with a
      wide range of disability were systematically identified. Nine of the 10
      investigations report a reduction in falls and/or proportion of fallers following
      treatment. The vast majority observed an improvement in balance that co-occurred
      with the reduction in falls. Methodological limitations preclude any firm
      conclusions. Numerous gaps in the understanding of fall prevention in persons
      with MS are discussed. Well-designed randomized control trials targeting mobility
      and falls are warranted. 

PMID- 25973775
TI  - An on-ice measurement approach to analyse the biomechanics of ice hockey skating.
AB  - Skating is a fundamental movement in ice hockey; however little research has been
      conducted within the field of hockey skating biomechanics due to the difficulties
      of on-ice data collection. In this study a novel on-ice measurement approach was
      tested for reliability, and subsequently implemented to investigate the forward
      skating technique, as well as technique differences across skill levels. Nine
      high caliber (High) and nine low caliber (Low) hockey players performed 30 m
      forward skating trials. A 3D accelerometer was mounted to the right skate for the
      purpose of stride detection, with the 2nd and 6th strides defined as acceleration
      and steady-state, respectively. The activity of five lower extremity muscles was
      recorded using surface electromyography. Biaxial electro-goniometers were used to
      quantify hip and knee angles, and in-skate plantar force was measured using
      instrumented insoles. Reliability was assessed with the coefficient of multiple
      correlation, which demonstrated moderate (r>0.65) to excellent (r>0.95) scores
      across selected measured variables. Greater plantar-flexor muscle activity and
      hip extension were evident during acceleration strides, while steady state
      strides exhibited greater knee extensor activity and hip abduction range of
      motion (p<0.05). High caliber exhibited greater hip range of motion and forefoot
      force application (p<0.05). The successful implementation of this on-ice mobile
      measurement approach offers potential for athlete monitoring, biofeedback and
      training advice.

PMID- 25973776
TI  - Smoking behaviors and intentions among adolescents in rural China: the
      application of the Theory of Planned Behavior and the role of social influence.
AB  - INTRODUCTION: This study investigated the associations between the variables of
      the theory of planned behavior (TPB), influence of significant others, and
      smoking intentions and behaviors among adolescents living in rural southern
      China. METHODS: A cross-sectional study was conducted among 2609 students in two
      junior high schools in rural Shantou, Guangdong province, using a self
      administered questionnaire. Logistic regression models were fitted to estimate
      univariate and adjusted odds ratios and corresponding 95% confidence intervals.
      RESULTS: Multivariate analyses showed that having favorable attitudes towards
      smoking on psychological and social aspects, perceived behavioral control, and
      having most friends who were current smokers were significantly associated with
      smoking intentions in the next six months and in the next five years. Having most
      family members who were current smokers was also significantly related to smoking
      intention in the next five years. Having favorable attitudes towards smoking on
      psychological aspect and negative attitudes on physical aspect, perceived support
      from friends on smoking, and having most friends and senior relatives being
      current smokers were significantly associated with increased likelihood of ever
      smoking. Perceived behavioral control and having most friends being current
      smokers were also significantly associated with regular smoking and smoking in
      the past 30days. CONCLUSIONS: Our results suggest that the key constructs of the
      TPB model and friends' smoking behaviors play important roles in accounting for
      smoking intentions and behaviors among a sample of rural Chinese adolescents.

PMID- 25973778
TI  - Short-range order of compressed amorphous GeSe2.
AB  - The structure of amorphous GeSe2 (a-GeSe2) has been studied by means of a
      combination of two-edges X-ray absorption spectroscopy (XAS) and angle-dispersive
      X-ray diffraction under pressures up to about 30 GPa. Multiple-edge XAS data
      analysis of a-GeSe2 at ambient conditions allowed us to reconstruct and compare
      the first-neighbor distribution function with previous results obtained by
      neutron diffraction with isotopic substitution. GeSe2 is found to remain
      amorphous up to the highest pressures attained, and a reversible 1.5 eV red-shift
      of the Ge K-edge energy indicating metallization, occurs between 10 GPa and 15
      GPa. Two compression stages are identified by XAS structure refinement. First, a
      decrease of the first-neighbor distances up to about 10 GPa, in the same pressure
      region of a previously observed breakdown of the intermediate-range order.
      Second, an increase of the Ge-Se distances, bond disorder, and of the
      coordination number. This stage is related to a reversible non-isostructural
      transition involving a gradual conversion from tetra- to octa-hedral geometry
      which is not yet fully completed at 30 GPa. 

PMID- 25973777
TI  - Noninvasive Assessment of Excessive Erythrocytosis as a Screening Method for
      Chronic Mountain Sickness at High Altitude.
AB  - Vyas, Kaetan J., David Danz, Robert H. Gilman, Robert A. Wise, Fabiola Leon
      Velarde, J. Jaime Miranda, and William Checkley. Noninvasive assessment of
      excessive erythrocytosis as a screening method for chronic mountain sickness at
      high altitude. High Alt Med Biol 16:162-168, 2015.--Globally, over 140 million
      people are at risk of developing chronic mountain sickness, a common
      maladaptation to life at high altitude (>2500 meters above sea level). The
      diagnosis is contingent upon the identification of excessive erythrocytosis (EE).
      Current best practices to identify EE require a venous blood draw, which is
      cumbersome for large-scale surveillance. We evaluated two point-of-care
      biomarkers to screen for EE: noninvasive spot-check tests of total hemoglobin and
      oxyhemoglobin saturation (Pronto-7, Masimo Corporation). We conducted paired
      evaluations of total serum hemoglobin from a venous blood draw and noninvasive,
      spot-check testing of total hemoglobin and oxyhemoglobin saturation with the
      Pronto-7 in 382 adults aged >=35 years living in Puno, Peru (3825 meters above
      sea level). We used the Bland-Altman method to measure agreement between the
      noninvasive hemoglobin assessment and the gold standard lab hemoglobin analyzer.
      Mean age was 58.8 years and 47% were male. The Pronto-7 test was unsuccessful in
      21 (5%) participants. Limits of agreement between total hemoglobin measured via
      venous blood draw and the noninvasive, spot-check test ranged from -2.8 g/dL (95%
      CI -3.0 to -2.5) to 2.5 g/dL (95% CI 2.2 to 2.7), with a bias of -0.2 g/dL (95%
      CI -0.3 to -0.02) for the difference between total hemoglobin and noninvasive
      hemoglobin concentrations. Overall, the noninvasive spot-check test of total
      hemoglobin had a better area under the receiver operating characteristic curve
      compared to oxyhemoglobin saturation for the identification of EE as measured by
      a gold standard laboratory hemoglobin analyzer (0.96 vs. 0.82; p<0.001). Best cut
      off values to screen for EE with the Pronto 7 were >=19.9 g/dL in males and
      >=17.5 g/dL in females. At these cut-points, sensitivity and specificity were
      both 92% and 89% for males and females, respectively. A noninvasive, spot-check
      test of total hemoglobin had low bias and high discrimination for the detection
      of EE in high altitude Peru, and may be a useful point-of-care tool for large
      scale surveillance in high-altitude settings.

PMID- 25973779
TI  - Predicting the unpredictable: Recent structure-activity studies on peptide-based
      macrocycles.
AB  - Heterocycle-containing macrocycles are an emerging class of molecules that have
      therapeutic efficacy. Many biologically active natural products that have
      interesting biological properties fall into this class of molecules. The highly
      specific and selective biological activity is often attributed to the unique
      conformation of these macrocycles, which is affected by the elements of the
      macrocycles as well as its surroundings in biological systems. In this review,
      the structure-activity relationship studies of several recently developed
      biologically active heterocycle-containing macrocycles have been discussed in
      order to facilitate an understanding on how unpredictable structures can be
      controlled. 

PMID- 25973780
TI  - Microstrip technique in follicular unit extraction.

PMID- 25973781
TI  - Achieving high energy absorption capacity in cellular bulk metallic glasses.
AB  - Cellular bulk metallic glasses (BMGs) have exhibited excellent energy-absorption
      performance by inheriting superior strength from the parent BMGs. However, how to
      achieve high energy absorption capacity in cellular BMGs is vital but mysterious.
      In this work, using step-by-step observations of the deformation evolution of a
      series of cellular BMGs, the underlying mechanisms for the remarkable energy
      absorption capacity have been investigated by studying two influencing key
      factors: the peak stress and the decay of the peak stress during the plastic-flow
      plateau stages. An analytical model of the peak stress has been proposed, and the
      predicted results agree well with the experimental data. The decay of the peak
      stress has been attributed to the geometry change of the macroscopic cells, the
      formation of shear bands in the middle of the struts, and the "work-softening"
      nature of BMGs. The influencing factors such as the effect of the strut thickness
      and the number of unit cells have also been investigated and discussed.
      Strategies for achieving higher energy absorption capacity in cellular BMGs have
      been proposed. 

PMID- 25973782
TI  - Adjuvant treatments of breast cancer increase the risk of depressive disorders: A
      population-based study.
AB  - BACKGROUND: Previous studies have posited conflicting results regarding
      depressive disorders among breast cancer survivors who received adjuvant
      therapies including chemotherapy, radiotherapy, selective estrogen receptor
      modulator (e.g. tamoxifen), third-generation aromatase inhibitors (AIs; e.g.
      anastrozole, letrozole or exemestane), and monoclonal antibody (e.g.
      trastuzumab). We therefore performed a population-based study with a defined
      breast cancer cohort to investigate the risk of depressive disorders in breast
      cancer patients who received adjuvant therapies. METHODS: We conducted a
      retrospective study of a breast cancer cohort of 36,586 participants who were
      selected from the National Health Insurance Research Database(NHIRD) in Taiwan.
      Patients were observed for a maximum of 6 years to determine the incidences of
      newly onset depressive disorders. Kaplan-Meier and Cox regression analyses were
      used to identify the risk factors associated with depressive disorders in breast
      cancer patients who underwent adjuvant therapies RESULTS: Of the total 36,586
      patients, 1342 (3.7%) were ascertained with depressive disorders. The Cox
      multivariate proportional hazards analysis showed that age of 40-59 (adjusted
      hazard ratio (aHR) 1.327, 95% CI 1.123-1.567, p=0.001), chemotherapy (aHR 1.555,
      95% CI 1.387-1.743, p<0.001), radiotherapy (aHR 1.385 95% CI 1.220-1.571,
      p<0.001), tamoxifen (aHR 1.458, 95% CI 1.110-1.914, p=0.007), AIs (aHR 1.360, 95%
      CI 1.193-1.550, p<0.001), and trastuzumab (aHR 1.458, 95% CI 1.110-1.914,
      p=0.007) were independent risk factors for developing depressive disorders.
      LIMITATIONS: The dosage effect of adjuvant treatments, cancer staging, genetic or
      environmental confounders associated with the risk of depressive disorders were
      not comprehensively evaluated. CONCLUSION: Developing depressive disorders are at
      higher risk in breast cancer survivors aged 40-59 who received adjuvant
      treatments including chemotherapy, radiotherapy, tamoxifen, AIs or trastuzumab.
      Psychological evaluation and support are necessarily needed in breast cancer
      survivors who received adjuvant therapies.

PMID- 25973783
TI  - Correlations between amygdala volumes and serum levels of BDNF and NGF as a
      neurobiological markerin adolescents with bipolar disorder.
AB  - BACKGROUND: The amygdala is repeatedly implicated as a critical component of the
      neurocircuitry regulating emotional valence. Studies have frequently reported
      reduced amygdala volumes in children and adolescents with bipolar disorder (BD).
      Brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play
      critical roles in growth, differentiation, maintenance, and synaptic plasticity
      of neuronal systems in adolescent brain development. The aim of the present study
      was to assess amygdala volumesand its correlation with serum levels of NGF and
      BDNF in euthymic adolescents with BD and healthy controls. METHODS: Using
      structural MRI, we compared the amygdala volumes of 30 euthymic subjects with BD
      with 23 healthy control subjects aged between 13 and 19 years during a
      naturalistic clinical follow-up. The boundaries of the amygdala were outlined
      manually. Serum BDNF and NGF levels were measured using sandwich-ELISA and
      compared between the study groups. RESULTS: The right or left amygdala volume did
      not differ between the study groups.The right and left amygdala volumes were
      highly correlated with levels of BDNF in the combined BD group and the valproate
      treated group.Both R and L amygdala volumes were correlated with BDNF levels in
      healthy controls. The left amygdala volumes were correlated with BDNF levels in
      the lithium-treated group. LIMITATIONS: This cross-sectional study cannot inform
      longitudinal changes in brain structure. Further studies with larger sample sizes
      are needed to improve reliability. CONCLUSIONS: The correlations between amygdala
      volumes and BDNF levels might be an early neuromarker for diagnosis and/or
      treatment response in adolescents with BD.

PMID- 25973784
TI  - Predominant polarity in bipolar disorders: Further evidence for the role of
      affective temperaments.
AB  - BACKGROUND: Literature suggests bipolars may differ in several features according
      to predominant polarity, but the role of temperaments remains controversial.
      METHODS: The EPIDEP study was designed to identify bipolar patients among a large
      sample of major depressives. Only bipolars were included in the current study.
      Patients were subtyped as predominantly depressive (PD) and predominantly manic
      and hypomanic (PM) according to a broad (more episodes of a given polarity) and a
      narrow (2/3 of episodes of one polarity over the other) definition, and compared
      on their characteristics. RESULTS: Among 278 bipolars, 182 (79.8%) could be
      subtyped as PD and 46 (20.2%) as PM (broad definition); the respective
      proportions were of 111 (81.6%) and 25 (18.4%) using narrow definition. Expanding
      the definition added little in detecting differences between groups. Compared to
      PDs, PMs showed more psychosis, rapid cycling, stressors at onset, family history
      of affective illness, and manic first episode polarity; they also received more
      antipsychotics and lithium. The PDs showed more chronic depression, comorbid
      anxiety, and received more antidepressants, anticonvulsants and benzodiazepines.
      The following independent variables were associated with manic/hypomanic
      predominant polarity: cyclothymic temperament, first hospitalization<=25 years,
      hyperthymic temperament, and alcohol use (only for broad definition). LIMITATION:
      Cross-sectional design, recall bias. CONCLUSIONS: Study findings are in accord
      with literature except for suicidality and mixicity which were related to
      predominant mania, and explained by higher levels of cyclothymic and hyperthymic
      temperaments. Temperaments may play a key role in the subtyping of bipolar
      patients according to predominant polarity, which warrants confirmation in
      prospective studies.

PMID- 25973785
TI  - Increased serum levels of eotaxin/CCL11 in late-stage patients with bipolar
      disorder: An accelerated aging biomarker?
AB  - BACKGROUND: Bipolar disorder (BD) is commonly comorbid with many medical
      disorders including atopy, and appears characterized by progressive social,
      neurobiological, and functional impairment associated with increasing number of
      episodes and illness duration. Early and late stages of BD may present different
      biological features and may therefore require different treatment strategies.
      Consequently, the aim of this study was to evaluate serum levels of
      eotaxin/CCL11, eotaxin-2/CCL24, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-alpha,
      IFNgamma, BDNF, TBARS, carbonyl, and GPx in a sample of euthymic patients with BD
      at early and late stages compared to controls. METHODS: Early-stage BD patients,
      12 late-stage patients, and 25 controls matched for sex and age were selected.
      10mL of peripheral blood was drawn from all subjects by venipuncture. Serum
      levels of BDNF, TBARS, carbonyl content, glutathione-peroxidase activity (GPx),
      cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-alpha and IFNgamma), and
      chemokines (eotaxin/CCL11 and eotaxin-2/CCL24) were measured. RESULTS: There were
      no demographic differences between patients and controls. No significant
      differences were found for any of the biomarkers, except chemokine eotaxin/CCL11,
      whose serum levels were higher in late-stage patients with BD when compared to
      controls (p=0.022; Mann-Whitney U test). LIMITATIONS: Small number of subjects
      and use of medication may have influenced in our results. CONCLUSION: The present
      study suggests a link between biomarkers of atopy and eosinophil function and
      bipolar disorder. These findings are also in line with progressive biological
      changes partially mediated by inflammatory imbalance, a process referred to as
      neuroprogression.

PMID- 25973786
TI  - High-resolution CMOS MEA platform to study neurons at subcellular, cellular, and
      network levels.
AB  - Studies on information processing and learning properties of neuronal networks
      would benefit from simultaneous and parallel access to the activity of a large
      fraction of all neurons in such networks. Here, we present a CMOS-based device,
      capable of simultaneously recording the electrical activity of over a thousand
      cells in in vitro neuronal networks. The device provides sufficiently high
      spatiotemporal resolution to enable, at the same time, access to neuronal
      preparations on subcellular, cellular, and network level. The key feature is a
      rapidly reconfigurable array of 26 400 microelectrodes arranged at low pitch
      (17.5 MUm) within a large overall sensing area (3.85 * 2.10 mm(2)). An arbitrary
      subset of the electrodes can be simultaneously connected to 1024 low-noise
      readout channels as well as 32 stimulation units. Each electrode or electrode
      subset can be used to electrically stimulate or record the signals of virtually
      any neuron on the array. We demonstrate the applicability and potential of this
      device for various different experimental paradigms: large-scale recordings from
      whole networks of neurons as well as investigations of axonal properties of
      individual neurons. 

PMID- 25973787
TI  - Protection against Influenza A Virus Challenge with M2e-Displaying Filamentous
      Escherichia coli Phages.
AB  - Human influenza viruses are responsible for annual epidemics and occasional
      pandemics that cause severe illness and mortality in all age groups worldwide.
      Matrix protein 2 (M2) of influenza A virus is a tetrameric type III membrane
      protein that functions as a proton-selective channel. The extracellular domain of
      M2 (M2e) is conserved in human and avian influenza A viruses and is being pursued
      as a component for a universal influenza A vaccine. To develop a M2e vaccine that
      is economical and easy to purify, we genetically fused M2e amino acids 2-16 to
      the N-terminus of pVIII, the major coat protein of filamentous bacteriophage f88.
      We show that the resulting recombinant f88-M2e2-16 phages are replication
      competent and display the introduced part of M2e on the phage surface.
      Immunization of mice with purified f88-M2e2-16 phages in the presence of
      incomplete Freund's adjuvant, induced robust M2e-specific serum IgG and protected
      BALB/c mice against challenge with human and avian influenza A viruses. Thus,
      replication competent filamentous bacteriophages can be used as efficient and
      economical carriers to display conserved B cell epitopes of influenza A. 

PMID- 25973788
TI  - Humour processing in frontotemporal lobar degeneration: A behavioural and
      neuroanatomical analysis.
AB  - Humour is a complex cognitive and emotional construct that is vulnerable in
      neurodegenerative diseases, notably the frontotemporal lobar degenerations.
      However, humour processing in these diseases has been little studied. Here we
      assessed humour processing in patients with behavioural variant frontotemporal
      dementia (n = 22, mean age 67 years, four female) and semantic dementia (n = 11,
      mean age 67 years, five female) relative to healthy individuals (n = 21, mean age
      66 years, 11 female), using a joint cognitive and neuroanatomical approach. We
      created a novel neuropsychological test requiring a decision about the humorous
      intent of nonverbal cartoons, in which we manipulated orthogonally humour content
      and familiarity of depicted scenarios. Structural neuroanatomical correlates of
      humour detection were assessed using voxel-based morphometry. Assessing
      performance in a signal detection framework and after adjusting for standard
      measures of cognitive function, both patient groups showed impaired accuracy of
      humour detection in familiar and novel scenarios relative to healthy older
      controls (p < .001). Patient groups showed similar overall performance profiles;
      however the behavioural variant frontotemporal dementia group alone showed a
      significant advantage for detection of humour in familiar relative to novel
      scenarios (p = .045), suggesting that the behavioural variant syndrome may lead
      to particular difficulty decoding novel situations for humour, while semantic
      dementia produces a more general deficit of humour detection that extends to
      stock comedic situations. Humour detection accuracy was associated with grey
      matter volume in a distributed network including temporo-parietal junctional and
      anterior superior temporal cortices, with predominantly left-sided correlates of
      processing humour in familiar scenarios and right-sided correlates of processing
      novel humour. The findings quantify deficits of core cognitive operations
      underpinning humour processing in frontotemporal lobar degenerations and suggest
      a candidate brain substrate in cortical hub regions processing incongruity and
      semantic associations. Humour is a promising candidate tool with which to assess
      complex social signal processing in neurodegenerative disease. 

PMID- 25973789
TI  - Alternative NF-kappaB signaling regulates mTEC differentiation from podoplanin
      expressing precursors in the cortico-medullary junction.
AB  - The thymic epithelium forms specialized niches to enable thymocyte
      differentiation. While the common epithelial progenitor of medullary and cortical
      thymic epithelial cells (mTECs and cTECs) is well defined, early stages of mTEC
      lineage specification have remained elusive. Here, we utilized in vivo targeting
      of mTECs to resolve their differentiation pathways and to determine whether mTEC
      progenitors participate in thymocyte education. We found that mTECs descend from
      a lineage committed, podoplanin (PDPN)-expressing progenitor located at the
      cortico-medullary junction. PDPN(+) junctional TECs (jTECs) represent a distinct
      TEC population that builds the thymic medulla, but only partially supports
      negative selection and thymocyte differentiation. Moreover, conditional gene
      targeting revealed that abrogation of alternative NF-kappaB pathway signaling in
      the jTEC stage completely blocked mTEC development. Taken together, this study
      identifies jTECs as lineage-committed mTEC progenitors and shows that NF-kappaB
      dependent progression of jTECs to mTECs is critical to secure central tolerance.

PMID- 25973790
TI  - Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the
      Optimization of the Osteoblastic Niche.
AB  - We previously reported a new approach for culturing difficult-to-preserve primary
      patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D
      tissue scaffold constructed in a perfused microfluidic environment and a culture
      medium supplemented with patient plasma. In the current study, we used this
      biomimetic model to show, for the first time, that the long-term survival of OSB
      is the most critical factor in maintaining the ex vivo viability and
      proliferative capacity of MMC. We found that the adhesion and retention of MMC to
      the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential
      mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC
      and patient plasma, the viability and osteogenic activity of OSB became gradually
      compromised, and consequently MMC could not remain viable over 3 weeks. We
      demonstrated that the long-term survival of both OSB and MMC could be enhanced
      by: (1) optimizing perfusion flow rate and patient-derived plasma composition in
      the culture medium and (2) replenishing OSB during culture as a practical means
      of prolonging MMC's viability beyond several weeks. These findings were obtained
      using a high-throughput well plate-based perfusion device from the perspective of
      optimizing the ex vivo preservation of patient-derived MM biospecimens for
      downstream use in biological studies and chemosensitivity analyses. 

PMID- 25973791
TI  - Identification of Sestrin3 Involved in the In vitro Resistance of Colorectal
      Cancer Cells to Irinotecan.
AB  - Irinotecan, an analogue of camptothecin, is frequently used as a single agent or
      in combination with other anticancer drugs for the treatment of colorectal
      cancer. However, the drug resistance of tumors is a major obstacle to successful
      cancer treatment. In this study, we established that cells acquire chronic
      resistance to irinotecan. We profiled their differential gene expression using
      microarray. After gene ontology (GO) and KEGG pathway analysis of the microarray
      data, we specifically investigated whether Sestrin3 could decrease irinotecan
      resistance. Our results revealed that Sestrin3 enhanced the anticancer effect of
      irinotecan in vitro in LoVo cells that had acquired resistance to irinotecan.
      Irinotecan-resistant LoVo cells showed lower reactive oxygen species (ROS)
      production than their irinotecan-sensitive parental cells. ROS production was
      increased by Sestrin3 knockdown in irinotecan-resistant LoVo cells. Our results
      indicate that Sestrin3 might be a good target to develop therapeutics that can
      help to overcome resistance to irinotecan. 

PMID- 25973792
TI  - Permeation of proteins, oligonucleotide and dextrans across ocular tissues:
      experimental studies and a literature update.
AB  - Proteins and oligonucleotides represent powerful tools for the treatment of
      several ocular diseases, affecting both anterior and posterior eye segments.
      Despite the potential of these compounds, their administration remains a
      challenge. The last years have seen a growing interest for the noninvasive
      administration of macromolecular drugs, but still there is only little
      information of their permeability across the different ocular barriers. The aim
      of this work was to evaluate the permeation of macromolecules of different size,
      shape and charge across porcine ocular tissues such as the isolated sclera, the
      choroid Bruch's membrane and the cornea, both intact and de-epitelialized.
      Permeants used were two proteins (albumin and cytochrome C), an oligonucleotide,
      two dextrans (4 and 40 kDa) and a monoclonal antibody (bevacizumab). Obtained
      data and its comparison with the literature highlight the difficulties in
      predicting the behavior of macromolecules based on their physicochemical
      properties, because the interplay between the charge, molecular radius and
      conformation prevent their analysis separately. However, the data can be of great
      help for a rough evaluation of the feasibility of a noninvasive administration
      and for building computational models to improve understanding of the interplay
      among static, dynamic and metabolic barriers in the delivery of macromolecules to
      the eye.

PMID- 25973793
TI  - Pharmacology, Efficacy and Safety of Felodipine with a Focus on Hypertension and
      Angina Pectoris.
AB  - Calcium channel blockers (CCBs) are a heterogeneous group of drugs often used in
      the therapy for hypertension and angina. Though CCBs are generally similar in
      terms of their efficacy yet, they differ in their ability of causing selective
      inhibition in the contractility of vascular smooth muscle in comparison to
      cardiac muscle. Felodipine is one of the most vascular selective of the available
      CCBs and it has no negative inotropic effects at clinically administered doses.
      Focus of this review is to comprehensively summarize the pharmacokinetics,
      efficacy, safety and tolerability of felodipine. This review is based on
      evaluation of relevant literature on felodipine using meta-database PubMed and
      ScienceDirect and internet search engine (Google Scholar). Clinical studies
      summarized in this review testify, on technical lines, the clinical efficacy,
      safety and placebo- like tolerability profile of felodipine, administered alone
      as well as in combination. 

PMID- 25973794
TI  - Francisella tularensis Vaccines Elicit Concurrent Protective T- and B-Cell Immune
      Responses in BALB/cByJ Mice.
AB  - In the last decade several new vaccines against Francisella tularensis, which
      causes tularemia, have been characterized in animal models. Whereas many of these
      vaccine candidates showed promise, it remains critical to bridge the preclinical
      studies to human subjects, ideally by taking advantage of correlates of
      protection. By combining in vitro intramacrophage LVS replication with gene
      expression data through multivariate analysis, we previously identified and
      quantified correlative T cell immune responses that discriminate vaccines of
      different efficacy. Further, using C57BL/6J mice, we demonstrated that the
      relative levels of gene expression vary according to vaccination route and
      between cell types from different organs. Here, we extended our studies to the
      analysis of T cell functions of BALB/cByJ mice to evaluate whether our approach
      to identify correlates of protection also applies to a Th2 dominant mouse strain.
      BALB/cByJ mice had higher survival rates than C57BL/6J mice when they were
      immunized with suboptimal vaccines and challenged. However, splenocytes derived
      from differentially vaccinated BALB/cByJ mice controlled LVS intramacrophage
      replication in vitro in a pattern that reflected the hierarchy of protection
      observed in C57BL/6J mice. In addition, gene expression of selected potential
      correlates revealed similar patterns in splenocytes of BALB/cByJ and C57BL/6J
      mice. The different survival patterns were related to B cell functions, not
      necessarily to specific antibody production, which played an important protective
      role in BALB/cByJ mice when vaccinated with suboptimal vaccines. Our studies
      therefore demonstrate the range of mechanisms that operate in the most common
      mouse strains used for characterization of vaccines against F. tularensis, and
      illustrate the complexity necessary to define a comprehensive set of correlates. 

PMID- 25973795
TI  - Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO
      Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin.
AB  - BACKGROUND: Rupture of an atherosclerotic plaque is the primary cause of acute
      cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of
      vulnerable atherosclerotic plaques (VP) would be significant in preventing some
      aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid
      (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized
      and used to identify VP and rupture plaque by magnetic resonance imaging (MRI).
      METHODS: Atherosclerosis was induced in male New Zealand White rabbits by feeding
      a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10)
      were controls. VP was established in groups B (n = 10) and C (n = 10) using
      balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying
      p53 genes were injected into the aortic segments rich in plaques after 8 weeks.
      Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all
      rabbits underwent pharmacological triggering, and imaging were taken daily for 5
      d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP
      9, sCD40L, and other lipid indicators were measured. RESULTS: DMSA-USPIO
      particles accumulated in VP and rupture plaques. Rupture plaques appeared as
      areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted
      sequences, with a signal strength peaking at 96 h. The group given atorvastatin
      showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9
      and sCD40L levels in group B were significantly higher than in the other 2 groups
      (P <0.05). CONCLUSION: After successfully establishing a VP model in rabbits,
      DMSA-USPIO was used to enhance MRI for clear identification of plaque
      inflammation and rupture. Rupture plaques were detectable in this way probably
      due to an activating inflammatory process. Atorvastatin reduced the inflammatory
      response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.

PMID- 25973796
TI  - Yeast killer elements hold their hosts hostage.

PMID- 25973797
TI  - Women with nonobstructive coronary artery disease are not necessarily healthy.

PMID- 25973798
TI  - Addressing the Intersection of HIV and Intimate Partner Violence Among Women with
      or at Risk for HIV in the United States.
AB  - In 2012, the White House established a working group in recognition of the need
      to understand and address the intersection of human immunodeficiency virus (HIV)
      infection and violence against women and girls. This report describes the Centers
      for Disease Control and Prevention (CDC)'s efforts for addressing intimate
      partner violence and HIV among women and provides suggestions for future
      prevention efforts. CDC's current efforts are focused on understanding these
      often co-occurring public health problems, identifying effective interventions,
      and ensuring that states and communities have the capacity and resources to
      implement prevention approaches based on the best available evidence. Additional
      research is needed on effective strategies for integrating violence prevention
      and HIV programming into health services targeting adolescent girls and women who
      experience intimate partner violence or are at risk for HIV. 

PMID- 25973799
TI  - The impact of multimorbidity on quality of life among midlife women: findings
      from a U.S. nationally representative survey.
AB  - BACKGROUND: Little is known about the prevalence and cumulative burden of
      coexisting health conditions including chronic joint and muscular pain, urinary
      incontinence (UI), depression, osteoporosis risk, moderate/severe vasomotor
      symptoms, and vulvar/vaginal atrophy (VVA). We surveyed a nationally
      representative U.S. sample of midlife (age 40-64 years) women to ascertain the
      prevalence, general health-related quality of life (HRQoL), and health-seeking
      behaviors associated with these six conditions. METHODS: This cross-sectional,
      telephone survey collected data from a sample of English- and Spanish-speaking
      U.S. women. The survey contained demographic and menopausal status questions, and
      also five condition-specific symptom/disease risk-screening instruments. The
      EuroQol 5 dimensions (EQ-5D) questionnaire was used to measure HRQoL. Health
      seeking behavior was measured based on clinician discussion of and recent
      treatment for each condition. RESULTS: Three thousand fifty eight women (mean age
      53.4 years) completed the survey. The majority were white (75.6%), married
      (60.5%), employed full- or part-time (59.0%), and postmenopausal (69.8%; based on
      self-report). The prevalence [95% confidence interval] of 0, 1, 2, and >=3
      conditions was 35.2% [33.5-36.9], 34.2% [32.5-35.9], 17.9% [16.6-19.3], and 12.7%
      [11.5-13.9], respectively. Osteoporosis risk (30.6%) was most prevalent, followed
      by VVA (27.8%) and UI (26.6%). UI and VVA coexisted most frequently (11.3%),
      followed by osteoporosis risk and VVA (9.8%). EQ-5D scores decreased with
      increasing number of illnesses (0, 1, 2, and >=3 conditions, means: 0.92, 0.87,
      0.77, 0.61, respectively; p<0.01). Health-seeking behavior varied by condition.
      CONCLUSION: Over 25% of women surveyed had multiple coexisting conditions. Lower
      HRQoL was associated with multiple conditions and with each added condition.

PMID- 25973800
TI  - Substitutes for breastmilk--weighing the risks.

PMID- 25973801
TI  - Nitric oxide and Brazilian propolis combined accelerates tissue repair by
      modulating cell migration, cytokine production and collagen deposition in
      experimental leishmaniasis.
AB  - The fact that drugs currently used in the treatment of Leishmania are highly
      toxic and associated with acquired resistance has promoted the search for new
      therapies for treating American tegumentary leishmaniasis (ATL). In this study,
      BALB/c mice were injected in the hind paw with Leishmania (Leishmania)
      amazonensis and subsequently treated with a combination of nitric oxide (NO)
      donor (cis-[Ru(bpy) 2imN(NO)](PF6)3) (Ru-NO), given by intraperitoneal injection,
      and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion
      and increased the NO level in the injured hind paw without lesion exacerbation.
      Histological and immunological parameters of chronic inflammation showed that
      this combined treatment increased the efficacy of macrophages, determined by the
      decrease in the number of parasitized cells, leading to reduced expression of
      proinflammatory and tissue damage markers. In addition, these drugs in
      combination fostered wound healing, enhanced the number of fibroblasts, pro
      healing cytokines and induced collagen synthesis at the lesion site. Overall, our
      findings suggest that the combination of the NO donor Ru-NO and Brazilian
      propolis alleviates experimental ATL lesions, highlighting a new therapeutic
      option that can be considered for further in vivo investigations as a candidate
      for the treatment of cutaneous leishmaniasis. 

PMID- 25973803
TI  - School Start Time and Adolescent Sleep Patterns: Results From the U.S. National
      Comorbidity Survey--Adolescent Supplement.
AB  - OBJECTIVES: We estimated associations between school start time and adolescent
      weeknight bedtime, weeknight sleep duration, and weekend compensatory sleep and
      assessed whether associations differ by age, sex, or urbanicity. METHODS: We used
      a subsample of a nationally representative, cross-sectional survey of 7308
      students aged 13 to 18 years attending 245 schools to estimate associations of
      school start time, reported by school principals, with weeknight bedtime and
      sleep duration and weekend compensatory sleep, reported during adolescent face-to
      face interviews. RESULTS: Start time was positively associated with weeknight
      bedtime. Associations between start time and weeknight sleep duration were
      nonlinear and were strongest for start times of 8:00 am and earlier. Associations
      differed by sex and urbanicity, with the strongest association among boys in
      major metropolitan counties. Start time was negatively associated with sleep
      duration among boys in nonurban counties. Start time was not associated with
      weekend compensatory sleep. CONCLUSIONS: Positive overall associations between
      school start time and adolescent sleep duration at the national level support
      recent policy recommendations for delaying school start times. However, the
      impact of start time delays may differ by sex and urbanicity.

PMID- 25973802
TI  - Multiple Service System Involvement and Later Offending Behavior: Implications
      for Prevention and Early Intervention.
AB  - OBJECTIVES: We investigated patterns of childhood and adolescent experiences that
      correspond to later justice system entry, including persistence into adulthood,
      and explored whether timing of potential supports to the child or onset of family
      poverty, according to developmental periods and gender, would distinguish among
      latent classes. METHODS: We constructed a database containing records for 8587
      youths from a Midwestern metropolitan region, born between 1982 and 1991, with
      outcomes. We used data from multiple publicly funded systems (child welfare,
      income maintenance, juvenile and criminal justice, mental health, Medicaid, vital
      statistics). We applied a latent class analysis and interpreted a 7-class model.
      RESULTS: Classes with higher rates of offending persisting into adulthood were
      characterized by involvement with multiple publicly funded systems in childhood
      and adolescence, with the exception of 1 less-urban, predominantly female class
      that had similarly high system involvement coupled with lower rates of offending.
      CONCLUSIONS: Poverty and maltreatment appear to play a critical role in offending
      trajectories. Identifying risk factors that cluster together may help program and
      intervention staff best target those most in need of more intensive intervention.

PMID- 25973804
TI  - Behavioral Health Care Needs, Detention-Based Care, and Criminal Recidivism at
      Community Reentry From Juvenile Detention: A Multisite Survival Curve Analysis.
AB  - OBJECTIVES: We examined the provision of behavioral health services to youths
      detained in Indiana between 2008 and 2012 and the impact of services on
      recidivism. METHOD: We obtained information about behavioral health needs,
      behavioral health treatment received, and recidivism within 12 months after
      release for 8363 adolescents (aged 12-18 years; 79.4% male). We conducted
      survival analyses to determine whether behavioral health services significantly
      affected time to recidivating. RESULTS: Approximately 19.1% of youths had
      positive mental health screens, and 25.3% of all youths recidivated within 12
      months after release. Of youths with positive screens, 29.2% saw a mental health
      clinician, 16.1% received behavioral health services during detention, and 30.0%
      received referrals for postdetention services. Survival analyses showed that
      being male, Black, and younger, and having higher scores on the substance use or
      irritability subscales of the screen predicted shorter time to recidivism.
      Receiving a behavior precaution, behavioral health services in detention, or an
      assessment in the community also predicted shorter time to recidivating.
      CONCLUSIONS: Findings support previous research showing that behavioral health
      problems are related to recidivism and that Black males are disproportionately
      rearrested after detention.

PMID- 25973805
TI  - Suicide Risk in Nursing Homes and Assisted Living Facilities: 2003-2011.
AB  - OBJECTIVES: We investigated the epidemiology of suicide among adults aged 50
      years and older in nursing homes and assisted living facilities and whether
      anticipating transitioning into long-term care (LTC) is a risk factor for
      suicide. METHODS: Data come from the Virginia Violent Death Reporting System
      (2003-2011). We matched locations of suicides (n = 3453) against publicly
      available resource registries of nursing homes (n = 285) and assisted living
      facilities (n = 548). We examined individual and organizational correlates of
      suicide by logistic regression. We identified decedents anticipating entry into
      LTC through qualitative text analysis. RESULTS: Incidence of suicide was 14.16
      per 100 000 in nursing homes and 15.66 in the community. Better performance on
      Nursing Home Compare quality metrics was associated with higher odds of suicide
      in nursing homes (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.21,
      3.14). Larger facility size was associated with higher suicide risk in assisted
      living facilities (OR = 1.01; 95% CI = 1.00, 1.01). Text narratives identified 38
      decedents anticipating transitioning into LTC and 16 whose loved one recently
      transitioned or resided in LTC. CONCLUSIONS: LTC may be an important point of
      engagement in suicide prevention.

PMID- 25973806
TI  - Cautionary Notes on a Global Tiered Pricing Framework for Medicines.
AB  - Recently, there has been a policy momentum toward creating a global tiered
      pricing framework, which would provide differentiated prices for medicines
      globally, based on each country's capacity to pay. We studied the most
      influential proposals for a tiered pricing framework since the 1995 World Trade
      Organization's Agreement on Trade-Related Aspects of Intellectual Property
      Rights. We synthesized 6 critical questions to be addressed for a global
      framework to function and explored the many challenges of implementation.
      Although we acknowledge that there is the potential for an exceptional global
      commitment that would benefit both producers and those in developing countries in
      need of wider access to medicines, our greatest concern is to ensure that a
      global framework does not price out the poor from pharmaceutical markets nor
      threaten current flexibilities within the international patent regime. 

PMID- 25973807
TI  - Sexual Orientation and Risk of Pregnancy Among New York City High-School
      Students.
AB  - OBJECTIVES: We examined associations between sexual orientation and pregnancy
      risk among sexually experienced New York City high-school students. METHODS: We
      analyzed data from 2005, 2007, and 2009 New York City Youth Risk Behavior
      Surveys. We excluded students who had never engaged in sexual intercourse, only
      had same-gender sexual partners, or had missing data on variables of interest,
      resulting in a final sample of 4892 female and 4811 male students. We employed
      multivariable logistic regression to examine pregnancy risk by sexual
      orientation, measured as self-reported sexual identity and gender of sexual
      partners, with adjustment for demographics and sexual behaviors. We stratified
      analyses by gender. RESULTS: Overall, 14.3% of female and 10.8% of male students
      had experienced a pregnancy. Students who identified as gay, lesbian, or bisexual
      or reported both male and female sexual partners had higher odds of pregnancy
      than heterosexual students or students who only had opposite-gender sexual
      partners. Sexual behaviors accounted for higher odds of pregnancy among female,
      but only partially accounted for higher odds of pregnancy involvement among male,
      sexual-minority students. CONCLUSIONS: Sexual orientation should be considered in
      future adolescent pregnancy-prevention efforts, including the design of pregnancy
      prevention interventions.

PMID- 25973808
TI  - Child Farm Laborers.

PMID- 25973809
TI  - Knowledge Gains Following a Child Sexual Abuse Prevention Program Among Urban
      Students: A Cluster-Randomized Evaluation.
AB  - OBJECTIVES: We evaluated a school-based child sexual abuse (CSA) prevention
      program, Safe Touches, in a low-socioeconomic status, racially diverse sample.
      METHODS: Participants were 492 second- and third-grade students at 6 public
      elementary schools in New York City. The study period spanned fall 2012 through
      summer 2014. We cluster-randomized classrooms to the Safe Touches intervention or
      control groups and assessed outcomes with the Children's Knowledge of Abuse
      Questionnaire. Hierarchical models tested change in children's knowledge of
      inappropriate and appropriate touch. RESULTS: The intervention group showed
      significantly greater improvement than the control group on knowledge of
      inappropriate touch. Children in second grade and children in schools with a
      greater proportion of students in general (vs special) education showed greater
      gains than other participants in knowledge of inappropriate touch. We observed no
      significant change in knowledge of appropriate touch among control or
      intervention groups. CONCLUSIONS: Young children benefited from a school-based, 1
      time CSA prevention program. Future research should explore the efficacy of CSA
      prevention programs with children before the second grade to determine optimal
      age for participation.

PMID- 25973810
TI  - Convenience Sampling of Children Presenting to Hospital-Based Outpatient Clinics
      to Estimate Childhood Obesity Levels in Local Surroundings.
AB  - Childhood obesity is a critical public health matter associated with numerous
      pediatric comorbidities. Local-level data are required to monitor obesity and to
      help administer prevention efforts when and where they are most needed. We
      hypothesized that samples of children visiting hospital clinics could provide
      representative local population estimates of childhood obesity using data from
      2007 to 2013. Such data might provide more accurate, timely, and cost-effective
      obesity estimates than national surveys. Results revealed that our hospital-based
      sample could not serve as a population surrogate. Further research is needed to
      confirm this finding. 

PMID- 25973811
TI  - Realizing Reproductive Health Equity for Adolescents and Young Adults.

PMID- 25973813
TI  - The Unintended Consequences of Changes in Beverage Options and the Removal of
      Bottled Water on a University Campus.
AB  - OBJECTIVES: We investigated how the removal of bottled water along with a minimum
      healthy beverage requirement affected the purchasing behavior, healthiness of
      beverage choices, and consumption of calories and added sugars of university
      campus consumers. METHODS: With shipment data as a proxy, we estimated bottled
      beverage consumption over 3 consecutive semesters: baseline (spring 2012), when a
      30% healthy beverage ratio was enacted (fall 2012), and when bottled water was
      removed (spring 2013) at the University of Vermont. We assessed changes in number
      and type of beverages and per capita calories, total sugars, and added sugars
      shipped. RESULTS: Per capita shipments of bottles, calories, sugars, and added
      sugars increased significantly when bottled water was removed. Shipments of
      healthy beverages declined significantly, whereas shipments of less healthy
      beverages increased significantly. As bottled water sales dropped to zero, sales
      of sugar-free beverages and sugar-sweetened beverages increased. CONCLUSIONS: The
      bottled water ban did not reduce the number of bottles entering the waste stream
      from the university campus, the ultimate goal of the ban. With the removal of
      bottled water, consumers increased their consumption of less healthy bottled
      beverages.

PMID- 25973812
TI  - Regularly Drinking Alcohol Before Sexual Activity in a Nationally Representative
      Sample: Prevalence, Sociodemographics, and Associations With Psychiatric and
      Substance Use Disorders.
AB  - OBJECTIVES: We addressed regular drinking before sex and its associated risk
      factors. METHODS: From the wave 2 National Epidemiologic Survey on Alcohol and
      Related Conditions, a nationally representative adult US sample (fielded 2004
      2005), we determined the 12-month prevalence of regularly drinking alcohol before
      sexual activity. Among 17,491 sexually active drinkers, we determined the
      sociodemographic, psychiatric, and substance use correlates of regularly drinking
      before sex. RESULTS: Regular presex drinking's 12-month prevalence was 1.8%.
      Significant bivariate sociodemographic correlates were age, gender,
      race/ethnicity, education, family income, marital status, and employment status.
      Generalized anxiety disorder and alcohol dependence were associated with
      significantly increased odds of being a regular presex drinker after controlling
      for covariates. CONCLUSIONS: We estimate that 4.3 million American adults are
      regular presex drinkers. Future research should examine this public health issue
      at the population level, with particular focus on pathways that link it to
      psychopathology.

PMID- 25973814
TI  - Sustainability: The Critical Piece in a Successful Intervention.

PMID- 25973815
TI  - Mervyn Susser (1921-2014): Fighter for Social Justice and Pioneer in
      Epidemiology.

PMID- 25973816
TI  - Estimating the Number of Patients Infected With Chronic HCV in the United States
      Who Meet Highest or High-Priority Treatment Criteria.
AB  - We estimated the number of people infected with HCV in the United States who
      would qualify for immediate treatment according to the 2014 guidance. We based
      fibrosis stage on biopsy results, when available, or on FIB-4 scores. We used
      laboratory tests and International Classification of Diseases, Ninth Revision,
      Clinical Modification codes to determine if patients had any qualifying
      comorbidities. Of the 2.7 million people with HCV infection, we assumed that 1.35
      million (50%) had been diagnosed. We estimated 457, 000 met the highest and 356,
      000 the high-priority criteria for treatment, indicating that as many as 813,000
      people could be treated immediately with new therapies. These estimates can
      inform planning efforts to address clinical capacity constraints and treatment
      costs.

PMID- 25973817
TI  - Work Safety Climate, Safety Behaviors, and Occupational Injuries of Youth
      Farmworkers in North Carolina.
AB  - OBJECTIVES: The aims of this project were to describe the work safety climate and
      the association between occupational safety behaviors and injuries among hired
      youth farmworkers in North Carolina (n = 87). METHODS: We conducted personal
      interviews among a cross-sectional sample of youth farmworkers aged 10 to 17
      years. RESULTS: The majority of youths reported that work safety practices were
      very important to management, yet 38% stated that supervisors were only
      interested in "doing the job quickly and cheaply." Few youths reported
      appropriate work safety behavior, and 14% experienced an injury within the past
      12 months. In bivariate analysis, perceptions of work safety climate were
      significantly associated with pesticide exposure risk factors for rewearing wet
      shoes (P = .01), wet clothes (P = .01), and shorts (P = .03). CONCLUSIONS: Youth
      farmworkers perceived their work safety climate as being poor. Although
      additional research is needed to support these findings, these results strengthen
      the need to increase employer awareness to improve the safety climate for
      protecting youth farmworkers from harmful exposures and injuries.

PMID- 25973819
TI  - Washington and Welch Talk About Race Public Health, History, and the Politics of
      Exclusion.
AB  - This article shows how history can be used as a tool to influence political
      debate. Public health education over the radio became remarkably popular in the
      United States in the years leading up to World War II. Lectures, monologues,
      round tables, question and answer sessions, and dramas were all used by health
      departments to communicate ideas and knowledge about preserving health. In
      Baltimore, Maryland, a radio series called Keeping Well began in 1932 and ran
      until 1957. From 1939, 15-minute weekly dramas were broadcast that adopted many
      of the tropes of contemporary entertainment programs. Some of these dramas were
      based on interpretations of past events and imposed a particular kind of
      narrative of medical and social progress that reflected the wider purpose of
      educational radio programming to uplift and reform listeners. This article
      demonstrates how public health administrators manipulated historical narratives
      and fictionalized history for their own purposes. This manipulation was
      particularly evident in regard to divisive issues such as residential
      segregation, whereby the public health dramas downplayed Baltimore's troubled
      encounter with race and health. 

PMID- 25973818
TI  - The HIV Care Cascade Before, During, and After Incarceration: A Systematic Review
      and Data Synthesis.
AB  - We conducted a systematic literature review of the data on HIV testing,
      engagement in care, and treatment in incarcerated persons, and estimated the care
      cascade in this group. We identified 2706 titles in MEDLINE, EBSCO, and Cochrane
      Library databases for studies indexed to January 13, 2015, and included 92 for
      analysis. We summarized HIV testing results by type (blinded, opt-out,
      voluntary); reviewed studies on HIV care engagement, treatment, and virological
      suppression; and synthesized these results into an HIV care cascade before,
      during, and after incarceration. The HIV care cascade following diagnosis
      increased during incarceration and declined substantially after release, often to
      levels lower than before incarceration. Incarceration provides an opportunity to
      address HIV care in hard-to-reach individuals, though new interventions are
      needed to improve postrelease care continuity. 

PMID- 25973820
TI  - Determinants of First-Time Cancer Examinations in a Rural Community: A Mechanism
      for Behavior Change.
AB  - OBJECTIVES: After conducting a media campaign focusing on the importance of oral
      and pharyngeal cancer (OPC) examinations, we assessed mechanisms of behavior
      change among individuals receiving an OPC examination for the first time.
      METHODS: We used data from 2 waves of telephone surveys of individuals residing
      in 36 rural census tracts in northern Florida (n = 806). The second survey
      occurred after our media intervention. We developed media messages and modes of
      message delivery with community members via focus groups and intercept
      interviews. We performed a mediation analysis to examine behavior change
      mechanisms. RESULTS: Greater exposure to media messages corresponded with
      heightened concern about OPC. Heightened concern, in turn, predicted receipt of a
      first-time OPC examination, but only among men. CONCLUSIONS: We extended earlier
      studies by measuring an outcome behavior (receipt of an OPC examination) and
      demonstrating that the putative mechanism of action (concern about the disease)
      explained the link between a media intervention and engaging in the target
      behavior. Improving the quality of media campaigns by engaging community
      stakeholders in selecting messages and delivery methods is an effective strategy
      in building public health interventions aimed at changing behaviors.

PMID- 25973821
TI  - Starr Responds.

PMID- 25973823
TI  - Acharya et al. Respond.

PMID- 25973824
TI  - Regarding the Regulation of Dietary Supplements.

PMID- 25973822
TI  - Health Outcomes of Obtaining Housing Among Older Homeless Adults.
AB  - OBJECTIVES: We determined the impact of obtaining housing on geriatric conditions
      and acute care utilization among older homeless adults. METHODS: We conducted a
      12-month prospective cohort study of 250 older homeless adults recruited from
      shelters in Boston, Massachusetts, between January and June 2010. We determined
      housing status at follow-up, determined number of emergency department visits and
      hospitalizations over 12 months, and examined 4 measures of geriatric conditions
      at baseline and 12 months. Using multivariable regression models, we evaluated
      the association between obtaining housing and our outcomes of interest. RESULTS:
      At 12-month follow-up, 41% of participants had obtained housing. Compared with
      participants who remained homeless, those with housing had fewer depressive
      symptoms. Other measures of health status did not differ by housing status.
      Participants who obtained housing had a lower rate of acute care use, with an
      adjusted annualized rate of acute care visits of 2.5 per year among participants
      who obtained housing and 5.3 per year among participants who remained homeless.
      CONCLUSIONS: Older homeless adults who obtained housing experienced improved
      depressive symptoms and reduced acute care utilization compared with those who
      remained homeless.

PMID- 25973825
TI  - The Impact of Weather on Mobility and Participation in Older U.S. Adults.
AB  - OBJECTIVES: We examined the impact of weather on the daily lives of US adults to
      understand which populations are most vulnerable to various weather conditions.
      METHODS: Data came from a 2013 supplement to the University of Michigan-Thomson
      Reuters Surveys of Consumers, a nationally representative telephone survey of 502
      adults in the contiguous United States. We used logistic regressions to assess
      the odds of mobility difficulty and participation restriction during different
      weather conditions, as well as age group differences. RESULTS: Ice was most
      likely to change the way respondents got around (reported by 47%). In icy
      conditions, participants had difficulty leaving home (40%) and driving (35%).
      Facing ice, older adults (>= 65 years) had twice the odds of having great
      difficulty leaving home (odds ratio [OR] = 2.22; 95% confidence interval [CI] =
      1.12, 4.42) and curtailing work or volunteer activities (OR = 2.01; 95% CI =
      1.01, 4.06), and 3 times the odds of difficulty driving (OR = 3.33; 95% CI =
      1.62, 6.86) as younger respondents. We also found significant differences in
      mobility and participation by gender and region of residence. CONCLUSIONS:
      Weather can affect social isolation, health, well-being, and mortality among
      older US adults.

PMID- 25973826
TI  - Sedentary Behavior as a Risk Factor for Physical Frailty Independent of Moderate
      Activity: Results From the Osteoarthritis Initiative.
AB  - OBJECTIVES: This prospective longitudinal study investigated the association
      between baseline objectively measured sedentary time and 2-year onset of physical
      frailty. METHODS: We studied 1333 Osteoarthritis Initiative participants 55 to 83
      years of age who were at risk for physical frailty, as assessed via low gait
      speed (< 0.6 m per second) or inability to perform a single chair stand. Baseline
      sedentary time was assessed through accelerometer monitoring. Hazard ratios (HRs)
      for physical frailty onset were estimated with discrete survival methods that
      controlled for moderate physical activity, sociodemographic characteristics,
      baseline gait and chair stand functioning, and health factors. RESULTS: The
      incidence of physical frailty in this high-risk group was 20.7 per 1000 person
      years. Greater baseline sedentary time (adjusted HR = 1.36 per sedentary hour;
      95% confidence interval [CI] = 1.02, 1.79) was significantly related to incident
      physical frailty after control for time spent in moderate-intensity activities
      and other covariates. CONCLUSIONS: Our prospective data demonstrated a strong
      relationship between daily sedentary time and development of physical frailty
      distinct from insufficient moderate activity. Interventions that promote
      reductions in sedentary behaviors in addition to increases in physical activity
      may help decrease physical frailty onset.

PMID- 25973827
TI  - The Interaction Between an Individual's Acculturation and Community Factors on
      Physical Inactivity and Obesity: A Multilevel Analysis.
AB  - OBJECTIVES: We examined whether the interactions between primarily speaking
      English at home and community-level measures (median household income and
      immigrant composition) are associated with physical inactivity and obesity.
      METHODS: We pooled the 2005 and 2007 Los Angeles County Health Survey data to
      construct a multilevel data set, with community-level median household income and
      immigrant density as predictors at the community level. After controlling for
      individual-level demographic variables, we included the respondent's perceived
      community safety as a covariate to test the hypothesis that perceived public
      safety mediates the association between acculturation and health outcomes.
      RESULTS: The interaction between community median household income and primarily
      speaking English at home was associated with lower likelihoods of physical
      inactivity (odds ratio [OR] = 0.644; 95% confidence interval [CI] = 0.502, 0.825)
      and obesity (OR = 0.674; 95% CI = 0.514, 0.882). These odds remained significant
      after we controlled for perceived community safety. CONCLUSIONS: Resources in
      higher-income areas may be beneficial only to residents fully integrated into the
      community. Future research could focus on understanding how linguistic isolation
      affects community-level social learning and access to resources and whether this
      differs by family-level acculturation.

PMID- 25973828
TI  - Initiation of Human Papillomavirus Vaccination Among Predominantly Minority
      Female and Male Adolescents at Inner-City Community Health Centers.
AB  - OBJECTIVES: We examined the prevalence and correlates of human papillomavirus
      (HPV) vaccine initiation among adolescents in low-income, urban areas. METHODS:
      The study consisted of electronic health record data on HPV vaccination for 3180
      adolescents (aged 10-20 years) at a multisite community health center in 2011.
      RESULTS: Only 27% initiated the HPV vaccine. The adjusted odds ratio (AOR) of HPV
      vaccination was lower among older adolescents (AOR = 0.552; 95% confidence
      interval [CI] = 0.424, 0.718) and those seen by nonpediatric health care
      providers (HCPs; AOR = 0.311; 95% CI = 0.222, 0.435), and higher among non
      English speakers (AOR = 1.409; 95% CI = 1.134, 1.751) and those seen at 2 site
      locations (AOR = 1.890; 95% CI = 1.547, 2.311). Insurance status was significant
      only among female and Hispanic adolescents. Language was not a predictor among
      Hispanic adolescents. Across all analyses, the interaction of age and HCP
      specialty was associated with HPV vaccination. Dramatically lower HPV vaccination
      rates were found among older adolescents seen by nonpediatric HCPs (3%-5%) than
      among other adolescents (23%-45%). CONCLUSIONS: Improving HPV vaccination
      initiation in low-income urban areas is critical to reducing disparities in
      cervical and other HPV-related cancer, especially among Black, Hispanic, and low
      income populations.

PMID- 25973829
TI  - Transit Use, Physical Activity, and Body Mass Index Changes: Objective Measures
      Associated With Complete Street Light-Rail Construction.
AB  - OBJECTIVES: We assessed effects on physical activity (PA) and weight among
      participants in a complete street intervention that extended a light-rail line in
      Salt Lake City, Utah. METHODS: Participants in the Moving Across Places Study
      resided within 2 kilometers of the new line. They wore accelerometers and global
      positioning system (GPS) loggers for 1 week before and after rail construction.
      Regression analyses compared change scores of participants who never rode transit
      with continuing, former, and new riders, after adjustment for control variables
      (total n = 537). RESULTS: New riders had significantly more accelerometer
      measured counts per minute than never-riders (P < .01), and former riders had
      significantly fewer (P < .01). New riders lost (P < .05) and former riders gained
      (P < .01) weight. Former riders lost 6.4 minutes of moderate-to-vigorous PA
      (MVPA) per 10 hours of accelerometer wear (P < .01) and gained 16.4 minutes of
      sedentary time (P < .01). New riders gained 4.2 MVPA minutes (P < .05) and lost
      12.8 (P < .05) sedentary minutes per 10 hours accelerometer wear. CONCLUSIONS: In
      light of the health benefits of transit ridership in the complete street area,
      research should address how to encourage more sustained ridership.

PMID- 25973831
TI  - Comfortably, Safely, and Without Shame: Defining Menstrual Hygiene Management as
      a Public Health Issue.
AB  - In recent years, the menstrual hygiene management challenges facing schoolgirls
      in low-income-country contexts have gained global attention. We applied
      Gusfield's sociological analysis of the culture of public problems to better
      understand how this relatively newly recognized public health challenge rose to
      the level of global public health awareness and action. We similarly applied the
      conceptualization by Dorfman et al. of the role of public health messaging in
      changing corporate practice to explore the conceptual frames and the news frames
      that are being used to shape the perceptions of menstrual hygiene management as
      an issue of social justice within the context of public health. Important lessons
      were revealed for getting other public health problems onto the global-, national
      , and local-level agendas. 

PMID- 25973830
TI  - The Supplemental Nutrition Assistance Program, Food Insecurity, Dietary Quality,
      and Obesity Among U.S. Adults.
AB  - OBJECTIVES: We examined whether Supplemental Nutrition Assistance Program (SNAP)
      participation changes associations between food insecurity, dietary quality, and
      weight among US adults. METHODS: We analyzed adult dietary intake data (n = 8333)
      from the 2003 to 2010 National Health and Nutrition Examination Survey. Bivariate
      and multivariable methods assessed associations of SNAP participation and 4
      levels of food security with diet and weight. Measures of dietary quality were
      the Healthy Eating Index 2010, total caloric intake, empty calories, and solid
      fat; weight measures were body mass index (BMI), overweight, and obesity.
      RESULTS: SNAP participants with marginal food security had lower BMI (1.83 kg/m2;
      P < .01) and lower probability of obesity (9 percentage points; P < .05). SNAP
      participants with marginal (3.46 points; P < .01), low (1.98 points; P < .05),
      and very low (3.84 points; P < .01) food security had better diets, as
      illustrated by the Healthy Eating Index. Associations between SNAP participation
      and improved diet and weight were stronger among Whites than Blacks and
      Hispanics. CONCLUSIONS: Our research highlights the role of SNAP in helping
      individuals who are at risk for food insecurity to obtain a healthier diet and
      better weight status.

PMID- 25973832
TI  - The Role of Young Adults' Pleasure Attitudes in Shaping Condom Use.
AB  - Condoms can help young adults protect themselves from sexually transmitted
      infections and unintended pregnancy. We examined young people's attitudes about
      whether condoms reduced pleasure and how these attitudes shape condom practices.
      We used a nationally representative sample of 2328 heterosexually active,
      unmarried 15- to 24-year-old young adults to document multivariate associations
      with condom nonuse at the last sexual episode. For both young men and women,
      pleasure-related attitudes were more strongly associated with lack of condom use
      than all sociodemographic or sexual history factors. Research and interventions
      should consistently assess and address young people's attitudes about how condoms
      affect pleasure. 

PMID- 25973833
TI  - HIV and Sexually Transmitted Infection Testing Among High-Risk Youths: Supporting
      Positive Opportunities With Teens (SPOT) Youth Center.
AB  - OBJECTIVES: We investigated the development of and service utilization at
      Supporting Positive Opportunities with Teens (SPOT)-a community-based health and
      social service facility in St. Louis, Missouri, for youths that focuses on
      increasing HIV and sexually transmitted infection (STI) testing. METHODS: We
      identified the US-based, co-located youth health and social service models that
      guided the establishment of the SPOT. We analyzed the first 5 years (2008-2013)
      of service delivery and utilization data. RESULTS: During the study period, the
      SPOT provided services for 8233 youths in 37,480 visits. The 5 most utilized
      services included HIV and STI screening, food, transportation, contraception, and
      case management. A total of 9812 gonorrhea and chlamydia screenings revealed 1379
      (14.1%) cases of chlamydia and 437 (4.5%) cases of gonorrhea, and 5703 HIV tests
      revealed 59 HIV infections (1.0%); 93.0% of patients found to have an STI were
      treated within a 5-day window. CONCLUSIONS: Co-locating health and social
      services in informal community settings attracts high-risk youths to utilize
      services and can prove instrumental in reducing STI burden in this population.

PMID- 25973834
TI  - Community-Based Review of Research Across Diverse Community Contexts: Key
      Characteristics, Critical Issues, and Future Directions.
AB  - A growing number of community-based organizations and community-academic
      partnerships are implementing processes to determine whether and how health
      research is conducted in their communities. These community-based research review
      processes (CRPs) can provide individual and community-level ethics protections,
      enhance the cultural relevance of study designs and competence of researchers,
      build community and academic research capacity, and shape research agendas that
      benefit diverse communities. To better understand how they are organized and
      function, representatives of 9 CRPs from across the United States convened in
      2012 for a working meeting. In this article, we articulated and analyzed the
      models presented, offered guidance to communities that seek to establish a CRP,
      and made recommendations for future research, practice, and policy. 

PMID- 25973835
TI  - Novel organic dyes for multicolor localization-based super-resolution microscopy.
AB  - Precise multicolor single molecule localization-based microscopy (SMLM) requires
      bright probes with compatible photo-chemical and spectral properties to resolve
      distinct molecular species at the nanoscale. The accuracy of multicolor SMLM is
      further challenged by color channel crosstalk and chromatic alignment errors.
      These constrains limit the applicability of known reversibly switchable organic
      dyes for optimized multicolor SMLM. Here, we tested 28 commercially available
      dyes for their suitability to super-resolve a known cellular nanostructure. We
      identified eight novel dyes in different spectral regimes that enable high
      quality dSTORM imaging. Among those, the spectrally close dyes CF647 and CF680
      comprise an optimal dye pair for spectral demixing-based, registration free
      multicolor dSTORM with low crosstalk. Combining this dye pair with the separately
      excited CF568 we performed 3-color dSTORM to image the relative nanoscale
      distribution of components of the endocytic machinery and the cytoskeleton.

PMID- 25973836
TI  - Correction: Symmorphosis through Dietary Regulation: A Combinatorial Role for
      Proteolysis, Autophagy and Protein Synthesis in Normalising Muscle Metabolism and
      Function of Hypertrophic Mice after Acute Starvation.

PMID- 25973837
TI  - Response.

PMID- 25973838
TI  - Comparison of clipping with and without epinephrine injection for the prevention
      of post-polypectomy bleeding in pedunculated colon polyps.
AB  - BACKGROUND AND AIM: Post-polypectomy bleeding (PPB) is the most common adverse
      event of colonoscopic polypectomy, especially in cases with large pedunculated
      polyps. To minimize the risk of PPB, several endoscopic preventive methods have
      been performed. The aim of this prospective, randomized study was to compare the
      rates of PPB following single (clipping alone) and combined (clipping plus
      epinephrine-saline injection) methods in prevention of PPB in large pedunculated
      polyps. METHODS: Adult patients with pedunculated colorectal polyps with heads >=
      10 mm were prospectively enrolled from March 2011 to January 2013. Patients were
      randomized to receive treatment of either clips alone (group A) or clips plus
      injection of epinephrine-saline (group B) prior to a conventional polypectomy.
      PPB rate in both groups were compared. RESULTS: A total of 148 patients with 173
      pedunculated colorectal polyps were enrolled. Groups A and B each had 74
      patients, with 83 and 90 polyps, respectively. The mean head diameters were 17.2
      +/- 6.6 and 17.5 +/- 6.7 mm in groups A and B, respectively (P = 0.748).
      Immediate PPB (IPPB) occurred in 10 cases (12.0%) from group A and 13 cases
      (14.4%) from group B (P = 0.64). There were no cases of delayed PPB or
      perforation. Multivariate analysis showed that inadequate bowel preparation and
      large head diameter of polyp were independent risk factors for IPPB. CONCLUSIONS:
      The rate of IPPB is relatively high in cases with large pedunculated polyps, but
      these polyps can be successfully resected by snare polypectomy following use of
      the single prophylactic clipping method.

PMID- 25973839
TI  - Influence of Monomer Mixing Ratio on Membrane Nanostructure in Interfacial
      Polycondensation: Application of Hybrid MC/MD Reaction Method with Minimum Bond
      Convention.
AB  - FT-30, a typical aromatic polyamide membrane, is formed by interfacial
      polycondensation (IP) reaction between m-phenylenediamine (MPD) and benzene 1,3,5
      tricarboxylic acid chloride (TMC) monomers. To investigate its microscopic
      characteristics, we performed an atomistic molecular simulation using the hybrid
      MC/MD reaction method modified to allow intercellular chemical bonds stretching
      over the periodic boundaries. Starting with appropriate monomer model systems, we
      succeeded in making membrane models by simulating a succession of condensation
      reactions. Through an analysis comparing our calculation results for the degrees
      of polymer cross-linking (DPC) and the composition ratios to the experimental
      results, we clarified the MPD/TMC mixing ratios in the near-surface active (NSA)
      and interior active (IA) regions associated with the reaction mechanism of IP.
      Further, we executed water diffusion simulations using the membrane model of the
      IA region and showed the calculated values of the total mass density of the
      hydrated membrane and the partition coefficient K to be in good agreement with
      the experimental ones. In conclusion, the present computationally modeled
      polyamide membrane has sufficient fidelity to the actual membrane and should be
      considered a stable spatial structure in the local equilibrium state under a
      nonequilibrium stationary state of permeation. 

PMID- 25973840
TI  - Temperament and the mother-infant dyad: associations with breastfeeding and
      formula feeding with a bottle.
AB  - Breastfeeding supports the formation of an emotional bond between mothers and
      their children. The feeding method is associated with both the child's
      temperament and the mother's perception of herself and the child. Therefore, the
      present study focuses on the feeding method, mothers' reaction during feeding,
      and infants' temperament traits. Ninety-eight mothers with children aged 3 to 5
      months participated in the study. Children were assessed with the Children
      Development Scale (A. Matczak et al., 2007) to measure their temperament. Mothers
      completed the Mother and Baby Scale (D. Wolke & I. St James-Roberts, 1987, as
      cited in T.B. Brazelton & K. Nugent, 1995), which measures mothers' evaluation of
      their children's behaviors during feeding and their overall experiences with
      their children's care. The results show that breastfed newborns, as compared to
      bottle-fed newborns, demonstrate higher vigor, which includes activity and the
      intensity of reaction. Bottle-fed children demonstrate higher regularity than do
      breastfed children. Mothers who bottle-feed their children perceive themselves to
      be less confident in the feeding domain than do mothers who breastfeed. Our
      results indicate that children's temperament might be an important factor in the
      decision regarding the feeding method. The study supports the idea of promoting
      knowledge of children's behaviors during feeding among mothers even before their
      children are born, such as during antenatal classes. 

PMID- 25973841
TI  - Lateral Semicircular Canal-enlarged Vestibular Aqueduct Fistula Associated With
      Paroxysmal Positional Nystagmus.

PMID- 25973842
TI  - Autophony in a Patient With Giant Cell Tumor of the Temporal Bone.

PMID- 25973843
TI  - Accuracy issues involved in modeling in vivo protein structures using PM7.
AB  - Using the semiempirical method PM7, an attempt has been made to quantify the
      error in prediction of the in vivo structure of proteins relative to X-ray
      structures. Three important contributory factors are the experimental limitations
      of X-ray structures, the difference between the crystal and solution
      environments, and the errors due to PM7. The geometries of 19 proteins from the
      Protein Data Bank that had small R values, that is, high accuracy structures,
      were optimized and the resulting drop in heat of formation was calculated.
      Analysis of the changes showed that about 10% of this decrease in heat of
      formation was caused by faults in PM7, the balance being attributable to the X
      ray structure and the difference between the crystal and solution environments. A
      previously unknown fault in PM7 was revealed during tests to validate the
      geometries generated using PM7. Clashscores generated by the Molprobity molecular
      mechanics structure validation program showed that PM7 was predicting
      unrealistically close contacts between nonbonding atoms in regions where the
      local geometry is dominated by very weak noncovalent interactions. The origin of
      this fault was traced to an underestimation of the core-core repulsion between
      atoms at distances smaller than the equilibrium distance.

PMID- 25973844
TI  - Antibody recognition in multiple sclerosis and Rett syndrome using a collection
      of linear and cyclic N-glucosylated antigenic probes.
AB  - Antibody detection in autoimmune disorders, such as multiple sclerosis (MS) and
      Rett syndrome (RTT) can be achieved more efficiently using synthetic peptides.
      The previously developed synthetic antigenic probe CSF114(Glc), a type I' beta
      turn N-glucosylated peptide structure, is able to recognize antibodies in MS and
      RTT patients' sera as a sign of immune system derangement. We report herein the
      design, synthesis, conformational analysis, and immunological evaluation of a
      collection of glycopeptide analogs of CSF114(Glc) to characterize the specific
      role of secondary structures in MS and RTT antibody recognition. Therefore, we
      synthesized a series of linear and cyclic short glucosylated sequences, mimicking
      different beta-turn conformations, which were evaluated in inhibition enzyme
      linked immunosorbent assays (ELISA). Calculated IC50 ranking analysis allowed the
      selection of the candidate octapeptide containing two (S)-2-amino-4-pentynoic
      acid (L-Pra) residues Ac-Pra-RRN(Glc)GHT-Pra-NH2 , with an IC50 in the nanomolar
      range. This peptide was adequately modified for solid-phase ELISA (SP-ELISA) and
      surface plasmon resonance (SPR) experiments. Pra-RRN(Glc)GHT-Pra-NH2 peptide was
      modified with an alkyl chain linked to the N-terminus, favoring immobilization on
      solid phase in SP-ELISA and differentiating IgG antibody recognition between
      patients and healthy blood donors with a high specificity. However, this peptide
      displayed a loss in IgM specificity and sensitivity. Moreover, an analog was
      obtained after modification of the octapeptide candidate Ac-Pra-RRN(Glc)GHT-Pra
      NH2 to favor immobilization on SPR sensor chips. SPR technology allowed us to
      determine its affinity (KD  = 16.4 nM), 2.3 times lower than the affinity of the
      original glucopeptide CSF114(Glc) (KD  = 7.1 nM).

PMID- 25973845
TI  - Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the
      Diagnosis of Schistosoma haematobium in Low Endemic Settings.
AB  - BACKGROUND: Elimination of schistosomiasis as a public health problem and
      interruption of transmission in selected areas are key goals of the World Health
      Organization for 2025. Conventional parasitological methods are insensitive for
      the detection of light-intensity infections. Techniques with high sensitivity and
      specificity are required for an accurate diagnosis in low-transmission settings
      and verification of elimination. We determined the accuracy of a urine-based up
      converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay
      for Schistosoma haematobium diagnosis in low-prevalence settings in Zanzibar,
      Tanzania. METHODOLOGY: A total of 1,740 urine samples were collected in 2013 from
      children on Pemba Island, from schools where the S. haematobium prevalence was
      <2%, 2-5%, and 5-10%, based on a single urine filtration. On the day of
      collection, all samples were tested for microhematuria with reagent strips and
      for the presence of S. haematobium eggs with microscopy. Eight months later, 1.5
      ml of urine from each of 1,200 samples stored at -20 degrees C were analyzed by
      UCP-LF CAA assay, while urine filtration slides were subjected to quality control
      (QCUF). In the absence of a true 'gold' standard, the diagnostic performance was
      calculated using latent class analyses (LCA). PRINCIPAL FINDINGS: The 'empirical'
      S. haematobium prevalence revealed by UCP-LF CAA, QCUF, and reagent strips was
      14%, 5%, and 4%, respectively. LCA revealed a sensitivity of the UCP-LF CAA,
      QCUF, and reagent strips of 97% (95% confidence interval (CI): 91-100%), 86% (95%
      CI: 72-99%), and 67% (95% CI: 52-81%), respectively. Test specificities were
      consistently above 90%. CONCLUSIONS/SIGNIFICANCE: The UCP-LF CAA assay shows high
      sensitivity for the diagnosis of S. haematobium in low-endemicity settings.
      Empirically, it detects a considerably higher number of infections than
      microscopy. Hence, the UCP-LF CAA employed in combination with QCUF, is a
      promising tool for monitoring and surveillance of urogenital schistosomiasis in
      low-transmission settings targeted for elimination.

PMID- 25973847
TI  - Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory
      Responses in the Liver and White Adipose Tissue.
AB  - BACKGROUND/HYPOTHESIS: Beside its beneficial effects on weight loss, ketogenic
      diet (KD) causes dyslipidemia, a pro-inflammatory state involved in the
      development of hepatic steatosis, glucose intolerance and insulin resistance,
      although the latter is still being debated. Additionally, KD is known to increase
      fibroblast growth factor 21 (FGF21) plasma levels. However, FGF21 cannot initiate
      its beneficial actions on metabolism in these conditions. We therefore
      hypothesized and tested in the present study that KD may impair FGF21 signaling.
      METHODS/RESULTS: Using indirect calorimetry, we found that KD-fed mice exhibited
      higher energy expenditure than regular chow (RC)-fed mice associated with
      increased Ucp1 levels in white adipose tissue (WAT), along with increased plasma
      FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the
      liver and WAT. We found that Fgfr4 and Klb (beta-klotho) were downregulated in
      the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because
      inflammation could be one of the mechanisms linking KD to impaired FGF21
      signaling, we measured the expression levels of inflammatory markers and
      macrophage accumulation in WAT and liver and found an increased inflammation and
      macrophage accumulation in the liver, but surprisingly, a reduction of
      inflammation in WAT.We also showed that KD enhances lipid accumulation in the
      liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb
      expression. In contrast, import of lipids from the circulation was significantly
      reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36.
      This was further associated with reduced inflammation in WAT. CONCLUSION:
      Altogether, these results indicate that KD could be beneficial for a given tissue
      but deleterious for another.

PMID- 25973846
TI  - Expression of GITR Enhances Multiple Myeloma Cell Sensitivity to Bortezomib.
AB  - Recently tumor necrosis factor receptor super family member 18 (TNFRSF18, also
      called GITR) has been identified as a novel tumor suppressor gene in Multiple
      Myeloma (MM), undergoing aberrant DNA methylation-mediated gene expression
      silencing. Furthermore, the expression of GITR blocks canonical NF-kappaB
      activation in MM cells in response to TNFalpha. Bortezomib, a proteasome
      inhibitor, can induce NF-kappaB activation, which may significantly influence the
      drug response in MM patients. In this study, we aim to elucidate if GITR status
      is associated with response to Bortezomib in MM cells through regulating GITR
      mediated NF-kappaB blockade. We found that GITR was significantly downregulated
      in MM patients and cell lines. Overexpression of GITR inhibited non-canonical NF
      kappaB activation induced by TNFalpha. Moreover, NF-kappaB inhibitor induced
      apoptosis in GITR-deficient MM cells in response to TNFalpha. In addition,
      overexpression of GITR could inhibit Bortezomib-induced NF-kappaB activation and
      enhance the cytotoxicity of Bortezomib in GITR-deficient MM cell line (MM1.S). In
      contrast, knockdown of GITR attenuated the cytotoxic effect of Bortezomib on GITR
      proficient MM (RPMI) cell line and increased NF-kappaB activation. Finally,
      overexpression of GITR enhanced the sensitivity to Bortezomib in co-culture with
      bone marrow stromal cells and significantly reduced the tumor growth in MM1.S
      xenograft mice. In conclusion, we demonstrated that GITR expression can enhance
      the sensitivity to Bortezomib by inhibiting Bortezomib-induced NF-kappaB
      activation. 

PMID- 25973848
TI  - Differential Genes Expression between Fertile and Infertile Spermatozoa Revealed
      by Transcriptome Analysis.
AB  - BACKGROUND: It was believed earlier that spermatozoa have no traces of RNA
      because of loss of most of the cytoplasm. Recent studies have revealed the
      presence of about 3000 different kinds of mRNAs in ejaculated spermatozoa.
      However, the correlation of transcriptome profile with infertility remains
      obscure. METHODS: Total RNA from sperm (after exclusion of somatic cells) of 60
      men consisting of individuals with known fertility (n=20), idiopathic infertility
      (normozoospermic patients, n=20), and asthenozoospermia (n=20) was isolated.
      After RNA quality check on Bioanalyzer, AffymetrixGeneChip Human Gene 1.0 ST
      Array was used for expression profiling, which consisted of >30,000 coding
      transcripts and >11,000 long intergenic non-coding transcripts. RESULTS:
      Comparison between all three groups revealed that two thousand and eighty one
      transcripts were differentially expressed. Analysis of these transcripts showed
      that some transcripts [ribosomal proteins (RPS25, RPS11, RPS13, RPL30, RPL34,
      RPL27, RPS5), HINT1, HSP90AB1, SRSF9, EIF4G2, ILF2] were up-regulated in the
      normozoospermic group, but down-regulated in the asthenozoospermic group in
      comparison to the control group. Some transcripts were specific to the
      normozoospermic group (up-regulated: CAPNS1, FAM153C, ARF1, CFL1, RPL19, USP22;
      down-regulated: ZNF90, SMNDC1, c14orf126, HNRNPK), while some were specific to
      the asthenozoospermic group (up-regulated: RPL24, HNRNPM, RPL4, PRPF8, HTN3,
      RPL11, RPL28, RPS16, SLC25A3, C2orf24, RHOA, GDI2, NONO, PARK7; down-regulated:
      HNRNPC, SMARCAD1, RPS24, RPS24, RPS27A, KIFAP3). A number of differentially
      expressed transcripts in spermatozoa were related to reproduction (n = 58) and
      development (n= 210). Some of these transcripts were related to heat shock
      proteins (DNAJB4, DNAJB14), testis specific genes (TCP11, TESK1, TSPYL1, ADAD1),
      and Y-chromosome genes (DAZ1, TSPYL1). CONCLUSION: A complex RNA population in
      spermatozoa consisted of coding and non-coding RNAs. A number of transcripts that
      participate in a host of cellular processes, including reproduction and
      development were differentially expressed between fertile and infertile
      individuals. Differences between comparison groups suggest that sperm RNA has
      strong potential of acting as markers for fertility evaluation.

PMID- 25973849
TI  - A new anatomical approach to laparoscopic hernia repair: Triangle of dissection.

PMID- 25973850
TI  - Metabolic Disposition and Elimination of Cyadox in Pigs, Chickens, Carp, and
      Rats.
AB  - The metabolism, distribution, and elimination of cyadox (CYA) is investigated in
      pigs, chickens, carp, and rats to identify the marker residue and target tissue
      of CYA in food animals for food safety concerns. Following a single oral gavage
      of [(3)H]-CYA, the total radioactivity was rapidly excreted, with more than 95%
      of the dose excreted within 14 days in the four species. Fecal excretion of the
      total radioactivity was 66.2% and 51.6%, and urinary excretion of the total
      radioactivity was 28.35% and 44.3% in rats and pigs, respectively. Radioactivity
      was observed in nearly all of the tissues in the first 6 h after 7 days of
      consecutive oral dosing. The highest radioactivity and longest persistence were
      in the livers and kidneys, where the majority of the radioactivity was cleared
      within 7 days. A total of 15 metabolites were identified in rats, pigs, chickens,
      and carp, and eight new metabolites were identified for the first time in vivo.
      No parent drug could be detected in the tissues of rats and pigs. The major
      metabolites of CYA were Cy1, Cy3, and Cy6 in pigs, Cy1, Cy5, and Cy6 in chickens,
      Cy1, Cy2, and Cy4 in carp, and Cy1, Cy2, Cy4, and Cy5 in rats. Cy1 was suggested
      to be the marker residue, and the kidneys were identified as the target tissue of
      CYA in pigs and chickens. These results provide comprehensive information for the
      food safety evaluation of CYA in food animals and will improve the understanding
      of the pharmacology and toxicology of CYA in animals. 

PMID- 25973852
TI  - High activity of an indium alkoxide complex toward ring opening polymerization of
      cyclic esters.
AB  - An indium complex supported by a ferrocene-derived Schiff base ligand has an
      unprecedented high activity toward epsilon-caprolactone, delta-valerolactone, and
      beta-butyrolactone. l-Lactide, d,l-lactide, and trimethylene carbonate
      polymerizations also showed moderate to high activity. 

PMID- 25973851
TI  - Est10: A Novel Alkaline Esterase Isolated from Bovine Rumen Belonging to the New
      Family XV of Lipolytic Enzymes.
AB  - A metagenomic fosmid library from bovine rumen was used to identify clones with
      lipolytic activity. One positive clone was isolated. The gene responsible for the
      observed phenotype was identified by in vitro transposon mutagenesis and
      sequencing and was named est10. The 367 amino acids sequence harbors a signal
      peptide, the conserved secondary structure arrangement of alpha/beta hydrolases,
      and a GHSQG pentapeptide which is characteristic of esterases and lipases.
      Homology based 3D-modelling confirmed the conserved spatial orientation of the
      serine in a nucleophilic elbow. By sequence comparison, Est10 is related to
      hydrolases that are grouped into the non-specific Pfam family DUF3089 and to
      other characterized esterases that were recently classified into the new family
      XV of lipolytic enzymes. Est10 was heterologously expressed in Escherichia coli
      as a His-tagged fusion protein, purified and biochemically characterized. Est10
      showed maximum activity towards C4 aliphatic chains and undetectable activity
      towards C10 and longer chains which prompted its classification as an esterase.
      However, it was able to efficiently catalyze the hydrolysis of aryl esters such
      as methyl phenylacetate and phenyl acetate. The optimum pH of this enzyme is 9.0,
      which is uncommon for esterases, and it exhibits an optimal temperature at 40 
      degrees C. The activity of Est10 was inhibited by metal ions, detergents,
      chelating agents and additives. We have characterized an alkaline esterase
      produced by a still unidentified bacterium belonging to a recently proposed new
      family of esterases.

PMID- 25973853
TI  - Resting State-fMRI with ReHo Analysis as a Non-Invasive Modality for the
      Prognosis of Cirrhotic Patients with Overt Hepatic Encephalopathy.
AB  - BACKGROUND: To investigate the relationships among regional activity
      abnormalities, clinical disease severity, and prognosis in cirrhotic patients
      with overt hepatic encephalopathy (OHE) using resting-state functional magnetic
      resonance imaging (rs-fMRI). METHODS: Regional homogeneity (ReHo) values of 12
      cirrhotic patients with OHE and 12 age- and sex-matched healthy volunteers were
      calculated from rs-fMRI. Two-sample t-test was performed on individual ReHo maps
      between the two groups. The relationships between ReHo variation, disease
      severity, and prognosis were analyzed. RESULTS: Cirrhotic patients with OHE had
      significantly low ReHo values in the left middle cingulum, bilateral superior
      temporal, left inferior orbito-frontal, right calcarine, left inferior frontal
      gyrus, left post-central, left inferior temporal, and left lingual areas, and
      high ReHo in the right superior frontal, right inferior temporal, right caudate,
      and cerebellum. There was significant group difference in the right superior
      temporal lobe (p=0.016) and crus1 of the left cerebellum (p=0.015) between
      survivors and non-survivors in the OHE group. Worse Glasgow Coma Scale was
      associated with increased local connectivity in the left cerebellar crus I (r=
      0.868, p=0.001). CONCLUSIONS: Information on the functional activity of cirrhotic
      patients with OHE suggests the use of rs-fMRI with ReHo analysis as a non
      invasive prognosticating modality.

PMID- 25973854
TI  - Climatic Stress during Stand Development Alters the Sign and Magnitude of Age
      Related Growth Responses in a Subtropical Mountain Pine.
AB  - The modification of typical age-related growth by environmental changes is poorly
      understood, In part because there is a lack of consensus at individual tree level
      regarding age-dependent growth responses to climate warming as stands develop. To
      increase our current understanding about how multiple drivers of environmental
      change can modify growth responses as trees age we used tree ring data of a
      mountain subtropical pine species along an altitudinal gradient covering more
      than 2,200 m of altitude. We applied mixed-linear models to determine how
      absolute and relative age-dependent growth varies depending on stand development;
      and to quantify the relative importance of tree age and climate on individual
      tree growth responses. Tree age was the most important factor for tree growth in
      models parameterised using data from all forest developmental stages.
      Contrastingly, the relationship found between tree age and growth became non
      significant in models parameterised using data corresponding to mature stages.
      These results suggest that although absolute tree growth can continuously
      increase along tree size when trees reach maturity age had no effect on growth.
      Tree growth was strongly reduced under increased annual temperature, leading to
      more constant age-related growth responses. Furthermore, young trees were the
      most sensitive to reductions in relative growth rates, but absolute growth was
      strongly reduced under increased temperature in old trees. Our results help to
      reconcile previous contrasting findings of age-related growth responses at the
      individual tree level, suggesting that the sign and magnitude of age-related
      growth responses vary with stand development. The different responses found to
      climate for absolute and relative growth rates suggest that young trees are
      particularly vulnerable under warming climate, but reduced absolute growth in old
      trees could alter the species' potential as a carbon sink in the future. 

PMID- 25973855
TI  - A single exposure of sediment sulphate-reducing bacteria to oxytetracycline
      concentrations relevant to aquaculture enduringly disturbed their activity,
      abundance and community structure.
AB  - AIM: Although feed medicated with antibiotics is widely used in animal production
      to prevent and treat bacterial infections, the effect of these drugs on nontarget
      anaerobic bacteria is unknown. We aimed to clarify whether a single exposure of
      sulphate-reducing bacteria (SRB) from a tilapia pond to oxytetracycline (OTC)
      concentrations relevant to aquaculture impacts their function, abundance and
      community structure. METHODS AND RESULTS: To demonstrate changes in SO4(2-)
      content, SRB abundance, dsrB copy number and SRB diversity, sediment mesocosms
      were spiked with 5, 25, 50 and 75 mg OTC kg(-1) and examined for 30 days by means
      of ion chromatography, qPCR, cultivation and fluorescent in situ hybridization
      (FISH). On day 3, we measured higher SO4(2-) concentrations (ca. two-fold) and a
      reduction in dsrB copy numbers of approximately 50% in the treatments compared to
      the controls. After 30 days, a subtle yet measurable enrichment of bacteria from
      the order Desulfovibrionales occurred in mesocosms receiving >= 50 mg OTC kg(-1),
      notwithstanding that SRB counts decreased two orders of magnitude. OTC was
      dynamically and reversibly converted into 4-epioxytetracycline and other related
      compounds in a dose-dependent manner during the experiment. CONCLUSIONS: A single
      exposure to rather high OTC concentrations triggered functional and structural
      changes in a SRB community that manifested quickly and persisted for a month.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study improves our limited knowledge
      on the ecotoxicology of antibiotics in anaerobic environments.

PMID- 25973857
TI  - Exploiting the richest patch has a fitness pay-off for the migratory swift
      parrot.
AB  - 1. Unlike philopatric migrants, the ecology of nomadic migrants is less well
      understood. This life-history strategy reflects responses to spatiotemporal
      variation in resource availability and the need to find resource rich patches to
      initiate breeding. The fitness consequences of movements between regions of
      patchily distributed resources can provide insight into ecology of all migrants
      and their responses to global change. 2. We link broad-scale data on
      spatiotemporal fluctuation in food availability to data on settlement patterns
      and fitness outcomes for a nomadic migrant, the endangered swift parrot Lathamus
      discolor. We test several predictions to determine whether facultative movements
      are adaptive for individual swift parrots in an environment where resources are
      patchily distributed over time and space. 3. Variation in the availability of
      swift parrot food resources across our study period was dramatic. As a
      consequence, swift parrots moved to breed wherever food was most abundant and did
      not resettle nesting regions in successive years when food availability declined.
      By moving, swift parrots exploited a variable food resource and reproduced
      successfully. 4. Exploiting the richest patches allowed swift parrots to maintain
      stable fitness outcomes between discrete breeding events at different locations.
      Unlike sedentary species that often produce few or lower quality offspring when
      food is scarce, nomadic migration buffered swift parrots against extreme
      environmental variation. 5. We provide the first detailed evidence that
      facultative movements and nomadic migration are adaptive for individuals in
      unpredictable environments. Our data support the widely held assumption that
      nomadic migration allows animals to escape resource limitation.

PMID- 25973856
TI  - Coupling of Cellular Processes and Their Coordinated Oscillations under
      Continuous Light in Cyanothece sp. ATCC 51142, a Diazotrophic Unicellular
      Cyanobacterium.
AB  - Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142
      (henceforth Cyanothece), temporally separate the oxygen sensitive nitrogen
      fixation from oxygen evolving photosynthesis not only under diurnal cycles (LD)
      but also in continuous light (LL). However, recent reports demonstrate that the
      oscillations in LL occur with a shorter cycle time of ~11 h. We find that indeed,
      majority of the genes oscillate in LL with this cycle time. Genes that are
      upregulated at a particular time of day under diurnal cycle also get upregulated
      at an equivalent metabolic phase under LL suggesting tight coupling of various
      cellular events with each other and with the cell's metabolic status. A number of
      metabolic processes get upregulated in a coordinated fashion during the
      respiratory phase under LL including glycogen degradation, glycolysis, oxidative
      pentose phosphate pathway, and tricarboxylic acid cycle. These precede nitrogen
      fixation apparently to ensure sufficient energy and anoxic environment needed for
      the nitrogenase enzyme. Photosynthetic phase sees upregulation of photosystem II,
      carbonate transport, carbon concentrating mechanism, RuBisCO, glycogen synthesis
      and light harvesting antenna pigment biosynthesis. In Synechococcus elongates PCC
      7942, a non-nitrogen fixing cyanobacteria, expression of a relatively smaller
      fraction of genes oscillates under LL condition with the major periodicity being
      24 h. In contrast, the entire cellular machinery of Cyanothece orchestrates
      coordinated oscillation in anticipation of the ensuing metabolic phase in both LD
      and LL. These results may have important implications in understanding the timing
      of various cellular events and in engineering cyanobacteria for biofuel
      production. 

PMID- 25973858
TI  - Use of CAH-degrading bacteria as test-organisms for evaluating the impact of fine
      zerovalent iron particles on the anaerobic subsurface environment.
AB  - The release of fine zerovalent iron (ZVI) particles in the environment after
      being introduced for in-situ treatment of compounds like chlorinated aliphatic
      hydrocarbons (CAHs) may raise questions toward environmental safety, especially
      for nanoscale materials. Classical single-species ecotoxicity tests do focus on
      aerobic conditions and are only relevant for the scenario when ZVI-particles
      reach surface water. Herein, we present an alternative approach where a CAH
      degrading mixed bacterial culture was used as test-organisms relevant for the
      anaerobic subsurface. The impact of different ZVI particles on the bacterial
      culture was evaluated mainly by quantifying ATP, a reporter molecule giving a
      general indication of the microbial activity. These lab-scale batch tests were
      performed in liquid medium, without protecting and buffering aquifer material, as
      such representing worst-case scenario. The activity of the bacterial culture was
      negatively influenced by nanoscale zerovalent iron at doses as low as 0.05 g L(
      1). On the other hand, concentrations up to 2 g L(-1) of several different types
      of microscale zerovalent iron (mZVI) particles stimulated the activity. However,
      very high doses of 15-30 g L(-1) of mZVI showed an inhibiting effect on the
      bacterial community. Negative effects of ZVIs were confirmed by H2 accumulation
      in the batch reactors and the absence of lactate consumption. Observed inhibition
      also corresponded to a pH increase above 7.5, explicable by ZVI corrosion that
      was found to be dose-dependent. The obtained results suggest that low doses of
      mZVIs will not show severe inhibition effects on the microbial community once
      used for in-situ treatment of CAHs.

PMID- 25973859
TI  - Detoxification of ashes from a fluidized bed waste incinerator.
AB  - This paper was to test and control the toxicity of bottom and fly ashes from a
      circulated fluidized bed (CFB) incinerator. Bottom and fly ashes were firstly
      subject to TCLP test. Even though leachates of most particle size of bottom ash
      were below regulatory limit, the leachates of finer bottom ash may exceed the
      regulatory limit. Therefore, finer bottom ash should be separated and treated
      before landfilled directly or used as cement replacement. Due to high amounts of
      leached heavy metals, thermal treatment of fly ash was carried out to remove
      heavy metals. The influence of temperature, residence time, metal chloride and
      gas velocity were studied. In all conditions, Cd can be well removed. Pb can be
      almost completely removed with MgCl2 addition at 1000 degrees C in 1h. The
      removal of Zn and Cu was accelerated significantly by MgCl2 and higher
      temperature separately. At optimum conditions, more than 90% of Cu and 95% of Zn
      could be removed, while a maximum 20% of Cr was removed due to the existence or
      formation of CaCr2O4, MgCr2O4 and K2Cr2O4 in raw or treated fly ashes. 

PMID- 25973860
TI  - NIR spectroscopy as a tool for discriminating between lichens exposed to air
      pollution.
AB  - Lichens are used as biomonitors of air pollution because they are extremely
      sensitive to the presence of substances that alter atmospheric composition. Fifty
      one thalli of two different varieties of Pseudevernia furfuracea (var. furfuracea
      and var. ceratea) were collected far from local sources of air pollution. Twenty
      six of these thalli were then exposed to the air for one month in the industrial
      port of Genoa, which has high levels of environmental pollution. The possibility
      of using Near-infrared spectroscopy (NIRS) for generating a 'fingerprint' of
      lichens was investigated. Chemometric methods were successfully applied to
      discriminate between samples from polluted and non-polluted areas. In particular,
      Principal Component Analysis (PCA) was applied as a multivariate display method
      on the NIR spectra to visualise the data structure. This showed that the
      difference between samples of different varieties was not significant in
      comparison to the difference between samples exposed to different levels of
      environmental pollution. Then Linear Discriminant Analysis (LDA) was carried out
      to discriminate between lichens based on their exposure to pollutants. The
      distinction between control samples (not exposed) and samples exposed to the air
      in the industrial port of Genoa was evaluated. On average, 95.2% of samples were
      correctly classified, 93.0% of total internal prediction (5 cross-validation
      groups) and 100.0% of external prediction (on the test set) was achieved. 

PMID- 25973861
TI  - Competitive adsorption/desorption of tetracycline, oxytetracycline and
      chlortetracycline on two acid soils: Stirred flow chamber experiments.
AB  - The objective of this work was to study the competitive adsorption/desorption of
      tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) on two acid
      soils. We used the stirred flow chamber technique to obtain experimental data on
      rapid kinetic processes affecting the retention/release of the antibiotics. Both
      adsorption and desorption were higher on soil 1 (which showed the highest carbon,
      clay and Al and Fe oxides content) than on soil 2. Moreover, hysteresis affected
      the adsorption/desorption processes. Experimental data were fitted to a pseudo
      first order equation, resulting qamax (adsorption maximum) values that were
      higher for soil 1 than for soil 2, and indicating that CTC competed with TC more
      intensely than OTC in soil 1. Regarding soil 2, the values corresponding to the
      adsorption kinetics constants (ka) and desorption kinetics constants for fast
      sites (kd1), followed a trend inverse to qamax and qdmax respectively. In
      conclusion, competition affected adsorption/desorption kinetics for the three
      antibiotics assayed, and thus retention/release and subsequent transport
      processes in soil and water environments. 

PMID- 25973862
TI  - Aromatic amine contents, component distributions and risk assessment in sludge
      from 10 textile-dyeing plants.
AB  - Aromatic amines (AAs), which are components of synthetic dyes, are recalcitrant
      to the wastewater treatment process and can accumulate in sludge produced by
      textile-dyeing, which may pose a threat to the environment. A comprehensive
      investigation of 10 textile-dyeing plants was undertaken in Guangdong Province in
      China. The contents and component distributions of AAs were evaluated in this
      study, and a risk assessment was performed. The total concentrations of 14 AAs
      (Sigma14 AAs) varied from 11 MUg g(-1)dw to 82.5 MUg g(-1)dw, with a mean value
      of 25 MUg g(-1)dw. The component distributions of AAs were characterized by
      monocyclic anilines, of which 2-methoxy-5-methylaniline and 5-nitro-o-toluidine
      were the most dominant components. The risk quotient (RQ) value was used to
      numerically evaluate the ecological risk of 14 AAs in the environment. The result
      showed that the 14 AAs contents in textile-dyeing sludge may pose a high risk to
      the soil ecosystem after being discarded on soil or in a landfill.

PMID- 25973865
TI  - A novel liquid/liquid extraction process composed of surfactant and acetonitrile
      for purification of polygalacturonase enzyme from Durio zibethinus.
AB  - Polygalacturonase is one of the important enzymes used in various industries such
      as food, detergent, pharmaceutical, textile, pulp and paper. A novel
      liquid/liquid extraction process composed of surfactant and acetonitrile was
      employed for the first time to purify polygalacturonase from Durio zibethinus.
      The influences of different parameters such as type and concentration of
      surfactants, concentrations of acetonitrile and composition of
      surfactant/acetonitrile on partitioning behavior and recovery of
      polygalacturonase was investigated. Moreover, the effect of pH of system and
      crude load on purification fold and yield of purified polygalacturonase were
      studied. The results of the experiment indicated the polygalacturonase was
      partitioned into surfactant top rich phase with impurities being partitioned into
      acetonitrile bottom rich phase in the novel method of liquid/liquid process
      composed of 23% (w/w) Triton X-100 and 19% (w/w) acetonitrile, at 55.6% of TLL
      (tie line length) crude load of 25% (w/w) at pH 6.0. Recovery and recycling of
      components also was measured in each successive step of liquid/liquid extraction
      process. The enzyme was successfully recovered by the method with a high
      purification factor of 14.3 and yield of 97.3% while phase components were also
      recovered and recycled above 95%. This study demonstrated that the novel method
      of liquid/liquid extraction process can be used as an efficient and economical
      extraction method rather than the traditional methods of extraction for the
      purification and recovery of the valuable enzyme. 

PMID- 25973864
TI  - Learning sequence determinants of protein:protein interaction specificity with
      sparse graphical models.
AB  - In studying the strength and specificity of interaction between members of two
      protein families, key questions center on which pairs of possible partners
      actually interact, how well they interact, and why they interact while others do
      not. The advent of large-scale experimental studies of interactions between
      members of a target family and a diverse set of possible interaction partners
      offers the opportunity to address these questions. We develop here a method,
      DgSpi (data-driven graphical models of specificity in protein:protein
      interactions), for learning and using graphical models that explicitly represent
      the amino acid basis for interaction specificity (why) and extend earlier
      classification-oriented approaches (which) to predict the DeltaG of binding (how
      well). We demonstrate the effectiveness of our approach in analyzing and
      predicting interactions between a set of 82 PDZ recognition modules against a
      panel of 217 possible peptide partners, based on data from MacBeath and
      colleagues. Our predicted DeltaG values are highly predictive of the
      experimentally measured ones, reaching correlation coefficients of 0.69 in 10
      fold cross-validation and 0.63 in leave-one-PDZ-out cross-validation.
      Furthermore, the model serves as a compact representation of amino acid
      constraints underlying the interactions, enabling protein-level DeltaG
      predictions to be naturally understood in terms of residue-level constraints.
      Finally, the model DgSpi readily enables the design of new interacting partners,
      and we demonstrate that designed ligands are novel and diverse. 

PMID- 25973866
TI  - Improved calibration of mass stopping power in low density tissue for a proton
      pencil beam algorithm.
AB  - Dose distributions for proton therapy treatments are almost exclusively
      calculated using pencil beam algorithms. An essential input to these algorithms
      is the patient model, derived from x-ray computed tomography (CT), which is used
      to estimate proton stopping power along the pencil beam paths. This study
      highlights a potential inaccuracy in the mapping between mass density and proton
      stopping power used by a clinical pencil beam algorithm in materials less dense
      than water. It proposes an alternative physically-motivated function (the mass
      average, or MA, formula) for use in this region. Comparisons are made between
      dose-depth curves calculated by the pencil beam method and those calculated by
      the Monte Carlo particle transport code MCNPX in a one-dimensional lung model.
      Proton range differences of up to 3% are observed between the methods, reduced to
      <1% when using the MA function. The impact of these range errors on clinical
      dose distributions is demonstrated using treatment plans for a non-small cell
      lung cancer patient. The change in stopping power calculation methodology results
      in relatively minor differences in dose when plans use three fields, but
      differences are observed at the 2%-2 mm level when a single field uniform dose
      technique is adopted. It is therefore suggested that the MA formula is adopted by
      users of the pencil beam algorithm for optimal dose calculation in lung, and that
      a similar approach is considered when beams traverse other low density regions
      such as the paranasal sinuses and mastoid process.

PMID- 25973863
TI  - Sudomotor innervation in transthyretin amyloid neuropathy: Pathology and
      functional correlates.
AB  - OBJECTIVE: Autonomic neuropathy is a major component of familial amyloid
      polyneuropathy (FAP) due to mutated transthyretin, with sudomotor failure as a
      common manifestation. This study aimed to investigate the pathology and clinical
      significance of sudomotor denervation. METHODS: Skin biopsies were performed on
      the distal leg of FAP patients with a follow-up duration of 3.8 +/- 1.6 years.
      Sudomotor innervation was stained with 2 markers: protein gene product 9.5 (PGP
      9.5), a general neuronal marker, and vasoactive intestinal peptide (VIP), a
      sudomotor nerve functional marker, followed by quantitation according to sweat
      gland innervation index (SGII) for PGP 9.5 (SGIIPGP 9.5) and VIP (SGIIVIP).
      RESULTS: There were 28 patients (25 men) with Ala97Ser transthyretin and late
      onset (59.9 +/- 6.0 years) disabling neuropathy. Autonomic symptoms were present
      in 22 patients (78.6%) at the time of skin biopsy. The SGIIPGP 9.5 and SGIIVIP of
      FAP patients were significantly lower than those of age- and gender-matched
      controls. The reduction of SGIIVIP was more severe than that of SGIIPGP 9.5 (p =
      0.002). Patients with orthostatic hypotension or absent sympathetic skin response
      at palms were associated with lower SGIIPGP 9.5 (p = 0.019 and 0.002,
      respectively). SGIIPGP 9.5 was negatively correlated with the disability grade at
      the time of skin biopsy (p = 0.004), and was positively correlated with the
      interval from the time of skin biopsy to the time of wheelchair usage (p =
      0.029). INTERPRETATION: This study documented the pathological evidence of
      sudomotor denervation in FAP. SGIIPGP 9.5 was functionally correlated with
      autonomic symptoms, autonomic tests, ambulation status, and progression of
      disability.

PMID- 25973867
TI  - Correction: Examining the Species-Specificity of Rhesus Macaque Cytomegalovirus
      (RhCMV) in Cynomolgus Macaques.

PMID- 25973868
TI  - Pericarditis as a window into the mind of the internist.

PMID- 25973869
TI  - To the Editor: Clinical utility of warfarin pharmacogenomics.

PMID- 25973870
TI  - A lump in the umbilicus.

PMID- 25973871
TI  - Annual mammography starting at age 40: More talk, less action?

PMID- 25973872
TI  - Screening mammography starting at age 40: Still relevant.

PMID- 25973873
TI  - Light-headedness and bradycardia in a 72-year-old woman.

PMID- 25973874
TI  - Morphea-like plaques, induration of the extremities, and eosinophilia.

PMID- 25973875
TI  - When does pericarditis merit a workup for autoimmune or inflammatory disease?

PMID- 25973876
TI  - A 79-year-old with acute portal vein thrombosis.

PMID- 25973877
TI  - Penicillin allergy: A practical guide for clinicians.
AB  - Penicillin allergy is the most commonly reported drug allergy in the United
      States. However, after undergoing a complete evaluation by a board-certified
      allergist, including skin testing, 90% of patients labeled as 'penicillin
      allergic' are able to tolerate penicillin. Clinical presentation is key in
      classifying reactions as either mediated by or not mediated by immunoglobulin E
      (IgE), and in determining which patients may benefit from penicillin skin
      testing, graded-dose challenge, or desensitization. Cross-reactivity between
      penicillin and other beta-lactams is less common than previously thought. 

PMID- 25973878
TI  - Stand by me! Reducing the risk of injurious falls in older adults.
AB  - About one-third of community-dwelling adults age 65 and older fall each year, and
      some suffer fractures, traumatic brain injury, and even death. Therefore, it is
      important to identify older adults at risk and recommend helpful interventions. 

PMID- 25973879
TI  - Dermatology update: The dawn of targeted treatment.
AB  - During the past several years, targeted therapies have significantly improved
      outcomes in advanced basal cell carcinoma, psoriasis, and metastatic melanoma.
      This article reviews how advances in our understanding of the molecular
      pathogenesis of these diseases led to the development of targeted therapies and
      how these therapies are improving outcomes. Research is ongoing to address
      continuing challenges of drug resistance, adverse effects, and how best to use
      the new medications. 

PMID- 25973880
TI  - Diarrheal Disease in Rural Mozambique: Burden, Risk Factors and Etiology of
      Diarrheal Disease among Children Aged 0-59 Months Seeking Care at Health
      Facilities.
AB  - BACKGROUND: Diarrheal disease remains a leading cause of illness and death,
      particularly in low-income countries. Its burden, microbiological causes and risk
      factors were examined in children aged 0-59 months living in Manhica, rural
      southern Mozambique. METHODS: Trends of diarrhea-related burden of disease were
      estimated during the period 2001-2012. A prospective, age-stratified and matched
      (by age, gender and geographical origin), case-control study was conducted during
      2007-2011. Clinical, epidemiology, anthropometric measurement and fecal samples
      obtained from recruited children were used to estimate moderate-to-severe
      diarrhea (MSD) weighted attributable fractions. RESULTS: Over the last decade the
      incidence of acute diarrhea has dropped by about 80%. Incidence of MSD per 100
      child years at risk for the period 2007-2011 was 9.85, 7.73 and 2.10 for children
      aged 0-11, 12-23 and 24-59 months respectively. By adjusted population
      attributable fractions, most cases of MSD were due to rotavirus, Cryptosporidium,
      ETEC ST (ST only or ST/LT), Shigella and Adenovirus 40/41. Washing hands and
      having facilities to dispose child's stools were associated with a reduced risk
      of MSD, while giving stored water to the child was associated with an increased
      risk of MSD. CONCLUSIONS: Despite the predominantly decreasing trends observed
      throughout the last decade, diarrheal diseases remain today a major cause of
      morbidity among children aged 0-59 months living in this rural Mozambican area.
      Rotavirus, cryptosporidium, Shigella, ETEC ST and Adenovirus 40/41 were the most
      important aetiologies of MSD. Thus, well-known preventive strategies such as
      washing hands, improving the treatment of stored water, having facilities to
      dispose children stools, and accelerating the introduction of the rotavirus
      vaccine should be promoted on a wider scale to reduce the current burden of
      diarrheal diseases.

PMID- 25973881
TI  - Morphometric and quantitative immunohistochemical analysis of disease-related
      changes in the upper (suburothelial) lamina propria of the human bladder dome.
AB  - The upper (suburothelial) lamina propria (ULP) is a distinct region in the human
      bladder with dense populations of interstitial cells (IC), fine vascular networks
      and variable development of muscularis mucosae (MM). It is more and more obvious
      that the ULP plays an important role in bladder physiology and bladder disease,
      and in the present study we have quantified changes in the cellular key players
      of the ULP in bladders from patients with carcinoma in situ (CIS), multiple
      sclerosis (MS) and bladder pain syndrome (BPS). Tissue samples for the different
      patient groups were obtained from radical cystectomy-specimens. Standardized
      immunohistochemistry with a panel of specific cell markers was used to
      characterise the ULP cellular structures, followed by digitalised morphometry and
      quantitative staining analysis. Alterations in the ULP area were most pronounced
      in MS bladders, but also present in BPS and CIS bladders. We observed an
      increased thickness and increased variability in thickness of the ULP IC area in
      MS and BPS bladders; a significantly increased development of MM in MS bladders;
      a changed organization of vascular plexuses in the lamina propria in most
      pathologic bladders and a changed phenotype of ULP IC: a significantly decreased
      expression of progesterone receptor in MS bladders and a trend towards decreased
      expression of alpha-smooth muscle actin in BPS bladders. We show here for the
      first time the presence of disease-specific changes in organisation and/or
      phenotype of the different key players of the ULP area in human bladder. The
      present findings further support the hypothesis that the ULP area is involved and
      altered in different bladder diseases. 

PMID- 25973882
TI  - Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of
      Observational Studies.
AB  - OBJECTIVE: The purpose of this paper is to examine cancer incidence in patients
      with ANCA-associated vasculitis (AASV) derived from population-based cohort
      studies by means of meta-analysis. METHODS: Relevant electronic databases were
      searched for studies characterizing the associated risk of overall malignancy in
      patients with AASV. Standardized incidence rates (SIRs) with 95% confidence
      intervals (CIs) were used to evaluate the strength of association. We tested for
      publication bias and heterogeneity and stratified for site-specific cancers.
      RESULTS: Six studies (n = 2,578) were eventually identified, of which six
      provided the SIR for overall malignancy, five reported the SIR for non-melanoma
      skin cancer (NMSC), four for leukemia, five for bladder cancer, three for
      lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer,
      four for prostate cancer, four for colon cancer and four for breast cancer.
      Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37-2.21),
      with moderate heterogeneity among these studies (I(2) = 65.8%, P = 0.012). In sub
      analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more
      frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47-7.73),
      4.89 (95%CI = 2.93-8.16) and 3.84 (95%CI = 2.72-5.42) respectively. There was no
      significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66
      6.85), prostate cancer (SIR = 1.45, 95%CI = 0.87-2.42), colon cancer (SIR = 1.26,
      95%CI = 0.70-2.27), and breast cancer (SIR = 0.95, 95%CI = 0.50-1.79). Among
      these site-specific cancers, only NMSC showed moderate heterogeneity (I2 = 55.8%,
      P = 0.06). No publication bias was found by using the Begg's test and Egger's
      test. CONCLUSIONS: This meta-analysis shows that AASV patients treatment with
      cyclophosphamide (CYC) are at increased risk of late-occurring malignancies,
      particularly of the NMSC, leukemia and bladder cancer. However, there is no
      significant association between AASV and kidney cancer, prostate cancer, colon
      cancer and breast cancer. These findings emphasize monitoring and preventative
      management in AASV patients after cessation of CYC therapy is momentous.

PMID- 25973883
TI  - Efficacy of a medical genetics rotation during pediatric training.
AB  - PURPOSE: With the greater understanding that genetics underlies the basis of
      health and disease, the practice of medicine is changing such that we are now in
      an era of genomic medicine. However, there has been a deficiency of training in
      genetics and genomics among primary care residents. METHODS: We describe the
      experience of our institution, which requires pediatric, child neurology, and
      medicine-pediatric residents to complete a subspecialty rotation in medical
      genetics. Standardized end-of-rotation evaluation results were analyzed and
      thematic analysis was performed. RESULTS: The mean overall educational quality of
      the rotation rated on a 5-point scale ranging from 1 (poor) to 5 (excellent) was
      4.49. The participation in medical genetics had three main outcomes: (i) a
      variety of learning opportunities were presented such that it was one of the most
      educational rotations that trainees experienced; (ii) both trainee competence and
      confidence in clinical practice improved through knowledge gained; and (iii) an
      increased awareness and appreciation for interprofessional relationships,
      especially for the genetic counseling profession, was highly valued. In addition,
      some residents have gone on to choose medical genetics as a profession.
      CONCLUSION: A rotation in medical genetics increases knowledge and awareness of
      the importance that medical genetics has in clinical practice.

PMID- 25973884
TI  - Non-Invasive Genetic Mark-Recapture as a Means to Study Population Sizes and
      Marking Behaviour of the Elusive Eurasian Otter (Lutra lutra).
AB  - Quantifying population status is a key objective in many ecological studies, but
      is often difficult to achieve for cryptic or elusive species. Here, non-invasive
      genetic capture-mark-recapture (CMR) methods have become a very important tool to
      estimate population parameters, such as population size and sex ratio. The
      Eurasian otter (Lutra lutra) is such an elusive species of management concern and
      is increasingly studied using faecal-based genetic sampling. For unbiased sex
      ratios or population size estimates, the marking behaviour of otters has to be
      taken into account. Using 2132 otter faeces of a wild otter population in Upper
      Lusatia (Saxony, Germany) collected over six years (2006-2012), we studied the
      marking behaviour and applied closed population CMR models accounting for genetic
      misidentification to estimate population sizes and sex ratios. We detected a sex
      difference in the marking behaviour of otters with jelly samples being more often
      defecated by males and placed actively exposed on frequently used marking sites.
      Since jelly samples are of higher DNA quality, it is important to not only
      concentrate on this kind of samples or marking sites and to invest in
      sufficiently high numbers of repetitions of non-jelly samples to ensure an
      unbiased sex ratio. Furthermore, otters seemed to increase marking intensity due
      to the handling of their spraints, hence accounting for this behavioural response
      could be important. We provided the first precise population size estimate with
      confidence intervals for Upper Lusatia (for 2012: N = 20 +/- 2.1, 95% CI = 16-25)
      and showed that spraint densities are not a reliable index for abundances. We
      further demonstrated that when minks live in sympatry with otters and have
      comparably high densities, a non-negligible number of supposed otter samples are
      actually of mink origin. This could severely bias results of otter monitoring if
      samples are not genetically identified.

PMID- 25973885
TI  - Practical continuous-flow trapping metalations of functionalized arenes and
      heteroarenes using TMPLi in the presence of Mg, Zn, Cu, or La halides.
AB  - The flow metalation of various arenes and heteroarenes involving an in situ
      trapping with metal salts (ZnCl2 ?2 LiCl, MgCl2 , CuCN?2 LiCl, LaCl3 ?2 LiCl)
      under very convenient conditions (0  degrees C, 40 s) is reported. The resulting
      Mg, Zn, Cu, or La organic species are trapped with various electrophiles in high
      yields. In several cases, unusual kinetically controlled regioselectivities are
      obtained. All these flow metalations can be scaled up simply by extending the
      reaction time and without further optimization. The reaction scope of such flow
      metalations is considerably broader than that of the corresponding batch
      procedures. 

PMID- 25973886
TI  - Keeping in shape the dogma of mitochondrial DNA maternal inheritance.

PMID- 25973887
TI  - Surgical Interventions for Pediatric Unilateral Vocal Cord Paralysis: A
      Systematic Review.
AB  - IMPORTANCE: The most widely used surgical interventions for pediatric unilateral
      vocal cord paralysis include injection laryngoplasty, thyroplasty, and laryngeal
      reinnervation. Despite increasing interest in surgical interventions for
      unilateral vocal cord paralysis in children, the surgical outcomes data in
      children are scarce. OBJECTIVE: To appraise and summarize the available evidence
      for pediatric unilateral vocal cord paralysis surgical strategies. EVIDENCE
      REVIEW: MEDLINE (1946-2014) and EMBASE (1980-2014) were searched for publications
      that described the results of laryngoplasty, thyroplasty, or laryngeal
      reinnervation for pediatric unilateral vocal cord paralysis. Further studies were
      identified from bibliographies of relevant studies, gray literature, and annual
      scientific assemblies. Two reviewers independently appraised the selected studies
      for quality, level of evidence, and risk of bias as well as extracted data,
      including unilateral vocal cord paralysis origin, voice outcomes, swallowing
      outcomes, and adverse events. FINDINGS: Of 366 identified studies, the inclusion
      criteria were met by 15 studies: 6 observational studies, 6 case series, and 3
      case reports. All 36 children undergoing laryngeal reinnervation (8 studies) had
      improvement or resolution of dysphonia. Of 31 children receiving injection
      laryngoplasty (6 studies), most experienced improvement in voice quality, speech,
      swallowing, aspiration, and glottic closure. Of 12 children treated by
      thyroplasty (5 studies), 2 experienced resolution of dysphonia, 4 had some
      improvement, and 4 had no improvement (2 patients had undocumented outcomes).
      Thyroplasty resolved or improved aspiration in 7 of 8 patients. CONCLUSIONS AND
      RELEVANCE: Published studies suggest that reinnervation may be the most effective
      surgical intervention for children with dysphonia; however, long-term follow-up
      data are lacking. With the exception of polytetrafluoroethylene injections,
      injection laryngoplasty was reported to be a relatively safe, nonpermanent, and
      effective option for most children with dysphonia. Thyroplasty appears to have
      fallen out favor in recent years because of difficulty in performing this
      procedure in children under local anesthesia, but it continues to be a viable
      option for children with aspiration.

PMID- 25973888
TI  - Formation of Monocrystalline 1D and 2D Architectures via Epitaxial Attachment:
      Bottom-Up Routes through Surfactant-Mediated Arrays of Oriented Nanocrystals.
AB  - Monocrystalline architectures with well-defined shapes were achieved by bottom-up
      routes through epitaxial attachment of Mn3O4 nanocrystals. The
      crystallographically continuous 1D chains elongated in the a axis and 2D panels
      having large a or c faces were obtained by removal of the organic mediator from
      surfactant-mediated 1D and 2D arrays of Mn3O4 nanocrystals, respectively. Our
      basal approach indicates that the epitaxial attachment through the surfactant
      mediated arrays is utilized for fabrication of a wide variety of micrometric
      architectures from nanometric crystalline units. 

PMID- 25973890
TI  - Abstracts of the 1st Congress of Physiology and Integrative Biology (CPBI) and
      84th Congress of French Physiological Society (SFP), 4-6 May 2015, Strasbourg,
      France.

PMID- 25973889
TI  - Beneficial Effects of Polyphenol-Rich Chokeberry Juice Consumption on Blood
      Pressure Level and Lipid Status in Hypertensive Subjects.
AB  - Epidemiological studies have shown a positive association between intake of foods
      rich in antioxidants and lower incidence of cardiovascular disease development.
      Polyphenols are considered the most abundant and important dietary antioxidants.
      The aim of this study was to evaluate effects of polyphenol-rich chokeberry juice
      consumption on 24-h ambulatory monitored blood pressure (BP) level in subjects
      with no pharmacologically treated high normal BP or grade I hypertension. Twenty
      three subjects (12 men and 11 women) aged 33-67 were enrolled and instructed to
      consume 200 mL of juice daily for 4 weeks. Participants were divided in two
      groups, based on prevalence of sympathetic or parasympathetic activity.
      Measurements of biochemical parameters and heart rate variability analysis were
      also applied. At the end of the intervention period, average 24-h and awake
      systolic and diastolic BP were significantly decreased (P<.05). This was more
      pronounced in the group with prevalence of sympathetic activity. Significant
      reduction in triglyceride level (P<.05) and a reducing effect on total and low
      density lipoprotein cholesterol were also found. Obtained results indicate a
      positive impact of regular chokeberry juice consumption on BP and lipid status in
      pharmacologically untreated hypertensive subjects.

PMID- 25973891
TI  - Gene expression and functional analyses in brassinosteroid-mediated stress
      tolerance.
AB  - The plant hormone brassinosteroid (BR) plays essential roles in plant growth and
      development, while also controlling plant stress responses. This dual ability of
      BR is intriguing from a mechanistic point of view and as a viable solution for
      stabilizing crop yields under the changing climatic conditions. Here we report a
      time course analysis of BR responses under both stress and no-stress conditions,
      the results of which establish that BR incorporates many stress-related features
      even under no-stress conditions, which are then accompanied by a dynamic stress
      response under unfavourable conditions. Found within the BR transcriptome were
      distinct molecular signatures of two stress hormones, abscisic acid and jasmonic
      acid, which were correlated with enhanced endogenous levels of the two hormones
      in BR-treated seedlings. The marked presence of genes related to protein
      metabolism and modification, defence responses and calcium signalling highlights
      the significance of their associated mechanisms and roles in BR processes.
      Functional analysis of loss-of-function mutants of a subset of genes selected
      from the BR transcriptome identified abiotic stress-related roles for ACID
      PHOSPHATASE5 (ACP5), WRKY33, JACALIN-RELATED LECTIN1-3 (JAC-LEC1-3) and a BR
      RESPONSIVE-RECEPTOR-LIKE KINASE (BRRLK). Overall, the results of this study
      provide a clear link between the molecular changes impacted by BR and its ability
      to confer broad-range stress tolerance, emphasize the importance of post
      translational modification and protein turnover as BR regulatory mechanisms and
      demonstrate the BR transcriptome as a repertoire of new stress-related regulatory
      and structural genes. 

PMID- 25973892
TI  - Divergent Method to trans-5-Hydroxy-6-alkynyl/alkenyl-2-piperidinones: Syntheses
      of (-)-Epiquinamide and (+)-Swainsonine.
AB  - An efficient diastereoselective approach to access trans-5-hydroxy-6
      alkynyl/alkenyl-2-piperidinones has been developed through nucleophilic addition
      of alpha-chiral aldimines using alkynyl/alkenyl Grignard reagents. The
      diastereoselectivity of alkenyl in C-6 position of 2-piperidinone was controlled
      by alpha-alkoxy substitution, while the alkynyl was controlled by the
      coordination of the alpha-alkoxy substitution and stereochemistry of sulfinamide.
      The utility of this straightforward cascade process is demonstrated by the
      asymmetric synthesis of the (-)-epiquinamide and (+)-swainsonine. 

PMID- 25973895
TI  - A reliable parameter to standardize the scoring of stem cell spheres.
AB  - Sphere formation assay is widely used in selection and enrichment of normal stem
      cells or cancer stem cells (CSCs), also known as tumor initiating cells (TICs),
      based on their ability to grow in serum-free suspension culture for clonal
      proliferation. However, there is no standardized parameter to accurately score
      the spheres, which should be reflected by both the number and size of the
      spheres. Here we define a novel parameter, designated as Standardized Sphere
      Score (SSS), which is expressed by the total volume of selected spheres divided
      by the number of cells initially plated. SSS was validated in quantification of
      both tumor spheres from cancer cell lines and embryonic bodies (EB) from mouse
      embryonic stem cells with high sensitivity and reproducibility. 

PMID- 25973893
TI  - Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood
      Mononuclear Cells from Patients with IgG4-Related Disease.
AB  - BACKGROUND: IgG4-related disease (IgG4-RD) is a new clinical entity of unknown
      etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4
      positive plasma cells. Although aberrancies in acquired immune system functions,
      including increases in Th2 and Treg cytokines observed in patients with IgG4-RD,
      its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD,
      this study compared the expression of genes related to innate immunity in
      patients with IgG4-RD and healthy controls. MATERIALS AND METHODS: Peripheral
      blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before
      and after steroid therapy and from healthy controls. Total RNA was extracted and
      DNA microarray analysis was performed in two IgG4-RD patients to screen for genes
      showing changes in expression. Candidate genes were validated by real-time RT-PCR
      in 27 patients with IgG4-RD and 13 healthy controls. RESULTS: DNA microarray
      analysis identified 21 genes that showed a greater than 3-fold difference in
      expression between IgG4-RD patients and healthy controls and 30 genes that showed
      a greater than 3-fold change in IgG4-RD patients following steroid therapy.
      Candidate genes related to innate immunity, including those encoding Charcot
      Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3
      (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were
      validated by real-time RT-PCR. Expression of all genes was significantly lower in
      IgG4-RD patients than in healthy controls. Steroid therapy significantly
      increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the
      expression of CLC, IL8RA and IL8RB. CONCLUSIONS: The expression of genes related
      to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and
      IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls.
      Although there is the limitation in the number of patients applied in DNA
      microarray, impaired expression of genes related to innate immunity may be
      involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired
      immunity.

PMID- 25973894
TI  - Comparative evaluation of nephrotoxicity and management by macrophages of
      intravenous pharmaceutical iron formulations.
AB  - BACKGROUND: There is a significant clinical need for effective treatment of iron
      deficiency. A number of compounds that can be administered intravenously have
      been developed. This study examines how the compounds are handled by macrophages
      and their relative potential to provoke oxidative stress. METHODS: Human kidney
      (HK-2) cells, rat peritoneal macrophages and renal cortical homogenates were
      exposed to pharmaceutical iron preparations. Analyses were performed for indices
      of oxidative stress and cell integrity. In addition, in macrophages, iron uptake
      and release and cytokine secretion was monitored. RESULTS: HK-2 cell viability
      was decreased by iron isomaltoside and ferumoxytol and all compounds induced
      lipid peroxidation. In the renal cortical homogenates, lipid peroxidation
      occurred at lowest concentrations with ferric carboxymaltose, iron dextran, iron
      sucrose and sodium ferric gluconate. In the macrophages, iron sucrose caused loss
      of cell viability. Iron uptake was highest for ferumoxytol and iron isomaltoside
      and lowest for iron sucrose and sodium ferric gluconate. Iron was released as
      secretion of ferritin or as ferrous iron via ferroportin. The latter was blocked
      by hepcidin. Exposure to ferric carboxymaltose and iron dextran resulted in
      release of tumor necrosis factor alpha. CONCLUSIONS: Exposure to iron compounds
      increased cell stress but was tissue and dose dependent. There was a clear
      difference in the handling of iron from the different compounds by macrophages
      that suggests in vivo responses may differ.

PMID- 25973897
TI  - Periconceptional Multivitamin Supplementation Containing Folic Acid and Sex Ratio
      at Birth in a Chinese Population: a Prospective Cohort Study.
AB  - BACKGROUND: To determine whether periconceptional use of multivitamin supplements
      containing folic acid increases the occurrence of male births in a Chinese
      population. METHODS: A prospective cohort study was carried out in 18 counties in
      four provinces of China. Participants were naturally and voluntarily divided into
      an intervention group (who took a multivitamin pill containing folic acid, n =
      25,418) and a control group (who did not take any multivitamin, n = 26,580).
      Multivitamin supplements containing folic acid was ascertained before pregnancy.
      Pregnant women were followed through the first trimester of pregnancy and the
      outcome of pregnancy (i.e. livebirth, stillbirth, or fetal death; sex at birth)
      was recorded. RESULTS: A total of 52,043 pregnancies and 51,998 births were
      recorded between September 2000 and August 2002. The proportion of males born to
      women who did and did not take the multivitamin were 54.8% (n = 13,935) and 54.0%
      (n = 11,483), respectively. The male to female sex ratios at birth among women
      who did and did not take the multivitamin were 117:100 and 121:100, respectively.
      The risk ratio was 1.03 [95% confidence interval 0.99, 1.06] after adjusting for
      confounding factors. CONCLUSIONS: These findings suggest that periconceptional
      multivitamin supplementation containing folic acid is not associated with an
      increased likelihood of male births in a Chinese population. However, these
      results may have been affected by induced abortion or selective termination of
      pregnancy, and the findings must therefore be cautiously interpreted.

PMID- 25973896
TI  - Models of Postural Control: Shared Variance in Joint and COM Motions.
AB  - This paper investigated the organization of the postural control system in human
      upright stance. To this aim the shared variance between joint and 3D total body
      center of mass (COM) motions was analyzed using multivariate canonical
      correlation analysis (CCA). The CCA was performed as a function of established
      models of postural control that varied in their joint degrees of freedom (DOF),
      namely, an inverted pendulum ankle model (2DOF), ankle-hip model (4DOF), ankle
      knee-hip model (5DOF), and ankle-knee-hip-neck model (7DOF). Healthy young adults
      performed various postural tasks (two-leg and one-leg quiet stances, voluntary AP
      and ML sway) on a foam and rigid surface of support. Based on CCA model selection
      procedures, the amount of shared variance between joint and 3D COM motions and
      the cross-loading patterns we provide direct evidence of the contribution of
      multi-DOF postural control mechanisms to human balance. The direct model fitting
      of CCA showed that incrementing the DOFs in the model through to 7DOF was
      associated with progressively enhanced shared variance with COM motion. In the
      7DOF model, the first canonical function revealed more active involvement of all
      joints during more challenging one leg stances and dynamic posture tasks.
      Furthermore, the shared variance was enhanced during the dynamic posture
      conditions, consistent with a reduction of dimension. This set of outcomes shows
      directly the degeneracy of multivariate joint regulation in postural control that
      is influenced by stance and surface of support conditions. 

PMID- 25973898
TI  - 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone
      Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice.
AB  - Starting off with a structure derived from the natural compound multiflorine, a
      derivatisation program aimed at the discovery and initial characterisation of
      novel compounds with antidiabetic potential. Design and discovery of the
      structures was guided by oral bioactivities obtained in oral glucose tolerance
      tests in mice. 55P0110, one among several new compounds with distinct anti
      hyperglycaemic activity, was further examined to characterise its pharmacology
      and mode of action. Whereas a single oral dose of 55P0110 did not affect basal
      glycaemia, it markedly improved the glucose tolerance of healthy and diabetic
      mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90
      mg/kg 55P0110, 17.0 +/- 1.2 vs. 10.1 +/- 1.1; diabetic mice with 180 mg/kg
      55P0110, 23.1 +/- 0.9 vs. 11.1 +/- 1.4; p<0.001 each). Closer examination argued
      against retarded glucose resorption from the gut, increased glucose excretion in
      urine, acute insulin-like or insulin sensitising properties, and direct
      inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence,
      55P0110 seems to act via a target not exploited by any drug presently approved
      for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea
      gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose
      ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min.
      after dosing, nmol/mol: vehicle, 2.49 +/- 0.27; 55P0110, 2.99 +/- 0.35;
      gliclazide, 8.97 +/- 0.49; p<0.001 each vs. gliclazide). Under an exogenous
      glucose challenge, however, 55P0110 increased this ratio to the same extent as
      gliclazide (20 min. after glucose feeding: vehicle, 2.53 +/- 0.41; 55P0110, 3.80
      +/- 0.46; gliclazide, 3.99 +/- 0.26; p<0.05 each vs. vehicle). By augmenting the
      glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti
      hyperglycaemic action in combination with low risk for fasting hypoglycaemia in
      mice. In summary, we have discovered a novel class of fully synthetic substituted
      quinazolidines with an attractive pharmacological profile that recommends the
      structures for further evaluation as candidates for the treatment of diabetes
      mellitus.

PMID- 25973899
TI  - Dust devil: the life and times of the fungus that causes valley Fever.

PMID- 25973900
TI  - Integrin alpha4 Enhances Metastasis and May Be Associated with Poor Prognosis in
      MYCN-low Neuroblastoma.
AB  - High-risk neuroblastoma is associated with an overall survival rate of 30-50%.
      Neuroblastoma-expressed cell adhesion receptors of the integrin family impact
      cell adhesion, migration, proliferation and survival. Integrin alpha4 is
      essential for neural crest cell motility during development, is highly expressed
      on leukocytes, and is critical for transendothelial migration. Thus, cancer cells
      that express this receptor may exhibit increased metastatic potential. We show
      that alpha4 expression in human and murine neuroblastoma cell lines selectively
      enhances in vitro interaction with the alternatively spliced connecting segment 1
      of fibronectin, as well as vascular cell adhesion molecule-1 and increases
      migration. Integrin alpha4 expression enhanced experimental metastasis in a
      syngeneic tumor model, reconstituting a pattern of organ involvement similar to
      that seen in patients. Accordingly, antagonism of integrin alpha4 blocked
      metastasis, suggesting adhesive function of the integrin is required. However,
      adhesive function was not sufficient, as mutants of integrin alpha4 that
      conserved the matrix-adhesive and promigratory function in vitro were compromised
      in their metastatic capacity in vivo. Clinically, integrin alpha4 is more
      frequently expressed in non-MYNC amplified tumors, and is selectively associated
      with poor prognosis in this subset of disease. These results reveal an unexpected
      role for integrin alpha4 in neuroblastoma dissemination and identify alpha4 as a
      potential prognostic indicator and therapeutic target. 

PMID- 25973902
TI  - Sex pheromones and reproductive isolation in five mirid species.
AB  - Mate location in many mirid bugs (Heteroptera: Miridae) is mediated by female
      released sex pheromones. To elucidate the potential role of the pheromones in
      prezygotic reproductive isolation between sympatric species, we investigated
      differences in the pheromone systems of five mirid species, Apolygus lucorum,
      Apolygus spinolae, Orthops campestris, Stenotus rubrovittatus and Taylorilygus
      apicalis. GC/MS analyses of metathoracic scent gland extracts of virgin females
      showed that all five species produced mixtures of hexyl butyrate, (E)-2-hexenyl
      butyrate and (E)-4-oxo-2-hexenal, but in quite different ratios. (E)-2-hexenyl
      butyrate was the major component of A. spinolae, while hexyl butyrate was the
      most abundant component in the pheromone blends of the other four species. In
      addition to the three compounds, a fourth component, (E)-2-octenyl butyrate, was
      present in the gland extracts of A. lucorum and T. apicalis females. Field tests
      suggest that the ternary blends of hexyl butyrate, (E)-2-hexenyl butyrate and (E)
      4-oxo-2-hexenal as found in the extracts of the females of each species do not
      inhibit attraction of conspecific males but ensure species-specificity of
      attraction between A. lucorum, O. campestris and T. apicalis. Furthermore, (E)-2
      octenyl butyrate was essential for attraction of A. lucorum and T. apicalis
      males, but strongly inhibited attraction of male A. spinolae, O. campestris and
      S. rubrovittatus. The combined results from this study and previous studies
      suggest that the minor component and pheromone dose in addition to the relative
      ratio of the major components play an important role in reproductive isolation
      between mirid species. 

PMID- 25973901
TI  - Changes in transcriptome of macrophages in atherosclerosis.
AB  - Macrophages display significant phenotypic heterogeneity. Two growth factors,
      macrophage colony-stimulating factor and chemokine (C-X-C motif) ligand 4, drive
      terminal differentiation of monocytes to M0 and M4 macrophages respectively.
      Compared to M0 macrophages, M4 cells have a unique transcriptome, with expression
      of surface markers such as S100A8, mannose receptor CD206 and matrix
      metalloproteinase 7. M4 macrophages did not express CD163, a scavenger receptor
      for haemoglobin/haptoglobin complex. Depending on the stimuli, M0 macrophages
      could polarize towards the proinflammatory M1 subset by treatment with
      lipopolysaccharide or interferon-gamma. These macrophages produce a range of
      proinflammatory cytokines, nitric oxide, reactive oxygen species and exhibit high
      chemotactic and phagocytic activity. The alternative M2 type could be induced
      from M0 macrophage by stimulation with interleukin (IL)-4. M2 macrophages express
      high levels of CD206 and produce anti-inflammatory cytokines IL-10 and
      transforming growth factor-beta. M1, M2 and M4 macrophages could be found in
      atherosclerotic plaques. In the plaque, macrophages are subjected to the
      intensive influence not only by cytokines and chemokines but also with bioactive
      lipids such as cholesterol and oxidized phospholipids. Oxidized phospholipids
      induce a distinct Mox phenotype in murine macrophages that express a unique panel
      of antioxidant enzymes under control of the redox-regulated transcription factor
      Klf2, resistant to lipid accumulation. In unstable human lesions,
      atheroprotective M(Hb) and HA-mac macrophage subsets could be found. These two
      subsets are induced by the haemoglobin/haptoglobin complex, highly express haeme
      oxygenase 1 and CD163, and are implicated in clearance of haemoglobin and
      erythrocyte remnants. In atherogenesis, the macrophage phenotype is plastic and
      could therefore be switched to proinflammatory (i.e. proatherogenic) and anti
      inflammatory (i.e. atheroprotective). The aim of this review was to characterize
      changes in macrophage transcriptome in atherosclerosis and discuss key markers
      that characterize different phenotypes of macrophages present in atherosclerotic
      lesions. 

PMID- 25973903
TI  - Access to orphan drugs in western Europe: can more systematic policymaking really
      help to avoid different decisions about the same drug?
AB  - When the Scottish government recently launched a L21 million fund to provide
      patients with rare diseases access to treatment, Alex Neill, the Scottish Health
      Secretary, stated that 'it was only right that Scottish patients with rare
      conditions had access to innovative medicines which were clinically justified,
      and that they were not disadvantaged due to the very high cost of these
      treatments'. This statement raises questions about the criteria that play a role
      in reimbursement decisions on orphan drugs. This editorial examines the criteria
      that were used in the decisions about the reimbursement of an orphan drug for
      Pompe disease and explores methods to improve the transparency and consistency of
      reimbursement decisions for orphan drugs in general. 

PMID- 25973904
TI  - Study on the inter- and intra-peptide salt-bridge mechanism of Abeta23-28
      oligomer interaction with small molecules: QM/MM method.
AB  - Amyloid beta (Abeta) peptides have long been known to be a potential candidate
      for the onset of Alzheimer's disease (AD). The biophysical properties of Abeta42
      peptide aggregates are of significant importance for the amyloid cascade
      mechanism of AD. It is necessary to design an inhibitor using small molecules to
      reduce the aggregation process in Abeta42 peptides. Attention has been given to
      use the natural products as anti-aggregation compounds, directly targeting Abeta
      peptides. Polyphenols have been extensively studied as a class of amyloid
      inhibitors. 9,10-Anthraquinone (AQ) is present in abundance in medicinal plants
      (rhubarb), the Trp-Pro-Tyr (TPT) peptide has been found in the venom of the black
      mamba snake, and the morin molecule is naturally present in wine and green tea;
      several other polyphenol derivatives are under clinical trials to develop anti
      neurodegenerative drugs. In vitro and in vivo results strongly suggest that AQ
      and morin molecules are potential inhibitors of Abeta aggregation; however, the
      detailed understanding of the inhibition mechanism remains largely unknown. The
      formation of Abeta fibrils and oligomers requires a conformational change from
      alpha-helix to beta-sheet, which occurs due to the formation of a salt-bridge
      between Asp(23) and Lys(28) residues. The present study focused on investigating
      the salt-bridge mechanism in the monomer, dimer and oligomer of the Abeta23-28
      peptide during the interaction with TPT, morin and AQ molecules. Interaction
      energy and natural bond orbital analyses have been carried out using the
      ONIOM(M05-2X/6-31++G(d,p):UFF) method. The QM/MM studies have been performed to
      study the mechanism of salt-bridge formation during the inhibition process of
      amyloid beta protein aggregation. The TPT molecule, which binds with the Asp(23)
      and Lys(28) residues of Abeta, prevents the salt-bridge formation between Asp(23)
      and Lys(28) residues and consequently the probability of the formation of Abeta
      fibrils is reduced. 

PMID- 25973905
TI  - High Risk of Hepatitis B Reactivation among Patients with Acute Myeloid Leukemia.
AB  - BACKGROUND: Hepatitis B virus (HBV) infections are common and associated with
      significant morbidity and mortality in cancer patients. However, the incidence
      and risk factors of HBV reactivation in patients with acute myeloid leukemia
      (AML) are rarely investigated. METHODS: AML patients followed-up at the National
      Taiwan University Hospital between 2006 and 2012 were analyzed. The clinical
      characteristics and laboratory data were retrospectively reviewed. RESULTS: Four
      hundred and ninety patients comprising 265 men and 225 women were studied. The
      median age was 52 years (range, 18 - 94). Chronic HBV carriage was documented at
      the time of leukemia diagnosis in 57 (11.6%) patients. Forty-six (80.7%) of the
      57 HBV carriers received prophylaxis with anti-HBV agents. Sixteen HBV carriers
      (28.1%) developed hepatitis B reactivation during or after chemotherapy,
      including 7 patients who had discontinued antiviral therapy. The incidence of
      hepatitis B reactivation among AML patients with HBV carriage was 9.5 per 100
      person-years. Prophylaxis with anti-HBV agents significantly decreased the risk
      of hepatitis B reactivation among HBV carriers (13% vs. 61%, p<0.001). Four
      (2.8%) of 142 patients with initial positive anti-HBsAb and anti-HBcAb
      experienced hepatitis B reactivation and lost their protective anti-HBsAb.
      Multivariate analysis revealed that diabetes mellitus (p=0.008, odds ratio (OR) =
      2.841, 95% confident interval (CI): 0.985-8.193) and carriage of HBsAg (p<0.001,
      OR=36.878, 95% CI: 11.770-115.547) were independent risk factors for hepatitis B
      reactivation in AML patients. CONCLUSIONS: Hepatitis B reactivation is not
      uncommon in the HBsAg positive AML patients. Prophylaxis with anti-HBV agent
      significantly decreased the risk of hepatitis B reactivation.

PMID- 25973906
TI  - A Split-and-Merge-Based Uterine Fibroid Ultrasound Image Segmentation Method in
      HIFU Therapy.
AB  - High-intensity focused ultrasound (HIFU) therapy has been used to treat uterine
      fibroids widely and successfully. Uterine fibroid segmentation plays an important
      role in positioning the target region for HIFU therapy. Presently, it is
      completed by physicians manually, reducing the efficiency of therapy. Thus,
      computer-aided segmentation of uterine fibroids benefits the improvement of
      therapy efficiency. Recently, most computer-aided ultrasound segmentation methods
      have been based on the framework of contour evolution, such as snakes and level
      sets. These methods can achieve good performance, although they need an initial
      contour that influences segmentation results. It is difficult to obtain the
      initial contour automatically; thus, the initial contour is always obtained
      manually in many segmentation methods. A split-and-merge-based uterine fibroid
      segmentation method, which needs no initial contour to ensure less manual
      intervention, is proposed in this paper. The method first splits the image into
      many small homogeneous regions called superpixels. A new feature representation
      method based on texture histogram is employed to characterize each superpixel.
      Next, the superpixels are merged according to their similarities, which are
      measured by integrating their Quadratic-Chi texture histogram distances with
      their space adjacency. Multi-way Ncut is used as the merging criterion, and an
      adaptive scheme is incorporated to decrease manual intervention further. The
      method is implemented using Matlab on a personal computer (PC) platform with
      Intel Pentium Dual-Core CPU E5700. The method is validated on forty-two
      ultrasound images acquired from HIFU therapy. The average running time is 9.54 s.
      Statistical results showed that SI reaches a value as high as 87.58%, and normHD
      is 5.18% on average. It has been demonstrated that the proposed method is
      appropriate for segmentation of uterine fibroids in HIFU pre-treatment imaging
      and planning.

PMID- 25973907
TI  - Young, Online and in the Dark: Scaling Up HIV Testing among MSM in ASEAN.
AB  - BACKGROUND: Poor HIV testing uptake by MSM may be attributable to unique
      challenges that are localized in Southeast Asia. OBJECTIVE: To characterize MSM
      who never tested for HIV, to identify correlates of never testing, and to
      elucidate the perceived barriers to HIV testing. METHODS: The present study used
      data from the Asian Internet MSM Sex Survey (AIMSS) and restricted the analysis
      to 4,310 MSM from the ten member countries of the Association of South East Asian
      Nations (ASEAN). RESULTS: Among MSM participants from ASEAN in our sample, 1290
      (29.9%) reported having never been tested for HIV, 471 (10.9%) tested for HIV
      more than 2 years ago, and 2186 (50.7%) reported their last test date was between
      6 months and two years ago, with only 363 (8.4%) of these men having been tested
      in the past 6 months. In multivariable logistic regression, younger MSM (age 15
      22 years old [AOR: 4.60, 95% CI: 3.04-6.96]), MSM with lower education (secondary
      school or lower [AOR: 1.37, 95% CI: 1.03-1.83]), MSM who identify as bisexual or
      heterosexual (compared to gay-identified) (AOR: 1.94, 95% CI: 1.60-2.35), and MSM
      who had never used a condom with male partners (AOR: 1.61, 95% CI: 1.32-1.97) had
      higher odds of never been HIV tested. Main reason for not being tested was a low
      risk perception of HIV exposure (n = 390, 30.2%). CONCLUSION: Current HIV
      prevention response must not leave MSM "in the dark," but instead meet them where
      they are by utilizing the Internet creatively through social media and smart
      phones. As ASEAN Economic Community (AEC) is quickly becoming a reality, so must
      there be an equally fast and united response to slowing down the HIV epidemics
      among MSM in ASEAN.

PMID- 25973908
TI  - Perioperative management of 19 infants undergoing glossopexy (tongue-lip
      adhesion) procedure: a retrospective study.
AB  - BACKGROUND: Glossopexy (tongue-lip adhesion) is a procedure in which the tongue
      is anchored to the lower lip and mandible to relieve the upper airway obstruction
      mainly in infants with Pierre Robin sequence. Infants suffering from severe upper
      airway obstruction and feeding difficulties due to glossoptosis are the
      candidates for this procedure and are predicted to demonstrate difficult airway
      and difficult intubation. METHODS: We retrospectively examined the perioperative
      management of 19 infants undergoing glossopexy procedure at our institution from
      1992 to 2010. RESULTS: Out of 19 patients, Pierre Robin sequence was diagnosed in
      17, Treacher Collins syndrome in 1, and Stickler syndrome in 1. In all of them,
      inhalation anesthesia was induced with a nasopharyngeal tube in place. Nine
      patients underwent fiberoptic intubation. After surgery, 12 patients were
      extubated in the operating room and 11 of them required a nasopharyngeal tube to
      keep the airway open. Seven patients left the operating room with the trachea
      intubated. Two patients received tracheostomy at the age of 2 months. Seventeen
      patients underwent release of tongue-lip adhesion coincidentally with the palate
      repair at 7-14 months of age. For this surgery, no one required fiberoptic
      intubation. CONCLUSIONS: The airway of these patients should be managed carefully
      not only before but also after the operation. A nasopharyngeal tube was effective
      in maintaining the upper airway patency during anesthesia induction and before
      and after operation.

PMID- 25973909
TI  - Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT
      089 in mild to moderate Alzheimer disease.
AB  - ABT-089, an alpha4beta2 neuronal nicotinic receptor partial agonist, was
      evaluated for efficacy and safety in mild to moderate Alzheimer disease patients
      receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double
      blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively
      randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily)
      or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's
      Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian
      response-adaptive randomization algorithm dynamically assigned allocation
      probabilities based on interim ADAS-Cog total scores. A normal dynamic linear
      model for dose-response relationships and a longitudinal model for predicting
      final ADAS-cog score were employed in the algorithm. Stopping criteria for
      futility or success were defined. The futility stopping criterion was met,
      terminating the study with 337 patients randomized. No dose-response relationship
      was observed and no dose demonstrated statistically significant improvement over
      placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all
      dose levels. When administered as adjunctive therapy to acetylcholinesterase
      inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease.
      The adaptive study design enabled the examination of a broad dose range, enabled
      rapid determination of futility, and reduced patient exposure to nonefficacious
      doses of the investigational compound. 

PMID- 25973910
TI  - Does Alzheimer Disease Pathologic Change Underlie Subjective Cognitive
      Complaints?

PMID- 25973912
TI  - Geometric and Electronic Structures for MnS2(-/0) Clusters by Interpreting the
      Anion Photoelectron Spectrum with Quantum Chemical Calculations.
AB  - Geometric and electronic structures of linear SMnS, cyclic eta(2)-MnS2, and
      linear eta(1)-MnS2 isomers of MnS2(-) clusters have been investigated with B3LYP,
      CCSD(T), and NEVPT2 methods. The ground state of the anionic cluster is
      determined as (5)Pig of the linear SMnS(-) isomer, while the ground state of the
      neutral cluster may be either the (4)Sigmag(-) of the same isomer or the (6)A1 of
      the eta(2)-MnS2 cluster. The experimental photoelectron spectrum of the MnS2(-)
      cluster is interpreted by contributions of these two isomers. The high-intensity
      band at a binding energy of 2.94 eV is attributed to the (5)Pig -> (4)Sigmag(-)
      transition between the linear SMnS(-/0) clusters. The lower energy feature in the
      spectrum at binding energies between 1.9 and 2.8 eV and exhibiting a low
      intensity, is ascribed to electron detachments within the less stable eta(2)
      MnS2(-/0) clusters. Ionizations from the lowest energy (7)A1 state of this isomer
      to the neutral (6)A1, (6)A2, (8)A2, and (6)B2 states are responsible for this
      part of the spectrum. The extreme low intensity part between 1.3 and 1.9 eV can
      be due to excited states of either SMnS(-) or eta(2)-MnS2(-). 

PMID- 25973911
TI  - Early lineage priming by trisomy of Erg leads to myeloproliferation in a Down
      syndrome model.
AB  - Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human
      aneuploidy. Pre-leukemic myeloproliferative changes in DS foetal livers precede
      the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS
      TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is
      required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We
      demonstrate here that genetic changes specifically attributable to trisomy of Erg
      lead to lineage priming of primitive and early multipotential progenitor cells in
      Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant
      myeloproliferation. Gene expression changes dependent on trisomy of Erg in
      Ts(1716)65Dn multilineage progenitor cells were correlated with those associated
      with trisomy of HSA21 in human DS hematopoietic stem and primitive progenitor
      cells. These data suggest a role for ERG as a regulator of hematopoietic lineage
      potential, and that trisomy of ERG in the context of DS foetal liver hemopoiesis
      drives the pre-leukemic changes that predispose to subsequent DS-TMD and DS-AMKL.

PMID- 25973913
TI  - Pt/Ta2 O5 /HfO2- x /Ti resistive switching memory competing with multilevel NAND
      flash.
AB  - Pt/Ta2 O5 /HfO2- x /Ti resistive switching memory with a new circuit design is
      presented as a feasible candidate to succeed multilevel-cell (MLC) NAND flash
      memory. This device has the following characteristics: 3 bit MLC, electroforming
      free, self-rectifying, much higher cell resistance than interconnection wire
      resistance, low voltage operation, low power consumption, long-term reliability,
      and only an electronic switching mechanism, without an ionic-motion-related
      mechanism. 

PMID- 25973914
TI  - Survival and persistence of Bacillus clausii in the human gastrointestinal tract
      following oral administration as spore-based probiotic formulation.
AB  - AIMS: This study aimed to investigate the fate of Bacillus clausii spores orally
      administered as lyophilized or liquid formulation to healthy volunteers. METHODS
      AND RESULTS: The study was a randomized, open-label, cross-over trial in which
      two commercial probiotic formulations containing spores of four antibiotic
      resistant B. clausii strains (OC, NR, SIN, T) were given as a single dose
      administration. Faecal B. clausii units of each strain were counted on selective
      media and extrapolated for the total weight of evacuated faeces. RAPD-PCR typing
      was used to confirm B. clausii identification. Bacillus clausii was found alive
      in faeces for up to 12 days. In some volunteers, the recovered amount of OC, NR
      or SIN was higher than the number of administered spores. Bioequivalence among
      the two formulations was demonstrated. CONCLUSIONS: Bacillus clausii spores
      survive transit through the human gastrointestinal tract. They can undergo
      germination, outgrowth and multiplication as vegetative forms. Bacillus clausii
      strains can have different ability to survive in the intestinal environment.
      Bacillus clausii spores administered as liquid suspension or lyophilized form
      behave similarly in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: This work
      contributes towards a better understanding of the behaviour of B. clausii spores
      as probiotics.

PMID- 25973916
TI  - Efficient Radioisotope Energy Transfer by Gold Nanoclusters for Molecular
      Imaging.
AB  - Beta-emitting isotopes Fluorine-18 and Yttrium-90 are tested for their potential
      to stimulate gold nanoclusters conjugated with blood serum proteins (AuNCs).
      AuNCs excited by either medical radioisotope are found to be highly effective
      ionizing radiation energy transfer mediators, suitable for in vivo optical
      imaging. AuNCs synthesized with protein templates convert beta-decaying
      radioisotope energy into tissue-penetrating optical signals between 620 and 800
      nm. Optical signals are not detected from AuNCs incubated with Technetium-99m, a
      pure gamma emitter that is used as a control. Optical emission from AuNCs is not
      proportional to Cerenkov radiation, indicating that the energy transfer between
      the radionuclide and AuNC is only partially mediated by Cerenkov photons. A
      direct Coulombic interaction is proposed as a novel and significant mechanism of
      energy transfer between decaying radionuclides and AuNCs. 

PMID- 25973915
TI  - Inhibition of STAT3, FAK and Src mediated signaling reduces cancer stem cell
      load, tumorigenic potential and metastasis in breast cancer.
AB  - Cancer stem cells (CSCs) are responsible for aggressive tumor growth, metastasis
      and therapy resistance. In this study, we evaluated the effects of Shikonin (Shk)
      on breast cancer and found its anti-CSC potential. Shk treatment decreased the
      expression of various epithelial to mesenchymal transition (EMT) and CSC
      associated markers. Kinase profiling array and western blot analysis indicated
      that Shk inhibits STAT3, FAK and Src activation. Inhibition of these signaling
      proteins using standard inhibitors revealed that STAT3 inhibition affected CSCs
      properties more significantly than FAK or Src inhibition. We observed a
      significant decrease in cell migration upon FAK and Src inhibition and decrease
      in invasion upon inhibition of STAT3, FAK and Src. Combined inhibition of STAT3
      with Src or FAK reduced the mammosphere formation, migration and invasion more
      significantly than the individual inhibitions. These observations indicated that
      the anti-breast cancer properties of Shk are due to its potential to inhibit
      multiple signaling proteins. Shk also reduced the activation and expression of
      STAT3, FAK and Src in vivo and reduced tumorigenicity, growth and metastasis of
      4T1 cells. Collectively, this study underscores the translational relevance of
      using a single inhibitor (Shk) for compromising multiple tumor-associated
      signaling pathways to check cancer metastasis and stem cell load. 

PMID- 25973917
TI  - Selection of genes associated with variations in the Circle of Willis in gerbils
      using suppression subtractive hybridization.
AB  - Deformities in the Circle of Willis (CoW) can significantly increase the risk of
      cerebrovascular disease in humans. However, the molecular mechanisms underlying
      these deformities have not been understood. Based on our previous studies,
      variations in the CoW of gerbils are hereditary. A normal CoW is observed in
      approximately 60% of gerbils, a percentage that also applies to humans. Thus,
      gerbil is an ideal experimental model for studying variations in the CoW. To
      study the mechanisms underlying these variations, we selected genes associated
      with different types of the CoW using suppression subtractive hybridization
      (SSH). After evaluating the efficiency of SSH using quantitative real-time
      polymerase chain reaction (qPCR) on subtracted and unsubtracted cDNA and Southern
      blotting on SSH PCR products, 12 SSH libraries were established. We identified 4
      genes (CST3, GNAS, GPx4 and PFN2) associated with variations in the CoW. These
      genes were identified with qPCR and Western blotting using 70 expressed sequence
      tags from the SSH libraries. Cloning and sequencing allowed us to demonstrate
      that the 4 genes were closely related to mouse genes. We may assume that these 4
      genes play an important role in the development of variations in the CoW. This
      study provides a foundation for further research of genes related to development
      of variations in the CoW and the mechanisms of dysmorphosis of cerebral vessels. 

PMID- 25973919
TI  - Predicting recovery of voluntary upper extremity movement in subacute stroke
      patients with severe upper extremity paresis.
AB  - BACKGROUND AND OBJECTIVE: Prediction of voluntary upper extremity (UE) movement
      recovery is largely unknown in patients with little voluntary UE movement at
      admission. The present study aimed to investigate (1) the extent and variation of
      voluntary UE movement recovery, and (2) the best predictive model of the recovery
      of voluntary UE movement by clinical variables in patients with severe UE
      paresis. DESIGN: Prospective cohort study. METHODS: 140 (out of 590) stroke
      patients with severe UE paresis completed all assessments. Voluntary UE movement
      was assessed using the UE subscale of the Stroke Rehabilitation Assessment of
      Movement (STREAM-UE). Two outcome measures, STREAM-UE scores at discharge
      (DC(STREAM-UE)) and changes between admission and discharge (Delta(STREAM-UE)),
      were investigated to represent the final states and improvement of the recovery
      of voluntary UE movement. Stepwise regression analyses were used to investigate
      19 clinical variables and to find the best predictive models of the two outcome
      measures. RESULTS: The participants showed wide variation in both DC(STREAM-UE)
      and Delta(STREAM-UE). 3.6% of the participants almost fully recovered at
      discharge (DC(STREAM-UE) > 15). A large improvement (Delta(STREAM-UE) >= 10)
      occurred in 16.4% of the participants, while 32.9% of the participants did not
      have any improvement. The four predictors for the DC(STREAM-UE) (R(2) = 35.0%)
      were 'baseline STREAM-UE score', 'hemorrhagic stroke', 'baseline National
      Institutes of Health Stroke Scale (NIHSS) score', and 'cortical lesion excluding
      primary motor cortex'. The three predictors for the Delta(STREAM-UE) (R(2) =
      22.0%) were 'hemorrhagic stroke', 'baseline NIHSS score', and 'cortical lesion
      excluding primary motor cortex'. CONCLUSIONS: Recovery of voluntary UE movement
      varied widely in patients with severe UE paresis after stroke. The predictive
      power of clinical variables was poor. Both results indicate the complex nature of
      voluntary UE movement recovery in patients with severe UE paresis after stroke.

PMID- 25973920
TI  - Systems biology for biologists.

PMID- 25973918
TI  - Comparative Transcriptomics of Sijung and Jumli Marshi Rice during Early Chilling
      Stress Imply Multiple Protective Mechanisms.
AB  - INTRODUCTION: Low temperature is one of the major environmental factors that
      adversely affect plant growth and yield. Many cereal crops from tropical regions,
      such as rice, are chilling sensitive and, therefore, are affected already at <10 
      degrees C. Interestingly, it has been demonstrated that chilling susceptibility
      varies greatly among rice varieties, which indicates differences in the
      underlying molecular responses. Understanding these differences is vital for
      continued development of rational breeding and transgenic strategies for more
      tolerant varieties. Thus, in this study, we conducted a comparative global gene
      expression profiling analysis of the chilling tolerant varieties Sijung and Jumli
      Marshi (spp. Japonica) during early chilling stress (<24 h, 10  degrees C).
      METHODS AND RESULTS: Global gene expression experiments were conducted with
      Agilent Rice Gene Expression Microarray 4 x 44 K. The analysed results showed
      that there was a relatively low (percentage or number) overlap in differentially
      expressed genes in the two varieties and that substantially more genes were up
      regulated in Jumli Marshi than in Sijung but the number of down-regulated genes
      were higher in Sijung. In broad GO annotation terms, the activated response
      pathways in Sijung and Jumli Marshi were coherent, as a majority of the genes
      belonged to the catalytic, transcription regulator or transporter activity
      categories. However, a more detailed analysis revealed essential differences. For
      example, in Sijung, activation of calcium and phosphorylation signaling pathways,
      as well as of lipid transporters and exocytosis-related proteins take place very
      early in the stress response. Such responses can be coupled to processes aimed at
      strengthening the cell wall and plasma membrane against disruption. On the
      contrary, in Jumli Marshi, sugar production, detoxification, ROS scavenging,
      protection of chloroplast translation, and plausibly the activation of the
      jasmonic acid pathway were the very first response activities. These can instead
      be coupled to detoxification processes. CONCLUSIONS: Based on the results
      inferred from this study, we conclude that different, but overlapping, strategies
      are undertaken by the two varieties to cope with the chilling stress; in Sijung
      the initial molecular responses seem to be mainly targeted at strengthening the
      cell wall and plasma membrane, whereas in Jumli Marshi the protection of
      chloroplast translation and detoxification is prioritized.

PMID- 25973921
TI  - Determination of Multimodal Isotopic Distributions: The Case of a (15)N Labeled
      Protein Produced into Hairy Roots.
AB  - Isotopic labeling is widely used in various fields like proteomics, metabolomics,
      fluxomics, as well as in NMR structural studies, but it requires an efficient
      determination of the isotopic enrichment. Mass spectrometry is the method of
      choice for such analysis. However, when complex expression systems like hairy
      roots are used for production, multiple populations of labeled proteins may be
      obtained. If the isotopic incorporation determination is actually well-known for
      unimodal distributions, the multimodal distributions have scarcely been
      investigated. Actually, only a few approaches allow the determination of the
      different labeled population proportions from multimodal distributions.
      Furthermore, they cannot be used when the number of the populations and their
      respective isotope ratios are unknown. The present study implements a new
      strategy to measure the (15)N labeled populations inside a multimodal
      distribution knowing only the peptide sequence and peak intensities from mass
      spectrometry analyses. Noteworthy, it could be applied to other elements, like
      carbon and hydrogen, and extended to a larger range of biomolecules. 

PMID- 25973922
TI  - A panel of novel biomarkers representing different disease pathways improves
      prediction of renal function decline in type 2 diabetes.
AB  - OBJECTIVE: We aimed to identify a novel panel of biomarkers predicting renal
      function decline in type 2 diabetes, using biomarkers representing different
      disease pathways speculated to contribute to the progression of diabetic
      nephropathy. RESEARCH DESIGN AND METHODS: A systematic data integration approach
      was used to select biomarkers representing different disease pathways. Twenty
      eight biomarkers were measured in 82 patients seen at an outpatient diabetes
      center in The Netherlands. Median follow-up was 4.0 years. We compared the cross
      validated explained variation (R2) of two models to predict eGFR decline, one
      including only established risk markers, the other adding a novel panel of
      biomarkers. Least absolute shrinkage and selection operator (LASSO) was used for
      model estimation. The C-index was calculated to assess improvement in prediction
      of accelerated eGFR decline defined as <-3.0 mL/min/1.73m2/year. RESULTS:
      Patients' average age was 63.5 years and baseline eGFR was 77.9 mL/min/1.73m2.
      The average rate of eGFR decline was -2.0 +/- 4.7 mL/min/1.73m2/year. When
      modeled on top of established risk markers, the biomarker panel including matrix
      metallopeptidases, tyrosine kinase, podocin, CTGF, TNF-receptor-1, sclerostin,
      CCL2, YKL-40, and NT-proCNP improved the explained variability of eGFR decline
      (R2 increase from 37.7% to 54.6%; p=0.018) and improved prediction of accelerated
      eGFR decline (C-index increase from 0.835 to 0.896; p=0.008). CONCLUSIONS: A
      novel panel of biomarkers representing different pathways of renal disease
      progression including inflammation, fibrosis, angiogenesis, and endothelial
      function improved prediction of eGFR decline on top of established risk markers
      in type 2 diabetes. These results need to be confirmed in a large prospective
      cohort.

PMID- 25973923
TI  - Slow breathing and hypoxic challenge: cardiorespiratory consequences and their
      central neural substrates.
AB  - Controlled slow breathing (at 6/min, a rate frequently adopted during yoga
      practice) can benefit cardiovascular function, including responses to hypoxia. We
      tested the neural substrates of cardiorespiratory control in humans during
      volitional controlled breathing and hypoxic challenge using functional magnetic
      resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced
      (slow and normal rate) breathing and during spontaneous breathing of normoxic and
      hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were
      acquired concurrently, including beat-to-beat blood pressure from a subset of
      participants (N = 7). Slow breathing was associated with increased tidal
      ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate
      variability. Within the brain, slow breathing activated dorsal pons,
      periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and
      anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral
      amygdalae, anterior insular and occipitotemporal cortices. Interaction between
      slow breathing and hypoxia was expressed in ventral striatal and frontal polar
      activity. Across conditions, within brainstem, dorsal medullary and pontine
      activity correlated with tidal volume and inversely with heart rate. Activity in
      rostroventral medulla correlated with beat-to-beat blood pressure and heart rate
      variability. Widespread insula and striatal activity tracked decreases in heart
      rate, while subregions of insular cortex correlated with momentary increases in
      tidal volume. Our findings define slow breathing effects on central and
      cardiovascular responses to hypoxic challenge. They highlight the recruitment of
      discrete brainstem nuclei to cardiorespiratory control, and the engagement of
      corticostriatal circuitry in support of physiological responses that accompany
      breathing regulation during hypoxic challenge. 

PMID- 25973924
TI  - Association of respiratory viruses with outcomes of severe childhood pneumonia in
      Botswana.
AB  - BACKGROUND: The highest incidence of childhood acute lower respiratory tract
      infection (ALRI) is in low- and middle-income countries. Few studies examined
      whether detection of respiratory viruses predicts ALRI outcomes in these
      settings. METHODS: We conducted prospective cohort and case-control studies of
      children 1-23 months of age in Botswana. Cases met clinical criteria for
      pneumonia and were recruited within six hours of presentation to a referral
      hospital. Controls were children without pneumonia matched to cases by primary
      care clinic and date of enrollment. Nasopharyngeal specimens were tested for
      respiratory viruses using polymerase chain reaction. We compared detection rates
      of specific viruses in matched case-control pairs. We examined the effect of
      respiratory syncytial virus (RSV) and other respiratory viruses on pneumonia
      outcomes. RESULTS: Between April 2012 and August 2014, we enrolled 310 cases, of
      which 133 had matched controls. Median ages of cases and controls were 6.1 and
      6.4 months, respectively. One or more viruses were detected from 75% of cases and
      34% of controls. RSV and human metapneumovirus were more frequent among cases
      than controls, but only enterovirus/rhinovirus was detected from asymptomatic
      controls. Compared with non-RSV viruses, RSV was associated with an increased
      risk of treatment failure at 48 hours [risk ratio (RR): 1.85; 95% confidence
      interval (CI): 1.20, 2.84], more days of respiratory support [mean difference
      (MD): 1.26 days; 95% CI: 0.30, 2.22 days], and longer duration of hospitalization
      [MD: 1.35 days; 95% CI: 0.20, 2.50 days], but lower in-hospital mortality [RR:
      0.09; 95% CI: 0.01, 0.80] in children with pneumonia. CONCLUSIONS: Respiratory
      viruses were detected from most children hospitalized with ALRI in Botswana, but
      only RSV and human metapneumovirus were more frequent than among children without
      ALRI. Detection of RSV from children with ALRI predicted a protracted illness
      course but lower mortality compared with non-RSV viruses.

PMID- 25973926
TI  - Migration of Transformed Bone Marrow-Derived Cells with Peripheral Neural Tumor
      Traits In Vivo.
AB  - The identification of the original cells in tumors may allow for measures that
      protect the original cells and prevent tumor formation. In the present study, we
      isolated a subpopulation of cells with the features of neural tumor cells from
      transformed BMDCs in vitro. These neural tumor cells expressed the markers of
      neural tumor progenitor cells and differentiated neural tumor cells in vitro.
      Moreover, the subcloned cells from transformed BMDCs could migrate to distant
      tissues and drive peripheral neural tumors in vivo. Therefore, our results
      further verify that transformed mouse BMDCs are a potential source of peripheral
      neural tumors. 

PMID- 25973925
TI  - Neuropsychological Impairment in Prodromal, First-Episode, and Chronic Psychosis:
      Assessing RBANS Performance.
AB  - BACKGROUND: Cognitive deficits are observed throughout all developmental phases
      of psychosis. However, prior studies have usually focused on a limited illness
      period and used a wide variety of cognitive instruments. Therefore, it has been
      difficult to characterize or highlight cognitive functioning in different stages
      of psychosis. METHOD: We administered the RBANS (Repeatable Battery for the
      Assessment of Neuropsychological Status) tests to 4 participant subgroups,
      including healthy volunteers (controls, HC, n = 28), subjects at high risk for
      clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients
      (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch
      Sz, n =147). Comparison, correlation, and regression analyses of RBANS index
      scores were assessed among groups. We examined clinical outcomes over 2 years
      between the CHR and HC subjects, and RBANS domains were used as possible
      predictors for conversion to psychosis. RESULTS: Performance on all RBANS domains
      was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch
      Sz), and RBANS scores declined along with disease progression. Regression
      analyses showed that for CHR and HC subjects, baseline impairment in delayed
      memory (DM) significantly predicted conversion to psychosis. Additionally,
      partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only
      correlate with a later stage of psychosis. CONCLUSIONS: Cognitive deficits
      broadly emerged, and diminished functioning followed along with disease
      progression. Impairment in DM is perhaps one domain that helps us understand the
      development of psychosis. A critical need is to monitor and treat memory
      functioning for psychotic patients throughout all phases of the disease.

PMID- 25973927
TI  - Sociodemographic conditions, knowledge of dental diseases, dental care, and
      dietary habits.
AB  - OBJECTIVES: This study's aim was to present data on the sociodemographic
      conditions, knowledge of dental diseases, dental care, and dietary habits among
      children aged 3, 5, 10, and 15 years in Da Nang, Vietnam. METHODS: A cross
      sectional epidemiological questionnaire study was conducted in a population of
      840 children randomly selected by their year and month of birth (January to
      July), including 210 individuals in each age group. A self-reported questionnaire
      was completed by the parents of 3- and 5-year-olds, and a modified questionnaire
      was given to 10- and 15-year-olds to complete by themselves. RESULTS: Mass media
      constituted the main source of oral healthcare information. Parents assisted with
      tooth brushing in 86 percent of 3-year-olds and 71 percent of 5-year-olds.
      Fluoride toothpaste was used by 44-78 percent of children, with no clear age
      related trend. Within the past year, 60 percent of 3- and 5-year-olds, 20 percent
      of 10-year-olds, and 49 percent of 15-year-olds reported they had not visited a
      dental professional. Sweets were consumed between principal meals by 70-80
      percent of children. Milk with sugar was regularly consumed by 71 percent of 3
      year-olds and 91 percent of 5-year-olds. CONCLUSIONS: Children showed frequent
      sugar consumption and insufficient frequency of brushing their teeth with
      fluoride toothpaste. Food-based dietary guidelines should play a significant role
      in nutrition and oral health. It is especially important that oral health
      prevention programs reach preschool children before they establish unhealthy
      dietary habits. Parental education about oral health and access to oral
      healthcare services are also needed to improve children's oral health.

PMID- 25973928
TI  - Application of Physiologically Based Absorption Modeling for Amphetamine Salts
      Drug Products in Generic Drug Evaluation.
AB  - Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used
      for the treatment of attention deficit hyperactivity disorder. We developed
      physiologically based absorption models for mixed AMP salts ER capsules and
      dextroamphetamine sulfate ER capsules to address specific questions raised during
      generic drug postmarketing surveillance and bioequivalence (BE) guidance
      development. The models were verified against several data sets. Virtual BE
      simulations were conducted to assess BE in various populations other than normal
      healthy subjects where BE studies are generally conducted for approval. The
      models were also used to predict pharmacokinetics (PK) for hypothetical
      formulations having dissolution profiles falling within specification after the
      development of in vitro-in vivo relation. Finally, we demonstrated how to use the
      models to test sensitivity of PK metrics to the changes in formulation variables.

PMID- 25973930
TI  - Vascular biology 2014 in Monterey, California: celebrating 20 years of NAVBO.
AB  - A meeting report for Vascular Biology 2014, held in Monterey, California and
      organized by the North American Vascular Biology Organization (NAVBO). 

PMID- 25973929
TI  - Optogenetic stimulation of mPFC pyramidal neurons as a conditioned stimulus
      supports associative learning in rats.
AB  - It is generally accepted that the associative learning occurs when a behaviorally
      neutral conditioned stimulus (CS) is paired with an aversive unconditioned
      stimulus (US) in close temporal proximity. Eyeblink conditioning (EBC) is a
      simple form of associative learning for motor responses. Specific activation of a
      population of cells may be an effective and sufficient CS for establishing EBC.
      However, there has been no direct evidence to support this hypothesis. Here, we
      show in rats that optogenetic activation of the right caudal mPFC pyramidal
      neurons as a CS is sufficient to support the acquisition of delay eyeblink
      conditioning (DEC). Interestingly, the associative memory was not stably
      expressed during the initial period of daily conditioning session even after the
      CR acquisition reached the asymptotic level. Finally, the intensity and
      consistency of the CS were found to be crucial factors in regulating the
      retrieval of the associative memory. These results may be of importance in
      understanding the neural cellular mechanisms underlying associative learning and
      the mechanisms underlying retrieval process of memory. 

PMID- 25973931
TI  - Use of transcutaneous electrical nerve stimulation for chronic pruritus.
AB  - Pruritus is a distressing symptom in many dermatological as well as systemic
      conditions, and it is sometimes very chronic and relapsing. Transcutaneous
      electrical nerve stimulation (TENS) is an inexpensive form of analgesia that
      could also ameliorate itching. This study aimed to evaluate TENS efficacy in
      patients with pruritus due to some types of chronic eczema, and in patients with
      chronic hepatic disease. Ten patients with atopic dermatitis (AD), 20 patients
      with lichen simplex chronicus (LSC), and 16 patients with chronic liver disease
      having chronic distressing pruritus received three sessions of TENS weekly for 12
      sessions, and the effect on the visual analogue scale (VAS) scores was recorded
      after 2 weeks of therapy, at treatment end, and after an additional month for
      follow up. There was a statistically significant decline in the mean VAS score
      for studied groups at weeks 2 and 4 of therapy compared to baseline, but the
      improvement was more significant in patients with AD, and LSC (p < 0.001 for
      both) than in those with chronic liver disease (p < 0.01) who also showed an
      early re-elevation of VAS score on follow up. TENS therapy holds promise as a
      palliative, alternative, safe and inexpensive treatment for patients with some
      chronic pruritic conditions. 

PMID- 25973933
TI  - Comparative epidemiology of Streptococcus pyogenes emm-types causing invasive and
      noninvasive infections in French children by use of high-resolution melting
      polymerase chain reaction.
AB  - BACKGROUND: This study aims to analyze the epidemiology of Group A streptococci
      (GAS) emm-types causing invasive and noninvasive infections in French children.
      METHODS: From September 2009 to May 2011, we analyzed GAS isolates from 585
      pharyngitis, 125 invasive infections and, for the first time in France, 32
      healthy carriers. M protein gene (emm) typing of the isolates was carried out by
      a new rapid technique, combining 3 multiplex-polymerase chain reactions (PCRs)
      coupled to high-resolution melting (HRM) curves, able to detect 13 major emm
      types (emm 1, 3, 4, 6, 11, 12, 22, 28, 75, 77, 87, 89 and 102). RESULTS: GAS
      belonging to emm-type 1 were more frequently found among invasive infections than
      among pharyngitis (24.0% vs. 11.5%, P < 0.001); emm 4 and 89 were more common in
      pharyngitis than in invasive infections (emm-type 4, 17.4% vs. 6.4%, P = 0.002
      and emm-type 89, 9.9% vs. 2.4%, P = 0.006, respectively) and emm 3 and 4 were
      more common in cases of pharyngitis associated with scarlet fever (21.6% vs.
      6.0%, P < 0.001 and 29.3% vs. 14.5%, P < 0.001, respectively). CONCLUSION: HRM
      method enables the rapid emm-typing of a large number of isolates in
      epidemiological studies. Comparison of GAS causing invasive and noninvasive
      infections in the same population of children displays an unbalanced repartition
      of emm-types.

PMID- 25973932
TI  - The 4E-BP Caf20p Mediates Both eIF4E-Dependent and Independent Repression of
      Translation.
AB  - Translation initiation factor eIF4E mediates mRNA selection for protein synthesis
      via the mRNA 5'cap. A family of binding proteins, termed the 4E-BPs, interact
      with eIF4E to hinder ribosome recruitment. Mechanisms underlying mRNA specificity
      for 4E-BP control remain poorly understood. Saccharomyces cerevisiae 4E-BPs,
      Caf20p and Eap1p, each regulate an overlapping set of mRNAs. We undertook global
      approaches to identify protein and RNA partners of both 4E-BPs by
      immunoprecipitation of tagged proteins combined with mass spectrometry or next
      generation sequencing. Unexpectedly, mass spectrometry indicated that the 4E-BPs
      associate with many ribosomal proteins. 80S ribosome and polysome association was
      independently confirmed and was not dependent upon interaction with eIF4E, as
      mutated forms of both Caf20p and Eap1p with disrupted eIF4E-binding motifs retain
      ribosome interaction. Whole-cell proteomics revealed Caf20p mutations cause both
      up and down-regulation of proteins and that many changes were independent of the
      4E-binding motif. Investigations into Caf20p mRNA targets by immunoprecipitation
      followed by RNA sequencing revealed a strong association between Caf20p and mRNAs
      involved in transcription and cell cycle processes, consistent with observed cell
      cycle phenotypes of mutant strains. A core set of over 500 Caf20p-interacting
      mRNAs comprised of both eIF4E-dependent (75%) and eIF4E-independent targets
      (25%), which differ in sequence attributes. eIF4E-independent mRNAs share a 3'
      UTR motif. Caf20p binds all tested motif-containing 3' UTRs. Caf20p and the 3'UTR
      combine to influence ERS1 mRNA polysome association consistent with Caf20p
      contributing to translational control. Finally ERS1 3'UTR confers Caf20-dependent
      repression of expression to a heterologous reporter gene. Taken together, these
      data reveal conserved features of eIF4E-dependent Caf20p mRNA targets and uncover
      a novel eIF4E-independent mode of Caf20p binding to mRNAs that extends the
      regulatory role of Caf20p in the mRNA-specific repression of protein synthesis
      beyond its interaction with eIF4E. 

PMID- 25973934
TI  - Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian
      neonates less than 2500 g.
AB  - BACKGROUND: Lactoferrin (LF) is a broad-spectrum antimicrobial and
      immunomodulatory milk glycoprotein. OBJECTIVE: To determine the effect of bovine
      LF on the prevention of the first episode of late-onset sepsis in Peruvian
      infants. METHODS: We conducted a pilot randomized placebo-controlled double blind
      study in infants with a birth weight (BW) less than 2500g in 3 Neonatal Units in
      Lima. Patients were randomized to receive bovine LF 200mg/kg/d or placebo for 4
      weeks. RESULTS: One hundred and ninety neonates with a BW of 1591 +/- 408 g and a
      gestational age of 32.1 +/- 2.6 weeks were enrolled. Overall, 33 clinically
      defined first late-onset sepsis events occurred. The cumulative sepsis incidence
      in the LF group was 12/95 (12.6%) versus 21/95 (22.1%) in the placebo group, and
      20% (8/40) versus 37.5% (15/40) for infants less than or equal to 1500 g. The
      hazard ratio of LF, after adjustment by BW, was 0.507 (95% CI: 0.249-1.034).
      There were 4 episodes of culture-proven sepsis in the LF group versus 4 in the
      placebo group. Considering that children did not received the intervention until
      the start of oral or tube feeding, we ran a secondary exploratory analysis using
      time since the start of the treatment; in this model, LF achieved significance.
      There were no serious adverse events attributable to the intervention.
      CONCLUSIONS: Overall sepsis occurred less frequently in the LF group than in the
      control group. Although the primary outcome did not reach statistical
      significance, the confidence interval is suggestive of an effect that justifies a
      larger trial.

PMID- 25973935
TI  - Economic analysis of rapid and sensitive polymerase chain reaction testing in the
      emergency department for influenza infections in children.
AB  - BACKGROUND: Rapid multiplex polymerase chain reaction (PCR) assays simultaneously
      detect several respiratory viral pathogens with high sensitivity. Maximizing
      detection of influenza at the point of care has the potential to reduce
      unnecessary antibiotic use, laboratory tests and hospitalizations. However, the
      cost-effectiveness of rapid multiplex PCR assays for influenza has not been
      compared with other diagnostic methods in children. METHODS: For children
      presenting to the emergency department with influenza-like illness, we compared
      costs and outcomes using 4 different testing strategies for detection of
      influenza: (1) a rapid multiplex PCR platform (FilmArray); (2) traditional PCR;
      (3) direct-fluorescent antibody and (4) rapid antigen tests. Costs were assessed
      from the hospital perspective, and effectiveness was defined as quality-adjusted
      life years (QALYs). Input parameters were obtained from previous studies, and the
      model was run separately for children aged 3-36 months and 3-18 years. RESULTS:
      Rapid multiplex PCR testing was the most effective testing strategy for children
      in both age groups. The incremental cost-effectiveness when compared with rapid
      antigen tests was $115,556 per QALY for children aged 3-36 months and from
      $228,000 per QALY for children aged 3-18 years. The cost-effectiveness of rapid
      multiplex PCR was sensitive to estimates for influenza prevalence, the proportion
      of patients treated with antivirals and the cost per test. CONCLUSIONS: Our model
      identifies scenarios in which identification of influenza in the emergency
      department using rapid multiplex PCR testing is a cost-effective strategy for
      infants and children 3 months through 18 years. Including detection of other
      respiratory viruses in the analysis would further improve cost-effectiveness.

PMID- 25973936
TI  - Cost of measles containment in an ambulatory pediatric clinic.
AB  - BACKGROUND: Measles is highly infectious; prompt containment of illnesses is
      necessary to prevent spread. In August 2013, a 13-year-old male with measles
      exposed patients and employees in a pediatric clinic. We studied containment
      costs to identify avoidable costs. METHODS: Measles exposure was defined as in
      person contact with or presence in the same room <2 hours after the measles
      patient. Costs were calculated retrospectively using published costs of measles
      mumps-rubella vaccine, cost-to-charge ratios for inpatient care in urban
      Washington State and local emergency department charges for post-exposure
      immunoglobulin (IG). Personnel costs were calculated by multiplying hourly wages
      by time for employees who worked on the response; overhead was excluded. RESULTS:
      Fifty-two patients, 60 caretakers and 10 employees were exposed. Personnel time
      cost $1961. Exposed patients had a mean age of 9.6 years (range: 2 months-19
      years); 34 (65%) were fully vaccinated, and 18 (35%) were <12 months of age and
      too young to be vaccinated. Five patients (10%) were <6 months of age and
      required IG; 13 infants (25%) 6-11 months of age required measles-mumps-rubella
      vaccination. Caretakers followed up with their physicians for evidence of
      immunity. One employee had documented evidence of immunity; 9 required measles
      antibody testing or vaccination. Management of exposed persons cost $3694;
      overall clinic costs were $5655. CONCLUSION: Responding to 1 measles case cost
      the pediatric clinic more than $5000, despite isolating the patient promptly
      after examination. Documentation of employee immunity, vaccination of eligible
      patients and strict infection control precautions might reduce ambulatory costs
      associated with measles containment.

PMID- 25973937
TI  - Tuberculin skin testing and T-SPOT.TB in internationally adopted children.
AB  - BACKGROUND: Diagnosis of latent tuberculosis infection is a problem in children
      because of lack of a diagnostic standard and potential impact of previous Bacille
      Calmette-Guerin vaccination and exposure to environmental mycobacteria.
      Effectiveness and usefulness of interferon-gamma release assays in infants and
      younger children have yet to be clearly demonstrated. METHODS: Prospective cohort
      study including 109 children (4 months to 16 years) seen in an international
      adoption clinic at Nationwide Children's Hospital, Columbus, OH. Children were
      adopted from 14 countries, mostly (72.5%) from China, Russia and Ethiopia.
      Correspondence between tuberculin skin test (TST) and the T-SPOT.TB assay was
      evaluated. Factors associated with positive results on the TST and T-SPOT.TB were
      determined, and the impact of age on test performance was specifically addressed.
      RESULTS: TST was positive in 23.4% (25 of 107). T-SPOT.TB was positive in 4.6% (5
      of 109). Overall agreement between TST and T-SPOT.TB was 71%, with prevalence
      adjusted, bias-adjusted Kappa of 0.68. History of Mycobacterium tuberculosis
      exposure was associated with positive results on TST (odds ratio: 25.4, 95%
      confidence interval: 4.8-261.6, exact logistic regression) and T-SPOT.TB (odds
      ratio: 78.9, 95% confidence interval: 9.7-infinity). All 5 children with positive
      T-SPOT.TB had TST induration >=15 mm. No patient less than 1 year of age (n = 17)
      had positive TST or T-SPOT.TB. Positive TST was not associated with Bacille
      Calmette-Guerin vaccination or scar. CONCLUSIONS: TST was positive in a
      significant percentage of international adoptees. T-SPOT.TB was rarely positive
      and discordant results reflected negative T-SPOT.TB with positive TST. In this
      population latent tuberculosis infection may be over-estimated by TST.
      Regardless, in our context at the time of the study, treatment decisions were
      based upon TST results, not results of the T-SPOT.TB assay. Age was consistently
      associated with findings on TST and T-SPOT.TB with no positive result on either
      test for any child <1 year of age.

PMID- 25973938
TI  - Posaconazole: promising but problematic in practice in pediatric patients.
AB  - Posaconazole is a broad-spectrum antifungal agent used for the prevention and
      treatment of invasive fungal infections. It is currently only licensed for use in
      children greater than 12 years of age. Absorption of the oral formulation is
      unpredictable and affected by mucositis and concomitant medications. We reviewed
      studies of posaconazole use in children younger than 12 years in relation to
      attainment of target serum concentrations. 

PMID- 25973939
TI  - False-positive HIV test results in infancy and management of uninfected children
      receiving antiretroviral therapy.
AB  - This report summarizes 2 children misdiagnosed with HIV infection in a clinic in
      rural Zambia and discusses the implications of false-positive HIV DNA tests in
      HIV-exposed infants, including the potential magnitude of the problem.
      Recommendations are needed to address the management of children receiving
      antiretroviral therapy who are suspected of being uninfected. 

PMID- 25973940
TI  - Long-term trends in invasive Haemophilus influenzae type B disease among
      indigenous Australian children following use of PRP-OMP and PRP-T vaccines.
AB  - BACKGROUND: Among indigenous populations with high incidence and early onset of
      invasive Haemophilus influenzae type b (Hib) disease, PRP-OMP vaccines are used
      in the United States and PRP-T vaccines in Canada. In Australia, PRP-OMP vaccines
      were exclusively used in indigenous children from 1993 until they were replaced
      by PRP-T between late 2005 and 2009. METHODS: Analytic descriptive study of 20
      years of enhanced surveillance data (1993-2013) for invasive Hib disease in
      Australian children <10 years of age was conducted. RESULTS: Of 579 Hib cases
      under 10 years of age reported from vaccine introduction in 1993 to 2013, 78
      (13%) were in indigenous children, 47 (60%) of whom lived in regions with high
      prevaccine incidence. In this population, incidence per 100,000 declined from
      18.1 (95% confidence interval [CI]: 10.4, 29.4) in the early PRP-OMP period (1993
      1996) to 6.2 (95% CI: 4.0, 9.2) and 4.7 (95% CI: 1.7, 10.3) in the later PRP-OMP
      (1996-2009) and PRP-T periods (2009-2013), respectively. The
      indigenous:nonindigenous incidence rate ratio increased to 43 (95% CI: 16, 145)
      and 58 (95% CI: 7, 2660) in the later PRP-OMP and PRP-T periods, respectively,
      more than 10-fold higher than in lesser-incidence Australian regions.
      CONCLUSIONS: We found no change in Hib incidence among indigenous Australian
      children living in high-incidence regions in the first 4 years following a change
      to PRP-T-containing combination vaccines. This may be of relevance to North
      American indigenous populations characterized by suboptimal living conditions and
      young age of onset for whom PRP-OMP continues to be recommended, such as Alaska
      Natives.

PMID- 25973941
TI  - Pathogenic bacterial nasopharyngeal colonization and its impact on respiratory
      diseases in the first year of life: the PATCH Birth Cohort Study.
AB  - BACKGROUND: For acute respiratory diseases caused by bacteria, colonization in
      the respiratory tracts is often the first sign, although nasopharynx is the major
      source of secretions containing pathogens. To understand the pathogenesis of
      respiratory tract diseases, it is important to analyze the establishment of
      nasopharyngeal bacterial colonization. METHODS: Infants with nasopharyngeal swabs
      were examined at the age of 1, 2, 4, 6 and 12 months for the detection of
      pathogens, including Streptococcus pneumoniae, Hemophilus influenzae, Moraxella
      catarrhalis, Streptococcus pyogenes and Staphylococcus aureus. The methods used
      for detection were bacterial culture and multiplex polymerase chain reaction.
      RESULTS: From January 2012 to August 2013, a total of 320 neonates were enrolled,
      and 120 of them completed the first 12-month study. Staphylococcus aureus was the
      most common pathogen at all 5 time points while the rates declined; in contrast,
      the other 4 increased during the first year of life. Of our series, the multiplex
      polymerase chain reaction detection rates were higher than those of bacterial
      culture. More than 50% of Staphylococcus aureus was methicillin-resistant, and
      the trend decreased in the same period. In the analysis of factors associated
      with the development of infant wheeze, infants with maternal atopy [odds ratio
      (OR): 3.26; 95% confidence interval (CI): 1.20-8.88; P = 0.02] and pneumococcal
      colonization (OR: 15.64; 95% CI: 3.25-75.35; P = 0.001) had higher rates of
      wheeze. CONCLUSIONS: Bacterial interactions may result in differing pathogen
      prevalence in the first year of life. In addition, nasopharyngeal pneumococcal
      colonization may have an effect on the risk of infant wheeze. The result could
      help clinicians to clarify the relation between bacterial colonization and
      respiratory illnesses in infancy.

PMID- 25973942
TI  - Synthesis and immunological study of alpha-2,9-oligosialic acid conjugates as
      anti-group C meningitis vaccines.
AB  - alpha-2,9-Di-, tri-, tetra-, and pentasialic acids were prepared and conjugated
      with a carrier protein. The resultant glycoconjugates elicited robust T cell
      mediated immunity in mice. alpha-2,9-Trisialic acid was identified as a promising
      antigen for developing glycoconjugate vaccines against group C Neisseria
      meningitidis. 

PMID- 25973944
TI  - MicroRNA Detection: Current Technology and Research Strategies.
AB  - The relatively new field of microRNA (miR) has experienced rapid growth in
      methodology associated with its detection and bioanalysis as well as with its
      role in -omics research, clinical diagnostics, and new therapeutic strategies.
      The breadth of this area of research and the seemingly exponential increase in
      number of publications on the subject can present scientists new to the field
      with a daunting amount of information to evaluate. This review aims to provide a
      collective overview of miR detection methods by relating conventional,
      established techniques [such as quantitative reverse transcription polymerase
      chain reaction (RT-qPCR), microarray, and Northern blotting (NB)] and relatively
      recent advancements [such as next-generation sequencing (NGS), highly sensitive
      biosensors, and computational prediction of microRNA/targets] to common miR
      research strategies. This should guide interested readers toward a more focused
      study of miR research and the surrounding technology. 

PMID- 25973943
TI  - Genetic determinants for gestational diabetes mellitus and related metabolic
      traits in Mexican women.
AB  - Epidemiological and physiological similarities among Gestational Diabetes
      Mellitus (GDM) and Type 2 Diabetes (T2D) suggest that both diseases, share a
      common genetic background. T2D risk variants have been associated to GDM
      susceptibility. However, the genetic architecture of GDM is not yet completely
      understood. We analyzed 176 SNPs for 115 loci previously associated to T2D, GDM
      and body mass index (BMI), as well as a set of 118 Ancestry Informative Markers
      (AIMs), in 750 pregnant Mexican women. Association with GDM was found for two of
      the most frequently replicated T2D loci: a TCF7L2 haplotype (CTTC: rs7901695,
      rs4506565, rs7903146, rs12243326; P=2.16 x 10(-06); OR=2.95) and a KCNQ1
      haplotype (TTT: rs2237892, rs163184, rs2237897; P=1.98 x 10(-05); OR=0.55). In
      addition, we found two loci associated to glycemic traits: CENTD2 (60' OGTT
      glycemia: rs1552224, P=0.03727) and MTNR1B (HOMA B: rs1387153, P=0.05358).
      Remarkably, a major susceptibility SLC16A11 locus for T2D in Mexicans was not
      shown to play a role in GDM risk. The fact that two of the main T2D associated
      loci also contribute to the risk of developing GDM in Mexicans, confirm that both
      diseases share a common genetic background. However, lack of association with a
      Native American contribution T2D risk haplotype, SLC16A11, suggests that other
      genetic mechanisms may be in play for GDM.

PMID- 25973945
TI  - Perinatal factors associated with active intensive treatment at the border of
      viability: a population-based study.
AB  - OBJECTIVE: The aim of this national population-based study was to identify
      perinatal and neonatal factors associated with active intensive treatment (AIT)
      of infants born at the periviable period of 22 to 24 weeks of gestation. STUDY
      DESIGN: Data from the Israel national very low-birth weight infant database on
      2207 infants born alive in 1995 to 2010 at gestational age (GA) 22 to 24 weeks
      were evaluated. AIT was defined as endotracheal intubation in the delivery room
      or mechanical ventilation in the neonatal intensive care unit. Multivariable
      logistic regression analyses were used to identify the independent effect of
      demographic and perinatal factors on AIT for each gestational week. RESULT: Of
      the 2207 infants born at 22 to 24 weeks GA, 1643 (74.4%) received AIT and 564
      (25.6%) received comfort care. AIT increased from 25.5% at 22 weeks to 62.7 and
      93.5% at 23 and 24 weeks GA, respectively, reflecting a 4.66 (95% confidence
      interval (CI) 3.32 to 6.54)- and 29.8 (95% CI 19.9 to 44.6)-fold odds for AIT at
      23 and 24 weeks GA, respectively, compared with 22-week GA infants. Perinatal
      treatments associated with AIT included maternal tocolytic therapy (odds ratio
      (OR) 1.51, 95% CI 1.04 to 2.20), prenatal steroid therapy, both partial (OR 3.30,
      95% CI 2.14 to 5.10) and complete (OR 3.17, 95% CI 1.91 to 5.26) and cesarean
      delivery (OR 2.68, 95% CI 1.88 to 3.83). Each unit increase in birth weight z
      score was associated with an OR of 1.58 (95% CI 1.30 to 1.92) for AIT. At 22
      weeks GA, maternal tocolytic treatment was associated with higher odds of AIT. In
      the 23 and 24-week GA infants, maternal infertility treatment, antenatal
      steroids, cesarean delivery and higher-birth weight z-scores were significantly
      associated with AIT. Among 23-week GA infants, AIT decreased significantly in the
      period 2006 to 2010 compared with 1995 to 2000 (OR 0.51, 95% CI 0.34 to 0.77).
      CONCLUSION: An active approach in obstetric management of pregnancies appears to
      impact the neonatologists' decision to undertake AIT treatment in infants born at
      the border of viability. The higher odds for AIT associated with obstetric
      interventions might contribute to the reported beneficial effect of antenatal
      steroids and cesarean delivery on the survival of infants born at the border of
      viability.

PMID- 25973946
TI  - Revisiting GMOs: Are There Differences in European Consumers' Acceptance and
      Valuation for Cisgenically vs Transgenically Bred Rice?
AB  - Both cisgenesis and transgenesis are plant breeding techniques that can be used
      to introduce new genes into plant genomes. However, transgenesis uses gene(s)
      from a non-plant organism or from a donor plant that is sexually incompatible
      with the recipient plant while cisgenesis involves the introduction of gene(s)
      from a crossable--sexually compatible--plant. Traditional breeding techniques
      could possibly achieve the same results as those from cisgenesis, but would
      require a much larger timeframe. Cisgenesis allows plant breeders to enhance an
      existing cultivar more quickly and with little to no genetic drag. The current
      regulation in the European Union (EU) on genetically modified organisms (GMOs)
      treats cisgenic plants the same as transgenic plants and both are mandatorily
      labeled as GMOs. This study estimates European consumers' willingness-to-pay
      (WTP) for rice labeled as GM, cisgenic, with environmental benefits (which
      cisgenesis could provide), or any combination of these three attributes. Data
      were collected from 3,002 participants through an online survey administered in
      Belgium, France, the Netherlands, Spain and the United Kingdom in 2013. Censored
      regression models were used to model consumers' WTP in each country. Model
      estimates highlight significant differences in WTP across countries. In all five
      countries, consumers are willing-to-pay a premium to avoid purchasing rice
      labeled as GM. In all countries except Spain, consumers have a significantly
      higher WTP to avoid consuming rice labeled as GM compared to rice labeled as
      cisgenic, suggesting that inserting genes from the plant's own gene pool is more
      acceptable to consumers. Additionally, French consumers are willing-to-pay a
      premium for rice labeled as having environmental benefits compared to
      conventional rice. These findings suggest that not all GMOs are the same in
      consumers' eyes and thus, from a consumer preference perspective, the differences
      between transgenic and cisgenic products are recommended to be reflected in GMO
      labeling and trade policies.

PMID- 25973947
TI  - Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines
      2015.
AB  - BACKGROUND: Japanese (JPN) guidelines for the management of acute pancreatitis
      were published in 2006. The severity assessment criteria for acute pancreatitis
      were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW)
      in 2008, leading to their publication as the JPN Guidelines 2010. Following the
      2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the
      classifications of regional complications of pancreatitis were revised, the
      development of a minimally invasive method for local complications of
      pancreatitis spread, and emerging evidence was gathered and revised into the JPN
      Guidelines. METHODS: A comprehensive evaluation was carried out on the evidence
      for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on
      the concepts of the GRADE system (Grading of Recommendations Assessment,
      Development and Evaluation). With the graded recommendations, where the evidence
      was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional
      new meta-analysis, the results of which were included in the guidelines. RESULTS:
      Thirty-nine questions were prepared in 17 subject areas, for which 43
      recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic
      imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy,
      Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor,
      Nutritional support, Intensive care, management of Biliary Pancreatitis,
      management of Abdominal Compartment Syndrome, Interventions for the local
      complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis
      Bundles 2015). Meta-analysis was conducted in the following four subject areas
      based on randomized controlled trials: (1) prophylactic antibiotics use; (2)
      prophylactic pancreatic stent placement for the prevention of post-ERCP
      pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for
      the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the
      results of the meta-analysis, recommendations were graded to create useful
      information. In addition, a mobile application was developed, which made it
      possible to diagnose, assess severity and check pancreatitis bundles.
      CONCLUSIONS: The JPN Guidelines 2015 were prepared using the most up-to-date
      methods, and including the latest recommended medical treatments, and we are
      confident that this will make them easy for many clinicians to use, and will
      provide a useful tool in the decision-making process for the treatment of
      patients, and optimal medical support. The free mobile application and calculator
      for the JPN Guidelines 2015 is available via
      http://www.jshbps.jp/en/guideline/jpn-guideline2015.html.

PMID- 25973948
TI  - On the superposition principle in interference experiments.
AB  - The superposition principle is usually incorrectly applied in interference
      experiments. This has recently been investigated through numerics based on Finite
      Difference Time Domain (FDTD) methods as well as the Feynman path integral
      formalism. In the current work, we have derived an analytic formula for the
      Sorkin parameter which can be used to determine the deviation from the
      application of the principle. We have found excellent agreement between the
      analytic distribution and those that have been earlier estimated by numerical
      integration as well as resource intensive FDTD simulations. The analytic handle
      would be useful for comparing theory with future experiments. It is applicable
      both to physics based on classical wave equations as well as the non-relativistic
      Schrodinger equation. 

PMID- 25973950
TI  - The Downregulation of MiR-182 Is Associated with the Growth and Invasion of
      Osteosarcoma Cells through the Regulation of TIAM1 Expression.
AB  - BACKGROUND: Osteosarcoma is the most common primary bone malignancy in children
      and young adults. Increasing results suggest that discovery of microRNAs (miRNAs)
      might provide a novel therapeutical target for osteosarcoma. METHODS: MiR-182
      expression level in osteosarcoma cell lines and tissues were assayed by qRT-PCR.
      MiRNA mimics or inhibitor were transfected for up-regulation or down-regulation
      of miR-182 expression. Cell function was assayed by CCK8, migration assay and
      invasion assay. The target genes of miR-182 were predicated by bioinformatics
      algorithm (TargetScan Human). RESULTS: MiR-182 was down-regulated in osteosarcoma
      tissues and cell lines. Overexpression of miR-182 inhibited tumor growth,
      migration and invasion. Subsequent investigation revealed that TIAM1 was a direct
      and functional target of miR-182 in osteosarcoma cells. Overexpression of miR-182
      impaired TIAM1-induced inhibition of proliferation and invasion in osteosarcoma
      cells. CONCLUSIONS: Down-expression of miR-182 in osteosarcoma promoted tumor
      growth, migration and invasion by targeting TIAM1. MiR-182 might act as a tumor
      suppressor gene whose down-regulation contributes to the progression and
      metastasis of osteosarcoma, providing a potential therapy target for osteosarcoma
      patients.

PMID- 25973949
TI  - Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal
      Infection.
AB  - Streptococcus pneumoniae accounts for more deaths worldwide than any other single
      pathogen through diverse disease manifestations including pneumonia, sepsis and
      meningitis. Life-threatening acute cardiac complications are more common in
      pneumococcal infection compared to other bacterial infections. Distinctively,
      these arise despite effective antibiotic therapy. Here, we describe a novel
      mechanism of myocardial injury, which is triggered and sustained by circulating
      pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we
      demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient
      mutants induced elevation of circulating cardiac troponins (cTns), well
      recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels
      linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels
      were significantly higher in non-surviving than in surviving mice. These cTn
      levels were significantly reduced by administration of PLY-sequestering
      liposomes. Intravenous injection of purified PLY, but not a non-pore forming
      mutant (PdB), induced substantial increase in cardiac troponins to suggest that
      the pore-forming activity of circulating PLY is essential for myocardial injury
      in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial
      inflammatory changes but apoptosis was not detected. Exposure of cultured
      cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte
      contractile dysfunction and death, which was exacerbated by further PLY release
      following antibiotic treatment. We found that high PLY doses induced extensive
      cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations
      triggered profound calcium influx and overload with subsequent membrane
      depolarization and progressive reduction in intracellular calcium transient
      amplitude, a key determinant of contractile force. This was coupled to activation
      of signalling pathways commonly associated with cardiac dysfunction in clinical
      and experimental sepsis and ultimately resulted in depressed cardiomyocyte
      contractile performance along with rhythm disturbance. Our study proposes a
      detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and
      highlights the major translational potential of targeting circulating PLY to
      protect against cardiac complications during pneumococcal infections. 

PMID- 25973951
TI  - HIF-1 Alpha Regulates the Response of Primary Sarcomas to Radiation Therapy
      through a Cell Autonomous Mechanism.
AB  - Hypoxia is a major cause of radiation resistance, which may predispose to local
      recurrence after radiation therapy. While hypoxia increases tumor cell survival
      after radiation exposure because there is less oxygen to oxidize damaged DNA, it
      remains unclear whether signaling pathways triggered by hypoxia contribute to
      radiation resistance. For example, intratumoral hypoxia can increase hypoxia
      inducible factor 1 alpha (HIF-1alpha), which may regulate pathways that
      contribute to radiation sensitization or radiation resistance. To clarify the
      role of HIF-1alpha in regulating tumor response to radiation, we generated a
      novel genetically engineered mouse model of soft tissue sarcoma with an intact or
      deleted HIF-1alpha. Deletion of HIF-1alpha sensitized primary sarcomas to
      radiation exposure in vivo. Moreover, cell lines derived from primary sarcomas
      lacking HIF-1alpha, or in which HIF-1alpha was knocked down, had decreased
      clonogenic survival in vitro, demonstrating that HIF-1alpha can promote radiation
      resistance in a cell autonomous manner. In HIF-1alpha-intact and -deleted sarcoma
      cells, radiation-induced reactive oxygen species, DNA damage repair and
      activation of autophagy were similar. However, sarcoma cells lacking HIF-1alpha
      had impaired mitochondrial biogenesis and metabolic response after irradiation,
      which might contribute to radiation resistance. These results show that HIF
      1alpha promotes radiation resistance in a cell autonomous manner. 

PMID- 25973952
TI  - Time and Cell Type Dependency of Survival Responses in Co-cultured Tumor and
      Fibroblast Cells after Exposure to Modulated Radiation Fields.
AB  - Advanced radiotherapy techniques such as intensity-modulated radiation therapy
      (IMRT) achieve high levels of conformity to the target volume through the
      sequential delivery of highly spatially and temporally modulated radiation
      fields, which have been shown to impact radiobiological response. This study
      aimed to characterize the time and cell type dependency of survival responses to
      modulated fields using single cell type (SCT) and mixed cell type (MCT) co
      culture models of transformed fibroblast (AG0-1522b) cells, prostate (DU-145) and
      lung (H460) cancer cells. In SCT cultures, in-field responses showed no
      significant time dependency while out-of-field responses occurred early, and
      plateaued 6 h after irradiation in both DU-145 and H460 cells. Under modulated
      beam configurations MCT co-cultures showed cell-specific, differential out-of
      field responses depending on the irradiated in-field and responding out-of-field
      cell type. The observed differential out-of-field responses may be due to the
      genetic background of the cells, in particular p53 status, which has been shown
      to mediate radiation-induced bystander effects (RIBEs). These data provide
      further insight into the radiobiological parameters that influence out-of-field
      responses, which have potential implications for advanced radiotherapy modalities
      and may provide opportunities for biophysical optimization in radiotherapy
      treatment planning. 

PMID- 25973953
TI  - More Caution Required for Iatrogenic Short QT: Additional Concerns on QTc
      Shortened by Testosterone Treatment.

PMID- 25973954
TI  - Changes in Plasma Copeptin Levels during Hemodialysis: Are the Physiological
      Stimuli Active in Hemodialysis Patients?
AB  - OBJECTIVES: Plasma levels of copeptin, a surrogate marker for the vasoconstrictor
      hormone arginine vasopressin (AVP), are increased in hemodialysis patients.
      Presently, it is unknown what drives copeptin levels in hemodialysis patients. We
      investigated whether the established physiological stimuli for copeptin release,
      i.e. plasma osmolality, blood volume and mean arterial pressure (MAP), are
      operational in hemodialysis patients. METHODS: One hundred and eight prevalent,
      stable hemodialysis patients on a thrice-weekly dialysis schedule were studied
      during hemodialysis with constant ultrafiltration rate and dialysate conductivity
      in this observational study. Plasma levels of copeptin, sodium, MAP, and blood
      volume were measured before, during and after hemodialysis. Multivariate analysis
      was used to determine the association between copeptin (dependent variable) and
      the physiological stimuli plasma sodium, MAP, excess weight as well as NT-pro-BNP
      immediately prior to dialysis and between copeptin and changes of plasma sodium,
      MAP and blood volume with correction for age, sex and diabetes during dialysis
      treatment. RESULTS: Patients were 63 +/- 15.6 years old and 65% were male. Median
      dialysis vintage was 1.6 years (IQR 0.7-4.0). Twenty-three percent of the
      patients had diabetes and 82% had hypertension. Median predialysis copeptin
      levels were 141.5 pmol/L (IQR 91.0-244.8 pmol/L). Neither predialysis plasma
      sodium levels, nor NT-proBNP levels, nor MAP were associated with predialysis
      copeptin levels. During hemodialysis, copeptin levels rose significantly (p<0.01)
      to 163.0 pmol/L (96.0-296.0 pmol/L). Decreases in blood volume and MAP were
      associated with increases in copeptin levels during dialysis, whereas there was
      no significant association between the change in plasma sodium levels and the
      change in copeptin levels. CONCLUSIONS: Plasma copeptin levels are elevated
      predialysis and increase further during hemodialysis. Volume stimuli, i.e.
      decreases in MAP and blood volume, rather than osmotic stimuli, are associated
      with change in copeptin levels during hemodialysis.

PMID- 25973955
TI  - Functional profiling in Streptococcus mutans: construction and examination of a
      genomic collection of gene deletion mutants.
AB  - A collection of tagged deletion mutant strains was created in Streptococcus
      mutans UA159 to facilitate investigation of the aciduric capability of this oral
      pathogen. Gene-specific barcoded deletions were attempted in 1432 open reading
      frames (representing 73% of the genome), and resulted in the isolation of 1112
      strains (56% coverage) carrying deletions in distinct non-essential genes. As S.
      mutans virulence is predicated upon the ability of the organism to survive an
      acidic pH environment, form biofilms on tooth surfaces, and out-compete other
      oral microflora, we assayed individual mutant strains for the relative fitness of
      the deletion strain, compared with the parent strain, under acidic and oxidative
      stress conditions, as well as for their ability to form biofilms in glucose- or
      sucrose-containing medium. Our studies revealed a total of 51 deletion strains
      with defects in both aciduricity and biofilm formation. We have also identified
      49 strains whose gene deletion confers sensitivity to oxidative damage and
      deficiencies in biofilm formation. We demonstrate the ability to examine
      competitive fitness of mutant organisms using the barcode tags incorporated into
      each deletion strain to examine the representation of a particular strain in a
      population. Co-cultures of deletion strains were grown either in vitro in a
      chemostat to steady-state values of pH 7 and pH 5 or in vivo in an animal model
      for oral infection. Taken together, these data represent a mechanism for
      assessing the virulence capacity of this pathogenic microorganism and a resource
      for identifying future targets for drug intervention to promote healthy oral
      microflora.

PMID- 25973956
TI  - Allele-specific imbalance mapping at human orthologs of mouse susceptibility to
      colon cancer (Scc) loci.
AB  - Colorectal cancer (CRC) can be classified into different types. Chromosomal
      instable (CIN) colon cancers are thought to be the most common type of colon
      cancer. The risk of developing a CIN-related CRC is due in part to inherited risk
      factors. Genome-wide association studies have yielded over 40 single nucleotide
      polymorphisms (SNPs) associated with CRC risk, but these only account for a
      subset of risk alleles. Some of this missing heritability may be due to gene-gene
      interactions. We developed a strategy to identify interacting candidate
      genes/loci for CRC risk that utilizes both linkage and RNA-seq data from mouse
      models in combination with allele-specific imbalance (ASI) studies in human
      tumors. We applied our strategy to three previously identified CRC susceptibility
      loci in the mouse that show evidence of genetic interaction: Scc4, Scc5 and
      Scc13. 525 SNPs from genes showing differential expression in the mouse and/or a
      previous role in cancer from the literature were evaluated for allele-specific
      imbalance in 194 paired human normal/tumor DNAs from CIN-related CRCs. One
      hundred three SNPs showing suggestive evidence of ASI (31 variants with
      uncorrected p values < 0.05) were genotyped in a validation set of 296 paired
      DNAs. Two variants in SNX10 (SCC13) showed significant evidence of allelic
      selection after multiple comparisons testing. Future studies will evaluate the
      role of these variants in combination with interacting genetic partners in colon
      cancer risk in mouse and humans. 

PMID- 25973957
TI  - Shaping the water crevice to accommodate the voltage sensor in a down
      conformation: a molecular dynamics simulation study.
AB  - Voltage sensor domains (VSD) of voltage-dependent ion channels share a basic
      molecular structure with a voltage-sensing phosphatase and a voltage-gated proton
      channel. The VSD senses and responds to changes in the membrane potential by
      undergoing conformational changes associated with the movement of the charged
      arginines located on the S4 segment. Although several functional and structural
      studies have provided useful information about the conformational changes in many
      ion channels, a detailed and unambiguous explanation has not been published.
      Therefore, understanding the principle of voltage-dependent gating at an atomic
      level is required. In this study, we took advantage of the available spin
      labeling electron paramagnetic resonance spectrometry data and computational
      methods to investigate the structure and dynamic properties of the Up-state
      (activated) and Down-state (resting) conformations of the VSD by means of all
      atom molecular dynamics (MD) simulations. The MD results of the Down conformation
      determined in bilayers with and without lipid phosphates both revealed a
      different shape of the aqueous crevice, in which more water molecules surround
      and fill the intracellular crevice in its Down state than in its Up state. The
      solvent accessible surface within the crevice has a complementary shape that can
      account for water-mediated interactions between the voltage sensor and the lipid
      bilayer. The results support the previously reported experimental data. 

PMID- 25973958
TI  - Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic
      nephropathy.
AB  - AIM: We aimed to determine whether serum SPON2 is a useful biomarker in the
      detection of Diabetic Nephropathy (DN) and to compare serum SPON2 levels with 24
      hour urinary albumin excretion rate (UAER) in patients with DN at different
      stages. METHODS: The cohort included 80 adult patients with T2D and 20 healthy
      controls. The patients with T2D were divided into four groups according to UAER
      and serum creatinine (sCr) levels. Group 1 consisted of patients with
      normoalbuminuria (n = 20), Group 2 with microalbuminuria (n = 20), Group 3 with
      macroalbuminuria (n = 20) and Group 4 with albuminuria and sCr > 1.5 mg/dL (n =
      20). RESULTS: There were no significant differences between the groups in terms
      of demographic data, C-reactive protein, HbA1c, lipids, serum uric acid levels
      and leukocyte counts. SPON2 levels were observed to increase linearly with
      increasing severity of diabetic nephropathy levels. The SPON2 levels of Group 4
      were significantly higher than Group 1 and the controls, and SPON2 levels of
      Group 3 were significantly higher than Group 1. Blood urea nitrogen, creatinine
      and UAER were significantly positively correlated with SPON2; serum total protein
      and calcium levels were negatively correlated with SPON2 in patients with DN.
      CONCLUSION: We observed a linear and significant increase in SPON2 levels of
      patients with T2D as the stage of DN increased, but serum SPON2 level was not as
      effective as microalbuminuria in reflecting nephropathy. Also, serum SPON2 level
      was not as good as urine and tissue levels of SPON2 in detection of renal damage
      in DN.

PMID- 25973961
TI  - Folding thermodynamics of beta-hairpins studied by replica-exchange molecular
      dynamics simulations.
AB  - We study the differences in folding stability of beta-hairpin peptides, including
      GB1 hairpin and a point mutant GB1 K10G, as well as tryptophan zippers (TrpZips):
      TrpZip1, TrpZip2, TrpZip3-1, and TrpZip4. By performing replica-exchange
      molecular dynamics simulations with Amber03* force field (a modified version of
      Amber ff03) in explicit solvent, we observe ab initio folding of all the peptides
      except TrpZip3-1, which is experimentally known to be the least stable among the
      peptides studied here. By calculating the free energies of unfolding of the
      peptides at room temperature and folding midpoint temperatures for thermal
      unfolding of peptides, we find that TrpZip4 and GB1 K10G peptides are the most
      stable beta-hairpins followed by TrpZip1, GB1, and TrpZip2 in the given order.
      Hence, the proposed K10G mutation of GB1 peptide results in enhanced stability
      compared to wild-type GB1. An important goal of our study is to test whether
      simulations with Amber 03* model can reproduce experimentally predicted folding
      stability differences between these peptides. While the stabilities of GB1 and
      TrpZip1 yield close agreement with experiment, TrpZip2 is found to be less stable
      than predicted by experiment. However, as heterogenous folding of TrpZip2 may
      yield divergent thermodynamic parameters by different spectroscopic methods,
      mismatching of results with previous experimental values are not conclusive of
      model shortcomings. For most of the cases, molecular simulations with Amber03*
      can successfully reproduce experimentally known differences between the mutated
      peptides, further highlighting the predictive capabilities of current state-of
      the-art all-atom protein force fields.

PMID- 25973959
TI  - Membrane proteins in their native habitat as seen by solid-state NMR
      spectroscopy.
AB  - Membrane proteins play many critical roles in cells, mediating flow of material
      and information across cell membranes. They have evolved to perform these
      functions in the environment of a cell membrane, whose physicochemical properties
      are often different from those of common cell membrane mimetics used for
      structure determination. As a result, membrane proteins are difficult to study by
      traditional methods of structural biology, and they are significantly
      underrepresented in the protein structure databank. Solid-state Nuclear Magnetic
      Resonance (SSNMR) has long been considered as an attractive alternative because
      it allows for studies of membrane proteins in both native-like membranes composed
      of synthetic lipids and in cell membranes. Over the past decade, SSNMR has been
      rapidly developing into a major structural method, and a growing number of
      membrane protein structures obtained by this technique highlights its potential.
      Here we discuss membrane protein sample requirements, review recent progress in
      SSNMR methodologies, and describe recent advances in characterizing membrane
      proteins in the environment of a cellular membrane. 

PMID- 25973960
TI  - Town mouse or country mouse: identifying a town dislocation effect in Chinese
      urbanization.
AB  - Understanding urbanization and evaluating its impact are vital for formulating
      global sustainable development. The results obtained from evaluating the impact
      of urbanization, however, depend on the kind of measurement used. With the goal
      of increasing our understanding of the impact of urbanization, we developed
      direct and indirect subjective indicators to measure how people assess their
      living situation. The survey revealed that the projected endorsements and
      perceived social ambiance of people toward living in different types of
      settlements did not improve along with the urbanization level in China. The
      assessment scores from the city dwellers were not significantly different from
      those from the country areas and, more surprisingly, both were significantly
      higher than the assessment scores of the town dwellers, which we had expected to
      fall between the assessment scores of the country and city dwellers. Instead
      their scores were the lowest. We dubbed this V-shaped relationship the "town
      dislocation effect." When searching for a potential explanation for this effect,
      we found additional town dislocation effects in social support, loss aversion,
      and receptivity toward genetically modified food. Further analysis showed that
      only social support mediated the relationship between the three tiers of
      settlements (cities, country areas, and towns) and the subjective indicator. The
      projected endorsements yielded significant subjective assessments that could
      enhance our understanding of Chinese urbanization. Towns posed specific problems
      that require special attention. 

PMID- 25973969
TI  - The Role of Age in Moderating the Association Between Disability and Light
      Intensity Physical Activity.
AB  - PURPOSE: There's a lack of evidence on the association between light-intensity
      physical activity and disability. This study examines the relationships in
      activity by self-reported physical function in five domains (i.e., activities of
      daily living [ADL], instrumental ADL, leisure activities, lower extremity, and
      general activities), and whether this association varies by age. DESIGN: Cross
      sectional. SETTING: Data from National Health and Nutrition Examination Survey
      2003-2004 and 2005-2006 waves. SUBJECTS: Participants included 5700 men and women
      ages 20 to 85 years. MEASURES: Difficulty with various activities was measured
      with the Physical Functioning Questionnaire, accelerometer-measured physical
      activity, demographics, and self-rated health. ANALYSIS: Ordinary least squares
      regression models were run to examine the relationship between physical function
      in each domain, light-intensity activity, and the moderating effect of age.
      Analyses controlled for body mass index, moderate-to-vigorous-intensity activity,
      self-reported health, accelerometer wear time, and gender. RESULTS: Little
      variation was seen in light-intensity physical activity among younger adults
      regardless of disability status. Older adults reporting difficulty with
      activities engaged in significantly less light-intensity physical activity
      compared to those with no disability (271.8 vs. 316.5 minutes). Age significantly
      moderated the association between light-intensity physical activity and leisure
      activities (p = .048), and lower extremity mobility (p = .039). Age did not
      moderate other domains of disability. CONCLUSION: Younger age may be protective
      regarding the influence of disability on light-intensity activity. In addition,
      disability may be more debilitating for some older individuals. Interventions to
      increase light-intensity activity should aim to address disability at all ages,
      with increased attention for older adults.

PMID- 25973966
TI  - Community Lenses Revealing the Role of Sociocultural Environment on Physical
      Activity.
AB  - PURPOSE: To identify perceptions of how sociocultural environment enabled and
      hindered physical activity (PA) participation. DESIGN: Community-based
      participatory research. SETTING: Two semirural and two urban communities located
      in Alberta, Canada. PARTICIPANTS: Thirty-five people (74.3% females, 71.4% aged
      25-64 years) across the four communities. METHOD: PhotoVoice activities occurred
      over 3 months during the spring of 2009. Participants were asked to document
      perceived environmental attributes that might foster or inhibit PA in their
      community. Photographs and narratives were shared in one-on-one interviews. Line
      by-line coding of the transcripts was independently conducted by two researchers
      using an inductive approach. Codes were arranged into themes and subthemes, which
      were then organized into the Analysis Grid for Environments Linked to Obesity
      (ANGELO) framework. RESULTS: Six main themes (accompanied by subthemes) emerged:
      sociocultural aesthetics, safety, social involvement, PA motivation, cultural
      ideas of recreation, and car culture. Representative quotes and photographs
      illustrate enablers and obstacles identified by participants. CONCLUSION: This
      PhotoVoice study revealed how aspects of participants' sociocultural environments
      shaped their decisions to be physically active. Providing more PA resources is
      only one step in the promotion of supportive environments. Strategies should also
      account for the beautification and maintenance of communities, increasing
      feelings of safety, enhancement of social support among community members,
      popularization of PA, and mitigating car culture, among others.

PMID- 25973970
TI  - Child and Caregiver Attitudes About Sports Drinks and Weekly Sports Drink Intake
      Among U.S. Youth.
AB  - PURPOSE: To examine caregiver and youth attitudes about sports drinks (SDs) and
      the association of those attitudes with youth SD intake. DESIGN: Study design was
      cross-sectional. The online YouthStyles survey was sent to youth (ages 12-17
      years) whose caregivers completed the online Summer ConsumerStyles survey for
      adults. SETTING: The 2011 Styles survey data comprised the setting. SUBJECTS: The
      sample was composed of 815 U.S. caregiver-youth dyads. MEASURES: The outcome
      variable is youth SD consumption, and exposure variables are youth and
      caregivers' attitudes that SDs are healthy for children, and caregivers' attitude
      that children need SDs for hydration. Covariates are youth demographic and
      physical activity variables. ANALYSIS: Multivariable logistic regression was used
      to estimate adjusted odds ratios (ORs) for youth SD consumption one or more times
      per week after controlling for covariates. RESULTS: About one in five youth
      consumed SDs one or more times per week. Caregiver attitudes about the
      healthfulness of SDs and children's need of SDs for hydration both significantly
      differed by race and caregiver education level. The odds of youth SD consumption
      one or more times per week were significantly higher among youth of caregivers
      who agreed that SDs are good, healthy drinks for children (OR, 2.72 vs.
      disagreed) and among youth of caregivers who agreed that children need SDs for
      hydration (OR, 3.15 vs. disagreed). Youth attitude about SD healthfulness was not
      associated with intake. CONCLUSION: Caregivers, particularly minority and less
      educated caregivers, may need more education about SD use.

PMID- 25973971
TI  - Diastereodivergent Catalytic Asymmetric Michael Addition of 2-Oxindoles to
      alpha,beta-Unsaturated Ketones by Chiral Diamine Catalysts.
AB  - A diastereodivergent catalytic asymmetric Michael addition of 2-oxindoles to
      alpha,beta-unsaturated ketones has been successfully developed with two
      complementary chiral diamine catalysts, affording chiral 3,3-disubstituted
      oxindoles with two adjacent chiral centers. Diastereodivergence has been realized
      through modifying substrates and utilizing different catalysts. Either anti-or
      syn-configured products possessing vicinal quaternary and tertiary stereogenic
      centers were produced with high enantioselectivities. 

PMID- 25973972
TI  - Computed Cerenkov luminescence yields for radionuclides used in biology and
      medicine.
AB  - Cerenkov luminescence imaging is an emerging biomedical imaging modality that
      takes advantage of the optical Cerenkov photons emitted following the decay of
      radionuclides in dielectric media such as tissue. Cerenkov radiation potentially
      allows many biomedically-relevant radionuclides, including all positron-emitting
      radionuclides, to be imaged in vivo using sensitive CCD cameras. Cerenkov
      luminescence may also provide a means to deliver light deep inside tissue over a
      sustained period of time using targeted radiotracers. This light could be used
      for photoactivation, including photorelease of therapeutics, photodynamic therapy
      and photochemical internalization. Essential to assessing the feasibility of
      these concepts, and the design of instrumentation designed for detecting Cerenkov
      radiation, is an understanding of the light yield of different radionuclides in
      tissue. This is complicated by the dependence of the light yield on refractive
      index and the volume of the sample being interrogated. Using Monte Carlo
      simulations, in conjunction with step-wise use of the Frank-Tamm equation, we
      studied forty-seven different radionuclides and show that Cerenkov light yields
      in tissue can be as high as a few tens of photons per nuclear decay for a
      wavelength range of 400-800 nm. The dependency on refractive index and source
      volume is explored, and an expression for the scaling factor necessary to compute
      the Cerenkov yield in any arbitrary spectral band is given. This data will be of
      broad utility in guiding the application of Cerenkov radiation emitted from
      biomedical radionuclides.

PMID- 25973973
TI  - Correction: RNAi-Dependent and Independent Control of LINE1 Accumulation and
      Mobility in Mouse Embryonic Stem Cells.

PMID- 25973974
TI  - Ultrathin Printable Graphene Supercapacitors with AC Line-Filtering Performance.
AB  - Ultrathin printable graphene supercapacitors are demonstrated, based on solution
      processed electrochemically exfoliated graphene hybrid films on an ultrathin
      poly(ethylene terephthalate) substrate, exhibiting an unprecedented volumetric
      capacitance of 348 F cm(-3) , an ultrahigh scan rate of 2000 V s(-1) , and AC
      line-filtering performance. 

PMID- 25973975
TI  - Geographic variation in the Pine Barrens Treefrog (Hyla andersonii): concordance
      of genetic, morphometric and acoustic signal data.
AB  - Delimiting species is important to every subfield in biology. Templeton's
      cohesion species concept uses genetic and ecological exchangeability to identify
      sets of populations that ought to be considered as the same species, and the lack
      of exchangeability helps determine which populations can be grouped as
      evolutionarily significant units (ESU) in conservation science. However, previous
      work assessing genetic and ecological interchangeability among populations has
      been limited in scope. Here, we provide a method for assessing exchangeability
      that incorporates multiple, independent lines of multivariate evidence in
      genetic, behavioural and morphological data. We use this approach to assess
      exchangeability across three disjunct groups of populations of the Pine Barrens
      Treefrog (Hyla andersonii) from the eastern United States. This species is
      considered threatened by each state in which it occurs and conservation
      management of this taxon requires a clearer understanding of how populations in
      these three regions may differ from one another. We find a strikingly concordant
      pattern in which the first axis of variation for each of the three types of data
      distinguishes populations along a latitudinal gradient and the second axis
      distinguishes the set of populations occurring in the Carolinas from those
      occurring in the New Jersey and Florida/Alabama regions. We know of no comparable
      data set that displays such concordance among different types of data across so
      large a geographic range. The overlap in trait values (i.e. exchangeability)
      between neighbouring regions, however, is substantial in all three types of data,
      which supports continued consideration of this taxon as a single species. 

PMID- 25973976
TI  - Pragmatic detection of anxiety and depression in a prospective cohort of voice
      outpatient clinic attenders.
AB  - OBJECTIVE: To evaluate diagnostic performance of the emotional domain of the
      VoiSS questionnaire compared with the Hospital Anxiety and Depression Scale
      (HADS). DESIGN: Cross-sectional questionnaire study. SETTING: Tertiary referral
      centre voice clinic. PARTICIPANTS: 210 consecutive voice clinic patients. MAIN
      OUTCOME MEASURES: Screening with VoiSS and HADS questionnaires. Paired
      comparison, correlation, multinomial logistic regression and receiver-operating
      characteristic (ROC) curve analysis. RESULTS: A total of 177 returned complete
      data sets. Ninety-six patients (54.2%) had functional dysphonia, and 81 (45.8%)
      had organic laryngeal disorders. Mean total VoiSS score = 39.7/120 (standard
      deviation (sd) 22.2). Mean emotional VoiSS subscale = 7.6/22 (sd 7.5). Mean HADS
      anxiety = 6.5/21 (sd 5.2) and depression mean = 7.1/21 (sd 4.8). There were 35
      (20%) borderline anxiety and/or depression scores and 30 (17%) scores considered
      positive for 'caseness'. There was strong correlation between emotional VoiSS and
      HADS anxiety (Spearman's Rho = 0.68, P < 0.001) and HADS depression (Spearman's
      Rho = 0.62, P < 0.001). ROC curve analysis exhibited significant association
      between emotional VoiSS and HADS 'caseness' (area under curve = 0.88). In
      addition, functional dysphonia patients had lower mean VoiSS and HADS scores than
      patients with identifiable laryngeal abnormalities. CONCLUSION: The VoiSS
      emotional subscale strongly correlates with HADS anxiety and depression scores
      and could be used as a measure of psychological distress. This could allow
      targeted psychological strategies, without additional psychometric
      questionnaires. Functional dysphonia has less association with psychological
      distress than certain organic laryngological disorders.

PMID- 25973978
TI  - Effect of Surface Wettability on Crack Dynamics and Morphology of Colloidal
      Films.
AB  - The effect of surface wettability on the dynamics of crack formation and their
      characteristics are examined during the drying of aqueous colloidal droplets (1
      MUL volume) containing nanoparticles (53 nm mean particle diameter, 1 w/w %).
      Thin colloidal films, formed during drying, rupture as a result of the
      evaporation-induced capillary pressure and exhibit microscopic cracks. The crack
      initiation and propagation velocity as well as the number of cracks are
      experimentally evaluated for substrates of varying wettability and correlated to
      their wetting nature. Atomic force and scanning electron microscopy are used to
      examine the region in the proximity of the crack including the particle
      arrangements near the fracture zone. The altered substrate-particle Derjaguin
      Landau-Verwey-Overbeek (DLVO) interactions, as a consequence of the changed
      wettability, are theoretically evaluated and found to be consistent with the
      experimental observations. The resistance of the film to cracking is found to
      depend significantly on the substrate surface energy and quantified by the
      critical stress intensity factor, evaluated by analyzing images obtained from
      confocal microscopy. The results indicate the possibility of controlling crack
      dynamics and morphology by tuning the substrate wettability. 

PMID- 25973977
TI  - Large-scale patterns of turnover and Basal area change in Andean forests.
AB  - General patterns of forest dynamics and productivity in the Andes Mountains are
      poorly characterized. Here we present the first large-scale study of Andean
      forest dynamics using a set of 63 permanent forest plots assembled over the past
      two decades. In the North-Central Andes tree turnover (mortality and recruitment)
      and tree growth declined with increasing elevation and decreasing temperature. In
      addition, basal area increased in Lower Montane Moist Forests but did not change
      in Higher Montane Humid Forests. However, at higher elevations the lack of net
      basal area change and excess of mortality over recruitment suggests negative
      environmental impacts. In North-Western Argentina, forest dynamics appear to be
      influenced by land use history in addition to environmental variation. Taken
      together, our results indicate that combinations of abiotic and biotic factors
      that vary across elevation gradients are important determinants of tree turnover
      and productivity in the Andes. More extensive and longer-term monitoring and
      analyses of forest dynamics in permanent plots will be necessary to understand
      how demographic processes and woody biomass are responding to changing
      environmental conditions along elevation gradients through this century. 

PMID- 25973980
TI  - Antisynthetase syndrome: a review of etiopathogenesis, diagnosis and management.
AB  - Antisynthetase syndrome is a group of closely related rare diseases which
      clinically manifest with inflammatory myopathies, interstitial lung disease,
      inflammatory arthritis, skin hyperkeratosis (mechanic's hands) and Raynaud
      phenomenon. The pathophysiology of antisynthetase syndrome is not entirely
      understood, but genetic predisposition, viral infections and medication use may
      play a role. Certain antisynthetase antibodies are associated with various
      clinical presentations and a lower burden of inflammatory myopathies. Patients
      with antisynthetase syndrome have a worse prognosis than patients with pure
      inflammatory myopathies mainly because of interstitial lung disease. Future
      research should further investigate the pathogenesis of antisynthetase syndrome
      which could identify new therapeutic targets. It will be also important to study
      whether patients with AS are at increased risk of cancer and whether certain
      antisynthetase antibodies have any association with the risk of malignancy.

PMID- 25973981
TI  - Multiple Targets for Drug-Induced Mitochondrial Toxicity.
AB  - Mitochondrial toxicity is rapidly gaining the interest of researchers and
      practitioners as a prominent liability in drug discovery and development,
      accounting for a growing proportion of preclinical drug attrition and post-market
      withdrawals or black box warnings by the U.S. FDA. To date, the focus of
      registries of drugs that elicit mitochondrial toxicity has been largely
      restricted to those that either inhibit the mitochondrial electron transport
      chain (ETC) or uncouple mitochondrial oxidative phosphorylation. Less appreciated
      are the toxicities that are secondary to the drug affecting either the molecular
      regulation, assembly or incorporation of the ETC into the inner mitochondrial
      membrane or those that limit substrate availability. The current article
      describes the complexities of molecular events and biochemical pathways required
      to sustain mitochondrial fidelity and substrate homeostasis with examples of
      drugs that interfere which the various pathways. The principal objective of this
      review is to shed light on the broader scope of drug-induced mitochondrial
      toxicities and how these secondary targets may account for a large portion of
      drug failures. 

PMID- 25973979
TI  - Long-term safety of oral nucleos(t)ide analogs for patients with chronic
      hepatitis B: A cohort study of 53,500 subjects.
AB  - Widespread and long-term use of oral nucleos(t)ide analogs (NAs) to treat chronic
      hepatitis B (CHB) brings about safety data in a real-life setting. We aimed to
      determine the risks of renal and bone side effects in patients receiving or who
      have received NAs as CHB treatment. A territory-wide cohort study using the
      database from Hospital Authority, the major provider of medical services in Hong
      Kong, was conducted. We identified CHB patients by International Classification
      of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed
      between 2000 and 2012. The primary events were renal (incident renal failure and
      renal replacement therapy [RRT]) and bone events (incident hip, vertebral, and
      all fractures). A 3-year landmark analysis was used to evaluate the relative risk
      of primary outcome in patients with or without NA treatment. A total of 53,500
      CHB patients (46,454 untreated and 7,046 treated), who were event free for 3
      years, were included in the analysis. At a median follow-up of 4.9 years, chronic
      renal failure, RRT, all fractures, hip fractures, and vertebral fractures
      occurred in 0.6%, 0.2%, 0.7%, 0.1%, and 0.1% of untreated subjects and 1.4%,
      0.7%, 1.3%, 0.2%, and 0.2% of treated subjects. After propensity score weighting,
      NA therapy did not increase the risk of any of the events (hazard ratios [HRs]
      ranged from 0.79 to 1.31; P = 0.225-0.887). Exposure to nucleotide analogues,
      compared with nucleoside analogs, increased the risk of hip fracture (HR = 5.69;
      95% confidence interval: 1.98-16.39; P = 0.001), but not other events (HR = 0.58
      1.44; P = 0.202-0.823). CONCLUSIONS: NA treatment does not increase the risk of
      renal and bone events in general. Nucleotide analogs may increase the risk of hip
      fracture, but the overall event rate is low.

PMID- 25973982
TI  - Mitochondrial Mechanisms of Metabolic Reprogramming in Proliferating Cells.
AB  - Mitochondria are responsible for coordinating cellular energy production in the
      vast majority of somatic cells, and every cell type in a specific state can have
      a distinct metabolic signature. The metabolic requirements of cells from
      different tissues changes as they proliferate/differentiate, and cellular
      metabolism must match these demands. Proliferating cells, namely cancer cells and
      stem cells, tend to prefer glycolysis rather than a more oxidative metabolism.
      This preference has been exploited for the improvement of new biotechnological
      and therapeutic applications. In this review, we describe mitochondrial dynamics
      and energy metabolism modulation during nuclear reprogramming of somatic cells,
      which will be essential for the development and optimization of new protocols for
      regenerative medicine, disease modeling and toxicological screens involving
      patient-specific reprogrammed cells.

PMID- 25973983
TI  - Regulation of Mitochondrial Function and its Impact in Metabolic Stress.
AB  - Mitochondria are key players in the maintenance of cellular homeostasis, as they
      generate ATP via OXPHOS. As such, disruption in mitochondrial homeostasis is
      closely associated with disease states, caused by subtle alterations in the
      function of tissues or by major defects, particularly evident in tissues with
      high metabolic demands. Adaptations in mitochondrial copy number or mitochondrial
      mass, and the induction of genes implicated in OXPHOS or in intermediary
      metabolism as well, depend on the balanced contribution of both the nuclear and
      mitochondrial genomes. This forms a biogenesis program, controlled by several
      nuclear factors that act coordinately and in a categorized manner. Dynamic
      changes in mitochondrial regulators are associated with post-translational
      modifications mediated by metabolic sensors, such as SIRT1 and AMPK. Nrf2, which
      induces an antioxidant protective response against oxidative stress, also
      modulates bioenergetic function and metabolism. Additionally, the stability of
      mitochondrial transcripts is decreased by miRNA detected in the mitochondria,
      thus affecting the bioenergetic capacity of the cell. However, mitochondrial
      adaptation to metabolic demands is also dependent on the removal of damaged
      mitochondria (mitophagy) and fission/fusion events of the mitochondrial network. 

PMID- 25973984
TI  - Effect of Microwave Heating on Phytosterol Oxidation.
AB  - The oxidative stability of phytosterols during microwave heating was evaluated.
      Two different model systems (a solid film made with a phytosterol mixture (PSF)
      and a liquid mixture of phytosterols and triolein (1:100, PS + TAG
      (triacylglycerol))) were heated for 1.5, 3, 6, 12, 20, and 30 min at 1000 W. PS
      degraded faster when they were microwaved alone than in the presence of TAG,
      following a first-order kinetic model. Up to 6 min, no phytosterol oxidation
      products (POPs) were generated in both systems. At 12 min of heating, the POP
      content reached a higher level in PSF (90.96 MUg/mg of phytosterols) than in PS +
      TAG (22.66 MUg/mg of phytosterols), but after 30 min of treatment, the opposite
      trend was observed. 7-Keto derivates were the most abundant POPs in both systems.
      The extent of phytosterol degradation depends on both the heating time and the
      surrounding medium, which can impact the quality and safety of the food product
      destined to microwave heating/cooking. 

PMID- 25973985
TI  - Endoscopic Resection for Benign Parotid Tumor Through a Cosmetic Retroauricular
      Incision with Water Sac Establishing Operative Space: A New Approach.
AB  - PURPOSE: To develop a new approach of endoscopic resection for benign parotid
      tumor through a cosmetic retroauricular incision with a water sac establishing
      the operative space. MATERIALS AND METHODS: Fifty-eight patients with benign
      parotid superficial lobe tumor were randomly assigned to an endoscopic (29
      patients) or a conventional (29 patients) surgery group. The maximum diameter of
      the tumors was 6 cm. The subjective satisfaction scores with the incision scar,
      incision length, operative bleeding volume, postoperative complications, and
      recurrence rate were compared between the groups. RESULTS: All operations were
      successfully performed. The endoscopic incision length (4.3+/-0.5 cm), bleeding
      volume (26.6+/-10.4 mL), and incidence of temporary facial paresis (6.9%)
      differed from the conventional surgery group (P<.05). The scars were almost
      invisible behind the ear. The mean patient satisfaction score was 8.9+/-0.7 in
      the endoscopic surgery group and 6.7+/-1.8 in the conventional surgery group
      (P<.05). Otherwise, Frey's syndrome and salivary fistula incidences were 3.4%
      (1/29) and 3.4% (1/29), respectively, in the endoscopic surgery group, which was
      not significantly different from the conventional surgery group (P>.05). No tumor
      recurrence was found during the 3-72 months of follow-up. CONCLUSIONS: Endoscopic
      resection through a cosmetic retroauricular incision with a water sac
      establishing operative space is a feasible method for treatment of benign parotid
      superficial lobe tumor. Its main advantages are that the small and concealed
      operative scars improved the cosmetic results, and it provided a novel method for
      establishing the operation working space that could reduce the operative trauma.

PMID- 25973986
TI  - Screening hybridomas for anabolic androgenic steroids by steroid analog antigen
      microarray.
AB  - BACKGROUND: Currently, dozens of anabolic androgenic steroids (AAS) are forbidden
      in the World Anti-Doping Agency Prohibited List, however, despite extensive
      investigation, there are still lots of AAS without corresponding monoclonal
      antibodies. RESULTS: A steroid analog antigen microarray made up of ten AAS was
      fabricated to screen the hybridoma and it was found an original unsuccessful
      clone turned out to be a candidate anti-boldenone antibody, without any cross
      reactions with endogenous AAS or 44 different AAS standard reference materials
      tested. CONCLUSION: Our findings suggested that steroid analog antigen microarray
      could be a promising tool to screen and characterize new applications of
      antibodies for structure analogs, and this also exhibits the potential to fast
      identify effective epitopes of hybridomas in a single assay.

PMID- 25973987
TI  - Applying data envelopment analysis to preventive medicine: a novel method for
      constructing a personalized risk model of obesity.
AB  - Data envelopment analysis (DEA) is a method of operations research that has not
      yet been applied in the field of obesity research. However, DEA might be used to
      evaluate individuals' susceptibility to obesity, which could help establish
      effective risk models for the onset of obesity. Therefore, we conducted this
      study to evaluate the feasibility of applying DEA to predict obesity, by
      calculating efficiency scores and evaluating the usefulness of risk models. In
      this study, we evaluated data from the Takahata study, which was a population
      based cohort study (with a follow-up study) of Japanese people who are >40 years
      old. For our analysis, we used the input-oriented Charnes-Cooper-Rhodes model of
      DEA, and defined the decision-making units (DMUs) as individual subjects. The
      inputs were defined as (1) exercise (measured as calories expended) and (2) the
      inverse of food intake (measured as calories ingested). The output was defined as
      the inverse of body mass index (BMI). Using the beta coefficients for the
      participants' single nucleotide polymorphisms, we then calculated their genetic
      predisposition score (GPS). Both efficiency scores and GPS were available for
      1,620 participants from the baseline survey, and for 708 participants from the
      follow-up survey. To compare the strengths of the associations, we used models of
      multiple linear regressions. To evaluate the effects of genetic factors and
      efficiency score on body mass index (BMI), we used multiple linear regression
      analysis, with BMI as the dependent variable, GPS and efficiency scores as the
      explanatory variables, and several demographic controls, including age and sex.
      Our results indicated that all factors were statistically significant (p < 0.05),
      with an adjusted R2 value of 0.66. Therefore, it is possible to use DEA to
      predict environmentally driven obesity, and thus to establish a well-fitted model
      for risk of obesity. 

PMID- 25973988
TI  - Elevated CO2 improves lipid accumulation by increasing carbon metabolism in
      Chlorella sorokiniana.
AB  - Supplying microalgae with extra CO2 is a promising means for improving lipid
      production. The molecular mechanisms involved in lipid accumulation under
      conditions of elevated CO2, however, remain to be fully elucidated. To understand
      how elevated CO2 improves lipid production, we performed sequencing of Chlorella
      sorokiniana LS-2 cellular transcripts during growth and compared transcriptional
      dynamics of genes involved in carbon flow from CO2 to triacylglycerol. These
      analyses identified the majority genes of carbohydrate metabolism and lipid
      biosynthesis pathways in C. sorokiniana LS-2. Under high doses of CO2 , despite
      down-regulation of most de novo fatty acid biosynthesis genes, genes involved in
      carbohydrate metabolic pathways including carbon fixation, chloroplastic
      glycolysis, components of the pyruvate dehydrogenase complex (PDHC) and
      chloroplastic membrane transporters were upexpressed at the prolonged lipid
      accumulation phase. The data indicate that lipid production is largely
      independent of de novo fatty acid synthesis. Elevated CO2 might push cells to
      channel photosynthetic carbon precursors into fatty acid synthesis pathways,
      resulting in an increase of overall triacylglycerol generation. In support of
      this notion, genes involved in triacylglycerol biosynthesis were substantially up
      regulated. Thus, elevated CO2 may influence regulatory dynamics and result in
      increased carbon flow to triacylglycerol, thereby providing a feasible approach
      to increase lipid production in microalgae. 

PMID- 25973989
TI  - A Minimal beta-Lactone Fragment for Selective beta5c or beta5i Proteasome
      Inhibitors.
AB  - Broad-spectrum proteasome inhibitors are applied as anticancer drugs, whereas
      selective blockage of the immunoproteasome represents a promising therapeutic
      rationale for autoimmune diseases. We here aimed at identifying minimal
      structural elements that confer beta5c or beta5i selectivity on proteasome
      inhibitors. Based on the natural product belactosin C, we synthesized two beta
      lactones featuring a dimethoxybenzyl moiety and either a methylpropyl (pseudo
      isoleucin) or an isopropyl (pseudo-valine) P1 side chain. Although the two
      compounds differ only by one methyl group, the isoleucine analogue is six times
      more potent for beta5i (IC50=14 nM) than the valine counterpart. Cell culture
      experiments demonstrate the cell-permeability of the compounds and X-ray
      crystallography data highlight them as minimal fragments that occupy primed and
      non-primed pockets of the active sites of the proteasome. Together, these results
      qualify beta-lactones as a promising lead-structure motif for potent nonpeptidic
      proteasome inhibitors with diverse pharmaceutical applications.

PMID- 25973990
TI  - Direct transfer of viral and cellular proteins from varicella-zoster virus
      infected non-neuronal cells to human axons.
AB  - Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon
      primary infection and Herpes zoster (shingles) following reactivation in latently
      infected neurons, is known to be fusogenic. It forms polynuclear syncytia in
      culture, in varicella skin lesions and in infected fetal human ganglia
      xenografted to mice. After axonal infection using VZV expressing green
      fluorescent protein (GFP) in compartmentalized microfluidic cultures there is
      diffuse filling of axons with GFP as well as punctate fluorescence corresponding
      to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that
      both proteins encoded by VZV genes and those of the infecting cell are
      transferred in bulk from infecting non-neuronal cells to axons. Similar transfer
      of protein to axons was observed following cell associated HSV1 infection.
      Fluorescence recovery after photobleaching (FRAP) experiments provide evidence
      that this transfer is by diffusion of proteins from the infecting cells into
      axons. Time-lapse movies and immunocytochemical experiments in co-cultures
      demonstrate that non-neuronal cells fuse with neuronal somata and proteins from
      both cell types are present in the syncytia formed. The fusogenic nature of VZV
      therefore may enable not only conventional entry of virions and capsids into
      axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic
      fusion that permits viral protein transfer to neurons in bulk. 

PMID- 25973991
TI  - Effect of ultrasound treatment on the wet heating Maillard reaction between mung
      bean [Vigna radiate (L.)] protein isolates and glucose and on structural and
      physico-chemical properties of conjugates.
AB  - BACKGROUND: The objective of this study was to determine the effect of ultrasound
      treatment on the wet heating Maillard reaction between mung bean protein isolates
      (MBPIs) and glucose, and on structural and physico-chemical properties of the
      conjugates. RESULTS: The degree of glycosylation of MBPI-glucose conjugates
      treated by ultrasound treatment and wet heating (MBPI-GUH) was higher than that
      of MBPI-glucose conjugates only treated by wet heating (MBPI-GH). Solubility,
      emulsification activity, emulsification stability and surface hydrophobicity of
      MBPI-GUH were higher than that of MBPI-GH. Grafted MBPIs had a lower content of
      alpha-helix and unordered coil, but a higher content of beta-sheet and beta-turn
      structure than MBPIs. No significant structural changes were observed in beta
      turn and random coil structure of MBPI-GUH, while alpha-helix content increased
      with ultrasonic time, and decreased at 300 W ultrasonic power with the increase
      of beta-sheet. MBPI-GUH had a less compact tertiary structure compared to MBPI-GH
      and MBPI. Grafting MBPIs with glucose formed conjugates of higher molecular
      weight, while no significant changes were observed in electrophoresis profiles of
      MBPI-GUH. CONCLUSION: Ultrasound-assisted wet heating Maillard reaction between
      MBPIs and glucose could be a promising way to improve functional properties of
      MBPIs.

PMID- 25973992
TI  - Morphogenesis of the saccus vasculosus of turbot Scophthalmus maximus: assessment
      of cell proliferation and distribution of parvalbumin and calretinin during
      ontogeny.
AB  - The ontogenesis of the saccus vasculosus (SV) of turbot Scophthalmus maximus is
      described using histological and immunohistochemical methods to assess the
      general morphology, as well as the distribution of proliferative cells and
      several calcium-binding proteins (CaBP). The results reveal that the SV begins to
      differentiate on hatching, when immature coronet cells are morphologically
      distinguishable. Further morphogenesis involves the formation of a tubular
      avascular SV, which remains until premetamorphic larval stages. Folding and
      vascularization of the SV occurs mostly during metamorphosis, when S. maximus
      settle down on the bottom. Proliferative cells were placed within the SV itself
      and in the neighbouring infundibular hypothalamus. Their putative relationship
      with the growth of the SV is discussed. The CaBPs analysed are expressed in
      coronet cells. Parvalbumin is expressed in these cells from the beginning of
      their differentiation, while calretinin expression arises in the tubular SV and
      becomes more widespread over time. These data emphasize the importance of calcium
      buffering in the function of coronet cells. 

PMID- 25973993
TI  - Urine Collection Method for the Diagnosis of Congenital Cytomegalovirus
      Infection.
AB  - Congenital cytomegalovirus infection is traditionally diagnosed by virus
      detection in saliva or urine. Virus culture was positive in significantly fewer
      urine samples collected using cotton balls in diapers (55.2%) than with samples
      collected by bags (93.2%) from newborns screened positive for CMV in saliva.
      However, polymerase chain reaction was positive in 95% of urine samples
      regardless of the collection method. 

PMID- 25973994
TI  - The Spectrum of Nocardia Lung Disease in Cystic Fibrosis.
AB  - We reviewed all cases of Nocardia infection in cystic fibrosis patients at 2
      centers. Eight of 200 patients had Nocardia in sputum. Four developed severe lung
      disease, including 3 with associated allergic bronchopulmonary aspergillosis; 4
      remained clinically stable. Nocardia is often associated with significant lung
      disease in cystic fibrosis, possibly associated with allergic bronchopulmonary
      aspergillosis or steroids. 

PMID- 25973995
TI  - Nodular Lung Lesions in a 10-Week-Old Infant.

PMID- 25973996
TI  - Dental caries and tooth loss in adults in the United States, 2011-2012.
AB  - KEY FINDINGS: Among adults aged 20-64, 91% had dental caries and 27% had
      untreated tooth decay. Untreated tooth decay was higher for Hispanic (36%) and
      non-Hispanic black (42%) adults compared with non-Hispanic white (22%) and non
      Hispanic Asian (17%) adults aged 20-64. Adults aged 20-39 were twice as likely to
      have all their teeth (67%) compared with those aged 40-64 (34%). About one in
      five adults aged 65 and over had untreated tooth decay. Among adults aged 65 and
      over, complete tooth loss was lower for older Hispanic (15%) and non-Hispanic
      white (17%) adults compared with older non-Hispanic black adults (29%).

PMID- 25973997
TI  - Trends in elevated triglyceride in adults: United States, 2001-2012.
AB  - KEY FINDINGS: The percentage of adults aged 20 and over with elevated
      triglyceride (150 mg/dL or more) declined from 33.3% during 2001-2004 to 25.1%
      during 2009-2012. Percentages with elevated triglyceride decreased for both men
      and women-among men, from 37.3% for 2001-2004 to 28.7% for 2009-2012, and among
      women, from 29.3% for 2001-2004 to 21.5% for 2009-2012. For adults aged 60 and
      over, declines in elevated triglyceride levels were seen in both men (from 39.9%
      during 2001-2004 to 24.8% during 2009-2012) and women (from 43.5% during 2001
      2004 to 30.9% during 2009-2012). Declines in elevated triglyceride levels were
      observed in overweight and obese men and women between 2001-2004 and 2009-2012.

PMID- 25973998
TI  - Deaths from unintentional injury among adults aged 65 and over: United States,
      2000-2013.
AB  - KEY FINDINGS: In 2012-2013, 55% of all unintentional injury deaths among adults
      aged 65 and over were due to falls. From 2000 through 2013, the age-adjusted fall
      injury death rate among adults aged 65 and over nearly doubled from 29.6 per
      100,000 to 56.7 per 100,000. In 2012-2013, the death rate due to suffocation was
      more than 8 times higher among adults aged 85 and over (26.5 per 100,000)
      compared with adults aged 65-74 (3.1 per 100,000). Among adults aged 65 and over,
      the death rate due to fire was more than twice as high for non-Hispanic black
      adults as for non-Hispanic white and Hispanic adults. The death rate from motor
      vehicle traffic crashes among adults aged 65 and over was 1.7 times higher in
      nonmetropolitan areas compared with metropolitan areas.

PMID- 25973999
TI  - When are babies born: morning, noon, or night? Birth certificate data for 2013.
AB  - KEY FINDINGS: The highest percentages of births occurred during the morning and
      midday hours. Births on Saturday and Sunday were more likely to occur in the late
      evening and early morning hours than births Monday through Friday. Compared with
      induced vaginal deliveries and noninduced vaginal deliveries, cesarean deliveries
      were the least likely to occur during the evening and early morning. Noninduced
      vaginal births were more likely than cesarean and induced vaginal births to occur
      in the early morning. Cesarean deliveries with no trial of labor were much more
      concentrated during the day than were cesarean deliveries with a trial of labor.
      Births delivered in hospitals and all births show similar time-of-day patterns.

PMID- 25974000
TI  - Association between diagnosed ADHD and selected characteristics among children
      aged 4-17 years: United States, 2011-2013.
AB  - KEY FINDINGS: In 2011-2013, 9.5% of children aged 4-17 years were ever diagnosed
      with attention deficit hyperactivity disorder (ADHD). For those aged 4-5,
      prevalence was 2.7%, 9.5% for those aged 6-11, and 11.8% for those aged 12-17.
      Among all age groups, prevalence of ever diagnosed ADHD was more than twice as
      high in boys as girls. Among those aged 6-17, prevalence was highest among non
      Hispanic white children and lowest among Hispanic children. Among all age groups,
      prevalence was higher among children with public insurance compared with children
      with private insurance. Among children aged 4-11, prevalence was higher for
      children with family income less than 200% of the federal poverty threshold than
      for children with family income at 200% or more of the poverty threshold.

PMID- 25974001
TI  - Effects of the PPARalpha agonist WY-14,643 on plasma lipids, enzymatic activities
      and mRNA expression of lipid metabolism genes in a marine flatfish, Scophthalmus
      maximus.
AB  - Fibrates and other lipid regulator drugs are widespread in the aquatic
      environment including estuaries and coastal zones, but little is known on their
      chronic effects on non-target organisms as marine fish. In the present study,
      turbot juveniles were exposed to the PPARalpha model agonist WY-14,643 for 21
      days by repeated injections at the concentrations of 5mg/kg (lo-WY) and 50mg/kg
      (hi-WY), and samples taken after 7 and 21 days. Enzyme activity and mRNA
      expression of palmitoyl-CoA oxidase and catalase in the liver were analyzed as
      first response, which validated the experiment by demonstrating interactions with
      the peroxisomal fatty acid oxidation and oxidative stress pathways in the hi-WY
      treatment. In order to get mechanistic insights, alterations of plasma lipids
      (free cholesterol, FC; HDL associated cholesterol, C-HDL; triglycerides, TG; non
      esterified fatty acids, NEFA) and hepatic mRNA expression of 17 genes involved in
      fatty acid and lipid metabolism were studied. The exposure to hi-WY reduced the
      quantity of plasma FC, C-HDL, and NEFA. Microsomal triglyceride transfer protein
      and apolipoprotein E mRNA expression were higher in hi-WY, and indicated an
      increased formation of VLDL particles and energy mobilization from liver. It is
      speculated that energy depletion by PPARalpha agonists may contribute to a higher
      susceptibility to environmental stressors. 

PMID- 25974002
TI  - Anatomical variations: How do surgical and radiology training programs teach and
      assess them in their training curricula?
AB  - Sound knowledge of anatomy and Anatomical variations plays an integral role in
      surgical and radiology specialties. This study investigated the current teaching
      and assessment trends on Anatomical variations in various surgical and radiology
      specialty training curricula in Canada and Australia. A survey was sent to 122
      Program Directors and Chairs of specialty committees in Canada and Directors of
      Training/Education in Australia of selected surgical and radiology specialties. A
      total of 80.7% of respondents report that their training curricula include
      Anatomical variations. The highest rated classes of variations included in the
      curriculum are arterial (76%), venous (68%), followed by organs (64%). All
      trainees learn about Anatomical variations from surgeons and radiologists (100%)
      and via suggested textbooks of the specialty (87.1%). A total of 54.8% report
      that specialty training curricula do not suggest specific anatomical variation
      classifications for the trainees to learn, and 16.1% are uncertain if the
      colleges provide such kind of instruction. Trainees typically communicated
      findings of variations in case presentations and clinic's meetings. About 32.3%
      of respondents report that Anatomical variations are not assessed in their
      training curriculum. About 39.3% of experienced clinicians in the study report
      they encounter variations on a monthly basis and 25 and 21.4% on a weekly and
      daily basis, respectively. Surgical and radiology colleges need to investigate
      for hidden curriculum in their specialty training programs to ensure there are no
      gaps in knowledge and training related to Anatomical variations. Most educational
      leaders surveyed believe more teaching on Anatomical variations in the first 4
      years of training would benefit resident doctors.

PMID- 25974004
TI  - The challenges of implementing the 2007 UK guidelines for paediatric urinary
      tract infection.

PMID- 25974005
TI  - How the association between mental health and obesity in children can be examined
      in a long-term setting.

PMID- 25974006
TI  - Effect of pioglitazone medication on the incidence of dementia.
AB  - OBJECTIVE: Peroxisome proliferator activated receptor gamma-activating drugs show
      various salutary effects in preclinical models of neurodegenerative disease. The
      decade-long clinical usage of these drugs as antidiabetics now allows for
      evaluation of patient-oriented data sources. METHODS: Using observational data
      from 2004-2010, we analyzed the association of pioglitazone and incidence of
      dementia in a prospective cohort study of 145,928 subjects aged >=60 years who,
      at baseline, were free of dementia and insulin-dependent diabetes mellitus. We
      distinguished between nondiabetics, diabetics without pioglitazone, diabetics
      with prescriptions of <8 calendar quarters of pioglitazone, and diabetics with
      >=8 quarters. Cox proportional hazard models explored the relative risk (RR) of
      dementia incidence dependent on pioglitazone use adjusted for sex, age, use of
      rosiglitazone or metformin, and cardiovascular comorbidities. RESULTS: Long-term
      use of pioglitazone was associated with a lower dementia incidence. Relative to
      nondiabetics, the cumulative long-term use of pioglitazone reduced the dementia
      risk by 47% (RR = 0.53, p = 0.029). If diabetes patients used pioglitazone <8
      quarters, the dementia risk was comparable to those of nondiabetics (RR = 1.16, p
      = 0.317), and diabetes patients without a pioglitazone treatment had a 23%
      increase in dementia risk (RR = 1.23, p < 0.001). We did not find evidence for
      age effects, nor for selection into pioglitazone treatment due to obesity.
      INTERPRETATION: These findings indicate that pioglitazone treatment is associated
      with a reduced dementia risk in initially non-insulin-dependent diabetes mellitus
      patients. Prospective clinical trials are needed to evaluate a possible
      neuroprotective effect in these patients in an ageing population.

PMID- 25974007
TI  - Hepatoprotective activity of Peganum harmala against ethanol-induced liver
      damages in rats.
AB  - In this study, we investigated the protective effects of Peganum harmala seeds
      extract (CPH) against chronic ethanol treatment. Hepatotoxicity was induced in
      male Wistar rats by administrating ethanol 35% (4 g/kg/day) for 6 weeks. CPH was
      co-administered with ethanol, by intraperitonial (IP) injection, at a dose of 10
      mg/kg bw/day. Control rats were injected by saline solution (NaCl 90/00). Chronic
      ethanol administration intensified lipid peroxidation monitored by an increase of
      TBARS level in liver. Ethanol treatment caused also a drastic alteration in
      antioxidant defence system; hepatic superoxide dismutase (SOD), catalase (CAT)
      and glutathione peroxidase (GPx) activities. A co-administration of CPH during
      ethanol treatment inhibited lipid peroxidation and improved antioxidants
      activities. However, treatment with P. harmala extract protects efficiently the
      hepatic function of alcoholic rats by the considerable decrease of
      aminotransferase contents in serum of ethanol-treated rats. 

PMID- 25974008
TI  - The effects of bronchodilator drugs and antibiotics used for respiratory
      infection on human erythrocyte carbonic anhydrase I and II isozymes.
AB  - Carbonic anhydrase (CA) is an enzyme which plays role/roles in various
      homeostatic mechanisms, such as the acid-base balance and electrolyte secretion
      in various tissues. This study aimed to determine and to compare possible
      alterations in activity of this enzyme caused by use of bronchodilator drugs and
      respiratory infection antibiotics. CA I and II were purified from human
      erythrocytes by a simple one step procedure using Sepharose 4B-L-tyrosine
      sulfonamide affinity column. The iso-enzymes were purified 259.16-fold with a
      yield of 31.74%. CAI and II isozymes were treated with several drugs, then the
      inhibition or activation of the enzymes were determined. The results of this
      study show that itrapropium bromide is the most effective inhibitor for human
      erythrocytes carbonic anhydrase compared with the other bronchodilator drugs. 

PMID- 25974009
TI  - Electronic properties of environmental pollutants and their mutagenic activity:
      Nitro derivatives of azaphenanthrenes.
AB  - The physico-chemical properties of nitroazaphenanthrene isomers: 4-nitro-9
      azaphenanthrene (4-N-9-Aph), 5-nitro-9-azaphenanthrene (5-N-9-Aph), 6-nitro-4
      azaphenanthrene (6-N-4-Aph), 8-nitro-1-azaphenanthrene (8-N-1-Aph), and 8-nitro-4
      azaphenanthrene (8-N-4-Aph) have been investigated theoretically using Density
      Functional Theory (DFT) calculations. Equilibrium geometries, relative stability,
      ionization potentials, electron affinities, molecular electrostatic potentials,
      dipole moments, electric polarizabilities, and vibrational properties of these
      isomers are presented. Averaged O-N-C-C dihedral angle, dipole moment,
      polarizability, the summation of IR intensities (?IIR) and the summation of Raman
      activities (?ARaman) over all 3N-6 vibrational degrees of freedom are sensitive
      to the structure of isomers. A very good linear relationship between ?ARaman
      values (R=1.00) and the Salmonella typhimurium strain TA98(-S9) mutagenic
      activity of the investigated nitroazaphenanthrene isomers (Tokiwa et al., 2003)
      reveals a very important role of inductive and dispersive forces on the mutagenic
      pathways of the investigated isomers. 

PMID- 25974010
TI  - Computational study of binding affinity to nuclear receptors for some cosmetic
      ingredients.
AB  - We studied the ingredients of cosmetic products as potential endocrine disruptors
      (ED) by in silico methods (docking). The structures of 14 human nuclear receptors
      have been retrieved from the protein data bank (PDB). We only considered the
      mechanism linked with direct binding to nuclear receptors with well-defined
      crystal structures. Predictions were performed using the Endocrine Disruptome
      docking program http://endocrinedisruptome.ki.si/ (Kolsek et al., 2013). 122
      compounds were estimated to be possible endocrine disruptors bind to at least one
      of the receptors, 21 of them which are predicted to be probable toxicants for
      endocrine disruption as they bind to more than five receptors simultaneously.
      According to the literature survey and lack of experimental data it remains a
      challenge to prove or disprove the in silico results experimentally also for
      other potential endocrine disruptors. 

PMID- 25974011
TI  - Risk Factors for Postoperative Retention After Hemorrhoidectomy: A Cohort Study.
AB  - The objective of this study was to identify the risk factors for urinary
      retention after hemorrhoidectomy. With the approval of West China Hospital of
      Sichuan University Ethics Board, data were abstracted from 961 charts of patients
      who underwent hemorrhoidectomy from January 1, 2009, to June 30, 2011. The
      outcome was urinary retention in the first 24 hours after surgery. Risk factors
      were identified using multivariable logistic regression, and they were expressed
      as odds ratios or 95% confidence intervals. The overall urinary retention rate
      was 14.8% (n = 142). Significant risk factors associated with postoperative
      urinary retention included female gender, anesthesia methods, severity of
      hemorrhoid, a large amount of intravenous fluid administered perioperatively, and
      length of hospital stay. Logistic regression analysis revealed that female gender
      (odds ratio, 2.607; p < .01), sacral anesthesia (odds ratio, 2.481; p = .02),
      more than 3 hemorrhoids resected (odds ratio, 2.658; p < .01), hemorrhoids having
      4 degrees of severity (odds ratio, 3.101; p < .01), intravenous fluids > 700 ml
      (odds ratio, 1.597; p = .02), and length of stay more than 7 days (odds ratio,
      1.852; p < .01) were significant predictors of urinary retention post
      hemorrhoidectomy.

PMID- 25974012
TI  - CONSIDERATION OF ACETYLCHOLINE ANTAGONISTS FOR NAUSEA AND VOMITING.

PMID- 25974013
TI  - Focus on the London Dielectrophoresis 2014 meeting.

PMID- 25974018
TI  - Evaluation of a new cryptococcal antigen lateral flow immunoassay in serum,
      cerebrospinal fluid and urine for the diagnosis of cryptococcosis: a meta
      analysis and systematic review.
AB  - BACKGROUND: A new lateral flow immunoassay (LFA) for the detection of
      cryptococcal antigen was developed. OBJECTIVE: We aimed to systematically review
      all relevant studies to evaluate the diagnostic accuracy of the cryptococcal
      antigen LFA on serum, CSF and urine specimens. METHODS: We searched public
      databases including PubMed, Web of Science, Elsevier Science Direct and Cochrane
      Library for the English-language literature published up to September 2014. We
      conducted meta-analyses of sensitivity, specificity, positive likelihood ratio
      (PLR), negative likelihood ratio (NLR) and diagnostic odds ratios (DOR) and SROC
      of LFA in serum and CSF, respectively. The sensitivity of LFA in urine was also
      analyzed. Subgroup analyses were carried out to analyze the potential
      heterogeneity. RESULTS: 12 studies were included in this study. The pooled
      sensitivity and specificity values of LFA in serum were 97.6% (95% CI, 95.6% to
      98.9%) and 98.1% (95% CI, 97.4% to 98.6%), respectively. The average PLR of LFA
      in serum was 43.787 (95% CI, 22.60-84.81) and the NLR was 0.03 (95% CI, 0.01
      0.09). The pooled DOR was 2180.30 (95% CI, 868.92-5471.00) and the AUC was
      0.9968. The pooled sensitivity and specificity values of LFA in CSF were 98.9%
      (95% CI, 97.9% to 99.5%) and 98.9% (95% CI, 98.0% to 99.5%), respectively. The
      average PLR of LFA in serum was 48.83 (95% CI, 21.59-110.40) and the NLR was 0.02
      (95% CI, 0.01-0.04). The pooled DOR was 2931.10 (95% CI, 1149.20-7475.90) and the
      AUC was 0.9974. The pooled sensitivity value of LFA in urine was 85.0% (95% CI,
      78.7% to 90.1%). CONCLUSIONS: The study demonstrates a very high accuracy of LFA
      in serum and CSF for the diagnosis of cryptococcosis in patients at risk. LFA in
      urine can be a promising sample screening tool for early diagnosis of
      cryptococcosis.

PMID- 25974020
TI  - Use of Aprepitant and Factors Associated With Incidence of Postoperative Nausea
      and Vomiting in Patients Undergoing Facial Plastic Surgery.
AB  - IMPORTANCE: Patients who experience immediate postoperative nausea and vomiting
      (PONV) after their facial plastic surgery procedure have a higher incidence of
      complications and dissatisfaction. OBJECTIVES: To determine whether a single dose
      of aprepitant administered preoperatively can decrease the incidence of immediate
      PONV in patients undergoing facial plastic surgery compared with patients who are
      administered ondansetron hydrochloride alone and whether patient-related factors
      pose a greater risk of developing immediate PONV after surgery. DESIGN, SETTING,
      AND PARTICIPANTS: In this retrospective study, we reviewed 172 patients
      undergoing facial plastic surgery with general anesthesia at an accredited office
      based surgery practice from January 1, 2012, through December 31, 2013.
      INTERVENTIONS: All patients received prophylactic treatment to mitigate against
      immediate PONV. Fifty-six patients received aprepitant in addition to ondansetron
      as prophylaxis for PONV. MAIN OUTCOMES AND MEASURES: Patients undergoing facial
      plastic surgery were assessed during the immediate postoperative period for PONV.
      In addition, patient age, type of procedure, duration of surgery, and sex were
      reported. RESULTS: The addition of aprepitant preoperatively effectively reduced
      the PONV rate from 15.5% to 1.8% (P = . 02). Logistic regression analysis
      revealed that duration of surgery longer than 90 minutes (odds ratio [OR], 2.936;
      95% CI, 0.560-15.385; P = .20), female sex (OR, 1.893; 95% CI, 0.379-9.448; P =
      .44), and type of procedure increased the likelihood of PONV after facial plastic
      surgery with an odds ratio of greater than 1 in this sample population. However,
      the odds ratios were not statistically significantly greater than 1 for the 95%
      CIs. Of the 19 patients who experienced PONV, 17 were women, and 17 patients had
      a duration of surgery longer than 90 minutes. Patient age did not appear to
      affect the rate of PONV (P = .32). CONCLUSIONS AND RELEVANCE: Preoperative
      aprepitant administered within 1 hour before facial plastic surgery in patients
      at risk of developing PONV effectively reduce the rate of immediate PONV. Female
      patients and patients with facial surgery duration of longer than 90 minutes
      might benefit from the added expense of aprepitant to further reduce the
      likelihood of PONV. LEVEL OF EVIDENCE: 3.

PMID- 25974019
TI  - Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the
      Skin by CD4+ T Cells That Are Functionally Suppressive.
AB  - The skin provides an important first line of defence and immunological barrier to
      invasive pathogens, but immune responses must also be regulated to maintain
      barrier function and ensure tolerance of skin surface commensal organisms. In
      schistosomiasis-endemic regions, populations can experience repeated percutaneous
      exposure to schistosome larvae, however little is known about how repeated
      exposure to pathogens affects immune regulation in the skin. Here, using a murine
      model of repeated infection with Schistosoma mansoni larvae, we show that the
      skin infection site becomes rich in regulatory IL-10, whilst in its absence,
      inflammation, neutrophil recruitment, and local lymphocyte proliferation is
      increased. Whilst CD4+ T cells are the primary cellular source of regulatory IL
      10, they expressed none of the markers conventionally associated with T
      regulatory (Treg) cells (i.e. FoxP3, Helios, Nrp1, CD223, or CD49b).
      Nevertheless, these IL-10+ CD4+ T cells in the skin from repeatedly infected mice
      are functionally suppressive as they reduced proliferation of responsive CD4+ T
      cells from the skin draining lymph node. Moreover, the skin of infected Rag-/-
      mice had impaired IL-10 production and increased neutrophil recruitment. Finally,
      we show that the mechanism behind IL-10 production by CD4+ T cells in the skin is
      due to a combination of an initial (day 1) response specific to skin commensal
      bacteria, and then over the following days schistosome-specific CD4+ T cell
      responses, which together contribute towards limiting inflammation and tissue
      damage following schistosome infection. We propose CD4+ T cells in the skin that
      do not express markers of conventional T regulatory cell populations have a
      significant role in immune regulation after repeated pathogen exposure and
      speculate that these cells may also help to maintain skin barrier function in the
      context of repeated percutaneous insult by other skin pathogens. 

PMID- 25974021
TI  - Identical MicroRNAs Regulate Liver Protection during Anaesthetic and Ischemic
      Preconditioning in Rats: An animal study.
AB  - Anaesthetic preconditioning (APC) and ischemic preconditioning (IPC) ameliorate
      liver ischemia-reperfusion (I/R) injury and are important for regulating hepatic
      I/R injury. MicroRNAs (miRNAs) are short, noncoding RNA molecules of 21-23
      nucleotides in length, and are currently under intensive investigation regarding
      their ability to regulate gene expression in a wide range of species. miRNA
      activity is involved in controlling a wide range of biological functions and
      processes. We evaluated whether APC and IPC are mediated by the same miRNAs by
      performing comprehensive miRNA screening experiments in a rat model of hepatic
      I/R injury. Twenty-one rats were randomly divided into three groups (n =
      7/group): control (mock preconditioning), APC, and IPC. Control rats were
      subjected to 60 min of hepatic ischemia followed by 4 h of reperfusion, whereas
      the APC and IPC groups were preconditioned with 2% sevoflurane and hepatic
      ischemia for 10 min prior to ischemia-reperfusion, respectively. Liver samples
      were collected to measure miRNA levels after 3 h of reperfusion, and gene
      networks and canonical pathways were identified using Ingenuity Pathway Analysis
      (IPA). Blood samples were collected to measure the levels of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT). Although haemodynamic
      parameters did not vary among the groups, AST and ALT levels were significantly
      higher in the control group than in the APC and IPC groups. Comprehensive miRNA
      screening experiments revealed that most miRNAs altered in the APC group were
      common to those in the IPC group. IPA identified five miRNAs related to the Akt
      glycogen synthase kinase-3beta (GSK-3beta)-cyclin D1 pathway that were
      significantly affected by both preconditioning strategies. The application of
      either APC or IPC to ameliorate hepatic I/R injury results in expression of
      several common miRNAs that are related to the Akt-GSK-cyclin D1 pathway. 

PMID- 25974022
TI  - Efficacy of Acupuncture for Bell's Palsy: A Systematic Review and Meta-Analysis
      of Randomized Controlled Trials.
AB  - Acupuncture has emerged as an alternative therapy for Bell's palsy in both adults
      and children. However, the use of acupuncture is controversial. We conducted a
      systematic review and meta-analysis to assess the efficacy of acupuncture for
      Bell's palsy. We searched PubMed, Embase, and the Cochrane Central Register of
      Controlled Trials, irrespective of any language restrictions. Randomized
      controlled trials comparing acupuncture with other therapies for Bell's palsy in
      adults or children were included. Fourteen randomized controlled trials involving
      1541 individuals were included in this meta-analysis. Significant association was
      observed in acupuncture with a higher effective response rate for Bell's palsy
      (relative risk, 1.14; 95% confidence interval, 1.04-1.25; P = 0.005) but there
      was a heterogeneity among the studies (I2 = 87%). An assessment of the included
      studies revealed a high risk of bias in methodological quality. An evaluation of
      the incidence of complications was not available, owing to incomplete data.
      Acupuncture seems to be an effective therapy for Bell's palsy, but there was
      insufficient evidence to support the efficacy and safety of acupuncture. However,
      the results should be interpreted cautiously, because of the poor quality and
      heterogeneity of the included studies. 

PMID- 25974023
TI  - The association of systemic oxidative stress with insulin resistance: mechanistic
      insights from studies in Bartter's and Gitelman's syndromes.

PMID- 25974025
TI  - Optogenetics and the circuit dynamics of psychiatric disease.

PMID- 25974026
TI  - New insights in the treatment of radioiodine refractory differentiated thyroid
      carcinomas: to lenvatinib and beyond.
AB  - During the past two decades, several key somatic mutations associated with
      development and progression of differentiated thyroid cancer (DTC) have been
      revealed. Historically, the treatment for advanced DTC is challenging after
      patients become refractory to radioactive iodine. The response to doxorubicin,
      the only chemotherapy agent approved by the US Food and Drug Administration, is
      disappointing either as monotherapy or combination therapy. Because of the lack
      of effective systemic treatment coupled with increased understanding of molecular
      and cellular pathogenesis, multiple kinase inhibitors (MKIs) as an alternative
      therapy for the treatment of advanced DTC has generated much interest,
      enthusiasm, and, most excitingly, promising results. After the encouraging
      results of these agents in earlier trials, the Food and Drug Administration
      approved sorafenib for the treatment of locally recurrent, progressive, or
      metastatic DTC refractory to radioactive iodine treatment based on the results of
      a multicenter DECISION trial. Sorafenib therefore became the first MKI approved
      for this indication in more than 20 years. However, even more impressive
      responses and progression-free survival benefits were seen in the phase III
      SELECT trial with lenvatinib, giving even higher hopes for the future management
      of what was considered just a decade ago an orphan disease. Given the role of
      MKIs, a new era in the treatment of advanced DTC has begun. We review the key
      therapeutic targets, oncogenic pathways, and promising clinical results of these
      agents in refractory disease, as well as their roles after failure of first line
      kinase inhibitors. 

PMID- 25974024
TI  - Conformation-activity relationships of polyketide natural products.
AB  - Polyketides represent an important class of secondary metabolites that interact
      with biological targets connected to a variety of disease-associated pathways.
      Remarkably, nature's assembly lines, polyketide synthases, manufacture these
      privileged structures through a combinatorial mixture of just a few structural
      units. This review highlights the role of these structural elements in shaping a
      polyketide's conformational preferences, the use of computer-based molecular
      modeling and solution NMR studies in the identification of low-energy conformers,
      and the importance of conformational analogues in probing the bound conformation.
      In particular, this review covers several examples wherein conformational
      analysis complements classic structure-activity relationships in the design of
      biologically active natural product analogues.

PMID- 25974027
TI  - AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells.
AB  - Human cutaneous melanoma is an aggressive and chemotherapy-resistant type of
      cancer. AM251 is a cannabinoid type 1 (CB1) receptor antagonist/inverse agonist
      with off-target antitumor activity against pancreatic and colon cancer cells. The
      current study aimed to characterize the in-vitro antimelanoma activity of AM251.
      The BRAF V600E mutant melanoma cell line, A375, was used as an in-vitro model
      system. Characterization tools included a cell viability assay, nuclear
      morphology assessment, gene expression, western blot, flow cytometry with Annexin
      V-FITC/7-AAD double staining, cell cycle analyses, and measurements of changes in
      intracellular cAMP and calcium concentrations. AM251 exerted a marked cytotoxic
      effect against A375 human melanoma cells with potency comparable with that
      observed for cisplatin without significant changes in the human dermal
      fibroblasts viability. AM251, at a concentration that approximates the IC50,
      downregulated genes encoding antiapoptotic proteins (BCL2 and survivin) and
      increased transcription levels of proapoptotic BAX, induced alteration of Annexin
      V reactivity, DNA fragmentation, chromatin condensation in the cell nuclei, and
      G2/M phase arrest.AM251 also induced a 40% increase in the basal cAMP levels, but
      it did not affect intracellular calcium concentrations. The involvement of GPR55,
      TRPA1, and COX-2 in the AM251 mechanism of action was excluded. The combination
      of AM251 with celecoxib produced a synergistic antitumor activity, although the
      mechanism underlying this effect remains to be elucidated. This study provides
      the first evidence of a proapoptotic effect and G2/M cell cycle arrest of AM251
      on A375 cells. This compound may be a potential prototype for the development of
      promising diarylpyrazole derivatives to be evaluated in human cutaneous melanoma.

PMID- 25974028
TI  - A new gender-specific model for skin autofluorescence risk stratification.
AB  - Advanced glycation endproducts (AGEs) are believed to play a significant role in
      the pathophysiology of a variety of diseases including diabetes and
      cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement
      serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and
      skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the
      existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD
      = 0.57) arbitrary units (AU), which is considerably higher than the values
      reported for other populations. We show a previously unreported and significant
      difference in SAF values between men and women, with median (range) values of
      1.77 AU (0.79-4.84 AU) and 2.20 AU (0.75-4.59 AU) respectively (p-value " 0.01).
      Age, presence of diabetes and BMI were the most influential variables in
      determining SAF values in men, whilst in female participants, SR was also highly
      correlated with SAF. Diabetes, hypertension and obesity all showed strong
      association with SAF, particularly when gender differences were taken into
      account. We propose an adjusted, gender-specific disease risk stratification
      scheme for Middle Eastern populations. SAF is a potentially valuable clinical
      screening tool for cardiovascular risk assessment but risk scores should take
      gender and ethnicity into consideration for accurate diagnosis. 

PMID- 25974030
TI  - Improved glucose control with reduced hypoglycaemic risk when linagliptin is
      added to basal insulin in elderly patients with type 2 diabetes.
AB  - AIM: To assess the efficacy, hypoglycaemia risk and other safety markers of
      linagliptin as an additional therapy in older patients (aged >=70 years)
      inadequately controlled with basal insulin. METHODS: A prespecified safety
      analysis from the linagliptin trials programme was carried out to explore the
      hypoglycaemia risk when linagliptin was added to background basal insulin therapy
      in elderly patients (>=70 years). To do this, two eligible, randomized, placebo
      controlled, clinical trials (NCT00954447 and NCT01084005) of 24 and >=52 weeks,
      respectively, were analysed. RESULTS: A total of 247 elderly individuals [mean +/
      standard deviation (s.d.) age 74 +/- 4 years, glycated haemoglobin (HbA1c) 8.2
      +/- 0.8%] on basal insulin (mean +/- s.d. baseline dose 36 +/- 25 IU/day) were
      identified. Alongside placebo-adjusted change in HbA1c with linagliptin of -0.77%
      [95% confidence interval (CI) -0.95 to 0.59; p < 0.0001] after 24 weeks, the
      hazard ratios (HRs) of both overall and confirmed hypoglycaemia [blood glucose
      <=3.9 mmol/l (70 mg/dl)], were significantly lower with linagliptin than with
      placebo: HR 0.61 (95% CI 0.39-0.97) versus 0.59 (95% CI 0.37-0.94), respectively
      (both p < 0.05). Moreover, significantly less confirmed hypoglycaemia was present
      in linagliptin-treated patients with renal impairment [HR 0.45 (95% CI 0.27
      0.76)], moderate hyperglycaemia [HbA1c 7.5 to <9.0%; HR 0.51 (95% CI 0.27-0.99)],
      lower fasting plasma glucose levels [<152 mg/dl; HR 0.49 (95% CI 0.28-0.86)] and
      those treated with higher insulin doses [insulin >=35.6 IU/day; HR 0.46 (95% CI
      0.23-0.91); p < 0.05 for all]. Severe hypoglycaemia was rare and the incidence
      was lower with linagliptin (0.8%) versus placebo (2.5%): HR 0.21 (95% CI 0.02
      2.30). CONCLUSIONS: Despite improvements in hyperglycaemia and no relevant on
      trial insulin dose reductions, adding linagliptin to basal insulin appears to
      decrease hypoglycaemia risk. The biological basis of this phenomenon warrants
      further research but may involve counter-regulatory effects of incretin hormones.

PMID- 25974029
TI  - Co-evolution of somatic variation in primary and metastatic colorectal cancer may
      expand biopsy indications in the molecular era.
AB  - INTRODUCTION: Metastasis is thought to be a clonal event whereby a single cell
      initiates the development of a new tumor at a distant site. However the degree to
      which primary and metastatic tumors differ on a molecular level remains unclear.
      To further evaluate these concepts, we used next generation sequencing (NGS) to
      assess the molecular composition of paired primary and metastatic colorectal
      cancer tissue specimens. METHODS: 468 colorectal tumor samples from a large
      personalized medicine initiative were assessed by targeted gene sequencing of
      1,321 individual genes. Eighteen patients produced genomic profiles for 17 paired
      primary:metastatic (and 2 metastatic:metastatic) specimens. RESULTS: An average
      of 33.3 mutations/tumor were concordant (shared) between matched samples,
      including common well-known genes (APC, KRAS, TP53). An average of 2.3
      mutations/tumor were discordant (unshared) among paired sites. KRAS mutational
      status was always concordant. The overall concordance rate for mutations was
      93.5%; however, nearly all (18/19 (94.7%)) paired tumors showed at least one
      mutational discordance. Mutations were seen in: TTN, the largest gene (5
      discordant pairs), ADAMTS20, APC, MACF1, RASA1, TP53, and WNT2 (2 discordant
      pairs), SMAD2, SMAD3, SMAD4, FBXW7, and 66 others (1 discordant pair).
      CONCLUSIONS: Whereas primary and metastatic tumors displayed little variance
      overall, co-evolution produced incremental mutations in both. These results
      suggest that while biopsy of the primary tumor alone is likely sufficient in the
      chemotherapy-naive patient, additional biopsies of primary or metastatic disease
      may be necessary to precisely tailor therapy following chemotherapy resistance or
      insensitivity in order to adequately account for tumor evolution.

PMID- 25974031
TI  - RF instrumentation for same-breath triple nuclear lung MR imaging of (1)H and
      hyperpolarized (3)He and (129)Xe at 1.5T.
AB  - PURPOSE: The hyperpolarized gases (3)He and (129)Xe have distinct properties and
      provide unique and complementary functional information from the lungs. A triple
      nuclear, same-breath imaging examination of the lungs with (1)H, (3)He, and
      (129)Xe can therefore provide exclusive functional information from the gas
      images. In addition, the (1)H images provide complementary co-registered
      structural information in the same physiological time frame. The goal of this
      study was to design an RF system for triple nuclear lung MRI at 1.5T, consisting
      of a dual-tuned transceiver coil for (3)He and (129)Xe, RF switches and a nested
      (1)H receiver array. METHODS: A dual-tuned transmit-receive dual-Helmholtz RF
      coil for (3)He and (129)Xe was designed and constructed to work in unison with a
      nested (1)H receiver array. RESULTS: Triple-nuclear imaging (structural and
      ventilation) and apparent diffusion coefficient mapping of the human lungs was
      performed in the same breath-hold using the integrated RF system. B1 maps and
      volumetric ventilation imaging using a three-dimensional, balanced steady-state
      free precession pulse sequence performed with both hyperpolarized (3)He and
      (129)Xe indicate good stand-alone performance of the coil for the respective
      nucleus. CONCLUSION: Triple-nuclear same-breath lung imaging with a dual-tuned
      coil ((3)He and (129)Xe) and a nested (1)H array has been demonstrated with a
      custom RF system.

PMID- 25974032
TI  - Supramolecular Assembly and Coalescence of Ferritin Cages Driven by Designed
      Protein-Protein Interactions.
AB  - A genetically encoded system for expression of supramolecular protein assemblies
      (SMPAs) based on a fusion construct between ferritin and citrine (YFP) was
      transferred from a mammalian to a bacterial host. The assembly process is
      revealed to be independent of the expression host, while dimensions and level of
      order of the assembled structures were influenced by the host organism. An
      additional level of interactions, namely, coalescence between the preformed
      SMPAs, was observed during the purification process. SAXS investigation revealed
      that upon coalescence, the local order of the individual SMPAs was preserved.
      Finally, the chaotropic agent urea effectively disrupted both the macroscopic
      coalescence and the interactions at the nanoscale until the level of the single
      ferritin cage.

PMID- 25974034
TI  - A rapid test (STic Expert(r) ) for the diagnosis of heparin-induced
      thrombocytopenia.

PMID- 25974033
TI  - Congenital anomalies in children exposed to antithyroid drugs in-utero: a meta
      analysis of cohort studies.
AB  - BACKGROUND: Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is
      commonly managed with antithyroid drugs (ATDs). However, previous studies about
      the effects of ATDs on congenital anomalies are controversial. Therefore, the
      present meta-analysis was performed to explore the risk of congenital anomalies
      in children exposed to ATDs in-utero. METHODS: Embase, Pubmed, Web of Knowledge,
      and BIOSIS Citation Index were searched to find out studies about congenital
      anomalies in children exposed to ATDs in-utero reported up to May 2014. The
      references cited by the retrieved articles were also searched. The relative risks
      (RRs) and confidence intervals (CIs) for the individual studies were pooled by
      fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests.
      RESULTS: Eight studies met the inclusion criteria. Exposure to propylthiouracil
      (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in
      7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64
      (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after
      exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively. CONCLUSIONS: The meta
      analysis suggests that exposure to ATDs in-utero increases the risk of congenital
      anomalies. The use of ATDs in pregnancy should be limited when possible. Further
      research is needed to delineate the exact teratogenic risk for particular
      congenital anomaly.

PMID- 25974035
TI  - Partitioning Variability of a Compartmentalized In Vitro Transcriptional
      Thresholding Circuit.
AB  - Encapsulation of in vitro biochemical reaction circuits into small, cell-sized
      compartments can result in considerable variations in the dynamical properties of
      the circuits. As a model system, we here investigate a simple in vitro
      transcriptional reaction circuit, which generates an ultrasensitive fluorescence
      response when the concentration of an RNA transcript reaches a preset threshold.
      The reaction circuit is compartmentalized into spherical water-in-oil
      microemulsion droplets, and the reaction progress is monitored by fluorescence
      microscopy. A quantitative statistical analysis of thousands of individual
      droplets ranging in size from a few up to 20 MUm reveals a strong variability in
      effective RNA production rates, which by computational modeling is traced back to
      a larger-than-Poisson variability in RNAP activities in the droplets. The noise
      level in terms of the noise strength (the Fano factor) is strongly dependent on
      the ratio between transcription templates and polymerases, and increases for
      higher template concentrations. 

PMID- 25974036
TI  - Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via
      the Activation of the Nrf2 Pathway.
AB  - Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the
      long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin
      extract (GSPE) has been reported to possess a broad spectrum of pharmacological
      and therapeutic properties against oxidative stress. However, its protective
      effects against diabetic bladder dysfunction have not been clarified. This study
      focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by
      streptozotocin. After 8 weeks of GSPE administration, the bladder function of the
      diabetic rats was improved significantly, as indicated by both urodynamics
      analysis and histopathological manifestation. Moreover, the disordered activities
      of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were
      partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in
      the bladder caused by DM was decreased following the administration of GSPE
      according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick
      End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of
      apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore,
      GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by
      the increased expression of nerve growth factor (NGF) and decreased expression of
      the precursor of nerve growth factor (proNGF). GSPE also activated nuclear
      erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription
      factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1).
      These findings suggested that GSPE could ameliorate diabetic bladder dysfunction
      and decrease the apoptosis of the bladder in diabetic rats, a finding that may be
      associated with its antioxidant activity and ability to activate the Nrf2 defense
      pathway. 

PMID- 25974037
TI  - From River Blindness to Neglected Tropical Diseases--Lessons Learned in Africa
      for Programme Implementation and Expansion by the Non-governmental Partners.

PMID- 25974038
TI  - Economic implications of cardiovascular disease management programs: moving
      beyond one-off experiments.
AB  - Substantial variation in economic analyses of cardiovascular disease management
      programs hinders not only the proper assessment of cost-effectiveness but also
      the identification of heterogeneity of interest such as patient characteristics.
      The authors discuss the impact of reporting and methodological variation on the
      cost-effectiveness of cardiovascular disease management programs by introducing
      issues that could lead to different policy or clinical decisions, followed by the
      challenges associated with net intervention effects and generalizability. The
      authors conclude with practical suggestions to mitigate the identified issues.
      Improved transparency through standardized reporting practice is the first step
      to advance beyond one-off experiments (limited applicability outside the study
      itself). Transparent reporting is a prerequisite for rigorous cost-effectiveness
      analyses that provide unambiguous implications for practice: what type of program
      works for whom and how. 

PMID- 25974039
TI  - Explaining electrostatic charging and flow of surface-modified acetaminophen
      powders as a function of relative humidity through surface energetics.
AB  - Powder flow involves particle-particle and particle-vessel contacts and
      separation resulting in electrostatic charging. This important phenomenon was
      studied for uncoated and dry-coated micronized acetaminophen (MAPAP) as a
      function of relative humidity. The main hypothesis is that by modifying powder
      surface energy via dry coating of MAPAP performed using magnetically assisted
      impaction coating, its charging tendency, flow can be controlled. The examination
      of the relationship between electrostatic charging, powder flow, and the surface
      energies of the powders revealed that an improvement in flow because of dry
      coating corresponded to a decrease in the charging of the particles. A general
      trend of reduction in both electrostatic charging and dispersive surface energy
      with dry coating and relative humidity were also observed, except that a
      divergent behavior was observed at higher relative humidities (>=55% RH). The
      uncoated powder was found to have strong electron acceptor characteristic as
      compared with the dry coated. The adhesion energy between the particles and the
      tubes used for the electrostatic charging qualitatively predicted the decreasing
      trend in electrostatic charging from plastic tubes to stainless steel. In
      summary, the surface energies of the powders and the vessel could explain the
      electrostatic charging behavior and charge reduction because of dry coating.

PMID- 25974041
TI  - Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3
      Inflammasome in a Rodent Model of Type 2 Diabetes.
AB  - Low-grade chronic inflammation (metaflammation) is a major contributing factor
      for the onset and development of metabolic diseases, such as type 2 diabetes,
      obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present
      in milk and beer, is a functional vitamin B3 having advantageous effects on
      metabolic regulation. However, the anti-inflammatory capacity of NR is unknown.
      This study evaluated whether NR modulates hepatic nucleotide binding and
      oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3)
      inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR
      group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was
      administrated by an osmotic pump for 7 days. Glucose control, lipid profiles,
      NLRP3 inflammasome, and inflammation markers were analyzed, and structural and
      histological analyses were conducted. NR treatment did not affect body weight
      gain, food intake, and liver function. Glucose control based on the oral glucose
      tolerance test and levels of serum insulin and adiponectin was improved by NR
      treatment. Among tested lipid profiles, NR lowered the total cholesterol
      concentration in the liver. Histological and structural analysis by hematoxylin
      and eosin staining and transmission electron microscopy, respectively, showed
      that NR rescued the disrupted cellular integrity of the mitochondria and nucleus
      in the livers of obese and diabetic KK mice. In addition, NR treatment
      significantly improved hepatic proinflammatory markers, including tumor necrosis
      factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied
      by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and
      caspase1). These results demonstrate that NR attenuates hepatic metaflammation by
      modulating the NLRP3 inflammasome. 

PMID- 25974042
TI  - Compost biodegradation of recalcitrant hoof keratin by bacteria and fungi.
AB  - AIMS: Compost activities efficiently break down a wide range of organic
      substances over time. In this study, bovine hoof was used as recalcitrant protein
      model to gain so far cryptic information on biodegradation during livestock
      mortalities composting. METHODS AND RESULTS: Bovine hooves (black and white),
      containing different amounts of melanin, placed into nylon bags were monitored
      during composting of cattle mortalities for up to 230 days. Besides
      physiochemical analysis, bacterial 16S and fungal 18S DNA fragments were
      amplified by PCR and profiles were separated by DGGE. Sequence analysis of
      separated fragments revealed various bacterial and fungal identities during
      composting. The microbial diversity was affected by a time-temperature
      interaction and by the hoof colour. Our molecular data, supported by electron
      microscopy, suggest hoof colonization by shifting bacteria and fungi communities.
      CONCLUSION: During composting, microbial communities work collaboratively in the
      degradation of recalcitrant organic matter such as keratin over time.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A number of biomolecules including
      recalcitrant proteins may persist in environmental reservoirs, but breakdown can
      occur during composting. A combination of bioactivity and physiochemical
      conditions appear to be decisive for the fate of persistent biomolecules.

PMID- 25974043
TI  - Power ultrasound in meat processing.
AB  - Ultrasound has a wide range of applications in various agricultural sectors. In
      food processing, it is considered to be an emerging technology with the potential
      to speed up processes without damaging the quality of foodstuffs. Here we review
      the reports on the applications of ultrasound specifically with a view to its use
      in meat processing. Emphasis is placed on the effects on quality and
      technological properties such as texture, water retention, colour, curing,
      marinating, cooking yield, freezing, thawing and microbial inhibition. After the
      literature review it is concluded that ultrasound is a useful tool for the meat
      industry as it helps in tenderisation, accelerates maturation and mass transfer,
      reduces cooking energy, increases shelf life of meat without affecting other
      quality properties, improves functional properties of emulsified products, eases
      mould cleaning and improves the sterilisation of equipment surfaces. 

PMID- 25974040
TI  - The HSP90 Inhibitor Ganetespib Alleviates Disease Progression and Augments
      Intermittent Cyclophosphamide Therapy in the MRL/lpr Mouse Model of Systemic
      Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex, systemic autoimmune disease with
      a diverse range of immunological and clinical manifestations. The introduction of
      broad spectrum immunosuppressive therapies and better management of acute disease
      exacerbations have improved outcomes for lupus patients over recent years.
      However, these regimens are burdened by substantial toxicities and confer
      significantly higher risks of infection, thus there remains a significant and
      unmet medical need for alternative treatment options, particularly those with
      improved safety profiles. Heat shock protein 90 (HSP90) is a ubiquitously
      expressed molecular chaperone that acts as an important modulator of multiple
      innate and adaptive inflammatory processes. Of note, accumulating clinical and
      experimental evidence has implicated a role for HSP90 in the pathogenesis of SLE.
      Here we evaluated the potential of HSP90 as a therapeutic target for this disease
      using the selective small molecule inhibitor ganetespib in the well-characterized
      MRL/lpr autoimmune mouse model. In both the prophylactic and therapeutic dosing
      settings, ganetespib treatment promoted dramatic symptomatic improvements in
      multiple disease parameters, including suppression of autoantibody production and
      the preservation of renal tissue integrity and function. In addition, ganetespib
      exerted profound inhibitory effects on disease-related lymphadenopathy and
      splenomegaly, and reduced pathogenic T and B cell lineage populations in the
      spleen. Ganetespib monotherapy was found to be equally efficacious and tolerable
      when compared to an effective weekly dosing regimen of the standard-of-care
      immunosuppressive agent cyclophosphamide. Importantly, co-treatment of ganetespib
      with a sub-optimal, intermittent dosing schedule of cyclophosphamide resulted in
      superior therapeutic indices and maximal disease control. These findings
      highlight the potential of HSP90 inhibition as an alternative, and potentially
      complementary, strategy for therapeutic intervention in SLE. Such approaches may
      have important implications for disease management, particularly for limiting or
      preventing treatment-related toxicities, a major confounding factor in current
      SLE therapy. 

PMID- 25974044
TI  - Reply to why use tap water by Nagoba et al. - Explanation in physiological and
      microbiological view.

PMID- 25974045
TI  - Quantification of Protein Hydration, Glass Transitions, and Structural
      Relaxations of Aqueous Protein and Carbohydrate-Protein Systems.
AB  - Water distribution and miscibility of carbohydrate and protein components in
      biological materials and their structural contributions in concentrated solids
      are poorly understood. In the present study, structural relaxations and a glass
      transition of protein hydration water and antiplasticization of the hydration
      water at low temperatures were measured using dynamic mechanical analysis (DMA)
      and differential scanning calorimetry (DSC) for bovine whey protein (BWP),
      aqueous glucose-fructose (GF), and their mixture. Thermal transitions of alpha
      lactalbumin and beta-lactoglobulin components of BWP included water-content
      dependent endothermic but reversible dehydration and denaturation, and exothermic
      and irreversible aggregation. An alpha-relaxation assigned to hydration water in
      BWP appeared at water-content-dependent temperatures and increased to over the
      range of 150-200 K at decreasing water content and in the presence of GF. Two
      separate glass transitions and individual fractions of unfrozen water of ternary
      GF-BWP-water systems contributed to uncoupled alpha-relaxations, suggesting
      different roles of protein hydration water and carbohydrate vitrification in
      concentrated solids during freezing and dehydration. Hydration water in the BWP
      fraction of GF-BWP systems was derived from equilibrium water sorption and glass
      transition data of the GF fraction, which gave a significant universal method to
      quantify (i) protein hydration water and (ii) the unfrozen water in protein
      carbohydrate systems for such applications as cryopreservation, freezing,
      lyophilization, and dehydration of biological materials. A ternary supplemented
      phase diagram (state diagram) established for the GF-BWP-water system can be used
      for the analysis of the water distribution across carbohydrate and protein
      components in such applications. 

PMID- 25974046
TI  - The more we know, the more we have to discover: an exciting future for
      understanding cilia and ciliopathies.
AB  - The Cilia 2014 conference was organised by four European networks: the Ciliopathy
      Alliance, the Groupement de Recherche CIL, the Nordic Cilia and Centrosome
      Network and the EU FP7 programme SYSCILIA. More than 400 delegates from 27
      countries gathered at the Institut Pasteur conference centre in Paris, including
      30 patients and patient representatives. The meeting offered a unique opportunity
      for exchange between different scientific and medical communities. Major
      highlights included new discoveries about the roles of motile and immotile cilia
      during development and homeostasis, the mechanism of cilium construction, as well
      as progress in diagnosis and possible treatment of ciliopathies. The
      contributions to the cilia field of flagellated infectious eukaryotes and of
      systems biology were also presented. 

PMID- 25974047
TI  - Magnetic Transition to Antiferromagnetic Phase in Gadolinium Substituted
      Topological Insulator Bi2Te3.
AB  - There are many interests to achieve long-range magnetic order in topological
      insulators of Bi2Se3 or Bi2Te3 by doping magnetic transition metals such as Fe
      and Mn. The transition metals act as not only magnetic dopants but also electric
      dopants because they are usually divalent. However, if the doping elements are
      rare-earth metals such as Gd, which are trivalent, only magnetic moments can be
      introduced. We fabricated single crystals of Bi2-xGdxTe3 (0 <= * <= 0.2), in
      which we observed magnetic phase change from paramagnetic (PM) to
      antiferromagnetic (AFM) phase by increasing x. This PM-to-AFM phase transition
      agrees with the density functional theory calculations showing a weak and short
      ranged Gd-Gd AFM coupling via the intervening Te ions. The critical point
      corresponding to the magnetic phase transition is x = 0.09, where large linear
      magnetoresistance and highly anisotropic Shubnikov-de Haas oscillations are
      observed. These results are discussed with two-dimensional properties of
      topological surface state electrons. 

PMID- 25974048
TI  - Alkalization is responsible for antibacterial effects of corroding magnesium.
AB  - Magnesium alloys are presently investigated as potential medical implant
      materials for temporary applications. Magnesium has been reported to have
      antibacterial activities and could therefore be used to prevent antibiotic
      treatment-resistant bacterial implant infections. For characterizing the effects
      of magnesium on infectious bacteria, bioluminescent S. aureus or P. aeruginosa
      were employed. The proliferation of both types of bacteria was suppressed in the
      presence of metallic magnesium and also in aqueous magnesium corrosion extracts.
      Of the two soluble corrosion products, magnesium ions were well tolerated while
      antibacterial activities correlated with increased pH levels of the supernatants.
      The alkaline pH alone was sufficient for the antibacterial effects which were
      completely abolished when the pH of the corrosion supernatants was neutralized.
      These results demonstrate that pH increases are necessary and sufficient for the
      antibacterial activity of metallic magnesium. In an animal model magnesium
      implants showed an enhanced but variable resistance to bacterial colonization.

PMID- 25974050
TI  - Ab Initio Kinetics of Hydrogen Abstraction from Methyl Acetate by Hydrogen,
      Methyl, Oxygen, Hydroxyl, and Hydroperoxy Radicals.
AB  - The kinetics of hydrogen abstraction by five radicals (H, O((3)P), OH, CH3, and
      HO2) from methyl acetate (MA) is investigated theoretically in order to gain
      further understanding of certain aspects of the combustion chemistry of
      biodiesels, such as the effect of the ester moiety. We employ ab initio quantum
      chemistry methods, coupled cluster singles and doubles with perturbative triples
      correction (CCSD(T)) and multireference averaged coupled pair functional theory
      (MRACPF2), to predict chemically accurate reaction energetics. Overall, MRACPF2
      predicts slightly higher barrier heights than CCSD(T) for MA + H/CH3/O/OH, but
      slightly lower barrier heights for hydrogen abstraction by HO2. Based on the
      obtained reaction energies, we also report high-pressure-limit rate constants
      using transition state theory (TST) in conjunction with the separable-hindered
      rotor approximation, the variable reaction coordinate TST, and the multi
      structure all-structure approach. The fitted modified Arrhenius expressions are
      provided over a temperature range of 250 to 2000 K. The predictions are in good
      agreement with available experimental results. Abstractions from both of the
      methyl groups in MA are expected to contribute to consumption of the fuel as they
      exhibit similar rate coefficients. The reactions involving the OH radical are
      predicted to have the highest rates among the five abstracting radicals, while
      those initiated by HO2 are expected to be the lowest. 

PMID- 25974049
TI  - Effect of a high-intensity exercise program on physical function and mental
      health in nursing home residents with dementia: an assessor blinded randomized
      controlled trial.
AB  - BACKGROUND: Dementia is among the leading causes of functional loss and
      disability in older adults. Research has demonstrated that nursing home patients
      without dementia can improve their function in activities of daily living,
      strength, balance and mental well being by physical exercise. The evidence on
      effect of physical exercise among nursing home patients with dementia is scarce
      and ambiguous. Thus, the primary objective of this study was to investigate the
      effect of a high intensity functional exercise program on the performance of
      balance in nursing home residents with dementia. The secondary objective was to
      examine the effect of this exercise on muscle strength, mobility, activities of
      daily living, quality of life and neuropsychiatric symptoms. DESIGN AND METHODS:
      This single blinded randomized controlled trial was conducted among 170 persons
      with dementia living in nursing homes. Mean age was 86.7 years (SD = 7.4) and 74%
      were women. The participants were randomly allocated to an intervention (n = 87)
      or a control group (n = 83). The intervention consisted of intensive
      strengthening and balance exercises in small groups twice a week for 12 weeks.
      The control condition was leisure activities. RESULTS: The intervention group
      improved the score on Bergs Balance Scale by 2.9 points, which was significantly
      more than the control group who improved by 1.2 points (p = 0.02). Having
      exercised 12 times or more was significantly associated with improved strength
      after intervention (p<0.05). The level of apathy was lower in the exercise group
      after the intervention, compared to the control group (p = 0.048). CONCLUSION:
      The results from our study indicate that a high intensity functional exercise
      program improved balance and muscle strength as well as reduced apathy in nursing
      home patients with dementia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02262104.

PMID- 25974053
TI  - Risk factors associated with psychiatric readmission.
AB  - The present study focused on identifying risk factors for early readmission of
      patients discharged from an urban community hospital. Retrospective chart reviews
      were conducted on 207 consecutive inpatient psychiatric admissions that included
      patients who were readmitted within 15 days, within 3 to 6 months, and not
      admitted for at least 12 months post-discharge. Findings indicated that a
      diagnosis of schizophrenia/schizoaffective disorder (OR = 18; 95% CI 2.70-117.7;
      p < 0.05), history of alcohol abuse (OR = 9; 95% CI 1.80-40.60; p < 0.05), number
      of previous psychiatric hospitalizations (OR = 2; 95% CI 1.28-3.73; p < 0.05),
      and type of residence at initial admission (e.g., homeless, OR = 29; 95% CI 3.99
      217; p < 0.05) were significant risk factors for early readmission, where OR
      compares readmission group 1 versus group 3 in the multinomial logistic
      regression. Initial positive urine drug screen, history of drug abuse or
      incarceration, and legal status at initial admission did not predict early
      readmission. Reducing the risk factors associated with psychiatric readmissions
      has the potential to lead to the identification and development of preventative
      intervention strategies that can significantly improve patient safety, quality of
      care, well-being, and contain health care expenditures.

PMID- 25974052
TI  - Decoding size distribution patterns in marine and transitional water
      phytoplankton: from community to species level.
AB  - Understanding the mechanisms of phytoplankton community assembly is a fundamental
      issue of aquatic ecology. Here, we use field data from transitional (e.g. coastal
      lagoons) and coastal water environments to decode patterns of phytoplankton size
      distribution into organization and adaptive mechanisms. Transitional waters are
      characterized by higher resource availability and shallower well-mixed water
      column than coastal marine environments. Differences in physico-chemical regime
      between the two environments have been hypothesized to exert contrasting
      selective pressures on phytoplankton cell morphology (size and shape). We tested
      the hypothesis focusing on resource availability (nutrients and light) and mixed
      layer depth as ecological axes that define ecological niches of phytoplankton. We
      report fundamental differences in size distributions of marine and freshwater
      diatoms, with transitional water phytoplankton significantly smaller and with
      higher surface to volume ratio than marine species. Here, we hypothesize that
      mixing condition affecting size-dependent sinking may drive phytoplankton size
      and shape distributions. The interplay between shallow mixed layer depth and
      frequent and complete mixing of transitional waters may likely increase the
      competitive advantage of small phytoplankton limiting large cell fitness. The
      nutrient regime appears to explain the size distribution within both marine and
      transitional water environments, while it seem does not explain the pattern
      observed across the two environments. In addition, difference in light
      availability across the two environments appear do not explain the occurrence of
      asymmetric size distribution at each hierarchical level. We hypothesize that such
      competitive equilibria and adaptive strategies in resource exploitation may drive
      by organism's behavior which exploring patch resources in transitional and marine
      phytoplankton communities. 

PMID- 25974051
TI  - Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via
      Facilitating Iron Uptake from Ferrioxamine.
AB  - Dialysis patients with chronic renal failure receiving deferoxamine for treating
      iron overload are uniquely predisposed for mucormycosis, which is most often
      caused by Rhizopus oryzae. Although the deferoxamine siderophore is not secreted
      by Mucorales, previous studies established that Rhizopus species utilize iron
      from ferrioxamine (iron-rich form of deferoxamine). Here we determined that the
      CBS domain proteins of Fob1 and Fob2 act as receptors on the cell surface of R.
      oryzae during iron uptake from ferrioxamine. Fob1 and Fob2 cell surface
      expression was induced in the presence of ferrioxamine and bound radiolabeled
      ferrioxamine. A R. oryzae strain with targeted reduced Fob1/Fob2 expression was
      impaired for iron uptake, germinating, and growing on medium with ferrioxamine as
      the sole source of iron. This strain also exhibited reduced virulence in a
      deferoxamine-treated, but not the diabetic ketoacidotic (DKA), mouse model of
      mucormycosis. The mechanism by which R. oryzae obtains iron from ferrioxamine
      involves the reductase/permease uptake system since the growth on ferrioxamine
      supplemented medium is associated with elevated reductase activity and the use of
      the ferrous chelator bathophenanthroline disulfonate abrogates iron uptake and
      growth on medium supplemented with ferrioxamine as a sole source of iron.
      Finally, R. oryzae mutants with reduced copies of the high affinity iron permease
      (FTR1) or with decreased FTR1 expression had an impaired iron uptake from
      ferrioxamine in vitro and reduced virulence in the deferoxamine-treated mouse
      model of mucormycosis. These two receptors appear to be conserved in Mucorales,
      and can be the subject of future novel therapy to maintain the use of
      deferoxamine for treating iron-overload. 

PMID- 25974054
TI  - The relation between eating disorder symptoms and impairment.
AB  - Although a number of studies have looked at what factors might mediate the
      relationship between symptoms and quality of life (QoL) in a number of
      psychiatric disorders, little research has addressed this issue in eating
      disorders. In the current study, female undergraduates (N = 339) completed
      questionnaires assessing eating disorder symptoms, social support, coping, QoL,
      and psychosocial impairment. Perceived family support and levels of substance
      misuse as a way of coping were identified as mediators of the symptom-impairment
      relationship and, in addition, maladaptive coping also mediated the relationship
      with QoL. These results highlight the role of coping and social support in
      impairment resulting from eating disorder symptoms.

PMID- 25974055
TI  - Assessment of clinical information: Comparison of the validity of a Structured
      Clinical Interview (the SCID) and the Clinical Diagnostic Interview.
AB  - Adaptive functioning is a key aspect of psychiatric diagnosis and assessment in
      research and practice. This study compared adaptive functioning validity ratings
      from Structured Clinical Interviews (SCIDs, symptom-focused structured diagnostic
      interviews), and Clinical Diagnostic Interviews (CDIs, systematic diagnostic
      interviews modeling naturalistic clinical interactions focusing on relational
      narratives). Two hundred forty-five patients (interviewed by two independent
      interviewers) and their interviewers completed the Clinical Data Form which
      assesses adaptive functioning and clinical information. Both interviews converged
      strongly with patient-reports, with no significant differences in validity of the
      interviews in measuring global and specific domains of adaptive functioning
      variables. Findings suggest that CDIs provide adaptive functioning data
      comparable to SCIDs (often considered "gold standard" for assessment but
      difficult to use in practice) and have important implications for bridging the
      research-practice gap. By incorporating clinicians' everyday methods, CDIs yield
      information that is psychometrically sound for empirical investigation,
      diagnostically practical, and clinically meaningful and valid.

PMID- 25974056
TI  - Sleep disturbance and attempted suicide in rural China: a case-control study.
AB  - This study aimed to examine the association between sleep disturbance and
      attempted suicide in rural China. The study group included 409 suicide attempters
      from six rural counties in Shandong Province, China and an equal number of
      controls matched on age, sex, and residency. Sleep disturbance was assessed by
      the item "sleep restless" in the Center for Epidemiologic Studies Depression
      Scale. Sleep disturbance was reported more frequently in suicide attempters than
      in controls (1-2 days/week, 9.0% vs. 4.4%; 3-4 days/week, 11.5% vs. 2.4%; >=5
      days/week, 30.3% vs. 7.5%, chi 2= 128.72, p < 0.001). Suicide risk was
      significantly associated with increased frequency of sleep disturbance (OR =
      3.98, 95% CI = 1.62-9.74 for 1-2 days/week; OR = 3.28, 95% CI = 1.21-8.84 for 3-4
      days/week; OR = 2.41, 95% CI = 1.26-4.60 for >=5 days/week) even after adjusting
      for potential psychosocial confounding factors and mental disorders. This finding
      may have important implications for early intervention and prevention of suicide.

PMID- 25974057
TI  - Dissociation in individuals denying trauma exposure: findings from two samples.
AB  - A number of studies suggest that dissociation is reliably related to trauma
      exposure, and that inadequate regulation of posttraumatic distress may be a
      significant factor. We examined whether affect dysregulation predicts
      dissociation in those denying any lifetime exposure to trauma. These
      relationships were evaluated in a general population sample and a second sample
      of nontraumatized university students. In the first study, multivariate analyses
      indicated that, along with gender, affect dysregulation was a relatively strong
      predictor, accounting for 27% of the variance in dissociation. In the replication
      study, dissociation was associated with affect dysregulation, but not gender.
      Affect dysregulation seems to predict dissociative symptomatology in
      nontraumatized individuals. It is hypothesized that emotional distress, whether
      from trauma or other etiologies, motivates dissociation to the extent that it
      challenges the individual's compromised capacity for affect regulation. Treatment
      implications may include the potential helpfulness of interventions that increase
      emotion regulation skills.

PMID- 25974058
TI  - Decrease of functioning in remitted and non-remitted patients 16 years after a
      first-episode schizophrenia.
AB  - In schizophrenia, a better level of functioning has been generally associated
      with symptomatic remission. However, this association has been supported by cross
      sectional studies or by studies with a short follow-up period. Forty-eight
      patients with schizophrenia were evaluated by the Positive and Negative Symptoms
      Scale and the Social and Occupational Functioning Assessment Scale (SOFAS) at the
      first episode and after a mean period of 16 years. At follow-up, patients were
      defined as remitters (R) or non-remitters (NR) according to the Remission
      Schizophrenia Working Group criteria. R (n = 18; 37.5%) compared to NR showed at
      the first episode a lower illness severity and a better level of functioning. A
      functional decline was found in both groups at follow-up, even though NR showed a
      more than twofold reduction than R. Better SOFAS scores at follow-up were
      predicted by baseline SOFAS score and less severe negative symptoms at follow-up.
      Schizophrenia implies a functional decline over time, regardless of the
      symptomatic remission status with negative symptoms playing a major role.

PMID- 25974059
TI  - Eye movement desensitization and reprocessing versus cognitive-behavioral therapy
      for adult posttraumatic stress disorder: systematic review and meta-analysis.
AB  - Posttraumatic stress disorder (PTSD) is a relatively common mental disorder, with
      an estimated lifetime prevalence of ~5.7%. Eye movement desensitization and
      reprocessing (EMDR) and cognitive-behavioral therapy (CBT) are the most often
      studied and most effective psychotherapies for PTSD. However, evidence is
      inadequate to conclude which treatment is superior. Therefore, we conducted a
      meta-analysis to confirm the effectiveness of EMDR compared to CBT for adult
      PTSD. We searched Medline, PubMed, Ebsco, Proquest, and Cochrane (1989-2013) to
      identify relevant randomized control trials comparing EMDR and CBT for PTSD. We
      included 11 studies (N = 424). Although all the studies had methodological
      limitations, meta-analyses for total PTSD scores revealed that EMDR was slightly
      superior to CBT. Cumulative meta-analysis confirmed this and a meta-analysis for
      subscale scores of PTSD symptoms indicated that EMDR was better for decreased
      intrusion and arousal severity compared to CBT. Avoidance was not significantly
      different between groups. EMDR may be more suitable than CBT for PTSD patients
      with prominent intrusion or arousal symptoms. However, the limited number and
      poor quality of the original studies included suggest caution when drawing final
      conclusions.

PMID- 25974060
TI  - Adolescent and mid-life diet and subsequent risk of thyroid cancer in the NIH
      AARP diet and health study.
AB  - Although thyroid cancer is suspected to have a nutritional etiology, prospective
      studies examining the relationship between diet and thyroid cancer are lacking.
      During 1996-1997, NIH-AARP Diet and Health Study participants, ages 51-72 years,
      completed a 37-item food frequency questionnaire about diet at ages 12-13 years
      (adolescence) and 10 years before baseline (mid-life). Over a median 10 years of
      follow-up, 325 individuals (143 men and 182 women) were diagnosed with thyroid
      cancer. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals
      (CIs) were calculated for intakes of foods and food groups comparing the highest
      to the lowest quartiles. Adolescent intakes of chicken/turkey (HR = 1.59, 95% CI:
      0.97-2.60; ptrend  < 0.01) and sweet baked goods (HR = 1.59, 95% CI: 1.09-2.34;
      ptrend  = 0.04) were positively associated with thyroid cancer risk, while intake
      of butter/margarine was inversely associated with risk (HR = 0.64, 95% CI: 0.44
      0.91; ptrend  < 0.02). Similar to adolescent diet, mid-life intake of sweet baked
      goods was nonsignificantly associated with an increased risk of thyroid cancer
      (HR = 1.39, 95% CI: 0.96-2.00; ptrend  = 0.11), but intake of butter/margarine
      was inversely associated with risk (HR = 0.66, 95% CI: 0.46-0.95; ptrend  =
      0.03). Among men, higher adolescent consumption of canned tuna was positively
      associated with risk of thyroid cancer (HR = 1.69, 95% CI: 1.01-2.83; ptrend  =
      0.03), and greater mid-life intake of broccoli was associated with a twofold
      increased risk (HR = 2.13, 95% CI: 1.13-3.99; ptrend  < 0.01). This large
      prospective study suggests that several components of the adolescent and mid-life
      diet, including iodine-rich foods and goitrogens, may influence thyroid cancer
      risk.

PMID- 25974061
TI  - Phytohormone Profiling across the Bryophytes.
AB  - BACKGROUND: Bryophytes represent a very diverse group of non-vascular plants such
      as mosses, liverworts and hornworts and the oldest extant lineage of land plants.
      Determination of endogenous phytohormone profiles in bryophytes can provide
      substantial information about early land plant evolution. In this study, we
      screened thirty bryophyte species including six liverworts and twenty-four mosses
      for their phytohormone profiles in order to relate the hormonome with phylogeny
      in the plant kingdom. METHODOLOGY: Samples belonging to nine orders (Pelliales,
      Jungermanniales, Porellales, Sphagnales, Tetraphidales, Polytrichales,
      Dicranales, Bryales, Hypnales) were collected in Central and Northern Bohemia.
      The phytohormone content was analysed with a high performance liquid
      chromatography electrospray tandem-mass spectrometry (HPLC-ESI-MS/MS). PRINCIPAL
      FINDINGS: As revealed for growth hormones, some common traits such as weak
      conjugation of both cytokinins and auxins, intensive production of cisZ-type
      cytokinins and strong oxidative degradation of auxins with abundance of a major
      primary catabolite 2-oxindole-3-acetic acid were pronounced in all bryophytes.
      Whereas apparent dissimilarities in growth hormones profiles between liverworts
      and mosses were evident, no obvious trends in stress hormone levels (abscisic
      acid, jasmonic acid, salicylic acid) were found with respect to the phylogeny.
      CONCLUSION: The apparent differences in conjugation and/or degradation strategies
      of growth hormones between liverworts and mosses might potentially show a hidden
      link between vascular plants and liverworts. On the other hand, the complement of
      stress hormones in bryophytes probably correlate rather with prevailing
      environmental conditions and plant survival strategy than with plant evolution.

PMID- 25974062
TI  - Simultaneous Enhancement of Electrical Conductivity and Thermopower of Bi2Te3 by
      Multifunctionality of Native Defects.
AB  - Simultaneous increases in electrical conductivity (up to 200%) and thermopower
      (up to 70%) are demonstrated by introducing native defects in Bi2 Te3 films,
      leading to a high power factor of 3.4 * 10(-3) W m(-1) K(-2). The maximum
      enhancement of the power factor occurs when the native defects act beneficially
      both as electron donors and energy filters to mobile electrons. They also act as
      effective phonon scatterers.

PMID- 25974064
TI  - The local electric field favours more than exposed nitrogen atoms on CO2 capture:
      a case study on the rht-type MOF platform.
AB  - Two rht-type metal-organic frameworks (MOFs) based upon the tetrazolate moiety
      and pyrazolate moiety, respectively, have been investigated for carbon dioxide
      (CO2) adsorption and selective adsorption of CO2 over CH4, which shows that the
      rht-MOF featuring the pyrazolate moiety demonstrates superior performances
      compared to the rht-MOF based on the tetrazolate moiety. In spite of more exposed
      nitrogen atoms in the tetrazolate-based rht-MOF, the counter-intuitive
      observations of CO2 capture in the two rht-MOFs were interpreted by computational
      studies, which reveal that the local electric field favours more than the
      richness of exposed nitrogen atoms for the interactions with CO2 molecules. 

PMID- 25974065
TI  - Correction: Risk Factors for Men's Lifetime Perpetration of Physical Violence
      against Intimate Partners: Results from the International Men and Gender Equality
      Survey (IMAGES) in Eight Countries.

PMID- 25974063
TI  - MR relaxometry for the facial ageing assessment: the preliminary study of the age
      dependency in the MR relaxometry parameters within the facial soft tissue.
AB  - OBJECTIVES: To investigate the location-specific tissue properties and age
      related changes of the facial fat and facial muscles using quantitative MRI
      (qMRI) analysis of longitudinal magnetization (T1) and transverse magnetization
      (T2) values. METHODS: 38 subjects (20 males and 18 females, 0.5-87 years old)
      were imaged with a mixed turbo-spin echo sequence at 1.5 T. T1 and T2
      measurements were obtained within regions of interest in six facial fat regions
      including the buccal fat and subcutaneous cheek fat, four eyelid fat regions
      (lateral upper, medial upper, lateral lower and medial lower) and five facial
      muscles including the orbicularis oculi, orbicularis oris, buccinator,
      zygomaticus major and masseter muscles bilaterally. RESULTS: Within the
      zygomaticus major muscle, age-associated T1 decreases in females and T1 increases
      in males were observed in later life with an increase in T2 values with age. The
      orbicularis oculi muscles showed lower T1 and higher T2 values compared to the
      masseter, orbicularis oris and buccinator muscles, which demonstrated small age
      related changes. The dramatic age-related changes were also observed in the
      eyelid fat regions, particularly within the lower eyelid fat; negative
      correlations with age in T1 values (p<0.0001 for age) and prominent positive
      correlation in T2 values in male subjects (p<0.0001 for male*age). Age-related
      changes were not observed in T2 values within the subcutaneous cheek fat.
      CONCLUSIONS: This study demonstrates proof of concept using T1 and T2 values to
      assess age-related changes of the facial soft tissues, demonstrating tissue
      specific qMRI measurements and non-uniform ageing patterns within different
      regions of facial soft tissues.

PMID- 25974066
TI  - Ameliorating effects and autonomic mechanisms of needle-less transcutaneous
      electrical stimulation at ST36 on stress-induced impairment in gastric slow
      waves.
AB  - BACKGROUND AND AIM: Stress has long been documented to alter gastrointestinal
      motility. The effects of electroacupuncture (EA) on stress and gastric motility
      are relatively well known; however, whether EA has an ameliorating effect on
      stress-induced dysmotility remained unclear. This study aims to investigate the
      effects and mechanisms of needle-less transcutaneous electroacupuncture (TEA) on
      stress-induced impairment in gastric slow waves. METHODS: A watch-size digital
      stimulator was developed. Ten healthy volunteers were involved in a four-session
      study (control, cold stress, TEA, and sham TEA). Electrogastrograpy was used to
      assess gastric slow waves, and electrocardiogram was recorded for the assessment
      of autonomic functions. The recordings were made in each session with/without
      stress and with TEA at ST36 or sham points. RESULTS: The results are as follows:
      (i) Cold stress-induced gastric dysrhythmia and impaired normal slow waves (P <
      0.01). TEA showed a preventive effect on cold stress-induced impairment in
      gastric slow waves. TEA at ST36, but not sham TEA, normalized slow waves (P =
      0.03 vs stress; P = 0.44 vs control), attributed to the suppression of gastric
      dysrhythmia; (ii) Postprandially, there was a decrease in vagal activity in both
      control (P = 0.004) and stress (P = 0.002) sessions; this decrease was prevented
      with TEA (P < 0.05). Similarly, there was a postprandial increase in sympathetic
      activity in both control (P = 0.01) and stress (P = 0.002) sessions, and this
      increase was suppressed with TEA. CONCLUSIONS: Needle-less TEA at ST36 using a
      watch-size stimulator is able to improve stress-induced impairment in gastric
      slow waves, possibly mediated via the autonomic mechanism. Home-based needle-less
      TEA may be a viable therapy for stress-induced impairment in gastric motility
      functions.

PMID- 25974067
TI  - Schinus terebinthifolius Leaf Extract Causes Midgut Damage, Interfering with
      Survival and Development of Aedes aegypti Larvae.
AB  - In this study, a leaf extract from Schinus terebinthifolius was evaluated for
      effects on survival, development, and midgut of A. aegypti fourth instar larvae
      (L4), as well as for toxic effect on Artemia salina. Leaf extract was obtained
      using 0.15 M NaCl and evaluated for phytochemical composition and lectin
      activity. Early L4 larvae were incubated with the extract (0.3-1.35%, w/v) for 8
      days, in presence or absence of food. Polymeric proanthocyanidins, hydrolysable
      tannins, heterosid and aglycone flavonoids, cinnamic acid derivatives, traces of
      steroids, and lectin activity were detected in the extract, which killed the
      larvae at an LC50 of 0.62% (unfed larvae) and 1.03% (fed larvae). Further, the
      larvae incubated with the extract reacted by eliminating the gut content. No
      larvae reached the pupal stage in treatments at concentrations between 0.5% and
      1.35%, while in the control (fed larvae), 61.7% of individuals emerged as adults.
      The extract (1.0%) promoted intense disorganization of larval midgut epithelium,
      including deformation and hypertrophy of cells, disruption of microvilli, and
      vacuolization of cytoplasms, affecting digestive, enteroendocrine, regenerative,
      and proliferating cells. In addition, cells with fragmented DNA were observed.
      Separation of extract components by solid phase extraction revealed that cinnamic
      acid derivatives and flavonoids are involved in larvicidal effect of the extract,
      being the first most efficient in a short time after larvae treatment. The lectin
      present in the extract was isolated, but did not show deleterious effects on
      larvae. The extract and cinnamic acid derivatives were toxic to A. salina
      nauplii, while the flavonoids showed low toxicity. S. terebinthifolius leaf
      extract caused damage to the midgut of A. aegypti larvae, interfering with
      survival and development. The larvicidal effect of the extract can be attributed
      to cinnamic acid derivatives and flavonoids. The data obtained using A. salina
      indicates that caution should be used when employing this extract as a larvicidal
      agent. 

PMID- 25974068
TI  - Integrating transcriptome and genome re-sequencing data to identify key genes and
      mutations affecting chicken eggshell qualities.
AB  - Eggshell damages lead to economic losses in the egg production industry and are a
      threat to human health. We examined 49-wk-old Rhode Island White hens (Gallus
      gallus) that laid eggs having shells with significantly different strengths and
      thicknesses. We used HiSeq 2000 (Illumina) sequencing to characterize the chicken
      transcriptome and whole genome to identify the key genes and genetic mutations
      associated with eggshell calcification. We identified a total of 14,234 genes
      expressed in the chicken uterus, representing 89% of all annotated chicken genes.
      A total of 889 differentially expressed genes were identified by comparing low
      eggshell strength (LES) and normal eggshell strength (NES) genomes. The DEGs are
      enriched in calcification-related processes, including calcium ion transport and
      calcium signaling pathways as revealed by gene ontology (GO) and Kyoto
      encyclopedia of genes and genomes (KEGG) pathway analysis. Some important matrix
      proteins, such as OC-116, LTF and SPP1, were also expressed differentially
      between two groups. A total of 3,671,919 single-nucleotide polymorphisms (SNPs)
      and 508,035 Indels were detected in protein coding genes by whole-genome re
      sequencing, including 1775 non-synonymous variations and 19 frame-shift Indels in
      DEGs. SNPs and Indels found in this study could be further investigated for
      eggshell traits. This is the first report to integrate the transcriptome and
      genome re-sequencing to target the genetic variations which decreased the
      eggshell qualities. These findings further advance our understanding of eggshell
      calcification in the chicken uterus.

PMID- 25974069
TI  - Projection of young-old and old-old with functional disability: does accounting
      for the changing educational composition of the elderly population make a
      difference?
AB  - This study compares projections, up to year 2040, of young-old (aged 60-79) and
      old-old (aged 80+) with functional disability in Singapore with and without
      accounting for the changing educational composition of the Singaporean elderly.
      Two multi-state population models, with and without accounting for educational
      composition respectively, were developed, parameterized with age-gender
      (education)-specific transition probabilities (between active, functional
      disability and death states) estimated from two waves (2009 and 2011) of a
      nationally representative survey of community-dwelling Singaporeans aged >= 60
      years (N=4,990). Probabilistic sensitivity analysis with the bootstrap method was
      used to obtain the 95% confidence interval of the transition probabilities. Not
      accounting for educational composition overestimated the young-old with
      functional disability by 65 percent and underestimated the old-old by 20 percent
      in 2040. Accounting for educational composition, the proportion of old-old with
      functional disability increased from 40.8 percent in 2000 to 64.4 percent by
      2040; not accounting for educational composition, the proportion in 2040 was 49.4
      percent. Since the health profiles, and hence care needs, of the old-old differ
      from those of the young-old, health care service utilization and expenditure and
      the demand for formal and informal caregiving will be affected, impacting health
      and long-term care policy.

PMID- 25974070
TI  - Macro-economic conditions and infant health: a changing relationship for black
      and white infants in the United States.
AB  - We study whether the relationship between the state unemployment rate at the time
      of conception and infant health, infant mortality and maternal characteristics in
      the United States has changed over the years 1980-2004. We use microdata on
      births and deaths for years 1980-2004 and find that the relationship between the
      state unemployment rate at the time of conception and infant mortality and
      birthweight changes over time and is stronger for blacks than whites. For years
      1980-1989 increases in the state unemployment rate are associated with a decline
      in infant mortality among blacks, an effect driven by mortality from gestational
      development and birth weight, and complications of placenta while in utero. In
      contrast, state economic conditions are unrelated to black infant mortality in
      years 1990-2004 and white infant mortality in any period, although effects vary
      by cause of death. We explore potential mechanisms for our findings and,
      including mothers younger than 18 in the analysis, uncover evidence of age
      related maternal selection in response to the business cycle. In particular, in
      years 1980-1989 an increase in the unemployment rate at the time of conception is
      associated with fewer babies born to young mothers. The magnitude and direction
      of the relationship between business cycles and infant mortality differs by race
      and period. Age-related selection into motherhood in response to the business
      cycle is a possible explanation for this changing relationship. 

PMID- 25974071
TI  - A multicenter, randomized, controlled trial of osteopathic manipulative treatment
      on preterms.
AB  - BACKGROUND: Despite some preliminary evidence, it is still largely unknown
      whether osteopathic manipulative treatment improves preterm clinical outcomes.
      MATERIALS AND METHODS: The present multi-center randomized single blind parallel
      group clinical trial enrolled newborns who met the criteria for gestational age
      between 29 and 37 weeks, without any congenital complication from 3 different
      public neonatal intensive care units. Preterm infants were randomly assigned to
      usual prenatal care (control group) or osteopathic manipulative treatment (study
      group). The primary outcome was the mean difference in length of hospital stay
      between groups. RESULTS: A total of 695 newborns were randomly assigned to either
      the study group (n= 352) or the control group (n=343). A statistical significant
      difference was observed between the two groups for the primary outcome (13.8 and
      17.5 days for the study and control group respectively, p<0.001, effect size:
      0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days
      (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions
      with treatment as compared to usual care in cost (difference between study and
      control group: 1,586.01?; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily
      weight gain. There were no complications associated to the intervention.
      CONCLUSIONS: Osteopathic treatment reduced significantly the number of days of
      hospitalization and is cost-effective on a large cohort of preterm infants.

PMID- 25974072
TI  - Comparing Near-Infrared Imaging with Indocyanine Green to Conventional Imaging
      During Laparoscopic Cholecystectomy: A Prospective Crossover Study.
AB  - BACKGROUND: The aim of this study was to test and validate a novel noninvasive
      method for intraoperative visualization of extrahepatic bile ducts during
      laparoscopic cholecystectomy. Injury to the common bile duct (CBD) is a rare but
      major complication of laparoscopic cholecystectomy. Most injuries occur when
      anatomy is unclear due to the presence of anatomic variations, acute
      inflammation, or adhesions. PATIENTS AND METHODS: Thirty patients were included,
      and each received an intravenous injection of 0.05 mg/kg of indocyanine green
      (ICG) (ICG-Pulsion((r)); PULSION Medical Systems AG, Munich, Germany) prior to
      the start of surgery. Laparoscopic cholecystectomy was performed according to
      standard procedures. The CBD and cystic duct (CD) were visualized before and
      during dissection of the liver hilus using a conventional laparoscopic camera and
      a recently developed near-infrared (NIR) camera (Olympus, Tokyo, Japan). RESULTS:
      Using ICG-NIR, the CBD and CD could be visualized 11 minutes (P=.008) and 8.6
      minutes (P=.001) earlier than with a conventional camera. Both early (20/30
      patients) and late (26/30 patients) identification of the CBD with ICG-NIR was
      significantly more frequent compared with conventional images (2/30 and 10/30,
      respectively; P<.001). One postoperative bilioma required re-admission and
      endoscopic retrograde cholangiopancreatography with stent placement. CONCLUSIONS:
      Identification of the CBD and CD using a low dose of ICG and the NIR camera was
      both faster and more frequent compared with conventional laparoscopic images
      during elective laparoscopic cholecystectomy.

PMID- 25974073
TI  - Kikuchi disease, macrophage activation syndrome, and systemic juvenile arthritis:
      a new case associated with a mutation in the perforin gene.

PMID- 25974074
TI  - A study of thermal dose-induced autophagy, apoptosis and necroptosis in colon
      cancer cells.
AB  - PURPOSE: The pleiotropic effects of heat on cancer cells have been well
      documented. The biological effects seen depend on the temperature applied, and
      the heating duration. In this study we investigate the cytotoxic effects of heat
      on colon cancer cells and determine how different cell death processes such as
      autophagy, apoptosis and necroptosis play a role in cell response. MATERIALS AND
      METHODS: The thermal dose concept was used to provide a parameter that will allow
      comparison of different thermal treatments. Two human colon cancer cell lines,
      HCT116 and HT29, were subjected to ablative temperatures using a polymerase chain
      reaction thermal cycler. Temperature was recorded using thermocouples. Cell
      viability was assessed using the MTT assay. Induction of apoptosis was estimated
      using an enzyme-linked immunosorbent assay that detects cleaved cytoplasmic
      nucleosomes. Protein regulation was determined using immunoblotting. The
      percentage of cells undergoing apoptosis and autophagy was determined with
      annexin V/propidium iodide staining and a cationic amphiphilic tracer using
      fluorescence-activated cell sorting analysis. RESULTS: Exposure of colon cancer
      cells to ablative thermal doses results in decreased cell viability. The
      cytotoxic effect of heat is associated with induction of apoptosis and autophagy,
      the amount depending on both the thermal dose applied and on the time elapsed
      after treatment. Autophagy induction is mainly seen in live cells. RIPK3 protein
      levels are increased after exposure of cells to heat. A necroptosis inhibitor
      does not affect cell viability. CONCLUSIONS: Autophagy, apoptosis and necroptosis
      are associated with the response of these cancer cell lines to supra-normal
      temperatures.

PMID- 25974075
TI  - Effect of Pulmonary Vein Anatomy and Pulmonary Vein Diameters on Outcome of
      Cryoballoon Catheter Ablation for Atrial Fibrillation.
AB  - BACKGROUND: In this study, we aimed to determine pulmonary vein (PV) variation
      patterns in patients undergoing cryoballoon ablation for atrial fibrillation (AF)
      and their impacts on procedural success and recurrence and also to identify
      predictors for recurrence. METHODS: We enrolled 54 patients with AF and having
      symptoms despite medical therapy. Prior to the procedure, PV variation and left
      atrium (LA) size were evaluated in all patients by computed tomography scan.
      Ablation procedure was performed with single balloon and predictors for AF
      recurrence were determined. RESULTS: The study population consisted of 54
      patients (male: 50 [27%], mean age: 53 +/- 12) with AF. Paroxysmal AF and
      persistent AF were detected in 55.6% (30) and 44.4% (24) of the patients,
      respectively. Mean procedural and fluoroscopy times were 73 +/- 19 minutes and 16
      +/- 4 minutes, respectively. The number of the patients with PV variation of
      right pulmonary vein (RPV) with >2 ostia and accessory PV was 27.8% (15) and
      18.5% (10). During the follow-up, 20.4% (11) of patients had AF recurrence.
      Patients with recurrence had greater transverse LA size (62 +/- 6 mm vs 57 +/- 5
      mm, P: 0014), longitudinal LA size (65 +/- 5 mm vs 61 +/- 6 mm, P: 0025), LA
      volume (78 +/- 17 mL vs 65 +/- 14 mL, P: 0011), fluoroscopy time (20.4 +/- 4.6
      minutes vs 15.7 +/- 3.5 minutes, P: 0001), RPV with >2 ostia (72.7% vs 27.3%, P:
      0001), right upper pulmonary vein (RUPV) diameter (21.6 +/- 2.8 cm vs 15.8 +/-
      2.1 cm; P < 0001), and persistent AF (33.3% vs 66.7%, P: 0046). In multivariate
      analysis, RUPV diameter (beta: 1006; P: 0010; odds ratio [OR]: 2736; 95%
      confidence interval [CI]: [1267-5906]) and fluoroscopy time (beta: 0327; P: 0050;
      OR: 1386; 95% CI: [1000-1921]) were determined as independent predictors for AF
      recurrence. CONCLUSIONS: Transverse and longitudinal LA size, LA volume,
      fluoroscopy time, presence of persistent AF, RUPV size, and the number of RPV
      ostia are associated with AF recurrence following cryoballoon-based ablation.
      RUPV size and fluoroscopy time are predictors for recurrence.

PMID- 25974076
TI  - Mechanisms of stage-transcending protection following immunization of mice with
      late liver stage-arresting genetically attenuated malaria parasites.
AB  - Malaria, caused by Plasmodium parasite infection, continues to be one of the
      leading causes of worldwide morbidity and mortality. Development of an effective
      vaccine has been encumbered by the complex life cycle of the parasite that has
      distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian
      host. Historically, malaria vaccine development efforts have targeted each stage
      in isolation. An ideal vaccine, however, would target multiple life cycle stages
      with multiple arms of the immune system and be capable of eliminating initial
      infection in the liver, the subsequent blood stage infection, and would prevent
      further parasite transmission. We have previously shown that immunization of mice
      with Plasmodium yoelii genetically attenuated parasites (GAP) that arrest late in
      liver stage development elicits stage-transcending protection against both a
      sporozoite challenge and a direct blood stage challenge. Here, we show that this
      immunization strategy engenders both T- and B-cell responses that are essential
      for stage-transcending protection, but the relative importance of each is
      determined by the host genetic background. Furthermore, potent anti-blood stage
      antibodies elicited after GAP immunization rely heavily on FC-mediated functions
      including complement fixation and FC receptor binding. These protective
      antibodies recognize the merozoite surface but do not appear to recognize the
      immunodominant merozoite surface protein-1. The antigen(s) targeted by stage
      transcending immunity are present in both the late liver stages and blood stage
      parasites. The data clearly show that GAP-engendered protective immune responses
      can target shared antigens of pre-erythrocytic and erythrocytic parasite life
      cycle stages. As such, this model constitutes a powerful tool to identify novel,
      protective and stage-transcending T and B cell targets for incorporation into a
      multi-stage subunit vaccine. 

PMID- 25974077
TI  - Prevalence of dyslipidaemia and associated risk factors in a rural population in
      South-Western Uganda: a community based survey.
AB  - BACKGROUND: The burden of dyslipidaemia is rising in many low income countries.
      However, there are few data on the prevalence of, or risk factors for,
      dyslipidaemia in Africa. METHODS: In 2011, we used the WHO Stepwise approach to
      collect cardiovascular risk data within a general population cohort in rural
      south-western Uganda. Dyslipidaemia was defined by high total cholesterol (TC) >=
      5.2 mmol/L or low high density lipoprotein cholesterol (HDL-C) <1 mmol/L in men,
      and <1.3 mmol/L in women. Logistic regression was used to explore correlates of
      dyslipidaemia. RESULTS: Low HDL-C prevalence was 71.3% and high TC was 6.0%. In
      multivariate analysis, factors independently associated with low HDL-C among both
      men and women were: decreasing age, tribe (prevalence highest among Rwandese
      tribe), lower education, alcohol consumption (comparing current drinkers to never
      drinkers: men adjusted (a)OR=0.44, 95%CI=0.35-0.55; women aOR=0.51, 95%CI=0.41
      0.64), consuming <5 servings of fruit/vegetable per day, daily vigorous physical
      activity (comparing those with none vs those with 5 days a week: men aOR=0.83
      95%CI=0.67-1.02; women aOR=0.76, 95%CI=0.55-0.99), blood pressure (comparing
      those with hypertension to those with normal blood pressure: men aOR=0.57,
      95%CI=0.43-0.75; women aOR=0.69, 95%CI=0.52-0.93) and HIV infection (HIV infected
      without ART vs. HIV negative: men aOR=2.45, 95%CI=1.53-3.94; women aOR=1.88,
      95%CI=1.19-2.97). The odds of low HDL-C was also higher among men with high BMI
      or HbA1c <= 6%, and women who were single or with abdominal obesity. Among both
      men and women, high TC was independently associated with increasing age, non
      Rwandese tribe, high waist circumference (men aOR=5.70, 95%CI=1.97-16.49; women
      aOR=1.58, 95%CI=1.10-2.28), hypertension (men aOR=3.49, 95%CI=1.74-7.00; women
      aOR=1.47, 95%CI=0.96-2.23) and HbA1c >6% (men aOR=3.00, 95%CI=1.37-6.59; women
      aOR=2.74, 95%CI=1.77-4.27). The odds of high TC was also higher among married
      men, and women with higher education or high BMI. CONCLUSION: Low HDL-C
      prevalence in this relatively young rural population is high whereas high TC
      prevalence is low. The consequences of dyslipidaemia in African populations
      remain unclear and prospective follow-up is required.

PMID- 25974078
TI  - Effort versus Reward: Preparing Samples for Fungal Community Characterization in
      High-Throughput Sequencing Surveys of Soils.
AB  - Next generation fungal amplicon sequencing is being used with increasing
      frequency to study fungal diversity in various ecosystems; however, the influence
      of sample preparation on the characterization of fungal community is poorly
      understood. We investigated the effects of four procedural modifications to
      library preparation for high-throughput sequencing (HTS). The following
      treatments were considered: 1) the amount of soil used in DNA extraction, 2) the
      inclusion of additional steps (freeze/thaw cycles, sonication, or hot water bath
      incubation) in the extraction procedure, 3) the amount of DNA template used in
      PCR, and 4) the effect of sample pooling, either physically or computationally.
      Soils from two different ecosystems in Minnesota, USA, one prairie and one forest
      site, were used to assess the generality of our results. The first three
      treatments did not significantly influence observed fungal OTU richness or
      community structure at either site. Physical pooling captured more OTU richness
      compared to individual samples, but total OTU richness at each site was highest
      when individual samples were computationally combined. We conclude that standard
      extraction kit protocols are well optimized for fungal HTS surveys, but because
      sample pooling can significantly influence OTU richness estimates, it is
      important to carefully consider the study aims when planning sampling procedures.

PMID- 25974079
TI  - Synthesis of daumone derivatives and their antiangiogenic activities on
      chorioallantoic membrane.
AB  - Daumone, a dauer-inducing pheromone and a series of lipid derivatives were
      synthesized from daumone to investigate structure-activity trends. Lipid
      derivatives demonstrated potent in vivo antiangiogenic activity on the
      chorioallantoic membrane, which exceeded that of fumagillin and thalidomide as
      reference agents. Among the 11 synthetic compounds tested, new derivatives 3, 11
      and 13 showed the most potent antiangiogenic activity, which was twice that of
      fumagillin and thalidomide, replacing these as the most potent known
      antiangiogenic agents. 

PMID- 25974080
TI  - Thiosemicarbazone-Pt(II) Complex Causes a Growth Inhibitory Effect on Human
      Mesenchymal Stem Cells.
AB  - We showed di[3,5-diacetyl-1,2,4-triazolbis(4-cyclohexylthiosemicarbazonato)
      platinum(II)] complex, (W8), endowed with important antitumor properties. Here,
      we analysed whether W8 can affect human bone marrow-derived Mesenchymal Stem
      Cells, (hMSCs), involved in tissue repair, immunomodulatory properties and also
      capacity for homing to injure-tumor sites in ovarian cancer. Specifically, we
      analysed the effect of W8 on cell proliferation, response to scratch, and whether
      copper-derived cellular mechanism is used by this platinum(II) complex being
      studied. Results showed that W8 causes a significant inhibition of cell
      proliferation at uM concentration. This effect is directly related to the
      alteration of cytoskeletal proteins and inhibition of the response to scratch
      induced by the presence of foetal bovine serum. This strongly supports the notion
      of W8 triggers the energetic metabolism of hMSCs and adds an extra support by the
      results showing W8 relationship with the cellular copper ions. W8, acting in
      hMSCs, regulates in addition the inhibition of cell proliferation, the inhibition
      of tumor angiogenesis and metastasis.

PMID- 25974081
TI  - Growth, Challenges, and Solutions over 25 Years of Mectizan and the Impact on
      Onchocerciasis Control.

PMID- 25974082
TI  - Hepatitis C virus gene sequencing as a tool for precise genotyping in the era of
      new direct antiviral agents.

PMID- 25974083
TI  - In Situ Microscopic Observation of the Crystallization Process of Molecular
      Microparticles by Fluorescence Switching.
AB  - To clearly understand the solid-state amorphous-to-crystalline transformation is
      a long-standing challenge because such crystallization occuring in confined
      environments is difficult to observe directly. We developed an in situ and real
      time imaging procedure to record the interface evolution in a solid-state
      crystallization of molecular amorphous particles. The method, by employing a
      tetra-substituted ethene with novel morphology-dependent fluorescence, which can
      distinguish the interfaces between the crystalline and amorphous phase by
      fluorescence color, is a simple and practical method to probe the inner process
      of a molecular microparticle. The crystallization of amorphous microparticles in
      different cases was clearly recorded, where the perfect microparticles and those
      with defects demonstrate diverse destinies. The details disclosed in this
      observation will deepen the understanding for a series of solid-state
      crystallization that we know little about before. 

PMID- 25974086
TI  - The glycemic index: Reports of its demise have been exaggerated.

PMID- 25974085
TI  - Finding and tracing human MSC in 3D microenvironments with the photoconvertible
      protein Dendra2.
AB  - Mesenchymal Stem/Stromal Cells (MSC) are a promising cell type for cell-based
      therapies - from tissue regeneration to treatment of autoimmune diseases - due to
      their capacity to migrate to damaged tissues, to differentiate in different
      lineages and to their immunomodulatory and paracrine properties. Here, a simple
      and reliable imaging technique was developed to study MSC dynamical behavior in
      natural and bioengineered 3D matrices. Human MSC were transfected to express a
      fluorescent photoswitchable protein, Dendra2, which was used to highlight and
      follow the same group of cells for more than seven days, even if removed from the
      microscope to the incubator. This strategy provided reliable tracking in 3D
      microenvironments with different properties, including the hydrogels Matrigel and
      alginate as well as chitosan porous scaffolds. Comparison of cells mobility
      within matrices with tuned physicochemical properties revealed that MSC embedded
      in Matrigel migrated 64% more with 5.2 mg protein/mL than with 9.6 mg/mL and that
      MSC embedded in RGD-alginate migrated 51% faster with 1% polymer concentration
      than in 2% RGD-alginate. This platform thus provides a straightforward approach
      to characterize MSC dynamics in 3D and has applications in the field of stem cell
      biology and for the development of biomaterials for tissue regeneration. 

PMID- 25974087
TI  - Intramolecularly Bridged Calix[4]arenes with Pronounced Complexation Ability
      toward Neutral Compounds.
AB  - Regioselective derivatization via an organomercury intermediate allowed for the
      introduction of carboxylic acid functionality into the meta position of the
      calix[4]arene skeleton. Intramolecular Friedel-Crafts cyclization led to a novel
      type of calixarene containing a ketone bridging moiety. Subsequent attack of the
      ketone by organometallic compounds occurred selectively from outside providing
      tertiary alcohols with the OH group oriented inside the cavity. These compounds
      can complex neutral molecules both in the solid state (X-ray) and in solution
      (NMR) using the cooperative effect of hydrogen bonding (OH) and CH-pi
      interactions from within the cavity. 

PMID- 25974089
TI  - Understanding the host-pathogen interaction saves lives: lessons from vaccines
      and vaccinations.
AB  - Vaccines are one of the most successful and cost-effective public health tools
      employed to date, yet these benefits are only realized when the life-saving
      intervention reaches each and every targeted individual. Vaccine development is
      prioritized based on a number of factors such as health burden, feasibility, and
      determination of potential target populations. But only through an arduous
      process of pre-clinical development and progressive clinical trials does a
      vaccine become licensed and recommended for use. Once used in a wider and more
      diverse population safety issues, long-term impact and other unintended outcomes
      may become apparent, influencing policy modification. This commentary explores
      the role host-pathogen interaction plays in vaccine development and the
      operational and policy considerations that may impact vaccine success post
      licensure. 

PMID- 25974088
TI  - Enhancer of zeste homolog 2 as an independent prognostic marker for cancer: a
      meta-analysis.
AB  - BACKGROUND: Novel biomarkers are of particular interest for predicting cancer
      prognosis. This study aimed to explore the associations between enhancer of zeste
      homolog 2 (EZH2) and patient survival in various cancers. METHODS: Relevant
      literature was retrieved from PubMed and Web of Science databases. Pooled hazard
      ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were
      calculated. RESULTS: Forty-nine studies (8,050 patients) were included. High EZH2
      expression was significantly associated with shorter overall (hazard ratio [HR]
      1.74, 95% CI: 1.46-2.07), disease-free (HR 1.59, 95% CI: 1.27-1.99), metastasis
      free (HR 2.19, 95% CI: 1.38-3.47), progression-free (HR 2.53, 95% CI: 1.52-4.21),
      cancer-specific (HR 3.13, 95% CI: 1.70-5.74), and disease-specific (HR 2.29, 95%
      CI: 1.56-3.35) survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93
      2.06). Moreover, EZH2 expression significantly correlated with distant metastasis
      (OR 3.25, 95% CI: 1.07-9.87) in esophageal carcinoma; differentiation (OR 3.00,
      95% CI: 1.37-6.55) in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI:
      2.49-4.08) in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33
      6.09), estrogen receptor status (OR 0.15, 95% CI: 0.11-0.20) and progesterone
      receptor status (OR 0.30, 95% CI: 0.23-0.39) in breast cancer. CONCLUSIONS: Our
      results suggested that EZH2 might be an independent prognostic factor for
      multiple survival measures in different cancers.

PMID- 25974090
TI  - One hundred twelve patients above 75 years old with tracheotomy: discharge
      delayed by 13 days: Our experience.

PMID- 25974091
TI  - Stress phase angle depicts differences in arterial stiffness: phantom and in vivo
      study.
AB  - The endothelial cells (ECs) lining of a blood vessel wall are exposed to both the
      wall shear stress (WSS) of blood flow and the circumferential strain (CS) of
      pulsing artery wall motion. Both WSS and CS keep involved in the modulation of
      ECs' biochemical response and function and the temporal phase angle between the
      two is called stress phase angle (SPA). Previous studies at the cellular level
      have indicated that SPA is highly negative at sites that are prone to
      atherosclerosis, and hypothesized that large SPA may contribute to atherogenesis.
      Till now, there is no experimental data to support this hypothesis, probably due
      to the lack of a proper tool for measuring WSS and CS simultaneously and real
      time. In this study, a non-invasive ultrasonic biomechanics method was utilized
      to quantitatively calculate the SPA and experimentally evaluate the role of SPA
      in predicting early atherosclerosis. Three silicon tubes with a stiffness of
      1.15, 3.62, 9.38 MPa were assembled in a pulsatile flow circuit and the values of
      SPA were measured to be -101.86 +/- 3.65 degrees ,-170.19 +/- 17.77 degrees  and 
      260.63 +/- 18.62 degrees , respectively. For the PVA-c phantoms, stiffness was
      162.45, 235.68 and 374.24 kPa, the SPA corresponding to -170.32 +/- 17.55 degrees
      ,-207.56 +/- 10.78 degrees  and -261.08 +/- 10.90 degrees , respectively. Both
      phantom studies results demonstrated that SPA was highly negative in stiffer
      arteries. Further, experiments were taken in healthy living rats as control group
      (n = 3), atherosclerotic model group (n = 3), and drug treated group (n = 3), and
      the results showed that SPA was most negative in the model group, and SPA was
      least negative in the control group. Together, this study suggested that highly
      negative SPA appeared to be a prominent mechanical feature of vessels prone to
      atherosclerotic disease.

PMID- 25974092
TI  - Management of Type 2 Diabetes Mellitus through Telemedicine.
AB  - BACKGROUND: Type 2 diabetes mellitus T2DM has a huge and growing burden on public
      health, whereas new care models are not implemented into clinical practice; in
      fact the purpose of this study was to test the effectiveness of a program of
      integrated care for T2DM, compared with ordinary diligence. METHODS: "Progetto
      Diabete Calabria" is a new organizational model for the management of patients
      with diabetes mellitus, based on General Practitioners (GPs) empowerment and the
      use of a web-based electronic health record, shared in remote consultations among
      GPs and Hospital Consultants. One-year change in glucose and main cardiovascular
      risk factors control in 104 patients (Cases) following this integrated care
      program has been evaluated and compared with that of 208 control patients
      (Controls) matched for age, gender, and cardiometabolic profile, and followed in
      an ordinary outpatient medical management by the Consultants only. Both patient
      groups had Day Hospitals before and after the study period. RESULTS: The mean
      number of accesses to the Consultants during the study was 0.6 +/- 0.9 for Cases,
      and 1.3 +/- 1.5 for Controls (p<0.0001). At follow-up, glycated hemoglobin
      (HbA1c) significantly decreased from 58 +/- 6 to 54 +/- 8 mmol/mol in Cases only
      (p=0.01); LDL cholesterol decreased in both groups; body mass index decreased in
      Cases only, from 31.0 +/- 4.8 to 30.5 +/- 4.6 kg/m(2) (p=0.03). CONCLUSIONS: The
      present study demonstrates that a health care program based on GPs empowerment
      and taking care plus remote consultation with Consultants is at least as
      effective as standard outpatient management, in order to improve the control of
      T2DM.

PMID- 25974094
TI  - Construction of Multifunctional 3-Amino-2-carbamimidoylacrylamides and Their
      Crystalline Channel-Type Inclusion Complexes.
AB  - 3-Amino-2-carbamimidoylacrylamides were efficiently prepared via a copper(I)
      catalyzed three-component reaction of sulfonylazides, propriolamides, and
      amidines. The synthesized compounds provided three kinds of crystalline
      structures based on the position of halogen. Two of them presented channel-type
      inclusion complexes with ethyl acetate through intermolecular hydrogen bonding,
      intermolecular C-H...pi and pi-pi interactions, and van der Waals forces. 

PMID- 25974093
TI  - Cost-effectiveness of clinical decision support system in improving maternal
      health care in Ghana.
AB  - OBJECTIVE: This paper investigated the cost-effectiveness of a computer-assisted
      Clinical Decision Support System (CDSS) in the identification of maternal
      complications in Ghana. METHODS: A cost-effectiveness analysis was performed in a
      before- and after-intervention study. Analysis was conducted from the provider's
      perspective. The intervention area was the Kassena- Nankana district where
      computer-assisted CDSS was used by midwives in maternal care in six selected
      health centres. Six selected health centers in the Builsa district served as the
      non-intervention group, where the normal Ghana Health Service activities were
      being carried out. RESULTS: Computer-assisted CDSS increased the detection of
      pregnancy complications during antenatal care (ANC) in the intervention health
      centres (before-intervention = 9 /1,000 ANC attendance; after-intervention =
      12/1,000 ANC attendance; P-value = 0.010). In the intervention health centres,
      there was a decrease in the number of complications during labour by 1.1%, though
      the difference was not statistically significant (before-intervention =107/1,000
      labour clients; after-intervention = 96/1,000 labour clients; P-value = 0.305).
      Also, at the intervention health centres, the average cost per pregnancy
      complication detected during ANC (cost -effectiveness ratio) decreased from
      US$17,017.58 (before-intervention) to US$15,207.5 (after-intervention).
      Incremental cost -effectiveness ratio (ICER) was estimated at US$1,142.
      Considering only additional costs (cost of computer-assisted CDSS), cost per
      pregnancy complication detected was US$285. CONCLUSIONS: Computer -assisted CDSS
      has the potential to identify complications during pregnancy and marginal
      reduction in labour complications. Implementing computer-assisted CDSS is more
      costly but more effective in the detection of pregnancy complications compared to
      routine maternal care, hence making the decision to implement CDSS very complex.
      Policy makers should however be guided by whether the additional benefit is worth
      the additional cost.

PMID- 25974095
TI  - Preparation of compact biocompatible quantum dots using multicoordinating
      molecular-scale ligands based on a zwitterionic hydrophilic motif and lipoic acid
      anchors.
AB  - Luminescent quantum dots (QDs) can potentially be used for many biological
      experiments, provided that they are constructed in such a way as to be stable in
      biological matrices. Furthermore, QDs that are compact in size and easy to couple
      to biomolecules can be readily used for applications ranging from protein
      tracking to vasculature imaging. In this protocol, we describe the preparation of
      ligands comprising either one or two lipoic acid (LA) groups chemically linked to
      a zwitterion moiety. These ligands are then used to functionalize luminescent QDs
      via a photochemical transformation of LA. This route produces nanocrystals that
      are compact in size and stable over a broad range of conditions. In addition, the
      resulting QDs are readily self-assembled with polyhistidine-appended proteins.
      This mode of conjugation maintains the protein biological activity and its
      orientation, yielding highly promising fluorescent conjugates that can be used
      for imaging and sensing. The protocol in its entirety can be completed in 3
      weeks. 

PMID- 25974096
TI  - Inexpensive, rapid prototyping of microfluidic devices using overhead
      transparencies and a laser print, cut and laminate fabrication method.
AB  - We describe a technique for fabricating microfluidic devices with complex
      multilayer architectures using a laser printer, a CO2 laser cutter, an office
      laminator and common overhead transparencies as a printable substrate via a laser
      print, cut and laminate (PCL) methodology. The printer toner serves three
      functions: (i) it defines the microfluidic architecture, which is printed on the
      overhead transparencies; (ii) it acts as the adhesive agent for the bonding of
      multiple transparency layers; and (iii) it provides, in its unmodified state,
      printable, hydrophobic 'valves' for fluidic flow control. By using common
      graphics software, e.g., CorelDRAW or AutoCAD, the protocol produces microfluidic
      devices with a design-to-device time of ~40 min. Devices of any shape can be
      generated for an array of multistep assays, with colorimetric detection of
      molecular species ranging from small molecules to proteins. Channels with varying
      depths can be formed using multiple transparency layers in which a CO2 laser is
      used to remove the polyester from the channel sections of the internal layers.
      The simplicity of the protocol, availability of the equipment and substrate and
      cost-effective nature of the process make microfluidic devices available to those
      who might benefit most from expedited, microscale chemistry. 

PMID- 25974097
TI  - Myeloid translocation gene-16 co-repressor promotes degradation of hypoxia
      inducible factor 1.
AB  - The myeloid translocation gene 16 (MTG16) co-repressor down regulates expression
      of multiple glycolytic genes, which are targets of the hypoxia-inducible factor 1
      (HIF1) heterodimer transcription factor that is composed of oxygen-regulated
      labile HIF1alpha and stable HIF1beta subunits. For this reason, we investigated
      whether MTG16 might regulate HIF1 negatively contributing to inhibition of
      glycolysis and stimulation of mitochondrial respiration. A doxycycline Tet-On
      system was used to control levels of MTG16 in B-lymphoblastic Raji cells. Results
      from co-association studies revealed MTG16 to interact with HIF1alpha. The co
      association required intact N-terminal MTG16 residues including Nervy Homology
      Region 1 (NHR1). Furthermore, electrophoretic mobility shift assays demonstrated
      an association of MTG16 with hypoxia response elements (HREs) in PFKFB3, PFKFB4
      and PDK1 promoters in-vitro. Results from chromatin immunoprecipitation assays
      revealed co-occupancy of these and other glycolytic gene promoters by HIF1alpha,
      HIF1beta and MTG16 in agreement with possible involvement of these proteins in
      regulation of glycolytic target genes. In addition, MTG16 interacted with prolyl
      hydroxylase D2 and promoted ubiquitination and proteasomal degradation of
      HIF1alpha. Our findings broaden the area of MTG co-repressor functions and reveal
      MTG16 to be part of a protein complex that controls the levels of HIF1alpha. 

PMID- 25974098
TI  - In-situ investigation of stress conditions during expansion of bare metal stents
      and PLLA-coated stents using the XRD sin(2)psi-technique.
AB  - Drug eluting stents (DES) consist of platform, coating and drug. The platform
      often is a balloon-expandable bare metal stent made of the CoCr alloy L-605 or
      stainless steel 316 L. The function of the coating, typically a permanent
      polymer, is to hold and release the drug, which should improve therapeutic
      outcome. Before implantation, DES are compressed (crimped) to allow implantation
      in the human body. During implantation, DES are expanded by balloon inflation.
      Crimping, as well as expansion, causes high stresses and high strains locally in
      the DES struts, as well as in the polymer coating. These stresses and strains are
      important design criteria of DES. Usually, they are calculated numerically by
      finite element analysis (FEA), but experimental results for validation are hardly
      available. In this work, the X-ray diffraction (XRD) sin(2)psi-technique is
      applied to in-situ determination of stress conditions of bare metal L-605 stents,
      and Poly-(L-lactide) (PLLA) coated stents. This provides a realistic
      characterization of the near-surface stress state and a validation option of the
      numerical FEA. XRD-results from terminal stent struts of the bare metal stent
      show an increasing compressive load stress in tangential direction with
      increasing stent expansion. These findings correlate with numerical FEA results.
      The PLLA-coating also bears increasing compressive load stress during expansion.

PMID- 25974099
TI  - Predictive model of the prostate motion in the context of radiotherapy: A
      biomechanical approach relying on urodynamic data and mechanical testing.
AB  - In this paper, a biomechanical approach relying on urodynamic data and mechanical
      tests is proposed for an accurate prediction of the motion of the pelvic organs
      in the context of the prostate radiotherapy. As a first step, an experimental
      protocol is elaborated to characterize the mechanical properties of the bladder
      and rectum wall tissues; uniaxial tensile tests are performed on porcine
      substrates. In a second step, the parameters of Ogden-type hyperelastic
      constitutive models are identified; their relevance in the context of the
      implementation of a human biomechanical model is verified by means of preliminary
      Finite Elements (FE) simulations against human urodynamic data. In a third step,
      the identified constitutive equations are employed for the simulations of the
      motion and interactions of the pelvic organs due to concomitant changes of the
      distension volumes of the urinary bladder and rectum. The effectiveness of the
      developed biomechanical model is demonstrated in investigating the motion of the
      bladder, rectum and prostate organs; the results in terms of displacements are
      shown to be in good agreement with measurements inherent to a deceased person,
      with a relative error close to 6%. 

PMID- 25974100
TI  - Rosetta comparative modeling for library design: Engineering alternative inducer
      specificity in a transcription factor.
AB  - Structure-based rational mutagenesis for engineering protein functionality has
      been limited by the scarcity and difficulty of obtaining crystal structures of
      desired proteins. On the other hand, when high-throughput selection is possible,
      directed evolution-based approaches for gaining protein functionalities have been
      random and fortuitous with limited rationalization. We combine comparative
      modeling of dimer structures, ab initio loop reconstruction, and ligand docking
      to select positions for mutagenesis to create a library focused on the ligand
      contacting residues. The rationally reduced library requirement enabled
      conservative control of the substitutions by oligonucleotide synthesis and
      bounding its size within practical transformation efficiencies (~ 10(7)
      variants). This rational approach was successfully applied on an inducer-binding
      domain of an Acinetobacter transcription factor (TF), pobR, which shows high
      specificity for natural effector molecule, 4-hydroxy benzoate (4HB), but no
      native response to 3,4-dihydroxy benzoate (34DHB). Selection for mutants with
      high transcriptional induction by 34DHB was carried out at the single-cell level
      under flow cytometry (via green fluorescent protein expression under the control
      of pobR promoter). Critically, this selection protocol allows both selection for
      induction and rejection of constitutively active mutants. In addition to gain-of
      function for 34DHB induction, the selected mutants also showed enhanced
      sensitivity and response for 4HB (native inducer) while no sensitivity was
      observed for a non-targeted but chemically similar molecule, 2-hydroxy benzoate
      (2HB). This is unique application of the Rosetta modeling protocols for library
      design to engineer a TF. Our approach extends applicability of the Rosetta
      redesign protocol into regimes without a priori precision structural information.

PMID- 25974101
TI  - The effect of insulin to decrease neointimal growth after arterial injury is
      endothelial nitric oxide synthase-dependent.
AB  - In vitro, insulin has mitogenic effects on vascular smooth muscle cells (VSMC)
      but also has protective effects on endothelial cells by stimulating nitric oxide
      (NO) production and endothelial nitric oxide synthase (eNOS) expression.
      Furthermore, NOS inhibition attenuates the effect of insulin to inhibit VSMC
      migration in vitro. Using an in vivo model, we have previously shown that insulin
      decreases neointimal growth and cell migration and increases re
      endothelialization after arterial injury in normal rats. Since insulin can
      stimulate NOS, and NO can decrease neointimal growth, we hypothesized that NOS,
      and more specifically eNOS was required for the effects of insulin in vivo. Rats
      were given subcutaneous insulin implants (3 U/day) alone or with the NOS
      inhibitor l-NAME (2 mg kg(-1) day(-1)) 3 days before arterial (carotid or aortic)
      balloon catheter injury. Insulin decreased both neointimal area (P < 0.01) and
      cell migration (P < 0.01), and increased re-endothelialization (P < 0.05). All of
      these effects were prevented by the co-administration of l-NAME. Insulin was
      found to decrease inducible NOS expression (P < 0.05) but increase eNOS
      phosphorylation (P < 0.05). These changes were also translated at the functional
      level where insulin improved endothelial-dependent vasorelaxation. To further
      study the NOS isoform involved in insulin action, s.c. insulin (0.1 U/day) was
      given to wild-type and eNOS knockout mice. We found that insulin was effective at
      decreasing neointimal formation in wild-type mice after wire injury of the
      femoral artery, whereas this effect of insulin was absent in eNOS knockout mice.
      These results show that the vasculoprotective effect of insulin after arterial
      injury is mediated by an eNOS-dependent mechanism. 

PMID- 25974102
TI  - The potential role of DNA methylation in the pathogenesis of abdominal aortic
      aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is characterised by the chronic degradation and
      gradual, irreversible dilation of the abdominal aorta. Smoking, genetics, male
      sex and increased age are major factors associated with developing AAA. Rupture
      contributes to around 2% of deaths in all Caucasians over 65, and there is no
      pharmaco-therapeutic treatment. Methylation is an epigenetic modification to DNA,
      where a methyl group is added to a cytosine base 5' to a guanine (CpG
      dinucleotide). Methylation patterns are long term, inherited signatures that can
      induce changes in gene transcription, and can be affected by both genetic and
      environmental factors. Methylation changes are involved in hypertension and
      atherosclerosis, both of which are risk factors of, and often coexist with AAA.
      Extra-cellular matrix degradation and inflammation, both important pathological
      hallmarks of AAA, are also promoted by changes in CpG methylation in other
      diseases. Additionally, the adverse effects of smoking and ageing take place
      largely through epigenetic manipulation of the genome. Every factor associated
      with AAA appears to be associated with DNA methylation, yet no direct evidence
      confirms this. Future work to identify a link between global methylation and AAA,
      and differentially methylated regions may reveal valuable insight. The
      identification of a common epigenetic switching process may also signify a
      promising future for AAA pharmaco-therapeutic strategies. Epigenetic therapies
      are being designed to target pathogenic CpG methylation changes in other
      diseases, and it is feasible that these therapies may also be applicable to AAA
      in the future. 

PMID- 25974103
TI  - Seven common mistakes in population genetics and how to avoid them.
AB  - As the data resulting from modern genotyping tools are astoundingly complex,
      genotyping studies require great care in the sampling design, genotyping, data
      analysis and interpretation. Such care is necessary because, with data sets
      containing thousands of loci, small biases can easily become strongly significant
      patterns. Such biases may already be present in routine tasks that are present in
      almost every genotyping study. Here, I discuss seven common mistakes that can be
      frequently encountered in the genotyping literature: (i) giving more attention to
      genotyping than to sampling, (ii) failing to perform or report experimental
      randomization in the laboratory, (iii) equating geopolitical borders with
      biological borders, (iv) testing significance of clustering output, (v)
      misinterpreting Mantel's r statistic, (vi) only interpreting a single value of k
      and (vii) forgetting that only a small portion of the genome will be associated
      with climate. For every of those issues, I give some suggestions how to avoid the
      mistake. Overall, I argue that genotyping studies would benefit from establishing
      a more rigorous experimental design, involving proper sampling design,
      randomization and better distinction of a priori hypotheses and exploratory
      analyses. 

PMID- 25974105
TI  - Metastatic synovial sarcoma of the scalp: Case report.
AB  - BACKGROUND: Synovial sarcoma is a malignant tumor of soft tissue that is rarely
      found in the head and neck. Even less common are metastasis within the head and
      neck. METHODS: We describe a case of a delayed metastatic synovial sarcoma to the
      scalp. A man who had been diagnosed and treated 16 years previously for
      monophasic synovial sarcoma of the groin, presented with a new scalp lesion
      confirmed to be metastatic monophasic synovial sarcoma. Wide local excision and
      sentinel lymph node biopsy (SLNB) were performed and adjuvant radiation therapy
      was deferred. RESULTS: A positron emission tomography (PET)/CT was obtained 3
      months after surgery and showed no evidence of local recurrence or metastatic
      disease. CONCLUSION: This case report describes a rare case of synovial sarcoma
      metastasizing to the scalp. The genetic, histopathologic, and clinical features
      of synovial sarcoma are reviewed with a focus on their manifestation and
      management within the head and neck.

PMID- 25974104
TI  - Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory
      Hyperalgesia in Mouse Dorsal Root Ganglion Neurons.
AB  - The Cav3.2 isoform of the T-type calcium channel is expressed in primary sensory
      neurons of the dorsal root ganglion (DRG), and these channels contribute to
      nociceptive and neuropathic pain in rats. However, there are conflicting reports
      on the roles of these channels in pain processing in rats and mice. In addition,
      the function of T-type channels in persistent inflammatory hyperalgesia is poorly
      understood. We performed behavioral and comprehensive histochemical analyses to
      characterize Cav3.2-expressing DRG neurons and examined the regulation of T-type
      channels in DRGs from C57BL/6 mice with carrageenan-induced inflammatory
      hyperalgesia. We show that approximately 20% of mouse DRG neurons express Cav3.2
      mRNA and protein. The size of the majority of Cav3.2-positive DRG neurons (69 +/-
      8%) ranged from 300 to 700 MUm2 in cross-sectional area and 20 to 30 MUm in
      estimated diameter. These channels co-localized with either neurofilament-H (NF
      H) or peripherin. The peripherin-positive cells also overlapped with neurons that
      were positive for isolectin B4 (IB4) and calcitonin gene-related peptide (CGRP)
      but were distinct from transient receptor potential vanilloid 1 (TRPV1)-positive
      neurons during normal mouse states. In mice with carrageenan-induced inflammatory
      hyperalgesia, Cav3.2 channels, but not Cav3.1 or Cav3.3 channels, were
      upregulated in ipsilateral DRG neurons during the sub-acute phase. The increased
      Cav3.2 expression partially resulted from an increased number of Cav3.2
      immunoreactive neurons; this increase in number was particularly significant for
      TRPV1-positive neurons. Finally, preceding and periodic intraplantar treatment
      with the T-type calcium channel blockers mibefradil and NNC 55-0396 markedly
      reduced and reversed mechanical hyperalgesia during the acute and sub-acute
      phases, respectively, in mice. These data suggest that Cav3.2 T-type channels
      participate in the development of inflammatory hyperalgesia, and this channel
      might play an even greater role in the sub-acute phase of inflammatory pain due
      to increased co-localization with TRPV1 receptors compared with that in the
      normal state. 

PMID- 25974106
TI  - Glycated albumin is a more accurate glycaemic indicator than haemoglobin A1c in
      diabetic patients with pre-dialysis chronic kidney disease.
AB  - AIM: Glycated albumin (GA) has been reported to be a more reliable glycaemic
      indicator than haemoglobin A1c (HbA1c ) in patients with diabetes on dialysis.
      However, the significance of these assays has been less evaluated in patients
      with diabetes and pre-dialysis chronic kidney disease (CKD). METHODS: GA, HbA1c
      and fasting serum glucose were measured simultaneously in 146 patients with
      diabetes. Based on estimated glomerular filtration rate (eGFR), the subjects were
      categorized into a pre-dialysis CKD group (eGFR < 60 mL/min per 1.73 m2 , n = 97)
      and a non-CKD group (eGFR >= 60 mL/min per 1.73 m2 , n = 49). RESULTS: The
      glucose/HbA1c and GA/HbA1c ratios were significantly higher in the CKD group than
      those in the non-CKD group. The glucose/GA ratio did not differ significantly
      between the two groups. In the pre-dialysis CKD group, eGFR was negatively
      correlated with the glucose/HbA1c ratio (r = -0.343, P = 0.001) and the GA/HbA1c
      ratio (r = -0.499, P < 0.001). However, no significant correlation was detected
      between eGFR and the glucose/GA ratio. In the non-CKD group, eGFR was not
      correlated with the glucose/HbA1c ratio, the glucose/GA ratio, or the GA/HbA1c
      ratio. A multivariate regression analysis showed that eGFR had a significant
      impact on HbA1c but no effect on GA in the pre-dialysis CKD group (beta = 0.210,
      P = 0.005). In the non-CKD group, eGFR did not affect HbA1c or GA. CONCLUSION:
      Our results show that HbA1c significantly underestimated glycaemic control,
      whereas GA more accurately reflected glycaemic control in diabetic patients with
      pre-dialysis CKD.

PMID- 25974107
TI  - Endogenous minerals have influences on surface electrochemistry and ion exchange
      properties of biochar.
AB  - The feedstocks for biochar production are diverse and many of them contain
      various minerals in addition to being rich in carbon. Twelve types of biomass
      classified into 2 categories: plant-based and municipal waste, were employed to
      produce biochars under 350  degrees C and 500  degrees C. Their pH, point of zero
      net charge (PZNC), zeta potential, cation and anion exchange capacity (CEC and
      AEC) were analyzed. The municipal waste-based biochars (MW-BC) had higher mineral
      levels than the plant-based biochars (PB-BC). However, the water soluble mineral
      levels were lower in the MW-BCs due to the dominant presence of less soluble
      minerals, such as CaCO3 and (Ca,Mg)3(PO4)2. The higher total minerals in MW-BCs
      accounted for the higher PZNC (5.47-9.95) than in PB-BCs (1.91-8.18), though the
      PZNCs of the PB-BCs increased more than that of the MW-BCs as the production
      temperature rose. The minerals had influence on the zeta potentials via affecting
      the negative charges of biochars and the ionic strength of solution. The organic
      functional groups in PB-BCs such as -COOH and -OH had a greater effect on the CEC
      and AEC, while the minerals had a greater effect on that of MW-BCs. The measured
      CEC and AEC values had a strong positive correlation with the total amount of
      soluble cations and anions, respectively. Results indicated that biochar surface
      charges depend not only on the organic functional groups, but also on the
      minerals present and to some extent, minerals have more influences on the surface
      electrochemistry and ion exchange properties of biochar.

PMID- 25974108
TI  - Bilateral Choroidopathy and Serous Retinal Detachments During Ipilimumab
      Treatment for Cutaneous Melanoma.

PMID- 25974109
TI  - Antimicrobial Air Filters Using Natural Euscaphis japonica Nanoparticles.
AB  - Controlling bioaerosols has become more important with increasing participation
      in indoor activities. Treatments using natural-product nanomaterials are a
      promising technique because of their relatively low toxicity compared to
      inorganic nanomaterials such as silver nanoparticles or carbon nanotubes. In this
      study, antimicrobial filters were fabricated from natural Euscaphis japonica
      nanoparticles, which were produced by nebulizing E. japonica extract. The coated
      filters were assessed in terms of pressure drop, antimicrobial activity,
      filtration efficiency, major chemical components, and cytotoxicity. Pressure drop
      and antimicrobial activity increased as a function of nanoparticle deposition
      time (590, 855, and 1150 ug/cm2(filter) at 3-, 6-, and 9-min depositions,
      respectively). In filter tests, the antimicrobial efficacy was greater against
      Staphylococcus epidermidis than Micrococcus luteus; ~61, ~73, and ~82% of M.
      luteus cells were inactivated on filters that had been coated for 3, 6, and 9
      min, respectively, while the corresponding values were ~78, ~88, and ~94% with S.
      epidermidis. Although statistically significant differences in filtration
      performance were not observed between samples as a function of deposition time,
      the average filtration efficacy was slightly higher for S. epidermidis aerosols
      (~97%) than for M. luteus aerosols (~95%). High-performance liquid chromatography
      (HPLC) and electrospray ionization-tandem mass spectrometry (ESI/MS) analyses
      confirmed that the major chemical compounds in the E. japonica extract were
      1(beta)-O-galloyl pedunculagin, quercetin-3-O-glucuronide, and kaempferol-3-O
      glucoside. In vitro cytotoxicity and disk diffusion tests showed that E. japonica
      nanoparticles were less toxic and exhibited stronger antimicrobial activity
      toward some bacterial strains than a reference soluble nickel compound, which is
      classified as a human carcinogen. This study provides valuable information for
      the development of a bioaerosol control system that is environmental friendly and
      suitable for use in indoor environments.

PMID- 25974110
TI  - The expression of CD30 based on immunohistochemistry predicts inferior outcome in
      patients with diffuse large B-cell lymphoma.
AB  - The prognostic value of CD30 expression in diffuse large B-cell lymphoma
      (DLBCL)remains controversial. Herein, we performed this retrospective study to
      investigate the clinical and prognostic significance of CD30 expression in
      patients with DLBCL.Among all the 146 patients, the expression of CD30 was
      observed in 23 cases (15.7%).The DLBCL patients with CD30 expression showed more
      likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell
      like (Non-GCB) DLBCL, BCL-2 and Ki-67 overexpression (p<0.05). Patients with CD30
      expression showed significantly poor overall and event-free survival compared
      with CD30 negative patients(p = 0.031 and 0.041, respectively), especially those
      with the high intermediate/high-risk international prognostic index (IPI)(p =
      0.001 and 0.007, respectively). The prognostic value of CD30 expression retained
      in DLBCL patients treated with either CHOP (cyclophosphamide, doxorubicin,
      vincristine,prednisone) or R-CHOP(rituximab+CHOP). The multivariate analysis
      revealed that the expression of CD30 remained an unfavorable factor for both
      overall and event-free survival (p = 0.001 and 0.002, respectively). In
      conclusion, these data suggest that CD30 is expressed predominantly in Non
      GCBDLBCL. The expression of CD30 implied poor outcome in DLBCL patients treated
      with either CHOP or R-CHOP, especially those with the high intermediate/high-risk
      IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical
      interest.

PMID- 25974112
TI  - On the cause of conductivity degradation in sodium strontium silicate ionic
      conductor.
AB  - Here we present strong experimental evidence that elucidates the fundamental
      cause for the conductivity degradation observed in Na-SrSiO3 ionic conductor. 

PMID- 25974111
TI  - Mass Mortality Events in the NW Adriatic Sea: Phase Shift from Slow- to Fast
      Growing Organisms.
AB  - Massive outbreaks are increasing all over the world, which are likely related to
      climate change. The North Adriatic Sea, a sub-basin of the Mediterranean Sea, is
      a shallow semi-closed sea receiving high nutrients inputs from important rivers.
      These inputs sustain the highest productive basin of the Mediterranean Sea.
      Moreover, this area shows a high number of endemisms probably due to the high
      diversity of environmental conditions and the conspicuous food availability.
      Here, we documented two massive mortalities (2009 and 2011) and the pattern of
      recovery of the affected biocoenoses in the next two years. Results show an
      impressive and fast shift of the benthic assemblage from a biocoenosis mainly
      composed of slow-growing and long-lived species to a biocoenosis dominated by
      fast-growing and short-lived species. The sponge Chondrosia reniformis, one of
      the key species of this assemblage, which had never been involved in previous
      massive mortality events in the Mediterranean Sea, reduced its coverage by 70%,
      and only few small specimens survived. All the damaged sponges, together with
      many associated organisms, were detached by rough-sea conditions, leaving large
      bare areas on the rocky wall. Almost three years after the disease, the survived
      specimens of C. reniformis did not increase significantly in size, while the bare
      areas were colonized by fast-growing species such as stoloniferans, hydrozoans,
      mussels, algae, serpulids and bryozoans. Cnidarians were more resilient than
      massive sponges since they quickly recovered in less than one month. In the study
      area, the last two outbreaks caused a reduction in the filtration efficiency of
      the local benthic assemblage by over 60%. The analysis of the times series of
      wave heights and temperature revealed that the conditions in summer 2011 were not
      so extreme as to justify severe mass mortality, suggesting the occurrence of
      other factors which triggered the disease. The long-term observations of a
      benthic assemblage in the NW Adriatic Sea allowed us to monitor its dynamics
      before, during and after the mortality event. The N Adriatic Sea responds quickly
      to climatic anomalies and other environmental stresses because of the reduced
      dimension of the basin. The long-term consequences of frequent mass mortality
      episodes in this area could promote the shift from biocoenoses dominated by slow
      growing and long-lived species to assemblages dominated by plastic and short life
      cycle species. 

PMID- 25974113
TI  - Structure and Properties of Polyfluoride Fn(-) Clusters (n = 3-29).
AB  - The electronic and geometrical structures of the neutral Fn and singly negatively
      charged Fn(-) polyfluorides (n = 3-29) are studied using three levels of theory:
      density functional theory (DFT) with generalized gradient approximation, hybrid
      Hartree-Fock-DFT, and hybrid HF-DFT with long-range corrections. For n > 4, each
      polyfluoride possesses a number of states with different geometries that are
      closely spaced in total energy. The geometrical structures of the lowest total
      energy states follow different patterns for the even-n and odd-n Fn(-) anion
      branches with a preference for higher symmetry geometries. The largest F29(-)
      anion considered is found to possess Oh symmetry. All the anions beginning with
      F3(-) are found to possess adiabatic and vertical electron detachment energies
      exceeding the electron affinities of halogen atoms and are therefore superhalogen
      anions. Electron affinities, energies of formation, and binding energies show
      oscillatory behavior as functions of the number n of fluorine atoms. The neutral
      Fn species are found to be barely stable and are bound by polarization forces.
      The Fn(-) anions, on the contrary, are quite stable toward the loss of F, F(-),
      and F2(-), but not to the loss of F2. 

PMID- 25974114
TI  - Metabolite profile of the tomato dwarf cultivar Micro-Tom and comparative
      response to saline and nutritional stresses with regard to a commercial cultivar.
AB  - BACKGROUND: The dwarf tomato variety Micro-Tom has been used as a plant model for
      studies of plant development. However, its response to environmental and
      agricultural factors has not been well studied. This work studies the
      phytochemical content of Micro-Tom tomato and its comparative response to saline
      and nutritional (N, K and Ca) stresses with regard to a commercial variety.
      RESULTS: The chromatographic profiles of Micro-Tom were similar to those of the
      commercial variety and the only differences appear to be the concentration of the
      components. In Micro-Tom, the concentrations of sugars and organic acids
      increased by salinity in a lesser extent than in Optima. Moreover, contrary to
      that observed in the commercial variety, phenolic compounds and vitamin C did not
      increase by salinity in the dwarf variety. However, both varieties increased
      similarly the concentrations of carotenoids under saline conditions. Finally,
      fruit yield and most primary and secondary metabolite concentrations in Micro-Tom
      were not affected by N, K or Ca limitation. CONCLUSIONS: The mutations leading to
      the dwarf phenotype did not greatly alter the metabolite profiles but studies
      using Micro-Tom as a plant model should consider the lower capacity for sugars
      and organic acids under saline conditions and the greater tolerance to nutrient
      limitation of the dwarf variety.

PMID- 25974115
TI  - Genotype-dependent differences in age of manifestation and arrhythmia
      complications in short QT syndrome.
AB  - BACKGROUND: Short QT syndrome (SQTS) is a rare inheritable arrhythmia, associated
      with atrial and ventricular fibrillations, caused by mutations in six cardiac ion
      channel genes with high penetrance. However, genotype-specific clinical
      differences between SQTS patients remain to be elucidated. METHODS AND RESULTS:
      We screened five unrelated Japanese SQTS families, and identified three mutations
      in KCNH2 and KCNQ1. A novel mutation KCNH2-I560T, when expressed in COS-7 cells,
      showed a 2.5-fold increase in peak current density, and a positive shift (+14 mV)
      of the inactivation curve compared with wild type. Computer simulations
      recapitulated the action potential shortening and created an arrhythmogenic
      substrate for ventricular fibrillation. In another family carrying the mutation
      KCNQ1-V141M, affected members showed earlier onset of manifestation and frequent
      complications of bradyarrhythmia. To determine genotype-specific phenotypes in
      SQT1 (KCNH2), SQT2 (KCNQ1), and other subtypes SQT3-6, we analyzed clinical
      variables in 65 mutation-positive patients among all the 132 SQTS cases
      previously reported. The age of manifestation was significantly later in SQT1
      (SQT1: 35 +/- 19 years, n = 30; SQT2: 17 +/- 25 years, n = 8, SQT3-6: 19 +/- 15
      years, n = 15; p = 0.011). SQT2 exhibited a higher prevalence of bradyarrhythmia
      (SQT2: 6/8, 75%; non-SQT2: 5/57, 9%; p < 0.001) and atrial fibrillation (SQT2:
      5/8, 63%; non-SQT2: 12/57, 21%; p = 0.012). Of 51 mutation-positive individuals
      from 16 SQTS families, nine did not manifest short QT, but exhibited other ECG
      abnormalities such as atrial fibrillation. The resulting penetrance, 82%, was
      lower than previously recognized. CONCLUSION: We propose that SQTS patients may
      exhibit different clinical manifestations depending upon their genotype.

PMID- 25974116
TI  - Versatile Synthesis of Stable, Functional Polypeptides via Reaction with
      Epoxides.
AB  - Methodology was developed for efficient alkylation of methionine residues using
      epoxides as a general strategy to introduce a wide range of functional groups
      onto polypeptides. Use of a spacer between epoxide and functional groups further
      allowed addition of sterically demanding functionalities. Contrary to other
      methods to alkylate methionine residues, epoxide alkylations allow the reactions
      to be conducted in wet protic media and give sulfonium products that are stable
      against dealkylation. These functionalizations are notable since they are
      chemoselective, utilize stable and readily available epoxides, and allow facile
      incorporation of an unprecedented range of functional groups onto simple
      polypeptides using stable linkages. 

PMID- 25974117
TI  - Tracheostoma reconstruction with the supraclavicular artery island flap.
AB  - Tracheostoma wounds are complex defects that commonly occur in patients with
      vessel-depleted necks after cervical lymphadenectomy, who have multiple medical
      comorbidities, and a history of radiation therapy. The authors report
      reconstruction of 5 tracheostoma wounds using a pedicled, supraclavicular artery
      island flap as a reconstructive alternative. There were no flap losses, fistulas
      or leaks, revisions, or other complications. The supraclavicular artery island
      flap is a versatile, reliable, and effective option for tracheostoma
      reconstruction.

PMID- 25974118
TI  - Herpes zoster in a free transverse rectus abdominis myocutaneous flap after
      delayed breast reconstruction: evidence of spontaneous reinnervation.
AB  - In concert with advances in surgical reconstruction techniques and improved
      survival after breast cancer, both the aesthetic and functional outcomes,
      especially sensory recovery, of breast reconstruction have been addressed. Most
      studies on sensory recovery in reconstructed breasts have utilized patients'
      subjective responses to touch, pain, temperature, and pressure. In contrast, this
      report describes a case of herpes zoster that developed in a free transverse
      rectus abdominis myocutaneous flap, which provides objective evidence of
      spontaneous reinnervation after breast reconstruction.

PMID- 25974120
TI  - A Case Report of an Infant With Arthrogryposis.
AB  - PURPOSE: This case report documents limitations of body structures and function,
      activity, and participation for an infant with arthrogryposis multiplex congenita
      and reports frequency and timing of interventions for this child. SUMMARY OF KEY
      POINTS: The infant was followed from 11 days to 9 months of age while receiving
      occupational therapy and physical therapy on alternating weeks, with orthopedic
      visits for lower extremity serial casting. Passive range of motion improved and
      pain scores decreased during passive range of motion. The Patient Specific
      Functional Scale score increased; The Peabody Developmental Motor Scales, 2nd
      edition, standard score decreased from 9 in locomotion and stationary skills to 3
      in locomotion and 8 in stationary skills. RECOMMENDATIONS FOR CLINICAL PRACTICE:
      Outcomes demonstrate improvement in impairments of body structures and functions,
      participation, and some activities, through a program of stretching,
      strengthening, splinting, casting, and bilateral Achilles tenotomies for this
      infant with arthrogryposis multiplex congenita.

PMID- 25974119
TI  - Daily Intervention for Young Children With Cerebral Palsy in GMFCS Level V: A
      Case Series.
AB  - PURPOSE: To describe a daily physical therapy (PT) intervention program and
      outcomes for 2 young children with spastic quadriplegia, Gross Motor Function
      Classification System (GMFCS) level V, and to evaluate the feasibility of using a
      daily program in an urban children's hospital outpatient setting. SUMMARY OF KEY
      POINTS: Two young children, GMFCS level V, received 2 hours of PT intervention
      based on motor learning principles 5 days a week for 4 consecutive weeks. Gross
      Motor Functional Measure (GMFM-66, GMFM-88) and the Bayley Scales of Infant
      Development, Third Edition, were used as pre- and postoutcome measures. The
      daily, high intensity intervention was well tolerated. Improvements in motor
      function, language, and cognitive skills were found. STATEMENT OF CONCLUSION: A
      daily PT program appears feasible and may improve overall development in young
      children with cerebral palsy in GMFCS level V.

PMID- 25974121
TI  - Management of an Anterior Cruciate Ligament Tear in a 5 Year-Old Boy.
AB  - PURPOSE: The purpose of this retrospective case report was to describe clinical
      decision making during the examination and treatment of a 5-year-old boy with an
      anterior cruciate ligament (ACL) tear. KEY POINTS: A paucity of research exists
      for the management of ACL tears in children. A combination of manual therapy
      interventions initially, followed by a unique and comprehensive therapeutic
      exercise program, was implemented during the course of a 3-month treatment
      period. Improvements in range of motion, quadriceps strength, single-leg stance
      time, and the Knee Injury and Osteoarthritis Outcome Score were noted. At
      discharge, the patient safely returned to unrestricted home and school
      activities. CONCLUSION: This case demonstrates successful management of a child
      after an ACL injury. CLINICAL IMPLICATIONS: Clinicians are encouraged to
      implement sound clinical reasoning in the absence of well-established evidence
      when treating similar patients in their clinical practice.

PMID- 25974122
TI  - Immediate Loading of Edentulous Mandible With Prefabricated Bars: A Long-Term
      Study of 7 Years.
AB  - PURPOSE: To present clinical data from a 7-year follow-up study of edentulous
      mandibles rehabilitated according to an immediate loading protocol with
      prefabricated bars. MATERIALS AND METHODS: Forty-four implants were inserted in
      11 patients and were evaluated by means of resonance frequency analysis (RFA) and
      clinical and radiographic examination. RESULTS: Ten patients returned for the 7
      year evaluation and presented no implant loss. The stability measurements were
      performed immediately after implant placement (T0 = 64.5 +/- 6.6 ISQ) and 1 year
      (T1 = mean 66.8 +/- 4.2 ISQ), and 7 years (T7 = mean 62.8 +/- 5.4) after being in
      function. The analysis of the RFA values showed a statistically significant
      decrease in implant stability after 7 years in function, although the final
      values are considered adequate for treatment success. Panoramic x-ray examination
      showed bone loss greater than the first thread in 10 implants. CONCLUSION:
      According to the obtained data, it can be concluded that immediate loading
      according to this protocol with prefabricated bars is a valid treatment option
      for edentulous patients providing sufficient long-term success.

PMID- 25974123
TI  - To the editor.

PMID- 25974124
TI  - In response.

PMID- 25974125
TI  - Low-Cost, Disposable, Flexible and Highly Reproducible Screen Printed SERS
      Substrates for the Detection of Various Chemicals.
AB  - Ideal SERS substrates for sensing applications should exhibit strong signal
      enhancement, generate a reproducible and uniform response, and should be able to
      fabricate in large-scale and low-cost. Herein, we demonstrate low-cost, highly
      sensitive, disposable and reproducible SERS substrates by means of screen
      printing Ag nanoparticles (NPs) on a plastic PET (Polyethylene terephthalate)
      substrates. While there are many complex methods for the fabrication of SERS
      substrates, screen printing is suitable for large-area fabrication and overcomes
      the uneven radial distribution. Using as-printed Ag substrates as the SERS
      platform, detection of various commonly known chemicals have been done. The SERS
      detection limit of Rhodamine 6G (R6G) is higher than the concentration of 1 * 10(
      10) M. The relative standard deviation (RSD) value for 784 points on the
      detection of R6G and Malachite green (MG) is less than 20% revealing a
      homogeneous SERS distribution and high reproducibility. Moreover, melamine (MA)
      is detected in fresh liquid-milk without additional pretreatment, which may
      accelerate the application of rapid on-line detection of MA in liquid milk. Our
      screen printing method highlights the use of large-scale printing strategies for
      the fabrication of well-defined functional nanostructures with applications well
      beyond the field of SERS sensing. 

PMID- 25974127
TI  - Compact tomato seedlings and plants upon overexpression of a tomato chromatin
      remodelling ATPase gene.
AB  - Control of plant growth is an important aspect of crop productivity and yield in
      agriculture. Overexpression of the AtCHR12/23 genes in Arabidopsis thaliana
      reduced growth habit without other morphological changes. These two genes encode
      Snf2 chromatin remodelling ATPases. Here, we translate this approach to the
      horticultural crop tomato (Solanum lycopersicum). We identified and cloned the
      single tomato ortholog of the two Arabidopsis Snf2 genes, designated SlCHR1.
      Transgenic tomato plants (cv. Micro-Tom) that constitutively overexpress the
      coding sequence of SlCHR1 show reduced growth in all developmental stages of
      tomato. This confirms that SlCHR1 combines the functions of both Arabidopsis
      genes in tomato. Compared to the wild type, the transgenic seedlings of tomato
      have significantly shorter roots, hypocotyls and reduced cotyledon size.
      Transgenic plants have a much more compact growth habit with markedly reduced
      plant height, severely compacted reproductive structures with smaller flowers and
      smaller fruits. The results indicate that either GMO-based or non-GMO-based
      approaches to modulate the expression of chromatin remodelling ATPase genes could
      develop into methods to control plant growth, for example to replace the use of
      chemical growth retardants. This approach is likely to be applicable and
      attractive for any crop for which growth habit reduction has added value. 

PMID- 25974126
TI  - NF-kappaB p65 Subunit Is Modulated by Latent Transforming Growth Factor-beta
      Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells.
AB  - NF-kappaB is a well-characterized transcription factor, widely known as a key
      player in tumor-derived inflammation and cancer development. Herein, we present
      the functional and molecular relevance of the canonical NF-kappaB p65 subunit in
      nasopharyngeal carcinoma (NPC). Loss- and gain-of-function approaches were
      utilized to reveal the functional characteristics of p65 in propagating tumor
      growth, tumor-associated angiogenesis, and epithelial-to-mesenchymal transition
      in NPC cells. Extracellular inflammatory stimuli are critical factors that
      trigger the NF-kappaB p65 signaling; hence, we investigated the components of the
      tumor microenvironment that might potentially influence the p65 signaling
      pathway. This led to the identification of an extracellular matrix (ECM) protein
      that was previously reported as a candidate tumor suppressor in NPC. Our studies
      on the Latent Transforming Growth Factor-beta Binding Protein 2 (LTBP2) protein
      provides substantial evidence that it can modulate the p65 transcriptional
      activity. Re-expression of LTBP2 elicits tumor suppressive effects that parallel
      the inactivation of p65 in NPC cells. LTBP2 was able to reduce phosphorylation of
      p65 at Serine 536, inhibit nuclear localization of active phosphorylated p65, and
      impair the p65 DNA-binding ability. This results in a consequential down
      regulation of p65-related gene expression. Therefore, the data suggest that the
      overall up-regulation of p65 expression and the loss of this candidate ECM tumor
      suppressor are milestone events contributing to NPC development. 

PMID- 25974128
TI  - Significance of Very-High-Frequency Oscillations (Over 1,000Hz) in Epilepsy.
AB  - OBJECTIVE: We previously reported ictal very-high-frequency oscillations (VHFO)
      of 1,000 to 2,500Hz recorded by subdural macroelectrodes using a 10-kHz sampling
      rate. The purpose of this study was to clarify the clinical significance of ictal
      VHFO in neocortical epilepsy. METHODS: This study included 13 patients with
      neocortical epilepsy who underwent subdural electrode implantation and had at
      least 1 seizure recorded at a 10-kHz sampling rate and were followed for more
      than 2 years postoperatively. Extent of resection was determined considering the
      seizure onset zone (SOZ) and irritative zone, structural lesion, and functional
      areas. Areas showing VHFO and those with HFO were not taken into consideration.
      The presence or absence of VHFO (>1,000 Hz), HFO (200-1,000Hz) and SOZ, and
      completeness of resection of these areas were compared with postoperative seizure
      outcome. RESULTS: Seven patients had favorable (Engel class Ia) and 6 had
      unfavorable outcomes (other classes). VHFO was recorded in 6 of 7 patients with a
      favorable outcome. On the contrary, VHFO was recorded in only 1 of 6 patients
      with unfavorable outcome. The presence of VHFO was significantly associated with
      favorable outcome. VHFO was recorded on a limited number of electrodes, and VHFO
      generating areas were resected completely, whereas HFO-generating areas and/or
      SOZ were not always resected completely in both favorable and unfavorable outcome
      groups. INTERPRETATION: The presence of ictal VHFO may be predictive of favorable
      outcome. Ictal VHFO may be a more specific marker than ictal HFO or SOZ for
      identifying the core of epileptogenic zone.

PMID- 25974129
TI  - Verification of a standardized method for inserting intramuscular
      electromyography electrodes into teres minor using ultrasound.
AB  - The close proximity of the infraspinatus to the teres minor and their functional
      similarity in producing external rotation of the glenohumeral joint make accurate
      insertion of electromyographic (EMG) electrodes into the teres minor difficult
      and questionable even when published guidelines are followed. The primary aim of
      this study was to examine the anatomical support for the current guidelines for
      inserting intramuscular EMG electrodes into the teres minor muscle. The secondary
      aim was to provide a technical description for ultrasound-guided electrode
      insertion into the teres minor. Intramuscular electrodes were inserted into four
      cadaveric shoulders using markings based on the current guidelines. EMG
      electrodes were also inserted into the teres minor of four healthy male
      participants using real-time ultrasound (RTUS) guidance. Systematic dissections
      of the cadaver specimens revealed that the electrode had been successfully
      inserted into the teres minor muscle in only one out of the four. In the
      remaining three specimens, the needle lodged in the infraspinatus muscle belly at
      distances ranging from 3 to 17 mm medial to the teres minor. Using RTUS guidance,
      the electrodes were successfully inserted into the teres minor in all
      participants, as confirmed by visual inspection with RTUS. This study confirms
      that the current EMG electrode insertion guidelines for the teres minor are not
      accurate and RTUS ensures the placement of electrodes into the teres minor rather
      than the adjacent infraspinatus muscle.

PMID- 25974130
TI  - Establishment and characterization of a fish-cell line from the brain of Japanese
      flounder Paralichthys olivaceus.
AB  - A new brain-cell line derived from Japanese flounder Paralichthys olivaceus
      (POBC) was established. POBC was subcultured for 67 passages over the course of
      420 days. The cultured cells were primarily epithelioid-like. Chromosome analysis
      revealed the cell line to possess the normal P. olivaceus diploid karyotype of 2n
      = 48t (telocentric chromosomes). The cells exhibited the astrocyte marker glial
      fibrillary acidic protein by immunocytochemistry, and significant fluorescent
      signals were observed when the cells were transfected with green fluorescent
      protein reporter plasmid. The established POBC would be ideal material for the
      study of function of fish ependyma, the central neuroendocrine system and
      endocrine disruptors in the marine environment. 

PMID- 25974131
TI  - Biosimilar insulins: guidance for data interpretation by clinicians and users.
AB  - Biosimilar insulins are approved copies of insulins outside patent protection.
      Advantages may include greater market competition and potential cost reduction,
      but clinicians and users lack a clear perspective on 'biosimilarity' for
      insulins. The manufacturing processes for biosimilar insulins are manufacturer
      specific and, although these are reviewed by regulators there are few public data
      available to allow independent assessment or review of issues such as intrinsic
      quality or batch-to-batch variation. Preclinical measures used to assess
      biosimilarity, such as tissue and cellular studies of metabolic activity, physico
      chemical stability and animal studies of pharmacodynamics, pharmacokinetics and
      immunogenicity may be insufficiently sensitive to differences, and are often not
      formally published. Pharmacokinetic and pharmacodynamic studies (glucose clamps)
      with humans, although core assessments, have problems of precision which are
      relevant for accurate insulin dosing. Studies that assess clinical efficacy and
      safety and device compatibility are limited by current outcome measures, such as
      glycated haemoblobin levels and hypoglycaemia, which are insensitive to
      differences between insulins. To address these issues, we suggest that all
      comparative data are put in the public domain, and that systematic clinical
      studies are performed to address batch-to-batch variability, delivery devices,
      interchangeability in practice and long-term efficacy and safety. Despite these
      challenges biosimilar insulins are a welcome addition to diabetes therapy and,
      with a transparent approach, should provide useful benefit to insulin users. 

PMID- 25974132
TI  - A draft map of rhesus monkey tissue proteome for biomedical research.
AB  - Though the rhesus monkey is one of the most valuable non-human primate animal
      models for various human diseases because of its manageable size and genetic and
      proteomic similarities with humans, proteomic research using rhesus monkeys still
      remains challenging due to the lack of a complete protein sequence database and
      effective strategy. To investigate the most effective and high-throughput
      proteomic strategy, comparative data analysis was performed employing various
      protein databases and search engines. The UniProt databases of monkey, human,
      bovine, rat and mouse were used for the comparative analysis and also a universal
      database with all protein sequences from all available species was tested. At the
      same time, de novo sequencing was compared to the SEQUEST search algorithm to
      identify an optimal work flow for monkey proteomics. Employing the most effective
      strategy, proteomic profiling of monkey organs identified 3,481 proteins at 0.5%
      FDR from 9 male and 10 female tissues in an automated, high-throughput manner.
      Data are available via ProteomeXchange with identifier PXD001972. Based on the
      success of this alternative interpretation of MS data, the list of proteins
      identified from 12 organs of male and female subjects will benefit future rhesus
      monkey proteome research. 

PMID- 25974134
TI  - Investing in Onchocerciasis Control: Financial Management of the African
      Programme for Onchocerciasis Control (APOC).

PMID- 25974133
TI  - Inhibition and Reversal of Microbial Attachment by an Antibody with Parasteric
      Activity against the FimH Adhesin of Uropathogenic E. coli.
AB  - Attachment proteins from the surface of eukaryotic cells, bacteria and viruses
      are critical receptors in cell adhesion or signaling and are primary targets for
      the development of vaccines and therapeutic antibodies. It is proposed that the
      ligand-binding pocket in receptor proteins can shift between inactive and active
      conformations with weak and strong ligand-binding capability, respectively. Here,
      using monoclonal antibodies against a vaccine target protein - fimbrial adhesin
      FimH of uropathogenic Escherichia coli, we demonstrate that unusually strong
      receptor inhibition can be achieved by antibody that binds within the binding
      pocket and displaces the ligand in a non-competitive way. The non-competitive
      antibody binds to a loop that interacts with the ligand in the active
      conformation of the pocket but is shifted away from ligand in the inactive
      conformation. We refer to this as a parasteric inhibition, where the inhibitor
      binds adjacent to the ligand in the binding pocket. We showed that the receptor
      blocking mechanism of parasteric antibody differs from that of orthosteric
      inhibition, where the inhibitor replaces the ligand or allosteric inhibition
      where the inhibitor binds at a site distant from the ligand, and is very potent
      in blocking bacterial adhesion, dissolving surface-adherent biofilms and
      protecting mice from urinary bladder infection. 

PMID- 25974135
TI  - Stromal CYR61 Confers Resistance to Mitoxantrone via Spleen Tyrosine Kinase
      Activation in Human Acute Myeloid Leukaemia.
AB  - Approximately 50% of children with acute myeloid leukaemia (AML) relapse, despite
      aggressive chemotherapy. The bone marrow stromal environment protects leukaemia
      cells from chemotherapy (i.e., stroma-induced chemoresistance), eventually
      leading to recurrence. Our goal is to delineate the mechanisms underlying stroma
      mediated chemoresistance in AML. We used two human bone marrow stromal cell
      lines, HS-5 and HS-27A, which are equally effective in protecting AML cells from
      chemotherapy-induced apoptosis in AML-stromal co-cultures. We found that CYR61
      was highly expressed by stromal cells, and was upregulated in AML cells by both
      stromal cell lines. CYR61 is a secreted matricellular protein and is associated
      with cell-intrinsic chemoresistance in other malignancies. Here, we show that
      blocking stromal CYR61 activity, by neutralization or RNAi, increased
      mitoxantrone-induced apoptosis in AML cells in AML-stromal co-cultures, providing
      functional evidence for its role in stroma-mediated chemoresistance. Further, we
      found that spleen tyrosine kinase (SYK) mediates CYR61 signalling. Exposure to
      stroma increased SYK expression and activation in AML cells, and this increase
      required CYR61. SYK inhibition reduced stroma-dependent mitoxantrone resistance
      in the presence of CYR61, but not in its absence. Therefore, SYK is downstream of
      CYR61 and contributes to CYR61-mediated mitoxantrone resistance. The CYR61-SYK
      pathway represents a potential target for reducing stroma-induced
      chemoresistance. 

PMID- 25974136
TI  - Nitrogen Oxide Atom-Transfer Redox Chemistry; Mechanism of NO(g) to Nitrite
      Conversion Utilizing MU-oxo Heme-Fe(III)-O-Cu(II)(L) Constructs.
AB  - While nitric oxide (NO, nitrogen monoxide) is a critically important signaling
      agent, its cellular concentrations must be tightly controlled, generally through
      its oxidative conversion to nitrite (NO2(-)) where it is held in reserve to be
      reconverted as needed. In part, this reaction is mediated by the binuclear heme
      a3/CuB active site of cytochrome c oxidase. In this report, the oxidation of
      NO(g) to nitrite is shown to occur efficiently in new synthetic MU-oxo heme
      Fe(III)-O-Cu(II)(L) constructs (L being a tridentate or tetradentate
      pyridyl/alkylamino ligand), and spectroscopic and kinetic investigations provide
      detailed mechanistic insights. Two new X-ray structures of MU-oxo complexes have
      been determined and compared to literature analogs. All MU-oxo complexes react
      with 2 mol equiv NO(g) to give 1:1 mixtures of discrete [(L)Cu(II)(NO2(-))](+)
      plus ferrous heme-nitrosyl compounds; when the first NO(g) equiv reduces the heme
      center and itself is oxidized to nitrite, the second equiv of NO(g) traps the
      ferrous heme thus formed. For one MU-oxo heme-Fe(III)-O-Cu(II)(L) compound, the
      reaction with NO(g) reveals an intermediate species ("intermediate"), formally a
      bis-NO adduct, [(NO)(porphyrinate)Fe(II)-(NO2(-))-Cu(II)(L)](+) (lambdamax = 433
      nm), confirmed by cryo-spray ionization mass spectrometry and EPR spectroscopy,
      along with the observation that cooling a 1:1 mixture of [(L)Cu(II)(NO2(-))](+)
      and heme-Fe(II)(NO) to -125  degrees C leads to association and generation of the
      key 433 nm UV-vis feature. Kinetic-thermodynamic parameters obtained from low
      temperature stopped-flow measurements are in excellent agreement with DFT
      calculations carried out which describe the sequential addition of NO(g) to the
      MU-oxo complex. 

PMID- 25974137
TI  - Neighborhood effects in depressive symptoms, social support, and mistrust:
      Longitudinal analysis with repeated measurements.
AB  - While many associations between neighborhood characteristics and individual well
      being have been reported, there is a lack of longitudinal studies that could
      provide evidence for or against causal interpretations of neighborhood effects.
      This study examined whether neighborhood urbanicity and socioeconomic status were
      associated with within-individual variation in depression, mistrust and social
      support when individuals were living in different neighborhoods with different
      levels of urbanicity and socioeconomic status. Participants were from the Young
      Finns prospective cohort study (N = 3074) with five repeated measurement times in
      1992, 1997, 2001, 2007, and 2011. Neighborhood urbanicity and socioeconomic
      status were measured at the level of municipalities and zip-code areas. Within
      individual variation over time was examined with multilevel regression, which
      adjusted the models for all stable individual differences that might confound
      associations between neighborhood characteristics and individual well-being.
      Social support from friends was higher in urban areas and in areas with higher
      socioeconomic status, whereas social support from the family was higher in rural
      areas. These associations were observed also in the within-individual analyses,
      and they were partly accounted for by employment and socioeconomic status of the
      participants. There were no associations between neighborhood characteristics and
      depression or mistrust. These findings suggest that people receive less support
      from their families and more support from their friends when living in urban
      compared to rural regions of Finland. These differences are partly explained by
      people's changing socioeconomic and employment statuses. 

PMID- 25974138
TI  - Climate change influences on environment as a determinant of Indigenous health:
      Relationships to place, sea ice, and health in an Inuit community.
AB  - This paper contributes to the literature on Indigenous health, human dimensions
      of climate change, and place-based dimensions of health by examining the role of
      environment for Inuit health in the context of a changing climate. We
      investigated the relationship between one key element of the environment - sea
      ice - and diverse aspects of health in an Inuit community in northern Canada,
      drawing on population health and health geography approaches. We used a case
      study design and participatory and collaborative approach with the community of
      Nain in northern Labrador, Canada. Focus groups (n = 2), interviews (n = 22), and
      participant observation were conducted in 2010-11. We found that an appreciation
      of place was critical for understanding the full range of health influences of
      sea ice use for Inuit. Negative physical health impacts were reported on less
      frequently than positive health benefits of sea ice use, which were predominantly
      related to mental/emotional, spiritual, social, and cultural health. We found
      that sea ice means freedom for sea ice users, which we suggest influences
      individual and collective health through relationships between sea ice use,
      culture, knowledge, and autonomy. While sea ice users reported increases in
      negative physical health impacts such as injuries and stress related to changing
      environmental conditions, we suggest that less tangible climate change impacts
      related to losses of health benefits and disruptions to place meanings and place
      attachment may be even more significant. Our findings indicate that climate
      change is resulting in and compounding existing environmental dispossession for
      Inuit. They also demonstrate the necessity of considering place meanings,
      culture, and socio-historical context to assess the complexity of climate change
      impacts on Indigenous environmental health. 

PMID- 25974139
TI  - Intimate association of visceral obesity with non-alcoholic fatty liver disease
      in healthy Asians: A case-control study.
AB  - BACKGROUND AND AIM: To identify factors associated with non-alcoholic fatty liver
      disease (NAFLD) in healthy Asian subjects. METHODS: A propensity score-matched
      case-control study was designed. To investigate the effects of demographic and
      clinical factors on the presence of NAFLD, a baseline-category logit model was
      used. Potential living liver donors with no hepatic steatosis (< 5%: n = 1353,
      group 1) were considered the baseline category, and subjects with mild (5-33%: n
      = 724, group 2) and moderate/severe (> 33%: n = 116, group 3) hepatic steatosis
      were defined as cases. Age and gender were matched between cases and controls,
      which resulted in 83 matched subjects in each of the three groups. The area of
      abdominal (visceral and subcutaneous) fat was directly measured in all subjects
      by unenhanced computed tomography. RESULTS: Serum aspartate aminotransferase,
      alanine aminotransferase (ALT), gamma-glutamyltranspeptidase, total cholesterol
      and triglyceride levels, and visceral fat amount were directly correlated with
      the grade of hepatic steatosis, and high-density lipoprotein cholesterol levels
      were inversely correlated with it (all P values < 0.05). In a multivariate model,
      visceral fat amount was significantly correlated with both mild (group 2) and
      moderate to severe (group 3) NAFLD, with respective odds ratios (ORs) of 1.03
      relative to group 1 (Ps < 0.05). Body mass index (BMI), ALT, and subcutaneous fat
      were significant predictors of only moderate to severe NAFLD (ORs of 0.54, 1.20,
      and 1.02, respectively, for group 3 vs group 1; Ps < 0.05). CONCLUSIONS: Our
      results indicate that visceral adiposity makes non-obese subjects more
      susceptible to NAFLD, compared with subcutaneous fat and BMI.

PMID- 25974141
TI  - Bacterial populations on the surfaces of organic and conventionally grown almond
      drupes.
AB  - AIMS: To compare the bacterial populations on organically and conventionally
      grown almond drupes before and after hull split. METHODS AND RESULTS: We
      constructed 16S rRNA gene libraries, containing approx. 3000 sequences each, from
      the bacteria from organically and conventionally grown drupes before and after
      hull split. We observed that before hull split both conventionally and
      organically grown drupes were colonized by relatively few types of bacteria that
      were mostly common phyllosphere-associated Proteobacteria. However, the
      organically grown drupes contained significantly more Alphaproteobacteria and the
      conventionally grown drupes contained significantly more Gammaproteobacteria. The
      conventionally grown drupes also contained significantly more sequences
      associated with the phylum Actinobacteria. After hull split, we observed a
      significant increase in bacterial diversity, with many newly appearing sequences
      that were not normally associated with the phyllosphere. CONCLUSIONS: Organic and
      conventional growing methodologies influence the types of bacteria on almond
      drupes and hull split results in a burst of microbial diversification.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Production of organic produce is increasing
      due to consumer preferences, but it was unknown how this methodology affects the
      bacterial populations on almond drupes. This is the first study to compare the
      bacterial populations of organically and conventionally grown almond drupes.

PMID- 25974140
TI  - Utilizing magnetization transfer imaging to investigate tissue remodeling in a
      murine model of autosomal dominant polycystic kidney disease.
AB  - PURPOSE: Noninvasive imaging techniques that quantify renal tissue composition
      are needed to more accurately ascertain prognosis and monitor disease progression
      in polycystic kidney disease (PKD). Given the success of magnetization transfer
      (MT) imaging to characterize various tissue remodeling pathologies, it was tested
      on a murine model of autosomal dominant PKD. METHODS: C57Bl/6 Pkd1 R3277C mice at
      9, 12, and 15 months were imaged with a 16.4T MR imaging system. Images were
      acquired without and with RF saturation in order to calculate MT ratio (MTR)
      maps. Following imaging, the mice were euthanized and kidney sections were
      analyzed for cystic and fibrotic indices, which were compared with statistical
      parameters of the MTR maps. RESULTS: The MTR-derived mean, median, 25th
      percentile, skewness, and kurtosis were all closely related to indices of renal
      pathology, including kidney weight/body weight, cystic index, and percent of
      remaining parenchyma. The correlation between MTR and histology-derived cystic
      and fibrotic changes was R(2) = 0.84 and R(2) = 0.70, respectively. CONCLUSION:
      MT imaging provides a new, noninvasive means of measuring tissue remodeling PKD
      changes and may be better suited for characterizing renal impairment compared
      with conventional MR techniques.

PMID- 25974142
TI  - Adaptation of a culturally relevant nutrition and physical activity program for
      low-income, Mexican-origin parents with young children.
AB  - Latino children experience higher rates of obesity than do non-Latino white
      children. Family-centered nutrition interventions can slow the rate of weight
      gain in this population. Ninos Sanos, Familia Sana (Healthy Children, Healthy
      Family) is a 5-year, community-based, participatory research study that targets
      rural Mexican-origin farmworker families with children aged 2 to 8 years in
      California's Central Valley. Adaptation of a culturally relevant obesity
      prevention program involved qualitative research to tailor key obesity prevention
      messages, pilot testing and implementation of key messages and activities at
      family nights, and continual modification to incorporate culturally innovative
      elements. Of the 238 families enrolled, 53% (125) attended the recommended
      minimum of 5 (of 10 possible) classes during the first year. A university and
      community partnership can guide development of a culturally tailored obesity
      prevention program that is suitable for reaching a high-risk Mexican-origin
      audience through cooperative extension and other public health programs. 

PMID- 25974143
TI  - Predictors of smoke-free policies in affordable multiunit housing, North
      Carolina, 2013.
AB  - INTRODUCTION: Smoke-free policies can effectively protect nonsmokers from
      secondhand smoke (SHS) exposure in multiunit housing. We surveyed all affordable
      multiunit housing properties in North Carolina to determine the statewide
      prevalence of smoke-free policies and to identify predictors of smoke-free
      policies. METHODS: Representatives of affordable housing properties in North
      Carolina completed a mailed or online survey during June through October 2013.
      The primary outcome measure was presence of a smoke-free policy, defined as
      prohibiting smoking in all residential units. We used chi(2) analysis and
      multivariate logistic regression to identify correlates of smoke-free policies.
      RESULTS: Of 1,865 eligible properties, responses were received for 1,063 (57%). A
      total of 16.5% of properties had policies that prohibited smoking in all
      residential units, while 69.6% prohibited smoking in indoor common areas. In
      multivariate analysis, an increase in the number of children per unit was
      associated with a decrease in the odds of having a smoke-free policy at most
      properties. Newer properties across all company sizes were more likely to have
      smoke-free policies. Accessing units from interior hallways predicted smoke-free
      policies among medium-sized companies. CONCLUSION: More smoke-free policies in
      affordable multiunit housing are needed to protect vulnerable populations,
      particularly children, from SHS exposure. Public health professionals should
      continue to educate housing operators about SHS and the benefits of smoke-free
      policies at all properties, including older ones and ones where units are
      accessed from outside rather than from an interior hallway.

PMID- 25974144
TI  - Changes in Georgia restaurant and bar smoking policies from 2006 to 2012.
AB  - INTRODUCTION: The purpose of this study is to examine the change in smoking
      policy status among Georgia restaurants and bars from 2006 to 2012 and to
      identify restaurant and bar characteristics that are associated with allowing
      smoking. METHODS: Data were obtained from similar cross-sectional indoor air
      surveys conducted in 2006 and 2012 in Georgia. Both surveys were designed to
      gather information about restaurant and bar smoking policies. Weighted chi(2)
      analyses were performed to identify changes in smoking policy status and other
      variables from 2006 to 2012. Weighted logistic regression analysis was used to
      test for significant associations between an establishment's smoking policy and
      other characteristics. RESULTS: The percentage of restaurants and bars in Georgia
      that allowed smoking nearly doubled, from 9.1% in 2006 to 17.6% in 2012. The
      analyses also showed a significant increase in the percentage of establishments
      that allow smoking when minors are present. Having a liquor license was a
      significant predictor of allowing smoking. CONCLUSION: The Smokefree Air Act was
      enacted in 2005 to protect the health and welfare of Georgia citizens, but study
      results suggest that policy makers should reevaluate the law and consider
      strengthening it to make restaurants and bars 100% smokefree without exemptions.

PMID- 25974145
TI  - The most distinctive causes of death by state, 2001-2010.

PMID- 25974147
TI  - Chronic thromboembolic pulmonary arterial hypertension: a review of the
      literature and novel therapeutic approaches.
AB  - Chronic thromboembolic pulmonary hypertension is defined as pulmonary
      hypertension (PH) caused by single or recurrent pulmonary emboli and is
      characterized by chronic obstruction of the pulmonary arteries leading to
      increased vascular resistance and PH. Also, progressive remodeling may occur in
      occluded and nonoccluded territories. Better understanding of the underlying
      mechanisms and risk factors could improve diagnosis and allow appropriate
      interventions. Pulmonary endarterectomy is an established approach and is
      considered the definitive treatment for chronic PH, resulting from thromboembolic
      disease. Furthermore, percutaneous transluminal pulmonary angioplasty is
      technically feasible, especially for those with peripheral-type of the disease.
      In addition, several agents, including prostanoids, endothelin receptor
      antagonists and phosphodiesterase type-5 inhibitors, have been tested in selected
      patients yielding promising results. Several novel agents are under
      investigation, and extensive research is currently in progress aiming to resolve
      uncertainties in the understanding and treatment of the disease. 

PMID- 25974146
TI  - Initial Findings from a Novel School-Based Program, EMPATHY, Which May Help
      Reduce Depression and Suicidality in Youth.
AB  - We describe initial pilot findings from a novel school-based approach to reduce
      youth depression and suicidality, the Empowering a Multimodal Pathway Towards
      Healthy Youth (EMPATHY) program. Here we present the findings from the pilot
      cohort of 3,244 youth aged 11-18 (Grades 6-12). They were screened for
      depression, suicidality, anxiety, use of drugs, alcohol, or tobacco (DAT),
      quality-of-life, and self-esteem. Additionally, all students in Grades 7 and 8
      (mean ages 12.3 and 13.3 respectively) also received an 8-session cognitive
      behavioural therapy (CBT) based program designed to increase resiliency to
      depression. Following screening there were rapid interventions for the 125
      students (3.9%) who were identified as being actively suicidal, as well as for
      another 378 students (11.7%) who were felt to be at higher-risk of self-harm
      based on a combination of scores from all the scales. The intervention consisted
      of an interview with the student and their family followed by offering a guided
      internet-based CBT program. Results from the 2,790 students who completed scales
      at both baseline and 12-week follow-up showed significant decreases in depression
      and suicidality. Importantly, there was a marked decrease in the number of
      students who were actively suicidal (from n=125 at baseline to n=30 at 12-weeks).
      Of the 503 students offered the CBT program 163 (32%) took part, and this group
      had significantly lower depression scores compared to those who didn't take part.
      There were no improvements in self-esteem, quality-of-life, or the number of
      students using DAT. Only 60 students (2% of total screened) required external
      referral during the 24-weeks following study initiation. These results suggest
      that a multimodal school-based program may provide an effective and pragmatic
      approach to help reduce youth depression and suicidality. Further research is
      required to determine longer-term efficacy, reproducibility, and key program
      elements. TRIAL REGISTRATION: ClinicalTrials.gov NCT02169960.

PMID- 25974148
TI  - Quantitative assessment of the association between AXIN2 rs2240308 polymorphism
      and cancer risk.
AB  - Axin2 is involved in the regulation of Wnt/beta-catenin pathway and implicated in
      cancer development and progression. The association between AXIN2 rs2240308
      polymorphism and cancer risk has been examined in several case-control studies,
      but the conclusions were conflicting. Here we performed a meta-analysis to
      evaluate the role of rs2240308 in cancer risk. A total of 8 studies were included
      in this meta-analysis (1559 cancer cases and 1503 controls). The pooled odds
      ratios (OR) and the 95% confidence intervals (CIs) were assessed to evaluate the
      association of the AXIN2 rs2240308 polymorphism with a susceptibility to cancer.
      A significantly decreased overall cancer risk was observed in the homozygous (TT
      vs. CC), heterozygous (CT vs. CC), dominant (CT+TT vs. CC) and allelic (T vs. C)
      models (P < 0.005), rather than that in the recessive (TT vs. CT+CC) model (P =
      0.092). AXIN2 polymorphism rs2240308 was also associated with decreased cancer
      risk under all five models in lung cancer. However, AXIN2 rs2240308 polymorphism
      was not associated with cancer risk under any above model in Turkish population
      and under homozygous, heterozygous, recessive models in Japanese population.
      These findings indicate that AXIN2 rs2240308 polymorphism significantly and race
      specifically correlates with decreased cancer risk. 

PMID- 25974149
TI  - Single molecules meet genomics: pinpointing precision medicine.

PMID- 25974150
TI  - Inherently stealthy and highly tumor-selective gold nanoraspberries for
      photothermal cancer therapy.
AB  - Owing to their unique optical properties such as large absorption and scattering
      cross section and large enhancement of electromagnetic field at the surface,
      plasmonic nanostructures have received extensive attention as a highly promising
      class of materials for nano-oncology. Most of the existing plasmonic
      nanostructures require extensive post-synthesis treatments and
      biofunctionalization routines to mitigate their cytotoxicity and/or make them
      tumor-specific. Here, we report one-pot synthesis of a novel class of plasmonic
      nanostructures, namely, gold nanoraspberries (GRBs) with tunable size and
      localized surface plasmon resonance by using a naturally abundant polysaccharide,
      chitosan, which acts as a template and capping agent. Significantly, the GRBs,
      which do not require any further biofunctionalization, exhibit excellent
      selectivity to tumor cells, thus enabling locoregional therapy at the cellular
      level. We demonstrate the tumor-selectivity of GRBs by photothermal ablation of
      tumor cells selectively from their co-culture with normal cells. The simple,
      scalable and tumor-selective nature of GRBs makes them excellent candidates for
      translational plasmonics-based nanomedicine. 

PMID- 25974151
TI  - Daily Dysfunction of Autonomic Regulation Based on Ambulatory Blood Pressure
      Monitoring in Patients with Neurally Mediated Reflex Syncope.
AB  - BACKGROUND: The onset of neurally mediated reflex syncope (NMRS) is associated
      with dysfunction of the autonomic regulatory system. Yet relatively little is
      known about the daily conditions of the autonomic regulation system in patients
      with NMRS. This study elucidated characteristics of daily autonomic function
      using ambulatory blood pressure monitoring (ABPM) and evaluated the utility of
      ABPM for NMRS diagnosis. METHODS: Patients with syncope underwent the head-up
      tilt test (HUT) (80 degrees , 30 minutes). If no syncope occurred, the HUT was
      repeated with drug loading. ABPM was performed on a different day. RESULTS: The
      enrolled subjects were 152 consecutive patients with syncope and 12 controls.
      Sixty-four patients with other diseases related to autonomic dysfunction were
      excluded. HUT with/without drug loading was positive in 40 patients (Group P) and
      negative in 48 patients (Group N). The average systolic blood pressure (SBP) in
      daytime was lower in Groups P and N than in the control group (Group C) (P <
      0.05). The average diastolic blood pressure in daytime was also lower in Group P
      than in Group C (P < 0.05). The average standard deviation-SBP at nighttime was
      higher in Groups P and N than in Group C (P < 0.05). In heart rate variability
      analysis, Group P had higher high frequency normalized unit in daytime than
      Groups C and N (P < 0.05, P < 0.1). Low frequency/high frequency was lower in
      Group P than in Group N in both daytime and nighttime (P < 0.1, P < 0.05).
      CONCLUSION: This study suggests that patients with NMRS present with daily vagal
      hyperactivity and sympathetic dysfunction. ABPM may support the diagnosis of
      NMRS.

PMID- 25974152
TI  - Upregulation of microRNA-126 in hepatic stellate cells may affect pathogenesis of
      liver fibrosis through the NF-kappaB pathway.
AB  - Hepatic fibrosis, which results from chronic liver disease, currently lacks
      effective treatment. MicroRNAs, a group of small noncoding RNA molecules, have
      been observed to play an essential role in liver diseases, including hepatic
      fibrosis. In this study, we described the regulation of nuclear factor kappa B
      (NF-kappaB) inhibitor alpha (IkappaBalpha) and its possible signaling pathway by
      miR-126 in human hepatic stellate cell (HSC) line LX-2. The 3'-untranslated
      region (3'-UTR) of IkappaBalpha combined with miR-126 was analyzed by using a
      dual-luciferase reporter assay. Furthermore, the effects of miR-126 on
      IkappaBalpha mRNA and protein and NF-kappaB protein expression were assessed by
      real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)
      and western blot analysis in the human HSC LX-2 cell line transfected with miR
      126 mimic or inhibitor. Moreover, to understand the molecular mechanism of miR
      126 in promoting liver fibrosis through NF-kappaB signaling pathway, the NF
      kappaB downstream signaling factors expression such as transforming growth factor
      (TGF)-beta1 and collagen I mRNA were detected by real-time qRT-PCR. We identified
      that IkappaBalpha is a potential target gene of miR-126, by directly targeting
      its 3'-UTR. Endogenous miR-126 and exogenous miR-126 mimic inhibited IkappaBalpha
      expression. Moreover, overexpression of miR-126 reduced total and the cytoplasm
      IkappaBalpha protein expression and increased total and cytoblast NF-kappaB
      protein expression of LX-2. Conversely, knockdown of miR-126 could inhibit NF
      kappaB activation by upregulation of IkappaBalpha protein expression. Further,
      miR-126 promoted TNF-a-induced TGF-beta1 and collagen I mRNA expression in LX-2
      cells. miR-126 may play an important role in hepatic fibrosis by downregulating
      the expression of IkappaBalpha partly through the NF-kappaB signaling pathway. 

PMID- 25974153
TI  - Genome Engineering of the 2,3-Butanediol Biosynthetic Pathway for Tight
      Regulation in Cyanobacteria.
AB  - Cyanobacteria have gained popularity among the metabolic engineering community as
      a tractable photosynthetic host for renewable chemical production. However,
      though a number of successfully engineered production systems have been reported,
      long-term genetic stability remains an issue for cyanobacterial systems. The
      genetic engineering toolbox for cyanobacteria is largely lacking inducible
      systems for expression control. The characterization of tight regulation systems
      for use in cyanobacteria may help to alleviate this problem. In this work we
      explore the function of the IPTG inducible promoter P(L)lacO1 in the model
      cyanobacterium Synechococcus elongatus PCC 7942 as well as the effect of gene
      order within an operon on pathway expression. According to our experiments,
      P(L)lacO1 functions well as an inducible promoter in S. elongatus. Additionally,
      we found that gene order within an operon can strongly influence control of
      expression of each gene.

PMID- 25974154
TI  - Ketotifen suppression of NF1 neurofibroma growth over 30 years.
AB  - A patient with NF1 was treated with oral ketotifen for 30 years since infancy.
      Review of the patient's course and treatment details establishes a basis for
      reconsideration of several fundamental precepts about NF1 pathogenesis. The data
      suggest a distinctive benefit to treating an NF1 patient with an inhibitor of
      mast cell degranulation before cutaneous neurofibromas are clinically apparent:
      the neurofibromas appear to be arrested at a very early stage of development. The
      patient's skin was especially remarkable for both the paucity of cutaneous
      neurofibromas and the distinctive monotonous uniformity of those present, which
      were small and flat or barely sessile. While the data do not, of themselves,
      prove that ketotifen treatment commencing in childhood preempts neurofibroma
      maturation, in the context of earlier publications, they certainly warrant
      further investigation.

PMID- 25974155
TI  - Direct Pen Writing of High-Tc, Flexible Magnesium Diboride Superconducting
      Arrays.
AB  - High-Tc , flexible MgB2 -nanowire-based superconducting arrays are fabricated via
      a direct pen writing method on both copper foils and poly(dimethylsiloxane)
      (PDMS) substrates. Such superconducting arrays constitute a new approach for
      fabricating superconducting devices. The realization of a PDMS-based device
      demonstrates the potential for expanding this material into other high-Tc
      superconductor systems, which may lead to novel ways of driving the development
      of "real-life" applications.

PMID- 25974156
TI  - Amniotic membrane is a potential regenerative option for chronic non-healing
      wounds: a report of five cases receiving dehydrated human amnion/chorion membrane
      allograft.
AB  - A case series of five patients with a total of six chronic non-healing wounds
      (>30 day duration) were non-randomly selected to evaluate the performance, safety
      and handling properties of dehydrated human amnion/chorion membrane allograft, an
      amniotic membrane scaffolding product. The patients had lower extremity wounds
      that had previously failed standard of care within a university
      outpatient/inpatient wound healing programme. Five wounds treated with dehydrated
      amnion/chorion membrane allograft showed a mean 43% area reduction from baseline
      (51% median) at 3 weeks into treatment and completely healed with a 64-day median
      time to closure (SD +/-27.6 days). One wound worsened at 3 weeks and was found to
      have a complete central vein obstruction that was treated with long-term mild
      compression but still eventually healed at 6 months. Removing this outlier, the
      four responding wounds had a 72% mean and 69% median change in area from
      baseline, at the 3 week point. All five patients received only one application of
      dehydrated human amnion/chorion membrane allograft, and there were no adverse
      events. The product was easy to use, administer and handle. In summary,
      dehydrated human amnion/chorion membrane allograft appears to be a safe,
      effective and easy to use therapy for chronic non-healing wounds. This study
      describes the details of these clinical cases and provides an overview of the
      current evidence on the use of amniotic tissue in clinical practice. 

PMID- 25974157
TI  - Non-steroidal anti-inflammatory drugs and the risk of head and neck cancer: A
      case-control analysis.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (aspirin)
      have been associated with a reduced risk for certain cancers. We explored the
      association between use of NSAIDs and the risk of head and neck cancer (HNC). We
      conducted a case-control analysis in the UK-based Clinical Practice Research
      Datalink (CPRD) among people below the age of 90 years with incident HNC between
      1995 and 2013. Six controls per case were matched on age, sex, calendar time,
      general practice, and number of years of active history in the CPRD prior to the
      HNC diagnosis. Other potential confounders including comorbidities and
      comedication were also evaluated, and we adjusted our final analyses for BMI,
      smoking and alcohol consumption. Our analyses included 2,745 HNC cases and 16,470
      controls. Aspirin or NSAID use overall did not significantly change the HNC risk.
      However, patients with six or more prescriptions for ibuprofen were at a
      statistically significantly reduced risk for HNC (adjusted OR 0.59, 95% CI 0.37
      0.94). The HNC risk tended to decrease with increasing cumulative exposure to
      ibuprofen, and to be more pronounced for cancer of the larynx. To conclude, in
      this large population-based observational study we found a decreased risk for HNC
      associated with regular use of ibuprofen. 

PMID- 25974158
TI  - Migration of titanium dioxide microparticles and nanoparticles through the body
      and deposition in the gingiva: an experimental study in rats.
AB  - The aim of this experimental work was to evaluate deposition of titanium dioxide
      (TiO2 ) microparticles and nanoparticles, which could originate from titanium
      bioimplants, in the gingiva. Wistar rats were injected intraperitoneally (i.p.)
      with a suspension of TiO2 particles of different sizes (150, 10, or 5 nm). The
      rats were killed 12 months post-injection, and the buccal and lingual gingivae
      were resected and evaluated using light and scanning electron microscopy. Energy
      dispersive X-ray spectroscopy (EDS) was used to confirm the presence of titanium
      in deposits of microparticles and nanoparticles, and the concentration of
      titanium in tissues was measured using inductively coupled plasma-mass
      spectrometry (ICP-MS). Histological examination showed that all experimental
      groups exhibited agglomerates, in the gingiva, of titanium particles of
      micrometer size range, with no associated inflammatory response. Higher
      concentrations of titanium traces were shown, by ICP-MS, in both buccal and
      lingual tissues of all experimental groups compared with their matched controls.
      Titanium concentrations were significantly higher in the buccal gingiva than in
      the lingual gingiva, and after injection with 5-nm particles than with 10-nm
      particles in both localizations. Titanium microparticles and nanoparticles
      deposit in the gingiva, and mostly on the buccal side. Gingival deposition of
      titanium could be considered a tissue indicator of tribocorrosion processes of
      titanium bioimplants.

PMID- 25974160
TI  - Is adjuvant chemotherapy omissible in women with T1-2 stage, node-positive,
      luminal A type breast cancer?
AB  - PURPOSE: The aim of this study was to evaluate whether hormonal breast cancer
      therapy without systemic chemotherapy is feasible in adjuvant settings in luminal
      A breast cancer. METHODS: A database of 879 patients who underwent breast cancer
      surgery enrolled between January 2003 and December 2011 was reviewed. Patients
      with luminal A cancers were selected and grouped into those who received adjuvant
      hormonal therapy with (group C+) or without (group C - ) adjuvant systemic
      therapy. RESULTS: In a multivariable analysis, axillary lymph node (ALN)
      metastasis was the only independent factor that revealed significantly different
      between the two groups in disease-free survival (DFS). The 5-year cumulative DFS
      was 82.3 versus 76.2% (P = 0.700) and overall survival (OS) was 83.9 versus 100%
      (P = 0.483) for C+ versus C -  breast cancer, respectively. CONCLUSION: In our
      study, adjuvant chemotherapy in luminal A, T1-2N+ cancer showed no significant
      difference for DFS. We believe that the role of adjuvant chemotherapy for these
      women with hormonal therapy might have little benefit.

PMID- 25974162
TI  - Azidomethyl-EDOT as a Platform for Tunable Surfaces with Nanostructures and
      Superhydrophobic Properties.
AB  - We report for the first time the use of click chemistry both to modify the
      surface morphology and to obtain superhydrophobic properties. Using click
      chemistry as a postfunctionalization of poly(3,4-ethylenedioxythiophene)
      nanofibers bearing azido groups, we show that the nanostructures already present
      on the surface as well as the surface hydrophobicity are highly affected by the
      used alkyne. These results allow one to envisage widely varied strategies to
      modify nanostructured surfaces while introducing various functions, for example
      to produce biosensors or antibacterial surfaces. 

PMID- 25974161
TI  - Diacylglycerol O-acyltransferase type-1 synthesizes retinyl esters in the retina
      and retinal pigment epithelium.
AB  - Retinyl esters represent an insoluble storage form of vitamin A and are
      substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment
      epithelium (RPE). The major retinyl-ester synthase in RPE cells is
      lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent
      retinyl-ester synthase activity has been observed in RPE homogenates but the
      protein responsible has not been identified. Here we show that diacylglycerol O
      acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including
      RPE and Muller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from
      multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in
      dgat1(-/-) mice has no effect on retinal anatomy or the ultrastructure of
      photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in
      dgat1(-/-) mice were also normal. However, the normal build-up of all-trans
      retinyl esters (all-trans-RE's) in the RPE during the first hour after a deep
      photobleach of visual pigments in the retina was not seen in dgat1(-/-) mice.
      Further, total retinyl-ester synthase activity was reduced in both dgat1(-/-)
      retina and RPE.

PMID- 25974164
TI  - A wandering mind does not stray far from home: the value of metacognition in
      distant search.
AB  - When faced with a problem, how do individuals search for potential solutions? In
      this article, we explore the cognitive processes that lead to local search (i.e.,
      identifying options closest to existing solutions) and distant search (i.e.,
      identifying options of a qualitatively different nature than existing solutions).
      We suggest that mind wandering is likely to lead to local search because it
      operates by spreading activation from initial ideas to closely associated ideas.
      This reduces the likelihood of accessing a qualitatively different solution.
      However, instead of getting lost in thought, individuals can also step back and
      monitor their thoughts from a detached perspective. Such mindful metacognition,
      we suggest, is likely to lead to distant search because it redistributes
      activation away from initial ideas to other, less strongly associated, ideas.
      This hypothesis was confirmed across two studies. Thus, getting lost in thoughts
      is helpful when one is on the right track and needs only a local search whereas
      stepping back from thoughts is helpful when one needs distant search to produce a
      change in perspective. 

PMID- 25974166
TI  - Chronic rhinosinusitis: patient experiences of primary and secondary care - a
      qualitative study.
AB  - OBJECTIVES: To explore the experience of CRS and its management from the
      perspective of patients with CRS. To our knowledge, this is the first qualitative
      study exploring sinus disease. DESIGN: Semi-structured qualitative interviews.
      SETTING: ENT outpatient clinic. PARTICIPANTS: Twenty-one adult patients with CRS:
      11 male, 10 female. Patients suffered from a range of types of CRS (including
      polyps and fungal disease) and differing durations of symptoms (1.5-47 years).
      Participants were purposively selected. Thematic analysis was used. OUTCOME
      MEASURES: Patient experience of CRS and its management. RESULTS: Patients had
      concerns regarding management of their symptoms by both healthcare professionals
      and themselves, including delays to referral and repeated medications. They
      reported reduced quality of life and high financial and psychosocial costs
      associated with living with CRS. CONCLUSIONS: Despite guidelines for CRS
      treatment, outcomes remain variable leading to dissatisfaction with treatment.
      Adherence to existing guidelines may result in fewer repeated consultations in
      primary care and earlier referrals to secondary care.

PMID- 25974163
TI  - Electrical stimulation of low-threshold afferent fibers induces a prolonged
      synaptic depression in lamina II dorsal horn neurons to high-threshold afferent
      inputs in mice.
AB  - Electrical stimulation of low-threshold Abeta-fibers (Abeta-ES) is used
      clinically to treat neuropathic pain conditions that are refractory to
      pharmacotherapy. However, it is unclear how Abeta-ES modulates synaptic responses
      to high-threshold afferent inputs (C-, Adelta-fibers) in superficial dorsal horn.
      Substantia gelatinosa (SG) (lamina II) neurons are important for relaying and
      modulating converging spinal nociceptive inputs. We recorded C-fiber-evoked
      excitatory postsynaptic currents (eEPSCs) in spinal cord slices in response to
      paired-pulse test stimulation (500 MUA, 0.1 millisecond, 400 milliseconds apart).
      We showed that 50-Hz and 1000-Hz, but not 4-Hz, Abeta-ES (10 MUA, 0.1
      millisecond, 5 minutes) induced prolonged inhibition of C-fiber eEPSCs in SG
      neurons in naive mice. Furthermore, 50-Hz Abeta-ES inhibited both monosynaptic
      and polysynaptic forms of C-fiber eEPSC in naive mice and mice that had undergone
      spinal nerve ligation (SNL). The paired-pulse ratio (amplitude second eEPSC/first
      eEPSC) increased only in naive mice after 50-Hz Abeta-ES, suggesting that Abeta
      ES may inhibit SG neurons by different mechanisms under naive and nerve-injured
      conditions. Finally, 50-Hz Abeta-ES inhibited both glutamatergic excitatory and
      GABAergic inhibitory interneurons, which were identified by fluorescence in
      vGlut2-Td and glutamic acid decarboxylase-green fluorescent protein transgenic
      mice after SNL. These findings show that activities in Abeta-fibers lead to
      frequency-dependent depression of synaptic transmission in SG neurons in response
      to peripheral noxious inputs. However, 50-Hz Abeta-ES failed to induce cell-type
      selective inhibition in SG neurons. The physiologic implication of this novel
      form of synaptic depression for pain modulation by Abeta-ES warrants further
      investigation. 

PMID- 25974168
TI  - The dynamic deformation of a layered viscoelastic medium under surface
      excitation.
AB  - In this study the dynamic behavior of a layered viscoelastic medium in response
      to the harmonic and impulsive acoustic radiation force applied to its surface was
      investigated both theoretically and experimentally. An analytical solution for a
      layered viscoelastic compressible medium in frequency and time domains was
      obtained using the Hankel transform. A special incompressible case was considered
      to model soft biological tissues. To verify our theoretical model, experiments
      were performed using tissue-like gel-based phantoms with varying mechanical
      properties. A 3.5 MHz single-element focused ultrasound transducer was used to
      apply the radiation force at the surface of the phantoms. A phase-sensitive
      optical coherence tomography system was used to track the displacements of the
      phantom surface. Theoretically predicted displacements were compared with
      experimental measurements. The role of the depth dependence of the elastic
      properties of a medium in its response to an acoustic pulse at the surface was
      studied. It was shown that the low-frequency vibrations at the surface are more
      sensitive to the deep layers than high-frequency ones. Therefore, the proposed
      model in combination with spectral analysis can be used to evaluate depth
      dependent distribution of the mechanical properties based on the measurements of
      the surface deformation.

PMID- 25974167
TI  - Effect of the PPARG2 Pro12Ala Polymorphism on Associations of Physical Activity
      and Sedentary Time with Markers of Insulin Sensitivity in Those with an Elevated
      Risk of Type 2 Diabetes.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is an
      important regulator of metabolic health and a common polymorphism in the PPAR
      gamma2 gene (PPARG2) may modify associations between lifestyle behaviour and
      health. OBJECTIVE: To investigate whether the PPARG2 Pro12Ala genotype modifies
      the associations of sedentary behaviour and moderate-to-vigorous intensity
      physical activity (MVPA) with common measures of insulin sensitivity. METHODS:
      Participants with a high risk of impaired glucose regulation were recruited,
      United Kingdom, 2010-2011. Sedentary and MVPA time were objectively measured
      using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were
      assessed; insulin sensitivity was calculated using Matsuda-ISI and HOMA-IS. DNA
      was extracted from whole blood. Linear regression examined associations of
      sedentary time and MVPA with insulin sensitivity and examined interactions by
      PPARG2 Pro12Ala genotype. RESULTS: 541 subjects were included (average age = 65
      years, female = 33%); 18% carried the Ala12 allele. Both sedentary time and MVPA
      were strongly associated with HOMA-IS and Matsuda-ISI after adjustment for age,
      sex, ethnicity, medication, smoking status and accelerometer wear time. After
      further adjustment for each other and BMI, only associations with Matsuda-ISI
      were maintained. Every 30 minute difference in sedentary time was inversely
      associated with a 4% (0, 8%; p = 0.043) difference in Matsuda-ISI, whereas every
      30 minutes in MVPA was positively associated with a 13% (0, 26%; p = 0.048)
      difference. The association of MVPA with Matsuda-ISI was modified by genotype (p
      = 0.005) and only maintained in Ala12 allele carriers. Conversely, sedentary time
      was not modified by genotype and remained inversely associated with insulin
      sensitivity in Pro12 allele homozygotes. CONCLUSION: The association of MVPA with
      Matsuda-ISI was modified by PPARG2 Pro12Ala genotype with significant
      associations only observed in the 18% of the population who carried the Ala12
      allele, whereas associations with sedentary time were unaffected.

PMID- 25974169
TI  - Dental Floss Traction Assists in Treating Gastrointestinal Mucosal Tumors by
      Endoscopy.
AB  - BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) is a relatively
      new but widely used medical technique that has been used to remove
      gastrointestinal mucosal tumors. This study aimed to identify the usefulness of
      ESD-assisted dental floss traction for the removal of gastrointestinal tumors.
      PATIENTS AND METHODS: This was a retrospective study performed at a single
      institution. From April 2014 to August 2014, 20 consecutive patients presenting
      with gastrointestinal mucosal tumors at Zhongshan Hospital, Fudan University,
      Shanghai, China, were enrolled. The tumor characteristics, en bloc resection
      rates, treatments, and follow-up care practices were evaluated for all patients.
      RESULTS: Of the lesions presenting in the 20 patients, 10 were located in the
      upper gastrointestinal tract, and the remainder were located in the lower
      gastrointestinal tract. All the resected tumors were removed completely without
      interrupting the tumor capsule. No bleeding or perforation occurred, and no
      recurrences were identified at the time of follow-up. CONCLUSIONS: The dental
      floss traction method benefits the ESD procedure during the treatment of
      gastrointestinal mucosal tumors.

PMID- 25974170
TI  - The effect of multimeric adiponectin isoforms and leptin on the function of
      rheumatoid fibroblast-like synoviocytes.
AB  - OBJECTIVES: To evaluate the effects of physiologically relevant concentrations of
      multimeric adiponectin isoforms and leptin on the function of fibroblast-like
      synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHOD: FLS,
      isolated from the synovial tissue of 21 RA patients, were stimulated for 24 h
      with interleukin (IL)-1beta (1 ng/mL) and adiponectin isoforms [fraction enriched
      with high-molecular-weight (HMW) oligomers and middle-molecular-weight (MMW)
      hexamers or low-molecular-weight (LMW) trimers, 10 MUg/mL each], or leptin (10
      ng/mL), either separately or in a combination of IL-1beta and the respective
      adipokine. Moreover, cells were pre-treated for 24 h with adipokines, then
      stimulated for 8 h with IL-1beta. The concentrations of IL-6, IL-8, matrix
      metalloproteinase (MMP)-3, and dickkopf (DKK)-1, an inhibitor of
      osteoblastogenesis, in culture supernatants, as well as the concentrations of
      leptin, HMW, MMW, and LMW adiponectin in sera and synovial fluid (SF) samples,
      were measured by specific enzyme-linked immunosorbent assays (ELISAs). RESULTS:
      In comparison with sera, SF samples contained similar amounts of leptin, lower
      amounts of total adiponectin but a higher proportion of the LMW isoform.
      Separately added IL-1beta and HMW/MMW adiponectin, but not LMW adiponectin or
      leptin, up-regulated the release of IL-6, IL-8, and MMP-3 from FLS but no synergy
      was observed in co-stimulation experiments. However, pre-treatment of FLS with
      HMW/MMW or LMW significantly raised the IL-1beta-triggered secretion of MMP-3 and
      IL-6 or MMP-3, respectively. CONCLUSIONS: Adiponectin not only triggers pro
      inflammatory and pro-destructive activities of rheumatoid FLS but also pre
      disposes these cells to a stronger response to IL-1beta. Thus, it is likely that
      adiponectin is more important in the initiation phase than in the chronic phase
      of RA.

PMID- 25974171
TI  - Why repetition? Repetitive babbling, auditory feedback, and cochlear
      implantation.
AB  - This study investigated the reduplicated, or repetitive vocalizations of hearing
      infants and infants with profound hearing loss with and without cochlear implants
      using a new measure of repetition in order to address questions not only about
      the effects of cochlear implantation on repetitive babbling, but also about the
      reason repetitive vocalizations occur at all and why they emerge around 7 or 8
      months of age in hearing infants. Participants were 16 infants with profound
      hearing loss and 27 hearing infants who participated at a mean age of 9.9 months
      and/or a mean age of 17.7 months. Mean age at cochlear implantation for infants
      with profound hearing loss was 12.9 months, and mean duration of implant use was
      4.2 months. The data show that before cochlear implantation, repetitive
      vocalizations were rare. However, 4 months after cochlear implant activation,
      infants with hearing loss produced both repetitive vocalizations and repetitions
      per vocalization at levels commensurate with their hearing peers. The results
      support the hypothesis that repetition emerges as a means of vocal exploration
      during the time when hearing infants (and infants with cochlear implants) form
      auditory-motor representations and neural connections between cortical areas
      active in syllable production and syllable perception, during the transition from
      nonlinguistic to linguistic vocalization.

PMID- 25974173
TI  - Chemiluminescence detection for microfluidic cloth-based analytical devices
      (MUCADs).
AB  - In this work, we report the first demonstration of chemiluminescence (CL)
      detection for microfluidic cloth-based analytical devices (MUCADs). Wax screen
      printing is used to make cloth channels or chambers, and enzyme-catalyzed CL
      reactions are imaged using an inexpensive charge coupled device (CCD). We first
      evaluate the relationship between the wicking rate and the length/width of cloth
      channel. For our device, the channel length and width between the loading and
      detection chambers are optimized to be 10mm and 3mm. Thus, the detection
      procedure can be accomplished in about 15s on a cloth-based device (15 * 30
      mm(2)) by using 25-MUL sample spotted on it. Next, several parameters affecting
      cloth-based CL intensity are studied, including exposure time, pH, and
      concentrations of luminol and enzyme. Under optimal conditions, a linear
      relationship is obtained between CL intensity and hydrogen peroxide (H2O2)
      concentrations in the range of 0.5-5mM with a detection limit of 0.46 mM.
      Finally, the utility of cloth-based CL is demonstrated for determination of H2O2
      residues in meat samples. On our device, the chicken meat soaked for 6h with 3%
      H2O2 can be detected. Moreover, the supernatant of grinded meat sample can be
      directly applied, without need for other treatments. We believe that MUCADs with
      CL detection could provide a new platform of rapid and low-cost assays for use in
      areas such as food detection and environmental monitoring.

PMID- 25974172
TI  - CONFOLD: Residue-residue contact-guided ab initio protein folding.
AB  - Predicted protein residue-residue contacts can be used to build three-dimensional
      models and consequently to predict protein folds from scratch. A considerable
      amount of effort is currently being spent to improve contact prediction accuracy,
      whereas few methods are available to construct protein tertiary structures from
      predicted contacts. Here, we present an ab initio protein folding method to build
      three-dimensional models using predicted contacts and secondary structures. Our
      method first translates contacts and secondary structures into distance, dihedral
      angle, and hydrogen bond restraints according to a set of new conversion rules,
      and then provides these restraints as input for a distance geometry algorithm to
      build tertiary structure models. The initially reconstructed models are used to
      regenerate a set of physically realistic contact restraints and detect secondary
      structure patterns, which are then used to reconstruct final structural models.
      This unique two-stage modeling approach of integrating contacts and secondary
      structures improves the quality and accuracy of structural models and in
      particular generates better beta-sheets than other algorithms. We validate our
      method on two standard benchmark datasets using true contacts and secondary
      structures. Our method improves TM-score of reconstructed protein models by 45%
      and 42% over the existing method on the two datasets, respectively. On the
      dataset for benchmarking reconstructions methods with predicted contacts and
      secondary structures, the average TM-score of best models reconstructed by our
      method is 0.59, 5.5% higher than the existing method. The CONFOLD web server is
      available at http://protein.rnet.missouri.edu/confold/.

PMID- 25974174
TI  - Colorimetric monitoring of rolling circle amplification for detection of H5N1
      influenza virus using metal indicator.
AB  - A new colorimetric method for monitoring of rolling circle amplification was
      developed. At first H5N1 target hybrids with padlock probe (PLP) and then PLP is
      circularized upon the action of T4 ligase enzyme. Subsequently, the circular
      probe is served as a template for hyperbranched rolling circle amplification
      (HRCA) by utilizing Bst DNA polymerase enzyme. By improving the reaction,
      pyrophosphate is produced via DNA polymerization and chelates the Mg(2+) in the
      buffer solution. This causes change in solution color in the presence of hydroxy
      naphthol blue (HNB) as a metal indicator. By using pH shock instead of heat shock
      and isothermal RCA reaction not only the procedure becomes easier, but also
      application of HNB for colorimetric detection of RCA reaction further simplifies
      the assay. The responses of the biosensor toward H5N1 were linear in the
      concentration range from 0.16 to 1.20 pM with a detection limit of 28 fM.

PMID- 25974175
TI  - Rational design of metallic nanocavities for resonantly enhanced four-wave
      mixing.
AB  - Optimizing the shape of nanostructures and nano-antennas for specific optical
      properties has evolved to be a very fruitful activity. With modern fabrication
      tools a large variety of possibilities is available for shaping both
      nanoparticles and nanocavities; in particular nanocavities in thin metal films
      have emerged as attractive candidates for new metamaterials and strong linear and
      nonlinear optical systems. Here we rationally design metallic nanocavities to
      boost their Four-Wave Mixing response by resonating the optical plasmonic
      resonances with the incoming and generated beams. The linear and nonlinear
      optical responses as well as the propagation of the electric fields inside the
      cavities are derived from the solution of Maxwell's equations by using the 3D
      finite-differences time domain method. The observed conversion-efficiency of near
      infrared to visible light equals or surpasses that of BBO of equivalent
      thickness. Implications to further optimization for efficient and broadband
      ultrathin nonlinear optical materials are discussed. 

PMID- 25974176
TI  - Correction: Oxidation by Neutrophils-Derived HOCl Increases Immunogenicity of
      Proteins by Converting Them into Ligands of Several Endocytic Receptors Involved
      in Antigen Uptake by Dendritic Cells and Macrophages.

PMID- 25974177
TI  - Experimental study of fat grafting under negative pressure for wounds with
      exposed bone.
AB  - BACKGROUND: The combination of fat grafting and negative pressure (VAC) therapy
      represents a synergistic interaction of all essential components for wound
      healing. The aim of this experimental study was to determine whether it could
      promote healing of wounds with exposed bone. METHODS: Full-thickness wounds with
      denuded bone in Sprague-Dawley rats were treated with either polyurethane foam
      dressing, fat grafting alone, polyurethane foam dressing with VAC, or
      polyurethane foam dressing with VAC combined with a single, or two
      administrations of fat graft. Wound healing kinetics, tissue growth, cell
      proliferation (Ki-67) and angiogenesis (platelet endothelial cell adhesion
      molecule 1 and alpha-smooth muscle actin) were investigated. Messenger RNA levels
      related to angiogenesis (vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (b-FGF)), profibrosis (platelet-derived growth factor A
      and transforming growth factor beta), adipocyte expression (fatty acid-binding
      protein (FABP) 4 and peroxisome proliferator activated receptor gamma), and
      extracellular matrix remodelling (collagen I) were measured in wound tissues.
      RESULTS: Wounds treated by VAC combined with fat grafting were characterized by
      cell proliferation, neoangiogenesis and maturation of functional blood vessels;
      they showed accelerated granulation tissue growth over the denuded bone compared
      with VAC- or foam dressing-treated wounds. Fat grafting alone over denuded bone
      resulted in complete necrosis. Expression of angiogenesis markers (VEGF and b
      FGF) and adipocyte expression factors (FABP-4) was upregulated in wounds treated
      with VAC combined with fat grafting. CONCLUSION: Fat grafting with VAC therapy
      may represent a simple but effective clinical solution for a number of complex
      tissue defects, and warrants testing in clinical models. SURGICAL RELEVANCE: The
      combination of fat grafting and vacuum therapy represents a synergistic
      interaction of regenerative cells, hospitable wound matrix and stimulating
      micromechanical forces. It could accelerate complex wound healing through cell
      proliferation, neoangiogenesis and maturation of functional blood vessels. The
      efficacy of a multimodal wound healing approach is established in this
      experimental model; it could easily be translated into clinical trials of
      treatment for difficult wounds.

PMID- 25974178
TI  - Long-range bonding/nonbonding interactions: a donor-acceptor resonance studied by
      dynamic NMR.
AB  - Long-range bonding interactions were evaluated using variable-temperature NMR
      spectroscopy and suitable 2'-CH2X-substituted phenylpyridines (X = Me, NMe2, OMe,
      F). It was found that the arylpyridyl rotational barriers were lower when
      electronegative atoms were bound to the alpha carbon of the 2' moiety. This
      effect was ascribed to a stabilizing interaction in the transition state due to
      the lone pair of the heterocyclic nitrogen with the alpha carbon. Computational
      support for this hypothesis came from CCSD(T)/6-31+G(d) calculations. Steric
      effects of the X moiety were ruled out by comparison of the rotational barriers
      of analogous biphenyls. 

PMID- 25974179
TI  - Total synthesis of neodolastane diterpenes trichoaurantianolides C and D.
AB  - The first total synthesis of trichoaurantianolides C and D is described. An
      enantiocontrolled pathway leads to rapid construction of the tricyclic carbon
      skeleton and establishes the trans-dimethyl geometry of the quaternary bridgehead
      carbons via a reductive cyclization. Application of the pi-allyl Stille cross
      coupling leads to a nonracemic allylic alcohol as a prerequisite for the
      introduction of asymmetry in the cycloheptane system. Two strategies have been
      examined for elaboration of the unsaturated tetrahydrofuranyl ring from a common
      tricyclic intermediate. These efforts reveal a number of unanticipated issues of
      reactivity and significant stereochemical requirements for a novel acyloin
      rearrangement as well as the elimination and cyclodehydration of chiral alpha
      hydroxy ketones. Key reactions leading to completion of the synthesis include the
      stereoselective addition of isopropenyllithium TMEDA complex and a facile
      chemoselective oxidation with selenium dioxide. 

PMID- 25974180
TI  - Temperature dependent conformational change of dengue virus.
AB  - Dengue virus is the causative agent of dengue virus fever. It infects about 400
      million people per year and leads to about 21,000 deaths annually. There is
      available neither a fully successful vaccine nor a successful drug therapy. Some
      dengue virus serotypes undergo a temperature dependent conformational change from
      a 'smooth' form at lower temperatures to a 'bumpy' form at temperatures
      approaching 37 degrees C, the human body temperature. The bumpy structure is less
      stable and is probably an intermediate in the formation of a fusogenic virus
      particle. 

PMID- 25974182
TI  - Mechanical model of geometric cell and topological algorithm for cell dynamics
      from single-cell to formation of monolayered tissues with pattern.
AB  - Geometric and mechanical properties of individual cells and interactions among
      neighboring cells are the basis of formation of tissue patterns. Understanding
      the complex interplay of cells is essential for gaining insight into
      embryogenesis, tissue development, and other emerging behavior. Here we describe
      a cell model and an efficient geometric algorithm for studying the dynamic
      process of tissue formation in 2D (e.g. epithelial tissues). Our approach
      improves upon previous methods by incorporating properties of individual cells as
      well as detailed description of the dynamic growth process, with all topological
      changes accounted for. Cell size, shape, and division plane orientation are
      modeled realistically. In addition, cell birth, cell growth, cell shrinkage, cell
      death, cell division, cell collision, and cell rearrangements are now fully
      accounted for. Different models of cell-cell interactions, such as lateral
      inhibition during the process of growth, can be studied in detail. Cellular
      pattern formation for monolayered tissues from arbitrary initial conditions,
      including that of a single cell, can also be studied in detail. Computational
      efficiency is achieved through the employment of a special data structure that
      ensures access to neighboring cells in constant time, without additional space
      requirement. We have successfully generated tissues consisting of more than
      20,000 cells starting from 2 cells within 1 hour. We show that our model can be
      used to study embryogenesis, tissue fusion, and cell apoptosis. We give detailed
      study of the classical developmental process of bristle formation on the
      epidermis of D. melanogaster and the fundamental problem of homeostatic size
      control in epithelial tissues. Simulation results reveal significant roles of
      solubility of secreted factors in both the bristle formation and the homeostatic
      control of tissue size. Our method can be used to study broad problems in
      monolayered tissue formation. Our software is publicly available. 

PMID- 25974183
TI  - Maturation and Mip-1beta Production of Cytomegalovirus-Specific T Cell Responses
      in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium
      tuberculosis Co-Infections.
AB  - It is well accepted that aging and HIV infection are associated with quantitative
      and functional changes of CMV-specific T cell responses. We studied here the
      expression of Mip-1beta and the T cell maturation marker CD27 within CMVpp65
      specific CD4(+) and CD8(+) T cells in relation to age, HIV and active
      Tuberculosis (TB) co-infection in a cohort of Tanzanian volunteers (<= 16 years
      of age, n = 108 and >= 18 years, n = 79). Independent of HIV co-infection,
      IFNgamma(+) CMVpp65-specific CD4(+) T cell frequencies increased with age. In
      adults, HIV co-infection further increased the frequencies of these cells. A high
      capacity for Mip-1beta production together with a CD27(low) phenotype was
      characteristic for these cells in children and adults. Interestingly, in addition
      to HIV co-infection active TB disease was linked to further down regulation of
      CD27 and increased capacity of Mip-1beta production in CMVpp65-specific CD4+ T
      cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells
      observed during HIV infection and active TB could be associated with increased
      CMV reactivation rates.

PMID- 25974184
TI  - Development and validation of a novel platform-independent metastasis signature
      in human breast cancer.
AB  - PURPOSE: The molecular drivers of metastasis in breast cancer are not well
      understood. Therefore, we sought to identify the biological processes underlying
      distant progression and define a prognostic signature for metastatic potential in
      breast cancer. EXPERIMENTAL DESIGN: In vivo screening for metastases was
      performed using Chick Chorioallantoic Membrane assays in 21 preclinical breast
      cancer models. Expressed genes associated with metastatic potential were
      identified using high-throughput analysis. Correlations with biological function
      were determined using the Database for Annotation, Visualization and Integrated
      Discovery. RESULTS: We identified a broad range of metastatic potential that was
      independent of intrinsic breast cancer subtypes. 146 genes were significantly
      associated with metastasis progression and were linked to cancer-related
      biological functions, including cell migration/adhesion, Jak-STAT, TGF-beta, and
      Wnt signaling. These genes were used to develop a platform-independent gene
      expression signature (M-Sig), which was trained and subsequently validated on 5
      independent cohorts totaling nearly 1800 breast cancer patients with all p-values
      < 0.005 and hazard ratios ranging from approximately 2.5 to 3. On multivariate
      analysis accounting for standard clinicopathologic prognostic variables, M-Sig
      remained the strongest prognostic factor for metastatic progression, with p
      values < 0.001 and hazard ratios > 2 in three different cohorts. CONCLUSION: M
      Sig is strongly prognostic for metastatic progression, and may provide clinical
      utility in combination with treatment prediction tools to better guide patient
      care. In addition, the platform-independent nature of the signature makes it an
      excellent research tool as it can be directly applied onto existing, and future,
      datasets.

PMID- 25974185
TI  - Transoral robotic surgery-assisted excision of a congenital cervical salivary
      duct fistula presenting as a branchial cleft fistula.
AB  - BACKGROUND: Congenital cervical salivary duct fistulae are rare entities and can
      mimic branchial cleft fistulae. Ectopic salivary tissue associated with these
      pharyngocervical tracts may have malignant potential. METHODS AND RESULTS: We
      present a case report of a novel surgical approach and review of the literature.
      A 27-year-old man presented with complaint of drainage from the right side of his
      neck since early childhood. A tract was found from the posterior tonsillar pillar
      into the neck and ectopic salivary tissue was found along the tract. A congenital
      hearing loss was also present. Transoral robotic (TORS)-assisted surgery was used
      in the management of this patient and allowed excellent visualization of the
      pharyngeal component of the lesion and a minimally invasive approach. The patient
      did well with no recurrence. CONCLUSION: TORS was helpful for management of a
      congenital salivary fistula and may be helpful for branchial cleft fistulae.
      These lesions may be associated with the branchio-oto-renal (BOR) syndrome.

PMID- 25974186
TI  - Outcomes Associated With Concurrent Iris-Sutured Intraocular Lens Placement and
      Subluxated Crystalline Lens Extraction.
AB  - IMPORTANCE: We have developed a novel surgical technique, to our knowledge, for
      the management of subluxated crystalline lenses involving preplacement of an iris
      sutured posterior chamber intraocular lens (PCIOL) before pars plana vitrectomy
      and lensectomy. OBJECTIVE: To investigate the outcomes of eyes with subluxated
      crystalline lenses, predominantly a result of Marfan syndrome (14 eyes [58%]) or
      trauma (5 eyes [21%]), that underwent pars plana vitrectomy and lensectomy with
      placement of an iris-sutured PCIOL. DESIGN, SETTING, AND PARTICIPANTS: We
      performed a retrospective, noncomparative case series of 24 eyes from 17
      consecutive adult patients with surgically treated subluxated crystalline lenses
      presenting to the Wilmer Eye Institute at Johns Hopkins Hospital from October 6,
      2006, through May 1, 2013. The mean (SD) postoperative follow-up was 24.4 (20.5)
      months for eyes with at least 6 months of follow-up (last date, October 13,
      2014). We performed the analysis from January 21, 2014, through January 3, 2015.
      MAIN OUTCOMES AND MEASURES: Improvement in best-corrected visual acuity using an
      automated Snellen chart and induction of astigmatism for eyes with at least 6
      months of follow-up (n = 18) and IOL stability during follow-up for all eyes (n =
      24). RESULTS: The mean (SD) age at surgery was 49.4 (10.7 [range, 29-67]) years.
      We found an improvement in mean (SD [95% CI]) best-corrected visual acuity from
      0.66 (0.71 [0.30-1.02]) logMAR preoperatively (Snellen equivalent, approximately
      20/90; range, 20/30 to hand motions) to 0.07 (0.11 [95% CI, 0.01-0.12]) logMAR
      postoperatively (Snellen equivalent, approximately 20/23; range, 20/15 to 20/50).
      We found little change in astigmatism postoperatively (mean change, -0.1 [95% CI,
      -0.5 to 0.13] diopters). Postoperative complications included retinal detachment
      (1 eye [4%]), retained cortical fragment (1 [4%]), cystoid macular edema (2
      [8%]), and IOL subluxation (3 [13%]) owing to haptic slippage within 3 months of
      the procedure. The overall probability of successfully achieving placement of a
      centered iris-sutured PCIOL in patients with follow-up of longer than 6 months (n
      = 18) was 100% (95% CI, 81.5%-100%). CONCLUSIONS AND RELEVANCE: Placement of iris
      sutured PCIOLs at the time of subluxated lens extraction with a pars plana
      surgical approach yields favorable results in terms of postoperative visual
      outcomes and surgical complications. This technique offers an effective procedure
      for surgeons to use when treating clinically significant subluxated crystalline
      lenses.

PMID- 25974187
TI  - Adolescent experiences of anti-obesity drugs.
AB  - Only two anti-obesity drugs (AODs) are frequently prescribed in paediatric
      obesity, orlistat and metformin. Meta-analyses show modest benefit in clinical
      trials, yet analyses of prescribing databases show high levels of discontinuation
      in routine clinical practice. Increased understanding of young people's
      experiences taking AOD could result in improved prescribing and outcomes. Semi
      structured interviews were conducted with young people aged 13-18 years and their
      parents from three specialist obesity clinics, analysed using a general thematic
      coding methodology. Theme saturation was achieved after interviews with 15 young
      people and 14 parents (13 parent-child dyads). Three models were developed. Model
      1 explored factors influencing commencement of AOD. Six themes emerged:
      medication as a way out of obesity, enthusiasm and relief at the prospect of
      pharmaceutical treatment, last ditch attempt for some but not all, passive
      acceptance of medication, fear as a motivating factor, and unique treatments
      needed for unique individuals. Model 2 described the inter-relationship between
      dosing and side effects; side effects were a significant experience for many
      young people, and few adhered to prescribed regimens, independently changing
      lifestyle and dosage to tolerate medications. Model 3 described the patient-led
      decision process regarding drug continuation, influenced primarily by side
      effects and efficacy. Use of AODs is challenging for many adolescents. Multiple
      factors were identified that could be targeted to improve concordance and
      maximize efficacy. 

PMID- 25974188
TI  - Involvement of NMDA glutamate receptors in the acquisition and reinstatement of
      the conditioned place preference induced by MDMA.
AB  - Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result
      of chronic consumption. A greater understanding of the neurobiological basis of
      the rewarding effects of MDMA could contribute to developing effective
      pharmacotherapies for MDMA-related problems. The present study evaluated the role
      of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition
      and reinstatement of conditioned place preference (CPP) induced by MDMA.
      Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with
      5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of
      conditioning (experiment 1), or before a reinstatement test (experiment 2). In
      addition, the effects of memantine on acquisition of chocolate-induced CPP and
      the effects of memantine and MDMA on a passive avoidance task were evaluated.
      Memantine did not exert any motivational effects, but blocked the acquisition of
      MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced
      CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP
      induced by priming with MDMA. Memantine did not block the CPP induced by
      chocolate, and it partially reversed the impairing effects of MDMA on memory. Our
      results demonstrate that NMDARs are involved in acquisition of the conditioned
      rewarding effects of MDMA and in priming-induced reinstatement of CPP following
      extinction. Moreover, they suggest the validity of memantine for the treatment of
      MDMA abuse. 

PMID- 25974189
TI  - Antinociceptive activity of astragaloside IV in the animal model of chronic
      constriction injury.
AB  - To investigate the applicability of astragaloside IV (AG) for the treatment of
      refractory neuropathic pain, we systemically evaluated the antinociceptive
      activity of AG in the animal model of chronic constriction injury. We studied
      behaviors, electrophysiology, and biochemistry from day 2 to day 23 after the
      surgery. We found that when administered intraperitoneally at the dose of 60
      mg/kg, AG caused significant inhibition of allodynia and hyperalgesia induced by
      mechanic and thermal stimuli as well as downregulation of the expressions of a
      series of proteins involved in mediating neuropathic pain in the dorsal root
      ganglia, such as P2X purinoceptor 3, glial cell-derived neurotrophic factor,
      glial cell-derived neurotrophic factor family receptor alpha1, and transient
      receptor potential cation channel subtypes A1 and V1. Further investigation
      showed that AG restored the nerve conduction velocity and the histological
      structure of the damaged sciatic nerve on day 23 after the surgery. Moreover,
      results from immunoelectron microscope showed that glial cell-derived
      neurotrophic factor family receptor alpha1 induced by AG could form a circular
      band in the myelin debris between the injured axons and Schwann cells,
      contributing toward restoration of the damaged nerve. In conclusion, in our
      animal model, AG effectively inhibited the neuropathic pain induced by chronic
      constriction injury.

PMID- 25974191
TI  - Two-step solid-state synthesis of PEPPSI-type compounds.
AB  - The two-step mechanochemical preparation of carbene-pyridine complexes of
      palladium and platinum is reported. The organometallic products, which represent
      a class of commercially available catalysts, are rapidly formed in excellent
      yield proving solvent-free synthesis to be a viable synthetic alternative even in
      the case of NHC-containing compounds. 

PMID- 25974190
TI  - Factors associated with serum soluble inhibitors of Wnt-beta-catenin signaling
      (sclerostin and dickkopf-1) in patients undergoing peritoneal dialysis.
AB  - AIM: Sclerostin and dickkopf-1 (Dkk-1) are soluble inhibitors of Wnt-beta-catenin
      signaling and are involved in decreased bone formation and bone volume in
      patients with various bone diseases. The clinical characteristics of sclerostin
      and Dkk-1 and their impacts on mineral and bone metabolism remain undetermined in
      patients undergoing peritoneal dialysis (PD). METHODS: This cross-sectional study
      investigated the association between serum sclerostin and Dkk-1 levels and
      mineral disorders in 74 outpatients under PD treatment. Levels of sclerostin and
      Dkk-1 in serum, urine, and peritoneal dialysate were determined using enzyme
      linked immunosorbent assay kits. The associations between serum sclerostin and
      Dkk-1 levels and biochemical parameters were evaluated by linear regression
      analyses. RESULTS: Median serum sclerostin and Dkk-1 levels were 138 pmol/L
      (range, 98.3-195.9 pmol/L) and 38.8 pmol/L (range, 28.5-47.1 pmol/L),
      respectively. Both sclerostin and Dkk-1 were excreted into urine and peritoneal
      dialysate. Multivariable linear regression analyses showed that serum sclerostin
      level was significantly associated with age, sex, parathyroid hormone level, and
      renal Kt/V. In contrast, serum Dkk-1 level was associated with platelet count and
      serum fibroblast growth factor 23 level but not with any of the bone metabolic
      markers. CONCLUSION: Serum sclerostin was associated with serum intact
      parathyroid hormone, while Dkk-1 was associated with serum fibroblast growth
      factor 23 in patients undergoing PD. The utility of determining soluble Wnt-beta
      catenin inhibitors levels in patients undergoing PD requires further
      investigation.

PMID- 25974192
TI  - Bioaccumulation and translocation of polyhalogenated compounds in rice (Oryza
      sativa L.) planted in paddy soil collected from an electronic waste recycling
      site, South China.
AB  - The bioaccumulation and translocation of polyhalogenated compounds (PHCs) in rice
      planted in the paddy soils of an electronic waste (e-waste) recycling site were
      investigated, along with the effect of contaminated soils on rice growth. The
      PHCs included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
      (PBDEs), decabromodiphenyl ethane (DBDPE), 1,2-bis(2,4,6-tribromophenoxy) ethane
      (BTBPE), and dechlorane plus (DPs). The morphological development and all
      measured physiological parameters of rice plants except for peroxidase were
      significantly inhibited by e-waste contaminated soils. Specifically, soil-root
      bioaccumulation factors (RCFs) increased with increasing logarithm of octanol
      water partition coefficient (logKow) for PCBs, but decreased for PBDEs. During
      translocation from root to stem, translocation factors (TFs) and logKow were
      positively correlated. However, the accumulation mechanism in the leaf was
      concentration-dependent. In the high concentration exposure group, translocation
      play more important role in determination PHCs burden in leaf than atmospheric
      uptake, with logTF (from stem to leaf) being positively correlated with logKow.
      In contrast, in the low exposure and control groups, logTF (from stem to leaf)
      was negatively correlated with logKow. In addition, Syn-DP was selectively
      accumulated in plant tissues. In conclusion, this study demonstrates that e-waste
      contaminated soils affect rice growth, revealed the rule of the bioaccumulation
      and translocation of PHCs in rice plants. 

PMID- 25974193
TI  - Asymptomatic versus symptomatic atrial fibrillation: A systematic review of
      age/gender differences and cardiovascular outcomes.
AB  - Up to 40% of atrial fibrillation (AF) patients are asymptomatic. Despite this,
      scarce data are available about asymptomatic AF, with regard to its clinical
      profile and relationship to cerebrovascular and cardiovascular risks. Our
      objective was to conduct a systematic review and meta-analysis was to study the
      relationship between age and gender with asymptomatic AF and to establish whether
      patients with asymptomatic AF have a higher risk of death (all-cause and
      cardiovascular) and stroke/systemic thromboembolism, when compared to symptomatic
      AF patients. After a comprehensive search, 6 studies (2 randomized clinical
      trials and 4 observational studies) were entered in the meta-analysis. Despite
      significant heterogeneity, our data show that the prevalence of females amongst
      asymptomatic AF group was significantly less compared to the symptomatic AF group
      (RR, 0.57; 95% CI: 0.52-0.64). No difference in age between asymptomatic and
      symptomatic AF patients (P=0.72) was seen. No differences were found in all-cause
      death between patients with asymptomatic and symptomatic AF (RR, 1.38; 95% CI:
      0.82-2.17), nor in cardiovascular death (RR, 0.85; 95% CI: 0.53-1.36) or
      stroke/thromboembolism (RR, 1.72 95% CI: 0.59-5.08). Asymptomatic AF is more
      associated with male sex, irrespective of age. Both general and cardiovascular
      death risks as well as thromboembolic risk do not seem to be affected by the
      asymptomatic clinical status. Symptomatic status should not determine our
      approach to stroke prevention and other cardiovascular prevention therapies,
      amongst patients with AF. 

PMID- 25974194
TI  - Relation of physical function and physical activity to sarcopenia in hemodialysis
      patients: A preliminary study.

PMID- 25974195
TI  - Response to "Effects of Ivabradine on left ventricular function in patients with
      ischemic heart disease".

PMID- 25974196
TI  - Cardioprotection by gene therapy: A review paper on behalf of the Working Group
      on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology.
AB  - Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre
      , post-, and remote conditionings trigger endogenous cardioprotection that
      renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking
      endogenous cardioprotection by modulating genes involved in cardioprotective
      signal transduction provides an opportunity to reproduce endogenous
      cardioprotection with better possibilities of translation into the clinical
      setting. Genes and signaling pathways by which conditioning maneuvers exert their
      effects on the heart are partially understood. This is due to the targeted
      approach that allowed identifying one or a few genes associated with IRI and
      cardioprotection. Genes critical for signaling pathways in cardioprotection
      include protectomiRs (e.g., microRNA 125b*), ZAC1 transcription factor, pro
      inflammatory genes such as cycloxygenase (COX)-2 and inducible nitric oxide
      synthase (iNOS), antioxidant enzymes such as hemoxygenase (HO)-1, extracellular
      and manganese superoxidase dismutases (ec-SOD and Mg-SOD), heat shock proteins
      (HSPs), growth factors such as insulin like growth factor (IGF)-1 and hepatocyte
      growth factor (HGF), antiapoptotic proteins such as Bcl-2 and Bcl-xL, pro
      apoptotic proteins such as FasL, Bcl-2, Bax, caspase-3 and p53, and proangiogenic
      genes such as TGFbeta, sphingosine kinase 1 (SPK1), and PI3K-Akt. By identifying
      the gene expression profiles of IRI and ischemic conditioning, one may reveal
      potential gene targets responsible for cardioprotection. In this manuscript, we
      review the current state of the art of gene therapy in cardioprotection and
      propose that gene expression analysis facilitates the identification of
      individual genes associated with cardioprotection. We discuss signaling pathways
      associated with cardioprotection that can be targeted by gene therapy to achieve
      cardioprotection. 

PMID- 25974197
TI  - Diagnosis of myocarditis: Current state and future perspectives.
AB  - Myocarditis, i.e. inflammation of the myocardium, is one of the leading causes of
      sudden cardiac death (SCD) and dilated cardiomyopathy (DCM) in young adults, and
      is an important cause of symptoms such as chest pain, dyspnea and palpitations.
      The pathophysiological process of disease progression leading to DCM involves an
      ongoing inflammation as a result of a viral-induced auto-immune response or a
      persisting viral infection. It is therefore crucial to detect the disease early
      in its course and prevent persisting inflammation that may lead to DCM and end
      stage heart failure. Because of the highly variable clinical presentation,
      ranging from mild symptoms to severe heart failure, and the limited available
      diagnostic tools, the evaluation of patients with suspected myocarditis
      represents an important clinical dilemma in cardiology. New approaches for the
      diagnosis of myocarditis are needed in order to improve recognition, to help
      unravel its pathophysiology, and to develop new therapeutic strategies to treat
      the disease. In this review, we give a comprehensive overview of the current
      diagnostic strategies for patients with suspected myocarditis, and demonstrate
      several new techniques that may help to improve the diagnostic work-up. 

PMID- 25974198
TI  - Glyco-Nanoparticles Made from Self-Assembly of Maltoheptaose-block-Poly(methyl
      methacrylate): Micelle, Reverse Micelle, and Encapsulation.
AB  - The synthesis and the solution-state self-assembly of the "hybrid" diblock
      copolymers, maltoheptaose-block-poly(methyl methacrylate) (MH-b-PMMA), into large
      compound micelles (LCMs) and reverve micelle-type nanoparticles, are reported in
      this paper. The copolymers were self-assembled in water and acetone by direct
      dissolution method, and the morphologies of the nanoparticles were investigated
      by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA),
      transmission electron microscopy (TEM), atomic force microscopy (AFM), proton
      nuclear magnetic resonance ((1)H NMR), and fluorescence spectroscopy as a
      function of the volume fraction of the copolymer hydrophobic block, copolymer
      concentration, stirring speed, and solvent polarity. The DLS measurements and TEM
      images showed that the hydrodynamic radius (Rh) of the LCMs obtained in water
      increases with the copolymer concentration. Apart from that, increasing the
      stirring speed leads to polydispersed aggregations of the LCMs. On the other
      hand, in acetone, the copolymers self-assembled into reverse micelle-type
      nanoparticles having Rh values of about 6 nm and micellar aggregates, as revealed
      the results obtained from DLS, AFM, and (1)H NMR analyses. The variation in
      micellar structure, that is, conformational inversion from LCMs to reverse
      micelle-type structures in response to polarity of the solvent, was investigated
      by apparent water contact angle (WCA) and (1)H NMR analyses. This conformational
      inversion of the nanoparticles was further confirmed by encapsulation and release
      of hydrophobic guest molecule, Nile red, characterized by fluorescence
      spectroscopy.

PMID- 25974203
TI  - Multiparametric Magnetic Resonance Imaging in Prostate Cancer Management: Current
      Status and Future Perspectives.
AB  - This article reviews recent and ongoing developments in multiparametric magnetic
      resonance imaging (mpMRI) of the prostate. Advances in T2-weighted imaging,
      diffusion-weighted imaging, dynamic contrast-enhanced imaging, and spectroscopic
      imaging are described along with advances related to radiofrequency coils and
      imaging at high magnetic field. As mpMRI is increasingly becoming routine in
      various aspects of clinical prostate cancer management, its role in detection,
      localization, staging, assessment of aggressiveness, and active surveillance is
      discussed. Combined with growing clinical adoption of the techniques already at
      hand, continual optimization of acquisition techniques and image interpretation
      schemes will further strengthen the role of mpMRI as an important diagnostic test
      in prostate cancer management. 

PMID- 25974204
TI  - Dynamic variation of bioactive compounds and aflatoxins in contaminated Radix
      Astragali during extraction process.
AB  - BACKGROUND: Although increasing attention has been paid to the health threat
      caused by mycotoxins in commodities such as food or medicines, mycotoxin transfer
      processes from crude material to products have raised little concern so far.
      Radix Astragali is a commonly used edible and medicinal herbal plant that is
      susceptible to contamination with aflatoxins from Aspergillus flavus. There have
      been no studies on mycotoxin transfer into pharmaceutical preparations or
      derivative products. RESULTS: To facilitate the aflatoxin reduction and
      bioactivity retention, the dynamic variations of aflatoxins as well as herbal
      compounds, namely calycosin-7-glucoside, astragaloside and formononetin, in Radix
      Astragali contaminated by A. flavus during water decoction and ethanol refluxing
      treatments were evaluated simultaneously by an ultra-fast liquid chromatography
      triple quadrupole linear ion trap mass spectrometry method. After the extraction
      processes, although the amount of alfatoxins was reduced remarkably, aflatoxin
      residuals in preparation still exceed recommended limits, manifesting the great
      need to establish a limit for aflatoxins in herbal extractions or derivative
      products. Meanwhile, due to the hydrolysis of glucoside, water decoction period
      should be no longer than 4 h. CONCLUSIONS: This investigation would benefit from
      the determination of the dynamic variation of aflatoxins in infected herbs in
      preparation treatments, in order to further develop aflatoxin limits in herbal
      preparations.

PMID- 25974205
TI  - A rigorous and optimized strategy for the evaluation of the Boys function kernel
      in molecular electronic structure theory.
AB  - This work is focused on the efficient evaluation of the Boys function located at
      the heart of Coulomb and exchange type electron integrals. Different evaluation
      strategies for individual orders and arguments of the Boys function are used to
      achieve a minimal number of floating-point operations. Based on previous work of
      other groups, two similar algorithms are derived that are compared based on both
      accuracy and efficiency: The first algorithm combines the work of Gill et al.
      (Int. J. Quantum Chem. 1991, 40, 745) and Kazuhiro Ishida (Int. J. Quantum Chem.
      1996, 59, 209 and following work), amplifying the benefits of the two strategies.
      (c) 2015 Wiley Periodicals, Inc. 

PMID- 25974206
TI  - Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in
      high-fat diet-induced obese mice.
AB  - The prevalence of nonalcoholic fatty liver disease (NAFLD) increases with
      increasing body mass index (BMI). However, approximately 40-50% of obese adults
      do not develop hepatic steatosis. The level of inflammatory biomarkers is higher
      in obese subjects with NAFLD compared to BMI-matched subjects without hepatic
      steatosis. We used a casein injection in high-fat diet (HFD)-fed C57BL/6J mice to
      induce inflammatory stress. Although mice on a HFD exhibited apparent phenotypes
      of obesity and hyperlipidemia regardless of exposure to casein injection, only
      the HFD+Casein mice showed increased hepatic vacuolar degeneration accompanied
      with elevated inflammatory cytokines in the liver and serum, compared to mice on
      a normal chow diet. The expression of genes related to hepatic fatty acid
      synthesis and oxidation were upregulated in the HFD-only mice. The casein
      injection further increased baseline levels of lipogenic genes and decreased the
      levels of oxidative genes in HFD-only mice. Inflammatory stress induced both
      oxidative stress and endoplasmic reticulum stress in HFD-fed mice livers. We
      conclude that chronic inflammation precedes hepatic steatosis by disrupting the
      balance between fatty acid synthesis and oxidation in the livers of HFD-fed obese
      mice. This mechanism may operate in obese individuals with chronic inflammation,
      thus making them more prone to NAFLD. 

PMID- 25974207
TI  - Beyond Predation: The Zoophytophagous Predator Macrolophus pygmaeus Induces
      Tomato Resistance against Spider Mites.
AB  - Many predatory insects that prey on herbivores also feed on the plant, but it is
      unknown whether plants affect the performance of herbivores by responding to this
      phytophagy with defence induction. We investigate whether the prior presence of
      the omnivorous predator Macrolophus pygmaeus (Rambur) on tomato plants affects
      plant resistance against two different herbivore species. Besides plant-mediated
      effects of M. pygmaeus on herbivore performance, we examined whether a plant
      defence trait that is known to be inducible by herbivory, proteinase inhibitors
      (PI), may also be activated in response to the interactions of this predator with
      the tomato plant. We show that exposing tomato plants to the omnivorous predator
      M. pygmaeus reduced performance of a subsequently infesting herbivore, the two
      spotted spider mite Tetranychus urticae Koch, but not of the greenhouse whitefly
      Trialeurodes vaporariorum (Westwood). The spider-mite infested tomato plants
      experience a lower herbivore load, i.e., number of eggs deposited and individuals
      present, when previously exposed to the zoophytophagous predator. This effect is
      not restricted to the exposed leaf and persists on exposed plants for at least
      two weeks after the removal of the predators. The decreased performance of spider
      mites as a result of prior exposure of the plant to M. pygmaeus is accompanied by
      a locally and systemically increased accumulation of transcripts and activity of
      proteinase inhibitors that are known to be involved in plant defence. Our results
      demonstrate that zoophytophagous predators can induce plant defence responses and
      reduce herbivore performance. Hence, the suppression of populations of certain
      herbivores via consumption may be strengthened by the induction of plant defences
      by zoophytophagous predators. 

PMID- 25974208
TI  - Quantitative proteomic analysis reveals that anti-cancer effects of selenium
      binding protein 1 in vivo are associated with metabolic pathways.
AB  - Previous studies have shown the tumor-suppressive role of selenium-binding
      protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we
      found that induction of SBP1 showed significant inhibition of colorectal cancer
      cell growth and metastasis in mice. We further employed isobaric tags for
      relative and absolute quantitation (iTRAQ) to identify proteins that were
      involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132
      differentially expressed proteins, among them, 53 proteins were upregulated and
      79 proteins were downregulated. Importantly, many of the differentially altered
      proteins were associated with lipid/glucose metabolism, which were also linked to
      Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT)
      signaling pathways. These results have revealed a novel mechanism that SBP1
      mediated cancer inhibition is through altering lipid/glucose metabolic signaling
      pathways. 

PMID- 25974209
TI  - Magnesium and disturbances in carbohydrate metabolism.
AB  - Magnesium is actively involved in a number of metabolic reactions as an important
      co-factor, with special emphasis on carbohydrate metabolism. After a brief
      overview of the regulation of intra- and extracellular magnesium, the present
      review first describes the regulatory role of magnesium in important metabolic
      pathways involved in energy metabolism and glycaemic control. Next the clinical
      significance of hypomagnesaemic conditions with regard to the management of
      glucose in prediabetic stages, such as insulin resistance/impaired glucose
      tolerance and in type 2 diabetes mellitus are characterized. Cross-sectional as
      well as longitudinal studies suggest that a reduced dietary magnesium intake
      serves as a risk factor for the incidence of both impaired glucose regulation and
      type 2 diabetes. Mechanisms that might be responsible for diabetes-associated
      hypomagnesaemia are discussed. Furthermore, the role of hypomagnesaemia in the
      development and progression of chronic diabetic complications are addressed.
      Finally, the available literature on the effects of magnesium supplementation on
      glycaemic control parameters during prediabetic conditions (preventive approach)
      as well as type 2 diabetes mellitus (therapeutic approach) are reviewed
      systematically. There is considerable evidence that chronic magnesium
      supplementation may delay the progression from impaired glucose regulation to
      type 2 diabetes; however, the effects of oral magnesium supplementation as an
      adjunct therapy for type 2 diabetes are quite heterogeneous with respect to the
      various measures of glycaemic control. The results of this review suggest a
      requirement for critical consideration of the pros and cons of magnesium
      replacement therapy, based on variables such as magnesium status, stage of
      disease and glycaemic control. 

PMID- 25974211
TI  - Managing the Fight against Onchocerciasis in Africa: APOC Experience.

PMID- 25974210
TI  - Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the
      Lungs during Pneumonic Plague.
AB  - Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated
      with a delayed immune response in the lungs. Because neutrophils are the first
      immune cells recruited to sites of infection, we investigated the mechanisms
      responsible for their delayed homing to the lung. During the first 24 hr after
      pulmonary infection with a fully virulent Y. pestis strain, no significant
      changes were observed in the lungs in the levels of neutrophils infiltrate,
      expression of adhesion molecules, or the expression of the major neutrophil
      chemoattractants keratinocyte cell-derived chemokine (KC), macrophage
      inflammatory protein 2 (MIP-2) and granulocyte colony stimulating factor (G-CSF).
      In contrast, early induction of chemokines, rapid neutrophil infiltration and a
      reduced bacterial burden were observed in the lungs of mice infected with an
      avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a
      YopJ mutant revealed the involvement of YopJ in the inhibition of
      chemoattractants expression. However, the recruitment of neutrophils to the lungs
      of mice infected with the mutant was still delayed and associated with rapid
      bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF
      mRNA levels in the lungs were up-regulated early after infection with the mutant,
      their protein levels remained constant, suggesting that Y. pestis may employ
      additional mechanisms to suppress early chemoattractants induction in the lung.
      It therefore seems that prevention of the early influx of neutrophils to the
      lungs is of major importance for Y. pestis virulence. Indeed, pulmonary
      instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to
      rapid homing of neutrophils to the lung followed by a reduction in bacterial
      counts at 24 hr post-infection and improved survival rates. These observations
      shed new light on the virulence mechanisms of Y. pestis during pneumonic plague,
      and have implications for the development of novel therapies against this
      pathogen. 

PMID- 25974213
TI  - Effectiveness of Active Packaging on Control of Escherichia Coli O157:H7 and
      Total Aerobic Bacteria on Iceberg Lettuce.
AB  - Contaminated leafy green vegetables have been linked to several outbreaks of
      human gastrointestinal infections. Antimicrobial interventions that are adoptable
      by the fresh produce industry for control of pathogen contamination are in great
      demand. This study was undertaken to evaluate the efficacy of sustained active
      packaging on control of Escherichia coli O157:H7 and total aerobic bacteria on
      lettuce. Commercial Iceberg lettuce was inoculated with a 3-strain mixture of E.
      coli O157:H7 at 10(2) or 10(4) CFU/g. The contaminated lettuce and un-inoculated
      controls were placed respectively in 5 different active packaging structures.
      Traditional, nonactive packaging structure was included as controls. Packaged
      lettuce was stored at 4, 10, or 22  degrees C for 3 wk and sampled weekly for the
      population of E. coli O157:H7 and total aerobic bacteria. Results showed that
      packaging structures with ClO2 generator, CO2 generator, or one of the O2
      scavengers effectively controlled the growth of E. coli O157:H7 and total aerobic
      bacteria under all storage conditions. Packaging structure with the ClO2
      generator was most effective and no E. coli O157:H7 was detected in samples
      packaged in this structure except for those that were inoculated with 4 log CFU/g
      of E. coli O157:H7 and stored at 22  degrees C. Packaging structures with an
      oxygen scavenger and the allyl isothiocyanate generator were mostly ineffective
      in control of the growth of the bacteria on Iceberg lettuce. The research
      suggests that some of the packaging structures evaluated in the study can be used
      to control the presence of foodborne pathogens on leafy green vegetables. 

PMID- 25974212
TI  - A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages
      I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402.
AB  - Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP
      (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with
      involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers
      radiation to microscopic sites outside of known disease. This phase II study
      aimed to achieve a functional complete response (CR) rate of >=75% to RCHOP and
      (90) Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4
      6 cycles of RCHOP followed by RIT [14.8 MBq/kg (0.4 mCi/kg)]; patients with
      positron emission tomographypositive sites of disease after RCHOP/RIT received 30
      Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage
      I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed
      CR. Forty-eight patients proceeded to RIT. One partial responder after RIT
      received IFRT and achieved a CR. The best response after RCHOP + RIT in all 53
      patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77
      96%). With a median follow-up of 5.9 years, 7 (13%) patients have progressed and
      4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission
      and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early
      stage DLBCL patients. Eighty-nine percent of patients achieved functional CR
      without the requirement of IFRT. This regimen is worthy of further study for
      early stage DLBCL in a phase III trial. 

PMID- 25974214
TI  - A novel allele, HLA-DRB1*10:07 was identified in a Chinese individual.
AB  - HLA-DRB1*10:07 shows one nucleotide different from HLA-DRB1*10:01:01 at position
      328 in exon 2. 

PMID- 25974215
TI  - Photo-distributed lichenoid eruption secondary to direct anti-viral therapy for
      hepatitis C.
AB  - Novel direct anti-viral agents are emerging as effective treatments for hepatitis
      C virus (HCV) and provide an alternative to the year-long standard therapy with
      interferon and ribavirin. However, cutaneous side effects from these new
      medications, including rash, pruritus and photosensitivity, are among the most
      commonly reported adverse events and have resulted in therapy discontinuation in
      some cases. Here, we report two cases of a photo-distributed lichenoid eruption
      that occurred within 1  month of starting anti-viral therapy with simeprevir and
      sofosbuvir without interferon or ribavirin. This report provides the first
      histologic description of the cutaneous eruption associated with direct anti
      viral therapy for HCV and highlights the importance of recognizing and treating
      the often intolerable dermatologic side effects of these novel medications, the
      incidence of which is likely to increase as direct anti-viral agents may become
      the standard of care for HCV. 

PMID- 25974217
TI  - Projection neurons in Drosophila antennal lobes signal the acceleration of odor
      concentrations.
AB  - Temporal experience of odor gradients is important in spatial orientation of
      animals. The fruit fly Drosophila melanogaster exhibits robust odor-guided
      behaviors in an odor gradient field. In order to investigate how early olfactory
      circuits process temporal variation of olfactory stimuli, we subjected flies to
      precisely defined odor concentration waveforms and examined spike patterns of
      olfactory sensory neurons (OSNs) and projection neurons (PNs). We found a
      significant temporal transformation between OSN and PN spike patterns, manifested
      by the PN output strongly signaling the OSN spike rate and its rate of change. A
      simple two-dimensional model admitting the OSN spike rate and its rate of change
      as inputs closely predicted the PN output. When cascaded with the rate-of-change
      encoding by OSNs, PNs primarily signal the acceleration and the rate of change of
      dynamic odor stimuli to higher brain centers, thereby enabling animals to
      reliably respond to the onsets of odor concentrations. 

PMID- 25974218
TI  - Augmentation Shield Grafts.

PMID- 25974216
TI  - Mitochondrial Ca2+ and membrane potential, an alternative pathway for Interleukin
      6 to regulate CD4 cell effector function.
AB  - IL-6 plays an important role in determining the fate of effector CD4 cells and
      the cytokines that these cells produce. Here we identify a novel molecular
      mechanism by which IL-6 regulates CD4 cell effector function. We show that IL-6
      dependent signal facilitates the formation of mitochondrial respiratory chain
      supercomplexes to sustain high mitochondrial membrane potential late during
      activation of CD4 cells. Mitochondrial hyperpolarization caused by IL-6 is
      uncoupled from the production of ATP by oxidative phosphorylation. However, it is
      a mechanism to raise the levels of mitochondrial Ca(2+) late during activation of
      CD4 cells. Increased levels of mitochondrial Ca(2+) in the presence of IL-6 are
      used to prolong Il4 and Il21 expression in effector CD4 cells. Thus, the effect
      of IL-6 on mitochondrial membrane potential and mitochondrial Ca(2+) is an
      alternative pathway by which IL-6 regulates effector function of CD4 cells and it
      could contribute to the pathogenesis of inflammatory diseases. 

PMID- 25974219
TI  - Stomatal closure of Pelargonium * hortorum in response to soil water deficit is
      associated with decreased leaf water potential only under rapid soil drying.
AB  - Soil water deficits applied at different rates and for different durations can
      decrease both stomatal conductance (gs ) and leaf water potential (Psileaf ).
      Understanding the physiological mechanisms regulating these responses is
      important in sustainable irrigation scheduling. Glasshouse-grown, containerized
      Pelargonium * hortorum BullsEye plants were irrigated either daily at various
      fractions of plant evapotranspiration (100, 75 and 50% ET) for 20 days or
      irrigation was withheld for 4 days. Xylem sap was collected and gs and Psileaf
      were measured on days 15 and 20, and on days 16-19 for the respective treatments.
      Xylem sap pH and NO3 (-) and Ca(2+) concentrations did not differ between
      irrigation treatments. Xylem abscisic acid (ABA) concentrations ([ABA]xyl )
      increased within 24 h of irrigation being withheld whilst gs and Psileaf
      decreased. Supplying irrigation at a fraction of daily ET produced a similar
      relationship between [ABA]xyl and gs , but did not change Psileaf . Treatment
      differences occurred independently of whether Psileaf was measured in whole
      leaves with a pressure chamber, or in the lamina with a thermocouple
      psychrometer. Plants that were irrigated daily showed lower [ABA]xyl than plants
      from which irrigation was withheld, even at comparable soil moisture content.
      This implies that regular re-watering attenuates ABA signaling due to maintenance
      of soil moisture in the upper soil levels. Crucially, detached leaves supplied
      with synthetic ABA showed a similar relationship between [ABA]xyl and gs as
      intact plants, suggesting that stomatal closure of P. hortorum in response to
      soil water deficit is primarily an ABA-induced response, independent of changes
      in Psileaf . 

PMID- 25974220
TI  - Higher-order repeat structure in alpha satellite DNA occurs in New World monkeys
      and is not confined to hominoids.
AB  - Centromeres usually contain large amounts of tandem repeat DNA. Alpha satellite
      DNA (AS) is the most abundant tandem repeat DNA found in the centromeres of
      simian primates. The AS of humans contains sequences organized into higher-order
      repeat (HOR) structures, which are tandem arrays of larger repeat units
      consisting of multiple basic repeat units. HOR-carrying AS also occurs in other
      hominoids, but results reported to date for phylogenetically more remote taxa
      have been negative. Here we show direct evidence for clear HOR structures in AS
      of the owl monkey and common marmoset. These monkeys are New World monkey species
      that are located phylogenetically outside of hominoids. It is currently
      postulated that the presence of HOR structures in AS is unique to hominoids. Our
      results suggest that this view must be modified. A plausible explanation is that
      generation of HOR structures is a general event that occurs occasionally or
      frequently in primate centromeres, and that, in humans, HOR-carrying AS became
      predominant in the central region of the centromere. It is often difficult to
      assemble sequence reads of tandem repeat DNAs into accurate contig sequences; our
      careful sequencing strategy allowed us to overcome this problem. 

PMID- 25974221
TI  - An Integrated Metagenomics/Metaproteomics Investigation of the Microbial
      Communities and Enzymes in Solid-state Fermentation of Pu-erh tea.
AB  - Microbial enzymes during solid-state fermentation (SSF), which play important
      roles in the food, chemical, pharmaceutical and environmental fields, remain
      relatively unknown. In this work, the microbial communities and enzymes in SSF of
      Pu-erh tea, a well-known traditional Chinese tea, were investigated by integrated
      metagenomics/metaproteomics approach. The dominant bacteria and fungi were
      identified as Proteobacteria (48.42%) and Aspergillus (94.98%), through
      pyrosequencing-based analyses of the bacterial 16S and fungal 18S rRNA genes,
      respectively. In total, 335 proteins with at least two unique peptides were
      identified and classified into 28 Biological Processes and 35 Molecular Function
      categories using a metaproteomics analysis. The integration of metagenomics and
      metaproteomics data demonstrated that Aspergillus was dominant fungus and major
      host of identified proteins (50.45%). Enzymes involved in the degradation of the
      plant cell wall were identified and associated with the soft-rotting of tea
      leaves. Peroxiredoxins, catalase and peroxidases were associated with the
      oxidation of catechins. In conclusion, this work greatly advances our
      understanding of the SSF of Pu-erh tea and provides a powerful tool for studying
      SSF mechanisms, especially in relation to the microbial communities present. 

PMID- 25974222
TI  - Evaluation of the Antibiotic Resistance and Virulence of Escherichia coli Strains
      Isolated from Chicken Carcasses in 2007 and 2013 from Parana, Brazil.
AB  - The frequent use of antimicrobials in commercial poultry production has raised
      concerns regarding the potential impact of antimicrobials on human health due to
      selection for resistant bacteria. Several studies have reported similarities
      between extraintestinal pathogenic Escherichia coli (ExPEC) strains isolated from
      birds and humans, indicating that these contaminant bacteria in poultry may be
      linked to human disease. The aim of our study was to analyze the frequency of
      antimicrobial resistance and virulence factors among E. coli strains isolated
      from commercial chicken carcasses in Parana, Brazil, in 2007 and 2013. A total of
      84 E. coli strains were isolated from chicken carcasses in 2007, and 121 E. coli
      strains were isolated in 2013. Polymerase chain reaction was used to detect
      virulence genes (hlyF, iss, ompT, iron, and iutA) and to determine phylogenetic
      classification. Antimicrobial susceptibility testing was performed using 15
      antimicrobials. The strains were also confirmed as extended-spectrum beta
      lactamase (ESBL)-producing E. coli with phenotypic and genotypic tests. The
      results indicated that our strains harbored virulence genes characteristic of
      ExPEC, with the iutA gene being the most prevalent. The phylogenetic groups D and
      B1 were the most prevalent among the strains isolated in 2007 and 2013,
      respectively. There was an increase in the frequency of resistance to a majority
      of antimicrobials tested. An important finding in this study was the large number
      of ESBL-producing E. coli strains isolated from chicken carcasses in 2013,
      primarily for the group 2 cefotaximase (CTX-M) enzyme. ESBL production confers
      broad-spectrum resistance and is a health risk because ESBL genes are
      transferable from food-producing animals to humans via poultry meat. These
      findings suggest that our strains harbored virulence and resistance genes, which
      are often associated with plasmids that can facilitate their transmission between
      bacteria derived from different hosts, suggesting zoonotic risks. 

PMID- 25974223
TI  - The Old Made New: Natural Compounds against Erectile Dysfunction.
AB  - The interest toward sex-related diseases keeps growing through the years. In this
      review, we focus our attention on erectile dysfunction (ED), a condition that
      caught much attention especially after the introduction on the market of
      phosphodiesterase 5 inhibitors such as the well-known sildenafil. Here, we
      briefly describe both the etiology of ED and the available treatments, examining
      then extensively some natural derivatives that, coming from traditional medicine,
      could represent promising starting points for the development of alternative
      remedies. In fact, herbal remedies from several parts of the world have been
      traditionally known for long, and were recently reconsidered and are now being
      studied to demonstrate their eventual potential in the treatment of ED. Among the
      various examples reported in the literature and reviewed here, plants and
      extracts containing polyphenols-especially a class of compounds called
      kraussianones-appear to be particularly effective and promising against ED.

PMID- 25974226
TI  - Family members facilitating community re-integration and return to productivity
      following traumatic brain injury - motivations, roles and challenges.
AB  - PURPOSE: This study explores the experiences of family members in supporting
      community re-integration and return to productive occupations of the traumatic
      brain injury (TBI) survivor in order to: (i) describe family members' supportive
      roles, (ii) determine challenges family members experience in supporting the TBI
      survivor; and (iii) identify supports that family members require to maintain and
      enhance their roles. METHODS: This qualitative descriptive study involved 14
      interviews with immediate family members of TBI survivors. Data was analyzed
      using thematic analysis. RESULTS: Family members expressed strong motivation and
      engaged in six key roles to support TBI survivors: researcher, case manager,
      advocate, coach, activities of daily living (ADL)/instrumental ADLs and emotional
      supporter. Personal and family stressors and challenges navigating the health
      care system were perceived as challenges in meeting demands of their supportive
      roles. Stigma also presented a barrier to successful community and vocational re
      integration. Subsequently, family members desired more education related to the
      functional implications of TBI, to be connected to health care and community
      resources, and sought a greater family-centred care approach. CONCLUSIONS: Family
      members require on-going counseling and community supports to prevent burnout and
      allow for their continued engagement in their supportive roles. Further education
      on how to navigate the health care system, access community programs and rights
      to workplace accommodation is also warranted. IMPLICATIONS FOR REHABILITATION:
      Family members are strongly motivated to support survivors' return to productive
      occupation following a traumatic brain injury, but require counseling and
      community support to enable their on-going engagement and prevent burnout. Family
      members can be further empowered through the implementation of family-centred
      care. Family members requested further education on the long-term functional
      implications of TBI, how to navigate the health care system, how to access
      community programs and workers' rights to workplace accommodations.

PMID- 25974227
TI  - Factors perceived by employees regarding their sick leave due to depression.
AB  - PURPOSE: Depression is a leading factor of work disability throughout the world.
      However, a paucity of studies investigated factors related to the development of
      depression in the workplace prior to sick leave. This qualitative study aims to
      describe the factors related to the onset of depression at work prior to sick
      leave. METHOD: This study followed a descriptive interpretive design. Interviews
      were conducted with 22 individuals (15 women) who experienced depression while
      they were employed within an organization. The verbatim transcripts were coded
      using QDA-Miner software. RESULTS: Participants (n = 22) reported that their
      depression was partially or completely related to their work. From the analysis
      of all 22 participants' interviews transcripts, three major themes emerged: (1)
      work-related psychosocial risk factors (e.g. factors related to supervisors'
      attitudes and behaviors), (2) the individual's experience in employment (e.g.
      reactions to symptoms) and (3) the period preceding the sick leave of individuals
      who experienced depression (e.g. communication with the supervisor). CONCLUSIONS:
      These results support the importance of preventive intervention oriented toward
      decreasing psychosocial risks within organizations, and detecting workers at
      risk. Future studies should focus on factors that might influence individuals in
      their decision to reveal or not their difficulties to their supervisors.
      IMPLICATIONS FOR REHABILITATION: The conditions in which employees were working
      before they started their leave of absence should be identified; notably (1)
      relationships with organizational stakeholders (e.g. immediate supervisor,
      colleagues) and (2) psychosocial risk factors (e.g. work overload, over
      commitment). A good relationship between the immediate supervisor and the
      employee is an important factor to prevent sick leave due to depression. The
      supervisors should be informed quickly after the first appearance of depressive
      symptoms in employees in order to implement feasible and appropriate
      accommodations as soon as possible.

PMID- 25974228
TI  - High prevalence of early onset mental disorders among long-term disability
      claimants.
AB  - PURPOSE: To provide information on prevalence, comorbidity, age-of-onset and
      severity of mental disorders among persons claiming disability after long-term
      sickness absence. METHOD: Cross-sectional analysis of a cohort of Dutch
      disability claimants (n = 346). Composite International Diagnostic Interview
      (CIDI) 3.0 was used to generate DSM-IV classifications of mental disorder, age-of
      onset and severity; registry data were used on demographics and ICD-10
      classifications of somatic disorder. RESULTS: The mean age of respondents was
      49.8 (range 22-64). The most prevalent broad categories of mental disorders were
      mood and anxiety disorder with a 12-month prevalence of 28.6% and 32.9%,
      respectively. Mood and most anxiety disorders had ages of onset in adolescence
      and early adulthood. The phobias start at school age. Of all respondents, 33.7%
      had >=1 12-month mental disorder. Co-occurrence of substance use disorders,
      phobias and depression/anxiety disorders is frequent. Urogenital and
      gastrointestinal diseases, and cancer coincide with 12-month mental disorder in
      66.7%, 53.9% and 51.7% of cases, respectively. More than two out of three
      specific mental disorders are serious in terms of disability and days out of
      working role. CONCLUSIONS: Disability claimants constitute a vulnerable
      population with a high prevalence of serious mental disorder, substantial
      comorbidity and ages-of-onset in early working careers. More research is needed
      to help prevent long-term sickness absence and disability of claimants with
      mental health problems. IMPLICATIONS FOR REHABILITATION: This study shows common
      mental disorders, such as mood and anxiety disorders, to be highly prevalent
      among persons claiming disability benefit after long-term sickness absence, to
      have early onsets and to often co-occur with somatic disorders. Professionals in
      primary and occupational health care should assess need for treatment of workers
      at risk, while at the same time being careful not to medicalize normal life
      problems. Insurance physicians assessing disability benefit claims should
      identify factors that caused claimants to call in sick and start interventions to
      promote return to work.

PMID- 25974229
TI  - Feeding ecology of bonobos living in forest-savannah mosaics: Diet seasonal
      variation and importance of fallback foods.
AB  - Primates along with many other animal taxa are forced to cope with large shifts
      in basic ecological conditions because of rapid anthropogenically induced changes
      of their habitats. One of the coping strategies for primates is to adjust their
      diet to these changes, and several studies have demonstrated the importance of
      fallback resources for this. Bonobos, like chimpanzees, might be particularly
      vulnerable to habitat fragmentation because of their high dependence on fruit
      availability. Little is known, however, about bonobo feeding ecology in
      fragmented habitats and their use of fallback resources. In this study, we
      investigate diet seasonal variation and the exploitation of preferred and
      fallback foods in a bonobo population living in forest-savannah mosaics. Results
      show that bonobos have adapted to this fragmented habitat by feeding on only a
      few fruit species, including an important number of non-tree species (liana, herb
      and savannah shrub), in comparison to populations living in dense forests. These
      non-tree plants have been defined as fallback and non-preferred foods, which are
      most probably consumed to maintain high frugivory. Interestingly, we identified
      that preferred foods are all typical of mature forests while fallback resources
      are mainly found in forest edges or disturbed areas. This finding indicates that
      bonobos prefer to use mature forests when feeding, as they do for nesting, but
      extend their range use to forest areas in close proximity to humans when the
      availability of preferred fruits is low. Finally, we show that bonobo diet relies
      heavily on two abundant fallback fruits: Musanga cecropioides and Marantochloa
      leucantha. Other studies have demonstrated that the selection of abundant
      fallback resources enables primates to subsist at high densities and to maintain
      cohesive groups, as observed at this study site. Our findings suggest that
      bonobos living in forest-savannah mosaics can be considered as staple fallback
      food consumers. Am. J. Primatol. 77:948-962, 2015. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 25974230
TI  - A novel image recuperation approach for diagnosing and ranking retinopathy
      disease level using diabetic fundus image.
AB  - Retinal fundus images are widely used in diagnosing and providing treatment for
      several eye diseases. Prior works using retinal fundus images detected the
      presence of exudation with the aid of publicly available dataset using extensive
      segmentation process. Though it was proved to be computationally efficient, it
      failed to create a diabetic retinopathy feature selection system for
      transparently diagnosing the disease state. Also the diagnosis of diseases did
      not employ machine learning methods to categorize candidate fundus images into
      true positive and true negative ratio. Several candidate fundus images did not
      include more detailed feature selection technique for diabetic retinopathy. To
      apply machine learning methods and classify the candidate fundus images on the
      basis of sliding window a method called, Diabetic Fundus Image Recuperation
      (DFIR) is designed in this paper. The initial phase of DFIR method select the
      feature of optic cup in digital retinal fundus images based on Sliding Window
      Approach. With this, the disease state for diabetic retinopathy is assessed. The
      feature selection in DFIR method uses collection of sliding windows to obtain the
      features based on the histogram value. The histogram based feature selection with
      the aid of Group Sparsity Non-overlapping function provides more detailed
      information of features. Using Support Vector Model in the second phase, the DFIR
      method based on Spiral Basis Function effectively ranks the diabetic retinopathy
      diseases. The ranking of disease level for each candidate set provides a much
      promising result for developing practically automated diabetic retinopathy
      diagnosis system. Experimental work on digital fundus images using the DFIR
      method performs research on the factors such as sensitivity, specificity rate,
      ranking efficiency and feature selection time. 

PMID- 25974231
TI  - Electrophysiological and Electroanatomical Mapping of the Right Atrium in
      Persistent Atrial Fibrillation: Relation to Collagen Turnover.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with abnormal atrial
      substrate. We investigated whether patients with persistent lone AF and patients
      with persistent AF and nonischemic dilated cardiomyopathy (NIDCM) exhibit any
      differences in electrophysiological and electroanatomical properties of right
      atrium (RA) and collagen turnover. We also investigated the relationship between
      mean RA bipolar voltage and collagen turnover. METHODS: Ten patients with a
      history of persistent lone AF and eight patients with a history of persistent AF
      and NIDCM were studied. Sinus node recovery times (SNRTs) and effective
      refractory periods (ERPs) at 600 ms, 500 ms, and 400 ms from the high (HLRA) and
      low (LLRA) lateral RA, proximal coronary sinus (pCS), and right atrial appendage
      (RAA) were evaluated, and RA electroanatomic mapping was created. Serum N
      terminal propeptide of collagen type I (PINP), cross-linked C-terminal
      telopeptide of collagen type I (CTx), matrix metalloproteinase-1 (MMP-1), and
      tissue inhibitor of matrix metalloproteinases (TIMP-1) were measured as markers
      of collagen synthesis and degradation. RESULTS: No differences were found in
      SNRTs, ERPs from the HLRA, LLRA at 600 ms, pCS and RAA, mean RA bipolar voltage,
      serum PINP, CTx, MMP-1, and TIMP-1 between the two groups. In persistent lone AF,
      serum levels of TIMP-1 were related with mean HLRA and HPRA bipolar voltage.
      CONCLUSIONS: Persistent AF patients with or without NIDCM, demonstrate similar
      changes in electrophysiological and electroanatomical properties of the RA, as
      well as similar structural changes. Moreover, serum markers of collagen synthesis
      are correlated with bipolar voltage in specific regions of RA in persistent lone
      AF.

PMID- 25974232
TI  - Consider the neuro-cardiac continuum of Coffin-Lowry syndrome!

PMID- 25974233
TI  - Designed Intercalators for Modification of DNA Origami Surface Properties.
AB  - The modification of the backbone properties of DNA origami nanostructures through
      noncovalent interactions with designed intercalators, based on acridine
      derivatized with side chains containing esterified fatty acids or oligo(ethylene
      glycol) residues is reported. Spectroscopic analyses indicate that these
      intercalators bind to DNA origami structures. Atomic force microscopy studies
      reveal that intercalator binding does not affect the structural intactness but
      leads to altered surface properties of the highly negatively charged
      nanostructures, as demonstrated by their interaction with solid mica or graphite
      supports. Moreover, the noncovalent interaction between the intercalators and the
      origami structures leads to alteration in cellular uptake, as shown by confocal
      microscopy studies using two different eukaryotic cell lines. Hence, the
      intercalator approach offers a potential means for tailoring the surface
      properties of DNA nanostructures. 

PMID- 25974234
TI  - Modified Sliding Technique (MoST) for Penile Lengthening with Insertion of
      Inflatable Penile Prosthesis.

PMID- 25974235
TI  - Mesenchymal stem cell therapy for the treatment of erectile dysfunction.

PMID- 25974236
TI  - Comment on: Is Pornography Use Associated with Sexual Difficulties and
      Dysfunctions among Younger Heterosexual Men?

PMID- 25974237
TI  - Comment on: Exercise Overcomes Possible Influences of Race and Obesity.

PMID- 25974238
TI  - Lifetime Lubricant Use among a Nationally Representative Sample of Lesbian- and
      Bisexual-Identified Women in the United States.
AB  - INTRODUCTION: The diversity in self-identified lesbian and bisexual women's
      sexual interactions necessitates better understanding of how and when they
      integrate personal lubricant into different experiences. However, little is known
      about lesbian and bisexual women's lifetime lubricant use, particularly at the
      population level. AIMS: The aim of this study was to examine the prevalence and
      characteristics of lubricant use among adult lesbian and bisexual women in the
      United States. METHODS: Data were drawn from a subset of lesbian and bisexual
      participants who participated in the 2012 National Survey of Sexual Health and
      Behavior, an online questionnaire administered to a nationally representative
      probability sample of U.S. adults ages 18 and older. MAIN OUTCOME MEASURES: We
      examined socio-demographic characteristics, recent and lifetime lubricant use,
      lubricant use in associated with specific sexual behaviors and condom use,
      frequency of use, motivations for use, as well as perception of lubricant when
      used. RESULTS: A majority of lesbian- (60.1%) and bisexual-identified (77.1%)
      women reported ever using lubricant; 25.7% of lesbian women and 32.7% of bisexual
      women used it in the last 30 days. Across most age groups, lubricant was commonly
      used during partnered sexual play, partnered sexual intercourse, or when a
      vibrator/dildo was used. Lesbian and bisexual women reported using lubricants to
      increase arousal/sexual pleasure/desire, to make sex more fun, or to increase
      physical comfort during sex. CONCLUSIONS: Lubricant use is identified as a part
      of lesbian and bisexual women's sexual experience across the life span, as a part
      of both solo and partnered experiences. As part of evolving sexual health
      assessments, clinicians and health educators may find value in integrating
      lubricant-focused conversation with their lesbian and bisexual patients and
      clients, particularly.

PMID- 25974239
TI  - Editorial Comment to Prostatic arterial embolization for the treatment of lower
      urinary tract symptoms as a result of large benign prostatic hyperplasia: A
      prospective single-center investigation.

PMID- 25974240
TI  - The utility of an artificial substitute to improve corneal sensitivity in
      glaucomatous patients on chronic therapy with prostaglandin analogs.
AB  - PURPOSE: To evaluate whether a tear substitute can improve corneal subepithelial
      nerve plexus and corneal sensitivity in glaucomatous patients. METHODS: This
      study was prospective, longitudinal, and single arm. Twenty glaucomatous patients
      were recruited. All the patients were treated with a prostaglandin analog with
      preservative for at least 1 year. Preservative-free artificial tears (0.5%
      tamarind seed polysaccharide 0.5((r)) eye drops single-dose preservative free
      [Oftagen]) were prescribed thrice per day. The participants were subjected to
      clinical and instrumental evaluation at baseline (T0), after 1 month (T1) and
      after 3 months (T3) of treatment. All patients were examined with a digital
      corneal confocal laser-scanning microscope (HRT II Rostock Cornea Module;
      Heidelberg Engineering GmbH) and Cochet-Bonnet corneal esthesiometer. RESULTS:
      After the artificial substitute, corneal and conjunctival sensitivity
      significantly (P < 0.001) improved at T1 and T3 compared to the baseline. A
      significant correlation was found between break-up time and both central corneal
      sensitivity and the number of fibers. CONCLUSION: The use of a preservative-free
      artificial substitute in association with a topical therapy with chronic
      preservative could increase the compliance of patients.

PMID- 25974241
TI  - Differential beta3 and beta1 Integrin Expression in Bone Marrow and Cortical Bone
      of Estrogen Deficient Rats.
AB  - Integrin-based (beta3 ) attachments to the extracellular matrix (ECM) on
      osteocyte cell processes have recently been proposed to play an important role in
      facilitating osteocyte mechanosensation. However, it is not yet known whether
      integrin expression is altered in the mechanoregulatory osteocytes during
      osteoporosis. The objective of this study was to test the hypothesis that the
      expression of integrin-based mechanosensory complexes (beta1 and beta3 integrins)
      is altered as a direct response to estrogen deficiency, in an estrogen deficient
      animal model of osteoporosis. Four weeks post-operatively, immunohistochemistry
      was used to detect for beta1 and beta3 integrin subunits in bone tissue and
      marrow of ovariectomized (OVX; N = 4) and SHAM (N = 4) operated animals. A
      tartrate resistant acid phosphatase (TRAP) control stain was performed to
      quantify the presence of osteoclasts in the bone marrow and bone surfaces. Image
      analysis was performed to quantify expression patterns in different biological
      compartments, that is, bone marrow, endosteum, and cortical bone. Our results
      showed that beta1 integrins were ubiquitously expressed throughout the bone and
      marrow, for both OVX and SHAM groups. beta3 integrin subunit expression was lower
      in bone cells from osteoporotic animals compared to controls, whereas beta3
      expression in marrow cells did not differ significantly between groups. At the
      endosteum no difference was observed in beta3 integrin subunit expression. As
      expected, the number of osteoclasts was higher in the OVX group validating an
      imbalance in bone remodeling. We propose that a reduction in beta3 integrin
      expression in osteocytes might impair mechanosensation by bone cells during
      estrogen deficiency.

PMID- 25974242
TI  - Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a
      rat model of endometriosis plus ureteral calculosis: role of mast cells.
AB  - The effects of ultramicronized palmitoylethanolamide were evaluated on pain
      behaviours and markers of mast cell (MC) activity in a rat model of endometriosis
      plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH).
      Female Sprague-Dawley rats that underwent surgical induction of endometriosis
      were randomly assigned to receive active (ultramicronized palmitoylethanolamide
      10 mg.kg(-1).d(-1), orally) or placebo treatment for 25 days. At day 21, they
      underwent ureteral stone formation and were video-recorded till day 25 to
      evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral
      condition and number and diameter of endometrial cysts were evaluated. The
      following were then measured: number and percentage of degranulating MCs, number
      of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth
      factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia
      (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats
      showed significantly lower number, duration and complexity of ureteral crises,
      shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004);
      a significantly higher percentage of expelled stones (P < 0.0001); significantly
      lower MC number (P < 0.01), vessel number (P < 0.01), chymase (P < 0.05), NGF (P
      < 0.05), VEGF (P < 0.01), and Flk-1 (P < 0.01) expression in cysts and NGF
      expression in DRG (P < 0.01). In all animals, the global duration of ureteral
      crises correlated linearly and directly with cyst diameter, MC number and chymase
      in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized
      palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by
      modulating MC expression/activity in cysts, thus reducing central sensitization
      due to noxious signals from endometriotic lesions. The results suggest potential
      utility of the compound for VVH in clinics.

PMID- 25974243
TI  - The Pathogenesis of Raised Intraocular Pressure in Uveitis.
AB  - AIM: To analyze current understanding of the factors that contribute to raised
      intraocular pressure (IOP) in patients with uveitis. METHODS: A pubmed literature
      review was carried out using words including "uveitic glaucoma", "IOP AND
      uveitis", "ocular hypertension AND uveitis", "inflammation AND glaucoma",
      "aqueous dynamics" AND "glaucoma/uveitis". RESULTS: Of the two studies looking at
      the aqueous dynamics in experimentally induced uveitis, both found aqueous flow
      decreased acutely, and one found that uveoscleral outflow increased. This is
      likely to reflect the types of uveitis that present acutely with hypotony. A
      study examining patients with Fuch's heterochromic cyclitis found no difference
      in aqueous flow or uveoscleral outflow. No studies have examined aqueous dynamics
      in types of uveitis that present with acutely raised IOP. Levels of
      prostaglandins rise in acute uveitis, which has been shown to increase
      uveoscleral and trabecular outflow, without affecting aqueous flow. Studies have
      demonstrated that raised levels of trabecular protein reduce trabecular outflow.
      Steroid treatment, inflammatory cells, free radicals and enzymes are also likely
      to contribute to the development of raised pressure. When considering the impact
      of the pathogenesis of raised pressure in uveitis on its treatment,
      prostaglandins may provide good intraocular pressure control, but there are
      concerns regarding their theoretical ability to worsen the inflammatory response
      in uveitis. Studies have not conclusively proven this to be the case. Surgical
      success rates vary, but trabeculectomy plus an antimetabolite, deep sclerectomy
      plus an antimetabolite, and Ahmed valve surgery have been used. CONCLUSIONS:
      Uveitic glaucoma is caused by a number of different diseases, some of which
      present with acute hypotony, others with acutely raised IOP, and others which
      demonstrate an increase in IOP over time. Further studies should be carried out
      to examine the differing pathogenesis in these types of diseases, and to
      establish the best treatment options.

PMID- 25974244
TI  - Laparoscopic Radical Nephrectomy of Wilms' Tumor and Renal Cancer in Children:
      Preliminary Experience from a Two-Center Study in China.
AB  - BACKGROUND: To report the preliminary experience of laparoscopic radical
      nephrectomy (LRN) in children with Wilms' tumor (WT) and renal cancer. PATIENTS
      AND METHODS: From January 2010 to October 2013, the medical records of 7 cases of
      WT or renal cancer in children treated by LRN at two medical centers in China
      were reviewed. RESULTS: All the patients were treated by LRN, and 3 of them
      underwent preoperative chemotherapy before surgery. The biggest tumor size was 10
      cm without crossing the lateral edge of the vertebra at the time of operation.
      The median hospital stay was 8.5 days (range, 6-11 days). The pathologic
      investigation showed 5 cases of WT, 1 case of rhabdoid tumor, and 1 case of renal
      cell carcinoma. With a median follow-up of 1.9+/-1.5 years (range, 0.3-2.9
      years), six children were in complete remission, and the remaining one was lost
      to follow-up. None of these patients presented evidence of oncological
      complications (tumoral recurrences, port-site implantation, or secondary lung
      metastases), and no small bowel obstruction occurred. CONCLUSIONS: LRN for WT and
      renal cancer may be considered as an option in selected children. Preoperative
      chemotherapy is to decrease tumor size and to facilitate the dissection, avoiding
      tumor rupture. For trained laparoscopic surgeons, the eventual indication of LRN
      is the tumor not crossing the midline. A long follow-up and more cases are
      necessary to evaluate the results of the laparoscopic approach.

PMID- 25974245
TI  - The outcome of septorhinoplasty surgery on olfactory function.
AB  - OBJECTIVES: To assess olfactory outcomes in patients undergoing septorhinoplasty
      surgery in our unit. DESIGN: Prospective cohort study. SETTING: The Royal
      National Throat Nose and Ear Hospital, London. PARTICIPANTS: Forty-three patients
      undergoing functional septorhinoplasty (Males = 26; mean age = 34.1 +/- 12.2)
      were recruited into the study. MAIN OUTCOME MEASURES: The primary outcome of
      olfactory function was assessed using 'Sniffin sticks'. Our secondary outcomes
      were assessment of patient quality of life using the disease specific Sino-nasal
      Outcome Test-23 questionnaire (SNOT-23) and a visual analogue scale for sense of
      smell. These measures were repeated at 12 weeks post operatively. RESULTS: There
      was a significant change in the Sniffin' sticks score post-operatively (8.3
      versus 9.6; P < 0.001). The SNOT-23 score also showed a significant improvement
      post-operatively (53.5 versus 40.4; P < 0.001). A significant improvement was not
      found in the smell/taste question (question 21) of the SNOT-23 questionnaire as
      well as the visual analogue scale for sense of smell. A difference in olfactory
      outcome was not found between open versus closed approaches, primary versus
      revision surgery and traumatic versus non traumatic cases. CONCLUSIONS: The
      results show a measured significant improvement in olfaction following functional
      Septorhinoplasty but not a subjective improvement in the patients perception of
      their sense of smell and hence not a clinically significant difference. The
      reasons for the measured improvement are not clear and are likely to be
      multifactorial.

PMID- 25974246
TI  - Inversion of the broken ray transform in the case of energy-dependent
      attenuation.
AB  - Broken Ray transform (BRT) arises when one considers a narrow x-ray beam
      propagating through medium under the assumption of single scattering. Previous
      algorithms for inverting the BRT assumed that the medium is characterized by a
      single attenuation coefficient MU. However x-rays lose their energy after Compton
      scattering and the energy loss depends on the scattering angle. Since the
      attenuation coefficient depends on energy, the MU's before and after scattering
      are different. When there are three or more detectors one should distinguish not
      only between MU's that are 'seen' by x-rays before and after scattering, but also
      between MU's that are 'seen' by x-rays traveling towards different detectors.The
      main thrust of this paper is inversion of the BRT with N ? 3 detectors under the
      assumption that the attenuation coefficient can be accurately approximated by a
      linear function of energy within the window of relevant energies. When the number
      of detectors is four or greater, we derive a family of inversion formulas. If N >
      4, we find the optimal formula, which provides the best stability with respect to
      noise in the data. If N = 4, the family collapses into a single formula and no
      optimization is possible. If MU is independent of energy, N = 3 is sufficient for
      inversion. We also develop iterative reconstruction algorithms that can use
      global and local data. The results of testing the algorithms are presented.

PMID- 25974247
TI  - Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers
      in Japanese Patients with Familial Mediterranean Fever.
AB  - OBJECTIVES: The genotype-phenotype correlation of MEFV remains unclear for the
      familial Mediterranean fever (FMF) patients, especially without canonical MEFV
      mutations in exon 10. The risk of FMF appeared to be under the influence of other
      factors in this case. The contribution of HLA polymorphisms to the risk of FMF
      was examined as strong candidates of modifier genes. METHODS: Genotypes of HLA-B
      and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients,
      who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The
      effects of carrier status were evaluated for the risk of FMF by odds ratio (OR).
      The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with
      certain MEFV genotypes and responsiveness to colchicine treatment. RESULTS: The
      carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012),
      whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying
      Bonferroni's correction for multiple statistical tests (n = 28, p<0.00179). The
      protective effect of DRB1*15:02 was completely disappeared in the co-existence of
      B*40:01. The HLA effects were generally augmented in the patients without a
      canonical MEFV variant allele M694I, in accordance with the notion that the lower
      penetrance of the mutations is owing to the larger contribution of modifier genes
      in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine
      resistant patients and 13.5% of 156 colchicine-responders possessed B*35:01
      allele, giving OR of 4.82 (p = 0.0041). CONCLUSIONS: The differential effects of
      HLA class I and class II polymorphisms were identified for Japanese FMF even in
      those with high-penetrance MEFV mutations.

PMID- 25974248
TI  - Structural diversity of the epigenetics pocketome.
AB  - Protein families involved in chromatin-templated events are emerging as novel
      target classes in oncology and other disease areas. The ability to discover
      selective inhibitors against chromatin factors depends on the presence of
      structural features that are unique to the targeted sites. To evaluate challenges
      and opportunities toward the development of selective inhibitors, we calculated
      all pair wise structural distances between 575 structures from the protein
      databank representing 163 unique binding pockets found in protein domains that
      write, read or erase post-translational modifications on histones, DNA, and RNA.
      We find that the structural similarity of binding sites does not always follow
      the sequence similarity of protein domains. Our analysis reveals increased risks
      of activity across target-class for compounds competing with the cofactor of
      protein arginine methyltransferases, lysine acetyltransferases, and sirtuins,
      while exploiting the conformational plasticity of a protein target is a path
      toward selective inhibition. The structural diversity landscape of the
      epigenetics pocketome can be explored via an open-access graphic user interface
      at thesgc.org/epigenetics_pocketome.

PMID- 25974249
TI  - Anatomy and Wikipedia.

PMID- 25974251
TI  - Efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with
      inflammatory bowel disease: A retrospective multicenter study.
AB  - BACKGROUND AND AIM: The biosimilar of infliximab, CT-P13, has recently been shown
      to be equivalent to infliximab in both efficacy and safety in the treatment of
      rheumatologic diseases. However, no data are available with respect to the drug's
      efficacy in patients with inflammatory bowel disease (IBD). We aimed to assess
      the efficacy and safety of CT-P13 in IBD patients METHODS: This was a
      retrospective multicenter study including both anti-tumor necrosis factor (TNF)
      naive patients and patients who switched from the biologic originator to CT-P13.
      RESULTS: In anti-TNF naive Crohn's disease (CD) patients (n = 32), clinical
      response and remission rates were 90.6% and 68.8% at week 2, 90.6% and 84.4% at
      week 8, 95.5% and 77.3% at week 30, and 87.5% and 75.0% at week 54, respectively.
      In anti-TNF naive ulcerative colitis (UC) patients (n = 42), clinical response
      and remission rates were 76.2% and 19.0% at week 2, 81.0% and 38.1% at week 8,
      91.3% and 47.8% at week 30, and 100% and 50.0% at week 54, respectively, while
      mucosal healing rates were 58.3% at week 8, 66.7% at week 30, and 66.7% at week
      54. The efficacy of CT-P13 was maintained in 92.6% (25/27) of CD patients and in
      66.7% (6/9) of UC patients after switching from its originator. Adverse events
      related to CT-P13 occurred in 11.8% of UC patients. CONCLUSIONS: CT-P13 appears
      to have comparable efficacy, safety, and interchangeability with its originator
      in the treatment of IBD. Further prospective studies with long-term follow-up
      periods will be needed to confirm the biosimilarity of CT-P13.

PMID- 25974250
TI  - Delivery of a mucin domain enriched in cysteine residues strengthens the
      intestinal mucous barrier.
AB  - A weakening of the gut mucous barrier permits an increase in the access of
      intestinal luminal contents to the epithelial cells, which will trigger the
      inflammatory response. In inflammatory bowel diseases, there is an inappropriate
      and ongoing activation of the immune system, possibly because the intestinal
      mucus is less protective against the endogenous microflora. General strategies
      aimed at improving the protection of the intestinal epithelium are still missing.
      We generated a transgenic mouse that secreted a molecule consisting of 12
      consecutive copies of a mucin domain into its intestinal mucus, which is believed
      to modify the mucus layer by establishing reversible interactions. We showed that
      the mucus gel was more robust and that mucin O-glycosylation was altered.
      Notably, the gut epithelium of transgenic mice housed a greater abundance of
      beneficial Lactobacillus spp. These modifications were associated with a reduced
      susceptibility of transgenic mice to chemically induced colitis. Furthermore,
      transgenic mice cleared faster Citrobacter rodentium bacteria which were orally
      given and mice were more protected against bacterial translocation induced by
      gavage with adherent-invasive Escherichia coli. Our data show that delivering the
      mucin CYS domain into the gut lumen strengthens the intestinal mucus blanket
      which is impaired in inflammatory bowel diseases. 

PMID- 25974253
TI  - Trifluoromethyl-substituted sulfonium ylide: Rh-catalyzed carbenoid addition to
      trifluoromethylthioether.
AB  - A highly efficient Rh-catalyzed carbenoid addition to trifluoromethylthioether
      for the formation of trifluoromethyl-substituted sulfonium ylide is described.
      The trifluoromethyl-substituted sulfonium ylide can act as an electrophilic
      trifluoromethylation reagent, as demonstrated by trifluoromethylation of beta
      ketoesters and aryl iodides. 

PMID- 25974254
TI  - Stereoselective Wittig Olefination as a Macrocyclization Tool. Synthesis of Large
      Carbazolophanes.
AB  - Z-Selective Wittig olefination was applied to the synthesis of large
      carbazolophanes containing up to eight heteroaromatic subunits. A number of
      strategies were devised and tested, showing that cyclooligomerization yields can
      be significantly improved by using one-component schemes involving
      heterobifunctional reactants. [4]- and [6]Carbazolophanes were characterized in
      the solid state, revealing compact, highly folded structures. Electronic and
      steric effects of substitution and chain length on the Wittig olefination rates
      and Z-selectivities were explored theoretically using DFT calculations. 

PMID- 25974252
TI  - Deletion of Protein Tyrosine Phosphatase 1B (PTP1B) Enhances Endothelial
      Cyclooxygenase 2 Expression and Protects Mice from Type 1 Diabetes-Induced
      Endothelial Dysfunction.
AB  - Protein tyrosine phosphatase 1B (PTP1B) dephosphorylates receptors tyrosine
      kinase and acts as a molecular brake on insulin signaling pathway. Conditions of
      metabolic dysfunction increase PTP1B, when deletion of PTP1B protects against
      metabolic disorders by increasing insulin signaling. Although vascular insulin
      signaling contributes to the control of glucose disposal, little is known
      regarding the direct role of PTP1B in the control of endothelial function. We
      hypothesized that metabolic dysfunctions increase PTP1B expression in endothelial
      cells and that PTP1B deletion prevents endothelial dysfunction in situation of
      diminished insulin secretion. Type I diabetes (T1DM) was induced in wild-type
      (WT) and PTP1B-deficient mice (KO) with streptozotocin (STZ) injection. After 28
      days of T1DM, KO mice exhibited a similar reduction in body weight and plasma
      insulin levels and a comparable increase in glycemia (WT: 384 +/- 20 vs. Ko: 432
      +/- 29 mg/dL), cholesterol and triglycerides, as WT mice. T1DM increased PTP1B
      expression and impaired endothelial NO-dependent relaxation, in mouse aorta.
      PTP1B deletion did not affect baseline endothelial function, but preserved
      endothelium-dependent relaxation, in T1DM mice. NO synthase inhibition with L
      NAME abolished endothelial relaxation in control and T1DM WT mice, whereas L-NAME
      and the cyclooxygenases inhibitor indomethacin were required to abolish
      endothelium relaxation in T1DM KO mice. PTP1B deletion increased COX-2 expression
      and PGI2 levels, in mouse aorta and plasma respectively, in T1DM mice. In
      parallel, simulation of diabetic conditions increased PTP1B expression and
      knockdown of PTP1B increased COX-2 but not COX-1 expression, in primary human
      aortic endothelial cells. Taken together these data indicate that deletion of
      PTP1B protected endothelial function by compensating the reduction in NO
      bioavailability by increasing COX-2-mediated release of the vasodilator
      prostanoid PGI2, in T1DM mice.

PMID- 25974255
TI  - Systematic review of cardiovascular disease and cardiovascular death in patients
      with a small abdominal aortic aneurysm.
AB  - BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has reduced the rate of
      AAA rupture. However, cardiovascular disease is still a major cause of death in
      men with an AAA. The aim of this study was to assess cardiovascular risk in
      patients with a small AAA. METHODS: Standard PRISMA guidelines were followed.
      Analysis was performed of studies reporting cardiovascular outcomes in patients
      with a small AAA (30-54 mm). Weighted metaregression was performed for
      cardiovascular death in patients with a small AAA, and the prevalence of
      cardiovascular disease was reviewed. RESULTS: Twenty-one articles were identified
      describing patients with an AAA, and the prevalence of, and death from,
      cardiovascular disease. Ten of these reported cardiovascular death rates in
      patients with a small AAA. Some 2323 patients with a small AAA were identified;
      335 cardiovascular deaths occurred, of which 37 were due to AAA rupture.
      Metaregression demonstrated that the risk of cardiovascular death was 3.0 (95 per
      cent c.i. 1.7 to 4.3) per cent per year in patients with a small AAA (R(2) =
      0.902, P < 0.001). The prevalence of ischaemic heart disease (44.9 per cent),
      myocardial infarction (26.8 per cent), heart failure (4.4 per cent) and stroke
      (14.0 per cent) was also high in these patients. CONCLUSION: The risk of
      cardiovascular death in patients with a small AAA is high and increases by
      approximately 3 per cent each year after diagnosis. Patients with a small AAA
      have a high prevalence of cardiovascular disease. Patients a small AAA should be
      considered for lifestyle modifications and secondary cardiovascular protection.

PMID- 25974256
TI  - Cultural relativism: maintenance of genomic imprints in pluripotent stem cell
      culture systems.
AB  - Pluripotent stem cells (PSCs) in culture have become a widely used model for
      studying events occurring during mammalian development; they also present an
      exciting avenue for therapeutics. However, compared to their in vivo
      counterparts, cultured PSC derivatives have unique properties, and it is well
      established that their epigenome is sensitive to medium composition. Here we
      review the specific effects on genomic imprints in various PSC types and culture
      systems. Imprinted gene regulation is developmentally important, and imprinting
      defects have been associated with several human diseases. Therefore, imprint
      abnormalities in PSCs may have considerable consequences for downstream
      applications. 

PMID- 25974257
TI  - The Gender-Dependent Association between Obesity and Age-Related Cataracts in
      Middle-Aged Korean Adults.
AB  - The aim of this study was to investigate the association of central and abdominal
      obesity with the prevalence of cataracts in a middle-aged Korean population. This
      retrospective cross-sectional study was based on the data collected from the
      Korea National Health and Nutrition Examination Survey 2008-2009, in which 4,914
      subjects were examined. Ophthalmological examinations were performed to determine
      the presence of a nuclear, cortical, or posterior subcapsular cataract. Both
      general obesity (a body mass index >=25 kg/m2) and abdominal obesity (a waist
      circumference >=90 cm for men and >=80 cm for women) were significantly
      associated with the occurrence of cataracts among middle-aged women [adjusted
      odds ratio (aOR), 1.32; 95% confidence interval (CI), 1.03-1.69; and aOR, 1.40;
      95% CI, 1.06-1.85, respectively], while abdominal obesity was significantly
      inversely associated with the occurrence of cataracts among middle-aged men (aOR,
      0.76; 95% CI, 0.58-1.01; and aOR, 0.66; 95% CI, 0.49-0.89, respectively). We
      report a difference in the association between obesity and the prevalence of
      cataracts based on gender. 

PMID- 25974258
TI  - Avulsion fracture of anterior inferior iliac spine complicated by hypertrophic
      malunion causing femoroacetabular impingement: Case report.
AB  - INTRODUCTION: Avulsion fractures of the anterior inferior iliac spine are
      uncommon and such injuries are caused by the sudden forceful contraction of the
      straight head of rectus femoris muscle while the hip is hyperextended and the
      knee is flexed. CASE PRESENTATION: This case report describes the condition of 17
      year old male footballer who complained of pain in the right groin for duration
      of 2 years after being involved in forceful sport activity. Detailed history,
      clinical examination, X-rays and CT scan revealed hypertrophic malunion of
      avulsion fracture of anterior inferior iliac spine causing an extra-articular
      type of femoroacetabular impingement. The patient was surgically treated when
      conservative management was unsuccessful. DISCUSSION: This is the first case of
      hypertrophic malunion of avulsion fracture of anterior inferior iliac spine with
      femoroacetabular impingement that has been recognized in Qatar. The patient was
      surgically treated in order to relieve symptoms and avoid osteoarthritis.
      CONCLUSION: Malunited avulsion fracture of anterior inferior iliac spine can
      cause extra-articular femoroacetabular impingement.

PMID- 25974259
TI  - The successful use of dronabinol for failure to thrive secondary to intestinal
      dysmotility.
AB  - INTRODUCTION: Symptoms of severe intestinal dysmotility decrease patients'
      quality of life and may prevent them from sustaining adequate oral intake.
      Dronabinol is a synthetic cannabinoid that is labeled for use in AIDS-related
      anorexia and chemotherapy-associated nausea and vomiting that has additional
      efficacy in patients with other etiologies of nausea, vomiting, and anorexia.
      PRESENTATION OF CASE: We present a 58-year-old female with a history of nausea,
      vomiting, abdominal pain, and inability to maintain oral intake after multiple
      laparotomies for ectopic pregnancy, recurrent caecal volvulus, and cholecystitis.
      After eight years of unsuccessful trials of medicines, dietary modifications, and
      a partial colectomy, she began a trial of dronabinol, which caused almost
      complete remission of her symptoms. When this medication was discontinued by her
      payer, she was unable to maintain oral intake and therefore, was admitted to the
      hospital for fluid resuscitation and resumption of dronabinol. DISCUSSION: The
      use of dronabinol in this patient with severe intestinal dysmotility allowed her
      to maintain her nutritional status orally and obviated the need for enteral or
      parenteral feeding. Unfortunately, it was not covered by her insurance company
      for this indication. CONCLUSION: Dronabinol has the potential to improve quality
      of life for patients beyond those undergoing chemotherapy or suffering from AIDS.
      Lack of access to this medicine for patients with intestinal dysmotility after
      all other modalities have been tried can lead to morbid and expensive
      complications, such as inpatient admission and surgery for enteral access.

PMID- 25974260
TI  - PHACES syndrome: Diode laser photocoagulation of intraoral hemangiomas in six
      young patients.
AB  - INTRODUCTION: The acronym PHACES describes the association of posterior fossa
      malformations, facial hemangiomas, arterial anomalies (cardiovascular or
      cerebrovascular), coarctation of the aorta and cardiac defects, eye
      abnormalities, and sternal or ventral defects. In this study we report on 6
      patients affected by the PHACES syndrome and showing 34 intraoral hemangiomas
      (IH), treated by diode laser photocoagulation (DLP). CASE PRESENTATION: IH
      appeared as red-bluish soft masses, smooth or lobulated, from a few millimetre to
      several centimetres in size, covered by intact mucosa and blanching on pressure.
      IHs were treated by DLP with 320MUm fibres at a wavelength of 800+/-10nm. The
      diode laser techniques applied were: Transmucosal DLP (DLTP), a no-contact
      technique in which laser energy is delivered by a flexible optic quartz fiber,
      which is kept 2-3mm apart from the lesion, and Intralesional DLP (DLIP), in which
      the fibre is introduced into the lesion through a transmucosal access. DLTP was
      used for 20 flat, superficial IHs and, after a variable number of laser sessions
      (average=3) depending on the size of the lesion, 65% completely regressed, while
      in the remaining 35% shrinkage of the lesion was achieved with minor and few
      complications. The remaining 14 deep/multi-lobulated IHs were treated by DLIP,
      resulting in complete regression of 79% of them. CONCLUSIONS: DLP techniques are
      an effective and minimally invasive procedure for IH in patients with PHACES, in
      consideration of the multiple lesions to treat, of the necessity of multiple
      interventions and the higher compliance of the patients.

PMID- 25974261
TI  - What is the role of a case manager in community aged care? A qualitative study in
      Australia.
AB  - This study aimed to explore the perceptions of case managers about their roles in
      providing community aged care in Australia. Purposeful sampling was used and 33
      qualitative semi-structured interviews with 47 participants were conducted.
      Participants were drawn from a list of all case managers working in aged care
      organisations that provided publicly funded case-managed community aged care
      programmes in the State of Victoria, Australia. Participant selection criteria
      included age, gender, job titles, professional backgrounds, practice locations,
      organisational attributes and organisational size. Data collection was
      implemented between September 2012 and March 2013. Thematic analysis was
      performed. Participants believed that case managers performed diverse roles based
      on clients' needs. They also articulated 16 important roles of case managers,
      including advisors, advocates, carers, communicators, co-ordinators, educators,
      empowering clients, engaging clients and families, liaising with people, managing
      budgets, navigators, negotiators, networking with people, facilitators, problem
      solvers and supporters. However, they were concerned about brokers, mediators and
      counsellors in terms of the terminology or case managers' willingness to perform
      these roles. Moreover, they perceived that neither gatekeepers nor direct service
      provision was case managers' role. The findings of this study suggest that case
      managers working in community aged care sectors may be more effective if they
      practised the 16 roles aforementioned. With the value of helping rather than
      obstructing clients to access services, they may not act as gatekeepers. In
      addition, they may not provide services directly as opposed to their peers
      working in medical care settings. The findings will also assist organisations to
      design job descriptions specifying case managers' roles and associated job
      responsibilities. Clear job descriptions will further benefit the organisations
      in staff recruitment, orientation and ongoing development, as well as facilitate
      case managers to set professional boundaries in the delivery of case management
      interventions to their clients.

PMID- 25974262
TI  - Plasminogen activator inhibitor-1 as regulator of tumor-initiating cell
      properties in head and neck cancers.
AB  - BACKGROUND: The existence of tumor-initiating cells (TICs) has been described in
      head and neck cancers. Plasminogen activator inhibitor-1 (PAI-1) has been
      demonstrated to act as a prognostic factor in head and neck cancers. METHODS:
      Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, and PAI-1-specific siRNA
      were used to examine the role of PAI-1 in the self-renewal property of head and
      neck cancer-TICs by tumorsphere formation. Western blot, real-time polymerase
      chain reaction, and luciferase-based reporter assay were used to study the effect
      of PAI-039 in the sex-determining region Y-box 2 (Sox2) expression. RESULTS: PAI
      039 suppressed the self-renewal capability of head and neck cancer-TICs derived
      from head and neck cancer cell lines through the inhibition of Sox2 expression.
      PAI-039 decreased the activity of the core promoter and the enhancer of the Sox2
      gene in head and neck cancer-TICs. Knockdown of PAI-1 expression also inhibited
      self-renewal and radioresistance properties of head and neck cancer-TICs.
      CONCLUSION: The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and
      neck cancer-TICs within head and neck cancer cell lines through the
      downregulation of Sox2. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E895-E904,
      2016.

PMID- 25974263
TI  - The Prevalence and Types of Glaucoma in an Urban Chinese Population: The
      Singapore Chinese Eye Study.
AB  - IMPORTANCE: Glaucoma represents a major public health challenge in an aging
      population. The Tanjong Pagar Eye Study reported the prevalence and risk factors
      of glaucoma in a Singapore Chinese population in 1997, which established the
      higher rates of blindness in this population. OBJECTIVES: To determine the
      prevalence and associated risk factors for glaucoma among Chinese adults in
      Singapore and to compare the results with those of the 1997 study. DESIGN,
      SETTING, AND PARTICIPANTS: In a population-based survey of 4605 eligible
      individuals, we selected 3353 Chinese adults 40 years or older from the
      southwestern part of Singapore. Participants underwent examination at a single
      tertiary care research institute from February 9, 2009, through December 19,
      2011. EXPOSURES: All participants underwent slitlamp ophthalmic examination,
      applanation tonometry, measurement of central corneal thickness, gonioscopy, and
      a dilated fundus examination. MAIN OUTCOMES AND MEASURES: Glaucoma as defined by
      the International Society of Geographical and Epidemiological Ophthalmology
      guidelines and age-standardized prevalence estimates computed as per the 2010
      Singapore Chinese census. Blindness was defined as logMAR visual acuity of 1.00
      (Snellen equivalent, 20/200 or worse). RESULTS: Of the 3353 respondents, 134
      (4.0%) had glaucoma, including primary open-angle glaucoma (POAG) in 57 (1.7%),
      primary angle-closure glaucoma (PACG) in 49 (1.5%), and secondary glaucoma in 28
      (0.8%). The age-standardized prevalence (95% CI) of glaucoma was 3.2% (2.7%
      3.9%); POAG, 1.4% (1.1%-1.9%); and PACG, 1.2% (0.9%-1.6%). In a multivariate
      model, POAG was associated with being older and male and having a higher
      intraocular pressure. Of the 134 participants with glaucoma, 114 (85.1%; 95% CI,
      78.1%-90.1%) were not aware of their diagnosis. Prevalence (95% CI) of blindness
      caused by secondary glaucoma was 14.3% (5.7%-31.5%), followed by 10.2% (4.4%
      21.8%) for PACG and 8.8% (3.8%-18.9%) for POAG. We could not identify a
      difference in the prevalence of glaucoma compared with the 3.2% reported in 1997
      (difference, -0.04%; 95% CI, -1.2 to 1.2; P = .97). CONCLUSIONS AND RELEVANCE:
      The prevalence of glaucoma among Singapore Chinese likely ranges from 2.7% to
      3.9%, with secondary glaucoma being the most visually debilitating type. We could
      not identify a difference compared with previous studies approximately 12 years
      earlier. We report a high proportion of previously undiagnosed disease,
      suggesting the need to increase public awareness of this potentially blinding
      condition.

PMID- 25974264
TI  - Correction: Gene Expression Profiling Identifies Molecular Pathways Associated
      with Collagen VI Deficiency and Provides Novel Therapeutic Targets.

PMID- 25974265
TI  - Novel Furin Inhibitors with Potent Anti-infectious Activity.
AB  - New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3
      position were synthesized. The most potent compound 4-guanidinomethyl
      phenylacteyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) inhibits furin with a Ki
      value of 5.5 pM. The derivatives also strongly inhibit PC1/3, whereas PC2 is less
      affected. Selected inhibitors were tested in cell culture for antibacterial and
      antiviral activity against infectious agents known to be dependent on furin
      activity. A significant protective effect against anthrax and diphtheria toxin
      was observed in the presence of the furin inhibitors. Furthermore, the spread of
      the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of
      canine distemper virus was strongly inhibited. Inhibitor MI-1148 was crystallized
      in complex with human furin. Its N-terminal guanidinomethyl group in the para
      position of the P5 phenyl ring occupies the same position as that found
      previously for a structurally related inhibitor containing this substitution in
      the meta position, thereby maintaining all of the important P5 interactions. Our
      results confirm that the inhibition of furin is a promising strategy for a short
      term treatment of acute infectious diseases.

PMID- 25974266
TI  - Sequential spasm provocation tests might overcome a limitation of the standard
      spasm provocation tests.
AB  - OBJECTIVE: We examined the clinical usefulness of sequential spasm provocation
      tests as follows: first, acetylcholine (ACh) test, second, ergonovine (ER) test,
      and finally, the ACh test following the ER test. PATIENTS AND METHODS: We
      performed the ACh and ER tests in 461 patients (294 men, 64.4+/-11.3 years of
      age) during a 23-year period. In addition, we administered an intracoronary
      injection of ACh after the ER tests in 240 patients. First, ACh [right coronary
      artery (RCA): 20/50/(80) MUg, left coronary artery (LCA): 20/50/100/(200) MUg]
      was administered incrementally over 20 s. Second, ER (RCA: 40 MUg, LCA: 64 MUg)
      was administered over 2-4 min. If a provoked spasm did not occur, we administered
      an intracoronary injection of ACh (50/80 MUg into the RCA and 100/200 MUg into
      the LCA) just after the ER tests. A positive spasm was defined as more than 99%
      transient luminal narrowing. RESULTS: A positive spasm was observed in 221
      (47.9%) patients including 181 ACh-positive (39.3%) and 119 ER-positive (25.8%)
      patients by the ACh or ER tests. In the 240 patients with a negative spasm in the
      ACh and ER tests, 48 (10.4%) patients developed provoked spasms on adding ACh
      after the ER test. The distributions of various cardiac disorders and provoked
      spasm vessels were similar among the three positive groups. Focal spasm was
      frequently observed in the ER-positive group, whereas diffuse spasm was
      frequently obtained in the ACh-positive group and by adding ACh after ER in the
      positive group. No major complications were recognized during the sequential
      spasm provocation tests. CONCLUSION: Sequential spasm provocation tests might
      overcome a limitation of standard spasm provocation tests.

PMID- 25974267
TI  - Out-of-hospital cardiac arrest: defining the role of coronary angiography and
      intervention.
AB  - Targeted temperature management and early coronary angiography have become the
      standard of care for postcardiac arrest patients remaining comatose and with ST
      segment elevation on the ECG. Less clear is the optimal approach for similar
      patients without ST-segment elevation on the postresuscitation ECG. However,
      current data from nonrandomized cohort studies suggest that many of these
      patients also benefit from an aggressive approach to postresuscitation care.
      Recent reports of increased stent thrombosis in the postarrest population need
      further exploration. 

PMID- 25974268
TI  - Effect of percutaneous coronary intervention on heart rate recovery in patients
      with coronary artery disease.
AB  - OBJECTIVE: This study aimed to investigate the effect of percutaneous coronary
      intervention (PCI) on heart rate recovery (HRR) in patients with angiographically
      defined coronary artery disease, and to search for a noninvasive method for
      evaluating the effect of revascularization. METHODS: From June 2012 to July 2013,
      56 consecutive male patients with coronary artery disease were enrolled in the
      PCI group. Correspondingly, in the control group there were 56 consecutive male
      patients with chest pain but a normal coronary artery verified by angiography.
      The exercise treadmill test was performed 3 days before and 7 days after
      intervention in the PCI group, and 3 days before angiography in the control
      group. RESULTS: The peak heart rate, metabolic equivalents, and the Duke score
      were notably lower in the PCI group before intervention compared with the control
      group (P<0.01). In contrast, preintervention ST depression in the PCI group was
      significantly higher than that in the control group (P<0.01). Preintervention HRR
      values from 1 to 6 min were much lower in the PCI group compared with the control
      group (P<0.01). HRR values from 1 to 6 min in the PCI group post intervention
      increased significantly compared with preintervention HRR values (P<0.01),
      especially at 3, 4, 5, and 6 min. HRR values at 1, 2, and 3 min increased sharply
      post intervention. CONCLUSION: Successful revascularization through PCI could
      improve HRR in patients with major coronary artery involvement. Moreover, HRR
      measurement may be used as a noninvasive method for evaluating the effect of
      revascularization.

PMID- 25974270
TI  - Indian plant germplasm on the global platter: an analysis.
AB  - Food security is a global concern amongst scientists, researchers and policy
      makers. No country is self-sufficient to address food security issues
      independently as almost all countries are inter-dependent for availability of
      plant genetic resources (PGR) in their national crop improvement programmes.
      Consultative Group of International Agricultural Research (CGIAR; in short CG)
      centres play an important role in conserving and distributing PGR through their
      genebanks. CG genebanks assembled the germplasm through collecting missions and
      acquisition the same from national genebanks of other countries. Using the
      Genesys Global Portal on Plant Genetic Resources, the World Information and Early
      Warning System (WIEWS) on Plant Genetic Resources for Food and Agriculture and
      other relevant databases, we analysed the conservation status of Indian-origin
      PGR accessions (both cultivated and wild forms possessed by India) in CG
      genebanks and other national genebanks, including the United States Department of
      Agriculture (USDA) genebanks, which can be considered as an indicator of Indian
      contribution to the global germplasm collection. A total of 28,027,770 accessions
      are being conserved world-wide by 446 organizations represented in Genesys; of
      these, 3.78% (100,607) are Indian-origin accessions. Similarly, 62,920 Indian
      origin accessions (8.73%) have been conserved in CG genebanks which are
      accessible to the global research community for utilization in their respective
      crop improvement programmes. A total of 60 genebanks including 11 CG genebanks
      have deposited 824,625 accessions of PGR in the Svalbard Global Seed Vault (SGSV)
      as safety duplicates; the average number of accessions deposited by each genebank
      is 13,744, and amongst them there are 66,339 Indian-origin accessions. In
      principle, India has contributed 4.85 times the number of germplasm accessions to
      SGSV, in comparison to the mean value (13,744) of any individual genebank
      including CG genebanks. More importantly, about 50% of the Indian-origin
      accessions deposited in SGSV are traditional varieties or landraces with defined
      traits which form the backbone of any crop gene pool. This paper is also
      attempting to correlate the global data on Indian-origin germplasm with the
      national germplasm export profile. The analysis from this paper is discussed with
      the perspective of possible implications in the access and benefit sharing regime
      of both the International Treaty on Plant Genetic Resources for Food and
      Agriculture and the newly enforced Nagoya Protocol under the Convention on
      Biological Diversity. 

PMID- 25974269
TI  - Different Roles of COMT and HTR2A Genotypes in Working Memory Subprocesses.
AB  - Working memory is linked to the functions of the frontal areas, in which neural
      activity is mediated by dopaminergic and serotonergic tones. However, there is no
      consensus regarding how the dopaminergic and serotonergic systems influence
      working memory subprocesses. The present study used an imaging genetics approach
      to examine the interaction between neurochemical functions and working memory
      performance. We focused on functional polymorphisms of the catechol-O
      methyltransferase (COMT) Val(158)Met and serotonin 2A receptor (HTR2A) -1438G/A
      genes, and devised a delayed recognition task to isolate the encoding, retention,
      and retrieval processes for visual information. The COMT genotypes affected
      recognition accuracy, whereas the HTR2A genotypes were associated with
      recognition response times. Activations specifically related to working memory
      were found in the right frontal and parietal areas, such as the middle frontal
      gyrus (MFG), inferior frontal gyrus (IFG), anterior cingulate cortex (ACC), and
      inferior parietal lobule (IPL). MFG and ACC/IPL activations were sensitive to
      differences between the COMT genotypes and between the HTR2A genotypes,
      respectively. Structural equation modeling demonstrated that stronger
      connectivity in the ACC-MFG and ACC-IFG networks is related to better task
      performance. The behavioral and fMRI results suggest that the dopaminergic and
      serotonergic systems play different roles in the working memory subprocesses and
      modulate closer cooperation between lateral and medial frontal activations.

PMID- 25974271
TI  - Body-related sport and exercise motives and disturbed eating attitudes and
      behaviours in adolescents.
AB  - Motives underlying sport and exercise involvement have recently been hypothesized
      as potential factors influencing the positive association between
      sports/exercises involvement and disturbed eating attitudes and behaviours (DEAB)
      among adolescents. Nevertheless, very few studies have examined this hypothesis
      or the moderating role of gender, context of practice, performance levels and
      sport type on these relationships. In this study, these questions were addressed
      among 168 male and 167 female French adolescents involved in various types,
      contexts and performance levels of sport and exercise. Participants were asked to
      indicate their main motives for involvement in sport practice and to self-report
      DEAB (generic DEAB, vomiting-purging behaviours, and eating-related control) on a
      French adaptation of the Eating Attitudes Test-26. The results shared positive
      associations between body-related sport and exercise motives and most of the DEAB
      subscales. Furthermore, they show that the relationship between body-related
      sport and exercise motives and Vomiting-Purging Behaviours differs according to
      involvement in individual and competitive sports and exercises.

PMID- 25974272
TI  - Residual water in ionic liquids: clustered or dissociated?
AB  - How do residual water molecules in ionic liquids (ILs) interact with themselves,
      as well as with the ions? This question is crucial in understanding why the
      physical properties of ILs--and chemical reactions performed in them--are
      strongly affected by the residual water content. There have been three
      conflicting hypotheses regarding the structure and behaviour of the residual
      water: (i) water molecules are separated from one another, while interacting
      strongly with the ions, and dispersed throughout the medium; (ii) water molecules
      self-associate or form clusters in the ILs; (iii) residual water weakens ion-ion
      interactions. A satisfactory resolution of these conflicting suggestions has been
      hindered by the complexity and long range of the interactions in the water-IL
      mixture and by the often profound differences in physical structure between
      various different ILs. Here we present a route to resolve this question through a
      combination of a statistical thermodynamic theory (Kirkwood-Buff theory) with
      density and osmotic data from the literature. The structure of water-IL mixtures
      is shown to be water content dependent; at the lowest measured water
      concentration, strong water-IL interaction and water-water separation are
      observed in accordance to (i), whereas water in a more hydrophobic IL environment
      seems to self-associate at moderately low water concentrations, in accordance
      with (ii).

PMID- 25974273
TI  - Mechanistic insights into bicyclic guanidine-catalyzed reactions from microscopic
      and macroscopic perspectives.
AB  - Chiral bicyclic guanidine can act as an efficient chiral Bronsted base catalyst
      in enantioselective reactions, delivering good yields with high
      enantioselectivities. There is interest in understanding the detailed mechanisms
      of these guanidine-catalyzed reactions. Herein, we performed a detailed kinetic
      study of three different types of chiral bicyclic guanidine-catalyzed reactions,
      determining the bifunctionality of our guanidine catalyst. Although these three
      reactions share a similar catalytic cycle, their intrinsic kinetic behaviors are
      significantly different from each other because of the difference in the rate
      determining step. The calculated theoretical rate expression for each reaction,
      as a result of the mechanism elucidated with density functional theory
      calculations, agrees well with the respective experimentally observed rate
      equation. 

PMID- 25974274
TI  - Unintended effects of reimbursement schedules in mental health care.
AB  - We evaluate the introduction of a reimbursement schedule for self-employed mental
      health care providers in the Netherlands in 2008. The reimbursement schedule
      follows a discontinuous discrete step function-once the provider has passed a
      treatment duration threshold the fee is flat until a next threshold is reached.
      We use administrative mental health care data of the total Dutch population from
      2008 to 2010. We find an "efficiency" effect: on the flat part of the fee
      schedule providers reduce treatment duration by 2 to 7% compared to a control
      group. However, we also find unintended effects: providers treat patients longer
      to reach a next threshold and obtain a higher fee. The data shows gaps and
      bunches in the distribution function of treatment durations, just before and
      after a threshold. About 11 to 13% of treatments are shifted over a next
      threshold, resulting in a cost increase of approximately 7 to 9%. 

PMID- 25974275
TI  - Pathophysiology and Etiology of Nerve Injury Following Peripheral Nerve Blockade.
AB  - This review synthesizes anatomical, anesthetic, surgical, and patient factors
      that may contribute to neurologic complications associated with peripheral nerve
      blockade. Peripheral nerves have anatomical features unique to a given location
      that may influence risk of injury. Peripheral nerve blockade-related peripheral
      nerve injury (PNI) is most severe with intrafascicular injection. Surgery and its
      associated requirements such as positioning and tourniquet have specific risks.
      Patients with preexisting neuropathy may be at an increased risk of postoperative
      neurologic dysfunction. Distinguishing potential causes of PNI require clinical
      assessment and investigation; a definitive diagnosis, however, is not always
      possible. Fortunately, most postoperative neurologic dysfunction appears to
      resolve with time, and the incidence of serious long-term nerve injury directly
      attributable to peripheral nerve blockade is relatively uncommon. Nonetheless,
      despite the use of ultrasound guidance, the risk of block-related PNI remains
      unchanged. WHAT'S NEW: Since the 2008 Practice Advisory, new information has been
      published, furthering our understanding of the microanatomy of peripheral nerves,
      mechanisms of peripheral nerve injection injury, toxicity of local anesthetics,
      the etiology of and monitoring methods, and technologies that may decrease the
      risk of nerve block-related peripheral nerve injury.

PMID- 25974276
TI  - Worsening of Neurologic Symptoms After Spinal Anesthesia in Two Patients With
      Spinal Stenosis.
AB  - OBJECTIVE: Spinal stenosis has been proposed as a previously unrecognized risk
      factor for neurologic complications after neuraxial techniques. CASE REPORT: We
      report progression of neurologic symptoms after spinal anesthesia in 2 patients
      with preexisting spinal stenosis, characterized preoperatively solely by
      nonradicular back pain. One patient had complete resolution of his proximal lower
      extremity weakness/numbness within 48 hours. In the second patient, the pain
      became severe and disabling, requiring surgical decompression. CONCLUSIONS: We
      conclude that, until the relative contribution of patient and surgical (eg,
      positioning, retractors, hypotension) factors is known, the decision to perform
      neuraxial blockade in patients with severe symptoms of neuroclaudication or
      recently progressive symptomatic spinal stenosis should be made cautiously.
      Avoidance of spinal anesthesia is suggested for any procedure with prolonged
      lordotic positioning or any position that might cause a compromise of the spinal
      canal because subarachnoid block may contribute to any deterioration suffered by
      the patient.

PMID- 25974278
TI  - First-principle modelling of forsterite surface properties: Accuracy of methods
      and basis sets.
AB  - The seven main crystal surfaces of forsterite (Mg2 SiO4 ) were modeled using
      various Gaussian-type basis sets, and several formulations for the exchange
      correlation functional within the density functional theory (DFT). The recently
      developed pob-TZVP basis set provides the best results for all properties that
      are strongly dependent on the accuracy of the wavefunction. Convergence on the
      structure and on the basis set superposition error-corrected surface energy can
      be reached also with poorer basis sets. The effect of adopting different DFT
      functionals was assessed. All functionals give the same stability order for the
      various surfaces. Surfaces do not exhibit any major structural differences when
      optimized with different functionals, except for higher energy orientations where
      major rearrangements occur around the Mg sites at the surface or subsurface. When
      dispersions are not accounted for, all functionals provide similar surface
      energies. The inclusion of empirical dispersions raises the energy of all
      surfaces by a nearly systematic value proportional to the scaling factor s of the
      dispersion formulation. An estimation for the surface energy is provided through
      adopting C6 coefficients that are more suitable than the standard ones to
      describe O-O interactions in minerals. A 2 * 2 supercell of the most stable
      surface (010) was optimized. No surface reconstruction was observed. The
      resulting structure and surface energy show no difference with respect to those
      obtained when using the primitive cell. This result validates the (010) surface
      model here adopted, that will serve as a reference for future studies on
      adsorption and reactivity of water and carbon dioxide at this interface.

PMID- 25974277
TI  - Addition of Dexamethasone and Buprenorphine to Bupivacaine Sciatic Nerve Block: A
      Randomized Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: Sciatic nerve block provides analgesia after foot and
      ankle surgery, but block duration may be insufficient. We hypothesized that
      perineural dexamethasone and buprenorphine would reduce pain scores at 24 hours.
      METHODS: Ninety patients received ultrasound-guided sciatic (25 mL 0.25%
      bupivacaine) and adductor canal (10 mL 0.25% bupivacaine) blockade, with random
      assignment into 3 groups (30 patients per group): control blocks + intravenous
      (IV) dexamethasone (4 mg) (control); control blocks + IV buprenorphine (150 MUg)
      + IV dexamethasone (IV buprenorphine); and nerve blocks containing buprenorphine
      + dexamethasone (perineural). Patients received mepivacaine neuraxial anesthesia
      and postoperative oxycodone/acetaminophen, meloxicam, pregabalin, and
      ondansetron. Patients and assessors were blinded to group assignment. The primary
      outcome was pain with movement at 24 hours. RESULTS: There was no difference in
      pain with movement at 24 hours (median score, 0). However, the perineural group
      had longer block duration versus control (45.6 vs 30.0 hours). Perineural
      patients had lower scores for "worst pain" versus control (median, 0 vs 2). Both
      IV buprenorphine and perineural groups were less likely to use opioids on the day
      after surgery versus control (28.6%, 28.6%, and 60.7%, respectively). Nausea
      after IV buprenorphine (but not perineural buprenorphine) was severe, frequent,
      and bothersome. CONCLUSIONS: Pain scores were very low at 24 hours after surgery
      in the context of multimodal analgesia and were not improved by additives.
      However, perineural buprenorphine and dexamethasone prolonged block duration,
      reduced the worst pain experienced, and reduced opioid use. Intravenous
      buprenorphine caused troubling nausea and vomiting. Future research is needed to
      confirm and extend these observations.

PMID- 25974279
TI  - Kinetic studies of the reaction between pesticides and hydroxyl radical generated
      by laser flash photolysis.
AB  - BACKGROUND: Due to contamination of the environment by pesticides and their
      mishandling, there is the need for treatment of contaminated sites and correct
      disposal of materials containing them. Thus, studies with advanced oxidation
      processes are expanding and can determine the rate constant of the hydroxyl
      radical with organic compounds of great importance in environmental
      contamination. In this context, the use of laser flash photolysis has been shown
      to be viable for the determination of these constants. RESULTS: The reaction rate
      constants of different pesticides with HO(*) in degassed acetonitrile have been
      determined. They were 1.6 * 10(9)  M(-1)  s(-1), 0.6 * 10(9)  M(-1)  s(-1), 1.2 *
      10(9)  M(-1)  s(-1), 2.4 * 10(9)  M(-1)  s(-1) and 2.2 * 10(9)  M(-1)  s(-1) for
      the pesticides carbaryl, propoxur, fenoxycarb, ethoxysulfuron and chlorimuron
      ethyl, respectively. These values are about an order of magnitude smaller than
      the diffusion controlled rate and correlate with the relative rates of
      disappearance of the pesticides in the photo-Fenton reaction in water.
      CONCLUSION: The correlation of the relative rate constants determined by laser
      flash photolysis with the relative rates of photo-Fenton degradation of the
      pesticides is compelling evidence for the participation of the hydroxyl radical
      in the degradation of these pesticides in the latter system.

PMID- 25974280
TI  - Subsidence and human influences in mega deltas: The case of the Ganges
      Brahmaputra-Meghna.
AB  - Relative sea/land level changes are fundamental to people living in deltas. Net
      subsidence is complex and attributed to tectonics, compaction, sedimentation and
      anthropogenic causes. It can have severe impacts and needs to be quantified and
      where possible (for subsidence due to anthropogenic causes) avoided. For the
      highly populated Ganges-Brahmaputra-Meghna delta, a large range of net subsidence
      rates are described in the literature, yet the reasons behind this wide range of
      values are poorly understood. This paper documents and analyses rates of
      subsidence (for publications until 2014) and relates these findings to human
      influences (development). 205 point measurements of net subsidence were found,
      reported in 24 studies. Reported measurements were often repetitive in multiple
      journals, with some lacking detail as to precise location, cause and method,
      questioning reliability of the rate of subsidence. Rates differed by locality,
      methodology and period of measurement. Ten different measurement methods were
      recorded, with radio-carbon dating being the most common. Temporal and spatially,
      rates varied between -1.1mm/yr (i.e. uplift) and 43.8mm/yr. The overall mean
      reported rate was 5.6mm/yr, and the overall median 2.9 mm/yr, with 7.3mm/yr
      representing one standard deviation. These rates were reduced if inaccurate or
      vague records were omitted. The highest rates were recorded in the Sylhet
      Plateau, Dhaka and Kolkata. Highest rates were recorded in the last 1000 years,
      where the mean increased to 8.8mm/yr and a standard deviation of 7.5mm/yr. This
      could be partly due to shorter-term measurement records, or anthropogenic
      influence as multiple high rates are often found in urban settings. Continued
      development may cause rates to locally increase (e.g. due to groundwater
      abstraction and/or drainage). Improved monitoring is required over a wider area,
      to determine long-term trends, particularly as short-term records are highly
      variable. Focus in regions where wide spread development is occurring or is
      expected would be advantageous.

PMID- 25974282
TI  - Lung microbiota across age and disease stage in cystic fibrosis.
AB  - Understanding the significance of bacterial species that colonize and persist in
      cystic fibrosis (CF) airways requires a detailed examination of bacterial
      community structure across a broad range of age and disease stage. We used 16S
      ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients
      spanning a 60 year age range, including 76 pediatric samples from patients of age
      4-17, and a broad cross-section of disease status to identify features of
      bacterial community structure and their relationship to disease stage and age.
      The CF lung microbiota shows significant inter-individual variability in
      community structure, composition and diversity. The core microbiota consists of
      five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF
      associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and
      Achromobacter are less prevalent than core genera, but have a strong tendency to
      dominate the bacterial community when present. Community diversity and lung
      function are greatest in patients less than 10 years of age and lower in older
      age groups, plateauing at approximately age 25. Lower community diversity
      correlates with worse lung function in a multivariate regression model. Infection
      by Pseudomonas correlates with age-associated trends in community diversity and
      lung function. 

PMID- 25974281
TI  - When getting there is not enough: a nationwide cross-sectional study of 998
      maternal deaths and 1451 near-misses in public tertiary hospitals in a low-income
      country.
AB  - OBJECTIVE: To investigate the burden and causes of life-threatening maternal
      complications and the quality of emergency obstetric care in Nigerian public
      tertiary hospitals. DESIGN: Nationwide cross-sectional study. SETTING: Forty-two
      tertiary hospitals. POPULATION: Women admitted for pregnancy, childbirth and
      puerperal complications. METHODS: All cases of severe maternal outcome (SMO:
      maternal near-miss or maternal death) were prospectively identified using the WHO
      criteria over a 1-year period. MAIN OUTCOME MEASURES: Incidence and causes of
      SMO, health service events, case fatality rate, and mortality index (% of
      maternal death/SMO). RESULTS: Participating hospitals recorded 91 724 live births
      and 5910 stillbirths. A total of 2449 women had an SMO, including 1451 near
      misses and 998 maternal deaths (2.7, 1.6 and 1.1% of live births, respectively).
      The majority (91.8%) of SMO cases were admitted in critical condition. Leading
      causes of SMO were pre-eclampsia/eclampsia (23.4%) and postpartum haemorrhage
      (14.4%). The overall mortality index for life-threatening conditions was 40.8%.
      For all SMOs, the median time between diagnosis and critical intervention was 60
      minutes (IQR: 21-215 minutes) but in 21.9% of cases, it was over 4 hours. Late
      presentation (35.3%), lack of health insurance (17.5%) and non-availability of
      blood/blood products (12.7%) were the most frequent problems associated with
      deficiencies in care. CONCLUSIONS: Improving the chances of maternal survival
      would not only require timely application of life-saving interventions but also
      their safe, efficient and equitable use. Maternal mortality reduction strategies
      in Nigeria should address the deficiencies identified in tertiary hospital care
      and prioritise the prevention of severe complications at lower levels of care.
      TWEETABLE ABSTRACT: Of 998 maternal deaths and 1451 near-misses reported in a
      network of 42 Nigerian tertiary hospitals in 1 year.

PMID- 25974283
TI  - Weight-sparing effect of insulin detemir: a consequence of central nervous system
      mediated reduced energy intake?
AB  - Insulin therapy is often associated with adverse weight gain. This is
      attributable, at least in part, to changes in energy balance and insulin's
      anabolic effects. Adverse weight gain increases the risk of poor macrovascular
      outcomes in people with diabetes and should therefore be mitigated if possible.
      Clinical studies have shown that insulin detemir, a basal insulin analogue,
      exerts a unique weight-sparing effect compared with other basal insulins. To
      understand this property, several hypotheses have been proposed. These explore
      the interplay of efferent and afferent signals between the muscles, brain, liver,
      renal and adipose tissues in response to insulin detemir and comparator basal
      insulins. The following models have been proposed: insulin detemir may reduce
      food intake through direct or indirect effects on the central nervous system
      (CNS); it may have favourable actions on hepatic glucose metabolism through a
      selective effect on the liver, or it may influence fluid homeostasis through
      renal effects. Studies have consistently shown that insulin detemir reduces
      energy intake, and moreover, it is clear that this shift in energy balance is not
      a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct
      action, by indirect stimulation by peripheral mediators and/or via a more
      physiological counter-regulatory response to insulin through restoration of the
      hepatic-peripheral insulin gradient. Although the precise mechanism remains
      unclear, it is likely that the weight-sparing effect of insulin detemir can be
      explained by a combination of mechanisms. The evidence for each hypothesis is
      considered in this review. 

PMID- 25974284
TI  - Gonadal function and fertility after stem cell transplantation in childhood:
      comparison of a reduced intensity conditioning regimen containing melphalan with
      a myeloablative regimen containing busulfan.
AB  - The occurrence of late sequelae after myeloablative conditioning regimens for
      stem-cell transplantation (SCT) has prompted the introduction of reduced
      intensity chemotherapy (RIC) regimens in an attempt to reduce toxicity and spare
      fertility. We retrospectively evaluated gonadal function in survivors of SCT in
      childhood by comparing patients conditioned with a myeloablative regimen
      containing busulfan and cyclophosphamide (BuCy, N = 51, 28 boys) and a RIC
      regimen containing fludarabine and melphalan (FluMel, N = 40, 19 boys).
      Spontaneous puberty occurred in 56% of girls and 89% of boys after BuCy, whereas
      90% of females and all males in the FluMel group entered puberty spontaneously (P
      = 0.012). Significantly more females (61%) conditioned with BuCy required hormone
      replacement compared with the FluMel group (10.5%, P = 0.012). Females in the
      FluMel group took significantly longer to develop elevation of serum follicle
      stimulating hormone (FSH) concentrations (>10 iu/l) from the onset of puberty
      than females in the BuCy group (median 5.2 years vs. 2.7 years respectively, P =
      0.0135). In males no difference was noted between the two conditioning groups in
      time to FSH elevation (median 4 years in FluMel versus 6 years in BuCy). Whilst
      the two regimens have similar effects on the testis, ovarian function seems to be
      better preserved in females undergoing SCT with RIC. 

PMID- 25974285
TI  - Toward Repositioning Niclosamide for Antivirulence Therapy of Pseudomonas
      aeruginosa Lung Infections: Development of Inhalable Formulations through
      Nanosuspension Technology.
AB  - Inhaled antivirulence drugs are currently considered a promising therapeutic
      option to treat Pseudomonas aeruginosa lung infections in cystic fibrosis (CF).
      We have recently shown that the anthelmintic drug niclosamide (NCL) has strong
      quorum sensing (QS) inhibiting activity against P. aeruginosa and could be
      repurposed as an antivirulence drug. In this work, we developed dry powders
      containing NCL nanoparticles that can be reconstituted in saline solution to
      produce inhalable nanosuspensions. NCL nanoparticles were produced by high
      pressure homogenization (HPH) using polysorbate 20 or polysorbate 80 as
      stabilizers. After 20 cycles of HPH, all formulations showed similar properties
      in the form of needle-shape nanocrystals with a hydrodynamic diameter of
      approximately 450 nm and a zeta potential of -20 mV. Nanosuspensions stabilized
      with polysorbate 80 at 10% w/w to NCL (T80_10) showed an optimal solubility
      profile in simulated interstitial lung fluid. T80_10 was successfully dried into
      mannitol-based dry powder by spray drying. Dry powder (T80_10 DP) was
      reconstituted in saline solution and showed optimal in vitro aerosol performance.
      Both T80_10 and T80_10 DP were able to inhibit P. aeruginosa QS at NCL
      concentrations of 2.5-10 MUM. NCL, and these formulations did not significantly
      affect the viability of CF bronchial epithelial cells in vitro at
      microbiologically active concentrations (i.e., <=10 MUM). In vivo acute toxicity
      studies in rats confirmed no observable toxicity of the NCL T80_10 DP formulation
      upon intratracheal administration at a concentration 100-fold higher than the
      anti-QS activity concentration. These preliminary results suggest that NCL
      repurposed in the form of inhalable nanosuspensions has great potential for the
      local treatment of P. aeruginosa lung infections as in the case of CF patients. 

PMID- 25974286
TI  - Inhibition of Gallic Acid on the Growth and Biofilm Formation of Escherichia coli
      and Streptococcus mutans.
AB  - New strategies for biofilm inhibition are becoming highly necessary because of
      the concerns to synthetic additives. As gallic acid (GA) is a hydrolysated
      natural product of tannin in Chinese gall, this research studied the effects of
      GA on the growth and biofilm formation of bacteria (Escherichia coli [Gram
      negative] and Streptococcus mutans [Gram-positive]) under different conditions,
      such as nutrient levels, temperatures (25 and 37  degrees C) and incubation times
      (24 and 48 h). The minimum antimicrobial concentration of GA against the two
      pathogenic organisms was determined as 8 mg/mL. GA significantly affected the
      growth curves of both test strains at 25 and 37  degrees C. The nutrient level,
      temperature, and treatment time influenced the inhibition activity of GA on both
      growth and biofim formation of tested pathogens. The inhibition effect of GA on
      biofilm could be due to other factors in addition to the antibacterial effect.
      Overall, GA was most effective against cultures incubated at 37  degrees C for 24
      h and at 25  degrees C for 48 h in various concentrations of nutrients and in
      vegetable wash waters, which indicated the potential of GA as emergent sources of
      biofilm control products. 

PMID- 25974287
TI  - Randomized, Double-Blind, Crossover Trial of Amitriptyline for Analgesia in
      Painful HIV-Associated Sensory Neuropathy.
AB  - We conducted a randomized, double-blind, placebo-controlled, crossover study at a
      single center in South Africa, to ascertain whether amitriptyline is an effective
      analgesic for painful HIV-associated sensory neuropathy of moderate to severe
      intensity in: i) antiretroviral drug naive individuals, and ii) antiretroviral
      drug users. 124 HIV-infected participants (antiretroviral drug naive = 62,
      antiretroviral drug users = 62) who met the study criteria for painful HIV
      associated sensory neuropathy were randomized to once-daily oral amitriptyline
      (titrated to a median: interquartile range of 50: 25-50 mg) or placebo for six
      weeks, followed by a three-week washout period and subsequent treatment
      crossover. The primary outcome measure was change from baseline in worst pain
      intensity of the feet (measured by participant self-report using an 11-point
      numerical pain rating scale) after six weeks of treatment. 122 of 124
      participants completed all study visits and were included in the analysis of the
      primary outcome. In the antiretroviral drug-naive group (n = 61) there was no
      significant difference in the mean change in pain score from baseline after six
      weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3) vs.
      placebo: 2.8 (3.4)]. Similarly, there was no significant difference in the change
      in pain score after six weeks of treatment with placebo or amitriptyline in the
      antiretroviral drug-user group (n = 61) [amitriptyline: 2.7 (3.3) vs. placebo:
      2.1 (2.8)]. Controlling for period effects and treatment order effects did not
      alter the outcome of the analyses. Nor did analyzing the intention-to-treat
      cohort (missing data interpolated using baseline observation carried forward)
      alter the outcome of the analyses. In summary, amitriptyline, at the doses used
      here, was no more effective than an inactive placebo at reducing pain intensity
      in individuals with painful HIV-associated sensory neuropathy of moderate to
      severe intensity, irrespective of whether they were on antiretroviral therapy or
      not. TRIAL REGISTRATION: ISRCTN 54452526.

PMID- 25974288
TI  - Anti-adalimumab antibodies in juvenile idiopathic arthritis: frequent association
      with loss of response.
AB  - OBJECTIVES: We aimed to determine how loss of response (LOR) to adalimumab (ADA)
      in juvenile idiopathic arthritis (JIA) may be related to anti-ADA antibodies
      (AAA). METHOD: AAA and ADA levels were measured in 23 consecutive patients with
      JIA responding significantly to treatment with ADA. RESULTS: Six out of 23 (26%)
      patients developed AAA and had low ADA levels. Five out of six AAA-positive
      patients experienced LOR. In these patients use of concomitant methotrexate (MTX)
      was significantly lower. CONCLUSIONS: The occurrence of AAA is a frequent event
      associated with LOR. Monitoring of AAA and serum ADA levels should be considered
      in JIA patients under ADA therapy.

PMID- 25974289
TI  - 40 Years of the APOC Partnership.

PMID- 25974290
TI  - Synergistic role of dopants on the morphology of alloyed copper chalcogenide
      nanocrystals.
AB  - The presence of antimony, as a dopant in the colloidal growth reaction for CuIn(1
      x)Ga(x)S2 (CIGS) nanocrystals, causes end-to-end fusion of nanorod pairs into
      nanodumbbells at high yield. The influence of the dopant on shape is indirect;
      antimony catalyzes the incorporation of gallium, which is found in high
      concentration at the junction between the fused nanorods.

PMID- 25974291
TI  - The quest for balance.

PMID- 25974292
TI  - IgG "detoxes" the intestinal mucosa.
AB  - Secretory IgA is important in mucosal defense, but other, incompletely understood
      effectors exist. In this issue of Cell Host & Microbe, Kamada et al. (2015) show
      that IgG antibodies are produced against surface virulence factors of an
      intestinal attaching/effacing pathogen, bind to bacteria localized at the
      epithelium, and direct their destruction by mucosal and translocated neutrophils.

PMID- 25974293
TI  - Friend turned foe: a role for bacterial sulfatases in colitis.
AB  - During colitis, gut bacteria and bacterial components can traverse the mucus
      layer and contact host cells. In this issue of Cell Host & Microbe, Hickey et al.
      (2015) show that sulfatases of Bacteroides thetaiotaomicron are required for its
      outer membrane vesicles to transit to underlying host immune cells and cause
      colitis.

PMID- 25974294
TI  - Message in a biota: gut microbes signal to the circadian clock.
AB  - Circadian rhythm involves diurnal oscillations in biological processes. In this
      issue of Cell Host & Microbe, Leone et al. (2015) show that the gut microbiota
      influences the circadian clock and undergoes circadian oscillations. Microbiota
      produced metabolites change with host diet and may affect circadian rhythm,
      highlighting functional links between diet and physiology.

PMID- 25974295
TI  - Birth of the infant gut microbiome: moms deliver twice!
AB  - The infant gut is rapidly colonized by microbes shortly after birth. In this
      issue of Cell Host & Microbe,Backhed et al. (2015) shed new light on the assembly
      of the infant gut microbiome early in life, and how diet and delivery mode shape
      this community in a western human population.

PMID- 25974296
TI  - New Advances in the Effort against Ebola.
AB  - The unprecedented scale of the recent Ebola virus outbreak caused many to wonder
      whether this virus is different, and raised concerns about how to contain the
      outbreak. Two recent studies published in Science (Hoenen et al., 2015; Marzi et
      al., 2015) shed light on the subject and offer a new solution.

PMID- 25974297
TI  - Microbiota and autoimmunity: exploring new avenues.
AB  - Given the recognized role of the commensal microbiota in regulating host immunity
      to pathogens, it is not surprising that microbiota are also capable of regulating
      autoimmune responses. The underlying mechanisms of autoimmune regulation by the
      microbiota are just beginning to emerge. Here, we discuss possible pressure
      points toward the development of autoimmune diseases that can be influenced by
      the microbiota. Besides acting on the adaptive and innate arms of the immune
      response, the microbiota can affect the targets of autoimmunity directly, even
      during development in utero, and be involved in regulation of autoimmunity via
      interactions with hormones. 

PMID- 25974298
TI  - Antibiotics, pediatric dysbiosis, and disease.
AB  - Antibiotics are by far the most common medications prescribed for children.
      Recent epidemiological data suggests an association between early antibiotic use
      and disease phenotypes in adulthood. Antibiotic use during infancy induces
      imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to
      antibiotics and its potential link to disease development are especially complex
      to study in the changing infant gut. Here, we synthesize current knowledge
      linking antibiotics, dysbiosis, and disease and propose a framework for studying
      antibiotic-related dysbiosis in children. We recommend future studies into the
      microbiome-mediated effects of antibiotics focused on four types of dysbiosis:
      loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and
      blooms of pathogens. Establishment of a large and diverse baseline cohort to
      define healthy infant microbiome development is essential to advancing diagnosis,
      interpretation, and eventual treatment of pediatric dysbiosis. This approach will
      also help provide evidence-based recommendations for antibiotic usage in infancy.

PMID- 25974299
TI  - Control of brain development, function, and behavior by the microbiome.
AB  - Animals share an intimate and life-long partnership with a myriad of resident
      microbial species, collectively referred to as the microbiota. Symbiotic microbes
      have been shown to regulate nutrition and metabolism and are critical for the
      development and function of the immune system. More recently, studies have
      suggested that gut bacteria can impact neurological outcomes--altering behavior
      and potentially affecting the onset and/or severity of nervous system disorders.
      In this review, we highlight emerging evidence that the microbiome extends its
      influence to the brain via various pathways connecting the gut to the central
      nervous system. While understanding and appreciation of a gut microbial impact on
      neurological function is nascent, unraveling gut-microbiome-brain connections
      holds the promise of transforming the neurosciences and revealing potentially
      novel etiologies for psychiatric and neurodegenerative disorders.

PMID- 25974300
TI  - An integrative view of microbiome-host interactions in inflammatory bowel
      diseases.
AB  - The intestinal microbiota, which is composed of bacteria, viruses, and micro
      eukaryotes, acts as an accessory organ system with distinct functions along the
      intestinal tract that are critical for health. This review focuses on how the
      microbiota drives intestinal disease through alterations in microbial community
      architecture, disruption of the mucosal barrier, modulation of innate and
      adaptive immunity, and dysfunction of the enteric nervous system. Inflammatory
      bowel disease is used as a model system to understand these microbial-driven
      pathologies, but the knowledge gained in this space is extended to less-well
      studied intestinal diseases that may also have an important microbial component,
      including environmental enteropathy and chronic colitis-associated colorectal
      cancer. 

PMID- 25974302
TI  - Microbiota and Host Nutrition across Plant and Animal Kingdoms.
AB  - Plants and animals each have evolved specialized organs dedicated to nutrient
      acquisition, and these harbor specific bacterial communities that extend the
      host's metabolic repertoire. Similar forces driving microbial community
      establishment in the gut and plant roots include diet/soil-type, host genotype,
      and immune system as well as microbe-microbe interactions. Here we show that
      there is no overlap of abundant bacterial taxa between the microbiotas of the
      mammalian gut and plant roots, whereas taxa overlap does exist between fish gut
      and plant root communities. A comparison of root and gut microbiota composition
      in multiple host species belonging to the same evolutionary lineage reveals host
      phylogenetic signals in both eukaryotic kingdoms. The reasons underlying striking
      differences in microbiota composition in independently evolved, yet functionally
      related, organs in plants and animals remain unclear but might include
      differences in start inoculum and niche-specific factors such as oxygen levels,
      temperature, pH, and organic carbon availability. 

PMID- 25974301
TI  - Microbiota in allergy and asthma and the emerging relationship with the gut
      microbiome.
AB  - Asthma and atopy, classically associated with hyper-activation of the T helper 2
      (Th2) arm of adaptive immunity, are among the most common chronic illnesses
      worldwide. Emerging evidence relates atopy and asthma to the composition and
      function of the human microbiome, the collection of microbes that reside in and
      on and interact with the human body. The ability to interrogate microbial ecology
      of the human host is due in large part to recent technological developments that
      permit identification of microbes and their products using culture-independent
      molecular detection techniques. In this review we explore the roles of
      respiratory, gut, and environmental microbiomes in asthma and allergic disease
      development, manifestation, and attenuation. Though still a relatively nascent
      field of research, evidence to date suggests that the airway and/or gut
      microbiome may represent fertile targets for prevention or management of allergic
      asthma and other diseases in which adaptive immune dysfunction is a prominent
      feature. 

PMID- 25974303
TI  - The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of
      Small Molecules between the Host and the Parasitophorous Vacuole.
AB  - Toxoplasma gondii is a protozoan pathogen in the phylum Apicomplexa that resides
      within an intracellular parasitophorous vacuole (PV) that is selectively
      permeable to small molecules through unidentified mechanisms. We have identified
      GRA17 as a Toxoplasma-secreted protein that localizes to the parasitophorous
      vacuole membrane (PVM) and mediates passive transport of small molecules across
      the PVM. GRA17 is related to the putative Plasmodium translocon protein EXP2 and
      conserved across PV-residing Apicomplexa. The PVs of GRA17-deficient parasites
      have aberrant morphology, reduced permeability to small molecules, and structural
      instability. GRA17-deficient parasites proliferate slowly and are avirulent in
      mice. These GRA17-deficient phenotypes are rescued by complementation with
      Plasmodium EXP2. GRA17 functions synergistically with a related protein, GRA23.
      Exogenous expression of GRA17 or GRA23 alters the membrane conductance properties
      of Xenopus oocytes in a manner consistent with a large non-selective pore. Thus,
      GRA17 and GRA23 provide a molecular basis for PVM permeability and nutrient
      access. 

PMID- 25974304
TI  - Blockade of interferon Beta, but not interferon alpha, signaling controls
      persistent viral infection.
AB  - Although type I interferon (IFN-I) is thought to be beneficial against microbial
      infections, persistent viral infections are characterized by high interferon
      signatures suggesting that IFN-I signaling may promote disease pathogenesis.
      During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNalpha
      and IFNbeta are highly induced early after infection, and blocking IFN-I receptor
      (IFNAR) signaling promotes virus clearance. We assessed the specific roles of
      IFNbeta versus IFNalpha in controlling LCMV infection. While blockade of IFNbeta
      alone does not alter early viral dissemination, it is important in determining
      lymphoid structure, lymphocyte migration, and anti-viral T cell responses that
      lead to accelerated virus clearance, approximating what occurs during attenuation
      of IFNAR signaling. Comparatively, blockade of IFNalpha was not associated with
      improved viral control, but with early dissemination of virus. Thus, despite
      their use of the same receptor, IFNbeta and IFNalpha have unique and
      distinguishable biologic functions, with IFNbeta being mainly responsible for
      promoting viral persistence.

PMID- 25974305
TI  - Colitogenic Bacteroides thetaiotaomicron Antigens Access Host Immune Cells in a
      Sulfatase-Dependent Manner via Outer Membrane Vesicles.
AB  - Microbes interact with the host immune system via several potential mechanisms.
      One essential step for each mechanism is the method by which intestinal microbes
      or their antigens access specific host immune cells. Using genetically
      susceptible mice (dnKO) that develop spontaneous, fulminant colitis, triggered by
      Bacteroides thetaiotaomicron (B. theta), we investigated the mechanism of
      intestinal microbial access under conditions that stimulate colonic inflammation.
      B. theta antigens localized to host immune cells through outer membrane vesicles
      (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic
      sulfatase maturating enzyme (anSME) from B. theta, which is required for post
      translational activation of all B. theta sulfatase enzymes. This bacterial mutant
      strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to
      host immune cells was sulfatase dependent. These data demonstrate that bacterial
      OMVs and associated enzymes promote inflammatory immune stimulation in
      genetically susceptible hosts.

PMID- 25974306
TI  - Dynamics and Stabilization of the Human Gut Microbiome during the First Year of
      Life.
AB  - The gut microbiota is central to human health, but its establishment in early
      life has not been quantitatively and functionally examined. Applying metagenomic
      analysis on fecal samples from a large cohort of Swedish infants and their
      mothers, we characterized the gut microbiome during the first year of life and
      assessed the impact of mode of delivery and feeding on its establishment. In
      contrast to vaginally delivered infants, the gut microbiota of infants delivered
      by C-section showed significantly less resemblance to their mothers. Nutrition
      had a major impact on early microbiota composition and function, with cessation
      of breast-feeding, rather than introduction of solid food, being required for
      maturation into an adult-like microbiota. Microbiota composition and ecological
      network had distinctive features at each sampled stage, in accordance with
      functional maturation of the microbiome. Our findings establish a framework for
      understanding the interplay between the gut microbiome and the human body in
      early life. 

PMID- 25974308
TI  - Improved efficacy of soluble human receptor activator of nuclear factor kappa B
      (RANK) fusion protein by site-directed mutagenesis.
AB  - Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin
      (hRANK-Ig) has been considered as one of the therapeutic agents to treat
      osteoporosis or diseases associated with bone destruction by blocking the
      interaction between RANK and the receptor activator of nuclear factor kappa B
      ligand (RANKL). However, no scientific record showing critical amino acid
      residues within the structural interface between the human RANKL and RANK complex
      is yet available. In this study, we produced several mutants of hRANK-Ig by
      replacement of amino acid residue(s) and tested whether the mutants had increased
      binding affinity to human RANKL. Based on the results from flow cytometry and
      surface plasmon resonance analyses, the replacement of E(125) with D(125), or
      E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3
      of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK
      Ig. This result may provide the first example of improvement in the efficacy of
      hRANK-Ig by protein engineering and may give additional information to understand
      a more defined structural interface between hRANK and RANKL. 

PMID- 25974309
TI  - Ultra-broadband and strongly enhanced diffraction with metasurfaces.
AB  - Enhanced high-order diffractions which are spatially dispersive are desirable in
      such as spectroscopy studies, thin-film solar cells, etc. Conventionally, the
      dielectric gratings can be used to realize the enhanced diffraction, but the
      facets are usually rugged and optically thick (~MUm). Plasmonic materials may
      exhibit unprecedented ability for manipulating light. Nonetheless, much interest
      has been focused on the subwavelength metasurfaces working in the zero-order
      regime. Here, we show that ultra-broadband and strongly enhanced diffraction can
      be achieved with the super-wavelength metasurfaces. For the purpose, we employ
      symmetric or asymmetric metal patches on a ground metal plane, which support the
      localized oscillation of free electrons and enhanced scattering of light. The
      zero-order reflection is suppressed, giving rise to an enhancement of first-order
      diffraction (50 ~ 95%) in an ultra-wide bandwidth (600 ~ 1500 nm). The proposed
      plasmonic structure is planar and ultra-thin (with an etching depth of only 80
      nm), showing new potential for constructing compact and efficient dispersive
      elements. 

PMID- 25974307
TI  - Marine lipopeptide Iturin A inhibits Akt mediated GSK3beta and FoxO3a signaling
      and triggers apoptosis in breast cancer.
AB  - Akt kinase is a critical component of the PI3K/Akt signaling pathway, which is
      frequently over expressed in human cancers including breast. Therapeutic regimens
      for inhibiting breast cancer with aberrant Akt activity are essential. Here, we
      evaluated antitumor effect of a marine bacteria derived lipopeptide 'Iturin A' on
      human breast cancer in vitro and in vivo through disrupting Akt pathway.
      Proliferation of MDA-MB-231 and MCF-7 breast cancer cells were significantly
      inhibited by Iturin A and it induced apoptosis as confirmed by increased Sub G1
      populations, DNA fragmentation, morphological changes and western blot analysis.
      Furthermore, Iturin A inhibited EGF induced Akt phosphorylation (Ser473 and
      Thr308) and its downstream targets GSK3beta and FoxO3a. Iturin A inactivated MAPK
      as well as Akt kinase leading to the translocation of FoxO3a to the nucleus. Gene
      silencing of Akt in MDA-MB-231 and MCF-7 cells reduced the sensitivity of cancer
      cells to Iturin A. Interestingly, overexpression of Akt with Akt plasmid in
      cancer cells caused highly susceptible to induce apoptosis by Iturin A treatment.
      In a xenograft model, Iturin A inhibited tumor growth with reduced expressions of
      Ki-67, CD-31, P-Akt, P-GSK3beta, P-FoxO3a and P-MAPK. Collectively, these
      findings imply that Iturin A has potential anticancer effect on breast cancer. 

PMID- 25974310
TI  - Distribution of the Multidrug Resistance Gene cfr in Staphylococcus Isolates from
      Pigs, Workers, and the Environment of a Hog Market and a Slaughterhouse in
      Guangzhou, China.
AB  - Bacteria harboring cfr, a multidrug resistance gene, have high prevalence in
      livestock in China and might be transmitted to humans through direct contact or
      via contaminated food products. To better understand the epidemiology of cfr
      producers in the food chain, the prevalence and genetic analysis of
      Staphylococcus isolates recovered from pigs, workers, and meat-handling
      facilities (a slaughterhouse and a hog market in Guangzhou, China) were examined.
      Twenty (4.5%) cfr-positive Staphylococcus isolates (18 Staphylococcus simulans, 1
      S. cohnii, and 1 S. aureus) were derived from pigs (16/312), the environment
      (2/52), and workers (2/80). SmaI pulsed-field gel electrophoresis of 26
      staphylococcal strains (22 S. simulans and 4 S. cohnii), including previously
      reported cfr-carrying staphylococci of animal food origin, exhibited 19 major
      pulsed-field gel electrophoresis patterns (A-S). Clonal spread of cfr-carrying
      staphylococci among pigs, workers, and meat products was detected. The genetic
      contexts of cfr in plasmids (pHNKF3, pHNZT2, and pHNCR35) obtained from S.
      simulans of swine or human origin were similar to that of Staphylococcus species
      isolated from human clinics and animal-derived food. The cfr-carrying S. aureus
      strain isolated from floor swabs of the hog market was spa-type t889 and belonged
      to the ST9 clonal lineage. In summary, both clonal spread and horizontal
      transmission via mobile elements contributed to cfr dissemination among
      staphylococcal isolates obtained from different sources. To monitor potential
      outbreaks of cfr-positive bacteria, continued surveillance of this gene in
      animals at slaughter and in animal-derived food is warranted. 

PMID- 25974312
TI  - The epigenetic regulation of the opioid system: new individualized prompt
      prevention and treatment strategies.
AB  - The most well-known physiological effect associated with opiod system is their
      efficacy in pain reduction or analgesia, although their effect on a variety of
      other physiological and physiophological functions has become apparent in recent
      years. This review is an attempt to clarify in more detail the epigenetic
      regulation of opioid system to understand with more precision their
      transcriptional and posttranscriptional regulation in multiple pyisiological and
      pharmacological contexts. The opioid receptors show an epigenetic regulation and
      opioid peptide precursors by methylation, chromatin remodeling and microRNA.
      Although the opioid receptor promoters have similarity between them, they use
      different epigenetic regulation forms and they exhibit different pattern of
      expression during the cell differentiation. DNA methylation is also confirmed in
      opioid peptide precursors, being important for gene expression and tissue
      specificity. Understanding the epigenetic basis of those physiological and
      physiopathological procesess is essential for the development of individualized
      prompt prevention and treatment strategies.

PMID- 25974311
TI  - Restoration of riparian vegetation: A global review of implementation and
      evaluation approaches in the international, peer-reviewed literature.
AB  - We examined how restoration of riparian vegetation has been implemented and
      evaluated in the scientific literature during the past 25 years. A total of 169
      papers were read systematically to extract information about the following: 1)
      restoration strategies applied, 2) scale of monitoring and use of reference
      sites, 3) metrics used for evaluation, and 4) drivers of success. Hydro
      geomorphic approaches (e.g., dam operations, controlled floods, landform
      reconfiguration) were the most frequent, followed by active plant introduction,
      exotic species control, natural floodplain conversion and grazing and herbivory
      control. Our review revealed noteworthy limitations in the spatio-temporal
      approaches chosen for evaluation. Evaluations were mostly from one single project
      and frequently ignored the multi-dimensional nature of rivers: landscape spatial
      patterns were rarely assessed, and most projects were assessed locally (i.e.,
      <=meander scale). Monitoring rarely lasted for more than six years and the
      projects evaluated were usually not more than six years old. The impact of the
      restoration was most often (43%) assessed by tracking change over time rather
      than by comparing restored sites to unrestored and reference sites (12%), and few
      projects (30%) did both. Among the ways which restoration success was evaluated,
      vegetation structure (e.g., abundance, density, etc.) was assessed more often
      (152 papers) than vegetation processes (e.g., biomass accumulation, survival,
      etc.) (112 papers) and vegetation diversity (78 papers). Success was attributed
      to hydro-geomorphic factors in 63% of the projects. Future evaluations would
      benefit from incorporating emerging concepts in ecology such as functional traits
      to assess recovery of functionality, more rigorous experimental designs, enhanced
      comparisons among projects, longer term monitoring and reporting failure. 

PMID- 25974313
TI  - Singlet ground state actinide chemistry with geminals.
AB  - We present the first application of the variationally orbital optimized
      antisymmetric product of 1-reference orbital geminals (vOO-AP1roG) method to
      singlet-state actinide chemistry. We assess the accuracy and reliability of the
      AP1roG ansatz in modelling the ground-state electronic structure of small
      actinide compounds by comparing it to standard quantum chemistry approaches. Our
      study of the ground state spectroscopic constants (bond lengths and vibrational
      frequencies) and potential energy curves of actinide oxides (UO2(2+) and ThO2) as
      well as the energetic stability of ThC2 isomers reveals that vOO-AP1roG describes
      the electronic structure of heavy-element compounds accurately, at mean-field
      computational cost. 

PMID- 25974314
TI  - Neurogenetics and gene therapy for reward deficiency syndrome: are we going to
      the Promised Land?
AB  - INTRODUCTION: Addiction is a substantial health issue with limited treatment
      options approved by the FDA and as such currently available. The advent of
      neuroimaging techniques that link neurochemical and neurogenetic mechanisms to
      the reward circuitry brain function provides a framework for potential genomic
      based therapies. AREAS COVERED: Through candidate and genome-wide association
      studies approaches, many gene polymorphisms and clusters have been implicated in
      drug, food and behavioral dependence linked by the common rubric reward
      deficiency syndrome (RDS). The results of selective studies that include the role
      of epigenetics, noncoding micro RNAs in RDS behaviors especially drug abuse
      involving alcohol, opioids, cocaine, nicotine, pain and feeding are reviewed in
      this article. New targets for addiction treatment and relapse prevention,
      treatment alternatives such as gene therapy in animal models, and
      pharmacogenomics and nutrigenomics methods to manipulate transcription and gene
      expression are explored. EXPERT OPINION: The recognition of the clinical benefit
      of early genetic testing to determine addiction risk stratification and
      dopaminergic agonistic, rather than antagonistic therapies are potentially the
      genomic-based wave of the future. In addition, further development, especially in
      gene transfer work and viral vector identification, could make gene therapy for
      RDS a possibility in the future.

PMID- 25974315
TI  - Comparison of feeding behavior between two different-sized groups of Japanese
      macaques (Macaca fuscata yakui).
AB  - Group-living animals face intragroup scramble and intergroup contest
      competitions. Many studies have shown that larger groups bear the costs of
      intragroup scramble competition, which negatively affects the reproductive
      success of females. Unlike most primate species, Japanese macaques in the
      Yakushima coastal forest show increased reproductive success with group size.
      However, it remains unclear how group size affects the behavior of macaques. The
      present study examined the effects of group size on the feeding behavior of
      Japanese macaques in the Yakushima coastal forest. We investigated 9-13 adult
      females from two different-sized groups via focal animal sampling during October
      2012-August 2013. We compared the feeding behavior, including patch use, between
      the two groups. The larger group had a larger home range and spent more time
      feeding, especially on mature leaves. This suggests that intragroup feeding
      competition should be more intense in the larger group than in the smaller group.
      The feeding of mature leaves might enable the larger group to increase the number
      of co-feeding individuals. Contrary to the predictions that the larger group
      travels longer distances and spends more time moving, the smaller group traveled
      longer distances, and spent more time moving, although the number of visited
      patches did not differ between the two groups. The immediate consequences of the
      loss of inter-group encounters could accumulate as daily travel costs,
      considering that group size is associated with inter-group dominance and that
      intergroup aggressive encounters occur frequently in the Yakushima coastal
      forest. This suggests that the smaller group has increased travel costs as a
      result of intergroup contest competition, which leads to decline in reproductive
      success. Am. J. Primatol. 77:986-1000, 2015. (c) 2015 Wiley Periodicals, Inc.

PMID- 25974316
TI  - One Year Incidence of Atrial Septal Defect after PV Isolation: A Comparison
      Between Conventional Radiofrequency and Cryoballoon Ablation.
AB  - BACKGROUND: Transseptal (TS) catheterization is needed to access the left heart
      during pulmonary vein isolation (PVI) procedures. In the radiofrequency (RF)
      ablation procedure, left atrial access is commonly achieved with a double TS
      puncture; cryoballoon (CB) ablation usually requires only a single TS puncture.
      Our aim was to compare the incidence of iatrogenic septal defect (IASD) between
      double transseptal conventional RF and CB ablation. METHODS AND RESULTS:
      Individuals having undergone PVI as index procedure by RF or CB ablation and a
      subsequent transesophageal echocardiography examination during postablation
      follow-up in our center were consecutively included. A total of 127 patients
      formed the study group (92 males; mean age 60 +/- 11 years). IASD was present in
      17 patients (13.4%) after a mean follow-up time of 11.6 months. The incidence of
      IASD at 1-year follow-up following PVI was significantly higher in the CB
      ablation group compared with the RF ablation group (22.2% vs 8.5%; P = 0.03).
      Mean IASD diameter was larger in the CB group (0.60 cm * 0.50 cm vs 0.44 cm *
      0.35 cm) without statistical significance. Only left to right atrial shunt was
      observed. No adverse events were recorded in these patients during the follow-up.
      CONCLUSIONS: the incidence of IASD at 1-year follow-up following CB ablation
      procedure for PVI is significantly higher with respect to RF procedures. Although
      no adverse clinical events were recorded in patients with persistence of IASD,
      more detailed echocardiographic examinations might be advised in all individuals
      exhibiting this finding.

PMID- 25974318
TI  - Copy number variants including RAS pathway genes-How much RASopathy is in the
      phenotype?
AB  - The RASopathies comprise a group of clinically overlapping developmental
      syndromes the common pathogenetic basis of which is dysregulated signal flow
      through the RAS-MAPK pathway. Mutations in several components or modifiers of the
      pathway have been identified in Noonan syndrome and related disorders. Over the
      past years copy number variants (CNVs) encompassing RAS pathway genes (PTPN11,
      RAF1, MEK2, or SHOC2) have been reported in children with developmental
      syndromes. These observations raised speculations that the associated phenotypes
      represent RASopathies, implying that the increased or reduced expression of the
      respective RAS pathway component and a consecutive dysregulation of RAS pathway
      signalling is responsible for the clinical picture. Herein, we present two
      individuals and three of their relatives harboring duplications of either 3p25.2
      including the RAF1 locus or 19p13.3 including the MEK2 locus. Duplication
      carriers exhibited variable clinical phenotypes including non-specific facial
      dysmorphism, short stature, and learning difficulties. A careful review of the
      literature supported the impression that phenotypes associated with CNVs
      including RAS pathway genes commonly share non-specific symptoms with
      RASopathies, while the characteristic "gestalt" is lacking. Considering the known
      molecular pathogenesis of RASopathies, it is questionable that a modest increase
      in the expression of a functionally normal signaling component can mimic the
      effects of a qualitatively abnormal (hyperactive) mutant protein. We thus argue
      that current empirical and biological evidence is still insufficient to allow the
      conclusion that an altered copy number of a RAS pathway component is indeed the
      mechanism that is critical for the phenotype associated with CNVs including
      RASopathy genes.

PMID- 25974317
TI  - Evolutionarily conserved network properties of intrinsically disordered proteins.
AB  - BACKGROUND: Intrinsically disordered proteins (IDPs) lack a stable tertiary
      structure in isolation. Remarkably, however, a substantial portion of IDPs
      undergo disorder-to-order transitions upon binding to their cognate partners.
      Structural flexibility and binding plasticity enable IDPs to interact with a
      broad range of partners. However, the broader network properties that could
      provide additional insights into the functional role of IDPs are not known.
      RESULTS: Here, we report the first comprehensive survey of network properties of
      IDP-induced sub-networks in multiple species from yeast to human. Our results
      show that IDPs exhibit greater-than-expected modularity and are connected to the
      rest of the protein interaction network (PIN) via proteins that exhibit the
      highest betweenness centrality and connect to fewer-than-expected IDP
      communities, suggesting that they form critical communication links from IDP
      modules to the rest of the PIN. Moreover, we found that IDPs are enriched at the
      top level of regulatory hierarchy. CONCLUSION: Overall, our analyses reveal
      coherent and remarkably conserved IDP-centric network properties, namely,
      modularity in IDP-induced network and a layer of critical nodes connecting IDPs
      with the rest of the PIN.

PMID- 25974320
TI  - Editorial Comment to Progression of hypertension after partial nephrectomy in
      patients with renal tumors: A preliminary report.

PMID- 25974319
TI  - Microenvironmental control of stem cell fate in intestinal homeostasis and
      disease.
AB  - The conventional model of intestinal epithelial architecture describes a
      unidirectional tissue organizational hierarchy with stem cells situated at the
      crypt base and daughter cells proliferating and terminally differentiating as
      they progress along the vertical (crypt-luminal) axis. In this model, the fate of
      a cell that has left the niche is determined and its lifespan limited. Evidence
      is accumulating to suggest that stem cell control and daughter cell fate
      determination is not solely an intrinsic, cell autonomous property but is heavily
      influenced by the microenvironment including paracrine, mesenchymal, and
      endogenous epithelial morphogen gradients. Recent research suggests that in
      intestinal homeostasis, stem cells transit reversibly between states of variable
      competence in the niche. Furthermore, selective pressures that disrupt the
      homeostatic balance, such as intestinal inflammation or morphogen dysregulation,
      can cause committed progenitor cells and even some differentiated cells to regain
      stem cell properties. Importantly, it has been recently shown that this
      disruption of cell fate determination can lead to somatic mutation and neoplastic
      transformation of cells situated outside the crypt base stem cell niche. This
      paper reviews the exciting developments in the study of stem cell dynamics in
      homeostasis, intestinal regeneration, and carcinogenesis, and explores the
      implications for human disease and cancer therapies.

PMID- 25974321
TI  - Changes in vaginal physiology of menopausal women with type 2 diabetes.
AB  - INTRODUCTION: Metabolic disorders, such as type 2 diabetes, have been associated
      with an increased risk of development of female sexual dysfunction (FSD). In
      experimental studies, vascular, neuronal, and hormonal responsiveness alteration
      at vaginal level were proposed as contributors to the onset of FSD in women with
      diabetes; however, conclusive data on humans are still lacking. AIMS: The study
      aimed to assess changes in vascularization, sex steroid receptors, nitric oxide
      synthase, and aquaporin-2 (AQP2) expression occurring at vaginal level in women
      with diabetes. METHODS: Vaginal biopsies were obtained from 21 postmenopausal
      women, 10 of whom were diagnosed as having type 2 diabetes mellitus. CD31,
      estrogen receptor-alpha (ERalpha) and androgen receptor (AR) expression and
      localization were analyzed by immunostaining. Expression of endothelial (eNOS)
      and neuronal (nNOS) nitric oxide synthase isoforms and AQP2 were also assessed in
      vaginal samples. MAIN OUTCOMES MEASURES: Changes in vaginal vascularization, sex
      steroids receptor, eNOS, nNOS and AQP2 expression. RESULTS: Vaginal samples from
      women with diabetes showed an increased microvessel density in the lamina
      propria, which were morphologically disrupted suggesting an angiogenic
      compensatory mechanism. While no differences were seen in ERalpha, AR expression
      was significantly reduced in the vaginal epithelium and lamina propria of women
      with diabetes. Similarly, the gene and protein expressions of both nNOS and eNOS
      were significantly reduced in patients with diabetes, while AQP2 mRNAs level did
      not significantly differ between the two groups. CONCLUSION: Diabetes greatly
      impacts vaginal physiology, being associated with alterations of the vaginal
      lamina propria vascular network, nitrergic signaling, and AR expression. These
      alterations may contribute to the increased risk of FSD development in women with
      diabetes.

PMID- 25974322
TI  - Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal
      cortex and hippocampal emotional processing in panic and major depressive
      disorder.
AB  - OBJECTIVE: The aim of the study was to evaluate the association of transmembrane
      protein 132D (TMEM132D), catechol-O-methyltransferase (COMT), and gamma
      aminobutyric acid (GABA) receptor alpha 6 subunit (GABRA6) genotypes with
      cingulate, frontal cortex and hippocampal emotional processing in panic disorder
      (PD) and major depressive disorder (MDD). METHOD: The single nucleotide
      polymorphisms (SNPs) in TMEM132D, COMT, and GABRA6 were examined in patients with
      MDD, PD, and healthy controls. Functional magnetic resonance imaging (fMRI) was
      performed in patients with MDD, PD, and healthy controls. RESULTS: rs4680 in COMT
      and rs3219151 in GABRA6 showed positive associations with PD and MDD. A dynamic
      fearful face was shown to the participants during fMRI scanning. In PD patients,
      responses in the bilateral anterior cingulate were stronger in carriers of the AA
      genotype of SNP rs11060369 in TMEM132D compared with carriers of the AC + CC
      genotype, and stronger in CT + TT genotype carriers of SNP rs3219151 in GABRA6
      compared with carriers of the CC genotype. The response in the medial orbital
      frontal cortex was stronger in carriers of the CT + TT genotypes of SNP rs3219151
      in PD. In MDD patients, the response in the right parahippocampus of carriers of
      the GG genotype of rs4680 in COMT was stronger than that of carriers of the AA +
      AG genotype. CONCLUSION: These results suggest that TMEM132D, GABRA6, and COMT
      variants may increase vulnerability to panic.

PMID- 25974323
TI  - Self-perception of competencies in adolescents with autism spectrum disorders.
AB  - Research has demonstrated that, despite difficulties in multiple domains,
      children with autism spectrum disorders (ASD) show a lack of awareness of these
      difficulties. A misunderstanding of poor competencies may make it difficult for
      individuals to adjust their behaviour in accordance with feedback and may lead to
      greater impairments over time. This study examined self-perceptions of
      adolescents with ASD (n = 19) and typically developing (TD) mental-age-matched
      controls (n = 22) using actual performance on objective academic tasks as the
      basis for ratings. Before completing the tasks, participants were asked how well
      they thought they would do (pre-task prediction). After completing each task,
      they were asked how well they thought they did (immediate post-performance) and
      how well they would do in the future (hypothetical future post-performance).
      Adolescents with ASD had more positively biased self-perceptions of competence
      than TD controls. The ASD group tended to overestimate their performance on all
      ratings of self-perceptions (pre-task prediction, immediate, and hypothetical
      future post-performance). In contrast, while the TD group was quite accurate at
      estimating their performance immediately before and after performing the task,
      they showed some tendency to overestimate their future performance. Future
      investigation is needed to systematically examine possible mechanisms that may be
      contributing to these biased self-perceptions.

PMID- 25974324
TI  - Short Communication: Contribution of Voltage-Gated Sodium Channels to the Rabbit
      Cone Electroretinograms.
AB  - PURPOSE: Although the rabbit eye is of a similar size to the human eye, our
      limited understanding of the differences in retinal physiology to other species
      hinders its use in retinal research. The role of voltage-gated sodium channels
      (Nav) in the propagation of excitatory potentials along bipolar cells remains
      unclear, as conflicting data have been reported in the rabbit. The present study
      assesses the relative contributions of Nav to the scotopic and photopic flash
      ERGs as well as the wavelength-dependence of Nav blockade on the rabbit flicker
      ERG. MATERIALS AND METHODS: Tetrodotoxin (TTX, 1 MUM) was injected into the
      vitreous cavity of Chinchilla bastard rabbits. Scotopic ERGs were evoked by white
      flashes ranging from 10(-5) to 10 cds m(-2), photopic ERGs on a background of 25
      cdm(-2) using flash intensities of 0.032-25 cds m(-2). Flicker ERGs (3-50 Hz)
      were elicited by blue, green and yellow stimuli at 2.34 cds m(-2) on a white
      background of 30 cdm(-2). RESULTS: The a- and b-waves of the scotopic ERG were
      unaffected by intravitreal injection of the Nav blocker TTX. In contrast, the b
      wave, but not the a-wave, of the photopic ERG was selectively blocked by TTX. The
      reduction by TTX of the flicker ERG was greater for blue than for green and
      yellow stimuli. DISCUSSION: The data suggest that Nav selectively contribute to
      the generation of the photopic b-wave in the rabbit, indicating that they play an
      important role in the propagation of excitatory signals on bipolar cells in the
      cone, but not rod pathways. Importantly, the present study resolves conflicting
      previous reports into the role of Nav in the retinal function of the rabbit.

PMID- 25974325
TI  - Laparoscopic Orchiopexy Requiring Vascular Division: A Randomized Study Comparing
      the Primary and Two-Stage Approaches.
AB  - BACKGROUND: Intraabdominal testes that lack sufficient vessel length to perform
      an orchiopexy require division of the testicular vessels. Historically, the
      vessels are divided at the initial operation, and the orchiopexy is then
      performed as a two-stage procedure with the assumption for the development of
      neovascularization along the vas deferens during the interim. Recent reports
      suggest the orchiopexy may be performed primarily at the time of vessel division.
      However, these strategies have not been prospectively compared. Therefore, we
      conducted a randomized pilot trial to examine the role for a larger comparative
      study. PATIENTS AND METHODS: After Internal Review Board approval, all patients
      undergoing laparoscopic orchiopexy for a nonpalpable testis were considered for
      enrollment. This study was designed as a pilot study to evaluate testicular
      survival at 6 months of follow-up. After consent was obtained, computer
      randomization was used to determine a primary or two-stage orchiopexy. All
      procedures were performed by five surgeons, and allotment had no affect on
      surgeon selection. RESULTS: Between October 2007 and September 2013, 112 patients
      were enrolled in the study. Twenty-seven patients (14 primary and 13 two-stage)
      met criteria for randomization based on inability to bring the testis to the
      contralateral internal ring. There was no difference in the approach among
      surgeons. Mean operative time and cost significantly favored the primary
      approach, and testicular survival rates were the same. CONCLUSIONS: Based on the
      data in our pilot study, approximately 70% of patients with a nonpalpable testis
      will not require vascular division. This study suggests that when vascular
      division is required, the primary orchiopexy may be equivalent to the traditional
      two-stage procedure with regard to testicular survival and superior to the two
      stage in total operative time and charges. These data provide evidence for
      sufficient equipoise to proceed with the development of a large multi
      institutional trial comparing these two approaches.

PMID- 25974326
TI  - Multi-organ localization with cascaded global-to-local regression and shape
      prior.
AB  - We propose a method for fast, accurate and robust localization of several organs
      in medical images. We generalize the global-to-local cascade of regression random
      forest to multiple organs. A first regressor encodes the global relationships
      between organs, learning simultaneously all organs parameters. Then subsequent
      regressors refine the localization of each organ locally and independently for
      improved accuracy. By combining the regression vote distribution and the organ
      shape prior (through probabilistic atlas representation) we compute confidence
      maps that are organ-dedicated probability maps. They are used within the cascade
      itself, to better select the test voxels for the second set of regressors, and to
      provide richer information than the classical bounding boxes result thanks to the
      shape prior. We propose an extensive study of the different learning and testing
      parameters, showing both their robustness to reasonable perturbations and their
      influence on the final algorithm accuracy. Finally we demonstrate the robustness
      and accuracy of our approach by evaluating the localization of six abdominal
      organs (liver, two kidneys, spleen, gallbladder and stomach) on a large and
      diverse database of 130 CT volumes. Moreover, the comparison of our results with
      two existing methods shows significant improvements brought by our approach and
      our deep understanding and optimization of the parameters. 

PMID- 25974327
TI  - Development and Integration of Genome-Wide Polymorphic Microsatellite Markers
      onto a Reference Linkage Map for Constructing a High-Density Genetic Map of
      Chickpea.
AB  - The identification of informative in silico polymorphic genomic and genic
      microsatellite markers by comparing the genome and transcriptome sequences of
      crop genotypes is a rapid, cost-effective and non-laborious approach for large
      scale marker validation and genotyping applications, including construction of
      high-density genetic maps. We designed 1494 markers, including 1016 genomic and
      478 transcript-derived microsatellite markers showing in-silico fragment length
      polymorphism between two parental genotypes (Cicer arietinum ICC4958 and C.
      reticulatum PI489777) of an inter-specific reference mapping population. High
      amplification efficiency (87%), experimental validation success rate (81%) and
      polymorphic potential (55%) of these microsatellite markers suggest their
      effective use in various applications of chickpea genetics and breeding. Intra
      specific polymorphic potential (48%) detected by microsatellite markers in 22
      desi and kabuli chickpea genotypes was lower than inter-specific polymorphic
      potential (59%). An advanced, high-density, integrated and inter-specific
      chickpea genetic map (ICC4958 x PI489777) having 1697 map positions spanning
      1061.16 cM with an average inter-marker distance of 0.625 cM was constructed by
      assigning 634 novel informative transcript-derived and genomic microsatellite
      markers on eight linkage groups (LGs) of our prior documented, 1063 marker-based
      genetic map. The constructed genome map identified 88, including four major (7-23
      cM) longest high-resolution genomic regions on LGs 3, 5 and 8, where the maximum
      number of novel genomic and genic microsatellite markers were specifically
      clustered within 1 cM genetic distance. It was for the first time in chickpea
      that in silico FLP analysis at genome-wide level was carried out and such a large
      number of microsatellite markers were identified, experimentally validated and
      further used in genetic mapping. To best of our knowledge, in the presently
      constructed genetic map, we mapped highest number of new sequence-based robust
      microsatellite markers (634) which is an advancement over the previously
      documented (~300 markers) inter-specific genetic maps. This advanced high-density
      map will serve as a foundation for large-scale marker validation and genotyping
      applications, including identification and targeted mapping of trait-specific
      genes/QTLs (quantitative trait loci) with sub-optimal use of resources and labour
      in chickpea. 

PMID- 25974328
TI  - Culturally Competent Strategies for Recruitment and Retention of African American
      Populations into Clinical Trials.
AB  - PURPOSE: To identify successful recruitment strategies, challenges and best
      practices for researchers to engage African American communities in clinical
      studies taken into consideration target participants' culture and context.
      METHODS: We reviewed 50 studies conducted from 2001 to 2012 at an inner-city
      research center to determine the type, duration, anticipated enrollments and
      actual enrollments. Survey was sent to study coordinators to obtain data on
      recruitment and retention strategies, challenges and dropout rates. We also
      interviewed 25 study coordinators on challenges and strategies. RESULTS: Of the
      50 studies, 24 had completed recruitment at the time of this report. The
      completed studies achieved a median recruitment rate of 88% (range: 50-110).
      Successful recruitment and retention strategies included: field-based strategy
      and snowballing. Major barriers were: distrust, compensation, education
      disadvantage, lack of interest, and inability to have study partner. Strategies
      to reduce barriers included providing informational sessions, disseminating
      newsletters about study outcomes. Best practices include being culturally
      sensitive including demonstrating a caring attitude and being responsive to
      participants needs. CONCLUSIONS: Cultural competence is critical in order to
      design and implement successful recruitment strategies in this population.
      Research teams should consist of multiethnic staff, involve the community,
      demonstrate trust and deliver concise education of the research endeavor.

PMID- 25974330
TI  - Relationship between pharyngitis and peri-odontoid pannus: A new etiology for
      some Chiari I malformations?
AB  - The pathophysiology underlying Chiari I malformations (CIMs) provides room for
      debate with several theories attempting to address this issue. We retrospectively
      reviewed many of our past patients with pediatric CIMs (specifically, those with
      peri-odontoid pannus), and present a hypothesis for the development of the
      malformation in some of said patients. Our experience with the pediatric CIM has
      shown that almost 1 in 20 patients who present with symptoms is found to have a
      peri-odontoid pannus. These masses ranged in size from 4 to 11 mm in diameter.
      Forty percent had a history of clinically significant pharyngitis or pharyngeal
      abscess. Pannus formation around the dens (odontoid) resulted in ventral
      compression of the craniocervical junction in each of these patients.
      Highlighting the hypermobility that causes such lesions, following fusion, the
      pannus and symptoms in several patients were diminished. Impairment of normal
      cerebrospinal fluid circulation out of the fourth ventricle and across the
      craniocervical junction appears to be a plausible endpoint in this discussion and
      a suitable explanation for some patients with CIM. Still, the mechanisms by which
      cerebrospinal fluid circulation is compromised may be variable and are not well
      understood. This is the first study dedicated to the evaluation of pannus
      formation in the CIM population. We hypothesize that pharyngeal inflammatory
      conditions contribute to the formation and progression of hindbrain herniation in
      a small subset of patients with CIMs.

PMID- 25974329
TI  - Hippocampal memory enhancing activity of pine needle extract against scopolamine
      induced amnesia in a mouse model.
AB  - We evaluated the neuropharmacological effects of 30% ethanolic pine needle
      extract (PNE) on memory impairment caused by scopolamine injection in mice
      hippocampus. Mice were orally pretreated with PNE (25, 50, and 100 mg/kg) or
      tacrine (10 mg/kg) for 7 days, and scopolamine (2 mg/kg) was injected
      intraperitoneally, 30 min before the Morris water maze task on first day. To
      evaluate memory function, the Morris water maze task was performed for 5 days
      consecutively. Scopolamine increased the escape latency and cumulative path
      length but decreases the time spent in target quadrant, which were ameliorated by
      pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase
      activity, neurogenesis and their connecting pathway were abnormally altered by
      scopolamine in hippocampus and/or sera, while those alterations were recovered by
      pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were
      ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased
      the proliferating cells and immature neurons against hippocampal neurogenesis
      suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained
      cells. The expression of brain-derived neurotrophic factor (BDNF) and
      phosphorylated cAMP response element-binding protein (pCREB) in both protein and
      gene were facilitated by PNE pretreatment. These findings suggest that PNE could
      be a potent neuropharmacological drug against amnesia, and its possible mechanism
      might be modulating cholinergic activity via CREB-BDNF pathway.

PMID- 25974331
TI  - Thyroid function is associated with non-alcoholic fatty liver disease in chronic
      hepatitis B-infected subjects.
AB  - BACKGROUND AND AIMS: Associations between thyroid function and non-alcoholic
      fatty liver disease (NAFLD) are unknown in chronic hepatitis B (CHB)-infected
      patients. Thus, the aim of the study was to investigate the prevalence of thyroid
      dysfunction and its relationship with NAFLD in CHB. METHODS: Consecutive naive
      CHB infected patients that had undergone liver biopsy and serum thyroid function
      tests between January 2007 and December 2011 were retrospective analyzed. NAFLD
      was diagnosed as at least 5% biopsy-proven hepatic steatosis without significant
      alcohol consumption. RESULTS: A total of 1154 non-alcoholics with CHB were
      included, 270 (23.39%) patients were found to have NAFLD, most of them (88.5%)
      with mild steatosis. The prevalence of hyperthyroidism and hypothyroidism
      (including subclinical and overt) was 1.56% and 1.64%, respectively, both with
      similar rates in patients with and without NAFLD (1.85% vs 1.47%, 1.48% vs 1.69%,
      respectively, both P > 0.05). The serum thyroid-stimulating hormone (TSH) level
      in NAFLD patients was significantly higher than that in patients without NAFLD
      (2.22 +/- 2.13 vs 1.61 +/- 1.20 mIU/L, P < 0.05). After adjustment for age and
      gender, the elevated TSH level was associated with increased odds of having
      steatosis (odds ratio1.54, 95% confidence interval 1.049-2.271) instead of viral
      factors and hepatic inflammation and fibrosis. CONCLUSIONS: Thyroid dysfunction
      is not common in CHB-infected patients, and the prevalence of hypothyroidism in
      CHB individuals with or without NAFLD is similar. However, increased serum TSH
      concentration at the normal range is a significant predictor of hepatic steatosis
      in patients with CHB.

PMID- 25974332
TI  - Quantitative mapping of the per-axon diffusion coefficients in brain white
      matter.
AB  - PURPOSE: This article presents a simple method for estimating the effective
      diffusion coefficients parallel and perpendicular to the axons unconfounded by
      the intravoxel fiber orientation distribution. We also call these parameters the
      per-axon or microscopic diffusion coefficients. THEORY AND METHODS: Diffusion MR
      imaging is used to probe the underlying tissue material. The key observation is
      that for a fixed b-value the spherical mean of the diffusion signal over the
      gradient directions does not depend on the axon orientation distribution. By
      exploiting this invariance property, we propose a simple, fast, and robust
      estimator of the per-axon diffusion coefficients, which we refer to as the
      spherical mean technique. RESULTS: We demonstrate quantitative maps of the axon
      scale diffusion process, which has factored out the effects due to fiber
      dispersion and crossing, in human brain white matter. These microscopic diffusion
      coefficients are estimated in vivo using a widely available off-the-shelf pulse
      sequence featuring multiple b-shells and high-angular gradient resolution.
      CONCLUSION: The estimation of the per-axon diffusion coefficients is essential
      for the accurate recovery of the fiber orientation distribution. In addition, the
      spherical mean technique enables us to discriminate microscopic tissue features
      from fiber dispersion, which potentially improves the sensitivity and/or
      specificity to various neurological conditions. Magnetic Resonance in Medicine
      published by Wiley Periodicals, Inc.

PMID- 25974334
TI  - Traveling bands for the Keller-Segel model with population growth.
AB  - This paper is concerned with the existence of the traveling bands to the Keller
      Segel model with cell population growth in the form of a chemical uptake
      kinetics. We find that when the cell growth is considered, the profile of
      traveling bands, the minimum wave speed and the range of the chemical consumption
      rate for the existence of traveling wave solutions will change. Our results
      reveal that collective interaction of cell growth and chemical consumption rate
      plays an essential role in the generation of traveling bands. The research in the
      paper provides new insights into the mechanisms underlying the chemotactic
      pattern formation of wave bands. 

PMID- 25974333
TI  - Sleep apnea in patients reporting insomnia or restless legs symptoms.
AB  - OBJECTIVE: Insomnia and restless legs syndrome (RLS) are defined by self-reported
      symptoms, and polysomnography (PSG) is not routinely indicated. Occult
      obstructive sleep apnea (OSA), common even in asymptomatic adults, may complicate
      management of patients presenting with insomnia or restless legs. To this end, we
      investigated objective sleep apnea metrics in a large retrospective cohort
      according to self-reported symptom profiles. METHODS: We compared sleep apnea
      findings in patients referred to our center according to self-reported symptoms
      associated with insomnia, sleep apnea, and restless legs. The cohort included
      over 1900 adults who underwent diagnostic (n = 1418) or split-night (n = 504)
      PSGs and completed a symptom and medical history questionnaire. RESULTS: More
      than 30% of patients who did not endorse any OSA symptoms, but did endorse
      insomnia or restless legs symptoms, were found to have OSA based on apnea
      hypopnea index (AHI) >5 during overnight laboratory testing. Regression models of
      the full cohort showed that the risk of OSA was related, as expected, to older
      age, male sex, elevated body mass index, and presence of OSA symptoms. The
      presence of insomnia symptoms did not alter the risk of OSA. The presence of
      restless legs symptoms showed a small odds ratio for lowered OSA risk.
      CONCLUSIONS: Objective evidence of OSA occurs similarly in those with insomnia or
      restless legs symptoms, even among those without self-reported OSA symptoms.
      Providers should be aware of the potential for occult OSA in populations with
      insomnia and restless legs, which may complicate their management in addition to
      presenting an independent medical risk itself.

PMID- 25974335
TI  - A nosocomial epidemic model with infection of patients due to contaminated rooms.
AB  - A model of epidemic bacterial infections in hospitals is developed. The model
      incorporates the infection of patients and the contamination of healthcare
      workers due to environmental causes. The model is analyzed with respect to the
      asymptotic behavior of solutions. The model is interpreted to provide insight for
      controlling these nosocomial epidemics. 

PMID- 25974336
TI  - Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing
      virus therapeutics.
AB  - The past century's description of oncolytic virotherapy as a cancer treatment
      involving specially-engineered viruses that exploit immune deficiencies to
      selectively lyse cancer cells is no longer adequate. Some of the most promising
      therapeutic candidates are now being engineered to produce immunostimulatory
      factors, such as cytokines and co-stimulatory molecules, which, in addition to
      viral oncolysis, initiate a cytotoxic immune attack against the tumor. This study
      addresses the combined effects of viral oncolysis and T-cell-mediated oncolysis.
      We employ a mathematical model of virotherapy that induces release of cytokine IL
      12 and co-stimulatory molecule 4-1BB ligand. We found that the model closely
      matches previously published data, and while viral oncolysis is fundamental in
      reducing tumor burden, increased stimulation of cytotoxic T cells leads to a
      short-term reduction in tumor size, but a faster relapse. In addition, we found
      that combinations of specialist viruses that express either IL-12 or 4-1BBL might
      initially act more potently against tumors than a generalist virus that
      simultaneously expresses both, but the advantage is likely not large enough to
      replace treatment using the generalist virus. Finally, according to our model and
      its current assumptions, virotherapy appears to be optimizable through targeted
      design and treatment combinations to substantially improve therapeutic outcomes. 

PMID- 25974337
TI  - Global stability of an age-structured virus dynamics model with Beddington
      DeAngelis infection function.
AB  - In this paper, we study an age-structured virus dynamics model with Beddington
      DeAngelis infection function. An explicit formula for the basic reproductive
      number R0 of the model is obtained. We investigate the global behavior of the
      model in terms of R0: if R0 <= 1, then the infection-free equilibrium is globally
      asymptotically stable, whereas if R0 > 1, then the infection equilibrium is
      globally asymptotically stable. Finally, some special cases, which reduce to some
      known HIV infection models studied by other researchers, are considered. 

PMID- 25974338
TI  - Special issue dedicated to the 70th birthday of Glenn F. Webb. Preface.
AB  - This special issue is dedicated to the 70th birthday of Glenn F. Webb. The topics
      of the 12 articles appearing in this special issue include evolutionary dynamics
      of population growth, spatio-temporal dynamics in reaction-diffusion biological
      models, transmission dynamics of infectious diseases, modeling of antibiotic
      resistant bacteria in hospitals, analysis of Prion models, age-structured models
      in ecology and epidemiology, modeling of immune response to infections, modeling
      of cancer growth, etc. These topics partially represent the broad areas of
      Glenn's research interest. 

PMID- 25974339
TI  - The work of Glenn F. Webb.
AB  - It is my distinct pleasure to introduce this volume honoring the 70th birthday of
      Professor Glenn F. Webb. The existence of this compiled volume is in itself a
      testimony of Glenn's dedication to, his pursuit of, and his achievement of
      scientific excellence. As we honor Glenn, we honor what is excellent in our
      profession. Aristotle clearly articulated his concept of excellence. ''We are
      what we repeatedly do. Excellence, then, is not an act, but a habit." As we look
      over the course of his career we observe ample evidence of Glenn Webb's habitual
      practice of excellence. Beginning with Glenn's first paper [1], one observes a
      constant stream of productivity and high impact work. Glenn has authored or co
      authored over 160 papers, written one research monograph, and co-edited six
      volumes. He has delivered plenary lectures, colloquia, and seminars across the
      globe, and he serves on the editorial boards of 11 archival journals. He is a
      Fellow of the American Mathematical Society. Glenn's scientific career chronicles
      an evolution of scientific work that began with his interest in nonlinear
      semigroup theory and leads up to his current activity in biomedical mathematics.
      At each stage we see seminal contributions in the areas of nonlinear semigroups,
      functional differential equations, infinite dimensional dynamical systems,
      mathematical population dynamics, mathematical biology and biomedical
      mathematics. Glenn's work is distinguished by a clarity and accessibility of
      exposition, a precise identification and description of the problem or model
      under consideration, and thorough referencing. He uses elementary methods
      whenever possible but couples this with an ability to employ power abstract
      methods when necessitated by the problem. 

PMID- 25974340
TI  - The evolutionary dynamics of a population model with a strong Allee effect.
AB  - An evolutionary game theoretic model for a population subject to predation and a
      strong Allee threshold of extinction is analyzed using, among other methods,
      Poincare-Bendixson theory. The model is a nonlinear, plane autonomous system
      whose state variables are population density and the mean of a phenotypic trait,
      which is subject to Darwinian evolution, that determines the population's
      inherent (low density) growth rate (fitness). A trade-off is assumed in that an
      increase in the inherent growth rate results in a proportional increase in the
      predator's attack rate. The main results are that orbits equilibrate (there are
      no cycles or cycle chains of saddles), that the extinction set (or Allee basin)
      shrinks when evolution occurs, and that the meant trait component of survival
      equilibria occur at maxima of the inherent growth rate (as a function of the
      trait). 

PMID- 25974341
TI  - Stability and persistence in ODE models for populations with many stages.
AB  - A model of ordinary differential equations is formulated for populations which
      are structured by many stages. The model is motivated by ticks which are vectors
      of infectious diseases, but is general enough to apply to many other species. Our
      analysis identifies a basic reproduction number that acts as a threshold between
      population extinction and persistence. We establish conditions for the existence
      and uniqueness of nonzero equilibria and show that their local stability cannot
      be expected in general. Boundedness of solutions remains an open problem though
      we give some sufficient conditions. 

PMID- 25974342
TI  - Mathematical probit and logistic mortality models of the Khapra beetle fumigated
      with plant essential oils.
AB  - In the current study, probit and logistic models were employed to fit
      experimental mortality data of the Khapra beetle, Trogoderma granarium (Everts)
      (Coleoptera: Dermestidae), when fumigated with three plant oils of the gens
      Achillea. A generalized inverse matrix technique was used to estimate the
      mortality model parameters instead of the usual statistical iterative maximum
      likelihood estimation. As this technique needs to perturb the observed mortality
      proportions if the proportions include 0 or 1, the optimal perturbation in terms
      of minimum least squares (L2) error was also determined. According to our
      results, it was better to log-transform concentration and time as explanatory
      variables in modeling mortality of the test insect. Estimated data using the
      probit model were more accurate in terms of L2 errors, than the logistic one.
      Results of the predicted mortality revealed also that extending the fumigation
      period could be an effective control strategy, even, at lower concentrations.
      Results could help in using a relatively safe and effective strategy for the
      control of this serious pest using alternative control strategy to reduce the
      health and environmental drawbacks resulted from the excessive reliance on the
      broadly toxic chemical pesticides and in order to contribute safeguard world-wide
      grain supplies. 

PMID- 25974343
TI  - Bifurcation analysis and transient spatio-temporal dynamics for a diffusive plant
      herbivore system with Dirichlet boundary conditions.
AB  - In this paper, we study a diffusive plant-herbivore system with homogeneous and
      nonhomogeneous Dirichlet boundary conditions. Stability of spatially homogeneous
      steady states is established. We also derive conditions ensuring the occurrence
      of Hopf bifurcation and steady state bifurcation. Interesting transient spatio
      temporal behaviors including oscillations in one or both of space and time are
      observed through numerical simulations. 

PMID- 25974344
TI  - Optimal design for parameter estimation in EEG problems in a 3D multilayered
      domain.
AB  - The fundamental problem of collecting data in the ''best way'' in order to assure
      statistically efficient estimation of parameters is known as Optimal Experimental
      Design. Many inverse problems consist in selecting best parameter values of a
      given mathematical model based on fits to measured data. These are usually
      formulated as optimization problems and the accuracy of their solutions depends
      not only on the chosen optimization scheme but also on the given data. We
      consider an electromagnetic interrogation problem, specifically one arising in an
      electroencephalography (EEG) problem, of finding optimal number and locations for
      sensors for source identification in a 3D unit sphere from data on its boundary.
      In this effort we compare the use of the classical D-optimal criterion for
      observation points as opposed to that for a uniform observation mesh. We consider
      location and best number of sensors and report results based on statistical
      uncertainty analysis of the resulting estimated parameters. 

PMID- 25974345
TI  - Global stability for the prion equation with general incidence.
AB  - We consider the so-called prion equation with the general incidence term
      introduced in [14], and we investigate the stability of the steady states. The
      method is based on the reduction technique introduced in [11]. The argument
      combines a recent spectral gap result for the growth-fragmentation equation in
      weighted L1 spaces and the analysis of a nonlinear system of three ordinary
      differential equations. 

PMID- 25974346
TI  - An age-structured model for the coupled dynamics of HIV and HSV-2.
AB  - Evidence suggests a strong correlation between the prevalence of HSV-2 (genital
      herpes) and the perseverance of the HIV epidemic. HSV-2 is an incurable viral
      infection, characterized by periodic reactivation. We construct a model of the co
      infection dynamics between the two diseases by incorporating a time-since
      infection variable to track the alternating periods of infectiousness of HSV-2.
      The model considers only heterosexual relationships and distinguishes three
      population groups: males, general population females, and female sex workers. We
      calculate the basic reproduction numbers for each disease that provide threshold
      conditions, which determine whether a disease dies out or becomes endemic in the
      absence of the other disease. We also derive the invasion reproduction numbers
      that determine whether or not a disease can invade into a population in which the
      other disease is endemic. The calculations of the invasion reproduction numbers
      suggest a new aspect in their interpretation - the class from which the initial
      disease carrier arises is important for understanding the invasion dynamics and
      biological interpretation of the expressions of the reproduction numbers.
      Sensitivity analysis is conducted to examine the role of model parameters in
      influencing the model outcomes. The results are discussed in the last section. 

PMID- 25974347
TI  - Mathematically modeling the biological properties of gliomas: A review.
AB  - Although mathematical modeling is a mainstay for industrial and many scientific
      studies, such approaches have found little application in neurosurgery. However,
      the fusion of biological studies and applied mathematics is rapidly changing this
      environment, especially for cancer research. This review focuses on the exciting
      potential for mathematical models to provide new avenues for studying the growth
      of gliomas to practical use. In vitro studies are often used to simulate the
      effects of specific model parameters that would be difficult in a larger-scale
      model. With regard to glioma invasive properties, metabolic and vascular
      attributes can be modeled to gain insight into the infiltrative mechanisms that
      are attributable to the tumor's aggressive behavior. Morphologically, gliomas
      show different characteristics that may allow their growth stage and invasive
      properties to be predicted, and models continue to offer insight about how these
      attributes are manifested visually. Recent studies have attempted to predict the
      efficacy of certain treatment modalities and exactly how they should be
      administered relative to each other. Imaging is also a crucial component in
      simulating clinically relevant tumors and their influence on the surrounding
      anatomical structures in the brain. 

PMID- 25974348
TI  - Studying microbiology with Glenn F. Webb.
AB  - I began working with Glenn F. Webb in 1997. At that time, I was on the faculty of
      Vanderbilt University, in the School of Medicine, in the Department of Medicine,
      in its Division of Infectious Diseases. As with mathematics, modern medicine has
      its different disciplines (e.g. Surgery and Internal Medicine), and then further
      subdivisions (e.g. Cardiology and Infectious Diseases). Within Internal Medicine,
      most of the divisions are based on the treatment of conditions that relate to a
      single organ or group of organs -- the heart, the lungs, the kidneys, the
      digestive system. But the discipline of Infectious Diseases was based on a
      different concept: the war between humans and microbes. 

PMID- 25974349
TI  - Pd-Catalyzed Diamination of 1,2,4-Triazinyl Complexant Scaffolds.
AB  - As part of ongoing efforts in this laboratory to design and synthesize
      multidentate soft-N-donors as effective complexants for chemoselective minor
      actinide extraction from used nuclear fuel, a series of aminated mono-1,2,4
      triazinylpyridines were required. This study focuses on streamlining convergent
      access to a diverse array of functionalized N-donors using Pd-catalysis from a
      common synthon affording access to pyridinyl triazines as the 4,4'-amino
      derivatives which are commercially limited and unsuccessful in traditional
      condensation chemistry. A general Pd-catalyzed method for the double amination of
      functionalized pyridinyl-1,2,4-triazines with low catalyst/ligand loadings
      enabling the formation of 16 novel complexants is presented. 

PMID- 25974351
TI  - Effect of non-enzymatic proteins on enzymatic hydrolysis and simultaneous
      saccharification and fermentation of different lignocellulosic materials.
AB  - Non-enzymatic proteins were added during hydrolysis of cellulose and simultaneous
      saccharification and fermentation (SSF) of different biomass materials. Bovine
      serum albumin (BSA), a model non-enzymatic protein, increased cellulose and
      xylose conversion efficiency and also enhanced the ethanol yield during SSF of
      rice straw subjected to varied pretreatments. Corn steep liquor, yeast extract,
      and peptone also exerted a similar effect as BSA and enhanced the enzymatic
      hydrolysis of rice straw. Compared to the glucose yields obtained after enzymatic
      hydrolysis of rice straw in the absence of additives, the glucose yields after
      72h of hydrolysis increased by 12.7%, 13.5%, and 13.7% after addition of the corn
      steep liquor, yeast extract, and peptone, respectively. This study indicated the
      use of BSA as an alternative to intensive pretreatment of lignocellulosic
      materials for enhancing enzymatic digestibility. The utilization of non-enzymatic
      protein additives is promising for application in glucose and ethanol production
      from lignocellulosic materials. 

PMID- 25974350
TI  - Plasma metabolomic profiling of patients with diabetes-associated cognitive
      decline.
AB  - Diabetes related cognitive dysfunction (DACD), one of the chronic complications
      of diabetes, seriously affect the quality of life in patients and increase family
      burden. Although the initial stage of DACD can lead to metabolic alterations or
      potential pathological changes, DACD is difficult to diagnose accurately.
      Moreover, the details of the molecular mechanism of DACD remain somewhat elusive.
      To understand the pathophysiological changes that underpin the development and
      progression of DACD, we carried out a global analysis of metabolic alterations in
      response to DACD. The metabolic alterations associated with DACD were first
      investigated in humans, using plasma metabonomics based on high-performance
      liquid chromatography coupled with quadrupole time-of-flight tandem mass
      spectrometry and multivariate statistical analysis. The related pathway of each
      metabolite of interest was searched in database online. The network diagrams were
      established KEGGSOAP software package. Receiver operating characteristic (ROC)
      analysis was used to evaluate diagnostic accuracy of metabolites. This is the
      first report of reliable biomarkers of DACD, which were identified using an
      integrated strategy. The identified biomarkers give new insights into the
      pathophysiological changes and molecular mechanisms of DACD. The disorders of
      sphingolipids metabolism, bile acids metabolism, and uric acid metabolism pathway
      were found in T2DM and DACD. On the other hand, differentially expressed plasma
      metabolites offer unique metabolic signatures for T2DM and DACD patients. These
      are potential biomarkers for disease monitoring and personalized medication
      complementary to the existing clinical modalities. 

PMID- 25974352
TI  - Screening of a microbial consortium for highly simultaneous degradation of
      lignocellulose and chlorophenols.
AB  - In this work, spent mushroom substrates were utilized for screening a microbial
      consortium with highly simultaneous degradation of lignocellulose and
      chlorophenols. The desired microbial consortium OEM1 was gained through
      successive cultivation for about 50 generations and its stability of composition
      was verified by denaturing gradient gel electrophoresis (DGGE) during screening
      process. It could degrade lignocellulose and chlorophenols at around 50% and
      100%, respectively, within 7days. The diversity analysis and the growth
      characteristics of OEM1 during degradation process were investigated by PCR-DGGE
      combined with clone and sequence. The results indicated that OEM1 consisted of 31
      strains. Proteobacteria and Bacteroidetes were the predominant bacterial groups.
      The dynamic change of OEM1 illustrated that consortium community structure was
      effected by pH and substrate alteration and tended to be stable after 6days'
      cultivation. Furthermore, bacteria (11 strains) and actinomycetes (2 strains)
      were obtained based on plate isolation and identified via 16S rDNA sequence. 

PMID- 25974353
TI  - Caecal tumor biopsy with a rigid sigmoidoscope - Ileorectal intussusception.
AB  - INTRODUCTION: Ileorectal intussusception is a rare condition in adults in which
      the distal ileum, caecum, variable lengths of ascending and transvers colon, and
      associated mesentery invaginate into the rectum. PRESENTATION OF CASE: We present
      the case of a 56 year old man who presented to our hospital for investigation of
      vague symptoms including small volumes of bright red rectal bleeding and colicky
      abdominal pain. He was found on CT scanning to have an extensive ileorectal
      intussusception and extensive liver metastasis. An emergency laparotomy was
      performed due to the concern of bowel ischaemia. No evidence of bowel ischaemia
      was found. The intussusceptum was carefully reduced and an extended right
      hemicolectomy with a primary anastomosis was performed. The patient recovered
      well and was discharged home six days post operatively. DISCUSSION:
      Intussusceptions are rare in the adult population. They may not present with the
      classical triad of crampy abdominal pain, vomiting, and bloody stools and
      radiological imaging plays a key role in diagnosis. Intussusception in adults is
      usually secondary to malignancy and operative management needs to take into
      account the risk of upstaging the disease. In the face of pre-existing
      metastasis, preserving bowel length should be considered; however, there is no
      high level evidence to guide decision-making. CONCLUSION: Intussusception is a
      diagnosis that needs to be considered in the adult population. Diagnosis largely
      depends on radiological imaging, especially CT scanning. The operative management
      is variable and should be determined on a case by case basis.

PMID- 25974354
TI  - Glossopharyngeal neuralgia associated with cardiac syncope: Two case reports and
      literature review.
AB  - INTRODUCTION: Vago-glossopharyngeal neuralgia is an unusual clinical syndrome
      characterized by paroxysms of sharp pain in the distribution of glossopharyngeal
      nerve. Rarely the condition is associated with arrhythmia and cardiac syncope, a
      phenomenon named vagoglossopharyngeal neuralgia. PRESENTATION OF CASES: Here we
      present two patients with glosopharyngeal neuralgia associated with repetitive
      episodes of syncope referred from their primary care physician to neurosurgery
      department of a general hospital in Crete, Greece. The patients were successfully
      treated with microvascular decompression. DISCUSSION: A literature review on
      pathogenesis, diagnosis and management is also performed. CONCLUSIONS: Surgeons
      as well as primary care physicians have to be aware of this rare condition in
      order to prevent associated life-threatening complications and improve patient's
      clinical status with accurate therapy.

PMID- 25974355
TI  - Factors that condition the spontaneous reporting of adverse drug reactions among
      nurses: an integrative review.
AB  - AIM: To describe and synthesise previous research on factors conditioning the
      spontaneous reporting of adverse drug reactions among nurses. BACKGROUND:
      Spontaneous reports of adverse drug reactions by health-care providers, are a
      main instrument for the continuous evaluation of the risk-benefit ratio of every
      drug. Under-reporting of adverse drug reactions by all health-care providers, in
      particular by nurses, is a major limitation to this system. EVALUATION: An
      integrated review of the literature was conducted using MEDLINE, CINAHL, Embase,
      Scopus databases and Google Scholar. After evaluation for appropriateness related
      to inclusion/exclusion criteria, 16 studies were included in the final analysis
      and synthesis. KEY ISSUES: Two factors emerged from the study: (1) intrinsic
      factors related to nurses' knowledge and attitudes; (2) extrinsic factors related
      to nurses' interaction with health-care organisations and to the relationship
      between nurses and physicians. Nurses' attitudes that hinder reporting include
      ignorance, insecurity, fear and lethargy. CONCLUSIONS: Nurses are not fully aware
      of their role in adverse drug reaction reporting. Nurses must acquire greater
      knowledge to implement specific skills into their daily clinical practice.
      IMPLICATIONS FOR NURSING MANAGEMENT: To improve nurses' reporting of adverse drug
      reactions, it is necessary to develop management approaches that modify both
      intrinsic and extrinsic factors.

PMID- 25974356
TI  - Toxicity of concomitant cetuximab and radiotherapy with or without initial taxane
      based induction chemotherapy in locally advanced head and neck cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the tolerability of
      concurrent radiotherapy and cetuximab (bioradiotherapy [BRT]) after taxane-based
      induction chemotherapy in head and neck squamous cell carcinoma (HNSCC). METHODS:
      One hundred four patients with HNSCC received BRT with (29%) or without (71%)
      prior taxane-based induction chemotherapy. RESULTS: Radiodermatitis (97%) and
      skin rash (65%) occurred frequently, but there was no difference of occurrence or
      the grade of the rash observed in the 2 populations. However, patients receiving
      taxane-based induction chemotherapy had a less severe rash as compared with
      patients without induction chemotherapy. Mucositis and dysphagia were frequent
      and comparable in the 2 groups. The occurrence of a skin rash (at any grade) did
      not predict an increased overall survival (OS) in the overall population, but it
      was associated with an improved 3-year OS in patients receiving taxane-based
      induction chemotherapy. OS was not influenced by the skin rash grade in the
      overall population of the 2 treatment subgroups. CONCLUSION: Taxane-based
      induction chemotherapy did not increase the rate of cetuximab-related toxicities.
      (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E905-E910, 2016.

PMID- 25974357
TI  - Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1
      Mutations.
AB  - IMPORTANCE: Somatic mutations in BAP1 (BRCA1-associated protein 1 gene) are
      frequently identified in uveal melanoma. To date, the role of germline BAP1
      mutations in uveal melanoma has not been characterized. OBJECTIVE: To
      characterize the clinical phenotype of uveal melanoma in patients with germline
      BAP1 mutations. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at
      an academic ophthalmology referral center among 507 patients with uveal melanoma
      who consented for collection of blood samples. The study dates were June 22,
      1992, to December 14, 2010. MAIN OUTCOMES AND MEASURES: Clinical characteristics
      of uveal melanoma and the development of metastases. BAP1 gene sequencing from
      blood samples of patients with uveal melanoma was correlated with clinical
      characteristics. RESULTS: Of 507 blood samples analyzed, 25 patients (4.9%)
      exhibited 18 BAP1 polymorphisms, of which 9 were novel. Computational analyses
      predicted that 8 BAP1 mutations in 8 patients (1.6%) were likely to result in
      damaged BAP1 protein. Five of these 8 mutations were novel. These 8 patients were
      compared with 482 patients in whom no BAP1 polymorphisms were identified. In
      univariate analyses, patients with germline BAP1 mutations exhibited larger tumor
      diameters (mean, 15.9 vs 12.3 mm; P = .004) and higher rates of ciliary body
      involvement (75.0% vs 21.6%, P = .002) and metastases (71.4% vs 18.0%, P = .003)
      compared with control subjects. Patients with germline BAP1 mutations exhibited
      increased frequency of family history of cancer (100% vs 65.9%, P = .06),
      particularly cutaneous melanoma (62.5% vs 9.9%, P < .001) and ocular melanoma
      (25.0% vs 1.9%, P = .01). No differences were identified in age at diagnosis,
      sex, history of other malignant neoplasm, presenting visual acuity, distance of
      the tumor from the optic nerve or fovea, iris involvement, extrascleral
      extension, or tumor pigmentation. Germline BAP1 mutations increased risk of
      metastasis independent of ciliary body involvement (P = .02). Germline BAP1
      mutation approached significance as an independent risk factor for metastasis (P
      = .09). CONCLUSIONS AND RELEVANCE: These data suggest that germline BAP1
      mutations occur infrequently in uveal melanoma and are associated with larger
      tumors and higher rates of ciliary body involvement, 2 known risk factors for
      metastasis.

PMID- 25974358
TI  - Glycans in Medicinal Chemistry: An Underexploited Resource.
AB  - The biological relevance of glycans as mediators of key physiological processes,
      including disease-related mechanisms, makes them attractive targets for a wide
      range of medical applications. Despite their important biological roles,
      especially as molecular recognition elements, carbohydrates have not been fully
      exploited as therapeutics mainly due to the scarcity of structure-activity
      correlations and their non-drug-like properties. A more detailed understanding of
      the complex carbohydrate structures and their associated functions should
      contribute to the development of new glycan-based pharmaceuticals. Recent
      significant progress in oligosaccharide synthesis and chemical glycobiology has
      renewed the interest of the medicinal chemistry community in carbohydrates. This
      promises to increase our possibilities to harness them in drug discovery efforts
      for the development of new and more effective, synthetic glycan-based
      therapeutics and vaccines. 

PMID- 25974359
TI  - Improving diabetic foot examination performance using electronic medical record
      tools in a specialty clinic.

PMID- 25974360
TI  - Patient-generated health data foundation for personalized collaborative care.

PMID- 25974361
TI  - Predicting nurses' use of healthcare technology using the technology acceptance
      model: an integrative review.
AB  - The benefits of healthcare technologies can only be attained if nurses accept and
      intend to fully use them. One of the most common models utilized to understand
      user acceptance of technology is the Technology Acceptance Model. This model and
      modified versions of it have only recently been applied in the healthcare
      literature among nurse participants. An integrative literature review was
      conducted on this topic. Ovid/MEDLINE, PubMed, Google Scholar, and CINAHL were
      searched yielding a total of 982 references. Upon eliminating duplicates and
      applying the inclusion and exclusion criteria, the review included a total of
      four dissertations, three symposium proceedings, and 13 peer-reviewed journal
      articles. These documents were appraised and reviewed. The results show that a
      modified Technology Acceptance Model with added variables could provide a better
      explanation of nurses' acceptance of healthcare technology. These added variables
      to modified versions of the Technology Acceptance Model are discussed, and the
      studies' methodologies are critiqued. Limitations of the studies included in the
      integrative review are also examined. 

PMID- 25974363
TI  - Densely Substituted L-Proline Esters as Catalysts for Asymmetric Michael
      Additions of Ketones to Nitroalkenes.
AB  - Homochiral methyl 4-aminopyrrolidine-2-carboxylates are readily obtained by means
      of asymmetric (3 + 2) cycloadditions between azomethine ylides and nitroalkenes,
      followed by catalytic hydrogenation of the intermediate 4-nitro cycloadducts.
      These 4-aminopyrrolidine-2-carboxylate esters belong to the L-series of natural
      amino acids and catalyze asymmetric Michael additions of ketones to nitroalkenes.
      However, the enantioselectivity observed with these novel unnatural
      organocatalysts is opposite to that obtained with L-proline. Since both 4-nitro
      and 4-amino L-proline esters are efficient organocatalysts of aldol reactions,
      these results permit to modulate asymmetric quimioselective aldol and conjugate
      addition reactions.

PMID- 25974364
TI  - Day Hospital Treatment for Anorexia Nervosa: A 12-Month Follow-up Study.
AB  - Day hospitals (DHs) represent a treatment option for anorexia nervosa (AN), a
      mental disorder that is difficult to treat and has no evidence-based treatments
      available. We aimed to determine the effectiveness of a DH treatment that was
      specifically focused on the emotions of severe AN patients. Body mass index and
      eating psychopathology were the primary outcome measures. Fifty-six adult
      patients with AN were assessed upon admission, at the end of treatment (EOT) and
      at a 12-month follow-up evaluation (T18) using Eating Disorders Inventory-2, Beck
      Depression Inventory, Hamilton Rating Scale for Anxiety and Brief Social Phobia
      Scale. All participants received a multidisciplinary treatment programme that
      focused on psychodynamic psychotherapy. Seventy-eight per cent of participants
      reported positive outcomes at EOT and 68% at T18. Moreover, 82.1% and 65.4% of
      long-standing patients showed positive outcomes at EOT and T18, respectively. All
      measures of psychopathology were significantly improved at EOT and were
      maintained at follow-up. Our DH was effective at treating severe AN patients;
      however, further investigations of the processes of change are warranted.

PMID- 25974365
TI  - Spin-state transition in unstrained & strained ultra-thin BiCoO3 films.
AB  - Using first principles density functional theory (DFT) based calculations
      supplemented with the Hubbard U term (DFT+U), we theoretically study the
      structural, electronic and magnetic properties of ultra-thin films of a
      perovskite compound BiCoO(3), constructed along the [001] direction under ambient
      conditions. Our study shows that significant structural change occurs in thin
      film geometry compared to bulk, which modifies the local oxygen coordination
      around the Co ion from a square pyramidal environment in the bulk phase to an
      octahedral environment in the thin-film structure. This changes the high-spin
      state of Co(3+) in bulk to the low-spin state of Co(3+) ions in the thin-film
      geometry. The influence of both tensile and compressive strain on the structural
      and electronic properties of the thin-film is studied. Our study shows a layer
      selective transition of the Co(3+) spin state when subjected to tensile strain,
      which is found to be driven by the change in the Bi environment. Our theoretical
      study should motivate the experimental investigation of the thin film of
      BiCoO(3).

PMID- 25974366
TI  - Hydrogen sulfide alleviates toxic effects of arsenate in pea seedlings through up
      regulation of the ascorbate-glutathione cycle: Possible involvement of nitric
      oxide.
AB  - In plants, hydrogen sulfide (H2S) is an emerging novel signaling molecule that is
      involved in growth regulation and abiotic stress responses. However, little is
      known about its role in the regulation of arsenate (As(V)) toxicity. Therefore,
      hydroponic experiments were conducted to investigate whether sodium hydrosulfide
      (NaHS; a source of H2S) is involved in the regulation of As(V) toxicity in pea
      seedlings. Results showed that As(V) caused decreases in growth, photosynthesis
      (measured as chlorophyll fluorescence) and nitrogen content, which was
      accompanied by the accumulation of As. As(V) treatment also reduced the
      activities of cysteine desulfhydrase and nitrate reductase, and contents of H2S
      and nitric oxide (NO). However, addition of NaHS ameliorated As(V) toxicity in
      pea seedlings, which coincided with the increased contents of H2S and NO. The
      cysteine level was higher under As(V) treatment in comparison to all other
      treatments (As-free; NaHS; As(V)+NaHS). The content of reactive oxygen species
      (ROS) and damage to lipids, proteins and membranes increased by As(V) while NaHS
      alleviated these effects. Enzymes of the ascorbate-glutathione cycle (AsA-GSH
      cycle) showed inhibition of their activities following As(V) treatment while
      their activities were increased by application of NaHS. The redox status of
      ascorbate and glutathione was disturbed by As(V) as indicated by a steep decline
      in their reduced/oxidized ratios. However, simultaneous NaHS application restored
      the redox status of the ascorbate and glutathione pools. The results of this
      study demonstrated that H2S and NO might both be involved in reducing the
      accumulation of As and triggering up-regulation of the AsA-GSH cycle to
      counterbalance ROS-mediated damage to macromolecules. Furthermore, the results
      suggest a crucial role of H2S in plant priming, and in particular for pea
      seedlings in mitigating As(V) stress. 

PMID- 25974367
TI  - Characterization of a novel cyclase-like gene family involved in controlling
      stress tolerance in rice.
AB  - A novel cyclase-like gene family (CYL) encodes proteins containing cyclase
      domain, but their functions are largely unknown. We report the systematic
      identification and characterization of CYL genes in the rice genome. Five
      putative CYL protein sequences (OsCYL1 to 4b) were identified. These sequences
      and other CYL homologs were classified into four subgroups based on phylogenetic
      analysis. Distinct diversification of these CYL proteins exists between plants
      and non-plants. The CYL family has conserved exon-intron structures, and the
      organizations of putative motifs in plants are specifically diverse. All OsCYL
      genes were expressed in a wide range of tissues or organs and were responsive to
      at least one of the abiotic stresses and hormone treatments applied. Protein
      OsCYL4a is targeted to the cell membrane. The overexpression of one stress
      responsive gene OsCYL4a in rice resulted in decreased tolerance to salt, drought,
      cold, and oxidative stress. The expression levels of some abiotic stress
      responsive factors, including H2O2-accumulating negative factors DST and OsSKIPa
      in OsCYL4a-overexpressing plants, were reduced compared with the wild type under
      normal condition and drought stress. These results suggest that rice CYL family
      may be functionally conserved polyketide cyclase, resulting in the rapid
      accumulation of reactive oxygen species to decrease tolerance to abiotic
      stresses. 

PMID- 25974368
TI  - The cold response of CBF genes in barley is regulated by distinct signaling
      mechanisms.
AB  - Cold acclimation ability is crucial in the winter survival of cereals. In this
      process CBF transcription factors play key role, therefore understanding the
      regulation of these genes might provide useful knowledge for molecular breeding.
      In the present study the signal transduction pathways leading to the cold
      induction of different CBF genes were investigated in barley cv. Nure using
      pharmacological approach. Our results showed that the cold induced expression of
      CBF9 and CBF14 transcription factors is regulated by phospholipase C,
      phospholipase D pathways and calcium. On the contrary, these pathways have
      negative effect on the cold induction of CBF12 that is regulated by a different,
      as yet unidentified pathway. The diversity in the regulation of these
      transcription factors corresponds to their sequence based phylogenetic
      relationships suggesting that their evolutionary separation happened on
      structural, functional and regulational levels as well. On the CBF effector gene
      level, the signaling regulation is more complex, resultant effect of multiple
      pathways. 

PMID- 25974369
TI  - Stuck between a ROS and a hard place: Analysis of the ubiquitin proteasome
      pathway in selenocysteine treated Brassica napus reveals different toxicities
      during selenium assimilation.
AB  - During the selenium assimilation pathway, inorganic selenate and selenite are
      reduced to form selenocysteine (Sec). Tolerance to selenium in plants has long
      been attributable to minimizing the replacement of cysteine with selenocysteine,
      which can result in nonspecific selenoproteins that are potentially misfolded.
      Despite this widely accepted assumption, there is no evidence in higher plants
      demonstrating that selenocysteine induces toxicity by resulting in malformed
      proteins. In this study, we use Brassica napus to analyze the ubiquitin
      proteasome pathway, which is capable of removing misfolded proteins. Sec rapidly
      increased proteasome activity and levels of ubiquitinated proteins, strongly
      indicating that selenocysteine induces protein misfolding. Proteasome inhibition
      increased the amount of selenium in protein in Sec-treated plants. Collectively,
      these data provide a mechanism that accounts for Sec toxicity. Additionally, Sec
      did not cause oxidative stress as judged by examining levels of superoxide using
      fluorescent microscopy. Therefore, the cellular response to Sec is different
      compared to selenite, which was recently shown to increase antioxidant metabolism
      in response to elevated mitochondrial superoxide that ultimately impaired
      proteasome activity. Therefore, plants must contend with two divergent modes of
      cytotoxicity during selenium assimilation. Selenite can result in oxidative
      stress, but increased flux of selenite reduction can yield Sec that in turn can
      cause protein misfolding. 

PMID- 25974370
TI  - Retrograde signaling between plastid and nucleus: A review.
AB  - Retrograde signaling, defined as the signaling events leading from the plastids
      to the nucleus, coordinates the expression of plastid and nuclear genes and is
      crucial for metabolic as well as developmental processes of the plastids. In the
      recent past, the identification of various components that are involved in the
      generation and transmission of plastid-originated retrograde signals and the
      regulation of nuclear gene expression has only provided a glimpse of the plastid
      retrograde signaling network, which remains poorly understood. The basic
      assumptions underlying our current understanding of retrograde signaling stayed
      untouched for many years. Therefore, an attempt has been made in this review
      article to summarize established facts and recent advances regarding various
      retrograde signaling pathways derived from different sources, the identification
      of key elements mediating retrograde signal transduction and also to give an
      overview of possible signaling molecules that remain to be investigated. 

PMID- 25974371
TI  - Glucose Sensing in Supramolecular Chemistry.

PMID- 25974372
TI  - Superior Lithium-Ion Storage Properties of Mesoporous CuO-Reduced Graphene Oxide
      Composite Powder Prepared by a Two-Step Spray-Drying Process.
AB  - Mesoporous CuO-reduced graphene oxide (rGO) composite powders were prepared by
      using a two-step spray-drying process. In the first step, hollow CuO powders were
      prepared from a spray solution of copper nitrate trihydrate with citric acid and
      were wet milled to obtain a colloidal spray solution. In the second step, spray
      drying of the colloidal solution that contained dispersed GO nanosheets produced
      mesoporous CuO-rGO composite powders with particle sizes of several microns.
      Thermal reduction of GO nanosheets to rGO nanosheets occurred during post
      treatment at 300  degrees C. Initial discharge capacities of the hollow CuO, bare
      CuO aggregate, and CuO-rGO composite powders at a current density of 2 A g(-1)
      were 838, 1145, and 1238 mA h g(-1) , respectively. Their discharge capacities
      after 200 cycles were 259, 380, and 676 mA h g(-1) , respectively, and their
      corresponding capacity retentions measured from the second cycle were 67, 48, and
      76 %, respectively. The mesoporous CuO-rGO composite powders have high structural
      stability and high conductivity because of the rGO nanosheets, and display good
      cycling and rate performances. 

PMID- 25974373
TI  - Pteros 2.0: Evolution of the fast parallel molecular analysis library for C++ and
      python.
AB  - Pteros is the high-performance open-source library for molecular modeling and
      analysis of molecular dynamics trajectories. Starting from version 2.0 Pteros is
      available for C++ and Python programming languages with very similar interfaces.
      This makes it suitable for writing complex reusable programs in C++ and simple
      interactive scripts in Python alike. New version improves the facilities for
      asynchronous trajectory reading and parallel execution of analysis tasks by
      introducing analysis plugins which could be written in either C++ or Python in
      completely uniform way. The high level of abstraction provided by analysis
      plugins greatly simplifies prototyping and implementation of complex analysis
      algorithms. Pteros is available for free under Artistic License from
      http://sourceforge.net/projects/pteros/.

PMID- 25974374
TI  - Evaluation of gonorrhea test of cure at 1 week in a los angeles community-based
      clinic serving men who have sex with men: erratum.

PMID- 25974375
TI  - Bacterial Sexually Transmitted Infections Among HIV-Infected Patients in the
      United States: Estimates From the Medical Monitoring Project: Erratum.

PMID- 25974376
TI  - Correction: Accounting for Linear Transformations of EEG and MEG Data in Source
      Analysis.

PMID- 25974378
TI  - Knowledge, Attitudes, and Practice of Electronic Cigarette Use Among Pregnant
      Women.
AB  - OBJECTIVE: Electronic cigarettes (e-cigarettes) are a relatively recent
      phenomenon, serving dual roles as an alternative vehicle for nicotine delivery
      and a smoking-cessation tool. The purpose of this study was to determine pregnant
      women's knowledge, attitudes, and practice regarding electronic cigarettes. STUDY
      DESIGN: A voluntary, anonymous survey was distributed to a convenience sample of
      pregnant women presenting to a university-based outpatient clinic. After survey
      completion, participants received information about smoking cessation and e
      cigarettes. Data were examined using chi2 and Fisher exact tests and analysis of
      variance. Stata was used for the analysis. RESULTS: Of the 326 surveys
      distributed, 316 were completed (97%). Of the 316 participants, 42 (13%) reported
      having ever used e-cigarettes. Only 2 (0.6%) reported current daily use. Ever
      users were slightly older (27.3 years vs 25.4 years; P = 0.007) and more likely
      to be current smokers (43% vs. 14%; P < 0.001) compared with women who had never
      used electronic cigarettes. Knowledge of the harms of smoking was similar between
      the 2 groups. Overall, 57% of all respondents believed that e-cigarettes contain
      nicotine, 61% that e-cigarettes can be addictive, and 43% that e-cigarettes are
      less harmful to a fetus than traditional cigarettes. Among ever users, the most
      common reasons given for the use of e-cigarettes were the perception of less harm
      than traditional cigarettes (74%) and help with smoking cessation (72%).
      CONCLUSIONS: Misconceptions about e-cigarettes are common among pregnant women,
      potentially motivating use that may pose risks to both maternal and child health.
      Screening and education regarding e-cigarettes should be included in prenatal
      care. Future research in this area is necessary, including research examining
      pregnancy outcomes among women who use e-cigarettes.

PMID- 25974379
TI  - Tests of the Attachment and Clinical Issues Questionnaire as It Applies to
      Alcohol Dependence.
AB  - OBJECTIVES: Although many major theories tie the addictions to specific pathways
      and neurochemical systems evolutionarily implicated in food and social behavioral
      systems, there is a paucity of instruments from the psychological level that can
      measure these important attachment, social, and emotional counterparts. Two
      studies were designed to examine whether the Attachment and Clinical Issues
      Questionnaire (ACIQ) could help fill this limitation in psychological
      measurement. METHODS: In study 1, the ACIQ was given to patients in a substance
      abuse unit and control participants funneled to match from a larger population.
      To address the issue of their hypothesized tendency to blame everything on past
      experiences, study 2 tested whether the above results would be replicated with
      high school students predicted to develop alcohol dependence. RESULTS: In study
      1, on the patient population, significant differences were found on the
      attachment and clinical scales in predicted directions. In study 2, on the high
      school students, the central predictions were again confirmed with this different
      and larger population, but with interesting developmental differences.
      CONCLUSIONS: The 2 studies using different populations and definitions of alcohol
      dependence converged on similar results. The ACIQ was found to be a robust
      battery for measuring attachment and clinical issues displayed by both patient
      populations and high school students only predicted to develop alcohol
      dependence. The results were further discussed in terms of how they move us
      toward Research Domain Criteria (RDoC) approaches to diagnosis and treatment,
      paying attention to important individual differences in attachments, and clinical
      issues.

PMID- 25974377
TI  - Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus
      Vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Radiofrequency
      Catheter Ablation of Atrial Fibrillation: A Meta-Analysis.
AB  - BACKGROUND: Use of the non-vitamin K antagonist oral anticoagulants (NOACs) is
      endorsed by current guidelines for stroke prevention in patients with atrial
      fibrillation (AF). However efficacy and safety of NOACs in patients undergoing
      catheter ablation (RFCA) of AF has not been well established yet. OBJECTIVES: To
      perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist
      oral anticoagulants (VKAs) in patients undergoing RFCA. DATA SOURCES: Studies
      were searched for in PubMed and Google Scholar databases. STUDY ELIGIBILITY
      CRITERIA: Studies were considered eligible if: they evaluated the clinical impact
      of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during
      periprocedural phase of RFCA; they reported clinical outcome data. STUDY
      APPRAISAL AND SYNTHESIS METHODS: 25 studies were selected, including 9881 cases.
      The summary measure used was the risk ratio (RR) with 95% confidence interval
      (CI). The random-effects or the fixed effect model were used to synthesize
      results from the selected studies. RESULTS: There was no significant difference
      in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were
      significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67,
      p<0.001). Interestingly, a larger number of thromboembolic events was found in
      the VKAs-treated arm in those studies where VKAs had been interrupted during the
      periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly
      higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41;
      p=0.01) events was recorded. Conversely, the incidence of thromboembolic events
      in the VKAs-treated arm was significantly lower in those studies with
      uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).
      LIMITATIONS: As with every meta-analysis, no patients-level data were available.
      CONCLUSIONS AND IMPLICATIONS: The use of NOACs in patients undergoing RFCA is
      safe, given the lower incidence of bleedings observed with NOACs. On the other
      side, periprocedural interruption of VKAs and bridging with heparin is associated
      with a higher bleeding rate with no significant benefit on onset of
      thromboembolic events.

PMID- 25974380
TI  - Emergent Access to the Airway and Chest in American Football Players.
AB  - CONTEXT: American football has the highest rate of fatalities and catastrophic
      injuries of any US sport. The equipment designed to protect athletes from these
      catastrophic events challenges the ability of medical personnel to obtain neutral
      spine alignment and immobilization during airway and chest access for emergency
      life-support delivery. OBJECTIVE: To compare motion, time, and difficulty during
      removal of American football helmets, face masks, and shoulder pads. DESIGN:
      Quasi-experimental, crossover study. SETTING: Controlled laboratory. PATIENTS OR
      OTHER PARTICIPANTS: We recruited 40 athletic trainers (21 men, 19 women; age =
      33.7 +/- 11.2 years, height = 173.1 +/- 9.2 cm, mass = 80.7 +/- 17.1 kg,
      experience = 10.6 +/- 10.4 years). INTERVENTION(S): Paired participants conducted
      16 trials in random order for each of 4 helmet, face-mask, and shoulder-pad
      combinations. An 8-camera, 3-dimensional motion-capture system was used to record
      head motion in live models wearing properly fitted helmets and shoulder pads.
      MAIN OUTCOME MEASURE(S): Time and perceived difficulty (modified Borg CR-10).
      RESULTS: Helmet removal resulted in greater motion than face-mask removal,
      respectively, in the sagittal (14.88 degrees , 95% confidence interval [CI] =
      13.72 degrees , 16.04 degrees  versus 7.04 degrees , 95% CI = 6.20 degrees , 7.88
      degrees ; F(1,19) = 187.27, P < .001), frontal (7.00 degrees , 95% CI = 6.47
      degrees , 7.53 degrees  versus 4.73 degrees , 95% CI = 4.20 degrees , 5.27
      degrees ; F1,19 = 65.34, P < .001), and transverse (7.00 degrees , 95% CI = 6.49
      degrees , 7.50 degrees  versus 4.49 degrees , 95% CI = 4.07 degrees , 4.90
      degrees ; F(1,19) = 68.36, P < .001) planes. Face-mask removal from Riddell 360
      helmets took longer (31.22 seconds, 95% CI = 27.52, 34.91 seconds) than from
      Schutt ION 4D helmets (20.45 seconds, 95% CI = 18.77, 22.12 seconds) or complete
      ION 4D helmet removal (26.40 seconds, 95% CI = 23.46, 29.35 seconds). Athletic
      trainers required less time to remove the Riddell Power with RipKord (21.96
      seconds, 95% CI = 20.61 degrees , 23.31 degrees  seconds) than traditional
      shoulder pads (29.22 seconds, 95% CI = 27.27, 31.17 seconds; t(19) = 9.80, P <
      .001). CONCLUSIONS: Protective equipment worn by American football players must
      eventually be removed for imaging and medical treatment. Our results fill a gap
      in the evidence to support current recommendations for prehospital emergent
      management in patients wearing protective football equipment. Helmet face masks
      and shoulder pads with quick-release designs allow for clinically acceptable
      removal times without inducing additional motion or difficulty.

PMID- 25974381
TI  - Measuring Eccentric Strength of the Shoulder External Rotators Using a Handheld
      Dynamometer: Reliability and Validity.
AB  - CONTEXT: Shoulder strength assessment plays an important role in the clinical
      examination of the shoulder region. Eccentric strength measurements are of
      special importance in guiding the clinician in injury prevention or return-to
      play decisions after injury. OBJECTIVE: To examine the absolute and relative
      reliability and validity of a standardized eccentric strength-measurement
      protocol for the glenohumeral external rotators. DESIGN: Descriptive laboratory
      study. SETTING: Testing environment at the Department of Rehabilitation Sciences
      and Physiotherapy of Ghent University, Belgium. PATIENTS OR OTHER PARTICIPANTS:
      Twenty-five healthy participants (9 men and 16 women) without any history of
      shoulder pain were tested by 2 independent assessors using a handheld dynamometer
      (HHD) and underwent an isokinetic testing procedure. INTERVENTION(S): The
      clinical protocol used an HHD, a DynaPort accelerometer to measure acceleration
      and angular velocity of testing 30 degrees /s over 90 degrees  of range of
      motion, and a Biodex dynamometer to measure isokinetic activity. MAIN OUTCOME
      MEASURE(S): Three eccentric strength measurements: (1) tester 1 with the HHD, (2)
      tester 2 with the HHD, and (3) Biodex isokinetic strength measurement. RESULTS:
      The intratester reliability was excellent (0.879 and 0.858), whereas the
      intertester reliability was good, with an intraclass correlation coefficient
      between testers of 0.714. Pearson product moment correlation coefficients of 0.78
      and 0.70 were noted between the HHD and the isokinetic data, showing good
      validity of this new procedure. CONCLUSIONS: Standardized eccentric rotator cuff
      strength can be tested and measured in the clinical setting with good-to
      excellent reliability and validity using an HHD.

PMID- 25974382
TI  - A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly
      diagnosed patients with systemic immunoglobulin light chain amyloidosis.
AB  - Immunomodulatory drugs have been shown to be of benefit in relapsed/refractory
      immunoglobulin light-chain (AL) amyloidosis. We designed a prospective,
      multicentre phase II trial of lenalidomide, dexamethasone and cyclophosphamide
      for newly diagnosed patients with AL amyloidosis not eligible for autologous stem
      cell transplantation. Twenty-eight patients were included in the study. Cardiac
      involvement was present in 23 patients; 14 of them had cardiac stage III. The
      overall haematological response rate was 46%, including complete and very good
      partial responses in 25% and 18% of patients respectively. Haematological
      response was mainly associated with absence of cardiac stage III and lower tumour
      burden. Organ response was observed in 46% of patients. After a median follow-up
      of 24 months, median progression-free and overall survival have not been reached,
      both being significantly longer in responders (P < 0.001 and P = 0.001
      respectively). Seventeen patients have discontinued treatment, mostly due to
      amyloid-related death, disease progression or lack of response. Only 14% of the
      patients discontinued treatment due to therapy-related adverse events. Our
      results support the efficacy of this regimen, with high quality responses and
      prolonged survival, as well as its tolerability, in patients with AL amyloidosis
      not eligible for stem cell transplant and without advanced cardiac involvement
      (clinicaltrials.gov identifier: NCT01194791). 

PMID- 25974383
TI  - Manipulating Steady Heat Conduction by Sensu-shaped Thermal Metamaterials.
AB  - The ability to design the control of heat flow has innumerable benefits in the
      design of electronic systems such as thermoelectric energy harvesters, solid
      state lighting, and thermal imagers, where the thermal design plays a key role in
      performance and device reliability. In this work, we employ one identical sensu
      unit with facile natural composition to experimentally realize a new class of
      thermal metamaterials for controlling thermal conduction (e.g., thermal
      concentrator, focusing/resolving, uniform heating), only resorting to positioning
      and locating the same unit element of sensu-shape structure. The thermal
      metamaterial unit and the proper arrangement of multiple identical units are
      capable of transferring, redistributing and managing thermal energy in a
      versatile fashion. It is also shown that our sensu-shape unit elements can be
      used in manipulating dc currents without any change in the layout for the thermal
      counterpart. These could markedly enhance the capabilities in thermal sensing,
      thermal imaging, thermal-energy storage, thermal packaging, thermal therapy, and
      more domains beyond. 

PMID- 25974384
TI  - Prevention of gestational diabetes mellitus: Where are we now?
AB  - Gestational diabetes mellitus (GDM) is increasing at a rapid rate, driven by the
      increasing proportion of the population that is overweight/obese from a young
      age. More than 25 randomized controlled trials testing whether GDM can be
      prevented have now reported their findings, but only four different interventions
      have shown a reduction in the proportion of women with GDM (healthy eating alone,
      healthy eating with physical activity, myoinositol supplementation and probiotic
      treatment), and these results have not been replicated. The interventions tested
      to date include different diets and different forms of physical activity, in
      combination or alone, vitamin D, myoinositol, probiotics and metformin. Studies
      could be improved by using the International Association of Diabetes and
      Pregnancy Study Group criteria for GDM (which are probably more sensitive to
      change because of their multiple time points), targeting and tailoring
      interventions to subgroups most likely to benefit, and separating those with GDM
      early in pregnancy from those developing GDM de novo. The greatest societal
      benefit is likely to arise from population-based lifestyle approaches which
      include those women yet to become pregnant and those who are already pregnant and
      their families; an approach that is yet to be fully tested. 

PMID- 25974386
TI  - Cysteine-Functionalized Nanostructured Lipid Carriers for Oral Delivery of
      Docetaxel: A Permeability and Pharmacokinetic Study.
AB  - Here we report the development and evaluation of cysteine-modified nanostructured
      lipid carriers (NLCs) for oral delivery of docetaxel (DTX). The NLCs ensure high
      encapsulation efficiency of docetaxel, while the cysteine bound the NLCs with
      PEG2000-monostearate (PEG2000-MSA) as a linker, and allowed a specific
      interaction with mucin of the intestinal mucus layer and facilitated the
      intestinal transport of docetaxel. The cysteine-modified NLCs (cNLCs) had a small
      particle size (<100 nm) and a negative zeta potential (-13.72 +/- 0.07 mV), which
      was lower than that of the unmodified NLCs (uNLCs) (-6.39 +/- 0.07 mV). This
      correlates well with the location of the cysteine group on the surface of the
      NLCs obtained by X-ray photoelectron spectroscopy (XPS). The cNLCs significantly
      improved the mucoadhesion properties compared with uNLCs. The intestinal
      absorption of cNLCs in total intestinal segments was greatly improved in
      comparison with uNLCs and docetaxel solution (DTX-Sol), and the in vivo imaging
      system captured pictures also showed not only increased intestinal absorption but
      also improved accumulation in blood. The cNLCs could be absorbed into the
      enterocytes via both endocytosis and passive transport. The results of the in
      vivo pharmacokinetic study indicated that the AUC0-t of cNLCs (1533.00 ng/mL.h)
      was markedly increased 12.3-fold, and 1.64-fold compared with docetaxel solution
      and uNLCs, respectively. Overall, the cysteine modification makes nanostructured
      lipid carriers more suitable as nanocarriers for oral delivery of docetaxel. 

PMID- 25974387
TI  - Does bad inference drive out good?
AB  - The (mis)use of statistics in practice is widely debated, and a field where the
      debate is particularly active is medicine. Many scholars emphasize that a large
      proportion of published medical research contains statistical errors. It has been
      noted that top class journals like Nature Medicine and The New England Journal of
      Medicine publish a considerable proportion of papers that contain statistical
      errors and poorly document the application of statistical methods. This paper
      joins the debate on the (mis)use of statistics in the medical literature. Even
      though the validation process of a statistical result may be quite elusive, a
      careful assessment of underlying assumptions is central in medicine as well as in
      other fields where a statistical method is applied. Unfortunately, a careful
      assessment of underlying assumptions is missing in many papers, including those
      published in top class journals. In this paper, it is shown that nonparametric
      methods are good alternatives to parametric methods when the assumptions for the
      latter ones are not satisfied. A key point to solve the problem of the misuse of
      statistics in the medical literature is that all journals have their own
      statisticians to review the statistical method/analysis section in each submitted
      paper. 

PMID- 25974388
TI  - Metal-based nanotoxicity and detoxification pathways in higher plants.
AB  - The potential risks from metal-based nanoparticles (NPs) in the environment have
      increased with the rapidly rising demand for and use of nanoenabled consumer
      products. Plant's central roles in ecosystem function and food chain integrity
      ensure intimate contact with water and soil systems, both of which are considered
      sinks for NPs accumulation. In this review, we document phytotoxicity caused by
      metal-based NPs exposure at physiological, biochemical, and molecular levels.
      Although the exact mechanisms of plant defense against nanotoxicity are unclear,
      several relevant studies have been recently published. Possible detoxification
      pathways that might enable plant resistance to oxidative stress and facilitate
      NPs detoxification are reviewed herein. Given the importance of understanding the
      effects and implications of metal-based NPs on plants, future research should
      focus on the following: (1) addressing key knowledge gaps in understanding
      molecular and biochemical responses of plants to NPs stress through global
      transcriptome, proteome, and metablome assays; (2) designing long-term
      experiments under field conditions at realistic exposure concentrations to
      investigate the impact of metal-based NPs on edible crops and the resulting
      implications to the food chain and to human health; and (3) establishing an
      impact assessment to evaluate the effects of metal-based NPs on plants with
      regard to ecosystem structure and function.

PMID- 25974385
TI  - Metallothionein as a clonable tag for protein localization by electron microscopy
      of cells.
AB  - A benign, clonable tag for the localization of proteins by electron microscopy of
      cells would be valuable, especially if it provided labelling with high signal-to
      noise ratio and good spatial resolution. Here we explore the use of
      metallothionein as such a localization marker. We have achieved good success with
      desmin labelled in vitro and with a component of the yeast spindle pole body
      labelled in cells. Heavy metals added after fixation and embedding or during the
      process of freeze-substitution fixation provide readily visible signals with no
      concern that the heavy atoms are affecting the behaviour of the protein in its
      physiological environment. However, our methods did not work with protein
      components of the nuclear pore complex, suggesting that this approach is not yet
      universally applicable. We provide a full description of our optimal labelling
      conditions and other conditions tried, hoping that our work will allow others to
      label their own proteins of interest and/or improve on the methods we have
      defined. 

PMID- 25974389
TI  - Association between cannabinoid receptor type 2 Q63R variant and
      oligo/polyarticular juvenile idiopathic arthritis.
AB  - OBJECTIVES: To investigate whether the functional variant Q63R of the cannabinoid
      2 (CB2) receptor is associated with susceptibility to oligo/poly-articular
      juvenile idiopathic arthritis (JIA) and with its clinical features. METHOD: A
      total of 171 Italian children with oligoarticular/rheumatoid factor negative poly
      articular JIA and 600 healthy controls were enrolled in the study and genotyped.
      RESULTS: A significant difference in genotype distribution of the CB2 Q63R
      variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls
      was found (p = 0.001). The R63 variant was associated with increased rates of
      relapse (p = 0.0001). CONCLUSIONS: This study indicates that the CB2 receptor
      contributes to susceptibility to oligo/polyarticular JIA and to the severity of
      its clinical course.

PMID- 25974390
TI  - Heterogeneous H-bonding in a foldamer helix.
AB  - Structural characterization of new alpha/gamma-peptide foldamers containing the
      cyclically constrained gamma-amino acid I is described. Crystallographic and 2D
      NMR analysis shows that gamma residue I promotes the formation of a 12/10-helical
      secondary structure in alpha/gamma-peptides. This helix contains two different
      types of internal H-bond, and the data show that the 12-atom C?O(i) -> H-N(i+3) H
      bond is more favorable than the 10-atom C?O(i) -> H-N(i-1) H-bond. Several
      foldamer helices featuring topologically distinct H-bonds have been discovered,
      but our findings are the first to show that such H-bonds may differ in their
      favorability. 

PMID- 25974391
TI  - Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and
      BRPF.
AB  - TRIM24 is a transcriptional regulator as well as an E3 ubiquitin ligase. It is
      overexpressed in diverse tumors, and high expression levels have been linked to
      poor prognosis in breast cancer patients. TRIM24 contains a PHD/bromodomain
      offering the opportunity to develop protein interaction inhibitors that target
      this protein interaction module. Here we identified potent acetyl-lysine mimetic
      benzimidazolones TRIM24 bromodomain inhibitors. The best compound of this series
      is a selective BRPF1B/TRIM24 dual inhibitor that bound with a KD of 137 and 222
      nM, respectively, but exerted good selectivity over other bromodomains. Cellular
      activity of the inhibitor was demonstrated using FRAP assays as well as cell
      viability data. 

PMID- 25974393
TI  - A Proof-of-Principle Setup for Delivery of Relenza(r) (Zanamivir) Inhalation
      Powder to Intubated Patients.
AB  - BACKGROUND: A fatal incident was reported when a mechanical ventilated patient
      received nebulization of a reconstituted Relenza(r) formulation. We propose a
      delivery system to introduce Relenza and other inhalation dry powders to
      intubated patients to avoid accidental fatalities in the future. METHODS: This is
      a bench study demonstrating the feasibility of a delivery system to introduce dry
      powder of Relenza to intubated patients. A dry powder inhaler placed within a
      delivery chamber was actuated by compressing a ventilation bag to disperse powder
      into a tracheal tube. The performance of two inhalers, a Diskhaler(r) and an
      OsmohalerTM, were compared. The effects of the length and size of the tracheal
      tube on the powder output and sizing of emitted powder were investigated using
      the more efficient OsmohalerTM. RESULTS: The efficiency of Osmohaler in
      delivering Relenza to the distal end [delivered dose=30.2+/-0.2% and fine
      particle fraction (FPF)=14.5+/-1.7%] was significantly higher than the Diskhaler
      (delivered dose=18.1+/-4.7% and FPF=3.4+/-2.1%). While no differences in the
      delivered dose and FPF were observed between the tracheostomy and endotracheal
      tubes of the same internal diameter, a larger endotracheal tube (9.0 mm internal
      diameter) gave a 6% higher FPF compared with the smaller counterpart (7.0 mm
      internal diameter). CONCLUSION: The dry powder delivery system has been
      demonstrated to be capable of delivering Relenza formulation to the distal end of
      tracheal tubes with a reasonable delivered dose and FPF. It would be necessary
      for further investigation into incorporating the proposed powder delivery system
      within a mechanical ventilator, as well as animal and clinical studies to prove
      its applicability to deliver zanamivir dry powder to ventilated influenza
      patients in the intensive care setting.

PMID- 25974392
TI  - Aging affects sex categorization of male and female faces in opposite ways.
AB  - Faces are rich in social information; they easily give away a person's sex,
      approximate age, feelings, or focus of attention. Past research has mostly
      focused on investigating the distinct facial signals and perceptual mechanisms
      that allow us to categorize faces on these individual dimensions. It is less well
      understood how the different kinds of facial information interact. Here we
      investigated how the age of a face affects the ease with which young and older
      adults categorize its sex. Disconfirming everyday intuition, we showed that sex
      categorization is not generally hampered for older faces. Although categorization
      of female faces took progressively more time with increasing age, the opposite
      was found for male faces (Experiment 1). Differential effects of stimulus
      blurring and inversion for male and female faces of different ages (Experiment 2)
      strongly suggest one feature as a crucial mediator of the interdependence of age
      and sex perception - skin texture. 

PMID- 25974395
TI  - Differences in the Expression of Cold Stress-Related Genes and in the Swarming
      Motility Among Persistent and Sporadic Strains of Listeria monocytogenes.
AB  - The persistence of certain Listeria monocytogenes strains in food-related
      environments suggests niche adaptation of these strains and therefore constitutes
      a major risk to consumer health and results in economic losses for the food
      producer. In this study, a set of 23 L. monocytogenes isolates, including a group
      of persistent and a group of sporadic strains, was evaluated regarding their
      swarming motility at 11 degrees C. In each group, significant (p<0.05)
      differences in motility were observed. The transcript levels of nine cold stress
      related genes were analyzed by real-time quantitative PCR in two representatives
      of persistent (CBISA3077) and sporadic (CBISA3049) strains isolated from the
      dairy environment, and significant (p<0.05) differences between the two strains
      were observed. The persistent strain showed significantly higher transcript
      levels of dtpT and sigB genes, and significantly lower levels of flaA, oppA,
      lmo1722, and lmo0866 genes. In the persistent strain, the upregulation of sigB,
      involved in the tolerance to low temperature and to osmotic stress, could account
      for the persistence of this strain in its original dairy environment. In a
      similar way, the downregulation of two helicase-encoding genes lmo1722 and
      lmo0866, in this strain, may be an evolutionary trait that could facilitate cold
      stress adaptation. Even though this analysis should be extended to more sporadic
      and more persistent strains, the results presented here strongly suggest gene
      expression networks differently adjusted, in the two strains, to the low
      temperature environment from where they were collected. Moreover, our findings
      suggest that bacterial motility per se should not be considered a key feature for
      the persistence of L. monocytogenes in the food environment. 

PMID- 25974394
TI  - Trichostatin A specifically improves the aberrant expression of transcription
      factor genes in embryos produced by somatic cell nuclear transfer.
AB  - Although mammalian cloning by somatic cell nuclear transfer (SCNT) has been
      established in various species, the low developmental efficiency has hampered its
      practical applications. Treatment of SCNT-derived embryos with histone
      deacetylase (HDAC) inhibitors can improve their development, but the underlying
      mechanism is still unclear. To address this question, we analysed gene expression
      profiles of SCNT-derived 2-cell mouse embryos treated with trichostatin A (TSA),
      a potent HDAC inhibitor that is best used for mouse cloning. Unexpectedly, TSA
      had no effect on the numbers of aberrantly expressed genes or the overall gene
      expression pattern in the embryos. However, in-depth investigation by gene
      ontology and functional analyses revealed that TSA treatment specifically
      improved the expression of a small subset of genes encoding transcription factors
      and their regulatory factors, suggesting their positive involvement in de novo
      RNA synthesis. Indeed, introduction of one of such transcription factors, Spi-C,
      into the embryos at least partially mimicked the TSA-induced improvement in
      embryonic development by activating gene networks associated with transcriptional
      regulation. Thus, the effects of TSA treatment on embryonic gene expression did
      not seem to be stochastic, but more specific than expected, targeting genes that
      direct development and trigger zygotic genome activation at the 2-cell stage. 

PMID- 25974396
TI  - Tumor Necrosis Factor Related Apoptosis Inducing Ligand (Trail) in endothelial
      response to biomechanical and biochemical stresses in arteries.
AB  - Shear stress is determined by three physical components described in a famous
      triad: blood flow, blood viscosity and vessel geometry. Through the direct action
      on endothelium, shear stress is able to radically interfere with endothelial
      properties and the physiology of the vascular wall. Endothelial cells (ECs) have
      also to sustain biochemical stresses represented by chemokines, growth factors,
      cytokines, complement, hormones, nitric oxide (NO), oxygen and reactive oxygen
      species (ROS). Many growth factors, cytokines, chemokines, hormones, and chemical
      substances, like NO, act and regulate endothelium functions and homeostasis.
      Among these cytokines Tumor Necrosis Factor Related Apoptosis Inducing Ligand
      (TRAIL) has been assigned a regulatory role in ECs physiology and
      physiopathology. Thus, the aim of this review is to provide a general overview of
      the endothelial response pathways after different types of biomechanical and
      biochemical stress in in vitro models and to analyze the crucial role of TRAIL
      under pathological conditions of the cardiocirculatory system like
      atherosclerosis, coronary artery disease, and diabetes.

PMID- 25974397
TI  - Sphenoid wing meningiomas: Surgical strategies and evaluation of prognostic
      factors influencing clinical outcomes.
AB  - OBJECTIVE: To study microsurgical technique and prognostic factors influencing
      clinical outcomes in a series of 53 patients with sphenoid wing meningiomas
      (SWMs). MATERIALS AND METHODS: The clinical materials of 53 patients with
      sphenoid wing meningiomas treated microsurgically between January 2008 and
      January 2012 were analyzed retrospectively. Follow-up period ranged from 6 to 62
      months (median, 34 months). Clinical outcomes including postoperative quality of
      life and recurrence rate were evaluated. Univariate and multivariate statistical
      analysis were performed among factors that might influence postoperative quality
      of life. RESULTS: In our group, the mean age of patients was 49 years. Mean tumor
      size was 3.9cm. Total tumor resection was achieved in 38 cases (71.7%), subtotal
      in 10 cases (18.9%) and partial resection in 5 cases (9.4%). Within the follow-up
      period, ten patients (18.9%) had recurrence and three patients (5.7%) died. In
      univariate analysis, we found the postoperative Karnofshky Performance Score
      (KPS) improvement was determined by various factors, including extent of tumor
      resection, peritumoral edema, tumor blood supply, size, adhesion, encasement and
      preoperative KPS. However, multivariate analysis showed that complete resection,
      rich blood supply, adhesion to adjacent structure, encasement of neurovascular
      were independent predictive factors for worse postoperative KPS. CONCLUSIONS:
      With the improved requirement of postoperative quality of life in patients,
      intentional incomplete resection should be considered as an acceptable treatment
      option. Multivariate analysis confirmed that incomplete resection, poor blood
      supply, lack of adhesion or encasement of adjacent structure were independent
      predictive factors for favorable postoperative quality of life. An individual
      treatment strategy could help improved quality of life.

PMID- 25974398
TI  - The endonasal approach for treatment of cerebral aneurysms: A critical review of
      the literature.
AB  - The last two decades of neurosurgery have seen flourishing use of the endonasal
      approach for the treatment of skull base tumors. Safe and effective resections of
      neoplasms requiring intracranial arterial dissection have been performed using
      this technique. Recently, there have been a growing number of case reports
      describing the use of the endonasal approach to surgically clip cerebral
      aneurysms. We review the use of these approaches in intracranial aneurysm
      clipping and analyze its advantages, limitations, and consider future directions.
      Three major electronic databases were queried using relevant search terms.
      Pertinent case studies of unruptured and ruptured aneurysms were considered. Data
      from included studies were analyzed. 8 case studies describing 9 aneurysms (4
      ruptured and 5 unruptured) treated by the endonasal approach met inclusion
      criteria. All studies note the ability to gain proximal and distal control and
      successful aneurysm obliteration was obtained for 8 of 9 aneurysms. 1
      intraoperative rupture occurred and was controlled, and delayed complications of
      cerebrospinal fluid leak, vasospasm, and hydrocephalus occurred in 1, 1, and 2
      patients, respectively. Described limitations of this technique include aneurysm
      orientation and location, the need for lower profile technology, and challenges
      with handling intraoperative rupture. The endonasal approach for clipping of
      intracranial aneurysms can be an effective approach in only very select cases as
      demonstrated clinically and through cadaveric exploration. Further investigation
      with lower profile clip technology and additional studies need to be performed.
      Options of alternative therapy, limitations of this approach, and team experience
      must first be considered. 

PMID- 25974399
TI  - Induction of the pi class of glutathione S-transferase by carnosic acid in rat
      Clone 9 cells via the p38/Nrf2 pathway.
AB  - Induction of phase II enzymes is important in cancer chemoprevention. We compared
      the effect of rosemary diterpenes on the expression of the pi class of
      glutathione S-transferase (GSTP) in rat liver Clone 9 cells and the signaling
      pathways involved. Culturing cells with 1, 5, 10, or 20 MUM carnosic acid (CA) or
      carnosol (CS) for 24 h in a dose-dependent manner increased the GSTP expression.
      CA was more potent than CS. The RNA level and the enzyme activity of GSTP were
      also enhanced by CA treatment. Treatment with 10 MUM CA highly induced the
      reporter activity of the enhancer element GPEI. Furthermore, CA markedly
      increased the translocation of nuclear factor erythroid-2 related factor 2 (Nrf2)
      from the cytosol to the nucleus after 30 to 60 min. CA the stimulated the protein
      induction of p38, nuclear Nrf2, and GSTP was diminished in the presence of
      SB203580 (a p38 inhibitor). In addition, SB203580 pretreatment or silencing of
      Nrf2 by siRNA suppressed the CA-induced GPEI-DNA binding activity and GSTP
      protein expression. Knockdown of p38 or Nrf2 by siRNA abolished the activation of
      p38 and Nrf2 as well as the protein induction and enzyme activity of GSTP by CA.
      These results suggest that CA up-regulates the expression and enzyme activity of
      GSTP via the p38/Nrf2/GPEI pathway.

PMID- 25974400
TI  - Correction: dynamic endothelial cell rearrangements drive developmental vessel
      regression.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.1002125.]. 

PMID- 25974401
TI  - Two Zebrafish hsd3b Genes Are Distinct in Function, Expression, and Evolution.
AB  - HSD3B catalyzes the synthesis of delta4 steroids such as progesterone in the
      adrenals and gonads. Individuals lacking HSD3B2 activity experience congenital
      adrenal hyperplasia with imbalanced steroid synthesis. To develop a zebrafish
      model of HSD3B deficiency, we characterized 2 zebrafish hsd3b genes. Our
      phylogenetic and conserved synteny analyses showed that the tandemly duplicated
      human HSD3B1 and HSD3B2 genes are coorthologs of zebrafish hsd3b1 on chromosome 9
      (Dre9), whereas the gene called hsd3b2 resides on Dre20 in an ancestral
      chromosome segment, from which its ortholog was lost in the tetrapod lineage.
      Zebrafish hsd3b1(Dre 9) was expressed in adult gonads and headkidney, which
      contains interrenal glands, the zebrafish counterpart of the tetrapod adrenal.
      Knockdown of hsd3b1(Dre 9) caused the interrenal and anterior pituitary to expand
      and pigmentation to increase, resembling human HSD3B2 deficiency. The zebrafish
      hsd3b2(Dre 20) gene was expressed in zebrafish early embryos as maternal
      transcripts that disappeared 1 day after fertilization. Morpholino inactivation
      of hsd3b2(Dre 20) led to embryo elongation, which was rescued by the injection of
      hsd3b2 mRNA. Thus, zebrafish hsd3b2(Dre 20) evolved independently of hsd3b1(Dre
      9) with a morphogenetic function during early embryogenesis. Zebrafish hsd3b1(Dre
      9), on the contrary, functions like mammalian HSD3B2, whose deficiency leads to
      congenital adrenal hyperplasia. 

PMID- 25974402
TI  - Identification and Characterization of the Androgen Receptor From the American
      Alligator, Alligator mississippiensis.
AB  - Androgens are essential for the development, reproduction, and health throughout
      the life span of vertebrates, particularly during the initiation and maintenance
      of male sexual characteristics. Androgen signaling is mediated by the androgen
      receptor (AR), a member of the steroid nuclear receptor superfamily. Mounting
      evidence suggests that environmental factors, such as exogenous hormones or
      contaminants that mimic hormones, can disrupt endocrine signaling and function.
      The American alligator (Alligator mississippiensis), a unique model for
      ecological research in that it exhibits environment-dependent sex determination,
      is oviparous and long lived. Alligators from a contaminated environment exhibit
      low reproductive success and morphological disorders of the testis and phallus in
      neonates and juveniles, both associated with androgen signaling; thus, the
      alterations are hypothesized to be related to disrupted androgen signaling.
      However, this line of research has been limited because of a lack of information
      on the alligator AR gene. Here, we isolated A mississippiensis AR homologs (AmAR)
      and evaluated receptor-hormone/chemical interactions using a transactivation
      assay. We showed that AmAR responded to all natural androgens and their effects
      were inhibited by cotreatment with antiandrogens, such as flutamide, p,p'
      dichlorodiphenyldichloroethylene, and vinclozolin. Intriguingly, we found a
      spliced form of the AR from alligator cDNA, which lacks seven amino acids within
      the ligand-binding domain that shows no response to androgens. Finally, we have
      initial data on a possible dominant-negative function of the spliced form of the
      AR against androgen-induced AmAR. 

PMID- 25974404
TI  - Clinical significance and prognostic impact of the total diameter of enlarged
      lymph nodes on preoperative multidetector computed tomography in patients with
      gastric cancer.
AB  - BACKGROUND AND AIM: This study was designed to evaluate the clinical significance
      and prognostic impact of the total diameter of enlarged lymph nodes (TDL) on
      preoperative multidetector computed tomography (MDCT) in gastric cancer (GC).
      METHODS: Of a total of 480 GC patients between 2005 and 2009, 70 patients with a
      preoperative diagnosis of nodal metastasis on MDCT were included in this study.
      All regional lymph nodes showing metastatic involvement were preoperatively
      counted and measured. RESULTS: The TDL was calculated, and using a receiver
      operating characteristic curve, a cutoff value of 45 mm in the two groups of
      large TDL (LTDL) and small TDL was found to be appropriate for TDL. No
      significant differences were observed in clinicopathological features, except for
      tumor recurrence, between the two groups. Univariate survival analysis revealed
      that patients with LTDL had a worse prognosis as well as an upper tumor location,
      deeper tumor depth, and further advanced pathological stage. Multivariable
      prognostic analysis identified LTDL as an independent worse prognostic factor (P
      = 0.0128). CONCLUSIONS: GC patients with the total nodal diameter measuring 45 mm
      or more on MDCT have a worse prognosis. GC patients with the novel surrogate
      indicator of worse prognosis for a preoperative imaging diagnosis may have need
      of multimodal treatment to improve the survival.

PMID- 25974403
TI  - 5alpha-Reductase Type 2 Regulates Glucocorticoid Action and Metabolic Phenotype
      in Human Hepatocytes.
AB  - Glucocorticoids and androgens have both been implicated in the pathogenesis of
      nonalcoholic fatty liver disease (NAFLD); androgen deficiency in males, androgen
      excess in females, and glucocorticoid excess in both sexes are associated with
      NAFLD. Glucocorticoid and androgen action are regulated at a prereceptor level by
      the enzyme 5alpha-reductase type 2 (SRD5A2), which inactivates glucocorticoids to
      their dihydrometabolites and converts T to DHT. We have therefore explored the
      role of androgens and glucocorticoids and their metabolism by SRD5A2 upon lipid
      homeostasis in human hepatocytes. In both primary human hepatocytes and human
      hepatoma cell lines, glucocorticoids decreased de novo lipogenesis in a dose
      dependent manner. Whereas androgen treatment (T and DHT) increased lipogenesis in
      cell lines and in primary cultures of human hepatocytes from female donors, it
      was without effect in primary hepatocyte cultures from men. SRD5A2 overexpression
      reduced the effects of cortisol to suppress lipogenesis and this effect was lost
      following transfection with an inactive mutant construct. Conversely,
      pharmacological inhibition using the 5alpha-reductase inhibitors finasteride and
      dutasteride augmented cortisol action. We have demonstrated that manipulation of
      SRD5A2 activity can regulate lipogenesis in human hepatocytes in vitro. This may
      have significant clinical implications for those patients prescribed 5alpha
      reductase inhibitors, in particular augmenting the actions of glucocorticoids to
      modulate hepatic lipid flux. 

PMID- 25974405
TI  - A comparative study of adaptive dose-finding designs for phase I oncology trials
      of combination therapies.
AB  - Little is known about the relative performance of competing model-based dose
      finding methods for combination phase I trials. In this study, we focused on five
      model-based dose-finding methods that have been recently developed. We compared
      the recommendation rates for true maximum-tolerated dose combinations (MTDCs) and
      over-dose combinations among these methods under 16 scenarios for 3 * 3, 4 * 4, 2
      * 4, and 3 * 5 dose combination matrices. We found that performance of the model
      based dose-finding methods varied depending on (1) whether the dose combination
      matrix is square or not; (2) whether the true MTDCs exist within the same group
      along the diagonals of the dose combination matrix; and (3) the number of true
      MTDCs. We discuss the details of the operating characteristics and the advantages
      and disadvantages of the five methods compared.

PMID- 25974406
TI  - Effectiveness and Reliability of Selected Site Pacing for Avoidance of Phrenic
      Nerve Stimulation in CRT Patients with Quadripolar LV Leads: The EffaceQ Study.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) relies on sufficient left
      ventricular (LV) pacing with safety margin to phrenic nerve stimulation (PNS).
      Previous studies introduced LV vector reprogramming in bipolar coronary sinus
      leads to optimize LV pacing and avoid PNS. We investigated the efficacy and
      reliability of quadripolar leads in CRT. METHODS: The EffaceQ study enrolled 344
      patients with de novo CRT implantation with a quadripolar LV lead in an
      observational, prospective multicenter study. The study was powered to
      demonstrate that in at least 90% of patients with an implanted quadripolar LV
      lead, a viable LV pacing configuration (LVPC) is available (primary end point: LV
      pacing threshold <=2.5 V/0.5 ms, sufficient PNS margin). RESULTS: Quadripolar
      leads were successfully implanted in 96% of patients. A total of 278 of 299
      (93.0%) patients with complete data met the criteria for viable LVPC. With the
      use of traditional LVPCs, a viable LVPC would have been available (268 of 299
      patients; P = 0.002) in significantly fewer patients (89.6%). In any LVPC, PNS
      was inducible in 65.0% of patients and 22.6% of patients reported PNS during
      ambulatory 3-month follow-up. LVPC reprogramming was performed in 49.8% of
      patients. PNS inducibility decreased from distal to proximal electrodes, whereas
      LV pacing thresholds increased from distal to proximal. At prehospital discharge,
      5.9 +/- 2.8 viable LVPCs were observed, stable during follow-up. The quadripolar
      electrode offered significantly more LVPC for LV optimization and PNS avoidance.
      CONCLUSION: Quadripolar LV leads yield high numbers of patients with viable LVPCs
      and alternatives for noninvasive repositioning of LV pacing.

PMID- 25974408
TI  - Estimating Geriatric Mortality after Injury Using Age, Injury Severity, and
      Performance of a Transfusion: The Geriatric Trauma Outcome Score.
AB  - BACKGROUND: A tool to determine the probability of mortality for severely injured
      geriatric patients is needed. OBJECTIVE: We sought to create an easily calculated
      geriatric trauma prognostic score based on parameters available at the bedside to
      aid in mortality probability determination. METHODS: All patients >= 65 years of
      age were identified from our Level I trauma center's registry between January 1,
      2000 and December 31, 2013. Measurements included age, Injury Severity score
      (ISS), units of packed red blood cells (PRBCs) transfused in the first 24 hours,
      and patients' mortality status at the end of their index hospitalization. As a
      first step, a logistic regression model with maximum likelihood estimation and
      robust standard errors was used to estimate the odds of mortality from age, ISS,
      and PRBCs after dichotomizing PRBCs as yes/no. We then constructed a Geriatric
      Trauma Outcome (GTO) score that became the sole predictor in the re-specified
      logistic regression model. RESULTS: The sample (n = 3841) mean age was 76.5 +/-
      8.1 years and the mean ISS was 12.4 +/- 9.8. In-hospital mortality was 10.8%, and
      11.9% received a transfusion by 24 hours. Based on the logistic regression model,
      the equation with the highest discriminatory ability to estimate probability of
      mortality was GTO Score = age + (2.5 * ISS) + 22 (if given PRBCs). The area under
      the receiver operating characteristic curve (AUC) for this model was 0.82.
      Selected GTO scores and their related probability of dying were: 205 = 75%, 233 =
      90%, 252 = 95%, 310 = 99%. The range of GTO scores was 67.5 (survivor) to 275.1
      (died). CONCLUSION: The GTO model accurately estimates the probability of dying,
      and can be calculated at bedside by those possessing a working knowledge of ISS
      calculation.

PMID- 25974409
TI  - Public Health Management, Climate Change, and Incarceration: What Is the
      Connection?

PMID- 25974407
TI  - Disproportionate fetal growth and the risk for congenital cerebral palsy in
      singleton births.
AB  - OBJECTIVE: To investigate the association between proportionality of fetal and
      placental growth measured at birth and the risk for congenital cerebral palsy
      (CP). STUDY DESIGN: We identified all live-born singletons born in Denmark
      between 1995 and 2003 and followed them from 1 year of age until December 31st,
      2008. Information on four indices of fetal growth: ponderal index, head
      circumference/ abdominal circumference ratio, cephalization index and birth
      weight/ placenta weight ratio was collected. Cox proportional hazards regression
      models were used to estimate adjusted hazard ratios (aHR) and 95% confidence
      intervals (CI). All measurements were evaluated as gestational age and sex
      specific z-scores and in z-score percentile groups, adjusted for potential
      confounders, and stratified on gestational age groups (<32, 32-36, 37-38, 39, 40,
      >= 41 weeks). RESULTS: We identified 503,784 singleton births, of which 983 were
      confirmed cases of CP. Head/ abdominal circumference ratio (aHR:1.12; 95%CI:1.07
      1.16) and cephalization index (aHR:1.14; 95%CI:1.11-1.16) were associated with
      the risk of CP irrespective of gestational age. Birth weight-placental weight
      ratio was also associated with CP in the entire cohort (aHR:0.90; 95%CI:0.83
      0.97). Ponderal index had a u-shaped association with CP, where both children
      with low and high ponderal index were at higher risk of CP. CONCLUSIONS: CP is
      associated with disproportions between birth weight, birth length, placental
      weight and head circumference suggesting pre and perinatal conditions contribute
      to fetal growth restriction in children with CP.

PMID- 25974410
TI  - The Effect of Pseudoexfoliation and Pseudoexfoliation Induced Dry Eye on Central
      Corneal Thickness.
AB  - PURPOSE/AIM OF THE STUDY: The aim of this study is to investigate the effect of
      pseudoexfoliation (PEX) and PEX-induced dry eye on central corneal thickness
      (CCT). MATERIALS AND METHODS: This cross-sectional study consists of total 270
      eyes of 135 patients (67 females, 68 males) in total. After excluding the PEX (-)
      32 eyes with PEX in the other eye, totally 130 eyes in PEX (-) group and 108 eyes
      in the PEX (+) group were included in the study. The PEX (+) group was regrouped
      as PEX syndrome (80 eyes of 50 patients) and PEX glaucoma (28 eyes of 20
      patients). RESULTS: In the PEX (-) group, the mean Schirmer test result was 12 +/
      4 mm (4-25 mm), in the PEX syndrome group 10 +/- 4 mm (4-22 mm), in the PEX
      glaucoma group 9 +/- 3 mm (4-15 mm). The difference among the PEX (-) group, the
      PEX syndrome and the PEX glaucoma groups was statistically significant (p <
      0.001, p < 0.001, respectively). In the PEX (-) group, the mean tear break up
      time test result was 11 +/- 2 s (5-16 s), in the PEX syndrome group 8 +/- 3 (3-16
      s), in the PEX glaucoma group 8 +/- 3 s (5-15 s). Mean CCT result was 544 um in
      the PEX (-), 521 um in the PEX syndrome group and 533 um in the PEX glaucoma
      group. The difference among the PEX (-) group, the PEX syndrome and the PEX
      glaucoma groups was significant (p < 0.001, p = 0.030, respectively). There was a
      significant (+) correlation between intraocular pressure and CCT in the eyes with
      PEX (r = 0.307, p = 0.001). However, there was no statistically significant
      correlation between CCT, Schirmer and tear break up time tests in the eyes with
      PEX. CONCLUSIONS: PEX material can cause decrease in tear film secretion and
      disturb tear film stability. There is no effect of PEX-induced dry eye on CCT.
      Lower CCT values in the eyes with PEX material may be a result of decrease in
      corneal stromal cell density. Moreover, higher CCT values may be because of
      decreased endothelial cells in PEX glaucoma patients.

PMID- 25974412
TI  - 25th Anniversary State-of-the-Art Expert Discussion With George W. Holcomb, MD,
      on the Evolution of Minimally Invasive Surgery Techniques with a Close-Up on
      Laparoscopic Fundoplication.

PMID- 25974411
TI  - Non-random distribution of macromolecules as driving forces for phenotypic
      variation.
AB  - Clonal populations employ many strategies of diversification to deal with
      constraints. All these strategies result in the generation of different
      phenotypes with diverse functions. Events like cell division are major sources of
      phenotypic variability due to the unequal partitioning of cellular components. In
      this review we concentrate on passive and active mechanisms cells employ to
      distribute macromolecules between their offspring. Different types of segregation
      are described, addressing both metabolically pertinent molecules such as PHA/PHB
      or polyphosphates, and components that adversely affect cells by promoting aging,
      such as damaged protein complexes or extrachromosomal rDNA circles. We also refer
      to mechanisms generating plasmid copy number (PCN) variation between cells in a
      population, and how elaborate partitioning systems counteract partitioning errors
      and ensure equal distribution. Finally, we demonstrate how simple differences in
      chromosomal copy number determine the fate of a cell, in this case the effect of
      gene dosage on the onset of sporulation in Bacillus subtilis or on a functional
      trait in Sinorhizobium meliloti. 

PMID- 25974413
TI  - A Social Network Analysis of 140 Community-Academic Partnerships for Health:
      Examining the Healthier Wisconsin Partnership Program.
AB  - INTRODUCTION: Social Network Analysis (SNA) provides an important, underutilized
      approach to evaluating Community Academic Partnerships for Health (CAPHs). This
      study examines administrative data from 140 CAPHs funded by the Healthier
      Wisconsin Partnership Program (HWPP). METHODS: Funder data was normalized to
      maximize number of interconnections between funded projects and 318 non-redundant
      community partner organizations in a dual mode analysis, examining the period
      from 2003-2013.Two strategic planning periods, 2003-2008 vs. 2009-2014, allowed
      temporal comparison. RESULTS: Connectivity of the network was largely unchanged
      over time, with most projects and partner organizations connected to a single
      large component in both time periods. Inter-partner ties formed in HWPP projects
      were transient. Most community partners were only involved in projects during one
      strategic time period. Community organizations participating in both time periods
      were involved in significantly more projects during the first time period than
      partners participating in the first time period only (Cohen's d = 0.93).
      DISCUSSION: This approach represents a significant step toward using objective
      (non-survey) data for large clusters of health partnerships and has implications
      for translational science in community settings. Considerations for government,
      funders, and communities are offered. Examining partnerships within health
      priority areas, orphaned projects, and faculty ties to these networks are areas
      for future research.

PMID- 25974415
TI  - Neuropathies after surgery: Anatomical considerations of pathologic mechanisms.
AB  - Positioning-related injuries caused during surgery under anesthesia are most
      likely multifactorial. Pathologic mechanical forces alone (overstretching and/or
      ischemia from direct compression) may not fully explain postsurgical neuropathy
      with recent evidence implicating patient-specific factors or perioperative
      inflammatory responses spatially and even temporally divorced from the anatomical
      region of injury. The aim of this introductory article is to provide an overview
      of anatomic considerations of these mechanical forces on soft and nervous tissues
      along with factors that may compound compression or stretch injury. Three
      subsequent articles will address specific positioning-related anatomic
      considerations of the (1) upper extremities, (2) lower extremities, and (3)
      central nervous system and soft tissues.

PMID- 25974414
TI  - Role of the Tau N-terminal region in microtubule stabilization revealed by new
      endogenous truncated forms.
AB  - Tau is a central player in Alzheimer's disease (AD) and related Tauopathies,
      where it is found as aggregates in degenerating neurons. Abnormal post
      translational modifications, such as truncation, are likely involved in the
      pathological process. A major step forward in understanding the role of Tau
      truncation would be to identify the precise cleavage sites of the several
      truncated Tau fragments that are observed until now in AD brains, especially
      those truncated at the N-terminus, which are less characterized than those
      truncated at the C-terminus. Here, we optimized a proteomics approach and
      succeeded in identifying a number of new N-terminally truncated Tau species from
      the human brain. We initiated cell-based functional studies by analyzing the
      biochemical characteristics of two N-terminally truncated Tau species starting at
      residues Met11 and Gln124 respectively. Our results show, interestingly, that the
      Gln124-Tau fragment displays a stronger ability to bind and stabilize
      microtubules, suggesting that the Tau N-terminal domain could play a direct role
      in the regulation of microtubule stabilization. Future studies based on our new N
      terminally truncated-Tau species should improve our knowledge of the role of
      truncation in Tau biology as well as in the AD pathological process. 

PMID- 25974416
TI  - Management of a Jehovah's Witness Patient with Sepsis and Profuse Bleeding After
      Emergency Coronary Artery Bypass Graft Surgery: Rethinking the Critical Threshold
      of Oxygen Delivery.
AB  - The duration and extent of acute hemodilution that the human body can withstand
      remains unclear. Many consider 184 mL/m/min to be the oxygen delivery (DO2)
      threshold below which oxygen consumption (VO2) begins to decrease. We describe a
      critically ill Jehovah's Witness patient who tolerated a much lower level of DO2,
      coupled with severe acute anemia that persisted for >10 days without any
      sequelae. This case challenges the currently accepted critical DO2 threshold and
      highlights the need for a comprehensive approach to increase DO2 and decrease VO2
      for best patient outcomes. Minimizing VO2, which is usually underemphasized in
      current clinical practice, probably played an important role in the survival of
      this patient. 

PMID- 25974417
TI  - Recovery from Extreme Hemodilution (Hemoglobin Level of 0.6 g/dL) in Cadaveric
      Liver Transplantation.
AB  - Decompensated hepatic failure occurred in a patient with a rare blood type. The
      patient had extreme hemodilution due to massive bleeding during liver
      transplantation. A shortage of matched and universal donor blood prompted us to
      transfuse albumin and fresh frozen plasma for intravascular volume resuscitation.
      The lowest hemoglobin was 0.6 g/dL, accompanied by ST depression and a serum
      lactate of 100 mg/dL. The accuracy of the measured value of 0.6 g/dL was
      confirmed. However, the patient recovered from this critical situation after
      transfusion, and he was eventually discharged from the hospital without
      significant sequelae. Maintaining normovolemia, administering pure oxygen,
      ensuring appropriate anesthetic depth, and maintaining minimal inotropic support
      were essential for this patient's survival during massive bleeding. 

PMID- 25974418
TI  - Editorial Comment: Recovery from Extreme Hemodilution (Hemoglobin Level of 0.6
      g/dL) in Cadaveric Liver Transplantation and Management of a Jehovah's Witness
      Patient with Sepsis and Profuse Bleeding After Emergency Coronary Artery Bypass
      Graft Surgery&colon; Rethinking the Critical Threshold of Oxygen Delivery.

PMID- 25974419
TI  - Bloodless Orthotopic Heart Transplantation in a Jehovah's Witness.
AB  - We present the case of a 53-year-old female Jehovah's Witness with nonischemic
      cardiomyopathy who successfully underwent a bloodless heart transplantation using
      fibrinogen concentrate (RiaSTAP; CSL Behring, King of Prussia, PA) and other
      blood-conservation methods. With a multidisciplinary team and the use of
      preoperative erythropoietin-stimulating drugs, normovolemic hemodilution, cell
      salvage, and pharmacotherapy to prevent and treat coagulopathy, we were able to
      maintain hemoglobin levels greater than 11 g/dL without the need for blood
      transfusion. We conclude that orthotopic heart transplants may be performed
      successfully in select Jehovah's Witness patients using standard and novel blood
      conservation methods.

PMID- 25974420
TI  - Editorial Comment: Bloodless Orthotopic Heart Transplantation in a Jehovah's
      Witness.

PMID- 25974421
TI  - Malnutrition in cirrhosis increases morbidity and mortality.
AB  - BACKGROUND AND AIMS: Malnutrition is frequent in patients with cirrhosis and is
      associated with complications like ascites, hepatic encephalopathy, infections,
      and death. We determined the prevalence of malnutrition by various methods and
      its clinical importance in patients with cirrhosis. METHODS: Consecutive patients
      of cirrhosis from August 2013 to February 2015 were assessed. Nutritional status
      was assessed by traditional model (mid-arm circumference, triceps skinfold
      thickness, serum albumin, creatinine height index, total lymphocyte count),
      handgrip, and body composition analysis measuring skeletal muscle mass and body
      fat mass. All patients were followed up for 12 months to assess the outcome.
      RESULTS: 247 patients (age 42.10 +/- 10.14 years, 81% male) were included in the
      study. Etiology of cirrhosis was alcohol in 53% patients. Prevalence of
      malnutrition was 59.5% according to traditional model, 66.8% by body composition
      analysis and 71.4% by handgrip. Nutritional status was poor in alcoholic
      cirrhotics versus nonalcoholics as assessed by triceps skinfold thickness (9.33
      +/- 2.9 vs 11.64 +/- 3.5 mm; P = 0.001), serum albumin (25.1 +/- 4 vs 28.1 +/- 4
      g/L; P = 0.001), and body fat mass (7.6 +/- 3.1 vs 8.7 +/- 3.3 kg; P = 0.008).
      Prevalence of malnutrition was 12/27 (44.5%), 96/131 (73.3%) and 84/89 (94.4%) in
      Child's class A, B, and C respectively. Complications requiring hospitalization
      (71.3% vs 38.2%; 0.002) and mortality (41.1% vs 18.2%; P = 0.001) were more in
      malnourished patients compared to well nourished. Nutritional assessment
      parameters significantly correlated with the liver disease severity (P < 0.05).
      CONCLUSIONS: Prevalence of malnutrition is high in patients with cirrhosis. It is
      associated with increased complications and mortality.

PMID- 25974422
TI  - C-reactive protein levels are associated with cerebral small vessel-related
      lesions.
AB  - OBJECTIVE: Inflammation has received increasing attention as a cause of stroke.
      Although several lines of evidence suggest that inflammatory processes have a
      role in arteriosclerotic vascular events, their involvement remains to be
      determined. The purpose of this study was to examine the associations between
      serum high-sensitive C-reactive protein (hs-CRP) levels and cerebral small vessel
      (CSV)-related lesions as a manifestation of arteriosclerosis. MATERIALS AND
      METHODS: Neurologically normal subjects without any history of neurologic or
      psychiatric diseases were enrolled (n = 519). All the participants underwent
      magnetic resonance imaging (MRI), and their CSV-related lesions (i.e., lacunar
      infarcts, cerebral microbleeds, deep white matter hyperintensity, and
      periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were
      evaluated as common inflammatory markers. RESULTS: Subjects with higher C
      reactive protein (CRP) levels had more lacunar infarcts (P = 0.02). After
      adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels
      were still associated with the presence of lacunar infarcts [odds ratio for the
      highest vs the lowest tertile of hs-CRP, 3.57 (95% confidence interval: 1.30
      9.80)]. These associations did not change when the logarithmically transformed
      values for hs-CRP were included. Furthermore, subjects with higher CRP levels had
      more cerebral microbleeds (P = 0.03), more severe deep white matter
      hyperintensity (P = 0.04), and periventricular hyperintensity (P = 0.04);
      however, these associations were not observed after adjusting for the
      cardiovascular risk factors. CONCLUSIONS: Higher levels of hs-CRP were associated
      with lacunar infarcts. Thus, inflammatory processes may be involved in the
      pathogenesis of small-vessel disease.

PMID- 25974424
TI  - Granger causality for state-space models.
AB  - Granger causality has long been a prominent method for inferring causal
      interactions between stochastic variables for a broad range of complex physical
      systems. However, it has been recognized that a moving average (MA) component in
      the data presents a serious confound to Granger causal analysis, as routinely
      performed via autoregressive (AR) modeling. We solve this problem by
      demonstrating that Granger causality may be calculated simply and efficiently
      from the parameters of a state-space (SS) model. Since SS models are equivalent
      to autoregressive moving average models, Granger causality estimated in this
      fashion is not degraded by the presence of a MA component. This is of particular
      significance when the data has been filtered, downsampled, observed with noise,
      or is a subprocess of a higher dimensional process, since all of these operations
      commonplace in application domains as diverse as climate science, econometrics,
      and the neurosciences-induce a MA component. We show how Granger causality,
      conditional and unconditional, in both time and frequency domains, may be
      calculated directly from SS model parameters via solution of a discrete algebraic
      Riccati equation. Numerical simulations demonstrate that Granger causality
      estimators thus derived have greater statistical power and smaller bias than AR
      estimators. We also discuss how the SS approach facilitates relaxation of the
      assumptions of linearity, stationarity, and homoscedasticity underlying current
      AR methods, thus opening up potentially significant new areas of research in
      Granger causal analysis. 

PMID- 25974423
TI  - Two Hydroxyproline Galactosyltransferases, GALT5 and GALT2, Function in
      Arabinogalactan-Protein Glycosylation, Growth and Development in Arabidopsis.
AB  - Hydroxyproline-O-galactosyltransferase (GALT) initiates O-glycosylation of
      arabinogalactan-proteins (AGPs). We previously characterized GALT2 (At4g21060),
      and now report on functional characterization of GALT5 (At1g74800). GALT5 was
      identified using heterologous expression in Pichia and an in vitro GALT assay.
      Product characterization showed GALT5 specifically adds galactose to
      hydroxyproline in AGP protein backbones. Functions of GALT2 and GALT5 were
      elucidated by phenotypic analysis of single and double mutant plants. Allelic
      galt5 and galt2 mutants, and particularly galt2 galt5 double mutants,
      demonstrated lower GALT activities and reductions in beta-Yariv-precipitated AGPs
      compared to wild type. Mutant plants showed pleiotropic growth and development
      phenotypes (defects in root hair growth, root elongation, pollen tube growth,
      flowering time, leaf development, silique length, and inflorescence growth),
      which were most severe in the double mutants. Conditional mutant phenotypes were
      also observed, including salt-hypersensitive root growth and root tip swelling as
      well as reduced inhibition of pollen tube growth and root growth in response to
      beta-Yariv reagent. These mutants also phenocopy mutants for an AGP, SOS5, and
      two cell wall receptor-like kinases, FEI1 and FEI2, which exist in a genetic
      signaling pathway. In summary, GALT5 and GALT2 function as redundant GALTs that
      control AGP O-glycosylation, which is essential for normal growth and
      development. 

PMID- 25974426
TI  - Geometry-guided colloidal interactions and self-tiling of elastic dipoles formed
      by truncated pyramid particles in liquid crystals.
AB  - The progress of realizing colloidal structures mimicking natural forms of
      organization in condensed matter is inherently limited by the availability of
      suitable colloidal building blocks. To enable new forms of crystalline and
      quasicrystalline self-organization of colloids, we develop truncated pyramidal
      particles that form nematic elastic dipoles with long-range electrostaticlike and
      geometry-guided low-symmetry short-range interactions. Using a combination of
      nonlinear optical imaging, laser tweezers, and video microscopy, we characterize
      colloidal pair interactions and demonstrate unusual forms of self-tiling of these
      particles into crystalline, quasicrystalline, and other arrays. Our findings are
      explained using an electrostatics analogy along with liquid crystal elasticity
      and symmetry breaking considerations, potentially expanding photonic and electro
      optic applications of colloids. 

PMID- 25974425
TI  - Coherent energy transport in classical nonlinear oscillators: An analogy with the
      Josephson effect.
AB  - By means of a simple theoretical model and numerical simulations, we demonstrate
      the presence of persistent energy currents in a lattice of classical nonlinear
      oscillators with uniform temperature and chemical potential. In analogy with the
      well-known Josephson effect, the currents are proportional to the sine of the
      phase differences between the oscillators. Our results elucidate general aspects
      of nonequilibrium thermodynamics and point towards a way to practically control
      transport phenomena in a large class of systems. We apply the model to describe
      the phase-controlled spin-wave current in a bilayer nanopillar. 

PMID- 25974427
TI  - Stochastic synchronization of neural activity waves.
AB  - We demonstrate that waves in distinct layers of a neuronal network can become
      phase locked by common spatiotemporal noise. This phenomenon is studied for
      stationary bumps, traveling waves, and breathers. A weak noise expansion is used
      to derive an effective equation for the position of the wave in each layer,
      yielding a stochastic differential equation with multiplicative noise. Stability
      of the synchronous state is characterized by a Lyapunov exponent, which we can
      compute analytically from the reduced system. Our results extend previous work on
      limit-cycle oscillators, showing common noise can synchronize waves in a broad
      class of models. 

PMID- 25974428
TI  - Amplitude-phase coupling drives chimera states in globally coupled laser
      networks.
AB  - For a globally coupled network of semiconductor lasers with delayed optical
      feedback, we demonstrate the existence of chimera states. The domains of
      coherence and incoherence that are typical for chimera states are found to exist
      for the amplitude, phase, and inversion of the coupled lasers. These chimera
      states defy several of the previously established existence criteria. While
      chimera states in phase oscillators generally demand nonlocal coupling, large
      system sizes, and specially prepared initial conditions, we find chimera states
      that are stable for global coupling in a network of only four coupled lasers for
      random initial conditions. The existence is linked to a regime of multistability
      between the synchronous steady state and asynchronous periodic solutions. We show
      that amplitude-phase coupling, a concept common in different fields, is necessary
      for the formation of the chimera states. 

PMID- 25974429
TI  - Generation of magnetic fields by large-scale vortices in rotating convection.
AB  - We propose a self-consistent dynamo mechanism for the generation of large-scale
      magnetic fields in natural objects. Recent computational studies have described
      the formation of large-scale vortices in rotating turbulent convection. Here we
      demonstrate that for magnetic Reynolds numbers below the threshold for small
      scale dynamo action, such turbulent flows can sustain large-scale magnetic
      fields, i.e., fields with a significant component on the scale of the system. 

PMID- 25974430
TI  - Effect of weak fluid inertia upon Jeffery orbits.
AB  - We consider the rotation of small neutrally buoyant axisymmetric particles in a
      viscous steady shear flow. When inertial effects are negligible the problem
      exhibits infinitely many periodic solutions, the "Jeffery orbits." We compute how
      inertial effects lift their degeneracy by perturbatively solving the coupled
      particle-flow equations. We obtain an equation of motion valid at small shear
      Reynolds numbers, for spheroidal particles with arbitrary aspect ratios. We
      analyze how the linear stability of the "log-rolling" orbit depends on particle
      shape and find it to be unstable for prolate spheroids. This resolves a puzzle in
      the interpretation of direct numerical simulations of the problem. In general,
      both unsteady and nonlinear terms in the Navier-Stokes equations are important. 

PMID- 25974431
TI  - Crisis bifurcations in plane Poiseuille flow.
AB  - Many shear flows follow a route to turbulence that has striking similarities to
      bifurcation scenarios in low-dimensional dynamical systems. Among the
      bifurcations that appear, crisis bifurcations are important because they cause
      global transitions between open and closed attractors, or indicate drastic
      increases in the range of the state space that is covered by the dynamics. We
      here study exterior and interior crisis bifurcations in direct numerical
      simulations of transitional plane Poiseuille flow in a mirror-symmetric subspace.
      We trace the state space dynamics from the appearance of the first three
      dimensional exact coherent structures to the transition from an attractor to a
      chaotic saddle in an exterior crisis. For intermediate Reynolds numbers, the
      attractor undergoes several interior crises, in which new states appear and
      intermittent behavior can be observed. The bifurcations contribute to increasing
      the complexity of the dynamics and to a more dense coverage of state space. 

PMID- 25974432
TI  - Nondiffusive transport regimes for suprathermal ions in turbulent plasmas.
AB  - The understanding of the transport of suprathermal ions in the presence of
      turbulence is important for fusion plasmas in the burning regime that will
      characterize reactors, and for space plasmas to understand the physics of
      particle acceleration. Here, three-dimensional measurements of a suprathermal ion
      beam in the toroidal plasma device TORPEX are presented. These measurements
      demonstrate, in a turbulent plasma, the existence of subdiffusive and
      superdiffusive transport of suprathermal ions, depending on their energy. This
      result stems from the unprecedented combination of uniquely resolved measurements
      and first-principles numerical simulations that reveal the mechanisms responsible
      for the nondiffusive transport. The transport regime is determined by the
      interaction of the suprathermal ion orbits with the turbulent plasma dynamics,
      and is strongly affected by the ratio of the suprathermal ion energy to the
      background plasma temperature. 

PMID- 25974433
TI  - Cascades in nonlocal turbulence.
AB  - We consider developed turbulence in the two-dimensional Gross-Pitaevskii model,
      which describes wide classes of phenomena from atomic and optical physics to
      condensed matter, fluids, and plasma. The well-known difficulty of the problem is
      that the hypothetical local spectra of both inverse and direct cascades in the
      weak-turbulence approximation carry fluxes that are either zero or have the wrong
      sign; Such spectra cannot be realized. We analytically derive the exact flux
      constancy laws (analogs of Kolmogorov's 4/5 law for incompressible fluid
      turbulence), expressed via the fourth-order moment and valid for any
      nonlinearity. We confirm the flux laws in direct numerical simulations. We show
      that a constant flux is realized by a nonlocal wave interaction in both the
      direct and inverse cascades. Wave spectra (second-order moments) are close to
      slightly (logarithmically) distorted thermal equilibrium in both cascades. 

PMID- 25974434
TI  - Crucial role of strategy updating for coexistence of strategies in interaction
      networks.
AB  - Network models are useful tools for studying the dynamics of social interactions
      in a structured population. After a round of interactions with the players in
      their local neighborhood, players update their strategy based on the comparison
      of their own payoff with the payoff of one of their neighbors. Here we show that
      the assumptions made on strategy updating are of crucial importance for the
      strategy dynamics. In the first step, we demonstrate that seemingly small
      deviations from the standard assumptions on updating have major implications for
      the evolutionary outcome of two cooperation games: cooperation can more easily
      persist in a Prisoner's Dilemma game, while it can go more easily extinct in a
      Snowdrift game. To explain these outcomes, we develop a general model for the
      updating of states in a network that allows us to derive conditions for the
      steady-state coexistence of states (or strategies). The analysis reveals that
      coexistence crucially depends on the number of agents consulted for updating. We
      conclude that updating rules are as important for evolution on a network as
      network structure and the nature of the interaction. 

PMID- 25974435
TI  - Extreme Thouless effect in a minimal model of dynamic social networks.
AB  - In common descriptions of phase transitions, first-order transitions are
      characterized by discontinuous jumps in the order parameter and normal
      fluctuations, while second-order transitions are associated with no jumps and
      anomalous fluctuations. Outside this paradigm are systems exhibiting "mixed
      order" transitions displaying a mixture of these characteristics. When the jump
      is maximal and the fluctuations range over the entire range of allowed values,
      the behavior has been coined an "extreme Thouless effect." Here we report
      findings of such a phenomenon in the context of dynamic, social networks. Defined
      by minimal rules of evolution, it describes a population of extreme introverts
      and extroverts, who prefer to have contacts with, respectively, no one or
      everyone. From the dynamics, we derive an exact distribution of microstates in
      the stationary state. With only two control parameters, N(I,E) (the number of
      each subgroup), we study collective variables of interest, e.g., X, the total
      number of I-E links, and the degree distributions. Using simulations and mean
      field theory, we provide evidence that this system displays an extreme Thouless
      effect. Specifically, the fraction X/(N(I)N(E)) jumps from 0 to 1 (in the
      thermodynamic limit) when N(I) crosses N(E), while all values appear with equal
      probability at N(I)=N(E).

PMID- 25974436
TI  - Langevin dynamics for vector variables driven by multiplicative white noise: A
      functional formalism.
AB  - We discuss general multidimensional stochastic processes driven by a system of
      Langevin equations with multiplicative white noise. In particular, we address the
      problem of how time reversal diffusion processes are affected by the variety of
      conventions available to deal with stochastic integrals. We present a functional
      formalism to build up the generating functional of correlation functions without
      any type of discretization of the Langevin equations at any intermediate step.
      The generating functional is characterized by a functional integration over two
      sets of commuting variables, as well as Grassmann variables. In this
      representation, time reversal transformation became a linear transformation in
      the extended variables, simplifying in this way the complexity introduced by the
      mixture of prescriptions and the associated calculus rules. The stochastic
      calculus is codified in our formalism in the structure of the Grassmann algebra.
      We study some examples such as higher order derivative Langevin equations and the
      functional representation of the micromagnetic stochastic Landau-Lifshitz-Gilbert
      equation. 

PMID- 25974437
TI  - Efimov-like phase of a three-stranded DNA and the renormalization-group limit
      cycle.
AB  - A three-stranded DNA with short range base pairings only is known to exhibit a
      classical analog of the quantum Efimov effect, viz., a three-chain bound state at
      the two-chain melting point where no two are bound. By using a nonperturbative
      renormalization-group method for a rigid duplex DNA and a flexible third strand,
      with base pairings and strand exchange, we show that the Efimov-DNA is associated
      with a limit cycle type behavior of the flow of an effective three-chain
      interaction. The analysis also shows that thermally generated bubbles play an
      essential role in producing the effect. A toy model for the flow equations shows
      the limit cycle in an extended three-dimensional parameter space of the two-chain
      coupling and a complex three-chain interaction. 

PMID- 25974438
TI  - Network reciprocity created in prisoner's dilemma games by coupling two
      mechanisms.
AB  - We found that a nontrivial enhancement of network reciprocity for 2 * 2
      prisoner's dilemma games can be achieved by coupling two mechanisms. The first
      mechanism presumes a larger strategy update neighborhood than the conventional
      first neighborhood on the underlying network. The second is the strategy-shifting
      rule. At the initial time step, the averaged cooperation extent is assumed to be
      0.5. In the case of strategy shifting, an agent adopts a continuous strategy
      definition during the initial period of a simulation episode (when the global
      cooperation fraction decreases from its initial value of 0.5; that is, the
      enduring period). The agent then switches to a discrete strategy definition in
      the time period afterwards (when the global cooperation fraction begins to
      increase again; that is, the expanding period). We explored why this particular
      enhancement comes about, and to summarize, the continuous strategy during the
      initial period relaxes the conditions for the survival of relatively cooperative
      clusters, and the large strategy adaptation neighborhood allows those cooperative
      clusters to expand easily. 

PMID- 25974439
TI  - Aging scaled Brownian motion.
AB  - Scaled Brownian motion (SBM) is widely used to model anomalous diffusion of
      passive tracers in complex and biological systems. It is a highly nonstationary
      process governed by the Langevin equation for Brownian motion, however, with a
      power-law time dependence of the noise strength. Here we study the aging
      properties of SBM for both unconfined and confined motion. Specifically, we
      derive the ensemble and time averaged mean squared displacements and analyze
      their behavior in the regimes of weak, intermediate, and strong aging. A very
      rich behavior is revealed for confined aging SBM depending on different aging
      times and whether the process is sub- or superdiffusive. We demonstrate that the
      information on the aging factorizes with respect to the lag time and exhibits a
      functional form that is identical to the aging behavior of scale-free continuous
      time random walk processes. While SBM exhibits a disparity between ensemble and
      time averaged observables and is thus weakly nonergodic, strong aging is shown to
      effect a convergence of the ensemble and time averaged mean squared displacement.
      Finally, we derive the density of first passage times in the semi-infinite domain
      that features a crossover defined by the aging time. 

PMID- 25974440
TI  - Work relations connecting nonequilibrium steady states without detailed balance.
AB  - Bridging equilibrium and nonequilibrium statistical physics attracts sustained
      interest. Hallmarks of nonequilibrium systems include a breakdown of detailed
      balance, and an absence of a priori potential function corresponding to the
      Boltzmann-Gibbs distribution, without which classical equilibrium thermodynamical
      quantities could not be defined. Here, we construct dynamically the potential
      function through decomposing the system into a dissipative part and a
      conservative part, and develop a nonequilibrium theory by defining
      thermodynamical quantities based on the potential function. Concepts for
      equilibrium can thus be naturally extended to nonequilibrium steady state. We
      elucidate this procedure explicitly in a class of time-dependent linear diffusive
      systems without mathematical ambiguity. We further obtain the exact work
      distribution for an arbitrary control parameter, and work equalities connecting
      nonequilibrium steady states. Our results provide a direct generalization on
      Jarzynski equality and Crooks fluctuation theorem to systems without detailed
      balance. 

PMID- 25974441
TI  - Quantum diffusion of a relativistic particle in a time-dependent random
      potential.
AB  - We present a rigorous study of quantum diffusion of a relativistic particle
      subjected to a time-dependent random potential with delta correlation in time. We
      find that in the asymptotic time limit the particle wave packet spreads
      ballistically in contrast with the nonrelativistic case, which in the same
      situation exhibits superballistic diffusion. The relativistic suppression of wave
      packet diffusion is discussed in connection with statistical conservation laws
      that follow from relativistic dynamics. 

PMID- 25974442
TI  - Nonsynchronous updating in the multiverse of cellular automata.
AB  - In this paper we study updating effects on cellular automata rule space. We
      consider a subset of 6144 order-3 automata from the space of 262144 bidimensional
      outer-totalistic rules. We compare synchronous to asynchronous and sequential
      updatings. Focusing on two automata, we discuss how update changes destroy
      typical structures of these rules. Besides, we show that the first-order phase
      transition in the multiverse of synchronous cellular automata, revealed with the
      use of a recently introduced control parameter, seems to be robust not only to
      changes in update schema but also to different initial densities. 

PMID- 25974443
TI  - Noise-induced multistability in chemical systems: Discrete versus continuum
      modeling.
AB  - The noisy dynamics of chemical systems is commonly studied using either the
      chemical master equation (CME) or the chemical Fokker-Planck equation (CFPE). The
      latter is a continuum approximation of the discrete CME approach. It has recently
      been shown that for a particular system, the CFPE captures noise-induced
      multistability predicted by the CME. This phenomenon involves the CME's marginal
      probability distribution changing from unimodal to multimodal as the system size
      decreases below a critical value. We here show that the CFPE does not always
      capture noise-induced multistability. In particular we find simple chemical
      systems for which the CME predicts noise-induced multistability, whereas the CFPE
      predicts monostability for all system sizes. 

PMID- 25974444
TI  - Subdiffusion in an external potential: Anomalous effects hiding behind normal
      behavior.
AB  - We propose a model of subdiffusion in which an external force is acting on a
      particle at all times not only at the moment of jump. The implication of this
      assumption is the dependence of the random trapping time on the force with the
      dramatic change of particles behavior compared to the standard continuous time
      random walk model in the long time limit. Constant force leads to the transition
      from non-ergodic subdiffusion to ergodic diffusive behavior. However, we show
      this behavior remains anomalous in a sense that the diffusion coefficient depends
      on the external force and on the anomalous exponent. For quadratic potential we
      find that the system remains non-ergodic. The anomalous exponent in this case
      defines not only the speed of convergence but also the stationary distribution
      which is different from standard Boltzmann equilibrium. 

PMID- 25974445
TI  - Domain-size heterogeneity in the Ising model: Geometrical and thermal
      transitions.
AB  - A measure of cluster size heterogeneity (H), introduced by Lee et al. [Phys. Rev.
      E 84, 020101 (2011)] in the context of explosive percolation, was recently
      applied to random percolation and to domains of parallel spins in the Ising and
      Potts models. It is defined as the average number of different domain sizes in a
      given configuration and a new exponent was introduced to explain its scaling with
      the size of the system. In thermal spin models, however, physical clusters take
      into account the temperature-dependent correlation between neighboring spins and
      encode the critical properties of the phase transition. We here extend the
      measure of H to these clusters and, moreover, present new results for the
      geometric domains for both d=2 and 3. We show that the heterogeneity associated
      with geometric domains has a previously unnoticed double peak, thus being able to
      detect both the thermal and percolative transitions. An alternative
      interpretation for the scaling of H that does not introduce a new exponent is
      also proposed.

PMID- 25974446
TI  - Stochastic thermodynamics of Langevin systems under time-delayed feedback
      control: Second-law-like inequalities.
AB  - Response lags are generic to almost any physical system and often play a crucial
      role in the feedback loops present in artificial nanodevices and biological
      molecular machines. In this paper, we perform a comprehensive study of small
      stochastic systems governed by an underdamped Langevin equation and driven out of
      equilibrium by a time-delayed continuous feedback control. In their normal
      operating regime, these systems settle in a nonequilibrium steady state in which
      work is permanently extracted from the surrounding heat bath. By using the Fokker
      Planck representation of the dynamics, we derive a set of second-law-like
      inequalities that provide bounds to the rate of extracted work. These
      inequalities involve additional contributions characterizing the reduction of
      entropy production due to the continuous measurement process. We also show that
      the non-Markovian nature of the dynamics requires a modification of the basic
      relation linking dissipation to the breaking of time-reversal symmetry at the
      level of trajectories. The modified relation includes a contribution arising from
      the acausal character of the reverse process. This, in turn, leads to another
      second-law-like inequality. We illustrate the general formalism with a detailed
      analytical and numerical study of a harmonic oscillator driven by a linear
      feedback, which describes actual experimental setups. 

PMID- 25974447
TI  - Goldstein-Kac telegraph processes with random speeds: Path probabilities,
      likelihoods, and reported Levy flights.
AB  - The Goldstein-Kac telegraph process describes the one-dimensional motion of
      particles with constant speed undergoing random changes in direction. Despite its
      resemblance to numerous real-world phenomena, the singular nature of the
      resultant spatial distribution of each particle precludes the possibility of any
      a posteriori empirical validation of this random-walk model from data. Here we
      show that by simply allowing for random speeds, the ballistic terms are
      regularized and that the diffusion component can be well-approximated via the
      unscented transform. The result is a computationally efficient yet robust
      evaluation of the full particle path probabilities and, hence, the parameter
      likelihoods of this generalized telegraph process. We demonstrate how a
      population diffusing under such a model can lead to non-Gaussian asymptotic
      spatial distributions, thereby mimicking the behavior of an ensemble of Levy
      walkers. 

PMID- 25974448
TI  - Thermal transport in out-of-equilibrium quantum harmonic chains.
AB  - We address the problem of heat transport in a chain of coupled quantum harmonic
      oscillators, exposed to the influences of local environments of various nature,
      stressing the effects that the specific nature of the environment has on the
      phenomenology of the transport process. We study in detail the behavior of
      thermodynamically relevant quantities such as heat currents and mean energies of
      the oscillators, establishing rigorous analytical conditions for the existence of
      a steady state, whose features we analyze carefully. In particular, we assess the
      conditions that should be faced to recover trends reminiscent of the classical
      Fourier law of heat conduction and highlight how such a possibility depends on
      the environment linked to our system. 

PMID- 25974449
TI  - Glass transitions and scaling laws within an alternative mode-coupling theory.
AB  - Idealized glass transitions are discussed within an alternative mode-coupling
      theory (TMCT) proposed by Tokuyama [Physica A 395, 31 (2014)]. This is done in
      order to identify common ground with and differences from the conventional mode
      coupling theory (MCT). It is proven that both theories imply the same scaling
      laws for the transition dynamics, which are characterized by two power-law decay
      functions and two diverging power-law time scales. However, the values for the
      corresponding anomalous exponents calculated within both theories differ from
      each other. It is proven that the TMCT, contrary to the MCT, does not describe
      transitions with continuously vanishing arrested parts of the correlation
      functions. It is also demonstrated for a schematic model that the TMCT does not
      lead to the MCT scenarios either for transition-line crossings or for the
      appearance of higher-order glass-transition singularities.

PMID- 25974450
TI  - Far-from-equilibrium growth of magnetic thin films with Blume-Capel impurities.
AB  - We investigate the irreversible growth of (2+1)-dimensional magnetic thin films.
      The spin variable can adopt three states (s(I)=+/-1,0), and the system is in
      contact with a thermal bath of temperature T. The deposition process depends on
      the change of the configuration energy, which, by analogy to the Blume-Capel
      Hamiltonian in equilibrium systems, depends on Ising-like couplings between
      neighboring spins (J) and has a crystal field (D) term that controls the density
      of nonmagnetic impurities (s(I)=0). Once deposited, particles are not allowed to
      flip, diffuse, or detach. By means of extensive Monte Carlo simulations, we
      obtain the phase diagram in the crystal field vs temperature parameter space. We
      show clear evidence of the existence of a tricritical point located at
      D(t)/J=1.145(10) and k(B)T(t)/J=0.425(10), which separates a first-order
      transition curve at lower temperatures from a critical second-order transition
      curve at higher temperatures, in analogy with the previously studied equilibrium
      Blume-Capel model. Furthermore, we show that, along the second-order transition
      curve, the critical behavior of the irreversible growth model can be described by
      means of the critical exponents of the two-dimensional Ising model under
      equilibrium conditions. Therefore, our findings provide a link between well-known
      theoretical equilibrium models and nonequilibrium growth processes that are of
      great interest for many experimental applications, as well as a paradigmatic
      topic of study in current statistical physics.

PMID- 25974451
TI  - Nonbacktracking operator for the Ising model and its applications in systems with
      multiple states.
AB  - The nonbacktracking operator for a graph is the adjacency matrix defined on
      directed edges of the graph. The operator was recently shown to perform optimally
      in spectral clustering in sparse synthetic graphs and have a deep connection to
      belief propagation algorithm. In this paper we consider nonbacktracking operator
      for Ising model on a general graph with a general coupling distribution and study
      the spectrum of this operator analytically. We show that spectral algorithms
      based on this operator is equivalent to belief propagation algorithm linearized
      at the paramagnetic fixed point and recovers replica-symmetry results on phase
      boundaries obtained by replica methods. This operator can be applied directly to
      systems with multiple states like Hopfield model. We show that spectrum of the
      operator can be used to determine number of patterns that stored successfully in
      the network, and the associated eigenvectors can be used to retrieve all the
      patterns simultaneously. We also give an example on how to control the Hopfield
      model, i.e., making network more sparse while keeping patterns stable, using the
      nonbacktracking operator and matrix perturbation theory. 

PMID- 25974452
TI  - Evidence for nonuniversal scaling in dimension-four Ising spin glasses.
AB  - The critical behavior of the Binder cumulant for Ising spin glasses in dimension
      four is studied through simulation measurements. Data for the bimodal interaction
      model are compared with those for the Laplacian interaction model. Special
      attention is paid to scaling corrections. The limiting infinite size value at
      criticality for this dimensionless variable is a parameter characteristic of a
      universality class. This critical limit is estimated to be equal to 0.523(3) in
      the bimodal model and to 0.473(3) in the Laplacian model. 

PMID- 25974453
TI  - Finite-size scaling of survival probability in branching processes.
AB  - Branching processes pervade many models in statistical physics. We investigate
      the survival probability of a Galton-Watson branching process after a finite
      number of generations. We derive analytically the existence of finite-size
      scaling for the survival probability as a function of the control parameter and
      the maximum number of generations, obtaining the critical exponents as well as
      the exact scaling function, which is G(y)=2ye(y)/(e(y)-1), with y the rescaled
      distance to the critical point. Our findings are valid for any branching process
      of the Galton-Watson type, independently of the distribution of the number of
      offspring, provided its variance is finite. This proves the universal behavior of
      the finite-size effects in branching processes, including the universality of the
      metric factors. The direct relation to mean-field percolation is also discussed.

PMID- 25974454
TI  - Quantum transitions driven by one-bond defects in quantum Ising rings.
AB  - We investigate quantum scaling phenomena driven by lower-dimensional defects in
      quantum Ising-like models. We consider quantum Ising rings in the presence of a
      bond defect. In the ordered phase, the system undergoes a quantum transition
      driven by the bond defect between a magnet phase, in which the gap decreases
      exponentially with increasing size, and a kink phase, in which the gap decreases
      instead with a power of the size. Close to the transition, the system shows a
      universal scaling behavior, which we characterize by computing, either
      analytically or numerically, scaling functions for the low-level energy
      differences and the two-point correlation function. We discuss the implications
      of these results for the nonequilibrium dynamics in the presence of a slowly
      varying parallel magnetic field h, when going across the first-order quantum
      transition at h=0. 

PMID- 25974455
TI  - Persistent random walk of cells involving anomalous effects and random death.
AB  - The purpose of this paper is to implement a random death process into a
      persistent random walk model which produces sub-ballistic superdiffusion (Levy
      walk). We develop a stochastic two-velocity jump model of cell motility for which
      the switching rate depends upon the time which the cell has spent moving in one
      direction. It is assumed that the switching rate is a decreasing function of
      residence (running) time. This assumption leads to the power law for the velocity
      switching time distribution. This describes the anomalous persistence of cell
      motility: the longer the cell moves in one direction, the smaller the switching
      probability to another direction becomes. We derive master equations for the cell
      densities with the generalized switching terms involving the tempered fractional
      material derivatives. We show that the random death of cells has an important
      implication for the transport process through tempering of the superdiffusive
      process. In the long-time limit we write stationary master equations in terms of
      exponentially truncated fractional derivatives in which the rate of death plays
      the role of tempering of a Levy jump distribution. We find the upper and lower
      bounds for the stationary profiles corresponding to the ballistic transport and
      diffusion with the death-rate-dependent diffusion coefficient. Monte Carlo
      simulations confirm these bounds. 

PMID- 25974456
TI  - Thermal transport in phononic Cayley-tree networks.
AB  - We analytically investigate the heat current I and its thermal fluctuations Delta
      in a branching network without loops (Cayley tree). The network consists of two
      types of harmonic masses: vertex masses M placed at the branching points where
      phononic scattering occurs and masses m at the bonds between branching points
      where phonon propagation takes place. The network is coupled to thermal
      reservoirs consisting of one-dimensional harmonic chains of coupled masses m. Due
      to impedance mismatch phenomena, both I and Delta are non-monotonic functions of
      the mass ratio MU=M/m. Furthermore, we find that in the low-temperature limit the
      thermal conductance approaches zero faster than linearly due to the small
      transmittance of the long-wavelength modes. 

PMID- 25974457
TI  - Diffusion in the presence of scale-free absorbing boundaries.
AB  - Scale-free surfaces, such as cones, remain unchanged under a simultaneous
      expansion of all coordinates by the same factor. Probability density of a
      particle diffusing near such absorbing surface at large time approaches a simple
      form that incorporates power-law dependencies on time and distance from a special
      point, such as apex of the cone, which are characterized by a single exponent
      eta. The same exponent is used to describe the number of spatial conformations of
      long ideal polymer attached to the special point of a repulsive surface of the
      same geometry and can be used in calculation of entropic forces between such
      polymers and surfaces. We use the solution of diffusion equation near such
      surfaces to find the numerical values of eta, as well as to provide some insight
      into the behavior of ideal polymers near such surfaces. 

PMID- 25974458
TI  - Unified trade-off optimization for general heat devices with nonisothermal
      processes.
AB  - An analysis of the efficiency and coefficient of performance (COP) for general
      heat engines and refrigerators with nonisothermal processes is conducted under
      the trade-off criterion. The specific heat of the working medium has significant
      impacts on the optimal configurations of heat devices. For cycles with constant
      specific heat, the bounds of the efficiency and COP are found to be the same as
      those obtained through the endoreversible Carnot ones. However, they are
      independent of the cycle time durations. For cycles with nonconstant specific
      heat, whose dimensionless contact time approaches infinity, the general
      alternative upper and lower bounds of the efficiency and COP under the trade-off
      criteria have been proposed under the asymmetric limits. Furthermore, when the
      dimensionless contact time approaches zero, the endoreversible Carnot model is
      recovered. In addition, the efficiency and COP bounds of different kinds of
      actual heat engines and refrigerators have also been analyzed. This paper may
      provide practical insight for designing and operating actual heat engines and
      refrigerators. 

PMID- 25974459
TI  - Ground states for nonuniform periodic Ising chains.
AB  - We generalize Morita's works [J. Phys. A 7, 289 (1974); J. Phys. A 7, 1613
      (1974)] on ground states of Ising chains, for chains with a periodic structure
      and different spins, to any interaction order. The main assumption is
      translational invariance. The length of the irreducible blocks is a multiple of
      the period of the chain. If there is parity invariance, it restricts the length
      in general only in the diatomic case. There are degenerated states and under
      certain circumstances there could be nonregular ground states. We illustrate the
      results and give the ground state diagrams in several cases.

PMID- 25974460
TI  - Coexistence of energy diffusion and local thermalization in nonequilibrium XXZ
      spin chains with integrability breaking.
AB  - In this work we analyze the simultaneous emergence of diffusive energy transport
      and local thermalization in a nonequilibrium one-dimensional quantum system, as a
      result of integrability breaking. Specifically, we discuss the local properties
      of the steady state induced by thermal boundary driving in a XXZ spin chain with
      staggered magnetic field. By means of efficient large-scale matrix product
      simulations of the equation of motion of the system, we calculate its steady
      state in the long-time limit. We start by discussing the energy transport
      supported by the system, finding it to be ballistic in the integrable limit and
      diffusive when the staggered field is finite. Subsequently, we examine the
      reduced density operators of neighboring sites and find that for large systems
      they are well approximated by local thermal states of the underlying Hamiltonian
      in the nonintegrable regime, even for weak staggered fields. In the integrable
      limit, on the other hand, this behavior is lost, and the identification of local
      temperatures is no longer possible. Our results agree with the intuitive
      connection between energy diffusion and thermalization. 

PMID- 25974461
TI  - Inverting the Achlioptas rule for explosive percolation.
AB  - In the usual Achlioptas processes the smallest clusters of a few randomly chosen
      ones are selected to merge together at each step. The resulting aggregation
      process leads to the delayed birth of a giant cluster and the so-called explosive
      percolation transition showing a set of anomalous features. We explore a process
      with the opposite selection rule, in which the biggest clusters of the randomly
      chosen ones merge together. We develop a theory of this kind of percolation based
      on the Smoluchowsky equation, find the percolation threshold, and describe the
      scaling properties of this continuous transition, namely, the critical exponents
      and amplitudes, and scaling functions. We show that, qualitatively, this
      transition is similar to the ordinary percolation one, though occurring in less
      connected systems. 

PMID- 25974463
TI  - Ferromagnetism, antiferromagnetism, and the curious nematic phase of S=1 quantum
      spin systems.
AB  - We investigate the phase diagram of S=1 quantum spin systems with SU(2)-invariant
      interactions, at low temperatures and in three spatial dimensions. Symmetry
      breaking and the nature of extremal states can be studied using random loop
      representations. The latter confirm the occurrence of ferro- and
      antiferromagnetic transitions and the breaking of SU(3) invariance. And they
      reveal the peculiar nature of the nematic extremal states which minimize
      ?(x)(S(x)(I))(2).

PMID- 25974462
TI  - Spatial extent of branching Brownian motion.
AB  - We study the one-dimensional branching Brownian motion starting at the origin and
      investigate the correlation between the rightmost (X(max)>=0) and leftmost
      (X(min)<=0) visited sites up to time t. At each time step the existing particles
      in the system either diffuse (with diffusion constant D), die (with rate a), or
      split into two particles (with rate b). We focus on the regime b<=a where these
      two extreme values X(max) and X(min) are strongly correlated. We show that at
      large time t, the joint probability distribution function (PDF) of the two
      extreme points becomes stationary P(X,Y,t->infinity)->p(X,Y). Our exact results
      for p(X,Y) demonstrate that the correlation between X(max) and X(min) is nonzero,
      even in the stationary state. From this joint PDF, we compute exactly the
      stationary PDF p(zeta) of the (dimensionless) span zeta=(X(max)-X(min))/?[D/b],
      which is the distance between the rightmost and leftmost visited sites. This span
      distribution is characterized by a linear behavior p(zeta)~1/2(1+Delta)zeta for
      small spans, with Delta=(a/b-1). In the critical case (Delta=0) this distribution
      has a nontrivial power law tail p(zeta)~8pi?[3]/zeta(3) for large spans. On the
      other hand, in the subcritical case (Delta>0), we show that the span distribution
      decays exponentially as p(zeta)~(A(2)/2)zetaexp(-?[Delta]zeta) for large spans,
      where A is a nontrivial function of Delta, which we compute exactly. We show that
      these asymptotic behaviors carry the signatures of the correlation between X(max)
      and X(min). Finally we verify our results via direct Monte Carlo simulations.

PMID- 25974464
TI  - Leaf-to-leaf distances and their moments in finite and infinite ordered m-ary
      tree graphs.
AB  - We study the leaf-to-leaf distances on one-dimensionally ordered, full and
      complete m-ary tree graphs using a recursive approach. In our formulation, unlike
      in traditional graph theory approaches, leaves are ordered along a line emulating
      a one-dimensional lattice. We find explicit analytical formulas for the sum of
      all paths for arbitrary leaf separation r as well as the average distances and
      the moments thereof. We show that the resulting explicit expressions can be
      recast in terms of Hurwitz-Lerch transcendants. Results for periodic trees are
      also given. For incomplete random binary trees, we provide first results by
      numerical techniques; we find a rapid drop of leaf-to-leaf distances for large r.

PMID- 25974465
TI  - Second virial coefficient of rod-shaped molecules and molecular dynamics
      simulations of the isotropic phase.
AB  - The second virial coefficient, B(2) is computed of linear rigid rods composed of
      m equally spaced sites interacting with sites on other rods via the hard-sphere
      or Weeks-Chandler-Andersen (WCA) pair potentials. The dependence of B(2) on a
      wide range of separation distance between the sites L and m for both types of
      potential is computed. Molecular dynamics simulations were carried out of the
      thermodynamic, static, and percolation properties of the WCA rigid rods in the
      isotropic phase as a function of rod number density rho. Simple scaling
      relationships are discovered between thermodynamic and other static properties as
      a function of rho and m, which extend well into the semidilute density range. The
      percolation threshold distance (PTD) between the centers of mass of the rods
      complies well with a mean-field random orientation approximation from low density
      well into the semidilute regime. The corresponding site-site PTD proved more
      problematic to represent by simple functions, but at high rod density, scales
      better with the number of sites density rather than the rod number density.

PMID- 25974466
TI  - Inducing dynamical bistability by reversible compression of an optical piston.
AB  - We study the reversible crossover between stable and bistable phases of an
      overdamped Brownian bead inside an optical piston. The interaction potentials are
      solved developing a method based on Kramers's theory that exploits the
      statistical properties of the stochastic motion of the bead. We evaluate
      precisely the energy balance of the crossover. We show that the deformation of
      the optical potentials induced by the compression of the piston is related to a
      production of heat balanced between potential energy changes and the total amount
      of work performed by the piston. This reveals how specific thermodynamic
      processes can be designed and controlled with a high level of precision by
      tailoring the optical landscapes of the piston. 

PMID- 25974467
TI  - Statistical mechanics of random geometric graphs: Geometry-induced first-order
      phase transition.
AB  - Random geometric graphs (RGGs) can be formalized as hidden-variables models where
      the hidden variables are the coordinates of the nodes. Here we develop a general
      approach to extract the typical configurations of a generic hidden-variables
      model and apply the resulting equations to RGGs. For any RGG, defined through a
      rigid or a soft geometric rule, the method reduces to a nontrivial satisfaction
      problem: Given N nodes, a domain D, and a desired average connectivity <k>, find,
      if any, the distribution of nodes having support in D and average connectivity
      <k>. We find out that, in the thermodynamic limit, nodes are either uniformly
      distributed or highly condensed in a small region, the two regimes being
      separated by a first-order phase transition characterized by a O(N) jump of <k>.
      Other intermediate values of <k> correspond to very rare graph realizations. The
      phase transition is observed as a function of a parameter a?[0,1] that tunes the
      underlying geometry. In particular, a=1 indicates a rigid geometry where only
      close nodes are connected, while a=0 indicates a rigid antigeometry where only
      distant nodes are connected. Consistently, when a=1/2 there is no geometry and no
      phase transition. After discussing the numerical analysis, we provide a
      combinatorial argument to fully explain the mechanism inducing this phase
      transition and recognize it as an easy-hard-easy transition. Our result shows
      that, in general, ad hoc optimized networks can hardly be designed, unless to
      rely to specific heterogeneous constructions, not necessarily scale free. 

PMID- 25974468
TI  - Statistical theory of designed quantum transport across disordered networks.
AB  - We explain how centrosymmetry, together with a dominant doublet of energy
      eigenstates in the local density of states, can guarantee interference-assisted,
      strongly enhanced, strictly coherent quantum excitation transport between two
      predefined sites of a random network of two-level systems. Starting from a
      generalization of the chaos-assisted tunnelling mechanism, we formulate a random
      matrix theoretical framework for the analytical prediction of the transfer time
      distribution, of lower bounds of the transfer efficiency, and of the scaling
      behavior of characteristic statistical properties with the size of the network.
      We show that these analytical predictions compare well to numerical simulations,
      using Hamiltonians sampled from the Gaussian orthogonal ensemble. 

PMID- 25974469
TI  - Essential equivalence of the general equation for the nonequilibrium reversible
      irreversible coupling (GENERIC) and steepest-entropy-ascent models of dissipation
      for nonequilibrium thermodynamics.
AB  - By reformulating the steepest-entropy-ascent (SEA) dynamical model for
      nonequilibrium thermodynamics in the mathematical language of differential
      geometry, we compare it with the primitive formulation of the general equation
      for the nonequilibrium reversible-irreversible coupling (GENERIC) model and
      discuss the main technical differences of the two approaches. In both dynamical
      models the description of dissipation is of the "entropy-gradient" type. SEA
      focuses only on the dissipative, i.e., entropy generating, component of the time
      evolution, chooses a sub-Riemannian metric tensor as dissipative structure, and
      uses the local entropy density field as potential. GENERIC emphasizes the
      coupling between the dissipative and nondissipative components of the time
      evolution, chooses two compatible degenerate structures (Poisson and degenerate
      co-Riemannian), and uses the global energy and entropy functionals as potentials.
      As an illustration, we rewrite the known GENERIC formulation of the Boltzmann
      equation in terms of the square root of the distribution function adopted by the
      SEA formulation. We then provide a formal proof that in more general frameworks,
      whenever all degeneracies in the GENERIC framework are related to conservation
      laws, the SEA and GENERIC models of the dissipative component of the dynamics are
      essentially interchangeable, provided of course they assume the same kinematics.
      As part of the discussion, we note that equipping the dissipative structure of
      GENERIC with the Leibniz identity makes it automatically SEA on metric leaves. 

PMID- 25974470
TI  - Nonlinear Ehrenfest's urn model.
AB  - Ehrenfest's urn model is modified by introducing nonlinear terms in the
      associated transition probabilities. It is shown that these modifications lead,
      in the continuous limit, to a Fokker-Planck equation characterized by two
      competing diffusion terms, namely, the usual linear one and a nonlinear diffusion
      term typical of anomalous diffusion. By considering a generalized H theorem, the
      associated entropy is calculated, resulting in a sum of Boltzmann-Gibbs and
      Tsallis entropic forms. It is shown that the stationary state of the associated
      Fokker-Planck equation satisfies precisely the same equation obtained by
      extremization of the entropy. Moreover, the effects of the nonlinear
      contributions on the entropy production phenomenon are also analyzed. 

PMID- 25974471
TI  - Stochastic approach to equilibrium and nonequilibrium thermodynamics.
AB  - We develop the stochastic approach to thermodynamics based on stochastic
      dynamics, which can be discrete (master equation) and continuous (Fokker-Planck
      equation), and on two assumptions concerning entropy. The first is the definition
      of entropy itself and the second the definition of entropy production rate, which
      is non-negative and vanishes in thermodynamic equilibrium. Based on these
      assumptions, we study interacting systems with many degrees of freedom in
      equilibrium or out of thermodynamic equilibrium and how the macroscopic laws are
      derived from the stochastic dynamics. These studies include the quasiequilibrium
      processes; the convexity of the equilibrium surface; the monotonic time behavior
      of thermodynamic potentials, including entropy; the bilinear form of the entropy
      production rate; the Onsager coefficients and reciprocal relations; and the
      nonequilibrium steady states of chemical reactions. 

PMID- 25974472
TI  - Degenerate optimal paths in thermally isolated systems.
AB  - We present an analysis of the work performed on a system of interest that is kept
      thermally isolated during the switching of a control parameter. We show that
      there exists, for a certain class of systems, a finite-time family of switching
      protocols for which the work is equal to the quasistatic value. These optimal
      paths are obtained within linear response for systems initially prepared in a
      canonical distribution. According to our approach, such protocols are composed of
      a linear part plus a function which is odd with respect to time reversal. For
      systems with one degree of freedom, we claim that these optimal paths may also
      lead to the conservation of the corresponding adiabatic invariant. This points to
      an interesting connection between work and the conservation of the volume
      enclosed by the energy shell. To illustrate our findings, we solve analytically
      the harmonic oscillator and present numerical results for certain anharmonic
      examples. 

PMID- 25974473
TI  - Linear processes in high dimensions: Phase space and critical properties.
AB  - In this work we investigate the generic properties of a stochastic linear model
      in the regime of high dimensionality. We consider in particular the vector
      autoregressive (VAR) model and the multivariate Hawkes process. We analyze both
      deterministic and random versions of these models, showing the existence of a
      stable phase and an unstable phase. We find that along the transition region
      separating the two regimes the correlations of the process decay slowly, and we
      characterize the conditions under which these slow correlations are expected to
      become power laws. We check our findings with numerical simulations showing
      remarkable agreement with our predictions. We finally argue that real systems
      with a strong degree of self-interaction are naturally characterized by this type
      of slow relaxation of the correlations. 

PMID- 25974474
TI  - Diffusive mixing and Tsallis entropy.
AB  - Brownian motion, the classical diffusive process, maximizes the Boltzmann-Gibbs
      entropy. The Tsallis q entropy, which is nonadditive, was developed as an
      alternative to the classical entropy for systems which are nonergodic. A
      generalization of Brownian motion is provided that maximizes the Tsallis entropy
      rather than the Boltzmann-Gibbs entropy. This process is driven by a Brownian
      measure with a random diffusion coefficient. The distribution of this coefficient
      is derived as a function of q for 1<q<3. Applications to transport in porous
      media are considered. 

PMID- 25974475
TI  - Nash equilibrium and evolutionary dynamics in semifinalists' dilemma.
AB  - We consider a tournament among four equally strong semifinalists. The players
      have to decide how much stamina to use in the semifinals, provided that the rest
      is available in the final and the third-place playoff. We investigate optimal
      strategies for allocating stamina to the successive matches when players' prizes
      (payoffs) are given according to the tournament results. From the basic
      assumption that the probability to win a match follows a nondecreasing function
      of stamina difference, we present symmetric Nash equilibria for general payoff
      structures. We find three different phases of the Nash equilibria in the payoff
      space. First, when the champion wins a much bigger payoff than the others, any
      pure strategy can constitute a Nash equilibrium as long as all four players adopt
      it in common. Second, when the first two places are much more valuable than the
      other two, the only Nash equilibrium is such that everyone uses a pure strategy
      investing all stamina in the semifinal. Third, when the payoff for last place is
      much smaller than the others, a Nash equilibrium is formed when every player
      adopts a mixed strategy of using all or none of its stamina in the semifinals. In
      a limiting case that only last place pays the penalty, this mixed-strategy
      profile can be proved to be a unique symmetric Nash equilibrium, at least when
      the winning probability follows a Heaviside step function. Moreover, by using
      this Heaviside step function, we study the tournament by using evolutionary
      replicator dynamics to obtain analytic solutions, which reproduces the
      corresponding Nash equilibria on the population level and gives information on
      dynamic aspects. 

PMID- 25974476
TI  - Effect of interference between two colored noises on the stationary states of a
      Brownian particle.
AB  - In this paper we present properties of an external colored cross-correlated noise
      driven Brownian system which is coupled to a thermal bath. Multiplicative cross
      correlated noises can stabilize the transition state. Thus by monitoring the
      interference between the noises one can understand the mechanism of a chemical
      reaction. At the same time, we have investigated how the interference affects the
      barrier-crossing dynamics. In its presence breakdown of the Arrhenius result
      occurs. The breakdown becomes prominent if the multiplicative noises become
      additive in nature. We have also investigated how the power law behavior of the
      rate constant as a function of damping strength is affected by the properties of
      external colored noises. Furthermore, we have observed that multiplicative
      colored cross-correlated noises can induce the resonant activation phenomenon. 

PMID- 25974477
TI  - Thermal and structural properties of ionic fluids.
AB  - The electrostatic interaction in ionic fluids is well known to give rise to a
      characteristic phase behavior and structure. Sometimes its long range is proposed
      to single out the electrostatic potential over other interactions with shorter
      ranges. Here the importance of the range for the phase behavior and the structure
      of ionic fluids is investigated by means of grandcanonical Monte Carlo
      simulations of the lattice restricted primitive model (LRPM). The long-ranged
      electrostatic interaction is compared to various types of short-ranged potentials
      obtained by sharp and/or smooth cutoff schemes. Sharply cutoff electrostatic
      potentials are found to lead to a strong dependence of the phase behavior and the
      structure on the cutoff radius. However, when combined with a suitable additional
      smooth cutoff, the short-ranged LRPM is found to exhibit quantitatively the same
      phase behavior and structure as the conventional long-ranged LRPM. Moreover, the
      Stillinger-Lovett perfect screening property, which is well known to be generated
      by the long-ranged electrostatic potential, is also fulfilled by short-ranged
      LRPMs with smooth cutoffs. By showing that the characteristic phase behavior and
      structure of ionic fluids can also be found in systems with short-ranged
      potentials, one can conclude that the decisive property of the electrostatic
      potential in ionic fluids is not the long range but rather the valency
      dependence. 

PMID- 25974478
TI  - Shear-induced rigidity in athermal materials: A unified statistical framework.
AB  - Recent studies of athermal systems such as dry grains and dense, non-Brownian
      suspensions have shown that shear can lead to solidification through the process
      of shear jamming in grains and discontinuous shear thickening in suspensions. The
      similarities observed between these two distinct phenomena suggest that the
      physical processes leading to shear-induced rigidity in athermal materials are
      universal. We present a nonequilibrium statistical mechanics model, which
      exhibits the phenomenology of these shear-driven transitions, shear jamming and
      discontinuous shear thickening, in different regions of the predicted phase
      diagram. Our analysis identifies the crucial physical processes underlying shear
      driven rigidity transitions, and clarifies the distinct roles played by shearing
      forces and the packing fraction of grains. 

PMID- 25974479
TI  - From the granular Leidenfrost state to buoyancy-driven convection.
AB  - Grains inside a vertically vibrated box undergo a transition from a density
      inverted and horizontally homogeneous state, referred to as the granular
      Leidenfrost state, to a buoyancy-driven convective state. We perform a
      simulational study of the precursors of such a transition and quantify their
      dynamics as the bed of grains is progressively fluidized. The transition is
      preceded by transient convective states, which increase their correlation time as
      the transition point is approached. Increasingly correlated convective flows lead
      to density fluctuations, as quantified by the structure factor, that also shows
      critical behavior near the transition point. The amplitude of the modulations in
      the vertical velocity field are seen to be best described by a quintic
      supercritical amplitude equation with an additive noise term. The validity of
      such an amplitude equation, and previously observed collective semiperiodic
      oscillations of the bed of grains, suggests a new interpretation of the
      transition analogous to a coupled chain of vertically vibrated damped
      oscillators. Increasing the size of the container shows metastability of
      convective states, as well as an overall invariant critical behavior close to the
      transition. 

PMID- 25974480
TI  - Cluster and constraint analysis in tetrahedron packings.
AB  - The disordered packings of tetrahedra often show no obvious macroscopic
      orientational or positional order for a wide range of packing densities, and it
      has been found that the local order in particle clusters is the main order form
      of tetrahedron packings. Therefore, a cluster analysis is carried out to
      investigate the local structures and properties of tetrahedron packings in this
      work. We obtain a cluster distribution of differently sized clusters, and peaks
      are observed at two special clusters, i.e., dimer and wagon wheel. We then
      calculate the amounts of dimers and wagon wheels, which are observed to have
      linear or approximate linear correlations with packing density. Following our
      previous work, the amount of particles participating in dimers is used as an
      order metric to evaluate the order degree of the hierarchical packing structure
      of tetrahedra, and an order map is consequently depicted. Furthermore, a
      constraint analysis is performed to determine the isostatic or hyperstatic region
      in the order map. We employ a Monte Carlo algorithm to test jamming and then
      suggest a new maximally random jammed packing of hard tetrahedra from the order
      map with a packing density of 0.6337. 

PMID- 25974481
TI  - Role of contact-angle hysteresis for fluid transport in wet granular matter.
AB  - The stability of sand castles is determined by the structure of wet granulates.
      Experimental data on the size distribution of fluid pockets are ambiguous with
      regard to their origin. We discovered that contact-angle hysteresis plays a
      fundamental role in the equilibrium distribution of bridge volumes, and not
      geometrical disorder as commonly conjectured. This has substantial consequences
      on the mechanical properties of wet granular beds, including a history-dependent
      rheology and lowered strength. Our findings are obtained using a model in which
      the Laplace pressures, bridge volumes, and contact angles are dynamical variables
      associated with the contact points. While accounting for contact line pinning, we
      track the temporal evolution of each bridge. We observe a crossover to a power
      law decay of the variance of capillary pressures at late times and a saturation
      of the variance of bridge volumes to a finite value connected to contact line
      pinning. Large-scale simulations of liquid transport in the bridge network reveal
      that the equilibration dynamics at early times is well described by a mean-field
      model. The spread of final bridge volumes can be directly related to the
      magnitude of contact-angle hysteresis. 

PMID- 25974482
TI  - Compaction of highly porous granular matter by impacts on a hard wall.
AB  - Using a granular-mechanics code, we study the impact of a highly porous granular
      body on a hard wall. The projectile consists of monodisperse adhesive micrometer
      sized silica grains. For the impact velocities studied, v<0.5m/s, the sample does
      not fragment, but is compacted. We find that the compaction is proportional to
      the impact speed. The proportionality constant increases with decreasing
      porosity. However, the compaction is inhomogeneous and decreases with distance
      from the target. A compaction wave runs through the aggregate; it slows down
      while the compaction becomes less efficient. 

PMID- 25974484
TI  - Granular chains with soft boundaries: Slowing the transition to quasiequilibrium.
AB  - We present here a detailed numerical study of the dynamical behavior of "soft"
      uncompressed grains in a granular chain where the grains interact via the
      intrinsically nonlinear Hertz force. It is well known that such a chain supports
      the formation of solitary waves (SWs). Here, however, the system response to the
      material properties of the grains and boundaries is explored further. In
      particular, we examine the details of the transition of the system from a SW
      phase to an equilibrium-like (or quasiequilibrium) phase, and for this reason we
      ignore the effects of dissipation in this study. We find that the soft walls slow
      the reflection of SWs at the boundaries of the system, which in turn slows the
      journey to quasiequilibrium. Moreover, the increased grain-wall compression as
      the boundaries are softened results in fewer average grain-grain contacts at any
      given time in the quasiequilibrium phase. These effects lead to increased kinetic
      energy fluctuations in the short term in softer systems. We conclude with a toy
      model that exploits the results of soft-wall systems. This toy model supports the
      formation of breather-like entities and may therefore be useful for localizing
      energy in desired places in the granular chain. 

PMID- 25974483
TI  - Avalanche dynamics of granular materials under the slumping regime in a rotating
      drum as revealed by speckle visibility spectroscopy.
AB  - We used speckle visibility spectroscopy to measure the time-resolved dynamcis of
      avalanching down the inclined surface of a granular material in a half-full
      rotating drum operating in the slumping regime. The distribution of the avalanche
      period, t(d), rest time between them, t(r), and peak particle velocity
      fluctuation, deltav(p)(2), are all normally distributed. While the distributions
      of the two times at the top and bottom of the free surface are very similar, the
      particle velocity fluctuation is greater at the bottom of the free surface than
      at the top. The rest time is observed to be inversely related to the drum speed.
      Combining this with the relation of t(r) and the difference of the upper and
      lower angle of repose for the granular material, Deltatheta, we find that the
      latter decreases linearly with increasing rotational speed. We also observe that
      t(d) increases in a linear fashion with the drum speed. Using the relation of
      t(r) and the distance that particles have to move during an avalanche, we further
      find that a new scaling relation of the mean number of avalanches required to
      traverse the free surface with drum speed. We find that the slumping frequency
      increases with the rotating speed before becoming constant in the slumping-to
      rolling transition region. Finally, we find that the average peak of the
      fluctuation speed of the avalanche, deltav(p)(2), increases linearly with the
      drum speed.

PMID- 25974485
TI  - Electrical conductivity of quasi-two-dimensional foams.
AB  - Quasi-two-dimensional (quasi-2D) foams consist of monolayers of bubbles squeezed
      between two narrowly spaced plates. These simplified foams have served
      successfully in the past to shed light on numerous issues in foam physics. Here
      we consider the electrical conductivity of such model foams. We compare
      experiments to a model which we propose, and which successfully relates the
      structural and the conductive properties of the foam over the full range of the
      investigated liquid content. We show in particular that in the case of quasi-2D
      foams the liquid in the nodes needs to be taken into account even at low liquid
      content. We think that these results may provide different approaches for the
      characterization of foam properties and for the in situ characterization of the
      liquid content of foams in confining geometries, such as microfluidics. 

PMID- 25974486
TI  - Aging and crystallization in a lattice glass model.
AB  - We have studied the three-dimensional lattice glass of Pica Ciamarra et al.
      [Phys. Rev. E 67, 057105 (2003)], which has been shown to reproduce several
      features of the structural glass phenomenology, such as the cage effect,
      exponential increase of relaxation times, and aging. We show, using short-time
      dynamics, that the metastability limit is above the estimated Kauzmann
      temperature. We also find that in the region where the metastable liquid exists
      the aging exponent is lower than 0.5, indicating that equilibrium is reached
      relatively quickly. We conclude that the usefulness of this model to study the
      deeply supercooled regime is rather limited.

PMID- 25974487
TI  - Two spheres translating in tandem through a colloidal suspension.
AB  - Using laser tweezers, two colloidal particles are held parallel to a uniformly
      flowing suspension of similarly sized bath particles at an effective volume
      fraction phi(eff)=0.41. The local deformation in the bath suspension is imaged by
      confocal microscopy, and, concurrently, the drag forces exerted on both the
      leading and the trailing probe particles are measured as a function of probe
      separation and velocity. The bath structure changes in response to the velocity
      and separation of the probes. A depleted region between probes is observed at
      sufficiently high velocities. Both probes experience the same drag force and the
      drag force increases with probe separation. The results indicate that bath-probe
      and probe-probe hydrodynamic interactions contribute microstructure and drag
      force and that drag exerted by direct bath-probe collisions is reduced compared
      to an isolated probe.

PMID- 25974488
TI  - Three-body critical Casimir forces.
AB  - Within mean-field theory we calculate universal scaling functions associated with
      critical Casimir forces for a system consisting of three parallel cylindrical
      colloids immersed in a near-critical binary liquid mixture. For several
      geometrical arrangements and boundary conditions at the surfaces of the colloids
      we study the force between two colloidal particles in the direction normal to
      their axes, analyzing the influence of the presence of a third particle on that
      force. Upon changing temperature or the relative positions of the particles we
      observe interesting features such as a change of sign of this force caused by the
      presence of the third particle. We determine the three-body component of the
      forces acting on one of the colloids by subtracting the pairwise forces from the
      total force. The three-body contribution to the total critical Casimir force
      turns out to be more pronounced for small surface-to-surface distances between
      the colloids as well as for temperatures close to criticality. Moreover, we
      compare our results with similar ones for other physical systems such as three
      atoms interacting via van der Waals forces. 

PMID- 25974489
TI  - Two-step build-up of a thermoreversible polymer network: From early local to late
      collective dynamics.
AB  - We probe the mechanisms at work in the build-up of thermoreversible gel networks,
      with the help of hybrid gelatin gels containing a controlled density of
      irreversible, covalent crosslinks (CLs), which we quench below the physical
      gelation temperature. The detailed analysis of the dependence on covalent
      crosslink density of both the shear modulus and optical activity evolutions with
      time after quench enables us to identify two stages of the physical gelation
      process, separated by a temperature-dependent crossover modulus: (i) an early
      nucleation regime during which rearrangements of the triple-helix CLs play a
      negligible role, and (ii) a late, logarithmic aging one, which is preserved,
      though slowed down, in the presence of irreversible CLs. We show that aging is
      fully controlled by rearrangements and discuss the implication of our results in
      terms of the switch from an early, local dynamics to a late, cooperative long
      range one. 

PMID- 25974490
TI  - Colloidal dynamics over a tilted periodic potential: Nonequilibrium steady-state
      distributions.
AB  - We report a systematic study of the effects of the external force F on the
      nonequilibrium steady-state (NESS) dynamics of the diffusing particles over a
      tilted periodic potential, in which detailed balance is broken due to the
      presence of a steady particle flux. A tilted two-layer colloidal system is
      constructed for this study. The periodic potential is provided by the bottom
      layer colloidal spheres forming a fixed crystalline pattern on a glass substrate.
      The corrugated surface of the bottom colloidal crystal provides a gravitational
      potential field for the top-layer diffusing particles. By tilting the sample at
      an angle theta with respect to the vertical (gravity) direction, a tangential
      component of the gravitational force F is applied to the diffusing particles. The
      measured NESS probability density function P(ss)(x,y) of the particles is found
      to deviate from the equilibrium distribution P(x,y) to a different extent,
      depending on the driving or distance from equilibrium. The experimental results
      are compared with the exact solution of the one-dimensional (1D) Smoluchowski
      equation and the numerical results of the 2D Smoluchowski equation. From the
      obtained exact solution of the 1D Smoluchowski equation, we develop an analytical
      method to accurately extract the 1D potential U(0)(x) from the measured P(ss)(x).
      This work demonstrates that the tilted periodic potential provides a useful
      platform for the study of forced barrier-crossing dynamics beyond the Arrhenius
      Kramers equation.

PMID- 25974491
TI  - Effects of finite ionic size and solvent polarization on the dynamics of
      electrolytes probed through harmonic disturbances.
AB  - We address the implications of finite ionic size and solvent polarization on the
      response of the electric double layer (EDL) at two cation-selective electrodes in
      nonequilibrium conditions. The current between the electrodes is driven by a
      steady-state dc bias in conjunction with a probing high-frequency ac voltage. We
      report that the finite ionic size (steric) effect is prominent at high voltages
      near the electrodes where the ion densities are high, while the solvent
      polarization dramatically alters impedance characteristics for thick EDLs owing
      to the alteration of solvent permittivity in regions with a high electric field.
      Depending on the magnitude of the dc bias, our results show that the steric
      effects and solvent polarization lead to dramatic alterations in the net
      impedance for moderately thick electric double layers as compared to an extremely
      thin one. We also highlight that the solvent polarization suppresses the
      anomalous growth of dc current (anomalous rectification effect) for applied high
      frequency ac voltages. 

PMID- 25974492
TI  - Principal-component analysis of particle motion.
AB  - We demonstrate the application of principal-component analysis (PCA) to the
      analysis of particle motion data in the form of a time series of images. PCA has
      the ability to resolve and isolate spatiotemporal patterns in the data. Using
      simulated data, we show that this translates into the ability to separate
      individual frequency components of the particle motion. We also show that PCA can
      be used to extract the fluid viscosity from images of particles undergoing
      Brownian motion. PCA thus provides an efficient alternative to more traditional
      particle-tracking methods for the analysis of microrheological data. 

PMID- 25974493
TI  - Correlated heterogeneous dynamics in glass-forming polymers.
AB  - We report x-ray photon correlation spectroscopy experiments on the dynamics of
      the glass-former polypropylene glycol covering a temperature range from room
      temperature to the glass transition at T(g)=205 K using silica tracer particles.
      Three temperature regimes are identified: At high temperatures, Brownian motion
      of the tracer particles is observed. Near T(g), the dynamics is hyperdiffusive
      and ballistic. Around 1.12T(g), we observe an intermediate regime. Here the
      stretching exponent of the Kohlrausch-Williams-Watts function becomes q
      dependent. By analyzing higher-order correlations in the scattering data, we find
      that dynamical heterogeneities dramatically increase in this intermediate
      temperature regime. This leads to two effects: increasing heterogeneous dynamics
      and correlated motion at temperatures close to and below 1.12T(g).

PMID- 25974494
TI  - Effective interactions in active Brownian suspensions.
AB  - Active colloids exhibit persistent motion, which can lead to motility-induced
      phase separation (MIPS). However, there currently exists no microscopic theory to
      account for this phenomenon. We report a first-principles theory, free of fit
      parameters, for active spherical colloids, which shows explicitly how an
      effective many-body interaction potential is generated by activity and how this
      can rationalize MIPS. For a passively repulsive system the theory predicts phase
      separation and pair correlations in quantitative agreement with simulation. For
      an attractive system the theory shows that phase separation becomes suppressed by
      moderate activity, consistent with recent experiments and simulations, and
      suggests a mechanism for reentrant cluster formation at high activity. 

PMID- 25974495
TI  - Sound propagation in liquid foams: Unraveling the balance between physical and
      chemical parameters.
AB  - We present experimental results on the propagation of an ultrasonic wave (40 kHz)
      in liquid foams, as a function of the foam physical and chemical parameters. We
      have first implemented an original setup, using transducers in a transmission
      configuration. The foam coarsening was used to vary the bubble size (remaining in
      the submillimeter range), and we have made foams with various chemical
      formulations, to investigate the role of the chemicals at the bubble interfaces
      or in bulk. The results are compared with recently published theoretical works,
      and good agreements are found. In particular, for all the foams, we have
      evidenced two asymptotic limits, at small and large bubble size, connected by a
      nontrivial resonant behavior, associated to an effective negative density. These
      qualitative features are robust whatever the chemical formulation; we discuss the
      observed differences between the samples, in relation to the interfacial and bulk
      viscoelasticity. These results demonstrate the rich and complex acoustic behavior
      of foams. While the bubble size remain here always smaller than the sound
      wavelength, it turns out that one must go well beyond mean-field modeling to
      describe the foam acoustic properties. 

PMID- 25974496
TI  - Origin and detection of microstructural clustering in fluids with spatial-range
      competitive interactions.
AB  - Fluids with competing short-range attractions and long-range repulsions mimic
      dispersions of charge-stabilized colloids that can display equilibrium structures
      with intermediate-range order (IRO), including particle clusters. Using
      simulations and analytical theory, we demonstrate how to detect cluster formation
      in such systems from the static structure factor and elucidate links to
      macrophase separation in purely attractive reference fluids. We find that
      clusters emerge when the thermal correlation length encoded in the IRO peak of
      the structure factor exceeds the characteristic length scale of interparticle
      repulsions. We also identify qualitative differences between the dynamics of
      systems that form amorphous versus microcrystalline clusters. 

PMID- 25974497
TI  - Dimensional study of the dynamical arrest in a random Lorentz gas.
AB  - The random Lorentz gas (RLG) is a minimal model for transport in heterogeneous
      media. Upon increasing the obstacle density, it exhibits a growing subdiffusive
      transport regime and then a dynamical arrest. Here, we study the dimensional
      dependence of the dynamical arrest, which can be mapped onto the void percolation
      transition for Poisson-distributed point obstacles. We numerically determine the
      arrest in dimensions d=2-6. Comparison of the results with standard mode-coupling
      theory reveals that the dynamical theory prediction grows increasingly worse with
      d. In an effort to clarify the origin of this discrepancy, we relate the
      dynamical arrest in the RLG to the dynamic glass transition of the infinite-range
      Mari-Kurchan-model glass former. Through a mixed static and dynamical analysis,
      we then extract an improved dimensional scaling form as well as a geometrical
      upper bound for the arrest. The results suggest that understanding the asymptotic
      behavior of the random Lorentz gas may be key to surmounting fundamental
      difficulties with the mode-coupling theory of glasses. 

PMID- 25974498
TI  - Dynamic hysteresis in the rheology of complex fluids.
AB  - Recently, rheological hysteresis has been studied systematically in a wide range
      of complex fluids combining global rheology and time-resolved velocimetry. In
      this paper we present an analysis of the roles of the three most fundamental
      mechanisms in simple-yield-stress fluids: structure dynamics, viscoelastic
      response, and spatial flow heterogeneities, i.e., time-dependent shear bands.
      Dynamical hysteresis simulations are done analogously to rheological ramp-up and 
      down experiments on a coupled model which incorporates viscoelasticity and time
      dependent structure evolution. Based on experimental data, a coupling between
      hysteresis measured from the local velocity profiles and that measured from the
      global flow curve has been suggested. According to the present model, even if
      transient shear banding appears during the shear ramps, in typical narrow-gap
      devices, only a small part of the hysteretic response can be attributed to
      heterogeneous flow. This results in decoupling of the hysteresis measured from
      the local velocity profiles and the global flow curve, demonstrating that for an
      arbitrary time-dependent rheological response this proposed coupling can be very
      weak. 

PMID- 25974499
TI  - Scaled-particle theory analysis of cylindrical cavities in solution.
AB  - The solvation of hard spherocylindrical solutes is analyzed within the context of
      scaled-particle theory, which takes the view that the free energy of solvating an
      empty cavitylike solute is equal to the pressure-volume work required to inflate
      a solute from nothing to the desired size and shape within the solvent. Based on
      our analysis, an end cap approximation is proposed to predict the solvation free
      energy as a function of the spherocylinder length from knowledge regarding only
      the solvent density in contact with a spherical solute. The framework developed
      is applied to extend Reiss's classic implementation of scaled-particle theory and
      a previously developed revised scaled-particle theory to spherocylindrical
      solutes. To test the theoretical descriptions developed, molecular simulations of
      the solvation of infinitely long cylindrical solutes are performed. In hard
      sphere solvents classic scaled-particle theory is shown to provide a reasonably
      accurate description of the solvent contact correlation and resulting solvation
      free energy per unit length of cylinders, while the revised scaled-particle
      theory fitted to measured values of the contact correlation provides a
      quantitative free energy. Applied to the Lennard-Jones solvent at a state-point
      along the liquid-vapor coexistence curve, however, classic scaled-particle theory
      fails to correctly capture the dependence of the contact correlation. Revised
      scaled-particle theory, on the other hand, provides a quantitative description of
      cylinder solvation in the Lennard-Jones solvent with a fitted interfacial free
      energy in good agreement with that determined for purely spherical solutes. The
      breakdown of classical scaled-particle theory does not result from the failure of
      the end cap approximation, however, but is indicative of neglected higher-order
      curvature dependences on the solvation free energy. 

PMID- 25974500
TI  - Micrometer-scale electrical breakdown in high-density fluids with large density
      fluctuations: Numerical model and experimental assessment.
AB  - Experimentally observed electrical breakdown voltages (U(B)) in high-pressure
      gases and supercritical fluids deviate from classical theories for low-pressure
      gas discharges, and the underlying breakdown mechanisms for the high-density
      fluids making the U(B) differ from those in the classical discharges are not yet
      well understood. In this study, we developed an electrical breakdown model for
      the high-density fluids taking into account the effects of density fluctuations
      and ion-enhanced field emission (IEFE). The model is based on the concept that a
      critical anomaly of the U(B) (local minimum near the critical point) is caused by
      long mean free electron path leading to a large first Townsend coefficient in
      locally low-density spatial domains generated by the density fluctuations. Also,
      a modified Paschen's curve considering the effect of the IEFE on the second
      Townsend coefficient was used to reproduce the U(B) curve in the high-density
      fluids. Calculations based on the novel model showed good agreements with the
      experimentally measured U(B) even near the critical point and it also suggested
      that the critical anomaly of the U(B) depends on the gap distance. These results
      indicate that both the density fluctuations and the IEFE have to be considered to
      comprehend the plasmas in high-density and density-fluctuating fluids.

PMID- 25974501
TI  - Magnetic and structural study of electric double-layered ferrofluid with
      MnFe(2)O(4)@gamma-Fe(2)O(3) nanoparticles of different mean diameters:
      Determination of the magnetic correlation distance.
AB  - Magnetic fluids based on manganese ferrite nanoparticles were studied from the
      structural point of view through small angle x-rays scattering (SAXS) and from
      the magnetic point of view through zero-field cooling and field cooling (ZFC-FC)
      and ac susceptibility measurements (MS). Three different colloids with particles
      mean diameters of 2.78,3.42, and 6.15 nm were investigated. The size distribution
      obtained from SAXS measurements follows a log-normal behavior. The ZFC-FC and MS
      results revealed the presence of an important magnetic interaction between the
      nanoparticles, characterized by a magnetic correlation distance Lambda. The
      colloidal medium can be pictures as composed by magnetic cluster constituted by N
      interacting particles. These magnetic clusters are not characterized by a
      physical aggregation of particles. The energy barrier energy obtained is
      consistent with the existence of this magnetic clusters. Besides the magnetic
      interaction between particles, confinement effects must be included to account
      for the experimental values of the magnetic energy barrier encountered. 

PMID- 25974502
TI  - Effect of bending stiffness on the peeling behavior of an elastic thin film on a
      rigid substrate.
AB  - Inspired by the experimental observation that the maximum peeling force of
      elastic films on rigid substrates does not always emerge at the steady-state
      peeling stage, but sometimes at the initial one, a theoretical model is
      established in this paper, in which not only the effect of the film's bending
      stiffness on the peeling force is considered, but also the whole peeling process,
      from the initiation of debonding to the steady-state stage, is characterized.
      Typical peeling force-displacement curves and deformed profiles of the film
      reappear for the whole peeling process. For the case of a film with relatively
      large bending stiffness, the maximum peeling force is found arising at the
      initial peeling stage and the larger the stiffness of the film, the larger the
      maximum peeling force is. With the peeling distance increasing, the peeling force
      is reduced from the maximum to a constant at the steady-state stage. For the case
      of a film with relatively small stiffness, the peeling force increases
      monotonically at the initial stage and then achieves a constant as the maximum at
      the steady-state stage. Furthermore, the peeling forces in the steady-state stage
      are compared with those of the classical Kendall model. All the theoretical
      predictions agree well with the existing experimental and numerical observations,
      from which the maximum peeling force can be predicted precisely no matter what
      the stiffness of the film is. The results in this paper should be very helpful in
      the design and assessment of the film-substrate interface. 

PMID- 25974503
TI  - Undulation amplitude of a fluid membrane surrounded by near-critical binary fluid
      mixtures.
AB  - We consider the thermal undulation, or shape fluctuation, of an almost planar
      fluid membrane surrounded by the same near-critical binary fluid mixtures on both
      sides. A weak preferential attraction is assumed between the membrane and one
      component of the mixture. We use the Gaussian free-energy functional to study the
      equilibrium average of the undulation amplitude within the linear approximation
      with respect to the amplitude. According to our result given by a simple analytic
      formula, the ambient near-criticality tends to suppress the undulation of a
      membrane, and this suppression effect can overwhelm that of the bending rigidity
      for small wave numbers. Thus, the ambient near-criticality is suggested to
      prevent a large membrane from becoming floppy even if the lateral tension
      vanishes at the equilibrium. 

PMID- 25974504
TI  - Slip statistics of dislocation avalanches under different loading modes.
AB  - Slowly compressed microcrystals deform via intermittent slip events, observed as
      displacement jumps or stress drops. Experiments often use one of two loading
      modes: an increasing applied stress (stress driven, soft), or a constant strain
      rate (strain driven, hard). In this work we experimentally test the influence of
      the deformation loading conditions on the scaling behavior of slip events. It is
      found that these common deformation modes strongly affect time series properties,
      but not the scaling behavior of the slip statistics when analyzed with a mean
      field model. With increasing plastic strain, the slip events are found to be
      smaller and more frequent when strain driven, and the slip-size distributions
      obtained for both drives collapse onto the same scaling function with the same
      exponents. The experimental results agree with the predictions of the used mean
      field model, linking the slip behavior under different loading modes. 

PMID- 25974505
TI  - Random sequential adsorption of starlike particles.
AB  - Random packing of surfaceless starlike particles built of 3 to 50 line segments
      was studied using random sequential adsorption algorithm. Numerical simulations
      allow us to determine saturated packing densities as well as the first two virial
      expansion coefficients for such objects. Measured kinetics of the packing growth
      supports the power law known to be valid for particles with a finite surface;
      however, the dependence of the exponent in this law on the number of star arms is
      unexpected. The density autocorrelation function shows fast superexponential
      decay as for disks, but the typical distance between closest stars is much
      smaller than between disks of the similar size, especially for a small number of
      arms. 

PMID- 25974506
TI  - Dynamics driven by lipophilic force in Langmuir monolayers: In-plane and out-of
      plane growth.
AB  - While monolayer area fraction versus time (A(n)-t) curves obtained from surface
      pressure-area (pi-A) isotherms for desorption-dominated (DD) processes in
      Langmuir monolayers of fatty acids represent continuous loss, those from Brewster
      angle microscopy (BAM) also show a two-dimensional (2D) coalescence. For
      nucleation-dominated (ND) processes both techniques suggest competing processes,
      with BAM showing 2D coalescence alongside multilayer formation. pi enhances both
      DD and ND processes with a lower cutoff for ND processes, while temperature has a
      lower cutoff for DD but negligible effect on ND processes. Hydrocarbon chain
      length has the strongest effect, causing a crossover from DD to ND dynamics.
      Imaging ellipsometry of horizontally transferred films onto Si(100) shows
      Stranski-Krastanov-like growth for ND process in an arachidic acid monolayer
      resulting in successive stages of monolayer, trilayer, and multilayer islands,
      ridges from lateral island coalescence, and shallow wavelike structures from
      ridge coalescence on the film surface. These studies show that lipophilic
      attraction between hydrocarbon chains is the driving force at all stages of long
      term monolayer dynamics.

PMID- 25974507
TI  - Theoretical model for fluid-solid coupling in porous materials.
AB  - This paper introduces a unifying theory for describing complex behavior for
      porous materials. The key ingredients are the stored energy in solid-fluid
      interaction as well as the solid-solid and fluid-fluid interactions. A finite
      element formulation is employed which naturally accounts for the pore-pore
      network effects and is easily applicable to most pore geometries such as cellular
      solids and foams. The interactions, built in at the finite element level, give
      rise to the mechanical response of the macroscopic material unit. Through
      numerical studies, we show that there is strong coupling between fluid and solid
      that induces complex mechanical response, i.e., hysteresis and anisotropy. It is
      demonstrated that hysteresis arises directly from the fluid-solid coupling. We
      term this type of hysteresis emergent hysteresis. 

PMID- 25974508
TI  - Water transfer and crack regimes in nanocolloidal gels.
AB  - Direct observations of the surface and shape of model nanocolloidal gels
      associated with measurements of the spatial distribution of water content during
      drying show that air starts to significantly penetrate the sample when the
      material stops shrinking. We show that whether the material fractures or not
      during desiccation, as air penetrates the porous body, the water saturation
      decreases but remains almost homogeneous throughout the sample. This air invasion
      is at the origin of another type of fracture due to capillary effects; these
      results provide insight into the liquid dynamics at the nanoscale. 

PMID- 25974509
TI  - Analytic scaling function for island-size distributions.
AB  - We obtain an explicit solution for the island-size distribution described by the
      rate equations for irreversible growth with the simplified capture rates of the
      form sigma(s)(Theta)?Theta(p)(a+s-1) for all s>=1, where s is the size and Theta
      is the time-dependent coverage. The intrinsic property of this solution is its
      scaling form in the continuum limit. The analytic scaling function depends on the
      two parameters a and p and is capable of describing very dissimilar distribution
      shapes, both monomodal and monotonically decreasing. The obtained results suggest
      that the scaling features of the size distributions are closely related to the
      size linearity of the capture rates. A simple analytic scaling is obtained
      rigorously here and helps to gain a better theoretical understanding of possible
      origins of the scaling behavior of the island-size distributions.

PMID- 25974510
TI  - Unusual polarity-dependent patterns in a bent-core nematic liquid crystal under
      low-frequency ac field.
AB  - Electric-field-induced patterns of diverse morphology have been observed over a
      wide frequency range in a recently synthesized bent-core nematic (BCN) liquid
      crystal. At low frequencies (up to ~25 Hz), the BCN exhibited unusual polarity
      dependent patterns. When the amplitude of the ac field was enhanced, these two
      time-asymmetrical patterns turned into time-symmetrical prewavylike stripes. At
      ac frequencies in the middle-frequency range (~50-3000 Hz), zigzag patterns were
      detected whose obliqueness varied with the frequency. Finally, if the frequency
      was increased above 3 kHz, the zigzag pattern was replaced by another,
      prewavylike pattern, whose threshold voltage depended on the frequency; however,
      the wave vector did not. For a more complete characterization, material
      parameters such as elastic constants, dielectric permittivities, and the
      anisotropy of the diamagnetic susceptibility were also determined. 

PMID- 25974511
TI  - Nematic fluctuations and semisoft elasticity in swollen liquid-crystal
      elastomers.
AB  - Dynamic light scattering (DLS) experiments were performed on stretched sheets of
      liquid crystal elastomers (LCEs) swollen with a nematic solvent with different
      swelling ratios. We show that the obtained stress-strain curve and DLS data can
      still be explained with the concepts of semisoft elasticity. The stress-strain
      curve shows a typical semisoft response with a threshold strain and a plateau
      region where stress increases only a little with the applied strain. The width of
      the plateau decreases with the increase of the swelling ratio because the polymer
      backbone anisotropy reduces during the swelling. The relaxation rate of thermally
      excited director fluctuations, however, still shows a typical response, and our
      measurements indicate the presence of a soft dynamic director-shear mode, as
      predicted by the theory of semisoft elasticity. 

PMID- 25974512
TI  - Light and thermal responses of liquid-crystal-network films: A finite element
      study.
AB  - As a polymeric system incorporating rigid molecules within its structure, the
      liquid-crystal network (LCN) has been envisaged as a novel heterogeneous
      material. Under the influence of external stimuli, the orientational order of the
      liquid-crystalline phase becomes dilute and overall anisotropy is hence
      decreased; the actinic light absorbed by photochromic molecules, for example,
      induces the geometric isomerization and subsequently yields internal stress
      within the local network. In this study we investigate light- and temperature
      induced spontaneous deformations of the LCN structure via a three-dimensional
      finite element model that incorporates geometric nonlinearity with a
      photomechanical constitutive model. We first examine the bending behavior and its
      nonlinearity and then parametrically study the various behaviors that stem from
      different origins ranging from the microscale to the macroscale: (i) the geometry
      of the LCN film, (ii) the macroscopic global order, (iii) the distorted mesogenic
      orientation due to the Fredericks distortion, and (iv) defect-induced
      instability. These interrelated behaviors demonstrate both the simulation
      capability and the necessity of the presenting framework. By employing a
      nonlinear consideration along with a microscopic shape parameter r the present
      approach facilitates further understanding of photomechanical physics such as the
      deconvolution of various stimuli and the deformed shape obtained due to snap
      through instability. Furthermore, this study may offer insight into the design of
      light-sensitive actuation systems by deepening our knowledge and providing an
      efficient measure. 

PMID- 25974513
TI  - Understanding the unusual reorganization of the nanostructure of a dark
      conglomerate phase.
AB  - The dark conglomerate (DC) phase exhibited by a bent-core liquid crystal shows
      remarkable properties including an electric-field tunable chiral domain structure
      and a large (0.045) reduction of refractive index, while maintaining an optically
      dark texture when observed under crossed polarizers. A detailed investigation of
      the system is presented, leading to a model that is fully consistent with the
      experimental observations. It reports the observation of two distinct regimes in
      the DC phase: a higher temperature regime in which the periodicity measured by
      small angle x-ray scattering decreases slightly (0.5%) and a lower temperature
      regime where it increases considerably (16%). Also, the paper discusses the
      unusual electric-field-induced transformations observed in both the regimes.
      These changes have threshold fields that are both temperature and frequency
      dependent, though the phenomena are observed irrespective of device thickness,
      geometry, and the alignment layer. The electro-optic behavior in the DC phase
      corresponds to a number of structural changes leading to unusual changes in
      physical properties including a small (1%) increase in periodicity and a doubling
      of the average dielectric permittivity. We propose a model of the DC phase where
      in the ground state the nanostructure of the phase exhibits an anticlinic
      antiferroelectric organization. Under an electric field, it undergoes a molecular
      rearrangement without any gross structural changes leading to an anticlinic
      ferroelectric order while keeping the overall sponge-like structure of the DC
      phase intact. 

PMID- 25974514
TI  - Surface charge and interactions of 20-nm nanocolloids in a nematic liquid
      crystal.
AB  - We studied real-time motion of individual 20-nm silica nanoparticles in a thin
      layer of a nematic liquid crystal using a dark-field optical videomicroscopy. By
      tracking the positions of individual nanoparticles we observed that particle pair
      interactions are not only mediated by strong thermal fluctuations of the nematic
      liquid crystal, but also with a repulsive force of electric origin. We determined
      the total electric charge of silanated silica particles in the nematic liquid
      crystal 5CB by observing the electric-force-driven drift. Surprisingly, the
      surface electric charge density depends on colloidal size and is ~4.5*10(
      3)C/m(2) for 20-nm nanocolloids, and two orders of magnitude lower, i.e.,
      ~2.3*10(-5)C/m(2), for 1-MUm colloids. We conclude that electrostatic repulsion
      between like-charged particles prevents the formation of permanent colloidal
      assemblies of nanometer size. We also observed strong attraction of 20-nm silica
      nanoparticles to confining polyimide surfaces and larger clusters, which
      gradually results in complete expulsion of nanoparticles from the nematic liquid
      crystal to the surfaces of the confining cell.

PMID- 25974515
TI  - Spatially resolved x-ray studies of liquid crystals with strongly developed bond
      orientational order.
AB  - We present an x-ray study of freely suspended hexatic films of the liquid crystal
      3(10)OBC. Our results reveal spatial inhomogeneities of the bond-orientational
      (BO) order in the vicinity of the hexatic-smectic phase transition and the
      formation of large-scale hexatic domains at lower temperatures. Deep in the
      hexatic phase up to 25 successive sixfold BO order parameters have been directly
      determined by means of angular x-ray cross-correlation analysis (XCCA). Such
      strongly developed hexatic order allowed us to determine higher order correction
      terms in the scaling relation predicted by the multicritical scaling theory over
      a full temperature range of the hexatic phase existence. 

PMID- 25974516
TI  - Experimental realization of crossover in shape and director field of nematic
      tactoids.
AB  - Spindle-shaped nematic droplets (tactoids) form in solutions of rod-like
      molecules at the onset of the liquid crystalline phase. Their unique shape and
      internal structure result from the interplay of the elastic deformation of the
      nematic and anisotropic surface forces. The balance of these forces dictates that
      tactoids must display a continuous variation in aspect ratio and director-field
      configuration. Yet, such continuous transition has eluded observation for
      decades: tactoids have displayed either a bipolar configuration with particles
      aligned parallel to the droplet interface or a homogeneous configuration with
      particles aligned parallel to the long axis of the tactoid. Here, we report the
      first observation of the continuous transition in shape and director-field
      configuration of tactoids in true solutions of carbon nanotubes in chlorosulfonic
      acid. This observation is possible because the exceptional length of carbon
      nanotubes shifts the transition to a size range that can be visualized by optical
      microscopy. Polarization micrographs yield the interfacial and elastic properties
      of the system. Absorbance anisotropy measurements provide the highest nematic
      order parameter (S=0.79) measured to date for a nematic phase of carbon nanotubes
      at coexistence with its isotropic phase. 

PMID- 25974517
TI  - Electric-field-induced flow-aligning state in a nematic liquid crystal.
AB  - The response of shear stress to a weak ac electric field as a probe is measured
      in a nematic liquid crystal under shear flow and dc electric fields. Two states
      with different responses are clearly observed when the dc electric field is
      changed at a constant shear rate: the flow aligning and non-flow aligning states.
      The director lies in the shear plane in the flow aligning state and out of the
      plane in the non-flow aligning state. Through application of dc electric field,
      the non-flow aligning state can be changed to the flow aligning state. In the
      transition from the flow aligning state to the non-flow aligning state, it is
      found that the response increases and the relaxation time becomes longer. Here,
      the experimental results in the flow aligning state are discussed on the basis of
      the Ericksen-Leslie theory. 

PMID- 25974518
TI  - Density of photonic states in cholesteric liquid crystals.
AB  - Density of photonic states rho(omega), group v(g), and phase v(ph) velocity of
      light, and the dispersion relation between wave vector k, and frequency omega(k)
      were determined in a cholesteric photonic crystal. A highly sensitive method
      (measurement of rotation of the plane of polarization of light) was used to
      determine rho(omega) in samples of different quality. In high-quality samples a
      drastic increase in rho(omega) near the boundaries of the stop band and
      oscillations related to Pendellosung beatings are observed. In low-quality
      samples photonic properties are strongly modified. The maximal value of
      rho(omega) is substantially smaller, and density of photonic states increases
      near the selective reflection band without oscillations in rho(omega).
      Peculiarities of rho(omega), v(g), and omega(k) are discussed. Comparison of the
      experimental results with theory was performed.

PMID- 25974519
TI  - Active one-particle microrheology of an unentangled polymer melt studied by
      molecular dynamics simulation.
AB  - We present molecular dynamics simulations for active one-particle microrheology
      of an unentangled polymer melt. The tracer particle is forced to oscillate by an
      oscillating harmonic potential, which models an experiment using optical
      tweezers. The amplitude and phase shift of this oscillation are related to the
      complex shear modulus of the polymer melt. In the linear response regime at low
      frequencies, the active microrheology gives the same result as the passive
      microrheology, where the thermal motion of a tracer particle is related to the
      complex modulus. We expand the analysis to include full hydrodynamic effects
      instead of stationary Stokes friction only, and show that different approaches
      suggested in the literature lead to completely different results, and that none
      of them improves on the description using the stationary Stokes friction. 

PMID- 25974520
TI  - Dynamics of generalized Gaussian polymeric structures in random layered flows.
AB  - We develop a formalism for the dynamics of a flexible branched polymer with
      arbitrary topology in the presence of random flows. This is achieved by employing
      the generalized Gaussian structure (GGS) approach and the Matheron-de Marsily
      model for the random layered flow. The expression for the average square
      displacement (ASD) of the center of mass of the GGS is obtained in such flow. The
      averaging is done over both the thermal noise and the external random flow.
      Although the formalism is valid for branched polymers with various complex
      topologies, we mainly focus here on the dynamics of the flexible star and
      dendrimer. We analyze the effect of the topology (the number and length of
      branches for stars and the number of generations for dendrimers) on the dynamics
      under the influence of external flow, which is characterized by their root-mean
      square velocity, persistence flow length, and flow exponent alpha. Our analysis
      shows two anomalous power-law regimes, viz., subdiffusive (intermediate-time
      polymer stretching and flow-induced diffusion) and superdiffusive (long-time flow
      induced diffusion). The influence of the topology of the GGS is unraveled in the
      intermediate-time regime, while the long-time regime is only weakly dependent on
      the topology of the polymer. With the decrease in the value of alpha, the
      magnitude of the ASD decreases, while the temporal exponent of the ASD increases
      in both the time regimes. Also there is an increase in both the magnitude of the
      ASD and the crossover time (from the subdiffusive to the superdiffusive regime)
      with an increase in the total mass of the polymeric structure. 

PMID- 25974521
TI  - Survival probability for a diffusive process on a growing domain.
AB  - We consider the motion of a diffusive population on a growing domain, 0<x<L(t),
      which is motivated by various applications in developmental biology. Individuals
      in the diffusing population, which could represent molecules or cells in a
      developmental scenario, undergo two different kinds of motion: (i) undirected
      movement, characterized by a diffusion coefficient, D, and (ii) directed
      movement, associated with the underlying domain growth. For a general class of
      problems with a reflecting boundary at x=0, and an absorbing boundary at x=L(t),
      we provide an exact solution to the partial differential equation describing the
      evolution of the population density function, C(x,t). Using this solution, we
      derive an exact expression for the survival probability, S(t), and an accurate
      approximation for the long-time limit, S=lim(t->infinity)S(t). Unlike traditional
      analyses on a nongrowing domain, where S=0, we show that domain growth leads to a
      very different situation where S can be positive. The theoretical tools developed
      and validated in this study allow us to distinguish between situations where the
      diffusive population reaches the moving boundary at x=L(t) from other situations
      where the diffusive population never reaches the moving boundary at x=L(t).
      Making this distinction is relevant to certain applications in developmental
      biology, such as the development of the enteric nervous system (ENS). All
      theoretical predictions are verified by implementing a discrete stochastic model.

PMID- 25974522
TI  - Role of protein fluctuation correlations in electron transfer in photosynthetic
      complexes.
AB  - We consider the dependence of the electron transfer in photosynthetic complexes
      on correlation properties of random fluctuations of the protein environment. The
      electron subsystem is modeled by a finite network of connected electron (exciton)
      sites. The fluctuations of the protein environment are modeled by random
      telegraph processes, which act either collectively (correlated) or independently
      (uncorrelated) on the electron sites. We derived an exact closed system of first
      order linear differential equations with constant coefficients, for the average
      density matrix elements and for their first moments. Under some conditions, we
      obtained analytic expressions for the electron transfer rates and found the range
      of parameters for their applicability by comparing with the exact numerical
      simulations. We also compared the correlated and uncorrelated regimes and
      demonstrated numerically that the uncorrelated fluctuations of the protein
      environment can, under some conditions, either increase or decrease the electron
      transfer rates. 

PMID- 25974524
TI  - Evolution of sparsity and modularity in a model of protein allostery.
AB  - The sequence of a protein is not only constrained by its physical and biochemical
      properties under current selection, but also by features of its past evolutionary
      history. Understanding the extent and the form that these evolutionary
      constraints may take is important to interpret the information in protein
      sequences. To study this problem, we introduce a simple but physical model of
      protein evolution where selection targets allostery, the functional coupling of
      distal sites on protein surfaces. This model shows how the geometrical
      organization of couplings between amino acids within a protein structure can
      depend crucially on its evolutionary history. In particular, two scenarios are
      found to generate a spatial concentration of functional constraints: high
      mutation rates and fluctuating selective pressures. This second scenario offers a
      plausible explanation for the high tolerance of natural proteins to mutations and
      for the spatial organization of their least tolerant amino acids, as revealed by
      sequence analysis and mutagenesis experiments. It also implies a faculty to adapt
      to new selective pressures that is consistent with observations. The model
      illustrates how several independent functional modules may emerge within the same
      protein structure, depending on the nature of past environmental fluctuations.
      Our model thus relates the evolutionary history of proteins to the geometry of
      their functional constraints, with implications for decoding and engineering
      protein sequences. 

PMID- 25974525
TI  - Generalized model of island biodiversity.
AB  - The dynamics of a local community of competing species with weak immigration from
      a static regional pool is studied. Implementing the generalized competitive Lotka
      Volterra model with demographic noise, a rich dynamics with four qualitatively
      distinct phases is unfolded. When the overall interspecies competition is weak,
      the island species recapitulate the mainland species. For higher values of the
      competition parameter, the system still admits an equilibrium community, but now
      some of the mainland species are absent on the island. Further increase in
      competition leads to an intermittent "disordered" phase, where the dynamics is
      controlled by invadable combinations of species and the turnover rate is governed
      by the migration. Finally, the strong competition phase is glasslike, dominated
      by uninvadable states and noise-induced transitions. Our model contains, as a
      special case, the celebrated neutral island theories of Wilson-MacArthur and
      Hubbell. Moreover, we show that slight deviations from perfect neutrality may
      lead to each of the phases, as the Hubbell point appears to be quadracritical. 

PMID- 25974523
TI  - Super-resolution two-photon microscopy via scanning patterned illumination.
AB  - We developed two-photon scanning patterned illumination microscopy (2P-SPIM) for
      super-resolution two-photon imaging. Our approach used a traditional two-photon
      microscopy setup with temporally modulated excitation to create patterned
      illumination fields. Combing nine different illuminations and structured
      illumination reconstruction, super-resolution imaging was achieved in two-photon
      microscopy. Using 2P-SPIM we achieved a lateral resolution of 141 nm, which
      represents an improvement by a factor of 1.9 over the corresponding diffraction
      limit. We further demonstrated super-resolution cellular imaging by 2P-SPIM to
      image actin cytoskeleton in mammalian cells and three-dimensional imaging in
      highly scattering retinal tissue. 

PMID- 25974526
TI  - Roots at the percolation threshold.
AB  - The rhizosphere is the layer of soil around the roots where complex and dynamic
      interactions between plants and soil affect the capacity of plants to take up
      water. The physical properties of the rhizosphere are affected by mucilage, a gel
      exuded by roots. Mucilage can absorb large volumes of water, but it becomes
      hydrophobic after drying. We use a percolation model to describe the rewetting of
      dry rhizosphere. We find that at a critical mucilage concentration the
      rhizosphere becomes impermeable. The critical mucilage concentration depends on
      the radius of the soil particle size. Capillary rise experiments with neutron
      radiography prove that for concentrations below the critical mucilage
      concentration water could easily cross the rhizosphere, while above the critical
      concentration water could no longer percolate through it. Our studies, together
      with former observations of water dynamics in the rhizosphere, suggest that the
      rhizosphere is near the percolation threshold, where small variations in mucilage
      concentration sensitively alter the soil hydraulic conductivity. Is mucilage
      exudation a plant mechanism to efficiently control the rhizosphere conductivity
      and the access to water? 

PMID- 25974527
TI  - Phase transition in random adaptive walks on correlated fitness landscapes.
AB  - We study biological evolution on a random fitness landscape where correlations
      are introduced through a linear fitness gradient of strength c. When selection is
      strong and mutations rare the dynamics is a directed uphill walk that terminates
      at a local fitness maximum. We analytically calculate the dependence of the walk
      length on the genome size L. When the distribution of the random fitness
      component has an exponential tail, we find a phase transition of the walk length
      D between a phase at small c, where walks are short (D~lnL), and a phase at large
      c, where walks are long (D~L). For all other distributions only a single phase
      exists for any c>0. The considered process is equivalent to a zero temperature
      Metropolis dynamics for the random energy model in an external magnetic field,
      thus also providing insight into the aging dynamics of spin glasses. 

PMID- 25974528
TI  - Thermodynamics predicts density-dependent energy use in organisms and ecological
      communities.
AB  - Linking our knowledge of organisms to our knowledge of ecological communities and
      ecosystems is a key challenge for ecology. Individual size distributions (ISDs)
      link the size of individual organisms to the structure of ecological communities,
      so that studying ISDs might provide insight into how organism functioning affects
      ecosystems. Similarly shaped ISDs among ecosystems, coupled with allometric links
      between organism size and resource use, suggest the possibility of emergent
      resource-use patterns in ecological communities. We drew on thermodynamics to
      develop a maximization principle that predicted both organism and community
      energy use. These predictions highlighted the importance of density-dependent
      metabolic rates and were able to explain nonlinear relationships between
      community energy use and community biomass. We analyzed data on fish community
      energy use and biomass and found evidence of nonlinear scaling, which was
      predicted by the thermodynamic principle developed here and is not explained by
      other theories of ISDs. Detailed measurements of organism energy use will clarify
      the role of density dependence in driving metabolic rates and will further test
      our derived thermodynamic principle. Importantly, our study highlights the
      potential for fundamental links between ecology and thermodynamics. 

PMID- 25974529
TI  - Pairwise amino acid secondary structural propensities.
AB  - We investigate the propensities for amino acids to form a specific secondary
      structure when they are paired with other amino acids. Our investigations use
      molecular dynamics (MD) computer simulations, and we compare the results to those
      from the Protein Data Bank (PDB). Proper comparison requires weighting of the MD
      results in a manner consistent with the relative frequency of appearance in the
      PDB of each possible pair of amino acids. We find that the propensity for an
      amino acid to assume a secondary structure varies dramatically depending on the
      amino acid that is before or after it in the primary sequence. This cooperative
      effect means that when selecting amino acids to facilitate the formation of a
      secondary structure in peptide engineering experiments, the adjacent amino acids
      must be considered. 

PMID- 25974530
TI  - Alignment and nonlinear elasticity in biopolymer gels.
AB  - We present a Landau-type theory for the nonlinear elasticity of biopolymer gels
      with a part of the order parameter describing induced nematic order of fibers in
      the gel. We attribute the nonlinear elastic behavior of these materials to fiber
      alignment induced by strain. We suggest an application to contact guidance of
      cell motility in tissue. We compare our theory to simulation of a disordered
      lattice model for biopolymers. We treat homogeneous deformations such as simple
      shear, hydrostatic expansion, and simple extension, and obtain good agreement
      between theory and simulation. We also consider a localized perturbation which is
      a simple model for a contracting cell in a medium. 

PMID- 25974531
TI  - Mathematical modeling of bacterial track-altering motors: Track cleaving through
      burnt-bridge ratchets.
AB  - The generation of directed movement of cellular components frequently requires
      the rectification of Brownian motion. Molecular motor enzymes that use ATP to
      walk on filamentous tracks are typically involved in cell transport, however, a
      track-altering motor can arise when an enzyme interacts with and alters its
      track. In Caulobacter crescentus and other bacteria, an active DNA partitioning
      (Par) apparatus is employed to segregate replicated chromosome regions to
      specific locations in dividing cells. The Par apparatus is composed of two
      proteins: ParA, an ATPase that can form polymeric structures on the nucleoid, and
      ParB, a protein that can bind and destabilize ParA structures. It has been
      proposed that the ParB-mediated alteration of ParA structures could be
      responsible for generating the directed movement of DNA during bacterial
      division. How precisely these actions are coordinated and translated into
      directed movement is not clear. In this paper we consider the C. crescentus
      segregation apparatus as an example of a track altering motor that operates using
      a so-called burnt-bridge mechanism. We develop and analyze mathematical models
      that examine how diffusion and ATP-hydrolysis-mediated monomer removal (or
      cleaving) can be combined to generate directed movement. Using a mean first
      passage approach, we analytically calculate the effective ParA track-cleaving
      velocities, effective diffusion coefficient, and other higher moments for the
      movement a ParB protein cluster that breaks monomers away at random locations on
      a single ParA track. Our model results indicate that cleaving velocities and
      effective diffusion constants are sensitive to ParB-induced ATP hydrolysis rates.
      Our analytical results are in excellent agreement with stochastic simulation
      results. 

PMID- 25974532
TI  - Quiet swimming at low Reynolds number.
AB  - The stresslet provides a simple model of the flow created by a small, freely
      swimming and neutrally buoyant aquatic organism and shows that the far field
      fluid disturbance created by such an organism in general decays as one over
      distance squared. Here we discuss a quieter swimming mode that eliminates the
      stresslet component of the flow and leads to a faster spatial decay of the fluid
      disturbance described by a force quadrupole that decays as one over distance
      cubed. Motivated by recent experimental results on fluid disturbances due to
      small aquatic organisms, we demonstrate that a three-Stokeslet model of a
      swimming organism which uses breast stroke type kinematics is an example of such
      a quiet swimmer. We show that the fluid disturbance in both the near field and
      the far field is significantly reduced by appropriately arranging the propulsion
      apparatus, and we find that the far field power laws are valid surprisingly close
      to the organism. Finally, we discuss point force models as a general framework
      for hypothesis generation and experimental exploration of fluid mediated predator
      prey interactions in the planktonic world. 

PMID- 25974533
TI  - Stepping molecular motor amid Levy white noise.
AB  - We consider a model of a stepping molecular motor consisting of two connected
      heads. Directional motion of the stepper takes place along a one-dimensional
      track. Each head is subject to a periodic potential without spatial reflection
      symmetry. When the potential for one head is switched on, it is switched off for
      the other head. Additionally, the system is subject to the influence of
      symmetric, white Levy noise that mimics the action of external random forcing.
      The stepper exhibits motion with a preferred direction which is examined by
      analyzing the median of the displacement of a midpoint between the positions of
      the two heads. We study the modified dynamics of the stepper by numerical
      simulations. We find flux reversals as noise parameters are changed. Speed and
      direction appear to very sensitively depend on characteristics of the noise. 

PMID- 25974534
TI  - Optimal search in E. coli chemotaxis.
AB  - We study chemotaxis of a single E. coli bacterium in a medium where the nutrient
      chemical is also undergoing diffusion and its concentration has the form of a
      Gaussian whose width increases with time. We measure the average first passage
      time of the bacterium at a region of high nutrient concentration. In the limit of
      very slow nutrient diffusion, the bacterium effectively experiences a Gaussian
      concentration profile with a fixed width. In this case we find that there exists
      an optimum width of the Gaussian when the average first passage time is minimum,
      i.e., the search process is most efficient. We verify the existence of the
      optimum width for the deterministic initial position of the bacterium and also
      for the stochastic initial position, drawn from uniform and steady state
      distributions. Our numerical simulation in a model of a non-Markovian random
      walker agrees well with our analytical calculations in a related coarse-grained
      model. We also present our simulation results for the case when the nutrient
      diffusion and bacterial motion occur over comparable time scales and the
      bacterium senses a time-varying concentration field. 

PMID- 25974535
TI  - Kinetics of virus entry by endocytosis.
AB  - Entry of virions into the host cells is either endocytotic or fusogenic. In both
      cases, it occurs via reversible formation of numerous relatively weak bonds
      resulting in wrapping of a virion by the host membrane with subsequent membrane
      rupture or scission. The corresponding kinetic models are customarily focused on
      the formation of bonds and do not pay attention to the energetics of the whole
      process, which is crucially dependent, especially in the case of endocytosis, on
      deformation of actin filaments forming the cytoskeleton of the host cell. The
      kinetic model of endocytosis, proposed by the author, takes this factor into
      account and shows that the whole process can be divided into a rapid initial
      transient stage and a long steady-state stage. The entry occurs during the latter
      stage and can be described as a first-order reaction. Depending on the details of
      the dependence of the grand canonical potential on the number of bonds, the entry
      can be limited either by the interplay of bond formation and membrane rupture (or
      scission) or by reaching a maximum of this potential. 

PMID- 25974536
TI  - Fractional dynamics in silk: From molecular picosecond subdiffusion to
      macroscopic long-time relaxation.
AB  - Structural relaxations in humid silk fibers exposed to tensile stress have been
      reported to take place on a very wide range of time scales from a few
      milliseconds to several hours. The time-dependence of the measured tensile force
      following a quasi-instantaneously applied external strain on the fibers can be
      understood in terms of a fractional viscoelastic relaxation function introducing
      memory effects by which the mechanical state of a fiber depends on its tensile
      history. An analog fractional relaxation also gives rise to the subdiffusion
      observed on picosecond time scales, which governs the mobility of the amorphous
      polymer chains and adsorbed water on the molecular level. The reduction of the
      subdiffusive memory effect in stretched fibers compared to native fibers is
      consistent with the higher order of the polymers in the stretched state. 

PMID- 25974537
TI  - Coding stimulus amplitude by correlated neural activity.
AB  - While correlated activity is observed ubiquitously in the brain, its role in
      neural coding has remained controversial. Recent experimental results have
      demonstrated that correlated but not single-neuron activity can encode the
      detailed time course of the instantaneous amplitude (i.e., envelope) of a
      stimulus. These have furthermore demonstrated that such coding required and was
      optimal for a nonzero level of neural variability. However, a theoretical
      understanding of these results is still lacking. Here we provide a comprehensive
      theoretical framework explaining these experimental findings. Specifically, we
      use linear response theory to derive an expression relating the correlation
      coefficient to the instantaneous stimulus amplitude, which takes into account key
      single-neuron properties such as firing rate and variability as quantified by the
      coefficient of variation. The theoretical prediction was in excellent agreement
      with numerical simulations of various integrate-and-fire type neuron models for
      various parameter values. Further, we demonstrate a form of stochastic resonance
      as optimal coding of stimulus variance by correlated activity occurs for a
      nonzero value of noise intensity. Thus, our results provide a theoretical
      explanation of the phenomenon by which correlated but not single-neuron activity
      can code for stimulus amplitude and how key single-neuron properties such as
      firing rate and variability influence such coding. Correlation coding by
      correlated but not single-neuron activity is thus predicted to be a ubiquitous
      feature of sensory processing for neurons responding to weak input. 

PMID- 25974538
TI  - Breaking DNA strands by extreme-ultraviolet laser pulses in vacuum.
AB  - Ionizing radiation induces a variety of DNA damages including single-strand
      breaks (SSBs), double-strand breaks (DSBs), abasic sites, modified sugars, and
      bases. Most theoretical and experimental studies have been focused on DNA strand
      scissions, in particular production of DNA double-strand breaks. DSBs have been
      proven to be a key damage at a molecular level responsible for the formation of
      chromosomal aberrations, leading often to cell death. We have studied the nature
      of DNA damage induced directly by the pulsed 46.9-nm (26.5 eV) radiation provided
      by an extreme ultraviolet (XUV) capillary-discharge Ne-like Ar laser (CDL). Doses
      up to 45 kGy were delivered with a repetition rate of 3 Hz. We studied the
      dependence of the yield of SSBs and DSBs of a simple model of DNA molecule
      (pBR322) on the CDL pulse fluence. Agarose gel electrophoresis method was used
      for determination of both SSB and DSB yields. The action cross sections of the
      single- and double-strand breaks of pBR322 plasmid DNA in solid state were
      determined. We observed an increase in the efficiency of strand-break induction
      in the supercoiled DNA as a function of laser pulse fluence. Results are compared
      to those acquired at synchrotron radiation facilities and other sources of
      extreme-ultraviolet and soft x-ray radiation. 

PMID- 25974539
TI  - Approximate analytical solutions for excitation and propagation in cardiac
      tissue.
AB  - It is well known that a variety of cardiac arrhythmias are initiated by a focal
      excitation in heart tissue. At the single cell level these currents are typically
      induced by intracellular processes such as spontaneous calcium release (SCR).
      However, it is not understood how the size and morphology of these focal
      excitations are related to the electrophysiological properties of cardiac cells.
      In this paper a detailed physiologically based ionic model is analyzed by
      projecting the excitation dynamics to a reduced one-dimensional parameter space.
      Based on this analysis we show that the inward current required for an excitation
      to occur is largely dictated by the voltage dependence of the inward rectifier
      potassium current (I(K1)), and is insensitive to the detailed properties of the
      sodium current. We derive an analytical expression relating the size of a
      stimulus and the critical current required to induce a propagating action
      potential (AP), and argue that this relationship determines the necessary number
      of cells that must undergo SCR in order to induce ectopic activity in cardiac
      tissue. Finally, we show that, once a focal excitation begins to propagate, its
      propagation characteristics, such as the conduction velocity and the critical
      radius for propagation, are largely determined by the sodium and gap junction
      currents with a substantially lesser effect due to repolarizing potassium
      currents. These results reveal the relationship between ion channel properties
      and important tissue scale processes such as excitation and propagation.

PMID- 25974540
TI  - Optimal chemotaxis in intermittent migration of animal cells.
AB  - Animal cells can sense chemical gradients without moving and are faced with the
      challenge of migrating towards a target despite noisy information on the target
      position. Here we discuss optimal search strategies for a chaser that moves by
      switching between two phases of motion ("run" and "tumble"), reorienting itself
      towards the target during tumble phases, and performing persistent migration
      during run phases. We show that the chaser average run time can be adjusted to
      minimize the target catching time or the spatial dispersion of the chasers. We
      obtain analytical results for the catching time and for the spatial dispersion in
      the limits of small and large ratios of run time to tumble time and scaling laws
      for the optimal run times. Our findings have implications for optimal chemotactic
      strategies in animal cell migration. 

PMID- 25974541
TI  - Growing optimal scale-free networks via likelihood.
AB  - Preferential attachment, by which new nodes attach to existing nodes with
      probability proportional to the existing nodes' degree, has become the standard
      growth model for scale-free networks, where the asymptotic probability of a node
      having degree k is proportional to k^{-gamma}. However, the motivation for this
      model is entirely ad hoc. We use exact likelihood arguments and show that the
      optimal way to build a scale-free network is to attach most new links to nodes of
      low degree. Curiously, this leads to a scale-free network with a single dominant
      hub: a starlike structure we call a superstar network. Asymptotically, the
      optimal strategy is to attach each new node to one of the nodes of degree k with
      probability proportional to 1/N+zeta(gamma)(k+1)(gamma) (in a N node network): a
      stronger bias toward high degree nodes than exhibited by standard preferential
      attachment. Our algorithm generates optimally scale-free networks (the superstar
      networks) as well as randomly sampling the space of all scale-free networks with
      a given degree exponent gamma. We generate viable realization with finite N for
      1?gamma<2 as well as gamma>2. We observe an apparently discontinuous transition
      at gamma~2 between so-called superstar networks and more treelike realizations.
      Gradually increasing gamma further leads to reemergence of a superstar hub. To
      quantify these structural features, we derive a new analytic expression for the
      expected degree exponent of a pure preferential attachment process and introduce
      alternative measures of network entropy. Our approach is generic and can also be
      applied to an arbitrary degree distribution.

PMID- 25974542
TI  - Cumulants of Hawkes point processes.
AB  - We derive explicit, closed-form expressions for the cumulant densities of a
      multivariate, self-exciting Hawkes point process, generalizing a result of Hawkes
      in his earlier work on the covariance density and Bartlett spectrum of such
      processes. To do this, we represent the Hawkes process in terms of a Poisson
      cluster process and show how the cumulant density formulas can be derived by
      enumerating all possible "family trees," representing complex interactions
      between point events. We also consider the problem of computing the integrated
      cumulants, characterizing the average measure of correlated activity between
      events of different types, and derive the relevant equations. 

PMID- 25974543
TI  - Using trading strategies to detect phase transitions in financial markets.
AB  - We show that the log-periodic power law singularity model (LPPLS), a mathematical
      embodiment of positive feedbacks between agents and of their hierarchical
      dynamical organization, has a significant predictive power in financial markets.
      We find that LPPLS-based strategies significantly outperform the randomized ones
      and that they are robust with respect to a large selection of assets and time
      periods. The dynamics of prices thus markedly deviate from randomness in certain
      pockets of predictability that can be associated with bubble market regimes. Our
      hybrid approach, marrying finance with the trading strategies, and critical
      phenomena with LPPLS, demonstrates that targeting information related to phase
      transitions enables the forecast of financial bubbles and crashes punctuating the
      dynamics of prices. 

PMID- 25974544
TI  - Impact of self-healing capability on network robustness.
AB  - A wide spectrum of real-life systems ranging from neurons to botnets display
      spontaneous recovery ability. Using the generating function formalism applied to
      static uncorrelated random networks with arbitrary degree distributions, the
      microscopic mechanism underlying the depreciation-recovery process is
      characterized and the effect of varying self-healing capability on network
      robustness is revealed. It is found that the self-healing capability of nodes has
      a profound impact on the phase transition in the emergence of percolating
      clusters, and that salient difference exists in upholding network integrity under
      random failures and intentional attacks. The results provide a theoretical
      framework for quantitatively understanding the self-healing phenomenon in varied
      complex systems. 

PMID- 25974545
TI  - Random rectangular graphs.
AB  - A generalization of the random geometric graph (RGG) model is proposed by
      considering a set of points uniformly and independently distributed on a
      rectangle of unit area instead of on a unit square [0,1](2). The topological
      properties of the random rectangular graphs (RRGs) generated by this model are
      then studied as a function of the rectangle sides lengths a and b=1/a, and the
      radius r used to connect the nodes. When a=1 we recover the RGG, and when a
      >infinity the very elongated rectangle generated resembles a one-dimensional RGG.
      We obtain here analytical expressions for the average degree, degree
      distribution, connectivity, average path length, and clustering coefficient for
      RRG. These results provide evidence that show that most of these properties
      depend on the connection radius and the side length of the rectangle, usually in
      a monotonic way. The clustering coefficient, however, increases when the square
      is transformed into a slightly elongated rectangle, and after this maximum it
      decays with the increase of the elongation of the rectangle. We support all our
      findings by computational simulations that show the goodness of the theoretical
      models proposed for RRGs.

PMID- 25974546
TI  - Kinetic models for historical processes of fast invasion and aggression.
AB  - In the last few decades many investigations have been devoted to theoretical
      models in new areas concerning description of different biological, sociological,
      and historical processes. In the present paper we suggest a model of the Nazi
      Germany invasion of Poland, France, and the USSR based on kinetic theory. We
      simulate this process with the Cauchy boundary problem for two-element kinetic
      equations. The solution of the problem is given in the form of a traveling wave.
      The propagation velocity of a front line depends on the quotient between initial
      forces concentrations. Moreover it is obtained that the general solution of the
      model can be expressed in terms of quadratures and elementary functions. Finally
      it is shown that the front-line velocities agree with the historical data. 

PMID- 25974547
TI  - Analytical description for the critical fixations of evolutionary coordination
      games on finite complex structured populations.
AB  - Evolutionary game theory is crucial to capturing the characteristic interaction
      patterns among selfish individuals. In a population of coordination games of two
      strategies, one of the central problems is to determine the fixation probability
      that the system reaches a state of networkwide of only one strategy, and the
      corresponding expectation times. The deterministic replicator equations predict
      the critical value of initial density of one strategy, which separates the two
      absorbing states of the system. However, numerical estimations of this separatrix
      show large deviations from the theory in finite populations. Here we provide a
      stochastic treatment of this dynamic process on complex networks of finite sizes
      as Markov processes, showing the evolutionary time explicitly. We describe
      analytically the effects of network structures on the intermediate fixations as
      observed in numerical simulations. Our theoretical predictions are validated by
      various simulations on both random and scale free networks. Therefore, our
      stochastic framework can be helpful in dealing with other networked game
      dynamics. 

PMID- 25974548
TI  - Eigenspectrum bounds for semirandom matrices with modular and spatial structure
      for neural networks.
AB  - The eigenvalue spectrum of the matrix of directed weights defining a neural
      network model is informative of several stability and dynamical properties of
      network activity. Existing results for eigenspectra of sparse asymmetric random
      matrices neglect spatial or other constraints in determining entries in these
      matrices, and so are of partial applicability to cortical-like architectures.
      Here we examine a parameterized class of networks that are defined by sparse
      connectivity, with connection weighting modulated by physical proximity (i.e.,
      asymmetric Euclidean random matrices), modular network partitioning, and
      functional specificity within the excitatory population. We present a set of
      analytical constraints that apply to the eigenvalue spectra of associated weight
      matrices, highlighting the relationship between connectivity rules and classes of
      network dynamics. 

PMID- 25974549
TI  - Crafting networks to achieve, or not achieve, chaotic states.
AB  - The influence of networks topology on collective properties of dynamical systems
      defined upon it is studied in the thermodynamic limit. A network model
      construction scheme is proposed where the number of links and the average
      eccentricity are controlled. This is done by rewiring links of a regular one
      dimensional chain according to a probability p within a specific range r that can
      depend on the number of vertices N. We compute the thermodynamical behavior of a
      system defined on the network, the XY-rotors model, and monitor how it is
      affected by the topological changes. We identify the network effective dimension
      d as a crucial parameter: topologies with d<2 exhibit no phase transitions, while
      topologies with d>2 display a second-order phase transition. Topologies with d=2
      exhibit states characterized by infinite susceptibility and macroscopic chaotic,
      turbulent dynamical behavior. These features are also captured by d in the finite
      size context. 

PMID- 25974550
TI  - Social exclusion in finite populations.
AB  - Social exclusion, keeping free riders from benefit sharing, plays an important
      role in sustaining cooperation in our world. Here we propose two different
      exclusion regimes, namely, peer exclusion and pool exclusion, to investigate the
      evolution of social exclusion in finite populations. In the peer exclusion
      regime, each excluder expels all the defectors independently, and thus bears the
      total cost on his own, while in the pool exclusion regime, excluders
      spontaneously form an institution to carry out rejection of the free riders, and
      each excluder shares the cost equally. In a public goods game containing only
      excluders and defectors, it is found that peer excluders outperform pool
      excluders if the exclusion costs are small, and the situation is converse once
      the exclusion costs exceed some critical points, which holds true for all the
      selection intensities and different update rules. Moreover, excluders can
      dominate the whole population under a suitable parameters range in the presence
      of second-order free riders (cooperators), showing that exclusion has prominent
      advantages over common costly punishment. More importantly, our finding indicates
      that the group exclusion mechanism helps the cooperative union to survive under
      unfavorable conditions. Our results may give some insights into better
      understanding the prevalence of such a strategy in the real world and its
      significance in sustaining cooperation. 

PMID- 25974551
TI  - Time evolution of predictability of epidemics on networks.
AB  - Epidemic outbreaks of new pathogens, or known pathogens in new populations, cause
      a great deal of fear because they are hard to predict. For theoretical models of
      disease spreading, on the other hand, quantities characterizing the outbreak
      converge to deterministic functions of time. Our goal in this paper is to shed
      some light on this apparent discrepancy. We measure the diversity of (and, thus,
      the predictability of) outbreak sizes and extinction times as functions of time
      given different scenarios of the amount of information available. Under the
      assumption of perfect information-i.e., knowing the state of each individual with
      respect to the disease-the predictability decreases exponentially, or faster,
      with time. The decay is slowest for intermediate values of the per-contact
      transmission probability. With a weaker assumption on the information available,
      assuming that we know only the fraction of currently infectious, recovered, or
      susceptible individuals, the predictability also decreases exponentially most of
      the time. There are, however, some peculiar regions in this scenario where the
      predictability decreases. In other words, to predict its final size with a given
      accuracy, we would need increasingly more information about the outbreak. 

PMID- 25974552
TI  - Proof of uniform sampling of binary matrices with fixed row sums and column sums
      for the fast Curveball algorithm.
AB  - Randomization of binary matrices has become one of the most important
      quantitative tools in modern computational biology. The equivalent problem of
      generating random directed networks with fixed degree sequences has also
      attracted a lot of attention. However, it is very challenging to generate truly
      unbiased random matrices with fixed row and column sums. Strona et al. [Nat.
      Commun. 5, 4114 (2014)] introduce the innovative Curveball algorithm and give
      numerical support for the proposition that it generates truly random matrices. In
      this paper, we present a rigorous proof of convergence to the uniform
      distribution. Furthermore, we show the Curveball algorithm must include certain
      failed trades to ensure uniform sampling.

PMID- 25974553
TI  - Robustness of spatial micronetworks.
AB  - Power lines, roadways, pipelines, and other physical infrastructure are critical
      to modern society. These structures may be viewed as spatial networks where
      geographic distances play a role in the functionality and construction cost of
      links. Traditionally, studies of network robustness have primarily considered the
      connectedness of large, random networks. Yet for spatial infrastructure, physical
      distances must also play a role in network robustness. Understanding the
      robustness of small spatial networks is particularly important with the
      increasing interest in microgrids, i.e., small-area distributed power grids that
      are well suited to using renewable energy resources. We study the random failures
      of links in small networks where functionality depends on both spatial distance
      and topological connectedness. By introducing a percolation model where the
      failure of each link is proportional to its spatial length, we find that when
      failures depend on spatial distances, networks are more fragile than expected.
      Accounting for spatial effects in both construction and robustness is important
      for designing efficient microgrids and other network infrastructure. 

PMID- 25974555
TI  - Extraction of conjugate main-stream structures from a complex network flow.
AB  - We introduce a method to extract main-stream structures for a given complex
      network flow by trimming less effective links. As the resulting main streams
      generally have an almost loopless treelike structure, we can define the stream
      basin size for each node, which characterizes the importance of the node with
      regard to the flow. As a real-world example, we apply this method to an interfirm
      trading network, both for the money flow and its conjugate-the material or
      service flow-confirming that both basin size distributions follow a similar power
      law that differs significantly from the basin size distributions of rivers in
      nature. We theoretically analyze the process of trimming and derive a consistent
      statistical formulation between the original link number and the basin size. 

PMID- 25974554
TI  - Analyzing network reliability using structural motifs.
AB  - This paper uses the reliability polynomial, introduced by Moore and Shannon in
      1956, to analyze the effect of network structure on diffusive dynamics such as
      the spread of infectious disease. We exhibit a representation for the reliability
      polynomial in terms of what we call structural motifs that is well suited for
      reasoning about the effect of a network's structural properties on diffusion
      across the network. We illustrate by deriving several general results relating
      graph structure to dynamical phenomena. 

PMID- 25974556
TI  - Chaos and band structure in a three-dimensional optical lattice.
AB  - Classical chaos is known to affect wave propagation because it signifies the
      presence of broken symmetries. The effect of chaos has been observed
      experimentally for matter waves, electromagnetic waves, and acoustic waves. When
      these three types of waves propagate through a spatially periodic medium, the
      allowed propagation energies form bands. For energies in the band gaps, no wave
      propagation is possible. We show that optical lattices provide a well-defined
      system that allows a study of the effect of chaos on band structure. We have
      determined the band structure of a body-centered-cubic optical lattice for all
      theoretically possible couplings, and we find that the band structure for those
      lattices realizable in the laboratory differs significantly from that expected
      for the bands in an "empty" body-centered-cubic crystal. However, as coupling is
      increased, the lattice becomes increasingly chaotic and it becomes possible to
      produce band structure that has behavior qualitatively similar to the "empty"
      body-centered-cubic band structure, although with fewer degeneracies. 

PMID- 25974557
TI  - Dynamics of kink, antikink, bright, generalized Jacobi elliptic function
      solutions of matter-wave condensates with time-dependent two- and three-body
      interactions.
AB  - By using the F-expansion method associated with four auxiliary equations, i.e.,
      the Bernoulli equation, the Riccati equation, the Lenard equation, and the
      hyperbolic equation, we present exact explicit solutions describing the dynamics
      of matter-wave condensates with time-varying two- and three-body nonlinearities.
      Condensates are trapped in a harmonic potential and they exchange atoms with the
      thermal cloud. These solutions include the generalized Jacobi elliptic function
      solutions, hyperbolic function solutions, and trigonometric function solutions.
      In addition, we have also found rational function solutions. Solutions
      constructed here have many free parameters that can be used to manipulate and
      control some important features of the condensate, such as the position, width,
      velocity, acceleration, and homogeneous phase. The stability of the solutions is
      confirmed by their long-time numerical behavior. 

PMID- 25974558
TI  - Fermi resonance in optical microcavities.
AB  - Fermi resonance is a phenomenon of quantum mechanical superposition, which most
      often occurs between normal and overtone modes in molecular systems that are
      nearly coincident in energy. We find that scarred resonances in deformed
      dielectric microcavities are the very phenomenon of Fermi resonance, that is, a
      pair of quasinormal modes interact with each other due to coupling and a pair of
      resonances are generated through an avoided resonance crossing. Then the quantum
      number difference of a pair of quasinormal modes, which is a consequence of
      quantum mechanical superposition, equals periodic orbits, whereby the resonances
      are localized on the periodic orbits. We derive the relation between the quantum
      number difference and the periodic orbits and confirm it in an elliptic, a
      rectangular, and a stadium-shaped dielectric microcavity. 

PMID- 25974559
TI  - Statistical properties of the localization measure in a finite-dimensional model
      of the quantum kicked rotator.
AB  - We study the quantum kicked rotator in the classically fully chaotic regime K=10
      and for various values of the quantum parameter k using Izrailev's N-dimensional
      model for various N<=3000, which in the limit N->infinity tends to the exact
      quantized kicked rotator. By numerically calculating the eigenfunctions in the
      basis of the angular momentum we find that the localization length L for fixed
      parameter values has a certain distribution; in fact, its inverse is Gaussian
      distributed, in analogy and in connection with the distribution of finite time
      Lyapunov exponents of Hamilton systems. However, unlike the case of the finite
      time Lyapunov exponents, this distribution is found to be independent of N and
      thus survives the limit N=infinity. This is different from the tight-binding
      model of Anderson localization. The reason is that the finite bandwidth
      approximation of the underlying Hamilton dynamical system in the Shepelyansky
      picture [Phys. Rev. Lett. 56, 677 (1986)] does not apply rigorously. This
      observation explains the strong fluctuations in the scaling laws of the kicked
      rotator, such as the entropy localization measure as a function of the scaling
      parameter Lambda=L/N, where L is the theoretical value of the localization length
      in the semiclassical approximation. These results call for a more refined theory
      of the localization length in the quantum kicked rotator and in similar Floquet
      systems, where we must predict not only the mean value of the inverse of the
      localization length L but also its (Gaussian) distribution, in particular the
      variance. In order to complete our studies we numerically analyze the related
      behavior of finite time Lyapunov exponents in the standard map and of the 2*2
      transfer matrix formalism. This paper extends our recent work [Phys. Rev. E 87,
      062905 (2013)].

PMID- 25974560
TI  - Interaction of Lyapunov vectors in the formulation of the nonlinear extension of
      the Kalman filter.
AB  - When applied to strongly nonlinear chaotic dynamics the extended Kalman filter
      (EKF) is prone to divergence due to the difficulty of correctly forecasting the
      forecast error probability density function. In operational forecasting
      applications ensemble Kalman filters circumvent this problem with empirical
      procedures such as covariance inflation. This paper presents an extension of the
      EKF that includes nonlinear terms in the evolution of the forecast error
      estimate. This is achieved starting from a particular square-root implementation
      of the EKF with assimilation confined in the unstable subspace (EKF-AUS), that
      is, the span of the Lyapunov vectors with non-negative exponents. When the error
      evolution is nonlinear, the space where it is confined is no more restricted to
      the unstable and neutral subspace causing filter divergence. The algorithm
      presented here, denominated EKF-AUS-NL, includes the nonlinear terms in the error
      dynamics: These result from the nonlinear interaction among the leading Lyapunov
      vectors and account for all directions where the error growth may take place.
      Numerical results show that with the nonlinear terms included, filter divergence
      can be avoided. We test the algorithm on the Lorenz96 model, showing very
      promising results. 

PMID- 25974561
TI  - Bipartite networks of oscillators with distributed delays: Synchronization
      branches and multistability.
AB  - We study synchronization in bipartite networks of phase oscillators with general
      nonlinear coupling and distributed time delays. Phase-locked solutions are shown
      to arise, where the oscillators in each partition are perfectly synchronized
      among themselves but can have a phase difference with the other partition, with
      the phase difference necessarily being either zero or pi radians. Analytical
      conditions for the stability of both types of solutions are obtained and solution
      branches are explicitly calculated, revealing that the network can have several
      coexisting stable solutions. With increasing value of the mean delay, the system
      exhibits hysteresis, phase flips, final state sensitivity, and an extreme form of
      multistability where the numbers of stable in-phase and antiphase synchronous
      solutions with distinct frequencies grow without bound. The theory is applied to
      networks of Landau-Stuart and Rossler oscillators and shown to accurately predict
      both in-phase and antiphase synchronous behavior in appropriate parameter ranges.

PMID- 25974562
TI  - Pattern-fluid interpretation of chemical turbulence.
AB  - The spontaneous formation of heterogeneous patterns is a hallmark of many
      nonlinear systems, from biological tissue to evolutionary population dynamics.
      The standard model for pattern formation in general, and for Turing patterns in
      chemical reaction-diffusion systems in particular, are deterministic nonlinear
      partial differential equations where an unstable homogeneous solution gives way
      to a stable heterogeneous pattern. However, these models fail to fully explain
      the experimental observation of turbulent patterns with spatio-temporal disorder
      in chemical systems. Here we introduce a pattern-fluid model as a general concept
      where turbulence is interpreted as a weakly interacting ensemble obtained by
      random superposition of stationary solutions to the underlying reaction-diffusion
      system. The transition from turbulent to stationary patterns is then interpreted
      as a condensation phenomenon, where the nonlinearity forces one single mode to
      dominate the ensemble. This model leads to better reproduction of the
      experimental concentration profiles for the "stationary phases" and reproduces
      the turbulent chemical patterns observed by Q. Ouyang and H. L. Swinney [Chaos 1,
      411 (1991)].

PMID- 25974563
TI  - Symmetries and exact solutions of a class of nonlocal nonlinear Schrodinger
      equations with self-induced parity-time-symmetric potential.
AB  - A class of nonlocal nonlinear Schrodinger equations (NLSEs) is considered in an
      external potential with a space-time modulated coefficient of the nonlinear
      interaction term as well as confining and/or loss-gain terms. This is a
      generalization of a recently introduced integrable nonlocal NLSE with self
      induced potential that is parity-time-symmetric in the corresponding stationary
      problem. Exact soliton solutions are obtained for the inhomogeneous and/or
      nonautonomous nonlocal NLSE by using similarity transformation, and the method is
      illustrated with a few examples. It is found that only those transformations are
      allowed for which the transformed spatial coordinate is odd under the parity
      transformation of the original one. It is shown that the nonlocal NLSE without
      the external potential and a (d+1)-dimensional generalization of it admits all
      the symmetries of the (d+1)-dimensional Schrodinger group. The conserved Noether
      charges associated with the time translation, dilatation, and special conformal
      transformation are shown to be real-valued in spite of being non-Hermitian.
      Finally, the dynamics of different moments are studied with an exact description
      of the time evolution of the "pseudowidth" of the wave packet for the special
      case in which the system admits a O(2,1) conformal symmetry. 

PMID- 25974564
TI  - Bright, dark, and mixed vector soliton solutions of the general coupled nonlinear
      Schrodinger equations.
AB  - The reduction procedure for the general coupled nonlinear Schrodinger (GCNLS)
      equations with four-wave mixing terms is proposed. It is shown that the GCNLS
      system is equivalent to the well known integrable families of the Manakov and
      Makhankov U(n,m)-vector models. This equivalence allows us to construct bright
      bright and dark-dark solitons and a quasibreather-dark solution with
      unconventional dynamics: the density of the first component oscillates in space
      and time, whereas the density of the second component does not. The collision
      properties of solitons are also studied. 

PMID- 25974565
TI  - Renormalized phonons in nonlinear lattices: A variational approach.
AB  - We propose a variational approach to study renormalized phonons in momentum
      conserving nonlinear lattices with either symmetric or asymmetric potentials. To
      investigate the influence of pressure for phonon properties, we derive an
      inequality which provides both the lower and upper bound of the Gibbs free energy
      as the associated variational principle. This inequality is a direct extension to
      the Gibbs-Bogoliubov inequality. Taking the symmetry effect into account, the
      reference system for the variational approach is chosen to be harmonic with an
      asymmetric quadratic potential which contains variational parameters. We
      demonstrate the power of this approach by applying it to one-dimensional
      nonlinear lattices with a symmetric or asymmetric Fermi-Pasta-Ulam-type
      potential. For a system with a symmetric potential and zero pressure, we recover
      existing results. For other systems which are beyond the scope of existing
      theories, including those having symmetric potential and pressure and those
      having the asymmetric potential with or without pressure, we also obtain accurate
      sound velocity. 

PMID- 25974566
TI  - Local quantum ergodic conjecture.
AB  - The quantum ergodic conjecture equates the Wigner function for a typical
      eigenstate of a classically chaotic Hamiltonian with a delta function on the
      energy shell. This ensures the evaluation of classical ergodic expectations of
      simple observables, in agreement with Shnirelman's theorem, but this putative
      Wigner function violates several important requirements. Consequently, we
      transfer the conjecture to the Fourier transform of the Wigner function, that is,
      the chord function. We show that all the relevant consequences of the usual
      conjecture require only information contained within a small (Planck) volume
      around the origin of the phase space of chords: translations in ordinary phase
      space. Loci of complete orthogonality between a given eigenstate and its nearby
      translation are quite elusive for the Wigner function, but our local conjecture
      stipulates that their pattern should be universal for ergodic eigenstates of the
      same Hamiltonian lying within a classically narrow energy range. Our findings are
      supported by numerical evidence in a Hamiltonian exhibiting soft chaos. Heavily
      scarred eigenstates are remarkable counter-examples of the ergodic universal
      pattern. 

PMID- 25974567
TI  - Variational superposed Gaussian approximation for time-dependent solutions of
      Langevin equations.
AB  - We propose a variational superposed Gaussian approximation (VSGA) for dynamical
      solutions of Langevin equations subject to applied signals, determining time
      dependent parameters of superposed Gaussian distributions by the variational
      principle. We apply the proposed VSGA to systems driven by a chaotic signal,
      where the conventional Fourier method cannot be adopted, and calculate the time
      evolution of probability density functions (PDFs) and moments. Both white and
      colored Gaussian noises terms are included to describe fluctuations. Our
      calculations show that time-dependent PDFs obtained by VSGA agree excellently
      with those obtained by Monte Carlo simulations. The correlation between the
      chaotic input signal and the mean response are also calculated as a function of
      the noise intensity, which confirms the occurrence of aperiodic stochastic
      resonance with both white and colored noises. 

PMID- 25974568
TI  - Origin of the enhancement of tunneling probability in the nearly integrable
      system.
AB  - The enhancement of tunneling probability in the nearly integrable system is
      closely examined, focusing on tunneling splittings plotted as a function of the
      inverse of the Planck's constant. On the basis of the analysis using the absorber
      which efficiently suppresses the coupling, creating spikes in the plot, we found
      that the splitting curve should be viewed as the staircase-shaped skeleton
      accompanied by spikes. We further introduce renormalized integrable Hamiltonians
      and explore the origin of such a staircase structure by investigating the nature
      of eigenfunctions closely. It is found that the origin of the staircase structure
      could trace back to the anomalous structure in tunneling tail which manifests
      itself in the representation using renormalized action bases. This also explains
      the reason why the staircase does not appear in the completely integrable system.

PMID- 25974569
TI  - Numerical study of extreme events in a laser diode with phase-conjugate optical
      feedback.
AB  - Extreme intensity pulses sharing statistical properties similar to rogue waves
      have been recently observed in a laser diode with phase-conjugate feedback [A.
      Karsaklian Dal Bosco, D. Wolfersberger, and M. Sciamanna, Opt. Lett. 38, 703
      (2013)], but remain unexplained. We demonstrate here that a rate equation model
      of a laser diode that includes an instantaneous phase-conjugate feedback field
      reproduces qualitatively well the statistical features of these extreme events as
      identified in the experiment, i.e., the deviation of the intensity statistics to
      a Gaussian-shape statistics and the statistics of the time separating extreme
      events. The numerical simulations confirm the importance of the feedback strength
      in increasing the number of such extreme events and allow us to explain how
      extreme events emerge from a sequence of bifurcations on self-pulsating
      solutions, the so-called external cavity modes.

PMID- 25974570
TI  - Global change in action due to trapping: How to derive it whatever the rate of
      variation of the dynamics.
AB  - In this paper, we investigate the motion of a set of charged particles acted upon
      by a growing electrostatic wave in the limit when the initial wave amplitude is
      vanishingly small and when all the particles have the same initial action, I(0).
      We show, both theoretically and numerically, that when all the particles have
      been trapped in the wave potential, the distribution in action exhibits a very
      sharp peak about the smallest action. Moreover, as the wave keeps growing, the
      most probable action tends toward a constant, I(f), which we estimate
      theoretically. In particular, we show that I(f) may be calculated very accurately
      when the particles' motion before trapping is far from adiabatic by making use of
      a perturbation analysis in the wave amplitude. This fills a gap regarding the
      computation of the action change, which, in the past, has only been addressed for
      slowly varying dynamics. Moreover, when the variations of the dynamics are fast
      enough, we show that the Fourier components of the particles' distribution
      function can be calculated by connecting estimates from our perturbation analysis
      with those obtained by assuming that all the particles have the same constant
      action, I=I(f). This result is used to compute theoretically the imaginary part
      of the electron susceptibility of an electrostatic wave in a plasma. Moreover,
      using our formula for the electron susceptibility, we can extend the range in
      epsilon(a) (the parameter that quantifies the slowness of the dynamics) for our
      perturbative estimate of I(f)-I(0). This range can actually be pushed down to
      values of epsilon(a) allowing the use of neoadiabatic techniques to compute the
      jump in action. Hence, this paper shows that the action change due to trapping
      can be calculated theoretically, regardless of the rate of variation of the
      dynamics, by connecting perturbative results with neoadiabatic ones.

PMID- 25974571
TI  - Equivalence of phase-oscillator and integrate-and-fire models.
AB  - A quantitative comparison of various classes of oscillators (integrate-and-fire,
      Winfree, and Kuramoto-Daido type) is performed in the weak-coupling limit for a
      fully connected network of identical units. An almost perfect agreement is found,
      with only tiny differences among the models. We also show that the regime of self
      consistent partial synchronization is rather general and can be observed for
      arbitrarily small coupling strength in any model class. As a byproduct of our
      study, we are able to show that an integrate-and-fire model with a generic pulse
      shape can be always transformed into a similar model with delta pulses and a
      suitable phase response curve. 

PMID- 25974572
TI  - Structured scale dependence in the Lyapunov exponent of a Boolean chaotic map.
AB  - We report on structures in a scale-dependent Lyapunov exponent of an experimental
      chaotic map that arise due to discontinuities in the map. The chaos is realized
      in an autonomous Boolean network, which is constructed using asynchronous logic
      gates to form a map operator that outputs an unclocked pulse-train of varying
      widths. The map operator executes pulse-width stretching and folding and the
      operator's output is fed back to its input to continuously iterate the map. Using
      a simple model, we show that the structured scale-dependence in the system's
      Lyapunov exponent is the result of the discrete logic elements in the map
      operator's stretching function. 

PMID- 25974573
TI  - Analytical stability boundaries of an injected two-polarization semiconductor
      laser.
AB  - The classical problem of a semiconductor laser subject to polarized injection is
      revisited. From the laser rate equations for the transverse electric (TE) and
      transverse magnetic (TM) modes, we first determine the steady states. We then
      investigate their linear stability properties and derive analytical expressions
      for the steady, saddle-node, and Hopf bifurcation points. We highlight conditions
      for bistability between pure- and mixed-mode steady states for the laser subject
      to either TE or TM injection. To our knowledge, the first case has not been
      documented yet. An important parameter is the ratio of the polarization gain
      coefficients and we explore its effect on the stability and bifurcation diagrams.

PMID- 25974574
TI  - Stability of the flow in a soft tube deformed due to an applied pressure
      gradient.
AB  - A linear stability analysis is carried out for the flow through a tube with a
      soft wall in order to resolve the discrepancy of a factor of 10 for the
      transition Reynolds number between theoretical predictions in a cylindrical tube
      and the experiments of Verma and Kumaran [J. Fluid Mech. 705, 322 (2012)]. Here
      the effect of tube deformation (due to the applied pressure difference) on the
      mean velocity profile and pressure gradient is incorporated in the stability
      analysis. The tube geometry and dimensions are reconstructed from experimental
      images, where it is found that there is an expansion and then a contraction of
      the tube in the streamwise direction. The mean velocity profiles at different
      downstream locations and the pressure gradient, determined using computational
      fluid dynamics, are found to be substantially modified by the tube deformation.
      The velocity profiles are then used in a linear stability analysis, where the
      growth rates of perturbations are calculated for the flow through a tube with the
      wall modeled as a neo-Hookean elastic solid. The linear stability analysis is
      carried out for the mean velocity profiles at different downstream locations
      using the parallel flow approximation. The analysis indicates that the flow first
      becomes unstable in the downstream converging section of the tube where the flow
      profile is more pluglike when compared to the parabolic flow in a cylindrical
      tube. The flow is stable in the upstream diverging section where the deformation
      is maximum. The prediction for the transition Reynolds number is in good
      agreement with experiments, indicating that the downstream tube convergence and
      the consequent modification in the mean velocity profile and pressure gradient
      could reduce the transition Reynolds number by an order of magnitude.

PMID- 25974575
TI  - Three-equation model for the self-similar growth of Rayleigh-Taylor and Richtmyer
      Meskov instabilities.
AB  - In the present work, the two-equation k-L model [G. Dimonte and R. Tipton, Phys.
      Fluids 18, 085101 (2006)] is extended by the addition of a third equation for the
      mass-flux velocity. A set of model constants is derived to satisfy an ansatz of
      self-similarity in the low Atwood number limit. The model is then applied to the
      simulation of canonical Rayleigh-Taylor and Richtmyer-Meshkov test problems in
      one dimension and is demonstrated to reproduce analytical self-similar growth and
      to recover growth rates used to constrain the model.

PMID- 25974576
TI  - Predicting two-dimensional turbulence.
AB  - Prediction is a fundamental objective of science. It is more difficult for
      chaotic and complex systems like turbulence. Here we use information theory to
      quantify spatial prediction using experimental data from a turbulent soap film.
      At high Reynolds number, Re, where a cascade exists, turbulence becomes easier to
      predict as the inertial range broadens. The development of a cascade at low Re is
      also detected. 

PMID- 25974577
TI  - Algebraic instability in shallow water flows with horizontally nonuniform
      density.
AB  - The regimes and mechanisms of the Rayleigh-Taylor instability have been studied
      in the scope of the nonhydrostatic shallow water model with horizontally
      nonuniform density. As analysis shows, the nonhydrostaticity has a crucial
      influence on the instability. It is for this reason that at the final stage a
      collapse tendency predicted on the base of the hydrostatic scenario slows down
      and turns into the regime of algebraic instability. The numerical testing has
      shown that in spite of its simplicity, the model is quite able to describe
      realistically a number of effects. For example, the model captures the shallowing
      effect, which manifests itself as profile concavities on either side of the jet
      coming out of the boundary layer. 

PMID- 25974578
TI  - Localization in a spanwise-extended model of plane Couette flow.
AB  - We consider a nine-partial-differential-equation (1-space and 1-time) model of
      plane Couette flow in which the degrees of freedom are severely restricted in the
      streamwise and cross-stream directions to study spanwise localization in detail.
      Of the many steady Eckhaus (spanwise modulational) instabilities identified of
      global steady states, none lead to a localized state. Spatially localized, time
      periodic solutions were found instead, which arise in saddle node bifurcations in
      the Reynolds number. These solutions appear global (domain filling) in narrow
      (small spanwise) domains yet can be smoothly continued out to fully spanwise
      localized states in very wide domains. This smooth localization behavior, which
      has also been seen in fully resolved duct flow (S. Okino, Ph.D. thesis, Kyoto
      University, Kyoto, 2011), indicates that an apparently global flow structure does
      not have to suffer a modulational instability to localize in wide domains. 

PMID- 25974579
TI  - Instability in stratified accretion flows under primary and secondary
      perturbations.
AB  - We consider horizontal linear shear flow (shear rate denoted by Lambda) under
      vertical uniform rotation (ambient rotation rate denoted by Omega(0)) and
      vertical stratification (buoyancy frequency denoted by N) in unbounded domain. We
      show that, under a primary vertical velocity perturbation and a radial density
      perturbation consisting of a one-dimensional standing wave with frequency N and
      amplitude proportional to w(0)sin(ENx/w(0))~ENx(?1), where x denotes the radial
      coordinate and E a small parameter, a parametric instability can develop in the
      flow, provided N(2)>8Omega(0)(2Omega(0)-Lambda). For astrophysical accretion
      flows and under the shearing sheet approximation, this implies
      N(2)>8Omega(0)(2)(2-q), where q=Lambda/Omega(0) is the local shear gradient. In
      the case of a stratified constant angular momentum disk, q=2, there is a
      parametric instability with the maximal growth rate (sigma(m)/E)=3?[3]/16 for any
      positive value of the buoyancy frequency N. In contrast, for a stratified
      Keplerian disk, q=1.5, the parametric instability appears only for N>2Omega(0)
      with a maximal growth rate that depends on the ratio Omega(0)/N and approaches
      (3?[3]/16)E for large values of N.

PMID- 25974580
TI  - Nanobubbles around plasmonic nanoparticles: Thermodynamic analysis.
AB  - We describe the dynamics of vapor nanobubbles in water, on the basis of
      simulations of a hydrodynamics phase-field model. This situation is relevant to
      recent experiments, where a water nanobubble is generated around a nanoparticle
      immersed in water, and heated by an intense laser pulse. We emphasize the
      importance of nanoscale effects in the dynamics of the nanobubble. We first
      analyze the evolution of the temperature inside the bubble. We show that the
      temperature drops by hundredths of kelvins in a few picoseconds, just after
      nanobubble formation. This is the result of the huge drop of the thermal boundary
      conductance between the nanoparticle and the fluid accompanying vaporization.
      Subsequently, the temperature inside the vapor is almost homogeneous and the
      temperature gradient is concentrated in the liquid, whose thermodynamic state
      locally follows the saturation line. We discuss also the evolution of the
      pressure inside the vapor nanobubble. We show that nanobubble generation is
      accompanied by a pressure wave propagating in the liquid at a velocity close to
      the liquid speed of sound. The internal pressure inside the vapor just after its
      formation largely exceeds Laplace pressure and quickly relaxes as a result of the
      damping generated by the viscous forces. All these considerations shed light on
      the thermodynamics of the nanobubbles generated experimentally. 

PMID- 25974581
TI  - Circularly confined microswimmers exhibit multiple global patterns.
AB  - Geometric confinement plays an important role in the dynamics of natural and
      synthetic microswimmers from bacterial cells to self-propelled particles in high
      throughput microfluidic devices. However, little is known about the effects of
      geometric confinement on the emergent global patterns in such self-propelled
      systems. Recent experiments on bacterial cells report that, depending on the cell
      concentration, cells either spontaneously organize into vortical motion in thin
      cylindrical and spherical droplets or aggregate at the inner boundary of the
      droplets. Our goal in this paper is to investigate, in the context of an
      idealized physical model, the interplay between geometric confinement and level
      of flagellar activity on the emergent collective patterns. We show that
      decreasing flagellar activity induces a hydrodynamically triggered transition in
      confined microswimmers from swirling to global circulation (vortex) to boundary
      aggregation and clustering. These results highlight that the complex interplay
      between confinement, flagellar activity, and hydrodynamic flows in concentrated
      suspensions of microswimmers could lead to a plethora of global patterns that are
      difficult to predict from geometric consideration alone. 

PMID- 25974582
TI  - Prediction of frequencies in thermosolutal convection from mean flows.
AB  - Motivated by studies of the cylinder wake, in which the vortex-shedding frequency
      can be obtained from the mean flow, we study thermosolutal convection driven by
      opposing thermal and solutal gradients. In the archetypal two-dimensional
      geometry with horizontally periodic and vertical no-slip boundary conditions,
      branches of traveling waves and standing waves are created simultaneously by a
      Hopf bifurcation. Consistent with similar analyses performed on the cylinder
      wake, we find that the traveling waves of thermosolutal convection have the RZIF
      property, meaning that linearization about the mean fields of the traveling waves
      yields an eigenvalue whose real part is almost zero and whose imaginary part
      corresponds very closely to the nonlinear frequency. In marked contrast,
      linearization about the mean field of the standing waves yields neither zero
      growth nor the nonlinear frequency. It is shown that this difference can be
      attributed to the fact that the temporal power spectrum for the traveling waves
      is peaked, while that of the standing waves is broad. We give a general
      demonstration that the frequency of any quasimonochromatic oscillation can be
      predicted from its temporal mean. 

PMID- 25974583
TI  - Reduced description of exact coherent states in parallel shear flows.
AB  - A reduced description of exact coherent structures in the transition regime of
      plane parallel shear flows is developed, based on the Reynolds number scaling of
      streamwise-averaged (mean) and streamwise-varying (fluctuation) velocities
      observed in numerical simulations. The resulting system is characterized by an
      effective unit Reynolds number mean equation coupled to linear equations for the
      fluctuations, regularized by formally higher-order diffusion. Stationary coherent
      states are computed by solving the resulting equations simultaneously using a
      robust numerical algorithm developed for this purpose. The algorithm determines
      self-consistently the amplitude of the fluctuations for which the associated mean
      flow is just such that the fluctuations neither grow nor decay. The procedure is
      used to compute exact coherent states of a flow introduced by Drazin and Reid
      [Hydrodynamic Stability (Cambridge University Press, Cambridge, UK, 1981)] and
      studied by Waleffe [Phys. Fluids 9, 883 (1997)]: a linearly stable, plane
      parallel shear flow confined between stationary stress-free walls and driven by a
      sinusoidal body force. Numerical continuation of the lower-branch states to lower
      Reynolds numbers reveals the presence of a saddle node; the saddle node allows
      access to upper-branch states that are, like the lower-branch states, self
      consistently described by the reduced equations. Both lower- and upper-branch
      states are characterized in detail.

PMID- 25974584
TI  - Magnetization directions and geometries of helical microswimmers for linear
      velocity-frequency response.
AB  - Recently, there has been much progress in creating microswimmers or microrobots
      capable of controlled propulsion in fluidic environments. These microswimmers
      have numerous possible applications in biomedicine, microfabrication, and
      sensing. One type of effective microrobot consists of rigid magnetic helical
      microswimmers that are propelled when rotated at a range of frequencies by an
      external rotating magnetic field. Here we focus on investigating which magnetic
      dipoles and helical geometries optimally lead to linear velocity-frequency
      response, which may be desirable for the precise control and positioning of
      microswimmers. We identify a class of optimal magnetic field moments. We connect
      our results to the wobbling behavior previously observed and studied in helical
      microswimmers. In contrast to previous studies, we find that when the full
      helical geometry is taken into account, wobble-free motion is not possible for
      magnetic fields rotating in a plane. Our results compare well quantitatively to
      previously reported experiments, validating the theoretical analysis method.
      Finally, in the context of our optimal moments, we identify helical geometries
      for minimization of wobbling and maximization of swimming velocities. 

PMID- 25974585
TI  - Multirelaxation-time lattice Boltzmann model for droplet heating and evaporation
      under forced convection.
AB  - We investigate the evaporation of a droplet surrounded by superheated vapor with
      relative motion between phases. The evaporating droplet is a challenging process,
      as one must take into account the transport of mass, momentum, and heat. Here a
      lattice Boltzmann method is employed where phase change is controlled by a
      nonideal equation of state. First, numerical simulations are compared to the D(2)
      law for a vaporizing static droplet and good agreement is observed. Results are
      then presented for a droplet in a Lagrangian frame under a superheated vapor
      flow. Evaporation is described in terms of the temperature difference between
      liquid-vapor and the inertial forces. The internal liquid circulation driven by
      surface-shear stresses due to convection enhances the evaporation rate. Numerical
      simulations demonstrate that for higher Reynolds numbers, the dynamics of
      vaporization flux can be significantly affected, which may cause an oscillatory
      behavior on the droplet evaporation. The droplet-wake interaction and local mass
      flux are discussed in detail.

PMID- 25974586
TI  - Energy transfer and dissipation in forced isotropic turbulence.
AB  - A model for the Reynolds-number dependence of the dimensionless dissipation rate
      C(E) was derived from the dimensionless Karman-Howarth equation, resulting in
      C(E)=C(E,infinity)+C/R(L)+O(1/R(L)(2)), where R(L) is the integral scale Reynolds
      number. The coefficients C and C(E,infinity) arise from asymptotic expansions of
      the dimensionless second- and third-order structure functions. This theoretical
      work was supplemented by direct numerical simulations (DNSs) of forced isotropic
      turbulence for integral scale Reynolds numbers up to R(L)=5875 (R(lambda)=435),
      which were used to establish that the decay of dimensionless dissipation with
      increasing Reynolds number took the form of a power law R(L)(n) with exponent
      value n=-1.000+/-0.009 and that this decay of C(E) was actually due to the
      increase in the Taylor surrogate U(3)/L. The model equation was fitted to data
      from the DNS, which resulted in the value C=18.9+/-1.3 and in an asymptotic value
      for C(E) in the infinite Reynolds-number limit of C(E,infinity)=0.468+/-0.006.

PMID- 25974587
TI  - Shell model for buoyancy-driven turbulence.
AB  - In this paper we present a unified shell model for stably stratified and
      convective turbulence. Numerical simulation of this model for stably stratified
      flow shows Bolgiano-Obukhbov scaling in which the kinetic energy spectrum varies
      as k(-11/5). The shell model of convective turbulence yields Kolmogorov's
      spectrum. These results are consistent with the energy flux and energy feed due
      to buoyancy, and are in good agreement with direct numerical simulations of Kumar
      et al. [Phys. Rev. E 90, 023016 (2014)].

PMID- 25974588
TI  - History effects on nonwetting fluid residuals during desaturation flow through
      disordered porous media.
AB  - We investigate experimentally the sweeping of a nonwetting fluid by a wetting one
      in a quasi-two-dimensional porous medium consisting of random obstacles. We focus
      primarily on the resulting phase distributions and the residual nonwetting phase
      saturation as a function of the normalized wetting fluid flow rate-the capillary
      number Ca-at steady state. The wetting liquid is then flowing in the medium
      partially saturated by immobile nonwetting liquid blobs. The decrease of the
      nonwetting saturation is an irreversible process that depends strongly on flow
      history and more specifically on the highest value of Ca reached in the past. At
      lower Ca values, when capillary forces are dominant, the residual steady state
      saturation depends significantly on the initial phase configuration. However, at
      higher Ca, the saturation becomes independent of the history and thus follows a
      master curve that converges to an asymptotic residual value. Blob sizes range
      over four orders of magnitude in our experimental domain, following a probability
      distribution function P that scales with the blob size s as P(s)?s(-2) for blob
      sizes larger than the typical pore size. It also exhibits a maximum size cutoff
      s(max), that decreases as s(max)?Ca(-1). To determine the flow properties, we
      have measured the pressure drop (B) versus the flow rate (Ca). In the ranges of
      low and high Ca values, the relationship between Ca and B is found to be linear,
      following Darcy's law (B?Ca). In the intermediate regime, the progressive
      mobilization of blobs leads to a nonlinear dependence B?Ca(0.65), due to an
      increase of the available flow paths.

PMID- 25974589
TI  - Disentangling inertial waves from eddy turbulence in a forced rotating-turbulence
      experiment.
AB  - We present a spatiotemporal analysis of a statistically stationary rotating
      turbulence experiment, aiming to extract a signature of inertial waves and to
      determine the scales and frequencies at which they can be detected. The analysis
      uses two-point spatial correlations of the temporal Fourier transform of velocity
      fields obtained from time-resolved stereoscopic particle image velocimetry
      measurements in the rotating frame. We quantify the degree of anisotropy of
      turbulence as a function of frequency and spatial scale. We show that this space
      time-dependent anisotropy is well described by the dispersion relation of linear
      inertial waves at large scale, while smaller scales are dominated by the sweeping
      of the waves by fluid motion at larger scales. This sweeping effect is mostly due
      to the low-frequency quasi-two-dimensional component of the turbulent flow, a
      prominent feature of our experiment that is not accounted for by wave-turbulence
      theory. These results question the relevance of this theory for rotating
      turbulence at the moderate Rossby numbers accessible in laboratory experiments,
      which are relevant to most geophysical and astrophysical flows. 

PMID- 25974590
TI  - Three-dimensional transition after wake deflection behind a flapping foil.
AB  - We report the inherently three-dimensional linear instabilities of a propulsive
      wake, produced by a flapping foil, mimicking the caudal fin of a fish or the wing
      of a flying animal. For the base flow, three sequential wake patterns appear as
      we increase the flapping amplitude: Benard-von Karman (BvK) vortex streets;
      reverse BvK vortex streets; and deflected wakes. Imposing a three-dimensional
      spanwise periodic perturbation, we find that the resulting Floquet multiplier
      |MU| indicates an unstable "short wavelength" mode at wave number beta=30, or
      wavelength lambda=0.21 (nondimensionalized by the chord length) at sufficiently
      high flow Reynolds number Re=Uc/nu?600, where U is the upstream flow velocity, c
      is the chord length, and nu is the kinematic viscosity of the fluid. Another,
      "long wavelength" mode at beta=6 (lambda=1.05) becomes critical at somewhat
      higher Reynolds number, although we do not expect that this mode would be
      observed physically because its growth rate is always less than the short
      wavelength mode, at least for the parameters we have considered. The long
      wavelength mode has certain similarities with the so-called mode A in the drag
      wake of a fixed bluff body, while the short wavelength mode appears to have a
      period of the order of twice that of the base flow, in that its structure seems
      to repeat approximately only every second cycle of the base flow. Whether it is
      appropriate to classify this mode as a truly subharmonic mode or as a
      quasiperiodic mode is still an open question however, worthy of a detailed
      parametric study with various flapping amplitudes and frequencies. 

PMID- 25974591
TI  - Stokesian spherical swimmers and active particles.
AB  - The net steady state flow pattern of a distorting sphere is studied in the
      framework of the bilinear theory of swimming at low Reynolds number. It is argued
      that the starting point of a theory of interacting active particles should be
      based on such a calculation, since any arbitrarily chosen steady state flow
      pattern is not necessarily the result of a swimming motion. Furthermore, it is
      stressed that as a rule the phase of stroke is relevant in hydrodynamic
      interactions, so that the net flow pattern must be used with caution. 

PMID- 25974592
TI  - Cusps and cuspidal edges at fluid interfaces: Existence and application.
AB  - One of the intriguing questions in fluid dynamics is on the interrelation between
      dynamic singularities in the solutions of fluid dynamic equations - unboundedness
      of the velocity field in an appropriate norm - and the geometric ones -
      divergence of curvature at fluid interfaces. The present work focuses on two
      generic interfacial singularities - genuine cusps and cuspidal edges - found here
      in both two and three dimensions thus establishing a relation between real fluid
      interfaces and geometric singularity theory. The key finding is the necessary
      condition for the existence of geometric singularities, which is a variation of
      surface tension. It is also established here that the dynamic and geometric
      singularities entail each other only in the case of three-dimensional cusps.
      Explicit asymptotic solutions for the flow field and interface shape near steady
      state singularities at fluid interfaces are developed as well. The practical
      motivation for the present study comes from the fundamental role interfacial
      singularities play in sustaining self-driven conversion of chemical into
      mechanical energy. 

PMID- 25974593
TI  - Dependence of turbulent advection on the Lagrangian correlation time.
AB  - In turbulent scalar mixing, starting from random initial conditions, the root
      mean-square advection term rapidly drops as the flow and the scalar field
      organize. We show first analytically, for the simplified case of a blob in shear
      flow with a finite correlation time, how the advection term is reduced compared
      to a randomly aligned scalar structure. This picture is then generalized to
      turbulent mixing. These examples show that the rapid depletion of advection
      depends on the lifetime of turbulent structures, compared to the local straining
      time scale. A turbulence closure is used to show that the Lagrangian correlation
      time indeed determines the deviation from Gaussian behavior. In particular it is
      shown that in the inertial range the depletion mechanism is self-similar, since a
      constant ratio is observed between the advection spectrum and its Gaussian
      equivalent. Finally, direct numerical simulation shows that in the limit of an
      infinite correlation time of the turbulent eddies, corresponding to a frozen
      velocity field, the mean-square advection tends to a zero fraction of its
      Gaussian estimate. 

PMID- 25974594
TI  - Effect of gravity on clustering patterns and inertial particle attractors in
      kinematic simulations.
AB  - In this paper, we study the clustering of inertial particles using a periodic
      kinematic simulation. The systematic Lagrangian tracking of particles makes it
      possible to identify the particles' clustering patterns for different values of
      particle inertia and drift velocity. The different cases are characterized by
      different pairs of Stokes number (St) and Froude number (Fr). For the present
      study, 0<=St<=1 and 0.4<=Fr<=1.4. The main focus is to identify and then quantify
      the clustering attractor-when it exists-that is the set of points in the physical
      space where the particles settle when time goes to infinity. Depending on the
      gravity effect and inertia values, the Lagrangian attractor can have different
      dimensions, varying from the initial three-dimensional space to two-dimensional
      layers and one-dimensional attractors that can be shifted from a horizontal to a
      vertical position. 

PMID- 25974595
TI  - Time irreversibility of the statistics of a single particle in compressible
      turbulence.
AB  - We investigate time irreversibility from the point of view of a single particle
      in Burgers turbulence. Inspired by the recent work for incompressible flows [Xu
      et al., Proc. Natl. Acad. Sci. USA 111, 7558 (2014)], we analyze the evolution of
      the kinetic energy for fluid markers and use the fluctuations of the
      instantaneous power as a measure of time irreversibility. For short times,
      starting from a uniform distribution of markers, we find the scaling <[E(t)
      E(0)](n)>?t and <p(n)>?Re(n-1) for the power as a function of the Reynolds
      number. Both observations can be explained using the "flight-crash" model,
      suggested by Xu et al. Furthermore, we use a simple model for shocks that
      reproduces the moments of the energy difference, including the pre-factor for
      <E(t)-E(0)>. To complete the single-particle picture for Burgers we compute the
      moments of the Lagrangian velocity difference and show that they are bifractal.
      This arises in a similar manner to the bifractality of Eulerian velocity
      differences. In the above setting, time irreversibility is directly manifest as
      particles eventually end up in shocks. We additionally investigate time
      irreversibility in the long-time limit when all particles are located inside
      shocks and the Lagrangian velocity statistics are stationary. We find the same
      scalings for the power and energy differences as at short times and argue that
      this is also a consequence of rare "flight-crash" events related to shock
      collisions.

PMID- 25974596
TI  - Transient changes in electric fields induced by interaction of ultraintense laser
      pulses with insulator and metal foils: Sustainable fields spanning several
      millimeters.
AB  - The temporal evolutions of electromagnetic fields generated by the interaction
      between ultraintense lasers (1.3*10(18) and 8.2*10(18)W/cm(2)) and solid targets
      at a distance of several millimeters from the laser-irradiated region have been
      investigated by electron deflectometry. For three types of foil targets
      (insulating foil, conductive foil, and insulating foil onto which a metal disk
      was deposited), transient changes in the fields were observed. We found that the
      direction, strength, and temporal evolution of the generated fields differ
      markedly for these three types of targets. The results provide an insight for
      studying the emission dynamics of laser-accelerated fast electrons.

PMID- 25974597
TI  - Anomalous collisional absorption of laser pulses in underdense plasma at low
      temperature.
AB  - In a previous paper [M. Kundu, Phys. Plasmas 21, 013302 (2014)], fractional
      collisional absorption (alpha) of laser light in underdense plasma was studied by
      using a classical scattering model of electron-ion collision frequency nu(ei),
      where total velocity v=?[v(th)(2)+v(0)(2)] (with v(th) and v(0) as the thermal
      and the ponderomotive velocity of an electron) dependent Coulomb logarithm
      lnLambda(v) was shown to be responsible for the anomalous (unconventional)
      increase of nu(ei) and alpha(?nu(ei)) with the laser intensity I(0) up to a
      maximum value about an intensity I(c) in the low temperature (T(e)<15eV) regime
      and a conventional ~I(0)(-3/2) decrease when I(0)?I(c). One may object that the
      anomalous increase in nu(ei) and alpha were partly due to the artifact introduced
      in lnLambda through the maximum cutoff distance b(max)?v. In this work, we show
      similar anomalous increase in nu(ei) and alpha versus I(0) (in the low
      temperature and underdense density regime) with more accurate quantum and
      classical kinetic models of nu(ei) without using lnLambda, but with a proper
      choice of the total velocity dependent inverse cutoff length k(max)?v(2)
      (classical) or k(max)?v (quantum). For a given I(0)<5*10(14)Wcm(-2), nu(ei)
      versus T(e) also exhibits so far unnoticed identical anomalous increase as nu(ei)
      versus I(0), even if the conventional k(max)?v(th)(2) or k(max)?v(th) (without
      v(0)) is chosen. The total velocity dependent k(max) in the kinetic models, as
      proposed here, is found to explain the anomalous increase of alpha with I(0)
      measured in some earlier laser-plasma experiments.

PMID- 25974598
TI  - Cluster virial expansion of the equation of state for hydrogen plasma with e-H(2)
      contributions.
AB  - The equation of state of partially ionized hydrogen plasma is considered with
      special focus on the contribution of the e-H(2) interaction. Traditional
      semiempirical concepts such as the excluded volume are improved using microscopic
      approaches to treat the e-H(2) problem. Within a cluster virial expansion, the
      Beth-Uhlenbeck formula is applied to infer the contribution of bound and
      scattering states to the temperature-dependent second virial coefficient. The
      scattering states are calculated using the phase expansion method for the
      polarization interaction that incorporates experimental data for the e-H(2)
      scattering cross section. We present results for the scattering phase shifts,
      differential scattering cross sections, and the second virial coefficient due to
      the e-H(2) interaction. The influence of this interaction on the composition of
      the partially ionized hydrogen plasma is confined to the parameter range where
      both the H(2) and the free-electron components are abundant.

PMID- 25974599
TI  - Resolving structural transitions in spherical dust clusters.
AB  - Finite systems in confining potentials are known to undergo structural
      transitions similar to phase transitions. However, these systems are
      inhomogeneous, and their "melting" point may depend on the position in the trap
      and vary with the particle number. Focusing on three-dimensional Coulomb systems
      in a harmonic trap a rich physics is revealed: in addition to radial melting we
      demonstrate the existence of intrashell disordering and intershell angular
      melting. Our analysis takes advantage of a novel melting criterion that is based
      on the spatial two- and three-particle distribution functions and the associated
      reduced entropy which can be directly measured in complex plasma experiments. 

PMID- 25974600
TI  - Conductivity of warm dense matter including electron-electron collisions.
AB  - We present an approach that can resolve the controversy with respect to the role
      of electron-electron collisions in calculating the dynamic conductivity of dense
      plasmas. In particular, the dc conductivity is analyzed in the low-density,
      nondegenerate limit where the Spitzer theory is valid and electron-electron
      collisions lead to the well-known reduction in comparison to the result
      considering only electron-ion collisions (Lorentz model). With increasing
      degeneracy, the contribution of electron-electron collisions to the dc
      conductivity is decreasing and can be neglected for the liquid metal domain where
      the Ziman theory is applicable. We give expressions for the effect of electron
      electron collisions in calculating the conductivity in the warm dense matter
      region, i.e., for strongly coupled Coulomb systems at arbitrary degeneracy. 

PMID- 25974601
TI  - Physics of giant electromagnetic pulse generation in short-pulse laser
      experiments.
AB  - In this paper we describe the physical processes that lead to the generation of
      giant electromagnetic pulses (GEMPs) at powerful laser facilities. Our study is
      based on experimental measurements of both the charging of a solid target
      irradiated by an ultra-short, ultra-intense laser and the detection of the
      electromagnetic emission in the GHz domain. An unambiguous correlation between
      the neutralization current in the target holder and the electromagnetic emission
      shows that the source of the GEMP is the remaining positive charge inside the
      target after the escape of fast electrons accelerated by the ultra-intense laser.
      A simple model for calculating this charge in the thick target case is presented.
      From this model and knowing the geometry of the target holder, it becomes
      possible to estimate the intensity and the dominant frequencies of the GEMP at
      any facility. 

PMID- 25974602
TI  - Gigagauss-scale quasistatic magnetic field generation in a snail-shaped target.
AB  - A simple setup for the generation of ultra-intense quasistatic magnetic fields,
      based on the generation of electron currents with a predefined geometry in a
      curved snail (or 'escargot') target, is proposed and analyzed. Particle-in-cell
      simulations and qualitative estimates show that gigagauss scale magnetic fields
      may be obtained with existent laser facilities. The described mechanism of the
      strong magnetic field generation may be useful in a wide range of applications,
      from laboratory astrophysics to magnetized inertial confinement fusion schemes. 

PMID- 25974603
TI  - Pseudorelativistic effects on solitons in quantum semiconductor plasma.
AB  - A theory for nonlinear excitations in quantum plasmas is presented for narrow-gap
      semiconductors by considering the combined effects of quantum and
      pseudorelativity. The system is governed by a coupled Klein-Gordon equation for
      the collective wave functions of the conduction electrons and Poisson's equation
      for the electrostatic potential. This gives a closed system, including the
      effects of charge separation, quantum tunneling, and pseudorelativity. By
      choosing the typical parameters of semiconductor InSb, the quasistationary
      soliton solution, which is a multipeaked dark soliton, is obtained numerically
      and shows depleted electron densities correlated with a localized potential. The
      dynamical simulation result shows that the dark soliton is stable and has a
      multipeaked profile, which is consistent with the quasistationary solution. The
      present model and results may be useful in understanding the nonlinear properties
      of semiconductor plasma on an ultrafast time scale. 

PMID- 25974604
TI  - Solitons and vortices in two-dimensional discrete nonlinear Schrodinger systems
      with spatially modulated nonlinearity.
AB  - We consider a two-dimensional (2D) generalization of a recently proposed model
      [Gligoric et al., Phys. Rev. E 88, 032905 (2013)], which gives rise to bright
      discrete solitons supported by the defocusing nonlinearity whose local strength
      grows from the center to the periphery. We explore the 2D model starting from the
      anticontinuum (AC) limit of vanishing coupling. In this limit, we can construct a
      wide variety of solutions including not only single-site excitations, but also
      dipole and quadrupole ones. Additionally, two separate families of solutions are
      explored: the usual "extended" unstaggered bright solitons, in which all sites
      are excited in the AC limit, with the same sign across the lattice (they
      represent the most robust states supported by the lattice, their 1D counterparts
      being those considered as 1D bright solitons in the above-mentioned work), and
      the vortex cross, which is specific to the 2D setting. For all the existing
      states, we explore their stability (also analytically, when possible). Typical
      scenarios of instability development are exhibited through direct simulations.

PMID- 25974605
TI  - Transient growth in Taylor-Couette flow of a Bingham fluid.
AB  - In this paper we investigate linear transient growth of perturbation energy in
      Taylor-Couette flow of a Bingham fluid. The effects of yield stress on transient
      growth and the structure of the optimal perturbation are mainly considered for
      both the wide-gap case and the narrow-gap case. For this purpose we complement
      the linear stability of this flow subjected to axisymmetric disturbances,
      presented by Landry et al. [M. P. Landry, I. A. Frigaard, and D. M. Martinez, J.
      Fluid Mech. 560, 321 (2006)], with the transient growth characteristics of both
      axisymmetric and nonaxisymmetric perturbations. We obtain the variations of the
      relative amplitude of optimal perturbation with yield stress, analyze the roles
      played by the Coriolis force and the additional stress in the evolution of
      meridional perturbations for the axisymmetric modes, and give the explanations
      for the possible change of the optimal azimuthal mode (featured by the maximum
      optimal energy growth G(opt)) with yield stress. These results might help us in
      the understanding of the effect of fluid rheology on transient growth mechanism
      in vortex flows.

PMID- 25974606
TI  - Simple cubic random-site percolation thresholds for neighborhoods containing
      fourth-nearest neighbors.
AB  - In this paper, random-site percolation thresholds for a simple cubic (SC) lattice
      with site neighborhoods containing next-next-next-nearest neighbors (4NN) are
      evaluated with Monte Carlo simulations. A recently proposed algorithm with low
      sampling for percolation thresholds estimation (Bastas et al., arXiv:1411.5834)
      is implemented for the studies of the top-bottom wrapping probability. The
      obtained percolation thresholds are
      p(C)(4NN)=0.31160(12),p(C)(4NN+NN)=0.15040(12),p(C)(4NN+2NN)=0.15950(12),p(C)(4NN
      3NN)=0.20490(12),p(C)(4NN+2NN+NN)=0.11440(12),p(C)(4NN+3NN+NN)=0.11920(12),p(C)(4
      N+3NN+2NN)=0.11330(12), and p(C)(4NN+3NN+2NN+NN)=0.10000(12), where 3NN, 2NN, and
      NN stand for next-next-nearest neighbors, next-nearest neighbors, and nearest
      neighbors, respectively. As an SC lattice with 4NN neighbors may be mapped onto
      two independent interpenetrated SC lattices but with a lattice constant that is
      twice as large, the percolation threshold p(C)(4NN) is exactly equal to p(C)(NN).
      The simplified method of Bastas et al. allows for uncertainty of the percolation
      threshold value p(C) to be reached, similar to that obtained with the classical
      method but ten times faster.

PMID- 25974607
TI  - Monte Carlo framework for noncontinuous interactions between particles and
      classical fields.
AB  - Particles and fields are standard components in numerical calculations like
      transport simulations in nuclear physics and have well-understood dynamics.
      Still, a common problem is the interaction between particles and fields due to
      their different formal description. Particle interactions are discrete, pointlike
      events while field dynamics is described with continuous partial-differential
      equations of motion. A workaround is the use of effective theories like the
      Langevin equation with the drawback of energy conservation violation. We present
      a method, which allows us to model noncontinuous interactions between particles
      and scalar fields, allowing us to simulate scattering-like interactions which
      exchange discrete "quanta" of energy and momentum between fields and particles
      while obeying energy and momentum conservation and allowing control over
      interaction strengths and times. In this paper we apply this method to different
      model systems, starting with a simple harmonic oscillator, which is damped by
      losing discrete energy quanta. The second and third system consists of an
      oscillator and a one-dimensional field, which are damped via discrete energy loss
      and are coupled to a stochastic force, leading to equilibrium states which
      correspond to statistical Langevin-like systems. The last example is a scalar
      field in (1 + 3) space-time dimensions, which is coupled to a microcanonical
      ensemble of particles by incorporating particle production and annihilation
      processes. Obeying the detailed-balance principle, the system equilibrates to
      thermal and chemical equilibrium with dynamical fluctuations on the fields,
      generated dynamically by the discrete interactions. 

PMID- 25974608
TI  - Enstrophy-based proper orthogonal decomposition for reduced-order modeling of
      flow past a cylinder.
AB  - Here proper orthogonal decomposition (POD) modal decomposition are performed for
      flow past a circular cylinder at supercritical Reynolds numbers by projecting
      this onto instability modes. The important task of modeling a cylinder wake by
      Stuart-Landau (SL) and the Stuart-Landau-Eckhaus (SLE) equation for instability
      modes is discussed, with the latter shown to be more consistent with multimodal
      pictures of POD and instability modes. The difficult task of finding the
      coefficients of the SLE equation is reported by taking a least squares approach
      for the reduced order model (ROM). The important aspect of the ROM is the choice
      of initial condition for the developed SLE equations, as these are stiff ordinary
      differential equations which are very sensitive to the choice of initial
      conditions. An accurate representation of enstrophy-based POD also reveals the
      presence of modes which occur in isolation (in comparison to modes that come in
      pairs) and the traditional approach of treating instability modes by SL or SLE
      equations does not work directly, which also reveals higher frequency variations.
      Quantifying effects of this mode by time-averaged Navier-Stokes equation (NSE)
      fail to show the variation of the phase of these isolated time-varying modes and
      this is captured here using direct numerical simulation (DNS) data by a multitime
      scale approach. A reconstructed 3-mode ROM solution and the disturbance vorticity
      from DNS match globally in the flow. The agreement between 3-mode SLE
      reconstruction and DNS also proves the consistency of the proposed method and
      helps explain the physical nature of the ensuing Hopf bifurcation following an
      instability. 

PMID- 25974609
TI  - Monte Carlo study of coherent scattering effects of low-energy charged particle
      transport in Percus-Yevick liquids.
AB  - We generalize a simple Monte Carlo (MC) model for dilute gases to consider the
      transport behavior of positrons and electrons in Percus-Yevick model liquids
      under highly nonequilibrium conditions, accounting rigorously for coherent
      scattering processes. The procedure extends an existing technique [Wojcik and
      Tachiya, Chem. Phys. Lett. 363, 381 (2002)], using the static structure factor to
      account for the altered anisotropy of coherent scattering in structured material.
      We identify the effects of the approximation used in the original method, and we
      develop a modified method that does not require that approximation. We also
      present an enhanced MC technique that has been designed to improve the accuracy
      and flexibility of simulations in spatially varying electric fields. All of the
      results are found to be in excellent agreement with an independent multiterm
      Boltzmann equation solution, providing benchmarks for future transport models in
      liquids and structured systems.

PMID- 25974610
TI  - Boundary condition for lattice Boltzmann modeling of microscale gas flows with
      curved walls in the slip regime.
AB  - The lattice Boltzmann method (LBM) has been widely used to simulate microgaseous
      flows in recent years. However, it is still a challenging task for LBM to model
      that kind of microscale flow involving complex geometries, owing to the use of
      uniform Cartesian lattices in space. In this work, a boundary condition for
      microflows in the slip regime is developed for LBM in which the shape of a solid
      wall is well considered. The proposed treatment is a combination of the
      Maxwellian diffuse reflection scheme and the simple bounce-back method. A portion
      of each part is determined by the relative position between the boundary node and
      curved walls, which is the key point that distinguishes this method from some
      previous schemes where the smooth curved surface was assumed to be zigzag lines.
      The present curved boundary condition is implemented with the multiple-relaxation
      times model and verified for several established cases, including the plane
      microchannel flow (aligned and inclined), microcylindrical Couette flow, and the
      flow over an inclined microscale airfoil. The numerical results agree well with
      those predicted by the direct simulation Monte Carlo method. 

PMID- 25974611
TI  - Multiple-relaxation-time lattice Boltzmann kinetic model for combustion.
AB  - To probe both the hydrodynamic nonequilibrium (HNE) and thermodynamic
      nonequilibrium (TNE) in the combustion process, a two-dimensional multiple
      relaxation-time (MRT) version of lattice Boltzmann kinetic model (LBKM) for
      combustion phenomena is presented. The chemical energy released in the progress
      of combustion is dynamically coupled into the system by adding a chemical term to
      the LB kinetic equation. Aside from describing the evolutions of the conserved
      quantities, the density, momentum, and energy, which are what the Navier-Stokes
      model describes, the MRT-LBKM presents also a coarse-grained description on the
      evolutions of some nonconserved quantities. The current model works for both
      subsonic and supersonic flows with or without chemical reaction. In this model,
      both the specific-heat ratio and the Prandtl number are flexible, the TNE effects
      are naturally presented in each simulation step. The model is verified and
      validated via well-known benchmark tests. As an initial application, various
      nonequilibrium behaviors, including the complex interplays between various HNEs,
      between various TNEs, and between the HNE and TNE, around the detonation wave in
      the unsteady and steady one-dimensional detonation processes are preliminarily
      probed. It is found that the system viscosity (or heat conductivity) decreases
      the local TNE, but increases the global TNE around the detonation wave, that even
      locally, the system viscosity (or heat conductivity) results in two kinds of
      competing trends, to increase and to decrease the TNE effects. The physical
      reason is that the viscosity (or heat conductivity) takes part in both the
      thermodynamic and hydrodynamic responses. 

PMID- 25974612
TI  - Predicting the structure of fluids with piecewise constant interactions:
      Comparing the accuracy of five efficient integral equation theories.
AB  - We use molecular dynamics simulations to test integral equation theory
      predictions for the structure of fluids of spherical particles with eight
      different piecewise-constant pair-interaction forms comprising a hard core and a
      combination of two shoulders and/or wells. Since model pair potentials like these
      are of interest for discretized or coarse-grained representations of effective
      interactions in complex fluids (e.g., for computationally intensive inverse
      optimization problems), we focus here on assessing how accurately their
      properties can be predicted by analytical or simple numerical closures including
      Percus-Yevick, hypernetted-chain, and reference hypernetted-chain closures and
      first-order mean spherical and modified first-order mean spherical
      approximations. To make quantitative comparisons between the predicted and
      simulated radial distribution functions, we introduce a cumulative structural
      error metric. For equilibrium fluid state points of these models, we find that
      the reference hypernetted-chain closure is the most accurate of the tested
      approximations as characterized by this metric or related thermodynamic
      quantities. 

PMID- 25974613
TI  - Comment on "Temperature-dependent orientational ordering on a spherical surface
      modeled with a lattice spin model".
AB  - In Sec. II of the named paper, the authors study the planar model on a regular
      two-dimensional (square or triangular) lattice and find evidence of an ordering
      transition at finite temperatures in both cases. It is shown that their findings
      do not agree with, and appear to ignore, a number of mathematical results, which
      have been known in the literature for some decades to date, and entail
      orientational disorder at all finite temperatures, as well as the existence of
      the Berezinski-Kosterlitz-Thouless transition. 

PMID- 25974614
TI  - Reply to "Comment on 'Temperature-dependent orientational ordering on a spherical
      surface modeled with a lattice spin model' ".
AB  - In Romano's Comment [Phys. Rev. E 91, 046501 (2015)] on Sec. II of our paper
      [Phys. Rev. E 90, 022502 (2014)], the author suggests that our findings
      concerning the nature of the ordering transition of our modified Lebwohl-Lasher
      model with two-dimensional planar rotators on a planar lattice are inconsistent
      with known mathematical results. We argue in this Reply that our findings are in
      fact in agreement with previous mathematical and simulation results and that the
      criticisms raised by Romano have no impact on the results presented in our paper.

PMID- 25974615
TI  - Efficacy of a microballoon catheter in transarterial chemoembolization of
      hepatocellular carcinoma using miriplatin, a lipophilic anticancer drug: Short
      term results.
AB  - AIM: The goal of the study was to evaluate the efficacy and safety of balloon
      occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma
      (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles.
      METHODS: B-TACE was performed for 62 HCC nodules in 33 patients who could not be
      treated by surgical resection or radiofrequency ablation. All 33 patients had a
      history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a
      historical comparison, we investigated 40 nodules in 28 patients treated by TACE
      using a conventional microcatheter (C-TACE), miriplatin and gelatin particles.
      The therapeutic effect per tumor was compared between the groups based on the
      Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side
      effects were compared based on the Common Terminology Criteria for Adverse Events
      (ver. 4.0). RESULTS: The therapeutic efficacy after 4-12 weeks was evaluated in
      59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these
      nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C
      TACE group. Local efficacy was significantly higher in nodules treated by B-TACE
      than by C-TACE. The side-effects on hepatic function were similar in the two
      groups. CONCLUSION: Our results suggest that B-TACE with miriplatin is a useful
      treatment for hepatocellular carcinoma.

PMID- 25974616
TI  - Therapeutic Challenges in Diabetes Prevention: We Have Not Found the "Exercise
      Pill".
AB  - Type 2 diabetes has become an enormous public health burden, making diabetes
      prevention a pressing issue. While lifestyle modification is the most effective
      preventive strategy, it is resource-intensive and not universally sustainable. We
      review the evidence on pharmacological options for diabetes prevention, in search
      of a medication that is efficacious, easy to adhere to, well tolerated, and cost
      effective. With the exception of metformin, most other drugs have either limited
      efficacy or costly side effects. 

PMID- 25974618
TI  - High quality syngas production from microwave pyrolysis of rice husk with char
      supported metallic catalysts.
AB  - This study aimed to obtain the maximum possible gas yield and the high quality
      syngas production from microwave pyrolysis of rice husk with rice husk char and
      rice husk char-supported metallic (Ni, Fe and Cu) catalysts. The rice husk char
      supported metallic catalysts had developed pore structure and catalytic activity
      for gas productions and tar conversion. The temperature-rising characteristic,
      product yields, properties of gas products and tar conversion mechanisms were
      investigated. It was found that three rice husk char-supported metallic catalysts
      improved the microwave absorption capability and increased heating rate and final
      temperature. Rice husk char-supported Ni catalyst presented most effective
      effects on gas production, e.g. the gas yield is 53.9%, and the volume
      concentration of desired syngas is 69.96%. Rice husk char-supported Ni and Fe
      catalysts played pivotal roles in tar conversion that less heavy compounds can be
      detected along with the reduction of organic compound number. 

PMID- 25974617
TI  - Contribution of PRS3, RPB4 and ZWF1 to the resistance of industrial Saccharomyces
      cerevisiae CCUG53310 and PE-2 strains to lignocellulosic hydrolysate-derived
      inhibitors.
AB  - PRS3, RPB4 and ZWF1 were previously identified as key genes for yeast tolerance
      to lignocellulose-derived inhibitors. To better understand their contribution to
      yeast resistance to the multiple stresses occurring during lignocellulosic
      hydrolysate fermentations, we overexpressed these genes in two industrial
      Saccharomyces cerevisiae strains, CCUG53310 and PE-2, and evaluated their impact
      on the fermentation of Eucalyptus globulus wood and corn cob hydrolysates. PRS3
      overexpression improved the fermentation rate (up to 32%) and productivity (up to
      48%) in different hydrolysates. ZWF1 and RPB4 overexpression did not improve the
      fermentation performance, but their increased expression in the presence of
      acetic acid, furfural and hydroxymethylfurfural was found to contribute to yeast
      adaptation to these inhibitors. This study expands our understanding about the
      molecular mechanisms involved in industrial yeast tolerance to the stresses
      occurring during lignocellulosic bioethanol production and highlights the
      importance of selecting appropriate strain backgrounds/hydrolysates combinations
      when addressing further improvement of these processes. 

PMID- 25974619
TI  - A Woman With Trismus.

PMID- 25974620
TI  - Insulin/poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical
      Properties and Protein Encapsulation.
AB  - Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block
      poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a
      neutral-cationic block polyelectrolyte). The particular cationic-neutral block
      copolymer can complex INS molecules in aqueous media via electrostatic
      interactions. Light-scattering techniques are used to study the complexation
      process and structure of the hybrid nanoparticles in a series of buffers, as a
      function of protein concentration. The physicochemical and structural
      characteristics of the complexes depend on the ionic strength of the aqueous
      medium, while the concentration of PEG-b-PLys was constant through the series of
      solutions. As INS concentration increased the size distribution of the complexes
      decreased, especially at the highest ionic strength. The size/structure of
      complexes diluted in biological medium indicated that the copolymer imparts
      stealth properties and colloidal and biological stability to the complexes,
      features that could in turn affect the clearance properties in vivo. Therefore,
      these studies could be a rational roadmap for designing the optimum
      complexes/effective nanocarriers for proteins and peptides.

PMID- 25974621
TI  - Base-modified NAD and AMP derivatives and their activity against bacterial DNA
      ligases.
AB  - We report the chemical synthesis and conformational analysis of a collection of 2
      , 6- and 8-substituted derivatives of beta-NAD(+) and AMP, and their biochemical
      evaluation against NAD(+)-dependent DNA ligases from Escherichia coli and
      Mycobacterium tuberculosis. Bacterial DNA ligases are validated anti-microbial
      targets, and new strategies for their inhibition are therefore of considerable
      scientific and practical interest. Our study includes several pairs of beta
      NAD(+) and AMP derivatives with the same substitution pattern at the adenine
      base. This has enabled the first direct comparison of co-substrate and inhibitor
      behaviour against bacterial DNA ligases. Our results suggest that an additional
      substituent in position 6 or 8 of the adenine base in beta-NAD(+) is detrimental
      for activity as either co-substrate or inhibitor. In contrast, substituents in
      position 2 are not only tolerated, but appear to give rise to a new mode of
      inhibition, which targets the conformational changes these DNA ligases undergo
      during catalysis. Using a molecular modelling approach, we highlight that these
      findings have important implications for our understanding of ligase mechanism
      and inhibition, and may provide a promising starting point for the rational
      design of a new class of inhibitors against NAD(+)-dependent DNA ligases. 

PMID- 25974622
TI  - Mast cell degranulation inhibits motor patterns of human ileum and sigmoid colon
      in vitro: relevance for postoperative ileus.
AB  - BACKGROUND: Local release of mast cell proteases during gastrointestinal surgery
      is associated with the inhibition of motility and postoperative ileus (POI). We
      determined whether activation of intramuscular mast cell affects the motor
      patterns of the human ileum and colon and whether proteases are involved.
      METHODS: Motor response of ileal and colonic circular muscle strips was measured
      in organ bath. Mast cell degranulation was induced by compound 48/80 (c48/80; 25
      675 MUg/mL). Motor response was quantified as tone, rhythmic phasic contractions
      (RPCs) and contractions to electric field stimulation (EFS; 40 Hz), and
      bethanechol-evoked contractions. Ketotifen (10(-6) mol/L) and a protease
      inhibitor cocktail (P8340) were used to evaluate the role of mast cell mediators.
      KEY RESULTS: (a) c48/80 impaired the spontaneous and the electrically evoked
      motor response in small bowel and colonic strips (sigmoid colon EC50 : 460.0
      MUg/mL for RPCs and 8.9 MUg/mL for electrically evoked contraction amplitudes)
      and bethanechol-evoked contractions. (b) Preincubation with ketotifen (10(-6)
      mol/L, 1 h) prevented the impairment of RPCs and EFS-evoked contractions in the
      sigmoid colon and ileum but not in the right colon. (c) Preincubation with P8340
      also prevented the impairment of contractions in the sigmoid colon but not in the
      ileum or the right colon. CONCLUSIONS & INFERENCES: Mast cell degranulation by
      c48/80 inhibits the spontaneous and the nerve-mediated motor response in the
      human ileum and colon. The effect is partially mediated by mast cell proteases
      and could be relevant in the pathophysiology of POI.

PMID- 25974623
TI  - Pain-related and Psychological Symptoms in Adolescents With Musculoskeletal and
      Sleep Problems.
AB  - OBJECTIVES: Two-thirds of adolescents with chronic musculoskeletal pain report a
      concurrent sleep problem. Both musculoskeletal pain and sleep problems can have
      deleterious effects on physiological and psychological well-being. We explored
      the prevalence of sleep problems and musculoskeletal pain, using data on 3568
      adolescents from the Avon Longitudinal Study of Children. MATERIALS AND METHODS:
      A comprehensive battery of questionnaires was administered to derive clinical
      phenotypes of musculoskeletal pain. Adolescents with single symptoms were
      compared with those reporting both musculoskeletal pain and sleep problems.
      Linear and logistic regression analyses were used to compare groups on pain
      related variables and psychological complaints. The association between
      sociodemographic variables and comorbid musculoskeletal pain and sleep problems
      was assessed using logistic regression. RESULTS: Over half the sample was female
      (n=2076, 58.2%) and the majority of European ancestry (n=3174, 97.7%). Only 5.5%
      (n=196) of participants were identified as having a pain condition, while 21.2%
      (n=749) reported a significant sleep problem, and 2.8% (n=99) reported comorbid
      musculoskeletal pain and sleep problems. Adolescents with comorbid problems
      experienced greater pain intensity and pain-related anxiety. Other psychological
      complaints were also higher in those who experienced concurrent problems,
      including depression, fatigue, concentration, and overall severity of
      psychological symptoms. DISCUSSION: Comorbid sleep and pain problems were
      associated with a higher incidence of pain-related and psychological symptoms.
      Sleep problems may therefore be an important modifiable risk factor for
      alleviating distress in adolescents with musculoskeletal pain.

PMID- 25974627
TI  - Revisiting the Passerini reaction mechanism: existence of the nitrilium,
      organocatalysis of its formation, and solvent effect.
AB  - The Passerini reaction mechanism is revisited using high-level DFT calculations.
      Contrary to the common belief, the nitrilium intermediate is found to be stable
      in solution and its formation is rate-determining. The present results point out
      that this step is catalyzed by a second carboxylic acid molecule, as the
      subsequent Mumm rearrangement is. The solvent effect on the reaction rate was
      investigated. In a protic solvent like methanol, hydrogen bonds are responsible
      of the increasing barrier of the rate-determining step, compared to the commonly
      used solvent, the dichloromethane. 

PMID- 25974625
TI  - Fluorescence labeling of carbonylated lipids and proteins in cells using coumarin
      hydrazide.
AB  - Carbonylation is a generic term which refers to reactive carbonyl groups present
      in biomolecules due to oxidative reactions induced by reactive oxygen species.
      Carbonylated proteins, lipids and nucleic acids have been intensively studied and
      often associated with onset or progression of oxidative stress related disorders.
      In order to reveal underlying carbonylation pathways and biological relevance, it
      is crucial to study their intracellular formation and spatial distribution.
      Carbonylated species are usually identified and quantified in cell lysates and
      body fluids after derivatization using specific chemical probes. However, spatial
      cellular and tissue distribution have been less often investigated. Here, we
      report coumarin-hydrazide, a fluorescent chemical probe for time- and cost
      efficient labeling of cellular carbonyls followed by fluorescence microscopy to
      evaluate their intracellular formation both in time and space. The specificity of
      coumarin-hydrazide was confirmed in time- and dose-dependent experiments using
      human primary fibroblasts stressed with paraquat and compared with conventional
      DNPH-based immunocytochemistry. Both techniques stained carbonylated species
      accumulated in cytoplasm with strong perinuclear clustering. Using a
      complimentary array of analytical methods specificity of coumarin-hydrazide probe
      towards both protein- and lipid-bound carbonyls has been shown. Additionally, co
      distribution of carbonylated species and oxidized phospholipids was demonstrated.

PMID- 25974626
TI  - Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid
      fibroblasts.
AB  - Despite the fact that several natural products (e.g. crude extracts or purified
      compounds) have been found to activate cell antioxidant responses and/or delay
      cellular senescence the effect(s) of small peptides on cell viability and/or
      modulation of protective mechanisms (e.g. the proteostasis network) remain
      largely elusive. We have thus studied a hexapeptide (Hexapeptide-11) of structure
      Phe-Val-Ala-Pro-Phe-Pro (FVAPFP) originally isolated from yeast extracts and
      later synthesized by solid state synthesis to high purity. We show herein that
      Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or
      skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and
      time-dependent activation of proteasome, autophagy, chaperones and antioxidant
      responses related genes. Moreover, it promoted increased nuclear accumulation of
      Nrf2; higher expression levels of proteasomal protein subunits and increased
      proteasome peptidase activities. In line with these findings we noted that
      Hexapeptide-11 conferred significant protection in fibroblasts against oxidative
      stress-mediated premature cellular senescence, while at in vivo skin deformation
      assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was
      found to induce the activity of extracellular MMPs and it also suppressed cell
      migration. Our presented findings indicate that Hexapeptide-11 is a promising
      anti-ageing agent. 

PMID- 25974624
TI  - Thiol redox homeostasis in neurodegenerative disease.
AB  - This review provides an overview of the biochemistry of thiol redox couples and
      the significance of thiol redox homeostasis in neurodegenerative disease. The
      discussion is centred on cysteine/cystine redox balance, the significance of the
      xc(-) cystine-glutamate exchanger and the association between protein thiol redox
      balance and neurodegeneration, with particular reference to Alzheimer's disease,
      Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. The role of
      thiol disulphide oxidoreductases in providing neuroprotection is also discussed. 

PMID- 25974628
TI  - Intramolecular hydrogen bonding stabilizes the nuclearity of complexes. A
      comparative study based on the H-carborane and Me-carborane framework.
AB  - New dinuclear carboranylcarboxylate-bridged and mononuclear copper(ii) compounds
      containing the 1-CO2H-2-H-1,2-closo-C2B10H10 carborane ligand () have been
      synthesized from the previously synthesized dinuclear compound [Cu2(MU
      L)4(THF)2], . Reaction of with CuSO4 in THF leads to the dinuclear compound
      [Cu2(MU-L)4(THF)2], . The reaction of with different terminal pyridyl ligands
      leads to the formation of a series of structurally analogous complexes by
      substitution of the terminal ligand THF (Lt = py, ; p-CF3-py, ; p-CH3-py, ),
      which maintain the structural Cu2(MU-O2CR)4 core in most of the cases except for
      o-(CH3)2-py where a mononuclear compound () is exclusively obtained. In the case
      of and , other dinuclear compounds [Cu2(L)4(Lt)4], and are obtained in lower
      yield. These compounds have been characterized using analytical, spectroscopic
      (NMR, IR, UV-visible) and electrochemical techniques (CV, DPV). X-ray analysis
      revealed a paddle-wheel structure for the main dinuclear compounds with a square
      pyramidal geometry around each copper ion and the carboranylcarboxylate ions
      bridging two copper atoms in syn-syn mode. In the case of and there are two
      carboranylcarboxylate ions bridging the copper atoms in syn-anti mode whereas the
      other two adopt a monodentate coordination mode. The mononuclear complex obtained
      with the o-(CH3)-py ligand presents a square-planar structure, in which the
      carboranylcarboxylate ligand adoptsmonodentate coordination. The effect of the
      substituent group on the cluster of the carboranylcarboxylate ligands on the
      reactivity of compound is also discussed. 

PMID- 25974630
TI  - FuncTree: Functional Analysis and Visualization for Large-Scale Omics Data.
AB  - Exponential growth of high-throughput data and the increasing complexity of omics
      information have been making processing and interpreting biological data an
      extremely difficult and daunting task. Here we developed FuncTree
      (http://bioviz.tokyo/functree), a web-based application for analyzing and
      visualizing large-scale omics data, including but not limited to genomic,
      metagenomic, and transcriptomic data. FuncTree allows user to map their omics
      data onto the "Functional Tree map", a predefined circular dendrogram, which
      represents the hierarchical relationship of all known biological functions
      defined in the KEGG database. This novel visualization method allows user to
      overview the broad functionality of their data, thus allowing a more accurate and
      comprehensive understanding of the omics information. FuncTree provides extensive
      customization and calculation methods to not only allow user to directly map
      their omics data to identify the functionality of their data, but also to compute
      statistically enriched functions by comparing it to other predefined omics data.
      We have validated FuncTree's analysis and visualization capability by mapping pan
      genomic data of three different types of bacterial genera, metagenomic data of
      the human gut, and transcriptomic data of two different types of human cell
      expression. All three mapping strongly confirms FuncTree's capability to analyze
      and visually represent key functional feature of the omics data. We believe that
      FuncTree's capability to conduct various functional calculations and visualizing
      the result into a holistic overview of biological function, would make it an
      integral analysis/visualization tool for extensive omics base research. 

PMID- 25974631
TI  - The Active Sites of a Rod-Shaped Hollandite DeNOx Catalyst.
AB  - The identification of catalytically active sites (CASs) in heterogeneous
      catalysis is of vital importance to design and develop improved catalysts, but
      remains a great challenge. The CASs have been identified in the low-temperature
      selective catalytic reduction of nitrogen oxides by ammonia (SCR) over a
      hollandite manganese oxide (HMO) catalyst with a rod-shaped morphology and one
      dimensional tunnels. Electron microscopy and synchrotron X-ray diffraction
      determine the surface and crystal structures of the one-dimensional HMO rods
      closed by {100} side facets and {001} top facets. A combination of X-ray
      absorption spectra, molecular probes with potassium and nitric oxide, and
      catalytic tests reveals that the CASs are located on the {100} side facets of the
      HMO rods rather than on the top facets or in the tunnels, and hence semi-tunnel
      structural motifs on the {100} facets are evidenced to be the CASs of the SCR
      reaction. This work paves the way to further investigate the intrinsic mechanisms
      of SCR reactions. 

PMID- 25974632
TI  - Norovirus outbreak associated with a natural lake used for recreation - Oregon,
      2014.
AB  - In July 2014, Multnomah County public health officials investigated a norovirus
      outbreak among persons visiting Blue Lake Regional Park in Oregon. During the
      weekend of the reported illnesses (Friday, July 11-Sunday, July 13) approximately
      15,400 persons visited the park. The investigation identified 65 probable and
      five laboratory-confirmed cases of norovirus infection (70 total cases). No
      hospitalizations or deaths were reported. Analyses from a retrospective cohort
      study revealed that swimming at Blue Lake during July 12-13 was significantly
      associated with illness during July 13-14 (adjusted relative risk = 2.3; 95%
      confidence interval [CI] = 1.1-64.9). Persons who swam were more than twice as
      likely to become ill compared with those who did not swim in the lake. To control
      the outbreak, Blue Lake was closed for 10 days to prevent further illness. This
      investigation underscores the need for guidance for determining when to reopen
      untreated recreational water venues (e.g., lakes) associated with outbreaks, and
      communication tools to inform the public about the risks associated with swimming
      in untreated recreational water venues and measures that can prevent illness. 

PMID- 25974633
TI  - Decrease in rate of opioid analgesic overdose deaths - Staten Island, New York
      City, 2011-2013.
AB  - From 2000 to 2011, the rate of unintentional drug poisoning (overdose) deaths
      involving opioid analgesics increased 435% in Staten Island, from 2.0 to 10.7 per
      100,000 residents. During 2005-2011, disparities widened between Staten Island
      and the other four New York City (NYC) boroughs (Bronx, Brooklyn, Manhattan, and
      Queens); in 2011, the rate in Staten Island was 3.0-4.5 times higher than in the
      other boroughs. In response, the NYC Department of Health and Mental Hygiene
      (DOHMH) implemented a comprehensive five-part public health strategy, with both
      citywide and Staten Island-targeted efforts: 1) citywide opioid prescribing
      guidelines, 2) a data brief for local media highlighting Staten Island mortality
      and prescribing data, 3) Staten Island town hall meetings convened by the NYC
      commissioner of health and meetings with Staten Island stakeholders, 4) a Staten
      Island campaign to promote prescribing guidelines, and 5) citywide airing of
      public service announcements with additional airing in Staten Island.
      Concurrently, the New York state legislature enacted the Internet System for
      Tracking Over-Prescribing (I-STOP), a law requiring prescribers to review the
      state prescription monitoring system before prescribing controlled substances.
      This report describes a 29% decline in the opioid analgesic-involved overdose
      death rate in Staten Island from 2011 to 2013, while the rate did not change in
      the other four NYC boroughs, and compares opioid analgesic prescribing data for
      Staten Island with data for the other boroughs. Targeted public health
      interventions might be effective in lowering opioid analgesic-involved overdose
      mortality rates. 

PMID- 25974629
TI  - HaloTag technology: a versatile platform for biomedical applications.
AB  - Exploration of protein function and interaction is critical for discovering links
      among genomics, proteomics, and disease state; yet, the immense complexity of
      proteomics found in biological systems currently limits our investigational
      capacity. Although affinity and autofluorescent tags are widely employed for
      protein analysis, these methods have been met with limited success because they
      lack specificity and require multiple fusion tags and genetic constructs. As an
      alternative approach, the innovative HaloTag protein fusion platform allows
      protein function and interaction to be comprehensively analyzed using a single
      genetic construct with multiple capabilities. This is accomplished using a
      simplified process, in which a variable HaloTag ligand binds rapidly to the
      HaloTag protein (usually linked to the protein of interest) with high affinity
      and specificity. In this review, we examine all current applications of the
      HaloTag technology platform for biomedical applications, such as the study of
      protein isolation and purification, protein function, protein-protein and protein
      DNA interactions, biological assays, in vitro cellular imaging, and in vivo
      molecular imaging. In addition, novel uses of the HaloTag platform are briefly
      discussed along with potential future applications. 

PMID- 25974634
TI  - Preliminary incidence and trends of infection with pathogens transmitted commonly
      through food - Foodborne Diseases Active Surveillance Network, 10 U.S. sites,
      2006-2014.
AB  - Foodborne illnesses represent a substantial, yet largely preventable, health
      burden in the United States. In 10 U.S. geographic areas, the Foodborne Diseases
      Active Surveillance Network (FoodNet) monitors the incidence of laboratory
      confirmed infections caused by nine pathogens transmitted commonly through food.
      This report summarizes preliminary 2014 data and describes changes in incidence
      compared with 2006-2008 and 2011-2013. In 2014, FoodNet reported 19,542
      infections, 4,445 hospitalizations, and 71 deaths. The incidence of Shiga toxin
      producing Escherichia coli (STEC) O157 and Salmonella enterica serotype
      Typhimurium infections declined in 2014 compared with 2006-2008, and the
      incidence of infection with Campylobacter, Vibrio, and Salmonella serotypes
      Infantis and Javiana was higher. Compared with 2011-2013, the incidence of STEC
      O157 and Salmonella Typhimurium infections was lower, and the incidence of STEC
      non-O157 and Salmonella serotype Infantis infections was higher in 2014. Despite
      ongoing food safety efforts, the incidence of many infections remains high,
      indicating that further prevention measures are needed to make food safer and
      achieve national health objectives.

PMID- 25974635
TI  - Controlling the last known cluster of Ebola virus disease - Liberia, January
      February 2015.
AB  - As one of the three West African countries highly affected by the 2014-2015 Ebola
      virus disease (Ebola) epidemic, Liberia reported approximately 10,000 cases. The
      Ebola epidemic in Liberia was marked by intense urban transmission, multiple
      community outbreaks with source cases occurring in patients coming from the urban
      areas, and outbreaks in health care facilities (HCFs). This report, based on data
      from routine case investigations and contact tracing, describes efforts to stop
      the last known chain of Ebola transmission in Liberia. The index patient became
      ill on December 29, 2014, and the last of 21 associated cases was in a patient
      admitted into an Ebola treatment unit (ETU) on February 18, 2015. The chain of
      transmission was stopped because of early detection of new cases; identification,
      monitoring, and support of contacts in acceptable settings; effective triage
      within the health care system; and rapid isolation of symptomatic contacts. In
      addition, a "sector" approach, which divided Montserrado County into geographic
      units, facilitated the ability of response teams to rapidly respond to community
      needs. In the final stages of the outbreak, intensive coordination among partners
      and engagement of community leaders were needed to stop transmission in densely
      populated Montserrado County. A companion report describes the efforts to enhance
      infection prevention and control efforts in HCFs. After February 19, no
      additional clusters of Ebola cases have been detected in Liberia. On May 9, the
      World Health Organization declared the end of the Ebola outbreak in Liberia.

PMID- 25974636
TI  - Initiation of a ring approach to infection prevention and control at non-Ebola
      health care facilities - Liberia, January-February 2015.
AB  - From mid-January to mid-February 2015, all confirmed Ebola virus disease (Ebola)
      cases that occurred in Liberia were epidemiologically linked to a single index
      patient from the St. Paul Bridge area of Montserrado County. Of the 22 confirmed
      patients in this cluster, eight (36%) sought and received care from at least one
      of 10 non-Ebola health care facilities (HCFs), including clinics and hospitals in
      Montserrado and Margibi counties, before admission to an Ebola treatment unit.
      After recognition that three patients in this emerging cluster had received care
      from a non-Ebola treatment unit, and in response to the risk for Ebola
      transmission in non-Ebola treatment unit health care settings, a focused
      infection prevention and control (IPC) rapid response effort for the immediate
      area was developed to target facilities at increased risk for exposure to a
      person with Ebola (Ring IPC). The Ring IPC approach, which provided rapid,
      intensive, and short-term IPC support to HCFs in areas of active Ebola
      transmission, was an addition to Liberia's proposed longer term national IPC
      strategy, which focused on providing a comprehensive package of IPC training and
      support to all HCFs in the country. This report describes possible health care
      worker exposures to the cluster's eight patients who sought care from an HCF and
      implementation of the Ring IPC approach. On May 9, 2015, the World Health
      Organization (WHO) declared the end of the Ebola outbreak in Liberia. 

PMID- 25974637
TI  - Prevalence and impact on survival of hepatopulmonary syndrome and cirrhotic
      cardiomyopathy in a cohort of cirrhotic patients.
AB  - BACKGROUND & AIMS: Extrahepatic complications of cirrhosis increase the risk for
      decompensation of the liver disease and death. Previous studies show common
      pathogenetic mechanisms involved in the development of hepatopulmonary syndrome
      and cirrhotic cardiomyopathy. We aimed to assess the link between these entities
      and their effect on disease-related patient morbidity and mortality. METHODS:
      Seventy-four consecutive cirrhotic patients without prior history of
      cardiovascular and pulmonary disease were included in a prospective observational
      study. Routine blood work, arterial blood gas analysis, pulse oximetry
      measurements, N-terminal pro-brain natriuretic peptide levels and contrast
      enhanced echocardiography examination with tissue Doppler imaging were performed
      in all patients. Patients were followed up for a median of 6 months and disease
      related adverse events and death were the main outcomes tested. Statistical
      analysis was conducted according to the presence of hepatopulmonary syndrome or
      cirrhotic cardiomyopathy. RESULTS: Hepatopulmonary syndrome was diagnosed in 17
      patients (23%) and cirrhotic cardiomyopathy in 30 patients (40.5%). There was no
      association between the presence of cirrhotic cardiomyopathy and the existence of
      mild or moderate hepatopulmonary syndrome. No echocardiographic parameters were
      useful in predicting the presence of hepatopulmonary syndrome. N-terminal pro
      brain natriuretic peptide levels and length of QT interval did not aid in
      diagnosis of cirrhotic cardiomyopathy. Neither entity had significant influence
      on disease-related outcomes in the follow-up period. CONCLUSIONS: Hepatopulmonary
      syndrome and cirrhotic cardiomyopathy are independent complications arising in
      cirrhosis and have a limited influence on morbidity and mortality on a pre-liver
      transplantation population.

PMID- 25974639
TI  - Soft X-Ray Microscopy Radiation Damage On Fixed Cells Investigated With
      Synchrotron Radiation FTIR Microscopy.
AB  - Radiation damage of biological samples remains a limiting factor in high
      resolution X-ray microscopy (XRM). Several studies have attempted to evaluate the
      extent and the effects of radiation damage, proposing strategies to minimise or
      prevent it. The present work aims to assess the impact of soft X-rays on formalin
      fixed cells on a systematic manner. The novelty of this approach resides on
      investigating the radiation damage not only with XRM, as often reported in
      relevant literature on the topic, but by coupling it with two additional
      independent non-destructive microscopy methods: Atomic Force Microscopy (AFM) and
      FTIR Microscopy (FTIRM). Human Embryonic Kidney 293 cells were exposed to
      different radiation doses at 1 keV. In order to reveal possible morphological and
      biochemical changes, the irradiated cells were systematically analysed with AFM
      and FTIRM before and after. Results reveal that while cell morphology is not
      substantially affected, cellular biochemical profile changes significantly and
      progressively when increasing dose, resulting in a severe breakdown of the
      covalent bonding network. This information impacts most soft XRM studies on fixed
      cells and adds an in-depth understanding of the radiation damage for developing
      better prevention strategies. 

PMID- 25974638
TI  - Report of a case of Raine syndrome and literature review.
AB  - We report on a case of Raine syndrome with a mutation in FAM20C and typical
      phenotypic features consisting of midface hypoplasia, hypoplastic nose, choanal
      atresia, wide fontanelle, exophthalmos, generalized osteosclerosis and
      intracranial calcification. New features in our patient are cerebellar hypoplasia
      and pachygyria. We review the literature and conclude that the triad of
      hypoplastic nose, exophthalmos and generalized osteosclerosis and/or intracranial
      calcification is consistent in all molecularly confirmed cases.

PMID- 25974640
TI  - Efficacy and safety of LY2963016 insulin glargine compared with insulin glargine
      (Lantus(r)) in patients with type 1 diabetes in a randomized controlled trial:
      the ELEMENT 1 study.
AB  - AIMS: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar)
      and the reference product (Lantus(r)) insulin glargine (IGlar) in patients with
      type 1 diabetes (T1D). METHODS: This phase III, randomized, open-label, 52-week
      study enrolled patients with T1D [glycated haemoglobin (HbA1c) <=11%] being
      treated with basal (once-daily) and bolus insulin. Patients were randomized to
      receive once-daily LY IGlar (n = 268) or IGlar (n = 267) in combination with
      mealtime insulin lispro for 52 weeks. The primary efficacy outcome was to test
      the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar as measured
      by change in HbA1c from baseline to 24 weeks. RESULTS: Both treatment groups had
      similar and significant (p < 0.001) within-group decreases in mean HbA1c values
      from baseline. LY IGlar met the non-inferiority criteria compared with IGlar for
      change in HbA1c from baseline to 24 weeks [-0.35 vs -0.46%, least-squares mean
      difference 0.108% (95% confidence interval -0.002 to 0.219), p > 0.05]. There
      were no significant (p > 0.05) treatment differences in other efficacy measures,
      including proportion of patients reaching HbA1c <7%, daily mean blood glucose,
      and insulin dose at 24 and 52 weeks. At 52 weeks, similar findings were observed
      between LY IGlar and IGlar for safety outcomes, including adverse events,
      allergic reactions, hypoglycaemia, weight change and insulin antibodies.
      CONCLUSIONS: Both LY IGlar and IGlar, when used in combination with mealtime
      insulin lispro, provided effective and similar glucose control and similar safety
      profiles.

PMID- 25974641
TI  - Assessing the performance of four different categories of histological criteria
      in brain tumours grading by means of a computer-aided diagnosis image analysis
      system.
AB  - Brain tumours are considered one of the most lethal and difficult to treat forms
      of cancer, with unknown aetiology and lack of any realistic screening. In this
      study, we examine, whether the combination of descriptive criteria, used by
      expert histopathologists in assessing histologic tissue samples, and quantitative
      image analysis features may improve the diagnostic accuracy of brain tumour
      grading. Data comprised 61 cases of brain cancers (astrocytomas,
      oligodendrogliomas, meningiomas) collected from the archives of the University
      Hospital of Patras, Greece. Incorporating physician's descriptive criteria and
      image analysis's quantitative features into a discriminant function, a computer
      aided diagnosis system was designed for discriminating low-grade from high-grade
      brain tumours. Physician's descriptive features, when solely used in the system,
      proved of high discrimination accuracy (93.4%). When verbal descriptive features
      were combined with quantitative image analysis features in the system,
      discrimination accuracy improved to 98.4%. The generalization of the proposed
      system to unseen data converged to an overall prediction accuracy of 86.7% +/-
      5.4%. Considering that histological grading affects treatment selection and
      diagnostic errors may be notable in clinical practice, the utilization of the
      proposed system may safeguard against diagnostic misinterpretations in every day
      clinical practice. 

PMID- 25974642
TI  - Clinically suspected recurrence of gastric carcinoid proved to be
      hypocomplementaemic urticarial vasculitis syndrome with pulmonary involvement.

PMID- 25974643
TI  - Motorcycle helmets: What about their coating?
AB  - In traffic accidents involving motorcycles, paint traces can be transferred from
      the rider's helmet or smeared onto its surface. These traces are usually in the
      form of chips or smears and are frequently collected for comparison purposes.
      This research investigates the physical and chemical characteristics of the
      coatings found on motorcycles helmets. An evaluation of the similarities between
      helmet and automotive coating systems was also performed.Twenty-seven helmet
      coatings from 15 different brands and 22 models were considered. One sample per
      helmet was collected and observed using optical microscopy. FTIR spectroscopy was
      then used and seven replicate measurements per layer were carried out to study
      the variability of each coating system (intravariability). Principal Component
      Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were also performed on the
      infrared spectra of the clearcoats and basecoats of the data set. The most common
      systems were composed of two or three layers, consistently involving a clearcoat
      and basecoat. The coating systems of helmets with composite shells systematically
      contained a minimum of three layers. FTIR spectroscopy results showed that
      acrylic urethane and alkyd urethane were the most frequent binders used for
      clearcoats and basecoats. A high proportion of the coatings were differentiated
      (more than 95%) based on microscopic examinations. The chemical and physical
      characteristics of the coatings allowed the differentiation of all but one pair
      of helmets of the same brand, model and color. Chemometrics (PCA and HCA)
      corroborated classification based on visual comparisons of the spectra and
      allowed the study of the whole data set at once (i.e., all spectra of the same
      layer). Thus, the intravariability of each helmet and its proximity to the others
      (intervariability) could be more readily assessed. It was also possible to
      determine the most discriminative chemical variables based on the study of the
      PCA loadings. Chemometrics could therefore be used as a complementary decision
      making tool when many spectra and replicates have to be taken into account.
      Similarities between automotive and helmet coating systems were highlighted, in
      particular with regard to automotive coating systems on plastic substrates
      (microscopy and FTIR). However, the primer layer of helmet coatings was shown to
      differ from the automotive primer. If the paint trace contains this layer, the
      risk of misclassification (i.e., helmet versus vehicle) is reduced. Nevertheless,
      a paint examiner should pay close attention to these similarities when analyzing
      paint traces, especially regarding smears or paint chips presenting an incomplete
      layer system. 

PMID- 25974644
TI  - New Tetracopper(II) Cubane Cores Driven by a Diamino Alcohol: Self-assembly
      Synthesis, Structural and Topological Features, and Magnetic and Catalytic
      Oxidation Properties.
AB  - Two new coordination compounds with tetracopper(II) cores, namely, a 1D
      coordination polymer, [Cu4(MU4-H2edte)(MU5-H2edte)(sal)2]n.10nH2O (1), and a
      discrete 0D tetramer, [Cu4(MU4-Hedte)2(Hpmal)2(H2O)].7.5H2O (2), were easily self
      assembled from aqueous solutions of copper(II) nitrate, N,N,N',N'-tetrakis(2
      hydroxyethyl)ethylenediamine (H4edte), salicylic acid (H2sal), or phenylmalonic
      acid (H2pma). The obtained compounds were characterized by IR and electron
      paramagnetic resonance spectroscopy, thermogravimetric and elemental analysis,
      and single-crystal X-ray diffraction. In addition to different dimensionalities,
      their structures reveal distinct single-open [Cu4(MU2-O)(MU3-O)3] (in 1) or
      double-open [Cu4(MU2-O)2(MU3-O)2] (in 2) cubane cores with 3M4-1 topology. In
      crystal structures, numerous crystallization water molecules are arranged into
      the intricate infinite 1D {(H2O)18}n water tapes (in 1) or discrete (H2O)9
      clusters (in 2) that participate in multiple hydrogen-bonding interactions with
      the metal-organic hosts, thus extending the overall structures into very complex
      3D supramolecular networks. After simplification, their topological analysis
      revealed the binodal 6,10- or 6,8-connected underlying 3D nets with unique or
      rare 6,8T2 topology in 1 and 2, respectively. The magnetic properties of 1 and 2
      were investigated in the 1.8-300 K temperature range, indicating overall
      antiferromagnetic interactions between the adjacent Cu(II) ions within the
      [Cu4O4] cores. The obtained compounds also act as bioinspired precatalysts for
      mild homogeneous oxidation, by aqueous hydrogen peroxide at 50  degrees C in an
      acidic MeCN/H2O medium, of various cyclic and linear C5-C8 alkanes to the
      corresponding alcohols and ketones. Overall product yields of up to 21% (based on
      alkane) were achieved, and the effects of various reaction parameters were
      studied. 

PMID- 25974645
TI  - Breast implant-associated anaplastic large cell lymphoma in a patient with Li
      Fraumeni syndrome.

PMID- 25974648
TI  - New pigmented lesion over a site of tumor treatment.

PMID- 25974649
TI  - Chloroquine retinopathy.

PMID- 25974651
TI  - Omission in article information.

PMID- 25974650
TI  - Incorrect data in abstract and table.

PMID- 25974652
TI  - Error in byline.

PMID- 25974653
TI  - Rational Drug Development for Mucous Dehydration and Mucous Metaplasia.
AB  - Airway diseases that are clinically characterized by mucous hypersecretion are
      associated with dehydrated secretions and impaired mucociliary clearance. The
      failure to clear pro-inflammatory proteases can further exacerbate the mucous
      dehydration, giving rise to a positive feedback loop that produces a mucous
      metaplasia and lung remodeling. Increased understanding of the complex mechanisms
      that regulate airway hydration in health and disease is a prerequisite for
      rational design of novel therapies. Clinical trials of aerosolized osmolytes and
      of modulators of epithelial ion channels have provided support for the hypothesis
      that correcting mucus hydration improves clinical benefit, with the caveat that
      many of these agents have direct mucolytic properties that are likely to be
      synergistic with enhanced hydration.

PMID- 25974654
TI  - Metrology of confined flows using wide field nanoparticle velocimetry.
AB  - The manipulation of fluids in micro/nanofabricated systems opens new avenues to
      engineer the transport of matter at the molecular level. Yet the number of
      methods for the in situ characterization of fluid flows in shallow channels is
      limited. Here we establish a simple method called nanoparticle velocimetry
      distribution analysis (NVDA) that relies on wide field microscopy to measure the
      flow rate and channel height based on the fitting of particle velocity
      distributions along and across the flow direction. NVDA is validated by
      simulations, showing errors in velocity and height determination of less than 1%
      and 8% respectively, as well as with experiments, in which we monitor the
      behavior of 200 nm nanoparticles conveyed in channels of ~1.8 MUm in height. We
      then show the relevance of this assay for the characterization of flows in
      bulging channels, and prove its suitability to characterize the concentration of
      particles across the channel height in the context of visco-elastic focusing. Our
      method for rapid and quantitative flow characterization has therefore a broad
      spectrum of applications in micro/nanofluidics, and a strong potential for the
      optimization of Lab-on-Chips modules in which engineering of confined transport
      is necessary. 

PMID- 25974655
TI  - Novel Potent Orthosteric Antagonist of ASIC1a Prevents NMDAR-Dependent LTP
      Induction.
AB  - Acid sensing ion channels 1a (ASIC1a) are of crucial importance in numerous
      physiological and pathological processes in the brain. Here we demonstrate that
      novel 2-oxo-2H-chromene-3-carboxamidine derivative 5b, designed with molecular
      modeling approach, inhibits ASIC1a currents with an apparent IC50 of 27 nM when
      measured at pH 6.7. Acidification to 5.0 decreases the inhibition efficacy by up
      to 3 orders of magnitude. The 5b molecule not only shifts pH dependence of ASIC1a
      activation but also inhibits its maximal evoked response. These findings suggest
      that compound 5b binds to pH sensor of ASIC1a acting as orthosteric
      noncompetitive antagonist. At 100 nM, compound 5b completely inhibits induction
      of long-term potentiation (LTP) in CA3-CA1 but not in MF-CA3 synapses. These
      findings support the knockout data indicating the crucial modulatory role of
      ASIC1a channels in the NMDAR-dependent LTP and introduce a novel type of ASIC1a
      antagonists. 

PMID- 25974656
TI  - Multilocus Sequence Typing of Cronobacter Strains Isolated from Retail Foods and
      Environmental Samples.
AB  - Cronobacter spp. are bacterial pathogens that affect children and
      immunocompromised adults. In this study, we used multilocus sequence typing
      (MLST) to determine sequence types (STs) in 11 Cronobacter spp. strains isolated
      from retail foods, 29 strains from dust samples obtained from vacuum cleaners,
      and 4 clinical isolates. Using biochemical tests, species-specific polymerase
      chain reaction, and MLST analysis, 36 strains were identified as Cronobacter
      sakazakii, and 6 were identified as Cronobacter malonaticus. In addition, one
      strain that originated from retail food and one from a dust sample from a vacuum
      cleaner were identified on the basis of MLST analysis as Cronobacter dublinensis
      and Cronobacter turicensis, respectively. Cronobacter spp. strains isolated from
      the retail foods were assigned to eight different MLST sequence types, seven of
      which were newly identified. The strains isolated from the dust samples were
      assigned to 7 known STs and 14 unknown STs. Three clinical isolates and one
      household dust isolate were assigned to ST4, which is the predominant ST
      associated with neonatal meningitis. One clinical isolate was classified based on
      MLST analysis as Cronobacter malonaticus and belonged to an as-yet-unknown ST.
      Three strains isolated from the household dust samples were assigned to ST1,
      which is another clinically significant ST. It can be concluded that Cronobacter
      spp. strains of different origin are genetically quite variable. The recovery of
      C. sakazakii strains belonging to ST1 and ST4 from the dust samples suggests the
      possibility that contamination could occur during food preparation. All of the
      novel STs and alleles for C. sakazakii, C. malonaticus, C. dublinensis, and C.
      turicensis determined in this study were deposited in the Cronobacter MLST
      database available online ( http://pubmlst.org/cronobacter/).

PMID- 25974658
TI  - Erratum.

PMID- 25974657
TI  - Understanding the Wii Exergames Use: Voices from Assisted Living Residents.
AB  - PURPOSE: The study was to understand the facilitators and barriers to exercise
      using exergames among assisted living residents, particularly in the area of
      cognitive, physical, and psychosocial effects. DESIGN: Self-efficacy theory was
      incorporated into the design of the Wii Fit exergaming program. METHOD: Fifteen
      participants (mean age: 87.07 +/- 3.92) received the program twice a week for 4
      weeks. Semi-structural individual interview was conducted after the program.
      Interview responses were analyzed using basic content analysis methods. FINDINGS:
      Five themes emerged that facilitated participants? desire to exercise: (1) health
      and mobility; (2) increased alertness; (3) elevated mindset; (4) social
      interaction; and (5) structured program. Barriers to engage in exercise included:
      (1) age- or health-related impairments to exercise; and (2) unpleasant
      experiences related to exercise. CONCLUSIONS: An intervention incorporating self
      efficacy and Wii exergames did result in the identification of cognitive,
      physical, and psychosocial benefits and barriers to exercise.

PMID- 25974659
TI  - Magnetic core-shell CuFe2O4@C3N4 hybrids for visible light photocatalysis of
      Orange II.
AB  - Novel CuFe2O4@C3N4 core-shell photocatalysts were fabricated through a self
      assembly method and characterized by X-ray diffraction, Fourier transform
      infrared spectroscopy, thermogravimetric analysis, X-ray photoelectron
      spectroscopy, transmission electron microscopy and Uv-vis diffuse reflection
      spectroscopy. The photocatalytic performances of the CuFe2O4@C3N4 catalysts were
      evaluated in photo Fenton-like discoloration of Orange II dye using H2O2 as an
      oxidant under visible-light irradiation (lambda>420 nm). It was found the
      CuFe2O4@C3N4 hybrid (mass ratio of CuFe2O4/g-C3N4 at 2:1) exhibits a superior
      activity as compared with single component of CuFe2O4 or g-C3N4 and the mixture
      of g-C3N4 and CuFe2O4, due to the elevation of the separation efficiency of
      photoinduced electron-hole pairs, resulted from the heterojunction between the
      interfaces of g-C3N4 and CuFe2O4. The quenching tests of different scavengers
      displayed that O2(*-), OH and h(+) are responsible for the Orange II
      decolorization. In addition, the effects of initial concentration of the dye
      contaminant (0.014-0.140 mM), different anions (Cl(-), SO4(2-), NO3(-), CH3COO(-)
      and HCO3(-)) and temperature (15-65  degrees C) in photoreaction were also
      investigated. The CuFe2O4@C3N4 sample exhibited stable performance without
      obvious loss of catalytic activity after five successive runs, showing a
      promising application for the photo-oxidative degradation of environmental
      contaminants.

PMID- 25974660
TI  - Carbonaceous composition changes of heavy-duty diesel engine particles in
      relation to biodiesels, aftertreatments and engine loads.
AB  - Three biodiesels and two aftertreatments were tested on a heavy-duty diesel
      engine under the US FTP transient cycle and additional four steady engine loads.
      The objective was to examine their effects on the gaseous and particulate
      emissions, with emphasis given to the organic and elemental carbon (OC and EC) in
      the total particulate matter. Negligible differences were observed between the
      low-sulfur (B1S50) and ultralow-sulfur (B1S10) biodiesels, whereas small
      reductions of OC were identified with the 10% biodiesel blend (B10). The use of
      diesel oxidation catalyst (DOC1) showed moderate reductions of EC and
      particularly OC, resulting in the OC/EC ratio well below unity. The use of DOC
      plus diesel particulate filter (DOC2+DPF) yielded substantial reductions of OC
      and particularly EC, resulting in the OC/EC ratio well above unity. The OC/EC
      ratios were substantially above unity at idle and low load, whereas below unity
      at medium and high load. The above changes in particulate OC and EC are discussed
      with respect to the fuel content, pollutant removal mechanisms and engine
      combustion conditions. Overall, the present study shows that the carbonaceous
      composition of PM could change drastically with engine load and aftertreatments,
      and to a lesser extent with the biodiesels under study. 

PMID- 25974661
TI  - Diagnosis of Helicobacter pylori-induced gastritis by serum pepsinogen levels.
AB  - BACKGROUND AND AIM: Gastric cancer develops due to atrophic gastritis induced by
      Helicobacter pylori (H. pylori) infection. Serum levels of pepsinogen (PG) are
      known to be excellent markers for evaluating the degree of atrophic gastritis. We
      investigated whether chronic gastritis could be diagnosed by evaluating serum PG
      levels. METHODS: A total of 4483 patients (average age, 49.7 years; 2879 men)
      were included in this study. Fasting serum samples were collected and anti-H.
      pylori antibody and PG levels were evaluated. We evaluated the endoscopic atrophy
      grade or histological extent of gastritis, and calculated the diagnostic
      capability of this serum marker. RESULTS: A total of 4483 patients, were
      diagnosed as being positive (4160) or negative (323) for H. pylori-induced
      gastritis. In patients with H. pylori-induced gastritis, the PG II levels were
      higher and the PG I/II ratios were lower than among those without H. pylori
      gastritis. A cut-off values of (i) PG I/II <= 5; (ii) PG II >= 10 or PG I/II <=
      5; (iii) PG II >= 12 or PG I/II <= 4.5 showed high sensitivity and accuracy (over
      90%) for diagnosing H. pylori-induced gastritis. Moreover, in a mass screening of
      healthy subjects, a cut-off value of PG I/II <= 4.5 might be better for
      diagnosing the presence of gastritis because of a sensitivity and specificity >
      80%. CONCLUSIONS: The presence of H. pylori-induced gastritis can be evaluated
      using serum PG levels.

PMID- 25974662
TI  - Pocket Hematoma: A Call for Definition.
AB  - Pocket hematoma is a common complication of cardiac implantable electronic device
      procedures and a potential risk factor for device infections, especially in
      patients on oral anticoagulation or antiplatelet treatment. There is a wide
      variability in the incidence of pocket hematoma and bleeding complications in the
      literature and the major cause for this seems to be the variability of the used
      definitions for hematomas. The lack of generally accepted definition for pocket
      hematoma renders the comparisons across the studies difficult. In this article,
      we briefly review the current literature on this issue and propose a uniform
      definition for pocket hematoma and criteria for grading the severity of hematoma
      in clinical practice and research. 

PMID- 25974663
TI  - ACR Appropriateness Criteria(r) Metastatic Epidural Spinal Cord Compression and
      Recurrent Spinal Metastasis.
AB  - Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency and
      if left untreated, permanent paralysis will ensue. The treatment of MESCC is
      governed by disease, patient, and treatment factors. Patient's preferences and
      goals of care are to be weighed into the treatment plan. Ideally, a patient with
      MESCC is evaluated by an interdisciplinary team promptly to determine the urgency
      of the clinical scenario. Treatment recommendations must take into consideration
      the risk-benefit profiles of surgical intervention and radiotherapy for the
      particular individual's circumstance, including neurologic status, performance
      status, extent of epidural disease, stability of the spine, extra-spinal disease
      status, and life expectancy. In patients with high spinal instability neoplastic
      score (SINS) or retropulsion of bone fragments in the spinal canal, surgical
      intervention should be strongly considered. The rate of development of motor
      deficits from spinal cord compression may be a prognostic factor for ultimate
      functional outcome, and should be taken into account when a treatment
      recommendation is made. The American College of Radiology Appropriateness
      Criteria are evidence-based guidelines for specific clinical conditions that are
      reviewed every three years by a multidisciplinary expert panel. The guideline
      development and review include an extensive analysis of current medical
      literature from peer-reviewed journals and the application of a well-established
      consensus methodology (modified Delphi) to rate the appropriateness of imaging
      and treatment procedures by the panel. In those instances where evidence is
      lacking or not definitive, expert opinion may be used to recommend imaging or
      treatment. 

PMID- 25974664
TI  - Identifying Etiologically Distinct Sub-Types of Cancer: A Demonstration Project
      Involving Breast Cancer.
AB  - With the advent of increasingly detailed molecular portraits of tumor specimens,
      much attention has been directed toward identifying clinically distinct subtypes
      of cancer. Subtyping of tumors can also be accomplished with the goal of
      identifying distinct etiologies. We demonstrate the use of new methodologies to
      identify genes that distinguish etiologically heterogeneous subtypes of breast
      cancer using data from the case-control Cancer and Steroid Hormone Study. Tumor
      specimens were evaluated using a breast cancer expression panel of 196 genes.
      Using a statistical measure that distinguishes the degree of etiologic
      heterogeneity in tumor subtypes, each gene is ranked on the basis of its ability
      to distinguish etiologically distinct subtypes. This is accomplished
      independently using case-control comparisons and by examining the concordance
      odds ratios in double primaries. The estrogen receptor gene, and others in this
      pathway with expression levels that correlated strongly with estrogen receptor
      levels, demonstrate high degrees of etiologic heterogeneity in both methods. Our
      results are consistent with a growing literature that confirms the distinct
      etiologies of breast cancers classified on the basis of estrogen receptor
      expression levels. This proof-of-principle project demonstrates the viability of
      new strategies to identify genomic features that distinguish subtypes of cancer
      from an etiologic perspective.

PMID- 25974665
TI  - The complete chloroplast genome sequence of the evergreen plant Dendropanax
      dentiger (Araliaceae).
AB  - The complete chloroplast genome of the evergreen plant Dendropanax dentiger
      (Araliaceae) has been reconstructed from the whole-genome Illumina sequencing
      data. The circular genome is 156,687 bp in size, and comprises a pair of inverted
      repeat (IR) regions of 25,880 bp each, a large single-copy (LSC) region of 86,680
      bp, and a small single-copy (SSC) region of 18,247 bp. The chloroplast genome
      contains 134 genes, including 89 protein-coding genes (81 PCG species), eight
      ribosomal RNA genes (four rRNA species), and 37 transfer RNA genes (30 tRNA
      species). Out of these genes, 16 harbor a single intron, and two contain a couple
      of introns. The overall A + T content of the whole genome is 62.0%, while the
      corresponding values of the LSC, SSC, and IR regions are 63.8%, 68.0% and 56.9%,
      respectively.

PMID- 25974666
TI  - Illumina next-generation sequencing reveals the complete mitochondrial genome of
      Psenopsis anomala (Perciformes: Centrolophidae) with phylogenetic consideration.
AB  - Using Illumina next-generation sequencing (NGS), the complete mitochondrial
      genome of the Psenopsis anomala was sequenced in the present study. The
      mitochondrial genome of P. anomala is 16,528 bp long and consists of 13 protein
      coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. The structure
      about gene order and composition of P. anomala mitochondrial genome is similar to
      those of most other vertebrates. The nucleotide compositions of the light strand
      in descending order is 29.18% of T, 27.97% of G, 27.06% of A, and 15.79% of C.
      With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA
      genes, other mitochondrial genes are encoded on the heavy strand. The
      phylogenetic analysis by maximum-likelihood (ML) method shown that the Psenopsis
      anomala was closer to Peprilus triacanthus in the phylogenetic relationship.

PMID- 25974667
TI  - Complete mitochondrial genome of the Tyto longimembris (Strigiformes: Tytonidae).
AB  - The complete mitochondrial genome of Tyto longimembris has been determined in
      this study. It is 18,466 bp in length and consists of 13 protein-coding genes, 22
      transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and a non-coding control
      region (D-loop). The overall base composition of the heavy strand of the T.
      longimembris mitochondrial genome is A: 30.1%, T: 23.5%, C: 31.8% and G: 14.6%.
      The structure of control region should be characterized by a region containing
      tandem repeats as two definitely separated clusters of tandem repeats were found.
      This study provided an important data set for phylogenetic and taxonomic analyses
      of Tyto species.

PMID- 25974669
TI  - Synthesis, spectral, computational and thermal analysis studies of
      metallocefotaxime antibiotics.
AB  - Cefotaxime metal complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II),
      Zn(II), Cd(II), Hg(II) and two mixed metals complexes of (Fe,Cu) and (Fe,Ni) were
      synthesized and characterized by elemental analysis, IR, electronic spectra,
      magnetic susceptibility and ESR spectra. The studies proved that cefotaxime may
      act as mono, bi, tri and tetra-dentate ligand through oxygen atoms of lactam
      carbonyl, carboxylic or amide carbonyl groups and nitrogen atom of thiazole ring.
      From the magnetic measurements and electronic spectral data, octahedral
      structures were proposed for all complexes. Quantum chemical methods have been
      performed for cefotaxime to calculate charges, bond lengths, bond angles,
      dihedral angles, electronegativity (chi), chemical potential (MU), global
      hardness (eta), softness (sigma) and the electrophilicity index (omega). The
      thermal decomposition of the prepared metals complexes was studied by TGA, DTA
      and DSC techniques. Thermogravimetric studies revealed the presence of lattice or
      coordinated water molecules in all the prepared complexes. The decomposition
      mechanisms were suggested. The thermal decomposition of the complexes ended with
      the formation of metal oxides and carbon residue as a final product except in
      case of Hg complex, sublimation occur at the temperature range 376.5-575.0 
      degrees C so, only carbon residue was produced during thermal decomposition. The
      orders of chemical reactions (n) were calculated via the peak symmetry method and
      the activation parameters were computed from the thermal decomposition data. The
      geometries of complexes may be converted from Oh to Td during the thermal
      decomposition steps.

PMID- 25974668
TI  - Differential Sox10 genomic occupancy in myelinating glia.
AB  - Myelin is formed by specialized myelinating glia: oligodendrocytes and Schwann
      cells in the central and peripheral nervous systems, respectively. While there
      are distinct developmental aspects and regulatory pathways in these two cell
      types, myelination in both systems requires the transcriptional activator Sox10.
      Sox10 interacts with cell type-specific transcription factors at some loci to
      induce myelin gene expression, but it is largely unknown how Sox10
      transcriptional networks globally compare between oligodendrocytes and Schwann
      cells. We used in vivo ChIP-Seq analysis of spinal cord and peripheral nerve
      (sciatic nerve) to identify unique and shared Sox10 binding sites and assess
      their correlation with active enhancers and transcriptional profiles in
      oligodendrocytes and Schwann cells. Sox10 binding sites overlap with active
      enhancers and critical cell type-specific regulators of myelination, such as
      Olig2 and Myrf in oligodendrocytes, and Egr2/Krox20 in Schwann cells. Sox10 sites
      also associate with genes critical for myelination in both oligodendrocytes and
      Schwann cells and are found within super-enhancers previously defined in brain.
      In Schwann cells, Sox10 sites contain binding motifs of putative partners in the
      Sp/Klf, Tead, and nuclear receptor protein families. Specifically, siRNA analysis
      of nuclear receptors Nr2f1 and Nr2f2 revealed downregulation of myelin genes Mbp
      and Ndrg1 in primary Schwann cells. Our analysis highlights different mechanisms
      that establish cell type-specific genomic occupancy of Sox10, which reflects the
      unique characteristics of oligodendrocyte and Schwann cell differentiation. GLIA
      2015;63:1897-1914.

PMID- 25974670
TI  - Spectrophotometric determination of basic fuchsin from various water samples
      after vortex assisted solid phase extraction using reduced graphene oxide as an
      adsorbent.
AB  - In this study, a fast and simple vortex assisted solid phase extraction method
      was developed for the separation/preconcentration of basic fuchsin in various
      water samples. The determination of basic fuchsin was carried out at a wavelength
      of 554 nm by spectrophotometry. Reduced graphene oxide which was used as a solid
      phase extractor was synthesized and characterized by X-ray diffraction, scanning
      electron microscopy and the Brunauer, Emmett and Teller. The optimum conditions
      are as follows: pH 2, contact times for adsorption and elution of 30 s and 90 s,
      respectively, 10 mg adsorbent, and eluent (ethanol) volume of 1 mL. The effects
      of some interfering ions and dyes were investigated. The method was linear in the
      concentration range of 50-250 MUg L(-1). The adsorption capacity was 34.1 mg g(
      1). The preconcentration factor, limit of detection and precision (RSD, %) of the
      method were found to be 400, 0.07 MUg L(-1) and 1.2%, respectively. The described
      method was validated by analyzing basic fuchsin spiked certified reference
      material (SPS-WW1 Batch 114-Wastewater) and spiked real water samples.

PMID- 25974671
TI  - (2E)-1-(5-Chlorothiophen-2-yl)-3-{4-[(E)-2-phenylethenyl]phenyl}prop-2-en-1-one:
      Synthesis, XRD, FT-IR, Raman and DFT studies.
AB  - A novel (2E)-1-(5-chlorothiophen-2-yl)-3-{4-[(E)-2-phenylethenyl]phenyl}prop-2-en
      1-one [C21H15ClOS] compound has been synthesized and its structure has been
      characterized by FT-IR, Raman and single-crystal X-ray diffraction techniques.
      The conformational isomers, optimized geometric parameters, normal mode
      frequencies and corresponding vibrational assignments of the compound have been
      examined by means of HF, MP2, BP86, BLYP, BMK, B3LYP, B3PW91, B3P86 and M06-2X
      functionals. Reliable vibrational assignments and molecular orbitals have been
      investigated by the potential energy distribution and natural bonding orbital
      analyses, respectively. The compound crystallizes in the triclinic space group P
      1 with the cis-trans-trans form. There is a good agreement between the
      experimentally determined structural parameters and vibrational frequencies of
      the compound and those predicted theoretically using the density functional
      theory with the BLYP and BP86 functionals. 

PMID- 25974672
TI  - Galvanic replacement synthesis of silver dendrites-reduced graphene oxide
      composites and their surface-enhanced Raman scattering characteristics.
AB  - A simple method was developed to synthesize Ag dendrites/reduced graphene oxide
      (AgD/RGO) composites based on the galvanic displacement method. AgNO3 was used as
      the precursor for Ag dendrites and aluminum foils served as the sacrifice metal.
      The as-synthesized AgD/RGO composite was characterized by SEM, FTIR, UV-vis
      spectroscopy and Raman spectroscopy. The results showed that the graphene oxide
      was successfully incorporated into the Ag dendritic structure and was reduced
      during the galvanic displacement between Ag(+) ions and the aluminum foil. XRD
      analysis revealed that the Ag formed in the composite was in the cubic phase. The
      surface-enhanced Raman scattering (SERS) property of the as synthesized AgD/RGO
      composite was evaluated using Rhodamine B as a probe. The composite deposited
      substrate exhibited a much higher SERS activity compared with substrates modified
      with Ag dendrites or GO, indicating that the AgD/RGO could potentially be used as
      a highly sensitive SERS substrate for molecule detecting applications. 

PMID- 25974674
TI  - Vibrational studies (FTIR and Raman), conformational analysis, NBO, HOMO-LUMO and
      reactivity descriptors of S-methyl thiobutanoate, CH3CH2CH2C(O)SCH3.
AB  - In the present article, the molecular structure of S-methyl thiobutanoate,
      CH3CH2CH2C(O)SCH3 was determined by ab initio (MP2) and DFT calculations using
      different basis sets. The infrared and Raman spectra for the liquid phase were
      also recorded and the bands observed were assigned to the vibrational normal
      modes. The experimental and calculations confirm the presence of two most stable
      conformers, one with pseudo anti-syn conformation and another with gauche-syn
      conformation. The study was completed using natural bond orbital (NBO) and AIM
      analysis. The molecular properties like dipole moment, molecular electrostatic
      potential surface (MEP) and HOMO-LUMO molecular orbitals were calculated to get a
      better insight of the properties of the title molecule. Global and local
      reactivity descriptors were computed in order to predict reactivity and reactive
      sites on the molecule for nucleophilic, electrophilic and radical attacks. 

PMID- 25974673
TI  - Quantitative analysis of cyclic dimer fatty acid content in the dimerization
      product by proton NMR spectroscopy.
AB  - In this work, (1)H NMR is utilized for the quantitative analysis of a specific
      cyclic dimer fatty acid in a dimer acid mixture using the pseudo-standard
      material of mesitylene on the basis of its structural similarity. Mesitylene and
      cyclic dimer acid levels were determined using the signal of the proton on the
      cyclic ring (delta=6.8) referenced to the signal of maleic acid (delta=6.2). The
      content of the cyclic dimer fatty acid was successfully determined through the
      standard curve of mesitylene and the reported equation. Using the linearity of
      the mesitylene curve, the cyclic dimer fatty acid in the oil mixture was
      quantified. The results suggest that the proposed method can be used to quantify
      cyclic compounds in mixtures to optimize the dimerization process.

PMID- 25974675
TI  - Identification of copper phthalocyanine blue polymorphs in unaged and aged paint
      systems by means of micro-Raman spectroscopy and Random Forest.
AB  - Copper phthalocyanine (CuPc) blues (PB15) are largely used in art and industry as
      pigments. In these fields mainly three different polymorphic modifications of
      PB15 are employed: alpha, beta and epsilon. Differentiating among these CuPc
      forms can give important information for developing conservation strategy and can
      help in relative dating, since each form was introduced in the market in
      different time periods. This study focuses on the classification of Raman spectra
      measured using 532 nm excitation wavelength on: (i) dry pigment powders, (ii)
      unaged mock-ups of self-made paints, (iii) unaged commercial paints, and (iv)
      paints subjected to accelerated UV ageing. The ratios among integrated Raman
      bands are taken in consideration as features to perform Random Forest (RF).
      Features selection based on Gini Contrast score was carried out on the measured
      dataset to determine the Raman bands ratios with higher predictive power. These
      were used as polymorphic markers, in order to establish an easy and accessible
      method for the identification. Three different ratios and the presence of a
      characteristic vibrational band allowed the identification of the crystal
      modification in pigments powder as well as in unaged and aged paint films.

PMID- 25974676
TI  - Intramolecular aggregation and optical limiting properties of triazine-linked
      mono-, bis- and tris-phthalocyanines.
AB  - A series of triazine-linked mono-, bis- and tris-phthalocyanines are synthesized,
      intramolecular aggregation is found in bis- and tris-phthalocyanines via pi-pi
      stacking interaction. Theoretical and experimental studies reveal the formation
      of the intramolecular aggregation. The spectrographic, photophysical and
      nonlinear optical properties of these compounds are adjusted for the formation of
      the intramolecular aggregation. The bis-phthalocyanine dimer presents smaller
      fluorescence quantum yield, lower triplet formation yield and the triplet-minus
      ground state extinction coefficient, which causes poorer optical limiting
      performance. It is interesting that the tris-phthalocyanine is composed of a mono
      phthalocyanine part and a bis-phthalocyanine part, the optical limiting property
      of the tris-phthalocyanine is similar to that of mono-phthalocyanine. 

PMID- 25974677
TI  - Application of Koopmans' theorem for density functional theory to full valence
      band photoemission spectroscopy modeling.
AB  - In this work, Koopmans' theorem for Kohn-Sham density functional theory (KS-DFT)
      is applied to the photoemission spectra (PES) modeling over the entire valence
      band. To examine the validity of this application, a PES modeling scheme is
      developed to facilitate a full valence-band comparison of theoretical PES spectra
      with experiments. The PES model incorporates the variations of electron
      ionization cross-sections over atomic orbitals and a linear dispersion of
      spectral broadening widths. KS-DFT simulations of pristine rubrene (5,6,11,12
      tetraphenyltetracene) and potassium-rubrene complex are performed, and the
      simulation results are used as the input to the PES models. Two conclusions are
      reached. First, decompositions of the theoretical total spectra show that the
      dissociated electron of the potassium mainly remains on the backbone and has
      little effect on the electronic structures of phenyl side groups. This and other
      electronic-structure results deduced from the spectral decompositions have been
      qualitatively obtained with the anionic approximation to potassium-rubrene
      complexes. The qualitative validity of the anionic approximation is thus
      verified. Second, comparison of the theoretical PES with the experiments shows
      that the full-scale simulations combined with the PES modeling methods greatly
      enhance the agreement on spectral shapes over the anionic approximation. This
      agreement of the theoretical PES spectra with the experiments over the full
      valence-band can be regarded, to some extent, as a collective validation of the
      application of Koopmans' theorem for KS-DFT to valence-band PES, at least, for
      this hydrocarbon and its alkali-adsorbed complex. 

PMID- 25974679
TI  - Infrared Signature of the Cation-pi Interaction between Calcite and Aromatic
      Hydrocarbons.
AB  - The cation-pi interaction is proposed as an important mechanism for the
      adsorption of aromatic hydrocarbons having non-zero quadrupole moments by mineral
      surfaces. Direct evidence supporting such a mechanism is, however, limited. Using
      the model mineral calcite, we probe the cation-pi interaction with adsorbed
      benzene, toluene, and ethylbenzene (BTE) molecules using attenuated total
      reflectance Fourier transform infrared spectroscopy. We show that the presence of
      calcite increases the energy required to excite the synchronized bending of
      aromatic C-H bonds of BTE molecules. The unique conformation of this vibrational
      mode indicates that the planar aromatic rings of BTE molecules are constrained in
      a tilted face-down position by the cation-pi interaction, as further confirmed by
      density functional theory calculations. Our results suggest that the shift of the
      excitation energy of the aromatic C-H bending may be used as an infrared
      signature for the cation-pi interaction occurring on mineral surfaces. 

PMID- 25974678
TI  - Musculoskeletal desmoid tumours: Diagnostic imaging appearances.
AB  - This study aimed to discuss the role medical imaging has on diagnosis of
      musculoskeletal desmoid tumours and to describe their radiological appearances on
      various imaging modalities. Imaging of histologically proven cases of desmoid
      tumours at St. Vincent's Hospital Melbourne were obtained via picture archiving
      communication system (PACS) and then assessed by two musculoskeletal
      radiologists. Suitable imagings were obtained from PACS. All imaging chosen was
      de-identified. Desmoid tumours can occur in many areas of the body. Imaging plays
      an important role in the diagnosis of these tumours and magnetic resonance
      imaging has been the gold standard for imaging and is the most accurate in terms
      of assessing tumour margins and involvement of surrounding structures. 

PMID- 25974683
TI  - Letter to the Editor: Computer Vision Syndrome and Blink Rate.

PMID- 25974682
TI  - Whole-body vibration and blood flow and muscle oxygenation: a meta-analysis.
AB  - CONTEXT: The use and popularity of whole-body vibration (WBV) has increased in
      recent years, but there is a lack of consensus in the literature about the
      effectiveness of the treatment. OBJECTIVE: To quantitatively examine the effects
      of WBV on muscle oxygenation and peripheral blood flow in healthy adults. DATA
      SOURCES: We searched Web of Science and PubMed databases and reference lists from
      relevant articles using the key terms whole body vibration, whole-body vibration,
      WBV, blood flow, peripheral blood flow, oxygenation, muscle oxygenation,
      circulation, circulatory, near infrared spectroscopy, NIRS, and power Doppler.
      Key terms were searched using single word and combination searches. No date range
      was specified. STUDY SELECTION: Criteria for inclusion were (1) use of a
      commercially available WBV device, (2) a human research model, (3) a pre-WBV
      condition and at least 1 WBV experimental condition, and (4) reporting of
      unstandardized means and standard deviations of muscle oxygenation or peripheral
      blood flow. DATA EXTRACTION: Means, standard deviations, and sample sizes were
      extracted from the text, tables, and figures of included studies. A total of 35
      and 90 data points were extracted for the muscle-oxygenation and blood-flow meta
      analyses, respectively. Data for each meta-analysis were combined and analyzed
      using meta-analysis software. Weighted, random-effects meta-analyses using the
      Hedges g metric were completed for muscle oxygenation and blood flow. We then
      conducted follow-up analyses using the moderator variables of vibration type,
      vibration time, vibration frequency, measurement location, and sample type. DATA
      SYNTHESIS: We found 18 potential articles. Further examination yielded 10 studies
      meeting the inclusion criteria. Whole-body vibration was shown to positively
      influence peripheral blood flow. Additionally, the moderators of vibration type
      and frequency altered the influence of WBV on blood flow. Overall, WBV did not
      alter muscle oxygenation; however, when the measurement site was considered,
      muscle oxygenation increased or decreased depending on the location. CONCLUSIONS:
      Acute bouts of WBV increase peripheral blood flow but do not alter skeletal
      muscle oxygenation. Vibration type appears to be the most important factor
      influencing both muscle oxygenation and peripheral blood flow.

PMID- 25974684
TI  - The Effect of Incentives and Meta-incentives on the Evolution of Cooperation.
AB  - Although positive incentives for cooperators and/or negative incentives for free
      riders in social dilemmas play an important role in maintaining cooperation,
      there is still the outstanding issue of who should pay the cost of incentives.
      The second-order free-rider problem, in which players who do not provide the
      incentives dominate in a game, is a well-known academic challenge. In order to
      meet this challenge, we devise and analyze a meta-incentive game that integrates
      positive incentives (rewards) and negative incentives (punishments) with second
      order incentives, which are incentives for other players' incentives. The
      critical assumption of our model is that players who tend to provide incentives
      to other players for their cooperative or non-cooperative behavior also tend to
      provide incentives to their incentive behaviors. In this paper, we solve the
      replicator dynamics for a simple version of the game and analytically categorize
      the game types into four groups. We find that the second-order free-rider problem
      is completely resolved without any third-order or higher (meta) incentive under
      the assumption. To do so, a second-order costly incentive, which is given
      individually (peer-to-peer) after playing donation games, is needed. The paper
      concludes that (1) second-order incentives for first-order reward are necessary
      for cooperative regimes, (2) a system without first-order rewards cannot maintain
      a cooperative regime, (3) a system with first-order rewards and no incentives for
      rewards is the worst because it never reaches cooperation, and (4) a system with
      rewards for incentives is more likely to be a cooperative regime than a system
      with punishments for incentives when the cost-effect ratio of incentives is
      sufficiently large. This solution is general and strong in the sense that the
      game does not need any centralized institution or proactive system for
      incentives. 

PMID- 25974685
TI  - Skeletal plasticity in response to embryonic muscular activity underlies the
      development and evolution of the perching digit of birds.
AB  - Most birds have an opposable digit 1 (hallux) allowing the foot to grasp, which
      evolved from the non-opposable hallux of early theropod dinosaurs. An important
      morphological difference with early theropods is the twisting of the long axis of
      its metatarsal. Here, we show how embryonic musculature and the onset of its
      activity are required for twisting of metatarsal 1 (Mt1) and retroversion of the
      hallux. Pharmacologically paralyzed embryos do not fully retrovert the hallux and
      have a straight Mt1 shaft, phenocopying the morphology of early tetanuran
      dinosaurs. Molecular markers of cartilage maturation and ossification show that
      differentiation of Mt1 is significantly delayed compared to Mt2-4. We hypothesize
      on how delayed maturation may have increased plasticity, facilitating muscular
      twisting. Our experimental results emphasize the importance of embryonic muscular
      activity in the evolutionary origin of a crucial adaptation. 

PMID- 25974686
TI  - Cullin 3 Recognition Is Not a Universal Property among KCTD Proteins.
AB  - Cullin 3 (Cul3) recognition by BTB domains is a key process in protein
      ubiquitination. Among Cul3 binders, a great attention is currently devoted to
      KCTD proteins, which are implicated in fundamental biological processes. On the
      basis of the high similarity of BTB domains of these proteins, it has been
      suggested that the ability to bind Cul3 could be a general property among all
      KCTDs. In order to gain new insights into KCTD functionality, we here evaluated
      and/or quantified the binding of Cul3 to the BTB of KCTD proteins, which are
      known to be involved either in cullin-independent (KCTD12 and KCTD15) or in
      cullin-mediated (KCTD6 and KCTD11) activities. Our data indicate that KCTD6(BTB)
      and KCTD11(BTB) bind Cul3 with high affinity forming stable complexes with 4:4
      stoichiometries. Conversely, KCTD12(BTB) and KCTD15(BTB) do not interact with
      Cul3, despite the high level of sequence identity with the BTB domains of cullin
      binding KCTDs. Intriguingly, comparative sequence analyses indicate that the
      capability of KCTD proteins to recognize Cul3 has been lost more than once in
      distinct events along the evolution. Present findings also provide interesting
      clues on the structural determinants of Cul3-KCTD recognition. Indeed, the
      characterization of a chimeric variant of KCTD11 demonstrates that the swapping
      of alpha2beta3 loop between KCTD11(BTB) and KCTD12(BTB) is sufficient to abolish
      the ability of KCTD11(BTB) to bind Cul3. Finally, present findings, along with
      previous literature data, provide a virtually complete coverage of Cul3 binding
      ability of the members of the entire KCTD family.

PMID- 25974687
TI  - Cytogenetic heterogeneity and their serial dynamic changes during acquisition of
      cytogenetic aberrations in cultured mesenchymal stem cells.
AB  - To minimize the risk of tumorigenesis in mesenchymal stem cells (MSCs), G-banding
      analysis is widely used to detect chromosomal aberrations in MSCs. However, a
      critical limitation of G-banding is that it only reflects the status of metaphase
      cells, which can represent as few as 0.01% of tested cells. During routine
      cytogenetic testing in MSCs, we often detect chromosomal aberrations in minor
      cell populations. Therefore, we aimed to investigate whether such a minority of
      cells can expand over time or if they ultimately disappear during MSC passaging.
      We passaged MSCs serially while monitoring quantitative changes for each aberrant
      clone among heterogeneous MSCs. To investigate the cytogenetic status of
      interphase cells, which represent the main population, we also performed
      interphase FISH analysis, in combination with G-banding and telomere length
      determination. In human adipose tissue-derived MSCs, 4 types of chromosomal
      aberrations were found during culturing, and in umbilical cord MSCs, 2 types of
      chromosomal aberrations were observed. Sequential dynamic changes among
      heterogeneous aberrant clones during passaging were similar to the dynamic
      changes observed in cancer stem cells during disease progression. Throughout all
      passages, the quantitative G-banding results were inconsistent with those of the
      interphase FISH analysis. Interphase FISH revealed hidden aberrations in stem
      cell populations with normal karyotypes by G-banding analysis. We found that
      telomere length gradually decreased during passaging until the point at which
      cytogenetic aberrations appeared. The present study demonstrates that rare
      aberrant clones at earlier passages can become predominant clones during later
      passages. Considering the risk of tumorigenesis due to aberrant MSCs, we believe
      that our results will help to establish proper safety guidelines for MSC use. In
      particular, we believe it is critical to test for chromosomal aberrations using
      both G-banding and FISH to ensure the safety of human stem cells that are
      manufactured in vitro for clinical applications. 

PMID- 25974688
TI  - Chirality Transfer and Modulation in LB Films Derived From the
      Diacetylene/Melamine Hydrogen-Bonded Complex.
AB  - Introduction of hydrogen-bonding interaction into pi-conjugated systems is a
      promising strategy, since the highly selective and directional hydrogen-bonding
      can increase the binding strength, provide enhanced stability to the assemblies,
      and position the pi-conjugated molecules in a desired arrangement. The helical
      packing of the rigid melamine cores seems to play a dominating role in the
      subsequent formation of the peripheral helical PDA backbone. The polymerized
      Langmuir-Blodgett (LB) films exhibited reversible colorimetric and chiroptical
      changes during repeated heating-cooling cycles, which should be ascribed to the
      strong hydrogen-bonding interaction between the carboxylic acid and the melamine
      core. Further, the closely helical packing of the melamine cores could be
      destroyed upon exposure to HCl or NH(3) gas, whereas the peripheral helical
      polyaniline and polydiacetylene (PDA) backbone exhibited excellent stability.
      Although similar absorption changes could be observed for the films upon exposure
      to HCl or NH(3) gas, their distinct circular dichroism (CD) responses enabled us
      to distinguish the above two stimuli.

PMID- 25974689
TI  - Agonal Thrombi at Autopsy.
AB  - Clots and thrombi identified at autopsy are generally classified dichotomously as
      antemortem or postmortem. Current articles and textbooks support this approach.
      Earlier literature often contained descriptions of a third category, the agonal
      thrombus that forms while the patient is dying. We collected 238 autopsy cases
      including 80 rapid/sudden deaths by violence and 21 (including 1 pediatric)
      deaths from acute pulmonary emboli. We analyzed the gross and microscopic
      features of clots and thrombi. Agonal thrombi were identified in 122 cases (89%
      of cases of "slow" death). Agonal thrombi were not identified in cases of sudden
      death. We found that a comprehensive description of the macroscopic features was
      a key to interpretation. The gross and microscopic features of agonal thrombi
      "chicken fat" support their hybrid nature. The dichotomous classification of
      clots and thrombi seems to be founded on assumptions of clinical significance but
      is perhaps oversimplified. Agonal thrombi area distinct class of thrombus that,
      although not clinically significant as an immediate cause of death, arises by its
      own mechanisms and has its own morphology. It is advisable to avoid classifying
      agonal thrombi as mere postmortem clots because in forensic cases, they may help
      support an argument against sudden death. 

PMID- 25974690
TI  - Structural Integrity of the A147T Polymorph of Mammalian TSPO.
AB  - Ligands of the transmembrane protein TSPO are used for imaging of brain
      inflammation, but a common polymorphism in TSPO complicates their application to
      humans. Here we determined the three-dimensional structure and side-chain
      dynamics of the A147T polymorph of mammalian TSPO in complex with the first
      generation ligand PK11195. We show that A147T TSPO is able to retain the same
      structural and dynamic profile as the wild-type protein and thus binds PK11195
      with comparable affinity. Our study is important for the design of more potent
      diagnostic and therapeutic ligands of TSPO. 

PMID- 25974691
TI  - Correction of Adult Scimitar Syndrome Using a Lateral Endoscopic Approach with
      Robotics.
AB  - We present two adult patients in whom anatomic correction of scimitar syndrome
      (SS) was accomplished by redirecting the anomalous pulmonary venous drainage into
      the left atrium using a reinforced polytetrafluoroethylene (PTFE) graft
      extension. A right lateral endoscopic approach with robotic instrumentation
      (LEAR) was utilized with excellent early and long-term results.

PMID- 25974693
TI  - New Insights into the Regulation of Chylomicron Production.
AB  - Dietary lipids are efficiently absorbed by the small intestine, incorporated into
      triglyceride-rich lipoproteins (chylomicrons), and transported in the circulation
      to various tissues. Intestinal lipid absorption and mobilization and chylomicron
      synthesis and secretion are highly regulated processes. Elevated chylomicron
      production rate contributes to the dyslipidemia seen in common metabolic
      disorders such as insulin-resistant states and type 2 diabetes and likely
      increases the risk for atherosclerosis seen in these conditions. An in-depth
      understanding of the regulation of chylomicron production may provide leads for
      the development of drugs that could be of therapeutic utility in the prevention
      of dyslipidemia and atherosclerosis. Chylomicron secretion is subject to
      regulation by various factors, including diet, body weight, genetic variants,
      hormones, nutraceuticals, medications, and emerging interventions such as
      bariatric surgical procedures. In this review we discuss the regulation of
      chylomicron production, mechanisms that underlie chylomicron dysregulation, and
      potential avenues for future research. 

PMID- 25974694
TI  - Regulation of Selenium Metabolism and Transport.
AB  - Selenium is regulated in the body to maintain vital selenoproteins and to avoid
      toxicity. When selenium is limiting, cells utilize it to synthesize the
      selenoproteins most important to them, creating a selenoprotein hierarchy in the
      cell. The liver is the central organ for selenium regulation and produces
      excretory selenium forms to regulate whole-body selenium. It responds to selenium
      deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the
      plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is
      distributed to tissues in relation to their expression of the Sepp1 receptor
      apolipoprotein E receptor-2, creating a tissue selenium hierarchy. N-terminal
      Sepp1 forms are taken up in the renal proximal tubule by another receptor,
      megalin. Thus, the regulated whole-body pool of selenium is shifted to needy
      cells and then to vital selenoproteins in them to supply selenium where it is
      needed, creating a whole-body selenoprotein hierarchy. 

PMID- 25974695
TI  - CoQ10 Function and Role in Heart Failure and Ischemic Heart Disease.
AB  - Coenzyme Q (CoQ) is an essential lipid of cells present in all cellular
      compartments. The functions of CoQ in mitochondrial respiration and as an
      antioxidant are established, although the lipid likely has additional, presently
      unknown, roles. While the therapeutic utility of CoQ10 supplements is recognized
      in the rare cases of primary CoQ10 deficiencies, a potential role for CoQ10
      supplements in cardiovascular disease, particularly heart failure, has also been
      studied for over 40 years. This review summarizes our current knowledge in these
      areas derived from animal studies and human trials. Current evidence for a
      benefit of CoQ10 supplements in diseases other than primary CoQ10 deficiencies is
      insufficient. 

PMID- 25974696
TI  - Mediterranean Dietary Patterns and Cardiovascular Health.
AB  - The Mediterranean dietary pattern has been linked with reduced cardiovascular
      disease incidence and mortality. Components of the Mediterranean diet associated
      with better cardiovascular health include low consumption of meat and meat
      products, moderate consumption of ethanol (mostly from wine), and high
      consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. Increasing
      evidence indicates that the synergy among these components results in beneficial
      changes in intermediate pathways of cardiometabolic risk, such as lipids, insulin
      sensitivity, oxidative stress, inflammation, and vasoreactivity. As a result,
      consumption of a Mediterranean dietary pattern favorably affects numerous
      cardiovascular disease risk factors, such as dyslipidemia, hypertension,
      metabolic syndrome, and diabetes. Moreover, strong evidence links this dietary
      pattern with reduced cardiovascular disease incidence, reoccurrence, and
      mortality. This review evaluates the current evidence behind the cardioprotective
      effects of a Mediterranean dietary pattern. 

PMID- 25974697
TI  - Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian
      Antimicrobial Metabolite.
AB  - Itaconic acid is well known as a precursor for polymer synthesis and has been
      involved in industrial processes for decades. In a recent surprising discovery,
      itaconic acid was found to play a role as an immune-supportive metabolite in
      mammalian immune cells, where it is synthesized as an antimicrobial compound from
      the citric acid cycle intermediate cis-aconitic acid. Although the immune
      responsive gene 1 protein (IRG1) has been associated to immune response without a
      mechanistic function, the critical link to itaconic acid production through an
      enzymatic function of this protein was only recently revealed. In this review, we
      highlight the history of itaconic acid as an industrial and antimicrobial
      compound, starting with its biotechnological synthesis and ending with its
      antimicrobial function in mammalian immune cells. 

PMID- 25974692
TI  - Direct and Functional Biomarkers of Vitamin B6 Status.
AB  - Measures of B6 status are categorized as direct biomarkers and as functional
      biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and
      erythrocytes, and among these plasma pyridoxal 5'-phosphate (PLP) is most
      commonly used. Functional biomarkers include erythrocyte transaminase activities
      and, more recently, plasma levels of metabolites involved in PLP-dependent
      reactions, such as the kynurenine pathway, one-carbon metabolism,
      transsulfuration (cystathionine), and glycine decarboxylation (serine and
      glycine). Vitamin B6 status is best assessed by using a combination of biomarkers
      because of the influence of potential confounders, such as inflammation, alkaline
      phosphatase activity, low serum albumin, renal function, and inorganic phosphate.
      Ratios between substrate-products pairs have recently been investigated as a
      strategy to attenuate such influence. These efforts have provided promising new
      markers such as the PAr index, the 3-hydroxykynurenine:xanthurenic acid ratio,
      and the oxoglutarate:glutamate ratio. Targeted metabolic profiling or untargeted
      metabolomics based on mass spectrometry allow the simultaneous quantification of
      a large number of metabolites, which are currently evaluated as functional
      biomarkers, using data reduction statistics. 

PMID- 25974698
TI  - Manganese Is Essential for Neuronal Health.
AB  - The understanding of manganese (Mn) biology, in particular its cellular
      regulation and role in neurological disease, is an area of expanding interest. Mn
      is an essential micronutrient that is required for the activity of a diverse set
      of enzymatic proteins (e.g., arginase and glutamine synthase). Although necessary
      for life, Mn is toxic in excess. Thus, maintaining appropriate levels of
      intracellular Mn is critical. Unlike other essential metals, cell-level
      homeostatic mechanisms of Mn have not been identified. In this review, we discuss
      common forms of Mn exposure, absorption, and transport via regulated
      uptake/exchange at the gut and blood-brain barrier and via biliary excretion. We
      present the current understanding of cellular uptake and efflux as well as
      subcellular storage and transport of Mn. In addition, we highlight the Mn
      dependent and Mn-responsive pathways implicated in the growing evidence of its
      role in Parkinson's disease and Huntington's disease. We conclude with
      suggestions for future focuses of Mn health-related research. 

PMID- 25974699
TI  - Health Benefits of Long-Term Weight-Loss Maintenance.
AB  - Obesity is a chronic and complex medical condition associated with a large number
      of complications affecting most organs and systems through multiple pathways.
      Strategies for weight management include behavioral, pharmacological, and
      surgical interventions, all of which can result in a reduction in obesity-related
      comorbidities and improvements in quality of life. However, subsequent weight
      regain often reduces the durability of these improvements. The objective of this
      article is to review evidence supporting the long-term effects of intentional
      weight loss on morbidity, mortality, quality of life, and health-care cost.
      Overall, considerable evidence suggests that intentional weight loss is
      associated with clinically relevant benefits for the majority of obesity-related
      comorbidities. However, the degree of weight loss that must be achieved and
      sustained to reap these benefits varies widely between comorbidities. 

PMID- 25974700
TI  - Regulation of the Epigenome by Vitamin C.
AB  - Emerging evidence suggests that ascorbate, the dominant form of vitamin C under
      physiological pH conditions, influences activity of the genome via regulating
      epigenomic processes. Ascorbate serves as a cofactor for Ten-eleven translocation
      (TET) dioxygenases that catalyze the oxidation of 5-methylcytosine (5mC) into 5
      hydroxymethylcytosine (5hmC), and further to 5-formylcytosine (5fC) and to 5
      carboxylcytosine (5caC), which are ultimately replaced by unmodified cytosine.
      The Jumonji C (JmjC)-domain-containing histone demethylases also require
      ascorbate as a cofactor for histone demethylation. Thus, by primarily
      participating in the demethylation of both DNA and histones, ascorbate appears to
      be a mediator of the interface between the genome and environment. Furthermore,
      redox status has a profound impact on the bioavailability of ascorbate in the
      nucleus. In order to bridge the gap between redox biology and genomics, we
      suggest an interdisciplinary research field that can be termed redox genomics to
      study dynamic redox processes in health and diseases. This review examines the
      evidence and potential molecular mechanism of ascorbate in the demethylation of
      the genome, and it highlights potential epigenetic roles of ascorbate in various
      diseases. 

PMID- 25974701
TI  - Glycemic Variability: Assessing Glycemia Differently and the Implications for
      Dietary Management of Diabetes.
AB  - The primary therapeutic target for diabetes management is the achievement of good
      glycemic control, of which glycated hemoglobin (HbA1c) remains the standard
      clinical marker. However, glycemic variability (GV; the amplitude, frequency, and
      duration of glycemic fluctuations around mean blood glucose) is an emerging
      target for blood glucose control. A growing body of evidence supports GV as an
      independent risk factor for diabetes complications. Several techniques have been
      developed to assess and quantify intraday and interday GV. Additionally, GV can
      be influenced by several nutritional factors, including carbohydrate quality,
      quantity; and distribution; protein intake; and fiber intake. These factors have
      important implications for clinical nutrition practice and for optimizing blood
      glucose control for diabetes management. This review discusses the available
      evidence for GV as a marker of glycemic control and risk factor for diabetes
      complications. GV quantification techniques and the influence of nutritional
      considerations for diabetes management are also discussed. 

PMID- 25974704
TI  - Development of the quantitative indicator of abdominal examination for clinical
      application: a pilot study.
AB  - OBJECTIVES: Abdominal examination (AE) is the evaluation of the status of illness
      by examining the abdominal region in traditional Korean medicine (TKM). Although
      AE is currently considered an important diagnostic method in TKM, owing to its
      clinical usage, no studies have been conducted to objectively assess its accuracy
      and develop standards. DESIGN: Twelve healthy subjects and 21 patients with
      functional dyspepsia have participated in this study. The patients were
      classified into epigastric discomfort group (n=11) and epigastric discomfort with
      tenderness group (n=10) according to the clinical diagnosis by AE. After
      evaluating the subjective epigastric discomfort in all subjects, two independent
      clinicians measured the pressure pain threshold (PPT) two times at an acupoint
      (CV 14) using an algometer. We then assessed the interrater and intrarater
      reliability of the PPT measurements and evaluated the validity (sensitivity and
      specificity) via a receiver operating characteristic plot and optimal cutoff
      value. RESULTS: The results of the interrater reliability test showed a very
      strong correlation (correlation coefficient range: 0.82-0.91). The results of
      intrarater reliability test also showed a higher than average correlation
      (intraclass correlation coefficient: 0.58-0.70). The optimal cutoff value of PPT
      in the epigastric area was 1.8 kg/cm(2) with 100% sensitivity and 54.54%
      specificity. CONCLUSIONS: PPT measurements in the epigastric area with an
      algometer demonstrated high reliability and validity for AE, which makes this
      approach potentially useful in clinical applications as a new quantitative
      measurement in TKM.

PMID- 25974703
TI  - Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6
      and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for
      major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can
      influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We
      summarize evidence from the published literature supporting these associations
      and provide dosing recommendations for fluvoxamine, paroxetine, citalopram,
      escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at
      www.pharmgkb.org). 

PMID- 25974705
TI  - Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With
      Special Reference to Astrocytic Tau Pathology.
AB  - Progressive supranuclear palsy (PSP) is a four-repeat tauopathy with tau
      positive, argyrophilic tuft-shaped astrocytes (TAs). We performed a pathological
      and clinical investigation in 40 consecutive autopsied Japanese patients with
      pathological diagnoses of PSP or PSP-like disease. Unequivocal TAs were present
      in 22 cases, all of which were confirmed to be PSP. Such TAs were hardly detected
      in the other 18 cases, which instead exhibited tau-positive, argyrophilic
      astrocytes, appearing as comparatively small clusters with central nuclei of
      irregularly shaped, coarse structures (equivocal TAs). Cluster analysis of the
      distribution pattern of tau-related pathology for these 18 cases identified two
      subgroups, pallido-nigro-luysian atrophy (PNLA) Type 1 (n = 9) and Type 2 (n =
      9), the former being distinguished from the latter by the presence of tau-related
      lesions in the motor cortex, pontine nucleus and cerebellar dentate nucleus in
      addition to the severely affected PNL system. The duration from symptom onset
      until becoming wheelchair-bound was significantly longer in PNLA Type 1.
      Immunoblotting of samples from the three disease conditions revealed band
      patterns of low-molecular-mass tau fragments at ~35 kDa. These findings shed
      further light on the wide pathological and clinical spectrum of four-repeat
      tauopathy, representing PSP in the broad sense rather than classical PSP.

PMID- 25974706
TI  - Erbium(III) Coordination at the Surface of an Aqueous Electrolyte.
AB  - Grazing-incidence (GI) X-ray absorption spectroscopy (XAS) under conditions of
      total external reflection is used to explore the coordination environment of the
      trivalent erbium ion, Er(3+), at an electrolyte-vapor interface. A parallel study
      of the bulk aqueous electrolyte (1 M ErCl3 in HCl at pH = 1.54) shows that the
      Er(3+) ions have a simple hydration shell with an average Er-OH2 bond distance of
      2.33(1) A, consistent with previous descriptions of the aquated cation,
      [Er(OH2)8](3+). No other correlations are observed in the electrolyte EXAFS
      (extended X-ray absorption fine structure) data acquired at room temperature. In
      contrast, the coordination of the Er(3+) ions at the electrolyte-helium
      interface, as interrogated by use of electron-yield detection, reveal
      correlations beyond the Er-OH2 hydration shell that are unexpectedly well
      defined. Analyses show an environment that consists of a first coordination
      sphere of 6-7 O atoms at 2.36(1) A and a second one of 3 Cl atoms at 2.89(2) A,
      suggesting the formation of a neutral [(H2O)6-7ErCl3] entity at the surface of
      the electrolyte. The presence of a third, distant peak in the Fourier transform
      data is attributed to Er-Er correlations (in possible combination with
      contributions from distant Er-O and Er-Cl interactions). The best-Z and -integer
      fits reveal 3 Er atoms at 3.20(2) A, confirming the near-surface-enrichment of
      Er(3+) as revealed previously by use of X-ray reflectivity measurements (J. Phys.
      Chem. C 2013, 117, 19082). Here, the strong associations between the Er-aqua
      chloro entities at the electrolyte-vapor interface are shown to be consistent
      with the formation of domains of polynuclear cluster motifs, such as would arise
      through hydrolysis reactions of the aquated Er(3+) cations. The local structural
      results and the calculated surface coverage are of relevance to understand the
      myriad reactions involved in the hydrometallurgical process of solvent extraction
      (SX) for metal purification, which involves the transfer of a selected metal ion,
      like Er, across an interface from an aqueous electrolyte to an organic phase. 

PMID- 25974702
TI  - Use of Urine Biomarkers to Assess Sodium Intake: Challenges and Opportunities.
AB  - This article summarizes current data and approaches to assess sodium intake in
      individuals and populations. A review of the literature on sodium excretion and
      intake estimation supports the continued use of 24-h urine collections for
      assessing population and individual sodium intake. Since 2000, 29 studies used
      urine biomarkers to estimate population sodium intake, primarily among adults.
      More than half used 24-h urine; the rest used a spot/casual, overnight, or 12-h
      specimen. Associations between individual sodium intake and health outcomes were
      investigated in 13 prospective cohort studies published since 2000. Only three
      included an indicator of long-term individual sodium intake, i.e., multiple 24-h
      urine specimens collected several days apart. Although not insurmountable,
      logistic challenges of 24-h urine collection remain a barrier for research on the
      relationship of sodium intake and chronic disease. Newer approaches, including
      modeling based on shorter collections, offer promise for estimating population
      sodium intake in some groups. 

PMID- 25974707
TI  - Considering the Ectopic Pituitary Gland in Evaluation of the Nasopharyngeal Mass.
AB  - IMPORTANCE: Extracranial pituitary ectopia is an uncommon finding characterized
      by all or a portion of the pituitary gland situated in an aberrant location.
      Often these lesions come to clinical attention only once they begin to function
      abnormally or increase in size significantly. OBSERVATIONS: We describe an
      incidentally noted, asymptomatic pedunculated nasopharyngeal lesion in a 13-month
      old girl that may be an extracranial pituitary gland. Consideration of this rare
      anomaly cautioned against performing a biopsy and may have prevented inadvertent
      removal of functional pituitary tissue. We describe the embryologic origins of
      ectopic pituitary tissue, discuss the differential diagnosis for nasopharyngeal
      lesions in children, and emphasize physical and radiologic findings suggestive of
      ectopic pituitary tissue to prevent potential inadvertent removal of this rare
      anomaly. CONCLUSIONS AND RELEVANCE: We report this unusual case to review
      embryologic origins of ectopic pituitary tissue and to alert otolaryngologists of
      the need to consider ectopic pituitary tissue in the diagnosis of nasopharyngeal
      lesions in children.

PMID- 25974709
TI  - The European Association of Young Neurologists and Trainees in 2015:
      strengthening collaboration with the European Academy of Neurology.

PMID- 25974708
TI  - Identification of a novel class of covalent modifiers of hemoglobin as potential
      antisickling agents.
AB  - Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization
      properties that are beneficial for sickle cell disease therapy. Based on the ECA
      pharmacophore and its atomic interaction with hemoglobin, we designed and
      synthesized several compounds - designated as KAUS (imidazolylacryloyl
      derivatives) - that we hypothesized would bind covalently to betaCys93 of
      hemoglobin and inhibit sickling. The compounds surprisingly showed weak
      allosteric and antisickling properties. X-ray studies of hemoglobin in complex
      with representative KAUS compounds revealed an unanticipated mode of Michael
      addition between the beta-unsaturated carbon and the N-terminal alphaVal1
      nitrogen at the alpha-cleft of hemoglobin, with no observable interaction with
      betaCys93. Interestingly, the compounds exhibited almost no reactivity with the
      free amino acids, L-Val, L-His and L-Lys, but showed some reactivity with both
      glutathione and L-Cys. Our findings provide a molecular level explanation for the
      compounds biological activities and an important framework for targeted
      modifications that would yield novel potent antisickling agents.

PMID- 25974710
TI  - Evaluation of an ICD-10 algorithm to detect osteonecrosis of the jaw among cancer
      patients in the Danish National Registry of Patients.
AB  - PURPOSE: This study aimed to validate a predefined algorithm for osteonecrosis of
      the jaw (ONJ) among cancer patients in the Danish National Registry of Patients
      and to assess the nature of clinical information recorded in medical charts of
      ONJ patients. METHODS: We identified potential ONJ cases recorded in 2005-2010
      among cancer patients at the hospital Departments of Oral and Maxillofacial
      Surgery (DOMS) in three Danish regions, using a set of codes from the
      International Classification of Diseases, 10th revision (ICD-10). We abstracted
      DOMS charts of the potential cases, had the ONJ status adjudicated by an expert
      ONJ adjudication committee (ONJAC), and computed positive predictive values. For
      patients with ONJAC-confirmed ONJ, we abstracted the charts for information on
      ONJ clinical course. Sensitivity of the algorithm was computed using a separate
      sample of 101 known ONJ cases accrued in 2005-2011. RESULTS: We identified 212
      potential ONJ cases, of which 197 (93%) had charts available for abstraction.
      Eighty-three potential cases were confirmed by ONJAC, with a positive predictive
      value of 42% (95% confidence interval [CI] 35%-49%). DOMS charts of these 83
      cases contained complete information on ONJ clinical course. Information about
      antiresorptive treatment was recorded for 84% of the patients. Among the 101
      known ONJ cases, 74 had at least one prespecified ICD-10 code recorded in the
      Danish National Registry of Patients within +/-90 days of the ONJ diagnosis
      (sensitivity 73%; 95%CI [64%-81%]). CONCLUSIONS: The predefined algorithm is not
      adequate for monitoring ONJ in pharmacovigilance studies. Additional case-finding
      approaches, coupled with adjudication, are necessary to estimate ONJ incidence
      accurately.

PMID- 25974711
TI  - Facile Electrospinning of CeO2 /Bi2 WO6 Heterostructured Nanofibers with
      Excellent Visible-light-driven Photocatalytic Performance.
AB  - One-dimensional (1D) CeO2 /Bi2 WO6 heterostructured nanofibers with a diameter of
      about 300 nm were successfully synthesized by using a straightforward strategy
      combining an electrospinning technique with a sintering process. The acquired
      products were characterized by thermogravimetric and differential scanning
      calorimetric (TG-DSC), Fourier transform infrared (FT-IR) spectroscopy, scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller
      (BET) surface area measurements, and UV/Vis spectroscopy. The obtained CeO2 /Bi2
      WO6 heterostructured nanofibers exhibited an excellent photocatalytic property
      for the degradation of Rhodamine B (RhB) dye driven by visible light due to the
      promoted separation of photoelectrons and holes and the large contact area
      between the photocatalyst and organic pollutant. 

PMID- 25974712
TI  - Preparation of 1-Substituted Tetrahydro-beta-carbolines by Lithiation
      Substitution.
AB  - A method to prepare 1-substituted N-Boc-tetrahydro-beta-carbolines was developed
      by lithiation followed by electrophilic substitution. The deprotonation to give
      the organolithium was optimized by in situ IR spectroscopy and showed that the
      Boc group rotates slowly at low temperature. The chemistry was applied to the
      synthesis of 9-methyleleagnine (N-methyltetrahydroharman) and 11-methylharmicine.

PMID- 25974713
TI  - Three new luminescent Cd(II)-MOFs by regulating the tetracarboxylate and
      auxiliary co-ligands, displaying high sensitivity for Fe(3+) in aqueous solution.
AB  - Three new Cd(ii)-MOFs, [Cd(L1)0.5(bpp)] (), [Cd(L1)0.5(bipy)] (), and
      [Cd(L2)0.5(bipy)] () [H4Ln = (1,1':4',1''-terphenyl)-2',x,x'',5'-tetracarboxylic
      acid (n = 1, x = 3, and n = 2, x = 4), bpp = 1,3-di(4-pyridyl)propane, and bipy =
      2,2'-bipyridine], have been synthesized using Cd(ii) ions and isomeric H4Ln
      ligands in the presence of auxiliary ligands via solvothermal reaction, and have
      been fully characterized by elemental analysis, FT-IR spectroscopy, powder X-ray
      diffraction (PXRD), and thermogravimetric analysis (TGA). Complex is a three
      dimensional (3D) pillar-layered network built from L1(4-) and bridging bpp co
      ligands with a binodal (4,8)-connected gsp2 topology and a symbol of
      (4(4).6(2))(4(16).6(12)). was successfully synthesized using bipy instead of the
      bpp ligand used to assemble giving a 2D 4-connected sql net. is a 3D reticular
      framework with [Cd2(COO)4] SBUs based on L2(4-) ligands, displaying a (4,4)
      connected lvt (4(2).8(4)) topology. X-ray diffraction analysis revealed that the
      structures of the MOFs can be mediated by the steric effect of the
      tetracarboxylate and secondary co-ligands. The solid-state luminescence
      properties of the MOFs were measured carefully by ultraviolet irradiation at room
      temperature. In particular, exhibited a high sensitivity for Fe(3+) in aqueous
      solutions of mixed metal ions, which makes it a promising crystalline material to
      be a luminescent probe for Fe(3+). Importantly, can keep its original framework
      and be reused in sensing experiments. The sensing mechanism has also been studied
      in detail. 

PMID- 25974714
TI  - Frustrated Lewis pair chemistry: development and perspectives.
AB  - Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in
      solution that are deterred from strong adduct formation by steric and/or
      electronic factors. This opens pathways to novel cooperative reactions with added
      substrates. Small-molecule binding and activation by FLPs has led to the
      discovery of a variety of new reactions through unprecedented pathways. Hydrogen
      activation and subsequent manipulation in metal-free catalytic hydrogenations is
      a frequently observed feature of many FLPs. The current state of this young but
      rapidly expanding field is outlined in this Review and the future directions for
      its broadening sphere of impact are considered. 

PMID- 25974715
TI  - Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin
      (Corilagin) Rich Extracts of Phyllanthus amarus in Carrageenan-induced Thermal
      and Mechanical Chronic Muscle Hyperalgesia.
AB  - The current study was aimed at evaluating the antihyperalgesic effects of lignans
      (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized
      extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory
      pain. Three percent carrageenan injected in the gastrocnemius muscle produced
      hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the
      contralateral side within 7 to 9 days. To investigate the effects on chronic
      thermal and mechanical hypersensitivity, three extracts of P. amarus in three
      doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally
      from 14th day to 22nd day after intramuscular injection of carrageenan. It was
      observed that intraperitoneal administrations of Phyllanthus extracts showed
      antihyperalgesic activity, as they elevated thermal and mechanical threshold,
      which was supported by histopathological observations along with reduction in
      prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that
      the observed antihyperalgesic and antiinflammatory effects of P. amarus in
      current pain model are mediated via spinal or supraspinal neuronal mechanisms,
      mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be
      due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and
      corilagin, which offers a promising means for treatment of chronic muscle pain.

PMID- 25974716
TI  - Competency Guidelines for Public Health Laboratory Professionals: CDC and the
      Association of Public Health Laboratories.
AB  - These competency guidelines outline the knowledge, skills, and abilities
      necessary for public health laboratory (PHL) professionals to deliver the core
      services of PHLs efficiently and effectively. As part of a 2-year workforce
      project sponsored in 2012 by CDC and the Association of Public Health
      Laboratories (APHL), competencies for 15 domain areas were developed by experts
      representing state and local PHLs, clinical laboratories, academic institutions,
      laboratory professional organizations, CDC, and APHL. The competencies were
      developed and reviewed by approximately 170 subject matter experts with diverse
      backgrounds and experiences in laboratory science and public health. The
      guidelines comprise general, cross-cutting, and specialized domain areas and are
      divided into four levels of proficiency: beginner, competent, proficient, and
      expert. The 15 domain areas are 1) Quality Management System, 2) Ethics, 3)
      Management and Leadership, 4) Communication, 5) Security, 6) Emergency Management
      and Response, 7) Workforce Training, 8) General Laboratory Practice, 9) Safety,
      10) Surveillance, 11) Informatics, 12) Microbiology, 13) Chemistry, 14)
      Bioinformatics, and 15) Research. These competency guidelines are targeted to
      scientists working in PHLs, defined as governmental public health, environmental,
      and agricultural laboratories that provide analytic biological and/or chemical
      testing and testing-related services that protect human populations against
      infectious diseases, foodborne and waterborne diseases, environmental hazards,
      treatable hereditary disorders, and natural and human-made public health
      emergencies. The competencies support certain PHL workforce needs such as
      identifying job responsibilities, assessing individual performance, and providing
      a guiding framework for producing education and training programs. Although these
      competencies were developed specifically for the PHL community, this does not
      preclude their broader application to other professionals in a variety of
      different work settings. 

PMID- 25974717
TI  - The influence of a novel in-office tooth whitening procedure using an Er,Cr:YSGG
      laser on enamel surface morphology.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this in vitro study was to evaluate the
      influence of a novel in-office tooth whitening procedure using Er,Cr:YSGG laser
      radiation on bovine enamel. STUDY DESIGN/MATERIALS AND METHODS: Forty-eight
      enamel specimens were prepared from bovine canines and divided into four groups:
      Group 1 specimens (control) received no whitening treatment; Group 2 received
      whitening treatment with an at-home whitening agent (22% carbamide peroxide) for
      7 days; Group 3 received whitening treatment with a novel in-office whitening
      agent (35% H(2)O(2)); Group 4 received the same in-office whitening therapy with
      Group 3 using Er,Cr:YSGG laser in order to accelerate the whitening procedure.
      The specimens were stored for 10 days after the whitening treatment in artificial
      saliva. Vickers hardness was determined using a microhardness tester and surface
      roughness was evaluated using a VSI microscope. Three specimens of each
      experimental group were examined under SEM and the mineral composition of the
      specimens was evaluated using EDS. Data were statistically analyzed using one-way
      ANOVA, Tukey's post-hoc test, Wilcoxon signed rank and Kruskal-Wallis tests (a =
      0.05). RESULTS: The surface microhardness of the enamel was reduced after the in
      office whitening treatments (P< 0.05), but not influenced after the at-home
      whitening treatment (P> 0.05). Moreover, the surface roughness was not
      significantly changed after tooth whitening. EDS analysis did not show
      alterations in the enamel mineral composition, while SEM observations indicated
      changes in the surface morphology, especially after in-office tooth whitening (P<
      0.05). CONCLUSIONS: The laser-assisted whitening treatment with Er,Cr:YSGG laser
      did not affect the alterations in enamel surface compared with the conventional
      in-office whitening technique.

PMID- 25974718
TI  - GLI2 mutations typically result in pituitary anomalies with or without postaxial
      polydactyly.

PMID- 25974719
TI  - In Patients With Idiopathic Normal Pressure Hydrocephalus Postoperative Cerebral
      Perfusion Changes Measured by Dynamic Susceptibility Contrast Magnetic Resonance
      Imaging Correlate With Clinical Improvement.
AB  - OBJECTIVE: To explore relationships between clinical improvement and relative
      cerebral blood flow (rCBF) changes after shunt-insertion in idiopathic normal
      pressure hydrocephalus (iNPH) as measured by dynamic susceptibility contrast
      magnetic resonance imaging. METHODS: In 20 idiopathic normal pressure
      hydrocephalus patients rCBF was measured preoperatively and 3 months
      postoperatively. Because of shunt-induced right-sided artefacts, evaluation was
      restricted to 12 left-sided cortical, subcortical, and periventricular regions of
      interest. Correlations between rCBF and clinical symptoms were analyzed in shunt
      responders. RESULTS: In responders, the postoperative regions of interest-based
      rCBF increase of 2% to 9% was significant in the parenchyma, the hippocampus, and
      the anterior periventricular white matter. Perfusion improvement in the cingulus,
      caudate head, and thalamus correlated with decreased disturbance in one or more
      of the domains neuropsychology, gait, balance, and total performance.
      CONCLUSIONS: Apparently, dynamic susceptibility contrast magnetic resonance
      imaging can measure postoperative perfusion changes in responders.
      Postoperatively, perfusion increase in some grey matter structures seems to
      determine the degree of clinical improvement.

PMID- 25974720
TI  - Computed Tomography Assessment of Ablation Zone Enhancement in Patients With
      Early-Stage Lung Cancer After Stereotactic Ablative Radiotherapy.
AB  - INTRODUCTION: Stereotactic ablative radiotherapy (SABR) offers a curative
      treatment for lung cancer in patients who are marginal surgical candidates.
      However, unlike traditional surgery the lung cancer remains in place after
      treatment. Thus, imaging follow-up for evaluation of recurrence is of paramount
      importance. MATERIALS AND METHODS: In this retrospective designed Institutional
      Review Board-approved study, follow-up contrast-enhanced computed tomography (CT)
      exams were performed on sixty one patients to evaluate enhancement pattern in the
      ablation zone at 1, 3, 6, and 12 months after SABR. RESULTS: Eleven patients had
      recurrence within the ablation zone after SABR. The postcontrast enhancement in
      the recurrence group showed a washin and washout phenomenon, whereas the
      radiation-induced lung injury group showed continuous enhancement suggesting an
      inflammatory process. CONCLUSIONS: The textural feature of the ablation zone of
      enhancement and perfusion as demonstrated in computed tomography nodule
      enhancement may allow early differentiation of recurrence from radiation-induced
      lung injury in patients' status after SABR or primary lung cancer.

PMID- 25974721
TI  - Noise-robust recognition of wide-field motion direction and the underlying neural
      mechanisms in Drosophila melanogaster.
AB  - Appropriate and robust behavioral control in a noisy environment is important for
      the survival of most organisms. Understanding such robust behavioral control has
      been an attractive subject in neuroscience research. Here, we investigated the
      processing of wide-field motion with random dot noise at both the behavioral and
      neuronal level in Drosophila melanogaster. We measured the head yaw optomotor
      response (OMR) and the activity of motion-sensitive neurons, horizontal system
      (HS) cells, with in vivo whole-cell patch clamp recordings at various levels of
      noise intensity. We found that flies had a robust sensation of motion direction
      under noisy conditions, while membrane potential changes of HS cells were not
      correlated with behavioral responses. By applying signal classification theory to
      the distributions of HS cell responses, however, we found that motion direction
      under noise can be clearly discriminated by HS cells, and that this
      discrimination performance was quantitatively similar to that of OMR.
      Furthermore, we successfully reproduced HS cell activity in response to noisy
      motion stimuli with a local motion detector model including a spatial filter and
      threshold function. This study provides evidence for the physiological basis of
      noise-robust behavior in a tiny insect brain. 

PMID- 25974723
TI  - Lipid-based nutrient supplements do not affect efavirenz but lower plasma
      nevirapine concentrations in Ethiopian adult HIV patients.
AB  - OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV
      programmes in resource-limited settings. However, the possible effects of LNSs on
      the plasma concentrations of antiretroviral drugs have not been assessed. Here,
      we aimed to assess the effects of LNSs on plasma efavirenz and nevirapine trough
      concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of
      LNSs were studied in adults initiating antiretroviral therapy (ART) in a
      randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282)
      received daily supplementation of an LNS containing whey (LNS/w), an LNS
      containing soy (LNS/s) or no LNS. Trough plasma concentrations of efavirenz and
      nevirapine were measured at 1 and 2 months. Genotyping for 516 G>T and 983 T>C
      polymorphisms of the cytochrome P450 (CYP) 2B6 locus was performed. Multilevel
      linear mixed-effects models were used to assess the associations between LNS and
      plasma efavirenz and nevirapine concentrations. RESULTS: In patients with BMI >
      17 kg/m(2), nevirapine concentrations were lower in the LNS/w and LNS/s groups by
      a median of -2.3 MUg/mL [interquartile range (IQR) -3.9; -0.9 MUg/mL; P = 0.002]
      and -2.1 MUg/mL (IQR -3.9; -0.9 MUg/mL; P = 0.01), respectively, compared with
      the group not receiving supplements. There were no differences between groups
      with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism
      was associated with a 5 MUg/mL higher plasma efavirenz concentration compared
      with the wild type (P < 0.0001), while it was not associated with plasma
      nevirapine concentrations. CONCLUSIONS: Intake of an LNS was associated with
      lower plasma nevirapine trough concentrations, indicating possible drug-LNS
      interactions. The clinical relevance of such reductions in nevirapine exposure is
      not clear. Plasma efavirenz concentration was not affected by the LNS.

PMID- 25974722
TI  - Cost-effectiveness analysis of sofosbuvir compared to current standard treatment
      in Swiss patients with chronic hepatitis C.
AB  - In clinical trials, sofosbuvir showed high antiviral activity in patients
      infected with hepatitis C virus (HCV) across all genotypes. We aimed to determine
      the cost-effectiveness of sofosbuvir-based treatment compared to current standard
      treatment in mono-infected patients with chronic hepatitis C (CHC) genotypes 1-4
      in Switzerland. Cost-effectiveness was modelled from the perspective of the Swiss
      health care system using a lifetime Markov model. Incremental cost-effectiveness
      ratios (ICERs) used an endpoint of cost per quality-adjusted life year (QALY)
      gained. Treatment characteristics, quality of life, and transition probabilities
      were obtained from published literature. Country-specific model inputs such as
      patient characteristics, mortality and costs were obtained from Swiss sources. We
      performed extensive sensitivity analyses. Costs and effects were discounted at 3%
      (range: 0-5%) per year. Sofosbuvir-containing treatment in mixed cohorts of
      cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 showed ICERs between
      CHF 10,337 and CHF 91,570 per QALY gained. In subgroup analyses, sofosbuvir
      dominated telaprevir- and boceprevir-containing treatment in treatment-naive
      genotype 1 cirrhotic patients. ICERs of sofosbuvir were above CHF 100,000 per
      QALY in treatment-naive, interferon eligible, non-cirrhotic patients infected
      with genotypes 2 or 3. In deterministic and probabilistic sensitivity analyses,
      results were generally robust. From a Swiss health care system perspective,
      treatment of mixed cohorts of cirrhotic and non-cirrhotic patients with CHC
      genotypes 1-4 with sofosbuvir-containing treatment versus standard treatment
      would be cost-effective if a threshold of CHF 100,000 per QALY was assumed. 

PMID- 25974724
TI  - Highly diastereoselective and enantioselective formal [4 + 3] cycloaddition of
      donor-acceptor cyclobutanes with nitrones.
AB  - The first highly diastereoselective and enantioselective catalytic formal [4 + 3]
      cycloaddition of 1,1-cyclobutane diester with nitrone has been developed.
      Sterically hindered chiral SaBOX/Cu(II) complex promotes the reaction efficiently
      with a broad substrate scope, producing a range of multifunctionalized optically
      active 1,2-oxazepanes with excellent stereocontrol (up to >99/1 dr and 97% ee). 

PMID- 25974725
TI  - Optimizing use of the structural chemical analyser (variable pressure FESEM-EDX
      Raman spectroscopy) on micro-size complex historical paintings characterization.
AB  - The novel Structural Chemical Analyser (hyphenated Raman spectroscopy and
      scanning electron microscopy equipped with an X-ray detector) is gaining
      popularity since it allows 3-D morphological studies and elemental, molecular,
      structural and electronic analyses of a single complex micro-sized sample without
      transfer between instruments. However, its full potential remains unexploited in
      painting heritage where simultaneous identification of inorganic and organic
      materials in paintings is critically yet unresolved. Despite benefits and
      drawbacks shown in literature, new challenges have to be faced analysing
      multifaceted paint specimens. SEM-Structural Chemical Analyser systems differ
      since they are fabricated ad hoc by request. As configuration influences the
      procedure to optimize analyses, likewise analytical protocols have to be designed
      ad hoc. This paper deals with the optimization of the analytical procedure of a
      Variable Pressure Field Emission scanning electron microscopy equipped with an X
      ray detector Raman spectroscopy system to analyse historical paint samples. We
      address essential parameters, technical challenges and limitations raised from
      analysing paint stratigraphies, archaeological samples and loose pigments. We
      show that accurate data interpretation requires comprehensive knowledge of
      factors affecting Raman spectra. We tackled: (i) the in-FESEM-Raman spectroscopy
      analytical sequence, (ii) correlations between FESEM and Structural Chemical
      Analyser/laser analytical position, (iii) Raman signal intensity under different
      VP-FESEM vacuum modes, (iv) carbon deposition on samples under FESEM low-vacuum
      mode, (v) crystal nature and morphology, (vi) depth of focus and (vii) surface
      enhanced Raman scattering effect. We recommend careful planning of analysis
      strategies prior to research which, although time consuming, guarantees reliable
      results. The ultimate goal of this paper is to help to guide future users of a
      FESEM-Structural Chemical Analyser system in order to increase applications. 

PMID- 25974726
TI  - Clinical course, laboratory parameters and outcome of TTP pediatric patients
      presenting with posterior reversible encephalopathy syndrome.
AB  - AIM: The clinical course and outcome of children with thrombotic thrombocytopenic
      purpura and posterior reversible encephalopathy has not been observed and studied
      till date. The aim of the present study was to know the clinical course and
      outcome of children with thrombotic thrombocytopenic purpura and posterior
      reversible encephalopathy. Results from our observation invite potential insight
      for further research on this subject. METHODS: From January 2005 to February
      2013, seven children diagnosed with thrombotic thrombocytopenic purpura and
      posterior reversible encephalopathy syndromes were admitted in a tertiary care
      hospital in Srinagar, Kashmir. The demographic parameters, clinical
      characteristics and laboratory data were noted. The outcome was defined in the
      form of complete recovery or death. Thrombotic thrombocytopenic purpura was
      diagnosed on clinical grounds, laboratory parameters and renal biopsy. The
      diagnosis was established after an expert opinion from a hematologist. Posterior
      reversible encephalopathy syndrome was defined on neuroimaging. RESULTS: The
      common clinical parameters which were shared by all the patients were
      hypertension and altered sensorium. Four (57.1%) patients showed clinical
      deterioration and died within one week of admission even after intensive
      management. Three (42.8%) patients improved clinically and recovered fully and
      were discharged in stable clinical condition. Repeat imaging on discharge was
      normal. CONCLUSION: This series of seven pediatric patients is the first series
      on this subject. The presence of posterior reversible encephalopathy syndrome in
      pediatric patients with thrombotic thrombocytopenic purpura complicates the
      clinical course and worsens the prognosis.

PMID- 25974727
TI  - Urinary metabolomic strategy to evaluate Compound Danshen Dripping Pills for
      myocardial ischaemia in rats.
AB  - Compound Danshen Dripping Pill (CDDP) has been used for the treatment of coronary
      heart disease for decades. We aimed to increase the understanding of the
      mechanisms by evaluating the urinary metabolomics of CDDP using Gas
      Chromatography-Mass Spectrometer (GC-MS) in a myocardial ischaemia (MI) rat
      model. One hundred Sprague-Dawley rats were divided into Con (normal saline and
      no surgery), Con+ (107 mg/kg d CDDP solution and no surgery), Sham (normal saline
      and surgery without aorta ligation), Mod (normal saline and surgery with aorta
      ligation), and Mod+ (107 mg/kg d CDDP solution and surgery with aorta ligation)
      groups. Urine samples on days 0, 3, 14, and 28 were tested using GC-MS and
      analyzed with PCA and partial least squares-discriminant analysis models. In the
      Mod group, creatine kinase and malondialdehyde levels were higher, and superoxide
      dismutase levels were lower; the same variables normalized in the Mod+ group.
      CDDP resulted in improvement in the Mod+ group, as indicated by the reduced
      necrosis in the myocardial tissue. A total of 36 metabolites were identified in
      the urine samples, and 8 metabolites (malate, succinate, creatinine, methionine,
      cysteine, serine, phenylalanine, and tyrosine) were increased remarkably and
      recovered to normal levels after treatment with CDDP. Differentially expressed
      metabolites implied that energy, amino acid, fatty acid, and polyol metabolism
      might be disrupted by MI and reversed by CDDP. Urinary metabolomics provide a
      dynamic monitoring approach that highlights interference by MI and the
      therapeutic effects of CDDP on MI in rats throughout the recovery process.

PMID- 25974728
TI  - Solvent-Induced Change of Electronic Spectra and Magnetic Susceptibility of
      Co(II) Coordination Polymer with 2,4,6-Tris(4-pyridyl)-1,3,5-triazine.
AB  - One-dimensional coordination polymer [Co(Piv)2(4-ptz)(C2H5OH)2]n (compound 1,
      Piv(-) = pivalate, 4-ptz = 2,4,6-tris(4-pyridyl)-1,3,5-triazine) was synthesized
      by interaction of Co(II) pivalate with 4-ptz. Desolvation of 1 led to formation
      of [Co(Piv)2(4-ptz)]n (compound 2), which adsorbed N2 and H2 at 78 K as a typical
      microporous sorbent. In contrast, absorption of methanol and ethanol by 2 at 295
      K led to structural transformation probably connected with coordination of these
      alcohols to Co(II). Formation of 2 from 1 was accompanied by change of color of
      sample from orange to brown and more than 2-fold decrease of molar magnetic
      susceptibility (chiM) in the temperature range from 2 to 300 K. Resolvation of 2
      by ethanol or water resulted in restoration of spectral characteristics and chiM
      values almost to the level of that of 1. chiMT versus T curves for 1 and samples,
      obtained by resolvation of 2 by H2O or C2H5OH, were fitted using a model for
      Co(II) complex with zero-field splitting of this ion. 

PMID- 25974729
TI  - Life after the Liverpool Care Pathway (LCP): a qualitative study of critical care
      practitioners delivering end-of-life care.
AB  - AIM: To explore the experiences, challenges and practices of critical care
      practitioners since the discontinuation of the Liverpool Care Pathway in critical
      care settings. BACKGROUND: The Liverpool Care Pathway was widely used with an aim
      to improve communication and care for dying individuals and their relatives.
      However, widespread media criticism prompted a review, which resulted in the
      discontinuation of the Liverpool Care Pathway across all UK clinical settings.
      DESIGN: A qualitative study. METHOD: The study was carried out in two large acute
      hospitals in England. Semi-structured interviews were conducted with 14 critical
      care practitioners, 6 months after discontinuation of the Liverpool Care Pathway.
      Transcribed verbatim data were analysed using framework analysis. RESULTS: Three
      key themes emerged: 'lessons learned', 'uncertainties and ambivalences' and 'the
      future'. Critical care practitioners reported that life after the Liverpool Care
      Pathway in critical care settings often involved various clinical ambivalences,
      uncertainties and inconsistencies in the delivery of end-of-life care, especially
      for less experienced practitioners. Critical care practitioners had 'become
      accustomed' to the components of the Liverpool Care Pathway, which still guide
      them in principle to ensure quality end-of-life care. The Liverpool Care
      Pathway's structured format was perceived to be a useful clinical tool, but was
      also criticized as a 'tick-box exercise' and for lacking in family involvement.
      CONCLUSIONS: This study posits two key conclusions. Despite experienced critical
      care practitioners being able to deliver quality end-of-life care without using
      the Liverpool Care Pathway, junior nursing and medical staff need clear
      guidelines and support from experienced mentors in practice. Evidence-based
      guidelines related to family involvement in end-of-life care planning in critical
      care settings are also needed to avoid future controversies.

PMID- 25974730
TI  - Posterior tibial nerve stimulation for the treatment of fecal incontinence: a
      systematic evidence review.
AB  - IMPORTANCE AND OBJECTIVES: Posterior tibial nerve stimulation (PTNS) is a
      potential emerging therapy for fecal incontinence (FI). The aim of this study was
      to systematically review the literature regarding the efficacy of PTNS as a
      treatment of FI. EVIDENCE ACQUISITION: We searched MEDLINE/PubMed, EMBASE, and
      Cochrane databases from inception through November 2013. We included English
      language full-text articles reporting outcomes for FI with either percutaneous
      PTNS or transcutaneous techniques (transcutaneous electrical nerve stimulation).
      We used the Grades of Recommendation, Assessment, Development, and Evaluation
      (GRADE) system to assess study quality. RESULTS: Our search yielded 1154
      citations; 129 abstracts and 17 articles were included for full-text review.
      There were 13 case series and 4 randomized controlled trials. Fifteen studies
      were of low quality, none were of fair quality, and 2 studies were of good
      quality based on the Grades of Recommendation, Assessment, Development, and
      Evaluation system. In total, 745 subjects were studied, and of those, 90% were
      women and 10% were men. Studies involved percutaneous PTNS in 57% (428/745) of
      the subjects, transcutaneous electrical nerve stimulation in 30% (223/745), and
      sham technique in 13% (94/745). Therapy frequency, maintenance therapy, and
      follow-up time varied across studies. Eleven studies assessed FI episodes and
      bowel movement deferment time; all but 1 showed statistical improvement after
      therapy. Ten of the 11 studies that used the Cleveland Clinic Florida Fecal
      Incontinence score reported statistically significantly improved scores after
      treatment. CONCLUSIONS AND RELEVANCE: Multiple low-quality studies show
      improvement in FI after PTNS. High-quality studies with comparison groups and
      clinically meaningful outcome measures would further establish the utility of
      PTNS for FI.

PMID- 25974731
TI  - Iron deficiency anemia in women: a practical guide to detection, diagnosis, and
      treatment.
AB  - INTRODUCTION: Iron deficiency anemia (IDA) remains a widely underdiagnosed and
      unappreciated women's health issue, affecting women of all ages. Despite the fact
      that IDA is easily diagnosed and treated, it continues to be a major public
      health issue. The World Health Organization estimates that 30% of nonpregnant and
      more than 42% of pregnant women have anemia. METHODS: A multidisciplinary Group
      for the Research and Education on Anemia Therapy in Women (GREAT Women II) was
      formed, sponsored by the Society for the Advancement of Blood Management. The
      goal was to focus attention on the impact of IDA on women at various stages of
      life and evaluate and use published literature to provide a simple, evidence
      based approach to diagnose and treat IDA. RESULTS: The group developed specific
      recommendations for evaluating and treating IDA in women. Initial diagnosis is
      defined as hemoglobin less than 12 g/dL in nonpregnant women. A trial of iron
      therapy (4 weeks) can be considered a first-line diagnostic tool. Alternatively,
      a low or normal mean corpuscular volume (<100 fL), low serum ferritin (<30
      MUg/L), and/or low transferrin saturation (transferrin saturation <20%) is
      sufficient to confirm IDA. If the patient does not fit the diagnosis of IDA or
      fails to respond to a trial of oral iron, or mean corpuscular volume is elevated,
      further diagnostic evaluation is needed, including iron studies, B12, folate
      levels, and renal function tests. If results are not definitive, and IDA
      persists, a hematology referral is recommended. CONCLUSION: Clinicians should
      routinely identify and treat IDA, thereby decreasing its negative impact on
      health and quality of life of women.

PMID- 25974732
TI  - The role of episiotomy in prevention and management of shoulder dystocia: a
      systematic review.
AB  - IMPORTANCE: Shoulder dystocia is an obstetric emergency with potential
      catastrophic outcomes. OBJECTIVE: To perform a systematic literature review
      examining the effectiveness of episiotomy in the prevention and management of
      shoulder dystocia during vaginal birth. EVIDENCE ACQUISITION: Search was
      conducted by a research librarian in MEDLINE, Web of Science, Cochrane Library,
      and SCOPUS databases using the terms "episiotomy" and "shoulder dystocia," with
      no language or time restrictions. Two investigators independently selected
      original researches examining the effects of episiotomy on shoulder dystocia and
      its neonatal andmaternal outcomes. Relevant articles were accessed in full text,
      including manual search of the references. We contacted authors of studies with
      insufficient or unclear data. Because of clinical and methodological diversity of
      the studies, meta-analysis was not performed. RESULTS: Fourteen articles met the
      inclusion criteria, encompassing a total of 9769 shoulder dystocia cases. Only 1
      study effectively evaluated the role of episiotomy in shoulder dystocia
      prevention, yielding a nonsignificant result. Three articles assessed neonatal
      consequences of shoulder dystocia, one of them linking episiotomy to higher risk
      of neonatal injury. Two of the 3 studies evaluating maternal outcomes showed that
      episiotomy is related to increased risk of advanced perineal tears. Overall
      quality of evidence was rated as very low. CONCLUSIONS AND RELEVANCE: Our
      systematic review found no evidence supporting the use of episiotomy in the
      prevention and management of shoulder dystocia. This observation carries major
      clinical and legal implications for the obstetricians. Higher-quality studies are
      needed to evaluate this important issue.

PMID- 25974733
TI  - Seeing red: How perceptions of social status and worth influence hostile
      attributions and endorsement of aggression.
AB  - Within social hierarchies, low social status is associated with increased
      vigilance, hostile expectations, and reactive aggression. We propose that
      societal devaluation is common across many low social status groups and produces
      a sense of threatened social worth. Threatened social worth may lead those of low
      status to be more vigilant towards social threats, thereby increasing the
      likelihood of hostile attributions and endorsement of aggression. Integrating
      theory on belongingness, social rejection, and stigma compensation, two studies
      test a sequential process model demonstrating that threatened social worth
      mediates the relationship between status, hostile attributions, and endorsement
      of aggression. Employing a relative status manipulation, Study 2 reveals a causal
      effect of status and highlights the importance of perceptions of low social
      status on threatened social worth. These data demonstrate the role of social
      worth in explaining the link between status and hostility and have implications
      for research in the social, health, and developmental domains. 

PMID- 25974734
TI  - High Postnatal Growth Hormone Levels Are Related to Cognitive Deficits in a Group
      of Children Born Very Preterm.
AB  - CONTEXT AND OBJECTIVES: Little is known regarding the influence of GH on brain
      development, especially in infants born very preterm (VP; <30 weeks' gestation).
      Preterm infants are thought to have higher levels of GH in the first days of life
      compared with full-term infants. VP infants experience cognitive difficulties in
      childhood and have a diffuse pattern of structural brain abnormalities. This
      study aimed to explore the relationship between postnatal GH concentrations
      following VP birth and its association with cognitive functioning and brain
      volumes at age 7 years. METHODS: Eighty-three infants born VP had GH
      concentrations measured at eight time points postnatally, and 2- and 6-week area
      under the curve (AUC) summary measures were calculated. Followup at age 7 years
      included neuropsychological assessment and brain magnetic resonance imaging.
      Univariable and multivariable regression modeling were used where AUC for GH was
      the main predictor of neurodevelopmental outcome at age 7 years. RESULTS:
      Univariable modeling revealed that higher GH levels (2-week AUC) were related to
      poorer performance on a verbal working memory (P = .04) and shifting attention
      task (P = .01). These relationships persisted on multivariable modeling and when
      the 6-week AUC was analyzed; working memory (P = .03), immediate spatial memory
      (P = .02), and delayed spatial memory (P = .03) deficits were found. Higher GH
      levels were also associated with larger amygdala volumes after adjustment for
      potential confounders (P = .002, 2-week AUC; P = .03, 6-week AUC). CONCLUSIONS:
      Higher postnatal GH levels may potentially contribute to the documented
      neurodevelopmental abnormalities seen in children born VP at school age.

PMID- 25974735
TI  - Role of X-Linked Inhibitor of Apoptosis as a Prognostic Marker and Therapeutic
      Target in Papillary Thyroid Carcinoma.
AB  - CONTEXT: Papillary thyroid cancer (PTC) is the second most common cancer in
      females in Saudi Arabia. However, the pathogenesis of PTC is still not fully
      elucidated. OBJECTIVE: To identify potential genes that play important role in
      progression of PTC, we studied the role of X-linked inhibitor of apoptosis
      protein (XIAP) as a potential prognostic marker and therapeutic target in a large
      cohort of PTC samples and cell lines. DESIGN: A DNA microarray chip was used to
      screen for gene copy number. XIAP expression was assessed by immunohistochemistry
      in a tissue microarray format on a cohort of 1022 clinical samples. In vitro and
      in vivo studies were performed using Embelin and/or LY294002 on PTC cell lines.
      RESULTS: XIAP was found to be amplified in 14 of 29 and overexpressed in 48.8% of
      PTC cases. XIAP overexpression was significantly associated with old age,
      extrathyroidal extension, tumor size, nodal involvement, tall-cell variant,
      advanced stage disease, and significantly poor disease-free survival (P = .0341).
      XIAP was also significantly associated with phosphorylated AKT (P < .0001), Bcl
      Xl (P < .0001), and Ki67 (P = .0006) proteins. Embelin treatment caused growth
      inhibition and apoptosis in PTC cell lines and induced tumor regression in PTC
      xenograft in nude mice. Finally, the combination of suboptimal doses of Embelin
      and LY294002 induced a synergistic apoptotic response in PTC cells. CONCLUSION:
      XIAP dysregulation in PTC confers an aggressive phenotype with poor outcome. In
      vitro and in vivo studies using an XIAP inhibitor suggest that this subgroup of
      PTC with overexpression of XIAP can be therapeutically targeted, either alone or
      in combination, to induce efficient apoptosis in these cancers.

PMID- 25974736
TI  - Severe Obesity in Adolescents and Young Adults Is Associated With Subclinical
      Cardiac and Vascular Changes.
AB  - CONTEXT: Severe obesity is the fastest growing subgroup of obesity in youth.
      OBJECTIVE: We sought to explore the association between severe obesity and
      subclinical measures of cardiac and vascular structure and function in
      adolescents and young adults. DESIGN, SETTING, AND PARTICIPANTS: This was a cross
      sectional comparison of 265 adolescents and young adults with severe obesity
      (defined as body mass index [BMI] >=120% of the 95th percentile) to 182
      adolescents and young adults with obesity (defined as BMI >=100-119th of the 95th
      percentile) at tertiary medical center. MAIN OUTCOMES: Noninvasive measures of
      cardiac and vascular structure and function were assessed. RESULTS: Participants
      were a mean age of 17.9 years, 62% were non-Caucasian, and 68% were female.
      Systolic blood pressure, fasting insulin, C-reactive protein, IL-6, and frequency
      of type 2 diabetes were higher in participants with severe obesity (all P < .05).
      Arterial thickness and stiffness, cardiac structure, and diastolic function were
      also significantly worse in youth with severe obesity as measured by higher left
      ventricular mass index, worse diastolic function, higher carotid intima media
      thickness, and pulse wave velocity and lower brachial distensibility (all P <
      .05). Regression modeling showed that severe obesity (compared with obesity) was
      independently associated with each of the above outcomes after adjustment for
      age, race, sex, blood pressure, lipids, and inflammatory markers (P < .05).
      CONCLUSIONS: Adolescents and young adults with severe obesity have a more adverse
      cardiovascular risk profile and worse cardiac and vascular structure and
      function. More importantly, severe obesity is independently associated with these
      subclinical cardiac and vascular changes.

PMID- 25974737
TI  - Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients
      With Essential Hypertension.
AB  - CONTEXT: Aldosterone (ALD) secretion is regulated mainly by angiotensin II, K(+),
      and adrenocorticotropic hormone (ACTH). Mineralocorticoid receptor antagonists
      (MRAs) have effectively been used for the treatment of patients with hypertension
      who do not have primary aldosteronism (PA). OBJECTIVE: We tested whether chronic
      stress-related ACTH-mediated ALD hypersecretion and/or zona glomerulosa
      hypersensitivity could be implicated in the pathogenesis of essential
      hypertension (ESHT). PATIENTS AND METHODS: One hundred thirteen hypertensives
      without PA and 61 normotensive controls underwent an ultralow-dose (0.03-MUg)
      ACTH stimulation and a treadmill test. Patients with ALD hyper-response according
      to the cutoffs obtained from controls received treatment with MRAs and underwent
      genomic DNA testing for the presence of the CYP11B1/CYP11B2 chimeric gene and
      KCNJ5 gene mutations. A control group of 22 patients with simple ESHT received
      treatment with MRAs. RESULTS: Based on the cutoffs of ALD and aldosterone-to
      renin ratio (ARR) post-ACTH stimulation obtained from controls, 30 patients (27%)
      exhibited an ALD but not cortisol (F) hyper-response (HYPER group). This group
      had no difference in basal ACTH/renin (REN) concentrations compared with controls
      and the 83 patients with hypertension (73%) without an ALD hyper-response to ACTH
      stimulation. Patients in the HYPER group demonstrated significantly higher ALD
      concentrations, ARR, and ALD/ACTH ratio (AAR) in the treadmill test. Treatment
      with MRAs alone produced normalization of blood pressure in these patients
      whereas patients with hypertension with neither PA nor ALD hyper-response to ACTH
      stimulation who served as a control group failed to lower blood pressure. Also,
      two novel germline heterozygous KCNJ5 mutations were detected in the HYPER group.
      CONCLUSIONS: A number of patients with hypertension without PA show ACTH
      dependent ALD hyper-secretion and benefit from treatment with MRAs. This could be
      related to chronic stress via ACTH hyper secretion and/or gene-mutations
      increasing the zona glomerulosa responsiveness to excitatory stimuli.

PMID- 25974738
TI  - Extraordinary capability for water treatment achieved by a perfluorous conjugated
      microporous polymer.
AB  - Oils, organic solvents, dyes, and heavy metal ions are primary pollutants in
      water resources. Currently, no sorbent material can effectively remove these
      types of pollutants simultaneously. Here we report a perfluorous conjugated
      microporous polymer with superhydrophobicity and a large surface area, which
      exhibits outstanding adsorption capacities, kinetics, and recyclability for a
      wide range of organic solvents, oils, dyes, and heavy metal ions. The adsorption
      capacities of this polymer, 1376.7 mg g(-1) for Congo red, 808.2 mg g(-1) for
      Pb(II) and 303.2 mg g(-1) for As(V), are higher than the adsorption capacities of
      any previously described porous materials. Our theoretical calculation reveals
      that the superior properties of this polymer are due to fluorination and triple
      bonds within the polymer. A benchmark experiment indicates that this polymer can
      efficiently remove these pollutants simultaneously. Application of this polymer
      may lead to the development of next-generation reusable and portable water
      purification appliances. 

PMID- 25974739
TI  - Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor
      Release.
AB  - Histone deacetylase inhibitors (HDACi) target abnormal epigenetic states
      associated with a variety of pathologies, including cancer. Here, the development
      of a prodrug of the canonical broad-spectrum HDACi suberoylanilide hydroxamic
      acid (SAHA) is described. Although hydroxamic acids are utilized universally in
      the development of metalloenzyme inhibitors, they are considered to be poor
      pharmacophores with reduced activity in vivo. We developed a prodrug of SAHA by
      appending a promoiety, sensitive to thiols, to the hydroxamic acid warhead
      (termed SAHA-TAP). After incubation of SAHA-TAP with an HDAC, the thiol of a
      conserved HDAC cysteine residue becomes covalently tagged with the promoiety,
      initiating a cascade reaction that leads to the release of SAHA. Mass
      spectrometry and enzyme kinetics experiments validate that the cysteine residue
      is covalently appended with the TAP promoiety. SAHA-TAP demonstrates cytotoxicity
      activity against various cancer cell lines. This strategy represents an original
      prodrug design with a dual mode of action for HDAC inhibition. 

PMID- 25974741
TI  - Prediction intervals: Placing real bounds on regression-based allometric
      estimates of biomass.
AB  - Biomass allometry studies routinely assume that regression models can be applied
      across species and sites, and that goodness of fit of a regression model to its
      derivation dataset indicates both the relevance of the model to a new dataset and
      the likely error. Assuming that a model is relevant for a new sample, a
      prediction interval is a useful error measure for stand mass. Prediction coverage
      tests whether the model and hence the interval are appropriate in the new sample.
      Data for three similar shrubby species from four similar sites were combined in
      various ways to test the impact of varying levels of biodiverse heterogeneity on
      the performance of the four models most commonly used in published biomass
      studies. No one model performed consistently well predicting new data, and
      validation checks were not good indicators of prediction coverage. The highly
      variable results suggest that the common models might contain insufficient
      variables. Euclidean distance was used to quantify the relative similarity of
      samples as a possible means of estimating prediction coverage; it proved
      unsuccessful with these data. 

PMID- 25974740
TI  - Escherichia coli O157:H7 Outbreak Associated with the Consumption of Beef and
      Veal Tartares in the Province of Quebec, Canada, in 2013.
AB  - OBJECTIVES: An Escherichia coli O157:H7 outbreak occurred in 2013 that was
      associated with the consumption of beef and veal tartares in the province of
      Quebec. This report describes the results of the ensuing investigation. MATERIALS
      AND METHODS: As the outbreak was identified, all individuals in the province of
      Quebec affected with the same strain of E. coli O157:H7 as defined by pulsed
      field gel electrophoresis were interviewed using a standardized questionnaire.
      Cases reported from other provinces in Canada were interviewed by their public
      health authorities and the results were reported to the Quebec public health
      authorities. Microbiological and environmental investigations were conducted by
      the Sous-ministeriat a la sante animale et a l'inspection des aliments du
      Ministere de l'Agriculture, des Pecheries et de l'Alimentation du Quebec, by the
      Ville de Montreal's Food Inspection Branch, and by the Canadian Food Inspection
      Agency at the restaurants, suppliers, and slaughterhouses identified. RESULTS: In
      total, seven individuals in three different Canadian provinces became ill
      following infection with the same outbreak strain of E. coli O157:H7. Two cases
      were hospitalized and one had severe hemolytic uremic syndrome. No deaths were
      reported. Two restaurant locations serving different tartare meals including,
      beef, veal, salmon, tuna, and duck were identified as potential sources of the
      outbreak. No deficiencies at the restaurant locations were observed during
      inspections by food inspectors. CONCLUSIONS: The risk of consuming tartare can be
      lowered when basic hygienic rules are followed, temperature is strictly
      controlled, and fresh meat is used. However, even if handling, chopping, and
      temperature control during storage of the meat are considered adequate, tartare
      is a raw product and the risk of contamination is present. Consumers should be
      advised that consuming this product can lead to serious illness.

PMID- 25974742
TI  - Outcome of vulvar reconstruction by anterolateral thigh flap in patients with
      advanced and recurrent vulvar malignancy.
AB  - BACKGROUND: To evaluate the outcomes of vulvar reconstruction using anterolateral
      thigh (ALT) flaps in patients with advanced and recurrent vulvar malignancies.
      METHODS: Totally 24 patients who received ALT-based vulvar reconstruction were
      retrospectively reviewed to evaluate the outcome focusing on quality of life and
      prognosis. RESULTS: Four patients received vulvar reconstruction at the time of
      primary surgery due to advanced stage, and 20 patients underwent vulvar
      reconstruction after recurrence. No patient experienced complete flap loss. Major
      complications happened in five patients (20.83%). Minor complications occurred in
      three patients (12.5%). All wounds healed favorable after appropriate treatment.
      The mean scale of verbal rating scale (VRS-4) was 1.58 before reconstruction
      while decreased to 0.13 after surgery (P < 0.0001). Mean performance status was
      1.67 before surgery compared to 0.13 after surgery (P < 0.0001). Fourteen
      patients (58.33%) developed recurrence with a median interval of recurrence of 5
      months after vulvar reconstruction. Ten patients (41.67%) are living with disease
      free in a median follow-up of 19.5 months. Overall 5 years survival was 56.4%.
      CONCLUSION: ALT flap based vulvar reconstruction method can improve the quality
      of life and might be considered as an appropriate option for reconstructing the
      vulvar defects in patients with advanced or recurrent vulvar malignancy.

PMID- 25974743
TI  - Angiotensin receptor blockers improve survival outcomes after radiofrequency
      ablation in hepatocarcinoma patients.
AB  - BACKGROUND AND AIM: Inhibition of angiotensin II synthesis seems to decrease
      hepatocellular carcinoma recurrence after radical therapies; however, data on the
      adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking.
      The aim of the study was to evaluate whether sartans delay time to recurrence and
      prolong overall survival in hepatocellular carcinoma patients after
      radiofrequency ablation. METHODS: Data on 153 patients were reviewed. The study
      population was classified into three groups: 73 (47.8%) patients who received
      neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 49 (32%)
      patients treated with angiotensin-converting enzyme inhibitors (group 2), and 31
      (20.2%) patients treated with sartans (group 3). Survival outcomes were analysed
      by means of Kaplan-Meier analysis and compared with log-rank test. RESULTS: In
      the whole study population, 85.6% of patients were in Child-Pugh A class and
      89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was
      30 mm (10-40) and alpha fetoprotein was 25 (1.1-2100) UI/mL. No differences in
      baseline characteristics among the three groups were reported. Median overall
      survival was 48 months (95% confidence interval: 31-58) in group 1, 72 months (49
      89) in group 2, and 84 months (58-92) in group 3 (P = 0.02). Median time to
      recurrence was 26 (15-42), 44 (33-72), and 69 (44-74) months in the three groups,
      respectively (P = 0.02). Sartan therapy was a significant predictor of longer
      overall survival and delayed time to recurrence on multivariate analysis.
      CONCLUSION: Sartans significantly improved overall survival and time to
      recurrence after radiofrequency ablation in hepatocellular carcinoma patients.

PMID- 25974744
TI  - Comparison of Plaque Burden and Vessel Remodeling in Obstructive Saphenous Vein
      Graft Lesions as Assessed by Intravascular Ultrasound and Dual-source Computed
      Tomography.
AB  - PURPOSE: The aim of our study was to compare plaque burden and vessel remodeling
      of obstructive saphenous vein graft (SVG) lesions as assessed by dual-source
      computed tomography (DSCT) and intravascular ultrasound (IVUS). MATERIALS AND
      METHODS: Preintervention DSCT examination and IVUS were performed in consecutive
      patients before percutaneous treatment of the SVG lesion. SVG vessel and lumen
      areas were measured with use of DSCT and IVUS at the minimal lumen area (MLA)
      site and at proximal and distal reference sites. Plaque burden was defined as the
      ratio of plaque and vessel area. Remodeling index was defined as the ratio of the
      SVG area at the MLA site to the mean reference SVG area. RESULTS: Twenty-four
      obstructive SVG lesions were imaged with DSCT and IVUS before stent implantation
      in 24 patients. The SVG cross-sectional area at the MLA site measured by IVUS and
      DSCT was similar (17.0+/-4.5 vs. 17.3+/-5.3 mm, P=0.6) and well correlated
      (R=0.77, P<0.001). Similarly, plaque burden and remodeling index assessments did
      not differ significantly between the 2 imaging modalities (79.0%+/-4.0% vs.
      81.0%+/-8.0%, P=0.18, and 1.09+/-0.22 vs. 1.07+/-0.32, P=0.7 for IVUS vs. DSCT
      for plaque burden and remodeling, respectively). The correlation between IVUS
      assessed and DSCT-assessed plaque burden and remodeling index was moderate to
      good (R=0.55, P=0.01 and R=0.77, P<0.001, respectively, for plaque burden and
      remodeling index). CONCLUSIONS: There is moderate to good correlation between
      DSCT and IVUS in the assessment of vessel remodeling and plaque burden in
      obstructive SVG lesions. Noninvasive assessment and monitoring of SVG disease is
      feasible using DSCT.

PMID- 25974746
TI  - Orthopedic asymmetry and clavicle length.

PMID- 25974745
TI  - Experimental approaches to identify small RNAs and their diverse roles in
      bacteria--what we have learnt in one decade of MicA research.
AB  - Nowadays the identification of small RNAs (sRNAs) and characterization of their
      role within regulatory networks takes a prominent place in deciphering complex
      bacterial phenotypes. Compared to the study of other components of bacterial
      cells, this is a relatively new but fast-growing research field. Although reports
      on new sRNAs appear regularly, some sRNAs are already subject of research for a
      longer time. One of such sRNAs is MicA, a sRNA best described for its role in
      outer membrane remodeling, but probably having a much broader function than
      anticipated. An overview of what we have learnt from MicA led to the conclusion
      that even for this well-described sRNA, we still do not have the overall picture.
      More general, the story of MicA might become an experimental lead for unraveling
      the many sRNAs with unknown functions. In this review, three important topics in
      the sRNA field are covered, exemplified from the perspective of MicA: (i)
      identification of new sRNAs, (ii) target identification and unraveling the
      biological function, (iii) structural analysis. The complex mechanisms of action
      of MicA deliver some original insights in the sRNA field which includes the
      existence of dimer formation or simultaneous cis and trans regulation, and might
      further inspire the understanding of the function of other sRNAs. 

PMID- 25974748
TI  - Neurolymphomatosis: MRI and (18) FDG-PET features.
AB  - Neurolymphomatosis (NL) is a rare presentation of lymphoma or leukemic
      infiltration of cranial or peripheral nerves. It is distinct from subarachnoid
      seeding of lymphoma as well as perineural tumour seen in epidural lymphoma. This
      rare condition has been reported mainly in oncology literature. Imaging features
      of solitary nerve involvement mimics, among others, peripheral nerve sheath
      tumours. We present the MRI and (18) fluorodeoxyglucose positron emission
      tomography ((18) FDG-PET) features of three cases of NL. MRI demonstrated
      variable appearances: infiltrative mass displacing neural fascicles, diffuse
      thickening and enhancement, and thickening of individual neural fascicles. (18)
      FDG-PET demonstrated avid uptake in all cases, two of which revealed skip lesions
      of the same nerve. The diagnosis of NL was confirmed by uncomplicated CT-guided
      biopsy of the affected sciatic nerve in one patient. 

PMID- 25974749
TI  - Application of the Stopped Flow Technique to the TiO2-Heterogeneous
      Photocatalysis of Hexavalent Chromium in Aqueous Suspensions: Comparison with O2
      and H2O2 as Electron Acceptors.
AB  - The dynamics of the transfer of electrons stored in TiO2 nanoparticles to Cr(VI)
      in aqueous solution have been investigated using the stopped flow technique. TiO2
      nanoparticles were previously irradiated under UV light in the presence of formic
      acid, and trapped electrons (e(trap)(-)) were made to react with Cr(VI) as
      acceptor species; other common acceptor species such as O2 and H2O2 were also
      tested. The temporal evolution of the number of trapped electrons was followed by
      the decrease in the absorbance at 600 nm, and the kinetics of the electron
      transfer reaction was modeled. Additionally, the rate of formation of the surface
      complex between Cr(VI) and TiO2 was determined with the stopped flow technique by
      following the evolution of the absorbance at 400 nm of suspensions of
      nonirradiated TiO2 nanoparticles and Cr(VI) at different concentrations. An
      approximately quadratic relationship was observed between the maximum absorbance
      of the surface complex and the concentration of Cr(VI), suggesting that Cr(VI)
      adsorbs onto the TiO2 surface as dichromate. The kinetic analyses indicate that
      the electron transfer from TiO2 to Cr(VI) does not require the previous formation
      of the Cr(VI)-TiO2 surface complex, at least the complex detected here through
      the stopped flow experiments. When previously irradiated TiO2 was used to follow
      the evolution of the Cr(VI)-TiO2 complex, an inhibition of the formation of the
      complex was observed, which can be related to the TiO2 deactivation caused by
      Cr(III) deposition.

PMID- 25974747
TI  - Paracrine co-delivery of TGF-beta and IL-2 using CD4-targeted nanoparticles for
      induction and maintenance of regulatory T cells.
AB  - The cytokine milieu is critical for orchestration of lineage development towards
      effector T cell (Teff) or regulatory T cell (Treg) subsets implicated in the
      progression of cancer and autoimmune disease. Importantly, the fitness and
      survival of the Treg subset is dependent on the cytokines Interleukin-2 (IL-2)
      and transforming growth factor beta (TGF-beta). The production of these cytokines
      is impaired in autoimmunity increasing the probability of Treg conversion to
      aggressive effector cells in a proinflammatory microenvironment. Therapy using
      soluble TGF-beta and IL-2 administration is hindered by the cytokines' toxic
      pleiotropic effects and hence bioavailability to CD4(+) T cell targets. Thus,
      there is a clear need for a strategy that rectifies the cytokine milieu in
      autoimmunity and inflammation leading to enhanced Treg stability, frequency and
      number. Here we show that inert biodegradable nanoparticles (NP) loaded with TGF
      beta and IL-2 and targeted to CD4(+) cells can induce CD4(+) Tregs in-vitro and
      expand their number in-vivo. The stability of induced Tregs with cytokine-loaded
      NP was enhanced leading to retention of their suppressive phenotype even in the
      presence of proinflammatory cytokines. Our results highlight the importance of a
      nanocarrier-based approach for stabilizing and expanding Tregs essential for cell
      immunotherapy of inflammation and autoimmune disease. 

PMID- 25974750
TI  - Cachexia and sarcopenia: mechanisms and potential targets for intervention.
AB  - Cachexia is a multi-organ syndrome associated with cancer and other chronic
      diseases, characterized by body weight loss, muscle and adipose tissue wasting
      and inflammation, being often associated with anorexia. Skeletal muscle tissue
      represents more than 40% of body weight and seems to be one of the main tissues
      involved in the wasting that occurs during cachexia. Sarcopenia is a degenerative
      loss of skeletal muscle mass, quality, and strength associated with healthy
      ageing. The molecular mechanisms behind cachexia and sarcopenia share some common
      trends. Muscle wasting is the result of a combination of an imbalance between
      synthetic and degradative protein pathways together with increased myocyte
      apoptosis and decreased regenerative capacity. Oxidative pathways are also
      altered in skeletal muscle during muscle wasting and this seems to be a
      consequence of mitochondrial abnormalities that include altered morphology and
      function, decreased ATP synthesis and uncoupling. The aim of the present review
      is to analyse common molecular pathways between cachexia and sarcopenia in order
      to put forward potential targets for intervention. 

PMID- 25974751
TI  - Sustainable childhood obesity prevention through community engagement (SCOPE)
      program: evaluation of the implementation phase.
AB  - Childhood obesity rates are steadily rising. Sustainable Childhood Obesity
      Prevention Through Community Engagement (SCOPE) is a community-based
      participatory action research (PAR) program aimed at preventing childhood
      obesity. This study aimed to describe community perspectives on, and elicit
      feedback about, SCOPE's first phase of implementation in two pilot cities in
      British Columbia, Canada. A case study was implemented using interviews and
      questionnaires to obtain feedback about SCOPE from two groups: SCOPE coordinators
      and stakeholders (i.e., individuals and organizations that were a member of the
      community and engaged with SCOPE coordinators). Participants were recruited via
      email and (or) by telephone. Coordinators completed a telephone interview.
      Stakeholders completed a questionnaire and (or) a telephone interview. Thematic
      analysis was conducted. Participants included 2 coordinators and 15 stakeholders.
      Participants similarly interpreted SCOPE as a program focused on raising
      awareness about childhood obesity prevention, while engaging multiple community
      sectors. Overall, participants valued the program's role in facilitating
      networking and partnership development, providing evidence-based resources,
      technical expertise, and contributing funding. Participants felt that SCOPE is
      sustainable. However, participants felt that barriers to achieving healthy
      weights among children included those related to the built environment, and
      social, behavioral, and economic obstacles. Perspectives on factors that
      facilitated and acted as barriers to SCOPE's first phase of implementation were
      obtained from the SCOPE communities and may be used to enhance the sustainability
      of SCOPE and its applicability to other BC communities.

PMID- 25974752
TI  - Tracking of dendritic cell migration into lymph nodes using molecular imaging
      with sodium iodide symporter and enhanced firefly luciferase genes.
AB  - We sought to evaluate the feasibility of molecular imaging using the human sodium
      iodide symporter (hNIS) gene as a reporter, in addition to the enhanced firefly
      luciferase (effluc) gene, for tracking dendritic cell (DCs) migration in living
      mice. A murine dendritic cell line (DC2.4) co-expressing hNIS and effluc genes
      (DC/NF) was established. For the DC-tracking study, mice received either parental
      DCs or DC/NF cells in the left or right footpad, respectively, and combined I-124
      PET/CT and bioluminescence imaging (BLI) were performed. In vivo PET/CT imaging
      with I-124 revealed higher activity of the radiotracer in the draining popliteal
      lymph nodes (DPLN) of the DC/NF injection site at day 1 than DC injection site (p
      < 0.05). The uptake value further increased at day 4 (p < 0.005). BLI also
      demonstrated migration of DC/NF cells to the DPLNs at day 1 post-injection, and
      signals at the DPLNs were much higher at day 4. These data support the
      feasibility of hNIS reporter gene imaging in the tracking of DC migration to
      lymphoid organs in living mice. DCs expressing the NIS reporter gene could be a
      useful tool to optimize various strategies of cell-based immunotherapy. 

PMID- 25974753
TI  - Influence of Helical Structure on Chiral Recognition of Poly(phenylacetylene)s
      Bearing Phenylcarbamate Residues of L-Phenylglycinol and Amide Linage as
      Pendants.
AB  - Four poly(phenylacetylene)s (PPA-1~4) bearing phenylcarbamate residues of L
      phenylglycinol and amide linkage as pendants were prepared to be used as chiral
      stationary phases (CSPs) for high-performance liquid chromatography (HPLC), and
      the influences of coating solvents, dimethylformamide (DMF) and tetrahydrofuran
      (THF), which were used for coating the polymers on silica gel, on the helical
      structure of the polymers and their chiral recognition abilities were
      investigated. The structure analysis of PPA-1~4 by (1) H nuclear magnetic
      resonance (NMR), size exclusion chromatography (SEC), optical rotation, and
      circular dichroism (CD) spectra indicated that the polymers possess the cis
      transoidal structure with dynamic helical conformation. The polymers in THF seem
      to have shorter conjugated helical main chains along with a tighter twist
      conformation than those in DMF. The chiral recognition abilities of PPA-1~4 with
      the different helical structures induced by the coating solvents were evaluated
      as the CSPs in HPLC. The helical structures of PPA-1~4 induced with THF are
      preferable for chiral recognition for some racemates compared to those induced
      with DMF, and higher chiral recognition abilities of PPA-1~ were achieved using
      THF.

PMID- 25974755
TI  - Caffeine enhances and accelerates the expression of sensitization induced by coca
      paste indicating its relevance as a main adulterant.
AB  - BACKGROUND AND OBJECTIVES: Caffeine is an active adulterant found in several
      drugs of abuse including coca paste (CP). We had previously demonstrated that
      caffeine potentiated the acute stimulant effect induced by CP seized samples. The
      role of caffeine in the expression of sensitization elicited by a CP seized
      sample (CP1) was here evaluated. METHODS: CP1 (equivalent dose of 10 mg/kg of
      cocaine), cocaine (pure, 10 mg/kg), a combination of cocaine 10 mg/kg plus
      caffeine 2.5 mg/kg (CP1-surrogate) and saline (control) were intraperitoneally
      injected in male rats under two different sensitization schedules. Ambulatory
      locomotion was recorded in 58 animals. RESULTS: After five daily CP1 injections
      and 5 days of withdrawal, CP1-challenged animals displayed a more robust
      sensitization than cocaine-treated animals. When a 3 injections-regime of CP1
      surrogate or cocaine was assayed, only CP1-surrogate was able to elicit
      sensitization. DISCUSSION AND CONCLUSIONS: Caffeine enhances and accelerates the
      CP1-induced sensitization. SCIENTIFIC SIGNIFICANCE: Results may shed light on the
      fast and high dependence observed in CP users.

PMID- 25974756
TI  - Modified Fontan Conversion: An Alternative Technique for Adult Patients.
AB  - A need persists for Fontan conversion that provides alternative approaches for
      the individual anatomical challenges occurring in these unusual and complex adult
      patients. The pulmonary arteries present unique variations and the surgical
      technique needs to be intraoperatively addressed. We describe a technique for
      Fontan conversion for performing the distal anastomosis of the extracardiac
      conduit, allowing adequate matching to the pulmonary arteries and preserving an
      optimal flow into the Fontan circuit.

PMID- 25974754
TI  - Emerging Targets for Therapeutic Development in Diabetes and Its Complications:
      The RAGE Signaling Pathway.
AB  - Types 1 and 2 diabetes are on the rise worldwide. Although the treatment of
      hyperglycemia has benefited from recent advances, aggressive efforts to maintain
      euglycemia may be fraught with risk, especially in older subjects or in subjects
      vulnerable to hypoglycemic unawareness. Hence, strategies to prevent and treat
      the complications of hyperglycemia are essential. In this review we summarize
      recent updates on the biology of the receptor for advanced glycation endproducts
      (RAGE) in the pathogenesis of both micro- and macrovascular complications of
      diabetes, insights from the study of mouse models of obesity and diabetic
      complications, and from associative studies in human subjects. The study of the
      mechanisms and consequences of the interaction of the RAGE cytoplasmic domain
      with the formin, mDia1, in RAGE signal transduction, will be discussed. Lastly,
      we review the "state-of-the-art" on RAGE-directed therapeutics. Tackling
      RAGE/mDia1 may identify a novel class of therapeutics preventing diabetes and its
      complications. 

PMID- 25974757
TI  - Treatment Factors Associated With Survival in Early-Stage Oral Cavity Cancer:
      Analysis of 6830 Cases From the National Cancer Data Base.
AB  - IMPORTANCE: Most patients with oral cavity squamous cell cancer (OCSCC) are
      initially seen at an early stage (I and II). Although patient and tumor
      prognostic features have been analyzed extensively, population-level data
      examining how variations in treatment factors impact survival are lacking to
      date. OBJECTIVE: To analyze associations between treatment variables and survival
      in stages I and II oral cavity squamous cell carcinoma. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective study of cases in the National Cancer Data Base.
      Patients diagnosed as having stage I or II OCSCC between January 1, 2003, and
      December 31, 2006, and treated with surgery were identified. Univariate and
      multivariable analyses of overall survival based on patient, disease, and
      treatment characteristics were conducted. MAIN OUTCOMES AND MEASURES: Overall
      survival and survival at 5 years. RESULTS: In total, 6830 patients were included.
      Survival at 5 years was 69.7% (4760 patients). On univariate analysis, treatment
      factors associated with improved survival included treatment at academic or
      research institutions, no radiation therapy, no chemotherapy, and negative
      margins (P < .001 for all). Neck dissection was associated with improved survival
      (P = .001), reflecting pathologic restaging and elimination of patients with
      occult nodal disease. Patients treated at academic or research institutions were
      more likely to receive neck dissection and less likely to receive radiation
      therapy or have positive margins. On multivariable analysis, neck dissection
      (hazard ratio [HR], 0.85; 95% CI, 0.76-0.94; P = .003) and treatment at academic
      or research institutions (HR, 0.88; 95% CI, 1.01-1.26; P = .03) were associated
      with improved survival, whereas positive margins (HR, 1.27; 95% CI, 1.08-1.49; P
      = .005), insurance through Medicare (HR, 1.45; 95% CI, 1.25-1.69; P < .001) or
      Medicaid (HR, 1.96; 95% CI, 1.60-2.39; P < .001), and adjuvant radiation therapy
      (HR, 1.31; 95% CI, 1.16-1.49; P < .001) or adjuvant chemotherapy (HR, 1.34; 95%
      CI, 1.03-1.75; P = .03) were associated with compromised survival. CONCLUSIONS
      AND RELEVANCE: Prognostic impacts of treatment factors in early OCSCC are
      presented. Overall survival for early OCSCC varies with demographic and tumor
      characteristics but also varies with treatment and system factors, which may
      represent targets for improving outcomes in this disease.

PMID- 25974760
TI  - Client-centred ADL intervention after stroke: Significant others' experiences.
AB  - BACKGROUND: Client-centredness is a prominent contemporary concept in
      rehabilitation. However, there is a lack of knowledge on if and how a client
      centred rehabilitation approach is incorporated in the everyday life of
      significant others of people who receive such rehabilitation. OBJECTIVE: Explore
      and describe if and how a client-centred ADL intervention (CADL) was integrated
      in the everyday lives of significant others of people with stroke. MATERIALS AND
      METHODS: Qualitative longitudinal design, with a grounded theory approach. Seven
      significant others, who cohabited with persons receiving a CADL intervention,
      were interviewed during the first year. FINDINGS: One core category was
      identified: "Taking responsibility and achieving balance with respect to self
      esteem in order to get on with everyday life". The integration of the CADL was a
      process. A key aspect was that as the person with stroke acted upon his/her own
      desired activity goals the significant others were encouraged to act on their own
      needs. CONCLUSIONS: Enablement is important also for the significant others of
      people with stroke. One way of enabling significant others to maintain an active
      lifestyle and find respite in everyday life might be to enable people with stroke
      to formulate and act upon their desired activity goals.

PMID- 25974759
TI  - Rotation of Boar Semen Doses During Storage Affects Sperm Quality.
AB  - It is common practice to rotate boar semen doses during storage for prevention of
      sperm sedimentation. In this study, the effect of rotation of boar semen doses
      during storage on sperm quality was investigated. Manual turning twice daily and
      automatic rotation five times per hour resulted in the following effects:
      alkalinization of the BTS-extender, loss of membrane integrity at day 3, and loss
      of motility and changes in sperm kinematics during a thermoresistance test at day
      5. Using a pH-stabilized variant of BTS extender, sperm motility and velocity
      decreased in continuously rotated samples, whereas membrane integrity and
      mitochondrial activity remain unaffected. It is concluded that rotation of semen
      samples adversely affects sperm quality and, therefore, should no longer be
      recommended for AI practice. 

PMID- 25974758
TI  - Forecasting the 2013-2014 influenza season using Wikipedia.
AB  - Infectious diseases are one of the leading causes of morbidity and mortality
      around the world; thus, forecasting their impact is crucial for planning an
      effective response strategy. According to the Centers for Disease Control and
      Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and
      causes major economic impacts resulting from hospitalization and absenteeism.
      Understanding influenza dynamics and forecasting its impact is fundamental for
      developing prevention and mitigation strategies. We combine modern data
      assimilation methods with Wikipedia access logs and CDC influenza-like illness
      (ILI) reports to create a weekly forecast for seasonal influenza. The methods are
      applied to the 2013-2014 influenza season but are sufficiently general to
      forecast any disease outbreak, given incidence or case count data. We adjust the
      initialization and parametrization of a disease model and show that this allows
      us to determine systematic model bias. In addition, we provide a way to determine
      where the model diverges from observation and evaluate forecast accuracy.
      Wikipedia article access logs are shown to be highly correlated with historical
      ILI records and allow for accurate prediction of ILI data several weeks before it
      becomes available. The results show that prior to the peak of the flu season, our
      forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI
      observations that contained the actual observations for most weeks in the
      forecast. However, since our model does not account for re-infection or multiple
      strains of influenza, the tail of the epidemic is not predicted well after the
      peak of flu season has passed. 

PMID- 25974761
TI  - Breast health and reducing breast cancer risk: a functional medicine approach.
AB  - BACKGROUND/OBJECTIVE: A functional medicine approach to reduce breast cancer risk
      is preferable to early detection and treatment in maintaining breast health.
      Estrogens are implicated in breast cancer initiation through conversion to
      metabolites that react with DNA to form specific adducts associated with the
      development of breast cancer. The purpose of this study was to determine the
      ability of a defined clinical intervention, the AVERTi-Healthy Breast Program
      (AHBP), to reduce breast cancer risk conditions likely to develop into breast
      disease. METHODS: To obtain evidence that risk conditions in breast tissue can be
      reduced with a defined, multifaceted approach, this small clinical trial of 21
      women measured indicators of breast health. A detailed clinical evaluation was
      conducted with all participants, including identification of physical symptoms,
      such as areas of tenderness upon palpation. Two laboratory assessments were
      conducted to determine the efficacy of the AHBP. First, 31 estrogen metabolites,
      estrogen conjugates, and depurinating estrogen-DNA adducts in urine samples taken
      before intervention were analyzed. The ratio of DNA adducts to metabolites and
      conjugates was calculated for each sample. Second, oxidative stress was analyzed
      by measuring the redox potential of glutathione and cysteine in blood plasma. All
      assessments were conducted before and after participation. RESULTS: The estrogen
      adduct ratio and redox potential were improved after 90 days on the AHBP. A
      significant mean reduction of 3.31 (p=0.03) was observed in the adduct ratio,
      along with a significant improvement in the redox potential of 3.80 (p=0.05). The
      significant change in the adduct ratio occurred in women whose oxidative stress
      profile also improved. CONCLUSION: These significant within-individual decreases
      suggest that the AHBP can reduce the risk for breast cancer in a relatively short
      time.

PMID- 25974763
TI  - The master innovator of the last century.

PMID- 25974764
TI  - The Use of Brainlab Navigation in Le Fort III Osteotomy.
AB  - Le Fort III osteotomy is commonly used in the surgical correction of midface
      hypoplasia, specifically in patients with syndromic craniosynostosis. These
      osteotomies can be associated with significant complications, which are often the
      result of incomplete or inaccurate osteotomies. Brainlab, a technology first
      developed for neurosurgery, has been applied to numerous surgical subspecialties.
      The aim of this study was to report our initial experience using the Brainlab
      VectorVision2 and Brainlab Curve (Brainlab, Westchester, IL) as an intraoperative
      guidance system for osteotomy placement during Le Fort III advancement. Three
      pediatric patients with syndromic craniosynostosis and midface hypoplasia
      scheduled to undergo Le Fort III advancement were scanned preoperatively with 0.6
      mm computed tomography cuts, which were then uploaded to the Brainlab system. All
      surgeries commenced with rigid fixation of the Brainlab registration device to
      the patient's skull. The navigation system was used intraoperatively to
      accurately determine osteotomy sites and trajectories. External distractors were
      placed without complication. Mean length of surgery was 331 minutes, and mean
      estimated blood loss was 500 mL. No transfusion was required with a mean
      postoperative hemoglobin of 8.3 g/dL. The application of Brainlab technology to
      Le Fort III advancement proved useful in establishing precise osteotomy lines and
      trajectories. Looking forward, this technology could be applied to a minimal
      dissection technique in order to avoid extensive blood loss. Further study would
      be needed to determine possible benefits such as reduced complications or
      operative time when using an intraoperative navigation system for image-guided
      osteotomy placement during Le Fort III advancement.

PMID- 25974765
TI  - The "beauty arch: " a new aesthetic analysis for malar augmentation planning.
AB  - Midface is a critical area for the aesthetics of the face. Despite malar
      hypoplasia is often combined with a class III malocclusion, there are few studies
      focusing on the results of a combined approach of malar implants and Le Fort I.
      We describe a new aesthetic analysis, named "beauty arch" analysis, for the
      assessment of sagittal projection of the malar region. We took a reference group
      of 74 Italian women participating in a national beauty contest in 2011 on which
      we performed our analysis. We used the ideal values to elaborate the surgical
      treatment planning of a second group of 45 consecutive female patients affected
      by skeletal class III malocclusion.Twenty-three patients undergo simultaneous Le
      Fort I osteotomy and malar implants. From the descriptive statistical comparison
      of the patients' values before and after orthognathic surgery and malar implants
      with the reference values, we observed how all parameters considered got closer
      to the ideal population. We consider our beauty arch a useful help for surgeon in
      the treatment planning of patients with skeletal malocclusions and malar
      implants.

PMID- 25974766
TI  - Analysis of symptoms according to areas of orbital floor in orbital inferior wall
      fractures.
AB  - OBJECTIVES: A considerable number of patients experiencing facial trauma are
      diagnosed with blowout fracture. Preoperative computed tomographic scan is often
      different from the actual surgical area. This study is restricted to orbital
      floor fracture. This study is expected to help speculating fracture site and
      making surgical plans according to symptoms of periorbital trauma. METHODS: From
      March 2005 to September 2013, a total of 150 cases of orbital floor fracture
      surgeries have been analyzed. This study analyzed the preoperative symptoms at
      the certain fractured area of orbital floor, at the aspects of sagittal view of
      computed tomography, which is sectioned into anterior one-third, middle one
      third, posterior one-third, and mixed types. Symptoms for analysis are diplopia,
      extraocular movement limitation, enophthalmos and other combined facial bone
      fractures, and the like. RESULTS: Fracture areas of orbital floor are 21 cases
      (14%) of anterior one-third, 47 cases (31%) of middle one-third, 7 cases (5%) of
      posterior one-third, and 75 cases (50%) of the mixed. Frequency of diplopia was 0
      case, 24 cases (42.1%), 4 cases (7.0%), and 29 cases (50.9%), respectively. In
      the case of extraocular movement limitation, 0 case, 15 cases (39.5%), 2 cases
      (5.3%), and 21 cases (55.2%) were found, respectively. In the case of
      enophthalmos, 0 case, 5 cases (16.7%), 7 cases (23.3%), and 18 cases (60.0%) were
      found, respectively. The most commonly associated other facial bone fractures
      were nasal bone fractures. CONCLUSIONS: In the case of blowout fracture,
      diplopia, extraocular movement limitation, enophthalmos, and other symptoms are
      checked through physical examination. This study would help speculating fracture
      site and making surgical plans according to symptoms of periorbital trauma.

PMID- 25974767
TI  - Three-dimensional airways reconstruction in syndromic pedriatric patients
      following mandibular distraction osteogenesis.
AB  - BACKGROUND: Airway obstruction, associated with mandibular hypoplasia, is a
      frequent complication in syndromic pediatric patients. The clinical signs of
      airway obstruction change from mild positional obstruction to severe respiratory
      distress with cyanosis. The young age of the patients makes medical management
      extremely complex. METHODS: The purpose was to evaluate the success of surgery,
      evaluating the expansion of the respiratory volumes measured by computer
      tomography analyzed through a software (SimPlant Pro 15). Twelve patients with
      mandibular hypoplasia and respiratory distress were treated between December 2010
      and December 2013. Eleven of them had tracheostomy in the preoperative period.
      The goal of surgery was to prevent permanent tracheostomy or to remove it, if
      present. RESULTS: Volume and surface area increased by an average of 279.2% and
      89.4%, respectively. Tracheostomy was avoided in 1 patient who underwent surgery
      precociously, and it was removed in 10 patients. Only 1 case failed in volume
      airway augmentation, and tracheostomy was not removed. CONCLUSIONS: Computer
      tomography can calculate the cross-sectional areas of the airway in 3 planes of
      space: coronal, sagittal, and axial. In most patients, changes in airways have
      been accompanied by improvements in sleep and breathing, allowing for the removal
      of tracheostomy with an improved quality of life. Three-dimensional
      reconstruction of airways revealed a useful tool to better understand the success
      of surgery. LEVEL OF EVIDENCE: IV.

PMID- 25974768
TI  - Facial twist (asymmetry) in isolated unilateral coronal synostosis: does
      premature facial suture fusion play a role?
AB  - BACKGROUND: Unilateral coronal synostosis (UCS) often causes notable facial twist
      in affected patients. This condition occurs when the midface deviates toward the
      synostotic side, and the lower face deviates away from the synostotic side. The
      exact underlying mechanism for this phenomenon remains unclear. It has been
      proposed that premature fusion of facial sutures may play a role in the formation
      of facial twist. The purpose of this study was to determine whether asymmetrical
      facial suture fusion is present in patients with UCS. METHODS: A single-center
      retrospective study was designed. Our study group consisted of 23 patients with a
      confirmed diagnosis of isolated UCS. Our control group consisted of 17 age
      matched patients with deformational plagiocephaly and 11 normocephalic control
      subjects. The computed tomography scans of the faces were examined for the
      presence of facial suture fusions on both synostotic and nonsynostotic sides. All
      results with P < 0.05 were considered statistically significant. RESULTS: We
      found an increased incidence of fusion of the frontomaxillary, nasofrontal, and
      nasomaxillary sutures on the side of synostosis in UCS when compared with the
      nonsynostotic side and when compared with patients with deformational
      plagiocephaly or normocephalic patients. CONCLUSIONS: Asymmetrical premature
      fusion of facial sutures can potentially be contributing to the facial twist that
      is seen in patients with UCS.

PMID- 25974769
TI  - A computational model of velopharyngeal closure for simulating cleft palate
      repair.
AB  - The levator veli palatini (LVP) muscle has long been recognized as the muscle
      that contributes most to velopharyngeal (VP) closure and is therefore of
      principal importance for restoring normal speech in patients with a cleft palate.
      Different surgical reconstructive procedures can utilize varying degrees of LVP
      overlap, and this study developed a new finite-element model of VP closure
      designed to understand the biomechanical effects of LVP overlap. A three
      dimensional finite-element model was created from adult anatomical dimensions and
      parameters taken from the literature. Velopharyngeal function was simulated and
      compared with experimental measurements of VP closure force from a previous
      study. Varying degrees of overlap and separation of the LVP were simulated, and
      the corresponding closure force was calculated. The computational model compares
      favorably with the experimental measurements of closure force from the
      literature. Furthermore, the model predicts that there is an optimal level of
      overlap that maximizes the potential for the LVP to generate closure force. The
      model predicts that achieving optimal overlap can increase closure force up to
      roughly 100% when compared with too little or too much overlap. The results of
      using this new model of VP closure suggest that optimizing LVP overlap may
      produce improved surgical outcomes due to the intrinsic properties of muscle.
      Future work will compare these model predictions with clinical observations and
      provide further insights into optimal cleft palate repair and other craniofacial
      surgeries. 

PMID- 25974770
TI  - Craniofacial reconstruction using patient-specific implants polyether ether
      ketone with computer-assisted planning.
AB  - Reconstruction of bony craniofacial defects requires precise understanding of the
      anatomic relationships. The ideal reconstructive technique should be fast as well
      as economical, with minimal donor-site morbidity, and provide a lasting and
      aesthetically pleasing result. There are some circumstances in which a patient's
      own tissue is not sufficient to reconstruct defects. The development of
      sophisticated software has facilitated the manufacturing of patient-specific
      implants (PSIs). The aim of this study was to analyze the utility of polyether
      ether ketone (PEEK) PSIs for craniofacial reconstruction. We performed a
      retrospective chart review from July 2009 to July 2013 in patients who underwent
      craniofacial reconstruction using PEEK-PSIs using a virtual process based on
      computer-aided design and computer-aided manufacturing. A total of 6 patients
      were identified. The mean age was 46 years (16-68 y). Operative indications
      included cancer (n = 4), congenital deformities (n = 1), and infection (n = 1).
      The mean surgical time was 3.7 hours and the mean hospital stay was 1.5 days. The
      mean surface area of the defect was 93.4 +/- 43.26 cm(2), the mean implant cost
      was $8493 +/- $837.95, and the mean time required to manufacture the implants was
      2 weeks. No major or minor complications were seen during the 4-year follow-up.
      We found PEEK implants to be useful in the reconstruction of complex calvarial
      defects, demonstrating a low complication rate, good outcomes, and high patient
      satisfaction in this small series of patients. Polyether ether ketone implants
      show promising potential and warrant further study to better establish the role
      of this technology in cranial reconstruction.

PMID- 25974771
TI  - Interrami intraoral fixation technique utilized as a conservative approach to
      edentulous/atrophic mandibular fractures.
AB  - Interrami intraoral Kirschner wire fixation (IRIF) technique is presented as new
      conservative successful indirect rigid fixation utilized for the reduction and
      fixation of edentulous/atrophic mandible fractures. This technique is carried out
      under local anesthesia without the need for open reduction internal fixation,
      which can lead to a compromise in the blood supply of fracture region. It is also
      quicker, easier, requires fewer postoperative visits, and cheaper than small or
      large bone plate fixations.Five edentulous mandibular fractures, 2 of them
      atrophic, 2 non-atrophic, and 1 partial edentulous, were successfully treated. In
      all cases, the IRIF technique was utilized to establish an indirect rigid
      fixation using horseshoe-shaped Kirschner wire with a 2-mm diameter. No
      complication was reported during these cases. This technique prevails over the
      Gunning splint and external edentulous fracture fixation techniques as it
      provides adequate fracture site stability, is more comfortable, and is better
      tolerated for a longer period of time by the patient. In addition, there are
      fewer complications caused by malunions from direct intraoral or extraoral small
      and large plate fixation techniques. Other advantages of the IRIF technique are
      that it enables the mandible to function as a single unit and preserves its
      function and anatomical position immediately after surgery. In contrast, the
      Gunning splint acts only to preserve the balance of a single segment's position.

PMID- 25974772
TI  - Salt as a new colored solid model for simulation surgery.
AB  - BACKGROUND: Simulated craniomaxillofacial surgery is critical for planning the
      procedure, shortening operative time, and practicing the procedure. However,
      typical models are expensive, given their solid materials, and the surgical
      sensations do not accurately reflect the procedure performed using human bone. To
      solve these problems, a new solid salt model has been developed. METHOD:
      Stereolithography data was generated using computed tomography data, and a salt
      model was created using a 3D inkjet printer. By extracting specific data for
      elements such as the teeth and mandibular canal, these elements were highlighted
      in the solid model using different colored material. Also, we compared the
      maximum load and plastic deformation of the salt model, a stereolithographic
      resin model, and a pig limb. RESULT: The salt model had similar tenacity to bone,
      and the risk of damage to the teeth and inferior alveolar nerve was easily
      confirmed. CONCLUSION: The material cost of the salt model is extremely low, and
      the salt model may provide a more accurate sensation of cutting human bone. Thus,
      this model is useful for both simulated operation and practice for inexperienced
      surgeons.

PMID- 25974773
TI  - Cleft lip nose correction combining open rhinoplasty with the Dibbel technique.
AB  - Cleft lip nose rhinoplasty is a challenging procedure because of the different
      presentation and severity of the deformity. Due to this presentation type, there
      is still no standard procedure correcting all the components of the deformity
      although a number of techniques have been published in literature. In this study,
      the effectiveness of the combination of open rhinoplasty and the Dibbel technique
      with nasal sill augmentation was evaluated. We hereby report our experience with
      7 patients who had unilateral cleft lip nose deformity with slumped lower lateral
      cartilage and underprojected and deformed dome, operated on between September
      2010 and April 2013 by 1 surgeon. The mean age of the patients at the time of
      surgery was 24.5 years (18-38 years) and the patients were followed up for an
      average of 18.5 months (6-31 months). All patients were operated on with open
      rhinoplasty and Dibbel technique combination with nasal sill augmentation.
      Frontal, lateral, oblique, and basilar photographs were obtained preoperatively
      and postoperatively for each patient. Nasal projection, columella height,
      nasolabial angle, nasal sill symmetry, and base width were measured on the
      photographs for comparison of preoperative and postoperative results. All
      patients' medial and lateral cantus distances were used for photographic
      standardization. The results demonstrated that there was a statistically
      significant increase in nasal projection (2.13 +/- 0.28 mm preoperatively versus
      2.31 +/- 0.08 mm postoperatively; P = 0.018), columella height (1.07 +/- 0.25 mm
      preoperatively versus 1.21 +/- 0.18 mm postoperatively; P = 0.028), nostril apex
      height (1.11 +/- 0.15 mm preoperatively versus 1.22 +/- 0.11 mm postoperatively,
      P < 0.028), nasolabial angle (77.71 +/- 8.74 mm preoperatively versus 91.33 +/-
      6.49 mm postoperatively; P < 0.05), and nasal sill symmetry (0.42 +/- 0.15 mm
      preoperatively versus 0.27 +/- 0.07 mm postoperatively; P < 0.05), and a
      significant decrease of alar width (2.35 +/- 0.44 mm versus 2.16 +/- 0.32 mm
      postoperatively; P = 0.018) on the affected side in response to surgery. The
      results of this study demonstrated that the Dibbel technique and open rhinoplasty
      combination with nasal sill augmentation is an effective and safe method for the
      correction of cleft lip nose deformity in respect to nasal symmetry.

PMID- 25974774
TI  - The effect of cleft maxillary distraction osteogenesis on the levator veli
      palatini and velopharyngeal function.
AB  - BACKGROUND: Le Fort I maxillary distraction with the rigid external distraction
      (RED) device is performed to correct severe midface retrusion in cleft patients,
      but it may adversely affect velopharyngeal function. OBJECTIVES: This study aims
      to investigate the angular changes in the levator veli palatini (LVP) and its
      influence on velopharyngeal function after maxillary distraction using 3
      dimensional computed tomography (3D CT) scan volume rendered images. METHODS:
      This was a retrospective study of 12 patients. Group 1 had no velopharyngeal
      function deterioration and group 2 had velopharyngeal function deterioration.
      Preoperative and 1 year postoperative CT scans were analyzed with Mimics v10
      software. Segmentation of the LVP and the nasopharyngeal airway was performed and
      volumetric images were obtained. Six measurements were made: (1) the angle
      between the levator plane and the Frankfort horizontal, (2) the angle between the
      levator plane and the soft palate plane, (3) the angle between the 2 LVP muscles,
      (4) the pharyngeal depth, and (5, 6) the movement of the inferior pharyngeal
      point with respect to the horizontal and vertical planes. The independent samples
      t test, Mann-Whitney test, and paired t tests were used for statistical analyses
      (P < 0.05). RESULTS: Group 2 had statistically significant reduction in the angle
      between the levator plane and Frankfort horizontal as well as the soft palate
      plane. Group 1 had a statistically significant increase in the pharyngeal depth
      and movement of the inferior pharyngeal point with respect to the horizontal
      plane. CONCLUSION: A decrease in the angle between the levator plane and the
      Frankfort horizontal or the soft palate plane was associated with velopharyngeal
      function deterioration.

PMID- 25974775
TI  - Late oropharyngeal functional outcomes of suicidal maxillofacial gunshot wounds.
AB  - PURPOSE: The aim of this study was to evaluate the long-term aesthetic and
      functional results of suicidal gunshot injuries using objective methods to
      identify the residual problems after one-stage reconstruction. METHODS: Twenty
      male patients with gunshot injuries resulting from suicide attempts who were
      treated in the Department of Plastic and Reconstructive Surgery at Gulhane
      Military Medical Academy were included in the study. The control group was
      composed of 10 male volunteers. The reconstructions of all involved structures
      were performed within 1-3 days of the injury. The patients were evaluated both
      aesthetically and functionally. The Body Satisfaction Scale was used for
      evaluation of aesthetic appearances of the facial structures. To evaluate
      swallowing, videofluoroscopy, cine-magnetic resonance imaging, submental
      electromyography, Functional Endoscopic Evaluation of Swallowing, and submental
      ultrasound were performed. Perceptual speech analysis was used for speech
      evaluation. RESULTS: The Body Satisfaction Scale score was statistically higher
      in the control group than in patients with both ongoing and completed
      reconstructions (P < 0.05). Swallowing disturbances and their frequencies were
      higher in the study group than in the control group. The most frequently observed
      swallowing disturbance was stasis in the sinuses. The laryngeal elevation and
      geometric angle of the epiglottis in the study group were statistically lower
      than in the control group (P < 0.05). The mean amplitude of contraction of
      submental muscles was lower in the study group than in the control group (P <
      0.05). The Multidimensional Voice Program showed statistically significant
      differences between the treatment and control groups (P < 0.01). CONCLUSION:
      Objective assessment methods enabled us to retrospectively evaluate the treatment
      and identify the specific problem underlying functional and aesthetic
      morbidities.

PMID- 25974776
TI  - Occurrence of maxillary sinus membrane perforation following nasal suction
      technique and ultrasonic approach versus conventional technique with rotary
      instruments.
AB  - The authors compared the efficacy of 2 different techniques for sinus membrane
      elevation for maxillary lining lifted using a lateral window approach: nasal
      suction technique and ultrasonic surgery approach versus traditional approach.
      Thirty partially edentulous patients, having bilaterally 1 to 5 mm of residual
      bone height and at least 5 mm bone width below the maxillary sinuses as measured
      on computed tomography scans, were randomized to receive two 2-stage sinus lift
      procedures using the lateral window approach. On one side, the sinus lining the
      membrane was elevated with nasal suction technique and ultrasonic surgery
      approach, whereas on the contralateral side the membrane was elevated after
      osteotomy prepared using a round oral surgery bur. No patient dropped out. Four
      small perforations of membrane (<5 mm) were observed in group 1 (control) but not
      in group 2 (test). A statistically significant difference was present between the
      incidence of sinus membrane perforation in group 1 versus 2 (control versus test)
      (P < 0.01). In conclusion, the sinus lift with ultrasonic surgery and nasal
      suction technique was used to prevent a perforation of sinus membrane.

PMID- 25974777
TI  - Temporomandibular joint disorders treated with articular injection: the
      effectiveness of plasma rich in growth factors-Endoret.
AB  - The objective of this study was to evaluate the effectiveness of the
      temporomandibular joint (TMJ) osteoarthritis treatment through articular
      injections of plasma rich in growth factors (PGRF)-Endoret. Thirteen patients
      (median age, 47.64 y; SD, 7.51; range, 40-64 y; male-female ratio, 2:11) with
      osteoarthritis of TMJ associated to chronic pain have been selected. They were
      treated with articular injections of PRGF-Endoret, measuring the maximum mouth
      opening and pain level before the first injection (t0), 30 days after just before
      the second (t1), and after 6 months (t2). Data were analyzed using the paired
      Student's t-test data. The visual analogue scale score at t0 is 7.69 (range, 4
      10; SD, 1.9), whereas that at t1 is 1.54 (range, 0-5; SD, 1.74) and that at t2 is
      0.23 (range, 0-2; SD, 0.65). These differences in the results are statistically
      highly significant (P < 0.0001 comparison t0-t1 and t0-t2 and P < 0.01 comparison
      t1-t2). In terms of maximum mouth opening, it reduced from 30.15 mm at t0 (range,
      26-40 mm; SD, 4.44) to 37.54 mm at t1 (range, 31-51 mm; SD, 5.10), with an
      increase of 7.38 mm (range, 4-11 mm; SD, 2.02) and a highly significant
      difference (P < 0.0001). At t2, it was 39.54 mm (range, 34-51; SD, 4.55) with an
      increase of 9.38 mm (range, 5-12 mm; SD, 2.21) compared with t0 and that of 2.00
      mm compared with t1. Both differences in the results are statistically
      significant (P < 0.0001 and P < 0.01, respectively). The articular injections of
      PRGF-Endoret represent a very efficient method to control pain and to improve the
      TMJ mobility.

PMID- 25974778
TI  - Anatomical and aesthetical reconstruction of complex hair-bearing areas: a three
      step procedure including implant of dermal regeneration templates, skin grafting,
      and hair micrografting.
AB  - Reconstructive surgery of complex hair-bearing skin defects often represents a
      challenge for the plastic surgeon; indeed, a multistage procedure is to be
      planned, including a first reconstructive step including local flaps, even if pre
      expanded, or for larger defects, microsurgical flaps. To date, the implant of
      dermal regeneration templates has been proven an effective alternative. The
      authors relate their results of a complex hair-bearing reconstruction of a scalp
      and brow defect after a friction road burn with those reported in literature,
      concluding that a 3-staged reconstruction (dermal template implantation, skin
      grafting, and finally hair micrografting) can achieve good results in this
      complex kind of reconstruction. Histological specimens taken 2 years later
      confirmed a full anatomical reconstruction of the hair-bearing areas. Finally,
      this paper reports the first case of brow reconstruction performed with these
      techniques. 

PMID- 25974779
TI  - Rehabilitation with 4 zygomatic implants with a new surgical protocol using
      ultrasonic technique.
AB  - When the residual bone crest cannot allow the placement of standard implants, the
      treatment for complete arch rehabilitation of severely atrophic maxillae can be
      performed with 4 zygomatic implants (ZIs) and immediate function with predictable
      results in terms of aesthetics, function, and comfort for the patient. However,
      even if ZIs' rehabilitations showed a good success rate, this surgery is
      difficult and need a skillful operator. Complications in this kind of
      rehabilitation are not uncommon; the main difficulties can be related to the
      reduced surgical visibility and instrument control in a critical anatomic area.
      All the surgical protocols described in the literature used drilling techniques.
      Furthermore, the use of ultrasonic instruments in implant surgery compared with
      drilling instruments have shown advantages in many aspects of surgical
      procedures, tissues management, enhancement of control, surgical visualization,
      and healing. The aim of this study was to report on the preliminary experience
      using ultrasound technique for ZIs surgery in terms of safety and technical
      improvement. Ten consecutive patients with severely atrophic maxilla have been
      treated with 4 ZIs and immediate complete arch acrylic resin provisional
      prostheses. The patients were followed up from 30 to 32 months evaluating implant
      success, prosthetic success, and patient satisfaction with a questionnaire. No
      implants were lost during the study period, with a 100% implant and prosthetic
      success rate. Within the limitations of this preliminary study, these data
      indicate that ultrasonic implant site preparation for ZIs can be a good
      alternative to the drilling technique and an improvement for the surgeon.

PMID- 25974780
TI  - Implant-supported prostheses esthetic outcomes after socket preservation
      technique.
AB  - Bone and soft tissue remodeling after tooth extraction may have dramatic effects.
      The socket preservation technique has demonstrated to be effective in maintaining
      volume before implant placement. The Pink Esthetic Score (PES) is an easy and
      complete evaluation of esthetic parameters. The aim of this study was to compare
      the PES index of anterior teeth needing to be replaced and the correspondent
      implant-supported prostheses after the socket preservation technique with 1 year
      of follow-up. Twenty-four patients were enrolled in this study. Eighteen
      maxillary central incisors and 6 maxillary lateral incisors were extracted, and
      then, every alveolar site was treated with the socket preservation technique and
      filled with Bio-Oss, mixed with fibrin glue, and covered with a collagen sponge.
      After 6 months of undisturbed healing, implants were placed and left healing for
      4 months. After they were regularly loaded and at 1 year of follow-up, peri
      implant PESs were recorded. All implants integrated successfully. No dropouts
      were recorded. Comparing PES results before extraction (mean, 12.25) and after
      implant loading (mean, 12.35), those around implants are similar if not better,
      and there are no statistically significant differences as analyzed with the t
      test. The socket preservation technique combined with delayed implant placement
      and a standard healing time before implant loading has demonstrated to be
      effective in maintaining volumes and also esthetic values around implants
      compared with PES values before tooth extraction. 

PMID- 25974781
TI  - Conservative treatment with plasma rich in growth factors-Endoret for
      osteoradionecrosis.
AB  - OBJECTIVES: Osteoradionecrosis (ORN) is the worst long-term complication due to
      radiotherapy to the head and neck and is defined as an area of exposed necrotic
      oral bone, with failure to heal for at least 3 months. In most cases, ORN is
      associated with oral surgery procedures involving the jaw bone. The aim of this
      study was to evaluate the safety and effectiveness of a biological approach for
      ORN treatment. METHODS: A series of 10 patients with ORN were treated by
      debridement of necrotic bone using an ultrasound device followed by application
      of plasma rich in growth factors (PGRF)-Endoret to improve and accelerate soft
      tissue healing. Patients were followed clinically and radiographically up to 12
      months. Pain was assessed in the first week postsurgery using a visual analogue
      scale (VAS). Maturation and quality of tissue healing was assessed using a
      modified healing index. RESULTS: All cases were successfully treated. No
      intraoperative or postoperative complications occurred. Clinical and radiographic
      evaluations showed no signs of persistent infection or exposed bone up to 12
      months of follow-up. The maturity and quality of the regenerated tissues was
      excellent, surgical wounds always achieving complete closure. VAS scores and
      trismus were very low in all patients, which did not take analgesics since the
      third day after surgery. CONCLUSIONS: PRGF-Endoret is beneficial, as an adjunct
      to surgical treatment of osteoradionecrosis, for predictable enhancement of
      tissue vascularization and epithelialization in patients with a history of head
      and neck radiotherapy.

PMID- 25974782
TI  - Translational value of sheep as animal model to study sinus augmentation.
AB  - Sinus augmentation is a routine surgical procedure in dentistry. At present,
      various animal models are available for the research purpose on this topic. In
      particular, for the first time, we have performed a morphological study on sheep
      sinus, using cone beam computed tomography (CBCT), to precisely define the
      anatomy of the ovine sinus. Then, we compared the sheep and human sinus
      morphological parameters, in order to uniform the research approach to the sinus
      augmentation procedures and to standardize this experimental model. Six fresh
      heads of adult female sheep were studied with CBCT and histologic examination to
      determine the dimensions and the organization of the ovine maxillary sinus. The
      comparison of the dimensional values between man and sheep shows evident
      differences between the two species; CBCT offers detailed information for
      studying normal maxillary sinus. Human and sheep maxillary sinus show anatomical
      differences that must be taken into account in experimental procedures. 

PMID- 25974783
TI  - Morphological Aspect and iNOS and Bax Expression Modification in Bone Tissue
      Around Dental Implants Positioned Using Piezoelectric Bone Surgery Versus
      Conventional Drill Technique.
AB  - BACKGROUND: The aim of this work is to evaluate differences occurring in bone
      tissue around dental implants positioned using piezoelectric or conventional
      drill technique. METHODS: Twenty-four implants were inserted bilaterally in the
      iliac crest of 6 sheep after site preparation through a piezoelectric instrument
      (Test) or after site preparation through conventional drill technique with rotary
      instruments (Control). Animals were randomly divided to be euthanized at 15 and
      30 days post-intervention (p.i.); peri-implant bone samples were withdrawn and
      processed for histological analysis and immunohistochemical evaluation of iNOS
      and Bax expression. RESULTS: Active remodeling phenomena in both Test and Control
      samples are showed at 15 days p.i., while at 30 days p.i., the overall
      organization of the peri-implant bone resembles native bone tissue.
      Immunohistochemical evaluation reveals a statistically significant increase of
      both iNOS and Bax expression at 15 days p.i. compared to samples obtained 30 days
      p.i. and to native bone. At both healing times, a higher but not statistically
      significant iNOS and Bax expression is recorded in samples from Control compared
      to Test Group. CONCLUSION: Even if the insertion protocol does not seem to
      significantly interfere with the long-term healing process, implant site
      preparation through the piezoelectric bone surgery technique may allow a
      reduction of peri-implant bone tissue inflammation and support a more rapid bone
      tissue healing phase.

PMID- 25974784
TI  - Three-dimensional evaluation of upper airway in patients with obstructive sleep
      apnea syndrome during oral appliance therapy.
AB  - Obstructive sleep apnea syndrome (OSAS) represents a frequent and common
      respiratory disease characterized by repeated episodes of complete and/or partial
      obstruction of upper airways during sleep, normally associated with reduction of
      oxygen saturation in blood. The oral appliances (OAs) are considered to be an
      effective treatment modality thanks to the upper airway enlargement. Lateral
      cephalometry has been used for the 2-dimensional evaluation of upper airway form
      with several limits. We obtained an accurate 3-dimensional (3D) volume analyses
      with cone beam computed tomography (CBCT) scans to confirm the effects of OA on
      the upper airway in patients with OSAS. Ten Italian patients with moderate or
      severe OSA (3 males and 7 females, 53.4 +/- 11.3 years of age, and BMI 24.5 +/-
      2.7), who cannot tolerate continuous positive air pressure therapy and rejected a
      surgical approach, were treated with non-adjustable customized OAs and evaluated
      with CBCT and polysomnography. Upper airway form was examined in the presence and
      absence of OA and the volume was measured and compared in 2 different areas.
      Specific planes have been considered to match the data and calculate the benefit
      obtained with therapy. Nine out of ten patients showed an improvement of total
      upper airway volume and an improvement in apnea-hypopnea index. Volume increased
      both in the posterior soft palate region and in the posterior tongue region. In
      the inferior area, we observed greater differences. 3D image reconstruction
      accurately confirmed morphological changes in the upper airway during OA therapy.
      The use of this 3D evaluation is expected to improve the results of OA therapy in
      the future.

PMID- 25974785
TI  - Failure risk estimates after dental implants placement associated with plasma
      rich in growth factor-Endoret in osteoporotic women under bisphosphonate therapy.
AB  - There is disagreement as to whether it is safe to place implants in patients
      under bisphosphonates (BPs) therapy owing to the risk for developing BP-related
      osteonecrosis of the jaws (BRONJ). The American Association of Oral and
      Maxillofacial Surgeons recommends that dental implants should be avoided in
      oncologic patients treated with intravenous BPs. Conversely, for patients
      receiving oral BPs, dental implant placement is not explicitly contraindicated
      even if a cautious approach is suggested. The aim of the current study was to
      assess the risk level as related to adverse events such as implant failure and
      BRONJ in a large cohort of osteoporotic patients submitted to implant placement
      and concomitant application of plasma rich in growth factor (PGRF)-Endoret. The
      clinical charts of 235 middle-aged women under oral BPs therapy for osteoporosis,
      who underwent positioning of 1267 dental implants, were reviewed. The implants
      were always positioned in association with PRGF-Endoret. The outcomes were
      implant failure and BRONJ. A model based on personal risk factors distribution
      was used for risk assessment. Sixteen implants were lost in 16 patients up to 120
      months of follow-up, leading to a survival of 98.7% and 93.2% on an implant basis
      and patient basis, respectively. No cases of BRONJ were reported. In line with
      the current literature, the present data show that the risk for developing BRONJ
      associated to dental implant surgery remains low for patients receiving oral BPs.
      The use of procedures that could enhance and support healing, such as platelet
      concentrates, should be recommended. 

PMID- 25974787
TI  - How does the mandible grow after early high condylectomy?
AB  - The early high condylectomy (HC), removing the overgrowing area of the condyle,
      may be indicated for condylar hyperplasia. However, in young patients, when the
      HC removes the pathological overgrowing tissue the contralateral condyle is still
      growing. May this surgical procedure, in these growing patients, stop the
      operated side growth creating the conditions for an opposite asymmetry? Authors
      investigate the way the operated mandible develops after the early HC, both as a
      symmetry percentage and in an absolute value related to the unaffected side. A
      sample of 8 consecutive growing patients, 1 male and 7 females, referred to the
      Maxillofacial Surgery Department of Parma University for HC were investigated.
      Patients were longitudinally studied with 3 orthopantomographies at: T0
      (diagnosis: mean age, 13 years; range, 11 years 2 months to 13 years 8 months),
      T1 (after surgery: mean age, 15; range, 13-18 years) and T2 (follow-up: mean age,
      18 years; range, 17-20 years). The x-ray is used to study the condyle, ramus, and
      total vertical structures length by Mattila tracing method. The data were
      analyzed by the Student t test and Wilcoxon matched pairs test; P value was set
      at 0.5. The operated side was overcorrected by HC and; during the investigated
      period, its growth decreased from T0 to T1 and restarted from T1 to T2. The whole
      T0-T2 growth of the operated side was not statistically different from the one of
      the healthy side (P < 0.05). These results suggest that the operated side growth
      may continue in a more normal way after condylectomy.

PMID- 25974786
TI  - Autologous fat grafting in facial volumetric restoration.
AB  - The authors reported their surgical experience about structural fat grafting in
      the management of facial volumetric deficit. The purpose of this study was to
      assess the real indications, cosmetic results, complications, and global patient
      satisfaction of the Coleman technique in redefining facial contours in congenital
      and postoperative deformities. A retrospective analysis of 32 patients grafted
      according to Coleman's technique was performed, and the long-term outcomes and
      patient satisfaction were evaluated. The mean postoperative clinical follow-up
      was 14 months. The morphological changes were analyzed by comparing the
      photographic presurgical facial contour and the postoperative correction of soft
      tissue defects. All consecutive cases reported showed a progressive fat
      resorption for 3 months after surgery and its stable integration only after this
      period. Best results were performed in the treatment of genetically determined
      syndromes, such as the Franceschetti and Romberg syndromes. The authors suggest
      this surgical technique also for the treatment of unaesthetic cutaneous abscess
      cavity after incision and drainage. Unsatisfactory outcomes were obtained in the
      treatment of the posttraumatic facial scar, which needed more surgical
      procedures. 

PMID- 25974788
TI  - Assessment of anterior suspended flaps modification for external
      dacryocystorhinostomy.
AB  - AIM: The aim of this study was to evaluate the functional and/or anatomic success
      rate as well as complications of anterior suspended flaps modification for
      external dacryocystorhinostomy (DCR). METHODS: This is a retrospective study that
      included 50 eyes of 47 patients who underwent anterior suspended flap external
      DCR surgery for nasolacrimal duct obstruction. Diagnosis of nasolacrimal duct
      obstruction was made through irrigation of the nasolacrimal drainage system.
      Anterior flaps of lacrimal sac and nasal mucosa, as large as possible, were
      created in all patients. Posterior flaps of lacrimal sac and exposed nasal mucosa
      were excised. After suturing the anterior flaps with two 6-0 Vicryl sutures, the
      third suture was passed through the orbicularis oculi at the subcutaneous level
      on 1 edge of incision, then from the middle of the anterior flaps and the other
      edge of the incision to the suspended anterior flaps. RESULTS: The success rate
      of 50 surgeries was 96%. In 37 eyes, no problems were reported during the surgery
      and the modified external DCR was performed successfully. The success rate of the
      modified external DCR was 100% in those patients. The average operation time was
      34 +/- 8.2 minutes. CONCLUSIONS: These results suggest that anterior suspended
      flap external DCR is a simple, safe technique with a very high success rate and a
      satisfactory surgical time.

PMID- 25974789
TI  - Orthognathic surgery in patients with cleidocranial dysplasia.
AB  - The aim of this study was to report the orthodontic-surgical approach of a 21
      year-old female patient diagnosed with cleidocranial dysplasia. An orthognathic
      surgery was performed in the maxilla and mandible during the same procedure to
      correct an existing dentofacial deformity (class III malocclusion). In addition,
      malar prostheses were used to correct midface deficiency. After surgical
      intervention, orthodontic treatment continued in order to promote stability,
      function, and aesthetics. Cases of cleidocranial dysplasia treated with the
      defined criteria can bring aesthetic and functional benefits to the patient. 

PMID- 25974790
TI  - Overcoming limitations of short scar minimal access cranial suspension facelift
      for enhanced rejuvenation.
AB  - The minimal access cranial suspension lift, a short-scar facelift, has been
      described to correct sagging and laxity of the lower and middle third of the
      face. It does not, however, fully address the neck or the lateral periorbital
      area frequently needing rejuvenation in most patients. Another shortcoming of the
      minimal access cranial suspension lift technique is visible scarring anterior to
      the temporal hairline that usually occurs despite the suggested surgical
      maneuvers consisting in zigzag beveled incisions. We describe modifications of
      the standard subcutaneous musculoaponeurotic system lift technique, increasing
      its indications for full-face and neck rejuvenation (excluding the forehead) and
      improving final aesthetic outcome. 

PMID- 25974791
TI  - Application of drill in otoplasty: a technical modification.
AB  - PURPOSE: Prominent ear is one of the most common congenital deformities in the
      head and neck region. More than 100 techniques have been described for correction
      of prominent ears in literature. Mustarde technique is one of the most widely
      accepted procedures of otoplasty. In our study, we used a surgical method using a
      drill for correction of prominent ears in combination with the Mustarde
      technique. Patients with only lack of antihelical fold were included the study.
      METHODS: Thirty patients were operated on during 2007-2010. The angle of
      prominent ear from the mastoid tip to the tip of the posterior surface of the
      auricle was measured preoperatively and postoperatively (3 months after
      operation) using jib and protractor. Patient satisfaction was evaluated using a
      questionnaire. RESULTS: The angulation of prominent ear was 45.2 +/- 8.6 degrees
      preoperatively. Postoperatively, the angulation was 25.6 +/- 6.3 degrees. The
      difference was statistically significant (P < 0.001). Fifteen patients (50%)
      reported that the operation was very satisfactory, 13 patients (43.4%) reported
      that the operation was satisfactory, and 2 patients (6.6%) reported that the
      operation was not satisfactory cosmetically. CONCLUSION: The described technique
      of otoplasty using a drill to thin the auricular cartilage is a safe and easy-to
      learn procedure. In Mustarde technique, permanent sutures are used to reshape the
      cartilage structure in fixed position. Over time, structural strength elasticity
      of cartilage can weaken the force of sewing forces. Combining the technique with
      permanent sutures, results were satisfactory. This technique can be used to
      recreate the antihelical fold. We will follow the cases long term to further show
      more results.

PMID- 25974792
TI  - The reconstructive challenges and approach to patients with excoriation disorder.
AB  - Many mental and emotional disorders have some variations of physical
      manifestations that are often the first definitive sign of disease. One such
      disorder is excoriation (skin-picking) disorder, also known as dermatillomania,
      acne excoriee, neurotic excoriation, or psychogenic excoriation. First identified
      in the dermatologic literature in 1920, excoriation disorder involves repetitive
      scratching behavior that sometimes accompanies pruritus and is often associated
      with depression, anxiety, and obsessive-compulsive disorder. In the latest
      edition of the Diagnostic and Statistical Manual of Mental Disorders, the
      Diagnostic and Statistical Manual of Mental Disorders fifth edition, excoriation
      or skin-picking disorder is listed as a stand-alone disorder associated with
      obsessive-compulsive disorder. In certain patients, the skin lesions are shallow
      and have adherent crusts that can be mistaken for acne. These lesions, once
      healed, may appear white and partially atrophic. Because these patients often
      initially present to dermatologists or plastic surgeons for their skin conditions
      rather than to psychiatric professionals, it is important to recognize the
      salient diagnostic features and to acknowledge the importance of a
      multidisciplinary approach to patient care and management. We present a case of a
      51-year-old woman with excoriation disorder who required medical management by
      dermatology, neurosurgery, psychiatry, and plastic surgery for a definitive
      surgical treatment. 

PMID- 25974793
TI  - The use of piezosurgery in cranial surgery in children.
AB  - Piezosurgery is an alternative surgical technique, now widely tested, that uses
      ultrasounds for bone cutting. This device uses ultrasounds to section hard
      tissues without harming surrounding soft tissues. The authors analyzed their
      experience in craniomaxillofacial procedures with piezosurgery. A comparison
      between operation timing and complication rates between piezosurgery and
      traditional cutting instruments has been performed. A total of 27 patients were
      examined (15 females and 12 males; average age, of 5.5 months) affected by
      craniosynostosis. The aim of this study was to analyze the advantages and
      disadvantages of piezosurgery in pediatric craniofacial procedures. Piezoelectric
      device in this study has shown being a valid instrument for bone cutting in
      accurate procedures, because it allows performing a more precise and safer
      cutting, without the risk of harming surrounding tissues. 

PMID- 25974794
TI  - Risk assessment for free tissue transfers: is old age a determining factor?
AB  - INTRODUCTION: Free tissue transfers are more often performed in the elderly with
      the increase in geriatric patient population. The aim of this study was to
      investigate the effect of advanced age in reconstructive microsurgery procedures
      and analyze the association of other variables with complications and surgical
      success. PATIENTS AND METHOD: A retrospective review of 70 consecutive free
      tissue transfers between January 2012 and June 2013 was performed. Patients were
      divided into 2 groups: those younger than 60 years and those aged 60 years or
      older. Besides demographics, the American Society of Anesthesiologists (ASA) risk
      score, comorbid conditions, and anatomic locations for surgery (head and neck,
      extremities, trunk), operative time, need for reoperation, intensive care unit
      (ICU) admission and blood transfusion, length of hospital stay, medical and
      surgical complications, as well as partial and total flap loss were noted and
      analyzed. RESULTS: A total of 71.4% of the patients were younger than 60 years (n
      = 50; average, 37.4 y), and 28.6% of the patients were 60 years or older (n = 20;
      average, 67.5 y). None of the other collected data showed significant difference
      between the groups. Although age was not associated with ICU admission, the
      location of the reconstruction site and the operative time were found to have a
      significant correlation with ICU referral. In this series, the operative time
      correlated with medical complications but not with surgical complications. Higher
      ASA scores did have a negative effect on the incidence of medical complications
      (P = 0.028). CONCLUSIONS: This retrospective review demonstrates that age alone
      is not an independent variable for increased risk in microvascular
      reconstruction. However, operative time, ASA risk score, and location of the
      reconstruction site are more associated with the overall success of free tissue
      transfers.

PMID- 25974795
TI  - Facial Filler Grid (FAFI GRID): A New Method of Facial Analysis.
AB  - Despite the expert execution of the most sophisticated techniques, a precise
      descriptive guide of the treated areas to produce clinical records is lacking.
      The aim of our study was to develop a method of facial analysis to get a
      classification of areas that have to be treated for precise records. Our aim was
      to find an easy and original method for positioning and recording facial filler
      quantities and results. METHODS: We studied this method of analysis on 300
      nonsmoker patients aged between 25 and 55 years. It involves the use of vertical
      and horizontal lines to divide the middle lower third into areas. It is this grid
      like framework of perpendicular lines that gives rise to the name selected for
      the method. RESULTS: Postsurgical analysis with FAFI GRID (Facial Filler Grid)
      indicated a satisfactory outcome, and it proved useful for precise records.
      DISCUSSION: FAFI GRID allows us to treat precise facial points that are treated
      in steps: (1) malar, (2) nose, (3) lower third. The method thus provides an easy
      way to position and orient facial fillers in the entire face.

PMID- 25974796
TI  - The comparison between alar cartilage shortening and columellar-septal suture
      techniques in nasal tip rotation.
AB  - BACKGROUND: One of the main operative goals achieved with tip surgery is to reach
      the ideal nasolabial angle. The main purpose of the current study was to compare
      the effects of alar cartilage vertical incision and shortening (ACS) and
      columellar-septal suture (CSS) techniques on the nasolabial angle. METHODS: In
      this retrospective study, 2 groups were examined: the patients in the first group
      were operated on using vertical alar cartilage incision and shortening, and the
      patients in the second group were operated on using columellar-septal cartilage
      suture. Postoperative photographs between the 2 groups were compared with respect
      to nasolabial angle differences. Statistical analysis was done with SPSS version
      20. RESULTS: In the postoperative evaluation, 50% of ACS and 72.5% of CSS groups
      had achieved desired clinical outcomes. Although the efficacy of the CSS group
      was found to be superior to that of the ACS group, there was no statistically
      significant difference between the groups. Greater nasolabial angle was gained
      using the CSS technique; however, the risk for overrotation was higher in the CSS
      group. CONCLUSIONS: Both ACS and CSS techniques provide reliable reconstructive
      option for nasolabial angle modifications. More predictable results were obtained
      with the ACS technique. The CSS technique is a versatile way of nasolabial angle
      alteration, but there is a higher risk for overrotation.

PMID- 25974797
TI  - Mandibular reconstruction with different techniques.
AB  - Traumas, malformative or dysplastic pathologies, atrophy, osteoradionecrosis, and
      benign or malignant neoplasm can cause bone deficits in the mandible. Consequent
      mandibular defects can determine aesthetic and functional problems; therefore,
      being able to perform a good reconstruction is of critical importance.Several
      techniques have been proposed for mandibular reconstruction over the years. In
      this article, we present and discuss the evolution during the time of the methods
      of mandible reconstruction as well as pros and cons of each procedure on the
      basis of experience of 10 years in the maxillofacial department of the Catholic
      University of Sacred Heart of Rome.Free flaps represent the gold standard method
      of reconstruction of large mandibular defects: the fibula bone flap represents
      the best choice for large defects involving the arch and the mandibular ramus,
      whereas the deep circumflex iliac artery represents a valid alternative for
      mandibular defects involving the posterior region.In cases where free flap
      reconstructions are contraindicated, the use of regional pedicle flap combined
      with autologous bone grafts still represents a valid choice. Patients who are not
      deemed suitable for long and demanding surgery can still be treated using
      alloplastic materials in association with regional pedicle flap or, when adjuvant
      radiation therapy is needed, by simple locoregional pedicle flap. Finally, in
      selected cases, the bone transporting technique should be considered as a valid
      alternative to the more "traditional" reconstructive methods because of the
      extraordinary potential and its favorable cost-benefit ratio. 

PMID- 25974798
TI  - Use of self-tapping metal screws for temporary fixation of a resorbable plate
      system in maxillofacial surgery.
AB  - Resorbable plate systems have been used in maxillofacial surgery to obviate the
      need for plate removal. However, resorbable plates and screws are very costly,
      and refixation with additional screws may be necessary when reduction or
      repositioning of the bone segment is inaccurate. Here we report the use of self
      tapping metal screws for temporary fixation of a resorbable plating system in
      maxillofacial surgery to avoid the use of additional screws following inaccurate
      fixation or the reuse of resorbable screws, which may result in loosening. 

PMID- 25974799
TI  - Retrobulbar hemorrhage during or after endonasal or periorbital surgery: what to
      do, when and how to do it.
AB  - Retrobulbar hemorrhage (RBH) is an uncommon complication of endoscopic sinus
      surgery or periorbital surgery consisting in an accumulation of blood within the
      orbit posteriorly to the eyeball. It must be treated within 90-100 minutes to
      avoid irreversible visual loss. The present paper tries to pinpoint the key steps
      in diagnosis and treatment of RBM.On the wake of a new case, the authors review
      and update their clinical experience and propose a step-by-step protocol to
      diagnose and to treat RBH developing under different circumstances: during
      endoscopic sinus surgery, during periorbital surgery, immediately after the
      surgery, in the awakening room, or postoperatively in the ward.A therapeutic
      ladder is proposed that starts with lateral canthotomy and inferior cantholysis
      and progresses to a lower lid transconjunctival incision with retrocaruncular
      extension.Based on our experience, the proposed guidelines are effective in
      diagnosing and treating RBH. They allow to preserve vision and minimize
      reliquates of this rare and dangerous surgical emergency. 

PMID- 25974800
TI  - Unilateral zygomatic hypoplasia correction by L-shaped zygomatic osteotomy with
      natural coral.
AB  - PURPOSE: Zygomatic osteotomy is a common method of zygomatic hypoplasia
      correction. Natural coral is considered to be a good bone substitute. Few studies
      on unilateral zygomatic hypoplasia correction by zygomatic osteotomy with natural
      coral have been reported. This study was performed to evaluate the clinical
      morphological results and surgical outcomes of unilateral zygomatic hypoplasia
      correction by L-shaped zygomatic osteotomy with natural coral. METHODS: From 1996
      to 2012, a total of 42 patients with hypoplastic zygomas treated by L-shaped
      zygomatic osteotomy with natural coral were included in this study. Based on
      facial analysis results and x-ray and CT measurements, the degradation of natural
      coral, new bone formation, and clinical outcomes were observed and recorded.
      RESULTS: All surgical procedures achieved satisfactory results without
      complications. During the stabilization period of about 12 to 15 months, all
      natural coral blocks were completely degraded and replaced by new bone. Good
      mechanical strength and continuity of the new bone and good zygomatic asymmetry
      were achieved in each patient. No recurrence was observed during the follow-up
      period. CONCLUSION: L-shaped zygomatic osteotomy with natural coral is an
      effective method of unilateral zygomatic hypoplasia correction.

PMID- 25974801
TI  - Juvenile nasopharyngeal angiofibroma: comparison between endoscopic and open
      operative approaches.
AB  - BACKGROUND AND AIM: Juvenile nasopharyngeal angiofibroma (JNA) is a rare vascular
      and fibrous tumor that most commonly affects males in prepuberal and adolescent
      age. Traditionally, these tumors have been removed, after selective embolization,
      with the open surgical approach (degloving), but the interest in the endoscopic
      resection, especially for small tumors, has increased in recent years. To present
      our experience of JNA management, comparing the endoscopic approach and
      open/combined approach. MATERIALS AND METHODS: We conducted a retrospective,
      cross-sectional, and descriptive study of 12 young men, ages between 9 and 19
      years (mean: 13), suffering from nasopharyngeal angiofibroma and treated with
      open surgery (N = 6), with endoscopic excision (N = 5) or with combined approach
      (N = 1). We reviewed demographical data, clinical presentation, surgical approach
      as well as time of surgery, of hospitalization, need of blood transfusion during
      surgery, and complications occurred during hospitalization. RESULTS: All JNA
      patients were male. The average age at diagnosis was 13.7 years (range 9-19
      years). Approximately, 8.3% were classified as Onerci I, 41.7% as Onerci II, and
      50.0% as Onerci III. Preoperative embolization was carried out in all patients.
      All patients were submitted to primary surgical resection, and 2 of them required
      intraoperative blood transfusion. The overall recurrence rate was 8.3% and the
      cure rate was 100%. CONCLUSION: This study confirmed that endoscopic approach
      gives excellent results in small and medium dimensions tumors, whereas open
      surgery remains a safe procedure for patients with larger tumors.

PMID- 25974802
TI  - Morphometrical aspect on angular branch of facial artery.
AB  - Anatomic variability and anastomosis of the angular artery of the facial artery
      with the other arteries are important for both anatomists and surgeons. In
      particular, the angular artery is a significant landmark in
      dacryocystorhinostomy. Because of variations on anatomy of the angular artery,
      there are limited numbers of anatomic studies on the flaps of facial region.
      Hence, the aim of the cadaveric study was to evaluate the anatomic features of
      the angular artery in detail to help surgical procedures.The artery was
      represented under *4 loop magnification in 32 sides of 16 formalin-fixed adult
      cadavers. The angular artery's position, diameter, and branch patterns relevant
      to the nose arterial supply were evaluated. The facial artery ended symmetrically
      in 10 (62.5%) of the cadavers. The facial artery was terminated as angular artery
      in all of the cases. The types of the angular artery were as follows: classical
      angular type in 8 cases (25.0%), nasal type in 15 cases (46.9%), alar type in 4
      cases (12.5%), and labial type in 5 cases (15.6%) on the facial halves. We
      studied the topographic anatomic features of the angular artery for increasing
      reliability of the flaps on the region. The angular arterial anatomic details are
      critical and essential for surgical cosmetic and functional results.

PMID- 25974803
TI  - Eyes of beautiful women and femme fatales depicted in Western portraits.
AB  - This study aimed to compare the eyes of beautiful women and femme fatales
      depicted in Western portraits. A total of 37 samples were collected; 19 beautiful
      women and 18 femme fatales. Nine aspects were measured in reference to the
      corneal horizontal diameter. The estimated corneal vertical diameter was
      calculated by a corneal horizontal diameter multiply constant, 1.11.The double
      fold was observed in 89% (17 of 19) of the beautiful women and 83% (15 of 18) of
      the femme fatales. The eye-width ratio was 2.42 (SD, 0.28) in the beautiful women
      and 2.31 (SD, 0.34) in the femme fatales. The eye-height ratio was 0.91 (SD,
      0.18) in the beautiful women and 0.84 (SD, 0.10) in the femme fatales. Eyebrow-to
      upper lid distance was 0.92 (SD, 0.35) in the beautiful women and 0.89 (SD, 0.23)
      in the femme fatales. The interpupillary distance was 5.00 (SD, 0.46) in the
      beautiful women and 5.00 (SD, 0.71) in the femme fatales. The intercanthal
      distance was 2.72 (SD, 0.42) in the beautiful women and 2.78 (SD, 0.73) in the
      femme fatales The outer canthal distance was 7.32 (SD, 0.64) in the beautiful
      women and 7.20 (SD, 1.01) in the femme fatales. The ptosis amount was -0.01 (SD,
      0.18) in the beautiful women and 0.06 (SD, 0.01) in the femme fatales. For the
      above 7 measurements, there were no significant differences between the 2 groups
      (P > 0.05, t test).It is noteworthy that the beautiful women and femme fatales
      have the same interpupillary distance (5.00). Also, the ptosis ratio was almost
      zero in both groups (-0.01 [SD, 0.18] in the beautiful women and 0.06 [SD, 0.01]
      in the femme fatales). The results of this study might be of some reference in
      performing eyelid surgeries especially in brow lifts or canthoplasties.

PMID- 25974804
TI  - Condensed autogenous bone particles: modified technique.

PMID- 25974805
TI  - The effect of adenoidectomy operation made on patients with adenoid hypertrophy
      on cardiovascular risk reduction.

PMID- 25974806
TI  - Prosthetic rehabilitation using short dental implants associated with homogenous
      bone graft.

PMID- 25974807
TI  - Intramural perimasseteric hemangiomas of the inner cheek.

PMID- 25974808
TI  - The effect of septoplasty operation for nasal septum deviation to cardiovascular
      risk reduction.

PMID- 25974809
TI  - A rare cause of horner syndrome: pediatric lipoblastoma of the neck.

PMID- 25974810
TI  - Clinical Oral Findings in Patients With End-stage Renal Disease Receiving
      Hemodialysis.

PMID- 25974812
TI  - Foreign body removal by inferior meatal antrostomy.

PMID- 25974811
TI  - A modification of the posterior auricular flap used for scapha and helix middle
      one-third defects of the auricle.

PMID- 25974813
TI  - Surgical technique for frontal sinus and nasofrontal duct obliteration.

PMID- 25974814
TI  - Anxiety and depression during expecting time for oral cancer treatment.

PMID- 25974815
TI  - Massive ameloblastic fibroma treated with surgical conservative treatment.

PMID- 25974816
TI  - Unusual long-term complication of polyalkylimide hydrogel manifesting as nasal
      septal abscess.
AB  - Bio-Alcamid is a new synthetic polyacrylic hydrogel that contains alkylimide
      amide groups and pyrogen-free water (96%) and has gained widespread use in
      cosmetic and reconstructive practice since being awarded a Conformite European
      certificate in 2001. According to the research on the efficacy and safety of the
      long-acting filler Bio-Alcamid in the early phases of development, Bio-Alcamid is
      nearly nontoxic and nonallergenic and has long in vivo persistence. It has been
      widely used because of its superior durability compared with short-acting
      fillers. Many published studies have examined only early-phase postoperative
      inflammatory responses. More recently, however, complications with delayed onsets
      ranging from several months to several years, such as inflammation and filler
      migration, have been emerging. Given the rapidly increasing application of long
      term fillers, an increased incidence of complications is expected, and increasing
      awareness of its correct use and complication treatments is needed. To address
      this problem, we reviewed the safety of long-acting fillers on the basis of a
      rare case of surgical incision and drainage of a nasal septal abscess that
      developed in a patient 2 years after Bio-Alcamid was injected into the nasal
      region.

PMID- 25974817
TI  - Successful treatment of posttraumatic arteriovenous malformation of the lower
      lip.
AB  - Arteriovenous malformations (AVMs) are most commonly reported in the brain. Head
      and neck AVMs are reported to occur in 0.1% of the general population. On the
      other hand, posttraumatic AVMs are quite rare. Traumatic AVMs are extremely rare
      in the head and neck and are mostly seen in the extremities. The management of
      such lesions may include selective embolization or surgical exploration with
      ligation. A 13-year-old male adolescent visited our hospital for lower lip
      swelling, which developed 5 years ago after a lower lip laceration. The AVM was
      expanded and was graded as stage II. It was fed by the mandibular branch of both
      facial arteries and drained to the posterior facial vein. The radiologic
      intervention department performed an embolization before the operation. The main
      operation was performed 12 days after the embolization. A well-demarcated AVM
      lesion was found in the oral mucosa and was totally excised under general
      anesthesia. The authors easily performed the operation owing to the embolization
      making the AVM definitely demarcated and firmly palpable. The lip closure was
      done carefully considering the lip contour. No sign of recurrence was seen during
      6 months of follow-up. The excellent treatment result of the posttraumatic facial
      AVMs occurs largely because of a collaboration with the radiologic intervention
      department using the selective embolization.

PMID- 25974818
TI  - Nasal septal perforation reconstruction with superior-based pedicled nasolabial
      island flap in a patient with the Raynaud phenomenon.
AB  - Perforation of the nasal septum may have multiple causes, and there are lots of
      options for reconstruction. We discuss a septal perforation case with Raynaud
      phenomenon. 

PMID- 25974819
TI  - Relationship between activity of gluthatione peroxidase and nitric oxide in
      synovial fluid and the progression of temporomandibular joint internal
      derangement.
AB  - The purposes of this study were to measure the activity of glutathione peroxidase
      (GPX) and nitric oxide (NO) in the synovial fluid of patients with
      temporomandibular joint (TMJ) internal derangement (ID) and to indicate the
      relationship between the activity of GPX and NO and the progress of the ID.
      Twenty-six patients with TMJ ID were identified and classified according to
      Wilkes staging through clinical and radiologic examinations. Levels of GPX were
      determined indirectly by a coupled reaction with glutathione reductase. Levels of
      NO were measured colorimetrically. The activity of GPX and NO was observed to be
      progressively increasing as the stage of the TMJ ID progressed. There were
      significant correlations between the 2 substances and the Wilkes stages.
      Oxidative stress may have a role in the pathogenesis of TMJ ID. In synovial
      fluid, GPX and NO activities are increased as the stage of the disease increased.
      Increase in the activities of GPX might not be enough to prevent progression of
      the TMJ ID.

PMID- 25974820
TI  - Dehiscence of the infraorbital canal with the maxillary antral empyema: a new
      cause of facial pain.
AB  - The infraorbital nerve is the largest cutaneous branch of the maxillary divisions
      of the trigeminal nerve. It may produce a bony ridge on the antral roof but
      usually goes through within the maxillary bone as a discrete canal. Rarely, it
      could be partially or completely dehiscent, lying submucosally on the antral roof
      as in this case. We describe a case of longstanding facial pain because of
      dehiscence of the infraorbital canal associated with the maxillary antral
      empyema. Endoscopic sinus surgery was successful in relieving the symptom.

PMID- 25974821
TI  - Congenital laryngomucocele: a rare cause of airway obstruction in a newborn.
AB  - Congenital laryngoceles are defined as cystic dilatation of laryngeal saccules
      and are an extremely rare cause of newborn respiratory distress. A
      laryngomucocele occurs when the neck of the laryngocele gets obstructed and fills
      with the mucoid secretions of the saccule. It may cause stridor, respiratory
      distress, and severe airway obstruction in the narrow airway of a newborn and
      necessitates urgent surgical intervention. There is only 1 case of congenital
      laryngomucocele reported in an autopsy examination in the English literature, and
      here we report the first living congenital laryngomucocele case and discuss the
      clinical approach. 

PMID- 25974822
TI  - Interdisciplinary treatment for an adult patient with anterior open bite, severe
      periodontitis, and intellectual disability.
AB  - This case report describes the beneficial effects of the interdisciplinary
      treatment of an adult patient with severe skeletal periodontal problems. A 30
      year-old female patient presented with anterior open bite, gummy smile, and
      facial asymmetry. The patient had chronic generalized severe periodontitis with
      pathologic maxillary anterior teeth migration and mild intellectual disability.
      Treatment included 6 months of periodontal treatment, followed by presurgical
      orthodontic treatment, a Le Fort I osteotomy with anterior segmental osteotomy, a
      bilateral sagittal split ramus osteotomy, and postsurgical orthodontic treatment.
      After treatment completion, the patient exhibited functional and aesthetic
      improvements. Her periodontal condition improved and was maintained after the
      treatment. Here, we demonstrate a successful treatment outcome in a complicated
      case following a systematic interdisciplinary approach performed with the correct
      diagnosis and treatment planning. 

PMID- 25974823
TI  - Endoscopic endonasal versus transfacial approach for blowout fractures of the
      medial orbital wall.
AB  - In the last decades, the introduction of computed tomography has allowed an
      increase in the number of diagnosed fractures of the medial orbital wall. To
      repair medial wall fractures, many surgical techniques have been proposed (1),
      each one with its advantages and disadvantages. In this study, we compared
      endoscopic endonasal and transcutaneous reduction approaches in terms of surgery
      time and clinical outcome. Between 2001 and 2005, 81 patients with orbital wall
      fractures were treated at our department. Among these 81 patients, 24 (29.63%)
      were affected by a medial orbital fracture. Patients with fracture to both floor
      and medial walls underwent floor reduction by a transcutaneous subpalpebral
      approach (n = 9, 11.1%), whereas patients with isolated medial wall fracture
      underwent medial wall reduction by a transcutaneous subpalpebral approach using
      alloplastic implants (n = 8, 9.88%) or were treated by endoscopic approach (n =
      5, 6.17%). After surgery, oculomotor function improved in all 22 patients. None
      of the patients had complications. Computed tomography revealed a well
      consolidated site of fracture in both endoscopic endonasal and transcutaneous
      approaches. The average operating time for endoscopic endonasal and transfacial
      approach was 50 and 45 minutes, respectively. In this paper, the author proposed
      a results comparison between the endoscopic approach and the transcutaneous one.

PMID- 25974824
TI  - Extraoral surgical approach of ectopic mandibular third molar to the lower border
      of mandible.
AB  - The surgical removal of impacted lower third molar is an ordinary intervention.
      The treatment of choice in this pathology is an intraoral or, seldom, extraoral
      surgical approach. Various surgical procedures have been described to remove
      ectopic mandibular teeth. The more common technique is an intraoral approach (so
      named "conservative"), even when the tooth is located in an ectopic area.
      However, the "intraoral approach" is often related with the difficulty of view,
      the bleeding of the surgical site, and with the possible lesions of inferior
      alveolar or lingual nerve. From the other side, a nonconservative surgical
      approach like "extraoral pathway" may be associated with no aesthetic cutaneous
      postoperative scar tissue. The aim of those 2 study cases is to highlight the
      management of infected ectopic third molars located close to the lower border of
      the mandibular body, underlining the anatomical land markers of the submandibular
      area. The authors have applied the extraoral pathway using an incision of small
      size. From our analysis, the treatment of those typical can be managed by using a
      "mini-skin-incision" (so termed as mini-submandibular approach) respecting the
      cosmetic expectations of the patients. 

PMID- 25974825
TI  - Unilateral mandibular advancement with bilateral intraoral vertical ramus
      osteotomy.
AB  - Intraoral vertical ramus osteotomy (IVRO) is an effective surgical procedure that
      is used for the correction of mandibular prognathism. However, application of
      IVRO for mandibular advancement has been limited because of the instability of
      the proximal segments caused by the gap between the distal and proximal segments.
      We report a case of unilateral mandibular advancement with bilateral IVRO for the
      correction of facial asymmetry. This case shows possible application of bilateral
      IVRO for unilateral mandibular advancement without any means of fixation. 

PMID- 25974826
TI  - The Le Fort I osteotomy as surgical approach of an extensive pleomorphic adenoma
      of the palate.
AB  - Pleomorphic adenoma (PA) is the most common benign mixed salivary gland tumor. We
      describe here a peculiar case of a 72-year-old woman with a PA of the palate
      resected with palatal approach combined with Le Fort I osteotomy, adding to the
      currently limited scientific literature on intraoral approach for removal of
      extensive tumors of the midface. The Le Fort I osteotomy approach allows direct
      visualization of the tumor and ensures a wide excision, increasing safety and
      minimizing the possibility of recurrence.

PMID- 25974827
TI  - Study of Condylar Asymmetry in Angle Class III Malocclusion With Mandibular
      Deviation.
AB  - OBJECTIVE: Differences in the condylar between both sides in class III cases with
      mandibular deviated are important for the diagnosis, treatment, and retention in
      this kind of patient. To detect the subtle differences, we analyzed the size,
      shape, and bone density with three-dimensional reconstructed technology. METHODS:
      The symmetry group and the asymmetry group each with 20 cases were chosen
      according to some standards. The computed tomographic data obtained and three
      dimensional model were built with SimPlant software. The distance and angle were
      measured in the three-dimensional model, and the bone density was measured with
      the SimPlant software. The differences between the separated side in each group
      and the difference between the 2 groups were analyzed. RESULTS: In the asymmetry
      group, some measurement projects of the bilateral condyles showed significant
      differences, such as the ramal height, condylar perpendicular height, the area of
      maximum cross section of condylar, condylar medialateral diameter, length of
      posterior slope, and angle of posterior slope. When the asymmetry group was
      compared with the symmetry group, the condyles of the asymmetry group showed more
      asymmetrical variations in morphology, such as the ramal height, the condylar
      perpendicular height, the area of maximum cross section of condylar, the
      medialateral diameter, the length of anterior slope, and angle of posterior
      slope. The bone mineral density of the condylar anterior and condylar medial
      point was higher in the nondeviated side, and the bone mineral density of the
      condylar posterior was higher in the deviated side, and no statistically
      significant difference was found in the symmetry group. CONCLUSIONS: In class III
      malocclusion with mandibular deviation patients, the three-dimensional morphology
      and bone density of condylar on the deviated side differ from the nondeviated
      side, which indicates the association between asymmetrical jaw function and joint
      remodeling.

PMID- 25974828
TI  - Investigation of nasal mobility in Asians and its change after alloplastic
      augmentation.
AB  - Augmentation rhinoplasty is one of the most popular cosmetic surgeries in Asia,
      and both dorsal augmentation and mobile nose modifications are emphasized for the
      characters of the Asian nose and for Asians who are fond of the Western nasal
      shape. The goal in rhinoplasty is to create a balanced and natural appearance.
      Therefore, the cosmetic aspects, postoperative complications, and functional
      aspects should be regarded as a whole. In fact, the first 2 aspects had been
      widely reported in a large number of literatures. However, the functional aspects
      about mobility have been ignored by most surgeons. A sample method was used in
      this article to investigate the range of mobility of normal nasal tip in Asians
      and analyze the correlations of the nasal mobility and alloplastic materials. A
      total of 170 healthy adult subjects aged from 18 to 35 were included and were
      classified into 3 groups standing for normal nose and rhinoplasty with L-shaped
      silicon implants with e-PTFE implants. A 3D raster surface scanner was used to
      capture the images of the subjects accurately and rapidly in this detailed
      anatomical study. The range of nasal mobility (to right or left) in Asian normal
      women was 35.53 +/- 4.84 degrees, and the length of mobile part was 16.62 +/-
      1.94  mm, which accounts for 40% +/- 5% of nasal length. The L-shaped alloplastic
      implants would reduce the nasal mobility, and there had been differences among
      the changes caused by different implants, which might cause unsatisfactory
      outcomes in patients. Results of the study indicated that augmentation
      rhinoplasty should be performed as well as augmented mammaplasty which attaches
      importance not only to the static and dynamic appearance of the nasal tip but
      also to the feeling when it is touched.

PMID- 25974829
TI  - Successful conservative management of a large congenital scalp and skull defect.
AB  - The authors report a case of a female baby born with large congenital scalp and
      skull defects with exposure of the cranial arachnoid mater. The female patient
      was delivered by Caesarean section following diagnosis of a large cranial skin
      defect by ultrasound. The skin defect was present at the time of birth, measured
      8.5  cm * 8.0  cm, and involved the full thickness of the cranium. The cranial
      arachnoid mater was exposed and veins running on the surface of the brain were
      observed. There was no means to cover the large defect surgically and
      conservative treatment was initiated. Complete epithelialization of the scalp
      defect was acquired without fatal problems. In the course of treatment, Mepilex
      Transfer was very effective. The repair of congenital defects of the scalp and
      skull is a major challenge not only because of the rarity but also because of
      severe morbidity. A surgical or conservative approach is chosen according to the
      situation. This rare case highlights two important clinical issues: that the
      congenital defects of the scalp and skull could not be managed with a surgical
      approach and in its place, a conservative approach using the special dressing
      Mepilex Transfer proved highly effective.

PMID- 25974830
TI  - The application of a carbon dioxide laser in the treatment of superficial oral
      mucosal lesions.
AB  - To evaluate the safety and advantages of using carbon dioxide (CO2) laser in the
      treatment of oral mucosal lesion, including vascular malformations, precancerous
      lesions, and verrucous nevus, a retrospective analysis was conducted for 73
      patients with oral mucosal lesions who received CO2 laser treatment during June
      2012 to December 2013, including 25 patients with vascular malformations, 22
      patients with oral leukoplakia, 18 patients with oral mucosal lichen planus, and
      8 patients with oral mucosal and labial mucosal verrucous nevus. The lesions
      ranged from 0.8 * 0.8  cm to 4 * 3  cm. Twenty patients with lesions removed
      using the traditional scalpel, assisted with an electric knife, were the control
      group. The operative time was from 3 to 10 minutes, with an average of 5.5
      minutes; the average amount of intraoperative bleeding was 5  mL. None of the 73
      patients had postoperative infections, and all wounds healed well after the
      surgery. The patients were followed up for 1 year. Two patients with oral
      leukoplakia showed recurrence after the surgery, and a reoperation achieved
      satisfactory treatment effects. The operative time of the control group was in
      the range of 4 to 15 minutes, with an average of 9.5 minutes, and the average
      amount of intraoperative bleeding was 10  mL. None of the 20 patients had
      postoperative infections, and the wounds also showed healing well after the
      surgery. The application of CO2 laser in the treatment of oral mucosal lesions
      has the advantages of reduced bleeding, a clear view during surgery, and a
      shorter operative time.

PMID- 25974831
TI  - Sudden hearing loss: a study of prognostic factors for hearing recovery.
AB  - OBJECTIVE: Sudden hearing loss (SHL) is a disease, isolated or associated with
      vertigo, of unknown etiology. The aim of this study was to identify the
      prognostic factors for hearing recovery. METHODS: In this retrospective study, we
      analyzed 287 cases of SHL (mean age 42). Tonal threshold audiometry, BAEP, and RM
      were the diagnostic procedures for clinical balance of the patient. The therapy
      used the following: corticosteroids, osmotic diuretic infusion, and vasoactives.
      All the factors were evaluated through statistical tests, Spearman test, and
      linear logistic regression. RESULTS: In our study, we observed that 39.3% of
      patients improved, 27.9% remained unchanged, 29% had complete recovery, and 3.8%
      worsened. Therapy was not related to the degree of recovery from hearing loss,
      whereas young age, delayed diagnosis, and audiometric curve type were the three
      factors related to the degree of hearing recovery. CONCLUSIONS: In our study, we
      report a better overall recovery rate compared with spontaneous recovery. In
      particular, early treated patients as well as patients with upsloping hearing
      loss frequently recovered after treatment. Age, time between onset and treatment,
      and audiogram type were shown to be significantly related to outcome.

PMID- 25974832
TI  - Investigation of effects of short-term exposure to 50 HZ magnetic field on
      central, peripheral, and autonomic nervous systems in rats.
AB  - Although a large number of exposure studies have been carried out to investigate
      possible detrimental effects of a power-line frequency magnetic field (PF-MF; 50
      60 Hz) on living organisms, there is no consensus in reported results. Recent
      research suggested that short-term exposure to a 50 Hz PF-MF can have a greater
      effect than long-term exposure. In our study, we aimed to investigate the
      possible effect of short-term 50 Hz PF-MF exposure on central, peripheral, and
      autonomic nervous systems through electroencephalogram (EEG), nerve conduction
      velocity (NCV), and heart rate variability (HRV) measurements. To that end,
      Wistar albino rats and sciatic nerves gathered from the rats were exposed to a 50
      Hz, 0.3 mT MF, and changes on EEG, NCV, and HRV were investigated. According to
      data we gathered, MF frequency and magnetic flux density that we applied did not
      affect EEG, NCV, or HRV. The reason for conflicting results gathered from MF
      exposure studies may be that the nervous system can be affected by a specific MF
      frequency and magnetic flux density, but that different MF exposures do not
      affect it. Moreover, exposure duration to MF may also have influenced results.

PMID- 25974833
TI  - X-chromosome inactivation in female patients with Fabry disease.
AB  - Fabry disease (FD) is an X-linked genetic disorder caused by the deficient
      activity of lysosomal alpha-galactosidase (alpha-Gal). While males are usually
      severely affected, clinical presentation in female patients may be more variable
      ranging from asymptomatic to, occasionally, as severely affected as male
      patients. The aim of this study was to evaluate the existence of skewed X
      chromosome inactivation (XCI) in females with FD, its concordance between
      tissues, and its contribution to the phenotype. Fifty-six females with FD were
      enrolled. Clinical and biological work-up included two global scores [Mainz
      Severity Score Index (MSSI) and DS3], cardiac magnetic resonance imaging,
      measured glomerular filtration rate, and measurement of alpha-Gal activity. XCI
      was analyzed in four tissues using DNA methylation studies. Skewed XCI was found
      in 29% of the study population. A correlation was found in XCI patterns between
      blood and the other analyzed tissues although some punctual variability was
      detected. Significant differences in residual alpha-Gal levels, severity scores,
      progression of cardiomyopathy and deterioration of kidney function, depending on
      the direction and degree of skewing of XCI were evidenced. XCI significantly
      impacts the phenotype and natural history of FD in females. 

PMID- 25974834
TI  - Knowing Who Knows: Laypersons' Capabilities to Judge Experts' Pertinence for
      Science Topics.
AB  - Because modern societies are built on elaborate divisions of cognitive labor,
      individuals remain laypersons in most knowledge domains. Hence, they have to rely
      on others' expertise when deciding on many science-related issues in private and
      public life. Even children already locate and discern expertise in the minds of
      others (e.g., Danovitch & Keil, 2004). This study examines how far university
      students accurately judge experts' pertinence for science topics even when they
      lack proficient knowledge of the domain. Participants judged the pertinence of
      experts from diverse disciplines based on the experts' assumed contributions to
      texts adapted from original articles from Science and Nature. Subjective
      pertinence judgments were calibrated by comparing them with bibliometrics of the
      original articles. Furthermore, participants' general science knowledge was
      controlled. Results showed that participants made well-calibrated pertinence
      judgments regardless of their level of general science knowledge. 

PMID- 25974835
TI  - A Bioorthogonal Chemical Reporter of Viral Infection.
AB  - Pathogen-selective labeling was achieved by using the novel gemcitabine
      metabolite analogue 2'-deoxy-2',2'-difluoro-5-ethynyluridine (dF-EdU) and click
      chemistry. Cells infected with Herpes Simplex Virus-1 (HSV-1), but not uninfected
      cells, exhibit nuclear staining upon the addition of dF-EdU and a fluorescent
      azide. The incorporation of the dF-EdU into DNA depends on its phosphorylation by
      a herpes virus thymidine kinase (TK). Crystallographic analyses revealed how dF
      EdU is well accommodated in the active site of HSV-1 TK, but steric clashes
      prevent dF-EdU from binding human TK. These results provide the first example of
      pathogen-enzyme-dependent incorporation and labeling of bioorthogonal functional
      groups in human cells. 

PMID- 25974836
TI  - A family of lanthanide-based coordination polymers with boronic Acid as ligand.
AB  - Reactions in water between the sodium salt of 4-carboxyphenylboronic acid (Hcpb)
      and lanthanide ions (Pr-Nd, Sm-Lu, and Y) led to a family of lanthanide-based
      coordination polymers with general chemical formula
      {[Ln(cpbOH)(H2O)2](cpb)}infinity. Structural characterizations were ensured by
      single-crystal X-ray diffraction and solid-state NMR spectroscopy ((11)B, (13)C,
      and (89)Y). This family of compounds constitutes the first example of lanthanide
      based coordination polymers involving 4-carboxyphenylboronic acid as ligand. To
      evaluate their potential usefulness, luminescent and magnetic properties of some
      of the compounds that constitute this family were explored. From a magnetic point
      of view, the Yb(III) compound is the more promising. On the other hand, upon UV
      irradiation (lambdaexc = 303 nm) ligand phosphorescence is quite intense and
      offers a sizable blue component to emission spectra. This is quite unusual and
      can constitute an asset as far as white emission is targeted. Moreover,
      luminescence properties of these compounds are highly temperature-dependent, and
      some of them seem promising as molecular thermometers. 

PMID- 25974837
TI  - Incidence and Causes of Aconitum Alkaloid Poisoning in Hong Kong from 1989 to
      2010.
AB  - Aconite roots contain Aconitum alkaloids, which are highly toxic cardiotoxins and
      neurotoxins. In this review, the main objective was to determine the incidence
      and causes of Aconitum alkaloid poisoning in Hong Kong between 1989 and 2010,
      based on six published reports from the territory-wide poison control units. In
      the New Territories East of Hong Kong, the incidence of aconite poisoning showed
      a sudden and sustained decrease from 0.60 (1989-1991) to 0.16 (1992-1993) and
      0.17 (1996-1998) per 100 000 population, after publicity measures in late 1991 to
      promote awareness of the toxicity of aconite roots. In the whole of Hong Kong,
      the incidence of aconite poisoning was even lower in January 2000-June 2004 (0.03
      per 100 000 population). However, aconite poisoning became more common again in
      April 2004-July 2009 and 2008-2010 (0.15 and 0.28 per 100 000 population).
      Overdoses and use of inadequately processed aconite roots were important causes.
      As from 2004 to 2009, 'hidden' aconite poisoning (toxicity caused by contaminants
      in other dispensed herbs) emerged as an important cause. It is important to
      continue the safety monitoring of potent herbs and the networking of poison
      control units. Further systematic studies would be required to identify the
      likely sources of contamination of herbs.

PMID- 25974838
TI  - Intravenous lipid emulsion therapy in three cases of canine naproxen overdose.
AB  - OBJECTIVE: To report a case series of canine naproxen overdoses successfully
      treated with intravenous lipid emulsion therapy (IVLE). SERIES SUMMARY: Three
      dogs were presented for acute ingestion of naproxen and were treated with IVLE.
      Baseline and post treatment serum naproxen concentrations were measured. The
      first exposure involved ingestion of 61 mg/kg of an over-the-counter naproxen
      formulation in a 7-month-old male intact Labrador Retriever. Pre-IVLE toxin
      concentration assessed by high performance liquid chromatography (HPLC) was 73
      MUg/mL with a one-hour post-IVLE concentration decreasing to 30 MUg/mL. The
      second and third exposures were 3-year-old female spayed Pembroke Welsh Corgi
      dogs from the same family, presented for potential ingestion of up to 207 mg/kg
      of a prescription strength naproxen formulation. Pre-IVLE naproxen concentration
      by HPLC for case 2 was 30 MUg/mL with a reduction to 12 MUg/mL and 7.2 MUg/mL 1
      and 3 hours post-IVLE treatment, respectively. For case 3, pre-IVLE naproxen
      concentration by HPLC was 86 MUg/mL with post concentrations at 21 MUg/mL one
      hour and 10 MUg/mL 3 hours post-IVLE administration. NEW OR UNIQUE INFORMATION
      PROVIDED: Naproxen is a nonsteroidal anti-inflammatory drug with a long half-life
      and narrow margin of safety in dogs. Ingestion of > 5 mg/kg has been associated
      with adverse gastrointestinal effects, including ulceration. At doses > 10-25
      mg/kg, acute kidney failure has been reported, and at doses > 50 mg/kg,
      neurologic abnormalities occur. This is the first reported use of IVLE for
      treatment of naproxen overdose with documented decrease in serum toxin
      concentrations shortly after administration. No long-standing gastrointestinal,
      renal, or neurologic effects occurred in these dogs.

PMID- 25974839
TI  - Quantitative investigation of the poly-adenine DNA dissociation from the surface
      of gold nanoparticles.
AB  - In recent years, poly adenine (polyA) DNA functionalized gold nanoparticles
      (AuNPs) free of modifications was fabricated with high density of DNA attachment
      and high hybridization ability similar to those of its thiolated counterpart.
      This nanoconjugate utilized poly adenine as an anchoring block for binding with
      the AuNPs surface thereby facilitated the appended recognition block a better
      upright conformation for hybridization, demonstrating its great potential to be a
      tunable plasmonic biosensor. It's one of the key points for any of the practical
      applications to maintaining stable conjugation between DNA oligonucleotides and
      gold nanoparticles under various experimental treatments. Thus, in this research,
      we designed a simple but sensitive fluorescence turn-on strategy to
      systematically investigate and quantified the dissociation of polyA DNA on gold
      nanoparticles in diverse experimental conditions. DNA desorbed spontaneously as a
      function of elevated temperature, ion strength, buffer pH, organic solvents and
      keeping time. What's more, evaluating this conjugate stability as affected by the
      length of its polyA anchor was another crucial aspect in our study. With the
      improved understanding from these results, we were able to control some of our
      experimental conditions to maintain a good stability of this kind of polyA DNA
      AuNPs nanoconjugates. 

PMID- 25974840
TI  - A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade
      reaction of isoindigos: construction of chiral bispirooxindole
      tetrahydrothiophenes with vicinal quaternary spirocenters.
AB  - A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa
      Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has
      been successfully developed to afford the highly congested bispirooxindole
      tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to
      91%), excellent diastereoselectivities (up to >20 : 1 dr), and good
      enantioselectivities (up to 98% ee). Some synthetic transformations of the
      reaction products were also studied. 

PMID- 25974841
TI  - Correction: GOBLET: The Global Organisation for Bioinformatics Learning,
      Education and Training.

PMID- 25974842
TI  - Rat rotator cuff muscle responds differently from hindlimb muscle to a combined
      tendon-nerve injury.
AB  - Rotator cuff tears (RCTs) are among the most common musculoskeletal injuries seen
      by orthopaedic surgeons. Clinically, massive cuff tears lead to unique
      pathophysiological changes in rotator cuff muscle, including atrophy, and massive
      fatty infiltration, which are rarely seen in other skeletal muscles. Studies in a
      rodent model for RCT have demonstrated that these histologic findings are
      accompanied by activation of the Akt/mammalian target of rapamycin (mTOR) and
      transforming growth factor-beta (TGF-beta) pathways following combined tendon
      nerve injury. The purpose of this study was to compare the histologic and
      molecular features of rotator cuff muscle and gastrocnemius muscle--a major
      hindlimb muscle, following combined tendon-nerve injury. Six weeks after injury,
      the rat gastrocnemius did not exhibit notable fatty infiltration compared to the
      rotator cuff. Likewise, the adipogenic markers SREBP-1 and PPARgamma as well as
      the TGF-beta canonical pathway were upregulated in the rotator cuff, but not the
      gastrocnemius. Our study suggests that the rat rotator cuff and hindlimb muscles
      differ significantly in their response to a combined tendon-nerve injury.
      Clinically, these findings highlight the unique response of the rotator cuff to
      injury, and may begin to explain the poor outcomes of massive RCTs compared to
      other muscle-tendon injuries.

PMID- 25974843
TI  - Sclerostin antibody preserves the morphology and structure of osteocytes and
      blocks the severe skeletal deterioration after motor-complete spinal cord injury
      in rats.
AB  - Unloading, neural lesions, and hormonal disorders after acute motor-complete
      spinal cord injury (SCI) cause one of the most severe forms of bone loss, a
      condition that has been refractory to available interventions tested to date.
      Thus, these features related to acute SCI provide a unique opportunity to study
      complex bone problems, potential efficacious interventions, and mechanisms of
      action that are associated with these dramatic pathological changes. This study
      was designed to explore the therapeutic potential of sclerostin antibody (Scl-Ab)
      in a rat model of bone loss after motor-complete SCI, and to investigate
      mechanisms underlying bone loss and Scl-Ab action. SCI rats were administered Scl
      Ab (25 mg/kg/week) or vehicle beginning 7 days after injury then weekly for 7
      weeks. SCI resulted in significant decreases in bone mineral density (-25%) and
      trabecular bone volume (-67%) at the distal femur; Scl-Ab completely prevented
      these deteriorations of bone in SCI rats, concurrent with markedly increased bone
      formation. Scanning electron microscopy revealed that SCI reduced numbers of
      osteocytes and dendrites concomitant with a morphology change from a spindle to
      round shape; Scl-Ab corrected these abnormalities in osteocytes. In ex vivo
      cultures of bone marrow cells, Scl-Ab inhibited osteoclastogenesis, and promoted
      osteoblastogenesis accompanied by increases in mRNA levels of LRP5,
      osteoprotegerin (OPG), and the OPG/RANKL ratio, and a decrease in DKK1 mRNA. Our
      findings provide the first evidence that robust bone loss after acute motor
      complete SCI can be blocked by Scl-Ab, at least in part, through the preservation
      of osteocyte morphology and structure and related bone remodeling. Our findings
      support the inhibition of sclerostin as a promising approach to mitigate the
      striking bone loss that ensues after acute motor-complete SCI, and perhaps other
      conditions associated with disuse osteoporosis as a consequence of neurological
      disorders.

PMID- 25974844
TI  - Clinical Operations Variables are Associated With Blood Pressure Outcomes.
AB  - BACKGROUND: Uncontrolled blood pressure (BP), among patients diagnosed and
      treated for the condition, remains an important clinical challenge; aspects of
      clinical operations could potentially be adjusted if they were associated with
      better outcomes. OBJECTIVES: To assess clinical operations factors' effects on
      normalization of uncontrolled BP. RESEARCH DESIGN: Observational cohort study.
      SUBJECTS: Patients diagnosed with hypertension from a large urban clinical
      practice (2005-2009). MEASURES: We obtained clinical data on BP, organized by
      person-month, and administrative data on primary care provider (PCP) staffing. We
      assessed the resolution of an episode of uncontrolled BP as a function of time
      varying covariates including practice-level appointment volume, individual
      clinicians' appointment volume, overall practice-level PCP staffing, and number
      of unique PCPs. RESULTS: Among the 7409 unique patients representing 50,403
      person-months, normalization was less likely for the patients in whom the episode
      starts during months when the number of unique PCPs were high [the top quintile
      of unique PCPs was associated with a 9 percentage point lower probability of
      normalization (P<0.01) than the lowest quintile]. Practice appointment volume
      negatively affected the likelihood of normalization [episodes starting in months
      with the most appointments were associated with a 6 percentage point reduction in
      the probability of normalization (P=0.01)]. Neither clinician appointment volume
      nor practice clinician staffing levels were significantly associated with the
      probability of normalization. CONCLUSIONS: Findings suggest that clinical
      operations factors can affect clinical outcomes like BP normalization, and point
      to the importance of considering outcome effects when organizing clinical care.

PMID- 25974845
TI  - Poly-L-Lysine-Poly[HPMA] Block Copolymers Obtained by RAFT Polymerization as
      Polyplex-Transfection Reagents with Minimal Toxicity.
AB  - Herein we describe the synthesis of poly-L-lysine-b-poly[N-(2-hydroxypropyl)
      metha-crylamide)] (poly[HPMA]) block copolymers by combination of solid phase
      peptide synthesis or polymerization of alpha-amino acid-N-carboxy-anhydrides (NCA
      polymerization) with the reversible addition-fragmentation chain transfer
      polymerization (RAFT). In the presence of p-DNA, these polymers form polyplex
      micelles with a size of 100-200 nm in diameter (monitored by SDS-PAGE and FCS).
      Primary in vitro studies with HEK-293T cells reveal their cellular uptake (FACS
      studies and CLSM) and proof successful transfection with efficiencies depending
      on the length of polylysine. Moreover, these polyplexes display minimal toxicity
      (MTT-assay and FACS-measurements) featuring a p[HPMA] corona for efficient
      extracellular shielding and the potential ligation with antibodies.

PMID- 25974846
TI  - Cutting edge.

PMID- 25974847
TI  - Balance-billing ban back in 2015 legislature.

PMID- 25974848
TI  - Standing up for patients.

PMID- 25974849
TI  - Room to grow.

PMID- 25974850
TI  - We got it wrong.

PMID- 25974851
TI  - The next phase of cancer care.

PMID- 25974852
TI  - A novel rhamno-mannan exopolysaccharide isolated from biofilms of Burkholderia
      multivorans C1576.
AB  - Burkholderia multivorans C1576 is a Gram negative opportunistic pathogen causing
      serious lung infection in cystic fibrosis patients. Considering that bacteria
      naturally form biofilms, and exopolysaccharides are recognized as important
      factors for biofilm architecture set-up, B. multivorans was grown both in biofilm
      and in non-biofilm mode on two different media in order to compare the
      exopolysaccharides biosynthesized in these different experimental conditions. The
      exopolysaccharides produced were purified and their structure was determined
      resorting mainly to NMR spectroscopy, ESI mass spectrometry and gas
      chromatography coupled to mass spectrometry. The experimental data showed that
      both in biofilm and non-biofilm mode B. multivorans C1576 produced a novel
      exopolysaccharide having the following structure: [Formula: see text]. About 50%
      of the 2-linked rhamnose residues are substituted on C-3 with a methyl ether
      group. The high percentage of deoxysugar Rha units, coupled with OMe
      substitutions, suggest a possible role for polymer domains with marked
      hydrophobic characteristics able to create exopolysaccharide junction zones
      favouring the stability of the biofilm matrix.

PMID- 25974853
TI  - Structural analysis of novel trehalose-based oligosaccharides from extremely
      stress-tolerant ascospores of Neosartorya fischeri (Aspergillus fischeri).
AB  - Different fungi, including the genera Neosartorya, Byssochlamys and Talaromyces,
      produce (asco)spores that survive pasteurization treatments and are regarded as
      the most stress-resistant eukaryotic cells. Here, the NMR analysis of a series of
      trehalose-based oligosaccharides, being compatible solutes that are accumulated
      to high levels in ascospores of the fungus Neosartorya fischeri, is presented.
      These oligosaccharides consist of an alpha,alpha-trehalose backbone, extended
      with one [alpha-D-Glcp-(1 -> 6)-alpha-D-Glcp-(1 <-> 1)-alpha-D-Glcp;
      isobemisiose], two [alpha-D-Glcp-(1 -> 6)-alpha-D-Glcp-(1 -> 6)-alpha-D-Glcp-(1 <
      > 1)-alpha-D-Glcp] or three [alpha-D-Glcp-(1 -> 6)-alpha-D-Glcp-(1 -> 6)-alpha-D
      Glcp-(1 -> 6)-alpha-D-Glcp-(1 <-> 1)-alpha-D-Glcp] glucose units. The tetra- and
      pentasaccharide, dubbed neosartose and fischerose, respectively, have not been
      reported before to occur in nature.

PMID- 25974854
TI  - Synthesis of spirofused carbohydrate-oxazoline based palladium(II) complexes.
AB  - Four carbohydrate-derived 2-pyridyl and 2-quinolinyl substituted spiro-oxazoline
      ligands were prepared from 3,4,5-tri-O-benzyl-1,2-di-O-isopropylidene-beta-D
      fructose in four steps. Conversion of the latter compound with
      trimethylsilylazide followed by hydrogenation gave an anomeric mixture of 2-amino
      3,4,5-tri-O-benzyl-2-deoxy-1-O-trimethylsilyl-D-fructopyranose. Amide coupling of
      the fructosylamines with picolinic acid and quinaldic acid, respectively afforded
      the corresponding anomeric amidofructosides, which were both separated and
      characterized by NMR spectroscopy and X-ray crystallography. Cyclization of alpha
      amides was achieved by treatment of the corresponding mesylates with NaH while
      beta-amides were directly cyclisized with NCS and Ph3P to give the corresponding
      2-pyridyl (PyOx) and 2-quinolyl (QuinOx) substituted spiro-oxazoline ligands,
      respectively. The 2-pyridyl substituted spiro-oxazoline ligands PyOx formed
      stable complexes with Pd(II), which were fully characterized and their structure
      determined by X-ray crystallography, whereas the corresponding QuinOx ligands
      failed to form similar Pd complexes.

PMID- 25974856
TI  - Exploring experimental and computational markers of cyclic peptides: Charting
      islands of permeability.
AB  - An increasing number of macrocyclic peptides that cross biological membranes are
      being reported, suggesting that it might be possible to develop peptides into
      orally bioavailable therapeutics; however, current understanding of what makes
      macrocyclic peptides cell permeable is still limited. Here, we synthesized 62
      cyclic hexapeptides and characterized their permeability using in vitro assays
      commonly used to predict in vivo absorption rates, i.e. the Caco-2 and PAMPA
      assays. We correlated permeability with experimentally measured parameters of
      peptide conformation obtained using rapid methods based on chromatography and
      nuclear magnetic resonance spectroscopy. Based on these correlations, we propose
      a model describing the interplay between peptide permeability, lipophilicity and
      hydrogen bonding potential. Specifically, peptides with very high permeability
      have high lipophilicity and few solvent hydrogen bond interactions, whereas
      peptides with very low permeability have low lipophilicity or many solvent
      interactions. Our model is supported by molecular dynamics simulations of the
      cyclic peptides calculated in explicit solvent, providing a structural basis for
      the observed correlations. This prospective exploration into biomarkers of
      peptide permeability has the potential to unlock wider opportunities for
      development of peptides into drugs. 

PMID- 25974855
TI  - Prognostic value of meta-signature miRNAs in renal cell carcinoma: an integrated
      miRNA expression profiling analysis.
AB  - To identify a robust panel of microRNA (miRNA) signatures that can distinguish
      renal cell carcinoma (RCC) from normal kidney using miRNA expression levels. We
      performed a comprehensive meta-analysis of 29 published studies that compared the
      miRNA expression profiles of RCC tissues and adjacent normal tissues (NT) to
      determine candidate miRNAs as prognostic biomarkers for RCC. Using vote-counting
      strategy and robust rank aggregation method, we identified a statistically
      significant miRNA meta-signature of two upregulated (miR-21, miR-210) and three
      downregulated (miR-141, miR-200c and miR-429) miRNAs. X-tile plot was used to
      generate the optimum cut-off point for the 15 different deregulated miRNAs and
      Kaplan-Meier method was used to calculate CSS. In a cohort of 45 patients, the
      high expression of miR-21 (HR: 5.46, 95%CI: 2.02-53.39) and miR-210 (HR: 6.85,
      95%CI: 2.13-43.36), the low expression of miR-141 (HR: 0.16, 95%CI: 0.004-0.18),
      miR-200c (HR: 0.08, 95%CI: 0.01-0.43) and miR-429 (HR: 0.18, 95%CI: 0.02-0.50)
      were associated with poor cancer-specific survival (CSS) following RCC resection.
      We also constructed a five-miRNAs-based classifier as a reliable prognostic and
      predictive tool for CSS in patients with RCC, especially in clear cell RCC
      (ccRCC) (HR: 5.46, 95% CI: 1.51-19.66). This method might facilitate patient
      counselling and individualise management of RCC. 

PMID- 25974857
TI  - Reduction of Working Time: Does It Lead to a Healthy Lifestyle?
AB  - I examine whether working hours have a causal effect on the health behaviors of
      workers. In assessing the causal relationship, I estimate fixed-effects
      instrumental variable models by using exogenous variation in adopting a reduced
      workweek in South Korea as an instrument for work hours. The estimation results
      reveal that shortening work hours induces individuals to exercise regularly and
      decreases the likelihood of smoking, with more pronounced effects for heavy
      smokers. While a work-hour reduction substantially increases the probability of
      drinking participation, it does not significantly affect the likelihood of
      frequent or daily drinking habits. In addition, the effect of a work-hour
      reduction on regular exercise is salient among women and older groups, and the
      effect on smoking behaviors is more pronounced among men and middle-aged groups.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25974858
TI  - Characterization of Laves phase in Crofer 22 H stainless steel.
AB  - This study investigated the effect of annealing temperature on the precipitation
      behavior of Crofer((r)) 22 H at 600 degrees C, 700 degrees C, and 800 degrees C.
      The grain size distribution, precipitate phase identification, and microstructure
      were analyzed using electron backscatter diffraction (EBSD) and energy dispersive
      X-ray spectroscopy (EDS). The morphology of Laves phase (Fe,Cr,Si)(2)(Nb,W)
      precipitates having the Cr(2)Nb structure changed from strip-like to needle
      shaped as the annealing temperature was increased. The precipitates of the Laves
      phase also shifted from the grain boundaries to the grain interiors when the
      temperature was increased. However, the average grain size (150 MUm) of the
      ferritic matrix did not significantly change at 600 degrees C, 700 degrees C, and
      800 degrees C for 10 h.

PMID- 25974859
TI  - Oxaliplatin vs. cisplatin: competition experiments on their binding to lysozyme.
AB  - The model protein hen egg white lysozyme was challenged with oxaliplatin and
      cisplatin. ESI mass spectrometry, surface plasmon resonance and thermal shift
      analyses demonstrate the formation of a bis-platinum adduct, though in very small
      amounts. Crystals of the bis-platinum adduct were obtained using two different
      preparations and the X-ray structures were solved at 1.85 A and 1.95 A
      resolution. Overall, the obtained data point out that, under the analyzed
      conditions, the two Pt drugs have similar affinities for the protein, but bind on
      its surface at two non-overlapping sites. In other words, these two drugs
      manifest a significantly different reactivity with this model protein and do not
      compete for the same protein binding sites. 

PMID- 25974860
TI  - High-Performance Liquid Chromatographic Enantioseparation of Cyclic beta-Amino
      Acids on Zwitterionic Chiral Stationary Phases Based on Cinchona Alkaloids.
AB  - Stereoselective high-performance liquid chromatographic separations of eight
      sterically constrained cyclic beta-amino acid enantiomer pairs were carried out
      using the newly developed Cinchona alkaloid-based zwitterionic chiral stationary
      phases Chiralpak ZWIX(+) and ZWIX(-). The effects of the mobile phase
      composition, the nature and concentrations of the acid and base additives, the
      counterions and temperature on the separations were investigated. The changes in
      standard enthalpy, Delta(DeltaH degrees ), entropy, Delta(DeltaS degrees ), and
      free energy, Delta(DeltaG degrees ), were calculated from the linear van't Hoff
      plots derived from the ln alpha vs. 1/T curves in the studied temperature range
      (10-50 degrees C). The values of the thermodynamic parameters depended on the
      nature of the selectors and the structures of the analytes. Unusual temperature
      behavior was observed on the ZWIX(-) column: decreased retention times were
      accompanied by increased separation factors with increasing temperature. On the
      ZWIX(+) column only enthalpically, whereas on the ZWIX(-) column both
      enthalpically and entropically driven separations were observed. The elution
      sequence was determined in all cases and was observed to be the opposite on
      ZWIX(+) and on ZWIX(-).

PMID- 25974861
TI  - Fluorescence in robotic surgery.
AB  - Currently, there are several clinical applications for intraoperative ICG, such
      as identification of vascular and biliary anatomy, assessment of organ and tissue
      perfusion, lymph node mapping, and real-time identification of lesions. In this
      paper we present a review of the available literature related to the use of ICG
      fluorescence in robotic surgery in order to provide a better understanding of the
      current applications, show the rapid growth of this technique, and demonstrate
      the potential future applications.

PMID- 25974862
TI  - Synthesis, Electrochemistry, and Single-Molecule Conductance of Bimetallic
      2,3,5,6-Tetra(pyridine-2-yl)pyrazine-Based Complexes.
AB  - The ligands 4'-(4-(methylthio)phenyl)-2,2':6',2"-terpyridine (L(1)), 4'-((4
      (methylthio)phenyl)ethynyl)- 2,2':6',2"-terpyridine (L(2)), and bis(tridentate)
      bridging ligand 2,3,5,6-tetra(pyridine-2-yl)pyrazine (tpp) were used to prepare
      the complexes [Ru(L(1))2][PF6]2 ([1][PF6]2, [Ru(L(2))2][PF6]2 ([2][PF6]2),
      [{(L(1))Ru}(MU-tpp){Ru(L(1))}][PF6]4 ([3][PF6]4), and [{(L(2))Ru}(MU
      tpp){Ru(L(2))}][PF6]4 ([4][PF6]4). Crystallographically determined structures
      give S...S distances of up to 32.0 A in [4](4+). On the basis of electrochemical
      estimates, the highest occupied molecular orbitals of these complexes fall
      between -5.55 and -5.85 eV, close to the work function of clean gold (5.1-5.3
      eV). The decay of conductance with molecular length across this series of
      molecules is approximately exponential, giving rise to a decay constant (pseudo
      beta-value) of 1.5 nm(-1), falling between decay factors for oligoynes and
      oligophenylenes. The results are consistent with a tunnelling mechanism for the
      single-molecule conductance behavior. 

PMID- 25974863
TI  - Rescue Coronary Artery Bypass Grafting in a Neonate After Arterial Switch
      Operation: A Temporary or a Lifetime Solution?
AB  - We describe a case where prompt myocardial rescue revascularization at the time
      of arterial switch operation (ASO) for D-transposition of the great arteries (D
      TGA) was fundamental for overcoming the acute intraoperative myocardial injury
      and for restoring prompt left ventricular function. Five years following the ASO
      the patient was asymptomatic but signs of myocardial ischemia were found at SPECT
      MI, potentially leading to ischemic complications. Adult patients who required
      coronary revascularization in the neonatal period need to be followed for life to
      prevent and treat any possible cause of further myocardial ischemia during
      childhood and adulthood.

PMID- 25974864
TI  - Theoretical study of decomposition of methanediol in aqueous solution.
AB  - Methanediol is a product of the hydration of formaldehyde and is more abundant
      than formaldehyde in aqueous solution. We carried out a number of quantum
      chemical simulations to study the decomposition of methanediol in aqueous
      solution. The decomposition of a methanediol proceeds by transferring a proton
      from a hydroxyl to an oxygen atom of the other hydroxyl in the methanediol. The
      decomposition of the methanediol completes after the cleavage of the bond between
      the formaldehyde and the water molecule. The probability of the proton transfer
      increases by the quantum mechanical tunneling at the low temperature because the
      width of the potential barrier for the decomposition becomes similar to the de
      Broglie wavelength of the proton. We consider the catalytic effect of water
      molecules in aqueous solution. The structure of the methanediol is not required
      to change significantly when undergoing decomposition due to the active role of
      water molecules to transfer a proton. We consider three types of arrangement for
      water molecules with respect to a methanediol: (1) a ring structure formed by a
      methanediol and water molecules; (2) a water cluster attracted to a methanediol
      by hydrogen bonds; and (3) a water cluster and additional water molecules, both
      of which are attracted to a methanediol by hydrogen bonds. The activation energy
      for the decomposition is reduced by a water cluster more efficiently than water
      molecules in a ring structure. However, the activation energy reduced by a water
      cluster is still larger than that obtained from laboratory experiments. We
      include water molecules that are attracted to a methanediol by hydrogen bonds
      during the water-cluster-catalyzed decomposition of a methanediol. The hydrogen
      bonds with the water molecules permit little change in the structure of the
      methanediol during the decomposition and play a significant role to reduce the
      activation energy for the decomposition. The rate constant obtained from the
      theoretical simulation agrees well with that determined by the laboratory
      experiment. 

PMID- 25974865
TI  - RNA-binding residues in the N-terminus of APOBEC3G influence its DNA sequence
      specificity and retrovirus restriction efficiency.
AB  - APOBEC3G (A3G) is a host-expressed protein that inactivates retroviruses through
      the mutagenic deamination of cytosines (C) to uracils (U) in single-stranded DNA
      (ssDNA) replication products. A3G prefers to deaminate cytosines preceded by a
      cytosine (5'CC), whereas all other A3 proteins target cytosines in a 5'TC motifs.
      Structural and mutational studies have mapped the dinucleotide deamination
      preference of A3G to residues in loop 7 of the catalytic C-terminal domain of the
      protein. Here we report that A3G with a double W94A/W127A substitution in its N
      terminus, designed to abolish RNA binding and protein oligomerization, alters the
      DNA deamination specificity of the enzyme from 5'CC to 5'TC on proviral DNA. We
      also show that the double substitution severely impairs its deaminase and
      antiretroviral activities on Vif-deficient HIV-1. Our results highlight that the
      N-terminal domain of the full length A3G protein has an important influence on
      its DNA sequence specificity and mutator activity. 

PMID- 25974867
TI  - Properties of satellite tobacco mosaic virus phenotypes expressed in the presence
      and absence of helper virus.
AB  - In this study, we assembled an Agrobacterium-based transient expression system
      for the ectopic expression of Satellite tobacco mosaic virus (STMV) (+) or (-)
      transcripts and their biological activity was confirmed when Nicotiana
      benthamiana plants were co-expressed with helper Tobacco mosaic virus replicase.
      Characterization of STMV in the presence and absence of its HV revealed: (i) HV
      dependent expression of STMV (+) in N. benthamiana, but not in N. tabacum,
      generated a replication-deficient but translation and encapsidation competent
      variant lacking the highly conserved 3' 150 nucleotides (nt) (STMVDelta150); (ii)
      mutational analysis demonstrated that a conserved 3' stem-loop structure in wild
      type and STMVDelta150 located between nt 874 and 897 is essential for translation
      of CP; (iii) helper virus-independent expression of CP from wt STMV was competent
      for the assembly of empty aberrant virion-like particles; whereas, CP translated
      from STMVDelta150 resulted in disorganized CP aggregates suggesting a role for
      the 3'tRNA-like structure in STMV assembly. 

PMID- 25974866
TI  - Rapid evolution of in vivo-selected sequences and structures replacing 20% of a
      subviral RNA.
AB  - The 356 nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) is
      composed of 5' sequences from a second TCV satRNA (satD) and 3' sequences derived
      from TCV. SHAPE structure mapping revealed that 76 nt in the poorly-characterized
      satD-derived region form an extended hairpin (H2). Pools of satC in which H2 was
      replaced with 76, 38, or 19 random nt were co-inoculated with TCV helper virus
      onto plants and satC fitness assessed using in vivo functional selection (SELEX).
      The most functional progeny satCs, including one as fit as wild-type, contained a
      38-39 nt H2 region that adopted a hairpin structure and exhibited an increased
      ratio of dimeric to monomeric molecules. Some progeny of satC with H2 deleted
      featured a duplication of 38 nt, partially rebuilding the deletion. Therefore, H2
      can be replaced by a 38-39 nt hairpin, sufficient for overall structural
      stability of the 5' end of satC.

PMID- 25974868
TI  - Leucine residues in conserved region of 33K protein of bovine adenovirus - 3 are
      important for binding to major late promoter and activation of late gene
      expression.
AB  - The L6 region of bovine adenovirus 3 (BAdV-3) encode 33K (spliced) and 22K
      (unspliced) proteins. Earlier, anti-33K serum detected five major and three minor
      proteins in BAdV-3 infected cells. Here, we demonstrate that anti-sera raised
      against L6-22K protein detected two proteins of 42 and 37 kDa in BAdV-3 infected
      cells and one protein of 42 kDa in transfected cells expressing splice-site
      variant 22K protein (pC.22K containing substituted splice acceptor/donor
      sequence). Unlike 22K, 33K stimulated the transcription from the major late
      promoter (MLP) by binding to the downstream sequence elements (DE). Analysis of
      the variant proteins demonstrated that amino acids 201-240 of the conserved C
      terminus of 33K containing the potential leucine zipper and RS repeat are
      required for the activation of MLP. Furthermore, amino acid substitution analysis
      demonstrated that unlike arginine residues of RS repeat, the leucine residues
      (217, 224, 232 and 240) of the conserved leucine zipper appear required for the
      binding of 33K to the MLP.

PMID- 25974869
TI  - Benchmark study on glyphosate-resistant cropping systems in the United States.
      Part 7: Effects of weed management strategy (grower practices versus academic
      recommendations) on the weed soil seedbank over 6 years.
AB  - BACKGROUND: Shifts in weed species composition and richness resulting from near
      exclusive reliance on herbicides in glyphosate-resistant (GR) cropping systems
      has necessitated the implementation of alternative weed management tactics to
      reduce selection pressures of herbicides. We contrasted the response of the weed
      soil seedbank to effects of weed management strategy, comparing grower practices
      with academic recommendations for best management practices (BMPs) over 6 years
      and across five weed hardiness zones in the US Midwest at sites subject to GR
      cropping systems. RESULTS: Total weed population density and species richness
      varied according to cropping system, location and prior year's crop, but less so
      to weed management strategy. The seedbank population density for 11 of the 14
      most frequent weed species was affected by weed management strategy either alone
      or in an interaction with hardiness zone or year, or both. In only 29% of
      comparisons was weed population density lower following academic recommendations,
      and this depended upon prior crop and cropping system. The population density of
      high-risk weed species was reduced by academic recommendations, but only in two
      of six years and under continuous GR maize. Overall, the weed population density
      was decreasing in field halves subject to the BMPs in the academic
      recommendations relative to grower practices. CONCLUSION: The soil seedbank is
      slow to respond to academic recommendations to mitigate glyphosate-resistant
      weeds, but represents a biological legacy that growers need to keep in mind even
      when management practices reduce emerged field weed population densities.

PMID- 25974870
TI  - A factor converting viable but nonculturable Vibrio cholerae to a culturable
      state in eukaryotic cells is a human catalase.
AB  - In our previous work, we demonstrated that viable but nonculturable (VBNC) Vibrio
      cholerae O1 and O139 were converted to culturable by coculture with eukaryotic
      cells. Furthermore, we isolated a factor converting VBNC V. cholerae to
      culturable (FCVC) from a eukaryotic cell line, HT-29. In this study, we purified
      FCVC by successive column chromatographies comprising UNO Q-6 anion exchange, Bio
      Scale CHT2-1 hydroxyapatite, and Superdex 200 10/300 GL. Homogeneity of the
      purified FCVC was demonstrated by SDS-PAGE. Nano-LC MS/MS analysis showed that
      the purified FCVC was a human catalase. An experiment of RNAi knockdown of
      catalase mRNA from HT-29 cells and treatment of the purified FCVC with a catalase
      inhibitor, 3-amino-1,2,4-triazole confirmed that the FCVC was a catalase. A
      possible role of the catalase in converting a VBNC V. cholerae to a culturable
      state in the human intestine is discussed.

PMID- 25974872
TI  - Clinical cardiac structural anatomy reconstructed within the cardiac contour
      using multidetector-row computed tomography: Left ventricular outflow tract.
AB  - The left ventricular outflow tract (LVOT) is a common site of idiopathic
      ventricular arrhythmia. Many electrocardiographic characteristics for predicting
      the origin of arrhythmia have been reported, and their prediction rates are
      clinically acceptable. Because these approaches are inductive, based on QRS-wave
      morphology during the arrhythmia and endocardial or epicardial pacing, three
      dimensional anatomical accuracy in identifying the exact site of the catheter
      position is essential. However, fluoroscopic recognition and definition of the
      anatomy around the LVOT can vary among operators, and three-dimensional
      anatomical recognition within the cardiac contour is difficult because of the
      morphological complexity of the LVOT. Detailed knowledge about the three
      dimensional fluoroscopic cardiac structural anatomy could help to reduce the need
      for contrast medium injection and radiation exposure, and to perform safe
      interventions. In this article, we present a series of structural images of the
      LVOT reconstructed in combination with the cardiac contour using multidetector
      row computed tomography. We also discuss the clinical implications of these
      findings based on the accumulated insights of research pioneers.

PMID- 25974871
TI  - Detection of minimal residual disease in B lymphoblastic leukemia using viSNE.
AB  - BACKGROUND: Minimal residual disease (MRD) following treatment is a robust
      prognostic marker in B lymphoblastic leukemia. However, the detection of MRD by
      flow cytometric immunophenotyping is technically challenging, and an automated
      method to detect MRD is therefore desirable. viSNE, a recently developed
      computational tool based on the t-Distributed Stochastic Neighbor Embedding (t
      SNE) algorithm, has been shown to be capable of detecting synthetic "MRD-like"
      populations of leukemic cells created in vitro, but whether viSNE can facilitate
      the immunophenotypic detection of MRD in clinical samples has not been evaluated.
      METHODS: We applied viSNE retrospectively to 8-color flow cytometric
      immunophenotyping data from normal bone marrow samples, and samples from B
      lymphoblastic leukemia patients with or without suspected MRD on the basis of
      conventional manual gating. RESULTS: In each of 14 bone marrow specimens
      containing MRD or suspected MRD, viSNE identified a putative MRD population; an
      abnormal composite immunophenotype was confirmed for the putative MRD in each
      case. MRD populations were not identified by viSNE in control bone marrow samples
      from patients with increased normal B-cell precursors, or in post-treatment
      samples from B lymphoblastic leukemia patients who did not have detectable MRD by
      manual gating. CONCLUSION: viSNE shows promise as an automated method to
      facilitate immunophenotypic MRD detection in patients treated for B lymphoblastic
      leukemia.

PMID- 25974873
TI  - Is gamma loop dysfunction related to bilateral inhibition in anterior knee pain?
AB  - INTRODUCTION: The potential relationship between bilateral quadriceps inhibition
      in individuals with unilateral anterior knee pain (AKP) and gamma loop
      dysfunction is examined in this study. METHODS: Twelve individuals with
      unilateral AKP and 10 healthy controls were recruited. Quadriceps voluntary
      activation (%VA) was quantified using a triggered interpolated twitch technique.
      Gamma loop function was assessed through knee extension maximum voluntary
      isometric contractions before and after 20 minutes of 50-Hz patellar tendon
      vibration. RESULTS: The AKP group exhibited 5.7% lower %VA bilaterally compared
      with controls (P = 0.039, Cohen d = 0.79). After prolonged vibration, both groups
      exhibited an average 8.5% reduction in knee extension force in each limb (P <
      0.001, Cohen d = 0.85). CONCLUSIONS: Significant force reductions after vibration
      suggest that gamma loop dysfunction was not seen in either control or AKP
      participants. Bilateral quadriceps inhibition in the AKP group does not appear to
      be associated with gamma loop dysfunction.

PMID- 25974875
TI  - Lip Forces and Chewing Efficiency in Children with Peripheral Facial Paralysis.
AB  - Peripheral facial paralysis is accompanied by facial motor disorders and also, by
      oral dysfunctions. The aim of this study was to evaluate the lip forces and
      chewing efficiency in a group of children with peripheral facial paralysis. The
      degree of peripheral facial paralysis in the study group (n 11) was assessed
      using the House-Brackmann scale. The control group consisted of 21 children
      without facial nerve impairment. To assess lip forces, acrylic vestibular plates
      of three sizes were used: large (LVP), medium (MVP) and small (SVP). The lip
      force was recorded with a force transducer coupled with the data acquisition
      system. Masticatory efficiency was evaluated by the ability to mix two
      differently colored chewing gums. The images were processed with Adobe Photoshop
      CS3 (Delaware Corporation, San Jose, California, United States) and the number of
      pixels was quantified with the Image J software (DHHS/NIH/NIMH/RSB, Maryland,
      United States). For statistical analysis, the following statistical analysis were
      used: Pearson or Spearman correlation coefficient, multiple linear regression
      analysis, multiple logistic regression analysis, and optimal cutoff values for
      muscular dysfunction. There were statistically significant differences between
      lip forces in the following three groups: p=0.01 (LVP), p=0.01 (MVP), and p=0.008
      (SVP). The cutoff values of lip forces in the study group were as follows: 7.08 N
      (LVP), 4.89 N (MVP), and 4.24 N (SVP). There were no statistically significant
      differences between the masticatory efficiency in the two groups (p=0.25). Lip
      forces were dependent on the degree of peripheral facial paralysis and age, but
      not on gender. In peripheral facial paralysis in children, a significant decrease
      of lip forces, but not masticatory efficiency, occurs.

PMID- 25974874
TI  - Body image and sexual function in women after treatment for anal and rectal
      cancer.
AB  - OBJECTIVE: Treatment for anal and rectal cancer (ARCa) often results in side
      effects that directly impact sexual functioning; however, ARCa survivors are an
      understudied group, and factors contributing to the sexual sequelae are not well
      understood. Body image problems are distressing and may further exacerbate sexual
      difficulties, particularly for women. This preliminary study sought to (1)
      describe body image problems, including sociodemographic and disease/treatment
      correlates, and (2) examine relations between body image and sexual function.
      METHODS: For the baseline assessment of a larger study, 70 women completed the
      European Organization for Research and Treatment of Cancer Core Quality of Life
      Questionnaire and Colorectal Cancer-specific Module, including the Body Image
      subscale, and Female Sexual Function Index. Pearson's correlation and multiple
      regression evaluated correlates of body image. Among sexually active women (n =
      41), hierarchical regression examined relations between body image and sexual
      function domains. RESULTS: Women were on average 55 years old (standard deviation
      = 11.6), non-Hispanic White (79%), married (57%), and employed (47%). The
      majority (86%) reported at least one body image problem. Younger age, lower
      global health status, and greater severity of symptoms related to poorer body
      image (p's < 0.05). Poor body image was inversely related to all aspects of
      sexual function (beta range 0.50-0.70, p's < 0.05), except pain. The strongest
      association was with Female Sexual Function Index Sexual/Relationship
      Satisfaction. CONCLUSION: These preliminary findings suggest the importance of
      assessing body image as a potentially modifiable target to address sexual
      difficulties in this understudied group. Further longitudinal research is needed
      to inform the development and implementation of effective interventions to
      improve the sexual health and well-being of female ARCa survivors.

PMID- 25974876
TI  - Clinical and Neuroimaging Features in Two Children with Mutations in the
      Mitochondrial ND5 Gene.
AB  - Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide
      dehydrogenase 5 gene (MT-ND5) has been implicated as an important genetic cause
      of childhood mitochondrial encephalomyopathies. This study reports the clinical
      and magnetic resonance imaging findings in two pediatric patients with mutations
      in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G>A
      mutation presented with infantile basal ganglia stroke syndrome secondary to
      mineralizing angiopathy. The 7-year-old girl with the m.13514A>G mutation had
      episodic regression, progressive ataxia, optic atrophy, and hyperactivity.
      Magnetic resonance imaging of the brain showed bilateral symmetrical signal
      intensity changes in the thalamus, tectal plate, and inferior olivary nucleus,
      which subsided on follow-up image. Both the patients had a stable course.
      Familiarity with the various phenotypic and magnetic resonance imaging findings
      and the clinical course in childhood mitochondrial encephalomyopathies may help
      the physician in targeted metabolic-genetic testing and prognostication.

PMID- 25974877
TI  - Enhanced and durable protective immune responses induced by a cocktail of
      recombinant BCG strains expressing antigens of multistage of Mycobacterium
      tuberculosis.
AB  - Although Bacillus Calmette-Guerin (BCG) vaccine confers protection from
      Mycobacterium tuberculosis infection in children, its immune protection gradually
      wanes over time, and consequently leads to an inability to prevent the
      reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for
      better control of tuberculosis (TB) is urgently needed. We thus hypothesized that
      recombinant BCG overexpressing immunodominant antigens expressed at different
      growth stages of M. tuberculosis could provide a more comprehensive protection
      against primary and latent M. tuberculosis infection. Here, a novel cocktail of
      recombinant BCG (rBCG) strains, namely ABX, was produced by combining rBCG::85A,
      rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A,
      Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to
      induce a stronger immune protection than individual rBCGs or BCG against primary
      TB infection in C57BL/6 mice. Mechanistically, the immune protection was
      attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of
      IFN-gamma(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These
      findings thus provide a novel strategy for the improvement of BCG efficacy and
      potentially a promising prophylactic TB vaccine candidate, warranting further
      investigation.

PMID- 25974878
TI  - IL-15-secreting gammadeltaT cells induce memory T cells in experimental allergic
      encephalomyelitis (EAE) mice.
AB  - With the most recent data suggesting gammadeltaT cells as primary producers of
      the pro-inflammatory autoimmune-associated cytokine, the relationship between
      gammadeltaT cells and Th17 in experimental allergic encephalitis (EAE) mice
      requires more extensive investigation. By flow cytometry and qPCR, we identified
      a new subset of IL-15-secreting gammadeltaT (gammadeltaT15) cells that increased
      in EAE mice. The capacity of IL-15-secreting gammadeltaT cells inducing memory T
      cells and memory T cells inducing IL-17(+)Th17 was examined by transferring into
      EAE mice and 7-week-old female nude mice, respectively. We found that
      gammadeltaT15 induced CD44(hi) memory T cells by secreting IL-15. gammadeltaT15
      induced memory T cells induced EAE by transforming into pathogenic Th17 cells.
      The data suggest that a new subset of IL-15-secreting gammadeltaT cells mediated
      the production of memory T cells which transformed into pathogenic Th17 cells in
      EAE mice.

PMID- 25974880
TI  - Novel sample preparation for operando TEM of catalysts.
AB  - A new TEM sample preparation method is developed to facilitate operando TEM of
      gas phase catalysis. A porous Pyrex-fiber pellet TEM sample was produced,
      allowing a comparatively large amount of catalyst to be loaded into a standard
      Gatan furnace-type tantalum heating holder. The increased amount of catalyst
      present inside the environmental TEM allows quantitative determination of the gas
      phase products of a catalytic reaction performed in-situ at elevated
      temperatures. The product gas concentration was monitored using both electron
      energy loss spectroscopy (EELS) and residual gas analysis (RGA). Imaging of
      catalyst particles dispersed over the pellet at atomic resolution is challenging,
      due to charging of the insulating glass fibers. To overcome this limitation, a
      metal grid is placed into the holder in addition to the pellet, allowing catalyst
      particles dispersed over the grid to be imaged, while particles in the pellet,
      which are assumed to experience identical conditions, contribute to the overall
      catalytic conversion inside the environmental TEM cell. The gas within the cell
      is determined to be well-mixed, making this assumption reasonable. 

PMID- 25974879
TI  - Synthesis and Applications of Hajos-Parrish Ketone Isomers.
AB  - Numerous natural products possess ring systems and functionality for which Hajos
      Parrish ketone isomers with a transposed methyl group (termed "iso-Hajos-Parrish
      ketones") would be of value. However, such building blocks have not been
      exploited to the same degree as the more typical Hajos-Parrish hydrindane. An
      efficient three-step synthesis of such materials was fueled by a simple method
      for the rapid preparation of highly functionalized cyclopentenones, several of
      which are new chemical entities that would be challenging to access through other
      approaches. Furthermore, one iso-Hajos-Parrish ketone was converted into two
      distinct natural product analogues and one natural product. As one indication of
      the value of these new building blocks, that latter target was obtained in 10
      steps, having previously been accessed in 18 steps using the Hajos-Parrish
      ketone. 

PMID- 25974881
TI  - Double-tilt in situ TEM holder with multiple electrical contacts and its
      application in MEMS-based mechanical testing of nanomaterials.
AB  - MEMS and other lab-on-a-chip systems are emerging as attractive alternatives to
      carry out experiments in situ the electron microscope. However, several
      electrical connections are usually required for operating these setups. Such
      connectivity is challenging inside the limited space of the TEM side-entry
      holder. Here, we design, implement and demonstrate a double-tilt TEM holder with
      capabilities for up to 9 electrical connections, operating in a high-resolution
      TEM. We describe the operating principle of the tilting and connection mechanisms
      and the physical implementation of the holder. To demonstrate the holder
      capabilities, we calibrate the tilting action, which has limits of +/-15 degrees
      , and establish the insulation resistance of the electronics to be 36GOmega,
      appropriate for measurements of currents down to the nano-amp (nA) regime.
      Furthermore, we demonstrate tensile testing of silver nanowires using a
      previously developed MEMS device for mechanical testing, using the implemented
      holder as the platform for electronic operation and sensing. The implemented
      holder can potentially have broad application to other areas where MEMS or
      electrically-actuated setups are used to carry out in situ TEM experiments. 

PMID- 25974882
TI  - Using transmission Kikuchi diffraction to study intergranular stress corrosion
      cracking in type 316 stainless steels.
AB  - Transmission Kikuchi diffraction (TKD), also known as transmission-electron
      backscatter diffraction (t-EBSD) is a novel method for orientation mapping of
      electron transparent transmission electron microscopy specimen in the scanning
      electron microscope and has been utilized for stress corrosion cracking
      characterization of type 316 stainless steels. The main advantage of TKD is a
      significantly higher spatial resolution compared to the conventional EBSD due to
      the smaller interaction volume of the incident beam with the specimen. Two 316
      stainless steel specimen, tested for stress corrosion cracking in hydrogenated
      and oxygenated pressurized water reactor chemistry, were characterized via TKD.
      The results include inverse pole figure (IPFZ) maps, image quality maps and
      misorientation maps, all acquired in very short time (<60 min) and with
      remarkable spatial resolution (up to 5 nm step size possible). They have been
      used in order to determine the location of the open crack with respect to the
      grain boundary, deformation bands, twinning and slip. Furthermore, TKD has been
      used to measure the grain boundary misorientation and establish a gauge for
      quantifying plastic deformation at the crack tip and other regions in the
      surrounding matrix. Both grain boundary migration and slip transfer have been
      detected as well.

PMID- 25974890
TI  - Selective Cell Adhesion and Biosensing Applications of Bio-Active Block
      Copolymers Prepared by CuAAC/Thiol-ene Double Click Reactions.
AB  - N-Acetyl-l-cysteine (NAC)-capped poly(methyl methacrylate)-b-polycaprolactone
      block copolymer (PMMA-b-PCL-NAC) was prepared using the previously described one
      pot photoinduced sequential CuAAC/thiol-ene double click procedure. PMMA-b-PCL
      NAC had previously shown good applicability as a matrix for cell adhesion of
      cells from the Vero cell line (African green monkey kidney epithelial). Here, in
      this work, PMMA-b-PCL-NAC served as an excellent immobilization matrix for
      biomolecule conjugation. Covalent binding of RGD (R: arginine, G: glycine, and D:
      aspartic acid) peptide sequence onto the PMMA-b-PCL-NAC-coated surface was
      performed via EDC chemistry. RGD-modified PMMA-b-PCL-NAC (PMMA-b-PCL-NAC-RGD) as
      a non-toxic cell proliferation platform was used for selective "integrin
      alphavbeta3-mediated cell adhesion and biosensing studies. Both optical and
      electrochemical techniques were used to monitor the adhesion differences between
      "integrin alphavbeta3" receptor positive and negative cell lines on to the
      designed biofunctional surfaces. 

PMID- 25974891
TI  - Tetramethoxybenzene is a Good Building Block for Molecular Wires: Insights from
      Photoinduced Electron Transfer.
AB  - Two donor bridge-acceptor molecules with terminal triarylamine and Ru(bpy)3(2+)
      (bpy = 2,2'-bipyridine) redox partners were synthesized and investigated by
      cyclic voltammetry, optical absorption, luminescence, and transient absorption
      spectroscopy. The two dyads differ only by the central bridging unit, which was
      tetramethoxybenzene (tmb) in one case and unsubstituted phenylene (ph) in the
      other case. Photoirradiation of the Ru(bpy)3(2+) complex of the two dyads
      triggers intramolecular electron transfer from the triarylamine to the (3)MLCT
      excited metal complex, and this process occurs with time constants of 1.5 and 6.8
      ns for the tmb- and ph-bridged dyads, respectively. Thermal electron transfer in
      the reverse direction then leads to disappearance of the photoproduct with a time
      constant of 10 ns in both dyads. The faster rate of photoinduced charge transfer
      in the tmb-bridged dyad can be understood in the framework of a hole-tunneling
      model in which the electron-rich tmb bridge imposes a more shallow barrier than
      the less electron-rich ph spacer. Until now tmb-based molecular wires have
      received very little attention, and alkoxy substituents have been mostly used for
      improving the solubility of oligo-p-phenylene vinylene (OPV) and oligo-p
      phenylene ethynylene (OPE) wires. Our study illustrates how four alkoxy
      substituents on a phenylene backbone can have a significant influence on the
      charge-transfer properties of a molecular wire, and this is relevant in the
      greater context of a future molecular electronics technology. 

PMID- 25974894
TI  - The technological future of 7 T MRI hardware.
AB  - In this article we present our projections of future hardware developments on 7 T
      human MRI systems. These include compact cryogen-light magnets, improved gradient
      performance, integrated RF-receive and direct current shimming coil arrays, new
      RF technology with adaptive impedance matching, patient-specific specific
      absorption rate estimation and monitoring, and increased integration of
      physiological monitoring systems. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25974895
TI  - Liver fibrosis. Foreword.

PMID- 25974896
TI  - Origin and function of myofibroblasts in the liver.
AB  - Liver fibrosis contributes to many of the devastating complications of viral,
      toxic, fatty, and cholestatic liver disease. Understanding the cell populations
      that promote liver fibrosis and the molecular pathways through which they operate
      is essential for the development of antifibrotic therapies. The authors review
      the origins and functions of hepatic myofibroblasts, focusing on hepatic stellate
      cells, the main contributors to organ fibrosis, and portal fibroblasts, an
      insufficiently characterized population that may have a specialized function in
      promoting periductular fibrosis, but a limited role in overall organ fibrosis.
      They discuss the hypothesis that each fibrogenic cell population in the liver
      exerts specific functions, and whether cell type-specific antifibrotic strategies
      are required or whether one therapeutic strategy fits all. 

PMID- 25974897
TI  - Emerging and disease-specific mechanisms of hepatic stellate cell activation.
AB  - The last decade has seen a rapid expansion in our understanding of the mechanisms
      leading to hepatic stellate cell activation. The classic activation pathway of
      initiation, perpetuation and regression remains as a useful model; however, the
      emergence of several new pathways and mediators has revealed a deeper complexity
      than previously appreciated. Although core fibrogenic pathways exist across
      organs and disease types, there is accumulating evidence for disease- and context
      specific mechanisms that may modulate or drive hepatic fibrogenesis. Hence, a
      "one size fits all" approach to antifibrotic therapy may not be appropriate for
      all disease settings. The authors present a focused and concise update of the
      most recent advances in our understanding of hepatic stellate cell activation
      pathways, while highlighting several challenges that may be constraining
      progress. This summary provides a foundation to further expand our knowledge of
      this unique cell type and its contributions to human liver disease. 

PMID- 25974898
TI  - Resolution of liver fibrosis: basic mechanisms and clinical relevance.
AB  - With evidence from a large number of animal models and clinical trials, it is now
      beyond debate that liver fibrosis and even cirrhosis are potentially reversible
      if the underlying cause can be successfully eliminated. However, in a significant
      proportion of patients cure of the underlying disease may not result in fibrosis
      regression or a significant reduction of the risk for hepatocellular carcinoma
      development. Understanding of the mechanistic pathways and regulatory factors
      that characterize matrix remodeling and architectural repair during fibrosis
      regression may provide therapeutic approaches to induce or accelerate regression
      as well as novel diagnostic tools. Recent seminal observations have determined
      that in resolving liver fibrosis a significant proportion of hepatic stellate
      cell-myofibroblasts (HSC-MFs) can revert to a near quiescent phenotype. Hepatic
      macrophages derived from inflammatory monocytes may contribute to fibrosis
      resolution through an in situ phenotypic switch mediated by phagocytosis.
      Emerging therapeutic approaches include deletion or inactivation of HSC-MFs,
      modulation of macrophage activity and autologous cell infusion therapies. Novel
      noninvasive diagnostic tests such as serum and imaging markers responsive to
      extracellular matrix degradation are being developed to evaluate the clinical
      efficacy of antifibrotic interventions. 

PMID- 25974899
TI  - Fibrosis in nonalcoholic Fatty liver disease: mechanisms and clinical
      implications.
AB  - Nonalcoholic fatty liver disease (NAFLD) is tightly associated with obesity and
      the metabolic syndrome in the United States and other Western countries. It is
      also the liver disease most rapidly increasing in prevalence in the United
      States, and has become a major indication for liver transplantation worldwide.
      Compelling evidence shows that the degree of liver fibrosis dictates liver
      prognosis in NAFLD. This review focuses on fibrosis based on clinical and basic
      perspectives. The authors summarize the physiopathology of fibrosis development
      and progression in NAFLD, highlighting its molecular mechanisms, clinical
      consequences of fibrosis, the diagnostic approach and management strategies. 

PMID- 25974900
TI  - Liver fibrosis in alcoholic liver disease.
AB  - Excessive alcohol consumption causes a wide spectrum of liver disease, ranging
      from simple steatosis to severe forms of liver injury such as steatohepatitis,
      liver fibrosis, cirrhosis, and liver cancer. Moreover, alcohol consumption also
      accelerates liver fibrosis in patients with other types of liver diseases such as
      viral hepatitis and nonalcoholic fatty liver disease. Virtually all clinical
      complications of alcoholic liver disease occur in patients with established
      fibrosis and cirrhosis, thus making fibrosis a key parameter for treatment and
      prognosis of patients. Here, the authors review diagnosis, management, and
      antifibrotic therapy of alcoholic liver fibrosis. They discuss both the unique
      features of alcoholic liver fibrosis and the similarities to liver fibrosis from
      other etiologies, and review molecular pathogenesis and animal models. Finally,
      future directions for basic and clinical research on alcoholic liver fibrosis are
      proposed. 

PMID- 25974901
TI  - Liver Fibrosis in the Post-HCV Era.
AB  - The introduction of interferon-free regimens for the treatment of chronic
      hepatitis C virus (HCV) infection represents a key turn in hepatology because of
      their extremely high therapeutic efficacy and relatively safe use also in
      "difficult-to-treat" and/or "difficult-to-cure" HCV subgroups, including patients
      with cirrhosis. Due to treatment guidelines based on health economics, patients
      with cirrhosis will likely represent the frontline in the use of the new anti-HCV
      agents. Accordingly, this article concentrates on the effect of sustained viral
      response (SVR) following antiviral treatment for HCV on the evolution of tissue
      fibrosis and cirrhosis, and more importantly, on the clinical consequences of
      viral eradication, particularly in patients in which SVR has been achieved in an
      advanced stage of the disease. In this context, the assessment of fibrosis
      regression and possibly of cirrhosis reversal will represent the diagnostic
      challenge of the next decade. 

PMID- 25974902
TI  - Diagnosis of liver fibrosis: present and future.
AB  - The diagnostic assessment of liver fibrosis, a major determinant of disease
      severity, is an important step in the management of patients with chronic liver
      diseases. Liver biopsy is still considered the gold standard for the assessment
      of necroinflammation and fibrosis; however, recent technical advances have
      resulted in the development of numerous serum biomarkers and imaging tools as
      noninvasive alternatives to biopsy. These tests include biological (serum
      biomarker algorithms), physical (imaging assessment of tissue stiffness), and
      physiological (breath test) methods. Accumulating evidence shows that noninvasive
      tests provide prognostic information of clinical relevance, which has led to
      their incorporation into clinical guidelines and everyday practice. Here, the
      authors review and compare invasive and noninvasive tests for the diagnosis of
      liver fibrosis. They discuss emerging functional genomic, microparticle, protein
      profiling, and bioimaging tools, focusing on novel sensitive tools that are able
      to assess the dynamic nature of fibrogenesis, a key requirement for the
      assessment of the efficacy of antifibrotic compounds in the future. 

PMID- 25974904
TI  - Regression of steatohepatitis-related cirrhosis.
AB  - The authors document regression of cirrhosis in an obese 56-year-old man after
      significant weight loss by sequential liver biopsies. The patient had a known
      history of steatohepatitis. His initial laboratory workup 6 years earlier
      revealed elevated liver enzyme activities and blood triglyceride levels, and
      negative viral hepatitis serology screen. A liver biopsy at that time showed
      histological features consistent with precirrhotic stage of active
      steatohepatitis. A liver biopsy performed 4 years later revealed progression of
      the disease to cirrhosis. Following this diagnosis he went on a special strict
      diet and lost 49 kg. His body mass index decreased from 46 to 28 during a 2-year
      period and his liver enzyme activities returned to normal. A liver biopsy at this
      time demonstrated significant regression of the liver fibrosis and disappearance
      of the steatosis and necroinflammation. In conclusion, massive weight loss
      resulted in resolution of liver fibrosis in this obese patient with
      steatohepatitis-related cirrhosis. 

PMID- 25974905
TI  - Development of photocatalysts for selective and efficient organic
      transformations.
AB  - One of the main goals of organic chemists is to find easy, environmentally
      friendly, and cost effective methods for the synthesis of industrially important
      compounds. Photocatalysts have brought revolution in this regard as they make use
      of unlimited source of energy (the solar light) to carry out the synthesis of
      organic compounds having otherwise complex synthetic procedures. However,
      selectivity of the products has been a major issue since the beginning of
      photocatalysis. The present article encompasses state of the art accomplishments
      in harvesting light energy for selective organic transformations using
      photocatalysts. Several approaches for the development of photocatalysts for
      selective organic conversions have been critically discussed with the objective
      of developing efficient, selective, environmental friendly and high yield
      photocatalytic methodologies. 

PMID- 25974906
TI  - Natural dye sensitized TiO2 nanorods assembly of broccoli shape based solar
      cells.
AB  - TiO2 nanorods based thin films with rutile phase have been synthesized using
      template free low temperature hydrothermal method. The scanning electron
      microscope images showed that the prepared TiO2 samples were made of TiO2
      nanorods and the nanorods had arranged by itself to form a broccoli like shape.
      The X-ray diffraction studies revealed that the prepared TiO2 samples exhibit
      rutile phase. The grown TiO2 nanorods had been sensitized using the flowers of
      Sesbania (S) grandiflora, leaves of Camellia (C) sinensis and roots of Rubia (R)
      tinctorum. Dye sensitized solar cells had been fabricated using the natural dye
      sensitized TiO2 nanorods based thin film photoelectrode and the open circuit
      voltage and short circuit current density were found to lie in the range of 0.45
      0.6 V and 5.6-6.4 mA/cm(2) respectively. The photovoltaic performance of all the
      fabricated natural dye sensitized TiO2 solar cells indicate that natural dyes
      have the potential to be used as effective sensitizer in dye sensitized solar
      cells.

PMID- 25974907
TI  - A comparative study of cytotoxicity and interaction with DNA/protein of five
      transition metal complexes with Schiff base ligands.
AB  - Five transition metal complexes NiL(1)2 (1), CuL(1)2 (2), ZnL(1)2 (3),
      [MnL(1)2(N3)]n.nCH2Cl2 (4), CuL(2)2 (5) {HL(1)=3-{[2-(2-hydroxy-ethoxy)
      ethylimino]-methyl}-naphthalen-2-ol, HL(2)=2-{[2-(2-hydroxy-ethoxy)-ethylimino]
      methyl}-phenol} have been synthesized and fully characterized. In all of the
      complexes, the ligands coordinated to the metal ion in a negative fashion via O
      and N donor atoms. The X-ray structures of nickel complex 1 and copper complexes
      2 and 5 are four-coordinated monomers and show slightly distorted square-planar
      geometry in the vicinity of the central metal atom. Zinc complex 3 exhibits a
      four-coordinated tetrahedral structure. Differently, manganese complex 4 reveals
      a six-coordinated octahedral structure, one-dimensional chain is linked by azide
      in the end-to-end mode. In vitro cytotoxicity of these complexes to various tumor
      cell lines was assayed by the MTT method. The results showed that most of these
      metal-Schiff base complexes exhibited enhanced cytotoxicity than Schiff base
      ligands, which clearly implied a positive synergistic effect. Moreover, these
      complexes appeared to be selectively active against certain cell lines. The
      interactions of these metal complexes with CT-DNA were investigated by UV-vis,
      fluorescence and CD spectroscopy, the results indicated that these complexes are
      metallointercalators and can interact with CT-DNA. The study of interaction
      between complexes and BSA indicated that all of the complexes could quench the
      intrinsic fluorescence of BSA in a static quenching process.

PMID- 25974908
TI  - Changing the calculus of pediatric product development: narrowing the too-big gap
      between need and solution in a small market.
AB  - First, Deliece Hofen drops the pill into hot water to soften the outside coating.
      Then, she slices through the center of the pill with an X-ACTO knife and squeezes
      the isotretinoin inside into a syringe. With the drug in liquid form, she can now
      administer it to her ten-year-old son Brandon. ?The problem is...some of [the
      isotretinoin] is still left inside of the capsule and I?m not getting an exact
      dosage,? admits Hofen. 

PMID- 25974909
TI  - The heart of the matter: from guided microtools to 3-D printing and precision
      genome editing, promising research could lead to new advances in pediatric
      cardiology.
AB  - The smooth, powerful muscles of a newborn baby?s heart are pulsing normally,
      squeezing in and letting go rhythmically as a 3-mm-wide catheter-like tube snakes
      its way through, entering via an artery and being guided slowly by a surgeon.
      When it reaches its target?a protruding knot of malformed muscle tissue within a
      ventricle that has been partly blocking the valve?the tip of the precisely
      controlled tube whirs into action, with tiny scissor-like rotating blades gently
      grinding up the excess tissue as those pieces are sucked back into the device,
      leaving no floating particles that could lead to a blockage elsewhere. The defect
      is fully removed, and the heart?s function is restored to normal, leaving the
      child with the prospect of a normal life. The whole minimally invasive process
      takes place inside a beating heart and would otherwise have required open-heart
      surgery, with the heart stopped for a cardiopulmonary bypass. 

PMID- 25974903
TI  - Antifibrotic therapies in the liver.
AB  - Significant progress has been made in understanding the principles underlying the
      development of liver fibrosis. This includes appreciating its dynamic nature, the
      importance of active fibrolysis in fibrosis regression, and the plasticity of
      cell populations endowing them with fibrogenic or fibrolytic properties. This is
      complemented by an increasing array of therapeutic targets with known roles in
      the progression or regression of fibrosis. With a key role for fibrosis in
      determining clinical outcomes and encouraging data from recently Food and Drug
      Administration-approved antifibrotics for pulmonary fibrosis, the development and
      validation of antifibrotic therapies has taken center stage in translational
      hepatology. In addition to summarizing the recent progress in antifibrotic
      therapies, the authors discuss some of the challenges ahead, such as achieving a
      better understanding of the interindividual heterogeneity of the fibrotic
      response, how to match interventions with the ideal patient population, and the
      development of better noninvasive methods to assess the dynamics of fibrogenesis
      and fibrolysis. Together, these advances will permit a better targeting and dose
      titration of individualized therapies. Finally, the authors discuss combination
      therapy with different antifibrotics as possibly the most potent approach for
      treating fibrosis in the liver. 

PMID- 25974910
TI  - Harnessing online tools to track-and treat-pediatric illness: new tools are
      giving researchers, physicians, and child-care centers insight into the spread of
      disease.
AB  - Measles. A strange polio-like paralysis. Ebola. In the last year, the spread of
      infectious disease has become standard fare for the nightly news. As such
      diseases grab headlines, child-care providers, families, schools, and public
      health officials are turning to new ways of understanding and coping with the
      spread of disease. 

PMID- 25974911
TI  - Retro reproduction: an old imaging technology rewrites the rules of modern
      embryology.
AB  - On a video screen, against a black backdrop, 15 spherical blue-green cells
      vibrate with a quiet energy. Slowly at first, then faster, they begin to roil and
      roll. Within the confines of their round membrane cases, they divide, becoming
      two, three, four cells, then those, in turn, divide to become eight. One splits
      into two, then pauses, struggling to catch up and spinning off pieces of cellular
      detritus as it does. Near the top, another, by now many cells rich, hollows out
      and expands, contracts, expands, contracts. It falls in upon itself and then
      hatches, pouring out from its shell and ballooning to the side. 

PMID- 25974912
TI  - Light plus sound: combination technology delivers a one-two punch to disease.
AB  - In just a decade, optoacoustic or photoacoustic imaging has become one of the
      fastest growing areas of biomedical technology, exploding from just a handful of
      research groups in the late 1990s to more than 400 dedicated scientists and
      engineers today. Much of the expansion has come since researchers started pairing
      optoacoustics with the already-existing technology of medical ultrasound and
      envisioning how it could easily step into the clinic to fight a diversity of
      diseases. 

PMID- 25974913
TI  - Photoacoustic microscopy: superdepth, superresolution, and superb contrast.
AB  - Since its invention in the 17th century, optical microscopy has revolutionized
      biomedical studies by scrutinizing the biological realm on cellular levels,
      taking advantage of its excellent light-focusing capability. However, most
      biological tissues scatter light highly. As light travels in tissue, cumulative
      scattering events cause the photons to lose their original propagation direction
      and, thus, their ability to be focused, which has largely limited the penetration
      depth of optical microscopy. Conventional planar optical microscopy can provide
      penetration of only ~100 ?m before photons begin to be scattered. The penetration
      of modern optical microcopy, such as confocal microscopy and multiphoton
      microscopy, is still limited to approximately the optical diffusion limit (~1 mm
      in the skin as approximated by one optical transport mean free path), where
      scattered photons retain a strong memory of the original propagation direction.
      So far, it still remains a challenge for pure optical methods to achieve high
      resolution in vivo imaging beyond the diffusion limit (i.e., superdepth imaging).

PMID- 25974914
TI  - Looking deeper: multimodal and contrast-enhanced photoacoustic imaging offer a
      clearer view within tissues for more accurate diagnosis.
AB  - Optical imaging modalities such as fluorescence (FL) microscopy, multiphoton
      microscopy, and optical coherence tomography (OCT) have been well established for
      high optical contrast and high spatial resolution imaging of biological tissues.
      However, as they are dependent on ballistic photons, these methods fail to image
      beyond ~1 mm or so inside biological tissue. In contrast, diffuse optical imaging
      (DOI), which uses multiple scattered photons for imaging, can image much deeper
      (up to a several centimeters) into the tissue. Unfortunately, due to strong light
      scattering in tissues, it fails to maintain the high resolution at the deeper
      imaging depth. Photoacoustic imaging (PAI) bridges this gap of imaging deeper
      with high resolution and contrast by combining optical excitation with acoustic
      detection [1]. 

PMID- 25974915
TI  - Clinical photoacoustic breast imaging: the Twente experience.
AB  - Globally, breast cancer is the most frequently occurring malignancy in women and
      the leading cause of cancer deaths, with up to half a million women dying of the
      disease in 2008. Early detection and accurate diagnosis of breast cancer is
      crucial for optimizing survival chances, with imaging technologies playing a
      major role. X-ray mammography (XRM) and ultrasound (US) imaging, however, suffer
      from nonoptimal sensitivity and specificity. Furthermore, X-ray mammography uses
      ionizing radiation and painful breast compression and has poor performance in
      dense breasts. For US imaging, interoperator dependence and poor soft tissue
      contrast are drawbacks. 

PMID- 25974916
TI  - Extending biological imaging to the fifth dimension: evolution of volumetric
      small animal multispectral optoacoustic tomography.
AB  - Despite the ancient discovery of the basic physical phenomenon underlying
      optoacoustic imaging and tomography [1], the lack of suitable laser sources,
      ultrasound detection technology, data acquisition, and processing capacities has
      long hindered the realization of efficient imaging devices. In fact, the first
      high-quality images from living animals were obtained about a decade ago (Figure
      1), which was followed by an exponential growth of technical developments in
      instrumentation, algorithms, and biomedical applications surrounding this
      fascinating field. The ability of optoacoustics to probe optical contrast along a
      wide domain of penetration scales while maintaining excellent spatiotemporal
      resolution representative of ultrasound imaging, as shown in Figure 2, is
      unparalleled among the other optical imaging modalities [2], [3]. 

PMID- 25974917
TI  - A simulation study on the quantitative assessment of tissue microstructure with
      photoacoustics.
AB  - A detailed derivation of a quantity, defined as the acoustic power per unit solid
      angle far from the illuminated volume divided by the intensity of the incident
      light beam and termed as differential photoacoustic (PA) cross section, is
      presented. The expression for the differential PA cross section per unit
      absorbing volume retains two terms, namely, the coherent and the incoherent
      parts. The second part based on a correlation model can be employed to analyze
      the PA signal power spectrum for tissue characterization. The performances of the
      fluid sphere, Gaussian, and exponential correlation models in assessing the mean
      size and the variance in the optical absorption coefficients of absorbers were
      investigated by performing in silico experiments. It was possible to evaluate
      diameters of solid spherical absorbers with radii >= 20 MUm with an accuracy of
      10% for an analysis bandwidth of 5 to 50 MHz using the first two correlation
      models. The accuracy of estimation was about 22% for fluid spheres mimicking
      erythrocytes for the third correlation model for an analysis bandwidth of 5 to
      100 MHz. The extracted values of average variance in the optical absorption
      coefficients demonstrated good correlation with the nominal values. This study
      suggests that the method presented here may be developed as a potential tissue
      characterization tool. 

PMID- 25974918
TI  - 3-D imaging using row-column-addressed arrays with integrated apodization - part
      i: apodization design and line element beamforming.
AB  - This paper investigates the effect of transducerintegrated apodization in row
      column-addressed arrays and presents a beamforming approach specific for such
      arrays. Row-column addressing 2-D arrays greatly reduces the number of active
      channels needed to acquire a 3-D volume. A disadvantage of row-column-addressed
      arrays is an apparent ghost effect in the point spread function caused by edge
      waves. This paper investigates the origin of the edge waves and the effect of
      introducing an integrated apodization to reduce the ghost echoes. The performance
      of a lambda/2-pitch 5-MHz 128 + 128 row-column-addressed array with different
      apodizations is simulated. A Hann apodization is shown to decrease imaging
      performance away from the center axis of the array because of a decrease in main
      lobe amplitude. Instead, a static roll-off apodization region located at the ends
      of the line elements is proposed. In simulations, the peak ghost echo intensity
      of a scatterer at (x,y, z) = (8, 3, 30) mm was decreased by 43 dB by integrating
      roll-off apodization into the array. The main lobe was unaffected by the
      apodization. Simulations of a 3-mm-diameter anechoic blood vessel at 30 mm depth
      showed that applying the transducer-integrated apodization increased the apparent
      diameter of the vessel from 2.0 mm to 2.4 mm, corresponding to an increase from
      67% to 80% of the true vessel diameter. The line element beamforming approach is
      shown to be essential for achieving correct time-of-flight calculations, and
      hence avoid geometrical distortions. In Part II of this work, experimental
      results from a capacitive micromachined ultrasonic transducer with integrated
      roll-off apodization are given to validate the effect of integrating apodization
      into the line elements. 

PMID- 25974919
TI  - 3-D imaging using row-column-addressed arrays with integrated apodization- part
      ii: transducer fabrication and experimental results.
AB  - This paper demonstrates the fabrication, characterization, and experimental
      imaging results of a 62+62 element lambda/2-pitch row-column-addressed capacitive
      micromachined ultrasonic transducer (CMUT) array with integrated apodization. A
      new fabrication process was used to manufacture a 26.3 mm by 26.3 mm array using
      five lithography steps. The array includes an integrated apodization, presented
      in detail in Part I of this paper, which is designed to reduce the amplitude of
      the ghost echoes that are otherwise prominent for row-column-addressed arrays.
      Custom front-end electronics were produced with the capability of transmitting
      and receiving on all elements, and the option of disabling the integrated
      apodization. The center frequency and -6-dB fractional bandwidth of the array
      elements were 2.77 +/- 0.26 MHz and 102 +/- 10%, respectively. The surface
      transmit pressure at 2.5 MHz was 590 +/- 73 kPa, and the sensitivity was 0.299 +/
      0.090 V/Pa. The nearest neighbor crosstalk level was -23.9 +/- 3.7 dB, while the
      transmit-to-receive-elements crosstalk level was -40.2 +/- 3.5 dB. Imaging of a
      0.3-mm-diameter steel wire using synthetic transmit focusing with 62 single
      element emissions demonstrated axial and lateral FWHMs of 0.71 mm and 1.79 mm (f
      number: 1.4), respectively, compared with simulated axial and lateral FWHMs of
      0.69 mm and 1.76 mm. The dominant ghost echo was reduced by 15.8 dB in
      measurements using the integrated apodization compared with the disabled
      configuration. The effect was reproduced in simulations, showing a ghost echo
      reduction of 18.9 dB. 

PMID- 25974920
TI  - Spring is the Time for Renewal.

PMID- 25974921
TI  - "Evidence" and the treatment of alcohol use disorder.
AB  - Alcohol use disorder is an important public health problem for which evidence
      based treatments should be used. In the current article, two recent publications
      related to this topic (i.e., a featured article from The Atlantic and a brief
      guide from the Substance Abuse and Mental Health Services Administration
      [SAMHSA]) are critically evaluated. Both publications emphasize that evidence
      based medications are underused for the treatment of alcohol use disorder. The
      featured article was critical of faith-based Alcoholics Anonymous((r)) 12-step
      programs, but the critique was not based on a sound evaluation of research
      pertaining to their use. The brief guide prepared for SAMHSA was developed by a
      scientific consensus panel reviewing current evidence of the effectiveness of
      available medications, but focused only on those that have been approved by the
      U.S. Food and Drug Administration (FDA) for this indication, neglecting to
      describe potentially effective off-label use of other FDA-approved medications.

PMID- 25974922
TI  - Therapeutic doll play in the treatment of a severely impaired psychiatric
      inpatient: dramatic clinical improvements with a nontraditional nursing
      intervention.
AB  - Interest has grown in the use of doll therapy, particularly in geropsychiatric
      and dementia care settings. In a long-term state psychiatric hospital, a
      dollhouse-play activity was implemented in an effort to engage an acutely
      disturbed, middle-aged woman undergoing medication trials and whose symptoms had
      been refractory to conventional treatments. A schedule of nondirective dollhouse
      play activities was implemented over an 8-week period. Measures of behavioral
      change were tracked. Dramatic clinical improvements were seen, including
      significant reductions in verbal and physical aggression, use of as-needed
      medications, and need for close one-to-one monitoring. Improvements were seen
      prior to achievement of therapeutic drug levels. The patient was successfully
      discharged from the hospital. Doll play has recently been associated with
      clinical benefits in the care of patients with dementia and has long been
      deployed in childhood mental health treatment. The current findings suggest doll
      play may have applications as a time-limited intervention in the treatment of
      major psychiatric disorders in adults and warrants consideration when achieving
      therapeutic alliance has proven particularly challenging.

PMID- 25974923
TI  - Synthetic cannabinoids: the dangers of spicing it up.
AB  - Cannabinoids are the most commonly used illegal substances in the world. Spice
      and K2 are synthetic cannabinoid (SC) products that contain a mixture of herbs
      and plant matter combined with synthetic compounds similar to
      tetrahydrocannabinol, the psychoactive component of cannabis. Because the effects
      of Spice and K2 are similar to cannabis, many users are smoking these products as
      legal substitutes despite package labeling that they are not designed for human
      consumption. These SC products appeal to users because they are easily accessible
      and not readily detected in standard urine drug screens. The active components in
      SC products are highly potent and poorly characterized. Use of these agents has
      been associated with serious psychological and physiological side effects.
      Because abuse of SC products has become a national public health issue, nurses
      should be aware of the effects of SC compounds and must take a lead role in
      educating patients about the dangers of their use.

PMID- 25974925
TI  - An Active Learning Algorithm for Control of Epidural Electrostimulation.
AB  - Epidural electrostimulation has shown promise for spinal cord injury therapy.
      However, finding effective stimuli on the multi-electrode stimulating arrays
      employed requires a laborious manual search of a vast space for each patient.
      Widespread clinical application of these techniques would be greatly facilitated
      by an autonomous, algorithmic system which choses stimuli to simultaneously
      deliver effective therapy and explore this space. We propose a method based on GP
      BUCB, a Gaussian process bandit algorithm. In n = 4 spinally transected rats, we
      implant epidural electrode arrays and examine the algorithm's performance in
      selecting bipolar stimuli to elicit specified muscle responses. These responses
      are compared with temporally interleaved intra-animal stimulus selections by a
      human expert. GP-BUCB successfully controlled the spinal electrostimulation
      preparation in 37 testing sessions, selecting 670 stimuli. These sessions
      included sustained autonomous operations (ten-session duration). Delivered
      performance with respect to the specified metric was as good as or better than
      that of the human expert. Despite receiving no information as to anatomically
      likely locations of effective stimuli, GP-BUCB also consistently discovered such
      a pattern. Further, GP-BUCB was able to extrapolate from previous sessions'
      results to make predictions about performance in new testing sessions, while
      remaining sufficiently flexible to capture temporal variability. These results
      provide validation for applying automated stimulus selection methods to the
      problem of spinal cord injury therapy. 

PMID- 25974926
TI  - Characteristics of Dry Chin-Tuck Swallowing Vibrations and Sounds.
AB  - OBJECTIVE: The effects of the chin-tuck maneuver, a technique commonly employed
      to compensate for dysphagia, on cervical auscultation are not fully understood.
      Characterizing a technique that is known to affect swallowing function is an
      important step on the way to developing a new instrumentation-based swallowing
      screening tool. METHODS: In this study, we recorded data from 55 adult
      participants who each completed five saliva swallows in a chin-tuck position. The
      resulting data were processed using previously designed filtering and
      segmentation algorithms. We then calculated nine time-, frequency-, and time
      frequency-domain features for each independent signal. RESULTS: We found that
      multiple frequency- and time-domain features varied significantly between male
      and female subjects as well as between swallowing sounds and vibrations. However,
      our analysis showed that participant age did not play a significant role on the
      values of the extracted features. Finally, we found that various frequency
      features corresponding to swallowing vibrations did demonstrate statistically
      significant variation between the neutral and chin-tuck positions but sounds
      showed no changes between these two positions. CONCLUSION: The chin-tuck maneuver
      affects many facets of swallowing vibrations and sounds and its effects can be
      monitored via cervical auscultation. SIGNIFICANCE: These results suggest that a
      subject's swallowing technique does need to be accounted for when monitoring
      their performance with cervical auscultation-based instrumentation.

PMID- 25974927
TI  - Acoustic Features for the Identification of Coronary Artery Disease.
AB  - GOAL: Earlier studies have documented that coronary artery disease (CAD) produces
      weak murmurs, which might be detected through analysis of heart sounds. An
      electronic stethoscope with a digital signal processing unit could be a low cost
      and easily applied method for diagnosis of CAD. The current study is a search for
      heart sound features which might identify CAD. METHODS: Nine different types of
      features from five overlapping frequency bands were obtained and analyzed using
      435 recordings from 133 subjects. RESULTS: New features describing an increase in
      low-frequency power in CAD patients were identified. The features of the
      different types were relatively strongly correlated. Using a quadratic
      discriminant function, multiple features were combined into a CAD-score. The area
      under the receiving operating characteristic for the CAD score was 0.73 (95% CI:
      0.69-0.78). CONCLUSION: The result confirms that there is a potential in heart
      sounds for the diagnosis of CAD, but that further improvements are necessary to
      gain clinical relevance.

PMID- 25974928
TI  - Eye Tracking for Personal Visual Analytics.
AB  - In many research fields, eye tracking has become an established method to analyze
      the distribution of visual attention in various scenarios. With the trend toward
      increasingly affordable and easy-to-use consumer hardware, we expect mobile eye
      tracking to become ubiquitous, recording massive amounts of gaze data on a
      regular basis in everyday personal situations. To make use of this data, new
      approaches for personal visual analytics will be necessary to make the data
      accessible for non-expert users for self-reflection and re-experiencing
      interesting events. We discuss how eye tracking fits in the context of personal
      visual analytics, the challenges that arise with its application to everyday
      situations, and the research perspectives of personal eye tracking. Therefore,
      the extraction and representation of areas of interest (AOIs) in the recorded
      data is a crucial part of data processing. We present a new technique to
      represent these AOIs from multiple videos: the AOI cloud. In our example, we
      apply this technique to examine the personal encounters of a user with other
      persons. The technique provides an accessible user interface that is also
      applicable to touch devices and therefore suitable for an integration into the
      everyday life of a user.

PMID- 25974929
TI  - HaptiStylus: A Novel Stylus for Conveying Movement and Rotational Torque Effects.
AB  - With the emergence of pen-enabled tablets and mobile devices, stylus-based
      interaction has been receiving increasing attention. Unfortunately, styluses
      available on the market today are all passive instruments that are primarily used
      for writing and pointing. The article describes a novel stylus, HaptiStylus,
      which is capable of conveying certain vibrotactile and inertial haptic effects to
      the user. The stylus is equipped with two vibration actuators at each end that
      are used to create a tactile sensation of up and down movement along the stylus.
      The stylus is also embedded with a DC motor, which helps create a sense of
      bidirectional rotational torque along the pen. Psychophysical experimental
      results and practical application use-case studies show that the proposed device
      can effectively convey movement and rotational torque information to the user. 

PMID- 25974930
TI  - Revealing Visualization Insights from Quantified-Selfers' Personal Data
      Presentations.
AB  - Data visualization and analytics research has great potential to empower people
      to improve their lives by leveraging their own personal data. However, most
      Quantified-Selfers are neither visualization experts nor data scientists.
      Consequently, their visualizations of their data are often not ideal for
      conveying their insights. Aiming to design a visualization system to help non
      experts explore and present their personal data, we conducted a pre-design
      empirical study. Through the lens of Quantified-Selfers, we examined what
      insights people gain specifically from their personal data and how they use
      visualizations to communicate their insights. Based on our analysis of 30
      Quantified Self presentations, we characterized eight insight types (detail, self
      reflection, trend, comparison, correlation, data summary, distribution, outlier)
      and mapped the visual annotations used to communicate them. We further discussed
      four areas for the design of personal visualization systems, including support
      for encouraging self-reflection, gaining valid insight, communicating insight,
      and using visual annotations.

PMID- 25974931
TI  - Understanding Digital Note-Taking Practice for Visualization.
AB  - We present results and design implications from a study of digital note-taking
      practice to examine how visualization can support revisitation, reflection, and
      collaboration around notes. As digital notebooks become common forms of external
      memory, keeping track of volumes of content is increasingly difficult.
      Information visualization tools can help give note-takers an overview of their
      content and allow them to explore diverse sets of notes, find and organize
      related content, and compare their notes with their collaborators. To ground the
      design of such tools, we conducted a detailed mixed-methods study of digital note
      taking practice. We identify a variety of different editing, organization, and
      sharing methods used by digital note-takers, many of which result in notes
      becoming "lost in the pile''. These findings form the basis for our design
      considerations that examine how visualization can support the revisitation,
      organization, and sharing of digital notes.

PMID- 25974932
TI  - Variance Estimation for Myocardial Blood Flow by Dynamic PET.
AB  - The estimation of myocardial blood flow (MBF) by (13)N-ammonia or (82)Rb dynamic
      PET typically relies on an empirically determined generalized Renkin-Crone
      equation to relate the kinetic parameter K1 to MBF. Because the Renkin-Crone
      equation defines MBF as an implicit function of K1, the MBF variance cannot be
      determined using standard error propagation techniques. To overcome this
      limitation, we derived novel analytical approximations that provide first- and
      second-order estimates of MBF variance in terms of the mean and variance of K1
      and the Renkin-Crone parameters. The accuracy of the analytical expressions was
      validated by comparison with Monte Carlo simulations, and MBF variance was
      evaluated in clinical (82)Rb dynamic PET scans. For both (82)Rb and (13)N
      ammonia, good agreement was observed between both (first- and second-order)
      analytical variance expressions and Monte Carlo simulations, with moderately
      better agreement for second-order estimates. The contribution of the Renkin-Crone
      relation to overall MBF uncertainty was found to be as high as 68% for (82)Rb and
      35% for (13)N-ammonia. For clinical (82)Rb PET data, the conventional practice of
      neglecting the statistical uncertainty in the Renkin-Crone parameters resulted in
      underestimation of the coefficient of variation of global MBF and coronary flow
      reserve by 14-49%. Knowledge of MBF variance is essential for assessing the
      precision and reliability of MBF estimates. The form and statistical uncertainty
      in the empirical Renkin-Crone relation can make substantial contributions to the
      variance of MBF. The novel analytical variance expressions derived in this work
      enable direct estimation of MBF variance which includes this previously neglected
      contribution.

PMID- 25974934
TI  - Heterogeneous Graph Propagation for Large-Scale Web Image Search.
AB  - State-of-the-art web image search frameworks are often based on the bag-of-visual
      words (BoVWs) model and the inverted index structure. Despite the simplicity,
      efficiency, and scalability, they often suffer from low precision and/or recall,
      due to the limited stability of local features and the considerable information
      loss on the quantization stage. To refine the quality of retrieved images,
      various postprocessing methods have been adopted after the initial search
      process. In this paper, we investigate the online querying process from a graph
      based perspective. We introduce a heterogeneous graph model containing both image
      and feature nodes explicitly, and propose an efficient reranking approach
      consisting of two successive modules, i.e., incremental query expansion and image
      feature voting, to improve the recall and precision, respectively. Compared with
      the conventional reranking algorithms, our method does not require using
      geometric information of visual words, therefore enjoys low consumptions of both
      time and memory. Moreover, our method is independent of the initial search
      process, and could cooperate with many BoVW-based image search pipelines, or
      adopted after other postprocessing algorithms. We evaluate our approach on large
      scale image search tasks and verify its competitive search performance. 

PMID- 25974933
TI  - Comparison of Acoustic Radiation Force Impulse Imaging Derived Carotid Plaque
      Stiffness With Spatially Registered MRI Determined Composition.
AB  - Measurements of plaque stiffness may provide important prognostic and diagnostic
      information to help clinicians distinguish vulnerable plaques containing soft
      lipid pools from more stable, stiffer plaques. In this preliminary study, we
      compare in vivo ultrasonic Acoustic Radiation Force Impulse (ARFI) imaging
      derived measures of carotid plaque stiffness with composition determined by
      spatially registered Magnetic Resonance Imaging (MRI) in five human subjects with
      stenosis > 50%. Ultrasound imaging was implemented on a commercial diagnostic
      scanner with custom pulse sequences to collect spatially registered 2D
      longitudinal B-mode and ARFI images. A standardized, multi-contrast weighted MRI
      sequence was used to obtain 3D Time of Flight (TOF), T1 weighted (T1W), T2
      weighted (T2W), and Proton Density Weighted (PDW) transverse image stacks of
      volumetric data. The MRI data was segmented to identify lipid, calcium, and
      normal loose matrix components using commercially available software. 3D MRI
      segmented plaque models were rendered and spatially registered with 2D B-mode
      images to create fused ultrasound and MRI volumetric images for each subject.
      ARFI imaging displacements in regions of interest (ROIs) derived from MRI
      segmented contours of varying composition were compared. Regions of calcium and
      normal loose matrix components identified by MRI presented as homogeneously stiff
      regions of similarly low (typically ~ 1 MUm) displacement in ARFI imaging. MRI
      identified lipid pools > 2 mm(2), found in three out of five subjects, presented
      as softer regions of increased displacement that were on average 1.8 times
      greater than the displacements in adjacent regions of loose matrix components in
      spatially registered ARFI images. This work provides early evidence supporting
      the use of ARFI imaging to noninvasively identify lipid regions in carotid artery
      plaques in vivo that are believed to increase the propensity of a plaque to
      rupture. Additionally, the results provide early training data for future studies
      and aid in the interpretation and possible clinical utility of ARFI imaging for
      identifying the elusive vulnerable plaque. 

PMID- 25974935
TI  - A Regularization Approach to Blind Deblurring  and Denoising of QR Barcodes.
AB  - QR bar codes are prototypical images for which part of the image is a priori
      known (required patterns). Open source bar code readers, such as ZBar, are
      readily available. We exploit both these facts to provide and assess purely
      regularization-based methods for blind deblurring of QR bar codes in the presence
      of noise.

PMID- 25974936
TI  - Model-based adaptive 3D sonar reconstruction in reverberating environments.
AB  - In this paper, we propose a novel model-based approach for 3D underwater scene
      reconstruction, i.e., bathymetry, for side scan sonar arrays in complex and
      highly reverberating environments like shallow water areas. The presence of
      multipath echoes and volume reverberation generates false depth estimates. To
      improve the resulting bathymetry, this paper proposes and develops an adaptive
      filter, based on several original geometrical models. This multimodel approach
      makes it possible to track and separate the direction of arrival trajectories of
      multiple echoes impinging the array. Echo tracking is perceived as a model-based
      processing stage, incorporating prior information on the temporal evolution of
      echoes in order to reject cluttered observations generated by interfering echoes.
      The results of the proposed filter on simulated and real sonar data showcase the
      clutter-free and regularized bathymetric reconstruction. Model validation is
      carried out with goodness of fit tests, and demonstrates the importance of model
      based processing for bathymetry reconstruction. 

PMID- 25974937
TI  - Random geometric prior forest for multiclass object segmentation.
AB  - Recent advances in object detection have led to the development of segmentation
      by detection approaches that integrate top-down geometric priors for multiclass
      object segmentation. A key yet under-addressed issue in utilizing top-down cues
      for the problem of multiclass object segmentation by detection is efficiently
      generating robust and accurate geometric priors. In this paper, we propose a
      random geometric prior forest scheme to obtain object-adaptive geometric priors
      efficiently and robustly. In the scheme, a testing object first searches for
      training neighbors with similar geometries using the random geometric prior
      forest, and then the geometry of the testing object is reconstructed by linearly
      combining the geometries of its neighbors. Our scheme enjoys several favorable
      properties when compared with conventional methods. First, it is robust and very
      fast because its inference does not suffer from bad initializations, poor local
      minimums or complex optimization. Second, the figure/ground geometries of
      training samples are utilized in a multitask manner. Third, our scheme is object
      adaptive but does not require the labeling of parts or poselets, and thus, it is
      quite easy to implement. To demonstrate the effectiveness of the proposed scheme,
      we integrate the obtained top-down geometric priors with conventional bottom-up
      color cues in the frame of graph cut. The proposed random geometric prior forest
      achieves the best segmentation results of all of the methods tested on
      VOC2010/2012 and is 90 times faster than the current state-of-the-art method. 

PMID- 25974938
TI  - PISA: pixelwise image saliency by aggregating complementary appearance contrast
      measures with edge-preserving coherence.
AB  - Driven by recent vision and graphics applications such as image segmentation and
      object recognition, computing pixel-accurate saliency values to uniformly
      highlight foreground objects becomes increasingly important. In this paper, we
      propose a unified framework called pixelwise image saliency aggregating (PISA)
      various bottom-up cues and priors. It generates spatially coherent yet detail
      preserving, pixel-accurate, and fine-grained saliency, and overcomes the
      limitations of previous methods, which use homogeneous superpixel based and color
      only treatment. PISA aggregates multiple saliency cues in a global context, such
      as complementary color and structure contrast measures, with their spatial priors
      in the image domain. The saliency confidence is further jointly modeled with a
      neighborhood consistence constraint into an energy minimization formulation, in
      which each pixel will be evaluated with multiple hypothetical saliency levels.
      Instead of using global discrete optimization methods, we employ the cost-volume
      filtering technique to solve our formulation, assigning the saliency levels
      smoothly while preserving the edge-aware structure details. In addition, a faster
      version of PISA is developed using a gradient-driven image subsampling strategy
      to greatly improve the runtime efficiency while keeping comparable detection
      accuracy. Extensive experiments on a number of public data sets suggest that PISA
      convincingly outperforms other state-of-the-art approaches. In addition, with
      this work, we also create a new data set containing 800 commodity images for
      evaluating saliency detection. 

PMID- 25974939
TI  - Single Image Superresolution via Directional  Group Sparsity and Directional
      Features.
AB  - Single image superresolution (SR) aims to construct a high-resolution version
      from a single low-resolution (LR) image. The SR reconstruction is challenging
      because of the missing details in the given LR image. Thus, it is critical to
      explore and exploit effective prior knowledge for boosting the reconstruction
      performance. In this paper, we propose a novel SR method by exploiting both the
      directional group sparsity of the image gradients and the directional features in
      similarity weight estimation. The proposed SR approach is based on two
      observations: 1) most of the sharp edges are oriented in a limited number of
      directions and 2) an image pixel can be estimated by the weighted averaging of
      its neighbors. In consideration of these observations, we apply the curvelet
      transform to extract directional features which are then used for region
      selection and weight estimation. A combined total variation regularizer is
      presented which assumes that the gradients in natural images have a
      straightforward group sparsity structure. In addition, a directional nonlocal
      means regularization term takes pixel values and directional information into
      account to suppress unwanted artifacts. By assembling the designed regularization
      terms, we solve the SR problem of an energy function with minimal reconstruction
      error by applying a framework of templates for first-order conic solvers. The
      thorough quantitative and qualitative results in terms of peak signal-to-noise
      ratio, structural similarity, information fidelity criterion, and preference
      matrix demonstrate that the proposed approach achieves higher quality SR
      reconstruction than the state-of-the-art algorithms.

PMID- 25974940
TI  - Disparity Estimation on Stereo Mammograms.
AB  - We consider the problem of depth estimation on digital stereo mammograms. Being
      able to elucidate 3D information from stereo mammograms is an important precursor
      to conducting 3D digital analysis of data from this promising new modality. The
      problem is generally much harder than the classic stereo matching problem on
      visible light images of the natural world, since nearly all of the 3D structural
      information of interest exists as complex network of multilayered, heavily
      occluded curvilinear structures. Toward addressing this difficult problem, we
      formulate a new stereo model that minimizes a global energy functional to densely
      estimate disparity on stereo mammogram images, by introducing a new singularity
      index as a constraint to obtain better estimates of disparity along critical
      curvilinear structures. Curvilinear structures, such as vasculature and spicules,
      are particularly salient structures in the breast, and being able to accurately
      position them in 3D is a valuable goal. Experiments on synthetic images with
      known ground truth and on real stereo mammograms highlight the advantages of the
      proposed stereo model over the canonical stereo model.

PMID- 25974941
TI  - Stochastic blind motion deblurring.
AB  - Blind motion deblurring from a single image is a highly under-constrained problem
      with many degenerate solutions. A good approximation of the intrinsic image can,
      therefore, only be obtained with the help of prior information in the form of
      (often nonconvex) regularization terms for both the intrinsic image and the
      kernel. While the best choice of image priors is still a topic of ongoing
      investigation, this research is made more complicated by the fact that
      historically each new prior requires the development of a custom optimization
      method. In this paper, we develop a stochastic optimization method for blind
      deconvolution. Since this stochastic solver does not require the explicit
      computation of the gradient of the objective function and uses only efficient
      local evaluation of the objective, new priors can be implemented and tested very
      quickly. We demonstrate that this framework, in combination with different image
      priors produces results with Peak Signal-to-Noise Ratio (PSNR) values that match
      or exceed the results obtained by much more complex state-of-the-art blind motion
      deblurring algorithms. 

PMID- 25974942
TI  - Assessments of Muscle Oxygenation and Cortical Activity Using Functional Near
      infrared Spectroscopy in Healthy Adults During Hybrid Activation.
AB  - Hybrid activation (HA), patterned electrical stimulation (ES) superimposed on
      attempted voluntary movement in close synchrony, can augment muscle force output.
      It has been proposed for limb function restoration and neuromodulation. Limited
      studies have been performed to investigate the influences of HA on muscle
      oxygenation and brain cortical activity. The present study investigates muscle
      oxygenation and cortical activity during isometric knee extension tasks with
      voluntary contraction (VOL) only, ES only, and with HA at three stimulation
      intensities, namely 10 mA (HA-I), 30 mA (HA-II), and 50 mA (HA-III). A frequency
      domain near-infrared spectroscopy system was employed to assess the muscle
      oxygenation in the vastus lateralis as well as the cortical activity from the
      bilateral sensorimotor cortices (SMCs), premotor cortices (PMCs), and
      supplementary motor areas (SMAs). Our results show that the increased ES
      contribution during HA significantly increased O2 demand in working muscle,
      implying that the intervention of ES accelerates the muscle metabolism during
      muscle contraction. For cortical activation, ES only had a similar cortical
      activation pattern to that during VOL but with lower activation in SMCs, PMCs,
      and SMAs. Augmented sensorimotor activation was observed during the HA-II
      condition. The enhanced level of cortical activation during HA was not only
      affected by the ES contribution within HA but also related to the functional
      specificity of cortical areas. Our results suggest that HA can effectively
      enhance the muscle oxygen demand as well as the activation of cortical regions,
      and that the ES contribution within HA is a key factor. 

PMID- 25974944
TI  - Transceiver Design for CMUT-Based Super-Resolution Ultrasound Imaging.
AB  - A recently introduced structure for the capacitive micromachined ultrasonic
      transducers (CMUTs) has focused on the applications of the asymmetric mode of
      vibration and has shown promising results in construction of super-resolution
      ultrasound images. This paper presents the first implementation and experimental
      results of a transceiver circuit to interface such CMUT structures. The multiple
      input/multiple output receiver in this work supports both fundamental and
      asymmetric modes of operation and includes transimpedance amplifiers and low
      power variable-gain stages. These circuit blocks are designed considering the
      trade-offs between gain, input impedance, noise, linearity and power consumption.
      The high-voltage transmitter can generate pulse voltages up to 60 V while
      occupying a considerably small area. The overall circuit is designed and laid out
      in a 0.35 MUm CMOS process and a four-channel transceiver occupies 0.86 * 0.38
      mm(2). The prototype chip is characterized in both electrical and mechanical
      domains. Measurement results show that each receiver channel has a nominal gain
      of 110 dBOmega with a 3 dB bandwidth of 9 MHz while consuming 1.02 mW from a 3.3
      V supply. The receiver is also highly linear, with 1 dB compression point of
      minimum 1.05 V which is considerably higher than the previously reported designs.
      The transmitter consumes 98.1 mW from a 30 V supply while generating 1.38 MHz, 30
      V pulses. The CMOS-CMUT system is tested in the transmit mode and shows full
      functionality in air medium.

PMID- 25974943
TI  - A Wearable Patch to Enable Long-Term Monitoring of Environmental, Activity and
      Hemodynamics Variables.
AB  - We present a low power multi-modal patch designed for measuring activity,
      altitude (based on high-resolution barometric pressure), a single-lead
      electrocardiogram, and a tri-axial seismocardiogram (SCG). Enabled by a novel
      embedded systems design methodology, this patch offers a powerful means of
      monitoring the physiology for both patients with chronic cardiovascular diseases,
      and the general population interested in personal health and fitness measures.
      Specifically, to the best of our knowledge, this patch represents the first
      demonstration of combined activity, environmental context, and hemodynamics
      monitoring, all on the same hardware, capable of operating for longer than 48
      hours at a time with continuous recording. The three-channels of SCG and one-lead
      ECG are all sampled at 500 Hz with high signal-to-noise ratio, the pressure
      sensor is sampled at 10 Hz, and all signals are stored to a microSD card with an
      average current consumption of less than 2 mA from a 3.7 V coin cell (LIR2450)
      battery. In addition to electronic characterization, proof-of-concept exercise
      recovery studies were performed with this patch, suggesting the ability to
      discriminate between hemodynamic and electrophysiology response to light,
      moderate, and heavy exercise. 

PMID- 25974946
TI  - Multi-Path Model and Sensitivity Analysis for Galvanic Coupled Intra-Body
      Communication Through Layered Tissue.
AB  - New medical procedures promise continuous patient monitoring and drug delivery
      through implanted sensors and actuators. When over the air wireless radio
      frequency (OTA-RF) links are used for intra-body implant communication, the
      network incurs heavy energy costs owing to absorption within the human tissue.
      With this motivation, we explore an alternate form of intra-body communication
      that relies on weak electrical signals, instead of OTA-RF. To demonstrate the
      feasibility of this new paradigm for enabling communication between sensors and
      actuators embedded within the tissue, or placed on the surface of the skin, we
      develop a rigorous analytical model based on galvanic coupling of low energy
      signals. The main contributions in this paper are: (i) developing a suite of
      analytical expressions for modeling the resulting communication channel for weak
      electrical signals in a three dimensional multi-layered tissue structure, (ii)
      validating and verifying the model through extensive finite element simulations,
      published measurements in existing literature, and experiments conducted with
      porcine tissue, (iii) designing the communication framework with safety
      considerations, and analyzing the influence of different network and hardware
      parameters such as transmission frequency and electrode placements. Our results
      reveal a close agreement between theory, simulation, literature and experimental
      findings, pointing to the suitability of the model for quick and accurate channel
      characterization and parameter estimation for networked and implanted sensors. 

PMID- 25974945
TI  - A CMOS Neural Interface for a Multichannel Vestibular Prosthesis.
AB  - We present a high-voltage CMOS neural-interface chip for a multichannel
      vestibular prosthesis (MVP) that measures head motion and modulates vestibular
      nerve activity to restore vision- and posture-stabilizing reflexes. This
      application specific integrated circuit neural interface (ASIC-NI) chip was
      designed to work with a commercially available microcontroller, which controls
      the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses
      with 9-bit programmable current amplitude via 16 stimulation channels. The chip
      was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can
      accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches
      using biphasic current pulses up to 1.45+/-0.06 mA with durations as short as 10
      MUs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each
      channel, enabling it to perform complex multipolar stimulation. The ASIC-NI
      replaces discrete components that cover nearly half of the 2nd generation MVP
      (MVP2) printed circuit board, reducing the MVP system size by 48% and power
      consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a
      rhesus monkey produced reflexive eye movement responses to prosthetic stimulation
      similar to those observed when using the MVP2. Sinusoidal modulation of stimulus
      pulse rate from 68-130 pulses per second at frequencies from 0.1 to 5 Hz elicited
      appropriately-directed slow phase eye velocities ranging in amplitude from 1.9
      16.7  degrees /s for the MVP2 and 2.0-14.2  degrees /s for the MVP2A. The eye
      velocities evoked by MVP2 and MVP2A showed no significant difference ( t-test,
      p=0.34), suggesting that the MVP2A achieves performance at least as good as the
      larger MVP2.

PMID- 25974947
TI  - A 16 * 16 CMOS Capacitive Biosensor Array Towards Detection of Single Bacterial
      Cell.
AB  - We present a 16 * 16 CMOS biosensor array aiming at impedance detection of whole
      cell bacteria. Each 14 MUm * 16 MUm pixel comprises high-sensitive passivated
      microelectrodes connected to an innovative readout interface based on charge
      sharing principle for capacitance-to-voltage conversion and subthreshold gain
      stage to boost the sensitivity. Fabricated in a 0.25 MUm CMOS process, the
      capacitive array was experimentally shown to perform accurate dielectric
      measurements of the electrolyte up to electrical conductivities of 0.05 S/m, with
      maximal sensitivity of 55 mV/fF and signal-to-noise ratio (SNR) of 37 dB. As
      biosensing proof of concept, real-time detection of Staphylococcus epidermidis
      binding events was experimentally demonstrated and provides detection limit of
      ca. 7 bacteria per pixel and sensitivity of 2.18 mV per bacterial cell. Models
      and simulations show good matching with experimental results and provide a
      comprehensive analysis of the sensor and circuit system. Advantages, challenges
      and limits of the proposed capacitive biosensor array are finally described with
      regards to literature. With its small area and low power consumption, the present
      capacitive array is particularly suitable for portable point-of-care (PoC)
      diagnosis tools and lab-on-chip (LoC) systems.

PMID- 25974950
TI  - Robust Gradient Learning With Applications.
AB  - This paper addresses the robust gradient learning (RGL) problem. Gradient
      learning models aim at learning the gradient vector of some target functions in
      supervised learning problems, which can be further used to applications, such as
      variable selection, coordinate covariance estimation, and supervised dimension
      reduction. However, existing GL models are not robust to outliers or heavy-tailed
      noise. This paper provides an RGL framework to address this problem in both
      regression and classification. This is achieved by introducing a robust
      regression loss function and proposing a robust classification loss. Moreover,
      our RGL algorithm works in an instance-based kernelized dictionary instead of
      some fixed reproducing kernel Hilbert space, which may provide more flexibility.
      To solve the proposed nonconvex model, a simple computational algorithm based on
      gradient descent is provided and the convergence of the proposed method is also
      analyzed. We then apply the proposed RGL model to applications, such as nonlinear
      variable selection and coordinate covariance estimation. The efficiency of our
      proposed model is verified on both synthetic and real data sets. 

PMID- 25974949
TI  - Learning of Temporal and Spatial Movement Aspects: A Comparison of Four Types of
      Haptic Control and Concurrent Visual Feedback.
AB  - In literature, the effectiveness of haptics for motor learning is controversially
      discussed. Haptics is believed to be effective for motor learning in general;
      however, different types of haptic control enhance different movement aspects.
      Thus, in dependence on the movement aspects of interest, one type of haptic
      control may be effective whereas another one is not. Therefore, in the current
      work, it was investigated if and how different types of haptic controllers affect
      learning of spatial and temporal movement aspects. In particular, haptic
      controllers that enforce active participation of the participants were expected
      to improve spatial aspects. Only haptic controllers that provide feedback about
      the task's velocity profile were expected to improve temporal aspects. In a study
      on learning a complex trunk-arm rowing task, the effect of training with four
      different types of haptic control was investigated: position control, path
      control, adaptive path control, and reactive path control. A fifth group
      (control) trained with visual concurrent augmented feedback. As hypothesized, the
      position controller was most effective for learning of temporal movement aspects,
      while the path controller was most effective in teaching spatial movement aspects
      of the rowing task. Visual feedback was also effective for learning temporal and
      spatial movement aspects.

PMID- 25974951
TI  - An Asynchronous Recurrent Network of Cellular Automaton-Based Neurons and Its
      Reproduction of Spiking Neural Network Activities.
AB  - Modeling and implementation approaches for the reproduction of input-output
      relationships in biological nervous tissues contribute to the development of
      engineering and clinical applications. However, because of high nonlinearity, the
      traditional modeling and implementation approaches encounter difficulties in
      terms of generalization ability (i.e., performance when reproducing an unknown
      data set) and computational resources (i.e., computation time and circuit
      elements). To overcome these difficulties, asynchronous cellular automaton-based
      neuron (ACAN) models, which are described as special kinds of cellular automata
      that can be implemented as small asynchronous sequential logic circuits have been
      proposed. This paper presents a novel type of such ACAN and a theoretical
      analysis of its excitability. This paper also presents a novel network of such
      neurons, which can mimic input-output relationships of biological and nonlinear
      ordinary differential equation model neural networks. Numerical analyses confirm
      that the presented network has a higher generalization ability than other major
      modeling and implementation approaches. In addition, Field-Programmable Gate
      Array-implementations confirm that the presented network requires lower
      computational resources. 

PMID- 25974948
TI  - Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration.
AB  - Inadequate replacement of lost ventricular myocardium from myocardial infarction
      leads to heart failure. Investigating the regenerative capacity of mammalian
      hearts represents an emerging direction for tissue engineering and cell-based
      therapy. Recent advances in stem cells hold promise to restore cardiac functions.
      However, embryonic or induced pluripotent stem cell-derived cardiomyocytes lack
      functional phenotypes of the native myocardium, and transplanted tissues are not
      fully integrated for synchronized electrical and mechanical coupling with the
      host. In this context, this review highlights the mechanical and electrical
      strategies to promote cardiomyocyte maturation and integration, and to assess the
      functional phenotypes of regenerating myocardium. Simultaneous
      microelectrocardiogram and high-frequency ultrasound techniques will also be
      introduced to assess electrical and mechanical coupling for small animal models
      of heart regeneration. 

PMID- 25974952
TI  - Finite-Time Consensus of Multiagent Systems With a Switching Protocol.
AB  - In this paper, we study the problem of finite-time consensus of multiagent
      systems on a fixed directed interaction graph with a new protocol. Existing
      finite-time consensus protocols can be divided into two types: 1) continuous and
      2) discontinuous, which were studied separately in the past. In this paper, we
      deal with both continuous and discontinuous protocols simultaneously, and design
      a centralized switching consensus protocol such that the finite-time consensus
      can be realized in a fast speed. The switching protocol depends on the range of
      the initial disagreement of the agents, for which we derive an exact bound to
      indicate at what time a continuous or a discontinuous protocol should be selected
      to use. Finally, we provide two numerical examples to illustrate the superiority
      of the proposed protocol and design method. 

PMID- 25974953
TI  - Mixed H-Infinity and Passive Filtering for Discrete Fuzzy Neural Networks With
      Stochastic Jumps and Time Delays.
AB  - In this brief, the problems of the mixed H-infinity and passivity performance
      analysis and design are investigated for discrete time-delay neural networks with
      Markovian jump parameters represented by Takagi-Sugeno fuzzy model. The main
      purpose of this brief is to design a filter to guarantee that the augmented
      Markovian jump fuzzy neural networks are stable in mean-square sense and satisfy
      a prescribed passivity performance index by employing the Lyapunov method and the
      stochastic analysis technique. Applying the matrix decomposition techniques,
      sufficient conditions are provided for the solvability of the problems, which can
      be formulated in terms of linear matrix inequalities. A numerical example is also
      presented to illustrate the effectiveness of the proposed techniques. 

PMID- 25974954
TI  - Global nonlinear kernel prediction for large data set with a particle swarm
      optimized interval support vector regression.
AB  - A new global nonlinear predictor with a particle swarm-optimized interval support
      vector regression (PSO-ISVR) is proposed to address three issues (viz., kernel
      selection, model optimization, kernel method speed) encountered when applying SVR
      in the presence of large data sets. The novel prediction model can reduce the SVR
      computing overhead by dividing input space and adaptively selecting the optimized
      kernel functions to obtain optimal SVR parameter by PSO. To quantify the quality
      of the predictor, its generalization performance and execution speed are
      investigated based on statistical learning theory. In addition, experiments using
      synthetic data as well as the stock volume weighted average price are reported to
      demonstrate the effectiveness of the developed models. The experimental results
      show that the proposed PSO-ISVR predictor can improve the computational
      efficiency and the overall prediction accuracy compared with the results produced
      by the SVR and other regression methods. The proposed PSO-ISVR provides an
      important tool for nonlinear regression analysis of big data. 

PMID- 25974955
TI  - Regulatory elements in low-methylated regions predict directional change of gene
      expression.
AB  - Recent studies on methylomes obtained from the whole genome bisulfite sequencing
      (WGBS) indicate that low-methylated regions (LMRs) are related to potential
      active distal regulatory regions such as enhancers in mammalian genomes. To
      investigate the potential effect of regulatory elements in LMRs on gene
      expression, we proposed penalized logistic regression models to predict the
      directional change of differentially expressed genes using predicted
      transcription factor binding sites (TFBSs) in LMRs that are distinctive between
      two cell types. We evaluated our models on four cell types where the WGBS and RNA
      seq data were available. The average area under the ROC curve (AUC) from the
      tenfold cross validation was computed over the six pairs of cell types in each
      model. The models using TFBSs in LMRs in intergenic or genebody region are more
      predictive (AUC 0.71 and 0.66, respectively) compared with the one using TFBSs
      from promoter regions alone (AUC 0.62). When using a model that combines TFBSs in
      LMRs from both intergenic and genebody regions, the best prediction was obtained
      (AUC 0.78). Our models are capable of identifying subsets of LMRs that are
      significantly enriched for the ChIP-seq binding sites of the insulator protein
      CTCF and p300 co-activator and other transcription factors. Our framework
      provides further evidence of putative distal regulatory elements from LMRs
      located in intergenic and genebody regions. 

PMID- 25974956
TI  - Admission Control Over Internet of Vehicles Attached With Medical Sensors for
      Ubiquitous Healthcare Applications.
AB  - Wireless technologies and vehicle-mounted or wearable medical sensors are
      pervasive to support ubiquitous healthcare applications. However, a critical
      issue of using wireless communications under a healthcare scenario rests at the
      electromagnetic interference (EMI) caused by radio frequency transmission. A high
      level of EMI may lead to a critical malfunction of medical sensors, and in such a
      scenario, a few users who are not transmitting emergency data could be required
      to reduce their transmit power or even temporarily disconnect from the network in
      order to guarantee the normal operation of medical sensors as well as the
      transmission of emergency data. In this paper, we propose a joint power and
      admission control algorithm to schedule the users' transmission of medical data.
      The objective of this algorithm is to minimize the number of users who are forced
      to disconnect from the network while keeping the EMI on medical sensors at an
      acceptable level. We show that a fixed point of proposed algorithm always exists,
      and at the fixed point, our proposed algorithm can minimize the number of low
      priority users who are required to disconnect from the network. Numerical results
      illustrate that the proposed algorithm can achieve robust performance against the
      variations of mobile hospital environments.

PMID- 25974957
TI  - Identifying Physical Activity Profiles in COPD Patients Using Topic Models.
AB  - With the growing amount of physical activity (PA) measures, the need for methods
      and algorithms that automatically analyze and interpret unannotated data
      increases. In this paper, PA is seen as a combination of multimodal constructs
      that can cooccur in different ways and proportions during the day. The design of
      a methodology able to integrate and analyze them is discussed, and its operation
      is illustrated by applying it to a dataset comprising data from COPD patients and
      healthy subjects acquired in daily life. The method encompasses different stages.
      The first stage is a completely automated method of labeling low-level multimodal
      PA measures. The information contained in the PA labels are further structured
      using topic modeling techniques, a machine learning method from the text
      processing community. The topic modeling discovers the main themes that pervade a
      large set of data. In our case, topic models discover PA routines that are active
      in the assessed days of the subjects under study. Applying the designed algorithm
      to our data provides new learnings and insights. As expected, the algorithm
      discovers that PA routines for COPD patients and healthy subjects are
      substantially different regarding their composition and moments in time in which
      transitions occur. Furthermore, it shows consistent trends relating to disease
      severity as measured by standard clinical practice. 

PMID- 25974958
TI  - Feature Selection Based on the SVM Weight Vector for Classification of Dementia.
AB  - Computer-aided diagnosis of dementia using a support vector machine (SVM) can be
      improved with feature selection. The relevance of individual features can be
      quantified from the SVM weights as a significance map (p-map). Although these p
      maps previously showed clusters of relevant voxels in dementia-related brain
      regions, they have not yet been used for feature selection. Therefore, we
      introduce two novel feature selection methods based on p-maps using a direct
      approach (filter) and an iterative approach (wrapper). To evaluate these p-map
      feature selection methods, we compared them with methods based on the SVM weight
      vector directly, t-statistics, and expert knowledge. We used MRI data from the
      Alzheimer's disease neuroimaging initiative classifying Alzheimer's disease (AD)
      patients, mild cognitive impairment (MCI) patients who converted to AD (MCIc),
      MCI patients who did not convert to AD (MCInc), and cognitively normal controls
      (CN). Features for each voxel were derived from gray matter morphometry. Feature
      selection based on the SVM weights gave better results than t-statistics and
      expert knowledge. The p-map methods performed slightly better than those using
      the weight vector. The wrapper method scored better than the filter method.
      Recursive feature elimination based on the p-map improved most for AD-CN: the
      area under the receiver-operating-characteristic curve (AUC) significantly
      increased from 90.3% without feature selection to 92.0% when selecting 1.5%-3% of
      the features. This feature selection method also improved the other
      classifications: AD-MCI 0.1% improvement in AUC (not significant), MCI-CN 0.7%,
      and MCIc-MCInc 0.1% (not significant). Although the performance improvement due
      to feature selection was limited, the methods based on the p-map generally had
      the best performance, and were therefore better in estimating the relevance of
      individual features. 

PMID- 25974959
TI  - Estimating Energy Expenditure With Multiple Models Using Different Wearable
      Sensors.
AB  - This paper presents an approach to designing a method for the estimation of human
      energy expenditure (EE). The approach first evaluates different sensors and their
      combinations. After that, multiple regression models are trained utilizing data
      from different sensors. The EE estimation method designed in this way was
      evaluated on a dataset containing a wide range of activities. It was compared
      against three competing state-of-the-art approaches, including the BodyMedia Fit
      armband, the leading consumer EE estimation device. The results show that the
      proposed method outperforms the competition by up to 10.2 percentage points.

PMID- 25974960
TI  - Solving Potential Games With Dynamical Constraint.
AB  - We solve N -player potential games with dynamical constraint in this paper.
      Potential games with stable dynamics are first considered followed by one type of
      potential games without inherently stable dynamics. Different from most of the
      existing Nash seeking methods, we provide an extremum seeking-based method that
      does not require explicit information on the game dynamics or the payoff
      functions. Only measurements of the payoff functions are needed in the game
      strategy synthesis. Lie bracket approximation is used for the analysis of the
      proposed Nash seeking scheme. A singularly semi-globally practically uniformly
      asymptotically stable result is presented for potential games with stable
      dynamics and an ultimately bounded result is provided for potential games without
      inherently stable dynamics. For first-order perturbed integrator-type dynamics,
      we employ an extended-state observer to deal with the disturbance such that
      better convergence is achievable. Stability of the closed-loop system is proven
      and the ultimate bound is quantified. Numerical examples are presented to verify
      the effectiveness of the proposed methods. 

PMID- 25974961
TI  - Sexually selected sex differences in competitiveness explain sex differences in
      changes in drinking game participation.
AB  - Drinking games are a risk factor for behavioral and health problems among
      university students. Previous cross-sectional research by Hone, Carter, and
      McCullough (2013) replicated well-established sex differences in drinking game
      behaviors (i.e., that men are more active drinking game participants than are
      women) and university drinking problems more generally. Hone et al. (2013) also
      found that these male-specific behavioral patterns are attributable in part to
      the fact that men's generally unrestricted sexual strategies, plus their social
      competitiveness, motivate them to participate in drinking games to display their
      fortitude and compete with same-sex rivals. Here, the authors conducted a study
      to evaluate with greater causal rigor whether sex differences in sexual
      restrictedness and social competitiveness-and sex differences in motivations for
      participating in drinking games in particular-are partially responsible for the
      sex differences in university students' drinking game behaviors and drinking
      problems. Sex differences in changes in frequency of drinking game participation
      were partially mediated by competitive motivations for participating in drinking
      games and by the effects of social competitiveness on competitive drinking game
      motivation. These findings lend additional support to the proposition that
      participation in drinking games is motivated in part by their suitability as a
      venue for sexual competition in university students' day-to-day lives.

PMID- 25974962
TI  - Serial casting for reconstruction of a deformed Charcot foot: a case report.
AB  - INTRODUCTION: Charcot neuroarthropathy may occur in patients with peripheral
      neuropathy who do not notice pain while their bones and joints collapse or
      breakdown under the constant pressure of body weight. This can lead to
      ulcerations from severe deformity and potentially limb-threatening and life
      threatening infections. Current treatments vary from immobilization to extensive
      reconstructive surgical interventions. METHODS: Serial casting, used to correct
      many pediatric deformities while bones are often more pliable, was used with a 63
      year-old male patient who presented with an active phase of Charcot foot with
      ulceration. The patient previously underwent foot reconstruction and had all
      hardware removed prior to serial casting. Due to the potential pliability of the
      bones, serial casting was attempted to reform the shape and position of the foot
      in a reverse Ponseti-type serial casting to create a more stable structure with
      less deformity that could lead to epithelial breakdown. RESULTS: The patient
      regained full ambulation with a plantargrade foot and no wounds, and was followed
      without complications for 36 months. CONCLUSION: Serial weekly casting was an
      effective modality for treatment of this patient's Charcot foot deformity.

PMID- 25974963
TI  - YM155 potently triggers cell death in breast cancer cells through an autophagy-NF
      kB network.
AB  - Specific overexpression in cancer cells and evidence of oncogenic functions make
      Survivin an attractive target in cancer therapy. The small molecule compound
      YM155 has been described as the first "Survivin suppressant" but molecular
      mechanisms involved in its biological activity and its clinical potential remain
      obscure. We herein show that YM155 exerts single agent toxicity on primary breast
      cancer cells grown in an ex vivo assay preserving tumor microenvironment. In
      vitro assays indicate that YM155 more efficiently triggers cell death in breast
      cancer cells (including these with stem-cell like properties) than in non
      tumorigenic mammary cells. YM155-induced cell death is critically dependent on
      autophagy and NF-kB but independent of p53 and it coincides with DNA damage and a
      DNA damage response in p53-proficient cells. Our results point out a crosstalk
      between NF-kB and autophagy controlling YM155-induced death in breast cancer
      cells and argue for the potential use of YM155 as a genotoxic agent in breast
      cancer therapy. 

PMID- 25974964
TI  - Histone demethylase RBP2 promotes malignant progression of gastric cancer through
      TGF-beta1-(p-Smad3)-RBP2-E-cadherin-Smad3 feedback circuit.
AB  - Some feedback pathways are critical in the process of tumor development or
      malignant progression. However the mechanisms through which these pathways are
      epigenetically regulated have not been fully elucidated. Here, we demonstrated
      that the histone demethylase RBP2 was crucial for TGF-beta1-(p-Smad3)-RBP2-E
      cadherin-Smad3 feedback circuit that was implicated in malignant progression of
      tumors and its knockdown significantly inhibited gastric cancer (GC) metastasis
      both in vitro and in vivo. Mechanistically, RBP2 can directly bind to E-cadherin
      promoter and suppress its expression, facilitating EMT and distant metastasis of
      GC. RBP2 can also be induced by TGF-beta1, a key inducer of EMT, through
      phosphorylated Smad3 (p-Smad3) pathway in GC. The upregulated RBP2 can be
      recruited by p-smad3 to E-cadherin promoter and enhance its suppression,
      contributing to the promotion of metastasis of GC. In addition, the suppression
      of E-cadherin by RBP2 attenuated inhibition of Smad3 phosphorylation (exerted by
      E-cadherin), resulting further induction of RBP2 expression, and thus
      constituting positive feedback regulation during GC malignant progression. This
      TGF-beta1-(p-Smad3)-RBP2-E-cadherin-Smad3 feedback circuit may be a novel
      mechanism for GC malignant progression and suppression of RBP2 expression may
      serve as a new strategy for the prevention of tumor distant metastasis.

PMID- 25974965
TI  - UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated
      restriction of NF-kappaB activity.
AB  - The importance of stress-induced p53 activation has been extensively investigated
      and well established. How the basal activity of p53 prevents carcinogenesis,
      however, remains incompletely understood. We report the identification of a novel
      p53 inhibitor, UXT, which binds to MDMX and suppresses the basal activity of p53.
      Interestingly, human TCGA database indicates that the UXT gene is frequently
      amplified in human sarcoma where p53 mutation is rare. We thus used sarcoma as a
      model to show that UXT acts as an oncogene promoting cell proliferation in vitro
      and tumor progression in vivo. A screening of 10 major cellular pathways
      uncovered that UXT-mediated p53 inhibition results in an activation of NF-kappaB,
      leading to induction of glycolysis. While elevated glycolytic metabolism provides
      growth advantage it also renders UXT expressing sarcoma cells heightened
      sensitivity to glycolysis inhibition. Altogether, our data demonstrate a crucial
      role for the basal activity of p53 in restriction of NF-kappaB. By impeding such
      an activity of p53, UXT unleashes the oncogenic activity of NF-kappaB resulting
      in induction of glycolysis fueling carcinogenesis.

PMID- 25974967
TI  - Intermediate and near visual acuity of an aspheric, bifocal, diffractive
      multifocal intraocular lens with +3.25 D near addition.
AB  - PURPOSE: To evaluate the clinical outcomes after cataract surgery with
      implantation of a new diffractive multifocal intraocular lens with a lower near
      addition. METHODS: A prospective multicenter clinical study including 44 eyes of
      44 patients (age range: 43 to 82 years) that underwent cataract surgery with
      implantation of the Tecnis ZLB00 multifocal intraocular lens (Abbott Medical
      Optics, Santa Ana, CA). Changes in uncorrected and corrected distance,
      intermediate, and near visual acuity, and manifest refraction were evaluated
      during a 3-month follow-up. Additionally, patients were asked about photic
      phenomena and spectacle dependence. RESULTS: Postoperative spherical equivalent
      was within 0.50 and +/- 1.00 diopters of emmetropia in 91.2% and 100% of eyes,
      respectively. Postoperative monocular uncorrected distance, near, and
      intermediate visual acuities were 0.10 logMAR (20/25 Snellen) or better in 82.5%,
      86.5%, and 68.8% of eyes, respectively. All eyes achieved monocular corrected
      distance and near visual acuity of 0.10 logMAR (20/25 Snellen) or better. All
      patients reported to be satisfied with the outcomes of the surgery. Only 6
      patients (13.6%) required the use of spectacles for some daily activities
      postoperatively, and 8 patients (18.2%) reported mild perception of halos.
      CONCLUSIONS: The introduction of low addition multifocal intraocular lenses
      follows a trend to increase intermediate visual acuity. Still, a near addition of
      +3.25 diopters reached satisfying near results and led to high patient
      satisfaction.

PMID- 25974966
TI  - Induced inflammation and apoptosis in femtosecond laser-assisted capsulotomies
      and manual capsulorhexes: an immunohistochemical study.
AB  - PURPOSE: To evaluate cellular inflammation and apoptosis induced in the central
      portion of capsulorhexes/capsulotomies during cataract surgery, comparing a
      conventional manual technique and a femtosecond laser-assisted procedure at
      different energy settings using two laser systems. METHODS: Fifty-six
      capsulorhexes/capsulotomies were divided into four groups: the manual group (14
      capsulorhexes) performed with the manual technique; the 7.0-uJ group (14
      capsulotomies) (LensAR laser system; Lensar, Inc., Orlando, FL); the 10-uJ group
      (14 capsulotomies) (LenSx laser system; Alcon Laboratories, Inc., Fort Worth,
      TX); and the 13.0-uJ group (14 capsulotomies) (LenSx laser system). All samples
      were stained for cellular apoptosis analysis (TUNEL assay) and cellular induced
      inflammation (NF-kappaB). RESULTS: One-way analysis of variance indicated a
      statistically significant difference in the percentage of NF-kappaB and TUNEL
      positive cells between the four groups, (F [3.52] = 14.717, P < .001) and (F
      [3.52] = 139.561, P < .001), respectively. Post-hoc analysis indicated a
      statistically significant difference in the percentage of NF-kappaB positive
      cells between the 13.0-uJ group and the manual, 7.0-uJ, and 10-uJ groups (P <
      .001, = .037, and < .001, respectively). Post-hoc analysis of differences in
      TUNEL positive cells indicated a significant difference between the 7.0-uJ and 10
      uJ groups (P <.017) and between the 13.0-uJ group and the manual, 7.0-uJ, and 10
      uJ groups (P < .001, < .001, and < .001, respectively). CONCLUSION: The results
      show a higher percentage of NF-kappaB and TUNEL positive cells in the 13.0-uJ
      group compared to the 7.0-uJ, 10-uJ, and manual groups. Therefore, inflammatory
      response and cell death increased at increasing energies. An effective
      capsulotomy in femtosecond laser-assisted cataract surgery with minimal
      detrimental apoptotic and inflammatory effects is possible if the laser system is
      set to use the minimum energy level.

PMID- 25974968
TI  - Correlating optical bench performance with clinical defocus curves in varifocal
      and trifocal intraocular lenses.
AB  - PURPOSE: To investigate the correlations existing between a trifocal intraocular
      lens (IOL) and a varifocal IOL using the "ex vivo" optical bench through-focus
      image quality analysis and the clinical visual performance in real patients by
      study of the defocus curves. METHODS: This prospective, consecutive,
      nonrandomized, comparative study included a total of 64 eyes of 42 patients.
      Three groups of eyes were differentiated according to the IOL implanted: 22 eyes
      implanted with the varifocal Lentis Mplus LS-313 IOL (Oculentis GmbH, Berlin,
      Germany); 22 eyes implanted with the trifocal FineVision IOL (Physiol, Liege,
      Belgium), and 20 eyes implanted with the monofocal Acrysof SA60AT IOL (Alcon
      Laboratories, Inc., Fort Worth, TX). Visual outcomes and defocus curve were
      evaluated postoperatively. Optical bench through-focus performance was quantified
      by computing an image quality metric and the cross-correlation coefficient
      between an unaberrated reference image and captured retinal images from a model
      eye with a 3.0-mm artificial pupil. RESULTS: Statistically significant
      differences among defocus curves of different IOLs were detected for the levels
      of defocus from -4.00 to -1.00 diopters (D) (P < .01). Significant correlations
      were found between the optical bench image quality metric results and logMAR
      visual acuity scale in all groups (Lentis Mplus group: r = -0.97, P < .01;
      FineVision group: r = -0.82, P < .01; Acrys of group: r = -0.99, P < .01). Linear
      predicting models were obtained. CONCLUSIONS: Significant correlations were found
      between logMAR visual acuity and image quality metric for the multifocal and
      monofocal IOLs analyzed. This finding enables surgeons to predict visual outcomes
      from the optical bench analysis.

PMID- 25974969
TI  - Long-term visual function and patient satisfaction after bilateral implantation
      and combination of two similar multifocal IOLs.
AB  - PURPOSE: To evaluate the visual outcome, spectacle independence, and patient
      satisfaction after implantation of two Acrysof ReSTOR (Alcon Laboratories, Inc.,
      Fort Worth, TX) intraocular lenses (IOLs) with different addition power or their
      combination in both eyes. METHODS: One hundred twenty eyes of 60 patients with
      bilateral multifocal IOL implantation were divided into three groups of 20
      consecutive patients each: the SV25T0 (the T0 group), the SN6AD1 (the D1 group),
      or a combination of both the SN6AD1 and SV25T0 (the combined group). Patients
      were observed 18 months postoperatively for visual acuity (40, 50, and 60 cm, and
      4 m), defocus curves (range: +1.0 to -4.0 diopters), and contrast sensitivity.
      Quality of vision, patient satisfaction, and spectacle independence were
      evaluated by the National Eye Institute Refractive Error Quality of Life
      Instrument-42 questionnaire. RESULTS: The D1 group achieved better results for
      near vision (P < .01), whereas the T0 group achieved better intermediate vision
      (P = .01). The combined group showed a wider range of spectacle independence at
      all distances evaluated (P < .05). The contrast sensitivity was similar within
      the groups. The incidence of glare was lower for the T0 group (P = .054). The
      combined group had better results in terms of expectation (P = .021) and activity
      limitation (P = .003). CONCLUSION: Although the bilateral implantation of the
      same multifocal IOL can maximize the vision for near or intermediate distances,
      the combination of these IOLs in both eyes can increase the range of spectacle
      independence without compromising the contrast sensitivity and quality of vision.

PMID- 25974970
TI  - Outcomes for Myopic LASIK With the MEL 90 excimer laser.
AB  - PURPOSE: To evaluate the visual outcomes of myopic LASIK performed with the MEL
      90 excimer laser (Carl Zeiss Meditec AG, Jena, Germany) using the Triple-A
      profile with a 500-Hz pulse rate. METHODS: Retrospective analysis of the first
      286 myopic LASIK procedures (147 patients) by two experienced surgeons in which
      the VisuMax femtosecond laser and MEL 90 excimer laser (Carl Zeiss Meditec) were
      used following a standardized surgical technique. Inclusion criteria were
      preoperative spherical equivalent refraction (SEQ) up to -10.38 diopters (D),
      cylinder up to 5.00 D, and corrected distance visual acuity (CDVA) of 20/25 or
      better. No nomogram adjustments were made. Patients were observed for 3 months.
      Flap thickness was between 80 and 110 um and optical zone was between 6 and 7 mm.
      Standard outcomes analysis was performed. RESULTS: Preoperatively, mean SEQ was 
      3.83 +/- 1.83 D (range: -0.13 to -10.38 D) and mean cylinder was -0.94 +/- 0.86 D
      (range: 0.00 to -5.00 D). Mean age was 36.4 years (range: 18.2 to 74.1 years)
      with 50% female patients. Of this population, 138 eyes were treated by one
      surgeon and 148 eyes by another. The mean predictability of SEQ was -0.13 +/-
      0.34 D (range: -1.00 to +1.00 D). Postoperative SEQ was +/- 0.50 D in 88% and +/-
      1.00 D in 100% of eyes. Preoperative CDVA was 20/20 or better in 97% of eyes.
      Postoperative uncorrected distance visual acuity was 20/20 or better in 92% and
      20/25 or better in 99% of eyes. One line of CDVA was lost in 6% of eyes and no
      eyes lost two or more lines. There was statistically significant improvement in
      mesopic contrast sensitivity (CSV-1000) at 3 (P = .021), 6, 12, and 18 (all P
      <=.001) cycles per degree. CONCLUSIONS: The MEL 90 excimer laser using the Triple
      A ablation profile with a 500-Hz pulse rate was found to achieve a small but real
      increase in contrast sensitivity and high efficacy for myopia up to -10.00 D and
      cylinder up to 5.00 D without the need for a nomogram adjustment.

PMID- 25974971
TI  - Vector analysis of 1-year astigmatic outcomes from a prospective, randomized,
      fellow eye comparison of wavefront-guided and wavefront-optimized LASIK in
      myopes.
AB  - PURPOSE: To compare the astigmatic outcomes of LASIK with a single excimer laser
      platform using either wavefront-guided (WFG) or wavefront-optimized (WFO) modes.
      METHODS: Sixty-eight eyes of 34 patients underwent LASIK for myopia with the
      Wavelight Allegretto Eye-Q 400-Hz laser platform (Alcon Laboratories, Inc.,
      Huenberg, Switzerland). One eye underwent WFG-LASIK and the contralateral eye
      underwent WFO-LASIK. Alpins vector analysis of astigmatism was performed using
      manifest refraction measured preoperatively and 12 months postoperatively and
      vertexed to the corneal plane. Eyes were stratified for subgroup analysis based
      on preoperative manifest astigmatism. RESULTS: WFG-LASIK and WFO-LASIK were
      similar with regard to surgically induced astigmatism, difference vector,
      magnitude of error, correction index, flattening index, and index of success. The
      angle of error was 80% less in the WFG group compared to the WFO group (1.92
      degrees  +/- 0.67o vs 9.66 degrees  +/- 3.7o, P = .04). CONCLUSIONS: WFG-LASIK
      and WFO-LASIK using the Alcon WaveLight Allegretto Eye-Q 400-Hz excimer laser
      platform produce similar astigmatic results in myopic patients; however, the WFG
      mode may produce slightly more predictable astigmatic corrections.

PMID- 25974972
TI  - Comparison of pachymetry measurements between the Alcon Wavelight EX500 and
      Sonogage Corneo-Gage plus platforms.
AB  - PURPOSE: To compare the agreement of intraoperative central corneal thickness
      (CCT) measurements of the Wavelight EX500 (Alcon Laboratories, Fort Worth, TX)
      that uses optical low coherence reflectometry to the Corneo-Gage Plus ultrasound
      pachymetry device (Sonogage, Cleveland, OH). METHODS: In this retrospective
      study, 50 eyes of 26 patients undergoing LASIK were evaluated. Following LASIK
      flap creation, each eye was measured by both optical low coherence reflectometry
      and ultrasound pachymetry immediately prior to flap lifting and then again after
      flap lifting. RESULTS: The mean CCT value before lifting the flap was 556.9 and
      557.78 um as measured by ultrasound pachymetry and optical low coherence
      reflectometry, respectively. After lifting the flap, the mean ultrasound
      pachymetry value was 440.96 um and the mean optical low coherence reflectometry
      value was 441.7 um. A two-sample Kolmogorov-Smirnov test demonstrated that the
      ultrasound pachymetry and the optical low coherence reflectometry distribution of
      measurements were the same. A Shapiro-Wilk test of normality could not be
      rejected. Bland-Altman plots showed strong agreement. The correlation between the
      two tests was 0.98 before flap lifting and 0.97 after flap lifting, both with a
      95% confidence interval. CONCLUSIONS: The pachymetry measurements by the optical
      low coherence reflectometry correlated with those of the ultrasound pachymetry
      device. The Wavelight EX500 optical low coherence reflectometry may be used in
      place of the ultrasound pachymetry device for measuring CCT.

PMID- 25974973
TI  - Repeatability data and agreement of keratometry with the VERION system compared
      to the IOLMaster.
AB  - PURPOSE: To analyze the repeatability of keratometric and white-to-white (WTW)
      distance measurements with the VERION Measurement Module (Alcon Laboratories,
      Inc., Fort Worth, TX) and to compare the measured data to the results of the
      IOLMaster (Carl Zeiss Meditec, Jena, Germany). METHODS: Three images were
      captured with the VERION and the flattest and steepest keratometric data, the
      astigmatism axis, and the WTW distance were recorded. Subsequently, the axial
      length, the keratometric data with axis, and the WTW distance were measured with
      an IOLMaster. The repeatability data of the keratometric value of the VERION
      System, converted to cross cylinder J0 and J45 vector components, were analyzed.
      The agreement data for keratometry obtained by the VERION System and the
      differences regarding keratometric data and WTW distance compared to IOLMaster
      were calculated. RESULTS: The measurements were conducted in 50 eyes of 50
      healthy volunteers (median age: 50.32 years, range: 19.34 to 85.3 years). The
      flattest and the steepest keratometric data, the diopter of astigmatism, the J0
      and J45 vector components, and WTW distance did not differ significantly between
      devices (P > .05). Intraclass correlation coefficients (range: 0.863 to 0.994)
      and Cronbach's alpha values (range: 0.950 to 0.998) were high for all parameters
      measured by the VERION System. CONCLUSIONS: The VERION System has high
      repeatability and agreement with the IOLMaster, making it suitable as an
      alternative tool in clinical practice.

PMID- 25974974
TI  - Femtosecond Laser-assisted Cataract Surgery in Patients With Marfan Syndrome and
      Subluxated Lens.
AB  - PURPOSE: To report femtosecond laser-assisted cataract surgeries in patients with
      Marfan syndrome with mild, moderate, and severe lens subluxation. METHODS: Case
      reports. RESULTS: Two patients with Marfan syndrome underwent femtosecond laser
      assisted cataract surgery (Alcon LenSx Lasers Inc., Aliso Viejo, CA). One patient
      had a mild lens subluxation in one eye and a moderate lens subluxation in the
      fellow eye. The other patient had a severe lens subluxation in one eye. In all
      eyes, the laser was able to perform a circular and free-floating anterior
      capsulotomy and lens fragmentation. In two of the eyes it was also helpful in
      decreasing corneal astigmatism by making corneal intrastromal relaxing incisions.
      There were no postoperative complications. CONCLUSIONS: Femtosecond laser
      assisted cataract surgery is an effective approach for cataract surgery in
      patients with Marfan syndrome with mild, moderate, and even severe lens
      subluxation, with the benefits of causing minimal further zonular damage and
      being able to treat corneal astigmatism with relaxing incisions.

PMID- 25974976
TI  - Bladeless custom femtosecond laser-assisted refractive cataract surgery? let's
      give our latest breakthrough surgical technique a name that fits.

PMID- 25974975
TI  - LASIK flap breakthrough in Nd:YAG laser treatment of epithelial ingrowth.
AB  - PURPOSE: To present two cases with complications after Nd:YAG laser treatment of
      epithelial ingrowth. METHODS: Case reports. RESULTS: Dense central recurrent
      epithelial ingrowth was treated with a Nd:YAG laser directed at the epithelial
      nests in the LASIK flap interface in one case. Misalignment of the aiming beam
      after movement resulted in perforation of the LASIK flap, followed by renewed
      epithelial ingrowth through the new defect. The epithelial ingrowth receded and
      became more translucent as a result of the treatment, but the area of the
      perforation remained irregular. In another case, use of the Nd:YAG laser to treat
      recurrent epithelial ingrowth adjacent to the flap edge created a cavitation
      bubble that broke through the flap edge, creating a new epithelial channel
      through which ingrowth recurred. CONCLUSIONS: Surface breakthrough and renewed
      epithelial ingrowth is a possible complication of Nd:YAG laser treatment of
      epithelial ingrowth.

PMID- 25974977
TI  - Combined posterior phakic intraocular lens and SMILE in a patient with high
      myopia.

PMID- 25974978
TI  - Surgically induced astigmatism: distinguishing between dioptric vectors and non
      vectors.

PMID- 25974979
TI  - Targeted delivery of 5-aminolevulinic acid by multifunctional hollow mesoporous
      silica nanoparticles for photodynamic skin cancer therapy.
AB  - 5-Aminolevulinic acid (5-ALA) is a precursor of a strong photosensitizer,
      protoporphyrin IX (PphIX), for photodynamic therapy (PDT). Developing appropriate
      delivery carriers that can assist 5-ALA in bypassing the lipophilic barrier to
      directly enter into cancer cells is a research focus. The improved delivery of 5
      ALA is even important for skin cancer therapy through PDT process. In this work,
      targeting ligand folic acid (FA)-functionalized hollow mesoporous silica
      nanoparticles (HMSNPs) were fabricated to deliver 5-ALA for PDT against B16F10
      skin cancer cells. The FA targeting ligand enabled selective endocytosis of 5-ALA
      loaded HMSNPs into cancer cells. PphIX formed from delivered 5-ALA exhibited high
      photocytotoxicity to the cancer cells in vitro. 

PMID- 25974980
TI  - Highly Efficient FRET System Capable of Deep Photodynamic Therapy Established on
      X-ray Excited Mesoporous LaF3:Tb Scintillating Nanoparticles.
AB  - Photodynamic therapy (PDT) for deep-seated tumor is largely impeded by the
      limited penetration depth of excitation light in tissue. X-ray is considered as
      an ideal energy source to activate photosensitizers (PSs) located deep within the
      body with the assistance of scintillating nanoparticles (ScNPs). However, the
      efficacy under this concept is not satisfying due to the low scintillating
      luminescence and weak energy transfer from ScNPs to PSs. Here, mesoporous LaF3:Tb
      ScNPs were successfully synthesized by a facile hydrothermal process to act as PS
      carriers and X-ray energy transducers, owing to their good ionizing radiation
      stopping power and high luminescence efficiency. The formation mechanism of
      porous structure was elucidated in detail with classical crystallization theory.
      After a systematic investigation, LaF3:Tb ScNPs with optimized scintillating
      luminescence were obtained for loading Rose Bengal (RB) to establish an efficient
      FRET system, owing to their excellent spectral match. The FRET efficiency between
      ScNPs and RB was calculated to be as high as 85%. Under irradiation, enhanced
      (1)O2 generation induced by LaF3:Tb-RB nanocomposites via FRET process was
      detected. This LaF3:Tb-RB FRET system shows great potential to be applied in X
      ray stimulated PDT for deep-seated tumors in the future. 

PMID- 25974982
TI  - How I do it: monthly quality review - the tools I use.

PMID- 25974981
TI  - [Strong and tunable field enhancement obtained by periodic rectangular pit
      structure].
AB  - The authors have designed a novel type of periodic rectangular pit nanostructure
      substrate based on the surface plasmon principle. Finite element method was
      employed to simulate the optical near-field distribution. Strongly enhanced field
      whose electric intensity Emax/E0 can be as high as 20 at resonance frequency
      appears around pithead of the periodic structure. As the period of structure, pit
      length l, width w and environment change, the authors observe the regular
      shifting of plasmon resonant wavelength which can cover the range from 500 to
      1000 nm. The red shifts of SPR resonance peaks are increased with the increment
      of period Px when incident light is polarized along x axis. An abrupt decrease in
      localized electric field in the pit is observed as incident wavelength approaches
      Px. This is due to the satisfaction of wave vector matching condition and the
      excitation of propagating SPP. SPR resonance peaks also red shifts with the
      increment on pit length l and environment dielectric refractive index, presenting
      a linear dependence with pit length l. While the resonance peaks are blue shifted
      with the increment of pit width w. The results presented in this paper will
      provide a way to tune the plasmon resonant wavelength. Inspired by Jain's report,
      SPR resonance peaks' shifting with the changing of structure parameters can be
      explained by viewing the rectangular pit nanostructure as combination of two
      pairs of dipole-dipole coupling models along x and y axis respectively.

PMID- 25974983
TI  - Raising the bar: when hope vanishes.

PMID- 25974984
TI  - Podcasts, blogs, websites, and public libraries: non-traditional research
      resources for scientists and clinicians.

PMID- 25974985
TI  - Flow cytometric study of cell cycle and DNA ploidy in bilharzial bladder cancer.
AB  - BACKGROUND: Tumor grade and stage are currently the most important prognostic
      variables in bladder cancer but establishing additional criteria is still needed
      for effective treatment. In this study, we analyzed DNA ploidy and the cell
      cycle: gap one stage (GO/1), synthesis stage (S-phase%), and gap two stage (G2/M)
      in urine and blood cells of bilharzial bladder cancer patients. METHODS: The cell
      cycle and DNA ploidy were investigated using a flow cytometric technique for 150
      bilharzial bladder cancer patients and 60 healthy normal controls. RESULTS: This
      study demonstrated that GO/1 levels were significantly decreased in urine and
      blood cells of bladder cancer patients compared to controls and these decreases
      were significant in urine cells compared to blood cells and at high grade and
      stage. In contrast, S-phase%, G2/M, coefficient variation (CV), and DNA index
      (DI) levels were increased in urine and blood cells of patients compared to those
      of controls. These levels were significantly increased in urine patients compared
      to their blood. Finally, the undetectable DNA aneuploidy in control cells was
      significantly increased in urine cells of patients compared to their blood cells
      at higher grade and stage. CONCLUSIONS: Taken together, the cell cycle and DNA
      aneuploidy analysis especially in urine cells of bilharzial bladder cancer
      patients may help in diagnosis, prognosis, and clinical treatment and can be
      considered as an additional marker for bladder cancer.

PMID- 25974986
TI  - Etiological role of ortho- and paramyxoviruses in acute respiratory tract
      infections among children aged < 4 years in Bulgaria.
AB  - BACKGROUND: Influenza viruses (family Orthomyxoviridae); respiratory-syncytial
      virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (hPIV) type
      1, 2 and 3 (family Paramyxoviridae) are among the most common causes of acute
      respiratory tract infections (ARTI) in infants and young children. The aim of
      this study was to determine the contribution of these viruses in cases of ARTI
      requiring medical attention among children aged < 4 years during the 2012/13 and
      2013/14 winter seasons in Bulgaria. METHODS: A total of 416 nasopharyngeal swabs
      of children aged < 4 years presenting ARTI from different regions of country were
      tested for influenza A/B viruses by real-time RT-PCR. Influenza virus negative
      samples were examined by individual real-time RT-PCR using specific
      primers/probes for RSV, hMPV, and hPIV1, 2, and 3. RESULTS: Of the 416 specimens
      tested, 129 (31%) were influenza virus positive. Influenza A(H1N1)pdm09, A(H3N2),
      and type B viruses were found in 61 (14.7%), 14 (3.4%), and 49 (11.8%) of
      samples, respectively. Of the 287 influenza virus negative specimens,
      paramyxoviruses - RSV, hMPV, hPIV1, hPIV2, and hPIV3 were detected in 55 (19.2%),
      28 (9.8%), 17 (5.9%), 5 (1.7%), and 14 (4.9%) samples, respectively. RSV were the
      most frequently identified paramyxovirus (p < 0.05). Overall, 15 (6.4%) patients
      were co-infected with two viruses. The contribution of respiratory viruses in
      cases of bronchiolitis, pneumonia, and neurological complications was analyzed.
      CONCLUSIONS: Influenza viruses and RSV were the most frequent viral pathogens
      causing ARTI among children < 4 years of age during the 2012/13 and 2013/14
      winter seasons in Bulgaria.

PMID- 25974988
TI  - Detection and quantification of hypo- and hypergranulated neutrophils on the new
      Sysmex XN hematology analyzer: establishment of an adapted reference interval for
      the neutrophil-granularity-intensity compared to XE-technology in adult patients.
AB  - BACKGROUND: Since the recent introduction of Sysmex hematology analyzers of the
      XN-series it can be expected that the values of individual hematological
      parameters might differ between the new XN and the well-established XE platform.
      One such parameter is called Neutrophil-Granularity-Intensity or NEUT-GI on the
      XN-series and NEUT-X on the XE-series. Both parameters are used by clinicians to
      calculate the Granularity-Index (GI-Index), an important tool to detect hypo- or
      hypergranulated neutrophils occurring during myelodysplasia or inflammation. The
      aims of this study were to determine if previously reported reference intervals
      for NEUT-X can be used for NEUT-GI as well and if the GI-Indices on both analyzer
      platforms correlate with each other. METHODS: NEUT-GI and NEUT-X were assessed in
      a set of 789 blood samples (n = 543 samples from adult intensive care units and n
      = 246 samples from adult "blood-healthy" control patients) and the corresponding
      Granularity-Indices were calculated for all samples using data obtained from XE
      5000 and XN-1000 hematology analyzers. RESULTS: NEUT-GI and NEUT-X correlated
      significantly with each other (r2: 0.6512; p < 0.0001) with statistically
      significant higher values for NEUT-GI compared to NEUT-X in the control group (p
      < 0.0001) as well as in the ICU patients (p < 0.0001). This indicated that
      previously established reference intervals for NEUT-X cannot be used for NEUT-GI.
      In contrast, the GI-Indices showed no statistically significant difference
      between the analyzers in both groups. The GI-Indices were higher in the ICU
      patients compared to the control group on both analyzer platforms (p < 0.0001),
      as would be expected. CONCLUSIONS: Our study revealed the emphatic need for a new
      reference interval for NEUT-GI on the XN platform. The resulting 95% reference
      intervals were 140.91 - 160.46 channels for NEUT-GI and 129.20 - 142.33 channels
      for NEUT-X. The GI-Indices showed no significant statistical difference between
      the XN- and XE-series in both cohorts.

PMID- 25974987
TI  - A novel COL10A1 mutation in a Chinese pedigree with Schmid type metaphyseal
      chondrodysplasia.
AB  - BACKGROUND: Schmid type metaphyseal chondrodysplasia (MCDS) is a kind of
      autosomal inherited epiphyseal dysplasia caused by a mutation of the COL10A1
      gene. Clinical expression of this mutation includes a waddling gait, coxa vara,
      genu varus or genu valgus and shortened lower limbs among others. To date, over
      40 kinds of heterozygous mutations have been identified in the collagen domain of
      COL10A1 but data on family pedigrees for these is lacking. METHODS: Nineteen
      people without a history of interbreeding were selected for the three generations
      pedigree of MCDS. The proband is a 13 year-old boy with short limbs, hip varus,
      and tibial varus. In this group, seven people had MCDS (two men, five women).
      Blood samples for DNA extraction and mutational analysis were collected to
      sequence the CLO10A1 gene. RESULTS: Chromas atlas analysis and monoclonal
      sequencing revealed that 7 of the patients in the family are missing a C
      nucleotide in the third exon of the COL10A1 gene (c.2005delC). CONCLUSIONS: The
      COL10A1 gene mutation results in a frameshift mutation from codon 669, the
      substitution of 7 amino acids, and premature termination of expression
      (p.his669thrfsX8). In contrast to the other mutations identified, c.2005delC is
      close to the C-terminus of the protein sequence and may result in genetic
      heterogeneity of the Chinese population.

PMID- 25974989
TI  - Decreased local and systematic matrix Gla protein (MGP) expression and its link
      to radiographic progression in ankylosing spondylitis patients.
AB  - BACKGROUND: Decreased serum levels of uncarboxylated matrix Gla-protein (ucMGP)
      have been detected in Ankylosing Spondylitis (AS) patients. The current study was
      to investigate the expression of MGP in AS tissues as well as the relationship
      between serum ucMGP (an inactive form of MGP) levels and radiographic severity in
      AS patients. METHODS: Local MGP expression were assessed by Western blot and RT
      PCR in hip synovial tissues from patients with AS and control subjects. In
      addition, the serum level of ucMGP was assessed by enzyme-linked immunosorbent
      assay in 68 healthy subjects and 62 patients with AS. The radiographic
      progression of AS was classified according to the radiographic events of modified
      New York Criteria for sacroiliac joint evaluation and modified Stoke Ankylosing
      Spondylitis Spine Score (mSASSS) system for spine assessment. RESULTS: MGP
      expression was downregulated in AS patients compared to controls in hip tissues.
      Decreased levels of ucMGP in serum were found in AS patients compared with
      healthy controls. ucMGP levels in serum of AS patients were significantly
      negatively correlated with the disease radiographic severity evaluated by
      modified New York grading criteria (r = -0.293, p = 0.045) and mSASSS system (r =
      -0.361, p = 0.03). CONCLUSIONS: MGP expression is impaired in patients with AS. A
      low serum level of ucMGP in the setting of AS is linked to increased structural
      damage, emphasizing the role of MGP in the suppression of new bone formation.

PMID- 25974990
TI  - The use of reference change values in clinical laboratories.
AB  - BACKGROUND: The use of Reference Change Values (RCV) has been advocated as very
      useful for monitoring individuals. Most of these are performed for monitoring
      individuals in acute situations and for following up the improvement or
      deterioration of chronic diseases. In our study, we aimed at evaluating the RCV
      calculation for 24 clinical chemistry analytes widely used in clinical
      laboratories and the utilization of this data. METHODS: Twenty-four serum samples
      were analyzed with Abbott kits (Abbott Laboratories, Abbott Park, IL, USA),
      manufactured for use with the Architect c8000 (Abbott Laboratories, Abbott Park,
      IL, USA) auto-analyzer. We calculated RCV using the following formula: RCV = Z x
      2 1/2x (CVA2 + CVw2)1/2. Four reference change values (RCV) were calculated for
      each analyte using four statistical probabilities (0.95, and 0.99, unidirectional
      and bidirectional). Moreover, by providing an interval after identifying upper
      and lower limits with the Reference Change Factor (RCF), serially measured tests
      were calculated by using two formulas: exp (Z x 2 1/2 x (CV(A)2 + CVw2)1/2/100)
      for RCF(UP) and (1/RCF(UP)) for RCF(DOWN). RESULTS: RCVs of these analytes were
      calculated as 14.63% for glucose, 29.88% for urea, 17.75% for ALP, 53.39% for CK,
      46.98% for CK-MB, 21.00% amylase, 8.00% for total protein, 8.70% for albumin,
      51.08% for total bilirubin, 86.34% for direct bilirubin, 6.40% for calcium,
      15.03% for creatinine, 21.47% for urate, 14.19% for total cholesterol, 46.62% for
      triglyceride, 20.51% for HDL-cholesterol, 29.59% for AST, 46.31% for ALT, 31.54%
      for GGT, 20.92% for LDH, 19.75% for inorganic phosphate, 3.05% for sodium, 11.75%
      for potassium, 4.44% for chloride (RCV, p < 0.05, unidirectionally). CONCLUSIONS:
      We suggest using RCV as well as using population-based reference intervals in
      clinical laboratories. RCV could be available as a tool for making clinical
      decision, especially when monitoring individuals.

PMID- 25974991
TI  - Anti-mutated citrullinated vimentin antibody and rheumatoid factor (prevalence
      and association) in rheumatoid arthritis patients; Saudi and non-Saudi.
AB  - background: The aims of this study were to assess the prevalence of anti-mutated
      citrullinated vimentin (MCV) antibodies and rheumatoid factor (RF) and to
      evaluate their association in rheumatoid arthritis patients, both Saudi and non
      Saudi. METHODS: Retrospectively, we studied 280 rheumatoid arthritis patients, at
      King Abdulaziz University Hospital. The antibodies were measured by enzyme linked
      immunosorbent assay and rheumatoid factor by nephelometry. RESULTS: The 280
      patients included 196 Saudis and 84 non-Saudis, 88% females and 12% males, and
      the mean age was 45.3 years (SD = 14.3). Prevalence of rheumatoid factor was
      141/280 (50%) divided as 93/196 (47.5%) Saudis and 48/84 (57%) non-Saudis, with
      no significant differences (p > 0.05). Prevalence of mutated citrullinated
      vimentin antibodies was 165/280 (58.2%) divided as 121/196 (61.7%) Saudis and
      44/84 (52.4%) non-Saudis, with no significant differences (p > 0.05). Among RF 
      ve patients, considerable numbers were anti-MCV +ve, and vice versa. Also, among
      the anti-MCV -ve patients, considerable numbers were RF +ve, and vice versa. In
      all cohorts and in Saudi and non Saudi patients, anti-MCV positivity was
      significantly associated with RF positivity (odds ratio (OR) 3.15; 95% CI 1.9,
      5.19/p = 0.000); ESR and CRP were high with significant correlation (p < 0.005)
      with each other, with RF positivity but not with anti-MC positivity. Anti-MC
      positivity showed no significant correlation with age and gender. CONCLUSIONS: In
      this cohort of patients, anti-MCV antibodies are a useful diagnostic tool for RA,
      but its combination with RF is essential. Both markers are significantly
      associated. Larger scale studies are recommended. Correlation of anti-MCV with
      treatment and with disease activity still has to be published.

PMID- 25974992
TI  - Neutrophil- and platelet-to-lymphocyte ratios are correlated with disease
      activity in rheumatoid arthritis.
AB  - BACKGROUND: Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte
      ratio (PLR) are reported to be increased in various inflammation-related
      diseases, but their clinical significance in rheumatoid arthritis (RA) remains
      unclear. The aim of the present study was to explore whether NLR and PLR were
      candidate indices for RA disease-activity assessment. METHODS: The medical
      records of 128 RA patients and 78 healthy individuals were retrospectively
      reviewed. Correlations of NLR and PLR with the disease activity of RA were
      evaluated. RESULTS: NLR and PLR were increased significantly in RA patients. NLR
      was significantly positively correlated with C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), and Disease-Activity Score including 28
      joints (DAS28) in RA patients, while PLR was positively correlated with CRP and
      DAS28, but not with ESR. CONCLUSIONS: Both NLR and PLR values may prove to be
      potential indices for RA disease-activity assessment.

PMID- 25974993
TI  - A new ELISA method for serological diagnosis of Legionella pneumophila: use of
      five purified proteins, FLA, MOMP, MIP, IP, and PILE, as diagnostic antigen.
AB  - BACKGROUND: Legionella pneumophila plays an important role in human infection.
      Commercial ELISA kits commonly used, which take Legionella pneumophila whole-cell
      protein as the coating antigen, often have cross-reactivity among serogroups or
      species. In this study, five Legionella pneumophila proteins FLA, MOMP, MIP, IP,
      and PILE were purified and further applied in serological diagnosis of Legionella
      pneumophila infections compared with R & D Legionella ELISA kits. METHODS: The
      five recombinant plasmids pET-fla, pET-momp, pET-mip, pET-ip, and pET-pile were
      transformed into E. coli BL21 and then induced them with IPTG. The expression
      products were analyzed by SDS-PAGE and purified by affinity chromatography.
      Indirect enzyme-linked immunosorbent assays (ELISAs) were established with the
      five purified proteins FLA, MOMP, MIP, IP, and PILE altogether as the coating
      antigen and tested for the presence of IgG, IgM, and IgA antibody independently
      from 50 positive sera and 40 negative sera, compared with R & D IgG, IgM, and IgA
      Legionella ELISA kits. RESULTS: The FLA protein about 42 kDa in size, the MOMP
      protein about 45 kDa, the MIP protein about 40 kDa, the IP protein about 46 kDa,
      and the PILE protein about 35.7 kDa were separately expressed and purified.
      Compared with R & D IgG, IgM, and IgA Legionella ELISA kit, the outcome of
      indirect ELISAs set up with the five purified proteins showed that for IgG the
      sensitivity was 90.4%, the specificity was 97.4%, the area under ROC curve was
      0.939, the kappa value was 0.865, the 95% confidence interval was 0.883 - 0.995.
      For IgM the sensitivity was 91.8%, the specificity was 95.1%, the area under ROC
      curve was 0.935, the kappa value was 0.866, the 95% confidence interval was 0.876
      - 0.994. For IgA the sensitivity was 93.6%, the specificity was 95.3%, the area
      under ROC curve was 0.945, the kappa value was 0.889, the 95% confidence interval
      was 0.890 - 0.999. CONCLUSIONS: The proteins FLA, MOMP, MIP, IP, and PILE were
      successfully expressed and purified, and they seemed to be suitable coating
      antigens for the serological diagnosis of Legionella pneumophila.

PMID- 25974994
TI  - Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin)
      assay.
AB  - BACKGROUND: Vitamin B12 (cobalamin) is a necessary cofactor in methionine and
      succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as
      30% in the elderly population. Ten to thirty percent of circulating cobalamin is
      bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter
      cells and is therefore considered the bioactive form. The objective of our study
      was to evaluate the analytical performance of a high-throughput, automated holoTC
      assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to
      other available methods. METHODS: Manufacturer-specified limits of blank (LoB),
      detection (LoD), and quantitation (LoQ), imprecision, interference, and linearity
      were evaluated for the ARCHITECT HoloTC assay. Residual de-identified serum
      samples were used to compare the ARCHITECT HoloTC assay with the automated AxSYM
      Active-B12 (Holotranscobalamin) assay (Abbott Diagnostics) and the manual Active
      B12 (Holotranscobalamin) Enzyme Immunoassay (EIA) (Axis-Shield Diagnostics,
      Dundee, Scotland, UK). RESULTS: Manufacturer's claims of LoB, LoD, LoQ,
      imprecision, interference, and linearity to the highest point tested (113.4
      pmol/L) were verified for the ARCHITECT HoloTC assay. Method comparison of the
      ARCHITECT HoloTC to the AxSYM HoloTC produced the following Deming regression
      statistics: (ARCHITECT(HoloTc)) = 0.941 (AxSYM(HoloTC)) + 1.2 pmol/L, S(y/x) =
      6.4, r = 0.947 (n = 98). Comparison to the Active-B12 EIA produced:
      (ARCHITECT(HoloTC)) = 1.105 (EIA(Active-B12)) - 6.8 pmol/L, S(y/x) = 11.0, r =
      0.950 (n = 221). CONCLUSIONS: This assay performed acceptably for LoB, LoD, LoQ,
      imprecision, interference, linearity and method comparison to the predicate
      device (AxSYM). An additional comparison to a manual Active-B12 EIA method
      performed similarly, with minor exceptions. This study determined that the
      ARCHITECT HoloTC assay is suitable for routine clinical use, which provides a
      high-throughput alternative for automated testing of this emerging marker of
      cobalamin deficiency.

PMID- 25974995
TI  - Genetic variation in the hemagglutinin of A(H1N1) 09pdm and A(H3N2) influenza
      viruses in the Beijing area from 2009 to 2014.
AB  - BACKGROUND: A(H1N1) 09pdm and A(H3N2) influenza viruses are the main cause of
      occasional influenza pandemics and seasonal influenza epidemics around the world.
      Unfortunately, the understanding of long-term genetic variation in these viruses
      remains limited. METHODS: In this study, hemagglutinin genes from 90 A(H1N1)
      09pdm and 48 A(H3N2) influenza viruses in the Beijing area from 2009 to 2014 were
      sequenced and analyzed. RESULTS: The hemagglutinin genes in A(H1N1) 09pdm and
      A(H3N2) shared nucleotide similarity that ranged from 93.06% - 99.88% and 98.68% 
      99.29%, respectively, compared with current vaccine strains. 10 and 7 amino acid
      mutations in antigenic sites were identified in these two strains, respectively.
      In addition, a new site 177 glycosylation, which did not exist in previous
      circulating strains, was identified in 3 A(H1N1) 09pdm isolates. CONCLUSIONS:
      This study demonstrated the continued evolution of seasonal influenza viruses in
      the Beijing area, indicating that an update of the vaccine is needed, especially
      for A(H1N1) 09pdm influenza virus.

PMID- 25974996
TI  - Feasible quantitative detection of cytomegalovirus from urine sediment in stem
      cell transplant patients.
AB  - BACKGROUND: Urine is an important source for the detection of infections caused
      by CMV in stem cell transplant patients. Currently, there is no agreement about
      the type of urine specimen. In order to investigate which is the better specimen
      type for quantitative detection of CMV, we compared the results from urine
      supernatant and sediment from the same patients. METHODS: Seventy urine specimens
      were collected from patients with hematological disorders or solid tumors. After
      performing shell vial culture, residual urine specimens were centrifuged. Then,
      10 mL of each urine supernatant and sediment were taken and immediately frozen at
      -70 degrees C. Afterwards, archived urine specimens were thawed at room
      temperature and CMV-quantitative PCR was performed on both the supernatant and
      sediment fraction of urine. The results from each patient were reviewed for CMV
      antigenemia, blood shell vial culture, CMV-IgM or IgG, and clinical symptoms.
      RESULTS: CMV-qPCR results for the urine sediment fraction revealed a significant
      difference (p = 0.012) between the active CMV infection group and the latent CMV
      infection group. In addition, receiver operating characteristic curves for active
      CMV infection revealed that CMV-qPCR using urine sediment produced more accurate
      results than urine supernatant. CONCLUSIONS: These findings suggest that the
      sediment fraction of urine is a more suitable specimen in CMV-qPCR testing.

PMID- 25974997
TI  - Changes of lipin1beta expression in gestational diabetes mellitus.
AB  - BACKGROUND: Lipin1beta is an adipokine proposed to be associated with insulin
      resistance (IR). Pregnancy is a physiologic state of progressive IR. The
      objective of the present study was to investigate the role of lipin1beta in the
      development of GDM. METHODS: A total of 40 pregnant women (22 normal and 18 with
      GDM) who delivered healthy infants at full-term (> 37 weeks gestation) were
      included. The mRNA and protein levels of lipin1beta in adipose tissues were
      determined by real-time RT-PCR and Western-blot. Plasma glucose, lipids, insulin,
      and estradiol (E2) levels were measured routinely at fasting state, and HOMA-IR
      was calculated accordingly. RESULTS: The lipin1beta expression in both mRNA and
      protein levels in SAT and VAT was lower in GDM patients than controls. Lipin1beta
      mRNA in VAT was negatively correlated with BMI (r = -0.505, p < 0.05), FINS (r = 
      0.539, p < 0.05), HOMA-IR (r = -0.574, p < 0.01), TG (r = -0.471, p < 0.05), and
      E2 (r = -0.564, p < 0.01). Lipin1beta mRNA expression in SAT was similar with
      VAT. Lipin1beta mRNA was not correlated with body weight gain or blood pressure.
      These results indicated that the lipin1beta expression in adipose tissues is down
      regulated in patients with GDM. CONCLUSIONS: Lipin1beta might play a role in the
      pathogenesis of insulin resistance in GDM.

PMID- 25974998
TI  - DATS suppresses growth of esophageal squamous cell carcinoma by regulation of
      ERK1/2.
AB  - BACKGROUND: It is well known that garlics contain a large number of organosulfur
      compounds including diallyl trisulfide (DATS), which possess anticancer
      properties. However, the effects of DATS on esophageal squamous cell carcinoma
      (ESCC) growth are still poorly understood. In this study, we investigated the
      effects of DATS on ESCC cell growth in vivo and in vitro, as well as the
      associated signaling pathways. METHODS: Cell proliferation was measured using the
      crystal violet assay. The transwell method was used to evaluate the effect of
      DATS on ESCC cell migration. Also, Western blot was performed to detect the
      activation of ERK1/2 and AKT1 responds to DATS. Finally, the effect of DATS on
      ESCC xenografts in nude mice was also investigated. RESULTS: Our results showed
      that DATS significantly inhibited ESCC cell proliferation in a time- and dose
      dependent manner. DATS time-dependently (p < 0.05) increased phosphorylation of
      ERK1/2, but not AKT1. Suppression of ERK1/2 activation with PD9805 also
      completely blocked DATS-inhibited ESCC cell proliferation. Meanwhile, DATS also
      robustly suppressed ESCC xenograft growth and increased ERK1/2 activation in nude
      mice. CONCLUSIONS: Our finding demonstrated that DATS inhibits the proliferation
      of ESCC cells by activation of ERK1/2 in vitro and in vivo. These findings
      revealed that DATS could be used for therapeutic intervention for human ESCC.

PMID- 25974999
TI  - Soluble receptor of advanced glycation end-products in patients with acute
      myocardial infarction treated with remote ischaemic conditioning.
AB  - BACKGROUND: Several studies have demonstrated that soluble receptor of advanced
      glycation end-products (sRAGE) is a valuable inflammatory biomarker in
      cardiovascular disease (CVD). Remote ischaemic conditioning may rescue myocardial
      tissue during acute myocardial infarction (AMI). In the present study, we
      evaluate whether sRAGE is a helpful biomarker in patients with AMI receiving
      remote ischaemic conditioning. METHODS: Plasma sRAGE levels were measured in 191
      patients with ST-elevation myocardial infarction (STEMI) treated with primary
      percutaneous intervention (pPCI) of which 97 patients were randomised to receive
      remote ischaemic conditioning. RESULTS: The sRAGE levels were not different when
      compared to the randomised controls. In 122 patients, measurement of myocardial
      salvage index (SI) was obtained. Patients who received remote ischaemic
      conditioning had significantly higher SI compared to the controls (p < 0.03),
      although this effect was not seen in sRAGE concentrations. However, sRAGE levels
      increased with higher New York Heart Association (NYHA) classification after 30
      days of follow-up. CONCLUSIONS: sRAGE levels do not reflect increased SI in AMI
      patients who received remote ischaemic conditioning prior to hospital admission.

PMID- 25975000
TI  - Serum 25-hydroxy vitamin D levels in Bulgarian patients with prostate cancer: a
      pilot study.
AB  - BACKGROUND: The antiproliferative effect of the active form of vitamin D on
      cancer cells and its ability to induce cell differentiation and suppression of
      tumor-induced angiogenesis in the last decade has provoked enormous research for
      the elucidation of its role in the prevention of different types of cancer and in
      slowing down the malignancy progression. The aim of the present pilot study was
      to determine the circulating 25-hydroxy vitamin D (25OHD) levels in Bulgarian
      prostate cancer (PCa) patients and to investigate their relationship with various
      determinants associated with the severity and progression of the disease.
      METHODS: A total of 53 male patients (mean age 67.0 +/- 7.1 years) with clinical
      suspicion for PCa were enrolled in the study. All patients were subjected to
      systemic transrectal ultrasound-guided tru-cut prostate biopsies (10 cores at
      least). Detected tumors were graded using the Gleason grading system. Prostate
      specific antigen (PSA) serum levels were measured immunochemically. The 25OHD
      assay was performed by a validated HPLC-UV method. Other covariates (BMI, age,
      family history of PCa) were collected by interview at the time of
      hospitalization. One-way ANOVA with Kruskal Wallis statistics was used for
      comparison of medians of different parameters. The level of significance was set
      at p < 0.05. RESULTS: Significantly lower 25OHD levels were detected in PCa
      patients compared to those with benign prostate hyperplasia (BPH) (p < 0.05).
      Patients with high grade tumors (Gleason score >= 7) showed significantly lower
      25OHD levels, while those with low grade tumors (Gleason score < 7) revealed
      better 25OHD status (50.49 vs. 63.17 nmol/L, p < 0.05). A moderate negative
      correlation between 25OHD levels and the Gleason score was established (Spearman
      r = -0.46, p < 0.05). Significant seasonal variations in 25OHD levels, both for
      PCa and BPH patients, were detected (p < 0.01). CONCLUSIONS: This preliminary
      study shows an association between 25OHD status and classical markers
      characterizing the severity of PCa. The results might suggest a potential
      beneficial role of vitamin D for PCa patients. Further prospective studies are
      needed to strengthen the interrelationships between 25OHD levels and variables
      related with PCa and to test them for causality.

PMID- 25975001
TI  - Utility of uric acid as a risk marker of extubation success in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The objective of this observational study was to determine whether
      there is an association between extubation success and uric acid in chronic
      obstructive pulmonary disease patients with mechanical ventilation admitted to
      the intensive care units, and identify the risk markers for extubation success in
      COPD patients with mechanical ventilation. METHODS: Consecutive COPD patients
      with intubation were screened at baseline. The study included patients on
      mechanical ventilation (MV) for over 12 hours and who, in the process of weaning,
      were subjected to low-level pressure support. Exclusion criteria were age under
      18 years, ventilation via tracheotomy, and patients failing to cooperate for
      different reasons. The final study population consisted of 106 patients.
      Demographic, clinical, laboratory, and mechanical ventilation parameters were
      carefully recorded. Logistic regression was used for the multivariate analysis of
      independent risk factors. RESULTS: Uric acid on admission, duration of mechanical
      ventilation, pressure support ventilation, and APACHE II score on admission were
      significantly higher in COPD patients with extubation failure than in those with
      extubation success (p < 0.05), but lower tidal volume before weaning was observed
      in COPD patients with extubation failure. Among these patients, multiple logistic
      analyses indicated the independent risk factors for extubation success in the
      COPD subjects included serum uric acid level, APACHE II score on admission, and
      duration of mechanical ventilation. The diagnosis analysis showed that higher
      uric acid level and APACHE II score on admission and longer duration of
      mechanical ventilation had a significant ability to reflect extubation success in
      the COPD patients with respiratory failure. CONCLUSIONS: The novel finding of
      this study is that the extubation failure in COPD patients with respiratory
      failure is strongly related to serum uric acid level, APACHE II score on
      admission, and duration of mechanical ventilation. These results might be helpful
      for selecting the best time to remove the tracheal intubation and improving
      extubation success rate in COPD patients with respiratory failure.

PMID- 25975002
TI  - Role of rhIL-17 in regulating the mitochondrial pathway proteins in peripheral
      blood neutrophils.
AB  - BACKGROUND: IL-17, classified as an inflammatory cytokine, plays a key role in
      the activation of inflammatory processes involving neutrophils. METHODS: Twenty
      healthy voluntary blood donors were controlled in the study. The granulocyte
      suspensions were stimulated with rhIL-17 and fMLP. Expression of Bcl-xl,
      Smac/DIABLO, and Omi/HtrA2 in neutrophil lysates were assessed by Western blot.
      The level of cytochrome c and activity of caspase 9 was also assayed in these
      cells. RESULTS: The results of existing research highlight the importance of rhIL
      17 in reducing the survival of neutrophils via the mitochondria, depending on the
      Bcl-2 protein family. Our research has indicated that rhIL-17 regulates the
      mutual relationships between the proteins of that family. The proapoptotic effect
      observed in neutrophils affected by rhIL-17 is a result of a decreased expression
      of Bcl-xl. Consequently, the expression of apoptogenic proteins, including
      cytochrome c, Smac/DIABLO, and Omi/HtrA2, is elevated. Surprisingly, there have
      been no observations of the cytokine influencing the activity of caspase 9.
      CONCLUSIONS: Results have shown for the first time that IL-17 has a direct effect
      on the decrease of Bcl-xl. In conclusion, the results of the research presented
      in this article confirm the dual action of IL-17, which, on the one hand, leads
      to an array of proinflammatory mechanisms regarding neutrophils and, on the other
      hand, reduces the survival of those cells via an immediate influence on the Bcl-2
      family of proteins and apoptogenic factors.

PMID- 25975003
TI  - Development and validation of a rapid and reliable real-time PCR method for
      CYP3A5 genotyping.
AB  - BACKGROUND: A prominent example for inter-individual differences in drug
      metabolizing enzymes is the cytochrome P450 family. These monooxygenases comprise
      enzymes responsible for metabolism of about 90% of common medications. CYP3A5 and
      CYP3A4 account for 50% of hepatic cytochrome P450 and conversion of about half of
      all their substrates. CYP3A5 is the predominant extra-hepatic CYP enzyme and
      shows varying inter-individual expression attributable to genetic variations in
      the corresponding gene. CYP3A5*2 and *3 are the most common among Caucasian
      populations. Among CYP3A5 substrates are cyclosporine and tacrolimus prescribed
      after organ transplantations. A high incidence of nephrotoxic events after
      administering these drugs is related to low expression of the CYP3A5 enzyme. A
      fast and reliable genotyping method for the CYP3A5 gene would help avoid unwanted
      adverse drug reactions. METHODS: Blood samples from 143 Caucasian subjects were
      genotyped by means of a real-time PCR multiplex assay testing the two CYP3A5
      variations, CYP3A5S*2 and *3. This assay was validated against RFLP-PCR. RESULTS:
      Both mutations examined could be found in the study. No sample was homozygous for
      CYP3A5*2, but 2 out of 143 showed heterozygosity (allele frequency: 0.7%). For
      the CYP3A5*3 variant 17 samples were heterozygous and 115 were homozygous (allele
      frequency 86.4%). The multiplex real-time PCR yields shorter hands-on time and
      reduced cost compared to RFLP-PCR. CONCLUSIONS: Establishment of a multiplex real
      time PCR has been successful as could be proven by correctly identifying the
      desired mutations CYP3A5*2 and CYP3A5*3 against a standard reference method.

PMID- 25975004
TI  - The association between leukocyte telomere length and mitochondrial DNA copy
      number in pregnant women: a pilot study.
AB  - BACKGROUND: Both short telomere length and mitochondrial dysfunction have been
      associated with pregnancy complications, such as preeclampsia and intrauterine
      growth restriction. However, the relationship between these two biomarkers of
      oxidative stress, during pregnancy, is unknown. This study investigated the
      association of leukocyte telomere length with mitochondrial DNA (mtDNA) copy
      number, an indicator of mitochondrial density and possible mitochondrial
      dysfunction, using maternal blood samples collected from women with pregnancies
      uncomplicated by gestational diabetes or hypertensive disorders. METHODS:
      Leukocyte telomere length and mtDNA copy number were determined in 75 pregnant
      women using quantitative real-time quantitative PCR. Bivariate and multivariable
      linear regression procedures were used to evaluate associations of these two
      biomarkers. RESULTS: Leukocyte mtDNA copy number (natural-logarithm) was
      positively associated with telomere length (Pearson correlation coefficient =
      0.30, p-value = 0.009). After adjusting for maternal age and plasma vitamin B12,
      natural-log mtDNA copy number increased by 0.80 (f = 0.80; 95% CI 0.25 - 1.34, p
      value = 0.005) for every 1 unit increase of telomere length. Approximately 11% of
      the variation in natural-long mtDNA copy number was explained by the model
      (adjusted R2 = 0.11). CONCLUSIONS: This cross sectional data suggests an
      association of mtDNA copy number with telomere length, two emergent biological
      markers of potential importance in perinatal health research. The consequences of
      oxidative stress, cellular senescence (as reflected by relatively shorter
      telomere length) and mitochondrial dysfunction, on the course and outcomes of
      pregnancy remain to be elucidated in larger prospective studies that include
      these biological markers.

PMID- 25975005
TI  - Biomarkers for assessing mucosal barrier dysfunction induced by chemotherapy:
      Identifying a rapid and simple biomarker.
AB  - BACKGROUND: Chemotherapy-induced mucosal barrier dysfunction is of clinical
      interest. However, the assessment of mucosal barrier dysfunction still poses
      challenges. In this study, we compared several biomarkers with the dual sugar gut
      permeability test for assessing mucosal barrier dysfunction during chemotherapy.
      METHODS: Forty-two patients with gastric or colorectal cancer underwent
      chemotherapy, including FAM or FOLFOX4 regimens. Patients were asked to grade and
      record their symptoms of gastrointestinal toxicity daily. The urinary lactulose
      mannitol ratio was measured to assess the intestinal permeability. Plasma levels
      of citrulline, diamine oxidase (DAO), D-lactic acid, and endotoxin were also
      measured. Intestinal permeability was observed in the subgroup of patients with
      diarrhea or constipation. RESULTS: The urinary lactulose-mannitol ratio and
      plasma citrulline levels increased on the third and sixth post-chemotherapy days,
      respectively. There were no significant differences in the plasma levels of D
      lactic acid, endotoxin or DAO activity compared to their levels before
      chemotherapy. The urinary lactulose-mannitol ratio in diarrhea patients was
      significantly higher than in constipation patients. CONCLUSIONS: These results
      indicate that the urinary lactulose-mannitol ratio and plasma citrulline level
      are appropriate biomarkers for assessing mucosal barrier dysfunction in patients
      receiving chemotherapy. Mucosal barrier dysfunction in diarrhea patients was
      greater than in constipation patients.

PMID- 25975006
TI  - Assessment of hemostatic changes after initiation of continuous venovenous
      hemodialysis.
AB  - BACKGROUND: Continuous renal replacement therapy (CRRT) is a standard therapy in
      critically ill patients suffering from acute kidney injury (AKI). Extracorporeal
      circulation and exposure to foreign surfaces during CRRT may induce disturbances
      in hemostasis, particularly in platelet function. The present study described the
      hemostatic changes associated with CRRT and aimed to identify the independent
      predictors of premature clotting of the circuit. METHODS: In a prospective cohort
      mono-center study, patients were assessed for eligibility if they were i)
      diagnosed with AKI and ii) assigned to receive CRRT for the first time. Patients
      were included in the study if their platelet count was greater than 100/nL prior
      to inclusion in the study. After initiation of CRRT, aggregometric [Multiplate,
      Roche, Grenzach, Germany: Arachidonic acid (ASPItest)-, ADP (ADPtest)- and
      Thrombin (TRAPtest)-induced platelet aggregation] and viscoelastic (ROTEM; TEM
      International, Munich, Germany) analyses were performed immediately before
      (Baseline, T1) and 6 hours (T2), 12 hours (T3), 24 hours (T4), and 48 hours (T5)
      after initiation of CRRT. Conventional laboratory coagulation analyses were
      routinely performed twice a day. Arachidonic acid- and ADP-induced platelet
      aggregations were defined as primary endpoints. RESULTS: A total of 127 patients
      were screened for eligibility, and 50 patients were enrolled in this study.
      Aggregometric analyses showed that arachidonic acid-induced platelet aggregation
      was significantly reduced at T2 [532 (210/1105) median (25th/75th percentile)
      AU*min] compared to the Baseline at T1 [780 (297/1156), p = 0.007] and remained
      unchanged from T2 onward. Platelet aggregation in the ADPtest and TRAPtest
      remained unchanged during the study period. Viscoelastic and conventional
      coagulation analyses indicated a progredient increase of clot firmness. In total,
      76 filter sets (an average of 1.5 per patient) were used, and 26 filter sets
      occluded prematurely after an average treatment time of 17 +/- 12 hours. No
      predictors for premature clotting of the circuit were identified. CONCLUSIONS:
      The results of the present study indicate that CRRT may lead to impaired primary
      hemostasis as shown by a decrease in ex vivo arachidonic acid-induced platelet
      aggregation. Moreover, viscoelastic measure indicate a fibrinogen-associated
      trend of increasing clot firmness during the study period. Further studies are
      needed to analyze whether these findings are of hemostatic relevance.

PMID- 25975007
TI  - Dietary fatty acids affect lipid metabolism and estrogen receptor expression in N
      methyl-N-nitrosourea-induced rat mammary cancer model.
AB  - BACKGROUND: We hypothesized that dietary polyunsaturated fatty acids (PUFA) could
      affect the expression of serum fatty acid binding protein 5 (FABP5) and CD36
      levels and also fatty acid synthase (FAS), and estrogen receptor (ER) expressions
      in breast cancer cells. METHODS: A rat mammary cancer model was induced by
      injection i.p., with 50 mg MNU/kg body weight. Low (13.8% energy) or high-fat
      (42.5% energy) diets composed mainly of n-6 or n-3 PUFAs originating either from
      linoleic acid or linolenic acid, respectively, were given for eight weeks. After
      sacrifice at week 8, serum FABP5 level was examined and immunostainings of CD36,
      FAS, and ER of breast cancer tissue were observed. RESULTS: By week 8, there was
      no statistical difference of tumor formation rate between each group. The level
      of serum FABP5 in the high n-3 group was significantly lower than the low n-6 and
      high n-6 groups. Immunohistochemistry results showed that there was a significant
      difference of CD36 expression between the low n-3 group and high n-6 group (p <
      0.05). Although the high n-3 group had the most inhibition on FAS and ER
      expression, there was no statistical difference between each group. CONCLUSIONS:
      Our study showed that different dietary PUFAs may affect lipid metabolism in
      breast cancer tissues by altering the expression of FABP5, CD-36, FAS, and ER,
      which may change treatment response and even prognosis of breast cancer.

PMID- 25975008
TI  - Effect of n-3 and n-6 polyunsaturated fatty acids on lipid metabolic genes and
      estrogen receptor expression in MCF-7 breast cancer cells.
AB  - BACKGROUND: To investigate the effect of different ratios of n-6/n-3
      polyunsaturated fatty acids (PUFAs) on the expression of lipid metabolic genes
      and estrogen receptor (ER). METHODS: This study took place in the Department of
      Surgery, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou,
      China, between January 2012 and October 2013. MCF-7 breast cancer cells were
      cultured for 48 hours with different ratios of PUFAs. Cell proliferation
      capability was detected by MTT method. Lipid metabolic genes and estrogen
      receptor (ER) were detected by western blot. RESULTS: Compared with the control
      group, the single n-6 PUFA group had no effect on sterol-regulatory-element
      bindingprotein (SREBP) and fatty acid synthase (FAS) expression, while other
      groups all inhibited their expressions. Single n-6 group and 2:1 n-6/n-3 group
      down-regulated the expression of peroxisome proliferator-activated receptor
      (PPARgamma), while in the other groups it was up-regulated. Single n-3 and n-6
      groups had no effect on ER expression, while the others all suppressed the ER
      expression. CONCLUSIONS: Different ratios of n-6/n-3 polyunsaturated fatty acids
      may suppress the ER expression of MCF-7 cells and the effect may be related to
      its effect on the expression of lipid metabolic genes.

PMID- 25975009
TI  - The effect of thalassemia on erythrocyte reference intervals in a representative
      Han Chinese adult population.
AB  - BACKGROUND: The data from apparently healthy individuals with thalassemia has
      been demonstrated to have an effect on the reference intervals for the
      erythrocyte indices in areas with a high incidence of thalassemia. METHODS: Six
      clinical centers screened apparently healthy individuals using a questionnaire
      and a physical examination. Then, the qualified reference individuals were
      selected by hematological indices and a genotypic thalassemia diagnosis.
      Statistical comparisons were conducted for the erythrocyte reference intervals in
      the Chinese population with and without thalassemia. The constituent ratios and
      the mean (SD) of erythrocyte indices according to the thalassemia genotype were
      calculated. The relationship between the MCV values and the thalassemia genotype
      was also estimated. RESULTS: 4,636 reference individuals were included using
      hematological indices and genotypic thalassemia screening. The results of the
      erythrocyte reference intervals for individuals in Guangzhou with thalassemia
      demonstrated that the RBC, MCV, and MCH values significantly differed by gender
      compared with other regions (p < 0.01). In contrast, for individuals without
      thalassemia, the results tended to be similar and clinically acceptable. In
      addition, the results of the erythrocyte indices revealed significant differences
      among alpha-thalassemia patients, beta-thalassemia patients, and the control
      group. CONCLUSIONS: Apparently healthy individuals with thalassemia in the high
      prevalence zone of thalassemia could not be excluded by the questionnaire,
      physical examination or laboratory indices (Fe < 6 MUmol/L, Hb < 90 g/L). The
      screening of genotypic thalassemia based on the MCV or MCH values to exclude
      unqualified individuals is the most effective way to obtain accurate and reliable
      reference intervals for the erythrocyte indices.

PMID- 25975010
TI  - Cryopreservation of whole ovine ovaries with pedicles as a model for human:
      parameters of perfusion with simultaneous saturations by cryoprotectants.
AB  - BACKGROUND: The aim of this research was to study the effectiveness of perfusion
      of intact ovine ovaries with different rates of perfusion and time-period elapsed
      between extraction of these ovaries and the beginning of perfusion. METHODS:
      Ovaries were perfused through the arteria ovarica (ovarian arteries) with culture
      medium supplemented with 5% bovine calf serum, 6% dimethyl sulfoxide, 6% ethylene
      glycol, 0.15M sucrose, Indian ink, and 100 IU/mL heparin at room temperature (22
      degrees C). In the first cycle of experiments, ovaries (n = 96) were perfused for
      60 minutes just after extraction of ovaries at the following rates of perfusion
      (mL/hour): 150, 100, 75, 50, 25, 12.5, and 6.3. In the second cycle of
      experiments, ovaries (n = 26) were perfused at a rate of 25 mL/hour for 60
      minutes after extraction of ovaries and their storage at room temperature for 2,
      3, 4, and 5 hours, for groups 1, 2, 3, and, 4, respectively. Successful perfusion
      of blood vessels was detected visible by a blue coloration of the ovarian
      tissues. RESULTS: The first cycle of experiments showed that the optimal
      perfusion rates were 50 mL/hour and 25 mL/hour. In the second cycle of
      experiments, good perfusion of ovaries was established at a perfusion rate of 25
      mL/hour for the ovaries of groups when 2 and 3 hours had elapsed after
      extraction. CONCLUSIONS: Effective perfusion of ovine intact ovaries with
      vascular pedicle was established using freezing medium at room temperature at the
      rate of perfusion of 25 mL/hour or 50 mL/hour. The ovaries must be perfused not
      later than 3 hours after the death of animals.

PMID- 25975011
TI  - Butrylcholinesterase activity in chronic liver disease patients and correlation
      with Child-Pugh classification and MELD scoring system.
AB  - BACKGROUND: After 40 years since establishment of Child-Pugh staging, 14 years
      since establishment of MELD scoring system, and 25 years since establishment of
      King's College Criteria, there is still a search for more accurate systems for
      determination of prognosis in patients with acute liver failure--cirrhosis and
      prioritization for receipt of a liver transplant--prediction of post transplant
      mortality. Butrylcholinesterase is an enzyme which is synthesized in the liver.
      The aim of the study was to evaluate the clinical utility of butrylcholinesterase
      as a discriminatory and prognostic factor in chronic liver disease patients.
      METHODS: Intergroup diversity for butrylcholinesterase activity was investigated
      in sixty cirrhotic, 20 chronic hepatitis patients, and 20 healthy subjects.
      Correlations between butrylcholinesterase activity and Child-Pugh classification
      and MELD scoring systems were examined. RESULTS: In addition to the statistically
      significant decrease in butrylcholinesterase activity among Child-Pugh A/B/C
      stages, the decrease in butrylcholinesterase activity was also statistically
      significant in control vs. Child-Pugh stage A and chronic hepatitis vs. Child
      Pugh stage A groups. A statistically significant correlation was determined
      between butrylcholinesterase activity and Child Pugh/MELD scores. CONCLUSIONS:
      Serum butrylcholinesterase activity might be helpful for discrimination of
      chronic hepatitis from cirrhosis after determination of reliable cut-off levels
      and dependent on the reductions of serum levels in acute liver failure and
      cirrhosis. It might be a useful tool for prioritization of liver transplantation.

PMID- 25975012
TI  - Hemoperitoneum from corpus luteum rupture in patients with aplastic anemia.
AB  - BACKGROUND: Aplastic anemia is a rare hematopoietic stem-cell disorder that
      results in pancytopenia and hypocellular bone marrow. Women with aplastic anemia
      usually are at increased risk of corpus luteum rupture due to thrombocytopenia
      and infection. METHODS: Here we report two cases had hemoperitoneum from corpus
      luteum rupture in patients with aplastic anemia in our center. RESULTS: Case 1
      involved two episodes of hemoperitoneum resulting from rupture of the corpus
      luteum in a 23-year-old unmarried female with severe aplastic anemia. This
      patient was managed conservatively with platelet and packed red cell transfusion.
      Case 2 involved two episodes of hemoperitoneum resulting from rupture of the
      corpus luteum in a 33-year-old married patient with aplastic anemia. Emergency
      laparoscopy revealed massive hemoperitoneum. Bilateral salpingo-oophorectomy were
      performed successively with platelet and packed red cell transfusion.
      CONCLUSIONS: Hemoperitoneum resulting from a ruptured corpus luteum is a life
      threatening condition in patients with aplastic anemia. Prompt and appropriate
      evaluation of corpus luteum rupture and emergent therapy are needed.

PMID- 25975013
TI  - Effect of salt supplementation on the rate of inadequate sweat collection for
      infants less than 3 months of age referred for the sweat test.
AB  - BACKGROUND: Sweat testing in young infants (<= 3 months) with a positive newborn
      screen for Cystic Fibrosis (CF) can yield higher rates of inadequate sweat
      collection. The role of salt supplements in improving sweat collection has not
      been studied before. METHODS: All young infants referred to our CF center for
      sweat testing were randomized to either receive salt supplements {1/8th teaspoon
      salt (750 mg)} mixed in formula feeds 1 day prior to sweat testing (study group)
      or no salt supplement (controls). RESULTS: Of the 151 young infants that
      underwent sweat testing over 18 months, 75 received salt supplements, while 76
      did not. A total of 9 (11.8%) infants in the salt supplement group had inadequate
      sweat collection, as compared to 4 (5.2%) infants in the control group (p = 0.16,
      Fisher's Exact Test). CONCLUSIONS: Oral salt supplementation for young infants
      prior to sweat testing does not help to reduce the rates of inadequate sweat
      collection.

PMID- 25975014
TI  - Comparison of high-resolution melting analysis, Sanger sequencing and ARMS for
      KRAS mutation detection in metastatic colorectal cancer.
AB  - BACKGROUND: Treatment of metastatic colon carcinoma with the anti-epidermal
      growth factor receptor antibody cetuximab/panitumumab is reported to be
      ineffective in KRAS-mutant tumors; therefore, it is necessary to perform KRAS
      mutation analysis before cetuximab or panitumumab treatment is initiated.
      METHODS: This study was designed to compare and evaluate the efficacy of three
      different methodologies--high resolution melting (HRM), Sanger sequencing, and
      Amplification Refractory Mutation System (ARMS)--for KRAS mutation detection in a
      clinical setting. RESULTS: In total, 55 samples from patients with metastatic
      colorectal cancer were analyzed. Compared to Sanger sequencing, good consistency
      was found between the results of the ARMS (Kappa = 0.839) and HRM (Kappa =
      0.839). The sensitivities of the methods were compared after a consensus was
      reached: if two of the three methodologies showed a similar result, it was
      considered as the consensus result. The frequency of KRAS mutations in our
      population was 34.5%, and discordant findings were observed in five samples. No
      significant difference in sensitivity was found among the three methodologies.
      CONCLUSIONS: From the results, we can conclude that after careful in-laboratory
      validation, HRM is a good alternative to the ARMS and Sanger sequencing for KRAS
      mutation testing.

PMID- 25975015
TI  - To screen for CALR mutations in patients with splanchnic vein thrombosis?

PMID- 25975016
TI  - Possible influence of some foods on the metabolism of ibrutinib.
AB  - Since 2014, Ibrutinib has been available as a new drug for the treatment of
      leukemic diseases. Ibrutinib (Imbruvica) is metabolized in the liver mainly by
      the isoenzyme CYP3A4 and to a minor extent by CYP2D6. Simultaneous application of
      Imbruvica and consumption of foods containing secondary metabolites strongly
      inhibiting the CYP3A4 isoform, could significantly influence the toxicity of this
      drug. This article references the respective foods.

PMID- 25975017
TI  - [Alteration of related transporters and its application significance in common
      intestinal disease, liver disease, renal disease and diabetes].
AB  - Drug transporters are functional membrane proteins located in various tissues,
      which play vital roles in absorption, distribution and excretion of drugs,
      especially those located in intestine, liver and kidney. The expression and
      function of transporters will alter in diseases state, which affects the
      therapeutic effects of drugs by altering their pharmacokinetics. In this review,
      we focus on the alterations in related transporters and the effect on the drug
      therapy in common intestinal diseases, liver diseases, kidney diseases and
      diabetes mellitus.

PMID- 25975018
TI  - [Roles of the cross talk between MAP kinases and Keap1-Nrf2-ARE signaling
      pathways in chronic obstructive pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD), a common preventable and treatable
      disease, is characterized by airflow limitation that is usually progressive and
      associated with an enhanced chronic inflammatory response in the airways. Its
      main pathological manifestations include airway inflammation, mucus
      hypersecretion, oxidative stress and apoptotic epithelial cells. Recent research
      suggests that MAP kinases and Keap1-Nrf2-ARE signaling pathway are involved in
      the pathological process of inflammation and oxidative stress. This review
      explores the potential role of the cross talk of these signaling pathways in
      airway inflammation, mucus hypersecretion, oxidative stress and apoptotic
      epithelial cells. To clarify the roles of cross talk between MAP kinases and
      Keap1-Nrf2-ARE signaling pathway, we also focus on the drugs related to that in
      the treatment of COPD, and it provides ideas for more drug research in the
      treatment of COPD.

PMID- 25975019
TI  - [The application of enzyme-sensitive activatable cell-penetrating peptides to
      targeted delivery system].
AB  - Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent
      mode to promote cellular uptake. Although the non-specificity of CPP-mediated
      internalization allows this approach applicable to a wide range of tumor types
      potentially, their universality is a significant obstacle to their clinical
      utility for targeted delivery of cancer therapeutics and imaging agents.
      Accordingly, many reports have focused on selective switching of systemically
      delivered inert CPPs into their active form in lesions (tumor). In this review,
      our attention is mainly confined to such an enzyme-sensitive domain incorporated
      delivery system with activatable CPPs (ACPPs), which have displayed the exciting
      strength in balancing the CPPs' pros and cons, and potential in the treatment and
      diagnosis of some diseases.

PMID- 25975020
TI  - [The basic strategies and research advances in the studies on
      glycosyltransferases involved in ginsenoside biosynthesis].
AB  - Traditional herbal medicines, Panax ginseng, Panax quinquefolium and Panax
      notoginseng, attract our attention for their extensive and powerful
      pharmacological activities. Ginsenosides are the main active constituents of
      these medicinal herbs. The related glycosyltransferases involved in ginsenoside
      biosynthesis are the key enzymes which catalyze the last important step.
      Modification of ginsenoside aglycones by glycosyltransferases produces the
      complexity and diversity of ginsenosides, which have more extensive
      pharmacological activity. At present, ginsenoside aglycones and compound K have
      been obtained by synthetic biology. As the last step of ginsenoside biosynthesis,
      glycosylation of ginsenoside aglycones has been studied intensively in recent
      years. This review summarizes the basic strategies and research advances in
      studies on glycosyltransferases involved in ginsenoside biosynthesis, which is
      expected to lay the theoretical foundation for the in-depth research of
      biosynthetic pathway of ginsenosides and their production by synthetic biology.

PMID- 25975021
TI  - [Antiosteoporotic effects of naringenin on ovariectomy-induced osteoporosis in
      rat].
AB  - To investigate the effect of naringenin on ovariectomy-induced postmenopausal
      osteoporosis comprehensively and systemically, thirty-two virgin Sprague-Dawley
      rats about 3-month-old were used and randomly divided into 4 groups: sham control
      group (Sham), OVX control group (OVX), naringenin treatment group and 17beta
      estradiol (E2) treatment group. After 12 weeks treatment with different drugs, 24
      h urine were collected, organs were weighed and the organ indies were computed.
      Uterine pathological changes were observed by making paraffin section.
      Biochemical parameters and bone turnover markers: serum osteocalcin (BGP) and
      urine deoxypyridinoline (DPD) were analyzed with automatic biochemical analyzer
      or ELISA assay. Bone mineral density (BMD) and bone mineral content (BMC) were
      analyzed by DEXA, bone biomechanical properties was measured by three point
      bending test and the trabecular bone microarchitecture was evaluated by Micro CT.
      From the results, we can see that: the gaining of weight and the increasing of
      bone turnover markers such as serum BGP and urinary DPD could be inhibited by
      naringenin. The treatment could also enhance the bone strength and prevent the
      deterioration of trabecular microarchitecture, increase the bone volume,
      trabecular number and thickness, and decrease the trabecular space. The effects
      mentioned above were not accompanied with stimulating effects on uterus. Long
      term using of naringenin had no obvious influence on other organs and the liver
      and kidney functions. The study suggests that naringenin had obvious
      antiosteoporotic effect on ovariectomized rats and it had the potential value for
      the treatment of postmenopausal osteoporosis.

PMID- 25975022
TI  - [Protective effect of ligustilide against glutamate-induced apoptosis in PC12
      cells].
AB  - To investigate the neuroprotective of ligustilide (LIG) against glutamate-induced
      apoptosis of PC12 cells, cell viability were examined by MTT assay. Flow
      cytometry was applied to assay cell apoptosis rate. Intracellular calcium
      concentration was measured by using fluorescent dye Fluo-3/AM. Cytochrome C (Cyt
      C), Caspase-3, Bax and Bcl-2 protein expression were assayed by western blot. The
      results showed that glutamate is cytotoxic with an inhibitory concentration 50
      (ID50) of 15 mmol . L(-1). Pretreatment with LIG (1, 5, 15 MUmol . L(-1))
      significantly improved cell viability. The apoptosis rate in glutamate-induced
      PC12 cells was 13.39%, and decreased in the presence of LIG (1, 5, 15 MUmol . L(
      1)) by 9.06%, 6.48%, 3.82%, separately. Extracellular accumulation of Ca2+
      induced by glutamate were significantly reduced by LIG. The results of western
      blot manifested that pretreatment LIG could decrease the release of Cyt C from
      mitochondria, down-regulate Caspase-3 protein expression and up-regulate Bcl
      2/Bax ratio, thereby protects PC12 cells from apoptosis. In summary, LIG had
      protective effect on glutamate-induced apoptosis in PC12 cells through
      attenuating the increase in intracellular Ca2+ concentration, and inhibiting the
      release of Cyt C from mitochondria to cytoplasm.

PMID- 25975023
TI  - [Establishment and application of a high-throughput drug screening model based on
      COL1A1 promoter for anti-liver fibrosis].
AB  - For screening the potential drugs as anti-liver fibrosis candidates, we
      established a high- throughput drug screening cell model based on COL1A1
      promoter. The activity of COL1A1 promoter and luciferase reporter gene can be
      elevated by TGF-beta1, and inhibited by candidate drugs. We constructed a
      recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.17, the
      activity of COL1A1 promoter was reflected by fluorescence intensity. COL1A1
      promoter activity was detected by Dual-Luciferase Reporter Assay System, it came
      that the relative luciferase activity of COL1A1 promoter was 15.98 times higher
      than that of control group induced by TGF-beta1, showing the recombined plasmid
      could be used in cell model. The recombined plasmid was transfected into human
      hepatic stellate cells LX2, detected the effect of potential drugs, and obtained
      a stable expression system through stable transfection and monoclonal cell
      culture. A sample which could reduce COL1A1 promoter activity signally by our
      cell model, decreased collagen I mRNA and protein expression detected by real
      time RT-PCR and Western blotting. It indicates this novel cell model can be used
      in high-throughput drug screening of potential anti-liver fibrosis drugs.

PMID- 25975024
TI  - [Effects of chrysophanol on expression of SREBPs and lipid metabolism in Huh-7
      cells].
AB  - Rhubarb is a traditional Chinese medicines which possess laxative, lipid
      lowering, and weight-loss activities, but the active compounds of lipid-lowering
      and underlying molecular mechanisms are not yet clear. This study aims to explore
      the effects of chrysophanol on the mRNA expressions of sterol regulatory element
      binding proteins (SREBPs) and lipid metabolism in human liver carcinoma Huh-7
      cells, which is one of the active compounds obtained from Rhubarb. A reporter
      gene assay was used to test the transcription of SREBP. The intracellular
      triglyceride and total cholesterol contents were measured by using commercially
      available test kits. The SREBPs target genes expressions were measured by
      Quantitative Real-Time PCR. Cell viability was evaluated by Cell Counting Kit-8.
      As the results shown, chrysophanol (40 MUmol . L(-1), 16 h) could notably
      inhibited human SRE promoter activity in a dose-dependent manner and decrease
      intracellular cholesterol and triglyceride levels. Furthermore, the mRNA
      expressions of SREBPs target genes were significantly downregulated by
      chrysophanol treatment. However there are no significant differences on cell
      viability when compared with the control group. These results suggested that
      chrysophanol might improve lipid metabolism through suppressing the mRNA
      expressions of SREBPs target genes to attenuate intracellular lipid accumulation.

PMID- 25975025
TI  - [Associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese
      renal transplant recipients].
AB  - The study aims to investigate the associations of SUMO4 polymorphisms with
      tacrolimus concentrations in Chinese renal transplant recipients. Blood samples
      and clinical data were collected from 132 renal transplant recipients with
      tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP, and SUMO4
      (rs237024, rs237025) genotypes were detected by Sequenom(r) MassARRAY system.
      SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium (D'
      = 1). The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A
      (GA-GA +AA-AA) carriers was considerably higher than that in GG-GG carriers (P <
      0.05). After stratification by CYP3A5*3 genotypes, SUMO4 rs237024A-rs237025A
      carriers (GA-GA+AA-AA) had a higher dose-adjusted tacrolimus concentration than
      that in GG carriers in CYP3A5 expresser (P < 0.05). The results illustrated that
      SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus
      concentrations, and the test of these genotypes may be useful for individualized
      medicine of tacrolimus.

PMID- 25975026
TI  - [Design, synthesis of novel N, N'-bis-(halogenophenyl)-4- methoxybenzene-1, 3
      disulfonamides and evaluation of their anti-platelet aggregation activity].
AB  - Combining the structural features of picotamide and linotroban, a series of N,N'
      bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and
      synthesized on the basic principles of drug design. The structures of target
      compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet
      aggregation activity was evaluated by Born turbidimetric method with adenosine
      diphosphate (ADP) as the platelet aggregation inducers. The assay results showed
      that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to
      have superior anti-platelet aggregation activities than the positive drug
      picotamide. The preliminary structure-activity relationship (SAR) has been
      explored.

PMID- 25975027
TI  - [Design, synthesis and biological evaluation of novel [1,3] dioxolo [4,5
      f]isoindolone derivatives].
AB  - A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized
      and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their
      effects on memory impairment of mice induced by scopolamine were investigated
      with step-through test. The results suggested that most of the target compounds
      exhibited potential inhibition on AChE with IC50 values at micromolar range.
      Compounds I1 (IC50 value of 0.086 MUmol . L(-1)) and I2 (IC50 value of 0.080
      MUmol . L(-1)) showed the strongest AChE inhibitory activity, which are
      equipotent to donepezil (IC50 value of 0.094 MUmol . L(-1)). Moreover, compounds
      I1-I4 could improve the memory impairment induced by scopolamine in mice.

PMID- 25975028
TI  - A new selaginellin derivative from Selaginella pulvinata.
AB  - Abstract: A new selaginellin derivative named as selaginellin S (1) was isolated
      from the whole plants of Selaginella pulvinata (Hook. et Grev.) Maxim.
      (Selaginellaceae), together with a known one (selaginellin M, 2). Compounds 1 and
      2 were separated and purified by silica gel and Sephadex LH-20 column
      chromatography. Their structures were determined on the basis of extensive
      spectroscopic analysis including IR, MS, 1D and 2D NMR experiments, as well as
      ECD calculations. Compound 1 is a key intermidiant in the biosynthesis pathway of
      selaginellins. Compound 2 is first reported in this plant.

PMID- 25975029
TI  - A novel citrinin derivative from the marine-source fungus Penicillium citrinum.
AB  - A novel citrinin derivative, penicitrinol L (1), along with two known analogues,
      penidicitrinin B (2) and pennicitrinone A (3) were isolated from the marine
      source fungus Penicillium citrinum. The structure of the new compound was
      elucidated by spectroscopic methods including one and two-dimensional NMR as well
      as high-resolution mass spectrometric analysis. Furthermore, compound 1 showed
      modest cytotoxic activity against HL-60 cell line and compound 3 showed weak
      cytotoxic activity against A375 cell line.

PMID- 25975030
TI  - [Chemical constituents of the roots of Macleaya microcarpa and activation
      efficacy of benzophenanthridine alkaloids for the transcription of xbp1 gene].
AB  - Ongoing study on the chemical constituents of the roots of Macleaya microcarpa
      led to the isolation of eight compounds of derivatives of triterpenes and organic
      acids in addition to some previously identified benzophenanthridines. The eight
      compounds were identified by spectroscopic methods as well as comparison with
      literature values as 1-oxo-2, 22 (30)-hopandien-29-oic acid (1), 3-oxo-12-oleanen
      30-oic acid (2), 3alpha-hydroxy-12-oleanen-30-oic acid (3), 3beta-hydroxy-12
      oleanen-30-oic acid (4), ferulic acid (5), ferulic acid 4-O-beta-D-glucoside (6),
      3-O-feruloylquinic acid (7), and methyl 3-O-feruloylquinate (8). Of which, 1 is a
      new triterpenoid of hopanes and 2-8 are isolated from M microcarpa for the first
      time. In order to discover natural active compounds as potential agents of anti
      ulcerative colitis (UC), an in vitro drug high-throughput screening model
      targeted x-box-binding protein 1 (xbp1) was employed to evaluate the activity of
      the major chemical constituents of M microcarpa. The result confirmed that two
      dihydrobenzophenanthridines, dihydrosanguinarine (9) and dihydrochelerythrine
      (10), showed a certain activity on activating the transcription of xbpl, a
      transcription factor (TF) associated with the occurrence, development, and
      potential treatment of UC, with their relative activating ratios being 1.76 and
      1.77 times, respectively, as compared with control group.

PMID- 25975031
TI  - [Comparison of chemical composition between raw and vinegar-baked Paeoniae Radix
      Alba using NMR based metabolomic approach].
AB  - To compare the chemical change of Paeoniae Radix Alba (PRA) after vinegar-baking
      processing, as well as the effect of vinegar types exerted on the processing, 1H
      NMR-based metabolomic approach combined with multivariate statistical analysis
      was used to investigate the different metabolites between the raw and two vinegar
      baked PRA. More than thirty metabolites were identified in the 1H NMR spectrum of
      PRA, and the multivariate statistical analysis showed that raw and two vinegar
      baked PRA could be separated obviously. After vinegar-baking, the contents of
      isoleucine, lactate, alanine, arginine, albiflorin, and 5-hydroxymethyl furfural
      (5-HMF) elevated, while those of sucrose, paeoniflorin and its analogues
      (calculated by benzoate) decreased. The chemical compositions of two vinegar
      baked PRA were also different. Shanxi vinegar- baked PRA showed higher levels of
      leucine, isoleucine, valine, and albiflorin, while rice vinegar-baked PRA
      contained more sucrose and paeoniflorin's analogues (calculated by benzoate). And
      the chemical changes in Shanxi vinegar-baked PRA were greater than those of rice
      vinegar-baked PRA. The results revealed the chemical differences between raw and
      vinegar-baked PRA, as well as the influence of vinegar type on processing, in a
      holistic manner, the results obtained suggested that the correlations between the
      chemical change and the drug action after processing, as well as the vinegar type
      used in processing, should be further studied.

PMID- 25975032
TI  - [Pharmacokinetic comparison of two ozagrel polymorph forms in SD rats].
AB  - To enhance the quality and efficiency of ozagrel by investigating the differences
      between the ozagrel polymorphs in bioavailability. Solid ozagrel in different
      polymorph forms were orally administered to SD rats. An HPLC method was
      established to determinate plasma level of ozagrel. The bioavailabilities of two
      polymorph forms were calculated and compared. The pharmacokinetic parameters of
      ozagrel, were as follows: Cmax was 32.72 +/- 17.04 and 34.01 +/- 19.13 mg . L(
      1), respectively; AUC0-t was 61.14 +/- 14.76 and 85.56 +/- 18.08 mg . L(-1) . h,
      respectively; t1/2 was 1.53 +/- 0.51 and 4.73 +/- 3.00 h, respectively. There was
      no significant difference in pharmacokinetic parameters between form I and II
      polymorphs of ozagrel while the t1/2 of form II is longer, which indicates that
      the use of form II polymorph as pharmaceutical product may prolong the effective
      action time in clinics. This would help the polymorph quality control in drug
      production.

PMID- 25975033
TI  - [Solidification of volatile oil with graphene oxide].
AB  - To evaluate the properties of solidifying volatile oil with graphene oxide, clove
      oil and zedoary turmeric oil were solidified by graphene oxide. The amount of
      graphene oxide was optimized with the eugenol yield and curcumol yield as
      criteria. Curing powder was characterized by differential scanning calorimetry
      (DSC) and scanning electron microscopy (SEM). The effects of graphene oxide on
      dissolution in vitro and thermal stability of active components were studied. The
      optimum solidification ratio of graphene oxide to volatile oil was 1:1.
      Dissolution rate of active components had rare influence while their thermal
      stability improved after volatile oil was solidified. Solidifying herbal volatile
      oil with graphene oxide deserves further study.

PMID- 25975034
TI  - [Cloning and functional characterization of pathogenesis-related PR10-1 gene in
      Panax notoginseng].
AB  - With homology cloning approaches coupling with RACE (rapid-amplification of cDNA
      ends) techniques, the full-length coding sequence of pathogenesis-related protein
      PR10-1 with differential expression was cloned from the total RNA of the root of
      Panax notoginseng, and its function was explored furtherly. As a result, the
      longest 465 bp ORF (named as PnPR10-1 with the Accession No. KJ741402 in GenBank)
      was detected from the cloned sequence with full-length of cDNA of 863 bp. The
      corresponding peptide encoded consisted of 155 amino acids, contained some
      domains such as Bet-v-I, and showed high similarity with that from Panax ginseng
      by analysis of phylogenetic trees created from the alignments. Real-time
      quantitative PCR showed that the expression of PnPR10-1 gene was constitutive in
      different tissues of 1-3 year old plant, suggesting that it might be involved in
      growth, development, and secondary metabolism; yet it was up-regulated
      significantly with the infection of Fusarium oxysporum in root, suggesting that
      it might be involved in defense against many diseases including root rot in P.
      notoginseng.

PMID- 25975035
TI  - [Cloning and expression analysis of the expansin gene RgEXPA10 in Rehmannia
      glutinosa].
AB  - Using cDNA from Rehmannia glutinosa leaf as template, a 972 bp fragment of
      expansin gene which containing a 762 bp ORF that encoded 253 amino acids, was
      cloned, named RgEXPA10, which GenBank accession number for this gene is KF011918.
      A 1 207 bp genomic sequence of RgEXPA10 was amplified by PCR with leaf DNA as
      template, sequencing analysis revealed that three exons and two introns in
      RgEXPA10 genomic sequence, and which GenBank accession number is KF011919.
      Molecular and bioinformatic analyses indicated that RgEXPA10 protein have DPBB_1
      and Pollen_allerg_1 domain, also including a 26 aa nuclear localization signal
      and a 19 aa transmembrane region. Phylogenetic analysis revealed that RgEXPA10
      showed the highest homology with AtEXPA8 among the 26 alpha-expansins in
      Arabidopsis thaliana. However, the RgEXPA10 indicated the highest homology with
      the expansin from Solanum lycopersicum among 22 plant species. Expression
      patterns using qRT-PCR analysis showed that RgEXPA10 mainly expressed in unfolded
      leaf, followed by the tuberous root at stage of expanding period, and rarely
      expressed in senescing leaf. And RgEXPA10 showed higher expression level in
      tuberous root at 60 and 90 days after emergence. The transcription level of
      RgEXPA10 significantly reduced under all the three stresses including continuous
      cropping conditions, salinity and waterlogging. This study will lay foundations
      for molecular function in development and regulation of different stresses for R.
      glutinosa.

PMID- 25975036
TI  - My hat's off to nurses!

PMID- 25975037
TI  - Conversation starter.

PMID- 25975038
TI  - Intention-to-treat analysis in RCTs.

PMID- 25975039
TI  - From war to peace: listening in. 1925.

PMID- 25975040
TI  - In rural Alberta. 1935.

PMID- 25975041
TI  - Helping seniors find new horizons. Do you have an idea for a project that engages
      seniors and strengthens your community?

PMID- 25975042
TI  - Harnessing the web to build research capacity. Innovative network brings B.C.
      nurses and other members together virtually.

PMID- 25975043
TI  - On being present and aware.

PMID- 25975044
TI  - Potassium dehydroandrographolide succinate injection for treat- ment of infantile
      pneumonia: a systematic review and Meta-analysis.
AB  - OBJECTIVE: To evaluate systematically the clinical efficacy and safety of
      potassium dehydroandrographolide succinate injection (PDS) in treatment of
      infantile pneumonia. METHODS: Randomized controlled trials (RCTs) of infantile
      pneumonia treated by PDS were searched in China National Knowledge Infrastructure
      Database, China Science and Technology Journal Database, Wanfang Database,
      Chinese Biomedical Literature Database, PubMed, and Cochrane Library, from
      January 1979 to July 2013. Two reviewers independently retrieved the RCTs and
      extracted the information. The quality of included studies was assessed by the
      Cochrane risk of bias, and a Meta-analysis was conducted with Review Manager 5.2
      software. RESULTS: A total of 9 studies with 1056 participants were included. The
      quality of the studies was generally no high, only one study mentioned the random
      method. The Meta-analysis indicated that PDS was significantly superior to the
      conventional therapy in the total effective rate [relative risk (RR) = 1.21, 95%
      CI (1.14, 1.27), P < 0.000 01], the time of temperature recovery [mean difference
      (MD) = -1.43, 95% CI (-1.75, -1.11), P < 0.000 01], rale disappeared and cough
      relieving [MD = -1.44, 95% CI (-1.93, -0.90), P < 0.000 01]. Six adverse drug
      reactions from five studies mainly represented rash and diarrhea, and no serious
      ADRs were reported. CONCLUSION: Based on this systematic review, PDS was proved
      effective and relatively safe in treatment of infantile pneumonia. However the
      articles enrolled in the study were not high in quality, studies with higher
      quality should be conducted for assessment of efficacy and safety of PDS in
      treatment of infantile pneumonia.

PMID- 25975045
TI  - Effect of transcutaneous electrical nerve stimulation at acupoints on patients
      with type 2 diabetes mellitus: a randomized controlled trial.
AB  - OBJECTIVE: To examine whether transcutaneous electric nerve stimulation at
      acupoints (Acu-TENS) improved the biochemical and physical indices of patients
      with type 2 diabetes mellitus (T2DM). METHODS: Ninety subjects with T2DM were
      divided randomly into a control group (n = 30), aerobic exercise group (n = 30),
      or Acu-TENS group (n = 30). In addition to conventional diabetes drug treatment,
      patients in the Acu-TENS group received acupoint stimulation, the aerobic
      exercise group engaged in walking exercises, and the control group was given sham
      electrical stimulation. All groups were treated for 30 min for each session and
      five times a week for 2 months. The indices of glycosylated hemoglobin, 2 h
      postprandial glucose, fasting serum insulin, triglyceride, total cholesterol, and
      body mass index were assessed at pre-treatment, post-treatment, and follow-up,
      which was 2 months after treatment. RESULTS: The indices of the control group
      were not changed (P > 0.05) at the three time points. At the pre-treatment
      measurement, there were significant differences (P > 0.05) in indices among the
      three groups. At post-treatment, each index of the two groups was lower than that
      of the control group (P < 0.05), and improved in comparison with the pre
      treatment measurement (P < 0.05). In follow-up, each index of the aerobic
      exercise group and Acu-TENS group increased, but was still decreased compared
      with the pre-treatment value (P < 0.05), excluding body mass index. CONCLUSION:
      Acu-TENS could improve the state of patients with T2DM and be used as a therapy
      in clinical application.

PMID- 25975047
TI  - Frequency steps and compositions determine properties of nee- dling sensation
      during electroacupuncture.
AB  - OBJECTIVE: To investigate the relationship of electro-parameters and the
      electroacupuncture sensation (EAS), which is thought to be an important factor
      for optimal treatment. METHODS: The frequency steps and compositions of three
      frequently used electrical stimulations were set when the switch of the
      electroacupuncture apparatus was turned to the second or third grade of the dense
      disperse frequency wave (DD2 and DD3, respectively) or the second grade of the
      continuous wave (C2). Three groups of patients according to the three
      electroacupuncture stimulations were divided again into three sub-groups
      according to the stimulated acupoints: the face acupoint Quanliao (SI 18), the
      upper-limb acupoint Quchi (LI 11) and the back acupoint Dachangshu (BL 25). The
      EAS values were measured every 5 min during 30 min electroacupuncture treatments
      using a visual analogue scale. RESULTS: The frequency compositions of the three
      electroacupuncture stimulations were 3.3 and 33 Hz, 12.5 and 66.7 Hz, and 3.3 and
      3.3 Hz; each frequency step was 30, 54 and 0 Hz, respectively. In each sub-group
      of the C2 group, the EAS values from 10 to 30 min were significantly weaker than
      at 0 min. The sensation fluctuations in the DD2 and DD3 groups were different
      during the 30 min. CONCLUSION: The greater the frequency step of the
      electroacupuncture stimulation, the longer the needling sensation lasted. The
      electroacupuncture stimulations of the DD3 group were unsuitable for the facial
      acupoint because of its painful and uncomfortable EAS, but more suitable for the
      back acupoint.

PMID- 25975046
TI  - Effect of naringenin in Qianggu capsule on population pharmacokinetics in Chinese
      women with primary osteoporosis.
AB  - OBJECTIVE: To characterize naringenin (NAR) pop- ulation pharmacokinetics (PPK)
      in Chinese women with primary osteoporosis. METHODS: Ninety-eight female patients
      with primary osteoporosis from the Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen,
      and Donghuamen communities in Beijing, China, aged 40 to 80 years, re- ceived
      oral Qianggu capsules (250 mg). Blood samples were collected before and at 0.5,
      1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. The concentration of NAR
      in the blood samples was measured using high performance liquid chromatography
      tandem mass spectrometry. PPK analyses were performed with nonlinear mixed-effect
      modeling software (version 7.1.2, PsN3.2.12). The clearance (C1), central
      distribution volume (V), absorption rate constant (Ka1), peripheral distribution
      volume (VII), and inter-compartmental clearance (CLII) were set as parameters and
      estimated by the base model, covariate model, and final model. Kidney-Yang
      deficiency [Shenyangxu (SYAX)] and liver-kidney-Yin deficiency (Ganshenyinxu) are
      patterns of symptoms in Traditional Chinese Medicine that were set as covariates,
      along with age, height, blood urea nitrogen, serum creatinine, alanine
      transaminase, aspartate transaminase, and hyperlipidemia. Both stepwise forward
      and backward procedures were accomplished to build models. The final model was
      evaluated by internal and external validation, visual predictive check,
      bootstrap, and leverage analysis. RESULTS: A one compartment open model with
      first order degradation was the best fitted to the concentration-time profiles
      following oral administration of NAR. The mean of population parameters of the
      final model, C1, SYAX on C1, V, Ka1, CLII, and VII, were measured to be 37.6 L/h,
      0.427 L, 123 L/h, 0.12/h, 0.3056, and 1.446, respectively. Inter-individual
      variability was estimated and SYAX was identified as a significant covariate.
      CONCLUSION: The population pharmacokinetic model described in this study could
      effectively characterize the pharmacokinetic profile of NAR following
      administration of a single dose of oral Qianggu capsules in Chinese women with
      primary osteoporosis. Among the tested covariates, only SYAX was a significant
      factor.

PMID- 25975048
TI  - Effect of calycosin on left ventricular ejection fraction and angiogenesis in rat
      models with myocardial infarction.
AB  - OBJECTIVE: To evaluated the effect of calycosin on left ventricular ejection
      fraction and angiogenesis. METHODS: Adult male Sprague-Dawley rats were randomly
      assigned into calycosin-treated groups (0.5, 1, 2, and 4 mg/kg qd), a dimethyl
      sulfoxide (DMSO), or a sham-operated control group. The myocardial ischaemia (MI)
      model was intraperitoneally administered calycosin for 28 days. The survival
      rates and left ventricular ejection fractions (LVEF) were compared between
      groups. The expression levels of vascular endothelial growth factor (VEGF) and
      cluster of differentiation 31 (CD31) in ischaemic myocardium were also measured
      and compared. RESULTS: The construction of MI model resulted in a LVEF reduction
      of 50% compared with the sham-control. After 28 days, the LVEF value was 10%
      higher when calycosin (4 mg/kg) was administered compared with the DMSO group.
      The expression of VEGF and CD31 showed a dose-dependent manner when calycosin was
      administrated. The calycosin-treated (4 mg/kg) group displayed a two-fold
      increase in VEGF expression at both the mRNA and protein levels compared with the
      DMSO group. In addition, CD31 expression in the microvascular increased 1.5-fold
      in the 4 mg/kg calycosin-treated group. CONCLUSION: Calycosin improved left
      ventricular ejection fraction in the MI rat models, induced VEGF expression in
      the ischaemic myocardium, increased CD31 expression and promoted angiogenesis.

PMID- 25975049
TI  - [Genome wide expression analysis of the effect of Socheongryong Tang in asthma
      model of mice].
AB  - OBJECTIVE: To investigate the molecular effect of Socheongryong Tang (SCRT,
      Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by
      microarray technology. METHODS: Asthma was induced by intranasal instillation of
      ovalbumin in mouse. After administration of SCRT on asthma-induced mouse, the
      expression of genes in lung tissue was measured using whole genome microarray.
      The functional implication of differentially expressed genes was performed using
      ontological analysis and the similarity of promoter structure of genes was also
      analyzed. RESULTS: Treatment of SCRT restored expression level of many up- or
      down-regulated genes in asth- ma model, and this recovery rate means SCRT could
      regulate a set of genes having specific TFBS binding sites. CONCLUSION: In this
      study, we identified a set of genes subjected to similar regulation by SCRT in
      asthma model in mice.

PMID- 25975050
TI  - Effects of therapies for regulating and reinforcing lung and kidney on
      osteoporosis in rats with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the efficacy and long-term effects of the three therapies
      for regulating and reinforcing lung and kidney (reinforcing lung and invigorating
      spleen, reinforcing lung and replenishing kidney, and supplementing Qi and
      nourishing kidney) in Traditional Chinese Medicine (TCM) on osteoporosis in rats
      with chronic obstructive pulmonary disease. METHODS: Totally 120 rats were
      randomly divided into control, model, Bufeijianpi, Bufeiyishen, Yiqizishen,
      aminophyline groups. Repeated smoke inhalations and bacterial infections were
      used to duplicate the stable Chronic obstructive pulmonary disease rat model.
      Normal saline was given to the air control and model groups, while Bufeijianpi
      granule, Bufeiyishen granule, and Yiqizishen granule, and aminophylline were
      administrated to rats in the Bufeijianpi, Bufeiyishen, Yiqizishen, and
      aminophylline groups respectively from weeks 9 through 20. Another 12 weeks
      without medicines to observe the long-term effect. Rats were sacrificed at week
      20 and week 32. Bone mass density (BMD), bone mineral content (BMC), morphology
      of the femoral head, lung function, and levels of serum interleukin (IL)-1beta,
      IL-6, and tumor necrosis factor-alpha were detected. RESULTS: At weeks 20 and 32,
      tidal volume, peak expiratory flow and expiratory flow at 50% tidal volume in the
      three TCM-treated groups were higher than those in the model group (P < 0.05).
      Femur weight, BMD, and BMC were significantly higher in the three TCM-treated
      groups and the aminophylline-treated group compared with the model group (P <
      0.01), except for BMC in the Yiqizishen-treated group at week 20. CONCLUSION:
      Bufeijianpi, Bufeiyishen, and Yiqizishen granules show good effects in the
      prevention and treatment of osteoporosis, which can alleviate airflow limitations
      and inflammation, improve BMD and BMC of the femur, and have favorable long-term
      effects.

PMID- 25975051
TI  - Effect of Bushenwenyanghuayu decoction on nerve growth factor and
      bradykinin/bradykinin B1 receptor in a endometriosis dysmenorrhea mouse model.
AB  - OBJECTIVE: To observe the effects of Bushenwenyanghuayu decoction (BD), a
      Traditional Chinese Medicine (TCM), on the serum concentration of nerve growth
      factor (NGF) and bradykinin (BK), and protein and mRNA levels of NGF and
      bradykinin B1 receptor (BKB1R) in a mouse model of endometriosis dysmenorrhea.
      METHODS: Seventy-five experimental female BALB/c mice were randomly divided into
      five groups, 15 mice each: sham, model, BD high dose (61.67 g/kg), BD low dose
      (15.42 g/kg), and gestrinone (0.4 mg/kg) groups. All the mice except for those in
      the sham group underwent auto-transplantation surgery and were gavaged estradiol
      valerate (0.5 mg/kg, daily for 12 days) after surgery. On the 12th day, 1 h after
      administration, writhing response was induced by intraperitoneal injection of
      oxytocin at 2 U/mouse. The writhing frequency and latency were recorded and the
      volume of the ectopic foci was measured. The concentration of serum NGF and BK
      was detected by enzyme-linked immunosorbent assay, the protein expression of NGF
      and BKB1R was tested by immunohistochemistry and western blotting, and NGF and
      BKB1R mRNAs were detected by real-time PCR. RESULTS: Compared with the model
      group, the volume of the ectopic foci in the treatment groups was significantly
      lower (P < 0.01), the writhing frequency was decreased (P < 0.05), and the
      writhing latency was prolonged (P < 0.01). Compared with the sham group, serum
      NGF and BK levels in the model group were significantly increased (P < 0.01).
      There were positive correlations for writhing frequency among the NGF and BK
      groups (P < 0.01). The serum NGF and BK levels were significantly lower in the
      treatment groups than the model group (P < 0.05). The protein expression of NGF,
      BKB1R was significantly decreased in the treatment groups compared with the model
      group (P < 0.01). NGF and BKB1R mRNA expression was significantly decreased in
      the treatment groups compared with the model group (P < 0.01). CONCLUSION: NGF
      and BK/BKB1R may play an important role in the development of endometriosis
      associated dysmenorrhea, and BD was found to inhibit the development of
      endometriosis and relieve dysmenorrhea by influencing NGF and BK/ BKB1R mRNA and
      protein levels.

PMID- 25975052
TI  - Effect of Bushenhuoxue formula on interleukin-1 beta and discoidin domain
      receptor 2 levels in a rat model of osteoarthritis.
AB  - OBJECTIVE: To determine the effects of Bushenhuoxue formula (BHF) on interleukin
      1 beta (IL-1beta), transforming growth factor beta 1 (TGF-beta1), discoidin
      domain receptor 2 (DDR2) and matrix metalloproteinase-1 (MMP-1) levels in a rat
      model of osteoarthritis (OA). METHODS: Sprague-Dawley rats were used to establish
      an OA model and subjected to various treatments over 6 weeks. Rats were treated
      with BHF, glucosamine sulfate (GS), or starch as a control. Serum levels of IL
      1beta and MMP-1 and joint fluid levels of IL-1beta were determined by means of
      ELISAs. We used immunohistochemistry to determine DDR2 levels in knee cartilage.
      Gene expression levels of MMP-1 in joint synovial tissue were assessed using
      reverse transcription polymerase chain reaction assays. RESULTS: Serum IL-1beta
      levels were unchanged throughout the study. Levels of IL-1beta in joint fluid and
      MMP-1 in sera from the BHF- and GS-treated groups were significantly reduced.
      DDR2 levels in knee cartilage were also significantly reduced in the BHF group.
      Expression of the MMP-1 gene was significantly reduced by BHF treatment.
      CONCLUSION: BHF might be beneficial in the inhibition and alleviation of local
      inflammatory responses and cartilage degeneration in OA.

PMID- 25975053
TI  - Effect of Yajieshaba, a preparation of Dai indigenous medicine, on enhanced liver
      detoxification.
AB  - OBJECTIVE: To explore the mechanistic effects of Yajieshaba (YJSB) on enhanced
      liver detoxification. METHODS: The effects of YJSB on alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) were assayed in five acute chemical
      liver injury models [carbon tetrachloride (CCl4), D-galactosamine (D-Glan), 4
      acetamidophenol (AAP), thioacetamide (TAA) and 1-naphthyl isothiocyanate (ANIT)].
      Sleep latency and sleep time of pentobarbital sodium were tested in control mice
      and CCl4 model miceafter oral YJSB administration. The effects of YJSB on drug
      metabolism enzymes of liver microsomes were tested in control rats and CCl4 model
      rats. The levels of cytochrome P450 (CYP450) and Cyt b5 in liver microsomes were
      assayed using the method by Omura and Sato, and activities of erythromycin N
      demethylase (ERD) and aminopyrine N-demethyl (ADM) were evaluated by Nash
      colorimetry. Probe substrate-based high performance liquid chromatography (HPLC)
      methods were established for CYP3A4 and CYP1A2. RESULTS: The level of serum ALT
      was reduced by YJSB at 3.51 g/kg in the five models as follows: CCl4 > D-Glan,
      AAP, ANIT > TAA. YJSB treatment did not reduce the level of serum AST. YJSB at
      3.51 g/kg prolonged the sleep latency in control mice and shortened the sleep
      time of control mice and CCl4 model mice. For control rats, YJSB at 2.43 g/kg
      increased the levels of CYP450 and Cyt b5 and induced the activities of ERD and
      ADM; for liver injuries induced by CCl4 in rats, YJSB at 2.43 g/kg increased the
      levels of CYP450 and Cyt b5. These results suggest that YJSB at 2.43 g/kg induces
      CYP3A4 and CYP1A2. CONCLUSION: These results suggest that YJSB enhanced liver
      detoxification and the mechanisms may be partially related to CYP3A4 and CYP1A2
      induction.

PMID- 25975054
TI  - Pharmacokinetic investigation on interaction between hydrophilic lithospermic
      acid B and lipophilic tanshinone IIA in rats: an experi- mental study.
AB  - OBJECTIVE: To elucidate the interaction between hydrophilic lithospermic acid B
      and lipophilic tanshinone II A in rats. METHODS: A reliable high-performance
      liquid chromatography method was adopted for simultaneous determination of
      lithospermic acid B and tanshinone II A in rat plasma, through which the
      pharmacokinetic interaction between lithospermic acid B and tanshinone II A by
      intravenous injection was investigated. RESULTS: The simultaneous intravenous
      injection of tanshinone II A and lithospermic acid B significantly altered the
      pharmacokinetic parameters of both compounds when compared with the individual
      intravenous administration of each compound. The area under the concentration
      time curve of tanshinone II A and lithospermic acid B increased by 18.35 and
      59.31%, respectively. The mean retention time of tanshinone II A and lithospermic
      acid B increased, respectively, from 9.3 to 32.8 h and 20.2 to 49.1 h. The
      concomitant use of tanshinone II A magnified the volume of distribution at steady
      state (Vss) and time for the drug in the plasma to reduce the highest
      concentration by half (t1/2) of lithospermic acid B, while at the same time the
      Vss and t1/2 of tanshinone II A changed significantly in the presence of
      lithospermic acid B. CONCLUSION: Lithospermic acid B and tanshinone II A interact
      with each other following simultaneous intravenous injection in rats and this
      observation may expand the clinical use of Danshen (Radix Salviae Miltiorrhizae).

PMID- 25975055
TI  - Effects of different Chinese herbal prescriptions on cytokines in au- toimmune
      prostatitis rats.
AB  - OBJECTIVE: To observe and compare the effects of Chinese herbal prescriptions for
      promoting blood circulation, clearing heat, removing toxicity, and dispersing
      stagnated liver-Qi on cytokines in mode rats with experimental autoimmune
      prostatitis (EAP) to provide an experimental basis for the use of Chinese herbal
      prescriptions in the treatment of chronic prostatitis. METHODS: One-hundred and
      ten male Wistar rats were randomly divided into 11 groups: blank group; model
      group; Huoxuehuayu (promoting blood circulation to remove blood stasis) high,
      middle, and low dose groups; Qingrejiedu (clearing heat and removing toxicity)
      high, middle, and low dose groups; and Shuganliqi (dispersing stagnated liver-Qi)
      high, middle, and low dose groups. Except the blank group, rats in all groups
      were injected subcutaneously in multiple points on days 0 and 30 with prostatic
      protein extractive solution (60 mg/ mL), and intraperitoneally injected with
      diphtheria-pertussis and tetanus vaccine (DPT vaccine) to establish the EAP
      model. Model rats were adminis- trated high, middle, and low doses of Chinese
      herb- al prescriptions and were sacrificed after 4 weeks. Pathological changes in
      the prostate gland were observed with HE staining and changes in serum
      interleukin-6 (IL-6), interleukin-8 (IL-8), and prostaglandin E2 (PGE2) levels
      were detected with enzyme-linked immunosorbent assay. RESULTS: Compared with the
      blank group, serum PGE2, IL-6, and IL-8 levels in the model group were
      significantly higher (P < 0.05). Compared with the model group, serum PGE2, IL-6,
      and IL-8 levels in the Qingrejiedu low dose and middle dose groups were
      significantly lower (P < 0.05), with the lower dose having a more obvious effect.
      Serum PGE2, IL-6, and IL-8 levels in the Huoxuehuayu high dose group (P < 0.05),
      IL-6 and IL-8 levels in the Huoxue- huayu middle dose group (P < 0.05), and the
      IL-8 level in the Huoxuehuavu low dose group were significantly lower than those
      in the model group (p < 0.05). There were significant differences in PGE2 and IL
      6 levels among the different dose groups of Shuganliqi drugs (P < 0.05). Compared
      with the model group, serum PGE2, IL-6, and IL-8 levels in the Shuganliqi high
      dose group (P < 0.05) and IL-8 level in the Shugangliqi low dose group were
      significantly lower (P < 0.05), while the Shuganliqi middle dose group did not
      change significantly. CONCLUSION: Therefore, in TCM treatment of autoimmune
      prostatitis, different treatment methods should select different doses. For
      prescriptions that clear heat and remove toxicity, low doses should be used. For
      prescriptions that promote blood circulation to remove blood stasis and for
      prescriptions that disperse stagnated liver-Qi, high doses should be used.

PMID- 25975056
TI  - Effect of a combination of calorie-restriction therapy and Lingguizhugan
      decoction on levels of fasting blood lipid and inflammatory cytokines in a high
      fat diet induced hyperlipidemia rat model.
AB  - OBJECTIVE: To combine calorie-restriction therapy (CRT) with Traditional Chinese
      Medicine (TCM) using Lingguizhugan Decoction and note the effects on expression
      of inflammatory cytokines [tumor necrosis factor (TNF)-alpha, high-sensitivity C
      reactive protein (hs-CRP), interleukin (IL)-6] in high-fat-diet induced
      hyperlipidemia in rats. METHODS: Forty rats were divided randomly and equally
      into four groups: control group A (regular feeding for 5 weeks); model group B
      (high-fat diet for 5 weeks), calorie-limited group C (high-fat diet for 5 weeks)
      and TCM calorie-limit group D (high-fat diet for 5 weeks). After modeling, groups
      C and D were fasted for 3 days: group C with simple fasting, and group D with TCM
      fasting. The motion as well as changes in color, body weight, food intake, plasma
      lipids [low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein
      cholesterol, total cholesterol (TC) and triglyceride (TG) along with TNF-alpha,
      hs-CRP and IL-6] were measured before and after intervention. RESULTS: Modeled
      rats were established after five weeks. After 3 days of fasting, compared with
      group B, blood lipid levels (TG, TC, LDL-C) of groups C and D decreased
      dramatically. Those of group D decreased more obviously than those of group C.
      However, the values of TNF-alpha, hs-CRP and IL-6 showed no obvious difference
      between each of the three treatment groups. CONCLUSION: CRT can reduce fasting
      blood lipid levels in rats, but not by reducing the levels of inflammatory
      cytokines.

PMID- 25975057
TI  - Protein and RNA expression of acid-sensing ion channels 2 and 3 in myocardial
      ischemia rats induced by isoproterenol.
AB  - OBJECTIVE: To investigate the impact of electro-acupuncture at the Neiguan (PC 6)
      acupoint on protein and RNA expression of acid-sensing ion channel 2 (ASIC2) and
      ASIC3 in myocardial ischemia rats. METHODS: Fifty male Sprague-Dawley rats were
      used, weighing (230 +/- 50) g. The rats were randomized into a normal group A,
      model group B, Neiguan (PC 6) group C, Lieque (LU 7) group D, and A-shi points
      group E. There were 10 rats in each group. Rats were continuously administered 85
      mg/ kg intravenous isoproterenol daily to establish the model. Successfully
      modeled rats in groups C, D, and E were given electro-acupuncture treatment. Each
      group of rats was sacrificed with chloral hydrate (1 mL/100 g) intraperitoneal
      injection. The left ventricular myocardium was extracted and placed at -70 
      degrees C until use. Western blot analysis and real-time PCR were performed to
      assay protein and RNA expressions of ASIC2 and ASIC3, respectively. Fold changes
      in RNA expression were quantified with the 2^ (-DeltaDeltaCt) method. Blood
      samples were drawn from the aorta abdominalis and tested for creatine kinase-MB
      (CK-MB) and lactate dehydrogenase (LDH) levels using enzyme-linked immunosorbent
      assay. RESULTS: Myocardial ischemia rats given electro-acupuncture at the Neiguan
      (PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and
      ASIC3, and CK-MB and LDH levels, compared with model rats (P < 0.01). CONCLUSION:
      Electro-acupuncture at the Neiguan (PC 6) acupoint can not only decrease the
      protein and RNA expression of ASIC2 and ASIC3, but also inhibit the opening of
      ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.

PMID- 25975058
TI  - Effect of manual acupuncture on bowel motility in normal kunming mouse.
AB  - OBJECTIVE: To observe the effects of acupuncture on motility of jejunum and
      distal colon at different acupoints on normal Kunming mice. METHODS: The jejunal
      and colorectal motor activity of forty Kunming mice were recorded by the intra
      intestinal capsule. The capsules contained with distilled water were placed into
      the cavities of jejunum and distal colon. The changes of bowel were compared with
      the background activity recorded before any stimulation. The chosen acupoints
      were as follows: Zusanli (ST 36) on the lower legs, Tianshu (ST 25) on the mid
      lower abdomen. RESULTS: Manual acupuncture (MA) at Zusanli (ST 36) significantly
      promoted the motility of jejunum and distal colon (manifested as increased change
      rate of average amplitude and increased change rate of mean area under the
      contractile curve) of normal Kunming mice (P < 0.01). MA at Tianshu (ST 25)
      significantly inhibited the motility of jejunum (manifested as decreased change
      rate of average amplitude, decreased change rate of mean area under the
      contractile curve, and the reduced frequency) of normal Kunming mice (P < 0.01),
      while significantly increased the distal colonic motility (manifested as
      increased amplitude and increased mean area under the contractile curve) of
      normal Kunming mice (P < 0.01). CONCLUSION: MA at specific acupoints [Zusanli (ST
      36), Tianshu (ST 25)] has different effects on the motility of jejunum and distal
      colon, which might involve the segmental innervations of the related nerve.

PMID- 25975059
TI  - Effect of lit-moxa stimulation of Guanyuan (CV 4) acupoint on levels of lactic
      acid and superoxide dismutase in skeletal muscle of rats.
AB  - OBJECTIVE: To observe the effect of lit-moxa stimu- lating acupoint Guanyuan (CV
      4) on lactic acid and super-oxide dismutase (SOD) in skeletal muscle after
      exercise exhaustion. METHODS: Twenty-eight adult male Sprague-Dawley rats were
      randomly divided into normal control group, exhausted control group, exercise
      group and moxibustion group using exercise training and mild heating with lit
      moxa stick as treatment methods. The exhausted control group, moxibustion group
      and exercise group received an exhaustive swimming after 20 days of intervention.
      Swimming exhausted times were recorded. Lactic acid and SOD concentration in
      soleus muscle were detected and compared between every two groups. RESULTS: The
      swimming exhausted times of the moxibustion group and the exercise group were
      significantly increased compare to the exhausted control group (P < 0.05). The
      lactic acid of the exhausted control group was significantly increased comparing
      with the normal control group (P < 0.05), and the lactic acid of the moxibustion
      group and the exercise group were significantly lower than that of the exhausted
      control group (P < 0.05). The SOD level of the exhausted control group was
      significantly decreased comparing with the normal control group (P < 0.05), and
      the SOD level of the moxibustion group and the exercise group were significantly
      higher than that of the exhausted control group (both, P < 0.05). There was no
      statistical difference between the moxibustion group and the exercise group.
      CONCLUSION: With lit moxa stick, heat stimulating acupoint of Guanyuan (CV 4)
      decreased the levels of lactic acid and SOD in rat's skeletal muscle.

PMID- 25975061
TI  - Asymptomatic stage of human immunodeficiency virus infection is the optimal
      timing for its management with Traditional Chinese Medicine.
AB  - Acquired immune deficiency syndrome (AIDS) is a worldwide public health problem
      and an incurable disease. The roles of Traditional Chinese Medicine (TCM) on AIDS
      had been recognized and accepted by more and more people. Being a relatively long
      period, to initiate combination antiretroviral therapy (cART) for the
      asymptomatic human immunodeficiency virus (HIV) infection patient is not
      consensus. According to TCM theory, not only the imbalance of Yin and Yang but
      also the disharmony of internal body function and external natural environment
      had occurred in the body of the patient, the imbalance and the disharmony should
      be adjusted by the means of the treatment based on the patters identified among
      the symptoms in terms of TCM. We aimed to analyze the feature of patients with
      asymptomatic infection, and compare the advantages and disadvantages of the us-
      age of cART for asymptomatic infection, explored the possible mechanism
      underlying TCM treatment of the asymptomatic infection, by reviewing the TCM
      treatment progress on asymptomatic HIV infection.

PMID- 25975062
TI  - How to improve oral health in Africa? What is the situation in Nigeria? Two
      articles shed light on the subject.

PMID- 25975060
TI  - [Regulatory mechanism of hormones of the pituitary-target gland axes in kidney
      Yang deficiency based on a support vector machine model].
AB  - OBJECTIVE: To study the development mechanism of kidney-Yang deficiency through
      the establishment of support vector machine models of relevant hormones of the
      pituitary-target gland axes in rats with kidney-Yang deficiency syndrome.
      METHODS: The kidney-Yang deficiency rat model was created by intramuscular
      injection of hydrocortisone, and contents of the hormones of the pituitary
      thyroid axis: thyroid stimulating hormone (TSH), 3,3',5-triiodothyronine (T3) and
      thyroxine (T4); hormones of the pituitary-adrenal gland axis: adrenocorticotropic
      hormone (ACTH) and cortisol (CORT); and hormones of the pituitary-gonadal axis:
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone
      (T), were determined in the early, middle, and advanced stages. Ten support
      vector regression (SVR) models of the hormones were established to analyze the
      mutual relationships among the hormones of the three axes. RESULTS: The feedback
      control action of the pituitary-adrenal axis began to lose efficacy from the
      middle stage of kidney-Yang deficiency. The contents all hormones of the three
      pituitary-target gland axes decreased in the advanced stage. Relative errors of
      the jackknife test of the SVR models all were less than 10%. CONCLUSION:
      Imbalances in mutual regulation among the hormones of the pituitary-target gland
      axes, especially loss of effectiveness of the pituitary-adrenal axis, is one
      pathogenesis of kidney-Yang deficiency. The SVR model can accurately reflect the
      complicated non-linear relationships among pituitary-target gland axes in rats
      with of kidney-Yang deficiency.

PMID- 25975063
TI  - Stratification in anterior teeth using one dentine shade and a predefined
      thickness of enamel: a new concept in composite layering--Part II.
AB  - While restoring an anterior tooth, shade matching is one of the crucial points
      that we can face to have an esthetic final outcome. After studying the physical
      and optical characteristics of enamel and dentine in the first part of this
      article, the second part will propose a new method for color matching and a
      clinical stratification using a simple and reproducible procedure for anterior
      restorations with only one dentine and one enamel shade.

PMID- 25975064
TI  - [Morphometric study of total edentulous maxilla of Moroccan subjects].
AB  - Despite the importance of taking the primary dental impression, this act remains
      unfortunately neglected by most practitioners. Think to succeed a total removable
      prosthesis from a failed primary dental impression is a challenge for the
      practitioner and seems utopia. For this, you wish through our work give the
      importance to the choice of the mass-produced impression tray that is paramount
      for the success of the primary dental impression. This study examines a sample of
      160 plaster primary models (80 maxillary and 80 mandibular) from primary dental
      impression carried out with mass-produced impression trays whether or not
      modified for new total edentulous patients having consulted at the University
      Dental centre in Casablanca for a prosthetic rehabilitation by total prosthesis.
      Thirty-six women and 44 men have been selected. The study showed that men have
      maxillary and mandibular arches longer and wider than those of women, and that
      the average value for several parameters measured is close to the measurements of
      the maxilla trays U3 and mandibular L3; Where the need for acquisition of large
      size dental impression tray, in accordance with the dimensions of our population
      in order to meet our expectations, namely: to respect the integrity of the
      support surfaces, to meet the mechanical qualities of the prosthesis, to restore
      the aesthetics and function by minimizing the grievances of the toothless total
      subject.

PMID- 25975065
TI  - [Evaluation of the professional dentists' ability to determine the tooth shade
      guide: a pilot study].
AB  - BACKGROUND: During its clinical practice, the dentist is often faced with issues
      concerning the determination of teeth shade. This step is considered sensitive by
      numerous clinicians and dental laboratories. The objective of this study was to
      test the ability of professional dentists to visually determine the teeth color.
      MATERIAL AND METHODS: Eleven dentists classified 35 unmarked samples according to
      their hue, chroma and value from 2 standardized tooth shade guides Ivoclar
      Vivadent (Chromascop) et Vita (3D Master). The ratio between the number of
      matching samples and the total amount of samples from each group was calculated
      and converted to a score between 0 and 10. RESULTS: Better scores were obtained
      for value and chroma with the 3D Master shade guide than with the Chromascop
      shade guide (p < 0.001). The opposite result was obtained for the hue (p < 0.05).
      Globally, better results were obtained for the value and chroma, the hue being
      the most difficult item to evaluate. A satisfying "color perception" was observed
      in 69% of the cases. CONCLUSION: The results of this study argue in favor of a
      specific training for tooth shade determination in Odontology.

PMID- 25975066
TI  - Antibiotics prescription in Nigerian dental healthcare services.
AB  - INTRODUCTION: Inappropriate antibiotics prescription in dental healthcare
      delivery that may result in the emergence of antibiotic-resistant bacteria, is a
      worldwide concern. The objective of the study was to determine the antibiotics
      knowledge and prescription patterns among dentists in Nigeria. MATERIALS AND
      METHODS: A total of 160 questionnaires were distributed to dentists attending
      continuing education courses organized by two organizations in Southern and
      Northern parts of Nigeria. Data analysis was done using SPSS version 17.0.
      RESULTS: A total of 146 questionnaires were returned, properly filled, out of 160
      questionnaires, giving an overall response rate 91.3%. The clinical factors
      predominantly influenced the choice of therapeutic antibiotics among the
      respondents. In this study, the most commonly prescribed antibiotics among the
      respondents was a combination of amoxicillin and metronidazole. Of the
      respondents, 136 (93.2%) of them considered antibiotic resistance as a major
      problem in Nigeria and 102 (69.9%) have experienced antibiotics resistance in
      dental practice. The major reported conditions for prophylactic antibiotics among
      the respondents were diabetic mellitus, HIV/AIDS, history of rheumatic fever,
      other heart anomalies presenting with heart murmur and presence of prosthetic
      hip. The knowledge of adverse effects of antibiotics was greatest for tooth
      discoloration which is related to tetracycline. CONCLUSION: Data from this study
      revealed the most commonly prescribed antibiotics as a combination of amoxicillin
      and metronidazole. There existed gaps in prophylactic antibiotic prescription,
      consideration in the choice of therapeutic antibiotics and knowledge of adverse
      effects of antibiotics among the studied dentists.

PMID- 25975067
TI  - Third molars emergence status among 15 to 16 year-old Tanzanian youths.
AB  - BACKGROUND: Adequate knowledge of timing and pattern of the third molars is
      essential. The molars are often used to supplement human maturity indicators for
      school attendance, social benefits, employment, and marriage, differentiating the
      juvenile from the adult's status in criminal law cases, unidentified cadavers and
      human remains when birth records are not adequate or not available. BROAD
      OBJECTIVE: The study was carried out to investigate the emergence status of the
      third molar tooth among 15 to 16 year-old Tanzanian adolescents. METHODOLOGY: A
      cross-sectional community based study was carried out among secondary school
      children in Ilala District, Dar es Salaam, Tanzania. This study included 203
      adolescents aged 15-16 years old of whom 54% were boys and 46% girls. It was a
      subsample of randomly selected Tanzanian youths who were part of a larger sample
      of 869 children from randomly selected 16 schools from different parts of the
      district covering the whole range of socio-economic background. RESULTS: More
      third molars were already in occlusion in girls (11-13%) than in boys (3-4%)
      while girls had more third molars emerged into the oral cavity than boys did. The
      girls had about 15% to 20% of the four third molar teeth emerged in the oral
      cavity compared to about 3% to 18% in boys. Except for the mandibular right third
      molar, all the differences in emergence of the third molars between girls and
      boys were statistically significant. More mandibular third molars had emerged
      than the corresponding maxillary ones. DISCUSSION AND CONCLUSIONS: Third molars
      were in occlusion in 3-13% of the Tanzanian youths aged 15-16 years indicating
      earlier emergence than in Caucasian populations. Hence, the need for specific
      third molars emergence standard tables molars is evident. More studies both cross
      sectional and longitudinal type involving a larger sample to provide the median
      and mean ages, rate and pattern of emergence of the third molars in the Tanzanian
      youth populations are recommended.

PMID- 25975068
TI  - Basic package of oral care: a veritable tool for promotion of primary oral health
      care by community health officers.
AB  - OBJECTIVES: Primary health care workers have the educational and clinical
      capacity required to learn basic package of oral care and become the primary
      resource for oral health promotion and simple curative care in their communities.
      The study was undertaken to determine the willingness of community health
      officers to treat patient with oral complaints, receive training on basic oral
      treatment and comment on basic package of oral care in the promotion of oral
      health. METHODS: Data were collected using self-administered questionnaires. The
      questionnaires were peer-reviewed for content validity and revised before data
      collection. Analysis was done using SPSS-16 statistical software. Proportions
      were compared using Chi-square test at 95% confidence interval. RESULTS: All the
      participants reported seeing patients with oral complaints. About 60% of the
      participants saw less than 5 patients with oral complaints per week, while 27.3%
      saw between 5-10 patients per week. Two-third (66.7%) and 18.2% of the patients
      visited the health centres for pain and multiple complaints respectively. About
      90% of the health workers were willing to receive training on basic oral
      treatment and provide treatment for patients with dental complaints. CONCLUSION:
      The expressed desire by the community health officers to learn basic oral
      treatment and provide treatment for the dental population in their local
      community; is an indication that this group of staff may be used to bridge the
      existing inequalities in oral health and contribute to the promotion of oral
      health.

PMID- 25975069
TI  - Prematurity Is preventable.

PMID- 25975070
TI  - Marion's message. Take a deep breath.

PMID- 25975071
TI  - Prematurity and creativity.

PMID- 25975072
TI  - What I have learned about premature birth.

PMID- 25975073
TI  - Elizabelb Cellier: a midwife of seventeenth-century London.

PMID- 25975074
TI  - Evidence, eminence and opinion: a brief reflection on knowledge.

PMID- 25975076
TI  - An introduction to meconium.

PMID- 25975075
TI  - Tribute to a Maverick. Stephen Gaskin . 1935-2014.

PMID- 25975077
TI  - Sharon Evans, loved and remembered.

PMID- 25975078
TI  - Malnutrition, unhealthy lifestyles and scheduled deliveries: the causes of
      prematurity.

PMID- 25975079
TI  - Prematurity and kangaroo care during a disaster.

PMID- 25975080
TI  - Two of my birth stories.

PMID- 25975081
TI  - Journey with a birth theme.

PMID- 25975082
TI  - Why aren't more breech babies Born at home? A student midwife's perspective.

PMID- 25975083
TI  - Diet du jour! Pregnancy and popular diets.

PMID- 25975084
TI  - The birth of Mariposa: a fictional story.

PMID- 25975085
TI  - Update on Belize, Central America.

PMID- 25975086
TI  - Permission to practice self-compassion.

PMID- 25975087
TI  - CBAC and acceptance: the birth story of Rumi.

PMID- 25975088
TI  - Thoughts from the ICM conference.

PMID- 25975089
TI  - Responses to issue 110.

PMID- 25975090
TI  - What do you see as the role of fathers in pregnancy, labor and/or birth?

PMID- 25975091
TI  - The autoimmune pathogenesis of multiple sclerosis.
AB  - One of the major goals of biomedical research is to reveal the pathomechanisms
      that lead to a disease on a level on which diagnostic criteria and causal
      therapies can be designed. The understanding and treatment of multiple sclerosis
      (MS) is still far from this goal, but exciting developments are on the way. MS is
      thought to be an autoimmune disease that is mediated by brain tissue-reactive
      lymphocytes, T cells and B cells, but so far these lymphocytes could not be
      reliably detected. This article highlights recent developments that permit the
      detection of autoreactive B cells in MS, the implications of this finding for
      early diagnosis of the disease, monitoring its activity, and eventually for
      gaining insight into the specific immune pathology that drives MS.

PMID- 25975092
TI  - High dose of epigallocatechin-3-gallate inhibits proliferation and induces
      apoptosis of H9C2 cardiomyocytes through down-regulation of SIRT1.
AB  - BACKGROUND: Previous studies have suggested that high doses of (-)
      epigallocatechin-3-gallate (EGCG) can induce toxicity in the liver, kidneys, and
      intestine. However, there have been no reports of myocardiotoxicity following
      treatment with EGCG. In this study, we investiged the proliferation and apoptosis
      of H9C2 cardiomyocytes treated with high dose of EGCG. METHODS: Cell
      proliferation was measured by CCK8 assay, cell apoptosis rate was evaluated by
      TUNEL assay, and the expression alterations of Sirtuin 1 (SIRT1) protein was
      detected by Western blotting. RESULTS: EGCG inhibits proliferation and induces
      apoptosis in time- and dose-dependent manner in H9C2 cardiomyocytes. SIRT1
      participates in the inhibitory effect of EGCG on cell proliferation and apoptosis
      induction in H9C2 cardiomyocytes. CONCLUSION: This study demonstrates that high
      doses of EGCG inhibit proliferation and induce apoptosis in H9C2 cardiomyocytes.
      Down-regulation of SIRT 1 protein expression may be involved.

PMID- 25975093
TI  - Neuroprotective effects of torularhodin against H2O2-induced oxidative injury and
      apoptosis in PC12 cells.
AB  - The neuroprotective effects of torularhodin against oxidative injury and
      apoptosis in PC12 cells, as well as the related mechanisms, were investigated.
      The results showed that torularhodin significantly reduced lactate dehydrogenase
      (LDH) release and malondialdehyde (MDA) production, meanwhile increased the
      activities of antioxidant enzymes, which were assessed by enzyme linked
      immunosorbent assay. The presence of torularhodin attenuated H2O2-induced
      apoptosis which was proven by flow cytometric detection of Ca2+ influx inhibition
      and the mitochondrial membrane potential (MMP) reduction. Furthermore, the
      oxidative injury produced by H2O2 was mitigated by torularhodin pretreatment via
      down-regulation of GSK-3beta and Keap1 genes while up-regulating the expressions
      of Nrf2, HO-1 and NQO1 genes. The neuroprotective effects of torularhodin against
      oxidative injury and apoptosis appeared to be associated with the synergistic
      effect of mitochondria-mediated pathway and GSK-3beta/ Nrf2 signaling pathway.
      These findings demonstrated that torularhodin could be considered as a
      neuroprotective agent against H2O2-induced oxidative stress.

PMID- 25975094
TI  - Therapeutic effects of the soluble epoxide hydrolase (sEH) inhibitor AUDA on
      atherosclerotic diseases.
AB  - In this study, we aimed to detect the effects of the soluble epoxide hydrolase
      (sEH) inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) on
      atherosclerotic diseases and to explore its mechanism. The atherosclerosis animal
      model was constructed by ApoE-/- mice. To determine the optimal therapeutic
      concentration of AUDA, different concentrations of AUDA were infused into ApoE-/-
      mice, with controls receiving infusions of normal saline alone. Mouse body weight
      and serum total cholesterol, triglyceride, LDL and HDL levels were measured. The
      western blotting (WB) method was used to detect the expression of TLR4 and NFKB
      in the aortic wall of the AUDA-treated and control mice. After the animals were
      sacrificed, we performed Oil Red O staining of the aortic sinus atherosclerotic
      plaque area followed by quantitative analysis of the aortic atherosclerotic
      plaque size and the percentage of lumen area in the two groups of mice. The
      expression levels of inflammatory cytokines, adhesion molecules and chemokines in
      the AUDA group were significantly decreased compared to the saline-treatment
      group (P < 0.05). The optimal AUDA concentration was found to be 0.35 ml/mg. AUDA
      significantly inhibited the expression of TLR4 and NFkappaB in ApoE-/- mouse
      aortas and reduced the aortic sinus plaque area of the ApoE-/- mouse group (P <
      0.05). In conclusion, AUDA can regulate blood lipid balance, which may be one of
      the mechanisms for its protective effects on the cardiovascular system.

PMID- 25975095
TI  - Schisandrin A and B induce organic anion transporting polypeptide 1B1 transporter
      activity.
AB  - Organic anion transporting polypeptide 1B1 (OATP1B1) is the most important
      transporter in the organic anion transporting polypeptide family. OATP1B1 plays
      an important role in the hepatic uptake of many endogenous compounds and
      xenobiotics, including many clinical drugs. At present, the combinational usage
      of Chinese traditional herbal medicines and conventional chemical pharmaceuticals
      may affect the activity of enzymes and transporters activity and cause absorption
      of their substrates and metabolic changes. In this study, we aimed to investigate
      the effect of schisandrin A, schisandrin B and tanshinone IIA, which were
      extracted from medicinal plants, on OATP1B1 activity. HepG2 cells are used as in
      vitro models for OATP1B1 activity studies. A combination of 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assays, real-time
      RT-PCR, and transporter activity analysis were employed. We found that
      schisandrin A and B increased OATP1B1 mRNA levels by 1.81-fold (p < 0.01) and
      1.87-fold (p < 0.01) at concentration of 10 MUM, respectively. Schisandrin A of 1
      MUM and 10 MUM and schisandrin B of 10 MUM significantly increased the uptake of
      [3H] estrone-3-sulfate (p < 0.05 or p < 0.01). Tanshinone IIA had no effect on
      the mRNA expression and transport activity of OATP1B1 at nontoxic concentrations.
      Our study suggests that schisandrin A and B induced OATP1B1 expression and
      increased its transporter activity in HepG2 cells.

PMID- 25975096
TI  - 293FT is a highly suitable mammalian cell line for the in vitro enzymatic
      activity analysis of typical P450 proteins.
AB  - Mammalian cells have been widely used for the in vitro evaluation of the
      functional effect of allelic variants of cytochrome P450 (CYP). The aim of this
      study was to determine the most suitable mammalian cell line for the in vitro
      drug metabolism analysis of CYP variants. Three reported cell lines (COS-7,
      HepG2, 293T) and one fast-growing variant of the 293 cell line 293FT were
      transfected with vectors expressing green fluorescent protein or typical variants
      of CYP2C9, CYP2C19 or CYP2D6 to investigate the protein expression levels and the
      catalytic activity of expressed CYP allelic variants. The transfected 293FT cells
      had the highest protein expression level and exhibited the highest enzymatic
      activity, while HepG2 cells showed the lowest activity among the four tested cell
      lines. Simultaneously, 293FT cells still maintained the similar relative
      enzymatic ratio among three typical CYP2C9 variants to that of the commonly used
      COS-7 cells. In addition, 293FT cells could also be used for the in vitro
      functional evaluation of two other typical P450 proteins, CYP2C19 and CYP2D6.
      Therefore, the 293FT cell line is more suitable for the in vitro enzymatic
      activity analysis of typical P450 proteins than any other reported mammalian cell
      lines.

PMID- 25975097
TI  - Species differences in the metabolism of ritobegron in vitro and assessment of
      potential interactions with transporters and cytochrome P450 enzymes.
AB  - Ritobegron, a selective beta3-adrenoceptor agonist, is the prodrug of the active
      compound, KUC-7322. We investigated species differences in its metabolism in
      vitro and the potential for drug-drug interactions with ritobegron. In rat, dog,
      monkey, and human liver microsomes, ritobegron was not metabolized by cytochrome
      P450 enzymes (CYPs). KUC-7322 was the only metabolite observed. Hydrolysis of
      ritobegron to KUC-7322 was likely catalyzed by carboxylesterases in human liver
      microsomes. The maximum velocity of the reaction (V(max))/Michaelis-Menten
      constant (K(m)) for hydrolysis of ritobegron to KUC-7322 was much higher in rat
      serum than those in other species. There were also species differences in the
      conjugation of KUC-7322. Sulfate conjugates of ritobegron were detected in all
      species, whereas glucuronide and glutathione conjugates of KUC-7322 were only
      observed in rat liver subcellular fractions. Ritobegron and KUC-7322 did not
      affect the CYP-mediated metabolism of probe substrates in human liver microsomes
      and organic anion transporter 1 (OAT1)-, OAT2-, OAT3-, organic cation transporter
      2 (OCT-2)-, OCT3-, or organic cation/carnitine transporter 1 (OCTN1)-mediated
      uptake of probe substrates in S2 cells. Ritobegron, but not KUC-7322, inhibited P
      glycoprotein-mediated digoxin transport in Caco-2 cells. Significant uptake of
      KUC-7322 was observed in OAT3-expressing S2 cells. Therefore, CYP-mediated drug
      drug interactions are not likely when ritobegron is administered with CYP
      substrates or inhibitors. Ritobegron may increase the plasma concentrations of P
      glycoprotein substrates, such as digoxin, and the plasma concentration of KUC
      7322 may increase when it is administered in combination with OAT inhibitors such
      as probenecid.

PMID- 25975098
TI  - Effects of Polygonum multiflorum on the activity of cytochrome P450 isoforms in
      rats.
AB  - Polygonum multiflorum is a traditional Chinese medicinal herb used in clinical
      medicine to nourish the liver and kidney. However, in recent years, there have
      been increased reports of clinical adverse reactions associated with Polygonum
      multiflorum preparations, especially due to liver injury. The cocktail method can
      be used to assess the influence of Polygonum multiflorum on the activity of
      cytochrome P450 (CYP450) isoforms CYP2B6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, and
      CYP2D6, which were reflected by changes in pharmacokinetic parameters in six
      specific probe drugs: bupropion, omeprazole, tolbutamide, phenacetin, midazolam,
      and metoprolol. Comprised the experimental rats were randomly divided into five
      groups: control group, alcohol extraction A group, alcohol extraction B group,
      water extraction A group, and water extraction B group. Each group five male rats
      and five female rats. Each of the groups received treatments by gavage as
      follows: control group was given normal saline, alcohol extraction A group was
      given 15 g/kg alcohol extract of Polygonum multiflorum (E15), alcohol extraction
      B group was given with 30 g/kg alcohol extract (E30), water extraction A group
      was given 15 g/kg water extract (W15), and water extraction B group was given 30
      g/kg water extract (W30). The extract solution was orally administered once a day
      for 28 consecutive days. The mixture of six probe drugs was given by gavage, and
      blood samples were collected through the tail vein at different time points.
      Probe drug concentration in rat plasma was measured by liquid chromatography-mass
      spectrometry (LC-MS). In the treatment and control groups, Polygonum multiflorum
      alcoholic extract inhibited the activity of CYP2C19 and CYP2C9 and induced the
      activity of CYP1A2. Polygonum multiflorum aquous extract inhibited the activity
      of CYP2B6, CYP2C19, CYP2C9, CYP1A2, and CYP2D6. Pathological sections showed that
      in the alcohol extract group the liver was degenerated inconspicuously, and in
      the water extract group, the cytoplasm had vacuoles and particulate matter. The
      arrangement of liver cells was irregular.

PMID- 25975099
TI  - Methyl gallate from Acer barbinerve decreases melanin synthesis in Mel-Ab cells.
AB  - Methyl gallate (MG) was isolated from the bark of Acer barbinerve, which has
      traditionally been used in Oriental medicine. In the present study, we examined
      the effects of MG on melanin synthesis in Mel-Ab melanocyte cells. MG decreased
      melanin pigmentation in a concentration-dependent manner, but did not directly
      inhibit tyrosinase activity. Further analysis showed that MG had no effect on
      extracellular signal-regulated kinase (ERK) activation, but induced
      phosphorylation of glycogen synthase kinase (GSK)3beta, which is known to
      increase beta-catenin accumulation. Accordingly, the beta-catenin level was
      increased by MG. However, a specific GSK3beta inhibitor did not rescue the MG
      induced inhibition of melanogenesis. Additionally, MG decreased the protein
      expression of microphthalmia-associated transcription factor (MITF) and
      tyrosinase, which regulate melanin synthesis. Based on these results, we conclude
      that MG inhibits melanogenesis by decreasing the expression of MITF and
      tyrosinase.

PMID- 25975100
TI  - The evil of the unknown--risk-benefit evaluation of new synthetic drugs in the
      19th century.
AB  - In the 19th century, synthetic chemistry discovered completely new chemical
      entities for medicinal use, which dramatically enriched the therapeutic
      armamentarium. However, no information was available regarding the safety of
      these new drugs, which were unrelated to most of the medicinal agents formerly
      known. Therefore, the question arises, if and how far, considerations regarding
      the relationship between benefit and risks were made. In this study, chloroform,
      phenazone (antipyrine) and sulfonal, were investigated as examples for drugs
      newly introduced in the 19th century. The results revealed that these drugs were
      provided by the manufacturer, tested by the physicians in a multicentre pattern
      and side effects were published in the medical literature soon after. Within a
      few years, several hundred cases were reported but the data were rarely
      summarized statistically. Therefore, physicians needed to stay updated with the
      medical literature because neither systematic industrial research nor regulatory
      authorities existed. The number of case reports within the first years were
      sufficient to detect common (> 1/100 to < 1/10) side effects but rare events were
      also reported. An extraordinary example is the drug-induced toxic epidermal
      necrolysis, which is commonly known as the Lyell syndrome or its less severe
      form, the Stevens-Johnson syndrome. This reaction has been clearly described by
      Baruch Spitz (1854-1932) as a side effect of antipyrine in 1887, several decades
      before Stevens, Johnson and particularly Lyell.

PMID- 25975101
TI  - [Influence of perfluorodecalin on growth of actinomycetes and intensification of
      Streptomycin and daunorubicin production by the genus Streptomyces kind bacteria
      in submerged culture].
AB  - Addition of perfluorodecalin with gas-transporting function to the liquid medium
      during submerged cultivation of actinomycetes of the genus Streptomyces resulted
      in higher intensity and level of the biomass synthesis and increased production
      of streptomycin and daunorubicin. Addition of perfluorodecalin to the medium
      provided a 2.0-2.3-fold surpass of the maximum antibiotic production (achieved by
      the 120th-144th hours of the culture growth) vs. the antibiotic accumulation
      peaks in the control.

PMID- 25975102
TI  - [Monitoring and antibiotic resistance profile of tracheal aspirate microbiota in
      ICU children with severe craniocerebral trauma].
AB  - Nosocomial infections and their rational antibiotic treatment represent a major
      challenge for the healthcare nowadays. In this context, gramnegative bacteria
      including Pseudomonas aeruginosa, Acinetobacter baumanii and Enterobacteriaceae
      spp. are etiologically important and characterized by a significant level of
      antibiotic resistance. To examine dynamics of the respiratory tract colonization
      by hospital flora, tracheal aspirates obtained at three time points from 69
      children with severe craniocerebral trauma during their stay in ICU were
      analysed. Colonization was observed on the 4th day of the ICU stay with
      predomination of K. pneumoniae (45%) and A. baumanii (27-37%). P. aeruginosa was
      detected after the 8th day of the ICU stay with the isolation rate of 33%.
      Substantial proportions of P. aeruginosa (61%), A. baumanii (78%) and K.
      pneumoniae (25%) were resistant to carbapenems. In 65 carbapemen resistant
      isolates, the presence of carbapenemases was examined using PCRs. OXA-48
      carbapenemase was detected in 11 out of 14 (78%) K. pneumoniae isolates. Among
      the A. baumanii isolates, 30/31 (97%) carried OXA-40 and 1/31 (3%) had OXA-23
      carbapenemases. None of the examined A. baumanii and K. pneumoniae isolates
      produced metallo-betalactamases (MBL). In contrast, all 20 carbapenem resistant
      P. aeruginosa isolates produced a MBL, and in 12 out of 20 (60%) of theme VIM-2
      was detected. Thus, gramnegative nosocomial microflora rapidly colonizes ICU
      patients and has a high level of resistance to antibiotics, including
      carbapenems.

PMID- 25975103
TI  - [Rengalin, a novel drug for treatment of cough in children. Intermediate data on
      multicentre, comparative randomized clinical trial].
AB  - Rengalin liquid formulation on the basis of antibodies to bradikinin histamine
      and morphine was specially designed for the treatment of cough in children. The
      three-component combination in therapeutically active against both dry and wet
      cough due to effect on diverse pathogenetic aspects of the cough reflex. The aim
      of the multicenter, comparative, randomized clinical trial was to estimate the
      efficacy and safety of rengalin in the treatment of cough in patients with acute
      respiratory infection (ARI) of the upper respiratory tract. METHODS: One hundred
      forty six patients at the age of 3 to 17 years (the average age of 8.2 +/- 3.6
      years) from 14 medical centres of Russia were observed. The patients suffered
      from dry/nonproductive, frequent, sore cough preventing from day-time activity
      and/or night sleep (>= 4 by the Cough Severity Scale). The cough duration ranged
      from 12 hours to 3 days. For 3 days the patients of group 1 (n = 71) and group 2
      (n = 75) were treated with rengalin and sinekod (butamirate) respectively. For
      the following 4 days the patients (in case of viscid expectoration were treated
      with ambroxole in the age doses. The results of the Per Protokol Analysis (n = 67
      rengalin group and n = 73 sinekod group) with an account of the Non-Infectiority
      Design are presented. RESULTS: In 3 days the number of the group 1 patients with
      significant improvement/recovery by the day and night estimates amounted to 90%
      and 88% respectively (vs. 81% and 88% in the group 2 patients, no night opisodes
      of cough after 3-days rengalin use being recorded in 52% of the patients vs. 34%
      in the sinekod group patients (p = 0.0003). On the 7th day of the treatment with
      rengalin the number of the children with significant improvement of or recovery
      from day-time cought amounted to 99%and that of the patients with significant
      improvement of or recovery from night-time cough amounted to 93%, in 90% of them
      no night-time cough being recorded (p = 0.0008). As for the patients of the
      reference group, the respective values were 93% and 90%, no night-time cough
      being recorded in 81% of the patients. The time required for development of
      productive/moist cough during the 3-day treatment course in the patients of both
      the group was the same (2.9 +/- 0.3 days in the patients of group 1 and 2.9 +/-
      0.4 days in the group 2 patients. Moreover, in 34% of the rengalin dry cough
      became residual (as rare episode of tussiculation with scantly exudation). After
      3-day course of the rengalin therapy, 66% of the patients was treated with
      ambroxole (versus 95% in sinecod group (p < 0.0001) based on comparative analysis
      and chi2 = 17.7, p > 0.0001 by the results of the frequency analysis). The total
      duration of cough in the patients of groups 1 and 2 was 6.5 +/- 0.8 and 6.7 +/-
      0.7 days respectively (the comparability truth, p = 0.0001). The severity of the
      day-time cough by the area under the curve estimates for 7 days of the treatment
      in the rengalin group patients was equel to 14.3 +/- 5.6 numbers--days and that
      of the patients of the sinekod? group was equal to 15.9?6.1 numbers - days. The
      severity of the night-time cough was equal to 4.2 +/- 2.7 number--days
      respectively. In 2 patients (3%) treated with sinekod signs of ARI generalization
      was observed after the 3-day treatment (p > 0.0001). The research physicians
      investigators (CGI-EL Scale) the combination of the anti- and protussive
      activities in one drug to be efficient and absolutely safe for the chilgren. The
      therapeutic efficacy in the patients of the rengalin group was higher in 3 days
      (2.1 +/- 0.5 numbers) and even in 7 days (2.7 +/- 0.5 numbers). The results value
      in the patients of the sinekod group being 1.8 +/- 0.4 and 2.5 +/- 0.6 numbers
      (one-wayANOVA for repeated estimates ANOVA: Visit - F(1/138) = 146, p < 0.0001,
      TREATMENT--F(1/138) = 9.0, p = 0.003). The factor of the side effects in the
      patients of the rengalin group was zero (no side effects due to the treatment
      were recorded in the patients), whereas in the patients treated with sinekod for
      3 days the respective value was 0.1 +/- 0.3 (true superiority of rengalin by the
      ANOVA data. TREATMENT--F(1/138) = 4.7, p = 0.03). The efficacy factor of the
      rengalin was also in its favour (ANOVA: Visit--F(1/138) = 182, p < 0.0001,
      TREATMENT--F(1y138) = 7.3, p = 0.008). In the patients treated with rengalin
      there were defected no deviations in the biochemical and general clinical
      analyses of blood and urine, no adverse reactions characteristic of antitussive
      drugs of the action. 100-percent adherence to the therapy was stated. CONCLUSION:
      He antitussive effect of rengalin in the treatment of frequent dry day-time and
      night-time cough was observed earlier and proved to be comparable with that of
      butamirate (sinekod). Rengalin prevented significant exudation and viscid
      expectoration in many patients, promoted rapid residual in the patients with dry
      cough and the patients recovery. The use of rengalin for 3 days significantly
      lowered the percentage of the patients requiring treatment with mucolytics at the
      subsequent stages of ARI.

PMID- 25975104
TI  - [Cycloferon therapy of chronic gastroduodenitis in children].
AB  - The efficiency of immunomodulating therapy with cycloferon in children aged from
      10 to 16 years with verified chronic gastroduodenitis was estimated. It was shown
      that the cycloferon treatment provided reliable increase of T- and B-cellular
      populations in mucous membranes of the stomach and duodenum, normalization of the
      number of CD8-lymphocytes, higher titers of IgG antibodies to herpes viruses 1
      and 2. It also promoted reduction of inflammation in the mucous membranes along
      with reduction of the disease clinical signs.

PMID- 25975105
TI  - [Cytoflavin(r) effect on endothelium function and cerebral hemodynamics in
      patients with hypertensive enceplalopathy].
AB  - One hundred forty patients (the average age of 46.7 +/- 7.7 years) with
      hypertensive encephalopathy (HE) were observed. 74 patients of the main group
      received Cytoflavin in a dose of 2 tablets twise a day in the standard basic
      therapy. 66 patients of the reference group received the basic therapy alone. The
      arterial endothelium function was estimated and ultrasonic examination of the
      hemodynamics at five structurally functional levels of the cerebral vascular
      course was used. All the patients with HE had endothelial dysfunction,
      bloodstream depression in the arterial course of the brain vascular system,
      decreased reactivity of the intracranial veins, difficulty in venous outflow. In
      the course of the therapy with Cytoflavin restotation of the arterial endothelial
      function in the patients with HE I stage, the linear and volume speed of
      bloodstream in the main and intracranial cerebral arteries in the patients with
      HE I-II stages, restoration of the intracranial veins reactivity, the linear
      speed of bloodstream in intracranial veins in the patients with all three stages
      of HE, the linear speed of bloodstream in the main veins up to the control values
      in the patients with I-III stages of HE were observed. Interrelation between the
      values of the cerebral hemodynamics and the state of the endothelium function was
      shown.

PMID- 25975106
TI  - [Molecular imprinted polymers for macrolides, aminoglycosides and some other
      biosynthetic antibiotics].
AB  - Molecular imprinted polymers (MIP) for macrolides, aminoglycosides and some other
      biosynthetic antibiotics described in the literature were analysed with a purpose
      of evaluating their possible use for the antibiotics sorption.

PMID- 25975107
TI  - [Antiviral properties of basidiomycetes metabolites].
AB  - The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes,
      Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are
      summurized. The metabolites of these species of basidiomycetes exhibit a direct
      antiviral effect on herpes simplex virus types I and II, human immunodeficiency
      virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus,
      Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased
      antiviral immunity.

PMID- 25975108
TI  - [Induction of type 1, 2 and 3 interferons by acridone acetates].
AB  - The induction profile of endogenous interferons of three types under the action
      of meglumine acridone acetate and sodium acridone acetate, as well as the
      characteristics of the kinetics of their accumulation and circulation in the
      blood of experimental animals are described. Meglumine acridone acetate provided
      balance in induction, production and circulation of the interferons in the blood
      vs. sodium aeridone acetate under the same conditions. The optimal dose of
      meglumine acridone acetate (2.0-3.5 mg/mouse) with effective, consecutive and
      overlapping induction-production of the interferons ensured their prolonged (for
      72 hours) circulation in the blood after a single administration.

PMID- 25975109
TI  - [Persistence of bacteria and viruses in Ixodes].
AB  - Behaviour of viruses and salmonellas in ticks after their single or combined
      contamination was thoroughly studied on laboratory animals with bacteriemia or
      virusemia. When Ixodes ricinus was contaminated simultaneously with forest-spring
      encephalitis virus and salmonellas there were observed a decrease in the virus
      titer by the 30th-40th days and its death in 60 days. In case of the I. ricinus
      nymphs contamination, the virus titer after the combined contamination was by a
      factor of 10(2) lower in 60 days vs. the contamination with the virus alone and
      did not reach the contamination dose. The simultaneous contamination of the ticks
      with two pathogens (forest-spring encephalitis virus and salmonellas) resulted in
      inhibition of the growth and development of both the virus and the salmonellas.

PMID- 25975110
TI  - [Experimental estimation of immunomodulating activity of Tubosan, a new Russian
      synthetic drug].
AB  - Tubosan, a new Russian immunostimulator is a derivative of sulfopyrimidine. It
      stimulated the humoral antiviral immunity in mice, provoked increasing the number
      of the antibody forming cells in the spleen of mice, immunized by sheep's
      erythrocytes, and increased the titers of the virus-neutralizing antibodies after
      immunization by inactivated and live vaccines VEE. The Tubosan ability to lower
      the reactogenicity of the live VEE vaccine provided new perspectives for using
      such immunomodulators in medical practice.

PMID- 25975111
TI  - [Umifenovir (Arbidol) efficacy in experimental mixed viral and bacterial
      pneumonia of mice].
AB  - Pneumonia often occurs as a secondary infection after influenza and accounts for
      a large proportion of the morbidity and mortality associated with seasonal and
      pandemic influenza outbreaks. The efficacy of umifenovir (Arbidol) was
      investigated on a murine model of S. aureus pneumonia following
      A/California/04/2009 (H1N1) influenza virusinfection. Oral treatment with
      umifenovir (40 and 60 mg/kg/day) in all the contamination schemes increased the
      survival rate in the mice from 0% to 90% and lowered the animal weight loss. The
      umifenovir treatment also decreased the virus titer by >= 2 logs and the viable
      bacteria counts in the lungs of the mice. The lungs of the mice treated with
      umifenovir had less severe histopathologic lesions compared to the control group.

PMID- 25975113
TI  - [Study on pharmacokinetics of cefuroxime by dynamics of its distribution in oral
      fluid of patients with sinusitis].
AB  - A method for quantitative determination of cefuroxime in mixed saliva of patients
      with sinusitis by using spectrophotometer Shimadzu UV-1800, combined with the IBM
      PC is described. The conditions of the determination were the following: lambda =
      266 nm, a quartz cuvette, the analysis time of 10 minutes. The method for
      determination of cefuroxime is characterized by high specificity, accuracy, use
      of small amounts of oral fluid and expressivity. The method may be recommended
      for the use in the clinical practice for optimizing cefuroxime therapy in
      patients. The pharmacokinetics of cefuroxime was investigated by the dynamics of
      its distribution in the oral fluid of patients with various infectious-somatic
      disorders.

PMID- 25975112
TI  - [Effect of Hypecoum erectum extract on morphofunctional state of the liver in
      rats with tetracycline-associated hepatitis].
AB  - The effect of Hypecoum erectum L. extract on the morphofunctional condition of
      the liver in rats with experimental tetracycline-associated hepatitis was
      studied. The experiment included 40 albino rats Wistar. The animals treated with
      tetracycline hydrochloride (1.0 g/kg body weight) were exposed to the extract in
      a dose of 50 mg/kg for 5 days. On the 7th day of the experiment the following
      indices were determined: malonic dialdehyde concentration, catalase activity, the
      levels of ATP, pyruvate and lactate in the liver homogenate, as well as the blood
      levels of reduced glutathione. The liver pathomorphological investigation was
      applied. The H. erectum extract was shown to inhibit lipid peroxidation, to
      increase the activity of the host endogenous antioxidant system, to normalize the
      hepatocyte energy provision and to limit the liver degeneration.

PMID- 25975114
TI  - [Antibiotic susceptibility and identification of clinical Pseudomonas fulva
      isolates].
AB  - The earliest eight clinical strains of Pseudomonas fulva were identified in the
      culture collection of pseudomonads isolated in St. Petersburg in 1995-2005, that
      confirmed the medical importance of the species. A high level of the species
      identification of all the strains of P. fulva by MALDI-TOF mass-spectrometry with
      the use of Microflex device with database MALDI Biotyper (Bruker Daltonics Inc.)
      was shown. Tests for routine studies providing identification of P. fulva without
      the use of genetic methods were approved. The profile of the antibiotic
      susceptibility of the clinical strains of P. fulva was described. Acquired
      resistance of two P. fulva isolates to the 3rd generation cephalosporins and
      chloramphenicol was detected.

PMID- 25975115
TI  - [Resistance of clinical strains of pathogenic E. coli to antibiotics and
      bacteriophage in hospitalized children with escherichiosis in St. Petersburg].
AB  - The data on the resistance frequency of the diarrheagenic E. coli isolates to
      antibacterial agents and a specific bacteriophage are presented. The strains were
      isolated from hospitalized children in St. Petersburg in 2011-2013 and belonged
      to three groups, i.e. enteropathogenic (EPE), enterotoxigenic (ETE) and
      enteroinvasine (EIE). It was shown that in the children aged from 1 month to 18
      years the average antibiotic resistance was maximum in the EIE isolates and
      decreased in the following order: EIE (15.2%), EPE (6.0%), ETE (3.3%). The
      clinical EIE isolates showed no resistance to the new generation cephalosporins
      (cefuroxime, cephepime) and nitrofurans. The E. coli isolates of the three groups
      were characterized by high resistance to a specific bacteriophage which decreased
      in the following order: ETE (44.8%), EIE (37.0%), EPE (28.8%). The multiple
      resistance of the diarrheagenic E. coli isolates of the three groups to the
      antibacterials averaged 2.8%. The maximum frequency of resistance of the clinical
      isolates of the three groups to nalidixic acid was observed: EIE - 28.6%, EPE -
      26.3%, ETE - 9.1%. The results of the study may be useful in the tactics of
      therapy of diarrheagenic E. coli infection in children.

PMID- 25975116
TI  - Leadership--more, please.

PMID- 25975117
TI  - Dental students and charity dental care.

PMID- 25975118
TI  - There are some prob1ems that require our immediate attention.

PMID- 25975119
TI  - What is the ARD?
AB  - Until as recently as 100 years ago, the concept of retirement had almost no
      meaning. Now it is a formal stage of life with its own privileges and
      responsibilities We are living longer and learning more about how to take full
      advantage of the opportunities this provides. The Association of Retiring
      Dentists is an organization intended to make that a rich experience for all.

PMID- 25975120
TI  - Every retirement is as personai as every practice.
AB  - Selling a practice is not like selling a car; many lives are bound up in the
      transaction This is a personal narrative about career planning and circumstances.
      Without the author's succession of detailed plans, he never would have been
      sensitive enough to the need for nearly continuous adjustments. In the end, the
      true value of the practice was not measured in dollars.

PMID- 25975121
TI  - Practice transition with intelligence and grace.
AB  - Viable practices change with the professional and personal needs of dentists and
      with trends in society. There is no single way for transitioning out of practice-
      concluding a direct sale, remaining as an associate, and even purchasing a new
      practice to better match one's more mature lifestyle and practiced preferences.
      Changing ratios of dentists to patients currently favor a seller's market and
      emergence of corporate models provide new options. An analysis is given of the
      Canadian practice market. Planning advice is also offered.

PMID- 25975122
TI  - The road back to dental school.
AB  - It is not unusual for dental practice to be book-ended by being a student on the
      front end and a faculty member on the back end, sharing one's accumulated
      experience. Dr. Kenneth Namerow shares his story of trading in his visions of an
      RV after endodontic practice for a second career as an educator.

PMID- 25975123
TI  - Practice transitions--past, present, and future.
AB  - Until the 1960s, the value of a practice upon the retirement of the dentist was
      considered to be nil. In the next several decades, the value of a practice as a
      going business concern was recognized and formulas based on productivity were
      used to establish the sales price of "walkaway" practice transitions.
      Increasingly creative means, such as pre-sale, deferred pre-sale, shareholder
      process, incremental practice sale, and practice mergers have been created to
      make practice transitions more flexible, thereby maximizing the financial value
      of transitions. Dentists at the beginning of their careers will have an
      increasing range of opportunities in the future, with various combinations of
      financial security, freedom from manage- ment concerns, control over the
      practice, and accumulation of equity. Those in the 45- to 55-year age range
      should be planning in detail for their transition. Those older than 55 should
      begin exercising their plans since the future will involve much longer
      transitions.

PMID- 25975124
TI  - There are a lot of ways to go.
AB  - There is much more to transitioning well out of dentistry than maximizing the
      economic value of the practice. The full spectrum of professional and personal
      values, and where each dentist is in his or her life, must be considered. The
      same is true for the staff and the patients, especially for mature family
      oriented practices. A case is worked out in detail, showing that the wisest thing
      to do in some cases is to gradually wind down a practice and stop without selling
      at all.

PMID- 25975125
TI  - An assessment of faculty and dental student decision-making in ethics.
AB  - This study reports and compares dental student and dental faculty scores to
      national norms for the Defining Issues Test 2, a measure of ethical decision
      making competency. The findings showed that dental students and faculty tend to
      make decisions that promote self-interest, paralleling the ethical orientation of
      business professionals. Differences associated with gender, language, and norms
      from previous studies were observed. The findings underscore the importance of
      raising dental faculty and student awareness of their own ethical decision-making
      approaches. More importantly, the findings highlight the need to ensure that
      dental faculty have both the knowledge and skills to train dental students about
      the central role that ethical decision-making must play in patient care.

PMID- 25975126
TI  - Supreme Court ruling may determine the future of state-based professionai
      licensing.
AB  - The U.S. Supreme Court heard oral arguments this fall in a case involving the
      North Carolina State Board of Dental Examiners that could have a dramatic impact
      on how states license and regulate professionals in America. This paper briefly
      describes the facts of the case and the history of professional licensing in
      America and then discuses and evaluates the potential impact of the various legal
      arguments presented by the parties in the case.

PMID- 25975127
TI  - [Analysis of a change in the position of the hyoid bone when displacing the lower
      jaw in patients with dentofacial malformations].
AB  - OBJECTIVE: To estimate the magnitude of a change in the position of the hyoid
      bone when displacing the lower jaw during surgical treatment in patients with
      dentofacial abnormalities. MATERIAL AND METHODS: Fifty patients with dentofacial
      abnormalities (25 and 25 patients with distal and mesial occlusion, respectively)
      were examined and treated. All the patients underwent multislice spiral computed
      tomography before and 6 months after surgery. The authors developed linear
      quantities to analyze the position of the hyoid bone with respect to the skull
      base and cervical spine. The paired Wilcoxon signed-rank test was used. RESULTS:
      None of the examined groups was noted to have a statistically significant change
      in the distance between the basihyoid and the vertebral column, suggesting that
      the datum was moderately changed. No case of worse respiratory function was
      found. CONCLUSION: Our investigation has revealed that mandible displacement
      during orthognathic surgery causes no critcal change in the position of the hyoid
      bone and hence it has no significant impact on upper airway patency in this area.

PMID- 25975128
TI  - [A relationship between cardiac structural and functional parameters, left
      ventricular contractility, and coronary atherosclerosis in patients with type 2
      diabetes mellitus].
AB  - OBJECTIVE: To study the association between echocardiographic (EchoCG) parameters
      in type 2 diabetes mellitus (DM) patients and myocardial contractility and
      coronary angiographic status as evidenced by ventriculography and coronarography.
      MATERIAL AND METHODS: One hundred and thirty-eight patients with morphologically
      verified coronary heart disease (CHD), including 74 patients with verified type 2
      DM in the study group and 64 patients without carbohydrate metabolic disturbances
      in the control group, were examined. All the patients underwent EchoCG and
      coronary angiography with ventriculography. M- and B-mode EchoCG was performed
      using a GE Vivid 4 ultrasound system (USA). RESULTS: The patients with type 2 DM
      concurrent with CHD and decreased left ventricular (LV) contractility showed an
      increase in the number and extent of coronary stenoses and a substantial decrease
      in LV end-diastolic and end-systolic dimensions, LV mass, and LV mass index.
      There were statistically significant correlations between diminished left
      ventricular contractility and main EchoCG parameters. CONCLUSION: The patients
      with type 2 DM concurrent with CHD are more frequently observed to have multiple
      lesions in the coronary arteries (CA), the degree of their stenosis being higher.
      Cardiac structural and functional remodeling in the patients with type 2 DM was
      closely related to CA atherosclerotic changes and decreased myocardial
      contractility.

PMID- 25975129
TI  - [Optimization of a whole-body magnetic resonance imaging protocol for Hodgkin
      lymphoma staging].
AB  - OBJECTIVE: To optimize a whole-body magnetic resonance imaging (WBMRI) protocol
      including diffusion-weighted imaging (DWI) used as a diagnostic complex for
      Hodgkin lymphoma (HL). MATERIAL AND METHODS: The WBMRI protocol adapted for HL
      staging and monitoring was tried out on 1.5 T and 3.0 T MRI scanners. The
      investigation included 128 patients with HL verified by complex clinical,
      laboratory, and instrumental studies (including computed tomography (CT),
      positron emission tomography (PET), PET/CT, scintigraphy and radiology of the
      skeleton, ultrasonography, laboratory tests, and biopsy) and 27 healthy
      individuals. The diagnostic value of the elaborated protocol was determined
      comparing with that of 18F-fluorodeoxyglucose PET, the gold standard for
      diagnosing HL in 63 patients with this condition. RESULTS: WBMRI showed high
      sensitivity (99.2%) (97.6-100% confidence interval (CI)) and specificity (99.6%)
      (99.05-100% CI) in determining the foci of lesion in HL. CONCLUSION: The high
      sensitivity and specificity of WBMRI, which are similar to those of PET, may
      suggest that this method should be used to estimate the extent of the primary
      tumor in HL. Within one study, the proposed non-contrast-enhanced WBMRI protocol
      for 1.5 T and 3.0 T MRI scanners can yield anatomic (T2-WI) and functional (DWI
      estimating the measured diffusion coefficient) MR images of nodal and extra-nodal
      lesions in HL, without increasing time and modernizing equipment and software.
      The proposed protocol improves the quality of HL radiodiagnosis, by concurrently
      reducing a patient's radiation exposure.

PMID- 25975130
TI  - [Results of uterine artery embolization in the treatment of symptomatic uterine
      myoma].
AB  - OBJECTIVE: To evaluate the uterus and myomatous nodules by ultrasonography and
      magnetic resonance imaging in different periods after uterine artery embolization
      (UAE). MATERIAL AND METHODS: UAE was performed in 632 patients with different
      forms of uterine myoma. With this aim in mind, 120 cases with different forms of
      uterine myoma were analyzed. RESULTS: Following 1, 3, 6, and 12 months, the
      reduction in myomatous nodules was estimated to be 18.4 and 17.3, 40.7 and 42.9,
      60.4 and 61.8 and 72.5 and 74.7%, respectively (p < 0.05). Necrotic exposure of a
      nodule, expulsion of myomatous nodules, and removal of a partially nascent
      submucous nodule were observed in 18 (15%) patients. Laparoscopic myomectomy of
      subserous myomatous nodules was carried out in 12 (10%) cases after UAE. In doing
      this, interoperative blood loss was 50-80 ml. CONCLUSION: UAE is an organ
      sparing, highly effective uterine myoma treatment performed alone or in
      combination with surgery in relation to its different forms.

PMID- 25975131
TI  - [Chemoembolization for unresectable colorectal liver metastases with drug-eluting
      microspheres].
AB  - OBJECTIVE: To evaluate the efficiency of chemoembolization using irinotecan
      loaded DC Bead microspheres in the second-line chemotherapy for colorectal liver
      metastases. MATERIAL AND METHODS: In 2008 to 2013, thirty-two patients with
      unresectable colorectal liver metastases underwent 78 chemoembolizations (mean
      2.44 per patient). The results of embolization were assessed by computed
      tomography using the Response Evaluation Criteria in Solid Tumors (RECIST)
      criteria. Survival rates were analyzed applying the Kaplan-Meier method. RESULTS:
      According to the RECIST criteria, a partial response at 3, 6, and 12 months of
      treatment was found in 4, 2, and 0%, respectively. Stabilization was noted in 67,
      53, and 12%. There were no complete responses. The median time to disease
      progression was 225 days; median survival was 420 days. By the study analysis,
      all the patients included in the study died. CONCLUSION: Chemoembolization with
      drug-eluting microspheres may be successfully used in the second-line
      chemotherapy of colorectal liver metastases.

PMID- 25975132
TI  - [Quantitative assessment of the hemodynamic relevance of borderline coronary
      stenoses by myocardial single-photon emission computed tomography with radiation
      absorption correction versus fractional flow reserve].
AB  - OBJECTIVE: To study whether myocardial single-photon emission computed tomography
      (SPECT)/CT with radiation absorption correction (RAC) versus fractional flow
      reserve (FFR) may be used to assess the hemodynamic relevance of borderline
      coronary stenosis in patients with coronary heart disease (CHD). MATERIAL AND
      METHODS: The investigation enrolled 70 patients (50 men and 20 women; mean age 57
      +/- 5 years) diagnosed as having CHD verified by clinical instrumental studies,
      in whom coronary angiography (CA) estimating FFR revealed 50 to 70% coronary
      stenosis; then all the patients underwent SPECT/CT using a two-day rest/exercise
      (bicycle ergometer) protocol; the total injected radiotracer activity was 370-900
      MBq 99mTc-MIBI depending on body weight. RESULTS: A standard 17-segment scheme
      was employed to calculate the SDS index, borderline stenosis detected by CA was
      considered hemodynamically significant at SDS >= 4 in one of the 17 segments,
      which corresponded to one of the major coronary artery, which was compared by the
      authors ith FFR. At SDS >= 4, the sensitivity and specificity of SPECT/CT were
      shown to be 96.7 and 90.6%, respectively. CONCLUSION: Quantitative analysis of
      borderline stenosis by SPECT/CT with RAC increases its specificity and
      sensitivity in estimating the functional significance of borderline coronary
      stenosis.

PMID- 25975133
TI  - [Structured radiology reports].
AB  - The paper reviews the problem of using structured radiology reports. Their
      salient features are as follows: to work out a protocol in accordance with some
      pattern, to divide it into subheadings arranged consecutively and logically and
      broken down by main anatomical structures, types of disease, and study, and to
      use standardized terminology. The RSNA proposed RadLex system is the most known
      example of structured reports. The experience in using these protocols has shown
      that the latter may improve the clearness and informative value of
      roentgenologists' opinions and alleviate their understanding by physicians of
      other specialties. However, the systems of writing the structured radiology
      reports have a number of constraints for the time being, which interfere with
      their wide clinical introduction. Nonetheless, their use is substantially
      increasing in the years ahead.

PMID- 25975135
TI  - [The Russian X-Radiology Research Center: yesterday, today and tomorrow (90 to
      us)].
AB  - The paper gives historical information on the foundation and establishment of the
      Russian X-Radiology Research Center, as well as the advances that have been
      fundamental in the further clinical, scientific, and educational activities of
      the center. It details information of the recent advances of the center in
      diagnosis, including radiation, clinical and molecular gene, and combined
      treatments for cancer patients, including surgery, polychemotherapy, and
      radiotherapy. The achievements of each subdivisions of the Center are given. The
      paper shows the latest advances of the Center and its workers in researches,
      which have been embodied in their dissertations, monographs, and guides. Of great
      importance is the educational process the Center's workers are successfully doing
      in, by training specialists of different profile.

PMID- 25975134
TI  - [Role of positron emission tomography in the hemodynamic evaluation of brain
      tumors].
AB  - The review analyzes the literature on the use positron emission tomography (PET)
      with various radiopharmaceuticals in the assessment of cerebral blood flow,
      perfusion, the blood-brain barrier in order to investigate the biological
      properties, diagnosis, differential diagnosis, staging of brain neoplasms and in
      the evaluation of the efficiency of their treatment. The main qualitative
      perfusion and cerebral blood flow indicators that can be identified by PET are
      described in detail and compared with morphological criteria for estimation of
      angiogenesis and the degree of tumor tissue vascularization.

PMID- 25975137
TI  - [Primary motor cortex as one of the levels of the construction of movements].
AB  - The data obtained during the recent decades led to revision of the dominant in
      neurophysiology view of primary motor cortex as "the cord area" which transfers
      the motor commands to the spinal cord. Contrary to this point of view, it was
      shown that MI primates neurons participate in all stages of organization of motor
      behavior and that the final postures of complex coordinated movements are
      represented in the MI map. Characteristics of movements controlled by MI revealed
      by currently available methods were predicted and explained by N.A. Bernstein
      about 70 years ago. According to his concept, there are some levels of the
      construction of movements that exist in the central nervous system. Area 4 (i.e.
      MI), which is one of them, appeared on the definite stage of evolution for
      resolving the particular movement tasks. In support of this conception we are
      showing that: 1) MI controls the movements that differ from the movements of
      other levels by their characteristics (the mode of operating and the sense
      content); 2) some voluntary movements can be executed without participation of
      MI; 3) different motor areas of the cortex are coupled with different aspects of
      movement behavior.

PMID- 25975136
TI  - [Autism spectrum disorder. Contemporary experimental researches review].
AB  - Autism, like schizophrenia, are heterogeneous diseases, which are directed by
      both genetic factors and external influences in the early stages of development.
      Knowledge about the similarities and differences of these disorders can help
      early diagnosis and treatment. Patients with autism have specific cognitive
      difficulties in social relations. They are characterized by impairment of social
      interaction, communication and behavioral flexibility. The severity of the delay
      the development of autistic children, clinical and psychological indicators is
      correlated with an increase in the high frequency of spontaneous EEG activity.
      Cognitive task in autistic children, unlike normal persons, does not lead to a
      significant restructuring of high-frequency EEG activity, which may be a
      violation of the reaction mechanism to external stimuli and behavioral disorders.
      Abnormality in high-frequency components of EEG reactivity on cognitive task, the
      perception of human faces and visual illusions as well as the inadequate system
      of mirror neurons, can be considered common mechanisms underlying disorders of
      autism and schizophrenia. These general mechanisms may be considered as related
      to violation of the inhibition-exitation balance, controlled via GABA
      transmission and NMDA-receptors. A multidimensional study of patterns of
      disontogenesis in autism, in addition to detailing the clinical picture of
      disease and rehabilitation activities, allows us to clear the fundamental
      understanding of the brain.

PMID- 25975139
TI  - [Dynamic causal modeling of brain electrical responses elicited by simple stimuli
      in visual oddball paradigm].
AB  - Dynamic Causal Modeling (DCM) is a technique designed to assess the effective
      connectivity in the brain, i.e. the influence one neuronal system exerts over
      another. The central idea behind DCM is to treat the brain as a deterministic
      nonlinear dynamical system that is subject to inputs, and produces outputs. DCM
      for EEG uses neural mass model to explain source activity and to build a forward
      model that predicts scalp-recorded response, based on a particular underlying
      network structure. Further analysis is done by selecting, using the Bayesian
      inference, among the competing hypotheses (models) the one that is best to
      explain the data. We used DCM approach to find a plausible model for ERPs
      recorded for standard and deviant stimuli in visual oddball task, and to evaluate
      the reproducibility of this model over a set of individual recordings. The model
      that best explained the data and gave reproducible results was the one that
      allowed the changes in strength of forward connections. These results are
      compatible with the DCM for auditory oddball experiment by other authors.

PMID- 25975138
TI  - [Central EEG rhythm associated with movement and EEG rhythm associated with
      spatial reasoning: are they homologous?].
AB  - EEG rhythmical picture of subject's movement suppression and spatial-figurative
      task solving was examined and analyzed. Rhythms appearing during spatial
      reasoning and suppressed movements with the frequency of about 11 Hz were
      isolated. It was hypothesized that a functional link exists between these rhythms
      in the considered behavioral tests. To test the hypothesis and to reveal this
      connection, experiments were developed and carried out. Then the analysis of
      recorded EEG signals was conducted by applying Fourier transform, independent
      component analysis (ICA) and equivalent dipole source localization. Unexpected
      conclusion about the existence of a general mechanism of movement suppression was
      drawn.

PMID- 25975140
TI  - [The behavior of mice selected for cognitive trait in hyponeophagia test].
AB  - Hungry mice from strain which is under selection for high scores of capacity for
      extrapolation the direction of stimulus movement (line EX) the hyponeophagia
      level (reaction to new food in novel environment) was significantly lower than in
      mice of control unselected population (CoEX). This signify their lower anxiety as
      well as higher neophilia (which in turn is connected to cognitive abilities).
      These mice displayed more:approaches to food, they ate food for longer time
      intervals and their consumed more food. At the same time these mice revealed
      higher anxiety indices in the EPM test controls. The data made it possible to
      suggest that anxiety states which develop in different situations are non
      uniform, and this view finds the confirmation in the literature.

PMID- 25975141
TI  - [Anxiogenic and anxiolytic effects of lithium chloride under preventive and
      therapeutic treatments of male mice with repeated experience of aggression].
AB  - Repeated experience of aggression in daily agonistic interactions is accompanied
      by development of changes in behaviors and psychoemotional states indicating the
      development of the psychopathology of aggressive behavior, which are difficult to
      correct by drugs used for decrease of aggression in the clinics. In this paper
      the influence of lithium chloride on the behavior of aggressive males in
      different tests assessing anxiety, communication and exploratory activity
      (elevated plus maze test, social interaction test, partition test), as well as
      aggressiveness (agonistic interaction test) were studied. Lithium chloride (Sigma
      Aldrich Co, 100 mg/kg/day, i.p.) was administered preventively to male in ranging
      from the 7th day of agonistic interactions, as well as therapeutically to males
      with 21 days of aggression experience during the period without agonistic
      interactions. Also the effects of chronic lithium chloride treatment on behaviors
      of animals without agonistic interactions (intact mice) were studied. Period of
      drug and saline (as the controls) treatment--14 days. It has been shown that
      preventive lithium chloride treatment of male mice with repeated experience of
      aggression induced pronounced anxiogenic effect, under therapeutic treatment-
      nxiolytic effects. Anxiolytic effect was also observed in intact males. There is
      no effect of lithium chloride on aggression. Differences in the effects of
      lithium chloride under preveitive and therapeutic treatments, as well as the
      causes of individual sensitivity to the drug in male mice in one group were
      discussed.

PMID- 25975142
TI  - [Intranasal application of a thyrotropin-releasing hormone attenuates state
      anxiety of the rats].
AB  - During the experiments we investigated the influence of thyrotropin-releasing
      hormone (TRH) on the changes in the behaviour of white rat (Rattus norvegicus)
      males (n = 90), induced by light uncontrolled impact. After two-week procedure of
      handling male rats were tested using elevated plus-maze to determine the basal
      level of anxiety, locomotor and investigative activity and emotionality. A month
      later we investigated the influence of intranasal administration of TRH-solution
      (10(-10) M) in a volume of 20 mkl on the anxiety-level increase, induced by
      stress: short electric foot-shocks. Four hours later animals were tested in the
      elevated plus-maze. In vehicle-treated animals we detected the increase of
      anxiety and emotionality level and the decrease of locomotor and investigative
      activity. In contrast there was no increase of anxiety and emotionality in TRH
      treated rats. As to the locomotor and investigative activity, it decreased in TRH
      treated animals as well as inthe vehicle-treated. It shows the specific influence
      on the level of anxiety, which doesn't affect other components of stress-induced
      behavioral changes Present results suggest TRH as a potential anxiolitic.

PMID- 25975143
TI  - [Age-related changes in behavior, in monoamines and their metabolites content,
      and in density of D1 and D2 dopamine receptors in the brain structures of WAG/Rij
      rats with depression-like pathology].
AB  - Behavior in the light-dark choice, open field, sucrose consumption/preference and
      forced swimming tests, monoamines and their metabolites content in 5 brain
      structures (prefrontal cortex, nucleus accumbens, striatum, hypothalamus,
      hippocampus), and density of D1- and D2-like dopamine receptors in the prefrontal
      cortex, nucleus accumbens and ventral tegmental area were studied in WAG/Rij rats
      at age of 36 days, 3 and 6 months. It has been found that with age, as far as
      spike-wave discharges aggravate, behavioral symptoms of depression (enhanced
      immobility in the forced swimming test, reduced sucrose consumption/preference)
      as well as a hypo-function of the mesolimbic dopaminergic brain system increase
      in WAG/Rij rats. At age of 36 days, when phenotypic expression of absence
      epilepsy in WAG/Rij rats is absent, neurochemical alterations in the brain
      suggesting a hypo-function of the mesolimbic dopaminergic system (deficit of
      dopamine in the nucleus accumbens), as well as symptoms of depression-like
      behavior, are not detected. In WAG/Rij rats, as well as in control rats, density
      of D1-like dopamine receptors in the nucleus accumbens decreased with age. A
      tendency to a lower density of D1-like dopamine receptors was found in WAG/Rij
      rats compared with controls at age of 3 months. In contrast with control rats, in
      WAG/Rij rats, density of D2-like dopamine receptors in the nucleus accumbens
      increased with age. Higher density of D2-like dopamine receptors was observed in
      WAG/Rij rats compared with controls only at age of 6 months when a hypo-function
      of the mesolimbic dopaminergic bran system was extremely pronounced indicating
      that this increase is a compensatory response to a deficit of dopamine.

PMID- 25975144
TI  - [Serotonin and dopamine brain metabolism in mice with different predisposition to
      catalepsy].
AB  - Catalepsy usually is caused by imbalance of dopamine (DA) and serotonin (5-HT)
      systems of brain. The aim of our work was to verify if this imbalance plays an
      important role in the mechanism of hereditary catalepsy in mice. Maintenance of
      DA, 5-HT and their main metabolites--5-hydroxyindoleacetic acid, 3,4
      dihydroxyphenylacetic acid, homovanilic acid was determined in cortex,
      hypothalamus, hippocampus, striatum, substantia nigra and nuclei raphes in
      catalepsy-resistant AKR/J mice strain and catalepsy-prone CBA/LacJ mice strain
      and recombinant mice AKR/J.CBA-D13Mit76 (D13) strain. The latest strain was
      selected by transferring of a fragment of the chromosome 13 from CBA/LacJ
      carrying the main gene of hereditary catalepsy to AKR/J genome. There were no
      interstrain differences in concentration of biogenic amines and their metabolites
      in all brain regions. As a result of our work the hypothesis about the important
      role of 5-HT and/or DA systems of brain in the mechanism of hereditary catalepsy
      in mice was denied.

PMID- 25975145
TI  - [Long-term recording of single unit activity and criteria for estimation of
      stability].
AB  - Stable single-unit recording in the brain of vertebrates allows to investigate
      processes underlying neural plasticity. In applied aspect long-term single-unit
      recording can be useful for development of invasive brain--computer interface.
      Here we propose a criterion for identification of neurons that were recorded for
      more than one day. Based only on the spike forms classification yields ambiguous
      result. Additional parameters (such as form of interspike interval histogram or
      certain parameters of that histogram) decreased misclassification probability
      considerably. Using proposed criterion we were able to identify 82 neurons that
      were recoded for more than one day. In extreme case activity of one neuron was
      observed for 94 days.

PMID- 25975146
TI  - [Application of the method of one-day learning in a Morris water maze to analyse
      the effects of sleep deprivation on memory trace recall 24 hours later, after
      learning].
AB  - The proposed model of a one-day spatial learning is of interest in research of
      how sleep influences the hippocamp-dependent memory consolidation. We have
      studied the influence of a one-day total sleep deprivation on spatial memory
      consolidation in hooded rats after a one-day learning in the Morris water maze
      according to Feldman et al. [2010] protocol. According to it rats had to find a
      submerged platform that was alternatively marked by a flag or completely
      invisible to an animal. In a previous study [Dorokhov et al., 2011] we have used
      another one-day learning protocol [Frick et al., 2000] and Wistar rats and have
      demonstrated a large interindividual variance in learning parameters and sleep
      deprivation effects on memory consolidation. In this study we confirm previously
      acquired results on negative impact of sleep deprivation on spatial memory
      consolidation. To demonstrate the effects of sleep deprivation on the results of
      one-day learning we are using for the first time an evaluation of the time spent
      by an animal in the area of the platform placement and corresponding areas in the
      other quadrants of the water maze.

PMID- 25975147
TI  - [The contagious behavior model on the basis of rat drinking behavior].
AB  - In work, the attempt of contagious behavior modeling on the basis of rat drinking
      behavior was made. Rats' behavior was observed in home cage with two bottles. The
      rat without drinking motivation (viewer) was placed in the cage for adaptation.
      The rat-demonstrator was placed into the same cage 3 minutes later. If the viewer
      was tested with drink-motivated demonstrator, it had less latency of approach to
      bottles, higher frequency of approaches and increased drinking behavior time than
      the rat tested with unmotivated demonstrator or the rat tested without
      demonstrator. The intragastric infusion of coffee increased frequency of
      approaches to demonstrated bottle. Phenazepam intragastric injection decreased
      frequency of approaches and drinking behavior time at demonstrated bottle. The
      results suggest that drugs may affect rat contagious behavior based on drinking
      behavior.

PMID- 25975148
TI  - [Structural and functional organization of centromeres in plant chromosomes].
AB  - The centromere is a specific chromosomal locus that forms the protein complex and
      kinetochore, maintains sister chromatid cohesion, controls chromosome attachment
      to the spindle, and coordinates chromosome movement during mitosis and meiosis.
      Defective centromere assembly or its dysfunction causes cell cycle arrest,
      structural abnormalities of the chromosomes, and aneuploidy. This review collects
      the data on the structure, functions, and epigenetic modification of centromeric
      chromatin, the structure and functions of the kinetochore, and sister chromatid
      cohesion. Taken together, these data provide insight into the specific
      architecture and functioning of the centromere during chromosome division and
      segregation in plants.

PMID- 25975149
TI  - [Genetic variation of the relict species Acanthopanax sessiliflorus (Rupr. et
      Maxim.) Seem. (Araliaceae) in Primorsky Krai].
AB  - Based on the analysis of 17 genes encoding the allozyme diversity of 12 enzyme
      systems, data were obtained on the genetic variation of a relict of the Tertiary
      flora, a valuable medicinal plant Acanthopanax sessiliflorus (Rupr. et Maxim.)
      Seem. (Araliaceae) in the Russian area of its habitat. Indicators of polymorphism
      for populations had rather high values on average (P95 = 42.4%, A = 1.55, H(o) =
      0.211, and H(e) = 0.168), which are comparable with the known data for
      populations of A. sessiliflorus from the peninsula of Korea. The level of genetic
      diversity and its distribution among populations reflects the interaction of
      several factors, among which the most important are the historical past of the
      species, genetic drift, and the plasticity of the reproduction system. The
      obtained data can serve as a basis for the conservation of genetic resources of
      Far Eastern Araliaceae species.

PMID- 25975150
TI  - [Genetic variation at the pantophysin (PanI) locus in North-East Arctic cod Gadus
      morhua L. (Gadiformes: Gadidae) population in the Barents Sea and adjacent
      waters].
AB  - We investigated polymorphisms in the pantophysin gene (Pan I locus) in a
      population of North-East Arctic cod, Gadus morhua L., throughout its foraging
      area in the Barents Sea and adjacent waters. Correlations between the frequencies
      of Pan I alleles and habitat conditions, such as depth and temperature, were
      explored. This study was based on a large number of specimens (2210 individuals)
      of different age and wide geographic sampling coverage. The frequency of the Pan
      I(A) allele, a known genetic marker of coastal cod, varied from zero to 0.47.
      Allele frequencies correlated with depth at the sampling location but not with
      bottom water temperatures. We observed variations in Pan I(A) frequencies among
      different age cohorts from the same area. The most prominent shift in Pan I
      polymorphism was detected at the early stages of the fish life cycle, between
      pelagic juveniles and benthic cod. We found that the Pan I(A) allele frequency in
      pelagic yearling cod was essentially same throughout the studied areas in the
      Barents Sea. In turn, juveniles settling at the northern and deep water locations
      showed a significant decrease in the allele frequency. In contrast, the frequency
      of the Pan I(A) allele remained constant in juveniles settling in shallow waters
      when compared to the pelagic stage. These results confirm the selective nature of
      the cod Pan I locus and indicate that selection process acting on individuals
      with different genotypes at the Pan I locus leads to the formation of a stable
      spatial distribution of allele frequencies observed in adult cod.

PMID- 25975151
TI  - Genetic diversity analysis of eight indigenous goat breeds (groups) in China
      using AFLP markers.
AB  - Eight goat breeds from Chengdu, Lezhi, Jintang, Baiyu, Yingshan, Hejiang,
      Jiangan, and Jialing in Sichuan, China were analyzed for genetic diversity using
      AFLP markers. A total of 261 individuals were analyzed using eight selective AFLP
      primer combinations which generated 174 discernible fragments, of which 80 were
      polymorphic with an average of 27.15 bands per primer pair. Shannon's gene
      diversity index among breeds ranged from 0.0888 to 0.2289, and the highest and
      the lowest gene diversity index among breeds were the Yingshan Black goat
      (0.2289) and the Baiyu Black goat (0.0888) respectively. The genetic distance
      (DR) among eight goat breeds were calculated by Rogers' genetic distance. Based
      on the analytical results, systematic trees were constructed by using the
      unweighted pair-group method with arithmetic average (UPGMA) and the neighbor
      joining (NJ) methods. Eight breeds were divided into two main clusters by using
      cluster analysis, one of which including two subclusters. The clustering results
      agreed well with the origin of the goats and geographic distribution. The results
      implied that AFLP markers were informative and could provide significant insights
      for genetic diversity research and genetic resource conservation of indigenous
      goats.

PMID- 25975152
TI  - [Polymorphisms of bGH, RORC, and DGAT1 genes in Russian beef cattle breeds].
AB  - We examined the allelic and genotypic polymorphisms of genes of the retinoic acid
      receptor-related orphan receptor C (RORC), diacylglycerol acyltransferase-1
      (DGAT1), and growth hormone (bGH) in Russian beef cattle breeds in two
      populations of Kazakh white-headed cattle (of Kazakh and Russian selection) and
      in the Kalmyk cattle breed and Mongolian hogorogo breed, which is related to
      Kalmyk breed. The studied genes are associated with parameters of meat quality:
      marbleness (bGH and RORC) and tenderness (DGAT1). They are also associated with
      an increase in carcass weight (bGH). We found that Russian and Kazakh populations
      of the Kazakh white-headed.breed were characterized by a high content of the AA
      genotype of RORC (0.713 and 0.608, respectively) and of the AA genotype of DGAT1
      (0.913 and 0.975), both of which are preferable for meat quality. The total
      frequencies for the combined genotypes for the bGH and RORC genes, which provide
      for superior meat quality and carcass weight, in the populations of Kazakh white
      headed cattle (GG/AA and GC/AA-68.8% and 57% in the Russian and Kazakh
      populations, respectively) exceeded the frequencies in the two other studied
      breeds by two times. Overall, the obtained results point to the high genetic
      potential of both populations of Kazakh white-headed cattle breeds in beef
      production. Results of this study can be used to improve the selection of meat
      traits in industrial livestock.

PMID- 25975153
TI  - [Association of cytokine gene polymorphisms in peptic ulcer development in the
      Bashkortostan Republic].
AB  - Peptic ulcer disease (PUD) is a chronic disease based on recurrent gastric or
      duodenal ulcers. Association analysis of common polymorphisms of the cytokines
      genes IL1B (rs1143634), IL1RN (rs71941886), IL8 (rs4073), IL10 (rs1800872), and
      TNFA (rs1800629) was conducted in 254 patients with gastric ulcer or duodenal
      ulcer and in 277 unrelated healthy individuals from the Bashkortostan Republic.
      Associations of the rs1143634C allele and the C/C genotype of the IL1B gene with
      PUD in ethnic Bashkirs have been revealed. The frequency of the rs4073A/A
      genotype of the IL8 gene was significantly higher in the control group as
      compared to patients infected with H. pylori. Our results confirm the significant
      role of rs1143634 of the IL1B gene in PUD development.

PMID- 25975154
TI  - [Factors responsible for spatial population genetic Structure in white-spotted
      char Salvelinus leucomaensis (Pallas)].
AB  - Using personal data obtained earlier on the spatial population genetic structure
      of white-spotted char at ten microsatellite loci, an analysis of factors shaping
      the interpopulation divergence was performed. The primary role of genetic drift
      in population differentiation over the distribution range was demonstrated,
      compared to the practically absent role of stepwise mutation process. This result
      points to the common origin and relative connections between southern and
      northern population groups. In the majority of populations, no bottleneck effect
      was detected. Exclusion of the genetically peculiar Primorye population from the
      analysis resulted in the identification of the isolation by distance signatures
      among the examined populations. Such an association can be determined by the
      migratory exchange between the populations, or it could have formed during the
      historical post-Pleistocene colonization of the range.

PMID- 25975155
TI  - [Interspecific polymorphism of the glucosyltransferase domain of the sucrose
      synthase gene in the genus Malus and related species of Rosaceae].
AB  - The sequences that encode the main functional glucosyltransferase domain of
      sucrose synthase genes have been identified for the first time in 14 species of
      the genus Malus and related species of the family Rosaceae, and their
      polymorphism was investigated. Single nucleotide substitutions leading to amino
      acid substitutions in the protein sequence, including the conservative
      transmembrane motif sequence common to all sucrose synthase genes of higher
      plants, were detected in the studied sequences.

PMID- 25975156
TI  - [Defeating the gods of carnage].

PMID- 25975157
TI  - [Involuntary hospitalization and information disclosure obligation].

PMID- 25975158
TI  - [First annual report of the National Suicide Monitoring Center].

PMID- 25975159
TI  - [Diagnosing depression in the adolescent].

PMID- 25975160
TI  - [Traumatic psychological combat disorders. Extraordinary experiences].

PMID- 25975161
TI  - [Clinical approach to post-traumatic stress disorders].
AB  - A confrontation with death can lead to acute reactions of stress, followed
      possibly, after a phase of latency, by post-traumatic stress disorder (PTSD).
      PTSD is characterised by the appearance of a repetition syndrome combining
      reliving, hypervigilance and avoidance; comorbidities frequently arise,
      increasingthe risk of suicide. Caregivers have an important role to play in
      identifying them.

PMID- 25975162
TI  - [Working closely with units to treat war-related psychological trauma].
AB  - French soldiers are carrying out more operational missions than ever and are
      consequently exposed to potentially traumatic events. At the beginning of 2013,
      psychologists were posted to four military medical centres. Working as closely as
      possible to the units, military psychologists can thereby provide early, specific
      and continuous treatment to soldiers with psychological injuries.

PMID- 25975163
TI  - [Rehabilitation and reintegration of soldiers injured on deployment].
AB  - The participation of the French army in the Afghan conflict has highlighted the
      need for discussion and action regarding the pathway, rehabilitation and
      reintegration of soldiers who have been physically or psychologically injured.
      Clinical experience demonstrates that difficulties are less likely to appear
      during the initial treatment phase than later on, when there is less group
      support and there are fewer visible effects of the recognition on the part of the
      institution. It is important to strengthen the links between healthcare personnel
      and institutional players, in order to optimise the medical and social care of
      these war casualties.

PMID- 25975164
TI  - [The "Ecoute Defense" helpline, a new care tool within the military health
      service].
AB  - The "Ecoute Defense" helpline was launched on 23rd January 2013. This freephone
      number, available 24/7, is aimed at soldiers, former soldiers and their families.
      The main objective of the service is to listen, provide information and guide
      those suffering from psychological traumas which have arisen during service.
      Carried out by clinical psychologists from the military health service, the
      mission raises discussion around the challenges of this new channel for accessing
      care for soldiers.

PMID- 25975165
TI  - [Reception and involvement of soldiers' families].
AB  - Faced with a mental health crisis, the intervention of nurses, psychologists and
      psychiatrists is rarely limited to an individual approach. Our team has chosen to
      structure and systematise the involvement of the families of hospitalised
      soldiers.A family psychotherapy consultation has also been reinforced in orderto
      favourthe inclusion of the families of soldiers in crisis. These two tools are
      complementary and have enabled us to enrich the multidisciplinary work within the
      unit, as well as the relationship with the patients and families confronted with
      a crisis.

PMID- 25975166
TI  - [Role of a military psychiatrist in Afghanistan].
AB  - Operational conditions expose soldiers to situations which are potentially
      traumatic on a psychological level. The specific and non specific psychological
      disorders which can result require relatively flexible treatment tools which can
      be adapted to the circumstances.As the first "link in the chain", the
      intervention of a psychiatrist in a theatre of operations enables the
      psychological care to begin at an early stage to be followed by long-term
      treatment when necessary. This article focuses on a mission in Afghanistan.

PMID- 25975167
TI  - [Psychological impact on French soldiers in the Central African Republic].
AB  - The many constraints and psychologically demanding situations to which French
      soldiers are subjected (living conditions, operational pace, scenes of exaction,
      hostile crowds, combat situations) have justified a psychiatrist being posted to
      the theatre of operation Sangaris, in the Central African Republic, soon after
      the military intervention began. While the psychiatrist's activity is typical of
      psychiatry in operational situations,.the configuration of the conflict- a civil
      war - and its impact on the psyche of the soldiers making up the task force have
      resulted in these practices being adapted and acknowledgement of the need to
      update skills.

PMID- 25975168
TI  - [Military psychiatry in a theatre of operations: on mission in Mali].
AB  - The recent missions of military psychiatrists in the theatres of operation
      underline the reactivity of the French healthcare system, focused on the
      expertise of the combat unit doctor. Operation Serval in Mali illustrates in
      particular the methods of medical-psychological support in exceptional
      situations, across a vast geographical area and in very difficult climatic
      conditions. The concept of "forward psychiatry" has a particularly important role
      to play in the early screening and treatment of psychological disorders in order
      to preserve the operational capacity of the deployed personnel.

PMID- 25975169
TI  - [Psychiatry in exceptional situations: the crash of flight AH5017 in Mali].
AB  - The practice of the military psychiatrist comprises different perspectives,
      including a characteristic operational dimension. The unexpected is frequent in
      overseas missions, as illustrated by the crash of the Air Algeria flight in July
      2014 in Mali and the deployment of French forces in the management of this
      disaster.This article reports on the medical-psychological intervention carried
      out in this context.

PMID- 25975170
TI  - [The post-traumatic stress of journalists and war reporters].
AB  - Just like soldiers, war photojournalists, reporters and technicians are subject
      to the risks of being exposed to a traumatic event. While a policy of prevention
      has been implemented within the army, this is not yet really the case with regard
      to press organisations. However, some professionals seek consultations at
      military hospitals. While their symptomatology does not present any notable
      specificities, considerable addictive or depressive comorbidities are observed.
      Managing their care is difficult, particularly as many are reluctant to undertake
      treatment programmes.

PMID- 25975171
TI  - Correlation between subacute sensorimotor deficits and brain water content after
      surgical brain injury in rats.
AB  - Brain edema is a major contributor to poor outcome and reduced quality of life
      after surgical brain injury (SBI). Although SBI pathophysiology is well-known,
      the correlation between cerebral edema and neurological deficits has not been
      thoroughly examined in the rat model of SBI. Thus, the purpose of this study was
      to determine the correlation between brain edema and deficits in standard
      sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague
      Dawley rats were subjected to either sham surgery or surgical brain injury via
      partial frontal lobectomy. All animals were tested for neurological deficits 24
      post-SBI and fourteen were also tested 72 h after surgery using seven common
      behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner
      turn test, forelimb placement test, adhesive removal test, beam balance test, and
      foot fault test. After assessing the functional outcome, animals were euthanized
      for brain water content measurement. Surgical brain injury resulted in
      significantly elevated frontal lobe brain water content 24 and 72 h after surgery
      compared to that of sham animals. In all behavior tests, significance was
      observed between sham and SBI animals. However, a correlation between brain water
      content and functional outcome was observed for all tests except Neuroscore. The
      selection of behavior tests is critical to determine the effectiveness of
      therapeutics. Based on this study's results, we recommend using beam walking, the
      corner turn test, the beam balance test, and the foot fault test since
      correlations with brain water content were observed at both 24 and 72 h post-SBI.

PMID- 25975172
TI  - Challenges of animal models in SCI research: Effects of pre-injury task-specific
      training in adult rats before lesion.
AB  - A rarely explored subject in animal research is the effect of pre-injury
      variables on behavioral outcome post-SCI. Low reporting of such variables may
      underlie some discrepancies in findings between laboratories. Particularly,
      intensive task-specific training before a SCI might be important, considering
      that sports injuries are one of the leading causes of SCI. Thus, individuals with
      SCI often underwent rigorous training before their injuries. In the present
      study, we asked whether training before SCI on a grasping task or a swimming task
      would influence motor recovery in rats. Swim pre-training impaired recovery of
      swimming 2 and 4 weeks post-injury. This result fits with the idea of motor
      learning interference, which posits that learning something new may disrupt
      learning of a new task; in this case, learning strategies to compensate for
      functional loss after SCI. In contrast to swimming, grasp pre-training did not
      influence grasping ability after SCI at any time point. However, grasp pre
      trained rats attempted to grasp more times than untrained rats in the first 4
      weeks post-injury. Also, lesion volume of grasp pre-trained rats was greater than
      that of untrained rats, a finding which may be related to stress or activity. The
      increased participation in rehabilitative training of the pre-trained rats in the
      early weeks post-injury may have potentiated spontaneous plasticity in the spinal
      cord and counteracted the deleterious effect of interference and bigger lesions.
      Thus, our findings suggest that pre-training plays a significant role in recovery
      after CNS damage and needs to be carefully controlled for. 

PMID- 25975173
TI  - Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1
      transgenic mice modeling Alzheimer's disease as well as in wild-type mice.
AB  - Cerebral dopamine neurotrophic factor (CDNF) protects and repairs dopamine
      neurons in animal models of Parkinson's disease, which motivated us to
      investigate its therapeutic effect in an animal model of Alzheimer's disease
      (AD). We employed an established APP/PS1 mouse model of AD and gave
      intrahippocampal injections of CDNF protein or CDNF transgene in an AAV2 viral
      vector to 1-year-old animals. We performed a behavioral test battery 2 weeks
      after the injections and collected tissue samples after the 3-week test period.
      Intrahippocampal CDNF-therapy improved long-term memory in both APP/PS1 mice and
      wild-type controls, but did not affect spontaneous exploration, object neophobia
      or early stages of spatial learning. The memory improvement was not associated
      with decreased brain amyloid load or enhanced hippocampal neurogenesis.
      Intracranial CDNF treatment has beneficial effects on long-term memory and is
      well tolerated. The CDNF molecular mechanisms of action on memory await further
      studies. 

PMID- 25975174
TI  - Behavioral effects and neural changes induced by continuous and not continuous
      treadmill training, post bilateral cerebral ischemia in gerbils.
AB  - This study aims to investigate the effects of treadmill training and the possible
      influences of the start, regularity, and duration after experimental ischemic
      stroke. We performed bilateral occlusion of both the carotid arteries for 5 min
      in Mongolian gerbils. The training groups were: continuous training for 5
      consecutive days or not continuous training for 3 non-consecutive days. The
      groups remained in the treadmill for 15 min, and the training started 12 or 24h
      after the stroke. In the activity cage (AC), behaviors of crossing and distance
      traveled were registered. The forced motor behavior was analyzed by a Rota Rod
      test. After the experiments, the brains were perfused, and coronal sections of
      the striatum, motor cortex M1, and CA1 area of the hippocampus were cut and
      stained with hematoxylin and eosin. Behavioral and morphological data analysis
      was performed by an ANOVA and MANCOVA. Results showed an increased density of
      neurons in the CA1 area of the hippocampus, motor cortex M1, and the striatum in
      ischemic training groups compared to the not training ischemic groups. Animals
      subjected to continuous training that started 24h after ischemia showed a
      satisfactory behavior in the AC and a higher number of striatal neurons when
      compared to ischemic animals. The animals in the not continuous training started
      12h after the stroke showed an unsatisfactory performance in the AC and Rota Rod.
      These findings suggest that early training and not continuous training are
      inadequate for motor behavior improvement after stroke.

PMID- 25975175
TI  - Visual inference of arm movement is constrained by motor representations.
AB  - Several studies support the idea that motion inference is strongly motor
      dependent. In the present study, we address the role of biomechanical constraints
      in motion prediction and how this implicit knowledge can interfere in a spatial
      prediction task. Right-handed (RHS) and left-handed subjects (LHS) had to
      estimate the final position of a horizontal arm movement in which the final part
      of the trajectory was hidden. Our study highlighted a direction effect: end point
      prediction accuracy was better to infer the final position of horizontal motion
      directed toward the median line of human body. This finding suggests that the
      spatial prediction of end point is mapped onto implicit biomechanical knowledge
      such as joint limitation. Accordingly, motor repertoires are embodied into
      spatial prediction tasks. 

PMID- 25975176
TI  - The lack of E318K MITF germline mutation in Latvian melanoma patients.

PMID- 25975177
TI  - Single nucleotide polymorphisms of the NF-kappaB and STAT3 signaling pathway
      genes predict lung cancer prognosis in a Chinese Han population.
AB  - Inflammation contributes to human carcinogenesis and cancer progression. This
      study selected and analyzed single nucleotide polymorphisms (SNPs) of the NF
      kappaB and STAT3 signaling pathway genes for associations with prognosis in 1,165
      lung cancer patients from a Chinese Han population. The data showed that eight
      SNPs (i.e., rs10836, rs3732131, rs3732133, rs4072391, rs2273650, rs1053023,
      rs3744483, and rs28372683) can be grouped into low-, medium-, and high-risk
      genotypes based on survival data. The median overall survival time (MST) of this
      cohort of patients was 24.6 months, whereas the MST of patients with low-risk
      genotypes reached 79.7 months; MST of patients with the medium-risk genotypes was
      25.5 months, and those with high-risk genotypes was 22.7 months. Overall survival
      was statistically different for sex (P = 0.004), age (P = 0.010), histological
      types (P = 0.035), tumor stage (P < 0.001), tumor size (P < 0.001), surgery (P <
      0.001), chemoradiotherapy (P = 0.007), and Karnofsky score (P < 0.001).
      Multivariate analysis and the data from the current study demonstrated that sex,
      tumor stage and size, surgery, chemoradiotherapy, and the aforementioned eight
      SNPs were all independent predictors for overall survival of lung cancer
      patients. 

PMID- 25975178
TI  - Impaired cell envelope resulting from arcA mutation largely accounts for enhanced
      sensitivity to hydrogen peroxide in Shewanella oneidensis.
AB  - Oxidative stress is one of the major challenges that Shewanella encounter
      routinely because they thrive in redox-stratified environments prone to reactive
      oxygen species (ROS) formation, letting alone that ROS can be generated
      endogenously. As respiration is the predominant process for endogenous ROS,
      regulators mediating respiration have been demonstrated and/or implicated to play
      a role in oxidative stress response. In our efforts to unveil the involvement of
      global regulators for respiration in the oxidative stress response, we found that
      loss of the Arc system increases S. oneidensis sensitivity to H2O2 whereas
      neither Fnr nor Crp has a significant role. A comparison of transcriptomic
      profiles of the wild-type and its isogenic arcA mutant revealed that the OxyR
      regulon is independent of the Arc system. We then provided evidence that the
      enhanced H2O2 sensitivity of the arcA mutant is due to an increased H2O2 uptake
      rate, a result of a cell envelope defect. Although one of three proteases of the
      ArcA regulon when in excess is partially accountable for the envelope defect, the
      major contributors remain elusive. Overall, our data indicate that the Arc system
      influences the bacterial cell envelope biosynthesis, a physiological aspect that
      has not been associated with the regulator before. 

PMID- 25975180
TI  - Asymmetric Borane Reduction of Prochiral Ketones Catalyzed By Helical Poly[(S)-3
      vinyl-2,2'-dihydroxy-1,1'-binaphthyl].
AB  - The application of helical poly[(S)-3-vinyl-2,2'-dihydroxy-1, 1'-binaphthyl] (L*)
      in the asymmetric borane reduction of prochiral ketones was studied. The results
      showed that L* had excellent catalytic activity as well as enantioselectivity,
      giving up to 96% yield and up to 99% enantiomeric excess (ee) of the
      corresponding secondary alcohol at 25  degrees C. Moreover, L* can be easily
      recovered and reused without loss of catalytic activity.

PMID- 25975179
TI  - Male-female patient differences in the association between end-of-life
      discussions and receipt of intensive care near death.
AB  - BACKGROUND: Patient gender plays a significant role in patient-physician
      communication, patients' understanding of illness, and the aggressiveness of end
      of-life (EoL) care. However, little is known about the extent to which gender
      differences in the effects of EoL discussions on EoL care contribute to gender
      differences in EoL care. The current study was aimed at determining whether
      gender differences exist in the receipt of intensive care unit (ICU) care near
      death and in the association between EoL discussions and the receipt of EoL ICU
      care. METHODS: This was a multisite, prospective cohort study of patients (n =
      353) with metastatic cancers who were identified as terminally ill at study
      enrollment and were interviewed at a median of 4.1 months before their deaths.
      Postmortem chart reviews and caregiver interviews documented ICU stays in the
      last week of life. RESULTS: Patients who received ICU care at the EoL were more
      likely to be male than those who did not (73% vs 52%, P = .02). After adjustments
      for potential confounders, male patients reporting an EoL discussion were less
      likely to have an ICU stay in the last week of life than male patients with no
      EoL discussion (adjusted odds ratio, 0.26, 95% confidence interval, 0.07-0.91; P
      = .04). There was no association between EoL discussions and ICU stays near death
      among female patients. CONCLUSIONS: Men with advanced cancers are more likely
      than women to receive aggressive, nonbeneficial ICU care near death. Gender
      differences in the effects of EoL discussions on EoL care likely contribute to
      and may even explain gender differences in the receipt of ICU care in the last
      week of life.

PMID- 25975181
TI  - Effect of BioAggregate on Receptor Activator of Nuclear Factor-Kappa B Ligand
      induced Osteoclastogenesis from Murine Macrophage Cell Line In Vitro.
AB  - INTRODUCTION: This study aimed to investigate the effect of BioAggregate, a
      calcium silicate-based nanoparticulate bioceramic, on the regulation of receptor
      activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast
      differentiation and bone resorption in vitro, as well as to delineate the
      underlying molecular mechanism. The performance of BioAggregate was compared with
      that of ProRoot mineral trioxide aggregate (MTA). METHODS: Cells of a murine
      macrophage cell line RAW 264.7 were treated with various concentrations of
      BioAggregate and MTA extracts. Cytotoxicity of material extracts was evaluated
      with Cell Counting Kit-8 assay. RANKL-induced osteoclast differentiation and
      function were assessed with tartrate-resistant acid phosphatase staining, F-actin
      staining, and lacunar resorption pits assay. The mRNA expression associated with
      osteoclast function was detected with quantitative real-time polymerase chain
      reaction. Related molecular signaling pathways were investigated with Western
      blot and immunofluorescence. RESULTS: BioAggregate extracts dose-dependently
      inhibited RANKL-induced osteoclast formation and resorption capacity without
      evident cytotoxicity. RAW 264.7 cells exposed to BioAggregate extracts also
      presented a decrease in RANKL-stimulated mRNA expression of osteoclast-related
      genes and transcription factors. Moreover, cells treated with BioAggregate
      extracts exhibited attenuated TRAF6 expression, suppressed mitogen-activated
      protein kinase signaling, and decreased nuclear translocation of NFATc1 and c-Fos
      in the presence of RANKL. Comparable effects were induced by MTA. CONCLUSIONS:
      BioAggregate and MTA exhibit comparable inhibitory effect on osteoclast
      differentiation and function in vitro, and our findings provide valuable insights
      into the mechanism of bioceramic-mediated anti-osteoclastogenic activity.

PMID- 25975182
TI  - Immunogold labeling reveals subcellular localisation of silica nanoparticles in a
      human blood-brain barrier model.
AB  - Subcellular location of nanoparticles has been widely investigated with
      fluorescence microscopy, via fluorescently labeled antibodies to visualise target
      antigens in cells. However, fluorescence microscopy, such as confocal or live
      cell imaging, has generally limited 3D spatial resolution. Conventional electron
      microscopy can be useful in bridging resolution gap, but still not ideal in
      resolving subcellular organelle identities. Using the pre-embedding immunogold
      electron microscopic imaging, we performed accurate examination of the
      intracellular trafficking and gathered further evidence of transport mechanisms
      of silica nanoparticles across a human in vitro blood-brain barrier model. Our
      approach can effectively immunolocalise a variety of intracellular compartments
      and provide new insights into the uptake and subcellular transport of
      nanoparticles. 

PMID- 25975183
TI  - Traumatic fracture through the neurocentral synchondroses of L3 vertebra in a 5
      year-old child.
AB  - Neurocentral synchondroses (NCS) are growth plates that contribute to the
      transverse growth of the vertebra. Fractures through these NCS are very rare and
      none have been reported in the lumbar spine. We present a rare case of a
      traumatic fracture through the neurocentral synchondroses of L3 vertebra in a 5
      year-old child. 

PMID- 25975184
TI  - Intraosseous migration of tendinous calcifications: cortical erosions,
      subcortical migration and extensive intramedullary diffusion, a SIMS series.
AB  - Calcium hydroxyapatite crystal deposition is a common disorder, which sometimes
      causes acute pain as calcifications dissolve and migrate into adjacent soft
      tissue. Intraosseous calcium penetration has also been described. We illustrate
      the appearance of these lesions using a series of 35 cases compiled by members of
      the French Society of Musculoskeletal Imaging (Societe d'Imagerie Musculo
      Squelettique, SIMS). The first group in our series (7 cases) involved
      calcification-related cortical erosions of the humeral and femoral diaphyses, in
      particular at the pectoralis major and gluteus maximus insertions. A second group
      (28 cases) involved the presence of calcium material in subcortical areas. The
      most common site was the greater tubercle of the humerus, accompanying a
      calcifying tendinopathy of the supraspinatus. In addition, an extensive
      intramedullary diffusion of calcium deposits was observed in four of these cases,
      associated with cortical erosion in one case and subcortical lesions in three
      cases. Cortical erosions and intraosseous migration of calcifications associated
      with calcific tendinitis may be confused with neoplasm or infection. It is
      important to recognize atypical presentations of hydroxyapatite deposition to
      avoid unnecessary investigation or surgery. 

PMID- 25975185
TI  - A new method for measurement of subcoracoid outlet and its relationship to
      rotator cuff pathology at MR arthrography.
AB  - OBJECTIVE: Orthopaedic surgical studies have shown that variations in the
      vertical distance between the tip of the coracoid process and the supra-glenoid
      tubercle alter the shape of the subcoracoid outlet. Our objective was to measure
      the vertical distance between the coracoid tip and the supra-glenoid tubercle
      (CTGT) on MR and to assess whether this showed better correlation with rotator
      cuff pathology compared with the axial coraco-humeral distance. MATERIALS AND
      METHODS: A retrospective review was performed of 100 consecutive shoulder MR
      arthrograms. Vertical distance between the coracoid tip and the supraglenoid
      tubercle was measured in the sagittal oblique plane. Separate assessment was then
      made of tendon pathology of the subscapularis, supraspinatus and long head of
      biceps tendons. Axial coraco-humeral distance was then measured. Correlation
      between tendon abnormalities and the two measurements was then made. RESULTS: Of
      the 100 cases, 42 had subscapularis tendon lesions, 21 had lesions of the long
      head of biceps and 53 had supraspinatus tendon lesions. Mean vertical distance
      from the coracoid tip to supraglenoid tubercle was greater in those with lesions
      of any of these tendons and was statistically significant for the supraspinatus
      group (P = 0.005). Reduced axial coraco-humeral distance was also seen in
      patients with tendinopathy, although with less statistically significant
      difference (p = 0.059). CONCLUSION: Our results support orthopaedic studies that
      have shown that the vertical distance between the coracoid tip and the
      supraglenoid tubercle increases the incidence and risk of rotator cuff disease by
      altering the shape of the subcoracoid outlet.

PMID- 25975186
TI  - Erratum to: Disruption of the proximal tibiofibular joint in the setting of multi
      ligament knee injury.

PMID- 25975187
TI  - Secondary metabolites from Ganoderma.
AB  - Ganoderma is a genus of medicinal mushrooms. This review deals with secondary
      metabolites isolated from Ganoderma and their biological significance.
      Phytochemical studies over the last 40years led to the isolation of 431 secondary
      metabolites from various Ganoderma species. The major secondary compounds
      isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes,
      alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic
      acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes
      (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones
      (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l)
      prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o)
      benzenoid derivatives. Ganoderma lucidum is the species extensively studied for
      its secondary metabolites and biological activities. Ganoderma applanatum,
      Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae,
      Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma
      hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum,
      Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum,
      Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma
      theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the
      other Ganoderma species subjected to phytochemical studies. Further phytochemical
      studies on Ganoderma could lead to the discovery of hitherto unknown biologically
      active secondary metabolites. 

PMID- 25975188
TI  - Ischemic Colitis After Routine Colonoscopy.

PMID- 25975189
TI  - Comprehensive analysis of factors impacting risks and outcomes of therapy-related
      myeloid neoplasms following breast cancer treatment.

PMID- 25975190
TI  - Adverse prognostic impact of KIT mutations in childhood CBF-AML: the results of
      the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial.

PMID- 25975193
TI  - [Not Available].

PMID- 25975191
TI  - Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic
      acid improves the efficacy of daratumumab.
AB  - Daratumumab is an anti-CD38 monoclonal antibody with lytic activity against
      multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular
      cytotoxicity) and CDC (complement-dependent cytotoxicity). Owing to a marked
      heterogeneity of response to daratumumab therapy in MM, we investigated
      determinants of the sensitivity of MM cells toward daratumumab-mediated ADCC and
      CDC. In bone marrow samples from 144 MM patients, we observed no difference in
      daratumumab-mediated lysis between newly diagnosed or relapsed/refractory
      patients. However, we discovered, next to an expected effect of effector (natural
      killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant
      association between CD38 expression and daratumumab-mediated ADCC (127 patients),
      as well as CDC (56 patients). Similarly, experiments with isogenic MM cell lines
      expressing different levels of CD38 revealed that the level of CD38 expression is
      an important determinant of daratumumab-mediated ADCC and CDC. Importantly, all
      trans retinoic acid (ATRA) increased CD38 expression levels but also reduced
      expression of the complement-inhibitory proteins CD55 and CD59 in both cell lines
      and primary MM samples. This resulted in a significant enhancement of the
      activity of daratumumab in vitro and in a humanized MM mouse model as well. Our
      results provide the preclinical rationale for further evaluation of daratumumab
      combined with ATRA in MM patients. 

PMID- 25975192
TI  - Wideband arrhythmia-Insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping
      without image artifacts induced by an implantable-cardioverter-defibrillator.
AB  - PURPOSE: To develop and evaluate a wideband arrhythmia-insensitive-rapid (AIR)
      pulse sequence for cardiac T1 mapping without image artifacts induced by
      implantable-cardioverter-defibrillator (ICD). METHODS: We developed a wideband
      AIR pulse sequence by incorporating a saturation pulse with wide frequency
      bandwidth (8.9 kHz) to achieve uniform T1 weighting in the heart with ICD. We
      tested the performance of original and "wideband" AIR cardiac T1 mapping pulse
      sequences in phantom and human experiments at 1.5 Tesla. RESULTS: In five
      phantoms representing native myocardium and blood and postcontrast blood/tissue
      T1 values, compared with the control T1 values measured with an inversion
      recovery pulse sequence without ICD, T1 values measured with original AIR with
      ICD were considerably lower (absolute percent error > 29%), whereas T1 values
      measured with wideband AIR with ICD were similar (absolute percent error < 5%).
      Similarly, in 11 human subjects, compared with the control T1 values measured
      with original AIR without ICD, T1 measured with original AIR with ICD was
      significantly lower (absolute percent error > 10.1%), whereas T1 measured with
      wideband AIR with ICD was similar (absolute percent error < 2.0%). CONCLUSION:
      This study demonstrates the feasibility of a wideband pulse sequence for cardiac
      T1 mapping without significant image artifacts induced by ICD.

PMID- 25975194
TI  - Nurses' characteristics and organisational factors associated with their
      assessments of individualised care in care institutions for older people.
AB  - RATIONALE: Individualised care is considered a key attribute of the quality in
      clinical care. Despite the environment in which the care is delivered and the
      care providers can influence in this concept, perceptions of individuality in the
      care settings for older people are rarely studied. AIM: To identify nurses'
      characteristics and organisational factors associated with nurses' views about
      the provision of individualised care in care settings for older people. STUDY
      DESIGN: A cross-sectional multisite survey design. METHODS: A multisite survey of
      nursing staff (N = 1513, n = 874, response rate 58%) working in 62 different
      units for older people in southwest Finland was carried out using self
      administered questionnaires (The Individualised Care Scale-Nurse-B and a
      questionnaire gathering socio-demographic and organisational variables). Data
      were analysed using descriptive statistics, Spearman's correlation coefficients,
      paired-sample t-tests and one-way analyses of variance. RESULTS: Participants'
      perceptions about the level of individualised care provided to older people were
      generally positive (Mean 3.92, SD 0.56). In this regard, taking into account the
      patients' clinical situation (Mean 4.31, SD 0.53) and the support of older
      patients' decisional control (Mean 3.80, SD 0.71) obtained the highest scores.
      Regarding nurses' socio-demographic variables, a positive correlation between age
      and type of organisation with the assessments of individualised care provision
      was found. CONCLUSIONS: The findings of this study show that nurses' age and the
      type of organisation where the care is delivered have an impact on the
      perceptions of individualised care of nurses working in institutions for older
      people. The participants' assessments about individualised care delivery have
      practical utility as it may help managers better understand and develop areas
      that obtained the lowest scores. This information may lead to the reduction of
      barriers (structures and processes) that hinder individualised care delivery and
      facilitate programs aimed at developing professional environments that improve
      the delivery of older people's care.

PMID- 25975195
TI  - Systematic review and meta-analysis of phase I/II targeted therapy combined with
      radiotherapy in patients with glioblastoma multiforme: quality of report,
      toxicity, and survival.
AB  - To perform a systematic review and meta-analysis of severe adverse events (SAE)
      reported in early trials combining molecularly targeted therapies (MTT) with
      radiotherapy (RT), and to compare them to standard therapy. A summary data meta
      analysis was performed and compared to the historical standard. Inclusion
      criteria were phase I and/or II trials published between 2000 and 2011, with
      glioblastoma multiforme patients treated with RT and MTT. Pooled incidence rates
      (IR) of SAE were estimated as well as the pooled median progression-free survival
      (PFS) and overall survival (OS). Nineteen prospective trials (9 phase I, 1 phase
      I/II and 9 phase II) out of 29 initially selected were included (n = 755
      patients). The exact number of patients who had experienced SAE was mentioned in
      37 % of the trials, concerning only 17 % of the patients. Information such as the
      period during which adverse events were monitored, the planned treatment
      duration, and late toxicity were not reported in the trials. The pooled IR of
      overall SAE was 131.2 (95 % CI 88.8-193.7) per 1000 person-months compared to
      74.7 (63.6-87.8) for standard therapy (p < 0.01). Significant differences were
      observed for gastrointestinal events (p = 0.05) and treatment-related deaths (p =
      0.02), in favour of standard therapy. No significant difference was observed in
      PFS and OS. Reporting a summary of toxicity data in early clinical trials should
      be stringently standardized. The use of MTT with RT compared to standard therapy
      increased SAE while yielded comparable survival in glioblastoma multiforme
      patients.

PMID- 25975196
TI  - Skin imaging modalities quantify progression and stage of infantile haemangiomas.

PMID- 25975197
TI  - Crassulacean acid metabolism: a continuous or discrete trait?
AB  - The key components of crassulacean acid metabolism (CAM) - nocturnal fixation of
      atmospheric CO2 and its processing via Rubisco in the subsequent light period -
      are now reasonably well understood in terms of the biochemical reactions defining
      this water-saving mode of carbon assimilation. Phenotypically, however, the
      degree to which plants engage in the CAM cycle relative to regular C3
      photosynthesis is highly variable. Depending upon species, ontogeny and
      environment, the contribution of nocturnal CO2 fixation to 24-h carbon gain can
      range continuously from close to 0% to 100%. Nevertheless, not all possible
      combinations of light and dark CO2 fixation appear equally common. Large-scale
      surveys of carbon-isotope ratios typically show a strongly bimodal frequency
      distribution, with relatively few intermediate values. Recent research has
      revealed that many species capable of low-level CAM activity are nested within
      the peak of C3 -type isotope signatures. While questions remain concerning the
      adaptive significance of dark CO2 fixation in such species, plants with low-level
      CAM should prove valuable models for investigating the discrete changes in
      genetic architecture and gene expression that have enabled the evolutionary
      transition from C3 to CAM.

PMID- 25975198
TI  - Prevalence of classic, MLB-clade and VA-clade Astroviruses in Kenya and The
      Gambia.
AB  - BACKGROUND: Infectious diarrhea leads to significant mortality in children, with
      40 % of these deaths occurring in Africa. Classic human astroviruses are a well
      established etiology of diarrhea. In recent years, seven novel astroviruses have
      been discovered (MLB1, MLB2, MLB3, VA1/HMO-C, VA2/HMO-B, VA3/HMO-A, VA4);
      however, there have been few studies on their prevalence or potential association
      with diarrhea. METHODS: To investigate the prevalence and diversity of these
      classic and recently described astroviruses in a pediatric population, a case
      control study was performed. Nine hundred and forty nine stools were previously
      collected from cases of moderate-to-severe diarrhea and matched controls of
      patients less than 5 years of age in Kenya and The Gambia. RT-PCR screening was
      performed using pan-astrovirus primers. RESULTS: Astroviruses were present in 9.9
      % of all stool samples. MLB3 was the most common astrovirus with a prevalence of
      2.6 %. Two subtypes of MLB3 were detected that varied based on location in
      Africa. In this case-control study, Astrovirus MLB1 was associated with diarrhea
      in Kenya, whereas Astrovirus MLB3 was associated with the control state in The
      Gambia. Classic human astrovirus was not associated with diarrhea in this study.
      Unexpectedly, astroviruses with high similarity to Canine Astrovirus and Avian
      Nephritis Virus 1 and 2 were also found in one case of diarrhea and two control
      stools respectively. CONCLUSIONS: Astroviruses including novel MLB- and VA-clade
      members are commonly found in pediatric stools in Kenya and The Gambia. The most
      recently discovered astrovirus, MLB3, was the most prevalent and was found more
      commonly in control stools in The Gambia, while astrovirus MLB1 was associated
      with diarrhea in Kenya. Furthermore, a distinct subtype of MLB3 was noted, as
      well as 3 unanticipated avian or canine astroviruses in the human stool samples.
      As a result of a broadly reactive PCR screen for astroviruses, new insight was
      gained regarding the epidemiology of astroviruses in Africa, where a large
      proportion of diarrheal morbidity and mortality occur.

PMID- 25975199
TI  - Sequence and expression variations suggest an adaptive role for the DA1-like gene
      family in the evolution of soybeans.
AB  - BACKGROUND: The DA1 gene family is plant-specific and Arabidopsis DA1 regulates
      seed and organ size, but the functions in soybeans are unknown. The cultivated
      soybean (Glycine max) is believed to be domesticated from the annual wild
      soybeans (Glycine soja). To evaluate whether DA1-like genes were involved in the
      evolution of soybeans, we compared variation at both sequence and expression
      levels of DA1-like genes from G. max (GmaDA1) and G. soja (GsoDA1). RESULTS:
      Sequence identities were extremely high between the orthologous pairs between
      soybeans, while the paralogous copies in a soybean species showed a relatively
      high divergence. Moreover, the expression variation of DA1-like paralogous genes
      in soybean was much greater than the orthologous gene pairs between the wild and
      cultivated soybeans during development and challenging abiotic stresses such as
      salinity. We further found that overexpressing GsoDA1 genes did not affect seed
      size. Nevertheless, overexpressing them reduced transgenic Arabidopsis seed
      germination sensitivity to salt stress. Moreover, most of these genes could
      improve salt tolerance of the transgenic Arabidopsis plants, corroborated by a
      detection of expression variation of several key genes in the salt-tolerance
      pathways. CONCLUSIONS: Our work suggested that expression diversification of DA1
      like genes is functionally associated with adaptive radiation of soybeans,
      reinforcing that the plant-specific DA1 gene family might have contributed to the
      successful adaption to complex environments and radiation of the plants.

PMID- 25975200
TI  - Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases
      Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue.
AB  - BACKGROUND: Mitochondrial dysfunction in adipose tissue has been implicated as a
      pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose
      tissue, chronic nutrient overload results in mitochondria driven increased
      reactive oxygen species (ROS) leading to carbonylation of proteins that impair
      mitochondrial function and downregulation of key genes linked to mitochondrial
      biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads
      to improvements in glycemic profile prior to significant weight loss.
      Consequently, we hypothesized that improved glycemia early after RYGB would be
      paralleled by decreased protein carbonylation and increased expression of genes
      related to mitochondrial biogenesis in adipose tissue. METHODS: To evaluate this
      hypothesis, 16 obese individuals were studied before and 7-8 days following RYGB
      and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained
      pre- and post-bariatric surgery as well as from eight healthy, non-obese
      individual controls. RESULTS: Prior to surgery, adipose tissue expression of
      PGC1alpha, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower
      expression in the obese bariatric surgery group when compared to lean controls (p
      < 0.05). Following RYGB, but not after AGB, patients showed significant decrease
      in HOMA-IR, reduction in adipose protein carbonylation, and increased expression
      of genes linked to mitochondrial biogenesis. CONCLUSIONS: These results suggest
      that rapid reduction in protein carbonylation and increased mitochondrial
      biogenesis may explain postoperative metabolic improvements following RYGB.

PMID- 25975201
TI  - Roux-en-Y Gastric Bypass Surgery in Patients with Polycystic Ovary Syndrome and
      Metabolic Syndrome.
AB  - BACKGROUND: We aimed to evaluate the impact of Roux-en-Y gastric bypass (RYGB)
      surgery on metabolic syndrome-related variables in obese women with polycystic
      ovarian syndrome (PCOS). METHODS: Thirteen obese women with PCOS (Rotterdam
      criteria) who met the International Diabetes Federation criteria for metabolic
      syndrome and who qualified for RYGB were enrolled. Clinical examinations included
      ovarian ultrasonography and measurement of waist, hip, body mass index and blood
      pressure. Venous blood samples were taken at the visit before surgery to measure
      triglyceride, high-density lipoprotein, low-density lipoprotein, fasting glucose,
      glycated haemoglobin (HbA1c), serum progesterone, allopregnanolone, total
      testosterone and sex hormone-binding globulin (SHBG) levels. Six months after
      surgery, patients underwent the same examinations and provided blood samples to
      analyse the same variables. RESULTS: At 6 months after surgery, the metabolic
      syndrome-related variables improved in all patients, except in six patients with
      anovulatory menstrual cycles who still satisfied the criteria for metabolic
      syndrome. The metabolic variables normalised and serum progesterone and
      allopregnanolone levels increased in seven patients with ovulatory cycles.
      Testosterone and SHBG normalised in all patients at 6 months after surgery. Serum
      HDL and diastolic blood pressure did not change after surgery. Correlations were
      found among testosterone, progesterone, allopregnanolone, lipoproteins,
      triglyceride, fasting glucose and HbA1c levels, which was interpreted as
      progesterone and its metabolite allopregnanolone may contribute to metabolic
      abnormalities. CONCLUSIONS: In PCOS patients, normalisation of metabolic
      dysfunction may be incomplete by 6 months after RYGB surgery, and the start of
      ovulatory menstrual cycles may indicate normalisation of metabolic dysfunction.

PMID- 25975202
TI  - Decreased expression of ARID1A associates with poor prognosis and promotes
      metastases of hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy worldwide,
      which is especially prevalent in Asia. Elucidating the molecular basis of HCC is
      crucial to develop targeted diagnostic tools and novel therapies. Recent studies
      have identified AT-rich interactive domain-containing protein 1A (ARID1A) as a
      broad-spectrum tumor suppressor. We evaluated the clinical implications of
      decreased ARID1A expression in HCC, and investigated the mechanisms of ARID1A
      mediated tumor suppression. METHODS: Quantitative PCR, western blotting,
      immunohistochemical analysis of ARID1A mRNA and protein expression was conducted
      in 64 paired HCC and adjacent non-tumorous tissues. ARID1A function was evaluated
      in vitro in MHCC-97H and Huh7 HCC cell lines, and in vivo in a xenografted HCC
      tumor model. RESULTS: ARID1A mRNA and protein expression were significantly
      decreased in HCC tissues, and decreased expression was significantly associated
      with overall metastasis, including local lymph node and distant metastasis, and
      poor prognosis. ARID1A knockdown promoted HCC cell migration and invasion in
      vitro, whereas overexpression of ARID1A inhibited migration and invasion. E
      cadherin levels were closely correlated with ARID1A expression, suggesting a role
      in migration and invasion. In addition, ARID1A and E-cadherin (CDH1) expression
      were found to be regulated in a coordinated fashion in HCC samples. Furthermore,
      ARID1A knockdown significantly increased HCC tumor growth and lung metastasis in
      vivo. CONCLUSIONS: ARID1A served as an important tumor suppressor. Decreased
      expression of ARID1A was associated with tumor progression, metastasis, and
      reduced overall survival in mice and humans. ARID1A could represent a promising
      candidate therapeutic target for HCC.

PMID- 25975203
TI  - A critical role of striatal A2A R-mGlu5 R interactions in modulating the
      psychomotor and drug-seeking effects of methamphetamine.
AB  - Addiction to psychostimulants is a major public health problem with no available
      treatment. Adenosine A2A receptors (A2A R) co-localize with metabotropic
      glutamate 5 receptors (mGlu5 R) in the striatum and functionally interact to
      modulate behaviours induced by addictive substances, such as alcohol. Using
      genetic and pharmacological antagonism of A2A R in mice, we investigated whether
      A2A R-mGlu5 R interaction can regulate the locomotor, stereotypic and drug
      seeking effect of methamphetamine and cocaine, two drugs that exhibit distinct
      mechanism of action. Genetic deletion of A2A R, as well as combined
      administration of sub-threshold doses of the selective A2A R antagonist (SCH
      58261, 0.01 mg/kg, i.p.) with the mGlu5 R antagonist, 3-((2-methyl-4
      thiazolyl)ethynyl)pyridine (0.01 mg/kg, i.p.), prevented methamphetamine- but not
      cocaine-induced hyperactivity and stereotypic rearing behaviour. This drug
      combination also prevented methamphetamine-rewarding effects in a conditioned
      place preference paradigm. Moreover, mGlu5 R binding was reduced in the nucleus
      accumbens core of A2A R knockout (KO) mice supporting an interaction between
      these receptors in a brain region crucial in mediating addiction processes.
      Chronic methamphetamine, but not cocaine administration, resulted in a
      significant increase in striatal mGlu5 R binding in wild-type mice, which was
      absent in the A2A R KO mice. These data are in support of a critical role of
      striatal A2A R-mGlu5 R functional interaction in mediating the ambulatory,
      stereotypic and reinforcing effects of methamphetamine but not cocaine-induced
      hyperlocomotion or stereotypy. The present study highlights a distinct and
      selective mechanistic role for this receptor interaction in regulating
      methamphetamine-induced behaviours and suggests that combined antagonism of A2A R
      and mGlu5 R may represent a novel therapy for methamphetamine addiction.

PMID- 25975204
TI  - Vascular endothelial growth factor affects dendritic cell activity in
      hypertensive disorders of pregnancy.
AB  - Vascular endothelial growth factor (VEGF) activity is involved in the growth and
      stability of the placenta, and its signaling has been implicated in the
      development of pregnancy-induced hypertension (PIH). The present study sought to
      evaluate VEGF levels and dendritic cell (DC) profiles in patients with PIH, and
      to investigate the effects of VEGF expression on DC phenotypes. The present study
      assessed 162 patients, 112 of whom were diagnosed with PIH. Serum VEGF was
      measured by ELISA, while myeloid DC (mDC; (Lin1-HLA-DR+CD11c+) and plasmacytoid
      DC (pDC; Lin1-HLA-DR+CD123+) counts were determined using flow cytometry. In
      order to determine the effect of VEGF treatment on DC phenotypes, immature DCs
      (iDCs) were separated from monocytes by culturing in the presence of cytokines
      (GM-CSF, IL-4), and then pretreated with VEGF or lipopolysaccharide (LPS). The
      phenotype of dendritic cells (CD14, CD80, CD83, or CD86) was determined by flow
      cytometry. The levels of VEGF in the serum of patients with PIH were
      significantly lower than those in control subjects (P<0.05). The percentage of
      pDCs found in the serum of patients with preeclampsia was significantly lower
      than that in the other groups. The percentage of mDCs in the serum of patients
      with preeclampsia and eclampsia was significantly higher than that in the control
      and hypertensive disorder groups (P<0.05). The percentage of mDCs was
      significantly negatively correlated with the levels of VEGF in the preeclamptic
      and eclamptic patients (r=-0.34 and r=-0.42, respectively; P<0.05). Detected
      levels of CD80, CD83 and CD86 in DCs treated with VEGF were significant lower
      than those in DCs treated with LPS alone (P<0.05). In conclusion, abnormal
      expression of VEGF and an altered dendritic cell profile may be involved in the
      development of PIH.

PMID- 25975206
TI  - Rethinking biogeographic patterns: high local variation in relation to
      latitudinal clines for a widely distributed species.
AB  - Wide-ranging species typically differ morphologically across their ranges.
      Bergmann's rule suggests that taxa in colder environments are bigger than related
      taxa in warmer locations. We examined 767 painted turtles (Chrysemys picta) in
      ten populations near their northwestern range edge in south-central British
      Columbia, Canada, in conjunction with previous data, to test the hypotheses of
      (1) a Bergmann's latitudinal cline, and (2) that males and females show similar
      latitudinal variation in size. We also explicitly test the impact of high local
      variation on range-wide inference. Female and male turtles showed similar
      latitudinal clines in body size; the degree of sexual dimorphism did not change
      across the range. Importantly, local variation in sexual dimorphism across ponds
      was nearly as high as the previously observed continental variation. Indeed, we
      found both the lowest and the highest degrees of sexual size dimorphism that have
      ever been reported for this species. Further, differing criteria in the
      literature for identifying mature females compound the difficulty of interpreting
      latitudinal clines in size or dimorphism. Our results highlight the need for much
      more systematic local and regional sampling as inputs for latitudinal or other
      comparative analyses such as Rensch's rule because insufficient sampling of high
      local variation may mask important ecological and evolutionary patterns. 

PMID- 25975205
TI  - Effects of anticoagulation on markers of activation of clotting following major
      orthopedic surgery.
AB  - INTRODUCTION: This study examines makers of activation of clotting following
      three chemoprophylactic regimens used for prevention of postoperative venous
      thromboembolic disease (TED) following high-risk surgery for TED. METHODS:
      Patients having elective primary knee or hip replacement surgery received
      variable dose warfarin (target international normalized ratios 2.0-2.5), 1 mg
      warfarin daily starting 7 days preoperatively or aspirin 325 mg daily starting on
      the day of surgery. Twelve patients in each group were treated for 28 +/- 2 days.
      Thrombin-antithrombin (T-AT) and prothrombin fragment F1 + 2 were measured at
      baseline and postoperative days 3 and 28 +/- 2. RESULTS: Thrombin-antithrombin
      and F1 + 2 on postoperative day 3 were equal for the study groups. By days 28 +/-
      2, variable dose warfarin therapy group suppressed production of F1 + 2 (P =
      0.002) with no difference in the T-AT accumulation. F1 + 2 for other patients
      overlapped the normal range. CONCLUSION: The signals of activated clotting
      following surgery did not differentiate the three regimens on postoperative day
      3. Variable dose warfarin was associated with suppression of F1 + 2 after 1 month
      of therapy, with no effect on accumulation of T-AT. Fixed low-dose warfarin
      started 7 days prior to surgery and aspirin are not inferior on postoperative day
      3, but appear to be inferior over a longer treatment.

PMID- 25975207
TI  - Femoral diameter and stem type are independent risk factors for ARMD in the large
      headed ASR THR group.
AB  - BACKGROUND: Adverse soft-tissue reaction to metal debris (ARMD) continues to be
      major source of concern in metal-on-metal (MoM) hip replacements. In our earlier
      study we were able to establish several risk factors for ARMD in patients who had
      received a small-diameter (<50 mm) Articular Surface Replacement (ASR, DePuy,
      Warsaw, IN, USA). The aims of the present study were to analyze whether these
      previously established risk factors also apply to patients who have received a
      large-headed (>50 mm) ASRTM XL THR. METHODS: Large-headed ASR total hip
      replacements were used in 225 operations (196 patients) at our institution. 176
      patients (203 hips) attended a screening programme, consisting of a clinical
      evaluation, whole blood cobalt and chromium measurements, and cross-sectional
      imaging. RESULTS: Revision surgery was performed on 84 hips (37%) in 75 patients.
      ARMD was diagnosed in the majority (n = 73 [87%]) of these revisions. Cumulative
      8-year survivorship was 52%. The previously established risk factors for ARMD
      were not applicable. Interestingly, increasing femoral diameter and stem type
      were identified as independent risk factors for ARMD but reduced cup coverage had
      no significant association with ARMD. CONCLUSIONS: Stem type and increasing
      femoral size as independent risk factors for ARMD in the cohort of ASR XL THR
      patients, support the importance of taper failure in the development of ARMD. The
      present results suggest that the degree of taper failure may be variable and
      dependent on the taper design.

PMID- 25975208
TI  - Assessing the quality of published genetic association studies in meta-analyses:
      the quality of genetic studies (Q-Genie) tool.
AB  - BACKGROUND: Advances in genomics technology have led to a dramatic increase in
      the number of published genetic association studies. Systematic reviews and meta
      analyses are a common method of synthesizing findings and providing reliable
      estimates of the effect of a genetic variant on a trait of interest. However,
      summary estimates are subject to bias due to the varying methodological quality
      of individual studies. We embarked on an effort to develop and evaluate a tool
      that assesses the quality of published genetic association studies. Performance
      characteristics (i.e. validity, reliability, and item discrimination) were
      evaluated using a sample of thirty studies randomly selected from a previously
      conducted systematic review. RESULTS: The tool demonstrates excellent
      psychometric properties and generates a quality score for each study with
      corresponding ratings of 'low', 'moderate', or 'high' quality. We applied our
      tool to a published systematic review to exclude studies of low quality, and
      found a decrease in heterogeneity and an increase in precision of summary
      estimates. CONCLUSION: This tool can be used in systematic reviews to inform the
      selection of studies for inclusion, to conduct sensitivity analyses, and to
      perform meta-regressions.

PMID- 25975209
TI  - Examining the Factor Structure and Structural Invariance of the PANAS Across
      Children, Adolescents, and Young Adults.
AB  - It is unclear what factor structure best represents the Positive and Negative
      Affect Schedule (PANAS) from childhood to adulthood. The PANAS structure was
      examined in a sample of 555 children (M age = 11.66, SD = 1.24), 608 adolescents
      (M age = 15.45, SD = 1.09), and 553 young adults (M age = 18.75, SD = 1.00). A
      partially invariant model consisting of Positive Affect, Fear, and Distress
      factors best represented the PANAS across all age groups, indicating that the
      underlying constructs are the same across age but that the factors become
      increasingly interrelated with increasing age. 

PMID- 25975210
TI  - Whole body MRI, including diffusion-weighted imaging in follow-up of patients
      with testicular cancer.
AB  - BACKGROUND: Whole body (WB) magnetic resonance imaging (MRI), including diffusion
      weighted imaging (DWI) has become increasingly utilized in cancer imaging, yet
      the clinical utility of these techniques in follow-up of testicular cancer
      patients has not been evaluated. The purpose of this study was to evaluate the
      feasibility of WB MRI with continuous table movement (CTM) technique, including
      multistep DWI in follow-up of patients with testicular cancer. PATIENTS AND
      METHODS: WB MRI including DWI was performed in follow-up of 71 consecutive
      patients (median age, 37 years; range 19-84) with histologically confirmed
      testicular cancer. WB MRI protocol included axial T1-Dixon and T2-BLADE sequences
      using CTM technique. Furthermore, multi-step DWI was performed using b-value 50
      and 1000 s/mm(2). One criterion for feasibility was patient tolerance and
      satisfactory image quality. Another criterion was the accuracy in detection of
      any pathological mass, compared to standard of reference. Signal intensity in DWI
      was used for evaluation of residual mass activity. Clinical, laboratory and
      imaging follow-up were applied as standard of reference for the evaluation of WB
      MRI. RESULTS: WB MRI was tolerated in nearly all patients (69/71 patients, 97%)
      and the image quality was satisfactory. Metal artifacts deteriorated the image
      quality in six patients, but it did not influence the overall results. No case of
      clinical relapse was observed during the follow-up time. There was a good
      agreement between conventional WB MRI and standard of reference in all patients.
      Three patients showed residual masses and DWI signal was not restricted in these
      patients. Furthermore, DWI showed abnormally high signal intensity in a normal
      sized retroperitoneal lymph node indicating metastasis. The subsequent (18)F-FDG
      PET/CT could verify the finding. CONCLUSION: WB MRI with CTM technique including
      multi-step DWI is feasible in follow-up of patients with testicular cancer. DWI
      may contribute to important added-value data to conventional MRI sequences
      regarding the activity of residual masses.

PMID- 25975211
TI  - Lymphoma grading with FDG-PET/CT readdressed: Direct and timely histopathological
      correlation study.

PMID- 25975212
TI  - Testing the Invariance of the National Health and Nutrition Examination Survey's
      Sexual Behavior Questionnaire Across Gender, Ethnicity/Race, and Generation.
AB  - Federal and state policies are based on data from surveys that examine sexual
      related cognitions and behaviors through self-reports of attitudes and actions.
      No study has yet examined their factorial invariance--specifically, whether the
      relationship between items assessing sexual behavior and their underlying
      construct differ depending on gender, ethnicity/race, or age. This study examined
      the factor structure of four items from the sexual behavior questionnaire part of
      the National Health and Nutrition Examination Survey (NHANES). As NHANES provided
      different versions of the survey per gender, invariance was tested across gender
      to determine whether subsequent tests across ethnicity/race and generation could
      be done across gender. Items were not invariant across gender groups so data
      files for women and men were not collapsed. Across ethnicity/race for both
      genders, and across generation for women, items were configurally invariant, and
      exhibited metric invariance across Latino/Latina and Black participants for both
      genders. Across generation for men, the configural invariance model could not be
      identified so the baseline models were examined. The four item one factor model
      fit well for the Millennial and GenerationX groups but was a poor fit for the
      baby boomer and silent generation groups, suggesting that gender moderated the
      invariance across generation. Thus, comparisons between ethnic/racial and
      generational groups should not be made between the genders or even within gender.
      Findings highlight the need for programs and interventions that promote a more
      inclusive definition of "having had sex."

PMID- 25975213
TI  - Preferences for Masculinity Across Faces, Bodies, and Personality Traits in
      Homosexual and Bisexual Chinese Men: Relationship to Sexual Self-Labels and
      Attitudes Toward Masculinity.
AB  - This study examined preferences for masculinity across faces, bodies, and
      personality traits in 462 homosexual and bisexual men in China. The impact of
      sexual self-labels (tops, bottoms, and versatiles) and attitude toward male
      masculinity on preferences for masculinity were also examined. Participants were
      asked to select the seven most desirable personality traits for a romantic
      partner from a list of 32 traits of gender roles. A series of 10 masculinized and
      feminized dimorphic images of male faces and bodies were then presented to
      participants, who were required to identify their preferred image. The results
      indicated that participants preferred more masculine faces, bodies, and
      personality traits. Significant differences in preferences for masculinity were
      found between tops, bottoms, and versatiles, with both bottoms and versatiles
      preferring more masculine faces, bodies, and personality traits than did tops. In
      addition, preferences for masculinity across faces, bodies, and traits showed a
      significant positive correlation with each other for all sexual self-labels,
      indicating a consistent preference for masculinity. Attitude toward male
      masculinity was significantly correlated with facial, body, and trait
      preferences; individuals with more rigid attitudes toward male masculinity (low
      acceptance of femininity in males) preferred more masculine characters. These
      results indicate a consistent preference for masculinity between both physical
      features (faces and bodies) and personality traits (instrumentality) that may be
      affected by observer perception.

PMID- 25975214
TI  - Introduction to the Special Section on DSM-5: Classifying Sex.

PMID- 25975215
TI  - The influence of deformation height on estimating the center of pressure during
      level and cross-slope walking on sand.
AB  - Force plates are frequently used to collect the ground reaction forces (GRF) and
      center of pressure (COP) during gait. The calculated COP is affected by the
      material type and thickness covering the top surface. If the surface is
      deformable, these effects can be significant. The purpose of this study is to
      simulate and evaluate the effects of deformation height when calculating the COP
      in a deformable surface during gait. The GRF and COP data during normal gait were
      collected from 20 healthy adult males on sand in two conditions (level and cross
      slope of 10 degrees ). The COP differences in the anteroposterior (AP) and
      mediolateral (ML) directions were modeled for constant deformation heights (10-50
      mm, 10 mm increments). The results showed the magnitude of COP changes in the AP
      and ML directions were different in both level and cross-slope conditions. A
      significantly larger COPML difference was shown for the cross-slope condition
      than level condition for the same deformation height. The COP was more sensitive
      to the deformation height for the downhill limb than uphill limb in the cross
      slope condition. The results of this study suggest that the maximum allowable
      deformation height before a correction for surface deformation is needed is 20mm
      for level condition and 10mm for cross-slope condition, where 3mm difference in
      COP is considered as the tolerance limit. Surface deformations beyond these
      thresholds may lead to an inaccurate interpretation and evaluation of joint
      kinetics during gait on deformable surfaces.

PMID- 25975216
TI  - Cellular response of chondrocytes to magnesium alloys for orthopedic
      applications.
AB  - In the present study, the effects of Mg-Nd-Zn-Zr (JDBM), brushite (CaHPO4.2H2O)
      coated JDBM (C-JDBM), AZ31, WE43, pure magnesium (Mg) and Ti alloy (TC4) on
      rabbit chondrocytes were investigated in vitro. Adhesion experiments revealed the
      satisfactory morphology of chondrocytes on the surface of all samples. An
      indirect cytotoxicity test using MTT assay revealed that C-JDBM and TC4 exhibited
      results similar to those of the negative control, better than those obtained with
      JDBM, AZ31, WE43 and pure Mg (p<0.05). There were no statistically significant
      differences observed between the JDBM, AZ31, WE43 and pure Mg group (p>0.05). The
      results of indirect cell cytotoxicity and proliferation assays, as well as those
      of apoptosis assay, glycosaminoglycan (GAG) quantification, assessment of
      collagen II (Col II) levels and RT-qPCR revealed a similar a trend as was
      observed with MTT assay. These findings suggested that the JDBM alloy was highly
      biocompatible with chondrocytes in vitro, yielding results similar to those of
      AZ31, WE43 and pure Mg. Furthermore, CaHPO4.2H2O coating significantly improved
      the biocompatibility of this alloy.

PMID- 25975217
TI  - Taming a wild beast: Developing molecular tools and new methods to understand the
      biology of Zymoseptoria tritici.
AB  - Septoria blotch of wheat is one of the world's most serious plant diseases, which
      is difficult to control due to the absence of durable host resistance and the
      increasing frequency of fungicide-resistance. The ascomycete fungus that causes
      the disease, Zymoseptoria tritici, has been very challenging to study. This
      special issue of Fungal Genetics and Biology showcases an integrated approach to
      method development and the innovation of new molecular tools to study the biology
      of Z. tritici. When considered together, these new methods will have a rapid and
      dramatic effect on our ability to combat this significant disease. 

PMID- 25975218
TI  - When is facial diplegia regarded as a variant of Guillain-Barre syndrome?
AB  - A variant of Guillain-Barre syndrome (GBS) with predominant manifestation of
      facial diplegia (FD) has been described recently. This study aimed to
      characterize and determine the incidence of this FD-predominant GBS variant. The
      clinical and serological information of 900 consecutive patients were reviewed.
      In total, eight patients were identified between January 2007 and December 2010
      as having FD accompanied by some features of GBS. These features were subjective
      sensory symptoms such as distal paresthesia (7/8, 88%), albumin-cytological (A/C)
      dissociation (7/8, 88%), antecedent infection (6/8, 75%), and minor nerve
      conduction study (NCS) abnormalities (5/7, 71%). One patient presented with the
      typical NCS feature of demyelinating neuropathy. Only two patients exhibited
      areflexia (2/8, 25%). None of the patients possessed any anti-ganglioside
      antibodies; however, the serum of two patients was positive for anti-mycoplasma
      antibody (2/6, 33%). FD variant of GBS occurred in less than 1% of our dataset.
      FD can be a regional variant of GBS when it is accompanied by supporting
      features, such as subjective tingling, A/C dissociation, and minor NCS
      abnormalities. 

PMID- 25975219
TI  - Stac gets the skeletal L-type calcium channel unstuck.
AB  - Commentary to: Stac adaptor proteins regulate trafficking and function of muscle
      and neuronal L-type Ca2+ channels. (Proc. Natl. Acad. Sci. 2015, pp. 602-606).

PMID- 25975220
TI  - Water and other fluids in nephrolithiasis: State of the art and future
      challenges.
AB  - Adequate hydration, as to maintain urinary volume over 2 L/day, has long been
      considered as the cornerstone medical prescription for preventing
      nephrolithiasis. However, scientific evidence about what kind of water stone
      formers should drink and about the effects of other beverages on urinary stone
      risk factors is sometimes unclear. Moreover, the recommendation that water
      therapy prevents kidney stone recurrence relies on only one randomized controlled
      trial, even if more epidemiologic and basic science studies seem to support this
      assumption. Therefore, in this review we analyze current evidence that support
      water therapy in nephrolithiasis and we highlight the possible effects of
      different types of water and other beverages on lithogenic risk, giving some
      practical recommendations for what stone formers should be advised to prevent
      recurrence.

PMID- 25975221
TI  - De-escalation: A survey of clinical staff in a secure mental health inpatient
      service.
AB  - De-escalation is an important tool for preventing aggression in inpatient
      settings but definitions vary and there is no clear practice guideline. We aimed
      to identify how clinical staff define and conceptualize de-escalation, which de
      escalation interventions they would use in aggressive scenarios, and their
      beliefs about the efficacy of de-escalation interventions. A questionnaire survey
      (n = 72) was conducted using open and closed questions; additionally, clinical
      vignettes describing conflict events were presented for participants to describe
      their likely clinical response. Qualitative data were subject to thematic
      analysis. The major themes that de-escalation encompassed were communication,
      tactics, de-escalator qualities, assessment and risk, getting help, and
      containment measures. Different types of aggression were met with different
      interventions. Half of participants erroneously identified p.r.n. medication as a
      de-escalation intervention, and 15% wrongly stated that seclusion, restraint, and
      emergency i.m. medication could be de-escalation interventions. Those
      interventions seen as most effective were the most commonly used. Clinical
      staff's views about de-escalation, and their de-escalation practice, may differ
      from optimal practice. Use of containment measures and p.r.n. medication where de
      escalation is more appropriate could have a negative impact; work is needed to
      promote understanding and use of appropriate de-escalation interventions based on
      a clear guideline.

PMID- 25975223
TI  - Public must be made aware of need for research in children, report says.

PMID- 25975222
TI  - Phosphate binder pill burden, patient-reported non-adherence, and mineral bone
      disorder markers: Findings from the DOPPS.
AB  - Because of multiple comorbidities, hemodialysis (HD) patients are prescribed many
      oral medications, including phosphate binders (PBs), often resulting in a high
      "pill burden." Using data from the international Dialysis Outcomes and Practice
      Patterns Study (DOPPS), we assessed associations between PB pill burden, patient
      reported PB non-adherence, and levels of serum phosphorus (SPhos) and parathyroid
      hormone (PTH) using standard regression analyses. The study included data
      collected from 5262 HD patients from dialysis units participating in the DOPPS in
      12 countries. PB prescription ranged from a mean of 7.4 pills per day in the
      United States to 3.9 pills per day in France. About half of the patients were
      prescribed at least 6 PB pills per day, and 13% were prescribed at least 12 PB
      pills per day. Overall, the proportion of patients who reported skipping PBs at
      least once in the past month was 45% overall, ranging from 33% in Belgium to 57%
      in the United States. There was a trend toward greater PB non-adherence and a
      higher number of prescribed PB pills per day. Non-adherence to PB prescription
      was associated with high SPhos (>5.5 mg/dL) and PTH (>600 pg/mL). Adherence to PB
      is a challenge for many HD patients and may be related to the number of PB pills
      prescribed. Prescription of a simplified PB regimen could improve patient
      adherence and perhaps improve SPhos and PTH levels. 

PMID- 25975224
TI  - The VEGFR2, COX-2 and MMP-2 polymorphisms are associated with clinical outcome of
      patients with inoperable non-small cell lung cancer.
AB  - Certain common inherited variations in genes involved in tumor angiogenesis,
      progression and metastasis may contribute to cancer therapy outcome and prognosis
      by altering the gene expression and protein activity. In this report, we examined
      the effect of functional polymorphisms in MMP-1, MMP-2, MMP-3, VEGF, VEGFR2,
      FGFR4 and COX-2 genes on overall (OS) and progression-free survival (PFS) of 350
      Caucasian patients with inoperable non-small cell lung cancer (NSCLC). The
      results of multivariate analysis indicated that VEGFR2 -906C and COX-2 -1195G
      alleles were strongly associated with poor OS and PFS (p = 0.002 and 0.015,
      respectively, for OS; p = 0.009 and 0.015, respectively, for PFS), while MMP-2 
      1306 T allele carriers had significantly reduced PFS (p = 0.010). Moreover, an
      increased risk of death and progression was significantly associated with the
      number of adverse alleles for VEGFR2/COX-2 (p = 0.0005 for OS and 0.0006 for PFS
      in >1 adverse allele carriers) and VEGFR2/COX-2/MMP-2 combinations (p = 0.0003
      for OS and 0.0001 for PFS in patients with >2 adverse alleles). Finally, VEGFR2
      TC/CC, COX-2 AG/GG and MMP-2 CT/TT genotypes as well as "at risk" allele
      combinations were identified as independent predictors of unfavorable OS and PFS
      in the group. In conclusion, the data suggest that selected VEGFR2, COX-2 and MMP
      2 polymorphisms may be potential prognostic markers in unresectable NSCLC treated
      with radiotherapy with or without chemotherapy, although further validation
      studies are warranted to confirm our observations.

PMID- 25975225
TI  - C-Raf deficiency leads to hearing loss and increased noise susceptibility.
AB  - The family of RAF kinases transduces extracellular information to the nucleus,
      and their activation is crucial for cellular regulation on many levels, ranging
      from embryonic development to carcinogenesis. B-RAF and C-RAF modulate
      neurogenesis and neuritogenesis during chicken inner ear development. C-RAF
      deficiency in humans is associated with deafness in the rare genetic insulin-like
      growth factor 1 (IGF-1), Noonan and Leopard syndromes. In this study, we show
      that RAF kinases are expressed in the developing inner ear and in adult mouse
      cochlea. A homozygous C-Raf deletion in mice caused profound deafness with no
      evident cellular aberrations except for a remarkable reduction of the K(+)
      channel Kir4.1 expression, a trait that suffices as a cause of deafness. To
      explore the role of C-Raf in cellular protection and repair, heterozygous C-Raf
      (+/-) mice were exposed to noise. A reduced C-RAF level negatively affected
      hearing preservation in response to noise through mechanisms involving the
      activation of JNK and an exacerbated apoptotic response. Taken together, these
      results strongly support a role for C-RAF in hearing protection. 

PMID- 25975227
TI  - FDA-approved small-molecule kinase inhibitors.
AB  - Kinases have emerged as one of the most intensively pursued targets in current
      pharmacological research, especially for cancer, due to their critical roles in
      cellular signaling. To date, the US FDA has approved 28 small-molecule kinase
      inhibitors, half of which were approved in the past 3 years. While the clinical
      data of these approved molecules are widely presented and structure-activity
      relationship (SAR) has been reported for individual molecules, an updated review
      that analyzes all approved molecules and summarizes current achievements and
      trends in the field has yet to be found. Here we present all approved small
      molecule kinase inhibitors with an emphasis on binding mechanism and structural
      features, summarize current challenges, and discuss future directions in this
      field. 

PMID- 25975228
TI  - Report calls for $2bn global fund to kickstart antibiotic development.

PMID- 25975226
TI  - Apaf1-deficient cortical neurons exhibit defects in axonal outgrowth.
AB  - The establishment of neuronal polarity and axonal outgrowth are key processes
      affecting neuronal migration and synapse formation, their impairment likely
      leading to cognitive deficits. Here we have found that the apoptotic protease
      activating factor 1 (Apaf1), apart from its canonical role in apoptosis, plays an
      additional function in cortical neurons, where its deficiency specifically
      impairs axonal growth. Given the central role played by centrosomes and
      microtubules in the polarized extension of the axon, our data suggest that Apaf1
      deletion affects axonal outgrowth through an impairment of centrosome
      organization. In line with this, centrosomal protein expression, as well as their
      centrosomal localization proved to be altered upon Apaf1-deletion. Strikingly, we
      also found that Apaf1-loss affects trans-Golgi components and leads to a robust
      activation of AMP-dependent protein kinase (AMPK), this confirming the stressful
      conditions induced by Apaf1-deficiency. Since AMPK hyper-phosphorylation is known
      to impair a proper axon elongation, our finding contributes to explain the effect
      of Apaf1-deficiency on axogenesis. We also discovered that the signaling pathways
      mediating axonal growth and involving glycogen synthase kinase-3beta, liver
      kinase B1, and collapsing-response mediator protein-2 are altered in Apaf1-KO
      neurons. Overall, our results reveal a novel non-apoptotic role for Apaf1 in
      axonal outgrowth, suggesting that the neuronal phenotype due to Apaf1-deletion
      could not only be fully ascribed to apoptosis inhibition, but might also be the
      result of defects in axogenesis. The discovery of new molecules involved in
      axonal elongation has a clinical relevance since it might help to explain
      neurological abnormalities occurring during early brain development.

PMID- 25975230
TI  - Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused
      by a Novel R782G Mutation in CSF1R.
AB  - We report a new family with autosomal dominant inheritance of a late onset
      rapidly progressive leukodystrophy in which exome sequencing has revealed a novel
      mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R).
      Neuropathology of two affected family members showed cerebral white matter
      degeneration with axonal swellings and pigmented macrophages. The few recently
      reported families with CSF1R mutations had been previously labelled "hereditary
      diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary
      orthochromatic leukodystrophy" (POLD), disorders which now appear to form a
      disease continuum. The term "adult-onset leukoencephalopathy with axonal
      spheroids and pigmented glia" (ALSP) has been proposed to encompass this
      spectrum. As CSF1R regulates microglia this mutation implies that dysregulation
      of microglia is the primary cause of the disease. 

PMID- 25975229
TI  - The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje
      mouse model of Down syndrome.
AB  - Human fetuses with Down syndrome demonstrate abnormal brain growth and reduced
      neurogenesis. Despite the prenatal onset of the phenotype, most therapeutic
      trials have been conducted in adults. Here, we present evidence for fetal brain
      molecular and neonatal behavioral alterations in the Ts1Cje mouse model of Down
      syndrome. Embryonic day 15.5 brain hemisphere RNA from Ts1Cje embryos (n = 5) and
      wild type littermates (n = 5) was processed and hybridized to mouse gene 1.0 ST
      arrays. Bioinformatic analyses were implemented to identify differential gene and
      pathway regulation during Ts1Cje fetal brain development. In separate
      experiments, the Fox scale, ultrasonic vocalization and homing tests were used to
      investigate behavioral deficits in Ts1Cje pups (n = 29) versus WT littermates (n
      = 64) at postnatal days 3-21. Ts1Cje fetal brains displayed more differentially
      regulated genes (n = 71) than adult (n = 31) when compared to their age-matched
      euploid brains. Ts1Cje embryonic brains showed up-regulation of cell cycle
      markers and down-regulation of the solute-carrier amino acid transporters.
      Several cellular processes were dysregulated at both stages, including apoptosis,
      inflammation, Jak/Stat signaling, G-protein signaling, and oxidoreductase
      activity. In addition, early behavioral deficits in surface righting, cliff
      aversion, negative geotaxis, forelimb grasp, ultrasonic vocalization, and the
      homing tests were observed. The Ts1Cje mouse model exhibits abnormal gene
      expression during fetal brain development, and significant neonatal behavioral
      deficits in the pre-weaning period. In combination with human studies, this
      suggests that the Down syndrome phenotype manifests prenatally and provides a
      rationale for prenatal therapy to improve perinatal brain development and
      postnatal neurocognition.

PMID- 25975231
TI  - The use of dynamic thermal analysis to distinguish between genuine and
      counterfeit drugs.
AB  - WHO estimates that 10% of drugs are falsified. Economic and health factors
      arising from the use of counterfeit drugs lead to the development of new methods
      for distinguishing genuine medicines from falsified ones. The purpose of this
      study was to develop a new, fast, and inexpensive method to distinguish between
      original and fake drugs. 10 counterfeit Viagra((r)) tablets were compared to 4
      original pills (Pfizer). The drugs - both original and fake - were heated to 60
      degrees C and then the dynamics of their temperature changes at ambient
      conditions was tested using a thermal imaging camera. The time constants tau
      showing the dynamics of temperature changes for Viagra((r)) and the falsified
      drug were determined. The thermokinetic parameters of drugs were determined in
      the temperature range of 60-22.2 degrees C. Both original and counterfeit tablets
      had different time constants: 171.44 +/- 4.62s and 182.71 +/- 4.05 s,
      respectively. Differences in the dynamics of temperature changes as a function of
      time are particularly pronounced in the range of t+2 to t+7 min. The comparison
      of the time constants tau enables to distinguish between genuine and counterfeit
      drugs. The proposed new method which uses dynamic thermal analysis is an
      effective, cheap and fast technique to distinguish genuine drugs from counterfeit
      ones.

PMID- 25975232
TI  - Interactions of short-acting, intermediate-acting and pre-mixed human insulins
      with free radicals--Comparative EPR examination.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was used to examine insulins
      interactions with free radicals. Human recombinant DNA insulins of three groups
      were studied: short-acting insulin (Insuman Rapid); intermediate-acting insulins
      (Humulin N, Insuman Basal), and pre-mixed insulins (Humulin M3, Gensulin M50,
      Gensulin M40, Gensulin M30). The aim of an X-band (9.3GHz) study was comparative
      analysis of antioxidative properties of the three groups of human insulins. DPPH
      was used as a stable free radical model. Amplitudes of EPR lines of DPPH as the
      paramagnetic free radical reference, and DPPH interacting with the individual
      tested insulins were compared. For all the examined insulins kinetics of their
      interactions with free radicals up to 60 min were obtained. The strongest
      interactions with free radicals were observed for the short-acting insulin -
      Insuman Rapid. The lowest interactions with free radicals were characteristic for
      intermediate-acting insulin - Insuman Basal. The pre-mixed insulins i.e. Humulin
      M3 and Gensulin M50 revealed the fastest interactions with free radicals. The
      short acting, intermediate acting and premixed insulins have been found to be
      effective agents in reducing free radical formation in vitro and should be
      further considered as potential useful tools in attenuation of oxidative stress
      in diabetic patients.

PMID- 25975233
TI  - Downregulation of urinary cell-free microRNA-214 as a diagnostic and prognostic
      biomarker in bladder cancer.
AB  - BACKGROUND AND OBJECTIVES: We aimed to investigate potential of urinary cell-free
      microRNA-214 (miR-214) as a noninvasive biomarker for bladder cancer in this
      report. METHODS: We screened miR-214 expression in medium from 2 bladder cancer
      cell lines to determine whether it is secretory. Then we validated expression of
      cell-free miR-214 in urine samples from an independent set of 192 preoperative
      bladder cancer patients, 80 matching postoperative patients and 169 healthy
      controls. RESULTS: miR-214 was secreted from bladder cancer cell lines. Cell-free
      miR-214 levels were significantly attenuated in preoperative urine from bladder
      cancer patients, whereas its expression significantly increased in matched
      postoperative urine. Underexpressed extracellular miR-214 in urine was
      significantly associated with higher tumor stage, higher lymph node status,
      higher grade, age and history of non-muscle-invasive bladder cancer (NMIBC).
      Urinary cell-free miR-214 could forcefully differentiate bladder cancer (area
      under the curve; AUC = 0.838; 95% CI = 0.796-0.875) patients from healthy
      controls. Additionally, miR-214 in urine supernatant could serve as an
      independent prognostic predicator of recurrence-free survival (RFS) and overall
      survival (OS) for patients with muscle-invasive bladder cancer (MIBC).
      CONCLUSIONS: Urinary cell-free miR-214 is a hopeful biomarker for tumor
      stratification, early diagnosis and prognostic assessment of bladder cancer.

PMID- 25975234
TI  - Rabbit as an animal model for intravitreal pharmacokinetics: Clinical
      predictability and quality of the published data.
AB  - Intravitreal administration is the method of choice in drug delivery to the
      retina and/or choroid. Rabbit is the most commonly used animal species in
      intravitreal pharmacokinetics, but it has been criticized as being a poor model
      of human eye. The critique is based on some anatomical differences, properties of
      the vitreous humor, and observed differences in drug concentrations in the
      anterior chamber after intravitreal injections. We have systematically analyzed
      all published information on intravitreal pharmacokinetics in the rabbit and
      human eye. The analysis revealed major problems in the design of the
      pharmacokinetic studies. In this review we provide advice for study design.
      Overall, the pharmacokinetic parameters (clearance, volume of distribution, half
      life) in the human and rabbit eye have good correlation and comparable absolute
      values. Therefore, reliable rabbit-to-man translation of intravitreal
      pharmacokinetics should be feasible. The relevant anatomical and physiological
      parameters in rabbit and man show only small differences. Furthermore, the
      claimed discrepancy between drug concentrations in the human and rabbit aqueous
      humor is not supported by the data analysis. Based on the available and properly
      conducted pharmacokinetic studies, the differences in the vitreous structure in
      rabbits and human patients do not lead to significant pharmacokinetic
      differences. This review is the first step towards inter-species translation of
      intravitreal pharmacokinetics. More information is still needed to dissect the
      roles of drug delivery systems, disease states, age and ocular manipulation on
      the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data
      and the derived pharmacokinetic parameters indicate that the rabbit is a useful
      animal model in intravitreal pharmacokinetics.

PMID- 25975235
TI  - Unusual high fluorescence of two nitro-distyrylbenzene-like compounds induced by
      CT processes affecting the fluorescence/intersystem-crossing competition.
AB  - Two nitro-substituted 1,4-distyrylbenzene-like compounds have been investigated
      using stationary and time-resolved (ns/fs) spectrometric techniques as a function
      of solvent polarity. In the two compounds the central benzene ring is substituted
      with a p-nitrostyryl group at one side while, at the other side, compound 1
      (asymmetric) bears a pyrid-4-ylethenyl group and compound 2 (symmetric) another p
      nitrostyryl group. The solvent dependent intramolecular charge transfer (ICT) in
      the singlet manifold was found to strongly affect the competition among
      fluorescence, intersystem crossing and trans-cis photoisomerization. The presence
      of nitro-groups in the 1,4-distyrylbenzene skeleton causes the usual strong
      decrease of fluorescence in favour of intersystem crossing to a reactive triplet
      state. However, the favoured formation of the ICT state in polar solvents induces
      an unexpected important increase of the fluorescence quantum yield (three/two
      order of magnitude for the nitro and dinitro derivatives, respectively). The
      ultrafast spectral transients helped to understand the solvent effects measured
      by stationary techniques and gave information on the dynamics of the locally
      excited singlet state ((1)LE*) and the (1)ICT* state, fast produced in polar
      solvents. Evidence of dual fluorescence in a limited range of solvent polarity,
      particularly for compound 1, is also reported. The role of an upper triplet state
      in a non-polar solvent is discussed also based on quantum-mechanical calculations
      (TD-DFT method) and temperature effects on the photophysical parameters.

PMID- 25975236
TI  - Natural radionuclides in soil near a coal-fired power plant in the high
      background radiation area, South China.
AB  - In this study, soil samples around Mawan coal-fired power plant (CFPP) in
      Shenzhen, a high background radiation area in South China, were analyzed for
      natural radionuclides. The activity concentration of (226)Ra, (232)Th, and (40)K
      in soils around Mawan CFPP ranged from approximately 72 to 358 Bq kg(-1)
      (averaged 204 Bq kg(-1)), 118 to 432 Bq kg(-1) (averaged 265 Bq kg(-1)), and 101
      to 2168 Bq kg(-1) (averaged 1269 Bq kg(-1)), respectively, being found to be
      significantly higher than the world range values. The levels of these
      radionuclides in soil largely decreased with increasing distance from the CFPP,
      indicating a technologically enhanced natural radiation near the CFPP. The Raeq
      values for the soil samples around Mawan CFPP ranged from 346 to 878 Bq kg(-1),
      most of which exceeded the allowed maximum Raeq value of 370 Bq kg(-1). The
      operating of CFPP has increased the total radioactive dose received for the
      nearby population.

PMID- 25975237
TI  - The consequences of disposing wastewater in an endorheic wetland in southwest
      Iran.
AB  - Wetlands are important ecosystems both at regional and global scales. They are
      home to a diverse group of flora and fauna, and provide water for drinking,
      irrigation, and recreational purposes. Miangaran endorheic wetland in SW Iran
      serves as the discharge point of the municipal wastewater of a nearby city; it
      receives agricultural return flows as well. To identify the consequences of the
      wastewater input, 29 water samples from the wetland's body and inlet streams were
      analyzed for physico-chemical parameters. The average EC of the wetland was 405
      MUS/cm; calcium, magnesium, and bicarbonate were the dominant ions. The average
      pH was high, about 8.6, due to carbonate dissolution in the drainage area which
      was exacerbated by photosynthesis process inside the wetland. The concentration
      of phosphate was over the eutrophication limit of 0.1 mg/L. Nitrate contents
      varied from 5.7 to 12.3 mg/L. Trophic state index based on total nitrogen was
      about 63, falling within the eutrophic group. Heavy metal concentrations were
      generally higher than WHO drinking limits. Highest values of EC, nutrients, and
      metals were observed in the south and northwest, clearly signifying the role of
      wastewater input as the main source of contamination, which has resulted in the
      eutrophication of the wetland.

PMID- 25975239
TI  - Soil-to-plant transfer of native selenium for wild vegetation cover at selected
      locations of the Czech Republic.
AB  - Total selenium (Se) contents were determined in aboveground biomass of wild plant
      species growing in two uncultivated meadows at two different locations. The soils
      in these locations had pseudototal (Aqua Regia soluble) Se in concentration
      ranges of between 0.2 and 0.3 mg kg(-1) at the first location, and between 0.7
      and 1.4 mg kg(-1) at the second location. The plant species represented 29 plant
      families where the most numerous ones were Poaceae, Rosaceae, Fabaceae , and
      Asteraceae. The selenium contents in the plants varied between undetectable
      levels (Aegopodium podagraria, Achillea millefolium, Lotus corniculatus) and
      0.158 mg kg(-1) (Veronica arvensis, Veronicaceae). The Se levels were roughly one
      order of magnitude lower compared to other elements with similar soil content,
      such as cadmium and molybdenum. The transfer factors of Se, quantifying the
      element transfer from soil to plants, varied between <0.001 and 0.146 with no
      significant differences between the locations, confirming the limited soil-plant
      selenium transfer regardless of location, soil Se level, and plant species. Among
      the plant families, no unambiguous trend to potential elevated Se uptake was
      observed. Low Se content in the soil and its plant availability was comparable to
      other Se-deficient areas within Europe.

PMID- 25975238
TI  - Coke workers' exposure to volatile organic compounds in northern China: a case
      study in Shanxi Province.
AB  - China is the largest coke producer and exporter in the world, and it has been a
      major concern that large populations of coke workers are exposed to the
      associated air pollutants such as volatile organic compounds (VOCs). This study
      aimed to preliminarily quantify the potential exposure to VOCs emitted from two
      representative coking plants and assess the potential health risks. Air samples
      from various stages of coking were collected from the topside of coke ovens and
      various plant areas and then analyzed for benzene, toluene, ethylbenzene, and
      xylene (BTEX). The time-weighted average (TWA) concentrations were used to
      quantify the coke oven emission (COE). The TWA concentrations for benzene were
      705.6 and 290.4 MUg m(-3) in plant A and plant B, respectively, which showed a
      higher exposure level than those reported in other countries. COE varied on the
      topside of coke ovens during charging and pushing processes, from 268.3 to 1197.7
      MUg m(-3) in plant A and 85.4-489.7 MUg m(-3) in plant B. Our results indicate
      that benzene exposure from the diffusion of tar distillation also exerts
      significant health risks and thus should also be concerned. Charging and pushing
      activities accounted for nearly 70 % of benzene dose at the topside, and the
      benzene exposure risks to the coke oven workers in China were higher than those
      reported by US EPA. Compared to the reported emission sources, the weight-based
      ratios of average benzene to toluene, ethylbenzene, and xylene in different COE
      air samples showed unique characteristic profiles. Based on the B/T ratios from
      this work and from literatures on several major cities in northern China, it was
      evident that COE contributes significantly to the severe pollution of VOCs in the
      air of northern China. Future more rigorous studies are warranted to characterize
      VOC emission profiles in the stack gas of the coking processes in China.

PMID- 25975240
TI  - HLA-DRB and HLA-DQ genetic variability in patients with aspirin-exacerbated
      respiratory disease.
AB  - BACKGROUND: Major histocompatibility complex (MHC) class II is involved in T-cell
      activation, cytokine secretion, and induction of immune responses. Cytokines,
      staphylococcus super antigens, and eosinophil activation are proposed to play
      important roles in aspirin-exacerbated respiratory disease (AERD). OBJECTIVES:
      This study is aimed at investigating the association of HLA-DRB and DQ genetic
      variabilities in patients with AERD. METHODS: A genetic association analysis in
      three different groups, including 33 patients with AERD, 17 patients with aspirin
      tolerant asthma (ATA), and 100 healthy controls was performed. Oral aspirin
      challenge (OAC) test was performed to identify aspirin hypersensitivity.
      Pulmonary function test (PFT) was performed for all patients. Eosinophil
      percentage in nasal smear and peripheral blood and serum immunoglobin (Ig)E were
      investigated. HLA-DRB, HLA-DQA1, and HLA-DQB1 were genotyped using polymerase
      chain reaction. RESULTS: HLA-DQB1*0302 (OR, 5.49, 95% confidence interval
      [CI],(2.40-12.59)), HLA-DQA1*0301 (OR, 2.90, 95% CI, (1.49-5.67)), HLA-DRB4 (OR,
      2.94, 95% CI, (1.61-5.36)), and HLA-DRB1*04 (OR, 3.19, 95% CI, (1.57-6.47)) were
      higher in patients with AERD compared with controls. In patients with AERD, HLA
      DQB1*0301 (OR,0.22, 95% CI, (0.09-0.54)), HLA-DQA1*0501 (OR, 0.42, 95% CI, (0.21
      0.81)), HLA-DRB1*11 (OR, 0.30, 95% CI, (0.12-0.73)), and HLA-DRB3 (OR, 0.38, 95%
      CI, (0.21-0.70)) were significantly lower compared with healthy controls.
      Patients with AERD had lower frequencies of HLA-DQB1*0301 (OR, 0.27, 95% CI,
      (0.08-0.86)), and HLA-DRB1*011 (OR, 0.27, 95% CI, (0.08-0.86)) compared with ATA.
      Haplotypes of HLA-DRB1*04/ DQA1*0301/ DQB1*0302 (OR, 4.25, 95% CI, (1.94-9.29))
      and HLA-DRB1*07 /DQA1*0201/ DQB1*0201 (OR, 3.52, 95% CI, (1.54-8.06)) were higher
      in patients with AERD compared with controls (all p < 0.05). CONCLUSIONS: Results
      of this study suggest that HLA-DQB1*0302 and HLA-DRB1*04 and their related
      haplotypes are genes involved in predisposing patients to AERD, whereas HLA
      DQB1*0301 and HLA-DRB1*011 have negative association with AERD.

PMID- 25975241
TI  - Prevalence of chronic rhinosinusitis in a population of patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND: An increased coexistence of gastroesophageal reflux disease (GERD)
      and chronic rhinosinusitis (CRS) has been reported in epidemiologic and register
      studies, and reflux has been shown more frequently in patients with CRS in
      studies using esophagus pH manometry compared to participants without CRS. A
      discussion is ongoing about whether there might be an association between these
      two diseases and, if so, whether the association is causal. OBJECTIVE: The
      purpose of this study was to clinically investigate the prevalence and symptom
      severity scores of CRS among patients with GERD. The results were compared with
      those of a randomly assigned control group from the general Danish population.
      METHOD: In this case-control study, 82 patients with GERD were examined for CRS
      using the European Position Paper on Rhinosinusitis and Nasal Polyps criteria,
      which combine patient history and anterior/posterior rhinoscopy results.
      Sinonasal-related quality of life was assessed by using the Sino-Nasal Outcome
      Test 22 (SNOT-22). These results were compared with those of a population-based
      control group examined for CRS in the same way. RESULTS: The prevalence of CRS
      among patients with GERD was 20.7% (95% confidence interval [CI], 12.0%-29.5%),
      significantly higher than the CRS prevalence of 8.5% (95% CI, 6.8%-10.2%) in the
      background population. Patients with GERD and CRS had an average SNOT-22 score of
      43.8, whereas patients with CRS from the background population scored, on
      average, 28.1. Having GERD increased the mean SNOT-22 score in patients with CRS
      by 15.7 (95% CI, 6.5-24.9). CONCLUSION: The results of this study provide
      additional evidence of an association between GERD and CRS and indicate that GERD
      may play a role in the development of CRS. The results also show that sinonasal
      related quality of life is decreased in patients with CRS who also suffer from
      GERD.

PMID- 25975242
TI  - Chronic obstructive pulmonary disease predicts chronic rhinosinusitis without
      nasal polyps: A population-based study.
AB  - BACKGROUND: Few studies have investigated the relationship between chronic
      obstructive pulmonary disease (COPD) and chronic rhinosinusitis without nasal
      polyps (CRSsNP) outcomes. The aim of this study was to investigate the
      association between COPD and the risk of CRSsNP in a large national sample.
      METHODS: Patients 15 years or older with a new primary diagnosis of COPD
      (International Classification of Diseases, Ninth edition [ICD-9], 491, 492, 494,
      and 496) between 2000 and 2007 were identified from the National Health Insurance
      Research Database of Taiwan. The patients were compared with sex-, age-,
      residence-, and insurance premium-matched controls, and both groups were followed
      up until the end of 2008 for instances of CRSsNP, defined as ICD-9 codes CRS
      (473, 473.0, 473.1, 473.2, 473.3, 473.8, and 473.9), excluding NP (471, 471.0,
      471.1, 471.8, and 471.9). Competing risk-adjusted Cox regression analyses were
      applied after adjusting for sex, age, residence, insurance premium, steroid use
      (topical or systemic), hyperlipidemia, diabetes, hypertension, coronary artery
      disease, hospital admission days, and mortality. RESULTS: We included 34,029
      cases and 34,029 matched controls in this study. Among the 68,058 subjects, 569
      developed CRSsNP during a mean (standard deviation [SD]) follow-up period of 5.0
      years (SD 2.2 years). COPD was an independent predictor of CRSsNP in the fully
      adjusted model (hazard ratio = 3.24; 95% CI = 2.65-3.96; p < 0.01). CONCLUSION:
      COPD was associated with an increased risk of CRSsNP in this study population,
      independent of a number of potential confounding factors.

PMID- 25975243
TI  - Role of Wnt signaling pathway in progression of sinonasal inverted papilloma to
      squamous cell carcinoma.
AB  - BACKGROUND: Sinonasal inverted papilloma (IP) is one of the most common benign
      tumors of the sinonasal area and malignant transformation has frequently been
      reported. However, the exact mechanism of the transition from benign lesion to
      malignancy is not known. The Wnt signaling pathway involves a network of multiple
      signaling glycoproteins that are known to play an important role in embryogenesis
      and carcinogenesis. OBJECTIVE: The purpose of this study was to evaluate the role
      of the Wnt pathway and signaling proteins in malignant transformation of IP to
      dysplasia and squamous cell carcinoma. METHODS: Expression of the Wnt signaling
      pathway proteins, including Wnt-1, beta-catenin, cyclin D1, and Dishevelled-1
      (Dvl-1), were detected by immunohistochemistry by using 3-mm tissue core
      microarrays that consisted of 115 cores of IP tissue. Each of the IP cores was
      graded as I (prominent squamous metaplasia), II (inverted pattern), III
      (dysplasia), or IV (squamous cell carcinoma). The expression pattern of each
      protein and the correlation between the expression of each target protein and IP
      grade were evaluated. RESULTS: Membranous staining of beta-catenin showed a
      significant positive correlation with IP grade (rho = 0.247, p < 0.001), as did
      staining of cyclin D1 (rho = 0.365, p < 0.001), which showed a nuclear pattern
      and staining of Dvl-1 (rho = 0.380, p < 0.001), which showed a membranous,
      cytoplasmic, and nuclear pattern. For Dvl-1, a nuclear expression pattern was
      more frequently observed in grade III and IV IP (p = 0.036). In the case of Wnt
      1, cytoplasmic expression was observed; however, it did not show a significant
      correlation with IP grade (rho = 0.141, p = 0.130). CONCLUSIONS: Wnt signaling
      proteins, including beta-catenin, cyclin D1, and Dvl-1, may play crucial roles in
      the malignant transformation of IP.

PMID- 25975244
TI  - Protective effects of rutin through regulation of vascular endothelial growth
      factor in allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is an allergic inflammatory disease induced by
      various mediators released by infiltrating inflammatory cells. Vascular
      endothelial growth factor (VEGF) increases the airway inflammatory response by
      promoting vascular permeability. Furthermore, it is known that Allium hookeri and
      one of its constituent compounds, rutin (RU), have anti-inflammatory,
      antioxidant, and antiplatelet effects. OBJECTIVE: The aim of this study was to
      evaluate the regulation of AR by RU and A. hookeri. METHODS: We assessed the
      therapeutic effects and the regulatory mechanisms of A. hookeri and RU on phorbol
      12-myristate 13-acetate plus A23187 (PMACI) stimulated human mast cell line (HMC)
      1 cells, and ovalbumin (OVA) sensitized mouse model of AR. RESULTS: A. hookeri
      and RU significantly inhibited the production and messenger RNA (mRNA) expression
      of VEGF in PMACI-stimulated HMC-1 cells and significantly decreased VEGF levels
      in our murine AR model. The increased rubs scores and immunoglobulin E and
      interleukin (IL) 4 levels in OVA-sensitized mice were significantly reduced by
      the administration of A. hookeri, and RU significantly inhibited the production
      and mRNA expression and RU. Also, A. hookeri and RU significantly reduced IL-4
      and IL-5 production in OVA-stimulated splenocytes. Furthermore, A. hookeri and RU
      significantly decreased chemokine levels (intercellular adhesion molecule-1,
      macrophage inflammatory protein-2) in nasal mucosa tissues. In the mouse AR
      model, A. hookeri and RU significantly prevented eosinophil and mast cell
      infiltration and reduced inflammatory cytokine levels induced by OVA
      sensitization. In addition, A. hookeri and RU significantly reduced mast cell
      derived caspase-1 activity in OVA-sensitized mice. CONCLUSION: The present study
      showed that A. hookeri or RU had an anti-allergic inflammatory effects. Analysis
      of these results indicated that A. hookeri and RU might protect against AR.

PMID- 25975245
TI  - Advancing the field of rhinology and allergy.

PMID- 25975246
TI  - Asian sand dust increases MUC8 and MUC5B expressions via TLR4-dependent ERK2 and
      p38 MAPK in human airway epithelial cells.
AB  - BACKGROUND: Asian sand dust (ASD) is a natural phenomenon and originates from the
      deserts of China and is known to contain various chemical and biomolecular
      components that enhance airway inflammation. The overproduction of airway mucins
      is an important pathologic finding in inflammatory airway diseases. However, the
      mechanism of ASD on mucin production of airway epithelial cells has not been
      elucidated. OBJECTIVE: To investigate the effect and signaling pathway of ASD on
      mucin expressions in human airway epithelial cells. METHODS: In the NCI-H292
      cells and the primary cultures of human nasal epithelial cells, the effect and
      signaling pathway of ASD on MUC8 and MUC5B expressions were investigated using
      reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme
      immunoassay, and immunoblot analysis with several specific inhibitors and small
      interfering RNA (siRNA). RESULTS: ASD increased MUC8 and MUC5B expressions and
      activated the phosphorylations of extracellular signal-regulated kinase 1/2
      (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (ERK1/2 MAPK
      inhibitor) and SB203580 (p38 MAPK inhibitor) inhibited ASD-induced MUC8 and MUC5B
      expressions. In addition, knockdowns of ERK2 and p38 MAPK by siRNA blocked ASD
      induced MUC8 and MUC5B mRNA expressions. Toll-like receptor 4 (TLR4) mRNA
      expression was increased after treatment with ASD. Knockdown of TLR4 by siRNA
      blocked ASD-induced MUC8 and MUC5B mRNA expressions. Furthermore, the
      phosphorylations of ERK1/2 and p38 MAPK were blocked by knockdown of TLR4.
      CONCLUSIONS: These results show that ASD induces MUC8 and MUC5B expressions via
      TLR4-dependent ERK2 and p38 MAPK signaling pathway in human airway epithelial
      cells.

PMID- 25975247
TI  - Volumetric analysis of chronic maxillary atelectasis.
AB  - BACKGROUND: The relationship between orbit and maxillary sinus volumes in
      patients with chronic maxillary atelectasis (CMA), commonly known as silent sinus
      syndrome if enophthalmos is present, is poorly understood. METHODS: A
      retrospective review of 22 patients who underwent endoscopic sinus surgery (ESS)
      for CMA from 2005 to 2013 was performed. Computed tomography (CT) images were
      analyzed using OsiriX 5.8.2 software for volumetric analysis of the orbit and
      maxillary sinus at presentation and after surgical treatment with ESS. RESULTS:
      Pretreatment mean orbit volumes on the diseased side (DS) and the contralateral
      side (CS) were 29.22 and 26.50 mL, respectively (p < 0.001); mean sinus volumes
      on the DS and CS were 8.51 and 17.20 mL, respectively (p < 0.001); and
      pretreatment mean midorbit heights (MOHs) on the DS and CS were 3.39 cm and 3.07
      cm, respectively (p < 0.001). The percent decrease in sinus volume on the DS
      compared to that on the CS did not correlate significantly with the percent orbit
      volume increase. Enophthalmos was present in nine (41%) patients, and diplopia
      was present in three (14%) patients. The measured degree of increased orbit
      volume and decreased sinus volume secondary to CMA did not significantly predict
      the presence of enophthalmos at presentation. Seven patients underwent sinus CT
      more than 6 months after ESS. In these patients, orbit volume on the DS decreased
      from 29.67 to 27.52 mL (p = 0.005), and sinus volume on the DS increased from
      9.78 to 11.84 mL (p = 0.08). CONCLUSIONS: Volumetric analysis is a powerful and
      novel method for objectively demonstrating the degree of orbit expansion and
      maxillary sinus contraction seen with CMA. Spontaneous maxillary sinus expansion
      and a decrease in orbit volume can occur after ESS, but post-ESS volumes do not
      return to the normal volume of the CS.

PMID- 25975248
TI  - Interleukin-25 and interleukin-33 as mediators of eosinophilic inflammation in
      chronic rhinosinusitis.
AB  - BACKGROUND: The initiating mediators of T-helper 2 inflammation, often seen in
      eosinophillic chronic rhinosinusitis (CRS), remains poorly understood.
      Interleukin (IL) 25, IL-33, and thymic stromal lymphopoietin (TSLP) are
      epithelial-derived cytokines implicated in the initiation of T-helper 2
      inflammation and eosinophilia in other diseases. The expression of these
      cytokines was compared with phenotypic and histopathologic markers to investigate
      the factors that may drive eosinophilic inflammation in CRS. METHOD: Sinus
      mucosal samples from patients with CRS who were undergoing sinus surgery as part
      of their management were analyzed for IL-25, IL-33, and TSLP messenger RNA (mRNA)
      expression by quantitative polymerase chain reaction. Patients with tumor and who
      were undergoing surgery via an endonasal approach with normal sinus mucosa were
      controls. The mRNA expression was compared with CRS phenotype and histopathologic
      measures of eosinophilic inflammation. Immunohistochemical staining was used to
      confirm mRNA expression. RESULTS: Thirty-nine patients (mean +/- standard
      deviation age; 48.2 +/- 15.0 years, 38% women), 12 patients with CRS with nasal
      polyps, 20 patients with CRS without nasal polyps, and 7 controls were recruited.
      Higher IL-25 (p = 0.005) and IL-33 (p = 0.003) mRNA and protein expression was
      observed in patients with >10 eosinophil/hpf. TSLP showed no significant
      associations (p = 0.39). Similar overexpression was seen in eosinophilic
      dominated inflammation (IL-25, p = 0.01; IL-33, p = 0.02) and patients with
      greater inflammatory severity. CONCLUSION: IL-25 and IL-33 overexpression was
      observed in eosinophilic CRS, The release of these cytokines by dysfunctional
      endothelium may perpetuate the eosinophillic inflammation in CRS.

PMID- 25975249
TI  - Increased phosphorylation of STAT5b, but not STAT5a, in nasal polyps.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent,
      benign, extensively proliferating disease that is triggered by inflammation. The
      signaling pathways in sinusitis and the regulation by intracellular signaling
      peptides and proteins are not fully understood. Signal transducer and activator
      of transcription (STAT) 5a and STAT5b are two closely related phosphokinases
      involved in the regulation of diverse cellular functions, including proliferation
      and apoptosis. OBJECTIVE: The objective of the study was to investigate the
      expression, activation, and distribution of STAT5 Transcription factor in CRSwNP.
      METHODS: We studied these transcription factors in tissue samples of nasal polyps
      and inferior turbinates from a total of 35 patients with CRSwNP and compared them
      with healthy nasal mucosa. The samples were analyzed by using a DNA microarray,
      quantitative real-time polymerase chain reaction, a protein array, immunoblot,
      immunoprecipitation and immunohistochemistry. RESULTS: We found equivalent
      overall expression of STAT5a in all tissue types. We observed an increase in the
      expression of STAT5b protein in both polyps and turbinates of patients with
      CRSwNP. In addition, STAT5b, but not STAT5a, was activated by phosphorylation in
      nasal polyps. Phosphorylated STAT5a/b was not detectable in the epithelium of
      turbinates from either patients with CRSwNP or patients with healthy mucosa, but
      it was clearly expressed in the epithelium of nasal polyps. CONCLUSION: Analysis
      of these data indicates distinct expression and activation of STAT5a and STAT5b
      in nasal polyps, particularly the activation of STAT5b. It is possible that
      STAT5b may contribute to the development of nasal polyps.

PMID- 25975250
TI  - Management of chronic rhinosinusitis with nasal polyps and coexisting asthma: A
      systematic review.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and asthma
      are strongly associated, and patients suffering from both diseases are often
      difficult to treat. However, no guidelines about the management of patients with
      CRS and coexisting asthma exist. OBJECTIVE: The purpose of this systematic review
      was to evaluate the management of CRSwNP and coexisting asthma. METHODS: We
      systematically searched electronic databases and included clinical trials in
      which the clinical outcomes after medical or surgical treatment of patients with
      CRSwNP and asthma were assessed. The strength of the evidence for each outcome
      was graded on the basis of study quality and consistency in findings. RESULTS: We
      included seven trials in which the effect of montelukast, omalizumab,
      erythromycin, and functional endoscopic sinus surgery (FESS) were studied in 317
      adults with CRSwNP and asthma. All the interventions improved the majority of
      subjective and objective nasal outcomes significantly. However, few studies found
      significant effects on pulmonary function tests. The strength of the evidence was
      low overall. CONCLUSION: Both FESS and medical interventions with systemic anti
      inflammatory drugs improved nasal outcomes, although their efficacy in relation
      to the lower airways remains unclear. A low number of studies met inclusion
      criteria for this systematic review, which emphasizes the need for high-quality
      trials to explore the treatment of patients with CRSwNP and coexisting asthma.

PMID- 25975251
TI  - Higher antineutrophil cytoplasmic antibody (C-ANCA) titers are associated with
      increased overall healthcare use in patients with sinonasal manifestations of
      granulomatosis with polyangiitis (GPA).
AB  - BACKGROUND: Granulomatosis with polyangiitis (GPA) is an autoimmune disease
      characterized by necrotizing granulomatous airway inflammation and vasculitis.
      Sinonasal involvement occurs in more than 80% cases, with antineutrophil
      cytoplasmic antibody (C-ANCA) titers used as a marker of disease severity. The
      purpose of this study was to determine whether C-ANCA levels impact radiographic
      findings and healthcare use in patients with sinonasal GPA. METHODS: A
      retrospective review was performed on GPA patients evaluated in a
      multidisciplinary rheumatologic/otolaryngologic clinic from 2008 to 2013. Data
      were collected with respect to age, gender, clinical presentation, C-ANCA titers,
      Lund-Mackay (LM) scores, surgical interventions, and healthcare use, the latter
      of which were determined by assessing the number of rheumatology/otolaryngology
      clinic visits, computed tomography (CT) scans, and email/telephone encounters.
      RESULTS: A total of 44 patients were identified, 11 male and 33 female. Sinonasal
      manifestations were evident in 70.4%, with chronic rhinosinusitis (CRS) (41.9%),
      septal perforation (38.7%), and crusting (32.2%) the most common findings. No
      significant differences in number of CT scans (p = 0.10) or mean LM scores (p =
      0.47) were found between patients with more than or equal to 1:80 and less than
      1:80 C-ANCA titers, respectively. However, overall healthcare use was increased
      in the more than or equal to 1:80 C-ANCA group (n = 28) compared with less than
      1:80 (n = 16), with a significantly greater number of
      rheumatologic/otolaryngologic encounters (mean 121 versus 69.2, p = 0.03) noted.
      When otolaryngologic healthcare use was specifically examined, the average number
      of encounters was also higher in more than or equal to 1:80 C-ANCA patients (31.9
      versus 22.9), but this difference was not statistically significant (p = 0.16).
      CONCLUSION: Sinonasal GPA patients with presenting C-ANCA titers more than or
      equal to 1:80 demonstrated significantly greater overall healthcare use than
      their lower C-ANCA level counterparts (less than 1:80). However, no significant
      differences in otolaryngology resource use or LM scores were evident between the
      two titer groups.

PMID- 25975252
TI  - Managing cerebrospinal fluid rhinorrhea after lateral skull base surgery via
      endoscopic endonasal eustachian tube closure.
AB  - BACKGROUND: A cerebrospinal fluid (CSF) leak, commonly presenting as rhinorrhea,
      is a well-recognized complication of lateral skull base surgery. Failure of
      conservative treatment measures in these cases necessitates surgical
      intervention. OBJECTIVE: Our aim is to demonstrate that endoscopic endonasal
      closure of the eustachian tube is a reasonable alternative to more traditional
      techniques for management of recalcitrant postoperative CSF rhinorrhea after
      removal of middle and posterior cranial fossa lesions. METHODS: A retrospective
      chart review was performed for patients who presented with CSF rhinorrhea after
      lateral skull base surgery at a tertiary medical center over a 17-year period,
      from 1997 to 2014. Nine patients managed with endoscopic endonasal closure of the
      eustachian tube were evaluated for preoperative hearing status, approach to
      lateral skull base surgery, pathology, size and location of the tumor, timing and
      presentation of CSF leak, methods of treatment, length of hospital stay,
      complications, and success of the procedure. RESULTS: Of the nine patients
      included in this review, seven were managed successfully with endoscopic
      endonasal eustachian tube closure. Of those seven, one required a revision
      procedure. Average length of postoperative stay was 5.8 days. There were no major
      complications. Follow up of greater than 100 months has been achieved since the
      first procedure. CONCLUSION: Endoscopic endonasal eustachian tube closure is a
      safe, minimally invasive and effective method for obliteration of the eustachian
      tube orifice. The algorithm for management of recalcitrant postoperative CSF
      rhinorrhea after lateral skull base surgery should include endoscopic endonasal
      closure of the eustachian tube.

PMID- 25975253
TI  - Patterns and sequelae of sphenoid sinus fractures.
AB  - BACKGROUND: The sphenoid sinus is one of the most commonly fractured regions of
      the skull base after blunt head trauma. These fractures may be associated with
      complications such as blunt carotid artery injury (BCAI) and cerebrospinal fluid
      (CSF) leak. Association of these sequelae with sphenoid sinus fractures has yet
      to be analyzed thoroughly in the literature. OBJECTIVE: Analyze patterns of
      traumatic sphenoid sinus fractures and assess relationships between fracture
      patterns and incidence of BCAI and traumatic nasal CSF leaks. METHODS: A
      retrospective review of 123 patients sustaining sphenoid sinus fractures was
      performed. Patient medical records and radiographic images were reviewed.
      Fractures were classified based on the sinus walls involved. Logistic and linear
      regressions were used to analyze associations between injury mechanisms, fracture
      subsites, and sequelae. RESULTS: The most commonly fractured sphenoid sinus
      subsites included the carotid canal, sphenoid roof, and lateral wall (60%, 49%
      and 48%, respectively). CSF leaks occurred in 9% of sphenoid sinus fractures,
      whereas BCAI occurred in 1.6%. On logistic regression, sphenoid roof fractures
      were significantly associated with CSF leaks (odds ratio [OR] = 12.4, p = 0.002).
      No fracture subsite was associated with BCAI. The positive predictive value (PPV)
      of sphenoid roof fractures for the presence of CSF leaks was 17%, whereas the
      negative predictive value (NPV) was 98%. The PPV of carotid canal fractures for
      BCAI was 3%, whereas the NPV was 100%. There was no association between the
      number of fractured sinus walls and the incidence of BCAI or CSF leak.
      Penetrating injuries were significantly associated with CSF leak (OR = 24.7, p =
      0.01), but no other injury mechanisms were associated with BCAI or CSF leak.
      CONCLUSION: Nasal CSF leak was the most common sequela of sphenoid sinus
      fractures, whereas BCAI was extremely uncommon. Analysis of fracture patterns can
      be useful in determining the need for additional evaluation.

PMID- 25975254
TI  - The use of image-guidance during transsphenoidal pituitary surgery in the United
      States.
AB  - BACKGROUND: Intraoperative image guidance is a useful modality for
      transsphenoidal pituitary surgery. However, the outcomes associated with this
      technology have not been systematically evaluated. OBJECTIVE: The purpose of the
      study was to quantify complication rates with and without the use of image
      guidance during transsphenoidal pituitary surgery using a nationwide database
      with broadly applicable results. METHODS: A retrospective analysis of the
      Nationwide Inpatient Sample was performed from 2007 to 2011. Transsphenoidal
      pituitary resections for adenomas were identified by International Classification
      of Diseases-9th Revision, Clinical Modification code. The effect of image
      guidance on cerebrospinal fluid (CSF) leak complications and cost-benefit was
      analyzed. RESULTS: A total of 48,848 transsphenoidal pituitary resections were
      identified, of which 77.5% were partial resections and 22.5% were complete.
      Pathologic indications included benign (89.3%), malignant primary (0.6%), and
      malignant secondary (0.4%). Complications included same-stay death (0.4%), CSF
      leak (8.8%), postoperative CSF rhinorrhea (1.9%), diabetes insipidus (12.4%), and
      meningitis (0.4%). Image guidance was employed in 7% (n = 3401) of all cases.
      When analyzed by modality, computed tomography (CT)-assisted procedures had lower
      CSF rhinorrhea rates (1.1%) compared with cases with no image guidance (1.9%),
      whereas magnetic resonance (MR)-assisted procedures had the highest rates (2.7%,
      chi2 p < 0.001). Rates of CSF leak demonstrated a similar pattern (CT 6.4%, no
      image guidance 8.9%, MR 9.2%, chi2 p < 0.001). CT-assisted surgery had
      significantly shorter length of stay (2.9 days) versus no image guidance (3.7
      days, p < 0.001), lower total charges ($47,589 versus $62,629, p < 0.001), and
      lower total cost ($16,748 versus $20,530, p < 0.001). CONCLUSIONS: CT-assisted
      surgery is associated with a lower rate of CSF leak, shorter length of stay, and
      lower cost compared with patients without image guidance. Further studies that
      control for severity and extent of disease are warranted to confirm this finding.

PMID- 25975255
TI  - Endoscopic binostril versus transnasal transseptal microscopic pituitary surgery:
      Sinonasal quality of life and olfactory function.
AB  - BACKGROUND: There have been few comparative studies on olfactory function and
      sinonasal-specific quality of life (QOL) after endoscopic or microscopic surgery
      using a transsphenoidal approach (TSA). METHODS: A retrospective review of a
      prospectively collected database was performed. Thirty-five patients who
      underwent a transnasal endoscopic approach and 20 patients who underwent a
      transnasal transseptal microscopic approach for treatment of pituitary adenoma
      were evaluated. An anterior skull base (ASK) nasal inventory and a subjective
      visual analog scale (VAS) (0-100) for olfaction were evaluated before and at one
      and three months after surgery. A cross-cultural smell identification test (CC
      SIT) and a butanol threshold test (BTT) were also measured before and three
      months after surgery. RESULTS: There was no significant difference in subjective
      olfaction or CC-SIT or BTT score between the endoscopic and microscopic groups.
      The microscopic group (11.35 +/- 3.67 and 9.72 +/- 2.54, respectively) showed
      better ASK nasal inventory outcomes at one and three months after surgery
      compared with the endoscopic group (14.00 +/- 4.85 and 11.70 +/- 3.28,
      respectively; p = 0.029 and 0.036, respectively) especially in the subdomains of
      "nasal crusting" and "urge to blow nose." CONCLUSION: Transnasal transseptal
      microscopic pituitary surgery confers a better early postoperative sinonasal QOL
      with a comparable olfactory outcome compared with the endoscopic approach.
      Although many believe that an endoscopic approach is less invasive, preservation
      of the sinonasal mucosa proves to be more important in terms of sinonasal QOL
      than use of an endoscope or microscope.

PMID- 25975256
TI  - Radiofrequency ablation for treatment of hereditary hemorrhagic telangiectasia
      lesions: "How I do it".
AB  - INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) can cause significant
      epistaxis for those that suffer from it. Traditaional surgical treatments are
      ablative and can cause thermal damage. Radiofrequency (RF) energy can potentially
      be used to ablate HHT plaques at a lower temperature. In this article we describe
      our use of RF energy to treat HHT. METHODS: A Coblation Evac70 wand was used with
      patients under general anesthetic to ablate visible lesions. The surgical
      technique is described in detail. RESULTS: Thirty-seven patients have been
      treated over a 3-year time span showing significant improvement in epistaxis
      severity as measured by the Epistaxis Severity Score. There were three septal
      perforations that developed, but these were all in patients who had undergone
      several prior septal cauteries. CONCLUSION: RF energy via Coblation is an
      effective and safe means of surgically treating HHT lesions, with good epistaxis
      severity improvement and minimal patient morbidity.

PMID- 25975259
TI  - Soluble VE-cadherin is involved in endothelial barrier breakdown in systemic
      inflammation and sepsis.
AB  - AIMS: Microvascular endothelial barrier breakdown in sepsis precedes organ
      failure and death in patients. We tested the hypothesis that the formation of
      endothelium-derived soluble vascular endothelial (VE)-cadherin fragments (sVE
      cadherin) is involved in inflammation-induced endothelial barrier disruption.
      METHODS AND RESULTS: Incubation of human dermal microvascular endothelial cells
      (HDMEC) with tumour necrosis factor-alpha (TNF-alpha) and bacterial
      lipopolysaccharide (LPS) led to endothelial barrier disruption which correlated
      with significantly increased sVE-cadherin at a size of ~90 kDa in cell culture
      supernatants. Inhibition of the VE-cadherin-cleaving disintegrin and
      metalloproteinase ADAM10 using GI254023X attenuated inflammation-induced
      formation of sVE-cadherin and endothelial barrier disruption, suggesting ADAM10
      mediated shedding as a mechanism underlying sVE-cadherin release. Formation of VE
      cadherin fragments at 90 and 110 kDa was observed when recombinant VE-cadherin
      (rVE-cadherin) was digested with recombinant ADAM10. Mass spectrometry of the VE
      cadherin fragments showed that they originated from cleavage of the extracelluar
      domain and thereby several cleavage sites of ADAM10 were identified. Atomic force
      microscopy measurements demonstrated that cell culture supernatants containing
      sVE-cadherin and application of rVE-cadherin blocked VE-cadherin binding.
      Accordingly rVE-cadherin dose-dependently led to loss of endothelial barrier
      functions in HDMEC monolayers. Finally, in patients suffering from severe sepsis
      or septic shock with clinical signs of a microvascular leackage, serum levels of
      sVE-cadherin were significantly increased. CONCLUSION: Taken together, formation
      of sVE-cadherin is associated and contributes to inflammation-induced breakdown
      of endothelial barrier functions by inhibition of VE-cadherin binding. The
      underlying mechanism of VE-cadherin cleavage involves ADAM10 and appears to be of
      clinical relevance since sVE-cadherin was augmented in patients with severe
      sepsis.

PMID- 25975260
TI  - Soluble Notch ligand and receptor peptides act antagonistically during
      angiogenesis.
AB  - AIMS: Notch signalling is essential for blood vessel formation. During
      angiogenesis, the Notch ligand DLL4 on the leading tip cell activates Notch
      receptors on the adjacent stalk cells. DLL4-Notch signalling is impaired by the
      Notch ligand JAG1 in endothelial cells. The Delta/Serrate/Lag2 (DSL) domain of
      the Notch ligands binds to the EGF-like repeats 11-13 of the Notch receptor. This
      study aimed to elucidate how soluble proteins containing these short domains
      interfere with Notch signalling during angiogenesis. METHODS AND RESULTS:
      Adenoviral vectors were generated to express the DSL domains of DLL1, DLL4, JAG1,
      and the Notch1 EGF-like repeats 11-13 fused to immunoglobulin-G heavy chain.
      These soluble ligand peptides inhibited Notch signalling in endothelial cells and
      this caused hyperbranching in cellular angiogenesis assays and in the neonatal
      mouse retina. The soluble Notch receptor peptides bound stronger to JAG1 than
      DLL4 ligands, resulting in increased signalling activity. This led to impaired
      tip cell formation and less vessel sprouting in the retina. CONCLUSION: The
      minimal binding domains of Notch ligands are sufficient to interfere with Notch
      signalling. The corresponding soluble Notch1 EGF11-13 peptide binds stronger to
      inhibitory Notch ligands and thereby promotes Notch signalling in endothelial
      cells.

PMID- 25975261
TI  - Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src
      signaling.
AB  - Src family tyrosine kinase (SFK) activation is associated with ovarian cancer
      progression. Therefore, SFKs are targets for the development of potential
      treatments of ovarian cancer. Dasatinib is a tyrosine kinase inhibitor that
      targets SFK activity, and is used for the treatment of B cell and Abelson
      lymphomas. At the present time, the potential effect of dasatinib on ovarian
      cancer is not clear. The aim of the present study was to investigate the
      antitumor activity of dasatinib, alone and in combination with paclitaxel, in
      ovarian cancer in vitro and in vivo. In the present study, the expression of Src
      and phospho-Src-Y416 (p-Src) was measured in six ovarian cancer cell lines using
      western blotting and immunohistochemistry. In addition, cell viability and
      apoptosis were measured using an MTT assay and annexin V-fluorescein
      isothiocyanate staining. An ovarian cancer murine xenograft model was
      established, in order to evaluate the antitumor effect of dasatinib alone and in
      combination with paclitaxel in ovarian cancer. High levels of p-Src protein
      expression were observed in all cell lines, as compared with healthy cells, which
      indicated activation of the Src signaling pathway. p-Src expression increased in
      ovarian cancer cells following paclitaxel treatment. Dasatinib treatment
      demonstrated anti-ovarian cancer properties, by downregulating p-Src expression
      and by inducing cancer cell apoptosis. Combined treatment with dasatinib and
      paclitaxel markedly inhibited proliferation and promoted apoptosis of ovarian
      cancer cells, compared with control cells. Combined dasatinib and paclitaxel
      treatment exhibited antitumor activities in vivo and in vitro (combination
      indices, 0.25-0.93 and 0.31-0.75; and tumor growth inhibitory rates, 76.7% and
      58.5%, in A2780 and HO8910 cell lines, respectively), compared with paclitaxel
      treatment alone. Dasatinib monotherapy demonstrated anti-ovarian cancer
      activities. The effects of dasatinib and paclitaxel treatments on ovarian cancer
      cells appeared to be mediated by the Src pathway.

PMID- 25975262
TI  - Overexpression of P21-activated kinase 4 is associated with poor prognosis in non
      small cell lung cancer and promotes migration and invasion.
AB  - BACKGROUND: P21-activated kinase 4 (PAK4), an effector of the Rho family protein
      Cdc42, is an important oncogene whose expression is increased in many human
      cancers and is generally positively correlated with advanced disease and
      decreased survival. However, little is known about the expression and biological
      function of PAK4 in human non-small cell lung cancer (NSCLC). METHODS: PAK4
      expression in NSCLC tissues and adjacent non-tumor tissues were assessed by
      immunohistochemistry, real-time PCR, and western blotting. Prognostic value of
      PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. siRNA
      mediated gene silencing and protein kinase assay was applied to demonstrate the
      role and the mechanism of PAK4 in lung cancer cell migration, invasion. RESULTS:
      The results showed that PAK4 was overexpressed in NSCLC cell lines and human
      NSCLC tissues. PAK4 expression was detected both in the membranes and cytoplasm
      of NSCLC cancer cells in vivo. Moreover, increased expression of PAK4 was
      associated with metastasis, shorter overall survival, advanced stage of NSCLC.
      Furthermore, PAK4 expression was positively correlated with phosphorylation of
      LIMK1 expression levels. Knockdown of PAK4 in NSCLC cell lines led to reduce the
      phosphorylation of LIMK1, which resulted in decrease of the cell migration and
      invasion. In addition, PAK4 bound to LIMK1 directly and activated it via
      phosphorylation. CONCLUSIONS: These data demonstrate that PAK4 mediated LIMK1
      phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4
      might be a significant prognostic marker and potential therapeutic molecular
      target in NSCLC.

PMID- 25975263
TI  - Electrochemical Detection of Circadian Redox Rhythm in Cyanobacterial Cells via
      Extracellular Electron Transfer.
AB  - Recent research on cellular circadian rhythms suggests that the coupling of
      transcription-translation feedback loops and intracellular redox oscillations is
      essential for robust circadian timekeeping. For clarification of the molecular
      mechanism underlying the circadian rhythm, methods that allow for the dynamic and
      simultaneous detection of transcription/translation and redox oscillations in
      living cells are needed. Herein, we report that the cyanobacterial circadian
      redox rhythm can be electrochemically detected based on extracellular electron
      transfer (EET), a process in which intracellular electrons are exchanged with an
      extracellular electrode. As the EET-based method is non-destructive, concurrent
      detection with transcription/translation rhythm using bioluminescent reporter
      strains becomes possible. An EET pathway that electrochemically connected the
      intracellular region of cyanobacterial cells with an extracellular electrode was
      constructed via a newly synthesized electron mediator with cell membrane
      permeability. In the presence of the mediator, the open circuit potential of the
      culture medium exhibited temperature-compensated rhythm with approximately 24 h
      periodicity. Importantly, such circadian rhythm of the open circuit potential was
      not observed in the absence of the electron mediator, indicating that the EET
      process conveys the dynamic information regarding the intracellular redox state
      to the extracellular electrode. These findings represent the first direct
      demonstration of the intracellular circadian redox rhythm of cyanobacterial
      cells. 

PMID- 25975264
TI  - 8-Mercapto-Cyclic GMP Mediates Hydrogen Sulfide-Induced Stomatal Closure in
      Arabidopsis.
AB  - Plants are exposed to hydrogen sulfide (H2S) both exogenously, as it exists as a
      pollutant gas in the environment, and endogenously, as it is synthesized in
      cells. H2S has recently been found to function as a gaseous signaling molecule,
      but its signaling cascade remains unknown. Here, we examined H2S-mediated guard
      cell signaling in Arabidopsis. The H2S donor GYY4137 (morpholin-4-ium-4
      methoxyphenyl [morpholino] phosphinodithioate) induced stomatal closure, which
      peaked after 150 min at 1 uM or after 90 min at 10 and 100 uM. After reaching
      maximal closure, stomatal apertures gradually increased in size in response to
      further exposure to GYY4137. GYY4137 induced nitric oxide (NO) generation in
      guard cells, and GYY4137-induced stomatal closure was reduced by an NO scavenger
      and inhibitors of NO-producing enzymes. Mass spectrometry analyses showed that
      GYY4137 induces the synthesis of 8-nitro-cGMP and 8-mercapto-cGMP and that this
      synthesis is mediated by NO. In addition, 8-mercapto-cGMP triggered stomatal
      closure. Moreover, inhibitor and genetic studies showed that calcium, cADP ribose
      and slow anion channel 1 act downstream of 8-mercapto-cGMP. This study therefore
      demonstrates that 8-mercapto-cGMP mediates the H2S signaling cascade in guard
      cells. 

PMID- 25975265
TI  - Persistent complete remission of acute leukemic-phase CCR4-positive gamma-delta
      peripheral T-cell lymphoma by autologous stem cell transplantation with
      mogamulizumab.
AB  - Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), frequently shows
      a poor outcome. Especially, expressions of CC chemokine receptor 4 (CCR4) and
      gammadelta T-cell receptor (TCR) are associated with worse prognosis in PTCL-NOS.
      We here report successful treatment with autologous peripheral blood stem cell
      transplantation (auto-PBSCT) combined with anti-CCR4 antibody mogamulizumab for a
      very rare case of CCR4+gammadeltaTCR+ PTCL-NOS that coexisted with Hodgkin's
      lymphoma. PTCL-NOS in this patient progressed to leukemic phase, whereas
      Hodgkin's lymphoma disappeared with standard chemotherapies within 4 years of the
      initial diagnosis. Leukemic-phase PTCL-NOS was refractory to several
      chemotherapies. However, auto-PBSCT following high-dose chemotherapy combined
      with pre- and post-transplant mogamulizumab, which is a humanized monoclonal
      antibody to CCR4, provided persistent complete remission of PTCL-NOS, despite
      residual gammadeltaTCR+ in the transplanted stem cell product, suggesting a
      purging effect of mogamulizumab. At 15 months after transplantation, we also
      found markedly fewer effector regulatory T cells, which may have contributed to
      prolonged remission. This case suggests that autologous stem cell transplantation
      combined with mogamulizumab may have a potential to cure T-cell neoplasms that
      express CCR4 including leukemic-phase PTCL-NOS.

PMID- 25975266
TI  - Adherence to the Mediterranean diet and academic performance in youth: the
      UP&DOWN study.
AB  - PURPOSE: To examine the association between adherence to the Mediterranean diet
      and academic performance in children and adolescents. METHODS: This is a cross
      sectional study conducted with 1371 youth aged 12.04 +/- 2.50 years (685 girls)
      in Spain during 2011-2012. Adherence to the Mediterranean diet was assessed using
      the KIDMED index (Mediterranean Diet Quality Index in children and adolescents),
      which includes 16 questions on specific dietary patterns. Levels of adherence
      were classified into three groups: poor adherence (0-3), average adherence (4-7),
      and good adherence (8-12). Academic performance was assessed through school
      records using four indicators: math, language, an average of math and language,
      and grade point average score. RESULTS: Adherence to the Mediterranean diet was
      related to academic performance (beta ranging from 0.107 to 0.148; all P < 0.001)
      after adjusting for confounders. The group of good adherence to the Mediterranean
      diet had significantly higher scores in all of the academic indicators compared
      with the poor group (ranging from +0.429 to 0.464; all P <= 0.001); as well as
      the group of average adherence to the Mediterranean diet had significantly higher
      scores in all of the academic indicators compared with the poor group (ranging
      from +0.292 to 0.344; all P <= 0.06). There were no differences between the
      groups of good and average adherence to the Mediterranean diet. CONCLUSIONS:
      Adherence to the Mediterranean diet may have a beneficial influence on academic
      performance in youth. Importantly, the benefits of adherence to the Mediterranean
      diet on academic performance may be stronger as youth adhered to the optimal
      Mediterranean diet levels.

PMID- 25975267
TI  - Disease Extension Matters in Endoscopic Scores: UCEIS Calculated as a Sum of the
      Single Colonic Segments Performed Better than Regular UCEIS in Outpatients with
      Ulcerative Colitis.

PMID- 25975268
TI  - Heavy Metal Ion Regulation of Gene Expression: MECHANISMS BY WHICH LEAD INHIBITS
      OSTEOBLASTIC BONE-FORMING ACTIVITY THROUGH MODULATION OF THE Wnt/beta-CATENIN
      SIGNALING PATHWAY.
AB  - Exposure to lead (Pb) from environmental sources remains an overlooked and
      serious public health risk. Starting in childhood, Pb in the skeleton can disrupt
      epiphyseal plate function, constrain the growth of long bones, and prevent
      attainment of a high peak bone mass, all of which will increase susceptibility to
      osteoporosis later in life. We hypothesize that the effects of Pb on bone mass,
      in part, come from depression of Wnt/beta-catenin signaling, a critical anabolic
      pathway for osteoblastic bone formation. In this study, we show that depression
      of Wnt signaling by Pb is due to increased sclerostin levels in vitro and in
      vivo. Downstream activation of the beta-catenin pathway using a pharmacological
      inhibitor of GSK-3beta ameliorates the Pb inhibition of Wnt signaling activity in
      the TOPGAL reporter mouse. The effect of Pb was determined to be dependent on
      sclerostin expression through use of the SOST gene knock-out mice, which are
      resistant to Pb-induced trabecular bone loss and maintain their mechanical bone
      strength. Moreover, isolated bone marrow cells from the sclerostin null mice show
      improved bone formation potential even after exposure to Pb. Also, our data
      suggest that the TGFbeta canonical signaling pathway is the mechanism by which Pb
      controls sclerostin production. Taken together these results support our
      hypothesis that the osteoporotic-like phenotype observed after Pb exposure is, in
      part, regulated through modulation of the Wnt/beta-catenin pathway. 

PMID- 25975269
TI  - Mechanistic Aspects of Folded Protein Transport by the Twin Arginine Translocase
      (Tat).
AB  - The twin arginine translocase (Tat) transports folded proteins of widely varying
      size across ionically tight membranes with only 2-3 components of machinery and
      the proton motive force. Tat operates by a cycle in which the receptor complex
      combines with the pore-forming component to assemble a new translocase for each
      substrate. Recent data on component and substrate organization in the receptor
      complex and on the structure of the pore complex inform models for translocase
      assembly and translocation. A translocation mechanism involving local transient
      bilayer rupture is discussed. 

PMID- 25975270
TI  - Loss of the Mono-ADP-ribosyltransferase, Tiparp, Increases Sensitivity to Dioxin
      induced Steatohepatitis and Lethality.
AB  - The aryl hydrocarbon receptor (AHR) mediates the toxic effects of the
      environmental contaminant dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD).
      Dioxin causes a range of toxic responses, including hepatic damage,
      steatohepatitis, and a lethal wasting syndrome; however, the mechanisms are still
      unknown. Here, we show that the loss of TCDD-inducible poly(ADP-ribose)
      polymerase (Tiparp), an ADP-ribosyltransferase and AHR repressor, increases
      sensitivity to dioxin-induced toxicity, steatohepatitis, and lethality. Tiparp(-/
      ) mice given a single injection of 100 MUg/kg dioxin did not survive beyond day
      5; all Tiparp(+/+) mice survived the 30-day treatment. Dioxin-treated Tiparp(-/-)
      mice exhibited increased liver steatosis and hepatotoxicity. Tiparp ADP
      ribosylated AHR but not its dimerization partner, the AHR nuclear translocator,
      and the repressive effects of TIPARP on AHR were reversed by the macrodomain
      containing mono-ADP-ribosylase MACROD1 but not MACROD2. These results reveal
      previously unidentified roles for Tiparp, MacroD1, and ADP-ribosylation in AHR
      mediated steatohepatitis and lethality in response to dioxin. 

PMID- 25975271
TI  - Cytochrome P450 in living donor liver transplantation.
AB  - Cytochrome P450 metabolizes many drugs in the liver. Three genotypes of CYP2C19
      with extensive, intermediate, and poor metabolizing activity, respectively, have
      been identified in peripheral blood of transplant recipients and new liver grafts
      in living donor liver transplantation (LDLT). The expression of the final
      genotype in liver graft biopsies depends on the donor, whereas the expression in
      peripheral blood mononuclear cells depends on the recipient. The metabolizing
      isoenzyme of the major anti-rejection agents passes through CYP3A4, CYP3A5 and
      MDR1, which have also been identified to have similar biological characteristics
      as genotype of CYP2C19 in liver tissue. Recently, pyrosequencing has been used to
      investigate the expressions of different genotypes in liver grafts in LDLT. This
      review focuses on recent findings regarding the biological expressions of the
      CYP2C19, CYP3A4, CYP3A5 and MRD1 genotypes in liver grafts before and after LDLT.
      The application of pyrosequencing may be beneficial in further research on liver
      transplantation. Laser capture microdissection of hepatocytes in liver grafts may
      be a direction for future research. 

PMID- 25975272
TI  - Effects of etidronate on the Enpp1-/- mouse model of generalized arterial
      calcification of infancy.
AB  - Generalized arterial calcification of infancy (GACI) is an autosomal recessive
      disorder of spontaneous infantile arterial and periarticular calcification which
      is attributed to mutations in the ectonucleotide
      pyrophosphatase/phosphodiesterase 1 (Enpp1) gene. Whilst the bisphosphonate,
      etidronate, is currently used off-label for the treatment for GACI, recent
      studies have highlighted its detrimental effects on bone mineralisation. In the
      present study, we used the Enpp1-/- mouse model of GACI to examine the effects of
      etidronate treatment (100 ug/kg), on vascular and skeletal calcification. Micro
      computed tomography (uCT) analysis revealed a significant decrease in trabecular
      bone mass, as reflected by the decrease in trabecular bone volume/tissue volume
      (BV/TV; %), trabecular thickness, trabecular separation, trabecular number and
      pattern factor (P<0.05) in the Enpp1-/- mice in comparison to the wild-type (WT)
      mice. Mechanical testing revealed that in the WT mice, treatment with etidronate
      significantly improved work to fracture and increased work post-failure (P<0.05,
      in comparison to the vehicle-treated WT mice). This significant increase,
      however, was not observed in the Enpp1-/- mice. Treatment with etidronate had no
      effect on bone parameters in the WT mice; however, the Enpp1-/- mice displayed an
      increased structural model index (SMI; P<0.05). We used a recently developed 3D
      uCT protocol to reconstruct and quantify the extensive aortic calcification in
      Enpp1-/- mice in comparison to the WT mice. However, treatment with etidronate
      did not prevent de novo calcification, and did not arrest the progression of
      established calcification of the aorta.

PMID- 25975274
TI  - Validation of the Spanish version of the Multidimensional State Boredom Scale
      (MSBS).
AB  - BACKGROUND: Boredom, which is a common problem in the general population, has
      been associated with several psychiatric disorders. The Multidimensional State
      Boredom Scale (MSBS) was developed, based on a theoretically and empirically
      grounded definition of boredom, to assess this construct. The aim of the present
      study was to assess the psychometric properties of the Spanish validated version
      of the MSBS in a multi-age sample recruited from the general population. METHODS:
      The patients (N = 303) were recruited from primary care settings. In addition to
      the sociodemographic variables and the MSBS, the General Health Questionnaire 28
      items (GHQ-28), Positive and Negative Affect Scale (PANAS), Negative subscale and
      the Mindful Attention Awareness Scale (MAAS) were administered. We used
      confirmatory factor analysis (CFA) to analyse the dimensionality of the MSBS.
      Cronbach's alpha coefficient was used to analyse the internal consistency of the
      scale. The consistency of the MSBS over time (test-retest reliability) was
      assessed using the intra-class correlation coefficient. The construct validity
      was examined by calculating Pearson's r correlations between the MSBS with
      theoretically related and unrelated constructs. Cronbach's alpha for MSBS was
      0.89 (95 % CI, 0.87-0.92), ranging from 0.75 to 0.83 for the 5 subscales.
      RESULTS: The characteristics of the final sample (N = 303) were that the
      participants were primarily female (66.77 %) with a mean age of 49.32 years (SD,
      11.46) and primarily European (94.71 %). The CFA of the MSBS confirmed that the
      original five-factor model showed good fit indices: CFI = .96; GFI = .94; SRMR =
      .05; and RMSEA = .06 [.05-.08]. Cronbach's alpha for MSBS was 0.89 (95 % CI, 0.87
      0.92), ranging from 0.75 to 0.83 for the 5 subscales. The MSBS showed a test
      retest coefficient measured with an ICC of 0.90 (95 % CI, 0.88-0.92). The ICC for
      the 5 subscales ranged from 0.81 to 0.89. The MSBS showed a significant negative
      correlation with MAAS and a significant positive correlation with the GHQ (total
      score and subscales) and PANAS-Negative Affect. CONCLUSIONS: The Spanish version
      of the MSBS has been validated as a reliable instrument for measuring boredom in
      the general population. This study will facilitate the assessment of boredom for
      clinical and research purposes in Spanish-speaking populations.

PMID- 25975273
TI  - Autoantibodies in breast cancer sera are not epiphenomena and may participate in
      carcinogenesis.
AB  - BACKGROUND: The objective of this work was to demonstrate that autoantibodies in
      breast cancer sera are not epiphenomena, and exhibit unique immunologic features
      resembling the rheumatic autoimmune diseases. METHODS: We performed a
      comprehensive study of autoantibodies on a collection of sera from women with
      breast cancer or benign breast disease, undergoing annual screening mammography.
      All women in this study had suspicious mammography assessment and underwent a
      breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti
      dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. RESULTS:
      Autoantibodies were detected in virtually all patients with breast cancer,
      predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast
      cancer sera showed distinctive features, such as antibodies targeting
      mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple
      nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not
      react with the M2 component of pyruvate dehydrogenase, characteristic of primary
      biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for
      extractable nuclear antigens and the assays for dsDNA were negative. CONCLUSIONS:
      The distinctive autoantibody profile detected in BC sera is the expression of
      tumor immunogenicity. Although some of these features resemble those in the
      rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the
      involvement of an entirely different set of epithelial antigens in breast cancer.
      High titer autoantibodies targeting centrosomes, centromeres, and mitochondria
      were detected in a small group of healthy women with suspicious mammography
      assessment and no cancer by biopsy; this suggests that the process triggering
      autoantibody formation starts in the pre-malignant phase and that future studies
      using validated autoantibody panels may allow detection of breast cancer risk in
      asymptomatic women. Autoantibodies developing in breast cancer are not
      epiphenomena, but likely reflect an antigen-driven autoimmune response triggered
      by epitopes developing in the mammary gland during breast carcinogenesis. Our
      results support the validity of the multiple studies reporting association of
      autoantibodies with breast cancer. Results further suggest significant promise
      for the development of panels of breast cancer-specific, premalignant-phase
      autoantibodies, as well as studies on the autoantibody response to tumor
      associated antigens in the pathogenesis of cancer.

PMID- 25975276
TI  - Hyperthermia-related clinical trials on cancer treatment within the
      ClinicalTrials.gov registry.
AB  - PURPOSE: Hyperthermia has been shown to improve the effectiveness of chemotherapy
      and radiotherapy in the treatment of cancer. This paper summarises all recent
      clinical trials registered in the ClinicalTrials.gov registry. MATERIALS AND
      METHODS: The records of 175,538 clinical trials registered at ClinicalTrials.gov
      were downloaded on 29 September 2014 and a database was established. We searched
      this database for hyperthermia or equivalent words. RESULTS: A total of 109
      trials were identified in which hyperthermia was part of the treatment regimen.
      Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after
      cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials
      (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion.
      Seven trials (6%) were testing perfusion attempts to other locations
      (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were
      testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven
      trials (6%) superficial hyperthermia and two trials (2%) interstitial
      hyperthermia. One remaining trial tested laser hyperthermia. CONCLUSIONS: In
      contrast to the general opinion, this analysis shows continuous interest and
      ongoing clinical research in the field of hyperthermia. Interestingly, the
      majority of trials focused on some form of intraperitoneal hyperthermic
      chemoperfusion. Despite the high number of active clinical studies, HIPEC is a
      topic with limited attention at the annual meetings of the European Society for
      Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on
      going clinical trials is of paramount importance for the achievement of a
      comprehensive overview of available clinical research activities involving
      hyperthermia.

PMID- 25975275
TI  - Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat:
      A Review.
AB  - Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world.
      The vast majority of CRC cases have been linked to environmental causes rather
      than to heritable genetic changes. Over the last decades, epidemiological
      evidence linking the consumption of red and, more convincingly, of processed red
      meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms
      underlying an association between CRC and the intake of red and processed red
      meat have been proposed and investigated in biological studies. The hypotheses
      that have received most attention until now include (1) the presence of
      polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of
      compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme
      on the formation of carcinogenic N-nitroso compounds and lipid peroxidation.
      However, none of these hypotheses completely explains the link between red and
      processed red meat intake and the CRC risk. Consequently, scientists have
      proposed additional mechanisms or refined their hypotheses. This review first
      briefly summarizes the development of CRC followed by an in-depth overview and
      critical discussion of the different potential carcinogenic mechanisms underlying
      the increased CRC risk associated with the consumption of red and processed red
      meat. 

PMID- 25975277
TI  - Albumin in nephrotic syndrome and oedematous malnutrition.

PMID- 25975278
TI  - Pattern of childhood cancer in University College Hospital, Ibadan during 1991
      2010 and comparison with the previous three decades.
AB  - BACKGROUND: Cancer is an important cause of morbidity and mortality worldwide in
      children under 15 years of age, with the incidence and mortality rate varying
      from 40 to 155 per million children. AIM: To describe the pattern of childhood
      cancer in Ibadan, Nigeria. OBJECTIVE: To compare the findings of this study with
      those of previous studies in Ibadan and internationally. METHODS: A retrospective
      review of histologically and cytologically confirmed cases of cancer in children
      aged <15 years diagnosed at University College Hospital (UCH), Ibadan between
      January 1991 and December 2010 was undertaken. The cases were categorised using
      the International Classification of Childhood Cancer, third edition (ICCC-3).
      RESULTS: There were 625 cases comprising 360 (57.6%) males with a modal age of 3
      years. The most common neoplasms were lymphomas (140, 22.4%), of which 90% were
      non-Hodgkin lymphomas, with Burkitt lymphoma constituting the majority of cases
      (73). Other common neoplasms were retinoblastomas (21%), soft tissue sarcomas
      (14.9%), leukaemias (10.2%) and CNS tumours (6.9%). Lymphomas, bone tumours,
      malignant hepatic tumours and other malignant epithelial neoplasms had the
      highest mean and modal ages, while retinoblastomas, neuroblastomas, germ cell
      tumours and renal tumours had the lowest mean and modal ages. During 1960-72
      there were 1326 cases and during 1973-90 there were 1881 cases and the proportion
      of lymphomas was 58.9% and 45.4%, respectively. The present study demonstrated a
      marked decline in the number of cases and proportion of lymphomas (22.4%),
      particularly Burkitt lymphomas. CONCLUSION: During the last 20 years, there has
      been a decline in the number of cases of childhood cancer seen at UCH, Ibadan.
      This may be due to the establishment of additional specialist centres in the sub
      region. Owing to a persistent decline in the frequency of Burkitt lymphoma,
      retinoblastoma is now the most common individual childhood cancer seen at Ibadan.

PMID- 25975279
TI  - Letter to the editor. Defence of my hypothesis that the oedema of kwashiorkor is
      caused by hypoalbuminaemia.

PMID- 25975280
TI  - Low affinity binding of plasma proteins to lipid-coated quantum dots as observed
      by in situ fluorescence correlation spectroscopy.
AB  - Protein binding to lipid-coated nanoparticles has been pursued quantitatively by
      using fluorescence correlation spectroscopy. The binding of three important
      plasma proteins to lipid-enwrapped quantum dots (QDs) shows very low affinity,
      with an apparent dissociation coefficient in the range of several hundred
      micromolar. Thus, the tendency to adsorb is orders of magnitude weaker than for
      QDs coated with dihydrolipoic acid. 

PMID- 25975281
TI  - Ion intercalation dynamics of electrosynthesized mesoporous WO3 thin films
      studied by multi-scale coupled electrogravimetric methods.
AB  - Mesoporous WO3 thin films were prepared electrochemically by using an ionic
      surfactant during the synthesis, and the electrochemical properties are
      investigated in comparison with their dense analogues. This report specifically
      highlights the suitability of a time resolved coupled electrogravimetric method
      to follow meticulously the ion intercalation/extraction phenomena which revealed
      the enhanced ion intercalation/extraction behavior of electrodeposited mesoporous
      WO3 thin films for diverse applications in energy storage and electrochromism.
      This methodology (electrochemical impedance spectroscopy (EIS) and its coupling
      with a fast quartz crystal microbalance (QCM)) has the ability to detect the
      contribution of the charged or uncharged species during the electrochemical
      processes, and to deconvolute the global EQCM responses into the anionic,
      cationic, and the free solvent contributions. Our study identifies the
      involvement of several charged species (Li(+), Li(+).H2O) in the compensation of
      charge, and H2O molecules indirectly contribute to the process in both dense and
      mesoporous WO3 thin films. Even a slight contribution of ClO4(-) ions was
      detected in the case of mesoporous analogues. The results of the study indicate
      that the transfer resistances of Li(+) and Li(+).H2O are decreased when the WO3
      films are mesoporous. A more significant difference is observed for the larger
      and partially dehydrated Li(+).H2O ions, suggesting that increased surface area
      and pore volume created by mesoporous morphology facilitate the transfer of
      larger charged species. The relative concentration changes of cations are also
      magnified in the mesoporous films. The final concentration variations are higher
      in mesoporous films than that in the dense analogues; ~4 times and ~10 times
      higher for Li(+) and for Li(+).H2O, respectively. To the best of our knowledge,
      an unambiguous identification of species other than desolvated cations (e.g.
      Li(+) ions), the information on their transfer dynamics and quantification of the
      transferred species have never been reported in the literature to describe the
      charge compensation process in WO3 based electrodes. 

PMID- 25975282
TI  - Impact of land use type conversion on carbon storage in terrestrial ecosystems of
      China: A spatial-temporal perspective.
AB  - Our work is the first study to explore the national and provincial composite
      carbon storage variations in terrestrial ecosystems of China caused by the entire
      flows of land use type conversion (LUTC). Only water body was excluded. The
      results indicated that terrestrial ecosystems of China lost 219 Tg-C due to LUTC
      from 1980 to 1995, and the amount was 60 Tg-C during the period 1995-2010.
      Despite the decrease in the total amount, carbon losses from LUTC intensified,
      but most of the losses were balanced by the opposite conversions. Our analyses
      also revealed that LUTCs in China were becoming detrimental to carbon reduction,
      mainly due to the insufficient increase of forest land to meet the growing demand
      for carbon absorption, the accelerating disappearance of grassland and the rapid
      expansion of settlements. More than 50% of the carbon storage variations for a
      single LUTC flow concentrated in several provinces. To improve China's LUTC
      status from the aspect of low-carbon, Heilongjiang, Sichuan, Inner Mongolia,
      Tibet, Qinghai, Xinjiang and coastal regions, such as Shandong, Jiangsu and
      Liaoning, should be dealt with first according to their conditions. This study
      can be helpful to planners, policy makers and scholars concerned about carbon
      reduction in China. 

PMID- 25975283
TI  - Realization of a micrometre-scale spin-wave interferometer.
AB  - The recent development of spin dynamics opens perspectives for various
      applications based on spin waves, including logic devices. The first important
      step in the realization of spin-wave-based logics is the manipulation of spin
      wave interference. Here, we present the experimental realization of a micrometre
      scale spin-wave interferometer consisting of two parallel spin-wave waveguides.
      The spin waves propagate through the waveguides and the superposition or
      interference of the electrical signals corresponding to the spin waves is
      measured. A direct current flowing through a metal wire underneath one of the
      spin-wave waveguides affects the propagation properties of the corresponding spin
      wave. The signal of constructive or destructive interference depends on the
      magnitude and direction of the applied direct current. Thus, the present work
      demonstrates a unique manipulation of spin-wave interference. 

PMID- 25975284
TI  - Sequencing of 279 cancer genes in ampullary carcinoma reveals trends relating to
      histologic subtypes and frequent amplification and overexpression of ERBB2
      (HER2).
AB  - The biological relevance of histological subtyping of ampullary carcinoma into
      intestinal vs pancreaticobiliary types remains to be determined. In an effort to
      molecularly profile these subtypes of ampullary carcinomas, we conducted a two
      phase study. In the discovery phase, we identified 18 pancreatobiliary-type
      ampullary carcinomas and 14 intestinal-type ampullary carcinomas using stringent
      pathologic criteria and performed next-generation sequencing targeting 279 cancer
      associated genes on these tumors. Although the results showed overlapping of
      genomic alterations between the two subtypes, trends including more frequent KRAS
      alterations in pancreatobiliary-type ampullary carcinoma (61 vs 29%) and more
      frequent mutations in APC in intestinal-type ampullary carcinoma (43 vs 17%) were
      observed. Of the entire cohort of 32 tumors, the most frequently mutated gene was
      TP53 (n=17); the most frequently amplified gene was ERBB2 (n=5); and the most
      frequently deleted gene was CDKN2A (n=6). In the second phase of the study, we
      aimed at validating our observation on ERBB2 and assessed ERBB2 amplification and
      protein overexpression in a series of 100 ampullary carcinomas. We found that (1)
      gene amplification and immunohistochemical overexpression of ERBB2 occurred in
      13% of all ampullary carcinomas, therefore providing a potential target for anti
      HER2 therapy in these tumors; (2) amplification and immunohistochemical
      expression correlated in all cases, thus indicating that immunohistochemistry
      could be used to screen tumors; and (3) none of the 14 ERBB2-amplified tumors
      harbored any downstream driver mutations in KRAS/NRAS, whereas 56% of the cases
      negative for ERBB2 amplification did, an observation clinically pertinent as
      downstream mutations may cause primary resistance to inhibition of EGFR family
      members. 

PMID- 25975285
TI  - Reproducibility and prognostic significance of morphologic dysplasia in de novo
      acute myeloid leukemia.
AB  - The 2008 WHO classification of acute myeloid leukemia includes a category of
      acute myeloid leukemia with myelodysplasia-related changes; however, the
      significance of multilineage dysplasia alone is controversial and its
      reproducibility has not been evaluated in acute myeloid leukemia. We performed an
      in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia
      cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008
      WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%)
      and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27
      cases were ambiguous as to myelodysplasia-related changes status due to limited
      maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable
      analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor
      acute myeloid leukemia-not evaluable showed significantly different event-free
      survival compared with acute myeloid leukemia-not otherwise specified in the 137
      patients treated with induction chemotherapy. When individual dysplastic features
      were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged
      as factors significantly associated with shorter event-free survival in a
      multivariable analysis that included the other significant covariates of age,
      white blood count, platelet count, abnormal karyotype and stem-cell
      transplantation. Our findings indicate that the current 2008 WHO definition of
      multilineage dysplasia in acute myeloid leukemia in its current form is not
      optimal, and that the use of a more restricted definition of morphologic
      dysplasia results in more relevant risk stratification that is independent of
      other conventional prognostic factors. 

PMID- 25975286
TI  - Microanatomy of the cervical and anorectal squamocolumnar junctions: a proposed
      model for anatomical differences in HPV-related cancer risk.
AB  - Human papilloma virus (HPV) infection causes cancers and their precursors (high
      grade squamous intraepithelial lesions) near cervical and anal squamocolumnar
      junctions. Recently described cervical squamocolumnar junction cells are putative
      residual embryonic cells near the cervical transformation zone. These cells
      appear multipotential and share an identical immunophenotype (strongly CK7
      positive) with over 90% of high-grade squamous intraepithelial lesions and
      cervical carcinomas. However, because the number of new cervical cancers
      discovered yearly world wide is 17-fold that of anal cancer, we posed the
      hypothesis that this difference in cancer risk reflects differences in the
      transition zones at the two sites. The microanatomy of the normal anal
      transformation zone (n=37) and topography and immunophenotype of anal squamous
      neoplasms (n=97) were studied. A discrete anal transition zone was composed of
      multilayered CK7-positive/p63-negative superficial columnar cells and an
      uninterrupted layer of CK7-negative/p63-positive basal cells. The CK7
      negative/p63-positive basal cells were continuous with-and identical in
      appearance to-the basal cells of the mature squamous epithelium. This was in
      contrast to the cervical squamocolumnar junction, which harbored a single-layered
      CK7-positive/p63-negative squamocolumnar junction cell population. Of the 97 anal
      intraepithelial neoplasia/squamous cell carcinomas evaluated, only 27% (26/97)
      appeared to originate near the anal transition zone and only 23% (22/97) were CK7
      positive. This study thus reveals two fundamental differences between the anus
      and the cervix: (1) the anal transition zone does not harbor a single monolayer
      of residual undifferentiated embryonic cells and (2) the dominant tumor
      immunophenotype is in keeping with an origin in metaplastic (CK7-negative)
      squamous rather than squamocolumnar junction (CK7-positive) epithelium. The
      implication is that, at birth, the embryonic cells in the anal transition zone
      have already begun to differentiate, presenting a metaplasia that-similar to
      vaginal and vulvar epithelium-is less prone to HPV-directed carcinogenesis. This
      in turn underscores the link between cancer risk and a very small and discrete
      population of vulnerable squamocolumnar junction cells in the cervix. 

PMID- 25975287
TI  - PDGFRA-mutant syndrome.
AB  - Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal
      mesenchymal tumors. In its familial form this disease, which was formerly termed
      intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included
      among familial gastrointestinal stromal tumors (GISTs) because of its genotype,
      described when GIST was the only known PDGFRA-mutant gastrointestinal tumor.
      Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA
      mutations. Subsequently, gastrointestinal CD34+ 'fibrous tumors' of uncertain
      classification were described in a germline PDGFRA-mutant context. Our aim was to
      characterize the syndrome produced by germline PDGFRA mutations and establish
      diagnostic criteria and management strategies for this hitherto puzzling disease.
      We studied a kindred displaying multiple gastrointestinal mesenchymal tumors,
      comparing it with published families/individuals with possible analogous
      conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting
      the third reported example of familial PDGFRA mutation. In adult mutants we
      detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous
      tumors of uncertain nosology. We demonstrate that the syndrome formerly defined
      as INF/NF3b (exemplified by the family reported herein) is simplistically
      considered a form of familial GIST, because inflammatory fibroid polyps often
      prevail. Fibrous tumors appear variants of inflammatory fibroid polyps.
      'INF/NF3b' and 'familial GIST' are misleading terms which we propose changing to
      'PDGFRA-mutant syndrome'. In this condition, unlike KIT-dependent familial GIST
      syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell
      hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA
      mutant syndrome: (i) focuses oncological concern on gastric masses, as
      inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric
      environment for PDGFRA mutations to elicit GISTs, justifying the known
      predilection for stomach of sporadic PDGFRA-mutant GISTs. An awareness that
      inflammatory fibroid polyps, relatively common among gastrointestinal mesenchymal
      tumors, may be the prevailing tumor in PDGFRA-mutant syndrome could eventually
      reveal an unsuspected prevalence of this condition. 

PMID- 25975288
TI  - Future opportunities in preventing ototoxicity: Caffeic acid phenethyl ester may
      be a candidate (Review).
AB  - Caffeic acid phenethyl ester (CAPE) is an important active component of propolis,
      which is derived from honeybee hives. It has received increasing attention in a
      variety of medical and pharmaceutical research, due to its anti-oxidant,
      antiproliferative, anti-inflammatory, antiviral and antifungal activity, in
      addition to its antineoplastic properties. Besides the use of CAPE as an
      antioxidant and anti-inflammatory agent in a number of in vivo studies of ear
      disease, its beneficial effects have been reported in the treatment of cancer,
      arthritis, allergies, heart disease, diabetes, kidney disease, liver disease and
      neurological disease. CAPE influences a number of biochemical pathways, as well
      as several targets involved in ear diseases, in particular, in ototoxicity. The
      protective effects of CAPE in ototoxicity, which may be induced by a number
      factors, including lipopolysaccharides, hydrogen peroxide and streptomycin, are
      evaluated and discussed in the present review. 

PMID- 25975289
TI  - Effects of Preretirement Work Complexity and Postretirement Leisure Activity on
      Cognitive Aging.
AB  - OBJECTIVES: We examined the influence of postretirement leisure activity on
      longitudinal associations between work complexity in main lifetime occupation and
      trajectories of cognitive change before and after retirement. METHODS:
      Information on complexity of work with data, people, and things, leisure activity
      participation in older adulthood, and four cognitive factors (verbal, spatial,
      memory, and speed) was available from 421 individuals in the longitudinal Swedish
      Adoption/Twin Study of Aging. Participants were followed for an average of 14.2
      years (SD = 7.1 years) and up to 23 years across eight cognitive assessments.
      Most of the sample (88.6%) completed at least three cognitive assessments.
      RESULTS: Results of growth curve analyses indicated that higher complexity of
      work with people significantly attenuated cognitive aging in verbal skills,
      memory, and speed of processing controlling for age, sex, and education. When
      leisure activity was added, greater cognitive and physical leisure activity was
      associated with reduced cognitive aging in verbal skills, speed of processing,
      and memory (for cognitive activity only). DISCUSSION: Engagement in cognitive or
      physical leisure activities in older adulthood may compensate for cognitive
      disadvantage potentially imposed by working in occupations that offer fewer
      cognitive challenges. These results may provide a platform to encourage leisure
      activity participation in those retiring from less complex occupations.

PMID- 25975291
TI  - JGPS Special Series on Race, Ethnicity, Life Experiences, and Cognitive Aging.

PMID- 25975290
TI  - Childhood Conditions and Multimorbidity Among Older Adults.
AB  - OBJECTIVES: This research tests whether childhood conditions are associated with
      trajectories of chronic conditions among older adults. METHODS: Using data from
      the Health and Retirement Study (1992-2008), a series of hierarchical linear
      models are used to estimate number of chronic conditions at survey midpoint and
      the rate of increase in chronic conditions across 18 years of data. RESULTS:
      Results suggest that lower childhood socioeconomic status (SES) and poor
      childhood health are associated with increased number of chronic conditions;
      however, childhood SES is no longer associated with chronic conditions after
      adjustment for adult SES and adult health. Poor childhood health continues to be
      associated with total number of chronic conditions after adjustment for adult SES
      and health. Rate of change in chronic conditions was not associated with
      childhood conditions. Results from a multinomial logistic regression model
      further indicated that the association between childhood conditions and adult
      multimorbidity increased at higher levels of multimorbidity. DISCUSSION: This
      research adds to the evidence that early life conditions have a lasting influence
      on adult health, and that their influence may be independent of adult health and
      SES.

PMID- 25975292
TI  - A Role for Identification in the Gradual Decline in the Pleasantness of Flavors
      With Age.
AB  - OBJECTIVES: This study investigated a possible role for identification in the
      decline in flavor pleasantness with age. METHODS: Two hundred sixty-four
      individuals aged from 16 to 85 years tasted 6 flavored drinks of varying identity
      and ease of identification, and rated each on pleasantness, a range of other
      characteristics and identified all flavors. RESULTS: Using regression, firstly,
      pleasantness was inversely associated with age (beta = -0.22, p < .01). Secondly,
      the decline in pleasantness with age was associated with poorer identification
      (beta = 0.30, p < .01), lower perceptions of sweetness (beta = 0.01, p < .01),
      lower strength of flavor (beta = 0.00, p = .02), lower familiarity (beta = 0.01,
      p < .01), and a lower frequency of usual drink consumption (beta = 0.04, p <
      .01). Thirdly, improved identification with age was associated with increased
      drink familiarity (beta =< 0.01, p < .01), coloration compared with no color
      (beta = <0.06, p < .01), and correct compared with incorrect coloration (beta =
      <0.27, p < .01). DISCUSSION: These findings demonstrate a clear role for
      identification in the decline in flavor pleasantness with age. These findings
      thus provide clear evidence for a cognitive and perceptual element to these
      hedonic processes. Our findings suggest that likings for flavors in older
      individuals may be increased/maintained through the use of improved visual cues,
      easily recognizable foods, and/or identity labels.

PMID- 25975294
TI  - [Expert Consensus for Image-guided Radiofrequency Ablation of Pulmonary Tumors].

PMID- 25975295
TI  - [Methylation Status of miR-182 Promoter in Lung Cancer Cell Lines].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that the abnormal expression of miR
      182 was related to the occurrence and development of tumors. The aim of this
      study is to explore the relationship between the methylation of miR-182 promoter
      and its expression in lung cancer cell lines. METHODS: Real-time quantitative PCR
      and methylation-specific PCR were used to detect the expression level of miR-182
      and its promoter methylation status in five lung cancer cell lines (A549, L9981,
      NL9980, 95C and 95D). DNA sequencing was used to confirm the methylation results.
      RESULTS: The level of miR-182 expression significantly differs among these lung
      cancer cell lines. The highly metastatic human lung cancer cell lines, namely,
      A549 and L9981, demonstrate a relatively lower expression level of miR-182
      compared with the lowly metastatic human lung cancer cell line 95C. Methylation
      specific PCR and DNA sequencing assay results indicate that these lung cancer
      cell lines present different levels of miR-182 promoter methylation, and the
      highest methylation level is observed in A549 cells. Furthermore, the expression
      of miR-182 in these cell lines significantly increases when treated with 10 MUM
      5'-Aza-dC. CONCLUSIONS: DNA methylation occurs in the miR-182 promoter region in
      lung cancer cell lines. This methylation can regulate the expression level of miR
      182. Further study must be conducted to explore the function of miR-182 promoter
      methylation in lung cancer occurrence and development.?.

PMID- 25975293
TI  - Memory for Allergies and Health Foods: How Younger and Older Adults Strategically
      Remember Critical Health Information.
AB  - OBJECTIVES: While older adults often display memory deficits, with practice, they
      can sometimes selectively remember valuable information at the expense of less
      value information. We examined age-related differences and similarities in memory
      for health-related information under conditions where some information was
      critical to remember. METHOD: In Experiment 1, participants studied 3 lists of
      allergens, ranging in severity from 0 (not a health risk) to 10 (potentially
      fatal), with the instruction that it was particularly important to remember items
      to which a fictional relative was most severely allergic. After each list,
      participants received feedback regarding their recall of the high-value
      allergens. Experiment 2 examined memory for health benefits, presenting foods
      that were potentially beneficial to the relative's immune system. RESULTS: While
      younger adults exhibited better overall memory for the allergens, both age groups
      in Experiment 1 developed improved selectivity across the lists, with no evident
      age differences in severe allergen recall by List 2. Selectivity also developed
      in Experiment 2, although age differences for items of high health benefit were
      present. DISCUSSION: The results have implications for models of selective memory
      in older age, and for how aging influences the ability to strategically remember
      important information within health-related contexts.

PMID- 25975296
TI  - [Therapeutical effects of pleural injecting recombinant human endostain to
      ?malignant pleural effusion nude mice model].
AB  - BACKGROUND AND OBJECTIVE: The prognosis of malignant pleural effusion (MPE) was
      poor, injecting anti-angiogenesis agents in pleural cavity might be to reducing
      the volume of pleural effusion. The aim of this study is to investigate the
      therapeutical effect of pleural injection of recombinant human endostain,
      cisplatin and recombinant human endostain combined with cisplatin to MPE nude
      mice. METHODS: MPE model was built by intrpleural injection of Lewis lung cancer
      cells (LCC) into BALB/c nude mice. Intrpleural injection of recombinant human
      endostain (E), cisplatin (P) and recombinant human endostain combined with
      cisplatin (EP) was performed, MPE volume was measured, immunohistochemistry of
      CD31 was carried out to calculate micro vessel density (MVD), angiogenesis and
      apoptosis gene expression was detected. RESULTS: MPE volume was reduced by
      intrapleiral injection of recombinant human endostain and recombinant human
      endostain combined with cisplatin, MPE volume was positive correlated with MVD.
      Vescular epidermal growth factor-alpha (VEGF-alpha) expression reduced
      simultaneously with expression of hypoxia induced factor-1 (HIF1-alpha) elevated
      at the same time. CONCLUSIONS: MPE model could be made by intrapleural injection
      of LLC. Intrapleural injection of recombinant human endostain could reduce MPE
      volume of nude mice. The potential molecular mechanism of the therapeutical
      effects of intapleural injection of recombiant endostatin might be related to the
      downregulation of VEGF-alpha expression and neovascularization.?.

PMID- 25975297
TI  - [Effects of Local Radiation Combined with Chemotherapy in the treatment of
      ?Patients with Extensive-stage Small Cell Lung Cancer].
AB  - BACKGROUND AND OBJECTIVE: Chemotherapy is a highly efficient primary treatment
      for extensive-stage small cell lung cancer (ES-SCLC). However, patients receiving
      such treatment are prone to develop drug resistance. Local treatment is
      palliative and thus can alleviate the local symptoms and improve quality of life,
      but limited evidence is available for prolonging survival. Hence, this study
      evaluated the role of local treatment in chemotherapy of patients with ES-SCLC.
      METHODS: A total of 302 ES-SCLC cases were enrolled in this retrospective study.
      Prognostic factors were analyzed by Kaplan-Meier and Cox multivariate
      proportional hazards model. RESULTS: Median progression-free survival (PFS) and
      median survival time (MST) of the patients were 4.4 and 10.4 months,
      respectively. 1-, 2-, and 3-year survival rates were 37.8%, 10.2% and 4.4%,
      correspondingly. The MST of the primary tumor radiotherapy plus chemotherapy
      group was 14.3 months, whereas that of the chemotherapy group was 8.2 months
      (P<0.01). The MSTs of multiple-site, single-site, and non-metastasis local
      treatments were 18.7, 12.3 and 8.9 months, respectively (P<0.01). The MSTs of
      initiative, passive, and non-metastasis local treatments were 16.0, 10.9 and 9.4
      months, correspondingly (P<0.01). The MSTs of patients with prophylactic cranial
      irradiation (PCI) and those without PCI were 19.8 and 9.9 months, respectively
      (P<0.01). Primary tumor radiotherapy, metastasis local treatment, and PCI were
      independent prognostic factors for ES-SCLC. CONCLUSIONS: Primary tumor
      radiotherapy, metastasis local treatment, and PCI can significantly improve
      survival in patients with ES-SCLC.?.

PMID- 25975298
TI  - [Comparison of Efficacy and Safety of Different Therapeutic Regimens as ?Second
      line Treatment for Small Cell Lung Cancer].
AB  - BACKGROUND AND OBJECTIVE: Small-cell lung cancer (SCLC) is an aggressive disease
      for which the mainstay of treatment is cytotoxic chemotherapy. Despite good
      initial responses most patients will relapse or progress after the first-line
      therapy. The evidence of a benefit from second-line chemotherapy is limited in
      patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines,
      but more regimens are formulated based on experience in clinical. So we conducted
      this retrospective study in order to compare the efficacy and safety of different
      second-line treatment regimens. METHODS: We totally analyzed 309 patients
      received second-line treatment in our retrospective study. 157 patients received
      best supportive care (BSC), and the rest 152 patients received second-line
      chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used
      to analysis the differences among different groups. The endpoints were objective
      response rate (ORR), disease control rate (DCR), progression-free survival (PFS),
      and overall survival (OS). RESULTS: Patients administered second-line
      chemotherapy lived significantly longer, with a total OS from first-line therapy
      of 11.5 mo compared to 6.0 mo in patients with best supportive care alone
      (P<0.001), and the ORR, DCR, PFS and OS of the former (including the sensitive
      disease and resistance/refractory disease patients) were obviously better than
      that of the latter. The ORR and DCR of the patients who received second-line
      chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second
      line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line
      chemotherapy were divided by types of second-line regimens. The sensitive disease
      patients were from group A (VP-16-based rechallenge) and group B1 (CPT-11-based
      regimen). The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6%
      and 58.8%, respectively. There was no statistically significant difference
      (P=0.264; P=0.400). The median PFS from second-line chemotherapy of the two
      groups were 4.0 mo and 3.0 mo, and the second-line median OS were 6.5 mo and 4.5
      mo. There was no statistic difference (P=0.432; P=0.508). The
      resistance/refractory disease patients were divided into group B2 (CPT-11-based
      regimen), group C (PTX/DXL-based regimen) and group D (TPT-based regimen). There
      was no statistic difference in second-line ORR, DCR and median PFS among the
      three groups (P value is 0.521, 0.528 and 0.775, respectively); The median OS
      from second-line chemotherapy of the group D is longer than that of group B2 and
      group C, with statistical difference (P=0.043; P=0.030). The differences of grade
      III-IV hematologic toxicities among the four subgroups were not statistically
      different. The incidence of diarrhea in non-hematologic toxicities in patients
      who received irinotecan as second-line chemotherapy was higher than other three
      subgroups (P=0.029). CONCLUSIONS: Patients who progressed after the completion of
      first-line chemotherapy can gain survival benefit. The response and the PFS of
      the different second-line chemotherapies were similar. The patients who received
      the TPT-based regimen may gain longer overall survival than other
      resistance/refractory disease patients.?.

PMID- 25975299
TI  - [Three-dimensional Mass Measurement of Subsolid Pulmonary Nodules on Chest CT:
      Intra and Inter-observer Variability].
AB  - BACKGROUND: Subsolid pulmonary nodules tend to exhibit considerably slower growth
      rates than solid lesions, nevertheless, higher malignancy probability. The
      diagnosis of indeterminate nodules largely depends on the growth evaluation
      during follow-up. The growth can manifested as an increase in size or the
      appearance and/or subsequent increase of solid components. The mass reflect the
      product of volume and density and can be more sensitive in growth evaluation.
      However, the repeatability needs a further validation. The purpose of this study
      is to assess the intra and inter-observer variability of mass measurement for
      subsolid nodules. METHODS: 80 subsolid nodules in 44 patients were
      retrospectively enrolled. Both the volume and mass were measured by two
      radiologists using blind method independently. Intra-observer and inter-observer
      variability were analyzed and compared by Bland-Altman method intra-class
      correlation test and Wilcoxon test. RESULTS: Software achieved satisfied
      segmentation for 92.5% nodules. Of them, 35% underwent manual modification. The
      95% limits of agreement for intra-observer variability were -11.5%-10.4% for mass
      and -8.4%-8.8% for volume. The 95% limits of agreement for inter-observer
      variability were -17.4%-19.3% for mass and -17.9%-19.4% for volume.The intra
      class correlation foefficients between volume and mass measument was 0.95 and
      0.93 (both P<0.001) and no significant differences (P=0.78, 0.09) was found for
      intra- and inter-observer variability. Manual modification of the segmentation
      caused the worse mass measurement repeatability in spite of the reader
      satisfaction. CONCLUSIONS: The repeatability of mass measurement has no
      significant difference with that of volume measurement and may act as a reliable
      method in the follow-up of subsolid nodules.

PMID- 25975300
TI  - [Endobronchial Ultrasound-guided Transbronchial Needle Aspiration ?in the
      Diagnosis of Intrathoracic Metastasis from Extrapulmonary Malignancy].
AB  - BACKGROUND AND OBJECTIVE: Endobronchial ultrasound guided transbronchial needle
      aspiration (EBUS-TBNA) has been widely applied in diagnosing mediastinal and
      hilar adenopathy. This study is further to evaluate value and safety of EBUS-TBNA
      in diagnosing intrathoracic metastasis from extrapulmonary malignancy. METHODS:
      Prospectively analysis of 41 patients suspected intrathoracic metastasis from
      previous diagnosed/concurrent extrapulmonary malignancies in Shanghai Chest
      Hospital, with radiologic findings showing mediastinal/hilar lymph node
      enlargement or intrapulmonary lesion requiring EBUS-TBNA examination for
      pathological diagnosis. RESULTS: 41 candidate patients enrolled, and 67
      mediastinal/hilar lymph nodes and 5 intrapulmonary lesions were aspirated. 14
      intrathoracic metastasis, 10 primary lung cancer, 9 reactive lymphadenitis, 4
      sarcoid-like reactions, and 1 tuberculosis was diagnosed by EBUS-TBNA.
      Sensitivity and accuracy of EBUS-TBNA in diagnosing intrathoracic metastasis was
      87.50% and 95.12%, respectively. Immunohistochemistry (IHC) was performed in 18
      malignant tumors to obtain definite type or origin, twelve intrathoracic
      metastasis and 6 primary lung cancer were further confirmed. CONCLUSIONS: EBUS
      TBNA is a safe, effective method for the diagnosis of intrathoracic metastasis
      from extrapulmonary malignancy. IHC can provide additional evidence for
      distinguishing extrapulmonary malignancy from primary lung cancer.

PMID- 25975301
TI  - [Stereotactic Radiotherapy for Non-small Cell Lung Cancer with Small Lesions?
      Applying A Flattening Filter Free Clinac].
AB  - BACKGROUND AND OBJECTIVE: With the rapid development of technology, stereotactic
      radiotherapy has been widely used. In a cohort of medically operable non-small
      cell lung cancer patients receiving stereotactic body radiation therapy (SBRT)
      survival rates "potentially equivalent to those of surgery" have been reported.
      Removing the field flattening filter, Clinac is capable of delivering dose rates
      much higher than conventional linac as well as reducing the treatment time. The
      goals of this work were to report safety and efficacy of SBRT treatment using a
      flattening filter-free model for non-small cell lung cancer (NSCLC) with small
      lesions. METHODS: From December 2011 to December 2013, 31 NSCLC patients who were
      T1-2N0M0, solitary pulmonary recurrence after surgery, and stage IV with oligo
      metastasis were enrolled, receiving SBRT treatment (60 Gy/8 f or 48 Gy/4 f)
      applying a flattening filter-free model. RESULTS: Compared with conventional
      technique, flattening filter-free model shortened the treating time with
      equivalent target dose and normal tissue dose. The median follow-up time is 19.4
      mo. The 1-yr local control, regional control, distant control, progression free
      survival and overall survival rates were 96.8%, 96.8%, 83.9%, 77.4% and 96.8%.
      The most common side effects were radiation pneumonitis (29% grade 1, 3.2% grade
      2) and chest pain (12.9% grade 1, 6.5% grade 2). CONCLUSIONS: The use of
      flattening filter-free model in SBRT for small lesions of NSCLC patients is safe
      and effective. Long time follow-up and additional studies are still needed to
      validate our conclusions.

PMID- 25975302
TI  - [Sequential Treatment of Advanced Squamous Lung Cancer: ?First-line Gemcitabine
      +/- platinum Followed by Second-line Taxanes +/- platinum Versus Reverse
      Sequence].
AB  - BACKGROUND AND OBJECTIVE: Gemcitabine and taxanes are effective agents commonly
      used in advanced squamous lung cancer. The best treatment sequence, however, is
      unclear to our knowledge. So we conducted this retrospective study in order to
      compare the efficacy and toxicities of first-line Gemcitabine +/- platinum
      followed by second-line taxanes +/- platinum with the reverse sequence. METHODS:
      We totally analyzed 105 patients with stage IIIb-IV squamous lung cancer in our
      retrospective study. There were 49 patients receiving gemcitabine +/- platinum
      first-line followed by taxanes +/- platinum second-line (G-T group), and 56
      patients receiving taxanes +/- platinum first-line followed by gemcitabine +/-
      platinum second-line (T-G group). The primary endpoint of the study was overall
      survival (OS), and the secondary endpoints included progression-free survival
      (PFS), objective response rate (ORR), disease control rate (DCR) and toxicities.
      RESULTS: The median OS were 18.5 mo in G-T group and 19.0 mo in T-G group
      (P=0.520). The median PFS1 was 5.0 mo and 4.0 mo with first-line gemcitabine +/-
      platinum and taxanes +/- platinum, respectively (P=0.584). The median PFS2 was
      2.7 mo and 2.5 mo with second-line gemcitabine +/- platinum and taxanes +/-
      platinum (P=0.432). The ORR1 of G-T group and T-G group were 36.73% and 33.92%
      (P=0.577), and DCR1 were 79.59% and 89.29% (P=0.186); the ORR2 of G-T group and T
      G group were 4.08% and 5.36% (P=0.085), and DCR2 were 51.02% and 66.07%,
      respectively (P=0.118). Hematologic toxicities was more frequent in G-T group,
      the patients experienced more grade 3-4 lower hemoglobin (P=0.027) and
      thrombocytopenia (P=0.002). CONCLUSIONS: The efficacy of first line gemcitabine
      +/- platinum followed by second line taxanes +/- platinum and the reverse
      sequence was similar, and the toxicities was tolerable. Both sequential patterns
      were effective in advanced squamous lung cancer.?.

PMID- 25975304
TI  - Safe endovascular retrieval of a vena cava filter after duodenal and pancreatic
      perforation and associated recurrent pancreatitis.

PMID- 25975303
TI  - [Advances in Association of Estrogen and Human Non-small Cell Lung Cancer].
AB  - Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC),
      is the most leading cause of cancer mortality throughout the world. Despite
      recent improvements in its treatment, it still remains a highly lethal disease.
      It is becoming increasingly clear that estrogen and estrogen receptors are
      involve in the pathogenesis and development of lung cancer. Estrogen receptor
      modulators and aromatase inhibitor may reverse the drug-resistance of platinum
      based chemotherapy in NSCLC patients and can enhance curative effect of epidermal
      growth factor receptor tyrosine kinase inhibitor. In this article the progress in
      the function of estrogen in NSCLC and the treatment based on the ER signaling
      pathways for NSCLC is reviewed. 

PMID- 25975305
TI  - ACGME-recognized international surgery rotation: a step in the right direction?
      or testing unknown waters.

PMID- 25975306
TI  - Bilateral synchronous benign phyllodes tumors.

PMID- 25975307
TI  - Laparoscopic choledochoduodenostomy: an option in cases of obstructive biliary
      tract.

PMID- 25975309
TI  - Gallbladder torsion in a 91-year-old female: an unusual cause of right upper
      quadrant pain.

PMID- 25975308
TI  - The incidence of gastrointestinal stromal tumors is increased in obese
      individuals.

PMID- 25975310
TI  - Post-traumatic carotid artery dissection in children.

PMID- 25975311
TI  - Clinical cases of nonsurgical pneumoperitoneum: categorizing the disease and
      treatment options.

PMID- 25975312
TI  - Total single-stage breast reconstruction with free nipple grafts using the
      salvage of parts concept.

PMID- 25975313
TI  - Melanoma metastases to gastrointestinal tract.

PMID- 25975314
TI  - Giant condyloma acuminatum of the scrotum, bilateral groins, and suprapubic
      region: a treatment and reconstruction challenge.

PMID- 25975315
TI  - Aortic dissection after cardiopulmonary resuscitation.

PMID- 25975316
TI  - Laparoscopic cholecystectomy performed by acute care surgeons and general
      surgeons.

PMID- 25975317
TI  - Electrochemotherapy treatment of cutaneous metastases from breast cancer.

PMID- 25975318
TI  - A novel use of N-acetylcystine for the management of recurrent small bowel pseudo
      obstruction in a patient with autoimmune autonomic ganglionopathy.

PMID- 25975319
TI  - Elevated fluid CEA levels in a pancreatic lymphoepithelial cyst.

PMID- 25975320
TI  - International surgical rotation: a prodigious personal and professional
      maturation.

PMID- 25975321
TI  - Sigmoid perforation due to toothpick ingestion leading to hydronephrosis and
      urosepsis.

PMID- 25975322
TI  - Large pseudocyst of the spleen: etiology, diagnosis, and treatment for general
      surgeons.

PMID- 25975323
TI  - Frederic E. Mohs, M.D. (1910-2002): physician and innovator.

PMID- 25975324
TI  - Timing of optimal surgical intervention for neonates with necrotizing
      enterocolitis.
AB  - Up to half of all patients with necrotizing enterocolitis require acute surgical
      treatment. Determining when to operate on these patients can be challenging.
      Utilizing a combination of clinical and metabolic indicators, we sought to
      identify the optimal timing of surgical intervention. A retrospective chart
      review was conducted on patients with necrotizing enterocolitis from 2001 to
      2010. Previously validated clinical (abdominal erythema, palpable abdominal mass,
      hypotension), radiographic (pneumoperitoneum, portal venous gas, fixed bowel
      loop, severe pneumatosis intestinalis), and laboratory (acidosis, bacteremia,
      hyponatremia, bandemia, neutropenia, thrombocytopenia) indicators were assessed
      for the ability to predict the need for acute surgical intervention as a simple
      indicator score, based on the sum of the indicators listed above. A total of 197
      patients were included. One hundred and twenty-four procedures (28 peritoneal
      drains, 96 laparotomy) were performed on 122 patients (62%). Median indicator
      score was 4 (range: 0-8). Logistic regression identified abdominal erythema (odds
      ratio [OR] = 3.3, P = 0.001), acidosis (OR = 2.6, P = 0.004), and hypotension (OR
      = 1.9, P = 0.05) as independently associated with surgical intervention. A
      significant increase in surgical intervention was noted for patients with
      indicator score of 3 or more. In conclusion, if three or more indicators exist,
      operative intervention is very likely required. In the absence of
      pneumoperitoneum, abdominal erythema, acidosis, and hypotension are especially
      important. 

PMID- 25975325
TI  - The impact of surgical diversion before neoadjuvant therapy for rectal cancer.
AB  - Up-front fecal diversion can palliate emergent symptoms related to locally
      advanced rectal cancer (LARC) allowing patients to receive neoadjuvant
      chemoradiation therapy (nCRT). We analyzed outcomes of pretreatment-diverted LARC
      patients relative to nondiverted patients to define the impact of this management
      strategy. We retrospectively collected data on 103 LARC patients treated with
      nCRT and surgery. Medical records were reviewed for patient characteristics,
      staging, treatment plan, and outcomes. Thirteen LARC patients underwent
      pretreatment diversion for urgent symptoms and 90 LARC patients proceeded
      directly to nCRT. In all, 50 per cent of diverted patients presented with T4
      tumor compared with 14 per cent in the nondiverted patients (P = 0.003). Diverted
      patients experienced a delay in time-to-treatment initiation of 12 days, although
      this difference was not statistically significant. Similar rates of
      chemoradiation and surgical toxicities were observed. Even though diverted
      patients demonstrated less pathologic response to nCRT compared with nondiverted
      patients (P = 0.04), there was no significant difference in overall survival. In
      conclusion, our study demonstrates the effectiveness of up-front fecal diversion
      at managing emergent obstructive symptoms related to advanced rectal cancer
      without additional complications, allowing patients to proceed with nCRT followed
      by radical surgery. 

PMID- 25975326
TI  - Treatment of esophagojejunal anastomosis leakage: a systematic review from the
      last two decades.
AB  - Esophagojejunal anastomosis leakage is one of the major complications after total
      gastrectomy for gastric cancer and is an independent predictor of survival. Our
      aim is to systematically review the literature and discuss the reported
      therapeutic approaches to identify the best therapeutic approach. Pubmed, EMbase,
      Cochrane Library, CILEA Archive, BMJ Clinical Evidence, and Up ToDate databases
      were screened limiting the research to articles written in English from January
      1992 through December 2013. This way a total of 474 manuscripts were retrieved
      for furthermore evaluation. Eleven manuscripts were considered eligible and the
      study is focused on those works. We analyzed a total of 3,893 patients and 114
      cases of esophagojejunal anastomosis leakage. Different treatments were grouped
      into three main categories: conservative approach (66 cases), endoscopic approach
      (21 cases), and surgical approach (27 cases). The overall mortality rate is 26.32
      per cent and surgical approach showed the higher rate. According to the reported
      data, a complete resolution of the leakage can be achieved in an interval ranging
      from 7 to 28 days in the group treated conservatively. Conservative approach
      should always be considered as the treatment of choice. Reoperation may be
      necessary in case of wide dehiscence or when other treatments fail; therefore,
      the high mortality rate related to this procedure is due to the comorbidities of
      patients undergoing relaparotomy. Finally, endoscopic approach with endoclips
      seems promising but needs furthermore studies. 

PMID- 25975327
TI  - Evaluating one day versus two days preoperative lymphoscintigraphy protocols for
      sentinel lymph node biopsy in breast cancer.
AB  - Sentinel lymph node biopsy (SLNB) is used to detect axillary lymph node
      metastases in breast cancer. Preoperative radiocolloid injection with
      lymphoscintigraphy (PL) is performed before SLNB. Few comparisons between 1- and
      2-day PL protocols exist. Opponents of a 2-day protocol have expressed concerns
      of radiotracer washout to nonsentinel nodes. Proponents cite lack of scheduling
      conflicts between PL and surgery. A total of 387 consecutive patients with
      clinically node-negative breast cancer underwent SLNB with PL. Lymphoscintigraphy
      images were obtained within 30 minutes of radiocolloid injection. Axillary lymph
      node dissection was performed if the sentinel lymph node (SLN) could not be
      identified. Data were collected regarding PL technique and results. In all, 212
      patients were included in the 2-day PL group and 175 patients in the 1-day PL
      group. Lymphoscintigraphy identified an axillary sentinel node in 143/212 (67.5%)
      of patients in the 2-day group and 127/175 (72.5%) in the 1-day group (P = 0.28).
      SLN was identified at surgery in 209/212 (98.6%) patients in the 2-day group and
      174/175 (99.4%) in the 1-day group (P = 0.41). An average of 3 SLN was found at
      surgery in the 2-day group compared with 3.15 in the 1-day group (P = 0.43). SLN
      was positive for metastatic disease in 54/212 (25.5%) patients in the 2-day group
      compared with 40/175 (22.9%) in the 1-day group (P = 0.55). A 2-day
      lymphoscintigraphy protocol allows reliable detection of the SLN, of positive SLN
      and equivalent SLN harvest compared with a 1-day protocol. The timing of
      radiocolloid injection before SLNB can be left at the discretion of the surgeon. 

PMID- 25975328
TI  - Immediate versus delayed repair of destructive bowel injuries in patients with an
      open abdomen.
AB  - Trauma surgeons frequently encounter destructive bowel injuries. The timing of
      the repair of the bowel injury should be performed in patients with planned open
      abdomen management and second-look laparotomy has not been specifically
      addressed. Our primary objective was to determine if there was a significant
      difference in the incidence of major complications between immediate and delayed
      repair among patients with traumatic bowel injuries and planned open abdomens.
      This was a retrospective cohort study of adult patients with traumatic bowel
      injuries treated between 2001 and 2011 and who underwent laparotomy and were left
      with an open abdomen with a planned second operation. Pediatric patients (age
      less than 15 years) and patients who died in the first 24 hours of admission were
      excluded. The primary exposure of interest was dichotomously defined based on
      either definitive repair of the bowel injury during the initial trauma operation
      (immediate) or definitive repair during a subsequent surgery (delayed). Major
      complications were defined as enterocutaneous fistula, dehiscence, and abscess.
      Ninety-two patients met study eligibility. Of these, 50 (54%) underwent immediate
      bowel repair. Univariate analysis suggested no significant differences in the
      proportion of major complications between the two groups. After adjusting for
      Injury Severity Score, penetrating injury, initial base deficit, and presence of
      colon injury, there was no statistical difference in incidence of major
      complications between the two groups. Patients undergoing immediate Versus
      delayed repair of traumatic bowel injuries and who are left with an open abdomen
      have comparable outcomes in terms of major complications. 

PMID- 25975329
TI  - Differential outcome of fissure-positioned tube in closed thoracostomy for
      primary spontaneous pneumothorax.
AB  - Closed tube thoracostomy is often used to evacuate a primary spontaneous
      pneumothorax (PSP). Occasionally, this procedure is complicated by placement of
      the chest tube location in the fissural area instead of pleural space. There is a
      paucity of studies on outcomes according to chest tube placement. As such, we
      investigated outcomes of chest tube placement in fissural versus pleural area in
      closed thoracostomy for PSP. Patients between 14 and 65 years of age who had been
      treated with chest tube insertion to evacuate PSP were selected based on
      retrospective review of medical records. Patients selected for this study
      received chest tube placement at either the fissural or pleural spaces. Those
      with pre-existing lung disease or those transferred into our hospital after
      closed thoracostomy were excluded. Of the 255 patients with PSP treated with
      chest tube insertion, 172 patients were enrolled in this study. Twenty-nine
      (16.9%) had fissural tube placement and 143 (83.1%) had pleural tube placement. A
      higher proportion of patients in the fissural versus pleural group required
      additional chest tube insertion (20.7% vs 4.9%, P = 0.010, respectively). There
      was no significant difference in body mass index, smoker status, symptom
      duration, number of episodes, post-thoracostomy complications, need for
      subsequent management, and duration of hospitalization in either group. In closed
      thoracostomy for PSP, there is a higher chance of tube dysfunction when the chest
      tube is positioned at fissural area as compared with the pleural space. 

PMID- 25975330
TI  - Gastric electrical stimulation for refractory gastroparesis: predictors of
      response and redefining a successful outcome.
AB  - Predictors of a favorable response and measures of success with gastric
      electrical stimulation (GES) for gastroparesis remain elusive. Published results
      remain inconsistent with respect to patient perceived benefit, despite
      statistical improvements in objective measures of symptom severity. We performed
      a retrospective analysis of 56 patients with gastroparesis who underwent
      insertion of a gastric electrical stimulator during the study period. Data
      included demographics, symptoms, total symptom severity score (TSS, range 0-24,
      initial and most recent), and gastric emptying times. TSS were grouped into four
      severity categories (0-10, 11-14, 15-18, 19-24). TSS improvement was defined as
      movement to a lower severity category. Perception of improvement was compared
      with that of TSS score improvement using chi(2) test. Etiology as a predictor of
      improvement was measured using logistic regression. Initial mean TSS was 21, and
      post-treatment TSS was 13.5. Improvement was significant for individual symptoms
      and in reduction of TSS for both diabetic/idiopathic etiologies (P <= 0.001). No
      correlation was noted between likelihood of success/failure and gastric emptying
      times (P = 0.32). Thirty-eight improved (moved to lower TSS category), whereas 18
      failed (remained in same category) (P <= 0.001), which correlated with perception
      of improvement. Of 18 failures, 14 (77.7%) were idiopathic. On logistic
      regression, diabetics were more likely than idiopathic patients to move to a
      lower TSS category (odds ratio 14, P = 0.003) and even more likely to improve
      based on patient perception (odds ratio 45, P = 0.005). GES produces far more
      consistent improvement in diabetics. Further study of GES in idiopathic
      gastroparesis is needed. Application of the proposed TSS severity categories
      allowed differentiation of small, statistically significant (but clinically
      insignificant) reductions in TSS from larger, clinically significant reductions,
      thereby permitting more reliable application of TSS to the evaluation of GES
      efficacy. 

PMID- 25975331
TI  - Outpatient parathyroid surgery: ten-year experience: is it safe?
AB  - Outpatient parathyroid surgery is increasing in frequency especially for patients
      undergoing minimally invasive operations. From January 1, 2000 to December 31,
      2009, 585 operations were performed on patients with untreated primary
      hyperparathyroidism. Outpatient operations were performed on 43 per cent
      (249/585), whereas 57 per cent (336/585) were admitted. Comorbidities were
      present in 63 per cent of outpatients and 72 per cent of inpatients, whereas
      systemic complications occurred in 0.8 per cent of outpatients and 7 per cent of
      inpatients. Ninety-four per cent of outpatients were minimally invasive although
      inpatient procedures were evenly divided. Local complications were low (8% and
      6%) in both groups. Using zip codes to determine distance from home to hospital,
      no differences were noted. Readmission rates were low (<0.5%) and the same in
      each group. Inpatients longer than 23 hours tended to be older with higher local
      and systemic complication rates. Over a decade, most patients undergoing same day
      parathyroid surgery had minimally invasive operations with lower comorbidities
      and lower systemic complications than inpatients. Minimally invasive and less
      complex nonminimally invasive operations can safely be performed on an outpatient
      basis with careful patient selection. Patient with more severe comorbidities and
      multiple comorbidities are less favorable candidates for outpatient surgery
      because of a higher risk of systemic complications. 

PMID- 25975332
TI  - Delayed manifestations of laparoscopic bowel injury.
AB  - Bowel injury (BI) is a complication of open and laparoscopic abdominal surgery
      associated with increased morbidity and mortality. If BI is missed at the time it
      occurs, it can have devastating consequences. Electrosurgery is used extensively
      in laparoscopic surgery and can cause thermal injuries that are harder to detect
      than mechanical injuries and may evolve over time. The medical literature of the
      past 10 years was searched for large series and compilation studies reporting
      overall incidence of and mortality from BI in laparoscopy, and the results of
      seven relevant articles, which included over 300,000 procedures, were analyzed
      and tabulated. The literature was then reviewed for additional information about
      the specific incidence and outcome of missed BI and the role of electrosurgical
      thermal sources in causing BI. BI is underreported, frequently missed at surgery,
      and results in significant morbidity and mortality that can be ground for
      malpractice claims against the surgeon. Thermal injury from electrosurgical
      instruments may be involved in a number of injuries in laparoscopic surgery.
      Nearly undetectable partial-thickness thermal injury may play a role in the
      atypical and delayed presentation of some cases of BI. 

PMID- 25975333
TI  - Radiofrequency ablation of the pancreas: protective effect of local cooling
      techniques.
AB  - Pancreatic carcinoma is one of the commonest malignant diseases today and the
      majority of patients are suitable for palliative treatment only. Radiofrequency
      ablation (RFA) has been used extensively for the treatment of solid organ tumors
      but little is known on the efficacy and safety of pancreatic ablation. To further
      investigate the safety of pancreatic RFA, 18 pigs had RFA of the pancreas, close
      to superior mesenteric vein and duodenum. Group A (nine animals) was protected
      with peripancreatic cool perfusion and Group B (nine animals) with portal vein
      (PV) intravenous injection of cool saline. Biochemical and histological evidence
      suggested lateral thermal injury of the duodenal wall and superior mesenteric
      vein and acute pancreatitis in most animals. However, clinically and at autopsy,
      Group B animals fared much better. PV thrombosis, hepatic abscess, duodenal
      perforation, ascites, and extensive pancreatic necrosis were observed in Group A
      but not in Group B. The present study suggests that PV cool saline perfusion can
      prevent major complications caused by pancreatic RFA and may be used in
      combination with other protective techniques in the clinical setting to reduce
      RFA-associated morbidity. 

PMID- 25975334
TI  - Risk factors for the development of an incisional hernia after sigmoid resection
      for diverticulitis: an analysis of 33 patients, operative and disease-associated
      factors.
AB  - Incisional hernia (IH) is a relatively common sequelae of sigmoidectomy for
      diverticulitis. The aim of this study was to investigate factors that may predict
      IH in diverticulitis patients. Two hundred and one diverticulitis patients
      undergoing sigmoidectomy between January 2002 and December 2012 were identified
      (mean follow-up 5.15 +/- 2.33 years). Patients with wound infections were
      excluded. Thirteen patient-associated, three diverticular disease-related, and 17
      operative variables were evaluated in patients with and without IH. Volumetric
      fat was measured on preoperative CTs. Fischer's exact, chi(2), and Mann-Whitney
      tests and multivariate regression analysis were used for statistics. Thirty-four
      (17%) patients had an IH. On multivariate analysis, wound packing (OR 3.4, P =
      0.017), postoperative nonwound infection (OR 7.4, P = 0.014), and previous hernia
      (OR 3.6, P = 0.005) were as independent predictors of IH. Fifteen of 34 (44%)
      patients who developed a hernia had a history of prior hernia. Of 33 potential
      risk factors analyzed, including smoking, chronic obstructive pulmonary disease,
      and obesity, the only patient factor present preoperatively associated with
      increased risk of a postsigmoidectomy hernia after multivariate analysis was a
      history of a previous hernia. Preoperative identification of patients with a
      history of hernia offers the opportunity to employ measures to decrease the
      likelihood of IH. 

PMID- 25975335
TI  - Short-term results of treating primary and recurrent anal fistulas with a novel
      extracellular matrix derived from porcine urinary bladder.
AB  - Anal fistulas are difficult to treat because they are often recalcitrant to
      medical therapies and surgical treatment may lead to significant morbidities. A
      recent novel biologically derived graft from porcine urinary bladder
      (MatriStem(TM)) has shown great promise in experimental studies of tissue
      regeneration in diverse tissues. The objectives of this study were to evaluate
      the safety and short-term efficacy of MatriStem for treatment of anal fistulas.
      This was a retrospective study of patients treated from January 3, 2012 to March
      3, 2014 at the University of Pittsburgh Medical Center. MatriStem was used to
      treat patients with anal fistulas by implanting it uniformly with a single
      application in all patients using a standardized protocol. Data were collected
      retrospectively from hospital records and office charts. Nineteen fistulas were
      treated with MatriStem. There were no adverse complications. Overall efficacy of
      MatriStem was 79 per cent with healing occurring in a mean time of 17 days and
      mean follow-up of seven months (range 1-26 months). MatriStem was effective in
      healing in 75 per cent of primary anal fistulas and 86 per cent of recurrent
      fistulas. MatriStem seems to be a safe and promising treatment for primary and
      recurrent anal fistulas, and warrants further study and clinical trials to
      substantiate widespread clinical use. 

PMID- 25975336
TI  - The utility of the matrix format for surgical morbidity and mortality conference.
AB  - With the limitations posed by increasing work hour restrictions, surgical
      residency programs are focusing more on maximizing the educational benefit of
      their conferences. The Morbidity and Mortality (M&M) conference serves as a forum
      to discuss adverse events and patient care improvement using evidence-based
      medicine. The matrix format (MF) is an enhancement to the traditional format
      (TF), focusing on the case selection process and a postconference newsletter
      reiterating the relevant literature review and discussion points. Our institution
      adopted the MF to evaluate both its short- and long-term educational values.
      Surveys were distributed to residents and faculty within the Department of
      General Surgery to assess their interest and satisfaction, perception of
      educational value, and efficiency with the MF compared with the TF. Responses
      were obtained from 22/22 (100%) residents for the TF and 11/23 (48%) for the MF.
      Faculty responses were 19/19 (100%) and 9/16 (56%), respectively. Reasons for an
      overall decreased response with the MF were not investigated further, as
      participation was strictly voluntary. Our results confirmed an overall approval
      of the MF by both residents and faculty. Faculty reported an improved efficiency
      of the conference (P < 0.039), encompassing improved content and presentation
      quality. Residents reported an improved overall interest and satisfaction with
      the MF (P < 0.001) as well as an improvement in the educational value (P <
      0.007). Residents spent less time preparing presentations and reported learning
      greater educational benefit to the conference when preparing their own
      presentations (P < 0.001). In conclusion, the MF resulted in a greater overall
      satisfaction for residents and attending surgeons with an increased investment by
      the audience and overall improvement in perceived educational benefit. 

PMID- 25975337
TI  - Elective laparoscopic adrenalectomy outcomes in 1099 ACS NSQIP patients:
      identifying candidates for early discharge.
AB  - This study evaluates the risk of complications associated with elective
      laparoscopic adrenalectomy (LA) as reported in a national dataset. We hypothesize
      that the risk for major complication is associated with identifiable
      perioperative variables. This information may aid in understanding who safely
      could be discharged early after surgery, including same-day discharge. Elective
      LA from 2009 to 2010 American College of Surgeons National Surgical Quality
      Improvement Program Participant Use File were reviewed. A priori selection of
      likely risk factors for complications was assessed for their association with
      morbidity. Sequential bivariable logistic regression was used to measure the
      statistical significance of each risk factor's observed association with the
      occurrence of major morbidity after surgery. The potential for multiple
      comparisons bias was accounted for by using a high threshold (P < 0.01) for
      identifying statistically significant associations. One thousand ninety-nine
      patients were identified. The 30-day mortality rate was 0.18 per cent, and 4.8
      per cent of patients experienced a major morbidity within 30 days of surgery.
      Return to the operating room occurred in 1.46 per cent of cases. Statistically
      significant associations occurred for 15 patient characteristics at P < 0.05.
      Diabetes, nonindependent functional status before surgery, American Society of
      Anesthesiologists classification >2, and operative time were statistically
      significant at P < 0.01. Complications are rare events among elective LA
      patients. However, several readily identifiable patient characteristics are
      associated with the occurrence of complications among these patients. These
      patient characteristics should be taken into account when considering future
      trials of early discharge after LA, including same-day discharge. 

PMID- 25975338
TI  - Objective comparison of animal training versus artificial simulation for initial
      cricothyroidotomy training.
AB  - This manuscript aims to determine if there is a difference in performance
      outcomes after initial training with either animals or simulators. Volunteers
      without prior experience performing emergency procedures were randomly assigned
      to receive training in cricothyroidotomy on either a pig model or on an
      artificial simulator. Volunteers were given identical lectures and trained to
      proficiency. Two weeks after training, trainees were tested using human cadavers
      as to their performance with time, incision size, incision start location,
      initial placement attempt, and final accuracy. Overall success rate of the animal
      trained group was 64 per cent and in the artificial simulator group, 73 per cent
      (P = 0.431). Median time to completion in the animal group and artificial
      simulator group was 143 s and 105 s (P = 0.482), and incision lengths 4.0 cm and
      3.2 cm (P = 0.173), respectively. Accuracy of initially attempted incision
      placement and final cricothyroidotomy tube placement was also compared. Initially
      attempted site accuracy in the animal-trained group was 93 per cent and correct
      final position 79 per cent, and in the artificial group, 100 per cent (P = 0.452)
      and 88 per cent (P = 0.782), respectively. There was no statistically
      significant, objective difference in any metric between animal- and simulator
      trained groups after cricothyroidotomy training. For initial training, there is
      no objective benefit of animal training. 

PMID- 25975339
TI  - Financial implication of proposed legislation on hospital reimbursement for the
      injured drunk driver.
AB  - The state of Michigan currently has no-fault automobile insurance with personal
      injury protection, providing anyone injured in motor vehicle collisions with
      unlimited medical and rehabilitation benefits and lost wage recovery. A new bill
      proposal, Michigan House Bill 5588, will eliminate hospital reimbursement for
      those who are found to be intoxicated at the time of a motor vehicle collision.
      These medical costs will be passed on to patients, which may result in a large
      reimbursement deficit for hospitals caring for these patients. This retrospective
      review examines the costs of caring for all intoxicated drivers who were admitted
      to a Level 1 trauma center after a motor vehicle collision over a 2-year period.
      Intoxicated drivers were younger (P = 0.0002), had a lower Glasgow Coma Scale (P
      = 0.0013), and were more likely to meet Level 1 trauma criteria (P = 0.0002). The
      sum of total charges for injured drunk drivers totaled $5.2 million. When taking
      into account fixed and variable costs of care, lost hospital net income would be
      $3 million (21.9%) over a 3-year span whether House Bill 5588 passes. In
      conclusion, the passage of House Bill 5588 will lead to a large financial burden
      for hospitals that treat intoxicated drivers. 

PMID- 25975340
TI  - Impact of vascular invasion of a primary tumor as a strong risk factor for
      disease recurrence in patients with node-positive breast cancer.
AB  - The presence of lymph node metastasis is considered to be the most significant
      indicator of prognosis. However, in some cases with node-positive breast cancer,
      cancer cell dissemination is localized to the lymphatic systems. It is,
      therefore, important to develop selection criteria for strong adjuvant therapy in
      patients with node-positive breast cancer. This study was undertaken to evaluate
      the presence of vascular invasion that may reflect systemic disease as a
      predictor of disease recurrence in node-positive breast cancer. We
      retrospectively evaluated the cases of 134 consecutive female patients with
      breast cancer with lymph node metastasis who underwent radical breast operations.
      We examined the relationship between recurrence and clinicopathological factors,
      particularly vascular invasion. The presence of vascular invasion was found to be
      significant in a univariate analysis. The presence of vascular invasion was the
      independent risk factor in a multivariate analysis. Among the 66 patients without
      vascular invasion, four (6.1%) had disease recurrence. On the other hand, among
      the 68 patients with vascular invasion, 15 (22.1%) had a recurrence. It is
      interesting to note that despite the presence of lymph node metastasis, the group
      without vascular invasion had few patients with distant metastases. Our results
      suggest that the presence of vascular invasion could be an indicator of high
      biological aggressiveness and may be a strong prognostic factor for node-positive
      breast cancer. 

PMID- 25975341
TI  - Emergency central venous catheterization during trauma resuscitation: a safety
      analysis by site.
AB  - Central venous catheterization (CVC) is often necessary during initial trauma
      resuscitations, but may cause complications including catheter-related blood
      stream infection (CRBSI), deep venous thrombosis (DVT), pulmonary emboli (PE),
      arterial injury, or pneumothoraces. Our primary objective compared subclavian
      versus femoral CVC complications during initial trauma resuscitations. A
      retrospective review (2010-2011) at an urban, Level-I Trauma Center reviewed CVCs
      during initial trauma resuscitations. Demographics, clinical characteristics, and
      complications including: CRBSIs, DVTs, arterial injuries, pneumothoraces, and PEs
      were analyzed. Fisher's exact test and Student's t test were used; P <= 0.05 was
      considered statistically significant. Overall, 504 CVCs were placed (subclavian,
      n = 259; femoral, n = 245). No difference in age (47 +/- 22 vs 45 +/- 23 years)
      or body mass index (28 +/- 6 vs 29 +/- 16 kg/m(2)) was detected (P > 0.05) in
      subclavian vs femoral CVC, but subclavian CVCs had more blunt injuries (81% vs
      69%), greater systolic blood pressure (95 +/- 55 vs 83 +/- 43 mmHg), greater
      Glasgow Coma Scale (10 +/- 5 vs 9 +/- 5), and less introducers (49% vs 73%) than
      femoral CVCs (all P < 0.05). Catheter related arterial injuries, PEs, and CRBSIs
      were similar in subclavian and femoral groups (3% vs 2%, 0% vs 1%, and 3% vs 3%;
      all P > 0.05). Catheter-related DVTs occurred in 2 per cent of subclavian and 9
      per cent of femoral CVCs (P < 0.001). There was a 3 per cent occurrence of
      pneumothorax in the subclavian CVC population. In conclusion, both subclavian and
      femoral CVCs caused significant complications. Subclavian catheter-related
      pneumothoraces occurred more commonly and femoral CRBSIs less commonly than
      expected compared with prior literature in nonemergent scenarios. This suggests
      that femoral CVC may be safer than subclavian CVC during initial trauma
      resuscitations. 

PMID- 25975342
TI  - Is interval appendectomy indicated after non-operative management of acute
      appendicitis in patients with cancer? A retrospective review from a single
      institution.
AB  - Interval appendectomy (IA) is a controversial subject, with little consensus on
      its use in patients undergoing treatment for malignancy. We sought to determine
      the frequency of recurrent appendicitis in cancer patients managed nonoperatively
      (NOM) during index hospitalization (IHA) for acute appendicitis (AA). Clinical
      presentation, cancer treatment, and follow-up were collected from electronic
      medical records of patients with CT scan-confirmed AA treated at a single
      institution between August 1999 and August 2009. Seventy-two of 109 AA patients
      underwent appendectomy during IHA; 34 of these 109 were NOM during IHA. Median
      index length of NOM patients' stay was six days (0-55), median age was 59 (18-80)
      years. Indications for NOM were presence of abscess or phlegmon (14), mild
      symptoms (13), high surgical risk (3), end-stage cancer (3), and patient
      declining surgery (1). Eight NOM patients underwent percutaneous drainage of
      abdominal abscess (median total duration of intravenous + oral antibiotics = 12
      days [0-55]). There were six deaths (1 IHA, 5 NOM): four sepsis and two cancer
      progression. At a median of 19-month follow-up (range 1-103), four NOM patients
      surviving IHA had recurrent AA (11.7%) at two (n = 2) and three months (n = 2)
      after the first episode. Overall, six had IA (17.6%) one to seven months post AA;
      25 remained asymptomatic, without IA. In conclusion, among NOM patients at a
      cancer center at IHA for AA, recurrent AA was early (<4 months) but uncommon. IA
      should be offered to those with recurrent symptoms, but appears to have a very
      limited role after several months of asymptomatic follow-up. 

PMID- 25975343
TI  - Measuring satisfaction: factors that drive hospital consumer assessment of
      healthcare providers and systems survey responses in a trauma and acute care
      surgery population.
AB  - Hospital quality metrics now reflect patient satisfaction and are measured by
      Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)
      surveys. Understanding these metrics and drivers will be integral in providing
      quality care as this process evolves. This study identifies factors associated
      with patient satisfaction as determined by HCAHPS survey responses in trauma and
      acute care surgery patients. HCAHPS survey responses from acute care surgery and
      trauma patients at a single institution between 3/11 and 10/12 were analyzed.
      Logistic regression determined which responses to individual HCAHPS questions
      predicted highest hospital score (a rating of 9-10/10). Demographic and clinical
      variables were also analyzed as predictors of satisfaction. Subgroup analysis for
      trauma patients was performed. In 70.3 per cent of 182 total survey responses, a
      9-10/10 score was given. The strongest predictors of highest hospital ranking
      were respect from doctors (odds ratio [OR] = 24.5, confidence interval [CI]: 5.44
      110.4), doctors listening (OR: 9.33, CI: 3.7-23.5), nurses' listening (OR = 8.65,
      CI: 3.62-20.64), doctors' explanations (OR = 8.21, CI: 3.5-19.2), and attempts to
      control pain (OR = 7.71, CI: 3.22-18.46). Clinical factors and outcomes
      (complications, intensive care unit/hospital length of stay, mechanism of injury,
      and having an operation) were nonsignificant variables. For trauma patients,
      Injury Severity Score was inversely related to score (OR = 0.93, CI: 0.87-0.98).
      Insurance, education, and disposition were also tied to satisfaction, whereas
      age, gender, and ethnicity were nonsignificant. In conclusion, patient perception
      of interactions with the healthcare team was most strongly associated with
      satisfaction. Complications did not negatively influence satisfaction. Insurance
      status might potentially identify patients at risk of dissatisfaction. Listening
      to patients, treating them with respect, and explaining the care plan are
      integral to a positive perception of hospital stay. 

PMID- 25975344
TI  - A conflict between medical students on a surgical rotation.

PMID- 25975345
TI  - Small nucleolar RNA 78 promotes the tumorigenesis in non-small cell lung cancer.
AB  - BACKGROUND: Accumulating evidence suggests that dysregulated snoRNA may play a
      role in the development of malignancy. In the present study, we investigated the
      role of SNORD78 in the tumorigenesis of non-small cell lung cancer (NSCLC).
      METHODS: We determined the expression level of SNORD78 in NSCLC tissues with
      quantitative real-time PCR and then studied its clinical significance. We
      explored the biological significance of SNORD78 with gain-and-loss-of-function
      analyses both in vitro and in vivo. RESULTS: A great upregulation of SNORD78 was
      observed in cancer tissues compared to their adjacent normal tissues. Meanwhile,
      patients with high SNORD78 expression have significantly poorer prognosis than
      those with low expression. Inhibition of SNORD78 suppressed the proliferation of
      NSCLC cells via inducing G0/G1 cell cycle arrest and apoptosis while SNORD78
      overexpression promoted the cell proliferation. SNORD78 promoted invasion of
      NSCLC cells via inducing epithelial-mesenchymal-transition (EMT). SNORD78 was
      also obviously upregulated in cancer stem-like cells and is required for the self
      renewal of NSCLC. The oncogenic activity of SNORD78 was also confirmed with in
      vivo data. CONCLUSION: Our study identified that SNORD78 may be a potential
      therapeutic target for NSCLC.

PMID- 25975346
TI  - "We Have to Work Within the System!": Staff Perceptions of Organizational
      Barriers to Decision Making for Older Adults With Dementia in Australian Aged
      Care Facilities.
AB  - The current study explored the perceptions of direct care staff working in
      Australian residential aged care facilities (RACFs) regarding the organizational
      barriers that they believe prevent them from facilitating decision making for
      individuals with dementia. Normalization process theory (NPT) was used to
      interpret the findings to understand these barriers in a broader context. The
      qualitative study involved semi-structured interviews (N = 41) and focus groups
      (N = 8) with 80 direct care staff members of all levels working in Australian
      RACFs. Data collection and analysis were conducted in parallel and followed a
      systematic, inductive approach in line with grounded theory. The perceptions of
      participants regarding the organizational barriers to facilitating decision
      making for individuals with dementia can be described by the core category,
      Working Within the System, and three sub-themes: (a) finding time, (b) competing
      rights, and (c) not knowing. Examining the views of direct care staff through the
      lens of NPT allows possible areas for improvement to be identified at an
      organizational level and the perceived barriers to be understood in the context
      of promoting normalization of decision making for individuals with dementia.

PMID- 25975347
TI  - Medication Use Among Ethnically Diverse Older Adults in the United States.
AB  - As primary consumers of health care and prescription medication, older adults are
      more susceptible to potential drug-related adverse effects and medication
      interactions. With growing diversity among the older adult population,
      understanding ethnic differences in medication use becomes increasingly
      important. The current study describes polypharmacy and the occurrence of
      underprescribing among community-dwelling, low-income individuals 55 and older
      from four ethnic groups: (a) African American, (b) Afro-Caribbean, (c) European
      American, and (d) Hispanic American. Results revealed that number of illnesses,
      income level, and age were three major predictors associated with polypharmacy.
      No underprescription was identified. Overall, prevalence of polypharmacy was
      47.5%. European American individuals had the highest prevalence followed by
      Hispanic American, African American, and Afro-Caribbean individuals. When caring
      for older adults from various ethnic groups, nurses should focus their efforts on
      those who have multiple illnesses and sufficient income to purchase medications
      to reduce the risk of polypharmacy.

PMID- 25975348
TI  - Mechanism of Action for Nonpharmacological Therapies for Individuals With
      Dementia: Implications for Practice and Research.
AB  - The current review addresses the need for increased use of evidence-based,
      nonpharmacological therapies for individuals with dementia. To facilitate
      understanding of the potential efficacy of nonpharmacological therapies on
      cognitive functioning for individuals with dementia, the mechanisms of action for
      selected therapies are described, including the assessment method used to
      identify the mechanism. The strength of evidence supporting each therapy was
      evaluated, with some therapies demonstrating strong support and others only
      moderate support for their effectiveness and mechanism of action. Therapies with
      the strongest support include (a) cognitive training/stimulation, (b) physical
      exercise, and (c) music. Therapies with moderate support include (a) biofield,
      (b) meditation, (c) engagement with a naturally restorative environment, and (d)
      social engagement. Although the strength of evidence varies, together these
      therapies offer treatments designed to improve cognitive functioning, have low
      risks and adverse effects, and have the potential for widespread accessibility,
      thereby increasing the potential range of therapies for individuals with
      dementia.

PMID- 25975349
TI  - The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and
      BRCA2 mutant breast cancer cells.
AB  - PARP inhibitors are considered promising anticancer agents and currently being
      tested in clinical trials in hereditary breast cancer patients harboring
      mutations in BRCA1 and BRCA2 genes. In this study, we investigated the
      antiproliferative effects and mechanism of PARP inhibitors ABT-888 (Veliparib),
      BSI-201 (Iniparib) and AZD228 (Olaparib) in breast cancer cell lines with BRCA1
      or BRCA2 mutations and 9 different BRCA wild-type cell lines with BRCA1 allelic
      loss. We found that AZD2281 was the most potent in the PARP inhibitors and
      induces significant growth inhibition (~95%) in BRCA1 mutant (HCC-1937, MDA-MB
      436, and SUM-149PT) and BRCA2 mutant (HCC-1428) cell lines. AZD2281 treatment
      also resulted in growth inhibition ranging from 20 to 50% in cells with BRCA1
      allelic loss, including ER(+), HER2/Neu(+) and triple-negative breast cancer
      (TNBC) cells, but showed no effect in cells without with type BRCA without
      allelic loss. Knocking down of BRCA1 or BRCA2 in TNBC cells with BRCA1 allelic
      loss by RNA interference significantly enhanced AZD2281-induced growth inhibition
      and induced significant autophagy that was associated with mitophagy in cells
      with BRCA mutations. Inhibition of autophagy by gene knockdown significantly
      diminished AZD2281-induced mitophagy and apoptosis, indicating that autophagic
      process mediates some of the downstream effects of PARP inhibitors. In
      conclusion, our data provide the first evidence of PARP inhibitor AZD2281
      autophagy and mitophagy in breast cancer cell lines with BRCA mutations or BRCA
      allelic loss. In addition, our results indicate that the patients with BRCA1
      allelic loss may also benefit from PARP inhibitor therapy if BRCA is further
      inhibited.

PMID- 25975350
TI  - Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are Mediated
      Through Dual Inhibition of Ca(++) Influx and Phosphodiesterase Enzyme.
AB  - This study describes the antidiarrheal and antispasmodic activities of the hydro
      alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action
      explored along with activity-directed fractionation. Bp.Cr and its aqueous
      (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane
      (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in
      vivo and in-vitro assays. The crude extract (100-300 mg/kg) showed 20 and 60%
      protection of castor oil-induced diarrhea in mice. In isolated rabbit jejunum,
      Bp.Cr like papaverine inhibited spontaneous and high K(+) (80 mM)-induced
      contractions equi-potently. In guinea-pig ileum, Bp.Cr showed a moderate
      spasmogenic effect. The activity-directed fractionation revealed that the
      spasmolytic activity was concentrated in the organic fractions and spasmogenic
      component in the aqueous fraction. Amongst the organic fractions, BP.DCM and
      Bp.Pet inhibited spontaneous and high K(+) -induced contractions equi-potently,
      while Bp.But, like verapamil was more potent against high K(+) . The crude
      extract and its organic fractions caused rightward shift in the Ca(++) 
      concentration response curves (CRCs), similar to verapamil, and all except Bp.But
      potentiated the isoprenaline-inhibitory CRCs to the left, similar to papaverine.
      The results of this study indicate that the crude extract of B. polystachya
      possesses antidiarrheal and antispasmodic activities, mediated possibly through
      dual inhibition of Ca(++) influx and phospodiesterase enzyme.

PMID- 25975351
TI  - Differential Cellular Effects of Plk1 Inhibitors Targeting the ATP-binding Domain
      or Polo-box Domain.
AB  - The expression of polo-like kinase 1 (Plk1) correlates with malignancy and is
      thus recognized as a target for cancer therapy. In addition to the development of
      ATP-competitive Plk1 inhibitors, the polo-box domain (PBD), a unique functional
      domain of PLKs, is being targeted to develop Plk1-specific inhibitors. However,
      the action mechanisms of these two classes of Plk1 inhibitors have not been
      thoroughly evaluated. Here, we evaluate the differences in cellular effects of
      ATP-binding domain inhibitors (BI 2536, GSK 461364) and PBD inhibitors (poloxin,
      thymoquinone) to determine their mechanisms of Plk1 inhibition. Our data show
      that BI 2536 and GSK461364 increased the population of cells in the G2/M phase
      compared with controls, while treatment with poloxin and thymoquinone increased
      cell population in the S phase as well as in G2/M, in a p53-independent manner.
      The population of cells staining positively for p-Histone H3 and MPM2, mitotic
      index, was increased by treatment with BI 2536 or GSK461364, but not by treatment
      with poloxin or thymoquinone. Furthermore, treatment with BI 2536 or GSK461364
      resulted in activation of the BubR1 spindle checkpoint kinase, suggesting that
      treatment with ATP-binding domain inhibitors induces metaphase arrest. However,
      the administration of poloxin and thymoquinone resulted in an increase in
      p21(WAF1) and S arrest, indicating that PBD inhibitors also affected interphase
      before mitotic entry. Taken together, these data suggest that the PDB of Plk1
      plays a role in S phase progression through interaction with other proteins,
      while its ATP-binding domain is important for regulating mitotic progression
      mediated by its catalytic activity involving consumption of ATP.

PMID- 25975353
TI  - The geographic distribution of genetic diversity within gorillas.
AB  - Gorillas, like all non-human great apes, are endangered. Understanding the
      distribution of genetic diversity across their range is important because low
      diversity may arise in small populations through increased inbreeding, and, by
      reducing reproductive fitness, may lead to decreased chances of persistence of a
      given population. Previous studies found higher genetic diversity in the western
      (Gorilla gorilla) than in the eastern gorillas (Gorilla beringei), but rarely
      employed individuals of known geographic origin to investigate the distribution
      of diversity across multiple populations. The present study fills that gap by
      analyzing 1,161 individuals from nine sites across all four currently recognized
      Gorilla subspecies. Genetic diversity at each site was estimated using published
      data from seven highly-variable microsatellite loci. We found that the small and
      fragmented populations of Cross River gorillas, eastern lowland gorillas and
      mountain gorillas were less diverse than any of the five analyzed western lowland
      gorilla populations. The higher levels of genetic variation within the western
      lowland gorillas might be best explained by the facts that they (i) exhibit
      larger present and past effective population sizes than the other subspecies and
      (ii) maintain higher rates of gene flow through the existence of largely
      continuous habitat within their range. With regard to conservation, the high
      genetic diversity within western lowland gorillas is encouraging and retention of
      dispersal corridors between already protected areas is essential. Am. J.
      Primatol. 77:974-985, 2015. (c) 2015 Wiley Periodicals, Inc.

PMID- 25975352
TI  - A field camera for MR sequence monitoring and system analysis.
AB  - PURPOSE: MR image formation and interpretation relies on highly accurate dynamic
      magnetic fields of high fidelity. A range of mechanisms still limit magnetic
      field fidelity, including magnet drifts, eddy currents, and finite linearity and
      stability of power amplifiers used to drive gradient and shim coils. Addressing
      remaining errors by means of hardware, sequence, or signal processing
      optimizations, calls for immediate observation by magnetic field monitoring. The
      present work presents a stand-alone monitoring system delivering insight into
      such field imperfections for MR sequence and system analysis. METHODS: A flexible
      NMR field probe-based stand-alone monitoring system, built on a software-defined
      radio approach, is introduced and used to sense field dynamics up to third-order
      in space in a selection of situations with different time scales. RESULTS: Highly
      sensitive trajectories are measured and successfully used for image
      reconstruction. Further field perturbations due to mechanical oscillations and
      thermal field drifts following demanding gradient use and external interferences
      are studied. CONCLUSION: A flexible and versatile monitoring system is presented,
      delivering camera-like access to otherwise hardly accessible field dynamics with
      nanotesla resolution. Its stand-alone nature enables field analysis even during
      unknown MR system states.

PMID- 25975354
TI  - Survival benefit of levetiracetam in patients treated with concomitant
      chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma
      multiforme.
AB  - BACKGROUND: A chemosensitizing effect of levetiracetam (LEV) has been suggested
      because LEV inhibits O-6 methylguanine-DNA methyltransferase (MGMT). However, the
      survival benefit of LEV has not been clinically documented. The objective of this
      study was to assess the survival benefit of LEV compared with other antiepileptic
      drugs as a chemosensitizer to temozolomide for patients with glioblastoma.
      METHODS: In total, 103 consecutive patients with primary glioblastoma who
      received concomitant chemoradiotherapy and adjuvant chemotherapy with
      temozolomide were retrospectively reviewed, and 58 patients (56%) received LEV
      during temozolomide chemotherapy for at least 3 months. A Cox regression survival
      analysis was performed to adjust for confounding factors, including age, extent
      of lesion, Karnofsky performance scale score, extent of removal, and MGMT
      promoter methylation status. RESULTS: The median progression-free survival (PFS)
      and overall survival (OS) for patients who received LEV in combination with
      temozolomide (PFS: median, 9.4 months; 95% confidence interval [CI], 7.5-11.3
      months; OS: median, 25.7 months; 95% CI, 21.7-29.7 months) were significantly
      longer than those for patients who did not receive LEV (PFS: median, 6.7 months;
      95% CI, 5.8-7.6 months; OS: median, 16.7 months; 95% CI, 12.1-21.3 months; P =
      .010 and P = .027, respectively). In multivariate analysis, the variables that
      were identified as significant prognostic factors for OS were preoperative
      Karnofsky performance scale score (hazard ratio [HR], 0.37; P = .016), MGMT
      promoter methylation (HR, 0.30; P = .002), and receipt of LEV (HR, 0.31; P <
      .001. CONCLUSIONS: LEV may provide a survival benefit in patients with
      glioblastoma who receive temozolomide-based chemotherapy. A prospective
      randomized study may be indicated.

PMID- 25975355
TI  - Tick sialostatins L and L2 differentially influence dendritic cell responses to
      Borrelia spirochetes.
AB  - BACKGROUND: Transmission of pathogens by ticks is greatly supported by tick
      saliva released during feeding. Dendritic cells (DC) act as immunological
      sentinels and interconnect the innate and adaptive immune system. They control
      polarization of the immune response towards Th1 or Th2 phenotype. We investigated
      whether salivary cystatins from the hard tick Ixodes scapularis, sialostatin L
      (Sialo L) and sialostatin L2 (Sialo L2), influence mouse dendritic cells exposed
      to Borrelia burgdorferi and relevant Toll-like receptor ligands. METHODS: DCs
      derived from bone-marrow by GM-CSF or Flt-3 ligand, were activated with Borrelia
      spirochetes or TLR ligands in the presence of 3 MUM Sialo L and 3 MUM Sialo L2.
      Produced chemokines and IFN-beta were measured by ELISA test. The activation of
      signalling pathways was tested by western blotting using specific antibodies. The
      maturation of DC was determined by measuring the surface expression of CD86 by
      flow cytometry. RESULTS: We determined the effect of cystatins on the production
      of chemokines in Borrelia-infected bone-marrow derived DC. The production of MIP
      1alpha was severely suppressed by both cystatins, while IP-10 was selectively
      inhibited only by Sialo L2. As TLR-2 is a major receptor activated by Borrelia
      spirochetes, we tested whether cystatins influence signalling pathways activated
      by TLR-2 ligand, lipoteichoic acid (LTA). Sialo L2 and weakly Sialo L attenuated
      the extracellular matrix-regulated kinase (Erk1/2) pathway. The activation of
      phosphatidylinositol-3 kinase (PI3K)/Akt pathway and nuclear factor-kappaB (NF
      kappaB) was decreased only by Sialo L2. In response to Borrelia burgdorferi, the
      activation of Erk1/2 was impaired by Sialo L2. Production of IFN-beta was
      analysed in plasmacytoid DC exposed to Borrelia, TLR-7, and TLR-9 ligands. Sialo
      L, in contrast to Sialo L2, decreased the production of IFN-beta in pDC and also
      impaired the maturation of these cells. CONCLUSIONS: This study shows that DC
      responses to Borrelia spirochetes are affected by tick cystatins. Sialo L
      influences the maturation of DC thus having impact on adaptive immune response.
      Sialo L2 affects the production of chemokines potentially engaged in the
      development of inflammatory response. The impact of cystatins on Borrelia growth
      in vivo is discussed.

PMID- 25975356
TI  - Safety and efficacy of combined epidural/general anesthesia during major
      abdominal surgery in patients with increased intracranial pressure: a cohort
      study.
AB  - BACKGROUND: The increased intracranial pressure can significantly complicate the
      perioperative period in major abdominal surgery, increasing the risk of
      complications, the length of recovery from the surgery, worsening the outcome.
      Epidural anesthesia has become a routine component of abdominal surgery, but its
      use in patients with increased intracranial pressure remains controversial. The
      goal of the study was to evaluate the safety and efficacy of epidural anesthesia,
      according to monitoring of intracranial pressure in patients with increased
      intracranial pressure. METHODS: The study includes 65 surgical patients who were
      routinely undergone the major abdominal surgery under combined epidural/general
      anesthesia. Depending on the initial ICP all patients were divided into 2 groups:
      1 (N group) - patients with the normal intracranial pressure (<=12 mm Hg, n = 35)
      and 2 (E group) - patients with the elevated intracranial pressure (ICP > 12 mm
      Hg, n = 30). During the surgery we evaluated ICP, blood pressure, cerebral
      perfusion pressure (CPP). The parameters of recovery from anesthesia and the
      effectiveness of postoperative analgesia were also assessed. RESULTS: In N group
      ICP remained stable. In E group ICP decreased during anesthesia, the overall
      decline was 40% at the end of the operation (from 15 to 9 mm Hg (P <0.05)). The
      correction of MAP with vasopressors to maintain normal CPP was required mainly in
      patients with increased ICP (70% vs. 45%, p <0.05). CPP declined by 19% in N
      group. In E group the CPP reduction was 23%, and then it remained stable at 60 mm
      Hg. No significant differences in time of the recovery of consciousness,
      effectiveness of postoperative analgesia and complications between patients with
      initially normal levels of ICP and patients with ICH were noted. CONCLUSIONS: The
      combination of general and epidural anesthesia is safe and effective in patients
      with increased intracranial pressure undergoing elective abdominal surgery under
      the condition of maintaining the arterial pressure. Its use is not associated
      with the increase in intracranial pressure during the anesthesia, but it needs an
      intraoperative monitoring of ICP in order to prevent CPP reduction.

PMID- 25975357
TI  - Re: Pareek A, Chandurkar N, Thomas N, et al. Efficacy and safety of
      hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind,
      randomized comparison with pioglitazone. Curr Med Res Opin 2014;30:1257-66.

PMID- 25975358
TI  - PSYCHOLOGY IN FRENCH ACADEMIC PUBLISHING IN THE LATE NINETEENTH CENTURY: ALFRED
      BINET, EDITORIAL DIRECTOR AT THE SCHLEICHER PUBLISHING HOUSE.
AB  - To date, historians of psychology have largely ignored the role of academic
      publishing and the editorial policies of the late nineteenth century. This paper
      analyzes the role played by academic publishing in the history of psychology in
      the specific case of France, a country that provides a very interesting and
      unique model. Up until the middle of the 1890s, there was no collection
      specifically dedicated to psychology. Alfred Binet was the first to found, in
      1897, a collection of works specifically dedicated to scientific psychology. He
      chose to work with Reinwald-Schleicher. However, Binet was soon confronted with
      (1) competition from other French publishing houses, and (2) Schleicher's
      management and editorial problems that were to sound the death knell for Binet's
      emerging editorial ambitions. The intention of this paper is to encourage the
      efforts of the pioneers of modern psychology to have their work published and
      disseminated. 

PMID- 25975359
TI  - ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations
      and a detailed phenotype description.
AB  - ADAMTSL4 mutations seem to be the most common cause of isolated ectoplia lentis
      (EL) and thus are important concerning the differential diagnosis of connective
      tissue syndromes with EL as main feature. In this study, we describe an
      additional cohort of patients with apparently isolated EL. All underwent a
      detailed clinical exam with cardiac evaluation combined with ADAMTSL4 mutation
      analysis. Mutations were identified in 12/15 patients with EL. Besides the
      European founder mutation p. (Gln256Profs*38) we identified five further
      mutations not yet described in the literature: p. (Leu249Tyrfs*21), p.
      (Ala388Glyfs*8), p. (Arg746His), p. (Gly592Ser), and p. (Arg865His). Clinical
      evaluation showed common additional ocular features such as high myopia, but no
      major systemic findings. In particular: no dilatation of the aortic root was
      reported on. This report increases the total number of patients with ADAMTSL4
      mutations reported on today and reviews in detail the clinical findings in all
      patients reported on to date demonstrate, that these patients have a mainly
      ocular phenotype. There are no consistent systemic findings. The differentiation
      between syndromic and isolated EL is crucial for the further surveillance,
      treatment, and counseling of these patients, especially in young children.

PMID- 25975360
TI  - Robust relationship between reading span and speech recognition in noise.
AB  - OBJECTIVE: Working memory refers to a cognitive system that manages information
      processing and temporary storage. Recent work has demonstrated that individual
      differences in working memory capacity measured using a reading span task are
      related to ability to recognize speech in noise. In this project, we investigated
      whether the specific implementation of the reading span task influenced the
      strength of the relationship between working memory capacity and speech
      recognition. DESIGN: The relationship between speech recognition and working
      memory capacity was examined for two different working memory tests that varied
      in approach, using a within-subject design. Data consisted of audiometric results
      along with the two different working memory tests; one speech-in-noise test; and
      a reading comprehension test. STUDY SAMPLE: The test group included 94 older
      adults with varying hearing loss and 30 younger adults with normal hearing.
      RESULTS: Listeners with poorer working memory capacity had more difficulty
      understanding speech in noise after accounting for age and degree of hearing
      loss. That relationship did not differ significantly between the two different
      implementations of reading span. CONCLUSIONS: Our findings suggest that different
      implementations of a verbal reading span task do not affect the strength of the
      relationship between working memory capacity and speech recognition.

PMID- 25975361
TI  - Headspace solid-phase microextraction for wine volatile analysis.
AB  - The most commonly used technique to prepare samples for the analysis of wine
      volatile is the headspace solid-phase microextraction (HS-SPME). This method has
      gained popularity in last few years, as it is a unique solventless preparation
      technique. In this paper, a summary of recently published studies using HS-SPME
      for the analysis of wine aromas, with special emphasis on the method developed,
      has been compiled. Several papers are discussed in detail, mainly with respect to
      the SPME conditions used. A brief summary of the reviews related to HS-SPME
      analysis is given and discussed. Several parameters affecting the HS-SPME, such
      as the salt concentration and the agitation conditions, are used in the same way
      as used in several papers. The HS-SPME extraction proved to be sufficiently
      sensitive to satisfy legislative requirements related to low detection and
      quantification limits as well as method accuracy and precision requirements.
      However, in order to achieve the best performance and precision, the protocol
      needs to be optimized for each case. The effect of different parameters must be
      well characterized to ensure correct extraction and desorption to ensure the
      transfer of extracted compounds into the analytical system. The operating
      parameters, such as time, temperature, and agitation, must then be kept constant
      for all the samples.

PMID- 25975362
TI  - Ammonia quantitative analysis model based on miniaturized Al ionization gas
      sensor and non-linear bistable dynamic model.
AB  - In this paper, ammonia quantitative analysis based on miniaturized Al ionization
      gas sensor and non-linear bistable dynamic model was proposed. Al plate anodic
      gas-ionization sensor was used to obtain the current-voltage (I-V) data.
      Measurement data was processed by non-linear bistable dynamics model. Results
      showed that the proposed method quantitatively determined ammonia concentrations.

PMID- 25975363
TI  - Towards high efficiency air-processed near-infrared responsive photovoltaics:
      bulk heterojunction solar cells based on PbS/CdS core-shell quantum dots and TiO2
      nanorod arrays.
AB  - Near infrared (NIR) PbS quantum dots (QDs) have attracted significant research
      interest in solar cell applications as they offer several advantages, such as
      tunable band gaps, capability of absorbing NIR photons, low cost solution
      processability and high potential for multiple exciton generation. Nonetheless,
      reports on solar cells based on NIR PbS/CdS core-shell QDs, which are in general
      more stable and better passivated than PbS QDs and thus more promising for solar
      cell applications, remain very rare. Herein we report high efficiency bulk
      heterojunction QD solar cells involving hydrothermally grown TiO2 nanorod arrays
      and PbS/CdS core-shell QDs processed in air (except for a device thermal
      annealing step) with a photoresponse extended to wavelengths >1200 nm and with a
      power conversion efficiency (PCE) as high as 4.43%. This efficiency was achieved
      by introducing a thin, sputter-deposited, uniform TiO2 seed layer to improve the
      interface between the TiO2 nanorod arrays and the front electrode, by optimizing
      TiO2 nanorod length and by conducting QD annealing treatment to enhance charge
      carrier transport. It was found that the effect of the seed layer became more
      obvious when the TiO2 nanorods were longer. Although photocurrent did not change
      much, both open circuit voltage and fill factor clearly changed with TiO2 nanorod
      length. This was mainly attributed to the variation of charge transport and
      recombination processes, as evidenced by series and shunt resistance studies. The
      optimal PCE was obtained at the nanorod length of ~450 nm. Annealing is shown to
      further increase the PCE by ~18%, because of the improvement of charge carrier
      transport in the devices as evidenced by considerably increased photocurrent. Our
      results clearly demonstrate the potential of the PbS/CdS core-shell QDs for the
      achievement of high PCE, solution processable and NIR responsive QD solar cells. 

PMID- 25975364
TI  - The effect of anaesthetics on the properties of a lipid membrane in the
      biologically relevant phase: a computer simulation study.
AB  - Molecular dynamics simulations of the fully hydrated neat
      dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes
      containing four different general anaesthetic molecules, namely chloroform,
      halothane, diethyl ether and enflurane, have been simulated at two different
      pressures, i.e., at 1 bar and 1000 bar, at the temperature of 310 K. At this
      temperature the model used in this study is known to be in the biologically most
      relevant liquid crystalline (Lalpha) phase. To find out which properties of the
      membrane might possibly be related to the molecular mechanism of anaesthesia, we
      have been looking for properties that change in the same way in the presence of
      any general anaesthetic molecule, and change in the opposite way by the increase
      of pressure. This way, we have ruled out the density distribution of various
      groups along the membrane normal axis, orientation of the lipid heads and tails,
      self-association of the anaesthetics, as well as the local order of the lipid
      tails as possible molecular reasons of anaesthesia. On the other hand, we have
      found that the molecular surface area, and hence also the molecular volume of the
      membrane, is increased by the presence of any anaesthetic molecule, and decreased
      by the pressure, in accordance with the more than half a century old critical
      volume hypothesis. We have also found that anaesthetic molecules prefer two
      different positions along the membrane normal axis, namely the middle of the
      membrane and the outer edge of the hydrocarbon region, close to the polar
      headgroups. The increase of pressure is found to decrease the former, and
      increase the latter preference, and hence it might also be related to the
      pressure reversal of anaesthesia. 

PMID- 25975365
TI  - Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Signal via
      Phospholipase C Pathway to Block Apoptosis in Newborn Rat Retina.
AB  - Glutamate induced cell death mechanisms gained considerable attention lately as
      excessive release of extracellular glutamate was reported to cause
      neurodegeneration in brain areas including the retina. Conversely, pituitary
      adenylate cyclase-activating polypeptide (PACAP) was shown to provide
      neuroprotection through anti-apoptotic effects in the glutamate-model and also in
      other degeneration assays. Although PACAP is known to orchestrate complex
      intracellular signaling primarily through cAMP production, the mechanism that
      mediates the anti-apoptotic effect in glutamate excitotoxicity remains to be
      clarified. To study this mechanism we induced retinal neurodegeneration in
      newborn Wistar rats by subcutaneous monosodium-glutamate injection. 100 pmol
      PACAP and enzyme inhibitors were administered intravitreally. Levels of caspase
      3, 9, and phospho-protein kinase A were assessed by Western blots. Changes in
      cAMP levels were detected employing a competitive immunoassay. We found that cAMP
      blockade by an adenylyl-cyclase inhibitor (2',4'-dideoxy-adenosine) did not
      abrogate the neuroprotective effect of PACAP1-38. We show that following
      intravitreal PACAP1-38 treatment cAMP was unaltered, consistent with the
      inhibitor results and phospho-protein kinase A, an effector of the cAMP pathway
      was also unaffected. On the other hand, blockade of the alternative
      phosphatidylcholine-specific PLC pathway using an inhibitor (D609CAS) abrogated
      the neuroprotective effects of PACAP1-38. Our results highlight PACAP1-38 ability
      in protecting retinal cells against apoptosis through diverse signaling cascades.
      It seems that at picomolar concentrations, PACAP does not trigger cAMP
      production, but nonetheless, exerts a significant anti-apoptotic effect through
      PLC activation. In conclusion, PACAP1-38 may signal via both AC and PLC
      activation producing the same protective outcome. 

PMID- 25975367
TI  - (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are
      associated with PET/CT detection rate?
AB  - PURPOSE: To assess the association between PSA levels, PSA kinetics and other
      factors and a pathological (68)Ga-PSMA PET/CT scan in patients with recurrent
      prostate cancer (rPCa) with biochemical relapse (BR) after radical therapy.
      METHODS: Seventy consecutive rPCA patients referred for (68)Ga-PSMA PET/CT,
      matching all the following criteria, were retrospectively evaluated: (a) previous
      radical prostatectomy or primary radiotherapy with curative intent; (b) BR or
      persisting high PSA levels after primary treatment; and (c) complete clinical and
      imaging information. The mean +/- SD PSA level was 3.5 +/- 5.3 ng/mL (median 1.7,
      range 0.2 - 32.2 ng/mL), the mean +/- SD PSA doubling time (PSAdt) was 6.5 +/-
      5.5 months (median 5.5, range 1.3 - 31.6 months), and the mean +/- SD PSA
      velocity was 7.9 +/- 20.5 (median 2.1, range 0.2 - 147.5 ng/mL/year). Statistical
      analysis was performed to assess which factors were associated with the detection
      of rPCa on (68)Ga-PSMA PET/CT. RESULTS: (68)Ga-PSMA PET/CT was positive in 52 of
      70 patients (74.2%). In 30 patients (42.8%) lesions limited to the pelvis were
      detected. Distant lesions were observed in 8 of patients (11.4%). Local plus
      systemic lesions were detected in 14 patients (20%). PSA level (p = 0.017) and
      PSAdt (p = 0.0001) were significantly different between PET-positive patients
      (higher PSA level, shorter PSAdt) and PET-negative patients (lower PSA, longer
      PSAdt). ROC analysis showed that PSAdt 6.5 months and PSA 0.83 ng/mL were optimal
      cut-off values. In multivariate analysis PSAdt was associated with (68)Ga-PSMA
      PET/CT positivity. (68)Ga-PSMA PET/CT was positive in 17 of 20 patients (85%)
      with PSA <2 ng/mL and PSAdt <6.5 months, and in 3 of 16 patients (18.7%) with PSA
      <2 ng/mL and PSAdt >=6.5 months. CONCLUSION: The great potential of (68)Ga-PSMA
      PET/CT in patients with rPCa and BR was confirmed. PSA and PSAdt were valuable
      predictors of pathological (68)Ga-PSMA PET/CT findings.

PMID- 25975369
TI  - Wax Ester Analysis of Bats Suffering from White Nose Syndrome in Europe.
AB  - The composition of wax esters (WE) in the fur of adult greater mouse-eared bats
      (Myotis myotis), either healthy or suffering from white nose syndrome (WNS)
      caused by the psychrophilic fungus Pseudogymnoascus destructans, was investigated
      by high-resolution mass spectrometry analysis in the positive ion mode. Profiling
      of lipid classes showed that WE are the most abundant lipid class, followed by
      cholesterol esters, and other lipid classes, e.g., triacylglycerols and
      phospholipids. WE abundance in non-polar lipids was gender-related, being higher
      in males than in females; in individuals suffering from WNS, both male and
      female, it was higher than in healthy counterparts. WE were dominated by species
      containing 18:1 fatty acids. Fatty alcohols were fully saturated, dominated by
      species containing 24, 25, or 26 carbon atoms. Two WE species, 18:1/18:0 and
      18:1/20:0, were more abundant in healthy bats than in infected ones. 

PMID- 25975368
TI  - Prediction of prostate cancer recurrence using quantitative phase imaging.
AB  - The risk of biochemical recurrence of prostate cancer among individuals who
      undergo radical prostatectomy for treatment is around 25%. Current clinical
      methods often fail at successfully predicting recurrence among patients at
      intermediate risk for recurrence. We used a label-free method, spatial light
      interference microscopy, to perform localized measurements of light scattering in
      prostatectomy tissue microarrays. We show, for the first time to our knowledge,
      that anisotropy of light scattering in the stroma immediately adjoining cancerous
      glands can be used to identify patients at higher risk for recurrence. The data
      show that lower value of anisotropy corresponds to a higher risk for recurrence,
      meaning that the stroma adjoining the glands of recurrent patients is more
      fractionated than in non-recurrent patients. Our method outperformed the widely
      accepted clinical tool CAPRA-S in the cases we interrogated irrespective of
      Gleason grade, prostate-specific antigen (PSA) levels and pathological tumor-node
      metastasis (pTNM) stage. These results suggest that QPI shows promise in
      assisting pathologists to improve prediction of prostate cancer recurrence. 

PMID- 25975370
TI  - Action modes of recombinant endocellulase, EGA, and its domains on cotton
      fabrics.
AB  - OBJECTIVES: The action modes of an endocellulase, EGA, and its domains (CD9 and
      CBM3) during enzymatic treatment of cotton fabrics were investigated. RESULTS:
      EGA, CD9 and CBM3 had the binding capacity to cellulose substrates, of which the
      filter paper was the substrate with the strongest binding capacity. Analyses of
      scanning electronic microscopy indicated that EGA and its catalytic domain CD9
      etched the surface of cotton fabrics and broke the fibers of long chains. On the
      other hand, the binding domain CBM3 only resulted in swelling of cotton fibers.
      Both EGA and its catalytic domain CD9 had minimal effect on the weight loss of
      cotton fabrics, whereas the effect of EGA and CD9 on the degree of polymerization
      and breaking strength was significant. After 12 h enzymatic action, the values of
      weight loss ratio for EGA and CD9 were 2.07 and 2.21 %, respectively, meanwhile
      the reductions in fabric strength were 27.04 % for EGA and 17.23 % for CD9.
      CONCLUSIONS: In contrast to the action of EGA and CD9, CBM3 showed no significant
      changes in terms of the weight loss ratio, degree of polymerization, and fabric
      strength.

PMID- 25975371
TI  - Simple structured hybrid WOLEDs based on incomplete energy transfer mechanism:
      from blue exciplex to orange dopant.
AB  - Exciplex is well known as a charge transfer state formed between electron
      donating and electron-accepting molecules. However, exciplex based organic light
      emitting diodes (OLED) often performed low efficiencies relative to pure
      phosphorescent OLED and could hardly be used to construct white OLED (WOLED). In
      this work, a new mechanism is developed to realize efficient WOLED with extremely
      simple structure by redistributing the energy of triplet exciplex to both singlet
      exciplex and the orange dopant. The micro process of energy transfer could be
      directly examined by detailed photoluminescence decay measurement and time
      resolved photoluminescence analysis. This strategy overcomes the low reverse
      intersystem crossing efficiency of blue exciplex and complicated device structure
      of traditional WOLED, enables us to achieve efficient hybrid WOLEDs. Based on
      this mechanism, we have successfully constructed both exciplex-fluorescence and
      exciplex-phosphorescence hybrid WOLEDs with remarkable efficiencies. 

PMID- 25975372
TI  - Structural optimization of 3D-printed synthetic spider webs for high strength.
AB  - Spiders spin intricate webs that serve as sophisticated prey-trapping
      architectures that simultaneously exhibit high strength, elasticity and graceful
      failure. To determine how web mechanics are controlled by their topological
      design and material distribution, here we create spider-web mimics composed of
      elastomeric filaments. Specifically, computational modelling and microscale 3D
      printing are combined to investigate the mechanical response of elastomeric webs
      under multiple loading conditions. We find the existence of an asymptotic prey
      size that leads to a saturated web strength. We identify pathways to design
      elastomeric material structures with maximum strength, low density and
      adaptability. We show that the loading type dictates the optimal material
      distribution, that is, a homogeneous distribution is better for localized
      loading, while stronger radial threads with weaker spiral threads is better for
      distributed loading. Our observations reveal that the material distribution
      within spider webs is dictated by the loading condition, shedding light on their
      observed architectural variations. 

PMID- 25975373
TI  - Expression and clinical significance of hypoxia-inducible factor 1alpha, Snail
      and E-cadherin in human ovarian cancer cell lines.
AB  - The aim of the present study was to investigate the expression and clinical
      significance of hypoxia-inducible factor 1alpha (HIF-1alpha), Snail and E
      cadherin in ovarian cancer. The expression levels were assessed in a number of
      ovarian cancer cell lines and ovarian cancer tissues, and correlations between
      the expression of the three proteins and clinical pathological factors were
      analyzed. Transwell assays showed that the invasive ability of the ovarian cancer
      cell lines SKOV3 and ES-2 were significantly higher than those of TYK and 3AO
      (P<0.01). Furthermore, the expression levels of HIF-1alpha and Snail in SKOV3 and
      ES-2 were significantly higher than those in TYK and 3AO, whereas the expression
      levels of E-cadherin in SKOV3 and ES-2 were significantly lower than those in TYK
      and 3AO (P<0.05). In ovarian cancer tissues, the expression levels of HIF-1alpha,
      Snail and E-cadherin were correlated with clinical pathological factors (P<0.01);
      furthermore, there was a positive correlation between the expression levels of
      HIF-1alpha and Snail (r=0.231; P=0.021), and a negative correlation between the
      expression levels of Snail and that of E-cadherin (r=-0.225; P=0.028). HIF-1alpha
      was suggested to be able to suppress the expression of E-cadherin by upregulating
      Snail, thus serving an important role in invasion and metastasis of ovarian
      cancer.

PMID- 25975374
TI  - How well does Europe sleep? A cross-national study of sleep problems in European
      older adults.
AB  - OBJECTIVES: In this study, we aim to provide insight into the socio-demographic,
      family-related and socio-economic determinants of sleep problems in European
      older adults. METHODS: Data from the Survey of Health Ageing and Retirement in
      Europe (2011/2012) were used to perform multilevel logistic regression analyses
      on whether one has been bothered by sleep problems for at least 6 months. The
      final sample consisted of 54,722 respondents aged 50 and older from 16 countries.
      RESULTS: Prevalence rates varied from 16.6% in Denmark and Italy to 31.2% in
      Poland. The odds ratio of 2.014 confirmed a higher likelihood of sleep problems
      in women. People aged 60-69 (OR 0.898) reported less sleep problems than people
      between 50 and 59 years old. Finally, marriage compared to divorce and widowhood
      and having a higher socio-economic status were associated with less sleep
      problems. CONCLUSIONS: This study confirms sleep problems to be quite prevalent
      in the European older population. Increased awareness of the importance of sleep
      for health is needed, as well as further cross-national comparative research to
      explain the existing cross-country variation in sleep problems.

PMID- 25975375
TI  - Transcriptional events co-regulated by hypoxia and cold stresses in Zebrafish
      larvae.
AB  - BACKGROUND: Hypoxia and temperature stress are two major adverse environmental
      conditions often encountered by fishes. The interaction between hypoxia and
      temperature stresses has been well documented and oxygen is considered to be the
      limiting factor for the thermal tolerance of fish. Although both high and low
      temperature stresses can impair the cardiovascular function and the cross
      resistance between hypoxia and heat stress has been found, it is not clear
      whether hypoxia acclimation can protect fish from cold injury. RESULTS: Pre
      acclimation of 96-hpf zebrafish larvae to mild hypoxia (5% O2) significantly
      improved their resistance to lethal hypoxia (2.5% O2) and increased the survival
      rate of zebrafish larvae after lethal cold (10 degrees C) exposure. However, pre
      acclimation of 96-hpf larvae to cold (18 degrees C) decreased their tolerance to
      lethal hypoxia although their ability to endure lethal cold increased. RNA-seq
      analysis identified 132 up-regulated and 41 down-regulated genes upon mild
      hypoxia exposure. Gene ontology enrichment analyses revealed that genes up
      regulated by hypoxia are primarily involved in oxygen transport, oxidation
      reduction process, hemoglobin biosynthetic process, erythrocyte development and
      cellular iron ion homeostasis. Hypoxia-inhibited genes are enriched in inorganic
      anion transport, sodium ion transport, very long-chain fatty acid biosynthetic
      process and cytidine deamination. A comparison with the dataset of cold-regulated
      gene expression identified 23 genes co-induced by hypoxia and cold and these
      genes are mainly associated with oxidation-reduction process, oxygen transport,
      hemopoiesis, hemoglobin biosynthetic process and cellular iron ion homeostasis.
      The alleviation of lipid peroxidation damage by both cold- and hypoxia
      acclimation upon lethal cold stress suggests the association of these genes with
      cold resistance. Furthermore, the alternative promoter of hmbsb gene specifically
      activated by hypoxia and cold was identified and confirmed. CONCLUSIONS:
      Acclimation responses to mild hypoxia and cold stress were found in zebrafish
      larvae and pre-acclimation to hypoxia significantly improved the tolerance of
      larvae to lethal cold stress. RNA-seq and bioinformatics analyses revealed the
      biological processes associated with hypoxia acclimation. Transcriptional events
      co-induced by hypoxia and cold may represent the molecular basis underlying the
      protection of hypoxia-acclimation against cold injury.

PMID- 25975376
TI  - Caco-2 cells infected with rotavirus release extracellular vesicles that express
      markers of apoptotic bodies and exosomes.
AB  - Previously, we showed that infecting human intestinal epithelial cells (Caco-2)
      with rotavirus (RV) increases the release of extracellular vesicles (EVs) with an
      immunomodulatory function that, upon concentration at 100,000*g, present buoyant
      densities on a sucrose gradient of between 1.10 to 1.18 g/ml (characteristic of
      exosomes) and higher than 1.24 g/ml (proposed for apoptotic bodies). The effect
      of cellular death induced by RV on the composition of these EV is unknown. Here,
      we evaluated exosome (CD63, Hsc70, and AChE) and apoptotic body (histone H3)
      markers in EVs isolated by differential centrifugation (4000*g, 10,000*g, and
      100,000*g) or filtration/ultracentrifugation (100,000*g) protocols. When we
      infected cells in the presence of caspase inhibitors, Hsc70 and AChE diminished
      in EVs obtained at 100,000*g, but not in EVs obtained at 4000*g or 10,000*g. In
      addition, caspase inhibitors decreased CD63 and AChE in vesicles with low and
      high buoyant densities. Without caspase inhibitors, RV infection increased
      exosome markers in all of the EVs obtained by differential centrifugation.
      However, CD63 preferentially localized in the 100,000*g fraction and H3 only
      increased in EVs concentrated at 100,000*g and with high buoyant densities on a
      sucrose gradient. Thus, RV infection increases the release of EVs that, upon
      concentration at 100,000*g, are composed by exosomes and apoptotic bodies, which
      can partially be separated using sucrose gradients.

PMID- 25975377
TI  - Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers.
AB  - Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and
      anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours
      according to the current WHO Classification. Although the patients generally have
      longer survival as compared to those with glioblastoma, the timing of inevitable
      malignant progression ultimately determines the prognosis. Recent advances in
      molecular genetics have uncovered that histopathologically diagnosed astrocytomas
      may consist of two genetically different groups of tumours. The majority of
      diffusely infiltrating astrocytomas regardless of WHO grade have concurrent
      mutations of IDH1 or IDH2, TP53 and ATRX. Among these astrocytomas, no other
      genetic markers that may distinguish grade II and grade III tumours have been
      identified. Those astrocytomas without IDH mutation tend to have a distinct
      genotype and a poor prognosis comparable to that of glioblastomas. On the other
      hand, diffuse astrocytomas that arise in children do not harbour IDH/TP53
      mutations, but instead display mutations of BRAF or structural alterations
      involving MYB/MYBL1 or FGFR1. A molecular classification may thus help delineate
      diffusely infiltrating astrocytomas into distinct pathogenic and prognostic
      groups, which could aid in determining individualised therapeutic strategies. 

PMID- 25975379
TI  - Increase in telencephalic dopamine and cerebellar norepinephrine contents by
      hydrostatic pressure in goldfish: the possible involvement in hydrostatic
      pressure-related locomotion.
AB  - Fish are faced with a wide range of hydrostatic pressure (HP) in their natural
      habitats. Additionally, freshwater fish are occasionally exposed to rapid changes
      in HP due to heavy rainfall, flood and/or dam release. Accordingly, variations in
      HP are one of the most important environmental cues for fish. However, little
      information is available on how HP information is perceived and transmitted in
      the central nervous system of fish. The present study examined the effect of HP
      (water depth of 1.3 m) on the quantities of monoamines and their metabolites in
      the telencephalon, optic tectum, diencephalon, cerebellum (including partial
      mesencephalon) and vagal lobe (including medulla oblongata) of the goldfish,
      Carassius auratus, using high-performance liquid chromatography. HP affected
      monoamine and metabolite contents in restricted brain regions, including the
      telencephalon, cerebellum and vagal lobe. In particular, HP significantly
      increased the levels of dopamine (DA) in the telencephalon at 15 min and that of
      norepinephrine (NE) in the cerebellum at 30 min. In addition, HP also
      significantly increased locomotor activity at 15 and 30 min after HP treatment.
      It is possible that HP indirectly induces locomotion in goldfish via
      telencephalic DA and cerebellar NE neuronal activity. 

PMID- 25975380
TI  - Preclinical study of a novel hydrodynamically levitated centrifugal pump for long
      term cardiopulmonary support : In vivo performance during percutaneous
      cardiopulmonary support.
AB  - An extracorporeal centrifugal blood pump with a hydrodynamically levitated
      impeller was developed for use in a durable extracorporeal membrane oxygenation
      (ECMO) system. The present study examined the biocompatibility of the blood pump
      during long-term use by conducting a series of 30-day chronic animal experiments.
      The ECMO system was used to produce a percutaneous venoarterial bypass between
      the venae cavae and carotid artery in adult goats. No anticoagulation or
      antiplatelet therapy was administered during the experiments. Three out of four
      animals survived for the scheduled 30-day period, and the blood pumps and
      membrane oxygenators both exhibited sufficient hydrodynamic performance and good
      antithrombogenicity, while one animal died of massive bleeding from the outflow
      cannulation site. The animals' plasma free hemoglobin had returned to within the
      normal range by 1 week after the surgical intervention, and their hemodynamic and
      biochemistry parameters remained within their normal ranges throughout the
      experiment. The explanted centrifugal blood pumps did not display any trace of
      thrombus formation. Based on the biocompatibility demonstrated in this study, the
      examined centrifugal blood pump, which includes a hydrodynamically levitated
      impeller, is suitable for use in durable ECMO systems. 

PMID- 25975378
TI  - Dysregulation of locus coeruleus development in congenital central
      hypoventilation syndrome.
AB  - Human congenital central hypoventilation syndrome (CCHS), resulting from
      mutations in transcription factor PHOX2B, manifests with impaired responses to
      hypoxemia and hypercapnia especially during sleep. To identify brainstem
      structures developmentally affected in CCHS, we analyzed two postmortem neonatal
      lethal cases with confirmed polyalanine repeat expansion (PARM) or Non-PARM
      (PHOX2B?8) mutation of PHOX2B. Both human cases showed neuronal losses within the
      locus coeruleus (LC), which is important for central noradrenergic signaling.
      Using a conditionally active transgenic mouse model of the PHOX2B?8 mutation, we
      found that early embryonic expression (<E10.5) caused failure of LC neuronal
      specification and perinatal respiratory lethality. In contrast, later onset
      (E11.5) of PHOX2B?8 expression was not deleterious to LC development and
      perinatal respiratory lethality was rescued, despite failure of chemosensor
      retrotrapezoid nucleus formation. Our findings indicate that early-onset mutant
      PHOX2B expression inhibits LC neuronal development in CCHS. They further suggest
      that such mutations result in dysregulation of central noradrenergic signaling,
      and therefore, potential for early pharmacologic intervention in humans with
      CCHS. 

PMID- 25975381
TI  - Implementation of public policy on alcohol and other drugs in Brazilian
      municipalities: comparative studies.
AB  - One of the challenges with respect to public health and the abuse of alcohol and
      other drugs is to implement policies in support of greater co-ordination among
      various levels of government. In Brazil, policies are formulated by the
      Secretaria Nacional de Politicas sobre Drogas (SENAD - State Department for
      Policies on Drugs) and the Ministerio da Saude (MS - Ministry of Health). This
      study aims to compare implementation of policies adopted by SENAD and MS at the
      municipal level. Three municipalities were intentionally selected: Juiz de Fora
      having a larger network of treatment services for alcohol and drug users; Lima
      Duarte, a small municipality, which promotes the political participation of local
      actors (COMAD - Municipal Council on Alcohol and Drugs); and Sao Joao Nepomuceno,
      also a small municipality, chosen because it has neither public services
      specialised to assist alcohol and other drugs users, nor COMAD. Data collection
      was conducted through interviews with key informants (n = 19) and a review of key
      documents concerned with municipal policies. Data analysis was performed using
      content analysis. In Juiz de Fora, there are obstacles regarding the integration
      of the service network for alcohol and other drug users and also the articulation
      of local actors, who are predominant in the mental health sector. In Lima Duarte,
      while there is a link between local actors through COMAD, their actions within
      the local service network have not been effective. In Sao Joao Nepomuceno, there
      were no public actions in the area of alcohol and drugs, and consequently
      insufficient local debate. However, some voluntary, non-governmental work has
      been undertaken. There were weaknesses in the implementation of national-level
      policies by SENAD and the MS, due to the limited supply of available treatment,
      assistance and the lack of integration among local actors.

PMID- 25975382
TI  - Phototherapeutic Effect of Low-Level Laser on Thyroid Gland of Gamma-Irradiated
      Rats.
AB  - One inescapable feature of life on the earth is exposure to ionizing radiation.
      The thyroid gland is one of the most sensitive organs to gamma-radiation and
      endocrine disrupters. Low-level laser therapy (LLLT) has been used to stimulate
      tissue repair, and reduce inflammation. The aim of this study was to gauge the
      value of using Helium-Neon laser to repair the damaged tissues of thyroid gland
      after gamma-irradiation. Albino rats were used in this study (144 rats), divided
      into control, gamma, laser, and gamma plus laser-irradiated groups, each group
      was divided into six subgroups according to time of treatment (total six
      sessions). Rats were irradiated once with gamma radiation (6 Gy), and an external
      dose of laser (Wavelength 632.8 nm, 12 mW, CW, Illuminated area 5.73 cm(2), 2.1
      mW cm(-2) 120 s, 1.4 J, 0.252 J cm(-2)) twice weekly localized on thyroid region
      of the neck, for a total of six sessions. Animals were sacrificed after each
      session. Analysis included thyroid function, oxidative stress markers, liver
      function and blood picture. Results revealed improvement in thyroid function,
      liver function and antioxidant levels, and the blood cells count after LLLT.

PMID- 25975384
TI  - Flexible endoscopic treatment for Zenker's diverticulum with the SB Knife.
      Preliminary results from a single-center experience.
AB  - BACKGROUND AND AIM: Flexible endoscopic septum division is becoming a prominent
      treatment option for Zenker's diverticulum (ZD). Over the years, various
      techniques have been developed and many cutting tools have been tested with
      varying results. We report our experience with a recently designed, monopolar,
      rotating, scissor-shaped device (SB Knife). METHODS: Data on 31 consecutive
      patients that underwent flexible endoscopic treatment for ZD with the use of the
      SB Knife were retrieved. Dysphagia, regurgitation, and respiratory symptom
      severity before the procedure were graded. Procedure duration, rate of
      complications, symptom changes after the procedure and rate of relapsing patients
      during follow up were recorded. RESULTS: The procedure was carried out
      successfully in all patients. Median procedure time was 14 min. One case of late
      onset bleeding developed 1 week after the procedure, and was managed
      endoscopically. A significant symptom improvement was achieved (dysphagia: median
      score <3, median score >0, P < 0.001; regurgitation: median score <2, median
      score >0, P < 0.001; respiratory symptoms: median score <2, median score >0, P =
      0.009). Two patients had mild relapsing symptoms, respectively, after 4 and 9
      months from the procedure but refused further treatment. CONCLUSIONS: Endoscopic
      treatment of ZD using this new device is safe and efficient at short term follow
      up. No perforations were observed and there was a substantial reduction of
      symptoms after the treatment. Larger studies are needed to fully assess
      advantages of this new device for endoscopic treatment of ZD.

PMID- 25975383
TI  - Radiographers supporting radiologists in the interpretation of screening
      mammography: a viable strategy to meet the shortage in the number of
      radiologists.
AB  - BACKGROUND: An alternative approach to the traditional model of radiologists
      interpreting screening mammography is necessary due to the shortage of
      radiologists to interpret screening mammograms in many countries. METHODS: We
      evaluated the performance of 15 Mexican radiographers, also known as radiologic
      technologists, in the interpretation of screening mammography after a 6 months
      training period in a screening setting. Fifteen radiographers received 6 months
      standardized training with radiologists in the interpretation of screening
      mammography using the Breast Imaging Reporting and Data System (BI-RADS) system.
      A challenging test set of 110 cases developed by the Breast Cancer Surveillance
      Consortium was used to evaluate their performance. We estimated sensitivity,
      specificity, false positive rates, likelihood ratio of a positive test (LR+) and
      the area under the subject-specific Receiver Operating Characteristic (ROC) curve
      (AUC) for diagnostic accuracy. A mathematical model simulating the consequences
      in costs and performance of two hypothetical scenarios compared to the status quo
      in which a radiologist reads all screening mammograms was also performed.
      RESULTS: Radiographer's sensitivity was comparable to the sensitivity scores
      achieved by U.S. radiologists who took the test but their false-positive rate was
      higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and
      the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was
      1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in
      which a radiographer reads all mammograms first, and a radiologist reads only
      those that were difficult for the radiographer, was more cost-effective than a
      scenario in which either the radiographer or radiologist reads all mammograms.
      CONCLUSIONS: Given the comparable sensitivity achieved by Mexican radiographers
      and U.S. radiologists on a test set, screening mammography interpretation by
      radiographers appears to be a possible adjunct to radiologists in countries with
      shortages of radiologists. Further studies are required to assess the
      effectiveness of different training programs in order to obtain acceptable
      screening accuracy, as well as the best approaches for the use of non-physician
      readers to interpret screening mammography.

PMID- 25975385
TI  - Circumscribed cicatricial alopecia due to localized sarcoidal granulomas and
      single-organ granulomatous arteritis: a case report and systematic review of
      sarcoidal vasculitis.
AB  - Vasculitis associated with sarcoid granulomas is an uncommon phenomenon. A 72
      year-old female presented with an expanding region of circumscribed alopecia and
      scalp atrophy of 2 months duration. Biopsy showed non-caseating granulomas,
      dermal thinning, loss of follicles, fibrosis and muscular vessels disrupted by
      mixed lymphocyte, macrophage and giant-cell infiltrates. Affected vessels had
      loss and fragmentation of the elastic lamina, fibrous replacement of their walls
      and luminal stenosis (endarteritis obliterans). Dermal and vascular advential
      intralymphatic granulomas and lymphangiectases were found by D2-40 expression,
      suggesting lymphatic obstruction and poor antigen clearance. No evidence of a
      post-zoster eruption, systemic sarcoidosis or systemic giant-cell arteritis was
      found. Two years later, prednisone had halted - but not reversed - progression of
      her alopecia. Review of the literature showed two types of vasculitis associated
      with sarcoid granulomas: (i) acute, self-limited leukocytoclastic vasculitis and
      (ii) chronic granulomatous vasculitis (GV). Persistence of non-degradable
      material or antigen contributes to the pathogenesis of granulomatous
      inflammation. In this case, lymphatic obstruction probably impeded clearance of
      nonimmunologic and/or immunologic stimuli permitting and sustaining the
      development of sarcoid granulomas and sarcoid GV, ultimately causing scarring
      alopecia and cutaneous atrophy. 

PMID- 25975386
TI  - The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal
      symptoms in opioid-dependent volunteers.
AB  - Glial activation is hypothesized to contribute directly to opioid withdrawal.
      This study investigated the dose-dependent effects of a glial cell modulator,
      ibudilast, on withdrawal symptoms in opioid-dependent volunteers after abrupt
      discontinuation of morphine administration. Non-treatment-seeking heroin
      dependent volunteers (n = 31) completed the in-patient, double-blind, placebo
      controlled, within-subject and between-group study. Volunteers were maintained on
      morphine (30 mg, QID) for 14 days and placebo (0 mg, QID) for the last 7 days of
      the 3-week study. Volunteers also received placebo (0 mg, PO, BID) capsules on
      days 1-7. On days 8-21, volunteers were randomized to receive ibudilast (20 or 40
      mg, PO, BID) or placebo capsules. Subjective and clinical ratings of withdrawal
      symptoms were completed daily using daily using the Subjective Opioid Withdrawal
      Scale (SOWS) and Clinical Opioid Withdrawal Scale (COWS). Medication side effects
      were also monitored. Relative to the first 2 weeks, all groups exhibited
      withdrawal during the third week as assessed by the SOWS and COWS (P <= 0.0001).
      Although overall SOWS scores did not differ between groups, exploratory analyses
      pooling the two ibudilast groups demonstrated that they had lower ratings of
      withdrawal symptoms on SOWS items ('anxious,' 'perspiring,' 'restless,' 'stomach
      cramps') during detoxification relative to the placebo group. Ibudilast was well
      tolerated; no serious adverse events occurred during the study. Pharmacological
      modulation of glial activity with ibudilast decreased some subjective ratings of
      opioid withdrawal symptoms. These exploratory findings are the first to
      demonstrate the potential clinical utility of glial modulators for treating
      opioid withdrawal in humans.

PMID- 25975387
TI  - The efficacy of a health-related quality-of-life intervention during 48 weeks of
      biologic treatment of patients with moderate to severe psoriasis: results of a
      multicentre randomized controlled trial.

PMID- 25975388
TI  - The value of purpose built mental health facilities: Use of the Ward Atmosphere
      Scale to gauge the link between milieu and physical environment.
AB  - This study investigated changes in the 'atmosphere' of an acute adult mental
      health setting following relocation to a new purpose-built facility. The Ward
      Atmosphere Scale (WAS) was designed and validated for specific use in hospital
      based psychiatric facilities, and measures several dimensions of an environment.
      In this study, the WAS was administered to consumers and staff at periods before
      and also after their relocation to a new purpose-built acute adult mental health
      facility. There were significant improvements in the physical atmosphere of the
      new facility, when compared with the old facility. In terms of ward atmosphere,
      however, improvements were seen to occur in only a small number of measures and
      there were minor differences between consumers' and staff perspectives on some
      indicators. Interestingly, it was found that consumers noted less 'staff control'
      in the new setting, raising the question of the differences in understanding of
      control. For staff only, there was a perception of greater levels of consumer
      'involvement' in the new facility. Despite the minor differences in perception,
      the study does confirm that architecture is an important influence on the
      'atmosphere' of a health facility, for both staff and consumers. 

PMID- 25975389
TI  - Metformin targets Axl and Tyro3 receptor tyrosine kinases to inhibit cell
      proliferation and overcome chemoresistance in ovarian cancer cells.
AB  - Metformin, the most frequently prescribed anti-diabetic drug, has recently been
      paid attention as a chemotherapeutic agent. In this study, we demonstrated that
      metformin decreased the viability of parental as well as cisplatin/taxol
      resistant ovarian cancer cells. Its anti-proliferative effect was further
      demonstrated by dose-dependent reduction of the clonogenic ability of the
      metformin-treated cells. We next observed the effect of metformin on expression
      of Axl and Tyro3 receptor tyrosine kinases (RTKs) which belong to the TAM
      subfamily of RTKs transducing pro-survival and anti-apoptotic signals. Metformin
      treatment of ovarian cancer cells decreased both mRNA and protein levels of Axl
      and Tyro3 in a dose-dependent manner. Axl promoter activity was also inhibited by
      metformin, indicating that metformin suppresses Axl and Tyro3 expression at the
      transcriptional level. Metformin treatment was also found to augment its anti
      proliferative effect in SKOV3 and taxol-resistant SKOV3/TR cells transfected with
      Axl and Tyro3 specific siRNAs, siAxl and siTyro3, respectively, suggesting that
      metformin might target Axl and Tyro3 RTKs to restrain cell proliferation. In
      parallel, the level of X-linked inhibitor of apoptosis protein (XIAP), an anti
      apoptotic molecule, was reduced in the metformin-treated cells. Collectively, our
      data showed that metformin caused reduction of Axl and Tyro3 RTKs' expression,
      inactivation of downstream effectors, and decrease of anti-apoptotic protein
      level, forming a potent therapeutic strategy to facilitate its anticancer
      activity as well as to overcome chemoresistance in human ovarian cancer cells. 

PMID- 25975391
TI  - [Human struggle with infectious diseases will never end].

PMID- 25975392
TI  - [Analysis of morbidity and mortality characteristics of the notifiable diseases
      reported in 2013 in China].
AB  - OBJECTIVE: To learn the characteristics of morbidity and mortality of notifiable
      diseases reported in China in 2013. METHODS: Descriptive analysis method was used
      to analyze the morbidity and mortality of notifiable diseases in China in 2013,
      with Microsoft Excel 2010 and ArcGIS 10.0 used to develop statistical charts.
      RESULTS: In 2013, the morbidity of the nationwide notifiable diseases was
      473.87/100 000, a decrease of 3% below the average of the recent 3 years, while
      the mortality was 1.23/100 000, an increase of 2% over the average of the recent
      3 years. The rate of laboratory diagnosis of the reported cases was 38.4%. Top 5
      diseases of the reported incidence were hand foot and mouth disease, other
      infectious diarrhea, hepatitis B, tuberculosis and syphilis. The death cases
      reported were mainly AIDS, tuberculosis and rabies. As classified by the
      transmission route analysis, intestinal infectious diseases accounted for 49% of
      the total incidence reported for the year, followed by the blood and sexually
      transmitted infectious diseases, respiratory infectious diseases, animal and
      vector borne infectious diseases. According to the pathogenic analysis, virus
      infectious diseases accounted for 68% of the total cases, higher than bacterial
      infectious diseases and animal-borne/vector-borne infectious diseases. In
      Shanghai, Zhejiang and Jiangsu, human infection with avian influenza A (H7N9)
      virus was emerging, as epidemic situation of measles, dengue fever and
      brucellosis were on the rise significantly nationwide, while the morbidity of
      infectious diseases decreased, namely pulmonary tuberculosis, hepatitis B among
      others. Morbidity of the top 5 provinces for notifiable infectious diseases were
      Hainan, Guangxi, Guangdong, Xinjiang and Zhejiang, respectively. CONCLUSION: The
      proportion of laboratory confirmed cases among totals was still low in 2013. The
      morbidity of the infectious diseases was higher in western provinces and parts of
      south-eastern province, the mortality was higher in western provinces. The
      emerging human infection with avian influenza A (H7N9) virus, and the high
      epidemic of measles, dengue fever and brucellosis in some areas had caught the
      society concerns.

PMID- 25975390
TI  - Population pharmacokinetic-pharmacodynamic modeling and dosing simulation of
      propofol maintenance anesthesia in severely obese adolescents.
AB  - BACKGROUND: Optimal dosing of propofol to maintain appropriate anesthetic depth
      is challenging in severely obese (SO) adolescents. We previously reported that
      total body weight (TBW) is predictive of propofol clearance. This study was aimed
      at characterizing pharmacokinetics (PK) and pharmacodynamics (PD) of propofol in
      SO adolescents, using bispectral index (BIS), and toward developing PK/PD model
      based dosing guidelines. METHODS: A prospective PK/PD study was conducted in 26
      SO children and adolescents aged 9-18 years (body mass index 31-69 kg.m(-2)),
      undergoing surgery with intravenous propofol anesthesia clinically titrated by
      providers blinded to BIS. BIS data and propofol infusion schemes were recorded.
      Venous blood samples collected during and after propofol infusion were assayed
      for propofol concentrations. A propofol PK/PD model was developed using NONMEM
      and model-based simulations were performed to determine propofol dosing regimens
      targeting BIS of 50 +/- 10. RESULTS: A three-compartment PK model linked to a
      sigmoidal inhibitory Emax PD model by a first-order rate constant, adequately
      described the propofol concentration (n = 375) and BIS (n = 3334) data. TBW was
      the most predictive covariate for propofol clearance [CL (l.min(-1) ) = 1.65 *
      (TBW/70)(0.75)]. An effect-site propofol concentration of 3.19 MUg.ml(-1) was
      estimated for half-maximal effect, with no identifiable predictive covariates.
      The proposed maintenance dosing regimen targeted to a BIS of 50 +/- 10, based on
      our PK/PD model, was able to predict desired propofol concentrations and BIS in a
      representative obese teen when used in conjunction with accepted PK/PD models for
      children/obese adults (PK:Eleveld/PD: Cortinez), further supporting evidence for
      the dosing based on TBW. CONCLUSION: This is the first study to describe the
      PK/PD of propofol in SO adolescents. The proposed maintenance dosing regimen for
      propofol uses TBW in an allometric function as a dosing scalar, with an exponent
      of 0.75. Our results suggest no relevant effect of obesity on the propofol
      concentration-BIS relationship.

PMID- 25975393
TI  - [Analysis of epidemiology characteristics of norovirus among diarrheal
      outpatients in 27 provinces in China, 2009-2013].
AB  - OBJECTIVE: To investigate the epidemiology characteristics of norovirus among
      diarrheal outpatients in China. METHODS: Diarrhea cases were monitored at
      emergency/outpatient departments at 173 hospitals in 27 provinces of China, with
      clinical and epidemiological data, and fecal specimens collected and sent to 58
      network-laboratories to detect norovirus by RT-PCR method, and to analyze the
      positive rate of norovirus in various regions, population and time during 2009
      2013. RESULTS: 11.6% of the 34 031 diarrheal cases under surveillance were found
      with norovirus. Age group of 6-23 month-old children and that of people over 45
      years old were found with the highest positive percentage, 13.7% and 12.4%
      respectively. Positive percentage of norovirus peaks in autumn and winter in a
      year; it peaks in mid-temperate zones (10.7%) and warm-temperate zones (11.6%) in
      winter. It peaks in sub-tropical zones in autumn (14.3%). The most prevalent
      genogroups detected were norovirus G II, accounting for 89.9% of identified
      strains. CONCLUSION: Norovirus affects all ages and was most prevalent in
      children and the elderly among diarrhea outpatients. Norovirus' positive
      percentage showed strong seasonal pattern, and peaks at different times of a year
      in different climate zones of China. Since no effective preventive measures
      existed, further study on norovirus epidemiology and intervention strategies
      should be conducted in future.

PMID- 25975394
TI  - [Analysis of epidemiological features of human rabies in China, 2012].
AB  - OBJECTIVE: To analyze epidemiological characteristics and trends of rabies and
      explore control and prevention measures based on the rabies surveillance data of
      2012 in China. METHODS: Data of 2012 from China's infectious disease surveillance
      reporting and management system and sentinel surveillance systems in 6 provinces
      were used, for a retrospective analysis in descriptive epidemiological methods.
      RESULTS: 1 425 cases were reported in 731 counties of 27 provinces in 2012 and 1
      361 deaths were reported due to rabies, with the rabies incidence rate and
      mortality rate of 0.11/100 000 and 0.10/100 000 respectively, decreasing by 26.0%
      and 27.9% respectively from 2011. Rabies epidemic was mainly found in southern
      regions, followed by middle and eastern regions in China. 49.6% of total rabies
      cases were found in Guangxi, Guangdong, Hunan, Guizhou, and Henan province, which
      were the top five provinces. The rabies cases were mainly peasants, students and
      scattered children, accounting for 70.9%, 8.3% and 5.8% of total cases
      respectively. The male-female ratio in rabies cases was 2.6 : 1. In 2012, 294
      epidemiological questionnaires were collected, revealing that 92.1% of the
      exposure was caused by dogs and 6.8% by cats. The median of latent period was 70
      days. 62.4% of the cases were exposed in upper limb, and only 6.9% of such cases
      were vaccinated after exposure while the proportion of passive immunity
      biological vaccination was 2.9% for cases with exposure of category III.
      Surveillance data from PEP (post-exposure prophylaxis) clinics showed that 81.7%
      of the visitors were hurt by dogs and the exposure categories I, II and III
      accounted for 7.0%, 50.5% and 42.5% respectively. The proportion of of the
      exposure categories varied by PEP surveillance clinics. CONCLUSION: Despite
      continuing decrease of rabies cases in China in 2012, the number of counties
      (districts) affected fall relatively slow, with a tendency of rabies spreading to
      the western and northern regions in China. There were more rabies cases in rural
      areas than urban ones, and children and elderly people constitute the high-risk
      population. Animal reservoir of rabies was still dogs as before. Poor PEP and
      insufficient use of vaccination and passive immunity preparations were main
      causes for onset of human rabies.

PMID- 25975395
TI  - [Clinical characteristics of hospitalized cases of severe acute respiratory
      infection with laboratory-confirmed influenza and the risk factors analysis of
      influenza infection for children under 15 years old in ten provinces in China
      during 2009-2014].
AB  - OBJECTIVE: To identify clinical characteristics of hospitalized laboratory
      confirmed influenza cases of children under 15 years old, and their risk factors
      of influenza infection. METHODS: Analyzing the reports of hospitalized laboratory
      confirmed influenza cases of children under 15 years old who were detected by the
      sentinel surveillance systems in 10 provinces from December 2009 to June 2014.
      Such data as their demographic, medical history, clinical symptoms and signs,
      treatment and outcome were collected using questionnaires, with their clinical
      characteristics and their risk factors of influenza infection described. RESULTS:
      Of the 2 937 severe acute respiratory infection inpatients, 190 (6.5%) were
      laboratory-confirmed influenza cases. 123 (64.7%) of such confirmed cases were
      male, and 139 (73.2%) were children under 5 years old, with age median of 3.0
      years (IQR: 1.0-5.0 years). 20 (10.5%) of them had at least one chronic medical
      condition, mostly chronic cardiovascular disease (3.2%), immunosuppressive
      disease (3.2%), and cancer/tumor (2.6%). Most common clinical symptoms of the
      cases were fever (92.6%) and cough (88.8%), of which abnormal pulmonary
      auscultation (51.1%) and abnormal chest X-ray performance (36.1%) were the most
      common clinical signs. 29 cases (15.8%) had complications, of which pneumonia
      (15.3%) was most common. 16 cases (8.6%) used antiviral drugs, and 4 cases (2.2%)
      were admitted into ICU. Risk factor analysis suggested that age < 6 months (OR =
      0.406, 95% CI: 0.203-0.815) was a protective factor against influenza infection;
      and age 5-9 years old (OR = 2.535, 95% CI: 1.059-6.066) was a risk factor for
      influenza infection. CONCLUSION: Hospitalized laboratory-confirmed influenza
      cases were found mostly in children under 5 years old. Risk exposure for
      influenza infection varied among age groups.

PMID- 25975396
TI  - [Clinical characteristics of adult influenza inpatients in ten provinces in China
      and analysis of severe risk factors].
AB  - OBJECTIVE: To identity the clinical characteristics and severe case risk factors
      for the adult inpatient cases confirmed of influenza monitored by the sentinel
      surveillance system for severe acute respiratory infection (SARI) inpatient cases
      in ten provinces in China. METHODS: Epidemiology and clinical information surveys
      were conducted for adult cases (>= 15 year old) consistent with SARI case
      definition, who were monitored by SARI sentinel hospitals in ten cities in China
      from December 2009 to June 2014, with their respiratory tract specimens collected
      for influenza RNA detection. Adult SARI cases were classified into influenza
      inpatient group and outpatient group by the detection outcomes, analyzing their
      demographic information, clinical and epidemiology characteristics respectively,
      in addition to risk factors for severe inpatient cases. RESULTS: 3 071 adult SARI
      cases were recruited from ten hospitals, including 240 (7.8%) cases of laboratory
      confirmed influenza, most of them being A (H1N1) pdm2009 and A (H3N2) sub-types.
      Age M of the included influenza cases was 63 year old, 47.1% of them being >= 65
      seniors. 144 (60.0%) cases of the influenza inpatients suffered from at least one
      chronic underlying condition, and the proportion of emphysema (7.9%) was higher
      than non-influenza inpatient cases (3.8%), being statistically significant
      (chi(2) = 3.963, P = 0.047). 19.4% of the women of childbearing age infected of
      influenza were in pregnancy, and only 1.1% of the 240 influenza cases had been
      vaccinated against influenza. The proportion of sore throat and dyspnea found
      among influenza inpatients was higher than inpatients without influenza. 17.4% of
      the influenza cases were accepted into ICU for treatment, with no statistical
      significance with non-influenza inpatient cases (P = 0.160). 23.1% of the
      influenza inpatients received an antiviral drug therapy, a figure higher than the
      non-influenza inpatient cases (4.8%) (P < 0.001). 41.5% of the inpatients
      developed complications, with the proportion of viral pneumonia significantly
      higher than the non-influenza inpatient cases (P < 0.001). Asthma (RR = 15.200,
      95% CI: 1.157-199.633), immunosuppressive diseases (RR = 5.250, 95% CI: 1.255
      21.960), pregnancy (RR = 21.000, 95% CI: 1.734-254.275), time interval from onset
      to admission less 7 days (RR = 1.673, 95% CI: 1.071-2.614) were identified as
      risk factors of severely-ill influenza cases. CONCLUSION: It was found that adult
      influenza inpatients were mostly >= 65 year old seniors. The influenza
      vaccination rate among the influenza cases was very low, and antivirus drugs were
      used less than necessary. In this regard, influenza vaccination was recommended
      for high risk groups of pregnant women, seniors and chronic disease patients on
      annual basis, while influenza inpatients were advised to use antiviral drugs as
      early as possible.

PMID- 25975397
TI  - [Estimation of hospitalization rate of laboratory confirmed influenza cases in
      Jingzhou city, Hubei province, 2010-2012].
AB  - OBJECTIVE: To estimate the hospitalization rate of severe acute respiratory
      infection (SARI) cases attributable to influenza in Jingzhou city, Hubei province
      from 2010 to 2012. METHODS: SARI surveillance was conducted at four hospitals in
      Jingzhou city, Hubei province from 2010 to 2012. Inpatients meeting the SARI case
      definition and with informed consent were enrolled to collect their demographic
      information, clinical features, treatment, and disease outcomes, with their
      respiratory tract specimens collected for PCR test of influenza virus. RESULTS:
      From April, 2010 to September, 2012, 19 679 SARI cases enrolled were residents of
      Jingzhou, and nasopharyngeal swab was collected from 18 412 (93.6%) cases of them
      to test influenza virus and 13.3% were positive for influenza. During the three
      consecutive 2010-2012 flu seasons, laboratory-confirmed influenza was associated
      with 102 per 100 000, 132 per 100 000 and 244 per 100 000, respectively. As for
      the hospitalization rate attributable to specific type/subtype of influenza
      virus, 48 per 100 000, 30 per 100 000 and 24 per 100 000 were attributable to A
      (H3N2), A (H1N1) pdm2009, and influenza B, respectively in 2010-2011 season; 42
      per 100 000 [A (H3N2)] and 90 per 100 000 (influenza B) in 2011-2012 season; 90
      per 100 000 [A (H3N2)] and one per 100 000 [influenza B] from April, 2010 to
      September, 2012. SARI hospitalization caused by influenza A or B occurred both
      mainly among children younger than five years old, with the peak in children aged
      0.5 year old. CONCLUSION: Influenza could cause a substantial number of
      hospitalizations and different viral type/subtype result in different
      hospitalizations over influenza seasons in Jingzhou city, Hubei province.
      Children less than five years old should be prioritized for influenza vaccination
      in China.

PMID- 25975399
TI  - [Trends of vegetables and fruits consumption among Chinese adults aged 18 to 44
      years old from 1991 to 2011].
AB  - OBJECTIVE: To identify the trends of vegetables and fruits consumption among
      Chinese adults aged 18 to 44 years old from 1991 to 2011. METHODS: Twenty four
      hour dietary recall data from China Health and Nutrition Survey (1991, 1993,
      1997, 2000, 2004, 2006, 2009 and 2011) were used to identify the trends of
      vegetables and fruits consumption among Chinese between 18 and 44 years old.
      RESULTS: From 1991 to 2011, the proportion of daily consumption of vegetables
      rarely varied, while the vegetables intake declined significantly; and the
      proportion of daily consumption and intake of fruits kept increasing as follows.
      By 2011, the proportion of daily consumption and intake of vegetables and fruits
      among the respondents were 99.7%, 48.0%, 321.6 g/d, and 90.1 g/d respectively. A
      significant drop was found in the vegetables intake among the respondents against
      the vegetables intake as recommended by the Chinese dietary guidelines, up to
      50.2% in 2011; a significant rise was found in the fruits intake of the
      respondents against the fruits intake as recommended by the said guidelines, up
      to 17.4% in 2011. CONCLUSION: The average daily intake of vegetables and fruits
      of young and middle-aged residents (18-44 age group) in nine provinces in China
      was found lower than that recommended in the Chinese dietary guidelines; in view
      of the high proportion of people having less vegetables and fruits intake that
      those recommended by the Chinese dietary guidelines, further measures are
      expected to encourage their vegetables and fruits intake.

PMID- 25975398
TI  - [Investigation on the causes of increased hepatitis E cases reported in Guizhou
      province].
AB  - OBJECTIVE: To analyze causes of growing hepatitis E (HE) cases reported in
      Guizhou province, and probe into existing problems faced by medical institutions
      in diagnosis of clinical and laboratory-confirmed cases, for the purpose of
      improving the quality of HE surveillance system. METHODS: Six hospitals reporting
      greater HE cases from 2007 to 2011 were pinpointed, whose reported cases rose
      suddenly in 2011. Such cases were investigated by means of impatient medical
      record review, results of laboratory test and clinician interview. RESULTS: 136
      of the 354 reported HE cases investigated were found compliant with the
      diagnostic criteria of HE with an accordance rate of 38.42%. Difference of the HE
      diagnostic accordance rate among individual years, hospitals and reporting
      departments was statistically significant. Such rate of hospital reports was
      found to be the lowest in 2011, ranging from 0 to 18.18% respectively; HE cases
      reported by non-infectious departments accounted for 61.30% of total cases
      reported, with its accordance rate considerably below the infectious departments
      (8.29%). HE positive cases and HE positive rate in 2011 were significantly higher
      than that of preceding years. CONCLUSION: Such increase of reported HE cases in
      2011 in the province was mostly attributable to more HE laboratory tests made by
      the hospitals, yet the accordance rates were lower than satisfactory. In this
      regard, the medical institutions in question were advised to enhance their
      competency training for HE diagnosis and case report quality.

PMID- 25975400
TI  - [An assessment of association of thyroid volume with growth indicators and
      comparison of different thyroid volume indexes in school-aged children].
AB  - OBJECTIVE: To analyze the association between thyroid volume and physical growth
      of school-age children, and to compare volume indexes of individual thyroids for
      reference of selection of assessment indicators. METHODS: All the students of the
      12 classes of grades 3-5 at a primary school in Minhang district, Shanghai were
      rounded up with a multi-stage cluster sampling, for physical examinations to
      measure their height, weight, Body mass index (BMI) and body surface area (BSA),
      followed by B-ultrasonography to measure their thyroid volume. Data of the
      measurements were calculated to learn their height corrected volume index (HVI),
      weight and height corrected volume index (WHVI), BMI corrected volume (BMIV), and
      BSA corrected volume (BSAV) individually. Their urine and salt samples were
      collected to measure iodine concentration in urine and salt. Individual indexes
      were studied for their association with the growth and development indexes of
      children. RESULTS: Thyroid volume data were collected for 485 students, including
      258 boys (53.2%) and 227 girls (46.8%). Their height, weight, BMI and BSA were
      found to be positively correlated with their age (P < 0.05). For children of the
      same age group, their thyroid volume was also positively correlated with their
      physical development indexes. Of all the thyroid indexes, the difference between
      BSAV physical development factors had no statistical association (with partial
      correlation coefficients for age, gender, height, and weight being 0.07, 0.05,
      0.01 and 0.02 respectively), and their thyroid volume, HVI, BMI and weight were
      correlated to age, height and weight. CONCLUSION: Thyroid volume was associated
      with age and weight. It was inappropriate to diagnose goiter with criteria of
      age, gender and thyroid volume. BSAV was recommended for its non-association with
      age, gender and weight and its stability.

PMID- 25975401
TI  - [Competing risk model based study of outcomes of mild cognitive impairment of
      seniors].
AB  - OBJECTIVE: To introduce the competing risk model into outcome prediction of mild
      cognitive impairment (MCI) of seniors and to explore influencing factors for the
      prognosis of MCI to Alzheimer's disease (AD). METHODS: Data were collected from
      six follow-up visits to 600 seniors from communities in Taiyuan city, which were
      conducted at an interval of six months from October 2010 to May 2013. MCI state
      was defined as the transient state, AD and death before AD as two absorbing
      states (death before AD in which was regarded as a competing risk event),
      building the competing risk model to identify the model parameters, and to
      explore influencing factors on MCI prognosis to AD. In the meantime, the 3-year
      MCI-AD transition probability was estimated based on the multi-state Markov
      model. RESULTS: Based on screening with the multivariate competing risk model
      analysis, factors such as higher age (estimate HR = 1.56, 95% CI: 1.01-2.39),
      female gender (HR = 1.72, 95% CI: 1.02-2.92), higher education (HR = 0.64, 95%
      CI: 0.41-1.00), reading frequently (HR = 0.57, 95% CI: 0.32-0.99), hypertension
      (HR = 3.43, 95% CI: 1.08-10.85) and high SBP (HR = 1.67, 95% CI: 1.04-2.66), were
      statistically significant for transition from MCI to AD in three years. 3-year
      MCI-AD transition probability was 10.7% (95% CI: 8.6%-13.2%). CONCLUSION: Age,
      gender, education, reading and blood pressure were the influencing factors for
      the prognosis of MCI to AD. Competing risk model was advantageous in studying
      longitudinal data with multiple potential outcomes.

PMID- 25975402
TI  - [HIV/AIDS related mortality in southern Shanxi province and its risk factors].
AB  - OBJECTIVE: To explore factors influencing mortality rate of HIV/AIDS and to
      improve the effectiveness of antiretroviral therapy (ART). METHODS: By means of
      retrospective cohort study and the AIDS control information system, HIV/AIDS case
      reports and antiviral treatment information of 4 cities in southern Shanxi
      province up to end of December 2012 were selected, to calculate the mortality
      rate and treatment coverage based on further data collected, along with analysis
      using the Cox proportional hazards survival regression. RESULTS: 4 040 cases
      confirmed of HIV/AIDS were included in this study. The average age was (36.0 +/-
      12.9) years, with 65.3% being male, 56.5% being married, 73.5% having junior high
      school education or lower, 58.4% being peasants, 54.3% with sexually transmitted
      infection (40.1% were heterosexual, 14.2% were homosexual), and 38.9% were
      infected via blood transmission (20.2% were former plasma donors, 16.2% blood
      transfusion or products recipients, 2.4% were injection drug users). Overall
      mortality decreased from 40.2 per 100 person/year in 2004 to 6.3 per 100
      person/year in 2012, with treatment coverage concomitantly increasing from almost
      14.8% to 63.4%. Cox proportional hazards survival regression was used on 4 040
      qualified cases, demonstrating the top mortality risk factor was without
      antiretroviral therapy (RR = 14.9, 95% CI: 12.7-17.4). Cox proportional hazards
      survival regression was made on 1 938 cases of antiviral treatment, demonstrating
      that the mortality risk of underweight or obese before treatment was higher than
      those of normal and overweight cases (RR = 2.7, 95% CI: 1.6-4.5), and the
      mortality of those having a CD4(+) T-lymphocyte count <= 50 cells per ul before
      treatment was more than 50 cases (RR = 2.6, 95% CI: 1.5-4.5); Cox proportional
      hazards survival regression was made on 2 102 cases of untreated cases,
      demonstrating the mortality risk of those initially diagnosed as AIDS was higher
      than those initially diagnosed as HIV (RR = 3.4, 95% CI: 2.9-4.0). CONCLUSION:
      The ART could successfully make lower HIV/AIDS mortality rate, indicating
      effective ART can further decrease mortality.

PMID- 25975403
TI  - [Influencing factors for loss to follow-up in a longitudinal study on HIV
      incidence of female sex workers].
AB  - OBJECTIVE: To study the loss to follow-up (LTF) rate, HIV emerging incidence and
      influencing factors in the longitudinal study of female sex workers (FSWs) in
      Kaiyuan, Yunnan, and their influence on HIV emerging incidence estimate. METHODS:
      The open cohort study on FSWs was launched in March 2006 and ended in June 2013
      in Kaiyuan, Yunnan. Investigations were made every six months and lasted for 7
      years. 661 FSWs found as HIV negative in the baseline study in March 2006 were
      chosen to study their LTF in the 7 year follow-up investigation. The Cox
      regression model was used to explore risk factors for HIV emerging infection and
      those for LTF. In June 2013, a survey was also conducted to explore the detailed
      reasons for loss to follow-up by contacting FSWs themselves. RESULTS: During 1
      238.5 person-years of follow-up among 661 HIV negative FSWs, the HIV incidence
      rate was 1.29 (95% CI: 0.74-2.10)/100 person-year, and the LFT incidence rate was
      48.68 (95% CI: 44.88-52.73) /100 person-year. The multivariate analysis showed
      drug abuse as an independent risk factor for FSWs' infection of HIV (adjusted
      risk ratio = 4.15, 95% CI: 1.43-12.02); FSWs over 25 years old (adjusted risk
      ratio = 0.68, 95% CI: 0.57-0.81), and drug abuse (adjusted risk ratio = 0.52, 95%
      CI: 0.35-0.79) were found with lower LFT rate to remain in the cohort.
      CONCLUSION: High LFT rate was found in FSW cohort study in Kaiyuan, Yunnan, while
      the HIV infection risk exposure of the LFT group was lower than the groups of HIV
      follow-up. HIV prevalence of FSWs in the city might be overestimated. Causes of
      LFT of FSWs group required further study in the future, and the cohort follow-up
      retention strategy for FSWs needs to be developed.

PMID- 25975404
TI  - [Risky sexual transmission behavior and its influencing factors among HIV
      positive MSM population in Shanghai and Chengdu in China].
AB  - OBJECTIVE: To investigate the sexual transmission behaviors among HIV-positive
      MSM population engaging in unprotected sexual behaviors, as well as the
      relationship with health conditions and partner notification. METHODS: A total of
      308 HIV-positive MSM participants engaged in unprotected sexual behaviors were
      recruited by "snowballing" sampling in Shanghai and Chengdu. The questionnaire
      covered such items as the time of HIV infection diagnosis, CD4+ T cells count,
      viral load, antiviral therapy, anxiety and depressive symptoms, sexual partner
      types and sexual behaviors in the past six months, disclosure to fixed sexual
      partners and casual sexual partners among others. RESULTS: Of the 308
      participants surveyed, the report rate of those having at least one-time sexual
      transmission behaviors during the past 6 months was 70.1% (216/308). Participants
      who had primary sexual partners and casual sexual partners following their HIV
      infection diagnosis accounted for 89.0% (274/308) and 68.2% (210/308)
      respectively. Of the aforementioned participants, 59.1% (162/274) and 94.3%
      (198/210) respectively had not disclosed their HIV infection to primary and
      casual sexual partners. Of thoes who did not disclose their HIV infection to
      primary sexual partners, 91.9% (147/162) reported sexual transmission behaviors.
      Of thoes who did not disclose their HIV infection to casual sexual partners,
      89.9% (178/198) continue sexual transmission. As found in a multi-factor
      analysis, the infection risk exposure of those with heterosexual sexual
      orientation and engagement in sexual transmission behaviors was six times higher
      than those with homosexual orientation (aOR = 5.896, 95% CI: 1.808-19.232). For
      those who did not, or partially disclose their HIV infection to male casual
      sexual partners or commercial sexual partners, the risk exposure of further
      transmission was 29 times and 19 times higher than those disclose it to their
      sexual partners (no disclosure: aOR = 28.957, 95% CI: 7.511-65.004; partial
      disclosure: aOR = 18.956, 95% CI: 6.995-57.417). The highest risk came from those
      who continue their sexual transmission behavior within six months of their HIV
      infection diagnosis; the lowest risk came from those continue such behavior more
      than one year and within two years of their diagnosis (aOR = 0.048, 95% CI: 0.033
      0.788); such risk rose to some extent for those continue such behavior over two
      years of their diagnosis. Compared to those without antiviral therapy,
      participants with the therapy pose less risk in sexual transmission behaviors.
      CONCLUSION: More than two-thirds of HIV-positive MSM population who engage in
      unprotected sexual behaviors reported sexual transmission behaviors. In this
      regard, increasing antiviral therapy and promoting sexual partner disclosure
      constituted an effective strategy to minimize further transmission among HIV
      positive MSM population. Intervention of sexual transmission behaviors should be
      addressed to those diagnosed of HIV infection within six months.

PMID- 25975405
TI  - [Distribution trends and characteristics analysis of non-motor road traffic
      injury cases monitored in China, 2006-2013].
AB  - OBJECTIVE: To describe the distribution characteristics of outpatient/emergency
      cases of non-motor road traffic injuries in China from 2006-2013. METHODS: Cases
      of non-motor road traffic injuries were descriptively analyzed based on their
      data at the sentinel hospitals of the Chinese National Injury Surveillance System
      (NISS) from 2006 to 2013. RESULTS: The proportion of non-motor road traffic
      injuries among the total road traffic injuries of the year from 2006 to 2011 was
      relatively stable, and the proportion in 2013 was higher than 2012 (chi2 =
      508.138, P < 0.001). In the non-motor road traffic injuries cases in 2013, male
      cases were higher than females (chi2 = 41.018, P < 0.001), mostly found in 15 to
      64 years old age groups. In urban areas, the proportion of non-motor road traffic
      injuries cases (52.11%) was higher than rural areas (47.89%) (chi2 = 88.427, P <
      0.001). Most injuries were found in lower limbs (29.08%) and head (24.82%).
      Injuries were mainly bruises (73.54%) and fractures (10.72%). The severities of
      injuries were mainly mitigated injury (80.49%), and most injuries ended with home
      return following treatment (82.34%). CONCLUSION: The proportion of non-motor road
      traffic injuries among total road traffic injuries of the year as found from NISS
      remained stable from 2006 to 2011, with a slight rise in 2012-2013. Most of the
      non-motor road traffic injuries were suffered by young and middle aged men.
      Interventions should be made based on gender and age differences of non-motor
      road traffic injuries cases.

PMID- 25975406
TI  - [Analysis of follow-up and administration of HIV-infected Burmese in Dehong
      prefecture of Yunnan province].
AB  - OBJECTIVE: To compare follow-up and administration of HIV-infected local Chinese
      and Burmese in Dehong prefecture of Yunnan province, for scientific development
      of prevention and control measures. METHODS: 14 270 HIV-infected local Chinese
      and 5 436 HIV-infected Burmese reported from 1989 to December 31, 2013 in Dehong
      prefecture were recruited as the subjects of study, comparing the differences of
      follow-up and management, CD4+ T lymphocyte count tests and antiretroviral
      therapy (ART) between the two groups. RESULTS: The proportion of HIV-infected
      Burmese identified in Dehong prefecture was 27.6% (5 436/19 706) during 1989
      2013. The number had been growing rapidly from 17.1% in 1989-2003, 12.4% in 2004
      and 14.7% in 2005 to over 51.4% in 2012, hitting 59.4% in 2013 (trends chi2 = 1
      732.84, P < 0.000 1). The proportion of HIV-infected Burmese among case reports
      of various characteristics kept rising over the years. By the end of 2013, 8 095
      HIV-infected local Dehong residents and 5 326 HIV-infected Burmese were still
      alive. 95.8% of them were under follow-up, 88.5% having CD4+ T lymphocyte count
      tests, and 78.3% under ART. Among the HIV-infected B urmese, only 19.2% of them
      were under follow-up, 13.0% having CD4+ T lymphocyte count tests, and 6.1% under
      ART, significantly lower than the local Dehong residents (P < 0.000 1).
      CONCLUSION: The proportion of follow-up and administration, CD4+ T lymphocyte
      count tests, and ART of HIV-infected Burmese was low in Dehong prefecture, Yunnan
      province, which called for more effective follow-up and administration measures.

PMID- 25975407
TI  - [The epidemiology and etiology research of Tibetan sheep plague in Qinghai
      plateau].
AB  - OBJECTIVE: To identify the epidemiology and etiology characteristics of Tibetan
      sheep plague in Qinghai plateau. METHODS: The background materials of Qinghai
      Tibetan sheep plague found during 1975 to 2009 were summarized, the regional,
      time and interpersonal distribution, infection routes, ecological factors for the
      spread were used to analyze; followed by choosing 14 Yersinia pestis strains
      isolated from such sheep for biochemical test, toxicity test, virulence factors
      identification, plasmid analysis, and DFR genotype. RESULTS: From 1975 to 2009,
      14 Yersinia pestis strains were isolated from Tibetan sheep in Qinghai province.
      Tibetan sheep, as the infection source, had caused 10 cases of human plague, 25
      plague patients, and 13 cases of death. All of the initial cases were infected
      due to eating Tibetan sheep died of plague; followed by cases due to contact of
      plague patients, while all the initial cases were bubonic plague. Cases of
      bubonic plague developed into secondary pneumonic plague and septicemia plague
      were most popular and with high mortality. Most of the Tibetan sheep plague and
      human plague occurred in Gannan ecological zone in southern Gansu province, which
      was closely related to its unique ecological and geographical landscape. Tibetan
      sheep plague coincided with human plague caused by Tibetan sheep, especially
      noteworthy was that November (a time for marmots to start their dormancy)
      witnesses the number of Yersinia pestis strains isolated from Tibetan sheep and
      human plague cases caused by Tibetan sheep. This constituted the underlying cause
      that the epidemic time of Tibetan sheep plague lags obviously behind that of the
      Marmot plague. It was confirmed in the study that all the 14 strains were of
      Qinghai-Tibet Plateau ecotype, with virulence factors evaluation and toxicity
      test demonstrating strains as velogenic. As found in the (Different Region) DFR
      genotyping, the strains isolated from Yushu county and Zhiduo county were
      genomovar 5, the two strain isolated from Nangqian county were genomovar 5 and
      genomovar 7, while those isolated Delingha region were genomovar 8. CONCLUSION:
      Tibetan sheep were vulnerable to plague infection, hence causing human plague as
      the infectious source. The Yersinia pestis strains isolated from Tibetan sheep
      plague carried pathogen characteristics of Qinghai-Tibet plateau plague,
      developing many new characteristics of such plague.

PMID- 25975408
TI  - [Cloning and expression and preliminary antigenicity identification for the
      diagnostic antigen of hepatitis E virus].
AB  - OBJECTIVE: To clone, express and purify thioredoxin (named as N5), a specific
      diagnostic antigen of hepatitis E virus (HEV), and to initially evaluate its
      antigenicity and serological test performance. METHODS: Based on the gene
      sequences of HEV-ORF2 and carboxyl terminal ORF3 on GenBank, the codon was
      optimized by the Escherichia coli codon preference, inserted it into prokaryotic
      expression vector M48 following total gene synthesization, and expressed in
      Escherichia coli fusion protein N5 recombined with Thioredoxin (TRX). Fusion
      protein was purified in affinity chromatography, evaluating its antigenicity with
      Western blot technology, then evaluating its serological test performance using
      the negative and positive serum samples confirmed of HEV infection with
      laboratory and clinical tests. RESULTS: The recombinant plasmid expressing N5
      diagnostic antigen was successfully established; high-level expression and
      purification to obtain soluble diagnostic antigens; Western blot results
      indicating fusion protein N5 can be bound specifically with the serum of HEV IgM
      antibody positive, showing satisfactory antigencity; using fusion protein N5 as
      the capture antigen to build indirect ELISA, testing 40 serum samples of HEV
      cases confirmed by pathogen detection and clinical diagnosis and 40 serum samples
      of healthy people, with the sensitivity and specificity of 95% (38/40) and 90%
      (36/40) respectively. CONCLUSION: Recombinant plasmid expressing the HEV
      diagnostic antigen recombined with thioredoxin was successfully established, and
      soluble fusion protein N5 was obtained with high expression and strong
      antigenicity, promising in its future applications.

PMID- 25975409
TI  - [Etiology and molecular-epidemiological characteristics of viral
      meningoencephalitis of Zhejiang province in 2013].
AB  - OBJECTIVE: To investigate pathogens and molecular-epidemiology characteristics of
      viral meningoencephalitis in the monitoring sites of Zhejiang province, 2013.
      METHODS: Cerebrospinal fluid and/or stool specimens were collected from suspected
      patients admitted to the monitoring hospitals in southern and northern Zhejiang
      province. Such specimen were subject to real-time qPCR for the detection of Human
      enterovirus (HEV), Japanese encephalitis virus (JEV), Mumps virus (MuV), Herpes
      simplex virus (HSV) and Cytomegalovirus (CMV). HEVs were isolated using the RD
      and Hep-2 cell lines, while VP1 genes from all HEV-positive isolates or RNA
      positive specimen were amplified, sequenced, for homology and evolution analysis.
      RESULTS: 92 (38.5%) of the 239 samples collected from 229 patients were detected
      as virus nucleic acid positive, including 87 HEV positive samples, 1 MuV
      positive, 2 HSV positive, and 2 CMV positive; of the 87 HEV positive samples, 38
      were further determined to be Coxsackievirus (CV) and 49 as Echovirus (E). 56 HEV
      strains were isolated from 239 (23.4%) samples. From the 31 cerebral fluid
      specimen of nucleic acid positive yet virus isolation negative, the most specimen
      were identified with E9 (9 specimen), followed by CVA9 (8 specimen); the viral
      serotype of Zhejiang province HEV were CVA9, CVB4, CVB5, E6, E7, E9, E11, E14,
      E16, E25 and E30, respectively. Predominant epidemic strains identified at
      southern and northern Zhejiang province were CVB5 and E6 respectively. The
      phylogenetic analysis of VP1 gene showed that all the HEV isolates in Zhejiang
      province were HEV-B. CONCLUSION: The HEV-B was the main pathogen for viral
      meningoencephalitis in Zhejiang province in 2013, including 11 serotypes, while
      E7 was the first time to be isolated in Zhejiang province. The predominant
      isolates were CVB5 and E6 in southern and northern Zhejiang province
      respectively. The positive rate of viral nucleic acid detection was significantly
      higher than that of viral isolation. Regular EV isolation method was exposed to
      the risk of missing-detection of E9 and CVA9.

PMID- 25975411
TI  - [Exploring for theoretical system of field epidemiology as a discipline].

PMID- 25975410
TI  - [Study of molecular characteristics of methicillin-resistant Staphylococcus
      aureus in Maanshan area].
AB  - OBJECTIVE: To identity the distribution of enterotoxin and hemolysin, as well as
      the clonal complexes and drug resistance of the strains of methicillin-resistant
      Staphylococcus aureus (MRSA) in Maanshan region. METHODS: Automatic enzyme-linked
      fluorescent assay system and PCR technology were used to identify the
      distribution of enterotoxin and hemolysin genes. Seven Staphylococcus aureus
      hourskeeping genes were choosed as the target genes for multilocus sequence
      typing (MLST) on 34 strains of MRSA and 3 strains of methicillin-sensitive
      Staphylococcus aureus (MSSA), comparing the data with the online database and
      obtaining the sequence typing (ST), conducting affinity analysis on its ST based
      on eBURST, testing in agar dilution method the drug resistance of MRSA against 12
      antibiotics. RESULTS: 50.9% of the 210 Staphylococcus aureus strains were
      enterotoxin positive, and 97.1% of them carried hemolysin genes as all 51 strains
      of MRSA carried hemolsin genes. The 34 MRSA strains were divided into 10 STs,
      ranging in sequence ST239 (47.1%, 16/34), ST5 (17.6%, 6/34). Three MSSA strains
      belonged to ST188, ST1281 and ST7, respectively. Seventeen strains from the
      patients were divided into 6 STs, ranging in sequence ST239 (35.3%, 6/17) and ST5
      (29.4%, 5/17). Twenty strains from food sources were divided into 9 STs, ranging
      in sequence ST239 (45.0%, 9/20) and ST7 (15.0%, 3/20). STs of ST585, ST630 and
      ST239 were close in affinity, while the rest were distant in affinity. Except for
      vancomycin, all the strains were found with drug resistance to varying extent to
      the 10 antibiotics tested. CONCLUSION: Existence of Staphylococcus aureus
      hemotoxin was universal; ST239 was the main predominant MRSA in Maanshan region,
      with distant affinity among the STs.

PMID- 25975412
TI  - [Progress on the studies of association between clustered regularly interspaced
      short palindromic repeat and antibiotic resistance].

PMID- 25975413
TI  - What is the Acupoint? A preliminary review of Acupoints.
AB  - BACKGROUND: According to traditional Chinese medicine (TCM) theory, acupoints are
      specifically chosen sites of acupuncture manipulation, and also the basis for
      studying the mechanism of acupuncture. Stimulating different acupoints on the
      body surface could provide various therapeutic benefits. However, what is the
      acupoint? This question is not clear. REVIEW SUMMARY: We focuse on examining the
      function of acupoints from different perspectives, including the local and the
      systemic effects of stimulating acupoints. For example, acupoints may release
      certain substances or incur some changes, which could adjust the function of
      organs, maintain homeostasis. Furthermore, the therapeutic effects of verum
      acupoints versus sham acupoints were discussed. However, due to insufficience in
      evidence and in current methodologies, research into mechanisms of acupuncture is
      still incomplete. CONCLUSION: This review might explain, to some extent, what an
      acupoint is. Further research into the identity of acupoints is warranted, and
      multidisciplinary methods using novel technologies may yield significant advances
      over existing knowledge.

PMID- 25975414
TI  - Why is young maternal age at first childbirth a risk factor for persistent
      delinquency in their male offspring? Examining the role of family and parenting
      factors.
AB  - BACKGROUND: Children born to mothers who were younger than average at their first
      childbirth are at increased risk for future persistent delinquent behaviour, but
      explanations for this remain unclear. AIMS: Our aim was to identify possible
      family and parenting variables that may help explain this relationship. We
      hypothesised that parental stress, large number of children in the home, low
      socioeconomic status (including neighbourhood problems) and poor parenting would
      account for the link between early first motherhood and their offspring's
      delinquency. METHODS: Four hundred and sixty-two boys were selected from the
      Pittsburgh Youth Study, a longitudinal study of a random sample of school boys in
      Pittsburgh, initially assessed half-yearly and then annually from 7 to 19 years
      of age, using self-reporting and other reporting methods. Indirect effect models
      were used to test relationships between variables. RESULTS: Higher levels of
      parental stress, poorer parent-child communication and caring for a larger number
      of children all mediated the relationship between maternal youth and persistent
      delinquency by their boys, but only explained about 20% of it. DISCUSSION: At
      least partial explanations of the relationship between a mother's age at first
      childbirth and persistent delinquency in her male offspring suggest that future
      research should test whether early interventions with younger mothers to decrease
      their sense of stress in parenting and improve their capacity for communication
      with their child(ren) may help to prevent persistent delinquency in their boys.
      Programmes designed to help young women make more informed and planned decisions
      about their pregnancies should also be evaluated. Copyright (c) 2015 John Wiley &
      Sons, Ltd.

PMID- 25975415
TI  - The Many Faces of the A2b Adenosine Receptor in Cardiovascular and Metabolic
      Diseases.
AB  - Modulation of the low affinity adenosine receptor subtype, the A2b adenosine
      receptor (A2bAR), has gained interest as a therapeutic target in various
      pathologic areas associated with cardiovascular disease. The actions of the A2bAR
      are diverse and at times conflicting depending on cell and tissue type and the
      timing of activation or inhibition of the receptor. The A2bAR is a promising and
      exciting pharmacologic target, however, a thorough understanding of A2bAR action
      is necessary to reach the therapeutic potential of this receptor. This review
      will focus on the role of the A2bAR in various cardiovascular and metabolic
      pathologies in which the receptor is currently being studied. We will illustrate
      the complexities of A2bAR signaling and highlight areas of research with
      potential for therapeutic development.

PMID- 25975417
TI  - Adipose-Derived Mesenchymal Stem Cells (ADSCs) With the Potential to Ameliorate
      Platelet Recovery, Enhance Megakaryopoiesis, and Inhibit Apoptosis of Bone Marrow
      Cells in a Mouse Model of Radiation-Induced Thrombocytopenia.
AB  - Substantial damage to the bone marrow can be caused by exposure to radiation,
      which can then develop into severe thrombocytopenia. In this study, we
      investigated the in vivo impact of adipose-derived mesenchymal stem cells (ADSCs)
      on megakaryopoiesis and platelet recovery in irradiated mice. Radiation markedly
      reduced peripheral blood counts. Recovery of both platelets and WBCs was better
      in the ADSC-treated group compared with the saline group and the fibroblast group
      21 days after irradiation. A significant increase in the total CFU and MK-CFU
      after irradiation was observed in the ADSC group compared with the saline group
      and the fibroblast group. Further, the proportion of CD41(+) cells in the ADSC
      group was significantly higher than that in the saline group and the fibroblast
      group. ADSC treatment significantly improved the cellularity and decreased the
      apoptotic cells in the bone marrow while normal fibroblasts did not.
      Administration of ADSCs upregulated protein expression of phosphorylated Akt and
      Bcl-xL, whereas the expression of Bax, a protein related to apoptosis, was
      significantly lower in the ADSC group. In conclusion, this study suggests that
      ADSCs were capable of promoting platelet recovery, improving megakaryopoiesis,
      and inhibiting apoptosis of bone marrow cells in irradiated mice. The
      antiapoptotic effect of ADSCs is likely to be mediated via the PI3K/Akt pathway.
      These findings may provide a scientific basis for using ADSCs as a new therapy
      after irradiation. 

PMID- 25975416
TI  - Joint prognostic effect of obesity and chronic systemic inflammation in patients
      with metastatic colorectal cancer.
AB  - BACKGROUND: Obesity is strongly linked with chronic systemic inflammation, and
      each has been linked with disease progression and survival in patients with
      colorectal cancer (CRC). The authors investigated the joint prognostic effects of
      obesity and circulating cytokines in patients with metastatic CRC (mCRC), an
      understudied patient group. METHODS: In 242 chemotherapy-naive patients with
      mCRC, the authors measured a multiplex cytokine panel and abstracted
      clinicopathological features, height, and weight from medical records. Overall
      survival (OS) was calculated from the date of mCRC diagnosis until the date of
      death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox
      proportional hazards regression models. Cut points for cytokines were determined
      by restricted cubic spline regression. RESULTS: In multivariable models, elevated
      interleukin (IL)-8, IL-2 receptor alpha, and lactate dehydrogenase (LDH) emerged
      as significant predictors of poor OS (hazard ratio [HR] and 95% confidence
      interval [95% CI] for above vs below the (referent) knot point: 2.5 [95% CI, 1.7
      3.7], 1.9 [95% CI, 1.3-2.7], and 2.2 [95% CI, 1.6-3.1], respectively; all
      P<.001). Obesity (body mass index >=30 kg/m(2) ) was not found to be associated
      with OS, but appeared to modify the relationships observed with IL-8 and LDH,
      which were associated with a significant 4-fold and 5-fold risk of death,
      respectively, in obese patients compared with a 2-fold risk of death in nonobese
      patients (P for interaction of .06 and .04, respectively). Similar results
      emerged from joint effects analysis, in which obese patients with high IL-8 (or
      LDH) experienced the highest risk of death. CONCLUSIONS: Although obesity itself
      was not found to be independently associated with survival in patients with mCRC,
      the adverse prognostic significance of LDH and IL-8 was found to be enhanced in
      obese patients.

PMID- 25975418
TI  - Influence of bruxism and splint therapy on tongue pressure against teeth.
AB  - OBJECTIVES: This study estimated the maximum tongue pressure (MTP) against teeth
      in bruxers, and verified the effect of a stabilization splint. METHOD: Forty
      subjects (mean age: 26.57 years) were assigned to two groups (n520): bruxers and
      nonbruxers. Sleep bruxism was diagnosed by self-report, presence of tooth wear
      and tongue indentation, and by using a BiteStrip2 device. Maximum tongue pressure
      was measured by intraoral appliances containing pressure sensors. After baseline
      evaluation, bruxers received a stabilization splint and non-bruxers received a
      palatal splint, both for nocturnal use. Maximum tongue pressure was reassessed
      after 30 and 60 days. Data were submitted to repeated-measures ANOVA and Tukey
      test (Pv0.05). RESULTS: Bruxers showed an increased MTP against teeth (Pv0.05).
      Splint therapy decreased MTP for bruxers and non-bruxers. DISCUSSION: Bruxers
      present tongue indentations or ulcerations; however, there is no evidence on
      their MTP. Further research should focus on therapies to avoid tongue ulcerations
      in bruxers.

PMID- 25975419
TI  - Chemical protein synthesis.

PMID- 25975421
TI  - A sequence-function analysis of the silica precipitating silaffin R5 peptide.
AB  - The R5 peptide is derived from silaffin peptides naturally occurring in the
      diatom Cylindrotheca fusiformis and exhibits outstanding activity in silica
      precipitation. Because of its ability to cause silicification under mild
      conditions, several biotechnological applications based on R5-mediated biomimetic
      silica formation have already been reported. Yet a more detailed understanding of
      the R5 peptide and its intrinsic silica precipitation activity will help the
      rational design of R5 peptide variants as efficient agents for defined silica
      precipitation. The herein presented analysis of the relationship between the R5
      amino acid sequence and its activity in silica precipitation emphasizes the
      essential role of the lysine residues in mediating silica polycondensation.
      Furthermore, a tetra amino acid motif (RRIL) has to be present within the R5
      sequence, but in contrast to previous reports, we demonstrate that localization
      of the RRIL motif shows minor impact on silica precipitation activity but rather
      on morphology of the resulting silica material. The amino acid sequence of
      silaffin peptides is a well-balanced arrangement in terms of charges, functional
      groups and distances. The impact of this pattern of charges and functionalities
      was highlighted by the disturbed morphology of silica spheres resulting from R5
      variants with scrambled sequences. A detailed understanding of the highly evolved
      silaffin sequence(s) will contribute to unravel the intriguing process of silica
      biomineralization in diatoms.

PMID- 25975420
TI  - Safe and efficient Boc-SPPS for the synthesis of glycopeptide-alpha-thioesters.
AB  - Boc-solid phase peptide synthesis is useful for the preparation of peptide-alpha
      thioesters. However, this strategy usually employs hydrogen fluoride for the
      final deprotection step. These strongly acidic conditions cannot be applied for
      the synthesis of acid-labile glycopeptide-alpha-thioesters. The protocol
      presented here is a modified in situ neutralization Boc-solid phase peptide
      synthesis employing 10% sulfuric acid/dioxane conditions for intermediate Boc
      removal and TfOH for the final side-chain deprotection step. These conditions
      were found to be applicable for the synthesis of acid-labile glycopeptide-alpha
      thioesters. In this protocol, a glycopeptide is synthesized as alpha- thioester
      on a thiol linker, and the product glycopeptide-alpha-thioester is released from
      the resin by thiolysis after side-chain deprotection step with an acid cocktail
      containing TfOH instead of hydrogen fluoride.

PMID- 25975422
TI  - Congenital contractural arachnodactyly complicated with aortic dilatation and
      dissection: Case report and review of literature.
AB  - Congenital contractural arachnodactyly (CCA) is a connective tissue disease
      caused by mutations of the FBN2, which encodes fibrillin-2. CCA patients have a
      marfanoid habitus; however, aortic dilatation and/or dissection as observed in
      Marfan syndrome have been rarely documented. Here, we report on a Japanese
      familial case of CCA resulting from a FBN2 splicing mutation (IVS32+5g->a), which
      leads to exon 32 being skipped, and the patients developed aortic dilatation and
      type A dissection. Although CCA patients have been believed to have favorable
      prognoses, repetitive aortic imaging studies must be performed in some patients
      to detect possible aortic disease early, and genetic testing of FBN2 might be
      useful to identify such high-risk patients.

PMID- 25975423
TI  - Pharmacokinetic interaction between etravirine or rilpivirine and telaprevir in
      healthy volunteers: A randomized, two-way crossover trial.
AB  - Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      may require treatment with an HIV non-nucleoside reverse transcriptase inhibitor
      (NNRTI), for example, rilpivirine or etravirine, and an HCV direct-acting
      antiviral drug such as telaprevir. In a two-panel, two-way, crossover study,
      healthy volunteers were randomized to receive etravirine 200 mg twice daily +/-
      telaprevir 750 mg every 8 hours or rilpivirine 25 mg once daily +/- telaprevir
      750 mg every 8 hours. Pharmacokinetic assessments were conducted for each drug at
      steady-state when given alone and when coadministered; statistical analyses were
      least-square means with 90% confidence intervals. Telaprevir minimum plasma
      concentration (Cmin), maximum plasma concentration (Cmax), and area under the
      concentration-time curve (AUC) decreased 25%, 10%, and 16%, respectively, when
      coadministered with etravirine and 11%, 3%, and 5%, respectively, when
      coadministered with rilpivirine. Telaprevir did not affect etravirine
      pharmacokinetics, but increased rilpivirine Cmin, Cmax, and AUC by 93%, 49%, and
      78%, respectively. Both combinations were generally well tolerated. The small
      decrease in telaprevir exposure when coadministered with etravirine is unlikely
      to be clinically relevant. The interaction between telaprevir and rilpivirine is
      not likely to be clinically relevant under most circumstances. No dose
      adjustments are deemed necessary when they are coadministered. 

PMID- 25975424
TI  - The chemokine CXCL13 is elevated in the cerebrospinal fluid of patients with
      neurosyphilis.
AB  - BACKGROUND: The chemokine CXCL13 has been discussed as a diagnostic parameter
      with high specificity for Lyme neuroborreliosis (LNB) and as a marker of disease
      activity. Neurosyphilis and LNB share similar characteristics. We investigated
      retrospectively CXCL13 levels in the cerebrospinal fluid (CSF) of patients with
      neurosyphilis at initial diagnosis and during treatment. RESULTS: Five patients
      with neurosyphilis were identified retrospectively using an electronic database
      in a tertiary care hospital from 2005 to 2012. CXCL13 levels were measured using
      an ELISA. Five patients with definite LNB and 10 patients with multiple sclerosis
      (MS) served as controls. Median CXCL13 levels at baseline were 972 pg/mL for
      neurosyphilis patients, 8,000 pg/mL for LNB patients, and 7.8 pg/mL for MS
      patients. Patients with LNB and neurosyphilis showed significantly higher CXCL13
      levels in their CSF compared to MS patients (p < 0.05, p < 0.001, respectively).
      CXCL13 levels in the CSF declined during treatment. CONCLUSION: CXCL13 levels in
      the CSF of patients with neurosyphilis can be as high as in patients with LNB,
      exceeding the proposed threshold of 250 pg/mL for the diagnosis of LNB. Patients
      with encephalitic/myelitic syndromes appear to have especially high levels of
      CXCL13. Clinicians should be aware that high levels of CXCL13 are not found
      exclusively in LNB but also in other infectious diseases of the CNS.

PMID- 25975425
TI  - Metabolomics of cancer cell cultures to assess the effects of dietary
      phytochemicals.
AB  - Cancer is a multi-factorial disease and is a major cause of morbidity and
      mortality worldwide. Dietary phytochemicals have been used for the treatment of
      cancer throughout history due to their safety, low toxicity, and general
      availability. Several studies have been performed to elucidate the effects of
      dietary phytochemicals on cancer metabolism, and many molecular targets of
      phytochemicals have been discovered. In spite of remarkable progress, their
      effects on cancer metabolism have not yet been fully clarified. Recent
      developments in metabolomics allowed to probe much further the metabolism of
      cancer, highlighting altered metabolic pathways and offering a new powerful tool
      to investigate cancer disease. In this review, we discuss the main metabolic
      alterations of cancer cells and the potentiality of phytochemicals as promising
      modulators of cancer metabolism. We will focus on the application of nuclear
      magnetic resonance-based metabolomics on breast and hepatocellular cancer cell
      lines to evaluate the impact of curcumin and resveratrol on cancer metabolome
      with the aim to demonstrate the premise of this approach to provide useful
      information for a better understanding of impact of diet components on cancer
      disease.

PMID- 25975426
TI  - Probiotics and diseases of altered IgE regulation: A short review.
AB  - The use of probiotics has gained considerable popularity in the marketplace in
      the US and has been steadily increasing due to consumer interest in potential
      treatment of various diseases, which may be due to modulation of immune
      responses. The aim of this review is to present information from representative
      studies regarding some of the possible applications and clinical effects of
      probiotic use in diseases of altered immunoglobulin (IgE) regulation (allergic
      rhinitis (AR), asthma, atopic dermatitis (AD) and food sensitization). Reports in
      humans are sparse or controversial; there is currently little reliable scientific
      data that supports the theory that there exists a cause-effect relationship
      between taking probiotics and alleviation of allergic disease. Unfortunately,
      these findings are too variable to allow substantial conclusions as to the
      efficacy and effectiveness of probiotic use in these disease states. 

PMID- 25975427
TI  - IM-133N modulates cytokine secretion by RAW264.7 and THP-1 cells.
AB  - An indigenous herbal extract IM-133N containing extracts of Prosopis glandulosa
      Torr and Symplocos racemosa Roxb were evaluated for potential immunomodulatory
      effects using RAW264.7 and THP-1 cells. The incubation of the cells for 24 h with
      IM-133N over a dose range 0-125 ug/ml did not cause cytotoxicity that exceeded
      10%. The results indicated that non-cytotoxic doses of IM-133N effectively up
      regulated iNOS, TNFalpha, IL-6, IL-10, IL-8 and IFNgamma gene expression in both
      the RAW264.7 and THP-1 cells. The results also indicated IM-133N elicited dose
      related increases in nitric oxide (NO) and tumor necrosis factor (TNF)-alpha
      production by RAW264.7 or THP-1 cells. These results demonstrated that IM-133N
      could stimulate NO and induced pro-inflammatory cytokine expression by
      monocytes/macrophages. As clinical studies have shown IM-133N to be an effective
      immunomodulator without any adverse effects, the results of the present study
      provide further support for the potential use of this agent as an immunostimulant
      or as an immunotherapy adjuvant. 

PMID- 25975428
TI  - An association study between USP34 and polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactor disorder
      and genetic factors have been implicated in its pathogenesis. Our previous genome
      wide association study (GWAS) had identified allele frequencies in several single
      nucleotide polymorphisms (SNPs) in gene USP34 (Ubiquitin-Specific Protease 34)
      were significantly different between PCOS cases and controls. This study was
      aimed to replicate the previous results in another independent cohort. METHODS:
      One thousand two hundred eighteen PCOS cases and 1057 controls were recruited.
      Genotyping of two SNPs (rs17008097 and rs17008940) in USP34 gene were performed
      by TaqMan-MGB probe assay and genotype-phenotype analysis was conducted
      subsequently. RESULTS: The differences of allele or genotype frequencies were not
      significant statistically between PCOS and controls, even after age and BMI
      adjustment. For clinical and metabolic features (LH, T and HOMA-IR) analysis in
      PCOS cases, no statistical differences among three genotypes of rs17008097 and
      rs17008940 were found. However, rs17008940 was shown to be slightly associated
      with BMI in PCOS cases rather than in controls, even after age adjustment (TC vs
      CC P = 0.006, OR = 1.042, 95% CI 1.012-1.073; TT vs CC P = 0.037, OR = 1.050, 95%
      CI 1.003-1.100). CONCLUSIONS: USP34 gene polymorphisms (rs17008097 and
      rs17008940) may not be associated with PCOS in the Han Chinese women.

PMID- 25975430
TI  - Electronically excited states of PANH anions.
AB  - The singly deprotonated anion derivatives of nitrogenated polycyclic aromatic
      hydrocarbons (PANHs) are investigated for their electronically excited state
      properties. These include single deprotonation of the two unique arrangements of
      quinoline producing fourteen different isomers. This same procedure is also
      undertaken for single deprotonation of the three nitrogenation isomers of
      acridine and the three of pyrenidine. It is shown quantum chemically that the
      quinoline-class of PANH anion derivatives can only produce a candidate dipole
      bound excited state each, a state defined as the interaction of an extra electron
      with the dipole moment of the corresponding neutral. However, the acridine- and
      pyrenidine-classes possess valence excited states as well as the possible dipole
      bound excited states where the latter is only possible if the dipole moment is
      sufficiently large to retain the extra electron; the valence excitation is
      independent of the radical dipolar strength. As a result, the theoretical
      vertically computed electronic spectra of deprotonated PANH anion derivatives is
      fairly rich in the 1.5 eV to 2.5 eV range significantly opening the possibilities
      for these molecules to be applied to longer wavelength studies of visible and
      near-IR spectroscopy. Lastly, the study of these systems is also enhanced by the
      inclusion of informed orbital arrangements in a simply constructed basis set that
      is shown to be more complete and efficient than standard atom-centered functions.

PMID- 25975429
TI  - Prospective study of recovery from copperhead snake envenomation: an
      observational study.
AB  - BACKGROUND: Although much is known about signs, symptoms, and management in the
      acute phase of crotaline snake envenomation, little is known about signs,
      symptoms, function, and quality of life during the recovery phase. The purpose of
      this observational pilot investigation is to evaluate the utility of several
      clinical outcome instruments in the setting of copperhead snakebite, and to
      characterize the clinical course of recovery. METHODS: This is a multi-center
      prospective, open-label, observational study of patients envenomated by
      copperhead snakes. We administered the Disabilities of the Arm, Shoulder, and
      Hand (DASH), Lower Extremity Functional Scale (LEFS), Patient-Specific Functional
      Scale (PSFS), Work Productivity and Ability Impairment: Special Health Problem
      (WPAI: SHP), Patients' Global Impression of Change (PGIC), Patient's Global
      Assessment of Recovery (PGAR), and SF-36 instruments, obtained numeric pain
      rating scales, and measured grip strength, walking speed, and swelling prior to
      hospital discharge and 3, 7, 14, 21, and 28 days after envenomation. RESULTS: 20
      subjects were enrolled; none were lost to follow-up. Most (80%) had moderate
      severity swelling, and most (75%) received antivenom. Across the broad range of
      measures, abnormalities of pain, swelling, impairments of physical and role
      function, and quality of life persisted for 7-14 days in most subjects. Validated
      self-reported outcome measures, such as the DASH, LEFS, PSFS, PGIC, SF-36, and
      the daily activities impairment portion of the WPAI: SHP were more responsive
      than measurements of swelling or walking speed. Data quality issues limited the
      utility of the work impairment portion of the WPAI: SHP. Residual signs,
      symptoms, and impairment in some subjects lasted through the 28-day study period.
      The study design precluded any assessment of the effectiveness of antivenom.
      CONCLUSIONS: Signs, symptoms, impaired function, and decreased quality of life
      typically last 7 - 14 days after copperhead envenomation. Several tools appear
      responsive and useful in studying recovery from pit viper envenomation. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01651299.

PMID- 25975434
TI  - Addendum.

PMID- 25975431
TI  - New fluorinated fructose analogs as selective probes of the hexose transporter
      protein GLUT5.
AB  - Facilitated hexose transporters (GLUTs) mediate the transport of hexoses and
      other substrates across the membranes of numerous cell types, and while some are
      expressed ubiquitously (e.g., GLUT1), others are more tissue specific (e.g.,
      GLUT5). These properties have been exploited for the imaging of cancer cells by
      the use of hexose based probes, including fluorinated hexose derivatives for use
      with positron emission tomography (PET). However, design of new probes has been
      hampered by a limited understanding of how GLUT transporters interact with their
      substrates at the molecular level. Two fluorinated fructose surrogates designed
      for uptake by the GLUT5 transporter are described here: 3-deoxy-3-fluoro-D
      fructose (3-FDF) and 1-deoxy-1-fluoro-2,5-anhydromannitol (1-FDAM). Synthesis
      (both cold and radiolabeled) and in vitro analysis of their transport
      characteristics in two breast cancer cell lines (EMT-6 and MCF-7) expressing
      GLUT5 are detailed. Both analogues are readily taken up into both cancer cell
      lines, with uptake mediated primarily by GLUT5. They also have low IC50 values,
      indicating a high affinity for the transporter, suggesting that the uptake of
      these probes would be unaffected by endogenously circulating fructose. Selective
      uptake by GLUT5 was also demonstrated in Xenopus oocytes. Finally, these results
      are the first demonstration that a hexose existing predominantly in the pyranose
      ring structure (3-FDF) is transported by GLUT5, strongly suggesting that this
      transporter can handle both furanose and pyranose forms of fructose.

PMID- 25975435
TI  - Evidence of liquid crystal-assisted abiotic ligation of nucleic acids.
AB  - The emergence of early life must have been marked by the appearance in the
      prebiotic era of complex molecular structures and systems, motivating the
      investigation of conditions that could not only facilitate appropriate chemical
      synthesis, but also provide the mechanisms of molecular selection and structural
      templating necessary to pilot the complexification toward specific molecular
      patterns. We recently proposed and demonstrated that these functions could be
      afforded by the spontaneous ordering of ultrashort nucleic acids oligomers into
      Liquid Crystal (LC) phases. In such supramolecular assemblies, duplex-forming
      oligomers are held in average end-to-end contact to form chemically discontinuous
      but physically continuous double helices. Using blunt ended duplexes, we found
      that LC formation could both provide molecular selection mechanisms and boost
      inter-oligomer ligation. This paper provides an essential extension to this
      notion by investigating the catalytic effects of LC ordering in duplexes with
      mutually interacting overhangs. Specifically, we studied the influence of LC
      ordering of 5'-hydroxy-3'-phosphate partially self-complementary DNA 14mers with
      3'-CG sticky-ends, on the efficiency of non-enzymatic ligation reaction induced
      by water-soluble carbodiimide EDC as condensing agent. We investigated the
      ligation products in mixtures of DNA with poly-ethylene glycol (PEG) at three PEG
      concentrations at which the system phase separates creating DNA-rich droplets
      that organize into isotropic, nematic LC and columnar LC phases. We observe
      remarkable LC-enhanced chain lengthening, and we demonstrate that such
      lengthening effectively promotes and stabilizes LC domains, providing the kernel
      of a positive feedback cycle by which LC ordering promotes elongation, in turn
      stabilizing the LC ordering. 

PMID- 25975436
TI  - Management of the renovascular disease in children with Takayasu arteritis.
AB  - Takaysu arteritis (TA), together with fibromuscular dysplasia, is the most common
      cause for renovascular hypertension. The diagnosis of vasculitis is important to
      make as these children benefit from immunosuppressive treatment. In many cases,
      however, it is more difficult than commonly realised to differentiate between
      these two diagnoses. Imaging which allows the inflamed arterial wall to be
      outlined, such as magnetic resonance or positron emission tomography scans, can
      be very helpful in this context. Revascularisation, either with angioplasty or
      surgery, seems to be effective and safe, also in children with TA. Patients with
      inactive disease have a more successful outcome and experience fewer
      complications from the intervention than those with active on-going inflammation.

PMID- 25975438
TI  - Sediment Dynamics Within Buffer Zone and Sinkhole Splay Areas Under Extreme Soil
      Disturbance Conditions.
AB  - Sedimentation dynamics were assessed in sinkholes within training areas at Ft.
      Knox Military Installation, a karst landscape subjected to decades of tracked
      vehicle use and extreme soil disturbance. Sinkholes sampled were sediment-laden
      and behaved as intermittent ponds. Dendrogeomorphic analyses were conducted using
      willow trees (Salix spp.) located around the edge of 18 sinkholes to estimate
      historical sedimentation rates, and buried bottles were installed in 20 sinkholes
      at the center, outer edge, and at the midpoint between the center and edge to
      estimate annual sedimentation rates. Sedimentation data were coupled with
      vegetation characteristics of sinkhole buffers to determine relationships among
      these variables. The dendrogeomorphic method estimated an average accumulation
      rate of 1.27 cm year(-1) translating to a sediment loss rate of 46.1 metric ton
      year(-1) from the training areas. However, sediment export to sinkholes was
      estimated to be much greater (118.6 metric ton year(-1)) via the bottle method.
      These data suggest that the latter method provided a more accurate estimate since
      accumulation was greater in the center of sinkholes compared to the periphery
      where dendrogeomorphic data were collected. Vegetation data were not tightly
      correlated with sedimentation rates, suggesting that further research is needed
      to identify a viable proxy for direct measures of sediment accumulation in this
      extreme deposition environment. Mitigation activities for the sinkholes at Ft.
      Knox's tank training area, and other heavily disturbed karst environments where
      extreme sedimentation exists, should consider focusing on flow path and splay
      area management.

PMID- 25975437
TI  - Relationship of FGF23 to indexed left ventricular mass in children with non
      dialysis stages of chronic kidney disease.
AB  - BACKGROUND: The aim of this study was to evaluate the association of serum intact
      fibroblast growth factor 23 (FGF23) concentrations with indexed left ventricular
      mass in children with non-dialysis stages 3-5 of chronic kidney disease (CKD).
      METHODS: The study cohort comprised 83 children (51 boys; mean age 12.1 +/- 3.2
      years) with a mean estimated glomerular filtration rate (eGFR) of 32.3 +/- 14.6
      ml/min/1.73 m(2) who underwent clinic and ambulatory blood pressure measurement
      (ABPM), echocardiography and evaluation of biochemical markers of CKD-associated
      mineral bone disease. RESULTS: The mean left ventricular mass index (LVMI) was
      35.9 +/- 8.5 g/m(2.7) (+/- standard deviation), with 30 (36.1 %) children showing
      left ventricular hypertrophy (LVH), all eccentric, as defined using age-specific
      criteria. For all subjects, the mean FGF23 concentration was 142.2 +/- 204.4 ng/l
      and the normalised distribution following log transformation was 1.94 +/- 0.39.
      There was significant univariate correlation of LVMI with GFR, body mass index
      (BMI) z-score and calcium intake, but not with 24-h systolic ABPM z-score, log
      intact parathyroid hormone or log FGF23. On multivariate analysis following
      adjustment for confounders, only elemental calcium content (g/kg/day) estimated
      from prescribed calcium-based phosphate binder dose (beta = 154.9, p < 0.001) and
      BMI z-score (beta = 2.397, p = 0.003) maintained a significant positive
      relationship with LVMI (model r (2) = 0.225). CONCLUSIONS: We observed no
      significant relationship of FGF23 with LVMI. Larger studies in children are
      needed to clarify the roles of calcium-containing phosphate binders and FGF23
      with LV mass and their roles in the evolution of the development of adverse
      cardiovascular outcomes.

PMID- 25975439
TI  - Environmental Degradation in a Eutrophic Shallow Lake is not Simply Due to
      Abundance of Non-native Cyprinus carpio.
AB  - Non-native species are often major drivers of the deterioration of natural
      ecosystems. The common carp Cyprinus carpio are known to cause major changes in
      lentic systems, but may not be solely responsible for large scale changes in
      these ecosystems. We used data from extensive collection efforts to gain insight
      into the importance of carp as drivers of ecosystem change in Lake Patzcuaro,
      Mexico. We compared the structure (fish density, biomass, diversity, and
      evenness) of fish assemblages from six Lake Patzcuaro sites with different
      habitat characteristics. Intersite comparisons were carried out for both wet and
      dry seasons. We explored the relationships between non-carp species and carp; and
      studied multivariate interactions between fish abundance and habitat
      characteristics. From a biomass perspective, carp was dominant in only four of
      six sites. In terms of density, carp was not a dominant species in all sites.
      Further, carp density and biomass were not negatively related to native species
      density and biomass, even when carp density and biomass were positively
      correlated to water turbidity levels. Carp dominated fish assemblages in the
      shallowest sites with the highest water turbidity, plant detritus at the bottom,
      and floating macrophytes covering the lake surface. These results suggest that
      the effect of carp on fish assemblages may be highly dependent on habitat
      characteristics in Lake Patzcuaro. Watershed degradation, pollution, water level
      loss, and other sources of anthropogenic influence may be more important drivers
      of Lake Patzcuaro degradation than the abundance of carp. 

PMID- 25975440
TI  - Unraveling Landscape Complexity: Land Use/Land Cover Changes and Landscape
      Pattern Dynamics (1954-2008) in Contrasting Peri-Urban and Agro-Forest Regions of
      Northern Italy.
AB  - This study implements an exploratory data analysis of landscape metrics and a
      change detection analysis of land use and population density to assess landscape
      dynamics (1954-2008) in two physiographic zones (plain and hilly-mountain area)
      of Emilia Romagna, northern Italy. The two areas are characterized by different
      landscape types: a mixed urban-rural landscape dominated by arable land and peri
      urban settlements in the plain and a traditional agro-forest landscape in the
      hilly-mountain area with deciduous and conifer forests, scrublands, meadows, and
      crop mosaic. Urbanization and, to a lesser extent, agricultural intensification
      were identified as the processes underlying landscape change in the plain. Land
      abandonment determining natural forestation and re-forestation driven by man was
      identified as the process of change most representative of the hilly-mountain
      area. Trends in landscape metrics indicate a shift toward more fragmented and
      convoluted patterns in both areas. Number of patches, the interspersion and
      juxtaposition index, and the large patch index are the metrics discriminating the
      two areas in terms of landscape patterns in 1954. In 2008, mean patch size, edge
      density, interspersion and juxtaposition index, and mean Euclidean nearest
      neighbor distance were the metrics with the most different spatial patterns in
      the two areas. The exploratory data analysis of landscape metrics contributed to
      link changes over time in both landscape composition and configuration providing
      a comprehensive picture of landscape transformations in a wealthy European
      region. Evidence from this study are hoped to inform sustainable land management
      designed for homogeneous landscape units in similar socioeconomic contexts. 

PMID- 25975441
TI  - Propagation of pure fetal and maternal mesenchymal stromal cells from terminal
      chorionic villi of human term placenta.
AB  - Long term propagation of human fetal mesenchymal stromal cells (MSC) in vitro has
      proven elusive due to limited availability of fetal tissue sources and lack of
      appropriate methodologies. Here, we have demonstrated the presence of fetal and
      maternal cells within the tips of terminal chorionic villi (TCV) of normal human
      term placenta, and we have exploited inherent differences in the adhesive and
      migratory properties of maternal vs. fetal cells, to establish pure MSC cultures
      of both cell types. The origin and purity of each culture was confirmed by X-Y
      chromosome-specific fluorescence in situ hybridization (FISH) and short tandem
      repeat (STR) genotyping. This is the first demonstration of fetal and maternal
      cells in the TCV of human term placenta and also of deriving pure fetal MSC
      cultures from them. The concomitant availability of pure cultures of adult and
      fetal MSC from one tissue provides a good system to compare genetic and
      epigenetic differences between adult and fetal MSCs; and also to generate new
      models of cell based therapies in regenerative medicine. 

PMID- 25975442
TI  - Rhabdomyosarcoma in adults: new perspectives on therapy.
AB  - OPINION STATEMENT: Rhabdomyosarcoma (RMS) is well known as a pediatric disease.
      Most of the knowledge, like biology, genetics, and treatments of this disease,
      comes from studies done in that age group. The two subtypes of RMS, embryonic RMS
      and alveolar RMS, that affect mainly the pediatric population are well described
      in the literature and that has had an impact on the improvement in overall
      survival during the past 20 years. RMS in the adult population has a low
      incidence, therefor the study of RMS in this group is challenging. Pleomorphic
      RMS is the subtype that mainly affects adults and its biology and genetics are
      not yet completely understood and described. The risk factors for this tumor and
      the differences among adults and children is also poorly understood. The
      treatments for adults that have RMS are not standardized having an impact on the
      overall survival. Pleomorphic RMS has, compared to other adult sarcomas, poor
      overall survival. Adult patients with RMS have poor prognosis. The
      standardization of treatments for the adult population is necessary as maybe new
      treatments for this specific group. There are new treatment options that are
      being studied mostly in pediatrics and young adults. Immunotherapy is currently
      proposed as an important treatment possibility including different techniques
      like vaccination, antigen-mediated therapy, and immune checkpoints. Even if we
      have a better understanding of RMS, there are still unanswered questions. The
      improvements seen in the pediatric population are encouraging, but there is still
      the need to enhance better therapies for adults with RMS.

PMID- 25975443
TI  - Mantle Cell Lymphoma: First-line Therapy in Patients Not Eligible for Stem Cell
      Transplantation.
AB  - OPINION STATEMENT: Mantle cell lymphoma is a distinct subtype of non-Hodgkin's
      lymphoma, which has historically been associated with a poor prognosis. It is now
      recognized as a heterogeneous disease with variable biologic and clinical
      behavior. Treatment paradigms have evolved along two lines. Younger, fit mantle
      cell lymphoma (MCL) patients are generally treated with intensive strategies and
      older less fit patients with non-intensive strategies. Most of the published
      literature has focused on intensive strategies, which appear to result in more
      durable remissions, but with an unclear impact on overall survival. The
      literature is more sparse for the roughly 50% of patients who are not candidates
      for intensive strategies, and no "standard" approach has been established for
      this patient population. However, clues are emerging. Randomized clinical trials
      have (a) established that bendamustine-rituximab (BR) is more efficacious and
      less toxic than rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisone (R-CHOP); (b) established that bortezomib should replace vincristine
      if using an R-CHOP backbone; and (c) established that maintenance rituximab (MR)
      is beneficial after an R-CHOP induction. In our opinion, it is reasonable to
      extrapolate the data supporting MR after R-CHOP and apply MR after a BR
      induction. In our practice, we recommend BR followed by MR for 2 years to MCL
      patients not eligible for intensive therapy. An ongoing US intergroup trial is
      testing the addition of bortezomib to the BR backbone and the addition of
      lenalidomide to MR. This trial may establish a standard of care in the older MCL
      population. In addition, exciting options for relapsed MCL have emerged in the
      last few years, with the introduction of the Bruton tyrosine kinase (BTK)
      inhibitor ibrutinib and the development of the lenalidomide-rituximab
      combination. In this article, we will discuss the current available options for
      these older MCL patients and the evidence supporting those options.

PMID- 25975444
TI  - The role of infectious agents, antibiotics, and antiviral therapy in the
      treatment of extranodal marginal zone lymphoma and other low-grade lymphomas.
AB  - OPINION STATEMENT: There is strong evidence to corroborate the association with
      Helicobacter pylori (Hp) to gastric extranodal marginal zone lymphoma (ENMZL) and
      hepatitis C virus (HCV) to splenic/nodal marginal zone lymphoma. Koch's
      postulates generally hold for these two associations and eradication of the
      infectious agent is well supported. Hp eradication (HPE) is recommended as front
      line therapy for early stage gastric ENMZL regardless of Hp status. Complete
      response (CR) rate for Hp-negative patients is not as high as for Hp-positive
      patients; however, the benign nature of HPE and high rates of salvage allow this
      strategy to be safe while sparing some Hp-negative patients from systemic therapy
      or radiation. Similarly for HCV-seropositive patients, treatment with antivirals
      should be strongly considered as first-line for those who do not require
      immediate cytoreductive therapy or at some point even after completing
      chemoimmunotherapy. The controversy regarding the role for antibiotics is
      greatest for primary ocular adnexal lymphoma (POAL). Considering the low
      incidence of Chlamydia psittaci (Cp) infection with OAL and the challenges to
      reliably identifying Cp, we typically do not consider doxycycline in POAL
      treatment. Involved-field radiotherapy (IFRT) remains the treatment of choice for
      most with unilateral POAL. However, if reliable detection of Cp is available and
      Cp is identified, patients with unilateral low tumor stage POAL who do not
      require immediate radiotherapy could be considered for doxycycline as front-line
      treatment. Other infectious associations to indolent lymphomas have been made,
      including Borrelia borgdorferi (Bb) in cutaneous lymphoma and Campylobacter in
      immunoproliferative small intestinal disease (IPSID), but these associations are
      not as strong and primary treatment targeting the infectious agents is not
      recommended.

PMID- 25975445
TI  - Immunotherapeutic approaches to sarcoma.
AB  - OPINION STATEMENT: Current therapies in advanced sarcomas are primarily based on
      cytotoxic chemotherapy and have modest efficacy coupled with significant
      toxicity. Little progress has been made in the field since imatinib was approved
      for the treatment of gastrointestinal stromal tumor (GIST) in 2002 despite the
      recent FDA approval of the multi-tyrosine kinase inhibitor pazopanib. Novel
      therapies are clearly needed. Immunotherapy utilizing checkpoint inhibitors has
      yielded significant clinical benefit in multiple solid tumors manifesting as
      durable responses in melanoma, kidney, lung, and bladder cancers, as well as
      hematologic malignancies. Given the success in several "non-immunogenic" tumors
      and recent preclinical data, there is sufficient evidence to support the use of
      immunotherapy in sarcoma. Cytokine-based therapies have shown no benefit in the
      advanced setting. Two large randomized trials of muramyl tripeptide or of
      interferon maintenance in resected osteosarcoma patients did not provide
      unequivocal statistically significant benefit. More promising results have been
      reported in small studies evaluating vaccines and adoptive T cell therapy in
      specific subtypes of sarcoma such as synovial sarcoma, which widely expresses the
      immunogenic cancer testis antigen NY-ESO-1. Emerging approaches with chimeric
      antigen receptor (CAR)-engineered T cells are hypothesis-generating and thought
      provoking. However, the unprecedented clinical activity and excellent safety
      profile of checkpoint inhibitors targeting programmed death-1 receptor and its
      ligand (PD-1/PD-L1) have galvanized the field and generated much enthusiasm to
      harness the power of immunotherapy in pursuit of cures in patients with advanced
      sarcomas. An ongoing phase II study (SARC028) will hopefully usher an era of
      investigation of this exciting approach in sarcoma. However, it is unlikely that
      one agent will carry a universal cure and future approaches need to focus on
      patient selection as well as on identifying the optimal combination of checkpoint
      inhibitors with targeted therapy, chemotherapy, or radiation therapy.

PMID- 25975446
TI  - Preoperative therapy for extremity soft tissue sarcomas.
AB  - OPINION STATEMENT: High-risk soft tissue sarcomas (STS) are defined as large (>5
      cm), intermediate/high-grade tumors and can carry a >50 % risk of death from
      metastases. A regimen of preoperative chemoradiation immediately addresses issues
      of both local control and micrometastases and should be considered for patients
      with high-risk STS of the extremities. While acute wound healing complications
      are more likely to occur, these are most always manageable and reversible, as
      opposed to the long-term complications associated with higher radiation doses and
      larger fields required for post-operative therapy. Preoperative treatment also
      yields potential prognostic information from pathologic treatment response, and
      quantitative imaging methods hold promise to detect early treatment effect.
      Definitive evidence of survival benefit from neoadjuvant therapy has been
      elusive, but a large body of experience has accumulated at dedicated centers
      where this approach is utilized. Whenever possible, it is imperative that
      patients with high-risk STS be enrolled on well-designed clinical trials.
      Treatment planning and administration requires a coordinated multidisciplinary
      approach that should be undertaken in high-volume centers with expertise in the
      management of sarcomas.

PMID- 25975447
TI  - Evaluating information content of SNPs for sample-tagging in re-sequencing
      projects.
AB  - Sample-tagging is designed for identification of accidental sample mix-up, which
      is a major issue in re-sequencing studies. In this work, we develop a model to
      measure the information content of SNPs, so that we can optimize a panel of SNPs
      that approach the maximal information for discrimination. The analysis shows that
      as low as 60 optimized SNPs can differentiate the individuals in a population as
      large as the present world, and only 30 optimized SNPs are in practice sufficient
      in labeling up to 100 thousand individuals. In the simulated populations of 100
      thousand individuals, the average Hamming distances, generated by the optimized
      set of 30 SNPs are larger than 18, and the duality frequency, is lower than 1 in
      10 thousand. This strategy of sample discrimination is proved robust in large
      sample size and different datasets. The optimized sets of SNPs are designed for
      Whole Exome Sequencing, and a program is provided for SNP selection, allowing for
      customized SNP numbers and interested genes. The sample-tagging plan based on
      this framework will improve re-sequencing projects in terms of reliability and
      cost-effectiveness. 

PMID- 25975448
TI  - Inhibition of FHL1 inhibits cigarette smoke extract-induced proliferation in
      pulmonary arterial smooth muscle cells.
AB  - Cigarette smoke can induce pulmonary vascular remodeling, which involves
      pulmonary artery smooth muscle cell (PASMC) proliferation, resulting in pulmonary
      hypertension in chronic obstructive pulmonary disease. FHL1 is a member of the
      FHL subfamily, characterized by an N-terminal half LIM domain, followed by four
      complete LIM domains, and has been suggested to be critical in cell
      proliferation. However, the effects of FHL1 on cigarette smoke-induced PASMC
      proliferation and the precise molecular mechanism remain to be elucidated. The
      present study demonstrated that the protein expression of FHL1 correlated with
      cigarette smoke extract (CSE)-induced PASMC proliferation. Knockdown of the
      expression of FHL1 using siRNA significantly suppressed cell proliferation and
      inhibited the cell cycle transition between the G1 and S phase by regulating the
      cyclin-dependent kinase pathway at the basal level and following CSE stimulation.
      By contrast, overexpressing FHL1 using an adenovirus increased cell proliferation
      and promoted the cell cycle transition between the G1 and S phase. Furthermore,
      CSE significantly increased the protein expression of FHL1, however, exerted no
      effect on the mRNA expression levels. This alteration was due to the prolonged
      FHL1 half-life, leading to the antagonizing of protein degradation. Collectively,
      these data suggested that FHL1 may be involved in excessive cell proliferation
      and may represent a potential therapeutic target for pulmonary hypertension.

PMID- 25975449
TI  - Cancer literacy as a mediator for cancer screening behaviour in Korean adults.
AB  - This study investigates the cancer literacy level in Korean adults and examines
      whether cancer literacy plays a mediating role in the relationship between
      population characteristics and cancer screening behaviours. We collected data
      from 585 community-dwelling adults in Korea using self-administered surveys and
      face-to-face interviews from October to December in 2009. Guided by Andersen's
      behavioural model, we used a structural equation model to estimate the effect of
      cancer literacy as a mediator and found that cancer literacy mediated cancer
      screening behaviour. In the individual path analysis models, cancer literacy
      played a significant mediating role for the use of eastern medicine, fatalism,
      health status and the number of chronic diseases. When controlling for other
      relevant covariates, we found that in the optimal path model, cancer literacy
      played a mediating role in the relationship between the use of eastern medicine
      and self-rated health status as well as cancer screening behaviour. Thus,
      developing community-based cancer education programmes and training clinical
      practitioners in eastern medicine clinics about the importance of informing their
      patients about regular cancer screening may be an option to boost cancer literacy
      and screening behaviour in Korea.

PMID- 25975450
TI  - Practical calibration curve of small-type optically stimulated luminescence (OSL)
      dosimeter for evaluation of entrance skin dose in the diagnostic X-ray region.
AB  - For X-ray diagnosis, the proper management of the entrance skin dose (ESD) is
      important. Recently, a small-type optically stimulated luminescence dosimeter
      (nanoDot OSL dosimeter) was made commercially available by Landauer, and it is
      hoped that it will be used for ESD measurements in clinical settings. Our
      objectives in the present study were to propose a method for calibrating the ESD
      measured with the nanoDot OSL dosimeter and to evaluate its accuracy. The
      reference ESD is assumed to be based on an air kerma with consideration of a well
      known back scatter factor. We examined the characteristics of the nanoDot OSL
      dosimeter using two experimental conditions: a free air irradiation to derive the
      air kerma, and a phantom experiment to determine the ESD. For evaluation of the
      ability to measure the ESD, a calibration curve for the nanoDot OSL dosimeter was
      determined in which the air kerma and/or the ESD measured with an ionization
      chamber were used as references. As a result, we found that the calibration curve
      for the air kerma was determined with an accuracy of 5 %. Furthermore, the
      calibration curve was applied to the ESD estimation. The accuracy of the ESD
      obtained was estimated to be 15 %. The origin of these uncertainties was examined
      based on published papers and Monte-Carlo simulation. Most of the uncertainties
      were caused by the systematic uncertainty of the reading system and the
      differences in efficiency corresponding to different X-ray energies. 

PMID- 25975451
TI  - Crystallization seeds favour crystallization only during initial growth.
AB  - Crystallization represents the prime example of a disorder-order transition. In
      realistic situations, however, container walls and impurities are frequently
      present and hence crystallization is heterogeneously seeded. Rarely the seeds are
      perfectly compatible with the thermodynamically favoured crystal structure and
      thus induce elastic distortions, which impede further crystal growth. Here we use
      a colloidal model system, which not only allows us to quantitatively control the
      induced distortions but also to visualize and follow heterogeneous
      crystallization with single-particle resolution. We determine the sequence of
      intermediate structures by confocal microscopy and computer simulations, and
      develop a theoretical model that describes our findings. The crystallite first
      grows on the seed but then, on reaching a critical size, detaches from the seed.
      The detached and relaxed crystallite continues to grow, except close to the seed,
      which now prevents crystallization. Hence, crystallization seeds facilitate
      crystallization only during initial growth and then act as impurities. 

PMID- 25975453
TI  - Rheumatoid arthritis: biological drugs and risk of infection.

PMID- 25975454
TI  - Immediate lessons from the Nepal earthquake.

PMID- 25975452
TI  - Risk of serious infection in biological treatment of patients with rheumatoid
      arthritis: a systematic review and meta-analysis.
AB  - BACKGROUND: Serious infections are a major concern for patients considering
      treatments for rheumatoid arthritis. Evidence is inconsistent as to whether
      biological drugs are associated with an increased risk of serious infection
      compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did
      a systematic review and meta-analysis of serious infections in patients treated
      with biological drugs compared with those treated with traditional DMARDs.
      METHODS: We did a systematic literature search with Medline, Embase, Cochrane
      Central Register of Controlled Trials, and ClinicalTrials.gov from their
      inception to Feb 11, 2014. Search terms included "biologics", "rheumatoid
      arthritis" and their synonyms. Trials were eligible for inclusion if they
      included any of the approved biological drugs and reported serious infections. We
      assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian
      network meta-analysis of published trials using a binomial likelihood model to
      assess the risk of serious infections in patients with rheumatoid arthritis who
      were treated with biological drugs, compared with those treated with traditional
      DMARDs. The odds ratio (OR) of serious infection was the primary measure of
      treatment effect and calculated 95% credible intervals using Markov Chain Monte
      Carlo methods. FINDINGS: The systematic review identified 106 trials that
      reported serious infections and included patients with rheumatoid arthritis who
      received biological drugs. Compared with traditional DMARDs, standard-dose
      biological drugs (OR 1.31, 95% credible interval [CrI] 1.09-1.58) and high-dose
      biological drugs (1.90, 1.50-2.39) were associated with an increased risk of
      serious infections, although low-dose biological drugs (0.93, 0.65-1.33) were
      not. The risk was lower in patients who were methotrexate naive compared with
      traditional DMARD-experienced or anti-tumour necrosis factor biological drug
      experienced patients. The absolute increase in the number of serious infections
      per 1000 patients treated each year ranged from six for standard-dose biological
      drugs to 55 for combination biological therapy, compared with traditional DMARDs.
      INTERPRETATION: Standard-dose and high-dose biological drugs (with or without
      traditional DMARDs) are associated with an increase in serious infections in
      rheumatoid arthritis compared with traditional DMARDs, although low-dose
      biological drugs are not. Clinicians should discuss the balance between benefit
      and harm with the individual patient before starting biological treatment for
      rheumatoid arthritis. FUNDING: Rheumatology Division at the University of Alabama
      at Birmingham.

PMID- 25975455
TI  - Physical properties of cytoplasmic intermediate filaments.
AB  - Intermediate filaments (IFs) constitute a sophisticated filament system in the
      cytoplasm of eukaryotes. They form bundles and networks with adapted viscoelastic
      properties and are strongly interconnected with the other filament types,
      microfilaments and microtubules. IFs are cell type specific and apart from
      biochemical functions, they act as mechanical entities to provide stability and
      resilience to cells and tissues. We review the physical properties of these
      abundant structural proteins including both in vitro studies and cell
      experiments. IFs are hierarchical structures and their physical properties seem
      to a large part be encoded in the very specific architecture of the biopolymers.
      Thus, we begin our review by presenting the assembly mechanism, followed by the
      mechanical properties of individual filaments, network and structure formation
      due to electrostatic interactions, and eventually the mechanics of in vitro and
      cellular networks. This article is part of a Special Issue entitled:
      Mechanobiology. 

PMID- 25975456
TI  - Maternal serum copeptin, MR-proANP and procalcitonin levels at 11-13 weeks
      gestation in the prediction of preeclampsia.
AB  - PURPOSE: We investigated the potential value of maternal serum copeptin,
      midregional proatrial natriuretic peptide (MR-proANP) and Procalcitonin (PCT)
      levels at 11-13 weeks' gestation in the prediction of preeclampsia (PE) in a case
      control study. MATERIALS AND METHODS: Maternal serum concentration of copeptin,
      MR-proANP and PCT were measured at 11-13 weeks' gestation in cases of PE (n = 35)
      and controls (n = 100). The PE group was divided into early-onset PE (EO-PE) and
      late-onset PE (LO-PE). From the regression model, the value in each case and
      control was expressed as a multiple of the expected median (MoM). The Mann
      Whitney test was used to determine the significance of differences in the median
      MoM in each outcome group from that in the controls. RESULTS: In the PE group,
      compared to controls, maternal serum concentrations of copeptin, MR-proANP and
      PCT were not significantly different. CONCLUSION: The maternal serum copeptin, MR
      proANP and PCT levels are higher in EO-PE and LO-PE patients, but the difference
      is not significant. Thus, their levels in first trimester are not proven to be
      effective markers to screen for PE.

PMID- 25975458
TI  - Development of a Method to Observe Preschoolers' Packed Lunches in Early Care and
      Education Centers.
AB  - BACKGROUND: As early childhood education (ECE) centers become a more common
      setting for nutrition interventions, a variety of data collection methods are
      required, based on the center foodservice. ECE centers that require parents to
      send in meals and/or snacks from home present a unique challenge for accurate
      nutrition estimation and data collection. We present an observational methodology
      for recording the contents and temperature of preschool-aged children's
      lunchboxes and data to support a 2-day vs a 3-day collection period. METHODS:
      Lunchbox observers were trained in visual estimation of foods based on Child and
      Adult Care Food Program and MyPlate servings and household recommended measures.
      Trainees weighed and measured foods commonly found in preschool-aged children's
      lunchboxes and practiced recording accurate descriptions and food temperatures.
      Training included test assessments of whole-grain bread products, mixed dishes
      such as macaroni and cheese, and a variety of sandwich preparations. Validity of
      the estimation method was tested by comparing estimated to actual amounts for
      several distinct food types. Reliability was assessed by computing the intraclass
      correlation coefficient for each observer as well as an interrater reliability
      coefficient across observers. To compare 2- and 3-day observations, 2 of the 3
      days of observations were randomly selected for each child and analyzed as a
      separate dataset. Linear model estimated mean and standard error of whole grains,
      fruits and vegetables, and amounts of energy, carbohydrates, protein, total fat,
      saturated fat, dietary fiber, thiamin, riboflavin, niacin, vitamins A and C,
      calcium, iron, sodium, and dietary fiber per lunch were compared across the 2-
      and 3-day observation datasets. RESULTS: The mean estimated amounts across 11
      observers were statistically indistinguishable from the measured portion size for
      each of the 41 test foods, implying that the visual estimation measurement method
      was valid: intraobserver intraclass correlation coefficients ranged from 0.951
      (95% CI 0.91 to 0.97) to 1.0. Across observers, the interrater reliability
      correlation coefficient was estimated at 0.979 (95% CI 0.957 to 0.993).
      Comparison of servings of fruits, vegetables, and whole grains showed no
      significant differences for serving size or mean energy and nutrient content
      between 2- and 3-day lunch observations. CONCLUSIONS: The methodology is a valid
      and reliable option for use in research and practice that requires observing and
      assessing the contents and portion sizes of food items in preschool-aged
      children's lunchboxes in an ECE setting. The use of visual observation and
      estimation with Child and Adult Care Food Program and MyPlate serving sizes and
      household measures over 2 random days of data collection enables food handling to
      be minimized while obtaining an accurate record of the variety and quantities of
      foods that young children are exposed to at lunch time.

PMID- 25975457
TI  - Exploring Diet, Physical Activity, and Quality of Life in Females with Metastatic
      Breast Cancer: A Pilot Study to Support Future Intervention.
AB  - BACKGROUND: Historically, women with metastatic breast cancer are excluded from
      lifestyle interventions under the assumptions that diet and physical activity
      will have little impact on their disease trajectory. However, recent treatment
      advances have led to significant increases in survivorship that pose challenges
      to this assumption. OBJECTIVE: The objectives of this study were to measure
      dietary intake, physical functioning, and quality of life in a subset of women
      with metastatic breast cancer, and to inform future interventions in this growing
      population. DESIGN: Demographics, clinical characteristics, dietary intake,
      physical functioning, and quality of life were examined cross-sectionally using
      validated methodologies. PARTICIPANTS/SETTING: Twenty-five women with metastatic
      breast cancer were recruited during a 4-month period (June 2014 to September
      2014) from two university hospitals in the Midwest that serve an ethnically
      diverse patient population. Women completed questionnaires and 24-hour dietary
      recalls (1 weekday, 1 weekend). MAIN OUTCOME: Lifestyle habits were analyzed.
      STATISTICAL ANALYSES: Means (+/-standard deviations) and frequencies were tallied
      and t tests were conducted. RESULTS: On average, participants were 58.8 (+/-12.8)
      years of age, predominantly minority, had been living with metastatic breast
      cancer for a mean of 36.9 (+/-29.3) months, and exhibited significant nutrition
      impact symptomology (eg, pain, dry mouth, fatigue). Bone and lung were the most
      common sites of metastases. Compared to a larger, normative sample of women with
      metastatic breast cancer, study participants displayed similar physical (P=0.61)
      and functional well-being scores (P=0.76), but higher social (P=0.10) and
      emotional well-being scores (P<0.01). The analyses of lifestyle factors showed
      that the majority of women were overweight or obese (n=14), not routine
      exercisers (n=15), and had dietary patterns high in fat and low in fiber.
      CONCLUSIONS: This study supports that many women with metastatic breast cancer
      are in need of carefully tailored, evidence-based lifestyle strategies that
      address symptom burden, including weight management. The implications of diet and
      physical activity on quality of life in this population remain unexplored.

PMID- 25975459
TI  - Boston type 1 keratoprosthesis for failed keratoplasty.
AB  - The purpose of this study was to evaluate the outcomes of the Boston type 1
      keratoprosthesis (Kpro-1) in eyes with failed keratoplasty. A retrospective
      review was performed of every patient treated with a Kpro-1 at a tertiary eye
      care center between January 1, 2008 and July 1, 2013. Eyes with a failed
      keratoplasty originally performed for corneal edema, trauma, or keratoconus were
      included in the statistical analysis. The main outcome measures were visual
      outcome, prosthesis retention, and postoperative complications. Twenty-four eyes
      met the inclusion criteria, including 13 eyes with corneal edema, 8 eyes with
      trauma, and 3 eyes with keratoconus. After a mean follow-up period of 28.9 months
      (range 7-63 months), the median best corrected visual acuity (BCVA) was 20/125.
      The BCVA was >= 20/40 in 4 (16.7 %) eyes, >= 20/70 in 9 (37.5 %) eyes, and >=
      20/200 in 14 (58.3 %) eyes. Overall, the postoperative BCVA improved in 17 (70.9
      %) eyes, was unchanged in 3 (12.5 %) eyes, and was worse in 4 (16.7 %) eyes. The
      initial Kpro-1 was retained in 22 (91.7 %) eyes, and was successfully repeated in
      the other 2 eyes. One or more serious prosthesis- or sight-threatening
      complications occurred in 8 (33.3 %) eyes. These included 1 case of wound
      dehiscence leading to prosthesis extrusion, 1 case of fungal keratitis leading to
      prosthesis extrusion, 4 cases of endophthalmitis, and 5 retinal detachments. The
      Boston Kpro-1 is associated with an excellent prognosis for prosthesis retention
      and satisfactory visual improvement in eyes with previous failed keratoplasty.

PMID- 25975460
TI  - Conjunctival mucoepithelial hyperplasia of the elderly.
AB  - The ocular surface is exposed to many chronic inflammatory stimuli, and goblet
      cell hyperplasia of the conjunctiva occurs in many situations. We report two
      cases of epithelial goblet cell hyperplasia with nonspecific chronic inflammation
      which occurred on the internal canthus of elderly people. These cases shared the
      same clinicopathological features that mimicked neoplastic lesion
      macroscopically, but are composed of nonspecific inflammatory changes
      pathologically. Immunostaining of the tissue showed few IgG4+ plasma cells, and
      no neoplastic changes were observed. Both cases arose in elderly patients over
      the age of 80 years. Pathogenesis and clinical significance of the lesion is
      unclear, but it might be age related. Recognition of this diagnosis might help us
      avoid overdiagnosis of malignancy and to reach the correct diagnosis.

PMID- 25975461
TI  - Over-expression of AtGSTU19 provides tolerance to salt, drought and methyl
      viologen stresses in Arabidopsis.
AB  - The plant-specific tau class of glutathione S-transferases (GSTs) is often highly
      stress-inducible and expressed in a tissue-specific manner, thereby suggesting
      its important protective roles. Although activities associated with the binding
      and transport of reactive metabolites have been proposed, little is known about
      the regulatory functions of GSTs. Expression of AtGSTU19 is induced by several
      stimuli, but the function of this GST remains unknown. In this study, we
      demonstrated that transgenic over-expressing (OE) plants showed enhanced
      tolerance to different abiotic stresses and increased percentage of seed
      germination and cotyledon emergence. Transgenic plants exhibited an increased
      level of proline and activities of antioxidant enzymes, along with decreased
      malonyldialdehyde level under stress conditions. Real-time polymerase chain
      reaction (PCR) analyses revealed that the expression levels of several stress
      regulated genes were altered in AtGSTU19 OE plants. These results indicate that
      AtGSTU19 plays an important role in tolerance to salt/drought/methyl viologen
      stress in Arabidopsis.

PMID- 25975462
TI  - Pain-related comorbidities and medication absence as predictors of clinical
      remission in RA.

PMID- 25975463
TI  - XXII Congresso de Pneumologia Estoril, 8 a 10 de Dezembro de 2006.

PMID- 25975464
TI  - Editorial.

PMID- 25975465
TI  - [Not Available].

PMID- 25975466
TI  - Editorial.

PMID- 25975467
TI  - Interacting resident epicardium-derived fibroblasts and recruited bone marrow
      cells form myocardial infarction scar.
AB  - BACKGROUND: Although efforts continue to find new therapies to regenerate
      infarcted heart tissue, knowledge of the cellular and molecular mechanisms
      involved remains poor. OBJECTIVES: This study sought to identify the origin of
      cardiac fibroblasts (CFs) in the infarcted heart to better understand the
      pathophysiology of ventricular remodeling following myocardial infarction (MI).
      METHODS: Permanent genetic tracing of epicardium-derived cell (EPDC) and bone
      marrow-derived blood cell (BMC) lineages was established using Cre/LoxP
      technology. In vivo gene and protein expression studies, as well as in vitro cell
      culture assays, were developed to characterize EPDC and BMC interaction and
      properties. RESULTS: EPDCs, which colonize the cardiac interstitium during
      embryogenesis, massively differentiate into CFs after MI. This response is
      disease-specific, because angiotensin II-induced pressure overload does not
      trigger significant EPDC fibroblastic differentiation. The expansion of
      epicardial-derived CFs follows BMC infiltration into the infarct site; the number
      of EPDCs equals that of BMCs 1 week post-infarction. BMC-EPDC interaction leads
      to cell polarization, packing, massive collagen deposition, and scar formation.
      Moreover, epicardium-derived CFs display stromal properties with respect to BMCs,
      contributing to the sustained recruitment of circulating cells to the damaged
      zone and the cardiac persistence of hematopoietic progenitors/stem cells after
      MI. CONCLUSIONS: EPDCs, but not BMCs, are the main origin of CFs in the ischemic
      heart. Adult resident EPDC contribution to the CF compartment is time- and
      disease-dependent. Our findings are relevant to the understanding of post-MI
      ventricular remodeling and may contribute to the development of new therapies to
      treat this disease.

PMID- 25975468
TI  - Myocardial Infarct Scar: Hunting Down the Responsible Cells, But Then What?

PMID- 25975469
TI  - Trends in infective endocarditis incidence, microbiology, and valve replacement
      in the United States from 2000 to 2011.
AB  - BACKGROUND: In accordance with the 2007 American College of Cardiology and
      American Heart Association infective endocarditis (IE) guideline update,
      antibiotic prophylaxis is now being restricted to a smaller number of cardiac
      conditions with very high risk for adverse outcomes from IE. However, there is
      scant data on IE trends since this major practice change in the United States.
      OBJECTIVES: The aim of this study was to compare temporal trends in IE incidence,
      microbiology, and outcomes before and after the change in the 2007 IE prophylaxis
      guideline in the United States. METHODS: The NIS (Nationwide Inpatient Sample)
      database was used to investigate IE hospitalization rates in the United States
      from 2000 through 2011. The mean annual rates of IE before and after the 2007
      guideline change were compared using segmented regression analysis. RESULTS:
      There were 457,052 IE-related hospitalizations in the United States from 2000 to
      2011, with a steady increase in incidence (p < 0.001). The trend in IE
      hospitalization rates from 2000 to 2007 and from 2008 to 2011 was not
      significantly different (p = 0.74). The increases in the number of Staphylococcus
      IE cases per million population during the study periods 2000 to 2007 and 2008 to
      2011 were similar (p = 0.13), but Streptococcus IE hospitalization rates were
      significantly higher after the release of new guidelines (p = 0.002). Finally,
      valve replacement rates for IE steadily increased from 2000 to 2007 (p = 0.03)
      but showed a plateau from 2007 to 2011. Overall, there was no significant
      difference in the rates of valve replacement for IE before and after the release
      of new guideline (p = 0.23). CONCLUSIONS: These results show that IE incidence
      has increased in the United States over the past decade. With regard to the
      microbiology of IE, there has been a significant rise in the incidence of
      Streptococcus IE since the 2007 guideline revisions. However, the rates of
      hospitalization and valve surgery for IE have not increased since the change in
      IE prophylaxis guideline in 2007.

PMID- 25975471
TI  - The gap in cardiac rehabilitation referral: a system-based problem with system
      based solutions.

PMID- 25975470
TI  - Gaps in referral to cardiac rehabilitation of patients undergoing percutaneous
      coronary intervention in the United States.
AB  - BACKGROUND: Rates of referral to cardiac rehabilitation after percutaneous
      coronary intervention (PCI) have been historically low despite the evidence that
      rehabilitation is associated with lower mortality in PCI patients. OBJECTIVES:
      This study sought to determine the prevalence of and factors associated with
      referral to cardiac rehabilitation in a national PCI cohort, and to assess the
      association between insurance status and referral patterns. METHODS: Consecutive
      patients who underwent PCI and survived to hospital discharge in the National
      Cardiovascular Data Registry between July 1, 2009 and March 31, 2012 were
      analyzed. Cardiac rehabilitation referral rates, and patient and institutional
      factors associated with referral were evaluated for the total study population
      and for a subset of Medicare patients presenting with acute myocardial
      infarction. RESULTS: Patients who underwent PCI (n = 1,432,399) at 1,310
      participating hospitals were assessed. Cardiac rehabilitation referral rates were
      59.2% and 66.0% for the overall population and the AMI/Medicare subgroup,
      respectively. In multivariable analyses, presentation with ST-segment elevation
      myocardial infarction (odds ratio 2.99; 95% confidence interval: 2.92 to 3.06)
      and non-ST-segment elevation myocardial infarction (odds ratio: 1.99; 95%
      confidence interval: 1.94 to 2.03) were associated with increased odds of
      referral to cardiac rehabilitation. Models adjusted for insurance status showed
      significant site-specific variability in referral rates, with more than one
      quarter of all hospitals referring <20% of patients. CONCLUSIONS: Approximately
      60% of patients undergoing PCI in the United States are referred for cardiac
      rehabilitation. Site-specific variation in referral rates is significant and is
      unexplained by insurance coverage. These findings highlight the potential need
      for hospital-level interventions to improve cardiac rehabilitation referral rates
      after PCI.

PMID- 25975473
TI  - Improving fitness to achieve health: shifting the focus from theory to practice.

PMID- 25975472
TI  - The effect of cardiorespiratory fitness on age-related lipids and lipoproteins.
AB  - BACKGROUND: Evidence on the effect of cardiorespiratory fitness (CRF) on age
      related longitudinal changes of lipids and lipoproteins is scarce. OBJECTIVES:
      This study sought to assess the longitudinal aging trajectory of lipids and
      lipoproteins for the life course in adults and to determine whether CRF modifies
      the age-associated trajectory of lipids and lipoproteins. METHODS: Data came from
      11,418 men, 20 to 90 years of age, without known high cholesterol, high
      triglycerides, cardiovascular disease, and cancer at baseline and during follow
      up from the Aerobics Center Longitudinal Study. There were 43,821 observations
      spanning 2 to 25 health examinations (mean 3.5 examinations) between 1970 and
      2006. CRF was quantified by a maximal treadmill exercise test. Marginal models
      using generalized estimating equations were applied. RESULTS: Total cholesterol
      (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high
      density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped
      quadratic trajectories with aging: gradual increases were noted until age mid-40s
      to early 50s, with subsequent declines (all p < 0.0001). Compared with men with
      higher CRF, those with lower CRF developed abnormal values earlier in life: TC
      (>=200 mg/dl), LDL-C (>=130 mg/dl), non-HDL-C (>=160 mg/dl), and
      triglycerides/HDL-C ratio (>=3.0). Notably, abnormal values for TC and LDL-C in
      men with low CRF were observed around 15 years earlier than in those with high
      CRF. After adjusting for time-varying covariates, a significant interaction was
      found between age and CRF in each trajectory, indicating that CRF was more
      strongly associated with the aging trajectories of lipids and lipoproteins in
      young to middle-age men than in older men. CONCLUSIONS: Our investigation reveals
      a differential trajectory of lipids and lipoproteins with aging according to CRF
      in healthy men and suggests that promoting increased CRF levels may help delay
      the development of dyslipidemia.

PMID- 25975475
TI  - Between Death and Hope After Out-of-Hospital Cardiac Arrest: Should We Rely on
      Biomarkers?

PMID- 25975474
TI  - Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome
      After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33
      degrees C and 36 degrees C.
AB  - BACKGROUND: Neuron-specific enolase (NSE) is a widely-used biomarker for
      prognostication of neurological outcome after cardiac arrest, but the relevance
      of recommended cutoff values has been questioned due to the lack of a
      standardized methodology and uncertainties over the influence of temperature
      management. OBJECTIVES: This study investigated the role of NSE as a prognostic
      marker of outcome after out-of-hospital cardiac arrest (OHCA) in a contemporary
      setting. METHODS: A total of 686 patients hospitalized after OHCA were randomized
      to targeted temperature management at either 33 degrees C or 36 degrees C. NSE
      levels were assessed in blood samples obtained 24, 48, and 72 h after return of
      spontaneous circulation. The primary outcome was neurological outcome at 6 months
      using the cerebral performance category score. RESULTS: NSE was a robust
      predictor of neurological outcome in a baseline variable-adjusted model, and
      target temperature did not significantly affect NSE values. Median NSE values
      were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54
      ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p < 0.001).
      At 48 and 72 h, NSE predicted neurological outcome with areas under the receiver
      operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false
      positive rates <=5% and tight 95% confidence intervals were able to reliably
      predict outcome. CONCLUSIONS: High, serial NSE values are strong predictors of
      poor outcome after OHCA. Targeted temperature management at 33 degrees C or 36
      degrees C does not significantly affect NSE levels. (Target Temperature
      Management After Cardiac Arrest [TTM]; NCT01020916).

PMID- 25975476
TI  - 2015 ACC Health Policy Statement on Cardiovascular Team-Based Care and the Role
      of Advanced Practice Providers.
AB  - The mission of the American College of Cardiology is "to transform cardiovascular
      care and improve heart health." Cardiovascular team-based care is a paradigm for
      practice that can transform care, improve heart health, and help meet the demands
      of the future. One strategic goal of the College is to help members successfully
      transition their clinical practices to the future, with all its complexity,
      challenges, and opportunities. The ACC's strategic plan is aligned with the
      triple aim of improved care, improved population health, and lower costs per
      capita. The traditional understanding of quality, access, and cost is that you
      cannot improve one component without diminishing the others. With cardiovascular
      team-based care, it is possible to achieve the triple aim of improving quality,
      access, and cost simultaneously to also improve cardiovascular health. Striving
      to serve the best interests of patients is the true north of our guiding
      principles. Cardiovascular team-based care is a model that can improve care
      coordination and communication and allow each team member to focus more on the
      quality of care. In addition, the cardiovascular team-based care model increases
      access to cardiovascular care and allows expansion of services to populations and
      geographic areas that are currently underserved. This document will increase
      awareness of the important components of cardiovascular team-based care and
      create an opportunity for more discussion about the most creative and effective
      means of implementing it. We hope that this document will stimulate further
      discussions and activities within the ACC and beyond about team-based care. We
      have identified areas that need improvement, specifically in APP education and
      state regulation. The document encourages the exploration of collaborative care
      models that should enable team members to optimize their education, training,
      experience, and talent. Improved team leadership, coordination, collaboration,
      engagement, and efficiency will enable the delivery of higher-value care to the
      betterment of our patients and society.

PMID- 25975477
TI  - The changing face of team care, and a challenge for the future.

PMID- 25975478
TI  - The American College of Cardiology's Board of Governors: Overcoming Obstacles to
      Providing Care.

PMID- 25975479
TI  - Organizing a career in global cardiovascular health.

PMID- 25975480
TI  - Prevalence and Clinical Significance of Life-Threatening Arrhythmias in Takotsubo
      Cardiomyopathy.

PMID- 25975481
TI  - Body fat distribution and incident cardiovascular disease in obese adults.

PMID- 25975482
TI  - Copper, coronary heart disease, and dehydroepiandrosterone.

PMID- 25975483
TI  - Recognizing Sex Similarities in Cardiovascular Disease Research.

PMID- 25975484
TI  - Aspirin Treatment and Outcomes After Percutaneous Coronary Intervention: Results
      of the ISAR-ASPI Registry.

PMID- 25975485
TI  - Reply: Recognizing Sex Similarities in Cardiovascular Disease Research Copper,
      Coronary Heart Disease, and Dehydroepiandrosterone.

PMID- 25975486
TI  - Reply: Aspirin Treatment and Outcomes After Percutaneous Coronary Intervention:
      Results of the ISAR-ASPI Registry.

PMID- 25975487
TI  - Does size matter? In search of a physiological definition of myocardial atrophy.

PMID- 25975488
TI  - Reply: does size matter? In search of a physiological definition of myocardial
      atrophy.

PMID- 25975489
TI  - Salvianolic acid B attenuates lung inflammation induced by cigarette smoke in
      mice.
AB  - Salvianolic acid B (Sal B), a bioactive compound isolated from the Chinese herb
      Radix Salviae Miltiorrhizae, has been reported to exhibit anti-inflammatory and
      anti-oxidantive effects. The aim of this study was to investigate the protective
      effects of Sal B on cigarette smoke (CS)-induced acute lung inflammation. Sal B
      was given intraperitoneally (i.p.) to mice 1h before CS exposure daily for four
      consecutive days. Bronchoalveolar lavage fluid (BALF) was collected to assess the
      levels of inflammatory cytokines and cell counts. Lung tissues were used to
      analysis pathological changes, total glutathione (GSH), nuclear factor erythroid
      2 related factor 2 (Nrf-2), and nuclear factor-kappa B (NF-kappaB) expression.
      The results showed that Sal B inhibited CS-induced lung pathological changes, the
      infiltration of inflammatory cells, tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and monocyte chemoattractant
      protein 1 (MCP-1) productions. Sal B also up-regulated CS-induced total
      glutathione (GSH) production. Furthermore, Sal B was found to up-regulate Nrf-2,
      hemeoxygenase1 (HO1) expression and suppress CS-induced NF-kappaB activation. In
      conclusion, the current study demonstrated that Sal B exhibited a protective
      effect on CS-induced lung injury and the possible mechanism was involved in
      activating Nrf-2 and inhibiting NF-kappaB activation. 

PMID- 25975490
TI  - Host systemic inflammatory response influences outcome in pancreatic cancer.
AB  - This review of the influence of host systemic inflammatory response(SIR) on the
      outcome of pancreatic ductal adenocarcinoma (PDAC)was the kernel of the 2014
      George E Palade Memorial Prize Lecture at the Combined IAP-EPC Meeting held June
      25-8 in Southampton,UK. The ability of the modified Glasgow Prognostic
      Score(mGPS) to stratify cancer outcomes has been demonstrated in >50 studies
      including >25000 patients from many countries. Other markers of SIR such as
      Prognostic Index and neutrophil/lymphocyte ratio(NLR) may also be used
      emphasising the non homogeneity of the PDAC patients. The mGPS score 0 is
      associated with better outcome,while scores of 1 & 2 are linked to poor
      performance status, greater weight loss, comorbidity and earlier death. Two
      papers show in resectable PDAC that longer life (27-37 months) occurs with mGPS
      0, and < 18 months for mGPS 1 and 2, such that alternative therapy employing RFA
      may well be better than resection in those patients. In the greater number of
      PDAC patients unsuitable for resection the JAK-STAT inhibitor, ruxolitinib, has
      been found only to favourably modify PDAC in those with mGPS 1 or 2. Likewise the
      possible benefits of older anti inflammatory agents may be confined to these
      patients. An urgent reappraisal of the prognostic and therapeutic implications is
      now required in PDAC. Local inflammatory responses(LIR) are beneficial in PDAC
      and other cancers. Four grade stratification systems using Klintrup histology, T
      cell subtype analysis and Galon immune scores are accurate prognosticators. 

PMID- 25975493
TI  - Stereotactic radiosurgery for merkel cell carcinoma brain metastases.
AB  - In this report we propose a novel approach to treat merkel cell carcinoma (MCC)
      brain metastases and present a review of the literature in an attempt to
      establish a treatment algorithm and provide prognosis. MCC is a rare
      neuroendocrine malignancy affecting the aging population. This malignancy has a
      very aggressive behavior with frequent metastases. We report a 61-year-old man
      with a prior history of MCC who presented with diplopia. Brain MRI revealed a
      single right thalamic lesion consistent with metastasis. In the two weeks
      following GammaKnife stereotactic radiosurgery (Elekta, Stockholm, Sweden) the
      diplopia improved. A brain MRI demonstrated shrinkage of the tumor. From our
      literature search we found only six other patients with MCC brain metastases. The
      majority of these patients were treated with whole brain radiation in conjunction
      with chemotherapy. We propose that stereotactic radiosurgery can be used as a
      first line therapy for patients with MCC metastatic brain disease. 

PMID- 25975492
TI  - Quantitative assessment of the association between GAK rs1564282 C/T polymorphism
      and the risk of Parkinson's disease.
AB  - The aim of this meta-analysis was to evaluate the association between cyclin G
      associated kinase (GAK) rs1564282 C/T polymorphism and Parkinson's disease (PD)
      susceptibility. GAK modifies alpha-synuclein expression levels and affects
      susceptibility to PD. Genetic variation in GAK may influence the risk of
      occurrence and progression of PD. Many studies have evaluated the association
      between GAK rs1564282 C/T polymorphism and the risk of PD. However, published
      data are still controversial. Nine case-control studies with a total of 8159 PD
      patients and 12,747 controls were included in the meta-analysis. The summary odds
      ratio with 95% confidence interval was calculated to estimate this association.
      Both the minor allele frequencies and the genotype distributions of rs1564282
      within GAK were different between the two groups when all studies were pooled.
      Subgroup analysis by ethnicity showed GAK rs1564282 C/T polymorphism was
      significantly associated with increased risk in both Asian and Caucasian
      populations. This meta-analysis suggests that GAK rs1564282 C/T polymorphism is
      associated with increased susceptibility to PD. 

PMID- 25975495
TI  - A brief review on biomarkers and proteomic approach for malaria research.
AB  - Malaria remains as one of the significant health threat to people living in
      countries throughout tropical and subtropical zones. Proteomic studies of
      Plasmodium, the protozoan causing malaria, is essential for understanding its
      cellular structure, growth stage-specific expression of protein metabolites and
      complex interaction with host. In-depth knowledge of the pathogen is required for
      identification of novel biomarkers that can be utilized to develop diagnostic
      tests and therapeutic antimalarial drugs. The alarming rise in drug-resistant
      strains of Plasmodium has created an urgent need to identify new targets for drug
      development that can act by obstructing life cycle of this parasite. In the
      present review, we briefly discuss on role of various biomarkers including
      Plasmodium-associated aldolase, histidine-rich proteins and lactate dehydrogenase
      for diagnosis of malaria. Here we also summarize the present and future prospects
      of currently used techniques in proteomic approaches such as two dimensional gel
      electrophoresis and matrix-assisted laser desorption/ionization-time of flight
      (MALDI-TOF) for diagnosis and potential identification of novel proteins for
      malaria research. 

PMID- 25975491
TI  - Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic
      worm product prevents experimental arthritis and inhibits IL-1beta production via
      NRF2-mediated counter-regulation of the inflammasome.
AB  - Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many
      patients are refractory to existing conventional and biologic therapies, and
      hence successful development of novel treatments remains a critical requirement.
      Towards this, we now describe a synthetic drug-like small molecule analogue, SMA
      12b, of an immunomodulatory parasitic worm product, ES-62, which acts both
      prophylactically and therapeutically against collagen-induced arthritis (CIA) in
      mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a
      number of inflammatory response genes, particularly those associated with the
      inflammasome in mouse bone marrow-derived macrophages and indeed IL-1beta was the
      most down-regulated gene. Consistent with this, IL-1beta was significantly
      reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also
      increased the expression of a number of genes associated with anti-oxidant
      responses that are controlled by the transcription factor NRF2 and critically,
      was unable to inhibit expression of IL-1beta by macrophages derived from the bone
      marrow of NRF2(-/-) mice. Collectively, these data suggest that SMA-12b could
      provide the basis of an entirely novel approach to fulfilling the urgent need for
      new treatments for RA. 

PMID- 25975494
TI  - Vitamin A intake and serum retinol levels in children and adolescents with cystic
      fibrosis.
AB  - BACKGROUND: Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin
      A supplementation according to CF-specific recommendations to prevent
      deficiencies. Whether current recommendations are optimal for preventing both
      deficiency and toxicity is a subject of debate. We assessed the longitudinal
      relation between serum retinol levels and appropriate variables. METHODS: We
      studied vitamin A intake, and the long-term effects of vitamin A intake,
      coefficient of fat absorption (CFA) and immunoglobulin G (IgG) on serum retinol
      levels in 221 paediatrics CF patients during a seven-year follow up period.
      RESULTS: Total vitamin A intake, derived from 862 dietary assessments, exceeded
      the tolerable upper intake level in 30% of the assessments, mainly up to age six.
      Although CF patients failed to meet the CF-specific recommendations, serum
      retinol deficiency was found in only 17/862 (2%) of the measurements.
      Longitudinally, we observed no association to serum retinol levels for total
      vitamin A intake, CFA, gender or age but serum retinol levels were associated
      with serum IgG levels. Each g/L increase in serum IgG level would result in a
      2.49% (95% CI -3.60 to -1.36%) reduction in serum retinol levels. CONCLUSION: In
      this large sample of children and adolescents with CF, serum retinol deficiency
      was rare despite lower than the CF-specific recommendations. However, the TUL was
      commonly exceeded. A reduction in CF-specific vitamin A supplementation
      recommendations should therefore be considered. Moreover, serum retinol levels
      were not associated with vitamin A intake, CFA, gender or age, although a
      decreased serum retinol was associated with an increased serum IgG.

PMID- 25975496
TI  - Trigonelline protects the cardiocyte from hydrogen peroxide induced apoptosis in
      H9c2 cells.
AB  - OBJECTIVE: To elucidate the key parameters associated with hydrogen peroxide
      induced oxidative stress and investigates the mechanism of trigonelline (TG) for
      reducing the H2O2 induced toxicity in H9c2 cells. METHODS: Cytotoxicity and
      antioxidant activity of TG was assessed by EZ-CYTOX kit. RNA extraction and cDNA
      synthesized according to the kit manufacture protocol. Apoptosis was measured by
      the Flowcytometry, general PCR and qPCR. RESULTS: It was found that the TG
      significantly rescued the morphology of the H9c2 cells. Treatment of cells with
      TG attenuated H2O2 induced cell deaths and improved the antioxidant activity. In
      addition, TG regulated the apoptotic gene caspase-3, caspase-9 and anti-apoptotic
      gene Bcl-2, Bcl-XL during H2O2 induced oxidative stress in H9c2 cells. These
      results were comparable with quercetin treatment. For evident, flow cytometer
      results also confirmed the TG significantly reduced the H2O2 induced necrosis and
      apoptosis in H9c2 cells. However, further increment of TG concentration against
      H2O2 could induce the necrosis and apoptosis along with H2O2. CONCLUSIONS: It is
      suggested that less than 125 MU M of TG could protect the cells from H2O2 induced
      cell damage by down regulating the caspases and up regulating the Bcl-2 and Bcl
      XL expression. Therefore, we suggest the trigonelline could be useful for
      treatment of oxidative stress mediated cardiovascular diseases in future.

PMID- 25975497
TI  - In vitro cholinesterase inhibitory and antioxidant effect of selected coniferous
      tree species.
AB  - OBJECTIVE: To explore cholinesterase inhibitory and antioxidant effect of six
      coniferous trees (Abies bornmulleriana, Picea pungens, Juniperus communis, Cedrus
      libani, Taxus baccata, and Cupressus sempervirens var. horizantalis). METHODS:
      Acetone (Ace), ethyl acetate (EtOAc), and ethanol (EtOH) extracts prepared from
      the needles and shoots of the six coniferous trees were screened for their
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity
      at 100 MUg/mL. Antioxidant activity of the extracts was tested using 2,2-diphenyl
      1-picrylhydrazyl (DPPH) and N,N-dimethyl-p-phenylendiamine (DMPD) radical
      scavenging, metal-chelation capacity, ferric-(FRAP) and phosphomolibdenum
      reducing antioxidant power (PRAP) assays. All of the assays were performed in
      ELISA microplate reader. Total phenol and flavonoid amounts in the extracts were
      determined spectrophotometrically. RESULTS: Among thirty-six extracts in total,
      the shoot-Ace extract of Cupressus sempervirens var. horizantalis exerted the
      highest inhibition against AChE [(54.84+/-2.51)%], while the needle-Ace extract
      of Cedrus libani was the most effective in inhibiting BChE [(67.54+/-0.30)%]. The
      highest DPPH radical scavenging effect, FRAP and PRAP was observed in the shoot
      Ace and EtOAc extracts from Taxus baccata, whereas all the extracts showed a
      variable degree of scavenging effect against DPMD radical. The shoot-EtOAc
      extract of Cedrus libani had the highest metal-chelation capacity [(58.04+/
      0.70)%]. The shoot extracts of Taxus baccata were determined to have the richest
      total phenol content, which may contribute to its marked antioxidant activity.
      CONCLUSIONS: The conifer species screened in this study may contain
      cholinesterase-inhibiting and antioxidant properties, which might be useful
      against Alzheimer's disease.

PMID- 25975498
TI  - Monascus pilosus-fermented black soybean inhibits lipid accumulation in
      adipocytes and in high-fat diet-induced obese mice.
AB  - OBJECTIVE: To explore the anti-obesity effects and the mechanism of action of
      Monascus pilosus(M. pilosus)-fermented black soybean (MFBS) extracts (MFBSE) and
      MFBS powders (MFBSP) in adipocytes and high-fat diet (HFD)-induced obese mice,
      respectively. METHODS: Black soybean was fermented with M. pilosus, and the main
      constituents in MFBS were analyzed by HPLC analysis. In vitro, MFBSE were
      examined for anti-adipogenic effects using Oil-Red O staining. In vivo, mice were
      fed a normal-fat diet (NFD) control, HFD control or HFD containing 1 g/kg MFBSP
      for 12 weeks, and then body weight gain and tissues weight measured. Real-time
      PCR and western blot assay were used to determine the mechanism of anti
      adipogenic effects. RESULTS: MFBSE inhibited lipid accumulation in 3T3-L1
      adipocytes without exerting cell cytotoxicity. MFBSP treatment in HFD-fed mice
      significantly decreased the body weight gain compared with the HFD control mice.
      MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of
      adipogenesis-related genes, such as peroxisome proliferator-activated receptor
      gamma(PPAR gamma), fatty acid-binding protein 4 (FABP4), and fatty acid synthase
      (FAS), in adipocytes and in white adipose tissue (WAT) of HFD-induced obese mice.
      CONCLUSIONS: These results suggest that the anti-obesity effects of MFBS are
      elicited by regulating the expression of adipogenesis-related genes in adipocytes
      and WAT of HFD-induced obese mice.

PMID- 25975499
TI  - Antiprotozoal assessment and phenolic acid profiling of five Fumaria (fumitory)
      species.
AB  - OBJECTIVE: To explore some Fumaria species which were recorded to be
      traditionally used against malaria and other protozoal diseases. METHODS:
      Consequently, in the current study, antiprotozoal effect of the ethanol extracts
      obtained from five Fumaria species (Fumaria densiflora, Fumaria cilicica, Fumaria
      rostellata, Fumaria kralikii, and Fumaria parviflora) was investigated against
      the parasites; Plasmodium falciparum (malaria) and Trypanosoma bruceirhodesiense
      (human African trypanosomiasis) at 0.81 and 4.85 MUg/mL concentrations. RESULTS:
      Among them, Fumaria densiflora extract exerted the highest antiplasmodial
      (93.80%) and antitrypanasomal effect (55.40%), while the ethanol extracts of
      Fumaria kralikii (43.45%) and Fumaria rostellata (41.65%) showed moderate
      activity against Plasmodium falciparum. Besides, phenolic acid contents of the
      extracts were analyzed using high performance liquid chromatography (HPLC) and
      trans-cinnamic (4.32 mg/g) and caffeic (3.71 mg/g) acids were found to be the
      dominant phenolic acids in Fumaria densiflora. CONCLUSIONS: According to our
      results, Fumaria densiflora deserve further study for its promising antiprotozoal
      activity.

PMID- 25975500
TI  - Profile and geographical distribution of reported cutaneous leishmaniasis cases
      in Northwestern Saudi Arabia, from 2010 to 2013.
AB  - OBJECTIVE: To describe the profile and geographical distribution of reported
      cases of cutaneous leishmaniasis (CL) in the province of Hail, Saudi Arabia from
      2010 to 2013. METHODS: Human data were collected from the dermatology service of
      both King Khaled and General Hail hospitals. RESULTS: A total of 483 confirmed CL
      cases were investigated. Cutaneous leishmaniasis follows a seasonal distribution
      related to the activity of the phlebotomine sand fly fauna. Both saudi and non
      saudi patients were almost equally infected. The number of reported cases of CL
      in men was higher than that in females. The frequency of CL was asoociated with
      age and increased in teenager and adult group. By analyzing the geographical
      distribution, the majority of Hail districts were affected with this disease.
      However it is more prevalent in Hail city. CONCLUSIONS: The lack of data
      concerning the parasite, the sand fly fauna and the existing transmission cycles
      in Hail province make difficult to interpret the reported results and to follow
      up the spatio-temporal evolution of the disease.

PMID- 25975501
TI  - Change of MicroRNA-134, CREB and p-CREB expression in epileptic rat.
AB  - OBJECTIVE: To To investigate the changes of MicroRNA-134, CREB and p-CREB
      expression in epileptic rat brains in order to elucidate the molecular mechanisms
      of epilepsy, providing new ideas for clinical treatment. METHODS: Sixty-four
      Spraque-Dawley (SD) rats were divided into groups randomly, including control
      group, six hours after seizure group, 24-hour group, three-day group, one-week
      group, two-week group, four-week group, and eight-week group. All groups were
      placed under a pilocarpine-induced epilepsy model except the control group, and
      all rats were decapitated in different points of time. Brain specimens were taken
      for quantitative PCR experiments, immunohistochemistry and Western blot
      experiments. The results of the epilepsy model groups and the control group were
      compared. RESULTS: There were no significant differences between the six hours
      after seizure group, the 24-hour group and the control group about the MicroRNA
      134 levels. MicroRNA-134 in the hippocampus tissue of the three-day group
      significantly reduced compared with the control group; same result was observed
      with the one-week, two-week, four-week and eight-week groups. The CREB and p-CREB
      levels in the three-day group's rat hippocampus significantly increased compared
      with the control group; and the high levels of CREB and p-CREB were constantly
      maintained in the one-week, two-week, four-week and eight-week groups.
      CONCLUSIONS: The MicroRNA-134 level of the epileptic rat hippocampus is
      significantly lower than normal after three days, and continues to maintain a low
      level; while CREB and p-CREB levels are rsignificantly increased after three
      days, and continue to remain at a high level. MicroRNA-134 plays a role in
      inhibiting synaptic plasticity by inhibiting CREB and p-CREB expressions.

PMID- 25975502
TI  - Pharmacokinetic and pharmacodynamic analysis of ferulic acid-puerarin
      astragaloside in combination with neuroprotective in cerebral
      ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: To investigate the effects of the active ingredients combined therapy
      on inflammatory factors interleukin 1 beta (IL-1beta) and neuropeptide Y (NPY)
      based on pharmacodynamics in rats. METHODS: The animal model was built by
      transient middle cerebral artery occlusion (MCAO). The method for evaluating the
      concentrations of the FA-Pr-Al components in rat plasma was established by using
      HPLC and the expression levels of IL-1beta and NPY were determined by ELISA. A
      new mathematics method of the trend of percentage rate of change (PRC) was used
      to assess the correlation between pharmacokinetics (PK) and pharmacodynamics
      (PD). RESULTS: FA-Pr-Al in combination reduced neurological deficits, decreased
      infarct volume and inhibited the expression levels of IL-1beta and NPY (all
      P<0.05) compared with the model group. FA, Pr and Al all displayed two
      compartment open models in rats. Clockwise hysteresis loops were obtained by time
      concentration-effect curves. IL-1beta and NPY level changes in the plasma
      followed an opposite trend to the plasma concentration tendency after Cmax was
      reached. Astragaloside's PRC value was significantly higher than those of FA and
      puerarin between 120 to 180 min. CONCLUSIONS: The pharmacokinetics of FA-Pr-Al in
      combination were closely related its pharmacodynamics in treating
      ischemia/reperfusion injury, and the components of FA-Pr-Al may have a
      synergistic pharmacological effect. Astragaloside may play a more pronounced role
      in regulating IL-1betaand NPY levels compared with puerarin or FA.

PMID- 25975503
TI  - HSP90 and SIRT3 expression in hepatocellular carcinoma and their effect on
      invasive capability of human hepatocellular carcinoma cells.
AB  - OBJECTIVE: To vexplore expression of HSP90, SIRT3 in liver cancer tissue and its
      effect on liver cancer cell invasion ability. METHODS: Moderate expression of
      HSP90 in SMMC-7721, HepG2, LO2 and Hep-3B cell lines were screened, which was
      validated by RT-PCR. Over-expression of HSP90 cell line and lentivirus packaging
      HSP90-RNAi were established, which was validated by RT-PCR and western blot. The
      level of epithelial-mesenchymal transition (EMT) related gene was detected by
      western blot. The percentage of cancer stem cells was assayed by flow cytometry.
      RESULTS: RT-PCR demonstrated the highest expression of HSP90 mRNA in SMMC-7721
      cells, the lowest expression of HSP90 mRNA in Hep3B and LO2 and the moderate
      expression of HSP90 mRNA in Hep-G2. Therefore, HepG2 was selected as a follow-up
      experiment cell lines. Compared with the blank control group, expression of HSP90
      in HSP overexpression group was increased obviously, and expression of HSP90 in
      HSP90 shRNA group was significantly decreased, which indicated successful
      establishment of HSP overexpression and shRNA group. The apoptotic cell in hsp
      siRNA group was higher than the blank control group, while the HSP overexpression
      group showed opposite results. Western blot results showed transfection HSP
      promoted cells EMT transformation, up-regulated the level of E-cadherin, and down
      regulated the level of Vimentin; meanwhile, shRNA group showed opposite results.
      CONCLUSIONS: Carcinoma HepG2 cell transfected high expression of HSP can promote
      the transformation of EMT, improve the expression of Vimentin, reduce the
      expression of E-cadherin, and inhibit apoptosis of cancer stem cells, which
      improve the invasive ability of cancer of the liver cells. While hsp-siRNA group
      presents opposite results. In summary, the expression of HSP is closely related
      to the occurrence, development and invasion of cancer of the liver tissue.

PMID- 25975504
TI  - Relationship between arterial atheromatous plaque morphology and platelet
      associated miR-126 and miR-223 expressions.
AB  - OBJECTIVE: To study the expression of miR-126 and miR-223 in platelet of rabbit
      arterial plaque models, and explore its correlation with plaque morphology.
      METHODS: Rabbit arterial plaque models were established, peripheral blood of
      models and control animals was collected. Plaque morphologies were divided into
      type I, type II and type III based on angiography plaque morphology and Ambrose
      method. Platelet isolation kit was applied to isolate and purify peripheral blood
      platelets, CD45 immunomagnetic beads were used to remove the residual white blood
      cells. The miRNAs of platelets was extracted by miRNA Isolation Kit, and
      expressions of miR-126 and miR-223 of the platelets samples were detected by Real
      time PCR. The correlation between plaque morphology and platelet-associated miR
      126 and miR-223 expressions were analyzed. Expressions of target gene VCAM-1 and
      P2Y12 receptors of miR-126 and miR-223 in the atherosclerosis plaque of rabbit
      model were detected by Western blot. RESULTS: Relative expression levels of miR
      126 and miR-223 in the model group were 0.27+/-0.10 and 0.71+/-0.14,
      respectively. Plaque morphology was divided into types I, II and III; and miR-126
      and miR-223 expression levels were detected in each type. Expression levels of
      miR-126 in each type were 0.42+/-0.07, 0.17+/-0.11 and 0.22+/-0.15, respectively;
      and expression levels of miR-223 in each type are 0.68+/-0.02, 0.57+/-0.06 and
      0.88+/-0.10, respectively. Relative to the control group, miR-126 and miR-223
      known target genes in VCAM-1 and P2Y12 receptors increased platelets in rabbit
      atherosclerotic plaque models (P<0.05). CONCLUSIONS: Relative to normal control
      animals, miR-126 and miR-223 platelets were reduced in the rabbit atherosclerotic
      plaque model group (P<0.05). In the type II plaque morphology group, miR-126 was
      greatly reduced; and there is no significant correlation between miR-223 and
      plaque morphology.

PMID- 25975505
TI  - Transcatheter closure of ventricular septal defect in patients with aortic valve
      prolapse and mild aortic regurgitation: feasibility and preliminary outcome.
AB  - OBJECTIVE: To evaluate the feasibility, safety and efficacy of transcatheter
      closure of ventricular septal defect (VSD) in patients with aortic valve prolapse
      (AVP) and mild aortic regurgitation (AR). METHODS: Between January 2008 and July
      2014, transcatheter closure of VSD was attempted in 65 patients. RESULTS: The
      total intermediate closure successful rate in all subjects was 96.9%. During the
      perioperative period, no death, major bleeding, pericardial tamponade, occluder
      dislodgement, residual shunt or hemolysis occurred. Two procedures had been
      forced to suspend due to significant aggregation of device related aortic
      regurgitation, three cases of transient complete left bundle branch block
      occurred but did not sustain. At 1-year follow-up, no patients had residual
      shunts and complications. Furthermore, grade of residual AR were relieved in
      61.9% (39/63) cases and degree of AVP were ameliorated in 36.5% (23/63) patients;
      CONCLUSIONS: Transcatheter closure VSD in selected patients with AVP and mild AR
      is technically feasible and highly effective. Long term safety and efficacy needs
      to be assessed.

PMID- 25975506
TI  - Effects of gene silencing of CypB on gastric cancer cells.
AB  - OBJECTIVE: To determine the effect of gene silencing of cyclophilin B (CypB) on
      growth and proliferation of gastric cancer cells. METHODS: CypB siRNA lentivirus
      (LV-CypB-si) and control lentivirus (LV-si-con) were produced. CypB expression in
      gastric cancer cell lines was detected by Western blot. BGC823 and SGC7901 cells
      were chosen to be infected with LV-si-con and LV-CypB-si, and stable
      transfectants were isolated. The cell groups transfected with LV-CypB-siRNA, LV
      siRNA-con and transfected no carrier were served as the experimental group, the
      implicit control group and the blank control group respectively. MTT and colony
      formation assays were used to examine the effect of CypB on the cell growth and
      proliferation in vitro. Cell cycle was analyzed with flow cytometry. The
      expression of VEGFR of BGC823-si and SGC7901-si was detected by Western blot.
      RESULTS: Gene silencing of CypB can inhibit gastric cancer cell growth,
      proliferation, cell cycle progress and tumorigenesis. CypB expression level was
      obviously higher in SGC7901 and BGC823 than MKN28 and GES. These two cell lines
      were infected with LV-si-con and LV-CypB-si respectively. MTT and cloney
      formation assays showed a significantly decreased rate of cell proliferation from
      the forth day or the fifth day in cells transfected with LV-CypB-si (P<0.05).
      Down-regulation of CypB resulted in slightly decreased percentage of S phase and
      increased percentage of G1 (P<0.05). These findings indicated that CypB could
      promote the G1-S transition of gastric cancer cell. In addition, the expression
      of VEGF of BGC823 and SGC7901 transfected with CypB siRNA was reduced in
      comparison with the implicit control group and the blank control group.
      CONCLUSIONS: Gene silencing of CypB decreases gastric cancer cells proliferation
      and in vivo tumorigenesis. These findings indiccate CypB could be a potential
      biomarker and therapeutic target for gastric cancer.

PMID- 25975507
TI  - Microscopic study of ultrasound-mediated microbubble destruction effects on
      vascular smooth muscle cells.
AB  - OBJECTIVE: To observe vascular smooth muscle cell morphological changes induced
      by ultrasound combined with microbubbles by Atomic Force Acoustic Microscopy
      (AFAM). METHODS: A7r5 rat aortic smooth muscle cells were divided into groups:
      control group (without ultrasonic irradiation, no micro bubbles) and US+MB group
      (45 kHz, 0.4 W/cm(2) ultrasound irradiate for 20 seconds with a SonoVueTM
      concentration of [(56-140)*10(5)/mL]. Cell micro-morphological changes (such as
      topographic and acoustic prognosis) were detected, before and after ultrasound
      destruction by AFAM. RESULTS: In cell morphology, smooth muscle cells were spread
      o and connected to each another by fibers. At the center of the cell, the nuclear
      area had a rough surface and was significantly elevated from its surroundings.
      The cytoskeletal structure of the reticular nucleus and cytoplasm in the
      morphology of A7r5 cells (20 MU m * 20 MU m) were clear before microbubble
      intervention. After acoustic exciting, the cell structure details of the acoustic
      image were improved with better resolution, showing the elasticity of different
      tissues. In the acoustic image, the nucleus was harder, more flexible and uneven
      compared with the cytoplasm. Many strong various-sized echo particles were stuck
      on the rough nuclear membrane's substrate surface. The nuclear membrane did not
      have a continuous smooth surface; there were many obstructions (pores). After
      ultrasound-intervention was combined with microbubbles, the dark areas of the
      A7r5 cell images was increased in various sizes and degrees. The dark areas
      showed the depth or low altitudes of the lower regions, suggesting regional
      depressions. However, the location and scope of the acoustic image dark areas
      were not similar to those found in the topographic images. Therefore, it was
      likely that the dark areas, both from the topographic and acoustic images, were
      sound-holes. In addition, some cell nuclei become round in different degrees
      after irradiation. CONCLUSIONS: Atomic force microscopy and acoustic excitation
      method can noninvasively and completely display a cell's structure, connections
      and elastic properties at a nano scale in just several minutes. The dark areas,
      both from the topographic and acoustic images, may be sound-holes; therefore, it
      would be helpful if these sound-holes were found. These findings provide a
      relationship between cell apoptosis after ultrasound and microbubble ultrasound
      irradiation, and the sound-hole effect.

PMID- 25975508
TI  - Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese
      patients with nocturnal frontal epilepsy.
AB  - OBJECTIVE: To detect the CHRNA7 gene mutation and polymorphism in Southern Han
      Chinese patients with nocturnal frontal lobe epilepsy (NFLE). METHODS: Blood
      samples were collected from 215 Southern Han Chinese patients with NFLE and 200
      healthy Southern Han Chinese control subjects. Genomic DNA was extracted, and
      CHRNA7 whole genome exons were amplified by the polymerase chain reaction and
      subjected to Sanger sequencing. RESULTS: No CHRNA7 gene mutation was detected in
      all of the NFLE patients. However, five single nucleotide polymorphisms (SNPs) in
      sporadic cases were found, located in exons 5, 6, and 7 of the CHRNA7 gene. Among
      them, c.690G>A and c.698A>G are known SNPs, while c.370G>A, c.654C>T, and c.497
      498delTG were newly discovered SNPs. These SNPs were also found in some of the
      healthy controls. CONCLUSIONS: No CHRNA7 gene mutation was identified in Southern
      Han Chinese patients with NFLE. The CHRNA7 gene is probably not responsible for
      NFLE in this population.

PMID- 25975509
TI  - Liver cirrhosis and splenomegaly associated with Schistosoma mansoni in a
      Sudanese woman in Malaysia: A case report.
AB  - We report a case of a patient with Schistosoma mansoni infection who presented
      with liver cirrhosis and splenomegaly. She was diagnosed by a serological test
      and Kato-Katz thick smear stool examination. The patient was a 52-year-old woman
      from Sudan who came to Malaysia for a week to visit her sons. The patient lives
      in the middle of Rabak region, Sudan, a highly endemic area for schistosomiasis
      where her daily routine includes rearing of cows and farming. The site of toilet
      and sources of drinking water are canals and wells; both infested with snails.
      Patient had a long history of exposure and coming into contact with water from
      these canals and wells. 

PMID- 25975510
TI  - Glial fibrillary acidic protein: from intermediate filament assembly and gliosis
      to neurobiomarker.
AB  - Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) III
      protein uniquely found in astrocytes in the central nervous system (CNS), non
      myelinating Schwann cells in the peripheral nervous system (PNS), and enteric
      glial cells. GFAP mRNA expression is regulated by several nuclear-receptor
      hormones, growth factors, and lipopolysaccharides (LPSs). GFAP is also subject to
      numerous post-translational modifications (PTMs), while GFAP mutations result in
      protein deposits known as Rosenthal fibers in Alexander disease. GFAP gene
      activation and protein induction appear to play a critical role in astroglial
      cell activation (astrogliosis) following CNS injuries and neurodegeneration.
      Emerging evidence also suggests that, following traumatic brain and spinal cord
      injuries and stroke, GFAP and its breakdown products are rapidly released into
      biofluids, making them strong candidate biomarkers for such neurological
      disorders. 

PMID- 25975511
TI  - Increased incidence of nitroimidazole-refractory giardiasis at the Hospital for
      Tropical Diseases, London: 2008-2013.
AB  - Giardia intestinalis is the commonest gastrointestinal protozoal pathogen
      worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line
      treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure
      of treatment can occur in patients with hypogammaglobulinaemia or human
      immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms.
      There is little evidence to guide the clinical management of nitroimidazole
      refractory disease. We performed a retrospective audit of nitroimidazole
      refractory giardiasis in returned travellers at the Hospital for Tropical
      Diseases, London between 2011 and 2013. Seventy-three patients with microscopy
      proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were
      identified, and their management was investigated. In 2008, nitroimidazole
      treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to
      40.2% in 2013. Patient demographics remained stable during this period, as did
      routes of referral. Of patients with giardiasis, 39.0% had travelled to India;
      this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the
      patients with refractory disease, 44.6% had HIV serological investigations
      performed and 36.5% had immunoglobulin levels determined. Patients with
      refractory disease were treated with various agents, including albendazole,
      nitazoxanide, and mepacrine, alone or in combination. All 20 patients who
      received a mepacrine-containing regimen were cured. This data shows a worrying
      increase in refractory disease, predominantly in travellers from India, which is
      likely to represent increasing nitroimidazole resistance. Improved tools for the
      diagnosis of resistant G. intestinalis are urgently needed to establish the true
      prevalence of nitroimidazole-resistant giardiasis, together with clinical trials
      to establish the most effective second-line agent for empirical treatment
      regimens.

PMID- 25975512
TI  - Anti-inflammatory effect of Impatiens textori Miq. extract via inhibition of
      NLRP3 inflammasome activation in in vitro and in vivo experimental models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Impatiens textori Miq. (I. textori,
      Balsaminaceae) is a traditional medicinal herb used for centuries to treat
      several inflammatory related skin infections and allergic disorders in Asian
      countries. AIM OF THE STUDY: In this study, we elucidated the effects of whole
      plant extracts of I. textori on inflammasome activation using in vitro and in
      vivo models. MATERIALS AND METHODS: LPS-stimulated murine bone marrow macrophages
      were used to study the regulatory effect of I. textori extract (IT) on
      inflammasome activation. ATP, nigericin and MSU were used as danger-associated
      molecules to activate the NLRP3 inflammasome. An LPS-induced acute lung injury
      (ALI) mouse model was used to study the in vivo effect of IT on inflammasome
      activation. RESULTS: IT treated at 25, 50, and 100MUg/mL concentrations
      suppressed interleukin-1beta secretion through the attenuation of NLRP3
      inflammasome activation (p<0.001 at 100MUg/mL) leading to the decreased amount of
      ASC oligomerization and caspase-1 maturation. For the in vivo model, IT inhibited
      the NLRP3 expression and cell recruitment at the lung tissue in the ALI mouse
      model. CONCLUSION: IT exhibited potent anti-inflammatory effects via the
      attenuation of NLRP3 inflammasome activation supporting the traditional claims
      and may provide a valuable therapeutic strategy in treating various inflammation
      related disorders.

PMID- 25975513
TI  - Chromolaena odorata (L.) R.M. King & H. Rob. (Asteraceae) in sub-Saharan Africa:
      A synthesis and review of its medicinal potential.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaena odorata (L.) R.M. King & H. Rob.
      (Asteraceae) is a scrambling perennial shrub that originated in the Americas, but
      is now common in sub-Saharan Africa, Asia and Oceania, where it has become a
      serious weed. The species, particularly the biotype found in Asia and West
      Africa, has many ethnopharmacological uses, including treatment of malaria,
      wounds, diarrhoea, skin infection, toothache, dysentery, stomach ache, sore
      throat, convulsions, piles, coughs and colds. Furthermore, no attempt has been
      made to synthesise and review the available literature on the usefulness of the
      plant in the sub-Saharan African region, hence this paper examines the beneficial
      attributes of C. odorata in sub-Saharan Africa. MATERIAL AND METHODS: Published
      information on the species was gathered by the use of different database
      platforms, including Google Scholar, ScienceDirect, SciFinder and Scopus.
      RESULTS: Records indicate that two biotypes of C. odorata are present in sub
      Saharan Africa viz. the more widespread Asian/West African C. odorata biotype
      (AWAB) and the southern African biotype (SAB). While the usefulness of the former
      is well elucidated in the literature, such information on the latter is still
      scarce. Although the importance of AWAB C. odorata as a fallow species and as a
      soil fertility improvement plant in the slash and burn rotation system of
      agriculture in West Africa is increasingly being recognised, its usage in
      traditional medicinal practice is far more appreciated. The species has a wide
      range of ethnopharmacological uses, possibly because of the presence of
      flavonoids, essential oils, phenolics, tannins and saponins. The plant is
      reported to have antibacterial, anti-inflammatory, antioxidant, anthelminthic,
      antifungal, cytotoxic, anticonvulsant, antiprotozoal, antispasmodic, antipyretic
      and analgesic properties. CONCLUSION: While the results of this review suggest
      that the AWAB plant can be exploited as an alternative to other threatened plant
      species known to possess similar medicinal potential, the medicinal and
      pharmacological potential of the SAB plant remains to be established. Further
      studies on the phytochemistry and pharmacological properties of the SAB plants
      will not only advance our knowledge of ethnobotany and ethnomedicine, but may
      also improve the health and knowledge of the local people.

PMID- 25975514
TI  - Main plants used in traditional medicine for the treatment of snake bites n the
      regions of the department of Antioquia, Colombia.
AB  - ETHNOPHARMACOLOGY RELEVANCE: In Colombia, more than 4.000 ophidian accidents
      occur per year and due to the scarce distribution and limited availability of
      antivenom, the use of traditional medicine has been perpetuated in some of its
      rural communities, in which initially, those affected are treated by healers and
      shamans using medicinal plants in different ways. METHODS: Research was conducted
      with renowned healers or connoisseurs of plants on the ethnobotany of ophidian
      accidents in five different areas and their municipalities of Antioquia:
      Magdalena Medio (Caracoli, Puerto Berrio); Bajo Cauca (Caucasia, Zaragoza);
      Nordeste (San Roque, Yali); Norte (Gomez Plata, Valdivia); Suroeste (Ciudad
      Bolivar, Salgar); collecting information related to experience and time of use of
      plants in the treatment of these poisonings, amounts used, ways of use (beverage,
      bathing, ointment, chupaderas, vapors), preparation types (maceration or
      decoction) and treatment duration. RESULTS: 71 plant species were identified and
      collected, 49.29% of them without previous reports as antiophidian and 38.0%
      employed for the same purpose in other geographical areas. The leaves (24.82%),
      stems (11.68%) and flowers (10.95%) were found to be the most frequently employed
      structures in the preparation of the extracts, which are usually prepared by
      decoction (83.94%), maceration (6.57%). CONCLUSIONS: In this work, specimens
      lacking previous ethnobotanical reports have been found, plants used by ethnic
      groups from other regions of Antioquia and the world to treat snake bites; and
      herbaceous plants whose inhibitory activity of symptoms produced by some snake
      venoms, has been experimentally verified by in vivo and in vitro tests.

PMID- 25975515
TI  - Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human
      monocytes: Skew toward M2 macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willdenow ex Roemer &
      Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as "cat's
      claw", and traditionally used in folk medicine to deal with several inflammatory
      diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid
      (POA) from U. Tomentosa and has been reported to modify the inflammatory
      response. Herein, we have sought to identify the mechanisms underlying this
      modulatory effect of MTP on primary human monocytes and its ability to regulate
      differentiation processes on human primary monocyte and monocyte-derived
      macrophages. MATERIAL AND METHODS: In vitro studies with human primary monocytes
      and monocyte-derived macrophages were performed. Monocytes and M0 macrophages
      were exposed to MTP (25MUM) and LPS (100ng/mL). M0 macrophages were polarized to
      M1 and M2 phenotypes in the absence or presence of MTP. The activation state of
      monocytes/macrophages was assessed by flow cytometry, gene expression and protein
      analysis of different specific markers. RESULTS: In human primary monocytes, the
      incubation of MTP for 24h reduced the number of classical (CD14(++)CD16(-)) and
      intermediate (CD14(++)CD16(+)) subsets when compared to untreated or LPS-treated
      cells. MTP also reduced the chemotactic capacity of human primary monocytes. In
      addition, MTP promoted the polarization of M0 macrophages toward an anti
      inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory
      cytokines such as TNFalpha, IL-6 or IL-1beta, as well as the restoration of
      markers for M2 macrophages in LPS-treated M1 macrophages. CONCLUSIONS: Our
      results suggest that MTP may be a key modulator for regulating the plasticity of
      monocytes/macrophages and the attenuation of the inflammatory response.

PMID- 25975516
TI  - The anti-inflammatory activities of Ainsliaea fragrans Champ. extract and its
      components in lipopolysaccharide-stimulated RAW264.7 macrophages through
      inhibition of NF-kappaB pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ainsliaea fragrans Champ. (A. fragrans) is a
      traditional Chinese herbal that contains components like 3,5-dicaffeoylquinic
      acid and 4,5-dicaffeoylquinic acid. It exhibits anti-inflammatory activities
      which has been used for the treatment of gynecological diseases for many years in
      China. The aims of the present study were to investigate the anti-inflammatory
      activities of A. fragrans and elucidate the underlying mechanisms with regard to
      its molecular basis of action for the best component. MATERIALS AND METHODS: The
      anti-inflammatory effects of A. fragrans were studied by using lipopolysaccharide
      (LPS)-stimulated activation of nitric oxide (NO) in mouse RAW264.7 macrophages.
      Expression of inducible NO synthase (iNOS) and pro-inflammatory cytokines,
      inhibitory kappaBalpha (IkappaBalpha) degradation and nuclear translocation of NF
      kappaB p65 were further investigated. RESULTS: The present study demonstrated
      that A. fragrans could suppress the production of NO in LPS-stimulated RAW264.7
      macrophages. Further investigations showed A. fragrans could suppress iNOS
      expression. A. fragrans also inhibited the expression of tumor necrosis factor
      alpha and interleukin-6. A. fragrans significantly decreased the degradation of
      IkappaBalpha, reduced the level of nuclear translocation of p65. All these
      results suggested the inhibitory effects of A. fragrans on the production of
      inflammatory mediators through the inhibition of the NF-kappaB activation
      pathway. CONCLUSION: Our results indicated that A. fragrans inhibited
      inflammatory events and iNOS expression in LPS-stimulated RAW264.7 cells through
      the inactivation of NF-kappaB pathway. This study gives scientific evidence that
      validate the use of A. fragrans in treatment of patients with gynecological
      diseases in clinical practice in traditional Chinese medicine.

PMID- 25975517
TI  - The protective effect of eupafolin against TNF-alpha-induced lung inflammation
      via the reduction of intercellular cell adhesion molecule-1 expression.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eupafolin, a major bioactive compound found in
      Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell
      adhesion molecules in the lung airway epithelium is associated with the
      epithelium-leukocyte interaction and plays a critical role in the pathogenesis of
      lung airway inflammatory disorders. To investigate the effects of eupafolin on
      tumor necrosis factor-alpha (TNF-alpha)-induced intercellular cell adhesion
      molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the
      underlying mechanisms. MATERIALS AND METHODS: The effect of eupafolin on ICAM-1
      expression in A549 cells were examined by Western blotting and immunofluorescent
      staining. The mice were injected intraperitoneally with or without eupafolin and
      then were left untreated or were injected intratracheally with TNF-alpha. To
      detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also
      examined by Western blotting and immunohistochemical staining. RESULTS: Eupafolin
      pretreatment reduced the TNF-alpha-induced ICAM-1 expression and also the ERK1/2,
      JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1
      expression with TNF-alpha treatment was unaffected by p38 and PI3K inhibitors.
      Eupafolin decreased the TNF-alpha-induced NF-kappaB p65 activation and its
      nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the
      lung tissues of TNF-alpha-treated mice. CONCLUSIONS: Eupafolin exerts its anti
      inflammatory activity by suppressing the TNF-alpha-induced ICAM-1 expression and
      subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear
      translocation of NF-kappaB p65. These results suggest that eupafolin may
      represent a novel therapeutic agent targeting epithelial activation in lung
      inflammation.

PMID- 25975518
TI  - Berlin Editorial.

PMID- 25975519
TI  - Ultrasound-guided micropercutaneous nephrolithotomy in pediatric patients with
      kidney stones.
AB  - OBJECTIVE: To present the outcomes of ultrasound-guided micropercutaneous
      nephrolithotomy for the treatment of renal stones in pediatric patients. METHODS:
      Ultrasound-guided micropercutaneous nephrolithotomy was carried out on 25
      pediatric patients from June 2012 to October 2014. Micropercutaneous
      nephrolithotomy surgery was completed without the use of fluoroscopy in 19
      patients. Medical records were retrieved from our institutional database and
      retrospectively reviewed. Percutaneous puncture was carried out by an "all-seeing
      needle" in seven patients and by a 14-G intravenous cannula in 18 patients. After
      entering to the collecting system through an "all-seeing needle" or by
      Microsheath, the calculus was fragmented using a 273-micron holmium yttrium
      aluminium garnet laser. After the stone was fragmented to the smallest pieces
      possible, the operation was terminated. RESULTS: Single access was obtained in
      all patients using ultrasound guidance. The average age of the patients was 4.12
      +/- 5.33 years. The mean stone size was 13.45 +/- 3.11 mm. The mean operative
      time was 51.45 +/- 30.69 min. The mean duration of hospitalization was 3.18 +/-
      1.77 days. Treatment success was 92%. Two patients had residual fragments after
      the procedure; these patients were followed conservatively. A total of three
      minor complications were observed and all of them were managed conservatively.
      CONCLUSIONS: To our knowledge, this is the first study of ultrasound-guided
      micropercutaneous nephrolithotomy in the pediatric population. Our findings
      suggest that micropercutaneous nephrolithotomy can be safely carried out with
      ultrasound guidance in children by experienced hands, allowing to minimize risks
      associated with radiation exposure in this patient population.

PMID- 25975520
TI  - In vivo assessment of equine arteritis virus vaccine improvement by disabling the
      deubiquitinase activity of papain-like protease 2.
AB  - Arteriviruses are a family of positive-stranded RNA viruses that includes the
      prototypic equine arteritis virus (EAV) and porcine reproductive and respiratory
      syndrome virus (PRRSV). Although several vaccines against these viruses are
      commercially available there is room for improvement, especially in the case of
      PRRSV. The ability of arteriviruses to counteract the immune response is thought
      to decrease the efficacy of the current modified live virus vaccines. We have
      recently shown that the deubiquitinase (DUB) activity of EAV papain-like protease
      2 (PLP2) is important for the inhibition of innate immune activation during
      infection. A vaccine virus lacking PLP2 DUB activity may therefore be more
      immunogenic and provide improved protection against subsequent challenge than its
      DUB-competent counterpart. To test this hypothesis, twenty Shetland mares were
      randomly assigned to one of three groups. Two groups were vaccinated, either with
      DUB-positive (n=9) or DUB-negative (n=9) recombinant EAV. The third group (n=2)
      was not vaccinated. All horses were subsequently challenged with the virulent
      KY84 strain of EAV. Both vaccine viruses proved to be replication competent in
      vivo. In addition, the DUB-negative virus provided a similar degree of protection
      against clinical disease as its DUB-positive parental counterpart. Owing to the
      already high level of protection provided by the parental virus, a possible
      improvement due to inactivation of PLP2 DUB activity could not be detected under
      these experimental conditions. Taken together, the data obtained in this study
      warrant further in vivo investigations into the potential of using DUB-mutant
      viruses for the improvement of arterivirus vaccines. 

PMID- 25975521
TI  - gga-miR-9* inhibits IFN production in antiviral innate immunity by targeting
      interferon regulatory factor 2 to promote IBDV replication.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that contribute to the repertoire of
      host-pathogen interactions during viral infections. In the current study, miRNA
      analysis showed that a panel of microRNAs, including gga-miR-9*, were markedly
      upregulated in specific-pathogen-free (SPF) chickens upon infection with
      infectious bursal disease virus (IBDV); however, the biological function of gga
      miR-9* during viral infection remains unknown. Using a TCID50 assay, it was found
      that ectopic expression of gga-miR-9* significantly promoted IBDV replication. In
      turn, gga-miR-9* negatively regulated IBDV-triggered type I IFN production, thus
      promoting IBDV replication in DF-1 cells. Bioinformatics analysis indicates that
      the 3' untranslated region (UTR) of interferon regulatory factor 2 (IRF2) has two
      putative binding sites for gga-miR-9*. Targeting of IRF2 3'UTR by gga-miR-9* was
      determined by luciferase assay. Functional overexpression of gga-miR-9*, using
      gga-miR-9* mimics, inhibited IRF2 mRNA and protein expression. Transfection of
      the gga-miR-9* inhibitor abolished the suppression of IRF2 protein expression.
      Furthermore, IRF2 knockdown mediated the enhancing effect of gga-miR-9* on the
      type I IFN-mediated antiviral response. These findings indicate that inducible
      gga-miR-9* feedback negatively regulates the host antiviral innate immune
      response by suppressing type I IFN production via targeting IRF2. 

PMID- 25975522
TI  - Genetic characterisation of Porcine circovirus type 2 (PCV2) strains from feral
      pigs in the Brazilian Pantanal: An opportunity to reconstruct the history of PCV2
      evolution.
AB  - Since its discovery, Porcine circovirus type 2 has emerged as one of the most
      relevant swine infectious diseases, causing relevant economic losses for the pig
      industry. While four genotypes were identified, only three (PCV2a, PCV2b and
      PCV2d) are currently circulating and display a worldwide distribution. Another
      genotype, PCV2c, has been described only once in Danish archive samples collected
      between 1980 and 1990. In addition to commercial pigs, PCV2 has been demonstrated
      to infect wild boars and other wild species, which can potentially serve as a
      reservoir for domestic populations. In this study, eight sequences obtained from
      feral pigs in the Pantanal region (Mato Grosso do Sul State, Brazil) were
      compared with reference sequences and other Brazilian sequences, and the results
      revealed remarkable genetic diversity, with all four genotypes currently
      recognised being detected (PCV2a, PCV2b, PCV2c and PCV2d). This finding
      represents a remarkable discovery, as it is the first detection of PCV2c since
      1990 and the first-ever detection of PCV2c in live animals. The peculiar
      population history and ecological scenario of feral pigs in the Pantanal coupled
      with the complex, and still only partially known relationship of feral pigs with
      other PCV2 susceptible species (i.e., domestic pigs, wild boars and peccaries),
      open exciting questions concerning PCV2 origin and evolution. Overall, the
      results of the present study led us to form the following hypothesis: the PCV2
      strains found in feral pigs may be the last descent of the strains that
      circulated among European pigs in the past, or they may have infected these feral
      pigs more recently through a bridge species. 

PMID- 25975523
TI  - Analysis of incomplete excisions of basal-cell carcinomas after breadloaf
      microscopy compared with 3D-microscopy: a prospective randomized and blinded
      study.
AB  - Basal-cell carcinomas may show irregular, asymmetric subclinical growth. This
      study analyzed the efficacy of 'breadloaf' microscopy (serial sectioning) and
      three-dimensional (3D) microscopy in detecting positive tumor margins. Two
      hundred eighty-three (283) tumors (51.2%) were put into the breadloaf microscopy
      group; 270 tumors (48.8%) into the 3D microscopy group. The position of any
      detected tumor outgrowths was identified in clock face fashion. The time required
      for cutting and embedding the specimens and the examination of the microscopic
      slides was measured. Patient/tumor characteristics and surgical margins did not
      differ significantly. Tumor outgrowths at the excision margin were found in 62 of
      283 cases (21.9%) in the breadloaf microscopy group and in 115 of 270 cases
      (42.6%) in the 3D microscopy group, constituting a highly significant difference
      (p < 0.001). This difference held true with incomplete excision of fibrosing
      (infiltrative/sclerosing/morpheaform) tumors [32.9% in the breadloaf microscopy
      group and 57.5% in the 3D microscopy group (p = 0.003)] and also with solid
      (nodular) tumors [16.1 and 34.2%, respectively (p < 0.001)]. The mean overall
      examination time required showed no important difference. In summary, for
      detection of tumor outgrowths, 3D microscopy has almost twice the sensitivity of
      breadloaf microscopy, particularly in the situation of aggressive/infiltrative
      carcinomas. 

PMID- 25975525
TI  - Arguing collaboratively: Argumentative discourse types and their potential for
      knowledge building.
AB  - BACKGROUND: There is growing interest in using argumentative discourse in
      educational settings. However, in a previous study, we found that discourse goals
      (persuasion vs. consensus) while arguing can affect student outcomes in both
      content learning and reasoning. AIMS: In this study, we look at argumentative
      discourse data from a previous study to ask how differences in discourse might
      account for the differences we observed in learning and reasoning outcomes.
      SAMPLE: One hundred and five dialogues (57 disputative, 48 consensus) between 7th
      grade science students attending a public high school near Tarragona, Spain.
      METHODS: Participants were randomly assigned to conditions and paired with peers
      who disagreed with them on three topics related to renewable energy sources.
      After instruction on each topic, they were asked to either 'argue to convince'
      (persuasion condition) or 'argue to reach consensus' (consensus condition) on
      that topic. Conversations were audio-recorded and transcribed for analysis.
      RESULTS: Students in the persuasion condition engaged in shorter conversational
      exchanges around argumentative claims and were more likely to use moves that
      foreclosed discussion, whereas students in the consensus condition were more
      likely to use moves that elicited, elaborated on, and integrated their partners'
      ideas. CONCLUSIONS: When arguing to reach - rather than defend - a conclusion,
      students are more likely to coconstruct knowledge by exchanging and integrating
      arguments. These findings are consistent with predictions about the potential of
      argumentation for knowledge building and suggest that teachers must attend to
      discourse goals when using argumentation to support learning and reasoning.

PMID- 25975526
TI  - Refractory choledocholithiasis treated with combination of ERCP and percutaneous
      biliary laser lithotripsy with flexible ureteroscope.

PMID- 25975524
TI  - Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol
      drinking in C57BL/6J mice.
AB  - Binge ethanol drinking is a highly pervasive and destructive behavior yet the
      underlying neurobiological mechanisms remain poorly understood. Recent work
      suggests that overlapping neurobiological mechanisms modulate feeding disorders
      and excessive ethanol intake, and converging evidence indicates that the
      melanocortin (MC) system may be a promising candidate. The aims of the present
      work were to examine how repeated binge-like ethanol drinking, using the
      'drinking in the dark' (DID) protocol, impacts key peptides within the MC system
      and if site-specific manipulation of MC receptor (MCR) signaling modulates binge
      like ethanol drinking. Male C57BL/6J mice were exposed to one, three or six
      cycles of binge-like ethanol, sucrose or water drinking, after which brain tissue
      was processed via immunohistochemistry (IHC) for analysis of key MC peptides,
      including alpha-melanocyte stimulating hormone (alpha-MSH) and agouti-related
      protein (AgRP). Results indicated that alpha-MSH expression was selectively
      decreased, while AgRP expression was selectively increased, within specific
      hypothalamic subregions following repeated binge-like ethanol drinking. To
      further explore this relationship, we used site-directed drug delivery techniques
      to agonize or antagonize MCRs within the lateral hypothalamus (LH). We found that
      the nonselective MCR agonist melanotan-II (MTII) blunted, while the nonselective
      MCR antagonist AgRP augmented, binge-like ethanol consumption when delivered into
      the LH. As these effects were region-specific, the present results suggest that a
      more thorough understanding of the MC neurocircuitry within the hypothalamus will
      help provide novel insight into the mechanisms that modulate excessive binge-like
      ethanol intake and may help uncover new therapeutic targets aimed at treating
      alcohol abuse disorders.

PMID- 25975527
TI  - Clip closure of defect after endoscopic resection in patients with larger
      colorectal tumors decreased the adverse events.
AB  - BACKGROUND: Clip closure of large colorectal mucosal defects may reduce the rate
      of adverse events in a cost-effective manner. OBJECTIVE: To assess the adverse
      events and outcomes of clip closure of defects after endoscopic resection in
      patients with large colorectal tumors. DESIGN: Prospective, randomized,
      controlled study. SETTING: Single tertiary referral center. PATIENTS AND
      INTERVENTIONS: Patients with lesions measuring 1 to 4 cm who were scheduled for
      endoscopic resection between March 2012 and December 2014 were randomly assigned
      to a clip-closure group and a no-closure group. In the clip-closure group, the
      defect of the resection site was completely closed with an endoclip. In the no
      closure group, the defect was left open. The following primary outcome measures
      were assessed: delayed postoperative bleeding, postpolypectomy coagulation
      syndrome, perforation, and abdominal pain. Secondary outcome measures of length
      of hospital stay, time required for procedure, and patient's satisfaction were
      also assessed. RESULTS: Patients and lesions had similar characteristics across
      both groups. For patients who underwent clip closure (n = 174), the rates of
      delayed postoperative bleeding (1.1% [2/174]) and postpolypectomy coagulation
      syndrome (0.6% [1/174]) were lower than those in the no-closure group (6.9%
      [12/174], P = .01 and 4.6% [8/174], P = .03). Two patients experienced
      perforation, 1 in each group. In the clip-closure group, 4 patients reported
      abdominal pain as opposed to 26 in the no-closure group (2.8% vs 16.7%, P < .01).
      The procedure took longer in the closure group (38.1 minutes vs 30.9 minutes, P =
      .04). The length of hospitalization was shorter in the closure group (3.1 days vs
      4.7 days, P = .03). Total medical expense was similar between the 2 groups.
      Patients who underwent closure reported greater satisfaction. LIMITATION: This
      was a single-center analysis. CONCLUSIONS: Clip closure of endoscopic resection
      defects in patients with large colorectal tumors decreased the rate of procedure
      related adverse events and did not increase the cost of hospitalization.

PMID- 25975528
TI  - Endoscopic submucosal dissection using a stag beetle knife for early esophageal
      cancer in lower esophageal diverticula.

PMID- 25975530
TI  - Endoscopic transhepatic cholangiography with antegrade transanastomotic stent
      placement in a liver transplantation patient with Roux-en-Y hepaticojejunostomy.

PMID- 25975529
TI  - A Japanese prospective multicenter study of self-expandable metal stent placement
      for malignant colorectal obstruction: short-term safety and efficacy within 7
      days of stent procedure in 513 cases.
AB  - BACKGROUND: Endoscopic self-expandable metal stent placement has been used as an
      alternative to surgery for malignant colorectal obstruction; however, factors
      affecting its clinical outcome are unclear. OBJECTIVE: To clarify the short-term
      safety and efficacy of endoscopic self-expandable metal stent placement for
      malignant colorectal obstruction and to identify factors associated with its
      clinical and technical failure. DESIGN: Prospective clinical cohort study.
      SETTING: Fourteen academic centers and 32 community hospitals. PATIENTS: A total
      of 513 consecutive patients with malignant colorectal obstruction. INTERVENTION:
      Endoscopic self-expandable metal stent placement, sharing of stent placement
      methods among participating facilities. MAIN OUTCOME MEASUREMENTS: The primary
      endpoint was clinical success, defined as symptom and radiological finding
      resolution within 24 hours. Secondary endpoints were technical success and
      adverse events. The follow-up period was 7 days. RESULTS: The clinical and
      technical success rates were 95.5% and 97.9%, respectively. Major adverse events
      included perforation (2.1%), stent migration (1.0%), and stent occlusion (0.8%).
      The main causes of perforation were the procedure itself (0.8%) and comorbidities
      (obstructive colitis and impending perforation) not apparent before stent
      placement (0.6%). Extrinsic tumor origin was independently associated with the
      clinical failure after stent placement (odds ratio 4.23; 95% confidence interval,
      1.21-14.79; P = .02). Stricture marking trended toward a negative association
      with technical failure (P = .09). LIMITATIONS: Noncomparative study. CONCLUSION:
      Strict inclusion criteria and stricture marking may improve the technical and
      clinical success of stent placement.

PMID- 25975531
TI  - Periprocedural management of aspirin during colonoscopy: a survey of practice
      patterns in the United States.
AB  - BACKGROUND: The risk of postpolypectomy bleeding for patients taking aspirin is
      low, and gastroenterology society guidelines state that aspirin is likely safe to
      continue; however, many practices recommend aspirin discontinuation. OBJECTIVE:
      To characterize practice patterns of periprocedural aspirin use with colonoscopy
      in the United States. DESIGN: Survey study. SETTING: Endoscopy units in the
      United States. INTERVENTIONS: We reviewed colonoscopy preparation instruction
      sheets available online to characterize recommendations regarding periprocedural
      aspirin use. The endoscopy units that recommended discontinuation of aspirin
      before colonoscopy were contacted to determine their reasons for doing so. We
      also determined which endoscopy units were recognized by the American Society for
      Gastrointestinal Endoscopy (ASGE) quality recognition program. MAIN OUTCOME
      MEASUREMENTS: Endoscopy unit recommendations regarding aspirin use before
      colonoscopy. RESULTS: We reviewed colonoscopy preparation instructions from 317
      endoscopy units, of which 138 (43.5%) recommended continuing aspirin, 103 (32.5%)
      recommended stopping aspirin, and 76 (24%) requested patients to contact a
      physician. The most common reasons for recommending aspirin discontinuation were
      concern about bleeding after polypectomy (62%), perceived minimal downside to
      stopping aspirin (38%), inertia to changing old policies (20%), and concern about
      medicolegal implications of postpolypectomy bleeding (15%). There was no
      significant association between endoscopy unit recommendations about
      periprocedural aspirin use and ASGE quality certification (P = .17) or type of
      endoscopy facility (ambulatory surgical center vs hospital affiliated) (P = .55).
      LIMITATION: Non-response bias. CONCLUSION: Less than half of the endoscopy units
      surveyed in the United States routinely continue aspirin before screening
      colonoscopies despite evidence that benefits outweigh the risks. It is important
      for gastroenterology and cardiology societies to make a firm statement, educate
      their members, and give them confidence and support to continue aspirin
      periprocedurally.

PMID- 25975532
TI  - Canopy interactions and physical stress gradients in subtidal communities.
AB  - Species interactions are integral drivers of community structure and can change
      from competitive to facilitative with increasing environmental stress. In
      subtidal marine ecosystems, however, interactions along physical stress gradients
      have seldom been tested. We observed seaweed canopy interactions across depth and
      latitudinal gradients to test whether light and temperature stress structured
      interaction patterns. We also quantified interspecific and intraspecific
      interactions among nine subtidal canopy seaweed species across three continents
      to examine the general nature of interactions in subtidal systems under low
      consumer pressure. We reveal that positive and neutral interactions are
      widespread throughout global seaweed communities and the nature of interactions
      can change from competitive to facilitative with increasing light stress in
      shallow marine systems. These findings provide support for the stress gradient
      hypothesis within subtidal seaweed communities and highlight the importance of
      canopy interactions for the maintenance of subtidal marine habitats experiencing
      environmental stress. 

PMID- 25975534
TI  - Sliding organs sign in gynecological ultrasound.

PMID- 25975533
TI  - Expansion of NK cells from PBMCs using immobilized 4-1BBL and interleukin-21.
AB  - Adoptive transfer of NK cells has been widely applied clinically for cancer
      immunotherapy. However, the difficulties to obtain a large number of activated NK
      cells impede the successful application of such therapy. In the present study, we
      implemented a novel method involving the use of immobilized human 4-1BBL and
      interleukin-21 to amplify NK cells from the peripheral blood mononuclear cells
      (PBMCs) of healthy donors. Following stimulation for 21 days, we achieved
      considerable expansion of NK cells with high purity and strong cytotoxicity. This
      is the first time solid phase cytokines were used to augment NK cells, and this
      method has the advantage of no need to introduce feeder cells, without prior
      purification of NK cells and it effectively stimulated and expanded NK cells. The
      strategy of cell proliferation and activation could lead to a safer and more
      effective application of NK cells clinically.

PMID- 25975535
TI  - Ratiometric Monitoring of Intracellular Drug Release by an Upconversion Drug
      Delivery Nanosystem.
AB  - Nanoscale drug delivery systems have been widely investigated due to their well
      recognized advantages including controlled delivery of chemotherapeutic agents,
      enhanced therapeutic effectiveness, and reduced adverse effects compared to
      conventional chemotherapy with small molecules. However, further progress in the
      use of nanoscale delivery systems in clinical applications has been hampered by
      pharmacokinetic studies in biological samples which were associated with
      significant experimental challenges. Here, we report a rational ratiometric
      approach to monitor drug release kinetics by quantitatively investigating
      luminescence resonance energy transfer (LRET) from upconversion nanoparticles to
      the antitumor drug doxorubicin (DOX). Specifically, DOX molecules within the
      shell of mesoporous silica-coated upconversion nanoparticles selectively quenched
      the green emission of upconversion nanoparticles, while the intensity of red
      emission was essentially unaltered. Consequently, when DOX was gradually
      released, a steady recovery of green emission was observed. The ability to
      monitor the intensity ratio of green-to-red luminescence enabled a rational
      design for real-time investigation of drug delivery release kinetics.
      Importantly, the internal standard effect of red emission made this ratiometric
      approach suitable for complex biological microenvironments. 

PMID- 25975537
TI  - [Heritability of body mass index on Chinese adult twins from nine
      provinces/cities in China].
AB  - OBJECTIVE: To explore the heritability of body mass index (BMI) in twins across
      different regions and genders in China. METHODS: A total of 11 122 adult twin
      pairs from the Chinese National Twin Registry were interviewed. A structural
      equation model was used to estimate the heritability of BMI. RESULTS: This study
      included 6 226 monozygotic twin pairs and 4 896 dizygotic twin pairs, with the
      age range as 25-85 (39.0 +/- 10.8) years. Under stratified analysis by region,
      results showed that the highest and lowest rates on heritability of BMI in men
      were seen in Tianjin and Zhejiang, as 67.8% (95% CI: 50.1%-85.8%) and 42.1% (95%
      CI: 27.2%-60.9%), while in women were seen in Sichuan and Heilongjiang as 56.2%
      (95% CI: 47.5%-70.0%) and 11.2% (95% CI: 0.0%-31.7%), respectively. Results from
      the stratified analysis showed that, by gender, the heritability of BMI in men
      was higher than that in women from the same region. The biggest differences of
      heritability of BMI between men and women were seen in Heilongjiang as 55.3% (95%
      CI: 35.5%-80.0%) and 11.2% (95% CI: 0-31.7%), while the smallest differences were
      seen in Sichuan as 61.5% (95% CI: 40.7%-86.4%) and 56.2% (95% CI: 47.5%-70.0%),
      respectively. CONCLUSION: The heritability of BMI across different regions and
      genders showed certain differences in the Chinese twins.

PMID- 25975538
TI  - [A survey on the condition of bike lanes in 12 cities, China].
AB  - OBJECTIVE: To explore the condition on bike lanes and the relationship with GDP
      of the related cities, residential of regions and prosperity of streets in 12
      selected cities in China. METHODS: Eexistence and maintenance of bike lanes were
      examinedin in all the streets under survey in 333 blocks of 12 cities (Beijing,
      Tianjin, Shanghai, Qingdao, Hangzhou, Shaoxing, Suzhou, Nantong, Zhenjiang,
      Chengdu, Xining and Harbin). Data were collected on GDP of the related cities,
      together with the sizes of population and proportion of the 333 blocksand the
      numbers of stores and restaurants in those streets. RESULTS: A total of 4 202
      streets were included in the study. In the 12 cities, 32.6% of the streets were
      equipped with bike lanes. Bike-lane-equipmentsseemed better in Nantong (46.5%),
      Tianjin (39.6%) and Shanghai (39.4%), but the scores were lower in Xining (2.0%),
      Qingdao (5.4%), and Harbin (27.1%). The higher GDP was, the better bike lanes
      were equipped. In the meantime, the isolation of bike lanes were worse and the
      streets more crowded. Density of the residential area was negatively correlated
      with the score on bike lane-equipments. CONCLUSION: Differences of the condition
      of bike lanes in the 12 cities indicated that improvement should be made on bike
      lanes. More attention should be paid to those cities with high GDPs and crowded
      residential regions on setting up the isolated bike lanes and reasonable
      equipments.

PMID- 25975539
TI  - [Exposure to tobacco advertisement and promotion programs among Chinese middle
      school students: a cross-sectional survey].
AB  - OBJECTIVE: To exam the exposure status to tobacco advertisement and promotion
      programs in Chinese middle school students. METHODS: Stratified multi-stage
      cluster sampling was used to select participated grade 7-9 middle school students
      in 31 provinces (n = 155 117). A self-administrated questionnaire was used in
      which questions related to behavior on tobacco use, exposure to second-hand
      smoking (SHS), access to tobacco products and prices, tobacco control advocacy,
      exposure to tobacco advertisement, and promotion as well as attitude and
      knowledge towards tobacco, etc. Data was weighted and analyzed, using the complex
      survey module of SAS 9.3 software. RESULTS: In the past 30 days, 48.5% of the
      students had a chance to see advertisement or promotion programs on tobacco.
      Tobacco advertisement or promotion were most frequently seen on TV (21.3%) among
      students, followed by outdoor billboard (20.1%), at the stands for sale (17.5%),
      and Internet (15.6%). In addition, 4.6% of the students reported having kept the
      items related to brand logos of tobacco products; 2.0% reported having been
      offered a free tobacco product by tobacco company representatives; 69.7% reported
      having seen scenes related to smoking on TV/videos/movie screens. Twenty five
      point two percent of the student smokers reported buying individual sticks at
      last purchase. Among those students who had never been exposed to tobacco, the
      ones who had been exposed to tobacco advertisement and promotion programs
      reported that they were more likely to feel smoking attractive than those who had
      not. They also reported that if a cigarette was offered by friends, they might
      try to smoke within the next 12 months, feeling that smoking would make him/her
      comfortable, and finally to feel that they might enjoy smoking (P < 0.000 1).
      CONCLUSION: Adolescents had been heavily exposed to tobacco advertisement and
      promotion programs in China. Students who had been exposed to tobacco
      advertisement or promotions were more likely to express positive attitude to
      tobacco use. It is urgent to make amendments to China's Advertising Law to
      completely prohibit tobacco advertisement, promotion and sponsorship programs, to
      keep the young people away from tobacco.

PMID- 25975536
TI  - Ceramide metabolism regulates autophagy and apoptotic cell death induced by
      melatonin in liver cancer cells.
AB  - Autophagy is a process that maintains homeostasis during stress, although it also
      contributes to cell death under specific contexts. Ceramides have emerged as
      important effectors in the regulation of autophagy, mediating the crosstalk with
      apoptosis. Melatonin induces apoptosis of cancer cells; however, its role in
      autophagy and ceramide metabolism has yet to be clearly elucidated. This study
      was aimed to evaluate the effect of melatonin administration on autophagy and
      ceramide metabolism and its possible link with melatonin-induced apoptotic cell
      death in hepatocarcinoma (HCC) cells. Melatonin (2 mm) transiently induced
      autophagy in HepG2 cells through JNK phosphorylation, characterized by increased
      Beclin-1 expression, p62 degradation, and LC3II and LAMP-2 colocalization, which
      translated in decreased cell viability. Moreover, ATG5 silencing sensitized HepG2
      cells to melatonin-induced apoptosis, suggesting a dual role of autophagy in cell
      death. Melatonin enhanced ceramide levels through both de novo synthesis and acid
      sphingomyelinase (ASMase) stimulation. Serine palmitoyltransferase (SPT)
      inhibition with myriocin prevented melatonin-induced autophagy and ASMase
      inhibition with imipramine-impaired autophagy flux. However, ASMase inhibition
      partially protected HepG2 cells against melatonin, while SPT inhibition
      significantly enhanced cell death. Findings suggest a crosstalk between SPT
      mediated ceramide generation and autophagy in protecting against melatonin, while
      specific ASMase-induced ceramide production participates in melatonin-mediated
      cell death. Thus, dual blocking of SPT and autophagy emerges as a potential
      strategy to potentiate the apoptotic effects of melatonin in liver cancer cells.

PMID- 25975540
TI  - [Associations between adverse childhood experiences with early puberty timing and
      possible gender difference].
AB  - OBJECTIVE: To explore the association of adverse childhood events with early
      puberty timing and possible gender differences. METHODS: Data was gathered
      through questionnaires, physical and secondary sexual characteristics,
      examination with breast stage in girls and testicular volume in boys measured
      under informed consent among children in grade 3 to grade 5 from a large-scale
      primary school. Information regarding adverse childhood experiences (ACEs), time
      of screening and physical activity was included in the questionnaire. Age limits
      on secondary sexual characteristics for defining early puberty established under
      the "China Puberty Research Collaboration Project" were used to classify early
      puberty timing. Body mass index was calculated and used to classify both
      overweight and obesity, in each gender. RESULTS: Among the 1 744 children aged
      8.2-12.2 years old (957 boys), the prevalence rates of early puberty timing among
      boys and girls were 7.5% and 14.6%, respectively, with gender differences (chi2 =
      11.671, P < 0.001). Boys who reported having experienced serious adverse family
      events and girls with physical abuse were more likely to develop early puberty.
      Results from multivariate logistic regression analysis showed that family life
      events were associated with a higher risk of early puberty timing in boys (odds
      ratio: 2.531, 95% CI: 1.276-5.020) while experience related to physical abuse
      appeared a risk factor of early puberty timing in girls (odds ratio: 2.453, 95%
      CI: 1.588-3.788). CONCLUSION: Physical abuse and adverse family life events
      seemed to be associated with early puberty timing, suggesting further
      longitudinal study should be carried out to understand the nature of these
      findings and gender differences.

PMID- 25975541
TI  - [Correlation between parameters on the shape of body and dissatisfaction against
      it from parents among children and adolescents].
AB  - OBJECTIVE: To analyze the correlation between children and adolescents' body
      shape parameters and parent's dissatisfaction on it. METHODS: Stratified cluster
      sampling method was used to select students and their parents, and height,
      weight, waist circumference (WC), hip circumference (HC), skinfold thichness of
      the students were measured. Body image from parents was studied through the 'Ma
      body figural shape'. Correlation between body shape parameters and
      dissatisfaction towards them from the parents was analyzed under both simple- and
      multiple-level methods. RESULTS: The overall prevalence of dissatisfaction on
      body-shapes from parents was 69.0%, including 28.6% of the parents expecting
      children to be fat (PEBF) while, 40.4% of the parents expecting their children to
      be thin (PEBT). In males, parameters as height, weight, WC, HC, skin fold
      thickness, BMI in PEBT were 1.9 cm, 11.9 kg, 13.2 cm, 8.8 cm, 32.3 mm, 4.7 kg/m2
      respectively, all higher than the satisfaction from the parents (PBIS) (all P <
      0.05), and these parameters were 2.3 cm, 7.1 kg, 7.2 cm, 5.8 cm, 14.1 mm, 2.3
      kg/m2 higher in PBIS than that of PEBF, respectively (all P < 0.05). In females,
      parameters as weight, WC, HC, skinfold thickness, BMI in PEBT appeared to be 8.6
      kg, 9.1 cm, 6.6 cm, 21.9 mm, 3.5 kg/m2 higher than that of PBIS (all P < 0.01),
      and were 5.5 kg, 5.9 cm, 5.4 cm, 10.4 mm, 1.8 kg/m2 higher in PBIS than that of
      PEBF, respectively, plus the difference of height was 3.6 cm more (P < 0.01).
      Differences of body shape on parameters between PEBT and PBIS were larger in
      primary school students than in middle school students. However, the differences
      of body shape parameters between PBIS and PEBF appeared higher in middle school
      students than in primary school male students, but were higher in female students
      in primary than in middle school students. CONCLUSION: The prevalence of body
      dissatisfaction related to children and adolscents' body shape parameters from
      parents was high. Parents in the PEBT group seemed to have paid more attention to
      children's body shape parameters at low age. However, parents in PEBF group might
      have paid more attention to children's body shape parameters at high age in males
      or at low age in females.

PMID- 25975542
TI  - [HIV/AIDS cases detection in medical institutions from 2008 to 2013 in China].
AB  - OBJECTIVE: To assess the detection of HIV/AIDS cases in medical institutions in
      China from 2008 to 2013. METHODS: 'Provider-initiated Opt-out HIV testing and
      counseling' method was offered to patients who met the needs for preoperation,
      perinatal examination, at the sexually transmitted disease (STD) clinic or other
      types of testing services. RESULTS: From 2008 to 2013, the number of HIV
      screening tests offered in medical institutions increased by 206.8%, from 24.94
      million to 76.54 million. The number of diagnosed HIV cases increased by 149.8%,
      from 18 241 to 45 560. HIV positive coarse rate showed a slight decrease, from
      7.3 per ten thousand in 2008 dropped to 6.0 per ten thousand in 2013. The HIV
      positive rate detected at the STD clinics or from other attendants showed a
      gradual decrease in 2009 and remained relatively stable. HIV positive rates
      showed at the programs as preoperative testing, regular screening programs on
      blood products, on pretreatment-regular-blood-testing or through perinatal
      examination, maintained at low levels. Proportions of case detection at medical
      institutions increased annually from 2008 to 2013 (32.4%, 36.0%, 40.2%, 45.3%,
      47.9% and 50.6% respectively) in China. Among them, the proportion of case
      detection via other types of testing services appeared over 50%. Over 20% of the
      HIV cases were identified via preoperative testing. CONCLUSION: Significant
      effects were seen through programs as offering Provider-initiated HIV testing and
      counseling to patients that receiving testing at the STD clinics or through other
      types of testing services. Opt-out HIV testing and counseling should be
      routinized in all the HIV related divisions in medical institutions.

PMID- 25975543
TI  - [Analysis on the individual-response behavior and the influence factors to
      violent terrorist attacks among undergraduates in Guangzhou].
AB  - OBJECTIVE: To analyze related behaviors of individual preparedness and
      influencing factors on violent terrorist attacks among undergraduates. METHODS: A
      total of 1 800 undergraduates from 5 colleges or universities in Guangzhou were
      selected, using the stratified cluster method. A questionnaire involving the
      response to violent terrorist attack behavior was used to assess the individual
      preparedness behaviors among undergraduates. A self-made questionnaire was
      applied to collect information on demographic factors, cognitive and preparedness
      behaviors. RESULTS: The mean score of individual preparedness behavior among
      undergraduates was 13.49 +/- 5.02 while information on seeking behavior was 4.27
      +/- 1.64, avoidance behavior was 5.97 +/- 2.16 and violent terrorist attack
      response behaviors was 23.73 +/- 7.21, with 30.0 percent of undergraduates
      behaved properly. Significant differences were found in the scores of behaviors
      on the response to violent terrorist attack with different gender, major they
      pursue or religious belief (P < 0.05), among undergraduates involved in this
      study. Results from the logistic regression analysis revealed that persons being
      girls (OR = 1.46, 95% CI: 1.06-2.01), with bigger perceived probability (OR =
      1.60, 95% CI: 1.12-2.30), with higher alertness (OR = 3.77, 95% CI: 2.15-6.61),
      with stronger coping confidence (OR = 0.34, 95% CI: 0.24-0.48) and bigger
      affective response (OR1 = 3.42, 95% CI: 2.40-4.86; OR2 = 0.23, 95% CI: 0.13
      0.41), would present more prominent behavior responses when facing the violent
      terrorist attack. CONCLUSION: Individual response behaviors to violent terrorist
      attacks among undergraduates were relatively ideal. Perceived probability,
      alertness, coping confidence and affective response appeared to be independent
      influencing factors related to response behaviors against violent terrorist
      attack. In colleges and universities, awareness on violent terrorist attacks
      should be strengthened among undergraduates. Focus should target on psychological
      education dealing with disaster, knowledge and skills needed for emergency
      response, so as to respond to the emergency on campus.

PMID- 25975544
TI  - [Impacts of hypertension on early changes of cardiovascular structure and
      function among children: a case-control study].
AB  - OBJECTIVE: To assess the cardiovascular structure and function in children with
      confirmed primary hypertension, and to explore the impact of hypertension and
      related risk factors on cardiovascular structure and function of children.
      METHODS: Parameters related to cardiac structure, vascular structure and function
      were measured in 213 hypertensive children, who were confirmed upon repeated
      measurements on separate occasions. A total of 197 healthy children were
      recruited as controls. RESULTS: 1) In hypertensive children, left ventricular end
      diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left
      ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular
      posterior wall thickness (LVPT) and interventricular septal thickness (IVST) were
      all significantly higher than their counterparts (P < 0.05). No statistical
      differences were found in carotid intima-media thickness (cIMT), relative wall
      thickness (RWT) and brachial ankle pulse wave velocity (ba-PWV). 2) Compared with
      controls, LVEDd, LVESd, LVM, LVMI were all significantly higher in hypertensive
      children (P < 0.05), regardless of age group or weight-status. No statistical
      differences were found in ccIMT and RWT, while ba-PWV was statistically higher in
      controls among children aged 6-12 years. 3) Data from multiple linear regression
      analysis noticed that LVMI was associated with age, sex, BMI and hypertension
      while RWT was associated with age and BMI. CONCLUSION: In children with primary
      hypertension, changes of vascular structure and function were not shown but left
      ventricular remodeling and early changes of function had been developed in
      children under 12 years old.

PMID- 25975545
TI  - [Study on the change of unsafe sexual behaviors and its determinants in HIV
      positive persons after being notified as HIV seropositive].
AB  - OBJECTIVE: To study the change of unsafe sexual behaviors and its determinants in
      HIV-positive persons after being notified as HIV seropositive. METHODS:
      Questionnaires were employed in HIV-positive persons whose testing results being
      notified over 1 year in Changsha and Hengyang between March 2013 and July 2013.
      RESULTS: Interview was carried out on 268 HIV-positive persons who reported
      having considerable variability in unsafe sexual behaviors. The incidence of
      unsafe sexual behaviors declined from 98.8% to 12.7% after being notified as HIV
      seropositive. Risk factors related to unsafe sexual behaviors after the
      notification would include gender (men OR = 0.443, 95% CI: 0.209-0.937) and
      living with sexual partner (OR = 2.549, 95% CI: 1.053-6.174). CONCLUSION:
      Notification regarding one's HIV seropositivity could considerably reduce the
      incidence of unsafe sexual behaviors in HIV-positive persons, however, women and
      those who were living with sexual partners seemed likely to keep practicing
      unsafe sexual behavior, thereafter.

PMID- 25975546
TI  - [Comparison between methods as polling booth survey and face-to-face interview in
      understanding the high-risk behavior among HIV-positive clients of female sex
      workers].
AB  - OBJECTIVE: Face-to-face interview (FTFI) and polling booth survey (PBS) were
      applied to compare the high risk behavior among HIV-positive clients of female
      sex workers (CFSWs). METHODS: This study was conducted in antiretroviral therapy
      (ART) out-patients centers in Hengyang city, where clients who had been informed
      on their HIV-positive status for 6 months or longer were recruited. FTFI was
      first used to tackle on 8 sensitive questions related to sexual behavior,
      followed by PBS to poke on the same questions. Results from FTFI and PBS were
      then compared. RESULTS: Compared with FIFI, results in the PBS showed higher
      proportion of participants who reported "having had history of sexually
      transmitted diseases before knowing that they were infected with HIV" (40.6% vs.
      24.2%) but lower proportions on "frequency of having sex with regular sexual
      partner less than 4 times per month" and "using condoms consistently with regular
      sexual partners in past 6 months (44.4% vs. 63.0%)". There were no significant
      differences in the remaining 5 questions shown in the results from the two
      methods. CONCLUSION: HIV-positive CFSWs continued to practice unsafe sexual
      behaviors after knowing their HIV related status. Compared with FTFI, PBS seemed
      to have revealed higher proportion of unsafe sex behaviors, so as to generated
      more reliable data. While comparing with PBS, the traditional FTFI might have
      underestimated the risk behaviors among those HIV-positive CFSWs.

PMID- 25975547
TI  - [Characteristics of co-morbid psychiatric disability and injury caused disability
      in Chinese population].
AB  - OBJECTIVE: To investigate the relations between psychiatric disability and co
      morbid disability caused by injury, severity of the disabilities, as well as the
      unmet health care need among people living with both disabilities. METHODS: Data
      collected through both the Second China National Sample Survey on Disabilities in
      2006 and the Follow-up Studies in 2009, were utilized. Sampling weights were
      considered to appropriately estimate situations in the total Chinese population.
      RESULTS: Among people with psychiatric disability, 2.7% of them were affected by
      other injury-caused disabilities as visual, hearing, speech, psychical and
      intellectual disabilities. Among people with disability that caused by injuries,
      1.8% of them were living with psychiatric disability as well. The prevalence
      rates of psychiatric disability and injury caused disability were as 0.94% and
      0.63%, respectively. More than half of the co-morbid people were living with
      profound disabilities while 46.32% of the people living with both disabilities
      developed co-morbid disabilities in the same year. Data from the follow-up
      program showed that 56.25% of the people living with co-morbid disabilities did
      not receive any psychiatric treatment which were in need. CONCLUSION: There
      seemed a close but bidirectional relationship existed between the mental
      disorders and injuries that calling for better mental health services provided
      for people with psychiatric disabilities.

PMID- 25975548
TI  - [Incidence of and related risk factors on preterm delivery among HIV-infected
      pregnant women in China].
AB  - OBJECTIVE: To measure the incidence rates of preterm delivery in HIV-infected
      pregnant women and to explore related potential risk factors. METHODS: Data from
      'Information System of Prevention of Mother-to-child Transmission of HIV
      Management in China, 2013' was used in the study. Information regarding
      demographic characteristics, pregnancy, HIV relevant situations and pregnancy
      outcomes related to these HIV-infected pregnant women, were extracted and
      analyzed. Incidence of preterm delivery was calculated with related potential
      risk factors explored. RESULTS: 3 913 HIV-infected pregnant women were involved
      in this study, including 336 of them having undergone preterm deliveries (8.6%).
      Results from univariate and multivariate analyses showed that preterm delivery
      was associated with factors as: maternal age, ethnicity, education, being
      migrant, pregnancy hypertension, multiple pregnancy and times of antenatal care
      visits (P < 0.05) of the pregnant women. Compared with those who contracted the
      HIV infection through drug injection, the ones who were infected through other
      routes suffered fewer preterm deliveries (adjusted OR = 0.562, 95% CI: 0.360
      0.879). Pregnant women who received antiretroviral therapy either between 14 to
      27 gestational weeks or during the period of less than 14, were more likely to
      experience preterm delivery, comparison to those who did not receive the therapy
      during pregnancy. The adjusted ORs were 1.712 (95% CI: 1.196-2.451) and 1.862
      (95% CI: 1.261-2.749), respectively. CONCLUSION: Preterm delivery was a common
      adverse outcome during pregnancy among HIV-infected women in China. Other than
      traditionally known risk factors, routes of transmission and the use of
      antiretroviral therapy might also be associated with the increased risks for
      preterm delivery.

PMID- 25975549
TI  - [Analysis on sports and recreation related injuries through data from the Chinese
      National Injury Surveillance System, 2009-2013].
AB  - OBJECTIVE: To understand the trend and characteristics of sports and recreation
      related injuries reported from National Injury Surveillance System (NISS) to
      provide basis for corresponding prevention strategies and decision-making.
      METHODS: Descriptive analysis was applied to display the overall trend, general
      information, injury event and clinical characteristics of sports and recreation
      related injuries from 2009 to 2013. RESULTS: The proportion of sports and
      recreation related injuries among all injuries increased from 2009 to 2013, with
      an annual increase exceeding 45% (46.21%, 47.32%, 48.14%, 52.00%, 53.65%,
      respectively). Sports and recreation related injuries mainly involved males, with
      15-29 age groups, particularly in summer and autumn. Sports and recreation
      related injuries mostly occurred at home, with annual rates of proportion as
      33.07%, 34.16%, 32.98%, 34.57 and 36.22%, mostly caused by falls (41.19%, 41.64%,
      44.70%, 47.41%, 47.96%). Contusion and abrasion were the leading types of
      injuries (43.49%, 44.56%, 45.14%, 45.02%, 45.62%) with the serious leading types
      as fracture, concussion/cerebral contusion or laceration, and sharp force
      injury/bite/open wounds. Head was the part mainly involved (31.30%, 32.48%,
      31.89%, 30.88%, 29.44%) in injuries. Most sports and recreation related injuries
      were minor and most of the patients headed home after treatment. CONCLUSION:
      Sports and recreation related injury appeared a growing public health problem in
      China. Children and the elderly should be the target groups for intervention.
      Falls prevention in sports and the use of protection gears should be the focus
      countermeasures for prevention.

PMID- 25975550
TI  - [Study on head injuries through data from the National Injury Surveillance System
      of China, 2013].
AB  - OBJECTIVE: To understand the epidemiological characteristics of head injuries
      through data from the Chinese National Injury Surveillance System (NISS).
      METHODS: Descriptive analysis was applied to display the overall trend of head
      injuries in 2013 in NISS and to depict general information, events and clinical
      characteristics of head injuries with SPSS 19.0 software. RESULTS: In 2013, 195
      189 cases of head injuries were collected, males were twice higher than females,
      with 25.19% of them under 30-44 years of age. The three leading causes
      responsible for head injuries were falls (42.17%), blunt force injuries (27.46%)
      and road traffic injury (23.33%). Main locations causing head injuries were in
      road/street (31.41%), at home (25.02%) and public places (17.17%). Recreation
      activates (54.22%), driving (19.73%), paid work (12.95%) were the three major
      activities when injuries took place. Majority of the cases belonged to
      unintentional (86.79%) with bruise injuries (65.18%). Those mild injuries
      (78.87%) were treated and discharged (82.02%). CONCLUSION: In 2013, head injuries
      were seen more in males than in females, mostly involved in labor force
      population on head injuries. The leading causes for head injuries were falls,
      blunt injuries and road traffic.

PMID- 25975551
TI  - [Epidemiological investigation on an outbreak of severe fever with
      thrombocytopenia syndrome in northwest Zhejiang province].
AB  - OBJECTIVE: To investigate the source, transmission route and risk factors of an
      outbreak of severe fever with thrombocytopenia syndrome (SFTS). METHODS: Case
      definition was made and suspected cases were searched. A standardized
      questionnaire was used to collect information on demographic features (age,
      gender, occupation, residential address), history of exposure, clinical signs and
      symptoms etc. Blood samples were collected from 12 suspected cases while index
      patient's blood samples were collected from walls of the residence. All samples
      were detected for SFTS virus using RT-PCR. Sero-prevalence rates of SFTS virus
      IgG were also conducted among healthy people, host and vectors. RESULTS: A total
      of 13 cases including 6 male and 7 female were identified during this outbreak in
      May 2014. Index patient developed illness onset on April 23 and died on May 1.
      Secondary patients would include 8 family members, 3 neighborhoods, 1 individual
      who lived in the same village, developing illness onset between May 10 and 16,
      with a peak on May 13. The incubation period was 9-15 days. Clinical signs and
      symptoms appeared as fever (100%), chill (92%), anergy (92%), body aches (92%),
      anorexia (92%), headache (77%), nausea (69%) etc. Neutropenia and
      thrombocytopenia also appeared. History of the index patient showed that she
      collected tea leaves in her hometown 1 month before the illness onset. After
      index patient died on May 1, 9 secondary patients had directly contacted the
      blood of the deceased. Data from the retrospective cohort study showed that
      'direct contact with blood' was an important risk factor (RR = 43.36, 95% CI:
      13.66-137.63, P = 0.000). CONCLUSION: Majority of the secondary patients of these
      clusters contracted the SFTS virus infection through exposure to the blood of the
      index patient. However, aerosol transmission could not be ruled out, suggesting
      that precaution should be taken for doctors, nurses and family members when
      looking after the patients with SFTS virus infection.

PMID- 25975552
TI  - [Isolation and identification of mosquito-borne arboviruses in Yuncheng city,
      Shanxi province, 2012].
AB  - OBJECTIVE: To investigate the species and distribution of mosquitoes and mosquito
      borne arboviruses in Yuncheng city of Shanxi province, China. METHODS: Mosquito
      samples were collected in 19 collection sites from Linyi county and Yongji city
      in Yuncheng city, in August, 2012. After identification and classification, all
      the specimens were homogenized and centrifuged to acquire supernatant before
      being inoculated to both C6/36 and BHK21 cells for viral isolation. Positive
      isolates were identified with arbovirus species-specific primers under RT-PCR,
      for further sequencing and phylogenetic analysis. RESULTS: A total of 10 455
      mosquitoes of 7 species in 4 genuese were collected. The predominant mosquito
      species in Linyi county was Culex pipens pallens (91.96%, 3 911/4 253), but the
      one in Yongji city was Culex tritaeniorhynchus (72.85%, 4 518/6 202). A total of
      23 strains of viruses were isolated from the mosquito pools. 15 strains from
      Culex tritaeniorhynchus and Culex pipens pallens were identified as genotype I
      Japanese encephalitis virus (JEV). Four strains from Culex pipens pallens were
      identified as Culex flavivirus (CxFV). Three strains from Culex pipens pallens
      were identified as Culex pipiens pallens densovirus (CppDNV). One strain from
      Armigeres subalbatus and Aedes albopictus was identified as Getah virus (GETV).
      CONCLUSION: Four kinds of arboviruses were isolated from the mosquito pools,
      including GETV and CxFV, which were isolated and documented in Shanxi province
      for the first time. In the city of Yuncheng, Culex tritaeniorhynchus had been the
      predominant species and major vector for transmitting JEV. Genotype I JEV
      remained the major JEV circulating in the local natural environment.

PMID- 25975553
TI  - [Study on the population-genetics of Mycobacterium tuberculosis from Sichuan
      Basin in China].
AB  - OBJECTIVE: To explore the population-genetics characteristics of Mycobacterium
      tuberculosis (MTB) prevailing at the Sichuan basin of China. METHODS: A total of
      413 MTB strains collected from Sichuan basin were genotyped by large sequence
      polymorphism (LSP) and 15 loci variable number tandem repeat (VNTR). Difference
      between the distribution of lineage population was analyzed by chi(2)-test and
      the discriminatory ability of each VNTR locus was evaluated under the Hunter
      Gaston Discriminatory Index (HGI). Both phylogeny on population level and genetic
      structure were demonstrated through N-J tree and the Minimal Spanning Tree (MST).
      Genetic differentiation of different lineage strains was analyzed by Analysis of
      Molecular Variance (AMOVA). Time of the Most Recent Common Ancestor (TMRCA) was
      calculated based on the Bayesian model. RESULTS: Four hundred and thirteen MTBs
      were divided into two major lineages, in which the Beijing lineage accounted for
      56.2% (232/413) and the Euro-American lineage for 43.8% (181/413). There was no
      significant difference of population distribution between the two lineages (P >
      0.05). The N-J tree of Beijing lineage MTB presented distinctly "star-like" and
      72.4% strains were grouped to one clonal complex in MST. The Euro-American
      lineages MTB presented "branch-like" in N-J tree and were grouped into multiple
      clonal complexes in MST. There was significant genetic differentiation in Beijing
      lineage MTBs between Chongqing and Sichuan (FST = 0.018 91, P < 0.05), but not in
      the Euro-American lineage MTB (FST = 0.005 19, P > 0.05). TMRCA of the largest
      clonal complex in Euro-American lineage MTB appeared to be 723 (95% CI: 517-946)
      years. CONCLUSION: Both Beijing lineage and Euro-American lineage MTBs were
      competitively prevalent in the Sichuan basin. There was some difference noticed
      between the two lineages referring to genetic differentiation. The invasion of
      Euro-American lineages MTB to the basin area might be associated with a war
      occurred in this area about 720 years ago.

PMID- 25975554
TI  - [Relationship between interleukin 28B, equilibrative nucleoside transporters 1
      gene polymorphisms and spontaneous clearance of HCV in HIV/HCV co-infectors].
AB  - OBJECTIVE: To explore the association between interleukin 28B (IL-28B),
      equilibrative nucleoside transporters 1 (ENT1) gene polymorphisms and spontaneous
      clearance of HCV in HIV/HCV co-infectors in Hunan province. METHODS: Genotypes of
      IL-28B and ENT1 (rs12980275, rs12979860, rs8099917 and rs760370) were analyzed in
      107 HIV/HCV co-infectors in Hunan province and the distributions of gene
      polymorphisms were compared between chronic hepatitis and spontaneous clearance
      groups. RESULTS: The major genotypes in rs12980275, rs12979860 and rs8099917 of
      IL-28B were AA, CC and TT in HIV/HCV co-infectors, which accounted for 84.1% of
      each. The three single nucleotide polymorphisms were highly linkage
      disequilibrium (r2 > 0.94) and the differences of genotype distribution were
      statistically significant between chronic hepatitis and the spontaneous clearance
      groups (P < 0.05). Infectors which carrying the major genotypes were more
      susceptible to spontaneous clearance of HCV. Differences of the genotype
      distributions in rs760370 of ENT1 were not statistically significant between the
      two groups. CONCLUSION: Genotypes AA, CC and TT of IL-28B were related to
      spontaneous clearance of HCV in HIV/HCV co-infectors.

PMID- 25975555
TI  - [Epidemiological and clinical features of norovirus infection among diarrhea
      patients from the enteric clinics in Beijing, 2013-2014].
AB  - OBJECTIVE: To investigate the epidemiological and clinical characteristics of
      norovirus infection on diarrhea patients from the enteric clinics in Beijing.
      METHODS: From April 2013 to March 2014, 1 892 fecal specimens and related
      epidemiological information were collected among diarrhea patients visiting the
      enteric clinics in Beijing. Norovirus was detected by real time RT-PCR, and data
      was analyzed under the descriptive epidemiological method. RESULTS: A total of
      269 positive cases were found among 1 892 diarrhea patients, with a positive rate
      as 14.2%. Norovirus caused diarrhea mainly occurred in seasons with lower
      temperature. Higher positive rates of norovirus were found in northwest
      mountainous area. Norovirus diarrhea was more commonly seen in children between 6
      month and 5 years old, with differences between the two groups statistically
      significant (P = 0.006). Compared with other occupation, a higher infection rate
      was identified in children, with differences between the two groups statistically
      significant (P = 0.025). Nausea and vomiting appeared more common in diarrhea
      patients with norovirus infection, with differences between the two groups
      statistically significant (P < 0.05). CONCLUSION: Norovirus was an important
      pathogen which causing diarrhea in patients visiting the enteric clinics in
      Beijing. The virus was seen more in patients aged between 6 months and 5 years
      old. Nausea and vomiting were the common symptoms seen in patients with norovirus
      diarrhea.

PMID- 25975556
TI  - [Interaction between folate deficiency and aberrant expression related to fragile
      histidine triad gene in the progression of cervical cancerization].
AB  - OBJECTIVE: To explore the interaction between folate deficiency and aberrant
      expression related to fragile histidine triad (FHIT) gene in the progression of
      cervical cancerization. METHODS: A total number of 80 patients with histological
      diagnosis of cervix inflammation (CI), 55 cervical intraepithelial neoplasm I
      (CIN I), 55 cervical intraepithelial neoplasm II/III (CIN II/III) and 64 cervical
      squamous cell carcinoma (SCC) were included in this study. Levels of serum folate
      were detected by microbiological assay method and the methylation status of FHIT
      gene CpG islands was tested by methylation-specific PCR (MSP). FHIT protein
      levels were measured by Western blot. In vitro, cervical cancer cell lines CaSki
      (HPV16-positive) was treated with different concentrations of folate.
      Proliferation and apoptosis of cells, methylation of FHIT gene and the levels of
      FHIT protein expression were measured in each group. All analyses were performed
      with SPSS (version 17.0) statistical software. Differences among groups were
      assessed by chi-square test, Kruskal-Wallis test. Spearman correlation, and the
      interaction effects were evaluated by additive model. RESULTS: The levels of
      serum folate (H = 59.08, P < 0.001) and FHIT protein expression (H = 50.93, P <
      0.001) decreased gradually along with the severity of cervix lesions, while the
      methylation rates of FHIT gene CpG islands increased (trend chi2 = 28.34, P <
      0.001). Both levels of serum folate levels and FHIT protein expression were
      positively correlated (r = 0.213, P = 0.001), with an additive interaction seen
      between them in CIN I, CIN II/III, SCC groups. In vitro, both rates related to
      proliferation inhibition (r = 0.98, P < 0.001) and apoptosis (r = 0.99, P <
      0.001) together with the levels of FHIT protein expression (r = 0.97, P < 0.001)
      were all increased gradually with the increase of folate concentration while the
      methylation status of FHIT gene CpG islands all changed from positive to negative
      gradually. CONCLUSION: Results from our study revealed that both folate
      deficiency and FHIT protein aberrant low expression might increase the risk of
      developing cervical cancer and cervix precancerous lesions, and thus play a
      synergistic action in the progression of cervical cancerization.

PMID- 25975557
TI  - [Association between CYP1A1 genetic polymorphisms and coronary artery disease in
      Uygur population in Xinjiang, China].
AB  - OBJECTIVE: To assess the association between human CYP1A1 gene polymorphisms and
      coronary artery disease (CAD) among the Uygur population of China. METHODS:
      Genotypes of CYP1A1 single nucleotide polymorphisms (SNPs: rs4886605, rs12441817,
      rs4646422 and rs1048943) were detected by real-time PCR in 293 CAD patients and
      408 controls. RESULTS: Among the Uygur group, distribution of genotypes and
      allele of rs4886605 were both significantly different between CAD and the
      controls (all P < 0.05). The dominant model (CC vs. CT+TT) of rs4886605 was
      significantly lower among CAD patients than in controls. Significant differences
      were retained after the adjustment was made in all the participants (OR = 0.368,
      95% CI: 0.185-0.530, P = 0.018) and in men (OR = 0.350, 95% CI: 0.235-0.568, P =
      0.015). Distributions of genotypes and allele of rs12441817 were both
      significantly different between CAD and the controls (all P < 0.05). The dominant
      model (TT vs. CT+CC) of rs12441817 was significantly lower among patients CAD
      than in controls. Significant difference were retained after the adjustment was
      made, in total participants (OR = 0.253, 95% CI: 0.231-0.546, P = 0.016) and in
      men (OR = 0.241, 95% CI: 0.132-0.478, P = 0.002). CONCLUSION: Both rs4886605 and
      rs12441817 SNPs of the CYP1A1 gene were associated with CAD in the Uygur
      population of China.

PMID- 25975559
TI  - [The value of twin study in epigenetic research].

PMID- 25975558
TI  - [Effect of Zhenggan Tang decoction on the serum levels of leptin, adiponectin and
      insulin resistance on HBV-induced cirrhotic patients].
AB  - OBJECTIVE: To evaluate the effect of Zhenggan Tang decoction on serum levels of
      leptin, adiponectin and insulin resistance on liver cirrhosis induced by chronic
      hepatitis B. METHODS: Sixty-six patients were recruited and randomly assigned
      either to a control group or to an intervention group, with 35 cases in the
      treatment and 31 in the control group respectively. Patients in the control group
      received inosine tablets and vitamin C treatment while patients in the treatment
      group were given Zhenggan Tang decoction additionally. After 3 months of
      treatment, the serum levels of leptin and adiponectin were detected and the index
      of insulin resistance calculated. RESULTS: There were no significant difference
      between the serum levels of leptin, adiponectin and the index of insulin
      resistance seen in the control group before and after the treatment. Serum levels
      of leptin and adiponectin and the index of insulin resistance in treatment group
      were reduced significantly after the treatment (P < 0.05). There were significant
      difference in the serum levels of leptin and adiponectin between treat group and
      control group (P < 0.05). CONCLUSION: Zhenggan Tang decoction seemed to have
      reduced the serum levels of leptin, adiponectin and the index of insulin
      resistance among cirrhotic patients that induced by chronic hepatitis B.

PMID- 25975560
TI  - [Research progress on elder self-neglection].

PMID- 25975561
TI  - Role of ortho-retronasal olfaction in mammalian cortical evolution.
AB  - Fossils of mammals and their extinct relatives among cynodonts give evidence of
      correlated transformations affecting olfaction as well as mastication, head
      movement, and ventilation, and suggest evolutionary coupling of these seemingly
      separate anatomical regions into a larger integrated system of ortho-retronasal
      olfaction. Evidence from paleontology and physiology suggests that ortho
      retronasal olfaction played a critical role at three stages of mammalian cortical
      evolution: early mammalian brain development was driven in part by ortho
      retronasal olfaction; the bauplan for neocortex had higher-level association
      functions derived from olfactory cortex; and human cortical evolution was
      enhanced by ortho-retronasal smell.

PMID- 25975563
TI  - The impact of thyroid function and thyroid autoimmunity on embryo quality in
      women with low functional ovarian reserve: a case-control study.
AB  - BACKGROUND: Women with hyper-and hypothyroidism are at increased risk for
      infertility and adverse pregnancy outcomes. Whether in women considered euthyroid
      thyroid function (TSH values) and thyroid autoimmunity (thyroid antibodies)
      influence in vitro fertilization (IVF) cycle outcome has, however, remained
      controversial. Any such effect should be easily visible in women with low
      functional ovarian reserve (LFOR) and thus small oocyte and embryo numbers.
      METHODS: We evaluated the relationship between TSH levels and embryo quality in
      euthyroid women with LFOR undergoing IVF. Mean age for the study population was
      39.9+/-4.6 years. Embryo quality was assessed in 431 embryos from 98 first IVF
      cycles according to TSH levels (with cut-off 2.5MUIU/mL), and to presence versus
      absence of thyroid autoantibodies. RESULTS: Mean Anti Mullerian hormone (AMH) was
      0.8+/-0.8 ng/mL and mean TSH was 1.8+/-0.9 MUIU/mL. Comparable embryo quality was
      observed in women with TSH<= and >2.5MUIU/mL. TPO antibodies significantly
      affected embryo quality in women with low-normal TSH levels (P=0.045). In women
      with high-normal TSH levels, increasing TSH had a negative impact on embryo
      quality (P=0.027). A trend towards impaired embryo quality with TPO antibodies
      was also observed in these patients (p=0.057). CONCLUSIONS: TPO antibodies affect
      embryo quality in euthyroid women with low-normal TSH<=2.5 MUIU/mL. In women with
      high-normal TSH levels, increasing TSH levels, and possibly TPO antibodies,
      appear to impair embryo quality. These results suggest that the negative impact
      of thyroid autoimmunity becomes apparent, once thyroid hormone function is
      optimized.

PMID- 25975562
TI  - Subclassification of prostate cancer circulating tumor cells by nuclear size
      reveals very small nuclear circulating tumor cells in patients with visceral
      metastases.
AB  - BACKGROUND: Although enumeration of circulating tumor cells (CTCs) has shown some
      clinical value, the pool of CTCs contains a mixture of cells that contains
      additional information that can be extracted. The authors subclassified CTCs by
      shape features focusing on nuclear size and related this with clinical
      information. METHODS: A total of 148 blood samples were obtained from 57 patients
      with prostate cancer across the spectrum of metastatic states: no metastasis,
      nonvisceral metastasis, and visceral metastasis. CTCs captured and enumerated on
      NanoVelcro Chips (CytoLumina, Los Angeles, Calif) were subjected to pathologic
      review including nuclear size. The distribution of nuclear size was analyzed
      using a Gaussian mixture model. Correlations were made between CTC subpopulations
      and metastatic status. RESULTS: Statistical modeling of nuclear size distribution
      revealed 3 distinct subpopulations: large nuclear CTCs, small nuclear CTCs, and
      very small nuclear CTCs (vsnCTCs). Small nuclear CTCs and vsnCTC identified those
      patients with metastatic disease. However, vsnCTC counts alone were found to be
      elevated in patients with visceral metastases when compared with those without
      (0.36 +/- 0.69 vs 1.95 +/- 3.77 cells/mL blood; P<.001). Serial enumeration
      studies suggested the emergence of vsnCTCs occurred before the detection of
      visceral metastases. CONCLUSIONS: There are morphologic subsets of CTCs that can
      be identified by fundamental pathologic approaches, such as nuclear size
      measurement. The results of this observational study strongly suggest that CTCs
      contain relevant information regarding disease status. In particular, the
      detection of vsnCTCs was found to be correlated with the presence of visceral
      metastases and should be formally explored as a putative blood-borne biomarker to
      identify patients at risk of developing this clinical evolution of prostate
      cancer.

PMID- 25975564
TI  - Copper-catalyzed reactions: Research in the gas phase.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is becoming an important tool
      for mechanistic studies in organic and organometallic chemistry. It allows
      investigation of reaction mixtures including monitoring of reactants, products,
      and intermediates, studying properties of the intermediates and their reactivity.
      Studying the reactive species in the gas phase can be advantageously combined
      with theoretical calculations. This review is focused on ESI-MS studies of copper
      catalyzed reactions. Possible effects of the electrospray process on the transfer
      of the copper complexes to the gas phase are discussed. The plethora of mass
      spectrometric approaches is demonstrated on copper mediated C-H activations,
      cross coupling reactions, rearrangements, organocuprate chemistry, and other
      examples.

PMID- 25975565
TI  - Genomic and experimental evidence for multiple metabolic functions in the
      RidA/YjgF/YER057c/UK114 (Rid) protein family.
AB  - BACKGROUND: It is now recognized that enzymatic or chemical side-reactions can
      convert normal metabolites to useless or toxic ones and that a suite of enzymes
      exists to mitigate such metabolite damage. Examples are the reactive
      imine/enamine intermediates produced by threonine dehydratase, which damage the
      pyridoxal 5'-phosphate cofactor of various enzymes causing inactivation. This
      damage is pre-empted by RidA proteins, which hydrolyze the imines before they do
      harm. RidA proteins belong to the YjgF/YER057c/UK114 family (here renamed the Rid
      family). Most other members of this diverse and ubiquitous family lack defined
      functions. RESULTS: Phylogenetic analysis divided the Rid family into a widely
      distributed, apparently archetypal RidA subfamily and seven other subfamilies
      (Rid1 to Rid7) that are largely confined to bacteria and often co-occur in the
      same organism with RidA and each other. The Rid1 to Rid3 subfamilies, but not the
      Rid4 to Rid7 subfamilies, have a conserved arginine residue that, in RidA
      proteins, is essential for imine-hydrolyzing activity. Analysis of the
      chromosomal context of bacterial RidA genes revealed clustering with genes for
      threonine dehydratase and other pyridoxal 5'-phosphate-dependent enzymes, which
      fits with the known RidA imine hydrolase activity. Clustering was also evident
      between Rid family genes and genes specifying FAD-dependent amine oxidases or
      enzymes of carbamoyl phosphate metabolism. Biochemical assays showed that
      Salmonella enterica RidA and Rid2, but not Rid7, can hydrolyze imines generated
      by amino acid oxidase. Genetic tests indicated that carbamoyl phosphate
      overproduction is toxic to S. enterica cells lacking RidA, and metabolomic
      profiling of Rid knockout strains showed ten-fold accumulation of the carbamoyl
      phosphate-related metabolite dihydroorotate. CONCLUSIONS: Like the archetypal
      RidA subfamily, the Rid2, and probably the Rid1 and Rid3 subfamilies, have imine
      hydrolyzing activity and can pre-empt damage from imines formed by amine oxidases
      as well as by pyridoxal 5'-phosphate enzymes. The RidA subfamily has an
      additional damage pre-emption role in carbamoyl phosphate metabolism that has yet
      to be biochemically defined. Finally, the Rid4 to Rid7 subfamilies appear not to
      hydrolyze imines and thus remain mysterious.

PMID- 25975566
TI  - Early detection of breast cancer using total biochemical analysis of peripheral
      blood components: a preliminary study.
AB  - BACKGROUND: Most of the blood tests aiming for breast cancer screening rely on
      quantification of a single or few biomarkers. The aim of this study was to
      evaluate the feasibility of detecting breast cancer by analyzing the total
      biochemical composition of plasma as well as peripheral blood mononuclear cells
      (PBMCs) using infrared spectroscopy. METHODS: Blood was collected from 29
      patients with confirmed breast cancer and 30 controls with benign or no breast
      tumors, undergoing screening for breast cancer. PBMCs and plasma were isolated
      and dried on a zinc selenide slide and measured under a Fourier transform
      infrared (FTIR) microscope to obtain their infrared absorption spectra.
      Differences in the spectra of PBMCs and plasma between the groups were analyzed
      as well as the specific influence of the relevant pathological characteristics of
      the cancer patients. RESULTS: Several bands in the FTIR spectra of both blood
      components significantly distinguished patients with and without cancer.
      Employing feature extraction with quadratic discriminant analysis, a sensitivity
      of ~90 % and a specificity of ~80 % for breast cancer detection was achieved.
      These results were confirmed by Monte Carlo cross-validation. Further analysis of
      the cancer group revealed an influence of several clinical parameters, such as
      the involvement of lymph nodes, on the infrared spectra, with each blood
      component affected by different parameters. CONCLUSION: The present preliminary
      study suggests that FTIR spectroscopy of PBMCs and plasma is a potentially
      feasible and efficient tool for the early detection of breast neoplasms. An
      important application of our study is the distinction between benign lesions
      (considered as part of the non-cancer group) and malignant tumors thus reducing
      false positive results at screening. Furthermore, the correlation of specific
      spectral changes with clinical parameters of cancer patients indicates for
      possible contribution to diagnosis and prognosis.

PMID- 25975567
TI  - GAMPMS: Genetic algorithm managed peptide mutant screening.
AB  - The prominence of endogenous peptide ligands targeted to receptors makes peptides
      with the desired binding activity good molecular scaffolds for drug development.
      Minor modifications to a peptide's primary sequence can significantly alter its
      binding properties with a receptor, and screening collections of peptide mutants
      is a useful technique for probing the receptor-ligand binding domain.
      Unfortunately, the combinatorial growth of such collections can limit the number
      of mutations which can be explored using structure-based molecular docking
      techniques. Genetic algorithm managed peptide mutant screening (GAMPMS) uses a
      genetic algorithm to conduct a heuristic search of the peptide's mutation space
      for peptides with optimal binding activity, significantly reducing the
      computational requirements of the virtual screening. The GAMPMS procedure was
      implemented and used to explore the binding domain of the nicotinic acetylcholine
      receptor (nAChR) alpha3beta2-isoform with a library of 64,000 alpha-conotoxin
      (alpha-CTx) MII peptide mutants. To assess GAMPMS's performance, it was compared
      with a virtual screening procedure that used AutoDock to predict the binding
      affinity of each of the alpha-CTx MII peptide mutants with the alpha3beta2-nAChR.
      The GAMPMS implementation performed AutoDock simulations for as few as 1140 of
      the 64,000 alpha-CTx MII peptide mutants and could consistently identify a set of
      10 peptides with an aggregated binding energy that was at least 98% of the
      aggregated binding energy of the 10 top peptides from the exhaustive AutoDock
      screening.

PMID- 25975568
TI  - Unexpected stimulation of soil methane uptake as emergent property of
      agricultural soils following bio-based residue application.
AB  - Intensification of agriculture to meet the global food, feed, and bioenergy
      demand entail increasing re-investment of carbon compounds (residues) into agro
      systems to prevent decline of soil quality and fertility. However, agricultural
      intensification decreases soil methane uptake, reducing, and even causing the
      loss of the methane sink function. In contrast to wetland agricultural soils
      (rice paddies), the methanotrophic potential in well-aerated agricultural soils
      have received little attention, presumably due to the anticipated low or
      negligible methane uptake capacity in these soils. Consequently, a detailed study
      verifying or refuting this assumption is still lacking. Exemplifying a typical
      agricultural practice, we determined the impact of bio-based residue application
      on soil methane flux, and determined the methanotrophic potential, including a
      qualitative (diagnostic microarray) and quantitative (group-specific qPCR assays)
      analysis of the methanotrophic community after residue amendments over 2 months.
      Unexpectedly, after amendments with specific residues, we detected a significant
      transient stimulation of methane uptake confirmed by both the methane flux
      measurements and methane oxidation assay. This stimulation was apparently a
      result of induced cell-specific activity, rather than growth of the methanotroph
      population. Although transient, the heightened methane uptake offsets up to 16%
      of total gaseous CO2 emitted during the incubation. The methanotrophic community,
      predominantly comprised of Methylosinus may facilitate methane oxidation in the
      agricultural soils. While agricultural soils are generally regarded as a net
      methane source or a relatively weak methane sink, our results show that methane
      oxidation rate can be stimulated, leading to higher soil methane uptake. Hence,
      even if agriculture exerts an adverse impact on soil methane uptake, implementing
      carefully designed management strategies (e.g. repeated application of specific
      residues) may compensate for the loss of the methane sink function following land
      use change. 

PMID- 25975569
TI  - Exodus of clinical pharmacologists and pharmacometricians from academia--Who is
      to blame? A policy statement from the American College of Clinical Pharmacology.

PMID- 25975570
TI  - Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony
      Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury
      in Mice.
AB  - Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem
      cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal
      transplantation of PBSCs mobilized by G-CSF could promote functional recovery
      after spinal cord injury. Spinal cords of adult nonobese diabetes/severe
      immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn).
      One week after the injury, 3.0 ul of G-CSF-mobilized human mononuclear cells
      (MNCs; 0.5 * 10(5)/ul), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 *
      10(5)/ul), or normal saline was injected to the lesion epicenter. We performed
      immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The
      number of transplanted human cells decreased according to the time course. The
      CD31-positive area was significantly larger in the MNC and CD34 groups compared
      with the vehicle group. The number of serotonin-positive fibers was significantly
      larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry
      revealed that the number of apoptotic oligodendrocytes was significantly smaller
      in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34
      transplanted mice were smaller than that in the vehicle group, indicating that
      cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both
      the MNC and CD34 groups showed significantly better hindlimb functional recovery
      compared with the vehicle group. There was no significant difference between the
      two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized
      MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber
      regeneration/sparing, and preservation of myelin, resulting in improved hindlimb
      function after spinal cord injury in comparison with vehicle-treated control
      mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of
      spinal cord injury in the ethical and immunological viewpoints, although further
      exploration is needed to move forward to clinical application. 

PMID- 25975571
TI  - Detection of Adulterants and Contaminants in Liquid Foods-A Review.
AB  - Milk and fruit juices have paramount importance in human diet. Increasing demand
      of these liquid foods has made them vulnerable to economic adulteration during
      processing and in supply chain. Adulterants are difficult to detect by consumers
      and thus necessitating the requirement of rapid, accurate and sensitive
      detection. The potential adulterants in milk and fruit juices and their limits
      set by different regulatory bodies have been briefly described in this review.
      Potential advantages and limitations of various techniques such as
      physicochemical methods, chromatography, immunoassays, molecular, electrical,
      spectroscopy with chemometrics, electronic nose, and biosensors have been
      described. Spectroscopy in combination with chemometrics has shown potential for
      rapid, precise, and sensitive detection of potential adulterants in these liquid
      foods. 

PMID- 25975572
TI  - When the going gets tough, the differentiated keep going: cybernetic self
      determination, daily obstacles, and persistent goal pursuit.
AB  - Cybernetic theories of self-regulation contend that an individual's goal system
      may work best to the extent it is differentiated. The present investigation
      pioneered an assessment of goal differentiation in relation to an important
      feature of goals--intrinsic motivation--and quantified the extent to which
      intrinsic motivation systematically increased from low- to mid- to high-level
      goals, the resulting individual difference termed cybernetic self-determination.
      In Study 1 (n = 106), it was found that frustrating daily events precipitated
      motivations to quit at low, but not high, levels of cybernetic self
      determination. In Study 2 (n = 111), it was found that negative feedback was
      associated with reduced goal persistence at low, but not high, levels of
      cybernetic self-determination. The findings therefore converge on the idea that
      individual differences in cybernetic self-determination are consequential in
      buffering reactions to obstacles in daily life. Implications for personality,
      motivation, and self-regulation literatures are discussed.

PMID- 25975573
TI  - Self-talk: conversation with oneself? On the types of internal interlocutors.
AB  - The two studies presented in the article aimed to empirically verify the
      tentative typology of internal interlocutors in self-talk proposed in a previous
      research project. The typology comprised four emotional types: Faithful Friend,
      Ambivalent Parent, Proud Rival, and Helpless Child. Study 1 involved 98
      participants (49 women) and Study 2 involved 114 (55 women), mostly students. In
      both studies, the names of internal interlocutors were generated by participants
      as qualitative data, quantified by reference to the standard set of affect terms,
      and, as affective patterns, subjected to clustering. Study 2 fully confirmed the
      recent results, whereas Study 1 revealed a new interlocutor type instead of
      Helpless Child - Calm Optimist. The conducted studies confirm the existence of
      four main types of inner interlocutors and provide a reason to verify the
      existence of Calm Optimist. 

PMID- 25975574
TI  - Parental support and adolescent motivation for dieting: the Self-Determination
      Theory perspective.
AB  - This article focuses on parents' role in overweight adolescents' motivation to
      diet and successful weight loss. The study employed Self-Determination Theory
      (SDT) as the theoretical framework (Deci & Ryan, 2000, 2011). Ninety-nine
      participants (ages 20-30) who had been overweight during adolescence according to
      their Body Mass Index (BMI mean = 25, SD = 1.6), completed retrospective
      questionnaires about their motivation to diet and their parents' behavior in the
      context of dieting. Findings from a structural equation modeling analysis
      suggested that participants who viewed their parents' as more need-supportive
      demonstrated more autonomous motivation to diet, which, in turn, contributed to
      their successful weight loss. The findings highlight the importance of parental
      support of adolescents' psychological needs in the quality of their motivation to
      diet. This is an important insight for parents and professionals who aim to
      encourage more constructive parent involvement in adolescents' dieting and well
      being. 

PMID- 25975575
TI  - The association between psychological well-being and problematic use of Internet
      communicative services among young people.
AB  - Previous studies on problematic Internet use have focused almost exclusively on
      the fact that presence of negative functioning, such as social anxiety,
      depressive symptoms, or loneliness, represents a risk factor for unhealthy use of
      the web. For this reason the aim of the present study was to investigate the
      association between psychological well-being dimensions and problematic use of
      Internet communicative services. In the current study 495 undergraduate students
      were recruited. The Italian adaptations of the Psychological Well-being Scales
      and the Generalized Problematic Internet Use Scale 2 (GPIUS2) were used to assess
      psychological well-being dimensions and generalized problematic Internet use,
      respectively. Psychological well-being dimensions explained a significant portion
      of variance for the GPIUS2 total score levels, after controlling for sex, age,
      and occupational status. The levels of Autonomy, Environmental Mastery, and
      Positive Relations with Others acted as significant negative predictors of the
      tendency to use the web for regulating negative feelings, compulsive use of the
      web, and the negative outcomes that can arise as a result. The overall findings
      of the present study provide preliminary evidence that low psychological well
      being is associated with problematic use of Internet communicative services. 

PMID- 25975576
TI  - The effects of dysphoria and personality on negative self-referent attitudes and
      perceptions of the attitudes of others.
AB  - The cognitive model of depression posits that depressed individuals harbor more
      dysfunctional self-referent attitudes, but little is known about how depressed
      individuals perceive the attitudes and perceptions of others in their social
      arena. This study examined whether dysphoric individuals perceive others to hold
      equally negative attitudes about themselves, and whether such perceptions depend
      on sociotropic (i.e., highly invested in social approval and relationship
      success) and autonomous (i.e., highly invested in vocational or academic
      achievement and goal attainment) personality styles. A sample of undergraduate
      students (N = 197) was recruited, and after the assessment of their depression
      symptoms and personality style, participants read vignettes that described
      negative scenarios, and imagined that these scenarios occurred to themselves or
      the general university student. After reading each vignette, participants also
      rated their agreement with a number of statements that assessed dysfunctional
      attitudes. Results indicated that elevated dysphoria (i.e., showing signs of
      depression) scores were positively associated with dysfunctional self-referent
      attitudes. Further, moderational analyses examining the interaction of sociotropy
      and dysphoria did not support the hypothesis that individuals higher on dysphoria
      and sociotropy were less likely to perceive others as harboring negative
      attitudes about themselves in comparison to those with elevated dysphoria and
      lower levels of sociotropy. Last, individuals showing elevated dysphoria and
      higher scores on subdomains of autonomy were more likely to perceive others as
      exhibiting negative attitudes about themselves than those with low levels of the
      trait. These findings, their implications, and strengths and limitations of the
      current investigation are further discussed. 

PMID- 25975577
TI  - Subjective cues to deception/honesty in a high stakes situation: an exploratory
      approach.
AB  - The low ecological validity of much of the research on deception detection is a
      limitation recognized by researchers in the field. Consequently, the present
      studies investigated subjective cues to deception using the real life, high
      stakes situation of people making public appeals for help with missing or
      murdered relatives. It was expected that cues related to affect would be
      particularly salient in this context. Study 1 was a qualitative investigation
      identifying cues to deception reportedly used by people accurate at detecting
      deception. Studies 2 and 3 were then empirical investigations that mainly
      employed the cues reported in Study 1. A number of subjective cues were found to
      discriminate between honest and deceptive appeals, including some previously
      unidentified cues, and cues likely to be context-specific. Most could be
      categorized under the themes of authenticity of emotion, and negative and
      positive affective reactions to the appealer. It is concluded that some cues to
      deception may emerge only in real life, high stakes situations; however, it is
      argued that some of these may be influenced by observers' perceptions of the
      characteristics of offenders, rather than acts of deception per se. 

PMID- 25975579
TI  - Osthole promotes anti-tumor immune responses in tumor-bearing mice with
      hepatocellular carcinoma.
AB  - Osthole, a natural coumarin derivative, has been shown to have anti-tumor and
      anti-inflammatory activity. However, the effect of osthole on anti-tumor immune
      responses in tumor-bearing mice has not yet been reported. In the present study,
      osthole treatment did not affect the weight and the coefficient of thymus and
      spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However,
      osthole administration significantly elevated the proportion and number of the
      splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor
      tissues, and the levels of IL-2 and TNF-alpha in the serum of HCC tumor-bearing
      mice. Our results suggested that osthole could promote the activation of the
      tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of
      CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly
      decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the
      spleen. Taken together, osthole could enhance the T cell mediated anti-tumor
      immune responses in the tumor-bearing mice with HCC.

PMID- 25975578
TI  - The RET fusion gene and its correlation with demographic and clinicopathological
      features of non-small cell lung cancer: a meta-analysis.
AB  - PURPOSE: The RET fusion gene is a novel oncogene observed in a subset of NSCLC in
      recent years. Nevertheless, the results of epidemiological studies concerning the
      gene remain unclear. Thus, a meta-analysis was conducted to evaluate the
      correlation of RET fusion gene with demographic and clinicopathological features
      of NSCLC. METHODS: PubMed, Embase, and Web of Science databases were searched to
      identify eligible studies. The association of RET fusion gene occurrence with
      gender, age, smoking status, histology type and tumor stage were analyzed in meta
      analysis. Subgroup analysis according to patients' location (Asian and non-Asian)
      was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were
      calculated to assess the correlation. RESULTS: Nine studies with a total of 6,899
      NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion
      gene were detected. The RET fusion gene was identified at significantly higher
      frequencies in female (OR = 0.55, 95%CI = 0.35-0.85) than male patients and in
      young (<60) patients (OR = 0.43, 95%CI = 0.19-0.99) than old patients (<=60),
      particularly in patients from Asian. A significant higher frequency was also
      identified in non-smokers (OR = 0.28, 95% CI = 0.16-0.49), and in patients with
      lung adenocarcinomas (OR = 3.59, 95%CI = 1.50-8.56). Additionally, no association
      between RET fusion gene and the TNM stage of tumor was observed. CONCLUSION: RET
      fusion gene occurred predominantly in Asian females with younger age, in non
      smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients
      might be good candidates for personalized diagnostic and therapeutic approaches.

PMID- 25975580
TI  - Immunomodulatory effects of the pentapeptide YGSRS on human peripheral-blood
      mononuclear cells.
AB  - CONTEXT: The pentapeptide YGSRS is originated from coffee bean, while its
      pharmacological features have little been examined. OBJECTIVES: We investigated
      the effects of YGSRS on proliferation, cytokine production and CD4+ CD25+ Foxp3+
      regulatory T (Treg) cell frequency of human peripheral blood mononuclear cells
      (PBMCs) activated by T-cell mitogen. MATERIALS AND METHODS: The effects of YGSRS
      on T-cell mitogen-activated PBMCs were assessed by WST assay procedures.
      Concentrations of Th1/Th2/Th17 cytokines in the PBMCs culture medium were
      analyzed with beads-array procedures followed by analysis with flow cytometry.
      The CD4+ CD25+ Foxp3+ Treg cells in mitogen-activated PBMCs were stained with
      fluorescence-labeled specific antibodies followed by flow cytometry. RESULTS:
      YGSRS at 1-10,000 ng/ml (1.56-15,600 nM) has a tendency to promote the mitogen
      activated proliferation of PBMCs, but the effects were not statistically
      significant. YGSRS affect the production of tumor necrosis factor (TNF) alpha,
      interleukin (IL)-4, IL-6 and IL-10 from the activated PBMCs, and statistically
      significant increase in the concentrations of IL-6 and IL-10 in the medium were
      observed at 1-1000 ng/ml (1.56-1560 nM) (p < 0.05). YGSRS has a tendency to
      decrease the frequency of Treg cells in the activated PBMCs, but the difference
      was not statistically significant. DISCUSSION AND CONCLUSIONS: The data suggest
      that the pentapeptide YGSRS affects the production of several types of cytokines
      from activated human peripheral T cells, which may modulate Th2 type immunity.

PMID- 25975581
TI  - Anti-inflammatory effects of isoacteoside from Abeliophyllum distichum.
AB  - Isoacteoside, a dihydroxypheynylethyl glycoside, is a major bioactive component
      of Abeliophyllum distichum (White Forsythia) which is a deciduous shrub native to
      the south and central areas of Korea. The present study is designed to evaluate
      the anti-inflammatory activities and underlying mechanisms of isoacteoside in
      human mast cell line, HMC-1 cells. We isolated isoacteoside from A. distichum.
      The anti-inflammatory effect of isoacteoside was investigated in HMC-1 cells by
      studying the following markers: phorbol 12-myristate 13-acetate and calcium
      ionophore A23187 (PMACI)-induced interleukin (IL)-1beta, IL-6, IL-8, and tumor
      necrosis factor alpha (TNF-alpha) secretion and mRNA expression by ELISA and RT
      PCR, respectively. In addition, mechanism related to anti-inflammatory was
      investigated by Western blotting. Isoacteoside significantly suppressed the
      production and mRNA expression of proinflammatory cytokines including IL-1beta,
      IL-6, IL-8 and TNF-alpha in PMACI-stimulated HMC-1 cells without cytotoxicity. It
      was found that anti-inflammatory effects of isoacteoside are mediated by action
      on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38,
      extracellular signal-regulated protein kinase) and nuclear factor-kappa B
      pathways. Taken together, the present findings provide new insights that
      isoacteoside may be a promising anti-inflammatory agent for inflammatory
      disorders. 

PMID- 25975582
TI  - Therapeutic effects of dasatinib in mouse model of multiple sclerosis.
AB  - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for
      multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune
      responses that lead to an inflammatory demyelination and axonal damage. Dasatinib
      (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory
      properties that abrogates multiple signal transduction pathways in immune cells.
      In the present research, our aim was to test the therapeutic efficacy of
      dasatinib in experimental model of MS. METHODS: We performed EAE induction in
      female C57BL/6 mice by myelin oligodendrocyte glycoprotein(35-55) (MOG(35-55)) in
      Complete Freund's Adjuvant (CFA) emulsion, and used dasatinib for the treatment
      of EAE. During the course of study, clinical evaluation was assessed, and on day
      21 post-immunization blood samples were taken from the heart of mice for tumor
      necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and antioxidants capacity
      evaluation. The mice were sacrificed and brains and cerebellums of mice were
      removed for histological analysis. Also for in vitro analysis, we used C6
      astrocytoma cell line to evaluate the inhibitory effects of dasatinib in cell
      proliferation and matrix metalloproteinase-2 (MMP-2) activity. RESULTS: Our
      findings demonstrated that dasatinib had beneficial effects on EAE by lower
      incidence, attenuation in the severity and a delay in the onset of disease. The
      serum level of NO and TNF-alpha in dasatinib treated mice was significantly lower
      than control mice. In vitro, dasatinib inhibited cell proliferation and MMP-2
      activity. CONCLUSION: Dasatinib with its potential therapeutic effects and
      immunomodulatory properties may be recommended, after additional necessary tests
      and trials, for the treatment of MS.

PMID- 25975583
TI  - Enzymatic kinetic resolution of internal propargylic diols. Part I: a new
      approach for the synthesis of (S)-pent-2-yn-1,4-diol, a natural product from
      Clitocybe catinus.
AB  - Internal bis-substituted propargylic diols were subjected to enzymatic kinetic
      resolution promoted by CAL-B. Employing a two round sequence EKR, mono- and bis
      acetoxy propargylic products were obtained in a high enantiomeric ratio (E >
      200). The efficiently resolved chiral 8b was applied in a concise synthesis of
      (S)-1b, an optically active natural product produced by fungi Clitocybe catinus. 

PMID- 25975584
TI  - Excited state dynamics of thiophene and bithiophene: new insights into
      theoretically challenging systems.
AB  - The computational elucidation and proper description of the ultrafast
      deactivation mechanisms of simple organic electronic units, such as thiophene and
      its oligomers, is as challenging as it is contentious. A comprehensive excited
      state dynamics analysis of these systems utilizing reliable electronic structure
      approaches is currently lacking, with earlier pictures of the photochemistry of
      these systems being conceived based upon high-level static computations or lower
      level dynamic trajectories. Here a detailed surface hopping molecular dynamics of
      thiophene and bithiophene using the algebraic diagrammatic construction to second
      order (ADC(2)) method is presented. Our findings illustrate that ring puckering
      plays an important role in thiophene photochemistry and that the photostability
      increases when going upon dimerization into bithiophene. 

PMID- 25975585
TI  - Development of a bone targeted thermosensitive liposomal doxorubicin formulation
      based on a bisphosphonate modified non-ionic surfactant.
AB  - Bone is among the most common sites of metastasis in cancer patients, so it is an
      urgent need to develop drug delivery systems targeting tumor bone metastasis with
      the feature of controlled release. This study aimed to delivery of
      thermosensitive liposomal doxorubicin to bone for tumor metastasis treatment.
      First, Brij78 (polyoxyethylene stearyl ether) was conjugated with Pamidronate
      (Pa). By incorporating Pa-Brij78 to DPPC/Chol liposomes, we developed Pa surface
      functionalized liposomes. The Pa-Brij78/DPPC/Chol liposomes (PB-liposomes)
      exhibited a stronger binding affinity to hydroxyapatite (HA), a major component
      of bone, than Brij78/DPPC/Chol liposomes (B-liposomes). Doxorubicin (Dox) was
      then encapsulated in PB-liposomes and the results demonstrated complete release
      of Dox from PB-liposomes or the complex of HA/PB-liposomes within 10 min at 42 
      degrees C. Next, human lung cancer A549 cells were treated with the
      thermosensitive complex of HA/PB-liposomes/Dox to mimic tumor bone metastasis
      treatment through bone targeted delivery of therapeutic agents. Pre-incubation of
      HA/PB-liposomes/Dox with mild heat at 42  degrees C induced subsequent higher
      cytotoxicity to A549 cells than incubation of the same complex at 37  degrees C,
      suggesting more active drug release triggered by heat. In conclusion, we
      synthesized a novel surfactant Pa-Brij78 and it has the potential to be used for
      development of a bone targeted thermosensitive liposome formulation for treatment
      of tumor bone metastasis. 

PMID- 25975586
TI  - A critical review on tablet disintegration.
AB  - CONTEXT: Tablet disintegration is an important factor for drug release and can be
      modified with excipients called tablet disintegrants. Tablet disintegrants act
      via different mechanisms and the efficacy of these excipients is influenced by
      various factors. OBJECTIVE: In this review, the existing literature on tablet
      disintegration is critically reviewed. Potential disintegration mechanisms, as
      well as impact factors on the disintegration process will be discussed based on
      experimental evidence. METHODS: Search terms for Scopus and Web of Science
      included "tablet disintegration", "mechanism tablet disintegration",
      "superdisintegrants", "disintegrants", "swelling force", "disintegration force",
      "disintegration mechanisms", as well as brand names of commonly applied
      superdisintegrants. References of identified papers were screened as well.
      RESULTS: Experimental data supports swelling and shape recovery as main
      mechanisms of action of disintegrants. Other tablet excipients and different
      manufacturing techniques greatly influence the disintegration process.
      CONCLUSION: The use of different excipients, experimental setups and
      manufacturing techniques, as well as the demand for original research led to a
      distinct patchwork of knowledge. Broader, more systematic approaches are
      necessary not only to structure the past but also future findings.

PMID- 25975587
TI  - New conformational polymorph of hydrochlorothiazide with improved solubility.
AB  - CONTEXT: To characterize a new conformation of hydrochlorothiazide (HCT) with
      better solubility and establishing its relationship with previously reported form
      I, obtained during attempted crystallization experiments. OBJECTIVE: The aim of
      present investigation is to unveil a new conformational polymorph (form IA)
      having a higher solubility compared to commercially available form I. MATERIALS
      AND METHODS: New form (IA) was obtained from slow evaporation as well as by
      solvent-antisolvent method and was then characterized by DSC, FTIR, PXRD and
      SCXRD. Equilibrium solubility profile shows that it is more soluble than form I.
      RESULTS: Appearance of phase transition endotherm at 215.87  degrees C in DSC
      spectra indicated the existence of new polymorph which was further confirmed by
      FTIR and PXRD. Single crystal study showed significant difference in various bond
      angles and torsion angles of the two forms. The solubility exhibited by form IA
      was (938 ug/mL) compared to form I (791 ug/mL) in water. DISCUSSION: Complete
      structural analysis and molecular arrangements in the unit cell along with the
      DSC and FTIR data confirm the existence of new conformer of HCT. CONCLUSION: This
      study reveals the existence of a new conformational polymorph of HCT molecule
      having higher solubility could prove to be promising in pre-formulation.

PMID- 25975588
TI  - Phase Behavior of Resveratrol Solid Dispersions Upon Addition to Aqueous media.
AB  - PURPOSE: To investigate the phase behavior of resveratrol amorphous solid
      dispersions upon addition to aqueous media. METHODS: Polymers with different
      crystallization inhibitor properties were used to form amorphous solid
      dispersions of resveratrol. Resveratrol crystallization in aqueous environments
      was monitored over time using Raman spectroscopy, and solution concentrations
      were determined by ultraviolet (UV) spectroscopy. RESULTS: The crystallization
      behavior varied depending on the type and amount of polymer present in the
      dispersion. Polyvinylpyrrolidone (PVP) and Eudragit E100 (E100) dispersions did
      not crystallize for 24 h when slurried in pH 6.8 buffer at 37 degrees C. Even
      though no crystallization occurred, a supersaturated solution was not achieved,
      most likely because of resveratrol-polymer complexation. Dispersions formed with
      cellulose derivatives crystallized rapidly, and the extent of crystallization
      varied depending on the amount of polymer in the dispersion. The solution
      concentration achieved in the slurries varied considerably between the various
      solid dispersions and depended on several factors including the extent of
      resveratrol crystallization, the nature of the resveratrol-polymer interactions,
      and the concentration of solid dispersion added to the slurry. CONCLUSIONS: It
      was found that the extent of supersaturation was limited not only by
      crystallization, but also by soluble and insoluble complex formation between
      resveratrol and the polymer.

PMID- 25975589
TI  - Screening Men with Coronary Heart Disease for Abdominal Aortic Aneurysm: A
      Prospective Cohort Study.
AB  - BACKGROUND: The prevalence of abdominal aortic aneurysms (AAA) is higher among
      patients with coronary heart disease (CHD) compared with control population.
      OBJECTIVE: To assess and determine the prevalence of non-diagnosed AAA in men
      with CHD. MATERIALS AND METHODS: A total of 438 active male out-patients with CHD
      were screened for AAA by abdominal ultrasound (US) examination. The largest
      infrarenal aortic dimension was registered. The patient was regarded to have AAA
      when the aortic diameter was greater than 30 mm. RESULTS: We found altogether 25
      AAAs. The incidence of AAA was 5.7%. One AAA patient was operated on, and the
      other AAA patients are under surveillance. Independent predictors for AAA among
      CHD patients were increased age, family history of AAA, and current or previous
      smoking. The screening process took on average 5 min per patient, and the cost of
      screening was 15<euro> ($18.50) per patient or <euro>257 ($325) per found AAA.
      CONCLUSIONS: The prevalence of previously undiagnosed AAAs among patients with
      CHD is considerable. Screening of AAA should be considered among active patients
      with CHD. The most feasible and simplest option would be to perform the screening
      during any routine or elective cardiac US by a cardiologist, and we recommend to
      adopt it as a standard practice.

PMID- 25975590
TI  - Rapid and retrievable recording of big data of time-lapse 3D shadow images of
      microbial colonies.
AB  - We formerly developed an automatic colony count system based on the time-lapse
      shadow image analysis (TSIA). Here this system has been upgraded and applied to
      practical rapid decision. A microbial sample was spread on/in an agar plate with
      90 mm in diameter as homogeneously as possible. We could obtain the results with
      several strains that most of colonies appeared within a limited time span.
      Consequently the number of colonies reached a steady level (Nstdy) and then
      unchanged until the end of long culture time to give the confirmed value (Nconf).
      The equivalence of Nstdy and Nconf as well as the difference of times for Nstdy
      and Nconf determinations were statistically significant at p < 0.001. Nstdy meets
      the requirement of practical routines treating a large number of plates. The
      difference of Nstdy and Nconf, if any, may be elucidated by means of retrievable
      big data. Therefore Nconf is valid for official documentation. 

PMID- 25975591
TI  - Postoperative care of cardiac surgery patients . . . Finishing what you started.

PMID- 25975592
TI  - Routine postoperative care of patients undergoing coronary artery bypass grafting
      on cardiopulmonary bypass.
AB  - The postoperative course of a patient undergoing cardiac surgery (CS) is dictated
      by a largely predictable set of interactions between disease-specific and
      therapeutic factors. ICU personnel need to quickly develop a detailed
      understanding of the patient's current status and how critical care resources can
      be used to promote further recovery and eventual independence from external
      support. The goal of this article is to describe a typical operative and
      postoperative course, with emphasis on the latter, and the diagnostic and
      therapeutic options necessary for the proper care of these patients. This paper
      will focus on coronary artery bypass grafting as a model for understanding the
      course of CS patients; however, many of the principles discussed are applicable
      to most cardiac surgery patients. 

PMID- 25975593
TI  - How should we manage arrest following cardiac surgery?
AB  - Perioperative arrest occurs in thousands of cardiac surgical patients annually,
      yet standard resuscitation methods are ineffective or potentially harmful. These
      "high risk, low volume" events typically occur in well-monitored patients in the
      highly specialized environment of the operating room or intensive care unit, with
      a short list of likely causes of arrest, making a protocolized approach to
      management feasible and desirable. An evidence-based guideline for resuscitation
      specific to the cardiac surgical patient was first published by Dunning et al in
      2009 and adopted by the European Resuscitation Council the following year. It
      emphasizes important deviations from advanced cardiac life support, including
      immediate defibrillation or pacing of arrhythmias before external compressions,
      if feasible within 1 minute, and avoidance of epinephrine due to potential
      rebound hypertension. In standard fashion, the rapid exclusion of reversible
      causes of arrest is followed by chest reopening within 5 minutes. This approach
      is now standard of care in most European countries and is under review for use in
      the United States by the Society of Thoracic Surgeons. The anesthesiologist, as
      either team leader or participant, plays a critical role in optimally managing
      arrests after cardiac surgery. Their familiarity with this new standard is
      essential to optimal patient outcomes. 

PMID- 25975594
TI  - Intensive care unit management of transcatheter aortic valve recipients.
AB  - Severe aortic stenosis is an increasingly prevalent disease that continues to be
      associated with significant mortality. Transcatheter aortic valve replacements
      have been used as an alternative to surgical aortic valve replacement in high
      risk patients with multiple comorbidities. In this review, we discuss
      postoperative considerations pertinent to the successful management of these
      complicated patients in the intensive care unit. 

PMID- 25975595
TI  - Management of postoperative atrial fibrillation in cardiac surgery patients.
AB  - Postoperative atrial fibrillation (AF) is a common arrhythmia following cardiac
      surgery and contributes to patient morbidity, prolonged hospital stay, and
      increased financial costs. The risk of postoperative AF may increase based on
      patient characteristics or events that occur intraoperatively or postoperatively.
      An understanding of these risks may be helpful in identifying which patients
      would benefit from prevention strategies. Acute AF presentation may range from
      completely indolent to rapidly progressing hemodynamic instability. Patients
      without hemodynamic compromise can be managed conservatively with rate control or
      initiation of antiarrhythmic medications. Patients with significant hemodynamic
      instability should undergo direct current cardioversion. In the postoperative
      period, it is reasonable to initiate anticoagulation after 48 hours of sustained
      AF or frequent episodes of postoperative AF. 

PMID- 25975596
TI  - Valvular heart disease and postoperative considerations.
AB  - Despite increasing trends in catheter-based cardiac surgical procedures, more
      than 278 000 Americans had traditional cardiac surgery in 2013. Of those surgical
      procedures, approximately 133 000 involved valvular repair or replacement. Aortic
      valve replacement was by far the most common valvular operation, followed by
      mitral valve repair or replacement. This review article will discuss
      characteristics of valvular pathologies and postoperative concerns for each the 4
      cardiac valves. 

PMID- 25975597
TI  - Postoperative care of the adult with congenital heart disease.
AB  - An increasing number of children with congenital heart disease survive to
      adulthood, but many adults require surgical intervention and can present complex
      management challenges in the perioperative period. This review will address
      common considerations that surgeons, anesthesiologists, and intensivists are
      likely to face in caring for this growing population. 

PMID- 25975598
TI  - Early extubation and fast-track management of off-pump cardiac patients in the
      intensive care unit.
AB  - Off-pump surgery was the original approach to treating patients with cardiac
      disease in the era before cardiopulmonary bypass. With the advent and refinement
      of cardiopulmonary bypass, the use of this technique fell out of favor and was
      quickly surpassed by on-pump techniques. However, the limitations of bypass
      surgery, especially for coronary artery bypass procedures, was still significant,
      leading to renewed interest in this technique. Postoperative care for off-pump
      coronary artery bypass (OPCAB) surgery presents both a challenge and opportunity
      to the intensivist. OPCAB patients can be treated in a fast-track manner allowing
      rapid recovery and early extubation and discharge from the intensive care unit.
      This is supported through the use of protocols that help standardize care and set
      expectations for the post-cardiac care team. Importantly, complications that may
      delay recovery including hypothermia, hypotension, and bleeding must be
      recognized early and treated aggressively to prevent unwanted complications and
      intensive care delays. Finally, care of these patients has shifted to the post
      anesthesia recovery room, making knowledge of the care of these patients in the
      early postoperative period essential for cardiac anesthesiologists. This article
      will discuss the care of OPCAB patients following surgery and include approaches
      to managing patients who return both intubated and extubated. 

PMID- 25975600
TI  - 3D silicone rubber interfaces for individually tailored implants.
AB  - For the fabrication of customized silicone rubber based implants, e.g. cochlear
      implants or electrocortical grid arrays, it is required to develop high speed
      curing systems, which vulcanize the silicone rubber before it runs due to a
      heating related viscosity drop. Therefore, we present an infrared radiation based
      cross-linking approach for the 3D-printing of silicone rubber bulk and carbon
      nanotube based silicone rubber electrode materials. Composite materials were
      cured in less than 120 s and material interfaces were evaluated with scanning
      electron microscopy. Furthermore, curing related changes in the mechanical and
      cell-biological behaviour were investigated with tensile and WST-1 cell
      biocompatibility tests. The infrared absorption properties of the silicone rubber
      materials were analysed with fourier transform infrared spectroscopy in
      transmission and attenuated total reflection mode. The heat flux was calculated
      by using the FTIR data, emissivity data from the infrared source manufacturer and
      the geometrical view factor of the system. 

PMID- 25975599
TI  - Genetics of drug response in type 2 diabetes.
AB  - The introduction of several new drug groups into the treatment of type 2 diabetes
      in the past few decades leads to an increased requirement for an individualized
      treatment approach. A personalized treatment is important from the point of view
      of both efficacy and safety. Recent guidelines are based mainly on entirely
      phenotypic characteristics such as diabetes duration, presence of macrovascular
      complications, or risk of hypoglycemia with the use of individual drugs. So far,
      genetic knowledge is used to guide treatment in the monogenic forms of diabetes.
      With the accumulating pharmacogenetic evidence in type 2 diabetes, there are
      reasonable expectations that genetics might help in the adjustment of drug doses
      to reduce severe side effects, as well as to make better therapeutic choices
      among the drugs available for the treatment of diabetes. 

PMID- 25975602
TI  - Response to: 'Questioning the significance of the non-identity problem in applied
      ethics' by Lawlor.

PMID- 25975601
TI  - Exposure to prescription opioid analgesics in utero and risk of neonatal
      abstinence syndrome: population based cohort study.
AB  - OBJECTIVE: To provide absolute and relative risk estimates of neonatal abstinence
      syndrome (NAS) based on duration and timing of prescription opioid use during
      pregnancy in the presence or absence of additional NAS risk factors of history of
      opioid misuse or dependence, misuse of other substances, non-opioid psychotropic
      drug use, and smoking. DESIGN: Observational cohort study. SETTING: Medicaid data
      from 46 US states. PARTICIPANTS: Pregnant women filling at least one prescription
      for an opioid analgesic at any time during pregnancy for whom opioid exposure
      characteristics including duration of therapy: short term (<30 days) or long term
      (>= 30 days); timing of use: early use (only in the first two trimesters) or late
      use (extending into the third trimester); and cumulative dose (in morphine
      equivalent milligrams) were assessed. MAIN OUTCOME MEASURE: Diagnosis of NAS in
      liveborn infants. RESULTS: 1705 cases of NAS were identified among 290,605
      pregnant women filling opioid prescriptions, corresponding to an absolute risk of
      5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid
      use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries
      in the presence of additional risk factors of known opioid misuse (220.2 (200.8
      to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other
      psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6))
      than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The
      corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0
      (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000
      deliveries, respectively. In propensity score matched analyses, long term
      prescription opioid use compared with short term use and late use compared with
      early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95%
      confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively).
      CONCLUSIONS: Use of prescription opioids during pregnancy is associated with a
      low absolute risk of NAS in the absence of additional risk factors. Long term use
      compared with short term use and late use compared with early use of prescription
      opioids are associated with increased NAS risk independent of additional risk
      factors.

PMID- 25975603
TI  - Overexpression of hypoxia-inducible factor prolyl hydoxylase-2 attenuates hypoxia
      induced vascular endothelial growth factor expression in luteal cells.
AB  - Vascular endothelial growth factor (VEGF)-dependent angiogenesis has a crucial
      role in the corpus luteum formation and their functional maintenances in
      mammalian ovaries. A previous study by our group reported that activation of
      hypoxia-inducible factor (HIF)-1alpha signaling contributes to the regulation of
      VEGF expression in the luteal cells (LCs) in response to hypoxia and human
      chorionic gonadotropin. The present study was designed to test the hypothesis
      that HIF prolyl-hydroxylases (PHDs) are expressed in LCs and overexpression of
      PHD2 attenuates the expression of VEGF induced by hypoxia in LCs. PHD2
      overexpressing plasmid was transfected into LC2 cells, and successful plasmid
      transfection and expression was confirmed by reverse transcription quantitative
      polymerase chain reaction and western blot analysis. In addition, the present
      study investigated changes of HIF-1alpha and VEGF expression after incubation
      under hypoxic conditions and PHD2 transfection. PHD2 expression was significantly
      higher expressed than the other two PHD isoforms, indicating its major role in
      LCs. Moreover, a significant increase of VEGF mRNA expression was identified
      after incubation under hypoxic conditions, which was, however, attenuated by PHD2
      overexpression in LCs. Further analysis also indicated that this hypoxia-induced
      increase in the mRNA expression of VEGF was consistent with increases in the
      protein levels of HIF-1alpha, which is regulated by PHD-mediated degradation. In
      conclusion, the results of the present study indicated that PHD2 is the main PHD
      expressed in LCs and hypoxia-induced VEGF expression can be attenuated by PHD2
      overexpression through HIF-1alpha-mediated mechanisms in LCs. This PHD2-mediated
      transcriptional activation may be one of the mechanisms regulating VEGF
      expression in LCs during mammalian corpus luteum development.

PMID- 25975604
TI  - Iron deficiency may lead to false diagnosis of diabetes.

PMID- 25975605
TI  - Emerging optical methods for surveillance of Barrett's oesophagus.
AB  - The rapid rise in incidence of oesophageal adenocarcinoma has motivated the need
      for improved methods for surveillance of Barrett's oesophagus. Early neoplasia is
      flat in morphology and patchy in distribution and is difficult to detect with
      conventional white light endoscopy (WLE). Light offers numerous advantages for
      rapidly visualising the oesophagus, and advanced optical methods are being
      developed for wide-field and cross-sectional imaging to guide tissue biopsy and
      stage early neoplasia, respectively. We review key features of these promising
      methods and address their potential to improve detection of Barrett's neoplasia.
      The clinical performance of key advanced imaging technologies is reviewed,
      including (1) wide-field methods, such as high-definition WLE, chromoendoscopy,
      narrow-band imaging, autofluorescence and trimodal imaging and (2) cross
      sectional techniques, such as optical coherence tomography, optical frequency
      domain imaging and confocal laser endomicroscopy. Some of these instruments are
      being adapted for molecular imaging to detect specific biological targets that
      are overexpressed in Barrett's neoplasia. Gene expression profiles are being used
      to identify early targets that appear before morphological changes can be
      visualised with white light. These targets are detected in vivo using exogenous
      probes, such as lectins, peptides, antibodies, affibodies and activatable enzymes
      that are labelled with fluorescence dyes to produce high contrast images. This
      emerging approach has potential to provide a 'red flag' to identify regions of
      premalignant mucosa, outline disease margins and guide therapy based on the
      underlying molecular mechanisms of cancer progression. 

PMID- 25975606
TI  - Colossal positive magnetoresistance in surface-passivated oxygen-deficient
      strontium titanite.
AB  - Modulation of resistance by an external magnetic field, i.e. magnetoresistance
      effect, has been a long-lived theme of research due to both fundamental science
      and device applications. Here we report colossal positive magnetoresistance
      (CPMR) (>30,000% at a temperature of 2 K and a magnetic field of 9 T) discovered
      in degenerate semiconducting strontium titanite (SrTiO3) single crystals capped
      with ultrathin SrTiO3/LaAlO3 bilayers. The low-pressure high-temperature
      homoepitaxial growth of several unit cells of SrTiO3 introduces oxygen vacancies
      and high-mobility carriers in the bulk SrTiO3, and the three-unit-cell LaAlO3
      capping layer passivates the surface and improves carrier mobility by suppressing
      surface-defect-related scattering. The coexistence of multiple types of carriers
      and inhomogeneous transport lead to the emergence of CPMR. This unit-cell-level
      surface engineering approach is promising to be generalized to others oxides, and
      to realize devices with high-mobility carriers and interesting magnetoelectronic
      properties. 

PMID- 25975608
TI  - Informal carers' health-related quality of life and patient experience in primary
      care: evidence from 195,364 carers in England responding to a national survey.
AB  - BACKGROUND: We aim to describe the health-related quality of life of informal
      carers and their experiences of primary care. METHODS: Responses from the 2011-12
      English General Practice Patient Survey, including 195,364 informal carers, were
      analysed using mixed effect logistic regressions controlling for age, gender,
      ethnicity and social deprivation to describe carer health-related quality of life
      (mobility, self-care, usual activities, pain, and anxiety/depression, measured
      using EQ-5D) and primary care experience (access, continuity and communication).
      RESULTS: Informal carers reported poorer health-related quality of life than non
      carers of similar age, gender, ethnicity and social deprivation. Increasing
      caring commitment was associated with worse EQ-5D scores, with carers of 50+
      hours a week scoring 0.05 points lower than non-carers (95 % CI 0.05 to 0.04),
      equivalent to 18 fewer days of full health annually. Considering each domain of
      EQ-5D separately, carers of 50+ hours/week were more likely to report pain OR =
      1.53 (1.50-1.57), p < 0.0001, and anxiety/depression OR = 1.69 (1.66-1.73), p <
      0.0001, than non-carers. Younger carers scored lower on EQ-5D than non-carer
      peers but the converse was true among over-85s. In the most deprived areas carers
      reported the equivalent of 37 fewer days of full health annually than carers in
      the most affluent areas. On average, carers reported poorer patient experiences
      in all areas of primary care than non-carers (odds ratios 0.84-0.97), with this
      difference being most marked in the domain of access. CONCLUSIONS: Informal
      carers experience a double disadvantage of poorer health-related quality of life
      and poorer patient experience in primary care. We find no evidence for health
      benefits of caregiving. We recommend physicians identify and treat carer health
      problems, including pain and anxiety/depression, particularly among young,
      deprived and high time-commitment carers. Improving patient experience for
      carers, including access to primary care, should be a priority.

PMID- 25975609
TI  - Professional practice models for nursing: a review of the literature and
      synthesis of key components.
AB  - AIM: This review aimed to synthesise literature describing the development and/or
      implementation and/or evaluation of a professional practice model to determine
      the key model components. BACKGROUND: A professional practice model depicts
      nursing values and defines the structures and processes that support nurses to
      control their own practice and to deliver quality care. EVALUATION: A review of
      English language papers published up to August 2014 identified 51 articles that
      described 38 professional practice models. Articles were subjected to qualitative
      analysis to identify the concepts common to all professional practice models. KEY
      ISSUE: Key elements of professional practice models were theoretical foundation
      and six common components: leadership; nurses' independent and collaborative
      practice; environment; nurse development and reward; research/innovation; and
      patient outcomes. CONCLUSIONS: A professional practice model provides the
      foundations for quality nursing practice. This review is an important resource
      for nurse leaders who seek to advance their organisation in a journey for
      excellence through the implementation of a professional practice model.
      IMPLICATIONS FOR NURSING MANAGEMENT: This summary of published professional
      practice models provides a guide for nurse leaders who seek to develop a
      professional practice model. The essential elements of a professional practice
      model; theoretical foundation and six common components, are clearly described.
      These elements can provide the starting point for nurse leaders' discussions with
      staff to shape a professional practice model that is meaningful to direct care
      nurses.

PMID- 25975607
TI  - Pattern recognition receptors as potential therapeutic targets in inflammatory
      rheumatic disease.
AB  - The pattern recognition receptors of the innate immune system are part of the
      first line of defence against pathogens. However, they also have the ability to
      respond to danger signals that are frequently elevated during tissue damage and
      at sites of inflammation. Inadvertent activation of pattern recognition receptors
      has been proposed to contribute to the pathogenesis of many conditions including
      inflammatory rheumatic diseases. Prolonged inflammation most often results in
      pain and damage to tissues. In particular, the Toll-like receptors and nucleotide
      binding oligomerisation domain-like receptors that form inflammasomes have been
      postulated as key contributors to the inflammation observed in rheumatoid
      arthritis, osteoarthritis, gout and systemic lupus erythematosus. As such, there
      is increasing interest in targeting these receptors for therapeutic treatment in
      the clinic. Here the role of pattern recognition receptors in the pathogenesis of
      these diseases is discussed, with an update on the development of interventions
      to modulate the activity of these potential therapeutic targets. 

PMID- 25975610
TI  - Role of LuxIR Homologue AnoIR in Acinetobacter nosocomialis and the Effect of
      Virstatin on the Expression of anoR Gene.
AB  - Quorum sensing is a process of cell-to-cell communication in which bacteria
      produce autoinducers as signaling molecules to sense cell density and coordinate
      gene expression. In the present study, a LuxI-type synthase, AnoI, and a LuxR
      type regulator, AnoR, were identified in Acinetobacter nosocomialis, an important
      nosocomial pathogen, by sequence analysis of the bacterial genome. We found that
      N-(3-hydroxy-dodecanoyl)-L-homoserine lactone (OH-dDHL) is a quorum-sensing
      signal in A. nosocomialis. The anoI gene deletion was responsible for the
      impairment in the production of OH-dDHL. The expression of anoI was almost
      abolished in the anoR mutant. These results indicate that AnoI is essential for
      the production of OH-dDHL in A. nosocomialis, and its expression is positively
      regulated by AnoR. Moreover, the anoR mutant exhibited deficiency in biofilm
      formation. In particular, motility of the anoR mutant was consistently and
      significantly abolished compared with that of the wild type. The deficiency in
      the biofilm formation and motility of the anoR mutant was significantly restored
      by a functional anoR , indicating that AnoR plays important roles in the biofilm
      formation and motility. Furthermore, the present study showed that virstatin
      exerts its effects on the reduction of biofilm formation and motility by
      inhibiting the expression of anoR . Consequently, the combined results suggest
      that AnoIR is a quorum-sensing system that plays important roles in the biofilm
      formation and motility of A. nosocomialis, and virstatin is an inhibitor of the
      expression of anoR.

PMID- 25975611
TI  - Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in
      Fischer 344 Rats.
AB  - To investigate the memory-enhancing effect of lactic acid bacteria, we selected
      the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and
      Lactobacillus curvatus HY7601 (1 * 10(11) CFU/g of each strain), and investigated
      its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 *
      10(10) CFU/rat/day), which was administered orally once a day (6 days per week)
      for 8 weeks, significantly inhibited age-dependent increases of blood
      triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced
      spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p
      < 0.05). KF treatment slightly, but not significantly, shortened the escape
      latency daily for 4 days. Oral administration of KF restored age-suppressed
      doublecortin and brain-derived neurotrophic factor expression in aged rats.
      Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase
      2, the phosphorylation of Akt and mTOR, and the activation of NF-kappaB in the
      hippocampus of the brain. These findings suggest that KF may ameliorate age
      dependent memory deficit and lipidemia by inhibiting NF-kappaB activation.

PMID- 25975612
TI  - Isolation of the Phosphoribosyl Anthranilate Isomerase Gene (TRP1) from Starch
      Utilizing Yeast Saccharomycopsis fibuligera.
AB  - The nucleotide sequence of the TRP1 gene encoding phosphoribosyl anthranilate
      isomerase in yeast Saccharomycopsis fibuligera was determined by degenerate
      polymerase chain reaction and genome walking. Sequence analysis revealed the
      presence of an uninterrupted open-reading frame of 759 bp, including the stop
      codon, encoding a 252 amino acid residue. The deduced amino acid sequence of Trp1
      in S. fibuligera was 43.5% homologous to that of Komagataella pastoris. The
      cloned TRP1 gene (SfTRP1) complemented the trp1 mutation in Saccharomyces
      cerevisiae, suggesting that it encodes a functional TRP1 in S. fibuligera. A new
      auxotrophic marker to engineer starch-degrading yeast S. fibuligera is now
      available. The GenBank Accession No. for SfTRP1 is KR078268.

PMID- 25975613
TI  - Ycs4 is Required for Efficient Double-Strand Break Formation and Homologous
      Recombination During Meiosis.
AB  - Condensin is not only responsible for chromosome condensation, but is also
      involved in double-strand break (DSB) processing in the cell cycle. During
      meiosis, the condensin complex serves as a component of the meiotic chromosome
      axis, and mediates both proper assembly of the synaptonemal complex and DSB
      repair, in order to ensure proper homologous chromosome segregation. Here, we
      used the budding yeast Saccharomyces cerevisiae to show that condensin
      participates in a variety of chromosome organization processes and exhibits
      crucial molecular functions that contribute to meiotic recombination during
      meiotic prophase I. We demonstrate that Ycs4 is required for efficient DSB
      formation and establishing homolog bias at the early stage of meiotic prophase I,
      which allows efficient formation of interhomolog recombination products. In the
      Ycs4 meiosis-specific allele (ycs4S), interhomolog products were formed at
      substantial levels, but with the same reduction in crossovers and noncrossovers.
      We further show that, in prophase chromosomal events, ycs4S relieved the defects
      in the progression of recombination interactions induced as a result of the
      absence of Rec8. These results suggest that condensin is a crucial coordinator of
      the recombination process and chromosome organization during meiosis. 

PMID- 25975614
TI  - Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli.
AB  - The flavonoid apigenin and its O-methyl derivative, genkwanin, have various
      biological activities and can be sourced from some vegetables and fruits.
      Microorganisms are an alternative for the synthesis of flavonoids. Here, to
      synthesize genkwanin from tyrosine, we first synthesized apigenin from p-coumaric
      acid using four genes (4CL, CHS, CHI, and FNS) in Escherichia coli. After
      optimization of different combinations of constructs, the yield of apigenin was
      increased from 13 mg/l to 30 mg/l. By introducing two additional genes (TAL and
      POMT7) into an apigenin-producing E. coli strain, we were able to synthesize 7-O
      methyl apigenin (genkwanin) from tyrosine. In addition, the tyrosine content in
      E. coli was modulated by overexpressing aroG and tyrA. The engineered E. coli
      strain synthesized approximately 41 mg/l genkwanin. 

PMID- 25975615
TI  - Wave energy budget analysis in the Earth's radiation belts uncovers a missing
      energy.
AB  - Whistler-mode emissions are important electromagnetic waves pervasive in the
      Earth's magnetosphere, where they continuously remove or energize electrons
      trapped by the geomagnetic field, controlling radiation hazards to satellites and
      astronauts and the upper-atmosphere ionization or chemical composition. Here, we
      report an analysis of 10-year Cluster data, statistically evaluating the full
      wave energy budget in the Earth's magnetosphere, revealing that a significant
      fraction of the energy corresponds to hitherto generally neglected very oblique
      waves. Such waves, with 10 times smaller magnetic power than parallel waves,
      typically have similar total energy. Moreover, they carry up to 80% of the wave
      energy involved in wave-particle resonant interactions. It implies that electron
      heating and precipitation into the atmosphere may have been significantly
      under/over-valued in past studies considering only conventional quasi-parallel
      waves. Very oblique waves may turn out to be a crucial agent of energy
      redistribution in the Earth's radiation belts, controlled by solar activity. 

PMID- 25975616
TI  - Model-Based Determination of Effective Blood Concentrations of Cyclosporine for
      Neutrophil Response in the Treatment of Severe Aplastic Anemia in Children.
AB  - Optimal immunosuppressive therapy in acquired severe aplastic anemia (SAA)
      remains to be refined, especially cyclosporine (CsA) use. Current recommendations
      state that CsA trough blood concentrations (TBC) should be maintained between 200
      and 400 ng/mL despite the lack of supporting data. This study aimed at
      quantifying relationships between CsA exposure and neutrophil response and
      determining an effective range for CsA TBC. Twenty-three SAA patients treated
      with CsA were retrospectively analyzed. Nonlinear mixed effect modeling
      approaches were used to develop a pharmacokinetic-pharmacodynamic model. The
      pharmacokinetic model described the relationships between CsA doses and TBC. The
      pharmacodynamic model allowed to estimate boundaries for optimal CsA effects,
      neutrophils being used as biomarker of response. A time-to-event model linked
      effective concentration to time-to-therapeutic success. CsA TBC were adequately
      described by a two-compartment model with first-order absorption, a lag time, and
      a linear elimination. The efficient range of CsA TBC was estimated between 87 and
      120 ng/mL. Model-based simulations and external validation in three additional
      patients confirmed these results. This original modeling approach was successful
      in describing the relationship between CsA TBC and neutrophil response in SAA
      patients. Although further evaluation of the model is necessary, this work
      suggests that an optimal CsA TBC target of 100 ng/mL would be associated with a
      better neutrophil response in children with SAA.

PMID- 25975617
TI  - Utilizing Internal Standard Responses to Assess Risk on Reporting Bioanalytical
      Results from Hemolyzed Samples.
AB  - Bioanalytical analysis of toxicokinetic and pharmacokinetic samples is an
      integral part of small molecule drugs development and liquid chromatography
      tandem mass spectrometry (LC-MS/MS) has been the technique of choice. One
      important consideration is the matrix effect, in which ionization of the analytes
      of interest is affected by the presence of co-eluting interfering components
      present in the sample matrix. Hemolysis, which results in additional endogenous
      components being released from the lysed red blood cells, may cause additional
      matrix interferences. The effects of the degree of hemolysis on the accuracy and
      precision of the method and the reported sample concentrations from hemolyzed
      study samples have drawn increasing attention in recent years, especially in
      cases where the sample concentrations are critical for pharmacokinetic
      calculation. Currently, there is no established procedure to objectively assess
      the risk of reporting potentially inaccurate bioanalytical results from hemolyzed
      study samples. In this work, we evaluated the effect of different degrees of
      hemolysis on the internal standard peak area, accuracy, and precision of the
      analyses of BMS-906024 and its metabolite, BMS-911557, in human plasma by LC
      MS/MS. In addition, we proposed the strategy of using the peak area of the stable
      isotope-labeled internal standard (SIL-IS) from the LC-MS/MS measurement as the
      surrogate marker for risk assessment. Samples with peak areas outside of the pre
      defined acceptance criteria, e.g., less than 50% or more than 150% of the average
      IS response in study samples, plasma standards, and QC samples when SIL-IS is
      used, are flagged out for further investigation. 

PMID- 25975618
TI  - Erratum to: A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs:
      Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion.

PMID- 25975619
TI  - Biodegradation of Tributyltin (TBT) by Extremophile Bacteria from Atacama Desert
      and Speciation of Tin By-products.
AB  - Biodegradation of tributyltin (TBT) by four tin resistant Gram negative bacteria
      isolated from extremely contaminated river sediments in the Atacama Desert in
      Chile was studied. Moraxella osloensis showed the greatest resistance and
      degradation capability of TBT, producing less toxic by-products, such as
      dibutyltin (DBT) and inorganic tin. In 7 days, approximately 80 % of TBT
      degradation was achieved, generating close to 20 % of DBT as degradation product.
      The degradation rate constant (k) was 0.022 [day(-1)] and TBT half-life (t1/2) in
      culture was 4.3 days. Debutylation is stated a probable mechanism of TBT
      degradation.

PMID- 25975620
TI  - Mitochondrial dysfunctions during progression of dystrophic cardiomyopathy.
AB  - Duchenne muscular dystrophy (DMD) is a progressive muscle disease with severe
      cardiac complications. It is believed that cellular oxidative stress and
      augmented Ca(2+) signaling drives the development of cardiac pathology. Some
      mitochondrial and metabolic dysfunctions have also been reported. Here we
      investigate cellular mechanisms responsible for impaired mitochondrial metabolism
      in dystrophic cardiomyopathy at early stages of the disease. We employed
      electrophysiological and imaging techniques to study mitochondrial structure and
      function in cardiomyocytes from mdx mice, an animal model of DMD. Here we show
      that mitochondrial matrix was progressively oxidized in myocytes isolated from
      mdx mice. Moreover, an abrupt increase in workload resulted in significantly more
      pronounced oxidation of mitochondria in dystrophic cells. Electron micrographs
      revealed a gradually increased number of damaged mitochondria in mdx myocytes.
      Degradation in mitochondrial structure was correlated with progressive increase
      in mitochondrial Ca(2+) sequestration and mitochondrial depolarization, despite a
      substantial and persistent elevation in resting cytosolic sodium levels.
      Treatment of mdx cells with cyclosporine A, an inhibitor of mitochondrial
      permeability transition pore (mPTP), shifted both resting and workload-dependent
      mitochondrial redox state to the levels recorded in control myocytes. It also
      significantly reduced workload dependent depolarization of mitochondrial membrane
      in dystrophic cardiomyocytes. Overall, our studies highlight age dependent
      deterioration of mitochondrial function in dystrophic cardiomyocytes, which seems
      to be associated with excessive opening of mPTP due to oxidative stress and
      cellular Ca(2+) overload. 

PMID- 25975621
TI  - Comparison of osteoarticular allograft reconstruction with and without the Sauve
      Kapandji procedure following tumour resection in distal radius.
AB  - BACKGROUND: The purpose of this study was to compare the midterm functional and
      oncological outcomes of patients with distal radial tumours treated with en bloc
      tumour excision and osteoarticular allograft reconstruction with or without a
      Sauve-Kapandji (S-K) procedure. MATERIALS AND METHOD: All cases of osteoarticular
      allograft reconstruction with or without the S-K procedure following resection of
      distal radial tumours (giant-cell tumour in 13, desmoplastic fibroma in two,
      osteosarcoma in one and malignant fibrous histiocytoma in one) performed from
      2000 to 2009 were evaluated by clinical and radiologic examinations; the
      complications, functional outcomes and Musculoskeletal Tumor Society (MSTS) score
      were recorded. RESULTS: Seventeen patients (seven with the S-K procedure and 10
      without the S-K procedure) with an average age of 31.8 years formed the study
      population. The follow-up time averaged 84.7 months. All patients continued to be
      disease-free except one with a local relapse. The reconstructive complications
      included non-union of radio allograft in one, allograft fracture in five, rupture
      of tendon in two and degenerative joint disease in all cases. Patients with the S
      K procedure had better range of rotation (P = 0.040), greater grip power (P =
      0.028) and less degenerative changes (P = 0.014) than those without the S-K
      procedure. Patients with additional S-K procedure tended to have a higher MSTS
      score (P = 0.073). CONCLUSIONS: En bloc resection of tumour in the distal radius
      followed by reconstruction with an osteoarticular allograft results in
      satisfactory oncologic and functional outcomes. Addition of the S-K procedure
      could improve functional outcomes with regard to allograft reconstruction.
      Evidence Rating Scale for Therapeutic Studies: Level III.

PMID- 25975622
TI  - Prospective Study on the Relationship of Obesity to Asthma Impairment and Risk.
AB  - BACKGROUND: Although studies consistently show an association between obesity and
      increased asthma incidence, the role of obesity in asthma control is less clear.
      OBJECTIVE: The objective of this study was to evaluate the association between
      baseline body mass index (BMI) and measures of subsequent asthma control in a
      large real-world cohort of adults with persistent asthma. METHODS: In Kaiser
      Permanente Southern California (KPSC), a large managed care organization, we
      identified adults with persistent asthma in 2006, continuous health plan
      enrollment in 2007 and 2008, and a BMI measurement in 2006 or 2007. Each
      patient's last BMI measure in 2006 or 2007 was categorized into a BMI group:
      normal (<25 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (>=30 kg/m(2)).
      Asthma control outcomes in 2008 included asthma hospitalizations or emergency
      department visits (EDHO), oral corticosteroid dispensings linked to an asthma
      encounter (OCS), and dispensing of >=7 short-acting beta-agonist canisters
      (SABA7). Multivariable analyses were conducted to assess the relationships of BMI
      categories with the risk of the asthma control outcomes after controlling for
      potential confounders. RESULTS: In the 10,233 eligible adults-after adjusting for
      potential demographic, comorbidity, and prior utilization confounders-we found an
      increased relative risk (RR) of EDHO in overweight and obese (RR 1.40, 95% CI
      1.10-1.78) individuals. Only obesity was associated in adjusted analyses with a
      significant increased relative risk of SABA7 (RR 1.27, 95% CI 1.15-1.40).
      CONCLUSIONS: Elevated BMI, particularly obesity, is associated with subsequent
      poor asthma control, especially in the risk domain (exacerbations). These
      findings further support the importance of facilitating weight loss in overweight
      and obese adults with asthma.

PMID- 25975624
TI  - Investigating the dynamics of recombinant protein secretion from a microalgal
      host.
AB  - Production of recombinant proteins with microalgae represents an alternative
      platform over plant- or bacterial-based expression systems for certain target
      proteins. Secretion of recombinant proteins allows accumulation of the target
      product physically separate from the valuable algal biomass. To date, there has
      been little investigation into the dynamics of recombinant protein secretion from
      microalgal hosts-the culture parameters that encourage secreted product
      accumulation and stability, while encouraging biomass production. In this work,
      the efficiency of recombinant protein production was optimized by adjusting
      cultivation parameters for a strain of Chlamydomonas reinhardtii previously
      engineered to secrete a functional recombinant Lolium perenne ice binding protein
      (LpIBP), which has applications as a frozen food texturing and cryopreservation
      additive, into its culture medium. Three media and several cultivation styles
      were investigated for effects on secreted LpIBP titres and culture growth. A
      combination of acetate and carbon dioxide feeding with illumination resulted in
      the highest overall biomass and recombinant protein titres up to 10mgL(-1) in the
      culture medium. Pure photoautotrophic production was possible using two media
      types, with recombinant protein accumulation in all cultivations correlating to
      culture cell density. Two different cultivation systems were used for scale-up to
      10L cultivations, one of which produced yields of secreted recombinant protein up
      to 12mgL(-1) within six cultivation days. Functional ice recrystallization
      inhibition (IRI) of the LpIBP from total concentrated extracellular protein
      extracts was demonstrated in a sucrose solution used as a simplified ice cream
      model. IRI lasted up to 7 days, demonstrating the potential of secreted products
      from microalgae for use as food additives. 

PMID- 25975623
TI  - Childhood sensorineural hearing loss: effects of combined exposure with aging or
      noise exposure later in life.
AB  - The aim of the study was to examine childhood high-frequency sensorineural
      hearing loss (HF-SNHL) and the effects of combined exposure with aging or noise
      exposure on HF hearing thresholds in adulthood. Population-based cohort study of
      30,003 adults (mean age 40 years) underwent an audiometry and completed a hearing
      questionnaire. At age 7-13 years, the same people had participated in a
      longitudinal school hearing investigation, in which 283 participants were
      diagnosed with HF-SNHL [PTA 3-8 kHz >= 25 dB HL (mean 45 dB HL), worse hearing
      ear], and 29,720 participants had normal hearing thresholds. The effect of
      childhood HF-SNHL on adult hearing threshold was significantly moderated by age.
      Age stratified analyses showed that the difference in HF hearing thresholds
      between adults with and without childhood HF-SNHL was 33 dB (95 % CI 31-34) in
      young adults (n = 173, aged 20-39 years) and 37 dB (95 % CI 34-39) in middle-aged
      adults (n = 110, aged 40-56 years). The combined exposure of childhood HF-SNHL
      and noise exposure showed a simple additive effect. It appears to be a super
      additive effect of childhood-onset HF-SNHL and aging on adult hearing thresholds.
      An explanation might be that already damaged hair cells are more susceptible to
      age-related degeneration. To exclude possible birth cohort effects, the finding
      should be confirmed by a study with several audiometries in adulthood.

PMID- 25975625
TI  - Complete genome sequence of Serratia multitudinisentens RB-25(T), a novel
      chitinolytic bacterium.
AB  - Serratia multitudinisentens RB-25(T) (=DSM 28811(T) =LMG 28304(T)) is a newly
      proposed type strain in the genus of Serratia isolated from a municipal landfill
      site. Here, we present the complete genome of S. multitudinisentens RB-25(T)
      which contains a complete chitinase operon and other chitin and N
      acetylglucosamine utilisation enzymes. To our knowledge, this is the first report
      of the complete genome sequence of this novel isolate and its chitinase gene
      discovery. 

PMID- 25975626
TI  - Which are important targets in development of S. aureus mastitis vaccine?
AB  - Staphylococcus aureus represents one of the leading causes of mastitis in dairy
      cows worldwide. S. aureus IMI have variable outcomes due to virulence of the
      strain involved, immune defenses of the host, and by antibiotic resistance. The
      difficulty in eradication and the increasing concerns on antibiotics usages
      underscore the interest in developing new tools to control S. aureus mastitis.
      Vaccination represents one of the most studied of these tools but, so far, no
      vaccine seems to provide reliable protection. This review summarizes current
      knowledge on the major vaccine targets, including surface proteins, capsular
      polysaccharides, biofilm, and toxins. Finally, the present status of vaccination
      against S. aureus and the future of vaccine design were discussed, including how
      differences among in vivo models may influence vaccines development. 

PMID- 25975627
TI  - Evaluation of an indirect ELISA using recombinant granule antigen GRA1, GRA7 and
      soluble antigens for serodiagnosis of Toxoplasma gondii infection in chickens.
AB  - In the present study, recombinant granule antigen proteins GRA1, GRA7 and
      Toxoplasma soluble antigens (TSA) were evaluated as potential diagnostic markers
      for T. gondii infection in chickens by an indirect enzyme-linked immunosorbent
      assay (ELISA), showing a seroprevalence of 16.4% by GRA1-ELISA, and 15.5% by both
      GRA7- and TSA-ELISA in chickens. No significant difference was observed in the
      inconsistent results (P > 0.05), and a substantial agreement was found in the
      consistent results of the 3 tests (92.7-97.3%). Compared with the reference test
      Western blot, GRA7-ELISA showed the highest co-positivity and co-negativity
      rates. Receiver operating characteristic (ROC) analysis revealed a largest area
      under curve (AUC) of 0.99 (95% CI, 98-1.0), and a highest relative sensitivity
      (100%) and specificity (97.9%) for a cut-off value of 0.34 in GRA7-ELISA. These
      results of the present study showed that GRA7 is a potential diagnostic marker
      for the detection of T. gondii infection in chickens. 

PMID- 25975628
TI  - Activity Participation and Sensory Features Among Children with Autism Spectrum
      Disorders.
AB  - Sensory features are highly prevalent among children with autism spectrum
      disorders (ASD) and have been shown to cluster into four patterns of response,
      including hyperresponsiveness, hyporesponsiveness, enhanced perception, and
      sensory interests, repetitions and seeking behaviors. Given the lack of large
      scale research on the differential effects of sensory response patterns on
      children's participation in specific activities, this study investigated the
      extent to which sensory response patterns impacted six dimensions of children's
      activity participation as measured by the Home and Community Activities Scale
      among a large, national sample of school aged children with ASD (n = 674). Using
      mixed model regression, results showed that sensory response patterns
      differentially impacted dimensions of activity participation, and associations
      were moderated by a number of child characteristics.

PMID- 25975630
TI  - [Not Available].

PMID- 25975629
TI  - Preoperative anaemia and newly diagnosed cancer 1 year after elective total hip
      and knee arthroplasty.
AB  - BACKGROUND: Preoperative anaemia is a well-established risk factor for use of
      blood transfusions and postoperative morbidity. Consequently, focus on
      preoperative evaluation of haemoglobin levels is increasing. In this context,
      iron deficiency anaemia may be a symptom of undiscovered gastrointestinal (GI)
      cancer requiring further investigation. However, the association between
      preoperative anaemia and cancer 1 year after elective total hip (THA) and total
      knee arthroplasty (TKA) is unknown. We evaluated 1-year cancer diagnoses,
      particularly GI cancers, in anaemic and non-anaemic THA and TKA patients. STUDY
      DESIGN AND METHODS: A prospective database on preoperative patient
      characteristics from six Danish orthopaedic centres was cross-referenced with the
      Danish Cancer Registry for information on diagnoses of new cancers 1 year after
      surgery. Crude cancer risk estimates were calculated using chi-square and
      Fisher's exact test in the total study cohort. Adjusted risk estimates were
      obtained using propensity scores and the Mantel-Haenzel statistic. RESULTS: Of
      5400 procedures, 731 (13.5%) were in anaemic patients. These were older and had
      more comorbidity than non-anaemic patients. There were 17 (2.3%) and 79 (1.6%)
      new cancers in anaemic and non-anaemic patients, respectively (OR: 1.38; 95% CI:
      0.81-2.35, P = 0.228). After propensity matching of 661 anaemic and 1305 non
      anaemic patients, we found no association between preoperative anaemia and cancer
      (OR: 0.94; 95% CI: 0.51-1.73, P = 0.837) or with GI cancers specifically (OR:
      0.80; 95% CI: 0.25-2.56, P = 0.707). CONCLUSION: Preoperative anaemia per se may
      not be related to being diagnosed with cancer 1 year after THA and TKA. The
      optimal criteria for preoperative referral of anaemic patients to
      gastroenterologist in elective THA and TKA need further investigation.

PMID- 25975631
TI  - Noncontrast computed tomography factors that predict the renal stone outcome
      after shock wave lithotripsy.
AB  - OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) is a popular treatment
      for nephrolithiasis. We took advantage of noncontrast abdominal computed
      tomography (NCCT) to search the possible prognostic factors including abdominal
      fat distribution influencing stone-free rate. METHODS: From August 2008 to August
      2010, 145 patients who had renal calculus and had undergone ESWL were
      retrospectively reviewed. All of them received NCCT assessment before ESWL and
      were followed up after 1 month for stone clearance. These patients were divided
      into two groups: one was the stone-free group and the other was the residual
      stone group. Affecting parameters included stone size, location, stone surface
      area, Hounsfield unit density (HU density), skin-to-stone distance (SSD), and
      abdominal fat area as analyzed between these two groups. RESULTS: Of 145
      patients, 70 were stone-free and 75 had residual stone after ESWL treatment and 1
      month follow-up. From univariate analysis, stone size, HU density, SSD, and stone
      surface area were significant predicting factors for ESWL success. On
      multivariate analysis, the important factors influencing ESWL outcomes were HU
      density and stone surface area (odds ratio 1.002 vs. 77.18, respectively; P<.05).
      Abdominal fat accumulation and distribution had no significant difference between
      these two groups. CONCLUSION: This study revealed that stone size, HU density,
      SSD, and stone surface area were associated with stone-free rate after ESWL
      treatment. Therefore, these factors could be used to assess the feasibility of
      ESWL before deciding the treatment strategy. Abdominal fat distribution had no
      significant impact on ESWL outcome for renal stones.

PMID- 25975633
TI  - CA-125 blood test in early detection of ovarian cancer.

PMID- 25975634
TI  - ASTRO issues new guidance for radiotherapy in NSCLC.

PMID- 25975635
TI  - Air pollution, climate change, and health.

PMID- 25975636
TI  - Bevacizumab: the phoenix of breast oncology?

PMID- 25975637
TI  - Synthesis, structure elucidation and identification of antiproliferative
      activities of a novel class of thiophene bioisosteres bearing the privileged 7,8
      dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one scaffold.
AB  - The straightforward and practical synthesis route and remarkable antitumour
      activities in vitro of a novel class of thiophene bioisosteres (10-18) are
      disclosed. These molecules were obtained with good overall yields via the
      reaction of 1-aryl-2-hydrazonoimidazolidine hydroiodides with ethyl 2-oxo-2-(2
      thienyl)acetate in the presence of triethylamine in refluxing DMF/methanol
      mixture. All the synthesized compounds proved to be markedly effective against
      human tumour cells: A549, HeLa, T47D and TOV112D and more cytotoxic than
      pemetrexed against A549, HeLa and T47D cells. Among these strongly
      antiproliferative active molecules, the disclosed three thiophene bioisosteres
      (11, 17 and 18) are proposed as the most promising anticancer lead structures for
      the rational design of more selective antitumour agents because they proved to be
      markedly lower cytotoxic towards normal than tumour cells. Results from the
      bioassay based on a double fluorochrome staining were worthy to be described
      because they provide a clue to the mode of action of one (18) of the most
      promising anticancer lead structures of the series.

PMID- 25975638
TI  - Design, synthesis and biological evaluation of bivalent benzoxazolone and
      benzothiazolone ligands as potential anti-inflammatory/analgesic agents.
AB  - Benzoxazolone and benzothiazolone were used as template blocks to develop two
      series of dimers as anti-inflammatory and analgesic agents based on the concept
      of bivalent ligands. The first series (I) involved varying the carbon chain
      lengths extending from the piperazine core to the nitrogen atom of the
      dibenzo[d]oxazol-2(3H)-one or dibenzo[d]thiazol-2(3H)-one. The second series (II)
      was designed by changing the attachment point. All compounds were screened for
      their in vitro anti-inflammatory activity in terms of the inhibition of inducible
      nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kappaB). Seventeen
      compounds inhibited both targets. Eleven of them exhibited IC50 values below 3MUM
      while five compounds showed IC50 values of 1MUM or below. Most of the compounds
      were found to be devoid of cytotoxicity against mammalian kidney and solid tumors
      cell lines up to 25MUg/mL. In vivo anti-inflammatory and antinociceptive studies
      revealed that compounds 3j, 5t and 8b have significant anti-inflammatory and
      analgesic activity comparable to that of indomethacin and ketorolac,
      respectively.

PMID- 25975639
TI  - The relationship between target-class and the physicochemical properties of
      antibacterial drugs.
AB  - The discovery of novel mechanism of action (MOA) antibacterials has been
      associated with the concept that antibacterial drugs occupy a differentiated
      region of physicochemical space compared to human-targeted drugs. With, in broad
      terms, antibacterials having higher molecular weight, lower logP and higher polar
      surface area (PSA). By analysing the physicochemical properties of about 1700
      approved drugs listed in the ChEMBL database, we show, that antibacterials for
      whose targets are riboproteins (i.e., composed of a complex of RNA and protein)
      fall outside the conventional human 'drug-like' chemical space; whereas
      antibacterials that modulate bacterial protein targets, generally comply with the
      'rule-of-five' guidelines for classical oral human drugs. Our analysis suggests a
      strong target-class association for antibacterials-either protein-targeted or
      riboprotein-targeted. There is much discussion in the literature on the failure
      of screening approaches to deliver novel antibacterial lead series, and linkage
      of this poor success rate for antibacterials with the chemical space properties
      of screening collections. Our analysis suggests that consideration of target
      class may be an underappreciated factor in antibacterial lead discovery, and that
      in fact bacterial protein-targets may well have similar binding site
      characteristics to human protein targets, and questions the assumption that
      larger, more polar compounds are a key part of successful future antibacterial
      discovery. 

PMID- 25975632
TI  - Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil,
      epirubicin, and cyclophosphamide, for women with HER2-negative early breast
      cancer (ARTemis): an open-label, randomised, phase 3 trial.
AB  - BACKGROUND: The ARTemis trial was developed to assess the efficacy and safety of
      adding bevacizumab to standard neoadjuvant chemotherapy in HER2-negative early
      breast cancer. METHODS: In this randomised, open-label, phase 3 trial, we
      enrolled women (>=18 years) with newly diagnosed HER2-negative early invasive
      breast cancer (radiological tumour size >20 mm, with or without axillary
      involvement), at 66 centres in the UK. Patients were randomly assigned via a
      central computerised minimisation procedure to three cycles of docetaxel (100
      mg/m(2) once every 21 days) followed by three cycles of fluorouracil (500
      mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) once every
      21 days (D-FEC), without or with four cycles of bevacizumab (15 mg/kg) (Bev+D
      FEC). The primary endpoint was pathological complete response, defined as the
      absence of invasive disease in the breast and axillary lymph nodes, analysed by
      intention to treat. The trial has completed and follow-up is ongoing. This trial
      is registered with EudraCT (2008-002322-11), ISRCTN (68502941), and
      ClinicalTrials.gov (NCT01093235). FINDINGS: Between May 7, 2009, and Jan 9, 2013,
      we randomly allocated 800 participants to D-FEC (n=401) and Bev+D-FEC (n=399).
      781 patients were available for the primary endpoint analysis. Significantly more
      patients in the bevacizumab group achieved a pathological complete response
      compared with those treated with chemotherapy alone: 87 (22%, 95% CI 18-27) of
      388 patients in the Bev+D-FEC group compared with 66 (17%, 13-21) of 393 patients
      in the D-FEC group (p=0.03). Grade 3 and 4 toxicities were reported at expected
      levels in both groups, although more patients had grade 4 neutropenia in the
      Bev+D-FEC group than in the D-FEC group (85 [22%] vs 68 [17%]). INTERPRETATION:
      Addition of four cycles of bevacizumab to D-FEC in HER2-negative early breast
      cancer significantly improved pathological complete response. However, whether
      the improvement in pathological complete response will lead to improved disease
      free and overall survival outcomes is unknown and will be reported after longer
      follow-up. Meta-analysis of available neoadjuvant trials is likely to be the only
      way to define subgroups of early breast cancer that would have clinically
      significant long-term benefit from bevacizumab treatment. FUNDING: Cancer
      Research UK, Roche, Sanofi-Aventis.

PMID- 25975641
TI  - Transnitrosation of non-mutagenic N-nitrosoproline forms mutagenic N-nitroso-N
      methylurea.
AB  - N-Nitroso-N-methylurea (NMU) is a potent carcinogen and suspected as a cause of
      human cancer. In this study, mutagenic NMU was detected by HPLC after the
      transnitrosation of non-mutagenic N-nitrosoproline (NP) to N-methylurea in the
      presence of thiourea (TU) under acidic conditions. The structure of NMU was
      confirmed by comparing (1)H NMR and IR spectra with that of authentic NMU after
      fractionation by column chromatography. Furthermore, a fraction containing NMU
      formed by transnitrosation was mutagenic in Salmonella typhimurium TA1535. NMU
      was formed in the reaction of NP and N-methylurea in the presence of 1,1,3,3
      tetramethylthiourea (TTU) or 1,3-dimethylthiourea in place of TU as an
      accelerator. The reaction rate constants (k) for NMU formation were correlated
      with their nucleophilicity of sulfur atom in thioureas. The N-methylurea
      concentration did not affect the NMU formation, whereas the rate of NMU formation
      correlated linearly with concentrations of NP, TTU and oxonium ion. The observed
      kinetics suggests a mechanism by which the nitroso group was transferred directly
      from the protonated NP to the thiourea then to N-methylurea to form NMU. The rate
      determining step was the formation of the complex with the protonated NP and
      thiourea.

PMID- 25975640
TI  - Structure-based design and synthesis of covalent-reversible inhibitors to
      overcome drug resistance in EGFR.
AB  - The clinical success of covalent kinase inhibitors in the treatment of EGFR
      dependent non-small cell lung cancer (NSCLC) has rejuvenated the appreciation of
      reactive small molecules. Acquired drug resistance against first-line EGFR
      inhibitors remains the major bottleneck in NSCLC and is currently addressed by
      the application of fine-tuned covalent drugs. Here we report the design,
      synthesis and biochemical evaluation of a novel class of EGFR inhibitors with a
      covalent yet reversible warhead. A series of WZ4002 analogs, derived from
      anilinopyrimidine and 3-substituted-2-cyanoacrylamide scaffolds, exhibit strong
      and selective inhibitory activity against clinically relevant EGFR(L858R) and
      EGFR(L858R/T790M).

PMID- 25975642
TI  - Synthetic 1,2,3-triazole-linked glycoconjugates bind with high affinity to human
      galectin-3.
AB  - This work describes the synthesis of the 1,2,3-triazole amino acid-derived-3-O
      galactosides 1-6 and the 1,2,3-triazole di-lactose-derived glycoconjugate 7 as
      potential galectin-3 inhibitors. The target compounds were synthesized by Cu(I)
      catalyzed azide-alkyne cycloaddition reaction ('click chemistry') between the
      azido-derived amino acids N3-ThrOBn, N3-PheOBn, N3-N-Boc-TrpOBn, N3-N-Boc-LysOBn,
      N3-O-tBu-AspOBn and N3-l-TyrOH, and the corresponding alkyne-based sugar 3-O
      propynyl-GalOMe, as well as by click chemistry reaction between the azido-lactose
      and 2-propynyl lactose. Surface plasmon resonance (SPR) assays showed that all
      synthetic glycoconjugates 1-7 bound to galectin-3 with high affinity, but the
      highest binders were the amino acids-derived glycoconjugates 2 (KD 7.96MUM) and 4
      (KD 4.56MUM), and the divalent lactoside 7 (KD1 0.15MUM/KD2 19MUM). Molecular
      modeling results were in agreement with SPR assays, since more stable
      interactions with galectin-3 were identified for glycoconjugates 2, 4 and 7.
      Regarding compounds 2 and 4, they established specific cation-pi (Arg144) and
      ionic (Asp148) interactions, whereas glycoconjugate 7 was capable to bridge two
      independent galectin-3 CRDs, creating a non-covalent cross-link between two
      monomers and, thus, reaching a submicromolar affinity towards galectin-3.

PMID- 25975643
TI  - Improving Adherence to Cancer Treatment by Addressing Quality of Life in Patients
      With Advanced Gastrointestinal Cancers.
AB  - CONTEXT: Many patients with potentially curable cancer do not complete their
      prescribed treatment regimens because of the toxicity. There is evidence that the
      common endpoints of many of these toxicities are amenable to quality of life
      (QOL)-directed interventions. OBJECTIVES: This study was conducted to determine
      the effect of a multidisciplinary QOL-directed intervention on patients'
      adherence to planned chemoradiation (CR) regimens. METHODS: The results of two
      randomized controlled trials that used the same QOL intervention were pooled to
      form a cohort of 61 patients with advanced localized gastrointestinal cancer. Of
      these 61 subjects, 29 participated in six to eight bi- to triweekly sessions that
      included exercise, education, and relaxation, and 32 received usual medical care.
      The primary endpoint was completion of their prescribed CR regimens. Secondary
      outcomes included hospitalization during CR, rates of adverse postoperative
      events, and complete pathological response in those undergoing neoadjuvant
      therapy. RESULTS: Significantly, more members of the intervention than the
      control group completed their planned CR regimens (77.8 vs. 38.2%, P = 0.003).
      More participants in the control (n = 14) than the intervention (n = 5) group (P
      = 0.063) required hospitalization. Among those undergoing neoadjuvant CR, those
      in the intervention group were significantly more likely to complete CR as
      planned (81.0% vs. 37.5%, P = 0.005) and less likely to be hospitalized (14.3%
      vs. 50.0%, P = 0.011). CONCLUSION: A structured multidisciplinary QOL-directed
      intervention delivered to patients undergoing CR may increase the proportion of
      patients who complete CR as planned and reduce unplanned hospitalizations.
      Utilization is an important outcome in QOL-directed intervention trials.

PMID- 25975644
TI  - Sensory substitution in bilateral vestibular a-reflexic patients.
AB  - Patients with bilateral vestibular loss have balance problems in darkness, but
      maintain spatial orientation rather effectively in the light. It has been
      suggested that these patients compensate for vestibular cues by relying on
      extravestibular signals, including visual and somatosensory cues, and integrating
      them with internal beliefs. How this integration comes about is unknown, but
      recent literature suggests the healthy brain remaps the various signals into a
      task-dependent reference frame, thereby weighting them according to their
      reliability. In this paper, we examined this account in six patients with
      bilateral vestibular a-reflexia, and compared them to six age-matched healthy
      controls. Subjects had to report the orientation of their body relative to a
      reference orientation or the orientation of a flashed luminous line relative to
      the gravitational vertical, by means of a two-alternative-forced-choice response.
      We tested both groups psychometrically in upright position (0 degrees ) and 90
      degrees  sideways roll tilt. Perception of body tilt was unbiased in both
      patients and controls. Response variability, which was larger for 90 degrees 
      tilt, did not differ between groups, indicating that body somatosensory cues have
      tilt-dependent uncertainty. Perception of the visual vertical was unbiased when
      upright, but showed systematic undercompensation at 90 degrees  tilt.
      Variability, which was larger for 90 degrees  tilt than upright, did not differ
      between patients and controls. Our results suggest that extravestibular signals
      substitute for vestibular input in patients' perception of spatial orientation.
      This is in line with the current status of rehabilitation programs in acute
      vestibular patients, targeting at recognizing body somatosensory signals as a
      reliable replacement for vestibular loss. 

PMID- 25975645
TI  - Neural substrates of species-dependent visual processing of faces: use of morphed
      faces.
AB  - Face identification and categorization are essential for social communication.
      The N170 event-related potential (ERP) is considered to be a biomarker of face
      perception. To elucidate the neural basis of species-dependent face processing,
      we recorded 128-ch high-density ERPs in 14 healthy adults while they viewed the
      images of morphed faces. The morphed stimuli contained different proportions of
      human and monkey faces, and the species boundary was shifted away from the center
      of the morph continuum. Three experiments were performed to determine how task
      requirement, facial orientation, and spatial frequency (SF) of visual stimuli
      affected ERPs. In an equal SF condition, the latency, and amplitude of the
      occipital P100 for upright faces were modulated in a monotonic-like fashion by
      the level of morphing. In contrast, the N170 latency for upright faces was
      modulated in a step-like fashion, showing a flexion point that may reflect
      species discrimination. Although N170 amplitudes for upright faces were not
      modulated by morph level, they were modulated in a monotonic-like fashion by
      inverted faces. The late positive (LP) component (350-550 msec) in the parietal
      region was modulated in a U-shaped function by morph level during a
      categorization task, but not in a simple reaction task. These results suggest
      that P100 reflects changes in the physical properties of faces and that N170 is
      involved in own-species selectivity. The LP component seems to represent species
      categorization that occurs 350 msec after stimulus onset. 

PMID- 25975646
TI  - The stretch-shortening cycle (SSC) revisited: residual force enhancement
      contributes to increased performance during fast SSCs of human m. adductor
      pollicis.
AB  - The stretch-shortening cycle (SSC) occurs in most everyday movements, and is
      thought to provoke a performance enhancement of the musculoskeletal system.
      However, mechanisms of this performance enhancement remain a matter of debate.
      One proposed mechanism is associated with a stretch-induced increase in steady
      state force, referred to as residual force enhancement (RFE). As yet, direct
      evidence relating RFE to increased force/work during SSCs is missing. Therefore,
      forces of electrically stimulated m. adductor pollicis (n = 14 subjects) were
      measured during and after pure stretch, pure shortening, and stretch-shortening
      contractions with varying shortening amplitudes. Active stretch (30 degrees ,
      omega = 161 +/- 6 degrees s(-1)) caused significant RFE (16%, P < 0.01), whereas
      active shortening (10 degrees , 20 degrees , and 30 degrees ; omega = 103 +/- 3
      degrees s(-1), 152 +/- 5 degrees s(-1), and 170 +/- 5 degrees s(-1)) resulted in
      significant force depression (9-15%, P < 0.01). In contrast, after SSCs (that is
      when active stretch preceded active shortening) no force depression was found.
      Indeed for our specific case in which the shortening amplitude was only 1/3 of
      the lengthening amplitude, there was a remnant RFE (10%, P < 0.01) following the
      active shortening. This result indicates that the RFE generated during
      lengthening affected force depression when active lengthening was followed by
      active shortening. As conventional explanations, such as the storage and release
      of elastic energy, cannot explain the enhanced steady-state force after SSCs, it
      appears that the stretch-induced RFE is not immediately abolished during
      shortening and contributes to the increased force and work during SSCs. 

PMID- 25975647
TI  - 5-azacytidine promotes terminal differentiation of hepatic progenitor cells.
AB  - 5-azacytidine (5-azaC) is known to induce cardiomyocyte differentiation. However,
      its function in hepatocyte differentiation is unclear. The present study
      investigated the in vitro capability of 5-azaC to promote maturation and
      differentiation of mouse embryonic hepatic progenitor cells, with the aim of
      developing an approach for improving hepatic differentiation. Mouse embryonic
      hepatic progenitor cells (HP14.5 cells) were treated with 5-azaC at
      concentrations from 0 to 20 MUmol/l, in addition to hepatocyte induction culture
      medium. Hepatocyte induction medium induces HP14.5 cell differentiation. 5-azaC
      may enhance the albumin promotor-driven Gaussia luciferase (ALB-GLuc) activity in
      induced HP14.5 cells. In the present study 2 MUmol/l was found to be the optimum
      concentration with which to achieve this. The expression of hepatocyte-associated
      factors was not significantly different between the group treated with 5-azaC
      alone and the control group. The mRNA levels of ALB; cytokeratin 18 (CK18);
      tyrosine aminotransferase (TAT); and cytochrome p450, family 1, member A1
      (CYP1A1); in addition to the protein levels of ALB, CK18 and uridine diphosphate
      glucuronyltransferase 1A (UGT1A) in the induced group with 5-azaC, were higher
      than those in the induced group without 5-azaC, although no significant
      differences were detected in expression of the hepatic stem cell markers, DLK and
      alpha-fetoprotein, between the two groups. Treatment with 5-azaC alone did not
      affect glycogen synthesis or indocyanine green (ICG) metabolic function in HP14.5
      cells, although it significantly increased ICG uptake and periodic acid-Schiff
      positive cell numbers amongst HP14.5 cells. Therefore, the present study
      demonstrated that treatment with 5-azaC alone exerted no effects on the
      maturation and differentiation of HP14.5 cells. However, 5-azaC exhibited a
      synergistic effect on the terminal differentiation of induced hepatic progenitor
      cells in association with a hepatic induction medium.

PMID- 25975648
TI  - Long-term, low-dose tigecycline to treat relapsing bloodstream infection due to
      KPC-producing Klebsiella pneumoniae after major hepatic surgery.
AB  - A 68-year-old male underwent a right hepatectomy, resection of the biliary
      convergence, and a left hepatic jejunostomy for a Klatskin tumour. The
      postoperative course was complicated by biliary abscesses with relapsing
      bloodstream infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing
      Klebsiella pneumoniae (KPC-Kp). A 2-week course of combination antibiotic therapy
      failed to provide source control and the bacteraemia relapsed. Success was
      obtained with a regimen of tigecycline 100mg daily for 2 months, followed by
      tigecycline 50mg daily for 6 months, then 50mg every 48h for 3 months. No side
      effects were reported. 

PMID- 25975649
TI  - Severe human parechovirus type 3 myocarditis and encephalitis in an adolescent
      with hypogammaglobulinemia.
AB  - Human parechovirus (HPeV) belongs to the Picornaviridae family of RNA viruses.
      HPeV infections can be asymptomatic, lead to mild respiratory and/or
      gastrointestinal symptoms, or less frequently cause severe diseases such as
      sepsis, meningitis, encephalitis, and myocarditis. Severe neurological HPeV
      infections occur most commonly in infants and neonates. There are currently 16
      recognized types of HPeV. HPeV type 3 (HPeV3) has been the predominant type
      associated with severe central nervous system disease in neonates and newborns
      since its discovery in 1999. Although HPeV-related infections have been reported
      in adults, symptomatic HPeV3 infections in adolescents and adults are uncommon. A
      case of severe HPeV3 myocarditis and encephalitis in an adolescent is described. 

PMID- 25975650
TI  - Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and
      laboratory findings.
AB  - A 6-year-old boy from India developed an atypical form of rabies following a
      stray dog bite and as a consequence of not receiving the standard World Health
      Organization recommended post-exposure prophylaxis for category III wounds.
      Serial rising rabies virus neutralizing antibody titres in serum and
      cerebrospinal fluid by rapid fluorescent focus inhibition test helped confirm the
      diagnosis of rabies. The child has survived for 4 months since the onset of
      illness, albeit with neurological sequelae. 

PMID- 25975651
TI  - Human melioidosis reported by ProMED.
AB  - OBJECTIVE: There are limited sources describing the global burden of emerging
      diseases. A review of human melioidosis reported by ProMED was performed and the
      reliability of the data retrieved assessed in comparison to published reports.
      The effectiveness of ProMED was evaluated as a source of epidemiological data by
      focusing on melioidosis. METHODS: Using the keyword 'melioidosis' in the ProMED
      search engine, all of the information from the reports and collected data was
      reviewed using a structured form, including the year, country, gender,
      occupation, number of infected individuals, and number of fatal cases. RESULTS:
      One hundred and twenty-four entries reported between January 1995 and October
      2014 were identified. A total of 4630 cases were reported, with death reported in
      505 cases, suggesting a misleadingly low overall case fatality rate (CFR) of 11%.
      Of 20 cases for which the gender was reported, 12 (60%) were male. Most of the
      cases were reported from Australia, Thailand, Singapore, Vietnam, and Malaysia,
      with sporadic reports from other countries. CONCLUSIONS: Internet-based reporting
      systems such as ProMED are useful to gather information and synthesize knowledge
      on emerging infections. Although certain areas need to be improved, ProMED
      provided good information about melioidosis.

PMID- 25975652
TI  - Evaluation of spa-typing of methicillin-resistant Staphylococcus aureus using
      high-resolution melting analysis.
AB  - OBJECTIVE: spa-typing of methicillin-resistant Staphylococcus aureus (MRSA) has
      been used widely in clinical diagnostics and epidemiological studies. The aim of
      this study was to evaluate high-resolution melting (HRM) as a rapid and cost
      effective method, to replace DNA-sequencing, for spa-typing in a global
      collection of 50 MRSA isolates. METHODS: The polymorphic X region of the spa gene
      was amplified by colony PCR using the SensiMix HRM kit, and the melting
      temperature (Tm) and melting curves of the amplicons were analyzed in close tubes
      using a Rotor-Gene 6000 instrument. RESULTS: Fifteen out of 19 spa-types each had
      a distinct Tm, which was sufficient to unambiguously type each of these spa
      types. The remaining four spa-types could not be separated by Tm alone: t008 and
      t2770 shared a Tm (80.3 degrees C) and t021 and t311 shared a Tm (80.0 degrees
      C). However, they could be separated based on the shapes of their melting curves.
      There are discrepancies between the findings of the present study and those of
      previous studies, suggesting that standardization remains a challenge for cross
      referencing. CONCLUSION: HRM-based spa-typing is reproducible, simple, rapid, and
      cost-effective. t037 is prevalent in Brazil and Sudan, while diverse spa-types
      are found in Scotland and Saudi Arabia. Standardization is required for cross
      referencing between laboratories globally.

PMID- 25975653
TI  - Red Flags for Necrotizing Fasciitis: A Case Control Study.
AB  - OBJECTIVE: to examine the diagnostic accuracy of traditional 'red flags' for
      necrotizing fasciitis (NF) on history and physical examination. METHODS:
      retrospective study of all cases of NF admitted to a large tertiary care hospital
      between January 1 2004 and December 31 2013, each matched to two control patients
      with cellulitis. We determined the diagnostic test characteristics of clinical
      features for distinguishing NF from cellulitis, with emphasis on positive (LR+)
      and negative (LR-) likelihood ratios. RESULTS: There were no individual findings
      with sufficient sensitivity to rule out NF (sensitivity <= 85% and LR- >= 0.5 for
      all findings). The clinical features that most significantly increased the odds
      of NF were recent surgery (LR+ 7.0) pain-out-of-proportion (LR+ 4.5), diarrhea
      (LR+ 6.0), hypotension (LR+ 8.0), altered mental status (LR+ 3.3), erythema
      progressing beyond margins (LR+3.1), fluctuance (LR+ 5.0), hemorrhagic bullae
      (LR+ 8.0) and skin necrosis (LR+ 30.0). Each individual finding conferred low
      sensitivity, but absence of all nine ruled out NF (LR- 0.04). The presence of >=3
      findings ruled in NF (LR+ undefined). CONCLUSIONS: When considered together, the
      traditional 'red flags' for NF may be sufficient to rule in or rule out the
      diagnosis. If future prospective studies validate these findings, there will be a
      potential opportunity to expedite NF diagnosis and improve patient outcomes.

PMID- 25975654
TI  - A case of non-O1/non-O139 Vibrio cholerae septicemia and meningitis in a neonate.
AB  - A case of septicemia with meningitis due to non-O1/non-O139 Vibrio cholerae in a
      neonate is reported. The genotype and phenotype of the isolate were examined in
      relation to the major virulence genes. The isolate was shown to be non-toxin but
      cytotoxin-producing, distinguished from the dominant clone of non-O1/non-O139V.
      cholerae by multilocus sequence typing. 

PMID- 25975655
TI  - Linezolid-induced complex partial seizure in a patient without epilepsy.

PMID- 25975656
TI  - Drug Discovery of Therapies for Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by
      the loss of the muscle protein, dystrophin, leading to progressive loss of muscle
      fibers and muscle weakness. Drug discovery efforts targeting DMD have used two
      main approaches: (1) the restoration of dystrophin expression or the expression
      of a compensatory protein, and (2) the mitigation of downstream pathological
      mechanisms, including dysregulated calcium homeostasis, oxidative stress,
      inflammation, fibrosis, and muscle ischemia. The aim of this review is to
      introduce the disease, its pathophysiology, and the available research tools to a
      drug discovery audience. This review will also detail the most promising
      therapies that are currently being tested in clinical trials or in advanced
      preclinical models. 

PMID- 25975657
TI  - The sympathetic/parasympathetic imbalance in heart failure with reduced ejection
      fraction.
AB  - Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure,
      has adverse implications for symptoms during wakefulness and sleep; for cardiac,
      renal, and immune function; for exercise capacity; and for lifespan and mode of
      death. The objectives of this Clinical Review are to summarize current knowledge
      concerning mechanisms for disturbed parasympathetic and sympathetic circulatory
      control in heart failure with reduced ejection fraction and its clinical and
      prognostic implications; to demonstrate the patient-specific nature of
      abnormalities underlying this common phenotype; and to illustrate how such
      variation provides opportunities to improve or restore normal
      sympathetic/parasympathetic balance through personalized drug or device therapy. 

PMID- 25975658
TI  - The perils of surrogate endpoints.

PMID- 25975660
TI  - miR-21 and cardiac fibrosis: another brick in the wall?

PMID- 25975659
TI  - Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter
      ablation in non-valvular atrial fibrillation.
AB  - AIMS: VENTURE-AF is the first prospective randomized trial of uninterrupted
      rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial
      fibrillation (NVAF) undergoing catheter ablation (CA). METHODS AND RESULTS: Trial
      size was administratively set at 250, the protocol-specified target. Events were
      independently and blindly adjudicated. We randomly assigned 248 NVAF patients to
      uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to
      CA and for 4 weeks afterwards. The primary endpoint was major bleeding events
      after CA. Secondary endpoints included thromboembolic events (composite of
      stroke, systemic embolism, myocardial infarction, and vascular death) and other
      bleeding or procedure-attributable events. Patients were 59.5 +/- 10 years of
      age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The
      average total heparin dose used to manage activated clotting time (ACT) was
      slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level
      attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms,
      respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding
      event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1
      vascular death). All events occurred in the VKA arm and all after CA. The number
      of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any
      other procedure-attributable events (5 vs. 5) were similar. CONCLUSION: In
      patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was
      feasible and event rates were similar to those for uninterrupted VKA therapy.
      NAME OF THE TRIAL REGISTRY: Clinicaltrials.gov trial registration number is
      NCT01729871.

PMID- 25975661
TI  - Deep developmental transcriptome sequencing uncovers numerous new genes and
      enhances gene annotation in the sponge Amphimedon queenslandica.
AB  - BACKGROUND: The demosponge Amphimedon queenslandica is amongst the few early
      branching metazoans with an assembled and annotated draft genome, making it an
      important species in the study of the origin and early evolution of animals.
      Current gene models in this species are largely based on in silico predictions
      and low coverage expressed sequence tag (EST) evidence. RESULTS: Amphimedon
      queenslandica protein-coding gene models are improved using deep RNA-Seq data
      from four developmental stages and CEL-Seq data from 82 developmental samples.
      Over 86% of previously predicted genes are retained in the new gene models,
      although 24% have additional exons; there is also a marked increase in the total
      number of annotated 3' and 5' untranslated regions (UTRs). Importantly, these new
      developmental transcriptome data reveal numerous previously unannotated protein
      coding genes in the Amphimedon genome, increasing the total gene number by 25%,
      from 30,060 to 40,122. In general, Amphimedon genes have introns that are
      markedly smaller than those in other animals and most of the alternatively
      spliced genes in Amphimedon undergo intron-retention; exon-skipping is the least
      common mode of alternative splicing. Finally, in addition to canonical
      polyadenylation signal sequences, Amphimedon genes are enriched in a number of
      unique AT-rich motifs in their 3' UTRs. CONCLUSIONS: The inclusion of
      developmental transcriptome data has substantially improved the structure and
      composition of protein-coding gene models in Amphimedon queenslandica, providing
      a more accurate and comprehensive set of genes for functional and comparative
      studies. These improvements reveal the Amphimedon genome is comprised of a
      remarkably high number of tightly packed genes. These genes have small introns
      and there is pervasive intron retention amongst alternatively spliced
      transcripts. These aspects of the sponge genome are more similar unicellular
      opisthokont genomes than to other animal genomes.

PMID- 25975662
TI  - Differential effects of bevacizumab, ranibizumab and aflibercept on cell
      viability, phagocytosis and mitochondrial bioenergetics of retinal pigment
      epithelial cell.
AB  - PURPOSE: To evaluate the short- and long-term effects of most clinically used
      anti-vascular endothelial growth factor agents, including bevacizumab,
      ranibizumab or aflibercept, on cell viability, phagocytosis, mitochondrial
      bioenergetics and the oxidant acrolein-induced oxidative stress of human adult
      retinal pigment epithelial (ARPE)-19 cells. METHODS: In cultured ARPE-19 cells,
      cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay, phagocytotic activity and intracellular reactive
      oxygen species (ROS) level were determined by flow cytometry, mitochondrial
      bioenergetics was assessed using a Seahorse XF24 Extracellular Flux Analyzer, and
      protein expression was measured by Western blotting. RESULTS: Long-term exposure
      to all three agents had no effect on cell viability; but rescued the ARPE-19
      cells from acrolein-induced decrease in cell viability. Bevacizumab, but not
      ranibizumab or aflibercept, suppressed the phagocytotic activity of ARPE-19 cells
      and exerted significantly less protection against acrolein-induced inhibition of
      phagocytosis. Both ranibizumab and aflibercept increased basal respiratory rate
      and maximal mitochondrial respiratory capacity after 1-hr exposure; but returned
      to baseline following 24- or 72-hr exposure. In contrast, both responses were
      reduced on short-term exposure, but augmented after long-term exposure to
      bevacizumab. Long-term pretreatment with all three agents reversed acrolein
      induced impairment of mitochondrial bioenergetics, overproduction of ROS and
      phosphorylation of the mitogen-activated protein kinases in ARPE-19 cells.
      CONCLUSION: Bevacizumab might affect mitochondrial bioenergetics differently from
      that by ranibizumab and aflibercept. Ranibizumab and aflibercept at their
      therapeutic dose protect against acrolein-induced oxidative cytotoxicity in human
      ARPE-19 cells via an increase in mitochondrial bioenergetics. An early protective
      action on mitochondrial bioenergetic capacity might be used to predict possible
      long-term antioxidative effects of the agents in the eye.

PMID- 25975663
TI  - Topological effects of network structure on long-term social network dynamics in
      a wild mammal.
AB  - Social structure influences ecological processes such as dispersal and invasion,
      and affects survival and reproductive success. Recent studies have used static
      snapshots of social networks, thus neglecting their temporal dynamics, and
      focused primarily on a limited number of variables that might be affecting social
      structure. Here, instead we modelled effects of multiple predictors of social
      network dynamics in the spotted hyena, using observational data collected during
      20 years of continuous field research in Kenya. We tested the hypothesis that the
      current state of the social network affects its long-term dynamics. We employed
      stochastic agent-based models that allowed us to estimate the contribution of
      multiple factors to network changes. After controlling for environmental and
      individual effects, we found that network density and individual centrality
      affected network dynamics, but that social bond transitivity consistently had the
      strongest effects. Our results emphasise the significance of structural
      properties of networks in shaping social dynamics.

PMID- 25975664
TI  - Non-inferiority of nitric oxide releasing intranasal spray compared to sub
      therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine
      respiratory disease complex in low to moderate risk beef cattle arriving at a
      commercial feedlot.
AB  - Undifferentiated fever, or bovine respiratory disease complex (BRDc), is a
      challenging multi-factorial health issue caused by viral/bacterial pathogens and
      stressors linked to the transport and mixing of cattle, negatively impacting the
      cattle feedlot industry. Common practice during processing at feedlots is
      administration of antibiotic metaphylaxis to reduce the incidence of BRDc. Nitric
      oxide (NO) is a naturally occurring nano-molecule with a wide range of
      physiological attributes. This study evaluated the metaphylactic use of
      intranasal NO releasing spray (NORS) to control BRDc incidence in calves at low
      moderate risk of developing BRDc, arriving at a commercial feedlot as compared to
      conventional antibiotic metaphylaxis. One thousand and eighty crossbred, multiple
      sourced, commingled, commercial, weaned beef calves were screened, enrolled,
      randomized and treated upon arrival. Animals appearing sick were pulled (from
      their pen) by blinded pen keepers then assessed for BRDc symptoms; blood samples
      were taken for haptoglobin quantification and the animals were rescued with an
      antibiotic. After 35 days both groups showed no significant difference in BRDc
      incidence (5.2% of animals from NORS group and 3.2% from antibiotic group).
      Average daily weight gain of animals at day 150 for the NORS cohort was 1.17kg
      compared to 1.18kg for the antibiotic group (p>0.05). There was no significant
      difference in mortality in the first 35 days (p=0.7552), however, general
      mortality over 150 days trended higher in the antibiotic cohort. NORS treatment
      was shown to be safe, causing neither distress nor adverse effects on the
      animals. This large randomized controlled study in low-moderate BRDc incidence
      risk calves demonstrates that NORS treatment, as compared to conventional
      metaphylactic antibiotics, is non-inferior based on BRDc incidence and other
      metrics like weight and mortality. These data justify further studies in higher
      BRDc incidence risk populations to evaluate NORS as an alternative strategy to
      reduce sub-therapeutic metaphylaxis antibiotic use in beef cattle production.

PMID- 25975666
TI  - Influence of the retention of PI calves identified in 2012 during the voluntary
      phase of the Irish national bovine viral diarrhoea virus (BVDV) eradication
      programme on herd-level outcomes in 2013.
AB  - This study was undertaken to investigate the impact of the retention of calves
      born in one calving season and considered to be persistently infected (PI) with
      bovine viral diarrhoea virus (BVDV) on herd-level outcomes in the following
      calving season. A secondary aim was to investigate the relationship between
      retention and the number of BVD+ calves detected the following season. The study
      population included a subset of herds enrolled in the 2012 voluntary BVD
      eradication programme in Ireland, specifically those with a birth registered to
      more than 80% of the cows between 1st January and 15th July and BVDV test results
      available for at least 80% of these calves, during both 2012 and 2013. Calves
      were considered PI based on either an initial positive result without further
      testing (BVDPOS) or a positive result on confirmatory testing (BVDPI),
      collectively considered BVD+ calves. Herd-level outcomes included the BVD status
      of the herd, and the number of BVD+ calves born between 1st January and 15th July
      2013 (the study period). There was a significant univariable association between
      herd BVD status in 2013 and a number of general herd factors, including location,
      herd type, size and number of introduced animals (overall and those pregnant at
      time of introduction), as well as with each of six different factors related to
      the retention of virus-positive calves: the number of BVD+ calves in 2012; the
      maximum time (days) any one BVD+ born in 2012 was retained up to September 2013;
      the mean time (days) BVD+ animal(s) born in 2012 were retained up to September
      2013; the date (quarter/year) the last BVD+ left the herd; the presence/number of
      2012-born BVD+ retained in the herd at 1st January 2013. Separate multivariable
      models were constructed for each retention variable. The best model fit (based on
      AIC) was obtained using the retention variable "date (quarter/year) last BVD+
      calf left the herd", followed by "total time all BVD+ calves were retained in the
      herd", with (log) herd size also retained in the models. Significant differences
      were also found in the number of positive calves detected in positive herds in
      2013 for all of the calf retention risk factors. These findings confirm an
      increased probability of finding a BVD+ animal in a herd following the retention
      of positive calves born in the previous calving season, highlighting the
      importance of their prompt removal. 

PMID- 25975665
TI  - Clinical utility and performance of sock sampling in weaner pig diarrhoea.
AB  - Low pathogen diarrhoea is a group-level diagnosis, characterised by non
      haemorrhagic diarrhoea. In the current study, the apparent prevalence of low
      pathogen diarrhoea outbreaks in Danish herds was investigated along with the
      clinical utility of a laboratory examination for intestinal disease, agreement
      between three consecutive herd examinations from the same herd and agreement
      between quantitative PCR results from pooled faecal samples and sock samples.
      Twenty-four veterinarians submitted faecal and sock samples for quantitative PCR
      testing from outbreaks of diarrhoea in nursery pigs (n=38 herds) where the farmer
      or veterinarian had decided that antimicrobial treatment was necessary. The
      veterinarians were asked to fill in a questionnaire and participate in telephone
      interviews. The apparent prevalence of low pathogen diarrhoea was 0.18 (95% CL:
      0.08-0.34). Agreement between the veterinarians' clinical aetiological diagnosis
      and the pooled faecal sample was 0.18 (95% CL: 0.08-0.34), and Cohen's Kappa was
      0.03 (95% CL: -0.08 to 0.14). Antibiotic treatment or prevention strategies were
      changed in 0.63 (95% CL: 0.46-0.78) of the herds, and the veterinarians indicated
      that, for 0.32 (95% CL: 0.18-0.50) of the herds, changes were related to the
      diagnostic results from the laboratory examination performed in the study. In
      0.16 (95% CL: 0.05-0.36) of the herds, the same infections were demonstrated at
      all three consecutive examinations. No herds had three consecutive diarrhoea
      outbreaks classified as low pathogen diarrhoea. For the quantitative results
      (log10 of the summed amounts of Lawsonia intracellularis, Brachyspira pilosicoli,
      Escherichia coli F4 and F18) agreement between pooled faecal samples and sock
      samples was evaluated. Lin's concordance correlation coefficient was 0.69 (95%
      CL: 0.48-0.82), and the mean difference between the two types of samples was 
      0.38 log10 bacteria/g faeces (SD=1.59log10 bacteria/g faeces; 95% CI: -0.90 to
      0.14log10 bacteria/g faeces). Agreement for the dichotomised results was 0.89
      (95% CI: 0.75-0.97) when test results were classified as low pathogen diarrhoea
      or not, and Cohen's Kappa was 0.61 (95% CI: 0.26-0.95). In relation to detection
      of the individual infections, agreement was 0.63 (95% CI: 0.46-0.78), and Cohen's
      Kappa was 0.53 (95% CI: 0.34-0.71). In conclusion, low pathogen diarrhoea is a
      common finding amongst diarrhoea outbreaks that are subjected to antibiotic batch
      treatment in Danish nursery pigs. Sock samples seem to offer a reliable
      diagnostic method with impact on clinical decisions for treatment and prevention.
      However, both the diarrhoea type and the aetiology change with time in the
      majority of herds, indicating a potential need for frequent diagnostic
      examinations. 

PMID- 25975667
TI  - Reply: Increased mortality for pregnancy-associated melanoma: systematic review
      and meta-analysis.

PMID- 25975668
TI  - The tegumental surface membranes of Schistosoma mansoni are enriched in parasite
      specific phospholipid species.
AB  - The complex surface structure of adult Schistosoma mansoni, the tegument, is
      essential for survival of the parasite. This tegument is syncytial and is covered
      by two closely-apposed lipid bilayers that form the interactive surface with the
      host. In order to identify parasite-specific phospholipids present in the
      tegument, the species compositions of the major glycerophospholipid classes,
      phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and
      phosphatidylinositol, including lysophospholipid species, were analysed in adult
      S. mansoni worms, isolated tegumental membranes and hamster blood cells. It was
      shown that there are large differences in species composition in all four
      phospholipid classes between the membranes of S. mansoni and those of the host
      blood cells. The species compositions of phosphatidylserine and
      phosphatidylcholine were strikingly different in the tegument compared with the
      whole worm. The tegumental membranes are especially enriched in
      lysophospholipids, predominantly eicosenoic acid (20:1)-containing lyso
      phosphatidylserine and lyso-phosphatidylethanolamine species. Furthermore, the
      tegument was strongly enriched in phosphatidylcholine that contained 5
      octadecenoic acid, an unusual fatty acid that is not present in the host. As we
      have shown previously that lysophospholipids from schistosomes affect the
      parasite-host interaction, excretion of these tegument-specific phospholipid
      species was examined in vitro and in vivo. Our experiments demonstrated that
      these lysophospholipids are not significantly secreted during in vitro
      incubations and are not detectable in peripheral blood of infected hosts.
      However, these analyses demonstrated a substantial decrease in PI content of
      blood plasma from schistosome-infected hamsters, which might indicate that
      schistosomes influence exosome formation by the host. 

PMID- 25975669
TI  - Complex role of Kv7 channels in cGMP and cAMP-mediated relaxations.

PMID- 25975670
TI  - Evaluation of articulation simulation system using artificial maxillectomy
      models.
AB  - Acoustic evaluation is valuable for guiding the treatment of maxillofacial
      defects and determining the effectiveness of rehabilitation with an obturator
      prosthesis. Model simulations are important in terms of pre-surgical planning and
      pre- and post-operative speech function. This study aimed to evaluate the
      acoustic characteristics of voice generated by an articulation simulation system
      using a vocal tract model with or without artificial maxillectomy defects. More
      specifically, we aimed to establish a speech simulation system for maxillectomy
      defect models that both surgeons and maxillofacial prosthodontists can use in
      guiding treatment planning. Artificially simulated maxillectomy defects were
      prepared according to Aramany's classification (Classes I-VI) in a three
      dimensional vocal tract plaster model of a subject uttering the vowel /a/.
      Formant and nasalance acoustic data were analysed using Computerized Speech Lab
      and the Nasometer, respectively. Formants and nasalance of simulated /a/ sounds
      were successfully detected and analysed. Values of Formants 1 and 2 for the non
      defect model were 675.43 and 976.64 Hz, respectively. Median values of Formants 1
      and 2 for the defect models were 634.36 and 1026.84 Hz, respectively. Nasalance
      was 11% in the non-defect model, whereas median nasalance was 28% in the defect
      models. The results suggest that an articulation simulation system can be used to
      help surgeons and maxillofacial prosthodontists to plan post-surgical defects
      that will be facilitate maxillofacial rehabilitation.

PMID- 25975671
TI  - Health in All Policies: A cross-sectional study of the public health
      coordinators' role in Norwegian municipalities.
AB  - AIMS: The public health coordinator (PHC) is a municipal-government position in
      Norway whose role is to organise and oversee municipal policies and functions to
      support national public health goals. This cross-sectional study investigates
      conditions associated with use of PHCs by Norwegian municipalities in the period
      immediately before the new Public Health Act came into effect in 2012,
      decentralising responsibility for citizen health to the municipal level. This
      study provides descriptive baseline data regarding Norwegian municipalities' use
      of PHCs in this time - a marker for municipal engagement with inter-sectorial
      collaboration - before this policy was nationally mandated, and explores whether
      municipal characteristics such as structure, socio-economic status and extent of
      Health in All Policies (HiAP) implementation were associated factors. METHODS:
      All Norway's municipalities (N=428) were included. We combined Norwegian register
      data with survey data. Descriptive analyses and bi- and multivariate logistic
      regression analyses were performed. RESULTS: A total of 76% of Norwegian
      municipalities employed a PHC in the period just before 2012. Of the PHCs
      employed, 22% were employed full time and 28% were located within the staff of
      the chief executive office. Our study indicates that partnership for health
      promotion with county councils (OR=7.78), development of a health overview
      (OR=3.53), collaboration with non-government sectors (OR=2.85) and low socio
      economic status (OR=0.46) are significantly associated with Norwegian
      municipalities having a PHC. CONCLUSIONS: This study suggests that the
      municipality's implementation of HiAP, as well as lower socio-economic
      indicators, is associated with the use of PHCs in Norway, but not factors related
      to municipal structure.

PMID- 25975672
TI  - The promise of non-invasive prenatal testing needs to be monitored
      scientifically.

PMID- 25975673
TI  - Abstracts of the MASCC/ISOO 2015 Annual Meeting [corrected].

PMID- 25975674
TI  - Response.

PMID- 25975675
TI  - Physical activity levels of overweight or obese breast cancer survivors:
      correlates at entry into a weight loss intervention study.
AB  - PURPOSE: Physical activity is associated with reduced risk and progression of
      breast cancer, and exercise can improve physical function, quality of life, and
      fatigue in cancer survivors. Evidence on factors associated with cancer
      survivors' adherence to physical activity guidelines from the American Cancer
      Society and the U.S. Department of Health and Human Services is mixed. This study
      seeks to help fill this gap in knowledge by examining correlates with physical
      activity among breast cancer survivors. METHODS: Overweight or obese breast
      cancer survivors (N = 692) were examined at enrollment into a weight loss
      intervention study. Questionnaires and medical record review ascertained data on
      education, race, ethnicity, menopausal status, physical activity, and medical
      history. Measures of anthropometrics and fitness level were conducted. Regression
      analysis examined associations between physical activity and demographic,
      clinical, and lifestyle factors. RESULTS: Overall, 23% of women met current
      guidelines. Multivariate analysis revealed that body mass index (p = 0.03),
      emergency room visits in the past year (p = 0.04), and number of comorbidities (p
      = 0.02) were associated with less physical activity. Geographic region also was
      associated with level of physical activity (p = 0.02), with women in Alabama
      reporting significantly less activity than those in other participating regions.
      CONCLUSIONS: The majority of overweight/obese breast cancer survivors did not
      meet physical activity recommendations. Physical activity levels were associated
      with degree of adiposity, geographic location, and number of comorbidities. The
      majority of overweight breast cancer survivors should be encouraged to increase
      their level of physical activity. Individualizing exercise prescriptions
      according to medical comorbidities may improve adherence.

PMID- 25975677
TI  - Hypofractionated palliative radiotherapy for bladder cancer.
AB  - PURPOSE: The aim of this study was to evaluate hematuria-free survival as well as
      acute and late toxicity after hypofractionated palliative radiotherapy for
      bladder cancer. METHODS AND MATERIALS: Between September 2004 and January 2013,
      44 patients with biopsy-proven urothelial carcinoma of the bladder were
      irradiated according to a palliative schedule to a total dose of 34.5 Gy in six
      fractions of 5.75 Gy given once a week. RESULTS: After a mean follow-up of 10
      months, 91% of patients were still hematuria free, with a mean hematuria-free
      survival of 13 months. Severe (>= grade 3) acute and late urinary toxicity was
      observed in 9 and 19% of patients, respectively. CONCLUSION: This
      hypofractionated radiotherapy schedule appears to result in acceptable toxicity
      and manages successful and long-term palliation of hematuria in most patients.

PMID- 25975678
TI  - YY v TURKEY: INFERTILITY AS A PRE-CONDITION FOR GENDER CONFIRMATION SURGERY.
AB  - In YY v Turkey, the Second Chamber of the European Court of Human Rights (ECtHR)
      held that Turkey's refusal, over a period of many years, to authorise gender
      confirmation surgery because the applicant remained capable of procreating was a
      violation of the right to private life under Art. 8 of the European Convention on
      Human Rights. The Second Chamber's judgment acknowledges, and gives practical
      effect to, the 'physical and moral security' of transgender persons. YY has the
      potential to revolutionise gender confirming health care in Europe and will
      hopefully ensure that, where individuals do seek to medically transition, they
      need only access to treatments that are both necessary and desired. The ECtHR's
      decision may also impact upon the legal recognition of transgender identities.
      While not the direct focus of the Second Chamber's assessment, legal gender
      recognition is a constant theme throughout the judgment, and many of the Court's
      arguments are equally applicable to legal schemes for acknowledging preferred
      gender. 

PMID- 25975676
TI  - The biology of cancer-related fatigue: a review of the literature.
AB  - PURPOSE: Understanding the etiology of cancer-related fatigue (CRF) is critical
      to identify targets to develop therapies to reduce CRF burden. The goal of this
      systematic review was to expand on the initial work by the National Cancer
      Institute CRF Working Group to understand the state of the science related to the
      biology of CRF and, specifically, to evaluate studies that examined the
      relationships between biomarkers and CRF and to develop an etiologic model of CRF
      to guide researchers on pathways to explore or therapeutic targets to
      investigate. METHODS: This review was completed by the Multinational Association
      of Supportive Care in Cancer Fatigue Study Group-Biomarker Working Group. The
      initial search used three terms (biomarkers, fatigue, cancer), which yielded
      11,129 articles. After removing duplicates, 9145 articles remained. Titles were
      assessed for the keywords "cancer" and "fatigue" resulting in 3811 articles.
      Articles published before 2010 and those with samples <50 were excluded, leaving
      75 articles for full-text review. Of the 75 articles, 28 were further excluded
      for not investigating the associations of biomarkers and CRF. RESULTS: Of the 47
      articles reviewed, 25 were cross-sectional and 22 were longitudinal studies. More
      than half (about 70 %) were published recently (2010-2013). Almost half (45 %)
      enrolled breast cancer participants. The majority of studies assessed fatigue
      using self-report questionnaires, and only two studies used clinical parameters
      to measure fatigue. CONCLUSIONS: The findings from this review suggest that CRF
      is linked to immune/inflammatory, metabolic, neuroendocrine, and genetic
      biomarkers. We also identified gaps in knowledge and made recommendations for
      future research.

PMID- 25975680
TI  - Finding the New Normal: Accepting Changes After Combat-Related Mild Traumatic
      Brain Injury.
AB  - INTRODUCTION: More than 300,000 soldiers have returned from Southwest Asia (i.e.,
      Iraq and Afghanistan) with combat-related mild traumatic brain injuries (mTBIs).
      Despite less visible physical injuries, these soldiers demonstrate various
      physical and cognitive symptoms that impact their ability to reintegrate post
      mTBI. This study explores family reintegration experiences, as described by
      married dyads, following a combat-related mTBI. METHODS: Nine soldiers with mTBI
      and their spouses participated, and a total of 27 interviews, both joint and
      individual, were conducted. Strauss and Corbin's grounded theory methodology and
      semistructured interviews were used to collect participants' perceptions and
      analyze the data. FINDINGS: The overarching theme of the reintegration experience
      is described as finding the "new normal." A new normal was defined by
      participants as the couple's new, post-mTBI expectation of the family unit or
      family routine. Some participants indicated that they had accepted the post-mTBI
      changes and were working toward this new normal, whereas others indicated these
      changes were unacceptable and continued their efforts to return to pre-injury
      functioning. CONCLUSIONS: Individuals with mTBI and their families may benefit
      from interventions that directly address mismatched expectations and promote the
      acceptance of a new normal.

PMID- 25975681
TI  - [Advances in research of metabolomics in cancer diagnosis].

PMID- 25975679
TI  - Melatonin reverses H2 O2 -induced premature senescence in mesenchymal stem cells
      via the SIRT1-dependent pathway.
AB  - Mesenchymal stem cells (MSCs) represent an attractive source for stem cell-based
      regenerative therapy, but they are vulnerable to oxidative stress-induced
      premature senescence in pathological conditions. We previously reported
      antioxidant and antiarthritic effects of melatonin on MSCs against
      proinflammatory cytokines. In this study, we hypothesized that melatonin could
      protect MSCs from premature senescence induced by hydrogen peroxide (H2 O2 ) via
      the silent information regulator type 1 (SIRT1)-dependent pathway. In response to
      H2 O2 at a sublethal concentration of 200 MUm, human bone marrow-derived MSCs (BM
      MSCs) underwent growth arrest and cellular senescence. Treatment with melatonin
      before H2 O2 exposure cannot significantly prevent premature senescence; however,
      treatment with melatonin subsequent to H2 O2 exposure successfully reversed the
      senescent phenotypes of BM-MSCs in a dose-dependent manner. This result was made
      evident by improved cell proliferation, decreased senescence-associated beta
      galactosidase activity, and the improved entry of proliferating cells into the S
      phase. In addition, treatment with 100 MUm melatonin restored the osteogenic
      differentiation potential of BM-MSCs that was inhibited by H2 O2 -induced
      premature senescence. We also found that melatonin attenuated the H2 O2 
      stimulated phosphorylation of p38 mitogen-activated protein kinase, decreased
      expression of the senescence-associated protein p16(INK) (4alpha) , and increased
      SIRT1. Further molecular experiments revealed that luzindole, a nonselective
      antagonist of melatonin receptors, blocked melatonin-mediated antisenescence
      effects. Inhibition of SIRT1 by sirtinol counteracted the protective effects of
      melatonin, suggesting that melatonin reversed the senescence in cells through the
      SIRT1-dependent pathway. Together, these findings lay new ground for
      understanding oxidative stress-induced premature senescence and open perspectives
      for therapeutic applications of melatonin in stem cell-based regenerative
      medicine.

PMID- 25975682
TI  - [Establishment of a new human glioma cell line and analysis of its biological
      characteristics].
AB  - OBJECTIVE: To establish a new glioma cell line and analyze its biological
      characteristics, and to provide a useful cellular tool with new features for
      cancer research. METHODS: Glioma tissue was taken from surgical specimen clinical
      of a clinical patient. Primary culture was carried out, and a cell line (SHG139)
      was established after 10 passages. Immunofluorescence staining was performed to
      detect the expression of proteins, and cell proliferation and cycle were detected
      by flow cytometry method (FCM). The biological characteristics of SHG139 cells
      were detected by chromosome karyotype analysis. SHG139s glioma cells derived from
      SHG139 glioma cell line were cultured with neural stem cell medium. Then stem
      cell markers were determined. SHG139s cells were induced with serum-containing
      medium, and their expression of A2B5, GFAP, beta-III tubulin, and GalC was
      detected. Intracranial xenograft tumor of both SHG139 glioma cells and SHG139s
      glioma stem cell spheres was generated in rats. RESULTS: The expressions of A2B5,
      GalC, GFAP, S-100, and vimentin in the 20 and 60 passages of SHG139 cells were
      positive, consistent with the immunohistochemical results and pathological
      features. SHG139 cells proliferated significantly within 24 h after subculture,
      and their total number of chromosomes was 68 and mostly multiploid. They were
      positive for A2B5 (84.12+/-9.96)%, nestin (73.86+/-5.01)%, and NG2 (73.37+/
      2.09)%. SHG139s cells were induced, and the ratio of positive cells of GFAP, beta
      III tubulin and GalC was (92.89+/-2.24)%, (64.85+/-4.09)% and (33.57+/-4.14)%,
      respectively. CONCLUSIONS: SHG139 is an astroglioma cell line, from which SHG139s
      cells can be successfully obtained by culture with NSCM. SHG139s cells are of
      A2B5(+)/CD133(-) GSCs subgroup cells, with potentials of self-renewal and multi
      directional differentiation. Compared with the intracranial SHG139 xenograft
      tumor, the intracranial SHG139s xenograft tumor is more malignant and aggressive.

PMID- 25975683
TI  - [Preliminary observation on hepatic arterial infusion under temporary hepatic
      circulation occlusion in rabbits].
AB  - OBJECTIVE: To explore the advantages, feasibility and limitations of hepatic
      arterial infusion under temporary hepatic circulation occlusion. METHODS: Twelve
      rabbits were randomly divided into two groups: hepatic artery infusion group (HAI
      group) and hepatic artery infusion under temporary hepatic circulation occlusion
      group (HAI-THCO). Microcatheters were separately inserted into the proper hepatic
      artery and right hepatic vein. For the HAI group, 5-Fu (10 mg/ml and 100 mg/kg)
      was infused into the common hepatic artery with a high pressure injector for 10
      minutes. For the HAI-THCO group, the common hepatic artery and hepatic portal
      vein were temporarily occluded for 15 minutes using artery clamp when 5-Fu was
      being infused. For the two groups, at 2, 5, 10, 15, 20 and 30 min after the start
      of infusion, blood samples of the hepatic flow were collected from the right
      hepatic vein and of the systemic blood flow from the inferior vena cava, 1 ml at
      each time point. The blood drug concentration of these blood samples was
      determined by high performance liquid chromatography (HPLC). RESULTS: Except that
      at 20 and 30 min after infusion, in the HAI group, the blood drug concentration
      of hepatic circulation was significantly higher than that of systemic circulation
      (P < 0.05). But in the HAI-THCO group, the blood drug concentration of hepatic
      circulation was significantly higher than that of systemic circulation at all the
      time points (P < 0.05). The hepatic circulation blood drug level of the HAI-THCO
      group was always significantly higher than that of the HAI group (P < 0.05), but
      the systemic circulation blood drug concentration of the HAI-THCO group was
      always lower (P < 0.05). The hepatic circulation maximum concentration (Cmax) of
      blood drug concentration of the HAI-THCO and HAI groups was (23.057+/-3.270)
      ug/ml and (4.408+/-1.092) ug/ml, respectively, and the Cmax of HAI-THCO group was
      significantly higher (P < 0.001), being 5.23 times of that of HAI group. The
      systemic circulation Cmax of the two groups was (1.456+/-0.217) ug/ml and
      (2.335+/-0.669) ug/ml, respectively, and the Cmax of HAI group was 1.60 times
      higher than that of the HAI-THCO group (P = 0.022). The hepatic circulation AUC
      of HAI-THCO and HAI groups was (368.927+/-52.416) ug.min.ml(-1) and (65.630+/
      14.928) ug.min.ml(-1), respectively. The AUC of HAI-THCO group was 5.62 times
      higher than that of the HAI group (P < 0.001). The systemic circulation AUC of
      the two groups was (27.193+/-3.948) ug.min.ml(-1) and (45.301+/-12.275)
      ug.min.ml(-1), respectively. The AUC of HAI group was 1.67 times higher than that
      of the HAI-THCO group (P = 0.014). CONCLUSIONS: HAI-THCO is a simple and
      effective regional hepatic infusion chemotherapy technique. It can be performed
      through occluding the common hepatic artery and the hepatic portal vein by
      balloon catheter. HAI-THCO can not only increase the blood drug concentration in
      the hepatic circulation, but also decrease the blood drug concentration in the
      systemic circulation, therefore, distinctly lowering the systemic toxicity.

PMID- 25975684
TI  - [Lysophosphatidic acid (LPA) stimulates invasion and metastatic colonization of
      ovarian cancer cells through Rac activation].
AB  - OBJECTIVE: To investigate the mechanisms of lysophosphatidic acid (LPA) in
      stimulating invasion and metastatic colonization of ovarian cancer cells.
      METHODS: The metastatic ability in vivo of ovarian cancer SK-OV3, HEY, OVCAR3,
      and IGROV1 cells was determined in tumor-bearing nude mouse models. Matrigel
      assay was used to detect the changes of response in vitro of ovarian cancer cells
      to LPA after Rac(-) or Rac(+) adenovirus treatment. LPA-induced Rho GTPase
      activation was detected by GST-fusion protein binding assay. RESULTS: The
      peritoneal metastatic colonization assay showed overt metastatic colonization in
      mice receiving SK-OV3 and HEY cell inoculation, indicating that they are invasive
      cells. Metastatic colonization was not detected in animals receiving OVCAR3 and
      IGROV1 cells, indicating that these cells are non-invasive cells. In the matrigel
      invasion assay, exposure to LPA led to a notably greater migratory response in
      metastatic SK-OV3 and HEY cells (Optical density: SK-OV3 cells: 0.594+/-0.023 vs.
      1.697+/-0.049, P<0.01; HEY cells: 0.804+/-0.070 vs. 1.851+/-0.095, P<0.01). But
      LPA did little in the non-metastatic OVCAR3 and IGROV1 cells (Optical density A:
      OVCAR3 cells: 0.336+/-0.017 vs. 0.374+/-0.007, P>0.05; IGROV1 cells: 0.491+/
      0.036 vs. 0.479+/-0.061, P>0.05). LPA migratory responses of ovarian cancer cells
      were closely related to their metastatic colonization capabilities (r = 0.983,
      P<0.05). Rac(-) blocked the LPA response of invasive SK-OV3 and HEY cells (LPA
      induced fold increase of cell migration: SK-OV3 cells: 2.988+/-0.095 vs. 0.997+/
      0.100,P=0.01; HEY cells: 2.404+/-0.059 vs. 0.901+/-0.072, P=0.01). But Rac(+)
      confered the non-invasive cells with LPA response and invasion capability (LPA
      induced fold increase of cell migration: OVCAR3 cells: 1.072+/-0.080 vs. 1.898+/
      0.078, P<0.01; IGROV1 cells: 1.002+/-0.044 vs. 2.141+/-0.057, P<0.05). Among Rho
      GTPases, only Rac activation was different between ovarian cancer cell lines with
      different metastatic capability after LPA stimulation: Cdc42 could not be
      activated in both the invasive and non-invasive cell lines. RhoA could be
      activated in both the invasive and non-invasive cell lines. Rac could be
      activated by LPA in the invasive ovarian cancer cell lines. However, Rac could
      not be activated in the non-invasive cell lines. CONCLUSION: Lysophosphatidic
      acid stimulates invasion and metastasis of ovarian cancer cells through Rac
      activation.

PMID- 25975685
TI  - [Correlation of Rab coupling protein expression with clinicopathological
      characteristics and prognosis in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To explore the RCP protein expression and its clinicopathological
      significance in laryngeal squamous cell carcinoma (LSCC). METHODS: RCP protein
      expression in human head and neck squamous cell carcinoma cell lines (NP-69,
      Tu686, Tu212, M2 and M4) was analyzed by Western blotting. Besides, its
      expression in 87 cases of LSCC, 18 cases of adjacent epithelial mucosa and 16
      cases of vocal cord leukoplakia was detected by immunohistochemistry, and their
      correlation with clinicopathological parameters and patients' outcome was
      analyzed. RESULTS: The NP-69, Tu212 Tu686, M2 and M4 cells showed a gradual
      increase in the expression of RCP protein. The average relative expression levels
      of RCP protein in the NP-69, Tu212, Tu686, M2 and M4 cells were 0.05+/-0.01,
      0.38+/-0.05, 0.63+/-0.02, 0.84+/-0.06 and 0.96+/-0.04, respectively. The same
      situation occurred in the adjacent mucosa, vocal cord leukoplakia and LSCC.
      Specifically, only 3 of 18 adjacent mucosa showed a low RCP expression (scored 0
      2). Although the 16 cases of vocal cord leukoplakia had a low RCP expression, all
      their scores ranged from 0 to 3. While in the LSCC specimens, 59 (67.8%) cases
      demonstrated a high RCP expression (scored 8-15), 18 cases showed a lower RCP
      expression (scored 4-7), and only 10 cases were scored 2-3. Among the 87 LSCC
      cases, there were 28 cases (32.2%) of low RCP expression and 59 cases of high RCP
      expression. All the 18 cases of cancer-adjacent tissues and 16 cases of vocal
      cord leukoplakia were of low RCP expression. RCP overexpression was significantly
      associated with T classification, clinical staging, lymph node metastasis and
      recurrence (P<0.05 for all). Survival analysis revealed that the 5-year survival
      rate was 40.0% in the patients with high RCP expression and 75.0% in the patients
      with low RCP expression, the tumor-free 5-year survival rate was 30.7% and 64.0%,
      respectively, both showing a significant difference between the two subgroups
      (P<0.05). Univariate analysis revealed that alcohol history; smoking, T
      classification, clinical staging, lymph node metastasis and RCP expression were
      significantly associated with a poor prognosis (P<0.05 for all). The multivariate
      analysis showed that only recurrence and RCP expression were independent
      prognostic factors affecting the prognosis for patients with LSCC (P<0.05 for
      both). CONCLUSIONS: Expression of RCP protein may contribute to the malignant
      progression of LSCC, and may become a novel marker predicting tumor recurrence,
      cervical lymph node metastasis and prognosis for patients with laryngeal squamous
      cell carcinoma.

PMID- 25975686
TI  - [Association of polymorphism in the promoter region of PCA3 gene with risk of
      prosate cancer].
AB  - OBJECTIVE: To investigate the polymorphism in the promoter region of PCA3 gene
      and its relationship with risk of prostate cancer (PCa). METHODS: The promoter
      region of PCA3 gene of the DNA of peripheral blood mononuclear cells was detected
      by sequence analysis in the 186 PCa and 141 BPH patients and 135 healthy control
      individuals. If the samples were detected with polymorphism of
      insection/deletion, clone sequence analysis was used with pBS-T carrier to verify
      it. RESULTS: There were 5 polymorphisms. TAAA repeat times: 4, 5, 6, 7, 8, and 8
      genotypes (TAAA 4/5, TAAA 4/6, TAAA 5/5, TAAA 5/6, TAAA 5/7, TAAA 5/8, TAAA 6/6,
      and TAAA 6/7) were detected in the promoter region of PCA3 gene. The eight
      genotypes were divided into three groups: <=10TAAA, 11TAAA, >=12TAAA.
      Unconditional logistic regression analysis models were used to analyze the
      relationship between different genotypes and cancer risks adjusted by sex and
      age. The type 11TAAA and >=12TAAA was associated with higher relative risk for
      prostate cancer than the group <=10TAAA [OR=1.74, 95% CI=1.06-2.87 (for type
      11TAAA); OR=5.63, 95% CI=1.85-17.19 (for type >=12TAAA)]. In the 186 PCa
      patients, there was 62.4% allele of PCA3 gene with AG/CA mutation found in the
      promoter 18-19 bp region of PCA3 gene and it had a close relation with the
      development of prostate cancer. CONCLUSIONS: Short tandem repeats are found in
      the promoter region of the PCA3 gene in PCa patients, and the increase of TAAA
      repeat sequences highly enhance the relative risk of prostate cancer development.
      The occurrence of such STR might be related to the mutations in their upstream
      loci.

PMID- 25975687
TI  - [Expression of colony-stimulating factor 1 in lung adenocarcinoma and its
      prognostic implication].
AB  - OBJECTIVE: This study aimed to explore the expression of tumor-derived colony
      stimulating factor 1 (CSF1), its prognostic significance and underlying related
      mechanisms in resected lung adenocarcinoma (ADC). METHODS: Immunohistochemistry
      and tissue microarray were used to detect the expression of CSF1, epidermal
      growth factor receptor (EGFR), and CD68 in 266 patients with lung adenocarcinoma
      treated in our department between 2004 and 2008. RESULTS: In the 266 ADC cases,
      the positive rates of expression of CSF1, EGFR and CD68 proteins were 56.4%,
      42.1% and 81.2%, respectively. The expression level of CSF1 was positively
      correlated with TNM stage, number of involved nodal stations, tumor recurrence
      and EGFR expression (P<0.05). Univariate analysis indicated that TNM stage,
      number of involved lymph nodes, number of involved nodal stations, CSF1
      expression, the combination of CSF1/EGFR and co-expression of CSF1/CD68/EGFR were
      statistically significant for prognosis (P<0.05). The results of multivariate
      analysis showed that TNM stage, co-expression of CSF1/EGFR and CSF1/CD68/EGFR
      were significant and independent risk factors for survival (P<0.05).
      Correlational analysis showed that expression of CSF1 and EGFR in the tumors was
      positively correlated to the degree of infiltration of interstitial tumor
      associated macrophages (TAMs) (respectively; P<0.05). CONCLUSIONS: The expression
      of CSF1 indicates a poor prognosis in postoperative lung adenocarcinoma. Co
      expression of CSF1 and EGFR may be a valuable independent prognostic predictor,
      and its mechanism is probably involved in the interaction of cancer cells and
      TAMs in the progression of lung adenocarcinoma.

PMID- 25975688
TI  - [Diagnostic value of liver stiffness measurement combined with serum high
      sensitivity C-reactive protein detection in HBV-related cirrhosis patients
      complicated with primary liver cancer].
AB  - OBJECTIVE: The aim of this study was to explore the diagnostic value of liver
      stiffness measurement combined with serum high-sensitivity C-reactive protein
      detection in HBV-related cirrhosis patients complicated with primary liver
      cancer. METHODS: A total of 156 previously untreated chronic hepatitis B-related
      cirrhosis patients and 50 healthy subjects were included in this study. The 156
      patients were divided into two groups: those with primary liver cancer (67 cases)
      and without liver cancer (89 cases). The 50 healthy subjects were considered as
      normal control group. Liver stiffness measurement (LSM) was conducted and serum
      high-sensitivity C-reactive protein (CRP) level was assayed in all the 156
      patients and 50 normal individuals, and their measurement values were
      statistically compared and analyzed. RESULTS: The LSM value was (39.72+/-29.05)
      kPa in the liver cancer patients, significantly higher than the (27.81+/-18.46)
      kPa in the cirrhosis alone patients and (4.25+/-0.74) kPa in the healthy controls
      (P<0.01 for both). Serum hs-CRP levels in the liver cancer patients was 5.81mg/L,
      significantly higher than 1.78 mg/L in the cirrhosis alone patients and 0.38mg/L
      in healthy controls, (P<0.01 for both). The higher the grade of LSM values was,
      the positive rate of CRP was higher in the cirrhosis patients complicated with
      primary liver cancer. In patients with LSM values >=27.6 kPa, the serum CRP
      positive rate was 64.2% in patients with primary liver cancer, significantly
      higher than the 38.0% in patients with cirrhosis alone (P<0.01). In the 67 HBV
      related cirrhosis patients complicated primary liver cancer, the LSM value and
      serum hs-CRP level in AFP-positive patients were (48.95+/-28.59) kPa and 4.91
      mg/L, respectively, higher than those in the AFP-negative patients (28.64+/
      26.83) kPa and 4.16 mg/L, but with a non-significant difference (P>0.05).
      CONCLUSION: Liver stiffness measurement combined with serum high-sensitivity C
      reactive protein detection may have potential diagnostic implications as a marker
      of primary liver cancer occurrence in patients with HBV-related cirrhosis.

PMID- 25975689
TI  - [Association between BRAF V600E mutation and central lymph node metastasis in
      patients with papillary thyroid carcinoma].
AB  - OBJECTIVE: To investigate the association of concomitant BRAFV600E mutation with
      central lymph node metastases in papillary thyroid carcinoma (PTC). METHODS: The
      clinicopathological data of 126 PTC patients who underwent surgical treatment
      within a period of 2 years were retrospectively analyzed. The BRAF V600E gene
      mutation was detected by quantitative fluorescence PCR. RESULTS: The BRAF
      mutation rate was 69.0% (87/126). The univariate analysis showed that BRAF
      mutation status was significantly associated with central lymph node metastasis
      (P<0.05), while the gender, multiple lesions, tumor size, extra-thyroidal
      invasion, Hashimoto's thyroiditis and tumor stage were not significantly
      associated with the BRAF mutation (P>0.05 for all). The multivariate analysis
      showed that only central lymph node metastasis was significantly correlated with
      BRAF mutation (P<0.05). When the diameter of tumor was <=10 mm, BRAF mutation was
      statistically not significantly correlated to central lymph node metastasis
      (P>0.05). When the diameter of tumor was >10 mm, the central lymph node
      metastasis rate was significantly higher in patients with positive BRAF mutation
      than that in patients with a negative BRAF mutation (P<0.05). CONCLUSIONS: The
      presence of BRAF mutation is an independent predictive factor for central lymph
      node metastasis. When PTC is with preoperative positive BRAF mutation, the
      cervical dissection should be routinely performed. The larger the tumor diameter
      is, the more important is the central lymph node dissection. There should be re
      evaluated the necessity of preventative central lymph node dissection when the
      tumor diameter was <=5 mm in patients with negative BRAF mutation.

PMID- 25975690
TI  - [Clinical results of recombinant human endostatin combined with chemoradiotherapy
      for locally advanced nasopharyngeal carcinoma].
AB  - OBJECTIVE: To compare the short-term efficacy and observe the tolerability and
      safety of recombinant human endostatin combined with induction chemotherapy
      followed by chemoradiotherapy for locally advanced nasopharyngeal carcinoma.
      METHODS: Fifty-three patients with locally advanced nasopharyngeal carcinoma, who
      received recombinant human endostatin combined with induction chemotherapy
      followed by chemoradiotherapy, treated in our department from December 2011 to
      March 2013 were included in the study group of this study. Another 48 patients,
      who received induction chemotherapy followed by chemoradiotherapy alone in the
      same period, were chosen as a control group. The short-term outcome, overall
      survival (OS), progression-free survival (PFS), and acute side effects of the two
      groups were compared. RESULTS: The complete remission rates of nasopharyngeal
      tumor in the study and control groups were 77.4% and 72.9%, respectively
      (P=0.154). The complete remission rates of patients with and without cervical
      lymph node metastasis were 75.5% and 62.6%, respectively, showing a significant
      difference (P=0.037). The 2-year OS, PFS, and DMFS rates for the study group were
      82.3%, 77.2%, and 82.2%, respectively, versus 87.2%, 84.3% and 84.2% for the
      control group, showing a non-significant differences between the two groups
      (P=0.938, P=0.551, and P=0.725). CONCLUSIONS: The short-term results of
      recombinant human endostatin (Endostar) combined with induction chemotherapy
      followed by concurrent chemoradiotherapy in the treatment of locally advanced
      nasopharyngeal carcinoma are slightly better than that of induction chemotherapy
      followed by concurrent chemoradiotherapy alone, with tolerable treatment-related
      toxicity and no more side effects.

PMID- 25975691
TI  - [Treatment and prognosis of the carcinoma arising from nasal and sinonasal
      inverted papilloma: report of 62 cases and systematic review].
AB  - OBJECTIVE: To analyze the factors affecting prognosis of the carcinoma arising
      from nasal and sinonasal inverted papilloma. METHODS: The clinicopathological
      data of sixty-two patients treated in our hospital from January 1974 to February
      2012 were retrospectively analyzed. Of the 62 cases, 10 were at stage I or II, 24
      at stage III, and 28 at stage IV. Twenty-six patients were treated with surgery
      alone, and 36 with surgery combined with radiation therapy. Kaplan-Meier method
      and log-rank test were used for the survival analysis. RESULTS: The overall 5
      years survival rate was 39.6%. The 5-years survival rate was 67.5% in the stage I
      or II patients,51.3% in the stage III patients, and 18.3% in the stage IV
      patients (P<0.05). The 5-years survival rate was 65.7% in patients who had no
      surgical history, and 29.9% in patients who had surgery (P<0.05). The 5-year
      survival rate was 17.6% in the group who relapsed after the treatment, and 49.6%
      in the non-relapsed patients (P<0.05). The 5-year survival rate was 23.4% in the
      patients who had involvement of cranial base and (or) orbit, and 47.6% in the
      patients whose cranial base and (or) orbit were clean (P<0.05). Of the patients
      at the same stage (III-IV), the 5-year survival rate of patients treated with
      surgery alone was 32.4%, and those treated with combination therapy was
      36.2%(P=0.89). The univariate analysis showed that clinical stage, surgical
      history before malignization, involvement of the cranial base and (or) orbit
      organs, and post-operative relapse are significantly correlated to prognosis of
      the patients (P<0.05 for all). Multivariate analysis showed that age, clinical
      stage, and previous history of surgery were independent factors affecting the
      prognosis of the patients. Distant metastasis was the major cause of death,
      mostly lung metastases. CONCLUSIONS: Age, clinical stage and surgical history are
      the main factors affecting the prognosis of the patients. The history of
      recurrence and involvement of cranial base or orbit also play an important role
      for the prognosis. Distant metastasis is the main cause of death in the patients
      with carcinoma arising from nasal and sinonasal inverted papilloma.

PMID- 25975692
TI  - [Ultrasonic characteristics of thyroid nodules and diagnostic value of Thyroid
      Imaging Reporting and Data System (TI-RADS) in the ultrosound evaluation of
      thyroid nodules].
AB  - OBJECTIVE: To seek for the ultrasound findings of thyroid nodules related to
      malignancy and benign, and to assess the role of TI-RADS in the ultrosound
      evaluation of thyroid nodules. METHODS: We reviewed and analyzed the ultrasound
      characteristics of 1838 thyroid nodules confirmed by biopsy or surgical
      pathology, classified the thyroid nodules by TI-RADS grading criteria, and
      analyzed the malignancy rate and accuracy rate of different TI-RADS grading.
      RESULTS: Among the 1 838 thyroid nodules, 1 160 cases were carcinomas confirmed
      by surgery, while benign nodules in 212 cases. The sensitivity, specificity, PPV,
      NPV, and accuracy rates were 99.7% (1 156/1 160), 41.0%(278/678), 74.3% (1 156/1
      556), 98.6% (278/282), and 78.2% (1 434/1 838), respectively. There were
      significant differences between the malignant and benign thyroid nodules in echo,
      margin, shape, calcification, and blood flow (P<0.001). Hypoechogenicity, marked
      hypoechogenicity, ill-defined margin, microcalcification, a taller-than-wide
      shape, and nodule internal rich flow (type III) were significantly associated
      with malignancy, while hyper/isoechogenicity, smooth margin, macro/no
      calcifications, a wider-than-tall shape, and nodules internal poor flow (type I
      or type II) were significantly associated with benign nodules. There were
      significant differences between the malignant rates and accuracy rates obtained
      by different TI-RADS classifications (P<0.01). CONCLUSION: Understanding the
      ultrasound characteristics of benign and malignant thyroid nodules and applying
      TI-RADS grading criteria to correctly classify the thyroid nodules are crucial
      for the clinical treatment and prognosis.

PMID- 25975693
TI  - [Analysis of prognostic factors in patients with recurrent and metastatic
      esophageal carcinoma].
AB  - OBJECTIVE: The aim of this study was to explore the influencing factors of
      prognosis for recurrent and metastatic esophageal carcinoma, and to provide
      reference for clinical treatment for these patients. METHODS: The
      clinicopathological and follow-up data of 247 patients with recurrent and
      metastatic esophageal squamous cell carcinoma after radical resection were
      retrospectively reviewed, combined with analysis of prognostic factors in these
      patients. Kaplan-Meier method was used to analyze the survival, difference
      between groups was compared by Log rank test, and Cox model was used for
      multivariate analysis. RESULTS: Among the 247 recurrent and metastatic patients,
      locoregional recurrence was in 139 patients (56.3%), distant metastasis in 60
      patients (24.3%), and combined recurrence in 48 patients (19.4%). The survival
      time was 1 to 42 months in the 247 patients, and the median survival time was 10
      months. The 1-, 3- and 5-year survival rate after recurrence and metastasis was
      26.4%, 6.3% and 2.4%, respectively. Univariate analysis indicated that regional
      lymph node metastasis of the primary tumor, distant lymph node metastasis,
      clinical staging, interval between operation and recurrence, recurrent and
      metastatic patterns, and treatment methods after recurrence and metastasis were
      influencing factors of prognosis (all P<0.05). Cox multivariate analysis
      indicated that clinical staging of the primary tumor, interval between operation
      and recurrence, recurrent and metastatic patterns, and treatment methods after
      recurrence and metastasis were independent factors influencing prognosis (all
      P<0.05). CONCLUSIONS: The prognosis of patients with recurrent and metastatic
      esophageal carcinoma is poor, and it is affected by many factors. Comprehensive
      treatment is effective in prolonging the survival time of the patients.

PMID- 25975694
TI  - [Standards for the diagnosis and treatment of malignant lymphoma (2015 version)
      in China].

PMID- 25975695
TI  - Evidence for cadherin-11 cleavage in the synovium and partial characterization of
      its mechanism.
AB  - INTRODUCTION: Engagement of the homotypic cell-to-cell adhesion molecule cadherin
      11 on rheumatoid arthritis (RA) synovial fibroblasts with a chimeric molecule
      containing the cadherin-11 extracellular binding domain stimulated cytokine,
      chemokine, and matrix metalloproteinases (MMP) release, implicating cadherin-11
      signaling in RA pathogenesis. The objective of this study was to determine if
      cadherin-11 extracellular domain fragments are found inside the joint and if a
      physiologic synovial fibroblast cleavage pathway releases those fragments.
      METHODS: Cadherin-11 cleavage fragments were detected by western blot in cell
      media or lysates. Cleavage was interrupted using chemical inhibitors or short
      interfering RNA (siRNA) gene silencing. The amount of cadherin-11 fragments in
      synovial fluid was measured by western blot and ELISA. RESULTS: Soluble cadherin
      11 extracellular fragments were detected in human synovial fluid at significantly
      higher levels in RA samples compared to osteoarthritis (OA) samples. A cadherin
      11 N-terminal extracellular binding domain fragment was shed from synovial
      fibroblasts after ionomycin stimulation, followed by presenilin 1 (PSN1)
      dependent regulated intramembrane proteolysis of the retained membrane-bound C
      terminal fragments. In addition to ionomycin-induced calcium flux, tumor necrosis
      factor (TNF)-alpha also stimulated cleavage in both two- and three-dimensional
      fibroblast cultures. Although cadherin-11 extracellular domains were shed by a
      disintegrin and metalloproteinase (ADAM) 10 in several cell types, a novel ADAM-
      and metalloproteinase-independent activity mediated shedding in primary human
      fibroblasts. CONCLUSIONS: Cadherin-11 undergoes ectodomain shedding followed by
      regulated intramembrane proteolysis in synovial fibroblasts, triggered by a novel
      sheddase that generates extracelluar cadherin-11 fragments. Cadherin-11 fragments
      were enriched in RA synovial fluid, suggesting they may be a marker of synovial
      burden and may function to modify cadherin-11 interactions between synovial
      fibroblasts.

PMID- 25975697
TI  - Correction.

PMID- 25975696
TI  - A comparison of pathway-independent and pathway-dependent methods in the
      calculation of conformational free enthalpy differences.
AB  - The multistep umbrella sampling method, which belongs to pathway-dependent
      methods to calculate conformational free enthalpy differences, is used to
      calculate the free enthalpy difference between a right-handed 2.710/12 -helix and
      a left-handed 314 -helix of a hexa-beta-peptide in methanol solution. The same
      conformational free enthalpy difference was previously investigated using pathway
      independent methods such as direct counting and enveloping distribution sampling.
      Our results show that the pathway-dependent simulations are sensitive to the
      choice of the pathway and its parameter values. A pathway based on restraining
      distances of hydrogen-bonding atom pairs shows poor sampling for two different
      values of the restraining force constant. Another pathway based on restraining
      backbone dihedral angles did smoothly sample the transition between the two
      helical conformations, but only with a proper choice of the restraining force
      constant. The results illustrate that if, and only if, a proper pathway and
      proper parameters are chosen, the multistep umbrella sampling can be almost 50
      times more efficient than the pathway-independent methods in this case. The
      analysis illustrates the advantages and pitfalls of the much used multistep
      umbrella sampling methodology.

PMID- 25975698
TI  - A DFT study on the insertion of CO2 into styrene oxide catalyzed by 1-butyl-3
      methyl-Imidazolium bromide ionic liquid.
AB  - Green systems able to capture or fix CO(2) are becoming more important specially
      to reduce environmental impacts. In this work, the mechanism of insertion of
      CO(2) into styrene oxide (STYO) both in the absence and presence of the catalyst
      1-butyl-3-methyl-imidazolium bromide (BMIm Br) was investigated through
      calculations based on density functional theory in the omegaB97X-D level. Two
      different routes were considered and it was shown they are energetically
      available and compete against each other. For both routes, the rate-determinant
      step is the ring opening of STYO resulting from the nucleophilic attack of the
      Br(-) on the C atom from STYO and is associated mainly to the participation of
      the cation and the anion from the catalyst in the reaction. Reactive indices and
      noncovalent interaction analysis were used as a tool to investigate this reason.
      This work allowed a better comprehension of the underlying mechanism and the
      supplied data provide valuable support for the design of new more efficient ionic
      liquid catalyst.

PMID- 25975699
TI  - Prefrontal cortex afferents to the anterior temporal lobe in the Macaca
      fascicularis monkey.
AB  - The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to
      the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC
      has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked
      to cognitive processes. The ATL includes several different cortical areas,
      namely, the temporal polar cortex and rostral parts of the perirhinal,
      inferotemporal, and anterior tip of the superior temporal gyrus cortices.
      Multiple sensory modalities converge in the ATL. All of them (except the rostral
      inferotemporal and superior temporal gyrus cortices) are components of the medial
      temporal lobe, which is critical for long-term memory processing. We studied the
      LPFC connections with the ATL by placing retrograde tracer injections into the
      ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and
      inferotemporal cortices (area TE, n = 5), plus one additional deposit in the
      posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits
      into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the
      orbitofrontal cortex (OF; n = 2) were placed for confirmation of those
      projections. The results showed that the vLPFC displays a moderate projection to
      rostral area TE and the dorsomedial portion of the temporal polar cortex; in
      contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC
      and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely,
      A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected
      to the temporopolar cortex, albeit with a lower intensity. The functional
      significance of such paucity of LPFC afferents is unknown.

PMID- 25975700
TI  - Polyacrylic acid polymers hydrogels intended to topical drug delivery:
      preparation and characterization.
AB  - CONTEXT: Bioadhesiviness of polyacrylic acid polymers make them promising
      hydrogels to design topical drug delivery systems, allowing a close contact with
      biological substrate as well as an enhanced local concentration gradient, both
      factors that may improve the biological performance of the drugs. AIM: Texture
      and bioadhesive properties of hydrogels were assessed by using texture analyzer
      and they were correlated with their rheological behavior and performance as drug
      delivery systems. METHODS: Aqueous dispersions of both polymers were prepared at
      0.5%, 1.0% and 1.5% w/v. Hardness, compressibility, adhesiveness, cohesiveness,
      bioadhesion, continuous flow, oscillatory dynamic test and in vitro drug release
      were evaluated. RESULTS: Rheological and texture parameters were dependent on
      polymer concentration and C974P polymer built the strongest structures. Both 1.5%
      hydrogels presented high bioadhesion values. About 50% of the metronidazole (MTZ)
      was sustained released from hydrogels within 2 h with an initial burst release at
      early stage. After, the release rates were decreased and 10% of the MTZ was
      released in the next 10 h. The drug release process was driven by Fickian
      diffusion and complex mechanism for PP and C974P hydrogels, respectively.
      CONCLUSION: The set of results demonstrated that these hydrogels are promising to
      be used as topical controlled drug delivery system.

PMID- 25975701
TI  - Patients' and providers' perceptions of asthma and asthma care: a qualitative
      study.
AB  - BACKGROUND: Differences in patients' and providers' perceptions of asthma and
      asthma care can create barriers to successful treatment. The primary goal of this
      qualitative study was to further explore patient and provider perceptions of
      asthma and asthma care as part of a larger Asthma Comparative Effectiveness
      Study. METHODS: Focus groups held every 6 months for 3 years were designed to
      have a mix of both patients and providers allowing for unique understanding
      around asthma care. RESULTS: The discussion centered on goal setting, asthma
      action plans and prevention strategies for asthma exacerbations. Three
      overarching themes, with a variety of subthemes, emerged as the main findings of
      this study. The three main themes were Cost/Economic Barriers/Process, Self
      Governance/Adherence and Education. CONCLUSIONS: These themes indicated a strong
      need for patient educational interventions around asthma as well as education for
      providers around cost, insurance coverage and patient-centered communication.
      Specifically, education on learning to use inhalers properly, avoiding triggers
      and understanding the importance of a controller medication will benefit patients
      in the long-term management of asthma.

PMID- 25975702
TI  - Impact of symptom management training among asthmatic children and adolescents on
      self-efficacy and disease course.
AB  - PURPOSE: The study was conducted to examine the effect of a training program
      provided to asthmatic children/adolescents on disease course and self-efficacy.
      METHODS: This prospective study consisted of both experimental and control
      subjects. The study population was composed of children/adolescents aged 10-18
      years, who presented at Health Centers within Tokat province with asthma and who
      were currently using inhaler treatments. The study sample included 40 patients
      each in both the control and experimental groups. Asthmatic Child Information
      Form, Disease Evaluation Form, Peak Expiratory Flow Rate Evaluation Form and an
      Asthmatic Child/Adolescent Self-Efficacy Scale were used to collect data on
      research outcomes. Data were statistically analyzed with paired sample t-test,
      McNemar's test, independent samples t-test. RESULTS: A significant increase in
      mean self-efficacy score was observed in the experimental group following
      training sessions. The experimental training was also associated with a reduction
      in asthma symptoms, less limitations to daily function and fewer attacks
      following physical activity relative to the control subjects. The
      children/adolescents in the experimental group were more conscious of the
      symptoms of asthma attacks and used preventive and rescue medications regularly,
      and reported fewer absences from school and fewer emergency room visits (p <
      0.05). The average peak expiratory flow rate was 62.5% in the experimental group.
      After training, there were significant decreases in the number of attacks and the
      need of increasing inhaler doses in the experimental group. CONCLUSIONS: The
      study results show that the training program is effective in increasing self
      efficacy and improving asthma symptoms among children/adolescents. Nurses should
      offer the training program to support children/adolescents during asthma attacks,
      and encourage the development of self-efficacy.

PMID- 25975703
TI  - Applications of emerging imaging techniques for meat quality and safety detection
      and evaluation: A review.
AB  - With improvement in people's living standards, many people nowadays pay more
      attention to quality and safety of meat. However, traditional methods for meat
      quality and safety detection and evaluation, such as manual inspection,
      mechanical methods, and chemical methods, are tedious, time-consuming, and
      destructive, which cannot meet the requirements of modern meat industry.
      Therefore, seeking out rapid, non-destructive, and accurate inspection techniques
      is important for the meat industry. In recent years, a number of novel and
      noninvasive imaging techniques, such as optical imaging, ultrasound imaging,
      tomographic imaging, thermal imaging, and odor imaging, have emerged and shown
      great potential in quality and safety assessment. In this paper, a detailed
      overview of advanced applications of these emerging imaging techniques for
      quality and safety assessment of different types of meat (pork, beef, lamb,
      chicken, and fish) is presented. In addition, advantages and disadvantages of
      each imaging technique are also summarized. Finally, future trends for these
      emerging imaging techniques are discussed, including integration of multiple
      imaging techniques, cost reduction, and developing powerful image-processing
      algorithms.

PMID- 25975704
TI  - Flexible conformable hydrophobized surfaces for turbulent flow drag reduction.
AB  - In recent years extensive work has been focused onto using superhydrophobic
      surfaces for drag reduction applications. Superhydrophobic surfaces retain a gas
      layer, called a plastron, when submerged underwater in the Cassie-Baxter state
      with water in contact with the tops of surface roughness features. In this state
      the plastron allows slip to occur across the surface which results in a drag
      reduction. In this work we report flexible and relatively large area
      superhydrophobic surfaces produced using two different methods: Large roughness
      features were created by electrodeposition on copper meshes; Small roughness
      features were created by embedding carbon nanoparticles (soot) into
      Polydimethylsiloxane (PDMS). Both samples were made into cylinders with a
      diameter under 12 mm. To characterize the samples, scanning electron microscope
      (SEM) images and confocal microscope images were taken. The confocal microscope
      images were taken with each sample submerged in water to show the extent of the
      plastron. The hydrophobized electrodeposited copper mesh cylinders showed drag
      reductions of up to 32% when comparing the superhydrophobic state with a wetted
      out state. The soot covered cylinders achieved a 30% drag reduction when
      comparing the superhydrophobic state to a plain cylinder. These results were
      obtained for turbulent flows with Reynolds numbers 10,000 to 32,500. 

PMID- 25975705
TI  - Simultaneous measurement of cerebral hemoglobin oxygen saturation and blood
      volume in asphyxiated neonates by near-infrared time-resolved spectroscopy.
AB  - BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) usually results in a poor
      clinical outcome even when treated with hypothermic therapy (HT). Early postnatal
      changes in cerebral blood oxygenation and hemodynamics may be critical
      determinants of brain injury and the efficacy of HT. OBJECTIVES: We measured
      cerebral hemoglobin oxygen saturation (ScO2) and cerebral blood volume (CBV) by
      near-infrared time-resolved spectroscopy (TRS) in HT-treated and non-HT-treated
      neonatal HIE patients to assess the influence of these parameters on clinical
      outcome. METHODS: We retrospectively compared ScO2, CBV, and clinical outcomes of
      11 neonates with HIE: 5 were treated by HT (HT-treated; 33.5 degrees C+/-0.5
      degrees C for 72h starting approximately 6h after delivery) and 6 were not (non
      HT-treated). Both CBV and ScO2 were measured by TRS at 6, 24, 48, and 72h after
      birth. Magnetic resonance imaging (MRI) was performed 1-2weeks after birth to
      assess brain injury. RESULTS: Five neonates had adverse outcomes (3 HT-treated, 2
      non-HT-treated). Of these, 1 died within 3days of birth and 4 had abnormal MRI
      findings, including basal ganglia, white matter, and/or thalamic lesions. The
      other 6 neonates had normal MRI findings (favorable outcome). At 6h after birth,
      CBV was significantly higher in neonates with adverse outcomes compared with
      those with a favorable outcome. At 24h after birth, ScO2 was significantly higher
      in neonates with adverse outcomes. Furthermore, we found that combined CBV at 24h
      after birth plus ScO2 had the best predictive ability for neurological outcome:
      sensitivity, specificity, positive predictive value, and negative predictive
      value were all 100%. CONCLUSION: Early postnatal CBV and ScO2 elevations were
      predictive of a poor outcome in HIE. Therefore, measuring combined CBV plus ScO2
      at 24h after birth can allow more precise prediction of neurological outcome.
      Control of postnatal CBV and ScO2 is critical for effective HIE treatment.

PMID- 25975706
TI  - Response: Demography affects spawning location in Northeast Arctic cod, but what
      affects demography?

PMID- 25975707
TI  - Correlation between pH dependence of O2 evolution and sensitivity of Mn cations
      in the oxygen-evolving complex to exogenous reductants.
AB  - Effects of pH, Ca(2+), and Cl(-) ions on the extraction of Mn cations from oxygen
      evolving complex (OEC) in Ca-depleted photosystem II (PSII(-Ca)) by exogenous
      reductants hydroquinone (H2Q) and H2O2 were studied. Two of 4 Mn cations are
      released by H2Q and H2O2 at pHs 5.7, 6.5, and 7.5, and their extraction does not
      depend on the presence of Ca(2+) and Cl(-) ions. One of Mn cations ("resistant"
      Mn cation) cannot be extracted by H2Q and H2O2 at any pH. Extraction of 4th Mn
      ion ("flexible" Mn cation) is sensitive to pH, Ca(2+), and Cl(-). This Mn cation
      is released by reductants at pH 6.5 but not at pHs 5.7 and 7.5. A pH dependence
      curve of the oxygen-evolving activity in PSII(-Ca) membranes (in the presence of
      exogenous Ca(2+)) has a bell-shaped form with the maximum at pH 6.5. Thus, the
      increase in the resistance of flexible Mn cation in OEC to the action of
      reductants at acidic and alkaline pHs coincides with the decrease in oxygen
      evolution activity at these pHs. Exogenous Ca(2+) protects the extraction of
      flexible Mn cation at pH 6.5. High concentration of Cl(-) anions (100 mM) shifts
      the pH optimum of oxygen evolution to alkaline region (around pH 7.5), while the
      pH of flexible Mn extraction is also shifted to alkaline pH. This result suggests
      that flexible Mn cation plays a key role in the water-splitting reaction. The
      obtained results also demonstrate that only one Mn cation in Mn4 cluster is under
      strong control of calcium. The change in the flexible Mn cation resistance to
      exogenous reductants in the presence of Ca(2+) suggests that Ca(2+) can control
      the redox potential of this cation. 

PMID- 25975709
TI  - Experimental determination of the partitioning coefficient of beta-pinene
      oxidation products in SOAs.
AB  - The composition of secondary organic aerosols (SOAs) formed by beta-pinene
      ozonolysis was experimentally investigated in the Juelich aerosol chamber.
      Partitioning of oxidation products between gas and particles was measured through
      concurrent concentration measurements in both phases. Partitioning coefficients
      (Kp) of 2.23 * 10(-5) +/- 3.20 * 10(-6) m(3) MUg(-1) for nopinone, 4.86 * 10(-4)
      +/- 1.80 * 10(-4) m(3) MUg(-1) for apoverbenone, 6.84 * 10(-4) +/- 1.52 * 10(-4)
      m(3) MUg(-1) for oxonopinone and 2.00 * 10(-3) +/- 1.13 * 10(-3) m(3) MUg(-1) for
      hydroxynopinone were derived, showing higher values for more oxygenated species.
      The observed Kp values were compared with values predicted using two different
      semi-empirical approaches. Both methods led to an underestimation of the
      partitioning coefficients with systematic differences between the methods.
      Assuming that the deviation between the experiment and the model is due to non
      ideality of the mixed solution in particles, activity coefficients of 4.82 * 10(
      2) for nopinone, 2.17 * 10(-3) for apoverbenone, 3.09 * 10(-1) for oxonopinone
      and 7.74 * 10(-1) for hydroxynopinone would result using the vapour pressure
      estimation technique that leads to higher Kp. We discuss that such large non
      ideality for nopinone could arise due to particle phase processes lowering the
      effective nopinone vapour pressure such as diol- or dimer formation. The observed
      high partitioning coefficients compared to modelled results imply an
      underestimation of SOA mass by applying equilibrium conditions. 

PMID- 25975708
TI  - Recent breakthroughs in the biology of astaxanthin accumulation by microalgal
      cell.
AB  - Massive accumulation of the secondary ketokarotenoid astaxanthin is a
      characteristic stress response of certain microalgal species with Haematococcus
      pluvialis as an illustrious example. The carotenogenic response confers these
      organisms a remarkable ability to survive in extremely unfavorable environments
      and makes them the richest source of natural astaxanthin. Exerting a plethora of
      beneficial effects on human and animal health, astaxanthin is among the most
      important bioproducts from microalgae. Though our understanding of astaxanthin
      biosynthesis, induction, and regulation is far from complete, this gap is filling
      rapidly with new knowledge generated predominantly by application of advanced
      "omics" approaches. This review focuses on the most recent progress in the
      biology of astaxanthin accumulation in microalgae including the genomic,
      proteomic, and metabolomics insights into the induction and regulation of
      secondary carotenogenesis and its role in stress tolerance of the photosynthetic
      microorganisms. Special attention is paid to the coupling of the carotenoid and
      lipid biosynthesis as well as deposition of astaxanthin in the algal cell. The
      place of the carotenogenic response among the stress tolerance mechanisms is
      revisited, and possible implications of the new findings for biotechnological
      production of astaxanthin from microalgae are considered. The potential use of
      the carotenogenic microalgae as a source not only of value-added carotenoids, but
      also of biofuel precursors is discussed.

PMID- 25975710
TI  - Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and
      ureido-DNJNAc derivatives as new hexosaminidase inhibitors.
AB  - 2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of
      hexosaminidases and therefore show high therapeutic potential for the treatment
      of various diseases, including several lysosomal storage disorders. A
      stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc), the
      iminosugar analog of N-acetylglucosamine, with a high overall yield is here
      described. This novel procedure further allowed accessing ureido-DNJNAc
      conjugates through derivatization of the endocyclic amine on a key pivotal
      intermediate. Remarkably, some of the ureido-DNJNAc representatives behaved as
      potent and selective inhibitors of beta-hexosaminidases, including the human
      enzyme, being the first examples of neutral sp(2)-iminosugar-type inhibitors
      reported for these enzymes. Moreover, the amphiphilic character of the new ureido
      DNJNAc is expected to confer better drug-like properties. 

PMID- 25975715
TI  - Identification and functional characterisation of a novel dopamine beta
      hydroxylase gene variant associated with attention deficit hyperactivity
      disorder.
AB  - OBJECTIVES: Dysregulation in neurotransmitter signalling has been implicated in
      the aetiology of attention deficit hyperactivity disorder (ADHD). Polymorphisms
      of the gene encoding dopamine beta hydroxylase (DBH) have been reported to be
      associated with ADHD; however, small sample sizes have led to inconsistency.
      METHODS: We conducted transmission disequilibrium test analysis in 794 nuclear
      families to examine the relationship between DBH and ADHD. The effects of the
      ADHD-associated polymorphisms on gene expression were assessed by luciferase
      reporter assays in a human neuroblastoma cell line, SH-SY5Y. RESULTS: A SNP
      within the 3' untranslated region of DBH rs129882 showed a significant
      association with ADHD (chi(2) = 9.71, p = 0.0018, OR = 1.37). This association
      remained significant after Bonferroni correction for multiple testing (p = 0.02).
      Further, allelic variation in rs129882 significantly impacted luciferase
      expression. Specifically, the C allele of the ADHD-associated rs129882 SNP
      produced a 2-fold decrease (p < 0.001) in luciferase activity. CONCLUSIONS: These
      data demonstrate for the first time that a DBH gene variant, rs129882, which
      confers risk to ADHD is also associated with reduced in vitro gene expression.
      Reduced DBH expression would be consistent with decreased conversion of dopamine
      to noradrenaline and thus with a relative hypo-noradrenergic state in ADHD.

PMID- 25975714
TI  - Geographic body size variation in the periodical cicadas Magicicada: implications
      for life cycle divergence and local adaptation.
AB  - Seven species in three species groups (Decim, Cassini and Decula) of periodical
      cicadas (Magicicada) occupy a wide latitudinal range in the eastern United
      States. To clarify how adult body size, a key trait affecting fitness, varies
      geographically with climate conditions and life cycle, we analysed the
      relationships of population mean head width to geographic variables (latitude,
      longitude, altitude), habitat annual mean temperature (AMT), life cycle and
      species differences. Within species, body size was larger in females than males
      and decreased with increasing latitude (and decreasing habitat AMT), following
      the converse Bergmann's rule. For the pair of recently diverged 13- and 17-year
      species in each group, 13-year cicadas were equal in size or slightly smaller on
      average than their 17-year counterparts despite their shorter developmental time.
      This fact suggests that, under the same climatic conditions, 17-year cicadas have
      lowered growth rates compared to their 13-years counterparts, allowing 13-year
      cicadas with faster growth rates to achieve body sizes equivalent to those of
      their 17-year counterparts at the same locations. However, in the Decim group,
      which includes two 13-year species, the more southerly, anciently diverged 13
      year species (Magicicada tredecim) was characterized by a larger body size than
      the other, more northerly 13- and 17-year species, suggesting that local
      adaptation in warmer habitats may ultimately lead to evolution of larger body
      sizes. Our results demonstrate how geographic clines in body size may be
      maintained in sister species possessing different life cycles. 

PMID- 25975716
TI  - Non-synonymous mutations mapped to chromosome X associated with andrological and
      growth traits in beef cattle.
AB  - BACKGROUND: Previous genome-wide association analyses identified QTL regions in
      the X chromosome for percentage of normal sperm and scrotal circumference in
      Brahman and Tropical Composite cattle. These traits are important to be studied
      because they are indicators of male fertility and are correlated with female
      sexual precocity and reproductive longevity. The aim was to investigate candidate
      genes in these regions and to identify putative causative mutations that
      influence these traits. In addition, we tested the identified mutations for
      female fertility and growth traits. RESULTS: Using a combination of
      bioinformatics and molecular assay technology, twelve non-synonymous SNPs in
      eleven genes were genotyped in a cattle population. Three and nine SNPs explained
      more than 1% of the additive genetic variance for percentage of normal sperm and
      scrotal circumference, respectively. The SNPs that had a major influence in
      percentage of normal sperm were mapped to LOC100138021 and TAF7L genes; and in
      TEX11 and AR genes for scrotal circumference. One SNP in TEX11 was explained ~13%
      of the additive genetic variance for scrotal circumference at 12 months. The
      tested SNP were also associated with weight measurements, but not with female
      fertility traits. CONCLUSIONS: The strong association of SNPs located in X
      chromosome genes with male fertility traits validates the QTL. The implicated
      genes became good candidates to be used for genetic evaluation, without
      detrimentally influencing female fertility traits.

PMID- 25975717
TI  - Clinical characteristics of narrow-band imaging of oral erythroplakia and its
      correlation with pathology.
AB  - BACKGROUND: To analyze the clinical application of endoscope with narrow-band
      imaging (NBI) system in detecting high-grade dysplasia, carcinoma in situ, and
      carcinoma in oral erythroplakia. METHODS: The demographic, histopathological
      data, and NBI vasculature architectures of patients receiving surgical
      intervention for oral erythroplakia were retrospectively reviewed and analyzed
      statistically. RESULTS: A total of 72 patients, including 66 males and 6 females,
      with mean age of 54.6 +/- 11.2 years, were enrolled. The odds ratio of detecting
      high-grade dysplasia, carcinoma in situ, and carcinoma by twisted elongated
      morphology and destructive pattern of intraepithelial microvasculature was 15.46
      (confidence interval 95%: 3.81-72.84), and the sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy were 80.95%, 78.43%,
      60.71%, 90.91%, and 79.17%, respectively, which were significantly better than
      other two established NBI criteria (p < 0.001). CONCLUSIONS: Twisted, elongated,
      and destructive patterns of intraepithelial papillary capillary loop of NBI
      images are indicators for high-grade dysplasia, carcinoma in situ, and invasive
      carcinoma in oral erythroplakia.

PMID- 25975718
TI  - Quantification of the impact of enzyme-inducing antiepileptic drugs on irinotecan
      pharmacokinetics and SN-38 exposure.
AB  - The population pharmacokinetic model reported here was developed using data from
      2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the
      impact of concomitant therapy with enzyme-inducing antiepileptic drugs (EIAEDs)
      on irinotecan pharmacokinetics. Patients received weekly irinotecan doses of 100
      to 400 mg/m(2) , and plasma samples were collected and analyzed for irinotecan
      and its APC, SN-38, and SN-38G metabolites. Nonlinear mixed-effects modeling was
      employed for population pharmacokinetic analysis. Concomitant therapy with
      phenytoin, phenobarbital, or carbamazepine increased the clearances of
      irinotecan, SN-38, and SN-38G but not APC. SN-38 clearance was 2-fold higher with
      concomitant EIAED use, resulting in 40% lower SN-38 exposure. Evaluation of
      additional covariates revealed no clinically relevant effects of sex or
      concomitant corticosteroid use. The population pharmacokinetic model suggests
      that a 1.7-fold increase in irinotecan dose may compensate for decreases in SN-38
      exposure in the presence of concomitant EIAEDs. Although slightly more
      conservative, this dose adjustment is consistent with those recommended based on
      increases in the maximally tolerated dose for malignant glioma patients receiving
      EIAEDs and may be an appropriate starting point for further investigation when
      extrapolating to other cancer types or alternative regimens. 

PMID- 25975719
TI  - Prevalence and risk factors associated with chronic kidney disease in a Zhuang
      ethnic minority area in China.
AB  - AIM: Numerous studies have examined and reported a high prevalence of chronic
      kidney disease (CKD) in the general population in various countries including
      China. However, the situation may be different in undeveloped rural minority
      regions in China because of China's economic diversity. The aim of the present
      study was to estimate the prevalence of CKD and to analyze its associated factors
      in a Zhuang ethnic minority area in Southwest China. METHODS: A cross-sectional
      survey of a rural minority area populated by people of Zhuang ethnicity in
      Southwest China using multistage, cluster random sampling methods was performed.
      The prevalence of indicators of kidney damage and CKD were calculated and risk
      factors associated with the presence of CKD were analyzed. RESULTS: In total,
      7588 people participated in the study. After adjustment for age and gender, the
      prevalence of albuminuria, haematuria and reduced estimated glomerular filtration
      rate were 2.7%, 3.7%, and 2.2%, respectively. After adjustment for age and
      gender, the prevalence of CKD was 8.3%, while recognition of the disease was
      3.6%. Independent risk factors associated with CKD were age, gender, and
      hypertension. Risk factors independently associated with kidney damage were age,
      gender, hyperuricaemia, and hypertension. CONCLUSION: Our data exhibited a lower
      prevalence and awareness of CKD in undeveloped rural minority regions, especially
      exhibited a low prevalence of albuminuria. This result attributed to the low
      prevalence of metabolic disorders in the local region. Risk factors associated
      with CKD in our study is similar to surveys in other regions of China.

PMID- 25975720
TI  - Applications of DART-MS for food quality and safety assurance in food supply
      chain.
AB  - Direct analysis in real time (DART) represents a new generation of ion source
      which is used for rapid ionization of small molecules under ambient conditions.
      The combination of DART and various mass spectrometers allows analyzing multiple
      food samples with simple or no sample treatment, or in conjunction with
      prevailing protocolized sample preparation methods. Abundant applications by DART
      MS have been reviewed in this paper. The DART-MS strategy applied to food supply
      chain (FSC), including production, processing, and storage and transportation,
      provides a comprehensive solution to various food components, contaminants,
      authenticity, and traceability. Additionally, typical applications available in
      food analysis by other ambient ionization mass spectrometers were summarized, and
      fundamentals mainly including mechanisms, devices, and parameters were discussed
      as well. (c) 2015 Wiley Periodicals, Inc. Mass Spec Rev. 36:161-187, 2017.

PMID- 25975721
TI  - What is the job satisfaction and active participation of medical staff in public
      hospital reform: a study in Hubei province of China.
AB  - BACKGROUND: In China, public hospital reform has been underway for almost 5
      years, and 311 pilot county hospitals are the current focus. This study aimed to
      assess the job satisfaction and active participation of medical staff in the
      reform. A total of 2268 medical staff members in pilot and non-pilot county
      hospitals in Hubei, China, were surveyed. METHODS: Questionnaires were used to
      collect data. The Pearson chi-square statistical method was used to assess the
      differences between pilot and non-pilot county hospitals and identify the factors
      related to job satisfaction as well as the understanding and perception of the
      reform. Binary logistic regression was performed to determine the significant
      factors that influence the job satisfaction of medical staff in pilot county
      hospitals. RESULTS: Medical staff members in pilot county hospitals expressed
      higher satisfaction on current working situation, performance appraisal system,
      concern showed by leaders, hospital management, and compensation packages (P <
      0.05). They were exposed to work-related stress at a higher extent (P < 0.05) and
      half of them worked overtime. Within pilot county hospitals, less than half of
      the medical staff members were satisfied with current job and they have evidently
      less satisfaction on compensation packages and learning and training
      opportunities. The working hours and work stress were negatively related to the
      job satisfaction (P < 0.05). Satisfaction on the performance appraisal system,
      hospital management, compensation packages, and learning and training
      opportunities were positively related to job satisfaction (P < 0.05). Medical
      staff in pilot county hospitals exhibited better understanding of and more
      positive attitude towards the reform (P < 0.05). CONCLUSIONS: Pilot county
      hospitals have implemented some measures through the reform, but there still are
      deficiencies. The government officials and hospital administrators should pay
      attention to influencing factors of job satisfaction and focus on the reasonable
      demands of medical staff. In addition, the medical staff in pilot county
      hospitals exhibited a better understanding of the public hospital reform
      programme and showed more firm confidence, but there still were some medical
      staff members who hold negative attitude. The publicity and education of the
      public hospital reform still need improvement.

PMID- 25975722
TI  - Radial wettable gradient of hot surface to control droplets movement in
      directions.
AB  - A radial wettable gradient was fabricated on the surface of graphite plate by a
      simple one-step anodic oxidation process. It was found that the direction and
      value of the wettable gradient could be easily controlled by adjusting current
      and oxidation time gradient. With the increase of surface temperature, droplets
      on surface not only exhibited the transition of boiling mode, but also showed the
      controlled radial spreading, evaporation and movement behaviors. These phenomena
      could be attributed to the cooperation of wettability force, hysteresis force and
      vapor pressure (Leidenfrost effect). Especially, the controlled radial
      convergence or divergence of droplets with high velocity were realized on the
      surfaces with either inside or outside radial gradient, which would have crucial
      applications in the design of microfluidic devices and the exploration of the
      biotechnology. 

PMID- 25975723
TI  - A Survey of Neonatal Pharmacokinetic and Pharmacodynamic Studies in Pediatric
      Drug Development.
AB  - Conducting clinical trials in neonates is challenging, and knowledge gaps in
      neonatal clinical pharmacology exist. We surveyed the US Food and Drug
      Administration databases and identified 43 drugs studied in neonates or referring
      to neonates between 1998 and 2014. Twenty drugs were approved in neonates. For 10
      drugs, approval was based on efficacy data in neonates, supplemented by
      pharmacokinetic data for four drugs. Approval for neonates was based on full
      extrapolation from older patients for six drugs, and partial extrapolation was
      the basis of approval for four drugs. Dosing recommendations differed from older
      patients for most drugs, and used body-size based adjustment in neonates. Trial
      failures were associated with various factors including inappropriate dose
      selection. Successful drug development in neonates could be facilitated by an
      improved understanding of the natural history and pathophysiology of neonatal
      diseases and identification and validation of clinically relevant biomarkers. 

PMID- 25975724
TI  - Review of eligibility for cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is underused. Recent guidelines have
      expanded indications for CRT to include less severe symptoms but now favor left
      bundle branch block morphology in patients with moderate QRS prolongation. The
      prevalence of CRT eligibility according to historical and current guidelines is
      uncertain. The aim of this review was to identify and synthesize all existing
      published research reporting the prevalence of CRT eligibility. A systematic
      review of electronic databases including MEDLINE, Embase, and the Cochrane
      Library was performed. The primary outcome was the proportion of patients
      eligible for CRT according to historical and current criteria. Secondary outcomes
      included the individual components of eligibility (the ejection fraction,
      symptoms, and QRS duration and morphology). Eligibility estimates were pooled
      using random-effects models because of marked heterogeneity in between-study
      variance. Thirty studies were identified. No study used current guideline
      criteria. On the basis of historical criteria, 11 +/- 3% of ambulatory and 9 +/-
      3% of hospitalized patients are eligible for CRT. However, New York Heart
      Association class II in current guidelines is at least as frequent as New York
      Heart Association III or IV. Approximately 1/3 of patients have QRS prolongation,
      2/3 of whom have left bundle branch block. Only a few patients have non-left
      bundle branch block with QRS duration <150 ms. Medical contraindication or
      ineligibility was rarely assessed. In conclusion, current estimates of need are
      outdated. Inclusion of milder symptoms potentially doubles the eligible
      population. Studies in unselected cohorts are needed to accurately define the
      individual components of eligibility, together with the prevalence and reasons
      for ineligibility.

PMID- 25975725
TI  - Value of neutrophil-lymphocyte ratio in predicting outcomes in Kawasaki disease.
AB  - Total and differential leukocyte counts are useful inflammatory biomarkers. The
      ability of the neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in
      patients with Kawasaki disease (KD) was assessed in this study. All patients with
      KD who underwent consecutive complete blood count analyses during the acute
      febrile phase before intravenous immunoglobulin (IVIG), 2 days after IVIG
      regardless of defervescence, and 3 to 4 weeks after defervescence were enrolled.
      NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR
      values that best predicted IVIG resistance and the development of coronary artery
      abnormalities were determined by receiver-operating characteristic curve and
      multivariate analyses. Of the 587 patients with KD, 222 were IVIG resistant. IVIG
      resistant patients had higher NLRs than IVIG-responsive patients. The best NLR
      cut-off values during the acute febrile phase and 2 days after IVIG for
      predicting IVIG resistance were 5.49 (p <0.001) and 1.26 (p <0.001),
      respectively. Sixty-two patients developed coronary artery abnormalities; 47 had
      coronary dilatation, and 15 had aneurysms. Patients with aneurysms, but not
      patients with dilatation, had higher NLRs than patients without coronary artery
      abnormalities. The best NLR cut-off value 2 days after IVIG for predicting
      aneurysm development was 1.01 (p <0.001). Multivariate analysis revealed that the
      NLR 2 days after IVIG independently predicted coronary aneurysm development (p =
      0.03) and IVIG resistance (p <0.001). In conclusion, the NLR can be used for risk
      stratification in patients with KD. An NLR 2 days after IVIG that exceeded 1 was
      predictive of coronary aneurysm development and IVIG resistance.

PMID- 25975726
TI  - Meta-analysis of the usefulness of Mitraclip in patients with functional mitral
      regurgitation.
AB  - Midterm outcomes for patients presenting with heart failure and functional mitral
      regurgitation (MR) treated with Mitraclip remain unclear. Pubmed, Medline, and
      Google Scholar were systematically searched for studies enrolling patients with
      severe-moderate MR who underwent Mitraclip implantation. All events after at
      least 6 months were the primary safety end point (including death,
      rehospitalization for heart failure, and reinterventions), whereas change in the
      ejection fraction, left ventricular volumes, arterial pulmonary pressure, and
      left atrial diameters were considered as secondary end points. Meta-regression
      analysis was performed to evaluate the effect of baseline clinical and
      echocardiographic parameters on efficacy outcomes: 875 patients were included in
      9 studies; 1.48 clips (1.3 to 1.7) for patients were implanted, and after a
      median follow-up of 9 months (6 to 12), 409 patients (78% [75% to 83%]) were in
      class New York Heart Association I/II and 57 (11% [8% to 14%]) still had moderate
      to-severe MR. Overall adverse events occurred in 137 (26% [20% to 31%]) of the
      patients and 78 (15% [1% to 17%]) of them died; 6-minute walk test improved by
      100 m (83 to 111), whereas a significant reduction in left ventricular volumes
      and systolic pulmonary pressure was reported. At meta-regression analysis, an
      increase in left ventricle systolic volumes positively affected reduction of
      volumes after Mitraclip, whereas atrial fibrillation reduced the positive effect
      of the valve implantation on ejection fraction on end-diastolic and -systolic
      volumes. In conclusion, Mitraclip represents an efficacious strategy for patients
      with heart failure and severe MR. It offers a significant improvement in
      functional class and in cardiac remodeling, in patients with severely dilated
      hearts as well, although its efficacy remains limited in the presence of atrial
      fibrillation.

PMID- 25975727
TI  - Problems in addition to stroke and bleeding after left atrial appendage closure.

PMID- 25975728
TI  - Preoperative factors associated with postoperative requirements of renal
      replacement therapy following cardiac surgery.
AB  - Renal dysfunction is a major adverse event after cardiovascular surgery.
      Therefore, the preoperative prediction of which patients will require renal
      replacement therapy (RRT) after cardiac surgery is an important issue. In the
      present study, 1,822 consecutive patients who underwent cardiovascular surgery
      from 2008 and 2013 at a single institution were reviewed. Patients who were
      already receiving long-term hemodialysis before surgery (n = 134) were excluded.
      The remaining 1,688 patients were separated into 2 groups: those requiring
      postoperative RRT and those without RRT requirement. A total of 128 patients
      (7.6%) required RRT. Patients requiring RRT had greater perioperative blood loss,
      longer intubation time, and longer hospital stays (p <0.0001 for all).
      Multivariate analysis revealed that cardiopulmonary bypass use, preoperative body
      surface area, the left ventricular ejection fraction, serum albumin, and
      creatinine were independent risk factors for postoperative RRT (odds ratios
      2.435, 0.204, 0.976, 0.556, and 5.394, 95% confidence intervals 1.471 to 4.140,
      0.054 to 0.841, 0.962 to 1.025, 0.363 to 0.860, and 3.671 to 8.223, respectively,
      p <0.05 for all). A subgroup of patients with relatively preserved renal function
      before surgery (creatinine <1.12 mg/dl, a cut-off value for RRT requirement
      obtained from receiver-operating characteristic curve analysis [area under the
      curve 0.74748, sensitivity 60.2%, specificity 85.0%]) showed that preoperative
      serum albumin concentration was most significantly associated with postoperative
      RRT requirement (odds ratio 0.048, 95% confidence interval 0.023 to 0.095, p
      <0.0001). In conclusion, cardiopulmonary bypass use, preoperative renal
      impairment as reflected by elevated creatinine level, small body size, a low left
      ventricular ejection fraction, and hypoalbuminemia were associated with a
      requirement for postoperative RRT. In patients with preserved renal function,
      hypoalbuminemia was most significantly related to requirement for RRT. 

PMID- 25975729
TI  - Rethinking clinical response and outcome assessment in a biologic age.
AB  - Standardized response criteria for lymphoma are critical for the evaluation of
      new therapies. Widely adopted recommendations, most recently the Lugano
      classification, have been developed primarily for assessment of conventional
      chemotherapeutic regimens. More recently, several classes of drugs, including
      immunomodulatory agents, B cell receptor pathway targeting kinases, and
      checkpoint (PD-1, PDL-1) inhibitors have demonstrated impressive activity in a
      broad range of histologies. However, they may be associated with features during
      treatment suggestive of progressive disease despite clinical benefit. Immune
      response criteria have been proposed for solid tumors, and a modification is
      needed to be more applicable to lymphomas. Following treatment, conservative use
      of imaging is recommended based on clinical indications. As newer targeted agents
      with unique mechanisms of action are developed, current response and follow-up
      criteria must be made sufficiently flexible for optimal evaluation. 

PMID- 25975730
TI  - Hypoxia-controlled matrix metalloproteinase-9 hyperexpression promotes behavioral
      recovery after ischemia.
AB  - Matrix metalloproteinase-9 (MMP-9) plays a beneficial role in the sub-acute phase
      after ischemic stroke. However, unrestrained MMP-9 may disrupt the blood-brain
      barrier (BBB), which has limited its use for the treatment of brain ischemia. In
      the present study, we constructed lentivirus mediated hypoxia-controlled MMP-9
      expression and explored its role after stroke. Hypoxia response element (HRE) was
      used to confine MMP-9 expression only to the hypoxic region of mouse brain after
      120-min transient middle cerebral artery occlusion. Lentiviruses were injected
      into the peri-infarct area on day 7 after transient ischemia. We found
      hyperexpression of exogenous HRE-MMP-9 under the control of hypoxia, and its
      expression was mainly located in neurons and astrocytes without aggravation of
      BBB damage compared to the CMV group. Furthermore, mice in the HRE-MMP-9 group
      showed the best behavioral recovery compared with the normal saline, GFP, and SB
      3CT groups. Therefore, hypoxia-controlled MMP-9 hyperexpression during the sub
      acute phase of ischemia may provide a novel promising approach of gene therapy
      for stroke. 

PMID- 25975731
TI  - Glycated albumin and the risk of micro- and macrovascular complications in
      subjects with type 1 diabetes.
AB  - BACKGROUND: We investigated the relationship between the glycemic indices
      glycated albumin (GA) and glycated hemoglobin (HbA1c) and the progression of
      diabetic vascular complications [diabetic nephropathy (DN) and carotid artery
      atherosclerosis (CAA)] in subjects with type 1 diabetes (T1D). METHODS: A total
      of 154 participants with a median follow-up of 2.8 years were enrolled in this
      retrospective longitudinal study. We recruited T1D subjects who had regularly
      measured urine albumin-creatinine ratios and estimated glomerular filtration
      rates, as well as tested HbA1c and GA levels consecutively every 3 or 6 months. A
      subgroup of 54 subjects was measured repeated carotid intima-media thickness
      (IMT). RESULTS: We classified subjects into the DN progression (Group I; n = 30)
      with either deteriorated stages of chronic kidney disease (n = 18) or albuminuria
      progression (n = 17), and the non-progression (Group II; n = 124). In multiple
      logistic regression analyses, baseline albuminuria (odds ratio [OR] = 2.64, 95 %
      confidence interval [CI] = 1.03-6.74), mean GA levels (OR = 2.03, 95 % CI = 1.27
      3.26) were significantly associated with progression of DN. However, there was no
      association with mean HbA1c (OR = 0.98, 95 % CI = 0.62-1.54). In a subgroup
      analysis for follow-up measurements of carotid IMT, age was independently
      associated with the presence of plaque and the mean IMT. However glycemic indices
      were not significantly associated with CAA. CONCLUSIONS: Mean GA levels were more
      closely associated with DN progression than mean HbA1c in subjects with T1D.
      However, they were not associated with the CAA.

PMID- 25975732
TI  - Utility scores for vesicoureteral reflux and anti-reflux surgery.
AB  - BACKGROUND: Management of vesicoureteral reflux (VUR) continues to be
      controversial. In conditions of uncertainty, decision analytic techniques such as
      cost-utility analysis (CUA) can help to structure the decision-making process.
      However, CUA analyses require a "utility," a value between 0 (death) and 1
      (perfect health) corresponding to the quality of life associated with a health
      state. Ideally, utility values are elicited directly from representative
      community samples, but utilities have not been rigorously measured for pediatric
      urology conditions. OBJECTIVES: To elicit utility scores for VUR and open anti
      reflux surgery (ARS) from a representative, well-characterized community sample
      of adults who have been parents. METHODS: Cross-sectional survey of nationally
      representative adults who had ever been parents. Each respondent saw one of four
      descriptions of VUR, with or without continuous antibiotic prophylaxis (CAP) and
      occurrence of febrile urinary tract infection (UTI). A 6-week postoperative
      health state following ARS was also assessed. We used the time trade-off (TTO)
      method to elicit utility scores. Factors associated with utility score were
      assessed with a multivariate linear regression model. RESULTS: The survey was
      completed by 1200 individuals. Data were weighted to adjust for demographic
      differences between responders and non-responders. Mean age was 52 +/- 15 years,
      44% were male, and 68% were White. In terms of education, 29% had a college
      degree or higher. The mean utility score for VUR overall was 0.82 +/- 0.28. VUR
      utility scores did not differ significantly based on inclusion of CAP or UTI in
      the health state description (p = 0.21). The 6-week postoperative period garnered
      a utility of 0.71 +/- 0.43. DISCUSSION: Our results showed that VUR has a mean
      utility score of 0.82, which indicates that the community perceives this
      condition to be a substantial burden. For comparison, conditions with similar
      utility scores include compensated hepatitis B-related cirrhosis (0.80) and
      glaucoma (0.82); conditions with higher utilities include neonatal jaundice
      (0.99) and transient neonatal neurological symptoms (0.95); and conditions with
      lower utility scores include severe depression (0.43) and major stroke (0.30).
      Our results suggest that parents consider the burden associated with VUR to be
      significant, and that the impact of the condition on families and children is
      substantial. CONCLUSIONS: VUR is perceived as having a substantial impact on
      health-related quality of life, with a utility value of 0.82. However, use of CAP
      and occurrence of UTI do not seem to affect significantly the community
      perspective on HRQOL associated with living with VUR.

PMID- 25975733
TI  - No effect of basic bladder advice in enuresis: A randomized controlled trial.
AB  - BACKGROUND: There are two firstline, evidence-based treatments available for
      nocturnal enuresis: desmopressin and the enuresis alarm. Prior to use of these
      therapies, international experts usually recommend that the children also be
      given basic bladder training during the daytime. The rationale behind this
      recommendation is that daytime bladder training or urotherapy, is a mainstay in
      the treatment of daytime incontinence caused by detrusor overactivity. Still,
      there is, as yet, no firm evidence that daytime bladder training is useful
      against nocturnal enuresis. AIM: To explore whether basic bladder advice has any
      effect against nocturnal enuresis. STUDY DESIGN: The study was prospective,
      randomized, and controlled. The evaluated intervention was bladder advice, given
      in accordance with ICCS guidelines and focused on regular voiding, sound voiding
      posture, and sufficient fluid intake. Forty children aged 6 years or more with
      previously untreated enuresis, but no daytime incontinence, were randomized (20
      in each group) to receive either first basic bladder advice for 1 month and then
      alarm therapy (group A) or just the alarm therapy (group B). Based on power
      calculations, the minimum number of children required in each treatment arm was
      15. RESULTS: The basic bladder advice did not reduce the enuresis frequency in
      group A (p = 0.089) and the end result after alarm therapy did not differ between
      the two groups (p = 0.74) (see Table). Only four children in group A had a
      partial or full response to bladder training, and two of these children relapsed
      immediately during alarm therapy. DISCUSSION: This was the first study to
      evaluate, in a prospective, randomized manner, the value of daytime basic bladder
      training as a treatment of enuresis. It was found that the treatment neither
      resulted in a significant reduction in the number of wet nights, nor did it
      improve the success of subsequent alarm therapy. CONCLUSIONS: The recommendation
      that all children with enuresis be given bladder training as a firstline therapy
      can no longer be supported. Instead, we recommend that treatment of these
      children start with the enuresis alarm or desmopressin without delay.

PMID- 25975734
TI  - Oxidative stress and epigenetic modifications in the pathogenesis of diabetic
      retinopathy.
AB  - Diabetic retinopathy remains the major cause of blindness among working age
      adults. Although a number of metabolic abnormalities have been associated with
      its development, due to complex nature of this multi-factorial disease, a link
      between any specific abnormality and diabetic retinopathy remains largely
      speculative. Diabetes increases oxidative stress in the retina and its capillary
      cells, and overwhelming evidence suggests a bidirectional relationship between
      oxidative stress and other major metabolic abnormalities implicated in the
      development of diabetic retinopathy. Due to increased production of cytosolic
      reactive oxygen species, mitochondrial membranes are damaged and their membrane
      potentials are impaired, and complex III of the electron transport system is
      compromised. Suboptimal enzymatic and nonenzymatic antioxidant defense system
      further aids in the accumulation of free radicals. As the duration of the disease
      progresses, mitochondrial DNA (mtDNA) is damaged and the DNA repair system is
      compromised, and due to impaired transcription of mtDNA-encoded proteins, the
      integrity of the electron transport system is encumbered. Due to decreased mtDNA
      biogenesis and impaired transcription, superoxide accumulation is further
      increased, and the vicious cycle of free radicals continues to self-propagate.
      Diabetic milieu also alters enzymes responsible for DNA and histone
      modifications, and various genes important for mitochondrial homeostasis,
      including mitochondrial biosynthesis, damage and antioxidant defense, undergo
      epigenetic modifications. Although antioxidant administration in animal models
      has yielded encouraging results in preventing diabetic retinopathy, controlled
      longitudinal human studies remain to be conducted. Furthermore, the role of
      epigenetic in mitochondrial homeostasis suggests that regulation of such
      modifications also has potential to inhibit/retard the development of diabetic
      retinopathy. 

PMID- 25975735
TI  - Conventional aortic valve replacement or transcatheter aortic valve implantation
      in patients with previous cardiac surgery.
AB  - BACKGROUND: Clinical outcomes were compared among patients with previous cardiac
      surgery undergoing transcatheter aortic valve implantation (TAVI) or surgical
      aortic valve replacement (AVR). METHODS: Between 2007 and 2014 a total of 142
      consecutive patients with previous cardiac surgery were treated by TAVI either by
      the transfemoral (n=68) or transapical access (n=74), and 236 patients underwent
      a surgical redo-AVR. Of these patients, propensity analysis (m:n) matched 62
      (group 1, TAVI) and 51 patients (group 2, redo-AVR). A multivariate logistic
      regression model was constructed. Moreover, mortality was compared between both
      groups by Cox regression. RESULTS: Both groups differed significantly (p<0.01) in
      regard to age and preoperative risk scores (EuroSCORE and STS-Score). Thirty-day
      mortality was 14.5% (9/62) in group 1 and 5.8% (3/51) in group 2 (p=0.23). Risk
      adjusted multivariable analysis revealed only the logistic EuroSCORE to be
      strongly correlated with 30-day mortality (p=0.01). Multivariate analysis showed
      no difference in 30-day mortality between both groups (p=0.21). Multivariate Cox
      regression revealed New York Heart Association functional class (p=0.001),
      logistic EuroSCORE (p=0.01), and STS-Score (p=0.03) to be strongly associated
      with overall mortality. Moreover, evaluating overall mortality, Cox regression
      showed no difference between both groups (p=0.36). CONCLUSIONS: The present study
      shows that in patients with cardiac reoperation, TAVI comes with similar outcomes
      when compared to surgical AVR. On the other hand, conventional redo-AVR is still
      a valuable and safe treatment option.

PMID- 25975736
TI  - MicroRNA-141 inhibits migration of gastric cancer by targeting zinc finger E-box
      binding homeobox 2.
AB  - Human microRNA (miR)-141 is a member of the miR-200 family, which has been
      reported to be downregulated in gastric cancer, and involved in the proliferation
      of gastric cancer cells. However, little is currently known regarding its role in
      the migration of gastric cancer. The present study investigated the function of
      miR-141 in gastric cancer cell migration, and evaluated the contribution of zinc
      finger E-box-binding homeobox 1 and 2 (ZEB1/2) in miR-141 mediated migration of
      gastric cancer cells. The expression levels of miR-141 and its potential ZEB1/2
      targets were examined by quantitative polymerase chain reaction (qPCR) and
      western blotting, respectively. The migration of SGC-7901 and HGC-27 gastric
      cancer cells, which had been transfected with an miRNA precursor, was examined by
      cell migration and wound healing assays. A luciferase activity assay was used to
      validate whether ZEB1/2 was a direct target of miR-141. The results demonstrated
      that overexpression of miR-141 markedly inhibited the migration of gastric cancer
      cells in vitro. Forced overexpression of miR-141 significantly reduced the
      luciferase activity of the 3'-untranslated region of ZEB2 in gastric cancer
      cells. Furthermore, the mRNA and protein expression levels of ZEB2 were reduced
      in cells overexpressing miR-141, whereas the protein expression levels of E
      cadherin were increased. In gastric tumor samples the expression levels of ZEB2
      were inversely correlated with the expression of miR-141. These results suggest
      that miR-141 may be involved in the inhibition of gastric cancer cell migration,
      and that ZEB2 is a target gene of miR-141. 

PMID- 25975737
TI  - Coherent control of plasma dynamics.
AB  - Coherent control of a system involves steering an interaction to a final coherent
      state by controlling the phase of an applied field. Plasmas support coherent wave
      structures that can be generated by intense laser fields. Here, we demonstrate
      the coherent control of plasma dynamics in a laser wakefield electron
      acceleration experiment. A genetic algorithm is implemented using a deformable
      mirror with the electron beam signal as feedback, which allows a heuristic search
      for the optimal wavefront under laser-plasma conditions that is not known a
      priori. We are able to improve both the electron beam charge and angular
      distribution by an order of magnitude. These improvements do not simply correlate
      with having the 'best' focal spot, as the highest quality vacuum focal spot
      produces a greatly inferior electron beam, but instead correspond to the
      particular laser phase front that steers the plasma wave to a final state with
      optimal accelerating fields. 

PMID- 25975738
TI  - Temporal changes in dissolved 137Cs concentrations in groundwater and stream
      water in Fukushima after the Fukushima Dai-ichi Nuclear Power Plant accident.
AB  - The concentration of dissolved 137Cs in groundwater and stream water in the
      headwater catchments in Yamakiya district, located ~35 km north west of Fukushima
      Dai-ichi Nuclear Power Plant (FDNPP), was monitored from June 2011 to July 2013,
      after the earthquake and tsunami disaster. Groundwater and stream water were
      sampled at intervals of approximately 2 months at each site. Intensive sampling
      was also conducted during rainstorm events. Compared with previous data from the
      Chernobyl NPP accident, the concentration of dissolved 137Cs in stream water was
      low. In the Iboishi-yama catchment, a trend was observed for the concentration of
      dissolved 137Cs in stream water to decline, which could be divided into two
      phases by October 2011 (a fast flush of activity as a result of rapid washoff and
      a slow decline as a result of soil fixation and redistribution processes). The
      highest 137Cs concentration recorded at Iboishi-yama was 1.2 Bq/L on August 6,
      2011, which then declined to 0.021-0.049 Bq/L during 2013 (in stream water under
      normal water-flow conditions). During the rainfall events, the concentration of
      dissolved 137Cs in stream water increased temporarily. The concentration of
      dissolved 137Cs in groundwater at a depth of 30 m at Iboishi-yama displayed a
      decreasing trend from 2011 to 2013, with a range from 0.039 Bq/L to 0.0025 Bq/L.
      The effective half-lives of stream water in the initial fast flush and secondary
      phases were 0.10-0.21 and 0.69-1.5 y, respectively in the three catchments. The
      effective half-life of groundwater was 0.46-0.58 y at Koutaishi-yama and 0.50-3.3
      y at Iboishi-yama. The trend for the concentration of dissolved 137Cs to decline
      in groundwater and stream water was similar throughout 2012-2013, and the
      concentrations recorded in deeper groundwater were closer to those in stream
      water. The declining trend of dissolved 137Cs concentrations in stream water was
      similar to that of the loss of canopy 137Cs by throughfall, as shown in other
      reports of forest sites in the Yamakiya district.

PMID- 25975739
TI  - Complete genome sequence and intracellular protein localization of Datura yellow
      vein nucleorhabdovirus.
AB  - A limited number of plant rhabdovirus genomes have been fully sequenced, making
      taxonomic classification, evolutionary analysis and molecular characterization of
      this virus group difficult. We have for the first time determined the complete
      genome sequence of 13,188 nucleotides of Datura yellow vein nucleorhabdovirus
      (DYVV). DYVV genome organization resembles that of its closest relative, Sonchus
      yellow net virus (SYNV), with six ORFs in antigenomic orientation, separated by
      highly conserved intergenic regions and flanked by complementary 3' leader and 5'
      trailer sequences. As is typical for nucleorhabdoviruses, all viral proteins,
      except the glycoprotein, which is targeted to the endoplasmic reticulum, are
      localized to the nucleus. Nucleocapsid (N) protein, matrix (M) protein and
      polymerase, as components of nuclear viroplasms during replication, have
      predicted strong canonical nuclear localization signals, and N and M proteins
      exclusively localize to the nucleus when transiently expressed as GFP fusions. As
      in all nucleorhabdoviruses studied so far, N and phosphoprotein P interact when
      co-expressed, significantly increasing P nuclear localization in the presence of
      N protein. This research adds to the list of complete genomes of plant-infecting
      rhabdoviruses, provides molecular tools for further characterization and supports
      classification of DYVV as a nucleorhabdovirus closely related to but with some
      distinct differences from SYNV. 

PMID- 25975740
TI  - Efficacy and safety of low accelerating dose regimen of interferon/ribavirin
      antiviral therapy in patients with hepatitis C virus recurrence after liver
      transplantation.
AB  - BACKGROUND: Achievement of sustained virological response (SVR) is the main goal
      of interferon/ribavirin (IFN/RBV) antiviral therapy in patients with hepatitis C
      virus (HCV) recurrence after orthotopic liver transplantation (OLT). In this
      study, we have retrospectively evaluated the efficacy and safety of low
      accelerating dose regimen (LADR) of IFN/RBV in patients with HCV recurrence after
      OLT. MATERIAL AND METHODS: Thirty-one patients with HCV recurrent after OLT who
      were treated with LADR of antiviral therapy were analyzed in our study. Data of
      virological response (including rapid, early, end of treatment and sustained
      virological responses, designated as RVR, EVR, ETVR, and SVR, respectively) and
      liver histological change were collected. RESULTS: All patients received
      tacrolimus (TAC) and/or mycophenolate mofetil (MMF) for immunosuppression. Seven
      patients (23%), 6 patients (19%), and 18 patients (58%) finished complete
      treatment (CT), complete duration (CD), and incomplete treatment (IT),
      respectively. Twenty-four patients (77%) achieved ETVR. Among them, 8 patients
      (33%) achieved SVR, while 16 (67%) patients relapsed within 24 weeks after the
      end of the treatment. Univariate analysis showed that pretreatment viral load
      (p=0.002) as well as treatment dose and duration (p<0.001) were positively
      associated with SVR. Flu-like side effects were observed in all patients and 17
      (54.8%) discontinued treatment due to adverse events. CONCLUSIONS: SVR
      achievement and tolerability to LADR of IFN/RBV therapy in our study are moderate
      in patients with HCV recurrence after liver transplantation. Pretreatment viral
      load and treatment dose and duration are positively related to SVR.

PMID- 25975741
TI  - Superior Hypogastric Nerve Block to Reduce Pain After Uterine Artery
      Embolization: Advanced Technique and Comparison to Epidural Anesthesia.
AB  - PURPOSE: To evaluate a modified superior hypogastric nerve block (SHNB) to reduce
      pain after uterine artery embolization (UAE) compared to epidural anesthesia.
      MATERIALS AND METHODS: In this retrospective study, the amount of opiate drugs
      needed after UAE was compared between SHNB and epidural anesthesia. Eighty one
      consecutive women (mean age: 43.67 years) were in the SHNB group and 27
      consecutive women (mean age: 43.48 years) treated earlier at the same institution
      in the epidural anesthesia group. UAE was performed from a unilateral femoral
      artery approach using a 4F catheter. 500-700 or 700-900 MUm trisacryl gelatine
      microspheres were used as embolic agents. The SHNB was performed by advancing a
      21G from the abdominal wall below the umbilicus to the anterior portion of the
      5th vertebral body. For optimal guidance a cranio-caudal tilt of 5 degrees -15
      degrees  was used. On a lateral view the correct contrast distribution in front
      of the vertebral body is confirmed. Then 20 ml local anesthesia (ropivacain 0.75
      %) is injected. In case of an asymmetric right-left distribution the needle was
      repositioned. RESULTS: All SHNB were successful without severe complications. The
      mean time for the SHNB was 4 min 38 s (2 min 38 s-9 min 27 s). The needle was
      repositioned in average 0.87 times. The opiate dose for the SHNB group was 19.33
      +/- 22.17 mg which was significantly lower. The average time to receive an opiate
      drug after SHNB was 4 h 41 min. CONCLUSION: The SHNB is a safe and minimally time
      consuming way to reduce pain after UAE especially within the first 4 h.

PMID- 25975742
TI  - Endovascular Recanalization of Chronically Occluded Native Arteries After Failed
      Bypass Surgery in Patients with Critical Ischemia.
AB  - OBJECTIVE: The study aimed to evaluate the feasibility, safety, and outcome of
      endovascular recanalization of native chronic total occlusions (CTO) in patients
      with critical limb ischemia (CLI) and lower extremities bypass graft failure.
      METHODS: A retrospective review of CLI patients with failed lower limb grafts
      (>30 days after surgery) that underwent recanalization of native CTO was
      conducted in two institutions from January 2010 to June 2014. Twenty-eight
      patients (28 limbs) were included in the study, and all had limited surgical
      revascularization options. Demographics, procedural data, technical success,
      complications, vessel patency, limb salvage rates, and survival rates were
      analyzed. RESULTS: The mean follow-up period was 12.8 months. The technical
      success rate was 92.9% (26/28 limbs). The combined ipsilateral antegrade
      retrograde approach was performed in nine limbs (32.1%). Major periprocedural
      (<30 days) complications included two myocardial infarctions (7.1%) and two stent
      thromboses (7.1%), resulting in one amputation. The ankle brachial index before
      discharge was significantly improved after recanalization (0.78 +/- 0.08 vs. 0.31
      +/- 0.10, p < 0.01). The primary, assisted primary, and secondary patency rates
      at 12 months were 52.2, 65.8, and 82.2%, respectively. The limb salvage rate and
      amputation-free survival rate at 12 months were 91.6 and 87.0%, respectively.
      CONCLUSIONS: Endovascular recanalization of native CTO in patients with graft
      failure-related CLI is a feasible, safe, and effective procedure, with reasonable
      technical success, vessel patency, and limb salvage rates. The technique should
      be attempted before amputation in patients with limited surgical
      revascularization options.

PMID- 25975743
TI  - Renal Function Recovery After Revascularization with Percutaneous Angioplasty of
      a Patient on Chronic Hemodialysis.

PMID- 25975744
TI  - Tension Pneumopericardium as a Complication of Preoperative Localization of a
      Small Pulmonary Metastasis Using a Short Hook Wire and Suture System.

PMID- 25975745
TI  - Sequential backbone assignment based on dipolar amide-to-amide correlation
      experiments.
AB  - Proton detection in solid-state NMR has seen a tremendous increase in popularity
      in the last years. New experimental techniques allow to exploit protons as an
      additional source of information on structure, dynamics, and protein interactions
      with their surroundings. In addition, sensitivity is mostly improved and
      ambiguity in assignment experiments reduced. We show here that, in the solid
      state, sequential amide-to-amide correlations turn out to be an excellent,
      complementary way to exploit amide shifts for unambiguous backbone assignment.
      For a general assessment, we compare amide-to-amide experiments with the more
      common (13)C-shift-based methods. Exploiting efficient CP magnetization transfers
      rather than less efficient INEPT periods, our results suggest that the approach
      is very feasible for solid-state NMR. 

PMID- 25975746
TI  - Low-level laser therapy on bone repair: is there any effect outside the
      irradiated field?
AB  - The biological effects of local therapy with laser on bone repair have been well
      demonstrated; however, this possible effect on bone repair outside the irradiated
      field has not been evaluated. The aim of this study was to investigate the effect
      of low-level laser therapy (LLLT) (lambda = 830 nm) on repair of surgical bone
      defects outside the irradiated field, in rats. Sixty Wistar rats were submitted
      to osteotomy on the left femur and randomly separated into four groups (n = 15):
      group I, control, bone defect only; group II, laser applied on the right femur
      (distant dose); group III, laser applied locally on the bone defect and also on
      the right femur (local and distant doses); and group IV, laser applied locally on
      the left femur (local dose). Laser groups received applications within a 48-h
      interval in one point per session of density energy (DE) = 210 J/cm(2), P = 50
      mW, t = 120 s, and beam diameter of 0.028 cm. Five animals of each group were
      euthanized 7, 15, and 21 days after surgery. Histologic analysis in all groups
      showed new bone formation in the region of interest (ROI) at 7 days. After 15
      days, bone remodeling with a decrease of bone neoformation in the marrow area was
      observed in all groups. After 21 days, advanced bone remodeling with new bone
      mostly located in the cortical area was observed. The histomorphometric analysis
      showed at 7 days a significant increase of bone formation in groups III and IV
      compared to groups I and II. At days 15 and 21, histomorphometric analysis showed
      no significant differences between them. Laser therapy presented a positive local
      biostimulative effect in the early stage of bone healing, but the LLLT effect was
      not observed a long distance from the evaluated area. 

PMID- 25975747
TI  - Identification of key transcription factors in caerulein-induced pancreatitis
      through expression profiling data.
AB  - The current study aimed to isolate key transcription factors (TFs) in caerulein
      induced pancreatitis, and to identify the difference between wild type and Mist1
      knockout (KO) mice, in order to elucidate the contribution of Mist1 to
      pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression
      Omnibus database then analyzed using the t-test. The isolated differentially
      expressed genes (DEGs) were mapped into a transcriptional regulatory network
      derived from the Integrated Transcription Factor Platform database and in the
      network, the interaction pairs involving at least one DEG were screened. Fisher's
      exact test was used to analyze the functional enrichment of the target genes. A
      total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice
      treated with caerulein, respectively. DEGs screened in Mist1KO mice were
      predominantly enriched in apoptosis, mitogen-activated protein kinase signaling
      and other cancer-associated pathways. A total of 188 and 51 TFs associated with
      pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of
      the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated
      protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell
      division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2
      (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These
      TFs were predominantly involved in phosphorylation, DNA replication, cell
      division and DNA mismatch repair. In addition, specific TFs, including
      minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase
      (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function
      in the unwinding of DNA were identified to participate in Mist1KO pancreatitis.
      The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the
      regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs
      were also involved in this type of regulation.

PMID- 25975748
TI  - Reduced vitreal concentration of periostin after vitrectomy in patients with
      proliferative diabetic retinopathy.

PMID- 25975749
TI  - Methodologies for producing amylose: A review.
AB  - Three main in vitro approaches can be distinguished for obtaining amylose (AM):
      enzymatic synthesis, AM leaching, and AM complexation following starch
      dispersion. The first uses alpha-d-glucose-1-phosphate (G1P), a glucosyl primer
      with a degree of polymerization (DP) of at least 4 and phosphorylase (EC
      2.4.1.1), commonly from potatoes. Such approach provides AM chains with low
      polydispersity, the average DP of which can be manipulated by varying the
      reaction time and the ratio between G1P, primer, and enzyme dose. AM leaching is
      the result of heating a starch suspension above the gelatinization temperature.
      This approach allows isolating AM on large scale. The AM DP, yield, and purity
      depend on the heating rate, leaching temperature, shear forces and botanical
      origin. High leaching temperatures (80-85 degrees C) result in mostly pure AM of
      DP >1000. At higher temperatures, lower purity AM is obtained due to amylopectin
      leaching. Annealing as pretreatment and ultracentrifugation or repetitive organic
      solvent-based precipitations after leaching are strategies, which improve the
      purity of AM extracts. When AM is separated by complex formation, complete
      dispersion of starch is followed by bringing AM into contact with, e.g., n
      butanol or thymol. The resultant complex is separated from amylopectin as a
      precipitate. Complete starch dispersion without degradation is critical for
      obtaining AM of high purity. Finally, higher DP AM can be converted enzymatically
      into AM fractions of lower DP.

PMID- 25975750
TI  - Mir-203-mediated tricellulin mediates lead-induced in vitro loss of blood
      cerebrospinal fluid barrier (BCB) function.
AB  - The blood-cerebrospinal fluid barrier (BCB) plays a critical role in the
      maintenance of optimal brain function. Tricellulin (TRIC), a protein localized at
      the tricellular contact sites of epithelial cells is involved in the formation of
      tight junctions in various epithelial barriers. However, little is known about
      its expression in the choroidal epithelial cells. It is well established that
      lead (Pb) exposure increases the leakage of the BCB. The purpose of this study is
      to investigate the expression and localization of TRIC in choroidal epithelial
      cells in vitro and whether altered TRIC expression mediates Pb-induced loss of
      barrier function. We found that TRIC protein and mRNA were expressed in choroidal
      epithelial cells in vitro and TRIC was localized at the tricellular contacts,
      colocalizing with occludin. Downregulation of TRIC by siRNA increased the BCB
      permeability corroborated by altered transendothelial electrical resistance
      (TEER) and FITC-dextran flux. Treatment with 10MUM Pb reduced TRIC protein
      expression, but overexpression of TRIC alleviated the Pb-induced increase in BCB
      permeability. Bioinformatics analysis showed that mir-203 was a potential
      microRNA (miRNA) binding motif on TRIC 3'UTR, and that Pb exposure increased the
      expression of mir-203. Treatment with a mir-203 inhibitor increased TRIC protein
      expression and attenuated the Pb-induced BCB leakage. Our results establish that
      TRIC plays an important role in regulating BCB function. 

PMID- 25975751
TI  - MicroRNA-194-5p could serve as a diagnostic and prognostic biomarker in
      myelodysplastic syndromes.
AB  - Trisomy 8 and trisomy 1q are the most frequent chromosomal abnormalities in
      Korean patients with myelodysplastic syndrome (MDS). MicroRNA (miRNA)
      deregulation is involved in the development of hematological malignancies,
      including MDS, and cancer-associated genomic regions are known to encode miRNAs.
      The aim of the present study was to investigate the involvement of miRNAs encoded
      by chromosomes 8 and 1q in MDS. For this, the expression of nine miRNAs encoded
      by chromosome 8 (miR-30b-5p, miR-30d-5p, miR-101-3p, miR-124-3p, miR-151a-5p, miR
      320a, miR-486-5p, miR-596, and miR-875-5p) and three miRNAs encoded by chromosome
      1q (miR-29c-3p, miR-194-5p, and miR-214-3p) was compared between 65 MDS patients
      and 11 controls. We found a significant upregulation of miR-194-5p (5.1-fold,
      P=0.002) and miR-320a (2.94-fold, P=0.016) in MDS patients compared with
      controls. The patients with low miR-194-5p expression showed a significantly
      decreased overall survival (P=0.049). The areas under the miR-194-5p and miR-320a
      ROC curves were 0.797 (P=0.002) and 0.729 (P=0.016), respectively. Although these
      findings need to be validated in a larger patient population, our results
      indicate that miR-194-5p is a candidate diagnostic biomarker for MDS and that low
      miR-194-5p expression could be associated with poor overall survival for MDS
      patients. 

PMID- 25975752
TI  - Downregulated miR-33b is a novel predictor associated with disease progression
      and poor prognosis in multiple myeloma.
AB  - MiRNAs located at chromosome fragile sites play important roles in regulating
      critical genes associated with myeloma pathogenesis, disease progression and drug
      resistance. Our previous results have identified miR-33b (located in chromosome
      17p) was one of the dysregulated miRNAs in the sera of newly diagnosed MM
      patients. However, little is known about its expression pattern in myeloma tumor
      cells and its prognostic value in MM patients. In the present study, we
      investigated the expression pattern of miR-33b in 58 newly diagnosed, 11
      relapsed, 12 remission MM patients and 18 health donors by quantitative real-time
      PCR. Our results showed the expression of miR-33b was obviously down-regulated in
      newly diagnosed and relapsed MM patients compared to remission patients and
      health donors (p<0.001). Moreover, patients with del(13q), del(17p), t(4;14) and
      high-risk genetic abnormalities have lower expression levels of miR-33b compared
      to patients without those of abnormalities (p=0.032, 0.018, 0.034, 0.005).
      Survival analysis showed patients with miR-33b low expression had significantly
      shortened PFS (p=0.016) and OS (p=0.033) and might be associated with drug
      resistance to bortezomib-based treatment. Our data suggest that down-regulated
      miR-33b might be a novel predictor associated with disease progression and poor
      prognosis in MM. 

PMID- 25975753
TI  - Tenotomy or tenodesis for pathology of the long head of the biceps brachii: a
      systematic review and meta-analysis.
AB  - PURPOSE: The objective of this meta-analysis is to compare clinical outcomes of
      tenotomy and tenodesis in the surgical treatment of long head of the biceps
      brachii (LHB). METHODS: A literature search was conducted in Embase and PubMed
      from 2000 to April 2014. All studies comparing the clinical outcomes between LHB
      tenotomy and tenodesis were included. The quality assessment was done by
      utilizing the Coleman score. We included nine studies comprising 650 patients
      undergoing LHB tenotomy or tenodesis, mostly with concomitant shoulder pathology.
      RESULTS: No significant difference in post-operative Constant score (mean
      difference 1.77), elbow flexion strength (mean difference 0), and forearm
      supination strength (mean difference 0.01) in favour of tenodesis was observed. A
      Popeye deformity (odds ratio 0.17) and cramping pain (odds ratio 0.38) in the
      bicipital groove muscle were less frequently seen in patients treated with
      tenodesis. The Coleman score ranged between 45 and 100 in the included studies.
      CONCLUSION: Based on this meta-analysis, no differences in post-operative
      functional outcome between tenotomy and tenodesis for the treatment of LHB
      lesions were observed. A Popeye deformity and cramping pain in the bicipital
      groove are more frequently observed in patients treated with tenotomy. LEVEL OF
      EVIDENCE: IV.

PMID- 25975754
TI  - Complications associated with 133 static, antibiotic-laden spacers after TKA.
AB  - PURPOSE: Periprosthetic infection after total knee arthroplasty (TKA) is a
      devastating complication, with a two-stage revision currently the 'gold standard'
      treatment for chronic infections. There is, however, a lack of information about
      mechanical complications during this treatment. The purpose of this study was to
      determine: (1) the rate and type of mechanical complications encountered during a
      two-stage exchange revision for periprosthetic infection of the knee and (2)
      possible factors of influence. METHODS: Between 2000 and 2011, 133 patients
      received an antibiotic-laden cement spacer as part of a two-stage protocol. The
      overall frequency and types of complication were recorded (fissure/fracture of
      the tibia or femur, spacer fracture, subluxation of the patella, peroneus
      affection, wound healing disorder and mobilization under anaesthesia based on a
      constricted ROM). Also analysed were potential influencing factors (BMI, ASA
      classification, length of the interval with the enclosed spacer, revision needed
      after explantation, revision needed after reimplantation, complications after
      primary TKA, service life of the primary prosthesis) in terms of the overall
      outcome (possibility of reimplantation, complications during the two-stage
      protocol). RESULTS: The mean age at the time of the first stage operation was
      70.1 +/- 9.9 years. Overall, 20 of 133 patients suffered one of the complications
      mentioned above (15 %). Fracture/fissure of the tibia occurred in nine cases (6.8
      %) and fracture/fissure of the femur in three (2.3 %). There were also three
      mobilizations under anaesthesia after TKA reimplantation, two affections of the
      peroneus nerve, one spacer fracture, one subluxation of the patella and one wound
      healing disorder. The influencing factors on the overall outcome were revision
      after reimplantation (reinfection, p = 0.002), revision after explantation
      (reinfection, p = 0.044), prior aseptic revision after primary TKA
      (reimplantation, p = 0.019), and prior two-stage revision (reimplantation, p =
      0.002). CONCLUSION: A two-stage revision arthroplasty using a static cement
      spacer is an effective therapy for infected TKAs. The complication rate of 15 %
      (including restricted ROM after reimplantation) is acceptable. Influencing
      factors (revision needed after reimplantation, revision needed after
      explantation) can be demonstrated and should be avoided during the two-stage
      protocol.

PMID- 25975755
TI  - An expression system for Gustatory receptors - and why it failed.
AB  - A recent paper by the Dahankuar laboratory suggested that single Drosophila sugar
      receptors proteins accurately mediate sugar detection when ectopically expressed
      in olfactory neurons of the antenna. These findings contra-dict numerous
      previously published electrophysiological and behavioral investigations, which
      all point towards heteromultimeric sugar taste receptors. Here, I provide some
      explanation why this "pseudo-heterologous" expression system may have led to this
      misleading conclusion. 

PMID- 25975758
TI  - Increased mortality for pregnancy-associated melanoma: different outcomes pooled
      together, selection and publication biases.

PMID- 25975756
TI  - Kinesin, 30 years later: Recent insights from structural studies.
AB  - Motile kinesins are motor proteins that move unidirectionally along microtubules
      as they hydrolyze ATP. They share a conserved motor domain (head) which harbors
      both the ATP- and microtubule-binding activities. The kinesin that has been
      studied most moves toward the microtubule (+)-end by alternately advancing its
      two heads along a single protofilament. This kinesin is the subject of this
      review. Its movement is associated to alternate conformations of a peptide, the
      neck linker, at the C-terminal end of the motor domain. Recent progress in the
      understanding of its structural mechanism has been made possible by high
      resolution studies, by cryo electron microscopy and X-ray crystallography, of
      complexes of the motor domain with its track protein, tubulin. These studies
      clarified the structural changes that occur as ATP binds to a nucleotide-free
      microtubule-bound kinesin, initiating each mechanical step. As ATP binds to a
      head, it triggers orientation changes in three rigid motor subdomains, leading
      the neck linker to dock onto the motor core, which directs the other head toward
      the microtubule (+)-end. The relationship between neck linker docking and the
      orientations of the motor subdomains also accounts for kinesin's processivity,
      which is remarkable as this motor protein only falls off from a microtubule after
      taking about a hundred steps. As tools are now available to determine high
      resolution structures of motor domains complexed to their track protein, it
      should become possible to extend these studies to other kinesins and relate their
      sequence variations to their diverse properties. 

PMID- 25975757
TI  - The implications on clinical diagnostics of using microRNA-based biomarkers in
      exercise.
AB  - Regular exercise is one of the best ways to maintain health and to prevent and
      control several chronic diseases. Identifying the molecular mechanisms associated
      with benefits of exercise is crucial and miRNAs have been suggested to be key
      players. Understanding the roles of miRNAs in these processes provides an
      opportunity to improve the clinical application of using exercise as a
      therapeutic intervention. Circulating miRNAs particularly are promising
      candidates for non-invasive biomarkers, which would enable oriented
      interventions. Furthermore, better and easier ways to assess exercise capacity
      can impact exercise evaluations and prescriptions, minimizing risks and
      monitoring the exercise response better. This review summarizes the current
      knowledge of miRNAs, recent advancements in miRNAs associated with exercise and
      addresses their role as biomarkers for exercise-related biological responses. 

PMID- 25975759
TI  - Quantification of apoptosis and necroptosis at the single cell level by a
      combination of Imaging Flow Cytometry with classical Annexin V/propidium iodide
      staining.
AB  - Precisely identifying the type of programmed cell death is one of the key
      questions in contemporary biomedical research. We developed a straightforward
      approach allowing quantitative discrimination between two types of cell death on
      the single cell level: apoptosis and necroptosis. This method uses the
      combination of imaging flow cytometry with classical Annexin V/propidium iodide
      staining, which allows for the ascertainment of typical features of dying cells:
      exposure of the phospholipid phosphatidylserine and the loss of membrane
      integrity. Image-based analysis of nuclear morphology enables us to distinguish
      between secondary necrotic/late apoptotic and necroptotic cells directly in one
      assay. This is a major advantage compared to other contemporary approaches of
      necroptosis detection, which require a parallel application of several methods.
      This approach can be used for the quantitative assessment of cell death in cell
      and systems biology studies of signal transduction networks. 

PMID- 25975760
TI  - Application and applicability of non-invasive risk models for predicting
      undiagnosed prevalent diabetes in Africa: A systematic literature search.
AB  - BACKGROUND AND PURPOSE: Prediction algorithms are increasingly advocated in
      diabetes screening strategies, particularly in developing countries. We conducted
      a systematic review to assess the application and applicability of existing non
      invasive prevalent diabetes risk models to populations within Africa. DESIGN:
      systematic review data sources A systematic search of English literatures in
      Medline via PubMed from 1999 until June, 2014. Study selection Included studies
      had to report on the development, validation or implementation of a model that
      was primarily constructed to predict prevalent undiagnosed diabetes using non
      laboratory based predictors. DATA EXTRACTION: Data were extracted on the type of
      statistical model, type and range of predictors in the model, performance
      measures in both internal and external validation, and whether the model was
      developed from, validated or implemented in an African population. RESULTS:
      Twenty-three studies reporting on non-invasive prevalent diabetes models were
      identified. Ten from Europe (some with multiethnic populations), nine models were
      developed among Asian population, two from the USA and two from the Middle-East.
      The c-statistics for these models ranged from 0.65 to 0.88 in the development
      studies, and from 0.63 to 0.80 in the validation studies. Twenty models were
      validated, and none in Africa. Among predictors commonly included in models,
      parental/family history of diabetes and personal history of hypertension appear
      to be more prone to measurement errors in the African context. CONCLUSION:
      Existing prevalent diabetes prediction models have not been applied to African
      populations, and issues with the measurement of key predictors make their
      applicability likely inaccurate.

PMID- 25975761
TI  - CT staging and monitoring of fibrotic interstitial lung diseases in clinical
      practice and treatment trials: a position paper from the Fleischner Society.
AB  - CT is increasingly being used to stage and quantify the extent of diffuse lung
      diseases both in clinical practice and in treatment trials. The role of CT in the
      assessment of patients entering treatment trials has greatly expanded as clinical
      researchers and pharmaceutical companies have focused their efforts on developing
      safe and effective drugs for interstitial lung diseases, particularly for
      idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous
      approval by the US Food and Drug Administration of two new drugs for the
      treatment of idiopathic pulmonary fibrosis. CT features are a key part of the
      inclusion criteria in many drug trials and CT is now being used to refine the
      type of patients enrolled. Interest in the potential use of serial CT as an
      effectiveness endpoint is increasing. For chronic progressive diseases, mortality
      may not be a feasible endpoint and many surrogate markers have been explored,
      ranging from pulmonary function decline to biomarkers. However, these surrogate
      markers are not entirely reliable and combinations of endpoints, including change
      in disease extent on CT, are being investigated. Methods to assess disease
      severity with CT range from simple visual estimates to sophisticated
      quantification by use of software. In this Position Paper, which cannot be
      regarded as a comprehensive set of guidelines in view of present knowledge, we
      examine the uses of serial CT in clinical practice and in drug trials and draw
      attention to uncertainties and challenges for future research. 

PMID- 25975762
TI  - Clinical effect of four different ointment bases on healthy cat eyes.
AB  - OBJECTIVE: To describe the effects of long-term treatment with four different eye
      ointment bases (OBs) in cats. ANIMALS STUDIED: Ten healthy cats. PROCEDURES: The
      study was performed in two periods. Four different OBs were tested. Hundred grams
      of OB contained the following: OB-A: 35.17 g liquid paraffin (lp), 64.83 g white
      petrolatum (wp); OB-B: 10.03 g lp, 84.95 g wp 5.02 g lanolin; OB-C: 18.34 g lp,
      51.40 g wp, 25.00 mg KH2 PO4 , 57.00 mg K2 HPO4 , 18.90 g eucerinum anhydricum,
      11.28 g water for injections; and OB-D: 70 g unguentum lanalcoli, 20 g lp, 10 g
      aqua conservans. One eye was treated, and the other served as a negative control.
      Cats received the OBs TID for 28 days. The two study periods were separated by a
      4-month washout phase. Samples for conjunctival impression cytology, swabs for
      bacteriologic and mycologic examination, and cytobrush samples for FHV-1 and
      Chlamydophila felis PCR detection were obtained. Both eyes were examined daily.
      Severity of ocular symptoms was scored using a modified Draize eye irritation
      test. A total of five eyes were treated with OB-A, five with OB-B, four with OB
      C, and five with OB-D. RESULTS: Treated eyes had significantly higher clinical
      scores. Eyes receiving OB-A had the highest overall clinical score. The results
      of bacteriologic and mycologic examination concur with the previously published
      data. All samples tested were negative for FHV-1 and Chlamydophila felis. There
      was no significant difference between treated and control eyes upon cytological
      examination. CONCLUSION: The application of OBs resulted in clinical symptoms in
      treated eyes. The long-term use of ointments is not well tolerated in cats and
      may lead to ocular irritation.

PMID- 25975763
TI  - Quantum supercharger library: hyper-parallelism of the Hartree-Fock method.
AB  - We present here a set of algorithms that completely rewrites the Hartree-Fock
      (HF) computations common to many legacy electronic structure packages (such as
      GAMESS-US, GAMESS-UK, and NWChem) into a massively parallel compute scheme that
      takes advantage of hardware accelerators such as Graphical Processing Units
      (GPUs). The HF compute algorithm is core to a library of routines that we name
      the Quantum Supercharger Library (QSL). We briefly evaluate the QSL's performance
      and report that it accelerates a HF 6-31G Self-Consistent Field (SCF) computation
      by up to 20 times for medium sized molecules (such as a buckyball) when compared
      with mature Central Processing Unit algorithms available in the legacy codes in
      regular use by researchers. It achieves this acceleration by massive
      parallelization of the one- and two-electron integrals and optimization of the
      SCF and Direct Inversion in the Iterative Subspace routines through the use of
      GPU linear algebra libraries. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25975766
TI  - List predatory journal publications separately from genuine scholarly
      publications as standard for CVs.

PMID- 25975765
TI  - Acute medical impairment among elderly patients involved in motor vehicle
      collisions.
AB  - BACKGROUND: The association between acute medical illness and motor vehicle
      collisions (MVCs) among elderly emergency department patients is unclear. We
      sought to determine the prevalence of acute medical conditions that might impair
      driving ability among the elderly involved in MVCs and determine if there was an
      increased risk of the driver having an acute medical condition compared to
      similarly aged passengers. METHODS: We reviewed charts of patients aged 65 years
      or older whose emergency department visit was prompted by a motor vehicle
      collision between 1 July 2000 and 30 June 2010 at two Level 1 trauma centres. The
      exposure of interest was occupancy status (driver vs. passenger), and the outcome
      measure was the presence of any predefined acute medical illness that might
      impair driving ability. RESULTS: Final analysis included 871 drivers (cases) and
      307 passengers (controls). An acute medical illness was recorded in 107 patients
      (9%): 97 drivers (11%) and 10 passengers (3%). Compared to passengers, drivers
      had significantly higher odds of presenting with acute medical illness (OR 3.7,
      95% CI 1.9-7.2). After controlling for potential confounders, the adjusted odds
      ratio was 5.5 (95% CI 2.3-13.0). CONCLUSION: Acute medical conditions are a
      moderately common diagnosis among elderly drivers, presenting in about one in ten
      patients. A difference in the risk of finding an acute medical illness when
      comparing elderly drivers and passengers evaluated in the emergency department
      after a collision suggests the need for considering additional diagnostic
      investigation and post-discharge surveillance in this population.

PMID- 25975767
TI  - Control of cutaneous leishmaniasis caused by Leishmania major in south-eastern
      Morocco.
AB  - OBJECTIVE: The incidence of cutaneous leishmaniasis (CL) caused by Leishmania
      major has increased in Morocco over the last decade, prompting the Ministry of
      Health to take intersectoral response measures including vector and reservoir
      control. The aim of this article was to describe the CL outbreak response
      measures taken in the province of Errachidia, where the reservoir of L. major, a
      sand rat (Meriones shawi), was targeted using strychnine-poisoned wheat baits
      from 2010 to 2012. METHOD: We analysed routine surveillance data and other
      information using the data of the CL control programme. RESULTS: We present data
      on the evolution and the extension of CL in this province as well as the
      epidemiological profile of the disease. Between 2004 and 2013, 7099 cases of CL
      were recorded in Errachidia Province, gradually affecting all districts. Our
      results demonstrate that more women were affected than men and that all age
      groups were represented. CONCLUSION: Errachidia Province was the epicentre of the
      recent CL outbreak in Morocco. A notable decline in incidence rates was observed
      after 2011. The outbreak control measures may have contributed to this decline,
      as well as climatic trends or progressing herd immunity.

PMID- 25975768
TI  - Factors that influence the way local communities respond to consultation
      processes about major service change: A qualitative study.
AB  - OBJECTIVES: In England, proposed service changes such as Emergency Department
      closures typically face local opposition. Consequently, public consultation
      exercises often involve protracted, hostile debates. This study examined a
      process aimed at engaging a community in decision-making about service
      reconfiguration, and the public response to this process. METHODS: A documentary
      analysis was conducted to map consultation methods used in an urban area of
      England where plans to consolidate hospital services on fewer sites were under
      discussion. In-depth interviews (n=20) were conducted with parents, older people,
      and patient representatives. The analysis combined inductive and deductive
      approaches, informed by risk communication theories. RESULTS: The commissioners
      provided a large volume of information about the changes, alongside a programme
      of public events. However, the complexity of the process, together with what
      members of the public perceived to be the commissioners' dismissal of their
      concerns, led the community to question their motivation. This was compounded by
      a widespread perception that the proposals were financially driven. DISCUSSION:
      Government policy emphasises the importance of clinical leadership and 'evidence'
      in public consultation. However, an engagement process based on this approach
      fuelled hostility to the proposals. Policymakers should not assume communities
      can be persuaded to accommodate service change which may result in reduced access
      to care.

PMID- 25975769
TI  - Evaluation of a policy to strengthen case management and quality of diabetes care
      in general practice in Denmark.
AB  - OBJECTIVES: To evaluate the utilization of a policy for strengthening general
      practitioner's case management and quality of care of diabetes patients in
      Denmark incentivized by a novel payment mode. We also want to elucidate any
      geographical variation or variation on the basis of practice features such as
      solo- or group practice, size of practice and age of the GP. METHODS: On the
      basis registers encompassing reimbursement data from GPs and practice specific
      information about geographical location (region), type of practice (solo- or
      group-practice), size of practice (number of patients listed) and age of the GP
      were are able to determine differences in use of the policy in relation to the
      practice-specific information. RESULTS: At the end of the study period (2007
      2012) approximately 30% of practices have enrolled extending services to
      approximately 10% of the diabetes population. There is regional--as well as
      organizational differences between GPs who have enrolled and the national
      averages with enrolees being younger, from larger practices and with more
      patients listed. CONCLUSIONS: Our study documents an organizationally and
      regionally varied and limited utilization with the overall incentive structure
      defined in the policy not strong enough to move the majority of GPs to change
      their way of delivering and financing care for patients with diabetes within a
      period of more than 5 years.

PMID- 25975770
TI  - Erratum to: NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal
      cancer: screening in 1969 patients with various cancers.

PMID- 25975771
TI  - Treatment of platelets with riboflavin and ultraviolet light mediates complement
      activation and suppresses monocyte interleukin-12 production in whole blood.
AB  - BACKGROUND AND OBJECTIVES: Pathogen inactivation (PI) and storage may alter the
      immunomodulatory capacity of platelets (PLTs). The aim of this study was to
      examine the effect of PI (Riboflavin and ultraviolet light treatment) and storage
      on the capacity of PLTs to induce cytokine responses in recipient inflammatory
      cells. MATERIALS AND METHODS: A pool and split design was used to prepare
      untreated and PI-treated buffy coat-derived platelet concentrates (PCs). Samples
      were taken on days 2 and 7 postcollection and incubated with ABO/RhD-matched
      fresh whole blood for 6 h with or without lipopolysaccharide (LPS). The
      intracellular production of IP-10, MCP-1, MIP-1alpha, IL-8, IL-6, IL-10, IL-12,
      TNF-alpha and MIP-1beta in monocytes and neutrophils was assessed using flow
      cytometry. Complement proteins in PLT supernatants were measured using a
      cytometric bead array. RESULTS: PLTs and PLT supernatant (both untreated and PI
      treated) resulted in modulation of intracellular MIP-1beta and IL-12 production
      in monocytes. Compared to untreated PLTs, PI-treated PLTs resulted in
      significantly lower LPS-induced monocyte IL-12 production (day 7). The
      concentration of C3a and C5a (and their desArg forms) was significantly increased
      in PLT supernatants following PI. CONCLUSION: PI results in decreased LPS-induced
      monocyte IL-12 production and increased complement activation. The association
      between platelet-induced complement activation and IL-12 production warrants
      further investigation.

PMID- 25975773
TI  - Megastudies, crowdsourcing, and large datasets in psycholinguistics: An overview
      of recent developments.
AB  - This paper introduces and summarizes the special issue on megastudies,
      crowdsourcing, and large datasets in psycholinguistics. We provide a brief
      historical overview and show how the papers in this issue have extended the field
      by compiling new databases and making important theoretical contributions. In
      addition, we discuss several studies that use text corpora to build
      distributional semantic models to tackle various interesting problems in
      psycholinguistics. Finally, as is the case across the papers, we highlight some
      methodological issues that are brought forth via the analyses of such datasets. 

PMID- 25975772
TI  - A biochemical network can control formation of a synthetic material by sensing
      numerous specific stimuli.
AB  - Developing bio-compatible smart materials that assemble in response to
      environmental cues requires strategies that can discriminate multiple specific
      stimuli in a complex milieu. Synthetic materials have yet to achieve this level
      of sensitivity, which would emulate the highly evolved and tailored reaction
      networks of complex biological systems. Here we show that the output of a
      naturally occurring network can be replaced with a synthetic material. Exploiting
      the blood coagulation system as an exquisite biological sensor, the fibrin clot
      end-product was replaced with a synthetic material under the biological control
      of a precisely regulated cross-linking enzyme. The functions of the coagulation
      network remained intact when the material was incorporated. Clot-like
      polymerization was induced in indirect response to distinct small molecules,
      phospholipids, enzymes, cells, viruses, an inorganic solid, a polyphenol, a
      polysaccharide, and a membrane protein. This strategy demonstrates for the first
      time that an existing stimulus-responsive biological network can be used to
      control the formation of a synthetic material by diverse classes of physiological
      triggers. 

PMID- 25975774
TI  - Influence of surgical orthodontic treatment on masticatory function in skeletal
      Class III patients.
AB  - Skeletal Class III patients exhibit malocclusion characterised by Angle Class III
      and anterior crossbite, and their occlusion shows total or partially lateral
      crossbite of the posterior teeth. Most patients exhibit lower bite force and
      muscle activity than non-affected subjects. While orthognathic surgery may help
      improve masticatory function in these patients, its effects have not been fully
      elucidated. The aims of the study were to evaluate jaw movement and the
      electromyographic (EMG) activity of masticatory muscles before and after
      orthognathic treatment in skeletal Class III patients in comparison with control
      subjects with normal occlusion. Jaw movement variables and EMG data were recorded
      in 14 female patients with skeletal Class III malocclusion and 15 female controls
      with good occlusion. Significant changes in jaw movement, from a chopping to a
      grinding pattern, were observed after orthognathic treatment (closing angle P <
      0.01; cycle width P < 0.01), rendering jaw movement in the patient group similar
      to that of the control group. However, the grinding pattern in the patient group
      was not as broad as that of controls. The activity indexes, indicating the
      relative contributions of the masseter and temporalis muscles (where a negative
      value corresponds to relatively more temporalis activity and vice versa) changed
      from negative to positive after treatment (P < 0.05), becoming similar to those
      of control subjects. Our findings suggest that orthognathic treatment in skeletal
      Class III patients improves the masticatory chewing pattern and muscle activity.
      However, the chewing pattern remains incomplete compared with controls.

PMID- 25975776
TI  - [Mapping of risks related to medication care in nursing homes: An overview in
      Alsace - France].
AB  - BACKGROUND: Medication care of patients in nursing homes involves a complex
      circuit whose related risks need to be identified. The aim of this study was
      first to map risks related to medication care in a representative panel of
      nursing homes under contract with community pharmacies in Alsace, then to propose
      improvement action plans to remedy the weaknesses identified. METHODS: This study
      was conducted on a representative sample of 23 nursing homes in Alsace in 2014. A
      self-assessment questionnaire (Interdiag EHPAD), divided into 7 fields and made
      up of 198 questions, was completed by each of the 23 nursing homes during
      multidisciplinary meetings that were organized by the OMEDIT (observatoire du
      medicament, des dispositifs medicaux et de l'innovation therapeutique of Alsace).
      The percentages of controlled risks were calculated for each of the 7 fields of
      the medication circuit, both at nursing home and regional levels. Similarly, the
      percentages of non-controlled risks were calculated for each of the 198 items.
      RESULTS: Considering the 7 fields, regional percentages of controlled risks
      varied from 63% to 85%. The field relative to drug supply was the best
      controlled, while that relative to prevention was the least controlled.
      Considering the 198 items, 30 important vulnerability points were identified,
      among which stand out: failure to report and to analyze adverse drug events, lack
      of involvement of general practitioner in nursing homes through collaborative
      approaches and transcription by nurse staff of oral or handwritten prescriptions
      in medical software. The analysis of those items led to the proposal of 13
      improvement actions. CONCLUSION: The study pointed out mainly difficulties linked
      to the absence of suitable risk management policies and the lack of adjustment
      between nursing home staffs and general practitioners. In contrast, it revealed
      that the collaboration between nursing homes and community pharmacies was
      successful overall. Finally, we hope that this multi-center study, that led to
      identify concrete proposals, will help nursing homes to improve the quality of
      medication care for their residents.

PMID- 25975777
TI  - [Determinants of patient and health system delays for women with breast cancer in
      Morocco, 2013].
AB  - BACKGROUND: In Morocco, breast cancer is the first most common cancer in women.
      It is diagnosed in most cases at an advanced stage. Delay in diagnosis and access
      to treatment for breast cancer increases morbidity and mortality. The objective
      of this study was to determine the consultation delay (patient delay), diagnosis
      delay and access to treatment delay (health system delays) of women with breast
      cancer admitted at the National Institute of Oncology in Rabat. Factors
      associated with these delays were analyzed. METHODS: We conducted a cross
      sectional study from December 2012 to May 2013 at the National Institute of
      Oncology in Rabat. Two hundred eligible and consenting women were interviewed
      using a structured and pre-tested questionnaire. Stages I and II were identified
      as "early stages" and III and IV as "advanced stages". RESULTS: In our
      population, 54% were diagnosed at an early stage of breast cancer and 46% at an
      advanced stage. The median total delay was 120 days (interquartile interval
      [IIQ]=81-202 days). The patient delay (median=65 days, IIQ=31-121) was longer
      than the health system delay (median=50 days, IIQ=29-77). High risk for a long
      total delay (more than 4 months) was observed for women who were aged over 65
      years (OR=1.30, 95% CI 1.10-4.20), illiterate (OR=4.50, 95% CI 2.10-6.20), rural
      residents (OR=3.40, 95% CI 1.23-8.13), in a lower socioeconomic category
      (OR=4.75, 95% CI 1.45-15.60), without knowledge about breast self-examination
      (OR=5.67, 95% CI 2.65-12.15) and seen more than 2 times before diagnosis
      (OR=7.70, 95% CI 2.88-20.50). A long total delay increased the risk of being
      diagnosed at an advanced stage (OR=5.62, 95% CI 3.03-10.45). CONCLUSION: Efforts
      should be directed to providing good information to the population at risk,
      better access to screening and continuing medical training to enable diagnosis
      and early treatment.

PMID- 25975775
TI  - Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice.
AB  - Cortical interneurons are generated predominantly in the medial ganglionic
      eminence (MGE) and migrate through the ventral and dorsal telencephalon before
      taking their final positions within the developing cortical plate. Previously we
      demonstrated that interneurons from Robo1 knockout (Robo1(-/-)) mice contain
      reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less
      responsive to the chemorepulsive actions of semaphorin ligands expressed in the
      striatum and affecting their course of migration (Hernandez-Miranda et al. [2011]
      J. Neurosci. 31:6174-6187). Earlier studies have highlighted the importance of
      Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1
      in this process. We observed significantly fewer cells expressing the interneuron
      markers Gad67 and Lhx6 in the cortex of PlexinA1(-/-) mice compared with wild
      type littermates at E14.5 and E18.5. Although the level of apoptosis was similar
      in the mutant and control forebrain, proliferation was significantly reduced in
      the former. Furthermore, progenitor cells in the MGE of PlexinA1(-/-) mice
      appeared to be poorly anchored to the ventricular surface and showed reduced
      adhesive properties, which may account for the observed reduction in
      proliferation. Together our data uncover a novel role for PlexinA1 in forebrain
      development.

PMID- 25975778
TI  - [Relevance of the health insurance databases to study spatial disparities in
      asthma prevalence: A study in southeastern France].
AB  - BACKGROUND: Data on asthma prevalence at a small-area level would be useful to
      set up and monitor French local public health policies. This study, based on drug
      reimbursement databases in southeastern France, aimed to (1) compare asthma-like
      disorders prevalence estimated by using three different indicators; (2) study
      sociodemographic characteristics associated with these indicators; (3) verify
      whether these indicators are equivalent to study geographical disparities of the
      asthma-like disorders prevalence at a small-area level. METHODS: The study was
      conducted among the beneficiaries of the National Health Insurance Fund aged 18
      44 years residing in southeastern France in 2010 (n=1,371,816). Using data on
      asthma drugs reimbursements (therapeutic class R03), we built three indicators to
      assess asthma-like disorders prevalence: at least 1, 2 or 3 purchase(s) in 2010.
      We analyzed sociodemographic characteristics associated with these indicators,
      and their geographical disparities at a small-area level using multilevel
      logistic regression models. RESULTS: The crude asthma-like disorders prevalence
      varied between 2.6 % and 8.4 % depending on the indicator. It increased with age,
      was higher for women than for men, and among low-income people for all three
      indicators. We measured significant geographical disparities. Areas with high
      prevalence rates were the same regardless of the indicator. CONCLUSION: The
      indicators built in this study can be useful to identify high prevalence areas.
      They could contribute to launch discussion on environmental health issues at the
      local level.

PMID- 25975779
TI  - Excited state interactions between the chiral Au38L24 cluster and covalently
      attached porphyrin.
AB  - A protected S-acetylthio porphyrin was synthesized and attached to the Au38(2
      phenylethanethiolate)24 cluster in a ligand exchange reaction. Chiral high
      performance liquid chromatography of the functionalized cluster yielded
      enantiomeric pairs of clusters probably differing in the binding site of the
      porphyrin. As proven by circular dichroism, the chirality was maintained. Exciton
      coupling between the cluster and the chromophore is observed. Zinc can be
      incorporated into the porphyrin attached to the cluster, as evidenced by
      absorption and fluorescence spectroscopy, however, the reaction is slow.
      Quenching of the chromophore fluorescence is observed, which can be explained by
      energy transfer from the porphyrin to the cluster. Transient absorption spectra
      of Au38(2-phenylethanethiolate)24 and the functionalized cluster probe the bleach
      of the gold cluster due to ground state absorption and the characteristic excited
      state absorption signals. Zinc incorporation does not have a pronounced effect on
      the photophysical behaviour. Decay times are typical for the molecular behaviour
      of small monolayer protected gold clusters. 

PMID- 25975780
TI  - Laparoscopic Hernia Repair With 3-Millimeter Instruments: A Point of Technique
      and Illustrative Case Video.
AB  - The repair of inguinal hernia has been a controversial issue in surgical practice
      since its conception. The article demonstrates that use of 3 mm instruments can
      be incorporated in Laparoscopic hernia repair. The second aim of this article is
      that use of TAP block (Transverse abdominal plane block) without curare is
      efficient, safe and reproducible. 

PMID- 25975781
TI  - [An overview of the treatment of lymphoma by regulating the intra-tumoral and
      extra-tumoral environment].

PMID- 25975782
TI  - [Screening of citrullinated proteins in ten tumor cell lines].
AB  - OBJECTIVE: The conversion of arginine into citrulline, termed citrullination, has
      important consequences for the structure and function of proteins. The present
      study aimed to identify novel citrullinated proteins in 10 tumor cell lines by 2
      D Western blotting (2-D WB). METHODS: Two identical two-dimensional
      electrophoresis (2-DE) gels were prepared using extracts from ten cultured human
      tumor cell lines: ECA(esophageal cancer cells), HEPG2 (hepatocellular carcinoma
      cells), SKOV3 (ovarian cancer cells), MCF-7 (breast cancer cells), H292 (lung
      mucoepidermoid carcinoma cells), HeLa (cervical cancer cells), Lovo (colon cancer
      cells), OS-RC (renal cell carcinoma cells), PANC-1 (pancreatic cancer cells), and
      SGC (gastric cancer cells). The expression profiles on one 2-DE gels were trans
      blotted to PVDF membranes, and the blots were then probed with an anti-citrulline
      antibody. By comparing the 2-DE profile with the parallel 2-D WB profile at a
      global level, protein spots with immuno-signals were collected from the second 2
      DE gel and identified using mass spectrometry. Immunoprecipitation was used to
      verify the expression and citrullination of the targeted proteins in the tumor
      cell lines. RESULTS: 2-D WB and mass spectrometry identified citrullinated ENO1
      (alpha-enolase), HSP60 (heat shock protein 60), KRT8 (keratin 8), TUBB (tubulin
      beta), TCRbeta (T cell receptor beta chain), VIME (vimentin) and PDI in these
      cell lines. Immunoprecipitation analyses verified the expression and
      citrullination of ENO1, HSP60, KRT8, and TUBB in the total protein lysates of the
      tumor cell lines. CONCLUSION: The citrullination of proteins ENO1, HSP60, KRT8,
      and TUBB suggests a new mechanism in the tumorigenic process.

PMID- 25975783
TI  - [Effect of platelet derived growth factor-B and its receptor expression on the
      proliferation of renal cell carcinoma ACHN cells].
AB  - OBJECTIVE: To study the effect of platelet derived growth factor-B and its
      receptor expression on the proliferation of renal cell carcinoma ACHN cells in
      vitro and in vivo. METHODS: PDGF-B gene was transfected into human renal
      carcinoma cell line ACHN cells, and the proliferation capability of ACHN cells
      transfected with or without PDGF-B was assessed by MTT assay. The effect of PDGF
      B on the expression of p-PDGFR-beta in endothelial cells and vascular smooth
      muscle cells (VSMC) was detected by Western blot. ACHN cells transfected with
      PDGF-B were injected into mice (untransfected ACHN as control) to induce tumor
      formation. Immunohistochemical staining was used to detect the expression of Ki
      67 in tumor cells and the tumor volume was measured to compare the tumor growth
      in the two groups. RESULTS: The PDGF-B expression of ACHN cells in transfected
      group was significantly increased than that in the untransfected group. MTT assay
      showed that the proliferation capability of ACHN cells in the transfected and
      untransfected groups had no significant differences at different time points
      (P>0.05). The expression of p-PDGFR-beta in VSMC was significantly increased when
      cultured with PDGF-B overexpression culture medium. The mean tumor size of the
      PDGF-B group and control group was (0.305+/-0.108) cm(3) and (0.577+/-0.218)
      cm(3), respectively (P=0.007). Ki-67-positive tumor cells were (41.00+/-5.34)/HPF
      in the PDGF-B-transfected group and (55.80+/-2.95)/HPF in the untransfected group
      (P=0.001). CONCLUSION: PDGF-B overexpression may up-regulate p-PDGFR-beta
      expression of VSMC in renal cell carcinoma, and inhibit the tumor cell
      proliferation and tumor growth through paracrine signaling.

PMID- 25975784
TI  - [Effect and mechanism of Vav3 on the proliferation of human gastric cancer
      SGC7901 cells].
AB  - OBJECTIVE: The purpose of this study was to investigate the effect and mechanism
      of Vav3 gene on the proliferation of human gastric cancer cell line SGC7901.
      METHODS: The expressions of Vav3 proten in gastric cancer tissue, tumor-adjacent
      tissue, human gastric cancer cell line SGC7901 and gastric epithelial cell line
      GES-1 cells were tested by Western blot. Vav3-siRNA was transfected into the
      SGC7901 cells. The proliferation of SGC7901 cells in vitro was measured by MTT
      assay. Cell cycle of SGC7901 cells was determined by flow cytometry.The
      expressions of proliferation-related genes PCNA, p16, cyclin D1, Rb were
      determined by qPCR and Western blot assay. Orthotopic transplantation nude mouse
      models of gastric cancer were prepared, and the tumor growth and expressions of
      PCNA, P16, cyclin D1, and Rb proteins were examined. RESULTS: The relative
      expressions of Vav3 in the gastric cancer and peritumoral tissue were 0.910+/
      0.242 and 0.243+/-0.045, respectively; the relative expressions of Vav3 in
      SGC7901 and GSE-1 cells were 0.925+/-0.127 and 0.277+/-0.038, respevtively (both
      P<0.05). The expression of Vav3 protein in SGC7901 cells was effectively
      inhibited by Vav3-siRNA. Proliferation of SGC7901 cells was inhibited by (83.43+/
      10.17)% after 80 nmol/L Vav3-siRNA transfection (P<0.05). The ratio of SGC7901
      cells in G0/G1 phase was increased, and in S phase decreased after Vav3-siRNA
      transfection (both P<0.05). The expressions of PCNA and cyclin D1 were decreased
      in cells after Vav3-siRNA transfection, and expressions of p16 and Rb were
      increased after Vav3-siRNA transfection (P<0.05 for all). The tumor growth in the
      Vav3-siRNA group was much slower than that in the other 2 control groups of nude
      mouse models. Compared with the two control groups, expressions of PCNA and
      cyclin D1 were significantly lower in the Vav3-siRNA group, while expressions of
      p16 and Rb were increased (P<0.05 for all). CONCLUSION: Vav3 can promote the
      proliferation of gastric cancer cells by regulating proliferation-related genes.

PMID- 25975785
TI  - [CT and MR findings of retroperitoneal ectopic pheochromocytoma].
AB  - OBJECTIVE: To evaluate the CT and MR findings of retroperitoneal ectopic
      pheochromocytoma. METHODS: To analyze retrospectively the CT and MR images of 32
      patients with retroperitoneal ectopic pheochromocytoma proved by pathology.
      RESULTS: The lesions (benign=28, malignant=4) were located in the anterior
      pararenal space (ARS) (n=12), the perirenal space (PS) (n=13) and the posterior
      pararenal space (PRS) (n=7). The tumors showed heterogeneous density on
      unenhanced CT (n=25). Among the 23 cases with enhanced CT imaging, 19 cases had
      marked contrast and 4 had mild contrast. The enhancement patterns included whole
      enhancement (n=9), solid area enhancement (n=12), peripheral enhancement (n=1),
      and spotted enhancement (n=1). The tumors had heterogeneous signal on unenhanced
      MR (n=23), and usually showed enhancement at arterial, portal and delayed phases
      on 22 enhanced MR, while cystic area with no enhancement. The lesions usually had
      cystic changes (n=18), septa (n=16), vessels inside (n=9), hemorrhage (n=3), and
      calcification (n=3). Besides that the morphology had statistical significance
      (P=0.013), other indexes had no statistical significance (P>0.05) in differential
      diagnosis of benign and malignant retroperitoneal ectopic pheochromocytomas.
      CONCLUSIONS: Retroperitoneal ectopic pheochromocytomas have some CT and MR
      features, usually revealed as an oval mass, growing along the paravertebral axis,
      and often with cystic changes. Those signs combined with hypertension and
      elevated catecholamine level may lead to a correct diagnosis.

PMID- 25975786
TI  - [Initial comparison of regional ischemic preconditioning and hemi-hepatic
      vascular inflow occlusion in resection of hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate preliminarily the clinical efficacy of two types of
      hepatic inflow occlusion in hepatectomy for hepatocellular carcinoma (HCC).
      METHODS: A total of 54 patients with HCC who underwent hepatectomy were divided
      into two groups: RIP group (regional ischemic preconditioning with continuous
      clamping, n=15) and HHV group (hemi-hepatic vascular inflow occlusion, n=39). HHV
      was performed by placing a clamp on the right hepatic artery and right portal
      vein, and was maintained until the liver resection was completed. In the RIP
      group, HHV was preceded by a 5-min period of ischemia followed by 5 min of
      reperfusion. The clinical indicators of the two groups were compared. RESULTS:
      The volume of intraoperative blood loss had significant difference between the
      two groups (P=0.039). One case (6.7%) in the RIP group and 17 cases (43.6%) in
      the HHV group received postoperative blood transfusion, showing a significant
      difference (P=0.010). No postoperative 30-day mortality happened in all patients.
      No significant differences were found between the two groups in hospital stay or
      postoperative morbidity, including hepatic insufficiency, infection, ascites,
      pleural effusion, cardiopulmonary complications and intestinal ventilation time
      (P>0.05 for all).The RIP group had a significantly higher PTA level at
      postoperative days 3 and 5 (P<0.001). Although no significant differences were
      found between the two groups regarding total bilirubin, albumin, prealbumin and
      aminotransferase (P>0.05) during any postoperative stage, the ALT recovered to
      normal level in 5 patients (33.3%) of the RIP group and only in one case (2.7%)
      of the HHV group, with a significant difference between the two groups (P=0.006).
      CONCLUSION: The results of this study indicate that regional ischemic
      preconditioning may have better hemostatic effect on hepatectomy, can reduce
      postoperative blood transfusion and promote early recovery of liver function than
      hemi-hepatic vascular inflow occlusion.

PMID- 25975787
TI  - [Comparison of the predictive value of the sixth and seventh edition TNM pT
      classifications in prognosis for gastric cancer].
AB  - OBJECTIVE: To analyze the clinical application value of the 7th edition UICC-AJCC
      TNM pT classification of gastric cancer. METHODS: The classification of tumor
      invasion depth of 874 cases of gastric cancer was determined using the 7th
      edition UICC-AJCC TNM classification and the relationships of prognosis with
      clinicopathological factors was compared with that obtained using the 6th edition
      TNM classification. RESULTS: The 5-year survival rates according to the 6th
      edition pT1, pT2, pT3, pT4 were 98.4%, 55.8%, 26.0% and 24.5%, respectively,
      showing a significant difference among the four substages (P<0.001). The 5-year
      survival rates according to the 7th edition pT1a, pT1b, pT2, pT3, pT4a, and pT4b
      were 98.6%, 98.2%, 75.8%, 48.9%, 26.0% and 24.5%, respectively, and there were
      significant differences in survival time among the six substages (P<0.001).
      According to the 7th edition TNM classification, for the pT2 and pT3 patients
      groups, the 5-year survival rates of the 7th edition pN0 (without lymphatic
      metastasis) were 84.8% and 77.9%, respectively, showing no significant difference
      between the two survival rates (P=0.204). The 5-year survival rates according to
      the 7th edition pNx (with lymphatic metastasis) were 66.9% and 37.5%,
      respectively, and there was a significant difference between the two survival
      times (P<0.001). In multivariate analysis, the 7th edition pT stage, vascular or
      lymphatic invasion, the 6th edition pT staging and primary tumor site were
      independent prognostic factors in patients with gastric cancer (P<0.05), and the
      relationship of the staging of the 7th version of pT was more close with the
      prognosis of patients with gastric carcinoma than that of the 6th edition of pT
      staging system. CONCLUSION: The 7th edition UICC-AJCC classification of pT
      staging of gastric cancer patients has a better prognostic predictive value than
      the 6th edition.

PMID- 25975788
TI  - [Impact of stages of axillary lymph nodes and pathological response to
      neoadjuvant chemotherapy on the survival of breast cancer patients].
AB  - OBJECTIVE: To analyze the relevance between lymph node status and pathological
      response after neoadjuvant chemotherapy and survival in breast cancer patients.
      METHODS: The clinicopathological data of 653 needle biopsy proved breast cancer
      patients, who underwent neoadjuvant chemotherapy and surgery in our hospital from
      July 1998 to April 2012, were retrospective analyzed. RESULTS: The median follow
      up time was 59.3 months. The 653 cases were classified into ypN0 (242 cases),
      ypN1 (182 cases), ypN2 (135 cases), and ypN3 (94 cases) stages, and the 5-year
      overall survival rates in the four groups were 93.4%, 93.4%, 87.4%, and 83.0%,
      respectively. The Log rank test showed a significant difference in the overall
      survival rates between the ypN0, ypN1, ypN2 stages and ypN3 stage (P=0.046). No
      significant differences were observed between the disease free survival (DFS)
      rates in the four groups (P>0.05). Multivariate analysis indicated that the
      postoperative pathological response of metastatic lymph nodes was a major
      prognostic factor affecting the overall survival and disease-free survival
      (RR=1.051, P=0.007; RR=1.028, P=0.028). CONCLUSION: The stage and pathological
      response of axillary lymph nodes after neoadjuvant chemotherapy are effective
      indicators for predicting the OS and DFS in breast cancer patients.

PMID- 25975789
TI  - [Impact of overweight on postoperative complications and oncological outcome
      after radical hepatectomy for metastatic colorectal cancer].
AB  - OBJECTIVE: To evaluate the correlation between overweight and postoperative
      complications and prognosis after radical hepatectomy for colorectal liver
      metastasis (CRLM). METHODS: A total of 192 patients who underwent hepatectomy for
      colorectal liver metastases between January 2000 and March 2012 were eligible for
      the study. We retrospectively summarized their clinicopathological data, BMI
      index and postoperative complications, and investigated the relation between
      these data and complications and prognosis. RESULTS: Of the 192 patients, 109
      cases were classified as overweight with a BMI >=24 and 83 patients were
      classified as non-overweight with a BMI <24. Seventy-five complications occurred
      in 68 of the 192 patients (35.4%) who underwent hepatectomy. Surgical
      complications (P=0.428), operation time (P=0.837), and blood loss (P=0.272) were
      not statistically significantly associated with BMI. 173 patients were included
      to analyze the influence of overweight on oncologic outcome. The median survival
      for the overweight patients was 59 months, while that of non-overweight patients
      was 31 months (P=0.016). The overweight patients had a longer OS assessed by both
      univariate analysis (P=0.016) and multivariate analysis (P=0.031). However, no
      statistical differences in disease-free survival (DFS) were detected between the
      overweight and non-overweight groups (P=0.058). CONCLUSIONS: Overweight is not
      independently associated with an increasing complication rate. BMI does not
      significantly affect the CRLM-DFS, and high BMI patients might have a better
      overall survival.

PMID- 25975790
TI  - [Neoadjuvant chemotherapy using epirubicin, cyclophosphamide and fluorouracil:
      neutropenia and elevation of transaminase, and their management].
AB  - OBJECTIVE: To retrospectively investigate the incidence of severe neutropenia and
      elevation of transaminase during neoadjuvant chemotherapy using epirubicin,
      cyclophosphamide and fluorouracil in breast cancer patients. METHODS: From
      January 2011 to December 2012, 303 consecutive breast cancer patients with
      complete treatment data treated in our department were included in this analysis.
      All patients received neoadjuvant chemotherapy with equal dose of EPI (100
      mg/m(2)) administered every 3 weeks for 4 cycles before surgery. RESULTS: 200
      patients (66.0%) experienced at least one episode of grade 3/4
      neutropenia/leukopenia, among them 176 patients experienced their first episode
      after the first cycle. Febrile neutropenia (FN) occurred in 13 patients for 14
      episodes. Elevation of transaminase occurred in a total of 46 patients (15.2%),
      among them, grade 2 or higher elevation occurred in 15 patients (5.0%). Three
      blood test plans were adopted to monitor the patients during chemotherapy: (1)
      Routine blood count repeated every week; (2) Routine blood count before and on
      day 10 of each chemotherapy episode; (3) Routine blood count before and on day 7,
      10 and 14 of each chemotherapy episode. The number of patients whose chemotherapy
      was delayed due to 3/4 neutropenia/leucopenia in each blood test plan was 3
      (5.0%), 7 (3.9%) and 2 (3.2%), respectively. The number of patients with febrile
      neutropenia (FN) in each blood test plan was 2 (3.3%), 8 (4.4%) and 3 (4.8%),
      respectively. No statistically significant difference in treatment delay or the
      incidence of FN was observed among different blood test plans. No statistically
      significant difference in the incidence of grade 3/4 neutropenia/leukopenia or
      grade 2 or higher transaminase elevation was observed among different 5-Fu
      regimens. CONCLUSIONS: During neoadjuvant chemotherapy using FE100 C, Fci E100 C
      or E100 C for breast cancer patients without routine prophylactic G-CSF, the
      incidence of grade 3/4 neutropenia/leukopenia is 66.0%. With the patient
      management plan we adopted, 4.3% of patients developed febrile neutropenia.
      Prophylactic medication may not be necessary for patients without evident liver
      dysfunction.

PMID- 25975791
TI  - [Value of quantitative iodine-based material decomposition images with gemstone
      spectral CT imaging in the follow-up of patients with hepatocellular carcinoma
      after TACE treatment].
AB  - OBJECTIVE: To investigate the value of quantitative iodine-based material
      decomposition images with gemstone spectral CT imaging in the follow-up of
      patients with hepatocellular carcinoma (HCC) after transcatheter arterial
      chemoebolization (TACE). METHODS: Consecutive 32 HCC patients with previous TACE
      treatment were included in this study. For the follow-up, arterial phase (AP) and
      venous phase (VP) dual-phase CT scans were performed with a single-source dual
      energy CT scanner (Discovery CT 750HD, GE Healthcare). Iodine concentrations were
      derived from iodine-based material-decomposition images in the liver parenchyma,
      tumors and coagulation necrosis (CN) areas. The iodine concentration difference
      (ICD) between the arterial-phase (AP) and venal-phase (VP) were quantitatively
      evaluated in different tissues.The lesion-to-normal parenchyma iodine
      concentration ratio (LNR) was calculated. ROC analysis was performed for the
      qualitative evaluation, and the area under ROC (Az) was calculated to represent
      the diagnostic ability of ICD and LNR. RESULTS: In all the 32 HCC patients, the
      region of interesting (ROI) for iodine concentrations included liver parenchyma
      (n=42), tumors (n=28) and coagulation necrosis (n=24). During the AP the iodine
      concentration of CNs (median value 0.088 ug/mm(3)) appeared significantly higher
      than that of the tumors (0.064 ug/mm(3), P=0.022) and liver parenchyma (0.048
      ug/mm(3), P=0.005). But it showed no significant difference between liver
      parenchyma and tumors (P=0.454). During the VP the iodine concentration in
      hepatic parenchyma (median value 0.181 ug/mm(3)) was significantly higher than
      that in CNs (0.140 ug/mm(3), P=0.042). There was no significant difference
      between liver parenchyma and tumors, CNs and tumors (both P>0.05). The median
      value of ICD in CNs was 0.006 ug/mm(3), significantly lower than that of the HCC
      (0.201 ug/mm(3), P<0.001) and hepatic parenchyma (0.117 ug/mm(3), P<0.001). The
      ICDs in tumors and hepatic parenchyma showed no significant difference (P=0.829).
      During the AP, the LNR had no significant difference between CNs and tumors (a
      median value 1.805 vs. 1.310, P=0.389), and during the VP, the difference was
      also non-significant (the median value 0.647 vs. 0.713, P=0.660). The mean Az
      value of ICDs for evaluation of surviving tumor tissues was 0.804, whiles LNR
      measured a disappointing result in both AV images and VP images. CONCLUSION:
      Quantitative iodine-based material decomposition images with gemstone spectral CT
      imaging can improve the diagnostic efficacy of CT imaging for HCC patients after
      TACE treatment.

PMID- 25975792
TI  - [Value of FDG PET-CT associated with pathology in diagnosing residual tumor in
      patients with nasopharyngeal carcinoma after radiotherapy].
AB  - OBJECTIVE: To find a rational way in early detecting the residual tumor in
      patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: A total
      of 47 NPC patients who were diagnosed residual tumor after radiotherapy and
      treated in our hospital from Dec 2009 to Aug 2012 were included in this study and
      their clinicopathological and follow-up data were reviewed and analyzed. The
      patients were checked by nasopharynx MRI, FDG PET-CT and were examined by biopsy
      of the residual tumors within two weeks after radiotherapy. The diagnosis of
      relapses was determined by pathological re-examination. RESULTS: All the 47
      patients were followed up for 10-42 months. Three of them had nasopharynx
      relapse. The others had not tumor relapse and their residual tumors disappeared
      completely. The specificity of MRI, FDG PET-CT and pathological tumor response in
      diagnosing residual tumors were 9.1%, 77.3%, and 95.5% (P<0.001). Their accuracy
      rates were 14.9%, 78.9%, and 95.7%, respectively (P<0.001). The M of SUVmax in
      the team who had moderate and severe pathologic tumor response (team A) was 3.05
      and that in the team who had mild pathologic tumor response (team B) was 4.68
      (P=0.012). None of patients in the team A had nasopharynx relapse. Three patients
      in the team B who had SUVmax >=4 had nasopharynx relapses, and in other 2
      patients who had SUVmax <4, the residual tumors disappeared during the following
      up. The specificity and accuracy in diagnosing residual tumors were increased
      when mild pathologic tumor response combined with SUVmax4 were used. CONCLUSION:
      PET-CT combined with pathologic tumor response is beneficial for early diagnosis
      of residual nasopharyngeal tumors after radiotherapy.

PMID- 25975793
TI  - [Prognostic analysis of nasopharyngeal carcinoma patients with distant metastasis
      after curative radiotherapy].
AB  - OBJECTIVE: To analyze the prognosis and its influencing factors for
      nasopharyngeal carcinoma patients with distant metastasis after radical
      radiotherapy. METHODS: Clinical data of 184 cases of nasopharyngeal carcinoma
      after radical radiotherapy with distant metastases were retrospectively reviewed
      and the factors affecting prognosis were analyzed. RESULTS: The median survival
      time was 12 months for the whole group, and the 1-, 2-, and 3-year survival rates
      were 50.6%, 30.7% and 20.9%, respectively. Cox univariate analysis showed that
      the prognosis of patients with metastasis after radiotherapy was significantly
      related with The N stage, chemotherapy, time interval between the end of
      radiotherapy and occurrence of distant metastasis, metastatic sites, chemotherapy
      after metastasis, cycles of chemotherapy and palliative radiotherapy after
      metastasis (P<0.05), but not significantly related with sex, age, T stage,
      clinical stage, cycles of chemotherapy, radiation technique and radiation dose
      for initial treatment (P>0.05). Advanced N stage, no chemotherapy, short time
      interval between the end of radiotherapy and occurrence of distant metastasis,
      multiple metastases, no radiotherapy or chemotherapy for metastases were
      predictive for poor prognosis (P<0.05). Multivariable analysis indicated that
      factors including N stage at initial diagnosis, metastatic sites, whether or not
      chemotherapy was given, the time interval between the end of radiotherapy and the
      occurrence of distant metastasis were independent factors affecting the prognosis
      of nasopharyngeal carcinoma patients with distant metastasis after radiotherapy.
      CONCLUSIONS: N stage at initial diagnosis, metastatic sites, whether or not
      chemotherapy was given, the time interval between the end of radiotherapy and the
      occurrence of distant metastasis are independent factors affecting the prognosis
      for nasopharyngeal carcinoma patients with distant metastasis after radiotherapy.
      Systemic chemotherapy and local palliative radiotherapy are the primary treatment
      for nasopharyngeal carcinoma patients with metastasis.

PMID- 25975794
TI  - [Clinical outcomes and prognostic factors in limited-stage small cell lung
      cancer: a single institution experience].
AB  - OBJECTIVE: To evaluate the effect of comprehensive treatment and examine the
      impact of clinical factors on the survival outcome of limited-stage small cell
      lung cancer. METHODS: The clinical records of 335 patients with limited-stage
      small cell lung cancer treated in the Cancer Hospital of Chinese Academy of
      Medical Sciences between January 1996 and December 2006 were analyzed
      retrospectively in this study. Kaplan-Meier method was used for survival
      analysis, and log-rank test and Cox regression were used for univariate and
      multivariate analyses of prognostic factors. RESULTS: The median follow-up time
      was 54 months for all patients, the median survival time was 23.8 months, and
      progression-free survival was 12.5 months. The 2-, 3-, and 5-year overall
      survival rates were 47.3%, 32.9%, and 22.9%, respectively. The acute toxicity
      during comprehensive treatment was tolerable. The incidence of >=grade 3
      hematological toxicity, >=grade 3 gastrointestinal toxicity, >=grade 2 radiation
      pneumonitis and >=grade 2 acute esophagitis were 37.0%, 14.9%, 11.0%, and 38.8%,
      respectively. The univariate analysis showed that KPS<80, smoking and high LDH
      level significantly reduced the overall survival time in patients with limited
      stage SCLC. The multivariate analysis showed that KPS and weight loss were
      independent factors affecting the prognosis for the limited stage SCLC patients
      (P<0.05 for all). CONCLUSIONS: Sequential chemoradiotherapy can be safely and
      effectively performed in limited-stage small cell lung cancer. Krnofsky
      performance status and weight loss are independent prognostic factors for the
      overall survival of LS-SCLC.

PMID- 25975795
TI  - [Small-cell neuroendocrine carcinoma of the stomach: a clinical and prognostic
      analysis of 21 cases].
AB  - OBJECTIVE: To investigate and improve the diagnosis and management of small-cell
      neuroendocrine carcinoma of the stomach (SCNECS). METHODS: The
      clinicopathological information and survival data of 21 cases of SCNECS treated
      in our hospital from January 2003 to December 2012 were analyzed retrospectively.
      RESULTS: The median survival time of the 21 cases was (12.1+/-1.6) months. The 1
      year overall survival rate of the patients was 33.3%. Univariate analysis showed
      that the risk factors of survival were tumor size, lymph node status, tumor
      stage, treatment and radical operation or not (P<0.05 for all). Multivariate
      analysis indicated that independent risk factors were tumor size >=4.6 cm, lymph
      node metastasis and tumor stage III/IV (P<0.05 for all). Radical operation and
      comprehensive treatment (surgery + postoperative chemotherapy) were independent
      protective factors (all P<0.05). CONCLUSIONS: SCNECS is a rare malignant tumor
      with early metastasis and poor prognosis. Tumor size, stage, lymph node status,
      and treatment have potential impact on the prognosis. Comprehensive treatment
      based on radical operation may improve the survival of SCNECS patients.

PMID- 25975796
TI  - [Clinicopathologic features and prognosis of 51 patients with alpha-fetoprotein
      producing gastric cancer].
AB  - OBJECTIVE: To analyze the clinicopathologic features and prognosis of alpha
      fetoprotein (AFP)-producing gastric cancers (AFPGC). METHODS: Fifty-one serum AFP
      positive patients with positive immunohistochemical staining of AFP in the
      primary lesions (study group) and sixty-five gastric cancer cases with normal AFP
      level (control group) treated in our department from January 2005 to December
      2007 were included in this study. Their clinicopathologic features and follow-up
      data were statistically analyzed. RESULTS: Compared with the control group, the
      study group had a higher incidence of poorly differentiated adenocarcinoma
      (P=0.021) and liver metastasis (P=0.001) than that in the control group.The TNM
      stages in the study group were significantly higher than those in the control
      group (P=0.001). The 1-, 2-, and 5-year survival rates of the study group were
      62.7%, 27.5% and 4.7%, respectively, and the median survival was 16 months,
      significantly lower than the 84.6%, 55.4%, 16.5%, and 30 months of the control
      group (P<0.001 for all). The serum AFP levels in the study group ranged from
      58.63 ug/L to 12 100.00 ug/L, and could be classified into two groups:27 cases
      <500 ug/L, and 24 cases >=500 ug/L. There was no significant difference of the
      immunohistochemical staining results between the two subgroups (P=0.912).
      CONCLUSIONS: AFPGC is a special type of gastric cancer with high degree of
      malignancy and poor prognosis. Monitoring of serum AFP level can earlier detect
      the progression of disease and give corresponding treatment.

PMID- 25975797
TI  - [Consideration on the design of early phase clinical trial of new anticancer
      drugs].

PMID- 25975798
TI  - Informing Tobacco Cessation Benefit Use Interventions for Unionized Blue-Collar
      Workers: A Mixed-Methods Reasoned Action Approach.
AB  - Blue-collar workers typically have high rates of tobacco use but low rates of
      using tobacco cessation resources available through their health benefits.
      Interventions to motivate blue-collar tobacco users to use effective cessation
      support are needed. Reasoned action theory is useful in this regard as it can
      identify the beliefs that shape tobacco cessation benefit use intentions.
      However, conventional reasoned action research cannot speak to how those beliefs
      can best be translated into intervention messages. In the present work, we expand
      the reasoned action approach by adding additional qualitative inquiry to better
      understand blue-collar smokers' beliefs about cessation benefit use. Across three
      samples of unionized blue-collar tobacco users, we identified (1) the 35
      attitudinal, normative, and control beliefs that represented tobacco users'
      belief structure about cessation benefit use; (2) instrumental attitude as most
      important in explaining cessation intention; (3) attitudinal beliefs about
      treatment options' efficacy, health effects, and monetary implications of using
      benefits as candidates for message design; (4) multiple interpretations of
      cessation beliefs (e.g., short and long-term health effects); and (5) clear
      implications of these interpretations for creative message design. Taken
      together, the findings demonstrate how a mixed-method reasoned action approach
      can inform interventions that promote the use of tobacco cessation health
      benefits.

PMID- 25975801
TI  - Bone Marrow-Derived Mesenchymal Stem Cells Improve Diabetic Neuropathy by Direct
      Modulation of Both Angiogenesis and Myelination in Peripheral Nerves.
AB  - Recent evidence has suggested that diabetic neuropathy (DN) is
      pathophysiologically related to both impaired angiogenesis and a deficiency of
      neurotrophic factors in the nerves. It is widely known that vascular and neural
      growths are intimately associated. Mesenchymal stem cells (MSCs) promote
      angiogenesis in ischemic diseases and have neuroprotective effects, particularly
      on Schwann cells. Accordingly, we investigated whether DN could be improved by
      local transplantation of MSCs by augmenting angiogenesis and neural regeneration
      such as remyelination. In sciatic nerves of streptozotocin (STZ)-induced diabetic
      rats, motor and sensory nerve conduction velocities (NCVs) and capillary density
      were reduced, and axonal atrophy and demyelination were observed. After injection
      of bone marrow-derived MSCs (BM-MSCs) into hindlimb muscles, NCVs were restored
      to near-normal levels. Histological examination demonstrated that injected MSCs
      were preferentially and durably engrafted in the sciatic nerves, and a portion of
      the engrafted MSCs were distinctively localized close to vasa nervora of sciatic
      nerves. Furthermore, vasa nervora increased in density, and the ultrastructure of
      myelinated fibers in nerves was observed to be restored. Real-time RT-PCR
      experiments showed that gene expression of multiple factors involved in
      angiogenesis, neural function, and myelination were increased in the MSC-injected
      nerves. These findings suggest that MSC transplantation improved DN through
      direct peripheral nerve angiogenesis, neurotrophic effects, and restoration of
      myelination. 

PMID- 25975802
TI  - Sleep apnea and severe bradyarrhythmia--an alternative treatment option: a case
      report.
AB  - INTRODUCTION: Sinus arrest, atrio-ventricular block, supraventricular, and
      ventricular arrhythmias have been reported in patients with sleep apnea syndrome.
      The arrhythmias usually occur during sleep and contribute to the cardiovascular
      morbidity and mortality, and the treatment of sleep apnea usually results in the
      resolution of the brady- arrhythmias. Weight loss, continuous positive airway
      pressure (CPAP), oral appliances, and upper airway surgery are the recommended
      treatments, however, compliance and efficacy are issues. CASE PRESENTATION: A 58
      year-old Arab man presented with recurrent presyncope. He was subsequently
      diagnosed with sleep apnea associated with frequent and significant sinus pauses.
      He presented a treatment challenge because he refused continuous positive airway
      pressure and pacemaker, however, he was successfully treated with theophylline.
      CONCLUSION: Frequent and significant sinus pause associated with sleep apnea was
      successfully treated with theophylline in our patient when the standard treatment
      of care was refused.

PMID- 25975803
TI  - Design and synthesis of new fluconazole analogues.
AB  - We have synthesized new fluconazole analogues containing two different 1,2,3
      triazole units in the side chain. The synthesis of new amide analogues using a
      variety of acids is also described. All the compounds showed very good antifungal
      activity. A hemolysis study of the most active compounds 6e and 13j showed that
      both compounds did not cause any hemolysis at the dilutions tested. These
      compounds did not exhibit any toxicity to L929 cells at MIC and lower
      concentrations. In the docking study, the overall binding mode of 6e and 13j
      appeared to be reasonable and provided a good insight into the structural basis
      of inhibition of Candida albicans Cyp51 by these compounds. 

PMID- 25975804
TI  - Potential rapid evolution of foot morphology in Italian plethodontid salamanders
      (Hydromantes strinatii) following the colonization of an artificial cave.
AB  - How organisms respond to environmental change is a long-standing question in
      evolutionary biology. Species invading novel habitats provide an opportunity to
      examine contemporary evolution in action and decipher the pace of evolutionary
      change over short timescales. Here, we characterized phenotypic evolution in the
      Italian plethodontid salamander, Hydromantes strinatii, following the recent
      colonization of an artificial cave by a forest floor population. When compared
      with a nearby and genetically related population in the natural forest floor and
      a nearby cave population, the artificial cave population displayed significant
      differences in overall foot shape, with more interdigital webbing relative to the
      other populations. Further, this population evolved significantly larger feet,
      which corresponded more closely to those found in other cave populations than to
      forest floor populations to which the cave population is closely related.
      Finally, we quantified the rate of evolution for both foot shape and foot area,
      and found that both traits displayed large and significant evolutionary rates, at
      levels corresponding to other classic cases of rapid evolution in vertebrates.
      Together, these findings reveal that the response to novel environmental
      pressures can be large and rapid and that the anatomical shifts observed in the
      artificial cave population of H. strinatii may represent a case of rapid
      evolution in response to novel environmental pressures.

PMID- 25975805
TI  - Submicrometer Imaging by Laser Ablation-Inductively Coupled Plasma Mass
      Spectrometry via Signal and Image Deconvolution Approaches.
AB  - In this work, pre- and postacquisition procedures for enhancing the lateral
      resolution of laser ablation-inductively coupled plasma mass spectrometry (LA
      ICPMS) in two- and three-dimensional (2D, 3D) nuclide distribution mapping beyond
      the laser beam waist are described. 2D images were constructed by projecting a
      rectangular grid of discrete LA positions, arranged at interspacings smaller than
      the dimensions of the laser beam waist, onto the sample surface, thus
      oversampling the region of interest and producing a 2D image convolved in the
      spatial domain. The pulse response peaks of a low-dispersion LA cell were
      isolated via signal deconvolution of the transient mass analyzer response. A 3D
      stack of 2D images was deconvolved by an iterative Richardson-Lucy algorithm with
      Total Variance regularization, enabling submicrometer image fidelity,
      demonstrated in the analysis of trace level features in corroded glass. A point
      spread function (PSF) could be derived from topography maps of single pulse
      craters from atomic force microscopy. This experimental PSF allows the approach
      to take into account the laser beam shape, beam aberrations, and the laser-solid
      interaction, which in turn enhances the spatial resolution of the reconstructed
      volume. 

PMID- 25975806
TI  - Mobile platform for treatment of stroke: A case study of tele-assistance.
AB  - This article presents the technological solution of a tele-assistance process for
      stroke patients in acute phase in the Seville metropolitan area. The main
      objective of this process is to reduce time from symptom onset to treatment of
      acute phase stroke patients by means of telemedicine, regarding mobility between
      an intensive care unit ambulance and an expert center and activating the pre
      hospital care phase. The technological platform covering the process has been
      defined following an interoperability model based on standards and with a focus
      on service-oriented architecture focus. Messaging definition has been designed
      according to the reference model of the CEN/ISO 13606, messages content follows
      the structure of archetypes. An XDS-b (Cross-Enterprise Document Sharing-b)
      transaction messaging has been designed according to Integrating the Healthcare
      Enterprise profile for archetype notifications and update enquiries.This research
      has been performed by a multidisciplinary group. The Virgen del Rocio University
      Hospital acts as Reference Hospital and the Public Company for Healthcare as
      mobility surroundings.

PMID- 25975807
TI  - Combining transcranial ultrasound with intelligent communication methods to
      enhance the remote assessment and management of stroke patients: Framework for a
      technology demonstrator.
AB  - With over 150,000 strokes in the United Kingdom every year, and more than 1
      million living survivors, stroke is the third most common cause of death and the
      leading cause of severe physical disability among adults. A major challenge in
      administering timely treatment is determining whether the stroke is due to
      vascular blockage (ischaemic) or haemorrhage. For patients with ischaemic stroke,
      thrombolysis (i.e. pharmacological 'clot-busting') can improve outcomes when
      delivered swiftly after onset, and current National Health Service Quality
      Improvement Scotland guidelines are for thrombolytic therapy to be provided to at
      least 80 per cent of eligible patients within 60 min of arrival at hospital.
      Thrombolysis in haemorrhagic stroke could severely compound the brain damage, so
      administration of thrombolytic therapy currently requires near-immediate care in
      a hospital, rapid consultation with a physician and access to imaging services (X
      ray computed tomography or magnetic resonance imaging) and intensive care
      services. This is near impossible in remote and rural areas, and stroke mortality
      rates in Scotland are 50 per cent higher than in London. We here describe our
      current project developing a technology demonstrator with ultrasound imaging
      linked to an intelligent, multi-channel communication device - connecting to
      multiple 2G/3G/4G networks and/or satellites - in order to stream live ultrasound
      images, video and two-way audio streams to hospital-based specialists who can
      guide and advise ambulance clinicians regarding diagnosis. With portable
      ultrasound machines located in ambulances or general practices, use of such
      technology is not confined to stroke, although this is our current focus.
      Ultrasound assessment is useful in many other immediate care situations,
      suggesting potential wider applicability for this remote support system. Although
      our research programme is driven by rural need, the ideas are potentially
      applicable to urban areas where access to imaging and definitive treatment can be
      restricted by a range of operational factors.

PMID- 25975808
TI  - From Juvenile Offender Institutions to Residential Treatment Centers: Evidence of
      the Shifting Paradigm to Improved Youth and Community Outcomes.
AB  - Hundreds of thousands of youth are held every year in U.S. juvenile justice
      detention centers and incarceration facilities. Increasingly it is known that
      these facility placements are at best ineffective and at worst lead to additional
      youth recidivism outcomes. What is most concerning, though, is that a majority of
      these incarcerated youth have one or more mental health/substance abuse
      disorders, special education disabilities, or maltreatment victimization
      histories-comorbid situations that negatively impact their involvement with the
      juvenile courts. In this article the authors summarize the epidemiology of these
      youth problems within the juvenile justice system. The authors then compare the
      outcome evidence for the youth placed in juvenile justice facilities with those
      placed in residential treatment centers, finding significant advantages to
      addressing the problems through rehabilitative efforts. Recognizing that there
      are a small number of serious youthful offenders who will need placement, their
      analysis finds that the juvenile courts must continue (or in many instances
      begin) reshaping their detention and incarceration facilities reliance on
      punishment toward a rehabilitative residential model.

PMID- 25975809
TI  - Healy's editorial on serotonin and depression does a disservice to psychiatrists.

PMID- 25975810
TI  - Analysis of oxidative stress expressed by urinary level of biopyrrins and 8
      hydroxydeoxyguanosine in patients with chronic schizophrenia.
AB  - AIMS: Previous studies have supported the claim that psychological stress induces
      the production of reactive oxygen species. Several authors have suggested that
      patients with psychiatric disorders show high levels of oxidative stress markers.
      We examined different oxidative stress markers in patients with chronic
      schizophrenia. METHODS: This study included 29 patients with chronic
      schizophrenia and 30 healthy volunteers. The concentration of urinary biopyrrins
      and 8-hydroxydeoxyguanosine (8-OHdG), as measured by enzyme-linked immunosorbent
      assay, were normalized to the urinary concentration of creatinine. Psychiatric
      symptoms were assessed by the administration of the Brief Psychiatric Rating
      Scale (BPRS). RESULTS: The concentration of biopyrrins in patients with chronic
      schizophrenia was significantly higher when compared with healthy volunteers. The
      correlation between biopyrrin level and the duration of illness was highly
      significant. There were no significant differences in the levels of urinary 8
      OHdG between the two groups. In schizophrenic patients, the level of urinary
      biopyrrins showed correlations with BPRS scores, while the level of urinary 8
      OHdG did not show correlations with BPRS. CONCLUSIONS: Urinary biopyrrins are
      increased in patients with chronic schizophrenia while urinary 8-OHdG is not
      increased. These findings suggest that patients with chronic schizophrenia are
      under the condition of certain oxidative stresses.

PMID- 25975811
TI  - Successful treatment with Rituximab and Bendamustine in a patient with newly
      diagnosed Waldenstrom's Macroglobulinemia complicated by Bing-Neel syndrome.

PMID- 25975812
TI  - Population pharmacokinetic modeling of quetiapine after administration of
      seroquel and seroquel XR formulations to Western and Chinese patients with
      schizophrenia, schizoaffective disorder, or bipolar disorder.
AB  - A population model describing quetiapine pharmacokinetics (PK) in Western and
      Chinese patients following oral administration of immediate-release (IR) and
      extended-release (XR) formulations was developed using plasma concentrations in
      127 patients from 5 studies with quetiapine IR and/or XR in Western patients and
      1 study with quetiapine XR in Chinese patients. A 1-compartmental model with
      first-order absorption and first-order elimination adequately described the
      quetiapine PK. The typical apparent volume of distribution and elimination rate
      constant of quetiapine were 574 L and 0.12 h(-) (1) , respectively. The estimated
      population absorption rate constants were 1.46 and 0.10 h(-1) for quetiapine IR
      and XR, respectively. Covariate analysis revealed that race was not a significant
      covariate influencing the PK of quetiapine. Simulation conducted with the final
      quetiapine population PK model predicted that the administration of a 200-mg
      twice-daily dose of quetiapine IR in Chinese patients would achieve a steady
      state AUC (AUCss ) +/- standard deviation of 3087 +/- 1480 ng . h/mL, which is in
      close agreement with the reported value (3538 +/- 1728 ng . h/mL). The model also
      predicted that once-daily administration of 300 mg quetiapine IR or XR would
      achieve similar exposure in terms of AUCss in Chinese patients. 

PMID- 25975814
TI  - Energetic 2,2-Dimethyltriazanium Salts: A New Family of Nitrogen-Rich Hydrazine
      Derivatives.
AB  - Amination of 1,1-dimethylhydrazine with NH2 Cl or hydroxylamine-O-sulfonic acid
      yields 2,2-dimethyltriazanium (DMTZ) chloride (3) and sulphate (4), respectively.
      The DMTZ cation was paired with the nitrogen-rich anions 5-aminotetrazolate (5),
      5-nitrotetrazolate (6), 5,5'-azobistetrazolate (7), and azide (8), yielding a new
      family of energetic salts. The synthesis was carried out by metathesis reactions
      of salts 3 or 4 and a suitable silver or barium salt. To minimize the risks
      involved when using heavy metal salts, we used electrodialysis for the synthesis
      of azide 8, which avoids the use of highly sensitive species. The DMTZ
      derivatives were characterized by IR and multinuclear NMR spectroscopy, elemental
      analysis, and X-ray diffraction. Thermal stabilities were measured using DSC
      analysis and their sensitivities towards classical stimuli were determined using
      standard tests. Lastly, the relationship between hydrogen bonding in the solid
      state and sensitivity is discussed. 

PMID- 25975813
TI  - CfLec-3 from scallop: an entrance to non-self recognition mechanism of
      invertebrate C-type lectin.
AB  - A C-type lectin (CfLec-3) from Chlamys farreri with three carbohydrate
      recognition domains (CRDs) was selected to dissect the possible mechanisms of
      PAMP binding and functional differentiation of invertebrate lectins. CfLec-3
      distributed broadly, and its mRNA expression in hemocytes increased significantly
      after stimulations with LPS, PGN or beta-glucan, but not poly(I:C). The
      recombinant CfLec-3 (rCfLec-3) could bind PAMPs and several microbes. rCfLec-3
      mediated hemocytes phagocytosis against Escherichia coli and encapsulation
      towards agarose beads. Obvious functional differentiation occurred among the
      three CRDs, as CRD1 exhibited higher activity to bind PAMPs, while CRD2/3 were
      expert in promoting hemocyte mediated opsonisation. The tertiary structural
      differences were suspected to be associated with such functional differentiation.
      PAMP binding abilities of CfLec-3 were determined by Ca(2+)-binding site 2 motif.
      When Pro in this motif of each CRD was mutated into Ser, their PAMP binding
      abilities were deprived absolutely. rCRD2 acquired mannan binding capability when
      its EPD was replaced by EPN, but lost when EPN in rCRD3 was changed into EPD. The
      Pro in Ca(2+)-binding site 2 was indispensable for PAMPs binding, while Asn was
      determinant for specific binding to mannan. It shed new insight into PAMPs
      binding mechanism of invertebrate C-type lectins and their functional
      differentiation. 

PMID- 25975815
TI  - Identification and Mechanistic Investigation of Drug-Drug Interactions Associated
      With Myopathy: A Translational Approach.
AB  - Myopathy is a group of muscle diseases that can be induced or exacerbated by drug
      drug interactions (DDIs). We sought to identify clinically important myopathic
      DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase
      the risk of myopathy based on analysis of observational data from the Indiana
      Network of Patient Care. Loratadine interacted with simvastatin (relative risk
      95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole
      (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod
      (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to
      result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of
      hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe
      in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a
      role in loratadine-simvastatin interaction. This interaction was
      epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data
      from the US Food and Drug Administration Adverse Event Reporting System.

PMID- 25975817
TI  - Evaluation of the safety profile of Zolafren(r), a generic olanzapine
      formulation, in patients with bipolar disorder: a post-authorization safety
      study.
AB  - INTRODUCTION: Prior to registration, no clinical trial evaluating safety and
      tolerability of Zolafren(r) (Adamed Sp. z o.o., Czosnow, Poland), a generic
      olanzapine formulation, had been performed. Therefore, the aim of this post
      authorization safety study (PASS) was to evaluate the safety and tolerability of
      Zolafren in patients with bipolar disorder (BD). METHODS: Adverse events (AEs)
      associated with the use of Zolafren were recorded in a PASS, in an open-label,
      non-randomized, multicenter observational study involving 20,698 outpatients with
      BD. RESULTS: Zolafren was used in both monotherapy (82.8%) and polytherapy
      (17.2%) at a mean dose of 12.1+/-4.2 mg. The most commonly used formulation was
      coated tablets (70.9%). Orally dissolving tablets (19.7%) and hard capsules
      (9.4%) were less commonly used. During a period of 171+/-47 days of exposure to
      Zolafren, 5883 AEs were reported in 2138 patients (10.3% of the study
      population). None of the reported AEs were severe. Zolafren-associated AEs were
      the reason for discontinuation in 43 patients and the reason for dose reduction
      in a further 762 patients. The most common AE was weight gain (by 1.6+/-3.3 kg)
      which was considered unrelated to the dose of Zolafren. During follow-up, the
      percentage of patients with very good tolerance with Zolafren increased from
      44.4% to 59.8%. The percentage of patients who had confidence in Zolafren also
      increased. CONCLUSION: The results of this PASS support the safety of Zolafren
      use and indicate a high tolerance in patients treated for BD. FUNDING: Adamed Sp.
      z o.o., Czosnow, Poland.

PMID- 25975816
TI  - Absence of Drug-Drug Interactions Between Luseogliflozin, a Sodium-Glucose Co
      transporter-2 Inhibitor, and Various Oral Antidiabetic Drugs in Healthy Japanese
      Males.
AB  - INTRODUCTION: We investigated the possibilities of drug-drug interactions between
      luseogliflozin, a sodium-glucose co-transporter-2 inhibitor, and oral
      antidiabetic drugs (OADs) in healthy Japanese males. METHODS: We conducted six
      independent studies to investigate potential drug-drug interactions between 5 mg
      luseogliflozin and the following OADs usually used in Japan: 1 mg glimepiride,
      250 mg metformin, 30 mg pioglitazone, 50 mg sitagliptin, 50 mg miglitol, or 0.6
      mg voglibose (0.2 mg before each meal). Twelve subjects were enrolled in each
      study. The glimepiride, metformin, sitagliptin, and miglitol studies were
      randomized, open-label, single-dose, three-way crossover studies. The
      pioglitazone and voglibose studies were open-label studies, where a single dose
      of luseogliflozin was added to multiple doses of pioglitazone or voglibose. The
      endpoints were the area under the curve from 0 to 24 h (AUC0-24 h) or to infinity
      (AUCinf) and the maximum concentration (Cmax) of each drug administered alone or
      in combination. RESULTS: The 90% confidence intervals (CIs) of the geometric mean
      ratio (GMR) for Cmax of luseogliflozin in the pioglitazone and miglitol studies
      were beyond the reference range for bioequivalence (0.80-1.25) (miglitol: 0.851
      [0.761, 0.952]; pioglitazone: 1.16 [1.04, 1.30]). However, the 90% CIs for AUC0
      24 h were within the reference range. The 90% CIs of the GMRs for Cmax and AUC0
      24 h of pioglitazone were beyond the reference range (Cmax 0.884 [0.746, 1.05];
      AUC0-24 h 0.896 [0.774, 1.04]), but the 90% CIs for the active metabolites of
      pioglitazone were within the reference range. For the other combinations tested,
      the 90% CIs and GMRs for luseogliflozin and the individual OADs were within the
      reference range. CONCLUSION: No clinically meaningful interactions were observed
      between luseogliflozin and six commonly used OADs in Japan, although there were
      some changes in the pharmacokinetics of pioglitazone co-administered with
      luseogliflozin and for luseogliflozin co-administered with miglitol or
      pioglitazone. FUNDING: Taisho Pharmaceutical Co., Ltd.

PMID- 25975818
TI  - Neuroprotection after major cardiovascular surgery.
AB  - OPINION STATEMENT: Neurologic injury is a common complication of major
      cardiovascular procedures including coronary artery bypass graft (CABG) surgery,
      coronary valve replacement, and aortic aneurysm surgery. However, despite ongoing
      research in the field of neuroprotection, there are currently few pharmacologic
      and interventional options to effectively protect the brain and spinal cord in
      the postoperative period. CSF drainage after aortic surgery currently stands as
      the only neuroprotective intervention that has been consistently shown to protect
      the spinal cord from ischemic injury, leading to significantly fewer patients
      with paraplegia and paraparesis. There is promising but conflicting evidence
      about the potential benefits of agents such as dexmedetomidine, lidocaine,
      magnesium, and erythropoietin in preventing postoperative stroke and cognitive
      dysfunction. Postoperative hypothermia has also been studied in preventing
      neurologic injury after cardiopulmonary bypass. With the rate of cardiovascular
      surgeries increasing yearly, further investigations are needed to validate many
      of these therapies and discover new ways to protect the brain and spinal cord
      from intraoperative and postoperative injuries in this high-risk population.

PMID- 25975819
TI  - Antiangiogenic treatment of meningiomas.
AB  - OPINION STATEMENT: Meningiomas are the most common intracranial tumors and the
      majority of cases is curable by surgical resection. Incompletely resected tumors
      and tumors with signs of increased malignancy (WHO grade II and III tumors) are
      prone to recur. In meningiomas relapsing after surgical resection and after
      exhaustion of radiotherapeutic options, drug therapy is to be considered. A
      variety of drugs has been studied in meningiomas, including hydroxyurea,
      temozolomide, irinotecan, interferon-alpha, mifepristone, octreotide analogues,
      megestrol acetate, bevacizumab, sunitinib, vatalinib, imatinib, erlotinib, and
      gefitinib. Unfortunately, most of these agents have shown no or very limited
      activity against meningiomas and cannot be recommended for clinical use.
      Compounds with antiangiogenic properties, i.e., bevacizumab, sunitinib, and
      vatalinib have shown potential efficacy in uncontrolled studies and should be
      investigated further, ideally in randomized clinical trials. Emerging clinical
      studies will evaluate novel medical treatment approaches including the tetra
      hydroisoquinoline alkaloid trabectedin (European Organisation for Research and
      Treatment of Cancer (EORTC) phase II trial 1320) and SMO or AKT inhibitors in
      molecularly selected cases.

PMID- 25975820
TI  - Stimulus-dependent differences in signalling regulate epithelial-mesenchymal
      plasticity and change the effects of drugs in breast cancer cell lines.
AB  - INTRODUCTION: The normal process of epithelial mesenchymal transition (EMT) is
      subverted by carcinoma cells to facilitate metastatic spread. Cancer cells rarely
      undergo a full conversion to the mesenchymal phenotype, and instead adopt
      positions along the epithelial-mesenchymal axis, a propensity we refer to as
      epithelial mesenchymal plasticity (EMP). EMP is associated with increased risk of
      metastasis in breast cancer and consequent poor prognosis. Drivers towards the
      mesenchymal state in malignant cells include growth factor stimulation or
      exposure to hypoxic conditions. METHODS: We have examined EMP in two cell line
      models of breast cancer: the PMC42 system (PMC42-ET and PMC42-LA sublines) and
      MDA-MB-468 cells. Transition to a mesenchymal phenotype was induced across all
      three cell lines using epidermal growth factor (EGF) stimulation, and in MDA-MB
      468 cells by hypoxia. We used RNA sequencing to identify gene expression changes
      that occur as cells transition to a more-mesenchymal phenotype, and identified
      the cell signalling pathways regulated across these experimental systems. We then
      used inhibitors to modulate signalling through these pathways, verifying the
      conclusions of our transcriptomic analysis. RESULTS: We found that EGF and
      hypoxia both drive MDA-MB-468 cells to phenotypically similar mesenchymal states.
      Comparing the transcriptional response to EGF and hypoxia, we have identified
      differences in the cellular signalling pathways that mediate, and are influenced
      by, EMT. Significant differences were observed for a number of important cellular
      signalling components previously implicated in EMT, such as HBEGF and VEGFA. We
      have shown that EGF- and hypoxia-induced transitions respond differently to
      treatment with chemical inhibitors (presented individually and in combinations)
      in these breast cancer cells. Unexpectedly, MDA-MB-468 cells grown under hypoxic
      growth conditions became even more mesenchymal following exposure to certain
      kinase inhibitors that prevent growth-factor induced EMT, including the mTOR
      inhibitor everolimus and the AKT1/2/3 inhibitor AZD5363. CONCLUSIONS: While
      resulting in a common phenotype, EGF and hypoxia induced subtly different
      signalling systems in breast cancer cells. Our findings have important
      implications for the use of kinase inhibitor-based therapeutic interventions in
      breast cancers, where these heterogeneous signalling landscapes will influence
      the therapeutic response.

PMID- 25975822
TI  - Who should do endovascular repair of complex aortic aneurysms and how should they
      do them?
AB  - BACKGROUND: Cure of aneurysms which involve the aorta at the level of the
      visceral arteries and the thoracoabdominal segment remains a considerable
      surgical enterprise with a relatively high mortality and morbidity despite
      improvements of the surgical procedure and anesthetic technique. Fenestrated and
      branched endovascular stent grafts are currently available offering an attractive
      less invasive option especially for most frail patients. These grafts are
      relatively recent, technically more demanding to insert than the current stent
      graft for infrarenal aneurysm and besides, given the relative low frequency of
      the disease, they are much less used by practitioners. Thus, unconditional
      widespread of this sophisticated technique may not necessarily benefit patients.
      METHODS: We reviewed our experiences and articles regarding this concern, 1) who
      should perform this new technique and 2) in what kind of setting. CONCLUSION:
      Based on the combined complexities of 1) patients selection, 2) proper planning
      and manufacturing of the graft, 3) the need for outstanding imaging and operating
      facilities, 4) and the required endovascular skill of physicians involved in the
      procedure, we feel that only highly specialized centers should be allowed to
      perform this complex procedure.

PMID- 25975821
TI  - Microarray transcriptional profiling of Arctic Mesorhizobium strain N33 at low
      temperature provides insights into cold adaption strategies.
AB  - BACKGROUND: Arctic Mesorhizobium strain N33 was isolated from nodules of the
      legume Oxytropis arctobia in Canada's eastern Arctic. This symbiotic bacterium
      can grow at temperatures ranging from 0 to 30  degrees C, fix nitrogen at 10 
      degrees C, and is one of the best known cold-adapted rhizobia. Despite the
      economic potential of this bacterium for northern regions, the key molecular
      mechanisms of its cold adaptation remain poorly understood. RESULTS: Using a
      microarray printed with 5760 Arctic Mesorhizobium genomic clones, we performed a
      partial transcriptome analysis of strain N33 grown under eight different
      temperature conditions, including both sustained and transient cold treatments,
      compared with cells grown at room temperature. Cells treated under constant (4
      and 10  degrees C) low temperatures expressed a prominent number of induced genes
      distinct from cells treated to short-term cold-exposure (<60 min), but exhibited
      an intermediate expression profile when exposed to a prolonged cold exposure (240
      min). The most prominent up-regulated genes encode proteins involved in
      metabolite transport, transcription regulation, protein turnover, oxidoreductase
      activity, cryoprotection (mannitol, polyamines), fatty acid metabolism, and
      membrane fluidity. The main categories of genes affected in N33 during cold
      treatment are sugar transport and protein translocation, lipid biosynthesis, and
      NADH oxidoreductase (quinone) activity. Some genes were significantly down
      regulated and classified in secretion, energy production and conversion, amino
      acid transport, cell motility, cell envelope and outer membrane biogenesis
      functions. This might suggest growth cessation or reduction, which is an
      important strategy to adjust cellular function and save energy under cold stress
      conditions. CONCLUSION: Our analysis revealed a complex series of changes
      associated with cold exposure adaptation and constant growth at low temperatures.
      Moreover, it highlighted some of the strategies and different physiological
      states that Mesorhizobium strain N33 has developed to adapt to the cold
      environment of the Canadian high Arctic and has revealed candidate genes
      potentially involved in cold adaptation.

PMID- 25975823
TI  - Systematic review and mixed treatment comparison of intravitreal aflibercept with
      other therapies for diabetic macular edema (DME).
AB  - BACKGROUND: This was an indirect comparison of the effectiveness of intravitreal
      aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if
      different periods, after an initial monthly dosing period) (2q8) and other
      diabetic macular edema (DME) therapies at doses licensed outside the USA.
      METHODS: A comprehensive search was undertaken to source relevant studies.
      Feasibility networks were prepared to identify viable comparisons of 12-month
      outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were
      assessed for clinical and statistical homogeneity. Pooled effect sizes (mean
      difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed-
      and random-effects models. Indirect comparisons were performed using Bucher
      analysis. If at least one 'head-to-head' study was found then a mixed treatment
      comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons
      could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal
      ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus
      dexamethasone 0.7 mg implants (three studies). RESULTS: There was an increase in
      mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by
      4.67 letters [95% credible interval (CrI): 2.45-6.87] in the fixed-effect MTC
      model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52-7.11]
      in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the
      proportion of patients gaining >= 10 Early Treatment Diabetic Retinopathy Study
      letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95%
      CI: 1.29-3.40]) in the fixed-effect model. There were no significant differences
      in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg
      implants. CONCLUSIONS: Studies of IVT-AFL 2q8 showed improved 12-month visual
      acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg
      implants based on indirect comparisons. These analyses are subject to a number of
      limitations which are inherent in indirect data comparisons.

PMID- 25975824
TI  - Epigenetic dynamics during CD4(+) T cells lineage commitment.
AB  - T cell lymphopoiesis is a complex, stepwise process in which the transcriptional
      program of the progenitor cells is progressively adapted in order to generate
      mature phenotypes. This transcriptional program in differentiated cells is also
      very flexible, allowing the silencing or activation of critical genes in response
      to extrinsic or intrinsic stimuli, or, in the case of progenitors, to
      developmental signals. Thus, progenitor and mature cells must maintain a balance
      between stability, to preserve their phenotypic identity, and plasticity, to
      respond and adapt to stimuli. A long-standing question is, therefore, how the
      transcriptional program is regulated to allow both controlled differentiation and
      a flexible response. Here we review the contribution of epigenetic mechanisms to
      transcriptional control during CD4(+) T cell differentiation and the ways in
      which these mechanisms interact with key transcription factors to ensure proper
      maturation and maintenance of cell identity. This article is part of a Directed
      Issue entitled: Epigenetics dynamics in development and disease. 

PMID- 25975826
TI  - Leukocyte telomere length in patients with schizophrenia: A meta-analysis.
AB  - Schizophrenia has been suggested as a syndrome of accelerated aging. Telomere
      length (TL) decrease is considered one biological marker associated with age and
      can be accelerated by pathological characteristics present in schizophrenia.
      Several studies evaluated TL in schizophrenia, but the results are still
      controversial. The aim of this study was to conduct a meta-analysis of the
      existing results of TL in leukocytes of individuals with schizophrenia compared
      to healthy controls. A search was performed in PubMed, using the keywords
      'telomere schizophrenia' and 'telomere psychosis'. We included data from original
      articles that measured TL in leukocytes of human patients with schizophrenia and
      healthy control subjects. 45 articles were found, but only 7 met our criteria.
      Telomere length of controls was not statistically different from that of patients
      with schizophrenia (p=0.07). Crossvalidation with the leave-one-out method
      resulted in a significant model (p=0.03) in which TL of individuals with
      schizophrenia is smaller than control (SMD=0.38; 95% CI=[0.05, 0.72]). We also
      propose a biological pathway through which schizophrenia could promote telomere
      erosion and how antipsychotics might compensate this loss. There are few studies
      made on this subject with diverse methodology and heterogeneous sample. Some
      articles did not consider other possible influences on TL. Overall our results
      suggest that TL is decreased in schizophrenia. Although this is consistent with
      the idea of accelerated aging, schizophrenia is a complex disease and there are
      several factors that influence TL that should be controlled in future studies. 

PMID- 25975827
TI  - Longitudinal validation of psychosis risk screening tools.
AB  - The development of widely used interview tools has helped to standardize the
      criteria for a "clinical high risk" syndrome, thus enabling advances in efforts
      to develop interventions for this phase of illness. These assessments, however,
      are burdensome to administer and not likely to be adopted for widespread use.
      Scalable early intervention depends on the availability of brief, low-cost
      assessment tools that can serve to screen populations of interest or triage
      treatment-seekers toward specialized care. The current study examines the
      sensitivity, specificity, and predictive strength of three self-report measures
      (Prime Screen-Revised, Prodromal Questionnaire-Brief, and Youth Psychosis at Risk
      Questionnaire-Brief) with regard to psychosis onset and symptom persistence over
      six months of follow-up within an indicated sample of 54 adolescents and young
      adults ages 12-22. Within this sample, all three measures demonstrated excellent
      sensitivity to emerging psychosis and strong agreement with clinician evaluations
      of attenuated psychosis symptoms. Additionally, all screeners obtained negative
      predictive values of 1.00 with regard to psychosis onset, indicating that an
      individual scoring below the recommended threshold score would be extremely
      unlikely to develop psychosis over the following six months. The longitudinal
      validation of psychosis risk screening tools constitutes an important step toward
      establishing a standard of care for early identification and monitoring in this
      vulnerable population. 

PMID- 25975828
TI  - Integrative meta-analysis of differentially expressed genes in osteoarthritis
      using microarray technology.
AB  - The aim of the present study was to identify differentially expressed (DE) genes
      in patients with osteoarthritis (OA), and biological processes associated with
      changes in gene expression that occur in this disease. Using the INMEX
      (integrative meta-analysis of expression data) software tool, a meta-analysis of
      publicly available microarray Gene Expression Omnibus (GEO) datasets of OA was
      performed. Gene ontology (GO) enrichment analysis was performed in order to
      detect enriched functional attributes based on gene-associated GO terms. Three
      GEO datasets, containing 137 patients with OA and 52 healthy controls, were
      included in the meta-analysis. The analysis identified 85 genes that were
      consistently differentially expressed in OA (30 genes were upregulated and 55
      genes were downregulated). The upregulated gene with the lowest P-value (P=5.36E
      07) was S-phase kinase-associated protein 2, E3 ubiquitin protein ligase (SKP2).
      The downregulated gene with the lowest P-value (P=4.42E-09) was Proline rich 5
      like (PRR5L). Among the 210 GO terms that were associated with the set of DE
      genes, the most significant two enrichments were observed in the GO categories of
      'Immune response', with a P-value of 0.000129438, and 'Immune effectors process',
      with a P-value of 0.000288619. The current meta-analysis identified genes that
      were consistently DE in OA, in addition to biological pathways associated with
      changes in gene expression that occur during OA, which may provide insight into
      the molecular mechanisms underlying the pathogenesis of this disease.

PMID- 25975829
TI  - Clean carbon nanotubes coupled to superconducting impedance-matching circuits.
AB  - Coupling carbon nanotube devices to microwave circuits offers a significant
      increase in bandwidth (BW) and signal-to-noise ratio. These facilitate fast non
      invasive readouts important for quantum information processing, shot noise and
      correlation measurements. However, creation of a device that unites a low
      disorder nanotube with a low-loss microwave resonator has so far remained a
      challenge, due to fabrication incompatibility of one with the other. Employing a
      mechanical transfer method, we successfully couple a nanotube to a gigahertz
      superconducting matching circuit and thereby retain pristine transport
      characteristics such as the control over formation of, and coupling strengths
      between, the quantum dots. Resonance response to changes in conductance and
      susceptance further enables quantitative parameter extraction. The achieved near
      matching is a step forward promising high-BW noise correlation measurements on
      high impedance devices such as quantum dot circuits. 

PMID- 25975825
TI  - Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities
      of osteoarthritic chondrocytes.
AB  - The development of disease-modifying pharmacologic therapy for osteoarthritis
      currently faces major obstacles largely because the pathogenetic mechanisms for
      the development of osteoarthritis remain unclear. Previous studies suggest that
      the alterations in expression of catabolic and anabolic genes in articular
      chondrocytes may be involved in the pathogenesis of osteoarthritis. However, the
      regulatory mechanisms for gene expression in osteoarthritic chondrocytes are
      largely unknown. The objective of this review is to highlight the recent studies
      on epigenetic regulation of gene expression in the development of osteoarthritis.
      The review will begin with current understanding of epigenetic mechanisms,
      especially the newly emerging areas including the regulatory role of non-coding
      RNAs in gene expression and crosstalk among the epigenetic mechanisms. The main
      content of this review focuses on the significance of epigenetic regulation of
      the expression of catabolic and anabolic genes in osteoarthritic chondrocytes,
      including the regulatory roles of various epigenetic mechanisms in the expression
      of genes for specific matrix-degrading proteinases, cytokines, and extracellular
      matrix proteins. Recent novel findings on the epigenetic regulation of specific
      transcription factor genes are particularly important for the understanding of
      osteoarthritis pathogenesis, as these transcription factors may act as upstream
      regulators of multiple catabolic and anabolic genes. In conclusion, these recent
      advances in epigenetic studies have shed light on the importance of epigenetic
      regulation of gene expression in the development of osteoarthritis, leading to a
      better understanding of the epigenetic mechanisms underlying the pathogenesis of
      osteoarthritis. This may promote the development of new epigenetics-based
      strategies for the treatment of osteoarthritis. This article is part of a
      Directed Issue entitled: Epigenetics dynamics in development and disease. 

PMID- 25975830
TI  - The first antenatal appointment: An exploratory study of the experiences of women
      with a diagnosis of mental illness.
AB  - OBJECTIVE: to explore and gain insight into the expectations and experiences of
      women with a pre-existing diagnosis of mental illness, of their first booking
      appointment; to make recommendations for practice development and collaborative
      partnership working between healthcare professionals. DESIGN: a qualitative
      design using semi structured interviews and thematic analysis of the data. QSR
      NVivo 10 software is used to organise the data into themes. SETTING: the
      interviews took place either at the women's homes, or within the antenatal
      service with the consent of the woman and relevant practitioners. PARTICIPANTS:
      twelve participants were selected from one antenatal clinic and one perinatal
      mental health service. FINDINGS: the themes identified within the data included
      the lack of information prior to the initial midwife booking appointment; the
      perception of too much information at the initial booking appointment and women
      not being clear about their mental health needs at this time; a general
      positivity about disclosing mental illness diagnoses; overall positive thoughts
      about midwives although some midwives appeared less knowledgeable about bipolar
      disorder, and perceptions about a lack of joined up working between antenatal and
      perinatal mental health services. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      it is recommended that GPs receive adequate training in order to equip them with
      the skills needed to discuss sensitive issues around perinatal mental illness and
      the impact on pregnancy and childbirth. Women require more information about
      their booking appointment, and it would be beneficial for their emotional and
      physical health needs to be assessed at each follow-up antenatal appointment.
      Midwives need to be facilitated to receive up-to-date knowledge of antenatal and
      postnatal mental illness and treatments, and the referral process to perinatal
      mental health services.

PMID- 25975831
TI  - Increasing the density of nanomedicines improves their ultrasound-mediated
      delivery to tumours.
AB  - Nanomedicines have provided fresh impetus in the fight against cancer due to
      their selectivity and power. However, these agents are limited when delivered
      intravenously due to their rapid clearance from the bloodstream and poor passage
      from the bloodstream into target tumours. Here we describe a novel stealthing
      strategy which addresses both these limitations and thereby demonstrate that both
      the passive and mechanically-mediated tumour accumulation of the model
      nanomedicine adenovirus (Ad) can be substantially enhanced. In our strategy gold
      nanoparticles were thoroughly modified with 2kDa polyethyleneglycol (PEG) and
      then linked to Ad via a single reduction-cleavable 5kDa PEG. The resulting Ad
      gold-PEG construct was compared to non-modified Ad or conventionally stealthed Ad
      poly[N-(2-hydroxypropyl)methacrylamide] (Ad-PHPMA). Notably, although Ad-gold-PEG
      was of similar size and surface charge to Ad-PHPMA the increase in density,
      resulting from the inclusion of the gold nanoparticles, provided a substantial
      enhancement of ultrasound-mediated transport. In an in vitro tumour mimicking
      phantom, the level and distance of Ad-gold-PEG transport was shown to be
      substantially greater than achieved with Ad-PHPMA. In in vivo studies 0.1% of an
      unmodified Ad dose was shown to accumulate in tumours, whereas over 12% of the
      injected dose was recovered from the tumours of mice treated with Ad-gold-PEG and
      ultrasound. Ultimately, a significant increase in anti-tumour efficacy resulted
      from this strategy. This stealthing and density-increasing technology could
      ultimately enhance clinical utility of intravenously delivered nanoscale
      medicines including viruses, liposomes and antibodies. 

PMID- 25975832
TI  - Effects of emergency cervical cerclage on pregnancy outcome: a retrospective
      study of 158 cases.
AB  - The aim of this study was to evaluate the effectiveness and safety of emergency
      cervical cerclage in women with advanced cervical dilatation and bulging of fetal
      membranes. The study included 158 women who underwent emergency cervical cerclage
      because of cervix dilatation and protruding membranes in mid-trimester at Sun Yat
      sen Memorial Hospital of Sun Yat-sen University. Pregnancy outcomes and pregnancy
      outcome related to clinical features were analyzed retrospectively. Analysis
      revealed that the placement of emergency cerclage led to the delivery of live
      infants with a success rate of 82.28%. The mean interval between cerclage and
      delivery was 52.16.+/-26.62 days, with a mean gestation at delivery of 30.3+/-4.7
      weeks and a mean birth weight of 1934.69+/-570.37 g. No severe maternal
      complications such as maternal death, hematosepsis, and hysterorrhexis occurred
      after the operation. Two women (1.25%) had laceration of the cervix, 1 woman
      (0.61%) suffered pulmonary edema, and 2 women (1.25%) developed deep vein
      thrombosis (DVT). There were significant correlations between the pregnancy
      outcome and risk factors, including any presenting symptoms, cervical dilatation,
      postoperative white blood cell count, and C-reactive protein (CRP) value. No
      significant difference was found in women with good vs. poor outcome in terms of
      maternal age and obstetric histories. Emergency cervical cerclage is effective in
      prolonging pregnancy and improving neonatal outcome in women with cervical
      incompetence. It should be considered a viable option for women with a dilated
      cervix in mid-trimester. 

PMID- 25975833
TI  - Identification of Sex-Linked SNPs and Sex-Determining Regions in the Yellowtail
      Genome.
AB  - Unlike the conservation of sex-determining (SD) modes seen in most mammals and
      birds, teleost fishes exhibit a wide variety of SD systems and genes. Hence, the
      study of SD genes and sex chromosome turnover in fish is one of the most
      interesting topics in evolutionary biology. To increase resolution of the SD gene
      evolutionary trajectory in fish, identification of the SD gene in more fish
      species is necessary. In this study, we focused on the yellowtail, a species
      widely cultivated in Japan. It is a member of family Carangidae in which no
      heteromorphic sex chromosome has been observed, and no SD gene has been
      identified to date. By performing linkage analysis and BAC walking, we identified
      a genomic region and SNPs with complete linkage to yellowtail sex. Comparative
      genome analysis revealed the yellowtail SD region ancestral chromosome structure
      as medaka-fugu. Two inversions occurred in the yellowtail linage after it
      diverged from the yellowtail-medaka ancestor. An association study using wild
      yellowtails and the SNPs developed from BAC ends identified two SNPs that can
      reasonably distinguish the sexes. Therefore, these will be useful genetic markers
      for yellowtail breeding. Based on a comparative study, it was suggested that a
      PDZ domain containing the GIPC protein might be involved in yellowtail sex
      determination. The homomorphic sex chromosomes widely observed in the Carangidae
      suggest that this family could be a suitable marine fish model to investigate the
      early stages of sex chromosome evolution, for which our results provide a good
      starting point. 

PMID- 25975834
TI  - Variation in Adult Plant Phenotypes and Partitioning among Seed and Stem-Borne
      Roots across Brachypodium distachyon Accessions to Exploit in Breeding Cereals
      for Well-Watered and Drought Environments.
AB  - Seedling roots enable plant establishment. Their small phenotypes are measured
      routinely. Adult root systems are relevant to yield and efficiency, but
      phenotyping is challenging. Root length exceeds the volume of most pots. Field
      studies measure partial adult root systems through coring or use seedling roots
      as adult surrogates. Here, we phenotyped 79 diverse lines of the small grass
      model Brachypodium distachyon to adults in 50-cm-long tubes of soil with
      irrigation; a subset of 16 lines was droughted. Variation was large (total
      biomass, *8; total root length [TRL], *10; and root mass ratio, *6), repeatable,
      and attributable to genetic factors (heritabilities ranged from approximately 50%
      for root growth to 82% for partitioning phenotypes). Lines were dissected into
      seed-borne tissues (stem and primary seminal axile roots) and stem-borne tissues
      (tillers and coleoptile and leaf node axile roots) plus branch roots. All lines
      developed one seminal root that varied, with branch roots, from 31% to 90% of TRL
      in the well-watered condition. With drought, 100% of TRL was seminal, regardless
      of line because nodal roots were almost always inhibited in drying topsoil.
      Irrigation stimulated nodal roots depending on genotype. Shoot size and tillers
      correlated positively with roots with irrigation, but partitioning depended on
      genotype and was plastic with drought. Adult root systems of B. distachyon have
      genetic variation to exploit to increase cereal yields through genes associated
      with partitioning among roots and their responsiveness to irrigation. Whole-plant
      phenotypes could enhance gain for droughted environments because root and shoot
      traits are coselected. 

PMID- 25975836
TI  - Quantitative microfluidic fluorescence microscopy to study vaso-occlusion in
      sickle cell disease.

PMID- 25975835
TI  - Knocking Down of Isoprene Emission Modifies the Lipid Matrix of Thylakoid
      Membranes and Influences the Chloroplast Ultrastructure in Poplar.
AB  - Isoprene is a small lipophilic molecule with important functions in plant
      protection against abiotic stresses. Here, we studied the lipid composition of
      thylakoid membranes and chloroplast ultrastructure in isoprene-emitting (IE) and
      nonisoprene-emitting (NE) poplar (Populus * canescens). We demonstrated that the
      total amount of monogalactosyldiacylglycerols, digalactosyldiacylglycerols,
      phospholipids, and fatty acids is reduced in chloroplasts when isoprene
      biosynthesis is blocked. A significantly lower amount of unsaturated fatty acids,
      particularly linolenic acid in NE chloroplasts, was associated with the reduced
      fluidity of thylakoid membranes, which in turn negatively affects photosystem II
      photochemical efficiency. The low photosystem II photochemical efficiency in NE
      plants was negatively correlated with nonphotochemical quenching and the energy
      dependent component of nonphotochemical quenching. Transmission electron
      microscopy revealed alterations in the chloroplast ultrastructure in NE compared
      with IE plants. NE chloroplasts were more rounded and contained fewer grana
      stacks and longer stroma thylakoids, more plastoglobules, and larger associative
      zones between chloroplasts and mitochondria. These results strongly support the
      idea that in IE species, the function of this molecule is closely associated with
      the structural organization and functioning of plastidic membranes. 

PMID- 25975837
TI  - ALK-negative anaplastic large cell lymphoma is sensitive to bortezomib through
      Noxa upregulation and release of Bax from Bcl-2.

PMID- 25975838
TI  - Proteasome inhibitors block Ikaros degradation by lenalidomide in multiple
      myeloma.

PMID- 25975839
TI  - Characterization of CMV-specific CD4+ T-cell reconstitution following stem cell
      transplantation through the use of HLA Class II-peptide tetramers identifies
      patients at high risk of recurrent CMV reactivation.

PMID- 25975840
TI  - Mice are poor heme absorbers and do not require intestinal Hmox1 for dietary heme
      iron assimilation.

PMID- 25975842
TI  - Do not turn a blind eye to alkyl nitrite (poppers)!

PMID- 25975841
TI  - Apolipoprotein E deficiency and high-fat diet cooperate to trigger lipidosis and
      inflammation in the lung via the toll-like receptor 4 pathway.
AB  - Apolipoprotein E deficiency (ApoE(-/-)) combined with a high-fat Western-type
      diet (WD) is known to activate the toll-like receptor (TLR4) pathway and promote
      atherosclerosis. However, to date, the pathogenic effects of these conditions on
      the lung have not been extensively studied. Therefore, the present study examined
      the effects of ApoE(-/-) and a WD on lung injury and investigated the underlying
      mechanisms. ApoE(-/-) and wild-type mice were fed a WD or normal chow diet for 4,
      12 and 24 weeks. Lung inflammation, lung cholesterol content and cytokines
      profiles in broncho-alveolar lavage fluid (BALF) were determined. TLR4 and its
      main downstream molecules were analyzed with western blot analysis. In addition,
      the role of the TLR4 pathway was further validated using TLR4-targeted gene
      silencing. The results showed that ApoE(-/-) mice developed lung lipidosis
      following 12 weeks of receiving a WD, as evidenced by an increased lung
      cholesterol content. Moreover, dependent on the time period of receiving the
      diet, those mice exhibited pulmonary inflammation, which was manifested by
      initial leukocyte recruitment (at 4 weeks), by increased alveolar septal
      thickness and mean linear intercept as well as elevated production of
      inflammation mediators (at 12 weeks), and by granuloma formation (at 24 weeks).
      The expression levels of TLR4, myeloid differentiation primary response 88
      (MyD88) and nuclear factor kappa B were markedly upregulated in ApoE(-/-) WD mice
      at week 12. However, these effects were ameliorated by shRNA-mediated knockdown
      of TLR4. By contrast, ApoE(-/-) ND or wild-type WD mice exhibited low-grade or no
      inflammation and mild lipidosis. The levels of TLR4 and MyD88 in those mice
      showed only minor changes. In conclusion, ApoE deficiency acts synergistically
      with a WD to trigger lung lipidosis and inflammation at least in part via TLR4
      signaling.

PMID- 25975843
TI  - Are the proposed benefits of melatonin-rich foods too hard to swallow?
AB  - Melatonin has been proposed as a potent anti-oxidant, and its presence in many
      plants and foods has been suggested to be beneficial for health. Indeed, the
      concentrations of melatonin in blood and the melatonin metabolite 6
      sulphatoxymelatonin in urine have been found to increase significantly after
      ingestion of melatonin-rich foods. In this review, the studies have been
      critically evaluated in light of the reported plant melatonin concentrations and
      our knowledge of pharmacokinetics of orally administered pure melatonin. In the
      case of studies involving measurement of plasma melatonin following ingestion of
      beer or fruits, the reported increase in melatonin is not consistent with the
      amount of melatonin ingested. Similarly, the amount of melatonin metabolite
      excreted following ingestion of melatonin-rich foods greatly exceeded the amount
      of melatonin ingested. It is concluded that studies reporting the appearance of
      melatonin in blood and its metabolites in urine following ingestion of melatonin
      rich foods are flawed. While there may be health benefits for certain foods, it
      is difficult to accept that these are due to their low melatonin content.

PMID- 25975844
TI  - Predominant role of the hypothalamic-pituitary axis, not the ovary, in different
      types of abnormal cycle induction by postnatal exposure to high dose p-tert
      octylphenol in rats.
AB  - To determine whether it is the hypothalamic-pituitary axis or the ovary that
      plays the predominant role in abnormal estrous cycling induction by postnatal
      exposure to estrogenic compounds, female rats were subcutaneously injected with
      100mg/kg p-tert-octylphenol or vehicle for 5 or 15 days after birth (OP-PND5, OP
      PND15 or control). Ovaries were exchanged between control and treated groups on
      PND28. Controls receiving control or OP-PND5 ovaries showed normal cycles within
      4 weeks after the exchange, and corpora lutea were detected in transplanted
      ovaries. Controls receiving OP-PND15 ovaries consistently increased persistent
      estrus (PE). OP-PND15 rats receiving control or OP-PND15 ovaries immediately
      descended into PE, and transplanted ovaries were atrophic with cystic follicles,
      indicating anovulation. OP-PND5 rats receiving control or OP-PND5 ovaries showed
      early onset of PE after normal cycling. The hypothalamic-pituitary axis is
      predominant in abnormal cycling induction by postnatal exposure to OP. OP-PND15
      ovaries were impaired compared to other groups. 

PMID- 25975845
TI  - Molecular diagnosis of egg allergy: an update.
AB  - Hen's egg allergy affects up to 2.5% of young children and is potentially life
      threatening. Several phenotypes of egg allergy have been identified, including
      those who tolerate extensively heated egg in bakery products. Diagnosis and
      monitoring for resolution often requires oral food challenges, which can result
      in anaphylaxis. Newer approaches, such as component-resolved diagnostics,
      microarray analysis and epitope mapping, are being evaluated to determine if
      these strategies can replace or reduce the need for oral food challenges. Studies
      suggest that elevated levels of ovomucoid IgE indicate an inability to tolerate
      extensively heated forms of egg. Egg protein-specific IgE/IgG4 ratios may be
      helpful in predicting tolerance. Additionally, patients with conformational
      epitopes to hen's egg are more likely to resolve their allergy compared with
      those with IgE binding to sequential epitopes. The pairing of microarray
      technology to epitope mapping is a potential tool to improve diagnosis. This
      review examines the current body of literature on these tools. 

PMID- 25975846
TI  - Reunifying abused or neglected children: Decision-making and outcomes.
AB  - Little is known about decision-making regarding the reunification of children in
      care, or about the consequences of these decisions for the children concerned.
      This study compared decision-making and outcomes for 149 maltreated children in
      seven English authorities (68 reunified, 81 who remained in care). Children were
      followed up six months after their return home or, for those who were not
      reunified, six months after the 'effective decision' that they should remain in
      care. They were followed up again four years (on average) after the return or
      effective decision. Data were extracted from case files at baseline and six month
      follow-up and were gathered from surveys of social workers and teachers at final
      follow-up. The two key predictors of reunification were assessments that parental
      problems had improved and that risks to the child were not unacceptably high. Two
      thirds returned to improved family circumstances, sometimes due to a change in
      the household they returned to, but others were reunified despite persisting
      concerns. However 35% re-entered care within six months and 63% re-entered at
      some point during the four-year follow-up period, often due to recurring abuse or
      neglect. At final follow-up remaining in care was the strongest predictor of
      positive outcomes on a range of dimensions, even once children's characteristics
      and histories were taken into account. Outcomes were especially poor for
      neglected children who were reunified, irrespective of whether reunification was
      stable or unstable. Results show the potential of the care system to produce
      positive outcomes for maltreated children. 

PMID- 25975848
TI  - Stereotactic body radiotherapy for centrally located early-stage non-small cell
      lung cancer or lung metastases from the RSSearch((r)) patient registry.
AB  - BACKGROUND: The purpose of this study was to evaluate treatment patterns and
      outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary
      non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch((r))
      Patient Registry, an international, multi-center patient registry dedicated to
      radiosurgery and SBRT. METHODS: Eligible patients included those with centrally
      located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or
      lung metastases treated with SBRT between November 2004 and January 2014.
      Descriptive analysis was used to report patient demographics and treatment
      patterns. Overall survival (OS) and local control (LC) were determined using
      Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria
      for Adverse Events version 3.0. RESULTS: In total, 111 patients with 114
      centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were
      treated with SBRT at 19 academic and community-based radiotherapy centers in the
      US and Germany. Median follow-up was 17 months (range, 1-72). Median age was 74
      years for primary NSCLC patients and 65 years for lung metastases patients (p <
      0.001). SBRT dose varied from 16 - 60 Gy (median 48 Gy) delivered in 1-5
      fractions (median 4 fractions). Median dose to centrally located primary NSCLC
      was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED10
      was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two
      year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009)
      and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for
      primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3
      or higher acute or late toxicities. CONCLUSION: Overall, patients with centrally
      located primary NSCLC were older and received higher doses of SBRT than those
      with lung metastases. Despite these differences, LC and OS was favorable for
      patients with central lung tumors treated with SBRT. Reported toxicity was low,
      although low grade toxicities were observed in patients where dose tolerances
      approached or exceeded published guidelines. Prospective studies are needed to
      further define the optimal SBRT dose for this cohort of patients. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier: NCT01885299.

PMID- 25975849
TI  - Intention of nurses to receiving influenza vaccination before the 2013-14 season.
AB  - A study was conducted to determine the influenza vaccination uptake rate of
      nurses in Hong Kong after the pH1N1 epidemic, and examine their intention for
      vaccination before the next influenza season. Questionnaires in Chinese with
      multiple choice responses were delivered by post through 4 nurses organizations.
      The following were explored: intentions and reasons for vaccination in the
      forthcoming season; perceptions of influenza outbreak risk; attitudes toward
      professional obligation and vaccination policies. Cramer's V and Eta values were
      calculated to analyze association and effect size. Between March and May 2013,
      analysis was made on 1,934 (6.8%) valid questionnaires, with 620 (30.7%) having
      received influenza vaccination before the season of 2012-13. Some 30.7% and 42%
      intended to accept and decline vaccination respectively in the forthcoming season
      (2013-14) while 27.3% remained indecisive. Over 80% of indecisive nurses had
      refused vaccination in the last season. More nurses refusing (18.1%) or
      indecisive (9.8%) of vaccination perceived being "significantly unwell" after
      past vaccinations, compared to only 1% in those who intended to accept. Expert
      opinions and guidelines were important for making decision on vaccination in 40%
      of nurses. The ranking of professional responsibilities of vaccination in
      indecisive nurses was between those declining and accepting future vaccination.
      Overall, past vaccination experience, professional responsibilities and reference
      to guidelines were major factors affecting nurses' decision on future vaccination
      against influenza in Hong Kong. The results might however not be generalizable to
      all nurses as the analyses were restricted to those responding to the appeal from
      selected professional organisations. 

PMID- 25975847
TI  - Basic MR relaxation mechanisms and contrast agent design.
AB  - The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone
      continuous and substantial evolution by virtue of hardware and software
      innovations and the development and implementation of exogenous contrast media.
      Thirty years since the first MRI contrast agent was approved for clinical use, a
      reliance on MR contrast media persists, largely to improve image quality with
      higher contrast resolution and to provide additional functional characterization
      of normal and abnormal tissues. Further development of MR contrast media is an
      important component in the quest for continued augmentation of diagnostic
      capabilities. In this review we detail the many important considerations when
      pursuing the design and use of MR contrast media. We offer a perspective on the
      importance of chemical stability, particularly kinetic stability, and how this
      influences one's thinking about the safety of metal-ligand-based contrast agents.
      We discuss the mechanisms involved in MR relaxation in the context of probe
      design strategies. A brief description of currently available contrast agents is
      accompanied by an in-depth discussion that highlights promising MRI contrast
      agents in the development of future clinical and research applications. Our
      intention is to give a diverse audience an improved understanding of the factors
      involved in developing new types of safe and highly efficient MR contrast agents
      and, at the same time, provide an appreciation of the insights into physiology
      and disease that newer types of responsive agents can provide.

PMID- 25975850
TI  - Pili of Mycobacterium tuberculosis: current knowledge and future prospects.
AB  - Many pathogenic bacteria express filamentous appendages, termed pili, on their
      surface. These organelles function in several important bacterial processes,
      including mediating bacterial interaction with, and colonization of the host,
      signalling events, locomotion, DNA uptake, electric conductance, and biofilm
      formation. In the last decade, it has been established that the tuberculosis
      causing bacterium, Mycobacterium tuberculosis, produces two pili types: curli and
      type IV pili. In this paper, we review studies on M. tuberculosis pili,
      highlighting their structure and biological significance to M. tuberculosis
      pathogenesis, and discuss their potential as targets for therapeutic intervention
      and diagnostic test development. 

PMID- 25975851
TI  - Phenotypic screening of a library of compounds against metastatic and non
      metastatic clones of a canine mammary gland tumour cell line.
AB  - Metastases are associated with a poor prognosis for canine mammary gland tumours
      (CMGTs). Metastatic and non-metastatic clones were isolated previously from a
      single malignant CMGT cell line. The difference in metastatic potential between
      the two cell lines was hypothesised to be associated with distinct cellular
      signalling. The aim of this study was to screen for compounds that specifically
      target metastatic cells in order to improve CMGT therapeutic outcomes. The two
      clonal cell lines were characterised by transcriptome analysis and their
      sensitivity to a library of 291 different compounds was compared. The metastatic
      clone exhibited elevated expression of molecules associated with degradation of
      the extracellular matrix, epithelial-mesenchymal transition and cancer stem cell
      phenotype. This was confirmed using a matrigel invasion assay and by assessment
      of aldehyde dehydrogenase activity. The mitochondrial respiratory chain complex
      inhibitors (MRCIs; rotenone, antimycin and oligomycin) significantly inhibited
      the growth of the metastatic clone. Although MRCIs similarly depleted
      mitochondrial ATP in both clones, the subsequent cellular response was different,
      with toxicity to the metastatic clone being independent of AMP-activated protein
      kinase activity. The results of this study suggest a potential utility of MRCIs
      as anti-tumour agents against metastatic CMGTs. Further studies are needed to
      investigate the clinical utility of MRCIs and to determine the association
      between MRCI sensitivity and malignancy. 

PMID- 25975852
TI  - Lack of interference with diagnostic testing for tuberculosis in goats
      experimentally exposed to Corynebacterium pseudotuberculosis.
AB  - It has been suggested that infection with Corynebacterium pseudotuberculosis, the
      pathogen responsible for caseous lymphadenitis (CLA), might interfere with
      diagnostic testing for tuberculosis (TB), due to antigenic similarities between
      this particular type of bacterium and those expressed by mycobacteria. The aim of
      the present study was to investigate whether experimental infection with C.
      pseudotuberculosis in goats impacted on TB testing, using single and comparative
      intradermal tuberculin (SIT and SCIT respectively) tests and interferon (IFN)
      gamma assay. No positive reactors were detected among the CLA-affected goats
      using the SIT/SCIT tests or the interferon IFN-gamma assay. A proportion of goats
      showed inconclusive results to the SIT test and reactions to Mycobacterium avium.
      There was no evidence that infection with C. pseudotuberculosis interferes with
      diagnostic testing for TB using standard interpretation of the SIT, SCIT and IFN
      gamma tests. 

PMID- 25975853
TI  - Immunological barriers: Functional histology of the spleen.

PMID- 25975854
TI  - Direct coating of culture medium from cells secreting classical swine fever virus
      E2 antigen on ELISA plates for detection of E2-specific antibodies.
AB  - The envelope glycoprotein E2 of classical swine fever virus (CSFV) is widely used
      as a marker for measuring vaccine efficacy and antibody titer. The glycosylation
      profile of E2 may affect the immunogenicity of the vaccine and the timing of re
      vaccination. In this study, a human embryonic kidney cell line was used to
      secrete fully-glycosylated CSFV E2, which was then coated onto ELISA plates
      without purification or adjustment. The resulting E2-secreting medium-direct
      coating (E2-mDc) ELISA was successfully used to measure anti-E2 antibody titers
      in vaccinated and field pig sera samples. Compared with a virus neutralization
      test (as standard), the E2-mDc ELISA was found to be more accurate (90%) than a
      commercial CSFV antibody diagnostic kit (62%). In conclusion, the mammalian cell
      secreted antigen can provide cheap, accurate and effective assays for vaccine
      efficacy and disease diagnoses. 

PMID- 25975855
TI  - Characterization and comparison of the bacterial microbiota in different
      gastrointestinal tract compartments in horses.
AB  - The advance of new sequencing technologies has allowed more comprehensive
      characterization of complex microbial communities, including the ones inhabiting
      the intestinal tract. The presence of extreme environmental filters, such as low
      pH, digestive enzymes and anaerobic conditions along the tract, acts on the
      selection of unique bacteria in each compartment. The intestinal microbiota has
      an enormous impact on the maintenance of health. However, data about the bacteria
      present in the different intestinal compartments of horses are sparse. In this
      study, high throughput sequencing was used to characterize and compare bacterial
      profiles from different intestinal compartments of 11 horses scheduled for
      euthanasia for reasons other than gastrointestinal problems. Marked differences
      among compartments even at high taxonomic levels were found, with Firmicutes
      comprising the main bacterial phylum in all compartments. Lactobacillus spp. and
      Sarcina spp. predominated in the stomach and a marked increase of Streptococcus
      spp. occurred in the duodenum. Actinobacillus and Clostridium sensu stricto were
      the most abundant genera in the ileum and '5 genus incertae sedis', a genus from
      the Subdivision 5 class of the Verrucomicrobia, was the most abundant from the
      large colon through feces. There was a significant increase in diversity towards
      the distal gut with similar profiles observed from the cecum through feces at the
      class level. The bacterial population comprising the equine intestinal tract
      varies greatly among compartments and fecal samples may be useful as
      representative of changes occurring in the distal compartments. 

PMID- 25975856
TI  - Solvent Removal Induces a Reversible beta-to-alpha Switch in Oligomeric Abeta
      Peptide.
AB  - Solvation and hydration are key factors for determining the stability and folding
      of proteins, as well as the formation of amyloid fibrils and related polypeptide
      aggregates. Using attenuated total reflectance Fourier-transform infrared and
      solid-state NMR spectroscopy, we find that the Abeta peptide experiences a
      remarkable conformational switch from beta to alpha secondary structure upon
      solvent removal by lyophilization of oligomers. This transition is, contrary to
      Abeta fibrils, independent of concentration of organic co-solvents or co-solutes
      and is reversible upon re-addition of the solvent. Our data illuminate a
      previously unnoted secondary structural plasticity of the Abeta peptide in
      amyloid oligomers that could bear relevance for Abeta's interactions with
      cellular structures of low polarity. 

PMID- 25975857
TI  - Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond.
AB  - BACKGROUND: Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate
      (NMDA) receptor encephalitis are sparse. OBJECTIVE: To report the autoimmune
      psychiatric spectrum currently recognized in Mayo Clinic practice. METHODS:
      Medical record review, testing of stored serum and cerebrospinal fluid for IgGs
      reactive with synaptic receptors and ion channels, neuronal nuclear and
      cytoplasmic antigens (including glutamic acid decarboxylase 65-kDa isoform) and
      case-control comparison were conducted. Patients were categorized into group 1,
      all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n =
      213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n =
      13); healthy control subjects were also included (n = 173). RESULTS: In group 1,
      at least 1 serum autoantibody (but not NMDA receptor IgG) was detected in 36 of
      213 psychiatric inpatients. In total, 12 patients were determined retrospectively
      to have high-likelihood autoimmune encephalitic diagnoses. The most commonly
      detected autoantibody specificities were voltage-gated potassium channel ([Kv1]
      VGKC) complex (6) and calcium channel (P/Q type or N type; 5). Symptoms seen were
      as follows: depressive (8), anxious (7), psychotic (7), disorganized (5),
      suicidal (3), manic (1) and catatonic (1). In group 2, among 13 NMDA receptor IgG
      positive patients, 12 had encephalitis; their psychiatric symptoms were as
      follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic
      (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12
      NMDA receptor IgG-positive patients than in the 12 group 1 patients with high
      likelihood of encephalitis (p = 0.002). Antibody positivities were usually low
      positive in value among healthy controls (12 of 16 vs 3 of 12 group 1
      encephalitis cases, p = 0.025). NMDA receptor IgG was not detected in any healthy
      control subject. CONCLUSIONS: A spectrum of psychiatric autoimmunity beyond NMDA
      R IgG may be under-recognized. Diagnosis is facilitated by combining results of
      comprehensive psychiatric, laboratory, radiologic, and electrophysiologic
      evaluations.

PMID- 25975858
TI  - The live donor assessment tool: a psychosocial assessment tool for live organ
      donors.
AB  - BACKGROUND: Psychosocial evaluation is an important part of the live organ donor
      evaluation process, yet it is not standardized across institutions, and although
      tools exist for the psychosocial evaluation of organ recipients, none exist to
      assess donors. OBJECTIVE: We set out to develop a semistructured psychosocial
      evaluation tool (the Live Donor Assessment Tool, LDAT) to assess potential live
      organ donors and to conduct preliminary analyses of the tool's reliability and
      validity. METHODS: Review of the literature on the psychosocial variables
      associated with treatment adherence, quality of life, live organ donation
      outcome, and resilience, as well as review of the procedures for psychosocial
      evaluation at our center and other centers around the country, identified 9
      domains to address; these domains were distilled into several items each, in
      collaboration with colleagues at transplant centers across the country, for a
      total of 29 items. Four raters were trained to use the LDAT, and they
      retrospectively scored 99 psychosocial evaluations conducted on live organ donor
      candidates. Reliability of the LDAT was assessed by calculating the internal
      consistency of the items in the scale and interrater reliability between raters;
      validity was estimated by comparing LDAT scores between those with a "positive"
      evaluation outcome and "negative" outcome. RESULTS: The LDAT was found to have
      good internal consistency, inter-rater reliability, and showed signs of validity:
      LDAT scores differentiated the positive vs. negative outcome groups. CONCLUSIONS:
      The LDAT demonstrated good reliability and validity, but future research on the
      LDAT and the ability to implement the LDAT prospectively is warranted.

PMID- 25975859
TI  - Parameters of consultee satisfaction with inpatient academic psychiatric
      consultation services: a multicenter study.
AB  - BACKGROUND: Consultation-liaison psychiatrists commonly perceive consultee
      satisfaction as a useful global measure of consultation-liaison service
      performance. No tool exists to measure consultee satisfaction. A single-site
      study at Columbia University Medical Center elicited ratings of parameters
      importantly contributing to consultee satisfaction within consultation-liaison
      services. OBJECTIVE: The purpose of this study was to assess the generalizability
      of the rating of importance of these parameters in a larger, multicenter sample.
      METHODS: From October 2013 to January 2014, a confidential and voluntary Web
      based survey was distributed to 133 physicians at 7 academic centers in the
      United States asking them to rate the importance of 16 performance parameters
      (identified in the previous single-site study) in determining consultee
      satisfaction. RESULTS: Overall, 87 recipients (65%) responded to the survey.
      Among all the 16 items, there was no significant difference between sites in
      ratings of item importance. Of the 16 parameters, 9 received a mean rating in the
      "important" to "very important" range. Three items, "completion of consultation
      within 24 hours of request," "understanding the core questions being asked," and
      "practical and helpful management suggestions for medical staff" were rated as
      the most important. Quickly managing behavioral problems, management suggestions
      for nursing staff, verbal communication of recommendations, providing diagnostic
      clarification, facilitating transfer to inpatient psychiatry, and providing
      follow-up consultation were other parameters that were highly valued by
      consultees. CONCLUSIONS: We found good generalizability across academic medical
      centers for ratings of parameters important for consultee satisfaction with
      consultation-liaison services, which can provide the basis for a consultee
      satisfaction measurement tool.

PMID- 25975860
TI  - The early-career consultation psychiatrist: early contributions to academic
      writing.

PMID- 25975861
TI  - Don't Feed the "Krokodil": Desomorphine Fear Outpaces Reality.

PMID- 25975862
TI  - Sertraline-induced microscopic colitis.

PMID- 25975863
TI  - Suicide in systemic lupus erythematosus.

PMID- 25975864
TI  - Quantum supercharger library: hyper-parallel integral derivatives algorithms for
      ab initio QM/MM dynamics.
AB  - This article describes an extension of the quantum supercharger library (QSL) to
      perform quantum mechanical (QM) gradient and optimization calculations as well as
      hybrid QM and molecular mechanical (QM/MM) molecular dynamics simulations. The
      integral derivatives are, after the two-electron integrals, the most
      computationally expensive part of the aforementioned calculations/simulations.
      Algorithms are presented for accelerating the one- and two-electron integral
      derivatives on a graphical processing unit (GPU). It is shown that a Hartree-Fock
      ab initio gradient calculation is up to 9.3X faster on a single GPU compared with
      a single central processing unit running an optimized serial version of GAMESS
      UK, which uses the efficient Schlegel method for s- and l-orbitals. Benchmark QM
      and QM/MM molecular dynamics simulations are performed on cellobiose in vacuo and
      in a 39 A water sphere (45 QM atoms and 24843 point charges, respectively) using
      the 6-31G basis set. The QSL can perform 9.7 ps/day of ab initio QM dynamics and
      6.4 ps/day of QM/MM dynamics on a single GPU in full double precision. (c) 2015
      Wiley Periodicals, Inc. 

PMID- 25975865
TI  - Introduction to the CSBio2014 special issue.

PMID- 25975866
TI  - [Iatrogenic palatine necrosis by embolization of sphenopalatine arteries during
      management of a rebel epistaxis].
AB  - INTRODUCTION: The treatment of epistaxis sometime requires an embolization. This
      may result in ischemic palate necrosis, oronasal communication and dental losses.
      The repair of these lesions is complex. OBSERVATION: A 53-year-old patient,
      suffering from high blood pressure and hypercholesterolemia, benefited from
      bilateral embolization of the sphenopalatine arteries in order to treat a
      persistent epistaxis. He developed a middle cerebral artery stroke in the
      aftermath. During the treatment of the neurological sequelae, a necrosis of the
      2/3 of the posterior aspect of the hard palate was discovered. The angio-MRI
      showed an obstruction of both sphenopalatine arteries and of their vascular
      supplies resulting in a bilateral involvement of the alveolar bone. The diagnosis
      of iatrogenic palate necrosis was made. Tissue repair was successfully achieved
      by two loco-regional flaps. The dental rehabilitation was made by mean of a
      removable prosthesis. DISCUSSION: Palatine necrosis following embolization of the
      sphenopalatine arteries is uncommon. Ischemia resulted in a loss of substance in
      form of a punch, similar to noma's lesions. It could also be a consequence of the
      vascular background. The management of these lesions is complex and calls for
      forensic reflection about the iatrogenic origin.

PMID- 25975867
TI  - Challenges to primary care in diagnosing and managing depression in children and
      young people.

PMID- 25975868
TI  - Cost per patient of treatment for rifampicin-resistant tuberculosis in a
      community-based programme in Khayelitsha, South Africa.
AB  - OBJECTIVES: The high cost of rifampicin-resistant tuberculosis (RR-TB) treatment
      hinders treatment access. South Africa has a high RR-TB burden, and national
      policy outlines decentralisation to improve access and reduce costs. We analysed
      health system costs associated with RR-TB treatment by drug resistance profile
      and treatment outcome in a decentralised programme. METHODS: Retrospective,
      routinely collected patient-level data were combined with unit cost data to
      determine costs for each patient in a cohort treated between January 2009 and
      December 2011. Drug costs were based on recommended regimens according to drug
      resistance and treatment duration. Hospitalisation costs were estimated based on
      admission/discharge dates, while clinic visit and diagnostic/monitoring costs
      were estimated according to recommendations and treatment duration. Missing data
      were imputed. RESULTS: Among 467 patients (72% HIV infected), 49% were
      successfully treated. Treatment was initiated in primary care for 62%, with the
      remainder as inpatients. The mean cost per patient treated was $7916 (range 260
      87,140), ranging from $5369 among patients who did not complete treatment to
      $23,006 for treatment failure. Mean cost for successful treatment was $8359 (2585
      32,506). Second-line drug resistance was associated with a mean cost of $15,567
      vs. $6852 for only first-line resistance, with the major cost difference due to
      hospitalisation. Costs are reported in 2013 USD. CONCLUSIONS: RR-TB treatment
      cost was high and varied according to treatment outcome. Despite
      decentralisation, hospitalisation remained a significant cost, particularly among
      those with more extensive resistance and those with treatment failure. These cost
      estimates can be used to model the impact of new interventions to improve patient
      outcomes.

PMID- 25975869
TI  - Laboratory evaluation of three dual rapid diagnostic tests for HIV and syphilis
      in China and Nigeria.
AB  - OBJECTIVE: To determine the laboratory-based performance and operational
      characteristics of three dual rapid diagnostic tests (RDTs) for testing HIV and
      syphilis. METHODS: Three dual RDTs (SD Bioline, Chembio, and MedMira) were
      evaluated using 1514 serum specimens archived at laboratories or collected from
      clinics in China and Nigeria to determine sensitivity and specificity, with 95%
      confidence intervals. Concordance of testing results read by two technicians,
      stability of testing results read at two time points, and test operation
      characteristics were also assessed. RESULTS: All three of the evaluated RDTs gave
      excellent performance with a combined sensitivity ranging from 99.0%-99.6% for
      HIV and 98.3%-99.0% for syphilis, and a combined specificity ranging from 97.9%
      99.0% for HIV and 97.2%-99.6% for syphilis. Concordance of testing results
      between two technicians and stability of testing results read within and one hour
      past the recommended reading period showed excellent agreement, with Kappa
      greater than or equal to 0.98. CONCLUSIONS: All the tests were found to be very
      or fairly easy to use and easy to interpret the results. Further evaluations of
      these dual RDTs with whole blood in field settings, and more studies on the
      implication of introduction of these tests in HIV and syphilis control programs
      are needed.

PMID- 25975870
TI  - Estimating disease burden of maternal syphilis and associated adverse pregnancy
      outcomes in India, Nigeria, and Zambia in 2012.
AB  - OBJECTIVE: To estimate maternal syphilis and its associated adverse pregnancy
      outcomes in India, Nigeria, and Zambia. METHODS: An online estimation tool was
      used to generate point estimates and uncertainty ranges of maternal syphilis and
      adverse pregnancy outcomes due to mother-to-child transmission (MTCT). The most
      recent data (2010-2012) on antenatal care coverage, syphilis seroprevalence, and
      syphilis screening and treatment coverage at the subnational level in India,
      Nigeria, and Zambia were used to estimate disease burden for 2012. Sensitivity
      analysis was conducted for three screening and treatment scenarios (current
      coverages, current coverages minus 20%, and ideal coverages consistent with WHO
      targets for eliminating MTCT of syphilis). RESULTS: A total of 103 960, 74 798,
      and 9072 pregnant women with probable active syphilis were estimated to occur in
      India, Nigeria, and Zambia, resulting in 53 187, 37 045, and 2973 adverse
      outcomes, respectively; approximately 1.6%, 4.8%, and 37.0% of these were averted
      under the current service coverages in India, Nigeria, and Zambia. The disease
      burden varied significantly in its subnational distribution within India and
      Nigeria, but was distributed evenly across Zambia. CONCLUSIONS: The obtained
      results suggest an ongoing, unaverted high burden of maternal syphilis and
      associated adverse outcomes in India, Nigeria, and Zambia. Screening and
      treatment for syphilis must be scaled-up significantly in these countries to
      achieve elimination of MTCT of syphilis.

PMID- 25975871
TI  - Expulsion of Nova-T380, Multiload 375, and Copper-T380A contraceptive devices
      inserted during cesarean delivery.
AB  - OBJECTIVE: To compare the expulsion rate of Nova-T380, Multiload 375, and Copper
      T380A intrauterine contraceptive devices (IUCDs) inserted during cesarean
      delivery. METHODS: A comparative randomized study was conducted between January
      1, 2013, and June 30, 2014, in three maternity centers in Egypt and Saudi Arabia.
      All women scheduled for an elective cesarean and accepting intraoperative
      insertion of an IUCD were randomly allocated to receive the Nova-T380 (group 1),
      Multiload 375 (group 2), or Cu-T380A (group 3) using a computer-generated table.
      Researchers and participants were not masked to the type of IUCD. Follow-up was
      for 1 year. The primary outcome was IUCD expulsion (complete or partial [i.e.
      displacement]). RESULTS: Each group contained 40 participants. At 1 year,
      expulsion had been reported for 5 (13%) women in group 1, 2 (5%) in group 2, and
      6 (15%) in group 3 (P>0.05 for all). The frequency of displacement was
      significantly lower in group 2 (5 [13%] participants) than in group 1 (15 [38%];
      P=0.001) and group 3 (14 [35%]; P=0.008). CONCLUSION: Despite a comparable risk
      of expulsion following IUCD insertion during cesarean delivery, the Multiload 375
      device showed the lowest risk of displacement.

PMID- 25975872
TI  - Patient-specific computational modeling of blood flow in the pulmonary arterial
      circulation.
AB  - Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the
      potential to reveal continuum metrics associated with the hemodynamic stress
      acting on the vascular endothelium. It is widely accepted that the endothelium
      responds to flow-induced stress by releasing vasoactive substances that can
      dilate and constrict blood vessels locally. The objectives of this study are to
      examine the extent of patient specificity required to obtain a significant
      association of CFD output metrics and clinical measures in models of the
      pulmonary arterial circulation, and to evaluate the potential correlation of wall
      shear stress (WSS) with established metrics indicative of right ventricular (RV)
      afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC)
      hemodynamic data and contrast-enhanced computed tomography (CT) imaging were
      retrospectively acquired for 10 PH patients and processed to simulate blood flow
      in the pulmonary arteries. While conducting CFD modeling of the reconstructed
      patient-specific vasculatures, we experimented with three different outflow
      boundary conditions to investigate the potential for using computationally
      derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload.
      SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77,
      P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the
      correlation was affected by the degree of patient specificity incorporated in the
      fluid flow boundary conditions. We found that decreasing the distal PVR alters
      the flow distribution and changes the local velocity profile in the distal
      vessels, thereby increasing the local WSS. Nevertheless, implementing generic
      outflow boundary conditions still resulted in statistically significant SAWSS
      correlations with respect to both metrics of RV afterload, suggesting that the
      CFD model could be executed without the need for complex outflow boundary
      conditions that require invasively obtained patient-specific data. A preliminary
      study investigating the relationship between outlet diameter and flow
      distribution in the pulmonary tree offers a potential computationally inexpensive
      alternative to pressure based outflow boundary conditions. 

PMID- 25975873
TI  - The diagnostic targeting of a carbohydrate virulence factor from M.Tuberculosis.
AB  - The current clinical management of TB is complicated by the lack of suitable
      diagnostic tests that can be employed in infrastructure and resource poor
      regions. The mannose-capped form of lipoarabinomannan (ManLAM) is unique to the
      surface envelope of slow-growing, pathogenic mycobacteria such as M.tuberculosis
      (M.tb) and facilitates passive invasion of mononuclear phagocytes. The detection
      of this virulence factor in urine, sputum and serum has engendered interest in
      its employment as a biomarker for M.tb infection. In this study, we utilize a
      subtractive screening methodology to engineer the first high affinity recombinant
      antibody (My2F12) with exquisite specificity for the alpha1-2 mannose linkages
      enriched in ManLAM from M.tb. My2F12 binds to pathogenic mycobacterial species
      but not fast growing non-pathogenic species. Testing on matched urine and serum
      samples from TB patients indicates that My2F12 works in patient cohorts missed by
      other diagnostic methodologies. 

PMID- 25975874
TI  - Symbiotic and antibiotic interactions between gut commensal microbiota and host
      immune system.
AB  - The human gut commensal microbiota forms a complex population of microorganisms
      that survive by maintaining a symbiotic relationship with the host. Amongst the
      metabolic benefits it brings, formation of adaptive immune system and maintenance
      of its homeostasis are functions that play an important role. This review
      discusses the integral elements of commensal microbiota that stimulate responses
      of different parts of the immune system and lead to health or disease. It aims to
      establish conditions and factors that contribute to gut commensal microbiota's
      transformation from symbiotic to antibiotic relationship with human. We suggest
      that the host-microbiota relationship has been evolved to benefit both parties
      and any changes that may lead to disease, are not due to unfriendly properties of
      the gut microbiota but due to host genetics or environmental changes such as diet
      or infection. 

PMID- 25975875
TI  - Labor epidural analgesia and the incidence of instrumental assisted delivery.
AB  - OBJECTIVE: To assess the influence of labor epidural analgesia on the course of
      labor and to determine its association with instrumental assisted delivery rate.
      MATERIALS AND METHODS: A retrospective case-control study was performed during
      2007-2011 aiming to identify the relation between epidural analgesia (EA) and
      instrumental assisted delivery (IAD) rate. All patients in whom instrumental
      assistance for delivery was applied were allocated into either case (parturients
      who received EA and had IAD) or control (parturients who did not receive EA but
      had IAD) groups. Maternal demographic data, pregnancy and delivery
      characteristics as well as neonatal short-term outcome were studied. RESULTS: A
      total of 7675 vaginal deliveries occurred during the study period and 187 (2.43%)
      patients had IAD. Vacuum extraction was applied to 67 (2.16%) parturients who
      received EA, and to 120 (2.61%) who did not. The median duration of the first
      stage of labor was 510 min in the EA group as compared to 390 min in the control
      group (P=0.001). The median duration of the second stage of labor among cases and
      controls was 60 and 40 min, respectively (P<0.0005). Cases more often had their
      labor induced by oxytocin 80.3% as compared to 58.3% among controls (P=0.003).
      There was no significant association between the use of EA and increased IAD rate
      (OR=0.81; 95% CI, 0.60-1.09). CONCLUSIONS: Labor EA did not increase the
      incidence of IAD and the risk of adverse neonatal outcomes, but was associated
      with prolonged first and second stages of labor.

PMID- 25975876
TI  - A mini volume loading test for indication of preoperative dehydration in surgical
      patients.
AB  - BACKGROUND AND OBJECTIVE: Previously, a mini volume loading test (mVLT) detected
      signs of dehydration in healthy volunteers after an overnight fast. Our objective
      was to investigate whether mVLT could indicate preoperative dehydration in
      patients after an overnight fast. MATERIALS AND METHODS: The mVLT was performed
      in 36 elective primary total knee arthroplasty patients. Each subject received
      three fluid challenges before anesthesia induction. These consisted of 5 mL/kg
      boluses of Ringer's acetate infused over 3-5 min and followed by a 5-min period
      without fluids. Invasive (arterial, venous) and noninvasive (capillary)
      measurements of hemoglobin concentration were performed before and after each
      fluid challenge, as well as after a 20-min period without fluids which followed
      the last bolus. Arterial, venous and capillary plasma dilutions were calculated
      in every data point. Dilution values were used to calculate the plasma dilution
      efficacy of each fluid challenge. RESULTS: Venous dilution was higher than
      capillary after the first fluid challenge (P=0.030), but lower than capillary
      after 20 min period following the last bolus (P=0.009). Arterial dilution was
      lower than capillary (P=0.005) after 20 min following the last bolus. Veno
      capillary and arterio-capillary plasma dilution efficacy differences decreased
      (P=0.004 and P=0.033, respectively) from positive to negative during mVLT. These
      are signs of re-hydration from pre-existing dehydration according to a
      transcapillary reflux model. CONCLUSIONS: Signs of dehydration were observed
      during mVLT in patients after pre-operative overnight fast. A revised
      transcapillary reflux model was proposed to explain the results.

PMID- 25975877
TI  - Functional (ischemic) mitral regurgitation in acute phase of myocardial
      infarction: Associated clinical factors and in-hospital outcomes.
AB  - BACKGROUND AND OBJECTIVE: Mitral regurgitation (MR) after myocardial infarction
      (MI) carries adverse prognosis. The objective of this study was to assess the
      impact of functional MR on adverse in-hospital outcomes in acute MI. MATERIALS
      AND METHODS: A total of 569 patients with first ever acute MI were divided into
      three groups: no MR, mild MR (regurgitant orifice area <0.2 cm(2)) and moderate
      severe MR group (regurgitant orifice area more or equal >0.2 cm(2)). Clinical
      profile and in-hospital outcomes were compared among the groups. RESULTS:
      Patients with increasing grade of MR were elder (P<0.001), more likely to be
      female (P=0.003), have atrial fibrillation (P<0.001), higher peak C-reactive
      protein values (P=0.001), multivessel coronary artery disease (P<0.001), and less
      likely to have dyslipidemia (P=0.029). Ejection fraction, age, atrial
      fibrillation and left ventricular end diastolic diameter index were independent
      predictors of moderate and severe MR (P<0.001). In hospital cardiac death and
      decompensated heart failure was more prevalent in moderate-severe MR group.
      CONCLUSIONS: Moderate and severe MR in acute MI is related to age, atrial
      fibrillation, increased left ventricular diastolic dimensions and decreased
      ejection fraction. Moderate and severe, but not mild MR is an important clinical
      contributor to in-hospital cardiac death.

PMID- 25975878
TI  - Correlation of magnesium deficiency with C-reactive protein in elective cardiac
      surgery with cardiopulmonary bypass for ischemic heart disease.
AB  - BACKGROUND AND OBJECTIVE: Cardiac surgery is associated with systemic
      inflammatory response, which is triggered by cardiopulmonary bypass (CPB) and
      possibly with underlying magnesium deficiency. Animal studies have shown that
      magnesium deficiency intensifies oxidative stress and inflammatory processes. We
      aimed to find a link between serum, erythrocyte, cardiac tissue magnesium
      concentration and C-reactive protein (CRP) as an inflammatory marker in patients
      undergoing elective cardiac surgery with CPB. MATERIALS AND METHODS: The data of
      27 patients undergoing elective cardiac surgery with CPB for ischemic heart
      disease were analyzed. Measurements were taken at the baseline, i.e., 24 h before
      surgery (serum magnesium, CRP); time point 1, before CPB (serum, erythrocyte and
      cardiac tissue magnesium); time point 2, after CPB (serum, erythrocyte and
      cardiac tissue magnesium), and time point 3, 15-17 h after surgery (serum,
      erythrocyte magnesium, CRP). RESULTS: There was a negative correlation between
      baseline serum magnesium and baseline CRP (P=0.009; r=-0.492), negative
      correlation between cardiac tissue magnesium at the time point 1 and baseline CRP
      (P=0.021; r=-0.443), and positive correlation between CRP at time point 3 and
      erythrocyte magnesium at time point 2 (P<0.001; r=0.637). CONCLUSIONS: The data
      of our study verify that inflammatory marker CRP and magnesium concentration in
      serum and cardiac tissue before the surgery are inversely related in patients
      undergoing elective cardiac surgery with CPB. Well-planned further studies are
      needed to evaluate the importance of underlying magnesium deficiency on the
      severity of systemic inflammatory response and postoperative complications after
      surgery with CPB.

PMID- 25975879
TI  - Lipid peroxidation and antioxidant protection in girls with type 1 diabetes
      mellitus during reproductive system development.
AB  - BACKGROUND AND OBJECTIVE: Type 1 diabetes mellitus (T1D) is found worldwide and
      is regarded as one of the main risks to human health. The objective of this study
      was to determine the state of lipid peroxidation (LPO) and antioxidant protection
      in girls with T1D type considering the stages of reproductive system development.
      MATERIALS AND METHODS: This study enrolled 56 young girls with T1D and 60 healthy
      girls (control) matched by age. The study population was divided into 3 age
      groups: prepubertal, adolescent, and juvenile. The state of LPO and antioxidant
      system was assessed using the coefficient of oxidative stress that represented
      the ratio of LPO products to general antioxidative blood activity.
      Spectrophotometric and fluorometric methods were applied. RESULTS: The results of
      our study showed increased conjugated diene (CD) and thiobarbituric acid reactant
      (TBAR) concentrations as well as a decreased reduced glutathione level in
      prepubertal girls with T1D. Adolescent girls with T1D had a significantly greater
      CD level and juvenile girls with T1D had a significantly greater TBAR level and
      lower alpha-tocopherol concentration than girls in the control group. The
      greatest coefficient of oxidative stress (1.16) was observed in the prepubertal
      period. CONCLUSIONS: The prepubertal period is characterized by the most severe
      state of lipid peroxidation process-antioxidant protection.

PMID- 25975880
TI  - Osteosynthesis of the clavicle after osteotomy in brachial plexus surgery: A
      biomechanical cadaver study.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare the biomechanical
      effects of locking plate superior and anteroinferior positioning on the
      osteosynthesis of the clavicles osteotomized obliquely. MATERIALS AND METHODS:
      Ten matched pairs of fresh cadaveric clavicles osteotomized through the mid-shaft
      obliquely were repaired with a titanium 7-hole 3.5-mm reconstruction locking
      plate in the superior or the anteroinferior position. The maximal failure loads
      and the displacement of the specimens at 166 N, 183 N, 203 N loads were recorded
      by the machine in 3-point cantilever bending. Bending failure stiffness was
      calculated between 10-150 N and 151 N to maximal bending failure loads. RESULTS:
      The mean maximal failure load was 396.2 N (SD, 117.3) for superior constructs and
      220.1 N (SD, 51.1) for anteroinferior one (P<0.05). There was significant
      difference in displacement between superior and anteroinferior plated specimens
      at 183 N (6.3 [SD, 2] vs. 9.9 [SD, 3.6]) and 203 N (6.4 [SD, 0.6] vs. 11.7 [SD,
      6.6]) loads; P<0.05). Mean bending failure stiffness between 151 N and maximal
      loads was 22.6 N/mm (SD, 13.2) for superior plates and 11 N/mm (SD, 9) for
      anteroinferior plated clavicles (P<0.05). CONCLUSIONS: The superior plating of
      obliquely osteotomized clavicles with the titanium 7-hole 3.5-mm locking
      reconstruction plate had a significantly greater biomechanical stability at fixed
      loads of 183 N and 203 N than the anteroinferior plating in the inferior directed
      cantilever bending. The superior plating osteosynthesis exhibited a significantly
      greater stiffness from 151 N to maximal bending failure loads as well.

PMID- 25975881
TI  - Nicotinic potentiation of frog retinotectal transmission in tectum layer F by
      alpha3beta2, alpha4beta2, alpha2beta4, alpha6beta2, or alpha7 acetylcholine
      receptor subtypes.
AB  - OBJECTIVE: The aim of the study was to explore the effect of semi-specific
      antagonists and agonists of the nicotinic acetylcholine receptors on the paired
      pulse facilitation and nicotinic tonic and phasic potentiation of the frog
      retinotectal synaptic transmission. MATERIALS AND METHODS: The experiments were
      performed in vivo on adult frogs, Rana temporaria. An individual retina ganglion
      cell (or its retinotectal fiber) was stimulated by current pulses delivered
      through multichannel stimulating electrode positioned on the retina. Responses to
      a discharge of a single retinal ganglion cell were recorded in the tectum by an
      extracellular carbon-fiber microelectrode positioned in the terminal arborization
      of the retinotectal fiber in the tectum layer F. The effect of the antagonists
      and agonists of the nicotinic acetylcholine receptors on the tectal responses has
      been tested. RESULTS: We found that the antagonists, MLA and DHbetaE, and
      agonists, RJR-2403 and choline, of the nicotinic acetylcholine receptors of the
      alpha3beta2, alpha4beta2, alpha2beta4, alpha6beta2 or alpha7 subtypes have had no
      effect on the phasic and tonic potentiation of the retinotectal transmission. The
      paired-pulse facilitation of the retinotectal transmission was not appreciably
      affected by the antagonists, but the choline, agonist of the alpha7 subtype
      receptor, has significantly decreased the paired-pulse facilitation. CONCLUSIONS:
      The tonic and phasic potentiation of the retinotectal transmission in the tectum
      layer F were not mediated by the receptors of alpha3beta2, alpha4beta2,
      alpha2beta4, alpha6beta2 or alpha7 subtype. The results suggest that presynaptic
      nicotinic acetylcholine receptors of the frog optic fibers are different from
      those of the mammalian optic fibers.

PMID- 25975882
TI  - Training strategy of explosive strength in young female volleyball players.
AB  - OBJECTIVE: The aim of this study was to examine the effect of an 8-week combined
      jump and ball throwing training program in the performance of upper and lower
      extremities among young female volleyball players of the high school. MATERIALS
      AND METHODS: A total of 20 young female volleyball players playing at Scholar
      Sport in High School at the district level were divided in two groups: the
      experimental group (n=10; 14.0+/-0.0 years; 1.6+/-0.1 m; 52.0+/-7.0 kg and 20.7+/
      2.4% body mass) and the control group (n=10; 13.8+/-0.4 years, 1.6+/-0.1 m;
      53.5+/-4.7 kg and 20.3+/-1.7% body mass). The experimental group received
      additional plyometric and ball throwing exercises besides their normal volleyball
      practice. The control group underwent only their regular session of training.
      RESULTS: Strength performance in the experimental group significantly improved
      (medicine ball and volleyball ball throwing: P=0.00; and counter movement jump:
      P=0.05), with the improvement ranging from 5.3% to 20.1%. No significant changes
      in strength performance were observed in the control group (P>0.05). CONCLUSIONS:
      The 8-week combined jump and ball throwing training can significantly improve
      muscular performance in young female volleyball players. These findings may be
      useful for all physical education teachers and volleyball coaches.

PMID- 25975883
TI  - Quality control on mononuclear cells collected for extracorporeal
      photochemotherapy: comparison between two UV-A irradiation devices.
AB  - Recently, MacoPharma released a new UV-A cell irradiator device (Macogenic G2)
      for extracorporeal photopheresis (ECP), smaller and lighter than the Macogenic G1
      but with no integrated cooling system. We compared the two devices at different
      working temperatures (G1 at standard irradiation temperature - 21 degrees C - and
      G2 set by purpose at 34 degrees C) in patients affected with chronic graft-versus
      host disease and chronic lung allograft dysfunction treated by ECP. We
      demonstrate that both G1 and G2 devices are efficient in inducing the inhibition
      of lymphocytic proliferation and mononuclear cells apoptosis after 48 h even when
      G2 is set at higher-than-standard temperature.

PMID- 25975884
TI  - Racial and Ethnic Differences in Antipsychotic Medication Use Among Children
      Enrolled in Medicaid.
AB  - OBJECTIVE: The objective of this study was to detect and measure differences in
      antipsychotic drug use across racial-ethnic groups of children enrolled in
      Medicaid. METHODS: The main data sources were the Medicaid MAX Person Summary and
      the MAX Prescription Drug files for calendar years 2005-2009 and the
      Environmental Scanning and Program Characteristics Database. The analyses were
      based on the entire population (5.8 million) of Medicaid-enrolled children and
      adolescents, ages two to 20, from eight states. Proportional hazard and ordinary
      least-squares multivariate regressions were used to assess the effect of race
      ethnicity on the likelihood of antipsychotic prescription fills and the use of
      any psychiatric services. RESULTS: The study found robust and statistically
      significant evidence of higher antipsychotic drug use among white children,
      especially relative to Hispanic and Asian children. When analyses held all
      variables constant, the probability of having an antipsychotic fill was lower
      compared with whites by 1.8 percentage points for African Americans, by 2.0
      percentage points for Asians, and by 1.8 percentage points for Hispanics. These
      effects are large in light of the finding that the probability of an
      antipsychotic prescription fill across child-years was only 2.4%. Children from
      these minority groups were also less likely to receive psychiatric services.
      CONCLUSIONS: Substantial racial-ethnic differences were found in antipsychotic
      use. Explanations based on greater aversion to pharmacological treatment among
      minority groups are insufficient to explain the phenomenon.

PMID- 25975885
TI  - Improving Service Coordination and Reducing Mental Health Disparities Through
      Adoption of Electronic Health Records.
AB  - Despite widespread support for removing barriers to the use of electronic health
      records (EHRs) in behavioral health care, adoption of EHRs in behavioral health
      settings lags behind adoption in other areas of health care. The authors discuss
      barriers to use of EHRs among behavioral health care practitioners, suggest
      solutions to overcome these barriers, and describe the potential benefits of EHRs
      to reduce behavioral health care disparities. Thoughtful and comprehensive
      strategies will be needed to design EHR systems that address concerns about
      policy, practice, costs, and stigma and that protect patients' privacy and
      confidentiality. However, these goals must not detract from continuing to
      challenge the notion that behavioral health and general medical health should be
      treated as separate and distinct. Ultimately, utilization of EHRs among
      behavioral health care providers will improve the coordination of services and
      overall patient care, which is essential to reducing mental health disparities. 

PMID- 25975887
TI  - Short- and Long-Term Outcomes of Mental Health Court Participants by Psychiatric
      Diagnosis.
AB  - OBJECTIVE: The goal of mental health courts (MHCs) is to decrease incarceration
      and recidivism while increasing continuity of mental health treatment. Although
      previous research has found positive outcomes, questions remain unanswered
      regarding the population for which MHCs work best. No studies have assessed
      potential differences in MHC outcomes by psychiatric diagnosis. This study filled
      the gap by addressing the following research question: Are there differences in
      short-term program outcomes and in long-term recidivism and mental health
      engagement outcomes by psychiatric diagnosis? METHODS: The study was a cross-site
      evaluation of eight MHCs in a single state. To assess long-term outcomes, this
      study analyzed data from participants who had been discharged from an MHC for at
      least one year (N=234). Four diagnostic categories were used: bipolar disorder,
      depressive disorder, schizophrenia, and "other" disorder. Demographic,
      programmatic, recidivism, and mental health treatment data for each individual
      were collected from state administrative agencies. RESULTS: The findings suggest
      no differences by diagnosis in short-term outcomes or recidivism; however,
      significant reductions in use of high-intensity mental health services were noted
      for individuals with schizophrenia. CONCLUSIONS: Findings support inclusive
      eligibility for MHC participation across diagnostic categories and should inform
      policy and practice in regard to MHC development and operation. Future research
      should examine other key characteristics to determine ways in which resources can
      be best utilized.

PMID- 25975888
TI  - Characteristics and Use of Services Among Literally Homeless and Unstably Housed
      U.S. Veterans With Custody of Minor Children.
AB  - OBJECTIVE: The study examined the number of homeless veterans with minor children
      in their custody ("children in custody"), compared sociodemographic and clinical
      characteristics among homeless veterans with and without children in custody, and
      observed differences in referral and admission patterns among veterans with and
      without children in custody for a variety of U.S. Department of Veterans Affairs
      (VA) programs for homeless veterans. METHODS: Data were obtained from the VA
      Homeless Operations Management and Evaluation System for 89,142 literally
      homeless and unstably housed veterans. Sociodemographic, housing, health, and
      psychosocial characteristics of veterans were analyzed. RESULTS: Among literally
      homeless veterans, 9% of men and 30% of women had children in custody; among
      unstably housed veterans, 18% of men and 45% of women had children in custody.
      Both male and female veterans with children in custody were younger and less
      likely to have chronic general medical conditions and psychiatric disorders
      compared with other veterans, but, notably, 11% of homeless veterans with
      children in custody had psychotic disorders. Veterans with children in custody
      were more likely than other veterans to be referred and admitted to the VA's
      permanent supported housing program, and women were more likely than men to be
      admitted to the program. CONCLUSIONS: A substantial proportion of homeless
      veterans served by the VA have severe mental illness and children in custody,
      which raises concerns about the parenting environment for their children.
      Particular focus should be directed at VA's supported-housing program, and the
      practical and ethical implications of serving homeless parents and their children
      need to be considered.

PMID- 25975886
TI  - Barriers to and Facilitators in the Implementation of Cognitive-Behavioral
      Therapy for Youth Anxiety in the Community.
AB  - OBJECTIVE: The study examined, from the perspective of therapists, the barriers
      to and facilitators in implementing cognitive-behavioral therapy (CBT) for
      anxious youths in community settings. METHODS: Fifty therapists (43% of the
      original training sample of 115 providers) participated in a follow-up interview
      two years after training and consultation. They reported on barriers to and
      facilitators in implementation of CBT for youths with anxiety. RESULTS:
      Qualitative analyses identified numerous barriers and facilitators, including
      client factors (for example, motivated clients facilitated the use of CBT,
      whereas clients with complex issues and numerous psychosocial stressors hindered
      its use), intervention factors (the structure of CBT helped facilitate its use
      for some providers, whereas others reported feeling constrained by such
      structure), and organizational factors (for example, the absence of support
      within one's institution served as a barrier, whereas supervision supporting the
      use of CBT facilitated implementation). CONCLUSIONS: Findings of this
      implementation trial align with conceptual implementation frameworks and may
      guide the tailoring of future implementation efforts in order to overcome
      barriers and maximize facilitators.

PMID- 25975889
TI  - Use of Mental Health Services by Children Ages Six to 11 With Emotional or
      Behavioral Difficulties.
AB  - OBJECTIVE: The authors reported use of mental health services among children in
      the United States between ages six and 11 who were described by their parents as
      having emotional or behavioral difficulties (EBDs). METHODS: Using data from the
      2010-2012 National Health Interview Survey, the authors estimated the national
      percentage of children ages six to 11 with serious or minor EBDs (N=2,500) who
      received treatment for their difficulties, including only mental health services
      other than medication (psychosocial services), only medication, both psychosocial
      services and medication, and neither type of service. They calculated the
      percentage of children who received school-based and non-school-based
      psychosocial services in 2011-2012 and who had unmet need for psychosocial
      services in 2010-2012. RESULTS: In 2010-2012, 5.8% of U.S. children ages six to
      11 had serious EBDs and 17.3% had minor EBDs. Among children with EBDs, 17.8%
      were receiving both medication and psychosocial services, 28.8% psychosocial
      services only, 6.8% medication only, and 46.6% neither medication nor
      psychosocial services. Among children with EBDs in 2011-2012, 18.6% received
      school-based psychosocial services only, 11.4% non-school-based psychosocial
      services only, and 17.3% both school- and non-school-based psychosocial services.
      In 2010-2012, 8.2% of children with EBDs had unmet need for psychosocial
      services. CONCLUSIONS: School-age children with EBDs received a range of mental
      health services, but nearly half received neither medication nor psychosocial
      services. School-based providers played a role in delivering psychosocial
      services, but parents reported an unmet need for psychosocial services among some
      children.

PMID- 25975891
TI  - The Role of Mental Health Services in Addressing HIV Infection Among Women With
      Serious Mental Illness.
AB  - OBJECTIVE: This article reviews how mental health services can best prevent and
      treat HIV infection among women with serious mental illness. METHODS: This is a
      selective narrative review of the recent literature on mental health services and
      HIV. The author used the terms "HIV," "serious mental illness," and "women" to
      search Google Scholar. RESULTS: Out of 500 relevant papers retrieved, 82 were
      included, based on their state-of-the-art findings. Women with serious mental
      illness at risk of HIV were found to be an especially vulnerable group. The
      evidence suggests that discussion of the modes of viral transmission reduces the
      risk of infection in this population, as do psychoeducation; long-term
      antipsychotic medication; adherence therapy; community treatment orders;
      prevention of domestic violence and homelessness; disbursement of financial
      entitlements; provision of psychotherapy and social support; cognitive
      rehabilitation; promotion of abstinence, monogamy, or reduction in the number of
      sexual partners; access to and training in the use of condoms; prophylaxis with
      vaginal microbicides and oral antiretroviral drugs; prompt diagnosis and
      treatment of sexually transmitted diseases; across-the-board offers of HIV
      testing; and preservation and monitoring of reproductive health. For HIV-positive
      individuals, comprehensive treatment measures have included prompt HIV treatment;
      long-term retention in care; supervision of medication adherence and drug
      interactions; rapid management of substance use disorders and all other
      comorbidities as well as drug side effects; and preclusion of professional
      stigmatization. CONCLUSIONS: There is now sufficient evidence to recommend
      effective combinations of strategies to prevent and treat HIV within mental
      health services.

PMID- 25975890
TI  - Characterizing the Mental Health Care of U.S. Cambodian Refugees.
AB  - OBJECTIVE: This study examined U.S. Cambodian refugees' utilization of mental
      health services across provider types, levels of minimally adequate care, and
      mode of communication with providers. METHODS: Face-to-face household interviews
      about mental health service use in the past 12 months were conducted as part of a
      study of a probability sample of Cambodian refugees. The analytic sample was
      restricted to the 227 respondents who met past 12-month criteria for
      posttraumatic stress disorder (PTSD) or major depressive disorder or both.
      Analyses were weighted to account for complex sampling design effects and for
      attrition. RESULTS: Fifty-two percent of Cambodian refugees who met diagnostic
      criteria obtained mental health services in the past 12 months. Of those who
      obtained care, 75% visited a psychiatrist and 56% a general medical provider.
      Only 7% had obtained care from other mental health specialty providers. Virtually
      all respondents who had seen a psychiatrist (100%) or a general medical doctor
      (97%) had been prescribed a psychotropic medication. Forty-five percent had
      received minimally adequate care. Most relied on interpreters to communicate with
      providers. CONCLUSIONS: Cambodian refugees' rates of mental health service
      utilization and minimally adequate care were comparable to those of individuals
      in the general U.S. POPULATION: Cambodian refugees obtained care almost entirely
      from psychiatrists and general medical doctors, and nearly all were receiving
      pharmacotherapy; these findings differ from rates seen in a nationally
      representative sample. Given this pattern of utilization, and the persistently
      high levels of PTSD and depression found among Cambodian refugees, treatment
      improvements may require identification of creative approaches to delivering more
      evidence-based psychotherapy.

PMID- 25975892
TI  - Decreased Mortality Rates of Inmates With Mental Illness After a Tobacco-Free
      Prison Policy.
AB  - OBJECTIVE: Negative health consequences of smoking have prompted many
      correctional facilities to become tobacco free, including the New Jersey
      Department of Corrections, and this study examined the results of implementing
      tobacco-free policies. METHODS: Mortality rates in the total population of
      inmates and in a subgroup with identified special mental health needs or mental
      illnesses (referred to in this article as persons with special needs) were
      measured from January 2005 through June 2014, a period during which tobacco use
      was significantly reduced and then eliminated. RESULTS: The total mortality rate
      of all causes of death combined was three times higher for persons with special
      needs in 2005 compared with those without special needs. The total annual
      mortality rate decreased by 13%, from 232 to 203 per 100,000 population between
      2005 and 2013. The mortality rate for persons identified as having special needs
      decreased by 48%, from an average of 676 per 100,000 population over the eight
      year period before the ban to 353 per 100,000 in the 18 months after the ban.
      Reduced mortality among persons with special needs between 2005 and 2014 in half
      year increments was correlated with the reduction and elimination of tobacco
      products (median bootstrapped Pearson r=.60, 95% confidence interval [CI] =.21 to
      .86). In strong contrast, however, the bootstrapped correlation between the
      mortality rate of persons not identified as having special needs and tobacco
      sales over the same period was not significant (median Pearson r=-.13, CI=-.50 to
      .28). No other major medical intervention occurred during these years.
      CONCLUSIONS: This striking correlation of quick and substantial reduction of
      mortality among individuals with a mental illness in association with the
      reduction and subsequent ban of smoking suggests that smoking may play a major
      role in the reduced life span of persons with mental illness.

PMID- 25975893
TI  - Influence of Criminal Justice Involvement and Psychiatric Diagnoses on Treatment
      Costs Among Adults With Serious Mental Illness.
AB  - The impact of criminal justice involvement and clinical characteristics on the
      cost of public treatment services for adults with serious mental illnesses is
      unknown. The authors examined differential effects of justice involvement on
      behavioral health treatment costs by primary psychiatric diagnosis (schizophrenia
      or bipolar disorder) and also by substance use diagnosis among 25,133 adult
      clients of Connecticut's public behavioral health system in fiscal years 2006 and
      2007. Justice-involved adults with schizophrenia had the highest costs, strongly
      driven by forensic hospitalizations. Addressing the cross-system burdens of
      forensic hospitalizations may be a sensible starting point in the effort to
      reduce costs in both the public behavioral health and justice systems. 

PMID- 25975895
TI  - Oncological whole-body staging in integrated (18)F-FDG PET/MR: Value of different
      MR sequences for simultaneous PET and MR reading.
AB  - OBJECTIVE: To evaluate different magnetic resonance (MR) imaging sequences in
      integrated positron emission tomography (PET)/MR concerning their ability to
      detect tumors and allocate increased radionuclide uptake on (18)F
      fluorodeoxyglucose ((18)F-FDG) PET in intraindividual comparison with computed
      tomography (CT) from PET/CT. MATERIAL AND METHODS: Sixty-one patients (34 female,
      27 male, mean age 57.6 y) who were examined with contrast-enhanced PET/CT and
      subsequent PET/MR (mean delay for PET/MR after injection: 147 +/- 43 min) were
      included. A maximum of ten (18)F-FDG-avid lesions per patient were analyzed on CT
      from PET/CT and with the following MR sequences from PET/MR: T2, turbo inversion
      recovery magnitude (TIRM), non-enhanced T1, contrast-enhanced T1, and diffusion
      weighted imaging (DWI). All lesions were rated using a four-point ordinal scale
      (scored from 0 to 3) concerning visual detectability of the lesion against the
      surrounding background and anatomical allocation of the PET finding. In each
      category (detectability and allocation), Wilcoxon rank sum tests were performed.
      Bonferroni-Holm correction was performed to prevent alpha-error accumulation.
      RESULTS: In 225 (18)F-FDG-avid lesions (156 confirmed as malignant by
      radiological follow up, 69 by histopathology), visual detectability was
      comparably high on CT (mean: 2.5 +/- 0.9), TIRM (mean: 2.5 +/- 0.9), T2 (mean:
      2.4 +/- 0.9), and DWI (mean: 2.5 +/- 1.0) and was significantly higher than on
      non-enhanced T1 (mean: 2.2 +/- 1.0). While anatomic allocation of the PET finding
      was comparable with CT (mean: 2.6 +/- 0.7), T2 (mean: 2.6 +/- 0.7), and TIRM
      (mean: 2.8 +/- 0.7), it was significantly higher compared to DWI (mean: 2.1 +/-
      1.0) and non-enhanced T1 (mean: 2.4 +/- 0.8). CONCLUSION: In conclusion, T2,
      TIRM, and contrast-enhanced T1 provide a high quality of lesion detectability and
      anatomical allocation of FDG-avid foci. Their performance is at least comparable
      to contrast-enhanced PET/CT. Non-enhanced T1 may be omitted and the necessity of
      DWI should be further investigated for specific questions, such as assessment of
      the liver.

PMID- 25975894
TI  - LINEs in mice: features, families, and potential roles in early development.
AB  - Approximately half of the mammalian genome is composed of repetitive elements,
      including LINE-1 (L1) elements. Because of their potential ability to transpose
      and integrate into other regions of the genome, their activation represents a
      threat to genome stability. Molecular pathways have emerged to tightly regulate
      and repress their transcriptional activity, including DNA methylation, histone
      modifications, and RNA pathways. It has become evident that Line-L1 elements are
      evolutionary diverse and dedicated repression pathways have been recently
      uncovered that discriminate between evolutionary old and young elements, with RNA
      directed silencing mechanisms playing a prominent role. During periods of
      epigenetic reprogramming in development, specific classes of repetitive elements
      are upregulated, presumably due to the loss of most heterochromatic marks in this
      process. While we have learnt a lot on the molecular mechanisms that regulate
      Line-L1 expression over the last years, it is still unclear whether reactivation
      of Line-L1 after fertilization serves a functional purpose or it is a simple side
      effect of reprogramming. 

PMID- 25975896
TI  - The image quality and lesion characterization of breast using automated whole
      breast ultrasound: A comparison with handheld ultrasound.
AB  - OBJECTIVE: To prospectively evaluate the image quality of automated whole breast
      ultrasonography (AWUS) in the characterization of breast lesions compared with
      handheld breast ultrasonography (HHUS). MATERIALS AND METHODS: This prospective
      study included a total of 411 lesions in 209 women. All patients underwent both
      HHUS and AWUS prior to biopsy. An evaluation of identical image pairs of 411
      lesions obtained from both modalities was performed, and the image quality of
      AWUS was compared with that of HHUS as a reference standard. The overall image
      quality was evaluated for lesion coverage, lesion conspicuity, and artifact
      effect using a graded score. Additionally, the factors that correlated with
      differences in image quality between the two modalities were analyzed. RESULTS:
      In 97.1%, the image quality of AWUS was identical or superior to that of HHUS,
      whereas AWUS was inferior in 2.9%. In only 0.5%, the poor quality of AWUS images
      caused by incomplete lesion coverage and shadowing due to a contact artifact
      inhibited precise interpretations. The two main causes resulting in degraded AWUS
      image quality were blurring of the margin (83.3%) and acoustic shadowing by
      Cooper's ligament or improper compression pressure of the transducer (66.7%).
      Among various factors, peripheral location from the nipple (p=0.01), lesion size
      (p=0.02), shape descriptor (p=0.02), and final American College of Radiology
      Breast Imaging Reporting and Data System (BI-RADS) category (p=0.001) were
      correlated with differences in image quality between AWUS and HHUS. CONCLUSION:
      Although the image quality of AWUS was comparable to that of HHUS for lesion
      interpretation, HHUS was clearly superior to AWUS for analyzing lesions with a
      peripheral location, an irregular shape, a non-circumscribed margin and BI-RADS
      category 4 or 5.

PMID- 25975897
TI  - The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim
      Chester disease.
AB  - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocitosis,
      characterized by multisystemic xanthogranulomatous infiltration by foamy
      histiocytes that stain positively for CD68 marker but not express CD1a and S100
      proteins. Etiology and pathogenesis are still unknown and only about 500 cases
      are related in the literature. Multisystemic involvement leads to a wide variety
      of clinical manifestations that results in a poor prognosis although recent
      advances in treatment. We present the clinical, nuclear medicine findings and
      therapeutic aspects of a serie of 6 patients with histopathological diagnosis of
      ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose
      (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)
      PET/CT was performed in one case. Three different presentations of the disease
      were observed in our casuistic: most indolent form was a cutaneous confined
      disease, presented in only one patient. Multifocal involvement with central
      nervous system (CNS) preservation was observed in two patients. Most aggressive
      form consisted in a systemic involvement with CNS infiltration, presented in
      three patients. In our experience neurological involvement, among one case with
      isolate pituitary infiltration, was associated with mortality in all cases. 18FDG
      PET/CT and BS were particularly useful in despite systemic involvement; locate
      the site for biopsy and the treatment response evaluation. By our knowledge,
      18FDOPA-PET/CT not seems useful in the initial staging of ECD. A baseline 18FDG
      PET/CT and BS may help in monitoring the disease and could be considered when
      patients were incidentally diagnosed and periodically 18FDG-PET/CT must be
      performed in the follow up to evaluate treatment response. 

PMID- 25975898
TI  - Expression of peroxiredoxins and thioredoxins in the mouse spinal cord during
      embryonic development.
AB  - Reactive oxygen and nitrogen species (ROS/RNS) are natural byproducts of cellular
      metabolism. Although these molecules are deleterious at high concentrations,
      moderate levels of ROS/RNS are essential for normal cell function and take part
      in numerous cellular processes. The regulation of ROS/RNS is largely attended by
      peroxiredoxins (Prdxs) and their main reductants, thioredoxins (Trxs). Through
      their oxidoreductase activities, the members of the Trx/Prdx system can also
      affect certain cellular processes, notably many implicated in central nervous
      system (CNS) development. Although several studies have investigated the
      expression of Prdxs and Trxs in mouse, rat, and human adult CNS, few data are
      available concerning embryonic stages. In this work, we use immunofluorescence
      analyses to study the distribution of these enzymes during prenatal mouse spinal
      cord development. Our results highlight several patterns that contrast with
      available data for the adult. Indeed, Prdx1, Prdx4, and Prdx6, which are
      expressed in glial cells in the adult CNS, present clear neuronal localization in
      mouse spinal cord during embryonic development. Additionally, Prdx1, Prdx2, and
      to a lesser extent Prdx4, Prdx6, and Trx1 are localized mainly in the nucleus of
      neural cells. Finally, we identified a consistent, intense expression of all
      Prdxs and Trxs in groups of cells located in ventral regions of the spinal cord
      that express motor neuronal markers. These striking expression patterns suggest
      novel functions of these enzymes at these stages and offer clues to the role of
      the Trx/Prdx system during embryonic development of the spinal cord.

PMID- 25975899
TI  - Transmission electron microscopy finds plenty of room on the surface.
AB  - The atomic features of materials' surfaces have fundamental importance for
      applications in numerous fields, such as heterogeneous catalysis, energy
      conversion and thin-film growth. Now transmission electron microscopy (TEM) and
      affiliated techniques have thoroughly revolutionized many disciplines of natural
      sciences, and are becoming some of the best solutions for surface exploration. In
      this Perspective, we try to summarise the important progress in surface
      elucidation by applying the state-of-the-art TEM, which covers (1) from the
      essential features of oxides to their dynamic behaviors, and the interactions
      between surfaces and gases; (2) the visualization of emerging materials from zero
      dimensional single atoms to two-dimensional materials, and the development
      towards an ultimate integration of three-dimensional surfaces. Plenty of room has
      been made for TEM exploration of a material's surface, and the surface-integral
      frontiers are being pushed further. 

PMID- 25975900
TI  - [Strengthening the standardization of breast pathology].

PMID- 25975901
TI  - [Review of Guideline for Detection of HER2 in Breast Cancer (2014) after one-year
      release].

PMID- 25975902
TI  - [Antibodies in the immunohistochemical detection of estrogen and progesterone
      receptor status in breast carcinoma].

PMID- 25975903
TI  - [Pathology of breast carcinomas after neoadjuvant chemotherapy: an expert
      consensus].

PMID- 25975904
TI  - [Guideline for testing of estrogen and progesterone receptors in breast cancer].

PMID- 25975905
TI  - [Correlation between the methylation status of Runx3 gene and positive expression
      of estrogen receptor in breast cancer].
AB  - OBJECTIVE: To investigate the relationship between hypermethylation of Runx3 gene
      promoter and estrogen receptor (ER) and the implications of Runx3 gene promoter
      hypermethylation in ER positive breast cancer. METHODS: Western blot and RT-PCR
      were used to detect the protein and mRNA expression of Runx3 gene in breast
      cancer cell lines (MCF7 and SKBR3) and normal breast epithelium cell line
      (MCF10A). Immunohistochemical SP method was used to detect the expression of ER
      and Runx3 proteins in 113 tissue samples of breast cancer. Moreover, methylation
      specific PCR was used to detect RUN3 promoter methylation in cell lines MCF7,
      SKBR3, MCF10A and 113 tissue samples of breast cancer. RESULTS: Of the 3 cell
      lines, Runx3 protein and mRNA were detectable in MCF10A, but were absent in MCF7
      and SKBR3. MCF7 had a high methylation status at Runx3 promoter, in contrast,
      MCF10A and SKBR3 showed unmethylated RUN3 promoter. Among the 113 cases of breast
      cancer, 68 cases were ER positive and 45 were negative. The positive rates of
      Runx3 protein expression in ER positive and negative tumors were 26.5% (18/68)
      and 66.7% (30/45), respectively (P<0.05). Runx3 promoter hypermethylation was
      seen in 82.4% (56/68) of ER positive breast cancer cases and 22.2% (10/45) of ER
      negative ones (P<0.05). Among 68 cases of ER positive cases, Runx3 promoter
      hypermethylation was positively correlated with the clinical tumor stage
      (OR=5.84, P<0.05). CONCLUSIONS: Runx3 gene promoter hypermethylation is present
      mainly in the ER positive breast cancers. Testing of Runx3 promoter methylation
      may provide additional reference for clinical stage and prognosis of breast
      cancer patients, especially in those with ER positive tumors.

PMID- 25975906
TI  - [Analysis of prognostic parameters in patients with breast cancer of size smaller
      than or equal to 2 cm].
AB  - OBJECTIVE: To study the prognostic parameters in patients with breast cancer of
      size smaller than or equal to 2 cm which are useful for treatment and follow-up.
      METHODS: Four hundred and seventy-five patients with breast cancer of size
      smaller than or equal to 2 cm diagnosed and treated in Affiliated Union Hospital,
      Fujian Medical University, China during the period from January, 2002 to
      December, 2008 were enrolled into the study. The clinical features, pathologic
      findings and follow-up data were analyzed. Kaplan-Meier curve method and Cox
      proportional hazard regression model were used to study factors which influenced
      disease-free survival and overall survival of the patients. RESULTS: Onset below
      40 years of age (P=0.000), presence of axillary lymph node metastasis (P=0.000)
      and histologic grade 3 (P=0.013) negatively correlated with 5-year disease-free
      survival. Onset below 40 years of age (P=0.000), presence of axillary lymph node
      metastasis (P=0.000), histologic grade 3 (P=0.012) and negative estrogen receptor
      status (P=0.035) negatively correlated with 5-year overall survival. Multivariate
      analysis indicated that onset below 40 years of age (HR=3.249, 95% CI: 1.514
      6.974, P=0.002) and presence of axillary lymph node metastasis (HR=3.177, 95% CI:
      1.695-5.953, P=0.000) were independent predictors of 5-year disease-free
      survival. Onset below 40 years of age (HR=5.006, 95% CI: 2.013-12.449, P=0.001),
      presence of axillary lymph node metastasis (HR=4.461, 95% CI: 1.948-10.218,
      P=0.000) and negative estrogen receptor status (HR=2.612, 95% CI: 1.092-6.246,
      P=0.031) were independent predictors of 5-year overall survival. CONCLUSIONS:
      Onset below 40 years of age, presence of axillary lymph node metastasis and
      negative estrogen receptor status are prognostic indicators in patients with
      breast cancer of size less than or equal to 2 cm. Assessment of these prognostic
      parameters would be helpful in treatment and follow-up of this group of breast
      cancer patients.

PMID- 25975907
TI  - [Significance of carbonic anhydrase IX protein in fibrotic foci of mammary
      invasive ductal carcinomas].
AB  - OBJECTIVE: To study the relationship between fibrotic focus (FF) and carbonic
      anhydrase (CA) IX in invasive ductal carcinomas (IDC) of the breast. METHODS: In
      167 cases of IDC, the FF was assessed morphologically, and expression of ER, PR
      and CA IX was evaluated using MaxVision immunohistochemistry. RESULTS: The
      expression of CA IX in IDC with and without FF was 56.3% (45/80) and 28.7%
      (25/87) respectively, with significant difference (P=0.001). In IDC with FF, the
      CA IX expression of tumor cells in tumors with CA IX-positive fibroblasts (35/40,
      87.5%) was significantly (P<0.001) higher than that in tumors with CA IX-negative
      fibroblasts (10/40, 25.0%). In IDC with FF, the CA IX expression of fibroblasts
      of FF in grade 3 IDC (23/33, 69.7%) was significantly (P=0.006) higher than that
      in grade 1+2 tumors (17/47, 36.2%). The ER and PR expression of tumor cells in
      tumors containing CA IX-negative fibroblasts was 72.5% (29/40) and 65.0% (26/40)
      respectively, whereas the ER and PR expression of tumor cells in tumors
      containing CA IX-positive fibroblasts was 50.0% (20/40) and 42.5% (17/40)
      respectively; the difference was statistically significant (for both ER and PR,
      P=0.04). The age of patients with tumors containing CA IX-negative fibroblasts
      was significantly (P=0.002) older than those containing CA IX-positive
      fibroblasts. The FF diameter/tumor diameter in tumors containing CA IX-positive
      fibroblasts was significantly larger than those containing CA IX-negative
      fibroblasts. (3) For the groups of tumor size<=2 cm and tumor size between 2 cm
      to 5 cm, the diameter of the fibrotic focus was significantly (P<0.01) smaller
      than the fibrotic focus size of tumors>5 cm in size. CONCLUSIONS: CA IX
      expression is correlated with FF, and that in fibroblasts of FF correlated with
      patients' age, tumor grade, hormone receptors and FF diameter/tumor diameter. CA
      IX expression in FF might be a marker for poor prognosis in patients with breast
      cancer.

PMID- 25975908
TI  - [Detection of KRAS,NRAS and BRAF gene mutations in colorectal carcinoma].
AB  - OBJECTIVE: To investigate mutations frequencies of KRAS,NRAS and BRAF genes in
      colorectal carcinoma. METHODS: Tissue specimens from 200 colorectal cancer
      patients at diagnosis were collected and subject to KRAS,NRAS and BRAF mutation
      analyses by PCR-based direct DNA sequencing targeting exons 2, 3 and 4 of KRAS
      gene, exons 2, 3 and 4 of NRAS gene and exon 15 of BRAF gene. RESULTS: Activating
      mutations were detected in KRAS (44%, 88/200), NRAS (2%, 4/200) and BRAF (5%,
      10/200) in this study cohort.Among KRAS mutations, 64.8% (57/88) occurred in
      codon 12 and 12.5% (11/88) occurred in codon 13. KRAS gene mutation in exon 3
      mainly involved codons 59 and 61. KRAS gene mutation in exon 4 mainly involved
      codons 117 and 146. CONCLUSIONS: Mutations at exon 2 of KRAS gene have the
      highest frequency in colorectal carcinoma. Expanding the detection sites of KRAS
      gene combined with NRAS and BRAF genes may help to identify patients who will
      most likely benefit from targeted therapies.

PMID- 25975909
TI  - [Clinicopathologic analysis of 254 cases of papillary thyroid microcarcinoma].
AB  - OBJECTIVE: To evaluate the prognostic impact of tumor size, ultrasonography,
      central neck lymph node involvement, and age of patients in papillary thyroid
      microcarcinoma (PTMC). METHODS: Two hundred and fifty-four patients who underwent
      total thyroidectomy and central neck dissection for PTMC between 2012 and 2014
      were included in this retrospective study. Statistical correlation between tumor
      size and various clinicopathological parameters was assessed by univariate and
      multivariate analyses. The ultrasound findings were also evaluated. RESULTS: A
      total of 254 patients (199 females and 55 males) were included in this study.
      PTMC showed a predilection for female patients, 41-50 years of age (43.3% of all
      cases, 110/254), and ultrasound showed hypoechoic nodules. Statistically
      significant correlation was demonstrated between central neck lymph node
      involvement and the following factors: age and tumor size. A tumor diameter
      greater than 0.5 mm (67.3% of all cases) most commonly occurred in patients older
      than 41 years, and was associated with a higher risk of metastatic central neck
      lymph node involvement (P<0.05). Hashimoto's thyroiditis was noted in the
      background in 39.4%(100/254) of cases. CONCLUSIONS: Tumor size appears to have a
      prognostic impact in PTMC, and larger size is more likely to be associated with a
      higher risk of central neck lymph node involvement. It is controversial whether
      the etiology of papillary thyroid carcinoma is related to Hashimoto's
      thyroiditis.

PMID- 25975910
TI  - [Detection of p16 by fluorescence in-situ hybridization and immunohistochemistry
      in malignant mesothelioma].
AB  - OBJECTIVE: To study the role of p16 gene mutation status as detected by
      fluorescence in-situ hybridization (FISH) and p16 protein expression as detected
      by immunohistochemistry in differential diagnosis of malignant mesothelioma and
      benign mesothelial hyperplasia. METHODS: p16 gene mutation status and protein
      expression were detected by FISH and immunohistochemistry respectively in 55
      cases of pleural malignant mesothelioma and 30 cases of benign mesothelial
      hyperplasia. RESULTS: FISH study showed that the rate of p16 deletion in
      malignant mesothelioma (81.8%,45/55) was higher than that in benign mesothelial
      hyperplasia (3.3%,1/30). The difference was statistically significant (P<0.05).
      Immunohistochemical study showed that the rate of p16 protein expression in
      malignant mesothelioma (23.6%) was lower than that in benign mesothelial
      hyperplasia (76.7%). The difference was also statistically significant. The
      sensitivity and specificity of FISH in distinguishing between mesothelioma and
      reactive mesothelial hyperplasia were higher than those of immunohistochemistry.
      CONCLUSIONS: In contrast to reactive mesothelial hyperplasia, p16 gene is deleted
      and p16 protein is not expressed in malignant mesothelioma. The sensitivity and
      specificity of FISH are higher than those of immunohistochemistry in the
      distinction.

PMID- 25975911
TI  - [Congenital pulmonary airway malformation of lung in fetus: a clinicopathological
      analysis].
AB  - OBJECTIVE: To study the etiology, pathogenesis, clinicopathologic
      characteristics, prognosis and treatment of congenital pulmonary airway
      malformation (CPAM). METHODS: Eighteen cases of CPAM were enrolled into the
      study. The clinical history, autopsy findings and immunohistochemical results
      were evaluated, with review of literature. The pathogenetic mechanism, pathologic
      features and differential diagnosis of CPAM were studied. RESULTS: Histologic
      examination showed that 2 cases were classified as Stocker type I, 12 cases as
      type II, and 4 cases as type III. The lesion was unilateral and involved single
      lobe in 13 cases. The remaining 5 cases had bilateral diseases. Of the 18 cases
      studied, 12 cases showed single organ involvement and 6 cases had malformations
      affecting multiple organs. The associated malformations included cardiac
      anomalies (4 cases), polycystic kidney with gastrointestinal atresia (1 case) and
      nuchal cystic hygroma with hydrothorax (1 case). CONCLUSIONS: CPAM is a rare
      pulmonary disorder. The etiology of this non-neoplastic condition is unknown.
      Imaging analysis is a valuable tool to suggest CPAM, while definite diagnosis
      requires pathologic examination. The overall prognosis is determined by the
      presence of associated malformations, fetal hydrops and pulmonary hypoplasia.

PMID- 25975912
TI  - [Epidermal growth factor-like domain 7 promotes endothelial cell migration and
      angiogenesis by activating ERK signaling pathway].
AB  - OBJECTIVE: To explore the effect of epidermal growth factor-like domain 7(EGFL7)
      on the migration and angiogenesis of endothelial cells. METHODS: EGFL7
      overexpression vectors were constructed and transfected into human microvascular
      endothelial cells. The expression levels of EGFL7-mRNA and EGFL7 protein were
      examined by real-time RT-PCR and Western blot. Cell migration was analyzed by the
      wound healing. The capability of cell to form capillary-like tubes in vitro was
      evaluated on matrigel assay. Protein expression of p-AKT, AKT, p-ERK and ERK in
      endothelial cells was detected by Western blot upon transfection with EGFL7
      overexpression vectors and vehicle control for 0, 10, 30 and 60 min. RESULTS:
      Migration and angiogenesis of endothelial cells were notably enhanced by EGFL7
      overexpression. ERK pathway was strongly activated by EGFL7, whereas AKT remained
      constant in endothelial cells. Inhibition of ERK impaired EGFL7 induced ERK
      activation and endothelial cell migration and angiogenesis. CONCLUSION: EGFL7
      effectively promotes migration and angiogenesis through ERK signaling pathway in
      endothelial cells.

PMID- 25975913
TI  - [Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in
      melanoma].
AB  - OBJECTIVE: To study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence
      of wild type BRAF or BRAFV600E in melanoma. METHODS: Melanoma cells harboring
      BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe
      puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT,
      followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells
      harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus
      to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1
      and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were
      infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1
      and p-ERK expression. RESULTS: In melanoma cells harboring BRAFWT genotype and
      transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK
      levels were notably reduced as compared to either negative control or empty
      vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro
      GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either
      negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines
      led to an increased ERK activity. However, there was no significant change of ERK
      activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK
      in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show
      any significant difference from either negative control or empty vector.
      CONCLUSIONS: Based on these findings, it suggests that there exists an auto
      regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK
      signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of
      Mps1 on the MAPK pathway.

PMID- 25975914
TI  - [Expression of human epidermal growth factor receptor 2 in mucinous carcinoma of
      breast].

PMID- 25975915
TI  - [Application of single-probe CISH technique on HER2 gene assessment in breast
      cancer: a comparative study].

PMID- 25975916
TI  - [Relationship between trophoblast cell-surface antigen 2 expression,
      clinicopathologic features and prognosis in colorectal carcinoma].

PMID- 25975917
TI  - [von Hippel-Lindau syndrome: a clinicopathologic analysis].

PMID- 25975918
TI  - [Primary plasmablastic plasmacytoma of breast: report of a case].

PMID- 25975919
TI  - [Angioleiomyoma with mature adipocytes of nasal vestibule: report of a case].

PMID- 25975920
TI  - [Primary mucinous carcinoma of thyroid gland: report of a case].

PMID- 25975921
TI  - [Induced pluripotent stem cells and its application in treatment of breast
      cancer].

PMID- 25975922
TI  - [Role of integrins in occurrence and development of breast cancer].

PMID- 25975924
TI  - In-vitro thrombogenicity assessment of flow diversion and aneurysm bridging
      devices.
AB  - Endoluminal devices such as metallic flow diversion (FD) and aneurysm bridging
      (AB) stents are used for treatment of intracranial aneurysms. Treatments are
      associated with thrombogenic events mandating the use of dual antiplatelet
      therapy in all cases. In the current in vitro study, we utilize a slow binding
      fluorogenic thrombin specific substrate to measure the thrombin generation
      potential of six devices: four FD devices (PipelineTM Flex embolization device,
      PipelineTM Flex embolization device with Shield TechnologyTM, SILK+, FREDTM) and
      two AB devices (SolitaireTM AB, LEO+). We show that the PipelineTM Flex
      embolization device with Shield TechnologyTM has significantly lower peak
      thrombin and takes significantly longer time to achieve peak thrombin (time to
      peak) compared to the other three FD devices (p < 0.05), with statistically
      similar results to the less thrombogenic AB devices. We conclude that surface
      modification of endoluminal stents could be an effective method to mitigate
      thrombogenic complications. 

PMID- 25975925
TI  - Uncatalysed diaryldiazo cyclopropanations on bicyclic lactams: access to
      annulated prolines.
AB  - The uncatalysed cycloaddition of substituted diaryldiazo compounds onto bicyclic
      unsaturated lactams derived from pyroglutamic acid efficiently leads to highly
      functionalised azatricyclononanes. The products are readily elaborated to
      deprotected pyroglutamate derivatives, providing rapid access to conformationally
      constrained amino acids and their analogues. Preliminary assessment of
      antibacterial activity against one Gram positive and one Gram negative organism
      indicated high levels of efficacy in some cases. 

PMID- 25975926
TI  - Negative association between parental care and sibling cooperation in earwigs: a
      new perspective on the early evolution of family life?
AB  - The evolution of family life requires net fitness benefits for offspring, which
      are commonly assumed to mainly derive from parental care. However, an additional
      source of benefits for offspring is often overlooked: cooperative interactions
      among juvenile siblings. In this study, we examined how sibling cooperation and
      parental care could jointly contribute to the early evolution of family life.
      Specifically, we tested whether the level of food transferred among siblings
      (sibling cooperation) in the European earwig Forficula auricularia (1) depends on
      the level of maternal food provisioning (parental care) and (2) is translated
      into offspring survival, as well as female investment into future reproduction.
      We show that higher levels of sibling food transfer were associated with lower
      levels of maternal food provisioning, possibly reflecting a compensatory
      relationship between sibling cooperation and maternal care. Furthermore, the
      level of sibling food transfer did not influence offspring survival, but was
      associated with negative effects on the production of the second and terminal
      clutch by the tending mothers. These findings indicate that sibling cooperation
      could mitigate the detrimental effects on offspring survival that result from
      being tended by low-quality mothers. More generally, they are in line with the
      hypothesis that sibling cooperation is an ancestral behaviour that can be
      retained to compensate for insufficient levels of parental investment.

PMID- 25975927
TI  - RNA synthetic biology: from the test tube to cells and back again.

PMID- 25975930
TI  - Incarcerated Veterans Outreach Program.
AB  - The objective of this study is to identify and facilitate re-entry services for
      military veterans in the Criminal Justice System through the Incarcerated Veteran
      Outreach Program. Veterans are explored as a subgroup of the general inmate jail
      populations in southern Ohio based upon veteran's status, military discharges,
      service-related injuries, treatment needs, pre-release planning, and re-entry
      services. Veterans reported having psycho-social problems, diverse levels of
      criminality, criminogenic needs, and significant episodes of homelessness. A
      sample of 399 incarcerated veterans in state prison, county jails, and community
      corrections setting were identified and completed the psycho-social pre-release
      assessment. Their average age was 44.6; they were more likely to be White males,
      divorced, most honorably discharged, and were represented in the following eras:
      34% Vietnam, 35% post-Vietnam, 26% Persian Gulf War, and 5% Operation Iraqi
      Freedom/Operation Enduring Freedom. The findings encourage the development of a
      re-entry outreach model and strategies to prevent episodes of criminal
      recidivism. 

PMID- 25975931
TI  - Infusion of Human Bone Marrow-Derived Mesenchymal Stem Cells Alleviates
      Autoimmune Nephritis in a Lupus Model by Suppressing Follicular Helper T-Cell
      Development.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      production of autoantibodies to components of the cell nucleus. These
      autoantibodies are predominantly produced with the help of follicular helper T
      (Tfh) cells and form immune complexes that trigger widespread inflammatory
      damage, including nephritis. In recent studies, mesenchymal stem cells (MSCs)
      elicited diverse, even opposing, effects in experimental and clinical SLE. Here
      we investigated the effect of human bone marrow-derived MSCs (hBM-MSCs) in a
      murine model of SLE, the F1 hybrid between New Zealand Black and New Zealand
      White strains (NZB/W). We found that infusion of female NZB/W mice with hBM-MSCs
      attenuated glomerulonephritis; it also decreased levels of autoantibodies and the
      incidence of proteinuria and improved survival. These effects coincided with a
      decrease in Tfh cells and downstream components. Infiltration of long-lived
      plasma cells into the inflamed kidney was also reduced in the hBM-MSC-treated
      mice. Importantly, hBM-MSCs directly suppressed the in vitro differentiation of
      naive CD4(+) T cells toward Tfh cells in a contact-dependent manner. These
      results suggest that MSCs attenuate lupus nephritis by suppressing the
      development of Tfh cells and the subsequent activation of humoral immune
      components. They thus reveal a novel mechanism by which MSCs regulate humoral
      autoimmune diseases such as SLE.

PMID- 25975933
TI  - Effects of school-based mental health literacy education for secondary school
      students to be delivered by school teachers: A preliminary study.
AB  - AIMS: Improving knowledge and beliefs about mental health (or mental health
      literacy [MHL]) may promote appropriate help-seeking by adolescents who are
      suffering from mental health problems. We developed a concise, school-staff-led
      MHL program and examined its effects. METHODS: The participants comprised 118
      grade-9 students (61 boys and 57 girls). The program consisted of two 50-min
      sessions, and was given by a schoolteacher. The effects of the program were
      evaluated before, immediately after and 3 months after the program, using a self
      report questionnaire. RESULTS: Knowledge of mental health/illnesses and desirable
      behavior for help-seeking were significantly improved immediately after (post
      test, P < 0.001, and P < 0.001, respectively) and 3 months after the program (3
      month follow up, P < 0.001 and P < 0.001, respectively), compared with the test
      before the delivery of the program (pre-test, Wilcoxon signed rank test).
      Proportions of the correct diagnoses of vignette cases of major depression and
      schizophrenia were significantly (P < 0.001) elevated from 38.3% and 19.1% (pre
      test) to 94.7% and 93.6% (post-test), and 91.5% and 86.2% (3-month follow up).
      Intentions to seek help and to provide peers with help with mental health
      problems were also significantly (P < 0.001) elevated at post-test and at 3
      months compared with the pre-test. CONCLUSIONS: A concise, school-staff-led
      program may have a significant effect on the improvement of MHL in secondary
      school students.

PMID- 25975932
TI  - Depression and cognitive impairment following recovery from thrombotic
      thrombocytopenic purpura.
AB  - After recovery from an acute episode of acquired thrombotic thrombocytopenic
      purpura (TTP), patients often describe problems with memory, concentration, and
      endurance. We have previously reported the occurrence of depression and cognitive
      impairment in these patients. In this study, we describe the frequency, severity,
      and clinical course of depression and cognitive impairment. Fifty-two (85%) out
      of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented
      by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for
      depression over 11 years using the Beck Depression Inventory-II; 31 (59%)
      patients screened positive for depression at least once; in 15 (29%), the results
      suggested severe depression at least once. Nine of these 15 patients had a
      psychiatric interview, the definitive diagnostic evaluation; the diagnosis of
      major depressive disorder was established in eight (89%) patients. In 2014,
      cognitive ability was evaluated in 33 patients by the Montreal Cognitive
      Assessment and the Repeatable Battery for Assessment of Neuropsychological Status
      (RBANS). Both tests detected significant cognitive impairment in the patients as
      a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive
      tests in 2006. The 2014 RBANS results were significantly worse than the 2006
      results for the overall score and two out of the five RBANS domains (immediate
      and delayed memory). Neither depression nor cognitive impairment was
      significantly associated with the occurrence of relapses or ADAMTS13 activity
      <10% during remission. These observations emphasize the importance of screening
      evaluations for depression and cognitive impairment after recovery from acquired
      TTP.

PMID- 25975935
TI  - A challenging case of pregnancy with placenta accreta and very rare irregular
      antibodies versus Cromer blood group system: a case report.
AB  - INTRODUCTION: This report describes the challenges of treating a pregnant woman
      who had a rare case of critical placenta accreta with concurrent Cromer system
      anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such
      alloimmunization in a patient with placenta accreta has been reported. CASE
      PRESENTATION: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti
      Kidd A antibodies and placenta accreta was admitted to the obstetric emergency
      department at our university hospital with persistent vaginal bleeding. Her rare
      Cromer blood group system antibodies had been diagnosed 1 month earlier; no
      compatible blood had been found despite a worldwide search. We performed a
      cesarean section after placement of Fogarty balloons in her uterine arteries with
      preoperative endovascular interventional radiology. Other therapeutic
      interventions included preoperative iron administration to raise hemoglobin and
      the scheduled predeposit of autologous blood. Intraoperative therapeutic
      management was aimed at preventing coagulopathy and massive bleeding. With the
      use of alternative medical techniques determined during perioperative planning,
      her intraoperative blood loss was only 1000 mL, despite the placenta accreta. She
      was discharged from the hospital 4 days after cesarean section. CONCLUSIONS: To
      the best of our knowledge, this is the first report of an alloimmunized patient
      with two different alloantibodies and concurrent high risk of bleeding because of
      placenta accreta. The close collaboration among obstetricians, anesthesiologists,
      interventional radiologists, blood bank pathologists and intensive care doctors
      prevented serious consequences in this patient. The exceptional feature of this
      case is the patient's double risk: the placenta accreta and the inability to
      transfuse compatible blood. These two extreme situations challenged the
      multidisciplinary medical team.

PMID- 25975934
TI  - Pharmacokinetics of bound and unbound telaprevir in cirrhotic patients with
      moderate and severe hepatic impairment.
AB  - This study aimed to characterize the pharmacokinetic parameters of telaprevir
      (TVR) in patients with moderate and severe hepatic impairment, measure the
      unbound (pharmacologically active) plasma concentrations of TVR, and determine if
      any changes in TVR exposure were of clinical relevance. Ten patients with
      moderate (Child-Pugh B) hepatic impairment, 10 matched healthy control
      volunteers, and 4 nonmatched patients with severe (Child-Pugh C) hepatic
      impairment received 750 mg TVR every 8 hours for 6 days. Venous blood samples
      were collected at various times throughout the study. Single-dose and steady
      state pharmacokinetics of total and unbound TVR were calculated. Safety and
      tolerability of TVR were also assessed. The mean maximum plasma concentration and
      area under the curve values of total and unbound TVR were lower in patients with
      moderate hepatic impairment compared with matched healthy controls following a
      single dose and at steady state but did not consistently meet statistical
      significance. This trend was also present when patients with severe hepatic
      impairment were compared with the nonmatched healthy controls. However, the
      safety profile of TVR in the patient and healthy volunteer groups was comparable
      with previously published data. These results indicate that reduced plasma
      concentrations of total and unbound TVR in patients with hepatic impairment are
      unlikely to be clinically relevant. 

PMID- 25975936
TI  - Development and validation of an LC-MS/MS method for simultaneous determination
      of piperaquine and 97-63, the active metabolite of CDRI 97-78, in rat plasma and
      its application in interaction study.
AB  - Piperaquine-dihydroartemisinin combination is the latest addition to the
      repertoire of ACTs recommended by the World Health Organization (WHO) for
      treatment of falciparum malaria. Due to the increasing resistance to artemisinin
      derivatives, CSIR-CDRI has developed a prospective short acting, trioxane
      antimalarial derivative, CDRI 97-78. In the present study, a liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)
      method for the simultaneous quantification of piperaquine (PPQ) and 97-63, the
      active metabolite of CDRI 97-78 found in vivo, was developed and validated in 100
      MUL rat plasma using halofantrine as internal standard. PPQ and 97-63 were
      separated using acetonitrile:methanol (50:50, v/v) and ammonium formate buffer
      (10 mM, pH 4.5) in the ratio of 95:5(v/v) as mobile phase under isocratic
      conditions at a flow rate of 0.65 mL/min on Waters Atlantis C18 (4.6 * 50 mm, 5.0
      um) column. The extraction recoveries of PPQ and 97-63 ranged from 90.58 to
      105.48%, while for the internal standard, it was 94.27%. The method was accurate
      and precise in the linearity range 3.9-250 ng/mL for both the analytes, with a
      correlation coefficient (r) of >= 0.998. The intra- and inter-day assay precision
      ranged from 2.91 to 8.45% and; intra- and inter-day assay accuracy was between
      92.50 and 110.20% for both the analytes. The method was successfully applied to
      study the effect of oral co-administration of PPQ on the pharmacokinetics of CDRI
      97-78 in Sprague-dawley rats and vice versa. The co-administration of CDRI 97-78
      caused significant decrease in AUC0-infinity of PPQ from 31.52 +/- 2.68 to 14.84
      +/- 4.33 h*ug/mL. However, co-administration of PPQ did not have any significant
      effect on the pharmacokinetics of CDRI 97-78.

PMID- 25975938
TI  - From specialist to generalist: Developmental transformations in the genetic
      structure of early child abilities.
AB  - The heritability of abilities increases substantially over development, and much
      of heritable variation in abilities is shared with other abilities. No study,
      however, has formally tested the extent to which developmental increases in
      heritability occur on shared versus unique variation in child abilities. A
      transactional perspective predicts that the relative proportion of shared to
      total genetic variance will increase with age, whereas an endogenous perspective
      predicts that such proportion will be invariant with age. We tested these
      competing predictions using data from a sample of 292 twins providing a total of
      578 cross-sectional and longitudinal observations between ages 0 and 6 years on
      measures of Communication, Gross Motor, Fine Motor, Problem-Solving, and Personal
      Social abilities. Consistent with predictions of the transactional perspective,
      developmental increases in heritability were localized to variance shared across
      abilities.

PMID- 25975937
TI  - Morphological Characterisation of Unstained and Intact Tissue Micro-architecture
      by X-ray Computed Micro- and Nano-Tomography.
AB  - Characterisation and quantification of tissue structures is limited by sectioning
      induced artefacts and by the difficulties of visualising and segmenting 3D
      volumes. Here we demonstrate that, even in the absence of X-ray contrast agents,
      X-ray computed microtomography (microCT) and nanotomography (nanoCT) can
      circumvent these problems by rapidly resolving compositionally discrete 3D tissue
      regions (such as the collagen-rich adventitia and elastin-rich lamellae in intact
      rat arteries) which in turn can be segmented due to their different X-ray
      opacities and morphologies. We then establish, using X-ray tomograms of both
      unpressurised and pressurised arteries that intra-luminal pressure not only
      increases lumen cross-sectional area and straightens medial elastic lamellae but
      also induces profound remodelling of the adventitial layer. Finally we apply
      microCT to another human organ (skin) to visualise the cell-rich epidermis and
      extracellular matrix-rich dermis and to show that conventional histological and
      immunohistochemical staining protocols are compatible with prior X-ray exposure.
      As a consequence we suggest that microCT could be combined with optical
      microscopy to characterise the 3D structure and composition of archival paraffin
      embedded biological materials and of mechanically stressed dynamic tissues such
      as the heart, lungs and tendons. 

PMID- 25975939
TI  - Minimally Invasive Port Access Approach for Reoperations on the Mitral Valve.
AB  - BACKGROUND: In patients requiring a second-time or more operation on the mitral
      valve (MV), we assessed whether the outcomes of the minimally invasive port
      access approach (port access group) were equivalent to those of the traditional
      redo sternotomy approach (redo sternotomy group). METHODS: In a retrospective
      review (1998-2011), 409 patients had previous MV operations requiring a second
      time or more MV reintervention. Of those, 67 patients had the port access
      approach, and 342 had the redo sternotomy approach. Of the latter, 220 met the
      inclusion criteria because emergencies, patients with endocarditis, and those
      requiring concomitant procedures involving aortic valve and aorta were excluded.
      RESULTS: New York Heart Association class 2 or above, age, atrial fibrillation,
      and surgical indications were similar in both groups. The port access group had
      more patients with previous MV repair (78% [n = 52] vs 41% [n = 90], p < 0.01)
      than with MV replacement (19% [n = 13) vs 53% [n = 116], p < 0.01). Concomitant
      procedures were similar (20% [n = 14] vs 27% [n = 59], p = 0.4). The MV re-repair
      rates were similar (19% [n = 10] vs 22% [n = 20], p = 1). The cardiopulmonary
      bypass times (153 +/- 42 minutes vs 172 +/- 83 minutes, p = 0.07) and aortic
      cross-clamping times (104 +/- 38 minutes versus 130 +/- 71 minutes, p < 0.01)
      were lower in the port access group. Mortality was lower in the port access
      group, although not significantly (3.0% [n = 2] vs 6.0% [n = 13], p = 0.5). The
      rates of postoperative stroke were similar (3.0% [n = 2] vs 3.2% [n = 7], p = 1).
      On postoperative echocardiography, freedom from mitral regurgitation >2+ was 100%
      in the port access group and 99% in the redo sternotomy group. The mean hospital
      length of stay was 11 +/- 15 days versus 14 +/- 12 days (p = 0.07). CONCLUSIONS:
      The port access approach can be safely adopted for reoperations on the MV without
      compromising postoperative mortality or MV function.

PMID- 25975940
TI  - Identifying Abnormal Ostial Morphology in Anomalous Aortic Origin of a Coronary
      Artery.
AB  - BACKGROUND: Anomalous origin of a coronary artery from the contralateral sinus of
      Valsalva is associated with exercise-induced ischemia and sudden death. That is
      thought to be due to aortic enlargement in patients with an elliptical ostium. We
      hypothesize that virtual angioscopy can identify abnormal coronary ostial
      morphology in these patients. METHODS: We retrospectively analyzed 55 consecutive
      pediatric coronary artery magnetic resonance imaging studies from January 2006 to
      January 2010 with the diagnosis of anomalous right (n = 20), or left (n = 7)
      coronary artery, or normal coronary origins (n = 28). One postmortem heart
      specimen with anomalous left coronary artery was imaged and analyzed to validate
      our technique. Virtual angioscopy analysis was used for visualization and
      measurement of the coronary ostia. RESULTS: Distinct aortic origins of the right
      and left coronaries were seen in all 55 studies. An elliptical orifice with a
      longer superior-inferior dimension was seen in all anomalous ostia, in contrast
      to a circular ostium in all normal origins. That was quantified in anomalous
      ostia with a long-axis to short-axis ratio of 2.5 +/- 0.5 (right) and 2.4 +/- 0.5
      (left) compared with 1.1 +/- 0.2 (right) and 1.0 +/- 0.3 (left) in controls (p <
      0.001 for right and left ostia comparisons). Ostial morphology was confirmed in
      all 9 patients who underwent operative repair and in 1 patient at autopsy.
      CONCLUSIONS: Virtual angioscopy identifies abnormal ostial morphology in
      anomalous coronary artery patients, which is important for characterizing the
      diagnosis of patients who may be at risk for sudden death.

PMID- 25975941
TI  - The Influence of Mitral Annuloplasty on Left Ventricular Flow Dynamics.
AB  - BACKGROUND: Mitral valve (MV) repair using annuloplasty rings is the preferred
      method of treatment for MV regurgitation, but the impact of annuloplasty ring
      placement on left ventricular intraventricular flow has not been studied.
      METHODS: Annuloplasty rings of varying sizes were placed in 5 healthy sheep
      (intercommissural ring sizes were 24, 26, 28, 30, and 32 mm), and three
      dimensional phase contrast magnetic resonance imaging (4D flow MRI) was performed
      before and 1 week after ring placement. RESULTS: Normal diastolic flow consisted
      of diastolic intraventricular vortices that naturally unwound during systole.
      Postsurgical intraventricular flow was highly disturbed in all sheep, and the
      disturbance was greatest for undersized rings. Ring size was highly correlated
      with the diastolic inflow angle (Pearson's r = -0.62, p < 0.1, 95% confidence
      interval: -0.92 to 0.14). There was a mean angle increase of mean diastolic
      inflow angle increase of 12.3 degrees (< 30 mm, p < 0.01, 95% confidence
      interval: 4.8 to 19.6) for rings less than 30 mm. There was an inverse
      relationship between peak velocity and annuloplasty ring area (Pearson's r = 
      0.80, p < 0.05, 95% confidence interval: -0.96 to -0.2). Transmitral pressure
      gradients increased significantly from baseline 0.73 +/- 0.18 mm Hg to after
      annuloplasty 2.31 +/- 1.04 mm Hg (p < 0.05). CONCLUSIONS: Mitral valve
      annuloplasty ring placement disturbs normal left ventricular intraventricular
      flow patterns, and the degree of disturbance is closely associated with
      annuloplasty ring size.

PMID- 25975942
TI  - Predictors of Survival and Modes of Failure After Mitroflow Aortic Valve
      Replacement in 1,003 Adults.
AB  - BACKGROUND: Midterm outcomes are unknown for patients undergoing aortic valve
      replacement (AVR) with a Mitroflow bovine pericardial prosthesis (Sorin Group,
      Inc) and without anticalcification treatment. Recent reports warn of early
      senescence in younger adults. METHODS: From January 2004 through December 2011,
      1,003 adults underwent Mitroflow AVR. The mean follow-up time was 25.0 (standard
      deviation [20.6]) months (total, 2,060 patient-years; maximum, 9 years). The
      patients were stratified for analysis according to age at implantation: group A,
      <60 years (n = 63, 6.3%); group B, 60-69 years (n = 173, 17.2%); group C, 70-79
      years (n = 432, 43.1%); and group D, 80 years or older (n = 335, 33.4%). RESULTS:
      The mean age was 74.8 years (SD 9.8), and 609 patients (60.7%) were men. Aortic
      valve stenosis was present in 912 patients (90.9%), and 113 (11.3%) had severe
      aortic regurgitation. There were 27 (2.7%) early deaths, 15 of 431 (3.5%)
      underwent concomitant coronary artery bypass grafting while 12 of 572 (2.1%) did
      not (p = 0.18), and 151 patients (15.1%) died during follow-up. Nineteen AVRs
      (1.9%) required re-replacement through August 2013; 12 (63.2%) were associated
      with structural valve deterioration. The overall rates of freedom from valve
      related reoperation at 3 and 5 years were 98.3% and 93.8%, respectively. Group A
      had the greatest number of reoperations (6/63; p < 0.001). The overall survival
      rates at 1 and 5 years were 91.2% and 67.3%, respectively. Independent predictors
      of mortality were poorer New York Heart Association functional class (hazard
      ratio [HR], 2.1; p < 0.001), atrial fibrillation (HR, 1.8; p = 0.002), and prior
      cardiac operation (HR, 1.8; p = 0.003). CONCLUSIONS: Midterm follow-up shows
      acceptable hemodynamic performance of the Mitroflow biologic aortic valve
      prosthesis in selected patients 60 years old and older. Ongoing follow-up will be
      necessary to understand long-term performance and outcomes.

PMID- 25975943
TI  - The Association of Low Social Support with Breast Milk Expression in Low-Income
      Mother-Preterm Infant Dyads.
AB  - BACKGROUND: Premature infants benefit from receiving expressed breast milk (BM),
      but expressing breast milk is difficult for new mothers. Little is known about
      mothers' social support and BM expression during the premature infant's hospital
      stay. OBJECTIVE: We examined whether low maternal social support was associated
      with breast milk expression initiation and low breast milk expression among low
      income mothers of premature infants. METHODS: Maternal intake interview data and
      daily infant data on proportion of nutrition from BM during hospitalization were
      analyzed from a larger randomized trial testing a developmental intervention on
      181 mother-premature infant dyads with at least 2 of 10 social-environmental
      risks. Multivariable modified Poisson regression was used to examine the
      relationship between social support (Personal Resources Questionnaire 2000;
      dichotomized as low for lowest quartile), initiation (any breast milk expressed
      vs none), and low breast milk expression (if BM was < 30% of infant total
      milk/formula intake during hospitalization). RESULTS: Breast milk expression was
      initiated by 70.2% of mothers, and 32.3% of those mothers had low breast milk
      expression. In adjusted multivariable analyses, social support did not relate to
      the initiation of breast milk expression but was significantly associated with
      low breast milk expression among mothers who initiated (adjusted relative risk =
      1.57; 95% confidence interval, 1.00-2.47). CONCLUSION: Low social support was not
      associated with initiation but was associated with low breast milk expression
      during hospitalization. Interventions to enhance social support for mothers of
      premature infants, especially those reporting low social support from family and
      friends, may increase in-hospital expression and long-term breastfeeding.

PMID- 25975944
TI  - Serious and potentially life threatening complications of cardiac stress testing:
      Physiological mechanisms and management strategies.

PMID- 25975945
TI  - "Reverse Redistribution" Pattern on SPECT Myocardial Perfusion Imaging from
      Endothelial Dysfunction at Rest and from Subendocardial Ischemia.

PMID- 25975946
TI  - Impact of medications on mIBG uptake, with specific attention to the heart:
      Comprehensive review of the literature.
AB  - BACKGROUND: A critical review of the literature on drug interactions with mIBG
      uptake was performed to allow formulation of contemporary guidance regarding
      withholding medications prior to clinical imaging studies. METHODS: Published
      information was extracted on the experimental system used, the quantitative
      characteristics of the measurements, and whether any data directly examining
      cardiac tissues were included. Level of evidence for each medication category was
      assessed on a qualitative scale of very low, low, medium, or high. Strength of
      medication effect for inhibition of mIBG uptake was judged as none, weak,
      moderate, or strong. RESULTS: The only medications for which level of evidence
      was judged high were labetalol and reserpine. Level of evidence was judged medium
      for tricyclic antidepressants, calcium channel blockers, and antiarrhythmics
      (specifically amiodarone). Evidence was judged sufficient to recommend
      withholding labetalol and the tricyclic antidepressants prior to mIBG cardiac
      imaging. Mechanistic evidence was sufficient to suggest consideration of
      withdrawal of sympathomimetic amines and serotonin-norepinephrine reuptake
      inhibitors (SNRIs). CONCLUSIONS: As there is strong evidence for inhibition of
      mIBG uptake in only a small number of compounds, clinical decisions regarding
      withdrawal of concomitant medications should be individualized by considering the
      potential consequences of a false-positive (artificially low cardiac uptake)
      imaging result.

PMID- 25975948
TI  - Correlation of Arsenic Levels in Smokeless Tobacco Products and Biological
      Samples of Oral Cancer Patients and Control Consumers.
AB  - It has been extensively reported that chewing of smokeless tobacco (SLT) can lead
      to cancers of oral cavity. In present study, the relationship between arsenic
      (As) exposure via chewing/inhaling different SLT products in oral cancer patients
      have or/not consumed SLT products was studied. The As in different types of SLT
      products (gutkha, mainpuri, and snuff) and biological (scalp hair and blood)
      samples of different types of oral cancer patients and controls were analyzed.
      Both controls and oral cancer patients have same age group (ranged 30-60 years),
      socio-economic status, localities, and dietary habits. The concentrations of As
      in SLT products and biological samples were measured by electrothermal atomic
      absorption spectrophotometer after microwave-assisted acid digestion. The
      validity and accuracy of the methodology were checked by certified reference
      materials. The resulted data of present study indicates that the concentration of
      As was significantly higher in scalp hair and blood samples of oral cancer
      patients than those of controls (p<0.001). It was also observed that the values
      of As were two- to threefolds higher in biological samples of controls subjects,
      consuming SLT products as compared to those have none of these habits (p>0.01).
      The intake of As via consuming different SLT may have synergistic effects, in
      addition to other risk factors associated with oral cancer.

PMID- 25975949
TI  - Conference Summary and Recent Advances: the 8th Conference on Metal Toxicity and
      Carcinogenesis.

PMID- 25975950
TI  - Author's reply to Langford, Cowen, Chekroud and Krystal.

PMID- 25975951
TI  - BAFF promotes proliferation of human mesangial cells through interaction with
      BAFF-R.
AB  - BACKGROUND: B cell activating factor belonging to the TNF family (BAFF) is vital
      for B cell survival, proliferation and activation. Evidence indicates that BAFF
      is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis,
      IgA nephropathy). However, the effect of BAFF on human mesangial cells is not
      known. METHODS: The impact of BAFF on the proliferation of a human mesangial cell
      line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and
      downstream signal transduction were explored. The influence of BAFF on the
      expression of related genes was also studied. RESULTS: Our data indicated that
      BAFF had a proliferative effect on human mesangial cells, as supported by the
      results of cell proliferation assays and the inhibited expression of the pro
      apoptotic gene Bim. BAFF-R was expressed on the cell membrane of human mesangial
      cells and blockade of BAFF/BAFF-R binding abrogated the proliferative effect of
      BAFF on human mesangial cells. BAFF stimulation led to rapid phosphorylation of
      NF-kappaBp65, Akt and MAPK p38 kinase in human mesangial cells, whereas it had no
      effect on the expression of NF-kappaB p100 and phosphorylation of Erk. The
      phosphorylation of Akt was very sensitive to blockade of BAFF/BAFF-R ligation,
      although activation of MAPK p38 and NF-kappaBp65 was not. BAFF treatment resulted
      in decreased expression of BAFF-R, which implied negative feedback regulation
      after its binding. CONCLUSIONS: BAFF promoted proliferation of human mesangial
      cells, which was mediated via BAFF-R. The BAFF/BAFF-R interaction triggered Akt,
      p65 and p38 activation, with Akt phosphorylation being tightly dependent on
      BAFF/BAFF-R interaction.

PMID- 25975953
TI  - Letter to the Editor Re: Bundred et al. "Comparison of multi-frequency
      bioimpedance with perometry for the early detection and intervention of
      lymphoedema after axillary node clearance for breast cancer".

PMID- 25975952
TI  - Combined inhibition of glycolysis and AMPK induces synergistic breast cancer cell
      killing.
AB  - Targeting glycolysis for cancer treatment has been investigated as a therapeutic
      method but has not offered a feasible chemotherapeutic strategy. Our aim was to
      examine whether AMP-activated protein kinase (AMPK), a conditional oncogene,
      rescues the energetic stress and cytotoxicity induced by 2-deoxyglucose (2-DG), a
      glycolytic inhibitor, and the related mechanisms. Luciferin/luciferase adenosine
      triphosphate (ATP) determination, Western analysis, qRT-PCR analyses, MTT growth
      assay, clonogenic assay, and statistical analysis were performed in this study. 2
      DG decreased ATP levels and subsequently activated AMPK, which contribute to
      intracellular ATP recovery in MCF-7 cells thus exhibiting no apparent
      cytotoxicity. Compound C, an AMPK inhibitor, further potentiates 2-DG-induced
      decrease in ATP levels and inhibits their recovery. 2-DG, via AMPK activation,
      stimulated cAMP response element-binding protein (CREB) phosphorylation and
      activity and promoted nuclear peroxisome proliferator-activated receptor gamma
      coactivator-1-beta (PGC-1beta) and estrogen-related receptor alpha (ERRalpha)
      protein expression, leading to augmented mitochondrial biogenesis and expression
      of fatty acid oxidation (FAO) genes including PPARalpha, MCAD, CPT1C, and ACO.
      This metabolic adaptation elicited by AMPK counteracts the ATP-depleting and
      cancer cell-killing effect of 2-DG. However, 2-DG in combination with AMPK
      antagonists or small interfering RNA caused a dramatic increase in cytotoxicity
      in MCF-7 but not in MCF-10A cells. Similarly, when combined with inhibition of
      CREB/PGC-1beta/ERRalpha pathway, 2-DG saliently suppressed mitochondrial
      biogenesis and the expression of FAO genes, depleted ATP production, and enhanced
      cytotoxicity in cancer cells. Collectively, the combination of 2-DG and AMPK
      inhibition synergistically enhanced the cytotoxic potential in breast cancer
      cells with a relative nontoxicity to normal cells and may offer a promising,
      safe, and effective breast cancer therapeutic strategy. 

PMID- 25975954
TI  - Digoxin use after diagnosis of breast cancer and survival: a population-based
      cohort study.
AB  - Digoxin has been shown to have an estrogenic effect and is associated with
      increased risk of gynecomastia and estrogen-sensitive cancers such as breast and
      uterus cancer. These findings, particularly recent observations of increased
      breast cancer risk, raise questions about the safety of digoxin use in breast
      cancer patients. Therefore, we investigated whether digoxin use after breast
      cancer diagnosis increased the risk of breast cancer-specific mortality in breast
      cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from
      1998 to 2009 was identified from English cancer registries (from the National
      Cancer Data Repository). This cohort was linked to the UK Clinical Practice
      Research Datalink (to provide digoxin and other prescription records) and to the
      Office of National Statistics mortality data (to identify breast cancer-specific
      deaths). Using time-dependent Cox regression models, unadjusted and adjusted
      hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the
      association between post-diagnostic exposure to digoxin and breast cancer
      specific and all-cause mortality. In 17,842 breast cancer patients, there were
      2219 breast cancer-specific deaths. Digoxin users appeared to have increased
      breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39
      2.15) but this association was entirely attenuated after adjustment for potential
      confounders (adjusted HR 0.91; 95 % CI 0.72-1.14). In this large population-based
      breast cancer cohort study, there was little evidence of an increase in breast
      cancer-specific mortality with digoxin use after diagnosis. These results provide
      some reassurance that digoxin use is safe in breast cancer patients. 

PMID- 25975955
TI  - Second primary breast cancer in BRCA1 and BRCA2 mutation carriers: 10-year
      cumulative incidence in the Breast Cancer Family Registry.
AB  - BReast CAncer genes 1 and 2 (BRCA1 and BRCA2) mutation carriers diagnosed with
      breast cancer are at increased risk of developing a second primary breast cancer.
      Data from high-risk clinics may be subject to different biases which can cause
      both over and underestimation of this risk. Using data from a large multi
      institutional family registry we estimated the 10-year cumulative risk of second
      primary breast cancer including more complete testing information on family
      members. We prospectively followed 800 women diagnosed with breast cancer from
      the Breast Cancer Family Registry (BCFR) who were carriers of a BRCA1 or BRCA2
      pathogenic mutation or a variant of unknown clinical significance. In order to
      limit survival and ascertainment bias, cases were limited to those diagnosed with
      a first primary breast cancer from 1994 to 2001 and enrolled in the BCFR within 3
      years after their cancer diagnosis. We excluded women enrolled after being
      diagnosed with a second breast cancer. We calculated 10-year incidence of second
      primary breast cancers. The 10-year incidence of a second primary breast cancer
      was highest in BRCA1 mutation carriers (17 %; 95 % CI 11-25 %), with even higher
      estimates in those first diagnosed under the age of 40 (21 %; 95 % CI 13-34 %).
      Lower rates were found in BRCA2 mutation carriers (7 %; 95 % CI 3-15 %) and women
      with a variant of unknown clinical significance (6 %; 95 % CI 4-9 %). Whereas the
      cumulative 10-year incidence of second primary breast cancer is high in BRCA1
      mutation carriers, the estimates in BRCA2 mutation carriers and women with
      variants of unknown clinical significance are similar to those reported in women
      with sporadic breast cancer. 

PMID- 25975956
TI  - Relevance of betaGal-betaGalNAc-containing glycans and the enzymes involved in
      their synthesis for invasion and survival in breast cancer patients.
AB  - To study the influence of glycosylation on breast cancer progression by analyses
      on glycan, mRNA, and protein level. For detection of glycan structures, we
      performed lectin histochemistry with five lectins of different specificity (UEA
      1, HPA, GNA, PNA, and PHA-L) on a tissue microarray with >400 breast cancer
      samples. For comparison, mRNA expression of glycosylation enzymes involved in the
      synthesis of HPA and PNA binding glycostructures (GALNT family members and
      C1GALT1) was analyzed in microarray data of 194 carcinomas. Additionally, C1GALT1
      protein expression was analyzed by Western blot analysis in 106 tumors.
      Correlations with clinical and histological parameters including recurrence-free
      (RFS) and overall survival (OAS) were calculated. Positive binding of four
      lectins (HPA, GNA, PNA, and PHA-L) correlated significantly with parameters
      involved in tumor metastasis, namely lymphangiosis, vascular invasion, lymph node
      involvement, and presence of disseminated tumor cells in bone marrow. HPA and PNA
      binding also showed a negative prognostic impact in our cohort. Correspondingly,
      high expression of C1GALT1, GALNT1, GALNT8, or GALNT14 mRNA and C1GALT1 protein
      correlated significantly with shorter OAS. Notably, combined overexpression of
      C1GALT1/GALNT1 or C1GALT1/GALNT8 mRNA was associated with a significantly reduced
      OAS (HR 3.15 and 2.73) and RFS (HR 2.01 and 1.94), pointing to an additive
      influence of these enzymes. This prognostic impact retained significance in
      multivariate analysis including classical prognostic markers. Our data indicate
      that glycan structures containing betaGal-betaGalNAc residues and the enzymes
      involved in their synthesis play a role in breast cancer progression, at least
      partly by their promoting influence on haematogenic and lymphatic spread. 

PMID- 25975957
TI  - Drug repositioning and repurposing: terminology and definitions in literature.
AB  - Drug repositioning and similar terms have been a trending topic in literature and
      represent novel drug development strategies. We analysed in a quantitative and
      qualitative manner how these terms were used and defined in the literature. In
      total, 217 articles referred to 'drug repositioning', 'drug repurposing', 'drug
      reprofiling', 'drug redirecting' and/or 'drug rediscovery'. Only 67 included a
      definition ranging from brief and general to extensive and specific. No common
      definition was identified. Nevertheless, four common features were found:
      concept, action, use and product. The different wording used for these features
      often leads to essential differences in meaning between definitions. In case a
      clear definition is needed, for example from a legal or regulatory perspective,
      the features can provide further guidance. 

PMID- 25975958
TI  - A Systematic Review of Data Collection Techniques Used to Measure Preschool
      Children's Knowledge of Food and Nutrition.
AB  - OBJECTIVE: To identify and review data collection techniques used to measure
      preschool children's knowledge of food and nutrition. DESIGN: A systematic review
      of published research guided by the Preferred Reported Items for Systematic
      Reviews and Meta-analyses statement. PARTICIPANTS: Published journal articles
      between 1980 and 2013 reporting research involving the measurement of preschool
      children's (aged 3-5 years) knowledge of food and nutrition. RESULTS: Twenty
      studies were eligible for inclusion. The studies reported the use of a range of
      innovative age-appropriate techniques to assess children's knowledge of food and
      nutrition. Data collection techniques were grouped under 3 broad approaches: (1)
      interviews, (2) use of stimulus material and prompts, and (3) structured play
      based activities. Only 3 of the reviewed studies tested for both reliability
      (test-retest and internal consistency) and face and content validity. Only 9 of
      the reviewed studies reported pilot-testing their instruments before use.
      CONCLUSIONS AND IMPLICATIONS: Results from this review suggest that additional
      research is needed to develop more valid and reliable measures to assess
      preschool children's knowledge of food and nutrition. Assessment tools need to be
      pilot-tested, refined, and adapted to suit both the specific audience and the
      components of the nutrition knowledge being targeted by an intervention before
      implementing a nutrition education program.

PMID- 25975959
TI  - Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive
      activity in murine vibrissal dermal papilla in vitro.
AB  - BACKGROUND: The dermal papilla is composed of a small clump of mesenchymal cells,
      called dermal papilla cells (DPCs). DPCs closely interact with epidermal cells to
      give rise to hair follicles and shafts during hair follicle development and the
      hair cycle. DPCs are promising cell sources for hair regeneration therapy for
      alopecia patients. However, once DPCs are put into conventional two-dimensional
      culture conditions, they quickly lose their capability to produce hair follicles.
      OBJECTIVE: We aimed to expand a sufficiently large population of DPCs that retain
      their hair inductive activity. METHODS: Murine DPCs were cultured in the presence
      of platelet-derived growth factor-AA (PDGF-AA) and fibroblast growth factor 2
      (FGF2). Expressions of follicular-related genes were analyzed by real time PCR
      and hair inductive activity was determined by patch assay and chamber assay in
      vivo. RESULTS: FGF2 significantly increased the expression of platelet-derived
      growth factor receptor alpha (PDGFRalpha) in cultured vibrissal DPCs. PDGF-AA, a
      ligand of PDGFRalpha, promoted proliferation of DPCs synergistically when
      utilized with FGF2 and enhanced the expression of several follicular-related
      genes in DPCs. Hair reconstitution assays revealed that DPCs treated with both
      PDGF-AA and FGF-2 were able to maintain their hair inductive activity better than
      those treated with FGF2 alone. CONCLUSION: Both cell proliferation and hair
      inductive activity in murine DPCs are maintained by the synergistic effect of
      FGF2 and PDGF-AA.

PMID- 25975960
TI  - Endocannabinoid and ceramide levels are altered in patients with colorectal
      cancer.
AB  - Endocannabinoids and ceramides have demonstrated growth inhibition, cell death
      induction and pro-apoptotic activity in cancer research. In the present study, we
      describe the profiles of two major endocannabinoids, ceramides, free fatty acids
      and relevant metabolic enzymes in 47 pairs of human colorectal cancer tissues and
      adjacent non-tumor tissues. Among them, anandamide (AEA) and its metabolite,
      arachidonic acid (AA), were markedly upregulated in cancer tissues particularly
      in those with lymphatic metastasis. The levels of C16 and C24 ceramides were
      significantly elevated in the colorectal tumor tissues, while levels of C18 and
      C20 ceramides showed opposite trends. Levels of two enzymes participating in the
      biosynthesis and degradation of AEA, N-acyl-phosphatidylethanolamine-hydrolyzing
      phospholipase D (NPLD) and fatty acid amide hydrolase (FAAH), together with the
      most abundant ceramide synthases (CerS1, CerS2, CerS5 and CerS6) in the colon
      were also determined. Quantitative-PCR analysis indicated that the mRNA levels of
      these enzymes were overexpressed in the tumor tissues. The activities of NPLD and
      FAAH were also upregulated. In addition, both gene and protein expression levels
      of cannabinoid receptor 1 (CB1) were elevated but not of CB2. Elevation of AEA
      and alteration of ceramides (C16, C24, C18, C20) may qualify as potential
      endogenous biomarkers and novel drug targets for colorectal cancer.

PMID- 25975961
TI  - Downstream clinical consequences of stress cardiovascular magnetic resonance
      based on appropriate use criteria.
AB  - BACKGROUND: Appropriate use criteria (AUC) have been developed by professional
      organizations as a response to the rising costs of imaging, with the goal of
      optimizing test-patient selection. Consequently, the AUC are now increasingly
      used by third-party-payers to assess reimbursement. However, these criteria were
      created by expert consensus and have not been systematically assessed for CMR.
      The aim of this study was to determine the rates of abnormal stress-CMR and
      subsequent downstream utilization of angiography and revascularization procedures
      based on the most recent AUC. METHODS: 300 consecutive patients referred for CMR
      stress testing were prospectively enrolled. Two cardiologists reviewed all
      clinical information before the CMR-stress test and classified the test as
      "appropriate', "maybe appropriate" or "rarely appropriate" according to the 2013
      AUC. Patients were followed for 2 months for the primary outcomes of coronary
      angiography and/or revascularization. RESULTS: 49.7% of stress CMRs were
      appropriate, 36.7% maybe appropriate, and 13.6% rarely appropriate. Ischemia was
      significantly more likely to be seen in the appropriate (18.8%) or maybe
      appropriate groups (21.8%) than the rarely appropriate group (4.8%) (p = 0.030
      and p = 0.014 respectively). Referral for cardiac catheterization was not
      significantly different in the appropriate (10.1%) and maybe appropriate groups
      (10.0%) compared to the rarely appropriate group (2.4%) (p = 0.119 and p = 0.127
      respectively). No patients undergoing catheterization in the rarely appropriate
      group went on to require revascularization, in contrast to 53.3% of the
      appropriate vs 36.4% of the maybe appropriate patients (p = 0.391). Presence of
      ischemia led to referral for cardiac catheterization in 50.0% of the appropriate
      group vs 33.3% of the maybe appropriate group (p = 0.225); in contrast to none of
      the rarely appropriate group. CONCLUSIONS: The great majority of tests were
      classified as appropriate or maybe appropriate. Downstream cardiac
      catheterization rates were similar in all 3 groups. However, rarely appropriate
      studies never required revascularization, suggesting suboptimal resource
      utilization. Studies classified as maybe appropriate had similar rates of
      abnormal findings and led to similar rates of downstream catheterization and
      revascularization as those that were deemed appropriate. This suggests that
      consideration could be given to upgrading some of the common maybe appropriate
      indications to the appropriate category.

PMID- 25975962
TI  - Atomistic design of microbial opsin-based blue-shifted optogenetics tools.
AB  - Microbial opsins with a bound chromophore function as photosensitive ion
      transporters and have been employed in optogenetics for the optical control of
      neuronal activity. Molecular engineering has been utilized to create colour
      variants for the functional augmentation of optogenetics tools, but was limited
      by the complexity of the protein-chromophore interactions. Here we report the
      development of blue-shifted colour variants by rational design at atomic
      resolution, achieved through accurate hybrid molecular simulations,
      electrophysiology and X-ray crystallography. The molecular simulation models and
      the crystal structure reveal the precisely designed conformational changes of the
      chromophore induced by combinatory mutations that shrink its pi-conjugated system
      which, together with electrostatic tuning, produce large blue shifts of the
      absorption spectra by maximally 100 nm, while maintaining photosensitive ion
      transport activities. The design principle we elaborate is applicable to other
      microbial opsins, and clarifies the underlying molecular mechanism of the blue
      shifted action spectra of microbial opsins recently isolated from natural
      sources.

PMID- 25975963
TI  - Characteristics and Outcomes of Granulomatosis With Polyangiitis (Wegener) and
      Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the
      European Renal Association-European Dialysis and Transplant Association Registry.
AB  - BACKGROUND: This study describes the incidence and outcomes of European patients
      requiring renal replacement therapy (RRT) for kidney failure due to
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). STUDY
      DESIGN: Cohort study. SETTING & PARTICIPANTS: 12 renal registries providing
      individual RRT patient data to the European Renal Association-European Dialysis
      and Transplant Association (ERA-EDTA) Registry in 1993-2012 participated.
      PREDICTOR: Cause of primary kidney disease: AAV (ie, granulomatosis with
      polyangiitis [Wegener] and microscopic polyangiitis) versus 3 separate matched
      control groups without AAV: (1) primary glomerulonephritis, (2) diabetes
      mellitus, and (3) disease other than diabetes mellitus as the cause of primary
      kidney disease, including glomerulonephritis (termed "nondiabetes"). OUTCOMES:
      Incidence, causes of death, and survival. MEASUREMENTS: ERA-EDTA primary renal
      disease codes. RESULTS: 2,511 patients with AAV (1,755, granulomatosis with
      polyangiitis; 756, microscopic polyangiitis) were identified, representing an
      incidence of 1.05 per million population (pmp) for granulomatosis with
      polyangiitis (predominating in Northern Europe) and 0.45 pmp for microscopic
      polyangiitis (prevailing in Southern Europe). Kidney transplantation was
      performed in 558 (22.2%) patients with vasculitis. The 10-year probability for
      survival on RRT after day 91 was 32.5% (95% CI, 29.9%-35.1%) in patients with
      vasculitis. Survival on RRT after day 91 did not differ between AAV and matched
      nondiabetes patients. Patient and transplant survival after kidney
      transplantation, adjusted for time period and country, was better in AAV than in
      matched nondiabetes patients (HRs of 0.81 [95% CI, 0.67-0.99] and 0.82 [95% CI,
      0.69-0.96], respectively). LIMITATIONS: No data for extrarenal manifestations,
      treatment, and relapses. CONCLUSIONS: Geographical differences in the incidence
      of RRT for kidney failure due to granulomatosis with polyangiitis and microscopic
      polyangiitis copied their distribution in the general population. Overall
      survival on RRT after day 91 for patients with AAV was similar to that for
      patients with nondiabetes diagnoses. Our results suggest that patients with AAV
      are suitable candidates for kidney transplantation with favorable survival
      outcomes.

PMID- 25975965
TI  - Hemodialysis Arteriovenous Vascular Access Creation After Kidney Transplant
      Failure.
AB  - BACKGROUND: Little is known about vascular access in patients starting
      hemodialysis therapy after kidney transplant failure. STUDY DESIGN: Retrospective
      cohort study. SETTING & PARTICIPANTS: Adult patients (aged >=18 years) who
      started hemodialysis therapy in Ontario, Canada, from January 1, 2001, through
      December 31, 2010, after kidney transplant failure. PREDICTOR: Patient clinical
      and demographic characteristics. OUTCOMES: Proportion and timing of arteriovenous
      (AV) vascular access creation (fistula or graft) 12 months prior and up to 24
      months after starting hemodialysis therapy. MEASUREMENTS: Event rates and outcome
      predictors. RESULTS: Our cohort included 683 patients with a mean age of 48 years
      and >50% with comorbidity index score < 3. In the 12 months predialysis and 24
      months postdialysis, 16% and 47% of patients had an AV access created,
      respectively. In the postdialysis period, 13%, 26%, and 38% of patients had an AV
      access creation at 3, 6, and 12 months, respectively. History of coronary artery
      disease, diabetes mellitus, and peritoneal dialysis use prior to transplantation
      were associated with a lower likelihood of AV access creation. LIMITATIONS:
      Residual selection bias from unmeasured variables beyond the data elements.
      CONCLUSIONS: In Ontario, AV access creation, both before and after starting
      hemodialysis therapy, is low in patients with kidney transplant failure despite
      their being younger and healthier compared to the overall hemodialysis
      population. This highlights the need for a predialysis care pathway in the
      transplantation clinic and an active strategy to identify this patient cohort
      receiving hemodialysis to align modality and access choices.

PMID- 25975964
TI  - A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes
      Mellitus, and Hypertension With Acute Kidney Injury.
AB  - BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney
      injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine
      albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and
      absence of these conditions is uncertain. STUDY DESIGN: Meta-analysis of cohort
      studies. SETTING & POPULATION: 8 general-population (1,285,045 participants) and
      5 chronic kidney disease (CKD; 79,519 participants) cohorts. SELECTION CRITERIA
      FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium. PREDICTORS:
      Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration
      creatinine equation, urine ACR, and interactions. OUTCOME: Hospitalization with
      AKI, using Cox proportional hazards models to estimate HRs of AKI and random
      effects meta-analysis to pool results. RESULTS: During a mean follow-up of 4
      years, there were 16,480 episodes of AKI in the general-population and 2,087
      episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher
      risks of AKI in individuals with or without diabetes and with or without
      hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in
      nondiabetic patients, HRs for AKI were generally higher in diabetic patients at
      any level of eGFR. The same was true for diabetic patients at all levels of ACR
      compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs
      was greater in those without diabetes than with diabetes, but similar with higher
      ACRs in those without versus with diabetes. Those with hypertension had a higher
      risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However,
      risk gradients for AKI with both lower eGFRs and higher ACRs were greater for
      those without than with hypertension. LIMITATIONS: AKI identified by diagnostic
      code. CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks
      of AKI among individuals with or without either diabetes or hypertension.

PMID- 25975966
TI  - Association of Predialysis Calculated Plasma Osmolarity With Intradialytic Blood
      Pressure Decline.
AB  - BACKGROUND: The rapid reduction in plasma osmolality during hemodialysis (HD) may
      induce temporary gradients that promote the movement of water from the
      extracellular to the intracellular compartment, predisposing to the development
      of intradialytic hypotension (IDH). STUDY DESIGN: Observational cohort study.
      SETTING & PARTICIPANTS: 3,142 prevalent patients receiving thrice-weekly HD from
      a single dialysis provider organization. PREDICTOR: Predialysis calculated plasma
      osmolarity (calculated after the 2-day interval as 2 * serum sodium + serum urea
      nitrogen/2.8 + serum glucose/18). OUTCOME: Magnitude of systolic blood pressure
      (SBP) decline (predialysis SBP - nadir intradialytic SBP) and risk of IDH (SBP
      decline > 35 or nadir SBP < 90 mm Hg). MEASUREMENTS: Unadjusted and multivariable
      adjusted generalized linear models were fit to estimate the association of
      calculated osmolarity with intradialytic SBP decline and the odds of developing
      IDH. RESULTS: Mean age of participants was 62.6+/-15.2 (SD) years, 57.1% were
      men, and 61.0% had diabetes. Mean predialysis calculated osmolarity during follow
      up was 306.4 +/- 9.5 mOsm/L. After case-mix adjustment, each 10-mOsm/L increase
      in predialysis calculated osmolarity was associated with 1.48 (95% CI, 0.86-2.09)
      mm Hg (P < 0.001) greater decline in intradialytic SBP and 10% greater odds of
      IDH (OR, 1.10; 95% CI, 1.05-1.15). In adjusted models, lower predialysis sodium
      and higher serum urea nitrogen and serum glucose levels were associated with
      greater decline in intradialytic SBP. LIMITATIONS: Measured serum osmolality,
      timing of changes in intradialytic osmolality, dialysate osmolality, and
      dialysate temperature were not available. CONCLUSIONS: Higher predialysis
      calculated osmolarity is associated with greater decline in intradialytic SBP and
      greater risk of IDH in maintenance HD patients. Strategies to minimize rapid
      shifts in osmolality should be tested prospectively to minimize excess SBP
      decline in susceptible patients.

PMID- 25975967
TI  - The social distribution of dietary patterns. Traditional, modern and healthy
      eating among women in a Latin American city.
AB  - Popkin's nutrition transition model proposes that after the change from the
      traditional to the modern dietary pattern, another change toward "healthy eating"
      could occur. As health-related practices are associated with social position,
      with higher socioeconomic groups generally being the first to adopt public health
      recommendations, a gradient of traditional-modern-healthy dietary patterns should
      be observed between groups. The objectives of this article were: 1) to describe
      the dietary patterns of a representative sample of adult women; 2) to assess
      whether dietary patterns differentiate in traditional, modern and healthy; and 3)
      to evaluate the association of social position and dietary patterns. We conducted
      a survey in Tijuana, a Mexican city at the Mexico-United States (US) border.
      Women 18-65 years old (n = 2345) responded to a food frequency questionnaire, and
      questions about socioeconomic and demographic factors. We extracted dietary
      patterns through factor analysis, and employed indicators of economic and
      cultural capital, life course stage and migration to define social position. We
      evaluated the association of social position and dietary patterns with linear
      regression models. Three patterns were identified: "tortillas," "hamburgers" and
      "vegetables." Women in a middle position of economic and cultural capital scored
      higher in the "hamburgers" pattern, and women in upper positions scored higher in
      the "vegetables" pattern. Economic and cultural capitals and migration
      interacted, so that for women lower in economic capital, having lived in the US
      was associated with higher scores in the "hamburgers" pattern.

PMID- 25975968
TI  - A multi-SNP association test for complex diseases incorporating an optimal P
      value threshold algorithm in nuclear families.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have become a common approach
      to identifying single nucleotide polymorphisms (SNPs) associated with complex
      diseases. As complex diseases are caused by the joint effects of multiple genes,
      while the effect of individual gene or SNP is modest, a method considering the
      joint effects of multiple SNPs can be more powerful than testing individual SNPs.
      The multi-SNP analysis aims to test association based on a SNP set, usually
      defined based on biological knowledge such as gene or pathway, which may contain
      only a portion of SNPs with effects on the disease. Therefore, a challenge for
      the multi-SNP analysis is how to effectively select a subset of SNPs with
      promising association signals from the SNP set. RESULTS: We developed the Optimal
      P-value Threshold Pedigree Disequilibrium Test (OPTPDT). The OPTPDT uses general
      nuclear families. A variable p-value threshold algorithm is used to determine an
      optimal p-value threshold for selecting a subset of SNPs. A permutation procedure
      is used to assess the significance of the test. We used simulations to verify
      that the OPTPDT has correct type I error rates. Our power studies showed that the
      OPTPDT can be more powerful than the set-based test in PLINK, the multi-SNP FBAT
      test, and the p-value based test GATES. We applied the OPTPDT to a family-based
      autism GWAS dataset for gene-based association analysis and identified MACROD2
      AS1 with genome-wide significance (p-value=2.5*10(-6)). CONCLUSIONS: Our
      simulation results suggested that the OPTPDT is a valid and powerful test. The
      OPTPDT will be helpful for gene-based or pathway association analysis. The method
      is ideal for the secondary analysis of existing GWAS datasets, which may identify
      a set of SNPs with joint effects on the disease.

PMID- 25975969
TI  - Neuroprotective effects of intravenous lidocaine on early postoperative cognitive
      dysfunction in elderly patients following spine surgery.
AB  - BACKGROUND: This study aimed to evaluate the effects of lidocaine treatment on
      cognitive impairment in aged patients undergoing spine surgery and to explore the
      underlying mechanism. MATERIAL/METHODS: Patients were randomly divided into 2
      treatment groups: (1) saline (control) and (2) lidocaine. After induction of
      anesthesia, the lidocaine group received lidocaine as a bolus of 1 mg/kg over 5
      minutes, followed by a continuous infusion at 1.5 mg/kg/h until the end of the
      surgery. We examined the effects of lidocaine treatment on the improvement of
      cognitive function using the Mini-Mental State Examination (MMSE) at preoperation
      and 3 days postoperation. Serum samples were collected to assess the levels of IL
      6, TNF-alpha, MDA, S100beta, and NSE before inducing anesthesia, at the end of
      surgery, and 3 days after the end of surgery. RESULTS: We found that the MMSE
      scores in the lidocaine group were markedly higher than those in the control
      group at 3 days after surgery. Moreover, lidocaine treatment markedly suppressed
      the release of IL-6, S100beta, and NSE into the serum at the end of surgery and 3
      days after the end of surgery. In the control group, serum MDA levels increased
      by 3 days after the end of surgery. The lidocaine group had lower serum MDA
      levels than those in the control group. CONCLUSIONS: Lidocaine may be an
      effective neuroprotective agent in treating early postoperative cognitive
      dysfunction in elderly patients undergoing spine surgery.

PMID- 25975970
TI  - A novel pathogenic variant in PRF1 associated with hemophagocytic
      lymphohistiocytosis.
AB  - Familial Hemophagocytic Lymphohistiocytosis type 2 (FHL2) results from mutations
      in PRF1. We described two unrelated individuals who presented with FHL, in whom
      severely impaired NK cytotoxicity and decrease perforin expression was observed.
      DNA sequencing of PRF1 demonstrated that both were not only heterozygous for the
      p.54R > C/91A > V haplotype but also presented with the novel variant p.47G > V
      at the perforin protein. Perforin mRNA was found to be increased in a individual
      with that genotype. A carrier of the novel variant also demonstrated altered
      perforin mRNA and protein expression. Phylogenetic analysis and multiple
      alignments with perforin orthologous demonstrated a high level of conservation at
      Gly47. PolyPhen-2 and PROVEAN predicted p.47G > V to be "probably damaging" and
      "deleterious", respectively. A thermodynamic analysis showed that this variant
      was highly stabilizing, decreasing the protein internal energy. The ab initio
      perforin molecular modeling indicated that Gly47 is buried inside the hydrophobic
      core of the MACPF domain, which is crucial for the lytic pore formation and
      protein oligomerization. After the in silico induction of the p.47G > V mutation,
      Val47 increased the interactions with the surrounding amino acids due to its size
      and physical properties, avoiding a proper conformational change of the domain.
      To our knowledge, this is the first description supporting that p.47G > V is a
      pathogenic variant that in conjunction with p.54R > C/91A > V might result in the
      clinical phenotype of FHL2. 

PMID- 25975971
TI  - Treatment of Crohn's disease-related high perianal fistulas combining the mucosa
      advancement flap with platelet-rich plasma: a pilot study.
AB  - BACKGROUND: Healing rates after surgical closure for high perianal fistula in
      patients with Crohn's disease are even more disappointing than in patients with
      cryptoglandular fistulas. The objective was to improve healing rates by combining
      the well-known mucosal advancement flap with platelet-rich plasma. METHODS: A
      prospective pilot study was conducted in one tertiary referral centre.
      Consecutive patients with primary or recurrent Crohn's disease-related high
      perianal fistulas, defined as involving the middle and/or upper third parts of
      the anal sphincter complex, were included. A staged procedure was performed with
      non-cutting seton treatment for 3 months first, followed by a mucosal advancement
      flap with injection of platelet-rich plasma into the fistula tract. RESULTS: Ten
      consecutive patients were operated on between 2009 and 2014. Half (50%) of the
      patients had undergone previous fistula surgery. Mean follow-up was 23.3 months
      (SD 13.0). Healing of the fistula was 70% (95% confidence interval, 33-89%) at 1
      year. One (10%) patient had a recurrence, and in two (20%) patients, the fistula
      was persistent after treatment. An abscess occurred in one (10%) patient. The
      median post-operative Vaizey score was 8.0 (range 0-21), indicating a moderate to
      severe continence impairment. CONCLUSIONS: The results of combining the mucosal
      advancement flap with platelet-rich plasma in patients with Crohn's disease
      related high perianal fistulas are moderate with a healing rate of 70%. Further
      investigation is needed to determine the benefits and risks on continence status
      for this technique in this patient population.

PMID- 25975972
TI  - Sinoscopy: endoscopic washout of perineal sinus after abdominoperineal excision
      of the rectum.

PMID- 25975973
TI  - Successful endoscopic incision of pouch-anal stricture in a patient with
      ulcerative colitis.

PMID- 25975974
TI  - Intra-observer and inter-observer repeatability of ocular surface interferometer
      in measuring lipid layer thickness.
AB  - BACKGROUND: Tear lipid morphology is important for normal tear function.
      Recently, there have been clinical studies using interferometry to assess lipid
      layer thickness (LLT). The aim of the study is to examine the repeatability of a
      commercially available interferometer. METHODS: Two observers measured LLT in
      twenty Asian subjects (20 eyes) using an interferometer (LipiView(r) ocular
      surface interferometer, TearScience Inc, Morrisville, NC). Dry eye symptoms, tear
      break up time (TBUT) and corneal fluorescein staining were also prospectively
      evaluated. RESULTS: Data for 20 participants are presented for either right or
      left eye (randomly selected). The mean LLT +/- standard deviation of these
      participants was 53.53 +/- 14.59 nm. When a single observer repeated the imaging
      on the same day, the coefficient of repeatability was 16 nm and the 95% limits of
      agreement were between -11 nm and 18 nm. When a different observer repeated the
      scan, the coefficient of repeatability was 13 nm and limits of agreement were -9
      nm and 16 nm. LLT was not significantly associated with TBUT, presence of any
      corneal staining in any corneal zones, or symptomatic status. CONCLUSION: With
      the repeatability of measurements being known, the significance of LLT changes
      measured by this interferometer may be better interpreted. In this small Asian
      study, the LLT was lower than previously reported studies.

PMID- 25975976
TI  - Ruxolitinib- but not fedratinib-induced extreme thrombocytosis: the combination
      therapy with hydroxyurea and ruxolitinib is effective in reducing platelet count
      and splenomegaly/constitutional symptoms.

PMID- 25975977
TI  - Health-related quality of life after cataract surgery with the
      phacoemulsification technique and intraocular lens implantation.
AB  - PURPOSE: Disease-specific instruments have shown significant gains in measuring
      health-related quality of life (HRQoL) in subjects having cataract surgery.
      However, the usage of generic instruments has resulted in conflicting evidence.
      METHODS: In this prospective study, we have evaluated the impact of cataract
      surgery on subjects' HRQoL measured with a 15-dimension generic instrument, the
      15D. The HRQoL of cataract subjects was compared with that of an age- and gender
      standardized sample of the general population in Finland. A total of 152 subjects
      (mean age 74 years, 66% females) with a first-eye cataract surgery completed the
      15D questionnaire both before and 12 months after cataract surgery. RESULTS: When
      compared with the general population, cataract subjects had much lower HRQoL at
      baseline (mean difference 0.037 (95% CI: 0.020, 0.054), p < 0.001). At 12 months
      after cataract surgery, the overall utility index improved from the mean of 0.837
      to 0.855 (mean difference 0.018 (95% CI: 0.007, 0.029), p = 0.002). Significant
      improvement was observed on the following five dimensions: seeing, moving,
      hearing, usual activities and discomfort/symptoms in the 15D questionnaire.
      CONCLUSION: Our data indicate that at 12 months after first-eye cataract surgery,
      patients' HRQoL is slightly better than that before surgery. However, patients'
      postoperative HRQoL may remain lower than that of an age-and gender-standardized
      control population.

PMID- 25975978
TI  - Co-circulation of Clade C New World Arenaviruses: New geographic distribution and
      host species.
AB  - Clade C, of the New World Arenaviruses, is composed of only the Latino and
      Oliveros viruses and, besides the geographic range of their rodent reservoirs,
      the distribution of these viruses has been restricted to Bolivia and Argentina.
      In this study, the genetic detection and phylogenetic analysis of the complete S
      segment sequences of sympatric arenaviruses from Brazil revealed a new geographic
      distribution of clade C arenaviruses, as well as the association of Oliveros
      virus with a new rodent reservoir. 

PMID- 25975979
TI  - Exogenous Nkx2.5- or GATA-4-transfected rabbit bone marrow mesenchymal stem cells
      and myocardial cell co-culture on the treatment of myocardial infarction in
      rabbits.
AB  - The present study aimed to investigate the effects of Nkx2.5 or GATA-4
      transfection with myocardial extracellular environment co-culture on the
      transformation of bone marrow mesenchymal stem cells (BMSCs) into differentiated
      cardiomyocytes. Nkx2.5 or GATA-4 were transfected into myocardial extracellular
      environment co-cultured BMSCs, and then injected into the periphery of infarcted
      myocardium of a myocardial infarction rabbit model. The effects of these gene
      transfections and culture on the infarcted myocardium were observed and the
      results may provide an experimental basis for the efficient myocardial cell
      differentiation of BMSCs. The present study also suggested that these cells may
      provide a source and clinical basis for myocardial injury repair via stem cell
      transplantation. The present study examined whether Nkx2.5 or GATA-4 exogenous
      gene transfection with myocardial cell extracellular environment co-culture were
      able to induce the differentiation of BMSCs into cardiac cells. In addition, the
      effect of these transfected BMSCs on the repair of the myocardium following
      myocardial infarction was determined using New Zealand rabbit models. The results
      demonstrated that myocardial cell differentiation was significantly less
      effective following exogenous gene transfection of Nkx2.5 or GATA-4 alone
      compared with that of transfection in combination with extracellular environment
      co-culture. In addition, the results of the present study showed that exogenous
      gene transfection of Nkx2.5 or GATA-4 into myocardial cell extracellular
      environment co-cultured BMSCs was able to significantly enhance the ability to
      repair, mitigating the death of myocardial cells and activation of the myocardium
      in rabbits with myocardial infarction compared with those of the rabbits
      transplanted with untreated BMSCs. In conclusion, the exogenous Nkx2.5 and GATA-4
      gene transfection into myocardial extracellular environment co-cultured BMSCs
      induced increased differentiation into myocardial cells compared with that of
      gene transfection alone. Furthermore, significantly enhanced reparative effects
      were observed in the myocardium of rabbits following treatment with Nkx2.5-or
      GATA-4-transfected myocardial cell extracellular environment co-cultured BMSCs
      compared with those treated with untreated BMSCs.

PMID- 25975975
TI  - All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted
      treatment of acute promyelocytic leukaemia: a matched-pair analysis of the
      PETHEMA LPA-2005 and IC-APL studies.
AB  - Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans
      retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a
      comparison of idarubicin and daunorubicin has never been carried out. Two similar
      clinical trials using ATRA and chemotherapy for newly diagnosed APL were compared
      using matched-pair analysis. One was conducted by the PETHEMA/HOVON group with
      idarubicin and the other by the International Consortium on APL (IC-APL) using
      daunorubicin. Three hundred and fifty patients from the PETHEMA/HOVON cohort were
      matched with 175 patients in the IC-APL cohort, adjusting for the significantly
      unbalanced presenting features of the two entire cohorts. Complete remission (CR)
      rate was significantly higher in the PETHEMA/HOVON (94 %) than in the IC-APL
      cohort (85 %) (P = 0.002). The distribution of causes of induction failure and
      the time to achieve CR were similar in both cohorts. Patients who achieved CR had
      comparable cumulative incidence of relapse and disease-free survival rates, but
      lower overall and event-free survivals were observed in the IC-APL cohort, which
      was mainly due to a higher death rate during induction therapy. A higher death
      rate during consolidation therapy was also observed in the IC-APL. These results
      show that daunorubicin and idarubicin have similar antileukaemic efficacy in
      terms of primary resistance, molecular persistence, as well as molecular and
      haematological relapse rates when combined with ATRA in treatment of APL.
      However, a higher toxic death rate during induction and consolidation therapy was
      observed in the IC-APL cohort. This trial was registered at
      www.clinicaltrials.gov as #NCT00408278 [ClinicalTrials.gov]. 

PMID- 25975980
TI  - Potential impacts of bioprocessing of sweet potato: Review.
AB  - Sweet potato (Ipomoea batatas L.) is among the major food crops in the world and
      is cultivated in all tropical and subtropical regions particularly in Asia,
      Africa, and the Pacific. Asia and Africa regions account for 95% of the world's
      production. Among the root and tuber crops grown in the world, sweet potato ranks
      second after cassava. In previous decades, sweet potato represented food and feed
      security, now it offers income generation possibilities, through bioprocessing
      products. Bioprocessing of sweet potato offers novel opportunities to
      commercialize this crop by developing a number of functional foods and beverages
      such as sour starch, lacto-pickle, lacto-juice, soy sauce, acidophilus milk,
      sweet potato curd and yogurt, and alcoholic drinks through either solid state or
      submerged fermentation. Sweet potato tops, especially leaves are preserved as hay
      or silage. Sweet potato flour and bagassae are used as substrates for production
      of microbial protein, enzymes, organic acids, monosodium glutamate, chitosan,
      etc. Additionally, sweet potato is a promising candidate for production of
      bioethanol. This review deals with the development of various products from sweet
      potato by application of bioprocessing technology. To the best of our knowledge,
      there is no review paper on the potential impacts of the sweet potato
      bioprocessing.

PMID- 25975982
TI  - Malignant mesothelioma as an oxidative stress-induced cancer: An update.
AB  - Malignant mesothelioma (MM) is a relatively rare cancer that occurs almost
      exclusively following respiratory exposure to asbestos in humans. Its
      pathogenesis is closely associated with iron overload and oxidative stress in
      mesothelial cells. On fiber exposure, mesothelial cells accumulate fibers
      simultaneously with iron, which either performs physical scissor function or
      catalyzes free radical generation, leading to oxidative DNA damage such as strand
      breaks and base modifications, followed by activation of intracellular signaling
      pathways. Chrysotile, per se without iron, causes massive hemolysis and further
      adsorbs hemoglobin. Exposure to indigestible foreign materials also induces
      chronic inflammation, involving consistent generation of free radicals and
      subsequent activation of NALP3 inflammasomes in macrophages. All of these
      contribute to mesothelial carcinogenesis. Genomic alterations most frequently
      involve homozygous deletion of INK4A/4B, and other pathways such as Hippo and TGF
      beta pathways are also affected in MM. Recently, analyses of familial MM sorted
      out BAP1 as a novel responsible tumor suppressor gene, whose function is not
      fully elucidated. Five-year survival of mesothelioma is still ~8%, and this
      cancer is increasing worldwide. Connective tissue growth factor, a secretory
      protein creating a vicious cycle mediated by beta-catenin, has been recognized as
      a hopeful target for therapy, especially in sarcomatoid subtype. Recent research
      outcomes related to microRNAs and cancer stem cells also offer additional novel
      targets for the treatment of MM. Iron reduction as chemoprevention of
      mesothelioma is helpful at least in an animal preclinical study. Integrated
      approaches to fiber-induced oxidative stress would be necessary to overcome this
      currently fatal disease. 

PMID- 25975983
TI  - Corrigendum to "Gallic acid prevents nonsteroidal anti-inflammatory drug-induced
      gastropathy in rat by blocking oxidative stress and apoptosis" [Free Radic. Biol.
      Med. 49 (2010) 258-267].

PMID- 25975981
TI  - Nuclear glutaredoxin 3 is critical for protection against oxidative stress
      induced cell death.
AB  - Mammalian glutaredoxin 3 (Grx3) has been shown to be critical in maintaining
      redox homeostasis and regulating cell survival pathways in cancer cells. However,
      the regulation of Grx3 is not fully understood. In the present study, we
      investigate the subcellular localization of Grx3 under normal growth and
      oxidative stress conditions. Both fluorescence imaging of Grx3-RFP fusion and
      Western blot analysis of cellular fractionation indicate that Grx3 is
      predominantly localized in the cytoplasm under normal growth conditions, whereas
      under oxidizing conditions, Grx3 is translocated into and accumulated in the
      nucleus. Grx3 nuclear accumulation was reversible in a redox-dependent fashion.
      Further analysis indicates that neither the N-terminal Trx-like domain nor the
      two catalytic cysteine residues in the active CGFS motif of Grx3 are involved in
      its nuclear translocation. Decreased levels of Grx3 render cells susceptible to
      cellular oxidative stress, whereas overexpression of nuclear-targeted Grx3 is
      sufficient to suppress cells' sensitivity to oxidant treatments and reduce
      reactive oxygen species production. These findings provide novel insights into
      the regulation of Grx3, which is crucial for cell survival against environmental
      insults. 

PMID- 25975984
TI  - The emerging role of Nrf2 in mitochondrial function.
AB  - The transcription factor NF-E2 p45-related factor 2 (Nrf2; gene name NFE2L2)
      allows adaptation and survival under conditions of stress by regulating the gene
      expression of diverse networks of cytoprotective proteins, including antioxidant,
      anti-inflammatory, and detoxification enzymes as well as proteins that assist in
      the repair or removal of damaged macromolecules. Nrf2 has a crucial role in the
      maintenance of cellular redox homeostasis by regulating the biosynthesis,
      utilization, and regeneration of glutathione, thioredoxin, and NADPH and by
      controlling the production of reactive oxygen species by mitochondria and NADPH
      oxidase. Under homeostatic conditions, Nrf2 affects the mitochondrial membrane
      potential, fatty acid oxidation, availability of substrates (NADH and
      FADH2/succinate) for respiration, and ATP synthesis. Under conditions of stress
      or growth factor stimulation, activation of Nrf2 counteracts the increased
      reactive oxygen species production in mitochondria via transcriptional
      upregulation of uncoupling protein 3 and influences mitochondrial biogenesis by
      maintaining the levels of nuclear respiratory factor 1 and peroxisome
      proliferator-activated receptor gamma coactivator 1alpha, as well as by promoting
      purine nucleotide biosynthesis. Pharmacological Nrf2 activators, such as the
      naturally occurring isothiocyanate sulforaphane, inhibit oxidant-mediated opening
      of the mitochondrial permeability transition pore and mitochondrial swelling.
      Curiously, a synthetic 1,4-diphenyl-1,2,3-triazole compound, originally designed
      as an Nrf2 activator, was found to promote mitophagy, thereby contributing to the
      overall mitochondrial homeostasis. Thus, Nrf2 is a prominent player in supporting
      the structural and functional integrity of the mitochondria, and this role is
      particularly crucial under conditions of stress. 

PMID- 25975985
TI  - Nrf2 promotes survival following exposure to ionizing radiation.
AB  - Nrf2 is a transcription factor that promotes antioxidant and drug-metabolizing
      gene expression. It also regulates the transcription of genes involved in
      carbohydrate and lipid metabolism, NADPH regeneration, and heme and iron
      metabolism, as well as proteasome metabolism. Emerging research has identified
      Nrf2 as a critical factor for promoting survival of mammalian cells subjected to
      ionizing radiation. At a mechanistic level, Nrf2 promotes the repair of DNA
      damage and drives detoxification of superoxide that is generated hours to days
      after irradiation. This review summarizes research in these areas and discusses
      targeting of Nrf2 in radiation-resistant cancer and Nrf2's role in mitigating
      acute radiation syndrome. 

PMID- 25975986
TI  - The distinctive molecular, pathological and clinical characteristics of BRAF
      mutant colorectal tumors.
AB  - Several clinical series have demonstrated a notably low overall survival for
      colorectal cancer patients diagnosed with a BRAF-mutant tumor. A potentially
      interesting predictive role has also been suggested for BRAF-mutant colorectal
      cancer receiving anti-EGFR monoclonal antibodies. Although a global consensus
      exists in indicating BRAF as a prognostic factor with a possible predictive
      activity, the clinical use of BRAF mutational status in colorectal tumors is
      still controversial. This article reviews the current knowledge on the use and
      implications of BRAF mutational status in colorectal tumors, in order to define
      its present role in the clinical practice. Also suggested are possible treatment
      strategies in this prognostically challenging group of patients. Finally, a
      comprehensive outlook on future developments for specifically directed anti-BRAF
      therapy is illustrated. 

PMID- 25975988
TI  - Hepatotoxicity of green tea: an update.
AB  - Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam.
      Theaceae), is largely used for its potential health benefits such as reduction in
      risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to
      induce liver damage. Present work reviews the hepatic adverse reactions
      associated with GT-based herbal supplements, published by the end of 2008 to
      March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus
      and Google Scholar databases, without any language restriction. Moreover, some
      accessible databases on pharmacovigilance or phytovigilance were consulted. The
      causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of
      hepatotoxicity related to the consumption of herbal products containing GT were
      identified. The hepatic reactions involved mostly women (16/19); the kind of
      liver damage was generally classified as hepatocellular (16/19). The causality
      assessment between consumption of herbal preparation and hepatic reaction
      resulted as probable in eight cases and as possible in eleven cases. In seven
      cases, patients used preparations containing only GT, while twelve reactions
      involved patients who took multicomponent preparations (MC). The reactions
      induced by GT had a generally long latency (179.1 +/- 58.95 days), and the
      outcome was always resolution, with recovery time of 64.6 +/- 17.78 days. On the
      contrary, liver injury associated with MC had a shorter latency (44.7 +/- 13.85
      days) and was more serious in four cases that required liver transplantation and,
      when resolution occurred, the recovery time was longer (118.9 +/- 38.79). MC
      preparations contained numerous other components, many of which are suspected to
      induce liver damage, so it is difficult to ascribe the toxicity to one specific
      component, e.g., GT. Present data confirm a certain safety concern with GT, even
      if the number of hepatic reactions reported is low considering the great extent
      of use of this supplement. The mechanism of GT hepatotoxicity remains unclear,
      but factors related to the patient are becoming predominant. A major safety
      concern exists when GT is associated with other ingredients that can interact
      between them and with GT, enhancing the risk of liver damage. Patients should be
      discouraged from using herbal or dietary supplements containing complex mixtures
      and should be encouraged to use herbal and dietary supplement possibly under
      supervision of healthcare professionals. 

PMID- 25975989
TI  - Regulation of gene expression by CAR: an update.
AB  - The constitutive androstane receptor (CAR), a member of the nuclear receptor
      superfamily, is a well-known xenosensor that regulates hepatic drug metabolism
      and detoxification. CAR activation can be elicited by a large variety of
      xenobiotics, including phenobarbital (PB) which is not a directly binding CAR
      ligand. The mechanism of CAR activation is complex and involves translocation
      from the cytoplasm into the nucleus, followed by further activation steps in the
      nucleus. Recently, epidermal growth factor receptor (EGFR) has been identified as
      a PB-responsive receptor, and PB activates CAR by inhibiting the EGFR signaling.
      In addition to regulation of drug metabolism, activation of CAR has multiple
      biological end points such as modulation of xenobiotic-elicited liver injury, and
      the role of CAR in endobiotic functions such as glucose metabolism and
      cholesterol homeostasis is increasingly recognized. Thus, investigations on the
      molecular mechanism of CAR activation are critical for the real understanding of
      CAR-mediated processes. Here, we summarize the current understanding of
      mechanisms by which CAR activators regulate gene expression through cellular
      signaling pathways and the roles of CAR on xenobiotic-elicited hepatocellular
      carcinoma, liver injury, glucose metabolism and cholesterol homeostasis. 

PMID- 25975990
TI  - Unsaturated compounds induce up-regulation of CD86 on dendritic cells in the in
      vitro sensitization assay LCSA.
AB  - Unsaturated compounds are known to cause false-positive reactions in the local
      lymph node assay (LLNA) but not in the guinea pig maximization test. We have
      tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol,
      fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid,
      squalene, and arachidonic acid) in the loose-fit coculture-based sensitization
      assay (LCSA) to evaluate whether unspecific activation of dendritic cells is a
      confounder for sensitization testing in vitro. Eight out of 10 tested substances
      caused significant up-regulation of CD86 on dendritic cells cocultured with
      keratinocytes and would have been classified as sensitizers; only succinic acid
      was tested negative, and squalene had to be excluded from data analysis due to
      poor solubility in cell culture medium. Based on human data, only undecylenic
      acid can be considered a true sensitizer. The true sensitizing potential of 1
      octyn-3-ol is uncertain. Fumaric acid and its isomer maleic acid are not known as
      sensitizers, but their esters are contact allergens. A group of 18- to 20-carbon
      chain unsaturated fatty acids (linoleic acid, oleic acid, alpha-linolenic acid,
      and arachidonic acid) elicited the strongest reaction in vitro. This is possibly
      due to the formation of pro-inflammatory lipid mediators in the cell culture
      causing nonspecific activation of dendritic cells. In conclusion, both the LLNA
      and the LCSA seem to provide false-positive results for unsaturated fatty acids.
      The inclusion of T cells in dendritic cell-based in vitro sensitization assays
      may help to eliminate false-positive results due to nonspecific dendritic cell
      activation. This would lead to more accurate prediction of sensitizers, which is
      paramount for consumer health protection and occupational safety. 

PMID- 25975991
TI  - Decreased plasma thiol antioxidant barrier and selenoproteins as potential
      biomarkers for ongoing methylmercury intoxication and an individual protective
      capacity.
AB  - Manifestation of methylmercury (MeHg) toxicity depends on individual
      susceptibility to MeHg, as well as MeHg burden level. Therefore, biomarkers that
      reflect the protective capacity against MeHg are needed. The critical role of
      oxidative stress in the pathogenesis of MeHg cytotoxicity has been demonstrated.
      Because MeHg has high affinity for selenohydryl groups, sulfhydryl groups, and
      selenides, and causes posttranscriptional defects in selenoenzymes, proteins with
      selenohydryl and sulfhydryl groups should play a critical role in mediating MeHg
      induced oxidative stress. Here, plasma oxidative stress markers and
      selenoproteins were investigated in MeHg-intoxicated rats showing
      neuropathological changes after 4 weeks of MeHg exposure. The thiol antioxidant
      barrier (-SHp) level significantly decreased 2 weeks after MeHg exposure, which
      is an early stage at which no systemic oxidative stress, histopathological
      changes, or clinical signs were detected. Diacron reactive oxidant metabolite (d
      ROM) levels significantly increased 3 weeks after MeHg exposure, indicating the
      occurrence of systemic oxidative stress. Rats treated with lead acetate or
      cadmium chloride showed no changes in levels of -SHp and d-ROM. Selenoprotein P1
      abundance significantly decreased in MeHg-treated rats, whereas it significantly
      increased in rats treated with Pb or Cd. Plasma selenium-dependent glutathione
      peroxidase (GPx3) activity also significantly decreased after MeHg exposure,
      whereas plasma non-selenoenzyme glutathione reductase activity significantly
      increased in MeHg-treated rats. The results suggest that decreased capacity of 
      SHp and selenoproteins (GPx3 and selenoprotein P) can be useful biomarkers of
      ongoing MeHg cytotoxicity and the individual protective capacity against the MeHg
      body burden.

PMID- 25975987
TI  - Progress and future of in vitro models to study translocation of nanoparticles.
AB  - The increasing use of nanoparticles in products likely results in increased
      exposure of both workers and consumers. Because of their small size, there are
      concerns that nanoparticles unintentionally cross the barriers of the human body.
      Several in vivo rodent studies show that, dependent on the exposure route, time,
      and concentration, and their characteristics, nanoparticles can cross the lung,
      gut, skin, and placental barrier. This review aims to evaluate the performance of
      in vitro models that mimic the barriers of the human body, with a focus on the
      lung, gut, skin, and placental barrier. For these barriers, in vitro models of
      varying complexity are available, ranging from single-cell-type monolayer to
      multi-cell (3D) models. Only a few studies are available that allow comparison of
      the in vitro translocation to in vivo data. This situation could change since the
      availability of analytical detection techniques is no longer a limiting factor
      for this comparison. We conclude that to further develop in vitro models to be
      used in risk assessment, the current strategy to improve the models to more
      closely mimic the human situation by using co-cultures of different cell types
      and microfluidic approaches to better control the tissue microenvironments are
      essential. At the current state of the art, the in vitro models do not yet allow
      prediction of absolute transfer rates but they do support the definition of
      relative transfer rates and can thus help to reduce animal testing by setting
      priorities for subsequent in vivo testing. 

PMID- 25975992
TI  - Pubertal exposure to di-(2-ethylhexyl)-phthalate inhibits G9a-mediated histone
      methylation during spermatogenesis in mice.
AB  - The increasing incidence of male reproductive impairments has been associated
      with di-(2-ethylhexyl)-phthalate (DEHP) exposure. However, mechanisms involved
      are lacking. We exposed 4-week-old male C57BL/6j mice to DEHP by gavage at 0,
      125, 250 or 500 mg/kg body weight/day for 28 consecutive days. Our data showed
      that pubertal exposure to DEHP induces sperm count reduction as well as
      histological abnormalities in seminiferous epithelium and apoptosis of post
      meiotic germ cells, and these effects are concomitant with reduction of
      testosterone levels and its steroidogenic gene expression. Moreover, the
      expressions of estrogen receptor ERbeta and nuclear receptors Nr0b1, Nr0b2 are
      increased. The expression of Nr5a2 which is the inducer of steroidogenesis is
      significantly reduced. Furthermore, spermatogonial stem cell (SSC) self-renewal,
      differentiation and meiosis were significantly impaired, and the epigenetic
      regulator G9a-mediated histone methylation was decreased following DEHP exposure.
      Our results suggest that the DEHP-induced male reproductive impairments may
      depend on its estrogenic action on estrogen receptor and nuclear receptor, and
      involve inhibition of steroidogenesis, SSC self-renewal and meiosis, which may be
      attributed to the down-regulation of G9a-mediated histone methylation.

PMID- 25975993
TI  - Sero-prevalence of dengue infections in the Kassala state in the eastern part of
      the Sudan in 2011.
AB  - Dengue fever is a vector-borne disease that is transmitted to humans by infected
      Aedes aegypti mosquitoes. The eastern part of the Sudan is one of the regions
      that is affected by dengue virus circulation. In this study, we estimated the
      prevalence of dengue infections in the Kassala state in the eastern part of the
      Sudan. The study objective was to estimate the sero-prevalence of dengue IgG/IgM
      antibodies in the Kassala locality in 2011. This was a cross sectional community
      based study that utilized a multi-stage cluster sampling technique regarding the
      probability sampling the study participants. Capture ELISA serological techniques
      were used for both IgM and IgG, with the specific cut-offs for each set by the
      manufacturer. The prevalence of dengue infection was found to be 9.4% (95% CI:
      7.1-12.3). In conclusion, there is evidence that the dengue virus is being
      transmitted in Kassala. Disease surveillance, including the clinical, serological
      and entomological components, should be strengthened, and additional
      epidemiological studies are needed to better understand of the disease burden and
      effects in the area. 

PMID- 25975994
TI  - Determinants of cervical cancer screening adherence in urban areas of Nakhon
      Ratchasima Province, Thailand.
AB  - Cervical cancer is the most common disease among Thai women. The cervical cancer
      mortality rate has increased in the previous decade. Therefore, this cross
      sectional study was conducted to examine the factors associated with cervical
      cancer screening adherence. Stratified sampling with the proportional to size
      method was used to select registered women aged 30-60 years. Of the 700 self
      administered questionnaires distributed during July and September of 2012, 675
      were returned, resulting in a response rate of 96.2%. Approximately 65.4% of the
      women were considered to be adherent to cervical cancer screening (i.e.,
      maintainers) as defined by at least one screening within the recommended 5-year
      screening interval and the expectation of attending a screening in the future.
      Chi-square tests revealed that occupation, marital status, number of children,
      sexual activity, health insurance scheme, history of oral contraceptive pill use,
      perceived barriers, perceived benefits, and knowledge about cervical cancer
      prevention were significantly associated with cervical cancer screening
      adherence. After adjusting for occupation, marital status, number of children,
      and health insurance in the model, perceived barriers (Adj OR=1.97, 95% CI=1.24
      3.10) and knowledge (Adj OR=1.65, 95% CI=1.13-2.41) remained significant
      predictors of cervical cancer screening adherence. These findings suggest that
      the non-housewives, women of single/separated/divorced/widowed status, and women
      with no children should be the first priorities for getting Pap tests. Strategies
      for overcoming the barriers of these women, such as using mobile units for
      cervical cancer screening, should be promoted. Education programs should be
      strengthened and promoted to overcome negative perceptions and knowledge
      deficiencies. 

PMID- 25975995
TI  - Management of De Novo CML and Imatinib-Induced Acute Rhabdomyolysis With the
      Second-Generation TKI, Dasatinib.

PMID- 25975996
TI  - Quetiapine concentrations during exclusive breastfeeding and maternal quetiapine
      use.

PMID- 25975997
TI  - Hypertrophic Cranial Pachymeningitis Caused by Pseudomonas stutzeri Associated
      With Connective Tissue Disease.

PMID- 25975998
TI  - Ischemic stroke after influenza vaccination.

PMID- 25975999
TI  - Exact and approximate moment closures for non-Markovian network epidemics.
AB  - Moment-closure techniques are commonly used to generate low-dimensional
      deterministic models to approximate the average dynamics of stochastic systems on
      networks. The quality of such closures is usually difficult to asses and
      furthermore the relationship between model assumptions and closure accuracy are
      often difficult, if not impossible, to quantify. Here we carefully examine some
      commonly used moment closures, in particular a new one based on the concept of
      maximum entropy, for approximating the spread of epidemics on networks by
      reconstructing the probability distributions over triplets based on those over
      pairs. We consider various models (SI, SIR, SEIR and Reed-Frost-type) under
      Markovian and non-Markovian assumption characterising the latent and infectious
      periods. We initially study with care two special networks, namely the open
      triplet and closed triangle, for which we can obtain analytical results. We then
      explore numerically the exactness of moment closures for a wide range of larger
      motifs, thus gaining understanding of the factors that introduce errors in the
      approximations, in particular the presence of a random duration of the infectious
      period and the presence of overlapping triangles in a network. We also derive a
      simpler and more intuitive proof than previously available concerning the known
      result that pair-based moment closure is exact for the Markovian SIR model on
      tree-like networks under pure initial conditions. We also extend such a result to
      all infectious models, Markovian and non-Markovian, in which susceptibles escape
      infection independently from each infected neighbour and for which infectives
      cannot regain susceptible status, provided the network is tree-like and initial
      conditions are pure. This works represent a valuable step in enriching intuition
      and deepening understanding of the assumptions behind moment closure
      approximations and for putting them on a more rigorous mathematical footing. 

PMID- 25976000
TI  - Identification of Mycobacterium abscessus complex and M. abscessus subsp.
      massiliense culture isolates by real-time assays.

PMID- 25976001
TI  - Antifungal activity of clotrimazole against Candida albicans depends on carbon
      sources, growth phase and morphology.
AB  - Vulvovaginal candidiasis, a superficial infection caused predominantly by the
      pathogenic fungus Candida albicans, is frequently treated with clotrimazole. Some
      drug formulations contain lactate for improved solubility. Lactate may modify C.
      albicans physiology and drug sensitivity by serving as a carbon source for the
      fungus and/or affecting local pH. Here, we explored the effects of lactate, in
      combination with pH changes, on C. albicans proliferation, morphology and
      clotrimazole sensitivity. Moreover, we determined the influence of growth phase
      and morphology per se on drug sensitivity. We showed that utilization of lactate
      as a carbon source did not promote fast fungal proliferation or filamentation.
      Lactate had no influence on clotrimazole-mediated killing of C. albicans in
      standard fungal cultivation medium but had an additive effect on the fungicidal
      clotrimazole action under in vitro vagina-simulative conditions. Moreover,
      clotrimazole-mediated killing was growth-phase and morphology dependent. Post
      exponential cells were resistant to the fungicidal action of clotrimazole, whilst
      logarithmic cells were sensitive, and hyphae showed the highest susceptibility.
      Finally, we showed that treatment of pre-formed C. albicans hyphae with sublethal
      concentrations of clotrimazole induced a reversion to yeast-phase growth. As C.
      albicans hyphae are considered the pathogenic morphology during mucosal
      infections, these data suggest that elevated fungicidal activity of clotrimazole
      against hyphae plus clotrimazole-induced hyphae-to-yeast reversion may help to
      dampen acute vaginal infections by reducing the relative proportion of hyphae and
      thus shifting to a non-invasive commensal-like population. In addition, lactate
      as an ingredient of clotrimazole formulations may potentiate clotrimazole killing
      of C. albicans in the vaginal microenvironment. 

PMID- 25976002
TI  - Anti-Streptococcus pneumoniae and rotavirus IgG levels in HIV-positive women do
      not correlate with maternal status and infant morbidity and mortality.

PMID- 25976003
TI  - Epidemiology of domestically acquired hepatitis E virus infection in Japan:
      assessment of the nationally reported surveillance data, 2007-2013.
AB  - In recent years, there has been an increase in the number of reported hepatitis E
      virus (HEV) infections from developed countries. To describe recent trends in
      notification and potential risk groups and risk factors in Japan, HEV infection
      cases and demographic, food consumption, clinical and laboratory data reported
      during 2007-2013 were analysed. In total, 530 HEV infections were reported during
      2007-2013. Amongst 462 domestic cases, the mean age was 56.5 years (sd 13.9) and
      80.1 % were male. Forty-three cases (9.3 %) were asymptomatic, amongst which 11
      were detected from blood donations. Whilst ~50 cases were reported annually
      during 2007-2011, the number of reported cases increased to 121 in 2012 and 126
      in 2013. The increase was characterized by a rise in the number of domestic,
      symptomatic cases (P = 0.05) and cases confirmed by anti-HEV IgA detection (P <
      0.01). HEV genotypes G3 and G4 were consistently dominant. The major suspected
      source of infection was food-borne, and the major suspected foods were pig, wild
      boar and deer meat. The observed increase during 2012-2013 was most likely due to
      the coverage of the anti-HEV IgA assay by the National Health Insurance system in
      Japan in October 2011 and its acceptance for surveillance purposes. However, the
      increase was not associated with detection of asymptomatic cases. Moreover, males
      aged 50-69 years remained as the high-risk group, and pork and other meats
      continued to be the most suspected items. Our findings indicated that HEV
      infection is an emerging and important public health concern in Japan. 

PMID- 25976004
TI  - Genital carriage of the genus Haemophilus in pregnancy: species distribution and
      antibiotic susceptibility.
AB  - Recent reports have hypothesized that colonization of the maternal genital tract
      with non-capsulated Haemophilus influenzae could result in neonatal invasive
      disease. In this study, genital carriage of the genus Haemophilus was
      investigated in 510 pregnant women attending an Italian hospital for routine
      controls. Overall, vaginal carriage of the genus Haemophilus was 9.0 % (46/510).
      A high colonization rate with Haemophilus parainfluenzae (37/510, 7.3 %) was
      found; other species, such as Haemophilus pittmaniae (7/510, 1.4 %) and
      Haemophilus haemolyticus (2/510, 0.4 %), were detected for the first time in the
      genital flora by 16S rRNA gene sequencing. Notably, no H. influenzae was
      identified, in agreement with previous investigations indicating that this
      species is rarely isolated from the genito-urinary tract of pregnant women. No
      antibiotic resistance was detected in H. pittmaniae and H. haemolyticus, but
      quite a high degree of ampicillin (10/37, 27 %) and ciprofloxacin (3/37, 8.1 %)
      resistance was observed in H. parainfluenzae. Five ampicillin-resistant isolates
      were beta-lactamase producers, whereas five isolates exhibited a beta-lactamase
      negative ampicillin-resistant (BLNAR) phenotype. Sequencing of penicillin-binding
      protein 3 revealed that Val511Ala, Asn526Ser, Ala530Ser and Thr574Ala changes
      were associated with BLNAR phenotypes. Two ciprofloxacin-resistant isolates
      carried substitutions in both GyrA (Ser84Phe and Asp88Tyr) and ParC (Ser84Tyr and
      Met198Leu); the other ciprofloxacin-resistant isolate had substitutions in ParC,
      only (Ser138Thr and Met198Leu). In conclusion, ~10 % of pregnant women carried a
      species of Haemophilus in their genital tract. The emergence of non-beta
      lactamase-mediated resistance in genital H. parainfluenzae is a matter of concern
      because of the risk of mother-to-baby transmission. 

PMID- 25976005
TI  - Molecular characterization of vancomycin-resistant Enterococcus faecium strains
      isolated from carriage and clinical samples in a tertiary hospital, Turkey.
AB  - This study aimed to determine the presence of vancomycin resistance (vanA and
      vanB) and virulence genes (esp, asa1, gelE, ace, hyl, cylA, cpd and ebpA) in
      vancomycin-resistant Enterococcus faecium (VREfm) strains and to analyse the
      clonal relationships among the strains. E. faecium strains were identified from
      rectal and clinical specimens by biochemical tests and the API-20 Strep kit.
      Susceptibility testing was performed using disc-diffusion and broth-dilution
      methods. PFGE was used for molecular typing of the VREfm strains. The vancomycin
      resistance and virulence genes were amplified by two-step multiplex PCR. All 55
      VREfm isolates were resistant to penicillin G, ampicillin and high-level
      gentamicin but were susceptible to quinupristin/dalfopristin and linezolid.
      Multiplex PCR analysis indicated that all isolates harboured vanA and that 41 (75
      %) were positive for virulence genes. The esp gene was the most common virulence
      factor and was detected in nine (41 %) invasive and 32 (96.7 %) non-invasive
      isolates. Multiple virulence genes were observed only in two non-invasive
      isolates; one harboured esp and ebpA and the other harboured esp, ebpA, asa1,
      gelE and cpd. PFGE typing yielded 16 different types, seven of which were
      clusters with two to 14 strains each. The clustering rates of the rectal swab,
      blood and urine isolates were 72.7 %, 61.5 % and 87.5 %, respectively. The
      genetic similarity observed among the VREfm isolates indicated cross-transmission
      in the hospital. Further studies on the virulence factors present in the strains
      might provide insight into the acquisition of these traits and their contribution
      to increased prevalence of VREfm. 

PMID- 25976006
TI  - Acanthamoeba keratitis: improving the Scottish diagnostic service for the rapid
      molecular detection of Acanthamoeba species.
AB  - Acanthamoeba species are responsible for causing the potentially sight
      threatening condition, Acanthamoeba keratitis, which is commonly associated with
      contact lens use. In this report, we highlight the challenges faced using
      conventional laboratory identification methods to identify this often under
      reported pathogen, and discuss the reasons for introducing the first national
      service in Scotland for the rapid and sensitive molecular identification of
      Acanthamoeba species. By comparing culture and molecular testing data from a
      total of 63 patients (n = 80 samples) throughout Scotland presenting with ocular
      eye disease, we describe the improvement in detection rates where an additional
      four positive cases were identified using a molecular assay versus culture. The
      testing of a further ten patients by confocal imaging is also presented. This
      report emphasizes the importance of continuing to improve clinical laboratory
      services to ensure a prompt, correct diagnosis and better prognosis, in addition
      to raising awareness of this potentially debilitating opportunistic pathogen. 

PMID- 25976008
TI  - Calculation of the stability of nonperiodic solids using classical force fields
      and the method of increments: N2O as an example.
AB  - Combining classical force fields for the Hartree-Fock (HF) part and the method of
      increments for post-HF contributions, we calculate the cohesive energy of the
      ordered and randomly disordered nitrous oxide (N2 O) solid. At 0 K, ordered N2 O
      is most favorable with a cohesive energy of -27.7 kJ/mol. At temperatures above
      60 K, more disordered structures become compatible and a phase transition to
      completely disordered N2 O is predicted. Comparison with experiment in literature
      suggests that experimentally prepared N2 O crystals are mainly disordered due to
      a prohibitively high activation energy of ordering processes. (c) 2015 Wiley
      Periodicals, Inc. 

PMID- 25976007
TI  - An audit of the laboratory diagnosis of cryptosporidiosis in England and Wales.
AB  - To assess the level of practice consistent with UK national standards for
      Cryptosporidium testing, an audit was performed of 156 publicly funded clinical
      microbiology laboratories in England and Wales between August 2013 and April
      2014. Responses were received from 85 (54 %) laboratories. First line diagnostic
      methods used were mainly microscopy with modified Ziehl-Neelsen (mZN) or auramine
      phenol (AP) staining (68/85, 80 %), enzyme immunoassays (EIAs) (16/85, 19 %) or
      in-house PCR (1/85, 1 %). The use of EIAs was more widespread than reported
      previously. Various methods were used for confirmation of positive EIA reactions
      and laboratories frequently resorted to sending samples to the national reference
      laboratory for this purpose, indicating that guidance is required for performance
      monitoring and confirmation of positive reactions. Laboratory positivity rates
      were related to the diagnostic test used, with highest median rates reported by
      those using PCR, EIAs or AP microscopy, and the lowest by those using mZN
      microscopy. One-third of responding laboratories (28/85, 33 %) routinely tested
      all stools for Cryptosporidium. However, 16 (19 %) laboratories used stool
      consistency to decide whether to test for this parasite. Other selection criteria
      included patient age (n = 18; 21 % laboratories), history or clinical details (n
      = 40; 47 %), duration of hospitalization (n = 18; 21 %) or clinician requests (n
      = 25; 29 %). To encourage laboratories to test all stools submitted for the
      investigation of diarrhoeal illness for Cryptosporidium, revision of the guidance
      in the national standards is under way. This will enable improved assessment of
      the burden of illness and ability to monitor outbreaks, and measure changes in
      reported cases.

PMID- 25976009
TI  - Impact of a U.S. antismoking national media campaign on beliefs, cognitions and
      quit intentions.
AB  - In 2012, the Centers for Disease Control and Prevention launched a national
      tobacco education campaign, Tips From Former Smokers, that consisted of graphic,
      emotionally evocative, testimonial-style advertisements. This longitudinal study
      examines changes in beliefs, tobacco-related cognitions and intentions to quit
      smoking among U.S. adult smokers after a 12-week airing of the campaign (n = 4040
      adult smokers pre- and post-campaign). Exposure to the campaign was associated
      with greater odds of intending to quit within the next 30 days [odds ratio (OR) =
      1.28, P < 0.01] and within the next 6 months (OR = 1.12, P < 0.05), and quit
      intentions were stronger among respondents with greater campaign exposure (OR =
      1.12, P < 0.01). Campaign exposure was also associated with significant changes
      in beliefs about smoking-related risks (ORs = 1.15-2.40) and increased worries
      about health (b = 0.30, P < 0.001). Based on study change rates applied to U.S.
      census data, an estimated 566 000 additional U.S. smokers reported their
      intention to quit smoking within the next 6 months as a result of viewing
      campaign advertisements. Campaign effects were consistent with the theory of
      reasoned action and an expanding body of research demonstrating that graphic,
      emotional advertisements are highly effective for prompting positive cessation
      related cognitions and behavioral intentions. 

PMID- 25976010
TI  - Association of a neurokinin 3 receptor polymorphism with the anterior basal
      forebrain.
AB  - The neuropeptide neurokinin 3 (NK3) and its receptor modulate cholinergic
      activity of the basal forebrain (BF) and are implicated in learning and memory.
      In Alzheimer's disease, the rs2765 single-nucleotide polymorphism (SNP) of the
      NK3 receptor-coding gene TACR3 was correlated with the right hippocampus volume.
      Here, we studied the association of the rs2765 SNP with magnetic resonance
      imaging-based volumes of the BF and hippocampus in a population-based sample of
      1967 participants between 21 and 90 years of age. The rs2765 SNP was
      significantly associated with the most anterior BF volume corresponding to the
      medial septum/diagonal band, and with a significantly steeper age-related volume
      decline. The rs2765 SNP was not associated with other BF subvolumes or
      hippocampus volumes. Apolipoprotein E epsilon4 showed no correlation with any
      brain volume or global cognition. Our findings in a large population-based sample
      suggest an association of an NK3 receptor SNP with age-related decline of rostral
      cholinergic BF volume.

PMID- 25976011
TI  - Mitochondrial modulators in experimental Huntington's disease: reversal of
      mitochondrial dysfunctions and cognitive deficits.
AB  - Huntington's disease (HD) is a chronic neurodegenerative condition involving
      impaired mitochondrial functions. The present study evaluates the therapeutic
      potential of combined administration of mitochondrial modulators: alpha-lipoic
      acid and acetyl-l-carnitine on mitochondrial dysfunctions in 3-NP-induced HD. Our
      results reveal 3-NP administration resulted in compromise of mitochondrial
      functions in terms of: (1) impaired activity of mitochondrial respiratory chain
      enzymes, altered cytochrome levels, reduced histochemical staining of complex-II
      and IV, reduced in-gel activity of complex-I to V, and reduced mRNA expression of
      respiratory chain complexes; (2) enhanced mitochondrial oxidative stress
      indicated by increased malondialdehyde, protein carbonyls, reactive oxygen
      species and nitrite levels, along with decreased Mn-superoxide dismutase and
      catalase activity; (3) mitochondrial structural changes measured by mitochondrial
      swelling, reduced mitochondrial membrane potential and ultra-structure changes;
      (4) increased cytosolic cytochrome c levels, caspase-3 and -9 activity along with
      altered expression of apoptotic proteins (AIF, Bim, Bad, and Bax); and (5)
      impaired cognitive functions assessed using Morris water maze and Y-maze.
      Combination of mitochondrial modulators (alpha-lipoic acid + acetyl-l-carnitine)
      on the other hand ameliorated 3-NP-induced mitochondrial dysfunctions, oxidative
      stress, histologic alterations, and behavioral deficits, suggesting their
      therapeutic efficacy in the management of HD.

PMID- 25976013
TI  - Antifungal activity of the ribosome-inactivating protein BE27 from sugar beet
      (Beta vulgaris L.) against the green mould Penicillium digitatum.
AB  - The ribosome-inactivating protein BE27 from sugar beet (Beta vulgaris L.) leaves
      is an apoplastic protein induced by signalling compounds, such as hydrogen
      peroxide and salicylic acid, which has been reported to be involved in defence
      against viruses. Here, we report that, at a concentration much lower than that
      present in the apoplast, BE27 displays antifungal activity against the green
      mould Penicillium digitatum, a necrotrophic fungus that colonizes wounds and
      grows in the inter- and intracellular spaces of the tissues of several edible
      plants. BE27 is able to enter into the cytosol and kill fungal cells, thus
      arresting the growth of the fungus. The mechanism of action seems to involve
      ribosomal RNA (rRNA) N-glycosylase activity on the sarcin-ricin loop of the major
      rRNA which inactivates irreversibly the fungal ribosomes, thus inhibiting protein
      synthesis. We compared the C-terminus of the BE27 structure with antifungal plant
      defensins and hypothesize that a structural motif composed of an alpha-helix and
      a beta-hairpin, similar to the gamma-core motif of defensins, might contribute to
      the specific interaction with the fungal plasma membranes, allowing the protein
      to enter into the cell. 

PMID- 25976014
TI  - Does transcranial stimulation for motor evoked potentials (TcMEP) worsen seizures
      in epileptic patients following spinal deformity surgery?
AB  - PURPOSE: To investigate the effect of Transcranial Motor Evoked Potentials
      (TcMEP) in increasing the severity or frequency of post-operative seizures in
      patients undergoing deformity corrective spine surgery with a known history of
      seizures pre-operatively. METHODS: The information on all patients with history
      of epilepsy/seizures who underwent spinal TcMEP cord monitoring for deformity
      correction surgery was retrospectively collected through a review of the hospital
      notes. The benefits of TcMEP in the early detection of potential cord ischemia
      were deemed by the operating surgeon to outweigh the increased risks of seizures,
      tongue biting, etc. Data on age, gender, pre-operative diagnosis, curve type,
      intra-operative monitoring alerts, duration of hospital stay, and post-operative
      in-hospital seizures were collected. Additionally, the patients were contacted
      following discharge and data on any change in the frequency of the seizures or an
      alteration in seizure-related medication post-operatively was also collected.
      RESULTS: The records of 449 consecutively monitored patients were reviewed and 12
      (2.7 %) patients with a history of seizures pre-operatively were identified. The
      mean age was 23 (9-59) years, 7 females, 11 scoliosis corrections (4
      neuromuscular, 1 degenerative, 6 idiopathic adolescent), and one sagittal balance
      correction surgery. Intra-operatively, all patients had TcMEP monitoring, were
      catheterised, and had no neuromonitoring alerts or record of tongue biting or
      laceration. Post-operatively, the mean hospital stay was 12 (4-25) days with no
      recorded seizures. At a mean of 23 (12-49) months post-discharge, none of the
      patients reported a worsening of seizures (pattern or frequency) or required an
      alteration in the seizure-related medications. CONCLUSION: TcMEP does not appear
      to trigger intra-operative or post-operative seizures and is not associated with
      deterioration in the seizure control of patients suffering seizures pre
      operatively.

PMID- 25976012
TI  - Factor XI and contact activation as targets for antithrombotic therapy.
AB  - The most commonly used anticoagulants produce therapeutic antithrombotic effects
      either by inhibiting thrombin or factor Xa (FXa) or by lowering the plasma levels
      of the precursors of these key enzymes, prothrombin and FX. These drugs do not
      distinguish between thrombin generation contributing to thrombosis from thrombin
      generation required for hemostasis. Thus, anticoagulants increase bleeding risk,
      and many patients who would benefit from therapy go untreated because of
      comorbidities that place them at unacceptable risk for hemorrhage. Studies in
      animals demonstrate that components of the plasma contact activation system
      contribute to experimentally induced thrombosis, despite playing little or no
      role in hemostasis. Attention has focused on FXII, the zymogen of a protease
      (FXIIa) that initiates contact activation when blood is exposed to foreign
      surfaces, and FXI, the zymogen of the protease FXIa, which links contact
      activation to the thrombin generation mechanism. In the case of FXI,
      epidemiologic data indicate this protein contributes to stroke and venous
      thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial
      showing that reduction of FXI may be more effective than low molecular weight
      heparin at preventing venous thrombosis during knee replacement surgery provides
      proof of concept for the premise that an antithrombotic effect can be uncoupled
      from an anticoagulant effect in humans by targeting components of contact
      activation. Here, we review data on the role of FXI and FXII in thrombosis and
      results of preclinical and human trials for therapies targeting these proteins. 

PMID- 25976015
TI  - Bacterial colonization of VEPTR implants under repeated expansions in children
      with severe early onset spinal deformities.
AB  - PURPOSE: Historically, severe spinal and thoracic deformities in children were
      treated with early long spinal fusions. This prevented further growth of the
      spine and thorax and often led to small stiff thoraces. Therefore, growth
      retaining implants, like vertical expandable titanium ribs (VEPTR), were
      developed to stimulate thoracic and spinal growth. To accommodate growth, these
      implants have to be expanded every 6 months. Infection rates of up to 2 % per
      procedure are reported. Exchange of implant parts allows analyzing the
      development of implant-related infections and subclinical colonizations. METHODS:
      In this prospective study, all patients undergoing repeat VEPTR expansion
      procedures at our institution were included. Preoperatively, clinical signs of
      infection were documented, and blood samples were taken. The removed implants
      were treated by sonication and microbiologically analyzed. The clinical follow-up
      was documented. RESULTS: From January 2009 to May 2012, 39 children with 163 re
      operations were included. Four of the 39 patients (10 %) developed clinical
      apparent infections and had implant removal. These were excluded and analyzed
      separately. Of 144 procedures, implant parts were eligible for analysis. Implant
      colonization was detected by sonication in 24 of 144 (16 %) operations in 18 out
      of 39 (46 %) patients. Repeated detection occurred in 5 (14 %) patients. No risk
      factors for colonization could be identified. CONCLUSION: The rate of implant
      colonization is 4.5 times higher than the rate of manifest infections in VEPTR
      patients. Colonization may lead to a manifest infection over time. The knowledge
      of persistent implant colonization may change the treatment algorithm in patients
      with growth-retaining implants.

PMID- 25976016
TI  - New concept of pathogenesis of impaired circulation in traumatic cervical spinal
      cord injury and its impact on disease severity: case series of four patients.
AB  - PURPOSE: The purpose of this study is to justify a new concept of the
      pathogenesis of secondary changes in the cervical spinal cord, and its
      correlation with the depth of development of neurological disorders in spinal
      injury. METHODS: Standard magnetic resonance imaging examination and angiography
      of the cervical and vertebral arteries of four patients were performed to
      diagnose the prevalence rate of ischemia and edema, and examine the spinal cord
      vasculature. Correlation of the data obtained with the neurological status was
      performed. RESULTS: Collateral circulation is most apparent in the upper-cervical
      region, above the C4 vertebra. Following occlusion of the vertebral artery, the
      circulation above the C4 vertebra is performed by collaterals of the ascending
      cervical artery. With extensive damage to the spinal cord, the intensity of edema
      and ischemia can be regarded as the effect of damage to radicular medullary
      arteries, which are injured in the intervertebral foramen. Secondary changes of
      the spinal cord are most apparent by impaired circulation in the artery of
      cervical enlargement. CONCLUSIONS: Collateral circulation is a significant factor
      that limits the damage to the cervical spinal cord. Impaired circulation in the
      artery of cervical enlargement is significant in extension of perifocal ischemia.
      The appearance of early arteriovenous shunting in the region of a primary spinal
      cord injury (contusion focus) by angiography is pathognomonic. The data obtained
      open a perspective for the endovascular treatment of spinal cord injury.

PMID- 25976017
TI  - Schistosoma mansoni and HIV infection in a Ugandan population with high HIV and
      helminth prevalence.
AB  - OBJECTIVES: Recent reports suggest that Schistosoma infection may increase the
      risk of acquiring human immunodeficiency virus (HIV). We used data from a large
      cross-sectional study to investigate whether Schistosoma mansoni infection is
      associated with increased HIV prevalence. METHODS: We conducted a household
      survey of residents in island fishing communities in Mukono district, Uganda,
      between October 2012 and July 2013. HIV status was assessed using rapid test
      kits. Kato-Katz (KK) stool tests and urine-circulating cathodic antigen (CCA)
      were used to test for Schistosoma infection. Multivariable logistic regression,
      allowing for the survey design, was used to investigate the association between
      S. mansoni infection and HIV infection. RESULTS: Data from 1412 participants aged
      13 years and older were analysed (mean age 30.3 years, 45% female). The
      prevalence of HIV was 17.3%. Using the stool Kato-Katz technique on a single
      sample, S. mansoni infection was detected in 57.2% (719/1257) of participants;
      urine CCA was positive in 73.8% (478/650) of those tested. S. mansoni infection
      was not associated with HIV infection. [KK (aOR = 1.04; 95% CI: 0.74-1.47, P =
      0.81), CCA (aOR = 1.53; 95% CI: 0.78-3.00, P = 0.19)]. The median S. mansoni egg
      count per gram was lower in the HIV-positive participants (P = 0.005).
      CONCLUSIONS: These results add to the evidence that S. mansoni has little effect
      on HIV transmission, but may influence egg excretion.

PMID- 25976018
TI  - An approach for patient-specific multi-domain vascular mesh generation featuring
      spatially varying wall thickness modeling.
AB  - In this work, we present a computationally efficient image-derived volume mesh
      generation approach for vasculatures that implements spatially varying patient
      specific wall thickness with a novel inward extrusion of the wall surface mesh.
      Multi-domain vascular meshes with arbitrary numbers, locations, and patterns of
      both iliac bifurcations and thrombi can be obtained without the need to specify
      features or landmark points as input. In addition, the mesh output is coordinate
      frame independent and independent of the image grid resolution with high
      dimensional accuracy and mesh quality, devoid of errors typically found in off
      the-shelf image-based model generation workflows. The absence of deformable
      template models or Cartesian grid-based methods enables the present approach to
      be sufficiently robust to handle aneurysmatic geometries with highly irregular
      shapes, arterial branches nearly parallel to the image plane, and variable wall
      thickness. The assessment of the methodology was based on i) estimation of the
      surface reconstruction accuracy, ii) validation of the output mesh using an
      aneurysm phantom, and iii) benchmarking the volume mesh quality against other
      frameworks. For the phantom image dataset (pixel size 0.105 mm; slice spacing 0.7
      mm; and mean wall thickness 1.401+/-0.120 mm), the average wall thickness in the
      mesh was 1.459+/-0.123 mm. The absolute error in average wall thickness was
      0.060+/-0.036 mm, or about 8.6% of the largest image grid spacing (0.7 mm) and
      4.36% of the actual mean wall thickness. Mesh quality metrics and the ability to
      reproduce regional variations of wall thickness were found superior to similar
      alternative frameworks.

PMID- 25976019
TI  - Ultralight boron nitride aerogels via template-assisted chemical vapor
      deposition.
AB  - Boron nitride (BN) aerogels are porous materials with a continuous three
      dimensional network structure. They are attracting increasing attention for a
      wide range of applications. Here, we report the template-assisted synthesis of BN
      aerogels by catalyst-free, low-pressure chemical vapor deposition on graphene
      carbon nanotube composite aerogels using borazine as the B and N sources with a
      relatively low temperature of 900 ( degrees )C. The three-dimensional structure
      of the BN aerogels was achieved through the structural design of carbon aerogel
      templates. The BN aerogels have an ultrahigh specific surface area, ultralow
      density, excellent oil absorbing ability, and high temperature oxidation
      resistance. The specific surface area of BN aerogels can reach up to 1051 m(2) g(
      1), 2-3 times larger than the reported BN aerogels. The mass density can be as
      low as 0.6 mg cm(-3), much lower than that of air. The BN aerogels exhibit high
      hydrophobic properties and can absorb up to 160 times their weight in oil. This
      is much higher than porous BN nanosheets reported previously. The BN aerogels can
      be restored for reuse after oil absorption simply by burning them in air. This is
      because of their high temperature oxidation resistance and suggests broad utility
      as water treatment tools. 

PMID- 25976020
TI  - A field study of lignite as a drying aid in the superheated steam drying of
      anaerobically digested sludge.
AB  - Dried sludge is preferred when the sludge is either to be incinerated or used as
      a soil amendment. This paper focuses on superheated steam drying which has many
      benefits, because the system is totally enclosed, thereby minimising odours and
      particulate emissions. This work reports on field trials at a wastewater
      treatment plant where anaerobically digested sludge is dried immediately after
      being dewatered by belt press. The trials showed that unlike previous off-site
      tests, the sludge could be dried without the addition of a filter aid at a low
      production rate. However, the trials also confirmed that the addition of the
      lignite (brown coal) into the anaerobically digested sludge led to a more
      productive drying process, improved product quality and a greater fraction of the
      product being in the desired product size range. It is concluded that these
      results were achieved because the lignite helped to control the granule size in
      the dryer. Furthermore neither Salmonella spp or E coli were detected in the
      dried samples. Tests on spontaneous combustion show that this risk is increased
      in proportion to the amount of lignite used as a drying aid. 

PMID- 25976021
TI  - Digester performance and microbial community changes in thermophilic and
      mesophilic sequencing batch reactors fed with the fine sieved fraction of
      municipal sewage.
AB  - This study investigates the start-up and operation of bench-scale mesophilic (35 
      degrees C) and thermophilic (55  degrees C) anaerobic sequencing batch reactor
      (SBR) digesters treating the fine sieved fraction (FSF) from raw municipal
      sewage. FSF was sequestered from raw municipal wastewater, in the Netherlands,
      using a rotating belt filter equipped with a 350 micron mesh. For the given
      wastewater, the major component of FSF was toilet paper, which is estimated to be
      10-14 kg per year per average person in the western European countries. A seven
      months adaptation time was allowed for the thermophilic and mesophilic digesters
      in order to adapt to FSF as the sole substrate with varying dry solids content of
      10-25%. Different SBR cycle durations (14, 9 and 2 days) were applied for both
      temperature conditions to study methane production rates, volatile fatty acids
      (VFAs) dynamics, lag phases, as well as changes in microbial communities. The
      prevailing sludge in the two digesters consisted of very different bacterial and
      archaeal communities, with OP9 lineage and Methanothermobacter being pre-dominant
      in the thermophilic digester and Bacteroides and Methanosaeta dominating the
      mesophilic one. Eventually, decreasing the SBR cycle period, thus increasing the
      FSF load, resulted in improved digester performances, particularly with regard to
      the thermophilic digester, i.e. shortened lag phases following the batch
      feedings, and reduced VFA peaks. Over time, the thermophilic digester
      outperformed the mesophilic one with 15% increased volatile solids (VS)
      destruction, irrespective to lower species diversity found at high temperature.

PMID- 25976022
TI  - Influence of late-age births on maternal longevity.
AB  - PURPOSE: To examine the association between the mother's age at last birth and
      maternal long-term survival. METHODS: Data from three national censuses (1972,
      1983, and 1995) and national birth and death records (1972-2009) were used to
      examine the association between age at last birth and mortality while accounting
      for potential confounders, such as parity. Age-adjusted mortality rates and Cox
      proportional hazard models were used in the analysis. RESULTS: A total of 887
      women who delivered their last child after 45 years of age were identified from
      among 178,507 women (1,592,379 person-years). Age-adjusted mortality rates from
      55 years of age were highest for childless women (9.2 per 1000) and decreased
      linearly (P < .001) for parous women with increased age at last birth (5.2 per
      1000 for women aged >=45 years at last birth). In models adjusted for age at
      first birth and parity, mortality risks were lowest among parous women with late
      age births (>=45 years) compared with parous women with their last births before
      35 years of age (hazard ratio, 0.58; 95% confidence interval, 0.40-0.86).
      CONCLUSIONS: This study provides new empirical evidence that late-age births are
      associated with maternal longevity, although a direct causal relation cannot be
      established with the information available.

PMID- 25976023
TI  - The association between disability and intimate partner violence in the United
      States.
AB  - PURPOSE: Prior research has shown that people with disabilities are at greater
      risk of intimate partner violence (IPV) victimization. This study seeks to
      examine the link between disability and IPV in a nationally representative sample
      of U.S. women and men. Also, by establishing that disability preceded recent IPV
      victimization, this study allows for a more thorough understanding of whether
      people with disabilities are at greater risk of victimization subsequent to
      having a disability. METHODS: Data were analyzed from the 2010 National Intimate
      Partner and Sexual Violence Survey, an ongoing, national random digit dial
      telephone survey of U.S. adults. Estimates of age-adjusted 12-month IPV
      prevalence by disability status were calculated. RESULTS: Compared to women
      without a disability, women with a disability were significantly more likely to
      report experiencing each form of IPV measured, which includes rape, sexual
      violence other than rape, physical violence, stalking, psychological aggression,
      and control of reproductive or sexual health. For men, significant associations
      were found with respect to stalking and psychological aggression by an intimate
      partner. CONCLUSIONS: The results suggest that people with a disability are at
      greater risk of victimization and that primary and secondary prevention efforts
      might be targeted to those with a disability.

PMID- 25976025
TI  - Donor attention to reading materials.
AB  - BACKGROUND AND OBJECTIVES: Mandatory predonation reading materials inform donors
      about risk factors for transmissible disease, possible complications of donation
      and changes to the donation process. We aimed to assess the attention to
      predonation reading materials and factors which may affect attention. MATERIALS
      AND METHODS: A national survey in 2008 of 18,108 blood donors asked about self
      assessed attention to reading the materials. In face-to-face interviews, 441
      donors completed additional questions about reading the materials and a literacy
      test. Qualitative interviews of 27 donors assessed their approach to reading.
      RESULTS: In the national survey, most of the first-time donors said they read all
      or most of the materials (90.9% first-time vs. 57.6% repeat donors, P < 0.001)
      and 66% vs. 23.1% reported reading them carefully (P < 0.001). In face-to-face
      interviews comparing those who read materials carefully, skimmed or did not read,
      most knew that donors are informed of positive transmissible disease test results
      (97.1%, 95.5, 98.0 P > 0.05), but fewer recalled seeing the definition of sex
      (77.2%, 56.9, 24.2 P < 0.001). Literacy was poor (30.5% frustration level, 60.3%
      instructional, 9.2% independent) but similar when those who read materials
      carefully, skimmed or did not read were compared (P > 0.05). Qualitative
      interviews showed that donors are reluctant to read any more than necessary and
      decide based on perceived importance or relevance. CONCLUSION: Attention to
      predonation reading materials tends to be better among first-time donors. The
      effectiveness is limited by low motivation to read, especially for repeat donors,
      as well as poor literacy.

PMID- 25976024
TI  - Charting a future for epidemiologic training.
AB  - PURPOSE: To identify macro-level trends that are changing the needs of
      epidemiologic research and practice and to develop and disseminate a set of
      competencies and recommendations for epidemiologic training that will be
      responsive to these changing needs. METHODS: There were three stages to the
      project: (1) assembling of a working group of senior epidemiologists from
      multiple sectors, (2) identifying relevant literature, and (3) conducting key
      informant interviews with 15 experienced epidemiologists. RESULTS: Twelve macro
      trends were identified along with associated actions for the field and
      educational competencies. The macro trends include the following: (1) "Big Data"
      or informatics, (2) the changing health communication environment, (3) the
      Affordable Care Act or health care system reform, (4) shifting demographics, (5)
      globalization, (6) emerging high-throughput technologies (omics), (7) a greater
      focus on accountability, (8) privacy changes, (9) a greater focus on "upstream"
      causes of disease, (10) the emergence of translational sciences, (11) the growing
      centrality of team and transdisciplinary science, and (12) the evolving funding
      environment. CONCLUSIONS: Addressing these issues through curricular change is
      needed to allow the field of epidemiology to more fully reach and sustain its
      full potential to benefit population health and remain a scientific discipline
      that makes critical contributions toward ensuring clinical, social, and
      population health.

PMID- 25976026
TI  - A novel CYLD gene mutation and multiple basal cell carcinomas in a patient with
      Brooke-Spiegler syndrome.

PMID- 25976027
TI  - Frequency of rare recessive mutations in unexplained late onset cerebellar
      ataxia.
AB  - Sporadic late onset cerebellar ataxia is a well-described clinical presentation
      with a broad differential diagnosis that adult neurologists should be familiar
      with. However, despite extensive clinical investigations, an acquired cause is
      identified in only a minority of cases. Thereafter, an underlying genetic basis
      is often considered, even in those without a family history. Here we apply whole
      exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We
      show that 33% of 'idiopathic' cases harbor compound heterozygous mutations in
      known ataxia genes, including genes not included on multi-gene panels, or
      primarily associated with an ataxic presentation.

PMID- 25976028
TI  - Functional neural substrates of posterior cortical atrophy patients.
AB  - Posterior cortical atrophy (PCA) is a neurodegenerative syndrome in which the
      most pronounced pathologic involvement is in the occipito-parietal visual
      regions. Herein, we aimed to better define the cortical reflection of this unique
      syndrome using a thorough battery of behavioral and functional MRI (fMRI) tests.
      Eight PCA patients underwent extensive testing to map their visual deficits.
      Assessments included visual functions associated with lower and higher components
      of the cortical hierarchy, as well as dorsal- and ventral-related cortical
      functions. fMRI was performed on five patients to examine the neuronal substrate
      of their visual functions. The PCA patient cohort exhibited stereopsis, saccadic
      eye movements and higher dorsal stream-related functional impairments, including
      simultant perception, image orientation, figure-from-ground segregation, closure
      and spatial orientation. In accordance with the behavioral findings, fMRI
      revealed intact activation in the ventral visual regions of face and object
      perception while more dorsal aspects of perception, including motion and gestalt
      perception, revealed impaired patterns of activity. In most of the patients,
      there was a lack of activity in the word form area, which is known to be linked
      to reading disorders. Finally, there was evidence of reduced cortical
      representation of the peripheral visual field, corresponding to the behaviorally
      assessed peripheral visual deficit. The findings are discussed in the context of
      networks extending from parietal regions, which mediate navigationally related
      processing, visually guided actions, eye movement control and working memory,
      suggesting that damage to these networks might explain the wide range of deficits
      in PCA patients. 

PMID- 25976029
TI  - Cerebral small vessel disease, cognitive reserve and cognitive dysfunction.
AB  - The concept of cognitive reserve describes differences between individuals in the
      ability to compensate age-related brain changes or pathology as a result of
      greater intellectual enrichment. Cerebral small vessel disease (CSVD) is a common
      age-related vascular disease of the brain associated with slowly accumulating
      tissue damage and represents a leading cause of functional loss, disability and
      cognitive decline in the elderly. The promotion of cognitive reserve might be a
      valuable possibility to moderate the negative impact of accumulating brain
      changes associated with CSVD on cognitive function and thus limit the functional
      consequences of CSVD. We here review existing studies investigating this topic in
      CSVD and provide conceptual considerations why future research is needed.
      Relevant studies were identified using the electronic databases PubMed and
      MEDLINE. Six studies including 7893 subjects were found that all focused on a
      single feature of CSVD only, i.e., white matter hyperintensities (WMH). We also
      included one study investigating 247 CADASIL patients. In general, they confirm
      that higher cognitive reserve (i.e., educational attainment) attenuates the
      negative impact of WMH on cognition. Further studies should attempt to replicate
      this association for all features of CSVD and to expand the concept to other
      areas of functional loss like disordered gait. Finally intervention studies will
      be needed to define when and how we can still increase our cognitive reserve and
      what kind and magnitude of protective effects this may offer.

PMID- 25976030
TI  - A streamlined approach for assessing the Allostatic Load Index in industrial
      employees.
AB  - Work stress is common and can lead to various bodily dysfunctions. The Allostatic
      Load Index (ALI) is a tool to measure the wear and tear of the body caused by
      chronic stress. This cross-sectional study aimed to explore the association of
      work-related stress and ALI in German industrial employees. A short form ALI
      should be developed for practical use of company physicians. In this exploration
      of an industrial cohort (n = 3797; 79.3% male), work stress was measured by the
      effort-reward imbalance (ERI) questionnaire in 2009-2011. ALI was calculated
      using 15 variables including anthropometric data, heart rate variability, as well
      as blood and urine samples based on predefined subclinical cut-off values.
      Differences in ALI related to low (<=1) and high (>1) ERI categories were tested.
      Logistic regression models estimated odds ratios (ORs) and corresponding 95%
      confidence intervals (CIs) for the association between ALI and work stress
      controlling for multiple confounders. Employees exposed to high work stress
      showed higher ALI scores (p < 0.001) compared to those with low stress levels. In
      multivariable models, ALI was associated with work stress (OR 1.19 [95% CI: 1.00,
      1.42]; p < 0.05) following adjustment for a range of potential confounders. By
      reducing ALI parameters to five variables this association increased modestly and
      remained statistically significant (OR 1.27 [95% CI: 1.05, 1.54]; p < 0.05). The
      results indicate that work stress is associated with ALI in German industrial
      employees. A short form index seems to be a promising approach for occupational
      health practitioners. The results should be validated in further longitudinal
      explorations defining a standard set of variables including gender-related
      thresholds. 

PMID- 25976031
TI  - Multilocus sequence analysis reveals taxonomic differences among Bradyrhizobium
      sp. symbionts of Lupinus albescens plants growing in arenized and non-arenized
      areas.
AB  - Lupinus albescens is a leguminous plant that belongs to "New World" lupine
      species, which is native to southern Brazil. This Brazilian region is
      characterized by poor degraded soils with low organic matter and is designated as
      an arenized area. The symbiosis between Lupinus plants and nitrogen-fixing
      bacteria belonging to the Bradyrhizobium genus may help the plant establish
      itself in these areas. To characterize the bradyrhizobial population symbionts of
      L. albescens plants grown in arenized and non-arenized areas, a multilocus
      phylogenetic analysis allied to genetic diversity indices were conducted. Seventy
      four bradyrhizobial isolates were analyzed, 38 coming from L. albescens plants
      growing in an arenized area and 36 from a non-arenized area. Isolates were
      different between arenized and non-arenized areas. Phylogenetic analysis of the
      16S rRNA, dnaK, atpD, recA, glnII, rpoB, gyrB, nodA, nodB, and nodZ genes
      resulted in three supported clades, which were most likely to be three different
      new Bradyrhizobium species: one species from the arenized area and two from the
      non-arenized area. Estimates of genetic diversity, which decreased in arenized
      areas, were positively correlated with habitat variability. These results
      suggested that a few resistant and efficient Bradyrhizobium sp. strains were
      capable of forming nodules on L. albescens plants growing in an arenized area. An
      in vivo inoculation experiment with L. albescens plants showed that
      Bradyrhizobium ssp. isolated from this extreme environment were more efficient at
      promoting plant growth than those from the non-arenized area. This result
      suggested that the environment affected the selection of more efficient plant
      growth promoters in order to sustain plant growth.

PMID- 25976032
TI  - Spatially uniform but temporally variable bacterioplankton in a semi-enclosed
      coastal area.
AB  - Studies focusing on the temporal and spatial dynamics of bacterioplankton
      communities within littoral areas undergoing direct influences from the coast are
      quite limited. In addition, they are more complicated to resolve compared to
      communities in the open ocean. In order to elucidate the effects of spatial vs.
      temporal variability on bacterial communities in a highly land-influenced semi
      enclosed gulf, surface bacterioplankton communities from five coastal sites in
      Igoumenitsa Gulf (Ionian Sea, Greece) were analyzed over a nine-month period
      using 16S rDNA 454-pyrosequencing. Temporal differences were more pronounced than
      spatial ones, with lower diversity indices observed during the summer months.
      During winter and early spring, bacterial communities were dominated by SAR11
      representatives, while this pattern changed in May when they were abruptly
      replaced by members of Flavobacteriales, Pseudomonadales, and Alteromonadales.
      Additionally, correlation analysis showed high negative correlations between the
      presence of SAR11 OTUs in relation to temperature and sunlight that might have
      driven, directly or indirectly, the disappearance of these OTUs in the summer
      months. The dominance of SAR11 during the winter months further supported the
      global distribution of the clade, not only in the open-sea, but also in coastal
      systems. This study revealed that specific bacteria exhibited distinct succession
      patterns in an anthropogenic-impacted coastal system. The major bacterioplankton
      component was represented by commonly found marine bacteria exhibiting seasonal
      dynamics, while freshwater and terrestrial-related phylotypes were absent. 

PMID- 25976034
TI  - Early regimes of water capillary flow in slit silica nanochannels.
AB  - Molecular dynamics simulations are conducted to investigate the initial stages of
      spontaneous imbibition of water in slit silica nanochannels surrounded by air. An
      analysis is performed for the effects of nanoscopic confinement, initial
      conditions of liquid uptake and air pressurization on the dynamics of capillary
      filling. The results indicate that the nanoscale imbibition process is divided
      into three main flow regimes: an initial regime where the capillary force is
      balanced only by the inertial drag and characterized by a constant velocity and a
      plug flow profile. In this regime, the meniscus formation process plays a central
      role in the imbibition rate. Thereafter, a transitional regime takes place, in
      which, the force balance has significant contributions from both inertia and
      viscous friction. Subsequently, a regime wherein viscous forces dominate the
      capillary force balance is attained. Flow velocity profiles identify the passage
      from an inviscid flow to a developing Poiseuille flow. Gas density profiles ahead
      of the capillary front indicate a transient accumulation of air on the advancing
      meniscus. Furthermore, slower capillary filling rates computed for higher air
      pressures reveal a significant retarding effect of the gas displaced by the
      advancing meniscus. 

PMID- 25976033
TI  - Nonspecific labeling limits the utility of Cre-Lox bred CST-YFP mice for studies
      of corticospinal tract regeneration.
AB  - Studies of axon regeneration in the spinal cord often assess regeneration of the
      corticospinal tract (CST). Emx1-Cre x Thy1-STOP-YFP mice have been reported to
      have yellow fluorescent protein (YFP) selectively expressed in forebrain neurons
      leading to genetic labeling of CST axons in the spinal cord, and it was suggested
      that these CST-YFP mice would be useful for studies of CST regeneration. Because
      regeneration past a lesion may involve only a few axons, the presence of labeled
      non-CST axons compromises interpretation. We show here that in CST-YFP mice, some
      YFP-labeled axons are not from the CST. Specifically, YFP-labeled axons are
      present in regions beyond those with anterogradely labeled CST axons, most YFP
      labeled axons beyond established CST locations do not undergo Wallerian
      degeneration following a large lesion of the sensorimotor cortex, some
      rubrospinal and reticulospinal neurons are labeled with YFP, and some YFP-labeled
      cells in the spinal gray matter have YFP-labeled projections into the spinal cord
      white matter. We further demonstrate that the density of YFP-labeled axon arbors
      hinders tracing of single axons to their point of origin in the main descending
      tracts. In light of recent advances in 3D imaging for visualizing axons in
      unsectioned blocks of spinal cord, we also assessed CST-YFP mice for 3D imaging
      and found that YFP fluorescence in CST-YFP mice is faint for clearing-based 3D
      imaging in comparison with fluorescence in Thy1-YFP-H mice and fluorescence of
      mini-ruby biotinylated dextran amine (BDA). Overall, the nonspecific and faint
      YFP labeling in CST-YFP mice limits their utility for assessments of CST axon
      regeneration.

PMID- 25976035
TI  - Endocultivation: Histomorphological effects of repetitive rhBMP-2 application
      into prefabricated hydroxyapatite scaffolds at extraskeletal sites.
AB  - The timing of application of recombinant human bone morphogenic protein-2 (rhBMP
      2) may be important in determining the final outcome of engineered bone tissue.
      This study investigates the impact of repetitive rhBMP-2 application on hard and
      soft tissue morphology in endocultivation. A 3D-printed scaffold was implanted
      into a pouch in the latissimus dorsi muscle in 40 Lewis rats. RhBMP-2 was
      injected at defined time points and animals received a total of 200 MUg each.
      Control groups received either rhBMP-2 simultaneously with scaffold implantation,
      or solely a scaffold with no rhBMP-2. Fluorescence markers were injected after
      operation. CT-scans and histological examination were performed after 8 weeks.
      Multiple comparisons revealed significant differences of bone density between the
      groups who received delayed injections at two separate time points in time
      compared to those who had simultaneous rhBMP-2 application (p = 0.0038; p =
      0.0063) and the control group (p = 0.017, p = 0.0284). The blood vessel count was
      significantly higher in groups with repetitive injections compared with both
      control groups. Two soft tissue types were identified and found to have different
      distributions in the different study groups. Fluorescence labeling showed active
      new bone formation after 4-5 weeks in all groups where rhBMP-2 was administered.
      Multiple repetitive injections were more effective than simultaneous application
      regarding bone density indicating time-dependent effects of rhBMP-2. Bone
      formation processes were detectable several weeks after rhBMP-2 application
      indicating long-term effects.

PMID- 25976036
TI  - Reducing cone beam CT scan height as a method of radiation reduction for
      photorealistic three-dimensional orthognathic planning.
AB  - OBJECTIVES: To determine the superimposition accuracy of full-face
      stereophotographic images with 22 cm and 13 cm cone beam computed tomography
      (CBCT) scans. MATERIAL AND METHODS: 22 cm CBCT scans and corresponding
      stereophotographic images (3 dMD) for 30 subjects requiring orthognathic surgery
      were randomly selected. A 13 cm CBCT scan was generated from the 22 cm scan for
      each subject. All scans and images were converted into STL format. For each
      subject, the 22 cm and 13 cm CBCT scans were imported into CAD/CAM software and
      each superimposed with the corresponding 3 dMD image. A one-sample t-test was
      used to test the null hypothesis that the difference in the 90th percentile of
      the mean absolute distance between the two 3dMD images when aligned on the 22 cm
      and the 13 cm CBCT scans was not clinically significant (<0.5 mm). RESULTS: The
      90th percentile of the mean absolute distance between the two 3 dMD surfaces
      using the 22 cm and 13 cm CBCT scans was significantly less than 0.5 mm (p <
      0.001; 0.2 +/- 0.2 mm; 95% CI, 0.16-0.30 mm). CONCLUSIONS: There is no difference
      in the accuracy of superimposition of a stereophotogrammetry image with a 22 cm
      CBCT scan or a 13 cm CBCT scan. It should now be possible to use a 13 cm CBCT
      scan and a full-face stereophotogrammetry image during 3D orthognathic planning
      to reduce radiation exposure.

PMID- 25976037
TI  - Early two-stage repair of clefts in holoprosencephaly.
AB  - Holoprosencephaly (HPE) presents with a spectrum of severity, but in its totality
      is the most common malformation of the embryonic forebrain occurring 1 in 10,000
      to 1 in 20,000 live births. Due to the poor prognosis, treatment of mid-face
      clefts in HPE patients have classically been addressed in a delayed fashion after
      1-year of age. Improvements in the ability to manage medical complications
      associated with HPE along with an increased understanding and lower mortality
      rates in less severe forms have challenged these previous practiced routines.
      Accompanied by advances in understanding of HPE and identification of genes
      responsible for sporadic forms, we are able to better guide timing of surgical
      intervention. We present a patient with lobar HPE and a type IV facial deformity
      treated with early repair of the median facial cleft. We believe this treatment
      strategy was safe, given her relatively good prognosis. We propose that patients
      with HPE displaying less severe neural non-cleavage may be good candidates for
      earlier two-stage intervention. SUMMARY: The historically poor prognosis of
      patients with holoprosencephaly (HPE) has led to midline facial clefts have being
      addressed in a delayed fashion after 1-year of age. Improvements in the ability
      to manage medical complications associated with HPE and lower mortality rates in
      less severe forms have challenged these previous practiced routines.
      Additionally, the identification of genes responsible for sporadic forms of HPE
      can better guide timing of surgical intervention and improve developmental
      outcomes. We present a patient with lobar HPE and a type IV facial deformity
      treated with an early two-stage repair of the median facial cleft. We propose
      patients with HPE displaying less severe neural non-cleavage may be good
      candidates for earlier intervention.

PMID- 25976038
TI  - Changes in nose symmetry in unilateral cleft lip and palate treated by differing
      pre-surgical assistance: An objective assessment of primary repair.
AB  - BACKGROUND: Residual deformity of the nose, not lip, continues to be the greater
      challenge in UCCLP rehabilitation. Platform distortions often re-emerge following
      primary reconstruction revealing the stereotypical cleft-nose. Nasal alveolar
      molding reduces nose asymmetry. However, this study applies directional mechanics
      to the underlying platform distortions and soft tissue nose, introducing a novel
      device addressing the distorted septo-premaxillary junction. METHODS:
      Retrospective assessment of 47 UCCLP patients by 2-dimensional photographic
      analysis with 24 subjects treated by dento-maxillary advancement (DMA) and nasal
      septum button-head pin (NSBP), 17 having nasal molding (NM), compared to 23
      subjects without nose treatment, 16 with DMA and 7 with passive plates.
      Measurements were assessed by t tests, <= 05 confidence. RESULTS: Frontal view:
      nose-treatment sample achieved ideal ala-bases vertical symmetry (p = 0.00065 &
      0.00073); significantly improved ala-rims "slump" angle (p = 0.0071). Both
      samples had nose positioning within the facial frame like non-cleft population.
      Sub-nasal view: significant differences were for columella angle (p = 0.0015),
      nares "offset" (p = 0.002), and columella symmetry (p = 0.022) with nose
      treatment achieving near ideal columella symmetry score (0.92) vs. (0.81).
      CONCLUSIONS: NM and the novel NSBP procedures integrated with the platform
      correction effect of the DMA successfully treated at three distorted anatomic
      levels native to UCCLP to improve nasal aesthetics.

PMID- 25976039
TI  - Differential expression of TLR3 and TLR4 in keratocystic odontogenic tumor
      (KCOT): A comparative immunohistochemical study in primary, recurrent, and nevoid
      basal cell carcinoma syndrome (NBCCS)--associated lesions.
AB  - BACKGROUND: Toll-like receptors (TLRs) play an essential role in the activation
      of innate immunity and they can promote cancer cell survival and tumor
      progression. It has been claimed that TLRs can somehow predict the clinical
      behavior in oral squamous cell carcinoma (OSCCs). AIM: To elucidate the molecular
      basis underlying keratocystic odontogenic tumor (KOCTs) aggressive behavior and
      recurrence we carried out this immunohistochemical study on TLR3 and TLR4
      expression in sporadic primary KCOTs (sp-KCOTs), sporadic recurrent KCOTs (sp
      KCOTs), and NBCCS-associated KCOTs (NBCCS-KCOTs). METHOD: 40 cases of KOCTs
      removed from 23 men and 17 women were the sample. Paraffin-embedded blocks were
      processed for immunohistochemistry. Sections were incubated with TLR3 and TLR4
      antibodies and immunoreactivity evaluated on a semi-quantitative score. RESULTS:
      Both TLR3 and TLR4 were expressed in KCOTs epithelium, although with a different
      extent. TLR3 was not expressed in sp-KCOTs and sr-KCOTs, but it showed a faint
      staining in NBCCS-KCOTs. On the other hand, both cytoplasmic and nuclear staining
      for TLR4 was detected in all the 3 types of lesions; however being significantly
      more expressed in sr-KCOT and NBCCS-KCOTs (p < 0.0001). Our results, demonstrated
      an association between TLR4, but not TLR3 expression to recurrence behavior of
      KCOTs. In fact, TLR4 was up-regulated in sr-KCOTs and NBCCS-KCOTs but not in sp
      KCOTs. CONCLUSIONS: According these findings it seems conceivable to assume that
      the up-regulation of TLR4 in some KCOTs can be correlated somehow to their
      tendency recurrence.

PMID- 25976040
TI  - Personalised pharmacotherapy: an interim solution for antidepressant treatment?

PMID- 25976041
TI  - Tetralogy of Fallot with Morgagni's Hernia.

PMID- 25976042
TI  - [Early inadequate antibiotic therapy vs multi-drug resistant organisms infection
      in ICU].

PMID- 25976043
TI  - [Appropriate anti-infection therapy in severe sepsis and septic shock: How to
      walk out of the clinical confused zone].

PMID- 25976044
TI  - [Epidemiological characteristics and risk factors for patients with catheter
      related bloodstream infections in intensive care unit].
AB  - OBJECTIVE: To explore the epidemiological characteristics, bacterial composition
      and risk factors for patients with catheter-related bloodstream infection (CRBSI)
      in intensive care unit (ICU). METHODS: A prospective survey was conduced for 2
      605 ICU patients during January 2010 to December 2013. The clinical data of CRBSI
      and non-CRBSI patients were compared and their relevant risk factors analyzed.
      RESULTS: Among them, there were 1 773 cases of arteriovenous catheterization. And
      94 cases (5.3%) had CRBSI. The 1 000-day catheter infection rate was 9.8. The
      mortality rates of CRBSI and non-CRBSI patients were 23.4% and 10.7%
      respectively. And the difference was statistically significant (chi2 = 14.38, P <
      0.01). The occurrence of CRBSI was a risk factor for mortality. Logistic
      regression analysis showed that the occurrence of CRBSI was 3.33 folds for venous
      catheterization time > 6 days over <= 6 days (95% CI: 2.04-5.56), 2.50 folds for
      trauma patients over non-trauma ones (95% CI: 1.49-4.17), 2.98 folds for
      malignant tumors patients over non-malignant tumors ones (95% CI: 1.61-5.51) and
      4.32 folds for diabetics over non-diabetics (95% CI: 2.07-9.01). For different
      sites of arteriovenous catheterization, the occurrences of CRBSI were not
      statistically significant. For CRBSI patients with blood culture, the positive
      microorganisms were gram-negative bacteria (61.7%), gram-positive bacteria (26%)
      and fungi (12.3%). CONCLUSION: The occurrence of CRBSI is a risk factor for
      mortality. And diabetes, trauma and arteriovenous catheterization time > 6 days
      are risk factors for CRBSI. Comprehensive preventive measures should be taken to
      reduce the incidence of CRBSI.

PMID- 25976045
TI  - [Species distribution of pathogens and prognostic factors for catheter-related
      bloodstream infections in intensive care unit].
AB  - OBJECTIVE: To explore the incidence and species distribution of catheter-related
      bloodstream infection (CRBSI) in intensive care unit (ICU) at our hospital and
      analyze the risk factors for CRBSI. METHODS: Hospitalized patients
      microbiologically diagnosed as CRBSI were recruited from January 2012 to June
      2013. And the clinical data were collected retrospectively and analyzed by
      software IBM SPSS 19.0. RESULTS: Among 67 patients diagnosed as nosocomial CRBSI,
      24 cases (35.8%) died while 43 survived. And a total of 81 strains were detected,
      including 42 Gram-positive (G+) bacteria (51.9%), 36 Gram-negative (G-) bacteria
      (44.4%) and 3 fungi (3.7%).The predominant pathogenic G+ and G- bacteria were
      Staphylococcus epidermidis and Acinetobacter baumannii respectively. With
      multiple Logistic regressions, age >= 65 years, higher acute physiology & chronic
      health evaluation II (APACHE II) score and polymicrobial CRBSI were independent
      predictors of worse outcomes. CONCLUSION: The recent prevalent pathogens of CRBSI
      in ICU are S.epidermidis and A.baumannii. Advanced age, disease severity and
      polymicrobial CRBSI are significant independent risk factor of mortality for
      CRBSI patients in ICU.

PMID- 25976046
TI  - [Effects of target blood glucose control with insulin therapy on systolic and
      diastolic cardiac function in septic patients].
AB  - OBJECTIVE: To explore the protective effects of target blood glucose control on
      cardiac dysfunction in septic patients. METHODS: For this prospective and
      randomized interventional study, a total of 90 septic patients were divided into
      group A (blood glucose levels of 4.4 to 6.1 mmol/L), group B (6.1 to 8.3 mmol/L)
      and group C (8.3 to 10.0 mmol/L) (n = 30 each). And 30 non-septic subjects were
      selected into control group. Serial transthoracic echocardiogram (TTEs) was
      performed to measure left ventricle ejection fraction (LVEF) and ratio of blood
      flow velocity of mitral annulus during early diastole (E) and atrial contraction
      (A) before and 1, 3, 7 days after blood glucose control with insulin therapy. The
      plasma level of brain natriuretic peptide (BNP) was detected by enzyme-linked
      immunosorbent assay (ELISA). The patient records were reviewed to obtain
      information about demographics, Acute Physiology and Chronic Health Evaluation II
      (APACHE II) scores, incidence of hypoglycemia and 28-days survival rates.
      RESULTS: No significant inter-group improvement existed in mean values of LVEFs
      (P = 0.184). And E/As differed among the groups and there was statistical
      difference between groups A and C (P = 0.005). There was a increasing trend for
      the levels of BNP of groups A, B and C. And comparison of group A with group B/C
      had statistical variability (PAB = 0.028, P(Ac) = 0.000). LVEFs had no variation
      (P1= 0.310, P3= 0.174) while E/A and BNP were significantly higher or lower in
      group A than those in others at Day 1 and 3 (P = 0.005). The LVEFs were similar
      at Day 7 and E/As and BNPs of groups A, B and C showed statistical differences.
      The variation of E/As with time differed between groups A, B and C. CONCLUSION:
      Maintaining a target blood glucose of 4.4 to 6.1 mmol/L may improve cardiac
      dysfunction. Furthermore, it has more significant improvement of diastolic
      dysfunction than systolic counterpart. Combined utilization of LVEF, E/A and BNP
      is better in evaluating critical ill patients with sepsis-induced cardiomyopathy
      under target blood glucose control. It suggests that a glucose level of 4.4 to
      6.1 mmol/L may benefit cardiac consistent dysfunction in septic patients during 7
      days after treatment.

PMID- 25976047
TI  - [Serum uric acid level and clinical relevance analysis in autoimmune myelopathy].
AB  - OBJECTIVE: To quantify serum uric acid (UA) levels in autoimmune myelopathy (AMs)
      patients and analyze the clinical relevance. METHODS: Blood samples from
      hospitalized patients with AMs (n = 69) in acute phase and other neurological
      disorders (n = 50) between September 2009 and December 2013 and healthy subjects
      (n = 50) were used to detect UA level by enzymatic calorimetric method.Expanded
      disability status scale (EDSS) and spinal MRI-T2 imaging were used for clinical
      and imaging severity evaluations.And serum AQP4 anitbody and other antibodies
      were tested. RESULTS: Serum UA level in AMs patients ((223 +/- 76) umol/L) was
      lower than in controls ((325 +/- 53) umol/L and (324 +/- 48) umol/L, P < 0.001);
      for clinical relevance analysis, serum UA levels in females ((208 +/- 64)
      umol/L), age >= 40 years ((185 +/- 64) umol/L), EDSS score >= 4.5 ((179 +/- 59)
      umol/L), transverse lesion ((179 +/- 56) umol/L) and neuromyelitis
      optica/spectrum disorders ((199 +/- 70) umol/L) were lower than in males ((252 +/
      88) umol/L, P < 0.05), age < 40 years ((266 +/- 66) umol/L, P < 0.001), EDSS
      score < 4.5 ((257 +/- 70) umol/L, P < 0.001), non-transverse lesion ((274 +/- 64)
      umol/L, P < 0.001) and multiple sclerosis ((261 +/- 69) umol/L, P < 0.05). An
      inverse correlation existed between UA level and involved spinal segments (r = 
      0.665, P < 0.001); status of serum antibodies and associated diseases showed no
      significant differences. CONCLUSION: Serum UA level is low and shows strong
      relevance with clinical and imaging severity in AMs patients. And UA is
      recommended as a biomarker of AMs.

PMID- 25976048
TI  - [Magnetic resonance spectroscopy in lenticular nucleus of Bipolar II disorder and
      its relation with cognitive function].
AB  - OBJECTIVE: To explore the magnetic resonance spectroscopy characteristics of
      lenticular nucleus in Bipolar II disorder and its relation with cognitive
      function. METHODS: Thirty Bipolar II disorder patients in hospital from 2012
      September to 2013 April and twenty healthy controls were evaluated with Multi
      Voxel 1H-MRS scans on lenticular nucleus to assess the NAA, Cho, Cr and MI. All
      subjects were assessed for attention using the Stroop Test and executive function
      by Wisconsin card sorting test. RESULTS: NAA, Cho, Cr in right lenticular nucleus
      and Cr in left lenticular nucleus were lower than healthy controls (P < 0.05).
      The patients showed significant cognitive impairment in all aspects of Stroop
      Test and Wisconsin card sorting test (P < 0.05). NAA in right lenticular nucleus
      was positively correlated with correct number of Stroop-CW. CONCLUSIONS: Neural
      dysfunction in right lenticular nucleus of Bipolar II disorder may influence
      attention function. Cellular energy metabolism rate was reduced in bilateral
      lenticular nucleus.

PMID- 25976049
TI  - [Clinical analyses of surgical treatment for lung metastatic tumors].
AB  - OBJECTIVE: To evaluate the distribution, diagnosis, indication and modus operandi
      of surgical treatment and prognostic factors for patients with lung metastatic
      tumors. METHODS: The clinical features were collected for 329 surgical patients
      with lung metastatic tumors during March 1998 and December 2013. Survival
      analysis was also performed by Log-rank test and Cox-regression analysis.
      RESULTS: The origins were epithelial tissue tumors (n = 278), sarcomas (n = 32),
      germ cell tumors (n = 3), malignant melanoma (n = 3) and miscellaneous tumors (n
      = 13). Their 1, 3 and 5-year survival rates were 85.1%, 50.9% and 37.1%
      respectively with a median survival time of 38 months. Log-rank survival analysis
      showed that resection extent (P = 0.004), lymph node dissection (P = 0.017) and
      radical operation (P < 0.01) were significantly associated with patient survival.
      And multi-variable Cox-regression analysis showed that lymph node dissection and
      radical operation were two independent prognostic factors. CONCLUSION: For lung
      metastatic tumor patients with well-controlled primary malignancy and non
      metastasis of other organs, radical resection should be performed with minimal
      resection extent. And routine systematic lymph node dissection is not
      recommended. The necessity of lymph node dissection should be determined by
      radiological evaluations and surgical explorations.

PMID- 25976050
TI  - [Analyses of 77 patients with hemophagocytic syndrome].
AB  - OBJECTIVE: To summarize the clinical features and laboratory data of 77 patients
      with hemophagocytic syndrome (HPS). METHODS: A total of 77 patients of HPS were
      continuously collected from 2007 to 2014 at our hospital. Their underlying
      diseases, clinical features, laboratory data, therapy and prognosis were
      analyzed. RESULTS: Their The patients aged from 3 months to 85 years. The gender
      ratio was roughly equal. Primary HPS was diagnosed in only 5 cases by gene
      detection Another 72 cases belonged to secondary HPS. The causes were infection
      (n = 28), hematologic neoplasm (n = 25), autoimmune diseases (AID, n = 11) and
      unknown (n = 8). HPS was the initial symptom in nearly half cases of hematologic
      neoplasm and AID. HPS was characterized by high fever (100%), hypersplenomegaly
      (81.8%) and lymphadenopathy (40.3%). Laboratory data showed cytopenia (94.8%),
      serum ferritin elevation (93.2%), hypofibrinogenemia (61.8%), hemophagocytosis in
      bone marrow (78.1%) and hypertriglyceridemia (55.3%). Low NK-cell activity
      (95.2%) and elevation of sCD25 (100%) were specific manifestations in HPS.
      Pulmonary infection (36.4%) and hepatic malfunction (33.3%) were common.
      Approximately 70% were treated with HLH-2004. Pulse-dose corticosteroid therapy
      (methylprdnisolone 200-500 mg/d) was used in 8 AID patients. And 14 patients died
      and 10 withdrew treatment because of exacerbation. Five had complications of DIC
      and another 5 progressed into MODS. Neoplasm (52.0%) had the highest mortality in
      secondary HPS. And infection (25.0%) and AID (18.2%) followed. CONCLUSION:
      Sometimes HPS occurs simultaneously with autoimmune disease or neoplasm. Relevant
      laboratory tests for suspected patients may aid an early diagnosis. Presence of
      DIC or MODS in HPS is possibly correlated with a poor prognosis and a high
      mortality.

PMID- 25976051
TI  - [Relationship between endometriosis stage, characteristics of enodmetriotic
      lesions and severity of dysmenorrhoea].
AB  - OBJECTIVE: To explore the association between endometriosis stage,
      characteristics of endometriotic lesions and severity of dysmenorrhoea. METHODS:
      The clinical data were collected from 140 patients with laparoscopically
      diagnosed endometriosis between May 2013 and December 2013. They were scored by
      visual analogue scale (VAS) according to their preoperative dysmenorrhoea.
      Endometriotic lesions were recorded by their anatomical distributions. And
      endometriosis was staged and scored according to the score of Revised American
      Fertility Society (r-AFS). The relationship between dysmenorrhoea and
      endometriosis stage as well as endometriotic foci was analyzed. Chi-square test
      and Logistic regression were used for statistical analyses. RESULTS: Among them,
      there were 95 (67.86%) patients with dysmenorrhoea and 45(32.14%) without
      dysmenorrhoea. No significant inter-group difference existed in age (P > 0.05).
      The interval from menarche to the onset of dysmenorrhoea was (8 +/- 9) years and
      duration of dysmenorrhoea (2.3 +/- 1.5) days each month. A correlation existed
      between endometriosis stage and severity of dysmenorrhoea (chi2 = 20.677, P <
      0.05). A strong association was found between posterior cul-de-sac obliteration
      and severity of dysmenorrhoea (chi2 = 8.471, P < 0.05). No significant difference
      was found for ovarian endometriomas, ovarian adhesion, superficial peritoneal
      lesions and deep infiltrating endometriosis in non- and minimal dysmenorrhoea
      groups with moderate and severe dysmenorrhoea (P > 0.05). Posterior cul-de-sac
      obliteration was an independent influencing factor for dysmenorrhoea. The odds
      ratio (OR) was 3.291 and 95% confidence interval (CI) 1.453-7.454. However, no
      relevance existed between ovarian endometriomas and dysmenorrhoea by Logistic
      analysis. CONCLUSION: The severity of dysmenorrhoea has close correlation with
      posterior cul-de-sac obliteration. However, there is a weak relevance with
      ovarian endometreaiomas.

PMID- 25976052
TI  - [Assessments setup errors and target margin by 6D couch for primary cervical
      cancer].
AB  - OBJECTIVE: To explore the inter and intra-fractional setup variations of HexaPOD
      evo RT 6-degree-of-freedom treatment couch plus kilovoltage (KV) cone-beam
      computed tomography (CBCT) in patients with primary cervical cancer and calculate
      the proper margins of CTV for clinical use. METHODS: From May 2013 to April 2014,
      16 consecutive patients with primary cervical cancer were enrolled. Elekta
      AXESSETM image guided radiation therapy (IGRT) modalities and vacuum pad were
      employed. All patents were treated in a prone position after Lac light
      correction. Then daily CBCT scans prior to were performed treatment delivery,
      another CBCT scan after 6D couch online correction and a third one after each
      treatment. After automatic registration to planning CT, three translational X, Y,
      Z and three rotational Rx, Ry, Rz shifts were analyzed for intra and inter
      fraction assessments and CTV margins. RESULTS: CBCT plus 6D couch could reduce
      the inter-fraction errors of X (t = 3.87, P = 0.000), Z (t = -7.92, P = 0.000),
      Rx (t = 3.05, P = 0.003), Ry (t = -6.87, P = 0.000) statistically and Ry was
      significantly different between pre and post-treatment (t = 3.242, P = 0.002). As
      to intra-fraction variations, the CTV margins were 2.74 mm, 3.9 mm and 2.87 mm on
      X, Y and Z directions respectively. CONCLUSION: Corrections with CBCT and HexaPOD
      evo RT 6D may considerably reduce the translational and rotational setup
      variations and gain lower PTV volume for intact cervical cancer. Thus it protects
      normal tissues better and improves the accuracy of high-precision treatments.

PMID- 25976053
TI  - [Validity of high intensive focused ultrasound in the treatment of uterus myoma
      and adenomyoma in Hebei Province: a report of 166 cases].
AB  - OBJECTIVE: To explore the validity of high intensive focused ultrasound (HIFU) in
      the treatment of uterus myoma and adenomyoma. METHODS: A total of 166 patients
      with uterus myoma and adenomyoma received HIFU treatment from July 2011 to
      November 2013 at our hospital. The follow-ups were conducted at 1, 3, 6 month
      post-treatment. Their status of clinical symptoms, tumor volume, blood flow and
      efficacy of HIFU were evaluated. RESULTS: Menstrual blood decreased after
      treatment. The levels of hemoglobin all returned to normal in anemic patients and
      dysmenorrhea showed great improvement. Ultrasound showed that uterine ablation
      lesions significantly diminished after treatment. The effective rate was 71.8% at
      1 month, 86.1% at 3 month and 95.4% at 6 month post-treatment and blood flow
      within ablation lesions decreased after treatment. None of unacceptable side
      effects occurred. CONCLUSION: HIFU treatment of uterus myoma and adenomyoma is
      both feasible and safe with fewer side effects.

PMID- 25976054
TI  - [Regulatory mechanisms of interleukin-1beta on the cyclooxygenase-2 system
      expression of human neuroglioma cells].
AB  - OBJECTIVE: To explore the molecular mechanisms by which interleukin-1beta (IL
      1beta) regulates the expression of cytosolic phospholipase A2 (cPLA2) and
      cyclooxygenase-2 (COX-2) in human neuroglioma cell. METHODS: H4 neuroglioma cells
      were treated with IL-1beta (2.5 ug/L) for different timepoints up to 72 h. For
      MAPK study, cells were incubated for 1 h with MAPK inhibitors, SB203580 and
      PD98059 and subsequently stimulated with IL-1beta (1 ug/L) for 24 h. Northern and
      Western blot were used to determine the protein expressions of cPLA2 and COX-2
      respectively. And the content of PGE2 in supernatant was determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: A dose of 2.5 ug/L IL-1beta induced
      the protein expressions of cPLA2 and COX-2 and a subsequent release of PGE2 in a
      time-dependent manner. And the expressions of cPLA2 and COX-2 peaked at 24 h
      after stimulation (P < 0.05). The expression of PGE2 increased 250 folds after a
      72 h culture. Both SB203580 and PD98059 inhibitors reduced IL-1beta-induced PGE2
      production while SB203580 alone reduced the expressions of both cPLA2 and COX-2.
      CONCLUSION: IL-1beta induces the expressions of cPLA2 and COX-2 and affects COX-2
      at the post-translational level by modulating PGE2 production through the signal
      transduction pathways of p38 and p42/44 MAPKs.

PMID- 25976055
TI  - [Clinical epidemiological study of peri-conceptional multiple risk factors and
      congenital heart diseases].
AB  - OBJECTIVE: To evaluate the associations between the occurrence of congenital
      heart diseases (CHDs) in children and exposures to peri-conceptional multiple
      nongenetic risk factors. METHODS: For this age-matched case-control study,
      standardized data were collected from 435 families of children with CHD and 574
      families of non-malformed children. The questionnaires were conducted on multiple
      nongenetic risk factors including paternal characteristics and conditions,
      maternal therapeutic drug exposure, housing renovation, hair perming and dyeing
      and parental occupational exposure. RESULTS: The CHD infants weighed less than
      control group (P < 0.01). However two groups had no significant differences in
      age, height, parental age or heart rate. Educational levels of parents had a
      negative correlation with CHD. Conotruncal defect and simple ventricular septum
      defect were the most common cardiac abnormalities. Therapeutic drug exposure,
      viral infection and occupational exposure all had a high level of correlation
      with conotruncal defect (OR = 6.74, OR = 3.73, OR = 2.82 respectively). And
      ventricular septum defect was associated with therapeutic drug exposure, home
      decoration, hair perming and dyeing and parental exposure of work environment (OR
      = 2.77, OR = 1.76, OR = 1.89 respectively). CONCLUSION: Multiple nongenetic risk
      factors may contribute to the occurrence of CHD.

PMID- 25976056
TI  - Health economic models in hemophilia A and utility assumptions from a clinician's
      perspective.
AB  - BACKGROUND: The clinical benefits of prophylaxis in patients with hemophilia are
      well-established and include the following: reduced bleeding episodes, prevention
      of joint damage, decreased inhibitor development, and improved health-related
      quality of life. However, the cost-effectiveness of prophylaxis is still not
      clear. PROCEDURES: We reviewed the published hemophilia prophylaxis economic
      models focusing on utility assumptions. RESULTS: We found six cost-utility
      studies that compared prophylaxis and on-demand regimens. These studies reported
      remarkably different results, using utility values based on different assumptions
      and data sources. CONCLUSIONS: We suggest that cooperation among key stakeholders
      (clinicians, patient organizations and health-care decision makers) as a means of
      collecting evidence-based and experiential data to represent both the utility and
      the quality of life changes for patients with Hemophilia A who are treated with
      prophylaxis or receive on-demand treatments may represent a winning strategy with
      which to resolve the outstanding issues related to health technology assessments
      in the care of patients with hemophilia.

PMID- 25976057
TI  - Histomonosis - an existing problem in chicken flocks in Poland.
AB  - Histomonosis (histomoniasis, blackhead), beside coccidiosis, belongs to the most
      important parasitic protozoan diseases in poultry. So far Histomonas meleagridis
      infections with varied mortality rates have been mainly diagnosed in young
      turkeys. Recently an increasing number of cases have been reported in chicken
      flocks in Europe resulting in economic losses. It is thought that this situation
      is predominantly caused by a complete withdrawal of the effective antihistomonals
      in the EU. Authors listed the selected outbreaks of histomonosis in 10 chicken
      flocks originated from different farms of 4 regions in Poland: 8 broiler breeder
      flocks (at mean age of 33 weeks) and 2 commercial layers flocks (at mean age of
      38 weeks). This study reported here naturally occurring case of H.meleagridis
      infection in commercial broiler breeder (BB) flock line ROSS 308 at the age of 16
      weeks. We showed acute form of infection with characteristic necrotic foci in the
      liver, and ulcerative typhilitis. Beside the liver and caeca, the multiple
      histomonads, lymphoid tissue depletion and heavy destruction in the bursa of
      Fabricius were observed. Additionally, the absence of systemic diffuse
      histomonads and lack of Heterakis gallinarum, caecal worm eggs in faecal samples
      were noted. PCR technique enabled to detect the presence of H.meleagridis genetic
      material in the investigated tissue samples. Authors indicate that histomonosis
      can be considered as re-emerging infectious diseases in chicken flocks of
      intensive production system.

PMID- 25976058
TI  - Dendrimers incorporating benzenesulfonamide moieties strongly inhibit carbonic
      anhydrase isoforms I-XIV.
AB  - As extension of our previous study herein we report a comprehensive investigation
      of poly(amidoamine) (PAMAM) dendrimers as modulators of the human carbonic
      anhydrase (hCA, EC 4.2.1.1) isoforms I-XIV. Interestingly inhibitory activity was
      observed for the non-functionalized dendrimers against the hCA I, VII, IX, XII
      and XIV isoforms, whereas activation properties were reported only for the
      cytosolic abundant hCA II. Highly efficient inhibitory action against many
      isoforms having medicinal chemistry applications, such as hCA II, V, VII, IX, XII
      and XIV, was observed for the PAMAM functionalized counterparts bearing 4, 8, 16
      and 32 benzenesulfonamide moieties. Possible applications of dendrimer-CA
      inhibitors as therapeutic/diagnostic agents are envisaged. 

PMID- 25976059
TI  - Effects of postweaning administration of conjugated linoleic acid on development
      of obesity in nescient basic helix-loop-helix 2 knockout mice.
AB  - Conjugated linoleic acid (CLA) has been reported to prevent body weight gain and
      fat accumulation in part by improving physical activity in mice. However, the
      effects of postweaning administration of CLA on the development of obesity later
      in life have not yet been demonstrated. The current study investigated the role
      of postweaning CLA treatment on skeletal muscle energy metabolism in genetically
      induced inactive adult-onset obese model, nescient basic helix-loop-helix 2
      knockout (N2KO) mice. Four-week-old male N2KO and wild type mice were fed either
      control or a CLA-containing diet (0.5%) for 4 weeks, and then CLA was withdrawn
      and control diet provided to all mice for the following 8 weeks. Postweaning CLA
      supplementation in wild type animals, but not N2KO mice, may activate AMP
      activated protein kinase (AMPK) and peroxisome proliferator-activated receptor
      delta (PPARdelta) as well as promote desensitization of phosphatase and tensin
      homologue (PTEN) and sensitization of protein kinase B (AKT) at threonine 308 in
      gastrocnemius skeletal muscle, improving voluntary activity and glucose
      homeostasis. We suggest that postweaning administration of CLA may in part
      stimulate the underlying molecular targets involved in muscle energy metabolism
      to reduce weight gain in normal animals, but not in the genetically induced
      inactive adult-onset animal model. 

PMID- 25976060
TI  - MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's
      Disease by Targeting to Bim.
AB  - Parkinson's disease (PD) is the most prevalent movement disorder characterized by
      selective loss of midbrain dopaminergic (DA) neurons. MicroRNA-124 (miR-124) is
      abundantly expressed in the DA neurons and its expression level decreases in the
      1-methyl-4-pheny-1, 2, 3, 6-tetrahydropyridine (MPTP) model of PD. However,
      whether the upregulation of miR-124 could attenuate neurodegeneration remains
      unknown. Here, we employed miR-124 agomir and miR-124 mimics to upregulate miR
      124 expression in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells,
      respectively. We found that loss of DA neurons and striatal dopamine in MPTP
      treated mice was significantly reduced by upregulating miR-124. In addition, we
      identified a target of miR-124, Bim that mediated the neuroprotection of miR-124.
      Indeed, treatment of miR-124 agomir in MPTP-treated mice inhibited Bim
      expression, thus suppressing Bax translocation to mitochondria. Moreover,
      impaired autophagy process in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y
      cells characterized as autophagosomes (AP) accumulation and lysosomal depletion
      were alleviated by the upregulation of miR-124. Taken together, these results
      indicate that upregulation of miR-124 could regulate apoptosis and impaired
      autophagy process in the MPTP model of PD, thus reducing the loss of DA neurons. 

PMID- 25976061
TI  - Use of Evidence-Based Practice and Barriers to Utilize Research in Rural Social
      Work Practice.
AB  - In this study the author explores the level of use of evidence-based practice and
      the extent of barriers to research utilization in rural practice settings. Ninety
      one social work field instructors from the rural areas of Southeast Ohio reported
      moderate use of evidence-based practice in their treatment process. The majority
      of field instructors also identified significant barriers to research utilization
      in practice. In addition, the use of evidence-based practice was associated with
      barriers to utilize research in the areas of field instructors' characteristics,
      organizational settings and limits, and communication. Implications include
      suggestions for enhancing evidence-based practice in rural settings.

PMID- 25976062
TI  - ISAC's Gating-ML 2.0 data exchange standard for gating description.
AB  - The lack of software interoperability with respect to gating has traditionally
      been a bottleneck preventing the use of multiple analytical tools and
      reproducibility of flow cytometry data analysis by independent parties. To
      address this issue, ISAC developed Gating-ML, a computer file format to encode
      and interchange gates. Gating-ML 1.5 was adopted and published as an ISAC
      Candidate Recommendation in 2008. Feedback during the probationary period from
      implementors, including major commercial software companies, instrument vendors,
      and the wider community, has led to a streamlined Gating-ML 2.0. Gating-ML has
      been significantly simplified and therefore easier to support by software tools.
      To aid developers, free, open source reference implementations, compliance tests,
      and detailed examples are provided to stimulate further commercial adoption. ISAC
      has approved Gating-ML as a standard ready for deployment in the public domain
      and encourages its support within the community as it is at a mature stage of
      development having undergone extensive review and testing, under both theoretical
      and practical conditions.

PMID- 25976063
TI  - Carbetocin versus intra-umbilical oxytocin in the management of retained
      placenta: a randomized clinical study.
AB  - AIM: This study aimed to compare the hemodynamic profile and efficacy of
      carbetocin versus intra-umbilical oxytocin in the management of retained placenta
      following vaginal delivery. MATERIAL AND METHODS: In this randomized clinical
      study, women with retained placenta for more than 30 min were assigned to receive
      either an i.v. bolus of 100-ug carbetocin (n = 38) or an intra-umbilical vein
      injection of 50 IU oxytocin in 30 mL saline (n = 40). The main parameters
      evaluated were the success rate for expulsion of the placenta and the effects of
      these drugs on maternal blood pressure. RESULTS: The success rate in the
      carbetocin group was 86.84% compared to 77.5% in the intra-umbilical oxytocin
      group. Notably, 57.7% of the participants had prior induction of labor or
      augmentation during labor. There were no significant differences between the two
      groups regarding the estimated blood loss, drop of hemoglobin within the first 48
      h, additional uterotonic injection or the need for manual removal of the
      placenta. Systolic blood pressure was significantly lower in the intra-umbilical
      oxytocin group at 30 and 60 min after injection (P = 0.008, 0.026, respectively).
      Nonetheless, diastolic blood pressure was significantly lower in the intra
      umbilical oxytocin group than in the carbetocin group at 30 min (P = 0.036).
      CONCLUSION: A single i.v. bolus of carbetocin and umbilical vein injection of 50
      IU oxytocin are similarly effective in reducing the need for manual removal of
      the placenta. Carbetocin seems to have an acceptable hemodynamic safety profile
      and can be used as an alternative choice to the conventional oxytocic agents in
      the management of retained placenta.

PMID- 25976064
TI  - Effectiveness of a hybrid corticosteroid treatment regimen on refractory
      childhood seizures and a review of other corticosteroid treatments.
AB  - BACKGROUND: Many different corticosteroid treatment schedules have been used in
      order to treat refractory epileptic seizures with encouraging effects on seizure
      reduction in many epileptic syndromes. OBJECTIVE: The objective is to report our
      experience with a hybrid treatment regimen for refractory seizures in children
      with epilepsies other than West and Landau-Kleffner syndrome. We hypothesized
      that a pulse of corticosteroids effectively reduces seizures while low-dosage
      maintenance treatment reduces side effects. The results are compared with results
      from a review of reported corticosteroid and ACTH treatments. METHODS: In this
      retrospective observational study, 26 children diagnosed with epilepsy with
      refractory seizures other than West syndrome and Landau-Kleffner syndrome were
      eligible for a treatment regimen consisting of three days intravenous
      methylprednisolone (20 mg per kilogram per day) followed by twelve weeks oral
      prednisolone (0.5 mg per kilogram on alternate days), concluded with a taper
      phase. Data on effectiveness and side effects were obtained. End-points were the
      percentages of patients who became seizure free or responded well. RESULTS:
      Twenty-one patients received the study treatment. Nine (43%) responded well and 6
      (29%) became seizure free. All but one patient had a relapse of seizures. Four
      patients had reversible adverse effects. Data extracted from the literature were
      consistent with a good response in 48% of 192 children treated with different
      corticosteroids and in 69% of 103 patients treated with ACTH. CONCLUSION: This
      new hybrid therapy of a pulse of intravenous methylprednisolone and alternate day
      oral prednisolone is effective with a favourable side effect profile. Results on
      efficacy and safety justify a randomized controlled trial.

PMID- 25976065
TI  - Diagnostic overshadowing in a population of children with neurological
      disabilities: A cross sectional descriptive study on acquired ADHD.
AB  - AIM: Diagnostic overshadowing refers to the underdiagnosis of comorbid conditions
      in children with known neurological diagnoses. To demonstrate diagnostic
      overshadowing we determined the prevalence of attention deficit-hyperactivity
      disorders (ADHD) in a cohort of children with a wide range of neurological
      disabilities. METHOD: The study cohort consisted of 685 children (mean age 10.3
      years, SD: 3.1; 425 boys and 260 girls) who visited a tertiary outpatient
      multidisciplinary clinic for neurological learning disabilities. Patients with
      ADHD were identified by retrospective chart review using DSM-IV criteria.
      RESULTS: The prevalence of ADHD in this cohort was 38.8% (266 children); of these
      children only 28.2% (75 children) were diagnosed with ADHD before referral.
      INTERPRETATION: ADHD is a common problem in children with neurological
      disabilities and may be underdiagnosed due to overshadowing of somatic, physical
      or syndromal features of the disability. In our heterogeneous population ADHD was
      overshadowed in 71.8% of the cases. This finding may have important implications
      for diagnosis and treatment of mental health needs in children with neurological
      disabilities.

PMID- 25976066
TI  - Hemispherotomy for isolated infantile spasms following perinatal ischemic stroke.
AB  - BACKGROUND: Infantile spasms (IS) are a severe epileptic encephalopathy. In
      patients with early focal ischemia and refractory IS, a preoperative evaluation
      is required even if IS are the only ictal manifestation. METHODS: We report three
      such patients who presented with IS between 5 and 7 months of age without any
      other focal seizure types. Imaging exhibited a perinatal middle cerebral artery
      (MCA) stroke. RESULTS: All patients had hemiparesis and experienced psychomotor
      regression after the onset of IS. Scalp video-electroencephalogram (EEG)
      monitoring for presurgical assessment showed interictal and ictal EEG
      characteristics between the pathological and the healthy hemisphere and surgery
      was proposed despite the lack of any focal seizures. The three patients underwent
      hemispherotomy at a mean age of 27 months and became seizure-free without
      medication (follow-up 49-144 months). The two patients who underwent early
      hemispherotomy acquired normal verbal intelligence, whereas the third, operated
      on at 38 months of age, remained with severe mental retardation. CONCLUSION:
      Early hemispherotomy in drug-resistant epilepsy related to a perinatal MCA may
      cure the seizures even if the patient has IS as sole type and prevent mental
      retardation in some children.

PMID- 25976067
TI  - Word and text processing in acquired prosopagnosia.
AB  - OBJECTIVE: A novel hypothesis of object recognition asserts that multiple regions
      are engaged in processing an object type, and that cerebral regions participate
      in processing multiple types of objects. In particular, for high-level expert
      processing, it proposes shared rather than dedicated resources for word and face
      perception, and predicts that prosopagnosic subjects would have minor deficits in
      visual word processing, and alexic subjects would have subtle impairments in face
      perception. In this study, we evaluated whether prosopagnosic subjects had
      deficits in processing either the word content or the style of visual text.
      METHODS: Eleven prosopagnosic subjects, 6 with unilateral right lesions and 5
      with bilateral lesions, participated. In the first study, we evaluated their word
      length effect in reading single words. In the second study, we assessed their
      time and accuracy for sorting text by word content independent of style, and for
      sorting text by handwriting or font style independent of word content. RESULTS:
      Only subjects with bilateral lesions showed mildly elevated word length effects.
      Subjects were not slowed in sorting text by word content, but were nearly
      uniformly impaired in accuracy for sorting text by style. INTERPRETATION: Our
      results show that prosopagnosic subjects are impaired not only in face
      recognition but also in perceiving stylistic aspects of text. This supports a
      modified version of the many-to-many hypothesis that incorporates hemispheric
      specialization for processing different aspects of visual text.

PMID- 25976068
TI  - An approach for identification of unknown viruses using sequencing-by
      hybridization.
AB  - Accurate identification of biological threat agents, especially RNA viruses, in
      clinical or environmental samples can be challenging because the concentration of
      viral genomic material in a given sample is usually low, viral genomic RNA is
      liable to degradation, and RNA viruses are extremely diverse. A two-tiered
      approach was used for initial identification, then full genomic characterization
      of 199 RNA viruses belonging to virus families Arenaviridae, Bunyaviridae,
      Filoviridae, Flaviviridae, and Togaviridae. A Sequencing-by-hybridization (SBH)
      microarray was used to tentatively identify a viral pathogen then, the identity
      is confirmed by guided next-generation sequencing (NGS). After optimization and
      evaluation of the SBH and NGS methodologies with various virus species and
      strains, the approach was used to test the ability to identify viruses in blinded
      samples. The SBH correctly identified two Ebola viruses in the blinded samples
      within 24 hr, and by using guided amplicon sequencing with 454 GS FLX, the
      identities of the viruses in both samples were confirmed. SBH provides at
      relatively low-cost screening of biological samples against a panel of viral
      pathogens that can be custom-designed on a microarray. Once the identity of virus
      is deduced from the highest hybridization signal on the SBH microarray, guided
      (amplicon) NGS sequencing can be used not only to confirm the identity of the
      virus but also to provide further information about the strain or isolate,
      including a potential genetic manipulation. This approach can be useful in
      situations where natural or deliberate biological threat incidents might occur
      and a rapid response is required.

PMID- 25976069
TI  - Simple and rapid screening procedure for 143 new psychoactive substances by
      liquid chromatography-tandem mass spectrometry.
AB  - In recent years, many new psychoactive substances (NPS) from several drug classes
      have appeared on the drug market. These substances, also known as 'legal highs',
      belong to different chemical classes. Despite the increasing number of NPS, there
      are few comprehensive screening methods for their detection in biological
      specimens. In this context, the purpose of this study was to develop a fast and
      simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening
      procedure for NPS in blood. The elaborated method allows the simultaneous
      screening of 143 compounds from different groups (number of compounds):
      cathinones (36), phenethylamines (26), tryptamines (18), piperazines (9),
      piperidines (2), synthetic cannabinoids (34), arylalkylamines (7),
      arylcyclohexylamines (3), aminoindanes (2), and other drugs (6). Blood samples
      (0.2 mL) were precipitated with acetonitrile (0.6 mL). The separation was
      achieved with gradient mobile phase of 0.1% formic acid in acetonitrile and 0.1%
      formic acid in water in 14 min. Detection of all compounds was based on multiple
      reaction monitoring (MRM) transitions. The total number of transitions monitored
      in dynamic mode was 432. The whole procedure was rapid and simple. The limits of
      detection (LODs) estimated for 104 compounds were in the range 0.01-3.09 ng/mL.
      The extraction recoveries determined for 32 compounds were from 1.8 to 133%. The
      procedure was successfully applied to the analysis of forensic blood samples in
      routine casework. The developed method should have wide applicability for rapid
      screening of new drugs of abuse in forensic or clinical samples. The procedure
      can be easily expanded for more substances. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 25976070
TI  - Coregulation of respiratory sinus arrhythmia between parents and preschoolers:
      differences by children's externalizing problems.
AB  - The coordination of physiological processes between parents and infants is
      thought to support behaviors critical for infant adaptation, but we know little
      about parent-child physiological coregulation during the preschool years. The
      present study examined whether time-varying changes in parent and child
      respiratory sinus arrhythmia (RSA) exhibited coregulation (across-person
      dynamics) accounting for individual differences in parent and child RSA, and
      whether there were differences in these parasympathetic processes by children's
      externalizing problems. Mother-child dyads (N = 47; Child age M = 31/2 years)
      engaged in three laboratory tasks (free play, clean up, puzzle task) for 18 min,
      during which RSA data were collected. Multilevel coupled autoregressive models
      revealed that mothers and preschoolers showed positive coregulation of RSA such
      that changes in mother RSA predicted changes in the same direction in child RSA
      and vice versa, controlling for the stability of within-person RSA over time and
      individual differences in overall mean RSA. However, when children's
      externalizing behaviors were higher, coregulation was negative such that changes
      in real-time mother and child RSA showed divergence rather than positive
      concordance. Results suggest that mothers and preschoolers do coregulate RSA
      during real-time interactions, but that children's higher externalizing behavior
      problems are related to disruptions in these processes.

PMID- 25976072
TI  - Intra-arterial Administration of Placenta-Derived Decidual Stromal Cells to the
      Superior Mesenteric Artery in the Rabbit: Distribution of Cells, Feasibility, and
      Safety.
AB  - Selective administration of mesenchymal stromal cells to the mesenteric arteries
      is a potential technique to overcome pulmonary trapping and increase the density
      of transplanted cells in extensive mural inflammation of the intestine, such as
      in inflammatory bowel disease and graft-versus-host disease. We injected 5 *
      10(6) (111)In-oxine-labeled human decidual stromal cells (DSCs) to the rabbit
      superior mesenteric artery (SMA) using clinical routine catheters guided by an
      angiographical system under sterile conditions. We used longitudinal single
      photon emission tomography at 6 h and at 1, 2, and 5 days to assess trafficking
      and distribution of DSCs. We used digital subtraction angiography, computed
      tomography, and hematoxylin and eosin stainings to determine biodistribution of
      cells and to assess safety end points. We found that selective injection of human
      DSCs to the rabbit SMA does not result in acute embolic complications.
      Furthermore, we found that IV administration resulted in extensive retention of
      the radiolabeled DSCs in the lungs, corroborating previous studies on pulmonary
      trapping. In sharp contrast, selective injections to the SMA resulted in uptake
      distributed in the intestine supplied by the SMA and in the liver, indicating
      that this approach could significantly increase the fraction of injected DSCs
      reaching the target tissue. 

PMID- 25976071
TI  - Helical growth of aluminum nitride: new insights into its growth habit from
      nanostructures to single crystals.
AB  - By understanding the growth mechanism of nanomaterials, the morphological
      features of nanostructures can be rationally controlled, thereby achieving the
      desired physical properties for specific applications. Herein, the growth habits
      of aluminum nitride (AlN) nanostructures and single crystals synthesized by an
      ultrahigh-temperature, catalyst-free, physical vapor transport process were
      investigated by transmission electron microscopy. The detailed structural
      characterizations strongly suggested that the growth of AlN nanostructures
      including AlN nanowires and nanohelixes follow a sequential and periodic rotation
      in the growth direction, which is independent of the size and shape of the
      material. Based on these experimental observations, an helical growth mechanism
      that may originate from the coeffect of the polar-surface and dislocation-driven
      growth is proposed, which offers a new insight into the related growth kinetics
      of low-dimensional AlN structures and will enable the rational design and
      synthesis of novel AlN nanostructures. Further, with the increase of temperature,
      the growth process of AlN grains followed the helical growth model. 

PMID- 25976073
TI  - Morphometric analysis of the diameter and g-ratio of the myelinated nerve fibers
      of the human sciatic nerve during the aging process.
AB  - Myelinated nerve fibers suffer from different degrees of atrophy with age. The
      success of subsequent regeneration varies. The aim of this research was to
      analyze myelinated fibers of the human sciatic nerve during the aging process.
      Morphometric analysis was performed on 17 cases with an age range from 9 to 93
      years. The outer and inner diameter of 100 randomly selected nerve fibers was
      measured in each of the cases evaluated, and the g-ratio (axonal diameter/outer
      diameter of the whole nerve fiber) of each was calculated. Scatter plots of the
      diameters and g-ratios of the analyzed fibers were then analyzed. Nerve fibers of
      each case were classified into three groups according to the g-ratio values:
      group I (g-ratio lower than 0.6), group II (g-ratio from 0.6 to 0.7) and group
      III (g-ratio higher than 0.7). Afterwards, nerve fibers of group II were further
      classified into small and large subgroups. The percentages of each group of nerve
      fibers were computed for each case and these values were used for correlational
      and bivariate linear regression analysis. The percentage of myelinated nerve
      fibers with large diameter and optimal g-ratio of the sciatic nerve declines
      significantly with age. This is accompanied by a simultaneous significant
      increase in the percentage of small myelinated fibers with g-ratio values close
      to 1 that occupy the upper left quadrant of the scatter plot. It can be concluded
      that aging of the sciatic nerve is associated with significant atrophy of large
      myelinated fibers. Additionally, a significant increase in regenerated nerve
      fibers with thinner myelin sheath is observed with age, which, together with the
      large myelinated fiber atrophy, might be the cause of the age-related decline in
      conduction velocity. A better understanding of the changes in aging peripheral
      nerves might improve interpretation of their pathological changes, as well as
      comprehension of their regeneration in individuals of different age. 

PMID- 25976075
TI  - Prevention in high-risk patients: a long-term committment.

PMID- 25976074
TI  - IRE1alpha-XBP1 Pathway Is Activated Upon Induction of Single-Prolonged Stress in
      Rat Neurons of the Medial Prefrontal Cortex.
AB  - Endoplasmic reticulum stress (ERS) is associated with many nervous system
      diseases. IRElalpha is considered as ERS sensor that, upon activation, initiates
      the nonconventional splicing of the precursor unspliced form of X-box binding
      protein 1 (XBP1u) messenger RNA (mRNA) to yield an active transcription factor
      XBP1s. The goal of this study is to detect whether there is activation of
      IRE1alpha-XBP1 pathway in the medial prefrontal cortex (mPFC) of posttraumatic
      stress disorder (PTSD) model rats. This study adopted single-prolonged stress
      (SPS) model. Behavioral functions including anxiety-like behavior, exploration
      behavior, and spatial memory were assessed by open field test and Morris water
      maze test. We detected the IRE1alpha and XBP1 by using methods of double-labeling
      immunofluorescence, Western blot, and quantitative real-time reverse
      transcription-PCR (qRT-PCR). We also observed neuronal apoptosis by transferase
      mediated dUTP Nick-end-labeling (TUNEL) staining and the expression of caspase-12
      by qRT-PCR. Our results showed that the expression of IRE1alpha, XBP1u, and total
      XBP1 significantly increased at 1 day after SPS and then decreased gradually. At
      the same time, XBP1s appeared and peaked at 4 days after SPS, which indicated
      that IRE1alpha-XBP1 pathway was activated upon induction of SPS stimulation. We
      also noted that the mRNA of caspase-12 was upregulated after SPS. Our study
      preliminarily showed that ERS mediated by IRE1alpha-XBP1 pathway was closely
      related to PTSD and it might be a pathogenesis of PTSD. 

PMID- 25976076
TI  - Calls for a higher level of professionalism in biomedical research.
AB  - Many researchers are so keen to investigate new ideas that they fail to carry out
      essential pre-research and post-research studies, according to a growing band of
      health services academics.

PMID- 25976077
TI  - Introducing keytagging, a novel technique for the protection of medical image
      based tests.
AB  - This paper introduces keytagging, a novel technique to protect medical image
      based tests by implementing image authentication, integrity control and location
      of tampered areas, private captioning with role-based access control,
      traceability and copyright protection. It relies on the association of tags
      (binary data strings) to stable, semistable or volatile features of the image,
      whose access keys (called keytags) depend on both the image and the tag content.
      Unlike watermarking, this technique can associate information to the most stable
      features of the image without distortion. Thus, this method preserves the
      clinical content of the image without the need for assessment, prevents
      eavesdropping and collusion attacks, and obtains a substantial capacity
      robustness tradeoff with simple operations. The evaluation of this technique,
      involving images of different sizes from various acquisition modalities and image
      modifications that are typical in the medical context, demonstrates that all the
      aforementioned security measures can be implemented simultaneously and that the
      algorithm presents good scalability. In addition to this, keytags can be
      protected with standard Cryptographic Message Syntax and the keytagging process
      can be easily combined with JPEG2000 compression since both share the same
      wavelet transform. This reduces the delays for associating keytags and retrieving
      the corresponding tags to implement the aforementioned measures to only ?30 and
      ?90ms respectively. As a result, keytags can be seamlessly integrated within
      DICOM, reducing delays and bandwidth when the image test is updated and shared in
      secure architectures where different users cooperate, e.g. physicians who
      interpret the test, clinicians caring for the patient and researchers. 

PMID- 25976078
TI  - Present standards and future perspectives in the treatment of metastatic non
      small cell lung cancer.
AB  - The development of novel effective immunotherapeutic agents and early clinical
      data hinting at significant activity in non-small cell lung cancer (NSCLC) has
      introduced yet another player in the field of management of advanced disease. At
      present, first-line cytotoxic chemotherapy is generally withheld pending results
      of molecular testing for any actionable genetic alteration that could lead to
      targeted treatment, and in their absence chemotherapy is prescribed as a default
      therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors
      with standard platinum-based doublet chemotherapy are underway. Second-line
      chemotherapy is likewise being challenged in phase III trials, one of which
      having recently reported positive results in advanced squamous cell carcinoma. In
      tumors harboring actionable transforming genetic alterations such as EGFR
      mutations and ALK rearrangements, second- and third-generation inhibitors allow
      for multiple lines of targeted treatment beyond initial resistance, postponing
      the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as
      a longstanding but still present standard of care capable of prolonging survival,
      improving quality of life, and relieving symptoms sees its role increasingly
      restricted to clinical, immunological, and molecular subsets of patients where
      its activity and efficacy have never been tested prospectively. 

PMID- 25976079
TI  - Very small embryonic-like stem cells are involved in pancreatic regeneration and
      their dysfunction with age may lead to diabetes and cancer.
AB  - Mouse pancreas has a remarkable ability to regenerate after partial
      pancreatectomy, and several investigators have studied the underlying mechanisms
      involved in this regeneration process; however, the field remains contentious.
      Elegant lineage-tracing studies undertaken over a decade have generated strong
      evidence against neogenesis from stem cells and in favor of reduplication of pre
      existing islets. Ductal epithelium has also been implicated during regeneration.
      We recently provided direct evidence for the possible involvement of very small
      embryonic-like stem cells (VSELs) during regeneration after partial
      pancreatectomy in mice. VSELs were first reported in pancreas in 2008 and are
      mobilized in large numbers after treating mice with streptozotocin and in
      patients with pancreatic cancer. VSELs can be detected in mouse pancreas as small
      sized LIN(-)/CD45(-)/SCA-1(+) cells (3 to 5 MUm), present in small numbers
      (0.6%), which express nuclear Oct-4 (octamer-binding transcription factor 4) and
      other pluripotent markers along with their immediate descendant 'progenitors',
      which are slightly bigger and co-express Oct-4 and PDX-1. VSELs and the
      progenitors get mobilized in large numbers after partial pancreatectomy and
      regenerate both pancreatic islets and acinar cells. In this review, we deliberate
      upon possible reasons why VSELs have eluded scientists so far. Because of their
      small size, VSELs are probably unknowingly and inadvertently discarded during
      processing. Similar to menopause and related loss of ovarian function, type 2
      diabetes mellitus occurs because of a decline in beta-cell function possibly
      resulting from an age-related compromised niche which does not allow VSELs to
      maintain normal homeostasis. As suggested earlier for ovarian cancers, the
      presence of Oct-4 and other pluripotent markers in pancreatic cancers is
      suggestive of VSELs as the possible cancer-initiating stem cells. Several issues
      raised in the review require urgent confirmation and thus provide scope for
      further research before arriving at a consensus on the fundamental role played by
      VSELs in normal pancreas biology and during regeneration, aging, and cancer. In
      the future, such understanding may allow manipulation of endogenous VSELs to our
      advantage in patients with diabetes and also to treat cancer. 

PMID- 25976080
TI  - Depression during Pregnancy.
AB  - A proportion of women enter pregnancy with active psychiatric symptoms or
      disorders, with or without concomitant psychotropic medication. Studies report
      that exposure to untreated depression and stress during pregnancy may have
      negative consequences for birth outcome and child development. Studies also
      report that antenatal exposure to antidepressant medications may have adverse
      consequences for birth outcome and child development. Antidepressant medication
      use during pregnancy leads to a small increased risk of miscarriage, a possible
      small increased risk of congenital cardiac malformations, a small increased risk
      of preterm birth, a small increased risk of persistent pulmonary hypertension of
      the newborn (PPHN), and transient neonatal symptoms in up to one-third of
      neonates. In addition, there is a possible increased risk of delayed motor
      development in children. Several recent systematic reviews and meta-analyses of
      the existent literature emphasize that there are minimal definitive conclusions
      to guide treatment recommendations. This review describes best practices for the
      management of depression in pregnancy, and it provides suggestions for future
      research. 

PMID- 25976081
TI  - Gemcitabine treatment enhances HER2 expression in low HER2-expressing breast
      cancer cells and enhances the antitumor effects of trastuzumab emtansine.
AB  - Trastuzumab emtansine (T-DM1), trastuzumab-conjugated with a cytotoxic agent, has
      shown promising antitumor effects in breast cancer. Since a good therapeutic
      response using T-DM1 treatment requires high human epidermal growth factor
      receptor 2 (HER2) expression, breast cancers with low or no HER2 expression have
      not been used for T-DM1 treatment. The aim of the present study was to show that
      treatment of low HER2-expressing breast cancer cells with gemcitabine (GEM)
      enhanced HER2 expression using RT-qPCR, immunoblot and flow cytometric analysis.
      The results showed that GEM treatment significantly enhanced HER2 expression in
      MDA-MB-231, MCF7 and BT-20 breast cancer cells, while paclitaxel (PTX) treatment
      induced lower or no enhancement in HER2 expression. The expression of HER2 mRNA
      was also enhanced in GEM-treated MCF7 cells. Treatment with an inhibitor for
      nuclear factor-(NF)-kappaB suppressed GEM-induced HER2 upregulation, indicating
      that NF-kappaB activation by GEM may be associated with HER2 upregulation. T-DM1
      binding to HER2 on MCF-7 cells was enhanced by GEM pretreatment and the combined
      treatment of GEM and T-DM1 synergistically inhibited the proliferation of MCF7
      cells. Thus, the combined treatment with GEM and T-DM1 may be a promising
      therapeutic modality for low HER2-expressing breast cancers, which was
      facilitated by the unique HER2-upregulating effect of GEM.

PMID- 25976082
TI  - Corrigendum: MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance
      and virulence in guinea pigs.

PMID- 25976084
TI  - [Spare-parts concept in pediatric hand: About one bilateral syndactyly].
AB  - INTRODUCTION: The spare-parts concept is well described in traumatology of the
      hand. Tissues of a scarified ray are used to reconstruct another damaged finger.
      We will detail an application in pediatric hand through a clinical case.
      MATERIALS AND METHOD: We describe a patient presenting a bilateral complete and
      non-complex syndactyly of the third web space associated with a bilateral
      hexadactyly classified as type B according to the Temtamy and Mc Kusick's
      classification. The treatment of the syndactyly was performed with a dorsal flap
      for the web space and with longitudinal zigzag incisions in mirror. Skin loss of
      the lateral sides of the fingers was covered by the full-thickness graft taken on
      the supernumerary finger which was treated in the same surgical time. DISCUSSION:
      This application of the spare-parts concept allows only one surgical site with
      absence of scar on the donor site and a skin graft close to the skin loss on the
      finger. CONCLUSION: The spare-parts concept can be applied in some cases of
      pediatric hand and must be a tool for the surgeon.

PMID- 25976086
TI  - "You have to go through it and have your children": reproductive experiences
      among women with vulvodynia.
AB  - BACKGROUND: Vulvodynia is a potentially debilitating chronic pain condition
      affecting the vulva (external genitalia) in women, with typical age of onset
      during the early-to mid-reproductive years. Yet, virtually nothing is known about
      the thoughts, feelings and experience of vulvodynia patients regarding
      conception, pregnancy and delivery; including the effect that a hallmark symptom,
      dyspareunia (painful sex), can have on a couple's physical and emotional ability
      to conceive. We sought to describe these experiences and beliefs among women with
      vulvodynia who were pregnant or who recently had delivered a child. METHODS: The
      study used in-depth, qualitative exploratory interview methods to gain a deeper
      understanding of these experiences for 18 women with vulvar pain who were
      recruited from an existing, nationally-sampled prospective pregnancy cohort
      study. RESULTS: Four major themes were reported by our participants. Women
      described their reaction to pain as volatile at first, and, over time, more self
      controlled, regardless of medical treatment; once the volatility became more
      stable and overall severity lessened, many women began planning for pregnancy.
      Techniques described by women to cope with pain around pregnancy included pain
      minimization, planning pregnancy-safe treatment and timing intercourse around
      ovulation. Regardless of the degree to which interaction with health care
      providers before pregnancy were positive, most participants developed mistrustful
      attitudes toward future dealings with health care systems and providers. Nearly
      all women described anxiety regarding how pregnancy may change pain symptoms, yet
      described being hopeful. CONCLUSIONS: Women described strategies regarding
      reproduction such as finding a personally acceptable level of pain before
      planning pregnancy, and a resilience that allowed them to achieve their
      reproductive goals despite pain and perceived lack of assistance from healthcare
      providers. Therefore, future research should assess the benefits of increased
      psychosocial support from partners and professionals who may assist in improving
      resilience.

PMID- 25976087
TI  - N-2-Aryl-1,2,3-Triazoles: A Novel Class of Blue Emitting Fluorophores-Synthesis,
      Photophysical Properties Study and DFT Computations.
AB  - Novel fluorescent 2-[4-(4,5-diphenyl-1H-imidazol-2-yl) phenyl]-2H-naphtho [1,2-d]
      [1,2,3] triazolyl derivatives were synthesized from 4-(4,5-diphenyl-1H-imidazol-2
      yl) aniline and substituted naphthalen-2-amine. The photophysical properties of
      the three new fluorophores were evaluated in acetonitrile, methanol,
      dimethylsulfoxide and N,N-dimethylformamide solvents and were compared with the
      reported analogs. The compounds show the absorption in the ultraviolet region and
      the emission in the blue region. The thermal stabilities of these compounds was
      evaluated by thermogravimetric analysis. The solvatochromism data are used for
      ground and excited state dipole moment determination of the synthesized triazoles
      using Bakhshiev and Bilot-Kawski correlations. The experimental absorption and
      emission were compared with the theoretical data obtained by DFT and TD-DFT
      computations and they are well in agreement with each other. 

PMID- 25976088
TI  - Cues for Diotic and Dichotic Detection of a 500-Hz Tone in Noise Vary with
      Hearing Loss.
AB  - Hearing in noise is a challenge for all listeners, especially for those with
      hearing loss. This study compares cues used for detection of a low-frequency tone
      in noise by older listeners with and without hearing loss to those of younger
      listeners with normal hearing. Performance varies significantly across different
      reproducible, or "frozen," masker waveforms. Analysis of these waveforms allows
      identification of the cues that are used for detection. This study included
      diotic (N0S0) and dichotic (N0Spi) detection of a 500-Hz tone, with either
      narrowband or wideband masker waveforms. Both diotic and dichotic detection
      patterns (hit and false alarm rates) across the ensembles of noise maskers were
      predicted by envelope-slope cues, and diotic results were also predicted by
      energy cues. The relative importance of energy and envelope cues for diotic
      detection was explored with a roving-level paradigm that made energy cues
      unreliable. Most older listeners with normal hearing or mild hearing loss
      depended on envelope-related temporal cues, even for this low-frequency target.
      As hearing threshold at 500 Hz increased, the cues for diotic detection
      transitioned from envelope to energy cues. Diotic detection patterns for young
      listeners with normal hearing are best predicted by a model that combines
      temporal- and energy-related cues; in contrast, combining cues did not improve
      predictions for older listeners with or without hearing loss. Dichotic detection
      results for all groups of listeners were best predicted by interaural envelope
      cues, which significantly outperformed the classic cues based on interaural time
      and level differences or their optimal combination. 

PMID- 25976089
TI  - Mining care trajectories using health administrative information systems: the use
      of state sequence analysis to assess disparities in prenatal care consumption.
AB  - BACKGROUND: Pregnant women are a vulnerable population. Although regular follow
      ups are recommended during pregnancy, not all pregnant women seek care. This
      pilot study wanted to assess whether the integration of data from administrative
      health information systems and socio-economic features allows identifying
      disparities in prenatal care trajectories. METHODS: Prenatal care trajectories
      were extracted from the permanent sample of the French health insurance
      information system linked to the hospital discharge information system. The
      records of 2518 women who gave birth without complications in France in 2009 were
      analyzed. State sequence data analysis was performed to identify homogeneous
      groups of prenatal care trajectories. Socio-economic data were used to
      characterize their living environment. RESULTS: We identified three groups of
      homogeneous prenatal care trajectories: (i) women with relatively high prenatal
      care consumption (~11%), (ii) women with no prenatal care (~21%), and (iii) women
      with an intermediate level of prenatal care (~66%). Analysis of the socio
      economic data demonstrated the association between disparities in prenatal care
      trajectories and the women's living environment. Women with relatively high care
      consumption generally lived in socio-economically privileged areas (better
      education levels, employment status and housing conditions) compared with women
      with few or no prenatal care. CONCLUSIONS: Although ecological, our approach
      demonstrates that data from health administrative information systems could be
      used to describe prenatal care. However, more individual variables and an
      improvement of the data quality are needed to efficiently monitor the content and
      timing of prenatal care. Moreover, state sequence analysis, which was used in
      this context for the first time, proves to be an interesting approach to explore
      care trajectories. Finally, the integration of heterogeneous sources of data,
      including contextual information, might help identifying areas that require
      health promotion actions toward vulnerable populations, such as pregnant women.

PMID- 25976090
TI  - An Initial Study Using Healing Touch for Women Undergoing a Breast Biopsy.
AB  - AIM: To determine if a noninvasive complementary therapy, Healing Touch, would
      benefit women undergoing diagnostic procedures for the determination of breast
      cancer. Women often experience high levels of fear and anxiety during this
      diagnostic period. STUDY DESIGN: A randomized controlled pilot study. METHOD: An
      out-patient clinic specializing in breast care management was used. Seventy-three
      women age 18 to 85 years old participated, with 31 in the control group of
      standard care and 42 in the intervention group receiving Healing Touch, a
      noninvasive energy therapy. A specific technique, magnetic clearing, was provided
      by a practitioner for 15 minutes prior to the biopsy procedure. Both the State
      Trait Anxiety Inventory and the Coping Resources Inventory were used
      preprocedurally and the following day to assess changes. RESULTS: A mixed
      analysis of variance indicated that State Anxiety for the Healing Touch group
      showed a statistically significant reduction of anxiety that was sustained into
      the following day, F(2, 142) = 10.94, p < .001. For Trait Anxiety, there was a
      significant change pre-and postintervention to the day after, F(2, 142) = 5.15, p
      < .007. The Coping Resources Inventory had significant changes in two
      subcategories, Emotional, F(2, 142) = 6.10, p = .003, and the
      Spiritual/Philosophical, F(2, 142) = 6.10, p < .001, in the Healing Touch group.
      CONCLUSION: Healing Touch may have benefit in reducing anxiety from diagnostic
      breast procedures.

PMID- 25976091
TI  - A "fact of the matter" may not exist in scientific narratives such as serotonin
      and depression.

PMID- 25976083
TI  - Insights into bombesin receptors and ligands: Highlighting recent advances.
AB  - This following article is written for Prof. Abba Kastin's Festschrift, to add to
      the tribute to his important role in the advancement of the role of peptides in
      physiological, as well as pathophysiological processes. There have been many
      advances during the 35 years of his prominent role in the Peptide field, not only
      as editor of the journal Peptides, but also as a scientific investigator and
      editor of two volumes of the Handbook of Biological Active Peptides [146,147].
      Similar to the advances with many different peptides, during this 35 year period,
      there have been much progress made in the understanding of the pharmacology, cell
      biology and the role of (bombesin) Bn receptors and their ligands in various
      disease states, since the original isolation of bombesin from skin of the
      European frog Bombina bombina in 1970 [76]. This paper will briefly review some
      of these advances over the time period of Prof. Kastin 35 years in the peptide
      field concentrating on the advances since 2007 when many of the results from
      earlier studies were summarized [128,129]. It is appropriate to do this because
      there have been 280 articles published in Peptides during this time on bombesin
      related peptides and it accounts for almost 5% of all publications. Furthermore,
      22 Bn publications we have been involved in have been published in either
      Peptides [14,39,55,58,81,92,93,119,152,216,225,226,231,280,302,309,355,361,362]
      or in Prof. Kastin's Handbook of Biological Active Peptides [137,138,331]. 

PMID- 25976092
TI  - Psora-4, a Kv1.3 Blocker, Enhances Differentiation and Maturation in Neural
      Progenitor Cells.
AB  - AIM: The self-repair ability of neural progenitor cells (NPCs) has been found to
      be activated and protected in several therapies helpful in multiple sclerosis
      (MS), an inflammatory demyelinating disease of the CNS. As a potential
      therapeutic target in MS, the role of the ion channel Kv1.3 in NPC self-repair
      has received limited attention. The aim of this study was to explore the effects
      of a selective Kv1.3 blocker on NPC neuronal differentiation and maturation.
      METHODS: A small-molecule selective blocker for Kv1.3, Psora-4, was added to the
      differentiation medium of cultured mouse NPCs to assess its effect on NPC
      differentiation efficiency. Both a polypeptide Kv1.3 blocker and Kv1.3-specific
      RNA interference were used in parallel experiments. Further, the maturity of
      newborn neurons in the presence of Psora-4 was measured both by morphological
      analysis and by whole-cell patch clamping. RESULTS: Psora-4 induced a significant
      increase in the percentage of neurons. Knockdown of Kv1.3 in NPCs also promoted
      neuronal differentiation. Both morphological and electrophysiological analyses
      suggested that NPC-derived neurons in the presence of Psora-4 were more mature.
      CONCLUSION: Our studies reveal a crucial role for the ion channel Kv1.3 in the
      regulation of NPC differentiation and maturation, making Psora-4 a promising
      candidate molecule for MS treatment.

PMID- 25976094
TI  - Differential involvement of IL-6 in the early and late phase of 1
      methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.
AB  - Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim
      of this work was to characterize the profile of release of endogenous MNA during
      the initiation and progression of murine hepatitis induced by Concanavalin A
      (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as
      well as the energy state of hepatocytes in MNA release in early and late phases
      of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and
      IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well
      as the energy state of hepatocytes, were analysed in relation to MNA release. The
      decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-?), acute
      phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase,
      ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to
      IL-6(+/+) mice. The release of MNA in response to Con A was also significantly
      blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of
      ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and
      aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma
      concentration was elevated to similar degree in the late stage after Concanavalin
      A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA
      induced hepatitis, early, but not late MNA release was IL-6-dependent. Our
      results suggest that in the initiation and early hepatitis, MNA release is linked
      to the energy deficit/impaired redox status in hepatocytes, while in a later
      phase, MNA release is rather linked to the systemic inflammation. 

PMID- 25976096
TI  - The unresolved role of dietary fibers on mineral absorption.
AB  - Dietary fiber is a complex nutritional concept whose definition and method of
      analysis has evolved over time. However, literature on the role of dietary fiber
      on mineral bioavailability has not followed pace. Although in vitro studies
      revealed mineral binding properties, both animal and human studies failed to show
      negative effects on mineral absorption, and even in some cases reported
      absorption enhancing properties. The existing literature suggests that dietary
      fibers have negative effects on mineral absorption in the gastrointestinal tract
      largely due to mineral binding or physical entrapment. However, colonic
      fermentation of dietary fibers may offset this negative effect by liberating
      bound minerals and promoting colonic absorption. However, existing studies are
      limited since they did not control for more potent mineral absorption inhibitors
      such as phytates and polyphenols. Animal studies have mostly been on rats and
      hence difficult to extrapolate to humans. Human studies have been mostly on
      healthy young men, who likely to have an adequate store of iron. The use of
      different types and amounts of fibers (isolated/added) with varying physiological
      and physicochemical properties makes it difficult to compare results. Future
      studies can make use of the opportunities offered by enzyme technologies to
      decipher the role of dietary fibers in mineral bioavailability.

PMID- 25976093
TI  - Focal myocardial fibrosis assessed by late gadolinium enhancement cardiovascular
      magnetic resonance in children and adolescents with dilated cardiomyopathy.
AB  - BACKGROUND: Different patterns of late gadolinium enhancement (LGE) including mid
      wall fibrosis using cardiovascular magnetic resonance (CMR) have been reported in
      adult patients presenting with non-ischemic dilated cardiomyopathy (DCM). In
      these studies, LGE was associated with pronounced LV remodelling and predicted
      adverse cardiac outcomes. Accordingly, the purpose of our study was to determine
      the presence and patterns of LGE in children and adolescents with DCM. METHODS:
      Patients <18 years of age presenting with severe congestive heart failure who
      were admitted for evaluation of heart transplantation at our centre underwent CMR
      examination which consisted of ventricular functional analysis and assessment of
      LGE for detection of myocardial fibrosis. Ischemic DCM was excluded by coronary
      angiography, and right ventricular endomyocardial biopsies ruled out acute
      myocarditis. RESULTS: Thirty-one patients (mean age 2.1 +/- 4.2 years) with
      severe LV dilatation (mean indexed LVEDV 136 +/- 48 ml/m(2)) and LV dysfunction
      (mean LV-EF 23 +/- 8%) were examined. LGE was detected in 5 of the 31 patients
      (16%) appearing in various patterns characterized as mid-wall (n = 1), focal
      patchy (n = 1), RV insertion site (n = 1) and transmural (n = 2). Based on
      histopathological analysis, 4 of the 5 LGE positive patients had lymphocytic
      myocarditis, whereas one patient was diagnosed with idiopathic DCM. CONCLUSIONS:
      In children and adolescents with DCM, focal histologically proven myocardial
      fibrosis is rarely detected by LGE CMR despite marked LV dilatation and severely
      depressed LV function. LGE occurred in various patterns and mostly in patients
      with inflammatory cardiomyopathy. It remains unclear whether myocardial fibrosis
      in childhood DCM reflects different endogenous repair mechanisms that enable
      favourable reverse remodelling. Larger trials are needed to assess the prognostic
      implications of LGE in childhood DCM.

PMID- 25976097
TI  - A natural experiment of the consequences of concentrating former prisoners in the
      same neighborhoods.
AB  - More than 600,000 prisoners are released from incarceration each year in the
      United States, and most end up residing in metropolitan areas, clustered within a
      select few neighborhoods. Likely consequences of this concentration of returning
      prisoners include higher rates of subsequent crime and recidivism. In fact, one
      half of released prisoners return to prison within only 3 y of release. The
      routine exposure to criminogenic influences and criminal opportunities portends a
      bleak future for individuals who reside in neighborhoods with numerous other ex
      prisoners. Through a natural experiment focused on post-Hurricane Katrina
      Louisiana, I examine a counterfactual scenario: If instead of concentrating ex
      prisoners in geographic space, what would happen to recidivism rates if ex
      prisoners were dispersed across space? Findings reveal that a decrease in the
      concentration of parolees in a neighborhood leads to a significant decrease in
      the reincarceration rate of former prisoners. 

PMID- 25976098
TI  - Correction for Sauter et al., Cross-cultural recognition of basic emotions
      through nonverbal emotional vocalizations.

PMID- 25976099
TI  - Correction for Alsio et al., Ikaros promotes early-born neuronal fates in the
      cerebral cortex.

PMID- 25976100
TI  - Equilibrium phase diagram of a randomly pinned glass-former.
AB  - We use computer simulations to study the thermodynamic properties of a glass
      former in which a fraction c of the particles has been permanently frozen. By
      thermodynamic integration, we determine the Kauzmann, or ideal glass transition,
      temperature [Formula: see text] at which the configurational entropy vanishes.
      This is done without resorting to any kind of extrapolation, i.e., [Formula: see
      text] is indeed an equilibrium property of the system. We also measure the
      distribution function of the overlap, i.e., the order parameter that signals the
      glass state. We find that the transition line obtained from the overlap coincides
      with that obtained from the thermodynamic integration, thus showing that the two
      approaches give the same transition line. Finally, we determine the geometrical
      properties of the potential energy landscape, notably the T- and c dependence of
      the saddle index, and use these properties to obtain the dynamic transition
      temperature [Formula: see text]. The two temperatures [Formula: see text] and
      [Formula: see text] cross at a finite value of c and indicate the point at which
      the glass transition line ends. These findings are qualitatively consistent with
      the scenario proposed by the random first-order transition theory. 

PMID- 25976101
TI  - Correction for Stern et al., Evidence for indigenous nitrogen in sedimentary and
      aeolian deposits from the Curiosity rover investigations at Gale crater, Mars.

PMID- 25976102
TI  - The neuronal ceroid lipofuscinoses program: A translational research experience
      in Argentina.
AB  - BACKGROUND: The Argentinean program was initiated more than a decade ago as the
      first experience of systematic translational research focused on NCL in Latin
      America. The aim was to overcome misdiagnoses and underdiagnoses in the region.
      SUBJECTS: 216 NCL suspected individuals from 8 different countries and their
      direct family members. METHODS: Clinical assessment, enzyme testing, electron
      microscopy, and DNA screening. RESULTS AND DISCUSSION: 1) The study confirmed NCL
      disease in 122 subjects. Phenotypic studies comprised epileptic seizures and
      movement disorders, ophthalmology, neurophysiology, image analysis, rating
      scales, enzyme testing, and electron microscopy, carried out under a consensus
      algorithm; 2) DNA screening and validation of mutations in genes PPT1 (CLN1),
      TPP1 (CLN2), CLN3, CLN5, CLN6, MFSD8 (CLN7), and CLN8: characterization of
      variant types, novel/known mutations and polymorphisms; 3) Progress of the
      epidemiological picture in Latin America; and 4) NCL-like pathology studies in
      progress. The Translational Research Program was highly efficient in addressing
      the misdiagnosis/underdiagnosis in the NCL disorders. The study of "orphan
      diseases" in a public administrated hospital should be adopted by the health
      systems, as it positively impacts upon the family's quality of life, the
      collection of epidemiological data, and triggers research advances. This article
      is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid
      Lipofuscinoses (Batten Disease)".

PMID- 25976103
TI  - Validation of suitable reference genes for quantitative polymerase chain reaction
      analysis in rabbit bone marrow mesenchymal stem cell differentiation.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are considered as multipotent cells,
      representing a multi-lineage potential to differentiate into mesodermal lineages
      of mesenchymal tissues, including cartilage, bone, fat, muscle and tendon. Tissue
      engineering in BMSCs has made great advances in the regeneration of cartilage and
      bone defects. To uncover the mechanisms of the multipotent differentiation
      process, the molecular changes in gene expression profiles during chondrogenic
      and osteogenic differentiation need to be evaluated with reliable, accurate, fast
      and sensitive methods. Reverse transcription-quantitative polymerase chain
      reaction is a commonly used technology for analyzing gene expression, depending
      on an appropriate reference gene to normalize the errors. The commonly used
      reference genes vary, and no ideal and universal reference genes suitable for all
      conditions exist; therefore validation of the stability of gene expression is
      required. In the present study, three common statistical algorithms, geNorm,
      Normfinder and BestKeeper, were used to identify the expression stability of 12
      genes, and the target differentiation markers during the differentiation of BMSCs
      were evaluated accurately. Our results demonstrated that YWHAZ, PPIA and GAPDH
      were suitable as reference genes for chondrogenic differentiation, while RPL13a
      allowed an efficient normalization expression value of interest genes for
      osteogenic differentiation of BMSCs. By contrast, the most unstable reference
      genes were 18s rRNA, B2M and HPRT1 in all studies, and these should be avoided
      when investigating the differentiation of BMSCs. Our results demonstrate
      validation of the appropriate reference genes for accurate gene expression in
      chondrogenic and osteogenic differentiation of BMSCs.

PMID- 25976105
TI  - The role of structural disorder in cell cycle regulation, related clinical
      proteomics, disease development and drug targeting.
AB  - Understanding the molecular mechanisms of the regulation of cell cycle is a
      central issue in molecular cell biology, due to its fundamental role in the
      existence of cells. The regulatory circuits that make decisions on when a cell
      should divide are very complex and particularly subtly balanced in eukaryotes, in
      which the harmony of many different cells in an organism is essential for life.
      Several hundred proteins are involved in these processes, and a great deal of
      studies attests that most of them have functionally relevant intrinsic structural
      disorder. Structural disorder imparts many functional advantages on these
      proteins, and we discuss it in detail that it is involved in all key steps from
      signaling through the cell membrane to regulating transcription of proteins that
      execute timely responses to an ever-changing environment. 

PMID- 25976106
TI  - A novel bio-degradable polymer stabilized Ag/TiO2 nanocomposites and their
      catalytic activity on reduction of methylene blue under natural sun light.
AB  - In the present work we defined a novel method of TiO2 doped silver nanocomposite
      synthesis and stabilization using bio-degradable polymers viz., chitosan (Cts)
      and polyethylene glycol (PEG). These polymers are used as reducing agents. The
      instant formation of AgNPs was analyzed by visual observation and UV-visible
      spectrophotometer. TiO2 nanoparticles doped at different concentrations viz.,
      0.03, 0.06 and 0.09mM on PEG/Cts stabilized silver (0.04wt%) were successfully
      synthesized. This study presents a simple route for the in situ synthesis of both
      metal and polymer confined within the nanomaterial, producing ternary hybrid
      inorganic-organic nanomaterials. The results reveal that they have higher
      photocatalytic efficiencies under natural sun light. The synthesized TiO2 doped
      Ag nanocomposites (NCs) were characterized by SEM/EDS, TEM, XRD, FTIR and DLS
      with zeta potential. The stability of Ag/TiO2 nanocomposite is due to the high
      negative values of zeta potential and capping of constituents present in the
      biodegradable polymer which is evident from zeta potential and FT-IR studies. The
      XRD and EDS pattern of synthesized Ag/TiO2 NCs showed their crystalline
      structure, with face centered cubic geometry oriented in (111) plane. AFM and DLS
      studies revealed that the diameter of stable Ag/TiO2 NCs was approximately 35nm.
      Moreover the catalytic activity of synthesize Ag/TiO2 NCs in the reduction of
      methylene blue was studied by UV-visible spectrophotometer. The synthesized
      Ag/TiO2 NCs are observed to have a good catalytic activity on the reduction of
      methylene blue by bio-degradable which is confirmed by the decrease in absorbance
      maximum value of methylene blue with respect to time using UV-vis
      spectrophotometer. The significant enhancement in the photocatalytic activity of
      Ag/TiO2 nanocomposites under sun light irradiation can be ascribed to the effect
      of noble metal Ag by acting as electron traps in TiO2 band gap. 

PMID- 25976104
TI  - Genome-wide identification of MAPK, MAPKK, and MAPKKK gene families and
      transcriptional profiling analysis during development and stress response in
      cucumber.
AB  - BACKGROUND: The mitogen-activated protein kinase (MAPK) cascade consists of three
      types of reversibly phosphorylated kinases, namely, MAPK, MAPK kinase
      (MAPKK/MEK), and MAPK kinase kinase (MAPKKK/MEKK), playing important roles in
      plant growth, development, and defense response. The MAPK cascade genes have been
      investigated in detail in model plants, including Arabidopsis, rice, and tomato,
      but poorly characterized in cucumber (Cucumis sativus L.), a major popular
      vegetable in Cucurbitaceae crops, which is highly susceptible to environmental
      stress and pathogen attack. RESULTS: A genome-wide analysis revealed the presence
      of at least 14 MAPKs, 6 MAPKKs, and 59 MAPKKKs in the cucumber genome.
      Phylogenetic analyses classified all the CsMAPK and CsMAPKK genes into four
      groups, whereas the CsMAPKKK genes were grouped into the MEKK, RAF, and ZIK
      subfamilies. The expansion of these three gene families was mainly contributed by
      segmental duplication events. Furthermore, the ratios of non-synonymous
      substitution rates (Ka) and synonymous substitution rates (Ks) implied that the
      duplicated gene pairs had experienced strong purifying selection. Real-time PCR
      analysis demonstrated that some MAPK, MAPKK and MAPKKK genes are preferentially
      expressed in specific organs or tissues. Moreover, the expression levels of most
      of these genes significantly changed under heat, cold, drought, and
      Pseudoperonospora cubensis treatments. Exposure to abscisic acid and jasmonic
      acid markedly affected the expression levels of these genes, thereby implying
      that they may play important roles in the plant hormone network. CONCLUSION: A
      comprehensive genome-wide analysis of gene structure, chromosomal distribution,
      and evolutionary relationship of MAPK cascade genes in cucumber are present here.
      Further expression analysis revealed that these genes were involved in important
      signaling pathways for biotic and abiotic stress responses in cucumber, as well
      as the response to plant hormones. Our first systematic description of the MAPK,
      MAPKK, and MAPKKK families in cucumber will help to elucidate their biological
      roles in plant.

PMID- 25976107
TI  - Oral cavity and oropharyngeal cancer incidence trends and disparities in the
      United States: 2000-2010.
AB  - BACKGROUND: Changes in the incidence of oral cancer based on anatomic location
      and demographic factors over time have been reported in the United States. The
      purpose of this study was to use recent data to examine oral cancer incidence
      trends and disparities by demographic factors and anatomic location. METHODS:
      Surveillance, Epidemiology, and End Results (SEER) incidence data from 2000 to
      2010 were used to characterize and analyze oral cancer incidence trends by
      anatomic region and subsite, age at diagnosis, gender, race/ethnicity, and stage
      at diagnosis. Poisson regression was used to compare incidence risk by select
      demographic factors. RESULTS: About 75,468 incident oral cancer cases were
      diagnosed from 2000 to 2010. The tonsil was the most frequently diagnosed
      anatomic subsite (23.1%) and the subsite with the greatest contribution to the
      overall, age-standardized cumulative incidence rate of 8.4 cases per 100,000 (95%
      confidence interval (CI): 8.3, 8.4). An increasing incidence trend was observed
      for cancers in the oropharyngeal region, in contrast to a decreasing trend seen
      in the oral cavity region. In the Poisson regression model, all race/ethnicity
      groups showed a lower incidence risk relative to whites for oral cavity and
      oropharyngeal cancer, and white males displayed the highest incidence rate of all
      race/ethnicity-gender groups during the study period (14.1 per 100,000; 95% CI:
      14.0, 14.2). CONCLUSIONS: This study's epidemiological findings are especially
      important for oral health care providers, patient education, and the
      identification of risk profiles associated with oral cancer. The distinct
      epidemiological trends of oral cavity and oropharyngeal cancers dictate that oral
      cancer can no longer be viewed as a discrete entity. Oral health providers should
      have a strong understanding of the different risk factors associated with oral
      cavity and oropharyngeal cancers and educate their patients accordingly.

PMID- 25976108
TI  - Bortezomib plus CHOP for the treatment of HIV-associated plasmablastic lymphoma:
      clinical experience in three patients.

PMID- 25976109
TI  - Post-transplant lymphoproliferative disorder in adult renal transplant
      recipients: survival and prognosis.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a rare, serious
      complication following solid organ transplantation, with an incidence of 2.6
      cases per 1000 patient years. Optimal treatment strategies and risk
      stratifications specific to kidney transplantation are lacking and PTLD mortality
      remains high. This study investigated survival and prognosis in 89 cases of PTLD
      presenting over 44 years at Manchester Royal Infirmary. Patient survival
      following diagnosis was 72% at 6 months, 67% at 1 year and 54% at 3 years. In
      multivariate analysis, a poorer 3 year survival was associated with acute kidney
      injury at diagnosis (p = 0.0001), impaired renal function (p = 0.04), early onset
      (p = 0.02), T cell disease (p = 0.02) and previous treatment with anti-thymocyte
      globulin (p = 0.04). The inclusion of graft function adds prognostic value to
      risk stratification and should be explored further. Strategies to improve
      survival should include timing and choice of immuno-chemotherapy, preparation for
      dialysis and aggressive surveillance for sepsis and treatment toxicity.

PMID- 25976110
TI  - Chlorophyllin-M: A new substance for photodynamic therapy in the retina and
      choroid.
AB  - BACKGROUND AND OBJECTIVE: Chlorophyllin-M is a new chlorophyll-based derivative
      photosensitive compound developed by our research group with easy laboratorial
      synthesis and ideal properties for photodynamic therapy (PDT). It is intended for
      clinical treatments with simple and low cost techniques and reagents. The
      objective of this study is to evaluate if intravenous chlorophyllin-M is able to
      deliver a photosensitizer to rabbit retina and rabbit choroid and promote PDT
      after ocular irradiation with a 660 nm LASER. METHODS: This is a pre-clinical
      study. Ten eyes of five pigmented Californian rabbits were included in the study.
      The right eyes served as the treatment group, and the left eyes served as the
      control group. All eyes had been ophthalmologically evaluated and were considered
      normal. RESULTS: Ophthalmic exam with anterior biomicroscopy, dilated fundus
      examination, and fluorescein angiography after the LASER procedure revealed
      normal anterior segment, retinal and choroid vessels occlusion, lumen narrowing,
      and capillary non-perfusion in the treated areas, indicating that PDT was
      successful in the treatment eyes group. CONCLUSION: The results of this pre
      clinical study encourage future studies with this new compound. Chlorophyllin-M
      may become a new cost-effective agent in the retinal therapeutic arsenal.

PMID- 25976111
TI  - The impact of Parkinson's disease and subthalamic deep brain stimulation on
      reward processing.
AB  - BACKGROUND: Due to its position in cortico-subthalamic and cortico-striatal
      pathways, the subthalamic nucleus (STN) is considered to play a crucial role not
      only in motor, but also in cognitive and motivational functions. In the present
      study we aimed to characterize how different aspects of reward processing are
      affected by disease and deep brain stimulation of the STN (DBS-STN) in patients
      with idiopathic Parkinson's disease (PD). METHODS: We compared 33 PD patients
      treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33
      PD patients without DBS, but optimized pharmacological treatment and 34 age
      matched healthy controls. We then investigated DBS-STN effects using a
      postoperative stimulation-on/ -off design. The task set included a delay
      discounting task, a task to assess changes in incentive salience attribution, and
      the Iowa Gambling Task. RESULTS: The presence of PD was associated with increased
      incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN
      increased risky choices in the Iowa Gambling Task under DBS-on condition, but did
      not further affect incentive salience attribution or the evaluation of delayed
      rewards. CONCLUSION: Findings indicate that acute DBS-STN affects specific
      aspects of reward processing, including the weighting of gains and losses, while
      larger-scale effects of disease or medication are predominant in others reward
      related functions.

PMID- 25976112
TI  - Effect of Conjugated Linoleic Acid on Boar Semen Quality After Long-term
      Refrigeration at 17 degrees C.
AB  - In this study, the effect of conjugated linoleic acid (10 trans, 12 cis) (CLA) on
      refrigerated boar sperm quality parameters up to 14 days at 17 degrees C was
      assessed. Semen was extended in Androhep and divided into four treatments
      supplemented with CLA (25, 50, 100 and 200 MUm) and control group, then kept for
      2 h at 22 degrees C. Afterwards an aliquot of each treatment was removed, and
      mitochondrial activity, viability, lipid membrane peroxidation (LPO) and
      stability of the sperm plasma membrane were assessed by flow cytometry. The
      remaining extended semen was maintained at 17 degrees C until 336 h, repeating
      the same analysis every 48 h. Regarding percentage of live spermatozoa, no
      statistical differences were observed among treatments up to 96 h. After this
      time, viability decreased significantly (p < 0.05) for CLA concentrations of 100
      and 200 MUm. Despite these results, there was an individual response to CLA.
      Although in the control group, the boar A presented better results when compared
      with the other boars, especially at concentrations of 50 and 100 MUm boar B
      showed significantly higher results (p < 0.05). Supplementation with CLA improved
      (p < 0.05) LPO, but not the mitochondrial membrane potential of sperm. The
      highest two CLA concentrations showed to be toxic for sperm as all results were
      lower than the observed for the control. In conclusion, CLA at 50 MUm seems to be
      an efficient concentration for reducing the oxidative stress, decreasing LPO,
      maintaining viability, membrane stability and mitochondrial potential on
      refrigerated boar spermatozoa. 

PMID- 25976113
TI  - PsHint1, associated with the G-protein alpha subunit PsGPA1, is required for the
      chemotaxis and pathogenicity of Phytophthora sojae.
AB  - Zoospore chemotaxis to soybean isoflavones is essential in the early stages of
      infection by the oomycete pathogen Phytophthora sojae. Previously, we have
      identified a G-protein alpha subunit encoded by PsGPA1 which regulates the
      chemotaxis and pathogenicity of P. sojae. In the present study, we used affinity
      purification to identify PsGPA1-interacting proteins, including PsHint1, a
      histidine triad (HIT) domain-containing protein orthologous to human HIT
      nucleotide-binding protein 1 (HINT1). PsHint1 interacted with both the guanosine
      triphosphate (GTP)- and guanosine diphosphate (GDP)-bound forms of PsGPA1. An
      analysis of the gene-silenced transformants revealed that PsHint1 was involved in
      the chemotropic response of zoospores to the isoflavone daidzein. During
      interaction with a susceptible soybean cultivar, PsHint1-silenced transformants
      displayed significantly reduced infectious hyphal extension and caused a strong
      cell death in plants. In addition, the transformants displayed defective cyst
      germination, forming abnormal germ tubes that were highly branched and exhibited
      apical swelling. These results suggest that PsHint1 not only regulates chemotaxis
      by interacting with PsGPA1, but also participates in a Galpha-independent pathway
      involved in the pathogenicity of P. sojae. 

PMID- 25976114
TI  - [Reasons for the relevance of ultrasound performed by doctors family].

PMID- 25976115
TI  - [Virtual library of health sciences: reality and opportunity].

PMID- 25976116
TI  - Modes of action associated with uranium induced adverse effects in bone function
      and development.
AB  - Uranium, a naturally occurring element used in military and industrial
      applications, accumulates in the skeletal system of animals and humans. Evidence
      from animal and in-vitro studies demonstrates that uranium exposure is associated
      with alterations in normal bone functions. The available studies suggest that
      upon absorption uranium directly affects bone development and maintenance by
      inhibiting osteoblast differentiation and normal functions, and indirectly by
      disrupting renal production of Vitamin D. Animal studies also provide evidence
      for increased susceptibility to uranium-induced bone toxicity during early life
      stages. The objective of this review is to provide a summary of uranium-induced
      bone toxicity and the potential mechanisms by which uranium can interfere with
      bone development and promote fragility. Since normal Vitamin D production and
      osteoblast functions are essential for bone growth and maintenance, young
      individuals and the elderly may represent potentially susceptible populations to
      uranium-induced bone damage. 

PMID- 25976117
TI  - Improving coronary artery bypass graft durability: use of the external saphenous
      vein graft support.
AB  - Coronary bypass grafting remains the best option for patients suffering from
      multivessel coronary artery disease, and the saphenous vein is used as an
      additional conduit for multiple complete revascularizations. However, the long
      term vein graft durability is poor, with almost 75% of occluded grafts after 10
      years. To improve the durability, the concept of an external supportive structure
      was successfully developed during the last years: the eSVS Mesh device (Kips Bay
      Medical) is an external support for vein graft made of weft-knitted nitinol wire
      into a tubular form with an approximate length of 24 cm and available in three
      diameters (3.5, 4.0 and 4.5 mm). The device is placed over the outer wall of the
      vein and carefully deployed to cover the full length of the graft. The mesh is
      flexible for full adaptability to the heart anatomy and is intended to prevent
      kinking and dilatation of the vein in addition to suppressing the intima
      hyperplasia induced by the systemic blood pressure. The device is designed to
      reduce the vein diameter of about 15-20% at most to prevent the vein radial
      expansion induced by the arterial blood pressure, and the intima hyperplasia
      leading to the graft failure. We describe the surgical technique for preparing
      the vein graft with the external saphenous vein graft support (eSVS Mesh) and we
      share our preliminary clinical results.

PMID- 25976118
TI  - Erratum to: Salvage of failed hip osteosynthesis for fractures with modular hip
      prosthesis.

PMID- 25976119
TI  - Erratum to: enhancement of holding strength of cannulated screw supported with
      PMMA: a biomechanical study on femoral head.

PMID- 25976120
TI  - Barbed versus standard sutures in total knee arthroplasty: a meta-analysis.
AB  - INTRODUCTION: The use of barbed sutures in various surgical specialities has
      shown lower operative time and equivalent wound complications. Use of barbed
      suture in total knee arthroplasty is still at nascent stage with only few studies
      comparing it with the standard closure techniques. The purpose of this review was
      to appraise the clinical outcomes of barbed suture use in closure of total knee
      arthroplasty. METHODS: We searched the Cochrane library, PubMed and EMBASE up to
      December 2014 for clinical trials comparing the outcomes of closure of total knee
      arthroplasty with barbed sutures versus standard sutures. When there was no high
      heterogeneity, we used a fixed effects model. Dichotomous variables were
      presented as risk ratios (RRs) with 95 % confidence intervals (CIs), and
      continuous data were measured as measured differences with 95 % CIs. RESULTS:
      Five studies were included, with sample size ranging from 178 to 416. Fixed
      effect analysis showed that superficial infection was higher with barbed suture
      (RR 1.54, 95 % CI 0.36-2.59, P = 0.94). The barbed sutures have significantly
      lower closure time (MI -2.74, CI -3.06, -2.42, P < 0.00001). There was no
      difference in terms of deep infection, wound dehiscence, arthrofibrosis and total
      operative time. CONCLUSION: Our meta-analysis showed that the use of barbed
      sutures was associated with increased superficial infection rate and shorter
      estimated closure time. More RCTs are needed to examine the efficacy and safety
      of the barbed sutures.

PMID- 25976121
TI  - Biomechanical analysis of poly-L-lactic acid and titanium plates fixated for
      mandibular symphyseal fracture with a conservatively treated unilateral condylar
      fracture using the three-dimensional finite element method.
AB  - The purpose of this study was to investigate stress on poly-L-lactic acid (PLLA)
      plates with a thickness of 1.4 mm and titanium plates with a thickness of 1.0 and
      1.4 mm placed for mandibular symphyseal fractures with or without conservatively
      treated, unilateral condylar fractures using finite element analysis. The
      symphyseal fracture region was defined by the following three conditions: the
      defect, the callus, and the contact condition. Stress on the plates was analyzed
      by an applying occlusal force of 478.1 N on the first molar of the non-condylar
      fracture side. In the model of isolated symphyseal fracture, the maximal stresses
      were below the material strength in all plate types and conditions. In the models
      with condylar fracture, the maximal stresses on these plates were much higher
      than those in the models of isolated symphyseal fracture, especially for the
      defect condition. Although the maximal stresses on all types of plates in the
      contact condition were below the material strengths, some of those in the defect
      condition were higher than these strengths. These results suggest that a PLLA
      plate can theoretically withstand stress under good reductions of symphyseal
      fractures, even for condylar fractures; however, both the PLLA plate and titanium
      miniplate may be at risk of fracture under poor reduction.

PMID- 25976122
TI  - Identification of anti-biofilm components in Withania somnifera and their effect
      on virulence of Streptococcus mutans biofilms.
AB  - AIMS: The aim of this study was to identify components of the Withania somnifera
      that could show anti-virulence activity against Streptococcus mutans biofilms.
      METHODS AND RESULTS: The anti-acidogenic activity of fractions separated from W.
      somnifera was compared, and then the most active anti-acidogenic fraction was
      chemically characterized using gas chromatography-mass spectroscopy. The effect
      of the identified components on the acidogenicity, aciduricity and extracellular
      polymeric substances (EPS) formation of S. mutans UA159 biofilms was evaluated.
      The change in accumulation and acidogenicity of S. mutans UA159 biofilms by
      periodic treatments (10 min per treatment) with the identified components was
      also investigated. Of the fractions, n-hexane fraction showed the strongest anti
      acidogenic activity and was mainly composed of palmitic, linoleic and oleic
      acids. Of the identified components, linoleic and oleic acids strongly affected
      the acid production rate, F-ATPase activity and EPS formation of the biofilms.
      Periodic treatment with linoleic and oleic acids during biofilm formation also
      inhibited the biofilm accumulation and acid production rate of the biofilms
      without killing the biofilm bacteria. CONCLUSIONS: These results suggest that
      linoleic and oleic acids may be effective agents for restraining virulence of S.
      mutans biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Linoleic and oleic acids
      may be promising agents for controlling virulence of cariogenic biofilms and
      subsequent dental caries formation.

PMID- 25976124
TI  - Polyelectrolyte multilayer coatings for the separation of proteins by capillary
      electrophoresis: Influence of polyelectrolyte nature and multilayer crosslinking.
AB  - The present work aims at studying the influence of the nature of the
      polyelectrolytes used in successive multiple ionic polymers on the performances
      of protein separation in acetic acid volatile background electrolyte. A broad
      library of polyelectrolyte multilayers was compared on the basis of 9 different
      weak/strong polyanions and 8 different weak/strong polycations. More than 20
      couples of different polyelectrolytes were investigated. The separation
      efficiencies (expressed as the N/l ratio, where N is the plate number and l is
      the capillary effective length) were systematically compared for the separation
      of a protein test mixture. The coating stability was evaluated by the relative
      standard deviation of the migration times. For weak polyelectrolyte multilayers,
      the influence of the polymer crosslinking on the coating stability and separation
      efficiency has been studied. Intra-day repeatability of 100 successive runs, and
      capillary-to-capillary reproducibility were tested on coatings of each category
      (crosslinked and non crosslinked). The main (not obvious) result rising from this
      study is that the nature of the polyanion constituting the multilayers is of
      primary importance for the performance in terms of separation efficiency and
      stability, even when the mulilayers finish with a polycation. 

PMID- 25976125
TI  - Accuracy verification of surface energy components measured by inverse gas
      chromatography.
AB  - Inverse gas chromatography (IGC) measures the retention times of probes which are
      then used to calculate the surface properties of solids. No method is available
      to verify how much the measured values are close to their accurate values.
      According to the chromatographic adhesion law, the accurate determination of the
      dispersive retention factor (K(a)(CH2)) is a necessary prerequisite to obtain
      accurate surface components. Employing two equations in this paper,
      %DeltagammaS(d), which is the percentage deviation of dispersive component
      (gammaS(d)) from its accurate value (gammaS0(d)), was correlated firstly to
      %CV(ln K(a)(CH2)), the percentage coefficient of variation of ln K(a)(CH2), and
      secondly to FEK(a)(CH2), the factor error of K(a)(CH2), via two linear equations.
      The first equation is to outline the upper and lower limits of the uncertainty
      range of gammaS0(d), and the second equation is to estimate gammaS0(d). To
      minimize the uncertainty range of gammaS0(d) to less than +/-5%, %CV(ln
      K(a)(CH2)) should be less than 0.7%. Then considering the sign of FEK(a)(CH2)
      narrows the uncertainty range to either its upper or lower half.

PMID- 25976123
TI  - Black tea protects against hypertension-associated endothelial dysfunction
      through alleviation of endoplasmic reticulum stress.
AB  - Hypertensive patients have been found to be associated with elevated levels of
      homocysteine, known as hyperhomocysteinemia. Homocysteine (Hcy) can induce
      endoplasmic reticulum (ER) stress in endothelial cells. This study aims to
      investigate whether black tea (BT) protects against hypertension-associated
      endothelial dysfunction through alleviation of ER stress. Rat aortae and cultured
      rat aortic endothelial cells were treated with Hcy, BT extract, and theaflavin
      3,3'-digallate (TF3). Male Sprague Dawley rats were infused with angiotensin II
      (Ang II) to induce hypertension and orally administrated with BT extract at 15
      mg/kg/day for 2 weeks. Hcy impaired endothelium-dependent relaxations of rat
      aortae and led to ER stress in endothelial cells, which were ameliorated by co
      incubation of BT extract and TF3. The blood pressure of Ang II-infused rats and
      plasma Hcy level were normalized by BT consumption. Impaired endothelium
      dependent relaxations in renal arteries, carotid arteries and aortae, and flow
      mediated dilatations in third-order mesenteric resistance arteries were improved.
      Elevations of ER stress markers and ROS level, plus down-regulation of Hcy
      metabolic enzymes in aortae from Ang II-infused rats were prevented by BT
      treatment. Our data reveal the novel cardiovascular benefits of BT in
      ameliorating vascular dysfunctions, providing insight into developing BT into
      beneficial dietary supplements in hypertensive patients. 

PMID- 25976127
TI  - On the applicability of comprehensive two-dimensional gas chromatography combined
      with a fast-scanning quadrupole mass spectrometer for untargeted large-scale
      metabolomics.
AB  - Comprehensive two-dimensional gas chromatography mass spectrometry (GC*GC-MS)
      offers excellent chromatographic separation performance and superior sensitivity.
      As such, it is eminently suitable for the analysis of complex biological samples.
      The applicability of a GC*GC instrument equipped with a fast-scanning qMS
      detector for large-scale untargeted metabolome analyses was investigated. We
      optimized the dimensions of an apolar*medium-polar column combination in order to
      meet detector requirements and to compromise between separation performance and
      analysis time. The final method enabled a sufficient separation (R>=1.2 or
      higher) of approx. 90% of all analytes detected in urine within less than 1h.
      Using the qMS at maximum scan speed (20,000u/s) and choosing a scan range of m/z
      60-550, a data acquisition frequency of 33Hz and usually at least 10-13 data
      points per (2)D peak above the baseline were achieved. Peak area as well as peak
      height could thus be determined precisely (mean RSD 2.5%). Spectral skewing was
      limited regarding the data points covering the upper peak half. As a consequence,
      peak apex spectra could be used for the alignment of analytes in different
      samples. The linear dynamic range was 1-2.5 orders of magnitude, depending on the
      analyte. In addition, the slow transition into saturation beyond the linear
      dynamic range made it possible to exploit an extended "working range" for
      relative quantification. Long-term stability of the system was demonstrated by
      the analysis of more than 300 human urine study samples for which detailed
      repeatability and intermediate precision data are provided. In summary, the GC*GC
      qMS system proved to be applicable for untargeted large scale metabolome
      analyses. 

PMID- 25976126
TI  - Fabrication of chiral amino acid ionic liquid modified magnetic multifunctional
      nanospheres for centrifugal chiral chromatography separation of racemates.
AB  - As the rapid development of nanotechnology, the magnetic nanospheres modified
      with special chiral selective ligands show a great potentiality in enantiomeric
      separation. In this study, magnetic nanospheres modified with task-specific
      chiral ionic liquid were designed for the separation of chiral amino acids. These
      modified magnetic nanospheres were effective in a direct chiral separation of
      five racemic amino acids (D- and L-cysteine, D- and L-arginine, D- and L-leucine,
      D- and L-glutamine and D- and L-tryptophan). Furthermore, a new online method for
      complete separation of the enantiomers via the magnetic nanospheres was
      established with centrifugal chiral chromatography using a spiral tube assembly
      mounted on a type-J coil planet centrifuge. One kind of chiral compounds, D- and
      L-tryptophan was resolved well using this method. These results demonstrated that
      the modified nanospheres display a good chiral recognition ability, and can be
      used as a potential material for chiral separation of various racemates.

PMID- 25976128
TI  - Preparation and characterization of tentacle-type polymer stationary phase
      modified with graphene oxide for open-tubular capillary electrochromatography.
AB  - In this research, a novel organic polymer coated stationary phase modified with
      inorganic nanomaterial was prepared for open-tubular capillary
      electrochromatography (OT-CEC). The capillary was developed by covalent attaching
      graphene oxide (GO) onto the tentacle-type polymer chains grafted capillary which
      was derivatized with ammonium hydroxide. Scanning electron microscopy (SEM) and
      Raman spectroscopy provided evidences that the tentacle-type polymer and GO were
      coated to the capillary inner wall. This novel GO-polymer modified capillary
      column generated a strong and stable electroosmotic flow (EOF) from anode to
      cathode with the running electrolytes of pH ranging from 4.0 to 9.0, and showed
      excellent separation ability toward neutral small molecules, amino acids and
      ephedrine-pseudoephedrine isomers with resolution higher than 2.30 and column
      efficiency up to over 170,000 plates/m. The repeatabilities of the GO
      GMA@capillary were satisfying with relative standard deviations for intra-day and
      inter-day runs less than 3.27%, and column-to-column runs less than 7.49%.
      Additionally, the separation performance of GO-polymer modified capillary was
      compared with that of the polymer coated capillary and GO coated capillary.

PMID- 25976129
TI  - Study of perfusion changes in the optic disc of patients with fibromyalgia
      syndrome using new colorimetric analysis software.
AB  - PURPOSE: We measured the amount of hemoglobin at the optic nerve head of
      fibromyalgia (FM) patients using new colorimetric analysis software. We also
      investigated whether perfusion defects of the optic nerve head in patients with
      FM lead to tissue atrophy and corresponding retinal nerve fiber layer (RNFL)
      thinning measured by optical coherence tomography (OCT). METHODS: We recruited
      for this cross-sectional study 118 FM patients and 76 sex- and age-matched
      healthy controls. All subjects underwent a complete neuro-ophthalmologic
      examination, which also included visual field testing using the Spark strategy in
      an Easyfield perimeter, and OCT examinations using the Spectralis. One photograph
      of the optic disc was obtained using a CirrusTM Photo 800 multi-modality imager.
      We analyzed fundus photographs using Laguna ONhE software, a new method that
      allows hemoglobin levels to be measured at the optic nerve head. We compared
      hemoglobin percentages in different sectors of the nerve head and RNFL
      thicknesses between the two groups. RESULTS: Mean hemoglobin percentages and
      hemoglobin content in all optic nerve head sectors calculated by the Laguna ONhE
      program were significantly lower in FM patients than in healthy controls, and the
      main differences were detected in the outer ring, which corresponds with the
      neuroretinal rim. However, only the differences in the superotemporal RNFL were
      statistically significant. Correlations between the RNFL thickness and the
      percentage of hemoglobin in the different sectors were weak. CONCLUSION: Optic
      disc perfusion was decreased in patients with FM, especially within the
      neuroretinal rim, without clear involvement in the RNFL.

PMID- 25976130
TI  - [Treatment of diffuse retinal pigment epitheliopathies by antialdosterones or by
      photodynamic therapy].

PMID- 25976131
TI  - [Evaluation of corneal biomechanical properties in glaucoma and control patients
      by dynamic Scheimpflug corneal imaging technology].
AB  - PURPOSE: To compare corneal biomechanical properties measured with Corvis
      Scheimpflug technology (Corvis ST) between a group of patients with chronic open
      angle glaucoma and a group of control patients. DESIGN: Prospective observational
      case-control study. METHODS: This study enrolled 56 right eyes of 56 patients (G1
      [chronic open-angle glaucoma] n=37/G2 [control] n=19). Each patient underwent
      measurement of corneal biomechanical properties by dynamic Scheimpflug (Corvis
      ST) camera and the Ocular Response Analyser (ORA), then a measurement of
      intraocular pressure (IOP) by Goldmann applanation tonometry (GAT) and
      measurement of central corneal thickness (CCT) by optical coherence tomography
      during the same visit, by a single clinician. The parameters determined by Corvis
      ST are: Corvis IOP (IOP Corvis ST), the corneal deformation amplitude (CDA),
      corneal velocity, the time at highest concavity (TIME CONCAV), the lengths of
      applanation and their corresponding applanation time. Those studied by ORA are:
      compensated IOP (IOPcc), non-compensated IOL (IOPg), corneal hysteresis (CH) and
      corneal resistance factor (CRF). RESULTS: IOP measured on all patients by Corvis
      ST was positively correlated to GAT (Spearman r=0.569, P<0.001) and PIOcc
      (Spearman r=0.531, P<0.001). After adjusting for age effect, CCT and GAT, the CDA
      was significantly lower in G1 than in G2, respectively 1.10 +/- 0.12 mm and 1.15
      +/- 0.10mm (P<0.001). The TIME CONCAV is significantly shorter in G1 than in G2,
      respectively 16.88 +/- 0.63 ms and 17.11 +/- 0.29 ms, P=0.029. CH was
      significantly lower in G1 (G1: 9.58 +/- 1.94 than G2: 10.89 +/- 2.16, P=0.026).
      CONCLUSIONS: This study showed differences in corneal biomechanical properties
      between glaucoma and control patients. The cornea of glaucoma patients appears
      less deformable.

PMID- 25976132
TI  - Bilateral enucleation avoided by excision with mitomycin C for bilateral
      infiltrating conjunctival squamous cell carcinoma in a girl with xeroderma
      pigmentosum.

PMID- 25976133
TI  - Genetic landscape of uveal melanoma.
AB  - Uveal melanoma is genetically one of the simplest malignant tumors in adults.
      Initiation of these tumors is dependent of an oncogenic mutation in the GNAQ or
      GNA11 genes present in almost all cases. The nature of second mutational events
      is of major interest as it monosomy 3, gain of 8q and BAP1 inactivation are
      associated with unfavorable prognosis while SF3BI or EIF1AX are of good
      prognosis. Despite their common lineage, cutaneous and uveal melanomas are
      distinct diseases, implicating different oncogenic pathways and contrasting
      mutational landscapes. Even if uveal melanoma is a simple tumor, it is also one
      of the deadliest tumors in adults. There is a major clinical need for drugs
      targeting either the downstream pathways of Galphaq and Galpha11 or the
      biological cell functions dysregulated by BAP1 loss of function. 

PMID- 25976134
TI  - [Prognosis of primary malignant tumors of the conjunctiva].
AB  - PURPOSE: To discuss possible factors that could influence the prognosis of
      primary malignant conjunctival tumors. PATIENTS AND METHODS: We retrospectively
      analyzed medical records of 79 patients followed for primary malignant
      conjunctival tumors between January 1997 and July 2011. RESULTS: The mean age at
      the time of diagnosis was 61.1 years; male/female ratio was 2.59. The mean tumor
      size was 13.9 mm. The histological type was invasive squamous cell carcinoma in
      43 cases (54.4%), epithelial dysplasia in 11 cases (13.9%), carcinoma in situ in
      7 cases, conjunctival malignant melanoma in 5 cases, conjunctival lymphoma in 4
      cases and other rare tumors in 9 cases. We performed an excisional biopsy with a
      safety margin in 89.8% of cases, associated with cryotherapy in 46.6% of cases.
      Enucleation was performed in two cases and orbital exenteration in 5 cases. We
      noted tumor recurrence in 33.3% of patients after an average period of 9.5
      months. Radiation therapy was indicated in 44 cases (55.7%). The mean follow-up
      of our patients was 42 months. Tumor recurrences were statistically associated
      with a history of xeroderma pigmentosum (P=0.012), a diagnostic delay more than
      11 months (P=0.001), caruncular location (P=0.004), tumor size greater than 10mm
      (P=0.044), scleral extension (P=0.011), initial treatment limited to excisional
      biopsy (P=0.033) and histopathologic involvement of the margin of the tumor
      resection (P=0.008). CONCLUSION: A better understanding of the prognostic factors
      of primary malignant conjunctival tumors is essential for management and may
      improve the prognosis of these tumors.

PMID- 25976135
TI  - [Principle of the useful field of view and normative data].
AB  - PURPOSE: The useful field of view is a test which takes into account the
      influence of patient attention during the evaluation of the visual field. This
      study aims to generate normative data for an adaptation of the useful field of
      view (UFOV) test. These normative data are essential to judge, in a clinical
      setting, whether patients' performance is normal or not across demographically
      similar peers, in order to advise whether or not to resume driving after a brain
      injury (traumatic brain injury, stroke or cerebral tumour). PATIENTS AND METHODS:
      This study examined demographic influences on an UFOV adaptation in a sample of
      52 control participants (17 males and 35 females, aged 19 to 69) with no prior
      ophthalmologic or neurologic history. This adaptation used three visual attention
      tasks. In a simple task (ST), the participant had to detect, as fast as (s)he
      could, a single target in a visual display; in a double task (DT,) (s)he had to
      detect both a central and a lateral target in a double task with visual
      distractions present on the screen. The number of missed targets and the time
      needed to detect them are measured. RESULTS: Time to detect target was found to
      differ by gender and by age. Men and young people (from 19 to 29 years) are
      faster at detecting central and lateral targets. However, no demographic
      influence was observed on the number of missed targets. CONCLUSIONS: A normative
      table for this French UFOV adaptation is provided. This will allow clinicians to
      compare patient performance with similar peers and may help in identifying
      persons who would benefit from training on a driving simulator or having a road
      test with a driving-school.

PMID- 25976136
TI  - Treatment of retinoblastoma: The Institut Curie experience on a series of 730
      patients (1995 to 2009).
AB  - INTRODUCTION: To describe the results of retinoblastoma treatment from 1995-2009
      in a single institution. MATERIAL AND METHODS: Retrospective review of the charts
      of patients treated for retinoblastoma. Clinical characteristics at diagnosis,
      treatments and outcomes in terms of survival and ocular preservation are
      described. RESULTS: During the study period 826 children were referred for
      retinoblastoma and 730 were managed in our institution. Four hundred and eleven
      children presented with unilateral retinoblastoma and 319 with bilateral
      retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of
      children, 10 children presented with second tumors, 11 children died (6 of tumor
      related causes). Of the 411 children with unilateral retinoblastoma enucleation
      was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted
      for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of
      eyes). Three hundred and nineteen patients presented with bilateral
      retinoblastoma. Three hundred and ten could be treated conservatively for at
      least one eye. Initial intravenous chemotherapy was necessary for 75% of them.
      Ocular preservation without external beam radiation was possible for 221 patients
      (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%:
      P<0.001). DISCUSSION: Management and treatment of retinoblastoma are complex,
      adapted to the extent of the disease. Survival is good. Enucleation is still
      required for extensive ocular disease, especially for unilateral patients.
      Intravenous chemotherapy allows good tumor control and eye preservation and
      decrease the need of EBR. CONCLUSIONS: Retinoblastoma treatment with intravenous
      chemotherapy and ocular adjuvant therapies is very effective on the local tumor
      control and eye preservation.

PMID- 25976137
TI  - The genetic basis of uveal melanoma.
AB  - Uveal melanoma (UM) is the most common intraocular malignancy in adults with an
      incidence of about 1/100,000 new cases per year in the Western world. Risk
      factors are having a light skin, blond hair and blue eyes. As some UM patients
      have a young age at diagnosis or an affected family history for UM or other
      malignancies, there may be an underlying genetic basis. This review discusses
      known or suspected risk factors for UM, the cancer risk in UM patients and their
      family members, and the genes that have been reported to predispose to UM
      (germline mutations) and tumor development (somatic mutations). 

PMID- 25976138
TI  - [Invasive conjunctival squamous cell carcinoma after excision of a tumor
      simulating a pterygium].

PMID- 25976139
TI  - [Scleromalacia perforans secondary to ankylosing spondylitis: A case report].

PMID- 25976140
TI  - [Intraocular lymphoma associated with primary malignant lymphoma of the central
      nervous system: Seven-year experience of a tertiary center].
AB  - INTRODUCTION: Primary intraocular lymphoma (PIOL), associated with primary
      central nervous system lymphoma (PCNSL), is a rare malignancy disease. By way of
      a seven-year experience of a tertiary center, we discuss the presentation and we
      review the diagnostic and therapeutic modalities. OBSERVATIONS: We report six
      cases of PIOL associated with PCNSL. For all patients, the clinical presentation
      was a vitreoretinal syndrome. The diagnosis was histologically confirmed by
      vitreal sample or brain biopsy. Five patients developed a diffuse large B-cell
      lymphoma. Only one patient developed a T-cell lymphoma. The treatment consisted
      of conformational radiation therapy, systemic chemotherapy and intravitreal
      injections of methotrexate. The median survival after the diagnosis was 24
      months. DISCUSSION: PIOL, associated with PCNSL, is the most common type of
      ocular lymphoma. In most cases, ocular manifestations inaugurate the disease.
      PIOL is often fatal because of ultimate central nervous system presentation. The
      role of the ophthalmologist consists in early diagnosis. Typical clinical
      findings include vitroretinal tumor syndrome but can mascarade other eye
      pathologies. Diagnosis requires histology. The majority of PIOL is diffused large
      B-cell lymphoma. Decisions are made through multidisciplinary consultation. PIOL
      exhibits high responsiveness to methotrexate. CONCLUSION: Through a literature
      review and many illustrations, we discuss epidemiological, clinical,
      histological, radiological and treatment characteristics of PIOL associated with
      PCNSL.

PMID- 25976141
TI  - Histologic variability in solitary fibrous tumors reflects angiogenic and growth
      factor signaling pathway alterations.
AB  - This study aimed to evaluate expression of receptor tyrosine kinases, their
      ligands, and mutational status in solitary fibrous tumors, with correlation to
      histopathologic variants, tumor stage, and aggressive behavior.
      Immunohistochemical staining for PDGFalpha; PDGFbeta; PDGFR-alpha; PDGFR-beta;
      IGF1R; EGFR; VEGF; IGF2; c-Met; c-kit; c-erbB2; PTEN; and phosphorylated (p)AKT,
      pS6, and p4EBP1 was analyzed in 114 cases of solitary fibrous tumor using tissue
      microarray. Mutational analysis was performed using Sequenom MassARRAY-based
      platform. Multiple growth factors were overexpressed in most tumors, and
      increased numbers of overexpressed factors correlated with activation of the AKT
      pathway as measured by increased expression of p4EBP1(P = .0005). Compared to
      hypocellular tumors, localized hypercellular tumors were associated with high
      vascular endothelial growth factor (32% versus 8%; P = .008) and PDGFbeta (41%
      versus 13%; P = .008). Metastatic tumors more frequently overexpressed PDGFR
      alpha compared to localized tumors (75% versus 31%; P < .001). None of the
      factors examined had prognostic significance in primary tumors. Single-nucleotide
      polymorphisms involving MET were identified in 4 patients; these do not appear to
      drive tumor behavior and were not reflected in c-Met expression levels.
      Simultaneous overexpression of multiple growth factors is common in solitary
      fibrous tumors; variability in expression may contribute to tumor phenotype and
      aggressive behavior. 

PMID- 25976142
TI  - Pediatric surgical innovation. Preface.

PMID- 25976143
TI  - Biodesign process and culture to enable pediatric medical technology innovation.
AB  - Innovation is the process through which new scientific discoveries are developed
      and promoted from bench to bedside. In an effort to encourage young entrepreneurs
      in this area, Stanford Biodesign developed a medical device innovation training
      program focused on need-based innovation. The program focuses on teaching
      systematic evaluation of healthcare needs, invention, and concept development.
      This process can be applied to any field of medicine, including Pediatric
      Surgery. Similar training programs have gained traction throughout the United
      States and beyond. Equally important to process in the success of these programs
      is an institutional culture that supports transformative thinking. Key components
      of this culture include risk tolerance, patience, encouragement of creativity,
      management of conflict, and networking effects. 

PMID- 25976144
TI  - Challenges and climate of business environment and resources to support pediatric
      device development.
AB  - The incidence of pediatric disease conditions pales in comparison to adult
      disease. Consequently, many pediatric disorders are considered orphan diseases.
      Resources for the development of devices targeting orphan diseases are scarce and
      this poses a unique challenge to the development of pediatric devices. This
      article outlines these challenges and offers solutions. 

PMID- 25976145
TI  - Surgical innovation and quality assurance: Can we have both?
AB  - Innovation is the major force for progress in pediatric surgery. Most of the
      progress in surgery has evolved secondary to novel approaches developed by
      surgeons confronted with difficult pathologic conditions. Up to the present time,
      most surgical innovation has been practiced with few rules for guidance.
      Innovation to make surgical procedures more effective and less morbid is highly
      desirable. However, the absence of oversight has the potential to lead to
      unbridled human experimentation. The quality improvement movement in medicine is
      attempting to improve outcomes using evidence-based clinical pathways. Quality
      improvement aims to decrease the variation in therapeutic approaches by
      scientifically defining best practices. There is a significant potential for
      autonomous surgical innovators to clash with well-meaning proponents of quality
      improvement. A suggested remedy to encourage surgical innovators while protecting
      patients from unintended harm is for institutions to develop Surgical Innovation
      Committees to evaluate and give oversight to the early application of new
      techniques and devices. Scientific evaluation under the auspices of an IRB should
      follow when feasible. 

PMID- 25976146
TI  - Innovation in surgical technology and techniques: Challenges and ethical issues.
AB  - The pace of medical innovation continues to increase. The deployment of new
      technologies in surgery creates many ethical challenges including how to
      determine safety of the technology, what is the timing and process for deployment
      of a new technology, how are patients informed before undergoing a new technology
      or technique, how are the outcomes of a new technology evaluated and how are the
      responsibilities of individual patients and society at large balanced. Ethical
      considerations relevant to the implementation of ECMO and robotic surgery are
      explored to further discussion of how we can optimize the delicate balance
      between innovation and regulation. 

PMID- 25976147
TI  - Innovation in pediatric surgical education.
AB  - Pediatric surgical training in the United States remained basically unchanged
      from the model developed by Ladd and Gross in the 1930s until recently.
      Standardized curriculum and novel evaluation methods are now being implemented.
      Pediatric Surgical education is currently undergoing a transition to competency
      based evaluation and promotion. Unfortunately, there is little data on the
      efficacy of these changes. This presents an opportunity for further study of how
      we conduct training, and how we evaluate and promote our trainees. 

PMID- 25976148
TI  - Modern, multi-media, advances in surgical information.
AB  - The need for education does not end with residency. Practicing surgeons must find
      ways to stay current. The boom in new technologic developments may significantly
      enhance our methods of teaching through the use of new mutli-media. Here we will
      explore some of the muti-media innovations that have or may have the greatest
      impact on surgical education. Live, interactive, and online forums have proven to
      be effective new methods of bringing people together to discuss and learn new
      concepts in medicine. These forums allow physicians to interact with key opinion
      leaders and flatten knowledge sharing, so that everyone may have a voice. The
      dynamic, fast paced, and interactive format allows for screen-based learning to
      be engaging and interactive. Information is now available online in multiple
      formats that are continuously updated, so that information is no longer outdated
      by the time it is published in a textbook. Multi-media is now being used to
      disseminate content through, archived video, live video, as well as audiocasts.
      All of these are creating more modern ways for physicians to stay up-to-date
      either at home, in the office, or when mobile. Lastly, new advanced, interactive,
      technology can allow experts to assist less-experienced surgeons as "virtual
      partners" through telementoring. With telementoring, an expert can be virtually
      present while another surgeon is performing a complex, new, operation, and the
      expert can help with voice suggestions and on-screen telestration. Pediatric
      surgical education has made a giant leap thanks to new developments in multi
      media technology. 

PMID- 25976149
TI  - Trends in technical and team simulations: Challenging the status Quo of surgical
      training.
AB  - Traditional opportunistic and experiential surgical training can expose patients
      to excess risk of harm, particularly when new technology or surgical approaches
      are applied to highly complex operations. Declining birth rates, decreasing
      academic regionalization of complex neonatal procedures, duty hour restrictions,
      and the increasing need for highly specialized surgical skills all serve to
      further degrade the educational opportunities for surgical trainees. Even more
      concerning, practicing pediatric surgeons are also struggling with declines in
      neonatal surgical volumes, with fewer opportunities to maintain established
      cognitive, technical, and nontechnical skills in the operating room. In an effort
      to balance patient safety with a deeply rooted commitment to surgical education,
      surgical educators have developed a number of innovative educational strategies
      to achieve these goals. 

PMID- 25976150
TI  - The role of new information technology meeting the global need and gap of
      education in pediatric surgery.
AB  - Traditionally, pediatric surgical education consisted of exposure to patients,
      textbooks, lectures, team-based education, congresses, and workshops. Over the
      last decades, however, new information technology (IT) and the internet
      revolutionized the sharing of information and communication. IT has become
      relevant in particular for the younger generation of pediatric surgeons. Today,
      gaps in children's health and the quality of pediatric surgical education persist
      between countries and regions. Advances in health care are not shared equitably.
      The use of IT for resource libraries, teleconferences, virtual symposiums, and
      telementoring has great potential in closing this gap and meeting the global
      needs for pediatric surgical education. This article focuses on the potential
      role of IT in this respect.

PMID- 25976151
TI  - Innovating for quality and value: Utilizing national quality improvement programs
      to identify opportunities for responsible surgical innovation.
AB  - Innovation in surgical techniques, technology, and care processes are essential
      for improving the care and outcomes of surgical patients, including children. The
      time and cost associated with surgical innovation can be significant, and unless
      it leads to improvements in outcome at equivalent or lower costs, it adds little
      or no value from the perspective of the patients, and decreases the overall
      resources available to our already financially constrained healthcare system. The
      emergence of a safety and quality mandate in surgery, and the development of the
      American College of Surgeons National Surgical Quality Improvement Program
      (NSQIP) allow needs-based surgical care innovation which leads to value-based
      improvement in care. In addition to general and procedure-specific clinical
      outcomes, surgeons should consider the measurement of quality from the patients'
      perspective. To this end, the integration of validated Patient Reported Outcome
      Measures (PROMs) into actionable, benchmarked institutional outcomes reporting
      has the potential to facilitate quality improvement in process, treatment and
      technology that optimizes value for our patients and health system. 

PMID- 25976152
TI  - Patients as partners in innovation.
AB  - As the culture of medical practice has evolved, so has the relationship between
      the physician and patient. This is decidedly true with regards to the
      introduction of innovative therapies, especially in the surgical arena. A
      critical challenge is identifying and defining innovative therapy. Is the
      proposed treatment an incremental change, a research proposal, or more commonly
      someplace in between? This gray area creates a transition zone commonly referred
      to as innovative therapy. Given the complexities of the current landscape of
      innovation, innovation therapy committees may provide a mechanism to help to
      guide both physicians and patients through such difficult topics as the process
      of informed consent, managing conflicts of interest, and how to evaluate the
      outcomes of innovative therapies. As surgical innovation remains critical to the
      advancement of care, it must occur in a transparent partnership with patients,
      under the eye of guiding entities, aimed at ultimately improving outcomes and
      care. 

PMID- 25976153
TI  - The evolving identity, capacity, and capability of the future surgeon.
AB  - Technology has transformed surgery more within the last 30 years than the
      previous 2000 years of human history combined. These innovations have changed not
      only how the surgeon practices but have also altered the very essence of what it
      is to be a surgeon in the modern era. Beyond the industrial revolution, today's
      information revolution allows patients access to an abundance of easily
      accessible, unfiltered information which they can use to evaluate their surgical
      treatment, and truly participate in their personal care. We are entering yet
      another revolution specifically affecting surgeons, where the traditional
      surgical tools of our craft are becoming "smart." Intelligence in surgical tools
      and connectivity based on sensory data, processing, and analysis are enabling and
      enhancing a surgeon's capacity and capability. Given the tempo of change, within
      one generation the traditional role and identity of a surgeon will be fully
      transformed. In this article, the impact of the information revolution,
      technological advances combined with smart connectivity on the changing role of
      surgery will be considered.

PMID- 25976154
TI  - Serum IL-33 levels are increased in patients with psoriasis.
AB  - BACKGROUND: Interleukin (IL)-33 is a recently identified cytokine, which is a
      member of the IL-1 family and binds to a heterodimeric receptor comprising ST2
      (suppression of tumorigenicity 2) and IL-1 receptor accessory protein. Serum
      levels of IL-33 have been reported to be upregulated in various T helper
      (Th)1/Th17-mediated diseases, such as rheumatoid arthritis and inflammatory bowel
      disease. IL-33 expression is increased in lesional skin in patients with
      psoriasis, but serum levels in patients with psoriasis have not yet been studied.
      AIM: To study serum IL-33 levels in patients with psoriasis, a Th1/Th17-mediated
      skin disease, before and after anti-tumour necrosis factor (TNF)-alpha therapy.
      METHODS: Serum IL-33 levels were measured in patients with psoriasis vulgaris
      (PV), psoriatic arthritis (PsA) or pustular psoriasis (PP), and compared with
      those of healthy controls. Associations between serum IL-33 levels and serum TNF
      alpha, IL-6, vascular endothelial growth factor and C-reactive protein levels
      were also studied. In addition, the effect of IL-33 stimulation on IL-6, IL-8,
      TNF-alpha and VEGF secretion by human keratinocyte was analysed. RESULTS: Serum
      IL-33 levels in patients with PV, PsA and PP were significantly higher than those
      in healthy controls. Serum IL-33 levels correlated with serum TNF-alpha levels in
      patients with psoriasis, and decreased after anti-TNF-alpha therapy. IL-33
      stimulated IL-6 and IL-8 secretion by human keratinocytes. CONCLUSIONS: These
      results suggest that serum IL-33 levels generally reflect increased inflammation
      in patients with psoriasis.

PMID- 25976155
TI  - A novel multicolor immunostaining method using ethynyl deoxyuridine for analysis
      of in situ immunoproliferative response.
AB  - Immune responses are generally accompanied by antigen presentation and
      proliferation and differentiation of antigen-specific lymphocytes
      (immunoproliferation), but analysis of these events in situ on tissue sections is
      very difficult. We have developed a new method of simultaneous multicolor
      immunofluorescence staining for immunohistology and flow cytometry using a
      thymidine analogue, 5-ethynyl-2'-deoxyuridine (EdU). Because of the small size of
      azide dye using click chemistry and elimination of DNA denaturation steps, EdU
      staining allowed for immunofluorescence staining of at least four colors
      including two different markers on a single-cell surface, which is impossible
      with the standard 5-bromo-2'-deoxyuridine method. By using two rat models,
      successfully detected parameters were the cluster of differentiation antigens
      including phenotypic and functional markers of various immune cells,
      histocompatibility complex antigens, and even some nuclear transcription factors.
      Proliferating cells could be further sorted and used for RT-PCR analysis. This
      method thus enables functional in situ time-kinetic analysis of
      immunoproliferative responses in a distinct domain of the lymphoid organs, which
      are quantitatively confirmed by flow cytometry. 

PMID- 25976156
TI  - Fatal case of Herbaspirillum seropedicae bacteremia secondary to pneumonia in an
      end-stage renal disease patient with multiple myeloma.
AB  - Herbaspirillum spp. are rare causes of human infections associated primarily with
      bacteremia in cancer patients. We report the first fatal case of bacteremia
      secondary to pneumonia caused by Herbaspirillum seropedicae in a 65-year-old man
      with end-stage renal disease and multiple myeloma. 

PMID- 25976157
TI  - Offending profiles of individuals with autism spectrum disorder: A study of all
      individuals with autism spectrum disorder examined by the forensic psychiatric
      service in Norway between 2000 and 2010.
AB  - This study examined the characteristics of adults with autism spectrum disorder
      who have undergone a forensic examination and explored any relationships between
      the diagnosis and the offence. The reports described 41 men and 7 women. The
      autism spectrum disorder was diagnosed late (mean age: 25.3 years), and 22 of the
      48 cases were diagnosed with autism spectrum disorder for the first time by the
      forensic experts. The education level and employment status were low. Family
      networks were close, but social networks outside the family were limited. Co
      morbid diagnoses were common, and more than half of the group knew their victims.
      The examined individuals constitute a vulnerable and heterogeneous group, as do
      offenders within other diagnostic categories. Unlike most others who commit
      criminal acts, the majority of the individuals with autism spectrum disorder in
      this study showed no evidence of substance abuse, had a close relationship to
      their victims and were willing to confess to the accused crime. No clear
      association between the characteristics of autism spectrum disorder and the
      criminal act were identified, but in most cases, autism spectrum disorder
      characteristics, such as idiosyncratic comprehensions and obsessions appeared to
      be related to the motive for the offence. 

PMID- 25976158
TI  - How are they doing? Listening as fathers of children with autism spectrum
      disorder compare themselves to fathers of children who are typically developing.
AB  - The growing prevalence of autism spectrum disorder is accompanied by ongoing
      efforts to understand and support parents in the face of challenges related to
      their child's autism spectrum disorder. Although fathers are increasingly hands
      on in raising children, research focus on parenting children with autism spectrum
      disorder continues to be skewed toward experiences of mothers. Our purpose in
      this article is to contribute understandings of how fathers of children with
      autism spectrum disorder perceive themselves to be managing, and we undertake
      this by examining comparisons fathers of children with autism spectrum disorder
      make between their parenting experiences and experiences of fathers of typically
      developing children. A purposive sample of 28 fathers of children (aged 2-13
      years) with autism spectrum disorder living in an urban center in Western Canada
      participated in in-depth interviews about their parenting successes and
      challenges. We found fathers speak of universal fathering experiences yet
      articulate their own sense of loss and efforts to come to terms with
      unanticipated demands associated with autism spectrum disorder. Fathers of
      children with autism spectrum disorder feel "pangs of jealousy" toward fathers of
      typically developing children, yet they are keenly attentive to their own child's
      development and convey a sense of gratitude for their child's capabilities and
      personality amidst an appreciation for trials and triumphs of fathering in
      general and fathering a child with autism spectrum disorder in particular. 

PMID- 25976160
TI  - DNA methylation reprogramming during oogenesis and interference by reproductive
      technologies: Studies in mouse and bovine models.
AB  - The use of assisted reproductive technology (ART) to overcome fertility problems
      has continued to increase since the birth of the first baby conceived by ART over
      30 years ago. Similarly, embryo transfer is widely used as a mechanism to advance
      genetic gain in livestock. Despite repeated optimisation of ART treatments, pre-
      and postnatal outcomes remain compromised. Epigenetic mechanisms play a
      fundamental role in successful gametogenesis and development. The best studied of
      these is DNA methylation; the appropriate establishment of DNA methylation
      patterns in gametes and early embryos is essential for healthy development.
      Superovulation studies in the mouse indicate that specific ARTs are associated
      with normal imprinting establishment in oocytes, but abnormal imprinting
      maintenance in embryos. A similar limited impact of ART on oocytes has been
      reported in cattle, whereas the majority of embryo-focused studies have used
      cloned embryos, which do exhibit aberrant DNA methylation. The present review
      discusses the impact of ART on oocyte and embryo DNA methylation with regard to
      data available from mouse and bovine models. 

PMID- 25976159
TI  - Differential distribution of GABA and glycine terminals in the inferior
      colliculus of rat and mouse.
AB  - The inferior colliculus (IC), the midbrain component of the auditory pathway,
      integrates virtually all inputs from the auditory brainstem. These are a mixture
      of excitatory and inhibitory ascending inputs, and the inhibitory transmitters
      include both gamma-aminobutyric acid (GABA) and glycine (GLY). Although the
      presence of these inhibitory inputs is well established, their relative location
      in the IC is not, and there is little information on the mouse. Here, we study
      the distribution of glutamic acid decarboxylase (GAD)67 and GLY transporter 2
      (T2) in axonal terminals to better understand the relative contributions of these
      inputs. Large-scale mosaic composite images of immunohistochemistry sections of
      rat and mice were used to isolate the signals related to the concentrations of
      these axonal terminals in the tissue, and the ratio of GLYT2/GAD67 in each pixel
      was calculated. GLYT2 was seen only in the central nucleus of the IC (ICC),
      whereas GAD67 was seen throughout the IC. The map of the GAD67 and GLYT2 axonal
      distribution revealed a gradient that runs from ventrolateral to dorsomedial
      along the axis of the laminae of the ICC and perpendicular to the tonotopic axis.
      Although anatomically different, both the mouse and the rat had relatively more
      GAD67 dorsomedially in the ICC and relatively more GLYT2 ventrolaterally. This
      organization of GABA and GLY inputs may be related to functional zones with
      different properties in ICC that are based, in part, on different sets of
      inhibitory inputs to each zone.

PMID- 25976161
TI  - Early insights into the neurobiology of pain in sickle cell disease: A systematic
      review of the literature.
AB  - Novel insights into the neurobiology of sickle cell disease (SCD) pain have
      recently been discovered. We systematically reviewed the literature focusing on
      original research that examined the biology of pain in SCD and/or addressed
      assessment or treatment of neuropathic pain in SCD. This review of 15 articles
      that met inclusion criteria provides epidemiological, basic, and clinical data
      that support central and/or peripheral nervous system abnormalities likely
      contribute to sickle cell pain. Continued basic and clinical investigation into
      pain neurobiology is imperative to translate these discoveries into novel ways to
      assess and treat neuropathic pain and decrease patient suffering.

PMID- 25976163
TI  - Pulmonary Vein Stenosis After Minimally Invasive Stand-alone Surgical Ablation of
      Atrial Fibrillation.
AB  - We report a case of pulmonary vein stenosis following a standalone minimally
      invasive surgical ablation for atrial fibrillation. The etiology, diagnosis, and
      management of this complication are the subject of this review.

PMID- 25976162
TI  - CONSORT extension for reporting N-of-1 trials (CENT) 2015: Explanation and
      elaboration.

PMID- 25976164
TI  - Advances in theory and their application within the field of zeolite chemistry.
AB  - Zeolites are versatile and fascinating materials which are vital for a wide range
      of industries, due to their unique structural and chemical properties, which are
      the basis of applications in gas separation, ion exchange and catalysis. Given
      their economic impact, there is a powerful incentive for smart design of new
      materials with enhanced functionalities to obtain the best material for a given
      application. Over the last decades, theoretical modeling has matured to a level
      that model guided design has become within reach. Major hurdles have been
      overcome to reach this point and almost all contemporary methods in computational
      materials chemistry are actively used in the field of modeling zeolite chemistry
      and applications. Integration of complementary modeling approaches is necessary
      to obtain reliable predictions and rationalizations from theory. A close synergy
      between experimentalists and theoreticians has led to a deep understanding of the
      complexity of the system at hand, but also allowed the identification of
      shortcomings in current theoretical approaches. Inspired by the importance of
      zeolite characterization which can now be performed at the single atom and single
      molecule level from experiment, computational spectroscopy has grown in
      importance in the last decade. In this review most of the currently available
      modeling tools are introduced and illustrated on the most challenging problems in
      zeolite science. Directions for future model developments will be given. 

PMID- 25976167
TI  - Photocatalytic water disinfection by simple and low-cost monolithic and
      heterojunction ceramic wafers.
AB  - In this work, the photocatalytic disinfection of Escherichia coli (E. coli) using
      dual layer ceramic wafers, prepared by a simple and low-cost technique, was
      investigated. Heterojunction wafers were prepared by pressing TiO2 and WO3
      powders together into 2 layers within a single, self-supported monolith. Data
      modelling showed that the heterojunction wafers were able to sustain the
      formation of charged species (after an initial "charging" period). In comparison,
      a wafer made from pure TiO2 showed a less desirable bacterial inactivation
      profile in that the rate decreased with time (after being faster initially). The
      more favourable kinetics of the dual layer system was due to superior electron
      hole vectorial charge separation and an accumulation of charges beyond the
      initial illumination period. The results demonstrate the potential for developing
      simplified photocatalytic devices for rapid water disinfection. 

PMID- 25976166
TI  - A Kinase-Independent Function of c-Src Mediates p130Cas Phosphorylation at the
      Serine-639 Site in Pressure Overloaded Myocardium.
AB  - Early work in pressure overloaded (PO) myocardium shows that integrins mediate
      focal adhesion complex formation by recruiting the adaptor protein p130Cas (Cas)
      and nonreceptor tyrosine kinase c-Src. To explore c-Src role in Cas-associated
      changes during PO, we used a feline right ventricular in vivo PO model and a
      three-dimensional (3D) collagen-embedded adult cardiomyocyte in vitro model that
      utilizes a Gly-Arg-Gly-Asp-Ser (RGD) peptide for integrin stimulation. Cas showed
      slow electrophoretic mobility (band-shifting), recruitment to the cytoskeleton,
      and tyrosine phosphorylation at 165, 249, and 410 sites in both 48 h PO
      myocardium and 1 h RGD-stimulated cardiomyocytes. Adenoviral mediated expression
      of kinase inactive (negative) c-Src mutant with intact scaffold domains (KN-Src)
      in cardiomyocytes did not block the RGD stimulated changes in Cas. Furthermore,
      expression of KN-Src or kinase active c-Src mutant with intact scaffold function
      (A-Src) in two-dimensionally (2D) cultured cardiomyocytes was sufficient to cause
      Cas band-shifting, although tyrosine phosphorylation required A-Src. These data
      indicate that c-Src's adaptor function, but not its kinase function, is required
      for a serine/threonine specific phosphorylation(s) responsible for Cas band
      shifting. To explore this possibility, Chinese hamster ovary cells that stably
      express Cas were infected with either beta-gal or KN-Src adenoviruses and used
      for Cas immunoprecipitation combined with mass spectrometry analysis. In the KN
      Src expressing cells, Cas showed phosphorylation at the serine-639 (human
      numbering) site. A polyclonal antibody raised against phospho-serine-639 detected
      Cas phosphorylation in 24-48 h PO myocardium. Our studies indicate that c-Src's
      adaptor function mediates serine-639 phosphorylation of Cas during integrin
      activation in PO myocardium.

PMID- 25976165
TI  - Potentiation of temozolomide antitumor effect by purine receptor ligands able to
      restrain the in vitro growth of human glioblastoma stem cells.
AB  - Glioblastoma multiforme (GBM), the most common and aggressive brain tumor in
      humans, comprises a population of stem-like cells (GSCs) that are currently
      investigated as potential target for GBM therapy. Here, we used GSCs isolated
      from three different GBM surgical specimens to examine the antitumor activity of
      purines. Cultured GSCs expressed either metabotropic adenosine P1 and ATP P2Y
      receptors or ionotropic P2X7 receptors. GSC exposure for 48 h to 10-150 MUM ATP,
      P2R ligand, or to ADPbetaS or MRS2365, P2Y1R agonists, enhanced cell expansion.
      This effect was counteracted by the PY1R antagonist MRS2500. In contrast, 48-h
      treatment with higher doses of ATP or UTP, which binds to P2Y2/4R, or 2'(3')-O-(4
      benzoylbenzoyl)-ATP (Bz-ATP), P2X7R agonist, decreased GSC proliferation. Such a
      reduction was due to apoptotic or necrotic cell death but mostly to growth
      arrest. Accordingly, cell regrowth and secondary neurosphere formation were
      observed 2 weeks after the end of treatment. Suramin, nonselective P2R
      antagonist, MRS1220 or AZ11645373, selective A3R or P2X7R antagonists,
      respectively, counteracted ATP antiproliferative effects. AZ11645373 also
      abolished the inhibitory effect of Bz-ATP low doses on GSC growth. These findings
      provide important clues on the anticancer potential of ligands for A3R, P2Y1R,
      and P2X7R, which are involved in the GSC growth control. Interestingly, ATP and
      BzATP potentiated the cytotoxicity of temozolomide (TMZ), currently used for GBM
      therapy, enabling it to cause a greater and long-lasting inhibitory effect on GSC
      duplication when readded to cells previously treated with purine nucleotides plus
      TMZ. These are the first findings identifying purine nucleotides as able to
      enhance TMZ antitumor efficacy and might have an immediate translational impact.

PMID- 25976168
TI  - Bioeffects of micron-size magnesium particles on inflammatory cells and bone
      turnover in vivo and in vitro.
AB  - Magnesium (Mg) is a promising biodegradable metal offering many potential
      advantages over current scaffold technologies. Many studies have reported on the
      corrosion characteristics the Mg and its bioeffects in vitro and in vivo, but
      there are few studies on the biological effects of the corrosive products of Mg -
      the micron-size Mg particles (MgMPs). In this study, the effects of size-selected
      commercial MgMPs on bone turnover and macrophages were investigated in vivo and
      in vitro. We found that MgMPs were susceptible to engulfment by macrophages,
      leading to cell lysis, likely resulting from H2 gas production. We also found
      that the inflammatory cytokines IL-1, IL-6, and TNF-alpha were induced more
      strongly by titanium particles (TiMPs) group than by either MgMPs or control.
      Examination of the expression of bone remodeling markers revealed that MgMPs are
      beneficial for bone regeneration. Micro-CT scanning indicated that, 30 days
      postimplantation, unlike TiMPs, MgMPs had no adverse effect on either bone
      quality or quantity. We have investigated the bioeffects of micron-size MgMPs in
      vivo and in vitro, and our results indicate that MgMPs may promote bone
      regeneration without inducing inflammation. (c) 2015 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 104B: 923-931, 2016.

PMID- 25976169
TI  - Synergistic Effects of [Ile7]Surfactin Homologues with Bacillomycin D in
      Suppression of Gray Mold Disease by Bacillus amyloliquefaciens Biocontrol Strain
      SD-32.
AB  - We previously reported that Bacillus amyloliquefaciens biocontrol strain SD-32
      produces powerful antifungal lipopeptides, C17 bacillomycin D homologues. In the
      course of the investigation we found that the antifungal activity of the culture
      supernatant of this bacterium was not ascribed exclusively to bacillomycin D. We
      attempted to identify metabolites other than bacillomycin D to gain insight into
      the mechanism for the biocontrol by this bacterium. After purifying the fractions
      of the culture supernatant exhibiting synergistic activity with bacillomycin D,
      we isolated two new cyclic lipodepsipeptides, anteiso-C13 and iso-C13
      [Ile(7)]surfactins, together with three known [Ile(7)]surfactins. Interestingly,
      [Ile(7)]surfactins showed synergistic activities with bacillomycin D to gray mold
      disease on cucumber leaves but not to Botrytis cinerea itself in vitro,
      suggesting that the synergistic effects might be on infection processes of the
      fungus. Actually, we observed that they did not show synergistic actions on
      conidial germination or mycelial growth of B. cinerea on the leaves. 

PMID- 25976170
TI  - Military Veterans in the Criminal Justice System: Partner Violence and the Impact
      of Relationships With Fathers.
AB  - The objective of this study is to examine the health characteristics of military
      veterans identified through the Criminal Justice System (CJS) with partner
      violence and their relationships with their fathers. The 282 veterans involved in
      the CJS participated to complete a psycho-social assessment which included
      partner violence and ascertained their relationships with their fathers. The mean
      age of the men in the study was 44.9 years old. The majority were divorced,
      Caucasian, had a high school education, and served in the Army. This sample shows
      the benefit of integrating partner violence and relationships with fathers into
      the assessment process and highlights the need for more research. 

PMID- 25976171
TI  - Oesophageal atresia and tracheo-oesophageal fistula in Western Australia:
      Prevalence and trends.
AB  - AIM: A recent international study reported a higher prevalence of oesophageal
      atresia with or without tracheo-oesophageal fistula (OA+/-TOF) in Western
      Australia (WA). The aim of this study was to examine the prevalence and trends of
      OA and/or TOF in WA, determine the proportion of cases with associated anomalies
      and explore the impact of time of diagnosis. METHODS: The study population
      comprised all infants born in WA, 1980-2009, and registered with OA and/or TOF on
      the WA Register of Developmental Anomalies (WARDA). RESULTS: OA+/-TOF and TOF
      alone affect, on average, one in every 2927 births in WA, with a total prevalence
      of 3.00 and 0.42 per 10 000 births, respectively. The prevalence of OA+/-TOF
      increased by 2.0% per annum, with only cases with associated anomalies (64% of
      cases) demonstrating an increase. TOF rates were stable. Among OA+/-TOF infants,
      the proportion of live births, stillbirths and elective terminations of pregnancy
      for fetal anomaly (TOPFA) was 79%, 6% and 15%, respectively, whereas the majority
      (94%) of TOF only cases were live births. In 2000-2009, there was 30% fall in
      OA+/-TOF live births with 61 (58%) cases diagnosed in first week of life, 10 (9%)
      prenatally and 34 (32%) at post-mortem only. CONCLUSIONS: A higher prevalence of
      OA+/-TOF in WA was observed with increase over time attributable to increase with
      associated anomalies. Consistent reporting, availability of prenatal diagnosis
      and ascertainment of cases following TOPFA or post-mortem examinations can
      significantly affect prevalence of OA and/or TOF.

PMID- 25976172
TI  - Success of immediate loading implants compared to conventionally-loaded implants:
      a literature review.
AB  - The purpose of this systematic literature review was to compare the clinical
      performance between conventionally- (delayed) and immediately-loaded implants. A
      literature search of studies published between 1995 and 2012 was performed using
      several electronic databases and the following key words: "immediate loading",
      "dental implants", "immediate function", "early loading", "oral implants",
      "immediate restoration", and "systematic review" was performed. The electronic
      search was supplemented with hand-searching in dental journals and cross
      referencing within the selected articles. Studies were considered for inclusion
      if they analyzed the success of the immediate loading protocol for implants, with
      emphasis given to randomized, controlled clinical trials. Among the clinical
      studies extracted from the literature, 120 studies met the inclusion criteria and
      were included in this systematic review. These studies included trials that
      involved yielded consistent results of success rates of immediately-loaded
      implants comparable to those known from conventionally-loaded implants, which
      were subjected to the immediate loading protocol or other loading protocols.
      According to the findings, there is evidence to suggest that immediate loading
      protocols demonstrate high implant survival rates and could be cautiously
      recommended for certain clinical situations. However, studies with a high level
      of evidence, especially randomized, controlled trials, performed over a longer
      timeframe are required to show a clear benefit over conventional and other
      loading types. 

PMID- 25976173
TI  - Number of Nanoparticles per Cell through a Spectrophotometric Method - A key
      parameter to Assess Nanoparticle-based Cellular Assays.
AB  - Engineered nanoparticles (eNPs) for biological and biomedical applications are
      produced from functionalised nanoparticles (NPs) after undergoing multiple
      handling steps, giving rise to an inevitable loss of NPs. Herein we present a
      practical method to quantify nanoparticles (NPs) number per volume in an aqueous
      suspension using standard spectrophotometers and minute amounts of the
      suspensions (up to 1 MUL). This method allows, for the first time, to analyse
      cellular uptake by reporting NPs number added per cell, as opposed to current
      methods which are related to solid content (w/V) of NPs. In analogy to the
      parameter used in viral infective assays (multiplicity of infection), we propose
      to name this novel parameter as multiplicity of nanofection. 

PMID- 25976175
TI  - Does virus-bacteria coinfection increase the clinical severity of acute
      respiratory infection?
AB  - This retrospective cohort study investigated the presence of bacteria in
      respiratory secretions of patients hospitalized with acute respiratory infections
      and analyzed the impact of viral and bacterial coinfection on severity and the
      mortality rate. A total of 169 patients with acute respiratory infections were
      included, viruses and bacteria in respiratory samples were detected using
      molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses
      and bacteria, respectively; 45% contained both virus and bacteria. Bacterial
      coinfection was more frequent in patients infected by community respiratory
      viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria
      detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species
      were co-detected in 54 patients and identified alone in 22 and 21 patients,
      respectively. Overall, there were no significant differences in the period of
      hospitalization, severity, or mortality rate between patients infected with
      respiratory viruses alone and those coinfected by viruses and bacteria. The
      detection of mixed respiratory pathogens is frequent in hospitalized patients
      with acute respiratory infections, but its impact on the clinical outcome does
      not appear substantial. However, it should be noted that most of the patients
      received broad-spectrum antibiotic therapy, which may have contributed to this
      favorable outcome.

PMID- 25976176
TI  - Autoimmune hepatitis in adult and pediatric patients: is there any difference?

PMID- 25976174
TI  - A Novel, Highly Selective RT-QPCR Method for Quantification of MSRV Using PNA
      Clamping Syncytin-1 (ERVWE1).
AB  - HERV-W is a multi-locus family of human endogenous retroviruses (HERVs) that has
      been found to play an important role in human physiology and pathology. Two
      particular members of HERV-W family are of special interests: ERVWE1 (coding
      syncytin-1, which is a glycoprotein essential in the formation of the placenta)
      and MSRV (multiple sclerosis-associated retrovirus that is thought to play a
      significant role in human pathology as a result of its increased expression in
      the brain tissue and blood cells derived from patients with multiple sclerosis
      (MS)). Both ERVWE1 and MSRV mRNA share high level of similarity and hence a
      method that allows to exclusively quantify the MSRV expression in clinical
      samples would be desirable. We developed a quantitative polymerase chain reaction
      (QPCR) technique for the detection and quantification of the multiple sclerosis
      associated retrovirus. The assay utilises fluorescently labelled oligonucleotide
      probe, which is complementary to the conservative fragment of MSRV env gene and a
      peptide nucleic acid (PNA) probe, fully complementary to the ERVWE1 sequence
      fragment that efficiently blocks the polymerase action on ERVWE1 templates. The
      PNA molecule, if used parallel with hydrolysis probe in QPCR analysis, greatly
      facilitates the detection efficiency of MSRV even if ERVWE1 is present abundantly
      in respect to MSRV in the analysed sample. We achieved a wide and measurable
      range from 1 * 10 e(2) to 1 * 10 e(8) copies/reaction; the linearity of the
      technique was maintained even at the low MSRV level of 1% in respect to ERVWE1.
      Using our newly developed method we confirmed that the expression of MSRV takes
      place in normal human astrocytes and in human umbilical vein endothelial cells in
      vitro. We also found that the stimulation of human monocytes did not influence
      the specific expression of MSRV but it caused changes in mRNA level of distinct
      HERV-W templates.

PMID- 25976177
TI  - High rate of nickel allergy in women with endometriosis: a 3-year population
      based study.
AB  - AIM: The aim of this study was to evaluate the prevalence rates of nickel
      allergy, contact dermatitis, drug allergy, allergic rhinitis and atopic
      dermatitis among women with and without endometriosis. MATERIAL AND METHODS: Data
      were obtained from the National Patient Sample of the Republic of Korea, which
      was provided by the Korean Health Insurance Review and Assessment Service. We
      evaluated women aged 20-40 years who visited a health care institution from 2009
      2011. We estimated the prevalence of allergic diseases among women with and
      without endometriosis. RESULTS: We extracted a sample of 1 843 447 women from the
      total patient sample of approximately 3 million. We identified 7259 women with
      endometriosis and 535 818 women without endometriosis. After adjusting for age
      and data year, the women with endometriosis had higher rates of nickel allergy
      (odds ratio = 1.175; 95% confidence interval, 1.011-1.366; P = 0.04).
      Additionally, after adjusting for age, data year and other allergic diseases, the
      women with endometriosis had higher rates of nickel allergy (odds ratio = 1.167;
      95% confidence interval, 1.004-1.357; P = 0.04). After adjusting for other
      covariates, we found that other allergic disorders, such as allergic rhinitis,
      atopic dermatitis and contact dermatitis, were not associated with endometriosis.
      CONCLUSION: Women with endometriosis had higher rates of nickel allergy. Further
      research is required to clarify the relation between nickel allergy and
      endometriosis.

PMID- 25976180
TI  - Nonalcoholic Fatty Liver Disease in Latinos.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a serious public health concern that
      affects almost one third of the US population. The prevalence of NAFLD varies
      among ethnic/racial groups, with the Latin American population being affected
      disproportionately. The severity of NAFLD also may be greater in the Latino
      population. The increased prevalence and severity of NAFLD in Latino Americans
      likely is related to the interplay between issues such as genetic factors, access
      to health care, or the prevalence of chronic diseases such as metabolic syndrome
      or diabetes. In this review, we summarize the current literature on the
      prevalence and risk factors of NAFLD that are seen to be more common in the
      Latino population in the United States. Finally, we discuss available treatment
      options, medical and surgical, that are available for NAFLD and how they affect
      the Latino population. Health care providers need to address modifiable risk
      factors that impact the natural history as well as treatment outcomes for NAFLD
      among Latinos. Additional efforts are needed to improve awareness and health care
      utilization for Latinos. 

PMID- 25976178
TI  - Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch
      Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1alpha in Rats.
AB  - We have reported electroacupuncture (EA) pretreatment induced the tolerance
      against focal cerebral ischemia through activation of canonical Notch pathway.
      However, the underlying mechanisms have not been fully understood. Evidences
      suggest that up-regulation of hypoxia inducible factor-1alpha (HIF-1alpha)
      contributes to neuroprotection against ischemia which could interact with Notch
      signaling pathway in this process. Therefore, the current study is to test that
      up-regulation of HIF-1alpha associated with Notch pathway contributes to the
      neuroprotection of EA pretreatment. Sprague-Dawley rats were treated with EA at
      the acupoint "Baihui (GV 20)" 30 min per day for successive 5 days before MCAO.
      HIF-1alpha levels were measured before and after reperfusion. Then, HIF-1alpha
      antagonist 2ME2 and gamma-secretase inhibitor MW167 were used. Neurologic deficit
      scores, infarction volumes, neuronal apoptosis, and Bcl2/Bax were evaluated. HIF
      1alpha and Notch1 intracellular domain (NICD) were assessed. The results showed
      EA pretreatment enhanced the neuronal expression of HIF-1alpha, reduced infarct
      volume, improved neurological outcome, inhibited neuronal apoptosis, up-regulated
      expression of Bcl-2, and down-regulated expression of Bax after reperfusion in
      the penumbra, while the beneficial effects were attenuated by 2ME2. Furthermore,
      intraventricular injection with MW167 efficiently suppressed both up-regulation
      of NICD and HIF-1alpha after reperfusion. However, administration with 2ME2 could
      only decrease the expression of HIF-1alpha in the penumbra. In conclusion, EA
      pretreatment exerts neuroprotection against ischemic injury through Notch pathway
      mediated up-regulation of HIF-1alpha.

PMID- 25976181
TI  - A validation study of the use of near-infrared spectroscopy imaging in primary
      and secondary motor areas of the human brain.
AB  - The electroencephalographically measured Bereitschafts (readiness)-potential in
      the supplementary motor area (SMA) serves as a signature of the preparation of
      motor activity. Using a multichannel, noninvasive near-infrared spectroscopy
      (NIRS) imager, we studied the vascular correlate of the readiness potential.
      Sixteen healthy subjects performed a self-paced or externally triggered motor
      task in a single or repetitive pattern, while NIRS simultaneously recorded the
      task-related responses of deoxygenated hemoglobin (HbR) in the primary motor area
      (M1) and the SMA. Right-hand movements in the repetitive sequence trial elicited
      a significantly greater HbR response in both the SMA and the left M1 compared to
      left-hand movements. During the single sequence condition, the HbR response in
      the SMA, but not in the M1, was significantly greater for self-paced than for
      externally cued movements. Nonetheless, an unequivocal temporal delay was not
      found between the SMA and M1. Near-infrared spectroscopy is a promising,
      noninvasive bedside tool for the neuromonitoring of epileptic seizures or
      cortical spreading depolarizations (CSDs) in patients with epilepsy, stroke, or
      brain trauma because these pathological events are associated with typical
      spatial and temporal changes in HbR. Propagation is a characteristic feature of
      these events which importantly supports their identification and characterization
      in invasive recordings. Unfortunately, the present noninvasive study failed to
      show a temporal delay during self-paced movements between the SMA and M1 as a
      vascular correlate of the readiness potential. Although this result does not
      exclude, in principle, the possibility that scalp-NIRS can detect a temporal
      delay between different regions during epileptic seizures or CSDs, it strongly
      suggests that further technological development of NIRS should focus on both
      improved spatial and temporal resolution. This article is part of a Special Issue
      entitled Status Epilepticus. 

PMID- 25976179
TI  - Effects of Muscone on the Expression of P-gp, MMP-9 on Blood-Brain Barrier Model
      In Vitro.
AB  - Muscone is the main chemical ingredient in Musk which is main crude drug in
      Tongqiaohuoxue decoction (TQHXD), and TQHXD has a protective effect on damaged
      neurons, so we hypothesize that muscone can alter blood-brain barrier (BBB)
      permeability via the modulation of P-glycoprotein (P-gp) and matrix
      metalloproteinase-9 (MMP-9) expression. In this study, astrocytes (AC) and human
      umbilical vein endothelial cells (ECV304) were co-cultured to simulate the BBB
      model in vitro. Leak testing, transmembrane resistance experiments, and BBB
      specific enzyme testing were used to test whether the model was successful.
      Different concentrations of muscone permeating the BBB were detected by gas
      chromatography (GC). The change of the transendothelial electrical resistance
      (TEER) on the BBB in vitro after treating with muscone was detected by Millicell
      ERS. The protein expression of P-gp, MMP-9 in normal, and oxygen/glucose
      deprivation (OGD) BBB model was determined by western blotting to inquire that
      the mechanism of muscone penetrates the BBB model in vitro. The results show that
      muscone was detected in the lower medium of the BBB model by GC; the values of
      TEER were no significant difference before and after muscone (8 MUM) was added to
      the BBB model; the expression of P-gp significantly decreased after the BBB model
      treatment with muscone (4, 8, and 16 MUM) for 24 h; the expression of P-gp and
      MMP-9 in different concentrations of muscone groups had different degrees of
      reduction compared with the BBB in the state of OGD. In conclusion, muscone could
      permeate the BBB model, and it was associated with the inhibition of P-gp and MMP
      9 expression. An understanding of the mechanisms of muscone across the BBB is
      crucial to the development of therapeutic modalities for cerebral vascular
      diseases.

PMID- 25976182
TI  - Aberrant hippocampal neurogenesis after limbic kindling: Relationship to BDNF and
      hippocampal-dependent memory.
AB  - Seizures dramatically increase the number of adult generated neurons in the
      hippocampus. However, it is not known whether this effect depends on seizures
      that originate in specific brain regions or whether it is nonspecific to seizure
      activity regardless of origin. We used kindling of different brain sites to
      address this question. Rats received 99 kindling stimulations of the basolateral
      amygdala, dorsal hippocampus, or caudate nucleus over a 6-week period. After
      kindling, we counted the number of adult generated hippocampal neurons that were
      birth-dated with the proliferative marker bromodeoxyuridine (BrdU) to evaluate
      cell proliferation and survival under conditions of repeated seizures. Next, we
      counted the number of doublecortin immunoreactive (DCX-ir) cells and evaluated
      their dendritic complexity to determine if limbic and nonlimbic seizures have
      differential effects on neuronal maturation. We also quantified hippocampal brain
      derived neurotrophin factor (BDNF) protein levels using an ELISA kit and assessed
      memory performance using a hippocampal-dependent fear conditioning paradigm. We
      found that limbic, but not nonlimbic, seizures dramatically increased hippocampal
      cell proliferation and the number of hilar-CA3 ectopic granule cells. Further,
      limbic kindling promoted dendritic outgrowth of DCX-ir cells and the number of
      DCX-ir cells containing basal dendrites. Limbic kindling also enhanced BDNF
      protein levels throughout the entire hippocampus and impaired the retrieval of
      fear memories. Collectively, our results suggest a relationship between limbic
      seizures, neurogenesis, BDNF protein, and cognition. 

PMID- 25976183
TI  - Optical electrocorticogram (OECoG) using wide-field calcium imaging reveals the
      divergence of neuronal and glial activity during acute rodent seizures.
AB  - The role of glia in epilepsy has been widely debated. Using in vivo bulk loading
      of calcium dyes, we imaged neuronal and glial activity in an acute pharmacologic
      rodent model of neocortical seizures. Optical calcium-based ECoG maps revealed
      that neuronal waves propagated rapidly and remained mostly confined to the
      seizure focus. Glial waves were triggered by ictal onset but propagated slowly in
      a stereotypical fashion far beyond the seizure focus. Although related at their
      onset, the divergence of these two phenomena during seizure evolution calls into
      question their interdependence and the criticality of the role of glia in seizure
      onset and neurovascular coupling. This article is part of a Special Issue
      entitled "Status Epilepticus". 

PMID- 25976184
TI  - Bleeding from a gut lesion as a cause of seizure.
AB  - The differential diagnosis of causes of seizure is important since appropriate
      management depends on correct diagnosis. Making a misdiagnosis of epilepsy may
      lead to erroneous clinical management, and can be minimised with careful history
      taking and physical examination. Our educational case illustrates a patient with
      presumed epilepsy based on a witnessed generalised tonic-clonic seizure; he was
      ultimately diagnosed as upper gastrointestinal bleeding initially considered by
      careful attention of vital signs and rectal examination, and confirmed and
      treated by emergent endoscopy. Paying careful attention to the symptoms and signs
      in patients with seizure episodes is crucial to establishing a correct causative
      diagnosis for seizure. 

PMID- 25976185
TI  - No medicine is sometimes the best medicine.
AB  - A 76-year-old woman was admitted to hospital from the rheumatology outpatient
      clinic for investigation of fatigue, malaise, emotional lability, muscle
      weakness, productive cough and postural hypotension. She had been taking
      prednisone 60-40 mg daily for 6 weeks for suspected giant cell arteritis, along
      with six other regular medications, and had recently finished a course of
      antibiotics. During her admission she underwent many investigations (mostly
      negative) and treatments (largely harmful). When the diagnosis of adverse drug
      reaction was eventually reached, her medications were withdrawn and her symptoms
      gradually resolved. She was discharged home 1 month after admission, vowing never
      to return following her 'stormy course'. Adverse drug reactions are a common
      cause of avoidable hospital admissions in the elderly, estimated to cost billions
      every year. The single greatest risk factor for adverse drug reactions is the
      number of medications a person takes. Deprescribing to reduce potentially
      inappropriate medication is a possible way forward. 

PMID- 25976186
TI  - Trans-radial approach for coronary angiography in an adult postoperative patient
      with tetralogy of Fallot with complex anatomy.
AB  - A 42-year-old, postoperative patient with tetralogy of Fallot (TOF) with right
      sided aortic arch, presented with heart failure secondary to left ventricular
      dysfunction, severe valvular regurgitation and residual ventricular septal defect
      (VSD). After initial stabilisation, he underwent successful coronary angiography
      through a trans-radial approach followed by aortic valve replacement, pulmonary
      valve and VSD repair, and was discharged home in stable condition. This case
      report highlights the trans-radial approach as a feasible option for coronary
      angiography in postoperative patients with TOF with right-sided aortic arch. 

PMID- 25976187
TI  - Aceruloplasminaemia: a rare but important cause of iron overload.
AB  - We present a case of a 20-year-old man referred to our service with iron overload
      and mildly deranged liver biochemistry. Although liver histopathology was
      consistent with haemochromatosis, iron studies were not consistent with this
      diagnosis. Serum ceruloplasmin levels were undetectable, leading to a diagnosis
      of aceruloplasminaemia. Unlike other iron overload disorders, neurological
      complications are a unique feature of this illness, and often irreversible, once
      established. The patient was treated with iron chelation prior to the onset of
      neurological injury, and experienced progressive normalisation of his ferritin
      and liver biochemistry. This is one of the youngest diagnosed cases in the
      published literature and, crucially, was a rare case of diagnosis and treatment
      prior to the onset of neurological sequelae. This is presented alongside a review
      of previously published cases of aceruloplasminaemia, including responses to iron
      chelation therapy. 

PMID- 25976188
TI  - Obstructed kidney and sepsis secondary to urethral catheter misplacement into the
      distal ureter.
AB  - An 86-year-old woman underwent routine catheter replacement in the community. The
      new catheter failed to drain urine. Attempts to remove the catheter failed, both
      by the community nurse as well as by the urology team in the hospital. A CT scan
      confirmed that the catheter balloon was inflated in the distal right ureter. The
      patient was started on antibiotics and listed for cystoscopy under general
      anaesthetic. The catheter was visualised entering the right ureter and the
      balloon punctured using a wire under image intensifier guidance. Once removed, a
      new catheter was inserted. Very dilated ureteric orifices were noted. Post
      operatively the patient required HDU support for 48 h due to sepsis and on
      recovery was discharged home. The key learning point in this case is to always
      consider catheter misplacement in the ureter if it is not draining well and the
      patient presents with pain.

PMID- 25976189
TI  - Mesenterial involvement of Mycobacterium genavense infection: hard to find, hard
      to treat.
AB  - Mycobacterium genavense is a rare pathogen affecting severely immunosuppressed
      patients. We report the case of persistent relapsing M. genavense infection in a
      48-year-old African man with a positive diagnosis of HIV infection. Despite being
      under effective antiretroviral therapy with partial immune reconstitution, he
      developed irreversible long-term abdominal complications, possibly due to
      persistent M. genavense infection and sustained inflammation. Case management
      consists of individual risk assessment, close follow-up and personalised
      treatment strategies concerning the duration of antimycobacterial therapy and
      early application of steroids. Patients with profound immunosuppression, a high
      viral load at HIV diagnosis and a high burden of M. genavense, appear to be at
      higher risk. The pathogenicity of this complication is not well known and its
      optimal management has still to be determined. 

PMID- 25976190
TI  - Unexpected rare complication of the facial paralysis in a patient with an
      antrochoanal polyp following canine fossa puncture.
AB  - Canine fossa puncture (CFP) combined with endoscopic sinus surgery is a simple
      and effective method for treating antrochoanal polyps, particularly those that
      originate in the anterior, inferior or medial aspect of the antrum. Several
      complications can occur following CFP, including facial paraesthesia and dental
      numbness. However, facial palsy is extremely rare after CFP. We postulated that a
      possible mechanism of facial palsy is pressure injury to the soft tissues
      adjacent to the puncture site, which can damage the buccal branch of the facial
      nerve during CFP. 

PMID- 25976191
TI  - Sirenomelia type VI (sympus apus) in one of dizygotic twins at Chiang Mai
      University Hospital.
AB  - Those born with sirenomelia, a rare congenital anomaly, have features resembling
      a mermaid. Characteristics of sirenomelia are a single lower limb, sacral and
      pelvic bone defects, and anorectal and urogenital malformations. There is an
      increased incidence of sirenomelia in males and twins. This case was a preterm
      male, dizygotic twin and product of in vitro fertilisation. The baby was born by
      caesarean section due to breech presentation. He was found to have a fused lower
      extremity and absent external genitalia and anus. The baby passed away shortly
      after birth due to severe respiratory failure. Radiographic findings showed small
      lung volume and pneumothoraces. There were multiple segmental fusions of the
      vertebrae. Single femur and single tibia were presented in a fused lower limb.
      Autopsy demonstrated large intestinal atresia, intra-abdominal testes, absence of
      kidney, ureter and bladder, single umbilical artery, agenesis of blood vessels at
      lower extremity and agenesis of sacrum and coccyx. 

PMID- 25976192
TI  - IgA-dominant postinfectious glomerulonephritis induced by methicillin-sensitive
      Staphylococcus aureus.
AB  - A 56-year-old man with alcohol-associated cirrhosis, arterial hypertension and
      diabetes, presented with a 1-month history of fever, lumbar back pain and lower
      limb weakness. MRI revealed a spinal epidural abscess extending from the cervical
      to the dorsolumbar spine. A methicillin-sensitive Staphylococcus aureus strain
      was isolated on blood cultures. Meropenem was initially started with no response,
      and then changed to vancomycin. During treatment, the patient's condition
      progressed with anasarca and renal failure with nephrotic-range proteinuria. The
      renal biopsy showed a membranoproliferative glomerulonephritis with IgA
      deposition. After completing 2 months of antibiotic therapy the patient recovered
      from the neurological deficits, with a complete resolution of the abscess and
      partial recovery of renal function and proteinuria. 

PMID- 25976193
TI  - Laparoscopic retrieval of an intra-abdominal air gun pellet.
AB  - A 19-year-old man presented to the emergency department following an air gun
      pellet injury to the abdomen. He was clinically stable and underwent laparoscopic
      retrieval of the pellet, which was found embedded in the small bowel mesentery.
      He recovered fully and was discharged after 2 days. We further discuss air gun
      related injuries. 

PMID- 25976194
TI  - Fulminant crural compartment syndrome preceded by psychogenic polydipsia.
AB  - We report a case of bilateral anterolateral crural compartment syndrome elicited
      by hyponatraemia and psychogenic polydipsia. The unusual constellation of
      clinical findings and diminished pain expression made initial diagnostic
      procedures challenging. The possible pathogenesis and treatment options are
      discussed. Impairment of lower extremity function at follow-up was serious and
      permanent. 

PMID- 25976195
TI  - Pitfalls in the diagnostic evaluation of subacute combined degeneration.
AB  - We report a case of a 43-year-old man presenting with a 2-week history of
      painless ascending sensory disturbances, suspected to be suffering from acute
      inflammatory polyneuropathy. On clinical examination, deep tendon reflexes were
      preserved and muscle strength was 5/5 everywhere. Gait was ataxic with positive
      Romberg test. Lumbar puncture was normal and electroneurography demonstrated
      demyelination. With spinal cord involvement centred on the posterior tracts on
      MRI, differential diagnosis focused on cobalamin deficiency. Initial laboratory
      work up showed nearly normal holotranscobalamin (43 pmol/L, normal>50) suggesting
      no vitamin B12 deficiency. Surprisingly, further testing including methylmalonic
      acid (3732 nmol/L, normal<271) and homocysteine (48.5 umol/L, normal<10) showed
      an impairment of vitamin B12-dependent metabolism leading to the diagnosis of
      subacute combined degeneration. Only after repeated history taking did the
      patient remember having taken tablets containing cobalamin for 3 days before
      hospitalisation. In case of B12 deficiency, holotranscobalamin can rapidly
      normalise during supplementation, whereas methylmalonic acid and homocysteine
      might help to detect B12 deficiency in patients who recently started
      supplementation.

PMID- 25976196
TI  - Broadening the scope of thoracic oncological intervention: a novel minimally
      invasive method for the diagnosis of primary cardiac lymphoma.
AB  - Primary cardiac lymphoma is a rare and aggressive form of non-Hodgkin's lymphoma.
      It presents with non-specific symptoms which depend on the degree of cardiac
      infiltration. Appropriate management and early initiation of therapy depends on
      an understanding of the imaging characteristics and early histological diagnosis.
      Obtaining histology can be challenging. This is more widely performed using
      endomyocardial biopsy. However, this technique is associated with recognised
      morbidity and mortality. We present a novel diagnostic method for the
      investigation of myocardial and pericardial lesions. This is the first documented
      case of the diagnosis of primary cardiac lymphoma using endobronchial ultrasound.
      Endobronchial ultrasound has a well-documented and excellent safety profile. 

PMID- 25976197
TI  - Schwannoma of the sigmoid colon.
AB  - Colonic schwannomas are very rare gastrointestinal tumours originating from
      Schwann cells, which form the neural sheath. Primary schwannomas of the lower
      gastrointestinal tract are very rare and usually benign in nature. However, if
      they are not surgically removed, malign degeneration can occur. We report a case
      of a 79-year-old woman who presented to our clinic with rectal bleeding and
      constipation. She underwent a lower gastrointestinal tract endoscopy. A mass
      subtotally obstructing the lumen of the sigmoid colon was seen and biopsies were
      taken. Histopathological examination indicated a suspicion of gastrointestinal
      tumour and the patient underwent sigmoid colon resection after preoperative
      evaluation by laboratory analysis, abdominal ultrasonography and CT. Her
      postoperative course was uneventful and she was discharged on the fifth day for
      outpatient control. The histopathology report revealed schwannoma of the sigmoid
      colon. This was a case of schwannoma of the sigmoid colon that was successfully
      treated with total resection. 

PMID- 25976198
TI  - Abnormal excessive per vagina (PV) bleeding on Esmya-selective progesterone
      receptor modulator (SPRM) in a symptomatic patient with uterine fibroid.
AB  - A woman in her late 40s presented with excessive per vagina (PV) bleeding and
      uterine fibroid. She reported excessive PV bleeding after starting Esmya; she was
      brought in by ambulance to the emergency department with profuse bleeding.
      Abnormal uterine bleeding (AUB) developed after selective progesterone receptor
      modulator (SPRM) administration in this symptomatic patient with uterine fibroid.
      The drug was withheld and surgical treatment considered. Progressive
      deterioration of PV bleeding after receiving SPRM led to an urgent laparoscopic
      total hysterectomy, which had to be postponed due to severe anaemia. Surgery took
      place regardless because the excessive bleeding continued. Histology revealed a 6
      cm submucosal uterine fibroid (SMUF) and adenomyosis. Physicians prescribing
      SPRMs to stop PV bleeding should be aware of potential AUB, which could lead to
      urgent hysterectomy. The mechanism of action of SPRMs is not clearly understood.
      Awareness of the side effects of Esmya, such as AUB, must be kept in mind when
      administering SPRMs. 

PMID- 25976199
TI  - Tocilizumab for refractory organising pneumonia associated with Sjogren's
      disease.
AB  - Lung involvement in primary Sjogren syndrome occurs in approximately 10-20% of
      patients. Tocilizumab, an anti-interleukin-6 receptor antibody, has demonstrated
      efficacy and safety in small series of systemic sclerosis, and systemic lupus
      erythematosus, but its effect on interstitial lung manifestations of connective
      tissue diseases is not well known. We report the use of tocilizumab in a
      refractory organising pneumonia associated with Sjogren's disease. Our
      observation suggests that tocilizumab could be an alternative therapeutic in
      refractory organising pneumonia. 

PMID- 25976200
TI  - Glomus tumour: a rare differential for subungual lesions.
AB  - A 21-year-old, usually fit and well man, presented with a 10-year history of
      intermittent, paroxysmal pain and temperature sensitivity to his right thumb. He
      felt this was associated with a subungual lesion present on the same digit. He
      was diagnosed as having a glomus tumour and was referred to the hand surgeons for
      surgical excision. 

PMID- 25976201
TI  - Hunter syndrome with late age of presentation: clinical description of a case and
      review of the literature.
AB  - Hunter syndrome is an X linked recessive mucopolysaccharidosis (type II) caused
      by the deficiency of iduronate 2-sulfatase. This in turn leads to the
      accumulation of glycosaminoglycans, dermatan and heparan sulfate. The
      intracellular and extracellular accumulation of these substances lead to
      multisystemic organ abnormality. It is a rare syndrome with a very low prevalence
      of 1.3:100,000 male live births. Usual presentation is in early childhood
      although milder variants have been documented to present at a later age. We
      present a rare case of Hunter syndrome in a 24-year-old male patient who
      presented with joint contractures and recent onset hoarseness of voice. X-rays
      were suggestive of dysostosis multiplex. Clinical diagnosis of Hunter syndrome
      was confirmed by enzyme assay and further by mutational analysis.

PMID- 25976202
TI  - Quetiapine-induced hypertriglyceridaemia causing acute pancreatitis.
AB  - Second-generation antipsychotics have well-known metabolic side effects such as
      hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric
      and flank pain associated with nausea, and was noted to have elevated
      triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological
      parameters revealed neutropenia with pancytopaenia. The patient was started on
      conservative management for acute pancreatitis, and on intravenous insulin and
      oral gemfibrozil for lowering of his triglycerides. He gradually improved and was
      transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and
      leucocyte counts normalised at discharge and he was transitioned to ziprasidone.
      The combination of hypertriglyceridaemia, worsening hyperglycaemia and
      neutropenia made us suspect quetiapine as the causative agent. Medications cause
      only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five
      reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently
      reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or
      11.29 mmol/L) has been reported in <10 patients. 

PMID- 25976203
TI  - Occipital condyle fracture in a patient with occipitalisation of the atlas.
AB  - Occipital condyle fractures and occipitalisation of the atlas are rare entities
      of the craniocervical junction. To the best of our knowledge, a patient
      presenting with a traumatic occipital condyle fracture and pre-existing
      occipitalisation of the atlas has not been previously reported. We report the
      case of a 79-year-old man presenting with an Anderson and Montesano type III
      fracture through a fused occipital condyle and lateral mass. This fracture was
      noted to extend into the transverse foramen and the C1-C2 joint space. The
      transverse ligament and ligamentum flavum were calcified but not disrupted and
      the atlantodental interval was within normal limits. The neurological examination
      was unremarkable with the exception of neck pain. The patient was treated
      conservatively and placed in a rigid cervical collar for 10 weeks with serial CT
      studies to monitor healing of the fracture. At 4 months of follow-up, the patient
      was pain free with nearly complete resolution of his occipital condyle fracture. 

PMID- 25976204
TI  - Severe vitamin B12 deficiency in a 15-year-old boy: presentation with haemolysis
      and pancytopenia.
AB  - A 15-year-old boy on a vegetarian diet presented with severe macrocytic anaemia
      (haemoglobin, 5.1 g/dL; mean corpuscular volume, 116 fL) in addition to
      leucopenia and thrombocytopaenia (pancytopenia), icterus secondary to haemolysis
      and splenomegaly. Laboratory investigations revealed severe vitamin B12
      (cobalamin) deficiency. Following cobalamin replacement therapy, the patient
      reported increased well-being, including appetite and weight gain, and his
      icterus resolved. In the follow-up laboratory examinations, leucocyte and
      platelet counts in addition to serum bilirubin and lactate dehydrogenase levels
      normalised. At the end of 2 months, laboratory findings, including haemoglobin
      level, were all within the normal range. We present this case as a reminder that
      severe vitamin B12 deficiency may present with findings mimicking acute leukaemia
      (pancytopenia and splenomegaly) and findings suggestive of pseudothrombotic
      microangiopathy. 

PMID- 25976205
TI  - Luftsichel sign and juxtaphrenic peak sign.

PMID- 25976206
TI  - Uncommon variants of left circumflex coronary artery (LCX): evaluation with 256
      slice dual source CT coronary angiography.

PMID- 25976207
TI  - M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1alpha
      in human breast cancer cells.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a primary transcriptional factor that
      targets a series of genes participating in angiogenesis and cell proliferation.
      HIF-1 is a heterodimer consisting of a constitutively-expressed HIF-1beta subunit
      and an oxygen-regulated HIF-1alpha subunit. Overexpression of HIF-1alpha has been
      found in various types of cancer. Targeting HIF-1alpha may be a novel approach to
      cancer therapy. Previous findings showed that a newly synthesized compound (Z)
      3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410), an analogue of the
      microtubule-targeting agent, combretastatin A4, inhibited the polymerization of
      bovine brain tubulin and induced mitotic arrest. The aim of the present study was
      to determine the mechanism of M410 destabilizes microtubules and inhibits HIF
      1alpha in breast cancer cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, immunofluorescence and confocal
      microscopy, ELISA assay, transient transfections and reporter gene assay,
      immunoblot analysis and isolation and analysis of RNA to evaluate the mechanisms
      of M410 on breast cancer. SPSS 17.0 was used to analyze the data. The results
      showed that the growth of breast cancer cells was inhibited in a dose-dependent
      manner. MDA-MB-231 was the most sensitive, with a 50% growth inhibition (GI50) of
      111.4+/-2.2 nM. HIF-1alpha expression was clearly reduced following M410
      treatment in a dose-dependent manner. M410 downregulated the nuclear accumulation
      of HIF-1alpha, and the strong correlation between disruption of the microtubule
      cytoskeleton and the inhibition of HIF-1alpha expression was independent of
      mitotic arrest. Furthermore, M410 inhibited HIF-1alpha at the post
      transcriptional level and inhibited the vascular endothelial growth factor (VEGF)
      at the transcription level. M410 downregulated HIF-1alpha expression in a
      proteasome-independent manner. In conclusion, M410 depolymerized microtubules and
      downregulated HIF-1alpha protein levels in a proteasome-independent manner and
      reduced the mRNA of HIF-1-targeted genes in the MDA-MB-231 breast cancer cell
      line.

PMID- 25976208
TI  - An unsupervised feature learning framework for basal cell carcinoma image
      analysis.
AB  - OBJECTIVE: The paper addresses the problem of automatic detection of basal cell
      carcinoma (BCC) in histopathology images. In particular, it proposes a framework
      to both, learn the image representation in an unsupervised way and visualize
      discriminative features supported by the learned model. MATERIALS AND METHODS:
      This paper presents an integrated unsupervised feature learning (UFL) framework
      for histopathology image analysis that comprises three main stages: (1) local
      (patch) representation learning using different strategies (sparse autoencoders,
      reconstruct independent component analysis and topographic independent component
      analysis (TICA), (2) global (image) representation learning using a bag-of
      features representation or a convolutional neural network, and (3) a visual
      interpretation layer to highlight the most discriminant regions detected by the
      model. The integrated unsupervised feature learning framework was exhaustively
      evaluated in a histopathology image dataset for BCC diagnosis. RESULTS: The
      experimental evaluation produced a classification performance of 98.1%, in terms
      of the area under receiver-operating-characteristic curve, for the proposed
      framework outperforming by 7% the state-of-the-art discrete cosine transform
      patch-based representation. CONCLUSIONS: The proposed UFL-representation-based
      approach outperforms state-of-the-art methods for BCC detection. Thanks to its
      visual interpretation layer, the method is able to highlight discriminative
      tissue regions providing a better diagnosis support. Among the different UFL
      strategies tested, TICA-learned features exhibited the best performance thanks to
      its ability to capture low-level invariances, which are inherent to the nature of
      the problem.

PMID- 25976209
TI  - Corrigendum: Host genetic determinants of microbiota-dependent nutrition revealed
      by genome-wide analysis of Drosophila melanogaster.

PMID- 25976210
TI  - Invariant natural killer T cells and their ligands: focus on multiple sclerosis.
AB  - Invariant natural killer T (iNKT) cells are an innate population of T cells
      identified by the expression of an invariant T-cell receptor and reactivity to
      lipid-based antigens complexed with CD1d. They account for a small percentage of
      lymphocytes, but are extremely potent and play central roles in immunity to
      infection, in some cancers, and in autoimmunity. The list of relevant stimulatory
      lipids and glycolipid antigens now includes a range of endogenous self-antigens
      including the myelin-derived acetylated galactosylceramides. Recent progress in
      studies to identify the nature of lipid recognition for iNKT cells in autoimmune
      diseases like multiple sclerosis is likely to foster the development of
      therapeutic strategies aimed at harnessing iNKT cell activity. 

PMID- 25976211
TI  - Targeting drug sensitivity predictors: New potential strategies to improve
      pharmacotherapy of human brain disorders.
AB  - One of the main challenges in medicine is the lack of efficient drug therapies
      for common human disorders. For example, although depressed patients receive
      powerful antidepressants, many often remain resistant to psychopharmacotherapy.
      The growing recognition of complex interplay between the drug targets and the
      predictors of drug sensitivity requires an improved understanding of these two
      key aspects of drug action and their potentially shared molecular networks. Here,
      we apply the concept of endophenotypes and their interplay to drug action and
      sensitivity. Based on these analyses, we postulate that novel drugs may be
      developed by targeting specific molecular pathways that integrate drug targets
      with drug sensitivity predictors. 

PMID- 25976212
TI  - Influences of increased training volume on exercise performance, physiological
      and psychological parameters.
AB  - BACKGROUND: The aim of this study was to investigate the influence of excessive
      training on exercise performance and physiological and psychological parameters.
      METHODS: Eight physically active males (age, mean+/-standard deviation [SD]: 23+/
      3 years) completed 3 weeks of an intervention program consisting of normal (N),
      intensified (IT), and recovery (R) training phases (7 days for each phase).
      Physiological and psychological parameters were measured at rest before the
      intervention (Pre), and every Monday, Wednesday, and Saturday (day 1, day 3, day
      6, respectively), and exercise performance tests were performed before the
      intervention (Pre) and every Saturday (day 6) during the intervention period.
      RESULTS: The estimated energy expenditure during a training session revealed a
      more than two-fold increase from the N phase to the IT phase. During the IT
      phase, augmented training volume significantly affected the POMS (fatigue) and
      motivation towards training (P<0.05) scores, and these values returned to
      baseline levels during the R phase. Moreover, resting serum testosterone
      concentrations significantly decreased and exercise-induced cortisol responses
      were diminished during the IT phase (P<0.05). The altered endocrine responses
      were still observed during the subsequent R phase. Resting serum BAP levels (an
      index of antioxidant potential) significantly increased during the N phase
      (P<0.05). Meanwhile, there was no significant change in exercise performance,
      resting d-ROM (an index of oxidative stress) values, or salivary amylase
      activity. CONCLUSIONS: Increases in training stress altered psychological
      parameters, resting testosterone concentrations, and exercise-induced cortisol
      responses. Exercise performance did not correlate with training stress,
      suggesting that monitoring endocrine and psychological parameters is essential
      during intensified training periods.

PMID- 25976214
TI  - From first symptoms to final diagnosis of Cushing's disease: experiences of 176
      patients.

PMID- 25976213
TI  - Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell
      therapy? Where are we headed in cartilage repair and why: a concise review.
AB  - The evolution of articular cartilage repair procedures has resulted in a variety
      of cell-based therapies that use both autologous and allogeneic mesenchymal
      stromal cells (MSCs). As these cells are increasingly available and show
      promising results both in vitro and in vivo, cell-based strategies, which aim to
      improve ease of use and cost-effectiveness, are progressively explored. The use
      of MSCs in cartilage repair makes it possible to develop single-stage cell-based
      therapies. However, true single-stage procedures rely on one intervention, which
      will limit cell sources to fraction concentrates containing autologous MSCs or
      culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic
      cells can safely be applied, but clinical studies are still ongoing and little
      information on clinical outcome is available. Further development of cell-based
      therapies may lead to clinical-grade, standardized, off-the-shelf products with
      easy handling for orthopedic surgeons. Although as of yet no preclinical or
      clinical studies are ongoing which explore the use of induced pluripotent stem
      cells for cartilage repair, a good manufacturing practice-grade induced
      pluripotent stem cell line might become the basis for such a product in the
      future, providing that cell fate can be controlled. The use of stem cells in
      clinical trials brings along new ethical issues, such as proper controls and
      selecting primary outcome measures. More clinical trials are needed to estimate
      detailed risk-benefit ratios and trials must be carefully designed to minimize
      risks and burdens for patients while choosing outcome measures that allow for
      adequate comparison with results from similar trials. In this review, we discuss
      the different aspects of new stem cell-based treatments, including safety and
      ethical issues, as well as provide an overview of current clinical trials
      exploring these approaches and future perspectives. 

PMID- 25976215
TI  - New York City Taxi Drivers' Knowledge and Perceptions of the Affordable Care Act.
AB  - This study was conducted to assess New York City taxi drivers' knowledge and
      perceptions of the Affordable Care Act (ACA). A cross-sectional street-intercept
      study design was used to assess drivers' knowledge about the ACA. A 146-item
      questionnaire was administered from September 12 to December 6, 2013 to 175
      yellow taxi and for-hire vehicle drivers. 91 % of drivers were foreign-born; 50 %
      were uninsured. Mean knowledge about the ACA was quite low; 78 % of the sample
      either knew nothing or only a little bit about the ACA. 77 % wanted more
      information about the ACA. Greater English proficiency, more years driving a
      taxi, and knowledge of having or not having a pre-existing health condition (vs.
      not knowing) were related to higher ACA knowledge levels. Knowledge of a pre
      existing condition (whether they had one or not) compared to those who lacked
      such knowledge was also an important predictor of the perception of whether the
      ACA would have a positive impact. To facilitate enrollment, efforts should focus
      on occupationally-focused initiatives that educate drivers at their places of
      work and leisure, to raise the overall knowledge levels and enrollment of the
      community.

PMID- 25976216
TI  - Comparison of saliva interleukin-2 concentration to the condition of gums in
      children with acute lymphoblastic leukaemia during anti-tumour treatment.
AB  - PURPOSE: Subjects undergoing chemotherapy often develop disorders in salivation
      and changes in salivary composition. Therefore, a tendency to inflammatory states
      developing within oral mucosa is often observed. The objective of the study was
      to assess the effect of disturbed immunity on the gum condition in children with
      acute lymphoblastic leukaemia (ALL) during anti-tumour treatment and to compare
      saliva interleukin-2 (IL-2) concentration in relation to the condition of gums
      oral mucositis-must be removed in children with ALL. METHODS: The study included
      78 children with ALL in followed three examinations and a control group included
      78 healthy children. Dental examination of the children with ALL and the control
      group included the evaluation of gingival condition by gingival index (GI).
      Children's unstimulated saliva samples were taken, and IL-2 concentration was
      determined by Human IL-2 EIA. RESULTS: Mean GI higher than 1 was observed in 3.17
      % children with ALL. The results found higher frequency of gingival inflammations
      in children with ALL on chemotherapy compared with the healthy controls. A
      comparison of results for a given patient during anti-tumour therapy with regard
      to salivary IL-2 showed significant differences between examination 2 and
      examination 3. The results indicated that IL-2 level in saliva was twice higher
      in a patient during chemotherapy. CONCLUSIONS: An increase in salivary level of
      the proinflammatory IL-2 cytokine in ALL children during chemotherapy may cause
      pathological changes in the condition of the gums. An increase in salivary IL-2
      level most probably results from a micro-injury of oral mucosa following
      administration of cytostatics, which in turn may cause oral mucositis in children
      with ALL.

PMID- 25976217
TI  - Second-line docetaxel for patients with platinum-refractory advanced non-small
      cell lung cancer and interstitial pneumonia.
AB  - PURPOSE: The role of second-line chemotherapy in patients with non-small cell
      lung cancer (NSCLC) and preexisting interstitial pneumonia (IP) previously
      treated with platinum-based chemotherapy remains uncertain. This study was
      conducted to elucidate the efficacy and tolerability of second-line docetaxel
      monotherapy for patients with platinum-refractory advanced (stage IIIB, IV, or
      relapse) NSCLC and preexisting IP. METHODS: A total of 35 patients (median age,
      67 years) treated with docetaxel monotherapy in a second-line setting following
      first-line platinum-based chemotherapy between January 2002 and December 2013
      were retrospectively reviewed. RESULTS: The overall response rate and disease
      control rate were 8.6 % [95 % confidence interval (CI) 0-17.9 %] and 37.1 % (95 %
      CI 21.1-53.1 %), respectively. The median progression-free survival and median
      overall survival periods were 1.6 months (95 % CI 1.2-2.0 months) and 5.1 months
      (95 % CI 3.2-6.7 months), respectively. The incidence of acute exacerbation (AE)
      of IP following docetaxel monotherapy was 14.3 % (5/35 patients). Of the five
      patients who developed AE of IP, three patients died. The toxicity of this
      regimen was substantial, with treatment-related deaths occurring in 5 (14.3 %)
      patients (AE of IP: 3, sepsis: 2). CONCLUSIONS: Docetaxel monotherapy has a poor
      activity and substantial risks when used for the treatment of platinum-resistant
      NSCLC with IP. Novel therapeutic approaches should be explored in this setting.

PMID- 25976218
TI  - Low-dose Methylphenidate Monotherapy for Features of Attention
      Deficit/Hyperactivity Disorder Secondary to Hereditary Cerebellar Ataxia.

PMID- 25976219
TI  - Effects of continuous midwifery labour support for women with severe fear of
      childbirth.
AB  - BACKGROUND: Continuous support by a midwife during childbirth has shown positive
      effects on the duration of active labour, use of pain relief and frequency of
      caesarean section (CS) in women without fear of childbirth (FOC). We have
      evaluated how continuous support by a specially assigned midwife during
      childbirth affects birth outcome and the subjective experience of women with
      severe FOC. METHODS: A case-control pilot study with an index group of 14 women
      with severe FOC and a reference group of 28 women without FOC giving birth. In
      this study the index group received continuous support during childbirth.
      RESULTS: The women with severe FOC more often had an induction of labour. The
      parous women with severe FOC had a shorter duration of active labour compared to
      the parous reference women (p = 0.047). There was no difference in caesarean
      section frequency between the two groups. Women with severe FOC experienced a
      very high anxiety level during childbirth (OR = 20.000, 95% CI: 3.036-131.731).
      CONCLUSION: Women with severe FOC might benefit from continuous support by a
      midwife during childbirth. Midwives should acknowledge the importance of
      continuous support in order to enhance the experience of childbirth in women with
      severe FOC.

PMID- 25976220
TI  - Impact of the environmental conditions and substrate pre-treatment on whey
      protein hydrolysis: A review.
AB  - Proteins in solution are subject to myriad forces stemming from interactions with
      each other as well as with the solvent media. The role of the environmental
      conditions, namely pH, temperature, ionic strength remains under-estimated yet it
      impacts protein conformations and consequently its interaction with, and
      susceptibility to, the enzyme. Enzymes, being proteins are also amenable to the
      environmental conditions because they are either activated or denatured depending
      on the choice of the conditions. Furthermore, enzyme specificity is restricted to
      a narrow regime of optimal conditions while opportunities outside the optimum
      conditions remain untapped. In addition, the composition of protein substrate
      (whether mixed or single purified) have been underestimated in previous studies.
      In addition, protein pre-treatment methods like heat denaturation prior to
      hydrolysis is a complex phenomenon whose progression is influenced by the
      environmental conditions including the presence or absence of sugars like
      lactose, ionic strength, purity of the protein, and the molecular structure of
      the mixed proteins particularly presence of free thiol groups. In this review, we
      revisit protein hydrolysis with a focus on the impact of the hydrolysis
      environment and show that preference of peptide bonds and/or one protein over
      another during hydrolysis is driven by the environmental conditions. Likewise,
      heat-denaturing is a process which is dependent on not only the environment but
      the presence or absence of other proteins.

PMID- 25976221
TI  - Protective effect of 2-deoxy-D-glucose on the cytotoxicity of cyclosporin A in
      vitro.
AB  - The present study aimed to investigate the mechanism underlying the protective
      effect of 2-deoxy-D-glucose (2-DG) on the cytotoxicity of cyclosporin A (CsA) in
      vitro using NRK-52E cells. Staining with Hoechst 33342/propidium iodide prior to
      flow cytometric analysis was performed to assess the rate of cellular apoptosis
      and necrosis induced by CsA. The expression levels of lactate dehydrogenase
      (LDH), caspase 3, receptor-interacting protein kinase 3 (RIP3), reactive oxygen
      species (ROS), glutathione (GSH) and malondialdehyde (MDA) were detected using
      colorimetry, ELISA, western blotting or flow cytometric analysis to determine the
      protective effects of 2-DG on CsA-induced cell death. The results demonstrated
      that 2-DG inhibited the release of LDH, the activation of caspase 3 and the
      generation of ROS induced by CsA, but had no effect on the expression of RIP3.
      Treatment with 2-DG increased the expression of GSH and decreased the expression
      of MDA in dose-dependent manner, and reduced the rate of the cellular apoptosis
      and necrosis induced by CsA. Therefore, 2-DG inhibited CsA-induced cellular
      apoptosis and necrosis, possibly by reducing the production of ROS. Inhibiting
      the activation of caspase 3 is one of the protective mechanisms of 2-DG, however,
      the expression of RIP3 remained unaltered following treatment with 2-DG. Whether
      2-DG inhibits the CsA-induced necrosis and apoptosis by inhibiting the RIP3
      signaling pathway remains to be elucidated.

PMID- 25976222
TI  - Modeling the heterogeneous intestinal absorption of propiverine extended-release.
AB  - Propiverine is a widely used antimuscarinic drug with bioavailability that is
      limited by intestinal first-pass extraction. To study the apparent heterogeneity
      in intestinal first-pass extraction, we performed a population analysis of oral
      concentration-time data measured after administration of an extended-release
      formulation of propiverine in ten healthy subjects. Using an inverse Gaussian
      function as input model, the assumption that the systemically available fraction
      increases as a sigmoidal function of time considerably improved the fit. The step
      like increase in this fraction at time t=3.7h predicted by the model suggests
      that propiverine is predominantly absorbed in colon. A nearly perfect correlation
      was found between the estimates of bioavailability and mean dissolution time. 

PMID- 25976223
TI  - CYP3A4*18B and CYP3A5*3 polymorphisms contribute to pharmacokinetic variability
      of cyclosporine among healthy Chinese subjects.
AB  - AIM: Cyclosporine is an immunosuppressant drug used to prevent allograft
      rejection. It is metabolized by CYP3A4 and CYP3A5, has a narrow therapeutic
      index, and variable pharmacokinetics. Here, we investigated whether CYP3A5*3 and
      CYP3A4*18B polymorphisms contribute to inter-individual pharmacokinetic
      variability in healthy subjects. PATIENTS AND METHODS: Fifty-six healthy Chinese
      subjects were enrolled in the study after signing a written consent. The subjects
      received 5mgkg(-1) of cyclosporine orally and were genotyped for CYP3A5*3 and
      CYP3A4*18B using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Blood concentrations of cyclosporine were measured by
      high-performance liquid chromatography for up to 30h post-dose. RESULTS: The mean
      cyclosporine AUC0->30 and AUC0->infinity in the male group was significantly
      higher than that in the female group (P=0.037 and 0.035); the CL/F in the male
      group was significantly lower than that in the female group (P=0.033). The Cmax
      of cyclosporine in CYP3A4*1/*1 was significantly greater than that in
      CYP3A4*1/*18B in the male group (P=0.023), but not the female group. In addition,
      the Cmax in CYP3A5*1/*3 was significantly lower than that in CYP3A5*3/*3 in the
      male group (P=0.01). CONCLUSIONS: The results indicate that gender and
      polymorphism in CYP3A4*18B and CYP3A5*3 significantly affect cyclosporine
      pharmacokinetics in healthy subjects.

PMID- 25976224
TI  - The enhancement of cardiac toxicity by concomitant administration of Berberine
      and macrolides.
AB  - As is well-known, hERG plays an essential role in phase III repolarization of
      cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition
      of the metabolism of CYPs activities may elevate plasma levels, to further
      increase accumulation of drug on cardiac. The elevated serum levels may however
      elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are
      central to the preclinical studies because they may lead to severe cardiac
      toxicity. Berberine is widely used as an antibacterial agent and often combined
      with macrolides to treat gastropathy. Our objective was to assess cardiac
      toxicity during the combined use of Berberine with macrolides. (1) Azithromycin
      reduced hERG currents by accelerated channel inactivation. (2) The combination of
      Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect
      stronger than use of a single drug alone, due to the high binding affinity for
      the onset of inactivation. (3) When cells were perfused concomitantly with
      Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG
      currents by decreasing the time constant for the onset of inactivation. (4) The
      combined administration of Berberine with Clarithromycin had a powerful
      inhibitive effect on CYP3A activities than use of a single drug alone.
      Collectively, these results demonstrated that concomitant use of Berberine with
      macrolides may require close monitoring because of potential drug toxicities,
      especially cardiac toxicity. 

PMID- 25976225
TI  - Tanshinone IIA - loaded pellets developed for angina chronotherapy: Deconvolution
      based formulation design and optimization, pharmacokinetic and pharmacodynamic
      evaluation.
AB  - This paper put forward a deconvolution-based method for designing and optimizing
      tanshinone IIA sustained-release pellets (TA-SRPs) with improved efficacy in the
      treatment of variant angina. TA-SRPs were prepared by coating TA ternary solid
      dispersion immediate-release pellets (TA-tSD-IRPs) with the blends of polyvinyl
      acetate (PVAc) and polyvinyl alcohol-polyethylene glycol (PVA-PEG) using
      fluidized bed technology. The plasma concentration-time curve of TA-tSD-IRPs
      following oral administration as a weight function was investigated in New
      Zealand white rabbits. The predicted/expected plasma concentration-time curve of
      TA-SRPs as a response function was simulated according to the circadian rhythm of
      variant angina during 24h based on chronotherapy theory. The desired drug release
      profile of TA-SRPs was obtained via the point-area deconvolution procedure using
      the weight function and response function, and used for formulation optimization
      of TA-SRPs. The coating formulation of TA-SRPs was optimized as 70:30 (w/w)
      PVAc/PVA-PEG with 5% (w/w) coating weight due to in vitro drug release profile of
      these TA-SRPs was similar to the desired release profile (similarity factor
      f2=64.90). Pharmacokinetic studies of these optimized TA-SRPs validated that
      their actual plasma concentration-time curve possessed a basically consistent
      trend with the predicted plasma concentration-time curve and the absolute percent
      errors (%PE) of concentrations in 8-12h were less than 10%. Pharmacodynamic
      studies further demonstrated that these TA-SRPs had stable and improved efficacy
      with almost simultaneous drug concentration-efficacy. In conclusion,
      deconvolution could be employed in the development of TA-SRPs for angina
      chronotherapy with simultaneous drug efficacy and reduced design blindness and
      complexity. 

PMID- 25976226
TI  - Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation.
AB  - Overcoming multidrug resistance (MDR) in cancer is a major challenge and efforts
      are on-going to develop inhibitors against the most characterized and ubiquitous
      MDR transporters: P-glycoprotein (P-gp), multidrug resistance-associated protein
      (MRP1) and breast cancer resistance protein (BCRP). Recently reported, two 4
      anilinoquinazolines (compounds 1 and 2), demonstrate potential MDR reversal
      activity against BCRP and to a lesser extent, P-gp. In this work, we formulated
      the compounds as polymeric nanoparticles (NPs) and assessed their MDR inhibitory
      activity in relevant BCRP and P-gp over-expressing cell line models. Particles in
      the size range 300-365nm with a loading efficiency of 69% (compound 1 NP) and 77%
      (compound 2 NP) respectively were obtained. BCRP inhibition was observed in
      Hoechst 33342 and pheophorbide A assays while P-gp inhibition was evaluated in
      calcein AM and rhodamine-123 assays. In cytotoxicity studies, while BCRP
      expressing cells showed complete reversal of drug resistance in nearly all
      treatment groups (both compounds and their respective NP); a higher reversal in
      NP treated group was obtained as compared with inhibitory compound treated group
      in P-gp expressing cells. These results demonstrate promising inhibitory activity
      of both formulations, especially against P-gp expressing cells; which is possibly
      due to a prolonged presence of encapsulated compounds in NPs and consequently a
      prolonged sensitization of transmembrane drug transporter. These formulations can
      therefore be considered as dual-transporter inhibitors and it is imperative to
      investigate both inhibitors in animal models of MDR owing to the presence of
      multiple efflux transporters in several cancer models.

PMID- 25976227
TI  - Exploration of the content validity and feasibility of the EQ-5D-3L, ICECAP-O and
      ASCOT in older adults.
AB  - BACKGROUND: In economic evaluations of care services for older adults health
      related quality of life (QoL) measures such as the EQ-5D are increasingly
      replaced by the ICECAP-O and ASCOT, which cover a broader scope of QoL than
      health alone. Little is known about the content validity and feasibility of these
      measures. The purpose of this study was to explore the content validity and
      feasibility of the EQ-5D-3L, ICECAP-O and ASCOT in older adults. METHODS: Ten
      older adults were purposively sampled using a maximum variation principle. Think
      aloud and verbal probing techniques were used to identify response issues
      encountered during the interpretation of items and the selection of response
      options. We used constant comparative methods to analyse the data. RESULTS: Two
      types of response issues were identified for various items in all three measures:
      interpretation issues and positive responses. Issues with the mapping of a
      response on one of the response options were least often encountered for the EQ
      5D-3L items. Older adults considered the items of the ICECAP-O and ASCOT valuable
      though more abstract than the EQ-5D-3L. CONCLUSIONS: Researchers who intend to
      use the EQ-5D, ICECAP-O or ASCOT in economic evaluations of care services for
      older adults, should be aware of the response issues that occur during the
      administration of these measures. Older adults perceived none of the measures as
      providing a comprehensive picture of their QoL. A preference from older adults
      for one of the measures depends on the extent to which the items reflect current
      personal concerns in life.

PMID- 25976228
TI  - Prognostic value of troponins in acute nonmassive pulmonary embolism: A meta
      analysis.
AB  - The objective of our meta-analysis is to update the evidence on the prognostic
      value of elevated troponin levels in patient with acute normotensive pulmonary
      embolism (PE). We did a systematic literature review of database, including
      Pubmed, EMBASE, and Cochrane. Studies were included if those were done on
      normotensive patients with acute PE and serum troponin assay was done. The
      primary end point was short term all cause mortality. The secondary end points
      were short term PE related mortality and serious adverse events. Elevated
      troponin levels were significantly associated with the increased risk for short
      term mortality (odds ratio [OR], 4.80; 95% CI, 3.25-7.08, I(2) = 54%), PE related
      mortality (OR, 3.80; 95% CI, 2.74-5.27, I(2) = 0%) and serious adverse events
      (OR, 3.65; 95% CI, 2.41-5.53, I(2) = 47%). Our study suggests that elevated
      levels of troponin identify a subgroup of patients with increased risk for short
      term mortality and serious adverse events. 

PMID- 25976229
TI  - Subcellular G-protein coupled receptor signaling hints at greater therapeutic
      selectivity.
AB  - G-protein coupled receptors (GPCRs) evolved as specialized sensors of the
      extracellular environment. Comprising the largest family of cell surface
      receptors, GPCRs are common therapeutic targets. Over the last 25 years, several
      GPCRs have been observed at the cell nucleus, suggesting the presence of
      intracrine GPCR signaling beyond the plasma membrane. Yet specific physiological
      functions of nuclear GPCRs had not been reported, until lately. We recently
      uncovered distinct but complementary angiogenic roles of F2rl1 (formerly known as
      PAR2) depending on its subcellular localization at the plasma membrane or at the
      nucleus. Targeting subcellular compartments to improve drug selectivity may
      therefore inspire novel therapeutic strategies for transmembrane receptors. 

PMID- 25976230
TI  - Neutralizations of IL-17A and IL-21 regulate regulatory T cell/T-helper 17
      imbalance via T-helper 17-associated signaling pathway in immune
      thrombocytopenia.
AB  - OBJECTIVE: The imbalance of regulatory T cell/T-helper 17 (Treg/Th17) is critical
      for the pathogenesis of immune thrombocytopenia (ITP) and IL-17A and IL-21 are
      overexpressed in ITP. The effects and mechanisms of IL-17A and IL-21 in Treg/Th17
      imbalance and ITP pathophysiology are not clarified. METHODS: Peripheral blood
      mononuclear cells (PBMCs) and CD3(+) T cells from ITP patients and healthy
      controls were treated with cytokines or antibodies to increase or neutralize IL
      17A or IL-21 levels for 72 h. Treg/Th17 differentiation, apoptosis, proliferation
      and Th17 differentiation-associated transcriptional factors were analyzed.
      RESULTS: Natural Treg/Th17 decreased in newly diagnosed ITP patients and
      recovered after remission. IL-17A or IL-21 increased Th17, decreased Tregs and
      downregulated Treg/Th17 in vitro. Conversely, neutralization of IL-17A or IL-21
      decreased Th17, increased Tregs and up-regulated Treg/Th17. The reverse effects
      of IL-17A or IL-21 were mediated by Th17-associated transcriptional factors. IL
      17A or IL-21 enhanced STAT-1, STAT-3, STAT-5 or RAR-related orphan receptor C
      (RORC), whereas anti-IL-17A or anti-IL-21 mAb downregulated STAT-1, STAT-5 or
      RORC transcripts in ITP PBMCs. Proliferation showed no significant difference. IL
      21 inhibited apoptosis in ITP PBMCs. CONCLUSION: IL-17A and IL-21 induce Th17 and
      inhibit Tregs re-differentiation via Th17-associated signaling pathway in ITP
      patients in vitro. It highlights the potential value of IL-17A or IL-21 blockade
      as a novel therapeutic target for ITP.

PMID- 25976231
TI  - Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a
      candidate for cutaneous melanoma therapy.
AB  - OBJECTIVE: We aimed to verify if there is evidence to consider dichloroacetate
      (DCA), which inhibits the pyruvate dehydrogenase kinase (PDK) and reverts the
      metabolic shift of cancer cells from glycolysis to oxidative phosphorylation, as
      a promising drug for therapy of cutaneous melanoma (CM) patients. RESEARCH DESIGN
      AND METHODS: We assessed the expression profile of PDK 1, 2 and 3 in a series of
      melanoma samples, to verify if melanoma tumors express the DCA targets, if this
      expression correlates with the activation of important signaling cascades for
      melanomagenesis and also with the prognosis of melanoma patients. We also
      established the sensitivity of melanoma cell lines to DCA treatment, by assessing
      their metabolic alterations, proliferation and survival. RESULTS: We observed
      that both PDK 1 and 2 isoforms are overexpressed in CM compared to nevi, this
      expression being associated with the expression of the mTOR pathway effectors and
      independent of the BRAF mutational status. Melanoma cell lines treated with DCA
      showed a shift in metabolism, that is, a decrease in glucose consumption and
      lactate production, downregulation of proliferation, an increase of apoptosis and
      a decrease in mTOR pathway activation. CONCLUSION: Our results suggest that PDK
      expression may play a role in melanoma development and that DCA can be useful for
      CM therapy, alone or in combination with mTOR inhibitors.

PMID- 25976233
TI  - Body image perceptions among women with pre-existing physical disability who
      developed breast cancer: a qualitative exploration.

PMID- 25976234
TI  - The complete mitochondrial genome sequence of Schizothorax lissolabiatus
      (Cypriniformes: Cyprinidae).
AB  - Schizothorax lissolabiatus is a widely distributed fish species in Lancang River,
      Yuanjiang River, Pearl River, Nujiang River in China. The complete mitochondrial
      genome sequence of S. lissolabiatus from Yuanjiang River (the upper Red River)
      has been sequenced, which is 16,583 bp in length and contains 22 tRNA genes, 13
      protein-coding genes, 2 rRNA genes and 2 main non-coding regions: origin of light
      strand replication and control region. Except for eight tRNA and ND6 genes, most
      of the genes are encoded on the heavy strand. The length of mitochondrial genome,
      the order, composition and anticodons of all genes are exactly similar to that of
      S. dolichonema. The phylogenetic tree suggested S. prenanti, S. dolichonema and
      S. lissolabiatus may have closer affinities than other fish of the genus
      Schizothorax.

PMID- 25976235
TI  - Ticks and tick-borne pathogens in South Bohemia (Czech Republic)--Spatial
      variability in Ixodes ricinus abundance, Borrelia burgdorferi and tick-borne
      encephalitis virus prevalence.
AB  - Spatial distribution of Ixodes ricinus tick host-seeking activity, as well as
      prevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus
      (TBEV) were studied in the TBE endemic area of South Bohemia (Czech Republic).
      High variability in tick abundance detected in a network of 30 study sites was
      most closely associated with characteristics of vegetation cover. Of 11,182
      tested tick samples, 12% carried DNA of spirochete from B. burgdorferi s.l.
      complex. B. afzelii and B. garinii prevailed among spirochete species. The
      presence of B. spielmanii in the region was confirmed. The median number of
      borrelial genome copies in positive samples reached 6.6 * 10(3) by real-time PCR.
      The total prevalence of TBEV in pooled samples reached 0.32% (20,057 samples
      tested), at least one TBEV positive tick was present in 21 out of 30 sampling
      sites.

PMID- 25976236
TI  - TripAdvisor for fertility clinics.

PMID- 25976237
TI  - Immunolocalization of Aquaporins 1 and 9 in the Ram Efferent Ducts and
      Epididymis.
AB  - Aquaporins (AQPs) are essential membrane protein channels for the transport of
      water across membranes. Fluid movement in the epididymis is important for
      modulation of the luminal environment, in which sperm mature and reside. This
      study was designed to understand the morphology and localization of AQPs in ram
      efferent ducts (ED) and epididymis. For this purpose, the epididymis of seven
      animals were removed for histologic and immunohistochemical analyses. AQP1
      immunoreactivity was observed in the apex of the ED, and AQP9 was found adjacent
      to the nuclei of the epithelial cells of the ED. The epithelial lining of ram
      epididymis is pseudostratified columnar and presents principal, basal, apical and
      narrow cells. In the initial segment (IS), a moderate reaction for AQP1 was
      observed in the apical cytoplasm of epithelial cells. An intense reactivity for
      AQP1 was noted over the microvilli of principal cells and in spermatozoa in the
      caput. In the corpus and cauda, AQP1 was noted only over the endothelial cells of
      vascular channels located in intertubular spaces. A weak-to-moderate reaction for
      AQP9 was observed in the nuclei of epithelial cells in the IS, caput and corpus
      of the epididymis. In the cauda, an intense reaction to AQP9 was observed in the
      epithelial border. In the IS, caput and corpus, the reactivity for AQP9 differed
      from those observed in domestic animals. The cauda showed a pattern similar to
      that previously described. These results indicate that AQPs 1 and 9 have reversed
      locations and roles in rams, suggesting activity variations related with fluid
      and solute absorption throughout the epididymis. 

PMID- 25976238
TI  - Phenobarbital versus morphine in the management of neonatal abstinence syndrome,
      a randomized control trial.
AB  - BACKGROUNDS: Evaluating the efficacy of the loading and tapering dose of
      Phenobarbital versus oral Morphine in the management of NAS. METHODS: This
      randomized, open-label, controlled trial was conducted on 60 neonates born to
      illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran,
      Iran, who exhibited NAS requiring medical therapy. The neonates were randomized
      to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital
      followed by a tapering dose. The duration of treatment required for NAS
      resolution, the total hospital stay and the requirement for additional second
      line treatment were compared between the treatment groups. RESULTS: The Mean +/-
      Standard Deviation for the duration of treatment required for the resolution of
      NAS was 8.5 +/- 5 days in the Morphine group and 8.5 +/- 4 days in the
      Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 +/-
      5.6 days in the Morphine group and 12.5 +/- 5.3 days in the Phenobarbital group
      (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group
      required adjunctive treatment (P = 0.5). CONCLUSIONS: There were no significant
      differences in the duration of treatment, duration of hospital stay, and the
      requirement for adjunctive treatment, between the neonates with NAS who received
      Morphine Sulfate and neonates who received a loading and tapering dose of
      Phenobarbital. TRIAL REGISTRATION: This study is registered at the Iranian
      Registry of Clinical Trials ( www.irct.ir ) which is a Primary Registry in the
      WHO Registry Network. (Registration Number =  IRCT201406239568N8 ).

PMID- 25976239
TI  - Current knowledge of prenatal diagnosis of mosaic autosomal trisomy in
      amniocytes: karyotype/phenotype correlations.
AB  - Genetic counseling for prenatal diagnosis of autosomal trisomy is complex because
      of the uncertainty of outcome, which is important for management decisions.
      Compilation of cases of prenatally diagnosed autosomal trisomies in amniocytes
      has been done previously in an attempt to elucidate the clinical phenotype of
      these pregnancies. It has been greater than a decade since these studies were
      completed. To update this work, we reviewed cases reported in the literature
      since that time. These cases are correlated with the prior reports to increase
      knowledge about outcomes and to hopefully improve the data available for genetic
      counseling. The risk of abnormal outcome can be summarized as: very high risk
      (>60%) for 47,+2/46; 47,+9/46; 47,+16/46; 47,+20/46; and 47,+22/46; high risk (40
      59%) for 47,+5/46; 47,+14/46; and 47,+15/46; moderately high risk (20-39%) for
      47,+7/46 47,+12/46; and 47,+17/46; moderate risk (up to 19%) for 47,+6/46 and
      47,+8/46, and none were low risk. 47,+6/46 was originally indeterminate, 47,+7/46
      was originally moderate risk, 47,+9/46 was originally high risk, and 47,+17/46
      was originally low risk.

PMID- 25976240
TI  - Most partial domains in proteins are alignment and annotation artifacts.
AB  - BACKGROUND: Protein domains are commonly used to assess the functional roles and
      evolutionary relationships of proteins and protein families. Here, we use the
      Pfam protein family database to examine a set of candidate partial domains. Pfam
      protein domains are often thought of as evolutionarily indivisible, structurally
      compact, units from which larger functional proteins are assembled; however,
      almost 4% of Pfam27 PfamA domains are shorter than 50% of their family model
      length, suggesting that more than half of the domain is missing at those
      locations. To better understand the structural nature of partial domains in
      proteins, we examined 30,961 partial domain regions from 136 domain families
      contained in a representative subset of PfamA domains (RefProtDom2 or RPD2).
      RESULTS: We characterized three types of apparent partial domains: split domains,
      bounded partials, and unbounded partials. We find that bounded partial domains
      are over-represented in eukaryotes and in lower quality protein predictions,
      suggesting that they often result from inaccurate genome assemblies or gene
      models. We also find that a large percentage of unbounded partial domains produce
      long alignments, which suggests that their annotation as a partial is an
      alignment artifact; yet some can be found as partials in other sequence contexts.
      CONCLUSIONS: Partial domains are largely the result of alignment and annotation
      artifacts and should be viewed with caution. The presence of partial domain
      annotations in proteins should raise the concern that the prediction of the
      protein's gene may be incomplete. In general, protein domains can be considered
      the structural building blocks of proteins.

PMID- 25976241
TI  - An Assessment of HIV-Infected Patients Dying in Care for Deceased Organ Donation
      in a United States Urban Center.
AB  - Organ transplantation is an acceptable option for human immunodeficiency virus
      (HIV)-infected patients with end-stage kidney or liver disease. With worse
      outcomes on the waitlist, HIV-infected patients may actually be
      disproportionately affected by the organ shortage in the United States. One
      potential solution is the use of HIV-infected deceased donors (HIVDD), recently
      legalized by the HIV Organ Policy Equity (HOPE) Act. This is the first analysis
      of patient-specific data from potential HIVDD, retrospectively examining charts
      of HIV-infected patients dying in care at six HIV clinics in Philadelphia,
      Pennsylvania from January 1, 2009 to June 30, 2014. Our data suggest that there
      are four to five potential HIVDD dying in Philadelphia annually who might yield
      two to three kidneys and three to five livers for transplant. Extrapolated
      nationally, this would approximate 356 potential HIVDD yielding 192 kidneys and
      247 livers annually. However, several donor risk indices raise concerns about the
      quality of kidneys that could be recovered from HIVDD as a result of older donor
      age and comorbidities. On the other hand, livers from these potential HIVDD are
      of similar quality to HIV-negative donors dying locally, although there is a high
      prevalence of positive hepatitis C antibody. 

PMID- 25976242
TI  - GCKR polymorphism influences liver fat content in patients with type 2 diabetes.
AB  - AIMS: It has recently been shown that an allele in the glucokinase regulatory
      protein (GCKR) gene was associated with increased liver fat content in obese
      children. In this study, we set out to determine whether GCKR rs1260326
      polymorphism was associated with liver fat content in patients with type 2
      diabetes. METHODS: Three hundred and eight patients with type 2 diabetes were
      included in this study. Liver fat content was evaluated using 1H-MR spectroscopy.
      RESULTS: In our population, carriers of the rs1260326 minor T allele had a higher
      liver fat content than did carriers of the C allele homozygote (12.4 +/- 9.6 vs.
      10.3 +/- 9.1 %, p = 0.03). The number of patients with steatosis was
      significantly higher in minor T allele carriers than in C allele homozygote
      carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive
      variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval
      (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p =
      0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and
      rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01].
      CONCLUSIONS: This study shows that in patients with type 2 diabetes who were not
      selected for liver abnormalities, liver fat content was related to GCKR rs1260326
      polymorphism independent of BMI, triglyceride levels, and age.

PMID- 25976243
TI  - Evolution of fungal populations in corn silage conserved under polyethylene or
      biodegradable films.
AB  - AIMS: To identify cultivable filamentous fungi before ensiling, after silage
      conservation, in farm-silos covered with two different plastic films
      (polyethylene (PE) vs biodegradable (MB)), as well as after aerobic exposure of
      whole-crop corn silage. METHODS AND RESULTS: Molecular techniques coupled with
      traditional microbial counting were utilized to identify the predominant fungal
      species. The cultivable fungal population changed remarkably from harvesting to
      silo opening. Anaerobiosis and low pH reduced mould count and the presence of
      Fusarium species both under PE and MB film. However, in the peripheral areas of
      the silo, where air penetration could not be completely prevented, the fungal
      population did not decrease. The predominant fungal species after aerobic
      exposure of silage was Aspergillus fumigatus, without differences between the two
      plastic films. CONCLUSIONS: Maintenance of anaerobiosis and a low pH also in the
      upper layer of the silo reduce the risk of mould growth during corn silage feed
      out. SIGNIFICANCE AND IMPACT OF THE STUDY: Even if the new MB plastic film did
      not completely maintain the anaerobiosis in the upper layer of silage, the
      overall silage quality was not compromised and was similar to that observed under
      PE, indicating that the development and use of MB film to cover silage is
      promising, but needs some improvement.

PMID- 25976244
TI  - Early Miocene elevation in northern Tibet estimated by palaeobotanical evidence.
AB  - The area and elevation of the Tibetan Plateau over time has directly affected
      Asia's topography, the characteristics of the Asian monsoon, and modified global
      climate, but in ways that are poorly understood. Charting the uplift history is
      crucial for understanding the mechanisms that link elevation and climate
      irrespective of time and place. While some palaeoelevation data are available for
      southern and central Tibet, clues to the uplift history of northern Tibet remain
      sparse and largely circumstantial. Leaf fossils are extremely rare in Tibet but
      here we report a newly discovered early Miocene barberry (Berberis) from
      Wudaoliang in the Hoh-Xil Basin in northern Tibet, at a present altitude of 4611
      +/- 9 m. Considering the fossil and its nearest living species probably occupied
      a similar or identical environmental niche, the palaeoelevation of the fossil
      locality, corrected for Miocene global temperature difference, is estimated to
      have been between 1395 and 2931 m, which means this basin has been uplifted ~2-3
      km in the last 17 million years. Our findings contradict hypotheses that suggest
      northern Tibet had reached or exceeded its present elevation prior to the
      Miocene. 

PMID- 25976245
TI  - Molecular and Genomic Alterations in Glioblastoma Multiforme.
AB  - In recent years, important advances have been achieved in the understanding of
      the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic
      alterations and genomic profiles, which recurrently involve multiple signaling
      pathways, have been defined, leading to the first molecular/genetic
      classification of the disease. In this regard, different genetic alterations and
      genetic pathways appear to distinguish primary (eg, EGFR amplification) versus
      secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target
      distinct combinations of the growth factor receptor-ras signaling pathways, as
      well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT,
      retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse
      double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present
      features associated with key stages of normal neurogenesis and (normal) central
      nervous system cell types. This translates into well-defined genomic profiles
      that have been recently classified by The Cancer Genome Atlas Consortium into
      four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review
      the most relevant genetic alterations of primary versus secondary GBM, the
      specific signaling pathways involved, and the overall genomic profile of this
      genetically heterogeneous group of malignant tumors. 

PMID- 25976246
TI  - Postinfarction Cardiac Remodeling Proceeds Normally in Granulocyte Colony
      Stimulating Factor Knockout Mice.
AB  - Treatment with granulocyte colony-stimulating factor (G-CSF) reportedly mitigates
      postinfarction cardiac remodeling and dysfunction. We herein examined the effects
      of G-CSF knockout (G-CSF-KO) on the postinfarction remodeling process in the
      hearts of mice. Unexpectedly, the acute infarct size 24 hours after ligation was
      similar in the two groups. At the chronic stage (4 weeks later), there was no
      difference in the left ventricular dimension, left ventricular function, or
      histological findings, including vascular density, between the two groups. In
      addition, expression of vascular endothelial growth factor (VEGF) was markedly up
      regulated in hearts from G-CSF-KO mice, compared with wild-type mice. Microarray
      failed in detecting up-regulation of VEGF mRNA, whereas G-CSF administration
      significantly decreased myocardial VEGF expression in mice, indicating that G-CSF
      post-transcriptionally down-regulates VEGF expression. When G-CSF-KO mice were
      treated with an anti-VEGF antibody (bevacizumab), cardiac remodeling was
      significantly aggravated, with thinning of the infarct wall and reduction of the
      cellular component, including blood vessels. In the granulation tissue of
      bevacizumab-treated hearts 4 days after infarction, vascular development was
      scarce, with reduced cell proliferation and increased apoptosis, which likely
      contributed to the infarct wall thinning and the resultant increase in wall
      stress and cardiac remodeling at the chronic stage. In conclusion, overexpression
      of VEGF may compensate for the G-CSF deficit through preservation of cellular
      components, including blood vessels, in the postinfarction heart. 

PMID- 25976248
TI  - Induction of Canonical Wnt Signaling by Synovial Overexpression of Selected Wnts
      Leads to Protease Activity and Early Osteoarthritis-Like Cartilage Damage.
AB  - Proteins from the Wnt signaling pathway are very important for joint development.
      Curiously, osteoarthritis (OA) is thought to be a recapitulation of developmental
      processes. Various members of the Wnt signaling pathway are overexpressed in the
      synovium during experimental OA. Here, we investigated the potency of specific
      Wnt proteins, when expressed in the synovium, to induce OA pathology. We
      overexpressed Wnt5a, Wnt8a, Wnt16, and WISP1 in the synovium using adenoviral
      vectors. We determined whether overexpression resulted in OA pathology by
      histology, and we measured whether Wnt signaling led to increased protease
      activity in the joint. Synovial overexpression of Wnt8a and Wnt16 led to
      canonical Wnt signaling in the cartilage, whereas overexpression of Wnt5a did
      not. Canonical Wnt signaling increased protease activity and induced cartilage
      damage shortly after overexpression. Specific blocking of the canonical Wnt
      signaling pathway with Dickkopf-1 reduced the Wnt-signaling-induced cartilage
      damage. By contrast, the noncanonical signaling Wnt5a did not cause cartilage
      lesions. Overexpression of WISP1, a downstream protein of canonical Wnt
      signaling, resulted in increased cartilage damage. In conclusion, our data show
      that canonical Wnts and WISP1, which we found overexpressed in the synovium
      during experimental OA, may conduce to OA pathology.

PMID- 25976249
TI  - Restoration of Functional Glycosylation of alpha-Dystroglycan in FKRP Mutant Mice
      Is Associated with Muscle Regeneration.
AB  - Mutations in fukutin-related protein (FKRP) gene are characterized with lack of
      functionally glycosylated alpha-dystroglycan (F-alpha-DG). Surprisingly, a few
      muscle fibers express strong F-alpha-DG. Herein, we investigated the restoration
      of F-alpha-DG in the FKRP mutant muscles and showed that the restoration of
      glycosylation is associated with muscle regeneration and dependent on the
      expression of both like-glycosyltransferase (LARGE) and partially functional
      FKRP. F-alpha-DG in the regenerating fibers reaches up to normal levels and lasts
      for >4 weeks, but no up-regulation of the LARGE and FKRP is detected during the
      regeneration process. The FKRP protein with P448L mutation is sufficient for
      functional glycosylation of alpha-DG in regenerating fibers, but not in mature
      fibers. Thus, factors other than FKRP enable regenerating fibers to produce
      functional alpha-DG, compensating for the defect in FKRP function. Identification
      of factors other than LARGE and FKRP could generate new approaches for
      restoration of F-alpha-DG in mature muscle fibers with defects in FKRP functions.

PMID- 25976250
TI  - The Patient Protection and Affordable Care Act's Effect on Emergency Medicine: A
      Synthesis of the Data.
AB  - This review synthesizes the existing literature to provide evidence-based
      predictions for the future of emergency care in the United States as a result of
      the Patient Protection and Affordable Care Act, with a focus on emergency
      department (ED) visit volume, acuity, and reimbursement. Patient behavior will
      likely be quite different for patients gaining Medicaid than for those gaining
      private insurance through the Marketplaces. Despite the threat of the individual
      mandate, not all uninsured patients will enroll, and those who choose to enroll
      will likely be a different population from those who remain uninsured. New
      Medicaid enrollees will be a sicker population and will likely increase their
      number of ED visits substantially. Their acuity will be higher at first but will
      then revert to the traditionally high number of low-acuity visits made by
      Medicaid patients. Most patients enrolling through the Marketplace are choosing
      high-deductible health plans, and they will initially avoid the ED because of
      high out-of-pocket costs but may present later and sicker after self-rationing
      their care. Most patients gaining health coverage through the Affordable Care Act
      will be shifting from uninsured to either Medicaid or private insurance, both of
      which reimburse more than self-pay, so ED collections should increase. Because of
      the differences between Medicaid and Marketplace plans, there will be a
      difference in ED volume, acuity, and financial outcomes, depending on states'
      current demographics, whether states expand Medicaid, and how aggressively states
      advertise new options for coverage in Medicaid or state health insurance
      Marketplaces.

PMID- 25976251
TI  - MTA-B or not to be? Recycled bifaces and shifting hunting strategies at Le
      Moustier and their implication for the late Middle Palaeolithic in southwestern
      France.
AB  - Explaining late Middle Palaeolithic industrial variability remains a topic of
      great interest for researchers focusing on aspects of Neanderthal behavioural
      complexity and the so-called Middle-to-Upper Paleolithic 'transition.' Several
      sites in southwestern France figure prominently in these discussions, including
      the eponymous site of Le Moustier (Dordogne, France), one of the 'key' sequences
      used in larger anthropological models. Here we present a re-assessment of this
      important site based on a technological and taphonomic re-evaluation of
      previously studied collections combined with an analysis of unpublished
      archaeological material, which includes both lithic and faunal components. Our
      study produces a very different interpretation of the 'classic' Le Moustier
      sequence, challenging previous cultural attributions in a way that significantly
      impacts current debates surrounding the proposed Mousterian of Acheulean
      Tradition (MTA)--Chatelperronian affiliation. This new interpretation highlights
      independent changes in lithic technology and subsistence strategies that were
      previously undetected as well as a novel aspect of Neanderthal raw material use.
      Finally, we discuss how this new vision has important ramifications for broader
      issues connected to the definition of late Mousterian techno-complexes, such as
      the MTA, and the identification of relationships between technology, subsistence,
      and mobility strategies.

PMID- 25976247
TI  - Intestinal Antigen-Presenting Cells: Key Regulators of Immune Homeostasis and
      Inflammation.
AB  - The microbiota that populate the mammalian intestine are critical for proper host
      physiology, yet simultaneously pose a potential danger. Intestinal antigen
      presenting cells, namely macrophages and dendritic cells (DCs), are integral
      components of the mucosal innate immune system that maintain co-existence with
      the microbiota in face of this constant threat. Intestinal macrophages and DCs
      integrate signals from the microenvironment to orchestrate innate and adaptive
      immune responses that ultimately lead to durable tolerance of the microbiota.
      Tolerance is not a default response, however, because macrophages and DCs remain
      poised to vigorously respond to pathogens that breach the epithelial barrier. In
      this review, we summarize the salient features of macrophages and DCs in the
      healthy and inflamed intestine and discuss how signals from the microbiota can
      influence their function.

PMID- 25976252
TI  - Subcutaneous injection of thymopentin in the area of the supramammary lymph node
      to reduce milk somatic cell count in subclinically mastitic cows.
AB  - The objective of this study was to evaluate the therapeutic effects of
      thymopentin (TP-5) injections on subclinical intramammary infection (IMI) in
      lactating cows. In Experiment I, 40 cows were randomly divided into four groups.
      The cows in groups 1, 2, and 3 received subcutaneous injections of TP-5 in the
      region of the supramammary lymph node at doses of 1, 2, and 4 mg, respectively,
      for 3 days. In Experiment II, 20 cows were randomly divided into two groups. The
      cows in group 1 were treated with injections of TP-5 (4 mg) for 3 days in the
      same area as in Experiment I. Group 4 in Experiment I and group 2 in Experiment
      II were not treated and served as control groups. Milk samples were collected
      before and after treatment for bacteriological examination and analysis of the
      somatic cell count and level of N-acetyl-beta-d-glucosaminidase (NAGase). The
      results showed that treatment with TP-5 significantly reduced the somatic cell
      count (SCC) and NAGase activity of the milk and numerically reduced IMI. A dose
      of 4 mg was found to be optimal for the reduction of SCC and NAGase in milk.
      Therefore, further study of the use of TP-5 in the treatment of bovine mastitis
      is warranted.

PMID- 25976253
TI  - Letter from the new editor.

PMID- 25976254
TI  - Emerging Molecularly-Targeted Therapeutic Strategies in Brain Cancer.
      Introduction.

PMID- 25976255
TI  - Medulloblastoma: toward biologically based management.
AB  - Medulloblastoma is the most common malignant brain tumor in children and, as
      such, has been the focus of tremendous efforts to genomically characterize it.
      What was once thought to be a single disease has been divided into multiple,
      molecularly unique subgroups through gene expression profiling. Each subgroup is
      not only unique in its origin and pathogenesis but also in the prognosis and
      potential therapeutic options. Targeted therapy of malignancies has long been the
      goal of clinical oncology. The progress made in the classification of
      medulloblastoma should be used as a model for future studies. With the evolution
      of epigenetic and genomic sequencing, especially when used in tandem with high
      throughput pharmacologic screening protocols, the potential for subgroup-specific
      targeting is closer than ever. This review focuses on the development of the
      molecular classification system and its potential use in developing prognostic
      models as well as for the advancement of targeted therapeutic interventions. 

PMID- 25976256
TI  - Emerging interplay of genetics and epigenetics in gliomas: a new hope for
      targeted therapy.
AB  - Diffusely infiltrating gliomas are inherently heterogeneous tumors, and there are
      ongoing efforts to establish a classification scheme that incorporates new
      molecular and traditional histologic features. In less than a decade, high
      throughput sequencing of gliomas has transformed the field, uncovering several
      pivotal, highly prevalent genetic alterations that stratify patients into
      different prognostic and treatment-response categories. We highlight the genetic
      aberrations recently discovered in isocitrate dehydrogenase, alpha
      thalassemia/mental retardation syndrome X-linked, death-domain-associated
      protein, histone H3.3, and telomerase reverse transcriptase and discuss how these
      mutations lead to unexpected changes in the epigenetic landscape in gliomas. We
      describe the opportunities these discoveries might provide for the development of
      novel targeted therapy aimed at reversing early epigenetic aberrations in glioma
      precursor cells. Finally, we discuss the challenges for effective treatment of
      this fatal disease posed by intratumoral heterogeneity and clonal evolution. 

PMID- 25976257
TI  - Therapeutic targets in pilocytic astrocytoma based on genetic analysis.
AB  - Pilocytic astrocytoma (PA) is the most common astrocytic neoplasm of childhood.
      Patients have an extremely favorable prognosis after surgical resection,
      qualifying tumors for a grade I designation by the World Health Organization. The
      molecular data on PA support a key role for the BRAF oncogene in the pathogenesis
      of these tumors, with the KIAA1549-BRAF fusion being the most common alteration
      identified in sporadic cases, particularly those occurring in the posterior
      fossa. Constitutive activation of BRAF leads to downstream activation of the
      MEK/MAPK/ERK/p16 pathway, which interestingly is also used by cells to activate
      oncogene-induced senescence (OIS). In fact, the presence of an active OIS pathway
      might explain the periods of dormancy or spontaneous regression or both, that can
      be seen in PA. In addition to reviewing the historical evolution,
      clinicopathologic, predictive, prognostic, and molecular features of PA, we
      discuss current therapeutic strategies and the caveats that should be considered
      for the development of therapies that could be used to more effectively treat
      challenging cases. Individualized treatment requires identification of the type
      of MAPK alteration, as several alterations in BRAF have been described in
      addition to the KIAA1549-BRAF fusion. Combination regimens would also appear
      crucial to achieve tumor eradication and prevent the development of drug
      resistance. Balancing mitogen-activated protein kinases (MAPK) pathway inhibition
      with abrogation of an active OIS should be carefully considered as well to
      preserve any existing protective pathways. Importantly, PAs are largely indolent
      tumors, and care should be taken to avoid overtreatment, as aggressive therapy
      could cause more harm than good. 

PMID- 25976258
TI  - Approaches toward improving the prognosis of pediatric patients with glioma:
      pursuing mutant drug targets with emerging small molecules.
AB  - Gliomas represent approximately 70% of all pediatric brain tumors, and most of
      these are of astrocytic lineage; furthermore, malignant or high-grade
      astrocytomas account for approximately 20% of pediatric astrocytoma. Treatment
      options for pediatric patients with glioma are limited. Although low-grade
      astrocytomas are relatively slow-growing tumors that can often be cured through
      surgical resection, a significant proportion of cases recur, as such, new
      treatments are desperately needed. This review covers the various approaches that
      are currently being made toward improving the prognosis of pediatric patients
      with glioma by pursuing pediatric-selective mutant drug targets with emerging
      small molecules. 

PMID- 25976259
TI  - Targeting Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL): A
      Promising Therapeutic Strategy in Gliomas.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been
      increasingly studied for the treatment of gliomas. TRAIL has the ability to
      specifically target cancer cells, without any harmful effects on normal cells,
      and induces apoptosis by interacting with specific receptors. Nevertheless,
      resistance mechanisms to TRAIL may occur at different points in the signaling
      pathways of TRAIL-induced apoptosis. Various approaches have been developed to
      overcome TRAIL resistance. Here, we have reviewed the known molecular pathways by
      which TRAIL exerts anticancer activity, possible resistance mechanisms, ways to
      sensitize resistant cancer cells, and finally the current clinical successes or
      limitations of TRAIL-based therapies. 

PMID- 25976260
TI  - Roles and potential clinical applications of intermediate filament proteins in
      brain tumors.
AB  - Intermediate filament (IF) proteins are cytoplasmic and nuclear cytoskeletal
      proteins. Of the ~70 IF proteins, nearly 12 are found in the nervous system,
      where their expression is largely cell-type specific. Astrocytes express glial
      fibrillary acidic protein (GFAP), whereas different neuron types contain
      neurofilament proteins, alpha-internexin, or peripherin. These proteins are often
      downregulated in brain cancer. In addition, brain cancer cells may also contain
      vimentin, nestin, and synemin, which are the IF proteins found in neural
      progenitor cells. In different brain tumor types, the expression of nestin,
      vimentin, and alpha-internexin appears to correlate with the clinical outcome.
      Experimental investigations have also demonstrated that IF proteins have distinct
      roles in specific brain tumor cell behaviors: nestin, for instance, is important
      for the proliferation of glioma cells, whereas synemin also affect their
      mobility. The mechanisms responsible for these effects involve the interaction of
      IF proteins with specific signaling pathways. Synemin, for instance, positively
      regulates glioma cell proliferation by antagonizing protein phosphatase 2A.
      Further evidence for the potential of IF proteins as therapeutic targets derives
      from animal models showing the influence of IF proteins on tumor growth. Nestin
      downregulation, for instance, dramatically reduced intracerebral glioma growth.
      Selective targeted therapies of IFs to date primarily include gene therapy
      approaches using nestin or GFAP gene promoters to drive transgene expression into
      glioma cells. Although attempts to identify small molecules specifically
      antagonizing IF proteins have been unsuccessful to date, it is anticipated that
      the identification of such compounds will be instrumental in expanding
      therapeutic approaches for brain tumors. 

PMID- 25976261
TI  - Emerging microtubule targets in glioma therapy.
AB  - Major advances in the genomics and epigenomics of diffuse gliomas and
      glioblastoma to date have not been translated into effective therapy,
      necessitating pursuit of alternative treatment approaches for these
      therapeutically challenging tumors. Current knowledge of microtubules in cancer
      and the development of new microtubule-based treatment strategies for high-grade
      gliomas are the topic in this review article. Discussed are cellular, molecular,
      and pharmacologic aspects of the microtubule cytoskeleton underlying mitosis and
      interactions with other cellular partners involved in cell cycle progression,
      directional cell migration, and tumor invasion. Special focus is placed on (1)
      the aberrant overexpression of betaIII-tubulin, a survival factor associated with
      hypoxic tumor microenvironment and dynamic instability of microtubules; (2) the
      ectopic overexpression of gamma-tubulin, which in addition to its conventional
      role as a microtubule-nucleating protein has recently emerged as a transcription
      factor interacting with oncogenes and kinases; (3) the microtubule-severing
      ATPase spastin and its emerging role in cell motility of glioblastoma cells; and
      (4) the modulating role of posttranslational modifications of tubulin in the
      context of interaction of microtubules with motor proteins. Specific
      antineoplastic strategies discussed include downregulation of targeted molecules
      aimed at achieving a sensitization effect on currently used mainstay therapies.
      The potential role of new classes of tubulin-binding agents and ATPase inhibitors
      is also examined. Understanding the cellular and molecular mechanisms
      underpinning the distinct behaviors of microtubules in glioma tumorigenesis and
      drug resistance is key to the discovery of novel molecular targets that will
      fundamentally change the prognostic outlook of patients with diffuse high-grade
      gliomas. 

PMID- 25976262
TI  - Malnutrition and neurologic problems among children in the developing world.

PMID- 25976263
TI  - Letter to the editor.

PMID- 25976264
TI  - Comparative analysis of antioxidant, antimicrobiological and cytotoxic activities
      of native and fermented chamomile ligulate flower extracts.
AB  - MAIN CONCLUSION: The work investigated differences in apigenin content, as well
      as in other compounds, and examined the chemical profiles, antioxidant,
      antimicrobial and cytotoxic effects of extracts obtained from native and
      fermented chamomile ligulate flowers. Chamomile (Chamomilla recutita L.) has a
      long history of being used as a medicinal plant due to many health benefits,
      including antiinflammatory, anticancer, antispasmodic, radical-scavenging effects
      and others. Apigenin is recognized as one of the most bioactive phenolic
      compounds in chamomile. In comparison to its bound forms, which include mostly
      apigenin-7-O-beta-glucoside and various acylated forms, the aglycone is
      attributed with much higher bioactivity. Due to this fact, in this work ligulate
      florets of chamomile anthodium were subjected to a fermentation process using
      native chamomile enzymes to hydrolyze bound forms of apigenin to free aglycone.
      The contents of apigenin and apigenin-7-O-beta-glucoside were determined in both
      fermented and nonfermented samples by UHPLC-MS-MS analysis to define the
      efficiency of conversion. After defining their chemical profiles, the extracts of
      fermented and nonfermented chamomile samples were also compared with respect to
      their antioxidant, antimicrobial and cytotoxic effects. The antioxidant effects
      of the obtained extracts were defined by electron spin resonance analysis for
      hydroxyl and superoxide radicals. The antimicrobial activity was defined for
      eight microbial strains, whereas cytotoxic activity was evaluated using two human
      cell lines (human cervix carcinoma and human rhabdomyosarcoma) and murine
      fibroblasts.

PMID- 25976265
TI  - Physiological and biochemical mechanisms of the ornamental Eugenia myrtifolia L.
      plants for coping with NaCl stress and recovery.
AB  - MAIN CONCLUSION: We studied the response of Eugenia myrtifolia L. plants, an
      ornamental shrub native to tropical and subtropical areas, to salt stress in
      order to facilitate the use of these plants in Mediterranean areas for
      landscaping. E. myrtifolia plants implement a series of adaptations to acclimate
      to salinity, including morphological, physiological and biochemical changes.
      Furthermore, the post-recovery period seems to be detected by Eugenia plants as a
      new stress situation. Different physiological and biochemical changes in Eugenia
      myrtifolia L. plants after being subjected to NaCl stress for up to 30 days
      (Phase I) and after recovery from salinity (Phase II) were studied. Eugenia
      plants proved to be tolerant to NaCl concentrations between 44 and 88 mM,
      displaying a series of adaptative mechanisms to cope with salt-stress, including
      the accumulation of toxic ions in roots. Plants increased their root/shoot ratio
      and decreased their leaf area, leaf water potential and stomatal conductance in
      order to limit water loss. In addition, they displayed different strategies to
      protect the photosynthetic machinery, including the limited accumulation of toxic
      ions in leaves, increase in chlorophyll content, changes in chlorophyll
      fluorescence parameters, leaf anatomy and antioxidant defence mechanisms.
      Anatomical modifications in leaves, including an increase in palisade parenchyma
      and intercellular spaces and decrease in spongy parenchyma, served to facilitate
      CO2 diffusion in a situation of reduced stomatal aperture. Salinity produced
      oxidative stress in Eugenia plants as evidenced by oxidative stress parameters
      values and a reduction in APX and ASC levels. Nevertheless, SOD and GSH contents
      increased. The post-recovery period is detected as a new stress situation, as
      observed through effects on plant growth and alterations in chlorophyll
      fluorescence and oxidative stress parameters.

PMID- 25976266
TI  - The social-ecological context of media use and school success.

PMID- 25976267
TI  - Duplicate inferior vena cava filters: more is not always better.
AB  - Duplication of the inferior vena cava (IVC) has been reported in literature. This
      achieves clinical significance in the setting of lower extremity venous
      thromboembolism with a contraindication for anticoagulation. We describe a case
      of lower extremity deep vein thrombosis with duplicate IVC. Anticoagulation was
      contraindicated in this case leading to successful treatment with double IVC
      filters. We conducted a PubMed search for all current English language published
      literature, where filters were placed in the presence of duplicate IVC. We
      suggest that patients with deep vein thrombosis should have an accurate
      assessment of venous anatomy before IVC filter placement. Duplication of IVC,
      although rare, should be considered as this has management implications.

PMID- 25976269
TI  - The uniform chest compression depth of 50 mm or greater recommended by current
      guidelines is not appropriate for all adults.
AB  - OBJECTIVE: This study was conducted to evaluate the appropriateness of the chest
      compression (CC) depth recommended in the current guidelines and simulated
      external CCs, and to characterize the optimal CC depth for an adult by body mass
      index (BMI). METHODS: Adult patients who underwent chest computed tomography as a
      screening test for latent pulmonary diseases in the health care center were
      enrolled in this study. We calculated the internal anteroposterior (AP) diameter
      (IAPD) and external AP diameter (EAPD) of the chest across BMIs (<18.50, 18.50
      24.99, 25.00-29.99, and >=30.00 kg/m(2)) for simulated CC depth. We also
      calculated the residual chest depths less than 20 mm for simulated CC depth.
      RESULTS: There was a statistically significant difference in the chest EAPD and
      IAPD measured at the lower half of the sternum for each BMI groups (EAPD: R(2) =
      0.638, P < .001; IAPD: R(2) = 0.297, P < .001). For one-half external AP CC, 100%
      of the patients, regardless of BMI, had a calculated residual internal chest
      depth less than 20 mm. For one-fourth external AP CC, no patients had a
      calculated residual internal chest depth less than 20 mm. For one-third external
      AP CC, only 6.48% of the patients had a calculated residual internal chest depth
      less than 20 mm. CONCLUSIONS: It is not appropriate that the current CC depth
      (>=50 mm), expressed only as absolute measurement without a fraction of the depth
      of the chest, is applied uniformly in all adults. In addition, in terms of safety
      and efficacy, simulated CC targeting approximately between one-third and one
      fourth EAPD CC depth might be appropriate.

PMID- 25976268
TI  - A smoking cessation intervention for low-income smokers in the ED.
AB  - BACKGROUND: There is a high prevalence of smoking among caregivers who bring
      their children to the pediatric emergency department (PED) and even higher rates
      of tobacco smoke exposure (TSE) and related morbidity among their children. The
      PED visit presents an opportunity to intervene with caregivers, but it is unknown
      whether they are more likely to quit if their child has a TSE-related illness. We
      sought to examine a PED-based smoking cessation intervention and compare outcomes
      based on children's TSE-related illness. METHODS: A single-arm, prospective
      trial, with baseline, 3, and 6 month assessments was used in this study.
      Caregivers whose child had either a TSE-related (n=100) or non-TSE-related
      illness (n=100) were given a brief intervention consisting of counseling,
      referral to the Quitline, and free nicotine replacement therapy. RESULTS:
      Participants were 91.5% female, 50.5% African American, 100% Medicaid recipients,
      30.8 years old, child age mean of 5.5 years, 90% highly nicotine dependent, and
      60.3% and 75.8% allowed smoking in the home and car, respectively. At follow-up
      (65% retention), 80% reported quit attempts at 3 months and 89% between 3 and 6
      months. There were significant decreases in number of cigarettes smoked, time to
      first cigarette, and smoking in the home and car. Quit rates were 12.2% at 3
      months, 14.6% at 6 months, and 7.3% at both time points (50% biochemically
      confirmed). There were no significant differences in outcomes based on children's
      illness. CONCLUSIONS: A brief PED-based smoking cessation intervention resulted
      in quit attempts and successful quits. However, the presence of a TSE-related
      illness did not result in different cessation outcomes.

PMID- 25976271
TI  - Subtraction suppressive hybridisation analysis of differentially expressed genes
      associated with puberty in the goat hypothalamus.
AB  - The cost of developing replacement nanny goats could be reduced by decreasing the
      age at puberty because this way nanny goats could be brought into production at
      an earlier age. The aim of the present study was to screen genes related to
      puberty to investigate the molecular mechanisms of puberty. Subtracted cDNA
      libraries were constructed for hypothalami from juvenile (Group A), pubertal
      (Group B) and age-matched control pubertal (Group E) Jining grey (JG) and
      Liaoning cashmere (LC) goats using suppression subtractive hybridisation (SSH).
      Differentially expressed genes were analysed by bioinformatics methods. There
      were 203 expressed sequence tags (ESTs) in the subtracted cDNA libraries that
      were differentially expressed between JG and LC goats at the juvenile stage, 226
      that were differentially expressed at puberty and 183 that were differentially
      expressed in the age-matched control group. The differentially expressed ESTs in
      each subtracted cDNA library were classified as known gene, known EST and unknown
      EST according to sequence homology in the GenBank non-redundant (NR) and EST
      database. According to gene function analysis in the COG (Cluster of Orthologous
      Groups) database, the known genes were grouped into 10 subdivisions in Group A,
      into seven subdivisions in Group E and into nine subdivisions in Group B under
      three categories: cellular processes and signalling, information storage and
      processing, and metabolism. Pathway analysis in the KEGG (Kyoto Encyclopedia of
      Genes and Genomes) pathway database of known genes revealed that the three
      pathways that most differentially expressed genes were involved in were metabolic
      pathways, Parkinson's disease and oxidative phosphorylation. Protein interaction
      analysis of the high homology genes revealed the most dominant network to be
      structure of ribosome/protein translation, oxidative phosphorylation and
      carbohydrate metabolism. The results reveal that the onset of puberty is a
      complex event involving multiple genes in multiple biological processes. The
      differentially expressed genes include genes related to both neuroendocrine and
      energy metabolism.

PMID- 25976270
TI  - Thyrocricotracheal separation with bilateral recurrent laryngeal nerve
      transsection: report of a survivor.
AB  - Thyrocricotracheal separation is an extremely fatal injury that has not been
      reported in the literature. Although timely and proper management of this injury
      is paramount to preserve the patient's life, airway, and voice, its rarity has
      resulted in a lack of consensus regarding the best management option. We report a
      case of thyrocricotracheal separation with bilateral recurrent laryngeal nerve
      transsection caused by a self-inflicted injury, which was treated with
      reanastomosis in conjunction with transverse laser cordotomy. The patient could
      achieve both decannulation and a serviceable voice and could return to a normal
      social life. The present case is the first report of a survivor with
      thyrocricotracheal separation with bilateral recurrent laryngeal nerve
      transsection. This findings show that appropriate management of the airway is the
      first step to ensure a successful outcome, and a step-by-step approach to detect
      and manage the associated injuries is paramount in cases showing the most severe
      form of laryngeal trauma.

PMID- 25976272
TI  - Biomechanical and finite element analyses of bone cement-Injectable cannulated
      pedicle screw fixation in osteoporotic bone.
AB  - The objectives of this study were to investigate the safety and biomechanical
      stability of a polymethylmethacrylate (PMMA)-augmented bone cement-injectable
      cannulated pedicle screw (CICPS) in cancellous bone model, and to analyze the
      stress distribution at the screw-cement-bone interface. The OMEGA cannulated
      pedicle screw (OPS) and conventional pedicle screw (CPS) were used as control
      groups. Safety of the CICPS was evaluated by the static bending and bending
      fatigue tests. Biomechanical stability was analyzed by the maximum axial pullout
      strength and maximum torque tests. Stress distribution at the screw-cement-bone
      interface was analyzed by the finite element (FE) method. The CICPS and CPS
      produced statistically similar values for bending stiffness, bending structural
      stiffness, and bending yield moment. The maximum pullout force was 53.47 +/- 8.65
      N in CPS group, compared to 130.82 +/- 7.32 N and 175.45 +/- 43.01 N in the PMMA
      augmented OPS and CICPS groups, respectively (p < 0.05). The CICPS had a
      significantly greater torque than the OPS and CPS. The FE model did not reveal
      excessive stress at the screw-cement-bone interface in the CICPS group. In
      conclusion, PMMA-augmentation with CICPS may be a potentially useful method to
      increase the stability of pedicle screws in patients with osteoporosis. (c) 2015
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 960-967,
      2016.

PMID- 25976273
TI  - The Role of MicroRNA, miR-24, and Its Target CHI3L1 in Osteomyelitis Caused by
      Staphylococcus aureus.
AB  - Osteomyelitis is a debilitating infectious disease of the bone which is
      predominantly caused by Staphylococcus aureus (S. aureus). MicroRNAs (miRNAs)
      have been shown to play a regulatory role in osteogenesis. In the present study,
      the expression levels of miRNAs proposed to potentially play a regulatory role in
      bone formation or differentiation (miR-24, miR-29b, miR-200a, miR-208, miR-322)
      were analyzed in the whole blood of patients with bacterial osteomyelitis or
      healthy controls, and in MC3T3-E1 cells infected with S. aureus by qRT-PCR. The
      expression of miR-24 was significantly down-regulated in osteomyelitis patients
      and S. aureus-infected MC3T3-E1 cells compared with the healthy controls or
      untreated control cells. Moreover, our results showed that S. aureus inhibited
      MC3T3-E1 cell proliferation, induced osteoblast apoptosis and prohibited bone
      formation and mineralization. We found that overexpression of miR-24 could reduce
      the effects of S. aureus, while inhibition of miR-24 intensified the effects. We
      also demonstrated that miR-24 suppressed the expression of chitinase 3-like 1
      (CHI3L1) mRNA, thought to mediate multiple signaling pathways, by directly
      binding to the 3'-untranslated region.

PMID- 25976274
TI  - Promoting predators and compassionate conservation.

PMID- 25976276
TI  - Research progress of perovskite materials in photocatalysis- and photovoltaics
      related energy conversion and environmental treatment.
AB  - Meeting the growing global energy demand is one of the important challenges of
      the 21st century. Currently over 80% of the world's energy requirements are
      supplied by the combustion of fossil fuels, which promotes global warming and has
      deleterious effects on our environment. Moreover, fossil fuels are non-renewable
      energy and will eventually be exhausted due to the high consumption rate. A new
      type of alternative energy that is clean, renewable and inexpensive is urgently
      needed. Several candidates are currently available such as hydraulic power, wind
      force and nuclear power. Solar energy is particularly attractive because it is
      essentially clean and inexhaustible. A year's worth of sunlight would provide
      more than 100 times the energy of the world's entire known fossil fuel reserves.
      Photocatalysis and photovoltaics are two of the most important routes for the
      utilization of solar energy. However, environmental protection is also critical
      to realize a sustainable future, and water pollution is a serious problem of
      current society. Photocatalysis is also an essential route for the degradation of
      organic dyes in wastewater. A type of compound with the defined structure of
      perovskite (ABX3) was observed to play important roles in photocatalysis and
      photovoltaics. These materials can be used as photocatalysts for water splitting
      reaction for hydrogen production and photo-degradation of organic dyes in
      wastewater as well as for photoanodes in dye-sensitized solar cells and light
      absorbers in perovskite-based solar cells for electricity generation. In this
      review paper, the recent progress of perovskites for applications in these fields
      is comprehensively summarized. A description of the basic principles of the water
      splitting reaction, photo-degradation of organic dyes and solar cells as well as
      the requirements for efficient photocatalysts is first provided. Then, emphasis
      is placed on the designation and strategies for perovskite catalysts to improve
      their photocatalytic activity and/or light adsorption capability. Comments on
      current and future challenges are also provided. The main purpose of this review
      paper is to provide a current summary of recent progress in perovskite materials
      for use in these important areas and to provide some useful guidelines for future
      development in these hot research areas. 

PMID- 25976277
TI  - Improving Flavonoid Bioaccessibility using an Edible Oil-Based Lipid Nanoparticle
      for Oral Delivery.
AB  - To enhance the oral bioaccessibility of flavonoids, including quercetin,
      naringenin, and hesperetin, we prepared an edible oil-based lipid nanoparticle
      (LNP) system. Flavonoid-loaded LNPs were similar to the blank LNP in
      physicochemical characteristics (z average <154.8 nm, polydispersity index <0.17,
      and zeta potential < -40.8 mV), and their entrapment efficiency was >81% at 0.3
      wt % flavonoid concentration of the lipid phase. In the simulated digestion assay
      (mouth, stomach, and small intestine), LNPs were hydrolyzed under small intestine
      conditions and protected successfully incorporated flavonoids (>=94%). Moreover,
      the relative bioaccessibility of flavonoids was >71%, which was otherwise <15%,
      although flavonoids were released rapidly from LNPs into the medium. In
      conclusion, since the flavonoids incorporated in LNPs were preserved well during
      oral digestion and had improved bioaccessibility, the designed LNP system may
      serve as an encapsulation strategy to enhance the bioavailability of
      nonbioaccessible nutraceuticals in foods. 

PMID- 25976278
TI  - VKORC1 -1639 G>A Polymorphism in Romanian Patients With Deep Vein Thrombosis.
AB  - AIM: The purpose of the research was to study the influence of several genetic
      factors, especially the -1693 G>A polymorphism of the VKORC1 gene, on the risk of
      acute unprovoked lower extremity deep vein thrombosis (DVT). MATERIALS AND
      METHODS: The study included 127 patients (median age 63 [53.2; 72] years; 61
      [48%] women and 66 [52%] men) who were diagnosed with acute lower extremity DVT
      and 114 controls (median age 62 [53; 73] years; 64 [56.1%] women and 50 [43.9%]
      men) without DVT. We recorded data regarding the history of DVT and the presence
      of varicose veins. We determined the genotypes for factor V Leiden (FVL)
      mutation, prothrombin G20210A mutation, VKORC1 -1639 G>A mutation, and PAI-1 -675
      4G/5G polymorphism. RESULTS AND CONCLUSION: Varicose veins were found in 67
      (52.8%) patients and 29 (25.4%) controls (P < .001). FVL was present in 29
      (22.8%) patients and 10 (8.8%) controls (P = .005). The VKORC1 (-1693 G>A) GG
      genotype was found in 42 (33.1%) patients and 41 (36%) controls, the GA genotype
      in 71 (55.9%) patients and 47 (41.2%) controls, and AA genotype in 14 (11%)
      patients and 26 (22.8%) controls (P = .020). Multivariate analysis showed that
      the presence of varicose veins, FVL, and VKORC1 -1639 G>A was independently
      associated with the risk of DVT. The VKORC1 (-1693 G>A) AA genotype was
      associated with fewer cases of DVT (odds ratio = 0.435; 95% confidence interval
      0.205-0.991; P = .031).

PMID- 25976279
TI  - Thrombophilia testing in a tertiary paediatric hospital: Indications, outcomes
      and appropriateness.
AB  - AIM: The association between inherited thrombophilia and thrombotic disease in
      children is unclear. As a result, whether expensive thrombophilia tests are
      indicated in children is a contentious issue. This retrospective study aimed to
      assess the appropriateness of thrombophilia testing and the associated cost of
      inappropriate testing at a tertiary paediatric hospital. METHODS: We conducted a
      search for thrombophilia tests ordered at the Royal Children's Hospital between 1
      January 2011 and 31 December 2013. Using pathology and clinical records, we
      collected data relating to demographics, clinical data, indications, requesting
      departments and impact on patient management. RESULTS: Over the 3-year period,
      3867 tests were ordered for 613 patients costing the hospital $102 579. Tests
      were most commonly ordered by gastroenterology on patients receiving liver
      transplants, by neurology as part of the stroke protocol, and by cardiology and
      cardiac surgery for patients anticoagulated on heparin infusions. Testing for
      thrombosis-related indications was relatively uncommon. Thrombophilia testing
      only directly affected management in one-third of patients. Overall, 70% of
      thrombophilia tests ordered were considered appropriate. However, some
      departments were found to have rates of inappropriate testing in excess of 50%.
      CONCLUSION: With improvements in thrombophilia testing practices at the Royal
      Children's Hospital AU$29 645.40 could be saved over 3 years. While there are
      improvements to be made in this area, in the overall context of the hospital's
      pathology testing budget, review of other areas such as inappropriate use of low
      cost, high-volume tests may be of greater value in reducing the cost of pathology
      testing.

PMID- 25976280
TI  - Oral cancer awareness and knowledge among residents in the Oporto city, Portugal.
AB  - OBJECTIVE: To assess the awareness and knowledge on oral cancer in a general
      population of Oporto city, in Portugal. METHODS: Face-to-face interviews were
      performed with 1116 individuals, resident in the city of Oporto. Participants'
      socio-demographic information, lifestyle habits and awareness, knowledge and
      beliefs on oral cancer were ascertained. RESULTS: Breast cancer was the most
      mentioned being as heard of (69.8%), while oral cancer was one of the least heard
      of (23.7%). Tobacco was identified as a risk factor by 54.8% of individuals and
      this knowledge was associated with their education level (P < 0.001), dentist
      visits (P = 0.026), and tobacco consumption (P < 0.001). Fewer subjects (24.6%)
      referred to alcohol as a risk factor, and this knowledge was associated with
      their education level (P = 0.020) and dentist visits (P = 0.002). More than half
      the subjects (58.8%) could not identify any sign or symptom of oral cancer.
      CONCLUSION: There is a general lack of awareness on oral cancer among this Oporto
      population. Higher education level and better oral health care were significant
      factors that identified individuals with a better awareness and knowledge of oral
      cancer, suggesting that educational measures could be useful for the prevention
      and early diagnosis of oral cancer in the Portuguese population.

PMID- 25976281
TI  - Role of immunohistochemistry and fluorescence in-situ hybridization (FISH) in the
      diagnosis of spindle and round cell tumors of the kidney.
AB  - Spindle cell/mesenchymal tumors of the kidney are rare. The diagnosis is
      supported mainly by the application of ancillary techniques such as
      immunohistochemistry (IH) and in-situ hybridization (FISH). An accurate diagnosis
      is essential because early management by complete resection and adjuvant
      chemotherapy improves the prognosis dramatically. Synovial sarcoma and primitive
      neuroectodermal tumor/Ewing sarcoma are infrequent malignancies which usually
      present in soft tissues but rarely in the kidney. The challenge for the
      pathologists is to histologically differentiate between different types of
      sarcomas such as PNET/Ewing's sarcoma, sarcomatous dedifferentiated renal cell
      carcinoma, metastasis, non-Hodgkin's lymphoma, nephroblastoma and angiomyolipoma.
      METHODS: We report from our experience six exemplary rare cases that presented in
      the kidney as spindle/round cell tumors. RESULTS: We have arrived at the accurate
      diagnosis after performing a large panel of IH and FISH. CONCLUSION: In summary
      we advise an immunohistochemical panel for round/spindle cell tumors of the
      kidney and for unclear cases we advise to add (FISH) to get the correct
      diagnosis, as they are completely different regarding surgical approach and post
      operative adjuvant therapy.

PMID- 25976283
TI  - Percutaneous endoscopic gastrostomy (PEG) and pulmonary function in patients with
      amyotrophic lateral sclerosis (ALS).
AB  - In ALS PEG tube placement attenuates malnutrition, secondary to bulbar dysphagia,
      and prevents other frequently fatal complications such as chocking and
      respiratory arrest. Respiratory insufficiency may be associated to the
      complications observed in this procedure. PEG tubes were placed in 26 patients
      (10M/16F) with dysphagia using the Gauderer technique, mild sedatives and local
      anaesthetics. Results are presented in absolute numbers; average; standard
      deviation: Age -26, 64,3+/-11,5; CVF% - 17, 64,5+/-35,6; PaCO2 - 26, 41,6+/-7,1;
      PaO2 - 26, 81,6+/-14,3. Four of the seventeen patients with spirometric
      evaluation had FVC inferior to 50%. Nine patients had chronic respiratory failure
      (CRF). Complications were identified in 2 patients (transient laryngeal spasm)
      and most likely secondary to bulbar involvement rather than pulmonary function.
      CONCLUSION: Our experience shows PEG to be a safe procedure even in patients with
      advanced disease and reduced pulmonary capacity.

PMID- 25976282
TI  - Functional Characterization of Novel Sesquiterpene Synthases from Indian
      Sandalwood, Santalum album.
AB  - Indian Sandalwood, Santalum album L. is highly valued for its fragrant heartwood
      oil and is dominated by a blend of sesquiterpenes. Sesquiterpenes are formed
      through cyclization of farnesyl diphosphate (FPP), catalyzed by metal dependent
      terpene cyclases. This report describes the cloning and functional
      characterization of five genes, which encode two sesquisabinene synthases
      (SaSQS1, SaSQS2), bisabolene synthase (SaBS), santalene synthase (SaSS) and
      farnesyl diphosphate synthase (SaFDS) using the transcriptome sequencing of S.
      album. Using Illumina next generation sequencing, 33.32 million high quality raw
      reads were generated, which were assembled into 84,094 unigenes with an average
      length of 494.17 bp. Based on the transcriptome sequencing, five sesquiterpene
      synthases SaFDS, SaSQS1, SaSQS2, SaBS and SaSS involved in the biosynthesis of
      FPP, sesquisabinene, beta-bisabolene and santalenes, respectively, were cloned
      and functionally characterized. Novel sesquiterpene synthases (SaSQS1 and SaSQS2)
      were characterized as isoforms of sesquisabinene synthase with varying kinetic
      parameters and expression levels. Furthermore, the feasibility of microbial
      production of sesquisabinene from both the unigenes, SaSQS1 and SaSQS2 in non
      optimized bacterial cell for the preparative scale production of sesquisabinene
      has been demonstrated. These results may pave the way for in vivo production of
      sandalwood sesquiterpenes in genetically tractable heterologous systems. 

PMID- 25976284
TI  - Spinal cord lesions - The rehabilitation perspective.
AB  - The present study provides an overview of the spinal cord injury focusing mainly
      on aspects related to rehabilitation. Spinal cord injury affects young people in
      an active phase of life, determining severe handicaps. Most of the lesions are
      traumatic, caused by car accidents. Until fifty years ago, the survival of
      individuals with spinal cord injury was very reduced and the leading cause of
      death was renal failure. Due to developments in medical knowledge and technical
      advances, the survival rates have significantly improved. The causes of death
      have also changed being respiratory complications, particularly pneumonia, the
      leading causes. Immediately after a spinal cord lesion there is a phase of spinal
      shock which is characterized by flaccid paralysis and bladder and bowel
      retention. Progressively there is a return of the spinal cord automatism with the
      beginning of some reflex activities. Based on neurological evaluation it is pos
      sible to predict motor and functional recovery and establish the rehabilitation
      program. We can consider three phases on the rehabilitation program: the first
      while the patient is still in bed, directed to prevent or treat complications due
      to immobility and begin sphincters reeducation; the second phase is intended to
      achieve wheelchair autonomy; the last phase is training in ortostatism. The
      rehabilitation program also comprises sports and recreational activities,
      psychological and social support in order to achieve an integral of the
      individual with a spinal cord injury. 

PMID- 25976285
TI  - Spinal cord injuries functional rehabilitation - Traditional approaches and new
      strategies in physiotherapy.
AB  - Considering the body structures and systems loss of function, after a Spinal Cord
      Injury, with is respective activities limitations and social participation
      restriction, the rehabilitation process goals are to achieve the maximal
      functional independence and quality of life allowed by the clinical lesion. For
      this is necessary a rehabilitation period with a rehabilitation team, including
      the physiotherapist whose interventions will depend on factors such degree of
      completeness or incompleteness and patient clinical stage. Physiotherapy approach
      includes several procedures and techniques related with a traditional model or
      with the recent perspective of neuronal regeneration. Following a traditional
      model, the interventions in complete A and incomplete B lesions, is based on
      compensatory method of functional rehabilitation using the non affected muscles.
      In the incomplete C and D lesions, motor re-education below the lesion, using key
      points to facilitate normal and selective patterns of movement is preferable. In
      other way if the neuronal regeneration is possible with respective function
      improve; the physiotherapy approach goals are to maintain muscular trofism and
      improve the recruitment of motor units using intensive techniques. In both, there
      is no scientific evidence to support the procedures, exists a lack of
      investigation and most of the research are methodologically poor. 

PMID- 25976286
TI  - [Not Available].

PMID- 25976287
TI  - Incidence and risk factors of sepsis mortality in labor, delivery and after
      birth: population-based study in the USA.
AB  - AIM: Maternal sepsis is one of the leading causes of maternal mortality around
      the world. The aim of this study was to estimate the incidence and mortality rate
      of sepsis, and the associated risk factors for their development during
      pregnancy, labor, delivery and the post-partum period. METHODS: We conducted a
      population-based cohort study consisting of 5 million births that occurred in the
      USA. Data were obtained from the Healthcare Cost and Utilization Project
      Nationwide Inpatient Sample (HCUP-NIS) database from 1998 to 2008. Logistic
      regression was used to calculate the adjusted odds ratio and corresponding 95%
      confidence intervals (95%CI) for sepsis development and sepsis-related death
      during admission for delivery. RESULTS: The overall incidence of maternal sepsis
      was 29.4 per 100 000 births (95%CI: 28.0-30.9) with a sepsis case fatality rate
      of 4.4 per 100 births (95%CI: 3.5-5.6). Both the incidence of maternal sepsis and
      sepsis-related death rate have increased over the last decade. Women who are
      black, older than 35 years and who smoke were more likely to experience maternal
      sepsis. An association was also found between maternal sepsis and diabetes
      mellitus, cardiovascular disease, eclampsia, preterm birth, hysterectomy,
      puerperal infection, post-partum hemorrhage, transfusion and chorioamnionitis.
      CONCLUSIONS: Mortality from maternal sepsis during labor and delivery is an
      increasing and important problem in westernized countries. Initiatives aimed at
      improving early recognition and effective management may help reduce the
      occurrence and outcomes of maternal sepsis at time of labor and delivery.

PMID- 25976288
TI  - Physical activity for smoking cessation in pregnancy: randomised controlled
      trial.
AB  - OBJECTIVE: To determine the effectiveness of a physical activity intervention for
      smoking cessation during pregnancy. DESIGN: Parallel group, randomised
      controlled, multicentre trial. SETTING: 13 hospitals in England, April 2009 to
      January 2014. PARTICIPANTS: 789 pregnant smokers, aged 16-50 years and at 10-24
      weeks' gestation, who smoked at least one cigarette daily and were prepared to
      quit smoking one week after enrollment were randomised (1:1); 785 were included
      in the intention to treat analyses, with 392 assigned to the physical activity
      group. INTERVENTIONS: Interventions began one week before a target quit date.
      Participants were randomised to six weekly sessions of behavioural support for
      smoking cessation (control) or to this support plus 14 sessions combining
      supervised treadmill exercise and physical activity consultations. MAIN OUTCOME
      MEASURES: The primary outcome was continuous smoking abstinence from the target
      quit date until end of pregnancy, validated by exhaled carbon monoxide or
      salivary cotinine levels. To assess adherence, levels of moderate-vigorous
      intensity physical activity were self reported and in a 11.5% (n=90) random
      subsample of participants, physical activity was objectively measured by an
      accelerometer. RESULTS: No significant difference was found in rates of smoking
      abstinence at end of pregnancy between the physical activity and control groups
      (8% v 6%; odds ratio 1.21, 95% confidence interval 0.70 to 2.10). For the
      physical activity group compared with the control group, there was a 40% (95%
      confidence interval 13% to 73%), 34% (6% to 69%), and 46% (12% to 91%) greater
      increase in self reported minutes carrying out physical activity per week from
      baseline to one week, four weeks, and six weeks post-quit day, respectively.
      According to the accelerometer data there was no significant difference in
      physical activity levels between the groups. Participants attended a median of
      four treatment sessions in the intervention group and three in the control group.
      Adverse events and birth outcomes were similar between the two groups, except for
      significantly more caesarean births in the control group than in the physical
      activity group (29% v 21%, P=0.023). CONCLUSION: Adding a physical activity
      intervention to behavioural smoking cessation support for pregnant women did not
      increase cessation rates at end of pregnancy. During pregnancy, physical activity
      is not recommended for smoking cessation but remains indicated for general health
      benefits. Trial registration Current Controlled Trials ISRCTN48600346.

PMID- 25976289
TI  - Phylogenetic analysis of HIV-1 subtypes and drug resistance profile among
      treatment-naive people in Kuwait.
AB  - Mutations associated with resistance to antiretroviral therapy are a major cause
      of failure to treatment, and surveillance for the emergence of HIV resistance
      became a component of all antiretroviral treatment programs. As transmission of
      resistant viruses to newly infected persons is possible, we aimed to determine
      the prevalence of primary mutations associated with antiretroviral resistance
      among treatment-naive patients, with respect to HIV subtype. Viral RNA was
      extracted from plasma samples of 43 treatment-naive patients. Protease (PR) and
      reverse transcriptase (RT) regions were amplified and sequenced using the TRUGENE
      HIV-1 Genotyping Assay. A phylogenetic analysis was performed for HIV subtype
      assignment. Complete sequence information could be obtained for 35 patients. A
      total of ten different HIV-1 subtypes and recombinant forms were found in Kuwait
      with predominance of subtypes B, C, and CRF01_AE. A62V and A98G were non
      polymorphic resistance-associated mutations (RAMs) detected in the RT region of
      two and three patients, respectively. Non-polymorphic mutations associated with
      resistance to protease inhibitors were not detected. Our results support
      continuous surveillance of RAMs in newly infected individuals to assess the
      effectiveness of first-line antiretroviral regimen available in Kuwait.

PMID- 25976290
TI  - Influence of Cancer-Associated Endometrial Stromal Cells on Hormone-Driven
      Endometrial Tumor Growth.
AB  - Cancer-associated fibroblasts have been shown to inhibit or stimulate tumor
      growth depending on stage, grade, and tumor type. It remains unclear, however,
      the effect of endometrial-cancer-associated fibroblasts on hormone-driven
      responses in endometrial cancer. In this study, we investigated the effect of
      normal and cancer-associated stromal cells from patients with and without
      endometrial cancer on endometrial tumor growth in response to estradiol (E2) and
      progesterone (P4). Compared to benign endometrial stromal cells, the low-grade
      and high-grade cancer-associated stromal cells exhibited a blunted hormone
      response for proliferation as well as IGFBP1 secretion. Additional analysis of
      the influence of stromal cells on hormone-driven tumor growth was done by mixing
      stromal cells from benign, low-grade, or high-grade tumors, with Ishikawa cells
      for subcutaneous tumor formation. The presence of both benign and high-grade
      cancer-associated stromal cells increased estradiol-driven xenografted tumor
      growth compared to Ishikawa cells alone. Low-grade cancer-associated stromal
      cells did not significantly influence hormone-regulated tumor growth. Addition of
      P4 attenuated tumor growth in Ishikawa + benign or high-grade stromal cells, but
      not in Ishikawa cells alone or with low-grade stromal cells. Using an
      angiogenesis focused real-time array TGFA, TGFB2 and TGFBR1 and VEGFC were
      identified as potential candidates for hormone-influenced growth regulation of
      tumors in the presence of benign and high-grade stromal cells. In summary,
      endometrial-cancer-associated cells responded differently to in vitro hormone
      treatment compared to benign endometrial stromal cells. Additionally, presence of
      stromal cells differentially influenced hormone-driven xenograft growth in vivo
      depending on the disease status of the stromal cells. 

PMID- 25976291
TI  - The Social Appearance Anxiety Scale in Italian Adolescent Populations: Construct
      Validation and Group Discrimination in Community and Clinical Eating Disorders
      Samples.
AB  - Anxiety in situations where one's overall appearance (including body shape) may
      be negatively evaluated is hypothesized to play a central role in Eating
      Disorders (EDs) and in their co-occurrence with Social Anxiety Disorder (SAD).
      Three studies were conducted among community (N = 1995) and clinical (N = 703) ED
      samples of 11- to 18-year-old Italian girls and boys to (a) evaluate the
      psychometric qualities and measurement equivalence/invariance (ME/I) of the
      Social Appearance Anxiety (SAA) Scale (SAAS) and (b) determine to what extent SAA
      or other situational domains of social anxiety related to EDs distinguish
      adolescents with an ED only from those with SAD. Results upheld the one-factor
      structure and ME/I of the SAAS across samples, gender, age categories, and
      diagnostic status (i.e., ED participants with and without comorbid SAD). The SAAS
      demonstrated high internal consistency and 3-week test-retest reliability. The
      strength of the inter-relationships between SAAS and measures of body image,
      teasing about appearance, ED symptoms, depression, social anxiety, avoidance, and
      distress, as well as the ability of SAAS to discriminate community adolescents
      with high and low levels of ED symptoms and community participants from ED
      participants provided construct validity evidence. Only SAA strongly
      differentiated adolescents with any ED from those with comorbid SAD (23.2 %).
      Latent mean comparisons across all study groups were performed and discussed. 

PMID- 25976292
TI  - A phase 1 dosing study of ruxolitinib in children with relapsed or refractory
      solid tumors, leukemias, or myeloproliferative neoplasms: A Children's Oncology
      Group phase 1 consortium study (ADVL1011).
AB  - BACKGROUND: Ruxolitinib, an orally bioavailable JAK1/JAK2 inhibitor, may treat
      cancers with CRLF2 and/or JAK pathway mutations. PROCEDURE: A phase 1 trial of
      ruxolitinib was performed to determine the maximum tolerated or recommended phase
      2 dose, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and
      pharmacodynamics (PD) in children with recurrent/refractory solid tumors (STs).
      Ruxolitinib was administered twice daily (BID) in 28-day cycles at five dose
      levels (15, 21, 29, 39, and 50 mg/m(2)/dose). PK and PD studies were performed
      during cycle 1. Toxicity, preliminary efficacy, and PK/PD were also assessed in
      children with relapsed/refractory hematologic malignancies (HMs). RESULTS: Forty
      nine patients were enrolled, 28 with STs (dose escalation cohort) and 21 with
      HMs. Ruxolitinib was well-tolerated with one DLT per cohort of six patients at
      dose levels (DLs) 2-5. One patient with an ST had grade 5 multi-organ failure at
      DL2. One patient each at DL3 and DL4 had a grade 4 neutropenia, and one patient
      at DL5 had a grade 4 creatinine phosphokinase elevation. No objective responses
      were observed in patients with STs. One patient with polycythemia vera achieved a
      partial response and received 18 cycles of ruxolitinib. The PK of ruxolitinib
      were similar to that in adults. Partial inhibition of phosphorylated JAK2, STAT5,
      and S6 was observed in in vitro plasma inhibitory activity PD assay. CONCLUSION:
      Ruxolitinib was well tolerated in children with refractory cancer. The
      recommended phase 2 dose for continuous BID oral administration is 50
      mg/m(2)/dose. Subsequent evaluation of ruxolitinib in combination with cytotoxic
      chemotherapy in children, adolescents, and young adults with JAK-mutant leukemias
      is planned.

PMID- 25976293
TI  - Differential expression pattern of Annexin A6 in chick neural crest and placode
      cells during cranial gangliogenesis.
AB  - The cranial trigeminal and epibranchial ganglia are components of the peripheral
      nervous system that possess an important somatosensory role. These ganglia arise
      from the intermixing and coalescence of two different migratory cell types,
      neural crest cells and neurogenic placodes cells, and thus typify the phenomena
      of cell migration and intercellular interactions for their creation. The
      underlying molecular mechanisms of ganglia formation, however, are still poorly
      understood. To address this, we have analyzed the spatio-temporal expression
      profile of Annexin A6 during chick gangliogenesis, as Annexin proteins play
      important, conserved roles in ganglia development and physiology. We observe
      Annexin A6 protein in cranial neural crest cells prior to, during and after their
      emergence from the neural tube. Fully migratory cranial neural crest cells,
      however, are devoid of Annexin A6. Interestingly, we note Annexin A6 protein in
      trigeminal and epibranchial placode cells as these cells ingress from the
      ectoderm to initiate ganglia formation. This expression is also maintained in the
      sensory placodes later on when they coalesce with neural crest cells to assemble
      the cranial ganglia. These results suggest that the dynamic expression of Annexin
      A6 in various embryonic cell types may allow Annexin A6 to serve distinct
      functions throughout embryonic development. 

PMID- 25976294
TI  - High-dose-rate brachytherapy boost for prostate cancer: Outcomes and
      genitourinary toxicity.
AB  - AIMS: To report disease outcomes and late urinary toxicity profile. To assess the
      impact of changing technique and evolving quality assurance on genitourinary
      toxicity rates. METHODS AND MATERIALS: One hundred eighty patients were treated
      with external beam radiation therapy and high-dose-rate brachytherapy (HDRB) for
      localized intermediate- and high-risk prostate cancer, between December 2002 and
      February 2012. The HDRB technique evolved over the period of this study, from
      19.5 Gy/3 (n = 68), to 17 Gy/2 (n = 40), 18 Gy/2 (n = 39), and most recently 19
      Gy/2 (n = 33). In the two fraction cohort, 68 patients underwent additional
      correction for catheter displacement before each fraction. RESULTS: With a median
      followup of 5.2 years, 5-year freedom from failure was 93.7% for intermediate,
      and 76.0% for high risk patients. The 3- and 6-year cumulative stricture
      incidence for all patients was 7.8% and 15.3%, respectively. There was no
      statistically significant difference in stricture rate for the four dose levels
      used nor between the three fractions and the two fraction technique overall. The
      19 Gy/2 fractionation group had the lowest 3-year stricture rate (3.0%). The
      addition of correction for intrafraction catheter displacement did not result in
      a statistically significant difference in stricture rates, although the severity
      of strictures has been reduced. CONCLUSIONS: Our biochemical control is
      consistent with other similar series. We found no increase in late urinary
      toxicity with a two fraction, two implant HDRB technique compared with three
      fractions. The HDRB dose did not correlate with stricture rates in our series.
      Correction of intra-fraction catheter displacement did not lead to a
      statistically significant reduction in stricture rates, although may have
      mitigated the effects of dose escalation.

PMID- 25976295
TI  - Lentiviral-mediated short hairpin RNA silencing of APE1 suppresses hepatocellular
      carcinoma proliferation and migration: A potential therapeutic target for
      hepatoma treatment.
AB  - Apurinic/apyrimidinic endonuclease-1 (APE1) is a protein involved in DNA repair
      and transcriptional regulation of gene expression. APE1 expression was reported
      to be correlated with poor prognosis in hepatocellular carcinoma (HCC) patients.
      Based on our previous study, we hypothesized that APE1 may be involved in the
      metastatic progression of HCC. Thus, the present study aimed to investigate the
      knockdown effect of APE1 using shRNA in HCC and demonstrate that silencing of
      APE1 in MHCC97-H cells can decrease the oncogenic transforming potential in vitro
      and reduce the growth of HCC tumor xenografts in vivo. Silencing of APE1
      expression decreased the cell proliferation and survival, reduced the cell
      adhesion ability in Matrigel or fibronectin-coated plates and suppressed the cell
      migration and invasion in a Transwell assay of HCC cells. In the xenograft study,
      tumor growth was markedly inhibited in the APE1-silenced group. Silencing of APE1
      in MHCC97-H cells decreased the oncogenic transforming potential in vitro and
      reduced the growth of HCC tumor xenografts in vivo. Inhibition of APE1 may
      present a novel therapeutic approach for the treatment of HCC.

PMID- 25976296
TI  - A Prospective Randomised Phase III Clinical Trial Testing the Role of
      Prophylactic Cranial Radiotherapy in Patients Treated with Trastuzumab for
      Metastatic Breast Cancer - Anglo Celtic VII.
AB  - A high incidence of central nervous system (CNS) metastases has been reported in
      patients with HER2-positive tumours receiving trastuzumab therapy for metastatic
      breast cancer. This study tested whether prophylactic cranial irradiation (PCI)
      could reduce the incidence of CNS metastases in this setting. This was a
      prospective, randomised phase III trial. Patients were randomised 1:1 to no PCI
      or PCI delivered at around 6 weeks after study entry. Cognitive function was
      assessed prospectively. In total, 51 patients were randomised over a 3 year
      period; 25 received PCI and 26 did not. The cumulative incidence of CNS
      metastases at 2 years was 32.4% (standard error = 9.8%) on the no PCI arm and
      21.0% (standard error = 8.6%) on the PCI arm; the associated hazard ratio was
      0.57 (95% confidence interval 0.18-1.74; P = 0.32). There was no evidence of
      cognitive dysfunction in PCI patients.

PMID- 25976298
TI  - Early childhood development of visual texture segregation in full-term and
      preterm children.
AB  - To date, very little is known about the normal development trajectory of visual
      texture segregation, or how it is affected by preterm birth. The goal of this
      study was to characterize the development of visual texture segregation using
      texture segregation visual evoked potentials (tsVEPs) in children born full-term
      and children born preterm without major neurological impairment. Forty-five full
      term and 43 preterm children were tested at either 12, 24 or 36 months of age
      (corrected age for prematurity at 12 and 24 months old). VEPs were obtained using
      two lower-level stimuli defined by orientation (oriVEP) and two higher-level
      stimuli defined by texture (texVEP). TsVEP was obtained by dividing by two the
      subtraction of oriVEP from texVEP. Results show a clear maturation of the
      processes underlying visual texture segregation in the full-term group, with a
      significant N2 latency reduction between 12 and 36 months of age for all
      conditions. Significant N2 amplitude reduction was observed for oriVEP between 12
      and 24 months, as well as for texVEP between 12 and 24 months, and 12 and 36
      months. Comparison between full-term and preterm children indicated significantly
      lower N2 amplitude for the preterm group at 12 months for oriVEP and texVEP.
      These differences were no longer apparent at 24 months of age, suggesting that
      children born preterm catch up with their full-term counterparts somewhere
      between 12 and 24 months of age. Our results appear to reflect a maturational
      delay in preterm children in both lower-level and higher-level visual processing
      during, at least, early childhood.

PMID- 25976299
TI  - Onset of background dynamic noise attenuates preview benefit in inefficient
      visual search.
AB  - When certain distractors (old items) appear before others (new items) during an
      inefficient visual search task, observers exclude the old items from the search
      (preview benefit), possibly because their locations are deprioritized relative to
      the locations of the new items. We examined whether participants were able to
      ignore task-irrelevant changes in a scene (i.e., the onset of repetitive changes,
      continual repetitive changes, and the cessation of repetitive changes in the
      background), while performing a preview search task. The results indicated that,
      when the noise continually changed position throughout each trial, or when
      dynamic noise was changed to static noise simultaneous with the appearance of the
      search display, the preview benefit remained. In contrast, when the static
      background noise was changed to dynamic background noise, simultaneous with the
      appearance of the search display, this task-irrelevant background event abolished
      the preview benefit on search efficiency. Therefore, we conclude that the onset
      of task-irrelevant repetitive changes in the background disrupts the process of
      inhibitory marking of old items. 

PMID- 25976300
TI  - In vivo protective effect of Uridine, a pyrimidine nucleoside, on genotoxicity
      induced by Levodopa/Carbidopa in mice.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder that affects
      millions of people all over the world. Motor symptoms of PD are most commonly
      controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of
      dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa
      decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a
      combination of Levodopa plus carbidopa has been demonstrated to cause a major
      complication, namely abnormal involuntary movements. On the other hand, the
      effect of this treatment on bone marrow cells is unknown. Therefore, in this
      study, we aimed to investigate possible genotoxic effects of Levodopa and
      Carbidopa using male Balb/C mice. Our results showed that Levodopa alone or in
      combination with carbidopa caused genotoxicity in in vivo micronucleus test
      (mouse bone marrow) and Comet assay (blood cells). Furthermore, we showed that
      simultaneous administration of uridine, a pyrimidine nucleoside, reversed the
      genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the
      first time that Levodopa plus carbidopa combination causes genotoxicity which is
      reversed by uridine treatment. These findings might enhance our understanding for
      the complications of a common Parkinson's treatment and confer benefit in terms
      of reducing a possible genotoxic effect of this treatment. 

PMID- 25976301
TI  - Double decomposition: decomposing the variance in subcomponents of male extra
      pair reproductive success.
AB  - 1. Extra-pair reproductive success (EPRS) is a key component of male fitness in
      socially monogamous systems and could cause selection on female extra-pair
      reproduction if extra-pair offspring (EPO) inherit high value for EPRS from their
      successful extra-pair fathers. However, EPRS is itself a composite trait that can
      be fully decomposed into subcomponents of variation, each of which can be further
      decomposed into genetic and environmental variances. However, such decompositions
      have not been implemented in wild populations, impeding evolutionary inference.
      2. We first show that EPRS can be decomposed into the product of three life
      history subcomponents: the number of broods available to a focal male to sire
      EPO, the male's probability of siring an EPO in an available brood and the number
      of offspring in available broods. This decomposition of EPRS facilitates
      estimation from field data because all subcomponents can be quantified from
      paternity data without need to quantify extra-pair matings. Our decomposition
      also highlights that the number of available broods, and hence population
      structure and demography, might contribute substantially to variance in male EPRS
      and fitness. 3. We then used 20 years of complete genetic paternity and pedigree
      data from wild song sparrows (Melospiza melodia) to partition variance in each of
      the three subcomponents of EPRS, and thereby estimate their additive genetic
      variance and heritability conditioned on effects of male coefficient of
      inbreeding, age and social status. 4. All three subcomponents of EPRS showed some
      degree of within-male repeatability, reflecting combined permanent environmental
      and genetic effects. Number of available broods and offspring per brood showed
      low additive genetic variances. The estimated additive genetic variance in extra
      pair siring probability was larger, although the 95% credible interval still
      converged towards zero. Siring probability also showed inbreeding depression and
      increased with male age, while the numbers of available broods and offspring per
      brood did not. 5. Our results indicate that the probability that a male will sire
      an EPO in an available brood is the primary source of genetic variation in male
      EPRS, implying that the evolution of female extra-pair reproduction could be
      facilitated by genetic covariance with this subcomponent of EPRS.

PMID- 25976302
TI  - Polyethylene recycling: Waste policy scenario analysis for the EU-27.
AB  - This paper quantifies the main impacts that the adoption of the best recycling
      practices together with a reduction in the consumption of single-use plastic bags
      and the adoption of a kerbside collection system could have on the 27 Member
      States of the EU. The main consequences in terms of employment, waste management
      costs, emissions and energy use have been quantified for two scenarios of
      polyethylene (PE) waste production and recycling. That is to say, a "business as
      usual scenario", where the 2012 performances of PE waste production and recycling
      are extrapolated to 2020, is compared to a "best practice scenario", where the
      best available recycling practices are modelled together with the possible
      adoption of the amended Packaging and Packaging Waste Directive related to the
      consumption of single-use plastic bags and the implementation of a kerbside
      collection system. The main results show that socio-economic and environmental
      benefits can be generated across the EU by the implementation of the best
      practice scenario. In particular, estimations show a possible reduction of 4.4
      million tonnes of non-recycled PE waste, together with a reduction of around ?90
      million in waste management costs in 2020 for the best practice scenario versus
      the business as usual scenario. An additional 35,622 jobs are also expected to be
      created. In environmental terms, the quantity of CO2 equivalent emissions could
      be reduced by around 1.46 million tonnes and the net energy requirements are
      expected to increase by 16.5 million GJ as a consequence of the reduction in the
      energy produced from waste. The main analysis provided in this paper, together
      with the data and the model presented, can be useful to identify the possible
      costs and benefits that the implementation of PE waste policies and Directives
      could generate for the EU. 

PMID- 25976297
TI  - Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress.
AB  - In human addicts, drug relapse and craving are often provoked by stress. Since
      1995, this clinical scenario has been studied using a rat model of stress-induced
      reinstatement of drug seeking. Here, we first discuss the generality of stress
      induced reinstatement to different drugs of abuse, different stressors, and
      different behavioral procedures. We also discuss neuropharmacological mechanisms,
      and brain areas and circuits controlling stress-induced reinstatement of drug
      seeking. We conclude by discussing results from translational human laboratory
      studies and clinical trials that were inspired by results from rat studies on
      stress-induced reinstatement. Our main conclusions are (1) The phenomenon of
      stress-induced reinstatement, first shown with an intermittent footshock stressor
      in rats trained to self-administer heroin, generalizes to other abused drugs,
      including cocaine, methamphetamine, nicotine, and alcohol, and is also observed
      in the conditioned place preference model in rats and mice. This phenomenon,
      however, is stressor specific and not all stressors induce reinstatement of drug
      seeking. (2) Neuropharmacological studies indicate the involvement of
      corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate,
      kappa/dynorphin, and several other peptide and neurotransmitter systems in stress
      induced reinstatement. Neuropharmacology and circuitry studies indicate the
      involvement of CRF and noradrenaline transmission in bed nucleus of stria
      terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and
      glutamate transmission in other components of the mesocorticolimbic dopamine
      system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex,
      and nucleus accumbens). (3) Translational human laboratory studies and a recent
      clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in
      decreasing stress-induced drug craving and stress-induced initial heroin lapse. 

PMID- 25976304
TI  - Cytoplasmic translocation, aggregation, and cleavage of TDP-43 by enteroviral
      proteases modulate viral pathogenesis.
AB  - We have previously demonstrated that infection by coxsackievirus B3 (CVB3), a
      positive-stranded RNA enterovirus, results in the accumulation of insoluble
      ubiquitin-protein aggregates, which resembles the common feature of
      neurodegenerative diseases. The importance of protein aggregation in viral
      pathogenesis has been recognized; however, the underlying regulatory mechanisms
      remain ill-defined. Transactive response DNA-binding protein-43 (TDP-43) is an
      RNA-binding protein that has an essential role in regulating RNA metabolism at
      multiple levels. Cleavage and cytoplasmic aggregation of TDP-43 serves as a major
      molecular marker for amyotrophic lateral sclerosis and frontotemporal lobar
      degeneration and contributes significantly to disease progression. In this study,
      we reported that TDP-43 is translocated from the nucleus to the cytoplasm during
      CVB3 infection through the activity of viral protease 2A, followed by the
      cleavage mediated by viral protease 3C. Cytoplasmic translocation of TDP-43 is
      accompanied by reduced solubility and increased formation of protein aggregates.
      The cleavage takes place at amino-acid 327 between glutamine and alanine,
      resulting in the generation of an N- and C-terminal cleavage fragment of ~35 and
      ~8 kDa, respectively. The C-terminal product of TDP-43 is unstable and quickly
      degraded through the proteasome degradation pathway, whereas the N-terminal
      truncation of TDP-43 acts as a dominant-negative mutant that inhibits the
      function of native TDP-43 in alternative RNA splicing. Lastly, we demonstrated
      that knockdown of TDP-43 results in an increase in viral titers, suggesting a
      protective role for TDP-43 in CVB3 infection. Taken together, our findings
      suggest a novel model by which cytoplasmic redistribution and cleavage of TDP-43
      as a consequence of CVB3 infection disrupts the solubility and transcriptional
      activity of TDP-43. Our results also reveal a mechanism evolved by enteroviruses
      to support efficient viral infection. 

PMID- 25976303
TI  - PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A
      and Protein Kinase C signaling.
AB  - A synthetic peptide (sPIF) analogous to the mammalian embryo-derived
      PreImplantation Factor (PIF) enables neuroprotection in rodent models of
      experimental autoimmune encephalomyelitis and perinatal brain injury. The
      protective effects have been attributed, in part, to sPIF's ability to inhibit
      the biogenesis of microRNA let-7, which is released from injured cells during
      central nervous system (CNS) damage and induces neuronal death. Here, we uncover
      another novel mechanism of sPIF-mediated neuroprotection. Using a clinically
      relevant rat newborn brain injury model, we demonstrate that sPIF, when
      subcutaneously administrated, is able to reduce cell death, reverse neuronal loss
      and restore proper cortical architecture. We show, both in vivo and in vitro,
      that sPIF activates cyclic AMP dependent protein kinase (PKA) and calcium
      dependent protein kinase (PKC) signaling, leading to increased phosphorylation of
      major neuroprotective substrates GAP-43, BAD and CREB. Phosphorylated CREB in
      turn facilitates expression of Gap43, Bdnf and Bcl2 known to have important roles
      in regulating neuronal growth, survival and remodeling. As is the case in sPIF
      mediated let-7 repression, we provide evidence that sPIF-mediated PKA/PKC
      activation is dependent on TLR4 expression. Thus, we propose that sPIF imparts
      neuroprotection via multiple mechanisms at multiple levels downstream of TLR4.
      Given the recent FDA fast-track approval of sPIF for clinical trials, its
      potential clinical application for treating other CNS diseases can be envisioned.

PMID- 25976306
TI  - Spontaneous rupture of a congenital diaphragmatic eventration in an infant.
AB  - Rupture of the diaphragm may be traumatic or spontaneous. A spontaneous rupture
      occurring in a congenital eventration of the diaphragm is extremely rare. Only
      one such case has been reported previously. We report a case of a 5-month-old
      male infant who presented with acute life-threatening respiratory distress
      secondary to spontaneous rupture of a congenital diaphragmatic eventration. 

PMID- 25976305
TI  - Significant lethality following liver resection in A20 heterozygous knockout mice
      uncovers a key role for A20 in liver regeneration.
AB  - Hepatic expression of A20, including in hepatocytes, increases in response to
      injury, inflammation and resection. This increase likely serves a
      hepatoprotective purpose. The characteristic unfettered liver inflammation and
      necrosis in A20 knockout mice established physiologic upregulation of A20 as
      integral to the anti-inflammatory and anti-apoptotic armamentarium of
      hepatocytes. However, the implication of physiologic upregulation of A20 in
      modulating hepatocytes' proliferative responses following liver resection remains
      controversial. To resolve the impact of A20 on hepatocyte proliferation and the
      liver's regenerative capacity, we examined whether decreased A20 expression, as
      in A20 heterozygous knockout mice, affects outcome following two-third partial
      hepatectomy. A20 heterozygous mice do not demonstrate a striking liver phenotype,
      indicating that their A20 expression levels are still sufficient to contain
      inflammation and cell death at baseline. However, usually benign partial
      hepatectomy provoked a staggering lethality (>40%) in these mice, uncovering an
      unsuspected phenotype. Heightened lethality in A20 heterozygous mice following
      partial hepatectomy resulted from impaired hepatocyte proliferation due to
      heightened levels of cyclin-dependent kinase inhibitor, p21, and deficient
      upregulation of cyclins D1, E and A, in the context of worsened liver steatosis.
      A20 heterozygous knockout minimally affected baseline liver transcriptome, mostly
      circadian rhythm genes. Nevertheless, this caused differential expression of
      >1000 genes post hepatectomy, hindering lipid metabolism, bile acid biosynthesis,
      insulin signaling and cell cycle, all critical cellular processes for liver
      regeneration. These results demonstrate that mere reduction of A20 levels causes
      worse outcome post hepatectomy than full knockout of bona fide liver pro
      regenerative players such as IL-6, clearly ascertaining A20's primordial role in
      enabling liver regeneration. Clinical implications of these data are of utmost
      importance as they caution safety of extensive hepatectomy for donation or tumor
      in carriers of A20/TNFAIP3 single nucleotide polymorphisms alleles that decrease
      A20 expression or function, and prompt the development of A20-based liver pro
      regenerative therapies. 

PMID- 25976307
TI  - Association of antithyroid peroxidase antibody with fibromyalgia in rheumatoid
      arthritis.
AB  - To investigate how autoimmune thyroiditis (ATD) affects the clinical presentation
      of established rheumatoid arthritis (RA) with particular reference to
      fibromyalgia and chronic widespread pain (CWP). A cohort of 204 patients with RA
      for whom the presence or absence of autoimmune thyroid antibodies was documented
      was examined for the relationships between thyroid autoantibodies and
      fibromyalgia or CWP. We identified 29 % who tested positive for antithyroid
      peroxidase antibodies (TPOAb). The anti-thyroglobulin antibody (TgAb) was found
      in 24 %. Among the thyroid autoantibody-positive patients, 40 % had a diagnosis
      of fibromyalgia or CWP versus 17 % for antibody negative patients. Logistic
      regression analyses (adjusted by age, sex, diabetes and BMI) indicated that TPOAb
      positive patients were more likely to have fibromyalgia or CWP, with an odds
      ratio (OR) of 4.641, 95 % confidence interval (CI) (2.110-10.207) P < .001.
      Adjusting for spinal degenerative disc disease did not change the association
      with fibromyalgia, OR 4.458, 95 % CI (1.950-10.191), P < .001. The OR between
      TgAb and fibromyalgia was not significant (P > .05). Additional logistic
      regression analyses (adjusted by age, sex and BMI) indicated a significant
      relationship between TPOAb and fibromyalgia or CWP in patients without diabetes
      and those without hypothyroidism (OR of 4.873, 95 % CI (1.877-12.653), P = .001
      and OR of 4.615 95 % CI (1.810-11.770), P = .001, respectively). There may be a
      positive association between the ATD antibody TPOAb, and fibromyalgia syndrome
      and CWP in patients with established RA. 

PMID- 25976308
TI  - An evidence-based warfarin management protocol reduces surgical delay in hip
      fracture patients.

PMID- 25976309
TI  - Dietary Nitrate, Nitric Oxide, and Cardiovascular Health.
AB  - Emerging evidence strongly suggests that dietary nitrate, derived in the diet
      primarily from vegetables, could contribute to cardiovascular health via effects
      on nitric oxide (NO) status. NO plays an essential role in cardiovascular health.
      It is produced via the classical L-arginine-NO-synthase pathway and the recently
      discovered enterosalivary nitrate-nitrite-NO pathway. The discovery of this
      alternate pathway has highlighted dietary nitrate as a candidate for the
      cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials
      with dietary nitrate have observed improvements in blood pressure, endothelial
      function, ischemia-reperfusion injury, arterial stiffness, platelet function, and
      exercise performance with a concomitant augmentation of markers of NO status.
      While these results are indicative of cardiovascular benefits with dietary
      nitrate intake, there is still a lingering concern about nitrate in relation to
      methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this
      review to present an overview of NO and its critical role in cardiovascular
      health; to detail the observed vascular benefits of dietary nitrate intake
      through effects on NO status as well as to discuss the controversy surrounding
      the possible toxic effects of nitrate. 

PMID- 25976311
TI  - Effects of stromal interacting molecule 1 gene silencing by short hairpin RNA on
      the biological behavior of human gastric cancer cells.
AB  - Gastric cancer is one of the most common types of cancer worldwide. It has been
      reported that stromal interacting molecule 1 (STIM1) is associated with tumor
      progression and metastatic spread, including in cervical cancer, breast carcinoma
      and prostatic cancer. The present study investigated whether STIM1, an
      endoplasmic reticulum Ca(2+) sensor and activator of store-operated channel
      entry, contributed to SGC7901 cell progression. The pGPU6-shSTIM1 recombinant
      plasmid was constructed, and the effects of downregulation of STIM1 on the
      proliferation, apoptosis, migration and invasion of SGC7901 cells were examined.
      Western blot analysis revealed that transfection with the pGPU6-shSTIM1 plasmid
      successfully inhibited the expression of STIM1. STIM1 silencing in the gastric
      cancer cells significantly inhibited cell proliferation by arresting the cell
      cycle at the G0/G1 phase, and increasing the apoptotic rate following treatment
      of the SGC7901 cells with pGPU6-shSTIM1, indicated using an MTT cell viability
      assay and flow cytometery, respectively. As expected, STIM1 knock down also
      reduced the migration and invasion of the SGC7901 cells, demonstrated using a
      Transwell assay. The possible molecular mechanism involved the regulation of
      several signaling pathways involved in the biological behavior of cell survival,
      apoptosis, migration and metastasis. Together, these finding suggested that the
      expression of STIM1 is crucial for the proliferation and invasion of SGC7901
      cells, providing a foundation for the development of novel type-specific
      diagnostic strategies and treatments for gastric cancer.

PMID- 25976312
TI  - A Qualitative Exploration of Date Rape Survivors' Physical and Psycho-Social
      Experiences in a Nigerian University.
AB  - Date rape (DR) is a serious but under-recognized public health problem that
      affects female university undergraduates. The burden of the problem in Nigerian
      universities is, however, yet to be fully investigated. The study was designed to
      explore the physical and psycho-social experiences of DR female survivors at the
      University of Ibadan. The study was qualitative in nature and involved eight
      consenting DR survivors. A pre-tested In-Depth Interview (IDI) guide that
      included questions relating to survivors' personal profile, context of DR
      experienced, factors that promoted survivors' vulnerability, reported adverse
      health consequences, help-seeking behaviors, and effects of the rape episode on
      dating relationship was used to facilitate the conduct of the narrative
      interview. The interviews were conducted in accordance to the protocol approved
      by the Joint University of Ibadan and University College Hospital Ethics Review
      Committee, and were taped-recorded and subjected to content analysis.
      Participants' mean age was 17.3 +/- 2.3 years. All the participants were
      teenagers when they were first raped. Coercive and deceptive means were used to
      perpetrate the act of rape. Participants' use of verbal appeals, crying, and
      physical resistance to prevent being raped proved abortive. The experienced
      adverse physical health consequences included vaginal bleeding and injury. Major
      psycho-social effects of the experienced DR included self-blame, depression,
      hatred for men, and suicidal feelings. DR experiences occurred mainly in isolated
      settings, and most participants could not seek for medical help and other forms
      of care due to fear of being stigmatized. Some of the DR survivors continued
      their dating relationships when apologies were tendered by the perpetrators. DR
      is a traumatic experience, which is characterized by physical and psycho-social
      adverse effects. DR survivors, however, rarely seek for help as a result of the
      fear of being stigmatized. Multiple behavioral change interventions are needed to
      address the phenomenon.

PMID- 25976310
TI  - Lack of aprataxin impairs mitochondrial functions via downregulation of the
      APE1/NRF1/NRF2 pathway.
AB  - Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused
      by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin
      (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1
      patients carrying the common W279X mutation, and aprataxin has been localized to
      mitochondria in neuroblastoma cells, where it enhances preservation of
      mitochondrial function. In this study, we show that aprataxin deficiency impairs
      mitochondrial function, independent of its role in mitochondrial DNA repair. The
      bioenergetics defect in AOA1-mutant fibroblasts and APTX-depleted Hela cells is
      caused by decreased expression of SDHA and genes encoding CoQ biosynthetic
      enzymes, in association with reductions of APE1, NRF1 and NRF2. The biochemical
      and molecular abnormalities in APTX-depleted cells are recapitulated by knockdown
      of APE1 in Hela cells and are rescued by overexpression of NRF1/2. Importantly,
      pharmacological upregulation of NRF1 alone by 5-aminoimidazone-4-carboxamide
      ribonucleotide does not rescue the phenotype, which, in contrast, is reversed by
      the upregulation of NRF2 by rosiglitazone. Accordingly, we propose that the lack
      of aprataxin causes reduction of the pathway APE1/NRF1/NRF2 and their target
      genes. Our findings demonstrate a critical role of APTX in transcription
      regulation of mitochondrial function and the pathogenesis of AOA1 via a novel
      pathomechanistic pathway, which may be relevant to other neurodegenerative
      diseases. 

PMID- 25976313
TI  - Experience of Domestic Violence During Childhood, Intimate Partner Violence, and
      the Deterrent Effect of Awareness of Legal Consequences.
AB  - The concept of intergenerational transmission of intimate partner violence (IPV)
      has been an important topic of research. Experts have contended that this brutal
      path in which violence is transmitted to subsequent generations may be avoidable.
      This study examined whether public perceptions of the legal regulation of IPV and
      the certainty of sanction deter the prevalence of IPV. Data from 3,800 households
      were obtained from a nationwide survey conducted in South Korea. Due to a skewed
      distribution of the prevalence of IPV, this study applied a zero-inflated Poisson
      (ZIP) model, which has been shown to address issues of skewed count variables. In
      addition, use of a ZIP model allowed us to examine factors associated with the
      occurrence and frequency of IPV. Results showed that child abuse experience and
      perceptions of the law were associated with the occurrence of IPV. Individuals
      who experienced child abuse were more likely to perpetrate IPV, whereas those
      aware of the law were less likely to perpetrate IPV. Witnessing IPV between
      parents was associated with an increased frequency of IPV. Results suggest that
      by increasing awareness of laws against domestic violence, IPV may be reduced or
      prevented.

PMID- 25976315
TI  - Coercive Control and Physical Violence in Older Adults: Analysis Using Data From
      the National Elder Mistreatment Study.
AB  - The most common perpetrators of physical violence against women of any age are
      their intimate partners. Although research on younger adults has recognized that
      intimate partner violence (IPV) is distinct in etiology, form, and consequence,
      whether the same is true for older adults has not been adequately studied. The
      extent and consequences of coercive controlling violence, IPV that involves
      physical violence coupled with psychological aggression and/or financial abuse,
      have not been examined in older populations. Using data from the National Elder
      Mistreatment Study, the current research examines if coercive control is more
      evident in physical violent victimizations of older adults (age 60 or older) when
      the perpetrator is an intimate partner compared with when the perpetrator is not
      an intimate partner. Findings indicate that older adults who experience emotional
      coercive control by intimate partners in their lifetime are more likely to
      experience physical abuse at age 60 or older. Furthermore, older adults who
      experienced trauma during their lifetime, were in poor health, and with less
      social support are more likely to experience physical abuse at age 60 or older.
      However, the victim's sex had no significant influence on the likelihood of
      experiencing physical abuse.

PMID- 25976314
TI  - Support Schemas Influence Reactivity for Adult Survivors of Childhood
      Maltreatment.
AB  - Adult survivors of childhood maltreatment can be resilient when they have
      adequate psychosocial resources to cope with maltreatment-related sequelae;
      however, interpersonal problems may influence the effectiveness of such
      resources. This study used a schema activation experimental paradigm to test the
      benefit of social support cognitions on emotional reactivity in adult survivors,
      while also testing for the moderating role of interpersonal problems and the
      mediating role of stress appraisal. Young women (N = 126, ages = 18-23) with
      histories of childhood maltreatment were administered an anger provocation
      stressor task while their cardiac activity, state anger, and stress appraisals
      were assessed. Prior to the stressor, women were randomly assigned to either a
      support schema condition or an acquaintance schema (control) condition, in which
      they were asked to think and write about either a supportive person or casual
      acquaintance. The support schema condition demonstrated the least emotional
      reactivity as evidenced by subjective anger and heart-rate variability, and this
      outcome was strongest for those with high interpersonal problems. Also, stress
      appraisals, particularly feeling intimidated, partially mediated the support
      schema and emotional reactivity relationship. These findings suggest that
      maltreated women can regulate anger by activating their social support schema.
      Moreover, support schema may be an important focus of intervention for adult
      survivors with high interpersonal problems.

PMID- 25976317
TI  - Transformation of acidic poorly water soluble drugs into ionic liquids.
AB  - Poor water solubility of active pharmaceutical ingredients (API) is a major
      challenge in drug development impairing bioavailability and therapeutic benefit.
      This study is addressing the possibility to tailor pharmaceutical and physical
      properties of APIs by transforming these into tetrabutylphosphonium (TBP) salts,
      including the generation of ionic liquids (IL). Therefore, poorly water soluble
      acidic APIs (Diclofenac, Ibuprofen, Ketoprofen, Naproxen, Sulfadiazine,
      Sulfamethoxazole, and Tolbutamide) were converted into TBP ILs or low melting
      salts and compared to the corresponding sodium salts. Free acids and TBP salts
      were characterized by NMR and IR spectroscopy, DSC and XRPD, DVS and dissolution
      rate measurements, release profiles, and saturation concentration measurements.
      TBP salts had lower melting points and glass transition temperatures and
      dissolution rates were improved up to a factor of 1000 as compared to the
      corresponding free acid. An increase in dissolution rates was at the expense of
      increased hygroscopicity. In conclusion, the creation of TBP ionic liquids or
      solid salts from APIs is a valuable concept addressing dissolution and solubility
      challenges of poorly water soluble acidic compounds. The data suggested that
      tailor-made counterions may substantially expand the formulation scientist's
      armamentarium to meet challenges of poorly water soluble drugs. 

PMID- 25976316
TI  - Development of orodispersible polymer films with focus on the solid state
      characterization of crystalline loperamide.
AB  - The formulation of active pharmaceutical ingredients (API) as orodispersible
      films is gaining interest among novel oral drug delivery systems due to their
      small size, enhanced flexibility and improved patient compliance. The aim of this
      work was the preparation and characterization of orodispersible films containing
      loperamide hydrochloride (LPH) as model drug. As loperamide hydrochloride is
      poorly soluble in water it was used in crystalline form with a loading of
      2mg/6cm(2) film. Hydroxypropyl methylcellulose (HPMC) and different types of
      hydroxypropyl cellulose (HPC) in different concentrations were used as film
      forming polymers whereas arabic gum, xanthan gum and tragacanth served as
      thickening agents. Films were characterized with respect to the content
      uniformity, morphology, thermal behavior and crystallinity. Suspensions were
      investigated regarding their viscosity using a rotational rheometer and the
      crystal structure of the Active Pharmaceutical Ingredient (API) was analyzed
      using polarized light microscopy. The development of flexible, non-brittle and
      homogeneous films of LPH was feasible. Two polymorphic forms of LPH appeared in
      the film formulations dependent on the utilized polymer. While in presence of
      HPMC the original polymorphic form I remained stable in suspension and films, the
      polymorphic form II occurred in presence of HPC. Both polymorphic forms were
      prepared separately and a solid state characterization was performed. Polymorph I
      showed isometric crystals whereas polymorph II showed needle shaped crystals.
      Tragacanth was able to prevent the transformation to polymorph II, if it was
      dissolved first before HPC. When HPC was added first to the suspension, the
      conversion to form II occurred irreversibly also after further addition of
      tragacanth. 

PMID- 25976320
TI  - The politics of invisibility: public knowledge about radiation health effects
      after Chernobyl.

PMID- 25976318
TI  - High density lipoprotein promotes proliferation of adipose-derived stem cells via
      S1P1 receptor and Akt, ERK1/2 signal pathways.
AB  - INTRODUCTION: Adipose-derived stem cells (ADSC) are non-hematopoietic mesenchymal
      stem cells that have shown great promise in their ability to differentiate into
      multiple cell lineages. Their ubiquitous nature and the ease of harvesting have
      attracted the attention of many researchers, and they pose as an ideal candidate
      for applications in regenerative medicine. Several reports have demonstrated that
      transplanting ADSC can promote repair of injured tissue and angiogenesis in
      animal models. Survival of these cells after transplant remains a key limiting
      factor for the success of ADSC transplantation. Circulating factors like High
      Density Lipoprotein (HDL) has been known to promote survival of other stems cells
      like bone marrow derived stem cells and endothelial progenitor cells, both by
      proliferation and by inhibiting cell apoptosis. The effect of HDL on transplanted
      adipose-derived stem cells in vivo is largely unknown. METHODS: This study
      focused on exploring the effects of plasma HDL on ADSC and delineating the
      mechanisms involved in their proliferation after entering the bloodstream. Using
      the MTT and BrdU assays, we tested the effects of HDL on ADSC proliferation. We
      probed the downstream intracellular Akt and ERK1/2 signaling pathways and
      expression of cyclin proteins in ADSC using western blot. RESULTS: Our study
      found that HDL promotes proliferation of ADSC, by binding to sphingosine-1-
      phosphate receptor-1(S1P1) on the cell membrane. This interaction led to
      activation of intracellular Akt and ERK1/2 signaling pathways, resulting in
      increased expression of cyclin D1 and cyclin E, and simultaneous reduction in
      expression of cyclin-dependent kinase inhibitors p21 and p27, therefore promoting
      cell cycle progression and cell proliferation. CONCLUSIONS: These studies raise
      the possibility that HDL may be a physiologic regulator of stem cells and
      increasing HDL concentrations may be valuable strategy to promote ADSC
      transplantation.

PMID- 25976319
TI  - Immunological and molecular characterization of Leptospira interrogans isolated
      from a bovine foetus.
AB  - Cattle are commonly infected with pathogenic leptospires, and similarly to
      rodents, they excrete the bacteria in their urine and can transmit the pathogen
      from animal to animal or animal to human. Thus, surveillance and monitoring
      systems for detection of new Leptospira serovars are important for the control of
      leptospirosis. Here, we report the isolation of a spirochete from a stillborn
      bovine foetus and its characterization by immunological and molecular techniques.
      A variable number tandem repeat profile using seven discriminatory primers
      identified the spirochete as belonging to species Leptospira interrogans
      serogroup Australis serovar Muenchen. A phenotypic analysis using monoclonal
      antibodies (mAbs) against leptospiral membrane-associated proteins confirmed the
      expression of important virulence and pathogenicity factors (LipL32 and LigBrep).
      Out of 120 reference sera tested, 22 positive (36.66%) and 9 negative (15%) also
      reacted with the new isolate. Furthermore, the serovar Muenchen isolate was
      virulent in hamster model. The animal inoculated developed acute lethal infection
      characterized by hepatic, pulmonary and renal lesions. Local isolates exhibited
      unique characteristics that differed from those of reference strains; therefore,
      isolation of leptospires is useful in the surveillance of local pathogenic
      serovars. In conclusion, the data obtained from this study can contribute to the
      epidemiological understanding and control of leptospirosis in southern Brazil. 

PMID- 25976321
TI  - The multi-facets of sustainable nanotechnology - Lessons from a nanosafety
      symposium.
AB  - An international symposium for nanosafety was held recently at the Nanyang
      Technological University in Singapore. Topics relating to understanding
      nanomaterial properties, tools, and infrastructure required for predicting
      hazardous outcomes, measuring nanomaterial exposure levels, systems approach for
      risk assessment and public's perception of nanotechnology were covered. The need
      for a multidisciplinary approach, across both natural and social sciences, for
      developing sustainable nanotechnology solutions was heavily emphasized. This
      commentary highlights the major issues discussed and the commitment of the
      nanosafety research community in Singapore to contribute collectively to realise
      the vision of sustainable nanotechnology. 

PMID- 25976323
TI  - Assembly of the secretion pores GspD, Wza and CsgG into bacterial outer membranes
      does not require the Omp85 proteins BamA or TamA.
AB  - In Gram-negative bacteria, beta-barrel proteins are integrated into the outer
      membrane by the beta-barrel assembly machinery, with key components of the
      machinery being the Omp85 family members BamA and TamA. Recent crystal structures
      and cryo-electron microscopy show a diverse set of secretion pores in Gram
      negative bacteria, with alpha-helix (Wza and GspD) or beta-strand (CsgG)
      transmembrane segments in the outer membrane. We developed assays to measure the
      assembly of three distinct secretion pores that mediate protein (GspD), curli
      fibre (CsgG) and capsular polysaccharide (Wza) secretion by bacteria and show
      that depletion of BamA and TamA does not diminish the assembly of Wza, GspD or
      CsgG. Like the well characterised pilotins for GspD and other secretins, small
      periplasmic proteins enhance the assembly of the CsgG beta-barrel. We discuss a
      model for integral protein assembly into the bacterial outer membrane, focusing
      on the commonalities and differences in the assembly of Wza, GspD and CsgG. 

PMID- 25976322
TI  - Association of childhood trauma with fatigue, depression, stress, and
      inflammation in breast cancer patients undergoing radiotherapy.
AB  - BACKGROUND: This pilot study examined whether breast cancer patients with
      childhood trauma exhibit increased fatigue, depression, and stress in association
      with inflammation as a result of whole breast radiotherapy (RT). METHODS: Twenty
      breast cancer patients were enrolled in a prospective, longitudinal study of
      fatigue, depression, and perceived stress prior to RT, week 6 of RT, and 6 weeks
      post-RT. Six weeks after RT, subjects completed the childhood trauma
      questionnaire (CTQ). Patients were also administered the multidimensional fatigue
      inventory, inventory of depressive symptomatology-self-reported, and perceived
      stress scale at all three time-points and underwent blood sampling prior to RT
      for gene expression and inflammatory markers previously associated with childhood
      trauma and behavioral symptoms in breast cancer patients. RESULTS: Eight subjects
      (40%) had past childhood trauma (CTQ+). Compared to CTQ- patients, CTQ+ patients
      had significantly higher fatigue, depression, and stress scores before, during,
      and after RT (p < 0.05); however, RT did not increase these symptoms in either
      group. CTQ+ patients also exhibited increased baseline expression of gene
      transcripts related to inflammatory signaling, and baseline inflammatory markers
      including c-reactive protein, interleukin (IL)-6, and IL-1 receptor antagonist
      were positively correlated with depression, fatigue, and stress scores in CTQ+
      but not CTQ- patients. CONCLUSIONS: Childhood trauma was prevalent and was
      associated with increased symptoms of fatigue, depression, and stress
      irrespective of RT. Increased symptoms in CTQ+ patients were also associated with
      baseline inflammatory markers. Treatments targeting childhood trauma and related
      inflammation may improve symptoms in breast cancer patients.

PMID- 25976324
TI  - The use of human amniotic fluid stem cells as an adjunct to promote pulmonary
      development in a rabbit model for congenital diaphragmatic hernia.
AB  - OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal
      injection of human amniotic fluid stem cells (hAFSC) on pulmonary development
      combined with TO in a rabbit model for CDH. METHODS: In time-mated pregnant does
      a left diaphragmatic defect was created at d23 (term = 31). At d28, previously
      operated fetuses were assigned to either TO and injection with 70 MUL of
      phosphate buffered saline (PBS) or 1.0 * 10(6) c-Kit positive hAFSC expressing
      LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their
      lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal
      staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B).
      RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses
      LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The
      additional injection of hAFSC decreases MTBD and results in a non-significant
      decrease in muscularization of intra-acinary vessels. There were no inflammatory
      changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4
      days after injection. CONCLUSION: HAFSC exert an additional effect on TO leading
      to a decrease in MTBD, a measure of alveolar number surrounding the terminal
      bronchioles, without signs of toxicity. (c) 2015 John Wiley & Sons, Ltd.

PMID- 25976326
TI  - Modern climate and vegetation variability recorded in organic compounds and
      carbon isotopic compositions in the Dianchi watershed.
AB  - The aliphatic hydrocarbons distribution and compound-specific characteristics of
      carbon isotopic compositions in the sediments from the small catchment (197
      km(2)) of the Dianchi watershed were investigated for identification of modern
      climate and vegetation variations in the study area. Results show that a regular
      bimodal n-alkanes distribution ranged from nC16 to nC33, with strong dominance at
      nC17 for short-chain n-alkanes and nC31 for long-chain n-alkanes. Mass
      chromatogram of total fatty acids also indicates corresponding mixed contribution
      of algae, hydrophilous non-emergent (C4 plants) and terrestrial plants (C3
      plants) to sedimentary organic matter (OM). At the depth of -24 to -25 cm (early
      1970s), nC31/nC17 and terrestrial to aquatic ratio of hydrocarbons (TAR) values
      decrease, suggesting a shift of OM origins from C3 terrestrial plants to algae
      derived C4 plants. The highest water stage in 1971 was found to be recorded in
      the particle size (<4 MUm). For long-chain alkanes, the values of delta (13)Corg
      and delta (13)Cn-alkanes varied from -26.9 to -22.4 and -33.4 to -27.9 0/00,
      respectively. Population growth and economic development led to a demand for
      abundant habitable and cultivable land. Due to unreasonable land expansion, the
      primordial forest sporadically distributed. A mixture of C3 and C4 plants
      probably replaced C3 plants as the sources of OM in the past 10 years. The
      changes of land-use types and severe drought resulted in the excessive OM inputs
      to the watershed.

PMID- 25976325
TI  - Emergence and potential for spread of Chikungunya virus in Brazil.
AB  - BACKGROUND: In December 2013, an outbreak of Chikungunya virus (CHIKV) caused by
      the Asian genotype was notified in the Caribbean. The outbreak has since spread
      to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV
      infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana,
      Northeast Brazil. METHODS: We compiled epidemiological and clinical data on
      suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic
      was conducted on 68 serum samples from patients with symptom onset between April
      and September 2014. Two imported and four autochthonous cases were selected for
      virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic
      analysis. We then followed CDC/PAHO guidelines to estimate the risk of
      establishment of CHIKV in Brazilian municipalities. RESULTS: We detected 41 CHIKV
      importations and 27 autochthonous cases in Brazil. Epidemiological and
      phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in
      Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating
      in Feira de Santana. The presumed index case of the ECSA genotype was an
      individual who had recently returned from Angola and developed symptoms in Feira
      de Santana. We estimate that, if CHIKV becomes established in Brazil,
      transmission could occur in 94% of municipalities in the country and provide maps
      of the risk of importation of each strain of CHIKV in Brazil. CONCLUSIONS: The
      etiological strains associated with the early-phase CHIKV outbreaks in Brazil
      belong to the Asian and ECSA genotypes. Continued surveillance and vector
      mitigation strategies are needed to reduce the future public health impact of
      CHIKV in the Americas.

PMID- 25976327
TI  - Effects of algal bloom formation, outbreak, and extinction on heavy metal
      fractionation in the surficial sediments of Chaohu Lake.
AB  - The effects of algal bloom (AB) on the physicochemical and biochemical properties
      of water and sediment in lakes have been widely studied. However, limited
      attention has been directed toward the effects of the processes of AB formation,
      outbreak, and extinction on heavy metal fractionation in sediment. In this study,
      water and sediment samples were collected from the AB and free algal bloom (FAB)
      regions of Chaohu Lake from May to September in 2012. The chemical fractionation
      of seven heavy metals (Cd, Cr, Cu, Mn, Ni, Fe, and Pb) in sediment was determined
      by using a modified three-step sequential procedure. Evident processes of AB
      formation, outbreak, and extinction were observed in the AB region, but not in
      the FAB region. The TN and TP concentrations in water and sediment in the AB
      region were significantly higher than those in the FAB region. The water DO
      concentration was higher in the AB region than that in the FAB region before the
      early stage of the AB outbreak, but an opposite trend was observed in the stages
      that followed. Metal fractionation in sediment showed that except for Mn and Cu,
      the majority of metals were in the residual fraction regardless of the AB
      process. The AB process slightly altered the concentrations of metal fractions,
      except for reducible Fe and oxidizable Cu. The result showed that AB formation,
      outbreak, and extinction slightly affected heavy metal fractionation in sediment
      though water properties were significantly different among AB processes. 

PMID- 25976328
TI  - Effects of fluoranthene on the fitness-related traits and antioxidative defense
      in Lymantria dispar L.
AB  - This study aimed to examine the effects of ubiquitous polycyclic aromatic
      hydrocarbon fluoranthene, supplemented to an artificial diet, on the fitness
      related traits and activity of midgut antioxidative enzymes-superoxide dismutase
      (SOD) and catalase (CAT), and expression of their isoforms in the fifth-instar
      gypsy moth Lymantria dispar L. Prolonged duration of development and reduced
      weight and relative growth rate were recorded in larvae reared on the diets
      supplemented with different concentrations of fluoranthene. SOD and CAT
      activities were significantly higher in the midguts of fluoranthene-treated
      larvae, compared to that of the control group. Different expression patterns were
      detected for SOD as well as for CAT isoforms, depending on the supplemented
      concentration of fluoranthene. Obtained results suggest that the activity of
      these enzymes in gypsy moth larvae may be used as biomarkers for assessing
      pollution, even at low concentrations of the pollutant. 

PMID- 25976329
TI  - The influence of Ce doping of titania on the photodegradation of phenol.
AB  - Pure and cerium-doped [0.05, 0.1, 0.3, 0.5, and 1.0 Ce nominal atomic % (at.%)]
      TiO2 was synthesized by the sol-gel method. The obtained catalysts were
      characterized by X-ray diffraction (XRD), UV-visible diffused reflectance
      spectroscopy (DRS), Raman, and BET surface area measurement. The photocatalytic
      activity of synthesized samples for the oxidative degradation of phenol in
      aqueous suspension was investigated. The content of Ce in the catalysts increases
      both the transition temperature for anatase to rutile phase transformation and
      the specific surface area, and decreases the crystallite size of anatase phase,
      the crystallinity, and the band gap energy value. The material with higher
      efficiency corresponds to 0.1 Ce nominal at.%. Under irradiation with 350 nm
      lamps, the degradation of phenol could be described as an exponential trend, with
      an apparent rate constant of (9.1 +/- 0.6) 10(-3) s(-1) (r(2) = 0.98).
      Hydroquinone was identified as the main intermediate.

PMID- 25976330
TI  - Evaluation of the behavior of clouds in a region of severe acid rain pollution in
      southern China: species, complexes, and variations.
AB  - Cloud samples were collected during the summer of 2011 and the spring of 2012 at
      a high-elevation site in southern China in an effort to examine the chemical
      characteristics of acid clouds. In total, 141 cloud samples were collected during
      44 cloud events over the observation period. The dominant ionic species were
      SO4(2-), NH4(+), and NO3(-), contributing approximately 75% of the total
      inorganic ion concentration. The primary acidifying factors were sulfate and
      nitrate, and the primary neutralizing factors were ammonium and calcium. The
      volume-weighted mean (VWM) pH of the cloud water was 3.79, indicating an acidic
      nature. In these cloud samples, Zn and Al exhibited the highest trace metal
      concentrations, contributing approximately 60% of the total trace element
      concentration. Toxic metals, such as Pb, Ba, As, and Cr, were detected at high
      concentrations, indicating potential hazards for human health, vegetation, and
      waters in this region. Visual MINTEQ 3.0 results revealed that the majority of
      Zn(II) and Pb(II) existed in the form of free ions. The behavior of Al, however,
      differed from the behaviors of zinc and lead. The temporal variation in cloud
      chemistry indicated that temperature, sandstorms, and long-range transport could
      affect the concentrations of species. During the lifetime of a cloud event, the
      concentrations of the chemical species were controlled by the transfer of gases
      or particles to liquid droplets.

PMID- 25976331
TI  - Catalytic hydrodechlorination of monochloroacetic acid in wastewater using Ni-Fe
      bimetal prepared by ball milling.
AB  - Monochloroacetic acid (MCA) is a chemically stable and biologically toxic
      pollutant. It is often generated during the production of the pesticide
      dimethoate. Conventional wastewater treatment processes have difficulty degrading
      it. In this work, the dechlorination effects of Ni-Fe bimetal prepared using ball
      milling (BM) technology for the high concentrations of MCA in wastewater were
      examined. The MCA in aqueous solution was found to be degraded efficiently by the
      Ni-Fe bimetal. However, S-(methoxycarbonyl) methyl O, O-dimethyl
      phosphorodithioate (SMOPD) in wastewater, a by-product of the dimethoate
      production process, significantly inhibited the reductive dechlorination activity
      of Ni-Fe bimetal. Increasing the reaction temperature in the MCA wastewater
      enhanced the reduction activity of the Ni-Fe bimetal effectively. Oxygen was
      found to be unfavorable to dechlorination. Sealing the reaction to prevent
      oxidation was found to render the degradation process more efficient. The process
      retained over 88% efficiency after 10 treatment cycles with 50 g/L of Ni-Fe
      bimetal under field conditions.

PMID- 25976332
TI  - The effectiveness of various treatments in changing the nutrient status and
      bioavailability of risk elements in multi-element contaminated soil.
AB  - Potential changes in the mobility and bioavailability of risk and essential macro
      and micro-elements achieved by adding various ameliorative materials were
      evaluated in a model pot experiment. Spring wheat (Triticum aestivum L.) was
      cultivated under controlled condition for 60 days in two soils, uncontaminated
      Chernozem and multi-element contaminated Fluvisol containing 4900 +/- 200 mg/kg
      Zn, 35.4 +/- 3.6 mg/kg Cd, and 3035 +/- 26 mg/kg Pb. The treatments were all
      contained the same amount of sulfur and were as follows: (i) digestate from the
      anaerobic fermentation of biowaste, (ii) fly ash from wood chip combustion, and
      (iii) ammonium sulfate. Macro- and micro-nutrients Ca, Mg, K, Fe, Mn, Cu, P, and
      S, and risk elements Cd, Cr, Pb, and Zn were assayed in soil extracts with 0.11
      mol/l solution of CH3COOH and in roots, shoots, and grain of wheat after 30 and
      60 days of cultivation. Both digestate and fly ash increased levels of macro- and
      micro-nutrients as well as risk elements (especially Cd and Zn; the mobility of
      Pb decreased after 30 days of cultivation). The changes in element mobility in
      ammonium sulfate-treated soils appear to be due to both changes in soil pH level
      and inter-element interactions. Ammonium sulfate tended to be the most effective
      measure for increasing nutrient uptake by plants in Chernozem but with opposite
      pattern in Fluvisol. Changes in plant yield and element uptake in treated plants
      may have been associated with the higher proline content of wheat shoots
      cultivated in both soils compared to control. None of the treatments decreased
      uptake of risk elements by wheat plants in the extremely contaminated Fluvisol,
      and their accumulation in wheat grains significantly exceeded maximum permissible
      levels; these treatments cannot be used to enable cereal and other crop
      production in such soils. However, the combination of increased plant growth
      alongside unchanged element content in plant biomass in pots treated with
      digestate and fly ash suggests that these treatments have a beneficial impact on
      yield and may be effective treatments in crops grown for phytoremediation. 

PMID- 25976333
TI  - An evaluation of organic substance fraction removal during ion exchange with Miex
      DOC resin.
AB  - In this study, the usefulness of Miex-DOC resin in eliminating organic substances
      and their fractions from water sources for drinking water was evaluated. The
      objects of study were samples from three surface water sources and one
      infiltration water source taken at water treatment plants before treatment in
      technical conditions. In particular, the effectiveness of removing biodegradable
      and non-biodegradable fractions as a function of resin dosages and water-resin
      contact times was evaluated. The ion exchange process with the Miex-DOC resin
      achieved a high effectiveness in removing aromatic non-biodegradable organic
      substances, and therefore a reduction in UV254 absorbance. The biodegradable
      fraction is much less susceptible to removal yet its removal effectiveness allows
      for a significant reduction in hazards connected with secondary microorganism
      development. The results of this study indicate the possibility of using ion
      exchange with the Miex-DOC resin for effective removal of disinfection by-product
      precursors. 

PMID- 25976334
TI  - Combining UV-C treatment with biocontrol yeast to control postharvest decay of
      melon.
AB  - Significant losses in harvested melon can be directly attributable to decay
      fungi. In the present study, the use of UV-C treatment combined with biocontrol
      yeast, Pichia cecembensis, was evaluated for their ability to control postharvest
      decay of melon fruits after they were artificially inoculated with Fusarium
      oxysporum and Alternaria alternata. Natural infection of fruit was also assessed.
      As a stand-alone treatment, UV-C or P. cecembensis significantly reduced Fusarium
      rot and Alternaria rot, and also the level of natural infection on melon fruit,
      relative to the untreated control. The combination of UV-C or P. cecembensis,
      however, provided a superior level of decay control on artificially inoculated
      and naturally infected fruit, compared to either treatment alone. None of the
      treatments impaired fruit quality. Integrating the use of UV-C treatment with
      biocontrol yeast has potential as an effective method to control postharvest
      decay of melon. 

PMID- 25976335
TI  - Steady shearing flows of deformable, inelastic spheres.
AB  - We extend models for granular flows based on the kinetic theory beyond the
      critical volume fraction at which a rate-independent contribution to the stresses
      develops. This involves the incorporation of a measure of the duration of the
      particle interaction before and after this volume fraction. At volume fractions
      less than the critical, the stress components contain contributions from momentum
      exchanged in collisions that are influenced by the particle elasticity. At volume
      fractions greater than the critical, the stress components contain both static
      contributions from particle elasticity and dynamic contributions from the
      momentum transfer associated with the release of elastic energy by the breaking
      of force chains. A simple expression for the duration of a collision before and
      after the critical volume fraction permits a smooth transition between the two
      regimes and predictions for the components of the stress in steady, homogeneous
      shearing that are in good agreement with the results of numerical simulations.
      Application of the theory to steady, inhomogeneous flows reproduces the features
      of such flows seen in numerical simulations and physical experiments. 

PMID- 25976336
TI  - Rapamycin enhanced the antitumor efficacy of oxaliplatin in cisplatin-resistant
      ovarian cancer cells A2780cis both in vitro and in vivo.
AB  - OBJECTIVE: This study aimed to investigate the efficacy of combination of
      rapamycin, an mammalian target of rapamycin (mTOR) inhibitor for treating
      rejection after organ transplantation, and oxaliplatin, a third-generation of
      platinum drug usually used to treat chemoresistant or progressive ovarian cancer,
      in cisplatin-resistant ovarian carcinoma cells A2780cis. METHODS/MATERIALS:
      Expressions of mTOR and its target molecules p70S6K and 4E-BP1 were determined in
      cisplatin-sensitive and -resistant cells A2780 and A2780cis, respectively, using
      Western blotting. Proliferation of A2780cis exposure to oxaliplatin or
      oxaliplatin plus rapamycin was examined using MTT assay in vitro as well as a
      nude mice model in vivo. Cell apoptosis and proapoptosis proteins including
      caspase-8 and -3 and PARP were determined using flow cytometry and Western
      blotting. RESULTS: We found that A2780cis cells had partial cross-resistance
      between cisplatin and oxaliplatin. The levels of phosphorylated mTOR (p-mTOR),
      p70S6K, and 4E-BP1 were significantly increased in A2780cis cells compared to
      A2780 cells, which might be implicated in cisplatin-induced chemoresistance.
      Rapamycin obviously enhanced the inhibitory effect of oxaliplatin on the growth
      of A2780cis both in vitro and in vivo. Rapamycin slightly induced cell apoptosis
      but significantly enhanced the effect of oxaliplatin in soliciting apoptosis of
      A2780cis cells, which might be ascribed to its ability in further increasing the
      levels of cleaved caspase-8 and -3 and PARP induced by oxaliplatin. CONCLUSION:
      These results suggested that combination of oxaliplatin and rapamycin enhanced
      the antitumour efficacy of oxaliplatin in A2780cis cells and therefore might have
      a role in treating cisplatin-resistant ovarian carcinoma.

PMID- 25976337
TI  - Examining Postoperative Outcomes after Employing a Surgical Algorithm for
      Management of Peyronie's Disease: A Single-Institution Retrospective Review.
AB  - AIM: Surgery remains the gold standard treatment for men with stable Peyronie's
      disease (PD). In an attempt to guide operative selection, we report our series of
      penile-straightening procedures for PD, using a surgical algorithm that
      recommended tunica albuginea plication (TAP), partial plaque excision and
      grafting (PEG) or inflatable penile prosthesis (IPP) placement. With this study,
      we attempt to further refine surgical approach, define realistic surgical
      outcomes, and help establish reasonable postoperative expectations for treatment
      of PD. METHODS: We retrospectively reviewed all patients who underwent surgery
      for PD at our institution between 2007 and 2013. Work-up involved a history,
      physical exam, and a duplex ultrasound. Several questionnaires were employed to
      assess bother and distress associated with PD. Objective outcomes and patient
      satisfaction were assessed postoperatively. Primary outcomes include
      postoperative patient satisfaction with rigidity, curvature, and ability to
      engage in intercourse. Secondary outcomes include comparing emotional,
      relationship, and psychological distress to severity of disease. RESULTS: A total
      of 390 patients underwent penile-straightening procedures for correction of PD.
      Of these patients, 29%, (n = 114) underwent TAP, 41% (n = 159) PEG, and 30% (N =
      114) IPP. Mean follow-up was 17 months. The three surgical modalities showed no
      significant difference in satisfaction with penile rigidity, presence of
      bothersome residual curve, or ability to engage in intercourse. Preoperatively,
      80% of men reported a negative effect of PD on their emotional status.
      Postoperatively, 88.4% of men were able to engage in penetrative intercourse,
      while only 70% were satisfied with rigidity and 84.9% were satisfied with
      curvature correction. CONCLUSION: Patient experience with postsurgical rigidity,
      ability to engage in intercourse, and residual bothersome curve was not
      statistically different across the three groups, supporting the use of this
      surgical algorithm. The majority of patients with PD experience some degree of
      emotional and psychological distress, which may compromise patient satisfaction.

PMID- 25976338
TI  - Musculoskeletal pain in schoolchildren across puberty: a 3-year follow-up study.
AB  - BACKGROUND: Chronic Musculoskeletal Pain (MSP) in children can be due to non
      inflammatory conditions, such as the benign joint hypermobility syndrome (BJHS)
      or idiopathic MSP (IMSP). Aim of the study was to evaluate type and persistence
      of MSP in a cohort of schoolchildren with MSP followed for 3 years, in order to
      identify the main risk factors. METHODS: Healthy schoolchildren, aged 8-13 years,
      underwent a general and rheumatologic examination, focusing on presence of
      chronic MSP, defined as continuous or recurrent pain lasting more than 3 months
      and heavily interfering with daily life activities, presence of generalized joint
      hypermobility, the body mass index and the pubertal stage. All symptomatic
      subjects were re-evaluated 3 years later with the same methods. RESULTS: Seventy
      of the 88 symptomatic subjects of the initial cohort of 289 were re-evaluated 3
      years later. Of these, 38 (54.3 %) still presented MSP, including 19 with BJHS
      and 19 with IMSP. Main symptoms were lower limbs arthralgia and myalgia. MSP
      persisted more in females than in males (p = 0.038) and in pubertal rather than
      pre-pubertal subjects (p = 0.022); these subjects recovered significantly more
      both from BJHS (p = 0.004) and IMSP (p = 0.016). Gender did not influence the
      distribution of MSP according to pubertal stage. CONCLUSIONS: Female gender, BJHS
      and pubertal stage are important risk factors for persistence of MSP. Further
      studies are needed to evaluate the natural history of MSP towards adulthood and
      the role of the pubertal age.

PMID- 25976339
TI  - Primary pineal malignant melanoma with B-Raf V600E mutation: a case report and
      brief review of the literature.
AB  - Primary pineal melanoma is exceedingly rare, and sufficient treatment options
      have not been established. Here we describe a 57-year-old male patient who
      presented with short-term memory disturbance and ataxia. Magnetic resonance
      imaging of the brain showed a tumor mass in the pineal gland. Biopsy revealed a
      malignant melanocytic tumor. No primary malignant melanoma was known, and
      extensive imaging studies including PET-CT excluded other sites affected by a
      malignant melanoma. The demonstration of the BRAF V600E mutation in the pineal
      tumor made the patient eligible for intrathecal treatment with vemurafenib.
      Unfortunately, the patient died 26 days after surgery due to tumor hemorrhage.
      This is the first report of V600E in primary pineal melanoma, suggesting that a
      fraction of these rare tumors might additionally benefit from vemurafenib
      treatment.

PMID- 25976340
TI  - Decompressive surgery in a patient with hyperostosis corticalis generalisata for
      relief of cognitive disability and dysaesthesia.
AB  - A 28-year-old man with genetically confirmed hyperostosis corticalis generalisata
      (Van Buchem disease) suffered from headache and progressive cognitive and
      sensibility disorders. Bone formation of the skull was ongoing, leading to
      narrowing of the intracranial space and foramen magnum. A large bilateral
      frontoparietal craniotomy and decompression of the foramen magnum resulted in
      almost complete relief of his symptoms. This is the first report on successful
      decompressive surgery as a treatment of cognitive impairment and dysaesthesia. 

PMID- 25976341
TI  - Serum Levels of Nimodipine in Enteral and Parenteral Administration in Patients
      with Aneurysmal Subarachnoid Hemorrhage.

PMID- 25976343
TI  - EuroTag rugby league: a semi-contact version of the game.

PMID- 25976342
TI  - Identification of RNAIII-binding proteins in Staphylococcus aureus using tethered
      RNAs and streptavidin aptamers based pull-down assay.
AB  - BACKGROUND: It has been widely recognized that small RNAs (sRNAs) play important
      roles in physiology and virulence control in bacteria. In Staphylococcus aureus,
      many sRNAs have been identified and some of them have been functionally studied.
      Since it is difficult to identify RNA-binding proteins (RBPs), very little has
      been known about the RBPs in S. aureus, especially those associated with sRNAs.
      RESULTS: Here we adopted a tRNA scaffold streptavidin aptamer based pull-down
      assay to identify RBPs in S. aureus. The tethered RNA was successfully captured
      by the streptavidin magnetic beads, and proteins binding to RNAIII were isolated
      and analyzed by mass spectrometry. We have identified 81 proteins, and expressed
      heterologously 9 of them in Escherichia coli. The binding ability of the
      recombinant proteins with RNAIII was further analyzed by electrophoresis mobility
      shift assay, and the result indicates that proteins CshA, RNase J2, Era, Hu,
      WalR, Pyk, and FtsZ can bind to RNAIII. CONCLUSIONS: This study suggests that
      some proteins can bind to RNA III in S. aureus, and may be involved in RNA III
      function. And tRSA based pull-down assay is an effective method to search for
      RBPs in bacteria, which should facilitate the identification and functional study
      of RBPs in diverse bacterial species.

PMID- 25976344
TI  - Neurological morphofunctional differentiation induced by REAC technology in PC12.
      A neuro protective model for Parkinson's disease.
AB  - Research for the use of physical means, in order to induce cell differentiation
      for new therapeutic strategies, is one of the most interesting challenges in the
      field of regenerative medicine, and then in the treatment of neurodegenerative
      diseases, Parkinson's disease (PD) included. The aim of this work is to verify
      the effect of the radio electric asymmetric conveyer (REAC) technology on the
      PC12 rat adrenal pheochromocytoma cell line, as they display metabolic features
      of PD. PC12 cells were cultured with a REAC regenerative tissue optimization
      treatment (TO-RGN) for a period ranging between 24 and 192 hours. Gene expression
      analysis of specific neurogenic genes, as neurogenin-1, beta3-tubulin and Nerve
      growth factor, together with the immunostaining analysis of the specific neuronal
      protein beta3-tubulin and tyrosine hydroxylase, shows that the number of cells
      committed toward the neurogenic phenotype was significantly higher in REAC
      treated cultures, as compared to control untreated cells. Moreover, MTT and
      Trypan blue proliferation assays highlighted that cell proliferation was
      significantly reduced in REAC TO-RGN treated cells. These results open new
      perspectives in neurodegenerative diseases treatment, particularly in PD. Further
      studies will be needed to better address the therapeutic potential of the REAC
      technology. 

PMID- 25976346
TI  - Phylodiversity to inform conservation policy: An Australian example.
AB  - Phylodiversity measures summarise the phylogenetic diversity patterns of groups
      of organisms. By using branches of the tree of life, rather than its tips (e.g.,
      species), phylodiversity measures provide important additional information about
      biodiversity that can improve conservation policy and outcomes. As a biodiverse
      nation with a strong legislative and policy framework, Australia provides an
      opportunity to use phylogenetic information to inform conservation decision
      making. We explored the application of phylodiversity measures across Australia
      with a focus on two highly biodiverse regions, the south west of Western
      Australia (SWWA) and the South East Queensland bioregion (SEQ). We analysed seven
      diverse groups of organisms spanning five separate phyla on the evolutionary tree
      of life, the plant genera Acacia and Daviesia, mammals, hylid frogs, myobatrachid
      frogs, passerine birds, and camaenid land snails. We measured species richness,
      weighted species endemism (WE) and two phylodiversity measures, phylogenetic
      diversity (PD) and phylogenetic endemism (PE), as well as their respective
      complementarity scores (a measure of gains and losses) at 20 km resolution.
      Higher PD was identified within SEQ for all fauna groups, whereas more PD was
      found in SWWA for both plant groups. PD and PD complementarity were strongly
      correlated with species richness and species complementarity for most groups but
      less so for plants. PD and PE were found to complement traditional species-based
      measures for all groups studied: PD and PE follow similar spatial patterns to
      richness and WE, but highlighted different areas that would not be identified by
      conventional species-based biodiversity analyses alone. The application of
      phylodiversity measures, particularly the novel weighted complementary measures
      considered here, in conservation can enhance protection of the evolutionary
      history that contributes to present day biodiversity values of areas.
      Phylogenetic measures in conservation can include important elements of
      biodiversity in conservation planning, such as evolutionary potential and feature
      diversity that will improve decision-making and lead to better biodiversity
      conservation outcomes.

PMID- 25976345
TI  - Effect of common neuropathologies on progression of late life cognitive
      impairment.
AB  - Brain pathologies of Alzheimer's (AD), cerebrovascular, and Lewy body diseases
      are common in old age, but the relationship of these pathologies with progression
      from normal cognitive function to the various stages of cognitive impairment is
      unknown. In this study, we fit latent Markov models from longitudinal cognitive
      data to empirically derive 3 latent stages corresponding to no impairment, mild
      impairment, and moderate impairment; then, we examined the associations of common
      neuropathologies with the rates of transition among these stages. Cognitive and
      neuropathological data were available from 653 autopsied participants in 2
      ongoing cohort studies of aging who were cognitively healthy at baseline (mean
      baseline age 79.1 years) and had longitudinal cognitive data. On average,
      participants in these analyses developed mild impairment 5 years after
      enrollment, progressed to moderate impairment after an additional 3.4 years, and
      stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts
      were associated with a higher risk of progression to mild impairment and
      subsequently to moderate impairment. By contrast, Lewy bodies were associated
      only with progression from mild to moderate impairment. The 5-year probability of
      progression to mild or moderate impairment was 20% for persons without any of
      these 3 pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and
      56% for AD, infarcts, and Lewy bodies. Thus, the presence of AD pathology alone
      nearly doubles the risk of developing cognitive impairment in late life, and the
      presence of multiple pathologies further increases this risk over multiple years
      before death.

PMID- 25976347
TI  - Optical coherence tomography and intravascular ultrasound evaluation of cardiac
      allograft vasculopathy with and without intimal neovascularization.
AB  - AIMS: Neovascularization is closely associated with plaque progression in non
      heart transplantation subjects; on the other hand, cardiac allograft vasculopathy
      causes unfavourable outcomes. Intravascular ultrasound (IVUS) and optical
      coherence tomography (OCT) can provide microscopic assessment in vivo. The aim of
      this study was to investigate the impact of neovascularization on intimal
      proliferation. METHODS AND RESULTS: Both IVUS and OCT were attempted in 45
      consecutive patients during annual catheterization after heart transplantation.
      There were 115 vessels [28 vessels were catheterized within 8 weeks of heart
      transplantation (baseline)]. IVUS analysis assessed vessel, luminal, and intimal
      (vessel-lumen) volume using Simpson's method. Qualitative parameters including
      microchannel were assessed by OCT. A microchannel was defined as a no-signal
      tubuloluminal structure with a sharply delineated border considered to represent
      neovascularization. Microchannel was observed more often in patient who had their
      heart transplant more than a year prior to the imaging, compared with shorter
      periods (39.1 vs. 10.7%, P = 0.023). All microchannels were seen in thickness
      >0.5 mm, and intimal volume index (mm(3)/mm) correlated with frequency of
      microchannel (r = 0.54, P = 0.04). The risks for microchannels were donor age
      [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03-1.22; P = 0.007],
      cytomegalovirus infection (OR 16.21; 95% CI 1.79-220.09; P = 0.012), diabetes (OR
      9.5; 95% CI 1.21-116.10; P = 0.032), LDL-cholesterol (OR 1.07; 95% CI 1.01-1.13;
      P = 0.010), and intimal volume (OR 2.47; 95% CI 1.13-6.36; P = 0.023).
      CONCLUSION: OCT-identified microchannels increased sharply within the first year
      and were correlated with intimal volume and coronary risks. This suggests that
      neovascularization may play an important role in the progression of cardiac
      allograft vasculopathy.

PMID- 25976348
TI  - Incidental findings in patients screened for transcatheter aortic valve
      replacement: crystal ball or Pandora's box?

PMID- 25976349
TI  - Investigating the possible effect of electrode support structure on motion
      artifact in wearable bioelectric signal monitoring.
AB  - BACKGROUND: With advances in technology and increasing demand, wearable biosignal
      monitoring is developing and new applications are emerging. One of the main
      challenges facing the widespread use of wearable monitoring systems is the motion
      artifact. The sources of the motion artifact lie in the skin-electrode interface.
      Reducing the motion and deformation at this interface should have positive
      effects on signal quality. In this study, we aim to investigate whether the
      structure supporting the electrode can be designed to reduce the motion artifact
      with the hypothesis that this can be achieved by stabilizing the skin
      deformations around the electrode. METHODS: We compare four textile electrodes
      with different support structure designs: a soft padding larger than the
      electrode area, a soft padding larger than the electrode area with a novel skin
      deformation restricting design, a soft padding the same size as the electrode
      area, and a rigid support the same size as the electrode. With five subjects and
      two electrode locations placed over different kinds of tissue at various mounting
      forces, we simultaneously measured the motion artifact, a motion affected ECG,
      and the real-time skin-electrode impedance during the application of controlled
      motion to the electrodes. RESULTS: The design of the electrode support structure
      has an effect on the generated motion artifact; good design with a skin
      stabilizing structure makes the electrodes physically more motion artifact
      resilient, directly affecting signal quality. Increasing the applied mounting
      force shows a positive effect up to 1,000 gr applied force. The properties of
      tissue under the electrode are an important factor in the generation of the
      motion artifact and the functioning of the electrodes. The relationship of motion
      artifact amplitude to the electrode movement magnitude is seen to be linear for
      smaller movements. For larger movements, the increase of motion generated a
      disproportionally larger artifact. The motion artifact and the induced impedance
      change were caused by the electrode motion and contained the same frequency
      components as the applied electrode motion pattern. CONCLUSION: We found that
      stabilizing the skin around the electrode using an electrode structure that
      manages to successfully distribute the force and movement to an area beyond the
      borders of the electrical contact area reduces the motion artifact when compared
      to structures that are the same size as the electrode area.

PMID- 25976350
TI  - Temperature-Related Reaction Norms of Gene Expression: Regulatory Architecture
      and Functional Implications.
AB  - The environment has profound effects on the expression of many traits and
      reaction norms describe the expression dynamics of a trait across a broad range
      of environmental conditions. Here, we analyze gene expression in Drosophila
      melanogaster across four different developmental temperatures (13-29  degrees C).
      Gene expression is highly plastic with 83.3% of the genes being differentially
      expressed. We distinguished three components of plasticity: 1) Dynamics of gene
      expression intensity (sum of change), 2) direction of change, and 3) curvature of
      the reaction norm (linear vs. quadratic). Studying their regulatory architecture
      we found that all three plasticity components were most strongly affected by the
      number of different transcription factors (TFs) binding to the target gene. More
      TFs were found in genes with less expression changes across temperatures.
      Although the effect of microRNAs was weaker, we consistently noted a trend in the
      opposite direction. The most plastic genes were regulated by fewer TFs and more
      microRNAs than less plastic genes. Different patterns of plasticity were also
      reflected by their functional characterization based on gene ontology. Our
      results suggest that reaction norms provide an important key to understand the
      functional requirements of natural populations exposed to variable environmental
      conditions. 

PMID- 25976351
TI  - Genome-Wide Dosage-Dependent and -Independent Regulation Contributes to Gene
      Expression and Evolutionary Novelty in Plant Polyploids.
AB  - Polyploidy provides evolutionary and morphological novelties in many plants and
      some animals. However, the role of genome dosage and composition in gene
      expression changes remains poorly understood. Here, we generated a series of
      resynthesized Arabidopsis tetraploids that contain 0-4 copies of Arabidopsis
      thaliana and Arabidopsis arenosa genomes and investigated ploidy and hybridity
      effects on gene expression. Allelic expression can be defined as dosage dependent
      (expression levels correlate with genome dosages) or otherwise as dosage
      independent. Here, we show that many dosage-dependent genes contribute to cell
      cycle, photosynthesis, and metabolism, whereas dosage-independent genes are
      enriched in biotic and abiotic stress responses. Interestingly, dosage-dependent
      genes tend to be preserved in ancient biochemical pathways present in both plant
      and nonplant species, whereas many dosage-independent genes belong to plant
      specific pathways. This is confirmed by an independent analysis using Arabidopsis
      phylostratigraphic map. For A. thaliana loci, the dosage-dependent alleles are
      devoid of TEs and tend to correlate with H3K9ac, H3K4me3, and CG methylation,
      whereas the majority of dosage-independent alleles are enriched with TEs and
      correspond to H3K27me1, H3K27me3, and CHG (H = A, T, or C) methylation.
      Furthermore, there is a parent-of-origin effect on nonadditively expressed genes
      in the reciprocal allotetraploids especially when A. arenosa is used as the
      pollen donor, leading to metabolic and morphological changes. Thus, ploidy,
      epigenetic modifications, and cytoplasmic-nuclear interactions shape gene
      expression diversity in polyploids. Dosage-dependent expression can maintain
      growth and developmental stability, whereas dosage-independent expression can
      facilitate functional divergence between homeologs (subfunctionalization and/or
      neofunctionalization) during polyploid evolution. 

PMID- 25976352
TI  - Background Mutational Features of the Radiation-Resistant Bacterium Deinococcus
      radiodurans.
AB  - Deinococcus bacteria are extremely resistant to radiation, oxidation, and
      desiccation. Resilience to these factors has been suggested to be due to enhanced
      damage prevention and repair mechanisms, as well as highly efficient antioxidant
      protection systems. Here, using mutation-accumulation experiments, we find that
      the GC-rich Deinococcus radiodurans has an overall background genomic mutation
      rate similar to that of E. coli, but differs in mutation spectrum, with the A/T
      to G/C mutation rate (based on a total count of 88 A:T -> G:C transitions and 82
      A:T -> C:G transversions) per site per generation higher than that in the other
      direction (based on a total count of 157 G:C -> A:T transitions and 33 G:C -> T:A
      transversions). We propose that this unique spectrum is shaped mainly by the
      abundant uracil DNA glycosylases reducing G:C -> A:T transitions, adenine
      methylation elevating A:T -> C:G transversions, and absence of cytosine
      methylation decreasing G:C -> A:T transitions. As opposed to the greater than
      100* elevation of the mutation rate in MMR(-) (DNA Mismatch Repair deficient)
      strains of most other organisms, MMR(-) D. radiodurans only exhibits a 4-fold
      elevation, raising the possibility that other DNA repair mechanisms compensate
      for a relatively low-efficiency DNA MMR pathway. As D. radiodurans has plentiful
      insertion sequence (IS) elements in the genome and the activities of IS elements
      are rarely directly explored, we also estimated the insertion (transposition)
      rate of the IS elements to be 2.50 * 10(-3) per genome per generation in the wild
      type strain; knocking out MMR did not elevate the IS element insertion rate in
      this organism.

PMID- 25976353
TI  - Dynamic and Widespread lncRNA Expression in a Sponge and the Origin of Animal
      Complexity.
AB  - Long noncoding RNAs (lncRNAs) are important developmental regulators in
      bilaterian animals. A correlation has been claimed between the lncRNA repertoire
      expansion and morphological complexity in vertebrate evolution. However, this
      claim has not been tested by examining morphologically simple animals. Here, we
      undertake a systematic investigation of lncRNAs in the demosponge Amphimedon
      queenslandica, a morphologically simple, early-branching metazoan. We combine RNA
      Seq data across multiple developmental stages of Amphimedon with a filtering
      pipeline to conservatively predict 2,935 lncRNAs. These include intronic
      overlapping lncRNAs, exonic antisense overlapping lncRNAs, long intergenic
      nonprotein coding RNAs, and precursors for small RNAs. Sponge lncRNAs are
      remarkably similar to their bilaterian counterparts in being relatively short
      with few exons and having low primary sequence conservation relative to protein
      coding genes. As in bilaterians, a majority of sponge lncRNAs exhibit typical
      hallmarks of regulatory molecules, including high temporal specificity and
      dynamic developmental expression. Specific lncRNA expression profiles correlate
      tightly with conserved protein-coding genes likely involved in a range of
      developmental and physiological processes, such as the Wnt signaling pathway.
      Although the majority of Amphimedon lncRNAs appears to be taxonomically
      restricted with no identifiable orthologs, we find a few cases of conservation
      between demosponges in lncRNAs that are antisense to coding sequences. Based on
      the high similarity in the structure, organization, and dynamic expression of
      sponge lncRNAs to their bilaterian counterparts, we propose that these noncoding
      RNAs are an ancient feature of the metazoan genome. These results are consistent
      with lncRNAs regulating the development of animals, regardless of their level of
      morphological complexity. 

PMID- 25976355
TI  - Closing calls to a cancer helpline: Expressions of caller satisfaction.
AB  - OBJECTIVE: This study provides an alternative approach to assessing caller
      satisfaction focussing on how callers express their appreciation of the service
      provided during the call, as the calls draw to a close. METHODS: Conversation
      analysis is used to analyse 99 calls between callers and cancer specialist nurses
      on a leading cancer helpline in the UK. RESULTS: Caller satisfaction is expressed
      through upgraded forms of the appreciations through which callers begin to close
      the call. Dissatisfaction is conveyed in what are by comparison with expressions
      of satisfaction, downgraded forms which acknowledge but do not fully or
      enthusiastically appreciate the information/advice given. With latter calls,
      nurses begin to 're-open' aspects of information/advice giving, thereby leading
      to more protracted call closings. CONCLUSION: Endogenous indicators of caller
      satisfaction are displayed through callers' upgraded appreciations in the closing
      moments of helpline calls. Difficulties in terminating calls (protracted by
      nurses re-opening information-giving etc.) arise when callers do not convey their
      satisfaction with the service provided. PRACTICE IMPLICATIONS: An understanding
      of endogenous indicators of satisfaction may benefit helpline organisations and
      further their understanding of effective call-handling, particularly through
      identifying the features common to those calls in which callers do not display
      their satisfaction with the call.

PMID- 25976356
TI  - Expression profiles of select genes in cumulus-oocyte complexes from young and
      aged mares.
AB  - There is compelling evidence that oocytes from mares >18 years of age have a high
      incidence of inherent defects that result in early embryonic loss. In women, an
      age-related decrease in oocyte quality is associated with an increased incidence
      of aneuploidy and it has recently been determined that the gene expression
      profile of human oocytes is altered with advancing age. We hypothesised that
      similar age-related aberrations in gene expression occur in equine oocytes.
      Therefore, the aim of the present study was to compare gene expression profiles
      of individual oocytes and cumulus cells from young and aged mares, specifically
      evaluating genes that have been identified as being differentially expressed with
      advancing maternal age and/or aneuploidy in human oocytes. Expression of 48 genes
      was compared between 14 cumulus-oocyte complexes (COCs) from mares aged 3-12
      years and 10 COCs from mares >=18 years of age. Three genes (mitochondrial
      translational initiation factor 3 (IF3), heat shock transcription factor 5 (HSF5)
      and Y box binding protein 2 (YBX2)) were differentially expressed in oocytes,
      with all being more abundant in oocytes from young mares. Three genes (ADP
      ribosylation factor-like 6 interacting protein 6 (ARL6IP6), BCL2-associated X
      protein (BAX) and hypoxia upregulated 1 (HYOU1)) were differentially expressed in
      cumulus cells, with all being more abundant in aged mares. The results of the
      present study confirm there are age-related differences in gene expression in
      equine COCs, which may be associated with the lower quality and decreased
      developmental competence of oocytes from aged mares. 

PMID- 25976354
TI  - Human Enhancers Are Fragile and Prone to Deactivating Mutations.
AB  - To explore the underlying mechanisms whereby noncoding variants affect
      transcriptional regulation, we identified nucleotides capable of disrupting
      binding of transcription factors and deactivating enhancers if mutated (dubbed
      candidate killer mutations or KMs) in HepG2 enhancers. On average, approximately
      11% of enhancer positions are prone to KMs. A comparable number of enhancer
      positions are capable of creating de novo binding sites via a single-nucleotide
      mutation (dubbed candidate restoration mutations or RSs). Both KM and RS
      positions are evolutionarily conserved and tend to form clusters within an
      enhancer. We observed that KMs have the most deleterious effect on enhancer
      activity. In contrast, RSs have a smaller effect in increasing enhancer activity.
      Additionally, the KMs are strongly associated with liver-related Genome Wide
      Association Study traits compared with other HepG2 enhancer regions. By applying
      our framework to lymphoblastoid cell lines, we found that KMs underlie
      differential binding of transcription factors and differential local chromatin
      accessibility. The gene expression quantitative trait loci associated with the
      tissue-specific genes are strongly enriched in KM positions. In summary, we
      conclude that the KMs have the greatest impact on the level of gene expression
      and are likely to be the causal variants of tissue-specific gene expression and
      disease predisposition. 

PMID- 25976357
TI  - Clearing the confusion around processed food addiction.

PMID- 25976358
TI  - Effect of PEO coating on bubble behavior within a polycarbonate microchannel
      array: A model for hemodialysis.
AB  - Obstruction of fluid flow by stationary bubbles in a microchannel hemodialyzer
      decreases filtration performance and increases damage to blood cells through flow
      maldistribution. A polyethylene oxide (PEO)-polybutadiene (PB)-polyethylene oxide
      surface modification, previously shown to reduce protein fouling and water/air
      contact angle in polycarbonate microchannel hemodialyzers, can improve
      microchannel wettability and may reduce bubble stagnation by lessening the
      resistive forces that compete with fluid flow. In this study, the effect of the
      PEO-PB-PEO coating on bubble retention in a microchannel array was investigated.
      Polycarbonate microchannel surfaces were coated with PEO-PB-PEO triblock polymer
      via radiolytic grafting. Channel obstruction was measured for coated and uncoated
      microchannels after injecting a short stream of air bubbles into the device under
      average nominal water velocities of 0.9 to 7.2 cm/s in the channels. The presence
      of the PEO coating reduced obstruction of microchannels by stationary bubbles
      within the range of 1.8 to 3.6 cm/s, average nominal velocity. Numerical
      simulations based on the lattice Boltzmann method indicate that beneficial
      effects may be due to the maintenance of a lubricating, thin liquid film around
      the bubble. The determined effective range of the PEO coating for bubble
      management serves as an important design constraint. These findings serve to
      validate the multiutility of the PEO-PB-PEO coating (bubble lubrication,
      biocompatibility, and therapeutic loading). (c) 2015 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 104B: 941-948, 2016.

PMID- 25976359
TI  - A framework to guide the conservation of species hybrids based on ethical and
      ecological considerations.
AB  - Species hybrids have long been undervalued in conservation and are often
      perceived as a threat to pure species. Recently, the conservation value of
      hybrids, especially those of natural origin, has gained recognition; however,
      hybrid conservation remains controversial. We reviewed hybrid management
      policies, including laws, regulations, and management protocols, from a variety
      of organizations, primarily in Canada and the United States. We found that many
      policies are based on limited ethical and ecological considerations and provide
      little opportunity for hybrid conservation. In most policies, hybrids are either
      unrepresented or considered a threat to conservation goals. This is problematic
      because our review of the hybrid conservation literature identified many ethical
      and ecological considerations relevant to determining the conservation value of a
      hybrid, all of which are management-context specific. We also noted a lack of
      discussion of the ethical considerations regarding hybrid conservation. Based on
      these findings, we created a policy framework outlining situations in which
      hybrids could be eligible for conservation in Canada and the United States. The
      framework comprises a decision tree that helps users determine whether a hybrid
      should be eligible for conservation based on multiple ecological and ethical
      considerations. The framework may be applied to any hybrid and is flexible in
      that it accommodates context-specific management by allowing different options if
      a hybrid is a threat to or could benefit conservation goals. The framework can
      inform policy makers and conservationists in decision-making processes regarding
      hybrid conservation by providing a systematic set of decision criteria and
      guidance on additional criteria to be considered in cases of uncertainty, and it
      fills a policy gap that limits current hybrid management. 

PMID- 25976360
TI  - Export of radioactive cesium from agricultural fields under simulated rainfall in
      Fukushima.
AB  - In this study, we investigated the impact of rainfall on runoff, soil erosion and
      consequently on the discharge of radioactive cesium in agricultural fields in
      Fukushima prefecture using a rainfall simulator. Simulated heavy rainfalls (50 mm
      h(-1)) generated significant runoff and soil erosion. The average concentration
      of radioactive cesium (the sum of (134)Cs and (137)Cs) in the runoff sediments
      was ~3500 Bq kg(-1) dry soil, more than double the concentrations measured in the
      field soils which should be considered in studies using the (137)Cs loss to
      estimate long-term soil erosion. However, the estimated mass of cesium discharged
      through one runoff event was less than 2% of the cesium inventory in the field.
      This suggested that cesium discharge via soil erosion is not a significant factor
      in reducing the radioactivity of contaminated soils in Fukushima prefecture.
      However, the eroded sediment carrying radioactive cesium will deposit into the
      river systems and potentially pose a radioactivity risk for aquatic living
      organisms. 

PMID- 25976361
TI  - Tertiary paediatric emergency department use in children and young people with
      cerebral palsy.
AB  - AIMS: The aim of this study was to describe the pattern of tertiary paediatric
      emergency department (ED) use in children and young people with cerebral palsy
      (CP). METHODS: A retrospective analysis of ED data routinely collected at the two
      tertiary paediatric hospitals in Victoria, Australia, cross-matched with the
      Victorian Cerebral Palsy Register. Data pertaining to the ED presentations of
      2183 registered individuals born 1993-2008 were obtained. RESULTS: Between 2008
      and 2012, 37% (n = 814) of the CP cohort had 3631 tertiary paediatric ED
      presentations. Overall, 40% (n = 332) of presenters were residing in inner
      metropolitan Melbourne; 44% (n = 356) in outer Melbourne; and 13% (n = 108) in
      regional Victoria. Presenters were more likely than non-presenters to be younger,
      non-ambulant and have epilepsy. In total, 71% of presentations were triaged as
      Australasian Triage Scale 1-3 (urgent), and 44% resulted in a hospital admission.
      Disorders of the respiratory, neurological and gastrointestinal systems, and
      medical device problems were responsible for 72% of presentations. CONCLUSION:
      Many of the tertiary paediatric ED presentations in this group were appropriate
      based on the high admission rate and the large proportion triaged as urgent.
      However, there is evidence that some families are bypassing local services and
      travelling long distances to attend the tertiary paediatric ED, even for less
      urgent complaints that do not require hospital admission. Alternative pathways of
      care delivery, and strategies to promote the management of common problems
      experienced by children and young people with CP in non-paediatric EDs or primary
      care settings, may go some way towards reducing unnecessary tertiary paediatric
      ED use in this group.

PMID- 25976362
TI  - [Not Available].

PMID- 25976363
TI  - [Not Available].

PMID- 25976364
TI  - Retinoic acid homeostasis through aldh1a2 and cyp26a1 mediates meiotic entry in
      Nile tilapia (Oreochromis niloticus).
AB  - Meiosis is a process unique to the differentiation of germ cells. Retinoic acid
      (RA) is the key factor controlling the sex-specific timing of meiotic initiation
      in tetrapods; however, the role of RA in meiotic initiation in teleosts has
      remained unclear. In this study, the genes encoding RA synthase aldh1a2, and
      catabolic enzyme cyp26a1 were isolated from Nile tilapia (Oreochromis niloticus),
      a species without stra8. The expression of aldh1a2 was up-regulated and
      expression of cyp26a1 was down-regulated before the meiotic initiation in ovaries
      and in testes. Treatment with RA synthase inhibitor or disruption of Aldh1a2 by
      CRISPR/Cas9 resulted in delayed meiotic initiation, with simultaneous down
      regulation of cyp26a1 and up-regulation of sycp3. By contrast, treatment with an
      inhibitor of RA catabolic enzyme and disruption of cyp26a1 resulted in earlier
      meiotic initiation, with increased expression of aldh1a2 and sycp3. Additionally,
      treatment of XY fish with estrogen (E2) and XX fish with fadrozole led to sex
      reversal and reversion of meiotic initiation. These results indicate that RA is
      indispensable for meiotic initiation in teleosts via a stra8 independent
      signaling pathway where both aldh1a2 and cyp26a1 are critical. In contrast to
      mammals, E2 is a major regulator of sex determination and meiotic initiation in
      teleosts. 

PMID- 25976365
TI  - Role of Wnt Signaling in Central Nervous System Injury.
AB  - The central nervous system (CNS) is highly sensitive to external mechanical
      damage, presenting a limited capacity for regeneration explained in part by its
      inability to restore either damaged neurons or the synaptic network. The CNS may
      suffer different types of external injuries affecting its function and/or
      structure, including stroke, spinal cord injury, and traumatic brain injury.
      These pathologies critically affect the quality of life of a large number of
      patients worldwide and are often fatal because available therapeutics are
      ineffective and produce limited results. Common effects of the mentioned
      pathologies involves the triggering of several cellular and metabolic responses
      against injury, including infiltration of blood cells, inflammation, glial
      activation, and neuronal death. Although some of the underlying molecular
      mechanisms of those responses have been elucidated, the mechanisms driving these
      processes are poorly understood in the context of CNS injury. In the last few
      years, it has been suggested that the activation of the Wnt signaling pathway
      could be important in the regenerative response after CNS injury, activating
      diverse protective mechanisms including the stimulation of neurogenesis, blood
      brain structure consolidation and the recovery of cognitive brain functions.
      Because Wnt signaling is involved in several physiological processes, the
      putative positive role of its activation after injury could be the basis for
      novel therapeutic approaches to CNS injury. 

PMID- 25976366
TI  - GNE Myopathy and Cell Apoptosis: A Comparative Mutation Analysis.
AB  - In a number of genetic disorders such as GNE myopathy, it is not clear how
      mutations in target genes result in disease phenotype. GNE myopathy is a
      progressive neuro-degenerative disorder associated with homozygous or compound
      heterozygous missense mutations in either epimerase or kinase domain of UDP
      GlcNAc 2-epimerase/ManNAc kinase (GNE). This bifunctional enzyme catalyses the
      rate limiting step in sialic acid biosynthesis. Many mechanisms have been
      suggested as possible cause of muscle degeneration. These include hyposialylation
      of critical proteins, defects in cytoskeletal network, sarcomere organization and
      apoptosis. In order to elucidate the role of GNE in cell apoptosis, we have used
      HEK cell-based model system overexpressing pathologically relevant GNE mutations.
      These cells display a reduction in the levels of sialic acid-bound
      glycoconjugates. These mutants GNE overexpressing cells have defect in cell
      proliferation as compared to vector or wild-type GNE (wtGNE) controls. Moreover,
      effect of different GNE mutations on cell apoptosis was also observed using
      staining with annexin V-FITC and TUNEL assay. The downstream apoptosis signalling
      pathway involving activation of caspases and increased PARP cleavage were
      observed in all GNE mutant cell lines. In addition, morpho-structural changes in
      mitochondria in cells overexpressing different GNE mutants were noticed by
      transmission electron microscopy, and mitochondrial transmembrane potential was
      found to be altered in absence of functional GNE. Our results clearly indicate
      role of GNE in mitochondria-dependent cell apoptosis and provide insights into
      the pathomechanism of GNE myopathy.

PMID- 25976371
TI  - [Adjuvant chemotherapy for stage I lung cancer in the elderly].

PMID- 25976369
TI  - Neuroprotective Effect of JZL184 in MPP(+)-Treated SH-SY5Y Cells Through CB2
      Receptors.
AB  - Growing evidence suggests that the endocannabinoid system plays a role in
      neuroprotection in Parkinson's disease. Recently, we have shown the
      neuroprotective effect of monoacylglycerol lipase (MAGL) inhibition with JZL184
      in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model.
      However, further investigation is needed to determine the neuroprotective
      mechanisms of the endocannabinoid system on the nigrostriatal pathway. The aim of
      this work was to investigate whether the neuroprotective effect of JZL184 in mice
      could be extended to an in vitro cellular model to further understand the
      mechanism of action of the drug. The SH-SY5Y cell line was selected based on its
      dopaminergic-like phenotype and its susceptibility to 1-methyl-4-phenylpyridinium
      iodide (MPP(+)) toxicity. Furthermore, SH-SY5Y cells express both cannabinoid
      receptors, CB1 and CB2. The present study describes the neuroprotective effect of
      MAGL inhibition with JZL184 in SH-SY5Y cells treated with MPP(+). The effect of
      JZL184 in cell survival was blocked by AM630, a CB2 receptor antagonist, and it
      was mimicked with JWH133, a CB2 receptor agonist. Rimonabant, a CB1 receptor
      antagonist, did not affect JZL184-induced cell survival. These results
      demonstrate that the neuroprotective effect of MAGL inhibition with JZL184
      described in animal models of Parkinson's disease could be extended to in vitro
      models such as SH-SY5Y cells treated with MPP(+). This represents a useful tool
      to study mechanisms of neuroprotection mediated by MAGL inhibition, and we
      provide evidence for the possible involvement of CB2 receptors in the improvement
      of cell survival. 

PMID- 25976370
TI  - Neuroanatomical Visualization of the Impaired Striatal Connectivity in
      Huntington's Disease Mouse Model.
AB  - Huntington's disease (HD) is a movement disorder characterized by the early
      selective degeneration of striatum. For motor control, the striatum receives
      excitatory inputs from multiple brain regions and projects the information to
      other basal ganglia nuclei. Despite the pathological importance of the striatal
      degeneration in HD, there are little anatomical data that show impaired striatal
      connectivity in HD. For the anatomical mapping of the striatum, we injected here
      a neurotracer DiD to the dorsal striatum of HD mouse model (YAC128). Compared
      with littermate controls, the number of the traced inputs to the striatum was
      reduced dramatically in YAC128 mice at 12 months of age suggesting massive
      destruction of the striatal connections. Basal ganglia inputs were significantly
      damaged in HD mice by showing 61 % decrease in substantia nigra pars compacta,
      85% decrease in thalamic centromedian nucleus, and 55% decrease in thalamic
      parafascicular nucleus. Cortical inputs were also greatly decreased by 43% in
      motor cortex, 48% in somatosensory cortex, and 72% in visual cortex. Besides the
      known striatal connections, the neurotracer DiD also traced inputs from amygdala
      and the amygdala inputs were decreased by 68% in YAC128 mice. Considering the
      role of amygdala in emotion processing, the impairment in amygdalostriatal
      connectivity strongly suggests that emotional disturbances could occur in HD
      mice. Indeed, open-field tests further indicated that YAC128 mice exhibited
      changes in emotional behaviors related to symptoms of depression and anxiety.
      Although onset of HD is clinically determined on the basis of motor abnormality,
      emotional deficits are also common features of the disease. Therefore, our
      anatomical connectivity mapping of the striatum provides a new insight to
      interpret brain dysfunction in HD.

PMID- 25976368
TI  - The Role of Oxidized Cholesterol in Diabetes-Induced Lysosomal Dysfunction in the
      Brain.
AB  - Abnormalities in lysosomal function have been reported in diabetes, aging, and
      age-related degenerative diseases. These lysosomal abnormalities are an early
      manifestation of neurodegenerative diseases and often precede the onset of
      clinical symptoms such as learning and memory deficits; however, the mechanism
      underlying lysosomal dysfunction is not known. In the current study, we
      investigated the mechanism underlying lysosomal dysfunction in the cortex and
      hippocampi, key structures involved in learning and memory, of a type 2 diabetes
      (T2D) mouse model, the leptin receptor deficient db/db mouse. We demonstrate for
      the first time that diabetes leads to destabilization of lysosomes as well as
      alterations in the protein expression, activity, and/or trafficking of two
      lysosomal enzymes, hexosaminidase A and cathepsin D, in the hippocampus of db/db
      mice. Pioglitazone, a thiazolidinedione (TZD) commonly used in the treatment of
      diabetes due to its ability to improve insulin sensitivity and reverse
      hyperglycemia, was ineffective in reversing the diabetes-induced changes on
      lysosomal enzymes. Our previous work revealed that pioglitazone does not reverse
      hypercholesterolemia; thus, we investigated whether cholesterol plays a role in
      diabetes-induced lysosomal changes. In vitro, cholesterol promoted the
      destabilization of lysosomes, suggesting that lysosomal-related changes
      associated with diabetes are due to elevated levels of cholesterol. Since
      lysosome dysfunction precedes neurodegeneration, cognitive deficits, and
      Alzheimer's disease neuropathology, our results may provide a potential mechanism
      that links diabetes with complications of the central nervous system. 

PMID- 25976372
TI  - [Abiraterone: Overall survival benefit and subsidiary issues].

PMID- 25976367
TI  - Are microRNAs the Molecular Link Between Metabolic Syndrome and Alzheimer's
      Disease?
AB  - Alzheimer's disease (AD) is the most common cause of dementia in people over 65
      years of age. At present, treatment options for AD address only its symptoms, and
      there are no available treatments for the prevention or delay of the disease
      process. Several preclinical and epidemiological studies have linked metabolic
      risk factors such as hypertension, obesity, dyslipidemia, and diabetes to the
      pathogenesis of AD. However, the molecular mechanisms that underlie this
      relationship are not fully understood. Considering that less than 1% of cases of
      AD are attributable to genetic factors, the identification of new molecular
      targets linking metabolic risk factors to neuropathological processes is
      necessary for improving the diagnosis and treatment of AD. The dysregulation of
      microRNAs (miRNAs), small non-coding RNAs that regulate several biological
      processes, has been implicated in the development of different pathologies. In
      this review, we summarize some of the relevant evidence that points to the role
      of miRNAs in metabolic syndrome (MetS) and AD and propose that miRNAs may be a
      molecular link in the complex relationship between both diseases.

PMID- 25976374
TI  - Abstracts from the ASA 40(th) Annual Conference, 18-21 April 2015, Salt Lake
      City, Utah.

PMID- 25976373
TI  - Delta-like 4-mediated Notch signaling is required for early T-cell development in
      a three-dimensional thymic structure.
AB  - Delta-like 4 (Dll4)-mediated Notch signaling is critical for specifying T-cell
      fate, but how Dll4-mediated Notch signaling actually contributes to T-cell
      development in the thymus remains unclear. To explore this mechanism in the
      thymic three-dimensional structure, we performed fetal thymus organ culture using
      Dll4-deficient mice. DN1a/b+DN2mt cells, which had not yet committed to either
      the alphabeta T or gammadelta T/NK cell lineage, did not differentiate into the
      alphabeta T-cell lineage in Dll4-deficient thymus despite the lack of cell fate
      conversion into other lineages. However, DN3 cells efficiently differentiated
      into a later developmental stage of alphabeta T cells, the double-positive (DP)
      stage, although the proliferation was significantly impaired during the
      differentiation process. These findings suggest that the requirement for Notch
      signaling differs between the earliest and pre-TCR-bearing precursors and that
      continued Notch signaling is required for proper differentiation with active
      proliferation of alphabeta T lineage cells. Furthermore, we showed that Notch
      signaling increased the c-Myc expression in DN3 cells in the thymus and that its
      overexpression rescued the proliferation and differentiation of DN3 cells in the
      Dll4-null thymus. Therefore, c-Myc plays a central role in the transition from
      stage DN3 to DP as a downstream target of Notch signaling. 

PMID- 25976375
TI  - Diagnosis and laparoscopic management of a rare endometriosis-related peritoneal
      mass with rapid growth in early pregnancy.
AB  - Herein is described the diagnosis, clinical management and laparoscopic removal
      of a rapid growing retro-uterine mass in a pregnant woman. After laparoscopic
      removal of the pelvic mass, diagnosis of peritoneal endometriotic cyst was made
      on histology. The patient was asymptomatic and no history of endometriosis was
      reported. The laparoscopic management of the peritoneal mass was safe and
      effective and to our knowledge this is the first case report describing a
      decidualized endometriotic lesion in the absence of a pre-pregnancy endometriosis
      diagnosis.

PMID- 25976376
TI  - Community-Academic Partnership Participation.
AB  - Community-academic partnerships (CAPs) improve the research process, outcomes,
      and yield benefits for the community and researchers. This exploratory study
      examined factors important in community stakeholders' decision to participate in
      CAPs. Autism spectrum disorder (ASD) community stakeholders, previously contacted
      to participate in a CAP (n = 18), completed the 15-item Decision to Participate
      Questionnaire (DPQ). The DPQ assessed reasons for participating or declining
      participation in the ASD CAP. CAP participants rated networking with other
      providers, fit of collaboration with agency philosophy, and opportunity for
      future training/consultations as factors more important in their decision to
      participate in the ASD CAP than nonparticipants. Nonparticipants reported the
      number of requests to participate in research as more important in their decision
      to decline participation than participants. Findings reveal important factors in
      community stakeholders' decision to participate in CAPs that may provide guidance
      on increasing community engagement in CAPs and help close the science-to-service
      gap.

PMID- 25976377
TI  - Detection of cytomegalovirus, human parvovirus B19, and herpes simplex virus-1/2
      in women with first-trimester spontaneous abortions.
AB  - The relationship between viral infections and first-trimester spontaneous
      abortions is not well-understood. The study aim was to investigate the prevalence
      of cytomegalovirus (CMV), human parvovirus B19 (B19V), and herpes simplex virus
      1/2 (HSV-1/2) infection by molecular and serological techniques in women
      experiencing spontaneous miscarriage in the first trimester of pregnancy. Plasma
      samples were examined for CMV, B19V, and HSV-1/2 DNA using real-time quantitative
      polymerase chain reaction (Real-time qPCR), and for specific IgG antibodies
      against B19V, CMV, and HSV-1/2 using serological assays. The abortion group
      consisted of women (n = 1,716) with a history of two or more first-trimester
      spontaneous abortions. Women younger than 30 years possess higher portion to
      experience spontaneous abortion. No specimens were positive for B19V or CMV DNA.
      Seven out of the 1,716 specimens were positive for HSV-1/2 DNA. By serology,
      47.24% of patients were positive for B19V IgG, 39.66% for HSV IgG, 79.31% for CMV
      IgG, and 9.31% for B19V IgM. The high rate of positivity for CMV IgG suggests
      that the majority of women with first-trimester spontaneous abortions are not
      susceptible to primary CMV infection. The lack of virus DNA in the majority of
      cases indicates that B19V, CMV, and HSV-1/2 infection is not commonly associated
      with first-trimester spontaneous abortion.

PMID- 25976378
TI  - A Follow-Up Community Survey of Knowledge and Beliefs About Cancer and Genetics.
AB  - The purpose of this study is to assess changes since the launch of the US Surgeon
      General's campaign in the public's beliefs about the role of genetics in the
      etiology of cancer, as well as changes in recording family health history. We
      conducted a survey of 480 Western New York adults, assessing: (1) experiences
      with cancer, (2) beliefs about cancer and genetics, and (3) practices of
      recording family health history. Most respondents were aware of the importance of
      family history. The sample also showed increased knowledge about cancer and
      genetics compared with a previous survey. However, only 7 % kept written records
      that included medical conditions, which was not different from a previous survey.
      Time constraints, apathy, and reluctance to find out negative health information
      were the most reported barriers. Results suggest a need for continued education
      of the public, with increased emphasis on written family health records. 

PMID- 25976379
TI  - Administration of granulocyte colony-stimulating factor with radiotherapy
      promotes tumor growth by stimulating vascularization in tumor-bearing mice.
AB  - Although granulocyte-colony stimulating factor (G-CSF) is commonly used to
      support recovery from radiation-induced side-effects, the precise effects of G
      CSF on colon cancer under radiotherapy remain poorly understood. In the present
      study, to investigate the effects of tumor growth following radiotherapy and G
      CSF administration in a murine xenograft model of colon cancer, female BALB/c
      mice were injected with cells of a colon carcinoma cell line (CT26) with
      irradiation and G-CSF, alone or in combination. Mice received 2 Gy of focal
      radiation daily for 5 days and intraperitoneal injection of G-CSF (100 ug/kg/day)
      after irradiation for 7 days. Changes in the levels of myeloperoxidase (MPO),
      vascular endothelial growth factor (VEGF), matrix metalloproteinase type 9 (MMP
      9) and CD31 were assessed in the mouse cancer induced by injection of colon
      cancer cells. We observed that G-CSF increased the number of circulating
      neutrophils, but facilitated tumor growth. However, G-CSF treatment did not
      affect radiation-induced cytotoxicity and cell viability in CT26 cells in vitro.
      Increased levels of myeloperoxidase, a neutrophil marker and those of vascular
      endothelial growth factor were observed in tumors with G-CSF supplementation. In
      addition, we found that increased levels of CD31 and matrix metalloproteinase-9
      were correlated with the enhanced tumor growth after G-CSF treatment. Therefore,
      these data suggest that G-CSF may contribute to tumor growth and decrease the
      antitumor effect of radiotherapy, possibly by promoting vascularization in cancer
      lesions.

PMID- 25976380
TI  - Molecular characterization of resistance, virulence and clonality in vancomycin
      resistant Enterococcus faecium and Enterococcus faecalis: A hospital-based study
      in Beijing, China.
AB  - The incidence of vancomycin-resistant enterococcus (VRE) in China is increasing,
      the molecular epidemiology of VRE in China is only partly known. This study was
      conducted to assess the molecular characterization of resistance, virulence and
      clonality of 69 vancomycin-resistant Enterococcus faecium (VREfm) and seven
      vancomycin-resistant Enterococcus faecalis (VREfs) isolates obtained from a
      Chinese hospital between July 2011 and July 2013. The glycopeptide resistance
      genes (VanA and VanB) were screened by multiplex PCR. The presence of five
      putative virulence genes (esp, gelE, asa1, hyl and cylA) were evaluated by
      another multiplex PCR. Multilocus sequence typing (MLST) scheme was used to
      assess the clonality. All 76 VRE isolates exhibited VanA phenotype and harbored
      VanA gene. Esp was the only gene detected both in VREfm and VREfs strains,
      accounting for 89.9% and 42.9%, respectively. The hyl gene was merely positive in
      27.5% of VREfm strains. MLST analysis demonstrated three STs (ST6, ST4 and ST470)
      in VREfs and twelve STs (ST78, ST571, ST17, ST564, ST389, ST18, ST547, ST341,
      ST414, ST343, ST262 and ST203) in VREfm, which were all designated as CC17 by
      eBURST algorithm. An outbreak of VREfm belonging to ST571 was found to happen
      within the neurology ward in this hospital. To our knowledge, this is the first
      report of ST6 (CC2) VREfs strains in China and the first outbreak report of VREfm
      strains belonging to ST571 around the world. Our data could offer important
      information for understanding the molecular features of VRE in China. 

PMID- 25976381
TI  - Molecular characterization of macrolide resistant Streptococcus pyogenes isolates
      from pharyngitis patients in Serbia.
AB  - A steady increase in macrolide resistance in Streptococcus pyogenes, group A
      streptococci (GAS) was reported in Serbia during 2004-2009 (9.9%). However, there
      are no data on the molecular epidemiology of pharyngeal macrolide resistance GAS
      (MRGAS) isolates. Therefore, the aims of this first nationwide study were to
      examine the prevalence of macrolide resistance in Serbian GAS and to determine
      their resistance phenotypes, genotypes and clonal relationships. Overall 3893 non
      duplicate pharyngeal S. pyogenes isolates from outpatients with GAS infection
      were collected throughout country during 2008 and 2009. Among 486 macrolide
      resistant pharyngeal isolates collected, 103 were further characterized.
      Macrolide resistance phenotypes and genotypes were determined by double-disk
      diffusion test and PCR, respectively. Strain relatedness was determined by emm
      typing, multilocus sequence typing (MLST), multilocus variable tandem repeat
      analysis (MLVA), phage profiling (PP) and virulence factor profiling (VFP).
      Overall, macrolide resistance among GAS isolates in Serbia was 12.5%. M phenotype
      was the most common (71.8%), followed by iMLS (18.4%) and cMLS (9.7%). Three
      clonal complexes--emm75/mefA/ST49, emm12/mefA/ST36 and emm77/ermA/tetO/ST63
      comprised over 90% of the tested strains. Although MLVA, PP and VFP distinguished
      10, 20 and 12 different patterns, respectively, cluster analysis disclosed only
      small differences between strains which belonged to the same emm/ST type. Our
      data indicate dominance of three major internationally widely disseminated
      macrolide resistant clones and a high genetic homogeneity among the Serbian MRGAS
      population. Continued surveillance of macrolide resistance and clonal composition
      in MRGAS in Serbia in future is necessary to determine stability of MRGAS clones
      and to guide therapy strategies.

PMID- 25976382
TI  - Naturally occurring deletion/insertion mutations within HBV whole genome
      sequences in HBeAg-positive chronic hepatitis B patients are correlated with
      baseline serum HBsAg and HBeAg levels and might predict a shorter interval to
      HBeAg loss and seroconversion during antiviral treatment.
AB  - OBJECTIVES: Deletion/insertion (Del/Ins) throughout hepatitis B virus (HBV)
      genome has not been well studied for HBeA-positive chronic hepatitis B (CHB)
      patients. This study aimed to characterize the HBV Del/Ins mutations in full
      length genome quasispecies sequences in such patients at antiviral baseline and
      to reveal their potential impacts on HBV serological markers and responses to
      nucleos(t)ide analogue (NUC) treatment. MATERIALS AND METHODS: A total of 30
      HBeAg-positive CHB patients with genotype C infection receiving a 104-week
      lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled.
      HBV whole genome sequences in serum samples at baseline were clone sequenced and
      analyzed using bioinformatics tools. RESULTS: Among 306 unspliced clone
      sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full
      length genomes without any Del/Ins. Due to different combinations of 125 deletion
      types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome
      patterns, which affected a single or several functional genomic regions.
      Importantly, the proportion of Del/Ins-harboring clones was found to be
      significantly negatively correlated with HBsAg (r = -0.3985, P = 0.0292) and
      HBeAg (r = -0.3878, P = 0.0342) at baseline. Higher percentage of Del/Ins
      harboring clones at baseline was found to predict a shorter interval to HBeAg
      loss and seroconversion. CONCLUSION: Del/Ins mutations within HBV whole genome
      were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A
      higher detection rate of these mutations at baseline might correlate with a
      better response to LMV and ADV combination therapy.

PMID- 25976383
TI  - End of induction minimal residual disease alone is not a useful determinant for
      risk stratified therapy in pediatric T-cell acute lymphoblastic leukemia.
AB  - The role of end of induction minimal residual disease (MRD) as determined by flow
      cytometry for treatment assignment in pediatric T-cell acute lymphoblastic
      leukemia (T-ALL) is not well defined. We studied 33 children with newly diagnosed
      T-ALL. Thirty-two of 33 patients remain in continuous complete remission at a
      median of 4 years. Nineteen patients were MRD positive at the end of induction
      and all remain in remission with augmented Berlin Frankfurt Munster-based
      therapy. One patient underwent hematopoietic stem cell transplant for rising MRD.
      Persistent end of induction MRD alone is not an indication to alter therapy in
      pediatric T-ALL.

PMID- 25976385
TI  - Neurodegenerative disease: Phosphatase inhibitor prevents protein-misfolding
      diseases.

PMID- 25976384
TI  - Seasonal changes in prescribing of long-acting beta-2-agonists-containing drugs.
AB  - BACKGROUND: For patients with asthma, COPD, or asthma-COPD overlap syndrome
      (ACOS), inter-country comparisons of seasonal changes in drug prescriptions are
      scarce or missing. Hence, we aimed to compare seasonal changes in prescription
      rates of long-acting beta-2-agonist (LABA) in four European countries. METHODS: A
      common study protocol was applied to six health care databases (Germany, Spain,
      the Netherlands (2), and the UK (2)) to calculate age- and sex-standardized point
      prevalence rates (PPRs) of LABA-containing prescriptions by the 1st of March,
      June, September, and December of each year during the study period 2002-2009.
      Seasonal variation of PPRs was quantified using seasonal indexes (SIs; based on
      the ratio-to-moving-average-method) and SIs averaged over the study period (aSI)
      stratified by sex, age, and indication (asthma, COPD, or ACOS). RESULTS: There
      was a moderate seasonal change in LABA-containing prescriptions which was more
      pronounced in asthma or COPD patients compared to ACOS patients. For asthma and
      ACOS patients, highest seasonal variation was found for patients living in Spain
      (aSI: 87.3-110.7, aSI: 93.2-103.1) whereas for COPD highest seasonal variation
      was revealed for the NPCRD database (the Netherlands) (aSI: 92.2-105.6).
      Regarding age and sex, highest seasonal variation was found in Spanish boys under
      10 years of age having a diagnosis of asthma. CONCLUSIONS: By applying a common
      analysis in six databases, we could observe moderate overall seasonal changes in
      LABA-containing prescription rates in patients with asthma, COPD, or ACOS.

PMID- 25976387
TI  - Respiratory diseases: Breathing easy with calcilytics.

PMID- 25976389
TI  - The chronic lymphocytic leukaemia market.

PMID- 25976391
TI  - Non-target screening with high-resolution mass spectrometry: critical review
      using a collaborative trial on water analysis.
AB  - In this article, a dataset from a collaborative non-target screening trial
      organised by the NORMAN Association is used to review the state-of-the-art and
      discuss future perspectives of non-target screening using high-resolution mass
      spectrometry in water analysis. A total of 18 institutes from 12 European
      countries analysed an extract of the same water sample collected from the River
      Danube with either one or both of liquid and gas chromatography coupled with mass
      spectrometry detection. This article focuses mainly on the use of high resolution
      screening techniques with target, suspect, and non-target workflows to identify
      substances in environmental samples. Specific examples are given to emphasise
      major challenges including isobaric and co-eluting substances, dependence on
      target and suspect lists, formula assignment, the use of retention information,
      and the confidence of identification. Approaches and methods applicable to unit
      resolution data are also discussed. Although most substances were identified
      using high resolution data with target and suspect-screening approaches, some
      participants proposed tentative non-target identifications. This comprehensive
      dataset revealed that non-target analytical techniques are already substantially
      harmonised between the participants, but the data processing remains time
      consuming. Although the objective of a "fully-automated identification workflow"
      remains elusive in the short term, important steps in this direction have been
      taken, exemplified by the growing popularity of suspect screening approaches.
      Major recommendations to improve non-target screening include better integration
      and connection of desired features into software packages, the exchange of target
      and suspect lists, and the contribution of more spectra from standard substances
      into (openly accessible) databases. Graphical Abstract Matrix of identification
      approach versus identification confidence. 

PMID- 25976392
TI  - Improvement of chlorophyll identification in foodstuffs by MALDI ToF/ToF mass
      spectrometry using 1,5-diaminonaphthalene electron transfer secondary reaction
      matrix.
AB  - Chlorophylls (Chls) are important pigments responsible for the characteristic
      green color of chloroplasts in algae and plants. In this study, 1,5
      diaminonaphthalene (DAN) was introduced as an electron transfer secondary
      reaction matrix for the identification of intact chlorophylls and their
      derivatives, by matrix-assisted laser desorption ionization (MALDI) mass
      spectrometry (MS). DAN was proved to drastically outperform conventional matrices
      such as alpha-cyano-4-hydroxycinnnamic acid, dithranol, antracene, and even
      terthiophene, since loss of the metal ion and fragmentation of the phytol-ester
      linkage are negligible. Absence of significant fragmentation of radical cations
      of Chls a and b at m/z 892.529 and 906.513, respectively, makes MALDI MS capable
      of following natural degradation of intact porphyrin-based pigments whose initial
      steps are just represented by demetalation and dephytylation. Chl by-products,
      such as pyropheophytins, have been identified in dried tea leaves showing the
      potential of MALDI MS to follow chlorophyll biotransformation occurring in
      processed foodstuffs. Finally, preliminary results show the potential of MALDI MS
      to detect illegal vegetable oil re-greening practices. 

PMID- 25976393
TI  - In situ DRIFT, Raman, and XRF implementation in a multianalytical methodology to
      diagnose the impact suffered by built heritage in urban atmospheres.
AB  - This work addresses the evaluation of an innovative mutianalytical method to
      assess the conservation state of a fifteenth century palace house. With the goal
      of reducing the handicaps of field analysis, the in situ spectroscopic
      assessment, often based on the use of X-ray fluorescence and Raman spectrometers,
      was complemented by the use of diffuse reflectance infrared Fourier transform
      spectroscopy. In this manner, its usefulness as a diagnostic tool to discover the
      origin and mechanisms of the damage caused by atmospheric and infiltration water
      attacks were thoroughly examined. Moreover, the study was extended in the
      laboratory to increase the information obtained by nondestructive techniques. The
      results revealed a severe material loss caused by soluble salts. Thus, a
      noninvasive sampling method using cellulose patches was tested to study the
      amount and mobility of salts by means of ion chromatography. Finally, to
      establish the chemical degradation processes that are occurring in the palace, a
      chemometric analysis of the quantitative data as well as the construction of
      thermodynamic models was done to advise on the required restorative actions.
      Graphical Abstract The different phases of the multianalytical method to assess
      the conservation state of built heritage. 

PMID- 25976394
TI  - Data-driven signal-resolving approaches of infrared spectra to explore the
      macroscopic and microscopic spatial distribution of organic and inorganic
      compounds in plant.
AB  - The nondestructive and label-free infrared (IR) spectroscopy is a direct tool to
      characterize the spatial distribution of organic and inorganic compounds in
      plant. Since plant samples are usually complex mixtures, signal-resolving methods
      are necessary to find the spectral features of compounds of interest in the
      signal-overlapped IR spectra. In this research, two approaches using existing
      data-driven signal-resolving methods are proposed to interpret the IR spectra of
      plant samples. If the number of spectra is small, "tri-step identification" can
      enhance the spectral resolution to separate and identify the overlapped bands.
      First, the envelope bands of the original spectrum are interpreted according to
      the spectra-structure correlations. Then the spectrum is differentiated to
      resolve the underlying peaks in each envelope band. Finally, two-dimensional
      correlation spectroscopy is used to enhance the spectral resolution further. For
      a large number of spectra, "tri-step decomposition" can resolve the spectra by
      multivariate methods to obtain the structural and semi-quantitative information
      about the chemical components. Principal component analysis is used first to
      explore the existing signal types without any prior knowledge. Then the spectra
      are decomposed by self-modeling curve resolution methods to estimate the spectra
      and contents of significant chemical components. At last, targeted methods such
      as partial least squares target can explore the content profiles of specific
      components sensitively. As an example, the macroscopic and microscopic
      distribution of eugenol and calcium oxalate in the bud of clove is studied. 

PMID- 25976395
TI  - ANAKON 2015 in Graz: a warm welcome for analytical chemists in the heart of
      Styria.

PMID- 25976396
TI  - Exploration of optical fibres as a carrier for new benzene and toluene matrix
      free reference materials.
AB  - To meet high expectations concerning precision and accuracy of reference
      materials, preparation of matrix-free reference materials using thermal
      decomposition-gas chromatography-mass spectrometry (TD-GC-MS) was proposed in
      this study. In the paper, the results obtained in preparation of the new
      reference materials for benzene and toluene are presented, based on the thermal
      decomposition technique of compounds chemically bound to the surface of optical
      fibre segments. The results obtained at various stages of the research procedure
      (homogeneity, stability) confirmed the possibility of using prepared laboratory
      samples of materials as reference materials for benzene and toluene. For the
      prepared batch of materials, reference values 1.26 +/- 0.91 (ng/fibre) for
      benzene and 11.3 +/- 7.4 (ng/fibre) for toluene were determined. 

PMID- 25976397
TI  - Structure the Process, Not Just Your Final Report.

PMID- 25976398
TI  - CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement.

PMID- 25976399
TI  - Risk stratification and outcomes of women undergoing surgery for ovarian cancer.
AB  - OBJECTIVE: Cytoreduction for ovarian cancer is associated with substantial
      morbidity. We examined the outcome of patients undergoing surgery for ovarian
      cancer to determine if there are sub-groups of patients who may benefit from
      alternative treatments. METHODS: The National Surgical Quality Improvement
      Program database was used to identify women who underwent surgery for ovarian
      cancer from 2005-2012. Multivariable logistic regression models were used to
      examine the effect of age, race, functional status, ASA class, preoperative
      albumin and performance of extended cytoreductive procedures on morbidity,
      mortality and resource utilization. RESULTS: A total of 2870 women were
      identified. The perioperative complication rate increased from 9.5% in women
      <50years, to 13.4% in those age 60-69years, and 14.6% in women >=70years
      (P<0.0001). Similarly, complications rose from 7.3% in those who did not require
      any extended procedures to 12.9% after 1 procedure, 28.4% for those who had 2,
      and 30.0% in women who underwent >=3 extended procedures (P<0.0001). In a series
      of multivariable models, the number of extended cytoreductive procedures
      performed and preoperative albumin were the factors most consistently associated
      with morbidity. Using a series of model fit statistics, compared to chance alone,
      the ability to predict any complication increased by 27.4% when procedure score
      was analyzed, 22.0% with preoperative albumin, 11% with age, and 4% with
      functional status. CONCLUSIONS: While preoperative clinical and demographic
      factors may help predict the risk of adverse outcomes for women undergoing
      surgery for ovarian cancer, performance of extended cytoreductive procedures is
      the strongest risk factor for complications.

PMID- 25976401
TI  - International Headache Society abstracts.

PMID- 25976400
TI  - Population density and climate shape early-life survival and recruitment in a
      long-lived pelagic seabird.
AB  - 1. Our understanding of demographic processes is mainly based on analyses of
      traits from the adult component of populations. Early-life demographic traits are
      poorly known mainly for methodological reasons. Yet, survival of juvenile and
      immature individuals is critical for the recruitment into the population and thus
      for the whole population dynamic, especially for long-lived species. This bias
      currently restrains our ability to fully understand population dynamics of long
      lived species and life-history theory. 2. The goal of this study was to estimate
      the early-life demographic parameters of a long-lived species with a long
      immature period (9-10 years), to test for sex and age effects on these parameters
      and to identify the environmental factors encountered during the period of
      immaturity that may influence survival and recruitment. 3. Using capture-mark
      recapture multievent models allowing us to deal with uncertain and unobservable
      individual states, we analysed a long-term data set of wandering albatrosses to
      estimate both age- and sex-specific early-life survival and recruitment. We
      investigated environmental factors potentially driving these demographic traits
      using climatic and fisheries covariates and tested for density dependence. 4. Our
      study provides for the first time an estimate of annual survival during the first
      2 years at sea for an albatross species (0.801 +/- 0.014). Both age and sex
      affected early-life survival and recruitment processes of this long-lived seabird
      species. Early-life survival and recruitment were highly variable across years
      although the sensitivity of young birds to environmental variability decreased
      with age. Early-life survival was negatively associated with sea surface
      temperature, and recruitment rate was positively related to both Southern Annular
      Mode and sea surface temperature. We found strong evidence for density-dependent
      mortality of juveniles. Population size explained 41% of the variation of this
      parameter over the study period. 5. These results indicate that early-life
      survival and recruitment were strongly age and sex dependent in a dimorphic long
      lived species. In addition, early-life demographic parameters were affected by
      natal environmental conditions and by environmental conditions faced during the
      period of immaturity. Finally, our results constitute one of the first
      demonstrations of density dependence on juvenile survival in seabirds, with major
      consequences for our understanding of population dynamics in seabirds.

PMID- 25976403
TI  - Postprostatectomy Radiotherapy for Patients with High-risk Features on Definitive
      Pathology: A Plea for Evidence-based Medicine.

PMID- 25976404
TI  - Network of co-mutations in Ebola virus genome predicts the disease lethality.

PMID- 25976406
TI  - miR-27a rs895819 polymorphism and risk of cancer in Chinese population: a meta
      analysis.
AB  - OBJECTIVE: Previous studies have evaluated the association between miR-27a
      rs895819 polymorphism and cancer risk in Chinese population, but the results were
      inconclusive. The present meta-analysis was conducted to clarify these
      controversies. METHODS: A comprehensive search was conducted to identify all
      relevant case-control studies of miR-27a rs895819 polymorphism and cancer risk in
      Chinese participants. We calculated odds ratios (ORs) with 95% confidence
      intervals (CIs) to assess the strength of any association. RESULTS: A total of 12
      case-control studies involving 2655 cases and 3106 controls were included.
      Overall, the results suggested that there was no significant association between
      miR-27a rs895819 polymorphism and cancer risk in Chinese population (OR = 1.14,
      95%CI 0.86 to1.15, P = 0.85 for GG vs. AA). In the subgroup analysis by the
      source of controls, no significant association was found either among hospital
      based group (OR = 1.16, 95%CI 0.78 to 1.73) or population-based group (OR = 1.06,
      95%CI 0.74 to 1.35). However, when stratified by cancer types, we found a
      significant association between the polymorphism with colorectal cancer (OR =
      1.56, 95%CI 1.01 to 2.40 for GG vs. AA). CONCLUSION: miR-27a rs895819
      polymorphism was associated with increased risk of colorectal cancer in Chinese
      population.

PMID- 25976405
TI  - Combination of inflammation-related cytokines promotes long-term muscle stem cell
      expansion.
AB  - Muscle stem cells (MuSCs, satellite cells) are the major contributor to muscle
      regeneration. Like most adult stem cells, long-term expansion of MuSCs in vitro
      is difficult. The in vivo muscle regeneration abilities of MuSCs are quickly lost
      after culturing in vitro, which prevents the potential applications of MuSCs in
      cell-based therapies. Here, we establish a system to serially expand MuSCs in
      vitro for over 20 passages by mimicking the endogenous microenvironment. We
      identified that the combination of four pro-inflammatory cytokines, IL-1alpha, IL
      13, TNF-alpha, and IFN-gamma, secreted by T cells was able to stimulate MuSC
      proliferation in vivo upon injury and promote serial expansion of MuSCs in vitro.
      The expanded MuSCs can replenish the endogenous stem cell pool and are capable of
      repairing multiple rounds of muscle injuries in vivo after a single
      transplantation. The establishment of the in vitro system provides us a powerful
      method to expand functional MuSCs to repair muscle injuries. 

PMID- 25976408
TI  - Characterization of Bovine Serum Albumin Blocking Efficiency on Epoxy
      Functionalized Substrates for Microarray Applications.
AB  - Microarrays provide a platform for high-throughput characterization of
      biomolecular interactions. To increase the sensitivity and specificity of
      microarrays, surface blocking is required to minimize the nonspecific
      interactions between analytes and unprinted yet functionalized surfaces. To block
      amine- or epoxy-functionalized substrates, bovine serum albumin (BSA) is one of
      the most commonly used blocking reagents because it is cheap and easy to use.
      Based on standard protocols from microarray manufactories, a BSA concentration of
      1% (10 mg/mL or 200 MUM) and reaction time of at least 30 min are required to
      efficiently block epoxy-coated slides. In this paper, we used both fluorescent
      and label-free methods to characterize the BSA blocking efficiency on epoxy
      functionalized substrates. The blocking efficiency of BSA was characterized using
      a fluorescent scanner and a label-free oblique-incidence reflectivity difference
      (OI-RD) microscope. We found that (1) a BSA concentration of 0.05% (0.5 mg/mL or
      10 MUM) could give a blocking efficiency of 98%, and (2) the BSA blocking step
      took only about 5 min to be complete. Also, from real-time and in situ
      measurements, we were able to calculate the conformational properties (thickness,
      mass density, and number density) of BSA molecules deposited on the epoxy
      surface. 

PMID- 25976407
TI  - Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons
      from oxygen-glucose deprivation-induced necroptosis.
AB  - Necroptosis has an important role in ischemia-reperfusion damage. The expression
      of histone deacetylase 6 (HDAC6) is upregulated in neurons following ischemia
      reperfusion, however, whether HDAC6 is closely involved in the necroptosis, which
      occurs during ischemia-reperfusion damage remains to be elucidated. In the
      present study, the roles of HDAC6 in the necroptosis of cultured rat cortical
      neurons were investigated in a oxygen-glucose deprivation (OGD) model. The
      results demonstrated that OGD induced marked necroptosis of cultured rat cortical
      neurons and upregulated the expression of HDAC6 in the cultured neurons, compared
      with the control (P<0.05). The necroptosis inhibitor, necrostatin-1 (Nec-1),
      decreased The expression of HDAC6 in the OGD-treated cultured neurons,
      accompanied by the inhibition of necroptosis. Further investigation revealed
      that, compared with OGD treatment alone, inhibiting the activity of HDAC6 with
      tubacin, a specific HDAC6 inhibitor, reduced the OGD-induced necroptosis of the
      cultured rat cortical neurons (P<0.05), which was similar to the change following
      treatment with Nec-1 (P>0.05). In addition, inhibiting the activity of HDAC6
      reversed the OGD-induced increase of reactive oxygen species (ROS) and the OGD
      induced decrease of acetylated tubulin in the cultured rat cortical neurons
      (P<0.05), compared with the neurons treated with OGD alone). The levels of
      acetylated tubulin in the cultured neurons following treatment with OGD and
      tubacin were significantly higher than those in the control (P<0.05). These
      results suggested that HDAC6 was involved in the necroptosis of neurons during
      ischemia-reperfusion by modulating the levels of ROS and acetylated tubulin.

PMID- 25976409
TI  - Amplitude-spectral area and chest compression release velocity independently
      predict hospital discharge and good neurological outcome in ventricular
      fibrillation out-of-hospital cardiac arrest.
AB  - OBJECTIVE: In out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation
      (VF) the frequency-based waveform characteristic, amplitude-spectral area (AMSA)
      is associated with hospital discharge and good neurological outcome, yet AMSA is
      also known to increase in response to chest compressions (CC). In addition to
      rate and depth, well performed CC provides good chest recoil without leaning,
      reflected in the release velocity (RV). We hypothesized that AMSA is associated
      with hospital discharge and good neurological outcome independent of CC quality.
      METHODS: OHCA patients (age >= 18), with initial rhythm of VF from an Utstein
      Style database were analyzed. AMSA was measured prior to each shock, and averaged
      for each subject (AMSA-avg). Primary endpoint was hospital discharge and
      secondary endpoint was a good neurological outcome. Univariate and stepwise
      multivariable logistic regression, and receiver-operator-characteristic (ROC)
      analyses were performed. Factors analyzed were age, sex, witnessed status, time
      from dispatch to monitor/defibrillator application, number of shocks, first shock
      AMSA (AMSA1), AMSA-avg, averaged pre-shock pause, CC rate, depth, and RV.
      RESULTS: 140 subjects were analyzed. Hospital discharge was 31% and with good
      neurological outcome in 24% (77% of those discharged). AMSA-avg (p < 0.001), RV
      (p = 0.002), and age (p = 0.029) were independently associated with hospital
      discharge, with a non-significant trend for witnessed status (p = 0.069), with
      AUC = 0.846 for the multivariate model. For good neurological outcome, AMSA-avg
      (p = 0.001) and RV (p = 0.001) remained independently significant, with AUC =
      0.782. CONCLUSION: In OHCA with an initial rhythm of VF, AMSA-avg and CC RV are
      both highly and independently associated with hospital discharge and good
      neurological outcome.

PMID- 25976410
TI  - A radiographic comparison of human airway anatomy and airway manikins-
      Implications for manikin-based testing of artificial airways.
AB  - OBJECTIVE: The aim of this prospective, single-center, observational study was to
      investigate the accuracy of modeling and reproduction of human anatomical
      dimensions in manikins by comparing radiographic upper airway measurements of 13
      different models with humans. METHODS: 13 commonly used airway manikins (male or
      female anatomy based) and 47 controls (adult humans, 37 male, 10 female) were
      investigated using a mediosagittal and axial cervical spine CT scan. For
      anatomical comparison six human upper airway target structures, the following
      were measured: Oblique diameter of the tongue through the center, horizontal
      distance between the center point of the tongue and the posterior pharyngeal
      wall, horizontal distance between the vallecula and the posterior pharyngeal
      wall, distance of the upper oesophageal orifice length of epiglottis distance at
      the narrowest part of the trachea. Furthermore, the cross-section of the trachea
      in axial view and the cross-section of the upper oesophageal orifice in the same
      section was calculated. All measurements were compared gender specific, if the
      gender was non-specified with the whole sample. RESULTS: None of the included 13
      different airway manikins matched anatomy in human controls (n = 47) in all of
      the six measurements. The Laerdal Airway Management Trainer, however, replicated
      human airway anatomy at least satisfactorily. CONCLUSION: This investigation
      showed that all of the examined manikins did not replicate human anatomy.
      Manikins should therefore be selected cautiously, depending on the type of airway
      securing procedure. Their widespread use as a replacement for in vivo trials in
      the field of airway management needs to be reconsidered.

PMID- 25976411
TI  - Genetic dissection of the Mom5 modifier locus and evaluation of Mom5 candidate
      genes.
AB  - Germline mutations in the adenomatous polyposis coli (APC) gene cause familial
      adenomatous polyposis (FAP), a hereditary colon cancer syndrome in which affected
      individuals may develop 100-1000s of colonic adenomas. In families affected by
      FAP, adenoma number can vary markedly between individuals, despite the fact that
      these individuals carry the same APC mutation. In at least some FAP pedigrees,
      evidence suggests that these phenotypic differences are caused by segregating
      modifier alleles that impact adenoma number. However, identifying these modifiers
      in the human population is difficult, therefore mouse models are essential. Using
      the Apc (Min/+) mouse colon cancer model, we previously mapped one such modifier,
      Mom5, to a 25 Mbp region of chromosome 5 that contains hundreds of genes. The
      purpose of the present study was to refine the Mom5 interval and evaluate
      candidate genes for the Mom5 modifier of intestinal neoplasia. Recombinant mice
      were used to narrow the Mom5 interval to 8.1 Mbp containing 70 genes. In silico
      and gene expression analyses were utilized to identify and evaluate potential
      candidate genes that reside within this interval. These analyses identified seven
      genes within the Mom5 interval that contain variants between the B6 and 129P2
      strains. These genes represent the most likely candidates for the Mom5 modifier. 

PMID- 25976412
TI  - Prevalence and risk factors of intestinal protozoan and helminth infections among
      pulmonary tuberculosis patients without HIV infection in a rural county in P. R.
      China.
AB  - Although co-infection of tuberculosis (TB) and intestinal parasites, including
      protozoa and helminths, in humans has been widely studied globally, very little
      of this phenomenon is known in China. Therefore, a cross-sectional study was
      conducted in a rural county of China to investigate such co-infections. Patients
      with pulmonary TB (PTB) undergoing anti-Mycobacterium tuberculosis (anti-MTB)
      treatment were surveyed by questionnaires, and their feces and blood specimens
      were collected for detection of intestinal protozoa and helminths, routine blood
      examination and HIV detection. The chi(2) test and multivariate logistic
      regression model were used to identify risk factors. A total of 369 patients with
      PTB were included and all of them were HIV negative. Overall, only 7.3% of
      participants were infected with intestinal protozoa, among which prevalence of
      Blastocystis hominis, Entamoeba spp. and Trichomonas hominis were 6.0%, 1.1% and
      0.3%, respectively; 7.0% were infected with intestinal helminths, among which
      prevalence of hookworm, Trichuris trichiura, Ascaris lumbricoides and Clonorchis
      sinensis were 4.3%, 1.9%, 0.5% and 0.3%, respectively; and 0.5% were
      simultaneously infected with intestinal protozoa and helminths. Among patients
      with PTB, body mass index (BMI)<=18 (OR=3.30, 95% CI=1.44-7.54) and raised
      poultry or livestock (e.g., chicken, duck, pig) (OR=3.96, 95% CI=1.32-11.89) were
      significantly associated with harboring intestinal protozoan infection, while
      BMI<=18 (OR=3.32, 95% CI=1.39-7.91), anemia (OR=3.40, 95% CI=1.44-8.02) and
      laboring barefoot in farmlands (OR=4.54, 95% CI=1.88-10.92) were significantly
      associated with having intestinal helminth infection. Additionally, there was no
      significant relationship between duration of anti-MTB treatment and infection
      rates of intestinal parasites including protozoa and helminths. Therefore,
      preventing malnutrition, avoiding unprotected contact with reservoirs of
      protozoa, and improving health education for good hygiene habits, particularly
      wearing shoes while outdoors, are beneficial in the prevention of intestinal
      protozoan and helminth infection among patients with PTB. 

PMID- 25976413
TI  - Sequestration of host-CD59 as potential immune evasion strategy of Trichomonas
      vaginalis.
AB  - Trichomonas vaginalis is known to evade complement-mediated lysis. Because the
      genome of T. vaginalis does not possess DNA sequence with homology to human
      protectin (CD59), a complement lysis restricting factor, we tested the hypothesis
      that host CD59 acquisition by T. vaginalis organisms mediates resistance to
      complement killing. This hypothesis was based on the fact that trichomonads are
      known to associate with host proteins. No CD59 was detected on the surface of T.
      vaginalis grown in serum-based medium using as probe anti-CD59 monoclonal
      antibody (MAb). We, therefore, infected mice intraperitoneally with live T.
      vaginalis, and trichomonads harvested from ascites were tested for binding of
      CD59. Immunofluorescence showed that parasites had surface CD59. Furthermore, as
      mouse erythrocytes (RBCs) possess membrane-associated CD59, and trichomonads use
      RBCs as a nutrient source, organisms were co-cultured with murine RBCs for one
      week. Parasites were shown to have detectable surface CD59. Importantly, live T.
      vaginalis with bound CD59 were compared with batch-grown parasites without
      surface-associated CD59 for sensitivity to complement in human serum.
      Trichomonads without surface-bound CD59 had a higher level of killing by
      complement than did parasites with surface CD59. These data show that host CD59
      acquired onto the surface by live T. vaginalis may be an alternative mechanism
      for complement evasion. We describe a novel strategy by T. vaginalis consistent
      with host protein procurement by this parasite to evade the lytic action of
      complement. 

PMID- 25976414
TI  - Blastocystis and urticaria: Examination of subtypes and morphotypes in an unusual
      clinical manifestation.
AB  - Blastocystis is a human common enteric protist that may colonize a large variety
      of non-human hosts linked to symptoms and diseases such as abdominal pain,
      constipation, diarrhea, urticaria, flatulence and irritable bowel syndrome (IBS).
      Blastocystis exhibits remarkable genetic diversity and multiple subtypes (STs)
      within the genus with no absolute associations with clinical symptomatology. Here
      we analyzed fecal samples from Argentinean patients (n=270) belonging to
      symptomatic (urticaria and non-specific gastrointestinal symptoms, n=39) and
      asymptomatic control (n=28). Those patients infected with Blastocystis (n=67)
      were submitted for morphological analysis, DNA extraction, 18S PCR, sequencing
      and STs identification according to DNA barcoding. Blastocystis vacuolar forms
      were the predominant morphotype (75%), ameboid-like forms were evidenced in 1.5%
      of samples. Blastocystis ST3 was detected in 71.6% (n=48), of which 71.4%, (n=35)
      and 28.6% (n=14) belonged to symptomatic and asymptomatic respectively. Other
      subtypes identified were ST1 (14.9%), ST6 (7.5%) and ST2 (5.9%). Blastocystis 18S
      barcoding evidenced in non-urticaria symptomatic patients and asymptomatic
      control group the presence of allele 134 (ST3) (p<0.0001), while allele 34 (ST3)
      was detected in 85.7% (18/21) of symptomatic uricaria as compared with control
      group (1/21) (p<0.0001). The presence of a particular allele (a34) significantly
      associated with urticaria patients was detected and the clinical implications of
      these findings are herein discussed. 

PMID- 25976415
TI  - Invasion and persistence of Mycoplasma bovis in embryonic calf turbinate cells.
AB  - Mycoplasma bovis is a wall-less bacterium causing bovine mycoplasmosis, a disease
      showing a broad range of clinical manifestations in cattle. It leads to enormous
      economic losses to the beef and dairy industries. Antibiotic treatments are not
      efficacious and currently no efficient vaccine is available. Moreover, mechanisms
      of pathogenicity of this bacterium are not clear, as few virulence attributes are
      known. Microscopic observations of necropsy material suggest the possibility of
      an intracellular stage of M. bovis. We used a combination of a gentamicin
      protection assay, a variety of chemical treatments to block mycoplasmas entry in
      eukaryotic cells, and fluorescence and transmission electron microscopy to
      investigate the intracellular life of M. bovis in calf turbinate cells. Our
      findings indicate that M. bovis invades and persists in primary embryonic calf
      turbinate cells. Moreover, M. bovis can multiply within these cells. The
      intracellular phase of M. bovis may represent a protective niche for this
      pathogen and contribute to its escape from the host's immune defense as well as
      avoidance of antimicrobial agents. 

PMID- 25976418
TI  - Party Characteristics, Drinking Settings, and College Students' Risk of
      Intoxication: A Multi-Campus Study.
AB  - We examined party characteristics across different college drinking settings,
      associations between party characteristics and likelihood of drinking to
      intoxication, and the mediating role of perceived prevalence of intoxicated
      partygoers. Students (N = 6903) attending 14 public universities in California
      during the 2010 and 2011 fall semesters completed surveys on individual and party
      characteristics in six unique settings (e.g., residence hall). We used
      descriptive statistics to examine party characteristics by setting. We estimated
      multilevel logistic regression models to identify party characteristics
      associated with drinking to intoxication, and we used RMediation to determine
      significance of mediating effects. Individual and party characteristics varied by
      drinking context. Greater time at a party was associated with drinking to
      intoxication at five of six settings, while larger party size was significant
      only for outdoor settings. Enforcing the legal drinking age and refusing to serve
      intoxicated patrons were associated with lower likelihood of intoxication at
      Greek and off-campus parties. The presence of a keg was associated with drinking
      to intoxication at Greek, off-campus and outdoor parties; at bars, cover charges
      and drink promotions were positively associated with drinking to intoxication. In
      four of six settings, we found evidence of significant mediating effects through
      perceived prevalence of intoxicated partygoers. Findings highlight risk and
      protective characteristics of parties by drinking setting, and have prevention
      implications.

PMID- 25976419
TI  - Erratum. Protecting children from injury.

PMID- 25976416
TI  - Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk.
AB  - BACKGROUND: High body mass index (BMI) is consistently linked to increased risk
      of colorectal cancer for men, whereas the association is less clear for women. As
      risk estimates from observational studies may be biased and/or confounded, we
      conducted a Mendelian randomization study to estimate the causal association
      between BMI and colorectal cancer. METHODS: We used data from 10,226 colorectal
      cancer cases and 10,286 controls of European ancestry. The Mendelian
      randomization analysis used a weighted genetic risk score, derived from 77 genome
      wide association study-identified variants associated with higher BMI, as an
      instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR
      obtained using a conventional covariate-adjusted analysis. RESULTS: Individuals
      carrying greater numbers of BMI-increasing alleles had higher colorectal cancer
      risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our
      IV estimation results support the hypothesis that genetically influenced BMI is
      directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50;
      95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated
      with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95%
      CI, 1.26-2.61). For men, genetically influenced BMI was not associated with
      colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92). CONCLUSIONS:
      High BMI was associated with increased colorectal cancer risk for women. Whether
      abdominal obesity, rather than overall obesity, is a more important risk factor
      for men requires further investigation. IMPACT: Overall, conventional
      epidemiologic and Mendelian randomization studies suggest a strong association
      between obesity and the risk of colorectal cancer.

PMID- 25976420
TI  - Will Africa's future epidemic ride on forgotten lessons from the Ebola epidemic?
AB  - The Ebola virus disease (EVD) outbreak in the three West Africa countries of
      Guinea, Liberia, and Sierra Leone, was declared by the World Health Organization
      (WHO) as a public health event of international concern in August 2014. The
      disease, which has caused more than 10,000 deaths from over 25,000 cases, has
      thrived on a failed disease control system, national denial, and a poor and
      fragile healthcare delivery system. The slow and initially uncoordinated national
      and global response turned the outbreak into an unprecedented humanitarian
      disaster. Prevention and control of future outbreaks depend on improving and
      upgrading disease surveillance into a responsive component of a reliable and
      efficient health care delivery system. Appropriate capacity building with a
      conducive operating environment, which has been lacking in the past few decades,
      will be key to the health system strengthening. 

PMID- 25976417
TI  - Prediagnostic Physical Activity and Colorectal Cancer Survival: Overall and
      Stratified by Tumor Characteristics.
AB  - BACKGROUND: Physical activity is associated with a lower incidence of colorectal
      cancer; however, the relationship of physical activity with colorectal cancer
      survival is not yet clear. We evaluated the association between prediagnostic
      physical activity and colorectal cancer survival, overall and accounting for
      tumor markers associated with colorectal cancer survival: BRAF and KRAS mutation
      status and microsatellite instability (MSI) status. METHODS: Participants were 20
      to 74-year-old colorectal cancer patients diagnosed between 1998 and 2007 from
      the population-based Seattle Colon Cancer Family Registry (S-CCFR). Self-reported
      physical activity in the years preceding colorectal cancer diagnosis was
      summarized as average metabolic equivalent task hours per week (MET-h/wk; n =
      1,309). Somatic BRAF and KRAS mutations and MSI status were evaluated on a subset
      of patients (n = 1043). Cox regression was used to estimate HRs and 95%
      confidence intervals (CI) for overall and disease-specific survival after
      adjusting for relevant confounders. Stratified analyses were conducted across
      categories of BRAF, KRAS, and MSI, as well as tumor stage and site. RESULTS:
      Higher prediagnostic recreational physical activity was associated with
      significantly more favorable overall survival (HR for highest vs. lowest
      category, 0.70; 95% CI, 0.52-0.96); associations were similar for colorectal
      cancer-specific survival. Results consistently indicated a favorable association
      with physical activity across strata defined by tumor characteristics.
      CONCLUSION: Individuals who were physically active before colorectal cancer
      diagnosis experienced better survival than those who were inactive or minimally
      active. IMPACT: Our results support existing physical activity recommendations
      for colorectal cancer patients and suggest that the beneficial effect of activity
      is not specific to a particular molecular phenotype of colorectal cancer.

PMID- 25976422
TI  - Biological effect of hydrolyzed collagen on bone metabolism.
AB  - Osteoporosis is a chronic and asymptomatic disease characterized by low bone mass
      and skeletal microarchitectural deterioration, increased risk of fracture, and
      associated comorbidities most prevalent in the elderly. Due to an increasingly
      aging population, osteoporosis has become a major health issue requiring
      innovative disease management. Proteins are important for bone by providing
      building blocks and by exerting specific regulatory function. This is why
      adequate protein intake plays a considerable role in both bone development and
      bone maintenance. More specifically, since an increase in the overall metabolism
      of collagen can lead to severe dysfunctions and a more fragile bone matrix and
      because orally administered collagen can be digested in the gut, cross the
      intestinal barrier, enter the circulation, and become available for metabolic
      processes in the target tissues, one may speculate that a collagen-enriched diet
      provides benefits for the skeleton. Collagen-derived products such as gelatin or
      hydrolyzed collagen (HC) are well acknowledged for their safety from a
      nutritional point of view; however, what is their impact on bone biology? In this
      manuscript, we critically review the evidence from literature for an effect of HC
      on bone tissues in order to determine whether HC may represent a relevant
      alternative in the design of future nutritional approaches to manage osteoporosis
      prevention.

PMID- 25976421
TI  - Steroid hormones in prediction of normal pressure hydrocephalus.
AB  - Normal pressure hydrocephalus (NPH) is a treatable neurological disorder
      affecting elderly people with the prevalence increasing with age. NPH is caused
      by abnormal cerebrospinal fluid (CSF) reabsorption and manifested as a balance
      impairment, urinary incontinence and dementia development. These symptoms are
      potentially reversible if recognized early. Diagnosis of NPH is difficult and can
      be easily mistaken for other neurodegenerative disorders, which makes NPH one of
      the major misdiagnosed diseases worldwide. The aim of the study was to find out
      the appropriate combination of indicators, based on CSF steroids, which would
      contribute to a clearer NPH diagnosis. The levels of CSF cortisol, cortisone,
      dehydroepiandrosterone (DHEA), 7alpha-OH-DHEA, 7beta-OH-DHEA, 7-oxo-DHEA, 16alpha
      OH-DHEA and aldosterone (all LC-MS/MS) were determined in our patients (n=30;
      NPH, 65-80 years) and controls (n=10; 65-80 years). The model of orthogonal
      projections to latent structures (OPLS) was constructed to predict NPH.
      Cortisone, 7alpha-OH-DHEA, 7beta-OH-DHEA, 7-oxo-DHEA, aldosterone, 7alpha-OH-DHEA
      /DHEA, 7-oxo-DHEA/7alpha-OH-DHEA, 7beta-OH-DHEA/7-oxo-DHEA and 16alpha-OH
      DHEA/DHEA in the CSF were identified as the key predictors and the model
      discriminated patients from controls with 100% sensitivity and 100% specificity.
      The suggested model would contribute to early and accurate NPH diagnosis,
      enabling promptly treatment of the disease. 

PMID- 25976423
TI  - Breast cancer survivors' perceived medical communication competence and
      satisfaction with care at the end of treatment.
AB  - BACKGROUND: Information is a care priority in most breast cancer survivors (BCS).
      We assessed whether BCS information needs at 8 months after hospital cancer
      treatment could be related to their age, education level, perceived medical
      communication competence, satisfaction with care, attachment style, and self
      esteem. METHODS: Of 426 BCS approached during the last week of treatment (T1),
      85% completed the Medical Communication Competence Scale, European Organisation
      for Research and Treatment of Cancer Satisfaction with Care Questionnaire,
      Rosenberg's Self-Esteem Scale and Experiences in Close Relationships Scale. The
      Hospital Anxiety and Depression Scale and the Supportive Care Needs Survey were
      completed at T1 and again 8 months later (T2) with a 66% (n = 283) response rate.
      RESULTS: Baseline respondents' median (range) age was 56 years (23-86 years).
      Information needs decreased over time, although some persisted. Multivariate
      regression analyses evidenced overall higher information needs at T2 in younger
      BCS and in those dissatisfied with the information provided at T1. Specifically,
      in younger BCS, higher information needs were related to lower satisfaction with
      doctors' availability, and in older BCS, they were related to higher self
      perceived competence in information giving, lower self-perceived competence in
      information seeking, and lower satisfaction with doctors' information provision.
      Psychological distress was strongly related to information needs. Education, BCS
      attachment style, and self-esteem were not associated with information needs.
      CONCLUSIONS: In order to enhance supportive care for BCS, younger BCS should be
      provided with more time to address all their concerns and older BCS should be
      encouraged to express their specific desires for information.

PMID- 25976426
TI  - Risk and Prevalence of Anemia among Women Attending Public and Private
      Universities.
AB  - Anemia is a global public health problem. Women are known to be more susceptible
      to anemia; however, no controlled study has yet assessed differences in the
      prevalence of anemia exclusively among women with higher education. The aim of
      the study was to establish the prevalence of anemia among women attending
      universities. The hemoglobin concentration of 140 women aged 18 to 45 years old
      from a private and a public university was measured. Anthropometric and
      socioeconomic data were also collected. The risk of developing anemia was almost
      threefold higher among the students attending the public university (OR: 2.71;
      p=.0248). The prevalence of anemia was much higher than in the overall female
      population (79%). The higher education was not a protective factor for anemia in
      women when analysed separately from the total population of women.

PMID- 25976424
TI  - Evidence for Changes in Numbers of Synaptic Inputs onto KNDy and GnRH Neurones
      during the Preovulatory LH Surge in the Ewe.
AB  - Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA)
      are critical mediators of gonadal steroid feedback onto gonadotrophin-releasing
      hormone (GnRH) neurones. ARC kisspeptin cells that co-localise neurokinin B (NKB)
      and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn)
      neurones, and have been shown in mice to also co-express the vesicular glutamate
      transporter, vGlut2, an established glutamatergic marker. The ARC in rodents has
      long been known as a site of hormone-induced neuroplasticity, and changes in
      synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based
      on this evidence, the the present study aimed to examine possible changes across
      the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC
      (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season
      ewes were perfused using 4% paraformaldehyde during either the luteal or
      follicular phase of the oestrous cycle, with the latter group killed at the time
      of the luteinising hormone (LH) surge. Hypothalamic sections were processed for
      triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or
      kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive
      inputs to ARC KNDy neurones were significantly increased at the time of the LH
      surge compared to the luteal phase; because these did not contain kisspeptin,
      they do not arise from KNDy neurones. By contrast to the ARC, the total number of
      synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between
      luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs
      onto GnRH neurones in the mediobasal hypothalamus (MBH) was also increased during
      the LH surge, and could be attributed to an increase in the number of KNDy
      (double-labelled kisspeptin + vGlut2) inputs. Taken together, these results
      provide novel evidence of synaptic plasticity at the level of inputs onto KNDy
      and GnRH neurones during the ovine oestrous cycle. Such changes may contribute to
      the generation of the preovulatory GnRH/LH surge. 

PMID- 25976425
TI  - How Did Multiple FDA Actions Affect the Utilization and Reimbursed Costs of
      Thiazolidinediones in US Medicaid?
AB  - PURPOSE: The US Food and Drug Administration (FDA) communicated the potential
      cardiovascular risk of thiazolidinediones (rosiglitazone and pioglitazone) in
      2007 and required a Risk Evaluation and Mitigation Strategy (REMS) for
      rosiglitazone in 2010. It also communicated in 2010 the potential risk of bladder
      cancer with pioglitazone use. This study examined the effects of these multiple
      FDA actions on utilization and reimbursed costs of thiazolidinediones in state
      Medicaid programs. METHODS: State Drug Utilization Data from the Centers for
      Medicare & Medicaid Services were assessed. An interrupted time series design and
      segmented linear regression models were used to examine changes in market shares
      according to both prescription volume and reimbursed costs for rosiglitazone and
      pioglitazone in the Northeast and Midwest regions of the United States after
      multiple FDA actions. FINDINGS: Compared with expected rates, there were relative
      reductions of 65.84% (Northeast region) and 55.09% (Midwest region) in the use of
      rosiglitazone at 1 year after the 2007 FDA actions for thiazolidinediones and
      cardiac risk. At the same time, relative increases of 7.30% and 9.28% in the use
      of pioglitazone were observed in the Northeast and Midwest regions, respectively.
      Changes in both use and costs of rosiglitazone after the 2010 REMS program could
      not be estimated because of the already low rates (~1%) before REMS was
      implemented. One year after the 2010 FDA actions for pioglitazone and its
      possible association with bladder cancer, relative reductions in pioglitazone use
      of 21.41% (Northeast region) and 18.12% (Midwest region) were detected.
      IMPLICATIONS: The Northeast and Midwest regions reported similar patterns of
      changes after the FDA actions. Use and costs of rosiglitazone were substantially
      reduced after the 2007 FDA actions for cardiovascular risk, and this drug was
      rarely used after the 2010 REMS program. Conversely, use and costs of
      pioglitazone were substantially reduced after the 2010 FDA actions regarding the
      drug's possible risk of bladder cancer.

PMID- 25976427
TI  - Toxicological effects of pet food ingredients on canine bone marrow-derived
      mesenchymal stem cells and enterocyte-like cells.
AB  - We developed an in vitro method to assess pet food ingredients safety. Canine
      bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into
      enterocyte-like cells (ELC) to assess toxicity in cells representing similar
      patterns of exposure in vivo. The toxicological profile of clove leave oil,
      eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose,
      ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and
      citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine
      monophosphate was 59.42 +/- 0.90 and 56.7 +/- 3.5 mg ml(-1) for BMSC and ELC;
      56.84 +/- 0.95 and 53.66 +/- 1.36 mg ml(-1) for GMP; 0.02 +/- 0.001 and 1.25 +/-
      0.47 mg ml(-1) for citric acid; 0.077 +/- 0.002 and 0.037 +/- 0.01 mg ml(-1) for
      cinnamaldehyde; 0.002 +/- 0.0001 and 0.002 +/- 0.0008 mg ml(-1) for thymol; 0.080
      +/- 0.003 and 0.059 +/- 0.001 mg ml(-1) for thyme oil; 0.111 +/- 0.002 and 0.054
      +/- 0.01 mg ml(-1) for cinnamon bark oil; 0.119 +/- 0.0004 and 0.099 +/- 0.011 mg
      ml(-1) for clove leave oil; 0.04 +/- 0.001 and 0.028 +/- 0.002 mg ml(-1) for
      eugenol; 2.80 +/- 0.11 and 1.75 +/- 0.51 mg ml(-1) for ginger root extract; > 200
      and 116.78 +/- 7.35 mg ml(-1) for sorbose. Lemon grass oil was evaluated at 0.003
      0.9 in BMSC and .03-0.9 mg ml(-1) in ELC and its mechanistic effect was
      investigated. The gene toxicology studies showed regulation of 61% genes in
      CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC.
      For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for
      mitochondrial energy metabolism. In conclusion, these studies provide a baseline
      against which differential toxicity of dietary feed ingredients can be assessed
      in vitro for direct effects on canine cells and demonstrate differential toxicity
      in differentiated cells that represent gastrointestinal epithelial cells.

PMID- 25976428
TI  - Efficacy of chemotherapy in epidermal growth factor receptor (EGFR) mutated
      metastatic pulmonary adenocarcinoma patients who had acquired resistance to first
      line EGFR tyrosine kinase inhibitor (TKI).
AB  - INTRODUCTION: Salvage chemotherapy is frequently used when tumour epidermal
      growth factor receptor (EGFR) mutated patients experience disease progression
      with first-line EGFR-tyrosine kinase inhibitor (TKI) treatment. However, the
      efficacy of salvage chemotherapy is still unknown. METHODS: We retrospectively
      reviewed the chart records of our pulmonary adenocarcinoma patients between 2010
      and 2013. RESULTS: Five hundred and six of the 1240 stage IV adenocarcinoma
      patients had an EGFR mutation and 338 received first-line EGFR-TKI treatment. In
      all, 169 patients in this group received salvage chemotherapy after failure of
      EGFR-TKI, and 102 patients were eligible for this study. The chemotherapy
      response rate of these 102 patients was 24.5%, with a median progression-free
      survival (PFS) of 4.5?months, and median survival time was 14.6?months. Patients
      who received pemetrexed-based chemotherapy had longer PFS and overall survival
      (OS), although the extent was statistically insignificant. Progression-free
      survival and OS were longer for patients who received combination chemotherapy
      than single-agent chemotherapy. CONCLUSIONS: Pemetrexed-based combination
      chemotherapy is preferred before a more efficient treatment strategy is found.

PMID- 25976429
TI  - HLA-B*38:55Q: a new alternatively expressed allele identified in a three
      generation Italian family.
AB  - The new allelic variant HLA-B*38:55Q differs from the closest related B*38:01:01
      by one nucleotide substitution at position 373 in exon 3 (TGC>CGC). This results
      in a difference of one amino acid at residue 101 of the HLA-B heavy chain, from a
      neutral-polar Cys to a basic-polar Arg, thus impairing disulphide bridge
      formation in the alpha-2 domain. This alteration of the secondary structure
      probably affects the maturation of the heavy chain and the level of surface
      expression, making the HLA-B*38:55Q undetectable by standard serological typing. 

PMID- 25976430
TI  - Maternal, fetal, and placental conditions associated with medically indicated
      late preterm and early term delivery: a retrospective study.
AB  - OBJECTIVE: Our objectives were: (1) to examine the association between maternal,
      fetal, and placental phenotypes of preterm delivery and medically indicated early
      delivery of singletons during the late preterm and early term periods; and (2) to
      identify the specific maternal, fetal, and placental conditions associated with
      these early deliveries. DESIGN: Retrospective study. SETTING: City of London and
      Middlesex County, Ontario, Canada. SAMPLE: Singleton live deliveries, at 34-41
      weeks of gestation to women in London and Middlesex. METHODS: We obtained data
      from a city-wide perinatal database (2002-2011; n = 25 699). We used multinomial
      logistic regression for multivariable analyses. MAIN OUTCOME MEASURE: The outcome
      was the occurrence of medically indicated late preterm (34-36 weeks of gestation)
      and early term (37-38 weeks of gestation) delivery, versus delivery at full term
      (39-41 weeks of gestation). RESULTS: After controlling for confounding factors,
      all phenotypes were associated with increased odds of medically indicated late
      preterm and early term delivery. Within the maternal phenotype, chronic maternal
      medical conditions were associated with increased odds of medically indicated
      early term delivery (e.g. for gastrointestinal disease, adjusted odds ratio, aOR
      1.72, 95% CI 1.47-2.00; for anaemia, aOR 1.40, 95% CI 1.20-1.63), but not late
      preterm delivery. CONCLUSIONS: The aetiology of medically indicated early
      delivery close to full term is heterogeneous. Patterns of associations suggest
      slightly different conditions underlying the late preterm and early term
      phenotypes, with chronic maternal medical conditions being associated with early
      term delivery but not with late preterm delivery. These results have implications
      for the prevention of early delivery as well as the identification of high-risk
      groups among those born early. TWEETABLE ABSTRACT: The aetiology of medically
      indicated late preterm and early term delivery is heterogeneous.

PMID- 25976431
TI  - The workflow from post-mortem human brain sampling to cell microdissection: a
      Brain Net Europe study.
AB  - Brain banks manage and store fully clinically and pathologically characterised
      brains. The diversity of techniques used in research projects increases. These
      biological resource centres are made to adapt brain tissue processing.
      Furthermore, the development of more sensitive techniques to analyse nucleic
      acids and proteins offers new fields of exploration when combined with laser
      capture microdissection in order to decipher the physiopathology of diseases at
      the cell level. In this study, our goal was to evaluate procedures and set a
      workflow compatible with the constraints of brain banks, from brain sampling to
      laser capture microdissection and pre-analytical quality assessment. We compared
      various methods of freezing brain tissue, focused on morphological quality
      preservation of brain microscopical structures and on the quality of nucleic acid
      or protein yields. Staining protocols combined with strategies to lower neurones
      autofluorescence were adapted for the same purpose. Finally, we found that laser
      capture microdissection is possible in the setting of brain banks. However, the
      entire process has to be envisioned from the autopsy to the analysis. The impact
      on protein or nucleic acid quality is a limitation that restricts the amount of
      samples available for this purpose. 

PMID- 25976433
TI  - Disorders for which the allergist-immunologist is particularly well-qualified to
      treat.

PMID- 25976434
TI  - Food protein-induced enterocolitis syndrome and allergic proctocolitis.
AB  - Non-IgE-mediated food allergic disorders account for up to 40% of milk protein
      allergy in infants and young children. We aim to review the recent literature and
      to provide an update on diagnosis and management of food protein-induced
      enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis
      (FPIAP). The peer-reviewed articles indexed in PubMed have been reviewed. FPIES
      manifests in infants as profuse, repetitive vomiting and lethargy, often with
      diarrhea, leading to acute dehydration, or weight loss and failure to thrive, in
      chronic form. FPIES is caused most commonly by cow's milk (CM) and soy proteins;
      rice, oat, and other solid foods may also trigger FPIES. FPIES rarely occurs in
      the exclusively breastfed infants. FPIES is underrecognized; children are often
      mismanaged as having acute viral gastrointestinal illness, sepsis, or surgical
      disease, delaying diagnosis of FPIES for many months. Approximately 25% of
      children with FPIES develop food-specific IgE antibodies and some transition to
      immediate food allergy; IgE positivity is associated with a more protracted
      course. FPIES is a self-limiting condition, with most cases resolving by age
      three to five years. Ondansetron may be helpful in managing acute FPIES. FPIAP is
      a benign condition of bloody stools in a well-appearing infant, with usual onset
      between one and four weeks of age. Up to 60% of cases occur in exclusively
      breastfed infants and resolve with maternal elimination of CM and soy proteins.
      The majority of cases resolve by age 12 months. FPIES may transition to IgE
      mediated food allergy in some patients; IgE positivity to the FPIES food is a
      marker of a more persistent disease. FPIAP is benign and resolves by age 12
      months in most patients. 

PMID- 25976432
TI  - Neuropathobiology of non-motor symptoms in Parkinson disease.
AB  - Parkinson disease (PD) is a multisystem disorder associated with alpha-synuclein
      aggregates throughout the central, autonomic, and peripheral nervous system,
      clinically characterized by motor and non-motor (NM) symptoms. The NMS in PD,
      many of which antedating motor dysfunction and representing a preclinical phase
      spanning 20 or more years, are linked to widespread distribution of alpha
      synuclein pathology not restricted to the dopaminergic nigrostriatal system that
      is responsible for core motor features of PD. The pathologic substrate of NM
      manifestations such as olfactory, autonomic (gastrointestinal, urogenital,
      cardia, respiratory), sensory, skin, sleep, visual, neuropsychiatric dysfunctions
      (cognitive, mood, dementia), and others are critically reviewed. In addition to
      non-nigral brainstem nuclei, alpha-synuclein pathology involves sympathetic and
      parasympathetic, enteric, cardiac and pelvic plexuses, and many other organs
      indicating a topographical and chronological spread, particularly in the
      prodromal stages of the disease. Few animal models recapitulate NMS in PD. The
      relationship between regional alpha-synuclein/Lewy pathology, neurodegeneration
      and the corresponding clinical deficits awaits further elucidation. Controlled
      clinicopathologic studies will refine the correlations between presymptomatic and
      late-developing NM features of PD and neuropathology, and new premotor biomarkers
      will facilitate early diagnosis of PD as a basis for more effective preventive
      and therapeutic options of this devastating disease. 

PMID- 25976435
TI  - Effect of chemical modifications on allergenic potency of peanut proteins.
AB  - BACKGROUND: Modification of native peanut extracts could reduce adverse effects
      of peanut immunotherapy. OBJECTIVE: We sought to compare native and chemically
      modified crude peanut extract (CPE) and major peanut allergens Ara h 2 and Ara h
      6 in a mediator-release assay based on the rat basophilic leukemia (RBL) cell
      line transfected with human Fcepsilon receptor. METHODS: Native Ara h 2/6 was
      reduced and alkylated (RA), with or without additional glutaraldehyde treatment
      (RAGA). CPE was reduced and alkylated. Sera of subjects with peanut allergy (16
      males; median age 7 years) were used for overnight RBL-passive sensitization.
      Cells were stimulated with 0.1 pg/mL to 10 MUg/mL of peanut. beta-N
      acetylhexosaminidase release (NHR) was used as a marker of RBL degranulation,
      expressed as a percentage of total degranulation caused by Triton X. RESULTS:
      Median peanut-specific immunoglobulin E was 233 kUA/L. Nineteen subjects were
      responders, NHR >= 10% in the mediator release assay. Responders had reduced NHR
      by RA and RAGA compared with the native Ara h 2/6. Modification resulted in a
      later onset of activation by 10- to 100-fold in concentration and a lowering of
      the maximum release. Modified RA-Ara h 2/6 and RAGA-Ara h 2/6 caused
      significantly lower maximum mediator release than native Ara h 2/6, at protein
      concentrations 0.1, 1, and 10 ng/mL (p < 0.001, < 0.001, and < 0.001,
      respectively, for RA; and < 0.001, 0.026, and 0.041, respectively, for RAGA). RA
      CPE caused significantly lower maximum NHR than native CPE, at protein
      concentration 1 ng/mL (p < 0.001) and 10 ng/mL (p < 0.002). Responders had high
      rAra h 2 immunoglobulin E (mean, 61.1 kUA/L; p < 0.001) and higher NHR in
      mediator release assay to native Ara h 2/6 than CPE, which indicates that Ara h
      2/6 were the most relevant peanut allergens in these responders. CONCLUSIONS:
      Chemical modification of purified native Ara h 2 and Ara h 6 reduced mediator
      release in an in vitro assay ~100-fold, which indicates decreased allergenicity
      for further development of the alternative candidate for safe peanut
      immunotherapy.

PMID- 25976436
TI  - IgE reactivity to carbohydrate moieties of glycoproteins in wheat allergy.
AB  - Carbohydrate moieties of different glycoproteins, such as cross-reactive
      carbohydrate determinants (CCDs) and galactose alpha-1,3-galactose, can induce
      IgE reactivity with varied clinical significance. In this study, the possible
      participation of glycan from wheat gliadin, with respect to its IgE-binding
      capacity, was investigated in children with food allergies to wheat. Total IgE
      and wheat-specific IgE quantification, documentation of history, and/or oral food
      challenge (OFC) were performed for 52 children. Subjects with positive wheat
      specific IgE were characterized as the symptomatic group, never-exposed group, or
      asymptomatic group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and glycan detection in gliadin were performed. IgE binding to gliadin
      and deglycosylated gliadin was measured by immunoblotting and ELISA. Gliadin
      specific IgE was detected and correlated with wheat-specific IgE in the
      symptomatic, never-exposed, and asymptomatic groups. The glycan range overlapped
      significantly with the gliadin range. Deglycosylation of gliadin reduced the
      allergenicity of gliadin. In gliadin, the allergenicity of the glycan portion was
      greater in the symptomatic group than in the never-exposed and asymptomatic
      groups. We conclude that N-glycan in gliadin might exhibit allergenicity as a
      possible carbohydrate epitope in wheat allergy in children. 

PMID- 25976437
TI  - Stepping down from inhaled corticosteroids with leukotriene inhibitors in asthma:
      a systematic review and meta-analysis.
AB  - BACKGROUND: The risks of using leukotriene receptor antagonists (LTRA) as part of
      a strategy for stepping down inhaled corticosteroid (ICS) are not well known.
      OBJECTIVE: To estimate the risk of asthma exacerbation in individuals with stable
      asthma who start LTRA when stopping ICS or reducing ICS dose. METHODS: We
      identified articles from a systematic review of English and non-English articles
      by using a number of data bases. We included randomized controlled trials with a
      stable asthma run-in period of 4 weeks or more and a follow-up period of at least
      3 months. We included studies of individuals with stable asthma who stopped ICS
      and substituted LTRA (versus continuing ICS) and who reduced ICS while starting
      LTRA (versus placebo). RESULTS: The search strategy identified 1132 potential
      articles, of which 52 were reviewed at the full-text level, and four met criteria
      for inclusion. The single article that met the inclusion criteria for
      substitution of LTRA for ICS as a step-down strategy found a statistically
      increased risk of treatment failure of 30.3% for substituting LTRA compared with
      20.2% for continuing ICS. The three articles that met the inclusion criteria for
      comparing LTRA versus placebo in patients with stable asthma who reduce ICS found
      a modestly decreased risk ratio that favored LTRA of 0.57 (95% confidence
      interval, 0.36-0.90; I(2) = 0%) in studies that only included individuals >15
      years old. CONCLUSION: Only one study addressed the risk of substitution of LTRA
      for ICS in stable asthma, which limited any strong conclusions about this step
      down strategy.

PMID- 25976438
TI  - Current state of hereditary angioedema management: a patient survey.
AB  - Hereditary angioedema (HAE) is a chronic disease with a high burden of disease
      that is poorly understood and often misdiagnosed. Availability of treatments,
      including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant,
      marks a significant advance for HAE patients. We aimed to better understand the
      current state of HAE care, from a patient perspective, after the introduction of
      several novel therapies. One session of the United States Hereditary Angioedema
      Association 2013 patient summit was devoted to data collection for this study.
      Patients attending the summit were self-selected, and HAE diagnosis was self
      reported. Survey questions assessed patient characteristics, burden of disease,
      and treatment. Participant responses were captured using an audience response
      system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with
      normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients
      (76%) equally reported that HAE had a significant impact on quality of life
      (QOL). A third of HAE-C1INH patients were diagnosed within one year of their
      first HAE attack, but another third reported a delay of more than 10 years. Most
      HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available.
      HAE-C1INH patients frequently had an individual treatment plan (76%) compared
      with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency
      department (ED) or were hospitalized less than once every six months (80%). Our
      findings show that HAE management is improving with good access to on-demand and
      prophylactic treatment options. However, HAE patients still have a significant
      burden of disease and continued research and educational efforts are needed. 

PMID- 25976439
TI  - Selective IgE deficiency and cardiovascular diseases.
AB  - Selective immunoglobulin E (IgE) deficiency (IgED) is defined as serum levels of
      IgE more than or equal to 2 kIU/L and is associated with immune dysregulation and
      autoimmunity. This study aimed to investigate a prevalence of atherosclerotic
      cardiovascular disease (ASCVD) in population with IgED. Within the electronic
      patient record (EPR) database of Leumit Health Care Services (LHS) in Israel,
      data capture was performed using IBM Cognos 10.1.1 BI Report Studio software. The
      case samples were drawn from the full study population (n = 18,487), having any
      allergy-related symptoms and/or those requesting antiallergy medications and
      performed serum total IgE measurement during 2012 at LHS. All subjects aged more
      than or equal to 40 years old, with serum total IgE less than 2 kIU/L were
      included in case group. Control group was randomly sampled from the remained
      subjects, with a case-control ratio of 10 controls for each case (1:10). The
      comorbid cardiovascular diseases during less than or equal to 10 years before
      serum total IgE testing were identified and retrieved using specific
      International Classification of Diseases, 9th Revision, Clinical Modification
      diagnostic codes. There were 103 in case and 1030 subjects in control group.
      Compared with control group patients, the case group had significantly more
      arterial hypertension [34 (37.7%) versus 187 (18.2%), p < 0.001], ischemic heart
      disease (IHD) [26 (25.2%) versus 87 (8.4%), p < 0.001], carotid stenosis [5
      (4.9%) versus 7 (0.7%), p = 0.003], cerebrovascular disease (CVD) [3 (2.9%)
      versus 5 (0.5%), p = 0.029], and peripheral vascular disease (PVD) [4 (3.9%)
      versus 9 (0.9%), p = 0.024]. IgED is associated with higher prevalence of
      arterial hypertension and ASCVD. 

PMID- 25976440
TI  - A 60-year-old woman with recurrent episodes of flushing, urticaria, and
      angioedema.
AB  - Recurrent episodes of flushing, urticaria, and angioedema raise suspicion for
      many conditions with a wide differential diagnosis. The diagnostic approach
      involves consideration of allergic, cardiovascular, gastrointestinal, endocrine,
      infectious, neurologic, dermatologic, and drug-related causes. We describe a
      unique case of recurrent episodes of flushing, urticaria, and angioedema that has
      gone into remission after a novel therapeutic intervention. 

PMID- 25976441
TI  - Role of vitamin D3 in atopic dermatitis and immunity: some comments.

PMID- 25976442
TI  - Role of vitamin D3 in atopic dermatitis and immunity: some comments--reply.

PMID- 25976443
TI  - For the patient.

PMID- 25976444
TI  - Enzyme-activated intracellular drug delivery with tubule clay nanoformulation.
AB  - Fabrication of stimuli-triggered drug delivery vehicle s is an important
      milestone in treating cancer. Here we demonstrate the selective anticancer drug
      delivery into human cells with biocompatible 50-nm diameter halloysite nanotube
      carriers. Physically-adsorbed dextrin end stoppers secure the intercellular
      release of brilliant green. Drug-loaded nanotubes penetrate through the cellular
      membranes and their uptake efficiency depends on the cells growth rate.
      Intercellular glycosyl hydrolases-mediated decomposition of the dextrin tube-end
      stoppers triggers the release of the lumen-loaded brilliant green, which allowed
      for preferable elimination of human lung carcinoma cells (A549) as compared with
      hepatoma cells (Hep3b). The enzyme-activated intracellular delivery of brilliant
      green using dextrin-coated halloysite nanotubes is a promising platform for
      anticancer treatment. 

PMID- 25976446
TI  - [Lead-in period and week 8 as predictive tools for response to boceprevir
      therapy: a retrospective study of Spanish real clinical practice].
AB  - INTRODUCTION: Most discontinuations due to lack of virological response occur
      during the first few weeks of hepatitis C virus (HCV) triple therapy. Improved
      knowledge of baseline factors and their correlation with boceprevir decision
      points may predict treatment success. METHODS: An observational, retrospective
      study was conducted to describe the lead-in period as a clinical decision tool in
      HCV genotype 1 patients treated with boceprevir. Data were collected from the
      medical records of 186 consecutive patients distributed across 20 Spanish general
      hospitals. RESULTS: This study included 171 patients. A total of 80% had fibrosis
      F3/F4, 74% were previously treated, and 26% were treatment-naive. After the lead
      in period, 54.5% of the patients had a reduction of >=1 log10; this reduction
      occurred in 52.5% of those with advanced fibrosis. Boceprevir therapy was started
      in 94% of the patients. Discontinuations at week 4 were limited to null
      responders with cirrhosis. The baseline factors associated with virological
      response at week 4 were IL28B, previous response, and fibrosis score. At week 8,
      HCV-RNA was undetectable in 48.8% of the patients. The correlation between
      responses at weeks 8 and 12 was 88%. CONCLUSION: In the Spanish clinical setting,
      lead-in was mainly used as a clinical decision point for non-responders with
      cirrhosis. The good correlation between stopping rules at weeks 8 and 12 could be
      used to anticipate discontinuation, thus saving adverse events and costs.

PMID- 25976447
TI  - Descriptive analysis of tumor cells with stem like phenotypes in metastatic and
      benign adrenal tumors.
AB  - BACKGROUND: Neuroblastoma (NB) comprises 7% of all childhood cancers. Here we
      report a descriptive analysis of key cellular markers that have "stem-like"
      properties which theoretically represents the self-renewing population of cells
      responsible for generating new tumor cells. Samples are obtained from freshly
      isolated tissue from nonmetastatic NB, metastatic NB, benign adrenal adenoma and
      a ganglioneuroma. In addition, in metastatic NB, descriptive analysis of the
      tumor cells after 3D culture as well as reanalysis of fresh tumor obtained after
      surgical excision posttreatment was performed. METHODS: Cells were isolated from
      primary tissue and characterized via immunohistochemistry and flow cytometry for
      markers associated with stem-like properties. In two patients, reanalysis was
      performed in freshly isolated tissue after chemotherapy. In three patients,
      freshly isolated tumors were cultured in 3 dimensions for 7-10 days and changes
      in stem-like marker expression were characterized. RESULTS: Flow analysis of
      metastatic NB revealed elevated levels of markers CD133, CD24, CD44, Oct4, CXCR4
      and Nestin. In addition, some markers such as CD133 and CXCR4 maintained
      increased expression after chemotherapy. CONCLUSIONS: The expression profile of
      cells with "stem-like" properties has individual variability and differs
      depending on the tumor type. In metastatic NB, expression of "stem-like" markers
      Nestin, Oct4, and CXCR4 are maintained in a higher percentage of cells and this
      persists even after chemotherapy. In addition, culture of freshly isolated tissue
      maintained the individual expression profile of stem-like markers for at least 7
      days.

PMID- 25976445
TI  - Geriatric assessment as predictors of hospital readmission in older adults with
      cancer.
AB  - BACKGROUND: Hospital readmission is a common, costly problem. Little is known
      regarding risk factors for readmission in older adults with cancer. This study
      aims to identify factors associated with 30-day readmission in a cohort of older
      medical oncology patients. SETTING/PARTICIPANTS: Adults age 65 and over
      hospitalized to an Oncology Acute Care for Elders Unit at Barnes-Jewish Hospital.
      MEASUREMENTS: Standard geriatric screening tests were administered in routine
      clinical care. Clinical data and 30-day readmission status were obtained through
      medical record review. RESULTS: 677 patients met the inclusion criteria. 77% were
      white and 53% were male. Thoracic (32%), hematologic (20%), and gastrointestinal
      (18%) malignancies were most common. The 30-day unplanned readmission rate was
      35.2%. Multivariable analyses identified complete dependence in feeding (odds
      ratio [OR], 3.70; 95% confidence interval [CI], 1.29-10.65), and some dependence
      (1.58, 1.04-2.41) and complete dependence (2.64, 1.70-4.12) in housekeeping,
      prior to admission, as associated with higher odds of readmission. Age<75 (1.49,
      1.04-2.14), African-American race (1.59, 1.06-2.39), potentially inappropriate
      medications (1.36, 0.94-1.99), and higher-risk reasons for index admission (1.93,
      1.34-2.78) also increased odds of readmission. These factors were organized into
      a prognostic index. CONCLUSION: Hospital readmission was common and higher than
      previously reported rates in general medical populations. We identified several
      previously unrecognized factors associated with increased risk for readmission,
      including some geriatric assessment parameters, and developed a practical tool
      that can be used by clinicians to assess risk of 30-day readmission.

PMID- 25976448
TI  - The impact of therapeutic hypothermia on on-treatment platelet reactivity and
      clinical outcome in cardiogenic shock patients undergoing primary PCI for acute
      myocardial infarction: Results from the ISAR-SHOCK registry.
AB  - INTRODUCTION: Mild therapeutic hypothermia (TH) is standard of care after cardiac
      arrest of any cause. However, its impact on on-treatment platelet reactivity and
      clinical outcome in patients with acute myocardial infarction (AMI) complicated
      by cardiogenic shock and undergoing PCI with P2Y12 receptor inhibitor treatment
      is less clear. METHODS AND RESULTS: For the ISAR-SHOCK registry, 145 patients
      with AMI, cardiogenic shock and primary PCI in two centers (Deutsches Herzzentrum
      Munchen and Klinikum rechts der Isar, Technical University Munich) between
      January 2009-May 2012 were analysed. Of these, 64 (44%) patients received TH
      treatment. The median [IQR] ADP-induced platelet aggregation following
      thienopyridine loading dose administration (clopidogrel in 95 and prasugrel in 50
      patients) did not differ between the two groups (419 [283-684] for TH vs. 355
      [207-710] AU x min for non-TH patients, P=0.22). After 30days follow-up, no
      significant differences were observed between both groups for mortality (42 vs.
      44 %, HR: 0.93, 95% CI [0.56-1.53], p=0.77), MI (6 vs. 6%, HR: 0.99 95% CI [0.27
      3.7], p=0.99) and TIMI minor bleedings (17 vs. 17%, HR 0.99 95% CI [0.45-2.18],
      p=0.98). TIMI major bleedings were numerically higher in the TH vs. non-TH cohort
      (25 % vs. 12 %, HR: 2.1 95% CI [0.95-4.63], p=0.07). Three definite stent
      thrombosis (ST) were observed in this registry and all STs occurred in the TH
      group of patients (p=0.09). CONCLUSION: Results of this registry suggest that TH
      does not negatively impact on platelet reactivity in shock patients receiving
      either clopidogrel or prasugrel. The numerically higher rate of major bleedings
      and the clustering of STs in the TH cohort warrant further investigation.

PMID- 25976449
TI  - Association between single nucleotide polymorphisms in thrombospondins genes and
      coronary artery disease: A meta-analysis.
AB  - OBJECTIVE: This study aimed to assess the association between single nucleotide
      polymorphisms in thrombospondin-1 (THBS1), thrombospondin-2 (THBS2),
      thrombospondin-4 (THBS4) and coronary artery disease (CAD) risk. METHODS:
      Electronic databases were searched before June, 2014 to obtain articles
      associated with thrombospondin polymorphisms and CAD risk. After identifying case
      control studies, odds ratios (ORs) and 95% confidence intervals (95% CIs) were
      used to pool effect sizes. Different effect models were used according to
      heterogeneity. Meta-regression and sensitivity analyses were performed to examine
      the heterogeneity source. Begg's funnel plot and Egger's test were conducted for
      publication bias. RESULTS: 13 studies involving 10,801 cases and 9,381 controls
      were included. Associations were observed between the THBS1 N700S polymorphism
      and CAD risk in general population(heterozygote model: OR=1.14, 95% CI: 1.03
      1.26; dominant model: OR=1.13, 95% CI: 1.00-1.29), European population
      (heterozygote model: OR=1.13, 95% CI: 1.00-1.27) and Asian population
      (heterozygote model: OR=1.57, 95% CI: 1.01-2.44; dominant model: OR=1.56, 95% CI:
      1.00-2.43). The THBS2 3' untranslated region (UTR) polymorphism and THBS4 A387P
      polymorphism were not associated with overall CAD risk. However, an association
      was observed between the THBS4 A387P polymorphism and CAD risk in the American
      population (allele model: OR=1.09, 95% CI: 1.00-1.18; homozygote model: OR=1.29,
      95% CI: 1.04-1.61; recessive model: OR=1.27, 95% CI: 1.02-1.58). CONCLUSIONS: The
      THBS1 N700S polymorphism was associated with increased CAD risk, especially in
      Asian and European populations. No association was observed between the THBS2 3'
      UTR polymorphism and CAD risk. The THBS4 A387P polymorphism was associated with
      increased CAD risk in the American population.

PMID- 25976450
TI  - Platelet microparticle generation assay for heparin-induced thrombocytopenia
      diagnosis: How should we express the results?

PMID- 25976451
TI  - Molecular epidemiology of Acinetobacter baumannii in different hospitals in
      Tripoli, Lebanon using bla(OXA-51-like) sequence based typing.
AB  - BACKGROUND: A. baumannii has emerged as an important nosocomial pathogen with an
      outstanding ability to acquire multidrug resistant mechanisms. In this study, we
      investigate the molecular epidemiology and carbapenem resistance mechanisms of A.
      baumannii in Tripoli, Northern Lebanon. METHODS: One hundred sixteen non
      duplicate isolates isolated between 2011 and 2013 in different hospitals in
      Tripoli, Lebanon from Lebanese patients and wounded Syrian patients during Syrian
      war were studied. Antibiotic susceptibility testing was determined by agar disc
      diffusion and Etest. Carbapenemase-encoding genes were investigated by PCR. All
      isolates were typed by bla OXA-51-like sequence based typing (SBT) and 57
      isolates were also analysed by MLST using Pasteur's scheme followed by eBURST
      analysis. RESULTS: Of the 116 isolates, 70 (60 %) showed a carbapenem resistance
      phenotype. The bla OXA-23 with an upstream insertion of ISAba1 was the major
      carbapenem resistance mechanism and detected in 65 isolates. Five isolates,
      including four from wounded Syrian patients and one from a Lebanese patient, were
      positive for bla NDM-1. bla OXA-51-like SBT revealed the presence of 14 variants,
      where bla OXA-66 was the most common and present in 73 isolates, followed by bla
      OXA-69 in 20 isolates. MLST analysis identified 17 sequence types (ST) and showed
      a concordance with bla OXA-51-like SBT. Each clonal complex (CC) had a specific
      bla OXA-51-like sequence such as CC2, which harboured bla OXA-66 variant, and CC1
      harbouring bla OXA-69 variant. NDM-1 producing isolates belonged to ST85 (4
      Syrian isolates) and ST25 (1 Lebanese isolate). CONCLUSIONS: Our results showed a
      successful predominance of international clone 2 with a widespread occurrence of
      OXA-23 carbapenemase in Lebanese hospitals. These findings emphasise the urgent
      need of effective measures to control the spread of A. baumannii in this country.

PMID- 25976453
TI  - A fast and direct spectrophotometric method for the simultaneous determination of
      methyl paraben and hydroquinone in cosmetic products using successive projections
      algorithm.
AB  - OBJECTIVE: To develop a simple and efficient spectrophotometric technique
      combined with chemometrics for the simultaneous determination of methyl paraben
      (MP) and hydroquinone (HQ) in cosmetic products, and specifically, to: (i)
      evaluate the potential use of successive projections algorithm (SPA) to
      derivative spectrophotometric data in order to provide sufficient accuracy and
      model robustness and (ii) determine MP and HQ concentration in cosmetics without
      tedious pre-treatments such as derivatization or extraction techniques which are
      time-consuming and require hazardous solvents. METHODS: The absorption spectra
      were measured in the wavelength range of 200-350 nm. Prior to performing
      chemometric models, the original and first-derivative absorption spectra of
      binary mixtures were used as calibration matrices. Variable selected by
      successive projections algorithm was used to obtain multiple linear regression
      (MLR) models based on a small subset of wavelengths. The number of wavelengths
      and the starting vector were optimized, and the comparison of the root mean
      square error of calibration (RMSEC) and cross-validation (RMSECV) was applied to
      select effective wavelengths with the least collinearity and redundancy.
      Principal component regression (PCR) and partial least squares (PLS) were also
      developed for comparison. The concentrations of the calibration matrix ranged
      from 0.1 to 20 MUg mL(-1) for MP, and from 0.1 to 25 MUg mL(-1) for HQ. The
      constructed models were tested on an external validation data set and finally
      cosmetic samples. RESULTS: The results indicated that successive projections
      algorithm-multiple linear regression (SPA-MLR), applied on the first-derivative
      spectra, achieved the optimal performance for two compounds when compared with
      the full-spectrum PCR and PLS. The root mean square error of prediction (RMSEP)
      was 0.083, 0.314 for MP and HQ, respectively. To verify the accuracy of the
      proposed method, a recovery study on real cosmetic samples was carried out with
      satisfactory results (84-112%). CONCLUSION: The proposed method, which is an
      environmentally friendly approach, using minimum amount of solvent, is a simple,
      fast and low-cost analysis method that can provide high accuracy and robust
      models. The suggested method does not need any complex extraction procedure which
      is time-consuming and requires hazardous solvents.

PMID- 25976452
TI  - Factors associated with relational coordination between health professionals
      involved in insulin initiation in the general practice setting for people with
      type 2 diabetes.
AB  - AIM: To examine associations between characteristics of general practice settings
      and primary healthcare providers (general practitioners and practice nurses) and
      the degree of relational coordination for the task of insulin initiation for type
      2 diabetes between primary healthcare providers and diabetes specialists.
      BACKGROUND: Relational coordination is a component of effective chronic disease
      management and can be used to measure collaboration and communication between
      health professionals. High levels of relational coordination may be important to
      support insulin initiation in general practice. DESIGN: Cross-sectional study.
      METHODS: Surveys were completed by general practitioners and practice nurses
      participating in the Stepping Up trial. Data on demographics, practice
      characteristics and relational coordination were collected between October 2012
      June 2014. Univariate and multivariate analyses examined factors associated with
      relational coordination. RESULTS: General practitioners (n = 174) and 115
      practice nurses from 78 general practices were included in the analysis. General
      practice characteristics associated with relational coordination were
      geographical location and number of administrative staff. Female general
      practitioners and older practice nurses reported lower relational coordination.
      Practice nurses with diabetes educator qualifications and experience in insulin
      initiation reported higher relational coordination. CONCLUSION: An expanded role
      and experience of practice nurses in diabetes care increased relational
      coordination and has the potential to deliver more effective chronic disease
      management in general practice. Practice and health professional characteristics
      should be taken into account when designing models of care to increase insulin
      initiation.

PMID- 25976454
TI  - Flutamide alters beta-catenin expression and distribution, and its interactions
      with E-cadherin in the porcine corpus luteum of mid- and late pregnancy.
AB  - This study examined whether flutamide-induced androgen deficiency during mid- and
      late pregnancy in pigs affected luteal expression of adherens junction protein,
      beta-catenin, and its interactions with E-cadherin. Flutamide (50 mg/kg body
      weight) was administered into pregnant gilts between days 43-49 (GD50F), 83-89
      (GD90F) or 101-107 (GD108F) of gestation. Corpora lutea (CLs) were obtained on
      day 50, 90 or 108 of pregnancy (n=8-11 per each group). Total beta-catenin and E
      cadherin expression was examined at mRNA (real-time PCR) and protein (Western
      blot) level. Moreover, subcellular beta-catenin fractions were extracted and
      immunoblotted. Immunohistochemistry was used for beta-catenin localization. To
      determine whether flutamide disturbs beta-catenin/E-cadherin mutual interactions,
      coimmunoprecipitation using anti-beta-catenin antibody was performed.
      Furthermore, phosphorylation of E-cadherin was assessed. Flutamide exposure led
      to decreased beta-catenin mRNA expression in all examined groups (p<0.001 or
      p<0.01), but protein level was lower only in the GD90F and GD108F groups
      (p<0.05). E-cadherin mRNA (p<0.05 or p<0.01) and protein (p<0.05) levels were up
      regulated in all flutamide-treated groups when compared to controls. beta-catenin
      was predominantly found in membranes of luteal cells with no significant changes
      after antiandrogen treatment. beta-catenin/E-cadherin complexes were more
      abundant in the GD90F (p<0.05) and GD108F (p<0.01) groups than in controls due to
      enhanced E-cadherin phosphorylation at serine 838/840 in those animals (p<0.05).
      Overall, although androgen deficiency affected beta-catenin expression in the CL
      of pregnancy in pigs, a compensatory mechanism by enhanced interactions with E
      cadherin is possible. Thus, androgen signaling via androgen receptors appears to
      be crucial in the regulation of luteal cells cross-talk. 

PMID- 25976455
TI  - Children's rugby: outdated view that risk of injury is character building.

PMID- 25976456
TI  - [Fitness to drive in North America].

PMID- 25976457
TI  - Tintin's travel traumas: Health issues affecting the intrepid globetrotter.
AB  - BACKGROUND: Despite the highly hazardous life-style led by comic book characters
      such as Tintin, we are unaware of any previous systematic description of the
      challenges and health impairments faced by Tintin in the course of his
      adventures. METHODS: We evaluated the spectrum of health impairments (HIs) that
      Tintin sustained in his 23 adventures as well as their causes, consequences, and
      relation to travel. We diagnosed Tintin's HIs according to descriptive terms in
      the text. We then classified HIs as traumatic and non-traumatic, and
      distinguished between intentional (those perpetrated by others) and unintentional
      events. RESULTS: We found 236 events leading to 244 HIs, 13 kidnappings, six
      hospitalisations and two surgical procedures. There was a median of 8
      HIs/adventure (range 1-30/adventure). The mean number of HIs per adventure was
      much greater before 1945 than subsequently (14.9 vs. 6.1; P=0.002), which was
      also true of the number of kidnappings (11 vs. 2; P=0.001). Of the 244 HIs, there
      were 191 cases of trauma (78.3%) and 53 non-traumatic problems (21.7%). The most
      common form of trauma was concussion (62%) whereas the most common forms of non
      traumatic problems were sleep problems (15.1%), depression/anxiety (13%), and gas
      or chloroform poisoning (13%). Overall, we found 46 losses of consciousness
      (LoC), including 29 traumatic and 17 non-traumatic LoCs. Of the 236 events, there
      were 69 (29%) perpetrated by others against Tintin (including 55 homicide
      attempts), and 167 (71%) events that were not (including 69 events related to
      Tintin's actions). CONCLUSION: Tintin's almost superhuman qualities, a luxury
      afforded him by his fictional status, make him highly resistant to trauma. He is
      also not susceptible to the usual travel-related illnesses but is easily
      influenced by his friends and Snowy, his faithful hound.

PMID- 25976458
TI  - Distinguishing clonal evolution from so-called secondary acute myelogenous
      leukemia: Adhering to unifying concepts of the genetic basis of leukemogenesis.

PMID- 25976459
TI  - Effect of systemic heparan sulfate haploinsufficiency on steady state
      hematopoiesis and engraftment of hematopoietic stem cells.
AB  - Heparan sulfate (HS) proteoglycans on stromal and hematopoietic stem/progenitor
      cells (HSPC) help form the stem cell niche, co-localize molecules that direct
      stem cell fate, and modulate HSPC homing and retention. Inhibition of HS function
      mobilizes marrow HSPC. In vitro, HSPC maintenance is influenced by stromal HS
      structure and concentration. Because inhibition of HS activity or synthesis may
      be developed for HSPC transplantation, it is important to examine if systemic HS
      deficiency influences hematopoiesis in vivo. In a transgenic mouse model of HS
      haploinsufficiency, we examined endogenous hematopoiesis and engraftment of
      allogeneic bone marrow. Endogenous hematopoiesis was normal except gender
      specific alterations in peripheral blood monocyte and platelet counts. Donor
      engraftment was achieved in all mice following myeloablative irradiation, but HS
      deficiency in the stromal microenvironment, on HSPC, or both (the 3 test
      conditions), was associated with a trend towards lower donor engraftment
      percentage in the bone marrow. Following non-myeloablative irradiation,
      competitive engraftment was achieved in 22% of mice in the test conditions, vs
      50% of control animals (P = 0.03). HS deficiency did not re-direct donor
      engraftment from bone marrow to spleen or liver. Normal HS levels in the stromal
      microenvironment and HSPC are required for HSPC engraftment following non
      myeloablative conditioning.

PMID- 25976460
TI  - Genotype-phenotype correlation and report of novel mutations in beta-globin gene
      in thalassemia patients.
AB  - Heterogeneity in thalassemia is due to various modifying factors viz.
      coinheritance of alpha-gene defects, abnormal hemoglobin, XmnI polymorphism,
      variation in repeat sequences present in LCR, and silencer region of the gene.
      The present work on populations from eastern regions of India was undertaken to
      study the genetic profile of heterogeneity in thalassemia patients. Mutation
      analysis in 126 index families revealed the presence of 3 novel mutations: CD2 (
      A) in the 1st exon, -42 (C-G), and -223 (T-C) in the promoter region of beta
      globin gene. The modifying effect of coexisting alpha-gene defects, and abnormal
      Hb (HbS) was clearly observed in our study, however ameliorating effect of T
      allele of XmnI polymorphism was not found. Analysis of the regulatory regions
      (LCR) exhibited new combinations (CA(15)TA(5) and CA(13)TA(8)) in HS1 region and
      one (AT)(10)T(3) in (AT)(x)T(y )silencer region. Thus disparate factors, when
      considered together, were able to explain several of the thalassemic phenotypes,
      otherwise not explained by the beta globin mutations. However, there were still
      some cases in this group whose molecular origin could not be ascertained. Our
      findings confirm not only the extensive genotypic and clinical heterogeneity in
      beta thalassemia but also the need to look for more modulators and modifiers to
      better understand the genotype-phenotype correlation in thalassemia.

PMID- 25976461
TI  - Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone
      marrow and spleen.
AB  - Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid
      stimulating hormone, and prolactin. The phenotype of these mice demonstrates
      irregularities in the immune system with skewing of the normal cytokine milieu
      towards a more anti-inflammatory environment. However, the hematopoietic stem and
      progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice
      has not been well characterized. We found that there was a significant decrease
      in overall cell count when comparing the BM and spleen of 4-5 month old dwarf
      mice to their littermate controls. Upon adjusting counts to differences in body
      weight between the dwarf and control mice, the number of granulocyte-macrophage
      progenitors, confirmed by immunophenotyping and colony-formation assay was
      increased in the BM. In contrast, the numbers of all myeloid progenitor
      populations in the spleen were greatly reduced, as confirmed by colony-formation
      assays. This suggests that there is a shift of myelopoiesis from the spleen to
      the BM of Ames dwarf mice; however, this shift does not appear to involve
      erythropoiesis. The reasons for this unusual shift in spleen to marrow
      hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the
      decreased hormone levels in these mice.

PMID- 25976462
TI  - Mechanism of interleukin-13 production by granulocyte-macrophage colony
      stimulating factor-dependent macrophages via protease-activated receptor-2.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes
      classically activated M1 macrophages. GM-CSF upregulates protease-activated
      receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil
      elastase (HNE) regulates cytokine production. AIM: This study investigated the
      mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent
      macrophages stimulated with HNE. METHODS: Adherent macrophages were obtained from
      primary cultures of human mononuclear cells. After stimulation with HNE to
      activate the mitogen-activated protein kinase/extracellular signal-regulated
      kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed
      by the reverse transcriptase-polymerase chain reaction and enzyme-linked
      immunosorbent assay, respectively. RESULTS: PAR-2 protein was detected in GM-CSF
      dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1
      inhibitor) increased IL-13 production, even at higher concentrations.
      Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a
      concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor)
      nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB
      8 (a calcium chelator) diminished IL-13 production. DISCUSSION: Stimulation with
      HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1
      macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2
      signaling pathway.

PMID- 25976463
TI  - Co-inheritance of novel ATRX gene mutation and globin (alpha & beta) gene
      mutations in transfusion dependent beta-thalassemia patients.
AB  - alpha-Thalassemia X-linked mental retardation syndrome is a rare inherited
      intellectual disability disorder due to mutations in the ATRX gene. In our
      previous study of the prevalence of beta-thalassemia mutations in the Eastern
      Province of Saudi Arabia, we confirmed the widespread coinheritance of alpha
      thalassemia mutation. Some of these subjects have a family history of mental
      retardation, the cause of which is unknown. Therefore, we investigated the
      presence or absence of mutations in the ATRX gene in these patients. Three exons
      of the ATRX gene and their flanking regions were directly sequenced. Only four
      female transfusion dependent beta-thalassemia patients were found to be carriers
      of a novel mutation in the ATRX gene. Two of the ATRX gene mutations, c.623delA
      and c.848T>C were present in patients homozygous for IVS I-5(G->C) and homozygous
      for Cd39(C -> T) beta-thalassemia mutation, respectively. While the other two
      that were located in the intronic region (flanking regions), were present in
      patients homozygous for Cd39(C -> T) beta-thalassemia mutation. The two subjects
      with the mutations in the coding region had family members with mental
      retardation, which suggests that the novel frame shift mutation and the missense
      mutation at coding region of ATRX gene are involved in ATRX syndrome.

PMID- 25976464
TI  - Plasmodium vivax: N-terminal diversity in the blood stage SERA genes from Indian
      isolates.
AB  - Worldwide malaria risk due to Plasmodium vivax makes development of vaccine
      against P. vivax, a high priority. Serine Repeat Antigen of P. vivax (PvSERA) is
      a multigene family of blood stage proteins with 12 homologues. Sequence diversity
      studies are important for understanding them as potential vaccine candidates. No
      information on N-terminal diversity of these genes is available in literature. In
      this paper, we evaluate the genetic polymorphism of N-terminal regions of the
      highly expressed member PvSERA4 and PvSERA5 genes from Indian field isolates. Our
      results show that PvSERA4 has deletions and insertions in Glutamine rich
      tetrameric repeat units contributing to its diversity. PvSERA5 also exhibits high
      genetic diversity with non-synonymous substitutions leading to identification of
      novel haplotypes from India. Our first report helps in elucidating the allelic
      variants of PvSERA genes in this region and contributes to evaluating their
      efficacy as vaccine candidates. 

PMID- 25976465
TI  - No increase of JAK2 46/1 haplotype frequency in essential thrombocythemia with
      CALR mutations: Functional effect of the haplotype limited to allele with
      JAK2V617F mutation but not CALR mutation.
AB  - The true frequency of the JAK2 46/1 haplotype in patients of myeloproliferative
      neoplasms (MPN) with CALR mutations was unknown. Totally 187 MPN cases with
      diagnosis of polycythemia vera (PV) and essential thrombocythemia (ET) were
      recruited. The frequency of 46/1 haplotype was significantly higher in JAK2V617F
      positive PV (51%, p < 0.001) and ET (41%, p = 0.005) compared to normal controls.
      The exact location of JAK2V617F mutation was located at the cis-46/1 haplotype in
      86.4% (32/37) PV patients and 87.5% (28/32) ET patients, respectively. Among the
      51 patients of ET without JAK2V617F mutation, 38 (75%) patients harbored CALR
      mutations and 3 patients had MPL mutation. The frequency of 46/1 haplotype in the
      38 ET patients with CALR mutations was 27%, which is not significantly different
      from that of normal control (p value = 0.879). Compared to non-46/1 haplotype,
      the presence of 46/1 haplotype had a trend to have higher white blood cell count
      in JAK2V617F-mutated PV and ET patients but not in CALR-mutated ET. We conclude
      that the 46/1 haplotype could have functioning effect but only in the context of
      JAK2V617F mutation.

PMID- 25976468
TI  - The effects of hydroxyurea and bone marrow transplant on Anti-Mullerian hormone
      (AMH) levels in females with sickle cell anemia.
AB  - Gonadal hypofunction is described in male and female patients with sickle cell
      anemia (SCA) after bone marrow transplant (BMT) and in males treated with
      hydroxyurea (HU). Anti-Mullerian hormone (AMH) is a serum marker of ovarian
      reserve. This study describes AMH and follicle-stimulating hormone (FSH) levels
      in female SCA subjects treated with supportive care (SCA-SC), HU (SCA-HU) and BMT
      (SCA-BMT). SCA (SS/Sbeta(0)) subjects not on HU, on HU and status-post BMT, ages
      10-21 years were recruited. SCA-HU subjects were treated with HU >= 20 mg/kg for
      >= 12 consecutive months. SCA-BMT subjects had received busulfan and
      cyclophosphamide. Serum AMH and random FSH levels were obtained. Diminished
      ovarian reserve (DOR) was defined as AMH level <5th percentile for age-matched
      controls. Subjects also with FSH >40 IU/L were classified as having premature
      ovarian insufficiency (POI). 14 SCA-SC (14.5 +/- 2.7 years), 33 SCA-HU (14.4 +/-
      2.4 years) and 9 SCA-BMT (14.3 +/- 2.7 years) females were included. AMH was
      undetectable in all SCA-BMT subjects and <5th percentile in 24% of SCA-HU
      subjects. FSH was menopausal (>40 IU/L) in 88.9% of SCA-BMT subjects. All SCA-BMT
      subjects and 24% of subjects on HU had DOR; 89% of SCA-BMT subjects had POI. AMH
      and FSH may be useful tools in assessing ovarian reserve and function.

PMID- 25976466
TI  - Diagnosis and management of acquired aplastic anemia in childhood. Guidelines
      from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian
      Association (AIEOP).
AB  - Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by
      pancytopenia and hypoplastic bone marrow. The incidence is 2-3/million
      inhabitants/year, in Europe, but higher in East Asia. Survival in severe aplastic
      anemia (SAA) has markedly improved in the past 2 decades because of advances in
      hematopoietic stem cell transplantation, immunosuppressive and biologic drugs,
      and supportive care. In SAA hematopoietic stem cell transplant (HSCT) from a
      matched sibling donor (MSD) is the treatment of choice. If a MSD is not
      available, the options include immunosuppressive therapy (IST) or unrelated donor
      HSCT. The objective of this guideline is to provide healthcare professionals with
      clear guidance on the diagnosis and management of pediatric patients with AA. A
      preliminary, evidence-based document issued by a group of pediatric hematologists
      was discussed, modified and approved during a series of "Consensus Conferences"
      according to procedures previously validated by the AIEOP Board. The guidelines
      highlight the importance of referring pediatric patients with AA to pediatric
      centers with long experience in diagnosis, differential diagnosis, management,
      supportive care and follow-up of AA.

PMID- 25976467
TI  - Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-kappaB) gene
      and blood cell adhesion molecule expression in patients with homozygous sickle
      cell disease.
AB  - Chronic inflammation and reduced blood levels of omega-3 fatty acids (n-3) are
      known characteristics of sickle cell disease (SCD).The anti-inflammatory
      properties of n-3 fatty acids are well recognized. Omega-3 treated (n = 24),
      hydroxyurea (HU) treated (n = 18), and n-3 untreated (n=21) homozygous SCD
      patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5-16
      years), gender and socioeconomic status were studied. According to age (5-10) or
      (11-16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA)
      and 39.0mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned
      to n-3 treated and n-3 untreated groups, respectively. Hydroxyurea treated group
      was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic
      and blood cell markers of inflammation was investigated. The n-3 treated group
      had higher levels of DHA and EPA (p < 0.001) and lower white blood cell count and
      monocyte integrin (p < 0.05) compared with the n-3 untreated. No difference was
      detected between the two groups regarding C-reactive protein, granulocytes
      integrin and selectin, plasma tumour necrosis factor-alpha and interleukin-10.
      The n-3 treated group had lowered nuclear factor-kappa B (NF-kappaB) gene
      expression compared to n-3 untreated and HU treated groups (p < 0.05). This study
      provides evidence that supplementation with n-3 fatty acids may ameliorate
      inflammation and blood cell adhesion in patients with SCD.

PMID- 25976469
TI  - Development of a capillary zone electrophoresis method for rapid determination of
      human globin chains in alpha and beta-thalassemia subjects.
AB  - Thalassemia is an inherited autosomal recessive blood disorder characterized by
      the underproduction of globin chains as a consequence of globin gene defects,
      resulting in malfunctioning red blood cells and oxygen transport. Analysis of
      globin chains is an important aspect of thalassemia research. In this study we
      developed a capillary zone electrophoresis (CZE) method for human globin
      determination in the diagnosis of thalassemia and hemoglobin variants. To
      demonstrate the utility of this approach, alpha/beta area ratios were determined
      for samples from 310 thalassemia patients and healthy controls. The separation
      was performed on uncoated capillary with simple preparation. Distinct globin
      peaks were resolved in 17 min, and coefficients of variation (CV) for migration
      time and areas ranged from 0.37%-1.69% and 0.46%-6.71%, respectively. Receiver
      operating characteristic (ROC) curve analysis of the alpha/beta area ratios gave
      100% sensitivity and specificity for indicating beta-TI/TM, and 100% sensitivity
      and 97.4% specificity for Hb H disease. Hemoglobin G-Honolulu (Hb G-Honolulu) and
      Hb Westmead (Hb WS) were successfully detected using this CZE method. This
      automated methodology is simple, rapid and cost-effective for the fast
      determination of human globin chains, which could be an important diagnostic tool
      in the field of hemoglobinopathies.

PMID- 25976470
TI  - The long-term effects of radioactive phosphorous synoviorthesis on hemophilic
      arthropathy.
AB  - BACKGROUND: Radioactive synoviorthesis was carried out by an injection of
      radioactive materials into the joint that has been known as a successful
      alternative treatment to invasive surgical synovectomy. This study was designed
      to evaluate short-term and long-term results and complications of radioactive
      synovectomy of hemophilic arthropathy using radioactive phosphorus. MATERIALS AND
      METHODS: This study was conducted on 40 patients with hemophilic arthropathy.
      After obtaining clotting factors, the intra-articular injections of radioactive
      phosphorus were done. Thirteen patients were evaluated during 36 months (short
      term follow-up) and 27 patients were followed up for more than 36 months (long
      term follow-up). Patients were evaluated for hemarthrosis, factor consumption per
      month, joint range of motion (ROM) and clinical and radiological involvement
      grade. RESULTS: The patients mean age was 22.9 +/- 6.6 and there were 38 men and
      2 women. Consumption of clotting factors was significantly reduced in the short
      term follow-up of patients (p < 0.05), but there was no significant difference in
      the long-term follow-up (p > 0.05). ROM decreased significantly in the long-term
      follow-up (p < 0.05). Radiologic evaluation showed significantly increased
      involvement in their joints (p < 0.05). CONCLUSION: Using radioactive
      synoviorthesis led in decreased consumption of clotting factors and the
      hemarthrosis incidence in short term but it did not have significant impact on
      clinical situation (ROM) and radiological findings of hemophilic patients in long
      term follow-up.

PMID- 25976472
TI  - Genetics factors associated with myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are a clinically and cytogenetically
      heterogeneous group of clonal diseases. Clonal chromosomal abnormalities are
      observed in 30-50% of patients with MDS. The deletions are among the most common
      alterations, and often involve the long arms of chromosomes 5, 7, 8, 13, and 20
      and the short arms of chromosomes 12 and 17. The advent of new technologies for
      the detection of genetic abnormalities led to the description of a new set of
      recurrent mutations, leading to new insights into the pathophysiology of MDS. The
      recent recognition that genes involved in the regulation of histone function
      (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are
      frequently mutated in MDS, has led to the proposal that there is an important
      link between genetic and epigenetic alterations in this disease. In fact,
      regulatory factors have also been considered as miR-143/miR-145, miR-146a, miR
      125a and MiR-21. Somatic mutations may influence the clinical phenotype but are
      not included in current prognostic scoring systems. In recent years research has
      brought new insights into these diseases, but few of the findings are
      sufficiently robust to be incorporated into the clinical routine at this time.
      Thus, the aim of this study was to review the role of genetic factors involved in
      the diagnosis and development of the different phenotypes of MDS. 

PMID- 25976471
TI  - Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The
      controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes.
AB  - Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism.
      The most common form of the disease is Classic or type 1 HH, mainly caused by a
      biallelic missense p.Cys282Tyr (c.845G>A) mutation in the HFE gene. However, the
      penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both
      biochemical and clinical expressivity. Lack of penetrance is thought to be caused
      by several genetic and environmental factors. Recently, a lot of evidences on HH
      genetic modifiers were produced, often without conclusive results. We
      investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene,
      rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and
      rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate
      their role in an independent cohort of 109 HH type 1 patients. Our results make
      it likely the role of rs10421768, rs235756, rs2230267 and rs1439816
      polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH
      expressivity. In addition, previous and our findings support a hypothetical
      multifactorial model of HH, characterized by a principal gene (HFE in HH type 1)
      and minor genetic and environmental factors that still have to be fully
      elucidated.

PMID- 25976473
TI  - Thalassemia major between liver and heart: Where we are now.
AB  - The aim of the study was to assess the current state in terms of liver and heart
      iron overload as well as of liver and heart related morbidity and mortality in a
      large cohort of thalassemia patients. Myocardial iron loading was present in
      28.9% patients, which was severe in 3.2%. Liver iron was normal in 9.3% and
      severe in 15%. The rate of cardiac deaths started to decrease between 2000 and
      2003 and dropped significantly afterwards. The prescription of combination
      therapy soon after the hospital admission for decompensated heart failure was
      associated with a decrease in the short-term mortality. In 111 adult patients who
      underwent liver elastometry, 14 HCVRNA positive subjects and 2 HCVRNA negative,
      had stiffness values suggestive of cirrhosis. No cases of hepatocarcinoma were
      reported. Liver "iron free foci" occurred in a HCV negative patient and the
      occurrence of a malignant epithelioid hemangioendothelioma led to liver
      transplantation in another. The study suggests that a subset of patients
      continues to develop progressive hemosiderosis that may lead to cardiac disease
      and death. Beyond its key role in preventing myocardial iron overload, liver iron
      chelation is essential for hampering the onset of hepatic tumors, which may not
      be limited to hepatocarcinoma. 

PMID- 25976474
TI  - Mitochondrial uncoupling protein (UCP2) gene expression is regulated by miR-2909.
AB  - Reversible decoupling of glycolysis from aerobic-respiration has been widely
      recognized to be a crucial step in tailoring immune response by the human cells.
      In this context, the study reported here revealed for the first time that
      cooperativity between Apoptosis Antagonizing Transcription Factor (AATF) mRNA and
      miR-2909 within cellular AATF RNome ensures the regulation of mitochondrial
      uncoupling protein 2 (UCP2) expression in a cyclic fashion and this phenomenon is
      substantiated when the immune cells face high glucose threat. 

PMID- 25976476
TI  - Papillary-cystic pattern is characteristic in mammary analogue secretory
      carcinomas but is rarely observed in acinic cell carcinomas of the salivary
      gland.
AB  - Mammary analogue secretory carcinoma (MASC) has a specific ETV6-NTRK3
      translocation and morphologically overlaps with acinic cell carcinoma (AciCC).
      Before the recognition of MASC, in AciCC, four histologic patterns were
      identified including microcystic, solid, papillary-cystic, and follicular. The
      aim of this study was to evaluate histologic patterns in these two neoplasms
      through comprehensive histologic subtyping. Using fluorescence in situ
      hybridization (FISH), we identified 14 cases of MASC and 21 cases of AciCC. We
      used comprehensive histologic subtyping to provide a semiquantitive assessment of
      histologic patterns in each tumor and performed immunohistochemical analyses
      including S100/vimentin/mammaglobin/DOG1. MASC often presented papillary-cystic
      patterns without a solid component, previously considered to be one of the four
      major patterns associated with AciCC. However, in our study, this histologic
      feature was rarely seen in AciCC and more characteristic of MASC. In aspiration
      cytology samples, MASC was associated with more cellular atypia. An
      immunohistochemical panel of S100/mammaglobin/DOG1 was found useful for
      differential diagnosis. Comprehensive subtyping of histologic patterns is a
      useful screening method prior to initiation of molecular testing.

PMID- 25976477
TI  - Cardiovascular adaptation in athletes.
AB  - Millions of athletes train for and participate in competitive athletics each
      year. Many of these athletes will present to a cardiovascular specialist with
      signs or symptoms that might indicate heart disease and these athletes/patients
      will ask for advice on their ability to continue to train and compete safely. By
      virtue of their training, athletes' hearts may undergo significant structural and
      electrical change, presenting a special challenge for the cardiovascular
      specialist. It is important to understand normal adaptive changes in order to
      separate normal physiology from pathology. 

PMID- 25976475
TI  - Visualizing translocation dynamics and nascent transcript errors in paused RNA
      polymerases in vivo.
AB  - BACKGROUND: Transcription elongation is frequently interrupted by pausing signals
      in DNA, with downstream effects on gene expression. Transcription errors also
      induce prolonged pausing, which can lead to a destabilized genome by interfering
      with DNA replication. Mechanisms of pausing associated with translocation blocks
      and misincorporation have been characterized in vitro, but not in vivo. RESULTS:
      We investigate the pausing pattern of RNA polymerase (RNAP) in Escherichia coli
      by a novel approach, combining native elongating transcript sequencing (NET-seq)
      with RNase footprinting of the transcripts (RNET-seq). We reveal that the G-dC
      base pair at the 5' end of the RNA-DNA hybrid interferes with RNAP translocation.
      The distance between the 5' G-dC base pair and the 3' end of RNA fluctuates over
      a three-nucleotide width. Thus, the G-dC base pair can induce pausing in post
      translocated, pre-translocated, and backtracked states of RNAP. Additionally, a
      CpG sequence of the template DNA strand spanning the active site of RNAP inhibits
      elongation and induces G-to-A errors, which leads to backtracking of RNAP. Gre
      factors efficiently proofread the errors and rescue the backtracked complexes. We
      also find that pausing events are enriched in the 5' untranslated region and
      antisense transcription of mRNA genes and are reduced in rRNA genes. CONCLUSIONS:
      In E. coli, robust transcriptional pausing involves RNAP interaction with G-dC at
      the upstream end of the RNA-DNA hybrid, which interferes with translocation. CpG
      DNA sequences induce transcriptional pausing and G-to-A errors.

PMID- 25976478
TI  - The shutdown dissociation scale (shut-d).
AB  - The evolutionary model of the defense cascade by Schauer and Elbert (2010)
      provides a theoretical frame for a short interview to assess problems underlying
      and leading to the dissociative subtype of posttraumatic stress disorder. Based
      on known characteristics of the defense stages "fright," "flag," and "faint," we
      designed a structured interview to assess the vulnerability for the respective
      types of dissociation. Most of the scales that assess dissociative phenomena are
      designed as self-report questionnaires. Their items are usually selected based on
      more heuristic considerations rather than a theoretical model and thus include
      anything from minor dissociative experiences to major pathological dissociation.
      The shutdown dissociation scale (Shut-D) was applied in several studies in
      patients with a history of multiple traumatic events and different disorders that
      have been shown previously to be prone to symptoms of dissociation. The goal of
      the present investigation was to obtain psychometric characteristics of the Shut
      D (including factor structure, internal consistency, retest reliability,
      predictive, convergent and criterion-related concurrent validity). A total
      population of 225 patients and 68 healthy controls were accessed. Shut-D appears
      to have sufficient internal reliability, excellent retest reliability, high
      convergent validity, and satisfactory predictive validity, while the summed score
      of the scale reliably separates patients with exposure to trauma (in different
      diagnostic groups) from healthy controls. The Shut-D is a brief structured
      interview for assessing the vulnerability to dissociate as a consequence of
      exposure to traumatic stressors. The scale demonstrates high-quality psychometric
      properties and may be useful for researchers and clinicians in assessing shutdown
      dissociation as well as in predicting the risk of dissociative responding. 

PMID- 25976479
TI  - Altered mechanical state in the embryonic heart results in time-dependent
      decreases in cardiac function.
AB  - Proper blood flow patterns are critical for normal cardiac morphogenesis, a
      process that occurs rapidly in order to support further development of all tissue
      and organs. Previously, intracardiac fluid forces have been shown to play a
      critical role in cardiac morphogenesis. Altered blood flow in early development
      can result in an array of cardiac defects including ventricular septal defects,
      valve malformations, and impaired cardiac looping. However, given the dynamic and
      highly transient nature of cardiac morphogenesis, time dependency of the
      mechanical environment as an epigenetic factor in relation to intracardiac forces
      must be significant. Here, we show that abnormal cardiac loading adversely
      influences cardiac morphology only during certain time windows, thus confirming
      that mechanical factors are a time-dependent epigenetic factor. To illustrate
      this, groups of zebrafish embryos were spaced at 6-h increments from 24 to 48 h
      post-fertilization (hpf) in which embryos were centrifuged to generate a
      noninvasive alteration of cardiac preload in addition to an overall hypergravity
      environment. We found that earlier and later treatment groups responded with
      altered morphology and function, while the group with altered preload from 30 to
      36 hpf had no effect. These results demonstrate the inherently time-dependent
      nature of epigenetic factors as pertaining to intracardiac forces and external
      mechanical factors. Further, it underscores the highly coupled nature of
      programmed biology and mechanical forces during cardiac morphogenesis. Future
      studies with respect to surgical correction during cardiac morphogenesis must
      consider timing to optimize therapeutic impact. 

PMID- 25976480
TI  - Air quality and climate connections.

PMID- 25976481
TI  - Air quality and climate connections.
AB  - Multiple linkages connect air quality and climate change. Many air pollutant
      sources also emit carbon dioxide (CO2), the dominant anthropogenic greenhouse gas
      (GHG). The two main contributors to non-attainment of U.S. ambient air quality
      standards, ozone (O3) and particulate matter (PM), interact with radiation,
      forcing climate change. PM warms by absorbing sunlight (e.g., black carbon) or
      cools by scattering sunlight (e.g., sulfates) and interacts with clouds; these
      radiative and microphysical interactions can induce changes in precipitation and
      regional circulation patterns. Climate change is expected to degrade air quality
      in many polluted regions by changing air pollution meteorology (ventilation and
      dilution), precipitation and other removal processes, and by triggering some
      amplifying responses in atmospheric chemistry and in anthropogenic and natural
      sources. Together, these processes shape distributions and extreme episodes of O3
      and PM. Global modeling indicates that as air pollution programs reduce SO2 to
      meet health and other air quality goals, near-term warming accelerates due to
      "unmasking" of warming induced by rising CO2. Air pollutant controls on CH4, a
      potent GHG and precursor to global O3 levels, and on sources with high black
      carbon (BC) to organic carbon (OC) ratios could offset near-term warming induced
      by SO2 emission reductions, while reducing global background O3 and regionally
      high levels of PM. Lowering peak warming requires decreasing atmospheric CO2,
      which for some source categories would also reduce co-emitted air pollutants or
      their precursors. Model projections for alternative climate and air quality
      scenarios indicate a wide range for U.S. surface O3 and fine PM, although
      regional projections may be confounded by interannual to decadal natural climate
      variability. Continued implementation of U.S. NOx emission controls guards
      against rising pollution levels triggered either by climate change or by global
      emission growth. Improved accuracy and trends in emission inventories are
      critical for accountability analyses of historical and projected air pollution
      and climate mitigation policies. IMPLICATIONS: The expansion of U.S. air
      pollution policy to protect climate provides an opportunity for joint mitigation,
      with CH4 a prime target. BC reductions in developing nations would lower the
      global health burden, and for BC-rich sources (e.g., diesel) may lessen warming.
      Controls on these emissions could offset near-term warming induced by health
      motivated reductions of sulfate (cooling). Wildfires, dust, and other natural PM
      and O3 sources may increase with climate warming, posing challenges to
      implementing and attaining air quality standards. Accountability analyses for
      recent and projected air pollution and climate control strategies should underpin
      estimated benefits and trade-offs of future policies.

PMID- 25976482
TI  - Evaluation and application of site-specific data to revise the first-order decay
      model for estimating landfill gas generation and emissions at Danish landfills.
AB  - Methane (CH4) generated from low-organic waste degradation at four Danish
      landfills was estimated by three first-order decay (FOD) landfill gas (LFG)
      generation models (LandGEM, IPCC, and Afvalzorg). Actual waste data from Danish
      landfills were applied to fit model (IPCC and Afvalzorg) required categories. In
      general, the single-phase model, LandGEM, significantly overestimated
      CH4generation, because it applied too high default values for key parameters to
      handle low-organic waste scenarios. The key parameters were biochemical
      CH4potential (BMP) and CH4generation rate constant (k-value). In comparison to
      the IPCC model, the Afvalzorg model was more suitable for estimating
      CH4generation at Danish landfills, because it defined more proper waste
      categories rather than traditional municipal solid waste (MSW) fractions.
      Moreover, the Afvalzorg model could better show the influence of not only the
      total disposed waste amount, but also various waste categories. By using
      laboratory-determined BMPs and k-values for shredder, sludge, mixed bulky waste,
      and street-cleaning waste, the Afvalzorg model was revised. The revised model
      estimated smaller cumulative CH4generation results at the four Danish landfills
      (from the start of disposal until 2020 and until 2100). Through a CH4mass balance
      approach, fugitive CH4emissions from whole sites and a specific cell for shredder
      waste were aggregated based on the revised Afvalzorg model outcomes. Aggregated
      results were in good agreement with field measurements, indicating that the
      revised Afvalzorg model could provide practical and accurate estimation for
      Danish LFG emissions. This study is valuable for both researchers and engineers
      aiming to predict, control, and mitigate fugitive CH4emissions from landfills
      receiving low-organic waste. IMPLICATIONS: Landfill operators use the first-order
      decay (FOD) models to estimate methane (CH4) generation. A single-phase model
      (LandGEM) and a traditional model (IPCC) could result in overestimation when
      handling a low-organic waste scenario. Site-specific data were important and
      capable of calibrating key parameter values in FOD models. The comparison study
      of the revised Afvalzorg model outcomes and field measurements at four Danish
      landfills provided a guideline for revising the Pollutants Release and Transfer
      Registers (PRTR) model, as well as indicating noteworthy waste fractions that
      could emit CH4at modern landfills.

PMID- 25976483
TI  - Vehicle emissions of radical precursors and related species observed in the 2009
      SHARP campaign.
AB  - The 2009 Study of Houston Atmospheric Radical Precursors (SHARP) field campaign
      had several components that yielded information on the primary vehicular
      emissions of formaldehyde (HCHO) and nitrous acid (HONO), in addition to many
      other species. Analysis of HONO measurements at the Moody Tower site in Houston,
      TX, yielded emission ratios of HONO to the vehicle exhaust tracer species NOx and
      CO of 14 pptv/ppbv and 2.3 pptv/ppbv, somewhat smaller than recently published
      results from the Galleria site, although evidence is presented that the Moody
      Tower values should be upper limits to the true ratios of directly emitted HONO,
      and are consistent with ratios used in current standard emissions models. Several
      other Moody Tower emission ratios are presented, in particular a value for
      HCHO/CO of 2.4 pptv/ppbv. Considering only estimates of random errors, this would
      be significantly lower than a previous value, though the small sample size and
      possible systematic differences should be taken into account. Emission factors
      for CO, NOx, and HCHO, as well as various volatile organic compounds (VOCs), were
      derived from mobile laboratory measurements both in the Washburn Tunnel and in on
      road exhaust plume observations. These two sets of results and others reported in
      the literature all agree well, and are substantially larger than the CO, NOx, and
      HCHO emission factors derived from the emission ratios reported from the Galleria
      site. IMPLICATIONS: Emission factors for the species measured in the various
      components of the 2009 SHARP campaign in Houston, TX, including HCHO, HONO, CO,
      CO2, nitrogen oxides, and VOCs, are needed to support regional air quality
      monitoring. Components of the SHARP campaign measured these species in several
      different ways, each with their own potential for systematic errors and
      differences in vehicle fleets sampled. Comparisons between data sets suggest that
      differences in sampling place and time may result in quite different emission
      factors, while also showing that different vehicle mixes can yield surprisingly
      similar emission factors.

PMID- 25976484
TI  - Modeling of time-resolved light extinction and its applications to visibility
      management in the Lower Fraser Valley of British Columbia, Canada.
AB  - Fine particulate matter (PM2.5) is the dominant cause of atmospheric visibility
      degradation in the Lower Fraser Valley (LFV) of British Columbia, where poor
      visibility due to air pollution is of concern. The spatial coverage of the
      current LFV visibility monitoring network is relatively low, with large parts of
      the airshed not being represented. Given the desire on the part of local and
      regional governments to manage visibility in the LFV airshed, the development of
      a method that allows near real-time estimation of 1-hr light extinction data from
      the dense network of PM measurements would be highly beneficial. This paper
      describes a simple linear algorithm, developed using the Hybrid method, to
      estimate near real-time 1-hr total light extinction at four monitoring sites in
      the LFV. Model inputs include ambient hourly PM2.5, NO2, relative humidity
      measurements, and historical monthly-averaged aerosol composition. The results
      indicate that the developed model can provide relatively accurate and time
      resolved estimates of extinction in regions where visibility is not being
      monitored, thus extending the spatial coverage of the regional visibility
      monitoring network. The model was also applied to a number of policy-related
      scenarios to inform visual air quality management in the study area. Results
      indicated that in order to achieve a perceptible improvement (1.0 deciview)
      relative to baseline average visibility conditions in the LFV airshed, average
      ambient PM2.5 concentration would have to decrease by 17% from baseline
      conditions. Furthermore, to achieve a 20% increase in the number of daylight
      hours with "excellent" visibility, average PM2.5 would need to be reduced by 30%.
      Model simulations also indicated that "across-the-board" emission reduction
      policies would result in greater improvements for the "worst 20%" visibility
      conditions than for the "best 20%" conditions, suggesting that reducing the
      number of "poor" visibility days would be easier than improving the number of
      "excellent" visibility days. IMPLICATIONS: This study describes the development
      of a model using standard air quality monitoring data (PM2.5, NO2, relative
      humidity, and PM speciation profiles) to provide near real-time estimates of time
      resolved extinction in regions where direct optical monitoring is not available.
      Applications of the model include extension of spatial coverage of a visibility
      network, testing various air quality scenarios to inform visibility management,
      and as a tool for setting visual air quality standards in impacted airsheds.

PMID- 25976485
TI  - Rural domestic waste management in Zhejiang Province, China: Characteristics,
      current practices, and an improved strategy.
AB  - Lack of access to adequate sanitation facilities has serious health implications
      for rural dwellers and can degrade the ecosystems. This study offers a
      systemantic and quantitative overview of historical data on rural domestic waste
      (RDW) production and past and current management practices in a prototype region
      in China, where rural areas are undergoing rapid urbanization and are confronted
      with great environmental challenges associated with poor RDW management
      practices. The results indicate that RDW is characterized with a large fraction
      of kitchen waste (42.9%) and high water content (53.4%). The RDW generation
      (RDWG) per capita between 2012 and 2020 is estimated to increase from 0.68 to
      1.01 kg/d-cap. The Hill 1 model is able to adequately simulate/project the
      population growth in a rural area from 1993 to 2020. The annual RDWG in the
      region is estimated to double from 6,033,000 tons/year in 2008 to 12,030,000
      tons/year by 2020. By comparing three RDW management scenarios based on the life
      cycle inventory approach and cost-benefit analysis, it is strongly recommended
      that the present Scenario 2 (sanitary landfill treatment) be upgraded to Scenario
      3 (source separation followed by composting and landfill of RDW) to significantly
      reduce the ecological footprint and to improve the cost-effectiveness and long
      term sustainability. IMPLICATIONS: Rural domestic waste (RDW) is affecting 720
      million people in China and more than 3221 million people worldwide.
      Consequently, handling and disposal of RDW have serious health implications to
      rural dwellers and the ecosystems. This study offers a systemantic and
      quantitative overview and analysis of historical data on RDW production and
      management practices in a prototype region in China, which is confronted with
      great environmental challenges associated with RDW. Then we predict future
      production of RDW and propose a sustainable RDW management strategy, which holds
      the promise of greatly mitigating the mounting environmental pressure associated
      with RDW and provides science-based guidance for decision makers and
      practitioners for assuring rapid yet "green" economic development.

PMID- 25976486
TI  - Optimization of multipollutant air quality management strategies: A case study
      for five cities in the United States.
AB  - Developing regional air quality management strategies is a difficult task because
      formation of air pollutants is interdependent and air quality at different
      locations may have different responses to emissions from common sources. We
      developed an optimization-based model, OPtimal integrated Emission Reduction
      Alternatives (OPERA), which allows for identifications of least-cost control
      strategies for attaining multipollutant air quality targets at multiple locations
      simultaneously. To implement OPERA, first, sensitivities of air quality to
      precursor emission changes are quantified. Second, cost functions of emission
      reductions are estimated using a cost analysis tool that includes a pool of
      available control measures. The third step is to determine desired reductions in
      concentrations of air pollutants. The last step is to identify the optimal
      control strategies by minimizing costs of emission controls using the
      sensitivities of air pollutants to emission changes, cost functions, and
      constraints for feasible emission reduction ratios. A case study that
      investigates ozone and PM2.5 air quality in the summer of 2007 for five major
      cities in the eastern United States is presented in this paper. The results of
      the OPERA calculations show that reductions in regional NOx and VOC as well as
      local primary PM2.5 emissions were more cost-effective than SO2 controls for
      decreasing ozone and total PM2.5 concentrations in the summer of 2007. This was
      because reductions in SO2 emissions would only decrease PM2.5 concentrations, and
      reductions in primary PM2.5 emissions were more cost-effective than SO2 emission
      controls. IMPLICATIONS: We developed an optimization-based model, OPtimal
      integrated Emission Reduction Alternatives (OPERA), which allows for
      identification of least-cost emission control strategies for attaining
      multipollutant air quality targets at multiple locations simultaneously. A major
      strength of OPERA is its flexibility, which allows for changes in air quality
      regulations, involving agencies, study regions, and so on, to be readily
      incorporated. Overall, it has been demonstrated that OPERA is useful in
      developing least-cost emission control strategies for achieving multipollutant
      air quality targets at multiple locations simultaneously and could be useful for
      policymakers developing integrated air quality management plans.

PMID- 25976487
TI  - Leaching assessments of toxic metals in waste plasma display panel glass.
AB  - The plasma display panel (PDP) is rapidly becoming obsolete, contributing in
      large amounts to the electronic waste stream. In order to assess the potential
      for environmental pollution due to hazardous metals leached from PDP glass,
      standardized leaching procedures, chemical speciation assessments, and
      bioavailability tests were conducted. According to the Toxicity Characteristic
      Leaching Procedure (TCLP), arsenic in back glass was present at 4.46 +/- 0.22
      mg/L, close to its regulation limit of 5 mg/L. Zn is not available in the TCLP,
      but its TCLP leaching concentration in back glass is 102.96 +/- 5.34 mg/L. This
      is because more than 90% of Zn is in the soluble and exchangeable and carbonate
      fraction. We did not detect significant levels of Ag, Ba, or Cu in the TCLP
      leachate, and the main fraction of Ag and Ba is residual, more than 95%, while
      the fraction distribution of Cu changes SEP by SEP. Ethylenediamine tetraacetic
      acid (EDTA)- and diethylenetriamine pentaacetic acid (DTPA)-extractable Ag, As,
      Ba, Cu, Zn, and Ni indicate a lower biohazards potential. These results show
      that, according to the EPA regulations, PDP glass may not be classified as
      hazardous waste because none of the metals exceeded their thresholds in PDP
      leachate. However, the concentrations of As and Zn should be lowered in the
      manufacturing process and finished product to avoid potential pollution problems.
      IMPLICATIONS: The plasma display panel is rapidly becoming obsolete because of
      the liquid crystal display. In this study, the leachability of heavy metals
      contained in the waste plasma display panel glass was first examined by
      standardized leaching tests, typical chemical speciation assessments, and
      bioavailability tests, providing fundamental data for waste PDP glass recovery,
      recycling, and reuse.

PMID- 25976488
TI  - Temperature effects on particulate emissions from DPF-equipped diesel trucks
      operating on conventional and biodiesel fuels.
AB  - Emissions tests were conducted on two medium heavy-duty diesel trucks equipped
      with a particulate filter (DPF), with one vehicle using a NOx absorber and the
      other a selective catalytic reduction (SCR) system for control of nitrogen oxides
      (NOx). Both vehicles were tested with two different fuels (ultra-low-sulfur
      diesel [ULSD] and biodiesel [B20]) and ambient temperatures (70oF and 20oF),
      while the truck with the NOx absorber was also operated at two loads (a heavy
      weight and a light weight). The test procedure included three driving cycles, a
      cold start with low transients (CSLT), the federal heavy-duty urban dynamometer
      driving schedule (UDDS), and a warm start with low transients (WSLT). Particulate
      matter (PM) emissions were measured second-by-second using an Aethalometer for
      black carbon (BC) concentrations and an engine exhaust particle sizer (EEPS) for
      particle count measurements between 5.6 and 560 nm. The DPF/NOx absorber vehicle
      experienced increased BC and particle number concentrations during cold starts
      under cold ambient conditions, with concentrations two to three times higher than
      under warm starts at higher ambient temperatures. The average particle count for
      the UDDS showed an opposite trend, with an approximately 27% decrease when
      ambient temperatures decreased from 70oF to 20oF. This vehicle experienced
      decreased emissions when going from ULSD to B20. The DPF/SCR vehicle tested had
      much lower emissions, with many of the BC and particle number measurements below
      detectable limits. However, both vehicles did experience elevated emissions
      caused by DPF regeneration. All regeneration events occurred during the UDDS
      cycle. Slight increases in emissions were measured during the WSLT cycles after
      the regeneration. However, the day after a regeneration occurred, both vehicles
      showed significant increases in particle number and BC for the CSLT drive cycle,
      with increases from 93 to 1380% for PM number emissions compared with tests
      following a day with no regeneration. IMPLICATIONS: The use of diesel particulate
      filters (DPFs) on trucks is becoming more common throughout the world.
      Understanding how DPFs affect air pollution emissions under varying operating
      conditions will be critical in implementing effective air quality standards. This
      study evaluated particulate matter (PM) and black carbon (BC) emissions with two
      DPF-equipped heavy-duty diesel trucks operating on conventional fuel and a
      biodiesel fuel blend at varying ambient temperatures, loads, and drive cycles.

PMID- 25976489
TI  - The effects of emission control strategies on light-absorbing carbon emissions
      from a modern heavy-duty diesel engine.
AB  - Control of atmospheric black carbon (BC) and brown carbon (BrC) has been proposed
      as an important pathway to climate change mitigation, but sources of BC and BrC
      are still not well understood. In order to better identify the role of modern
      heavy-duty diesel engines on the production of BC and BrC, emissions from a heavy
      duty diesel engine operating with different emission control strategies were
      examined using a source dilution sampling system. The effect of a diesel
      oxidation catalyst (DOC) and diesel particulate filter (DPF) on light-absorbing
      carbon (LAC) was evaluated at three steady-state engine operation modes: idle,
      50% speed and load, and 100% speed and load. LAC was measured with four different
      engine configurations: engine out, DOC out, DPF out, and engine out with an
      altered combustion calibration. BC and BrC emission rates were measured with the
      Aethalometer (AE-31). EC and BC emission rates normalized to the mass of
      CO2emitted increased with increasing engine speed and load. Emission rates
      normalized to brake-specific work did not exhibit similar trends with speed and
      load, but rather the highest emission rate was measured at idle. EC and OC
      emissions were reduced by 99% when the DOC and DPF architecture was applied. The
      application of a DPF was equally effective at removing 99% of the BC fraction of
      PM, proving to be an important control strategy for both LAC and PM. BC emissions
      were unexpectedly increased across the DOC, seemingly due to a change aerosol
      optical properties. Removal of exhaust gas recirculation (EGR) flow due to
      simulated EGR cooler failure caused a large increase in OC and BrC emission rates
      at idle, but had limited influence during high load operation. LAC emissions
      proved to be sensitive to the same control strategies effective at controlling
      the total mass of diesel PM. IMPLICATIONS: In the context of black carbon
      emissions, very small emission rates of brown carbon were measured over a range
      of control technologies and engine operating conditions. During specific idle
      engine operation without EGR and adjusted fueling conditions, brown carbon can be
      formed in significant amounts, requiring careful management tactics. Control
      technologies for particulate matter are very effective for light-absorbing
      carbon, reducing black carbon emissions to near zero for modern engines equipped
      with a DPF. Efforts to control atmospheric brown carbon need to focus on other
      sources other than modern diesel engines, such as biomass burning.

PMID- 25976490
TI  - Esophageal variceal bleeding in hospitalized patients with cirrhosis.
AB  - Esophageal variceal bleeding (EVB) is a frequent complication in cirrhotic
      patients resulting in considerable mortality and morbidity. The aim of this study
      was to investigate the occurrence, impact, and trends of EVB in hospitalized
      cirrhotic patients on a nationwide level in the United States. We interrogated
      data from the Nationwide Inpatient Sample from 2002 to 2012. Utilizing
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes, we analyzed hospital discharges for cirrhosis and related EVB in adult
      patients. EVB in cirrhotic patients was independently associated with overall
      worse outcomes with respect to in-hospital mortality (10% vs 5%; P < 0.01) and
      hospital charges (median $41,000 vs $26,000; P < 0.01). In the period from 2002
      to 2012, the number of cirrhosis-related hospitalizations increased from 337,956
      to 570,220 (P < 0.01). Concurrently, the incidence of EVB in hospitalized
      cirrhotic patients declined from 8.60% to 5.78%, with an overall decreased trend
      (P < 0.01). The decline in the rate of EVB in hospitalized cirrhotic patients
      from 2002 to 2012 likely reflects the effectiveness of primary and secondary
      prophylaxis.

PMID- 25976492
TI  - Monomeric and oligomeric flavan-3-ols and antioxidant activity of leaves from
      different Laurus sp.
AB  - The phenolic profile and antioxidant activity of three endemic Laurus sp. from
      Portugal were analysed. Dried leaves of L. nobilis L., L. azorica (Seub.) Franco,
      and L. novocanariensis Rivas Mart., Lousa, Fern. Prieto, E. Dias, J. C. Costa &
      C. Aguiar, collected in the mainland and in the Azores and Madeira archipelagos,
      respectively, were used to prepare different extracts (aqueous, ethanolic and
      hydroalcoholic). They were studied regarding their DPPH scavenging activity,
      total phenolic and flavonoid contents, and the main phenolic compounds were
      identified by HPLC-DAD-ESI-MS/MS. Total flavonoid contents were 30.1, 46.3, and
      36.7 mg of epicatechin equivalents per g of sample (dry weight) for L. nobilis,
      L. azorica and L. novocanariensis, respectively. Epicatechin was the major
      compound, representing ~12.1% of total flavan-3-ols in L. nobilis, ~25.6% in L.
      azorica, and ~19.9% in L. novocanariensis. Although all samples presented a
      similar phenolic profile, significant differences were observed in their total
      contents and antioxidant activity.

PMID- 25976493
TI  - Proton beam therapy: the next disruptive innovation in healthcare?

PMID- 25976494
TI  - Republished: Antiplatelet therapy for secondary prevention of coronary artery
      disease.
AB  - The choice and duration of antiplatelet therapy for secondary prevention of
      coronary artery disease (CAD) is determined by the clinical context and treatment
      strategy. Oral antiplatelet agents for secondary prevention include the cyclo
      oxygenase-1 inhibitor aspirin, and the ADP dependent P2Y12 inhibitors
      clopidogrel, prasugrel and ticagrelor. Aspirin constitutes the cornerstone in
      secondary prevention of CAD and is complemented by clopidogrel in patients with
      stable CAD undergoing percutaneous coronary intervention. Among patients with
      acute coronary syndrome, prasugrel and ticagrelor improve net clinical outcome by
      reducing ischaemic adverse events at the expense of an increased risk of bleeding
      as compared with clopidogrel. Prasugrel appears particularly effective among
      patients with ST elevation myocardial infarction to reduce the risk of stent
      thrombosis compared with clopidogrel, and offered a greater net clinical benefit
      among patients with diabetes compared with patients without diabetes. Ticagrelor
      is associated with reduced mortality without increasing the rate of coronary
      artery bypass graft (CABG)-related bleeding as compared with clopidogrel. Dual
      antiplatelet therapy should be continued for a minimum of 1 year among patients
      with acute coronary syndrome irrespective of stent type; among patients with
      stable CAD treated with new generation drug-eluting stents, available data
      suggest no benefit to prolong antiplatelet treatment beyond 6 months.

PMID- 25976495
TI  - Memories of the workhouse.

PMID- 25976496
TI  - Republished: Importance of carcinoma-associated fibroblast-derived proteins in
      clinical oncology.
AB  - Carcinoma-associated fibroblast (CAF) as prominent cell type of the tumour
      microenvironment has complex interaction with both the cancer cells and other non
      neoplastic surrounding cells. The CAF-derived regulators and extracellular matrix
      proteins can support cancer progression by providing a protective
      microenvironment for the cancer cells via reduction of chemotherapy sensitivity.
      On the other hand, these proteins may act as powerful prognostic markers as well
      as potential targets of anticancer therapy. In this review, we summarise the
      clinical importance of the major CAF-derived signals influencing tumour behaviour
      and determining the outcome of chemotherapy. 

PMID- 25976497
TI  - Primary cervical choriocarcinoma during viable intrauterine pregnancy.
AB  - A 31-year-old multigravida woman at 27 weeks' gestation was admitted with vaginal
      bleeding and a hypervascular mass near the cervix on ultrasonography. After
      discharge with improvement, she was readmitted the next day for uncontrolled,
      heavy vaginal bleeding and underwent emergency cesarean section at 29 weeks'
      gestation. A 3-cm friable mass found near the cervix was removed surgically; this
      lesion was shown to be primary cervical choriocarcinoma. On the 17th
      postoperative day the patient underwent total abdominal hysterectomy with
      preservation of both ovaries and biopsy was performed on the right ovary. The
      International Federation of Gynecology and Obstetrics (FIGO) stage was I and her
      World Health Organization prognostic score was 9, representing high risk. The
      patient received three rounds of chemotherapy until achieving three consecutive
      normal human chorionic gonadotropin levels with two additional courses to address
      risk of relapse. DNA genotyping on short tandem repeat polymorphism confirmed the
      gestational choriocarcinoma.

PMID- 25976498
TI  - X-ray exposure in utero and school performance: a population-based study of X-ray
      pelvimetry.
AB  - AIM: To investigate the association between exposure to ionising radiation from
      pelvimetric examinations in utero and school performance. MATERIAL AND METHODS:
      This was a population-based cohort study comprising 46,066 children born in the
      county of Ostergotland, Sweden, from 1980 through 1990. Through record linkage
      between Swedish registers, children exposed in utero to X-ray pelvimetry
      examination were compared to other children born in the same county during the
      study period, as well as to their unexposed siblings. Outcome variable was
      primary school grades, expressed in centiles and calculated through linear
      regression. RESULTS: In the univariate analysis, children exposed to X-ray
      pelvimetry in utero had higher school grades compared to unexposed children
      (point estimate 3 centiles, 95% confidence interval [CI]: 1.5 to 4.6). When sex,
      mother's education and income, birth order, and birth position were included in
      the analysis; however, the difference was reduced and the association was no
      longer statistically significant (PE 1.4, 95% CI: -0.1 to 2.8). Comparing exposed
      children with their siblings showed no statistical difference in univariate
      analysis or in multivariate analysis. CONCLUSION: No suggestion was found of a
      negative effect on school performance from in utero exposure of diagnostic X-ray
      pelvimetry.

PMID- 25976499
TI  - Non-contrast-enhanced MR angiography for detecting arteriovenous fistula
      dysfunction in haemodialysis patients.
AB  - AIM: To assess the diagnostic value of non-contrast-enhanced magnetic resonance
      angiography (NCE-MRA), using time-of-flight and black-blood MRA, in the
      evaluation of arteriovenous fistulas in haemodialysis patients in comparison to
      multidetector computed tomography angiography (MDCTA). MATERIAL AND METHODS: NCE
      MRA and MDCTA were performed on the same day in 21 patients on maintenance
      haemodialysis with dysfunctional arteriovenous fistulas. The fistulas included
      three segments: arterial inflow, anastomosis, and venous outflow. Two experienced
      observers, who were blinded to the results of the NCE-MRA, recorded in consensus
      the significant stenoses (>=50%) seen on CTA. Two other experienced observers,
      unaware of the results of CTA, independently recorded significant stenoses
      (>=50%) in the NCE-MRA. The sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of NCE-MRA were calculated, with MDCTA as
      the standard reference. RESULTS: Sixty-three vascular segments in the 21 patients
      were clearly displayed. For the two observers of NCE-MRA, the accuracy was 98%
      and 95.4%; sensitivity 96.4% and 96.4%; specificity 97.1% and 94.3%; positive
      predictive value 96.4% and 93.1%; and, negative predictive value 97.1% and 97.1%.
      Inter-/intra-observer agreement for detecting stenosis was excellent for NCE-MRA,
      with a weighted kappa of 0.968 (95% confidence interval [CI], 0.874-1) and 0.936
      (95% CI, 0.848-1). CONCLUSION: Non-contrast-enhanced MRA, using time-of-flight
      and black-blood MRA, is a reproducible and reliable imaging technique for
      detecting >=50% stenosis in dysfunctional haemodialysis arteriovenous fistulas.

PMID- 25976501
TI  - Human Platelet Polymorphism can be a genetic marker associated with HIV/HCV
      coinfection.
AB  - To evaluate the associations of HPA polymorphisms -1, -3, and -5 with HIV/HCV
      coinfection were included in this study 60 HIV/HCV-coinfected patients from the
      Sao Paulo State health service centers. Data reported by Verdichio-Moraes et al.
      (2009: J. Med Virol 81:757-759) were used as the non-infected and HCV
      monoinfected groups. Human Platelet Polymorphism genotyping was performed in 60
      Patients co-infected with HIV/HCV by PCR-SSP or PCR-RFLP. HIV subtyping and HCV
      genotyping was performed by RT-PCR followed sequencing. The data analyses were
      performed using the chi2 test or Fisher's Exact Test and the logistic regression
      model. Patients coinfected with HIV/HCV presented HCV either genotype 1 (78.3%)
      or non-1 (21.7%) and HIV either subtype B (85.0%) or non-B (15%). The Human
      Platelet Polymorphism-1a/1b genotype was more frequent (P < 0.05) in HIV/HCV
      coinfection than in HCV monoinfection and the allelic frequency of Human Platelet
      Polymorphism-5b in the Patients coinfected with HIV/HCV was higher (P < 0.05)
      than in HCV monoinfected cases and non-infected individuals. These data suggest
      that the presence of specific HPA allele on platelets could favor the existence
      of coinfection. On the other hand, Human Platelet Polymorphism-5a/5b was more
      frequent (P < 0.05) in HIV/HCV coinfected and HCV monoinfected groups than in the
      non-infected individuals, suggesting that this platelet genotype is related to
      HCV infection, regardless of HIV presence. Results suggest that the Human
      Platelet Polymorphism profile in HIV/HCV coinfected individuals differs from the
      one of both HCV monoinfected and non-infected population. So, the Human Platelet
      Polymorphism can be a genetic marker associated with HIV/HCV coinfection.

PMID- 25976500
TI  - Feasibility of liver graft procurement with donor gallbladder preservation in
      living donor liver transplantation.
AB  - OBJECTIVE: Cholecystectomy is routinely performed at most transplant centers
      during living donor liver transplantation (LDLT). This study was performed to
      evaluate the feasibility of liver graft procurement with donor gallbladder
      preservation in LDLT. METHODS: Eighty-nine LDLTs (from June 2006 to Dec 2012)
      were retrospectively analyzed at our hospital. The surgical approach for liver
      graft procurement with donor gallbladder preservation was assessed, and the
      anatomy of the cystic artery, the morphology and contractibility of the preserved
      gallbladder, postoperative symptoms, and vascular and biliary complications were
      compared among donors with or without gallbladder preservation. RESULTS: Twenty
      eight donors (15 right and 13 left-liver grafts) successfully underwent liver
      graft procurement with gallbladder preservation. Among the 15 right lobectomy
      donors, for 12 cases (80.0 %) the cystic artery originated from right hepatic
      artery. From the left hepatic artery and proper hepatic artery accounted for 6.7
      % (1/15), respectively. Postoperative symptoms among these 28 donors were slight,
      although donors with cholecystectomy often complained of fatty food aversion,
      dyspepsia, and diarrhea during an average follow-up of 58.6 (44-78) months. The
      morphology and contractibility of the preserved gallbladders were comparable with
      normal status; the rate of contraction was 53.8 and 76.7 %, respectively, 30 and
      60 min after ingestion of a fatty meal. Biliary and vascular complications among
      donors and recipients, irrespective of gallbladder preservation, were not
      significantly different. CONCLUSIONS: These data suggest that for donors
      compliant with anatomical requirements, liver graft procurement with gallbladder
      preservation for the donor is feasible and safe. The preserved gallbladder was
      assessed as functioning well and postoperative symptoms as a result of
      cholecystectomy were significantly reduced during long-term follow-up.

PMID- 25976502
TI  - MicroRNA-370 inhibits the progression of non-small cell lung cancer by
      downregulating oncogene TRAF4.
AB  - Lung cancer is the leading cause of cancer-related deaths, of which most can be
      attributed to non-small cell lung cancer (NSCLC). microRNAs (miRNAs) are a group
      of small non-coding RNAs that focus on post-transcriptional modification. The
      present study aimed to investigate the role and function of microRNA-370 (miR
      370) in NSCLC and explore the underlying functional mechanisms. We found that miR
      370 was significantly downregulated in the tumor tissues of NSCLC patients as
      well as in NSCLC cell lines. Overexpression of miR-370 by infection of
      recombinant lentivirus markedly inhibited cell proliferation and promoted cell
      apoptosis of NSCLC cells. In addition, in vivo tumor formation of NSCLC cells was
      decreased by miR-370 overexpression. Through bioinformatic analysis, we found
      that tumor necrosis factor receptor-associated factor 4 (TRAF4), an oncogene as
      previously reported, was predicted as a putative target gene of miR-370. The
      direct targeting relationship between miR-370 and the 3'-untranslated region was
      validated by dual-luciferase reporter assay. Furthermore, overexpression of miR
      370 downregulated the protein expression of TRAF4 in the NSCLC cells. Moreover,
      the growth inhibitory effect of miR-370 overexpression on NSCLC cells was
      abrogated by TRAF4 overexpression. In conclusion, our results suggest that miR
      370 plays an important role in NSCLC by regulating TRAF4 and may be a potential
      target for the treatment of NSCLC.

PMID- 25976503
TI  - MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells
      by targeting FZD7.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles
      in tumorigenesis and tumor progression through regulation of gene expression.
      Earlier, miR-142-3p was shown to decreased in cervical cancer cells; here; we
      explore the biological functional role of miR-142-3p and underlying mechanism in
      cervical cancer cells. We first detected the expression of miR-142-3p in six
      human cervical cancer cell lines and chose HeLa and SiHa cells for functional
      studies. By gain and loss of function experiments, we showed that overexpression
      of miR142-3p resulted in downregulation of Frizzled7 receptor (FZD7) and
      inhibited proliferation and invasion in HeLa and SiHa cells, whereas miR142-3p
      inhibitor-transfected cells showed reduced FZD7 expression and increased invasion
      capacity. In addition, we demonstrated that FZD7 was a direct target of miR-142
      3p by dual luciferase assay and Western blot analysis. Overexpression of FZD7
      expression was able to reverse the inhibitory effects induced by miR-142-3p.
      Taken together, miR-142-3p functions tumor suppressive effects in cell
      proliferation and invasion in cervical cancer cells, suggesting a potential
      therapeutic approach for cervical cancer.

PMID- 25976504
TI  - Gene profiling and circulating tumor cells as biomarker to prognostic of patients
      with locoregional breast cancer.
AB  - The gene profile of primary tumors, as well as the identification of circulating
      tumor cells (CTCs), can provide important prognostic and predictive information.
      In this study, our objective was to perform tumor gene profiling (TGP) in
      combination with CTC characterization in women with nonmetastatic breast cancer.
      Biological samples (from peripheral blood and tumors) from 167 patients diagnosed
      with stage I, II, and III mammary carcinoma, who were also referred for
      adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters:
      (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in
      the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse
      transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the
      expression of 21 genes in paraffin-embedded tissue samples by quantitative
      multiplex RT-PCR with the Plexor(r) system. We observed a statistically
      significant correlation between the progression-free interval (PFI) and the
      clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of
      hormone receptors in the tumor (p = 0.0432). We observed no correlation between
      the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC
      fraction prior to the start of treatment or in the two following readouts.
      Multivariate analysis revealed that only the TGP score significantly correlated
      with the PFI (p = 0.029247). The TGP is an important prognostic variable for
      patients with locoregional breast cancer. The presence of CTCs adds no prognostic
      value to the information already provided by the TGP.

PMID- 25976505
TI  - The predicting value of postoperative body temperature on long-term survival in
      patients with rectal cancer.
AB  - This study aimed to assess the association between postoperative body temperature
      and prognosis in patients with rectal cancer. Five hundred and seven patients
      with stage I to III rectal cancers were enrolled in the current study. Basal body
      temperature (BBT, measured at 6 am) and maximal body temperature (MBT) on each
      day after surgery were analyzed retrospectively. Patients were divided into two
      equal groups according to the median of BBT and MBT at each day. The primary end
      points were disease-free survival (DFS) and overall survival (OS). The univariate
      and multivariate analyses showed that patients with low D0-MBT (<37.4  degrees C)
      had lower 3-year DFS [adjusted hazard ratio (HR) 1.56 (95 % CI 1.08-2.24, P =
      0.017)] as well as OS [adjusted HR 1.72 (95 % CI 1.05-2.82, P = 0.032)] rate as
      compared to those with high D0-MBT (>37.4  degrees C). In the subset of 318
      patients with T3 stage tumor and the subgroup of 458 patients without blood
      transfusion as well, low D0-MBT continues to be an independent predictor of
      DFS/OS with an adjusted HR equal to 1.48 (95 % CI 1.02-2.24, P = 0.046)/1.68 (95
      % CI 1.04-2.99, P = 0.048) and 1.45 (95 % CI 1.02-2.13, P = 0.048)/1.59 (95 % CI
      1.01-2.74, P = 0.049), respectively. In addition, we found that patients have
      higher risk of 1-year recurrence if those were exhibiting low preoperative BBT
      (<36.6  degrees C) (17 vs. 10 %, P = 0.034). Low body temperature (D0-MBT < 37.4 
      degrees C) after surgery was an independent predictor of poor survival outcomes
      in patients with rectal cancer.

PMID- 25976506
TI  - Endoplasmic reticulium protein profiling of heat-stressed Jurkat cells by one
      dimensional electrophoresis and liquid chromatography tandem mass spectrometry.
AB  - Proteomic study on membrane-integrated proteins in endoplasmic reticulum (ER)
      fractions was performed. In this study, we examined the effects of heat stress on
      Jurkat cells. The ER fractions were highly purified by differential
      centrifugation with sodium carbonate washing and acetone methanol precipitations.
      The ER membrane proteins were separated by one dimensional electrophoresis (1
      DE), and some of the protein bands changed their abundance by heat stress, 12 of
      the 14 bands containing 40 and 60 ribosomal proteins whose expression level were
      decreased, on the contrary, 2 of the 14 bands containing ubiquitin and eukaryotic
      translation initiation factor 3 were increased. Heat treatment of human Jurkat
      cells led to an increase in the phosphorylation of PERK and eIF2alpha within 30
      min of exposure. This was followed by an increase in the expression of the GRP78.
      Protein ubiquitination and subsequent degradation by the proteasome are important
      mechanisms regulating cell cycle, growth and differentiation, the result showed
      that heat stress enhanced ubiquitination modification of the microsomal proteins.
      The data of this study strongly suggest that heat treatment led to a significant
      reduction in protein expression and activated UPR, concomitant with protein
      hyperubiqutination in ER. 

PMID- 25976507
TI  - Development and characterization of conducting polymer nanoparticles for
      photodynamic therapy in vitro.
AB  - Conducting polymer nanoparticles (CPNPs), composed of the conducting polymer
      poly[2-methoxy-5-(2-ethylhexyl-oxy)-p-phenylenevinylene] (MEH-PPV) were studied
      for applications in biophotonics and therapeutics. The extent of cellular uptake,
      cytotoxicity, and effectiveness of these nanoparticles in photodynamic therapy
      (PDT) was investigated for four cell lines, namely TE-71, MDA-MB-231, A549 and
      OVCAR3. Confocal fluorescence imaging and flow cytometry show that CPNPs are
      taken up only in limited quantities by TE-71, while they are taken up extensively
      by the cancer cell lines. The uptake among the cancer cell lines was observed to
      vary with cell line, with CPNPs uptake increasing from MDA-MB-231 to A549 to
      OVCAR3. Fluorescence imaging experiments show that the CPNPs have high brightness
      and appear stable in the intracellular environment. No cytotoxicity of non
      photoactivated CPNPs (in dark) was observed from MTT assay. After completion of
      PDT, the quantitative data on cell viability suggest that cell death scales
      across the cell lines with CPNP uptake, is light dose dependent, and is complete
      for OVCAR3. In addition, for OVCAR3 apoptotic cell death is observed after PDT.
      The reported work illustrates the potential of the intrinsically fluorescent and
      photoactivateable CPNPs for application in biophotonics and therapeutics.

PMID- 25976508
TI  - Assessment of sequential combination of 5-fluorouracil-loaded-chitosan
      nanoparticles and ALA-photodynamic therapy on HeLa cell line.
AB  - BACKGROUND: Natural polymers are used as components of nanoparticles (NPs) for
      drug delivery, as they provide targeted, sustained release and biodegradability.
      The purpose of this study was to increase the efficacy of the photodynamic
      therapy (PDT) by the combination of 5-aminolevulinic acid (ALA) with 5
      fluorouracil-loaded-chitosan-nanoparticles (5-Fu-CNPs). METHODS: Nanoparticles
      based on chitosan (CNPs) were synthesized by the ionic crosslinking method via
      the TPP addition. 5-Fluorouracil (5-Fu), a first-line anticancer drug, was loaded
      into these 5Fu-CNPs, and they were assayed as controlled delivery formulation.
      HeLa cells were incubated in the presence of 5Fu-CNPs for 24h, next ALA was added
      to the culture medium and 4h later, to complete the PDT, light irradiation took
      place. Analysis of cell viability, reactive oxygen species (ROS) production,
      observation of the apoptosis by fluorescence microscopy followed by analysis of
      caspase-3 activity were carried out. RESULTS: Spherical 5Fu-CNPs with a mean
      diameter of 324+/-43nm, were successfully synthesized and characterized by TEM
      and DLS. 5-Fu incorporation was achieved successfully (12.3MUg 5Fu/mg CNP) and
      the maximum 5-Fu release took place at 2h. The combined administration of 5Fu
      CNPs and PDT mediated by ALA (ALA-PDT) led to an improved efficacy of the
      antineoplastic treatment by generation of great cytotoxicity inducted through an
      increased ROS production. HeLa cells were destroyed by apoptosis through
      activation of caspase pathway. CONCLUSIONS: This study proves that combination
      therapy (photodynamic "ALA"+chemical "5-Fu"+immunoadjuvant "chitosan") may be an
      effective approach for the treatment of cancer.

PMID- 25976509
TI  - Cytotoxicity and intracellular fate of PLGA and chitosan-coated PLGA
      nanoparticles in Madin-Darby bovine kidney (MDBK) and human colorectal
      adenocarcinoma (Colo 205) cells.
AB  - Polymeric nanoparticles (NPs) are known to facilitate intracellular uptake of
      drugs to improve their efficacy, with minimum bioreactivity. The goal of this
      study was to assess cellular uptake and trafficking of PLGA NPs and chitosan
      (Chi)-covered PLGA NPs in Madin-Darby bovine kidney (MDBK) and human colorectal
      adenocarcinoma (Colo 205) cells. Both PLGA and Chi-PLGA NPs were not cytotoxic to
      the studied cells at concentrations up to 2500 MUg/mL. The positive charge
      conferred by the chitosan deposition on the PLGA NPs improved NPs uptake by MDBK
      cells. In this cell line, Chi-PLGA NPs colocalized partially with early endosomes
      compartment and showed a more consistent perinuclear localization than PLGA NPs.
      Kinetic uptake of PLGA NPs by Colo 205 was slower than that by MDBK cells,
      detected only at 24 h, exceeding that of Chi-PLGA NPs. This study offers new
      insights on NP interaction with target cells supporting the use of NPs as novel
      nutraceuticals/drug delivery systems in metabolic disorders or cancer therapy.
      (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3599-3611,
      2015. 

PMID- 25976510
TI  - 'Allowing the right' and its currency in managing drug stigma in Greece.
AB  - BACKGROUND: Evidence suggests that problem drug users are still subject to high
      levels of stigmatization. In countries, like Greece, where families occupy a
      central position and honour is collectively attained, secondary drug stigma is
      also highly prevalent. However, little is known about how drug users and their
      families manage drug stigma in the specific cultural milieu that makes up Greece.
      This article presents findings from a qualitative study exploring how drug stigma
      both manifests itself and is managed by drug users and parents in the context of
      Greek familial culture. METHODS: The study was conducted in two state drug
      agencies in Thessaloniki - Greece and involved the participation of 40 problem
      drug users (PDU) (23 male/17 female) and 8 parents of PDU. Qualitative, in-depth,
      interviews were used to collect narrative accounts about experiences of managing
      addiction, drug stigma and secondary stigma in the Greek parental home. RESULTS:
      'Allowing the right' - broadly understood as referring to passing to others
      information which might devalue a person and consequently that person's family -
      is discussed in terms of drug stigma management in Greece. We highlight how this
      culturally specific notion can be viewed as an active strategy adopted by both
      individual drug users and parents of PDU to manage stigmatization by illustrating
      the various way in which not 'allowing the right' was described by participants,
      including drug problem discovery or disclosure and subsequent management of drug
      using careers and drug stigma within the Greek family context. CONCLUSION: Given
      the significance of the cultural notion of 'allowing the right' in the trajectory
      of drug use amongst PDU and more particularly in stigma management and secondary
      stigma management, the paper highlights the need for further research into the
      field in Greece. The need for targeted culturally specific and culturally
      relevant interventions aimed at reducing drug stigma is also highlighted in
      relation to both policy and practice.

PMID- 25976511
TI  - Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe.
AB  - Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and
      an anaesthetic. Recent concerns have arisen around the illicit use of fentanyl
      and its analogues in a number of European countries, linked to their high potency
      and associated risk of fatal overdose. Evidence has been emerging from Estonia
      for over a decade of entrenched patterns of fentanyl use, including injection of
      the drug and hundreds of overdose deaths. More recently, reports indicate that
      both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for
      heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin
      shortages. In addition, Germany, Finland and the United Kingdom, reported new
      outbreaks of fentanyl-related deaths. This combination of increasing mortality
      data alongside law enforcement intelligence suggesting both diversion and illicit
      production of fentanyls, prompted wider investigation using a targeted multi
      source data collection exercise and analysis. This identified that in the
      European context, fentanyls are 'low use but high risk/harm' substances. Evidence
      shows that Estonia stands out as having an endemic problem, while the use of
      fentanyls in other European countries appears to be geographically localised.
      Developments in illicit supply of fentanyls reflect the complexity of Europe's
      contemporary drug market: manifesting illicit production and use, the diversion
      and misuse of medicines, and the online sale of non-controlled new psychoactive
      substances. Likewise effective and integrated responses will need to address
      fentanyl production, diversion as well as ensuring the availability of harm
      reduction measures to users. 

PMID- 25976512
TI  - Granulocytes: Eosinophils enable the antitumour T cell response.

PMID- 25976514
TI  - T cell responses: B cells control T cell traffic.

PMID- 25976513
TI  - Fever and the thermal regulation of immunity: the immune system feels the heat.
AB  - Fever is a cardinal response to infection that has been conserved in warm-blooded
      and cold-blooded vertebrates for more than 600 million years of evolution. The
      fever response is executed by integrated physiological and neuronal circuitry and
      confers a survival benefit during infection. In this Review, we discuss our
      current understanding of how the inflammatory cues delivered by the thermal
      element of fever stimulate innate and adaptive immune responses. We further
      highlight the unexpected multiplicity of roles of the pyrogenic cytokine
      interleukin-6 (IL-6), both during fever induction and during the mobilization of
      lymphocytes to the lymphoid organs that are the staging ground for immune
      defence. We also discuss the emerging evidence suggesting that the adrenergic
      signalling pathways associated with thermogenesis shape immune cell function.

PMID- 25976516
TI  - Prism adaptation in Parkinson disease: comparing reaching to walking and freezers
      to non-freezers.
AB  - Visuomotor adaptation to gaze-shifting prism glasses requires recalibration of
      the relationship between sensory input and motor output. Healthy individuals
      flexibly adapt movement patterns to many external perturbations; however,
      individuals with cerebellar damage do not adapt movements to the same extent.
      People with Parkinson disease (PD) adapt normally, but exhibit reduced after
      effects, which are negative movement errors following the removal of the prism
      glasses and are indicative of true spatial realignment. Walking is particularly
      affected in PD, and many individuals experience freezing of gait (FOG), an
      episodic interruption in walking, that is thought to have a distinct
      pathophysiology. Here, we examined how individuals with PD with (PD + FOG) and
      without (PD - FOG) FOG, along with healthy older adults, adapted both reaching
      and walking patterns to prism glasses. Participants completed a visually guided
      reaching and walking task with and without rightward-shifting prism glasses. All
      groups adapted at similar rates during reaching and during walking. However,
      overall walking adaptation rates were slower compared to reaching rates. The PD -
      FOG group showed smaller after-effects, particularly during walking, compared to
      PD + FOG, independent of adaptation magnitude. While FOG did not appear to affect
      characteristics of prism adaptation, these results support the idea that the
      distinct neural processes governing visuomotor adaptation and storage are
      differentially affected by basal ganglia dysfunction in PD. 

PMID- 25976515
TI  - Immune modulation by bacterial outer membrane vesicles.
AB  - Gram-negative bacteria shed extracellular outer membrane vesicles (OMVs) during
      their normal growth both in vitro and in vivo. OMVs are spherical, bilayered
      membrane nanostructures that contain many components found within the parent
      bacterium. Until recently, OMVs were dismissed as a by-product of bacterial
      growth; however, findings within the past decade have revealed that both
      pathogenic and commensal bacteria can use OMVs to manipulate the host immune
      response. In this Review, we describe the mechanisms through which OMVs induce
      host pathology or immune tolerance, and we discuss the development of OMVs as
      innovative nanotechnologies.

PMID- 25976517
TI  - Subliminal perception of others' physical pain and pleasure.
AB  - Studies indicate that explicit and implicit processing of affectively charged
      stimuli may be reflected in specific behavioral markers and physiological
      signatures. This study investigated whether the pleasantness ratings of a neutral
      target were affected by subliminal perception of pleasant and painful facial
      expressions. Participants were presented images depicting face of non-famous
      models being slapped (painful condition), caressed (pleasant condition) or
      touched (neutral condition) by the right hand of another individual. In
      particular, we combined the continuous flash suppression technique with the
      affective misattribution procedure (AMP) to explore subliminal empathic
      processing. Measures of pupil reactivity along with empathy traits were also
      collected. Results showed that participants rated the neutral target as less or
      more likeable congruently with the painful or pleasant facial expression
      presented, respectively. Pupil dilation was associated both with the implicit
      attitudes (AMP score) and with empathic concern. Thus, the results provide
      behavioral and physiological evidence that state-related empathic reactivity can
      occur at an entirely subliminal level and that it is linked to autonomic
      responses and empathic traits. 

PMID- 25976519
TI  - Demographic, lifestyle, and health characteristics of older adults with
      prediabetes in England.
AB  - OBJECTIVE: To describe the demographic, lifestyle, and health characteristics of
      older adults with prediabetes compared to those with normal glucose levels or
      diabetes. METHOD: Participants were from the English Longitudinal Study of Aging
      2004-2005 (n=4168). Statistical analyses examined differences between people with
      prediabetes and 1) people with normal glucose levels and 2) people with diabetes.
      Design-based F-statistics and t-tests tested differences for each characteristic
      individually and multinomial logistic regression examined adjusted associations.
      Survey weighting and cluster information was used to generalize to the older
      English population. RESULTS: Compared to people with normal glucose levels,
      people with prediabetes were older (RR=1.05 95% CI 1.04-1.07), more likely to be
      employed (RR=1.27 95% CI 1.01-1.60), more likely to smoke (RR=2.21 95% CI 1.74
      2.80), and had higher BMIs (RR=1.08 95% CI 1.06-1.10). Compared to people with
      diabetes, people with prediabetes were more likely to be women (RR=2.12 95% CI
      1.57-2.86), more likely to be employed (RR=1.54 95% CI 1.02-2.33), had lower BMIs
      (RR=0.95 95% CI 0.93-0.98), were less likely to have a cardiovascular condition
      (RR=0.34 95% CI 0.24-0.47), and had higher self-rated health (chi(2)=26.08,
      p<0.001). CONCLUSION: Older adults with prediabetes have a unique set of
      characteristics that may inform prevention or intervention schemes.

PMID- 25976520
TI  - Spatial distribution of fishes in a Northwest Atlantic ecosystem in relation to
      risk of predation by a marine mammal.
AB  - 1. Numerous studies have shown that, at spatial scales of metres to several
      kilometres, animals balance the trade-off between foraging success and predation
      mortality by increasing their use of safer but less profitable habitats as
      predation risk increases. However, it is less clear whether prey respond
      similarly at the larger spatiotemporal scales of many ecosystems. 2. We determine
      whether this behaviour is evident in a large marine ecosystem, the southern Gulf
      of St. Lawrence (sGSL, 75 000 km(2) ) over a 42-year period. This ecosystem is
      characterized by a recent increase in the abundance of a large marine predator,
      the grey seal (Halichoerus grypus Fabricius), by more than an order of magnitude.
      3. We compared changes in spatial distribution over the 1971-2012 period between
      important prey of grey seals (Atlantic cod, Gadus morhua L.; white hake,
      Urophycis tenuis Mitchill; and thorny skate, Amblyraja radiata Donovan) and non
      prey fishes. 4. Distribution was modelled using generalized additive models
      incorporating spatially variable effects of predation risk, density dependence
      and water temperature. Distributions of cod, hake and skate were strongly related
      to risk of predation by seals, with distribution shifting into lower risk areas
      as predation risk increased. Non-prey species did not show similar changes in
      habitat use. Spatial variation in fish condition suggests that these low-risk
      areas are also less profitable for cod and skate in terms of food availability.
      The effects of density dependence and water temperature were also important in
      models, but did not account for the changes in habitat use as the risk of
      predation increased. 5. These results indicate that these fish are able to assess
      and respond to spatial variation in predation risk at very large spatial scales.
      They also suggest that non-consumptive 'risk' effects may be an important
      component of the declines in productivity of seal prey in this ecosystem, and of
      the indirect effects at lower trophic levels.

PMID- 25976518
TI  - Hindlimb movement modulates the activity of rostral fastigial nucleus neurons
      that process vestibular input.
AB  - Integration of vestibular and proprioceptive afferent information within the
      central nervous system is a critical component of postural regulation. We
      recently demonstrated that labyrinthine and hindlimb signals converge onto
      vestibular nucleus neurons, such that hindlimb movement modulates the activity of
      these cells. However, it is unclear whether similar convergence of hindlimb and
      vestibular signals also occurs upstream from the vestibular nuclei, particularly
      in the rostral fastigial nucleus (rFN). We tested the hypothesis that rFN neurons
      have similar responses to hindlimb movement as vestibular nucleus neurons.
      Recordings were obtained from 53 rFN neurons that responded to hindlimb movement
      in decerebrate cats. In contrast to vestibular nucleus neurons, which commonly
      encoded the direction of hindlimb movement (81 % of neurons), few rFN neurons (21
      %) that responded to leg movement encoded such information. Instead, most rFN
      neurons responded to both limb flexion and extension. Half of the rFN neurons
      whose activity was modulated by hindlimb movement received convergent vestibular
      inputs. These results show that rFN neurons receive somatosensory inputs from the
      hindlimb and that a subset of rFN neurons integrates vestibular and hindlimb
      signals. Such rFN neurons likely perform computations that participate in
      maintenance of balance during upright stance and movement. Although vestibular
      nucleus neurons are interconnected with the rFN, the dissimilarity of responses
      of neurons sensitive to hindlimb movement in the two regions suggests that they
      play different roles in coordinating postural responses during locomotion and
      other movements which entail changes in limb position. 

PMID- 25976521
TI  - The enhanced expression of IL-17-secreting T cells during the early progression
      of atherosclerosis in ApoE-deficient mice fed on a western-type diet.
AB  - Atherosclerosis is a chronic progressive inflammatory disorder and the leading
      cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell
      derived cytokines, such as inteferon (IFN)-gamma, interleukin (IL)-17 and IL-4,
      during the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-))
      mice, to understand the role of immune responses in different stages of
      atherosclerosis. Male ApoE(-/-) mice were fed a high-fat, western-type diet (WD:
      21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6
      wild-type control mice fed a standard chow diet. Atherosclerotic lesions appeared
      in the aortic sinus of ApoE(-/-) mice 4 weeks after WD and the lesions progressed
      and occupied >50% of the total sinus area 16 weeks after WD. Aortic IL-17 mRNA
      and protein expression started to increase in ApoE(-/-) mice after 4 weeks on the
      WD and peaked at around 8-12 weeks on the WD. In terms of systemic expression of
      T-cell-derived cytokines, IL-17 production from splenocytes after anti-CD3/CD28
      stimuli increased from 4 weeks on the WD, peaked at 12 weeks and returned to
      control levels at 16 weeks. The production of IFN-gamma and IL-4 (Th1 and Th2
      cytokines, respectively) from splenocytes was delayed compared with IL-17. Taken
      together, the present data indicate that Th17 cell response may be involved at an
      early stage in the development of atherosclerosis. 

PMID- 25976522
TI  - NF-kappaB upregulates ubiquitin C-terminal hydrolase 1 in diseased podocytes in
      glomerulonephritis.
AB  - Podocyte injury is a pivotal factor during the progression of glomerular
      diseases. It has been demonstrated that the expression of ubiquitin carboxy
      terminal hydrolase L1 (UCH-L1) is increased in injured podocytes in a number of
      types of glomerulonephritis. However, its mechanism of regulation remains to be
      elucidated. A previous study by our group suggested that UCH-L1 is a downstream
      protein of nuclear factor (NF)-kappaB signaling. In the present study, the
      involvement of NF-kappaB in the regulation of the expression of UCH-L1 was
      investigated in diseased podocytes in vivo and in vitro. Increases in the
      expression of phosphorylated NF-kappaB at p65 and UCH-L1 were detected using
      immunohistochemical analysis of kidney biopsy tissues from 56 cases of nephritis,
      including immunoglobulin A nephropathy, membranous glomerulonephritis and lupus
      nephritis. The two indicators were also analyzed using western blot analysis in
      cultured murine podocytes stimulated by inflammatory factors. The results of the
      present study demonstrated that in human renal biopsies of several cases of
      immune complex-mediated glomerulonephritis, the increases of NF-kappaB and UCH-L1
      were positively correlated with the number of diseased podocytes. By contrast, in
      non-immune complex-mediated glomerulonephritis, no clear activation of NF-kappaB
      and increase of UCH-L1 expression was observed. In vitro, immune stimulation also
      led to the upregulation of UCH-L1 through the NF-kappaB signaling pathway in
      mouse podocytes. In conclusion, the results of the present study suggested that
      the activation of NF-kappaB and upregulation of UCH-L1 in podocytes may be vital
      in podocyte injury associated with immune complex-mediated glomerulonephritis.

PMID- 25976523
TI  - Laura Piddock: Fights antibiotic resistance.

PMID- 25976524
TI  - A fluid response: Alpha-amylase reactions to acute laboratory stress are related
      to sample timing and saliva flow rate.
AB  - Salivary alpha-amylase (sAA) is used as a sympathetic (SNS) stress marker, though
      its release is likely co-determined by SNS and parasympathetic (PNS) activation.
      The SNS and PNS show asynchronous changes during acute stressors, and sAA
      responses may thus vary with sample timing. Thirty-four participants underwent an
      eight-minute memory task (MT) and cold pressor task (CPT). Cardiovascular SNS
      (pre-ejection period, blood pressure) and PNS (heart rate variability) activity
      were monitored continuously. Unstimulated saliva was collected repeatedly during
      and after each laboratory stressor, and sAA concentration (U/ml) and secretion
      (U/minute) determined. Both stressors increased anxiety. The MT caused an
      immediate and continued cardiac SNS activation, but sAA concentration increased
      at task cessation only (+54%); i.e., when there was SNS-PNS co-activation. During
      the MT sAA secretion even decreased (-35%) in conjunction with flow rate and
      vagal tone. The CPT robustly increased blood pressure but not sAA. In summary,
      sAA fluctuations did not parallel changes in cardiac SNS activity or anxiety. sAA
      responses seem contingent on sample timing and flow rate, likely involving both
      SNS and PNS influences. Verification using other stressors and contexts seems
      warranted. 

PMID- 25976525
TI  - The Timing of Infant Food Introduction in Families With a History of Atopy.
AB  - OBJECTIVE: To describe the timing of introduction and type of food introduced to
      infants with a family history of atopy. METHODS: We conducted a secondary
      analysis of foods introduced each month to an interventional birth cohort of 149
      infants at risk for atopy. RESULTS: Seven percent of infants received solid food
      prior to 4 months of age; 13% after 6 months of age. Hyperallergenic foods were
      introduced on average in the following order: wheat (8.7 months); eggs (11.2
      months); soy (13.0 months); fish (13.4 months); peanut (20.2 months); tree nuts
      (21.8 months); and other seafood (21.8 months). Asian race (odds ratio 3.94; 95%
      CI 1.14-13.58) and maternal history of food allergy (odds ratio 3.86; 95% CI 1.29
      11.56) were associated with late food introduction. CONCLUSION: Variation in
      timing of food introduction may reflect cultural preferences and/or previous
      experience with food allergy, as well as the ambiguous state of current
      recommendations.

PMID- 25976526
TI  - The Developmental Relationship Between Depressive Symptoms in Adolescence and
      Harmful Drinking in Emerging Adulthood: The Role of Peers and Parents.
AB  - Depressive symptoms have been linked to the development of harmful drinking in
      adolescence but it remains unclear to what extent this effect continues into
      emerging adulthood. Deviant peers represent a risk factor while parental
      monitoring is a protective factor for harmful drinking. The study explored the
      relationship between depressive symptoms and harmful drinking between early
      adolescence and emerging adulthood. We also assessed to what extent this
      relationship is mediated by the influence of deviant peers and whether parental
      monitoring weakens this process. The sample consisted of 2964 adolescents (64 %
      females) from the Avon Longitudinal Study of Parents and Children study assessed
      between the ages of 14 and 19. Using structural equation modelling, we found that
      affiliation with deviant peers mediated the association between depressive
      symptoms and harmful drinking after adjustment for socio-demographic variables,
      parental drinking and depression, teenager's sex, conduct problems as well as
      drinking and depressive symptoms in early adolescence. We also found that
      parental control and solicitation reduced the influence of deviant peers on
      harmful drinking. The results indicate that prevention programs should offer
      adolescents training for peer resistance training and monitoring skills training
      for parents may have a long-term effect at weakening peer influences on harmful
      drinking. 

PMID- 25976527
TI  - Religiousness and Levels of Hazardous Alcohol Use: A Latent Profile Analysis.
AB  - Prior person-centered research has consistently identified a subgroup of highly
      religious participants that uses significantly less alcohol when compared to the
      other subgroups. The construct of religious motivation is absent from existing
      examinations of the nuanced combinations of religiousness dimensions within
      persons, and alcohol expectancy valuations have yet to be included as outcome
      variables. Variable-centered approaches have found religious motivation and
      alcohol expectancy valuations to play a protective role against individuals'
      hazardous alcohol use. The current study examined latent religiousness profiles
      and hazardous alcohol use in a large, multisite sample of ethnically diverse
      college students. The sample consisted of 7412 college students aged 18-25 (M age
      = 19.77, SD age = 1.61; 75% female; 61% European American). Three latent profiles
      were derived from measures of religious involvement, salience, and religious
      motivations: Quest-Intrinsic Religiousness (highest levels of salience,
      involvement, and quest and intrinsic motivations; lowest level of extrinsic
      motivation), Moderate Religiousness (intermediate levels of salience,
      involvement, and motivations) and Extrinsic Religiousness (lowest levels of
      salience, involvement, and quest and intrinsic motivations; highest level of
      extrinsic motivation). The Quest-Intrinsic Religiousness profile scored
      significantly lower on hazardous alcohol use, positive expectancy outcomes,
      positive expectancy valuations, and negative expectancy valuations, and
      significantly higher on negative expectancy outcomes, compared to the other two
      profiles. The Extrinsic and Moderate Religiousness profiles did not differ
      significantly on positive expectancy outcomes, negative expectancy outcomes,
      negative expectancy valuations, or hazardous alcohol use. The results advance
      existing research by demonstrating that the protective influence of religiousness
      on college students' hazardous alcohol use may involve high levels on both quest
      and intrinsic religious motivation.

PMID- 25976529
TI  - A world of innovative ideas.
AB  - Nurse Researcher was proud to be the media partner for the RCN International
      Nursing Research Conference held in Nottingham last month. I was able to attend
      the conference and hear some of the innovative and creative work being undertaken
      by nurse researchers globally and found it motivating to meet so many
      enthusiastic nurse researchers. 

PMID- 25976528
TI  - Demethylmenaquinol is a substrate of Escherichia coli nitrate reductase A
      (NarGHI) and forms a stable semiquinone intermediate at the NarGHI quinol
      oxidation site.
AB  - Quinones are essential building blocks of respiration, a universal process
      dedicated to efficient harvesting of environmental energy and its conversion into
      a transmembrane chemiosmotic potential. Quinones differentiate mostly by their
      midpoint redox potential. As such, gamma-proteobacteria such as Escherichia coli
      are characterized by the presence of demethylmenaquinone (DMK) with an
      intermediate redox potential between low-potential (menaquinone) and high
      potential (ubiquinone) quinones. In this study, we show that demethylmenaquinol
      (DMKH2) is a good substrate for nitrate reductase A (NarGHI) in nitrate
      respiration in E. coli. Kinetic studies performed with quinol analogs on NarGHI
      show that removal of the methyl group on the naphthoquinol ring impacts modestly
      the catalytic constant but not the KM. EPR-monitored redox titrations of NarGHI
      enriched membrane vesicles reveal that endogeneous demethylmenasemiquinone (DMSK)
      intermediates are stabilized in the enzyme. The measured midpoint potential of
      the DMK/DMKH2 redox couple in NarGHI (E'm,7.5 (DMK/DMKH2) ~-70mV) is
      significantly lower than that previously measured for unbound species. High
      resolution pulsed EPR experiments demonstrate that DMSK are formed within the
      NarGHI quinol oxidation site. Overall, our results provide the first
      characterization of a protein-bound DMSK and allows for comparison for distinct
      use of three quinones at a single Q-site in NarGHI. 

PMID- 25976530
TI  - Issues in data analysis.
AB  - NURSE RESEARCHER publishes a wide range of methodology papers, many of which aim
      to give guidance to early researchers. Here I comment on two papers. The first,
      Qualitative case study data analysis: an example from practice ( Houghton et al
      2015 ) is clearly comprehendible by novice researchers. The second, Multiple
      imputation method for handling missing data: A case study of a secondary data
      analysis study ( Walani and Cleland 2015 ) is a rather different case. This is a
      useful paper but deals with a complex issue in quantitative data analysis. If you
      have looked at this paper and found it hard going then please read the following
      few paragraphs where I try to put this paper into context. 

PMID- 25976531
TI  - Qualitative case study data analysis: an example from practice.
AB  - AIM: To illustrate an approach to data analysis in qualitative case study
      methodology. BACKGROUND: There is often little detail in case study research
      about how data were analysed. However, it is important that comprehensive
      analysis procedures are used because there are often large sets of data from
      multiple sources of evidence. Furthermore, the ability to describe in detail how
      the analysis was conducted ensures rigour in reporting qualitative research. DATA
      SOURCES: The research example used is a multiple case study that explored the
      role of the clinical skills laboratory in preparing students for the real world
      of practice. Data analysis was conducted using a framework guided by the four
      stages of analysis outlined by Morse ( 1994 ): comprehending, synthesising,
      theorising and recontextualising. The specific strategies for analysis in these
      stages centred on the work of Miles and Huberman ( 1994 ), which has been
      successfully used in case study research. The data were managed using NVivo
      software. REVIEW METHODS: Literature examining qualitative data analysis was
      reviewed and strategies illustrated by the case study example provided.
      Discussion Each stage of the analysis framework is described with illustration
      from the research example for the purpose of highlighting the benefits of a
      systematic approach to handling large data sets from multiple sources.
      CONCLUSION: By providing an example of how each stage of the analysis was
      conducted, it is hoped that researchers will be able to consider the benefits of
      such an approach to their own case study analysis. IMPLICATIONS FOR
      RESEARCH/PRACTICE: This paper illustrates specific strategies that can be
      employed when conducting data analysis in case study research and other
      qualitative research designs.

PMID- 25976532
TI  - The multiple imputation method: a case study involving secondary data analysis.
AB  - AIM: To illustrate with the example of a secondary data analysis study the use of
      the multiple imputation method to replace missing data. BACKGROUND: Most large
      public datasets have missing data, which need to be handled by researchers
      conducting secondary data analysis studies. Multiple imputation is a technique
      widely used to replace missing values while preserving the sample size and
      sampling variability of the data. DATA SOURCE: The 2004 National Sample Survey of
      Registered Nurses. REVIEW METHODS: The authors created a model to impute missing
      values using the chained equation method. They used imputation diagnostics
      procedures and conducted regression analysis of imputed data to determine the
      differences between the log hourly wages of internationally educated and US
      educated registered nurses. DISCUSSION: The authors used multiple imputation
      procedures to replace missing values in a large dataset with 29,059 observations.
      Five multiple imputed datasets were created. Imputation diagnostics using time
      series and density plots showed that imputation was successful. The authors also
      present an example of the use of multiple imputed datasets to conduct regression
      analysis to answer a substantive research question. CONCLUSION: Multiple
      imputation is a powerful technique for imputing missing values in large datasets
      while preserving the sample size and variance of the data. Even though the
      chained equation method involves complex statistical computations, recent
      innovations in software and computation have made it possible for researchers to
      conduct this technique on large datasets. IMPLICATIONS FOR RESEARCH/PRACTICE: The
      authors recommend nurse researchers use multiple imputation methods for handling
      missing data to improve the statistical power and external validity of their
      studies.

PMID- 25976533
TI  - Levels of reduction in van Manen's phenomenological hermeneutic method: an
      empirical example.
AB  - AIM: To describe reduction as a method using van Manen's phenomenological
      hermeneutic research approach. BACKGROUND: Reduction involves several levels that
      can be distinguished for their methodological usefulness. Researchers can use
      reduction in different ways and dimensions for their methodological needs. DATA
      SOURCES: A study of Finnish multiple-birth families in which open interviews
      (n=38) were conducted with public health nurses, family care workers and parents
      of twins. REVIEW METHODS: A systematic literature and knowledge review showed
      there were no articles on multiple-birth families that used van Manen's method.
      Discussion The phenomena of the 'lifeworlds' of multiple-birth families consist
      of three core essential themes as told by parents: 'a state of constant
      vigilance', 'ensuring that they can continue to cope' and 'opportunities to share
      with other people'. CONCLUSION: Reduction provides the opportunity to carry out
      in-depth phenomenological hermeneutic research and understand people's lives. It
      helps to keep research stages separate but also enables a consolidated view.
      Social care and healthcare professionals have to hear parents' voices better to
      comprehensively understand their situation; they need further tools and training
      to be able to empower parents of twins. IMPLICATIONS FOR RESEARCH/PRACTICE: This
      paper adds an empirical example to the discussion of phenomenology, hermeneutic
      study and reduction as a method. It opens up reduction for researchers to
      exploit.

PMID- 25976534
TI  - Using unstructured diaries for primary data collection.
AB  - AIM: To give a reflective account of using unstructured handwritten diaries as a
      method of collecting qualitative data. BACKGROUND: Diaries are primarily used in
      research as a method of collecting qualitative data. There are some challenges
      associated with their use, including compliance rates. However, they can provide
      a rich source of meaningful data and can avoid the difficulties of participants
      trying to precisely recall events after some time has elapsed. DATA SOURCES: The
      author used unstructured handwritten diaries as her primary method of collecting
      data during her grounded theory doctoral study, when she examined the
      professional socialisation of nursing students. Over two years, 26 participants
      selected from four consecutive recruited groups of nursing students volunteered
      to take part in the study and were asked to keep a daily diary throughout their
      first five weeks of clinical experience. REVIEW METHODS: When using open-ended
      research questions, grounded theory's pragmatic approach permits the examination
      of processes thereby creating conceptual interpretive understanding of data.
      DISCUSSION: A wealth of rich, detailed data was obtained from the diaries that
      permitted the development of new theories regarding the effects early clinical
      experiences have on nursing students' professional socialisation. CONCLUSION:
      Diaries were found to provide insightful in-depth qualitative data in a resource
      friendly manner. IMPLICATIONS FOR RESEARCH/PRACTICE: Nurse researchers should
      consider using diaries as an alternative to more commonly used approaches to
      collecting qualitative data.

PMID- 25976535
TI  - Perils and pitfalls for clinicians embarking on qualitative research in
      physiotherapy.
AB  - AIM: To consider the pros and cons of focus groups versus interviews for studies
      interested in examining patient experiences of clinical interventions. The paper
      looks at the hazards of being a clinician when collecting qualitative data and
      shares these experiences to provide useful learning for other clinicians
      embarking on qualitative approaches. BACKGROUND: Sub-acromial decompression
      surgery (SAD) is the accepted, surgical intervention for shoulder impingement
      syndrome. Evidence suggests that outcomes from SAD are no more superior to
      conservative management. This raises questions as to whether alternative
      explanations such as patient experience are at play when considering patient
      outcomes. DATA SOURCES: A study looking at patients' experiences of subacromial
      decompression surgery six months after the operation. REVIEW METHODS: One small
      focus group and one individual interview took place to explore patient experience
      following sub-acromial decompression shoulder surgery. DISCUSSION: Focus groups
      risk producing competitive and comparative discussions, and clinical researchers
      require sufficient training and mentoring to recognise and assist group dynamics.
      The study exposed ways in which clinicians involved in collecting data may be
      injured to aspects of patients' experiences, and accordingly may not explore in
      depth aspects important to patients. CONCLUSION: This paper highlights the
      importance of novice researchers thinking carefully about the capacity for
      'practitioner eyes' to influence analytical decisions about study design and the
      direction of data collection. Focus group interactions are complex and risk being
      underestimated by inexperienced clinical researchers. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Novice researchers are advised to be open to the possibility
      that unpredictable situations are likely to occur and expose assumptions about
      the study design. Preparation and guidance is required to avoid some of the
      challenges and manage group dynamics effectively in the first instance.

PMID- 25976536
TI  - Transforming the findings of narrative research into poetry.
AB  - AIM: To offer dramatic poetry as representing findings from narrative research
      that is more accessible. BACKGROUND: This article is drawn from the author's
      doctorate work on how students' stories about their 'clinical' experiences can
      aid learning. DATA SOURCES: Nursing students' stories of clinical practice
      experiences when engaged in the care of patients represented as dramatic poetry.
      REVIEW METHODS: Qualitative analytical approaches in narrative data analysis to
      provide a review of student stories from a variety of perspectives. DISCUSSION:
      This article illustrates a method for converting story data to poetry. It
      suggests that a range of audiences can learn from nursing students' stories of
      clinical practice when translated into dramatic poetry. CONCLUSION: Audiences can
      come close to understanding what students are experiencing in practice when
      engaged in the care of patients and learning from their practice experiences,
      when these experiences are expressed as dramatic poetry. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Representing findings from narrative research as dramatic
      poetry can help audiences engage with nursing students' experiences at an
      emotional level. Enabling researchers and readers to become immersed in the poem
      transforming their understanding of what the students have learned.

PMID- 25976537
TI  - Research must be relevant to real life.
AB  - JANE MILLS is Professor of Nursing at James Cook University, Australia and the
      director of its Centre for Nursing and Midwifery Research. She is an
      internationally recognised grounded theorist and has significant expertise in
      rural nursing. 

PMID- 25976540
TI  - Identification of G protein coupled receptors for opsines and neurohormones in
      Rhodnius prolixus. Genomic and transcriptomic analysis.
AB  - The importance of Chagas disease motivated the scientific effort to obtain the
      complete genomic sequence of the vector species Rhodnius prolixus, this
      information is also relevant to the understanding of triatomine biology in
      general. The central nervous system is the key regulator of insect physiology and
      behavior. Neurohormones (neuropeptides and biogenic amines) are the chemical
      messengers involved in the regulation and integration of neuroendocrine signals.
      In insects, this signaling is mainly mediated by the interaction of neurohormone
      ligands with G protein coupled receptors (GPCRs). The recently sequenced R.
      prolixus genome provides us with the opportunity to analyze this important family
      of genes in triatomines, supplying relevant information for further functional
      studies. Next-generation sequencing methods offer an excellent opportunity for
      transcriptomic exploration in key organs and tissues in the presence of a
      reference genome as well as when a reference genome is not available. We
      undertook a genomic analysis to obtain a genome-wide inventory of opsines and the
      GPCRs for neurohormones in R. prolixus. Furthermore, we performed a
      transcriptomic analysis of R. prolixus central nervous system, focusing on
      neuropeptide precursor genes and neurohormone and opsines GPCRs. In addition, we
      mined the whole transcriptomes of Triatoma dimidiata, Triatoma infestans and
      Triatoma pallidipennis - three sanitary relevant triatomine species - to identify
      neuropeptide precursors and GPCRs genes. Our study reveals a high degree of
      sequence conservation in the molecular components of the neuroendocrine system of
      triatomines. 

PMID- 25976541
TI  - Geographic spread, genetics and functional characteristics of ryanodine receptor
      based target-site resistance to diamide insecticides in diamondback moth,
      Plutella xylostella.
AB  - Anthranilic diamides and flubendiamide belong to a new chemical class of
      insecticides acting as conformation sensitive activators of the insect ryanodine
      receptor (RyR). These compounds control a diverse range of different herbivorous
      insects including diamondback moth, Plutella xylostella (Lepidoptera:
      Plutellidae), a notorious global pest on cruciferous crops, which recently
      developed resistance due to target-site mutations located in the trans-membrane
      domain of the Plutella RyR. In the present study we further investigated the
      genetics and functional implications of a RyR G4946E target-site mutation we
      recently identified in a Philippine diamondback moth strain (Sudlon). Strain
      Sudlon is homozygous for the G4946E mutation and has been maintained under
      laboratory conditions without selection pressure for almost four years, and still
      exhibit stable resistance ratios of >2000-fold to all commercial diamides. Its F1
      progeny resulting from reciprocal crosses with a susceptible strain (BCS-S)
      revealed no maternal effects and a diamide susceptible phenotype, suggesting an
      autosomally almost recessive mode of inheritance. Subsequent back-crosses
      indicate a near monogenic nature of the diamide resistance in strain Sudlon.
      Radioligand binding studies with Plutella thoracic microsomal membrane
      preparations provided direct evidence for the dramatic functional implications of
      the RyR G4946E mutation on both diamide specific binding and its concentration
      dependent modulation of [(3)H]ryanodine binding. Computational modelling based on
      a cryo-EM structure of rabbit RyR1 suggests that Plutella G4946E is located in
      trans-membrane helix S4 close to S4-S5 linker domain supposed to be involved in
      the modulation of the voltage sensor, and another recently described mutation,
      I4790M in helix S2 approx. 13 A opposite of G4946E. Genotyping by pyrosequencing
      revealed the presence of the RyR G4946E mutation in larvae collected in 2013/14
      in regions of ten different countries where diamide insecticides largely failed
      to control diamondback moth populations. Thus, our study highlights the global
      importance of the G4946E RyR target-site mutation, which as a mechanism on its
      own, confers high-level resistance to diamide insecticides in diamondback moth.

PMID- 25976542
TI  - Another potential carp killer?: Carp Edema Virus disease in Germany.
AB  - BACKGROUND: Infections with carp edema virus, a pox virus, are known from
      Japanese koi populations since 1974. A characteristic clinical sign associated
      with this infection is lethargy and therefore the disease is called "koi sleepy
      disease". Diseased koi also show swollen gills, enophthalmus, and skin lesions.
      Mortality rates up to 80 % are described. For a long period of time, disease
      outbreaks seemed to be restricted to Japan. However, during the last years
      clinical outbreaks of koi sleepy disease also occurred in the UK and in the
      Netherlands. CASE PRESENTATION: In spring 2014 koi from different ponds showing
      lethargic behavior, skin ulcers, inflammation of the anus, enophthalmus, and gill
      necrosis were presented to the laboratory for diagnosis. In all cases, new koi
      had been purchased earlier that spring from the same retailer and introduced into
      existing populations. Eleven koi from six ponds were examined for ectoparasites
      and for bacterial and viral infections (cyprinid herpesviruses in general and
      especially koi herpesvirus (KHV) known formally as Cyprinid herpesvirus 3 (CyHV
      3); and Carp Edema Virus). In most of the cases parasites were not detected from
      skin and gills. Only opportunistic freshwater bacteria were isolated from skin
      ulcers. In cell cultures no cytopathic effect was observed, and none of the
      samples gave positive results in PCR tests for cyprinid herpesviruses. By
      analyzing gill tissues for CEV in seven out of eleven samples by a nested PCR,
      PCR products of 547 bp and 180 bp (by using nested primers) could be amplified.
      An outbreak of Koi Sleepy Disease was confirmed by sequencing of the PCR
      products. These results confirm the presence of CEV in German koi populations.
      CONCLUSION: A clinical outbreak of "koi sleepy disease" due to an infection with
      Carp Edema Virus was confirmed for the first time in Germany. To avoid
      transmission of CEV to common carp testing of CEV should become part of fish
      disease surveillance programs.

PMID- 25976543
TI  - Burden of invasive pneumococcal disease (IPD) in Sri-Lanka: Deriving a reasonable
      measure for vaccine introduction decision making.
AB  - PURPOSE: The lack of evidence on the disease burden has been an obstacle for
      decision-making on introducing pneumococcal vaccines in Sri-Lanka. Hence, the
      purpose of this study is to determine the incidence of invasive pneumococcal
      disease among children under five-years of age in Sri-Lanka's Colombo district.
      METHODS: In a community-based study, using a sample of 2310 children, we
      identified syndromes associated with pneumococcal disease (pneumonia, meningitis,
      sepsis). The estimates of annual cumulative incidence of invasive pneumococcal
      disease were derived by having applied proportions of laboratory confirmed
      invasive pneumococcal disease among all-cause syndromes associated with
      pneumococcal infection obtained from the hospital-based invasive bacterial
      disease sentinel surveillance and findings of the community-based study to
      population parameters of the district. The estimates of invasive pneumococcal
      pneumonia and sepsis based on low-sensitive, culture confirmation were adjusted
      by a correction factor. RESULTS: The annual cumulative incidence of all-cause
      clinical syndromes associated with pneumococcal disease (pneumonia, meningitis,
      sepsis) were 1.3, 0.52, 0.39 per 100 children, respectively. The estimate of
      adjusted, invasive pneumococcal disease cumulative incidence was 206.3 per
      100,000 while estimates of pneumococcal pneumonia, meningitis and sepsis
      cumulative incidence were 147.9, 13.2 and 45.2 per 100,000 under-five children.
      CONCLUSION: Reasonable estimates of invasive pneumococcal disease could be
      derived by using incidence of clinical syndromes associated with pneumococcal
      disease obtained from population-based studies and proportion of pneumococcal
      infection among all-cause clinical syndromes associated with pneumococcal disease
      generated from hospital-based sentinel surveillance. These estimates may help
      informed decision-making on introduction of pneumococcal conjugated vaccine.

PMID- 25976544
TI  - High-throughput data analysis and data integration for vaccine trials.
AB  - Rational vaccine development can benefit from biomarker studies, which help to
      predict, optimize and evaluate the immunogenicity of vaccines and ultimately
      provide surrogate endpoints for vaccine trials. Systems biology approaches
      facilitate acquisition of both simple biomarkers and complex biosignatures. Yet,
      evaluation of high-throughput (HT) data requires a plethora of tools for data
      integration and analysis. In this review, we present an overview of methods for
      evaluation and integration of large amounts of data collected in vaccine trials
      from similar and divergent molecular HT techniques, such as transcriptomic,
      proteomic and metabolic profiling. We will describe a selection of relevant
      statistical and bioinformatic approaches that are frequently associated with
      systems biology. We will present data dimension reduction techniques, functional
      analysis approaches and methods of integrating heterogeneous HT data. Finally, we
      will provide a few examples of applications of these techniques in vaccine
      research and development. 

PMID- 25976547
TI  - A novel nucleoside from the edible mushroom, Tricholoma japonicum.
AB  - A novel nucleoside, 9-beta-D-ribopyranosylpurine (2), along with three known
      nucleosides, adenosine (1), uridine (3) and nebularine (4), were isolated from
      the edible mushroom, Tricholoma japonicum. The structure of 2 was determined as 9
      beta-D-ribopyranosylpurine by comparing the reported spectral data of 2 with that
      of a synthetic compound. Isolation of the glycoside, which contains the sugar
      ribopyranose, from natural resources is very unusual. There are reports on the
      synthesis of 9-beta-D-ribopyranosylpurine (2), but this is the first report on
      the isolation from natural resources. The antiproliferative activity of compounds
      1-4 was evaluated using human umbilical vein endothelial cells. Compound 4 showed
      the highest inhibitory activity. 

PMID- 25976545
TI  - Development of a candidate influenza vaccine based on virus-like particles
      displaying influenza M2e peptide into the immunodominant region of hepatitis B
      core antigen: Broad protective efficacy of particles carrying four copies of M2e.
AB  - A long-term objective when designing influenza vaccines is to create one with
      broad cross-reactivity that will provide effective control over influenza, no
      matter which strain has caused the disease. Here we summarize the results from an
      investigation into the immunogenic and protective capacities inherent in
      variations of a recombinant protein, HBc/4M2e. This protein contains four copies
      of the ectodomain from the influenza virus protein M2 (M2e) fused within the
      immunodominant loop of the hepatitis B virus core antigen (HBc). Variations of
      this basic design include preparations containing M2e from the consensus human
      influenza virus; the M2e from the highly pathogenic avian A/H5N1 virus and a
      combination of two copies from human and two copies from avian influenza viruses.
      Intramuscular delivery in mice with preparations containing four identical copies
      of M2e induced high IgG titers in blood sera and bronchoalveolar lavages. It also
      provoked the formation of memory T-cells and antibodies were retained in the
      blood sera for a significant period of time post immunization. Furthermore, these
      preparations prevented the death of 75-100% of animals, which were challenged
      with lethal doses of virus. This resulted in a 1.2-3.5 log10 decrease in viral
      replication within the lungs. Moreover, HBc particles carrying only "human" or
      "avian" M2e displayed cross-reactivity in relation to human (A/H1N1, A/H2N2 and
      A/H3N2) or A/H5N1 and A(H1N1)pdm09 viruses, respectively; however, with the
      particles carrying both "human" and "avian" M2e this effect was much weaker,
      especially in relation to influenza virus A/H5N1. It is apparent from this work
      that to quickly produce vaccine for a pandemic it would be necessary to have
      several variations of a recombinant protein, containing four copies of M2e (each
      one against a group of likely influenza virus strains) with these relevant
      constructs housed within a comprehensive collection Escherichia coli-producers
      and maintained ready for use. 

PMID- 25976548
TI  - Examining the Critical Roles of Protons in Facilitating Oxidation of Chloride
      Ions by Permanganates: A Cluster Model Study.
AB  - The oxidation power of permanganates (MnO4(-)) is known to be strongly dependent
      on pH values, and is greatly enhanced in acidic solutions, in which, for example,
      MnO4(-) can even oxidize Cl(-) ions to produce Cl2 molecules. Although such
      dependence has been ascribed due to the different reduced states of Mn affordable
      in different pH media, a molecular level understanding and characterization of
      initial redox pair complexes available in different pH solutions is very limited.
      Herein, we report a comparative study of [MnO4](-) and [MnO4.Sol](-) (Sol = H2O,
      KCl, and HCl) anion clusters by negative ion photoelectron spectroscopy (NIPES)
      and theoretical computations to probe chemical bonding and electronic structures
      of [MnO4.Sol](-) clusters, aimed to obtain a microscopic understanding of how
      MnO4(-) interacts with surrounding molecules. Our study shows that H2O behaves as
      a solvent molecule, KCl is a spectator bound by pure electrostatic interactions,
      both of which do not influence the MnO4(-) identity in their respective clusters.
      In contrast, in [MnO4.HCl](-), the proton is found to interact with both MnO4(-)
      and Cl(-) with appreciable covalent characters, and the frontier MOs of the
      cluster are comprised of contributions from both MnO4(-) and Cl(-) moieties.
      Therefore, the proton serves as a chemical bridge, bringing two negatively
      charged redox species together to form an intimate redox pair. By adding more
      H(+) to MnO4(-), the oxygen atom can be taken away in the form of a water
      molecule, leaving MnO4(-) as an electron deficient MnO3(+) species, which can
      subsequently oxidize Cl(-) ions. 

PMID- 25976546
TI  - Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting
      System.
AB  - BACKGROUND: In October 2012, the Advisory Committee on Immunization Practices
      (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and
      acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's
      prior history of receiving Tdap. A retrospective cohort study to assess the
      safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD)
      sites during 2010-2012 found a small but statistically significant increased risk
      of chorioamnionitis. OBJECTIVE: We conducted a review of the VAERS database to
      describe reports of chorioamnionitis following receipt of any vaccines. METHODS:
      We searched the VAERS database for reports of chorioamnionitis after any vaccine
      in the United States during the period from July 1, 1990 through February 2,
      2014. RESULTS: VAERS received 31 reports of chorioamnionitis out of 3389
      pregnancy reports in 24 years. The three most common vaccines in these reports
      were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4),
      and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight
      percent of reports had at least one reported risk factor for chorioamnionitis.
      Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6
      stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term
      birth; maternal outcomes included two reports of postpartum hemorrhage and one
      report of maternal admission to the intensive care unit. No maternal deaths were
      reported. CONCLUSION: Chorioamnionitis was found to be uncommonly reported,
      representing 1% of pregnancy reports to VAERS. A majority of reports had at least
      one risk factor for chorioamnionitis.

PMID- 25976549
TI  - THO2, a core member of the THO/TREX complex, is required for microRNA production
      in Arabidopsis.
AB  - The THO/TREX complex mediates transport of nascent mRNAs from the nucleus towards
      the cytoplasm in animals, and has a role in small interfering RNA-dependent
      processes in plants. Here we describe five mutant alleles of Arabidopsis thaliana
      THO2, which encodes a core subunit of the plant THO/TREX complex. tho2 mutants
      present strong developmental defects resembling those in plants compromised in
      microRNA (miRNA) activity. In agreement, not only were the levels of siRNAs
      reduced in tho2 mutants, but also those of mature miRNAs. As a consequence, a
      feedback mechanism is triggered, increasing the amount of miRNA precursors, and
      finally causing accumulation of miRNA-targeted mRNAs. Yeast two-hybrid
      experiments and confocal microscopy showed that THO2 does not appear to interact
      with any of the known miRNA biogenesis components, but rather with the splicing
      machinery, implying an indirect role of THO2 in small RNA biogenesis. Using an
      RNA immunoprecipitation approach, we found that THO2 interacts with miRNA
      precursors, and that tho2 mutants fail to recruit such precursors into the miRNA
      processing complex, explaining the reduction in miRNA production in this mutant
      background. We also detected alterations in the splicing pattern of genes
      encoding serine/arginine-rich proteins in tho2 mutants, supporting a previously
      unappreciated role of the THO/TREX complex in alternative splicing. 

PMID- 25976550
TI  - European Progestin Club Guidelines for prevention and treatment of threatened or
      recurrent (habitual) miscarriage with progestogens.
AB  - This guideline has been developed based on studied and clinical investigations.
      Therefore, it appears to be appropriate to use all the available evidence, which
      are very encouraging, in a summarized form to propose guidelines by a group of
      European experts in order to give the gynecologists, obstetricians and
      reproductive medicine specialists have direction with regard to the prevention or
      treatment of miscarriage for the benefit of the endangered pregnancies. There are
      a number of statements, opinions and guidelines already published for this topic,
      which are not entirely in agreement. 

PMID- 25976551
TI  - Two Gonostomatid Ciliates from the Soil of Lombardia, Italy; including Note on
      the Soil Mapping Project.
AB  - Two gonostomatid ciliates, Gonostomum paronense n. sp. and G. strenuum, isolated
      from the soil sample of paddy field, Lombardia, Italy, were investigated using
      live observation and protargol impregnation. Gonostomum paronense n. sp. is
      mainly characterized by a tailed body, frontoventral cirri arranged in pairs, and
      presence of pretransverse and transverse cirri. Morphologically and
      morphometrically, the new species is similar to Gonostomum namibiense in having a
      tailed body and frontoventral cirral pairs; however, it differs mainly in the
      number of frontoventral cirral pairs (seven vs. three). Phylogenetic analyses
      based on the SSU rDNA sequences show that the new species is more closely related
      to G. namibiense than to G. strenuum, supporting the morphological classification
      based on the cirral pattern and the tailed body. However, due to the poor nodal
      support and absence of gene sequence of the type species Gonostomum, a more
      robust phylogeny of this group still remains unresolved. The biometric data of
      the Italian population of Gonostomum strenuum overlap with those from other known
      populations. Both species were collected from the industrial area of Parona, in
      the framework of the "Soil Mapping, Lombardia" project in which, for the first
      time in Italy, soil ciliates were used as bioindicators of soil quality. 

PMID- 25976552
TI  - Cationic albumin-conjugated chelating agent as a novel brain drug delivery system
      in neurodegeneration.
AB  - The critical role of metal ions and in particular iron in oxidative stress and
      protein aggregation offers chelation therapy as a sensible pharmaceutical
      strategy in oxidative stress-induced neuronal damages. In this research, we
      conjugated an iron-chelating agent, deferasirox, to cationized human serum
      albumin molecules in order to develop a novel brain delivery system for the
      management of neurodegenerative disorders due to the significant role of
      oxidative stress-induced neuronal injury in such diseases. Cationized albumin is
      known to be able to transport to brain tissue via adsorptive-mediated
      transcytosis. The developed structures were molecularly characterized, and their
      conjugation ratio was determined. PC12 cell line was utilized to evaluate the
      neuroprotective features of these newly developed molecules in the presence of
      hydrogen peroxide neuronal damage and to identify the mechanisms behind the
      observed neuronal protection including apoptotic and autophagic pathways.
      Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the
      impact of conjugated structures in vivo. Data analysis revealed that the
      conjugated species were able to hinder apoptotic cell death while enhancing
      autophagic process. The developed conjugated species were also able to attenuate
      amyloid beta-induced learning deficits when administered peripherally. 

PMID- 25976555
TI  - [Not Available].

PMID- 25976553
TI  - Intracellular calcium levels as screening tool for nanoparticle toxicity.
AB  - The use of engineered nano-sized materials led to revolutionary developments in
      many industrial applications and in the medical field. These materials, however,
      also may cause cytotoxicity. In addition to size, surface properties and shape
      were identified as relevant parameters for cell damage. Cell damage may occur as
      disruption of membrane integrity, induction of apoptosis and by organelle damage.
      Generation of oxidative stress may serve as an indicator for cytotoxicity.
      Effects occurring upon short contact of particles with cells, for instance in the
      systemic blood circulation, could be identified according to increases of
      intracellular [Ca(2+) ] levels, which are caused by variety of toxic stimuli.
      Negatively charged, neutral and positively charged polystyrene particles of
      different sizes were used to study the role of size and surface properties on
      viability, membrane disruption, apoptosis, lysosome function, intracellular
      [Ca(2+) ] levels and generation of oxidative stress. Silica particles served to
      test this hypothesis. Twenty nm polystyrene particles as well as 12 nm and 40 nm
      silica particles caused membrane damage and apoptosis with no preference of the
      surface charge. Only 20 nm plain and amine functionalized polystyrene particles
      cause oxidative stress and only the plain particles lysosomal damage. A potential
      role of surface charge was identified for 200 nm polystyrene particles, where
      only the amidine particles caused lysosomal damage. Increases in intracellular
      [Ca(2+) ] levels and cytotoxicity after 24 h was often linked but determination
      of intracellular [Ca(2+) ] levels could serve to characterize further the type of
      membrane damage.

PMID- 25976556
TI  - [Not Available].

PMID- 25976554
TI  - Determining the prevalence of SCCmec polymorphism, virulence and antibiotic
      resistance genes among methicillin-resistant Staphylococcus aureus (MRSA)
      isolates collected from selected hospitals in west of Iran.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important
      pathogens worldwide and compared to other staphylococcal species that are
      associated with higher mortality rate. A total of 500 Staphylococcus spp. was
      collected from selected hospitals in Ilam, Kermanshah, Khorram Abad and Hamadan
      cities and, via phenotypic and genotypic methods, was assessed to find MRSA. The
      presence or absence of prevalent antibiotic resistance genes and virulence genes
      was evaluated among MRSA isolates, using polymerase chain reaction (PCR) method,
      and then the SCCmec typing of these isolates was assayed by multiplex PCR. A
      total of 372 (74.4%) Stapylococcus spp. isolates were identified as S. aureus,
      among which 200 (53.8%) possessed the mecA gene and were distinguished as MRSA.
      All of MRSA isolates contained blaZ gene. The frequency of ermA and ermC genes
      among erythromycin-resistant MRSA isolates was 21.6% and 66.7%, respectively. The
      frequency of the virulence genes eta, hla and sea among MRSA isolates was 10%,
      80.5% and 100%, respectively. SCCmec type IV accounted for 30.6% of the MRSA
      isolates and SCCmec type III, SCCmec type II and SCCmec type I accounted for 30%,
      22% and 17.5% of the isolates, respectively. The antibiotic resistance genes and
      the virulence genes of blaZ, hla, sea, eta and ermC had high frequencies among
      the MRSA isolates. This study showed that the antibiotic resistance genes had
      higher frequencies among SCCmec types I and IV, which confirms the previous
      reports in this field. 

PMID- 25976557
TI  - Manual perineal support at the time of childbirth: a systematic review and meta
      analysis.
AB  - BACKGROUND: Genital tract trauma is common with vaginal births and is associated
      with significant morbidity, particularly with obstetric anal sphincter injuries
      (OASIS). Debate continues regarding the effectiveness of perineal support during
      childbirth in reducing the risk of trauma. OBJECTIVES: This review aimed to
      assess the effect of routine 'hands on'/manual perineal support (MPS) during
      childbirth, versus ad hoc/no perineal support ('hands off/poised'), on the risk
      and degree of perineal trauma. SEARCH STRATEGY: This review is registered on
      PROSPERO
      (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007058). We
      searched the CENTRAL, Embase, Medline, CINAHL, and OVIDs midwifery and infant
      care databases (from inception to December 2014). SELECTION CRITERIA: Published
      randomised controlled trials (RCTs) and non-randomised studies (NRSs) evaluating
      any 'hands on' perineal support technique during childbirth. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trials for inclusion, data
      extraction, and methodological quality. Discrepancies were resolved by discussion
      with a third reviewer. MAIN RESULTS: We included five RCTs and seven NRSs in the
      review. Meta-analysis of RCTs did not demonstrate a statistically significant
      protective effect of MPS on the risk of OASIS (three studies, 6647 women;
      relative risk, RR 1.03; 95% confidence interval, 95% CI 0.32-3.36; statistical
      test for heterogeneity I(2) = 71%). Meta-analysis of NRSs showed a significant
      reduction in the risk of OASIS with MPS (three studies, 74,744 women; RR 0.45;
      95% CI 0.40-0.50; I(2) = 32%). CONCLUSION: Current evidence is insufficient to
      drive change in practice. An adequately powered randomised trial with an
      efficient design to evaluate the complex interventions adopted as part of MPS
      policies, ensuring controlled childbirth, is urgently needed.

PMID- 25976558
TI  - Novel calicivirus from a ferret badger (Melogale moschata) in China.
AB  - We describe the isolation and complete genome sequence of a new calicivirus, FBCV
      JX12, isolated from a ferret badger (Melogale moschata). Comparison of FBCV-JX12
      with other vesiviruses revealed that it shared the highest amino acid sequence
      identities of 71.6, 60.5, and 59.3% in the nonstructural protein, VP1, and VP2,
      respectively, with MCV-DL2007 (mink calicivirus). Phylogenetic analysis of the
      whole genomic sequence showed that it clustered most closely with MCV-DL2007 of
      the genus Vesivirus, but with low nucleotide similarity in the three open reading
      frames (62.1-68.5%).

PMID- 25976559
TI  - [Hypoaesthesic erythematous plaques in patients from Brazil, a new case of
      leprosy imported].

PMID- 25976562
TI  - Hospital vision and mission strategic planning and departmental performance.

PMID- 25976560
TI  - Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in
      pancreatic islets.
AB  - The number of pro-alpha cells is known to increase in response to beta cell
      injury and these cells then generate glucagon-like peptide-1 (GLP-1), thus
      attenuating the development of diabetes. The aim of the present study was to
      further examine the role and the mechanisms responsible for intra-islet GLP-1
      production as a self-protective response against lipotoxicity. The levels of the
      key enzyme, prohormone convertase 1/3 (PC1/3), as well as the synthesis and
      release of GLP-1 in models of lipotoxicity were measured. Furthermore, islet
      viability, apoptosis, oxidative stress and inflammation, as well as islet
      structure were assessed after altering GLP-1 receptor signaling. Both prolonged
      exposure to palmitate and a high-fat diet facilitated PC1/3 expression, as well
      as the synthesis and release of GLP-1 induced by beta cell injury and the
      generation of pro-alpha cells. Prolonged exposure to palmitate increased reactive
      oxygen species (ROS) production, and the antioxidant, N-acetylcysteine (NAC),
      partially prevented the detrimental effects induced by palmitate on beta cells,
      resulting in decreased GLP-1 levels. Furthermore, the inhibition of GLP-1
      receptor (GLP-1R) signaling by treatment with exendin-(9-39) further decreased
      cell viability, increased cell apoptosis and caused a stronger inhibition of the
      beta cell-specific transcription factor, pancreatic duodenal homeobox 1 (PDX1).
      Moreover, treatment with the GLP-1R agonist, liraglutide, normalized islet
      structure and function, resulting in a decrease in cell death and in the
      amelioration of beta cell marker expression. Importantly, liraglutide maintained
      the oxidative balance and decreased inflammatory factor and p65 expression.
      Overall, our data demonstrate that an increase in the number of pro-alpha cells
      and the activation of the intra-islet GLP-1 system comprise a self-defense
      mechanism for enhancing beta cell survival to combat lipid overload, which is in
      part mediated by oxidative stress and inflammation.

PMID- 25976563
TI  - Haematological causes of thrombocytopenia in children at Aga Khan University
      Hospital, Karachi.
AB  - OBJECTIVE: To identify the haematological causes of thrombocytopenia in children
      admitted at a tertiary care hospital. METHODS: The prospective, descriptive study
      was carried out at the Aga Khan University Hospital, Karachi, from September 3,
      2009 to March 3, 2010, and comprised children between one month and 14 years of
      age with platelet count less than15000. After reviewing the record, a
      questionnaire was filled and data was analysed using SPSS 15. RESULTS: Out of 108
      patients in the study, 69(64%) were male and 39(36%) were female. The overall
      mean age was 69+/-46.54 months (range: 12-168 months). The mean platelet count
      was 59.8+/-46.1/ul (range: 1,000-149,000/ul). Besides, 24 (22.2%) children had
      mild thrombocytopenia, 34(31.5%) had moderate and 50(46.3 %) had severe
      thrombocytopenia. The causes of haematological thrombocytopenia in descending
      order of frequency was acute lymphoblastic leukaemia 17(15.7%), idiopathic
      thrombocytopenic purpura 10(8.3%) and aplastic anaemia 5(4.6%). CONCLUSIONS:
      Acute lymphoblastic leukaemia was the commonest cause of haematological
      thrombocytopenia followed by idiopathic thrombocytopenic purpura and aplastic
      anaemia.

PMID- 25976564
TI  - The antibacterial effect of four mouthwashes against streptococcus mutans and
      escherichia coli.
AB  - OBJECTIVE: To evaluate the antimicrobial properties of several mouthwash
      concentrations on oral Streptococcus mutans and Escherichia coli. METHODS: The
      study was conducted at Shiraz Medicine School in 2011. Serial dilutions of
      Chlorohexidin, Oral B and Persica and Irsha (2,4,8,16,64,128) were prepared in
      Muller-Hinton media. Minimum inhibitory concentration was visually determined and
      defined as the lowest concentration of each oral washing which inhibited > 95%
      growth reduction compared to the growth control well. RESULTS: Chlorhexidine,
      Oral B and Irsha mouthwash inhibited Streptococcus mutans even with diluted
      concentrations. Also, Chlorhexidine and Oral B prohibited Escherichia coli with
      different potencies. But Persica had no antimicrobial activity against either
      Escherichia coli or Streptococcus mutans. CONCLUSIONS: Chlorhexidine, Irsha, and
      Oral B mouthwashes can be used for antimicrobial effects, especially on
      Streptococcus mutans. This chemical activity of mouthwashes is an adjuvant for
      mechanical removing of plaque. However, the antimicrobial effect of
      Persicaremains controversial.

PMID- 25976565
TI  - Association between hepcidin, haemoglobin level and iron status in stage 4
      chronic kidney disease patients with anaemia.
AB  - OBJECTIVE: To explore the probable association of serum hepcidin and haemoglobin
      levels with iron and inflammation statuses in patients of chronic kidney disease
      stage 4 with anaemia. METHODS: The cross-sectional study was conducted at Tabriz
      University of Medical Sciences, Iran, from March 2011 to October 2012, and
      comprised patients of chronic kidney disease stage 4 with anaemia. Serum
      biochemical factors as well as hepcidin, ferritin, interleukin 6, high
      sensitivity C-reactive protein and iron levels were measured using standard
      methods. Statistical correlations were established using regression analysis and
      Pearson's correlation coefficient. RESULTS: There were 40 patients among whom
      15(37.5%) were males and 25(62.5%) were females with an overall mean age of
      55.68+/-14.4 years. There was a significant inverse relationship between hepcidin
      and haemoglobin levels (p<0.05). There were significant correlations between
      hepcidin with iron status, nutritional and inflammatory markers such as ferritin,
      Total iron binding capacity, albumin and interleukin 6 (p<0.05 each).
      CONCLUSIONS: Hepcidin had negative correlation with haemoglobin level in stage 4
      chronic kidney disease patients with adequate iron stores, which could be
      effective in the development of anaemia in such patients.

PMID- 25976566
TI  - Postoperative pain management in the surgical wards of a tertiary care hospital
      in Peshawar.
AB  - OBJECTIVE: To assess levels of postoperative pain with reference to
      internationally validated protocols. METHODS: The hospital-based survey of
      postoperative patients was conducted from February 2012 to April 2012 in the
      surgical wards of Rehman Medical Institute, Peshawar. A questionnaire was devised
      incorporating internationally validated World Health Organisation pain scoring
      system to assess the level of pain control. The severity of postoperative pain
      was further evaluated by correlating it with various variables. RESULTS: Of the
      210 patients interviewed, 80(38%) were males with a mean age of 44.16+/-20.37 and
      130(62%) were females with a mean age of 36.47+/-14.39. Overall, 84(40%) patients
      experienced mild pain, 82(39%) experienced moderate pain and 33(16%) experienced
      severe pain, while only 11(5%) experienced no pain when assessed within the first
      24 hours following surgery. The same patients when interviewed within the 48
      hours following surgery showed 117(56%) were in mild pain, 72(34%) in moderate to
      severe pain and 21(10%) had no pain. CONCLUSIONS: The achievement of absolute no
      pain for all patients in the post-operative phase is next to impossible, but it
      should remain the ultimate target.

PMID- 25976567
TI  - Effects of line type blood-liquid warmer on two different infusion sets.
AB  - OBJECTIVE: To investigate the source of 'bubbles' in infusion sets which were
      caused by the 'line type' blood-liquid warmers used in operation rooms to prevent
      hypothermia. METHODS: The experimental study was conducted from August to
      September 2012 at the Thoracic Surgery Department of Dokuz Eylul University,
      Izmir, Turkey, by warming liquids in the operation room experimentally in a
      setting similar to clinical routine. Initially, 0.9% sodium chloride solution was
      infused using S-line blood-liquid warmers with Medisetin patients who were placed
      in Group M). The IPC Group had Intrafix Primeline Confortset at a rate of
      350ml/hour in the operating room. The initiation time and level of bubble
      formation, temperatures of the operation room, infusion liquid, S-line device,
      line of the device, and the liquid at the outflow were recorded. Data was
      analysed with SPSS 15. RESULTS: The two groups had 10 subjects each. The
      temperatures of the working area, the liquid before and after being placed in the
      warming device, the proximal-middle and distal parts of the line and the set
      temperature on the screen of the device were similar and the difference between
      them was not statistically significant (p>0.05). While no bubble formation was
      observed in Group IPC, bubbles were formed after 9.80+/-0.78 minutes and the
      level of bubble formation was close to 3 in Group Mediset (2.80+/-1.03). The main
      difference between the two groups was di (2-ethylhexyl) phthalate content of
      Mediset. CONCLUSIONS: Infusion sets containing di(2-ethylhexyl) phthalate should
      not be used with warming devices in order to avoid toxic effects.

PMID- 25976568
TI  - Burden of chronic kidney disease in an urban city of Pakistan, a cross-sectional
      study.
AB  - OBJECTIVE: To estimate the prevalence of Chronic Kidney Disease in an urban city
      and to assess the risk factors associated with the condition. METHODS: The cross
      sectional study was carried out from June to December 2012 by arranging health
      camps for asymptomatic population in Karachi at busy shopping areas frequented by
      people of all socioeconomic classes. The camps provided free screening tests for
      the general public. Serum creatinine was checked and estimated Glomerular
      Filtration Rate was calculated using the Chronic Kidney Disease Epidemiology
      Collaboration equation. SPSS 17 was used for statistical analysis. RESULTS: Of
      the 301 subjects who came to the camps, 293(97%) had their serum creatinine
      checked. The age range was 30-80 years. Chronic Kidney Disease was found in
      75(25.60%)subjects. A significant relationship was found between the disease and
      Diabetes Mellitus and Hypertension (p=0.006). There was also a significant
      relationship between Hypertension and Diabetes with mean Glomerular Filtration
      Rate (p<0.001). CONCLUSIONS: In view of the prevalence rate of Chronic Kidney
      Disease, early screening and risk factor stratification is recommended.

PMID- 25976569
TI  - A cross sectional study on juvenile idiopathic arthritis in paediatric
      population.
AB  - OBJECTIVE: To determine the frequency of common subtypes of juvenile idiopathic
      arthritis among paediatric population. METHODS: The cross-sectional study was
      conducted at the National Institute of Child Health, Karachi, from January to
      June, 2010, and comprised children below 16 years of age with arthritis in one or
      more joints for at least 6 weeks. Physical examination was done and detailed
      history was recorded. When >5 joints of the body were involved, it was considered
      polyarthritis. If <4 joints were involved, it was pauciarticular arthritis.
      RESULTS: Of the 95 cases in the study, 52(54.7%) were girls and 43(45.3%) were
      boys, with an overall mean age of 11+/-1.2 years. Polyarticular arthritis was
      found in 51(53.7%) subjects and pauciarticular arthritis in 44(46.3%). Out of 43
      boys, 27(62.8%) had pauciarticular, while 35(67.3%) of the 52 girls had
      polyarticular arthritis. CONCLUSIONS: Polyarticular arthritis was the most common
      sub-type. Proportion of polyarticular arthritis was high in female children,
      while pauciarticular arthritis was high in male children.

PMID- 25976570
TI  - Experience of CyberKnife Robotic Radiosurgery in treating intra and extra-cranial
      tumours: A review of outcomes.
AB  - OBJECTIVE: To determine the success rate and complication of CyberKnife Robotic
      Radiosurgery for treating intracranial and extra cranial tumours. METHODS: The
      cross-sectional observational study was carried out at the Department of
      CyberKnife Robotic Radiosurgery at the Jinnah Postgraduate Medical Centre,
      Karachi, and reviewed data related to a year from December 2012 to December 2013.
      Patients referred from different hospitals within and outside Pakistan for
      stereotactic radiosurgery were included. The patients had benign tumours less
      than 7cm size, post-operative residual tumour and recurrent tumour with post
      radiotherapy. Patients were followed up every three months with contrast magnetic
      resonance imaging. Radiosurgery was considered successful if patients improved
      clinically with radiologically stable disease or if there was interval reduction
      in the size of tumour. SPSS 17 was used for data analysis. RESULTS: Initially,
      260 patients were selected, but 9(3.5%) were lost, and the final sample size was
      251(96.5%). Clinically successful outcome results were seen in 225(90%) patients,
      while 8(3%) showed no change in symptoms and 18(7%) patients' follow-up is
      awaited. Radiological improvement was noted in 218(87%); stable disease in
      138(55%) and 80(32%) cases showed more than 30% reduction in size after 6-12
      months of follow-up. Only 5(2%) cases showed subtle increase in size within 3
      month interval due to post-radiation oedema. Acute transient post-radiation
      changes were seen in 25(10%) patients, sub-acute changes in 4(1.59%) and 1(0.3%)
      patient showed radionecrosis after 9-month interval. CONCLUSIONS: Cyberknife was
      an effective, safe and successful treatment alternative to surgery in benign and
      malignant tumours with low risk of post-radiotherapy complication compared to
      conventional radiation.

PMID- 25976571
TI  - Sleep quality among medical students of Karachi, Pakistan.
AB  - OBJECTIVE: To characterise sleep quality and assess degree of daytime sleepiness
      among medical students of Karachi. METHODS: The cross-sectional study was
      conducted between August and December 2013 and subjects were recruited from five
      haphazardly selected medical colleges in Karachi. A convenience sample of medical
      students underwent two validated self-administered questionnaires i.e. Pittsburgh
      Sleep Quality Index and Epworth Sleepiness Scale. SPSS 17 was used for
      statistical analysis. RESULTS: Of the 650 students approached, 504(77.5%)
      subjects completely filled out the questionnaires. Of them, 300(59.5%) were
      females and 204(40.5%) were males. Overall mean age was 20+/-1.4 years. Of them,
      199(39.5%) were classified as "Poor Sleepers". Poor sleep quality was associated
      with female gender (p <0.05), excessive daytime sleepiness (p <0.05), total hours
      slept (p <0.001) and sleep disturbances (p <0.001). Bed-timing analysis showed
      365(72%) students went to bed after midnight. CONCLUSIONS: Sleep quality among
      Pakistani medical students was significantly poor. Efforts must be directed
      towards proper sleep hygiene education.

PMID- 25976572
TI  - Role of oxidative injury in affecting the foetal & placental weights on exposure
      to tobacco smoke.
AB  - OBJECTIVE: To investigate the role of oxidative injury in affecting foetal and
      placental weights in mice by exposing them to tobacco smoke with or without
      supplementation with antioxidants. METHODS: The randomized control trial of
      pregnant mice at day one of gestation was conducted at Anatomy Department CPSP
      Regional Center Islamabad, from March 2005 to October 2005. The mice were divided
      into three groups: Group C had controls, while the two other groups, groups S and
      SV were exposed to secondary tobacco smoke in a whole body exposure chamber with
      and without supplementation with vitamins respectively. At term, the animals were
      sacrificed and the placentae and foetuses were weighed. The average values were
      calculated. The means for each group were analysed and the foetal placental ratio
      was calculated. SPSS 17 was used for statistical analysis. RESULTS: There were 44
      mice; 15(34%) each in S and SV groups, while Group C had 14(32%) mice who acted
      as the controls. The mean foetal weight in Group S was 0.65+/-0.52g which was
      significantly less (p<0.0001) than1.48+/-0.19g in Group C. The mean foetal weight
      in Group SV was 0.97+/-0.65g which was not significantly different from S
      (p=0.124). The mean placental weight in Group S was 0.16+/-0.02g which was
      significantly less than 0.21+/-0.05gin Group C (p=0.014). In Group SV it was
      significantly more than Group S (p<0.0001). The ratio of mean foetal and mean
      placental weights in the groups C, S and SV were 7.05, 3.92 and4.41 respectively.
      CONCLUSIONS: Prenatal exposure to tobacco smoke decreased the mean foetal and
      placental weights and the foetal-placental ratio. This may partly be attributed
      to oxidative injury induced by free radicals in the tobacco smoke as it is
      prevented to some extent by simultaneous administration of antioxidants.

PMID- 25976573
TI  - Bone mineral density comparison of total body, lumbar and thoracic: an
      exploratory study.
AB  - OBJECTIVE: To analyse the behaviour of bone mineral density (BMD) of total body,
      lumbar and thoracic spine, and compare it between different age-groups, ethnicity
      and gender as a secondary analysis of already published data of NHANES. METHODS:
      The study was done and compared data of the National Health and Nutrition
      Examination Survey which was done from 1999 to 2006. It comprised bone mineral
      density data of 26,215 subjects of age 8 years and over. The sample was divided
      into 10 age groups, 3 ethnicities and gender groups. All subjects had bodyweights
      not exceeding 300lb, and height not greater than 6'5''. Female subjects were non
      pregnant. SPSS 16 was used for statistical analysis. RESULTS: Of the total
      subjects, 7712 (29.41%) were Mexican Americans, 11236 (42.86%) were non-Hispanic
      whites and 7267 (27.73%) were non-Hispanic blacks. There were 13291 (50.69%)
      males, and each ethnic group also had approximately 50% males. The bone mineral
      density of non-Hispanic blacks was higher than the other two groups, whereas
      males of all ethnic groups and races had higher density then females of the same
      group. Bone mineral density of total body, lumbar and thoracic was significantly
      different. After 50 years of age, total body, lumbar and thoracic bone mineral
      density decreased in females but lumbar slightly increased in males, whereas
      thoracic remained stable and total body decreased. CONCLUSIONS: The bone mineral
      density of male and blacks was higher than female and non-black races in total
      body, lumbar and thoracic spine. The thoracic BMD was lower and might predict
      early fracture risk.

PMID- 25976574
TI  - Dengue knowledge and its management practices among physicians of major cities of
      Pakistan.
AB  - OBJECTIVE: To assess knowledge and practices related to dengue management among
      physicians. METHODS: The cross-sectional study was conducted at hospitals in
      Islamabad, Lahore, Faisalabad, Peshawar, Quetta and Karachi between June and
      December 2012Physicians from public and private sectors filled a self
      administered questionnaire about dengue knowledge and its management practices. A
      maximum score of 100 was assigned to the knowledge portion. Data was analysed
      using SPSS 15. RESULTS: A total of 400 subjects participated in the study;
      200(50%) each from public and private hospitals. Of them, 223(56%) were males;
      268(67%) were in the 21-30 years age bracket. The highest score was recorded in
      Quetta 67 followed by 65 in Karachi, 62 in Lahore, Faisalabad, Peshawar and 59 in
      Islamabad. Of the total, 200 (50%) were not aware that leucopenia is a criterion
      for diagnosing probable dengue. Similarly 140 (35%) did not know the criteria for
      diagnosing dengue haemorrhagic fever and warning signs of severe dengue. Total of
      204 (51%) were not aware of the criteria for discharging of the admitted cases.
      There was no significant difference between dengue knowledge of the physicians
      belonging to public and private sectors (p>0.05). CONCLUSIONS: Quite a large
      number of physicians lacked knowledge of probable diagnosis of dengue and
      appropriate time to discharge the patients.

PMID- 25976575
TI  - Evaluation of diploma in bioethics programme, Karachi, Pakistan: An educational
      research.
AB  - OBJECTIVE: To perform an outcome-based evaluation of the diploma programme
      initiated in 2006 at the Centre of Biomedical Ethics and Culture. METHODS: The
      broad based evaluation was done at the Centre of Biomedical Ethics and Culture,
      Sindh Institute of Urology and Transplantation, Karachi, from July 2011 to June
      2012 and comprised pass out batches from 2006 to 2010. Outcome logic model was
      applied through a questionnaire-based approach. Emails were sent to the
      graduates, containing a mix of closed and open-ended questions. Quantitative
      feedback was analysed for frequencies and percentages. Content analysis was
      conducted for open-ended responses. SPSS 19 was used for statistical analysis.
      RESULTS: Four batches had graduated in the five-year study period. A total of 50
      students had been enrolled, while 41(82%) graduated. Of them, 31(76%) graduates
      responded. Overall, 10(24%) graduates completed their Masters in bioethics, and
      16(39%) were involved in institutional ethics committee. All (100%) believed the
      diploma had increased their knowledge of ethics and they were involved in
      disseminating the acquired knowledge through presentations, seminars/conferences
      29(93.5%), teaching and awareness activities 22(71%). Besides, 28(90%)
      respondents believed their behaviour had changed and 27(87%)were improving the
      quality of work and environment, while 18(58%) had published related articles
      after their diploma. CONCLUSIONS: The programme was found to have achieved its
      objective during the first five years of its inception.

PMID- 25976576
TI  - Effect of coenzyme Q10 on glycaemic control, oxidative stress and adiponectin in
      type 2 diabetes.
AB  - OBJECTIVE: To assess the effects of Coenzyme Q10 supplementation on glycaemic
      control, oxidative stress and adiponectin levels in people with type 2 diabetes.
      METHODS: The randomised, single-blind, placebo-controlled study was conducted in
      the city of Shiraz, Iran, in 2012 and comprised type 2 diabetes subjects
      recruited from various health facilities. Subjects and controls received 100mg
      Coenzyme Q10 or placebo twice a day for eight weeks respectively. A variety of
      measurements were made at baseline and at the end of the intervention. These
      included measuring markers of glycaemic control (fasting blood glucose and
      glycated haemoglobin); a marker of oxidative stress (malondialdehyde); and an
      anti-inflammatory marker (adiponectin). SPSS 15 was used for statistical
      analysis. RESULTS: Of the 52 patients, 28(54%) were male and 24(46%) were female,
      with an overall mean age of 51.73+/-7.34 years. There were 16(62% male and
      10(39%) females in the intervention group, and 12(46%) male and 14(54%) female
      subjects in the control group. Among the cases, Coenzyme Q10 resulted in a
      significant reduction in malondialdehyde levels (p=0.04). However, the difference
      within the controls for this factor was not significant (p>-0.05). Moreover,
      fasting blood glucose, glycated haemoglobin and adiponectin levels showed no
      significant differences within or between the groups (p>0.05 each). CONCLUSIONS:
      Coenzyme supplementation may reduce oxidative stress in type 2 diabetics.
      However, it may not have any effects on glycaemic control and adiponectin levels.

PMID- 25976577
TI  - Menopausal symptoms: prevalence, severity and correlation with sociodemographic
      and reproductive characteristics. A cross sectional community based survey from
      rural Sindh Pakistan.
AB  - OBJECTIVE: To determine prevalence and severity of menopausal symptoms and to
      investigate any correlation of sociodemographic and reproductive characteristics
      with menopausal symptoms in rural women. METHODS: The cross-sectional study was
      conducted in 2007-08 in rural Sindh, Pakistan, and comprised women of age 40-70
      years who were selected through multistage random sampling. Sociodemographic
      information was collected on a predesigned proforma. Menopause Rating Scale was
      used to collect information regarding the prevalence and severity of menopausal
      symptoms. Multivariate logistic regression was used to adjust prevalence odds
      ratio for demographic and reproductive characteristics. RESULTS: From among a
      population of 525,082, the study selected 3062(0.5%) women. The prevalence of
      menopausal symptoms was mostly higher except bladder problems 1138(37.7%) and
      dryness of vagina 1008(34%). The frequency of symptoms - all mild in nature -
      were hot flushes 1287(42%), sleep problems 1251(40.9%), depressive mode
      1169(38.2%), physical and mental exertion 1169(38.2%), and muscle and joint pain
      861(28.1%). Significant association of the symptoms was found with age, education
      and menopausal status (p<0.05 each). CONCLUSIONS: The prevalence of most of the
      menopausal symptoms was high except for bladder problems and dryness of vagina.
      Majority of the symptoms were categorised as mild.

PMID- 25976578
TI  - Teaching of medical humanities in medical universities of Pakistan.

PMID- 25976579
TI  - Fear of falling in elderly people living in a nursing home -- perspective from
      Manisa.
AB  - Our study aimed to determine the level of fear of falling in elderly nursing home
      residents. The research population consisted of all the elderly residents of
      Manisa Municipal Nursing Home between November 2011 and February 2012. The 76
      elderly people who agreed to participate were included in the study. A
      demographics form and the Tinetti Falls Efficacy Scale were used in data
      collection. The statistical analysis of the data was performed using SPSS 15.0,
      using percentage calculations, the t-test and Cronbach's alpha. The mean score on
      the Tinetti Falls Efficacy Scale for elderly individuals was found to be 4.57 +/-
      3.80. 57.9% of the old people feared falling while taking a bath, 59.2% while
      going to bed or getting up, and 53.6% while sitting down or getting up from a
      chair. It was found that mean fear of falling scores were significantly higher in
      elderly individuals with chronic diseases, sleep problems and urinary
      incontinence. 

PMID- 25976580
TI  - Opinions of university students on honour killings: Perspective from Islamabad
      and Rawalpindi.
AB  - Honour killing incidents have been reported from every province of Pakistan. In
      2014 a pregnant woman was killed in front of Lahore High Court, by her family
      members, in the name of honour. This study was conducted to determine the
      perspective of university students on honour killing with specific reference to
      one such killing incident in Lahore. Cumulatively, 989 students participated in
      the survey. Compared with female students, male students were less likely to
      agree and were more unequivocal that a woman has a right to marry any man she
      wants despite her family's disapproval, in a statistically significant manner.
      Similarly, male students were statistically significantly more likely to report
      that killing in the name of honour is always justified and were less equivocal
      about it compared to female students. Nonetheless, cumulatively 824 (83.3%)
      students believed that killing in the name of honour is not always justified. 

PMID- 25976581
TI  - Hair dye poisoning and rhabdomyolysis.
AB  - Hair dye ingestion is a rare cause of toxicity in Pakistan. We are presenting the
      case report of a 55 year old male who presented with accidental hair dye
      ingestion and developed laryngeal oedema requiring emergent tracheostomy. He had
      also developed aspiration pneumonitis and chemical oesophagitis. However, the
      most alarming manifestation was rhabdomyolysis. Hair dye toxicity can be fatal if
      not recognized early. There is no antidote available. Rhabdomyolysis is a
      complication and needs to be managed aggressively in order to prevent long term
      morbidity. 

PMID- 25976582
TI  - The calcium invasion: Calciphylaxis in Lupus.
AB  - Calciphylaxis is a poorly understood and highly morbid syndrome of vascular
      calcification and skin necrosis. We describe the case of a 52-year old woman with
      systemic lupus erythematosus (SLE), inappropriately treated with oral steroids
      for 18-years who developed renal impairment followed by skin necrosis and
      gangrene of right hand. She had subcutaneous calcium deposition with bilateral
      renal stones and widespread vascular calcifications. She was diagnosed with
      calciphylaxis and in spite of treatment died of a myocardial infarction. 

PMID- 25976583
TI  - Otitis complicated by Jacod's syndrome with unusal facial nerve involvement: Case
      report and review of literature.
AB  - Otitis media is a well-known condition and its infra-temporal and intracranial
      complications are extremely rare because of the widespread usage of antibiotic
      treatment. We report a case of 63-year-old female with complaints of right-sided
      facial pain and diplopia. She had a history of acute otitis media before 4 months
      of admission to our neurology unit. Neurological examination showed that total
      ophthalmoplegia with ptosis, mydriasis, decreased vision and loss of pupil reflex
      on the right side. In addition, there was involvement of 5th and 7th cranial
      nerves. Neurological and radiological follow-up examinations demonstrated Jacod's
      Syndrome with unusual facial nerve damage and infection in aetiology. Sinusitis
      is the most common aetiology, but there are a few cases reported Jacod's Syndrome
      originating from otitis media. 

PMID- 25976584
TI  - An unusual location and presentation of a usual pathology-Colloid cyst of fourth
      ventricle presenting as spontaneous rhinorrhea.
AB  - Colloid cysts are relatively rare benign intracranial lesions preferentially
      located within the third ventricle. There are only a few reports in which they
      have been found to be ectopic, such as in the fourth ventricle. A young female
      presented on with spontaneous non-traumatic cerebrospinal fluid (CSF) rhinorrhoea
      for three months which was positional in nature, relieved temporarily by neck
      flexion. Magnetic resonance imaging (MRI) scan showed a focal well-defined
      rounded cystic lesion along the fourth ventricle, showing subtle peripheral rim
      enhancement. Significant hydrocephalus was also noted. A suboccipital craniotomy
      and total excision of the lesion was done. Postoperatively, the patient recovered
      quickly with no neurological deficits. Her rhinorrhoea was completely cured.
      Histopathology was consistent with a colloid cyst. Colloid cyst is rarely found
      in infratentorial location. However, such a rare diagnosis has to be considered
      in the differential diagnosis in patients who present with an infratentorial
      cystic lesion associated with spontaneous CSF rhinorrhoea. 

PMID- 25976585
TI  - Radiology and diabetes mellitus.
AB  - Diabetes mellitus (DM) is a major health concern globally, affecting almost every
      organ of the body. A major issue with DM is that a relatively large proportion of
      patients remain undiagnosed till the development of complications, many of which
      may cause permanent impairment. Therefore, early recognition of the radiological
      manifestations (of DM) is of utmost importance, so that the disease may be
      diagnosed and managed well in time. Some common and important radiological
      features encountered in practice are compiled in this article. 

PMID- 25976586
TI  - Initiating oral anti diabetic drug: alternatives to metformin.
AB  - While most published articles on oral anti diabetic therapy approve of metformin,
      few discuss what should be done if metformin is contraindicated or not tolerated.
      This article defines metformin intolerance, and discusses various pharmacological
      options available for persons with type 2 diabetes who cannot take metformin and
      do not accept/require insulin. 

PMID- 25976587
TI  - Energy drinks; a public health hazard for adolescents.

PMID- 25976588
TI  - Post-operative anxiety, depression and psychiatric support in patients undergoing
      hysterectomy: A cross sectional survey.
AB  - Hysterectomy is a frequently performed gynaecological procedure in Pakistan. This
      surgical procedure is a very stressful event for Pakistani women suffering from
      severe gynecological diseases and complications. It is also associated with a
      high incidence of anxiety and depression. Several studies in the West have
      reported an improvement in symptoms of depression and anxiety in patients
      undergoing hysterectomy. But this situation might be different in low resource
      countries like Pakistan where it is usually associated with myths, life
      threatening complications and obstetric abnormalities. Psychiatric support for
      these women is almost non-existent in general surgical settings. 

PMID- 25976590
TI  - How Do We Create the Best Pediatric Workforce? Questions Abroad and at Home.

PMID- 25976589
TI  - Another Reason to Avoid Second-Hand Smoke.

PMID- 25976591
TI  - The role of social support on the relationship of depressive symptoms to
      medication adherence and self-care activities in adults with type 2 diabetes.
AB  - AIM: To examine the mediating role of social support on the relationship of
      depressive symptoms to medication adherence and self-care activities in Korean
      adults. BACKGROUND: Recent evidence suggests that higher levels of social support
      are associated with improved medication adherence and self-care activities;
      however, the role of social support on the relationship of depressive symptoms to
      medication adherence and self-care activities is less well understood. DESIGN: A
      cross-sectional survey. METHODS: The data were collected from 311 Korean adults
      with type 2 diabetes who were taking hypoglycaemic agents in the period 2012
      2013. Depressive symptoms, social support, medication adherence and self-care
      activities were assessed using structured questionnaires. Multiple regression
      analysis with adjustment for covariates and the Sobel test were used to examine
      the mediating effect of social support on the relationship of depressive symptoms
      to medication adherence and self-care activities. RESULTS: There were
      statistically significant differences by subgroups with and without depressive
      symptoms in social support, medication adherence and self-care activities of
      diet, physical activity and stress management. The Sobel test confirmed that
      social support mediated the effect of depressive symptoms on medication adherence
      and self-care activities of diet, physical activity and stress management.
      CONCLUSION: The evidence from this study suggests that social support-enhancing
      interventions that also manage depressive symptoms may be more timely and
      effective than interventions that target depressive symptoms alone in promoting
      adherence to medication adherence and self-care activities in this population.

PMID- 25976592
TI  - Simultaneous detection of Tomato spotted wilt virus, Dahlia mosaic virus and
      Chrysanthemum stunt viroid by multiplex RT-PCR in dahlias and their distribution
      in Japanese dahlias.
AB  - Tomato spotted wilt virus (TSWV), Dahlia mosaic virus (DMV) and Chrysanthemum
      stunt viroid (CSVd) are economically important viruses and viroid that infect
      cultivated dahlias. Prior to this investigation, no multiplex RT-PCR assay for
      the detection of dahlia virus and viroid infections existed. In this study, we
      report the development of a multiplex RT-PCR that simultaneously detects TSWV,
      DMV and CSVd infections in dahlias. In addition, a simple RT-PCR method that does
      not require RNA extraction, microtissue direct RT-PCR, could be used to prepare
      samples for analysis by this multiplex RT-PCR. A field survey validated our
      results, indicating that TSWV was the dominant virus found in the Kansai region,
      DMV in the Tohoku and Kyushu regions, and CSVd in the Hokkaido region. This
      method represents a rapid, sensitive and cost effective approach to diagnose
      viral infections in dahlias. SIGNIFICANCE AND IMPACT OF THE STUDY: The multiplex
      RT-PCR assay described in this study is the first report of simultaneous
      detection of virus and viroid in dahlia. This method represents a rapid,
      sensitive and cost effective approach to diagnose viral infections in dahlias. A
      field survey validated our results, indicating that TSWV was the dominant virus
      found in the Kansai region, DMV in the Tohoku and Kyushu regions and CSVd in the
      Hokkaido region.

PMID- 25976593
TI  - Enzymatic cell disruption of microalgae biomass in biorefinery processes.
AB  - When employing biotechnological processes for the procurement of biofuels and bio
      products from microalgae, one of the most critical steps affecting economy and
      yields is the "cell disruption" stage. Currently, enzymatic cell disruption has
      delivered effective and cost competitive results when compared to mechanical and
      chemical cell disruption methods. However, the introduction of enzymes implies
      additional associated cost within the overall process. In order to reduce this
      cost, autolysis of microalgae is proposed as alternative enzymatic cell
      disruption method. This review aims to provide the state of the art of enzymatic
      cell disruption treatments employed in biorefinery processes and highlights the
      use of endopeptidases. During the enzymatic processes of microalgae life cycle,
      some lytic enzymes involved in cell division and programmed cell death have been
      proven useful in performing cell lysis. In this context, the role of
      endopeptidases is emphasized. Mirroring these natural events, an alternative cell
      disruption approach is proposed and described with the potential to induce the
      autolysis process using intrinsic cell enzymes. Integrating induced autolysis
      within biofuel production processes offers a promising approach to reduce overall
      global costs and energetic input associated with those of current cell disruption
      methods. A number of options for further inquiry are also discussed.

PMID- 25976594
TI  - Periprosthetic Fractures: A Common Problem with a Disproportionately High Impact
      on Healthcare Resources.
AB  - The present study evaluated the frequency of periprosthetic fractures and tested
      the hypothesis that this population's demographics and outcomes are unique as
      compared with other arthroplasty patients. The National Hospital Discharge Survey
      provided the raw data. Individuals admitted with a primary TKA, primary THA, or
      revision TJA were selected. Annual rates were then calculated and demographics
      and outcomes compared. 30,624 patients were reviewed. The proportion of
      admissions for periprosthetic fractures ranged from 4.2% to 7.4% annually. As
      compared to patients admitted for other TJA diagnoses, individuals admitted with
      periprosthetic fracture were older, were more often female, were more often
      admitted emergently/urgently, had longer lengths of stay, had higher rates of
      discharge to places other than home, and had a significantly elevated mortality. 

PMID- 25976595
TI  - Which Tibial Tray Design Achieves Maximum Coverage and Ideal Rotation: Anatomic,
      Symmetric, or Asymmetric? An MRI-based study.
AB  - Two goals of tibial tray placement in TKA are to maximize coverage and establish
      proper rotation. Our purpose was to utilize MRI information obtained as part of
      PSI planning to determine the impact of tibial tray design on the relationship
      between coverage and rotation. MR images for 100 consecutive knees were uploaded
      into PSI software. Preoperative planning software was used to evaluate 3
      different tray designs: anatomic, symmetric, and asymmetric. Approximately
      equally good coverage was achieved with all three trays. However, the anatomic
      compared to symmetric/asymmetric trays required less malrotation (0.3 degrees  vs
      3.0/2.4 degrees ; P < 0.001), with a higher proportion of cases within 5 degrees 
      of neutral (97% vs 73/77%; P < 0.001). In this study, the anatomic tibia
      optimized the relationship between coverage and rotation. 

PMID- 25976596
TI  - Editorial: Extracellular vesicles: a paradigm shift in how we think about cell
      cell communication.

PMID- 25976597
TI  - Editorial: Molecular neuroprotection.

PMID- 25976598
TI  - Neurotransmitter changes during interference task in anterior cingulate cortex:
      evidence from fMRI-guided functional MRS at 3 T.
AB  - Neural activity as indirectly observed in blood oxygenation level-dependent
      (BOLD) response is thought to reflect changes in neurotransmitter flux. In this
      study, we used fMRI-guided functional magnetic resonance spectroscopy (MRS) to
      measure metabolite/BOLD associations during a cognitive task at 3 T. GABA and
      glutamate concentration in anterior cingulate cortex (ACC) were determined by
      means of MRS using the SPECIAL pulse sequence before, during and after the
      performance of a manual Stroop task. MRS voxel positions were centred around
      individuals' BOLD activity during Stroop performance. Levels of GABA and
      glutamate showed inverted U-shape patterns across measurement time points
      (before, during, and after task), glutamine increased linearly and total creatine
      did not change. The GABA increase during task performance was associated with ACC
      BOLD signal changes in both congruent and incongruent Stroop conditions. Using an
      fMRI-guided MRS approach, an association between induced inhibitory
      neurotransmitter increase and BOLD changes was observed. The proposed procedure
      might allow the in vivo investigation of normal and dysfunctional associations
      between neurotransmitters and BOLD signal crucial for cerebral functioning.

PMID- 25976600
TI  - The Precision of Pulmonary Artery Catheter Bolus Thermodilution Cardiac Output
      Measurements Varies With the Clinical Situation.
AB  - OBJECTIVE: To investigate the effects of ventilatory mode, injectate temperature,
      and clinical situation on the precision of cardiac output measurements. DESIGN:
      Randomized, prospective observational study. SETTING: Single university hospital.
      PARTICIPANTS: Forty patients undergoing planned cardiac surgery, receiving a
      pulmonary artery catheter according to institutional routine. INTERVENTIONS:
      Cardiac output was measured at 4 predefined time points during the perioperative
      patient course, twice during controlled and twice during spontaneous ventilation,
      using 2 blocks of 8 measurement replications with cold and tepid injectate in
      random order. MEASUREMENTS AND MAIN RESULTS: The data were analyzed using a
      hierarchical linear mixed model. Clinical precision was determined as half the
      width of the 95% confidence interval for the underlying true value. The single
      measurement precision measured in 2 different clinical situations for each
      temperature/ventilation combination was 8% to 10%, 11% to 13%, 13% to 15%, and
      23% to 24% in controlled ventilation with cold injectate, controlled ventilation
      with tepid injectate, spontaneous breathing with cold injectate, and spontaneous
      breathing with tepid injectate, respectively. Tables are provided for the number
      of replications needed to achieve a certain precision and for how to identify
      significant changes in cardiac output. CONCLUSIONS: Clinical precision of cardiac
      output measurements is reduced significantly during spontaneous relative to
      controlled ventilation. The differences in precision between repeated measurement
      series within the temperature/ventilation combinations indicate influence of
      other situation-specific factors not related to ventilatory mode. Compared with
      tepid injectate in patients breathing spontaneously, the precision is 3-fold
      better with cold injectate and controlled ventilation.

PMID- 25976599
TI  - Enhanced somatic embryogenesis in Theobroma cacao using the homologous BABY BOOM
      transcription factor.
AB  - BACKGROUND: Theobroma cacao, the chocolate tree, is an important economic crop in
      East Africa, South East Asia, and South and Central America. Propagation of elite
      varieties has been achieved through somatic embryogenesis (SE) but low
      efficiencies and genotype dependence still presents a significant limitation for
      its propagation at commercial scales. Manipulation of transcription factors has
      been used to enhance the formation of SEs in several other plant species. This
      work describes the use of the transcription factor Baby Boom (BBM) to promote the
      transition of somatic cacao cells from the vegetative to embryonic state.
      RESULTS: An ortholog of the Arabidopsis thaliana BBM gene (AtBBM) was
      characterized in T. cacao (TcBBM). TcBBM expression was observed throughout
      embryo development and was expressed at higher levels during SE as compared to
      zygotic embryogenesis (ZE). TcBBM overexpression in A. thaliana and T. cacao led
      to phenotypes associated with SE that did not require exogenous hormones. While
      transient ectopic expression of TcBBM provided only moderate enhancements in
      embryogenic potential, constitutive overexpression dramatically increased SE
      proliferation but also appeared to inhibit subsequent development. CONCLUSION:
      Our work provides validation that TcBBM is an ortholog to AtBBM and has a
      specific role in both somatic and zygotic embryogenesis. Furthermore, our studies
      revealed that TcBBM transcript levels could serve as a biomarker for
      embryogenesis in cacao tissue. Results from transient expression of TcBBM provide
      confirmation that transcription factors can be used to enhance SE without
      compromising plant development and avoiding GMO plant production. This strategy
      could compliment a hormone-based method of reprogramming somatic cells and lead
      to more precise manipulation of SE at the regulatory level of transcription
      factors. The technology would benefit the propagation of elite varieties with low
      regeneration potential as well as the production of transgenic plants, which
      similarly requires somatic cell reprogramming.

PMID- 25976601
TI  - Determinants of Transcutaneous Ear Lobe CO2 Tension (PtCO2) at 37 degrees C
      During On-Pump Cardiac Surgery.
AB  - OBJECTIVE: There are no available criteria for determining the optimal flow rate
      and mean arterial pressure level in patients undergoing cardiopulmonary bypass
      (CPB). Transcutaneous carbon dioxide tension (PtCO2) has been proposed for
      microcirculation monitoring and it could be useful for guiding hemodynamic
      optimization under CPB. The goal of this exploratory study was to determine the
      factors that influence PtCO2 variations during CPB. DESIGN: Cutaneous ear lobe
      CO2 tension was monitored along with hemodynamic parameters every 10 minutes
      during CPB, until aortic unclamping. SETTING: French university teaching
      hospital. PARTICIPANTS: Patients scheduled for cardiac surgery requiring CPB were
      prospectively included. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A
      total of 41 patients were included (520 observations). There was a statistically
      significant association between PaCO2 and PtCO2 (beta = 0.493 [0.154-0.832], p =
      0.043), mostly when PaCO2 was outside the normal range. When PaCO2 was normal,
      PtCO2 was inversely correlated with mean arterial pressure (after adjustment for
      PaCO2 and body temperature: Beta -0.245, SE = 0.037, p<0.001) but not with CPB
      flow rate (p = 0.11). CONCLUSION: The factors that influence PtCO2 during CPB
      cardiac surgery are PaCO2, body temperature, and mean arterial pressure. When
      PaCO2 is normal, a PtCO2 elevation might be explained by insufficient mean
      arterial pressure. Whether low PtCO2 values during CPB should trigger the
      administration of vasoconstrictors remains to be evaluated.

PMID- 25976602
TI  - Preoperative Echocardiographic Parameters of Diastolic Dysfunction Did Not
      Provide a Predictive Value for Postoperative Atrial Fibrillation in Lung and
      Esophageal Cancer Surgery.
AB  - OBJECTIVE: To evaluate the predictive value of preoperative transthoracic
      echocardiography in the development of postoperative atrial fibrillation after
      non-cardiac thoracic surgery. DESIGN: This was a retrospective study. SETTING:
      Academic hospital. PARTICIPANTS: A total of 703 adult patients with non-small
      cell lung cancer. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Retrospective data of 177 non-cardiac thoracic surgical oncologic patients
      undergoing lung or esophageal cancer surgery with preoperative transthoracic
      echocardiograms (TTE) (within 30 days before surgery) were analyzed. The Wilcoxon
      rank sum test was used to evaluate the difference in continuous variables.
      Fisher's exact test or the chi-square test was used to evaluate the association
      between two categoric variables. Logistic regression models were used for
      multivariate analysis to include important and significant covariates. Among the
      demographic and echocardiographic variables measured age, systemic hypertension,
      e' septal, e' lateral and E/e' ratio were significantly different between
      patients who would develop postoperative atrial fibrillation (POAF) and those who
      did not. The logistic regression models only identify age as a predictor factor
      of POAF. CONCLUSIONS: These results were similar to those published elsewhere on
      POAF incidence and risk factors. The preoperative echocardiographic variables in
      this study did not provide predictive value for POAF in non-cardiac thoracic
      surgery.

PMID- 25976603
TI  - Effect of Jaw Thrust on Transesophageal Echocardiography Probe Insertion and
      Concomitant Oropharyngeal Injury.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of jaw thrust on
      transesophageal echocardiography probe insertion and concomitant oropharyngeal
      injury. DESIGN: A prospective, randomized study SETTING: Medical center governed
      by a university hospital PARTICIPANTS: Forty-two adult patients undergoing
      cardiovascular surgery were included. INTERVENTIONS: After the induction of
      anesthesia, a transesophageal echocardiography probe was inserted using an
      anterior jaw lift technique (conventional group, n = 21) or a jaw thrust-assisted
      technique (jaw thrust group, n = 21). MEASUREMENTS AND MAIN RESULTS: The
      incidence of oropharyngeal injury, number of insertion attempts, blood on the
      probe tip, and presence of persistent oropharyngeal bleeding were evaluated. In
      the conventional group, oropharyngeal injury occurred more frequently than in the
      jaw-thrust group (52.4% v 9.5%, respectively; p = 0.006). Regarding
      transesophageal echocardiography probe insertion, the conventional group required
      more attempts than the jaw-thrust group (p = 0.043). The incidence of blood on
      the probe tip was higher in the conventional group than in the jaw-thrust group
      (p = 0.020), but the presence of persistent oropharyngeal bleeding was similar
      between the 2 groups. CONCLUSIONS: The jaw-thrust maneuver facilitated the
      insertion of the transesophageal echocardiography probe and reduced concomitant
      oropharyngeal injury.

PMID- 25976604
TI  - Pneumonia and Inflammatory Arthritis Caused by Unusual Occupational Exposure or a
      Life-Threatening Infection Resulting From a More Commonly Encountered Mechanism?

PMID- 25976605
TI  - The Genetic Basis of Coronary Artery Disease and Atrial Fibrillation: A Search
      for Disease Mechanisms and Therapeutic Targets.

PMID- 25976606
TI  - Right Ventricular Depression After Cardiopulmonary Bypass for Valvular Surgery.
AB  - OBJECTIVE: To assess if right ventricular (RV) dysfunction is associated with
      increased mortality after cardiac surgery. DESIGN: Post-hoc analysis of a single
      center double-blind randomized controlled trial. SETTING: University hospital.
      PARTICIPANTS: A total of 120 patients undergoing simple or complex valvular
      surgery. INTERVENTIONS: Patients were randomized to receive intravenous
      amiodarone or placebo intraoperatively. As secondary analysis, patients were
      divided into those requiring or not requiring postoperative inotropic agents.
      MEASUREMENTS AND MAIN RESULTS: After cardiopulmonary bypass (CPB), there were
      significant increases in heart rate, cardiac index, systolic and mean arterial
      pressures, central venous pressure and pulmonary capillary wedge pressure with
      reduction in systemic vascular resistance (p<0.05). Right ventricular end
      systolic area became larger in those without inotropes and tricuspid annular
      plane systolic excursion was reduced in all patients; mitral annular systolic
      velocities were higher in patients receiving inotropes. Both right- and left
      sided Doppler signals were altered significantly after CPB, which may be
      attributed to increased filling pressure. Inotropic agents were required in 56
      patients after CPB (47%). The use of inotropic agents was associated with
      increased left and right atrial velocities (p<0.05). There were no differences in
      postoperative complications between groups; however, the number of deaths at 6
      years was increased in patients who received inotropes after CPB (p = 0.0247).
      CONCLUSIONS: The increases in right-sided dimensions after CPB are associated
      with reduction in RV function and increased biventricular filling pressure,
      suggesting worsening biventricular function and interventricular dependence.
      Inotropic medications were associated with unaltered RV dimensions and increased
      biatrial activity.

PMID- 25976607
TI  - Recreational alcohol use induces changes in the concentrations of choline
      containing compounds and total creatine in the brain: a (1)H MRS study of healthy
      subjects.
AB  - OBJECTIVE: It has previously been reported that even social alcohol consumption
      affects the magnetic resonance spectroscopy (MRS) signals of choline-containing
      compounds (tCho). The purpose of this study was to investigate whether the
      consumption of alcohol affects the concentrations of the metabolites tCho, N
      acetylaspartate, creatine, or myo-inositol and/or their T 2 relaxation times.
      MATERIALS AND METHODS: (1)H MR spectra were obtained at 3 T from a frontal white
      matter voxel of 25 healthy subjects with social alcohol consumption (between 0
      and 25.9 g/day). Absolute brain metabolite concentrations and T 2 relaxation
      times of metabolites were examined via MRS measurements at different echo times.
      Metabolite concentrations and their T 2 relaxation times were correlated with
      subjects' alcohol consumption, controlling for age. RESULTS: We observed positive
      correlations of absolute tCho and phosphocreatine and creatine (tCr)
      concentrations with alcohol consumption but no correlation between any metabolite
      T 2 relaxation time and alcohol consumption. CONCLUSIONS: This study shows that
      even social alcohol consumption affects the concentrations of tCho and tCr in
      cerebral white matter. Future studies assessing brain tCho and tCr levels should
      control for the confounding factor alcohol consumption.

PMID- 25976609
TI  - A coat with a clue.

PMID- 25976608
TI  - Proteomics approaches shed new light on hibernation physiology.
AB  - The broad phylogenetic distribution and rapid phenotypic transitions of mammalian
      hibernators imply that hibernation is accomplished by differential expression of
      common genes. Traditional candidate gene approaches have thus far explained
      little of the molecular mechanisms underlying hibernation, likely due to (1)
      incomplete and imprecise sampling of a complex phenotype, and (2) the forming of
      hypotheses about which genes might be important based on studies of model
      organisms incapable of such dynamic physiology. Unbiased screening approaches,
      such as proteomics, offer an alternative means to discover the cellular
      underpinnings that permit successful hibernation and may reveal previously
      overlooked, important pathways. Here, we review the findings that have emerged
      from proteomics studies of hibernation. One striking feature is the stability of
      the proteome, especially across the extreme physiological shifts of torpor
      arousal cycles during hibernation. This has led to subsequent investigations of
      the role of post-translational protein modifications in altering protein activity
      without energetically wasteful removal and rebuilding of protein pools. Another
      unexpected finding is the paucity of universal proteomic adjustments across organ
      systems in response to the extreme metabolic fluctuations despite the
      universality of their physiological challenges; rather each organ appears to
      respond in a unique, tissue-specific manner. Additional research is needed to
      extend and synthesize these results before it will be possible to address the
      whole body physiology of hibernation. 

PMID- 25976610
TI  - Quantitative accuracy of the simplified strong ion equation to predict serum pH
      in dogs.
AB  - BACKGROUND: Electrochemical approach to the assessment of acid-base states should
      provide a better mechanistic explanation of the metabolic component than methods
      that consider only pH and carbon dioxide. HYPOTHESIS/OBJECTIVES: Simplified
      strong ion equation (SSIE), using published dog-specific values, would predict
      the measured serum pH of diseased dogs. ANIMALS: Ten dogs, hospitalized for
      various reasons. METHODS: Prospective study of a convenience sample of a
      consecutive series of dogs admitted to the Massey University Veterinary Teaching
      Hospital (MUVTH), from which serum biochemistry and blood gas analyses were
      performed at the same time. Serum pH was calculated (Hcal+) using the SSIE, and
      published values for the concentration and dissociation constant for the
      nonvolatile weak acids (Atot and Ka ), and subsequently Hcal+ was compared with
      the dog's actual pH (Hmeasured+). To determine the source of discordance between
      Hcal+ and Hmeasured+, the calculations were repeated using a series of
      substituted values for Atot and Ka . RESULTS: The Hcal+ did not approximate the
      Hmeasured+ for any dog (P = 0.499, r(2) = 0.068), and was consistently more
      basic. Substituted values Atot and Ka did not significantly improve the accuracy
      (r(2) = 0.169 to <0.001). Substituting the effective SID (Atot-[HCO3-]) produced
      a strong association between Hcal+ and Hmeasured+ (r(2) = 0.977). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Using the simplified strong ion equation and the published
      values for Atot and Ka does not appear to provide a quantitative explanation for
      the acid-base status of dogs. Efficacy of substituting the effective SID in the
      simplified strong ion equation suggests the error lies in calculating the SID.

PMID- 25976612
TI  - Suggestions for automatic quantitation of endoscopic image analysis to improve
      detection of small intestinal pathology in celiac disease patients.
AB  - Although many groups have attempted to develop an automated computerized method
      to detect pathology of the small intestinal mucosa caused by celiac disease, the
      efforts have thus far failed. This is due in part to the occult presence of the
      disease. When pathological evidence of celiac disease exists in the small bowel
      it is visually often patchy and subtle. Due to presence of extraneous substances
      such as air bubbles and opaque fluids, the use of computerized automation methods
      have only been partially successful in detecting the hallmarks of the disease in
      the small intestine-villous atrophy, fissuring, and a mottled appearance. By
      using a variety of computerized techniques and assigning a weight or vote to each
      technique, it is possible to improve the detection of abnormal regions which are
      indicative of celiac disease, and of treatment progress in diagnosed patients.
      Herein a paradigm is suggested for improving the efficacy of automated methods
      for measuring celiac disease manifestation in the small intestinal mucosa. The
      suggestions are applicable to both standard and videocapsule endoscopic imaging,
      since both methods could potentially benefit from computerized quantitation to
      improve celiac disease diagnosis. 

PMID- 25976611
TI  - The eukaryotic translation initiation regulator CDC123 defines a divergent clade
      of ATP-grasp enzymes with a predicted role in novel protein modifications.
AB  - Deciphering the origin of uniquely eukaryotic features of sub-cellular systems,
      such as the translation apparatus, is critical in reconstructing eukaryogenesis.
      One such feature is the highly conserved, but poorly understood, eukaryotic
      protein CDC123, which regulates the abundance of the eukaryotic translation
      initiation eIF2 complex and binds one of its components eIF2gamma. We show that
      the eukaryotic protein CDC123 defines a novel clade of ATP-grasp enzymes
      distinguished from all other members of the superfamily by a RAGNYA domain with
      two conserved lysines (henceforth the R2K clade). Combining the available
      biochemical and genetic data on CDC123 with the inferred enzymatic function, we
      propose that the eukaryotic CDC123 proteins are likely to function as ATP
      dependent protein-peptide ligases which modify proteins by ribosome-independent
      addition of an oligopeptide tag. We also show that the CDC123 family emerged
      first in bacteria where it appears to have diversified along with the two other
      families of the R2K clade. The bacterial CDC123 family members are of two
      distinct types, one found as part of type VI secretion systems which deliver
      polymorphic toxins and the other functioning as potential effectors delivered to
      amoeboid eukaryotic hosts. Representatives of the latter type have also been
      independently transferred to phylogenetically unrelated amoeboid eukaryotes and
      their nucleo-cytoplasmic large DNA viruses. Similarly, the two other prokaryotic
      R2K clade families are also proposed to participate in biological conflicts
      between bacteriophages and their hosts. These findings add further evidence to
      the recently proposed hypothesis that the horizontal transfer of enzymatic
      effectors from the bacterial endosymbionts of the stem eukaryotes played a
      fundamental role in the emergence of the characteristically eukaryotic regulatory
      systems and sub-cellular structures.

PMID- 25976613
TI  - Oral administration of marine collagen peptides prepared from chum salmon
      (Oncorhynchus keta) improves wound healing following cesarean section in rats.
AB  - BACKGROUND: The goal of the present study was to investigate the wound-healing
      potential of marine collagen peptides (MCPs) from chum salmon skin administered
      to rats following cesarean section (CS). METHODS: Ninety-six pregnant Sprague
      Dawley rats were randomly divided into four groups: a vehicle group and three MCP
      groups. After CS, rats were intragastrically given MCPs at doses of 0, 0.13,
      0.38, 1.15 g/kg*bw, respectively. On postoperative days 7, 14, and 21, the
      uterine bursting pressure, skin tensile strength, hydroxyproline (Hyp)
      concentrations, and histological and immunohistochemical characteristics of the
      scar tissue were examined. RESULTS: In the MCP groups, the skin tensile strength,
      uterine bursting pressure, and Hyp were significantly higher than those in the
      vehicle group at all three time points (p<0.05). The formation of capillary,
      fibroblast, and collagen fiber, the expression of platelet-endothelial cell
      adhesion molecule-1, basic fibroblast growth factor, and transforming growth
      factor beta-1 were increased in the MCP groups (p<0.05). CONCLUSION: MCPs could
      accelerate the process of wounding healing in rats after CS.

PMID- 25976614
TI  - MR imaging findings of ovarian torsion correlate with pathological hemorrhagic
      infarction.
AB  - AIM: The aim of this study was to clarify the magnetic resonance (MR) imaging
      findings, including diffusion-weighted imaging (DWI), of hemorrhagic infarction
      of ovarian torsion. MATERIAL AND METHODS: Twelve patients presenting surgically
      confirmed ovarian masses with torsion were independently evaluated by two
      radiologists about the following MR findings: presence of ascites, uterine
      deviation, wall thickening on T2 weighted image (WI), recognition of twisted
      pedicle on T1/T2WI, and presence of wall enhancement of ovarian lesions on Gd
      T1WI. The signal intensities on T1WI and DWI were compared with those of the
      iliopsoas muscle and the nerve root, respectively. These MR findings were
      statistically compared between cases of ovarian torsion with histopathologically
      proven hemorrhagic infarction and those without. RESULTS: Pathologically,
      hemorrhagic infarction of the wall was confirmed in six of twelve cases. Ascites,
      uterine deviation and twisted pedicle were detected in most cases whether with or
      without hemorrhagic infarction. The complete absence of wall enhancement was
      observed in only one case with necrosis. A higher signal intensity of the wall
      compared to controls was observed in 4/6 and 5/6 cases with infarction on
      T1WI/DWI, respectively. This was not observed in any cases without infarction.
      Three out of five cystic lesions with hemorrhagic infarction showed irregular
      wall thickening on T2WI, and no cystic lesion without hemorrhagic infarction did.
      Smooth wall thickening was observed in 2/6 cases without hemorrhagic infarction.
      CONCLUSION: Pathological hemorrhagic infarction of ovarian torsion was associated
      with several MR imaging findings, including high signal intensity on T1WI/DWI,
      and irregular wall thickening on T2WI.

PMID- 25976615
TI  - Social, Psychological and Financial Burden on Caregivers of Children with Chronic
      Illness: A Cross-sectional Study.
AB  - OBJECTIVES: To explore social, psychological and financial burden on caregivers
      of chronically diseased children. METHODS: Participants were recruited from
      ambulatory and hospital areas in pediatrics department following informed
      consent. Parents who were caregivers of children 18 y or below in age with
      chronic illness were included. Socio-demographic details were collected using a
      semi structured questionnaire, adapted from Family Burden Interview Schedule
      (FBIS). The psychological well-being of caregivers was assessed using Patient
      Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7).
      Descriptive analysis and ANOVA was done for comparing mean scores of responses to
      analyze financial, psychological and social burden across different diagnosis.
      RESULTS: A total of 204 (89 females:115 males) participated. Only 27% were
      receiving some benefits from government or hospital side. No depressive symptoms
      were reported by 25% caregivers, while 37% reported mild and 38% moderate to
      severe depressive symptoms. No anxiety symptoms were reported by 33%, while 50%
      reported mild and 17% moderate to severe anxiety symptoms. No association was
      seen between gender of the caregiver and depressive or anxiety symptoms.
      Significantly higher financial and social burden was seen in cerebral palsy and
      cancer groups vis-a-vis other diseases, being least in thalassemia. Disruption of
      routine life was highest in cancer group caregivers followed by those in cerebral
      palsy group. CONCLUSIONS: Most caregivers reported moderate depressive symptoms
      and mild to moderate anxiety symptoms. Cerebral palsy caused more social and
      financial burden on family vis-a-vis thalassemia. Social and financial burden on
      families of remaining diseases was comparable.

PMID- 25976616
TI  - Community-acquired Pneumonia and its Complications.
AB  - Community-acquired pneumonia (CAP) remains a major cause of morbidity and
      mortality worldwide in developing and developed countries, and its incidence is
      highest among children less than 5-y-old. Over the last five years, several
      international and local guidelines have been updated with new evidence concerning
      the epidemiology, etiology, pathogenesis, treatment and prevention of pediatric
      CAP, but there are still several major problems that need to be standardised. The
      aim of this review is to consider the available data concerning the termination,
      epidemiology, microbiology and pathogenesis, clinical features, diagnosis and
      differential diagnosis, treatment, and complications of pediatric CAP. There
      still are many unanswered questions concerning the management of CAP, including
      its definition, the difficulty to identify its etiological agents, the emergence
      of drug, and the lack of introduction of vaccines against respiratory pathogens
      in developing countries. More research is required in various areas (including
      therapy of atypical agents), and further efforts are needed to increase
      vaccination in order to reduce the incidence of the disease. 

PMID- 25976617
TI  - P2X7 receptor stimulates breast cancer cell invasion and migration via the AKT
      pathway.
AB  - Purinergic signaling has been implicated in the regulation of many cellular
      processes. A high concentration of ATP has been observed in the tumor
      microenvironment, suggesting a possible role of extracellular ATP in tumor
      progression. The P2X7 receptor, which belongs to the ligand-gated ion channel
      receptor family, is involved in tumor development and metastasis. In the present
      study, we found that extracellular ATP stimulated the invasion and migration of
      human T47D breast cancer cells, in a dose-dependent manner. BzATP (ATP analogue),
      but not ADP, also promoted invasion and migration. We further found that the P2X7
      receptor was highly expressed in the T47D cells. After knockdown of the P2X7
      receptor, ATP-stimulated invasion and migration were markedly inhibited.
      Moreover, activation of the P2X7 receptor by ATP downregulated the protein level
      of E-cadherin and upregulated the production of MMP-13. In addition, ATP time
      dependently induced the activation of AKT via the P2X7 receptor, and the AKT
      pathway was required for the ATP-mediated invasion and migration. Taken together,
      our results revealed that activation of the P2X7 receptor by ATP promotes breast
      cancer cell invasion and migration, possibly via activation of the AKT pathway
      and regulation of E-cadherin and MMP-13 expression. Therefore, the P2X7 receptor
      may be a useful therapeutic target for the treatment of breast cancer.

PMID- 25976619
TI  - Alginate gel particles-A review of production techniques and physical properties.
AB  - The application of hydrocolloid gel particles is potentially useful in food,
      chemical, and pharmaceutical industries. Alginate gel particles are one of the
      more commonly used hydrocolloid gel particles due to them being biocompatible,
      nontoxic, biodegradable, cheap, and simple to produce. They are particularly
      valued for their application in encapsulation. Encapsulation in alginate gel
      particles confers protective benefits to cells, DNA, nutrients, and microbes.
      Slow release of flavors, minerals, and drugs can also be achieved by
      encapsulation in gel particles. The particle size and shape of the gel particles
      are crucial for specific applications. In this review, current methods of
      producing alginate gel particles will be discussed, taking into account their
      advantages, disadvantages, scalability, and impact on particle size. The physical
      properties of alginate gel particles will determine the effectiveness in
      different application conditions. This review will cover the current
      understanding of the alginate biopolymer, gelation mechanisms and factors
      affecting release properties, gel strength, and rheology of the alginate gel
      particle systems.

PMID- 25976618
TI  - Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic
      activity and granule cell dematuration in the dentate gyrus.
AB  - BACKGROUND: Chronic treatment with selective serotonin (5-HT) reuptake inhibitors
      (SSRIs) facilitates adult neurogenesis and reverses the state of maturation in
      mature granule cells (GCs) in the dentate gyrus (DG) of the hippocampus. Recent
      studies have suggested that the 5-HT4 receptor is involved in both effects.
      However, it is largely unknown how the 5-HT4 receptor mediates neurogenic effects
      in the DG and, how the neurogenic and dematuration effects of SSRIs interact with
      each other. RESULTS: We addressed these issues using 5-HT4 receptor knockout (5
      HT4R KO) mice. Expression of the 5-HT4 receptor was detected in mature GCs but
      not in neuronal progenitors of the DG. We found that chronic treatment with the
      SSRI fluoxetine significantly increased cell proliferation and the number of
      doublecortin-positive cells in the DG of wild-type mice, but not in 5-HT4R KO
      mice. We then examined the correlation between the increased neurogenesis and the
      dematuration of GCs. As reported previously, reduced expression of calbindin in
      the DG, as an index of dematuration, by chronic fluoxetine treatment was observed
      in wild-type mice but not in 5-HT4R KO mice. The proliferative effect of
      fluoxetine was inversely correlated with the expression level of calbindin in the
      DG. The expression of neurogenic factors in the DG, such as brain derived
      neurotrophic factor (Bdnf), was also associated with the progression of
      dematuration. These results indicate that the neurogenic effects of fluoxetine in
      the DG are closely associated with the progression of dematuration of GCs. In
      contrast, the DG in which neurogenesis was impaired by irradiation still showed
      significant reduction of calbindin expression by chronic fluoxetine treatment,
      suggesting that dematuration of GCs by fluoxetine does not require adult
      neurogenesis in the DG. CONCLUSIONS: We demonstrated that the 5-HT4 receptor
      plays an important role in fluoxetine-induced adult neurogenesis in the DG in
      addition to GC dematuration, and that these phenomena are closely associated. Our
      results suggest that 5-HT4 receptor-mediated phenotypic changes, including
      dematuration in mature GCs, underlie the neurogenic effect of SSRIs in the DG,
      providing new insight into the cellular mechanisms of the neurogenic actions of
      SSRIs in the hippocampus.

PMID- 25976620
TI  - Quality of life of family caregivers 8 years after a relative's cancer diagnosis:
      follow-up of the National Quality of Life Survey for Caregivers.
AB  - BACKGROUND: The long-term impact of cancer caregiving on the family caregivers'
      quality of life (QOL) is currently not known. This study aimed (a) to
      characterize family caregivers of cancer survivors at 8 years post-diagnosis in
      terms of multidimensional aspects of QOL and (b) to identify demographic and
      early caregiving experience characteristics that may play significant roles in
      predicting the caregivers' longer-term QOL. METHODS: A total of 1087 caregivers
      participated in the 8-year follow-up National Quality of Life Survey for
      Caregivers. Demographics and early caregiving experiences were measured 2 years
      post-diagnosis of their relative's cancer. Multidimensional aspects of QOL were
      assessed, including mental and physical health, psychological adjustment, and
      spirituality at both 2-year and 8-year post-diagnosis. RESULTS: Approximately 90%
      of family caregivers ceased the caregiver role by 8 years. One-fourth of them
      were due to bereavement. Caregivers' demographic and early caregiving
      characteristics were significantly associated with QOL. In addition, being
      bereaved by the 8-year mark predicted poorer mental health and greater
      psychological distress independent of contributions of demographic and early
      caregiving characteristics. CONCLUSIONS: Findings provided the first evidence
      that 8 years after the initial cancer diagnosis in the family, family members who
      became bereaved suffer from poorer mental health and greater psychological
      distress. Findings have theoretical implications for better understanding
      bereavement to cancer and practical implications for developing integrative
      programs to improve QOL among family members in the various phases of
      caregivership.

PMID- 25976621
TI  - Anti-human leukocyte antigen DQ antibodies in renal transplantation: Are we
      underestimating the most frequent donor specific alloantibodies?
AB  - The role of anti-human leukocyte antigens DQ region (HLA-DQ) in transplantation
      is historically less studied than HLA-DR and HLA class I regions, but several
      studies are demonstrating that anti HLA-DQ antibodies are among the most frequent
      anti HLA antibodies that develop after transplantation and can have great
      influence on the developing of humoral rejection and graft loss. In this article
      we review the gene structure and nomenclature of the HLA-DQ region, the role of
      anti HLA-DQ antibodies after and before transplantation and briefly the
      associations of particular HLA-DQ alleles and other diseases. 

PMID- 25976623
TI  - The mRNA and Protein Levels of Tubulin and beta-Actin Are Greatly Reduced in the
      Proximal Duodenum of Mice Relative to the Rest of the Small Intestines.
AB  - To accurately quantify mRNA and protein levels, it is critical to choose
      appropriate internal standards. As the expression of housekeeping genes is
      assumed to remain constant, they are often employed to normalize signals to
      correct for sample-to-sample variations. However, recent studies have documented
      that beta-actin and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression
      levels change in response to various stimuli during proliferation, activation,
      and differentiation. We investigated levels of alpha-, beta-, gamma-tubulin, beta
      actin, and GAPDH vary across the gastrointestinal tract of mice. We found that
      different regions of the small intestines had dramatically different expression
      profiles, as measured by western blot, quantitative Reverse transcription
      polymerase chain reaction (RT-PCR), and immunohistochemical staining. These
      results revealed that the expression levels of tubulins and beta-actin were
      dramatically lower in the proximal duodenum, relative to the rest of the small
      intestines. These varying levels of housekeeping genes may reflect differences in
      the activities of specialized tissues and suggest unique requirements for
      tubulins in these tissue types. We conclude that the use of a single housekeeping
      gene to normalize gene expression in the gastrointestinal tracts of mice may
      introduce errors, as measured differences in gene expression may reflect
      regulation of the internal control rather than the mRNA or protein under
      investigation. 

PMID- 25976622
TI  - Serum miR-181b Is Correlated with Hepatitis B Virus Replication and Disease
      Progression in Chronic Hepatitis B Patients.
AB  - BACKGROUND: Previously, we reported that microRNA-181b (miR-181b) activates
      hepatic stellate cells partly through the phosphatase and tensin homolog deleted
      on chromosome 10 (PTEN)/Akt pathway. AIMS: The main objective of this study was
      to ascertain whether serum miR-181b expression is correlated with that of liver
      hepatitis B virus (HBV) DNA and disease progression in chronic hepatitis B (CHB)
      patients. METHODS: Serum miR-181b and liver HBV DNA levels were quantified in 64
      CHB patients with real-time PCR. Liver fibrosis and necroinflammation were graded
      according to the Ishak scoring system. RESULTS: Serum miR-181b levels were
      evaluated in the CHB group, compared with healthy controls. Expression in
      patients with HBsAg (+) was higher than that in patients with HBsAg (-). Notably,
      serum miR-181b and liver HBV DNA levels were significantly correlated (P < 0.05).
      Serum miR-181 levels were higher in patients with serum HBV DNA > 10(3) IU/ml (P
      = 0.017), histologic activity index (HAI) >8 (P = 0.001) and fibrosis score >4 (P
      < 0.0001). Liver HBV DNA levels were higher in patients with abnormal alanine
      aminotransferase (ALT) values (P = 0.004), serum HBV DNA levels > 10(3) IU/ml (P
      = 0.034) and fibrosis score >4 (P = 0.006). Using multivariate logistic
      regression analysis, serum miR-181b was identified as an independent predictor of
      disease progression (OR 4.172, 95 % CI 1.838-9.473, P = 0.009 for HAI >8; OR
      5.387, 95 % CI 2.067-14.036, P = 0.001 for fibrosis score >4). CONCLUSIONS: Serum
      miR-181b is correlated with liver and serum HBV DNA levels as well as disease
      progression in CHB.

PMID- 25976625
TI  - Erratum to: A Case Series and Literature Review of Merkel Cell Carcinoma
      Metastasizing to Pancreas.

PMID- 25976624
TI  - High Expression of GRP78 Promotes Invasion and Metastases in Patients with
      Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to
      its high frequency of metastasis and invasion. Recent studies have suggested
      glucose-regulated protein 78KD (GRP78) may play important roles in progression
      and development of malignant tumors. However, the mechanisms of invasion and
      metastasis of ESCC in relation to GRP78 still remain obscure. AIM: The aim of
      this study was to investigate the effect of GRP78 on invasion and metastasis of
      ESCC and to explore its potential mechanism. METHODS: GRP78 expression levels in
      ESCC tissues were examined by immunohistochemistry. RT-PCR and western blot were
      used to test the relative expression of GRP78 in non-metastatic and high
      metastatic ESCC cells. In vitro and in vivo studies were both performed to
      investigate the role of GRP78 in invasion and metastasis of ESCC cells. The
      expression of metastasis-related proteins was examined by western blot in GRP78
      depleted cells. RESULTS: The expression of GRP78 is correlated with invasion,
      metastasis and poor prognosis in ESCC patients. GRP78 expression was
      significantly higher in highly metastatic cells compared with ESCC non-metastatic
      cells. In addition, down-regulation of GRP78 significantly inhibited the
      metastatic potential of ESCC cells in both in vitro and in vivo studies. The
      expression of MMP-2 and MMP-9 were down-regulated in GRP78-depleted ESCC cells.
      CONCLUSIONS: The present study demonstrated that GRP78 plays important roles in
      invasion and metastasis of ESCC, indicating that GRP78 might be used as a
      potential prognostic and therapeutic marker in patients with ESCC by modulating
      the expression of MMP-2 and MMP-9.

PMID- 25976626
TI  - Notes on stochastic (bio)-logic gates: computing with allosteric cooperativity.
AB  - Recent experimental breakthroughs have finally allowed to implement in-vitro
      reaction kinetics (the so called enzyme based logic) which code for two-inputs
      logic gates and mimic the stochastic AND (and NAND) as well as the stochastic OR
      (and NOR). This accomplishment, together with the already-known single-input
      gates (performing as YES and NOT), provides a logic base and paves the way to the
      development of powerful biotechnological devices. However, as biochemical systems
      are always affected by the presence of noise (e.g. thermal), standard logic is
      not the correct theoretical reference framework, rather we show that statistical
      mechanics can work for this scope: here we formulate a complete statistical
      mechanical description of the Monod-Wyman-Changeaux allosteric model for both
      single and double ligand systems, with the purpose of exploring their practical
      capabilities to express noisy logical operators and/or perform stochastic logical
      operations. Mixing statistical mechanics with logics, and testing quantitatively
      the resulting findings on the available biochemical data, we successfully revise
      the concept of cooperativity (and anti-cooperativity) for allosteric systems,
      with particular emphasis on its computational capabilities, the related ranges
      and scaling of the involved parameters and its differences with classical
      cooperativity (and anti-cooperativity). 

PMID- 25976627
TI  - Transgalactosylation of lactose for synthesis of galacto-oligosaccharides using
      Kluyveromyces marxianus NCIM 3551.
AB  - Among a number of yeast strains screened for whole cell transgalactosylating
      activity, Kluyveromyces marxianus NCIM 3551 was found to be most suitable
      biocatalyst for production of galacto-oligosaccharides (GOS). Cell
      permeabilization lead to an efficient bioconversion by beta-galactosidase
      resulting in synthesis of GOS. A maximum GOS yield of 36% (w/w) of total sugars
      was achieved and the products consisted of tri- and tetra-galacto
      oligosaccharides. A lactose conversion rate of 80% and productivity of 24g/L/h
      was obtained under the optimum conditions at lactose concentration of 20% (w/v),
      temperature 40 degrees C, pH 6.5 and enzyme units after 3h of reaction time.
      Tetrasaccharides were the main component of the reaction mixture. The products
      were quantitated by HPLC and structurally characterized by mass spectrometry. 

PMID- 25976628
TI  - Simultaneous and selective decarboxylation of L-serine and deamination of L
      phenylalanine in an amino acid mixture--a means of separating amino acids for
      synthesizing biobased chemicals.
AB  - Amino acids (AAs) obtained from the hydrolysis of biomass-derived proteins are
      interesting feedstocks for the chemical industry. They can be prepared from the
      byproduct of biofuel production and agricultural wastes. They are rich in
      functionalities needed in petrochemicals, providing the opportunity to save
      energy, reagents, and process steps. However, their separation is required before
      they can be applied for further applications. Electrodialysis (ED) is a promising
      separation method, but its efficiency needs to be improved when separating AAs
      with similar isoelectric points. Thus, specific conversions are required to form
      product with different charges. Here we studied the enzymatic conversions which
      can be used as a means to aid the ED separation of neutral AAs. A model mixture
      containing L-serine, L-phenylalanine and L-methionine was used. The reactions of
      L-serine decarboxylase and L-phenylalanine ammonia-lyase were employed to
      specifically convert serine and phenylalanine into ethanolamine and trans
      cinnamic acid. At the isoelectric point of methionine (pH 5.74), the charge of
      ethanolamine and trans-cinnamic acid are +1 and -1, therefore facilitating
      potential separation into three different streams by electrodialysis. Here the
      enzyme kinetics, specificity, inhibition and the operational stabilities were
      studied, showing that both enzymes can be applied simultaneously to aid the ED
      separation of neutral AAs.

PMID- 25976629
TI  - Heterologous expression and enzymatic characterization of fructosyltransferase
      from Aspergillus niger in Pichia pastoris.
AB  - In this work, the cDNA encoding fructosyltransferase (FTase) from Aspergillus
      niger YZ59 (CICIM F0901) was obtained and expressed in the methylotrophic yeast
      Pichia pastoris strain GS115. The yield of recombinant FTase in a 5-L fermentor
      reached 1020.0 U/mL after 96 h of induction, which was 1160.4 times higher that
      of native FTase from A. niger YZ59. The specific activity of recombinant FTase
      was 6.8*10(4) U/mg. The optimum temperature and pH of the recombinant FTase were
      55  degrees C and 5.5, respectively. The recombinant FTase was stable below 40 
      degrees C and at pH from 3.0 to 10.0. Using sucrose as the substrate, the Km and
      Vmax values of recombinant FTase were 159.8 g/L and 0.66 g/(L min), respectively.
      The turnover number (kcat) and catalytic efficiency (kcat/Km) of recombinant
      FTase was 1.1*10(4) min(-1) and 68.8 L/(g min), respectively. The recombinant
      FTase was slightly activated by 5mM Ni(2+), Mg(2+), K(+), Fe(3+), or Mn(2+), but
      inhibited by all other metal ions (Na(+), Li(+), Ba(2+), Ca(2+), Zn(2+), and
      Cu(2+)). The highest yield of fructooligosaccharides for purified FTase reached
      approximately 343.3 g/L (w/v). This is the first study reporting the heterologous
      expression of FTases from A. niger in P. pastoris. This study plays an important
      role in the fructooligosaccharide synthesis industry by recombinant FTases.

PMID- 25976630
TI  - Composite outcomes in 2.25-mm drug eluting stents: a systematic review.
AB  - BACKGROUND: Coronary atherosclerosis often involves small-caliber coronaries, yet
      the safety and efficacy of 2.25-mm DES have been poorly defined, with a general
      lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head
      2.25 mm DES studies have been reported. There are several single-arm prospective
      studies, and we aim to systematically review all published specific 2.25-mm data
      to estimate composite DES-specific performance and highlight current knowledge
      gaps. METHODS: We performed a systematic literature search of PubMed, EMBASE, Web
      of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic
      and composite clinical outcomes were compared with descriptive statistics.
      RESULTS: 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum
      chromium EES DES-specific outcomes have been reported. Death at 12 months for
      SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of
      target vessel revascularization at 12 months for SES, PES, EES and platinum
      chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months
      to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was
      0.15 +/- 0.11-mm, 0.28 +/- 0.11-mm, and 0.16 +/- 0.41-mm and mean diameter
      restenosis for SES, PES, and EES were 29.5 +/- 6.2%, 34.7 +/- 4.2%, and 20.9 +/-
      22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0%
      to 2.2% in up to 24-months of follow-up. CONCLUSIONS: This systematic review
      summarizes and tabulates all available specific data on 2.25-mm DES. Based on our
      descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile
      for the treatment of very small coronary lesions.

PMID- 25976631
TI  - Effect of High Fat Diets on Body Mass, Oleylethanolamide Plasma Levels and
      Oxytocin Expression in Growing Rats.
AB  - Obesity prevalence in developed countries has promoted the need to identify the
      mechanisms involved in control of feeding and energy balance. We have tested the
      hypothesis that different fats present in diet composition may contribute in body
      weight gain and body indexes by regulation of oxytocin gene (oxt) expression in
      hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats
      were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO)
      and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an
      increasing trend of OEA plasma levels in HOO group, although no significant
      differences were found. However, body weight gain of LF and HOO were similar and
      significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats
      fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which
      could indicate that oxytocin may be modulated by dietary lipids. 

PMID- 25976632
TI  - Perceptual inference.
AB  - Perceptual inference refers to the ability to infer sensory stimuli from
      predictions that result from internal neural representations built through prior
      experience. Methods of Bayesian statistical inference and decision theory model
      cognition adequately by using error sensing either in guiding action or in
      "generative" models that predict the sensory information. In this framework,
      perception can be seen as a process qualitatively distinct from sensation, a
      process of information evaluation using previously acquired and stored
      representations (memories) that is guided by sensory feedback. The stored
      representations can be utilised as internal models of sensory stimuli enabling
      long term associations, for example in operant conditioning. Evidence for
      perceptual inference is contributed by such phenomena as the cortical co
      localisation of object perception with object memory, the response invariance in
      the responses of some neurons to variations in the stimulus, as well as from
      situations in which perception can be dissociated from sensation. In the context
      of perceptual inference, sensory areas of the cerebral cortex that have been
      facilitated by a priming signal may be regarded as comparators in a closed
      feedback loop, similar to the better known motor reflexes in the sensorimotor
      system. The adult cerebral cortex can be regarded as similar to a servomechanism,
      in using sensory feedback to correct internal models, producing predictions of
      the outside world on the basis of past experience. 

PMID- 25976633
TI  - CACNA1C rs1006737 genotype and bipolar disorder: Focus on intermediate phenotypes
      and cardiovascular comorbidity.
AB  - Recently, multiple genome-wide association studies have identified a genetic
      polymorphism (CACNA1C rs1006737) that appears to confer susceptibility for BD.
      This article aims to summarize the existing literature regarding the impact of
      rs1006737 on functional and structural neuroimaging intermediate phenotypes.
      Twenty eight articles, representing 2486 healthy participants, 369 patients with
      BD and 104 healthy first-degree relatives of patients with BD, are incorporated.
      Multiple studies have demonstrated structural differences, functional differences
      associated with emotion-related and frontal-executive tasks, and/or differences
      in behavioral task performance in risk allele carriers (AA or AG). Results
      comparing participants with BD to health controls are generally less pronounced
      than within-group genetic comparisons. The review concludes with an integration
      of how cardiovascular comorbidity may be a relevant mediator of the observed
      findings, and proposes future directions toward optimized therapeutic use of
      calcium channel blockers in BD. 

PMID- 25976634
TI  - Short- and long-lasting consequences of novelty, deviance and surprise on brain
      and cognition.
AB  - When one encounters a novel stimulus this sets off a cascade of brain responses,
      activating several neuromodulatory systems. As a consequence novelty has a wide
      range of effects on cognition; improving perception and action, increasing
      motivation, eliciting exploratory behavior, and promoting learning. Here, we
      review these benefits and how they may arise in the brain. We propose a framework
      that organizes novelty's effects on brain and cognition into three groups. First,
      novelty can transiently enhance perception. This effect is proposed to be
      mediated by novel stimuli activating the amygdala and enhancing early sensory
      processing. Second, novel stimuli can increase arousal, leading to short-lived
      effects on action in the first hundreds of milliseconds after presentation. We
      argue that these effects are related to deviance, rather than to novelty per se,
      and link them to activation of the locus-coeruleus norepinephrine system. Third,
      spatial novelty may trigger the dopaminergic mesolimbic system, promoting
      dopamine release in the hippocampus, having longer-lasting effects, up to tens of
      minutes, on motivation, reward processing, and learning and memory. 

PMID- 25976635
TI  - Evaluation of Baermann apparatus sedimentation time on recovery of Strongylus
      vulgaris and S. edentatus third stage larvae from equine coprocultures.
AB  - Traditional methods of diagnosing equine Strongylinae infections require
      culturing feces, sedimenting the culture media in Baermann apparatuses,
      collecting the sediment, and morphologically identifying recovered third stage
      larvae. However, this method is plagued by low negative predictive values. This
      study evaluated sedimentation time within the Baermann apparatus by comparing
      larval recovery from the traditionally collected sediment, "sediment 1", and from
      the usually discarded remaining fluid contents, "sediment 2", of the Baermann
      apparatus after 12, 24, and 48 h. A grand total of 147,482 larvae were recovered
      and examined. Sedimentation time did not significantly influence total larval
      recovery. At all three durations, significantly more Cyathostominae and
      Strongylus vulgaris larvae were covered from sediment 1 than from sediment 2.
      However, less than 60% of all recovered Strongylus edentatus were recovered from
      sediment 1. As 95% of S. vulgaris larvae were always recovered from sediment 1,
      the need for collection and examination of the remaining fluid contents of the
      Baermann apparatus is obviated when performing coprocultures for diagnosis of S.
      vulgaris infections, and sedimentation for 12h is adequate. Approximately 70% of
      Cyathostominae were recovered in sediment 1 at all durations, suggesting that 12h
      of sedimentation is adequate, although there is a need for future research to
      evaluate the risk of selection bias at differing sedimentation times among
      individual cyathostomin species. In contrast to S. vulgaris, collecting and
      examining the entire contents of the Baermann apparatus may be necessary when an
      increased diagnostic sensitivity and negative predictive value is desired in
      diagnosing S. edentatus infections as only 38-61% of larvae were recovered from
      sediment 1 portion of the Baermann apparatus. This information will allow
      researchers and practitioners to make more informed decisions in choosing
      appropriate larval recovery techniques, balancing recovery, time, and effort.

PMID- 25976636
TI  - Low T3 syndrome in canine babesiosis associated with increased serum IL-6
      concentration and azotaemia.
AB  - Low triiodothyronine (T3) syndrome, also named euthyroid sick syndrome or non
      thyroidal illness syndrome, has been recognized in canine babesiosis caused by
      Babesia rossi, where it manifested by lowering of the serum thyrotropin (TSH),
      total thyroxin (TT4) and free thyroxin (FT4) concentrations. This syndrome has
      also been observed in critical diseases in humans and animals, and the severity
      of the disease is considered an important factor in lowering of thyroid hormone
      concentrations. Interleukin-6 (IL-6) plays a role in the development of low T3
      syndrome by causing a decrease in deiodinases 1 and 2 activity and increased
      activity of deiodinase 3, enzymes involved in the conversion of thyroxin (T4) to
      T3. The purpose of this study was to compare the concentrations of serum thyroid
      hormones and TSH between healthy dogs and dogs with babesiosis, and to determine
      correlations between serum IL-6 concentration and serum total T3 (TT3), TT4, FT4,
      and TSH concentrations, and the level of azotaemia in dogs with babesiosis. The
      concentrations of IL-6, TT3, TT4, FT4, TSH, urea and creatinine were determined
      in 13 dogs with canine babesiosis caused by Babesia canis and in 10 healthy dogs.
      The results of this study showed decreases in TT3, TT4, FT4, and TSH and
      increases in IL-6, urea and creatinine concentrations in affected dogs in
      comparison to healthy dogs. The concentration of IL-6 was negatively correlated
      with TT3 and TSH concentrations and the TT3 concentration was negatively
      correlated with serum urea and creatinine concentrations. This study showed low
      T3 syndrome in canine babesiosis, which was confirmed by the determination of the
      T3 concentration, and demonstrates that in canine babesiosis the T3 concentration
      is associated with IL-6 concentration. 

PMID- 25976637
TI  - Modeling the distribution of urolithiasis prevalence under projected climate
      change in Iran.
AB  - Although studies support a positive correlation between temperature and stone
      risk, the precise relationship between these factors has not been elucidated. We
      modeled the current distribution of urolithiasis prevalence in Iran using 26
      bioclimatic, climatic and topographic variables based on two multivariate linear
      regression models in geographical information system. The impact of climate
      change on the stone prevalence was predicted under the projections of GFDL-ESM2G,
      CCSM4 and HadGEM2-ES climate models by mid-century (2050). Extraterrestrial
      radiation and isothermality in the first regression model and annual mean
      temperature, precipitation seasonality and isothermality in the second model were
      the significant (P<0.01) predictors of urolithiasis prevalence. Both regression
      models provided good estimates of the stone prevalence (R2>0.9) and determined a
      mean urolithiasis prevalence of 6% (range of 1.5-10.8%) in Iran. The climate
      change under the projections of GFDL-ESM2G, CCSM4 and HadGEM2-ES models can,
      respectively, lead to an average increase of 5.7, 4.3 and 9% in the urolithiasis
      prevalence based on the second regression model by 2050. The highest increase of
      the prevalence will occur in the west, northwest and southwest provinces of the
      country. Predicting the impact of climate change on climate-related diseases can
      be useful for effective preventive measures.

PMID- 25976638
TI  - Matched optical quality comparison of 3-year results of PRK-MMC and phakic IOL
      implantation in the correction of high myopia.
AB  - AIMS: To compare 3-year results of PRK-MMC and phakic intraocular lens (PIOL)
      implantation in patients with >8.0 diopters (D) of myopia. METHODS: This study
      was conducted as a non-randomized clinical trial on 23 eyes treated with PIOL
      (Artiflex; group A) and 23 eyes treated with PRK-MMC (group B). This report
      compares 3-year treatment results in these two groups. RESULTS: At 3 years after
      surgery, uncorrected visual acuity was 0.02+/-0.06 LogMAR in group A and 0.04+/
      0.07 LogMAR in group B (P=0.639). Mean best corrected visual acuity in group A
      (0.004+/-0.02) was better than group B (0.03+/-0.07 LogMAR) (P=0.035). Mean
      manifest refraction spherical equivalent was -0.16+/-0.21 and -0.09+/-0.20D
      (P=0.190), respectively. Mesopic contrast sensitivity (CS) in the spatial
      frequency of three cycle/degree (CS3) significantly decreased in both groups, but
      the reduction was significantly higher in group B (P=0.024). CS6 decreased
      significantly only in group B (P=0.019). Changes in CS12 and CS18 showed no
      significant inter-group difference. In group A, the increase in C6 trefoil
      (0.16+/-0.18 MUm, P=0.003) and reduction in spherical aberration (SA; 0.16+/-0.08
      MUm, P<0.001) were statistically significant. In group B, the reduction in
      vertical coma (P=0.052), and increases in horizontal coma (P=0.044), coma
      (P<0.001), SA (P<0.001), and total higher order aberrations (P<0.001) were
      significant after surgery. CONCLUSION: Based on 3-year results, PIOL implantation
      is a better choice than PRK-MMC for treating patients with >8.0D myopia. However,
      for patients with an inadequate aqueous depth, PRK-MMC can be an acceptable
      treatment option with a potential for decreased quality of vision.

PMID- 25976639
TI  - New antithrombotic agents and the need for updated ophthalmic surgery guidelines.

PMID- 25976640
TI  - Response to 'Patterns of ranibizumab and aflibercept treatment of central retinal
      vein occlusion in routine clinical practice in the U.S.A.'.

PMID- 25976641
TI  - OCT angiography and sequential quantitative analysis of type 2 neovascularization
      after ranibizumab therapy.
AB  - PURPOSE: To study the precise structural aspects of a type 2 neovascular membrane
      in a patient with age-related macular degeneration (AMD) using optical coherence
      tomography (OCT) angiography and perform sequential quantitative analysis of the
      membrane after ranibizumab therapy. PATIENTS AND METHODS: Split-spectrum
      amplitude-decorrelation (SSADA) OCT angiography macular cubes (3 * 3 mm) were
      acquired with a light source centered at 840 nm, a bandwidth of 45 nm, and an A
      scan-rate of 70 000 scans per second. Visible pathologic vessels were outlined
      manually on average intensity projection en face images, and the area of the
      lesion and the vessel density were measured at baseline and follow-up. RESULTS:
      At baseline, the neovascular lesion measured 4.12 mm(2) and the vessel density
      was 19.83 mm(-1). Four weeks after the first, and 2 and 4 weeks after the second
      ranibizumab injection, OCT angiography revealed a progressively smaller vascular
      lesion (2.32, 1.77 and 1.64 mm(2)), and vessel density (10.24, 8.52 and 7.57 mm(
      1)), although the large central trunks of the lesion were unchanged. CONCLUSIONS:
      In this study, an obvious reduction in size and vessel density of the neovascular
      lesion was noted after treatment with ranibizumab using SSADA OCT angiography
      technology. Microvascular components can be delineated with precision, suggesting
      that this technique may be useful for the management of patients with neovascular
      AMD in a clinical setting as well as for future clinical trials.

PMID- 25976642
TI  - Cataract extraction and patient vision-related quality of life: a cohort study.
AB  - AIMS: Cataract surgery is one of the most common surgeries performed, but its
      overuse has been reported. The threshold for cataract surgery has become
      increasingly lenient; therefore, the selection process and surgical need has been
      questioned. The aim of this study was to evaluate the changes associated with
      cataract surgery in patient-reported vision-related quality of life (VR-QoL).
      METHODS: A prospective cohort study was conducted. Consecutive patients referred
      to cataract clinics in an NHS unit in Scotland were identified. Those listed for
      surgery were invited to complete a validated questionnaire (TyPE) to measure VR
      QoL pre- and post-operatively. TyPE has five different domains (near vision,
      distance vision, daytime driving, night-time driving, and glare) and a global
      score of vision. The influence of pre-operative visual acuity (VA) levels,
      vision, and lens status of the fellow eye on changes in VR-QoL were explored.
      RESULTS: A total of 320 listed patients were approached, of whom 36 were
      excluded. Among the 284 enrolled patients, 229 (81%) returned the questionnaire
      after surgery. Results revealed that the mean overall vision improved, as
      reported by patients. Improvements were also seen in all sub-domains of the
      questionnaire. CONCLUSION: The majority of patients appear to have improvement in
      patient-reported VR-QoL, including those with good pre-operative VA and previous
      surgery to the fellow eye. VA thresholds may not capture the effects of the
      quality of life on patients. This information can assist clinicians to make more
      informed decisions when debating over the benefits of listing a patient for
      cataract extraction.

PMID- 25976643
TI  - Patterns of ranibizumab and aflibercept treatment of central retinal vein
      occlusion in routine clinical practice in the U.S.A.

PMID- 25976644
TI  - Web-based information on glaucoma.

PMID- 25976645
TI  - A novel truncation mutation in GJA1 associated with open angle glaucoma and
      microcornea in a large Chinese family.
AB  - PURPOSE: To identify genetic defects in a large family with open angle glaucoma
      (OAG) and microcornea. METHODS: Genomic DNA was prepared from leukocytes of 15
      individuals from three generations of a Chinese family, including seven
      individuals with OAG and microcornea, one with microcornea alone, and seven
      healthy individuals. Whole exome sequencing was performed on genomic DNA of the
      proband. Candidate variants were obtained through multiple steps of
      bioinformatics analysis and validated by Sanger sequencing and segregation
      analysis. RESULTS: Exome sequencing detected a candidate variant in GJA1, a novel
      truncation mutation (c.791_792delAA, p.K264Ifs*43). This mutation was present in
      all seven individuals with OAG and microcornea and the individual with
      microcornea alone, but not in the seven unaffected relatives in the family. It
      was not present in 1394 alleles from 505 unrelated controls without glaucoma and
      192 normal controls. Extraocular signs were not observed in seven out of the
      eight individuals; only one was affected with dental enamel hypoplasia and
      syndactyly. CONCLUSIONS: A novel truncation mutation in GJA1 is associated with
      OAG and microcornea in a Chinese family. This suggests that GJA1 should be
      included as a candidate gene for glaucoma.

PMID- 25976646
TI  - Relationship between socioeconomic and lifestyle factors and cataracts in
      Koreans: the Korea National Health and Nutrition Examination Survey 2008-2011.
AB  - PURPOSE: Cataracts are the leading cause of visual impairment and blindness, and
      therefore early identification and modification of the risk factors for cataracts
      are meaningful. This study aimed to investigate the relationship between
      socioeconomic status (SES) and lifestyle factors, and age-related cataracts in
      South Korea. METHODS: This cross-sectional study was based on data collected in
      the 2008-2011 Korea National Health and Nutrition Examination Survey. A total of
      15 866 subjects, aged >=40 years, were included. SES was defined using household
      income and education level. Sociodemographic, lifestyle, and other associated
      factors were assessed by health interviews and examinations. Cataracts were
      diagnosed via slit-lamp examination using the Lens Opacities Classification
      System III. RESULTS: The prevalence of any cataract was 38.9% in men and 42.3% in
      women (P<0.001). In women, the risk of cataracts increased with decreases in
      household income (P-value for trend=0.016 and 0.041 in any, and cortical
      cataract, respectively) and education level (P-value for trend=0.009, 0.027, and
      0.016 in any, nuclear, and cortical cataract, respectively) after adjusting for
      confounding factors. Current smoking was correlated with nuclear cataracts in men
      (OR 1.21; 95% CI: 1.00, 1.46 in age-adjusted analysis) and cataract surgery in
      women (OR 2.25; 95% CI: 1.00, 5.04 in multivariate-adjusted analysis).
      CONCLUSIONS: Socioeconomic disparities in cataract prevalence were observed in
      women; current smoking increased the risk of nuclear cataracts in men and surgery
      in women. Public health interventions focusing on gender differences are
      warranted to prevent and treat cataracts.

PMID- 25976648
TI  - Radial glia and neural progenitors in the adult zebrafish central nervous system.
AB  - The adult central nervous system (CNS) of the zebrafish, owing to its enrichment
      in constitutive neurogenic niches, is becoming an increasingly used model to
      address fundamental questions pertaining to adult neural stem cell (NSC) biology,
      adult neurogenesis and neuronal repair. Studies conducted in several CNS
      territories (notably the telencephalon, retina, midbrain, cerebellum and spinal
      cord) highlighted the presence, in these niches, of progenitor cells displaying
      NSC-like characters. While pointing to radial glial cells (RG) as major long
      lasting, constitutively active and/or activatable progenitors in most domains,
      these studies also revealed a high heterogeneity in the progenitor subtypes used
      at the top of neurogenic hierarchies, including the persistence of
      neuroepithelial (NE) progenitors in some areas. Likewise, dissecting the
      molecular pathways underlying RG maintenance and recruitment under physiological
      conditions and upon repair in the zebrafish model revealed shared processes but
      also specific cascades triggering or sustaining reparative NSC recruitment.
      Together, the zebrafish adult brain reveals an extensive complexity of adult NSC
      niches, properties and control pathways, which extends existing understanding of
      adult NSC biology and gives access to novel mechanisms of efficient NSC
      maintenance and recruitment in an adult vertebrate brain.

PMID- 25976647
TI  - Sustained supplementation and monitored response with differing carotenoid
      formulations in early age-related macular degeneration.
AB  - PURPOSE: To compare the impact of sustained supplementation using different
      macular carotenoid formulations on macular pigment (MP) and visual function in
      early age-related macular degeneration (AMD). PATIENTS AND METHODS: Sixty-seven
      subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein
      (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso
      zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group
      3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using
      customised heterochromatic flicker photometry and visual function was assessed by
      measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD
      was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11
      step severity scale). RESULTS: At 3 years, a significant increase in MP from
      baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75
      degrees  in Group 1 (P=0.160). Between 24 and 36 months, significant increases in
      MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50
      degrees  in Group 2 (P<0.05), whereas no significant increases were seen in Group
      1 (P>0.05 for all). At 36 months, compared with baseline, the following
      significant improvements (P<0.05) in CS were observed: Group 2-1.2, 6, and 9.6
      cycles per degree (c.p.d.); Group 1-15.15 c.p.d.; and Group 3-6, 9.6, and 15.15
      c.p.d. No significant changes in BCVA, or progression to advanced AMD, were
      observed. CONCLUSION: In early AMD, MP can be augmented with a variety of
      supplements, although the inclusion of MZ may confer benefits in terms of
      panprofile augmentation and in terms of CS enhancement.

PMID- 25976649
TI  - Thymic hyperplasia and chylothorax.

PMID- 25976650
TI  - Abeta peptide secretion is reduced by Radix Polygalae-induced autophagy via
      activation of the AMPK/mTOR pathway.
AB  - Radix Polygalae is a traditional Chinese medicine that has been used as a
      sedative and to improve memory for a number of years. The impact of Radix
      Polygalae in patients with Alzheimer's disease has been investigated. However the
      mechanisms underlying its effects remain unclear. In the current study, the
      toxicity of various doses (100, 40, 20, 10, 5 and 0 MUg/ml) of Radix Polygalae
      was measured in the human neuroblastoma cell line (SH-SY5Y) using an MTT assay.
      Changes in amyloid beta (Abeta) levels in the supernatant of Chinese hamster
      ovary (CHO) cells overexpressing beta-amyloid pro-protein (APP) and BACE1 (CHO
      APP/BACE1), were detected using an ELISA assay. In order to confirm that the
      Abeta reduction was associated with autophagy, the autophagy marker protein,
      light chain 3 (LC3), was measured by western blot analysis and autophagosomes
      were assessed using MDC staining. In addition, the mechanism underlying the
      autophagy induced by Radix Polygalae was analyzed using western blotting to
      measure the protein expression of mammalian target of rapamycin (mTOR), p70s6k,
      Raptor, protein kinase B and adenosine monophosphate-activated protein kinase
      (AMPK), in addition to the phosphorylated forms of these proteins. The results
      demonstrated no significant toxicity of Radix Polygalae in SH-SY5Y cells, at a
      dose of 100 MUg/ml. The secretion of Abeta was markedly reduced following
      treatment with Radix Polygalae, and this reduction occurred in a dose-dependent
      manner. The autophagy levels were shown to be enhanced in the drug treatment
      group, using fluorescence microscopy. In addition, levels of LC3II/LC3I, the
      marker protein of autophagy, were also increased. The results of the current
      study suggest that Radix Polygalae may aid in the elimination of the Abeta
      peptide, via the induction of autophagy, by the AMPK/mTOR signaling pathway.
      These results may provide a basis for further kin vivo investigation.

PMID- 25976651
TI  - Differences in metacognitive regulation in introductory biology students: when
      prompts are not enough.
AB  - Strong metacognition skills are associated with learning outcomes and student
      performance. Metacognition includes metacognitive knowledge-our awareness of our
      thinking-and metacognitive regulation-how we control our thinking to facilitate
      learning. In this study, we targeted metacognitive regulation by guiding students
      through self-evaluation assignments following the first and second exams in a
      large introductory biology course (n = 245). We coded these assignments for
      evidence of three key metacognitive-regulation skills: monitoring, evaluating,
      and planning. We found that nearly all students were willing to take a different
      approach to studying but showed varying abilities to monitor, evaluate, and plan
      their learning strategies. Although many students were able to outline a study
      plan for the second exam that could effectively address issues they identified in
      preparing for the first exam, only half reported that they followed their plans.
      Our data suggest that prompting students to use metacognitive-regulation skills
      is effective for some students, but others need help with metacognitive knowledge
      to execute the learning strategies they select. Using these results, we propose a
      continuum of metacognitive regulation in introductory biology students. By
      refining this model through further study, we aim to more effectively target
      metacognitive development in undergraduate biology students.

PMID- 25976652
TI  - Helping struggling students in introductory biology: a peer-tutoring approach
      that improves performance, perception, and retention.
AB  - The high attrition rate among science, technology, engineering, and mathematics
      (STEM) majors has long been an area of concern for institutions and educational
      researchers. The transition from introductory to advanced courses has been
      identified as a particularly "leaky" point along the STEM pipeline, and students
      who struggle early in an introductory STEM course are predominantly at risk. Peer
      tutoring programs offered to all students in a course have been widely found to
      help STEM students during this critical transition, but hiring a sufficient
      number of tutors may not be an option for some institutions. As an alternative,
      this study examines the viability of an optional peer-tutoring program offered to
      students who are struggling in a large-enrollment, introductory biology course.
      Struggling students who regularly attended peer tutoring increased exam
      performance, expert-like perceptions of biology, and course persistence relative
      to their struggling peers who were not attending the peer-tutoring sessions. The
      results of this study provide information to instructors who want to design
      targeted academic assistance for students who are struggling in introductory
      courses.

PMID- 25976653
TI  - The Faculty Self-Reported Assessment Survey (FRAS): differentiating faculty
      knowledge and experience in assessment.
AB  - Science, technology, engineering, and mathematics education reform efforts have
      called for widespread adoption of evidence-based teaching in which faculty
      members attend to student outcomes through assessment practice. Awareness about
      the importance of assessment has illuminated the need to understand what faculty
      members know and how they engage with assessment knowledge and practice. The
      Faculty Self-Reported Assessment Survey (FRAS) is a new instrument for evaluating
      science faculty assessment knowledge and experience. Instrument validation was
      composed of two distinct studies: an empirical evaluation of the psychometric
      properties of the FRAS and a comparative known-groups validation to explore the
      ability of the FRAS to differentiate levels of faculty assessment experience. The
      FRAS was found to be highly reliable (alpha = 0.96). The dimensionality of the
      instrument enabled distinction of assessment knowledge into categories of program
      design, instrumentation, and validation. In the known-groups validation, the FRAS
      distinguished between faculty groups with differing levels of assessment
      experience. Faculty members with formal assessment experience self-reported
      higher levels of familiarity with assessment terms, higher frequencies of
      assessment activity, increased confidence in conducting assessment, and more
      positive attitudes toward assessment than faculty members who were novices in
      assessment. These results suggest that the FRAS can reliably and validly
      differentiate levels of expertise in faculty knowledge of assessment. 

PMID- 25976654
TI  - The best of both worlds: Building on the COPUS and RTOP observation protocols to
      easily and reliably measure various levels of reformed instructional practice.
AB  - Researchers, university administrators, and faculty members are increasingly
      interested in measuring and describing instructional practices provided in
      science, technology, engineering, and mathematics (STEM) courses at the college
      level. Specifically, there is keen interest in comparing instructional practices
      between courses, monitoring changes over time, and mapping observed practices to
      research-based teaching. While increasingly common observation protocols
      (Reformed Teaching Observation Protocol [RTOP] and Classroom Observation Protocol
      in Undergraduate STEM [COPUS]) at the postsecondary level help achieve some of
      these goals, they also suffer from weaknesses that limit their applicability. In
      this study, we leverage the strengths of these protocols to provide an easy
      method that enables the reliable and valid characterization of instructional
      practices. This method was developed empirically via a cluster analysis using
      observations of 269 individual class periods, corresponding to 73 different
      faculty members, 28 different research-intensive institutions, and various STEM
      disciplines. Ten clusters, called COPUS profiles, emerged from this analysis;
      they represent the most common types of instructional practices enacted in the
      classrooms observed for this study. RTOP scores were used to validate the
      alignment of the 10 COPUS profiles with reformed teaching. Herein, we present a
      detailed description of the cluster analysis method, the COPUS profiles, and the
      distribution of the COPUS profiles across various STEM courses at research
      intensive universities.

PMID- 25976655
TI  - Estrogen promotes the survival of human secretory phase endometrial stromal cells
      via CXCL12/CXCR4 up-regulation-mediated autophagy inhibition.
AB  - STUDY QUESTION: What mechanism is involved in regulating the autophagy of
      endometrial stromal cells (ESCs), and does it participate in the pathogenesis of
      endometriosis? SUMMARY ANSWER: CXCL12 down-regulates secretory phase ESC
      autophagy. WHAT IS KNOWN ALREADY: mTOR (mammalian target of rapamycin), the major
      negative regulator of autophagy, is abnormally increased in endometriotic lesions
      and is involved in the direct regulation of endometrial stromal cell (ESC)
      apoptosis. STUDY DESIGN, SIZE, DURATION: Autophagy was measured by transmission
      electron microscopy and immunofluorescence, and in vitro analysis was used to
      measure estrogen/CXCL12/CXCR4 signaling-mediated ESC autophagy.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 31 controls and 31 women
      with histologically confirmed endometriosis were included. We measured the
      autophagy level of normal and endometriosis-derived endometrium, and its
      relationship to the stage of endometriosis, as well as the potential molecular
      and signaling pathways that mediate the aberrant autophagy in endometriosis. MAIN
      RESULTS AND THE ROLE OF CHANCE: Compared with control secretory phase ESCs, a
      significant reduction of the autophagy grade (as observed in TEM), punctuate LC3B
      staining (as observed in immunofluorescence assays), and autophagy-associated
      protein levels were exhibited in secretory phase eutopic ESCs (P < 0.05) and
      ectopic ESCs (P < 0.05) from women with endometriosis. In addition, the autophagy
      level was strongly negatively correlated with the CXCL12 concentration in ESCs
      (R(2) = -0.9694). However, there was no significant difference in autophagy grade
      or CXCL12 concentration between stage I-II and stage III-IV endometriosis-derived
      ectopic ESCs (P > 0.05). Based on a human autophagy PCR array, CXCL12 and CXCR4,
      which is the CXCL12 receptor, in ESCs were predicted to be molecules that mediate
      the abnormally lower autophagy in endometriosis. Accordingly, after estradiol
      (E2) treatment a marked increase in CXCL12 secretion (1.71-fold, P < 0.01) and
      CXCR4 expression (5.07-fold, P < 0.01) in secretory phase ESCs was observed
      together with decreases in autophagy grade (TEM), punctuate LC3B
      immunofluorescent staining and autophagy-associated protein levels (P < 0.05).
      These changes could be reversed by progesterone (P4) (P < 0.05). The suppression
      of autophagy induced by E2 and recombinant human CXCL12 protein could be
      abrogated by an anti-CXCR4 neutralizing antibody and by a NF-kappaB inhibitor (P
      < 0.05), respectively. In addition, estrogen-stimulated CXCL12 secretion led to a
      low population of S phase cells (P < 0.05), as well as a low level of apoptosis
      (P < 0.05) in secretory phase ESCs. LIMITATIONS, REASONS FOR CAUTION: Further
      studies are needed to examine the mechanism of autophagy on ESC apoptosis. WIDER
      IMPLICATIONS OF THE FINDINGS: Measures to increase in endometrial autophagy might
      be a valid, novel approach to reduce local E2-dependent growth of endometriotic
      tissue. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the
      National Natural Science Foundation of China (NSFC) (81471513, 81471548 and
      81270677), the Training Program for Young Talents of Shanghai Health System
      XYQ2013104, the Program for Zhuoxue of Fudan University, and the Program for
      Creative Talents Education of Key Disciplines of Fudan University. None of the
      authors has any conflict of interest to declare.

PMID- 25976656
TI  - Co-operation between the AKT and ERK signaling pathways may support growth of
      deep endometriosis in a fibrotic microenvironment in vitro.
AB  - STUDY QUESTION: How can deep endometriotic stromal cells proliferate and persist
      in a fibrotic environment? SUMMARY ANSWER: The serine/threonine kinase AKT and
      extracellular regulated kinase (ERK) signaling pathways may co-operate to support
      growth of deep endometriotic lesions by enhancing endometriotic stromal cell
      proliferation and survival in a fibrotic microenvironment in vitro. WHAT IS KNOWN
      ALREADY: Endometriosis, particularly deep infiltrating endometriosis, is
      characterized histologically by dense fibrous tissue that is primarily composed
      of type I collagen. This tissue may cause pelvic pain and infertility, which are
      major clinical issues associated with endometriosis. Proliferation of normal
      fibroblasts is tightly regulated, and fibrillar, polymerized type I collagen
      inhibits normal fibroblast proliferation. However, no studies to date have
      investigated how deep endometriotic stromal cells can proliferate and persist in
      a fibrotic environment. STUDY DESIGN, SIZE, DURATION: Endometrial and/or
      endometriotic tissues from 104 patients (61 with and 43 without endometriosis) of
      reproductive age with normal menstrual cycles were analyzed. A total of 25 nude
      mice received a single injection of endometrial fragments from a total of five
      samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated cell
      proliferation, caspase 3/7 activity, and the AKT and ERK signaling pathways in
      endometrial and endometriotic stromal cells on three-dimensional (3D) polymerized
      collagen matrices in vitro. In addition, to determine whether aberrant activation
      of the AKT and ERK pathways is involved during progression of fibrosis in
      endometriosis in vivo, we evaluated the expression of phosphorylated AKT and
      ERK1/2 in endometriotic implants in a nude mouse model of endometriosis. Finally,
      we evaluated the effects of MK2206 (an AKT inhibitor) and U0126 (a MEK inhibitor)
      on cell proliferation, caspase 3/7 activity, and phosphorylation of AKT and
      ERK1/2 of endometriotic stromal cells on 3D polymerized collagen matrices. MAIN
      RESULTS AND THE ROLE OF CHANCE: Proliferation of endometriotic stromal cells was
      significantly less inhibited than that of endometrial stromal cells (P < 0.05) on
      3D polymerized collagen. Levels of phosphorylated AKT, phosphorylated p70S6K and
      phosphorylated ERK1/2 were significantly higher in endometriotic stromal cells
      than in endometrial stromal cells at 24 h (P < 0.05) and at 72 h (P < 0.05) on 3D
      polymerized collagen. Phosphorylated AKT expression was significantly increased
      on Days 21 and 28 compared with those on Days 3 and 7 (all P < 0.05) in
      endometriotic implants during progression of fibrosis in a nude mouse model of
      endometriosis. Inhibition of AKT or ERK1/2 with MK2206 or U0126, respectively,
      did not significantly increase caspase 3/7 activity in endometriotic stromal
      cells on either two-dimensional or 3D collagen matrices. Western blot analysis
      showed that MK2206 alone decreased levels of phosphorylated AKT; however, it
      increased levels of phosphorylated ERK in endometriotic cells compared with
      vehicle-treated cells (both P < 0.05). In addition, U0126 treatment decreased
      levels of phosphorylated ERK; however, it resulted in increased levels of
      phosphorylated AKT in endometriotic stromal cells compared with vehicle-treated
      cells (both P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Endometriosis involves a
      number of processes, such as invasion, metastasis, angiogenesis, and apoptosis
      resistance, and a variety of signaling pathways may be involved in promoting
      development and progression of the disease. In addition, further animal
      experiments are required to determine whether the AKT and ERK signaling pathways
      co-operate to support growth of endometriotic lesions in a fibrotic
      microenvironment in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Co-targeting the
      AKT and ERK pathways may be an effective therapeutic strategy for endometriosis
      treatment. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by
      Karl Storz Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are
      declared.

PMID- 25976657
TI  - CDC analysis of ICSI/autism: association is not causation.

PMID- 25976658
TI  - Reply: CDC analysis of ICSI/autism: association is not causation.

PMID- 25976659
TI  - Which blastocysts should be considered for genetic screening?

PMID- 25976660
TI  - Reply: Which blastocysts should be considered for genetic screening?

PMID- 25976661
TI  - The natural phytochemical dehydroabietic acid is an anti-aging reagent that
      mediates the direct activation of SIRT1.
AB  - Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid of
      confers, such as pinus species (P. densiflora, P. sylvestris) and grand fir
      (Abies grandis), and it induces various biological actions including
      antimicrobial, antiulcer, and cardiovascular activities. The cellular targets
      that mediate these actions are largely unknown yet. In this report, we suggest
      that DAA is an anti-aging reagent. DAA has lifespan extension effects in
      Caenorhabditis elegans, prevents lipofuscin accumulation, and prevents collagen
      secretion in human dermal fibroblasts. We found that these anti-aging effects are
      primarily mediated by SIRT1 activation. Lifespan extension effects by DAA were
      ameliorated in sir-2.1 mutants and SIRT1 protein expression was increased,
      resulting in the deacetylation of SIRT1 target protein PGC-1alpha. Moreover, DAA
      binds directly to the SIRT1 protein independent of the SIRT1 substrate NAD(+)
      levels. Through a molecular docking study, we also propose a binding model for
      DAA-SIRT1. Taken together, our results demonstrate that the anti-aging effects
      are the first identified biological property of DAA and that the direct
      activation of SIRT1 enzymatic activity suggests the potential use of this natural
      diterpene, or related compounds, in age-related diseases or as a preventive
      reagent against the aging process.

PMID- 25976662
TI  - Exendin-4 protects rat islets against loss of viability and function induced by
      brain death.
AB  - Islet quality loss after isolation from brain-dead donors still hinders the
      implementation of human islet transplantation for treatment of type 1 diabetes.
      In this scenario, systemic inflammation elicited by donor brain death (BD) is
      among the main factors influencing islet viability and functional impairment.
      Exendin-4 is largely recognized to promote anti-inflammatory and cytoprotective
      effects on beta-cells. Therefore, we hypothesized that administration of exendin
      4 to brain-dead donors might improve islet survival and insulin secretory
      capabilities. Here, using a rat model of BD, we demonstrate that exendin-4
      administration to the brain-dead donors increases both islet viability and
      glucose-stimulated insulin secretion. In this model, exendin-4 treatment produced
      a significant decrease in interleukin-1beta expression in the pancreas.
      Furthermore, exendin-4 treatment increased the expression of superoxide dismutase
      2 and prevented BD-induced elevation in uncoupling protein-2 expression. Such
      observations were accompanied by a reduction in gene expression of two genes
      often associated with endoplasmic reticulum (ER) stress response in freshly
      isolated islets from treated animals, C/EBP homologous protein and immunoglobulin
      heavy-chain binding protein. As ER stress response has been shown to be triggered
      by and to participate in cytokine-induced beta-cell death, we suggest that
      exendin-4 might exert its beneficial effects through alleviation of pancreatic
      inflammation and oxidative stress, which in turn could prevent islet ER stress
      and beta-cell death. Our findings might unveil a novel strategy to preserve islet
      quality from brain-dead donors. After testing in the human pancreatic islet
      transplantation setting, this approach might sum to the ongoing effort to achieve
      consistent and successful single-donor islet transplantation. 

PMID- 25976663
TI  - Milk lipid composition is modified by perinatal exposure to bisphenol A.
AB  - To evaluate whether bisphenol A (BPA) modifies the synthesis, composition and/or
      profile of fatty acids (FAs) in the mammary glands of perinatally exposed
      animals, pregnant rats were orally exposed to 0, 0.6 or 52 ug BPA/kg/day from
      gestation day (GD) 9 until weaning. F1 females were bred, and on GD21, lactation
      day 2 (LD2) and LD10, mammary glands were obtained. On LD10, milk samples were
      collected, and FA profiles and lipid compositions were established. On GD21 and
      LD2, BPA exposure delayed mammary alveolar maturation and modified the synthesis
      of milk fat globules. On LD10, mammary gland histo-architecture was restored;
      however, the milk of BPA-exposed F1 dams had a FA profile and lipid concentration
      different from those of the control milk. Furthermore, the body weight gain of
      BPA52 F2 pups was increased compared with control animals. Thus, perinatal
      exposure to BPA modifies milk quality, compromising the normal growth of
      offspring. 

PMID- 25976665
TI  - Effects of delayed motherhood on hippocampal gene expression in offspring rats.
AB  - While many studies have examined the pregnancy and health-related outcomes of
      delayed motherhood for women, less is known concerning the potential consequences
      for their children. This study aims to investigate the effect of delayed
      motherhood on the hippocampus at the whole genome level. Sprague-Dawley rat
      females, either at the age of 3 or 12 months, were individually housed with a
      randomly selected 3-month-old male. The rat whole genome expression chips were
      used to detect gene expression differences in the hippocampus of newborn rats.
      The gene expression profile was studied through gene ontology and signal pathway
      analyses. qRT-PCR was used to determine the mRNA expression of solute carrier
      family 2 (SLC2A1) and S-phase kinase-associated protein 2 (SKP2). Western blot
      was used to detect the protein expression of SKP2. Compared to the control group,
      1291 differentially expressed genes were detected, including 635 up-regulated
      genes and 656 down-regulated genes. These differential expressed genes were
      involved in 110 significant biological process and nine significant signaling
      pathways, in which the pathway in cancer is the most changed pathway. For SKP2
      (up-regulated) and SLC2A1 (up-regulated) genes which were relevant to the pathway
      in cancer, qRT-PCR results were consistent with gene chip assay results. The
      upregulation of SKP2 was also demonstrated at protein level. In conclusion,
      delayed motherhood led to unique patterns of hippocampal gene expression in
      offspring and the newly identified genes afford a quantitative view of the
      changes which enable deeper insights into the molecular basis underlying the role
      of delayed motherhood.

PMID- 25976666
TI  - Ligand specific variation in cardiac response to stimulation of peroxisome
      proliferator-activated receptor-alpha in spontaneously hypertensive rat.
AB  - Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac
      failure. Reduction of LVH has beneficial effects on the heart. LVH is associated
      with shift in energy substrate preference from fatty acid to glucose, mediated by
      down regulation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha).
      As long-term dependence on glucose can promote adverse cardiac remodeling, it was
      hypothesized that, prevention of metabolic shift by averting down regulation of
      PPAR-alpha can reduce cardiac remodeling in spontaneously hypertensive rat (SHR).
      Cardiac response to stimulation of PPAR-alpha presumably depends on the type of
      ligand used. Therefore, the study was carried out in SHR, using two different
      PPAR-alpha ligands. SHR were treated with either fenofibrate (100 mg/kg/day) or
      medium-chain triglyceride (MCT) Tricaprylin (5% of diet) for 4 months. Expression
      of PPAR-alpha and medium-chain acylCoA dehydrogenase served as markers, for
      stimulation of PPAR-alpha. Both ligands stimulated PPAR-alpha. Decrease of blood
      pressure was observed only with fenofibrate. LVH was assessed from heart
      weight/body weight ratio, histology and brain natriuretic peptide expression. As
      oxidative stress is linked with hypertrophy, serum and cardiac malondialdehyde
      and cardiac 3-nitrotyrosine levels were determined. Compared to untreated SHR,
      LVH and oxidative stress were lower on supplementation with MCT, but higher on
      treatment with fenofibrate. The observations indicate that reduction of blood
      pressure is not essentially accompanied by reduction of LVH, and that,
      progressive cardiac remodeling can be prevented with decrease in oxidative
      stress. Contrary to the notion that reactivation of PPAR-alpha is detrimental;
      the study substantiates that cardiac response to stimulation of PPAR-alpha is
      ligand specific.

PMID- 25976664
TI  - PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis.
AB  - Vascular development and maintenance of proper vascular function through various
      regulatory mechanisms are critical to our wellbeing. Delineation of the
      regulatory processes involved in development of the vascular system and its
      function is one of the most important topics in human physiology and
      pathophysiology. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a
      cell adhesion molecule with proangiogenic and proinflammatory activity, has been
      the subject of numerous studies. In the present review, we look at the important
      roles that PECAM-1 and its isoforms play during angiogenesis, and its molecular
      mechanisms of action in the endothelium. In the endothelium, PECAM-1 not only
      plays a role as an adhesion molecule but also participates in intracellular
      signalling pathways which have an impact on various cell adhesive mechanisms and
      endothelial nitric oxide synthase (eNOS) expression and activity. In addition,
      recent studies from our laboratory have revealed an important relationship
      between PECAM-1 and endoglin expression. Endoglin is an essential molecule during
      angiogenesis, vascular development and integrity, and its expression and activity
      are compromised in the absence of PECAM-1. In the present review we discuss the
      roles that PECAM-1 isoforms may play in modulation of endothelial cell adhesive
      mechanisms, eNOS and endoglin expression and activity, and angiogenesis. 

PMID- 25976667
TI  - ERK5 signalling pathway is essential for fluid shear stress-induced COX-2 gene
      expression in MC3T3-E1 osteoblast.
AB  - Bone cells respond to various mechanical stimuli including fluid shear stress
      (FSS) in vitro. Induction of cyclooxygenase-2 (COX-2) is thought to be important
      for the anabolic effects of mechanical loading. Recently, extracellular-signal
      regulated kinase 5 (ERK5) has been found to be involved in multiple cellular
      processes. However, the relationship between ERK5 and the induction of COX-2 is
      still unknown. Here, we investigated the potential involvement of ERK5 in the
      response of pre-osteoblastic MC3T3-E1 cells upon FSS. MC3T3-E1 cells were
      subjected to 12 dyn/cm(2) FSS. Then, we established a ERK5 small interfering RNA
      (siRNA) transfected cell line using the MC3T3-E1 cells. After the successful
      transfection confirmed by real-time reverse transcription-polymerase chain
      reaction and Western blotting, the expression of COX-2, cAMP response element
      binding protein (CREB), and nuclear factor kappa B cells (NF-kappaB) were assayed
      for downstream effectors of activated ERK5 under FSS by Western blotting. Our
      results showed that FSS could stimulate COX-2 activity, and induce the
      phosphorylation of ERK5, CREB, and NF-kappaB. When the MC3T3-E1 cells were
      transfected using siRNA before exposure to FSS, COX-2 activity was suppressed,
      and the phosphorylation of CREB and NF-kappaB was significantly downregulated. In
      summary, we demonstrated that ERK5 pathway is essential in the induction of COX-2
      gene. 

PMID- 25976668
TI  - Arginase I expression is upregulated by dietary restriction in the liver of mice
      as a function of age.
AB  - Arginase is a cytosolic enzyme that catalyzes the hydrolysis of L-arginine to L
      ornithine and urea. This reaction comprises the final step of the urea cycle,
      which provides the principal route for the disposal of nitrogenous waste from
      protein catabolism. The present study investigates the normal endogenous activity
      and expression level of arginase I as a function of age in the liver of 2-, 6-,
      and 18-month-old mice. The effect of dietary restriction (DR) on the expression
      of arginase I was also investigated in two age groups of mice, 2- and 18-month
      old. Arginase I activity was assessed spectrophotometrically, and the level of
      arginase I protein was further confirmed by Western blotting analyses. Arginase I
      mRNA level was measured using real-time PCR. Our results show that the arginase I
      activity (U/mg protein) and protein level in liver was higher in 2-month-old mice
      and decreased gradually with age. In contrast, arginase I mRNA was observed to be
      higher in the older mice as compared to the younger mice. DR was seen to
      upregulate the arginase I activity and expression in both 2- and 18-month-old
      mice. The findings concluded that arginase I is down-regulated with the
      advancement of age in the liver of mice and is upregulated by DR. This suggests
      that DR plays an important role in maintaining related metabolic processes as a
      function of age in mice. 

PMID- 25976670
TI  - Let7a involves in neural stem cell differentiation relating with TLX level.
AB  - Neural stem cells (NSCs) have the potential for differentiation into neurons
      known as a groundbreaking therapeutic solution for central nervous system (CNS)
      diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have
      focused on the study on microRNA's role in CNS. Some micro RNAs have been
      reported significant functions in NSC self-renewal and differentiation through
      the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a)
      has known as the regulator of diverse cellular mechanisms including cell
      differentiation and proliferation. In present study, we investigated whether
      Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which
      is an essential regulator of NSC self-renewal, proliferation and differentiation.
      We performed the following experiments: western blot analysis, TaqMan assay, RT
      PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed
      that let7a play important roles in controlling NSC fate determination. Thus,
      manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency
      of NSC's neuronal differentiation for CNS disorders. 

PMID- 25976669
TI  - Hierarchical decomposition of dynamically evolving regulatory networks.
AB  - BACKGROUND: Gene regulatory networks describe the interplay between genes and
      their products. These networks control almost every biological activity in the
      cell through interactions. The hierarchy of genes in these networks as defined by
      their interactions gives important insights into how these functions are
      governed. Accurately determining the hierarchy of genes is however a
      computationally difficult problem. This problem is further complicated by the
      fact that an intrinsic characteristic of regulatory networks is that the wiring
      of interactions can change over time. Determining how the hierarchy in the gene
      regulatory networks changes with dynamically evolving network topology remains to
      be an unsolved challenge. RESULTS: In this study, we develop a new method, named
      D-HIDEN (Dynamic-HIerarchical DEcomposition of Networks) to find the hierarchy of
      the genes in dynamically evolving gene regulatory network topologies. Unlike
      earlier methods, which recompute the hierarchy from scratch when the network
      topology changes, our method adapts the hierarchy based on the wiring of the
      interactions only for the nodes which have the potential to move in the
      hierarchy. CONCLUSIONS: We compare D-HIDEN to five currently available
      hierarchical decomposition methods on synthetic and real gene regulatory
      networks. Our experiments demonstrate that D-HIDEN significantly outperforms
      existing methods in running time, accuracy, or both. Furthermore, our method is
      robust against dynamic changes in hierarchy. Our experiments on human gene
      regulatory networks suggest that our method may be used to reconstruct hierarchy
      in gene regulatory networks.

PMID- 25976671
TI  - The endoplasmic reticulum-localized protein TBL2 interacts with the 60S ribosomal
      subunit.
AB  - Transducin (beta)-like 2 (TBL2) is a poorly characterized protein comprising the
      N-terminal transmembrane region and the C-terminal WD40 domain. We previously
      showed that TBL2 is an endoplasmic reticulum (ER)-localized protein that
      interacts with PKR-like ER-resident kinase (PERK), and under ER stress, it
      mediates protein expression of activating transcription factor 4 (ATF4). However,
      further molecular characterization of TBL2 is useful to better understand the
      function of this molecule. Here, we show that TBL2 associates with the eukaryotic
      60S ribosomal subunit but not with the 40S subunit. The association of TBL2 with
      the 60S subunit was ER stress independent while the TBL2-PERK interaction
      occurred upon ER stress. Immunoprecipitation analysis using TBL2 deletion mutants
      revealed that the WD40 domain was essential for the 60S subunit association.
      These results could provide an important clue to understanding how TBL2 is
      involved in the expression of specific proteins under ER stress conditions. 

PMID- 25976672
TI  - Mig-6 regulates endometrial genes involved in cell cycle and progesterone
      signaling.
AB  - Mitogen inducible gene 6 (Mig-6) is an important mediator of progesterone (P4)
      signaling to inhibit estrogen (E2) signaling in the uterus. Ablation of Mig-6 in
      the murine uterus leads to the development of endometrial hyperplasia and E2
      induced endometrial cancer. To identify the molecular pathways regulated by Mig
      6, we performed microarray analysis on the uterus of ovariectomized Mig-6(f/f)
      and PGR(cre/+)Mig-6(f/f) (Mig-6(d/d)) mice treated with vehicle or P4 for 6 h.
      The results revealed that 772 transcripts were significantly regulated in the Mig
      6(d/d) uterus treated with vehicle as compared with Mig-6(f/f) mice. The pathway
      analysis showed that Mig-6 suppressed the expression of gene-related cell cycle
      regulation in the absence of ovarian steroid hormone. The epithelium of Mig
      6(d/d) mice showed a significant increase in the number of proliferative cells
      compared to Mig-6(f/f) mice. This microarray analysis also revealed that 324
      genes are regulated by P4 as well as Mig-6. Cited2, the developmentally important
      transcription factor, was identified as being regulated by the P4-Mig-6 axis. To
      determine the role of Cited2 in the uterus, we used the mice with Cited2 that
      were conditionally ablated in progesterone receptor-positive cells
      (PGR(cre/+)Cited2(f/f); Cited2(d/d)). Ablation of Cited2 in the uterus resulted
      in a significant reduction in the ability of the uterus to undergo a hormonally
      induced decidual reaction. Identification and analysis of these responsive genes
      will help define the role of P4 as well as Mig-6 in regulating uterine biology. 

PMID- 25976673
TI  - Understanding V(D)J recombination initiator RAG1 gene using molecular
      phylogenetic and genetic variant analyses and upgrading missense and non-coding
      variants of clinical importance.
AB  - The recombination-activating genes (RAGs) encode for V(D)J recombinases
      responsible for rearrangements of antigen-receptor genes during T and B cell
      development, and RAG expression is known to correlate strictly with the process
      of rearrangement. There have been several studies of RAG1 illustrating
      biochemical, physiological and immunological properties. Hitherto, there are
      limited studies on RAG1 focusing molecular phylogenetic analyses, evolutionary
      traits, and genetic variants in human populations. Hence, there is a need of a
      comprehensive study on this topic. In the current report, we have shed light into
      insights of evolutionary traits and genetic variants of human RAG1 gene using
      1092 genomes from human populations. Syntenic analyses revealed that two RAG
      genes are physically linked and conserved on the same locus in head-to-head
      orientation from sea urchin to human for about 550 MY. Spliceosomal introns have
      been in invaded in fishes and sea urchin, whereas gene structures of RAG1 gene
      from tetrapods remained single exon architecture. We compiled 751 genetic
      variants in human RAG1 gene using 1092 human genomes; where major stockholders of
      variant classes are 79% single nucleotide polymorphisms (SNPs), 12.2% somatic
      single nucleotide variants (somatic SNVs) and 6.8% deletion. Out of 267 missense
      variants, 140 are deleterious mutations. We identified 284 non-coding variants
      with 94% regulatory in nature. 

PMID- 25976674
TI  - The anti-hypertensive drug reserpine induces neuronal cell death through
      inhibition of autophagic flux.
AB  - Reserpine is a well-known medicine for the treatment of hypertension and
      schizophrenia, but its administration can induce Parkinson's disease (PD)-like
      symptoms in humans and animals. Reserpine inhibits the vesicular transporter of
      monoamines and depletes the brain of monoamines such as dopamine. However, the
      cellular function of reserpine is not fully understood. In this report, we
      present one possible mechanism by which reserpine may contribute to PD-like
      symptoms. Reserpine treatment induced the formation of enlarged autophagosomes by
      inhibiting the autophagic flux and led to accumulation of p62, an autophagy
      adapter molecule. In particular, reserpine treatment increased the level of alpha
      synuclein protein and led to accumulation of alpha-synuclein in autophagosomes.
      Treatment with rapamycin enhanced the effect of reserpine by further increasing
      the level of alpha-synuclein and neuronal cell death. Drosophila raised on media
      containing reserpine showed loss of dopaminergic neurons. Furthermore,
      cotreatment with reserpine and rapamycin aggravated the loss of dopaminergic
      neurons. Our results suggest that reserpine contributes to the loss of
      dopaminergic neurons by interfering with autophagic flux. 

PMID- 25976675
TI  - Alteration of cell cycle progression by Sindbis virus infection.
AB  - We examined the impact of Sindbis virus (SINV) infection on cell cycle
      progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero.
      Cell cycle analyses showed that SINV infection is able to alter the cell cycle
      progression in both HeLa and Vero cells, but differently, especially during the
      early stage of infection. SINV infection affected the expression of several cell
      cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells
      and caused HeLa cells to accumulate in S phase during the early stage of
      infection. Monitoring SINV replication in HeLa and Vero cells expressing cell
      cycle indicators revealed that SINV which infected HeLa cells during G1 phase
      preferred to proliferate during S/G2 phase, and the average time interval for
      viral replication was significantly shorter in both HeLa and Vero cells infected
      during G1 phase than in cells infected during S/G2 phase. 

PMID- 25976676
TI  - Effect in dedicator of cytokinesis 6 (DOCK6) on steroid production in theca cells
      of follicular cysts.
AB  - Ovarian follicular cysts are one of the most common causes of reproductive
      failure in mammals. A comparative gene expression approach may aid in elucidating
      the causes of ovarian cyst disease. In the present study, the differential
      display technique was used to identify mRNA sequences that accumulate
      preferentially in theca cells of bovine cystic follicles. Dedicator of
      cytokinesis 6 (Dock6) expression was observed in the theca cells of cystic
      follicles. Small interfering RNA (siRNA) knockdown of Dock6 increased
      progesterone (P4) production and StAR expression in theca cells of high-estrogen
      follicular cysts, but did not affect androstenedione (A4) production. We propose
      that Dock6 may be a marker associated with the development of follicular cysts.
      Additionally, Dock6 may be involved in the development of cystic follicles by
      suppressing P4 production rather than increasing A4 production in theca cells. 

PMID- 25976677
TI  - Dysregulation of long non-coding RNAs in mouse models of localization-related
      epilepsy.
AB  - Genome-wide profiling has revealed that eukaryotic genomes are transcribed into
      numerous non-coding RNAs. In particular, long non-coding RNAs (lncRNAs) have been
      implicated in various human diseases due to their biochemical and functional
      diversity. Epileptic disorders have been characterized by dysregulation of
      epigenetic regulatory mechanisms, and recent studies have identified several
      lncRNAs involved in neural development and network function. However,
      comprehensive profiling of lncRNAs implicated in chronic epilepsy has been
      lacking. In this study, microarray analysis was performed to obtain the
      expression profile of lncRNAs dysregulated in pilocarpine and kainate models, two
      models of temporal lobe epilepsy commonly used for studying epileptic mechanisms.
      Total of 4622 lncRNAs were analyzed: 384 lncRNAs were significantly dysregulated
      in pilocarpine model, and 279 lncRNAs were significantly dysregulated in kainate
      model compared with control mice (>=3.0-fold, p < 0.05). Among these, 54 and 14
      lncRNAs, respectively, had adjacent protein-coding genes whose expressions were
      also significantly dysregulated (>=2.0-fold, p < 0.05). Majority of these pairs
      of lncRNAs and adjacent genes shared the same direction of dysregulation. For the
      selected adjacent gene-lncRNA pairs, significant Gene Ontology terms were
      embryonic appendage morphogenesis and neuron differentiation. This was the first
      study to comprehensively identify dysregulated lncRNAs in two different models of
      chronic epilepsy and will likely provide a novel insight into developing lncRNA
      therapeutics. 

PMID- 25976678
TI  - Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and
      Epigenetic Regulation in Breast Cancer Cells.
AB  - Cambogin is a polycyclic polyprenylated acylphoroglucinol (PPAP) from the
      Garcinia genus, which has been used traditionally for cancer treatment across
      Southeastern Asia. In this study, we found that cambogin inhibited breast cancer
      cell proliferation and induced cell apoptosis in vitro. Cambogin induced the
      activation of the caspase-independent mitochondrial apoptotic pathway, as
      indicated by an increase in the ratio of Bax/Bcl-2 and the nuclear translocation
      of apoptosis inducing factor (AIF). Two-dimensional gel electrophoresis and mass
      spectrometry revealed that the expression of proteins involving in the radical
      oxygen species (ROS) pathway was among the most affected upon cambogin treatment.
      Cambogin enhanced cellular ROS production, and induced the activation of the ASK1
      MKK4/MKK7-JNK/SAPK signaling pathway. Pretreatment with ROS scavenger N
      acetylcysteine (NAC), an antioxidant, or the JNK inhibitor SP600125 was able to
      restore cell viability in the presence of cambogin. Importantly, cambogin
      treatment led to the activation of activating transcription factor-2 (ATF-2) and
      the trimethylation of histone H3K9 in the activator protein 1 (AP-1) binding
      region of the Bcl-2 gene promoter. Finally, cambogin exhibited a potential
      antitumor effect in MCF-7 breast cancer xenografts without apparent toxicity.
      Taken in conjunction, the present study indicates that cambogin can induce breast
      adenocarcinoma cell apoptosis and therefore represents therapeutic potential for
      cancer treatment.

PMID- 25976680
TI  - Calumenin and fibulin-1 on tumor metastasis: Implications for pharmacology.
AB  - Tumor metastasis is a key cause of cancer mortality, and inhibiting migration of
      cancer cells is one of the major directions of anti-metastatic drug development.
      Calumenin and fibulin-1 are two extracellular proteins that synergistically
      inhibit cell migration and tumor metastasis, and could potentially be served as
      targets for pharmacological research of anti-metastatic drugs. This review
      briefly introduces the multi-function of these two proteins, and discusses the
      mechanism of how they regulate cell migration and tumor metastasis. 

PMID- 25976681
TI  - Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal
      function and after unilateral nephrectomy.
AB  - A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and
      zoledronate (ZOL), but interpretation of these study results was limited because
      of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The
      present study investigated the nephrotoxicity of ibandronate and zoledronate in a
      1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in
      rats with normal and with mildly to moderately impaired renal function. We
      compared rats with normal renal function (SHAM) and with impaired renal function
      after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg,
      zoledronate 1mg/kg or placebo once (1*) or nine (9*) times. Renal function and
      markers of tubular toxicity were measured over a 27 week period. After last
      bisphosphonate treatment the rats were sacrificed and kidneys examined
      histologically. All bisphosphonate treated animals showed a significant tubular
      toxicity, which was temporary except in the ZOL-UNX-9*-group. Also the renal
      function was only transiently reduced except in the ZOL-UNX-9*-group.
      Histologically, bisphosphonate treatment led to cortical tubuloepithelial
      degeneration/necrosis and medullary tubuloepithelial swelling which were slightly
      more pronounced in ibandronate treated animals, when compared to zoledronate
      treated animals, especially with impaired renal function. In contrast to the
      previous study we found a similar nephrotoxicity of ibandronate and zoledronate
      in rats with normal renal function. In rats with impaired renal function the peak
      of toxicity had not even been fully reached until end of experiment in the
      zoledronate treated animals. The peak of toxicity seems to be more severe and
      delayed in rats with impaired renal function compared with rats with normal renal
      function. 

PMID- 25976679
TI  - Aromatase Inhibitor-Mediated Downregulation of INrf2 (Keap1) Leads to Increased
      Nrf2 and Resistance in Breast Cancer.
AB  - Aromatase inhibitors are effective drugs that reduce or eliminate hormone
      sensitive breast cancer. However, despite their efficacy, resistance to these
      drugs can occur in some patients. The INrf2 (Keap1):Nrf2 complex serves as a
      sensor of drug/radiation-induced oxidative/electrophilic stress. INrf2
      constitutively suppresses Nrf2 by functioning as an adapter protein for the
      Cul3/Rbx1-mediated ubiquitination/degradation of Nrf2. Upon stress, Nrf2
      dissociates from INrf2, is stabilized, translocates to the nucleus, and
      coordinately induces a battery of cytoprotective gene expression. Current studies
      investigated the role of Nrf2 in aromatase inhibitor resistance. RT-PCR and
      immunoblot assays showed that aromatase inhibitor-resistant breast cancer LTLTCa
      and AnaR cells express lower INrf2 and higher Nrf2 protein levels, as compared
      with drug-sensitive MCF-7Ca and AC1 cells, respectively. The increase in Nrf2 was
      due to lower ubiquitination/degradation of Nrf2 in aromatase inhibitor-resistant
      cells. Higher Nrf2-mediated levels of biotransformation enzymes, drug
      transporters, and antiapoptotic proteins contributed to reduced efficacy of drugs
      and aversion to apoptosis that led to drug resistance. shRNA inhibition of Nrf2
      in LTLTCa (LTLTCa-Nrf2KD) cells reduced resistance and sensitized cells to
      aromatase inhibitor exemestane. Interestingly, LTLTCa-Nrf2KD cells also showed
      reduced levels of aldehyde dehydrogenase, a marker of tumor-initiating cells and
      significantly decreased mammosphere formation, as compared with LTLTCa-Vector
      control cells. The results together suggest that persistent aromatase inhibitor
      treatment downregulated INrf2 leading to higher expression of Nrf2 and Nrf2
      regulated cytoprotective proteins that resulted in increased aromatase inhibitor
      drug resistance. These findings provide a rationale for the development of Nrf2
      inhibitors to overcome resistance and increase efficacy of aromatase inhibitors.

PMID- 25976682
TI  - Pathogenicity of individual rhinovirus species during exacerbations of cystic
      fibrosis.

PMID- 25976683
TI  - Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic
      review.
AB  - As idiopathic pulmonary fibrosis emerges as an important public health problem,
      there is a need to coordinate data on incidence and mortality globally. This
      study aims to systematically assess all available studies to investigate the
      global burden of disease.Medline and Embase databases were searched
      systematically for all population-based studies of incidence or mortality of
      idiopathic pulmonary fibrosis. Clinical case series and prevalence studies were
      excluded. The search was supplemented using the Google search engine, hand
      searching of references and conference abstracts. Data were extracted
      independently by two authors using a pre-specified proforma, with assessment of
      methodological quality.34 studies were identified, providing data from 21
      countries from 1968-2012. 28 studies reported incidence data and eight reported
      mortality data. In studies from the year 2000 onwards, we estimated a
      conservative incidence range of 3-9 cases per 100 000 per year for Europe and
      North America. Incidence was lower in East Asia and South America. The majority
      of studies showed an increase in incidence over time.The incidence of idiopathic
      pulmonary fibrosis is increasing worldwide and rates are coming together across
      countries. Current data suggest incidence is similar to that of conditions such
      as stomach, liver, testicular and cervical cancers. 

PMID- 25976684
TI  - Successful treatment of antineutrophil cytoplasmic antibody-associated
      bronchiectasis with immunosuppressive therapy.

PMID- 25976685
TI  - Sputum induction with inhaled mannitol in children.

PMID- 25976686
TI  - Staging of lung cancer: the role of noninvasive, minimally invasive and invasive
      techniques.
AB  - Accurate staging and restaging of primary tumour and mediastinal nodes in
      patients with lung cancer is of significant importance. For primary tumours,
      computed tomography (CT) scans of the chest are recommended. Positron emission
      tomography (PET) imaging should be used in patients with curative intent
      treatment to evaluate metastatic disease. Diagnosis of the primary tumour should
      be performed using bronchoscopy or CT-guided transthoracic needle aspiration. In
      patients with enlarged mediastinal nodes and no distant metastasis, invasive
      staging of the mediastinum is required. For suspicious N2 or N3 disease,
      endoscopic needle techniques, such as endobronchial ultrasound and transbronchial
      needle aspiration, oesophageal ultrasound and fine needle aspiration, or a
      combination of both, are preferred to any surgical staging technique. In cases of
      suspicious nodes and negative results using needle aspiration techniques,
      invasive surgical staging using mediastinoscopy or video-assisted thoracic
      surgery should be performed. In central tumours or N1 nodes, preoperative
      invasive staging is indicated.Restaging after induction therapy remains a
      controversial topic. Today, neither CT, PET nor PET/CT scans are accurate enough
      to make final further therapeutic decisions for mediastinal nodal involvement. An
      invasive technique providing cytohistological information is still recommended. 

PMID- 25976688
TI  - Pulmonary vascular response patterns during exercise in interstitial lung
      disease.
AB  - When overt pulmonary hypertension arises in interstitial lung disease (ILD), it
      contributes to exercise intolerance. We sought to determine the functional
      significance of abnormal pulmonary arterial pressure (PAP) responses to exercise
      in ILD.27 ILD patients and 11 age-matched controls underwent invasive
      cardiopulmonary exercise testing (iCPET). Mean PAP (mPAP) was indexed to cardiac
      output (Q'T) during exercise, with a mPAP-Q'T slope >=3 mmHg.min.L(-1) defined as
      an abnormal pulmonary vascular response.All control subjects had mPAP-Q'T slopes
      <3 mmHg.min.L(-1) (mean+/-sem 1.5+/-0.1 mmHg.min.L(-1)). 15 ILD patients had mPAP
      Q'T slopes >=3 mmHg.min.L(-1) (4.1+/-0.2 mmHg.min.L(-1)) and were labelled as
      having ILD plus pulmonary vascular dysfunction (PVD). Subjects without pulmonary
      hypertension and with mPAP-Q'T slopes <3 mmHg.min.L(-1) (1.9+/-0. 2 mmHg.min.L(
      1)) were labelled as ILD minus PVD (n=12). ILD+PVD and ILD-PVD patients did not
      differ in terms of age, sex, body mass index, pulmonary function testing or
      degree of exercise oxygen desaturation. Peak oxygen consumption was lower in
      ILD+PVD than in ILD-PVD (13.0+/-0.9 versus 17+/-1.1 mL.kg(-1).min(-1), p=0.012)
      and controls (19.8+/-1.7 mL.kg(-1).min(-1), p=0.003). ILD+PVD patients had
      increased dead space volume (VD)/tidal volume (VT) and minute ventilation/carbon
      dioxide production at the anaerobic threshold.In ILD, mPAP-Q'T slope >=3
      mmHg.min.L(-1) is associated with lower peak oxygen consumption, increased VD/VT
      and inefficient ventilation. While noninvasive parameters were unable to predict
      those with abnormal pulmonary vascular responses to exercise, iCPET-derived mPAP
      Q'T slope may aid in identifying physiologically significant, early pulmonary
      vascular disease in ILD.

PMID- 25976689
TI  - Proximal Segment Changes After Bilateral Sagittal Split Ramus Osteotomy in Facial
      Asymmetry Patients.
AB  - PURPOSE: To investigate the 3-dimensional postoperative changes in the proximal
      segments in patients with facial asymmetry according to the anteroposterior
      skeletal patterns. MATERIALS AND METHODS: A total of 51 patients with facial
      asymmetry who had undergone Le Fort I osteotomy and sagittal split ramus
      osteotomy (SSRO) with rigid fixation were classified according to their
      anteroposterior skeletal patterns. Cone-beam computed tomography (CBCT) data were
      obtained before (T0) and 6 months (T1) after surgery. The position, angulation,
      and distance of the proximal segment were measured from the CBCT superimposition.
      RESULTS: Comparing the T0 and T1 CBCT data, almost no significant differences
      were found in the condylar head position in any of the groups (P > .05), except
      for the axial condylar head position on the deviated side in the skeletal Class I
      group (P < .05) and the sagittal condylar head position on the deviated side in
      the skeletal Class III group (P < .05). However, the changes in the coronoid
      process and ramus down varied (P < .05), and these movements were related to
      changes in the ramal plane. Comparing the deviated and nondeviated sides,
      significant differences were found only in the skeletal Class I group (P < .05).
      CONCLUSIONS: The most influential factors affecting differences between the
      deviated and nondeviated sides in patients with facial asymmetry after bilateral
      SSRO could be the direction of the surgical movement of the distal segment of the
      mandible rather than its extent.

PMID- 25976687
TI  - A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD.
AB  - Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung
      disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed
      the first multidimensional measure to assess health-related quality of life
      (HRQoL) in adults with PCD (QOL-PCD).Following a literature review and expert
      panel meeting, open-ended interviews with patients investigated the impact of PCD
      on HRQoL in the UK and North America (n=21). Transcripts were content analysed to
      derive saturation matrices. Items were rated for relevance by patients (n=49).
      Saturation matrices, relevance scores, literature review, evaluation of existing
      measures, and expert opinion contributed to development of a preliminary
      questionnaire. The questionnaire was refined following cognitive interviews
      (n=18).Open-ended interviews identified a spectrum of issues unique to adults
      with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL
      PCD includes 48 items covering the following seven domains: Physical Functioning,
      Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and
      Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive
      testing confirmed that content was comprehensive and the items were well
      understood by respondents.Content validity and cognitive testing supported the
      items and structure. QOL-PCD has been translated into other languages and is
      awaiting psychometric testing. 

PMID- 25976690
TI  - Is Arthrocentesis Plus Platelet-Rich Plasma Superior to Arthrocentesis Alone in
      the Treatment of Temporomandibular Joint Osteoarthritis? A Randomized Clinical
      Trial.
AB  - PURPOSE: To compare the long-term clinical and radiologic outcomes of
      temporomandibular joint osteoarthritis (TMJ-OA) treated with arthrocentesis plus
      platelet-rich plasma (PRP) versus arthrocentesis alone. MATERIALS AND METHODS: A
      randomized clinical trial in adult patients with TMJ-OA referred to the authors'
      clinic from May 2012 through July 2013 was implemented. The sample was composed
      of 30 consecutive patients with TMJ-OA treated randomly with arthrocentesis alone
      (control group) or initial arthrocentesis plus PRP injection and then 4
      consecutive PRP injections (study group). The predictor variable was treatment
      technique. The outcome variables were visual analog scale evaluations
      (masticatory efficiency, joint sounds, and pain complaints), maximal interincisal
      opening, and cone-beam computed tomographic (CBCT) findings. Outcome variables
      were recorded preoperatively and 12 months postoperatively. Descriptive and
      bivariate statistics were computed, and significance was set at a P value less
      than .05. The paired t and Student t tests were used for intragroup and
      intergroup comparisons, respectively. RESULTS: The sample was composed of 47
      joints of 30 patients with OA (control group: 15 joints of 12 patients; mean age,
      35.08 +/- 14.84 yr; study group: 32 joints of 18 patients; mean age, 32.22 +/-
      14.32 yr). Joint sounds and general pain complaints decreased statistically in
      the 2 groups, whereas masticatory efficiency, painless interincisal opening, and
      lateral motion increased statistically only in the study group. However, only
      masticatory efficiency showed statistically greater improvement in the study
      group compared with the control group. CBCT evaluations showed that reparative
      remodeling of the osseous abnormalities occurred at rates of 87.5 and 46.6% in
      the study and control groups, respectively. CONCLUSIONS: These findings suggested
      that arthrocentesis and PRP injections constitute a safe and promising method for
      the treatment of TMJ-OA that is superior to arthrocentesis alone.

PMID- 25976691
TI  - An Assessment of the Quality of Life of Patients With Class III Deformities
      Treated With Orthognathic Surgery.
AB  - PURPOSE: To evaluate quality of life (QoL) from a broad perspective by a
      comparison of Turkish patients undergoing orthognathic surgery to correct Angle
      Class III skeletal deformity with a control group composed of participants
      without dentofacial deformity using general health, generic oral health, and
      condition-specific QoL approaches. MATERIALS AND METHODS: Thirty patients who
      underwent orthognathic surgery to correct Class III relations (monomaxillary and
      bimaxillary groups) and 30 participants with Class I skeletal structure and good
      dentofacial harmony (control group) were evaluated. Condition-specific QoL
      through a 22-item Orthognathic Quality of Life Questionnaire (OQLQ), generic oral
      health-related QoL through a 14-item Short-Form Oral Health Impact Profile (OHIP
      14), and generic health-related QoL through a 36-item Short-Form Health Survey
      (SF-36) were assessed. RESULTS: When the groups were compared, OQLQ scores showed
      a significant difference in the oral function domain only in the bimaxillary
      group (P < .05), and OHIP-14 scores showed significant differences in half the
      OHIP-14 subscale scores in the monomaxillary and bimaxillary groups (P < .05).
      The SF-36 scores showed significant differences only for the vitality domain in
      the monomaxillary group and the vitality and mental health domains in the
      bimaxillary group (P < .05). CONCLUSIONS: For condition-specific and health
      related QoL, the QoL of orthognathic surgical patients appeared to be similar to
      that of participants without dentofacial deformities. Oral health-related QoL of
      orthognathic surgical patients seemed moderately similar to that of participants
      without dentofacial deformities. The combined use of these methods is helpful for
      evaluating QoL from a larger perspective.

PMID- 25976692
TI  - Assessment of Volume and Height of the Coronoid Process in Patients With
      Different Facial Types and Skeletal Classes: A Cone-Beam Computed Tomography
      Study.
AB  - PURPOSE: To determine the height and volume of the mandibular coronoid process
      (CP) by cone-beam computed tomography (CBCT) and to identify the presence of any
      correlations of these measurements with age, gender, facial type, and skeletal
      class. MATERIALS AND METHODS: The sample consisted of 132 patients from a
      departmental routine patient base. After CBCT, CP height was determined using
      OnDemand 3D software (CyberMed, Seoul, Republic of Korea), and CP volume was
      obtained using ITK-SNAP 3.0 software (Cognitica, Philadelphia, PA). Measurements
      were subjected to analysis of covariance against facial type, skeletal class,
      gender, and age, with a significance level of 5%. RESULTS: CP height and volume
      were similar regardless of age, facial type, and skeletal class. However, the 2
      measurements were statistically different regarding gender, with larger values
      for men than for women. CONCLUSIONS: These observations suggest that gender is
      the only factor influencing the height and volume of the CP.

PMID- 25976693
TI  - An Epidemic Patchy Model with Entry-Exit Screening.
AB  - A multi-patch SEIQR epidemic model is formulated to investigate the long-term
      impact of entry-exit screening measures on the spread and control of infectious
      diseases. A threshold dynamics determined by the basic reproduction number R0 is
      established: The disease can be eradicated if R0 < 1, while the disease persists
      if R0 > 1. As an application, six different screening strategies are explored to
      examine the impacts of screening on the control of the 2009 influenza A (H1N1)
      pandemic. We find that it is crucial to screen travelers from and to high-risk
      patches, and it is not necessary to implement screening in all connected patches,
      and both the dispersal rates and the successful detection rate of screening play
      an important role on determining an effective and practical screening strategy.

PMID- 25976694
TI  - A Model for Mountain Pine Beetle Outbreaks in an Age-Structured Forest:
      Predicting Severity and Outbreak-Recovery Cycle Period.
AB  - The mountain pine beetle (MPB, Dendroctonus ponderosae), a tree-killing bark
      beetle, has historically been part of the normal disturbance regime in lodgepole
      pine (Pinus contorta) forests. In recent years, warm winters and summers have
      allowed MPB populations to achieve synchronous emergence and successful attacks,
      resulting in widespread population outbreaks and resultant tree mortality across
      western North America. We develop an age-structured forest demographic model that
      incorporates temperature-dependent MPB infestations. Stability of fixed points is
      analyzed as a function of (thermally controlled) MPB population growth rates and
      indicates the existence of periodic outbreaks that intensify as growth rates
      increase. We devise analytical methods to predict outbreak severity and duration
      as well as outbreak return time. After incorporating a spatial aspect and
      controlling initial stand demographic variation, the model predicts cycle periods
      that fall within observed outbreak return time ranges. To assess future MPB
      impact on forests, we use climate model projected temperatures with our model
      based approximation methods to predict potential severity of future outbreaks
      that reflect the effects of changing climate. 

PMID- 25976695
TI  - [Editorial].

PMID- 25976696
TI  - Centromeric chromatin and its dynamics in plants.
AB  - Centromeres are chromatin structures that are required for proper separation of
      chromosomes during mitosis and meiosis. The centromere is composed of centromeric
      DNA, often enriched in satellite repeats, and kinetochore complex proteins. To
      date, over 100 kinetochore components have been identified in various eukaryotes.
      Kinetochore assembly begins with incorporation of centromeric histone H3 variant
      CENH3 into centromeric nucleosomes. Protein components of the kinetochore are
      either present at centromeres throughout the cell cycle or localize to
      centromeres transiently, prior to attachment of microtubules to each kinetochore
      in prometaphase of mitotic cells. This is the case for the spindle assembly
      checkpoint (SAC) proteins in animal cells. The SAC complex ensures equal
      separation of chromosomes between daughter nuclei by preventing anaphase onset
      before metaphase is complete, i.e. the sister kinetochores of all chromosomes are
      attached to spindle fibers from opposite poles. In this review, we focus on the
      organization of centromeric DNA and the kinetochore assembly in plants. We
      summarize recent advances regarding loading of CENH3 into the centromere, and the
      subcellular localization and protein-protein interactions of Arabidopsis thaliana
      proteins involved in kinetochore assembly and function. We describe the
      transcriptional activity of corresponding genes based on in silico analysis of
      their promoters and cell cycle-dependent expression. Additionally, barley
      homologs of all selected A. thaliana proteins have been identified in silico, and
      their sequences and domain structures are presented.

PMID- 25976697
TI  - Many people in UK underestimate their weight.

PMID- 25976698
TI  - Silver nanoparticles affect the neural development of zebrafish embryos.
AB  - Silver nanoparticles (AgNPs) have been widely used in commercial products. This
      study aims to understand the impact of AgNPs on the early developmental stages in
      zebrafish (Danio rerio) embryos. Embryos were exposed to two sizes of AgNPs at
      three dose levels, as well to free Ag(+) ions, for a range of 4-96 h post
      fertilization (hpf). The acute exposure study showed that exposure to AgNPs
      affected the neurological development, and the exposed embryos exhibited
      anomalies such as small head with hypoplastic hindbrain, small eye and cardiac
      defects. At the molecular level, AgNPs altered the expression profiles of neural
      development-related genes (gfap, huC and ngn1), metal-sensitive metallothioneins
      and ABCC genes in exposed embryos. The expression of AhR2 and Cyp1A, which are
      usually considered to mediate polycyclic aromatic hydrocarbon toxicity, were also
      significantly changed. A size-dependent uptake of AgNPs was observed, whereby 4
      nm AgNPs were more efficiently taken up compared with the 10 nm-sized particles.
      Importantly, the head area accumulated AgNPs more efficiently than the trunk area
      of exposed zebrafish embryos. No free Ag(+) ions, which can be potentially
      released from the AgNP solutions, were detected. This study suggests that AgNPs
      could affect the neural development of zebrafish embryos, and the toxicity of
      AgNPs may be partially attributed to the comparatively higher uptake in the head
      area. These results indicate the potential neurotoxicity of AgNPs and could be
      extended to other aquatic organisms.

PMID- 25976699
TI  - Population pharmacokinetics of levofloxacin in Korean patients.
AB  - Levofloxacin (LVFX) has different effects depending on the area under the
      concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio.
      While AUC can be expressed as dose/clearance (CL), we measured serial
      concentrations of LVFX in Koreans and tried to set a Korean-specific equation,
      estimating the CL of the antibiotic. In total, 38 patients, aged 18-87 years,
      received once daily intravenous LVFX doses of 500 mg or 250 mg, depending on
      their renal function. Four plasma samples were obtained according to a D optimal
      sampling design. The population pharmacokinetic (PK) parameters of LVFX were
      estimated using non-linear mixed-effect modeling (NONMEM, ver. 7.2). The CL of
      LVFX was dependent on creatinine clearance (CLCR) as a covariate. The mean
      population PK parameters of LVFX in Koreans were as follows: CL (l/hour) = 6.19 *
      (CLCR/75)(1.32). The CL of LVFX in Koreans is expected to be lower than that in
      Western people. 

PMID- 25976700
TI  - Linking ryanodine receptor Ca(2+) leak and Na(+) current in heart: a day in the
      life of flecainide.

PMID- 25976702
TI  - [Not Available].

PMID- 25976701
TI  - Treatment maintenance duration of dual therapy with metformin and sitagliptin in
      type 2 diabetes: The ODYSSEE observational study.
AB  - AIM: The study compared the duration of maintenance of treatment in patients with
      type 2 diabetes (T2D) using dual therapy with either metformin and sitagliptin (M
      Sita) or metformin and a sulphonylurea (M-SU). MATERIALS AND METHODS: This
      observational study included adult patients with T2D who had responded
      inadequately to metformin monotherapy and therefore had started de-novo treatment
      with Met-Sita or Met-SU within the previous eight weeks. Patient follow-up and
      changes to treatment were performed according to their general practitioner's
      usual clinical practice. The primary outcome was time to change in treatment for
      whatever cause. HbA1c and symptomatic hypoglycaemia were also documented.
      RESULTS: The median treatment duration for patients in the M-Sita group (43.2
      months) was significantly longer (P < 0.0001) than in the M-SU group (20.2
      months). This difference persisted after adjusting for baseline differences and
      confounders. A similar reduction in HbA1c was noted in both arms (-0.6%), and the
      incidence of hypoglycaemia prior to treatment modification was lower with M-Sita
      (9.7%) than with M-SU (21.0%). Adverse events potentially related to treatment
      were reported in 2.8% (n = 52) and 2.7% (n = 20) of patients in the M-Sita and M
      SU arms, respectively. CONCLUSION: Under everyday conditions of primary diabetes
      care, dual therapy with M-Sita can be maintained for longer than M-SU. In
      addition, while efficacy, as measured by changes in HbA1c, was similar between
      treatments, the incidence of hypoglycaemia was lower in patients taking M-Sita.

PMID- 25976703
TI  - Effect of food intake on left and right ventricular systolic tissue Doppler
      measurements.
AB  - Systolic tissue Doppler measurements (s') have been used to measure the velocity
      in myocardial motion and are a valuable tool for evaluating the systolic function
      of the left and right ventricles. Digestion of food is known to significantly
      alter hemodynamics and may therefore affect s'. The effect of food intake on s'
      parameters has not yet been studied. We assessed whether s' is affected by food
      intake. Nineteen healthy subjects aged 26.2 +/- 4.2 years were investigated. s'
      was measured with pulsed tissue Doppler imaging in the right and left ventricles
      before the subjects ate a standardized meal and also 30 and 110 min after the
      meal. Three measurements were taken in each projection, and a mean value was
      calculated for each. s' increased significantly (P<0.05) from fasting to 30 min
      after food intake in every measured site except in the left inferolateral wall (P
      = 0.15, NS). Several, but not all, variables returned to base value 110 min after
      food intake. This study shows that food intake affects the tissue Doppler
      variables used to evaluate systolic heart function. Further studies are needed in
      older healthy subjects and older subjects with various cardiovascular diseases. 

PMID- 25976704
TI  - Rapid and sensitive analysis of 27 underivatized free amino acids, dipeptides,
      and tripeptides in fruits of Siraitia grosvenorii Swingle using HILIC-UHPLC
      QTRAP((r))/MS (2) combined with chemometrics methods.
AB  - In the present study, a new strategy based on chemical analysis and chemometrics
      methods was proposed for the comprehensive analysis and profiling of
      underivatized free amino acids (FAAs) and small peptides among various Luo-Han
      Guo (LHG) samples. Firstly, the ultrasound-assisted extraction (UAE) parameters
      were optimized using Plackett-Burman (PB) screening and Box-Behnken designs
      (BBD), and the following optimal UAE conditions were obtained: ultrasound power
      of 280 W, extraction time of 43 min, and the solid-liquid ratio of 302 mL/g.
      Secondly, a rapid and sensitive analytical method was developed for simultaneous
      quantification of 24 FAAs and 3 active small peptides in LHG at trace levels
      using hydrophilic interaction ultra-performance liquid chromatography coupled
      with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC
      QTRAP((r))/MS(2)). The analytical method was validated by matrix effects,
      linearity, LODs, LOQs, precision, repeatability, stability, and recovery.
      Thirdly, the proposed optimal UAE conditions and analytical methods were applied
      to measurement of LHG samples. It was shown that LHG was rich in essential amino
      acids, which were beneficial nutrient substances for human health. Finally, based
      on the contents of the 27 analytes, the chemometrics methods of unsupervised
      principal component analysis (PCA) and supervised counter propagation artificial
      neural network (CP-ANN) were applied to differentiate and classify the 40 batches
      of LHG samples from different cultivated forms, regions, and varieties. As a
      result, these samples were mainly clustered into three clusters, which
      illustrated the cultivating disparity among the samples. In summary, the
      presented strategy had potential for the investigation of edible plants and
      agricultural products containing FAAs and small peptides.

PMID- 25976705
TI  - Effects of paracrine factors on CD24 expression and neural differentiation of
      male germline stem cells.
AB  - Spermatogonial stem cells (SSCs) are adult male germ cells that develop after
      birth. Throughout the lifetime of an organism, SSCs sustain spermatogenesis
      through self-renewal and produce daughter cells that differentiate into
      spermatozoa. Several studies have demonstrated that SSCs can acquire pluripotency
      under appropriate culture conditions, thus becoming multipotent germline stem
      cells (mGSCs) that express markers of pluripotency in culture and form teratomas
      following transplantation into immunodeficient mice. In the present study, we
      generated neural precursor cells expressing CD24, a neural precursor marker, from
      pluripotent stem cell lines and demonstrated that these cells effectively
      differentiated along a neural lineage in vitro. In addition, we found that
      paracrine factors promoted CD24 expression during the neural differentiation of
      mGSCs. Our results indicated that the expression of CD24, enhanced by a
      combination of retinoic acid (RA), noggin and fibroblast growth factor 8 (FGF8)
      under serum-free conditions promoted neural precursor differentiation. Using a
      simple cell sorting method, we were able to collect neural precursor cells with
      the potential to differentiate from mGSCs into mature neurons and astrocytes in
      vitro.

PMID- 25976706
TI  - Prediction and prevention of allergic rhinitis: A birth cohort study of 20 years.
AB  - BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases,
      usually starting in the first 2 decades of life. Information on predictors, risk,
      and protective factors is missing because of a lack of long-term prospective
      studies. OBJECTIVE: Our aim was to examine early-life environmental and lifestyle
      determinants for AR up to age 20 years. METHODS: In 1990, the Multicenter Allergy
      Study included 1314 newborns in 5 German cities. Children were evaluated at 19
      time points. A Cox regression model examined the associations between 41
      independent early-life factors and onset of AR (as the primary outcome),
      including sensitization against aeroallergens and the secondary outcomes of
      nonallergic rhinitis and AR plus asthma. RESULTS: Two hundred ninety subjects had
      AR within 13,179 person years observed. The risk of AR was higher with a parental
      history of AR (adjusted hazard ratio [aHR], 2.49; 95% CI, 1.93-3.21), urticaria
      (aHR, 1.32; 95% CI, 1.00-1.74), or asthma (aHR, 1.29; 95% CI, 0.95-1.75). Early
      allergic sensitization (aHR, 4.53; 95% CI, 3.25-6.32), eczema within the first 3
      years of life (aHR, 1.83; 95% CI, 1.38-2.42), male sex (aHR, 1.28; 95% CI, 1.02
      1.61), and birthday in summer or autumn (aHR, 1.26; 95% CI, 1.00-1.58) were
      independent predictors of AR up to age 20 years. None of the other socioeconomic,
      environmental, lifestyle, pregnancy, and birth-related factors were associated
      with AR. CONCLUSION: Only nonmodifiable factors, particularly early allergic
      sensitization or eczema and parental AR, predicted AR up to age 20 years. No
      modifiable aspects of early-life environment or lifestyle were identified as
      targets for primary prevention.

PMID- 25976708
TI  - Clinical efficacy of polyvinyl siloxane impression materials using the one-step
      two-viscosity impression technique.
AB  - STATEMENT OF PROBLEM: Impression making is a challenging clinical procedure for
      both patients and dentists. PURPOSE: The purpose of this clinical study was to
      compare a recently introduced fast-setting polyvinyl siloxane (PVS) impression
      material with heavy body/light body (HB/LB) combination (Imprint 4; 3M ESPE)
      (experimental group) with a conventional PVS impression material with HB/LB
      combination (Imprint 3; 3M ESPE) (control group), using the 1-step 2-viscosity
      impression technique. MATERIAL AND METHODS: Two definitive impressions (1 of each
      material combination) were made of 20 crown preparations from 20 participants.
      The quality of impressions was rated by 3 evaluators (clinical evaluator,
      clinical operator, and dental technician) and by the patients for the level of
      comfort and taste of the impression materials. The order in which the 2
      impressions were made with each material combination was randomized for each
      crown preparation. A paired t test for paired means and McNemar test for paired
      proportions were used for statistical comparisons (alpha=.05). RESULTS:
      Participants rated the comfort of the impression making with the experimental
      group significantly higher than that with the control group (P=.001). No
      significant differences were found in participants' rating for the taste of the
      impression materials (P=.46). The viscosity for tray material was rated as
      significantly better for the control group by the clinical operator (P=.004). The
      readability of the impression and visibility around the finish line were rated as
      significantly better for the experimental group than for the control group
      (P<.001). Except for the ease of removal of the stone (RS), the ratings for the 2
      groups by the dental technician were similar. The ease of RS was rated as
      significantly better for the experimental group (P<.001). Eleven dies from the
      control and 9 from the experimental group were selected for fabrication of the
      definitive crowns (P=.65). CONCLUSION: Within the limitations of this clinical
      study, no significant differences were found in the overall clinical performance
      of the experimental and the control groups. Impressions made with both materials
      were clinically acceptable. Participants rated the comfort provided by the
      experimental group significantly better than that of the control group.

PMID- 25976707
TI  - Electronic laboratory quality assurance program: A method of enhancing the
      prosthodontic curriculum and addressing accreditation standards.
AB  - STATEMENT OF PROBLEM: An electronic quality assurance (eQA) program was developed
      to replace a paper-based system and to address standards introduced by the
      Commission on Dental Accreditation (CODA) and to improve educational outcomes.
      This eQA program provides feedback to predoctoral dental students on
      prosthodontic laboratory steps at New York University College of Dentistry.
      PURPOSE: The purpose of this study was to compare the eQA program of performing
      laboratory quality assurance with the former paper-based format. MATERIAL AND
      METHODS: Fourth-year predoctoral dental students (n=334) who experienced both the
      paper-based and the electronic version of the quality assurance program were
      surveyed about their experiences. Additionally, data extracted from the eQA
      program were analyzed to identify areas of weakness in the curriculum. RESULTS:
      The study findings revealed that 73.8% of the students preferred the eQA program
      to the paper-based version. The average number of treatments that did not pass
      quality assurance standards was 119.5 per month. This indicated a 6.34%
      laboratory failure rate. Further analysis of these data revealed that 62.1% of
      the errors were related to fixed prosthodontic treatment, 27.9% to partial
      removable dental prostheses, and 10% to complete removable dental prostheses in
      the first 18 months of program implementation. CONCLUSIONS: The eQA program was
      favored by dental students who have experienced both electronic and paper-based
      versions of the system. Error type analysis can yield the ability to create
      customized faculty standardization sessions and refine the didactic and clinical
      teaching of the predoctoral students. This program was also able to link patient
      care activity with the student's laboratory activities, thus addressing the
      latest requirements of the CODA regarding the competence of graduates in
      evaluating laboratory work related to their patient care.

PMID- 25976709
TI  - Load to failure of different zirconia abutments for an internal hexagon implant.
AB  - STATEMENT OF PROBLEM: Various zirconia abutment designs are available to restore
      implant systems. Fracture resistance is one of the criteria involved in selecting
      among these options. PURPOSE: The purpose of this in vitro study was to measure
      and compare load to failure for 5 zirconia abutments for an internally hexagon
      implant. MATERIAL AND METHODS: Five 4.1*11.5-mm Zimmer tapered screw-vent
      implants were individually secured in a loading apparatus, and 3 specimens of
      each of the 5 different abutments (Zimmer Contour with a Ti ring, anatomic
      contour Atlantis-Zr, anatomic-contour Inclusive-Zr, anatomic-contour Astra Tech
      ZirDesign, Legacy Straight Contoured abutment with Ti core) (N=15) were loaded at
      a 30-degree angle until the implant abutment complex failed. Data for load to
      failure were compared with analysis of variance and a Tukey-Kramer post hoc test
      (alpha=.05). RESULTS: The custom anatomic-contour abutment (Inclusive) showed the
      lowest load to fracture, and the stock anatomic-contour (AstraTech ZirDesign) the
      second lowest load to fracture. These were significantly lower than all other
      abutments (P<.05). The highest overall fracture strength was of a zirconia
      abutment with a titanium core-hexagon (Legacy Straight Contoured), which was
      significantly greater than all other abutments (P<.05). Anatomic-contour zirconia
      abutments fractured at an average of 275 N compared with the average fracture
      load of 842 N for zirconia abutments with titanium component (P<.05). CONCLUSION:
      The stock zirconia abutment with a titanium ring and the zirconia abutment with a
      titanium core-hexagon (Legacy Straight Contoured) had significantly greater
      fracture resistance than that of any of the 1-piece anatomic-contour zirconia
      abutments tested.

PMID- 25976710
TI  - Single-stage osseointegrated implants for nasal prosthodontic rehabilitation: A
      clinical report.
AB  - Malignant tumors in the nasal region may be treated by means of invasive surgical
      procedures, with large facial losses. Nasal prostheses, retained by
      osseointegrated facial implants, instead of plastic surgery, will, in most
      patients, offer good biomechanical and cosmetic results. This clinical report
      describes the prosthetic rehabilitation of a patient with nasal cancer who had
      the entire nasal vestibule removed in a single-stage surgical procedure in order
      to shorten the rehabilitation time. The nasal prosthesis was built on a 3-magnet
      bar and was made of platinum silicone with intrinsic pigmentation, thereby
      restoring the patient's appearance and self-esteem. The authors concluded that
      single-stage implants may reduce the rehabilitation time to as little as 1 month,
      and the correct use of materials and techniques may significantly improve the
      nasal prosthesis. 

PMID- 25976711
TI  - Use of a nanoparticulate carboxymethyl cellulose film containing sinigrin as an
      antimicrobial precursor to kill Escherichia coli O157:H7 on fresh beef.
AB  - Nanocomposite carboxymethyl cellulose films containing sinigrin (SNG) were
      prepared by stirring 2% (w/v) carboxymethyl cellulose (CMC) and 2% (w/v) glycerol
      (as a plasticizer) in distilled water with or without SNG (an antimicrobial
      precursor) as a 99% pure reagent (pSNG) or as a crude extract (cSNG). These films
      plus normal CMC film with or without SNG were tested on Escherichia coli O157:H7-
      inoculated beef for antimicrobial activity. Beef pieces measuring 6 * 5 * 2 cm(3)
      (L * W * H) were dipped in an E. coli O157:H7 broth suspension containing >8
      log10 CFU ml(-1) and were drained for 3 min over a sterile cloth. They were
      wrapped in CMC or NCMC films, placed in a high oxygen barrier film (Deli *1),
      vacuum-packaged and stored at 8 degrees C for 5, 8, 12 and 18 days. The CMC and
      NCMC films without SNG were not antimicrobial against E. coli O157:H7; however,
      NCMC and CMC films with SNG were highly antimicrobial. After 5 days at 8 degrees
      C, E. coli O157:H7 was reduced more than 4 log10 by the NCMC*pSNG film and this
      reduction remained almost the same until 18 days at 8 degrees C when E. coli
      O157:H7 was reduced >5 log10  CFU g(-1) meat. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Transparent nanoparticulate carboxymethyl cellulose (CMC) films containing
      sinigrin (SNG), an antimicrobial precursor, controlled surface contamination of
      packaged fresh beef by the pathogen Escherichia coli O157:H7 when stored at 8
      degrees C. Films with nanoparticulation that carried pure SNG or the naturally
      occurring SNG in Oriental mustard were significantly more antimicrobial than
      similar films without nanoparticulation. As films without sinigrin were not
      antimicrobial, the combinations studied showed that nanoparticulation of the
      packaging film enhanced delivery of the antimicrobial incorporated within the
      film.

PMID- 25976712
TI  - Persistent enhancement of bacterial motility increases tumor penetration.
AB  - Motile bacteria can overcome the transport limitations that hinder many cancer
      therapies. Active bacteria can penetrate through tissue to deliver treatment to
      resistant tumor regions. Bacterial therapy has had limited success, however,
      because this motility is heterogeneous, and within a population many individuals
      are non-motile. In human trials, heterogeneity led to poor dispersion and
      incomplete tumor colonization. To address these problems, a swarm-plate selection
      method was developed to increase swimming velocity. Video microscopy was used to
      measure the velocity distribution of selected bacteria and a microfluidic tumor
      on-a-chip device was used to measure penetration through tumor cell masses.
      Selection on swarm plates increased average velocity fourfold, from 4.9 to 18.7
      MUm/s (P < 0.05) and decreased the number of non-motile individuals from 51% to
      3% (P < 0.05). The selected phenotype was both robust and stable. Repeating the
      selection process consistently increased velocity and eliminated non-motile
      individuals. When selected strains were cryopreserved and subcultured for 30.1
      doublings, the high-motility phenotype was preserved. In the microfluidic device,
      selected Salmonella penetrated deeper into cell masses than unselected controls.
      By 10 h after inoculation, control bacteria accumulated in the front 30% of cell
      masses, closest to the flow channel. In contrast, selected Salmonella accumulated
      in the back 30% of cell masses, farthest from the channel. Selection increased
      the average penetration distance from 150 to 400 MUm (P < 0.05). This technique
      provides a simple and rapid method to generate high-motility Salmonella that has
      increased penetration and potential for greater tumor dispersion and clinical
      efficacy.

PMID- 25976714
TI  - Introduction to the WFSICCM Seoul 2015 Abstracts.

PMID- 25976713
TI  - Effectiveness of an Internet-based learning program on venous leg ulcer nursing
      care in home health care--study protocol.
AB  - AIM: To describe the study protocol for a study of the effectiveness of an
      internet-based learning program on venous leg ulcer nursing care (eVLU) in home
      health care. BACKGROUND: The prevalence of venous leg ulcers is increasing as
      population age. The majority of these patients are treated in a municipal home
      healthcare setting. However, studies show nurses' lack of knowledge of ulcer
      nursing care. DESIGN: Quasi-experimental study with pre- and postmeasurements and
      non-equivalent intervention and comparison groups. METHODS: During the study,
      nurses taking care of patients with a chronic leg ulcer in home health care in
      one Finnish municipality will use the eVLU. Nurses working in home health care in
      another Finnish municipality will not use it providing standard care. Nurses will
      complete three questionnaires during the study and they will also be observed
      three times at patients' homes. Nurses' perceived and theoretical knowledge is
      the primary outcome of the study. Funding for this study was received from the
      Finnish Foundation for Nursing Education in 2014. DISCUSSION: Data from this
      study will provide information about the effectiveness of an internet-based
      educational program. After completing the program nurses will be accustomed to
      using internet-based resources that can aid them in the nursing care of patients
      with a VLU. Nurses will also have better knowledge of VLU nursing care. This
      study is registered with the International Clinical Trials Registry, identifier
      NCT02224300.

PMID- 25976715
TI  - National prevalence of coronary heart disease and its relationship with human
      development index: A systematic review.
AB  - BACKGROUND: Coronary heart disease has become a major health concern over the
      past several decades. Several reviews have assessed the effects of socioeconomic
      status on the coronary heart disease epidemic in communities and countries, but
      only a few reviews have been performed at a global level. This study was to
      explore the relationship between the prevalence of coronary heart disease and
      socioeconomic development worldwide using the Human Development Index. DESIGN:
      Systematic review. METHODS: The data in this study were collected from the
      MEDLINE database. Cross-sectional studies reporting the prevalence of coronary
      heart disease until November 2014 were collected. The Human Development Index was
      sourced from the United Nations Development Programme Database and was used to
      measure the socioeconomic achievements of countries. Each country was classified
      as a developing or developed country based on its level of development according
      to the Human Development Index value. RESULTS: Based on the data analysis on the
      global level, coronary heart disease prevalence had no association with the
      national Human Development Index (rho = 0.07). However, there was a positive
      association between coronary heart disease prevalence and the national Human
      Development Index in developing countries, although a negative association
      existed in developed countries (rho = 0.47 and -0.34, respectively). In addition,
      the past decades have witnessed a growing coronary heart disease epidemic in
      developing countries, with reverse trends observed in developed countries (P =
      0.021 and 0.002, respectively). CONCLUSIONS: With the development of
      socioeconomic status, as measured by the Human Development Index, the prevalence
      of coronary heart disease is growing in developing countries, while declining in
      developed countries. Future research needs to pay more attention to the
      reasonable allocation of medical resources and control of coronary heart disease
      risk factors.

PMID- 25976718
TI  - Editorial: toward more reliable processes in health care.

PMID- 25976716
TI  - Corrigendum.

PMID- 25976719
TI  - Improving hand hygiene at eight hospitals in the United States by targeting
      specific causes of noncompliance.
AB  - BACKGROUND: Hospitals and infection prevention specialists have attempted to
      achieve high levels of compliance with hand hygiene protocols for many decades.
      Despite these efforts, measured performance is disappointingly low. METHODS: The
      Joint Commission Center for Transforming Healthcare convened teams of experts in
      performance improvement and infectious disease from eight hospitals for its hand
      hygiene quality improvement project, which was conducted from December 2008
      through September 2010. Together, they used Lean, Six Sigma, and change
      management methods to measure the magnitude of hand hygiene noncompliance, assess
      specific causes of hand hygiene failures, develop and test interventions targeted
      to specific causes, and sustain improved levels of performance. RESULTS: At
      baseline, hand hygiene compliance averaged 47.5% across all eight hospitals.
      Initial data revealed 41 different causes of hand hygiene noncompliance, which
      were condensed into 24 groups of causes. Key causes varied greatly among the
      hospitals. Each hospital developed and implemented specific interventions
      targeted to its most important causes of hand hygiene noncompliance. The
      improvements were associated with a 70.5% increase in compliance across the eight
      hospitals from 47.5% to 81.0% ( p < .001), a level of performance that was
      sustained for 11 months through the end of the project period. CONCLUSION: Lean,
      Six Sigma, and change management tools were used to identify specific causes of
      hand hygiene noncompliance at individual hospitals and target specific
      interventions to remedy the most important causes. This approach allowed each
      hospital to customize its improvement efforts by focusing on the causes most
      prevalent at its own facility. Such a targeted approach may be more effective,
      efficient, and sustainable than "one-size-fits-all" strategies.

PMID- 25976720
TI  - Beyond the collaborative: spreading effective improvement in hand hygiene
      compliance.
AB  - BACKGROUND: Data assessing the effectiveness of quality improvement (QI)
      collaboratives are mixed; spreading improvement beyond the original collaborative
      group has proved difficult. Little is known about whether organizations that did
      not participate in the collaborative are able to effectively employ interventions
      developed or implemented by those organizations that did participate. METHODS:
      The Joint Commission Center for Transforming Healthcare conducted a collaborative
      QI project with eight hospitals, using Lean, Six Sigma, and change management
      methods to improve hand hygiene compliance. Participating hospitals achieved a
      70.5% relative improvement (47.5% to 81.0%; p < .001). Following this project,
      working with an additional 19 hospitals, the Center created Web-based tools to
      enable health care organizations to use the same methods employed by the original
      eight hospitals without needing any knowledge or experience with Lean, Six Sigma,
      or change management. This Targeted Solutions Tool(r) (TST)(r) allowed
      organizations to discover the most important, specific causes of hand hygiene
      noncompliance in their facilities and to target interventions at those causes.
      RESULTS: In the first three years, 289 health care organizations used the TST to
      initiate 1,495 projects to improve hand hygiene compliance. Of the 769 projects
      at 174 organizations for which baseline and improvement data were available,
      average compliance improved from 57.9% to 83.5% (p < .0001). Similar improvement
      was observed in many clinical care settings, including ambulatory, long term
      care, inpatient pediatrics, critical care, and adult medical/surgical units.
      CONCLUSION: Hospitals and other health care organizations using the TST achieved
      levels of hand hygiene compliance comparable to those experienced by the
      participants in the original collaborative.

PMID- 25976721
TI  - Using lean management to reduce blood culture contamination.
AB  - BACKGROUND: Blood culture contamination (BCC) is a common and avoidable
      complication of patient care and incurs considerable cost. A quality improvement
      (QI) initiative was undertaken at a large Department of Veterans Affairs (VA)
      medical center to reduce the BCC rate. METHODS: Lean management QI methods,
      including a rapid process improvement workshop (RPIW), were used to identify root
      causes of variation in blood culture procedures and countermeasures (potential
      improvement strategies) to address each problem were developed. BCC rates were
      collected for five and one quarter years, including the pre-RPIW (baseline)
      period, and changes in the contamination rates were calculated. The observed
      change in BCC rates was compared to a forecast of the pre-RPIW trend and
      estimated BCCs avoided. Results for the primary medical center were compared with
      those of a similarly complex VA medical center during the same time periods using
      difference-in-differences methodology. RESULTS: Qualitative assessment of the
      processes of care identified four root cause problems, each of which was
      addressed with countermeasures. The BCC rate at the primary medical center
      decreased significantly from the baseline period in each year of follow-up,
      improving from 4.2% in the 19-month baseline period to 2.8% in the last 12 months
      of follow-up (April 2013-March 2014), while changes from baseline in the BCC rate
      at the comparison site were significant in only one year of follow-up. An
      estimated 261 BCCs were avoided at the primary medical center in the follow-up
      period. CONCLUSION: The QI initiative was successful in reducing BCC rates and in
      producing continued improvement for nearly four years of follow-up. Further study
      will determine if these results are generalizable to other settings.

PMID- 25976723
TI  - Inviting families to participate in care: a family involvement menu.

PMID- 25976724
TI  - To our readers.

PMID- 25976722
TI  - Implementation of a standardized postanesthesia care handoff increases
      information transfer without increasing handoff duration.
AB  - BACKGROUND: In the transition of a patient from the operating room (OR) to the
      postanesthesia care unit (PACU), it was hypothesized that (1) standardizing the
      members of sending and receiving teams and (2) requiring a structured handoff
      process would increase the overall amount of patient information transferred in
      the OR-to-PACU handoff process. METHODS: A prospective cohort study was conducted
      at a 311-bed freestanding academic pediatric hospital in Northern California. The
      intervention, which was conducted in February-March 2013, consisted of (1)
      requiring the sending team to include a surgeon, an anesthesiologist, and a
      circulating nurse, and the receiving team to include the PACU nurse; (2)
      standardizing the content of the handoff on the basis of literature-guided
      recommendations; and (3) presenting the handoff verbally in the I-PASS format.
      Data included amount of patient information transferred, duration of handoff,
      provider presence, and nurse satisfaction. RESULTS: Forty-one audits during the
      preimplementation phase and 45 audits during the postimplementation phase were
      analyzed. Overall information transfer scores increased significantly from a mean
      score of 49% to 83% (p < .0001). Twenty-two PACU nurse satisfaction surveys were
      completed after the preimplementation phase and 14 surveys were completed in the
      postimplementation phase. Paired mean total satisfaction scores increased from 36
      to 44 (p =. 004). The duration of the handoffs trended downward from 4.1 min to
      3.5 min (p = 0.10). CONCLUSION: A standardized, team-based approach to OR-to-PACU
      handoffs increased the quantity of patient information transferred, increased
      PACU nurse satisfaction, and did not increase the handoff duration.

PMID- 25976725
TI  - 2015 editorial advisory board.

PMID- 25976726
TI  - Tricho-hepato-enteric syndrome (THE-S): two cases and review of the literature.
AB  - Tricho-hepato-enteric syndrome (THE-S) is characterized by severe infantile
      diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic
      dysfunction. We report two cases of East Asian descent with THE-S who had
      remained undiagnosed despite extensive investigations but were diagnosed on whole
      exome sequencing (WES). Both cases presented with chronic diarrhea, failure to
      thrive, and recurrent infections. Case 1 had posteriorly rotated low set ears,
      mild retrognathia, and fine curly hypopigmented hair. She was managed with
      prolonged total parenteral nutrition and intravenous immunoglobulin infusions.
      Case 2 had sparse coarse brown hair as well as multiple lentigines and cafe-au
      lait macules. She was managed with amino acid-based formula. For both cases,
      routine investigations were inconclusive. WES in both cases showed biallelic
      truncating mutations in TTC37 (c.3507T>G;p.Y1169X and c.3601C>T;p.R1201X in case
      1 and c.3507T>G;p.Y1169X and c.154G>T;p.E52X in case 2), suggesting a diagnosis
      of THE-S. CONCLUSION: We present novel mutations in the TTC37 gene in two
      individuals of East Asian descent with the rare THE-S, detected by WES. Future
      identification of patients with THE-S and establishing genotype-phenotype
      correlations will aid in counseling the patients and their families. WHAT IS
      KNOWN: * Tricho-Hepato-Enteric syndrome (THE-S) is characterized by severe
      infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or
      hepatic dysfunction. * Complex patients with diagnostic dilemmas undergo
      extensive investigations. What is New: * This is a report of novel mutations in
      TTC37 in individuals of East Asian descent. * Whole exome sequencing (WES) can be
      useful in certain complex cases with diagnostic dilemmas.

PMID- 25976727
TI  - Representations of numerical sequences and the concept of middle in preschoolers.
AB  - The present study concerns preschoolers' understanding of the middle concept as
      it applies to numerical sequences. Previous research using implicit
      psychophysical assessment suggests that the numerical midpoint is embedded within
      numerical representations by 4 years of age. Here, we examined 3- to 5-year-olds'
      ability to identify the midpoint value in triplets of non-symbolic numbers when
      explicitly probed to do so. We found that whereas 4- and 5-year-olds were capable
      of explicit access to numerical midpoint values and showed ratio-dependent
      performance, a signature of the approximate number system (ANS), 3-year-olds
      performed at chance. Children's difficulty in identifying numerical midpoint
      values was not due to comparing multiple arrays, nor was it entirely due to a
      spatial association with the word "middle" used in the task. We speculate that
      explicit access to numerical midpoint values may be jointly supported by
      endogenous control of attentional mechanisms and the development of a mental
      number line. 

PMID- 25976728
TI  - Language as grist to the mill of cognition.
AB  - There is a growing consensus that natural language plays a significant role in
      our cognitive lives. However, this role of language is not adequately
      characterised. In this paper, I investigate the relationship between natural
      language and thinking and argue that thinking operates largely according to
      associationistic rules. Furthermore, I show that language is neither restricted
      to interfacing between a 'Language of Thought' and the conscious level, nor is it
      constitutively involved in thinking. Unlike available alternatives, the suggested
      view predicts and accommodates a large battery of empirical evidence.
      Furthermore, it avoids problems that associationistic views traditionally faced,
      e.g. problems of propositional thinking and compositionality of thought. 

PMID- 25976730
TI  - In reference to "Association of face-to-face handoffs and outcomes of
      hospitalized internal medicine patients".

PMID- 25976729
TI  - Galectin-3 levels are associated with right ventricular functional and
      morphologic changes in pulmonary arterial hypertension.
AB  - The response of the right ventricle (RV) to pulmonary arterial hypertension (PAH)
      involves changes in contractile function, chamber size, hypertrophy, and
      extracellular matrix (ECM). Galectin-3 (Gal-3) is a mediator of myocardial ECM
      metabolism and biomarker for left heart remodeling, yet its ability to reflect RV
      remodeling is unknown. We hypothesized that serum Gal-3 levels correlate with RV
      morphology and function in PAH, and that Gal-3 is associated with circulating
      markers of ECM. Fifteen subjects with PAH and 10 age-matched controls underwent
      same-day echocardiography, cardiac magnetic resonance (CMR) imaging, and
      phlebotomy for Gal-3 and ECM biomarkers including N-terminal propeptide of type
      III collagen type (PIIINP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and
      hyaluronic acid (HA). RV ejection fraction, end diastolic volume index, end
      systolic volume index, and mass index were calculated using CMR. Echocardiography
      was used to estimate RV systolic pressure and measure RV strain. Serum Gal-3,
      TIMP-1, and HA levels were all significantly increased in PAH subjects when
      compared to controls. Gal-3 correlated with RV ejection fraction (rho -0.44, p
      0.03), end diastolic volume index (rho 0.42, p 0.03), end systolic volume index
      (rho 0.44, p 0.027), mass index (rho 0.47, p 0.016), systolic pressure (rho 0.55,
      p < 0.001), and strain (rho 0.43, p 0.03). Gal-3 levels positively correlated
      with the ECM markers TIMP-1 and HA but not with PIIINP. In conclusion, Gal-3
      levels are associated with multiple indices of RV function and morphology. Gal-3
      may represent a novel biomarker for RV remodeling and associated ECM turnover in
      PAH. 

PMID- 25976731
TI  - Vincristine efficacy and safety in treating immune thrombocytopenia: a
      retrospective study of 35 patients.
AB  - Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune
      thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has
      yet to be demonstrated. We describe our clinical experience and recommend
      vincristine's correct place in ITP management. This retrospective study analysed
      data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C)
      ITP treated with VCR. The initial response rate, defined as >30 * 10(9)
      platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6-13]
      days. In ND and P ITP, even when previous therapies were inefficient, initial
      response was 87.5%, suggesting that this treatment could be used particularly in
      rescue. Median survival time, without failure or relapse, was 15 months (Kaplan
      Meier curve). Predictive factors (univariate analysis) of an initial and long
      term response were a small number of prior treatments received. However, at 2 yr,
      only seven patients had sustained response. Eight (23%) patients experienced
      adverse events: neuropathy for seven and bowel obstruction for one. Vincristine
      efficacy in ITP was confirmed, and it could be a good strategy for treating
      resistant ITP, especially in emergencies. In this era of new therapeutics, VCR
      deserves to remain on the list of ITP treatments because of its initial efficacy,
      safety and low cost.

PMID- 25976732
TI  - Fast and fully-scalable synthesis of reduced graphene oxide.
AB  - Exfoliation of graphite is a promising approach for large-scale production of
      graphene. Oxidation of graphite effectively facilitates the exfoliation process,
      yet necessitates several lengthy washing and reduction processes to convert the
      exfoliated graphite oxide (graphene oxide, GO) to reduced graphene oxide (RGO).
      Although filtration, centrifugation and dialysis have been frequently used in the
      washing stage, none of them is favorable for large-scale production. Here, we
      report the synthesis of RGO by sonication-assisted oxidation of graphite in a
      solution of potassium permanganate and concentrated sulfuric acid followed by
      reduction with ascorbic acid prior to any washing processes. GO loses its
      hydrophilicity during the reduction stage which facilitates the washing step and
      reduces the time required for production of RGO. Furthermore, simultaneous
      oxidation and exfoliation significantly enhance the yield of few-layer GO. We
      hope this one-pot and fully-scalable protocol paves the road toward out of lab
      applications of graphene. 

PMID- 25976734
TI  - Paraneoplastic myeloneuropathy in a man with breast cancer.

PMID- 25976735
TI  - Hot punching of high-aspect-ratio 3D polymeric microstructures for drug delivery.
AB  - Hot punching with two different strategies has been demonstrated as a new method
      of fabricating high aspect ratio 3D microstructures for drug delivery. It has
      been shown that this process is highly versatile with good replication fidelity
      and yield. 

PMID- 25976733
TI  - Short-term natural history of high-risk human papillomavirus infection in mid
      adult women sampled monthly.
AB  - Characterizing short-term HPV detection patterns and viral load may inform HPV
      natural history in mid-adult women. From 2011-2012, we recruited women aged 30-50
      years. Women submitted monthly self-collected vaginal samples for high-risk HPV
      DNA testing for 6 months. Positive samples were tested for type-specific HPV DNA
      load by real-time PCR. HPV type-adjusted linear and Poisson regression assessed
      factors associated with (i) viral load at initial HPV detection and (ii) repeat
      type-specific HPV detection. One-hundred thirty-nine women (36% of 387 women with
      >=4 samples) contributed 243 type-specific HR HPV infections during the study;
      54% of infections were prevalent and 46% were incident. Incident (vs. prevalent)
      detection and past pregnancy were associated with lower viral load, whereas
      current smoking was associated with higher viral load. In multivariate analysis,
      current smoking was associated with a 40% (95% CI: 5-87%) increase in the
      proportion of samples that were repeatedly positive for the same HPV type,
      whereas incident (vs. prevalent) detection status and past pregnancy were each
      associated with a reduction in the proportion of samples repeatedly positive
      (55%, 95% CI: 38-67% and 26%, 95% CI: 10-39%, respectively). In a separate
      multivariate model, each log10 increase in viral load was associated with a 10%
      (95% CI: 4-16%) increase in the proportion of samples repeatedly positive.
      Factors associated with repeat HPV detection were similar to those observed in
      longer-term studies, suggesting that short-term repeat detection may relate to
      long-term persistence. The negative associations between incident HPV detection
      and both viral load and repeat detection suggest that reactivation or
      intermittent persistence was more common than new acquisition. 

PMID- 25976736
TI  - Cognitive dissonance in food and nutrition-A review.
AB  - The study of cognitive dissonance in food and nutrition has been relatively under
      developed. This review paper looks at food and/or food-related studies that have
      utilized cognitive dissonance as a primary construct in a priori theorization and
      hypothesis-formulation, examining the ways in which the dissonance construct has
      been used and its corresponding effects on various food-related outcomes in those
      studies. Current gaps and critical issues underlying cognitive dissonance
      investigation in food and nutrition research are also identified and discussed.

PMID- 25976737
TI  - Epidemiological characteristics of bloodstream infections in patients with
      different degrees of liver disease.
AB  - Observational retrospective study to evaluate the etiology, the outcome and the
      risk factors of bloodstream infections (BSIs) in patients with liver disease. One
      hundred and forty-eight BSIs were diagnosed (infection rate: 0.60 per 100 days of
      hospital stay), 62 BSIs (41.9 %) were associated with Gram-positive bacteria
      (infection rate: 0.25 per 100 days of hospital stay) and 80 (54.4 %) with Gram
      negative bacteria (infection rate: 0.32 per 100 days of hospital stay). Admission
      associated mortality was higher in patients with BSI than in those without BSI
      (20.6 versus 5.0 %, p < 0.001). Patients with cirrhosis had an increased risk to
      develop a BSI compared with patients with chronic hepatitis, specifically for
      Gram-positive (and Staphylococcus spp)-related BSI.

PMID- 25976738
TI  - Relationship between biodistribution of a novel thymidine phosphorylase (TP)
      imaging probe and TP expression levels in normal mice.
AB  - OBJECTIVE: Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine
      nucleoside salvage pathway and its expression is upregulated in a wide variety of
      solid tumors. In mice, we previously observed high and specific accumulation
      levels of our TP imaging probe, radioiodinated 5-iodo-6-[(2
      iminoimidazolidinyl)methyl]uracil (IIMU) not only in high-TP-expressing tumors,
      but also in the liver and small intestine. To clarify the reason for the high
      accumulation levels of radioiodinated IIMU in the liver and small intestine, we
      investigated the expression levels of TP in mice in comparison with the
      biodistribution of radioiodinated IIMU ((123)I-IIMU). METHODS: BALB/cCrSlc mice
      were injected with (123)I-IIMU, and the radioactivity levels [%ID/g (normalized
      to a mouse of 25 g body weight)] in the tissues of interest were determined 0.5,
      1, 3 and 24 h after the injection (n = 5, each time point). To determine the
      expression levels of TP, BALB/cCrSlc and ddy mice (n = 3/each strain) were
      euthanized, and the heart, liver, lung, spleen, kidney, stomach, small intestine,
      large intestine and brain were collected. The mRNA and protein expression levels
      of TP in these organs were examined by quantitative reverse transcription
      polymerase chain reaction and western blot analyses, respectively. RESULTS: In
      BALB/cCrSlc mice administered (123)I-IIMU, markedly high radioactivity levels
      were observed in the liver [1.568 +/- 0.237 (%ID/g)] and small intestine [0.506
      +/- 0.082 (%ID/g)], whereas those in the other tissues were fairly low [<0.010 +/
      0.003 (%ID/g)] 30 min after the injection. The highest expression levels of TP
      mRNA were also observed in the liver and small intestine among the tissues
      tested. Immunoblotting showed intense immunoreactive bands of the TP protein for
      the liver and small intestine, whereas no notable bands were detected for other
      tissues. Similar expression profiles of TP mRNA and protein were observed in ddy
      mice. CONCLUSION: We confirmed TP expression in various tissues of mice at the
      mRNA and protein levels: high TP expression levels were observed in the liver and
      small intestine. These high TP expression levels are consistent with the high
      accumulation levels of (123)I-IIMU in these tissues. Our results may provide
      important information about the physiological accumulation of (123)I-IIMU, which
      may be useful for the clinical diagnostic imaging of TP.

PMID- 25976739
TI  - In vitro generation of functional dendritic cells differentiated from CD34
      negative cells isolated from human umbilical cord blood.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells that play a
      crucial role in the initiation of an immune response. As DC-based therapeutic
      applications is increasing, large-scale DC production is required for
      transplantation. Human umbilical cord blood (UCB) has been shown to contain a
      rare and precious population of hematopoietic stem cells (HSCs), which can give
      rise to DCs. The CD34 antigen has been widely used as a cell surface marker to
      identify HSCs. In this study, we used CD34 antibody to isolate CD34(+) and CD34(
      ) cells and compared the ability to differentiate into DCs. We used a two-step
      method combined with the magnetic bead sorting system to isolate CD34(+) and
      CD34(-) cells from human UCB. Analysis of cellular properties and functionality
      using a migration assay and T cell proliferation assay revealed no significant
      differences between CD34(+) cells and CD34(-) cells in their ability to generate
      DCs. 

PMID- 25976740
TI  - Downregulation of MDC1 and 53BP1 by short hairpin RNA enhances radiosensitivity
      in laryngeal carcinoma cells.
AB  - DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) are among the
      most cytotoxic types of DNA damage. The DNA damage response (DDR) may be a reason
      for the cancer cell resistance to radiotherapy using IR. Identified as critical
      upstream mediators of the phosphorylation of ataxia telangiectasia-mutated (ATM)
      pathway, mediator of DNA damage checkpoint 1 (MDC1) and p53-binding proteins 1
      (53BP1) may affect the radiosensitivity of tumor cells. In the present study, we
      generated two HEP-2 cell lines with a stable knockdown of MDC1 or 53BP1 with
      short hairpin RNA (shRNA), respectively, and investigated the effect of MDC1 and
      53BP1 on cell radiosensitivity, cell cycle distribution and the formation of cell
      foci. Downregulation of the two proteins reduced the number of clonogenic cells
      that treated with IR. Accumulation of G2/M phase cells was detected after the
      MDC1 and 53BP1 downregulation. These results indicated that the expression of
      MDC1 or 53BP1 limited tumor cell sensitivity to radiotherapy and may play an
      important role in the DNA repair progression. Furthermore, the MDC1 foci was
      identified and presented in the 53BP1-inhibited cells. By contrast, the 53BP1
      foci was absent from the MDC1-inhibited cells. The results confirmed that the
      recruitment of 53BP1 into the foci occurred in an MDC1-dependent manner.

PMID- 25976741
TI  - What can we talk about, in which language, in what way and with whom? Sami
      patients' experiences of language choice and cultural norms in mental health
      treatment.
AB  - BACKGROUND: The Sami in Norway have a legal right to receive health services
      adapted to Sami language and culture. This calls for a study of the significance
      of language choice and cultural norms in Sami patients' encounters with mental
      health services. OBJECTIVES: To explore the significance of language and cultural
      norms in communication about mental health topics experienced by Sami patients
      receiving mental health treatment to enhance our understanding of linguistic and
      cultural adaptation of health services. METHODS: Data were collected through
      individual interviews with 4 Sami patients receiving mental health treatment in
      Northern Norway. A systematic text reduction and a thematic analysis were
      employed. FINDINGS: Two themes were identified:(I) Language choice is influenced
      by language competence, with whom one talks and what one talks about.Bilingualism
      was a resource and natural part of the participants' lives, but there were
      limited possibilities to speak Sami in encounters with health services. A
      professional working relationship was placed on an equal footing with the
      possibility to speak Sami. CONCLUSION: Sami patients' language choice in
      different communication situations is influenced by a complexity of social and
      cultural factors. Sami patients have varying opinions about and preferences for
      what they can talk about, in which language, in what way and with whom.
      Bilingualism and knowledge about both Sami and Norwegian culture provide latitude
      and enhanced possibilities for both patients and the health services. The
      challenge for the health services is to allow for and safeguard such individual
      variations within the cultural framework of the patients.

PMID- 25976742
TI  - Adequate vitamin D levels in a Swedish population living above latitude 63 
      degrees N: The 2009 Northern Sweden MONICA study.
AB  - BACKGROUND: Even though vitamin D is mainly produced by exposure to sunlight,
      little is known regarding vitamin D levels in populations living in sub-Arctic
      areas with little or no daylight during winter. OBJECTIVE: We describe
      distributions of vitamin D3 and the prevalence of adequate levels in a population
      living above 63  degrees N. DESIGN: We sampled 1,622 randomly selected subjects,
      aged 25-74 years, between January and May, 2009, as part of the Northern Sweden
      MONICA study (69.2% participation rate). By using HPLC, 25(OH) vitamin D3 was
      analysed. Levels used for definitions were deficient, D3<25 nmol/l (<10 ng/ml);
      insufficient, D3 25-49.9 nmol/l (10-20 ng/ml); and adequate, D3 >= 50 nmol/l (20
      ng/ml). RESULTS: Mean (median) level of vitamin D3 was 65.2 (63.6) nmol/l in men
      and 71.0 (67.7) nmol/l in women. Adequate levels were found in 79.2%, more often
      in women (82.7%) than in men (75.6%). Only 0.7% of the population were vitamin D3
      deficient but 23.1% of men and 17.1% of women had insufficient levels. Levels of
      vitamin D3 increased with age and insufficient status was most common among those
      aged 25-34 years, 41.0% in men and 22.3% in women. If subjects using vitamin D
      supplementation are excluded, the population level of D3 is 1-2 nmol/l lower than
      in the general population across sex- and age groups. There were no differences
      between the northern or the southern parts, between urban or rural living or
      according to educational attainment. Those subjects born outside of Sweden or
      Finland had lower levels. CONCLUSION: The large majority living close to the
      Arctic Circle in Sweden have adequate D3 levels even during the second half of
      the dark winter. Subjects with D3 deficiency were uncommon but insufficient
      levels were often found among young men.

PMID- 25976743
TI  - The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer
      patients with metastatic bone disease.
AB  - BACKGROUND: We compared the activity of denosumab with zoledronic acid for
      delaying or preventing hypercalcaemia of malignancy (HCM) in patients with
      advanced cancer and bone metastases or with multiple myeloma. METHODS: Patient
      level data were combined from two identically designed, randomised, double-blind,
      active-controlled, phase III trials of advanced cancer patients with breast
      cancer and other solid tumours (excluding breast or prostate cancer) or multiple
      myeloma. End-points included time to first on-study HCM, time to first and
      subsequent on-study HCM, proportion of patients experiencing HCM and proportion
      of patients experiencing recurrent HCM. RESULTS: Denosumab significantly delayed
      the time to first on-study HCM, representing a 37% reduction in the hazard ratio
      (HR) compared with zoledronic acid (HR, 0.63; 95% confidence interval (CI): 0.41
      0.98; P = 0.042) and reduced the risk of developing recurrent HCM (time to first
      and subsequent on-study HCM) by 52% (rate ratio, 0.48; 95% CI: 0.29-0.81; P =
      0.006). The median time on study was 12.9 months. Fewer patients receiving
      denosumab compared with zoledronic acid experienced an HCM event (1.7% versus
      2.7%; P = 0.028). Of the 84 patients experiencing an HCM event, 40% of those
      receiving zoledronic acid experienced >1 event of HCM compared with 31% of those
      receiving denosumab. CONCLUSION: Denosumab treatment was more efficacious than
      treatment with zoledronic acid in delaying or preventing HCM in advanced cancer
      patients with breast cancer, other solid tumours or multiple myeloma.

PMID- 25976744
TI  - Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol.
AB  - BACKGROUND: Na/K-ATPase (NKA) is inhibited by perillyl alcohol (POH), a
      monoterpene used in the treatment of tumors, including brain tumors. The NKA
      alpha1 subunit is known to be superexpressed in glioblastoma cells (GBM). This
      isoform is embedded in caveolar structures and is probably responsible for the
      signaling properties of NKA during apoptosis. In this work, we showed that POH
      acts in signaling cascades associated with NKA that control cell proliferation
      and/or cellular death. METHODS: NKA activity was measured by the amount of non
      radioactive Rb(+) incorporation into cultured GBM cell lines (U87 and U251) and
      non-tumor cells (mouse astrocytes and VERO cells). Cell viability was measured by
      lactate dehydrogenase levels in the supernatants of POH-treated cells. Activated
      c-Jun N-terminal Kinase (JNK) and p38 were assessed by western blotting.
      Apoptosis was detected by flow cytometry and immunocytochemistry, and the release
      of interleukins was measured by ELISA. RESULTS: All four cell types tested showed
      a similar sensitivity for POH. Perillic acid (PA), the main metabolite of POH,
      did not show any effect on these cells. Though the cell viability decreased in a
      dose-dependent manner when cells were treated with POH, the maximum cytotoxic
      effect of PA obtained was 30% at 4 mM. 1.5 mM POH activated p38 in U87 cells and
      JNK in both U87 and U251 cells as well as mouse astrocytes. Dasatinib (an
      inhibitor of the Src kinase family) and methyl beta-cyclodextrin (which promotes
      cholesterol depletion in cell membranes) reduced the POH-induced activation of
      JNK1/2 in U87 cells, indicating that the NKA-Src complex participates in this
      mechanism. Inhibition of JNK1/2 by the JNK inhibitor V reduced the apoptosis of
      GBM cells that resulted from POH administration, indicating the involvement of
      JNK1/2 in programmed cell death. 1.5 mM POH increased the production of
      interleukin IL-8 in the U251 cell supernatant, which may indicate a possible
      strategy by which cells avoid the cytotoxic effects of POH. CONCLUSIONS: A
      signaling mechanism mediated by NKA may have an important role in the anti-tumor
      action of POH in GBM cells.

PMID- 25976746
TI  - Chloroplast Genome Evolution in the Euglenaceae.
AB  - Over the last few years multiple studies have been published outlining
      chloroplast genomes that represent many of the photosynthetic euglenid genera.
      However, these genomes were scattered throughout the euglenophyceaean
      phylogenetic tree, and focused on comparisons with Euglena gracilis. Here, we
      present a study exclusively on taxa within the Euglenaceae. Six new chloroplast
      genomes were characterized, those of Cryptoglena skujai, E. gracilis var.
      bacillaris, Euglena viridis, Euglenaria anabaena, Monomorphina parapyrum, and
      Trachelomonas volvocina, and added to six previously published chloroplast
      genomes to determine if trends existed within the family. With this study: at
      least one genome has now been characterized for each genus, the genomes of
      different strains from two taxa were characterized to explore intraspecific
      variability, and a second taxon has been characterized for the genus Monomorphina
      to examine intrageneric variability. Overall results showed a large amount of
      variability among the genomes, though a few trends could be identified both
      within Euglenaceae and within Euglenophyta. In addition, the intraspecific
      analysis indicated that the similarity of a genome sequence between strains was
      taxon dependent, and the intrageneric analysis indicated that the majority of the
      evolutionary changes within the Euglenaceae occurred intergenerically. 

PMID- 25976745
TI  - Objective measurement of visual resolution using the P300 to self-facial images.
AB  - OBJECTIVE: To assess visual acuity objectively "beyond V1", the P300 event
      related potential is a promising candidate and closely associated with conscious
      perception. However, the P300 can be willfully modulated, a disadvantage for
      objective visual acuity estimation. Faces are very salient stimuli and difficult
      to ignore. Here, we present a P300-type paradigm to assess visual acuity with
      faces. METHODS: Gray-scale portraits of the respective subject served as oddball
      stimuli (probability 1/7), scrambled versions of these as the standard stimuli
      (probability 6/7). Furthermore, stimuli were spatially high-pass filtered (at 0,
      2.2, 4.2 and 8.3 cpd), making them recognizable only with sufficient acuity.
      Acuity was systematically reduced by dioptric blur, chosen individually to render
      faces unrecognizable when high-passed at >= 4.2 cpd. EEG was recorded from 11
      subjects at 32 scalp positions and re-referenced to the average of TP9 and TP10.
      One of the rare face variants was designated as target, for which a button had to
      be pressed. RESULTS: The event-related potential was dominated by the P300 at 300
      800 ms. All subjects had a significant (P < 0.05) P300 for 0- to 8.3-cpd
      filtering. When vision was blurred, the fraction of significant P300 responses to
      8.3-cpd filtered faces dropped to 18%, but stayed at 100% for 4.2 cpd. Another
      component, the vertex positive potential (VPP) at 170 ms, was undetectable in
      most participants with blur and all levels of filtering, even when the images
      were recognizable. CONCLUSIONS: The study demonstrates the feasibility of a face
      based P300 approach to objectively assess visual acuity. The sensitivity to
      stimulus degradation was comparable to that of a grating-based approach as
      previously reported. An unexpected finding was the differing behavior of the P300
      and the VPP. The VPP was quite sensitive to high-pass filtering, while the P300
      sustained stronger filtering, although for its generation, the faces must also be
      discriminated from scrambled faces.

PMID- 25976747
TI  - Proteomic analysis of porcine endometrial tissue during peri-implantation period
      reveals altered protein abundance.
AB  - In mammals, successful pregnancy depends upon the readiness of uterus for
      implantation, followed by correct communication between the endometrium and the
      developing conceptus. The objective of this study was to elucidate changes in
      protein abundance associated with progression of estrous cycle and pregnancy from
      Day 9 to Day 12. We analyzed porcine endometrial tissue lysates by 2D-DIGE.
      Abundance of several proteins was altered depending upon the pregnancy status of
      animals. MALDI-TOF/TOF was used to identify a number of these proteins.
      Endometrial proteins that increased from Day 9 to Day 12 of cycle included
      annexin A4, beta-actin, apolipoprotein, ceruloplasmin and afamin. Changes in
      protein abundances associated with conceptus secreted factors, including
      haptoglobin, prolyl-4-hydroxylase, aldose-reductase and transthyretin, were also
      observed. Functional analysis revealed that endometrial proteins with altered
      abundance on Day 12 irrespective of the reproductive status were related to
      growth and remodeling, acute phase response and free radical scavenging, whereas
      transport and small molecule biochemistry were the functions activated in the
      pregnant endometrium as compared to the cyclic endometrium. These data provide
      information on dynamic physiological processes associated with uterine
      endometrial function of the cyclic and pregnant endometrium during period of
      maternal recognition of pregnancy in pigs and may potentially demonstrate a
      protein profile associated with successful pregnancy. BIOLOGICAL SIGNIFICANCE: In
      pigs, the fertility rates are generally very high but the early embryonic loss
      that occurs during the second and third weeks of gestation critically affects the
      potential litter size. Temporal changes that take place in the uterine
      environment during the period of early pregnancy in pigs and a cross-talk between
      the uterus and the embryo play an important role in embryonic survival and
      successful pregnancy. A better understanding of the molecular changes associated
      with these processes will pave way for understanding of endometrial functions and
      help towards increasing embryo survival. In this study, we present a 2D-DIGE
      based analysis of changes in porcine endometrial proteome that are associated
      with progression of cycle and progression of pregnancy. The network analysis of
      the results clearly revealed the pathways that are involved in rendering the
      endometrium receptive to the presence of embryo and also the changes that are
      result of molecular communication between the endometrium and the conceptuses.
      This comprehensive identification of proteomic changes in the porcine endometrium
      could be a foundation for targeted studies of proteins and pathways potentially
      involved in abnormal endometrial receptivity, placentation and embryo loss.

PMID- 25976748
TI  - Proteomic responses to a methyl viologen-induced oxidative stress in the wild
      type and FerB mutant strains of Paracoccus denitrificans.
AB  - FerB is a cytoplasmic flavoprotein from the soil bacterium Paracoccus
      denitrificans with a putative role in defense against oxidative stress. To
      further explore this hypothesis, we compared protein variations upon methyl
      viologen treatment in wild-type and FerB mutant strains by a quantitative
      proteomic analysis based on iTRAQ-3DLC-MS/MS analysis. The proteins showing the
      most prominent increase in abundance were assigned to carbon fixation and sulfur
      assimilatory pathways. By employing these proteins as indirect markers, oxidative
      stress was found to be 15% less severe in the wild-type than in the FerB
      deficient mutant cells. Oxidative stress altered the levels of proteins whose
      expression is dependent on the transcriptional factor FnrP. The observed down
      regulation of the fnrP regulon members, most notably that of nitrous oxide
      reductase, was tentatively explained by an oxidative degradation of the [4Fe-4S]
      center of FnrP leading to a protein form which no longer activates transcription.
      While the level of FerB remained relatively constant, two proteins homologous to
      FerB accumulated during oxidative stress. When their genes were expressed in
      Escherichia coli, neither of the protein products contained a bound flavin,
      whereas they both had a high activity of flavin reductase, one preferentially
      utilizing NADH and the other NADPH. 

PMID- 25976749
TI  - Sarin-induced brain damage in rats is attenuated by delayed administration of
      midazolam.
AB  - Sarin poisoned rats display a hyper-cholinergic activity including
      hypersalivation, tremors, seizures and death. Here we studied the time and dose
      effects of midazolam treatment following nerve agent exposure. Rats were exposed
      to sarin (1.2 LD50, 108 MUg/kg, im), and treated 1 min later with TMB4 and
      atropine (TA 7.5 and 5 mg/kg, im, respectively). Midazolam was injected either at
      1 min (1 mg/kg, im), or 1 h later (1 or 5 mg/kg i.m.). Cortical seizures were
      monitored by electrocorticogram (ECoG). At 5 weeks, rats were assessed in a water
      maze task, and then their brains were extracted for biochemical analysis and
      histological evaluation. Results revealed a time and dose dependent effects of
      midazolam treatment. Rats treated with TA only displayed acute signs of sarin
      intoxication, 29% died within 24h and the ECoG showed seizures for several hours.
      Animals that received midazolam within 1 min survived with only minor clinical
      signs but with no biochemical, behavioral, or histological sequel. Animals that
      lived to receive midazolam at 1h (87%) survived and the effects of the delayed
      administration were dose dependent. Midazolam 5 mg/kg significantly counteracted
      the acute signs of intoxication and the impaired behavioral performance,
      attenuated some of the inflammatory response with no effect on morphological
      damage. Midazolam 1mg/kg showed only a slight tendency to modulate the cognitive
      function. In addition, the delayed administration of both midazolam doses
      significantly attenuated ECoG compared to TA treatment only. These results
      suggest that following prolonged seizure, high dose midazolam is beneficial in
      counteracting adverse effects of sarin poisoning.

PMID- 25976750
TI  - Executive summary. Management of urinary tract infection in solid organ
      transplant recipients: Consensus statement of the Group for the Study of
      Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious
      Diseases and Clinical Microbiology (SEIMC) and the Spanish Network for Research
      in Infectious Diseases (REIPI).
AB  - Urinary tract infections (UTI) are one of the most common infections in solid
      organ transplant (SOT) recipients. A systematic review was performed to assess
      the management of UTI in SOT recipients. Recommendations are provided on the
      management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in
      SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the
      role of infection in kidney graft rejection or dysfunction are reviewed. Finally,
      recommendations on antimicrobials and immunosuppressant interactions are also
      included.

PMID- 25976751
TI  - Molecular characterization of Staphylococcus aureus isolated from humans related
      to a livestock farm in Spain, with detection of MRSA-CC130 carrying mecC gene: A
      zoonotic case?
AB  - OBJECTIVES: To conduct a study of Staphylococcus aureus carriage in members of a
      livestock-farmer's family with different degrees of animal contact, and to
      characterize the recovered isolates. METHODS: Nasal samples from 11 members of
      the family were taken in three sampling periods (every six months) (n=31), and 9
      skin samples from superficial lesions were also obtained in 5 of them. Samples
      were analyzed for S. aureus susceptible (MSSA) and resistant to methicillin
      (MRSA). S. aureus isolates were tested for antibiotic-resistance phenotype and
      genotype and for the detection of virulence and IEC-system genes. Molecular
      typing of isolates was also performed (spa- and multilocus-sequence typing).
      RESULTS: Eighteen S. aureus isolates were recovered (1 MRSA and 17 MSSA) in the
      40 samples analyzed. S. aureus was detected in nasal and skin samples of 7/11 and
      4/5 of tested humans, respectively. The MRSA strain was detected in the skin
      lesion of a farmer with high animal contact, and carried the mecC gene, and was
      typed as ST130-CC130-t843. The 17 MSSA isolates were ascribed to 9 different spa
      types and sequence types included in the clonal complexes CC22, CC30, CC45,
      CC121, and in the livestock-associated lineages CC9 and CC133. Six strains
      harbored eta or tsst-1 genes. Three of 18 strains lacked the immune-evasion
      cluster (IEC) genes (MRSA-ST130, MSSA-ST1333, and MSSA-ST133), and the remaining
      isolates were ascribed to IEC type-A or -B. CONCLUSIONS: Animal-associated S.
      aureus lineages were detected in samples of the farmer's family, highlighting the
      detection of MSSA-CC133 and mecC-MRSA-ST130.

PMID- 25976752
TI  - Performance of cobas 4800((r)) and HPV genotype-specific distribution in
      opportunistic cervical cancer screening in Madrid.

PMID- 25976753
TI  - Antibiotic susceptibility of Listeria monocytogenes in Argentina.
AB  - INTRODUCTION: Listeria monocytogenes is the causative agent of listeriosis, a
      food-borne disease that mainly affects pregnant women, the elderly, and
      immunocompromised patients. The primary treatment of choice of listeriosis is the
      combination of ampicillin or penicillin G, with an aminoglycoside, classically
      gentamicin. The second-choice therapy for patients allergic to beta-lactams is
      the combination of trimethoprim with a sulfonamide (such as co-trimoxazole). The
      aim of this study was to analyze the antimicrobial susceptibility profile of
      strains isolated from human infections and food during the last two decades in
      Argentina. METHODS: The minimal inhibitory concentration (MIC) of 8 antimicrobial
      agents was determined for a set of 250 strains of L. monocytogenes isolated in
      Argentina during the period 1992-2012. Food-borne and human isolates were
      included in this study. The antibiotics tested were ampicillin, chloramphenicol,
      trimethoprim-sulfamethoxazole, erythromycin, gentamicin, penicillin G,
      tetracycline and rifampicin. Breakpoints for penicillin G, ampicillin and
      trimethoprim-sulfamethoxazole were those given in the CLSI for L. monocytogenes.
      CLSI criteria for staphylococci were applied to the other antimicrobial agents
      tested. Strains were serotyped by PCR, and confirmed by an agglutination method.
      RESULTS: Strains recovered from human listeriosis patients showed a prevalence of
      serotype 4b (71%), with the remaining 29% corresponding to serotype 1/2b.
      Serotypes among food isolates were distributed as 62% serotype 1/2b and 38%
      serotype 4b. All antimicrobial agents showed good activity. CONCLUSION: The
      strains of L. monocytogenes isolated in Argentina over a period of 20 years
      remain susceptible to antimicrobial agents, and that susceptibility pattern has
      not changed during this period.

PMID- 25976755
TI  - Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal
      muscle rejuvenation.
AB  - Ursolic acid (UA) is a lipophilic compound, which highly found in apple peels. UA
      has some certain features, of the most important is its anabolic effects on
      skeletal muscles, which in turn plays a prominent role in the aging process,
      encouraged us to evaluate skeletal muscle rejuvenation. This study seeks to
      address the two following questions: primarily, we wonder to know if UA increases
      anti-aging biomarkers (SIRT1 and PGC-1alpha) in the isolated satellite cells, to
      pave the way for satellite cells proliferation. The results revealed that UA
      elevated the expression of SIRT1 (~ 35 folds) and PGC-1alpha (~ 175 folds) genes.
      The other question that needs to be asked, however, is to understand whether it
      is possible to generalize the in vitro findings to in vivo. For this, a study was
      designed to investigate the effects of UA on the cellular energy status in the
      animal models (C57BL/6 mice). We found that UA decreased cellular energy charges
      such as ATP (~ 3 times) and ADP (~ 18 times). With respect to the role of UA in
      energy expenditure and as an anti-aging biomarker, one might wonder to elucidate
      skeletal muscle rejuvenation as well as satellite cells proliferation and
      neomyogenesis. The results illustrated that UA boosted neomyogenesis through
      enhancing the number of satellite cells. In addition, rejuvenation effects of UA
      on the skeletal muscle promptly encouraged us to reexamine the performance of
      skeletal muscles. The results indicated that UA through increasing myoglobin
      expression (~ 2 folds) accompanied with transforming of glycolytic to fast
      oxidative status chiefly and slow-twitch muscle fibers. To the best of our
      knowledge, it seems that UA might be considered as a potential candidate for
      treatment of pathological conditions associated with muscular atrophy and
      dysfunction, including skeletal muscle atrophy, amyotrophic lateral sclerosis
      (ALS), sarcopenia and metabolic diseases of the muscles.

PMID- 25976754
TI  - Management of urinary tract infection in solid organ transplant recipients:
      Consensus statement of the Group for the Study of Infection in Transplant
      Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical
      Microbiology (SEIMC) and the Spanish Network for Research in Infectious Diseases
      (REIPI).
AB  - BACKGROUND: Urinary tract infections (UTIs) are one of the most common infections
      in solid organ transplant (SOT) recipients. METHODS: Experienced SOT researchers
      and clinicians have developed and implemented this consensus document in support
      of the optimal management of these patients. A systematic review was conducted,
      and evidence levels based on the available literature are given for each
      recommendation. This article was written in accordance with international
      recommendations on consensus statements and the recommendations of the Appraisal
      of Guidelines for Research and Evaluation II (AGREE II). RESULTS: Recommendations
      are provided on the management of asymptomatic bacteriuria, and prophylaxis and
      treatment of UTI in SOT recipients. The diagnostic-therapeutic management of
      recurrent UTI and the role of infection in kidney graft rejection or dysfunction
      are reviewed. Finally, recommendations on antimicrobials and immunosuppressant
      interactions are also included. CONCLUSIONS: The latest scientific information on
      UTI in SOT is incorporated in this consensus document.

PMID- 25976757
TI  - Rapid Activation of Glucocorticoid Receptors in the Prefrontal Cortex Mediates
      the Expression of Contextual Conditioned Fear in Rats.
AB  - The aim of the present study was to investigate the role of glucocorticoids in
      medial prefrontal cortex (mPFC) activity and the expression of contextual
      conditioned fear (freezing). Rats were pretreated with vehicle or metyrapone, a
      corticosterone synthesis blocker, and exposed to a context previously paired with
      footshocks. Freezing and Fos-protein expression in different mPFC regions were
      assessed. Exposure to the aversive context led to increased freezing and Fos
      expression in the prelimbic (PrL), anterior cingulate areas 1 and 2 (Cg1/Cg2).
      Pretreatment with metyrapone decreased freezing and Fos expression in these
      areas. Administration of spironolactone, an MR antagonist, in the PrL before the
      test decreased freezing. Pretreatment with RU38486, a glucocorticoid receptor
      (GR) antagonist, reduced this effect of spironolactone, suggesting that the
      effects of this MR antagonist may be attributable to a redirection of endogenous
      corticosterone actions to GRs. Consistent with this result, the decrease in
      freezing that was induced by intra-PrL injections of corticosterone was
      attenuated by pretreatment with RU38486 but not spironolactone. These findings
      indicate that corticosterone release during aversive conditioning influences mPFC
      activity and the retrieval of conditioned fear memory indicating the importance
      of balance between MR:GR-mediated effects in this brain region in this process.

PMID- 25976758
TI  - Evolutionary defined role of the mitochondrial DNA in fertility, disease and
      ageing.
AB  - BACKGROUND: The endosymbiosis of an alpha-proteobacterium and a eubacterium a
      billion years ago paved the way for multicellularity and enabled eukaryotes to
      flourish. The selective advantage for the host was the acquired ability to
      generate large amounts of intracellular hydrogen-dependent adenosine
      triphosphate. The price was increased reactive oxygen species (ROS) inside the
      eukaryotic cell, causing high mutation rates of the mitochondrial DNA (mtDNA).
      According to the Muller's ratchet theory, this accumulation of mutations in
      asexually transmitted mtDNA would ultimately lead to reduced reproductive fitness
      and eventually extinction. However, mitochondria have persisted over the course
      of evolution, initially due to a rapid, extreme evolutionary reduction of the
      mtDNA content. After the phylogenetic divergence of eukaryotes into animals,
      fungi and plants, differences in evolution of the mtDNA occurred with different
      adaptations for coping with the mutation burden within these clades. As a result,
      mitochondrial evolutionary mechanisms have had a profound effect on human
      adaptation, fertility, healthy reproduction, mtDNA disease manifestation and
      transmission and ageing. An understanding of these mechanisms might elucidate
      novel approaches for treatment and prevention of mtDNA disease. METHODS: The
      scientific literature was investigated to determine how mtDNA evolved in animals,
      plants and fungi. Furthermore, the different mechanisms of mtDNA inheritance and
      of balancing Muller's ratchet in these species were summarized together with the
      consequences of these mechanisms for human health and reproduction. RESULTS:
      Animal, plant and fungal mtDNA have evolved differently. Animals have compact
      genomes, little recombination, a stable number of genes and a high mtDNA copy
      number, whereas plants have larger genomes with variable gene counts, a low mtDNA
      copy number and many recombination events. Fungal mtDNA is somewhere in between.
      In plants, the mtDNA mutation rate is kept low by effective ROS defence and
      efficient recombination-mediated mtDNA repair. In animal mtDNA, these mechanisms
      are not or less well-developed and the detrimental mutagenesis events are
      controlled by a high mtDNA copy number in combination with a genetic bottleneck
      and purifying selection during transmission. The mtDNA mutation rates in animals
      are higher than in plants, which allow mobile animals to adapt more rapidly to
      various environmental conditions in terms of energy production, whereas static
      plants do not have this need. Although at the level of the species, these
      mechanisms have been extremely successful, they can have adverse effects for the
      individual, resulting, in humans, in severe or unpredictably segregating mtDNA
      diseases, as well as fertility problems and unhealthy ageing. CONCLUSIONS:
      Understanding the forces and processes that underlie mtDNA evolution among
      different species increases our knowledge on the detrimental consequences that
      individuals can have from these evolutionary end-points. Alternative outcomes in
      animals, fungi and plants will lead to a better understanding of the inheritance
      of mtDNA disorders and mtDNA-related fertility problems. These will allow the
      development of options to ameliorate, cure and/or prevent mtDNA diseases and
      mtDNA-related fertility problems.

PMID- 25976756
TI  - Flatworms have lost the right open reading frame kinase 3 gene during evolution.
AB  - All multicellular organisms studied to date have three right open reading frame
      kinase genes (designated riok-1, riok-2 and riok-3). Current evidence indicates
      that riok-1 and riok-2 have essential roles in ribosome biosynthesis, and that
      the riok-3 gene assists this process. In the present study, we conducted a
      detailed bioinformatic analysis of the riok gene family in 25 parasitic flatworms
      (platyhelminths) for which extensive genomic and transcriptomic data sets are
      available. We found that none of the flatworms studied have a riok-3 gene, which
      is unprecedented for multicellular organisms. We propose that, unlike in other
      eukaryotes, the loss of RIOK-3 from flatworms does not result in an evolutionary
      disadvantage due to the unique biology and physiology of this phylum. We show
      that the loss of RIOK-3 coincides with a loss of particular proteins associated
      with essential cellular pathways linked to cell growth and apoptosis. These
      findings indicate multiple, key regulatory functions of RIOK-3 in other metazoan
      species. Taking advantage of a known partial crystal structure of human RIOK-1,
      molecular modelling revealed variability in nucleotide binding sites between
      flatworm and human RIOK proteins. 

PMID- 25976759
TI  - The influence of friends and siblings on the physical activity and screen viewing
      behaviours of children aged 5-6 years: a qualitative analysis of parent
      interviews.
AB  - OBJECTIVES: The present study uses qualitative data to explore parental
      perceptions of how their young child's screen viewing and physical activity
      behaviours are influenced by their child's friends and siblings. DESIGN:
      Telephone interviews were conducted with parents of year 1 children (age 5-6
      years). Interviews considered parental views on a variety of issues related to
      their child's screen viewing and physical activity behaviours, including the
      influence that their child's friends and siblings have over such behaviours.
      Interviews were transcribed verbatim and analysed using deductive content
      analysis. Data were organised using a categorisation matrix developed by the
      research team. Coding and theme generation was iterative and refined throughout.
      Data were entered into and coded within N-Vivo. SETTING: Parents were recruited
      through 57 primary schools located in Bristol and the surrounding area that took
      part in the B-ProAct1v study. PARTICIPANTS: Fifty-three parents of children aged
      5-6 years. RESULTS: Parents believe that their child's screen viewing and
      physical activity behaviours are influenced by their child's siblings and
      friends. Friends are considered to have a greater influence over the structured
      physical activities a child asks to participate in, whereas the influence of
      siblings is more strongly perceived over informal and spontaneous physical
      activities. In terms of screen viewing, parents suggest that their child's
      friends can heavily influence the content their child wishes to consume, however,
      siblings have a more direct and tangible influence over what a child watches.
      CONCLUSIONS: Friends and siblings influence young children's physical activity
      and screen viewing behaviours. Child-focused physical activity and screen viewing
      interventions should consider the important influence that siblings and friends
      have over these behaviours.

PMID- 25976760
TI  - Exploring risk of experiencing intimate partner violence after HIV infection: a
      qualitative study among women with HIV attending postnatal services in Swaziland.
AB  - OBJECTIVE: To explore risks of experiencing intimate partner violence (IPV) after
      HIV infection among women with HIV in a postnatal care setting in Swaziland.
      DESIGN: A qualitative semistructured in-depth interview study, using thematic
      analysis with deductive and inductive coding, of IPV experiences after HIV
      infection extracted from service-integration interview transcripts. SETTING:
      Swaziland. PARTICIPANTS: 19 women with HIV, aged 18-44, were purposively sampled
      for an in-depth interview about their experiences of services, HIV and IPV from a
      quantitative postnatal cohort participating in an evaluation of HIV and
      reproductive health services integration in Swaziland. RESULTS: Results indicated
      that women were at risk of experiencing IPV after HIV infection, with 9 of 19
      disclosing experiences of physical violence and/or coercive control post-HIV. IPV
      was initiated through two key pathways: (1) acute interpersonal triggers (eg,
      status disclosure, mother-to-child transmission of HIV) and (2) chronic normative
      tensions (eg, fertility intentions, initiating contraceptives). CONCLUSIONS: The
      results highlight a need to mitigate the risk of IPV for women with HIV in
      shorter and longer terms in Swaziland. While broader changes are needed to
      resolve gender disparities, practical steps can be institutionalised within
      health facilities to reduce, or avoid increasing, IPV pathways for women with
      HIV. These might include mutual disclosure between partners, greater engagement
      of Swazi males with HIV services, and promoting positive masculinities that
      support and protect women. TRIAL REGISTRATION NUMBER: NCT01694862.

PMID- 25976761
TI  - Awareness of cervical cancer prevention among mothers of adolescent daughters in
      Korea: qualitative research.
AB  - OBJECTIVES: Korean adolescent girls are unprepared for cervical cancer prevention
      due to the lack of a mandatory policy regarding human papilloma virus (HPV)
      vaccination and school health education regarding cervical cancer. The aim of
      this study was to determine how aware mothers are about cervical cancer
      prevention in their adolescent daughters, with a view to developing strategies
      for expanding primary cervical cancer prevention for adolescent girls through the
      mothers' involvement. DESIGN: A qualitative design was employed. Nine mothers
      with adolescent daughters participated in this study and were interviewed using
      open-ended questions. The themes were extracted by content analysis. SETTING: A
      general living area in Seoul, South Korea. PARTICIPANTS: The snowball method was
      used to select mothers. RESULTS: Five themes emerged. In general, the mothers'
      awareness of cervical cancer was not clear, and they exhibited a lack of
      awareness of the importance of having a regular Papanicolaou screening test. The
      mothers recognised that they were role models for their daughters, and realised
      and accepted the necessity of educating their daughters regarding cervical
      cancer; however, they perceived barriers related to the prevention of cervical
      cancer in their daughters. The mothers recommended enforcing sex education in
      schools and the provision of financial support for HPV vaccination. CONCLUSIONS:
      The mothers' awareness and preparedness with respect to the prevention of
      cervical cancer in their adolescent daughters were low and inadequate. Mothers
      should be informed and motivated to play a role in the education of their
      daughters regarding cervical cancer prevention. Strategies for disseminating
      information regarding early cervical cancer prevention for adolescent girls are
      recommended by communicating with both the girls and their mothers and providing
      them with education regarding cervical cancer prevention.

PMID- 25976762
TI  - Time-varying impact of comorbidities on mortality after liver transplantation: a
      national cohort study using linked clinical and administrative data.
AB  - OBJECTIVE: We assessed the impact of comorbidity on mortality in three periods
      after liver transplantation (first 90 days, 90 days-5 years and 5-10 years).
      DESIGN: Prospective cohort study using records from the UK Liver Transplant Audit
      (UKLTA) linked to Hospital Episode Statistics (HES), an administrative database
      of hospital admissions in the English National Health Service (NHS).
      Comorbidities relevant for liver transplantation were identified from the 10th
      revision of the International Classification of Diseases (ICD-10) codes in HES
      records of admissions in the year preceding their operation. Multivariable Cox
      regression was used to estimate HRs for three different time periods after liver
      transplantation. SETTING: All liver transplant centres in the NHS hospitals in
      England. PARTICIPANTS: Adults who received a first elective liver transplant
      between April 1997 and March 2010 in the linked UKLTA-HES database. OUTCOMES:
      Patient mortality in three different time periods after transplantation. RESULTS:
      Among 3837 recipients, 45.1% had comorbidities. Recipients with cardiovascular
      disease had statistically significantly higher mortality in all three periods
      after transplantation (first 90 days: HR=2.0; 95% CI 1.4 to 2.9, 90 days-5 years:
      1.6; 1.2 to 2.2, beyond 5 years: 2.8; 1.7 to 4.4). Prior congestive cardiac
      failure (3.2; 2.1 to 4.9) significantly increased mortality only in the first 90
      days. History of non-hepatic malignancy appeared to increase risk over all
      periods, but significantly only in the first 90 days (1.9; 1.0 to 3.6). A
      diagnosis of connective tissue disease, dementia, diabetes, chronic pulmonary and
      renal disease did not have a significant impact on mortality in any period.
      CONCLUSIONS: The impact of comorbidities present at the time of transplantation
      changes with time after transplantation. Renal disease, pulmonary disease and
      diabetes had no impact on mortality in contrast to previous reports.

PMID- 25976764
TI  - The prevalence, impact and cost of chronic non-cancer pain in Irish primary
      schoolchildren (PRIME-C): protocol for a longitudinal school-based survey.
AB  - INTRODUCTION: Previous research has indicated that pain influences children's
      daily lives, resulting in absence from school, sleep problems, poor school
      performance and problems with social activities. Our study aims to characterise
      the nature, extent, impact and cost of chronic pain among Irish children. METHODS
      AND ANALYSIS: Using cluster-systematic random sampling, primary schools will be
      invited to participate and 6000 5-12-year-olds asked to complete questionnaires
      in school classrooms, at time points 1 year apart. Questionnaires will use
      internationally valid psychometric measures to assess a range of quality of life
      factors and chronic pain indicators among children, with corresponding
      parental/primary caregiver questions, which will be completed at home. Data will
      also be gathered on the cost of chronic pain. Space will be given for comments on
      how pain impacts on participants' lives and possible coping mechanisms. ETHICS
      AND DISSEMINATION: Ethical approval has been granted by the Research Ethics
      Committee, National University of Ireland, Galway. Dissemination of results will
      be via journal articles and conference presentations on the various aspects of
      the study (ie, prevalence, impact and economic cost of chronic pain among 5-12
      year-olds living in Ireland).

PMID- 25976763
TI  - Serological investigation to identify risk factors for post-flood infectious
      diseases: a longitudinal survey among people displaced by Typhoon Morakot in
      Taiwan.
AB  - OBJECTIVES: After Typhoon Morakot struck Taiwan in 2009, thousands of Taiwanese
      citizens were displaced to shelters for several weeks. Others were placed in
      urban communities where they had family members. This study aimed to investigate
      serological status in both groups and identify risk factors associated with
      seroconversion of infectious diseases. DESIGN: A longitudinal survey. SETTING:
      All experimental and clinical investigations were performed in a tertiary
      teaching hospital. PARTICIPANTS: A total of 288 displaced persons (96 males and
      192 females) were recruited and complete follow-up data through two rounds of
      sampling were collected. The average age was 58.42 years (range 31-87 years).
      INTERVENTIONS: First, serum specimens were collected between December 2009 and
      January 2010, 4-5 months after the typhoon. The second round of specimen
      collection was carried out after 6 months. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The primary outcome measured was serological status of vaccine
      preventable droplet-borne infectious diseases (ie, measles, mumps, rubella) and
      water-borne diseases (ie, amoebiasis and leptospirosis). The secondary outcome
      was identification of risk factors for seroconversion using univariate and
      multivariate analyses. RESULTS: Complete data were available for all 288
      displaced persons (114 from the shelter group; 174 from the community group).
      Seroconversion of Entamoeba histolytica was observed in 128 (44.4%) participants,
      with a significantly higher rate in the shelter group than in the community group
      (56.1% vs 36.8%; p=0.001). There were 10 cases of rubella seroconversion. After
      adjusting for medical history, hypertension and hyperlipidaemia, shelter stay was
      associated with higher risk for seroconversion (OR=2.055, 95% CI 1.251 to 3.374;
      p=0.004). Amoebiasis was more evident in the shelter group, although the
      manifestations were mild. CONCLUSIONS: Our results suggested that (1) a clean
      water supply is essential postdisaster, especially in crowded shelters, and (2)
      vaccination programmes should be extended to populations at higher risk for post
      disaster displacement or to those with weakened immune status.

PMID- 25976765
TI  - Evaluation of a tobacco prevention programme among teenagers in Sweden.
AB  - OBJECTIVE: To study the prevalence of tobacco use among teenagers, to evaluate a
      tobacco prevention programme and to study factors related to participation in the
      prevention programme. DESIGN AND SETTING: Population-based prospective cohort
      study. METHOD: Within the Obstructive Lung disease in Northern Sweden (OLIN)
      studies, a cohort study about asthma in schoolchildren started in 2006. All
      children aged 7-8 years in three municipalities were invited to a questionnaire
      survey and 2585 (96%) participated. The cohort was followed up at age 11-12 years
      (n=2612, 95% of invited) and 14-15 years (n=2345, 88% of invited). In 2010, some
      of the children in the OLIN cohort (n=447) were invited to a local tobacco
      prevention programme and 224 (50%) chose to participate. RESULTS: At the age of
      14-15 years, the prevalence of daily smoking was 3.5%. Factors related to smoking
      were female sex, having a smoking mother, participation in sports and lower
      parental socioeconomic status (SES). The prevalence of using snus was 3.3% and
      risk factors were male sex, having a smoking mother, having a snus-using father
      and non-participation in the prevention programme. In the prevention programme,
      the prevalence of tobacco use was significantly lower among the participants
      compared with the controls in the cohort. Factors related to non-participation
      were male sex, having a smoking mother, lower parental SES and participation in
      sports. CONCLUSIONS: The prevalence of tobacco use was lower among the
      participants in the tobacco prevention programme compared with the non
      participants as well as with the controls in the cohort. However, the observed
      benefit of the intervention may be overestimated as participation was biased by
      selection.

PMID- 25976767
TI  - Effectiveness of Cognitive Processing Therapy for Male and Female U.S. Veterans
      With and Without Military Sexual Trauma.
AB  - Military sexual trauma (MST) affects approximately 2% and 36% of male and female
      veterans, respectively, (e.g., Allard, Gregory, Klest, & Platt, 2011). Although
      the deleterious consequences of MST have been clearly established, few studies
      have explored treatment effectiveness for this population. Using archival data
      from a residential treatment program, the current study explored the
      effectiveness of cognitive processing therapy (CPT) in treating full or
      subthreshold posttraumatic stress disorder (PTSD) to compare U.S. veterans
      reporting an MST index trauma (MST-IT) to those without MST-IT. Of the 481
      participants, 40.7% endorsed MST-IT. Multiway frequency analyses were utilized to
      compare men and women with and without MST on baseline demographic variables.
      Hierarchical linear models were constructed to investigate treatment outcome by
      MST status and sex. Results showed that 44.8%, 23.8%, and 19.6% of the variation
      in clinician- and self-reported PTSD and depression symptoms were explained by
      three models. Scores on all outcome measures significantly decreased over time
      for both groups. Additionally, women demonstrated a sharper decrease in PTSD
      symptoms over time than men. Lastly, men who reported MST-IT had higher PTSD
      symptoms than men without MST-IT on average. With no control group or random
      assignment, preliminary findings suggest residential treatment including CPT may
      be effective for MST-IT regardless of sex.

PMID- 25976766
TI  - Synthesis and Evaluation of a Novel Deguelin Derivative, L80, which Disrupts ATP
      Binding to the C-terminal Domain of Heat Shock Protein 90.
AB  - The clinical benefit of current anticancer regimens for lung cancer therapy is
      still limited due to moderate efficacy, drug resistance, and recurrence.
      Therefore, the development of effective anticancer drugs for first-line therapy
      and for optimal second-line treatment is necessary. Because the 90-kDa molecular
      chaperone heat shock protein (Hsp90) contributes to the maturation of numerous
      mutated or overexpressed oncogenic proteins, targeting Hsp90 may offer an
      effective anticancer therapy. Here, we investigated antitumor activities and
      toxicity of a novel deguelin-derived C-terminal Hsp90 inhibitor, designated L80.
      L80 displayed significant inhibitory effects on the viability, colony formation,
      angiogenesis-stimulating activity, migration, and invasion of a panel of non
      small cell lung cancer cell lines and their sublines with acquired resistance to
      paclitaxel with minimal toxicity to normal lung epithelial cells, hippocampal
      cells, vascular endothelial cells, and ocular cells. Biochemical analyses and
      molecular docking simulation revealed that L80 disrupted Hsp90 function by
      binding to the C-terminal ATP-binding pocket of Hsp90, leading to the disruption
      of the interaction between hypoxia-inducible factor (HIF)-1alpha and Hsp90,
      downregulation of HIF-1alpha and its target genes, including vascular endothelial
      growth factor (VEGF) and insulin-like growth factor 2 (IGF2), and decreased the
      expression of various Hsp90 client proteins. Consistent with these in vitro
      findings, L80 exhibited significant antitumor and antiangiogenic activities in
      H1299 xenograft tumors. These results suggest that L80 represents a novel C
      terminal Hsp90 inhibitor with effective anticancer activities with minimal
      toxicities. 

PMID- 25976768
TI  - Serum chemokine network correlates with chemotherapy in non-small cell lung
      cancer.
AB  - OBJECTIVE: Inflammation plays an important role in the microenvironment of lung
      cancer. The present study aimed to evaluate the association of inflammatory
      biomarker networks with chemotherapies for patients with non-small cell lung
      cancer (NSCLC). METHODS: The sera of healthy non-smokers (n = 14) and patients
      with NSCLC (n = 50), 36 with adenocarcinoma and 14 with squamous cell carcinoma,
      were collected. Healthy patients were untreated, while those with NSCLC were
      either chemotherapy-naive or had received one and two courses of chemotherapy.
      The cytokine concentrations were measured using multiplexed cytokine
      immunoassays. The clinical informatics was scored with a Digital Evaluation Score
      System (DESS) to assess the severity of the patients. All patients completed
      follow-up for up to 2 years. RESULTS: Among the 40 mediators measured, 13
      significantly differed between patients with lung cancer and healthy controls,
      while 18 differed between untreated patients and those with stage IV
      adenocarcinoma who had undergone the first and second chemotherapy courses. The
      protein network of cytokines in NSCLC after multiple courses of chemotherapy was
      similar to that of normal persons. MIP-3alpha is the most crucial biomarker for
      predicting survival rates in NSCLC patients. CONCLUSIONS: Our data identify an
      NSCLC-specific profile of inflammatory mediators that may be useful for cancer
      sub-classification, as well as the evaluation of therapeutic effects and overall
      survival.

PMID- 25976769
TI  - Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates
      their cancer stem cell-like phenotype, and reduces doxorubicin-associated
      toxicity.
AB  - Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated
      with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and
      first-line anticancer agent, effective against a wide spectrum of neoplasms
      including breast carcinoma, is associated with several cumulative dose-dependent
      adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity.
      This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC
      cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently
      its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre
      treatment of the TNBC cells with 10 uM Ova 24 h before Doxo administration
      increased the Doxo anticancer effect (IC50 1.4 uM) compared to simultaneous
      treatment with Doxo ( IC50 1.8 uM), or Doxo alone (IC50 9.2 uM). Intracellular
      accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo
      concentrations, when compared with Doxo or simultaneously treated cells. In
      comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells
      treated concurrently with 2.5 uM Ova and 1.25 uM Doxo showed increased percentage
      of cells arrested at G0/G1; however, pre-treatment with the same concentration of
      Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold
      increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis,
      and significantly reduced intracellular Doxo accumulation. Additionally, Ova
      sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced
      by significant dissolution, necrosis of formed mammospheres. Taken together,
      these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates
      doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype. 

PMID- 25976770
TI  - Disease prioritarianism: a flawed principle.
AB  - Disease prioritarianism is a principle that is often implicitly or explicitly
      employed in the realm of healthcare prioritization. This principle states that
      the healthcare system ought to prioritize the treatment of disease before any
      other problem. This article argues that disease prioritarianism ought to be
      rejected. Instead, we should adopt 'the problem-oriented heuristic' when making
      prioritizations in the healthcare system. According to this idea, we ought to
      focus on specific problems and whether or not it is possible and efficient to
      address them with medical means. This has radical implications for the extension
      of the healthcare system. First, getting rid of the binary disease/no-disease
      dichotomy implicit in disease prioritarianism would improve the ability of the
      healthcare system to address chronic conditions and disabilities that often defy
      easy classification. Second, the problem-oriented heuristic could empower medical
      practitioners to address social problems without the need to pathologize these
      conditions. Third, the problem-oriented heuristic clearly states that what we
      choose to treat is a normative consideration. Under this assumption, we can
      engage in a discussion on de-medicalization without distorting preconceptions.
      Fourth, this pragmatic and de-compartmentalizing approach should allow us to
      reconsider the term 'efficiency'. 

PMID- 25976771
TI  - Is delayed reconstruction using the latissimus dorsi free flap a worthy option in
      the management of open IIIB tibial fractures?
AB  - Early reconstruction of severe open fractures, performed within 7 days of the
      injury, has a better outcome than closure after 7 days. However, the uncertain
      demarcation of damaged tissue often results in delayed reconstruction. In this
      article, we report our surgical outcomes of delayed reconstruction using
      latissimus dorsi free flap with internal fixation. Twenty-three patients with
      Gustilo type IIIB open tibial fractures Between March 2009 and May 2012 were
      included in this study. There were 16 cases of distal 1/3 fracture of the tibia,
      4 of midshaft fracture, 1 of proximal 1/3 fracture, and 2 of segmental fracture.
      Serial debridement with application of negative pressure wound therapy (NPWT) was
      performed before the final operation. All patients underwent internal fixation of
      the bone and reconstruction of soft tissue defect using latissimus dorsi free
      flap. The number of serial debridements, excluding those performed during
      emergency and finial operation, ranged from 1 to 5 (mean 2.69) times. Mean time
      from injury to final operation was 10.65 (range, 7-22) days. All flaps survived
      without complications. Three cases (13%) were infected, and three cases required
      further bone graft surgery to facilitate bone union (13%). Bone union was
      achieved after a mean 6.3 (range, 3-12) months. Mean follow-up period was 16.34
      (range, 12-26) months. During follow-up, all patients were able to ambulate
      without use of an aid. In cases of severe open fracture, treatment should
      emphasize soft tissue coverage rather than rushing to achieve definitive fixation
      in the setting of poor surrounding tissues. When delayed reconstruction is
      inevitable, radical debridement is performed first, then NPWT is used as bridging
      therapy, and free flap could be considered for definite soft tissues coverage.
      (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:453-459, 2016. 

PMID- 25976772
TI  - BCR repertoire sequencing: different patterns of B-cell activation after two
      Meningococcal vaccines.
AB  - Next-generation sequencing was used to investigate the B-cell receptor heavy
      chain transcript repertoire of different B-cell subsets (naive, marginal zone
      (MZ), immunoglobulin M (IgM) memory and IgG memory) at baseline, and of plasma
      cells (PCs) 7 days following administration of serogroup ACWY meningococcal
      polysaccharide and protein-polysaccharide conjugate vaccines. Baseline B-cell
      subsets could be distinguished from each other using a small number of repertoire
      properties (clonality, mutation from germline and complementarity-determining
      region 3 (CDR3) length) that were conserved between individuals. However,
      analyzing the CDR3 amino-acid sequence (which is particularly important for
      antigen binding) of the baseline subsets showed few sequences shared between
      individuals. In contrast, day 7 PCs demonstrated nearly 10-fold greater sequence
      sharing between individuals than the baseline subsets, consistent with the PCs
      being induced by the vaccine antigen and sharing specificity for a more limited
      range of epitopes. By annotating PC sequences based on IgG subclass usage and
      mutation, and also comparing them with the sequences of the baseline cell
      subsets, we were able to identify different signatures after the polysaccharide
      and conjugate vaccines. PCs produced after conjugate vaccination were
      predominantly IgG1, and most related to IgG memory cells. In contrast, after
      polysaccharide vaccination, the PCs were predominantly IgG2, less mutated and
      were equally likely to be related to MZ, IgM memory or IgG memory cells. High
      throughput B-cell repertoire sequencing thus provides a unique insight into
      patterns of B-cell activation not possible from more conventional measures of
      immunogenicity. 

PMID- 25976773
TI  - Myocardial Fibrosis and Left Ventricular Dysfunction in Duchenne Muscular
      Dystrophy Carriers Using Cardiac Magnetic Resonance Imaging.
AB  - The goal of our study was to characterize the degree of myocardial fibrosis and
      left ventricular dysfunction in our cohort of Duchenne muscular dystrophy (DMD)
      carriers using cardiac magnetic resonance imaging (CMR). Seventy percent of males
      with DMD have mothers who are carriers of the Xp21 mutation. Carrier phenotypic
      characteristics range from asymptomatic to left ventricular (LV) dysfunction and
      cardiomyopathy. The true prevalence of cardiac involvement in DMD carriers is
      unknown. We performed a retrospective observational study. All female DMD
      carriers who underwent clinical CMR studies at Cincinnati Children's Hospital
      Medical Center from December 6, 2006, to August 28, 2013, were evaluated.
      Patients underwent standard CMR assessment with LV function assessment and late
      gadolinium enhancement (LGE). In addition, offline feature tracking strain
      analysis was performed on the basal, mid, and apical short axis. Twenty-two
      patients were studied, of which 20 underwent adequate testing for myocardial LGE.
      Four of 22 patients (18 %) were found to have LV dysfunction (ejection fraction
      <55 %). Seven of 20 DMD carriers (35 %) were found to have LGE. The patients with
      evidence of LGE had an overall trend to lower absolute deformation parameters;
      however, this did not meet statistical significance when correcting for multiple
      comparisons. Our study demonstrates a high rate of LGE as well as LV dysfunction
      in DMD carriers. Cardiovascular and musculoskeletal symptoms were not
      statistically different between those with and without cardiac involvement. This
      study demonstrates the importance of surveillance CMR evaluation of DMD carriers.

PMID- 25976774
TI  - Individual differences in working memory capacity are reflected in different ERP
      and EEG patterns to task difficulty.
AB  - This study examined whether there are neural markers of individual differences in
      working memory (WM) capacity and whether these differences are only manifest when
      performing a demanding WM task or at all levels of difficulty. Each subject's WM
      capacity was estimated using a modified digit span task prior to participation in
      an N-back task that varied difficulty from 1- to 4-back. While performing the N
      back task, subjects wore scalp electrodes that allowed measurement of both event
      related potentials (ERP) and event-related synchronization and desynchronization
      (ERS/ERD). Those subjects classified as low WM were more affected by the higher
      cognitive demands (many more errors in the 4-back task and generally slower
      responses) than those classified as high WM. These behavioral differences between
      the two groups were also apparent in the neural markers. Specifically, low WM
      subjects, when compared with high WM subjects, produced smaller P300 amplitudes
      and theta ERS, as well as greater alpha ERD at the most difficult level.
      Importantly, the observed differences in electrophysiological responses between
      the two groups were also observed at the lowest difficulty level, not just when
      the task challenged WM capacity. In addition, P300 amplitudes and alpha ERD
      responses were found to correlate with individual WM capacities independent of
      the task difficulty. These results suggest that there are qualitative neural
      differences among individuals with different WM capacities when approaching
      cognitive operations. Individuals with high WM capacities may make more efficient
      use of neural resources to keep their attention focused on the task-relevant
      information when performing cognitive tasks. 

PMID- 25976776
TI  - A 21 Nucleotide Duplication on the alpha1- and alpha2-Globin Genes Involves a
      Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease.
AB  - alpha-Thalassemia (alpha-thal) is a common genetic disorder in Iran and many
      parts of the world. Genetic defects in the alpha-globin gene cluster can result
      in alpha-thal that may develop into a clinical phenotype varying from almost
      asymptomatic to a lethal hemolytic anemia. Loss of one functional alpha gene,
      indicated as heterozygous alpha(+)-thal, shows minor hematological abnormalities.
      Homozygosity for alpha(+)- or heterozygosity for alpha(0)-thal have more severe
      hematological abnormalities due to a markedly reduced alpha chain output. At the
      molecular level, the absence of three alpha-globin genes resulting from the
      compound heterozygous state for alpha(0)- and alpha(+)-thal, lead to Hb H
      disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino
      acids and 3 bp of intronic sequence at the exon-intron boundary, in both the
      alpha-globin genes, detected by direct DNA sequencing. This duplication was
      identified in three patients originating from two different Iranian ethnic groups
      and one Arab during more than 12 years. The clinical presentation of these
      individuals varies widely from a mild asymptomatic anemia (heterozygote in alpha1
      globin gene) to a severely anemic state, diagnosed as an Hb H individual
      requiring blood transfusion (duplication on the alpha2-globin gene in combination
      with the - -(MED) double alpha-globin gene deletion). The third individual, who
      was homozygous for this nt duplication on the alpha1-globin gene, showed severe
      hypochromic microcytic anemia and splenomegaly. In the last decade, numerous
      alpha-globin mutations have demonstrated the necessity of prenatal diagnosis
      (PND) for alpha-thal, and this study has contributed another mutation as
      important enough that needs to be considered. 

PMID- 25976775
TI  - Positive regulation of neocortical synapse formation by the Plexin-D1 receptor.
AB  - Synapse formation is a critical process during neural development and is
      coordinated by multiple signals. Several lines of evidence implicate the Plexin
      D1 receptor in synaptogenesis. Studies have shown that Plexin-D1 signaling is
      involved in synaptic specificity and synapse formation in spinal cord and
      striatum. Expression of Plexin-D1 and its principal neural ligand, Sema3E, by
      neocortical neurons is temporally and spatially regulated, reaching the highest
      level at the time of synaptogenesis in mice. In this study, we examined the
      function of Plexin-D1 in synapse formation by primary neocortical neurons in
      vitro. A novel, automated image analysis method was developed to quantitate
      synapse formation under baseline conditions and with manipulation of Plexin-D1
      levels. shRNA and overexpression manipulations caused opposite changes, with
      reduction resulting in less synapse formation, an effect distinct from that
      reported in the striatum. The data indicate that Plexin-D1 operates in a cell
      context-specific fashion, mediating different synaptogenic outcomes depending
      upon neuron type. 

PMID- 25976777
TI  - Hb Dartmouth (HBA2: c.200T>C): An alpha2-Globin Gene Associated with Hb H Disease
      in One Homozygous Patient.
AB  - Hb H (beta4) disease is caused by deletion or inactivation of three out of four
      alpha-globin genes. A high incidence of Hb H disease has been reported all over
      the world. There is a wide spectrum of phenotypic presentations, from clinically
      asymptomatic to having significant hepatosplenomegaly and requiring occasional or
      even regular blood transfusions, even more severe anemia, Hb Bart's (gamma4)
      hydrops fetalis syndrome that can cause death in the affected fetuses late in
      gestation. We here present a case who was diagnosed with Hb H disease that
      represents a new genotype for this hereditary disorder. Hb Dartmouth is a variant
      caused by a missense mutation at codon 66 of the alpha2-globin gene (HBA2:
      c.200T>C), resulting in the substitution of leucine by proline. We here emphasize
      the importance of this point mutation involving Hb H disease and also the
      necessity for prenatal diagnosis (PND) for those who carry this point mutation in
      the heterozygous state. 

PMID- 25976778
TI  - Evaluation of Mental Health and Physical Pain in Patients with beta-Thalassemia
      Major in Northern Greece.
AB  - beta-Thalassemia major (beta-TM) is a chronic, genetic blood disorder. Patients
      are considered to be vulnerable to emotional and behavioral problems. The aim of
      this study was to assess mental health and somatic pain of patients with
      homozygous beta-TM, who are systematically transfused in our unit. In this
      survey, 54 adult patients were studied. The general health questionnaire (GHQ-28)
      was used as mental health assessment model aimed at detecting mental disorders.
      The model of Binary was used as scoring method of GHQ-28. Overall ratings below 5
      indicate no psychiatric problem, while a total score over or equal to 5 indicated
      the likelihood of a psychiatric disorder. The visual analogue scale (VAS) of pain
      was used as model for pain evaluation. One out of four examined patients who
      presented with a GHQ-28 score above or equal to 5 had an increased chance of
      being diagnosed with a psychiatric disorder. Concerning the pain, the majority of
      the studied patients scored between 1 and 3, meaning that they were feeling mild
      pain. There was no statistical significant correlation between age and GHQ-28
      score. There was a statistical significant correlation between age and somatic
      symptoms (p = 0.026), anxiety and somatic symptoms (0.004) as well as anxiety and
      depression (p = 0.022). Thalassemic patients tend to be diagnosed with
      psychiatric disorders and it seems that they do not feel severe pain. More
      quantitative and comprehensive studies have to be conducted in order to estimate
      specific effective factors in psychosocial health. 

PMID- 25976779
TI  - Fanconi's Anemia Effect or Sickle Cell Anemia Effect: That is the Question.
AB  - A 16-year-old boy who was diagnosed to have sickle cell anemia was referred to
      our center. The parental consanguinity, growth retardation and dysmorphic
      features prompted a search for possible Fanconi's Anemia (FA). The diepoxybutane
      (DEB) test was positive, confirming FA. The interaction of both diseases might
      account for his relatively mild phenotype in terms of both sickle cell anemia (or
      Hb S, HBB: c.20A > T) and FA. The high Hb F level that might be related to
      concomitant FA, may have caused a milder phenotype of sickle cell anemia, whereas
      nitric oxide (NO) depletion as a consequence of sickle cell anemia, may have
      caused a delay in the bone marrow failure of FA.

PMID- 25976780
TI  - Near infrared spectroscopy for frontal lobe oxygenation during non-vascular
      abdominal surgery.
AB  - PURPOSE: Cerebral deoxygenation, as determined by near infrared spectroscopy
      (NIRS), seems to predict postoperative complications following cardiac surgery.
      We identify the type of non-vascular abdominal surgery associated with cerebral
      deoxygenation and/or hyperoxygenation, how such deviations affect patient
      outcome, and whether maintained cerebral oxygenation improves outcome. METHODS: A
      systematic literature search was performed on PubMed, EMBASE, Web of Science and
      Clinicaltrials.gov. RESULTS: A total of 901 patients from 24 publications are
      described. A decrease in NIRS (>15% relative to baseline) manifested with reverse
      Trendelenburg's positioning and in 24% (median) of especially elderly patients
      undergoing open surgery and demonstrated a correlation to hospital stay (LOS).
      However, if cerebral deoxygenation was reversed promptly, improved postoperative
      cognitive function (28 versus 26; mini-mental state examination) and reduced LOS
      (14 versus 23 days) were seen. Also, during liver transplantation (LTx), impaired
      cerebral autoregulation (25%), cerebral deoxygenation in the anhepatic phase
      (36%) and cerebral hyperoxygenation with reperfusion of the grafted liver (14%)
      were identified by NIRS and could lead to adverse neurological outcome, that is
      seizures, transient hemiparesis and stroke. CONCLUSION: NIRS seems important for
      predicting neurological complications associated with LTx. Also, surgery in
      reverse Trendelenburg's position and in other types of abdominal surgery about
      one-fourth of the patients are subjected to episodes of cerebral deoxygenation
      that seems to predict a poor outcome. Although there are currently only few
      studies available for patients going through abdominal surgery, the available
      evidence points to that it is an advantage to maintain the NIRS-determined
      cerebral oxygenation.

PMID- 25976782
TI  - The International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015):
      An introduction.

PMID- 25976781
TI  - Calponin-h2 is upregulated in the tissues and plasma of patients with breast
      cancer.
AB  - Increasing evidence has demonstrated that changes in plasma nuclear matrix
      proteins are specific markers of cancer. Furthermore, proteomic analysis has
      revealed that calponin-h2 is upregulated in human breast cancer tissue, but is
      absent in healthy and benign controls. However, the roles of levels of plasma
      calponin-h2 in the diagnosis of breast cancer and its association with
      clinicopathological parameters remain to be elucidated. In the present study, the
      plasma levels of calponin-h2 in patients with breast cancer, benign breast
      disease and in healthy controls were examined using an enzyme-linked
      immunosorbent assay. The expression levels of calponin-h2 in invasive breast
      cancer and normal breast tissues were measured using immunohistochemistry.
      Statistical analyses examined the association between the levels of plasma
      calponin-h2 and clinicopathological parameters. The results demonstrated that the
      plasma level of calponin-h2 in breast cancer was significantly higher than those
      in the healthy control and benign breast disease groups (P<0.05). The combination
      of calponin-h2, carcinoembryonic antigen, carbohydrate antigen 15-3 improved the
      diagnosis of breast cancer. The plasma levels of calponin-h2 PR-breast cancers
      was significantly higher, compared with PR+ breast cancers (P=0.033), and the
      plasma levels of calponin-h2 in patients with breast cancer aged >50 years was
      significantly higher than in patients <= 50 years of age (P=0.001). No
      association was found between the level of plasma calponin-h2 and other
      clinicopathological parameters of breast cancer. Taken together, these results
      indicated that calponin-h2 may be a useful marker of breast cancer.

PMID- 25976783
TI  - Inhibition of leukocyte-type 12-lipoxygenase by guava tea leaves prevents
      development of atherosclerosis.
AB  - Oxidation of low-density lipoprotein (LDL) is one of the crucial steps for
      atherosclerosis development, and an essential role of leukocyte-type 12
      lipoxygenase expressed in macrophages in this process has been demonstrated. The
      biochemical mechanism of the oxidation of circulating LDL by leukocyte-type 12
      lipoxygenase in macrophages has been proposed. The major ingredients in guava tea
      leaves which inhibited the catalytic activity of leukocyte-type 12-lipoxygenase
      were quercetin and ethyl gallate. Administration of extracts from guava tea
      leaves to apoE-deficient mice significantly attenuated atherogenic lesions in the
      aorta and aortic sinus. We recently showed that Qing Shan Lu Shui inhibited the
      catalytic activity of leukocyte-type 12-lipoxygenase. The major components
      inhibiting the enzyme contained in Qing Shan Lu Shui were identified to be novel
      monoterpene glycosides. The anti-atherogenic effect of the tea leaves might be
      attributed to the inhibition of leukocyte-type 12-lipoxygenase by these
      components. 

PMID- 25976784
TI  - Sea buckthorn seed oil protects against the oxidative stress produced by
      thermally oxidized lipids.
AB  - Thermally oxidized vegetable ghee was fed to the rabbits for 14 days with
      specific doses of sea buckthorn seed oil (SO). The ghee and SO were characterized
      for quality parameters and fatty acid composition using GC-MS. Rabbits serum
      lipid profile, hematology and histology were investigated. Major fatty acids were
      palmitic acid (44%) and oleic acid (46%) in ghee, while SO contains oleic acid
      (56.4%) and linoleic acid (18.7%). Results showed that oxidized vegetable ghee
      increases the serum total cholesterol, LDL-cholesterols, triglycerides and
      decrease the serum glucose. Oxidized ghee produced toxic effects in the liver and
      hematological parameters. Sea buckthorn oil supplementation significantly lowered
      the serum LDL-cholesterols, triglycerides and increased serum glucose and body
      weight of the animals. Sea buckthorn oil was found to reduce the toxic effects
      and degenerative changes in the liver and thus provides protection against the
      thermally oxidized lipids induced oxidative stress.

PMID- 25976786
TI  - Interaction mechanism between green tea extract and human alpha-amylase for
      reducing starch digestion.
AB  - This study evaluated the inhibitory effects of the green tea extract on human
      pancreatic alpha-amylase activity and its molecular mechanism. The green tea
      extract was composed of epicatechin (59.2%), epigallocatechin gallate (14.6%) and
      epicatechin gallate (26.2%) as determined by HPLC analysis. Enzyme activity
      measurement showed that % inhibition and IC50 of the green tea extract (10%,
      based on starch) were 63.5% and 2.07 mg/ml, respectively. The Michaelis-Menten
      constant remained unchanged but the maximal velocity decreased from 0.43
      (control) to 0.07 mg/(ml * min) (4 mg/ml of the green tea extract), indicating
      that the green tea extract was an effective inhibitor against alpha-amylase with
      a non-competitive mode. The fluorescence data revealed that the green tea extract
      bound with alpha-amylase to form a new complex with static quenching mechanism.
      Docking study showed the epicatechin gallate in the green tea extract presented
      stronger affinity than epigallocatechin gallate, with more number of amino acid
      residues involved in amylase binding with hydrogen bonds and Van der Waals
      forces. Thus, the green tea extract could be used to manipulate starch digestion
      for potential health benefits.

PMID- 25976785
TI  - Inhibition effects of Chinese cabbage powder on aflatoxin B1-induced liver
      cancer.
AB  - In this study, 0.25 MUg/ml aflatoxin B1 was used to establish a liver cancer
      model for assessing the potential anticancer ability of Chinese cabbage powder,
      which is a complex water-soluble extract from Chinese cabbage by spray-drying at
      an outlet temperature of 130  degrees C. We found at least 11 potential
      anticancer substances in Chinese cabbage powder. A 90-d animal experiment
      demonstrated that 10% of Chinese cabbage powder in drinking water could improve
      the plasma micronutrient status, inhibit the formation of aflatoxin B1-DNA
      adducts in liver cells, and effectively reduce the incidence of liver tumor
      induced by aflatoxin B1 from 6.67% to 0%. The dose effect experiment revealed
      that 10% may be the minimal effective dose to prevent the occurrence of early
      liver tumors. This study will help elucidate the basis of epidemiological
      observations of dietary cancer prevention in humans, as well as explore related
      mechanisms.

PMID- 25976787
TI  - Water fraction of edible medicinal fern Stenochlaena palustris is a potent alpha
      glucosidase inhibitor with concurrent antioxidant activity.
AB  - This study aimed to isolate a potent antiglucosidase and antioxidant fraction
      from Stenochlaena palustris. Extraction was performed with hexane, chloroform,
      ethyl acetate, methanol, and water. Antiglucosidase, 2,2-diphenyl-1
      picrylhydrazyl (DPPH) scavenging and ferric reducing antioxidant power (FRAP)
      assays found methanol extract (ME) to be the most active. Water fraction (WF) of
      ME was a stronger alpha-glucosidase inhibitor (EC50 2.9 MUg/mL) than quercetin,
      with weak antiamylase activity. WF was a competitive alpha-glucosidase inhibitor.
      DPPH scavenging activity of WF (EC50 7.7 MUg/mL) was weaker than quercetin. WF
      (EC50 364 MUg/mL) was a stronger hydrogen peroxide scavenger than gallic acid
      (EC50 838 MUg/mL) and was equally strong as quercetin in scavenging superoxide.
      WF possessed moderate copper chelating activity. WF was enriched in total
      phenolics (TP) and hydroxycinnamic acids (THC). TP correlated with antioxidant
      activity (R(2) > 0.76). Only THC correlated with antiglucosidase activity (R(2) =
      0.86). Overall, WF demonstrated concurrent, potent antiglucosidase and
      antioxidant activities.

PMID- 25976788
TI  - Investigation of antibacterial mechanism and identification of bacterial protein
      targets mediated by antibacterial medicinal plant extracts.
AB  - In this paper, we investigated the antibacterial mechanism and potential
      therapeutic targets of three antibacterial medicinal plants. Upon treatment with
      the plant extracts, bacterial proteins were extracted and resolved using
      denaturing gel electrophoresis. Differentially-expressed bacterial proteins were
      excised from the gels and subjected to sequence analysis by MALDI TOF-TOF mass
      spectrometry. From our study, seven differentially expressed bacterial proteins
      (triacylglycerol lipase, N-acetylmuramoyl-L-alanine amidase, flagellin, outer
      membrane protein A, stringent starvation protein A, 30S ribosomal protein s1 and
      60 kDa chaperonin) were identified. Additionally, scanning electron microscope
      study indicated morphological damages induced on bacterial cell surfaces. To the
      best of our knowledge, this represents the first time these bacterial proteins
      are being reported, following treatments with the antibacterial plant extracts.
      Further studies in this direction could lead to the detailed understanding of
      their inhibition mechanism and discovery of target-specific antibacterial agents.

PMID- 25976789
TI  - Bioactivities of phytochemicals in Araiostegia yunnanensis (Christ).
AB  - The profile and bioactivity of phytochemicals in Araiostegia yunnanensis (Christ)
      Cop were investigated. The total flavonoids content in A. yunnanensis is about
      84.90 mg/g. By means of HPLC-DAD-ESI-MS, the main flavonoids in A. yunnanensis
      were tentatively identified as myricetin 3-O-rhamnosylglucoside, eriodictyol 7-O
      rutinoside, quercetin 3-O-rutinoside, luteolin-7-O-apiosylglucoside, quercetin 3
      O-rhamnosylgalactoside, and luteolin 7-O-glucoside. The extract (0.268 mg/ml
      total flavonoids) from A. yunnanensis showed very strong superoxide anion radical
      scavenging potential and reducing power, which are higher than those of rutin
      (0.25 mg/ml). The extract (0.268 mg/ml total flavonoids) from A. yunnanensis
      exhibited similar DPPH scavenging activity with rutin (0.25 mg/ml). However,
      rutin (0.25 mg/ml) showed a significantly higher ABTS radical scavenging effect
      than that of the extract (0.268 mg/ml total flavonoids) from A. yunnanensis. The
      methanol extract from A. yunnanensis showed obviously cytotoxic effects on A549
      cells and it had no effect against acetylcholinesterase.

PMID- 25976790
TI  - Role of plant polyphenols in acrylamide formation and elimination.
AB  - Acrylamide found in thermal-treated foods has led to an intensive and persistent
      research effort, since it is a neurotoxic, genotoxic and probable carcinogenic
      compound to humans. Plant polyphenols are the most abundant antioxidants in human
      diet. Several researches indicated that the polyphenols affected the acrylamide
      formation during heating. However, the controversial effects of the polyphenols
      on acrylamide formation were related to their structure, concentrations, and
      antioxidant capacity, as well as reaction condition. Polyphenols can inhibit
      acrylamide formation through trapping of carbonyl compounds and preventing
      against lipid oxidation, while some special polyphenols can enhance the
      acrylamide content by providing carbonyl groups, accelerating the conversion from
      3-aminopropionamide (3-APA) to acrylamide and inhibiting acrylamide elimination.
      This review concludes the effects of polyphenols in the Maillard reaction and
      food systems conducted so far, aimed to give an overview on the role of plant
      polyphenols in acrylamide formation and elimination. 

PMID- 25976791
TI  - Phenolic contents and cellular antioxidant activity of Chinese hawthorn
      "Crataegus pinnatifida".
AB  - It is evident from various epidemiological studies that consumption of fruits and
      vegetables is essential to maintain health and in the disease prevention. Present
      study was designed to examine phenolic contents and antioxidant properties of
      three varieties of Crataegus pinnatifida (Chinese hawthorn). Shanlihong variety
      exhibited elevated levels of total phenolics and flavonoid contents, including
      free and bond phenolics. Procyanidin B2 was most abundant phenolic compound in
      all samples, followed by epicatechin, chlorogenic acid, hyperoside, and
      isoquercitrin. The free ORAC values, and free hydro-PSC values were 398.3-555.8
      MUmol TE/g DW, and 299.1-370.9 MUmol VCE/g DW, respectively. Moreover, the free
      cellular antioxidant activity (CAA) values were 678-1200 MUmol of QE/100 g DW in
      the no PBS wash protocol, and 345.9-532.9 MUmol of QE/100 g DW in the PBS wash
      protocol. C. pinnatifida fruit could be valuable to promote consumer health.

PMID- 25976792
TI  - Antioxidant homoisoflavonoids from Polygonatum odoratum.
AB  - Polygonatum odoratum is widely used as a traditional food supplement and herbal
      medicine with strong antioxidant activity. However, systematic investigation of
      its antioxidants was limited. Ethanol extract of P. odoratum was fractioned on
      macroporous absorptive resin (D101) column. A bioassay-guided purification of
      flavonoid-rich fraction (IC50 value at 74.1 +/- 11.9 MUg/mL for DPPH scavenging)
      was realised via high-speed counter-current chromatography (HSCCC) using
      petroleum ether-ethyl acetate-methanol-water (2:3:3:2, v/v/v/v) as the solvent
      system combination with Sephadex LH-20 column chromatography (CC) eluting with
      MeCN-MeOH (1:1, v/v). Three novel homoisoflavonoids (1-3), along with eight
      homoisoflavonoids (4-11), were isolated. Their structures were elucidated by
      interpretating various spectroscopic data. All the isolated homoisoflavonoids
      showed potent antioxidant activities, while compounds 1, 4, and 6 with
      dihydroxylated B-rings exhibited stronger antioxidant activities (IC50 values at
      3.8 +/- 0.5, 4.9 +/- 0.3 and 3.9 +/- 0.4 MUg/mL) than ascorbic acid (IC50 value
      at 5.3 +/- 0.6 MUg/mL).

PMID- 25976793
TI  - Effect of cultivar and variety on phenolic compounds and antioxidant activity of
      cherry wine.
AB  - To compare the influence of cultivar and variety on the phenolic compounds and
      antioxidant activity (AA) of cherry wines, total phenolic (TP), total flavonoid
      (TF), total anthocyanin (TA), total tannin (TT), five individual phenolic acids,
      and AA were determined. An ultra-performance liquid chromatography tandem mass
      spectrometry (HPLC-DAD/ESI-MS) method was developed for the determination of
      gallic acid (GAE), p-hydroxybenzoic acid (PHB), chlorogenic acid (CHL), vanillic
      acid (VAN), and caffeic acid (CAF). A principal component analysis (PCA) and a
      cluster analysis (CA) were used to analyze differences related to cultivar and
      variety. The TP, TF, TA, TT, and AA of samples sourced from the Shandong province
      of China were higher than those from the Jiangsu province. The PCA and CA results
      showed that phenolic compounds in cherry wines were closely related to cultivar
      and variety and that cultivar had more influence on the phenolic compounds of
      cherry wines than variety. 

PMID- 25976794
TI  - Influence of different processing and storage conditions on in vitro
      bioaccessibility of polyphenols in black carrot jams and marmalades.
AB  - Black carrot is indicated to play an important role in nutrition, as it comprises
      a variety of health-promoting components, including polyphenols. The objective of
      the present study was to monitor the stability of total phenolics, antioxidant
      capacity and phenolic acids in black carrot jams and marmalades after processing,
      storage and in vitro gastrointestinal digestion. Total phenolic content and
      antioxidant capacity were determined using spectrophotometric methods, whereas
      phenolic acids were identified using HPLC-PDA. Jam and marmalade processing
      significantly decreased total phenolics (89.2-90.5%), antioxidant capacity (83.3
      91.3%) and phenolic acids (49.5-96.7%) (p < 0.05). After 20 weeks of storage, the
      percent decrease in total phenolics in samples stored at 25  degrees C (26.4
      48.0%) was slightly higher than the samples stored at 4  degrees C (21.0-42.5%).
      In addition, jam and marmalade processing led to increases in the percent
      recovery of bioaccessible total phenolics (7.2-12.6%) and phenolic acids (4.7
      31.5%), as well as antioxidant capacity (1.4-8.1%). In conclusion, current study
      highlighted black carrot jams and marmalades as good sources of polyphenols, with
      high bioaccessibility levels.

PMID- 25976795
TI  - Characterisation of polyphenol constituents of Linderae aggregate leaves using
      HPLC fingerprint analysis and their antioxidant activities.
AB  - The leaves of Linderae aggregate (LAL) has been used as a type of tea in China
      and other Southeast Asian countries. In this study, 11 polyphenols in LAL were
      clarified for the first time using multiple high-performance liquid
      chromatographic techniques. An optimal extracting method was developed through
      the comparison of the amount of quercetin-3-O-alpha-L-rhamnoside using a uniform
      design method. From the fingerprint liquid chromatography data, 11 common peaks
      in the 8 samples collected from April to November were semi-determined. The
      antioxidant capacities were examined using the 2,2-diphenyl-1-picrylhydrazyl free
      radical scavenging assay and the ferric reducing/antioxidant power assay. All 8
      samples contained the same 11 polyphenols in similar ratios. Three samples, S2,
      S5 and S6 contained higher amount of quercetin-3-O-alpha-L-rhamnoside and were
      demonstrated to have stronger antioxidant capacities in both antioxidant assays.
      These results are critical in optimising harvest time and quality control of LAL.

PMID- 25976796
TI  - Characterisation and stability of anthocyanins in purple-fleshed sweet potato
      P40.
AB  - Purple-fleshed sweet potato P40 has been shown to prevent colorectal cancer in a
      murine model. This study is to identify anthocyanins by using HPLC/MS-MS and
      assess the stability during various cooking conditions. P40 possesses a high
      content of anthocyanins up to 14 mg/g dry matter. Total 12 acylated anthocyanins
      are identified. Top three anthocyanins, e.g., cyanidin 3-caffeoyl-p
      hydroxybenzoyl sophoroside-5-glucoside, peonidin 3-caffeoyl sophoroside-5
      glucoside, and cyanidin 3-(6"-caffeoyl-6"-feruloylsophoroside)-5-glucoside,
      account for half of the anthocyanin contents. Over 80% of anthocyanins measured
      by acid hydrolysis were cyanidin derivatives, indicating P40 is unique when
      compared with other purple-fleshed sweet potatoes that usually contain more
      peonidin than cyanidin. Steaming, pressure cooking, microwaving, and frying but
      not baking significantly reduced 8-16% of total anthocyanin contents. Mono
      acylated anthocyanins showed a higher resistance against heat than di- and non
      acylated. Among of which, cyanidin 3-p-hydroxybenzoylsophoroside-5-glucoside
      exhibited the best thermal stability. The stable acylated and cyanidin
      predominated anthocyanins in P40 may provide extra benefits for cancer
      prevention.

PMID- 25976797
TI  - Extraction, chemical composition and antioxidant activity of flavonoids from
      Cyclocarya paliurus (Batal.) Iljinskaja leaves.
AB  - Microwave-assisted extraction of flavonoids from Cyclocarya paliurus (Batal.)
      Iljinskaja leaves, its chemical composition and antioxidant activity were
      investigated in this study. The influences of parameters including temperature,
      extraction time, ratio of material to solvent and solvents on the yield of
      flavonoids were studied. The optimal conditions were determined and the quadratic
      response surfaces were drawn from the mathematical models. The maximum extraction
      yield of 15.64 mg/g was achieved at temperature of 76.8  degrees C, extraction
      time of 15 min, alcohol concentration of 63.2% and ratio of solvent to material
      of 21.4:1. Five main constituents in the extract including quercetin-3-O-beta-D
      glucuronide, quercetin, kaempferol-3-O-beta-D-glucuronide, kaempferol-7-O-alpha-L
      rhamnoside and kaempferol were identified by LC-MS. In vitro antioxidant assays
      showed that the extract exhibited a strong DPPH radical-scavenging ability with
      IC50 value of 0.146 mg/mL. Results indicated that MAE was a suitable approach for
      the selective extraction of flavonoids from C. paliurus (Batal.) Iljinskaja
      leaves.

PMID- 25976798
TI  - Type 2 diabetes diminishes the benefits of dietary antioxidants: Evidence from
      the different free radical scavenging potential.
AB  - The development of food fortified with polyphenols and polyphenol-rich foods
      represents a novel approach for preventing or managing type 2 diabetes. Herein,
      taking advantage of several radical scavenging, the impact of plasma proteins in
      diabetes on the benefits of dietary polyphenols was investigated. It illustrated
      that plasma proteins masked the dietary polyphenols, thus reducing their radical
      scavenging potential. The plasma proteins from type 2 diabetics bind and protect
      (i.e., mask) the polyphenol antioxidants less effectively than the non
      glycosylated ones in healthy blood do. In the blood of diabetics the less
      protected (non-masked) antioxidants react with free radicals before being
      delivered to the tissues that need them. We should pay more attention to in vivo
      benefits of dietary polyphenols for type 2 diabetics. 

PMID- 25976799
TI  - Seasonal dynamics of total flavonoid contents and antioxidant activity of
      Dryopteris erythrosora.
AB  - The seasonal dynamics of the total flavonoid contents in various parts of
      Dryopteris erythrosora, a traditional Chinese medicinal fern, and their
      antioxidant activity were investigated. The total flavonoids content in various
      parts of D. erythrosora showed an obvious seasonal dynamic change. The total
      flavonoid contents in stems (from 4.3% to 12.5%) were much higher than that in
      leaves with an average content of 2.01%. In spring, the total flavonoid contents
      in stems were relatively low, but increased rapidly from summer to winter.
      However, the seasonal dynamics of total flavonoid contents in leaves showed
      different model. The total flavonoid contents in the stems showed a negative
      correlation with that in the leaves from January to July. The correlation
      coefficient of about -0.7 was obtained. The antioxidant activity of the extracts
      also altered in proportion to the change of total flavonoid contents. In general,
      the extracts from stems always showed highest antioxidant potentials and it was
      suggested that the stems can be used as crude medicine. 

PMID- 25976800
TI  - Isolation, purification and identification of etiolation substrate from fresh-cut
      Chinese water-chestnut (Eleocharis tuberosa).
AB  - Fresh cut Chinese water-chestnut is a popular ready-to-eat fresh-cut fruit in
      China. However, it is prone to etiolation and the chemicals responsible for this
      process are not known yet. To address this problem, we extracted phytochemicals
      from etiolated Chinese water-chestnut and separated them using MPLC and column
      chromatography. Four compounds were obtained and their structures were determined
      by interpretation of UV, TLC, HPLC and NMR spectral data and by comparison with
      reported data. We identified these compounds as eriodictyol, naringenin, sucrose
      and ethyl D-glucoside. Among those, eriodictyol and naringenin were both isolated
      for the first time in fresh-cut Chinese water-chestnut and are responsible for
      the yellowing of this fruit cutting.

PMID- 25976801
TI  - Metabolic profiling of antioxidants constituents in Artemisia selengensis leaves.
AB  - This study aimed to evaluate the antioxidant potential of Artemisia selengensis
      Turcz (AST) leaves, a byproduct when processing AST stalk, and identify the
      antioxidant constituents by using HPLC-QTOF-MS(2). The total phenolics content
      (TPC), total flavonoids content (TFC) and antioxidant abilities of fractions
      resulted from the successively partition of chloroform, ethyl acetate and n
      butanol were compared. Ethyl acetate fraction (EAF) exhibited the highest TFC
      (65.44 mg QuE/g fraction), n-butanol fraction (nBuF) showed the highest TPC
      (384.78 mg GAE/g fraction) and the best DPPH scavenging ability, ABTS(+)
      scavenging ability and reducing power. Totally, 57 compounds were identified or
      tentatively identified in nBuF and EAF, 40 of them were reported in AST for the
      first time. The major constituents in EAF were flavonoids, and the major
      constituents in nBuF were phenolic acids and organic acids. Thus, AST leaves
      might be a potential low-cost resource of natural antioxidants.

PMID- 25976802
TI  - Bioactivity-guided isolation of antimicrobial coumarins from Heracleum
      mantegazzianum Sommier & Levier (Apiaceae) fruits by high-performance counter
      current chromatography.
AB  - An efficient strategy, based on bioassay-guided fractionation, high-performance
      liquid chromatography (HPLC), and high-performance counter-current chromatography
      (HPCCC), was established to purify and evaluate the bioactive compounds from the
      dichloromethane extract of the fruits of Heracleum mantegazzianum Sommier &
      Levier (Apiaceae). The quaternary solvent system n-heptane-ethyl acetate-methanol
      water (6:5:6:5 v/v) was used in the reversed phase mode. Using this method, in a
      single run, seven fractions were isolated, among them three were the pure
      furanocoumarins: pimpinellin, imperatorin, and phellopterin. In order to purify
      xanthotoxin a more polar system (1:1:1:1 v/v) was further applied. The
      antimicrobial activity of extract, chromatographic fractions, and single
      compounds were in the range of MIC = 0.03-1 mg mL(-1). Xanthotoxin may have
      priority as a compound of further interest based on its antimicrobial activity.
      For the first time, an extensive antimicrobial study was performed for
      pimpinellin and phellopterin.

PMID- 25976803
TI  - Separation of polyphenols from leaves of Malus hupehensis (Pamp.) Rehder by off
      line two-dimensional High Speed Counter-Current Chromatography combined with
      recycling elution mode.
AB  - In this study, off-line two-dimensional High Speed Counter-Current Chromatography
      (2D HSCCC) strategy combined with recycling elution mode was developed to isolate
      compounds from the ethyl acetate extract of a common green tea--leaves of Malus
      hupehensis (Pamp.) Rehder. In the orthogonal separation system, a conventional
      HSCCC was employed for the first dimension and two recycling HSCCCs were used for
      the second in parallel. Using a solvent system consisting of n-hexane-ethyl
      acetate-methanol-water (1:4:0.6:4.4, v/v) in the first and second dimension, four
      compounds including 3-hydroxy-phlorizin (1), phloretin (2), avicularin (3) and
      kaempferol 3-O-beta-D-glucoside (4) were obtained. The purities of these four
      compounds were all over 95.0% as determined by HPLC. And their structures were
      all identified through UV, MS and (1)H NMR. It has been demonstrated that the
      combination of off-line 2D HSCCC with recycling elution mode is an efficient
      technique to isolate compounds with similar polarities in natural products.

PMID- 25976804
TI  - Purification of six lignans from the stems of Schisandra chinensis by using high
      speed counter-current chromatography combined with preparative high-performance
      liquid chromatography.
AB  - A method for the preparative purification of lignans from Schisandra chinensis
      was established using a combination of high-speed counter-current chromatography
      (HSCCC) and preparative high-performance liquid chromatography (HPLC). The crude
      extracts obtained from S. chinensis by using 70% ethanol were separated on a
      macroporous resin column and then eluted with a graded ethanol series. A two
      phase solvent system consisting of n-hexane-ethyl acetate-methanol-water
      (1:1:1:1, v/v) was used for HSCCC, and a mobile phase of acetonitrile-water
      (50:50, v/v) was used for preparative HPLC. The results obtained using HSCCC were
      compared with those obtained using preparative HPLC, and their advantages were
      further integrated to improve the separation efficiency. Six known lignans were
      identified by electrospray ionisation mass spectrometry and (1)H nuclear magnetic
      resonance (NMR) and (13)C NMR analyses; the purities of all the compounds were
      more than 91%. 

PMID- 25976805
TI  - Separation of five flavonoids from tartary buckwheat (Fagopyrum tataricum (L.)
      Gaertn) grains via off-line two dimensional high-speed counter-current
      chromatography.
AB  - An off-line two dimensional (2D) high-speed counter-current chromatography
      (HSCCC) strategy was successfully used for preparative separation of five
      flavonoids from tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) grains with
      different solvent systems for the first time in this paper. n-Hexane-ethyl
      acetate-methanol-water 3:5:3:5 (v/v) was selected as the first dimension solvent
      system to purify quercetin (4) and kaempferol (5). The second dimension solvent
      system, ethyl acetate-n-butanol-water 7:3:10 (v/v), was used to isolate quercetin
      3-O-rutinoside-3'-O-beta-glucopyranoside (1), rutin (2) and kaempferol 3
      rutinoside (3). The purities of these compounds were all above 96.0% and their
      structures were identified through UV, MS and (1)H NMR. The results indicated
      that the off-line 2D HSCCC is an efficient technique to isolate flavonoids
      compounds from grains. 

PMID- 25976806
TI  - New steroidal saponin and antiulcer activity from Solanum paniculatum L.
AB  - Solanum paniculatum L. (Solanaceae) is a plant species widespread throughout
      tropical America, especially in the Brazilian Savanna region. It is used in
      Brazil for culinary purposes and in folk medicine to treat liver and gastric
      dysfunctions, as well as hangovers. Fractionation of the ethanolic extracts (70%)
      from aerial parts (leaves and twigs) of S. paniculatum led to the isolation of
      the two new saponins (22R, 23S, 25R)-3beta, 6alpha, 23-trihydroxy-5alpha
      spirostane 6-O-beta-D-xylopyranosyl-(1"" -> 3"')-O-[beta-D-quinovopyranosyl(1"' 
      > 2')]-O-[alpha-L-rhamnopyranosyl(1" -> 3')]-O-beta-D-quinovopyranoside (1) and
      diosgenin 3-O-beta-D-glucopyranosyl(1" -> 6')-O-beta-D-glucopyranoside (2)
      together with four know compounds: caffeic acid (3), diosgenin beta-D
      glucopyranoside (4), rutin (5), and quercetin 3-O-alpha-L-rhamnopyranosyl (1"' ->
      6 ")-O-beta-D-galactopyranoside (6). The structures of these compounds were
      elucidated by extensive use of 1D and 2D NMR experiments along with HRESIMS
      analyses. Different doses (31.25-500 mg/kg) of ethanolic extract of leaves from
      S. paniculatum were evaluated against gastric ulcer induced by ethanol in rats.
      The lower dose of extract able to promote antiulcer effect was 125 mg/kg. The
      treatment with S. paniculatum by oral route was able to decrease gastric lesion
      area and also reduced levels of myeloperoxidase (MPO) in the gastric mucosa. Our
      results reveal for the first time, steroidal saponins from S. paniculatum and the
      antiulcer effect of this species at this lower dose.

PMID- 25976807
TI  - Comparison of physicochemical characteristics, sensory properties and volatile
      composition between commercial and New Zealand made wakame from Undaria
      pinnatifida.
AB  - This study aims to obtain chemical and sensory profiles of the New Zealand wakame
      from Undaria pinnatifida for the first time since the lift of its commercial
      harvest in May 2010. We compared mannitol content, sensory quality and volatile
      profiles of wakame produced from New Zealand U. pinnatifida with Japanese and
      Korean commercial samples. Sensory analysis showed that New Zealand wakame
      processed in August was different from commercially available wakame in texture
      only. A total of 10 alkanes, 5 ester, 3 alcohol, 13 aldehyde, 8 ketone and 2
      alkyne were detected in the two New Zealand processed wakame samples. Mannitol
      content in freeze-dried U. pinnatifida was also measured and result showed that
      mannitol was the only free carbohydrate in U. pinnatifida. 

PMID- 25976808
TI  - Investigation on biochemical compositional changes during the microbial
      fermentation process of Fu brick tea by LC-MS based metabolomics.
AB  - Fu brick tea (FBT) is a unique post-fermented tea product which is fermented with
      fungi during the manufacturing process. In this study, we investigated the
      biochemical compositional changes occurring during the microbial fermentation
      process (MFP) of FBT based on non-targeted LC-MS, which was a comprehensive and
      unbiased methodology. Our data analysis took a two-phase approach: (1) comparison
      of FBT with other tea products using PCA analysis to exhibit the characteristic
      effect of MFP on the formation of Fu brick tea and (2) comparison of tea samples
      throughout the MFP of FBT to elucidate the possible key metabolic pathways
      produced by the fungi. Non-targeted LC-MS analysis clearly distinguished FBT with
      other tea samples and highlighted some interesting metabolic pathways during the
      MFP including B ring fission catechin. Our study demonstrated that those fungi
      had a significant influence on the biochemical profiles in the FBT and
      consequently contributed to its unique quality. 

PMID- 25976809
TI  - Analysis of bioactivities and chemical composition of Ziziphus joazeiro Mart.
      using HPLC-DAD.
AB  - The aim of this study was to evaluate the chemical profile and antioxidant,
      antimicrobial and antiparasitic activities of the hydroalcoholic extract of the
      leaves of Ziziphus joazeiro Mart. (HELZJ). The antioxidant DPPH and FRAP assays
      and chemical profile were determined by colorimetric methods and HPLC/DAD. The
      antiparasitic, antibiotic and antibiotic-modifying activity were evaluated by
      microdilution assays. The HPLC-DAD assay showed the presence of mostly tannins
      and flavonoids, such as caffeic acid and quercetin. The levels of polyphenols and
      flavonoids were 183.136 mg/g extract and 7.37 mg/g extract, respectively. DPPH
      and FRAP showed low antioxidant activity for the extract. The antibacterial and
      antifungal activities were not of clinical relevance, showing MIC>1024 MUg/mL.
      However, synergism was observed between HELZJ and the antibiotics amikacin and
      gentamicin, which resulted in decreased bacterial drug resistance. EHFZJ showed
      low toxicity in fibroblasts in vitro, while antiparasitic results against
      Trypnosoma cruzi, Leishmania braziliensis and Leishmania infantum were not
      clinically relevant. Thus, our results indicate that Z. joazeiro Mart. (HELZJ)
      could be a source of plant-derived natural products that could lead to the
      development of promising new antibiotic compounds for infectious diseases.

PMID- 25976811
TI  - Distinguishing Radix Angelica sinensis from different regions by HS-SFME/GC-MS.
AB  - An automated headspace solvent free microextraction (HS-SFME) based gas
      chromatography/mass spectrometry (GC/MS) was developed for discrimination of
      Radix Angelica sinensis (RAS) from different cultivation regions. The MS data
      were subjected to principal component analysis (PCA) and hierarchical clustering
      analysis (HCA) to rapidly find the potential characteristic components of RAS
      from top-geoherb region and non top-geoherb region. Totally, fifty-one volatile
      organic compounds (VOCs) were identified, in which beta-ocimene, alpha-pinene, 3
      methylbutanal, heptanes, butanal were identified as potential markers for
      distinguishing RAS from top-geoherb region and non top-geoherb region. Sulphur
      dioxide was detected in some commercial RAS samples, which implied that sulphur
      fumigation might be the main reason for the quality inconsistencies of commercial
      RAS samples. These results suggested that RAS from top-geoherb region and non-top
      geoherb region could be discriminated by the method. And characteristic chemical
      markers found in current study can be used for ensuring consistent quality of top
      geoherb of RAS. 

PMID- 25976810
TI  - Chemical features of Pericarpium Citri Reticulatae and Pericarpium Citri
      Reticulatae Viride revealed by GC-MS metabolomics analysis.
AB  - This paper introduces a detailed method to apply metabolic profiles conducting on
      tangerine peels (Citrus reticulata 'Dahongpao') at three maturity stages from
      July to December. Principal component analysis not only demonstrated the
      metabolic footprints of tangerine peels during ripening but also revealed the
      compounds (D-limonene and linalool) that mostly contributed to it. Furthermore,
      some other characteristic compounds were screened to further reveal the chemical
      features of Pericarpium Citri Reticulatae (PCR) and Pericarpium Citri Reticulatae
      Viride (PCRV). In particular, compounds such as 4-carene (r = -0.94), 3-carene (r
      = -0.91), beta-pinene (r = -0.85) and gamma-terpinene (r = -0.87) were screened
      as major components for the pungent smell of PCRV. Geranyl acetate (r = 0.81),
      farnesyl acetate (r = 0.87) and three alcohols (6-hepten-1-ol, 3-methyl-1
      hexanol, 1-octanol) may lead to the pleasant odour of PCR. We therefore propose
      that the metabolomics analysis focusing on ripening process will be an effective
      strategy for quality control of closely related herbal medicines.

PMID- 25976812
TI  - Advance on the bioactivity and potential applications of dietary fibre from grape
      pomace.
AB  - The winemaking grape pomaces are rich in bioactive phytochemicals and dietary
      fibre (DF). DFs are phenolic-rich DF matrix and are dietary supplement with
      benefits on human health. As a result of the increased attention to
      sustainability of winemaking by-products, efforts have been made to use grape
      pomace in different bio-industries. In this review, we summarize the existing
      knowledge on the bioactivity and potential applications of DF from grape pomace,
      as well as the chemical compositions of DF. Furthermore, the biological
      activities of DF such as, anti-cancer activity, antibacterial activity, anti
      inflammatory activity, antioxidant activity, improving gastrointestinal health
      activity, anti-apoptotic activity, preventing cardiovascular disease activity,
      anti-hypercholesterolemic activity, are discussed. Finally, the possible
      applications and future prospects of grape pomace DF in various fields are also
      summarised. 

PMID- 25976813
TI  - Structural characteristics and physicochemical properties of lotus seed resistant
      starch prepared by different methods.
AB  - Lotus seed resistant starch (LRS) is commonly known as resistant starch type 3
      (LRS3). The objective of this study was to investigate the effect of different
      preparation methods on the structural characteristics and physicochemical
      properties of LRS3. The molar mass of LRS3 prepared by autoclaving method (GP
      LRS3) and ultrasonic-autoclaving method (UP-LRS3) was mainly distributed in the
      range 1.0 * 10(4)-2 * 10(4) g/mol while a decrease of LRS3 prepared by microwave
      moisture method (MP-LRS3) was observed. The particle of MP-LRS3 was smaller and
      relatively smoother while UP-LRS3 was bigger and rougher compared to GP-LRS3.
      Among these samples, GP-LRS3 exhibited the highest degree of ordered structure
      and crystallinity, the amorphous region of MP-LRS3 was the biggest and UP-LRS3
      displayed the highest degree of double helical structure. Additionally, MP-LRS3
      displayed the strongest solubility and swelling power while UP-LRS3 exhibited the
      strongest iodine absorption ability and thermostability, which were affected by
      their structural characteristics.

PMID- 25976815
TI  - Sulfated modification of the polysaccharides from Ganoderma atrum and their
      antioxidant and immunomodulating activities.
AB  - In this study, three chemically sulfated polysaccharides (S-PSG) with different
      degree of sulfate substitution (DS) were derived from Ganoderma atrum. FT-IR and
      (13)C NMR spectra indicated that the substitution was predominantly on C-6
      position compared with the C-2 position. The antioxidant and immunomodulatory
      activities of S-PSG were further examined to determine the relationship between
      its structure and bioactivity. The results showed that compared with the native
      polysaccharide, the S-PSG-2 with moderate DS and molecular weight exhibited the
      highest immunomodulatory activity by increasing the macrophage phagocytosis
      capacity and TNF-alpha production. The DPPH radical scavenging activity was also
      greatly enhanced by S-PSG in all the groups compared with PSG. However, the
      reducing power and the antioxidant activities in beta-carotene-linoleic acid
      assay were decreased. These results indicated that except for the DS, some other
      structural characteristics such as molecular weight, substitution position and
      chain conformation were also important factors affecting their bioactivities. And
      the S-PSG-2 we derived could be served as immunomodulator and free-radical
      inhibitors. 

PMID- 25976814
TI  - Structural and physicochemical properties of lotus seed starch treated with ultra
      high pressure.
AB  - Aqueous lotus seed starch suspensions (15%, w/w) were subjected to ultra-high
      pressure treatment (UHP, 100-600 MPa) for 30 min. The effects of UHP treatment on
      the structural and physicochemical properties of starch were investigated. The
      SEM and laser diffraction particle size analysis revealed that UHP treatment
      affected the shape and size distribution of starch granules. The morphological
      structure of starch was completely destroyed at 600 MPa, indicating complete
      gelatinization. Analysis of HPSEC-MALLS-RI suggested that the dispersity index of
      UHP-treated starch were decreased from 1.28 to 1.11. According to XRD analyses,
      UHP treatment converted native starch (C-type) into a B-type pattern. The
      swelling power and solubility presented a significant decrease at 85 and 95 
      degrees C, but opposite trends were found at 55-75  degrees C. The DSC results
      indicated a reduction in gelatinization temperatures and enthalpy with increasing
      pressure treatment. The RVA viscograms revealed that UHP-treated starch showed a
      decreased breakdown and setback viscosity, reflecting lower retrogradation
      tendency compared to native starch.

PMID- 25976816
TI  - Effect of hemicellulose from rice bran on low fat meatballs chemical and
      functional properties.
AB  - The paper study the functional properties of hemicellulose B (RBHB) and rice bran
      insoluble dietary fibre (RBDF) to develop an acceptable low fat meat product
      enriched with high content fibre from defatted rice bran. Meatballs were produced
      with three different formulations including 2%, 4% and 6% RBHB or RBDF addition.
      The total trans fatty acids were lower and the ratio of total unsaturated fatty
      acids to total saturated fatty acids was higher in the samples with added RBHB
      than in the control meatballs. Meatballs containing RBHB had lower concentrations
      of total fat and total trans fatty acids than the control samples. Sensory
      evaluations revealed that meatballs with 2%, 4% and 6% RBHB were overall
      acceptable. This confirms that the RBHB preparation from defatted rice bran has
      great potential in food applications, especially in development of functional
      foods including functional meat products. 

PMID- 25976817
TI  - Evolution of nutrient ingredients in tartary buckwheat seeds during germination.
AB  - Evolution of nutrient components and the antioxidative activity of seed sprouts
      of tartary buckwheat (Fagopyrum tataricum L. Gaertn) were investigated in the
      course of germination. Results showed that the contents of total flavonoids
      increased with germination time and leveled off after the third germination day
      with the changing trend of rutin and quercetin opposite to each other. The
      decrease of total protein and total sugar contents in the germinated seeds was
      accompanied respectively by an increase of amino acid and reducing sugar
      contents. The contents of vitamin C (Vc) and B1(V(B1)) exhibited a minimum with
      no appreciable changes found for vitamin B(2) (V(B2)) and B(6) (V(B6)). The
      contents of total chlorophyll, chlorophyll A and B all exhibited a maximum on the
      fifth germination day. The contents of fatty acids had no regular changing trend
      with germination time. The free radical-scavenging activities of the seeds
      increased with germination time and were caused by an increase in their
      antioxidative activity.

PMID- 25976818
TI  - Effect of the treatment by slightly acidic electrolyzed water on the accumulation
      of gamma-aminobutyric acid in germinated brown millet.
AB  - The accumulation of gamma-aminobutyric acid and the microbial decontamination are
      concerned increasingly in the production of sprouts. In this work, the effect of
      the treatment by slightly acidic electrolyzed water on the accumulation of gamma
      aminobutyric acid in the germinated brown millet was evaluated by high
      performance liquid chromatography during germination. The results showed that
      slightly acidic electrolyzed water with appropriate available chlorine (15 or 30
      mg/L) could promote the accumulation of gamma-aminobutyric acid by up to 21% (P <
      0.05). However, the treatment with slightly acidic electrolyzed water could not
      enhance the sprouts growth of the germinated brown millet. The catalase and
      peroxidase activities of the germinated brown millet during germination were in
      agreement with the sprouts growth. Our results suggested that the accumulation of
      gamma-aminobutyric acid was independent of the length of sprouts in germinated
      grains. Moreover, the treatment with slightly acidic electrolyzed water
      significantly reduced the microbial counts in the germinated millet (P < 0.05)
      and the treatment with high available chlorine concentration (15 and 30 mg/L)
      showed stronger anti-infection potential in the germinated brown millet than that
      of lower available chlorine concentration (5 mg/L). In conclusion, the treatment
      with slightly acidic electrolyzed water is an available approach to improve the
      accumulation of gamma-aminobutyric acid and anti-infection potential in the
      germinated brown millet, and it can avoid too long millet sprouts.

PMID- 25976819
TI  - Effect of Monascus aged vinegar on isoflavone conversion in soy germ by soaking
      treatment.
AB  - Soy germ rich in isoflavones has attracted much attention for health-promoting
      characteristics. An effective approach via Monascus aged vinegar soaking was
      adopted to enhance the aglycone amount. The profiles and interconversion of soy
      germ isoflavones via Monascus aged vinegar soaking were investigated, and the
      distribution in vinegars were also explored. The aglycones were dramatically
      increased by 40.76 times. Concomitantly, beta-glycosides and malonylglycosides
      were significantly decreased. The proportion of aglycones presented a sharp
      increase with the endogenous beta-glucosidase activity at the initial 4h
      incubation. There appeared to be correlations between beta-glucosidase activity
      and the hydrolysis of conjugated isoflavones. The results demonstrated that the
      reactions of decarboxylation, de-esterification and de-glycosylation were
      involved in the Monascus aged vinegar soaking, supporting synergistic effects of
      enzymolysis by endogenous beta-glucosidase from soy germ and acid hydrolysis of
      vinegars. Soaking by vinegar is a promising pathway for preparing aglycone-rich
      soy germ. 

PMID- 25976820
TI  - Metabolic mechanism of phenyllactic acid naturally occurring in Chinese pickles.
AB  - Phenyllactic acid, a phenolic acid phytochemical with the antimicrobial activity,
      was rarely reported in food besides honey and sourdough. This study evidenced a
      new food source of phenyllactic acid and elucidated its metabolic mechanism.
      Phenyllactic acid naturally occurred in Chinese pickles with concentrations
      ranged from 0.02 to 0.30 mM in 23 pickle samples including homemade and
      commercial ones. Then, lactic acid bacteria capable of metabolizing phenyllactic
      acid were screened from each homemade pickle and a promising strain was
      characterized as Lactobacillus plantarum. Moreover, the investigation of the
      metabolic mechanism of phenyllactic acid in pickles suggested that the yield of
      phenyllactic acid was positively related to the content of phenylalanine in food,
      and the addition of phenylalanine as precursor substance could significantly
      promote the production of phenyllactic acid. This investigation could provide
      some insights into the accumulation of phenyllactic acid in pickle for long
      storage life.

PMID- 25976821
TI  - Phenolic trend and hygienic quality of green table olives fermented with
      Lactobacillus plantarum starter culture.
AB  - In this paper, four different olive cultivars from Southern Italy, Carolea,
      Cassanese, Nocellara del Belice, Nocellara Messinese table olives, produced
      according to traditional fermentation processes, were evaluated with the aim of
      assessing the effect of selected starter cultures on growth of bacterial
      population and on olive phenols during fermentation. Only Cassanese and Nocellara
      del Belice inoculated samples reached a safe pH value under 4.6 after 90 days
      while maintaining it until the end of storage. The most representative phenols in
      brine samples analysed by HPLC-MS/MS were hydroxytyrosol and verbascoside. Among
      the analysed phenols, only hydroxytyrosol, caffeic acid and ferulic acid always
      increased during fermentation, while the others increased up to 90-120 days and
      then decreased. The Principal Component Analysis (PCA) performed on pH and phenol
      values highlighted three clusters of olive cultivars. Throughout the brining
      period, lactic acid bacteria were always present while staphylococci and coliform
      bacteria disappeared after 30 and 90 days, respectively.

PMID- 25976822
TI  - The effects of juice processing on black mulberry antioxidants.
AB  - Black mulberry fruit is processed to juice at significant scale in Turkey. The
      effect of industrial-scale juice production on black mulberry antioxidants was
      evaluated using samples collected from the main steps of processing; including
      the selection of fruits, washing, mechanical milling, mashing, cold pressing,
      pasteurization, and filling-packing. Two major anthocyanins (cyanidin-3-glucoside
      and cyanidin-3-rutinoside), two phenolic acids (3- and caffeoylquinic acid) and 3
      flavonols (rutin, quercetin-3-glucoside, and quercetin-malonyl-glucoside) were
      identified using LC-QTOF-MS and were quantified using HPLC. Approximately, 60-70%
      of the fruit anthocyanins were retained in the final juice, which also contained
      high levels of caffeoylquinic acids, relative to the fruit. Mashing and pressing
      were the steps which were effective for the recovery of fruit polyphenolics into
      the juice fraction. Moreover, an in vitro gastrointestinal digestion model,
      applied to determine the effect of processing on the bioavailability of mulberry
      antioxidants, indicated a higher anthocyanin bioavailability for the fruit matrix
      than for the juice matrix. 

PMID- 25976823
TI  - Compositional and gastrointestinal prokinetic studies of Pugionium (L.).
AB  - Pugionium cornutum (L.) Gaertn. (PCG) is a desert plant with edible and medicinal
      value. The contents of proximate composition, amino acids and vitamins of fresh
      and pickled PCG were analyzed. PCG is rich in dietary fiber, protein and
      vitamins. PCG is a dietary source of potassium and calcium, with low levels of
      fat and sugar. PCG contains all the 18 hydrolyzed amino acids. Pickled PCG
      protein is a high quality protein. A large quantity of vitamins are lost during
      the pickling process. The type and number of mice dejections, gastric emptying
      and intestinal propulsion were investigated using the water extract of fresh and
      pickled PCG (WEFP and WEPP) to determine their gastrointestinal prokinetic
      efficacy. The low-dose WEFP and WEPP promoted the gastrointestinal dynamics and
      the WEFP and WEPP promoted gastrointestinal activity and act as nonviolent drugs.
      The results indicate that PCG has great potential as a new functional food
      source. 

PMID- 25976824
TI  - Interaction between Z-ligustilide from Radix Angelica sinensis and human serum
      albumin.
AB  - Z-ligustilide (LIG), an essential oil extract from Radix Angelica sinensis, has
      broad pharmaceutical applications in treating cardiovascular and cerebrovascular
      diseases. Interaction of LIG with the major transport protein of human blood
      circulation, human serum albumin (HSA) has been investigated by steady-state, UV
      vis and circular dichroism (CD) spectroscopic methods, as well as the effect of
      metal ions (e.g. Zn(2+), Cu(2+), Fe(3+), Co(2+), Ni(2+)) on the LIG-HSA system.
      Fluorescence results revealed that a moderate binding affinity (1.59 * 10(4) M(
      1) at 298 K) between LIG and HSA with a 1:1 stoichiometry. Thermodynamic analysis
      of the binding data (DeltaS = +12.96 J mol(-1) K(-1) and DeltaH =- 20.11 kJ mol(
      1)) suggested the involvement of hydrophobic and van der Waals forces, as well as
      hydrogen bonding in the complex formation. The specific binding distance r (3.75
      nm) between donor (Trp-214) and acceptor (LIG) was obtained according to
      fluorescence resonance energy transfer. CD results showed that slight
      conformational changes occurred in the protein upon complexation with LIG.

PMID- 25976825
TI  - Genetic and phytochemical variability of six Teucrium arduini L. populations and
      their antioxidant/prooxidant behaviour examined by biochemical, macromolecule-
      and cell-based approaches.
AB  - Teucrium arduini L., an Ilyric-Balcanic endemic species, has been reported for
      decades as a valuable plant used in traditional medicine for treating digestive
      disorders. The present study evaluated genetic and phytochemical variability of
      six T. arduini populations in order to determine factors that influence an
      accumulation of polyphenolic compounds. Results strongly suggest that a
      phytochemical variation was caused by environmental rather than genetic factors.
      T. arduini leaf extract from the locality Ucka, which accumulated significantly
      more polyphenolic phytochemicals in comparison to others, showed antioxidant
      activity in DNA and lipid bioassays. Furthermore, the same extract exhibited
      prooxidant behaviour at protein level and induce formation of reactive oxygen
      species in human laryngeal carcinoma cells causing cytotoxic activity, in a dose
      dependent manner. All the results of the present study suggested that T. arduini
      extract could be responsible for antioxidative/prooxidative mechanisms and would
      help in determination of optimal conditions for their ethnopharmacological use. 

PMID- 25976826
TI  - Molecular cloning and expression analysis of a Cu/Zn SOD gene (BcCSD1) from
      Brassica campestris ssp. chinensis.
AB  - Superoxide dismutases (SODs) are a family of metalloproteins extensively exists
      in eukaryote, which plays an essential role in stress-tolerance of higher plants.
      A full-length cDNA encoding Cu/Zn SOD (BcCSD1) was isolated from young seedlings
      of non-heading Chinese cabbage (Brassica campestris ssp. chinensis) by rapid
      amplification of cDNA ends (RACE). Bioinformatics analysis revealed that BcCSD1
      belonged to the plant SOD super family and had the closest relationship with SOD
      from Brassica napus. Tissue expression pattern analysis revealed that the BcCSD1
      was constitutively expressed in all the tested tissues, and strongest in leaf,
      moderate in stem, lowest in root. The expression profiles under different stress
      treatments such as drought, NaCl, high temperature and ABA were also
      investigated, and the results revealed that BcCSD1 was a stress-responsive gene,
      especially to ABA. These results provide useful information for further
      understanding the role of BcCSD1 resistant to abiotic stress in Brassica
      campestris in the future. 

PMID- 25976827
TI  - Ammonium reduces oxalate accumulation in different spinach (Spinacia oleracea L.)
      genotypes by inhibiting root uptake of nitrate.
AB  - Excessive accumulation of oxalate negatively affects nutritional value of many
      vegetables, such as spinach (Spinacia oleracea L.). Mixed solution of ammonium
      and nitrate could effectively reduce oxalate accumulation, while the mechanism
      involved remains unknown. High (Heizhenzhu) and low (Weilv) oxalate-accumulated
      spinach genotypes were used in this study to investigate the association of
      oxalate accumulation and root uptake of nitrogen. Exposure of increasing nitrate
      or mixed-nitrogen (nitrate:ammonium = 1:1) significantly increased leaf total and
      soluble oxalate contents. In contrast, increasing ammonium did not result in
      elevation of leaf oxalate. Correlation analysis confirmed that leaf oxalate
      accumulation was positively associated with root uptake of nitrate but not
      ammonium. Moreover, addition of ammonium significantly reduced nitrate uptake
      rate, and subsequently decreased leaf oxalate accumulation. The results suggest
      that oxalate synthesis in spinach leaves is associated with its root uptake of
      nitrate, and ammonium is able to reduce oxalate accumulation by inhibiting uptake
      of nitrate.

PMID- 25976828
TI  - Changes in total nitrogen and amino acid composition of New Zealand Undaria
      pinnatifida with growth, location and plant parts.
AB  - Undaria pinnatifida is known as unwanted organism in New Zealand. However, Wakame
      is a traditional food made of U. pinnatifida, which is now cultured extensively
      in East Asia. Therefore, it is important to examine this introduced alga as a
      potential source of dietary protein for human consumption in New Zealand. This
      study determined total nitrogen content and amino acid profile of New Zealand U.
      pinnatifida harvested from the Marlborough Sounds on a monthly basis from June to
      November 2011. Total average nitrogen content and crude protein content was 21.02
      mg/g dry weight and 13.1% of dry weight, respectively. The three most abundant
      amino acids that contributed to flavour (glutamic acid, aspartic acid and
      alanine) were present and the most abundant essential amino acids were arginine,
      leucine, lysine and valine. The results showed that the amino acid content in
      blades from the exposed farm was significantly higher (P < 0.05) than the others.
      Sporophyll maturation of U. pinnatifida in New Zealand influenced protein content
      and amino acid composition. Sporophyll, considered as a waste product by many,
      was found to be a potentially good source of protein.

PMID- 25976830
TI  - Time to change.

PMID- 25976829
TI  - Effect of teicoplanin on Staphylococcus aureus with heterointermediate
      susceptibility to glycopeptides in experimental infective endocarditis model.

PMID- 25976831
TI  - Deep venous thrombosis identification from analysis of ultrasound data.
AB  - PURPOSE: The purpose of this research was to determine whether combined
      ultrasound- and sensor-based compressibility and augmented blood flow measures
      yielded better results for DVT detection than for the individual measures alone.
      METHODS: Twenty-six limbs from 19 patients were scanned using a sensorized
      ultrasound DVT screening system, and compressibility and flow measures were
      obtained at 125 locations. Results from conventional compression ultrasound
      examination were used as gold standard, with seven vessels (four patients)
      positive for DVT. A classification approach was used to combine the individual
      DVT measures per vessel and generate an optimal feature for every possible
      combination of individual measures. Sensitivity and specificity were calculated
      for the individual measures and for all combined measures, as was a usefulness
      criteria [Formula: see text] for measuring class separability. RESULTS: Seven
      optimal combined features were found with 100% sensitivity and 100% specificity,
      with the best combined feature having a [Formula: see text] value over two orders
      of magnitude greater than the best individual DVT measure. CONCLUSIONS: The
      proposed approach for DVT detection combines different aspects of thrombus
      detection in a novel way generating a quantifiable measure and outperforms any of
      the individual measures when used independently. All of the combined measures
      included the flow measure as well as the slope compressibility measure, which
      uses the magnitude of the force applied by the ultrasound probe, suggesting that
      these measurements provide important information when characterizing DVT.

PMID- 25976832
TI  - Online tracking of interventional devices for endovascular aortic repair.
AB  - PURPOSE: The continuous integration of innovative imaging modalities into
      conventional vascular surgery rooms has led to an urgent need for computer
      assistance solutions that support the smooth integration of imaging within the
      surgical workflow. In particular, endovascular interventions performed under 2D
      fluoroscopic or angiographic imaging only, require reliable and fast navigation
      support for complex treatment procedures such as endovascular aortic repair.
      Despite the vast variety of image-based guide wire and catheter tracking methods,
      an adoption of these for detecting and tracking the stent graft delivery device
      is not possible due to its special geometry and intensity appearance. METHODS: In
      this paper, we present, for the first time, the automatic detection and tracking
      of the stent graft delivery device in 2D fluoroscopic sequences on the fly. The
      proposed approach is based on the robust principal component analysis and extends
      the conventional batch processing towards an online tracking system that is able
      to detect and track medical devices on the fly. RESULTS: The proposed method has
      been tested on interventional sequences of four different clinical cases. In the
      lack of publicly available ground truth data, we have further initiated a crowd
      sourcing strategy that has resulted in 200 annotations by unexperienced users,
      120 of which were used to establish a ground truth dataset for quantitatively
      evaluating our algorithm. In addition, we have performed a user study amongst our
      clinical partners for qualitative evaluation of the results. CONCLUSIONS:
      Although we calculated an average error in the range of nine pixels, the fact
      that our tracking method functions on the fly and is able to detect stent grafts
      in all unfolding stages without fine-tuning of parameters has convinced our
      clinical partners and they all agreed on the very high clinical relevance of our
      method.

PMID- 25976833
TI  - Interactive virtual stent planning for the treatment of coarctation of the aorta.
AB  - PURPOSE: The coarctation of the aorta (CoA), a local narrowing of the aortic
      arch, accounts for 7 % of all congenital heart defects. Stenting is a recommended
      therapy to reduce the pressure gradient. This procedure is associated with
      complications such as the development of adverse flow conditions. A computer
      aided treatment planning based on flow simulations can help to predict possible
      complications. The virtual stent planning is an important, intermediate step in
      the treatment planning pipeline. We present a novel approach that automatically
      suggests a stent setup and provides a set of intuitive parameters that allow for
      an interactive adaption of the suggested stent placement and induced deformation.
      METHODS: A high-quality mesh and a centerline are automatically generated. The
      stent-induced deformation is realized through a deformation of the centerline and
      a vertex displacement with respect to the deformed centerline and additional
      stent parameters. The parameterization is automatically derived from the
      underlying data and can be optionally altered through a condensed set of
      clinically sound parameters. RESULTS: The automatic deformation can be generated
      in about 25 s on a consumer system. The interactive adaption can be performed in
      real time. Compared with manual expert reconstructions of the stented vessel
      section, the mean difference of vessel path and diameter is below 1 mm.
      CONCLUSION: Our approach enables a medical user to easily generate a plausibly
      deformed vessel mesh which is necessary as input for a simulation-based treatment
      planning of CoA.

PMID- 25976834
TI  - Comment on "When to perform hepatic resection for intermediate-stage
      hepatocellular carcinoma".

PMID- 25976836
TI  - Identification of inhibitors of bacterial RNA polymerase.
AB  - Very few clinically available antibiotics target bacterial RNA polymerase (RNAP)
      suggesting it is an underutilized target. The advent of detailed structural
      information of RNAP holoenzyme (HE) has allowed the design and in silico
      screening of novel transcription inhibitors. Here, we describe our approach for
      the design and testing of small molecule transcription inhibitors that work by
      preventing the interaction between the essential transcription initiation factor
      sigma and RNAP. With the appropriate structural information this approach can be
      easily modified to other essential protein-protein interactions. 

PMID- 25976835
TI  - Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect.
AB  - Passively administered anti-tumor monoclonal antibodies (mAbs) rapidly kill tumor
      targets via FcgammaR-mediated cytotoxicity (ADCC), a short-term process. However,
      anti-tumor mAb treatment can also induce a vaccinal effect, in which mAb-mediated
      tumor death induces a long-term anti-tumor cellular immune response. To determine
      how such responses are generated, we utilized a murine model of an anti-tumor
      vaccinal effect against a model neoantigen. We demonstrate that FcgammaR
      expression by CD11c(+) antigen-presenting cells is required to generate anti
      tumor T cell responses upon ADCC-mediated tumor clearance. Using FcgammaR
      humanized mice, we demonstrate that anti-tumor human (h)IgG1 must engage
      hFcgammaRIIIA on macrophages to mediate ADCC, but also engage hFcgammaRIIA, the
      sole hFcgammaR expressed by human dendritic cells (DCs), to generate a potent
      vaccinal effect. Thus, while next-generation anti-tumor antibodies with enhanced
      binding to only hFcgammaRIIIA are now in clinical use, ideal anti-tumor
      antibodies must be optimized for both cytotoxic effects as well as hFcgammaRIIA
      engagement on DCs to stimulate long-term anti-tumor cellular immunity. 

PMID- 25976837
TI  - Systems biology approaches to defining transcription regulatory networks in
      halophilic archaea.
AB  - To survive complex and changing environmental conditions, microorganisms use gene
      regulatory networks (GRNs) composed of interacting regulatory transcription
      factors (TFs) to control the timing and magnitude of gene expression. Genome-wide
      datasets; such as transcriptomics and protein-DNA interactions; and experiments
      such as high throughput growth curves; facilitate the construction of GRNs and
      provide insight into TF interactions occurring under stress. Systems biology
      approaches integrate these datasets into models of GRN architecture as well as
      statistical and/or dynamical models to understand the function of networks
      occurring in cells. Previously, these types of studies have focused on
      traditional model organisms (e.g. Escherichia coli, yeast). However, recent
      advances in archaeal genetics and other tools have enabled a systems approach to
      understanding GRNs in these relatively less studied archaeal model organisms. In
      this report, we outline a systems biology workflow for generating and integrating
      data focusing on the TF regulator. We discuss experimental design, outline the
      process of data collection, and provide the tools required to produce high
      confidence regulons for the TFs of interest. We provide a case study as an
      example of this workflow, describing the construction of a GRN centered on multi
      TF coordinate control of gene expression governing the oxidative stress response
      in the hypersaline-adapted archaeon Halobacterium salinarum. 

PMID- 25976838
TI  - One-year evaluation of inactive occlusal enamel lesions in children and
      adolescents.
AB  - OBJECTIVES: The aims of this study were to compare caries incidence and
      progression on sound occlusal surfaces and on surfaces presenting inactive enamel
      lesions in children and adolescents over 1 year and to estimate the risk of
      caries incidence and progression on these surfaces. METHODS: This prospective
      cohort study followed 200 7-15-year-old caries-inactive schoolchildren over 1
      year. Stage of eruption, occlusal plaque, and occlusal caries were recorded on
      permanent molars. Statistical analysis was performed using generalized estimating
      equations with a logistic link function. RESULTS: Twenty-two children (11 %)
      presented "caries progression" (at least one active lesion on molar teeth). At
      site level, no difference was observed in caries incidence and progression
      between sites classified either sound (2.6 %) or with inactive enamel lesion (3.9
      %) at the baseline examination (chi (2) test, p = 0.48). Adjusted for plaque,
      stage of eruption, type of molar and dental arch, inactive enamel lesions
      presented a similar risk for caries progression than sound occlusal surfaces (OR
      = 0.98, 95 % CI = 0.40-2.38). CONCLUSION: Within the limitations of this study,
      no difference was observed in caries incidence, progression, and risk on sound
      occlusal sites in comparison with sites presenting inactive enamel lesions.
      CLINICAL RELEVANCE: Occlusal surfaces harboring inactive caries lesions did not
      require additional attention than the one normally given to sound occlusal
      surfaces over a 1-year period.

PMID- 25976839
TI  - Delirium: the lived experience of older people who are delirious post-orthopaedic
      surgery.
AB  - Delirium is a common, potentially preventable and reversible cause of
      postoperative functional disability, morbidity, and mortality. It can lead to
      increased health-care use and also poses a substantial challenge for nurses
      caring for patients who experience delirium after surgery. Predominantly, the
      published work concentrates on diagnosis, reduction of the modifiable risk
      factors, and treatments. Compared with this body of published work, the
      experience of delirium from a patient's perspective has been largely ignored
      except for a limited number of qualitative research reports. The importance of
      researching the lived experience of delirium is that a better understanding may
      lead to more empathic, therapeutic nursing care and help other sufferers to know
      they are not alone. The aims of the study were to explore and clarify the lived
      experience of delirium. Eleven patients were recruited to the study following
      discharge post-surgery from an orthopaedic ward of a major tertiary hospital. The
      study used a qualitative descriptive approach and incorporated grounded theory
      data analysis processes. The findings of this study provide an insight into the
      incomprehensible emotional pain suffered by patients while they were delirious
      and the disparate feelings of remorse, guilt, and shame they experienced after
      the episode of delirium. Following this study, recommendations for nursing
      practice include formal follow-up support for patients with post-delirium
      episodes and more research into the long-term impact of the experience of
      delirium. 

PMID- 25976840
TI  - Assessment of acute stroke cerebral CT examinations by anaesthesiologists.
AB  - BACKGROUND AND PURPOSE: It is essential to diagnose ischaemic stroke as soon as
      possible after symptom onset, so that thrombolytic treatment can be initiated as
      quickly as possible. This might be greatly facilitated if cerebral CT could be
      carried out in a pre-hospital setting. The aim of this study was to evaluate if
      anaesthesiologists, who in Norway provide pre-hospital medical care, could be
      trained to assess cerebral CT scans to exclude radiological contraindications for
      thrombolytic stroke treatment. METHODS: Thirteen anaesthesiologists attended an 8
      h course in acute stroke assessment, including a 2-h introduction to the
      neuroradiology of acute stroke. Each participant then assessed 12 non-contrast
      cerebral CT examinations of acute stroke patients with specific regard to
      radiological contraindications for thrombolytic therapy. Test results were
      compared with those of three experienced neuroradiologists. Inter-rater agreement
      between anaesthesiologists and neuroradiologists was calculated using Cohen's
      Kappa statistics. Robustness of the results was assessed using the non-parametric
      bootstrap. RESULTS: Among the neuroradiologists, Kappa was 1 for detecting
      radiological contraindications for thrombolytic therapy. Twelve of the 13
      anaesthesiologists showed good or excellent agreement (Kappa > 0.60) with the
      neuroradiologists. The anaesthesiologists spent a median time of 2 min and 18 s
      on each CT scan. CONCLUSIONS: This study suggests that anaesthesiologists who are
      experienced in pre-hospital care may be quickly trained to assess cerebral CT
      examinations in acute stroke patients with regard to radiological
      contraindications for thrombolytic therapy.

PMID- 25976841
TI  - Abscisic acid affects transcription of chloroplast genes via protein phosphatase
      2C-dependent activation of nuclear genes: repression by guanosine-3'-5'
      bisdiphosphate and activation by sigma factor 5.
AB  - Abscisic acid (ABA) represses the transcriptional activity of chloroplast genes
      (determined by run-on assays), with the exception of psbD and a few other genes
      in wild-type Arabidopsis seedlings and mature rosette leaves. Abscisic acid does
      not influence chloroplast transcription in the mutant lines abi1-1 and abi2-1
      with constitutive protein phosphatase 2C (PP2C) activity, suggesting that ABA
      affects chloroplast gene activity by binding to the pyrabactin resistance
      (PYR)/PYR1-like or regulatory component of ABA receptor protein family
      (PYR/PYL/RCAR) and signaling via PP2Cs and sucrose non-fermenting protein-related
      kinases 2 (SnRK2s). Further we show by quantitative PCR that ABA enhances the
      transcript levels of RSH2, RSH3, PTF1 and SIG5. RelA/SpoT homolog 2 (RSH2) and
      RSH3 are known to synthesize guanosine-3'-5'-bisdiphosphate (ppGpp), an inhibitor
      of the plastid-gene-encoded chloroplast RNA polymerase. We propose, therefore,
      that ABA leads to an inhibition of chloroplast gene expression via stimulation of
      ppGpp synthesis. On the other hand, sigma factor 5 (SIG5) and plastid
      transcription factor 1 (PTF1) are known to be necessary for the transcription of
      psbD from a specific light- and stress-induced promoter (the blue light
      responsive promoter, BLRP). We demonstrate that ABA activates the psbD gene by
      stimulation of transcription initiation at BLRP. Taken together, our data suggest
      that ABA affects the transcription of chloroplast genes by a PP2C-dependent
      activation of nuclear genes encoding proteins involved in chloroplast
      transcription. 

PMID- 25976843
TI  - Is carpal tunnel release associated with trigger finger?

PMID- 25976842
TI  - Effectiveness of flexor tenolysis in zone II: A retrospective series of 40
      patients at 3 months postoperatively.
AB  - Flexor tendon tenolysis consists of the surgical release of adhesions formed
      around tendons that persist despite splinting and appropriate rehabilitation. The
      aim of this study was to evaluate the increase in active range of motion
      following flexor tenolysis in zone II and to document the ensuing complications.
      Sixty patients (75 fingers) underwent zone II flexor tenolysis following flexor
      tendon injury, with or without dorsal tenolysis or PIP arthrolysis. Tenolysis
      cases following tendon graft or replantation were excluded. Both passive and
      active ranges of motion were measured at metacarpophalangeal, proximal and distal
      interphalangeal joints preoperatively and postoperatively at 6 weeks (57
      patients) and 3 months (40 patients). These measurements were completed by a
      functional evaluation using the Strickland classification. Any complications were
      noted. Mean preoperative total active motion (TAM) was 128 degrees , increasing
      postoperatively to 188 degrees  at 6 weeks and 192 degrees  at 3 months. Mean
      increase in TAM for patients undergoing tenolysis only was 60 degrees , compared
      to 90 degrees  in those undergoing tenolysis with arthrolysis. The functional
      outcome at 6 weeks was excellent in 23% of cases, good in 47%, average in 20% and
      poor in 10%. Deep flexor tendon rupture occurred in seven cases. Palmar flexor
      tenolysis can improve active range of motion of the fingers, and consequently,
      function. 

PMID- 25976844
TI  - Application of ultrasound-guided core biopsy as a novel diagnostic tool for base
      of tongue cancer: Our experiences with ten patients.

PMID- 25976846
TI  - Policy to improve England's diet has failed, study finds.

PMID- 25976845
TI  - Evaluation of the efficacy of meloxicam for post-operative management of pain and
      inflammation in horses after orthopaedic surgery in a placebo controlled clinical
      field trial.
AB  - BACKGROUND: The benefit of pre and post-operative administration of non-steroidal
      anti-inflammatory drugs for the relief of post-operative pain and control of
      inflammation in horses following orthopaedic surgery has not been previously
      investigated in controlled clinical field trials, and the utility of such
      treatment is a matter of ongoing dispute. Recently the utility of post-operative
      pain management was emphasized. It was therefore our aim to determine the
      efficacy of meloxicam in horses following partial resection of fractured splint
      bones. This condition was selected since the limited extent of the insult and the
      defined surgical intervention allowed the conduct of a randomized, double
      blinded, placebo-controlled, parallel group, multi-centre clinical field study in
      a homogenous patient population. RESULTS: Sixty-six client owned horses requiring
      unilateral partial splint bone resection were recruited in 15 centres in Germany
      and were allocated in a 1:1 ratio to receive meloxicam, 0.6 mg/kg for 5 days.
      Lameness at trot grades prior to surgery were similar in the meloxicam and
      placebo treatment groups but were significantly lower in the meloxicam group on
      day 6 post surgery. Clinical scores for soft tissue swelling and assessment of
      analgesic and anti-inflammatory efficacy by the investigators at the end of the
      study were significantly better for the meloxicam compared to the placebo group.
      No treatment-related adverse reactions were observed. CONCLUSION: The
      administration of meloxicam i.v. once prior to surgery followed by once daily
      oral administration for four consecutive days is efficacious for the control of
      post-operative pain and inflammation in horses undergoing orthopaedic surgery.

PMID- 25976847
TI  - Increased SUMO-1 expression in response to hypoxia: Interaction with HIF-1alpha
      in hypoxic pulmonary hypertension.
AB  - Pulmonary hypertension (PH) develops in 30-70% of chronic obstructive pulmonary
      disease patients and increases morbidity and mortality. The present study aimed
      to investigate the regulation of small ubiquitin-related modifier-1 (SUMO-1)
      expression in response to hypoxia. The experiments were carried out in vitro in
      rat pulmonary arterial smooth muscle cells (PASMCs) and in vivo using a rat
      hypoxic PH (HPH) model. A significant increase in SUMO-1 mRNA and protein levels
      was observed following hypoxic stimulation in vivo and in vitro. SUMO-1 is known
      to interact with various transcription factors, including hypoxia-inducible
      factor-1alpha (HIF-1alpha) in vitro. Notably, the expression of HIF-1alpha and
      its target gene, vascular endothelial growth factor, was increased by hypoxia in
      HPH. In addition, the present data suggest that SUMO-1 regulated HIF-1alpha in
      response to hypoxia (gene silencing and overexpression). Finally, the co
      immunoprecipitation assays suggest a direct and specific interaction between SUMO
      1 and HIF-1alpha. In conclusion, SUMO-1 may participate in the modulation of HIF
      1alpha through sumoylation in HPH. However, further studies are required to
      confirm this.

PMID- 25976848
TI  - Critical Assessment of the Foundations of Power Transmission and Distribution
      Reliability Metrics and Standards.
AB  - The U.S. federal government regulates the reliability of bulk power systems,
      while the reliability of power distribution systems is regulated at a state
      level. In this article, we review the history of regulating electric service
      reliability and study the existing reliability metrics, indices, and standards
      for power transmission and distribution networks. We assess the foundations of
      the reliability standards and metrics, discuss how they are applied to outages
      caused by large exogenous disturbances such as natural disasters, and investigate
      whether the standards adequately internalize the impacts of these events. Our
      reflections shed light on how existing standards conceptualize reliability,
      question the basis for treating large-scale hazard-induced outages differently
      from normal daily outages, and discuss whether this conceptualization maps well
      onto customer expectations. We show that the risk indices for transmission
      systems used in regulating power system reliability do not adequately capture the
      risks that transmission systems are prone to, particularly when it comes to low
      probability high-impact events. We also point out several shortcomings associated
      with the way in which regulators require utilities to calculate and report
      distribution system reliability indices. We offer several recommendations for
      improving the conceptualization of reliability metrics and standards. We conclude
      that while the approaches taken in reliability standards have made considerable
      advances in enhancing the reliability of power systems and may be logical from a
      utility perspective during normal operation, existing standards do not provide a
      sufficient incentive structure for the utilities to adequately ensure high levels
      of reliability for end-users, particularly during large-scale events. 

PMID- 25976849
TI  - A new method to measure intestinal secretion using fluorescein isothiocyanate
      inulin in small bowel of rats.
AB  - BACKGROUND: Small intestine ischemia can be seen in various conditions such as
      intestinal transplantation. To further understand the pathologic disruption in
      ischemia-reperfusion injury, we have developed a method to measure fluid changes
      in the intestinal lumen of rats. METHODS: Two 10-cm rat intestine segments were
      procured, connected to the terminal apertures of a perfusion device, and
      continuously infused with 3 mL of HEPES solution (control solution) containing 50
      MUM of fluorescein isothiocyanate (FITC)-inulin. The perfusion device consists of
      concentric chambers that contain the perfused bowel segments, which are
      maintained at 37 degrees C via H2O bath. The individual chamber has four
      apertures as follows: two fill and/or drain the surrounding HEPES solution on the
      blood side of the tissue. The others provide flow of HEPES solution containing
      FITC-inulin through the lumens. The experimental intestine was infused with the
      same solution with 100 MUM of Forskolin. A pump continuously circulated solutions
      at 6 mL/min. Samples were collected at 15-min intervals until 150 min and were
      measured by the nanoflourospectrometer. RESULTS: A mean of 6-MUM decrease in the
      FITC-inulin concentration in the Forskolin-treated experimental intestine was
      observed in comparison with that in the control intestine. The FITC-inulin count
      dilution in the experimental intestine is a result of an increase of fluid
      secretion produced by the effect of Forskolin, with P values <0.0001.
      CONCLUSIONS: We demonstrate that it is possible to measure luminal fluid changes
      over time using our new modified perfusion system along with FITC-inulin to allow
      real-time determinations of fluid and/or electrolyte movement along the small
      intestine.

PMID- 25976850
TI  - Protective effects of butyrate on intestinal ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Butyrate is normally fermented from undigested fiber by intestinal
      microflora. The goal of the present study was to determine the effects of
      butyrate and its underlying mechanisms on intestinal injury in a rat model of
      ischemia and reperfusion (I/R). METHODS: Male Sprague-Dawley rats were subjected
      to warm ischemia for 45 min by clamping the superior mesenteric artery after
      treatment with butyrate, followed by 6 and 72 h of reperfusion. Pathologic
      histology analysis, enzyme-linked immunosorbent assay, immunofluorescence, and
      Western blot were performed. RESULTS: Butyrate preconditioning markedly improved
      intestinal injury. The inflammatory factor levels and leukocyte infiltration were
      attenuated by butyrate. Butyrate also maintained the intestinal barrier
      structures, increased the expression of tight junction proteins, and decreased
      endotoxin translocation. CONCLUSIONS: We conclude that butyrate administration
      attenuates intestinal I/R injury, which is associated with preservation of
      intestinal tight junction barrier function and suppression of inflammatory cell
      infiltration in the intestinal mucosa. This suggests butyrate as a potential
      strategy to prevent intestinal I/R injury.

PMID- 25976851
TI  - Substernal goiter: when is a sternotomy required?
AB  - BACKGROUND: Sternotomy for substernal goiters (SSG) is associated with greater
      morbidity than a cervical approach to thyroidectomy. We sought to identify
      predictors for sternotomy as a surgical approach for the removal of SSG and
      analyzed the preoperative and postoperative characteristics of patients with SSG
      compared with those with large goiters contained entirely within the neck or a
      cervical goiter. METHODS: A retrospective review of a surgical database was
      performed. We included patients with large (>100 g) thyroids or SSG, regardless
      of size. Between 1995 and 2013, 220 patients met these criteria. Comparisons were
      made between patients who had an SSG and patients who had a cervical goiter with
      particular focus on those who required sternotomy. RESULTS: Of the 220 patients,
      127 patients (58%) had SSG, of whom 7 (5.5%) required sternotomy. All patients
      who underwent sternotomy underwent preoperative computed tomography scanning and
      were more likely to have preoperative symptoms of chest pressure and voice
      complaints and have extension of the thyroid gland below the aortic arch.
      Sternotomy took an average of 2 hours longer than a cervical incision, was
      associated with significantly more blood loss (600 versus 190 mL, P = 0.04), and
      a longer length of stay (3.1 versus 1.8 d, P = 0.03) than cervical thyroidectomy.
      CONCLUSIONS: Sternotomy for SSG is rare. All patients necessitating sternotomy
      had extension below the aortic arch and were more likely to present complaining
      of chest pressure and voice issues.

PMID- 25976852
TI  - Postmastectomy radiation therapy in T3 node-negative breast cancer.
AB  - BACKGROUND: In the absence of lymph node involvement, tumor size is arguably the
      most important prognostic factor for women with breast cancer. Radiation therapy
      use in the T3 node-negative population is controversial. We investigated the use
      of postmastectomy radiation therapy (PMRT) in women with T3 node-negative breast
      cancer. METHODS: A retrospective cohort study was conducted by identifying women
      with T3 node-negative breast cancer from the 1988-2009 Surveillance, Epidemiology
      and End Results database. Our primary outcome was breast cancer-specific
      survival. Survival curves were generated using the Kaplan-Meier method. Cox
      proportional hazard ratios (HRs) and propensity score analysis were used to
      evaluate the impact on survival. RESULTS: We identified 2874 patients with T3
      node-negative breast cancer and 961 (33%) received PMRT and 1913 (67%) did not.
      Statistically significant differences were seen in adjuvant radiation therapy use
      based on patient age, marital status, tumor grade, tumor size, and receptor
      status (P < 0.05 for all). Overall survival was lower in the PMRT group in
      unadjusted analysis (crude HR, 0.718; 95% confidence interval [CI], 0.614-0.840);
      however, adjusted HRs demonstrated no difference in overall survival (adjusted
      HR, 0.898; 95% CI, 0.765-1.054). Unadjusted analysis of breast cancer-specific
      survival demonstrated no difference between those who received PMRT and those who
      did not (crude HR, 0.834; 95% CI, 0.682-1.021). Propensity score analysis
      demonstrated no difference in breast cancer-specific survival based on PMRT use
      (adjusted HR, 0.939; 95% CI, 0.762-1.157). CONCLUSIONS: Analysis of the
      Surveillance, Epidemiology and End Results database suggests that receipt of PMRT
      is not clinically beneficial in T3 node-negative breast cancer.

PMID- 25976853
TI  - Late mortality in females after endovascular aneurysm repair.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) rupture is an adverse arterial
      remodeling event with high mortality risk. Because females have increased rupture
      risk with smaller AAAs (<5.5 cm), many recommend elective repair before the AAA
      reaches 5.5 cm. Elective repair improves survival for large AAAs, but long-term
      benefits of endovascular aneurysm repair (EVAR) for small AAAs in females remain
      less understood. The objective of this study was to identify if differences in
      late mortality exist between females undergoing elective EVAR at our institution
      for small and/or slow-growing AAAs compared with those who meet standard
      criteria. METHODS: We retrospectively analyzed all patients that underwent EVAR
      for infrarenal AAA from June, 2009-June, 2013. We excluded patients that were
      male, treated emergently or for iliac artery aneurysm, and that received renal
      and/or mesenteric artery stenting. Patients did not meet anatomic criteria if
      preoperative AAA diameter was <5.5 cm or enlarged <0.5 cm over 6 mo. Late
      mortality was assessed from the social security death index. RESULTS: Thirty-six
      of 162 elective EVAR patients (22.2%) were female (mean follow-up, 37.2 mo).
      Twenty patients (55.6%) met AAA size and/or growth criteria, whereas 16 (44.4%)
      did not meet criteria. Despite comparable demographics, comorbidities, and
      complications, patients that did not meet criteria had higher late mortality
      (37.5% versus 5%; P = 0.03) with a trend toward increased reoperation rate (25%
      versus. 5%; P = 0.48). Meeting size and/or growth criteria decreased odds of late
      death (odds ratio, 0.09; 95% confidence intervals, 0.01-0.83). CONCLUSIONS: There
      is increased late mortality in females receiving elective EVAR at our institution
      for small and/or slow-growing AAAs. This late mortality may limit the benefits of
      EVAR for this population.

PMID- 25976854
TI  - Optimal timing of tracheostomy after trauma without associated head injury.
AB  - BACKGROUND: Controversy exists over optimal timing of tracheostomy in patients
      with respiratory failure after blunt trauma. The study aimed to determine whether
      the timing of tracheostomy affects mortality in this population. METHODS: The
      2008-2011 National Trauma Data Bank was queried to identify blunt trauma patients
      without concomitant head injury who required tracheostomy for respiratory failure
      between hospital days 4 and 21. Restricted cubic spline analysis was performed to
      evaluate the relationship between tracheostomy timing and the odds of inhospital
      mortality. The cohort was stratified based on this analysis. Unadjusted
      characteristics and outcomes were compared. Multivariable logistic regression was
      used to evaluate the effect of tracheostomy timing on mortality after adjustment
      for age, gender, race, payor status, level of trauma center, injury severity
      score, presentation Glasgow coma scale, and thoracic and abdominal abbreviated
      injury score. RESULTS: There were 9662 patients included in the study. Restricted
      cubic spline analysis demonstrated a nonlinear relationship between timing of
      tracheostomy and mortality, with higher odds of mortality occurring with
      tracheostomy placement within 10 d of admission compared with later time points.
      The cohort was therefore stratified into early and delayed tracheostomy groups
      relative to this time point. The resulting groups contained 5402 (55.9%) and 4260
      (44.1%) patients, respectively. After multivariable adjustment, the delayed
      tracheostomy group continued to have significantly reduced odds of mortality
      (Adjusted odds ratio, 0.82, 95% confidence interval, 0.71-0.95, C-statistic,
      0.700). CONCLUSIONS: Among non-head injured blunt trauma patients with prolonged
      respiratory failure, tracheostomy placement within 10 d of admission may result
      in increased mortality compared with later time points.

PMID- 25976855
TI  - Intraperitoneal application of phospholipids for the prevention of postoperative
      adhesions: a possible role of myofibroblasts.
AB  - BACKGROUND: Peritoneal adhesions, organized as fibrous bands after abdominal
      surgery, are related with considerable morbidity and repeated hospitalization.
      Phospholipids, natural constituents of the peritoneal fluid, seem to display
      excellent antiadhesive properties. The aim of this study was to investigate
      whether intraperitoneal application of phospholipids is capable of reducing
      postoperative adhesions and the possible underlying mechanisms. MATERIALS AND
      METHODS: Twenty male Wistar rats were subjected to a midline laparotomy and a
      standard peritoneal and cecum abrasion trauma. Before laparotomy closure, a bolus
      of 3 mL of phospholipids (12 mg/mL) or NaCl (placebo) was given
      intraperitoneally. Seven days later, the quality and the quantity of adhesions,
      as well as serum proinflammatory and/or profibrotic mediators, were blindly
      assessed. Human colonic subepithelial myofibroblasts were isolated from normal
      controls and cultured with transforming growth factor-beta1 (TGFbeta1, 5 ng/mL)
      in the presence of phospholipids (30-300 MUg/mL). Collagen production in culture
      supernatants and migratory activity of myofibroblasts were also assessed.
      RESULTS: Phospholipids reduced intra-abdominal adhesions (P < 0.001), with
      respect to their intensity and area, and serum levels of cytokines (interleukin
      1beta, interleukin 6, platelet-derived growth factor-1, and TGFbeta1) compared
      with placebo-treated rats. Stimulation of myofibroblasts with TGFbeta1
      significantly increased (P < 0.001) the basic collagen production. The presence
      of phospholipids significantly reduced (P < 0.001) both the TGFbeta1 induced and
      the basic collagen production. Using a wound healing assay, phospholipids were
      found to reduce the basic and the TGFbeta1-induced migration of myofibroblasts in
      a concentration-dependent manner. CONCLUSIONS: Intraperitoneal phospholipids
      might be involved in the prevention of postoperative adhesions formation via the
      reduction of proinflammatory and/or profibrotic mediators and by inhibiting
      fibrogenic properties of mesenchymal cells.

PMID- 25976856
TI  - The diagnostic dilemma of identifying perforated appendicitis.
AB  - BACKGROUND: Despite extensive research, the classification of perforated (PA)
      versus nonperforated appendicitis (NPA) remains poorly defined. We hypothesize
      that the variability across specialties in the classification of appendicitis as
      PA or NPA may be associated with variation in clinical behavior as demonstrated
      by a variation in length of stay (LOS). METHODS: Retrospective review of 1311
      appendectomies over a 16-mo period from an independent children's hospital
      allowed a comparison of the diagnostic classification of appendicitis as PA or
      NPA based on radiology (R), operative (O), and pathology (P) reports. Three
      groups, P + O (n = 1241), P + R (n = 516), O + R (n = 512) were compared to
      identify interspecialty discordance in classification. The LOS was analyzed as a
      proxy for clinical behavior to test if the diagnostic classification was
      consistent with expected clinical behavior (NPA with LOS <=48 h and PA with LOS
      >48 h). RESULTS: The subsets P + O, P + R, and O + R revealed a discordance of
      11%, 15.7%, and 16.6% within the classification of appendicitis, respectively.
      Cases designated as PA in all subsets clinically behaved as PA with a mean LOS
      >48 h (97, 95, and 95 h, respectively), whereas the cases designated as NPA
      exhibited greater variation from the expected LOS <=48 h, with means 35, 83, and
      62 h, respectively. CONCLUSIONS: Variability in the classification of
      appendicitis between specialties suggests an error rate inherent in diagnosis.
      Standardizing the criteria for classification across specialties may improve the
      diagnostic accuracy of the type of appendicitis needed to identify best practices
      for optimal use of hospital resources and for meaningful clinical trials.

PMID- 25976857
TI  - Management of traumatic duodenal hematomas in children.
AB  - BACKGROUND: Duodenal hematomas from blunt abdominal trauma are uncommon in
      children and treatment strategies vary. We reviewed our experience with this
      injury at a large-volume children's hospital. MATERIALS AND METHODS: A
      retrospective case series was assembled from January 2003-July 2014. Data
      collected included demographics, clinical and radiographic characteristics, and
      hospital course. Patients with grade I injuries based on the American Association
      for the Surgery of Trauma Duodenum Injury Scale were compared with those with
      grade II injuries. RESULTS: Nineteen patients met inclusion criteria at a median
      age of 8.91 y (range, 1.7-17.2 y). Mechanisms of injury included direct abdominal
      blow or handle bar injury (n = 9), nonaccidental trauma (n = 5), falls (n = 3),
      and motor vehicle accident (n = 2). Ten patients had grade I hematomas and nine
      had grade II. Hematomas were most frequently seen in the second portion of the
      duodenum (n = 9). Five patients underwent a laparotomy for concerns for hollow
      viscus injury. No patients required operative drainage of the hematoma; however,
      one patient underwent percutaneous drainage. Twelve patients received parenteral
      nutrition (PN) for a median duration of 9 d (range, 5-14 d). Median duration of
      PN for grade I was 6.5 d (range, 5-8 d) versus 12 d for grade II (range, 9-14 d;
      P = 0.016). Complications included one readmission for concern of bowel
      obstruction requiring bowel rest. CONCLUSIONS: This study suggests that duodenal
      hematomas can be successfully managed nonoperatively. Grade II hematomas are
      associated with longer duration of PN therapy and consequently longer hospital
      stays. These data can assist in care management planning and parental counseling
      for patients with traumatic duodenal hematomas.

PMID- 25976858
TI  - The Changing Landscape of Surgical Education: What are Residency Education Teams
      and do we Need Them?
AB  - OBJECTIVES: This study aims to understand how general surgery training programs
      constitute their residency education team (RET), how they define the roles of RET
      members, and how they measure success of the team. It fundamentally asks the
      question, "What is a RET and do we need one?" DESIGN AND PARTICIPANTS: Program
      directors, associate program directors, educators, program coordinators, and
      chief residents from Accreditation Council for Graduate Medical Education (ACGME)
      general surgery training programs were asked to anonymously complete a survey
      categorized into 3 sections: (1) roles and responsibilities, (2) views of his/her
      RET and team members, and (3) general views about RETs. All respondents provided
      their opinions on the importance of a RET for administering and leading a
      surgical residency, whom the ideal members would be, and the main outcomes of a
      high-functioning RET. RESULTS: Respondents (n = 167) included 59 (35.3%) program
      directors, 16 (9.6%) associate program directors, 8 (4.8%) educators, 67 (40.1%)
      program coordinators, and 6 (3.6%) chief residents. Overall, 84.4% of respondents
      were a part of a RET, defined as 2 or more individuals who are responsible and
      accountable for oversight and conduct of the residency training program. RET
      respondents expressed statistically significantly and higher importance for a RET
      (p < 0.0001) than their non-RET counterparts. CONCLUSIONS: This study provides a
      snapshot of how some associated with general surgery residencies view and value
      RETs. The results of this survey are preliminary and suggest a need for educators
      within surgery programs and ambiguity about the role of associate program
      director. It also suggests that a closer look at role responsibilities may be of
      value, especially in view of the changing landscape of surgical education.
      Overall, most respondents felt that a RET was important to the main outcomes of a
      successful residency program.

PMID- 25976859
TI  - Characterization of intrinsic variability in time-series metabolomic data of
      cultured mammalian cells.
AB  - In an attempt to rigorously characterize the intrinsic variability associated
      with Chinese Hamster Ovary (CHO) cell metabolomics studies, supernatant and
      intracellular samples taken at 5 time points from duplicate lab-scale bioreactors
      were analyzed using a combination of gas chromatography (GC)- and liquid
      chromatography-mass spectrometry (LC-MS) based metabolomics. The intrinsic
      variability between them was quantified using the relative standard deviation
      (RSD), and the median RSD was 9.4% and 12.4% for supernatant and intracellular
      samples, respectively. When exploring metabolic changes between lab- and pilot
      scale bioreactors, a high number of metabolites (65-105) were significantly
      different when no corrections were made for this intrinsic variability. This
      distinction also extended to principal component and metabolic pathway analysis.
      However, when intrinsic variability was taken into account, the number of
      metabolite with significant changes reduced substantially (20-25) as did the
      separation in principal component and metabolic pathway analysis, suggesting a
      much smaller change in physiology across bioreactor scale. Our results also
      suggested the contribution of biological variability to the total variability
      across replicates (~0.4%) was significantly lower than that from technical
      variability (~9-12%). Our study highlights the need for understanding and
      accounting for intrinsic variability in CHO cell metabolomics studies. Failure to
      do so can result in incorrect biological interpretation of the observations which
      could ultimately lead to the identification of a suboptimal set of targets for
      genetic engineering or process development considerations.

PMID- 25976860
TI  - Primary family caregivers' observations and perceptions of their older relatives'
      knee osteoarthritis pain and pain management: a qualitative study.
AB  - AIM: To explore primary family caregivers' observations and perceptions of their
      older relatives' knee osteoarthritis pain and pain management. BACKGROUND:
      Osteoarthritis is one of the most common joint disorders in older people. Studies
      have mainly focused on spouses' or partners' perceptions of older individuals'
      osteoarthritis pain. DESIGN: Qualitative description. METHODS: Primary family
      caregivers of older outpatients with osteoarthritis (N = 28) were recruited by
      convenience from one medical centre in northern Taiwan and two regional hospitals
      in northern and eastern Taiwan in 2012. Data were collected in individual
      interviews using a semi-structured guide and analysed by content analysis.
      RESULTS: Primary family caregivers observed that their older relatives commonly
      mentioned that osteoarthritis pain interfered with their walking ability, daily
      activities, moods, sleep and social activities. Older adults commonly shared
      their pain with their family members. Participants observed that their older
      relatives with osteoarthritis used limited pain-management strategies to relieve
      pain, but participants provided few pain-management strategies to help their
      relatives. Most participants had limited knowledge about osteoarthritis pain.
      Some participants and their older relatives held negative attitudes towards using
      pain medicines. Most participants suggested that other families should bring
      their older relatives with osteoarthritis pain to see a doctor as soon as
      possible. CONCLUSION: Our results show that family caregivers were the main
      support for older people with osteoarthritis. Interventions should educate
      patients and family members about osteoarthritis causes, common misconceptions
      about osteoarthritis, osteoarthritis pain medicines and treatment and encourage
      family members' support.

PMID- 25976861
TI  - Identification of microRNAs in Nipple Discharge as Potential Diagnostic
      Biomarkers for Breast Cancer.
AB  - BACKGROUND: Intraductal breast cancer is generally difficult to diagnose because
      of a lack of an efficient method for detection. The purpose of this study was to
      reveal and validate the differential expression of microRNAs (miRNAs) in nipple
      discharge from intraductal papilloma patients and identify miRNAs as novel
      potential biomarkers for primary breast cancer. METHODS: Nipple discharge samples
      were collected from three intraductal carcinoma breast cancer patients and three
      intraductal papilloma patients. The initial screening of miRNA expression was
      performed with an Axon GenePix 4000B microarray scanner using a novel approach to
      label miRNAs. The expression levels of the miRNAs selected from the initial
      screening were further examined by quantitative real-time polymerase chain
      reaction (qRT-PCR) in 21 validation samples (8 carcinomas and 13 benign tumors).
      An independent t test was used to detect significant correlations between the
      miRNA expression levels and breast cancer. RESULTS: Microarray profiling
      demonstrated that three miRNAs were markedly up-regulated and three miRNAs were
      down-regulated in the intraductal carcinoma breast cancer patients compared to
      the papilloma group. The qRT-PCR analysis further verified that four miRNAs (miR
      4484, miR-K12-5-5p, miR-3646, and miR-4732-5p) might serve as potential tumor
      biomarkers for breast cancer detection. CONCLUSION: The novel approach of using a
      microarray scanner is applicable for studying biomarkers in nipple discharge
      containing small amounts of miRNA. miRNAs could serve as potential tumor
      biomarkers that can assist in breast cancer screening. Up-regulation of miR-4484,
      miR-K12-5-5p, and miR-3646 in nipple discharge may be a predictor of malignant
      breast cancer.

PMID- 25976862
TI  - Adjuvant Chemotherapy and Radiation Therapy is Associated with Improved Survival
      for Patients with Extrahepatic Cholangiocarcinoma.
AB  - BACKGROUND: This study aimed to analyze adjuvant therapy among patients with
      extrahepatic cholangiocarcinoma (EHC) at a national level. METHODS: The American
      College of Surgeons National Cancer Data Base was used to identify patients with
      resected EHC (pathologic stages 1-3) between 1998 and 2006 (n = 8741). Three
      groups were compared: surgery only (S, n = 5766), surgery plus adjuvant
      chemotherapy (AC, n = 450), and surgery plus adjuvant chemotherapy and radiation
      therapy (ACR, n = 1918). The study investigated how patient demographics,
      provider characteristics, and tumor-specific variables were associated with
      receipt of adjuvant therapy and overall survival. RESULTS: Patients who received
      adjuvant treatment were more likely to be younger (median age S, 70 years; AC, 65
      years; ACR, 63 years), in the highest income quartile (>$46,000: S, 38.3 %; AC,
      43.4 %; ACR, 44.7 %), and treated at a community cancer center (S, 43.0 %; AC,
      50.7 %; ACR, 52.9 %) (all p < 0.001). These patients also were more likely to
      have positive lymph nodes (S, 34.7 %; AC, 69.6 %; ACR, 63.3 %), positive surgical
      margins (S, 5.9 %; AC, 7.1 %; ACR, 10.7 %), and stage 3 disease (S, 21.4 %; AC,
      37.8 %; ACR, 37.9 %) (all p < 0.001). Multivariate analysis of the entire cohort
      showed improved survival with ACR (hazard ratio [HR] 0.82; 95 % confidence
      interval [CI] 0.75-0.91). The survival benefit was independent of margin status
      (R0: HR 0.88; 95 % CI 0.79-0.97; R1: HR 0.49; 95 % CI 0.38-0.62). CONCLUSIONS:
      This national analysis suggests that ACR are associated with improved survival
      for high-risk EHC patients, such as those with positive lymph nodes. Until
      randomized clinical trials are conducted, these may be the best available data to
      guide adjuvant therapy for resected EHC.

PMID- 25976863
TI  - Association of ABC (HbA1c, blood pressure, LDL-cholesterol) goal attainment with
      depression and health-related quality of life among adults with type 2 diabetes.
AB  - AIMS: To determine the relationship between ABC goal attainment, depression, and
      health-related quality of life (HRQoL) among a national sample of patients with
      type 2 diabetes (T2DM). METHODS: A retrospective, cross-sectional analysis was
      performed examining 808 non-pregnant patients >=20 years old with T2DM from the
      National Health and Nutrition Examination Survey (NHANES) 2007-2012. ABC goals
      were defined as HbA1c<7%, BP<130/80 mm Hg, and LDL-C<100 mg/dL. Patient
      characteristics associated with ABC goal attainment were examined. RESULTS:
      Overall, 23.7% of participants achieved simultaneous ABC goals. Severe depression
      was significantly associated with lower rates of ABC goal attainment compared to
      those with no depression (5.0% vs. 25.4%, p=0.048). ABC goal attainment rates
      were lower among females, Hispanic and non-Hispanic black minority groups, and
      patients with a duration of diabetes over five years, while increased visits with
      health care professionals were significantly associated with meeting all three
      ABC goals for patients with T2DM. CONCLUSIONS: The relationship between
      simultaneous ABC goal attainment, depression and HRQoL is complex. Patients with
      T2DM unable to meet ABC goals may benefit from increased contact with health care
      professionals.

PMID- 25976864
TI  - The diagnostic value of cerebrospinal fluid chemistry results in childhood
      tuberculous meningitis.
AB  - PURPOSE: Cerebrospinal fluid (CSF) hypoglycorrhachia and elevated protein is well
      described in bacterial meningitis, but evidence for its differential diagnostic
      value in tuberculous meningitis (TBM) is lacking. We aimed to assess the
      diagnostic utility of CSF glucose, CSF to serum glucose ratio and CSF protein in
      children with suspected TBM. METHODS: We describe CSF glucose and protein values
      as well as CSF to serum glucose ratios in a prospective evaluation of TBM
      suspects seen at Tygerberg Children's Hospital, Cape Town, South Africa, from
      January 1985 to January 2014. RESULTS: Of 615 TBM suspects, 88 (14%) had
      microbiologically confirmed TBM, 381 (62%) 'probable' TBM and 146 (24%) 'non
      TBM'. Mean absolute CSF glucose concentration was significantly lower in the
      microbiologically confirmed (1.87 +/- 1.15 mmol/L) and 'probable' TBM (1.82 +/-
      1.19 mmol/L) groups compared to non-TBM (3.66 +/- 0.88 mmol/L). A CSF glucose
      concentration of <2.2 mmol/L diagnosed TBM with sensitivity 0.68 and specificity
      0.96. Sensitivity using a CSF to serum glucose ratio of <0.5 was 0.90. Mean CSF
      protein was significantly elevated in the microbiologically confirmed TBM (1.91
      +/- 1.44 g/L) and 'probable' TBM (2.01 +/- 1.49 g/L) groups compared to the non
      TBM (0.31 +/- 0.31 g/L). A CSF protein >1 g/L diagnosed TBM with sensitivity 0.78
      and specificity 0.94. CONCLUSION: Absolute CSF glucose values of <2.2 mmol/L and
      protein values of >1 g/L differentiated between TBM and non-bacterial meningitis
      with good specificity, although sensitivity was poor. A CSF to serum glucose
      ratio is more informative than the absolute value.

PMID- 25976865
TI  - Endoscopic transnasal repair of cerebrospinal fluid leaks with and without an
      encephalocele in pediatric patients: from infants to children.
AB  - PURPOSE: The diagnosis and management of pediatric cerebrospinal fluid (CSF) leak
      and encephalocele are challenging. The current study aimed to identify patient
      characteristics, review operative techniques, and evaluate the efficacy and
      safety of endoscopic endonasal repair in a pediatric population. METHODS: We
      retrospectively reviewed the records of pediatric patients who underwent
      transnasal endoscopic repair of CSF leak with or without a meningocele or an
      encephalocele at Beijing Tongren Hospital, Capital Medical University, between
      July 2003 and May 2014. All patients had preoperative radiological evaluations
      and underwent endoscopic endonasal repair of their skull base defects. RESULTS:
      Altogether, 23 children (mean age 7.0 years) underwent the procedures. Sixteen
      cases were congenital, and 7 patients had trauma history. The herniations or
      defects included meningoencephaloceles in 15 cases, meningoceles in 4 cases, and
      CSF leak in 4 cases (2 patients had bilateral leaks). The leak or herniation
      sites were ethmoid roof in 10 patients (one was bilateral), cribriform plate in
      5, lateral to the foramen cecum in 3, posterior wall of the frontal sinus in 1,
      sphenoid sinus in 2, lateral recess of the sphenoid sinus in 1, and sella turcica
      base in 2. All subjects had favorable clinical outcomes without recurrence during
      a follow-up of 6-123 months (mean 61.1 months). CONCLUSIONS: The endoscopic
      endonasal approach was the preferred method for repairing CSF leaks with or
      without an encephalocele in pediatric patients. Compared to traditional
      operations, this endoscopic procedure is minimally invasive, efficient, and safe.

PMID- 25976866
TI  - Patterns and treatment of neck metastases in patients with salivary gland
      cancers.
AB  - BACKGROUND: Management of the neck in patients with salivary gland cancer is
      controversial. This study aimed to identify clinicopathologic characteristics
      associated with regional metastases and regional recurrence in patients with
      salivary gland carcinoma. METHODS: Of 363 study patients, 51 underwent
      therapeutic neck dissection (TND) and 312 underwent either elective neck
      dissection (END, n = 110) or no neck dissection (NoND, n = 202). Univariate and
      multivariate analyses were performed to identify clinicopathologic
      characteristics associated with regional metastases and recurrence. RESULTS:
      Pathologic neck metastases were identified in 17/110 (15.5%) END patients and
      neck recurrence was identified in 5/202 (2.5%) NoND patients. Histologic grade (P
      < 0.001), tumor site (P = 0.008), and lymphovascular invasion (P < 0.001) were
      independent risk factors for neck metastases. Nodal metastases were more common
      in high-grade tumors (P < 0.001), at levels I-III in END patients and levels I-V
      in TND patients. Multivariate analyses identified histologic grade (P = 0.020),
      clinical N2 classification (P = 0.007), and extranodal extension (P = 0.005) as
      independent factors for regional recurrence after treatment. CONCLUSIONS:
      Patients with high-grade cancers should receive END involving levels I-III,
      whereas patients with node-positive salivary cancers should receive comprehensive
      TND involving all levels (I-V).

PMID- 25976867
TI  - In reference to "Association of face-to-face handoffs and outcomes of
      hospitalized internal medicine patients".

PMID- 25976869
TI  - Assessing treatment effects with surrogate survival outcomes using an internal
      validation subsample.
AB  - BACKGROUND: In studies with surrogate outcomes available for all subjects and
      true outcomes available for only a subsample, survival analysis methods are
      needed that incorporate both endpoints in order to assess treatment effects.
      METHODS: We develop a semiparametric estimated likelihood method for the
      proportional hazards model with discrete time data and a binary covariate of
      interest. Our proposed method allows for real-time validation of surrogate
      outcomes and flexible censoring mechanisms. RESULTS: Our proposed estimator is
      consistent and asymptotically normal. Through numerical studies, we showed that
      our proposed method for estimating a covariate effect is unbiased compared to the
      naive estimator that uses only surrogate endpoints and is more efficient with
      moderate missingness compared to the complete-case estimator that uses only true
      endpoints. We further demonstrated the advantages of our proposed method in
      comparison with existing approaches when there is real-time validation. We also
      illustrated the use of our proposed method by estimating the effect of gender on
      time to detection of Alzheimer's disease using data from the Alzheimer's Disease
      Neuroimaging Initiative. CONCLUSION: The proposed method is able to account for
      the uncertainty of surrogate outcomes using a validation subsample of true
      outcomes in estimating a binary covariate effect. The proposed estimator can
      outperform standard semiparametric survival analysis methods and can therefore
      save on costs of a trial or improve power in detecting treatment effects.

PMID- 25976870
TI  - Tailoring Plasmonic Enhanced Upconversion in Single NaYF4:Yb(3+)/Er(3+)
      Nanocrystals.
AB  - By using silver nanoplatelets with a widely tunable localized surface plasmon
      resonance (LSPR), and their corresponding local field enhancement, here we show
      large manipulation of plasmonic enhanced upconversion in NaYF4:Yb(3+)/Er(3+)
      nanocrystals at the single particle level. In particular, we show that when the
      plasmonic resonance of silver nanolplatelets is tuned to 656 nm, matching the
      emission wavelength, an upconversion enhancement factor ~5 is obtained. However,
      when the plasmonic resonance is tuned to 980 nm, matching the nanocrystal
      absorption wavelength, we achieve an enhancement factor of ~22 folds. The precise
      geometric arrangement between fluorescent nanoparticles and silver nanoplatelets
      allows us to make, for the first time, a comparative analysis between
      experimental results and numerical simulations, yielding a quantitative agreement
      at the single particle level. Such a comparison lays the foundations for a
      rational design of hybrid metal-fluorescent nanocrystals to harness the
      upconversion enhancement for biosensing and light harvesting applications. 

PMID- 25976868
TI  - Stem cell mobilization and autologous stem cell transplantation after
      pretreatment with bendamustine, prednisone and bortezomib (BPV) in newly
      diagnosed multiple myeloma.
AB  - INTRODUCTION: Reliable information on stem cell toxicity and mobilization of stem
      cells for autologous stem cell transplantation (SCT) after induction treatment
      with a combination of bendamustine, prednisone and bortezomib (BPV) is missing.
      MATERIALS AND METHODS: A retrospective analysis of peripheral blood stem cell
      mobilization and autologous SCT was performed in 35 patients with MM who had
      received at least one cycle of a BPV-induction therapy consisting of bendamustine
      60 mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 and
      prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014.
      The mobilization regimen consisted of cyclophosphamide 4 g/m(2) and G-CSF (2 * 5
      MUg/kg). Apheresis was started as soon as peripheral CD34(+) counts exceeded 20 *
      10(6)/L with a harvest target of 8 * 10(6) CD34(+)/kg. The minimal accepted
      target was 2 * 10(6) CD34(+)/kg. The transplantation conditioning therapy
      consisted of melphalan 200 mg/m(2). RESULTS: A median number of two (range 1-5)
      BPV cycles were given. The majority of patients (n = 31, 89 %) responded with two
      sCR, five nCR, 11 VGPR and 13 PR after BPV induction. Three patients had MR, and
      one SD. Stem cell mobilization and harvest were successful in all patients. In 19
      of 35 patients (54 %), a single apheresis was sufficient to reach the target. The
      median number of aphereses was one (range 1-4), and the median CD34(+) cell
      count/kg was 13.5 (range 3.2-33.1)  * 106. All patients received an autologous
      SCT. Engraftment was successful in 34 of 35 patients. The median time to a
      leukocyte count >l * 10(9)/L was 11 days, and the time to untransfused platelet
      count of >50 * 10(9)/L was 13 days. Thirty-four patients (97 %) responded after
      the autologous SCT with 11 sCR, two CR, seven nCR, seven VGPR and seven PR. The
      progression-free survival at 18 months was 87 %, and overall survival was 92 %.
      CONCLUSION: Stem cell mobilization and autologous SCT are feasible in MM patients
      who have received BPV-induction therapy .

PMID- 25976871
TI  - Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and
      multifocal motor neuropathy.
AB  - Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are
      efficacious treatment in chronic inflammatory demyelinating polyneuropathy
      [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS
      weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and
      Dyck/Rankin score provided reliable measures to detect and scale abnormality and
      reflect change; they are therefore ideal for office management of response-based
      immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late
      therapeutic response (>= one-fourth were in remission or had recovered) was
      demonstrated in CIDP. In MMN only an early improvement with late non-significant
      worsening was observed. The difference in immunotherapy response supports a
      fundamental difference between CIDP (immune attack on Schwann cells and myelin)
      and MMN (attack on nodes of Ranvier and axons).

PMID- 25976873
TI  - Abstracts for GISMAD, May 7-9, 2015, Rome, Italy.

PMID- 25976872
TI  - Dissection of the style's response to pollination using transcriptome profiling
      in self-compatible (Solanum pimpinellifolium) and self-incompatible (Solanum
      chilense) tomato species.
AB  - BACKGROUND: Tomato (Solanum lycopersicum) self-compatibility (SC) is defined as
      self-pollen tubes that can penetrate their own stigma, elongate in the style and
      fertilize their own ovules. Self-incompatibility (SI) is defined as self-pollen
      tubes that are prevented from developing in the style. To determine the influence
      of gene expression on style self-pollination, a transcriptome-wide comparative
      analysis of SC and SI tomato unpollinated/pollinated styles was performed using
      RNA-sequencing (RNA-seq) data. RESULTS: Transcriptome profiles of 24-h
      unpollination (UP) and self-pollination (P) styles from SC and SI tomato species
      were generated using high-throughput next generation sequencing. From the
      comparison of SC self-pollinated and unpollinated styles, 1341 differentially
      expressed genes (DEGs) were identified, of which 753 were downregulated and 588
      were upregulated. From the comparison of SI self-pollinated and unpollinated
      styles, 804 DEGs were identified, of which 215 were downregulated and 589 were
      upregulated. Nine gene ontology (GO) terms were enriched significantly in SC and
      78 GO terms were enriched significantly in SI. A total of 105 enriched Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways were identified in SC and 80
      enriched KEGG pathways were identified in SI, among which "Cysteine and
      methionine metabolism pathway" and "Plant hormone signal transduction pathway"
      were significantly enriched in SI. CONCLUSIONS: This study is the first global
      transcriptome-wide comparative analysis of SC and SI tomato
      unpollinated/pollinated styles. Advanced bioinformatic analysis of DEGs uncovered
      the pathways of "Cysteine and methionine metabolism" and "Plant hormone signal
      transduction", which are likely to play important roles in the control of pollen
      tubes growth in SI species.

PMID- 25976875
TI  - Contrasting Effects of Farmyard Manure (FYM) and Compost for Remediation of Metal
      Contaminated Soil.
AB  - We investigated effect of farm yard manure (FYM) and compost applied to metal
      contaminated soil at rate of 1% (FYM-1, compost-1), 2% (FYM-2, compost-2), and 3%
      (FYM-3, compost-3). FYM significantly (P < 0.001) increased dry weights of shoots
      and roots while compost increased root dry weight compared to control. Amendments
      significantly increased nickel (Ni) in shoots and roots of maize except compost
      applied at 1%. FYM-3 and -1 caused maximum Ni in shoots (11.42 mg kg(-1)) and
      roots (80.92 mg kg(-1)), respectively while compost-2 caused maximum Ni (14.08 mg
      kg(-1)) and (163.87 mg kg(-1)) in shoots and roots, respectively. Plants grown in
      pots amended with FYM-2 and compost-1 contained minimum Cu (30.12 and 30.11 mg
      kg(-1)) in shoots, respectively. FYM-2 and compost-2 caused minimum zinc (Zn)
      (59.08 and 66.0 mg kg(-1)) in maize shoots, respectively. FYM-2 caused minimum Mn
      in maize shoots while compost increased Mn in shoots and roots compared to
      control. FYM and compost increased the ammonium bicarbonate diethylene triamine
      penta acetic acid (AB-DTPA) extractable Ni and Mn in the soil and decreased Cu
      and Zn. Lower remediation factors for all metals with compost indicated that
      compost was effective to stabilize the metals in soil compared to FYM.

PMID- 25976874
TI  - Social Relationships and Sleep Quality.
AB  - BACKGROUND: The quality of social relationships and social support appears to be
      associated with physical health outcomes and sleep quality. Almost all previous
      research in this area focuses on positive aspects of relationships. PURPOSE: The
      present study thus intended to examine the links between supportive, aversive,
      ambivalent, and indifferent network ties and sleep quality. METHODS: Relationship
      data, Pittsburgh Sleep Quality Index (PSQI)-assessed sleep quality, and
      depression were examined in 175 middle-aged and older adults. RESULTS: Consistent
      with hypotheses, supportive ties were positively related to sleep quality, while
      aversive ties predicted worse sleep quality, associations that were primarily
      seen for close relationships. Ambivalent and indifferent ties were not
      significant predictors of sleep quality. Importantly, depression was found to
      mediate the link between relationship quality and sleep quality. CONCLUSIONS:
      These data suggest the more specific types of social relationships that may be
      linked to poor sleep quality and that depression appears to underlie these
      associations.

PMID- 25976876
TI  - An Abandoned Copper Mining Site in Cyprus and Assessment of Metal Concentrations
      in Plants and Soil.
AB  - Mining is an important source of metal pollution in the environment and abandoned
      mines are extremely restricted habitats for plants. Some plant species growing on
      metalliferous soils around mine tailings and spoil-heaps are metal-tolerant and
      accumulate high concentrations of metals. In this investigation, we aimed to
      perform a research in the CMC-abandoned copper mining area in Lefke-North Cyprus
      to assess the recent metal pollution in soil and plant systems. We collected 16
      soil samples and 25 plant species from 8 localities around the vicinity of
      tailing ponds. Some concentrations of metals in soil samples varied from 185 to
      1023 mg kg(-1) Cu, 15.2 to 59.2 mg kg(-1) Ni, 2.3 to 73.6 mg kg(-1) Cd and metals
      for plants ranged from 0.135 to 283 mg kg(-1) Cu, 0.26 to 31.2 mg kg(-1) Ni,
      0.143 to 277 mg kg(-1) Cd. Atriplex semibaccata, Acacia cyanophylla, Erodium
      spp., Inula viscosa, Juncus sp., Oxalis pes-caprea, Pistacia lentiscus, Senecio
      vulgaris and Tragopogon sinuatus accumulated higher concentrations. BCF for
      Atriplex semibaccata was found very high, for this reason this plant can
      tentatively be considered as a hyperaccumulator of Cu and Cd, but it needs
      further investigation for its potential in phytoremediation.

PMID- 25976877
TI  - Use of Energy Crop (Ricinus communis L.) for Phytoextraction of Heavy Metals
      Assisted with Citric Acid.
AB  - Ricinus communis L. is a bioenergetic crop with high-biomass production and
      tolerance to cadmium (Cd) and lead (Pb), thus, the plant is a candidate crop for
      phytoremediation. Pot experiments were performed to study the effects of citric
      acid in enhancing phytoextraction of Cd/Pb by Ricinus communis L. Citric acid
      increased Cd and Pb contents in plant shoots in all treatments by about 78% and
      18-45%, respectively, at the dosage of 10 mM kg(-1) soil without affecting
      aboveground biomass production. Addition of citric acid reduced CEC, weakened
      soil adsorption of heavy metals and activated Cd and Pb in soil solutions. The
      acid-exchangeable fraction (BCR-1) of Pb remained lower than 7% and significantly
      increased with citric acid amendment. Respective increases in soil evaluation
      index induces by 14% and 19% under the Cd1Pb50 and Cd1Pb250 treatments upon
      addition of citric acid resulted in soil quality improvement. Ricinus communis L.
      has great potential in citric acid-assisted phytoextraction for Cd and Pb
      remediation.

PMID- 25976878
TI  - Mini-review of knowledge gaps in salt tolerance of plants applied to willows and
      poplars.
AB  - Salt tolerance of agricultural crops has been studied since the 1940, but
      knowledge regarding salt tolerance of woody crops is still in its initial phase.
      Salt tolerance of agricultural crops has been expressed as the yield decrease due
      to a certain salt concentration within the root zone as compared to a non-saline
      control. The most well-known plant response curve to salinity has been a piece
      wise linear regression relating crop yield to root zone salinity. This method
      used the hypothesis that crops tolerate salt up to a threshold after which their
      yield decreases approximately linearly. Critique to this method included its lack
      of sensitivity to dynamic factors such as weather conditions. As a result, other
      classification indices have been developed, but none is as well accepted as the
      threshold-slope model. In addition to a mini-review of the key salt tolerance
      studies, our objective was to classify salt tolerance levels of poplars and
      willows. Initial classification showed that salt tolerance of these genera ranged
      from sensitive to moderately tolerant. 

PMID- 25976879
TI  - Remediation and Safe Production of cd Contaminated Soil Via Multiple Cropping
      Hyperaccumulator Solanum nigrum L. and Low Accumulation Chinese Cabbage.
AB  - Multiple crop experiment of hyperaccumulator Solanum nigrum L. with low
      accumulation Chinese cabbage Fenyuanxin 3 were conducted in a cadmium (Cd)
      contaminated vegetable field. In the first round, the average removal rate of S.
      nigrum to Cd was about 10% without assisted phytoextraction reagent addition for
      the top soil (0-20 cm) with Cd concentration at 0.53-0.97 mg kg(-1) after its
      grew 90 days. As for assisted phytoextraction reagent added plots, efficiency of
      Cd remediation might reach at 20%. However, in the second round, Cd concentration
      in Chinese cabbage was edible, even in the plots with assisted phytoextraction
      reagent added. Thus, multiple cropping hyperaccumulator with low accumulation
      crop could normally remediate contaminated soil and produce crop (obtain economic
      benefit) in one year, which may be one practical pathway of phytoremediating
      heavy metal contaminated soil in the future.

PMID- 25976880
TI  - Phytotoxicity of citric acid and Tween(r) 80 for potential use as soil amendments
      in enhanced phytoremediation.
AB  - Enhanced phytoremediation adding biodegradable amendments like low molecular
      weight organic acids and surfactants is an interesting area of current research
      to overcome the limitation that represents low bioavailability of pollutants in
      soils. However, prior to their use in assisted phytoremediation, it is necessary
      to test if amendments per se exert any toxic effect to plants and to optimize
      their application mode. In this context, the present study assessed the effects
      of citric acid and Tween(r) 80 (polyethylene glycol sorbitan monooleate) on the
      development of alfalfa (Medicago sativa) plants, as influenced by their
      concentration and frequency of application, in order to evaluate the feasibility
      for their future use in enhanced phytoremediation of multi-contaminated soils.
      The results showed that citric acid negatively affected plant germination, while
      it did not have any significant effect on biomass or chlorophyll content. In
      turn, Tween(r) 80 did not affect plant germination and showed a trend to increase
      biomass, as well as it did not have any significant effect on chlorophyll levels.
      M. sativa appeared to tolerate citric acid and Tween(r) 80 at the tested
      concentrations, applied weekly. Consequently, citric acid and Tween(r) 80 could
      potentially be utilized to assist phytoremediation of contaminated soils
      vegetated with M. sativa. 

PMID- 25976881
TI  - Removal of Chlorpyrifos by Water Hyacinth (Eichhornia crassipes) and the Role of
      a Plant-Associated Bacterium.
AB  - The objective of this research was to study the efficiency of water hyacinth
      (Eichhornia crassipes) and the role of any plant-associated bacteria in removing
      chlorpyrifos from water. The relative growth rate (RGR) of E. crassipes in the
      presence of 0.1 mg/L chlorpyrifos was not significantly different from that in
      its absence and only slightly decreased at concentrations of 0.5 and 1.0 mg/L by
      ~1.1- and ~1.2-fold, respectively, with an observed dry weight based RGRDW for E.
      crassipes of 0.036-0.041 mg/g/d. The removal rate constants of chlorpyrifos in
      the absence of plants were low at 3.52, 2.29 and 1.84 h(-1) for concentrations of
      0.1, 0.5 and 1.0 mg/L, respectively, but were some 3.89- to 4.87-fold higher in
      the presence of E. crassipes. Chlorpyrifos removal was markedly facilitated by
      the presence of a root-associated bacterium, preliminarily identified as
      Acinetobacter sp. strain WHA. The interaction of E. crassipes and Acinetobacter
      sp. strain WHA provide an efficient and ecological alternative to accelerate the
      removal and degradation of chlorpyrifos pollution from aquatic systems including
      wastewater.

PMID- 25976882
TI  - Phytodegradation of Ethanolamines by Cyperus alternifolius: Effect of Molecular
      Size.
AB  - Our screening of plants showed that Cyperus alternifolius (Umbrella papyrus) had
      the highest efficiency removal in real wastewater containing monoethanolamine
      higher than Echinodorus cordifolius (Creeping Burrhead), Thalia geniculata
      (Alligator Flag), Acorus calamus (Sweet Flag), and Dracaena sanderiana (Lucky
      Bamboo). Therefore, this research studied the degradation of monoethanolamine
      (MEA), diethanolamine (DEA), and triethanolamine (TEA) by C. alternifolius.
      Plants could degrade TEA into DEA, then into MEA, and then further into acetic
      acid. The accumulation of ethanolamines was found mainly in plant stems, which
      had the highest biomass. This demonstrated that the molecular size is closely
      related to a diffusion coefficient that affects the removal rate through plant
      bodies. A smaller molecular weight-MEA (MW = 61.08 g mol(-1))-was taken up the
      fastest, followed by DEA (MW = 105.14 g mol(-1)) and TEA (MW = 149.19 g mol(-1)),
      the highest molecular weight. The plants' toxicity when exposed to ethanolamines
      elucidated that MEA had the highest toxicity, followed by DEA and TEA. In
      addition, the application of C. alternifolius in monoethanolamine-contaminated
      wastewater revealed that plant could completely uptake MEA at day 5 from an
      initial MEA concentration of 18 mM. The result indicated that C. alternifolius
      has the potential to remove ethanolamines and can be applied to ethanolamine
      contaminated wastewater.

PMID- 25976883
TI  - Accumulation of Hydrocarbons by Maize (Zea mays L.) in Remediation of Soils
      Contaminated with Crude Oil.
AB  - This study has investigated the use of screened maize for remediation of soil
      contaminated with crude oil. Pots experiment was carried out for 60 days by
      transplanting maize seedlings into spiked soils. The results showed that certain
      amount of crude oil in soil (<=2 147 mg.kg(-1)) could enhance the production of
      shoot biomass of maize. Higher concentration (6 373 mg.kg(-1)) did not
      significantly inhibit the growth of plant maize (including shoot and root).
      Analysis of plant shoot by GC-MS showed that low molecular weight polycyclic
      aromatic hydrocarbons (PAHs) were detected in maize tissues, but PAHs
      concentration in the plant did not increase with higher concentration of crude
      oil in soil. The reduction of total petroleum hydrocarbon in planted soil was up
      to 52.21-72.84%, while that of the corresponding controls was only 25.85-34.22%
      in two months. In addition, data from physiological and biochemical indexes
      demonstrated a favorable adaptability of maize to crude oil pollution stress.
      This study suggested that the use of maize (Zea mays L.) was a good choice for
      remediation of soil contaminated with petroleum within a certain range of
      concentrations.

PMID- 25976884
TI  - Organophosphorus and Organochlorine Pesticides Bioaccumulation by Eichhornia
      crassipes in Irrigation Canals in an Urban Agricultural System.
AB  - A natural wetland in Mexico City Metropolitan Area is one of the main suppliers
      of crops and flowers, and in consequence its canals hold a high concentration of
      organochlorine (OC) and organophosphorus (OP) pesticides. There is also an
      extensive population of water hyacinth (Eichhornia crassipes), which is
      considered a plague; but literature suggests water hyacinth may be used as a
      phytoremediator. This study demonstrates bioaccumulation difference for the OC in
      vivo suggesting their bioaccumulation is ruled by their log K(ow), while all the
      OP showed bioaccumulation regardless of their log K(ow). The higher
      bioaccumulation factors (BAF) of the accumulated OC pesticides cannot be
      explained by their log K(ow), suggesting that the OC pesticides may also be
      transported passively into the plant. Translocation ratios showed that water
      hyacinth is an accumulating plant with phytoremediation potential for all
      organophosphorus pesticides studied and some organochlorine pesticides. An
      equation for free water surface wetlands with floating macrophytes, commonly used
      for the construction of water-cleaning wetlands, showed removal of the pesticides
      by the wetland with room for improvement with appropriate management.

PMID- 25976885
TI  - Potential of Mauritius Hemp (Furcraea gigantea Vent.) for the Remediation of
      Chromium Contaminated Soils.
AB  - The present study was conducted to evaluate the ability of a high biomass
      producing, drought tolerant succulent plant Mauritius hemp (Furcraea gigantea
      Vent.) for its tolerance to different levels of Cr (0, 25, 50, 100 and 200 mg Cr
      kg soil(-1)) and its potential for phytoremediation purposes. Based on the data
      on inhibition of the growth of plants with Cr, tolerance index and grade of
      growth inhibition, it was observed that the plant could tolerate up to 50 mg Cr
      kg (-1) soil. Absorption of Cr from soil to plant and its translocation into
      plant tissues were discussed in terms of bio concentration factor (BCF), transfer
      factor (TF), and translocation efficiency (TE%). Cr was mainly accumulated in the
      roots and exclusion of Cr was found to be the principal physiological tolerance
      mechanism followed by a marked increase in proline, ascorbic acid, total free
      amino acids in the leaf tissue and malic acid in the rhizosphere samples to
      counter Cr stress. Based on the tissue concentration of Cr (< 300 MUg g(-1) in
      the leaves and TF<1), it was concluded that, Furcraea gigantea could not be
      considered a hyperaccumulator and therefore unsuitable for phytoextraction of Cr.
      Nevertheless, Furcraea gigantea could be a suitable candidate for
      phytostablization of Cr contaminated soils.

PMID- 25976887
TI  - The use of the lactone motif in chemical communication.
AB  - A wide variety of organisms communicate via the chemical channel using small
      molecules. A structural feature quite often found is the lactone motif. In the
      present paper, the current knowledge on such lactones will be described,
      concentrating on the structure, chemistry, function, biosynthesis and synthesis
      of these compounds. Lactone semiochemicals from insects, vertebrates and
      bacteria, which this article will focus on, are particularly well investigated.
      In addition, some ideas on the advantageous use of lactones as volatile signals,
      which promoted their evolutionary development, will be discussed.

PMID- 25976886
TI  - Binding of RDX to Cell Wall Components of Pinus sylvestris and Picea glauca and
      Three-Year Mineralisation Study of Tissue-Associated RDX Residues.
AB  - Contamination of soils with the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine
      (RDX, Research Department Explosive) as a result of military applications is a
      large-area problem globally. Since coniferous trees dominate the vegetation of
      large areas of military land in Central Europe, particularly in Germany, the long
      term fate of (14)C-RDX in the conifers Scots pine and Dwarf Alberta spruce was
      studied. Acetic acid was the most effective solvent for the removal of
      extractable RDX residues from homogenates of RDX-laden tree material (85%, 80-90%
      and 64-80% for roots, wood and needles, respectively). On average, only a fifth
      of RDX-derived (14)C was bound in non-extractable residues (NER). Within the main
      cell wall compartments, lignin was the dominant binding site for NER (needles: 32
      62%; roots: 38-42%). Hemicellulose (needles: 11-18%; roots: 6-11%) and cellulose
      (needles: 12-24%; roots: 1-2%) were less involved in binding and a considerable
      proportion of NER (needles: 15-24%; roots: 59-51%) was indigestible. After three
      year incubation in rot chambers, mineralisation of tree-associated (14)C-RDX to
      (14)CO2 clearly dominated the mass balance in both tree species with 48-83%. 13
      33% of (14)C-RDX-derived radioactivity remained in an unleachable form and the
      remobilisation by water leaching was negligible (< 2%). 

PMID- 25976890
TI  - Editorial: overhauling the entire system of care to improve cardiac surgery
      outcomes.

PMID- 25976888
TI  - The impact of taxane-based preoperative chemotherapy in gastroesophageal signet
      ring cell adenocarcinomas.
AB  - The benefit of preoperative chemotherapy in resectable gastroesophageal
      adenocarcinomas was not observed in signet ring cell subtype. However, the
      potential interest of taxane-based preoperative chemotherapy on this subtype is
      still an unresolved issue. Nineteen patients with localized signet ring cell
      adenocarcinomas received taxane-based regimens, and 17 patients underwent
      surgery. Complete resection was achieved in 80 %, and median overall survival was
      40.8 months (95 % confidence interval (CI), 20.2-not reached). Even though one
      patient achieved a complete pathological response, seven patients had an
      upstaging of their tumors at surgery. The potential benefits of taxane-based
      chemotherapy seem to be limited to a reduced number of patients.

PMID- 25976891
TI  - Journey to top performance: a multipronged quality improvement approach to
      reducing cardiac surgery mortality.
AB  - BACKGROUND: In 2006, leadership at Long Island Jewish Medical Center (New Hyde
      Park, New York) noted significantly higher cardiac surgery mortality rates for
      isolated valve and valve/coronary artery bypass graft procedures compared to the
      New York State Department of Health's Cardiac Surgery Reporting System statewide
      average. METHODS: Long Island Jewish Medical Center, a 583-bed nonprofit,
      tertiary care teaching hospital, is one of the clinical and academic hubs of
      North Shore-LIJ Health System. Senior leadership launched an evaluation of the
      cardiac surgery program to determine why cardiac surgery mortality rates were
      higher than expected. As a result, the cardiac surgery program was redesigned,
      and interventions were implemented related to preoperative care, intraoperative
      monitoring, postoperative care, and the cardiac surgery quality management
      program. RESULTS: According to the most recent New York State Department of
      Health reporting period (2009-2011), Long Island Jewish Medical Center had the
      lowest risk-adjusted mortality rate in New York State for adult patients
      undergoing surgeries to repair or replace heart valves and for adult patients in
      need of valve/coronary artery bypass graft surgery. The medical center has
      sustained significantly lower mortality rates compared to the statewide average
      for the past three cardiac surgery reporting periods. CONCLUSIONS: Cardiac
      surgery mortality rates can be significantly reduced and sustained below
      comparative norms when the organization is committed to clinical excellence and
      quality and is involved in continuously assessing organizational performance. The
      evaluation launched at Long Island Jewish Medical Center led to the redesign of
      the cardiac surgery program and prompted widespread improvement efforts and
      cultural change across the entire organization.

PMID- 25976893
TI  - Editorial: spending the coins of knowledge on safer health care.

PMID- 25976892
TI  - Rethinking critical care: decreasing sedation, increasing delirium monitoring,
      and increasing patient mobility.
AB  - BACKGROUND: Sedation management, delirium monitoring, and mobility programs have
      been addressed in evidence-based critical care guidelines and care bundles, yet
      implementation in the ICU remains variable. As critically ill patients occupy
      higher percentages of hospital beds in the United States and beyond, it is
      increasingly important to determine mechanisms to deliver better care. The
      Institute for Healthcare Improvement's Rethinking Critical Care (IHI-RCC) program
      was established to reduce harm of critically ill patients by decreasing sedation,
      increasing monitoring and management of delirium, and increasing patient
      mobility. Case studies of a convenience sample of five participating
      hospitals/health systems chosen in advance of the determination of their clinical
      outcomes are presented in terms of how they got started and process improvements
      in sedation management, delirium management, and mobility. METHODS: The IHI-RCC
      program involved one live case study and five iterations of an in-person seminar
      in a 33-month period (March 2011-November 2013) that emphasized interdisciplinary
      teamwork and culture change. RESULTS: Qualitative descriptions of the changes
      tested at each of the five case study sites demonstrate improvements in teamwork,
      processes, and reliability of daily work. Improvement in ICU length of stay and
      length of stay on the ventilator between the pre- and postimplementation periods
      varied from slight to substantial. CONCLUSION: Changing critical care practices
      requires an interdisciplinary approach addressing cultural, psychological, and
      practical issues. The key lessons of the IHI-RCC program are as follows: the
      importance of testing changes on a small scale, feeding back data regularly and
      providing sufficient education, and building will through seeing the work in
      action.

PMID- 25976894
TI  - Using a quantitative risk register to promote learning from a patient safety
      reporting system.
AB  - BACKGROUND: Patient safety reporting systems are now used in most health care
      delivery organizations. These systems, such as the one in use at Virginia Mason
      (Seattle) since 2002, can provide valuable reports of risk and harm from the
      front lines of patient care. In response to the challenge of how to quantify and
      prioritize safety opportunities, a risk register system was developed and
      implemented. METHODS: Basic risk register concepts were refined to provide a
      systematic way to understand risks reported by staff. The risk register uses a
      comprehensive taxonomy of patient risk and algorithmically assigns each patient
      safety report to 1 of 27 risk categories in three major domains (Evaluation,
      Treatment, and Critical Interactions). For each category, a composite score was
      calculated on the basis of event rate, harm, and cost. The composite scores were
      used to identify the "top five" risk categories, and patient safety reports in
      these categories were analyzed in greater depth to find recurrent patterns of
      risk and associated opportunities for improvement. RESULTS: The top five
      categories of risk were easy to identify and had distinctive "profiles" of rate,
      harm, and cost. The ability to categorize and rank risks across multiple
      dimensions yielded insights not previously available. These results were shared
      with leadership and served as input for planning quality and safety initiatives.
      This approach provided actionable input for the strategic planning process, while
      at the same time strengthening the Virginia Mason culture of safety. CONCLUSIONS:
      The quantitative patient safety risk register serves as one solution to the
      challenge of extracting valuable safety lessons from large numbers of incident
      reports and could profitably be adopted by other organizations.

PMID- 25976895
TI  - Leveraging evidence across the care continuum.

PMID- 25976897
TI  - Trends in survival after cancer diagnosis among HIV-infected individuals between
      1992 and 2009. Results from the FHDH-ANRS CO4 cohort.
AB  - Although the decline in cancer mortality rates with the advent of combination
      antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained
      by a decrease in cancers incidence, we looked here if improved survival after
      cancer diagnosis could also contribute to this decline. Survival trends were
      analyzed for most frequent cancers in the HIV-infected population followed in the
      French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral
      Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and
      Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year
      Kaplan-Meier survival rates were estimated for four periods: 1992-1996, 1997
      2000, 2001-2004 and 2005-2009. Cox proportional hazard models were used to
      compare survival across the periods, after adjustment for confounding factors.
      For 2001-2004, survival was compared to the general population after
      standardization on age and sex. Between the pre-cART (1992-1996) and early-cART
      (1997-2000) periods, survival improved after KS, NHL, HL and anal cancer and
      remained stable after lung and liver cancers. During the cART era, 5-year
      survival improved after visceral and non-visceral KS, NHL, HL and liver cancer,
      being 83, 92, 65, 87 and 19% in 2005-2009, respectively, and remained stable
      after lung and anal cancers, being 16 and 65%, respectively. Compared with the
      general population, survival in HIV-infected individuals in 2001-2004 was poorer
      for hematological malignancies and similar for solid tumors. For hematological
      malignancies, survival continues to improve after 2004, suggesting that the gap
      between the HIV-infected and general populations will close in the future. 

PMID- 25976898
TI  - Photo quiz: not-so-humongous fungus or an imposter? Actinomyces meyeri Sinusitis.

PMID- 25976899
TI  - Confused by Weissella confusa Bacteremia.

PMID- 25976901
TI  - Retraction for teramoto et Al., molecular epidemiology of a hepatitis C virus
      outbreak in a leprosy sanatorium in Japan.

PMID- 25976900
TI  - Reply to "Confused by Weissella confusa Bacteremia".

PMID- 25976904
TI  - Asymptomatic ventricular premature depolarizations are not necessarily benign.
AB  - AIMS: Most patients with idiopathic ventricular premature depolarizations (VPDs)
      complain of symptoms related to this arrhythmia, but some patients are
      asymptomatic even with a high VPD burden. Our understanding of the relationship
      between symptoms and cardiomyopathy related to this arrhythmia remains limited.
      METHODS AND RESULTS: We evaluated 801 subjects (381 men; mean age, 55 +/- 17
      years) who visited our outpatient clinic. All subjects were diagnosed with
      frequent VPDs (1% or >1000 beats/day). The patients were divided into two groups
      according to the presence or absence of typical VPD symptoms (palpitations or
      skipped beats during VPDs): symptomatic patients (n = 455) and asymptomatic
      patients (n = 346). Clinical and electrocardiogram parameters were compared
      between these two groups. In the symptomatic group, palpitations were the most
      frequent symptom (91%). Daily VPD burden (P = 0.90) and electrocardiogram
      parameters (P>0.05) did not differ significantly between groups. The incidence of
      frequent VPDs with left ventricular dysfunction was significantly higher in the
      asymptomatic group (symptomatic patients, 3.0%; asymptomatic patients, 10.5%; P <
      0.001). CONCLUSION: The absence of typical VPD-related symptoms may be a risk
      factor for cardiomyopathy and be associated with an adverse outcome.

PMID- 25976905
TI  - Assessment of a structured management pathway for patients referred to the
      Emergency Department for syncope: results in a tertiary hospital.
AB  - AIMS: High hospitalization rates (39-58% in the literature) of patients admitted
      to Emergency Department (ED) for transient loss of consciousness (T-LOC)
      suspected for syncope are still an unresolved issue. The presence of an
      Observation Unit has reduced hospital admissions and the duration of
      hospitalization in controlled studies, and a Syncope Unit (SU) in the hospital
      may reduce hospitalization and increase the number of diagnoses in patients with
      T-LOC. We assessed the effect of a structured organization on hospitalization
      rate and outcome. METHODS AND RESULTS: Consecutive patients referred to the ED
      for a T-LOC of a suspected syncopal nature as the main diagnosis were included.
      The ED physician was trained to choose between: hospital admission (directly or
      after short observation); discharge after short (<48-h) observation; discharge on
      a fast track to the SU; and direct discharge without any further diagnostics.
      From January to June 2010, 362 patients were evaluated in the ED: 29% were
      admitted, 20% underwent short observation in the ED, 20% were referred to the SU,
      and 31% were directly discharged. Follow-up data were available on 295 patients
      who were discharged alive: of these, 1 (0.3%) previously hospitalized patient
      died within 30 days and 16 (5.4%) died within 1 year. Death rates were 12.9, 3.3,
      0, and 2.5% among admitted, observation, SU, and ED-discharged patients,
      respectively. No death could be directly attributed to T-LOC. Re-admission within
      1 year for any cause occurred in 72 (24%) patients; re-admission rates were 45.9,
      19.3, 11.5, and 18.0% among admitted, observation, SU, and ED-discharged
      patients, respectively. CONCLUSIONS: The availability of short observation and a
      SU seems to reduce the hospitalization rate compared with previous reported
      historical reports from our and other centres. Most deaths during follow-up
      occurred in patients who had been hospitalized. High rates of re-admission to the
      ED within 1 year are still an issue.

PMID- 25976906
TI  - Longevity of implantable cardioverter-defibrillators for cardiac
      resynchronization therapy in current clinical practice: an analysis according to
      influencing factors, device generation, and manufacturer.
AB  - AIMS: Device replacement at the time of battery depletion of implantable
      cardioverter-defibrillators (ICDs) may carry a considerable risk of complications
      and engenders costs for healthcare systems. Therefore, ICD device longevity is
      extremely important both from a clinical and economic standpoint. Cardiac
      resynchronization therapy defibrillators (CRT-D) battery longevity is shorter
      than ICDs. We determined the rate of replacements for battery depletion and we
      identified possible determinants of early depletion in a series of patients who
      had undergone implantation of CRT-D devices. METHODS AND RESULTS: We retrieved
      data on 1726 consecutive CRT-D systems implanted from January 2008 to March 2010
      in nine centres. Five years after a successful CRT-D implantation procedure, 46%
      of devices were replaced due to battery depletion. The time to device replacement
      for battery depletion differed considerably among currently available CRT-D
      systems from different manufacturers, with rates of batteries still in service at
      5 years ranging from 52 to 88% (log-rank test, P < 0.001). Left ventricular lead
      output and unipolar pacing configuration were independent determinants of early
      depletion [hazard ratio (HR): 1.96; 95% 95% confidence interval (CI): 1.57-2.46;
      P < 0.001 and HR: 1.58, 95% CI: 1.25-2.01; P < 0.001, respectively]. The
      implantation of a recent-generation device (HR: 0.57; 95% CI: 0.45-0.72; P <
      0.001), the battery chemistry and the CRT-D manufacturer (HR: 0.64; 95% CI: 0.47
      0.89; P = 0.008) were additional factors associated with replacement for battery
      depletion. CONCLUSION: The device longevity at 5 years was 54%. High left
      ventricular lead output and unipolar pacing configuration were associated with
      early battery depletion, while recent-generation CRT-Ds displayed better
      longevity. Significant differences emerged among currently available CRT-D
      systems from different manufacturers.

PMID- 25976907
TI  - First clinical evaluation of an atrial haemodynamic sensor lead for automatic
      optimization of cardiac resynchronization therapy.
AB  - AIMS: One option to improve cardiac resynchronization therapy (CRT) responder
      rates lies in the optimization of pacing intervals. A haemodynamic sensor
      embedded in the SonRtip atrial lead measures cardiac contractility and provides a
      systematic automatic atrioventricular and interventricular delays optimization.
      This multi-centre study evaluated the safety and performance of the lead, up to 1
      year. METHODS AND RESULTS: A total of 99 patients were implanted with the system
      composed of the lead and a CRT-Defibrillator device. Patients were followed at 1,
      3, 6, and 12 months post-implant. The primary safety objective was to demonstrate
      that the atrial lead complication free rate was superior to 90% at 3-months
      follow-up visit. A lead handling questionnaire was filled by implanting
      investigators. Lead electrical performances and the performance of the system to
      compute AV and VV delays were evaluated at each study visit over 1 year. The
      complication free rate at 3 months post-implant was 99.0% [95%CI 94.5-100.0%], P
      < 0.001. Electrical performances of the lead were adequate whatever the atrial
      lead position and remained stable over the study period. The optimization
      algorithm was able to compute AV and VV delays in 97% of patients, during >75% of
      the weeks. CONCLUSION: The atrial lead is safe to implant and shows stable
      electrical performance over time. It therefore offers a promising tool for
      automatic CRT optimization to further improve responder rates to CRT.

PMID- 25976908
TI  - Association between HbA1c levels with severity of coronary artery disease and
      short-term outcomes of acute ST-elevation myocardial infarction in nondiabetic
      patients.
AB  - BACKGROUND: The severity of coronary artery disease (CAD) is directly related to
      the quality of glucose control in diabetic patients. Additionally, mortality
      after an acute coronary syndrome is higher in patients with diabetes and it
      correlates to the level of glucose control. However, the role of higher
      gluconated hemoglobin in the process of coronary atherosclerosis and clinical
      outcome of acute myocardial infarction is unknown. OBJECTIVES: To evaluate the
      association of HbA1c level and severity of CAD and short-term outcomes of acute
      ST-elevation myocardial infarction (STEMI) in nondiabetics. METHODS: A total of
      290 nondiabetic patients with STEMI were prospectively enrolled following their
      admission. Patients were stratified into 2 groups based on the median percent of
      HbA1c (?5.8% 'Low' and >5.8% 'High'). The severity of CAD based on the Califf
      scoring system, in-hospital mortality and morbidities of STEMI were compared
      between groups. Patients were followed for 1 year after discharge to assess
      readmission and mortality rate. RESULTS: The severity score for CAD was
      significantly higher in the 'High' versus 'Low' HbA1c group (7.7 +/- 2.7 and 5.5
      +/- 2.6, p = 0.001). A total of 15 patients died in both groups during the follow
      up period. While in-hospital mortality was similar between the two groups, 12
      month mortality was significantly higher in the 'High' group (7.7% versus 2.7%, p
      = 0.043). In addition, the rehospitalization rate within 1 year was 8.8% in the
      'Low' group, which was significantly lower than 19.0% in the 'High' group (p =
      0.016). CONCLUSION: Among nondiabetic patients presenting with STEMI, the
      severity of CAD was higher in those with HbA1c level >5.8%; 1-year mortality and
      hospital readmission rates were also higher in this group of patients.

PMID- 25976909
TI  - Bottom Feeding and Beyond: How the Premaxillary Protrusion of Cypriniforms
      Allowed for a Novel Kind of Suction Feeding.
AB  - While much of the functional work on suction feeding has involved members of
      Acanthopterygii, an earlier cypriniform radiation led to over 3200 species
      filling nearly every freshwater trophic niche. Within the great majority of
      acanthomorph clades that have been investigated suction feeding and the
      underlying morphology responsible for the generation of rapid suction have been
      largely conserved. This conserved feeding-apparatus is often associated with
      increasing the force experienced by the prey item, thus making a strike on
      elusive prey more effective. Cypriniforms' trophic anatomy is comprised of a
      number of novelties used for benthic feeding, which characterized early members
      of this clade. The modified cypriniform structure of the oral jaws represents a
      situation in which a particular type of suction feeding allowed for probing the
      benthos with a more functionally maneuverable anatomy. Requisite evolutionary
      modifications included origin and elongation of a median kinethmoid, duplications
      of certain divisions of the muscles of the adductor mandibulae, and origin of a
      dorsal, intra-buccal muscular palatal organ used in winnowing detritus. The
      elongated kinethmoid (coupled with modified adductor muscles) allowed for a type
      of premaxillary protrusion that decoupled the upper and lower jaws, enabled
      premaxillary protrusions with a closed mouth, and facilitated benthic feeding by
      increasing functional flexibility. The resultant flow of fluid generated by
      cypriniforms is also quite flexible, with multiple instances of peak flow in a
      single feeding event. This greatly modified morphology allowed for a degree of
      kinematic maneuverability not seen within most acanthomorphs. Later cypriniform
      radiations into piscivorous, insectivorous, or planktivorous feeding guilds were
      associated with shortening of the kinethmoid and with simplified morphology of
      the adductor, likely involving an emphasis on ram feeding. Although this suite of
      morphological novelties seemingly originated within the context of benthic
      feeding, with minimal modifications these anatomical features were later coopted
      during radiations into different functional niches. 

PMID- 25976910
TI  - Evaluating microRNA profiles reveals discriminative responses following genotoxic
      or non-genotoxic carcinogen exposure in primary mouse hepatocytes.
AB  - Chemical carcinogenesis can be induced by genotoxic (GTX) or non-genotoxic (NGTX)
      carcinogens. GTX carcinogens have a well-described mode of action. However, the
      complex mechanisms by which NGTX carcinogens act are less clear and may result in
      conflicting results between species [e.g. Wy-14,643 (Wy)]. We hypothesise that
      common microRNA response pathways exist for each class of carcinogenic agents.
      Therefore, this study compares and integrates mRNA and microRNA expression
      profiles following short term acute exposure (24 and 48h) to three GTX [aflatoxin
      B1 (AFB1), benzo[a]pyrene (BaP) and cisplatin (CisPl)] or three NGTX (2,3,7,8
      tetrachloordibenzodioxine (TCDD), cyclosporine A (CsA) and Wy) carcinogens in
      primary mouse hepatocytes. Discriminative gene sets, microRNAs (not for 24h) and
      processes were identified following 24 and 48h of exposure. From the three
      discriminative microRNAs found following 48h of exposure, mmu-miR-503-5p revealed
      to have an interaction with mRNA target gene cyclin D2 (Ccnd2 - 12444) which was
      involved in the discriminative process of p53 signalling and metabolism.
      Following exposure to NGTX carcinogens Mmu-miR-503-5p may have an oncogenic
      function by stimulating Ccnd2 possibly leading to a tumourigenic cell cycle
      progression. By contrast, after GTX carcinogen exposure it may have a tumour
      suppressive function (repressing Ccnd2) leading to cell cycle arrest and to
      increased DNA repair activities. In addition, compound-specific microRNA-mRNA
      interactions [mmu-miR-301b-3p-Papss2 (for AFB1), as well as mmu-miR-29b-3p-Col4a2
      and mmu-miR-24-3p-Flna (for BaP)] were found to contribute to a better
      understanding of microRNAs in cell cycle arrest and the impairment of the DNA
      damage repair, an important hallmark of GTX-induced carcinogenesis. Overall, our
      results indicate that microRNAs represent yet another relevant intracellular
      regulatory level in chemical carcinogenesis. 

PMID- 25976911
TI  - The relationship between eating disorders and sexual trauma.
AB  - Research aimed at understanding the causes and comorbidities of eating disorders
      (ED) identifies sexual trauma as one potential pathway to the development and
      maintenance of eating disorders. Based on current literature, there are two main
      etiological pathways between sexual trauma and ED-body perceptions and
      psychological difficulties. However, previously published reviews on this topic
      are outdated and have not yielded consistent findings. Therefore, authors
      completed a literature review covering years 2004-2014 to examine the
      relationship between sexual trauma and ED according to both proposed pathway
      models. Authors utilized PubMed, GoogleScholar, and PsychINFO as search engines.
      Search terms included "sexual assault", "sexual abuse", "sexual trauma", and
      "rape" in conjunction with relevant ED terminology. Thirty-two studies met
      inclusion criteria for this review. Current data indicate an increased prevalence
      of sexual trauma for individuals with ED. Although limited, recent evidence
      suggests that sexual trauma precedes and contributes to the development of ED.
      Existing literature indicates that the body perceptions pathway may impact ED
      through body dissatisfaction, shame, sexual dysfunction, and fear of future
      sexual trauma. The psychological difficulties pathway indicates a link between ED
      and the desire to cope with the failure of the average expected environment,
      psychological diagnoses, the need for control, and the regulation of emotions.
      However, further research is needed to assess the potential causal role that
      sexual trauma may play in the etiology of ED. 

PMID- 25976912
TI  - Management of dose variability and side effects for individualized cancer
      pharmacotherapy with tyrosine kinase inhibitors.
AB  - Molecular-targeted therapies with tyrosine kinase inhibitors (TKIs) have provided
      a major breakthrough in cancer treatment. These agents are given orally and
      demonstrated to be substrates for drug transporters. In clinical settings, TKIs
      are mainly used at a fixed dose, but wide interpatient variability has been
      observed in their pharmacokinetics and/or pharmacodynamics. Genetic polymorphisms
      of ABC transporters, drug-drug interaction and adherence are among the factors
      causing such variation. To overcome these problems, therapeutic drug monitoring
      has been applied in clinical practice for patient care. Skin disorders are
      frequently observed as adverse drug reactions when using TKIs, and are commonly
      managed by symptomatic therapy based on clinical experience. Recent studies have
      provided some insights into the molecular mechanisms underlying skin disorders
      induced by TKIs. This review article summarizes the accumulated clinical and
      basic pharmacological evidence of TKIs, focusing on erlotinib, sorafenib and
      sunitinib. 

PMID- 25976914
TI  - Withdrawal of treatment from "dying" teenager to be reconsidered by court after
      he defies expectations.

PMID- 25976913
TI  - Prediction of healing progress of pressure ulcers by distribution analysis of
      protein markers on necrotic tissue: A retrospective cohort study.
AB  - Predicting the short-term healing progress of pressure ulcers is important for
      providing timely and appropriate intervention. Although there are some prediction
      methods available, these are unsuitable for ulcers with abundant necrotic tissue.
      We aimed to elucidate the relationship between necrotic tissue alteration and
      protein distributions on ulcers to establish a new prediction method. Thirty
      eight pressure ulcers were retrospectively analyzed. Protein distributions on
      necrotic tissue were evaluated by the wound blotting at three levels: marker
      protein positivity, signal patterns (speckled, heterogeneous, or homogeneous),
      and the occupation of heterogeneous pattern. Peroxidase, alkaline phosphatase,
      tumor necrosis factor alpha, and matrix metalloproteinase-2 were used as marker
      proteins. One-week necrotic tissue alteration was classified as liquefaction or
      nonliquefaction, and associations with protein distributions were analyzed. The
      peroxidase positivity was significantly higher in the liquefaction than in the
      nonliquefaction (p = 0.031). In peroxidase-positive samples, the proportion of
      nonliquefaction samples was significantly higher in the heterogeneous pattern (p
      = 0.029). In the heterogeneous-patterned samples, the proportion of samples with
      an occupation values greater than the median value tended to be higher in the
      nonliquefaction (p = 0.087). There was no significant relationship between
      liquefaction and other markers. Peroxidase positivity predicts 1-week
      liquefaction of necrotic tissue, while a heterogeneous pattern indicates
      nonliquefaction. 

PMID- 25976915
TI  - The biocathode of microbial electrochemical systems and microbially-influenced
      corrosion.
AB  - The cathode reaction is one of the most important limiting factors in
      bioelectrochemical systems even with precious metal catalysts. Since aerobic
      bacteria have a much higher affinity for oxygen than any known abiotic cathode
      catalysts, the performance of a microbial fuel cell can be improved through the
      use of electrochemically-active oxygen-reducing bacteria acting as the cathode
      catalyst. These consume electrons available from the electrode to reduce the
      electron acceptors present, probably conserving energy for growth. Anaerobic
      bacteria reduce protons to hydrogen in microbial electrolysis cells (MECs). These
      aerobic and anaerobic bacterial activities resemble those catalyzing microbially
      influenced corrosion (MIC). Sulfate-reducing bacteria and homoacetogens have been
      identified in MEC biocathodes. For sustainable operation, microbes in a
      biocathode should conserve energy during such electron-consuming reactions
      probably by similar mechanisms as those occurring in MIC. A novel hypothesis is
      proposed here which explains how energy can be conserved by microbes in MEC
      biocathodes. 

PMID- 25976916
TI  - Hydrothermal acid treatment for sugar extraction from Golenkinia sp.
AB  - In this study, hydrothermal acid treatment for efficient recovery of sugar from
      Golenkinia sp. was investigated. The initial glucose and XMG (xylose, mannose,
      and galactose) contents of a prepared Golenkinia sp. solution (40g/L) were 15.05
      and 5.24g/L, respectively. The microalgal cell walls were hydrolyzed, for sugar
      recovery, by enzymatic saccharification and/or hydrothermal acid treatment. Among
      the various hydrothermal acid treatment conditions, the most optimal were the
      2.0% H2SO4 concentration at 150 degrees C for 15min, under which the glucose- and
      XMG-extraction yields were 71.7% and 64.9%, respectively. By pH 4.8, 50 degrees C
      enzymatic hydrolysis after optimal hydrothermal acid treatment, the glucose- and
      XMG-extraction yields were additionally increased by 8.3% and 0.8%, respectively.
      After hydrothermal acid treatment, the combination with the enzymatic hydrolysis
      process improved the total sugar yield of Golenkinia sp. to 75.4%. 

PMID- 25976917
TI  - Characterization and expression analysis of a gene encoding CBF/DREB1
      transcription factor from mangrove Aegiceras corniculatum.
AB  - Several transcription factors play important roles in survival of plants under
      cold, drought and salt stresses by serving as master regulator of sets of
      downstream stress-responsive genes. A gene encoding CBF/DREB1 transcription
      factor (C-repeat binding factor/dehydration responsive element-binding factor 1)
      was isolated from mangrove Aegiceras corniculatum and designated AcCBF1. The full
      length cDNA of AcCBF1 was 896 bp containing 618 bp ORF encoding a protein of 205
      amino acids. Multiple sequence analysis showed that the corresponding protein had
      100 % identity to AmCBF1 (KC776908) from mangrove Avicennia marina, and contains
      an AP2/ERE DNA-binding domain and two CBF signature sequences. Expression
      analyses based on quantitative real-time PCR revealed that the AcCBF1 gene was
      expressed in all tissues of A. corniculatum under normal condition with the
      highest expression level detected in leaves. When exposed to abiotic stresses,
      AcCBF1 gene showed different expression patterns in different tissues. Generally,
      AcCBF1 gene could be rapidly and strongly induced by cold and drought, while
      slightly induced by abscisic acid and salinity. Furthermore, light could
      positively regulate the cold-induction level of AcCBF1. These results suggest
      that the AcCBF1 may be playing important role in the signaling pathway of cold
      stress and also involved in the cross-talk among abiotic stresses. Further
      studies focusing on the promotors and downstream stress-responsive genes of
      AcCBF1 will help to better understand the regulatory mechanisms of mangrove A.
      corniculatum under abiotic stresses.

PMID- 25976918
TI  - Ecological risk assessment for mink and short-tailed shrew exposed to PCBs,
      dioxins, and furans in the Housatonic River area.
AB  - A probabilistic risk assessment was conducted to characterize risks to a
      representative piscivorous mammal (mink, Mustela vison) and a representative
      carnivorous mammal (short-tailed shrew, Blarina brevicauda) exposed to PCBs,
      dioxins, and furans in the Housatonic River area downstream of the General
      Electric (GE) facility in Pittsfield, Massachusetts. Contaminant exposure was
      estimated using a probabilistic total daily intake model and parameterized using
      life history information of each species and concentrations of PCBs, dioxins, and
      furans in prey collected in the Housatonic River study area. The effects
      assessment preferentially relied on dose-response curves but defaulted to
      benchmarks or other estimates of effect when there were insufficient toxicity
      data. The risk characterization used a weight of evidence approach. Up to 3 lines
      of evidence were used to estimate risks to the selected mammal species: 1)
      probabilistic exposure and effects modeling, 2) field surveys, and 3) species
      specific feeding or field studies. The weight of evidence assessment indicated a
      high risk for mink and an intermediate risk for short-tailed shrew.

PMID- 25976919
TI  - Prospective, Multicenter Evaluation of Allogeneic Bone Matrix Containing Viable
      Osteogenic Cells in Foot and/or Ankle Arthrodesis.
AB  - BACKGROUND: Cellular bone allograft (CBA) possesses osteogenic, osteoinductive,
      and osteoconductive elements essential for bone healing. The purpose of this
      study was to assess the safety and effectiveness of CBA in foot and/or ankle
      arthrodeses. METHODS: A prospective, multicenter, open-label clinical trial using
      CBA was performed. At 6 weeks and at 3, 6, and 12 months, imaging was performed
      and the subject's pain, function, and quality of life (QOL) status (Visual Analog
      Scale, American Orthopaedic Foot & Ankle Society Hindfoot Scale, and the Short
      Form 36) were recorded. The per protocol population consisted of 92 patients at 6
      months and 76 patients at 12 months, with 153 and 129 total arthrodeses,
      respectively. RESULTS: At 6 months, fusion rates were 68.5% for all patients and
      81.1% for all joints; at 12 months, rates were 71.1% and 86.8%, respectively.
      Certain high-risk subjects (eg, with diabetes or obesity) had fusion rates
      comparable to those of normal patients. Statistically significant improvements in
      pain, function, and QOL were observed, and fusion correlated with both function
      and QOL outcomes at 6 and 12 months. There were no adverse events attributable to
      CBA. CONCLUSION: Fusion rates using CBA were higher than or comparable to fusion
      rates with autograft that have been reported in the recent literature, and CBA
      fusion rates were not adversely affected by several high-risk patient factors.
      CBA was a safe and effective graft material to achieve fusion in patients with
      compromised bone healing and may provide an effective autograft replacement for
      foot and/or ankle arthrodeses. LEVEL OF EVIDENCE: Level II, prospective study.

PMID- 25976921
TI  - Identification and genome characterization of genotype B and genotype C bovine
      parainfluenza type 3 viruses isolated in the United States.
AB  - BACKGROUND: Bovine parainfluenza 3 viruses (BPI3V) are respiratory pathogens of
      cattle that cause disease singly but are often associated with bovine respiratory
      disease complex (BRDC) in conjunction with other viral and bacterial agents.
      Bovine vaccines currently contain BPI3V to provide protection against the virus,
      but there is no current information regarding the BPI3V strains that are
      circulating in the U.S. RESULTS: A project was initiated to sequence archival
      BPI3V isolates to study viral evolution over time. This was done with a deep
      sequencing protocol that generated sequences of multiple RNA virus genomes
      simultaneously. Analysis of the BPI3V sequences revealed that, in addition to the
      genotype A (BPI3Va) viruses previously described in the United States, there were
      two additional genotypes of BPI3V circulating that had been described only in
      Australia (BPI3Vb) and Asia (BPI3Vc). The U.S. BPI3Vb and BPI3Vc isolates showed
      some divergence from the Australian and Asian strains; the BPI3Vb were 93 %
      similar to the Australian Q5592 strain and the BPI3Vc viruses were 98 % similar
      to the 12Q061 strain that was described in South Korea. Overall, the three
      genotypes were 82 to 84 % identical to each other and 80 % identical to the most
      similar human PI3V. Cross-neutralization studies using an APHIS/NVSL BPI3V
      reference serum showed that neutralization titers against the genotype B and C
      viruses were 4- to >=16-fold less then the titer against the APHIS BPI3Va
      reference strain, SF-4. CONCLUSIONS: This study clearly demonstrated that BPI3Vb
      and BPI3Vc strains, previously thought to be foreign to the U.S., are indeed
      circulating in domestic livestock herds. Based on virus neutralization using
      polyclonal antisera, there were antigenic differences between viruses from these
      genotypes and the BPI3Va viruses that are included in currently marketed bovine
      vaccines. Further study of these viruses is warranted to determine pathogenic
      potential and cross-protection afforded by vaccination.

PMID- 25976920
TI  - Fractal analysis of nuclear histology integrates tumor and stromal features into
      a single prognostic factor of the oral cancer microenvironment.
AB  - BACKGROUND: The lack of prognostic biomarkers in oral squamous cell carcinoma
      (OSCC) has hampered treatment decision making and survival in OSCC remains poor.
      Histopathological features are used for prognostication in OSCC and, although
      useful for predicting risk, manual assessment of histopathology is subjective and
      labour intensive. In this study, we propose a method that integrates multiple
      histopathological features of the tumor microenvironment into a single, digital
      pathology-based biomarker using nuclear fractal dimension (nFD) analysis.
      METHODS: One hundred and seven consecutive OSCC patients diagnosed between 1998
      and 2006 in Calgary, Canada were included in the study. nFD scores were generated
      from DAPI-stained images of tissue microarray (TMA) cores. Ki67 protein
      expression was measured in the tumor using fluorescence immunohistochemistry
      (IHC) and automated quantitative analysis (AQUA(r)). Lymphocytic infiltration
      (LI) was measured in the stroma from haematoxylin-eosin (H&E)-stained TMA slides
      by a pathologist. RESULTS: Twenty-five (23.4%) and 82 (76.6%) patients were
      classified as high and low nFD, respectively. nFD was significantly associated
      with pathological tumor-stage (pT-stage; P = 0.01) and radiation treatment (RT; P
      = 0.01). High nFD of the total tumor microenvironment (stroma plus tumor) was
      significantly associated with improved disease-specific survival (DSS; P =
      0.002). No association with DSS was observed when nFD of either the tumor or the
      stroma was measured separately. pT-stage (P = 0.01), pathological node status (pN
      status; P = 0.02) and RT (P = 0.03) were also significantly associated with DSS.
      In multivariate analysis, nFD remained significantly associated with DSS [HR 0.12
      (95% CI 0.02-0.89, P = 0.04)] in a model adjusted for pT-stage, pN-status and RT.
      We also found that high nFD was significantly associated with high tumor
      proliferation (P < 0.0001) and high LI (P < 0.0001), factors that we and others
      have shown to be associated with improved survival in OSCC. CONCLUSIONS: We
      provide evidence that nFD analysis integrates known prognostic factors from the
      tumor microenvironment, such as proliferation and immune infiltration, into a
      single digital pathology-based biomarker. Prospective validation of our results
      could establish nFD as a valuable tool for clinical decision making in OSCC.

PMID- 25976922
TI  - Factors influencing engagement with case managers: Perspectives of young people
      with a diagnosis of first episode psychosis.
AB  - Holistic treatment during a first episode psychosis (FEP) can significantly
      impact the longevity and chronicity of the illness, as well as reduce the risk of
      premature death by suicide. However, treatment can only be effective if the young
      person participates. Given that 19-40% of young people disengage from early
      intervention services for FEP, this qualitative study aimed to understand how
      young people experienced engagement with case managers at an early intervention
      service. Semistructured interviews were conducted with seven young people and
      themes were identified using interpretive phenomenological analysis. Young people
      detailed how engagement with a service could be viewed as a process, following
      different stages between initial referral and discharge. Throughout this process,
      a number of factors influenced young people's decision to engage with, or
      disengage from, their case manager. This created a push-pull dynamic with periods
      of good engagement and poor engagement. Discussion of this dynamic adds nuance to
      established scholarship about engagement, including shifts over time in the
      importance of client empowerment and valued features of therapeutic
      relationships. Awareness and understanding of these concepts may guide changes to
      early intervention services and address the core issue of engagement. 

PMID- 25976923
TI  - Disentangling neural processes of egocentric and allocentric mental spatial
      transformations using whole-body photos of self and other.
AB  - Mental imagery of one's body moving through space is important for imagining
      changing visuospatial perspectives, as well as for determining how we might
      appear to other people. Previous neuroimaging research has implicated the
      temporoparietal junction (TPJ) in this process. It is unclear, however, how
      neural activity in the TPJ relates to the rotation perspectives from which mental
      spatial transformation (MST) of one's own body can take place, i.e. from an
      egocentric or an allocentric perspective. It is also unclear whether TPJ
      involvement in MST is self-specific or whether the TPJ may also be involved in
      MST of other human bodies. The aim of the current study was to disentangle neural
      processes involved in egocentric versus allocentric MSTs of human bodies
      representing self and other. We measured functional brain activity of healthy
      participants while they performed egocentric and allocentric MSTs in relation to
      whole-body photographs of themselves and a same-sex stranger. Findings indicated
      higher blood oxygen level-dependent (BOLD) response in bilateral TPJ during
      egocentric versus allocentric MST. Moreover, BOLD response in the TPJ during
      egocentric MST correlated positively with self-report scores indicating how
      awkward participants felt while viewing whole-body photos of themselves. These
      findings considerably advance our understanding of TPJ involvement in MST and its
      interplay with self-awareness. 

PMID- 25976924
TI  - Investigating the dynamics of the brain response to music: A central role of the
      ventral striatum/nucleus accumbens.
AB  - Ventral striatal activity has been previously shown to correspond well to reward
      value mediated by music. Here, we investigate the dynamic brain response to music
      and manipulated counterparts using functional magnetic resonance imaging (fMRI).
      Counterparts of musical excerpts were produced by either manipulating the
      consonance/dissonance of the musical fragments or playing them backwards (or
      both). Results show a greater involvement of the ventral striatum/nucleus
      accumbens both when contrasting listening to music that is perceived as pleasant
      and listening to a manipulated version perceived as unpleasant (backward
      dissonant), as well as in a parametric analysis for increasing pleasantness.
      Notably, both analyses yielded a ventral striatal response that was strongest
      during an early phase of stimulus presentation. A hippocampal response to the
      musical stimuli was also observed, and was largely mediated by processing
      differences between listening to forward and backward music. This hippocampal
      involvement was again strongest during the early response to the music. Auditory
      cortex activity was more strongly evoked by the original (pleasant) music
      compared to its manipulated counterparts, but did not display a similar decline
      of activation over time as subcortical activity. These findings rather suggest
      that the ventral striatal/nucleus accumbens response during music listening is
      strongest in the first seconds and then declines. 

PMID- 25976925
TI  - Decoding speech perception from single cell activity in humans.
AB  - Deciphering the content of continuous speech is a challenging task performed
      daily by the human brain. Here, we tested whether activity of single cells in
      auditory cortex could be used to support such a task. We recorded neural activity
      from auditory cortex of two neurosurgical patients while presented with a short
      video segment containing speech. Population spiking activity (~20 cells per
      patient) allowed detection of word onset and decoding the identity of perceived
      words with significantly high accuracy levels. Oscillation phase of local field
      potentials (8-12Hz) also allowed decoding word identity although with lower
      accuracy levels. Our results provide evidence that the spiking activity of a
      relatively small population of cells in human primary auditory cortex contains
      significant information for classification of words in ongoing speech. Given
      previous evidence for overlapping neural representation during speech perception
      and production, this may have implications for developing brain-machine
      interfaces for patients with deficits in speech production. 

PMID- 25976928
TI  - Eosinophilic ileocolitis due to Enterobius vermicularis infection: a rare cause
      of anemia.

PMID- 25976926
TI  - fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex.
AB  - INTRODUCTION: Paired associative stimulation (PAS), is a novel non-invasive
      technique where two neural substrates are employed in a temporally coordinated
      manner in order to modulate cortico-motor excitability within the motor cortex
      (M1). In swallowing, combined pharyngeal electrical and transcranial-magnetic
      stimulation induced beneficial neurophysiological and behavioural effects in
      healthy subjects and dysphagic stroke patients. Here, we aimed to investigate the
      whole-brain changes in neural activation during swallowing using functional
      magnetic resonance imaging (fMRI) following PAS application and in parallel
      assess associated GABA changes with magnetic resonance spectroscopy (MRS).
      METHODS: Healthy adults (n=11, 38+/-9years old) were randomised to receive real
      and sham PAS to the 'stronger' motor cortex pharyngeal representation, on 2
      separate visits. Following PAS, event-related fMRI was performed to assess
      changes in brain activation in response to water and saliva swallowing and during
      rest. Data were analysed (SPM8) at P<.001. MRS data were acquired using MEGA
      PRESS before and after the fMRI acquisitions on both visits and GABA
      concentrations were measured (AMARES, jMRUI). RESULTS: Following real PAS, BOLD
      signal changes (group analyses) increased at the site of stimulation during water
      and saliva swallowing, compared to sham PAS. It is also evident that PAS induced
      significant increases in BOLD signal to contralateral (to stimulation)
      hemispheric areas that are of importance to the swallowing neural network.
      Following real PAS, GABA:creatine ratio showed a trend to increase contralateral
      to PAS. CONCLUSION: Targeted PAS applied to the human pharyngeal motor cortex
      induces local and remote changes in both primary and non-primary areas for water
      and saliva tasks. There is a possibility that changes of the inhibitory
      neurotransmitter, GABA, may play a role in the changes in BOLD signal. These
      findings provide evidence for the mechanisms underlying the beneficial effects of
      PAS on the brain swallowing network.

PMID- 25976927
TI  - Parkinson's disease biomarkers program brain imaging repository.
AB  - The Parkinson's Disease Biomarkers Program (PDBP) is a multi-site study designed
      to identify Parkinson's disease (PD) biomarkers that can be used to improve the
      understanding of PD pathophysiology and to develop tools that provide novel
      measures to evaluate PD clinical trials. The PDBP consortium comprises numerous
      individual projects of which two are specifically geared to the development of
      brain imaging markers for diagnosis, progression, and prognosis of PD or related
      disorders. All study data from PD patients, atypical Parkinsonian patients,
      patients with essential tremor, and healthy controls collected from the sites are
      integrated in the PDBP database and will be publically available. All subjects
      are asked to submit blood samples, and undergo a battery of clinical evaluations
      that cover motor, cognitive, and other background information. In addition, a
      subset of subjects contributed cerebrospinal fluid samples. A restricted access,
      web-based Data Management Resource facilitates rapid sharing of data and
      biosamples across the entire PD research community. The PDBP consortium is a
      useful resource for research and collaboration aimed at the discovery of
      biomarkers and their use in understanding the pathophysiology of PD. 

PMID- 25976929
TI  - Locally advanced anal canal carcinoma: is the addition of cetuximab the answer?

PMID- 25976930
TI  - Psychological stress in patients with anal fistula.
AB  - AIM: Psychological stress is known to affect the immunologic system and the
      inflammatory response. The aim of this study was to assess the presence of
      psychological stress, anxiety, and depression in patients with anal fistula.
      METHODS: Consecutive patients with anal fistula, hemorrhoids, and normal
      volunteers were studied prospectively. Stressful life events were recorded and
      subjects were asked to complete the state-trait anxiety inventory (STAI), a
      depression scale, and three different reactive graphic tests (RGT). RESULTS:
      Seventy-eight fistula patients, 73 patients with grade III-IV hemorrhoids, and 37
      normal volunteers were enrolled. Of the fistula patients, 65 (83 %) reported one
      or more stressful events in the year prior to diagnosis, compared to 16 (22 %) of
      the hemorrhoid patients (P = 0.001). There were no significant differences in the
      percentage of subjects with abnormal trait anxiety (i.e., proneness for anxiety)
      and depression scores between fistula patients, hemorrhoid patients, and
      controls. Fistula patients had significantly higher (i.e., better) scores
      compared to hemorrhoid patients in two of three RGT and significantly lower
      (i.e., worse) scores in all three RGT compared to healthy volunteers. Of 37
      patients followed up for a median of 28 months (range 19-41 months) after
      surgery, 8 (21.6 %) had persistent or recurrent sepsis. There was no significant
      difference in depression, STAI, and RGT scores between patients with sepsis and
      patients whose fistula healed. CONCLUSION: Our results suggest that an altered
      emotional state plays an important role in the pathogenesis of anal fistula and
      underline the importance of psychological screening in patients with anorectal
      disorders.

PMID- 25976931
TI  - Seasonal variation in onset and relapse of IBD and a model to predict the
      frequency of onset, relapse, and severity of IBD based on artificial neural
      network.
AB  - BACKGROUND: Previous research has yielded conflicting data as to whether the
      natural history of inflammatory bowel disease follows a seasonal pattern. The
      purpose of this study was (1) to determine whether the frequency of onset and
      relapse of inflammatory bowel disease follows a seasonal pattern and (2) to
      establish a model to predict the frequency of onset, relapse, and severity of
      inflammatory bowel disease (IBD) with meteorological data based on artificial
      neural network (ANN). METHOD: Patients with diagnosis of ulcerative colitis (UC)
      or Crohn's disease (CD) between 2003 and 2011 were investigated according to the
      occurrence of onset and flares of symptoms. The expected onset or relapse was
      calculated on a monthly basis over the study period. For artificial neural
      network (ANN), patients from 2003 to 2010 were assigned as training cohort and
      patients in 2011 were assigned as validation cohort. Mean square error (MSE) and
      mean absolute percentage error (MAPE) were used to evaluate the predictive
      accuracy. RESULTS: We found no seasonal pattern of onset (P = 0.248) and relapse
      (P = 0.394) among UC patients. But, the onset (P = 0.015) and relapse (P = 0.004)
      of CD were associated with seasonal pattern, with a peak in July and August. ANN
      had average accuracy to predict the frequency of onset (MSE = 0.076, MAPE =
      37.58%) and severity of IBD (MSE = 0.065, MAPE = 42.15%) but high accuracy in
      predicting the frequency of relapse of IBD (MSE = 0.009, MAPE = 17.1%).
      CONCLUSION: The frequency of onset and relapse in IBD showed seasonality only in
      CD, with a peak in July and August, but not in UC. ANN may have its value in
      predicting the frequency of relapse among patients with IBD.

PMID- 25976932
TI  - Small heterodimer partner attenuates profibrogenic features of hepatitis C virus
      infected cells.
AB  - BACKGROUND & AIMS: An atypical orphan nuclear receptor small heterodimer partner
      (SHP) is known to be regulated by AMP-activated protein kinase (AMPK). Both of
      them inhibit TGF-beta and Smad signalling and exhibit antifibrotic activity in
      the liver. However, little is known about the protective effects of SHP and AMPK
      against hepatitis c virus (HCV)-induced hepatic fibrosis. METHODS: Levels of SHP,
      p-AMPK and fibrotic markers in HCV-infected human liver and in Huh-7.5 cells
      infected with HCV genotype 2a (JFH-1) were investigated. The effect of adenovirus
      mediated overexpression of SHP (Ad-SHP) and AMPK activation via metformin and 5
      amino-1-b-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) on fibrotic gene
      expression was evaluated in HCV-infected cells. Finally, we examined the effect
      of Ad-SHP and AMPK activators on invasion and activation of LX2 human HSCs
      induced by conditioned media from HCV-infected hepatocyte (CM). RESULTS: In HCV
      infected human livers and Huh-7.5 cells infected with HCV, SHP mRNA and protein
      levels were diminished compared with controls, whereas profibrotic factors were
      increased. Pharmacological AMPK activation recovered SHP expression, and Ad-SHP
      inhibited HCV-induced fibrotic gene expression. This finding was accompanied by
      inhibition of HCV-stimulated nuclear factor-kappa B, an inducer of TGF-beta.
      Moreover, CytoSelect invasion assay revealed that enhanced activity and
      invasiveness of hepatic stellate cells induced by CM. CONCLUSION: These results
      demonstrate that overexpression of SHP and activation of AMPK reverses
      profibrogenic features of HCV-infected cells by decreasing TGF-beta and fibrotic
      gene expression. These findings provide a rationale for SHP as a possible
      therapeutic target against HCV-induced hepatic fibrosis.

PMID- 25976934
TI  - The Circadian Gene Clock Plays an Important Role in Cell Apoptosis and the DNA
      Damage Response In Vitro.
AB  - The Clock gene, an indispensable component of the circadian clock, not only
      modulates circadian oscillations but also regulates organismal function. We
      examined whether silencing the expression of the human Clock gene in glioma cells
      influences cell growth and induces apoptosis after irradiation. Silencing the
      expression of Clock in a human glioma cell line (U87MG), but not in a control
      glioma cell line, resulted in increased apoptosis and cell cycle arrest.
      Moreover, silencing Clock expression altered the expression of apoptosis-related
      genes. The protein levels of c-Myc and Cyclin B1 were downregulated, but those of
      p53 were upregulated, in human Clock-silenced U87MG cells compared with control
      cells. Our results suggest that the circadian gene human Clock may play an
      important role in carcinogenesis by inhibiting apoptotic cell death via
      attenuating proapoptotic signaling.

PMID- 25976933
TI  - HIV infection and antiretroviral therapy lead to unfolded protein response
      activation.
AB  - BACKGROUND: The unfolded protein response (UPR) is one of the pathways triggered
      to ensure quality control of the proteins assembled in the endoplasmic reticulum
      (ER) when cell homeostasis is compromised. This mechanism is primarily composed
      of three transmembrane proteins serving as stress sensors: PKR-like ER kinase
      (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1
      (IRE1). These three proteins' synergic action elicits translation and
      transcriptional downstream pathways, leading to less protein production and
      activating genes that encode important proteins in folding processes, including
      chaperones. Previous reports showed that viruses have evolved mechanisms to
      curtail or customize this UPR signaling for their own benefit. However, HIV
      infection's effect on the UPR has scarcely been investigated. METHODS: This work
      investigated UPR modulation by HIV infection by assessing UPR-related protein
      expression under in vitro and in vivo conditions via Western blotting.
      Antiretroviral (ARV) drugs' influence on this stress response was also
      considered. RESULTS: In in vitro and in vivo analyses, our results confirm that
      HIV infection activates stress-response components and that ARV therapy
      contributes to changes in the UPR's activation profile. CONCLUSIONS: This is the
      first report showing UPR-related protein expression in HIV target cells derived
      directly from HIV-infected patients receiving different ARV therapies. Thus, two
      mechanisms may occur simultaneously: interference by HIV itself and the ARV
      drugs' pharmacological effects as UPR activators. New evidence of how HIV
      modulates the UPR to enhance its own replication and secure infection success is
      also presented.

PMID- 25976936
TI  - Conductivity of Nanowire Arrays under Random and Ordered Orientation
      Configurations.
AB  - A computational model was developed to analyze electrical conductivity of random
      metal nanowire networks. It was demonstrated for the first time through use of
      this model that a performance gain in random metal nanowire networks can be
      achieved by slightly restricting nanowire orientation. It was furthermore shown
      that heavily ordered configurations do not outperform configurations with some
      degree of randomness; randomness in the case of metal nanowire orientations acts
      to increase conductivity. 

PMID- 25976935
TI  - Mental Health and Substance Use Factors Associated With Unwanted Sexual Contact
      Among U.S. Active Duty Service Women.
AB  - Many U.S. military women are exposed to unwanted sexual contact during military
      service, which can have important implications for mental health. Using data from
      the 2008 Department of Defense Survey of Health Related Behaviors, we employed
      multiple logistic regression methods to examine whether unwanted sexual contact
      was associated with stress, screening positive for mental disorders, or substance
      use, among active duty service women. The sample included 7,415 female military
      personnel, of whom 13.4% reported unwanted sexual contact (including any touching
      of genitals) since entering the military. After adjusting for potentially
      confounding variables, factors independently associated with unwanted sexual
      contact included military-related stress (adjusted odds ratio [AOR] = 2.44),
      family/personal life-related stress (AOR = 1.78), and gender-related stress (AOR
      = 1.98) in the past 12 months. In addition, screening positive for depression,
      anxiety, posttraumatic stress disorder, or psychological distress, and suicidal
      ideation or attempt were associated with unwanted sexual contact (AOR = 1.57
      2.11). For drug/alcohol use, only misuse of tranquilizers/muscle relaxers (past
      12 months) was associated with report of unwanted sexual contact (AOR = 1.35).
      Given the prevalence of unwanted sexual contact and corresponding adverse health
      outcomes in this sample of active duty women, strategies to create military
      structural/cultural changes and reduce gender-related stress and sexism are
      needed. 

PMID- 25976937
TI  - Review of the advances in treatment for Alzheimer disease: Strategies for
      combating beta-amyloid protein.
AB  - INTRODUCTION: Alzheimer disease (AD) is a major neurodegenerative disorder which
      eventually results in total intellectual disability. The high global prevalence
      and the socioeconomic burden associated with the disease pose major challenges
      for public health in the 21st century. In this review we focus on both existing
      treatments and the therapies being developed, which principally target the beta
      amyloid protein. DISCUSSION: The amyloidogenic hypothesis proposes that beta
      amyloid plays a key role in AD. Several pharmacological approaches aim to reduce
      the formation of beta-amyloid peptides by inhibiting the beta-secretase and gamma
      secretase enzymes. In addition, both passive and active immunotherapies have been
      developed for the purpose of inhibiting beta-amyloid peptide aggregation.
      CONCLUSIONS: Progress in identifying the molecular basis of AD may provide better
      models for understanding the causes of this neurodegenerative disease. The lack
      of efficacy of solanezumab (a humanised monoclonal antibody that promotes beta
      amyloid clearance in the brain), demonstrated by 2 recent Phase III clinical
      trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs
      to be revised.

PMID- 25976938
TI  - HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT
      abnormalities in a series of 5 new cases.
AB  - INTRODUCTION: Transient headache and neurological deficits with cerebrospinal
      fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes
      accompanied by neurological deficits consisting of motor, sensory, or aphasic
      symptoms. Electroencephalogram (EEG) and single photon emission computed
      tomography (SPECT) may show focal abnormalities that correspond to the
      neurological deficits. We aim to evaluate the correlation between focal deficit
      topography and EEG or SPECT abnormalities in 5 new cases. PATIENTS: We
      retrospectively reviewed patients attended in a tertiary hospital (January 2010
      May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 +/-
      7.7 (21-39) years. They presented 3.4 +/- 2.6 episodes of headache (range, 2-8)
      of moderate to severe intensity and transient neurological deficits over a
      maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312
      cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological
      studies. RESULTS: At least one EEG was performed in 4 patients and SPECT in 3
      patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1
      brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal
      SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed
      decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG
      with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right
      parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2
      episodes, right hemisphere and left hemisphere, EEG with right temporal slowing;
      normal SPECT. CONCLUSION: The neurological deficits accompanying headache in
      HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of
      all EEG abnormalities were not uncommon in our series and they did not always
      correlate to the topography of focal deficits.

PMID- 25976939
TI  - Focal leptomeningeal uptake, a new radiological finding in pseudomigraine with
      pleocytosis.

PMID- 25976940
TI  - Anosognosia in Alzheimer disease: Prevalence, associated factors, and influence
      on disease progression.
AB  - INTRODUCTION: Anosognosia is a frequent symptom in Alzheimer disease (AD). The
      objective of this article is to describe prevalence of this condition at time of
      diagnosis and analyse any predisposing factors and their influence on disease
      progression. METHODS: Observational, prospective, and analytical multi-centre
      study in an outpatient setting. Patients recently diagnosed with AD (NINCDS-ADRDA
      criteria) were included. Each patient underwent two cognitive, functional, and
      neuropsychiatric assessments separated by an interval of 18 months. The Clinical
      Insight Rating Scale was employed as a measure of anosognosia (CIR, scored 0-8).
      Progression was defined as an increase in the Clinical Dementia Rating Scale-sum
      of boxes of more than 2.5 points. The predictor variables were analysed using
      binary logistic regression. RESULTS: The study included 127 patients, and 94
      completed both assessments. Of the total, 31.5% displayed severe anosognosia (CIR
      7-8); 39.4%, altered level of consciousness (CIR 3-6); and 29.1%, normal
      awareness (CIR 0-2). The median baseline CIR in this cohort was 4 (Q1-Q3: 1-7),
      and at 18 months, 6 (Q1-Q3: 3-8), P<.001. Advanced age (odds ratio (OR) 2.43; CI
      95%:1.14-5.19), lower educational level (OR 2.15; CI 95%:1.01-4.58), and more
      marked neuropsychiatric symptoms (OR 2.66; CI 95%:1.23-5.74) were predictor
      variables of anosognosia. Baseline CIR was similar in the groups with and without
      significant clinical progression. CONCLUSIONS: The large majority of patients
      with AD at the time of diagnosis showed significant anosognosia, and this
      condition was associated with advanced age, lower educational level, and more
      marked behavioural symptoms. Our results did not show that anosognosia had an
      effect on the initial clinical progression of AD after diagnosis.

PMID- 25976941
TI  - Neurotrophic keratitis secondary to cerebral malformation.

PMID- 25976942
TI  - [Cost-effectiveness analysis of interferon beta-1b as treatment for patients with
      clinically isolated syndrome suggestive of multiple sclerosis in Spain].
AB  - INTRODUCTION: The BENEFIT study has demonstrated the benefits of early treatment
      with interferon beta 1b (IFNbeta-1b). The objective of this study was to estimate
      the efficiency of early vs delayed IFNbeta-1b treatment in patients with
      clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in
      Spain. METHODS: A Markov model reflecting the social perspective was developed
      with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients
      with CIS, whose health status had been measured on the Expanded Disability
      Symptom Scale (EDSS), included patients who received early IFNbeta-1b treatment
      and those who did not. Data from the BENEFIT study were used to model EDSS
      progression and transitions to MS. Costs were estimated from published
      literature. Patient utilities were derived from EQ-5D data and published data.
      Mortality was estimated using life tables and EDSS data. Costs (? at 2013 rates)
      and outcomes were discounted at 3% per annum. A probabilistic sensitivity
      analysis was performed. RESULTS: In the base case, both the incremental cost
      utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of
      IFNbeta-1b versus no treatment were dominant (more effective and less costly)
      from a social perspective. From the perspective of the Spanish Health System, the
      ICUR was ? 40,702/QALY and the ICER was ? 13/relapse avoided. CONCLUSION: Early
      treatment with IFNbeta-1b after a CIS versus delayed treatment is efficient from
      a social perspective, but it may not be efficient from the perspective of the NHS
      which does not take non health-related costs into account.

PMID- 25976943
TI  - Effects of continuous positive airway pressure treatment on cognitive functions
      in patients with severe obstructive sleep apnoea.
AB  - INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) has numerous implications
      for health and can affect neurocognitive functions in patients. OBJECTIVE: To
      evaluate the neuropsychological functions most affected by OSAS, the factors
      associated with OSAS severity that are related to those functional limitations,
      and the effect of therapy with continuous positive airway pressure. PATIENTS AND
      METHOD: The sample consisted of 60 participants: 30 patients diagnosed with OSAS
      (clinical group) and 30 people without the disorder (control group). Memory,
      intellectual processes, and attention were analysed with selected subtests from
      the Luria-Nebraska neuropsychological battery (immediate memory, logical memory,
      intellectual processes, and attentional control subtests). RESULTS: Patients
      obtained significantly lower scores than controls in most of the areas evaluated.
      Associations were identified between subjective sleep quality and conceptual
      activity (r=-0.279; P<.05) and attentional control (r=-0.392; P<.01); between
      oxygen saturation and both immediate memory (r=0.296; P<.05) and thematic
      drawings (r=0.318; P<.05); and between apnoea-hypopnoea index and immediate
      memory (r=-0.303; P<.05), logical memory (r=-0.359; P<.01), and thematic drawings
      (r=-0.302; P<.05). Continuous positive airway pressure was shown to be effective
      (P=.03) only for improving immediate memory in patients with OSAS. CONCLUSIONS:
      Patients with severe OSAS showed memory and attentional limitations, associated
      with poorer quality of sleep and with worst AHI and SaO2 mean. The CPAP use
      improved memory of the patients evaluated.

PMID- 25976944
TI  - Cardiac arrhythmias in stroke unit patients. Evaluation of the cardiac monitoring
      data.
AB  - INTRODUCTION: Cardiac arrhythmias are frequent in acute stroke. Stroke units are
      widely equipped with cardiac monitoring systems. Pre-existing heart diseases and
      heart-brain interactions may be implicated in causing cardiac arrhythmias in
      acute stroke. This article analyses cardiac arrhythmias detected in patients
      hospitalised in a stroke unit. METHOD: Prospective observational study of
      consecutive patients admitted to a stroke unit with cardiac monitoring. We
      collected clinical data from patients and the characteristics of their cardiac
      arrhythmias over a 1-year period (2013). Time of arrhythmia onset, associated
      predisposing factors, and the therapeutic decisions made after detection of
      arrhythmia were examined. All patients underwent continuous cardiac monitoring
      during no less than 48hours. RESULTS: Of a total of 332 patients admitted,
      significant cardiac arrhythmias occurred in 98 patients (29.5%) during their stay
      in the stroke unit. Tachyarrhythmia (ventricular tachyarrhythmias,
      supraventricular tachyarrhythmias, complex ventricular ectopy) was present in 90
      patients (27.1%); bradyarrhythmia was present in 13 patients (3.91%). Arrhythmias
      were independently associated with larger size of brain lesion and older age. In
      10% of the patient total, therapeutic actions were taken after detection of
      significant cardiac arrhythmias. Most events occurred within the first 48hours
      after stroke unit admission. CONCLUSIONS: Systematic cardiac monitoring in
      patients with acute stroke is useful for detecting clinically relevant cardiac
      arrhythmias. Incidence of arrhythmia is higher in the first 48hours after stroke
      unit admission. Age and lesion size were predicted appearance of arrhythmias.
      Detection of cardiac arrhythmias in a stroke unit has important implications for
      treatment.

PMID- 25976945
TI  - Influenza A virus: A possible trigger factor for hypnic headache?

PMID- 25976946
TI  - Neural substrates of decision-making.
AB  - INTRODUCTION: Decision-making is the process of selecting a course of action from
      among 2 or more alternatives by considering the potential outcomes of selecting
      each option and estimating its consequences in the short, medium and long term.
      The prefrontal cortex (PFC) has traditionally been considered the key neural
      structure in decision-making process. However, new studies support the hypothesis
      that describes a complex neural network including both cortical and subcortical
      structures. OBJECTIVE: The aim of this review is to summarise evidence on the
      anatomical structures underlying the decision-making process, considering new
      findings that support the existence of a complex neural network that gives rise
      to this complex neuropsychological process. DEVELOPMENT: Current evidence shows
      that the cortical structures involved in decision-making include the
      orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral
      prefrontal cortex (DLPFC). This process is assisted by subcortical structures
      including the amygdala, thalamus, and cerebellum. CONCLUSIONS: Findings to date
      show that both cortical and subcortical brain regions contribute to the decision
      making process. The neural basis of decision-making is a complex neural network
      of cortico-cortical and cortico-subcortical connections which includes subareas
      of the PFC, limbic structures, and the cerebellum.

PMID- 25976947
TI  - Balo concentric sclerosis: A presentation mimicking ischaemic stroke.

PMID- 25976948
TI  - Pharmacogenetics of adverse reactions to antiepileptic drugs.
AB  - INTRODUCTION: Adverse drug reactions (ADRs) are a major public health concern and
      a leading cause of morbidity and mortality in the world. In the case of
      antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment
      since they decrease treatment adherence and impact patients' quality of life of
      patients. Pharmacogenetics aims to identify genetic polymorphisms associated with
      drug safety. This article presents a review of genes coding for drug metabolising
      enzymes and drug transporters, and HLA system genes that have been linked to AED
      induced ADRs. DEVELOPMENT: To date, several genetic variations associated with
      drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes
      with decreased activity, have been linked to phenytoin (PHT)-induced
      neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine
      (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2
      genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles
      (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs.
      CONCLUSIONS: Published findings show that there are ADRs with a pharmacogenetic
      basis and a high interethnic variability, which indicates a need for future
      studies in different populations to gather more useful results for larger number
      of patients. The search for biomarkers that would allow predicting ADRs to AEDs
      could improve pharmacotherapy for epilepsy.

PMID- 25976949
TI  - Epigenetic changes in neurology: DNA methylation in multiple sclerosis.
AB  - INTRODUCTION: Epigenetics is defined as the study of the mechanisms that regulate
      gene expression without altering the underlying DNA sequence. The best known is
      DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known
      etiology, in which it is stated that the involvement of environmental factors on
      people with a genetic predisposition, may be key to the development of the
      disease. It is at this intersection between genetic predisposition and
      environmental factors where DNA methylation may play a pathogenic role.
      DEVELOPMENT: A literature review of the effects of environmental risk factors for
      the development of MS can have on the different epigenetic mechanisms as well as
      the implication that such changes have on the development of the disease.
      CONCLUSION: Knowledge of epigenetic modifications involved in the pathogenesis of
      MS, opens a new avenue of research for identification of potential biomarkers, as
      well as finding new therapeutic targets.

PMID- 25976950
TI  - Reply.

PMID- 25976953
TI  - In memoriam. Carol Briggs.

PMID- 25976951
TI  - Vitamin D metabolites and bone mineral density: The multi-ethnic study of
      atherosclerosis.
AB  - Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D)
      concentrations with low bone mineral density (BMD) and fractures, motivating
      widespread use of vitamin D supplements for bone health. However, previous
      studies have been limited to predominantly White populations despite differences
      in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined
      associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH2)D3), and
      parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi
      Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study
      design. Vitamin D metabolites were measured using liquid chromatography-mass
      spectroscopy and PTH using a 2-site immunoassay from serum collected in 2000
      2002. Volumetric trabecular lumbar BMD was measured from computed tomography
      scans performed in 2002-2005 expressed as g/cm(3). We used linear regression and
      graphical methods to compare associations of vitamin D metabolite and PTH
      concentrations with BMD as the outcomes measure among White (n=714), Black
      (n=353), Chinese (n=249), and Hispanic (n=457) participants. Serum 25(OH)D and
      24,25(OH2)D3 concentrations were highest among Whites and lowest among Blacks.
      BMD was greatest among Black participants. Higher serum 25(OH)D was only
      associated with higher BMD among Whites and Chinese participants (P-for
      interaction=0.054). Comparing the lowest category of 25(OH)D (<20 ng/ml) to the
      highest (>=30 ng/ml), the adjusted mean difference in BMD was -8.1g/cm3 (95% CI 
      14.8, -1.4) for Whites; -10.2g/cm3 (-20.4, 0.0) for Chinese vs. 8.8 g/cm3 (-2.8,
      20.5) for Black and -1.1g/cm3 (-8.3, 6.2) for Hispanic. Similar results were
      observed for serum 24,25(OH2)D3. Serum PTH was not associated with BMD. In a
      multi-ethnic population, associations of 25(OH)D with BMD were strongest among
      White and Chinese participants and null among Black and Hispanic participants.
      Further studies are needed to determine optimal biomarkers for bone health for
      multiple ethnic groups.

PMID- 25976954
TI  - The evolution of guidelines for the validation of flow cytometric methods.
AB  - The recent advances in the field of flow cytometry have resulted in
      instrumentation with increased capacity which is actually more user-friendly.
      Thus, the technology has become more valuable to research scientists, the
      pharmaceutical industry and clinical laboratories. The use of flow cytometry in
      regulated labs has been hampered by the challenges associated method validation
      and the lack of official guidance documents on the topic. Thus key stakeholders
      have published recommendation papers with the hope that these will be
      incorporated as official guidance documents. This review will focus on the
      achievements of the stakeholders and a high-level overview their recommendations.

PMID- 25976955
TI  - Laboratory diagnosis of von Willebrand disease.
AB  - Von Willebrand disease (VWD) is considered the most common inherited bleeding
      disorder and may also be the most difficult to diagnose. Clinical symptoms of VWD
      include predominantly mild mucosal bleeding; surgical bleeding may occur with
      specific challenges and joint bleeding can occur in the most severe forms. A
      family history either of diagnosed VWD or of bleeding symptoms is typically
      present. Laboratory diagnosis requires a series of assays of von Willebrand
      factor (VWF) quantity and function, and factor VIII activity, with no single
      straightforward diagnostic test available to either confirm or exclude the
      diagnosis. Newer assays of VWF function are becoming more available and useful in
      determining the laboratory diagnosis of VWD. 

PMID- 25976956
TI  - Laboratory testing for platelet function disorders.
AB  - Platelet function testing is both complex and labor intensive. A stepwise
      approach to the evaluation of patients with suspected platelet disorders will
      optimize the use of laboratory resources, beginning with an appropriate clinical
      evaluation to determine whether the bleeding is consistent with a defect of
      primary hemostasis. Bleeding assessment tools, evaluation of platelet counts, and
      review of peripheral blood cell morphology can aid the initial assessment. For
      patients requiring further laboratory testing, platelet aggregometry, secretion
      assays, and von Willebrand factor assays are the most useful next steps and will
      direct further specialized testing including flow cytometry, electron microscopy,
      and molecular diagnostics. Guidelines and recommendations for standardizing
      platelet function testing, with a particular focus on light transmission
      aggregometry, are available and can provide a template for clinical laboratories
      in establishing procedures that will optimize diagnosis and assure quality
      results. This review outlines an approach to platelet function testing and
      reviews testing methods available to clinical laboratories. 

PMID- 25976957
TI  - Epidemiology and diagnostic testing for hemochromatosis and iron overload.
AB  - Hemochromatosis is the most common genetic disease in northern European
      populations. Body iron stores progressively increase in most patients, which can
      lead to cirrhosis of the liver, hepatocellular carcinoma, heart failure,
      arthritis, and pigmentation. Simple blood tests such as the serum ferritin and
      transferrin saturation are useful to suggest the diagnosis which can be confirmed
      in most cases with a simple genetic test for the C282Y mutation of the HFE gene.
      However, these blood tests are often misinterpreted and there are rare patients
      with iron overload without HFE mutations. A diagnostic approach is presented
      based on a large referral practice and a population-based study (HEIRS) which
      screened for iron overload in 101,168 participants.

PMID- 25976959
TI  - Assembly and evaluation of an inventory of guidelines that are available to
      support clinical hematology laboratory practice.
AB  - INTRODUCTION: Practice guidelines provide helpful support for clinical
      laboratories. Our goal was to assemble an inventory of publically listed
      guidelines on hematology laboratory topics, to create a resource for laboratories
      and for assessing gaps in practice-focused guidelines. METHODS: PubMed and
      website searches were conducted to assemble an inventory of hematology laboratory
      focused guidelines. Exclusions included annual, technical, or collaborative study
      reports, clinically focused guidelines, position papers, nomenclature, and
      calibration documents. RESULTS: Sixty-eight guidelines were identified on
      hematology laboratory practice topics from 12 organizations, some as joint
      guidelines. The median year of publication was 2010 and 15% were >10 years old.
      Coagulation topics had the largest numbers of guidelines, whereas some areas of
      practice had few guidelines. A minority of guidelines showed evidence of periodic
      updates, as some organizations did not remove or identify outdated guidelines.
      CONCLUSIONS: This inventory of current practice guidelines will encourage
      awareness and uptake of guideline recommendations by the worldwide hematology
      laboratory community, with the International Society for Laboratory Hematology
      facilitating ongoing updates. There is a need to encourage best guideline
      development practices, to ensure that hematology laboratory community has
      current, high-quality, and evidence-based practice guidelines that cover the full
      scope of hematology laboratory practice.

PMID- 25976958
TI  - Polyphosphate, platelets, and coagulation.
AB  - While we have understood the basic outline of the enzymes and reactions that make
      up the traditional blood coagulation cascade for many years, recently our
      appreciation of the complexity of these interactions has greatly increased. This
      has resulted in unofficial 'revisions' of the coagulation cascade to include new
      amplification pathways and connections between the standard coagulation cascade
      enzymes, as well as the identification of extensive connections between the
      immune system and the coagulation cascade. The discovery that polyphosphate is
      stored in platelet dense granules and is secreted during platelet activation has
      resulted in a recent burst of interest in the role of this ancient molecule in
      human biology. Here we review the increasingly complex role of platelet
      polyphosphate in hemostasis, thrombosis, and inflammation that has been uncovered
      in recent years, as well as novel therapeutics centered on modulating
      polyphosphate's roles in coagulation and inflammation. 

PMID- 25976960
TI  - Assessing nonvitamin K antagonist oral anticoagulants (NOACs) in the laboratory.
AB  - Nonvitamin K antagonist oral anticoagulants (NOACs) are being used with
      increasing frequency due to their safety profile, ease of use, and given that
      therapeutic monitoring is not required. As these agents have only recently been
      FDA approved, their effect on routine and specialty coagulation assays is not
      well appreciated. This article discusses NOAC effect on routine coagulation
      assays and whether these assays can be used to estimate drug concentration as
      well as which assays are suitable to quantitate drug concentration in plasma.
      Also reviewed is the use of manufactured drug calibrators to determine reagent
      responsiveness and the effect of these agents on various special coagulation
      assays. 

PMID- 25976961
TI  - Pearls and pitfalls in factor inhibitor assays.
AB  - The proper performance and interpretation of factor inhibitor assays is a
      critical role for the hemostasis laboratory. Both false-positive and false
      negative inhibitor assays may be reported, leading to serious patient
      mismanagement. Knowledge and recognition of common causes of both false-positive
      and negative-results can aid in the identification of these potential pitfalls.
      Safeguards to reporting accurate factor inhibitor assays include initial
      characterization of the sample, using the Nijmegen modification, properly
      performing and interpreting an incubated mixing test in conjunction, and
      performing two dilutions for each dependent dilution in the factor inhibitor
      assay. 

PMID- 25976962
TI  - Molecular genetic evaluation of myeloproliferative neoplasms.
AB  - The classical myeloproliferative neoplasms (MPNs) consist of chronic myelogenous
      leukemia (CML) and the non-CML MPNs, polycythemia vera (PV), essential
      thrombocythemia (ET), and primary myelofibrosis (PMF). Molecular testing plays a
      crucial role in each of these disease entities. In this review, we discuss the
      role and caveats of BCR-ABL1 fusion transcript evaluation in CML diagnosis and
      monitoring, as well as ABL1 kinase mutation testing in the setting of tyrosine
      kinase inhibitor resistance. We also focus on JAK2, MPL, and CALR mutations in
      PV, ET, and PMF. 

PMID- 25976963
TI  - Challenging hemostasis scenarios in pediatric patients--two case studies.
AB  - Pediatric patients differ from adult patients in many clinical situations, and
      disorders of hemostasis and thrombosis are no exception. The current article
      presents clinical and laboratory features of two cases in which pediatric
      patients are evaluated for bleeding disorders. Discussion of the cases focuses on
      practical considerations for laboratorians. Review of these case studies
      highlights selected common and esoteric issues in pediatric hemostasis testing. 

PMID- 25976964
TI  - Kruppel-like factor 1: hematologic phenotypes associated with KLF1 gene
      mutations.
AB  - Kruppel-like factor 1 (KLF1) is a pleiotropic erythroid transcription factor that
      is essential for hematopoiesis. KLF1 mutations have been associated with severe
      hematologic disorders, including congenital dyserythropoietic anemia type IV
      (CDAN4) due to a dominant-negative missense mutation (c.973G>A, p.Glu325Lys) and
      transfusion-dependent hemolytic anemia in compound heterozygotes for loss-of
      function mutations. In addition, several benign hematologic conditions are due to
      KLF1 haploinsufficiency. Herein, we review the genotype-phenotype relationship
      associated with KLF1 mutations and discuss the utility of KLF1 gene testing in
      laboratory hematology. 

PMID- 25976966
TI  - Hepcidin and iron disorders: new biology and clinical approaches.
AB  - Hepatic hormone hepcidin is a principal regulator of iron homeostasis and a
      pathogenic factor in common iron disorders. Hepcidin deficiency causes iron
      overload in hereditary hemochromatosis and iron-loading anemias, whereas hepcidin
      excess causes or contributes to the development of iron-restricted anemia in
      inflammatory diseases, infections, some cancers, and chronic kidney disease.
      Because of this, hepcidin may become a useful tool for diagnosis and management
      of iron disorders. Furthermore, a number of strategies that target hepcidin, its
      receptor, and its regulators are under development as novel therapeutic
      approaches for diseases associated with iron dysregulation. 

PMID- 25976965
TI  - Disorders of erythrocyte volume homeostasis.
AB  - Inherited disorders of erythrocyte volume homeostasis are a heterogeneous group
      of rare disorders with phenotypes ranging from dehydrated to overhydrated
      erythrocytes. Clinical, laboratory, physiologic, and genetic heterogeneities
      characterize this group of disorders. A series of recent reports have provided
      novel insights into our understanding of the genetic bases underlying some of
      these disorders of red cell volume regulation. This report reviews this progress
      in understanding determinants that influence erythrocyte hydration and how they
      have yielded a better understanding of the pathways that influence cellular water
      and solute homeostasis. 

PMID- 25976967
TI  - Quality of factor XI activity testing in North American Specialized Coagulation
      Laboratories.
AB  - INTRODUCTION: The performance of factor XI activity (FXI) by laboratories in the
      North American Specialized Coagulation Laboratory Association proficiency testing
      program was analyzed. METHODS: Over 10 years (2003-2013), 80 samples were
      distributed; 33-55 laboratories participated per exercise providing 3833 total
      responses. Analysis was performed on numeric results and qualitative
      classification of results. RESULTS: The sample FXI levels ranged from 3.8 to
      154.0 IU/dL. The overall interlaboratory average coefficient of variation (CV%)
      was 17.5%; the CV was higher for a sample with low (3.8 IU/dL) FXI. Results were
      correctly classified as abnormal (100%) for a sample with 3.8 IU/dL FXI and
      normal/borderline normal (97.7%) for 45 samples with 80 to < 140 IU/dL FXI. The
      classification was heterogeneous for samples with FXI of 50 to < 80 IU/dL. Six
      specimens were repeat-tested from 2007 to 2013. The mean FXI was not
      significantly different in laboratories using the same method on both exercises,
      suggesting good intralaboratory precision over time. Univariate analysis of data
      from 2011 to 2012 did not find a consistent significant difference among the
      activators, analyzers, calibrators, and FXI-deficient plasmas. CONCLUSION:
      Laboratories generally performed well in assessment of FXI based on
      interlaboratory precision when FXI >30 IU/dL and on classification of samples
      with very low or normal FXI.

PMID- 25976968
TI  - Advances in the pathogenesis and diagnosis of multiple myeloma.
AB  - Multiple myeloma (MM) is a tumor of indolent, bone marrow (BM) localized, isotype
      switched plasma cells. Recently, the diagnostic criteria have been amended to
      include some patients who would previously have been diagnosed with ultra-high
      risk smoldering MM and benefit from immediate treatment. Genetically it can be
      divided into tumors with different recurrent immunoglobulin heavy chain gene
      translocations (4p16, 11q13, 6p21, 16q23, 20q11) and tumors characterized by
      hyperdiploidy with multiple trisomies. Recent genomic studies have shown that
      almost half of untreated patients have a genetic rearrangements of the MYC locus
      that result in juxtaposition of ectopic super-enhancers adjacent to MYC, as well
      as somatic mutations that activate the RAS/MAPK pathway (NRAS, KRAS, BRAF,
      FGFR3). Mutations that result in constitutive activation of the NFkB pathway and
      that inactivate TP53, CDKN2C, KDM6A, FAM46C, and DIS3 are also recurrent. A major
      insight from these studies has been the recognition of the high degree of
      subclonal heterogeneity in MM, which is more frequent in patients with high-risk
      genetics. The subclones may alternate in dominance under alternating therapeutic
      pressure, a phenomenon known as 'clonal tides'. The identification of marked
      subclonal heterogeneity argues in those patients for the use of therapeutic
      strategies to maximize response, and long-term suppressive therapies to prevent
      tumor regrowth and development of additional subclones. 

PMID- 25976969
TI  - The utility of next-generation sequencing in diagnosis and monitoring of acute
      myeloid leukemia and myelodysplastic syndromes.
AB  - Myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic
      syndromes (MDS) are a heterogeneous group of disorders that share a common
      biology and are a major source of morbidity and mortality. In the last several
      years, studies using next-generation sequencing (NGS) have identified a core set
      of recurrently mutated myeloid malignancy genes in the majority of patients with
      AML and MDS, including those with normal cytogenetics. DNA-level mutations in
      several of these genes including NPM1, FLT3, and CEBPA in AML and ASXL1, ETV6,
      EZH2, RUNX1, and TP53 in MDS are associated with changes in patient outcomes and
      are now tested for in clinical laboratories. In addition to providing prognostic
      information, these gene mutations can be used to monitor patient disease burden
      through the use of ultrasensitive detection techniques. In this review, we will
      focus on the clinical utility of various NGS-based methods including whole-genome
      sequencing, exome sequencing, and targeted panel-based sequencing in the initial
      diagnosis and management of AML and MDS and cover recent methodological advances
      for the molecular monitoring of AML and MDS. 

PMID- 25976970
TI  - The diagnostic and clinical impact of genetics and epigenetics in acute myeloid
      leukemia.
AB  - Acute myeloid leukemia (AML) is a complex disease, for which our understanding of
      the role of genetic and epigenetic changes has undergone significant
      advancements. Newer diagnostic and prognostic classifications have increasingly
      incorporated such information, and novel therapies have been developed to target
      specific genes, processes, and pathways based on this growing understanding.
      Given the rapid evolution of this field, it is critical for physicians and
      translational researchers to have a more in-depth understanding of this evolving
      landscape. Here, we review both genetics and epigenetics in acute myeloid
      leukemia from a practical standpoint. 

PMID- 25976971
TI  - Flow cytometry immunophenotyping in integrated diagnostics of patients with newly
      diagnosed cytopenia: one tube 10-color 14-antibody screening panel and 3-tube
      extensive panel for detection of MDS-related features.
AB  - Acute leukemia, myelodysplastic syndromes (MDS), myeloproliferative neoplasms and
      lymphomas are the most prevalent diagnoses in adults presenting with new onset
      cytopenia. Here, we describe two 10-color panels of surface markers (screening
      and comprehensive panel) applied at the Flow Cytometry Laboratory, University
      Health Network, Toronto, ON, Canada. A 10-color flow cytometry is applied using
      the stain-lyse-wash sample preparation method. In patients with <10% blasts and
      no clear involvement by hematological malignancy based on cytomorphological
      evaluation of bone marrow (BM) smear, the recently published one-tube 10-color 14
      antibody screening panel is applied. This panel allows detection of major B- and
      T-cell abnormalities, enumeration of cells in blast region (CD45 dim), and gives
      insight into myeloid BM compartment, including calculation of four-parameter
      score for MDS-related abnormalities. In patients who present with >=10 - <20%
      blasts in blood or BM smears, a comprehensive three-tube panel of surface markers
      is used up front. The analysis is focused on the detection of abnormal antigen
      expression patterns not seen in normal/reactive BM, according to the guidelines
      developed by International/European LeukemiaNet Working Group for Flow Cytometry
      in MDS. In patients with >=20% blasts, an additional tube is added to allow the
      detection of cytoplasmic markers necessary to diagnose mixed phenotype acute
      leukemia. 

PMID- 25976972
TI  - Identifying and managing common childhood language and speech impairments.

PMID- 25976973
TI  - Versatile pulse sequence device to conserve hyperpolarization for NMR and MRI
      studies.
AB  - PURPOSE: Levitt and co-workers have described the M2S pulse sequence which
      transfers between longitudinal and singlet spin order. Building on this work, we
      describe the construction of a portable M2S pulse sequence generator to increase
      the relaxation time of polarized compounds. Additionally, we investigate the
      efficiency of spin order transfer under conditions where physical parameters of
      the system are not known precisely. THEORY AND METHODS: A portable M2S generator
      is built. Longitudinally polarized N2O is converted to the singlet state by both
      adiabatic transfer and by the M2S sequence. Density matrix simulations are used
      to model the effects of mismatched chemical shift, flip angle, and scalar
      couplings. RESULTS: Density matrix simulations suggest that to convert 95% of the
      longitudinal m = 1 triplet state population to the singlet order we must match
      the Larmor precession frequency to the excitation radiofrequency field by 10%,
      the scalar couplings must be determined to better than 0.6%, and the flip angle
      must be calibrated to better than 2%. CONCLUSION: The sequence is robust against
      many mismatched physical parameters of the species we are converting.
      Additionally, the instrument's portability allows for the conversion of
      hyperpolarized species near a polarizer. The lifetime is increased by ~12-fold.
      This is highly advantageous in systems where the hyperpolarized media relax
      rapidly.

PMID- 25976975
TI  - The prevention of diabetes and cardiovascular disease in people with
      schizophrenia.
AB  - OBJECTIVE: Primary prevention of diabetes and cardiovascular disease is an
      important priority for people with schizophrenia. This review aims to identify
      lifestyle and pharmacological interventions that reduce diabetes and
      cardiovascular disease in people with schizophrenia. METHOD: PubMed and other
      electronic databases were searched to identify relevant articles. RESULTS:
      Lifestyle interventions that focus on diet and physical activity reduce the
      incidence of diabetes. Similar programmes in people with schizophrenia have led
      to significant weight loss and may reasonably be expected to reduce diabetes in
      the long-term. Metformin may be considered when lifestyle change is not feasible
      or effective. Lifestyle interventions, particularly smoking cessation, are likely
      to be effective in reducing cardiovascular disease in people with schizophrenia.
      Although cardiovascular prevention trials with statins have not been performed in
      people with schizophrenia, similar reductions in cholesterol has been seen as in
      the general population and statins should be considered for those at high risk.
      Traditional cardiovascular risk prediction models perform well in identifying
      those at high cardiovascular risk, but bespoke prediction models using data from
      people with schizophrenia perform better. CONCLUSION: Reducing diabetes and
      cardiovascular disease requires a coordinated and concerted effort from mental
      and physical health teams working across primary and secondary care.

PMID- 25976974
TI  - Sequencing and expression analysis of salt-responsive miRNAs and target genes in
      the halophyte smooth cordgrass (Spartina alternifolia Loisel).
AB  - MicroRNAs have been shown to be involved in regulating plant's response to
      environmental stresses, including salinity. There is no report yet on the miRNA
      mediated posttranscriptional regulation of salt stress response of a grass
      halophyte by miRNAs. Here we report on the deep-sequencing followed by expression
      validation through (s)qRT-PCR of a selected set of salt-responsive miRNAs and
      their targets of the salt marsh monocot halophyte smooth cordgrass (Spartina
      alterniflora Loisel). Expression kinetics study of 12 miRNAs showed differential
      up/down-regulation in leaf and root tissues under salinity. Induction of
      expression of six putative novel microRNAs with high read counts in the sequence
      library suggested that the halophyte grass may possess different/novel gene
      posttranscriptional regulation of its salinity adaptation. Similarly, expression
      analysis of target genes of four selected miRNAs showed temporal and spatial
      variation in the up/down-regulation of their transcript accumulation under salt
      stress. The expression levels of miRNAs and their respective targets were
      coherent, non-coherent, or semi-coherent type. Understanding the gene regulation
      mechanism(s) at the miRNA level will broaden our fundamental understanding of the
      biology of the salt stress tolerance of the halophyte and provide novel positive
      regulators of salt stress tolerance for downstream research. 

PMID- 25976976
TI  - Onapristone (ZK299) and mifepristone (RU486) regulate the messenger RNA and
      protein expression levels of the progesterone receptor isoforms A and B in the
      bovine endometrium.
AB  - The aim of this study was to examine whether progesterone (P(4)) and its
      antagonists, onapristone (ZK299) and mifepristone (RU486), affect the levels of
      PGRA and PGRB messenger RNA (mRNA) and protein in the cow uterus which may be
      important in understanding whether the final physiological effect evoked by an
      antagonist depends on PGR isoform bound to the antagonist. Endometrial slices on
      Days 6 to 10 and 17 to 20 of the estrous cycle were treated for 6 or 24 hours for
      mRNA and protein expression analysis, respectively, with P4, ZK299, or RU486 at a
      dose of 10(-4), 10(-5), or 10(-6) M. In the samples on Days 6 to 10 of the
      estrous cycle, PGRAB mRNA was stimulated by P(4) (10(-4) M; P < 0.01) and RU486
      (10(-6); P < 0.001) and was decreased by ZK299 (10(-5); P < 0.05). In contrast,
      PGRB mRNA was decreased by the all P(4) (P < 0.01) and ZK299 (P < 0.001) doses
      and by two of the RU486 doses (10(-4) M; P < 0.01 and 10(-5) M; P < 0.01). In
      samples on Days 17 to 20 of the estrous cycle, PGRAB mRNA was stimulated by RU486
      (10(-5) M; P < 0.001). PGRB mRNA was decreased by P(4) (10(-4) and 10(-5) M; P <
      0.001), ZK299 (10(-4) and 10(-5) M; P < 0.001), and RU486 (10(-4) M; P < 0.01 and
      10(-6) M; P < 0.001) and was increased by ZK299 (10(-6) M; P < 0.001) and RU486
      (10(-5) M; P < 0.001). In samples on Days 6 to 10 of the estrous cycle, PGRB
      protein levels were decreased (P < 0.05) by all three ZK299 doses and by two of
      the RU486 doses (10(-4) M; P < 0.05 and 10(-5) M; P < 0.01). In contrast, in
      samples on Days 17 to 20, both PGRA and PGRB protein levels were decreased by
      ZK299 stimulation (10(-5) M; P < 0.05 and 10(-5) M; P < 0.01, respectively),
      whereas only PGRA protein levels were increased by RU486 (10(-5) M; P < 0.01).
      Both ZK299 and RU486 may exhibit both agonist and antagonist properties depending
      on which receptor isoform they affect. As a result, an increase or decrease in
      the expression of a particular PGR isoform will be observed.

PMID- 25976977
TI  - Expression and prognostic significance of VEGFR-2 in breast cancer.
AB  - Breast cancer is one of the most common cancers among women in the world.
      Vascular endothelial growth factor receptor 2 (VEGFR-2) was not only found to
      play a key role in the development of tumor angiogenesis, but has also been
      located in tumor cells of a variety of tumors. This study investigated the
      expression pattern of VEGFR-2 in breast cancer tissue specimens in order to
      evaluate the role of VEGFR-2 in the prognosis of breast cancer. Expression and
      localization of VEGFR-2 in tumor cells of breast cancer specimens from 98
      invasive breast cancer patients were determined by immunohistochemistry. The
      relationships between VEGFR-2 expression and clinicopathological features were
      also analyzed. The results showed that VEGFR-2 expression correlated positively
      with lymph node (LN) metastasis of breast cancer. Patients with high expression
      of VEGFR-2 had a significantly worse OS. It was also observed that the expression
      of epithelial-mesenchymal transition (EMT) marker, including Twist1 and Vimentin,
      was higher in the tumors with higher VEGFR-2 expression, while the E-cadherin
      expression was lower in the same tumors, suggesting that VEGFR-2 may serve as a
      possible mediator of EMT in breast cancer. 

PMID- 25976979
TI  - Pain interference in youth with neurofibromatosis type 1 and plexiform
      neurofibromas and relation to disease severity, social-emotional functioning, and
      quality of life.
AB  - The physical manifestations of neurofibromatosis type 1 (NF1) can cause chronic
      pain. This study investigated the impact of pain in youth with NF1 and plexiform
      neurofibromas (PNs) and its relationship to disease factors, social-emotional
      functioning, and quality of life (QOL) within a biopsychosocial framework.
      Caregivers of 59 children and adolescents with NF1 and PNs (6-18 years), and 41
      of these youth (10-18 years), completed questionnaires assessing social-emotional
      functioning and QOL, including an item on pain interference. Measures of disease
      severity included total PN volume by percent body weight and number of disease
      complications. Both caregiver (73%) and self-report (59%) ratings indicated that
      pain interferes with the child's daily functioning despite 33% taking pain
      medication. Based on caregivers' behavior ratings, more symptoms of anxiety and
      larger tumor volumes predicted greater pain interference, while greater pain
      interference, worse depressive symptoms, and more disease complications predicted
      poorer QOL. As rated by adolescents, more symptoms of anxiety predicted greater
      pain interference, while greater pain interference and social stress predicted
      poorer QOL. Further, social-emotional problems mediate the relationship between
      pain interference and QOL. Thus, pain interferes with daily functioning in the
      majority of youth with NF1 and PNs even when using pain medication. The impact of
      pain interference, disease severity, and particularly social-emotional problems
      on QOL highlights the interaction between physical and psychological states in
      NF1. Future research and treatment of pain in this population should utilize a
      biopsychosocial approach and involve multidisciplinary therapies including
      psychological interventions that target social-emotional functioning.

PMID- 25976978
TI  - Real-time monitoring of cell protrusion dynamics by impedance responses.
AB  - Cellular protrusions are highly dynamic structures involved in fundamental
      processes, including cell migration and invasion. For a cell to migrate, its
      leading edge must form protrusions, and then adhere or retract. The spatial and
      temporal coordination of protrusions and retraction is yet to be fully
      understood. The study of protrusion dynamics mainly relies on live-microscopy
      often coupled to fluorescent labeling. Here we report the use of an alternative,
      label-free, quantitative and rapid assay to analyze protrusion dynamics in a cell
      population based on the real-time recording of cell activity by means of
      electronic sensors. Cells are seeded on a plate covered with electrodes and their
      shape changes map into measured impedance variations. Upon growth factor
      stimulation the impedance increases due to protrusive activity and decreases
      following retraction. Compared to microscopy-based methods, impedance
      measurements are suitable to high-throughput studies on different cell lines,
      growth factors and chemical compounds. We present data indicating that this assay
      lends itself to dissect the biochemical signaling pathways controlling adhesive
      protrusions. Indeed, we show that the protrusion phase is sustained by actin
      polymerization, directly driven by growth factor stimulation. Contraction instead
      mainly relies on myosin action, pointing at a pivotal role of myosin in
      lamellipodia retraction. 

PMID- 25976980
TI  - Development of a District-Level Programmatic Assessment Tool for Risk of Measles
      Virus Transmission.
AB  - All six World Health Organization (WHO) regions have now set goals for measles
      elimination by or before 2020. To prioritize measles elimination efforts and use
      available resources efficiently, there is a need to identify at-risk areas that
      are offtrack from meeting performance targets and require strengthening of
      programmatic efforts. This article describes the development of a WHO measles
      programmatic risk assessment tool to be used for monitoring, guiding, and
      sustaining measles elimination efforts at the subnational level. We outline the
      tool development process; the tool specifications and requirements for data
      inputs; the framework of risk categories, indicators, and scoring; and the risk
      category assignment. Overall risk was assessed as a function of indicator scores
      that fall into four main categories: population immunity, surveillance quality,
      program performance, and threat assessment. On the basis of the overall score,
      the tool assigns each district a risk of either low, medium, high, or very high.
      The cut-off criteria for the risk assignment categories were based on the
      distribution of scores from all possible combinations of individual indicator
      cutoffs. The results may be used for advocacy to communicate risk to
      policymakers, mobilize resources for corrective actions, manage population
      immunity, and prioritize programmatic activities. Ongoing evaluation of
      indicators will be needed to evaluate programmatic performance and plan risk
      mitigation activities effectively. The availability of a comprehensive tool that
      can identify at-risk districts will enhance efforts to prioritize resources and
      implement strategies for achieving the Global Vaccine Action Plan goals for
      measles elimination.

PMID- 25976981
TI  - Coagulation factor IX regulates cell migration and adhesion in vitro.
AB  - Coagulation factor IX is thought to circulate in the blood as an inactive zymogen
      before being activated in the coagulation process. The effect of coagulation
      factor IX on cells is poorly understood. This study aimed to evaluate the effects
      of intact coagulation factor IX and its cleavage fragments on cell behavior. A431
      cells (derived from human squamous cell carcinoma), Pro5 cells (derived from
      mouse embryonic endothelial cells), Cos7 cells, and human umbilical vein
      endothelial cells were utilized in this study. The effects of coagulation factor
      IX and its cleavage fragments on cell behavior were investigated in several types
      of experiments, including wound-healing assays and modified Boyden chamber
      assays. The effect of coagulation factor IX depended on its processing; full
      length coagulation factor IX suppressed cell migration, increased adhesion to
      matrix, and enhanced intercellular adhesion. In contrast, activated coagulation
      factor IX enhanced cell migration, suppressed adhesion to matrix, and inhibited
      intercellular adhesion. An activation peptide that is removed during the
      coagulation process was found to be responsible for the activity of full-length
      coagulation factor IX, and the activity of activated coagulation factor IX was
      localized to an EGF domain of the coagulation factor IX light chain. Full-length
      coagulation factor IX has a sedative effect on cells, which is counteracted by
      activated coagulation factor IX in vitro. Thus, coagulation factor IX may play
      roles before, during, and after the coagulation process. 

PMID- 25976982
TI  - Babesia spp. in questing ticks from eastern Poland: prevalence and species
      diversity.
AB  - A total of 853 questing Ixodes ricinus males, females, and nymphs and of 582
      questing Dermacentor reticulatus males and females were collected from vegetation
      on the territory of the Lublin province (eastern Poland). The ticks were examined
      for the presence of Babesia by PCR detecting part of 18S ribosomal RNA (rRNA)
      gene and nuclear small subunit rRNA (SS-rDNA) for determining of Babesia spp. and
      Babesia microti, respectively. The overall incidence of Babesia strains in I.
      ricinus ticks was 4.6%. Three species of Babesia were identified. The prevalent
      species was B. microti which occurred in 2.8% of ticks, while Babesia venatorum,
      Babesia divergens, and unidentified Babesia species were found at the frequency
      of 1.2, 0.2, and 0.3%, respectively. Altogether, B. microti constituted 61.5% of
      the total strains detected in I. ricinus, B. venatorum-25.7%, B. divergens-5.1%,
      and unidentified Babesia species-7.7%. The prevalence of Babesia species in I.
      ricinus did not depend significantly on locality (chi(2) = 1.885, P = 0.390) nor
      on the tick stage (chi(2) = 4.874, P = 0.087). The incidence of Babesia strains
      in D. reticulatus ticks was 2.7%. Two species of Babesia were identified. Again,
      the prevalent species was B. microti which occurred in 2.1% of ticks, while B.
      canis was found in 0.7% of ticks. In one D. reticulatus female, B. canis and B.
      microti co-infection was found. Altogether, B. microti constituted 75% of the
      total strains detected in D. reticulatus while B. canis formed 25% of the total
      strains. The frequency of the occurrence of Babesia species in D. reticulatus did
      not depend significantly on locality (chi(2) = 0.463, P = 0.793). The difference
      between the prevalence of Babesia in males and females of D. reticulatus was
      insignificant (P = 0.0954); nymphs were not found. The dominance of B. microti in
      the species composition of tick-borne Babesia found in this study was typical for
      eastern Europe. In conclusion, the results revealed that the population
      inhabiting the forested area of eastern Poland could be exposed to Babesia
      parasites, especially to those from the species B. microti, by a bite of I.
      ricinus, a competent vector of human babesiosis, and probably also by a bite of
      D. reticulatus whose role in the transmission of human babesiosis needs to be
      clarified.

PMID- 25976984
TI  - Mechanism of camptocormia in Parkinson's disease analyzed by tilt table-EMG
      recording.
AB  - BACKGROUND: We previously classified camptocormia of Parkinson's disease (PD)
      into upper and lower types based on the inflection point, and reported
      improvement of upper camptocormia after lidocaine injection into the external
      oblique. However, the exact pathophysiology of this phenomenon remains obscure.
      METHODS: Surface electromyography (sEMG) was recorded in 11 PD patients with
      upper camptocormia, 11 PD patients with lower camptocormia, and 10 age-matched PD
      patients without postural deformity. Electrodes were positioned above the
      external oblique, hip flexors and paraspinal muscles at Th11 level bilaterally.
      Recording commenced with the patient in supine position on a tilt table, and
      continued when the table was tilted up to vertical position. Lidocaine was
      injected into the external oblique in patients with upper camptocormia and the
      psoas major in patients with lower camptocormia. RESULTS: All patients with upper
      and lower camptocormia developed the corresponding camptocormic posture during
      tilt up. The onset of camptocormic posture was preceded by the appearance of sEMG
      activity in the external oblique in 10 out of 11 patients with upper
      camptocormia, but less frequently in patients with lower camptocormia and the
      controls. Hip flexors sEMG activity was recorded in almost all patients. Posture
      was improved in 8 out of 9 patients with upper camptocormia, and 9 out of 11
      patients with lower camptocormia following injections of lidocaine. CONCLUSIONS:
      The results suggest the external oblique is involved, at least in part, in the
      development of upper camptocormia. Although EMG findings cannot differentiate
      pathogenicity, the psoas major is probably involved in lower camptocormia.

PMID- 25976983
TI  - Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after
      definitive radiotherapy.
AB  - Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG
      may alter their transcriptional activity. Thus, we determined the associations
      between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G,
      rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of
      recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the
      associations between FAS and FASLG genetic variants and the risk of recurrence in
      a cohort of 1,008 patients. The log-rank test and multivariate Cox models were
      used to evaluate the associations. Compared with patients with common homozygous
      genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes
      had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001,
      respectively) and an approximately threefold higher risk of SCCOP recurrence (HR,
      3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after
      multivariate adjustment. Furthermore, among patients with HPV16-positive tumors,
      those with variant genotypes of these two polymorphisms had lower disease-free
      survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher
      recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95%
      CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no
      significant associations were found for FAS1377 and FASLG124 polymorphisms. Our
      findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of
      recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger
      studies are needed to validate these results.

PMID- 25976985
TI  - Ethical safety of deep brain stimulation: A study on moral decision-making in
      Parkinson's disease.
AB  - INTRODUCTION: The possibility that deep brain stimulation (DBS) in Parkinson's
      disease (PD) alters patients' decisions and actions, even temporarily, raises
      important clinical, ethical and legal questions. Abnormal moral decision-making
      can lead to ethical rules violations. Previous experiments demonstrated the
      subthalamic (STN) activation during moral decision-making. Here we aim to study
      whether STN DBS can affect moral decision-making in PD patients. METHODS: Eleven
      patients with PD and bilateral STN DBS implant performed a computerized moral
      task in ON and OFF stimulation conditions. A control group of PD patients without
      DBS implant performed the same experimental protocol. All patients underwent
      motor, cognitive and psychological assessments. RESULTS: STN stimulation was not
      able to modify neither reaction times nor responses to moral task both when we
      compared the ON and the OFF state in the same patient (reaction times, p = .416)
      and when we compared DBS patients with those treated only with the best medical
      treatment (reaction times: p = .408, responses: p = .776). CONCLUSIONS: Moral
      judgment is the result of a complex process, requiring cognitive executive
      functions, problem-solving, anticipations of consequences of an action, conflict
      processing, emotional evaluation of context and of possible outcomes, and
      involving different brain areas and neural circuits. Our data show that STN DBS
      leaves unaffected moral decisions thus implying relevant clinical and ethical
      implications for DBS consequences on patients' behavior, on decision-making and
      on judgment ability. In conclusion, the technique can be considered safe on moral
      behavior.

PMID- 25976986
TI  - Bradykinesia induced by frequency-specific pallidal stimulation in patients with
      cervical and segmental dystonia.
AB  - INTRODUCTION: Pallidal deep brain stimulation (DBS) is an effective treatment for
      patients with primary dystonia leading to a substantial reduction of symptom
      severity. However, stimulation induced side effects such as bradykinesia have
      also been reported recently. The influence of stimulation parameters on such side
      effects have not yet been systemically assessed in these patients. METHODS: Here
      we tested the effect of stimulation frequency and duration of stimulation period
      on hand motor function in 22 patients with primary cervical and segmental
      dystonia using an unimanual tapping task. Patients performed the task at 4
      different stimulation frequencies (0 Hz = OFF stimulation, 20, 50 and >=130 Hz =
      high frequency stimulation) after either an SHORT (5 min, N = 16) or a LONG (60
      min, N = 6) stimulation period (i.e. changing of DBS-frequency). The change of
      overall mobility under HFS compared to the preoperative state was assessed with a
      5-point Likert-scale. Tapping performance was analysed using a repeated measures
      ANOVA with the main factor 'FREQUENCY'. Tapping performance at HFS and changes in
      general mobility were correlated using Spearman's Rho. RESULTS: We found a
      frequency specific modulation of hand motor function: HFS led to deterioration
      and 20 Hz stimulation to improvement of tapping rate. The effects were
      predominant in the 'LONG' group suggesting a significant contribution of
      stimulation duration. CONCLUSIONS: This is important to consider during DBS
      programming and evaluation of potential side effects. Furthermore, the impairment
      in hand motor function under HFS was mirrored by the patients' observation of a
      deterioration of general mobility.

PMID- 25976988
TI  - Reduced-intensity transplants, conventional transplants or chemotherapy for acute
      myeloid leukemia in 1st remission: who knows; ask your wife?

PMID- 25976987
TI  - NFATc1 as a therapeutic target in FLT3-ITD-positive AML.
AB  - Internal tandem duplications (ITD) in the Fms-related tyrosine kinase 3 receptor
      (FLT3) are associated with a dismal prognosis in acute myeloid leukemia (AML).
      FLT3 inhibitors such as sorafenib may improve outcome, but only few patients
      display long-term responses, prompting the search for underlying resistance
      mechanisms and therapeutic strategies to overcome them. Here we identified that
      the nuclear factor of activated T cells, NFATc1, is frequently overexpressed in
      FLT3-ITD-positive (FLT3-ITD+) AML. NFATc1 knockdown using inducible short hairpin
      RNA or pharmacological NFAT inhibition with cyclosporine A (CsA) or VIVIT
      significantly augmented sorafenib-induced apoptosis of FLT3-ITD+ cells. CsA also
      potently overcame sorafenib resistance in FLT3-ITD+ cell lines and primary AML.
      Vice versa, de novo expression of a constitutively nuclear NFATc1-mutant mediated
      instant and robust sorafenib resistance in vitro. Intriguingly, FLT3-ITD+ AML
      patients (n=26) who received CsA as part of their rescue chemotherapy displayed a
      superior outcome when compared with wild-type FLT3 (FLT3-WT) AML patients. Our
      data unveil NFATc1 as a novel mediator of sorafenib resistance in FLT3-ITD+ AML.
      CsA counteracts sorafenib resistance and may improve treatment outcome in AML by
      means of inhibiting NFAT.

PMID- 25976990
TI  - An electrochemical fungicide pyrimethanil sensor based on carbon nanotubes/ionic
      liquid construction modified electrode.
AB  - In this study, a simple, rapid, sensitive and environmentally friendly
      electroanalytical detection method for pyrimethanil (PMT) was developed, which
      was based on multi-walled carbon nanotubes (MWCNTs) and ionic liquids (IL) 1
      butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) modified glassy
      carbon electrode (GCE). MWCNTs-IL modified electrode significantly enhanced the
      oxidation peak current of PMT by combining the excellent electrochemical
      properties of MWCNTs and IL, suggesting that the modified electrode can
      remarkably improve the sensitivity of PMT detection. Under the optimum
      conditions, this electrochemical sensor exhibited a linear concentration range
      for PMT of 1.0 * 10(-7)-1.0 * 10(-4) mol L(-1) and the detection limit was 1.6 *
      10(-8) mol L(-1) (S/N = 3). The fabricated electrode showed good reproducibility,
      stability and anti-interference, and also it was successfully employed to detect
      PMT in real samples.

PMID- 25976989
TI  - Factors associated with in-hospital pulmonary embolism after shoulder
      arthroplasty.
AB  - BACKGROUND: Despite that pulmonary embolism (PE) is a feared complication after
      shoulder arthroplasty, little is known about its perioperative associated
      factors. MATERIALS AND METHODS: We used the Nationwide Inpatient Sample to gather
      a sample of 422,372 patients who underwent shoulder arthroplasty between 2002 and
      2011. This population was divided into 2 cohorts on the basis of those who
      experienced perioperative PE (0.25%) and those who did not. Demographics were
      compiled for both cohorts. Multivariable logistic regression analysis was used to
      account for confounding variables and to determine significant predictors of
      perioperative PE. RESULTS: After adjusting for patient demographic and clinical
      variables in multivariable regression modeling, the top 4 independent predictors
      for PE were primary diagnosis of proximal humerus fracture, deficiency anemia,
      congestive heart failure, and chronic lung disease. Other pertinent risk factors
      included increasing age, obesity, fluid and electrolyte abnormalities, undergoing
      total shoulder arthroplasty rather than hemiarthroplasty, and subsequent days of
      postoperative care. CONCLUSIONS: Knowledge of these factors might help in
      preoperative counseling and prove useful for implementation of quality
      improvement strategies to reduce the occurrence of PE. Surgeons may consider
      initiating thromboprophylaxis in patients with any of the aforementioned
      comorbidities.

PMID- 25976991
TI  - Stability of encapsulated beef-like flavourings prepared from enzymatically
      hydrolysed mushroom proteins with other precursors under conventional and
      microwave heating.
AB  - A comparative study was carried out between two beef-like flavourings prepared by
      conventional and microwave heating (CBF and MBF) of enzymatic hydrolysate of
      mushroom protein with other flavour precursors. GC-MS analysis of the isolated
      volatiles revealed that the thiol containing compounds were the predominate in
      both samples. However, MBF comprised higher concentration of these compounds
      (13.84 +/- 0.06%) than CBF (10.74 +/- 0.06%). The effect of microencapsulation
      with gum Arabic by using spray drying on the odour profile and volatile compounds
      of the two encapsulated samples (E-CBF and E-MBF) was investigated. The results
      revealed significant qualitative and quantitative variations in the volatiles of
      both samples. The highly volatile compounds decreased remarkably in concentration
      with encapsulation, while the pyrazines, thiazoles and disulphides showed
      opposite trend. The significant decrease in the thiol containing compounds in E
      CBF and E-MBF were attributed to their oxidation to other compounds such as
      disulphide compounds which showed significant increase in the encapsulated
      samples.

PMID- 25976992
TI  - Tailoring properties of natural deep eutectic solvents with water to facilitate
      their applications.
AB  - Previously it was demonstrated that natural deep eutectic solvents (NADES) are
      promising green solvents for the extraction of natural products. However, despite
      their potential, an obvious disadvantage of NADES is the high viscosity. Here we
      explored the dilution effect on the structures and physicochemical properties of
      NADES and their improvements of applications using quercetin and carthamin. The
      results of FT-IR and (1)H NMR experiments demonstrated that there are intensive H
      bonding interactions between the two components of NADES and dilution with water
      caused the interactions weaken gradually and even disappeared completely at
      around 50% (v/v) water addition. A small amount of water could reduce the
      viscosity of NADES to the range of water and increase the conductivity by up to
      100 times for some NADES. This study provides the basis for modulating NADES in a
      controllable way for their applications in food processing, enzyme reactions,
      pharmaceuticals and cosmetics. 

PMID- 25976993
TI  - Assessment of flavonoids and volatile compounds in tea infusions of water lily
      flowers and their antioxidant activities.
AB  - Water lily, a member of the Nymphaeaceae family, can be made into tea on the
      basis of outstanding fragrance characteristics and health care functions. In this
      study, 16 flavonoids were identified and quantified in tea infusions prepared
      from the petals of 33 water lily cultivars using HPLC-DAD and HPLC-ESI-MS/MS. The
      infusions were analyzed with HS-SPME coupled with GC-MS; 29 volatile compounds
      were detected, of which nine were found to be scent components. The cultivars
      were clustered into three clusters characterized according to scent components.
      The 'Conqueror' and 'Virginia' cultivars had the highest antioxidant activities.
      The concentrations of polyphenols and flavonoids showed significant positive
      correlations with antioxidant activity as measured by DPPH, ABTS(+), and FRAP
      assays. This study is valuable for a fuller understanding of this important tea
      and can also be used for the development of water lily. 

PMID- 25976994
TI  - Increased oxidative and nitrosative reactions during digestion could contribute
      to the association between well-done red meat consumption and colorectal cancer.
AB  - Uncured and nitrite-cured pork were subjected, raw, cooked (65  degrees C, 15
      min) or overcooked (90  degrees C, 30 min), to an in vitro digestion model, which
      includes mouth, stomach, duodenum, and colon phases. Heating of uncured meat
      resulted in a pronounced increase in lipid and protein oxidation products
      throughout digestion. Nitrite-curing had an antioxidant effect during digestion,
      but this effect disappeared when the meat was overcooked, resulting in up to
      ninefold higher 4-hydroxy-2-nonenal concentrations compared with digested nitrite
      cured raw and cooked pork. Colonic digesta contained significantly higher
      concentrations of the NOC-specific DNA adduct O(6)-carboxy-methylguanine when
      pork underwent a more intense heating procedure, independent of nitrite-curing,
      depending strongly on the fecal inoculum used. Since processed meats are usually
      nitrite-cured, the present study suggests that overcooking processed meat is
      likely to result in the formation of genotoxic compounds during digestion and
      should, therefore, be avoided.

PMID- 25976995
TI  - Isolation, purification and identification of antioxidants in an aqueous aged
      garlic extract.
AB  - An aqueous aged garlic extract (AGE) was prepared by soaking sliced garlic in
      water for 20days at room temperature (23-25  degrees C). In order to locate the
      antioxidant ingredients of the aqueous AGE, an activity-guided fractionation
      approach using ABTS assay, DPPH assay and FRAP assay were conducted to guide the
      fractionation by means of extraction, column chromatography and semi-preparative
      HPLC. Some phenols and organosulfur compounds were identified as antioxidants in
      AGE by GC-MS. Furthermore, UV, IR, ESI-MS, NMR and specific rotation experiments
      led to the identification of l-phenylalanine, l-tryptophan, (3S)-1,2,3,4
      tetrahydro-beta-carboline-3-carboxylic acid, (1S,3S)-1-methyl-1,2,3,4-tetrahydro
      beta-carboline-3-carboxylic acid, and (1R,3S)-1-methyl-1,2,3,4-tetrahydro-beta
      carboline-3-carboxylic acid as the major antioxidants in the AGE. The EC50 values
      of these purified tetrahydro-beta-carboline derivatives were 0.625-1.334 MUmol/mL
      and 1.063-2.072 MUmol/mL in ABTS assay and DPPH assay, respectively. It is the
      first time for us to identify (3S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic
      acid as an in vitro antioxidant in AGE.

PMID- 25976996
TI  - Approaches of aroma extraction dilution analysis (AEDA) for headspace solid phase
      microextraction and gas chromatography-olfactometry (HS-SPME-GC-O): Altering
      sample amount, diluting the sample or adjusting split ratio?
AB  - Aroma extract dilution analysis (AEDA) is widely used for the screening of aroma
      active compounds in gas chromatography-olfactometry (GC-O). In this study, three
      aroma dilution methods, (I) using different test sample volumes, (II) diluting
      samples, and (III) adjusting the GC injector split ratio, were compared for the
      analysis of volatiles by using HS-SPME-AEDA. Results showed that adjusting the GC
      injector split ratio (III) was the most desirable approach, based on the
      linearity relationships between Ln (normalised peak area) and Ln (normalised
      flavour dilution factors). Thereafter this dilution method was applied in the
      analysis of aroma-active compounds in Japanese soy sauce and 36 key odorants were
      found in this study. The most intense aroma-active components in Japanese soy
      sauce were: ethyl 2-methylpropanoate, ethyl 2-methylbutanoate, ethyl 3
      methylbutanoate, ethyl 4-methylpentanoate, 3-(methylthio)propanal, 1-octen-3-ol,
      2-methoxyphenol, 4-ethyl-2-methoxyphenol, 2-methoxy-4-vinylphenol, 2
      phenylethanol, and 4-hydroxy-5-ethyl-2-methyl-3(2H)-furanone. 

PMID- 25976997
TI  - Effect of the refining process on Moringa oleifera seed oil quality.
AB  - We evaluated the physicochemical properties and oxidative stability of the oil
      extracted from the seeds of Moringa oleifera during its refining process.
      Refining is accomplished in three stages: neutralization, degumming, and
      bleaching. Four samples were analyzed, corresponding to each step of the
      processed and crude oil. Increases in the density, viscosity, saponification
      value and oxidation of the oil were detected during the refining, while the
      peroxide value and carotenoid content diminished. Moreover, the refractive index
      and iodine content were stable throughout the refining. Nine fatty acids were
      detected in all four samples, and there were no significant differences in their
      composition. Oleic acid was found in the largest amount, followed by palmitic
      acid and behenic acid. The crude, neutralized, and degummed oils showed high
      primary oxidation stability, while the bleached oil had a low incidence of
      secondary oxidation. 

PMID- 25976998
TI  - A quadruplex PCR (qxPCR) assay for adulteration in dairy products.
AB  - This study describes the development of a quadruplex quantitative Real Time PCR
      (qxPCR) based on SYBR(r)GreenER chemistry, for rapid identification of DNA of
      cow, goat, sheep and buffalo in dairy products, and for quantification of cow DNA
      in these products. The platform was applied to: (i) mixes of milks at fixed
      percentages; (ii) cheeses prepared with the same mixes; (iii) commercial dairy
      products. The methodology enabled the detection of DNA from cow in mixes of milk
      and cheeses with a limit of detection (LOD) of 0.1%. When applied to commercial
      dairy products the qxPCR gave results comparable with each single-plex Real Time
      PCR. A good correlation (R(2)>0.9) between peaks' area of derivative of melting
      curves of amplicons and percentages of cow milk in milk mixes and cheeses, allows
      for an estimation of cow DNA in a dynamic range varying from 0.1-5% to 1-25%. 

PMID- 25976999
TI  - Antioxidant capacity and vitamin E in barley: Effect of genotype and storage.
AB  - Antioxidants, including vitamin E, may have a positive effect on human health and
      prolong storage of food items. Vitamin E content and antioxidant capacity were
      measured in 25 barley genotypes before and after 4 months storage at 10  degrees
      C using high performance liquid chromatography (HPLC) and ability to scavenge
      DPPH radicals, respectively. As expected, alpha-tocotrienol (alpha-T3) and alpha
      tocopherol (alpha-T) were the predominant tocol isomers. Vitamin E content and
      antioxidant capacity varied significantly among genotypes. Vitamin E ranged from
      8.5 to 31.5 MUg/g dry weight (DW) while ascorbic acid equivalent antioxidant
      capacity (AEAC) varied from 57.2 to 158.1 mg AEAC/100 g fresh weight (FW).
      Generally, lower vitamin E content or antioxidant capacity was observed in
      hulless or coloured genotypes. These results suggest that some genotypes are
      potential candidates for breeding of barley cultivars with high vitamin E content
      or antioxidant capacity at harvest, even after storage.

PMID- 25977000
TI  - Content evaluation of 4 furanocoumarin monomers in various citrus germplasms.
AB  - Due to the furanocoumarin compounds in the fruit, the production and consumption
      of grapefruit have been affected in the past decades since the 'grapefruit juice
      effect' was declared. To provide elite germplasm and obtain knowledge for future
      citrus breeding programs, the contents of 4 furanocoumarin monomers (FCMs) in the
      juice sacs from 73 citrus germplasms were evaluated using ultra-performance
      liquid chromatography. 6',7'-Dihydroxybergamottin and bergamottin were dominant
      in all the tested grapefruits, while there were some pomelos with dominant
      epoxybergamottin, and some with dominant 6',7'-dihydroxybergamottin and
      bergamottin. The contents of FCMs were low or below detection in sweet oranges,
      mandarins, lemons and trifoliate oranges. The results also show that the dominant
      patterns of FCMs are genotype-related, and crossing and selection are effective
      approaches to alter FCM profiles in citrus breeding. Furthermore, the
      contribution of pomelo as a parent to grapefruit regarding their FCM profiles was
      discussed. 

PMID- 25977001
TI  - Application of solvent-assisted dispersive solid phase extraction as a new, fast,
      simple and reliable preconcentration and trace detection of lead and cadmium ions
      in fruit and water samples.
AB  - In this research, a new sample treatment technique termed solvent-assisted
      dispersive solid phase extraction (SA-DSPE) was developed. The new method was
      based on the dispersion of the sorbent into the sample to maximize the contact
      surface. In this approach, the dispersion of the sorbent at a very low milligram
      level was achieved by injecting a mixture solution of the sorbent and disperser
      solvent into the aqueous sample. Thereby, a cloudy solution formed. The cloudy
      solution resulted from the dispersion of the fine particles of the sorbent in the
      bulk aqueous sample. After extraction, the cloudy solution was centrifuged and
      the enriched analytes in the sediment phase dissolved in ethanol and determined
      by flame atomic absorption spectrophotometer. Under the optimized conditions, the
      detection limit for lead and cadmium ions was 1.2 MUg L(-1) and 0.2 MUg L(-1),
      respectively. Furthermore, the preconcentration factor was 299.3 and 137.1 for
      cadmium and lead ions, respectively. SA-DSPE was successfully applied for trace
      determination of lead and cadmium in fruit (Citrus limetta, Kiwi and pomegranate)
      and water samples. Finally, the introduced sample preparation method can be used
      as a simple, rapid, reliable, selective and sensitive method for flame atomic
      absorption spectrophotometric determination of trace levels of lead and cadmium
      ions in fruit and water samples.

PMID- 25977002
TI  - Cell wall compounds of red grapes skins and their grape marcs from three
      different winemaking techniques.
AB  - Different winemaking practices are aimed at increasing cell wall degradation to
      facilitate extraction of valuables molecules into the wine. However, little
      attention has been paid to the composition of marcs from different cultivars
      according to the influence of the winemaking procedures. We provide information
      on skin cell walls from Cabernet Sauvignon, Syrah and Monastrell grapes and
      examine how different winemaking practices (addition of enzymatic preparation and
      beta-galactosidase separately and dry ice addition) may affect the composition of
      marc skin cell wall material (CWM). The efficiency of CWM isolation from the
      grape skin and also its composition is influenced by the cultivar. A similar
      cultivar influence has been detected on CWM from the marc, being the differences
      also due to the enological technique. Our results help to increase our knowledge
      on the degradation of cell walls during vinification, while providing a valuable
      guideline to upgrade the value of these by-products.

PMID- 25977003
TI  - Effects of single and dual physical modifications on pinhao starch.
AB  - Pinhao starch was modified by annealing (ANN), heat-moisture (HMT) or sonication
      (SNT) treatments. The starch was also modified by a combination of these
      treatments (ANN-HMT, ANN-SNT, HMT-ANN, HMT-SNT, SNT-ANN, SNT-HMT). Whole starch
      and debranched starch fractions were analyzed by gel-permeation chromatography.
      Moreover, crystallinity, morphology, swelling power, solubility, pasting and
      gelatinization characteristics were evaluated. Native and single ANN and SNT
      treated starches exhibited a CA-type crystalline structure while other modified
      starches showed an A-type structure. The relative crystallinity increased in ANN
      treated starches and decreased in single HMT- and SNT-treated starches. The ANN,
      HMT and SNT did not provide visible cracks, notches or grooves to pinhao starch
      granule. SNT applied as second treatment was able to increase the peak viscosity
      of single ANN- and HMT-treated starches. HMT used alone or in dual modifications
      promoted the strongest effect on gelatinization temperatures and enthalpy. 

PMID- 25977004
TI  - Tailoring physicochemical and sensorial properties of defatted soybean flour
      using jet-milling technology.
AB  - The effects of jet-milling on the physicochemical and sensorial properties of
      defatted soybean flour (DSF) were investigated. Superfine DSF powder (DSF-JM; D50
      = 4.3 +/- 0.1 MUm) was prepared from DSF powder (DSF-150; D50 = 257.0 +/- 1.7
      MUm) via conventional sifting followed by jet-milling. The jet-milled DSF showed
      significant increases in hydration properties, with increases in the water
      holding capacity, water-solubility index, and swelling capacity of 24%, 39%, and
      32%, respectively. Soluble dietary fibre and fat-binding capacity of DSF-JM also
      increased significantly (p < 0.05). A quantitative descriptive analysis by
      trained panelists indicated that the sensorial properties of DSF were also
      modified by jet milling. The DSF-JM showed significant reductions in bitterness
      and roughness, but sweetness increased, and the colour of DSF-JM changed to a
      brighter achromatic colour. These results indicate that superfine DSF could be an
      ingredient used to modify physical and sensorial properties of food.

PMID- 25977005
TI  - Ability of human oral microbiota to produce wine odorant aglycones from odourless
      grape glycosidic aroma precursors.
AB  - Grape aroma precursors are odourless glycosides that represent a natural
      reservoir of potential active odorant molecules in wines. Since the first step of
      wine consumption starts in the oral cavity, the processing of these compounds in
      the mouth could be an important factor in influencing aroma perception.
      Therefore, the objective of this work has been to evaluate the ability of human
      oral microbiota to produce wine odorant aglycones from odourless grape glycosidic
      aroma precursors previously isolated from white grapes. To do so, two
      methodological approaches involving the use of typical oral bacteria or the whole
      oral microbiota isolated from human saliva were followed. Odorant aglycones
      released in the culture mediums were isolated and analysed by HS-SPME-GC/MS.
      Results showed the ability of oral bacteria to hydrolyse grape aroma precursors,
      releasing different types of odorant molecules (terpenes, benzenic compounds and
      lipid derivatives). The hydrolytic activity seemed to be bacteria-dependent and
      was subject to large inter-individual variability. 

PMID- 25977006
TI  - Development of a quantitative method for the simultaneous analysis of the boar
      taint compounds androstenone, skatole and indole in porcine serum and plasma by
      means of ultra-high performance liquid chromatography coupled to high resolution
      mass spectrometry.
AB  - Boar taint is an off-odour occurring while heating meat or fat from boars. A
      method detecting the three compounds (androstenone, skatole and indole)
      simultaneously in blood would offer substantial advantages since it would allow
      monitoring the impact of rearing strategies. Therefore, a UHPLC-HR-Orbitrap-MS
      analysis method is optimized and validated for the quantification of these
      compounds in plasma or serum. Sample pre-treatment involved an extraction with
      diethylether followed by a centrifugal filtration (30 kDa). Limits of detection
      and quantification varied between 0.5 and 1 MUg L(-1) and 2 and 3 MUg L(-1) for
      the three compounds, respectively. Besides, an excellent repeatability (RSD <
      7.6%), within-laboratory reproducibility (RSD<10.5%), recovery (87-97%) and
      linearity (R(2)>0.99) were recorded. Correlations between serum/plasma and fat
      levels of the boar taint compounds were positive for skatole (r(serum) = 0.39 and
      r(plasma) = 0.84) and androstenone (r(serum) = 0.73-0.78 and r(plasma) = 0.32
      0.80).

PMID- 25977007
TI  - Chiral ligand-exchange separation and determination of malic acid enantiomers in
      apple juice by open-tubular capillary electrochromatography.
AB  - This study describes the application of an open tubular capillary column for
      chiral ligand-exchange separation and determination of malic acid enantiomers in
      apple juice by open-tubular capillary electrochromatography (OT-CEC). The open
      tubular column was prepared by in-situ grafting polymerization of 3-chloro-2
      hydroxypropyl methacrylate (HPMA-Cl) and followed by L-Histidine (L-His)
      modification. L-His was used as a chiral ligand-exchange selector and copper (II)
      as a central ion. The electrochromatographic characterization of the open tubular
      column was performed with the use of thiourea as an electroosmotic flow (EOF)
      marker. Factors affecting electrochromatographic enantioseparation of malic acid
      were also studied. The running buffer conditions for optimum enantioseparation of
      malic acid were found to be ACN/5.0mM CuSO4, 20.0mM (NH4)2SO4 (60/40%, v/v)
      adjusted to pH 3.0. The separation and determination of the enantiomers of malic
      acid in the apple juice solution diluted 10- to 40-folds were successfully
      achieved.

PMID- 25977008
TI  - Human exposure modelling of quercetin in onions (Allium cepa L.) following
      thermal processing.
AB  - Post-harvest treatment can influence levels of secondary metabolites in fruits
      and vegetables. Onions contain high levels of quercetin but are commonly heat
      treated before consumption. Hence, the objective of this study was to examine the
      effect of cooking treatments on the flavonoid (3,4'-Qdg and 4'-Qmg)
      concentrations in onion and to determine, by simulation modelling, probable human
      exposure. Onion samples (n=3) were cooked using three processes (fry, bake and
      steam) for three time intervals (5, 10 and 15 min). Frying (<10 min) was the
      ideal cooking method which retained concentrations of 3,4'-Qdg and 4'-Qmg at
      >50%. Thermal processing (>10 min) was shown to decrease quercetin content in all
      samples. The simulation model predicted human absorption and exposure. Steaming
      (15 min) resulted in the lowest quercetin exposure, with mean values of 4000 and
      400 MUg/day for 3,4'-Qdg and 4'-Qmg, respectively. Untreated onions had mean
      exposures of 14,000 and 3000 MUg/day for 3,4'-Qdg and 4'-Qmg, respectively.

PMID- 25977009
TI  - Quality changes of pasteurised orange juice during storage: A kinetic study of
      specific parameters and their relation to colour instability.
AB  - In view of understanding colour instability of pasteurised orange juice during
      storage, to the best of our knowledge, this study reports for the first time in a
      systematic and quantitative way on a range of changes in specific quality
      parameters as a function of time and as well as temperature (20-42  degrees C). A
      zero-order ( degrees Brix, fructose, glucose), a first-order (vitamin C), a
      second-order (sucrose) and a fractional conversion model (oxygen) were selected
      to model the evolution of the parameters between parentheses. Activation energies
      ranged from 22 to 136 kJ mol(-1), HMF formation being the most temperature
      sensitive. High correlations were found between sugars, ascorbic acid, their
      degradation products (furfural and HMF) and total colour difference (DeltaE(*)).
      Based on PLS regression, the importance of the quality parameters for colour
      degradation was ranked relatively among each other: the acid-catalysed
      degradation of sugars and ascorbic acid degradation reactions appeared to be
      important for browning development in pasteurised orange juice during ambient
      storage.

PMID- 25977010
TI  - Development of a chromatographic low pressure flow injection system using
      amperometric detection: Application to the analysis of niacin in coffee.
AB  - In this work, an analytical flow system able to perform low pressure
      chromatography with amperometric detection is presented. As case study, the
      determination of niacin (vitamin B3) in coffee brewed samples was selected. The
      manifold comprised a 1.0 cm length monolithic column coated with
      didecyldimethylammonium bromide, a laboratory-made boron doped diamond electrode,
      and featured in-line ionic strength adjustment of the mobile phase. The figures
      of merit concerning the selected case study namely, detection limit, 7.90 * 10(
      7) M, determination rate, ca. 10 samplesh(-1), mobile phase and ISA solution
      consumption, ca. 2.6 mL per analysis, and CV, below 5% for retention time and
      peak height, showed the competitiveness of this analytical strategy comparing to
      the described HPLC methods for niacin determination. The strategy displays a
      simple configuration, low cost, fast and easy assembling, foreseeing its use to
      general purpose applications.

PMID- 25977011
TI  - Novel HPLC--Fluorescence methodology for the determination of methylglyoxal and
      glyoxal. Application to the analysis of monovarietal wines "Ribera del Guadiana".
AB  - The determination and quantification of alpha-dicarbonyl compounds, glyoxal and
      methylglyoxal, in "Ribera del Guadiana" monovarietal wines (Extremadura, Spain)
      without sample clean-up has been carried out by HPLC with spectrofluorimetric
      detection (307/371 nm). For this purpose, a derivatization step with the new
      reagent 3,4-diaminopyridine at pH 2 during 120 min at 90  degrees C has been
      included. Afterwards, the sample could be injected in the chromatographic system
      with no clean-up, during a total run time of 4 min. Several monovarietal wines
      (white, rose and red) have been analyzed and the levels of these compounds for
      white wines were between 0.4-1.0 mg L(-1) glyoxal and 0.8-1.3 mg L(-1)
      methylglyoxal; and between 0.8-3.0 mg L(-1) and 0.5-1.8 mg L(-1) of glyoxal and
      methylglyoxal respectively, in red wines.

PMID- 25977012
TI  - Isolation and identification of minor secoiridoids and phenolic components from
      thermally treated olive oil by-products.
AB  - The application of an industrial process based on the hydrothermal treatment of
      160  degrees C/60 min of alperujo, a by-product of olive oil extraction, allows
      the formation of a liquid phase containing a high concentration of phenolic and
      secoiridoid compounds. Ethyl acetate was used to extract these phenolic compounds
      from the aqueous matrix. In this study, the isolation with polyamide and XAD
      resin allowed detection of the presence of phenolic compounds in minor
      concentrations. These minor phenols were several oleuropein derivatives that had
      not been identified in these phenolic extracts previously. The polar compounds,
      acteosides, secoiridoids, and flavonoids, that remain in the aqueous fraction
      after extraction with ethyl acetate were identified. We report the presence of
      known compounds and also detected a novel molecule in alperujo with a molecular
      weight of 408 whose structure was characterized for first time. This new
      secoiridoid glucoside was identified as 1-beta-D-glucopyranosyl
      acyclodihydroelenolic acid.

PMID- 25977013
TI  - Microencapsulation of betalains obtained from cactus fruit (Opuntia ficus-indica)
      by spray drying using cactus cladode mucilage and maltodextrin as encapsulating
      agents.
AB  - The microencapsulation of betalains from cactus fruit by spray drying was
      evaluated as a stabilization strategy for these pigments. The betalains used as
      active agent were extracted from purple fruits of Opuntia ficus-indica (BE) and
      encapsulated with maltodextrin and cladode mucilage MD-CM and only with MD. The
      microcapsulates were characterized by scanning electron microscopy (SEM), thermal
      analysis (TGA-DSC), tristimulus colorimetry, as well as, their humidity, water
      activity and dietary fiber content were also determined. The active agent content
      was measured by UV-Vis spectrophotometry and its composition confirmed by HPLC
      ESIMS. A pigment storage stability test was performed at 18  degrees C and
      different relative humidities. The addition of CM in the formulation increased
      the encapsulation efficiency, diminished the moisture content, and allowed to
      obtain more uniform size and spherical particles, with high dietary fiber
      content. These microencapsulates are promising functional additive to be used as
      natural colorant in the food industry.

PMID- 25977014
TI  - An innovative method for immobilizing sucrose isomerase on epsilon-poly-L-lysine
      modified mesoporous TiO2.
AB  - Sucrose isomerase (SIase) is the key enzyme in the enzymatic synthesis of
      isomaltulose. Mesoporous titanium dioxide (M-TiO2) and epsilon-poly-L-lysine
      functionalized M-TiO2 (EPL-M-TiO2) were prepared as carriers for immobilizing
      SIase. SIase was effectively immobilized on EPL-M-TiO2 (SI-EPL-M-TiO2) with an
      enzyme activity of 39.41 U/g, and the enzymatic activity recovery rate up to
      93.26%. The optimal pH and temperature of immobilized SIase were 6.0 and 30
      degrees  C, respectively. SI-EPL-M-TiO2 was more stable in pH and thermal tests
      than SIase immobilized on M-TiO2 and free SIase. K(m) of SI-EPL-M-TiO2 was 204.92
      mmol/L, and vmax was 45.7 MUmol/L/s. Batch catalysis reaction of sucrose by SI
      EPL-M-TiO2 was performed under the optimal conditions. The half-life period of SI
      EPL-M-TiO2 under continuous reaction was 114 h, and the conversion rate of
      sucrose after 16 batches consistently remained at around 95%, which indicates
      that SI-EPL-M-TiO2 has good operational stability. Thus, SI-EPL-M-TiO2 can be
      used as a biocatalyst in food industries.

PMID- 25977015
TI  - Harvest date affects aronia juice polyphenols, sugars, and antioxidant activity,
      but not anthocyanin stability.
AB  - The goal of this work was to characterize how the date of harvest of 'Viking'
      aronia berry impacts juice pigmentation, sugars, and antioxidant activity. Aronia
      juice anthocyanins doubled at the fifth week of the harvest, and then decreased.
      Juice hydroxycinnamic acids decreased 33% from the first week, while
      proanthocyanidins increased 64%. Juice fructose and glucose plateaued at the
      fourth week, but sorbitol increased 40% to the seventh harvest week. Aronia juice
      pigment density increased due to anthocyanin concentration, and polyphenol
      copigmentation did not significantly affect juice pigmentation. Anthocyanin
      stability at pH 4.5 was similar between weeks. However, addition of quercetin,
      sorbitol, and chlorogenic acid to aronia anthocyanins inhibited pH-induced loss
      of color. Sorbitol and citric acid may be partially responsible for weekly
      variation in antioxidant activity, as addition of these agents inhibited DPPH
      scavenging 13-30%. Thus, aronia polyphenol and non-polyphenol components
      contribute to its colorant and antioxidant functionality. 

PMID- 25977016
TI  - Identification of olive oil sensory defects by multivariate analysis of mid
      infrared spectra.
AB  - Mid-infrared (MIR) spectra (4000-600 cm(-1)) of olive oils were analyzed using
      chemometric methods to identify the four main sensorial defects, musty, winey,
      fusty and rancid, previously evaluated by an expert sensory panel. Classification
      models were developed using partial least squares discriminant analysis (PLS-DA)
      to distinguish between extra-virgin olive oils (defect absent) and lower quality
      olive oils (defect present). The most important spectral ranges responsible for
      the discrimination were identified. PLS-DA models were able to discriminate
      between defective and high quality oils with predictive abilities around 87% for
      the musty defect and around 77% for winey, fusty and rancid defects. This
      methodology advances instrumental determination of results previously only
      achievable with a human test panel.

PMID- 25977017
TI  - Fungi and the natural occurrence of deoxynivalenol and fumonisins in malting
      barley (Hordeum vulgare L.).
AB  - The industrial use of barley grain has experienced continuous growth, mainly due
      to its economic importance for malt production. From a technological perspective,
      fungal persistence can reduce product marketability and cause economic losses. In
      this sense, the aim of the present study was to determine the presence and
      identification of mycoflora and the occurrence of deoxynivalenol (DON) and
      fumonisins (FBs) in malting barley. The samples presented a low count of fungal
      colonies, with values ranging from 10.5 to 0.5 * 10(1)CFU g(-1) and the species
      most found were Fusarium graminearum and Fusarium verticillioides with 26% and
      12% of incidence, respectively. In the samples analyzed for mycotoxins
      occurrence, DON and FBs were present in 18% and 12%, respectively. The high
      concentrations of toxins found in the malting samples may be strongly influenced
      by agricultural practices and the weather conditions during critical phases of
      plant growth.

PMID- 25977018
TI  - 6-Benzylaminopurine inhibits growth of Monilinia fructicola and induces defense
      related mechanism in peach fruit.
AB  - This study demonstrated the inhibitory effect of 6-benzylaminopurine (BAP), the
      first generation synthetic cytokinin, on the invasion of Monilinia fructicola in
      peach fruit and the possible mechanism involved for the first time. Our results
      suggested that BAP treatment had a 63% lower disease incidence and approximately
      10 times lower lesion diameter compared to the control throughout the incubation
      period. In vitro BAP showed a direct inhibitory effect on M. fructicola spore
      germination. BAP could prevent fruit texture deterioration and protect the cell
      membrane from oxidative stress, while no adverse effects were observed on fruit
      quality maintenance. Analysis of defense-related enzymes activities indicated
      that the use of BAP induced higher specific polyphenol oxidase and peroxidase
      activities which triggered stronger host defensive responses. Thus, our results
      verified the proposed mechanism of BAP in controlling M. fructicola by direct
      inhibitory effect, delay peach senescence and activation of defensive enzymes. 

PMID- 25977019
TI  - Effect of debranching and heat-moisture treatments on structural characteristics
      and digestibility of sweet potato starch.
AB  - The effects of debranching treatment (DT) and debranching-heat-moisture treatment
      (D-HMT) on the structural characteristics and in vitro digestibility of sweet
      potato starch were investigated. The results indicated that DT and D-HMT
      decreased the percentage of starch fraction with degree of polymerization (DP) ?
      13, increased the percentages of the other fractions, and decreased the molecular
      weight of starch sample. The D-HMT starch showed a considerable SDS content of
      31.60%. Compared with the DT starch sample, the T(o), T(p), T(c), T(c)-T(o) and
      DeltaH of D-HMT starch samples for the second endothermal were increased
      significantly, crystalline pattern was altered from C(a) to A type, the surface
      became more smooth. The pasting temperatures of DT and D-HMT starch samples were
      higher while the peak viscosities, breakdown and setback values were lower than
      that of native starch. These results suggested that structural changes of sweet
      potato starch by D-HMT significantly affected the digestibility.

PMID- 25977020
TI  - Enzymatic synthesis of triacylglycerols of docosahexaenoic acid:
      Transesterification of its ethyl esters with glycerol.
AB  - The synthesis of docosahexaenoyl triacylglycerides at low temperature (e.g., 50
      degrees C) using biocatalysts of 6 commercial lipases adsorbed on hydrophobic
      supports was studied. In general, the triacylglyceride yields were very low with
      the exceptions of those produced with the enzymes from Candida antarctica
      fraction B, CALB (82%), and those produced with the enzyme from Pseudomonas
      fluorescens, PFL (57%). The reactions were performed under vacuum to remove the
      released ethanol. The yields varied widely when different derivatives of CALB
      were used, and they were higher when CALB adsorbed on hydrophobic supports was
      used (82%). One interesting by-product (18% of sn-2 monoacylglyceride of DHA)
      remained at the end of the synthetic process. CALB adsorbed on Sepabeads
      exhibited better activity and stability than did the commercial derivative
      Novozym 435. The best CALB biocatalyst preserved 90% of the activity after 30days
      under the reaction conditions. 

PMID- 25977021
TI  - Evidence of peptide oxidation from major myofibrillar proteins in dry-cured ham.
AB  - In this study, a peptidomic approach has been used in the identification of
      naturally generated peptides during a dry-curing process, showing methionine
      (Met) oxidation in their sequence. A total of 656 peptides derived from major
      myofibrillar proteins in Protected Designation of Origin (PDO) Teruel dry-cured
      ham have been identified by nanoliquid chromatography coupled to tandem mass
      spectrometry (nLC-MS/MS), including 120 peptides showing methionine oxidation.
      The percentage of oxidised peptides in the studied proteins ranged from 6% to
      35%, being peptides derived from nebulin, titin, myosin heavy chains, and
      troponin I proteins, those showing the highest number of oxidised methionine. The
      identification of the peptide sequence incorporating the oxidised amino acid
      provides valuable information of neighbouring amino acids, degree of hydrolysis
      of the sample, and characteristics of the peptide, which might be very useful for
      a future better understanding of the oxidation mechanisms occurring in dry-curing
      processing. 

PMID- 25977022
TI  - Changes in 4-vinylsyringol and other phenolics during rapeseed oil refining.
AB  - The aim of the present study was to examine changes in phenolic compounds during
      refining of rapeseed oil. In crude rapeseed oil, 4-vinylsyringol (canolol) is the
      dominant phenolic compound, accounting for 85% of total phenolics. Refining
      decreased the total amount of phenolic compounds by 90%. NMR and MS analyses of
      edible rapeseed oil phenolic extracts identified 4-vinylsyringol dimer as the
      dominant phenolic compound. This phenolic compound appears to form through acid
      catalyzed dimerization-aromatic substitution of 4-vinylsyringol monomers.
      Analysis of rapeseed oils from different stages of the refining process suggest
      that 4-vinylsyringol dimer forms during the neutralization phase, when H3PO4 acts
      as a catalyst, or during bleaching, when acid-activated bleaching earth acts as
      the catalyst. Whether 4-vinylsyringol forms during one or the other phase appears
      to depend on the phospholipid content of the crude oil. These insights may be
      useful for designing rapeseed oil refining processes that maximize levels of 4
      vinylsyringol dimer. 

PMID- 25977024
TI  - Chlorophylls and carotenoids of kiwifruit puree are affected similarly or less by
      microwave than by conventional heat processing and storage.
AB  - The impact of microwave (1000 W - 340 s) and conventional heat (97  degrees C -
      30s) pasteurisation and storage (4, 10, 22  degrees C for up to 63 d) on total
      and individual carotenoids and chlorophylls in kiwifruit puree was evaluated.
      Bioaccessibility of carotenoids, before and after pasteurisation and storage, was
      also studied. Microwaves and conventional heating led to marked changes in the
      chlorophyll (42-100% losses) and carotenoid (62-91% losses) content. First- and
      second-order kinetics appropriately explained the degradation of total
      carotenoids and chlorophylls over time, respectively. Pasteurised samples showed
      significantly (p < 0.05) enhanced stability of these pigments, with microwaves (k
      = 0.007-0.031100 g mg(-1) day(-1) at 4-22  degrees C) promoting chlorophyll
      stability to a greater extent than conventional heating (k = 0.0015-0.034100 g
      mg(-1) day(-1) at 4-22  degrees C). Bioaccessibility of carotenoids remained (p <
      0.05) unaffected by processing and storage. These results highlighted that the
      pigment composition of microwaved kiwifruit was more similar to that of the fresh
      fruit and better preserved during storage.

PMID- 25977023
TI  - Changes in analytical and volatile compositions of red wines induced by pre
      fermentation heat treatment of grapes.
AB  - Experiments were carried out on Grenache, Carignan and Fer grapes in order to
      characterize the changes in nitrogen content of the musts, conventional
      enological parameters and aroma compounds of the wines induced by pre
      fermentation heating of the grapes followed by alcoholic fermentation in liquid
      phase or in solid phase. In comparison to a standard vinification, we showed that
      a two-hour heat treatment at 70  degrees C induced a significant loss in several
      grape-derived aroma compounds (terpenols, norisoprenoids and some phenols)
      associated with an increase in alpha-terpineol, guaiacol and 2,6-dimethoxyphenol,
      which suggests thermal degradation. A significant increase in most of the ethyl
      esters, in acetates and in fatty acids were observed in wines fermented in liquid
      phase, together with a decrease in fusel alcohols. The substantial modification
      in the amino acid composition of the must seems to be a crucial element for the
      understanding of these changes.

PMID- 25977025
TI  - Effect of thermal treatment on secondary structure and conformational change of
      mushroom polyphenol oxidase (PPO) as food quality related enzyme: A FTIR study.
AB  - In order to understand the conformational changes of polyphenol oxidase (PPO),
      which is a food quality related enzyme, after thermal treatment, secondary
      structure changes of the enzyme were analyzed by using Fourier Transform Infrared
      (FTIR) spectroscopy and compared with the change in enzyme activity in the
      temperature range of 25-80  degrees C. Fourier self-deconvolution, neural network
      (NN) and curve-fitting analysis were applied to the amide I band of FTIR spectra
      for detail analysis of secondary structure elements. FTIR analysis indicated that
      PPO is an alpha-helix dominating enzyme. Detail analysis revealed that, as
      temperature increased, alpha-helix and beta-sheet decreased, but aggregated beta
      sheet, turns and random coil increased. The marked changes were noted at 40 
      degrees C with the occurrence of new bands due to aggregated beta-sheet
      structures, all of which indicate protein denaturation. These aggregation bands
      were still observed when the temperature was reduced back to 25  degrees C, from
      70  degrees C, demonstrating an irreversible change in the structure.

PMID- 25977026
TI  - Antioxidant peptides from corn gluten meal: Orthogonal design evaluation.
AB  - Protamex catalyzed corn gluten meal (CGM) hydrolysis peptides (CHP) were
      prepared. Orthogonal design L16 (4(5)) was used to optimize processing variables
      of CGM concentration, CGM heat pretreatment (121  degrees C) time, and
      enzymolysis pH, temperature, and time. Degree of hydrolysis (DH), undigested
      residue ratio, molecular weight (MW) distribution and DPPH radical inhibition
      were selected as analysis indicators. Optimum variables were CGM concentration of
      18%, heat pretreatment time of 40 min, and enzymolysis pH, temperature and time
      of 7.5, 55  degrees C and 24h, respectively. Verification test showed that CHP
      IC50 for scavenging hydroxyl radical was the best and then followed by reducing
      power. Oligopeptides improved after hydrolysis at the expense of di- and
      tripeptides, suggesting formation of soluble aggregates from low MW peptides. The
      increase in the DH, oligopeptides, Alanyl-Tyrosine, and antioxidant free amino
      acids coincided with the improvement in the antioxidant activity of CHP.

PMID- 25977027
TI  - Letter to the editor.

PMID- 25977028
TI  - Wheat milling by-products and their impact on bread making.
AB  - This study investigates the relationship between the properties of dietary fiber
      (DF) rich wheat milling by-products and their impact on bread making. From coarse
      bran over coarse and fine weatings to low grade flour, the content of starch and
      lipids increased, while that of DF and ash decreased. Enzyme activity levels
      differed strongly and were not related to other by-product properties. Average
      particle size of the by-products was positively correlated with DF and ash
      contents and their hydration properties. When meals from flour and by-products
      were composed on the same overall starch level to compensate for differences in
      endosperm contamination in the by-products, bread specific volume was more
      strongly depressed with fine weatings and low grade flour than with coarse bran
      and weatings. This suggests that the properties of the former were intrinsically
      more detrimental to bread making than those of the latter. 

PMID- 25977029
TI  - Extraction and characterisation of pomace pectin from gold kiwifruit (Actinidia
      chinensis).
AB  - Gold kiwifruit pomace extracted using citric acid, water and enzyme (Celluclast
      1.5L) were studied in terms of pectin yield, protein, ash, non-starch
      polysaccharide, galacturonic acid (GalA), neutral sugar composition, molar mass
      (Mw), viscosity and degree of branching. Water-extracted pectin was considered
      closest to its native form. Enzyme extracted pectin showed the highest yield (~
      4.5%w/w) as compared with the acid and water extraction methods (~ 3.6-3.8%w/w).
      Pectin obtained from different extraction methods showed different degree of
      branching. The Mw and root mean square (RMS) radius varied with the extraction
      methods with values of 8.4 * 10(5) g/mol and 92 nm, 8.5 * 10(5)g/mol and 102 nm,
      6.7 * 10(5) g/mol and 52 nm for acid, water and enzymatic extraction methods,
      respectively. Similar trend was observed for pectin viscosity, with water
      extracted pectin giving a slightly higher viscosity followed by acid and enzyme
      extracted pectin. This study showed that gold kiwifruit pomace pectin has
      potential application in food products.

PMID- 25977030
TI  - Authentication of processed meat products by peptidomic analysis using rapid
      ambient mass spectrometry.
AB  - We present the application of a novel ambient LESA-MS method for the
      authentication of processed meat products. A set of 25 species and protein
      specific heat stable peptide markers has been detected in processed samples
      manufactured from beef, pork, horse, chicken and turkey meat. We demonstrate that
      several peptides derived from myofibrillar and sarcoplasmic proteins are
      sufficiently resistant to processing to serve as specific markers of processed
      products. The LESA-MS technique required minimal sample preparation without
      fractionation and enabled the unambiguous and simultaneous identification of
      skeletal muscle proteins and peptides as well as other components of animal
      origin, including the milk protein such as casein alpha-S1, in whole meat product
      digests. We have identified, for the first time, six fast type II and five
      slow/cardiac type I MHC peptide markers in various processed meat products. The
      study demonstrates that complex mixtures of processed proteins/peptides can be
      examined effectively using this approach. 

PMID- 25977031
TI  - Identification by FT-ICR-MS of Camelus dromedarius alpha-lactalbumin variants as
      the result of nonenzymatic deamidation of Asn-16 and Asn-45.
AB  - Nonenzymatic deamidation of asparaginyl residues can occur spontaneously under
      physiological conditions principally when a glycyl residue is at the carboxyl
      side of Asn and leads to formation of aspartyl and isoaspartyl residues. This
      modification can change the biological activity of proteins or peptides and
      trigger an auto-immune response. The alpha-lactalbumins of members of the
      Camelidae family are the only of described alpha-lactalbumins that carry two
      AsnGly sequences. In the present study, high-resolution mass spectrometry, which
      enables accurate mass measurement has shown that Asn(16) and Asn(45) underwent a
      nonenzymatic deamidation, the sequence Asn(45)-Gly(46) being deamidated
      spontaneously at near-neutral and basic pH and Asn(16)-Gly(17) rather at basic
      pH. The 16-17 sequence was probably stabilized at near-neutral pH by hydrogen
      bonds according to the molecular modelisation performed with the camel protein. 

PMID- 25977032
TI  - Does Lactobacillus plantarum or ultrafiltration process improve Ca, Mg, Zn and P
      bioavailability from fermented goats' milk?
AB  - Ca, Mg, Zn and P bioavailability from two experimental ultrafiltered fermented
      goats' milks (one of them with the probiotic Lactobacillus plantarum and another
      one without it), and fermented goats' milk samples available in the market were
      evaluated. Solubility, dialysability and a model combining simulated
      gastrointestinal digestion and mineral retention, transport and uptake by Caco-2
      cells were used to assess bioavailability. The highest Ca, Mg, Zn and P
      bioavailability values always corresponded to the fermented milk developed by our
      research group, which could be explained by the effect of milk ultrafiltration.
      The fermented milk with L. plantarum showed higher Ca retention than the ones
      without the microorganism, and major Ca uptake when compared to commercial
      products. This fact could be attributed to a positive effect exerted by the
      probiotic strain. 

PMID- 25977033
TI  - Effects of enzymatic hydrolysis on conformational and functional properties of
      chickpea protein isolate.
AB  - The impact of enzymatic hydrolysis by Alcalase on the conformational and
      functional properties of chickpea protein isolate (CPI) was investigated. The
      physicochemical, interfacial tension and surface characteristics of CPI and their
      hydrolysates (CPH) according to the degree of hydrolysis (DH) were also
      determined. These parameters were then related to the changes in the
      emulsification activity (EAI) and stability (ESI). The enzymatic hydrolysis was
      found to improve protein recovery and solubility, leading to a reduction in the
      molecular weight bands with a concomitant increase in the intensity and
      appearance of protein bands having apparent molecular mass below 20 kDa. The
      interfacial tension decreased from ~ 66.5 mN m(-1) for CPI to ~ 59.1 m Nm(-1) for
      CPH. A similar trend was observed for the surface charge which declined from 
      27.55 mV to -16.4 mV for the CPI and CPH, respectively. These changes were found
      to have a detrimental effect on the EAI and ESI values.

PMID- 25977034
TI  - Novel restricted access materials combined to molecularly imprinted polymers for
      selective solid-phase extraction of organophosphorus pesticides from honey.
AB  - A novel restricted access materials (RAM) combined to molecularly imprinted
      polymers (MIPs), using malathion as template molecule and glycidilmethacrylate
      (GMA) as pro-hydrophilic co-monomer, were prepared for the first time. RAM-MIPs
      with hydrophilic external layer were characterized by scanning electron
      microscopy and recognition and selectivity properties were compared with the
      restricted access materials-non-molecularly imprinted polymers (RAM-NIPs) and
      unmodified MIPs. RAM-MIPs were used as the adsorbent enclosed in solid phase
      extraction column and several important extraction parameters were
      comprehensively optimized to evaluate the extraction performance. Under the
      optimum extraction conditions, RAM-MIPs exhibited comparable or even higher
      selectivity with greater extraction capacity toward six kinds of organophosphorus
      pesticides (including malathion, ethoprophos, phorate, terbufos, dimethoate, and
      fenamiphos) compared with the MIPs and commercial solid phase extraction columns.
      The RAM-MIPs solid phase extraction coupled with gas chromatography was
      successfully applied to simultaneously determine six kinds of organophosphorus
      pesticides from honey sample. The new established method showed good linearity in
      the range of 0.01-1.0 MUg mL(-1), low limits of detection (0.0005-0.0019 MUg mL(
      1)), acceptable reproducibility (RSD, 2.26-4.81%, n = 6), and satisfactory
      relative recoveries (90.9-97.6%). It was demonstrated that RAM-MIPs solid phase
      extraction with excellent selectivity and restricted access function was a
      simple, rapid, selective, and effective sample pretreatment method.

PMID- 25977035
TI  - Characterization of total antioxidant capacity and (poly)phenolic compounds of
      differently pigmented rice varieties and their changes during domestic cooking.
AB  - In the recent years, the pigmented rice varieties are becoming more popular due
      to their antioxidant properties and phenolic content. In this study, we
      characterized the antioxidant capacity (TAC) and the phenolic profile in white,
      red and black rice varieties, and evaluated the effect of two cooking methods
      (i.e. "risotto" and boiling) on these compounds. Before the cooking, all the
      varieties contained several phenolic acids, whereas anthocyanins and flavonols
      were peculiar of black rice and flavan-3-ols of red rice. Among the rice
      varieties, the black had the highest TAC value. The content of (poly)phenolic
      compounds and TAC decreased after cooking in all three varieties, but to a lesser
      extent after the risotto method. As a consequence, the risotto cooking, which
      allows a complete absorption of water, would be a good cooking method to retain
      (poly)phenolic compounds and TAC in pigmented and non-pigmented whole-meal rice. 

PMID- 25977036
TI  - Structure and digestibility of debranched and repeatedly crystallized waxy rice
      starch.
AB  - Debranched waxy rice starch was subjected to repeated crystallization (RC)
      treatment, and its physicochemical properties and digestion pattern were
      investigated. The A-type crystalline pattern of native starch was crystallized to
      a complex of B- and V-type patterns by debranching and RC treatment. Among the
      treated starches, the relative crystallinity of debranched starch reached its
      maximum (29.6%) after eight repetitions of crystallization. Changes in weight
      average molar mass among treated starch samples were not significantly different.
      The repeated-crystallized starches showed higher thermal transition temperatures
      and melting enthalpy than that of debranched starch. As a result, slowly
      digestible starch (SDS) content of repeated-crystallized starches reached a very
      high level (57.8%). Results showed that RC treatment induced structural changes
      of waxy rice starch result in a great amount of SDS. 

PMID- 25977037
TI  - Effect of high pressure--low temperature treatments on structural characteristics
      of whey proteins and micellar caseins.
AB  - In this study, structural changes in micellar caseins and whey proteins due to
      high pressure--low temperature treatments (HPLT) were investigated and compared
      to changes caused by high pressure treatments at room temperature. Whey protein
      isolate (WPI) solutions as well as micellar casein (MC) dispersions and mixtures
      were treated at 500 MPa (pH 7.0 and 5.8) at room temperature, -15  degrees C and 
      35  degrees C. Surface hydrophobicity and accessible thiol groups remained nearly
      unchanged after HPLT treatments whereas HP treatments at room temperature caused
      an unfolding of the WPI, resulting in an increase in surface hydrophobicity and
      exposure of the thiol groups. For HPLT treatments, distinct changes in the
      secondary structure (increase in the amount of beta-sheets) were observed while
      the tertiary structure remained unchanged. Large flocs, stabilized by hydrophobic
      interactions and hydrogen bonds, were formed in casein containing samples due to
      HPLT treatments. Depending on the pH and the applied HPLT treatment parameters,
      these interactions differed significantly from the interactions determined in
      native micelles.

PMID- 25977038
TI  - Antioxidants in heat-processed koji and the production mechanisms.
AB  - We previously developed antioxidative heat-processed (HP)-koji via two-step
      heating (55  degrees C/2days -> 75  degrees C/3 days) of white-koji. In this
      study, we isolated antioxidants in HP-koji and investigated their formation
      mechanisms. The antioxidants were identified to be 5-hydroxymethyl furfural (HMF)
      and 5-(alpha-D-glucopyranosyloxymethyl)-2-furfural (GMF) based on nuclear
      magnetic resonance spectral analysis. HMF and GMF were not present in intact
      koji, but were formed by heating at 75  degrees C. As production of these
      antioxidants was more effective by two-step heating than by constant heating at
      55  degrees C or 75  degrees C, we presumed that the antioxidant precursors are
      derived enzymatically at 55 degrees C and that the antioxidants are formed
      subsequently by thermal reaction at 75  degrees C. The heating assay of
      saccharide solutions revealed glucose and isomaltose as HMF and GMF precursors,
      respectively, and thus the novel finding of GMF formation from isomaltose.
      Finally, HMF and GMF were effectively formed by two-step heating from glucose and
      isomaltose present in koji.

PMID- 25977039
TI  - In vitro antibacterial activities and mechanism of sugar fatty acid esters
      against five food-related bacteria.
AB  - The objective of this study was to evaluate the antibacterial activities of sugar
      fatty acid esters, with different fatty acid and saccharide moieties, against
      five food-related bacteria including Bacillus cereus, Bacillus subtilis,
      Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. Sucrose
      monocaprate showed the strongest antibacterial activity against all tested
      bacteria, especially Gram-positive bacteria. The minimum inhibitory
      concentrations (MICs) for Gram-positive bacteria and Gram-negative bacteria were
      2.5 and 10 mM, respectively. The minimum bactericidal concentrations (MBCs) for
      Gram-positive bacteria were 10 mM. Time-kill assay also showed that sucrose
      monocaprate significantly inhibit the growth of tested bacteria. The permeability
      of the cell membrane and intracellular proteins were both changed by sucrose
      monocaprate according to cell constituents' leakage, SDS-PAGE and scanning
      electron microscope assays. It is suggested that sucrose monocaprate, with both
      emulsifying and antibacterial activities, have a potential to serve as a safe
      multifunctional food additive in food industries.

PMID- 25977040
TI  - Effects of citric acid esterification on digestibility, structural and
      physicochemical properties of cassava starch.
AB  - In this study, citric acid was used to react with cassava starch in order to
      compare the digestibility, structural and physicochemical properties of citrate
      starch samples. The results indicated that citric acid esterification treatment
      significantly increased the content of resistant starch (RS) in starch samples.
      The swelling power and solubility of citrate starch samples were lower than those
      of native starch. Compared with native starch, a new peak at 1724 cm(-1) was
      appeared in all citrate starch samples, and crystalline peaks of all starch
      citrates became much smaller or even disappeared. Differential scanning
      calorimetry results indicated that the endothermic peak of citrate starches
      gradually shrank or even disappeared. Moreover, the citrate starch gels exhibited
      better freeze-thaw stability. These results suggested that citric acid
      esterification induced structural changes in cassava starch significantly
      affected its digestibility and it could be a potential method for the preparation
      of RS with thermal stability.

PMID- 25977041
TI  - New monoterpene glycosides from sunflower seeds and their protective effects
      against H2O2-induced myocardial cell injury.
AB  - Three new monoterpene glycosides (1-3) and eleven known compounds (4-14) were
      isolated from seeds of Helianthus annuus L. (sunflower). Their structures were
      determined by spectroscopic and chemical methods. All the compounds were isolated
      from sunflower seeds for the first time. Protective effects of compounds 1-14
      against H2O2-induced H9c2 cardiomyocyte injury were evaluated, and compounds 1
      and 2 showed some cell-protective effects. No significant DPPH radical scavenging
      activity was observed for compounds 1-14. 

PMID- 25977042
TI  - Rapid method for the determination of 14 isoflavones in food using UHPLC coupled
      to photo diode array detection.
AB  - A rapid method for the determination of 14 types of isoflavones in food using
      ultra-high performance liquid chromatography (UHPLC) was validated in terms of
      precision, accuracy, sensitivity and linearity. The UHPLC separation was
      performed on a reverse-phase C18 column (particle size 2 MUm, i.d. 2 mm, length
      100 mm) using a photo diode array detector that was fixed to 260 nm. The limits
      of detection and quantification of the UHPLC analyses ranged from 0.03 to 0.33 mg
      kg(-1). The intra-day and inter-day precision of the individual isoflavones were
      less than 11.77% and calibration curves exhibited good linearity (r(2) = 0.99)
      within the tested ranges. These results suggest that the rapid method used in
      this study could be available to determine of 14 types of isoflavones in a
      variety of food such as soy bean, black bean, red bean and soybean paste.

PMID- 25977043
TI  - Consumer acceptance and stability of spray dried betanin in model juices.
AB  - Spray dried beetroot powder was used to colour model juices, and the consumer
      acceptance of the juices and stability of the colour during storage at 60 
      degrees C, 20  degrees C, 4  degrees C, and -20  degrees C were studied. The
      majority of the consumers preferred the model juices coloured with anthocyanins
      or beetroot extract over model juices coloured with spray dried beetroot powder.
      The consumers preferred more intensely coloured samples over lighter samples.
      Spray dried betanin samples were described as 'unnatural' and 'artificial'
      whereas the colour of beetroot extract was described more 'natural' and 'real
      juice'. No beetroot-derived off-odours or off-flavours were perceived in the
      model juices coloured with beetroot powder. Colour stability in model juices was
      greatly dependent on storage temperature with better stability at lower
      temperatures. Colour stability in the spray dried powder was very good at 20 
      degrees C. Betacyanins from beetroot could be a potential colourant for food
      products that are stored cold.

PMID- 25977044
TI  - Encapsulation of CO2 into amorphous and crystalline alpha-cyclodextrin powders
      and the characterization of the complexes formed.
AB  - Carbon dioxide complexation was undertaken into solid matrices of amorphous and
      crystalline alpha-cyclodextrin (alpha-CD) powders, under various pressures (0.4
      1.6 MPa) and time periods (4-96 h). The results show that the encapsulation
      capacity of crystalline alpha-CD was significantly lower than that of amorphous
      alpha-CD at low pressure and short time (0.4-0.8 MPa and 4-24 h), but was
      markedly enhanced with an increase of pressure and prolongation of encapsulation
      time. For each pressure level tested, the time required to reach a near
      equilibrium encapsulation capacity of the crystalline powder was around 48 h,
      which was much longer than that of the amorphous one, which only required about
      8h. The inclusion complex formation of both types of alpha-CD powders was
      confirmed by the appearance of a CO2 peak on the FTIR and NMR spectra. Moreover,
      inclusion complexes were also characterized by DSC, TGA, SEM and X-ray analyses.

PMID- 25977045
TI  - Near and mid infrared spectroscopy and multivariate data analysis in studies of
      oxidation of edible oils.
AB  - Infrared spectroscopic techniques and chemometric methods were used to study
      oxidation of olive, sunflower and rapeseed oils. Accelerated oxidative
      degradation of oils at 60 degrees C was monitored using peroxide values and FT
      MIR ATR and FT-NIR transmittance spectroscopy. Principal component analysis (PCA)
      facilitated visualization and interpretation of spectral changes occurring during
      oxidation. Multivariate curve resolution (MCR) method found three spectral
      components in the NIR and MIR spectral matrix, corresponding to the oxidation
      products, and saturated and unsaturated structures. Good quantitative relation
      was found between peroxide value and contribution of oxidation products evaluated
      using MCR--based on NIR (R(2) = 0.890), MIR (R(2) = 0.707) and combined NIR and
      MIR (R(2) = 0.747) data. Calibration models for prediction peroxide value
      established using partial least squares (PLS) regression were characterized for
      MIR (R(2) = 0.701, RPD = 1.7), NIR (R(2) = 0.970, RPD = 5.3), and combined NIR
      and MIR data (R(2) = 0.954, RPD = 3.1).

PMID- 25977046
TI  - Purification and identification of Se-containing antioxidative peptides from
      enzymatic hydrolysates of Se-enriched brown rice protein.
AB  - As a further study of Se-containing proteins (Se-Pro) derived from Se-enriched
      brown rice (Se-BR), this paper aimed to purify and identify Se-containing
      antioxidative peptides (Se-antioxi-Peps) from Se-Pro hydrolysates. The total Se
      content in Se-BR was 6.26MUg/g DW, and selenocystine, Se-methylselenocysteine,
      and selenomethionine were identified as the main organic Se species by high
      performance liquid chromatography-inductively coupled plasma mass spectrometry.
      Se-Pro was extracted and hydrolyzed by four types of proteases, and Alcalase was
      chosen as the optimum enzyme according to the degree of hydrolysis (DH). The
      hydrolysate with 17.08% DH possessing the highest DPPH radical scavenging
      activity was separated into five fractions (F1 to F5). Fractions F3 to F5, which
      had high antioxidative activities, were further separated. Sub-fractions F3-3, F4
      2, and F5-1 were chosen to evaluate antioxidative activities and analyze Se
      species. The Se-antioxi-Pep with the sequence SeMet-Pro-Ser was identified by
      electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry. 

PMID- 25977047
TI  - Potential impact of rising atmospheric CO2 on quality of grains in chickpea
      (Cicer arietinum L.).
AB  - Experiments were conducted in open-top chambers to assess the effect of
      atmospheric CO2 enrichment (E-CO2) on the quality of grains in chickpea (Cicer
      arietinum L.) crop. Physical attributes of the grains was not affected, but the
      hydration and swelling capacities of the flour increased. Increase in
      carbohydrates and reduction in protein made the grains more carbonaceous (higher
      C:N) under E-CO2. Among other mineral nutrients, K, Ca and Zn concentrations
      decreased, while P, Mg, Cu, Fe, Mn and B concentrations did not change. The pH,
      bulk density and cooking time of chickpea flour remained unaffected, although the
      water absorption capacity of flour increased and oil absorption reduced. Results
      suggest that E-CO2 could affect the grain quality adversely and nutritional
      imbalance in grains of chickpea might occur. 

PMID- 25977048
TI  - Modifying glycoalkaloid content in transgenic potato--Metabolome impacts.
AB  - Metabolite profiling has been used to assess the potential for unintended
      composition changes in potato (Solanum tuberosum L. cv. Desiree) tubers, which
      have been genetically modified (GM) to reduce glycoalkaloid content, via the
      independent down-regulation of three genes SGT1, SGT2 and SGT3 known to be
      involved in glycoalkaloid biosynthesis. Differences between the three groups of
      antisense lines and control lines were assessed using liquid chromatography-mass
      spectrometry (LC-MS) and gas chromatography (GC)-MS, and data analysed using
      principal component analysis and analysis of variance. Compared with the wild
      type (WT) control, LC-MS revealed not only the expected changes in specific
      glycoalkaloid levels in the GM lines, but also significant changes in several
      other metabolites, some of which were explicable in terms of known pathways.
      Analysis of polar and non-polar metabolites by GC-MS revealed other significant
      (unintended) differences between SGT lines and the WT, but also between the WT
      control and other control lines used. 

PMID- 25977049
TI  - Temperature model for process impact non-uniformity in genipin recovery by high
      pressure processing.
AB  - A model for the process impact temperature non-uniformity during high pressure
      processing (HPP) of genipap fruit purees was found during genipin recovery.
      Purees were subjected to HPP (130-530 MPa) under quasi-isobaric non-isothermal
      conditions (15 min; 0, 4.6 and 9.3mg pectinases/g fruit). Genipin and protein
      concentration was determined, and pH was measured. Polygalacturonase activity was
      quantified indirectly by protein content (mg/g fruit). First order kinetics
      described temperature changes (0-4 min). Polygalacturonase was activated at 130
      MPa, inactivated reversibly at 330 MPa and activated again at 530 MPa. Enzyme
      reaction rate constant (k) was placed in the 0-4 min model and temperature from 2
      to 15 min was described. Protein content and pH characterization in terms of
      decimal reduction time improved highly the 2-15 min model. Since temperature
      changes were modeled, more insight of its behavior in an HPP reactor was
      obtained, avoiding uniformity assumptions, making easier the industrial scale HPP
      implementation.

PMID- 25977050
TI  - Physico-chemical and metabolomic characterization of KAMUT(r) Khorasan and durum
      wheat fermented dough.
AB  - Investigations were made in order to evaluate the influence of the flour type,
      chemical acidification and fermentation on characteristics of doughs obtained
      with durum wheat and KAMUT(r) Khorasan flour. Doughs were observed immediately
      after mixing, 90 and 360 min of leavening at 30  degrees C. Fundamental rheology,
      yeasts heat production by isothermal microcalorimetry and the interaction between
      water and biopolymers by means of time domain nuclear magnetic resonance were
      evaluated. In addition aromatic metabolite development was followed by means of
      the combined application of gas-chromatography and electronic nose. KAMUT(r)
      Khorasan flour was found to be more suitable than durum wheat for the
      fermentation processes tested, especially at acidic conditions, as shown by the
      increase of the volume and the metabolic heat production by yeast. In acidified
      dough the pattern of volatile metabolites allowed a clear distinction between the
      types of dough. Moreover the water/starch proton pool was characterized by higher
      T2 values in the KAMUT(r) Khorasan samples.

PMID- 25977052
TI  - Tracing tree nut allergens in chocolate: A comparison of DNA extraction
      protocols.
AB  - The present work aimed at comparing different DNA extraction methods, from
      chocolate matrices, for the effective application in molecular techniques to
      detect tree nut allergens. For this study, DNA from almond or hazelnut model
      chocolates was extracted using seven selected protocols: the in-house methods of
      CTAB-PVP (cetyltrimethylammonium bromide-polyvinylpyrrolidone), Wizard with and
      without RNase, Wizard-PVP with and without RNase, and the Wizard Magnetic and
      Nucleospin kits. The extracts were assessed for their suitability for
      amplification by qualitative PCR and real-time PCR. From the evaluated protocols,
      Nucleospin presented the best results for almond and hazelnut amplification,
      achieving a limit of detection of 0.005% (w/w) with high PCR efficiency,
      linearity and range of amplification. These results highlight the importance of
      the DNA extraction protocol in the case of food allergens from complex matrices,
      such as chocolate, in which sensitivity is a key parameter. 

PMID- 25977051
TI  - Effect-directed analysis of cold-pressed hemp, flax and canola seed oils by
      planar chromatography linked with (bio)assays and mass spectrometry.
AB  - Cold-pressed hemp, flax and canola seed oils are healthy oils for human
      consumption as these are rich in polyunsaturated fatty acids and bioactive
      phytochemicals. However, bioactive information on the food intake side is mainly
      focused on target analysis. For more comprehensive information with regard to
      effects, single bioactive compounds present in the seed oil extracts were
      detected by effect-directed assays, like bioassays or an enzymatic assay,
      directly linked with chromatography and further characterized by mass
      spectrometry. This effect-directed analysis is a streamlined method for the
      analysis of bioactive compounds in the seed oil extracts. All effective compounds
      with regard to the five assays or bioassays applied were detected in the samples,
      meaning also bioactive breakdown products caused during oil processing, residues
      or contaminants, aside the naturally present bioactive phytochemicals. The
      investigated cold-pressed oils contained compounds that exert antioxidative,
      antimicrobial, acetylcholinesterase inhibitory and estrogenic activities. This
      effect-directed analysis can be recommended for bioactivity profiling of food to
      obtain profound effect-directed information on the food intake side. 

PMID- 25977053
TI  - Development and validation of an HPLC/DAD method for the determination of 13
      sulphonamides in eggs.
AB  - A simple, sensitive and selective multiresidue high-performance liquid
      chromatography with diode array detection method for determination of 13
      sulphonamides in eggs was developed and validated. Sample extraction and clean-up
      conditions were carefully studied and factors as gradient elution and column
      temperature were found as key parameters to improve separation efficiency. The
      method was validated following the European Commission Decision 2002/657/EC
      criteria adopting spiking levels of 20, 40 and 60 MUg kg(-1) "As Low As
      Reasonably Achievable". The necessary requirements for precision (RSDR% below
      23%) and trueness (recovery ranging from 45.2% to 87.5%) were fulfilled. Decision
      limit (CCalpha) values below 18.5 MUg kg(-1), comparable to those reported in LC
      MS detection, demonstrated the suitability of the method in residues surveillance
      plans for the sulphonamides analysis in eggs at the carry-over level without the
      use of sophisticated and expensive instrumentation.

PMID- 25977054
TI  - Thermal and pressure stability of myrosinase enzymes from black mustard (Brassica
      nigra L. W.D.J. Koch. var. nigra), brown mustard (Brassica juncea L. Czern. var.
      juncea) and yellow mustard (Sinapsis alba L. subsp. maire) seeds.
AB  - This study investigates the effects of temperature and pressure on inactivation
      of myrosinase extracted from black, brown and yellow mustard seeds. Brown mustard
      had higher myrosinase activity (2.75 un/mL) than black (1.50 un/mL) and yellow
      mustard (0.63 un/mL). The extent of enzyme inactivation increased with pressure
      (600-800 MPa) and temperature (30-70 degrees  C) for all the mustard seeds.
      However, at combinations of lower pressures (200-400 MPa) and high temperatures
      (60-80  degrees C), there was less inactivation. For example, application of 300
      MPa and 70  degrees C for 10 min retained 20%, 80% and 65% activity in yellow,
      black and brown mustard, respectively, whereas the corresponding activity
      retentions when applying only heat (70 degrees  C, 10 min) were 0%, 59% and 35%.
      Thus, application of moderate pressures (200-400 MPa) can potentially be used to
      retain myrosinase activity needed for subsequent glucosinolate hydrolysis.

PMID- 25977055
TI  - Pyrrolizidine alkaloids in herbal teas for infants, pregnant or lactating women.
AB  - A general contamination of tea with pyrrolizidine alkaloids (PA) has just become
      known. Here, we report the application and modification of a new HPLC-ESI-MS/MS
      sum parameter method to quantitate PA content of herbal teas intended for
      infants, pregnant and lactating women. Using p-toluenesulfonyl isocyanate for
      derivatization and a stable isotope labeled internal standard, the total
      retronecine-/heliotridine-type PA content of the samples is expressed in form of
      a single sum parameter (retronecine equivalents: RE). The new methods were
      applied to analyze 44 tea samples for such consumer groups. Thirty eight products
      (86%) were tested PA positive showing PA concentrations ranging from 0 to 391 MUg
      RE/kg (average: 50 MUg RE/kg). The dataset is discussed in the view of the
      current discussion on PA in the food chain with special focus on those particular
      vulnerable consumer groups.

PMID- 25977057
TI  - Comparison of microwave, ultrasound and accelerated-assisted solvent extraction
      for recovery of polyphenols from Citrus sinensis peels.
AB  - Peel of Citrus sinensis contains significant amounts of bioactive polyphenols
      that could be used as ingredients for a number of value-added products with
      health benefits. Extraction of polyphenols from the peels was performed using a
      microwave-assisted extraction (MAE) technique. The effects of aqueous acetone
      concentration, microwave power, extraction time and solvent-to-solid ratio on the
      total phenolic content (TPC), total antioxidant activity (TAA) (using DPPH and
      ORAC-values) and individual phenolic acids (IPA) were investigated using a
      response surface method. The TPC, TAA and IPA of peel extracts using MAE was
      compared with conventional, ultrasound-assisted and accelerated solvent
      extraction. The maximum predicted TPC under the optimal MAE conditions (51%
      acetone concentration in water (v/v), 500 W microwave power, 122 s extraction
      time and 25 mL g(-1) solvent to solid ratio), was 12.20 mg GAE g(-1) DW. The TPC
      and TAA in MAE extracts were higher than the other three extracts.

PMID- 25977056
TI  - Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil
      type on lipid digestion and vitamin D3 bioaccessibility.
AB  - The influence of carrier oil type on the bioaccessibility of vitamin D3
      encapsulated within oil-in-water nanoemulsions prepared using a natural
      surfactant (quillaja saponin) was studied using a simulated gastrointestinal
      tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid
      release during lipid digestion decreased in the following order: medium chain
      triglycerides (MCT) > corn oil ~ fish oil > orange oil > mineral oil. Conversely,
      the measured bioaccessibility of vitamin D3 decreased in the following order:
      corn oil ~ fish oil > orange oil > mineral oil > MCT. These results show that
      carrier oil type has a considerable impact on lipid digestion and vitamin
      bioaccessibility, which was attributed to differences in the release of
      bioactives from lipid droplets, and their solubilization in mixed micelles.
      Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were
      most effective at increasing vitamin bioaccessibility.

PMID- 25977058
TI  - Characterization of composition traits related to organoleptic and functional
      quality for the differentiation, selection and enhancement of local varieties of
      tomato from different cultivar groups.
AB  - Tomato (Solanum lycopersicum) local varieties are having an increasing demand. We
      characterized 69 local tomato accessions from eight cultivar groups for proximate
      composition traits, major sugars, acids and antioxidants. A large diversity was
      found, with differences among accessions of almost tenfold for lycopene.
      Significant differences were found among cultivar group means for most traits.
      The Cherry and Penjar groups generally presented higher dry matter, soluble
      solids content, titratable acidity, taste index, beta-carotene, ascorbic acid,
      total phenolics, and antioxidant activity that the other groups. Wide ranges of
      variation were found within each cultivar group. Positive correlations were found
      between proximate traits related to taste and antioxidants. The multivariate
      principal components analysis confirms the distinct profile of the Cherry and
      Penjar groups and the large variation within groups. The results will be useful
      for the differentiation, enhancement and selection of local tomato varieties with
      improved organoleptic properties and functional quality. 

PMID- 25977059
TI  - Evaluation of canola oil oleogels with candelilla wax as an alternative to
      shortening in baked goods.
AB  - The oleogels of canola oil with candelilla wax were prepared and utilized as a
      shortening replacer to produce cookies with a high level of unsaturated fatty
      acids. The incorporation of candelilla wax (3% and 6% by weight) to canola oil
      produced the oleogels with solid-like properties. The firmness of the oleogels
      was lower than that of the shortening at room temperature. A more rapid change in
      the viscosity with temperature was observed with increasing levels of candelilla
      wax in the steady shear measurements. The replacement of shortening with oleogels
      in the cookie formulation reduced both viscoelastic parameters (G' and G") of the
      cookie doughs. The level of unsaturated fatty acids in the oleogel cookies was
      distinctly increased up to around 92%, compared to the shortening cookies
      (47.2%). The cookies with the oleogels showed desirable spreadable property and
      the replacement of shortening with the oleogels produced cookies with soft eating
      characteristics.

PMID- 25977060
TI  - Monoclonal antibody-based immunoassays for cyprodinil residue analysis in
      QuEChERS-based fruit extracts.
AB  - Cyprodinil is among the most common agrochemical residues found in highly
      perishable fruits, such as strawberries. In the present study, high-affinity
      monoclonal antibodies to this anilinopyrimidine fungicide were raised for the
      first time with the aim to produce valuable immunochemical analytical assays.
      Cyprodinil bioconjugates and the generated novel monoclonal antibodies were
      employed for sensitive competitive immunoassay development in two different
      formats. The limits of detection of the optimized assays were 20 and 30 ng L(-1)
      for the indirect and direct assay, respectively. Influence over assay parameters
      of different physicochemical factors was studied. Strawberry samples were
      extracted following the recommended QuEChERS procedure for pesticide residues in
      food, and analyzed by the optimized immunoassays. Recoveries and coefficients of
      variation from fortified samples were within standard values. In addition, the
      obtained immunochemical results with naturally contaminated samples were
      statistically comparable, according to Deming regression analysis, to those of a
      reference chromatographic method.

PMID- 25977061
TI  - Predicting anthocyanins' isothermal and non-isothermal degradation with the
      endpoints method.
AB  - The thermal degradation of anthocyanins in a variety of media and over a large
      temperature range is known to follow first-order kinetics, and the temperature
      dependence of the exponential rate constant a two-parameter model. These
      parameters can be estimated from the initial and final concentrations of only two
      isothermal or non-isothermal heat treatments by numerically solving a pair of
      simultaneous equations of which they are the two unknowns. Once calculated they
      can be used to reconstruct the entire degradation curves and predict those of
      other heat treatments in a pertinent temperature range. Commercial mathematical
      software can do the calculations, as demonstrated with computer simulations and
      published data on the isothermal and non-isothermal degradation of anthocyanins.
      The endpoints method's predictions were confirmed by comparison to the reported
      experimentally determined final concentrations. Where applicable, the method will
      eliminate the need to record sets of whole isothermal degradation curves in
      studies of the kinetics of anthocyanins' degradation. 

PMID- 25977062
TI  - Influence of denaturation and aggregation of beta-lactoglobulin on its tryptic
      hydrolysis and the release of functional peptides.
AB  - Whereas previous studies showed that thermal pre-treatment of whey proteins
      promote their enzymatic hydrolysis, to date no correlation between the
      conformation of denatured protein and the release of individual peptides has been
      considered. Hence, in this study total denaturation of beta-lactoglobulin was
      performed at defined pH-values to enable the generation of different denatured
      particles. The denatured proteins were used as substrate for tryptic hydrolysis
      and the hydrolysis progress was characterised by the degree of hydrolysis (DH)
      and the release of functional peptides, detected using LC-ESI-TOF/MS.
      Denaturation and subsequent aggregation of beta-lactoglobulin, induced by thermal
      treatment at pH 5.1, altered the DH slightly, whereas the release of investigated
      peptides was significantly decreased. Contrary, denaturation at pH 6.8 and 8.0
      led to formation of non-native monomers and reduced the DH to 75%, but showed
      promoting as well as reducing effects on the release of peptides, depending on
      their location within the protein. 

PMID- 25977063
TI  - Fast determination of biogenic amines in beverages by a core-shell particle
      column.
AB  - A fast and reliable HPLC method for the determination of 11 biogenic amines in
      beverages has been performed. After pre-column derivatization with dansyl
      chloride a Kinetex C18 core-shell particle column (100 mm * 4.6 mm, 2.6 MUm
      particle size) has been employed and the biogenic amines were identified and
      quantified in a total run time of 13 min with ultraviolet (UV) or fluorescence
      detection (FLD). Chromatographic conditions such as column temperature (kept at
      50  degrees C), gradient elution and flow rate have been optimized and the method
      has been tested on red wine and fruit nectar. The proposed method is enhanced in
      terms of reduced analysis time and eluent consumption with respect of classical
      HPLC method as to be comparable to UHPLC methods. Green and cost-effective, this
      method can be used as a quality-control tool for routine quantitative analysis of
      biogenic amines in beverages for the average laboratory.

PMID- 25977065
TI  - Determination of volatile compounds by GC-IMS to assign the quality of virgin
      olive oil.
AB  - The characterisation of different olive oil categories (extra virgin, virgin and
      lampante) using Ion Mobility Spectrometry (IMS) was improved by replacing the
      multicapillary column (MCC) with a capillary column (CC). The data obtained with
      MCC-IMS and CC-IMS were evaluated, studying both the global and the specific
      information obtained after the analysis of the volatile fraction of olive oils. A
      better differentiation of the oil categories was obtained employing CC vs MCC,
      since the classification percentage obtained with the CC-IMS was 92% as opposed
      to 87% obtained with MCC-IMS; although in productivity analytical terms, MCC
      offer a faster analysis than GC. The specific information obtained was also used
      to build a database, with a view to facilitating the characterization of specific
      attributes of olive oils. A total of 26 volatile metabolites (aldehydes, ketones,
      alcohols and esters) were identified. Finally, as revealed by an ANOVA test, some
      volatiles differed markedly in content among the different categories of oil. The
      data obtained confirms the potential of IMS as a reliable analytical screening
      technique, which can be used to assign the correct category to an olive oil
      sample. 

PMID- 25977064
TI  - Lipid oxidation in minced beef meat with added Krebs cycle substrates to
      stabilise colour.
AB  - Krebs cycle substrates (KCS) can stabilise the colour of packaged meat by oxygen
      reduction. This study tested whether this reduction releases reactive oxygen
      species that may lead to lipid oxidation in minced meat under two different
      storage conditions. KCS combinations of succinate and glutamate increased
      peroxide forming potential (PFP, 1.18-1.32 mmol peroxides/kg mince) and
      thiobarbituric acid reactive substances (TBARS, 0.30-0.38 mg malondialdehyde
      (MDA) equivalents/kg mince) under low oxygen storage conditions. Both succinate
      and glutamate were metabolised. Moreover, under high oxygen (75%) storage
      conditions, KCS combinations of glutamate, citrate and malate increased PFP (from
      1.22 to 1.29 mmol peroxides/kg) and TBARS (from 0.37 to 0.40 mg MDA
      equivalents/kg mince). Only glutamate was metabolised. The KCS combinations that
      were added to stabilise colour were metabolised during storage, and acted as pro
      oxidants that promoted lipid oxidation in both high and low oxygen conditions.

PMID- 25977066
TI  - Atypical nuclear localization of CD133 plasma membrane glycoprotein in
      rhabdomyosarcoma cell lines.
AB  - CD133 (also known as prominin-1) is a cell surface glycoprotein that is widely
      used for the identification of stem cells. Furthermore, its glycosylated epitope,
      AC133, has recently been discussed as a marker of cancer stem cells in various
      human malignancies. During our recent experiments on rhabdomyosarcomas (RMS), we
      unexpectedly identified an atypical nuclear localization of CD133 in a relatively
      stable subset of cells in five RMS cell lines established in our laboratory. To
      the best of our knowledge, this atypical localization of CD133 has not yet been
      proven or analyzed in detail in cancer cells. In the present study, we verified
      the nuclear localization of CD133 in RMS cells using three independent anti-CD133
      antibodies, including both rabbit polyclonal and mouse monoclonal antibodies.
      Indirect immunofluorescence and confocal microscopy followed by software cross
      section analysis, transmission electron microscopy and cell fractionation with
      immunoblotting were also employed, and all the results undeniably confirmed the
      presence of CD133 in the nuclei of stable minor subpopulations of all five RMS
      cell lines. The proportion of cells showing an exclusive nuclear localization of
      CD133 ranged from 3.4 to 7.5%, with only minor differences observed among the
      individual anti-CD133 antibodies. Although the role of CD133 in the cell nucleus
      remains unclear, these results clearly indicate that this atypical nuclear
      localization of CD133 in a minor subpopulation of cancer cells is a common
      phenomenon in RMS cell lines.

PMID- 25977067
TI  - Can be galectin-3 a novel marker in determining mortality in hemodialysis
      patients?
AB  - BACKGROUND: Cardiovascular (CV) mortality is common in hemodialysis (HD)
      patients. There are some difficulties involved in determining CV risk. Galectin-3
      is a molecule with a demonstrated correlation with CV mortality and which is
      approved in the stratification of heart failure (HF) risk. The purpose of this
      study was to assess the previously uninvestigated relationship between galectin-3
      and cardiac mortality in HD patients. METHODS: Two hundred ninety clinically
      stable HD patients aged over 18 and on a thrice-weekly intermittent HD program
      lasting >3 months and 30 healthy individuals were enrolled in this multi-center,
      prospective, observational study and monitored over 24 months. Blood specimens
      were collected at the start of the study for the measurement of galectin-3 and
      other biochemical parameters. At the end of the study, the relations between
      galectin-3 and other biochemical and demographic parameters and mortality were
      analyzed. RESULTS: Galectin-3 levels were significantly higher in the HD group
      compared to the control group (p < 0.001). All-cause mortality was observed in 63
      (21%) patients. At multivariate Cox regression analysis, age, low albumin, low
      DBP, high galectin-3 and high HsCRP were identified as prognostic determinants of
      all-cause mortality, while age, low albumin, high galectin-3 and high SBP were
      identified as prognostic determinants of cardiac mortality. CONCLUSION: This
      study shows, for the first time in the literature, that galectin-3 may be a novel
      biomarker of cardiac mortality in HD patients. We think that, when supported by
      further studies, galectin-3 can be a promising biomarker in predicting cardiac
      mortality in HD patients.

PMID- 25977068
TI  - Dynamic biological changes in metabolic disease biomarkers in childhood and
      adolescence: A CALIPER study of healthy community children.
AB  - BACKGROUND: Understanding age- and sex-specific biological changes in metabolic
      disease biomarkers is essential for their appropriate utilization in management
      of children with inborn errors of metabolism (IEM). The CALIPER program aimed to
      establish pediatric reference values in healthy community children for common
      metabolic biomarkers and determine the effects of key covariates including age
      and sex across the pediatric age. METHODS: A cohort of 500 healthy children and
      adolescents from birth to 19years were initially recruited to establish pediatric
      reference intervals according to the CLSI C28-A3 guidelines. Serum samples were
      used to measure 37 amino acids by ultra-performance liquid chromatography, 32
      acylcarnitines, as well as free and total carnitine by tandem mass spectrometry,
      and beta-hydroxybutyrate and free fatty acids using the Vitros 5.1 chemistry
      analyzer. P ediatric reference intervals were calculated using non-parametric
      statistics and partitioned based on age- and sex-distributions. RESULTS:
      Approximately 80% of all analytes required 2 to 4 age-dependent partitions, with
      over 50% of amino acids and over 70% of acylcarnitines exhibiting significant
      physiological changes during the neonatal period. Also, 21% of all analytes
      required partitioning during puberty and adolescence, half of which produced sex
      specific distributions. CONCLUSIONS: A comprehensive reference interval database
      for metabolic disease biomarkers established in this study will improve detection
      of IEMs by providing appropriate age- and sex-related information in the
      pediatric population. It will also aid newborn screening programs and guide the
      management of patients with known metabolic diseases, especially pubertal and
      adolescent boys and girls that display sex-specific concentrations.

PMID- 25977069
TI  - GlycA, a biomarker of inflammatory glycoproteins, is more closely related to the
      leptin/adiponectin ratio than to glucose tolerance status.
AB  - OBJECTIVES: Plasma GlycA is a recently developed biomarker whose nuclear magnetic
      resonance signal originates from glycosylated acute-phase proteins. The aim of
      our study was to determine potential relationships between GlycA and adiposity,
      insulin resistance (HOMA(ir)), high sensitive C-reactive protein (hs-CRP),
      leptin, adiponectin, and the leptin/adiponectin ratio, and to test whether GlycA
      is elevated in subjects with impaired fasting glucose (IFG) and type 2 diabetes
      mellitus (T2DM). DESIGN AND METHODS: Plasma GlycA, hs-CRP, leptin, adiponectin,
      the leptin/adiponectin ratio, and insulin resistance (HOMA(ir)) were measured in
      103 fasting subjects (30 with normal fasting glucose, 25 with IFG and 48 with
      T2DM). RESULTS: In all subjects combined, plasma GlycA was correlated positively
      with body mass index (BMI), HOMA(ir), hs-CRP, leptin and the leptin/adiponectin
      ratio, and inversely with adiponectin (p < 0.05 to p < 0.001). GlycA did not
      significantly vary according to glucose tolerance category (p = 0.060). GlycA was
      related positively to the leptin/adiponectin ratio (p = 0.049), independent of
      BMI (p = 0.056) and HOMA(ir) (p = 0.50). CONCLUSIONS: High plasma GlycA reflects
      a pro-inflammatory state. Adipose tissue-associated inflammatory processes could
      contribute to increased circulating levels of glycosylated acute-phase proteins.

PMID- 25977070
TI  - Effect of renal function on serum cardiac troponin T--Population and individual
      effects.
AB  - BACKGROUND: Elevations of serum cardiac troponin T (cTnT) have been described in
      patients with end stage chronic kidney disease (CKD) although the mechanism is
      unknown, whether from increased production or decreased clearance. Less is known
      about cTnT in short term changes in renal function and in lesser degrees of renal
      impairment. OBJECTIVES: This study aimed to investigate the effect of renal
      function changes on cTnT within individuals and characterise the distribution of
      cTnT according to renal function in the population. DESIGN AND METHODS: A
      hospital laboratory database extract was performed for paired creatinine and cTnT
      results. cTnT was compared with estimated glomerular filtration rate (eGFR) at
      the population level. In individuals who had undergone repeat testing, changes in
      cTnT were compared with corresponding changes in creatinine. RESULTS: At the
      population level, 17,113 cTnT and creatinine measurements from 10,418 patients
      demonstrated rising cTnT with falling eGFR, with no eGFR threshold for this
      effect. Of these, 3108 pairs of results were obtained from patients who had
      undergone repeat testing. The median retesting interval was 15 h (interquartile
      range: 7-25 h). Within individuals, the magnitude of changes in cTnT approximated
      33% of changes in creatinine. CONCLUSIONS: At the population level, moderate
      reductions in GFR (30-59 mL/min/1.73 m(2)) corresponded to a median cTnT above
      the 14 ng/L upper reference limit. The modest association between changes in cTnT
      and creatinine within individuals in the short term further highlights the need
      for caution when interpreting troponin elevations in this setting.

PMID- 25977071
TI  - Psychopathology associated with social withdrawal: Idiopathic and comorbid
      presentations.

PMID- 25977072
TI  - Alterations in plasma vascular endothelial growth factor levels in patients with
      schizophrenia before and after treatment.
AB  - Vascular endothelial growth factor (VEGF), a potent angiogenetic factor, is a
      known neurotrophic factor. In this study, we examined plasma levels of VEGF in 50
      patients with schizophrenia (SPR) and 50 healthy control subjects. We also
      explored any changes in plasma VEGF levels after 6-week treatment with
      antipsychotic agents in patients with schizophrenia. All subjects with
      schizophrenia were either medication-naive or medication-free for at least 4
      weeks before assessment. Plasma VEGF levels in all subjects were significantly
      correlated with smoking duration, which was considered to be a significant
      covariate. Pre-treatment plasma VEGF levels in patients with schizophrenia were
      significantly lower than those in healthy controls. Post-treatment VEGF levels
      were significantly increased in patients with schizophrenia. Plasma VEGF levels
      in patients with schizophrenia did not exhibit significant correlation with the
      total or subscale scores of the Positive and Negative Syndrome Scale (PANSS)
      either at baseline or at the end of the 6-week treatment. In conclusion, our
      findings reveal that plasma VEGF levels before treatment were lower in patients
      with schizophrenia and that their VEGF levels increased after treatment. Thus,
      VEGF may have a neuroprotective role in the improvement of schizophrenia or in
      the treatment effects of antipsychotics. 

PMID- 25977073
TI  - Therapist competence and therapeutic alliance are important in the treatment of
      health anxiety (hypochondriasis).
AB  - The role of treatment delivery factors (i.e., therapist adherence, therapist
      competence, and therapeutic alliance) is rarely investigated in psychotherapeutic
      treatment for health anxiety. This study aimed to investigate the role of the
      assessment perspective for the evaluation of treatment delivery factors and their
      relevance for treatment outcome. Therapist adherence, therapist competence, and
      therapeutic alliance were evaluated by independent raters, therapists, patients,
      and supervisors in 68 treatments. Patients with severe health anxiety
      (hypochondriasis) were treated with cognitive therapy or exposure therapy.
      Treatment outcome was assessed with a standardized interview by independent
      diagnosticians. A multitrait-multimethod analysis revealed a large effect for the
      assessment perspective of therapist adherence, therapist competence, and
      therapeutic alliance. The rater perspective was the most important for the
      prediction of treatment outcome. Therapeutic alliance and therapist competence
      accounted for 6% of the variance of treatment outcome while therapist adherence
      was not associated with treatment outcome. Therapist competence was only
      indirectly associated with treatment outcome, mediated by therapeutic alliance.
      Both therapeutic alliance and therapist competence demonstrated to be important
      treatment delivery factors in psychotherapy for health anxiety. A stronger
      consideration of those processes during psychotherapy for health anxiety might be
      able to improve psychotherapy outcome. 

PMID- 25977074
TI  - Recent advances in pancreatic cancer: biology, treatment, and prevention.
AB  - Pancreatic cancer (PC) is the fourth leading cause of cancer-related death in
      United States. Efforts have been made towards the development of the viable
      solution for its treatment with constrained accomplishment because of its complex
      biology. It is well established that pancreatic cancer stem cells (CSCs), albeit
      present in a little count, contribute incredibly to PC initiation, progression,
      and metastasis. Customary chemo and radiotherapeutic alternatives, however,
      expands general survival, the related side effects are the significant concern.
      Amid the most recent decade, our insight about molecular and cellular pathways
      involved in PC and role of CSCs in its progression has increased enormously.
      Presently the focus is to target CSCs. The herbal products have gained much
      consideration recently as they, usually, sensitize CSCs to chemotherapy and
      target molecular signaling involved in various tumors including PC. Some planned
      studies have indicated promising results proposing that examinations in this
      course have a lot to offer for the treatment of PC. Although preclinical studies
      uncovered the importance of herbal products in attenuating pancreatic carcinoma,
      limited studies have been conducted to evaluate their role in clinics. The
      present review provides a new insight to recent advances in pancreatic cancer
      biology, treatment and current status of herbal products in its anticipation. 

PMID- 25977075
TI  - Roles and activities of chromatin remodeling ATPases in plants.
AB  - Chromatin remodeling ATPases and their associated complexes can alter the
      accessibility of the genome in the context of chromatin by using energy derived
      from the hydrolysis of ATP to change the positioning, occupancy and composition
      of nucleosomes. In animals and plants, these remodelers have been implicated in
      diverse processes ranging from stem cell maintenance and differentiation to
      developmental phase transitions and stress responses. Detailed investigation of
      their roles in individual processes has suggested a higher level of selectivity
      of chromatin remodeling ATPase activity than previously anticipated, and diverse
      mechanisms have been uncovered that can contribute to the selectivity. This
      review summarizes recent advances in understanding the roles and activities of
      chromatin remodeling ATPases in plants. 

PMID- 25977077
TI  - Readiness Enhancement Management Strategies (REMS): a proof of concept and
      evaluation feasibility study of staff training to improve service engagement by
      people with personality difficulties.
AB  - One third of people diagnosed with PD do not complete treatment and non
      completion is associated with poorer clinical outcomes. Equipping staff to be
      better able to engage this client group is important, and web-based, self
      directed learning is a potentially cost-effective way to train staff. This study
      examined the implementation of a web-based training programme called Readiness
      Enhancement Management Strategies (REMS) in three types of service. Completion
      rates were 94.4% in community health services; 92.3% in prison offender health
      services; and 46.5% in probation services. Staff found the content of REMS
      acceptable and useful. This study demonstrated that staff in NHS and criminal
      justice settings can complete REMS, but staff in probation services are
      challenged by time pressures and limited computer access. Staff at probation
      sites were less familiar with PD issues compared with the NHS staff. A web-based
      staff training programme called Readiness Enhancement Management Strategies
      (REMS) was developed to promote the engagement of people with personality
      difficulties in treatment. This 'proof of concept' study examined the REMS
      implementation process, its acceptability and the feasibility of using service
      data for future evaluation. Staff in six services working with people diagnosed
      with personality disorder or undiagnosed people with personality difficulties
      were eligible to participate: two community health services, two prison offender
      health services and two probation services. Of 92 eligible staff, 74 were
      available to undertake REMS. These staff completed knowledge and acceptability
      surveys and rated service user engagement with treatment. The proportion of
      treatment sessions attended by service users was collected for a 30-week period.
      REMS completion rates were community - 94.4%, prison - 92.3% and probation -
      46.5%. Three quarters of participants rated REMS as 7 out of 10 or higher. All
      teams were able to provide service data for the study period. REMS can be
      implemented by National Health Services (NHS) staff in community and prison
      settings, but technology issues need to be resolved in probation services. REMS
      may be useful for NHS staff working with difficult to engage clients, and an
      evaluation is a feasible prospect.

PMID- 25977076
TI  - Novel model of innate immunity in corneal infection.
AB  - The cornea functions as the major refractive interface for vision and protects
      the internal eye from insult. Current understanding of innate immune responses to
      corneal infection derives from a synthesis of in vitro and in vivo analyses.
      However, monolayer cell cultures and mouse models do not accurately duplicate all
      aspects of innate immunity in human patients. Here, we describe a three
      dimensional culture system that incorporates human cells and extracellular matrix
      to more completely simulate the human cornea for studies of infection. Human
      corneal stromal fibroblasts were mixed with type I collagen in 3-MUm pore size
      transwell inserts, and overlayed with Matrigel to simulate a human corneal stroma
      and epithelial basement membrane. These were then infected with a cornea-tropic
      adenovirus, and exposed on their inferior side to leukocytes derived from human
      peripheral blood. Subsequent analyses were performed with histology, confocal
      microscopy, ELISA, and fluorescence-activated cell sorting (FACS). CXCL8, a
      neutrophil chemokine shown previously as the first cytokine induced in infection
      of human corneal cells, increased upon adenovirus infection of facsimiles in a
      dose-responsive fashion. Myeloperoxidase-positive cells infiltrated infected
      corneal facsimiles in a sub-Matrigel location, possibly due to CXCL8
      colocalization with heparan sulfate, a Matrigel constituent. Cellular
      infiltration was significantly inhibited by treatment with chemical inhibitors of
      p38 MAPK and Src kinase, both constituents of a signaling cascade previously
      suggested to regulate inflammation after adenovirus infection. FACS analysis
      determined that both virus and corneal fibroblasts were necessary for the
      induction of leukocyte migration into the facsimiles. The corneal facsimile,
      literally a cornea in a test tube, permits mechanistic studies on human tissue in
      a highly tractable system. 

PMID- 25977078
TI  - Methods for delivering and evaluating the efficacy of cognitive enhancement.
AB  - Cognitive deficits are related to impaired everyday functioning in multiple
      conditions and in healthy individuals. Treatment of cognitive functioning can be
      facilitated through either pharmacological or remediation strategies. The
      critical goals of cognitive enhancement are to improve everyday functioning in
      multiple domains. This chapter describes the strategies that are most desirable
      for the treatment of cognitive impairments and detection of potential benefits of
      treatment in cognitive and functional domains. These strategies include the use
      of performance-based assessments of cognition and functioning and the appropriate
      use of observational strategies to detect changes. Finally, we define several
      outcome-related goals and discuss the practicality of their measurement. 

PMID- 25977079
TI  - Animal paradigms to assess cognition with translation to humans.
AB  - Cognition is a complex brain function that represents processes such as learning
      and memory, attention, working memory, and executive functions amongst others.
      Impairments in cognition are prevalent in many neuropsychiatric and neurological
      disorders with few viable treatment options. The development of new therapies is
      challenging, and poor efficacy in clinical development continues to be one of the
      most consistent reasons compounds fail to advance, suggesting that traditional
      animal models are not predictive of human conditions and behavior. An effort to
      improve the construct validity of neuropsychological testing across species with
      the intent of facilitating therapeutic development has been strengthening over
      recent years. With an emphasis on understanding the underlying biology,
      optimizing the use of appropriate systems (e.g., transgenic animals) to model
      targeted disease states, and incorporating non-rodent species (e.g., non-human
      primates) that may enable a closer comparison to humans, an improvement in the
      translatability of the results will be possible. This chapter focuses on some
      promising translational cognitive paradigms for use in rodents, non-human
      primates, and humans. 

PMID- 25977080
TI  - Signaling pathways relevant to cognition-enhancing drug targets.
AB  - Aging is generally associated with a certain cognitive decline. However,
      individual differences exist. While age-related memory deficits can be observed
      in humans and rodents in the absence of pathological conditions, some individuals
      maintain intact cognitive functions up to an advanced age. The mechanisms
      underlying learning and memory processes involve the recruitment of multiple
      signaling pathways and gene expression, leading to adaptative neuronal plasticity
      and long-lasting changes in brain circuitry. This chapter summarizes the current
      understanding of how these signaling cascades could be modulated by cognition
      enhancing agents favoring memory formation and successful aging. It focuses on
      data obtained in rodents, particularly in the rat as it is the most common animal
      model studied in this field. First, we will discuss the role of the excitatory
      neurotransmitter glutamate and its receptors, downstream signaling effectors
      [e.g., calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase C
      (PKC), extracellular signal-regulated kinases (ERK), mammalian target of
      rapamycin (mTOR), cAMP response element-binding protein (CREB)], associated
      immediate early gene (e.g., Homer 1a, Arc and Zif268), and growth factors
      [insulin-like growth factors (IGFs) and brain-derived neurotrophic factor (BDNF)]
      in synaptic plasticity and memory formation. Second, the impact of the
      cholinergic system and related modulators on memory will be briefly reviewed.
      Finally, since dynorphin neuropeptides have recently been associated with memory
      impairments in aging, it is proposed as an attractive target to develop novel
      cognition-enhancing agents.

PMID- 25977081
TI  - Role of adult hippocampal neurogenesis in cognition in physiology and disease:
      pharmacological targets and biomarkers.
AB  - Adult hippocampal neurogenesis is a remarkable form of brain structural
      plasticity by which new functional neurons are generated from adult neural stem
      cells/precursors. Although the precise role of this process remains elusive,
      adult hippocampal neurogenesis is important for learning and memory and it is
      affected in disease conditions associated with cognitive impairment, depression,
      and anxiety. Immature neurons in the adult brain exhibit an enhanced structural
      and synaptic plasticity during their maturation representing a unique population
      of neurons to mediate specific hippocampal function. Compelling preclinical
      evidence suggests that hippocampal neurogenesis is modulated by a broad range of
      physiological stimuli which are relevant in cognitive and emotional states.
      Moreover, multiple pharmacological interventions targeting cognition modulate
      adult hippocampal neurogenesis. In addition, recent genetic approaches have shown
      that promoting neurogenesis can positively modulate cognition associated with
      both physiology and disease. Thus the discovery of signaling pathways that
      enhance adult neurogenesis may lead to therapeutic strategies for improving
      memory loss due to aging or disease. This chapter endeavors to review the
      literature in the field, with particular focus on (1) the role of hippocampal
      neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic
      signals that modulate hippocampal neurogenesis with a focus on pharmacological
      targets; and (3) efforts toward novel strategies pharmacologically targeting
      neurogenesis and identification of biomarkers of human neurogenesis. 

PMID- 25977082
TI  - Attention.
AB  - The ability to focus one's attention on important environmental stimuli while
      ignoring irrelevant stimuli is fundamental to human cognition and intellectual
      function. Attention is inextricably linked to perception, learning and memory,
      and executive function; however, it is often impaired in a variety of
      neuropsychiatric disorders, including Alzheimer's disease, schizophrenia,
      depression, and attention deficit hyperactivity disorder (ADHD). Accordingly,
      attention is considered as an important therapeutic target in these disorders.
      The purpose of this chapter is to provide an overview of the most common
      behavioral paradigms of attention that have been used in animals (particularly
      rodents) and to review the literature where these tasks have been employed to
      elucidate neurobiological substrates of attention as well as to evaluate novel
      pharmacological agents for their potential as treatments for disorders of
      attention. These paradigms include two tasks of sustained attention that were
      developed as rodent analogues of the human Continuous Performance Task (CPT), the
      Five-Choice Serial Reaction Time Task (5-CSRTT) and the more recently introduced
      Five-Choice Continuous Performance Task (5C-CPT), and the Signal Detection Task
      (SDT) which was designed to emphasize temporal components of attention. 

PMID- 25977083
TI  - Executive function.
AB  - Components of human executive function, like rule generation and selection in
      response to stimuli (attention set-shifting) or overcoming a habit (reversal
      learning), can be reliably modelled in rodents. The rodent paradigms are based
      upon tasks that assess cognitive flexibility in clinical populations and have
      been effective in distinguishing the neurobiological substrates and the
      underlying neurotransmitter systems relevant to executive function. A review of
      the literature on the attentional set-shifting task highlights a prominent role
      for the medial region of the prefrontal cortex in the ability to adapt to a new
      rule (extradimensional shift) while the orbitofrontal cortex has been associated
      with the reversal learning component of the task. In other paradigms specifically
      developed to examine reversal learning in rodents, the orbitofrontal cortex also
      plays a prominent role. Modulation of dopamine, serotonin, and glutamatergic
      receptors can disrupt executive function, a feature commonly exploited to develop
      concepts underlying psychiatric disorders. While these paradigms do have
      excellent translational construct validity, they have been less effective as
      predictive preclinical models for cognitive enhancers, especially for cognition
      in health subjects. Accordingly, a more diverse battery of tasks may be necessary
      to model normal human executive function in the rodent for drug development. 

PMID- 25977084
TI  - Declarative memory.
AB  - Declarative Memory consists of memory for events (episodic memory) and facts
      (semantic memory). Methods to test declarative memory are key in investigating
      effects of potential cognition-enhancing substances--medicinal drugs or
      nutrients. A number of cognitive performance tests assessing declarative episodic
      memory tapping verbal learning, logical memory, pattern recognition memory, and
      paired associates learning are described. These tests have been used as outcome
      variables in 34 studies in humans that have been described in the literature in
      the past 10 years. Also, the use of episodic tests in animal research is
      discussed also in relation to the drug effects in these tasks. The results show
      that nutritional supplementation of polyunsaturated fatty acids has been
      investigated most abundantly and, in a number of cases, but not all, show
      indications of positive effects on declarative memory, more so in elderly than in
      young subjects. Studies investigating effects of registered anti-Alzheimer drugs,
      cholinesterase inhibitors in mild cognitive impairment, show positive and
      negative effects on declarative memory. Studies mainly carried out in healthy
      volunteers investigating the effects of acute dopamine stimulation indicate
      enhanced memory consolidation as manifested specifically by better delayed
      recall, especially at time points long after learning and more so when drug is
      administered after learning and if word lists are longer. The animal studies
      reveal a different picture with respect to the effects of different drugs on
      memory performance. This suggests that at least for episodic memory tasks, the
      translational value is rather poor. For the human studies, detailed parameters of
      the compositions of word lists for declarative memory tests are discussed and it
      is concluded that tailored adaptations of tests to fit the hypothesis under
      study, rather than "off-the-shelf" use of existing tests, are recommended.

PMID- 25977085
TI  - Verbal memory.
AB  - Verbal memory is impaired in neurological and psychiatric conditions and provides
      one of the main targets of intervention. Specifically, this cognitive domain has
      been shown to provide a major determinant of outcome in schizophrenia and mood
      disorders. Therefore, verbal memory disturbances should be focused in the
      development of novel pharmacological and psychosocial therapeutics. Effective
      integration between preclinical and clinical studies should provide a key to the
      pursuit of drugs enhancing verbal memory. 

PMID- 25977086
TI  - Emotional memory.
AB  - Research on the reconsolidation effect was greatly revitalized by the highly
      analytic demonstration of memory reconsolidation (Nader et al. Nature 406:722
      726, 2000) in a well-defined behavioral protocol (auditory fear conditioning in
      the rat). Since this study, reconsolidation has been demonstrated in hundreds of
      studies over a range of species, tasks, and amnesic agents. Evidence for
      reconsolidation does not come solely from the behavioral level of analysis.
      Cellular and molecular correlates of reconsolidation have also been found. In
      this chapter, I will first define the evidence on which reconsolidation is
      concluded to exist. I will then discuss some of the conceptual issues facing the
      field in determining when reconsolidation does and does not occur. Lastly I will
      explain the clinical implications of this effect. 

PMID- 25977087
TI  - Social cognition.
AB  - Social cognition is a major problem underlying deficiencies in interpersonal
      relationships in several psychiatric populations. And yet there is currently no
      gold standard for pharmacological treatment of psychiatric illness that directly
      targets these social cognitive areas. This chapter serves to illustrate some of
      the most innovative attempts at pharmacological modulation of social cognition in
      psychiatric illnesses including schizophrenia, borderline personality disorder,
      autism spectrum disorders, antisocial personality disorder and psychopathy,
      social anxiety disorder, and posttraumatic stress disorder. Pharmacological
      modulation includes studies administering oxytocin, ecstasy (MDMA), modafinil,
      methylphenidate, and D-cycloserine. Furthermore, some background on social
      cognition research in healthy individuals, which could be helpful in developing
      future treatments, is provided as well as the potential for each drug as a long
      term treatment option. 

PMID- 25977088
TI  - Neural targets in the study and treatment of social cognition in autism spectrum
      disorder.
AB  - The purpose of this chapter is to present results from recent research on social
      cognition in autism spectrum disorder (ASD). The clinical phenomenology and
      neuroanatomical circuitry of ASD are first briefly described. The
      neuropharmacology of social cognition in animal models of ASD and humans is then
      addressed. Next, preclinical and clinical research on the neurohormone oxytocin
      is reviewed. This is followed by a presentation of results from preclinical and
      clinical studies on the excitatory amino acid glutamate. Finally, the role of
      neuroinflammation in ASD is addressed from the perspectives of preclinical
      neuroscience and research involving humans with ASD. 

PMID- 25977089
TI  - Assessing cognitive improvement in people with Down syndrome: important
      considerations for drug-efficacy trials.
AB  - Experimental research over just the past decade has raised the possibility that
      learning deficits connected to Down syndrome (DS) might be effectively managed by
      medication. In the current chapter, we touch on some of the work that paved the
      way for these advances and discuss the challenges associated with translating
      them. In particular, we highlight sources of phenotypic variability in the DS
      population that are likely to impact performance assessments. Throughout,
      suggestions are made on how to detect meaningful changes in cognitive-adaptive
      function in people with DS during drug treatment. The importance of within
      subjects evaluation is emphasized. 

PMID- 25977090
TI  - Pharmacological disruption of maladaptive memory.
AB  - Many psychiatric disorders are characterized by intrusive, distracting, and
      disturbing memories that either perpetuate the illness or hinder successful
      treatment. For example, posttraumatic stress disorder (PTSD) involves such strong
      reemergence of memories associated with a traumatic event that the individual
      feels like the event is happening again. Furthermore, drug addiction is
      characterized by compulsive use and repeated relapse that is often driven by
      internal memories of drug use and/or by exposure to external stimuli that were
      associated with drug use. Therefore, identifying pharmacological methods to
      weaken the strength of maladaptive memories is a major goal of research efforts
      aimed at finding new treatments for these disorders. The primary mechanism by
      which memories could be pharmacologically disrupted or altered is through
      manipulation of memory reconsolidation. Reconsolidation occurs when an
      established memory is remembered or reactivated, reentering a labile state before
      again being consolidated into long-term memory storage. Memories are subject to
      disruption during this labile state. In this chapter we will discuss the
      preclinical and clinical studies identifying potential pharmacological methods
      for disrupting the integrity of maladaptive memory to treat mental illness. 

PMID- 25977091
TI  - Non-pharmacological Approaches to Cognitive Enhancement.
AB  - Pharmaceuticals and medical devices hold the promise of enhancing brain function,
      not only of those suffering from neurodevelopmental, neuropsychiatric or
      neurodegenerative illnesses, but also of healthy individuals. However, a number
      of lifestyle interventions are proven cognitive enhancers, improving attention,
      problem solving, reasoning, learning and memory or even mood. Several of these
      interventions, such as physical exercise, cognitive, mental and social
      stimulation, may be described as environmental enrichments of varying types. Use
      of these non-pharmacological cognitive enhancers circumvents some of the ethical
      considerations associated with pharmaceutical or technological cognitive
      enhancement, being low in cost, available to the general population and
      presenting low risk to health and well-being. In this chapter, there will be
      particular focus on the effects of exercise and enrichment on learning and memory
      and the evidence supporting their efficacy in humans and in animal models will be
      described. 

PMID- 25977092
TI  - Optogenetics and deep brain stimulation neurotechnologies.
AB  - Brain neural network is composed of densely packed, intricately wired neurons
      whose activity patterns ultimately give rise to every behavior, thought, or
      emotion that we experience. Over the past decade, a novel neurotechnique,
      optogenetics that combines light and genetic methods to control or monitor neural
      activity patterns, has proven to be revolutionary in understanding the functional
      role of specific neural circuits. We here briefly describe recent advance in
      optogenetics and compare optogenetics with deep brain stimulation technology that
      holds the promise for treating many neurological and psychiatric disorders. 

PMID- 25977093
TI  - Closing thoughts for cognitive enhancement.
AB  - The wide-ranging field of cognition enhancing research along with its ethics as
      it stands today is summarized. In the forefront are potentially novel drugs and
      non-pharmacological treatments for cognitive impairment across many different
      psychiatric and neurologic indications. Today's research will bring new drugs to
      patients tomorrow, and tomorrow's research will bring new molecular targets to
      clinical development that should be cognitive domain-specific. There is the
      likelihood that special populations may be better treated and that personalized
      medicine for cognitive impairment could become a reality. It is conceivable that
      with the current research effort, cognition enhancing drugs will become available
      to wide-ranging populations of people with neuropsychiatric illness and to those
      that are healthy. In some cultures, there is a push in society to be more
      intelligent or have more cognitive prowess. Thus, the ethical use of cognitive
      enhancing drugs should be an area of debate and communication. Neuroethics is a
      growing field and it intends to bring together key contributors such as
      physicians, disease experts, regulatory officials, and policy makers to discuss
      how such medicines can or should be made available. Together with this, one has
      to consider the possibility that no single medicine or technology will have a
      great impact on cognition and, therefore, combination therapy of drugs plus other
      approaches like exercise or transcranial direct-current stimulation may be the
      path forward. This is another area of scientific inquiry and debate, and the
      results should be fruitful and helpful to patients. The science of cognition is
      advancing at a rapid rate, and communication of its progress along with the
      development of rational and ethical policies for use of cognitive enhancers will
      be beneficial. 

PMID- 25977094
TI  - Activity of lipo-cyclic gamma-AApeptides against biofilms of Staphylococcus
      epidermidis and Pseudomonas aeruginosa.
AB  - Antibiotic resistant bacterial infection is currently a serious public concern.
      Their ability to form biofilms further complicates the treatment. Herein we
      investigated the activity of lipo-cyclic gamma-AApeptides against both planktonic
      cells and biofilms of Staphylococcus epidermidis and Pseudomonas aeruginosa, in
      comparison to those of the conventional antibiotic ciprofloxacin. Our results
      suggest that these lipo-cyclic gamma-AApeptides exhibit comparable or enhanced
      performance compared to ciprofloxacin in the prevention of biofilm formation for
      both Gram-positive and Gram-negative bacteria, providing a potential alternative
      treatment and prevention for indwelling device-related infections. 

PMID- 25977095
TI  - Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues
      of the natural product formononetin.
AB  - The synthesis and antimycobacterial activity of formononetin analogues is hereby
      reported. Formononetin and its analogue 11E showed 88% and 95% growth inhibition,
      respectively, against the H37Rv strain of Mycobacterium tuberculosis.
      Pharmacophore modeling studies indicated that the presence of a hydroxyl group in
      formononetin and its analogues, is crucial for maintaining activity. 

PMID- 25977097
TI  - CASPR2 forms a complex with GPR37 via MUPP1 but not with GPR37(R558Q), an autism
      spectrum disorder-related mutation.
AB  - Autism spectrum disorder (ASD) is a developmental brain disorder. Mutations in
      synaptic components including synaptic adhesion molecules have been found in ASD
      patients. Contactin-associated protein-like 2 (CASPR2) is one of the synaptic
      adhesion molecules associated with ASD. CASPR2 forms a complex with receptors via
      interaction with multiple PDZ domain protein 1 (MUPP1). Little is known about the
      relationship between impaired CASPR2-MUPP1-receptor complex and the pathogenesis
      of ASD. GPR37 is a receptor for survival factors. We recently identified
      mutations including R558Q in the G-protein-coupled receptor 37 (GPR37) gene in
      ASD patients. The mutated GPR37s accumulate in the endoplasmic reticulum. In this
      study, we show that GPR37 is a component of the CASPR2-MUPP1 receptor complex in
      the mouse brain. CASPR2 and GPR37 mainly interacted with the PDZ3 and PDZ11
      domains of MUPP1, respectively. Compared to GPR37, GPR37(R558Q) slightly
      interacted with MUPP1 and caused dendritic alteration. GPR37, but not
      GPR37(R558Q) nor GPR37-deltaC which lacks its PDZ binding domain, was transported
      to the cell surface by MUPP1. In primary hippocampal neurons, GPR37 co-localized
      with MUPP1 and CASPR2 at the synapse, but not GPR37(R558Q). Thus, ASD-related
      mutation of GPR37 may cause the impaired CASPR2-MUPP1-GPR37 complex on the
      dendrites associated with one of the pathogenesis of ASD. In this study, we
      identified that GPR37 is a component of the MUPP1 and CASPR2 receptor complex.
      Autism deleterious mutated GPR37(R558Q) slightly interacts with MUPP1 and retains
      in ER, resulting in dendritic alteration. In neuron, GPR37, but not GPR37(R558Q),
      is transported to the dendrite and synapse by MUPP1. Thus, ASD-related mutation
      of GPR37 may cause the impaired CASPR2-MUPP1-GPR37 complex on the dendrites
      associated with one of the pathogenesis of ASD. 

PMID- 25977098
TI  - Chronic inflammatory demyelinating polyneuropathy with membranous nephropathy.

PMID- 25977099
TI  - Water Pie: Creativity and Leadership in Academic Psychiatry.

PMID- 25977096
TI  - Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an
      analysis of cohorts participating in the CHANCES consortium.
AB  - The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with
      total and site-specific cancer incidence have been examined in several
      epidemiological studies with overall inconclusive findings. Very little is known
      about the association of vitamin D with cancer incidence in older populations. We
      assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of
      all cancers combined and incidence of lung, colorectal, breast, prostate and
      lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations
      and cancer incidence were available in total for 15,486 older adults (mean age
      63, range 50-84 years) participating in two cohort studies: ESTHER (Germany) and
      TROMSO (Norway); and a subset of previously published nested-case control data
      from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain
      and Sweden) from the CHANCES consortium on health and aging. Cox proportional
      hazards or logistic regression were used to derive multivariable adjusted hazard
      and odds ratios, respectively, and their 95% confidence intervals across 25(OH)D
      categories. Meta-analyses with random effects models were used to pool study
      specific risk estimates. Overall, lower 25(OH)D concentrations were not
      significantly associated with increased incidence of most of the cancers
      assessed. However, there was some evidence of increased breast cancer and
      decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses
      with individual participant data from three large European population-based
      cohort studies provide at best limited support for the hypothesis that vitamin D
      may have a major role in cancer development and prevention among European older
      adults.

PMID- 25977100
TI  - Improving Psychiatrists' Attitudes Towards Individuals with Psychotic Disorders
      and Co-Occurring Substance Use Disorders.

PMID- 25977101
TI  - Reducao de volume pulmonar broncoscopico no enfisema em estadio terminal.
      Resultados dos primeiros 98 doentes.

PMID- 25977102
TI  - Recomendacoes sobre o uso dos testes de exercicio na pratica clinica.

PMID- 25977103
TI  - DPOC associada a um aumento de mortalidade em doentes com pneumonia adquirida na
      comunidade.

PMID- 25977104
TI  - Suplemento de oxigenio necessario em voluntarios saudaveis quando submetidos a
      broncoscopia com lavado broncoalveolar.

PMID- 25977105
TI  - Terapeutica clinica - Insulina inalada para a diabetes mellitus.

PMID- 25977106
TI  - Connecting narrative with mental health learning through discussion and analysis
      of selected contemporary films.
AB  - In a recently completed qualitative study of nursing leaders' views of
      requirements for practice, seven aspects of recovery practice were revealed as
      central for graduates to learn. It is challenging to provide an in-depth
      understanding of recovery in a nursing curriculum because there are so many
      competing content areas and, as a result, time is constrained. However, because
      it is so vital to understand, educators would benefit from developing and sharing
      teaching strategies that explore recovery deeply, memorably, and engagingly, in
      order to encourage theory to be put into practice. Recent research into narrative
      pedagogy suggests that better use of stories, especially those that have strong
      emotional pull, such as well-made films and memoirs, may offer solutions to
      creative educators. Stories can have transformative potential, because once heard
      and heeded, the person can never go back to exactly how they were before.
      Recovery learned in this way becomes a threshold concept for the mental health
      curriculum. This paper outlines an engaging and time-efficient teaching strategy
      to develop these skills, drawing on the concept of narrative pedagogy. 

PMID- 25977107
TI  - Does cerebrospinal fluid analysis add predictive value to magnetic resonance
      imaging for long term irreversible disability in patients with early multiple
      sclerosis?
AB  - BACKGROUND: The independent prognostic value of cerebrospinal fluid analysis in
      multiple sclerosis is not established. OBJECTIVE: To determine the prognostic
      value of intrathecal synthesis in a cohort of patients with relapsing-onset MS
      taking into consideration demographic and imaging parameters. METHODS: In this
      prospective cohort study conducted from 1993 to 2013, we analyzed the time to
      confirmed disability (persistent above 6 months) and irreversible disability
      (persistent for the entire disease course) of two disability milestones, Expanded
      Disability Status Scale score >= 4 or 6, and the time to secondary progressive
      onset in 579 patients with relapsing-onset multiple sclerosis. Demographic
      parameters (age at onset, gender) and imaging parameters (periventricular
      lesions) were included in the Cox models. RESULTS: 447 patients (77.2%) had
      intrathecal synthesis (oligoclonal bands and/or increased immunoglobulin G index
      value). No statistically significant relation was found between intrathecal
      synthesis and the time to reach each disability milestone or secondary
      progressive onset. An age older than 40 years and more than 3 periventricular
      lesions predicted a worse prognosis. CONCLUSIONS: Cerebrospinal fluid analysis
      did not predict the time to disability milestones in relapsing-onset multiple
      sclerosis independently of age and imaging data.

PMID- 25977108
TI  - Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a beta1
      Selective Blocker.
AB  - A new chemoenzymatic route is reported to synthesize acebutolol, a selective
      beta1 adrenergic receptor blocking agent in enantiopure (R and S) forms. The
      enzymatic kinetic resolution strategy was used to synthesize enantiopure
      intermediates (R)- and (S)-N-(3-acetyl-4-(3-chloro-2
      hydroxypropoxy)phenyl)butyramide from the corresponding racemic alcohols. The
      results showed that out of eleven commercially available lipase preparations, two
      enzyme preparations (Lipase A, Candida antarctica, CLEA [CAL CLEA] and Candida
      rugosa lipase, 62316 [CRL 62316]) act in enantioselective manner. Under optimized
      conditions the enantiomeric excess of both (R)- and (S)-N-(3-acetyl-4-(3-chloro-2
      hydroxypropoxy)phenyl)butyramide were 99.9 and 96.8%, respectively. N-alkylation
      of both the (R) and (S) intermediates with isopropylamine gave enantiomerically
      pure (R and S)- acebutolol with a yield 68 and 72%, respectively. This study
      suggests a high yielding, easy and environmentally green approach to synthesize
      enantiopure acebutolol.

PMID- 25977109
TI  - Melanoma's next top model, it is in the air.

PMID- 25977110
TI  - Pulmonary atresia with double ductus arteriosus.
AB  - We present the case of a neonate with pulmonary atresia and persistent bilateral
      patent ductus arteriosus imaged by gated multidetector CT. Traditionally, these
      patients have been assessed preoperatively with invasive angiocardiography or
      with cardiovascular magnetic resonance under sedation. Our case illustrates that
      contemporary cardiovascular CT techniques can now be used for preoperative
      evaluation with minimal radiation penalty, obviating the risks of sedation or
      cardiac catheterization. 

PMID- 25977112
TI  - Anomalous hepatic vein drainage into a giant left atrium.
AB  - A 56-year-old man with a history of complex atrial-septal defect repair, atrial
      fibrillation, and severe mitral regurgitation presented with progressive
      shortness of breath. A cardiac CT examination was done as part of a preoperative
      protocol before mitral valve replacement and it showed a severely enlarged left
      atrium and an anomalous hepatic vein draining into the left atrium. These
      findings were totally unsuspected and changed the patient management,
      highlighting the benefit of cardiac CT beyond the coronary finding. 

PMID- 25977111
TI  - Combined coronary angiography and myocardial perfusion by computed tomography in
      the identification of flow-limiting stenosis - The CORE320 study: An integrated
      analysis of CT coronary angiography and myocardial perfusion.
AB  - BACKGROUND: The combination of coronary CT angiography (CTA) and myocardial CT
      perfusion (CTP) is gaining increasing acceptance, but a standardized approach to
      be implemented in the clinical setting is necessary. OBJECTIVES: To investigate
      the accuracy of a combined coronary CTA and myocardial CTP comprehensive protocol
      compared to coronary CTA alone, using a combination of invasive coronary
      angiography and single photon emission CT as reference. METHODS: Three hundred
      eighty-one patients included in the CORE320 trial were analyzed in this study.
      Flow-limiting stenosis was defined as the presence of >=50% stenosis by invasive
      coronary angiography with a related perfusion defect by single photon emission
      CT. The combined CTA + CTP definition of disease was the presence of a >=50%
      stenosis with a related perfusion defect. All data sets were analyzed by 2
      experienced readers, aligning anatomic findings by CTA with perfusion defects by
      CTP. RESULTS: Mean patient age was 62 +/- 6 years (66% male), 27% with prior
      history of myocardial infarction. In a per-patient analysis, sensitivity for CTA
      alone was 93%, specificity was 54%, positive predictive value was 55%, negative
      predictive value was 93%, and overall accuracy was 69%. After combining CTA and
      CTP, sensitivity was 78%, specificity was 73%, negative predictive value was 64%,
      positive predictive value was 0.85%, and overall accuracy was 75%. In a per
      vessel analysis, overall accuracy of CTA alone was 73% compared to 79% for the
      combination of CTA and CTP (P < .0001 for difference). CONCLUSIONS: Combining
      coronary CTA and myocardial CTP findings through a comprehensive protocol is
      feasible. Although sensitivity is lower, specificity and overall accuracy are
      higher than assessment by coronary CTA when compared against a reference standard
      of stenosis with an associated perfusion defect.

PMID- 25977113
TI  - Cardiopulmonary manifestations of isolated pulmonary valve infective endocarditis
      demonstrated with cardiac CT.
AB  - Right-sided infective endocarditis involving the pulmonary valve is rare. This
      pictorial essay discusses the use and findings of cardiac CT combined with
      delayed chest CT and noncontrast chest CT of pulmonary valve endocarditis.
      Cardiac CT is able to show the full spectrum of right-sided endocarditis
      cardiopulmonary features including manifestations that cannot be demonstrated by
      echocardiography. 

PMID- 25977114
TI  - Relationship of epicardial fat volume from noncontrast CT with impaired
      myocardial flow reserve by positron emission tomography.
AB  - BACKGROUND: Impaired myocardial flow reserve (MFR) is a marker of coronary
      vascular dysfunction with prognostic significance. OBJECTIVES: We aimed to
      investigate the relationship between epicardial fat volume (EFV) measured from
      noncontrast CT and impaired MFR derived from rest-stress Rb-82 positron emission
      tomography (PET). METHODS: We retrospectively studied 85 consecutive patients
      without known coronary artery disease who underwent rest-stress Rb-82 myocardial
      PET/CT and were subsequently referred for invasive coronary angiography. EFV was
      computed from noncontrast CT by validated software and indexed to body surface
      area (EFVi, cm3/m2). Global stress and rest MFR were automatically derived from
      PET. Patient age, sex, cardiovascular risk factors, coronary calcium score (CCS),
      and EFVi were combined by boosted ensemble machine learning algorithm into a
      novel composite risk score, using 10-fold cross-validation, to predict impaired
      global MFR (MFR <=2.0) by PET. RESULTS: Patients with impaired MFR (44 of 85;
      52%) were older (71 vs. 65 years; P = .03) and had higher frequency of CCS
      (>=400; P = .02) with significantly higher EFVi (63.1 +/- 20.4 vs. 51.3 +/- 14.1
      cm3/m2; P = .003). On multivariate logistic regression (with age, sex, number of
      risk factors, CCS, and EFVi), EFVi was the only independent predictor of impaired
      MFR (odds ratio, 7.39; P = .02). The machine learning composite risk score
      significantly improved risk reclassification of impaired MFR compared to CCS or
      EFVi alone (integrated discrimination improvement = 0.19; P = .007 and IDI =
      0.22; P = .002, respectively). CONCLUSIONS: Increased EFVi and composite risk
      score combining EFVi and CCS significantly improve identification of impaired
      global MFR by PET.

PMID- 25977115
TI  - Myocardial scar imaging by standard single-energy and dual-energy late
      enhancement CT: Comparison with pathology and electroanatomic map in an
      experimental chronic infarct porcine model.
AB  - BACKGROUND: Myocardial scar is a substrate for ventricular tachycardia and sudden
      cardiac death. Late enhancement CT imaging can detect scar, but it remains
      unclear whether newer late enhancement dual-energy (LE-DECT) acquisition has
      benefit over standard single-energy late enhancement (LE-CT). OBJECTIVE: We aim
      to compare late enhancement CT using newer LE-DECT acquisition and single-energy
      LE-CT acquisitions with pathology and electroanatomic map (EAM) in an
      experimental chronic myocardial infarction (MI) porcine study. METHODS: In 8 pigs
      with chronic myocardial infarction (59 +/- 5 kg), we performed dual-source CT,
      EAM, and pathology. For CT imaging, we performed 3 acquisitions at 10 minutes
      after contrast administration: LE-CT 80 kV, LE-CT 100 kV, and LE-DECT with 2
      postprocessing software settings. RESULTS: Of the sequences, LE-CT 100 kV
      provided the best contrast-to-noise ratio (all P <= .03) and correlation to
      pathology for scar (rho = 0.88). LE-DECT overestimated scar (both P = .02),
      whereas LE-CT images did not (both P = .08). On a segment basis (n = 136), all CT
      sequences had high specificity (87%-93%) and modest sensitivity (50%-67%), with
      LE-CT 100 kV having the highest specificity of 93% for scar detection compared to
      pathology and agreement with EAM (kappa = 0.69). CONCLUSIONS: Standard single
      energy LE-CT, particularly 100 kV, matched better to pathology and EAM than dual
      energy LE-DECT for scar detection. Larger human trials as well as more technical
      studies that optimize varying different energies with newer hardware and software
      are warranted.

PMID- 25977116
TI  - Cost-effectiveness of coronary CT angiography in patients with chest pain:
      Comparison with myocardial single photon emission tomography.
AB  - BACKGROUND: Coronary CT angiography (CCTA) has been proven accurate and is
      incorporated in clinical recommendations for coronary artery disease (CAD)
      diagnosis workup, but cost-effectiveness data, especially in comparison to other
      methods such as myocardial single photon emission CT (SPECT) are insufficient.
      OBJECTIVE: To compare the cost-effectiveness of CCTA and myocardial SPECT in a
      real-world setting. METHODS: We performed a retrospective cohort study on
      consecutive patients with suspected CAD and a pretest probability between 10% and
      90%. Test accuracy was compared by correcting referral bias to coronary
      angiography depending on noninvasive test results based on the Bayes' theorem and
      also by incorporating 1-year follow-up results. Cost-effectiveness was analyzed
      using test accuracy and quality-adjusted life year (QALY). The model using
      diagnostic accuracy used the number of patients accurately diagnosed among 1000
      persons as the effect and contained only expenses for diagnostic testing as the
      cost. In the model using QALY, a decision tree was developed, and the time
      horizon was 1 year. RESULTS: CCTA was performed in 635 patients and SPECT in 997
      patients. An accurate diagnosis per 1000 patients was achieved in 725 patients by
      CCTA vs 661 patients by SPECT. In the model using diagnostic accuracy, CCTA was
      more effective and less expensive than SPECT ($725.38 for CCTA vs $661.46 for
      SPECT). In the model using QALY, CCTA was generally more effective in terms of
      life quality (0.00221 QALY) and cost ($513) than SPECT. However, cost utility
      varied among subgroups, with SPECT outperforming CCTA in patients with a pretest
      probability of 30% to 60% (0.01890 QALY; $113). CONCLUSION: These results suggest
      that CCTA may be more cost-effective than myocardial SPECT.

PMID- 25977117
TI  - Impact of renal impairment on cardiovascular disease mortality after liver
      transplantation for nonalcoholic steatohepatitis cirrhosis.
AB  - BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is an independent risk
      factor for cardiovascular disease (CVD) morbidity after liver transplantation,
      but its impact on CVD mortality is unknown. We sought to assess the impact of
      NASH on CVD mortality after liver transplantation and to predict which NASH
      recipients are at highest risk of a CVD-related death following a liver
      transplant. METHODS: Using the Organ Procurement and Transplantation Network
      database, we examined associations between NASH and post-liver transplant CVD
      mortality, defined as primary cause of death from thromboembolism, arrhythmia,
      heart failure, myocardial infarction or stroke. A physician panel reviewed cause
      of death. RESULTS: Of 48 360 liver transplants (2/2002-12/2011), 5057 (10.5%)
      were performed for NASH cirrhosis. NASH recipients were more likely to be older,
      female, obese, diabetic and have history of renal failure or prior CVD vs. non
      NASH (P < 0.001 for all). Although there was no difference in overall all-cause
      mortality (log-rank P = 0.96), both early (30-day) and long-term CVD-specific
      mortality was increased among NASH recipients (Odds ratio = 1.30, 95% Confidence
      interval (CI): 1.02-1.66; Hazard ratio = 1.42, 95% CI: 1.07-1.41 respectively).
      These associations were no longer significant after adjustment for pre-transplant
      diabetes, renal impairment or CVD. A risk score comprising age >=55, male sex,
      diabetes and renal impairment was developed for prediction of post-liver
      transplant CVD mortality (c-statistic 0.60). CONCLUSION: NASH recipients have an
      increased risk of CVD mortality after liver transplantation explained by a high
      prevalence of comorbid cardiometabolic risk factors that in aggregate identify
      those at highest risk of post-transplant CVD mortality.

PMID- 25977118
TI  - Divergent signaling pathways regulate IL-12 production induced by different
      species of Lactobacilli in human dendritic cells.
AB  - Recent studies have indicated that different strains of Lactobacilli differ in
      their ability to regulate IL-12 production by dendritic cells (DCs), as some
      strains are stronger inducer of IL-12 while other are not and can even inhibit IL
      12 production stimulated by IL-12-inducer Lactobacilli. In this report we
      demonstrate that Lactobacillus reuteri 5289, as previously described for other
      strains of L. reuteri, can inhibit DC production of IL-12 induced by
      Lactobacilllus acidophilus NCFM. Remarkably, L. reuteri 5289 was able to inhibit
      IL-12 production induced not only by Lactobacilli, as so far reported, but also
      by bacteria of different genera, including pathogens. We investigated in human
      DCs the signal transduction pathways involved in the inhibition of IL-12
      production induced by L. reuteri 5289, showing that this potential anti
      inflammatory activity, which is also accompanied by an elevated IL-10 production,
      is associated to a prolonged phosphorilation of ERK1/2 MAP kinase pathway.
      Improved understanding of the immune regulatory mechanisms exerted by
      Lactobacilli is crucial for a more precise employment of these commensal bacteria
      as probiotics in human immune-mediated pathologies, such as allergies or
      inflammatory bowel diseases. 

PMID- 25977119
TI  - Pitfalls in flow cytometric analyses of surfactant-exposed human leukocytes.
AB  - BACKGROUND: Surfactant replacement treatment is the standard of care for the
      prevention and treatment of neonatal respiratory distress syndrome in preterm
      infants and may also improve oxygenation in acute respiratory distress syndrome
      in children, adolescents and adults. Beside surface tension- and mechanical shear
      reducing functions, natural surfactants have been ascribed immunomodulatory
      capacities. Current in vitro studies on immunomodulatory effects of pulmonary
      surfactant preparations on human leukocytes rely on ELISA, Western blot and
      polymerase chain reaction. Data obtained by flow cytometry are missing, so far,
      most likely due to confounding phospholipid residues. Intracellular cytokine flow
      cytometry in surfactant-exposed immune cells would provide information on pro-
      and anti-inflammatory immunomodulation at the single-cell level and would allow
      for integrating detailed immunophenotyping, functional assays and assessment of
      viability. AIM: We implemented a flow cytometry protocol for reliable
      quantitative assessment of in vitro intracellular cytokine production in
      surfactant-exposed human lymphocytes (CD4(+)) and monocytes (CD14(+)). METHODS:
      Two different permeabilization techniques were tested for their ability to
      provide intracellular cytokine staining in surfactant-exposed CD14(+) monocytes
      and CD4(+) lymphocytes. Both a commercially available solution containing saponin
      and ice-cold methanol were used as permeabilization reagents. RESULTS: For both
      cell types, flow cytometry following saponin-based permeabilization revealed
      pronounced unspecific fluorescence signals in surfactant-exposed samples
      overlapping with the fluorescence spectra of the majority of conjugates.
      Autofluorescence of surfactant phospholipid particles interfered significantly
      with reliable quantification of fluorochrome-specific signals and conclusive
      analysis. Implementation of a methanol-based permeabilization protocol resulted
      in the elimination of confounding non-cell particle signals allowing for an
      accurate quantification of intracellular cytokine production. CONCLUSION:
      Reliable detection of intracellular cytokines by flow cytometry may be
      challenging in surfactant-exposed cell samples due to significant
      autofluorescence of aggregated phospholipid particles. This issue has been
      addressed for the first time and may be of high relevance for all types of
      surfactant research. We demonstrate that a methanol-based permeabilization
      approach completely removes interfering fluorescent surfactant micelles and
      allows for correct evaluation of data. The successful removal of confounding
      surfactant phospholipids opens up a wide variety of multiparameter flow
      cytometry; a method that has not been applied in the field of surfactant
      research, yet.

PMID- 25977120
TI  - Soluble ST2 and IL-33: Potential markers of endometriosis in the Tunisian
      population.
AB  - Interleukin-33 is an IL-1 family cytokine which signals via its T1/ST2 receptor,
      and acts as a key regulator of inflammation. This study aims to measure the
      expression of soluble ST2 (sST2) and IL-33 in endometriosis. We investigated
      thirty women with laparoscopic and histopathological confirmed endometriosis and
      20 control women without pelvic pathology. Peripheral blood mononuclear cells and
      peritoneal fluid (PF) were assessed for sST2 and IL-33 levels that are measured
      by sandwich enzyme-linked immunosorbent assay. Peritoneal fluid IL-33 mRNA
      expression was quantified by real-time reverse transcription polymerase chain
      reaction assays. We found that IL-33 levels in PF and in serum were significantly
      higher in patients with endometriosis compared to women without endometriosis (P
      < 0.05). IL-33 increased levels were significantly more important in PF [10.45 +/
      14.33 ng/mL] than in serum [2.68 +/- 1.54 ng/mL] from endometriosis patients.
      Higher levels of IL-33 mRNA expression were detected in PF from patients with
      endometriosis. Soluble ST2 levels in PF were significantly different between
      patients [2.96 +/- 0.98 ng/mL; P < 0.0001] and controls [0.88 +/- 0.076 ng/mL].
      Serum sST2 levels were similarly expressed in endometriosis patients and in
      controls (P > 0.05). Significant correlation was observed between IL-33 and sST2
      levels in PF. In conclusion, IL-33 and sST2 values observed in PF were found to
      correlate with endometriosis severity. Elevated and correlated PF IL-33 and sST2
      levels from patients with endometriosis suggested a potential role as surrogate
      markers of disease activity.

PMID- 25977121
TI  - Developing qualitative methods - or "same old wine in a new bottle".

PMID- 25977122
TI  - Mental Health Consequences of Childhood Physical Abuse in Chinese Populations: A
      Meta-Analysis.
AB  - OBJECTIVE: Childhood physical abuse (CPA) can lead to adverse mental health
      outcomes in adulthood, but its potential impact on Chinese populations is still
      unclear. This meta-analysis is the first to examine the association between CPA
      and mental health outcomes in Chinese populations. STUDY DESIGN: Studies
      published before December 31, 2014 were identified from Embase, CINAHL, Scopus,
      PsycINFO, PubMed, and Chinese National Knowledge Infrastructure databases.
      Studies with data on the association between CPA and mental health outcomes from
      Chinese subjects were included. Twenty-four studies were initially identified but
      two were excluded because of poor quality. Two reviewers independently extracted
      data to generate summary effect sizes using a random-effects meta-analytic model.
      A priori subgroup and sensitivity analyses were performed to evaluate
      heterogeneity and bias in these studies. RESULTS: Our meta-analysis of 22 studies
      found a significant positive association between CPA and overall mental health
      outcomes among all Chinese subjects (pooled effect size: odds ratio [OR] = 2.16,
      95% confidence interval [CI] = [1.87, 2.49]) and among community samples (pooled
      effect size: OR = 2.06, 95% CI [1.71, 2.48]). Based on the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnostic
      criteria, CPA was more strongly associated with Axis II (OR = 2.62, 95% CI [2.13,
      3.22]) than Axis I disorders (OR = 1.85, 95% CI [1.58, 2.17]). CONCLUSIONS: The
      detrimental effects of CPA on mental health outcomes in Chinese populations were
      comparable to, if not more than, the West. Contrary to the Chinese belief that
      physical punishment is a safe way to discipline children, our findings highlight
      the potential harm to mental health and the need to change this parenting
      practice.

PMID- 25977125
TI  - Using Lean-Six Sigma to reduce hemolysis in the emergency care center in a
      collaborative quality improvement project with the hospital laboratory.
AB  - BACKGROUND: As part of a strategic quality improvement plan, laboratory
      management at Sarasota Memorial Health Care System (SMHCS) focused its efforts on
      improving preanalytical work flow and blood collection processes-both negatively
      affected by hemolyzed specimens. When hemolysis is detected in a blood specimen,
      blood may need to be re-collected, resulting in bottlenecks and rework all along
      the value stream. From July through December 2009, hemolysis averaged 9.8% in the
      Emergency Care Center (ECC) and 3.4% housewide. The goal was set to reduce
      hemolysis to 2%. METHODS: The project team identified hemolysis as one of seven
      factors contributing to non-value-added activities and bottlenecks in blood
      collection and preanalytical processes. Observations and interviews helped to
      identify error-prone practices and process variation. To verify the root causes
      of hemolysis, the findings were compared against best practices. The team
      developed a housewide protocol, standardized collection processes, created
      competency-based training, and enhanced ECC hiring practices. RESULTS: During
      December 2010-March 2011, following initial housewide interventions and ECC self
      sustaining solutions, ECC hemolysis decreased by 91%-from 9.8% (423
      hemolyzed/4,295 collected) to 0.88% (58 hemolyzed/6,560 collected). Housewide
      hemolysis decreased by 59%-from 3.4% (2,046 hemolyzed/60,307 collected) to 1.39%
      (619 hemolyzed/44,528 collected). Since the project, hemolysis has continued to
      trend downward; the mean percentage has consistently been < .05% for the ECC and
      < 1% housewide. CONCLUSION: Lean-Six Sigma tools helped to pinpoint hemolysis as
      a key inefficiency in blood collection and preanalytical work flow. Although
      focused on the ECC, the project team standardized blood collection practices and
      instituted quality devices to achieve hemolysis reductions housewide.

PMID- 25977123
TI  - Mothering alone: cross-national comparisons of later-life disability and health
      among women who were single mothers.
AB  - BACKGROUND: Single motherhood is associated with poorer health, but whether this
      association varies between countries is not known. We examine associations
      between single motherhood and poor later-life health in the USA, England and 13
      European countries. METHODS: Data came from 25 125 women aged 50+ who
      participated in the US Health and Retirement Study, the English Longitudinal
      Study of Ageing and Survey of Health, Ageing and Retirement in Europe. We tested
      whether single motherhood at ages 16-49 was associated with increased risk of
      limitations with activities of daily living (ADL), instrumental ADL and fair/poor
      self-rated health in later life. RESULTS: 33% of American mothers had experienced
      single motherhood before age 50, versus 22% in England, 38% in Scandinavia, 22%
      in Western Europe and 10% in Southern Europe. Single mothers had higher risk of
      poorer health and disability in later life than married mothers, but associations
      varied between countries. For example, risk ratios for ADL limitations were 1.51
      (95% CI 1.29 to 1.98) in England, 1.50 (1.10 to 2.05) in Scandinavia and 1.27
      (1.17 to 1.40) in the USA, versus 1.09 (0.80 to 1.47) in Western Europe, 1.13
      (0.80 to 1.60) in Southern Europe and 0.93 (0.66 to 1.31) in Eastern Europe.
      Women who were single mothers before age 20, for 8+ years, or resulting from
      divorce or non-marital childbearing, were at particular risk. CONCLUSIONS: Single
      motherhood during early-adulthood or mid-adulthood is associated with poorer
      health in later life. Risks were greatest in England, the USA and Scandinavia.
      Selection and causation mechanisms might both explain between-country variation.

PMID- 25977126
TI  - Monitoring the harm associated with use of anticoagulants in pediatric
      populations through trigger-based automated adverse-event detection.
AB  - BACKGROUND: The safety profile of anticoagulants, which are being used with
      increasing frequency in pediatric populations, is not well studied. Automatic
      triggers built into electronic health record systems (EHR) have been shown to be
      an effective way to monitor for and identify medication errors. Anticoagulant
      associated adverse events were examined through the use of an anticoagulant
      trigger panel. METHODS: In a retrospective, five-year (September 2007-September
      2012) observational study, four automated triggers were used to detect
      anticoagulant-related adverse events: activated partial thromboplastin time
      (aPTT) > 100 seconds in patients on an unfractionated heparin (UFH) infusion,
      International Normalized Ratio (INR) > 4, anti-factor Xa (anti-FXa) >1.5U/mL for
      patients on enoxaparin, and the documented use of protamine. RESULTS: For the
      1,664 triggers evaluated, 12 were associated with the aPTT trigger, only 1 of
      which was preventable. Receiver operator characteristic curve analysis indicated
      that increasing the aPTT trigger > 140 seconds would optimize sensitivity and
      specificity. The INR trigger identified four outpatients with adverse events. No
      adverse events were associated with the anti-FXa trigger. The protamine trigger
      identified 12 adverse events and was associated with more severe events. Minimal
      overlap was found with protamine and aPTT triggers. CONCLUSION: Laboratory- and
      medication-based triggers can be effective monitoring tools for anticoagulants.
      For patients receiving a UFH infusion, an aPTT cutoff value of > 140 seconds is
      more precise. We also found that protamine use as a trigger adds value to a
      trigger-based anticoagulant monitoring system. Continued improvement in the logic
      algorithms associated with the EHR-based trigger tool will allow expanded use of
      this tool in a clinical manner.

PMID- 25977127
TI  - Enhancing the effectiveness of team debriefings in medical simulation: more best
      practices.
AB  - BACKGROUND: Teamwork is a vital component of optimal patient care. In both
      clinical settings and medical education, a variety of approaches are used for the
      development of teamwork skills. Yet, for team members to receive the full
      educational benefit of these experiential learning opportunities, postsimulation
      feedback regarding the team's performance must be incorporated. Debriefings are
      among the most widely used form of feedback regarding team performance. A team
      debriefing is a facilitated or guided dialogue that takes place between team
      members following an action period to review and reflect on team performance.
      Team members discuss their perceptions of what occurred, why it occurred, and how
      they can enhance their performance. Simulation debriefing allows for greater
      control and planning than are logistically feasible for on-the-job performance.
      It is also unique in that facilitators of simulation-based training are generally
      individuals external to the team, whereas debriefing on the job is commonly led
      by an internal team member or conducted without a specified facilitator.
      Consequently, there is greater opportunity for selecting and training
      facilitators for team simulation events. Thirteen Best Practices: The 13 best
      practices, extracted from existing training and debriefing research, are
      organized under three general categories: (1) preparing for debriefing, (2)
      facilitator responsibilities during debriefing, and (3) considerations for
      debriefing content. For each best practice, considerations and practical
      implications are provided to facilitate the implementation of the recommended
      practices. CONCLUSION: The 13 best practices presented in this article should
      help health care organizations by guiding team simulation administrators, self
      directed medical teams, and debriefing facilitators in the optimization of
      debriefing to support learning for all team members.

PMID- 25977128
TI  - Development and evaluation of an electronic health record-based best-practice
      discharge checklist for hospital patients.
AB  - BACKGROUND: Checklists may help reduce discharge errors; however, current paper
      checklists have limited functionality. In 2013 a best-practice discharge
      checklist using the electronic health record (EHR) was developed and evaluated at
      Stanford University Medical Center (Stanford, California) in a cluster randomized
      trial to evaluate its usage, user satisfaction, and impact on physicians' work
      flow. METHODS: The study was divided into four phases. RESULTS: In Phase I, on
      the survey (N = 76), most of the participants (54.0%) reported using memory to
      remember discharge tasks. On a 0-100 scale, perception of checklists as being
      useful was strong (mean, 66.4; standard deviation [SD], 21.2), as was interest in
      EHR checklists (64.5, 26.6). In Phase II, the checklist consisted of 15 tasks
      categorized by admission, hospitalization, and discharge-planning. In Phase III,
      the checklist was implemented as an EHR "smart-phrase" allowing for automatic
      insertion. In Phase IV, in a trial with 60 participating physicians, 23 EHR
      checklist users reported higher usage than 12 paper users (28.5 versus 7.67, p =
      .019), as well as higher checklist integration with work flow (22.6 versus 1.67,
      p = .014), usefulness of checklist (33.7 versus. 8.92, p = .041), discharge
      confidence (30.8 versus 5.00, p = .029), and discharge efficiency (25.5 versus
      6.67, p = .056). Increasing EHR checklist use was correlated with usefulness ( r
      = .85, p < .001), confidence (r = .81, p < .001), and efficiency (r = .87, p <
      .001). CONCLUSIONS: The EHR checklist reminded physicians to complete discharge
      tasks, improved confidence, and increased process efficiency. This is the first
      study to show that medicine residents use "memory" as the most common method for
      remembering discharge tasks. These data reinforce the need for a formalized tool,
      such as a checklist, that residents can rely on to complete important discharge
      tasks.

PMID- 25977129
TI  - Editorial: crawling before walking: beginning to understand how clinicians
      communicate and behave during interunit handoffs.

PMID- 25977130
TI  - Collaborating-or "Selling" Patients? A Conceptual Framework for Emergency
      Department-to-Inpatient Handoff Negotiations.

PMID- 25977131
TI  - Retrospective survival analysis of 237 consecutive patients with multiple
      pulmonary metastases from advanced renal cell carcinoma exclusively resected by a
      1318-nm laser.
AB  - OBJECTIVES: Despite the introduction of new target drugs to treat pulmonary
      metastatic renal cell carcinoma (mRCC), complete surgical resection still
      generates significantly longer survival. We analysed the survival outcome for
      patients with pulmonary mRCC after extended laser metastasectomy with up to 110
      metastases and systematic lymphadenectomy to assess the utility and value of
      laser resection in the respective patient groups even with high number of
      metastases. METHODS: Between 1996 and 2012, 237 patients (150 men, 87 women)
      underwent curative intended pulmonary laser metastasectomy of mRCC. A total of
      2996 metastases (range: 1-110) were resected. Kaplan-Meier analysis was performed
      to assess overall survival in all 237 patients and for sub-groups. Multivariate
      analysis of prognostic factors was performed using Cox regression models.
      RESULTS: Two hundred and eight patients with R0-resection (88%) had 5-year
      overall survival rate and median overall survival of 54% and 69 months,
      respectively, significantly better than 7% and 19 months in those with incomplete
      resections (log-rank P < 0.00001). A mean of 13 metastases per patient were
      resected. Five-year survival for patients with 1, 2-5, 6-9, 10-29 or 30-110
      metastases resected was 62, 59, 60, 43 and 40%, respectively. In multivariate Cox
      regression of all 237 patients, only completeness of resection (P < 0.0001) and
      number of metastases (P = 0.0029) were independent factors. CONCLUSIONS: If
      complete resection is achieved, laser resection can remove even high numbers of
      metastases with considerable and comparable long-term survival known from
      previous reports. This tissue-saving technique allows repeated resections in case
      of recurrence.

PMID- 25977132
TI  - Laparoscopic circular stapled longitudinal extramucosal pyloroplasty: an
      alternative technique for pyloric disruption.
AB  - OBJECTIVES: Oesophagectomy with gastric pull-up is the most common surgical
      procedure for oesophageal cancer. Pyloroplasty may be performed to facilitate
      stomach emptying, but its role is still controversial. When laparoscopic
      mobilization of the stomach is performed, conventional extramucosal pyloroplasty
      may be difficult to carry out; therefore, we describe a new technique for
      mechanical pyloric disruption. METHODS: We conceived the laparoscopic
      longitudinal extramucosal partial section of the anterior pyloric wall using a
      circular stapler. We performed it in 6 patients undergoing oesophagectomy for
      cancer, with the laparoscopic abdominal step before thoracotomy. RESULTS: The
      procedure was easy and safe and without intraoperative complications in all
      patients. Postoperative video-oesophagogram showed regular anastomosis and graft
      emptying. CONCLUSIONS: Our preliminary experience has led us to conclude that
      circular stapler longitudinal extramucosal pyloroplasty is an easy, safe and
      quick procedure that can be performed in laparoscopic surgery. Moreover, it seems
      to ensure a regular emptying of the graft as standard pyloroplasty does.

PMID- 25977133
TI  - Violence against young women attending primary care services in Spain: prevalence
      and health consequences.
AB  - BACKGROUND: There are a significant number of studies assessing the negative
      health consequences of violence against women. However, a limited number of
      studies analyse the health consequences of violence committed against young women
      by different types of aggressors. OBJECTIVES: The goal of this study is to assess
      the prevalence of interpersonal violence against young women in Spain and analyse
      its impact on the physical and mental health of the victims. METHODS: A total of
      1076 women aged 18-25 years attending Spanish primary care services were
      selected. We estimated the prevalence of interpersonal violence and compared the
      health data and demographic characteristics of abused and non-abused young women,
      multi-logistic regression models were fitted. The Wald test was used to assess
      whether there were differences in the negative health consequences of intimate
      partner (IPV) versus non-IPV. RESULTS: As many as 27.6% young women reported a
      history of abuse, of whom 42.7% had been assaulted by their partner, 41.1% by
      someone other than their partner and 16.2% both by their partner and another
      person. The distribution of social and demographic characteristics was similar
      for IPV and non-IPV victims. Young abused women were three times more likely to
      suffer psychological distress and have somatic complaints, and they were four
      times more likely to use medication as compared to non-abused women. CONCLUSION:
      Our results suggest that all forms of violence compromise young women's health
      seriously. Including patients' history of abuse in their health record may help
      make more informed clinical decisions and provide a more integrated care.

PMID- 25977134
TI  - Specific and non-specific symptoms of colorectal cancer and contact to general
      practice.
AB  - BACKGROUND: To improve survival rates for colorectal cancer, referral guidelines
      have been implemented. First step in the diagnostic process is for the individual
      to recognize the symptoms and contact his/her general practitioner (GP) for
      evaluation. OBJECTIVES: To determine (i) the prevalence of specific and non
      specific symptom experiences indicative of colorectal cancer, (ii) the proportion
      of subsequent contacts to GPs, (iii) to explore the possible differences in
      symptom experience and contact to GPs between age and sex. METHODS: A nationwide
      study of 100000 adults, aged 20 years and older, were randomly selected in the
      general population and invited to participate in an internet-based survey. Items
      regarding experience of specific and non-specific alarm symptoms of colorectal
      cancer within the preceding 4 weeks and contact to GP were included. RESULTS: A
      total of 49706 subjects completed the questionnaire. Abdominal pain was the most
      common specific alarm symptom (19.7%) and tiredness was the most common non
      specific symptom (49.8%). The experiences of symptoms were more common among
      women and more common in the youngest age groups for both sexes. The symptom
      leading to the highest proportion of GP contacts was rectal bleeding (33.8%).
      When experiencing any combination of two specific alarm symptoms, the proportion
      who contacted a GP was less than 50%. The combination of a non-specific and a
      specific alarm symptom gave rise to the highest proportion of GP contacts.
      CONCLUSION: Although specific and non-specific alarm symptoms of colorectal
      cancer are common in the general population, the proportion of GP contacts is
      low.

PMID- 25977135
TI  - Behavior change techniques in popular alcohol reduction apps: content analysis.
AB  - BACKGROUND: Mobile phone apps have the potential to reduce excessive alcohol
      consumption cost-effectively. Although hundreds of alcohol-related apps are
      available, there is little information about the behavior change techniques
      (BCTs) they contain, or the extent to which they are based on evidence or theory
      and how this relates to their popularity and user ratings. OBJECTIVE: Our aim was
      to assess the proportion of popular alcohol-related apps available in the United
      Kingdom that focus on alcohol reduction, identify the BCTs they contain, and
      explore whether BCTs or the mention of theory or evidence is associated with app
      popularity and user ratings. METHODS: We searched the iTunes and Google Play
      stores with the terms "alcohol" and "drink", and the first 800 results were
      classified into alcohol reduction, entertainment, or blood alcohol content
      measurement. Of those classified as alcohol reduction, all free apps and the top
      10 paid apps were coded for BCTs and for reference to evidence or theory.
      Measures of popularity and user ratings were extracted. RESULTS: Of the 800 apps
      identified, 662 were unique. Of these, 13.7% (91/662) were classified as alcohol
      reduction (95% CI 11.3-16.6), 53.9% (357/662) entertainment (95% CI 50.1-57.7),
      18.9% (125/662) blood alcohol content measurement (95% CI 16.1-22.0) and 13.4%
      (89/662) other (95% CI 11.1-16.3). The 51 free alcohol reduction apps and the top
      10 paid apps contained a mean of 3.6 BCTs (SD 3.4), with approximately 12% (7/61)
      not including any BCTs. The BCTs used most often were "facilitate self-recording"
      (54%, 33/61), "provide information on consequences of excessive alcohol use and
      drinking cessation" (43%, 26/61), "provide feedback on performance" (41%, 25/61),
      "give options for additional and later support" (25%, 15/61) and "offer/direct
      towards appropriate written materials" (23%, 14/61). These apps also rarely
      included any of the 22 BCTs frequently used in other health behavior change
      interventions (mean 2.46, SD 2.06). Evidence was mentioned by 16.4% of apps, and
      theory was not mentioned by any app. Multivariable regression showed that apps
      including advice on environmental restructuring were associated with lower user
      ratings (Beta=-46.61, P=.04, 95% CI -91.77 to -1.45) and that both the techniques
      of "advise on/facilitate the use of social support" (Beta=2549.21, P=.04, 95% CI
      96.75-5001.67) and the mention of evidence (Beta=1376.74, P=.02, 95%, CI 208.62
      2544.86) were associated with the popularity of the app. CONCLUSIONS: Only a
      minority of alcohol-related apps promoted health while the majority implicitly or
      explicitly promoted the use of alcohol. Alcohol-related apps that promoted health
      contained few BCTs and none referred to theory. The mention of evidence was
      associated with more popular apps, but popularity and user ratings were only
      weakly associated with the BCT content.

PMID- 25977136
TI  - [Perceptions and experiences of access to health services and their utilization
      among the immigrant population].
AB  - OBJECTIVE: To identify and describe the needs and problems of the immigrant
      population related to access and utilization of health services. METHOD: A
      descriptive, qualitative, phenomenological study was conducted using focus
      groups. The study area was the county of Campo de Gibraltar (Spain), which
      represents the gateway to Europe for immigration from Africa. The final sample
      size (51 immigrants from 11 countries) was determined by theoretical saturation.
      A narrative analysis was conducted with QSR NVivo9 software. RESULTS: Immigrants'
      discourse showed four categories of analysis: response to a health problem,
      system access, knowledge of social and health resources, and health literacy
      needs. Responses to health problems and the route of access to the health care
      system differed according to some sociodemographic characteristics
      (nationality/culture of origin, length of residence, and economic status). In
      general, immigrants primarily used emergency services, hampering health promotion
      and prevention. The health literacy needs identified concerned language
      proficiency and the functioning of the health system. CONCLUSIONS: There is a
      need to promote interventions to enhance health literacy among immigrants. These
      interventions should take into account diversity and length of residence, and
      should be based on an action-participation methodology.

PMID- 25977137
TI  - ICSH guidelines for the standardization of bone marrow immunohistochemistry.
AB  - Bone marrow (BM) tissue biopsy evaluation, including trephine biopsy and clot
      section, is an integral part of BM investigation and is often followed by
      ancillary studies, in particular immunohistochemistry (IHC). IHC provides in situ
      coupling of morphological assessment and immunophenotype. The number of different
      IHC tests that can be applied to BM trephine biopsies and the number of
      indications for IHC testing is increasing concurrently with the development of
      flow cytometry and molecular diagnostic methods. An international Working Party
      for the Standardization of Bone Marrow IHC was formed by the International
      Council for Standardization in Hematology (ICSH) to prepare a set of guidelines
      for the standardization of BM IHC based on currently available published evidence
      and modern understanding of quality assurance principles as applied to IHC in
      general. The guidelines were discussed at the ICSH General Assemblies and
      reviewed by an international panel of experts to achieve further consensus and
      represent further development of the previously published ICSH guidelines for the
      standardization of BM specimens handling and reports.

PMID- 25977138
TI  - Feasibility of measuring thermoregulation during RF heating of the human calf
      muscle using MR based methods.
AB  - PURPOSE: One of the main safety concerns in MR is heating of the subject due to
      radiofrequency (RF) exposure. Recently was shown that local peak temperatures can
      reach dangerous values and the most prominent parameter for accurate temperature
      estimations is thermoregulation. Therefore, the goal of this research is testing
      the feasibility of measuring thermoregulation in vivo using MR methods. THEORY
      AND METHODS: The calves of 13 volunteers were scanned at 3 tesla. A Proton
      Resonance Frequency Shift method was used for temperature measurement. Arterial
      Spin Labeling and phase contrast scans were used for perfusion and flow
      measurements respectively. The calves were monitored during extreme RF exposure
      (20 W/kg, 16 min) and after physical exercise. RESULTS: Temperature increases due
      to RF absorption (range of the 90th percentile of all volunteers: 1.1-2.5 degrees
      C) matched with the reference skin temperature changes. Increases in perfusion
      and flow were defined on the whole leg and normalized to baseline. Perfusion
      showed a significant increase due to RF heating (ratio compared with baseline:
      1.28 +/- 0.37; P < 0.05), the influence of exercise was much greater, however
      (2.97 +/- 2.45, P < 0.01). CONCLUSION: This study represents a first exploration
      of measuring thermoregulation, which will become essential when new safety
      guidelines are based on thermal dose.

PMID- 25977139
TI  - A Case of Leprosy: Not as Rare as One Might Expect.

PMID- 25977140
TI  - Anti-Candida Activity of New Azole Derivatives Alone and in Combination with
      Fluconazole.
AB  - The rate of Candida spp. infection is increasing, and resistance to azole
      antifungals is becoming increasingly common. Therefore, there is a need for
      discovery of new antifungal agents and for development of new modes of treatment
      using existing agents. In this in vitro study, the antifungal activity of two new
      imidazole derivatives was tested against a set of 20 Candida isolates, which
      included five different species. Treatment was carried out with the compound
      alone and in combination with fluconazole. Overall, we found that one of the new
      compounds, 31, was similar to fluconazole (FLC) in its efficacy against the
      Candida isolates and that compound 42 was superior to FLC. Furthermore, when
      combined with FLC, both compounds showed synergistic effects against 17 of the 20
      tested isolates. No antagonistic interactions were observed. This study shows
      that our two new imidazole-derived compounds have good potential as general
      treatments for Candida infection and as a means to improve the current treatments
      with FLC.

PMID- 25977141
TI  - [Lactational breast abscesses: Do we still need surgery?].
AB  - AIM: To show the effectiveness of ultrasound-guided puncture in the treatment of
      lactational breast abscess and identify its risk factors. MATERIALS AND METHODS:
      Retrospective descriptive study at the CHU of Lyon-Sud from December 2007 to
      December 2013, including patients with lactational breast abscess confirmed on
      ultrasound and treated with antibiotics and analgesics. Realisation of ultrasound
      guided needle under local anesthesia by the radiologist and washing the cavity
      with physiological serum. RESULTS: Forty patients had lactational abscesses at an
      average of 10 weeks post-partum. Thirty-four patients were treated by needle
      aspiration, of which 2 had first surgical drainage. The average size of the
      abscess was 41.2mm. The success rate of needle aspiration was 91.2%. No cases of
      recurrence were observed, however, there were 5 fistulisations. In all, 91.2%
      were treated on an outpatient basis. In 87.8% of cases, breastfeeding was
      continued on the healthy side and in 48.5% of cases on the affected side. The
      major risk factor for abscess was mastitis in 91.1% of cases. CONCLUSION:
      Ultrasound guidance of needle aspiration should be gold standard for the
      treatment of lactational breast abscesses to continue breastfeeding including the
      affected side.

PMID- 25977142
TI  - Evolutionary origin and demographic history of an ancient conifer (Juniperus
      microsperma) in the Qinghai-Tibetan Plateau.
AB  - All Qinghai-Tibetan Plateau (QTP) endemic species are assumed to have originated
      recently, although very rare species most likely diverged early. These ancient
      species provide an excellent model to examine the origin and evolution of QTP
      endemic plants in response to the QTP uplifts and the climate changes that
      followed in this high altitude region. In this study, we examined these
      hypotheses by employing sequence variation from multiple nuclear and chloroplast
      DNA of 239 individuals of Juniperus microsperma and its five congeners. Both
      phylogenetic and population genetic analyses revealed that J. microsperma
      diverged from its sister clade comprising two species with long isolation around
      the Early Miocene, which corresponds to early QTP uplift. Demographic modeling
      and coalescent tests suggest that J. microsperma experienced an obvious
      bottleneck event during the Quaternary when the global climate greatly
      oscillated. The results presented here support the hypotheses that the QTP
      uplifts and Quaternary climate changes played important roles in shaping the
      evolutionary history of this rare juniper. 

PMID- 25977143
TI  - Impact of Land Use Management and Soil Properties on Denitrifier Communities of
      Namibian Savannas.
AB  - We studied potential denitrification activity and the underlying denitrifier
      communities in soils from a semiarid savanna ecosystem of the Kavango region in
      NE Namibia to help in predicting future changes in N(2)O emissions due to
      continuing changes of land use in this region. Soil type and land use (pristine,
      fallow, and cultivated soils) influenced physicochemical characteristics of the
      soils that are relevant to denitrification activity and N(2)O fluxes from soils
      and affected potential denitrification activity. Potential denitrification
      activity was assessed by using the denitrifier enzyme activity (DEA) assay as a
      proxy for denitrification activity in the soil. Soil type and land use influenced
      C and N contents of the soils. Pristine soils that had never been cultivated had
      a particularly high C content. Cultivation reduced soil C content and the
      abundance of denitrifiers and changed the composition of the denitrifier
      communities. DEA was strongly and positively correlated with soil C content and
      was higher in pristine than in fallow or recently cultivated soils. Soil type and
      the composition of both the nirK- and nirS-type denitrifier communities also
      influenced DEA. In contrast, other soil characteristics like N content, C:N
      ratio, and pH did not predict DEA. These findings suggest that due to greater
      availability of soil organic matter, and hence a more effective N cycling, the
      natural semiarid grasslands emit more N(2)O than managed lands in Namibia.

PMID- 25977145
TI  - Building a Human Health Risk Assessment Ontology (RsO): A Proposed Framework.
AB  - Over the last decade the health and environmental research communities have made
      significant progress in collecting and improving access to genomic, toxicology,
      exposure, health, and disease data useful to health risk assessment. One of the
      barriers to applying these growing volumes of information in fields such as risk
      assessment is the lack of informatics tools to organize, curate, and evaluate
      thousands of journal publications and hundreds of databases to provide new
      insights on relationships among exposure, hazard, and disease burden. Many fields
      are developing ontologies as a way of organizing and analyzing large amounts of
      complex information from multiple scientific disciplines. Ontologies include a
      vocabulary of terms and concepts with defined logical relationships to each
      other. Building from the recently published exposure ontology and other relevant
      health and environmental ontologies, this article proposes an ontology for health
      risk assessment (RsO) that provides a structural framework for organizing risk
      assessment information and methods. The RsO is anchored by eight major concepts
      that were either identified by exploratory curations of the risk literature or
      the exposure-ontology working group as key for describing the risk assessment
      domain. These concepts are: (1) stressor, (2) receptor, (3) outcome, (4) exposure
      event, (5) dose-response approach, (6) dose-response metric, (7) uncertainty, and
      (8) measure of risk. We illustrate the utility of these concepts for the RsO with
      example curations of published risk assessments for ionizing radiation, arsenic
      in drinking water, and persistent pollutants in salmon. 

PMID- 25977144
TI  - [Cost-effectiveness analysis of universal screening for thyroid disease in
      pregnant women in Spain].
AB  - OBJECTIVE: To assess the cost-effectiveness of universal screening for thyroid
      disease in pregnant women in Spain as compared to high risk screening and no
      screening. METHODOLOGY: A decision-analytic model comparing the incremental cost
      per quality-adjusted life year (QALY) of universal screening versus high risk
      screening and versus no screening. was used for the pregnancy and postpartum
      period. Probabilities from randomized controlled trials were considered for
      adverse obstetrical outcomes. A Markov model was used to assess the lifetime
      period after the first postpartum year and account for development of overt
      hypothyroidism. The main assumptions in the model and use of resources were
      assessed by local clinical experts. The analysis considered direct healthcare
      costs only. RESULTS: Universal screening gained .011 QALYs over high risk
      screening and .014 QALYS over no screening. Total direct costs per patient were
      ?5,786 for universal screening, ?5,791 for high risk screening, and ?5,781 for no
      screening. Universal screening was dominant compared to risk-based screening and
      a very cost-effective alternative as compared to no screening. Use of universal
      screening instead of high risk screening would result in ?2,653,854 annual
      savings for the Spanish National Health System. CONCLUSIONS: Universal screening
      for thyroid disease in pregnant women in the first trimester is dominant in Spain
      as compared to risk-based screening, and is cost-effective as compared to no
      screening (incremental cost-effectiveness ratio of ?374 per QALY). Moreover, it
      allows diagnosing and treating cases of clinical and subclinical hypothyroidism
      that may not be detected when only high-risk women are screened.

PMID- 25977147
TI  - Remission of splenic marginal zone lymphoma in a patient treated for hepatitis B:
      a case of HBV-associated lymphoma.
AB  - Splenomegaly is a common finding in chronic hepatitis B infection. We present the
      case of a man with an acute flare of chronic hepatitis B infection, where
      splenomegaly in absence of portal hypertension led to the diagnosis of splenic
      marginal zone lymphoma (SMZL) with bone marrow involvement. Adequate suppression
      of the hepatitis B virus (HBV) viral load with tenofovir resulted in complete
      remission of the lymphoma. 

PMID- 25977146
TI  - Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by
      meticillin resistant Staphylococcus aureus: randomised controlled trial.
AB  - OBJECTIVE: To show non-inferiority of trimethoprim-sulfamethoxazole compared with
      vancomycin for the treatment of severe infections due to meticillin resistant
      Staphylococcus aureus (MRSA). DESIGN: Parallel, open label, randomised controlled
      trial. SETTING: Four acute care hospitals in Israel. PARTICIPANTS: Adults with
      severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and
      vancomycin. Patients with left sided endocarditis, meningitis, chronic
      haemodialysis, and prolonged neutropenia were excluded. INTERVENTIONS:
      Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g
      twice daily for a minimum of seven days and then by indication. MAIN OUTCOME
      MEASURES: The primary efficacy outcome was treatment failure assessed at day 7,
      consisting of death, persistence of haemodynamic instability or fever, stable or
      worsening Sequential Organ Failure Assessment score, and persistence of
      bacteraemia. The primary safety outcome was all cause mortality at day 30. Non
      inferiority was defined by a difference of less than 15% for treatment failure.
      RESULTS: 252 patients were included in the trial, of whom 91 (36%) had
      bacteraemia. No significant difference in treatment failure was seen for
      trimethoprim-sulfamethoxazole (51/135, 38%) versus vancomycin (32/117, 27%)-risk
      ratio 1.38 (95% confidence interval 0.96 to 1.99). However, trimethoprim
      sulfamethoxazole did not meet the non-inferiority criterion-absolute difference
      10.4% (95% confidence interval -1.2% to 21.5%). For patients with bacteraemia,
      the risk ratio was 1.40 (0.91 to 2.16). In a multivariable logistic regression
      analysis, trimethoprim-sulfamethoxazole was significantly associated with
      treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality
      rate was 32/252 (13%), with no significant difference between arms. Among
      patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole
      and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93). CONCLUSIONS:
      High dose trimethoprim-sulfamethoxazole did not achieve non-inferiority to
      vancomycin in the treatment of severe MRSA infections. The difference was
      particularly marked for patients with bacteraemia. Trial registration Clinical
      trials NCT00427076.

PMID- 25977149
TI  - Prognostic factors for low rectal cancer patients undergoing intersphincteric
      resection after neoadjuvant chemoradiation.
AB  - OBJECTIVES: This study aimed to investigate prognostic factors for low rectal
      cancer patients undergoing intersphincteric resection (ISR) following neoadjuvant
      chemoradiation (CRT). METHODS: We retrospectively reviewed 163 primary rectal
      cancer patients without distant metastasis who underwent ISR following
      neoadjuvant CRT between January 2006 and December 2011. Prognostic factors for
      disease-free survival (DFS) and local recurrence-free survival (LRFS) were
      evaluated. RESULTS: The median follow-up period was 53 months (range, 0-82
      months). Kaplan-Meier survival analysis indicated different 3-year DFS (stage 0,
      96.2%; I, 84.8%; II, 72.9%; III, 38.0%) and 3-year LRFS (stage 0, 100.0%; I,
      92.4%; II, 91.1%; III, 70.9%) according to pathologic TNM stages, particularly
      stage III. Multivariable Cox regression analysis suggested that DFS was
      associated with ypT (3/4 vs. 0/1/2) and ypN (1/2 vs. 0) stages, whereas LRFS with
      ypN stage (1/2 vs. 0), tumor size (>=3.5 cm vs. <3.5 cm), and tumor height from
      the anal verge (<=2 cm vs. >2 cm). CONCLUSIONS: ISR following CRT could be
      feasible in stage-I and II low rectal cancer patients, but might be related to
      poor oncologic outcomes in those with stage-III disease. The indication for ISR
      or abdominoperineal resection should be carefully evaluated in cases of low
      rectal cancer with suspicious lymph node metastasis after CRT.

PMID- 25977148
TI  - Association of Interleukin-10 -3575T>A and -1082A>G polymorphisms with non
      Hodgkin lymphoma susceptibility: a comprehensive review and meta-analysis.
AB  - A number of studies have investigated the associations between IL-10
      polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility; however, the
      conclusions were still contradictory. To acquire a more precise estimation of the
      association, we performed the current meta-analysis. We systematically searched
      publications from EMBASE and MEDLINE, and calculated pooled odds ratios (ORs) and
      95 % confidence intervals (CIs) using either fixed-effects or random-effects
      model. Genotype-based IL-10 mRNA expression analysis was performed using online
      public database of 270 individuals with three different ethnicities. A total of
      10,703 cases and 11,823 controls from 10 studies were included for the -3575T>A
      polymorphism, 10,226 cases and 12,215 controls from 17 studies for the -1082A>G
      polymorphism. Pooled results indicated that IL-10 -3575T>A was associated with
      increased risk of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma
      (FL), especially for Caucasians and hospital-based population. There was no
      association between IL-10 -1082A>G and NHL risk. However, subgroup analysis
      showed that IL-10 -1082GG might confer increased susceptibility to FL. In
      summary, this meta-analysis indicated that -3575T>A polymorphism was associated
      with altered NHL susceptibility for Caucasians and hospital-based population,
      especially for DLBCL and FL subtypes. The -1082A>G polymorphism may contribute to
      increased FL risk. Further large-scale population studies among different
      ethnicities are needed to validate these results. 

PMID- 25977150
TI  - Closed Medial Malleolar Multifragment Fracture With a Posterior Tibialis Tendon
      Rupture: A Case Report and Review of the Literature.
AB  - Ankle fractures represent an exciting field of traumatology because of the wide
      variety of clinical presentations, injury mechanisms, and treatment options.
      Rupture of the posterior tibialis tendon (PTT) with ankle fracture can occur
      during trauma that involves pronation and external rotation of the foot or, less
      commonly, secondary to direct trauma to the ankle. This tendon injury is uncommon
      and probably misdiagnosed in many cases, because of the difficult clinical
      examination secondary to the pain and swelling. The identification and early
      treatment of PTT tears is essential for good functional outcomes to prevent the
      main mid- to long-term complication of disabling acquired flatfoot due to tendon
      failure. In the present report, we provide a review of the published data
      regarding ankle fractures associated with PTT rupture and describe our experience
      with a case of a multifragment medial malleolus fracture and complete rupture of
      the PTT diagnosed intraoperatively and surgically treated in a 34-year-old male,
      with 2.5 years of follow-up. 

PMID- 25977151
TI  - Tibialis Anterior Tendon Lengthening: Adjunctive Treatment of Plantar Lateral
      Column Diabetic Foot Ulcers.
AB  - Tendon lengthening and rebalancing are adjunctive procedures for the treatment of
      chronic ulcerations in the diabetic foot. For example, the equinus deformity has
      been implicated as a major deforming force and is surgically treated by
      lengthening the Achilles tendon. A contracted tibialis anterior tendon can also
      play a role by potentiating a varus rotational force, increasing the pressures
      along the lateral column of the forefoot, and resulting in the development or
      chronicity of an ulceration. We present a novel application of tibialis anterior
      tendon lengthening for the adjunctive treatment of chronic ulcerations in the
      diabetic foot. 

PMID- 25977152
TI  - Epidemiology of High-Heel Shoe Injuries in U.S. Women: 2002 to 2012.
AB  - The purpose of the present study was to investigate the epidemiology of high-heel
      related injuries among a nationally representative population of women in the
      United States and to analyze the demographic differences within this group. The
      data used in the present study were collected from the Consumer Product Safety
      Commission's National Electronic Injury Surveillance System. A total of 3294
      injuries, representing an estimated 123,355 high-heel-related injuries, were
      treated in emergency departments within the United States from 2002 to 2012. The
      overall rate of high-heel-related injuries for the study was 7.32 per 100,000
      females (95% confidence interval 7.08 to 7.56). The injury rate was greatest for
      young adult females, with the greatest rates observed for those aged 20 to 29
      years (18.38 per 100,000 females) and those aged 30 to 39 years (11.07 per
      100,000 females). The results from the present study suggest that high-heel
      related injuries have nearly doubled during the 11-year period from 2002 to 2012.
      Injuries from high heels are differential by body region, with most injuries
      occurring as sprains and strains to the foot and ankle. Although high heels might
      be stylish, from a health standpoint, it could be worthwhile for females and
      those interested in wearing high heels to understand the risks of wearing high
      heeled shoes and the potential harm that precarious activities in high-heeled
      shoes can cause. The results of the present study can be used in the development
      of a prospective cohort study to investigate the risk of injury from high-heeled
      shoes, accounting for the exposure time and studying differences in demographics
      (e.g., age and race).

PMID- 25977153
TI  - Assessing Diagnostic Tests II: Grading on a Curve.
AB  - In this Investigators' Corner, I continue discussing how to introduce and assess
      new diagnostic tests to replace older tests that are considered gold standards.
      Specifically, I talk about how to assess a "family" of diagnostics, and how to
      choose an optimal "family member." 

PMID- 25977154
TI  - Landmark constrained genus-one surface Teichmuller map applied to surface
      registration in medical imaging.
AB  - We address the registration problem of genus-one surfaces (such as vertebrae
      bones) with prescribed landmark constraints. The high-genus topology of the
      surfaces makes it challenging to obtain a unique and bijective surface mapping
      that matches landmarks consistently. This work proposes to tackle this
      registration problem using a special class of quasi-conformal maps called
      Teichmuller maps (T-Maps). A landmark constrained T-Map is the unique mapping
      between genus-1 surfaces that minimizes the maximal conformality distortion while
      matching the prescribed feature landmarks. Existence and uniqueness of the
      landmark constrained T-Map are theoretically guaranteed. This work presents an
      iterative algorithm to compute the T-Map. The main idea is to represent the set
      of diffeomorphism using the Beltrami coefficients (BC). The BC is iteratively
      adjusted to an optimal one, which corresponds to our desired T-Map that matches
      the prescribed landmarks and satisfies the periodic boundary condition on the
      universal covering space. Numerical experiments demonstrate the effectiveness of
      our proposed algorithm. The method has also been applied to register vertebrae
      bones with prescribed landmark points and curves, which gives accurate surface
      registrations. 

PMID- 25977155
TI  - Cell-sensitive phase contrast microscopy imaging by multiple exposures.
AB  - We propose a novel way of imaging live cells in a Petri dish by the phase
      contrast microscope. By taking multiple exposures of phase contrast microscopy
      images on the same cell dish, we estimate a cell-sensitive camera response
      function which responds to cells' irradiance signals but generates a constant on
      non-cell background signal. The result of this new microscopy imaging is visually
      superior quality, which reveals the appearance details of cells and suppresses
      background noise near zero. Using the cell-sensitive microscopy imaging, cells'
      original irradiance signals are restored from all exposures and the irradiance
      signals on non-cell background regions are restored as a uniform constant (i.e.,
      the imaging system is sensitive to cells only but insensitive to non-cell
      background). The restored irradiance signals greatly facilitate the cell
      segmentation by simple thresholding. The experimental results validate that high
      quality cell segmentation can be achieved by our approach. 

PMID- 25977156
TI  - Automatic multi-resolution shape modeling of multi-organ structures.
AB  - Point Distribution Models (PDM) are among the most popular shape description
      techniques and their usefulness has been demonstrated in a wide variety of
      medical imaging applications. However, to adequately characterize the underlying
      modeled population it is essential to have a representative number of training
      samples, which is not always possible. This problem is especially relevant as the
      complexity of the modeled structure increases, being the modeling of ensembles of
      multiple 3D organs one of the most challenging cases. In this paper, we introduce
      a new GEneralized Multi-resolution PDM (GEM-PDM) in the context of multi-organ
      analysis able to efficiently characterize the different inter-object relations,
      as well as the particular locality of each object separately. Importantly, unlike
      previous approaches, the configuration of the algorithm is automated thanks to a
      new agglomerative landmark clustering method proposed here, which equally allows
      us to identify smaller anatomically significant regions within organs. The
      significant advantage of the GEM-PDM method over two previous approaches (PDM and
      hierarchical PDM) in terms of shape modeling accuracy and robustness to noise,
      has been successfully verified for two different databases of sets of multiple
      organs: six subcortical brain structures, and seven abdominal organs. Finally, we
      propose the integration of the new shape modeling framework into an active shape
      model-based segmentation algorithm. The resulting algorithm, named GEMA, provides
      a better overall performance than the two classical approaches tested, ASM, and
      hierarchical ASM, when applied to the segmentation of 3D brain MRI. 

PMID- 25977158
TI  - Reconstructing cerebrovascular networks under local physiological constraints by
      integer programming.
AB  - We introduce a probabilistic approach to vessel network extraction that enforces
      physiological constraints on the vessel structure. The method accounts for both
      image evidence and geometric relationships between vessels by solving an integer
      program, which is shown to yield the maximum a posteriori (MAP) estimate to a
      probabilistic model. Starting from an overconnected network, it is pruning vessel
      stumps and spurious connections by evaluating the local geometry and the global
      connectivity of the graph. We utilize a high-resolution micro computed tomography
      (MUCT) dataset of a cerebrovascular corrosion cast to obtain a reference network
      and learn the prior distributions of our probabilistic model and we perform
      experiments on in-vivo magnetic resonance microangiography (MUMRA) images of
      mouse brains. We finally discuss properties of the networks obtained under
      different tracking and pruning approaches. 

PMID- 25977157
TI  - Automatic segmentation of occluded vasculature via pulsatile motion analysis in
      endoscopic robot-assisted partial nephrectomy video.
AB  - Hilar dissection is an important and delicate stage in partial nephrectomy,
      during which surgeons remove connective tissue surrounding renal vasculature.
      Serious complications arise when the occluded blood vessels, concealed by fat,
      are missed in the endoscopic view and as a result are not appropriately clamped.
      Such complications may include catastrophic blood loss from internal bleeding and
      associated occlusion of the surgical view during the excision of the cancerous
      mass (due to heavy bleeding), both of which may compromise the visibility of
      surgical margins or even result in a conversion from a minimally invasive to an
      open intervention. To aid in vessel discovery, we propose a novel automatic
      method to segment occluded vasculature from labeling minute pulsatile motion that
      is otherwise imperceptible with the naked eye. Our segmentation technique
      extracts subtle tissue motions using a technique adapted from phase-based video
      magnification, in which we measure motion from periodic changes in local phase
      information albeit for labeling rather than magnification. Based on measuring
      local phase through spatial decomposition of each frame of the endoscopic video
      using complex wavelet pairs, our approach assigns segmentation labels by
      detecting regions exhibiting temporal local phase changes matching the heart
      rate. We demonstrate how our technique is a practical solution for time-critical
      surgical applications by presenting quantitative and qualitative performance
      evaluations of our vessel detection algorithms with a retrospective study of
      fifteen clinical robot-assisted partial nephrectomies. 

PMID- 25977159
TI  - Statistically-driven 3D fiber reconstruction and denoising from multi-slice
      cardiac DTI using a Markov random field model.
AB  - The construction of subject-specific dense and realistic 3D meshes of the
      myocardial fibers is an important pre-requisite for the simulation of cardiac
      electrophysiology and mechanics. Current diffusion tensor imaging (DTI)
      techniques, however, provide only a sparse sampling of the 3D cardiac anatomy
      based on a limited number of 2D image slices. Moreover, heart motion affects the
      diffusion measurements, thus resulting in a significant amount of noisy fibers.
      This paper presents a Markov random field (MRF) approach for dense reconstruction
      of 3D cardiac fiber orientations from sparse DTI 2D slices. In the proposed MRF
      model, statistical constraints are used to relate the missing and the known
      fibers, while a consistency term is encoded to ensure that the obtained 3D meshes
      are locally continuous. The validation of the method using both synthetic and
      real DTI datasets demonstrates robust fiber reconstruction and denoising, as well
      as physiologically meaningful estimations of cardiac electrical activation. 

PMID- 25977160
TI  - Pseudovibrio hongkongensis sp. nov., isolated from a marine flatworm.
AB  - A Gram-negative, motile, rod-shaped bacterial strain, designated UST20140214
      015B(T), was isolated from a marine flatworm (Polyclad). The bacterium was found
      to be Gram-negative, oxidase and catalase positive, long-rod shaped, and motile
      by means of several peritrichous or subpolar flagella. Strain UST20140214-015B(T)
      grew optimally at 28  degrees C, at pH 7.0 and in the presence of 3 % (w/v) NaCl.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain
      UST20140214-015B(T) belongs to the genus Pseudovibrio, with highest sequence
      similarity to Pseudovibrio japonicus WSF2(T) (96.9 %), followed by P.
      ascidiaceicola F423(T) (96.7 %), P. denitrificans DN34(T) (96.6 %), P. axinellae
      Ad2(T) (96.3 %). All the other species shared <95.5 % sequence similarity. The
      principal fatty acids were identified as summed feature 8 (C18:1 omega7c/omega6c,
      as defined by the MIDI system; 70.8 %), C16:0 (9.1 %), summed feature 3 (C16:1
      omega6c/C16:1 omega7c; 5.7 %). The G+C content of the chromosomal DNA was
      determined to be 53.3 mol%. The combined genotypic and phenotypic data show that
      strain UST20140214-015B(T) represents a novel species within the genus
      Pseudovibrio, for which the name Pseudovibrio hongkongensis sp. nov. is proposed,
      with the type strain UST20140214-015B(T) (=KCTC 42383(T) = MCCC 1K00451(T)).

PMID- 25977162
TI  - Letter to the Editors.

PMID- 25977161
TI  - Bacteremic meningitis caused by Parvimonas micra in an immunocompetent host.
AB  - A 61-year-old man with chronic hepatitis B and dyslipidemia visited the emergency
      department with a fever and severe headache. He was diagnosed with bacterial
      meningitis after a lumbar puncture, and blood culture revealed Parvimonas micra
      bacteremia. Although he had a history of extraction of a molar two weeks before
      symptom onset, there was no evidence of abscess formation on physical examination
      or imaging studies. He was successfully treated with oral metronidazole for 12
      days after 9 days of treatment with IV ceftriaxone and vancomcycin. This is the
      first report of primary bacterial meningitis caused by this organism, which
      indicates that this organism is capable of being a bacterial meningitis pathogen.

PMID- 25977163
TI  - Myocardial deformation imaging unmasks subtle left ventricular systolic
      dysfunction in asymptomatic and treatment-naive HIV patients.
AB  - BACKGROUND: Patients infected by the human immunodeficiency virus (HIV) and
      receiving highly active antiretroviral therapy have a higher incidence of
      cardiovascular disease than healthy subjects, but little is known about cardiac
      function in asymptomatic and treatment-naive patients. We sought to study cardiac
      function in asymptomatic HIV-infected, treatment-naive patients. METHODS: We
      studied 41 HIV-infected and treatment-naive patients and 20 age- and sex-matched
      healthy controls. Patients with cardiac symptoms, history of cardiac disease or
      NT-proBNP >100 pg/mL were excluded. We addressed cardiac function using standard
      echocardiography along with tissue Doppler (TDI) measurements, including
      strain/strain rate assessment. RESULTS: Standard echocardiographic parameters did
      not differ between groups, except for transmitral E wave velocity (64.8 +/- 14
      cm/s in HIV vs 76.1 +/- 10 cm/s in controls, p = 0.002). In contrast, TDI mitral
      and tricuspid annulus s velocity and all strain/strain rate measurements were
      significantly lower in HIV patients: s lateral, 10.2 +/- 2.4/11.3 +/- 0.7, p =
      0.011; s septal, 8.1 +/- 1.6/8.7 +/- 0.8, p = 0.045; s tricuspid, 13.4 +/-
      2.3/14.9 +/- 1.3, p = 0.002; strain/strain rate, septal (strain/strain rate, 15.1
      +/- 5.7/-0.9 +/- 0.3, 25.3 +/- 1.7/-1.9 +/- 0.2, p < 0.001), anterior (16.7 +/-
      3/-1.0 +/- 0.1, 26.7 +/- 1.7/-1.9 +/- 0.2, p < 0.001), lateral (16.0 +/- 6/-1.0
      +/- 0.1, 27.5 +/- 1.8/-2.2 +/- 0.3, p < 0.001) and posterior (15.2 +/- 5.8/-1.0
      +/- 0.2, 26.2 +/- 1.8/-2.2 +/- 0.3, p < 0.001) left ventricular wall.
      CONCLUSIONS: HIV infection itself is accompanied by subclinical systolic
      dysfunction, not apparent to standard echocardiography that can be unmasked
      though using sensitive echocardiographic techniques.

PMID- 25977164
TI  - Expression of genes involved in immune response and in vitro immunosuppressive
      effect of equine MSCs.
AB  - The immunomodulatory capacities of mesenchymal stem cells (MSCs) have made them
      the subject of increased clinical interest for tissue regeneration and repair. We
      have studied the immunomodulatory capacity of equine MSCs derived from bone
      marrow (BM-MSCs) and adipose tissue (AT-MSCs) in cocultures with allogeneic
      peripheral blood mononuclear cells (PBMCs). Different isoforms and concentrations
      of phytohaemaglutinin (PHA) were tested to determine the best stimulation
      conditions for PBMC proliferation and a proliferation assay was performed for 7
      days to determine the optimal day of stimulation of PBMCs. The effect of the dose
      and source of MSCs was evaluated in cocultures of 10(5) PBMCs with different
      ratios of AT- and BM-MSCs (1:1, 1:10, 1:20 and 1:50). Proliferation rates of the
      PBMCs were evaluated using BrdU ELISA colorimetric assay. PHA stimulated equine
      PBMCs reached their peak of growth after 3 days of culture. The immunoassay
      showed a decrease of the PBMCs growth at high ratio cocultures (1:1 and 1:10).
      Equine BM-MSCs and AT-MSCs demonstrated an ability to suppress the proliferation
      of stimulated PBMCs. Although MSCs derived from both sources displayed
      immunosuppressive effects, AT-MSCs were slightly more potent than BM-MSCs. In
      addition, the expression of 26 genes coding for different molecules implicated in
      the immune response was analyzed in cocultures of BM-MSCs and PHA stimulated
      PBMSCs by reverse transcriptase real time quantitative PCR (RT-qPCR). An
      upregulation in genes associated with the production of interleukins and
      cytokines such as TNF-alpha and TGF-beta1 was observed except for IFN-gamma whose
      expression significantly decreased. The variations of interleukins and cytokine
      receptors showed no clear patterns. COX-1 and COX-2 showed similar expression
      patterns while INOs expression significantly decreased in the two cell types
      present in the coculture. Cyclin D2 and IDO-1 showed an increased expression and
      CD90, ITG-beta1 and CD44 expression decreased significantly in BM-MSCs cocultured
      with PHA stimulated PBMCs. On the contrary, CD6 and VCAM1 expression increased in
      these cells. With regard to the expression of the five genes involved in antigen
      presentation, an upregulation was observed in both cocultured MSCs and stimulated
      PBMCs. This study contributes to the knowledge of the immunoregulatory properties
      of equine MSCs, which are notably important for the treatment of inflammation
      processes, such as tendinitis and osteoarthritis. 

PMID- 25977165
TI  - Corporal Punishment: Evaluation of an Intervention by PNPs.
AB  - INTRODUCTION: Corporal punishment (CP) is defined as the use of physical force
      with the intention of causing a child to experience pain but not injury for the
      purpose of correction or control of the child's behavior. CP has been linked to a
      variety of negative consequences for children, including physical abuse,
      eternalizing behavioral problems, and slowed cognitive development. Many American
      children continue to experience CP at the hands of their parents and other
      caregivers. The purpose of this study was to evaluate learner attitude toward CP
      before and after implementation of a pediatric nurse practitioner-designed
      educational intervention and influences upon learner attitude and beliefs about
      CP. METHOD: This study used a pre- and postsurvey design to assess learner
      attitude about CP before and after participation in an educational intervention.
      Influences upon learner attitudes and beliefs regarding CP were also described.
      Learners (N = 882) were health care providers. RESULTS: Nearly all learners (n =
      747; 84.7%) stated that the way their parents disciplined them influenced their
      attitudes toward CP. Fewer than one fifth of learners who were also parents (n =
      126; 14.4%) reported that their child's health care provider had ever discussed
      child discipline with them. Prior to the educational intervention, more than one
      third of learners (n = 351; 39.88%) endorsed spanking as sometimes necessary, yet
      significantly fewer learners (n = 251; 28.9%; p < .001) made this statement after
      the educational intervention. Child discipline management was included in the
      health care provider education for fewer than half of learners (n = 365; 41.4%).
      DISCUSSION: The potential for experiencing CP as a child to result in negative
      consequences for children has been well documented, yet many American parents
      continue to use CP as a form of child discipline, and some pediatric health care
      professionals continue to endorse its use. Pediatric health care providers,
      including nurses and pediatric nurse practitioners, need to be educated about
      child discipline and CP. All pediatric health care providers need to advocate for
      the use of positive parenting principles and discourage the use of CP.

PMID- 25977166
TI  - Sodium intake combining cholinergic activation and noradrenaline into the lateral
      parabrachial nucleus.
AB  - The administration of cholinergic agonists like pilocarpine intraperitoneally
      (i.p.) or carbachol intracerebroventricularly (i.c.v.) induces water, but non
      significant hypertonic NaCl intake. These treatments also produce pressor
      responses, which may inhibit sodium intake. Noradrenaline (NOR) acting on alpha2
      adrenoceptors in the lateral parabrachial nucleus (LPBN) deactivates inhibitory
      mechanisms increasing fluid depletion-induced sodium intake. In the present
      study, we investigated: (1) water and 1.8% NaCl intake in rats treated with
      pilocarpine i.p. or carbachol i.c.v. combined with NOR into the LPBN; (2) if
      inhibitory signals from cardiovascular receptors are blocked by NOR in the LPBN.
      Male Holtzman rats with stainless steel guide-cannulas implanted in the lateral
      ventricle and bilaterally in the LPBN were used. Bilateral injections of NOR
      (80nmol/0.2MUl) into the LPBN decreased water intake (0.8+/-0.3, vs. saline
      (SAL): 2.9+/-0.3ml/180min) induced by pilocarpine (1mg/kg of body weight) i.p.,
      without changing 1.8% NaCl intake (0.8+/-2.4, vs. SAL: 0.5+/-0.3ml/180min).
      Prazosin (1mg/kg of body weight) i.p. blocked pressor responses and increased
      water and 1.8% NaCl intake (6.3+/-1.7 and 14.7+/-3.5ml/180min, respectively) in
      rats treated with pilocarpine combined with NOR into the LPBN. Prazosin i.p. also
      increased 1.8% NaCl intake in rats treated with carbachol i.c.v combined with NOR
      into the LPBN. The results suggest that different signals inhibit sodium intake
      in rats treated with cholinergic agonists, among them those produced by increases
      of arterial pressure that are not efficiently deactivated by NOR acting in the
      LPBN.

PMID- 25977167
TI  - RAD genotyping reveals fine-scale genetic structuring and provides powerful
      population assignment in a widely distributed marine species, the American
      lobster (Homarus americanus).
AB  - Deciphering genetic structure and inferring connectivity in marine species have
      been challenging due to weak genetic differentiation and limited resolution
      offered by traditional genotypic methods. The main goal of this study was to
      assess how a population genomics framework could help delineate the genetic
      structure of the American lobster (Homarus americanus) throughout much of the
      species' range and increase the assignment success of individuals to their
      location of origin. We genotyped 10 156 filtered SNPs using RAD sequencing to
      delineate genetic structure and perform population assignment for 586 American
      lobsters collected in 17 locations distributed across a large portion of the
      species' natural distribution range. Our results revealed the existence of a
      hierarchical genetic structure, first separating lobsters from the northern and
      southern part of the range (FCT  = 0.0011; P-value = 0.0002) and then revealing a
      total of 11 genetically distinguishable populations (mean FST  = 0.00185; CI:
      0.0007-0.0021, P-value < 0.0002), providing strong evidence for weak, albeit fine
      scale population structuring within each region. A resampling procedure showed
      that assignment success was highest with a subset of 3000 SNPs having the highest
      FST . Applying Anderson's (Molecular Ecology Resources, 2010, 10, 701) method to
      avoid 'high-grading bias', 94.2% and 80.8% of individuals were correctly assigned
      to their region and location of origin, respectively. Lastly, we showed that
      assignment success was positively associated with sample size. These results
      demonstrate that using a large number of SNPs improves fine-scale population
      structure delineation and population assignment success in a context of weak
      genetic structure. We discuss the implications of these findings for the
      conservation and management of highly connected marine species, particularly
      regarding the geographic scale of demographic independence. 

PMID- 25977168
TI  - Olfactory bulb volume predicts therapeutic outcome in major depression disorder.
AB  - The volume of the olfactory bulb (OB) is strongly reduced in patients with major
      depressive disorder (MDD) and this group exhibits markedly decreased olfactory
      function. It has been suggested that olfactory input is important for maintaining
      balance in limbic neurocircuits. The aim of our study was to investigate whether
      reduced OB volume is associated with response to therapy in MDD. Twenty-four
      inpatients (all women, age 21-49 years, mean 38 +/- 10 years SD) with MDD and 36
      healthy controls (all women, age 20-52 years, mean 36 +/- 10 years SD) underwent
      structural MRI. OB volume was compared between responders (N = 13) and non
      responders (N = 11) to psychotherapy. Retest of OB volume was performed about 6
      months after the end of therapy in nine of the patients. Therapy responders
      exhibited no significant difference in OB volume compared to healthy controls.
      However, average OB volume of non-responders was 23 % smaller compared to
      responders (p = .0011). Furthermore, OB volume was correlated with the change of
      depression severity (r = .46, p = .024). Volume of the OB did not change in the
      course of therapy. OB volume may be a biological vulnerability factor for the
      occurrence and/or maintenance of depression, at least in women.

PMID- 25977169
TI  - Transcriptomic profiling of Forkhead box transcription factors in adult
      glioblastoma multiforme.
AB  - BACKGROUND: The Forkhead box transcription factor (FOX) family plays an essential
      role in embryogenesis, especially during brain development. Our hypothesis is
      that de-regulation of FOX genes may contribute to aggressive tumor biology and
      therapy resistance in patients with glioblastoma multiforme (GBM). MATERIALS AND
      METHODS: Univariate and multivariate analyses were performed to evaluate
      prognostic significance of transcript levels of 31 FOX genes in a test set of GBM
      patients (n=191) and validated them in The Cancer Genome Atlas (TCGA) cohort
      comprising of 508 adult cases of GBM. The predictive significance of key FOX
      genes was investigated in patients who received chemotherapy or radiotherapy.
      RESULTS: Low FOXA2 mRNA, low FOXN2 mRNA, low FOXN3 mRNA and high FOXG1 mRNA were
      associated with poor survival in the test and TCGA validation cohorts. In
      multivariate analysis, low FOXA2 mRNA, low FOXN2 mRNA, low FOXN3 mRNA and high
      FOXG1 mRNA remained independently associated with poor survival in the test and
      TCGA validation cohorts. In patients who received chemotherapy or radiotherapy,
      low FOXA2 mRNA, low FOXN2 mRNA and high FOXG1 mRNA correlated with adverse
      outcomes in the TCGA validation cohort. CONCLUSION: To our knowledge, our data
      provide the first comprehensive clinical evidence that FOXA2, FOXN2, FOXN3 and
      FOXG1 are promising biomarkers of GBM and warrant further investigation.

PMID- 25977170
TI  - Expression of metastasis-associated gene-1 is associated with bone invasion and
      tumor stage in human pituitary adenomas.
AB  - BACKGROUND: Metastasis associated gene-1 (MTA1), was initially discovered in
      aggressive human cancer cell lines and has been subsequently associated with the
      invasiveness and metastatic potential of cancer cells. MATERIALS AND METHODS: In
      the present study, we evaluated the expression levels of MTA1 in a cohort of
      human pituitary tumors (n=95) and examined the relationship between MTA1
      expression and the pathological, clinical and aggressiveness of these tumors.
      RESULTS: MTA1 was expressed at significantly higher levels in large tumors and in
      those with higher tumor grade. It was also observed that tumors that had invaded
      the suprasellar bones and tumors that destructed the sella had significantly
      higher levels than those without bone involvement (p<005). Although there did not
      appear to exist any relationship between MTA1 and cystic lesions in the tumors,
      endocrine-active tumors, namely those secreting prolactin, growth hormone,
      Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) had significantly
      lower MTA1 transcript levels than inactive tumors. CONCLUSION: MTA1 is associated
      with the aggressive nature of pituitary tumors and may be a potential therapeutic
      target in this tumor type.

PMID- 25977171
TI  - Druggable cancer secretome: neoplasm-associated traits.
AB  - BACKGROUND: The genome association databases provide valuable clues to identify
      novel targets for cancer diagnosis and therapy. Genes harboring phenotype
      associated polymorphisms for neoplasm traits can be identified using diverse
      bioinformatics tools. The recent availability of various protein expression
      datasets from normal human tissues, including the body fluids, enables for
      baseline expression profiling of the cancer secretome. Chemoinformatics
      approaches can help identify drug-like compounds from the protein 3D structures.
      MATERIALS AND METHODS: The National Center for Biotechnology Information (NCBI)
      Phenome Genome Integrator (PheGenI) tool was enriched for neoplasm-associated
      traits. The neoplasm genes were characterized using diverse bioinformatics tools
      for pathways, gene ontology, genome-wide association, protein expression and
      functional class. Chemogenomics analysis was performed using the canSAR protein
      annotation tool. RESULTS: The neoplasm-associated traits segregated into 1,305
      genes harboring 2,837 single nucleotide polymorphisms (SNPs). Also identified
      were 65 open reading frames (ORFs) encompassing 137 SNPs. The neoplasm genes and
      the associated SNPs were classified into distinct tumor types. Protein expression
      in the secretome was seen for 913 of the neoplasm-associated genes, including 17
      novel uncharacterized ORFs. Druggable proteins, including enzymes, transporters,
      channel proteins and receptors, were detected. Thirty-four novel druggable lead
      genes emerged from these studies, including seven cancer lead targets.
      Chemogenomics analysis using the canSAR protein annotation tool identified 168
      active compounds (<1 MUM) for the neoplasm genes in the body fluids. Among these,
      7 most active lead compounds with drug-like properties (1-600 nM) were identified
      for the cancer lead targets, encompassing enzymes and receptors. CONCLUSION: Over
      seventy percent of the neoplasm trait-associated genes were detected in the body
      fluids, such as ascites, blood, tear, milk, semen, urine, etc. Ligand-based
      druggabililty analysis helped establish lead prioritization. The association of
      these proteins with diverse cancer types and other diseases provides a framework
      to develop novel diagnosis and therapy targets.

PMID- 25977172
TI  - Effect of STAT3 inhibition on the metabolic switch in a highly STAT3-activated
      lymphoma cell line.
AB  - BACKGROUND: Signal transducer and activator of transcription (STAT)3 is involved
      in a metabolic shift in cancer cells, the Warburg effect through its pro
      oncogenic activity. To develop efficient STAT3 inhibitors against cancer cells,
      novel proteomic and metabolic target molecules need to be explored using multi
      omics approaches in the context of STAT3 gene inhibition-mediated tumor growth
      suppression. MATERIALS AND METHODS: We found that short hairpin (sh)RNA-mediated
      STAT3 inhibition suppressed tumor growth in a highly STAT3-activated lymphoma
      cell line, SCC-3 cells, and we investigated the effect of STAT3 inhibition on
      metabolic switching using 2-dimensional differential gel electrophoresis and
      capillary electrophoresis-time of flight-mass spectrometry. RESULTS: We
      identified latexin as a proteomic marker candidate and metabolic enzymes
      including fructose-bisphosphate aldolase A (ALDOA) as a metabolic marker
      candidate for STAT3-targeting therapy using STAT3-specific shRNA gene
      transduction. In particular, latexin expression was up-regulated in four STAT3
      activated cancer cell lines including SCC-3 transduced with STAT3-specific shRNA.
      The up-regulation of latexin was identified in SCC-3 tumors transplanted to nude
      mice after treatment with STAT3 inhibitor. CONCLUSION: Our results suggest that
      STAT3 inactivation reverses the glycolytic shift by down-regulating key enzymes
      and that it induces up-regulation of latexin as a tumor-suppressor molecule,
      which partially results in cancer cell apoptosis and tumor growth suppression.

PMID- 25977173
TI  - Caveolin-1, breast cancer and ionizing radiation.
AB  - Breast cancer (BC) recovery has increased in recent years thanks to efforts of
      Omics-based research in this field. However, despite the important results
      obtained, BC remains a complex multifactorial pathology that is difficult to
      treat appropriately. Caveolin-1 (CAV1), the basic constituent protein of
      specialized plasma membrane invaginations called caveolae, is emerging as a
      potential therapeutic biomarker in BC. This factor may modulate BC response to
      chemotherapy and radiation therapy. In addition, recent reports describe the key
      role of CAV1 during cell response to oxidative stress. The aim of the present
      review was to describe the biological roles of CAV1 in BC considering its
      contrasting dual functions as an oncogene and as a tumor suppressor. In addition,
      we report on how CAV1 may contribute to tumor cell response to ionizing radiation
      treatment. Finally, new roles of CAV1 in BC both on epithelium and stroma may be
      useful as prognostic indicators for patient treatment and help clinicians in the
      selection of the best personalized therapy. 

PMID- 25977174
TI  - Topological network analysis of differentially expressed genes in cancer cells
      with acquired gefitinib resistance.
AB  - BACKGROUND/AIM: Despite great effort to elucidate the process of acquired
      gefitinib resistance (AGR) in order to develop successful chemotherapy, the
      precise mechanisms and genetic factors of such resistance have yet to be
      elucidated. MATERIALS AND METHODS: We performed a cross-platform meta-analysis of
      three publically available microarray datasets related to cancer with AGR. For
      the top 100 differentially expressed genes (DEGs), we clustered functional
      modules of hub genes in a gene co-expression network and a protein-protein
      interaction network. We conducted a weighted correlation network analysis of
      total DEGs in microarray dataset GSE 34228. The identified DEGs were functionally
      enriched by Gene Ontology (GO) function and KEGG pathway. RESULTS: We identified
      a total of 1,033 DEGs (510 up-regulated, 523 down-regulated, and 109 novel
      genes). Among the top 100 up- or down-regulated DEGs, many genes were found in
      different types of cancers and tumors. Through integrative analysis of two
      systemic networks, we selected six hub DEGs (Pre-B-cell leukemia homeobox1,
      Transient receptor potential cation channel subfamily C member 1, AXL receptor
      tyrosine kinase, S100 calcium binding protein A9, S100 calcium binding protein
      A8, and Nucleotide-binding oligomerization domain containing 2) associated with
      calcium homeostasis and signaling, apoptosis, transcriptional regulation, or
      chemoresistance. We confirmed a correlation of expression of these genes in the
      microarray dataset. CONCLUSION: Our study may lead to comprehensive insights into
      the complex mechanism of AGR and to novel gene expression signatures useful for
      further clinical studies.

PMID- 25977175
TI  - Adolescents' and parents' views of Child and Adolescent Mental Health Services
      (CAMHS) in Ireland.
AB  - Service user involvement is essential for quality care in the Child and
      Adolescent Mental Health Services (CAMHS). This study was conducted to explore
      adolescents' and parents' experiences of CAMHS in relation to accessibility,
      approachability and appropriateness. This study used a descriptive qualitative
      design, and focus groups and single interviews were conducted with adolescents (n
      = 15) and parents (n = 32) from three mental health clinics. Data were analysed
      using thematic analysis. Accessing mental health services was a challenging
      experience for many parents and adolescents due to knowledge deficit, lack of
      information and limited availability of specialist services. Some parents and
      adolescents reported positive experiences while others reported negative
      experiences. They expressed a need for more information, involvement in decision
      making, flexible scheduling of appointments, school support and parent support
      groups. The nature and quality of the relationship with staff was critical to
      positive experience with the service; therefore, frequent changes of medical
      staff was disruptive. Mental health nurses can play a vital role in ensuring
      continuity, assessing adolescents' participation preferences and advocating for
      their information needs with other members of the interdisciplinary team.

PMID- 25977176
TI  - Evaluation of effect of self-examination and physical examination on breast
      cancer.
AB  - BACKGROUND: Breast cancer is the number one cancer of women in the world. More
      than 90% of breast cancers can be cured with early diagnosis followed by
      effective multimodality treatment. The efficacy of screening by breast self
      examination (BSE) and breast physical examination (BPx) is best evaluated using
      randomized screening trials. METHOD: A total of 12,660 women aged 35-64 years,
      6330 in the intervention group and 6330 in the control group, were randomly
      selected from four areas of Yazd city, I.R. of Iran. The number of detected
      cancers along with kind of cancer, staging of cancer, the route of detected
      cancer and the number of deaths during the first 5 years of the study were
      collected and analyzed. RESULTS: No significance difference between the two
      groups was seen in respect to socio-demographic and socio-economic variables (P >
      0.05). Subjects in the intervention group had a response rate of 83.5% for
      attending the health center and 80.2% for visiting the assigned surgeon. A total
      of 31 and 13 new cases of breast cancer were identified in the intervention and
      control groups, respectively, of which 48.5% of cases in the intervention group
      were <50 yr of age. A significant difference between the cumulative incidence of
      breast cancer in the two groups with a ratio of 2.4 was observed. CONCLUSION: BSE
      & BPx have a significant effect in detecting breast cancers at early stages (<3)
      suggesting they are effective screening tests with high availability and low
      costs that can be applied at the community level.

PMID- 25977178
TI  - End-of-life decision-making in respiratory intermediate units: A european survey.

PMID- 25977177
TI  - Patterns and severity of vincristine-induced peripheral neuropathy in children
      with acute lymphoblastic leukemia.
AB  - Vincristine, a critical component of combination chemotherapy treatment for
      pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced
      peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12
      months from newly diagnosed children with ALL (N = 128) aged 1-18 years who
      received vincristine at one of four academic children's hospitals. VIPN
      assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine
      (TNS(c)-PV), National Cancer Institute Common Terminology Criteria for Adverse
      Events (CTCAE(c)), Balis(c) grading scale, and Pediatric Neuropathic Pain
      Scale(c)-Five (PNPS(c)-5). Of children who provided a full TNS(c)-PV score,
      85/109 (78%) developed VIPN (TNS(c)-PV >=4). Mean TNS(c)-PV, grading scale, and
      pain scores were low. CTCAE(c)-derived grades 3 and 4 sensory and motor VIPN
      occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve
      in months 8-12 despite decreasing dose density. VIPN was worse in older children.
      Partition cluster analysis revealed 2-3 patient clusters; one cluster (n = 14)
      experienced severe VIPN. In this population, VIPN occurs more commonly than
      previous research suggests, persists throughout the first year of treatment, and
      can be severe. 

PMID- 25977180
TI  - Long-term follow-up of thoracoscopic talc pleurodesis for primary spontaneous
      pneumothorax.

PMID- 25977179
TI  - Computed tomography screening and lung cancer outcomes.

PMID- 25977181
TI  - Radiologic and clinical features of copd patients with discordant pulmonary
      physiology - Lessons from alpha-1 antitrypsin deficiency.

PMID- 25977182
TI  - Daytime sleepiness and polysomnographic variables in sleep apnoea patients.

PMID- 25977183
TI  - Z-ligustilide ameliorated ultraviolet B-induced oxidative stress and inflammatory
      cytokine production in human keratinocytes through upregulation of Nrf2/HO-1 and
      suppression of NF-kappaB pathway.
AB  - Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety
      of skin disorders including skin inflammation through reactive oxygen species
      (ROS) and inflammatory mediator production. Here, we investigated the effect of Z
      ligustilide (Z-lig), an active ingredient isolated from the medicinal plants
      Cnidium officinale and Angelica acutiloba, on UVB-induced ROS generation and
      inflammatory mediator production in normal human epidermal keratinocytes (NHEKs)
      as well as its underlying mechanisms. Z-lig significantly rescued UVB-induced
      NHEKs damage in a dosage-dependent manner. Pretreatment of NHEKs with Z-lig
      inhibited UVB-induced ROS production in NHEKs. Both silencing the nuclear factor
      E2-related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a
      haeme oxygenase-1 (HO-1) inhibitor, cancelled the inhibitory effect of Z-lig on
      UVB-induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z-lig
      reduced UVB-induced nuclear factor kappa B (NF-kappaB)-dependent inflammatory
      mediators (IL-6, IL-8 and MCP-1) production at both mRNA and protein level. In
      the presence of Z-lig, UVB-induced NF-kappaB subunit p65 nuclear translocation
      was abolished, and the IkappaBalpha degradation was suppressed. Taken together,
      these findings suggest that Z-lig can suppress UVB-induced ROS generation through
      Nrf2/HO-1 upregulation and inflammation by suppressing the NF-kappaB pathway,
      suggesting that Z-lig may be beneficial in protecting skin from UVB exposure. 

PMID- 25977184
TI  - Development of a time-resolved fluoroimmunoassay for Epstein-Barr virus viral
      capsid antigen IgA antibody in human serum.
AB  - Viral capsid antigen (VCA) IgA is one of the most commonly tested antibodies for
      Epstein-Barr virus (EBV) in the clinic and is a proven biomarker to predict the
      risk of nasopharyngeal carcinoma (NPC) and other diseases. At present, a VCA-IgA
      antibody is used for clinical diagnosis by enzyme-linked immunosorbent assay
      (ELISA), which can detect samples only qualitatively or semi-quantitatively, with
      unsatisfactory sensitivity and specificity. In this study, an indirect time
      resolved fluoroimmunoassay (TRFIA) using Eu(3+) labeled mouse anti-human IgA
      monoclonal antibodies as a tracer was developed. This method produced a linear
      range of 0-30 AU/mL, with a limit of detection of 0.018 AU/mL. The intra- and
      inter-assay precisions were 1.62-4.30% and 3.56-7.57%, respectively. TRFIA showed
      no cross-reactivity against potentially interfering substances and a better
      sensitivity and specificity compared with commercial ELISA. This study confirmed
      that an indirect TRFIA meets the requirement for clinical testing and could be an
      alternative to detect VCA-IgA levels in human serum in the clinic.

PMID- 25977185
TI  - Development of a multiplex lateral flow strip test for foot-and-mouth disease
      virus detection using monoclonal antibodies.
AB  - Foot-and-mouth disease (FMD) is one of the world's most highly contagious animal
      diseases with tremendous economic consequences. A rapid and specific test for FMD
      diagnosis at the site of a suspected outbreak is crucial for the implementation
      of control measures. This project developed a multiplex lateral flow
      immunochromatographic strip test (multiplex-LFI) for the rapid detection and
      serotyping of FMD viruses. The monoclonal antibodies (mAbs) against serotypes O,
      A, and Asia 1 were used as capture mAbs. The mAbs were conjugated with
      fluorescein, rhodamine or biotin for serotype O, A and Asia 1, respectively. The
      detection mAbs which consisted of a serotype-independent mAb in combination with
      one serotype A-specific mAb and one Asia 1-specific mAb, were each colloidal gold
      conjugated. The strips used in this study contained one control line and three
      test lines, which corresponded to one of the three serotypes, O, A or Asia 1. The
      newly developed multiplex-LFI strip test specifically identified serotype O
      (n=46), A (n=45) and Asia 1 (n=17) in all tested field isolates. The sensitivity
      of this strip test was comparable to the double antibody sandwich ELISA for
      serotypes O and A, but lower than the ELISA for serotype Asia 1. The multiplex
      LFI strip test identified all tissue suspensions from animals that were
      experimentally inoculated with serotypes O, A or Asia 1. FMD viruses were
      detected in 38% and 50% of the swab samples from the lesion areas of
      experimentally inoculated sheep for serotypes O and A, respectively. The
      capability of the multiplex-LFI strip tests to produce rapid results with high
      specificity for FMD viruses of multiple serotypes makes this test a valuable tool
      to detect FMD viruses at outbreak sites. 

PMID- 25977186
TI  - Development and evaluation of an immunochromatographic strip for rapid detection
      of capsid protein antigen p27 of avian leukosis virus.
AB  - A rapid immunochromatographic strip for detecting capsid protein antigen p27 of
      avian leukosis virus was successfully developed based on two high-affinity
      monoclonal antibodies. The test strip could detect not only 600pg purified
      recombinant p27 protein but also quantified avian leukosis virus as low as 70
      TCID50, which has comparative sensitivity to the commercial enzyme-linked
      immunosorbent assay (ELISA) kit. For the evaluation of this test strip, 1100
      samples consisting of cloacal swabs, meconium collected from the earliest stool
      of one day old chicken and virus isolates were assessed both by the strip and by
      the commercial ELISA kit. The agreement between these two tests was 93.91%,
      93.42% and 100%, respectively. The sensitivity and specificity of the strip were
      also calculated by using the ELISA kit as the standard. This
      immunochromatographic strip provides advantages of rapid and simple detection of
      capsid protein antigen p27 of avian leukosis virus, which could be applied as an
      on-site testing assay and used for control and eradication programs of avian
      leukosis disease. 

PMID- 25977187
TI  - Therapeutic applications of human adipose-derived stromal cells for soft tissue
      reconstruction.
AB  - Adipose derived stromal cells (ASCs) are a multipotent cell population derived
      from the stromal vascular fraction of lipoaspirate. Given their relatively broad
      differentiation potential and paracrine capabilities, ASCs represent a readily
      accessible, endogenous resource for novel reconstructive strategies. In
      particular, augmentation of autologous fat grafts with ASCs has already been
      employed clinically for restoration of soft tissue defects. While fat grafting
      alone remains highly unpredictable, enrichment of fat with supplemental ASCs,
      also known as cell-assisted lipotransfer (CAL), has been shown to significantly
      enhance volume retention. How addition of these cells to fat grafts results in
      improved outcomes, however, remains poorly understood. Furthermore, the safety of
      CAL in the setting of prior malignancy and post-radiation wound beds has yet to
      be fully determined, an important consideration for its use in cancer
      reconstruction. Thus, further studies to determine the how and why behind the
      efficacy of CAL are necessary before it can be widely adopted as a safe and
      reliable surgical technique. 

PMID- 25977188
TI  - The CRISPR/Cas9 genome editing methodology as a weapon against human viruses.
AB  - Viruses are a therapeutic challenge since their life cycles occur within the host
      cells and often utilize cellular proteins and hence it is harder to identify
      therapeutic targets compared to bacteria, which have their own cellular
      metabolism that is quite different from the host and often present unique targets
      such as enzymes, etc. Nevertheless, viral proteins may present useful targets for
      therapy, e.g., small molecule inhibitors of viral polymerases, or prevention,
      e.g., viral coat proteins for vaccination. However, some viruses may enter an
      inactive state of persistence or latency where no or very few viral proteins are
      produced. Thus, methodologies that are specifically able to target nucleotide
      sequences within viral genomes would be a useful addition to the antiviral
      armamentarium. Such a methodology is the clustered regulatory interspaced short
      palindromic repeat (CRISPR)-associated 9 (Cas9) system, which is effective,
      specific, and versatile and provides unprecedented control over genome editing.
      Here, we will discuss how CRISPR/Cas9 has been used against human viruses and
      future prospects for novel therapeutic approaches. 

PMID- 25977189
TI  - Liquid biopsy in liver cancer.
AB  - Liver cancer has become the second cause of cancer-related death worldwide. Most
      patients are still diagnosed at intermediate or advanced stage, where potentially
      curative treatment options are not recommended. Unlike other solid tumors, there
      are no validated oncogenic addiction loops and the only systemic agent to improve
      survival in advanced disease is sorafenib. All phase 3 clinical trials testing
      molecular therapies after sorafenib have been negative, none of which selected
      patients based on predictive biomarkers of response. Theoretically, analysis of
      circulating cancer byproducts (e.g., circulating tumor cells, cell-free nucleic
      acids), namely "liquid biopsy," could provide easy access to molecular tumor
      information, improve patients' stratification and allow to assess tumor dynamics
      over time. Recent technical developments and preliminary data from other
      malignancies indicate that liquid biopsy might have a role in the future
      management of cancer patients. 

PMID- 25977191
TI  - Advances in gene therapy for heart failure.
AB  - Chronic heart failure is expected to increase its social and economic burden as a
      consequence of improved survival in patients with acute cardiac events. Cardiac
      gene therapy holds significant promise in heart failure treatment for patients
      with currently very limited or no treatment options. The introduction of adeno
      associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy,
      and now it is the primary vector of choice for chronic heart failure gene therapy
      in clinical and preclinical studies. Recently, there has been significant
      progress towards clinical translation in this field spearheaded by AAV-1 mediated
      sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic
      advanced heart failure patients. Meanwhile, several independent laboratories are
      reporting successful gene therapy approaches in clinically relevant large animal
      models of heart failure and some of these approaches are expected to enter
      clinical trials in the near future. This review will focus on gene therapy
      approaches targeting heart failure that is in clinical trials and those close to
      its initial clinical trial application. 

PMID- 25977190
TI  - New approaches for the immunotherapy of acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a set of related diseases characterized by the
      immortalization and uncontrolled expansion of myeloid precursor cells. Core
      therapy for AML has remained unchanged for nearly 30 years, and survival rates
      remain unsatisfactory. However, advances in the immunotherapy of AML have created
      opportunities for improved outcomes. Enforcing a tumor-specific immune response
      through the re-direction of the adaptive immune system, which links remarkable
      specificity with potent cytotoxic effector functions, has proven particularly
      compelling. This may be coupled with immune checkpoint blockade and conventional
      therapies for optimal effect. Engineered antibodies are currently in use in AML
      and the repertoire of available therapeutics will expand. NK cells have shown
      effectiveness in this disease. New methods to optimize their activation and the
      targeting of AML show potential. Most significantly, adoptive immunotherapy with
      tumor-specific T cells, and particularly T cells re-directed using genetically
      introduced TCR or chimeric antigen receptors, have demonstrated promise. Each of
      these approaches has unique benefits and challenges that we explore in this
      review. 

PMID- 25977192
TI  - Advances in strategies and methodologies in cancer immunotherapy.
AB  - Since the invention of Coley's toxin by William Coley in early 1900s, the path
      for cancer immunotherapy has been a convoluted one. Although still not considered
      standard of care, with the FDA approval of trastuzumab, Provenge and ipilimumab,
      the medical and scientific community has started to embrace the possibility that
      immunotherapy could be a new hope for cancer patients with otherwise untreatable
      metastatic diseases. This review aims to summarize the development of some major
      strategies in cancer immunotherapy, from the earliest peptide vaccine and
      transfer of tumor specific antibodies/T cells to the more recent dendritic cell
      (DC) vaccines, whole cell tumor vaccines, and checkpoint blockade therapy.
      Discussion of some major milestones and obstacles in the shaping of the field and
      the future perspectives is included. Photoimmunotherapy is also reviewed as an
      example of emerging new therapies combining phototherapy and immunotherapy. 

PMID- 25977193
TI  - Wnt signaling in dendritic cells: its role in regulation of immunity and
      tolerance.
AB  - A fundamental puzzle in immunology is how the immune system launches robust
      immunity against pathogens while maintaining a state of tolerance to the body's
      own tissues and the trillions of commensal microorganisms and food antigens that
      confront them every day. Innate immune cells, such as dendritic cells (DCs) and
      macrophages, play a fundamental role in this process. Emerging studies have
      highlighted that the Wnt signaling pathway, particularly in DCs, plays a major
      role in regulating tolerance versus immunity. Here, we review our current
      understanding of how Wnt-signaling shapes the immune response and, in addition,
      highlight unanswered questions, the solution of which will be imperative in the
      rational exploitation of this pathway in vaccine design and immune therapy. 

PMID- 25977194
TI  - BMP4 promotes human Sertoli cell proliferation via Smad1/5 and ID2/3 pathway and
      its abnormality is associated with azoospermia.
AB  - Sertoli cell plays critical roles in regulating testis development and
      spermatogenesis. Any change in the number or biological functions of Sertoli
      cells can affect the normal formation of spermatozoa. However, the roles and
      molecular mechanisms of factors in controlling the fate determinations of human
      Sertoli cells and underlying male infertility remain unknown. Here we have for
      the first time explored the function and signaling pathway of BMP4 in regulating
      adult human Sertoli cells and their association with non-obstructive azoospermia
      (NOA) patients. Immunocytochemistry and immunohistochemistry revealed that BMP4
      and its multiple receptors were present in human Sertoli cells. Cell
      proliferation and BrdU incorporation assays showed that BMP4 promoted DNA
      synthesis and proliferation of Sertoli cells. In contrast, BMP4 antagonist noggin
      and BMP4 knockdown reduced the division of Sertoli cells. Moreover, BMP4
      knockdown inhibited the synthesis of FGF2, SCF, zonula occludens 1, and claudin
      11 but enhanced p27kip1 transcription. BMP4 activated Smad1/5 phosphorylation and
      upregulated ID2 and ID3 transcription, whereas noggin counteracted these
      increases. Significantly, tissue arrays disclosed that overexpression of BMP4 may
      be associated with Sertoli cell-only syndrome and maturation arrest in
      spermatogonia or spermatocytes. BMP4 was identified as the first autocrine factor
      that regulates the proliferation and protein synthesis of human Sertoli cells via
      Smad1/5 and ID2/3 and its abnormality is associated with human non-obstructive
      azoospermia patients. This study thus provides novel insights into molecular
      mechanism underlying adult human Sertoli cell growth and offers new targets for
      gene therapy of male infertility. 

PMID- 25977195
TI  - Non-t(6;9) and Non-Inv(3) Balanced Chromosomal Rearrangements Are Associated With
      Poor Survival Outcomes in Myelodysplastic Syndromes.
AB  - BACKGROUND: Cytogenetics is an important predictor of survival in patients with
      myeloid malignancies including myelodysplastic syndromes (MDS). The roles of
      balanced chromosomal rearrangements (BCR) specifically balanced translocations
      and inversions in MDS are less established. We hypothesized that BCR are commonly
      found in MDS and might confer important prognostic and therapeutic effect.
      PATIENTS AND METHODS: Cytogenetic, hematologic, clinical, and survival data from
      a total of 302 MDS patients seen at the Cleveland Clinic between the years 2002
      and 2011 were collected. Direct sequencing for genes relevant in MDS
      pathophysiology was performed on patients with BCR. Categorical data were
      analyzed using the chi2 test and survival outcomes were analyzed using the Kaplan
      Meier method. RESULTS: Twenty-three patients (8%) carried non-t(6;9) and non
      inv(3) BCR. These patients had short overall survival (OS) similar to patients
      with poor risk cytogenetics, defined according to the International Prognostic
      Scoring System, which was not altered by new single-nucleotide polymorphism
      arrays or acquired somatic uniparental disomy lesions. Among the detected somatic
      mutations, only patients harboring mutations in the RNA splicing gene
      serine/arginine-rich splicing factor 2 (SRSF2) conferred worse outcomes in this
      group of patients. Therapeutically, patients who received allogeneic
      hematopoietic cell transplantations had better OS compared with patients treated
      with pharmacologic therapies or best supportive care only. CONCLUSION: BCR are
      not common in MDS and are associated with poor survival, which might be
      influenced by the presence of SRSF2 mutation.

PMID- 25977196
TI  - [Coronary pseudoaneurysm after percutaneous treatment of a coronary perforation].
AB  - Coronary pseudoaneurysms are rare and usually occur after percutaneous
      procedures, spontaneous dissections, aortocoronary bypass, or chest trauma.
      Although most of the cases are casual, other patients present as acute myocardial
      infarction, fistula formation or cardiac tamponade. We report the case of a
      coronary pseudoaneurysm after percutaneous treatment of a coronary perforation. 

PMID- 25977197
TI  - Automated personalized feedback for physical activity and dietary behavior change
      with mobile phones: a randomized controlled trial on adults.
AB  - BACKGROUND: A dramatic rise in health-tracking apps for mobile phones has
      occurred recently. Rich user interfaces make manual logging of users' behaviors
      easier and more pleasant, and sensors make tracking effortless. To date, however,
      feedback technologies have been limited to providing overall statistics,
      attractive visualization of tracked data, or simple tailoring based on age,
      gender, and overall calorie or activity information. There are a lack of systems
      that can perform automated translation of behavioral data into specific
      actionable suggestions that promote healthier lifestyle without any human
      involvement. OBJECTIVE: MyBehavior, a mobile phone app, was designed to process
      tracked physical activity and eating behavior data in order to provide
      personalized, actionable, low-effort suggestions that are contextualized to the
      user's environment and previous behavior. This study investigated the technical
      feasibility of implementing an automated feedback system, the impact of the
      suggestions on user physical activity and eating behavior, and user perceptions
      of the automatically generated suggestions. METHODS: MyBehavior was designed to
      (1) use a combination of automatic and manual logging to track physical activity
      (eg, walking, running, gym), user location, and food, (2) automatically analyze
      activity and food logs to identify frequent and nonfrequent behaviors, and (3)
      use a standard machine-learning, decision-making algorithm, called multi-armed
      bandit (MAB), to generate personalized suggestions that ask users to either
      continue, avoid, or make small changes to existing behaviors to help users reach
      behavioral goals. We enrolled 17 participants, all motivated to self-monitor and
      improve their fitness, in a pilot study of MyBehavior. In a randomized two-group
      trial, investigators randomly assigned participants to receive either
      MyBehavior's personalized suggestions (n=9) or nonpersonalized suggestions (n=8),
      created by professionals, from a mobile phone app over 3 weeks. Daily activity
      level and dietary intake was monitored from logged data. At the end of the study,
      an in-person survey was conducted that asked users to subjectively rate their
      intention to follow MyBehavior suggestions. RESULTS: In qualitative daily diary,
      interview, and survey data, users reported MyBehavior suggestions to be highly
      actionable and stated that they intended to follow the suggestions. MyBehavior
      users walked significantly more than the control group over the 3 weeks of the
      study (P=.05). Although some MyBehavior users chose lower-calorie foods, the
      between-group difference was not significant (P=.15). In a poststudy survey,
      users rated MyBehavior's personalized suggestions more positively than the
      nonpersonalized, generic suggestions created by professionals (P<.001).
      CONCLUSIONS: MyBehavior is a simple-to-use mobile phone app with preliminary
      evidence of efficacy. To the best of our knowledge, MyBehavior represents the
      first attempt to create personalized, contextualized, actionable suggestions
      automatically from self-tracked information (ie, manual food logging and
      automatic tracking of activity). Lessons learned about the difficulty of manual
      logging and usability concerns, as well as future directions, are discussed.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT02359981;
      https://clinicaltrials.gov/ct2/show/NCT02359981 (Archived by WebCite at
      http://www.webcitation.org/6YCeoN8nv).

PMID- 25977199
TI  - A Collaborative Learning Network Approach to Improvement: The CUSP Learning
      Network.
AB  - BACKGROUND: Collaborative improvement networks draw on the science of
      collaborative organizational learning and communities of practice to facilitate
      peer-to-peer learning, coaching, and local adaption. Although significant
      improvements in patient safety and quality have been achieved through
      collaborative methods, insight regarding how collaborative networks are used by
      members is needed. Improvement Strategy: The Comprehensive Unit-based Safety
      Program (CUSP) Learning Network is a multi-institutional collaborative network
      that is designed to facilitate peer-to-peer learning and coaching specifically
      related to CUSP. Member organizations implement all or part of the CUSP
      methodology to improve organizational safety culture, patient safety, and care
      quality. Qualitative case studies developed by participating members examine the
      impact of network participation across three levels of analysis (unit, hospital,
      health system). In addition, results of a satisfaction survey designed to
      evaluate member experiences were collected to inform network development.
      RESULTS: Common themes across case studies suggest that members found value in
      collaborative learning and sharing strategies across organizational boundaries
      related to a specific improvement strategy. CONCLUSION: The CUSP Learning Network
      is an example of network-based collaborative learning in action. Although this
      learning network focuses on a particular improvement methodology-CUSP-there is
      clear potential for member-driven learning networks to grow around other methods
      or topic areas. Such collaborative learning networks may offer a way to develop
      an infrastructure for longer-term support of improvement efforts and to more
      quickly diffuse creative sustainment strategies.

PMID- 25977200
TI  - Incident learning in pursuit of high reliability: implementing a comprehensive,
      low-threshold reporting program in a large, multisite radiation oncology
      department.
AB  - BACKGROUND: Incident learning programs have been recognized as cornerstones of
      safety and quality assurance in so-called high reliability organizations in
      industries such as aviation and nuclear power. High reliability organizations are
      distinguished by their drive to continuously identify and proactively address a
      broad spectrum of latent safety issues. Many radiation oncology institutions have
      reported on their experience in tracking and analyzing adverse events and near
      misses but few have incorporated the principles of high reliability into their
      programs. Most programs have focused on the reporting and retrospective analysis
      of a relatively small number of significant adverse events and near misses. To
      advance a large, multisite radiation oncology department toward high reliability,
      a comprehensive, cost-effective, electronic condition reporting program was
      launched to enable the identification of a broad spectrum of latent system
      failures, which would then be addressed through a continuous quality improvement
      process. METHODS: A comprehensive program, including policies, work flows, and
      information system, was designed and implemented, with use of a low reporting
      threshold to focus on precursors to adverse events. RESULTS: In a 46-month period
      from March 2011 through December 2014, a total of 8,504 conditions (average, 185
      per month, 1 per patient treated, 3.9 per 100 fractions [individual treatments])
      were reported. Some 77.9% of clinical staff members reported at least 1
      condition. Ninety-eight percent of conditions were classified in the lowest two
      of four severity levels, providing the opportunity to address conditions before
      they contribute to adverse events. CONCLUSIONS: Results after approximately four
      years show excellent employee engagement, a sustained rate of reporting, and a
      focus on low-level issues leading to proactive quality improvement interventions.

PMID- 25977201
TI  - A qualitative analysis of hospital leaders' opinions about publicly reported
      measures of health care quality.
AB  - BACKGROUND: Hospital leaders play an important role in the success of quality
      improvement (QI) initiatives, yet little is known about how leaders engaged in QI
      currently view quality performance measures. In a follow-up to a quantitative
      study conducted in 2012, a study employing qualitative content analysis was
      conducted to (1) describe leaders' opinions about the quality measures reported
      on the Centers for Medicare & Medicaid Services (CMS) Hospital Compare website,
      (2) to generate hypotheses about barriers/facilitators to improving hospitals'
      performance, and (3) to elicit recommendations about how to improve publicly
      reported quality measures. METHODS: The opinions of leaders from a stratified
      sample of 630 hospitals across the United States regarding quality measures were
      assessed with an open-ended prompt that was part of a 21-item questionnaire about
      quality measures publicly reported by CMS. Their responses were qualitatively
      analyzed in an iterative process, resulting in the identification of the presence
      and frequency of major themes and subthemes. RESULTS: Participants from 131 (21%)
      of the 630 hospitals surveyed replied to the open-ended prompt; 15% were from
      hospitals with higher-than-average performance scores, and 52% were from
      hospitals with lower-than-average scores. Major themes included (1) concerns
      regarding quality measurement (measure validity, importance, and fairness) and/or
      public reporting; 76%); (2) positive views of quality measurement (stimulate
      improvement, focus efforts; 13%); and (3) recommendations for improving quality
      measurement. CONCLUSIONS: Among hospital leaders responding to an open-ended
      survey prompt, some supported the concept of measuring quality, but the majority
      criticized the validity and utility of current quality measures. Although quality
      measures are frequently being reevaluated and new measures developed, the ability
      of such measures to stimulate improvement may be limited without greater buy-in
      from hospital leaders.

PMID- 25977202
TI  - Bringing central line-associated bloodstream infection prevention home: catheter
      maintenance practices and beliefs of pediatric oncology patients and families.
AB  - BACKGROUND: A study was conducted to investigate (1) the extent to which best
      practice central line maintenance practices were employed in the homes of
      pediatric oncology patients and by whom, (2) caregiver beliefs about central line
      care and central line-associated blood stream infection (CLABSI) risk, (3)
      barriers to optimal central line care by families, and (4) educational
      experiences and preferences regarding central line care. METHODS: Researchers
      administered a survey to patients and families in a tertiary care pediatric
      oncology clinic that engaged in rigorous ambulatory and inpatient CLABSI
      prevention efforts. RESULTS: Of 110 invited patients and caregivers, 105
      participated (95% response rate) in the survey (March-May 2012). Of the 50
      respondents reporting that they or another caregiver change central line
      dressings, 48% changed a dressing whenever it was soiled as per protocol (many
      who did not change dressings per protocol also never personally changed
      dressings); 67% reported the oncology clinic primarily cares for their child's
      central line, while 29% reported that an adult caregiver or the patient primarily
      cares for the central line. Eight patients performed their own line care "always"
      or "most of the time." Some 13% of respondents believed that it was "slightly
      likely" or "not at all likely" that their child will get an infection if
      caregivers do not perform line care practices perfectly every time. Dressing
      change practices were the most difficult to comply with at home. Some 18% of
      respondents wished they learned more about line care, and 12% received
      contradictory training. Respondents cited a variety of preferences regarding line
      care teaching, although the majority looked to clinic nurses for modeling line
      care. CONCLUSIONS: Interventions aimed at reducing ambulatory CLABSIs should
      target appropriate educational experiences for adult caregivers and patients and
      identify ways to improve compliance with best-practice care.

PMID- 25977203
TI  - Deployment of rapid response teams by 31 hospitals in a statewide collaborative.

PMID- 25977204
TI  - Methamphetamine injecting is associated with phylogenetic clustering of hepatitis
      C virus infection among street-involved youth in Vancouver, Canada.
AB  - BACKGROUND: Among prospective cohorts of people who inject drugs (PWID),
      phylogenetic clustering of HCV infection has been observed. However, the majority
      of studies have included older PWID, representing distant transmission events.
      The aim of this study was to investigate phylogenetic clustering of HCV infection
      among a cohort of street-involved youth. METHODS: Data were derived from a
      prospective cohort of street-involved youth aged 14-26 recruited between 2005 and
      2012 in Vancouver, Canada (At Risk Youth Study, ARYS). HCV RNA testing and
      sequencing (Core-E2) were performed on HCV positive participants. Phylogenetic
      trees were inferred using maximum likelihood methods and clusters were identified
      using ClusterPicker (Core-E2 without HVR1, 90% bootstrap threshold, 0.05 genetic
      distance threshold). RESULTS: Among 945 individuals enrolled in ARYS, 16% (n=149,
      100% recent injectors) were HCV antibody positive at baseline interview (n=86) or
      seroconverted during follow-up (n=63). Among HCV antibody positive participants
      with available samples (n=131), 75% (n=98) had detectable HCV RNA and 66% (n=65,
      mean age 23, 58% with recent methamphetamine injection, 31% female, 3% HIV+) had
      available Core-E2 sequences. Of those with Core-E2 sequence, 14% (n=9) were in a
      cluster (one cluster of three) or pair (two pairs), with all reporting recent
      methamphetamine injection. Recent methamphetamine injection was associated with
      membership in a cluster or pair (P=0.009). CONCLUSION: In this study of street
      involved youth with HCV infection and recent injecting, 14% demonstrated
      phylogenetic clustering. Phylogenetic clustering was associated with recent
      methamphetamine injection, suggesting that methamphetamine drug injection may
      play an important role in networks of HCV transmission.

PMID- 25977205
TI  - Addiction and treatment experiences among active methamphetamine users recruited
      from a township community in Cape Town, South Africa: A mixed-methods study.
AB  - BACKGROUND: Since 2000, there has been a dramatic increase in methamphetamine use
      in South Africa, but little is known about the experiences of out-of-treatment
      users. This mixed-methods study describes the substance use histories, addiction
      symptoms, and treatment experiences of a community-recruited sample of
      methamphetamine users in Cape Town. METHODS: Using respondent driven sampling,
      360 methamphetamine users (44% female) completed structured clinical interviews
      to assess substance abuse and treatment history and computerized surveys to
      assess drug-related risks. A sub-sample of 30 participants completed in-depth
      interviews to qualitatively explore experiences with methamphetamine use and drug
      treatment. RESULTS: Participants had used methamphetamine for an average of 7.06
      years (SD=3.64). They reported using methamphetamine on an average of 23.49 of
      the past 30 days (SD=8.90); 60% used daily. The majority (90%) met ICD-10
      criteria for dependence, and many reported severe social, financial, and legal
      consequences. While only 10% had ever received drug treatment, 90% reported that
      they wanted treatment. In the qualitative interviews, participants reported
      multiple barriers to treatment, including beliefs that treatment is ineffective
      and relapse is inevitable in their social context. They also identified important
      motivators, including desires to be drug free and improve family functioning.
      CONCLUSION: This study yields valuable information to more effectively respond to
      emerging methamphetamine epidemics in South Africa and other low- and middle
      income countries. Interventions to increase uptake of evidence-based services
      must actively seek out drug users and build motivation for treatment, and offer
      continuing care services to prevent relapse. Community education campaigns are
      also needed.

PMID- 25977208
TI  - Identification of mannitol as compatible solute in Gluconobacter oxydans.
AB  - Gluconobacter oxydans is an industrially important bacterium owing to its regio-
      and enantio-selective incomplete oxidation of various sugars, alcohols, and
      polyols. The complete genome sequence is available, but it is still unknown how
      the organism adapts to highly osmotic sugar-rich environments. Therefore, the
      mechanisms of osmoprotection in G. oxydans were investigated. The accumulation
      and transport of solutes are hallmarks of osmoadaptation. To identify potential
      osmoprotectants, G. oxydans was grown on a yeast glucose medium in the presence
      of 100 mM potassium phosphate (pH 7.0) along with various concentrations of
      sucrose (0-600 mM final concentration), which was not metabolized. Intracellular
      metabolites were analyzed by HPLC and (13)C NMR spectroscopy under stress
      conditions. Both of these analytical techniques highlighted the accumulation of
      mannitol as a potent osmoprotectant inside the stressed cells. This intracellular
      mannitol accumulation correlated with increased extracellular osmolarity of the
      medium. For further confirmation, the growth behavior of G. oxydans was analyzed
      in the presence of small amounts of mannitol (2.5-10 mM) and 300 mM sucrose.
      Growth under sucrose-induced osmotic stress conditions was almost identical to
      control growth when exogenous mannitol was added in low amounts. Thus, mannitol
      alleviates the osmotic stress of sucrose on cellular growth. Moreover, the
      positive effect of exogenous mannitol on the rate of glucose consumption and
      gluconate formation was also monitored. These results may be helpful to optimize
      the processes of industrial product formation in highly concentrated sugar
      solutions. 

PMID- 25977207
TI  - Antibiotic Prophylaxis in Autologous Vein Graft Reconstructions of the Lower
      Extremity.
AB  - BACKGROUND: Different factors contribute to infection after arterial
      reconstructive surgery. Prophylactic antibiotic use during surgery is widespread,
      however, there is insufficient evidence to support the use of prophylactic
      antibiotics with autologous vein grafting. The aim of our study was to assess the
      effect of single-dose prophylactic antibiotics in patients undergoing autologous
      vein grafting. METHODS: Patients undergoing arterial bypass reconstruction in the
      lower extremity between 2004 and 2012 were retrospectively screened for use of
      vein grafts. Patients receiving single-dose antibiotic prophylaxis (group 1) were
      compared with those not receiving prophylaxis (group 2). RESULTS: Primary outcome
      was surgical site infection (SSI), and 142 patients were included. The SSI
      occurred in 22% of patients in group 1 and in 29% of patients in group 2 (P =
      .39; odds ratio: 1.46 confidence interval 95%: 0.61-3.47). CONCLUSIONS: Results
      showed no significant effect from single-dose antibiotic prophylaxis on lowering
      the incidence of SSI.

PMID- 25977209
TI  - Preparative scale purification of fucosyl-N-acetylglucosamine disaccharides and
      their evaluation as potential prebiotics and antiadhesins.
AB  - Fucosyl-N-acetylglucosamine disaccharides are important core structures that form
      part of human mucosal and milk glyco-complexes. We have previously shown that
      AlfB and AlfC alpha-L-fucosidases from Lactobacillus casei are able to synthesize
      fucosyl-alpha-1,3--N-acetylglucosamine (Fuc-alpha1,3-GlcNAc) and fucosyl-alpha
      1,6-N-acetylglucosamine (Fuc-alpha1,6-GlcNAc), respectively, in
      transglycosylation reactions. Here, these reactions were performed in a
      semipreparative scale, and the produced disaccharides were purified. The maximum
      yields obtained of Fuc-alpha1,3-GlcNAc and Fuc-alpha1,6-GlcNAc were 4.2 and 9.3
      g/l, respectively. The purified fucosyl-disaccharides were then analyzed for
      their prebiotic effect in vitro using strains from the Lactobacillus
      casei/paracasei/rhamnosus group and from Bifidobacterium species. The results
      revealed that 6 out of 11 L. casei strains and 2 out of 6 L. rhamnosus strains
      tested were able to ferment Fuc-alpha1,3-GlcNAc, and L. casei BL87 and L.
      rhamnosus BL327 strains were also able to ferment Fuc-alpha1,6-GlcNAc. DNA
      hybridization experiments suggested that the metabolism of Fuc-alpha1,3-GlcNAc in
      those strains relies in an alpha-L-fucosidase homologous to AlfB. Bifidobacterium
      breve and Bibidobacterium pseudocatenolatum species also metabolized Fuc-alpha1,3
      GlcNAc. Notably, L-fucose was excreted from all the Lactobacillus and
      Bifidobacterium strains fermenting fucosyl-disaccharides, except from strains L.
      rhamnosus BL358 and BL377, indicating that in these latest strains, L-fucose was
      catabolized. The fucosyl-disaccharides were also tested for their inhibitory
      potential of pathogen adhesion to human colon adenocarcinoma epithelial (HT29)
      cell line. Enteropathogenic Escherichia coli (EPEC) strains isolated from
      infantile gastroenteritis were used, and the results showed that both fucosyl
      disaccharides inhibited adhesion to different extents of certain EPEC strains to
      HT29 cells in tissue culture.

PMID- 25977206
TI  - Individualized relapse prediction: Personality measures and striatal and insular
      activity during reward-processing robustly predict relapse.
AB  - BACKGROUND: Nearly half of individuals with substance use disorders relapse in
      the year after treatment. A diagnostic tool to help clinicians make decisions
      regarding treatment does not exist for psychiatric conditions. Identifying
      individuals with high risk for relapse to substance use following abstinence has
      profound clinical consequences. This study aimed to develop neuroimaging as a
      robust tool to predict relapse. METHODS: 68 methamphetamine-dependent adults (15
      female) were recruited from 28-day inpatient treatment. During treatment,
      participants completed a functional MRI scan that examined brain activation
      during reward processing. Patients were followed 1 year later to assess
      abstinence. We examined brain activation during reward processing between
      relapsing and abstaining individuals and employed three random forest prediction
      models (clinical and personality measures, neuroimaging measures, a combined
      model) to generate predictions for each participant regarding their relapse
      likelihood. RESULTS: 18 individuals relapsed. There were significant group by
      reward-size interactions for neural activation in the left insula and right
      striatum for rewards. Abstaining individuals showed increased activation for
      large, risky relative to small, safe rewards, whereas relapsing individuals
      failed to show differential activation between reward types. All three random
      forest models yielded good test characteristics such that a positive test for
      relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood
      ratio of 0.48. CONCLUSIONS: These findings suggest that neuroimaging can be
      developed in combination with other measures as an instrument to predict relapse,
      advancing tools providers can use to make decisions about individualized
      treatment of substance use disorders.

PMID- 25977210
TI  - Priority of Lophophacidium over Canavirgella: taxonomic status of Lophophacidium
      dooksii and Canavirgella banfieldii, causal agents of a white pine needle
      disease.
AB  - In 2009 unusual white pine needle discoloration was observed in eastern Canada
      and northeastern USA. While the symptoms were similar in most pine stands, the
      disease was diagnosed as Canavirgella banfieldii in several locations and Dooks
      needle blight caused by Lophophacidium dooksii in others. Because of the
      similarities in symptom development and morphological characters of the causal
      agents, it was suspected that C. banfieldii and L. dooksii are either the same or
      closely related species. To test this hypothesis we examined several collections
      representing C. banfieldii and L. dooksii, including the two type specimens.
      Phylogenetic analyses of nuc internal transcribed spacer rDNA sequences confirm
      the synonymy of C. banfieldii with the earlier described L. dooksii and provide
      the first evidence of the close evolutionary relationship of L. dooksii to other
      pine pathogens. 

PMID- 25977211
TI  - Novel species of Botryosphaeriaceae associated with shoot blight of pistachio.
AB  - Various species of phytopathogenic Botryosphaeriaceae were identified previously
      from pistachio trees worldwide. Disease symptoms caused by pathogens in
      Botryosphaeriaceae on pistachio include panicle and shoot blight, leaf
      defoliation, fruit discoloration and decay. In this study species of
      Botryosphaeriaceae were collected from blighted pistachio shoots in Arizona, USA,
      and Greece. The aims of this study were to identify these Botryosphaeriaceae
      isolates and to test their pathogenicity to pistachio. The fungi were identified
      based on comparisons of DNA sequence data of the nuclear rDNA internal
      transcribed spacer region (ITS), a partial translation elongation factor 1-alpha
      gene (TEF1), a partial beta-tubulin gene (TUB2) and morphological
      characteristics. Results indicated that some isolates collected from pistachio
      represent two previously undescribed species, which we described here as
      Lasiodiplodia americana sp. nov. from the United States and Neofusicoccum
      hellenicum sp. nov. from Greece. Field inoculations of L. americana and N.
      hellenicum on branches of four pistachio cultivars showed that both L. americana
      and N. hellenicum are pathogenic on pistachio. The four pistachio cultivars
      differed in their susceptibility to the Botryosphaeriaceae species. Results of
      this study suggested that the two new species of Botryosphaeriaceae need to be
      monitored carefully to determine the distribution of these pathogens and the
      possible spread to other areas. 

PMID- 25977212
TI  - Action mechanism for 3beta-hydroxykaurenoic acid and 4,4-dimethylanthracene
      1,9,10(4H)-trione on Botrytis cinerea.
AB  - The mechanism of action of the diterpenoid 3beta-hydroxykaurenoic acid and the
      anthraquinone 4,4-dimethylanthracene-1,9,10(4H)-trione on the phytopathogenic
      fungus Botrytis cinerea was studied. The effect of both compounds on the
      respiratory process and on the membrane integrity of B. cinerea was evaluated.
      The results showed that 3beta-hydroxykaurenoic acid inhibited the growth of this
      fungus by disrupting the plasmatic membrane. This compound also partially
      affected oxygen consumption of B. cinerea germinating conidia. Conversely, 4,4
      dimethylanthracene-1,9,10(4H)-trione did not produce membrane disruption of B.
      cinerea. The effect of this compound on mycelial growth was notably increased by
      the presence of an inhibitor of the cyanide-resistant respiration pathway. It
      also was shown that the anthraquinone inhibited oxygen consumption by about 80%;
      therefore this compound would act as a potent inhibitor of the cytochrome pathway
      of the respiratory chain to exert its antifungal effect. 

PMID- 25977213
TI  - Phylogenetic and chemotypic diversity of Periglandula species in eight new
      morning glory hosts (Convolvulaceae).
AB  - Periglandula ipomoeae and P. turbinae (Ascomycota, Clavicipitaceae) are recently
      described fungi that form symbiotic associations with the morning glories
      (Convolvulaceae) Ipomoea asarifolia and Turbina corymbosa, respectively. These
      Periglandula species are vertically transmitted and produce bioactive ergot
      alkaloids in seeds of infected plants and ephemeral mycelia on the adaxial
      surface of young leaves. Whether other morning glories that contain ergot
      alkaloids also are infected by Periglandula fungi is a central question. Here we
      report on a survey of eight species of Convolvulaceae (Argyreia nervosa, I.
      amnicola, I. argillicola, I. gracilis, I. hildebrandtii, I. leptophylla, I.
      muelleri, I. pes-caprae) for ergot alkaloids in seeds and associated
      clavicipitaceous fungi potentially responsible for their production. All host
      species contained ergot alkaloids in four distinct chemotypes with concentrations
      of 15.8-3223.0 MUg/g. Each chemotype was a combination of four or five ergot
      alkaloids out of seven alkaloids detected across all hosts. In addition, each
      host species exhibited characteristic epiphytic mycelia on adaxial surfaces of
      young leaves with considerable interspecific differences in mycelial density. We
      sequenced three loci from fungi infecting each host: the nuclear rDNA internal
      transcribed spacer region (ITS), introns of the translation factor 1-alpha gene
      (tefA) and the dimethylallyl-tryptophan synthase gene (dmaW), which codes for the
      enzyme that catalyzes the first step in ergot alkaloid biosynthesis. Phylogenetic
      analyses confirmed that these fungi are in the family Clavicipitaceae and form a
      monophyletic group with the two described Periglandula species. This study is the
      first to report Periglandula spp. from Asian, Australian, African and North
      American species of Convolvulaceae, including host species with a shrub growth
      form and host species occurring outside of the tropics. This study demonstrates
      that ergot alkaloids in morning glories always co-occur with Periglandula spp.
      and that closely related Periglandula spp. produce alkaloid chemotypes more
      similar than more distantly related species. 

PMID- 25977214
TI  - New trichomycete species from China and additional information on Gauthieromyces.
AB  - We describe three new species of gut fungi (Kickxellomycotina, Harpellales) from
      aquatic insects, including Caudomyces typhella from a crane fly larva and
      Genistelloides torrentis and Orphella sinica from stonefly nymphs. Details on
      trichomycete species previously reported from Asia, including China, are
      provided. Recent descriptions of two new species of Gauthieromyces provide a more
      complete understanding of the genus; it is emended to reflect this new
      information and an epitype is designated. The description of G. indicus is
      emended based on an examination of the type specimen and additional collections
      of this species from China. 

PMID- 25977215
TI  - Taxonomic position of the genus Bicornispora and the appearance of a new species
      Bicornispora seditiosa.
AB  - The discovery of a second species of Bicornispora in Spain, B. seditiosa, which
      is closely related to B. exophiala but has smaller ascospores, narrower asci and
      different ecology, gave us the opportunity to culture and sequence the fungus.
      Phylogenetic analyses of rDNA regions including partial nuc 28S rDNA (28S) and
      ITS1-5.8S-ITS2 (ITS) supported a close relationship with species of the genus
      Lambertella (Rutstroemiaceae), placing Bicornispora, previously ascribed to
      Coryneliales, within Helotiales. This result confirmed an evolutionary linkage
      between certain inoperculate discomycetes such as Lambertella palmeri and derived
      cleistothecial forms (Bicornispora spp.). Based on analyses of morphological
      study and molecular phylogenetic analyses, a new combination Rutstroemia
      asphodeli is proposed for Ciboria asphodeli. 

PMID- 25977216
TI  - Inter-observer variability of response evaluation criteria for hepatocellular
      carcinoma treated with chemoembolization.
AB  - BACKGROUND: Data comparing EASL and mRECIST criteria for response evaluation in
      treatment of hepatocellular carcinoma are rare. We evaluated inter-observer
      variability by these two response evaluation criteria in treatment-naive patients
      undergoing chemoembolization. METHODS: For 133 patients undergoing
      chemoembolization, two radiologists independently measured sum of bi-dimensional
      and uni-dimensional diameters at baseline using both EASL criteria and mRECIST,
      and their changes on first follow-up for up to 5 target lesions. RESULTS:
      Concordance correlation coefficients for sum of bi-dimensional and uni
      dimensional diameters at baseline between two observers were 0.992 and 0.988,
      respectively. However, those for their changes on follow-up were 0.865 and 0.877,
      respectively. Similarly, mean differences in sum of bi-dimensional and uni
      dimensional diameters at baseline between two observers were small; -0.455 and
      0.079 cm, respectively. However, mean differences in changes (%) in sum of bi
      dimensional and uni-dimensional diameters on first follow-up between observers
      increased by -9.715% and -9.320%, respectively. Regarding tumour numbers, kappa
      value between observers was 0.942. For treatment response (complete or partial
      response, stable disease and progression), kappa-value was 0.941 by both
      criteria. When only up to two target lesions were assessed, kappa-value was 1.000
      by both criteria. CONCLUSIONS: Inter-observer agreements using both response
      evaluation criteria were excellent, especially when up to two targets were
      assessed.

PMID- 25977217
TI  - Changes in nutritional status among displaced North Korean children living in
      South Korea.
AB  - BACKGROUND: As many nations experience the nutrition transition, changes in the
      nutritional status of children moving from food insecure to food affluent
      societies has become an important, but infrequently studied, public health issue.
      AIM: To determine changes in the nutritional status of North Korean children
      after relocating to food-affluent South Korea (SK) from food-deficient North
      Korea (NK) and relationships of current nutritional status with food environment
      at birth and exposure to food affluent environments. SUBJECTS AND METHODS:
      Socioeconomic status, relocation history and anthropometric information were
      obtained from 70 NK children (6-15 years) living in SK, through questionnaires,
      interviews and direct measurements. RESULTS: Following the first 2 years in SK,
      the height and weight of NK children significantly (p = 0.000) improved, yet they
      were still shorter (p = 0.000) than SK peers, while the prevalence of obesity was
      similar to those of SK children. The likelihood of remaining stunted was
      significantly associated with older age and shorter residency in SK (p < 0.05),
      but there was no significant association with food security situation at birth.
      CONCLUSION: Even a short exposure to food affluent environments improved the
      nutritional status among children, but linear growth deficits are slow to recover
      as overall nutritional status remains poor compared to peers without exposures to
      food insecurity.

PMID- 25977218
TI  - The NLRP3-CASP1 Inflammasome Induces Glucocorticoid Resistance in ALL.
AB  - Overexpression of CASP1 and its activator NLRP3 confers glucocorticoid resistance
      in ALL. 

PMID- 25977219
TI  - CAR Signaling Domains Regulate T-Cell Exhaustion and Clinical Efficacy.

PMID- 25977220
TI  - LKB1 Inactivation Promotes ROS-Induced Plasticity in NSCLC.
AB  - LKB1 inactivation generates a redox imbalance that promotes ADC-to-SCC
      transdifferentiation in NSCLC. 

PMID- 25977221
TI  - Biofilms Enhance Metabolic Changes Associated with Colon Cancer.
AB  - Biofilms enhance production of N(1),N(12)-diacetylspermine and other polyamines
      in colon tumors. 

PMID- 25977222
TI  - Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis.
AB  - Stress induced by the accumulation of unfolded proteins in the endoplasmic
      reticulum (ER) is observed in many human diseases, including cancers. Cellular
      adaptation to ER stress is mediated by the unfolded protein response (UPR), which
      aims at restoring ER homeostasis. The UPR has emerged as a major pathway in
      remodeling cancer gene expression, thereby either preventing cell transformation
      or providing an advantage to transformed cells. UPR sensors are highly regulated
      by the formation of dynamic protein scaffolds, leading to integrated
      reprogramming of the cells. Herein, we describe the regulatory mechanisms
      underlying UPR signaling upon cell intrinsic or extrinsic challenges, and how
      they engage cell transformation programs and/or provide advantages to cancer
      cells, leading to enhanced aggressiveness or chemoresistance. We discuss the
      emerging cross-talk between the UPR and related metabolic processes to ensure
      maintenance of protein homeostasis and its impact on cell transformation and
      tumor growth. SIGNIFICANCE: ER stress signaling is dysregulated in many forms of
      cancer and contributes to tumor growth as a survival factor, in addition to
      modulating other disease-associated processes, including cell migration, cell
      transformation, and angiogenesis. Evidence for targeting the ER stress signaling
      pathway as an anticancer strategy is compelling, and novel agents that
      selectively inhibit the UPR have demonstrated preliminary evidence of preclinical
      efficacy with an acceptable safety profile.

PMID- 25977223
TI  - Tumor-Binding Allogeneic IgG Stimulates Antitumor T-Cell Responses.
AB  - Naturally occurring allogeneic IgG antibodies induce antitumor immunity and tumor
      rejection in mice. 

PMID- 25977224
TI  - Do you still have an appetite for a short DAPT trial?

PMID- 25977225
TI  - Clinical outcomes of first- and second-generation drug-eluting stents in patients
      undergoing rotational atherectomy for heavily calcified coronary lesions.
AB  - BACKGROUND: There is paucity of data regarding the clinical outcome of second
      generation drug- eluting stents (DES) post rotational atherectomy (RA) for
      heavily calcified coronary lesions (HCCL). METHODOLOGY: The study cohort
      comprised 99 (116 lesions) consecutive patients who underwent RA for HCCL at our
      institution and received either a first generation DES (40 patients, 53 lesions)
      or a second generation DES (59 patients, 63 lesions). The analyzed clinical
      parameters were the 12-month rates of death (all cause and cardiac), Q-wave MI,
      target lesion revascularization (TLR), definite stent thrombosis (ST) and major
      adverse cardiac events (MACE) defined as the composite of death, Q-wave MI, or
      TLR. RESULTS: The two groups were well matched for their baseline characteristics
      except for a lower left ventricular ejection fraction in the second generation
      DES group (46.0+/-23.0% vs. 55.0+/-9.0%; p=0.02). The group receiving second
      generation DES had more type C lesions (81.0% vs. 58.8%; p=0.01), shorter stent
      length (19.9+/-6.1 mm vs. 22.7+/-7.3 mm; p=0.04) and was more likely to undergo
      stent postdilatation (52.4% vs. 23.1%; p=0.001). The 1-year analyzed clinical
      parameters were similar in the two groups: all cause death (8.5% vs. 10.3%;
      p=1.0), cardiac death (8.5% vs. 2.5%; p=0.40), Q-wave MI (0% vs. 0%), TLR (3.6%
      vs. 2.7%; p=1.0), ST (0% vs. 0%), and MACE (11.9% vs. 12.8%; p=1.0). The 1-year
      MACE-free survival rate was also similar in the two cohorts. CONCLUSION: The use
      of second generation DES, following RA for HCCL, is associated with similar short
      and long-term clinical outcomes to first generation DES.

PMID- 25977226
TI  - Safety and efficacy of everolimus-eluting stents for bare-metal in-stent
      restenosis.
AB  - OBJECTIVE: The aim of this study was to compare the safety and efficacy of the
      everolimus-eluting stents (EES) with the paclitaxel-eluting stent (PES) and
      sirolimus-eluting stent (SES) for the treatment of bare-metal in-stent
      restenosis. BACKGROUND: The optimal treatment for bare-metal in-stent restenosis
      remains controversial. METHODS: The study cohort comprised 322 consecutive
      patients (543 lesions) who presented with bare-metal in-stent restenosis to our
      institution and underwent coronary artery stent implantation with EES (114
      patients; 181 lesions), PES (65 patients; 116 lesions) and SES (143 patients; 246
      lesions). The analyzed clinical parameters were the 1-year rates of death, Q-wave
      myocardial infarction (MI), target lesion revascularization (TLR), target vessel
      revascularization (TVR), definite stent thrombosis (ST) and major adverse cardiac
      events (MACE) defined as the composite of death, MI, or TLR at 1-year. RESULTS:
      The three groups were well matched for the conventional risk factors except for
      age and chronic kidney disease. The 1-year analyzed clinical parameters were
      similar in the three groups: death (EES=3.5%, PES=4.6%, SES=4.2%; p=0.94), MI
      (EES=3.5%, PES=6.3%, SES=2.1%; p=0.31), TLR (EES=9.8%, PES=9.5%, SES=5.7%;
      p=0.42), TVR (EES=14.3%, PES=11.1%, SES=11.3%; p=0.74), definite ST (EES=0.9%,
      PES=3.1%, SES=3.5%; p=0.38) and MACE (EES=14.0%, PES=15.4%, SES=10.5%; p=0.54).
      Male gender (hazard ratio=0.47; 95% confidence interval=0.25-0.88) and number of
      treated lesions (hazard ratio=1.47; 95% confidence interval=1.06-2.05) were found
      to be independent predictors of MACE. CONCLUSION: The results of the present
      study indicate that EES may provide similar safety and efficacy as first
      generation DES for the treatment of patients presenting with bare-metal in-stent
      restenosis.

PMID- 25977227
TI  - The Instantaneous wave-Free Ratio (iFR) pullback: a novel innovation using
      baseline physiology to optimise coronary angioplasty in tandem lesions.
AB  - Coronary intervention is increasingly performed in complex disease with tandem
      and diffuse disease. Pressure wires enable detailed assessment of the
      physiological significance of a stenosis but in the presence of tandem disease,
      predicting the impact of a stenting a given stenosis can be difficult and is
      impeded by flow interaction between stenoses under hyperemia. In this review, we
      consider the physiological difficulties posed by flow interaction under hyperemia
      and consider alternative approaches such as assessment under baseline conditions.
      Specifically we consider the potential value of the iFR-Pullback approach and its
      capacity to enable Virtual-PCI, which may assist in planning intervention. 

PMID- 25977228
TI  - It is not just IMRT: Human papillomavirus related oropharynx squamous cell
      carcinoma is associated with better swallowing outcomes after definitive
      chemoradiotherapy.
AB  - OBJECTIVES: Long term swallowing dysfunction in patients with oropharynx squamous
      cell carcinoma (OPSCC) treated with concurrent chemoradiation (CRT) is declining.
      While the use of intensity modulated radiotherapy (IMRT) is commonly believed to
      be a potential cause, we hypothesize that the increasing incidence of human
      papillomavirus (HPV) related disease may also favorably impact this outcome.
      MATERIALS AND METHODS: We reviewed 130 HPV+ and 17 HPV- patients with stage III
      IV OPSCC treated exclusively with conventional 3-field radiotherapy with
      chemotherapy between 2002 and 2010. The rates of normal diet, limited diet
      (significant restrictions in the types of foods eaten, and/or requiring
      nutritional supplementation for weight maintenance) and feeding tube dependence
      (FTD) were compared between HPV+ and HPV- patients. Cox proportional hazards
      modeling were used to perform univariate analysis (UVA) to examine predictors of
      a combined endpoint of dietary limitation, which included limited diet and/or
      FTD. These outcomes were also compared to our previously reported cohort of OPSCC
      patients treated between 1989 and 2002 to assess changes in toxicity over time
      given the changing disease epidemiology, in the setting of identical treatment
      regimens. RESULTS: With a median follow-up of 55 months, HPV+ patients more
      frequently had resumed a normal diet (87% vs. 65%) at last follow up and had
      lower rates of limited diet (9% vs. 18%) and FTD (4% vs. 18%) compared to HPV-
      patients (p=0.02). HPV status was the only significant predictor of reduced
      swallowing dysfunction on UVA (HR 0.19; p=0.008). When compared to our 1989-2002
      cohort, patients treated between 2002 and 2010 had less FTD (7.5% vs. 34%,
      p<0.001) and dietary limitations (26% vs.46%, p<0.001) at 6 months post
      treatment. CONCLUSIONS: HPV+ patients with OPSCC have reduced late swallowing
      dysfunction after chemoradiation compared to HPV- patients. The changing
      epidemiology of OPSCC may play a role in toxicity reduction in these patients,
      independent of the increasing use of IMRT.

PMID- 25977229
TI  - Performance of Busulfan Dosing Guidelines for Pediatric Hematopoietic Stem Cell
      Transplant Conditioning.
AB  - Achievement of a busulfan area-under-the-concentration versus time curve (AUC) of
      900 to 1500 MUM.min is associated with improved hematopoietic stem cell
      transplant (HSCT) outcomes. Multiple pediatric busulfan dosing guidelines aim to
      achieve this target. The authors' objective was to describe the AUCs achieved
      after simulated dosing using available pediatric i.v. busulfan dosing guidelines.
      The health records of children who received i.v. busulfan for HSCT conditioning
      at The Hospital for Sick Children were reviewed. Busulfan AUCs were calculated
      for each patient based on plasma busulfan concentrations using either a 1
      compartment model or a validated limited-sampling strategy. Published pediatric
      busulfan dosing guidelines were identified. Initial busulfan doses were
      determined for all patients using each dosing guideline and total body weight
      (TBW). For overweight patients (TBW-to-ideal body weight [IBW] >= 1.25), initial
      busulfan doses were also determined using IBW and adjusted IBW (IBWadj). The
      resulting AUCs were simulated. The proportion of subjects (TBW/IBW < 1.25,
      TBW/IBW >= 1.25, and infants) with an AUC within target (900 to 1500 MUM.min)
      after dosing simulation with each guideline was compared. One hundred eleven
      children (mean age, 6.2 years [SD, +/-5.2]) who received i.v. busulfan were
      included. When dosing with each of the 12 i.v. busulfan dosing guidelines
      identified was simulated using TBW in 97 non-overweight patients, the proportion
      of patients with an AUC within the target range varied from 51% to 74% and from
      45% to 64% in infants. Use of IBW or IBWadj to calculate initial busulfan doses
      in overweight children improved the performance of most guidelines. Current
      busulfan dosing guidelines vary in their ability to achieve AUCs within the
      target range. For children who are not overweight, we recommend 1 of 3 high
      performing guidelines that allow individualization of the target busulfan AUC.
      Use of either IBW or IBWadj in overweight children improves the performance of
      most guidelines. Regardless of the guideline used, therapeutic drug monitoring is
      essential to verify achievement of the target AUC. 

PMID- 25977231
TI  - The anti-inflammatory selective melanocortin receptor subtype 4 agonist, RO27
      3225, fails to prevent acoustic trauma-induced tinnitus in rats.
AB  - In preliminary studies we have observed a massive microglial activation in the
      cochlear nucleus following acoustic trauma-induced tinnitus in rats, which
      suggests that inflammatory responses within the central auditory system may be
      involved in the development and maintenance of tinnitus. Recently, the anti
      inflammatory properties of melanocortins (MCs), have gained increasing interest
      in pharmacology due to their promising therapeutic potential in the treatment of
      inflammatory-mediated diseases. Among the five subtypes of the MC receptor, MC3
      and MC4 receptors are the predominant brain receptors and are thought to play an
      important role in brain inflammation and neuroprotection. Importantly, MC4
      receptors have been found in the mouse and rat central auditory systems. In this
      study we investigated whether the MC4 receptor agonist, RO27-3225, injected s.c
      at a dose of 90 or 180ug/kg, 30min before acoustic trauma and then every 12h for
      10 days, could prevent the development of acoustic trauma-induced tinnitus in
      rats, using a conditioned behavioural suppression model. Although evidence of
      tinnitus developed in the exposed-vehicle group compared to the sham-vehicle
      group (P<=0.03), in response to a 32kHz tone, there were no significant drug
      effects from treatment with RO27-3225, indicating that it did not confer any
      protection against the development of tinnitus in this animal model. This result
      suggests that the anti-inflammatory effects of MC4 receptor agonists may not be
      sufficient to prevent tinnitus. 

PMID- 25977230
TI  - Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host
      Disease.
AB  - The relationship between intestinal microbiota composition and acute graft-versus
      host disease (GVHD) after allogeneic blood/marrow transplantation (allo-BMT) is
      not well understood. Intestinal bacteria have long been thought to contribute to
      GVHD pathophysiology, but recent animal studies in nontransplant settings have
      found that anti-inflammatory effects are mediated by certain subpopulations of
      intestinal commensals. Hypothesizing that a more nuanced relationship may exist
      between the intestinal bacteria and GVHD, we evaluated the fecal bacterial
      composition of 64 patients 12 days after BMT. We found that increased bacterial
      diversity was associated with reduced GVHD-related mortality. Furthermore,
      harboring increased amounts of bacteria belonging to the genus Blautia was
      associated with reduced GVHD lethality in this cohort and was confirmed in
      another independent cohort of 51 patients from the same institution. Blautia
      abundance was also associated with improved overall survival. We evaluated the
      abundance of Blautia with respect to clinical factors and found that loss of
      Blautia was associated with treatment with antibiotics that inhibit anaerobic
      bacteria and receiving total parenteral nutrition for longer durations. We
      conclude that increased abundance of commensal bacteria belonging to the Blautia
      genus is associated with reduced lethal GVHD and improved overall survival. 

PMID- 25977232
TI  - Gemigliptin improves renal function and attenuates podocyte injury in mice with
      diabetic nephropathy.
AB  - Podocytes participate in the formation and regulation of the glomerular
      filtration barrier. Loss of podocytes occurs during the early stages of diabetic
      nephropathy and impairs glomerular filtration. Dipeptidyl peptidase-4 (DPP-4)
      inhibitors are widely used as anti-diabetic agents in clinical practice. In this
      study, we showed that gemigliptin, a novel DPP-4 inhibitor, reduced podocyte
      apoptosis in type 2 diabetic db/db mice without reducing hyperglycemia.
      Gemigliptin (100mg/kg/day) was administered orally for 12 weeks in db/db mice.
      Blood glucose levels and albuminuria were measured. The renal cortex was
      collected for histological examination, and molecular assays were used to detect
      8-hydroxydeoxyguanosine, advanced oxidation protein products (AOPP), the receptor
      for advanced glycation end products (RAGE), and integrin-linked kinase (ILK).
      Type 2 diabetic db/db mice exhibited albuminuria, renal histopathological
      changes, and podocyte loss. Administration of gemigliptin to db/db mice
      suppressed albuminuria, enzyme activity and expression of DPP-4, and podocyte
      apoptosis. The effect of gemigliptin on diabetes-induced podocyte loss was
      associated with the suppression of oxidative damage, AOPP accumulation, RAGE
      expression, and ILK expression. These results indicate the possible benefits of
      using gemigliptin in diabetes patients to treat renal impairment without
      affecting glycemic control. 

PMID- 25977234
TI  - Prince Charles delayed regulation of herbal medicines.

PMID- 25977233
TI  - Predischarge Transthoracic Echocardiography after Surgery for Congenital Heart
      Disease: A Routine with a Reason?
AB  - BACKGROUND: Predischarge (pre-d/c) transthoracic echocardiography (TTE) is
      routine after surgery for congenital heart disease, but how it affects clinical
      care is unknown. The aim of this study was to test the hypothesis that pre-d/c
      TTE frequently reveals findings associated with short-term clinical course
      through a systematic review of findings on pre-d/c TTE and clinical events that
      followed. METHODS: Clinical outcomes of mortality, hospitalization,
      catheterization, and surgery at 1 year were examined for pediatric patients
      undergoing pre-d/c TTE between June 2010 and June 2012. Using logistic
      regression, a multivariate model was generated associating clinical, pre-d/c
      transthoracic echocardiographic, and demographic variables with unplanned
      postdischarge cardiac events (UCEs) within 1 year. RESULTS: Of 462 patients who
      underwent pre-d/c TTE, there were 265 male patients (57%) and 197 female patients
      (43%); the median age was 0.8 years (range, 0-33 years). Two hundred thirty-seven
      patients (51%) had findings (valve regurgitation, hemodynamic obstruction,
      ventricular dysfunction, unintended shunt, or pericardial effusion) on pre-d/c
      TTE, 57 of which were of more than mild severity. Agreement between pre-d/c TTE
      and postoperative transesophageal echocardiographic findings was only fair to
      moderate (kappa = 0.27-0.43). Sixty-four patients (14%) had UCEs. Univariate
      analysis revealed that UCE were more frequent in patients with diagnoses and
      surgical procedures of high complexity. After accounting for these confounding
      nonechocardiographic variables, pre-d/c transthoracic echocardiographic findings,
      specifically valve regurgitation of more than mild severity, and ventricular
      dysfunction and obstructions of any severity were independently associated with
      UCEs (odds ratios, 1.90, 1.99, and 1.85, respectively). CONCLUSIONS: Findings on
      pre-d/c TTE are frequent, commonly discordant with postoperative transesophageal
      echocardiographic results, and associated with adverse clinical events after
      surgery for congenital heart disease. These data would strongly support the
      practice of pre-d/c TTE after surgery for congenital heart disease.

PMID- 25977235
TI  - OsHrd3 is necessary for maintaining the quality of endoplasmic reticulum-derived
      protein bodies in rice endosperm.
AB  - Large amounts of seed storage proteins (SSPs) are produced in the maturing
      endosperm of rice seeds. Rice SSPs are synthesized as secretory proteins on the
      rough endoplasmic reticulum (ER), and are transported and deposited into protein
      complexes called protein bodies (PB-I and PB-II). Due to the high production of
      SSPs, unfolded SSPs may be generated during this process. However, it was
      previously unclear how such unfolded proteins are selected among synthesized
      products and removed from the ER to maintain protein quality in the endosperm.
      Since Hrd3/SEL1L recognizes unfolded proteins in yeast and mammalian protein
      quality control systems, the role of OsHrd3 in protein quality control in rice
      endosperm was investigated. Co-immunoprecipitation experiments demonstrated that
      OsHrd3 interacts with components of the Hrd1 ubiquitin ligase complex such as
      OsOS-9 and OsHrd1 in rice protoplasts. Endosperm-specific suppression of OsHrd3
      in transgenic rice reduced the levels of polyubiquitinated proteins and resulted
      in unfolded protein responses (UPRs) in the endosperm, suggesting that OsHrd3
      mediated polyubiquitination plays an important role in ER quality control. It was
      found that a cysteine-rich 13kDa prolamin, RM1, was polyubiquitinated in wild
      type (WT) seeds but not in OsHrd3 knockdown (KD) seeds. RM1 formed aberrant
      aggregates that were deposited abnormally in OsHrd3 KD seeds, resulting in
      deformed PB-I. Therefore, the quality of protein bodies is maintained by
      polyubiquitination of unfolded SSPs through the Hrd1 ubiquitin ligase system in
      rice endosperm. 

PMID- 25977236
TI  - Accumulation of extra-chloroplastic triacylglycerols in Arabidopsis seedlings
      during heat acclimation.
AB  - Heat acclimation enables plants to tolerate and survive short-term heat stress on
      hot days. In Arabidopsis thaliana, a genetically programmed heat shock response
      can be rapidly triggered in the temperature range of 32-38 degrees C through
      activation of heat shock transcription factors (HSF). The heat shock response
      leads to heat acclimation and confers short-term protection against temperatures
      above 40 degrees C. However, little is known about metabolic adjustments during
      heat acclimation.Untargeted metabolite analyses of A. thaliana seedlings revealed
      that levels of polyunsaturated triacylglycerols (TG) rapidly and dramatically
      increase during heat acclimation. TG accumulation was found to be temperature
      dependent in a temperature range of 32-50 degrees C (optimum at 42 degrees C) and
      reversible after a return from 37 degrees C to normal growth temperatures. Heat
      induced TGs accumulated in extra-chloroplastic compartments and increased in both
      roots and shoots to a similar extent. Analysis of mutants deficient in all four
      HSFA1 master regulator genes or the HSFA2 gene revealed that TG accumulation was
      not dependent on HSFs. Moreover, the TG response was not limited to heat stress
      because drought and salt stress also triggered an accumulation of TGs, but not
      short-term osmotic, cold, and high light stress. Lipid analysis revealed that
      heat-induced accumulation of TGs was not due to massive de novo fatty acid
      synthesis. It is hypothesized that TGs serve as transient stores for fatty acids
      that may be required for membrane remodelling during heat acclimation. 

PMID- 25977237
TI  - Outcomes of cochlear implanted children with cerebral palsy: A holistic approach.
AB  - OBJECTIVE: Analyze the progress of hearing and language in a group of children
      with cerebral palsy (CP) who have received cochlear implants (CI) and compare
      their progress in the clinical and functional domains. METHODS: This is a
      prospective transdisciplinary study developed within a tertiary referral center,
      with a group of nine cochlear-implanted children with CP, two- to seven-year-old.
      The assessments undertaken included audiological, language, and communication
      assessments complemented by the assessment of functional abilities and the level
      of independence as evaluated by the Pediatric Evaluation of Disability Inventory
      (PEDI) and Gross Motor Function Classification System (GMFCS). RESULTS: The
      outcomes varied, as two children achieved hearing comprehension in open-set
      evaluations. These children presented the same type of CP, athetosis, but with
      different functional skills and GMFCS levels. Only one of the subjects had any
      spoken language at the single-word level. CONCLUSIONS: A holistic view of change
      and development is central to understanding progress made in children with CP who
      received cochlear implants (CI). The functional evaluation of these children with
      CP is a useful tool for monitoring their progress and measuring their outcomes
      with CI.

PMID- 25977238
TI  - Annotation of Sequence Variants in Cancer Samples: Processes and Pitfalls for
      Routine Assays in the Clinical Laboratory.
AB  - As DNA sequencing of multigene panels becomes routine for cancer samples in the
      clinical laboratory, an efficient process for classifying variants has become
      more critical. Determining which germline variants are significant for cancer
      disposition and which somatic mutations are integral to cancer development or
      therapy response remains difficult, even for well-studied genes such as BRCA1 and
      TP53. We compare and contrast the general principles and lines of evidence
      commonly used to distinguish the significance of cancer-associated germline and
      somatic genetic variants. The factors important in each step of the analysis
      pipeline are reviewed, as are some of the publicly available annotation tools.
      Given the range of indications and uses of cancer sequencing assays, including
      diagnosis, staging, prognostication, theranostics, and residual disease
      detection, the need for flexible methods for scoring of variants is discussed.
      The usefulness of protein prediction tools and multimodal risk-based or Bayesian
      approaches are highlighted. Using TET2 variants encountered in hematologic
      neoplasms, several examples of this multifactorial approach to classifying
      sequence variants of unknown significance are presented. Although there are still
      significant gaps in the publicly available data for many cancer genes that limit
      the broad application of explicit algorithms for variant scoring, the elements of
      a more rigorous model are outlined. 

PMID- 25977239
TI  - [Not Available].

PMID- 25977240
TI  - Development and Validation of an HPLC-DAD Analysis for Flavonoids in the gel of
      Scutia buxifolia.
AB  - Recent interest in flavonoids has increased greatly due to their biological and
      pharmacological activities. Flavonoids consist of a large group of low molecular
      weight polyphenolic substances, naturally occurring in fruits, vegetables and
      tea, and are an integral part of the human diet. Quercetin and rutin are
      bioactive markers of Scutia buxifolia and no analytical methods reported so far,
      associated with quality control of polyherbal formulations containing this
      species. Therefore, there is a need to develop a sensitive, simple, rapid and
      reliable method that can simultaneously determine these markers in their
      combinations. A high-performance liquid chromatography method has been developed
      and validated as per ICH guidelines. The chromatographic analysis was performed
      using a C18 column, the mobile phase system consisted of acetonitrile-water (70 :
      30, v/v) containing 0.5% (v/v) phosphoric acid and quercetin and rutin were
      quantificadoa to 356 nm. The proposed method for the quantification of quercetin
      and rutin in the S. buxifolia fraction (EaSb) and gel was linear, sensitive,
      precise, specific, accurate and robust. This validated method can be used to
      control the quality of the EaSb and the gel. 

PMID- 25977242
TI  - Long-term disease course in a patient with severe neonatal IPEX syndrome.
AB  - We report here on the clinical, histological and immunological findings regarding
      a patient with immunodysregulation polyendocrinopathy enteropathy X-linked
      syndrome who was treated for the first 21 years with a combination of
      immunosuppressant agents (IS). The potential modalities of care and treatment
      options in this rare and severe immune-mediated disorder are discussed. So, long
      term outcome for IPEX patients can be obtained with immunosuppressive treatment,
      which is important since the outcome of haematopoietic stem cell transplantation
      for this population is variable.

PMID- 25977243
TI  - Biography: Hagiography or demonology?

PMID- 25977241
TI  - Safety, efficacy and indications of prescription of maraviroc in clinical
      practice: Factors associated with clinical outcomes.
AB  - Maraviroc is approved for treatment-experienced HIV+ adults in twice-daily
      administration. Limited data are available on safety, efficacy and use in routine
      clinical practice, outside of restrictive clinical trials. This retrospective
      multicenter (27 centers) study included 667 subjects starting a regimen with
      maraviroc. The primary endpoint was plasma HIV-RNA <50copies/mL and CD4(+) cell
      count change at 48 and 96weeks (FDA snapshot analysis). 94.4% had CCR5 tropism
      (58.3% TrofileTM, 29.2% population genotype, and 12% genotyping proviral DNA).
      Half of the subjects received the drug in scenarios or dosages outside the
      initial approval. Maraviroc was prescribed for salvage in 346 (51.9%)
      individuals, as a switch strategy due to toxicity in 135 (38.7%), for immune
      discordance in 75 (11.2%), and for simplification in 48 (7.2%). After salvage
      therapy, 223 (64.5%) subjects had HIV-RNA <50copies/mL at 48weeks, and 178
      (51.4%) at 96weeks. Darunavir/r was included in 224 (64.7%) subjects and
      associated with higher rates of virological and immunologic efficacy (p<0.001).
      In multivariate analysis MSM (OR 2.25; 95%CI 1.29-3.94) and baseline HIV-RNA
      <100,000copies/mL (OR 1.96; 1.06-3.70) were associated with virological
      suppression. An increase in CD4(+) counts was seen at 48 and 96weeks in subjects
      with immune discordance (p<0.001). Maraviroc was used once-daily in 142 (21.3%)
      subjects overall, and 68 (57.4%) in switch/simplification. No new safety signals
      were identified. Besides in salvage regimens, maraviroc was frequently used in
      switch due to toxicity, simplification, and immune discordance. The efficacy in
      salvage in clinical practice was higher than in phase III clinical trials, likely
      due to availability of new active drugs in the regimen. These results increase
      our understanding of the efficacy, safety, and conditions of prescription of
      maraviroc beyond the initial registrational trials and the early manufacturer
      pharmacovigilance programs. 

PMID- 25977245
TI  - An interview with Mark Graber.

PMID- 25977246
TI  - The American College of Surgeons National Surgical Quality Improvement Program:
      achieving better and safer surgery.
AB  - BACKGROUND: The American College of Surgeons (ACS) National Surgical Quality
      Improvement Program (NSQIP), in operation since late 2004, evaluates surgical
      quality and safety by feeding back valid, timely, risk-adjusted outcomes, which
      providers use to improve care. METHODS: A number of components have been
      developed and refined in the more than a decade since ACS NSQIP's initiation.
      These items can be grouped into areas of data collection, case sampling, risk
      adjustment, feedback reporting, the expansion into procedure-targeted sampling,
      development of improvement collaboratives, and the development of improvement
      tools. Although ACS NSQIP was originally designed as a hospital-based program, it
      now also allows for surgeon-specific reporting that can be used by individual
      surgeons as a feedback tool to improve their performance. RESULTS: There are more
      than 600 ACS NSQIP hospitals in 49 of the 50 states of the United States and in
      13 other countries. Virtually all surgical (sub)specialties are touched by ACS
      NSQIP, which contains several million patient records and more than 100
      statistically risk-adjusted models. In studies that have used ACS NSQIP clinical
      data, demonstrable improvement has been reported in local hospitals, in regional
      collaboratives, and across the program overall. Concomitantly, substantial cost
      savings for individual hospitals, as well as at regional and national levels,
      have been reported. CONCLUSION: ACS NSQIP has not only demonstrated how and why
      the use of accurate clinical data is crucial, but also how the program, through
      its risk-adjusted feedback, improvement tools, and hospital collaboratives, helps
      hospitals and providers to achieve safer surgery and better patient care.

PMID- 25977247
TI  - Methods for reducing sepsis mortality in emergency departments and inpatient
      units.
AB  - BACKGROUND: As part of a zero-tolerance approach to preventable deaths, North
      Shore-LIJ Health System (North Shore-LIJ) leadership prioritized a major patient
      safety initiative to reduce sepsis mortality in 2009 across 10 acute care
      hospitals (an 11th joined later). At baseline (2008), approximately 3,500
      patients were discharged with a diagnosis of sepsis, which ranked as the top All
      Patient Refined Diagnosis-Related Group by number of deaths (N = 883). Initially,
      the focus was sepsis recognition and treatment in the emergency departments
      (EDs). METHODS: North Shore-LIJ, the 14th largest health care system in the
      United States, cares for individuals at every stage of life at 19 acute care and
      specialty hospitals and more than 400 outpatient physician practice sites
      throughout New York City and the greater New York metropolitan area. The health
      system launched a strategic partnership with the Institute for Healthcare
      Improvement (IHI) in August 2011 to accelerate the pace of sepsis improvement.
      Throughout the course of the initiative, North Shore-LIJ collaborated with many
      local, state, national, and international organizations to test innovative ideas,
      share evidence-based best practices, and, more recently, to raise public
      awareness. RESULTS: North Shore-LIJ reduced overall sepsis mortality by
      approximately 50% in a six-year period (2008-2013; sustained through 2014) and
      increased compliance with sepsis resuscitation bundle elements in the EDs and
      inpatient units in the 11 acute care hospitals. CONCLUSION: Improvements were
      achieved by engaging leadership; fostering interprofessional collaboration,
      collaborating with other leading health care organizations; and developing
      meaningful, real-time metrics for all levels of staff.

PMID- 25977248
TI  - Emergency manual implementation: can brief simulation-based or staff trainings
      increase familiarity and planned clinical use?
AB  - BACKGROUND: Emergency manuals (EMs)-context-relevant sets of cognitive aids such
      as crisis checklists-are useful tools to enhance perioperative patient care.
      Studies in high-hazard industries demonstrate that humans, regardless of
      expertise, do not optimally retrieve or deploy key knowledge under stress. EM use
      has been shown in both health care simulation studies and other industries to
      help expert teams effectively manage critical events. However, clinical adoption
      and use are still nascent in health care. Recognizing that training with, access
      to, and cultural acceptance of EMs can be vital elements for successful
      implementation, this study assessed the impact of a brief in situ operating room
      (OR) staff training program on familiarity with EMs and intention to use them
      during critical events. METHODS: Nine 50-minute training sessions were held with
      OR staff as part of a broader perioperative EM implementation. Participants
      primarily included OR nurses and surgical technologists. The simulation-based in
      situ trainings included why and how to use EMs, familiarization with format,
      simulated scenarios of critical events, and debriefings. A retrospective pre-post
      survey was conducted to determine participants' levels of EM familiarity and
      intentions to use EMs clinically. RESULTS: The 126 trained OR staff self-reported
      increases in awareness of the EM (p < .01), familiarity with EM (p < .01),
      willingness to use for educational review (p < .01), and intention to use during
      critical events (p < .01). Participants rated the sessions highly and expressed
      interest in more opportunities to practice using EMs. CONCLUSIONS: Implementing
      institutions should not only provide EMs in accessible places in ORs but also
      incorporate training mechanisms to increase clinicians' familiarity, cultural
      acceptance, and planned clinical use.

PMID- 25977250
TI  - Information gaps in newborn care and their potential for harm.
AB  - BACKGROUND: Access to complete and correct patient information is vital for
      physicians to make appropriate patient care decisions and to avoid medical
      errors. However, the perinatal period represents a unique situation in which care
      of the fetus is initiated by an obstetrician and then assumed by either a
      pediatrician or a family practice physician after birth. This often abrupt
      handoff of care has the potential to result in an inadequate transfer of
      information and significant gaps in care. A study was conducted to determine the
      presence and extent of information gaps in newborn care. METHODS: Maternal
      demographics and history, and results of all prenatal laboratory tests, were
      obtained from maternal interviews and medical records. The collected data were
      compared with information in infant medical records. A positive maternal history
      not documented in the infant medical record was counted as an information gap.
      RESULTS: Of 72 enrolled mother-infant dyads, nearly all (71 [99%]) of mothers had
      at least one positive history in the areas reviewed, and 59 (82%) newborn charts
      had one or more information gaps. Thirty-eight (53%) newborn charts had one of
      two or fewer information gaps, and 17 (24%) had four or more information gaps.
      None of the infants with a maternal history of depression, positive family
      history of an infectious disease, potentially inheritable genetic disorder, or
      family history of phototherapy or exchange transfusion had these documented in
      their medical records. CONCLUSIONS: The results of this study suggest that
      significant information gaps are common in newborn care at birth and may have the
      potential for an adverse impact on the care and outcomes of the newborn.
      Obtaining a history directly from the parents rather than relying on maternal
      medical records may minimize or eliminate these information gaps and thus improve
      newborn care.

PMID- 25977249
TI  - Use of a glucose management service improves glycemic control following vascular
      surgery: an interrupted time-series study.
AB  - BACKGROUND: The optimal method for obtaining good blood glucose control in
      noncritically ill patients undergoing peripheral vascular surgery remains a topic
      of debate for surgeons, endocrinologists, and others involved in the care of
      patients with peripheral arterial disease and diabetes. A prospective trial was
      performed to evaluate the impact of routine use of a glucose management service
      (GMS) on glycemic control within 24 hours of lower-extremity revascularization
      (LER). METHODS: In an interrupted time-series design (May 1, 2011-April 30,
      2012), surgeon-directed diabetic care (Baseline phase) to routine GMS involvement
      (Intervention phase) was compared following LER. GMS assumed responsibility for
      glucose management through discharge. The main outcome measure was glycemic
      control, assessed by (1) mean hospitalization glucose and (2) the percentage of
      recorded glucose values within target range. Statistical process control charts
      were used to assess the impact of the intervention. RESULTS: Clinically important
      differences in patient demographics were noted between groups; the 19 patients in
      the Intervention arm had worse peripheral vascular disease than the 19 patients
      in the Baseline arm (74% critical limb ischemia versus 58%; p = .63). Routine use
      of GMS significantly reduced mean hospitalization glucose (191 mg/dL Baseline
      versus 150 mg/dL Intervention, p < .001). Further, the proportion of glucose
      values in target range increased (48% Baseline versus 78% Intervention, p = .05).
      Following removal of GMS involvement, measures of glycemic control did not
      significantly decrease for the 19 postintervention patients. CONCLUSIONS: Routine
      involvement of GMS improved glycemic control in patients undergoing LER. Future
      work is needed to examine the impact of improved glycemic control on clinical
      outcomes following LER.

PMID- 25977251
TI  - Personal protective equipment and simulation: use of chemiluminescent glow sticks
      as a game changer?

PMID- 25977252
TI  - A two-way street: what the United States can learn from resource-limited
      countries to improve health care delivery and reduce costs.

PMID- 25977253
TI  - Association between FOXP3 polymorphisms and susceptibility to autoimmune
      diseases: A meta-analysis.
AB  - OBJECTIVE: The aim of this study was to explore whether the FOXP3 -3279 A/C
      polymorphism and (GT)n microsatellite polymorphisms are associated with
      susceptibility to autoimmune diseases. METHODS: A meta-analysis was conducted on
      the associations between the FOXP3 -3279 A/C polymorphism and (GT)15 and (GT)16
      polymorphisms and autoimmune diseases. RESULTS: Twenty-two comparative studies
      with a total of 7962 patients and 7453 controls were included in the meta
      analysis. Meta-analysis revealed an association between autoimmune disease and
      the FOXP3 -3279 AA + AC genotype (OR = 1.480, 95% CI = 1.263-1.614, p < 1.0 * 10(
      9)), and stratification by ethnicity indicated a significant association between
      the FOXP3 -3279 AA + AC genotype and autoimmune diseases in Asians (OR = 1.416,
      95% CI = 1.225-1.637, p = 2.5 * 10(-7)) and non-Caucasians (OR = 1.432, 95% CI =
      1.245-1.647, p = 7.5 * 10(-8)). In addition, corrected p values for multiple
      testing remained significant. Meta-analysis revealed no association between
      autoimmune disease and the FOXP3 (GT)15 allele (OR = 1.051, 95% CI = 0.933-1.183,
      p = 0.413). Similarly, the FOXP3 (GT)16 allele showed no associations with
      autoimmune disease. CONCLUSIONS: This meta-analysis indicates that the FOXP3 
      3279 A/C polymorphism is associated with susceptibility to autoimmune disease in
      Asians and non-Caucasians.

PMID- 25977254
TI  - Can mechanistic explanation be reconciled with scale-free constitution and
      dynamics?
AB  - This paper considers two objections to explanations that appeal to mechanisms to
      explain biological phenomena. Marom argues that the time-scale on which many
      phenomena occur is scale-free. There is also reason to suspect that the network
      of interacting entities is scale-free. The result is that mechanisms do not have
      well-delineated boundaries in nature. I argue that bounded mechanisms should be
      viewed as entities scientists posit in advancing scientific hypotheses. In
      positing such entities, scientists idealize. Such idealizations can be highly
      productive in developing and improving scientific explanations even if the
      hypothesized mechanisms never precisely correspond to bounded entities in nature.
      Mechanistic explanations can be reconciled with scale-free constitution and
      dynamics even if mechanisms as bounded entities don't exist. 

PMID- 25977255
TI  - Respiratory chain protein turnover rates in mice are highly heterogeneous but
      strikingly conserved across tissues, ages, and treatments.
AB  - The mitochondrial respiratory chain (RC) produces most of the cellular ATP and
      requires strict quality-control mechanisms. To examine RC subunit proteostasis in
      vivo, we measured RC protein half-lives (HLs) in mice by liquid chromatography
      tandem mass spectrometry with metabolic [(2)H3]-leucine heavy isotope labeling
      under divergent conditions. We studied 7 tissues/fractions of young and old mice
      on control diet or one of 2 diet regimens (caloric restriction or rapamycin) that
      altered protein turnover (42 conditions in total). We observed a 6.5-fold
      difference in mean HL across tissues and an 11.5-fold difference across all
      conditions. Normalization to the mean HL of each condition showed that relative
      HLs were conserved across conditions (Spearman's rho = 0.57; P < 10(-4)), but
      were highly heterogeneous between subunits, with a 7.3-fold mean range overall,
      and a 2.2- to 4.6-fold range within each complex. To identify factors regulating
      this conserved distribution, we performed statistical analyses to study the
      correlation of HLs to the properties of the subunits. HLs significantly
      correlated with localization within the mitochondria, evolutionary origin,
      location of protein-encoding, and ubiquitination levels. These findings challenge
      the notion that all subunits in a complex turnover at comparable rates and
      suggest that there are common rules governing the differential proteolysis of RC
      protein subunits under divergent cellular conditions.

PMID- 25977256
TI  - Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic
      dilation.
AB  - The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic
      related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions
      are established, but those of Ang-4 are poorly understood. We used intravital
      fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma
      associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or
      VEGF-C (positive control)-expressing tumors increased to 123 and 135 MUm,
      respectively, and parental, mock-transduced (negative controls) and tumors
      expressing Ang-1 or Ang-2 remained at baseline (~60 MUm). Ang-4 decreased human
      dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while
      increasing human dermal blood endothelial cell (BEC) monolayer permeability by
      200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood
      vessel permeability compared with control when measured using intravital
      quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both
      LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor
      homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation
      detectable by immunoblotting. These data suggest that Ang-4 actions are mediated
      through cell-type-specific networks and that lymphatic vessel dilation occurs
      secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs.
      Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease
      interstitial fluid pressure (IFP) by reducing vascular permeability.

PMID- 25977258
TI  - External validation of the prognostic index in acute paraquat poisoning.
AB  - OBJECTIVE: Some studies have evaluated the prognostic indicators associated with
      acute paraquat (PQ) poisoning. In this study, we externally validated the
      Yamaguchi index, which showed a good prognostic relevance in predicting the
      outcome of PQ poisoning. METHODS: A retrospective analysis of 297 patients was
      performed. The Yamaguchi index was calculated using the following equation: Eq1 =
      (K(+) * HCO3(-))/(Creatinine * 0.088)(mEq/L) against time from PQ ingestion (T).
      The patients were divided into three groups: group A: Eq1 > 1500 - 399 * log T,
      group B: 930 - 399 * log T < Eq1 <= 1500 - 399 * log T, and group C: Eq1 <= 930 -
      399 * log T). RESULTS: The overall mortality rate was 65.3% (194 of 297). The
      mortality rates of the three groups stratified by the Yamaguchi index were 7.1%
      (2 of 28), 22.4% (15 of 67), and 87.6% (177 of 202). The area under the receiver
      operating characteristic curve for predicting mortality from the external
      validation of the Yamaguchi index was 0.842 (95% confidence interval: 0.795
      0.882). CONCLUSION: The Yamaguchi index is a reliable prognostic factor and could
      be helpful in predicting mortality due to PQ poisoning.

PMID- 25977257
TI  - Nucleophosmin contains amyloidogenic regions that are able to form toxic
      aggregates under physiological conditions.
AB  - Nucleophosmin (NPM)-1 is a multifunctional protein involved in a variety of
      biologic processes and has been implicated in the pathogenesis of several human
      malignancies. To gain insight into the role of isolated fragments in NPM1
      activities, we dissected the C-terminal domain (CTD) into its helical fragments.
      In this study, we observed the unexpected structural behavior of the peptide
      fragment corresponding to helix (H)2 (residues 264-277). This peptide has a
      strong tendency to form amyloidlike assemblies endowed with fibrillar morphology
      and beta-sheet structure, under physiologic conditions, as shown by circular
      dichroism, thioflavin T, and Congo red binding assays; dynamic light scattering;
      and atomic force microscopy. The aggregates are also toxic to neuroblastoma
      cells, as determined using 3-(4;5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide reduction and Ca(2+) influx assays. We also found that the extension of
      the H2 sequence beyond its N terminus, comprising the connecting loop with H1,
      delayed aggregation and its associated cytotoxicity, suggesting that contiguous
      regions of H2 have a protective role in preventing aggregation. Our findings and
      those in the literature suggest that the helical structures present in the CTD
      are important in preventing harmful aggregation. These findings could elucidate
      the pathogenesis of acute myeloid leukemia (AML) caused by NPM1 mutants. Because
      the CTD is not properly folded in these mutants, we hypothesize that the
      aggregation propensity of this NPM1 region is involved in the pathogenesis of
      AML. Preliminary assays on NPM1-Cter-MutA, the most frequent AML-CTD mutation,
      revealed its significant propensity for aggregation. Thus, the aggregation
      phenomena should be seriously considered in studies aimed at unveiling the
      molecular mechanisms of this pathology.

PMID- 25977259
TI  - The effects of pentoxifylline and caffeic acid phenethyl ester in the treatment
      of d-galactosamine-induced acute hepatitis in rats.
AB  - The aim of this study was to investigate histological changes in hepatic tissue
      and effects of pentoxifylline (PTX) and caffeic acid phenethyl ester (CAPE) on
      these changes using histochemical and biochemical methods in rats, in which
      hepatitis was established by D-galactosamine (D-GAL). Rats were divided into five
      groups as follows: control group, D-GAL (24 h) group, D-GAL group, d-GAL + PTX
      group, and D-GAL + CAPE group. In histological evaluations, the control group
      showed normal appearance of the liver cells. However in the d-GAL groups, focal
      areas consisting of inflammatory, necrotic, and apoptotic cells were detected in
      parenchyma. Glycogen loss was observed in the hepatocytes localized at the
      periphery of lobule. It was found that number of mast cells of portal areas were
      significantly higher in D-GAL groups compared with other groups (p = 0.0001). In
      addition, the number of cells with positive staining by Ki-67 and caspase-3 were
      significantly increased in GAL groups compared with the control group (p =
      0.0001). In biochemical analysis, there was an increase in malondialdehyde and
      myeloperoxidase levels, while a decrease was observed in glutathione level and
      glutathione peroxidase activity in groups treated with d-GAL compared with the
      control group. On the other hand, it was seen that, in the groups treated with D
      GAL, histological and biochemical injuries in the liver were reduced by
      administration of PTX and CAPE. In this study, we demonstrated the ameliorative
      effects of PTX and CAPE on D-GAL-induced liver injury.

PMID- 25977260
TI  - Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune
      Cells to and Promoting Their Activity at the Tumor.
AB  - Despite the rapid progress in the development of novel adoptive T-cell therapies,
      the clinical benefits in treatment of established tumors have remained modest.
      Several immune evasion mechanisms hinder T-cell entry into tumors and their
      activity within the tumor. Of note, oncolytic adenoviruses are intrinsically
      immunogenic due to inherent pathogen-associated molecular patterns. Here, we
      studied the capacity of adenovirus to overcome resistance of chicken ovalbumin
      expressing B16.OVA murine melanoma tumors to adoptive ovalbumin-specific CD8(+) T
      cell (OT-I) therapy. Following intraperitoneal transfer of polyclonally activated
      OT-I lymphocytes, control of tumor growth was superior in mice given intratumoral
      adenovirus compared with control mice, even in the absence of oncolytic virus
      replication. Preexisting antiviral immunity against serotype 5 did not hinder the
      therapeutic efficacy of the combination treatment. Intratumoral adenovirus
      injection was associated with an increase in proinflammatory cytokines, CD45(+)
      leukocytes, CD8(+) lymphocytes, and F4/80(+) macrophages, suggesting enhanced
      tumor immunogenicity. The proinflammatory effects of adenovirus on the tumor
      microenvironment led to expression of costimulatory signals on CD11c(+) antigen
      presenting cells and subsequent activation of T cells, thus breaking the tumor
      induced peripheral tolerance. An increased number of CD8(+) T cells specific for
      endogenous tumor antigens TRP-2 and gp100 was detected in combination-treated
      mice, indicating epitope spreading. Moreover, the majority of virus/T-cell
      treated mice rejected the challenge of parental B16.F10 tumors, suggesting that
      systemic antitumor immunity was induced. In summary, we provide proof-of
      mechanism data on combining adoptive T-cell therapy and adenovirotherapy for the
      treatment of cancer.

PMID- 25977261
TI  - Catheterization of the urethra in female pigs.
AB  - Female pigs are commonly utilized as an animal model for biomedical research and
      require urethral catheterization. Sixteen pigs were anaesthetized for research
      purposes and required the placement of a urethral catheter. Post-mortem
      examination of the vaginas revealed the urethral opening to be consistently
      halfway from the mucocutaneous junction of the vulva to the cervix. A shallow
      diverticulum was also observed on the ventral floor of the urethral opening. To
      optimize conditions for success the pig should be carefully positioned supine, a
      vaginal speculum and light source should be used, the pig should be adequately
      anaesthetized, and the anatomy of the vagina should be reviewed. 

PMID- 25977262
TI  - Proteomic analysis of nitrate-dependent acetone degradation by Alicycliphilus
      denitrificans strain BC.
AB  - Alicycliphilus denitrificans strain BC grows anaerobically on acetone with
      nitrate as electron acceptor. Comparative proteomics of cultures of A.
      denitrificans strain BC grown on either acetone or acetate with nitrate was
      performed to study the enzymes involved in the acetone degradation pathway. In
      the proposed acetone degradation pathway, an acetone carboxylase converts acetone
      to acetoacetate, an AMP-dependent synthetase/ligase converts acetoacetate to
      acetoacetyl-CoA, and an acetyl-CoA acetyltransferase cleaves acetoacetyl-CoA to
      two acetyl-CoA. We also found a putative aldehyde dehydrogenase associated with
      acetone degradation. This enzyme functioned as a beta-hydroxybutyrate
      dehydrogenase catalyzing the conversion of surplus acetoacetate to beta
      hydroxybutyrate that may be converted to the energy and carbon storage compound,
      poly-beta-hydroxybutyrate. Accordingly, we confirmed the formation of poly-beta
      hydroxybutyrate in acetone-grown cells of strain BC. Our findings provide insight
      in nitrate-dependent acetone degradation that is activated by carboxylation of
      acetone. This will aid studies of similar pathways found in other microorganisms
      degrading acetone with nitrate or sulfate as electron acceptor. 

PMID- 25977263
TI  - Toll-like Receptor 10 in Helicobacter pylori Infection.
AB  - Innate immunity plays important roles in the primary defense against pathogens,
      and epidemiological studies have suggested a role for Toll-like receptor 1 (TLR1)
      in Helicobacter pylori susceptibility. Microarray analysis of gastric biopsy
      specimens from H. pylori-positive and uninfected subjects showed that TLR10
      messenger RNA (mRNA) levels were upregulated approximately 15-fold in infected
      subjects; these findings were confirmed by real-time quantitative polymerase
      chain reaction analysis. Immunohistochemical investigation showed increased TLR10
      expression in the gastric epithelial cells of infected individuals. When H.
      pylori was cocultured with NCI-N87 gastric cells, both TLR10 and TLR2 mRNA levels
      were upregulated. We compared the ability of TLR combinations to mediate nuclear
      factor-kappaB (NF-kappaB) activation. Compared with other TLR2 subfamily
      heterodimers, the TLR2/TLR10 heterodimer mediated the greatest NF-kappaB
      activation following exposure to heat-killed H. pylori or H. pylori
      lipopolysaccharide. We conclude that TLR10 is a functional receptor involved in
      the innate immune response to H. pylori infection and that the TLR2/TLR10
      heterodimer functions in H. pylori lipopolysaccharide recognition. 

PMID- 25977264
TI  - Effect of Preexisting Serum and Mucosal Antibody on Experimental Respiratory
      Syncytial Virus (RSV) Challenge and Infection of Adults.
AB  - We studied preexisting respiratory syncytial virus (RSV)-specific serum and nasal
      antibodies and their correlation with infectivity, viral dynamics, and disease
      severity in a human experimental infection model. Higher preinoculation serum
      neutralizing antibody titers and nasal immunoglobulin (Ig) A predicted lower
      infectivity and lower measures of viral replication. However, once individuals
      were infected, no significant protective effect of preexisting antibodies was
      seen. Lack of correlation between serum and mucosal antibodies was observed,
      implying that they are independent co-correlates of protection against RSV
      infection. We suggest that protection from RSV infection is a function of a
      complex interplay between mucosal and serum humoral immune responses. 

PMID- 25977265
TI  - Red cell and platelet transfusions in neonates: a population-based study.
AB  - OBJECTIVES: This study aimed to describe the use of red cells, platelets and
      exchange transfusions among all neonates in a population cohort, to examine
      trends in transfusion over time and to determine transfusion rates in at-risk
      neonates. DESIGN: Linked population-based birth and hospital data from New South
      Wales (NSW), Australia, were used to determine rates of blood product transfusion
      in the first 28 days of life. The study included all live births >=23 weeks'
      gestation in NSW between 2001 and 2011. RESULTS: Between 2001 and 2011, 5326 of
      989 491 live born neonates received a red cell, platelet or exchange transfusion
      (5.4/1000 births). Transfusion rates were 4.8 per 1000 for red cells, 1.3 per
      1000 for platelets and 0.3 per 1000 for exchange transfusion. Overall transfusion
      rate remained constant from 2001 to 2011 (p=0.27). Among transfused neonates, 60%
      were <32 weeks' gestation (n=3210, 331/1000 births), 40% were >=32 weeks'
      gestation (n= 2116, 2/1000 births) and 7% received transfusions in a hospital
      without a neonatal intensive care unit (NICU). Factors other than prematurity
      associated with higher transfusion rates were prior in utero transfusion
      (631/1000), congenital anomaly requiring surgery (440/1000) and haemolytic
      disorder (106/1000). CONCLUSIONS: In this population-based study, preterm
      neonates had a higher rate of transfusion than term neonates; however, 40% of
      those who received a transfusion were born >=32 weeks' gestation and 7% were
      transfused in hospitals without an NICU. These findings need to be considered by
      transfusion services and personnel developing neonatal transfusion guidelines.

PMID- 25977266
TI  - High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment
      Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4
      Coinfection: The ANRS HC30 QUADRIH Study.
AB  - BACKGROUND: Few direct anti-hepatitis C virus (HCV) agents have been studied in
      difficult-to-treat null responder and cirrhotic human immunodeficiency virus
      (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated
      interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV
      monoinfected patients. METHODS: An open-label, single-arm, phase 2 study was
      conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to
      prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV
      RNA <400 copies/mL. They received a 4-week lead-in phase with peg-IFN/RBV,
      followed by 24 weeks of asunaprevir (100 mg twice daily), daclatasvir (60 mg once
      daily), and peg-IFN/RBV. The primary endpoint was sustained virologic response 12
      weeks after the end of treatment (SVR12) using intent-to-treat analysis. RESULTS:
      Seventy-five patients were included, of whom 27 (36%) had cirrhosis. The median
      baseline CD4 count was 748 (interquartile range, 481-930) cells/uL. The global
      SVR12 rate was 96.0% (95% confidence interval [CI], 88.8%-99.2%; n = 72/75),
      92.6% (95% CI, 75.7%-99.1%; n = 25/27) in cirrhotic patients, 94.6% (95% CI,
      81.8%-99.3%; n = 35/37) in genotype 1 patients, and 97.4% (95% CI, 86.2%-99.9%; n
      = 37/38) in genotype 4 patients. Six patients (8%) stopped HCV therapy
      prematurely: 2 due to HCV breakthrough, 4 to adverse events (1 lung cancer, 3
      infections). One patient with cirrhosis (with baseline platelet count <150 000
      platelets/uL and albuminemia <35 g/L) died from multiorgan failure. Overall, 36
      serious adverse events occurred in 21 (28%) patients. No HIV breakthrough was
      observed. CONCLUSIONS: In HIV/HCV genotype 1/4-coinfected null responders, a 24
      week regimen combining daclatasvir, asunaprevir, and peg-IFN/RBV was associated
      with a very high cure rate. The safety profile was acceptable, even though
      cirrhotic patients with low albuminemia and platelets should be monitored
      closely. This combination is a new option in this difficult-to-treat population.
      CLINICAL TRIALS REGISTRATION: NCT01725542.

PMID- 25977267
TI  - Editorial Commentary: Who is "Special" Now?

PMID- 25977268
TI  - PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.
AB  - Donor PTX3 polymorphisms were shown to influence the risk of invasive
      aspergillosis among hematopoietic stem cell transplant recipients. Here, we show
      that PTX3 polymorphisms are independent risk factors for invasive mold infections
      among 1101 solid organ transplant recipients, thereby strengthening their role in
      mold infection pathogenesis and patients' risk stratification. 

PMID- 25977271
TI  - Myasthenia gravis: Association of British Neurologists' management guidelines.
AB  - Myasthenia gravis is an autoimmune disease of the neuromuscular junction for
      which many therapies were developed before the era of evidence based medicine.
      The basic principles of treatment are well known, however, patients continue to
      receive suboptimal treatment as a result of which a myasthenia gravis guidelines
      group was established under the aegis of The Association of British Neurologists.
      These guidelines attempt to steer a path between evidence-based practice where
      available, and established best practice where evidence is unavailable. Where
      there is insufficient evidence or a choice of options, the guidelines invite the
      clinician to seek the opinion of a myasthenia expert. The guidelines support
      clinicians not just in using the right treatments in the right order, but in
      optimising the use of well-known therapeutic agents. Clinical practice can be
      audited against these guidelines. 

PMID- 25977272
TI  - Whippits, nitrous oxide and the dangers of legal highs.
AB  - Nitrous oxide is increasingly being used as a recreational drug. Prolonged use of
      nitrous oxide can have disabling neurological sequelae due to functional
      inactivation of vitamin B12. We present three cases illustrating the neurological
      complications of using nitrous oxide. Two of these patients received nitrous
      oxide as a consequence of repeated hospital attendance and the third via
      'Whippit' canisters used in cream dispensers, which are now widely available. Two
      patients developed sensorimotor peripheral neuropathy with demyelinating features
      with no clinical or imaging evidence of myelopathy, emphasising that not all
      patients develop subacute combined degeneration of the spinal cord (the typical
      presentation of functional vitamin B12 deficiency). The diagnosis was based upon
      the history of nitrous oxide use and raised levels of homocysteine and/or
      methylmalonic acid. All patients were treated with parenteral vitamin B12 with
      partial recovery, though two were left significantly disabled.

PMID- 25977274
TI  - Letter by Kawada Regarding Article, "Carotid Intima-Media Thickness Is Associated
      With the Progression of Cognitive Impairment in Older Adults".

PMID- 25977270
TI  - Concussion is confusing us all.
AB  - It is time to stop using the term concussion as it has no clear definition and no
      pathological meaning. This confusion is increasingly problematic as the
      management of 'concussed' individuals is a pressing concern. Historically, it has
      been used to describe patients briefly disabled following a head injury, with the
      assumption that this was due to a transient disorder of brain function without
      long-term sequelae. However, the symptoms of concussion are highly variable in
      duration, and can persist for many years with no reliable early predictors of
      outcome. Using vague terminology for post-traumatic problems leads to
      misconceptions and biases in the diagnostic process, producing uninterpretable
      science, poor clinical guidelines and confused policy. We propose that the term
      concussion should be avoided. Instead neurologists and other healthcare
      professionals should classify the severity of traumatic brain injury and then
      attempt to precisely diagnose the underlying cause of post-traumatic symptoms. 

PMID- 25977275
TI  - Dimethyl Fumarate Protects Brain From Damage Produced by Intracerebral Hemorrhage
      by Mechanism Involving Nrf2.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) represents a devastating
      form of stroke for which there is no effective treatment. This preclinical study
      was designed to evaluate dimethyl fumarate (DMF), a substance recently approved
      for the treatment of multiple sclerosis, as therapy for ICH. We hypothesized that
      DMF through activating the master regulator of cellular self-defense responses,
      transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), would
      act as effective treatment for ICH-mediated damage. METHODS: Male rats and mice,
      including Nrf2 knockouts, were subjected to intracerebral injection of blood (to
      mimic ICH) and then treated with DMF. Neurological deficit, brain edema, gene
      induction profile and hematoma resolution were evaluated. Phagocytic functions of
      primary microglia in culture were used to study hematoma resolution. RESULTS:
      Treatment with DMF induced Nrf2-target genes, improved hematoma resolution,
      reduced brain edema, and ultimately enhanced neurological recovery in rats and
      wild-type, but not Nrf2 knockout, mice. Most importantly, the treatment of ICH
      with DMF showed a 24 h window of therapeutic opportunity. CONCLUSIONS: A
      clinically relevant dose of DMF demonstrates potent therapeutic efficacy and
      impressive 24 h therapeutic window of opportunity. This study merits further
      evaluation of this compound as potential treatment for ICH in humans.

PMID- 25977277
TI  - Response to Letter Regarding Article, "Carotid Intima-Media Thickness Is
      Associated With the Progression of Cognitive Impairment in Older Adults".

PMID- 25977276
TI  - The VASOGRADE: A Simple Grading Scale for Prediction of Delayed Cerebral Ischemia
      After Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Patients are classically at risk of delayed cerebral
      ischemia (DCI) after aneurysmal subarachnoid hemorrhage. We validated a grading
      scale-the VASOGRADE-for prediction of DCI. METHODS: We used data of 3 phase II
      randomized clinical trials and a single hospital series to assess the
      relationship between the VASOGRADE and DCI. The VASOGRADE derived from previously
      published risk charts and consists of 3 categories: VASOGRADE-Green (modified
      Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale [WFNS]
      1 or 2); VASOGRADE-Yellow (modified Fisher 3 or 4 and WFNS 1-3); and VASOGRADE
      Red (WFNS 4 or 5, irrespective of modified Fisher grade). The relation between
      the VASOGRADE and DCI was assessed by logistic regression models. The predictive
      accuracy of the VASOGRADE was assessed by receiver operating characteristics
      curve and calibration plots. RESULTS: In a cohort of 746 patients, the VASOGRADE
      significantly predicted DCI (P<0.001). The VASOGRADE-Yellow had a tendency for
      increased risk for DCI (odds ratio [OR], 1.31; 95% CI, 0.77-2.23) when compared
      with VASOGRADE-Green; those with VASOGRADE-Red had a 3-fold higher risk of DCI
      (OR, 3.19; 95% CI, 2.07-4.50). Studies were not a significant confounding factor
      between the VASOGRADE and DCI. The VASOGRADE had an adequate discrimination for
      prediction of DCI (area under the receiver operating characteristics curve=0.63)
      and good calibration. CONCLUSIONS: The VASOGRADE results validated previously
      published risk charts in a large and diverse sample of subarachnoid hemorrhage
      patients, which allows DCI risk stratification on presentation after subarachnoid
      hemorrhage. It could help to select patients at high risk of DCI, as well as
      standardize treatment protocols and research studies.

PMID- 25977278
TI  - Visualizing Acute Stroke Data to Improve Clinical Outcomes.

PMID- 25977280
TI  - Arcobacter lanthieri sp. nov., isolated from pig and dairy cattle manure.
AB  - A study was undertaken to determine the prevalence and diversity of species of
      the genus Arcobacter in pig and dairy cattle manure, which led to the
      identification of strains AF1440T, AF1430 and AF1581. Initially identified as
      Arcobacter butzleri based on colony morphology and initial PCR-confirmation
      tests, analyses of 16S rRNA gene sequences of these strains confirmed that they
      belonged to the genus Arcobacter and were different from all known species of the
      genus. The isolates formed a distinct group within the genus Arcobacter based on
      their 16S rRNA, gyrB, rpoB, cpn60, gyrA and atpA gene sequences and fatty acid
      profiles. Their unique species status was further supported by physiological
      properties and DNA-DNA hybridization that allowed phenotypic and genotypic
      differentiation of the strains from other species of the genus Arcobacter. The
      isolates were found to be oxidase, catalase and esterase positive and urease
      negative; they grew well at 30  degrees C under microaerophilic conditions and
      produced nitrite and acetoin. Based on their common origin and various
      physiological properties, it is proposed that the isolates are classified as
      members of a novel species with the name Arcobacter lanthieri sp. nov. The type
      strain is AF1440T ( = LMG 28516T = CCUG 66485T); strains AF1430 ( = LMG 28515 =
      CCUG 66486) and AF1581 ( = LMG 28517 = CCUG 66487) are reference strains. 

PMID- 25977281
TI  - Paenibacillus oenotherae sp. nov. and Paenibacillus hemerocallicola sp. nov.,
      isolated from the roots of herbaceous plants.
AB  - Two Gram-staining-positive, aerobic, endospore-forming, motile bacteria, strains
      DT7-4T and DLE-12T, were isolated from roots of evening primrose (Oenothera
      biennis) and day lily (Hemerocallis fulva), respectively, and subjected to
      taxonomic characterization. Analysis of 16S rRNA gene sequences indicated that
      the two strains fell into two distinct phylogenetic clusters belonging to the
      genus Paenibacillus. Strain DT7-4T was most closely related to Paenibacillus
      phyllosphaerae PALXIL04T and Paenibacillus taihuensis THMBG22T, with 96.3% 16S
      rRNA gene sequence similarity to each, and strain DLE-12T was most closely
      related to Paenibacillus ginsengarvi Gsoil 139T and Paenibacillus hodogayensis
      SGT, with 96.6 and 93.3% sequence similarity, respectively. Both isolates
      contained anteiso-C15 : 0 as the dominant fatty acid, meso-diaminopimelic acid as
      the diagnostic diamino acid in the cell-wall peptidoglycan and MK-7 as the
      respiratory menaquinone. The cellular polar lipids were composed of
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and
      unidentified polar lipids. The DNA G+C contents of strains DT7-4T and DLE-12T
      were 50.1 +/- 0.7 and 55.2 +/- 0.5 mol%, respectively. The chemotaxonomic
      properties of both isolates were typical of members of the genus Paenibacillus.
      However, our biochemical and phylogenetic analyses distinguished each isolate
      from related species. Based on our polyphasic taxonomic analysis, strains DT7-4T
      and DLE-12T should be recognized as representatives of novel species of
      Paenibacillus, for which the names Paenibacillus oenotherae sp. nov. (type strain
      DT7-4T = KCTC 33186T = JCM 19573T) and Paenibacillus hemerocallicola sp. nov.
      (type strain DLE-12T = KCTC 33185T = JCM 19572T) are proposed.

PMID- 25977282
TI  - Risungbinella pyongyangensis gen. nov., sp. nov., a mesophilic member of the
      family Thermoactinomycetaceae isolated from an agricultural soil sample.
AB  - A mesophilic strain, designed MC 210T, was isolated from an agricultural soil
      sample from Pyongyang, Democratic People's Republic of Korea, and its taxonomic
      position was investigated by using a polyphasic approach. The novel strain grew
      well on PYI medium, and no diffusible pigments were produced. The optimum
      temperature for growth was 37  degrees C. The aerial mycelium was well developed,
      but not fragmented. The strain was Gram-reaction-positive and non-motile and
      formed endospores on the aerial mycelium. Phylogenetic analysis based on the 16S
      rRNA gene sequence indicated that strain MC 210T belongs to the family
      Thermoactinomycetaceae. Strain MC 210T showed 16S rRNA gene sequence similarities
      of 92.90 and 92.54% to the type strains of Geothermomicrobium terrae and
      Shimazuella kribbensis, respectively. The cell wall of strain MC 210T contained
      meso-diaminopimelic acid, glutamic acid and alanine as the diagnostic amino
      acids, and whole-cell hydrolysates contained glucose, arabinose and galactose.
      Strain MC 210T contained anteiso-C13 : 0, iso-C14 : 0, C14 : 0, anteiso-C15 : 0,
      C16 : 0 and iso-C13 : 0 as the major cellular fatty acids. The main polar lipids
      were phosphatidylethanolamine, phosphatidylmethylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, two unknown aminophospholipids, an
      unknown aminolipid, three unknown phospholipids and five unknown polar lipids.
      The predominant menaquinone was MK-7.The G+C content of the genomic DNA was 42.1
      mol%. On the basis of our phylogenetic, physiological and chemotaxonomic data,
      strain MC 210T is considered to represent a novel genus and species, for which we
      propose the name Risungbinella pyongyangensis gen. nov., sp. nov., in the family
      Thermoactinomycetaceae. The type strain of Risungbinella pyongyangensis is MC
      210T (CCTCC AA 2013021T = NRRL B-59118T).

PMID- 25977283
TI  - Humibacter ginsengiterrae sp. nov., and Humibacter ginsengisoli sp. nov.,
      isolated from soil of a ginseng field.
AB  - Two novel Gram-staining-positive bacteria, designated DCY60T and DCY90T, were
      isolated from soil of a ginseng field in the Republic of Korea. 16S rRNA gene
      sequence comparisons showed the two novel strains were closely related to members
      of the genus Humibacter with greatest similarity to Humibacter antri KCTC 33009T
      (98.8 and 98.4% for DCY60T and DCY90T, respectively). The predominant
      menaquinones present were MK-11 and MK-12. The major fatty acids were anteiso-C17
      : 0 and summed feature 8 containing C18 : 1omega7c and/or C18 : 1omega6c. The DNA
      G+C contents of strains DCY60T and DCY90T were 62.8 and 66.8 mol%, respectively.
      The peptidoglycan of both strains contained the amino acids ornithine, 2,4
      diaminobutyric acid, alanine, glutamic acid and glycine. The cell-wall sugars of
      strain DCY60T comprised glucose, galactose, rhamnose and xylose, while strain
      DCY90T contained glucose, galactose, rhamnose and ribose. The major polar lipids
      of both strains were phosphatidylglycerol, an unidentified glycolipid, and an
      unknown phospholipid. On the basis of the phenotypic analysis strains DCY60T and
      DCY90T represent novel species of the genus Humibacter, for which names
      Humibacter ginsengiterrae sp. nov. (type strain DCY60T = KCTC 33520T = JCM
      30079T) and Humibacter ginsengisoli sp. nov. (type strain DCY90T = KCTC 33521T =
      JCM 30080T) are proposed.

PMID- 25977279
TI  - Hemodynamic Features of Symptomatic Vertebrobasilar Disease.
AB  - BACKGROUND AND PURPOSE: Atherosclerotic vertebrobasilar disease is an important
      cause of posterior circulation stroke. To examine the role of hemodynamic
      compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and
      Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we
      report clinical features and vessel flow measurements from the study cohort.
      METHODS: Patients with recent vertebrobasilar transient ischemic attack or stroke
      and >=50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries
      (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was
      assessed using quantitative MRA. RESULTS: The cohort (n=72; 44% women) had a mean
      age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and
      hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows
      correlated negatively with percentage stenosis in the affected vessel and
      positively to the minimal diameter at the stenosis site (P<0.01). A relative
      threshold effect was evident, with flows dropping most significantly with >=80%
      stenosis/occlusion (P<0.05). Tandem disease involving the BA and either/both
      vertebral arteries had the greatest negative impact on immediate downstream flow
      in the BA (43 mL/min versus 71 mL/min; P=0.01). Distal flow status assessment,
      based on an algorithm incorporating collateral flow by examining distal vessels
      (BA and posterior cerebral arteries), correlated neither with multifocality of
      disease nor with severity of the maximal stenosis. CONCLUSIONS: Flow in stenotic
      posterior circulation vessels correlates with residual diameter and drops
      significantly with tandem disease. However, distal flow status, incorporating
      collateral capacity, is not well predicted by the severity or location of the
      disease.

PMID- 25977284
TI  - Shimia sagamensis sp. nov., a marine bacterium isolated from cold-seep sediment.
AB  - A novel marine bacterial strain designated JAMH 011(T) was isolated from the cold
      seep sediment in Sagami Bay, Japan. Cells were Gram-stain-negative, rod-shaped,
      non-spore-forming, aerobic chemo-organotrophs and motile by means of a single
      polar flagellum. Growth occurred at temperatures below 31  degrees C, with the
      optimum at 25  degrees C. The major respiratory quinone was Q-10. The predominant
      fatty acid was C18 : 1omega7c. On the basis of 16S rRNA gene sequence analysis,
      the isolated strain was closely affiliated with members of the genus Shimia in
      the class Alphaproteobacteria, and the 16S rRNA gene sequence similarity of the
      novel isolate with the type strain of the closest related species, Shimia
      haliotis WM35(T), was 98.1%. The DNA G+C content of the novel strain was 57.3
      mol%. The hybridization values for DNA-DNA relatedness between strain JAMH 011(T)
      and reference strains belonging to the genus Shimia were less than 9.4 +/- 0.7%.
      Based on differences in taxonomic characteristics, the isolated strain represents
      a novel species of the genus Shimia, for which the name Shimia sagamensis sp.
      nov. is proposed. The type strain is JAMH 011(T) ( = JCM 30583(T) = DSM
      29734(T)).

PMID- 25977285
TI  - Reclassification of Bacillus invictae as a later heterotypic synonym of Bacillus
      altitudinis.
AB  - The aim of this study was to reclarify the taxonomic status of strain Bacillus
      invictae Bi.FFUP1T by performing comparative analyses with the other four type
      strains within the Bacillus pumilus group. The digital DNA-DNA hybridization
      (dDDH) and average nucleotide identity (ANI) values between strains B. invictae
      Bi.FFUP1T ( = DSMZ 26896T = MCCC 1A07089T), B. altitudinis 41KF2bT ( = DSMZ
      21631T = MCCC 1A06452T), B. safensis FO-36bT ( = DSMZ 19292T = MCCC 1A6451T), B.
      pumilus ATCC 7061T ( = DSMZ 27T = MCCC 1A06453T) and B. xiamenensis HYC-10T ( =
      MCCC 1A00008T) were, respectively, 82.90  % and 98.10  %, which are greater than
      the thresholds for bacterial species delineation, suggesting that they should
      belong to the same species, while the dDDH and ANI values between strain B.
      invictae DSMZ 26896T and the other three type strains within the B. pumilus group
      were below the respective thresholds of 70  % and 95  %. Meanwhile, B. invictae
      DSMZ 26896T and B. altitudinis 41KF2bT shared 98.7  % gyrB gene sequence
      similarity based on resequencing, whereas strain B. invictae DSMZ 26896T shared
      low similarities ( < 95  %) with the other three type strains. In addition, in
      comparison with those from the other three type strains, phenotypic data of B.
      invictae DSMZ 26896T and B. altitudinis 41KF2bT, including API 20NE, API ZYM,
      Biolog GN2 and API 50CHB tests, showed slight differences. The data from these
      combined genotypic and phenotypic analyses suggest that Bacillus invictae
      Branquinho et al. 2014 should be regarded as a later heterotypic synonym of
      Bacillus altitudinisShivaji et al. 2006. 

PMID- 25977286
TI  - Teleost leukocyte immune-type receptors activate distinct phagocytic modes for
      target acquisition and engulfment.
AB  - Channel catfish (Ictalurus punctatus) IpLITRs belong to the Ig superfamily and
      regulate innate immune cell effector responses. This study tested the hypothesis
      that ITAM-dependent and ITAM-independent phagocytic pathways are engaged by
      different subtypes of the IpLITR family. When stably expressed in RBL-2H3 cells,
      the ITAM-containing fusion-construct IpLITR 2.6b/IpFcRgamma-L stimulated
      phagocytic responses that were abrogated at suboptimal incubation temperatures
      and by pharmacological inhibitors of the classic signaling components of the
      mammalian FcR-dependent phagocytic pathway. Interestingly, the ITIM-containing
      receptor IpLITR 1.1b also induced phagocytosis through an actin-dependent
      mechanism, but this process was insensitive to the pharmacological inhibitors
      tested and remained functional at temperatures as low as 22 degrees C. The IpLITR
      1.1b also displayed a unique target-acquisition phenotype that consisted of
      complex, membranous protrusions, which captured targets in phagocytic cup-like
      structures but often failed to completely engulf targets. Taken together, these
      findings suggest that teleost immunoregulatory receptors that associate with ITAM
      containing adaptors can engage conserved components of the phagocytic machinery
      to engulf extracellular targets akin to the classic FcR-mediated response in
      mammals. Alternatively, IpLITR 1.1b displays a stalled phagocytic phenotype that
      is likely dependent on the selective recruitment of the minimal molecular
      machinery required for target capture but results in incomplete target
      engulfment. Overall, this study demonstrates that IpLITRs can selectively engage
      distinct components of the phagocytic process and provides important new
      information regarding the target acquisition as well as internalization
      mechanisms involved in controlling phagocytic responses across vertebrates. 

PMID- 25977287
TI  - The role of EMMPRIN in T cell biology and immunological diseases.
AB  - EMMPRIN (CD147), originally described as an inducer of the expression of MMPs,
      has gained attention in its involvement in various immunologic diseases, such
      that anti-EMMPRIN antibodies are considered as potential therapeutic medications.
      Given that MMPs are involved in the pathogenesis of various disease states, it is
      relevant that targeting an upstream inducer would make for an effective
      therapeutic strategy. Additionally, EMMPRIN is now appreciated to have multiple
      roles apart from MMP induction, including in cellular functions, such as
      migration, adhesion, invasion, energy metabolism, as well as T cell activation
      and proliferation. Here, we review what is known about EMMPRIN in numerous
      immunologic/inflammatory disease conditions with a particular focus on its
      complex roles in T cell biology. 

PMID- 25977288
TI  - Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target
      the disease-relevant neutrophil phenotype?
AB  - In severe, neutrophilic asthma, neutrophils are thought to have an important role
      in both the maintenance of the disease and during exacerbations. These patients
      often display excessive, mucosal airway inflammation with unresolving
      neutrophilia. Because this variant of asthma is poorly controlled by
      glucocorticoids, specific pharmacologic targeting of neutrophils seems a
      plausible therapeutic approach. However, most attempts with this approach have
      failed in the clinic. We propose that this could be attributed, in part, to an
      incomplete understanding of the emerging new insights underlying neutrophil
      homeostasis and life span, neutrophil reverse transmigration, neutrophil
      phenotypes, and neutrophil transdifferentiation in human health and disease. Of
      clinical relevance, recent translational studies have started to uncover distinct
      neutrophil subsets in humans, namely mature and hypersegmented phenotypes that
      have bimodal immunomodulatory functions during an acute inflammatory response. In
      this review, we will elaborate on some of the novel insights in neutrophil
      biology and attempt to translate them into potential consequences for
      pharmacologic intervention of severe neutrophilic asthma. We speculate that the
      disease-relevant neutrophil phenotype should be targeted selectively without
      compromising the immunomodulatory functions essential for homeostasis and
      pulmonary immunity. However, the identity and exact functional role of distinct
      neutrophil phenotypes in inflammatory diseases of the human airway remain
      elusive. 

PMID- 25977289
TI  - An increased expression of PI-PLCbeta1 is associated with myeloid differentiation
      and a longer response to azacitidine in myelodysplastic syndromes.
AB  - This study tested the hypothesis that PI-PLCbeta1 is associated with myeloid
      differentiation and that its expression could be useful for predicting the
      response of MDS patients to azacitidine, as the clinical effect of epigenetic
      treatments is often detectable only after several cycles of therapy. To this end,
      PI-PLCbeta1 was quantified on 70 MDS patients (IPSS risk: 13 Low, 20 Int-1, 31
      Int-2, 6 High) at baseline and during the first 3 cycles of azacitidine. Results
      were then compared with the hematologic response, as assessed after the sixth
      cycle of azacitidine therapy. Overall, 60 patients completed 6 cycles of
      azacitidine, and for them, a clinical and molecular evaluation was possible: 37
      of these patients (62%) showed a specific increase of PI-PLCbeta1 mRNA within the
      first 3 cycles, which was associated with a longer duration of response and with
      an increased myeloid differentiation, as evidenced by PI-PLCgamma2 induction and
      the recruitment of specific myeloid-associated transcription factors to the PI
      PLCbeta1 promoter during azacitidine response. Moreover, the increase of cyclin
      D3 gene expression throughout all of the therapy showed that PI-PLCbeta1
      dependent signaling is indeed activated in azacitidine responder patients. Taken
      together, our results show that PI-PLCbeta1 quantification in MDS predicts the
      response to azacitidine and is associated with an increased myeloid
      differentiation. 

PMID- 25977290
TI  - British Thoracic Society community acquired pneumonia guideline and the NICE
      pneumonia guideline: how they fit together.
AB  - The British Thoracic Society (BTS) guideline for the management of adults with
      community acquired pneumonia (CAP) published in 2009 was compared with the 2014
      National Institute for Health and Care Excellence (NICE) Pneumonia Guideline. Of
      the 36 BTS recommendations that overlapped with NICE recommendations, no major
      differences were found in 31, including those covering key aspects of CAP
      management: timeliness of diagnosis and treatment, severity assessment and
      empirical antibiotic choice. Of the five BTS recommendations where major
      differences with NICE were identified, one related to antibiotic duration in low
      and moderate severity CAP, two to the timing of review of patients and two to
      legionella urinary antigen testing. 

PMID- 25977292
TI  - BCSearch: fast structural fragment mining over large collections of protein
      structures.
AB  - Resources to mine the large amount of protein structures available today are
      necessary to better understand how amino acid variations are compatible with
      conformation preservation, to assist protein design, engineering and, further,
      the development of biologic therapeutic compounds. BCSearch is a versatile
      service to efficiently mine large collections of protein structures. It relies on
      a new approach based on a Binet-Cauchy kernel that is more discriminative than
      the widely used root mean square deviation criterion. It has statistics
      independent of size even for short fragments, and is fast. The systematic mining
      of large collections of structures such as the complete SCOPe protein structural
      classification or comprehensive subsets of the Protein Data Bank can be performed
      in few minutes. Based on this new score, we propose four innovative applications:
      BCFragSearch and BCMirrorSearch, respectively, search for fragments similar and
      anti-similar to a query and return information on the diversity of the sequences
      of the hits. BCLoopSearch identifies candidate fragments of fixed size matching
      the flanks of a gaped structure. BCSpecificitySearch analyzes a complete protein
      structure and returns information about sites having few similar fragments.
      BCSearch is available at http://bioserv.rpbs.univ-paris
      diderot.fr/services/BCSearch. 

PMID- 25977291
TI  - Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and
      cancer progression.
AB  - The ectonucleotide pyrophosphatase/phosphodiesterase type 2, more commonly known
      as autotaxin (ATX), is an ecto-lysophospholipase D encoded by the human ENNP2
      gene. ATX is expressed in multiple tissues and participates in numerous key
      physiologic and pathologic processes, including neural development, obesity,
      inflammation, and oncogenesis, through the generation of the bioactive lipid,
      lysophosphatidic acid. Overwhelming evidence indicates that altered ATX activity
      leads to oncogenesis and cancer progression through the modulation of multiple
      hallmarks of cancer pathobiology. Here, we review the structural and catalytic
      characteristics of the ectoenzyme, how its expression and maturation processes
      are regulated, and how the systemic integration of its pleomorphic effects on
      cells and tissues may contribute to cancer initiation, progression, and therapy.
      Additionally, the up-to-date spectrum of the most frequent ATX genomic
      alterations from The Cancer Genome Atlas project is reported for a subset of
      cancers. 

PMID- 25977293
TI  - Web-Beagle: a web server for the alignment of RNA secondary structures.
AB  - Web-Beagle (http://beagle.bio.uniroma2.it) is a web server for the pairwise
      global or local alignment of RNA secondary structures. The server exploits a new
      encoding for RNA secondary structure and a substitution matrix of RNA structural
      elements to perform RNA structural alignments. The web server allows the user to
      compute up to 10 000 alignments in a single run, taking as input sets of RNA
      sequences and structures or primary sequences alone. In the latter case, the
      server computes the secondary structure prediction for the RNAs on-the-fly using
      RNAfold (free energy minimization). The user can also compare a set of input RNAs
      to one of five pre-compiled RNA datasets including lncRNAs and 3' UTRs. All types
      of comparison produce in output the pairwise alignments along with structural
      similarity and statistical significance measures for each resulting alignment. A
      graphical color-coded representation of the alignments allows the user to easily
      identify structural similarities between RNAs. Web-Beagle can be used for finding
      structurally related regions in two or more RNAs, for the identification of
      homologous regions or for functional annotation. Benchmark tests show that Web
      Beagle has lower computational complexity, running time and better performances
      than other available methods. 

PMID- 25977294
TI  - DIANA-miRPath v3.0: deciphering microRNA function with experimental support.
AB  - The functional characterization of miRNAs is still an open challenge. Here, we
      present DIANA-miRPath v3.0 (http://www.microrna.gr/miRPathv3) an online software
      suite dedicated to the assessment of miRNA regulatory roles and the
      identification of controlled pathways. The new miRPath web server renders
      possible the functional annotation of one or more miRNAs using standard
      (hypergeometric distributions), unbiased empirical distributions and/or meta
      analysis statistics. DIANA-miRPath v3.0 database and functionality have been
      significantly extended to support all analyses for KEGG molecular pathways, as
      well as multiple slices of Gene Ontology (GO) in seven species (Homo sapiens, Mus
      musculus, Rattus norvegicus, Drosophila melanogaster, Caenorhabditis elegans,
      Gallus gallus and Danio rerio). Importantly, more than 600 000 experimentally
      supported miRNA targets from DIANA-TarBase v7.0 have been incorporated into the
      new schema. Users of DIANA-miRPath v3.0 can harness this wealth of information
      and substitute or combine the available in silico predicted targets from DIANA
      microT-CDS and/or TargetScan v6.2 with high quality experimentally supported
      interactions. A unique feature of DIANA-miRPath v3.0 is its redesigned Reverse
      Search module, which enables users to identify and visualize miRNAs significantly
      controlling selected pathways or belonging to specific GO categories based on in
      silico or experimental data. DIANA-miRPath v3.0 is freely available to all users
      without any login requirement. 

PMID- 25977296
TI  - NPDock: a web server for protein-nucleic acid docking.
AB  - Protein-RNA and protein-DNA interactions play fundamental roles in many
      biological processes. A detailed understanding of these interactions requires
      knowledge about protein-nucleic acid complex structures. Because the experimental
      determination of these complexes is time-consuming and perhaps futile in some
      instances, we have focused on computational docking methods starting from the
      separate structures. Docking methods are widely employed to study protein-protein
      interactions; however, only a few methods have been made available to model
      protein-nucleic acid complexes. Here, we describe NPDock (Nucleic acid-Protein
      Docking); a novel web server for predicting complexes of protein-nucleic acid
      structures which implements a computational workflow that includes docking,
      scoring of poses, clustering of the best-scored models and refinement of the most
      promising solutions. The NPDock server provides a user-friendly interface and 3D
      visualization of the results. The smallest set of input data consists of a
      protein structure and a DNA or RNA structure in PDB format. Advanced options are
      available to control specific details of the docking process and obtain
      intermediate results. The web server is available at http://genesilico.pl/NPDock.

PMID- 25977295
TI  - Longitudinal epigenetic and gene expression profiles analyzed by three-component
      analysis reveal down-regulation of genes involved in protein translation in human
      aging.
AB  - Data on biological mechanisms of aging are mostly obtained from cross-sectional
      study designs. An inherent disadvantage of this design is that inter-individual
      differences can mask small but biologically significant age-dependent changes. A
      serially sampled design (same individual at different time points) would overcome
      this problem but is often limited by the relatively small numbers of available
      paired samples and the statistics being used. To overcome these limitations, we
      have developed a new vector-based approach, termed three-component analysis,
      which incorporates temporal distance, signal intensity and variance into one
      single score for gene ranking and is combined with gene set enrichment analysis.
      We tested our method on a unique age-based sample set of human skin fibroblasts
      and combined genome-wide transcription, DNA methylation and histone methylation
      (H3K4me3 and H3K27me3) data. Importantly, our method can now for the first time
      demonstrate a clear age-dependent decrease in expression of genes coding for
      proteins involved in translation and ribosome function. Using analogies with data
      from lower organisms, we propose a model where age-dependent down-regulation of
      protein translation-related components contributes to extend human lifespan.

PMID- 25977297
TI  - PrionW: a server to identify proteins containing glutamine/asparagine rich prion
      like domains and their amyloid cores.
AB  - Prions are a particular type of amyloids with the ability to self-perpetuate and
      propagate in vivo. Prion-like conversion underlies important biological processes
      but is also connected to human disease. Yeast prions are the best understood
      transmissible amyloids. In these proteins, prion formation from an initially
      soluble state involves a structural conversion, driven, in many cases, by
      specific domains enriched in glutamine/asparagine (Q/N) residues. Importantly,
      domains sharing this compositional bias are also present in the proteomes of
      higher organisms, thus suggesting that prion-like conversion might be an
      evolutionary conserved mechanism. We have recently shown that the identification
      and evaluation of the potency of amyloid nucleating sequences in putative prion
      domains allows discrimination of genuine prions. PrionW is a web application that
      exploits this principle to scan sequences in order to identify proteins
      containing Q/N enriched prion-like domains (PrLDs) in large datasets. When used
      to scan the complete yeast proteome, PrionW identifies previously experimentally
      validated prions with high accuracy. Users can analyze up to 10 000 sequences at
      a time, PrLD-containing proteins are identified and their putative PrLDs and
      amyloid nucleating cores visualized and scored. The output files can be
      downloaded for further analysis. PrionW server can be accessed at
      http://bioinf.uab.cat/prionw/. 

PMID- 25977299
TI  - ZCURVE 3.0: identify prokaryotic genes with higher accuracy as well as
      automatically and accurately select essential genes.
AB  - In 2003, we developed an ab initio program, ZCURVE 1.0, to find genes in
      bacterial and archaeal genomes. In this work, we present the updated version
      (i.e. ZCURVE 3.0). Using 422 prokaryotic genomes, the average accuracy was 93.7%
      with the updated version, compared with 88.7% with the original version. Such
      results also demonstrate that ZCURVE 3.0 is comparable with Glimmer 3.02 and may
      provide complementary predictions to it. In fact, the joint application of the
      two programs generated better results by correctly finding more annotated genes
      while also containing fewer false-positive predictions. As the exclusive
      function, ZCURVE 3.0 contains one post-processing program that can identify
      essential genes with high accuracy (generally >90%). We hope ZCURVE 3.0 will
      receive wide use with the web-based running mode. The updated ZCURVE can be
      freely accessed from http://cefg.uestc.edu.cn/zcurve/ or
      http://tubic.tju.edu.cn/zcurveb/ without any restrictions. 

PMID- 25977298
TI  - Heterologous protein production using euchromatin-containing expression vectors
      in mammalian cells.
AB  - Upon stable cell line generation, chromosomal integration site of the vector DNA
      has a major impact on transgene expression. Here we apply an active gene
      environment, rather than specified genetic elements, in expression vectors used
      for random integration. We generated a set of Bacterial Artificial Chromosome
      (BAC) vectors with different open chromatin regions, promoters and gene
      regulatory elements and tested their impact on recombinant protein expression in
      CHO cells. We identified the Rosa26 BAC as the most efficient vector backbone
      showing a nine-fold increase in both polyclonal and clonal production of the
      human IgG-Fc. Clonal protein production was directly proportional to integrated
      vector copy numbers and remained stable during 10 weeks without selection
      pressure. Finally, we demonstrated the advantages of BAC-based vectors by
      producing two additional proteins, HIV-1 glycoprotein CN54gp140 and HIV-1
      neutralizing PG9 antibody, in bioreactors and shake flasks reaching a production
      yield of 1 g/l. 

PMID- 25977300
TI  - Editor's note.

PMID- 25977301
TI  - Does ischemia burden in stable coronary artery disease effectively identify
      revascularization candidates? Ischemia burden in stable coronary artery disease
      effectively identifies revascularization candidates.

PMID- 25977302
TI  - Does ischemia burden in stable coronary artery disease effectively identify
      revascularization candidates? Ischemia burden in stable coronary artery disease
      does not effectively identify revascularization candidates.

PMID- 25977303
TI  - Leaflet area as a determinant of tricuspid regurgitation severity in patients
      with pulmonary hypertension.
AB  - BACKGROUND: Tricuspid regurgitation (TR) is a risk factor for mortality in
      pulmonary hypertension (PH). TR severity varies among patients with comparable
      degrees of PH and right ventricular remodeling. The contribution of leaflet
      adaptation to the pathophysiology of TR has yet to be examined. We hypothesized
      that tricuspid leaflet area (TLA) is increased in PH, and that the adequacy of
      this increase relative to right ventricular remodeling determines TR severity.
      METHODS AND RESULTS: A prospective cohort of 255 patients with PH from pre and
      postcapillary pathogeneses was assembled from 2 centers. Patients underwent a 3
      dimensional echocardiogram focused on the tricuspid apparatus. TLA was measured
      with the Omni 4D software package. Compared with normal controls, patients with
      PH had a 2-fold increase in right ventricular volumes, 62% increase in annular
      area, and 49% increase in TLA. Those with severe TR demonstrated inadequate
      increase in TLA relative to the closure area, such that the ratio of TLA:closure
      area <1.78 was highly predictive of severe TR (odds ratio, 68.7; 95% confidence
      interval, 16.2-292.7). The median vena contracta width was 8.5 mm in the group
      with small TLA and large closure area as opposed to 4.8 mm in the group with
      large TLA and large closure area. CONCLUSIONS: TLA plays a significant role in
      determining which patients with PH develop severe functional TR. The ratio of
      TLA:closure area, reflecting the balance between leaflet adaptation versus
      annular dilation and tethering forces, is an indicator of TR severity that may
      identify which patients stand to benefit from leaflet augmentation during
      tricuspid valve repair.

PMID- 25977304
TI  - Patient selection for elective revascularization to reduce myocardial infarction
      and mortality: new lessons from randomized trials, coronary physiology, and
      statistics.

PMID- 25977305
TI  - Movement, Function, Pain, and Postoperative Edema in Axillary Web Syndrome.
AB  - BACKGROUND: Axillary web syndrome (AWS) is a condition that may develop following
      breast cancer surgery and that presents as a palpable axillary cord of tissue.
      OBJECTIVE: The purposes of this study were: (1) to determine the clinical
      characteristics of AWS related to movement, function, pain, and postoperative
      edema and (2) to define the incidence of and risk factors for AWS within the
      first 3 months following breast cancer surgery. DESIGN: This was a prospective
      cohort study with a repeated-measures design. METHODS: Women who underwent breast
      cancer surgery with sentinel node biopsy or axillary lymph node dissection (N=36)
      were assessed for AWS, shoulder range of motion, function, pain, and
      postoperative edema (using girth measurements, bioimpedance, and tissue
      dielectric constant) at 2, 4, and 12 weeks. Demographic characteristics were used
      for risk analysis. RESULTS: Seventeen women (47.2%) developed AWS, and AWS
      persisted in 10 participants (27.8%) at 12 weeks. Abduction range of motion was
      significantly lower in the AWS group compared with the non-AWS group at 2 and 4
      weeks. There were no differences between groups in measurements of function,
      pain, or edema at any time point. Trunk edema measured by dielectric constant was
      present in both groups, with an incidence of 55%. Multivariate analysis
      determined lower body mass index as being significantly associated with AWS (odds
      ratio=0.86; 95% confidence interval=0.74, 1.00). LIMITATIONS: Limitations
      included a short follow-up time and a small sample size. CONCLUSION: Axillary web
      syndrome is prevalent following breast/axilla surgery for early-stage breast
      cancer and may persist beyond 12 weeks. The early consequences include movement
      restriction, but the long-term effects of persistent AWS cords are yet unknown.
      Low body mass index is considered a risk factor for AWS.

PMID- 25977306
TI  - Common marmoset CD117+ hematopoietic cells possess multipotency.
AB  - Analysis of the hematopoiesis of non-human primates is important to clarify the
      evolution of primate-specific hematopoiesis and immune regulation. However, the
      engraftment and development of the primate hematopoietic system are well
      documented only in humans and are not clear in non-human primates. Callithrix
      jacchus (common marmoset, CM) is a New World monkey with a high rate of pregnancy
      and small size that lives in closed colonies. As stem cell factor (SCF) is an
      essential molecule for hematopoietic stem cell development in mice and humans, we
      focused on CD117, the SCF receptor, and examined whether CD117-expressing cells
      possess the hematopoietic stem/progenitor cell characteristics of newborn
      marmoset-derived hematopoietic cells that can develop into T cells and B cells.
      When CD117(+) cell fractions of the bone marrow were transplanted into
      immunodeficient NOD (non-obese diabetic)/Shi-scid, common gammac-null (NOG) mice,
      these cells engrafted efficiently in the bone marrow and spleens of the NOG mice.
      The CD117(+) cells developed into myeloid lineage cells, CD20(+) B cells and
      CD3(+) T cells, which could express CM cytokines in vivo. The development of B
      cells did not precede that of T cells. The development of CD8(+) T cells was
      dominant in NOG mice. The engraftment was comparable for both CD117(+)CD34(+)
      cells and CD117(+)CD34(-) cells. These results suggest that the CD117(+) cell
      fraction can differentiate into all three cell lineages, and the development of
      marmoset immunity in the xenogeneic environment follows diverse developmental
      pathways compared with human immunity. 

PMID- 25977307
TI  - Involvement of the cytoplasmic cysteine-238 of CD40 in its up-regulation of CD23
      expression and its enhancement of TLR4-triggered responses.
AB  - CD40, a member of the tumor necrosis factor receptor superfamily, plays a key
      role in both adaptive and innate immunity. Engagement of CD40 with its natural
      trimeric ligand or with cross-linked antibodies results in disulfide-linked CD40
      (dl-CD40) homodimer formation, a process mediated by the cysteine-238 residues of
      the cytoplasmic tail of CD40. The present study was designed to elucidate the
      biological relevance of cysteine-238-mediated dl-CD40 homodimers to the
      expression of CD23 on B cells and to investigate its possible involvement in the
      innate response. Our results indicate that cysteine-238-mediated dl-CD40
      homodimerization is required for CD40-induced activation of PI3-kinase/Akt
      signaling and the subsequent CD23 expression, as inhibition of dl-CD40 homodimer
      formation through a point mutation-approach specifically impairs these responses.
      Interestingly, cysteine-238-mediated dl-CD40 homodimers are also shown to play a
      crucial role in Toll-like receptor 4-induced CD23 expression, further validating
      the importance of this system in bridging innate and adaptive immune responses.
      This process also necessitates the activation of the PI3-kinase/Akt cascade.
      Thus, our results highlight new roles for CD40 and cysteine-238-mediated CD40
      homodimers in cell biology and identify a potential new target for therapeutic
      strategies against CD40-associated chronic inflammatory diseases. 

PMID- 25977308
TI  - Diabetes-related end-stage renal disease in Austria 1965-2013.
AB  - BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage renal
      disease (ESRD) in Austria, accounting for a high burden of morbidity and
      mortality. In this nationwide study, we aimed to evaluate the incidence and fate
      of patients with DKD-ESRD over time. METHODS: Data (collected annually) from the
      Austrian Dialysis- and Transplant Registry were analysed for the development of
      ESRD due to DKD from 1965 to 2013. RESULTS: Over 48 years, 8322 and 22 975
      patients with ESRD due to diabetes and non-diabetes, respectively, entered
      dialysis. While DKD-ESRD-patients were not dialysed until 1974, in 1975 seven
      type 1- and one type 2-diabetics started dialysis (1.06 per million population
      PMP). In the mid-eighties, DKD-ESRD-patients increasingly were accepted for
      dialysis (1986: 14.53 PMP, 1996: 31.16 PMP). After a peak incidence of 415
      diabetic ESRD-patients in 2006 (50.19 PMP), numbers decreased continuously
      thereafter (2013: 299 patients, 35.73 PMP). Mean age at start of dialysis
      increased over time and was lower in type 1- and higher in type 2- compared with
      non-diabetic patients. Five-year-survival-probability in two diabetic ESRD
      cohorts, starting in 2007/08 and 10 years earlier was calculated. Five-year
      survival was 28% in 1997/98 and 37.5% in 2007/08. Adjusted relative risk
      reduction was 33% (HR 0.67, CI 95% 0.57-0.78; P < 0.001). CONCLUSION: Despite a
      growing prevalence of diabetes, the incidence of diabetic ESRD has decreased
      after 2006. Five-year-survival-probability has improved over 10 years.
      Multifactorial therapeutic interventions may have resulted in this improvement.

PMID- 25977309
TI  - Activating PPARalpha prevents post-ischemic contractile dysfunction in
      hypertrophied neonatal hearts.
AB  - RATIONALE: Post-ischemic contractile dysfunction is a contributor to morbidity
      and mortality after the surgical correction of congenital heart defects in
      neonatal patients. Pre-existing hypertrophy in the newborn heart can exacerbate
      these ischemic injuries, which may partly be due to a decreased energy supply to
      the heart resulting from low fatty acid beta-oxidation rates. OBJECTIVE: We
      determined whether stimulating fatty acid beta-oxidation with GW7647, a
      peroxisome proliferator-activated receptor-alpha (PPARalpha) activator, would
      improve cardiac energy production and post-ischemic functional recovery in
      neonatal rabbit hearts subjected to volume overload-induced cardiac hypertrophy.
      METHODS AND RESULTS: Volume-overload cardiac hypertrophy was produced in 7-day
      old rabbits via an aorto-caval shunt, after which, the rabbits were treated with
      or without GW7647 (3 mg/kg per day) for 14 days. Biventricular working hearts
      were subjected to 35 minutes of aerobic perfusion, 25 minutes of global no-flow
      ischemia, and 30 minutes of aerobic reperfusion. GW7647 treatment did not prevent
      the development of cardiac hypertrophy, but did prevent the decline in left
      ventricular ejection fraction in vivo. GW7647 treatment increased cardiac fatty
      acid beta-oxidation rates before and after ischemia, which resulted in a
      significant increase in overall ATP production and an improved in vitro post
      ischemic functional recovery. A decrease in post-ischemic proton production and
      endoplasmic reticulum stress, as well as an activation of sarcoplasmic reticulum
      calcium ATPase isoform 2 and citrate synthase, was evident in GW7647-treated
      hearts. CONCLUSIONS: Stimulating fatty acid beta-oxidation in neonatal hearts may
      present a novel cardioprotective intervention to limit post-ischemic contractile
      dysfunction.

PMID- 25977310
TI  - Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National
      Collegiate Athletic Association Athletes: A Decade in Review.
AB  - BACKGROUND: The incidence and cause of sudden cardiac death (SCD) in athletes is
      debated with hypertrophic cardiomyopathy often reported as the most common cause.
      METHODS AND RESULTS: A database of all National Collegiate Athletic Association
      deaths (2003-2013) was developed. Additional information and autopsy reports were
      obtained when possible. Cause of death was adjudicated by an expert panel. There
      were 4 242 519 athlete-years (AY) and 514 total student athlete deaths. Accidents
      were the most common cause of death (257, 50%, 1:16 508 AY) followed by medical
      causes (147, 29%, 1:28 861 AY). The most common medical cause of death was SCD
      (79, 15%, 1:53 703 AY). Males were at higher risk than females 1:37 790 AY versus
      1:121 593 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9-5.5;
      P<0.00001), and black athletes were at higher risk than white athletes 1:21491 AY
      versus 1:68 354 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9-5.2;
      P<0.00001). The incidence of SCD in Division 1 male basketball athletes was
      1:5200 AY. The most common findings at autopsy were autopsy-negative sudden
      unexplained death in 16 (25%), and definitive evidence for hypertrophic
      cardiomyopathy was seen in 5 (8%). Media reports identified more deaths in higher
      divisions (87%, 61%, and 44%), whereas the percentages from the internal database
      did not vary (87%, 83%, and 89%). Insurance claims identified only 11% of SCDs.
      CONCLUSIONS: The rate of SCD in National Collegiate Athletic Association athletes
      is high, with males, black athletes, and basketball players at substantially
      higher risk. The most common finding at autopsy is autopsy-negative sudden
      unexplained death. Media reports are more likely to capture high-profile deaths,
      and insurance claims are not a reliable method for case identification.

PMID- 25977311
TI  - Characteristics and Outcomes of AKI Treated with Dialysis during Pregnancy and
      the Postpartum Period.
AB  - Acute kidney injury (AKI) is a rare complication of pregnancy, but may be
      associated with significant morbidity and mortality in young and often otherwise
      healthy women. We conducted a retrospective population-based cohort study of all
      consecutive pregnancies over a 15-year period (1997-2011) in Ontario, Canada, and
      describe the incidence and outcomes of AKI treated with dialysis during pregnancy
      or within 12 weeks of delivery. Of 1,918,789 pregnancies, 188 were complicated by
      AKI treated with dialysis (incidence: 1 per 10,000 [95% confidence interval, 0.8
      to 1.1]). Only 21 of 188 (11.2%) women had record of a preexisting medical
      condition; however, 130 (69.2%) women experienced a major pregnancy-related
      complication, including preeclampsia, thrombotic microangiopathy, heart failure,
      sepsis, or postpartum hemorrhage. Eight women died (4.3% versus 0.01% in the
      general population), and seven (3.9%) women remained dialysis dependent 4 months
      after delivery. Low birth weight (<2500 g), small for gestational age, or preterm
      birth (<37 weeks' gestation) were more common in pregnancies in which dialysis
      was initiated (35.6% versus 14.0%; relative risk, 3.40; 95% confidence interval,
      2.52 to 4.58). There were no stillbirths and fewer than five neonatal deaths
      (<2.7%) in affected pregnancies compared with 0.1% and 0.8%, respectively, in the
      general population. In conclusion, AKI treated with dialysis during pregnancy is
      rare and typically occurs in healthy women who acquire a major pregnancy-related
      medical condition such as preeclampsia. Many affected women and their babies have
      good short-term outcomes. 

PMID- 25977314
TI  - Taking complaints seriously: using the patient safety lens.

PMID- 25977312
TI  - Renal Production, Uptake, and Handling of Circulating alphaKlotho.
AB  - alphaKlotho is a multifunctional protein highly expressed in the kidney. Soluble
      alphaKlotho is released through cleavage of the extracellular domain from
      membrane alphaKlotho by secretases to function as an endocrine/paracrine
      substance. The role of the kidney in circulating alphaKlotho production and
      handling is incompletely understood, however. Here, we found higher alphaKlotho
      concentration in suprarenal compared with infrarenal inferior vena cava in both
      rats and humans. In rats, serum alphaKlotho concentration dropped precipitously
      after bilateral nephrectomy or upon treatment with inhibitors of alphaKlotho
      extracellular domain shedding. Furthermore, the serum half-life of exogenous
      alphaKlotho in anephric rats was four- to five-fold longer than that in normal
      rats, and exogenously injected labeled recombinant alphaKlotho was detected in
      the kidney and in urine of rats. Both in vivo (micropuncture) and in vitro
      (proximal tubule cell line) studies showed that alphaKlotho traffics from the
      basal to the apical side of the proximal tubule via transcytosis. Thus, we
      conclude that the kidney has dual roles in alphaKlotho homeostasis, producing and
      releasing alphaKlotho into the circulation and clearing alphaKlotho from the
      blood into the urinary lumen. 

PMID- 25977315
TI  - Pseudo-understanding: an analysis of the dilution of value in healthcare.
AB  - BACKGROUND: Management concepts cycle through healthcare in trends lasting 3-5
      years. This may hinder policy-makers, healthcare managers, researchers and
      clinicians from grasping the intricacies of a management concept and prevent
      organisations from realising the potential of these concepts. We, therefore,
      sought to characterise how the newest management concept, value-based healthcare
      (VBHC), is used and understood in the scientific literature. METHODS: We
      developed a novel five-step approach: (1) identification of a trend-starting
      article, (2) identification of key conceptual aspects in the trend-starting
      article, (3) collection of citing articles and identification of citing text, (4)
      categorisation of citing text to evaluate which aspects were used and (5)
      categorisation of citing text according to the structure of observed learning
      outcomes (SOLO) taxonomy to evaluate understanding. RESULTS: We identified four
      aspects in the trend-starting article, 'What is value in healthcare', of which
      value and outcomes were the most cited. More than one-quarter of the citing texts
      demonstrated no understanding of the aspect referred to; most demonstrated a
      superficial understanding. Level of understanding was inversely related to
      journal impact factor (IF), and did not change significantly over time. A deeper
      understanding was demonstrated in those articles that repeatedly cited the trend
      starting article. CONCLUSIONS: None of the four aspects were understood at a
      level required to develop the management concept of VBHC. VBHC may be undergoing
      a process of dilution rather than diffusion. To break the cycle of management
      trends, we encourage a deeper reflective process about the translation of
      management concepts in healthcare.

PMID- 25977313
TI  - The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive
      Humans.
AB  - The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact
      to maintain sodium balance. High NaCl intake increases renal synthesis of
      dopamine and dopaminergic receptor activity, decreasing epithelial sodium
      transport, whereas sodium deficit activates the RAAS, increasing epithelial
      sodium transport. We tested the hypothesis that attenuation of the natriuretic
      effect of dopamine D1-like receptors during salt restriction results in part from
      increased RAAS activity in seven salt-resistant normotensive adults using a
      double-blind placebo-controlled balanced crossover design. All subjects attained
      sodium balance on low (50 mmol Na(+)/day) and high (300 mmol Na(+)/day) NaCl
      diets, administered 4 weeks apart. Sodium, potassium, lithium, para
      aminohippurate, and creatinine clearances were measured before, during, and after
      a 3-hour infusion of fenoldopam, a D1-like receptor agonist, with and without
      pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the
      high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition
      of renal proximal and distal tubule sodium transport. On the low NaCl diet,
      fenoldopam decreased renal distal tubule sodium transport but did not cause
      natriuresis. The addition of enalapril to fenoldopam restored the natriuretic
      effect of fenoldopam and its inhibitory effect on proximal tubule sodium
      transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting
      renal proximal and distal tubule transport, but on a low NaCl diet the increased
      RAAS activity prevents the D1-like receptor from inhibiting renal proximal tubule
      sodium transport, neutralizing the natriuretic effect of fenoldopam. These
      results demonstrate an interaction between the renin-angiotensin and renal
      dopaminergic systems in humans and highlight the influence of dietary NaCl on
      these interactions. 

PMID- 25977316
TI  - New insights into orthostatic hypotension in multiple system atrophy: a European
      multicentre cohort study.
AB  - OBJECTIVES: Orthostatic hypotension (OH) is a key feature of multiple system
      atrophy (MSA), a fatal progressive neurodegenerative disorder associated with
      autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the
      clinical spectrum of OH in a large European cohort of patients with MSA and (2)
      to investigate whether a prolonged postural challenge increases the sensitivity
      to detect OH in MSA. METHODS: Assessment of OH during a 10 min orthostatic test
      in 349 patients with MSA from seven centres of the European MSA-Study Group (age:
      63.6 +/- 8.8 years; disease duration: 4.2 +/- 2.6 years). Assessment of a
      possible relationship between OH and MSA subtype (P with predominant parkinsonism
      or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS)
      scores and drug intake. RESULTS: 187 patients (54%) had moderate (> 20 mm Hg
      (systolic blood pressure (SBP)) and/or > 10 mm Hg (diastolic blood pressure
      (DBP)) or severe OH (> 30 mm Hg (SBP) and/or > 15 mm Hg (DBP)) within 3 min and
      250 patients (72%) within 10 min. OH magnitude was significantly associated with
      disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and
      supine hypertension. OH severity was not associated with MSA subtype. Drug intake
      did not differ according to OH magnitude except for antihypertensive drugs being
      less frequently, and antihypotensive drugs more frequently, prescribed in severe
      OH. CONCLUSIONS: This is the largest study of OH in patients with MSA. Our data
      suggest that the sensitivity to pick up OH increases substantially by a prolonged
      10 min orthostatic challenge. These results will help to improve OH management
      and the design of future clinical trials.

PMID- 25977317
TI  - Individual differences in the calibration of trust in automation.
AB  - OBJECTIVE: The objective was to determine whether operators with an expectancy
      that automation is trustworthy are better at calibrating their trust to changes
      in the capabilities of automation, and if so, why. BACKGROUND: Studies suggest
      that individual differences in automation expectancy may be able to account for
      why changes in the capabilities of automation lead to a substantial change in
      trust for some, yet only a small change for others. METHOD: In a baggage
      screening task, 225 participants searched for weapons in 200 X-ray images of
      luggage. Participants were assisted by an automated decision aid exhibiting
      different levels of reliability. Measures of expectancy that automation is
      trustworthy were used in conjunction with subjective measures of trust and
      perceived reliability to identify individual differences in trust calibration.
      RESULTS: Operators with high expectancy that automation is trustworthy were more
      sensitive to changes (both increases and decreases) in automation reliability.
      This difference was eliminated by manipulating the causal attribution of
      automation errors. CONCLUSION: Attributing the cause of automation errors to
      factors external to the automation fosters an understanding of tasks and
      situations in which automation differs in reliability and may lead to more
      appropriate trust. APPLICATION: The development of interventions can lead to
      calibrated trust in automation.

PMID- 25977319
TI  - Sequential in-vehicle glance distributions: an alternative approach for analyzing
      glance data.
AB  - OBJECTIVE: The aim of this study was to illustrate how a consideration of glance
      sequences to in-vehicle tasks and their associated distributions can be
      informative. BACKGROUND: The rapid growth in the number of nomadic technologies
      and in-vehicle devices has the potential to create complex, visually intensive
      tasks for drivers that may incur long in-vehicle glances. Such glances place
      drivers at increased risk of a motor vehicle crash. METHOD: We used eye-glance
      data from a study of distraction training programs to examine the change in
      glance duration distributions across consecutive glances during the performance
      of various in-vehicle tasks. RESULTS: The sequential analysis across trained and
      untrained drivers showed that the proportion of late-sequence glances longer than
      a 2-s threshold among untrained drivers was almost double the number of such
      glances for the trained drivers, that the third and later glances were
      particularly problematic, and that training reduced the proportion of early- and
      later-sequence glances. CONCLUSION: Examining how the duration of off-road
      glances varies as a function of their order in a sequence of glances and the
      visual demands of the task can offer important insights into the change in the
      distracting potential of in-vehicle tasks across glances and the effects of
      training. APPLICATION: The sequential analysis of in-vehicle glance data can be
      useful for researchers and practitioners and has implications for the development
      and evaluation of training programs as well as for task and interface design.

PMID- 25977318
TI  - Head and trunk moments of inertia of able-bodied and unbraced scoliotic girls.
AB  - OBJECTIVE: The purposes of this study were to estimate head and trunk's (HT)
      radii of gyration (K) and moments of inertia (I) in able-bodied and unbraced
      scoliotic girls using an angular momentum method, to test if the use of mean
      ratios calculated in this study and given by de Leva present similar values
      compared to the experimental data, and to determine how these methods behave in
      estimation of scoliotic HT's K and I with variable Cobb angles. BACKGROUND:
      Scoliotic HT's I estimated from anthropometric tables can lead to error in joint
      muscle moment calculations. METHOD: Twenty-one unbraced scoliotic and 20 able
      bodied girls participated. HT's I values were calculated using an angular
      momentum method. RESULTS: Angular momentum method provided greater HT's I for the
      scoliotic group compared with the able-bodied girls. HT's I obtained by the mean
      ratios calculated from this study were close to the measured values. Compared
      with the experimental I, de Leva method provided significantly lower I in the
      scoliotic group. Scoliotic HT's K and I obtained from angular momentum method
      showed greater correlations with the Cobb angles. CONCLUSION: The use of mean
      ratios obtained in this study to estimate HT's K values in unbraced scoliotic
      girls could overcome the drawbacks of current anthropometric methods.
      APPLICATION: These results can be used to calculate more precise moments of force
      during daily activities in scoliotic girls with mild scoliosis and to improve the
      design of corrective flexible body braces prescribed in cases of rapid
      interventions in young patients of moderate spinal deformities.

PMID- 25977320
TI  - Staying in the zone: offshore drillers' situation awareness.
AB  - OBJECTIVE: The aim of this study was to identify the cognitive components
      required for offshore drillers to develop and maintain situation awareness (SA)
      while controlling subsea hydrocarbon wells. BACKGROUND: SA issues are often
      identified as contributing factors to drilling incidents, most recently in the
      Deepwater Horizon blowout. Yet, there is a limited body of research investigating
      SA in the offshore drilling environment. METHOD: In the first study, critical
      incident interviews were conducted with 18 experienced drilling personnel.
      Transcripts were subjected to theory-driven thematic analysis, producing a
      preliminary cognitive framework of how drillers develop and maintain SA during
      well control. In the second study, 24 hr of observations (in vivo and video) of
      drillers managing a high fidelity well-control simulator were analyzed to further
      develop the framework. RESULTS: The cognitive components that enable drillers to
      build up an understanding of what is happening in the wellbore and surrounding
      environment, to predict how this understanding may develop, were identified.
      These components included cue recognition, interpretation of information in
      conjunction with the current mental model, and projection through mental
      simulation. Factors such as distracters, expectations, and information sharing
      between crew members can both positively and negatively influence the drillers'
      SA. CONCLUSION: The findings give a preliminary understanding into the components
      of drillers' SA, highlighting the importance of SA for safe and effective
      performance and indicating that Endsley's model of SA can be applied to drilling.
      APPLICATION: The results have consequences for training, task management, and
      work design recommendations.

PMID- 25977321
TI  - A User-Developed 3-D Hand Gesture Set for Human-Computer Interaction.
AB  - OBJECTIVE: The purpose of this study was to develop a lexicon for 3-D hand
      gestures for common human-computer interaction (HCI) tasks by considering
      usability and effort ratings. BACKGROUND: Recent technologies create an
      opportunity for developing a free-form 3-D hand gesture lexicon for HCI. METHOD:
      Subjects (N = 30) with prior experience using 2-D gestures on touch screens
      performed 3-D gestures of their choice for 34 common HCI tasks and rated their
      gestures on preference, match, ease, and effort. Videos of the 1,300 generated
      gestures were analyzed for gesture popularity, order, and response times. Gesture
      hand postures were rated by the authors on biomechanical risk and fatigue.
      RESULTS: A final task gesture set is proposed based primarily on subjective
      ratings and hand posture risk. The different dimensions used for evaluating task
      gestures were not highly correlated and, therefore, measured different properties
      of the task-gesture match. APPLICATION: A method is proposed for generating a
      user-developed 3-D gesture lexicon for common HCIs that involves subjective
      ratings and a posture risk rating for minimizing arm and hand fatigue.

PMID- 25977322
TI  - MSSQ-Short Norms May Underestimate Highly Susceptible Individuals: Updating the
      MSSQ-Short Norms.
AB  - OBJECTIVE: The aim of this study was to provide more reliable and robust norms
      for the Motion Sickness Susceptibility Questionnaire (MSSQ-Short). BACKGROUND:
      The previous norms for the MSSQ-Short involved a small sample overrepresenting
      younger female participants, which may provide misleading estimates of
      susceptibility in the general population. METHOD: We measured MSSQ-Short scores
      in a sample of 1,711 members of the general public in New Zealand and Australia.
      The sample is 6.6 times larger than the original norm sample, and age and gender
      closely match the general population. RESULTS: Compared with the current study,
      the original norms underrepresent those of high susceptibility by a factor of
      3.6, or 0.52 standard deviations. The analysis detected higher levels of
      susceptibility in females and significantly lower susceptibility in those ages 65
      years and older. CONCLUSION: This study provides the largest sample of MSSQ-Short
      scores with more representative demographic characteristics of age and gender.
      Despite the potential for a self-selection bias toward high levels of
      susceptibility, we argue that the current norms provide more reliable and robust
      norms than the original sample. APPLICATION: These updated norms provide the
      tools for researchers and designers to evaluate the likely effect of various
      motion environments on the general population. Robust norm data can inform
      research, including general motion sickness research and environmental design.

PMID- 25977323
TI  - Alleviating simulator sickness with galvanic cutaneous stimulation.
AB  - OBJECTIVE: In a driving simulation, we investigated the efficacy of galvanic
      cutaneous stimulation (GCS) provided during curves or intermittently during the
      whole circuit to mitigate simulator syndrome (SS). BACKGROUND: The literature on
      how GCS decreases SS, although scarce, has demonstrated the effectiveness of this
      technique. Stimulation with this and similar techniques has usually been provided
      in curves or continuously during the whole circuit but never intermittently. This
      stimulation method could generate a continued activation of processes related to
      GCS mitigating SS. METHOD: Fifteen drivers (8 men; mean age = 25.5 years)
      participated in this experiment. We compared the total scores of the Simulator
      Sickness Questionnaire (SSQ) across three stimulation conditions: (a) curve GCS
      condition, whereby GCS was provided in curves; (b) intermittent GCS condition,
      whereby GCS was provided intermittently during the whole circuit; and (c) no
      stimulation condition, whereby no stimulation was provided (baseline condition).
      RESULTS: The experimental outcomes revealed that GCS decreased SS in both the
      curve and intermittent stimulation conditions. CONCLUSION: We provide evidence
      that GCS is an effective countermeasure to decrease SS. It could be applied
      indifferently in curves or intermittently during the whole circuit. APPLICATION:
      For future interventions, we recommend the use of GCS to mitigate SS with similar
      intermittent stimulation programs. These programs have a crucial advantage as
      they are easily integrated into the simulator setup without the necessity of
      generating a complicated experimental design to stimulate during the curves.

PMID- 25977324
TI  - Virtual exertions: evoking the sense of exerting forces in virtual reality using
      gestures and muscle activity.
AB  - OBJECTIVE: This study was a proof of concept for virtual exertions, a novel
      method that involves the use of body tracking and electromyography for grasping
      and moving projections of objects in virtual reality (VR). The user views objects
      in his or her hands during rehearsed co-contractions of the same agonist
      antagonist muscles normally used for the desired activities to suggest exerting
      forces. BACKGROUND: Unlike physical objects, virtual objects are images and lack
      mass. There is currently no practical physically demanding way to interact with
      virtual objects to simulate strenuous activities. METHOD: Eleven participants
      grasped and lifted similar physical and virtual objects of various weights in an
      immersive 3-D Cave Automatic Virtual Environment. Muscle activity, localized
      muscle fatigue, ratings of perceived exertions, and NASA Task Load Index were
      measured. Additionally, the relationship between levels of immersion (2-D vs. 3
      D) was studied. RESULTS: Although the overall magnitude of biceps activity and
      workload were greater in VR, muscle activity trends and fatigue patterns for
      varying weights within VR and physical conditions were the same. Perceived
      exertions for varying weights were not significantly different between VR and
      physical conditions. CONCLUSIONS: Perceived exertion levels and muscle activity
      patterns corresponded to the assigned virtual loads, which supported the
      hypothesis that the method evoked the perception of physical exertions and showed
      that the method was promising. APPLICATION: Ultimately this approach may offer
      opportunities for research and training individuals to perform strenuous
      activities under potentially safer conditions that mimic situations while seeing
      their own body and hands relative to the scene.

PMID- 25977325
TI  - Assessment of naturalistic use patterns of advanced infotainment systems.
AB  - OBJECTIVE: The objective was to examine naturalistic usage of infotainment
      systems to assess use characteristics and patterns. BACKGROUND: Infotainment
      systems continue to evolve in terms of their capabilities and information
      availability, raising concerns about their distraction potential. Assessing
      potential distraction requires understanding how challenging different tasks are
      and how frequently they occur during driving. METHOD: High-end infotainment
      system use was observed across 17 participants over a period of approximately 4
      weeks each. One of two different infotainment systems was provided to
      participants. Audio, video, and driving performance data were collected and
      observed by trained reductionists. The two infotainment systems integrated
      iPodTM, satellite radio, CD/DVD/MP3 playback, AM/FM, and, in one case, navigation
      functionalities. Systems differed in their vehicle integration and advanced
      infotainment features offered. RESULTS: The median participant interacted with
      the infotainment systems once every 4 hr (90th percentile: 6.1 interactions/hr).
      More than 50% of these interactions involved adjusting the volume. Although there
      were a few lengthy interactions, the median duration was 2.2 s (90th percentile:
      24.6 s), which required measurable visual involvement when compared to a matched
      baseline. The median total eyes-off-road time across interactions was 1 s (90th
      percentile: 11.4 s) and differed significantly across type of system interaction.
      Longer interactions tended to occur when the vehicle was stationary. CONCLUSION:
      Drivers habitually interact with infotainment systems while driving; this
      includes advanced functions. Some self-regulation was observed. APPLICATION:
      These data provide a comparison basis for use in examining driver interactions
      with future infotainment systems.

PMID- 25977326
TI  - The effectiveness of a rearview camera and parking sensor system alone and
      combined for preventing a collision with an unexpected stationary or moving
      object.
AB  - OBJECTIVE: This study measured the effectiveness of a parking sensor system, a
      rearview camera, and a sensor system combined with a camera for preventing a
      collision with a stationary or moving child-size object in the path of a backing
      vehicle. BACKGROUND: An estimated 15,000 people are injured and 210 are killed
      every year in backover crashes involving light vehicles. Cameras and sensor
      systems may help prevent these crashes. METHOD: The sample included 111 drivers
      (55 men, 56 women), including 16 in the no-technology condition, 32 in the sensor
      condition, 32 in the camera condition, and 31 in the camera-plus-sensor
      condition. A stationary or moving child-size object was surreptitiously deployed
      in the path of participants backing out of a parking stall. RESULTS: A
      significantly smaller proportion of participants in the camera condition hit the
      stationary object compared with participants in the no-technology condition;
      however, this benefit was greatly reduced when the stationary object was
      partially or completely in the shade. Significantly fewer participants hit the
      moving object than the stationary object. The percentage of participants in the
      sensor, camera, and camera-plus-sensor conditions who hit the moving object was
      not different from the no-technology condition. CONCLUSION: The camera was the
      only technology that was effective for preventing collisions with the stationary
      object. The variation in collision outcomes between the stationary- and moving
      object conditions illustrates how the effectiveness of these technologies is
      dependent on the backing situation. APPLICATION: This research can help the
      selection and development of countermeasures to prevent backovers.

PMID- 25977327
TI  - Perceptual load in different regions of the visual scene and its relevance for
      driving.
AB  - OBJECTIVE: The aim of this study was to better understand the role played by
      perceptual load, at both central and peripheral regions of the visual scene, in
      driving safety. BACKGROUND: Attention is a crucial factor in driving safety, and
      previous laboratory studies suggest that perceptual load is an important factor
      determining the efficiency of attentional selectivity. Yet, the effects of
      perceptual load on driving were never studied systematically. METHOD: Using a
      driving simulator, we orthogonally manipulated the load levels at the road
      (central load) and its sides (peripheral load), while occasionally introducing
      critical events at one of these regions. RESULTS: Perceptual load affected
      driving performance at both regions of the visual scene. Critically, the effect
      was different for central versus peripheral load: Whereas load levels on the road
      mainly affected driving speed, load levels on its sides mainly affected the
      ability to detect critical events initiating from the roadsides. Moreover, higher
      levels of peripheral load impaired performance but mainly with low levels of
      central load, replicating findings with simple letter stimuli. CONCLUSION:
      Perceptual load has a considerable effect on driving, but the nature of this
      effect depends on the region of the visual scene at which the load is introduced.
      APPLICATION: Given the observed importance of perceptual load, authors of future
      studies of driving safety should take it into account. Specifically, these
      findings suggest that our understanding of factors that may be relevant for
      driving safety would benefit from studying these factors under different levels
      of load at different regions of the visual scene.

PMID- 25977328
TI  - Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing
      Breast Cancer.
AB  - Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC)
      has been associated with the risk of developing several tumor types. Here we
      evaluate sources of variation of this biomarker and its association with breast
      cancer risk in a prospective cohort study. mtDNA copy number was measured using
      quantitative real-time PCR on PBC DNA samples from participants in the UK-based
      Breakthrough Generations Study. Temporal and assay variation was evaluated in a
      serial study of 91 women, with two blood samples collected approximately 6-years
      apart. Then, associations with breast cancer risk factors and risk were evaluated
      in 1,108 cases and 1,099 controls using a nested case-control design. In the
      serial study, mtDNA copy number showed low assay variation but large temporal
      variation [assay intraclass correlation coefficient (ICC), 79.3%-87.9%; temporal
      ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger
      age at blood collection, being premenopausal, having an older age at menopause,
      and never taking HRT, both in cases and controls. Based on measurements in a
      single blood sample taken on average 6 years before diagnosis, higher mtDNA copy
      number was associated with increased breast cancer risk [OR (95% CI) for highest
      versus lowest quartile, 1.37 (1.02-1.83); P trend = 0.007]. In conclusion, mtDNA
      copy number is associated with breast cancer risk and represents a promising
      biomarker for risk assessment. The relatively large temporal variation should be
      taken into account in future analyses.

PMID- 25977329
TI  - Macrophages Regulate the Systemic Response to DNA Damage by a Cell Nonautonomous
      Mechanism.
AB  - The DNA damage response (DDR) is a comprehensive and complex network of
      phosphorylation-mediated signaling pathways that originates endogenously from the
      DNA lesion and activates intrinsic DNA repair mechanisms. Here we describe a
      macrophage-dependent mechanism that regulates the response to DNA damage. We
      demonstrate that human monocytes, by releasing macrophage-derived HB-EGF, enhance
      DDR in neighboring cells suffering from DNA damage. Consequently, HB-EGF-treated
      cells exhibit higher double-strand break (DSB) rejoining and display lower levels
      of residual DSBs. Diethylnitrosamine (DEN) injection induce DSBs along with
      elevation in the number of macrophages and HB-EGF expression. Significantly,
      macrophage depletion or blocking HB-EGF activity results in higher levels of
      nonrepairable DSBs, suggesting that macrophages play a role in the resolution of
      DNA damage via HB-EGF. This study establishes that macrophages, acting through
      the activation of the EGFR cascade, constitute an important cell nonautonomous
      physiologic component of the DDR and points to a unique role played by immune
      cells in maintaining genome integrity.

PMID- 25977330
TI  - Enhanced MET Translation and Signaling Sustains K-Ras-Driven Proliferation under
      Anchorage-Independent Growth Conditions.
AB  - Oncogenic K-Ras mutation occurs frequently in several types of cancers, including
      pancreatic and lung cancers. Tumors with K-Ras mutation are resistant to
      chemotherapeutic drugs as well as molecular targeting agents. Although numerous
      approaches are ongoing to find effective ways to treat these tumors, there are
      still no effective therapies for K-Ras mutant cancer patients. Here we report
      that K-Ras mutant cancers are more dependent on K-Ras in anchorage-independent
      culture conditions than in monolayer culture conditions. In seeking to determine
      mechanisms that contribute to the K-Ras dependency in anchorage-independent
      culture conditions, we discovered the involvement of Met in K-Ras-dependent,
      anchorage-independent cell growth. The Met signaling pathway is enhanced and
      plays an indispensable role in anchorage-independent growth even in cells in
      which Met is not amplified. Indeed, Met expression is elevated under anchorage
      independent growth conditions and is regulated by K-Ras in a MAPK/ERK kinase
      (MEK)-dependent manner. Remarkably, in spite of a global downregulation of mRNA
      translation during anchorage-independent growth, we find that Met mRNA
      translation is specifically enhanced under these conditions. Importantly, ectopic
      expression of an active Met mutant rescues K-Ras ablation-derived growth
      suppression, indicating that K-Ras-mediated Met expression drives "K-Ras
      addiction" in anchorage-independent conditions. Our results indicate that
      enhanced Met expression and signaling is essential for anchorage-independent
      growth of K-Ras mutant cancer cells and suggests that pharmacological inhibitors
      of Met could be effective for K-Ras mutant tumor patients.

PMID- 25977331
TI  - Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti-PD-L1
      Antibodies.
AB  - Antibodies that block the interaction between programmed death ligand 1 (PD-L1)
      and PD-1 have shown impressive antitumor activity. Patients with tumors
      expressing PD-L1 are most likely to respond to this treatment. The aim of our
      study was to develop a noninvasive imaging technique to determine tumor PD-L1
      expression in vivo. This could allow selection of patients that are most likely
      to benefit from anti-PD-1/PD-L1 treatment and to monitor PD-L1 expression during
      therapy. The monoclonal antibody PD-L1.3.1 was radiolabeled with Indium-111
      ((111)In) and characterized using PD-L1-expressing MDA-MB-231 cells.
      Subsequently, the optimal antibody dose and time point for imaging was determined
      in mice with MDA-MB-231 xenografts. Finally, SPECT/CT imaging was performed in
      xenograft models with different PD-L1 expression levels and tumor sections were
      analyzed for PD-L1 expression using IHC. The optimal antibody dose of (111)In-PD
      L1.3.1 (Kd = 1 nmol/L) for SPECT/CT imaging was <=1 MUg. Highest tumor-to-normal
      tissue contrast was obtained at days 3 and 7 after injection. (111)In-PD-L1.3.1
      SPECT/CT showed efficient accumulation in high PD-L1-expressing tumors (MDA-MB
      231 and SK-Br-3), whereas no specific uptake was observed in tumors with low or
      no detectable levels of PD-L1 (SUM149, BT474, and MCF-7). SPECT/CT and
      autoradiography showed a very heterogeneous distribution of (111)In-PD-L1.3.1
      within the tumor. In conclusion, this is the first study showing the feasibility
      of noninvasive in vivo imaging of PD-L1 expression in tumors. (111)In-PD-L1.3.1
      showed efficient and specific uptake in PD-L1 expressing xenografts. This
      technique may enable patient selection for PD-1 and PD-L1-targeted therapy.

PMID- 25977333
TI  - Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by
      Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes.
AB  - Reciprocal interactions between tumor cells and their microenvironment vitally
      impact tumor progression. In this study, we show that GM-CSF produced by primary
      breast tumor cells induced the activation of plasmacytoid predendritic cells
      (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF
      receptor were increased in breast tumors compared with noninvolved adjacent
      breast tissue. Tumor-activated pDC acquired naive CD4(+) T-cell stimulatory
      capacity and promoted a regulatory Th2 response. Finally, the concomitant
      increase of GM-CSF and pDC was significantly associated with relatively more
      aggressive breast cancer subtypes. Our results characterize the first tumor
      derived factor that can activate pDC to promote a regulatory Th2 response, with
      implications for therapeutic targeting of a tumor-immune axis of growing
      recognition in its significance to cancer.

PMID- 25977334
TI  - Secalonic Acid-D Represses HIF1alpha/VEGF-Mediated Angiogenesis by Regulating the
      Akt/mTOR/p70S6K Signaling Cascade.
AB  - Tumor angiogenesis is a validated target for therapeutic intervention, but agents
      that are more disease selective are needed. Here, we report the isolation of
      secalonic acid-D (SAD), a mycotoxin from a novel source that exhibits potent
      antiangiogenic antitumor activity. SAD inhibited multiple HIF1alpha/VEGF
      arbitrated angiogenesis dynamics as scored in human umbilical vascular
      endothelial cells and human MCF-7 breast tumor xenografts. Similarly, SAD
      suppressed VEGF-induced microvessel sprouting from rat aortic ring and blood
      vessel formation in the Matrigel plug assay in C57/BL6J mice. Under normoxic or
      hypoxic conditions, SAD inhibited cell survival through the Akt/mTOR/p70S6K
      pathway, with attendant effects on key proangiogenesis factors, including
      HIF1alpha, VEGFR, and MMP-2/MMP-9. These effects were reversed by cotreatment
      with the Akt inhibitors perifosine and GSK69069 or by the addition of
      neutralizing VEGF antibodies. The apoptotic properties of SAD were determined to
      be both extrinsic and intrinsic in nature, whereas the cell-cycle inhibitory
      effects were mediated by altering the level of key G1-S transition-phase
      proteins. In experimental mouse models of breast cancer, SAD dosing produced no
      apparent toxicities (either orally or intraperitoneal) at levels that yielded
      antitumor effects. Taken together, our findings offered a preclinical validation
      and mechanistic definition of the antiangiogenic activity of a novel mycotoxin,
      with potential application as a cancer-selective therapeutic agent.

PMID- 25977332
TI  - Pharmacological Inhibition of beta3 Integrin Reduces the Inflammatory Toxicities
      Caused by Oncolytic Adenovirus without Compromising Anticancer Activity.
AB  - Adenoviruses have been clinically tested as anticancer therapies but their
      utility has been severely limited by rapid, systemic cytokine release and
      consequent inflammatory toxicity. Here, we describe a new approach to tackling
      these dangerous side effects. Using human ovarian cancer cell lines as well as
      malignant epithelial cells harvested from the ascites of women with ovarian
      cancer, we show that tumor cells do not produce cytokines in the first 24 hours
      following in vitro infection with the oncolytic adenovirus dl922-947. In
      contrast, dl922-947 does induce inflammatory cytokines at early time points
      following intraperitoneal delivery in mice with human ovarian cancer
      intraperitoneal xenografts. In these animals, cytokines originate predominantly
      in murine tissues, especially in macrophage-rich organs such as the spleen. We
      use a nonreplicating adenovirus to confirm that early cytokine production is
      independent of adenoviral replication. Using beta3 integrin knockout mice
      injected intraperitoneally with dl922-947 and beta3 null murine peritoneal
      macrophages, we confirm a role for macrophage cell surface beta3 integrin in this
      dl922-947-induced inflammation. We present new evidence that co-administration of
      a cyclic RGD-mimetic-specific inhibitor of beta3 integrin significantly
      attenuates the cytokine release and inflammatory hepatic toxicity induced by
      dl922-947 in an intraperitoneal murine model of ovarian cancer. Importantly, we
      find no evidence that beta3 inhibition compromises viral infectivity and
      oncolysis in vitro or anticancer efficacy in vivo. By enabling safe, systemic
      delivery of replicating adenoviruses, this novel approach could have a major
      impact on the future development of these effective anticancer agents.

PMID- 25977335
TI  - Targeting Pancreatic Cancer Metastasis by Inhibition of Vav1, a Driver of Tumor
      Cell Invasion.
AB  - Pancreatic cancer, one of the most lethal forms of human cancer, is largely
      resistant to many conventional chemotherapeutic agents. Although many therapeutic
      approaches focus on tumor growth, metastasis is a primary factor contributing to
      lethality. Therefore, novel therapies to target metastatic invasion could prevent
      tumor spread and recurrence resulting from local and distant metastasis. The
      protein Vav1 is aberrantly expressed in more than half of pancreatic cancers. Its
      expression promotes activation of Rac and Cdc42 and leads to enhanced invasion
      and migration, as well as increased tumor cell survival and proliferation,
      suggesting that Vav1 could be a potent therapeutic target for pancreatic cancer.
      The purine analogue azathioprine, well known for its function as an anti
      inflammatory compound, was recently shown to function by inhibiting Vav1
      signaling in immune cells. We therefore hypothesized that azathioprine could also
      inhibit Vav1 in pancreatic tumor cells to reduce its proinvasive functions.
      Indeed, we have found that treatment of cultured pancreatic tumor cells with
      azathioprine inhibited Vav1-dependent invasive cell migration and matrix
      degradation, through inhibition of Rac and Cdc42 signaling. Furthermore,
      azathioprine treatment decreased metastasis in both xenograft and genetic mouse
      models of pancreatic cancer. Strikingly, metastasis was dramatically reduced in
      Vav1-expressing tumors arising from p48(Cre/+), Kras(G12D/+), p53(F/+) mice.
      These inhibitory effects were mediated through Vav1, as Vav1-negative cell lines
      and tumors were largely resistant to azathioprine treatment. These findings
      demonstrate that azathioprine and related compounds could be potent
      antimetastatic agents for Vav1-positive pancreatic tumors.

PMID- 25977336
TI  - NKX3.1 Suppresses TMPRSS2-ERG Gene Rearrangement and Mediates Repair of Androgen
      Receptor-Induced DNA Damage.
AB  - TMPRSS2 gene rearrangements occur at DNA breaks formed during androgen receptor
      mediated transcription and activate expression of ETS transcription factors at
      the early stages of more than half of prostate cancers. NKX3.1, a prostate tumor
      suppressor that accelerates the DNA repair response, binds to androgen receptor
      at the ERG gene breakpoint and inhibits both the juxtaposition of the TMPRSS2 and
      ERG gene loci and also their recombination. NKX3.1 acts by accelerating DNA
      repair after androgen-induced transcriptional activation. NKX3.1 influences the
      recruitment of proteins that promote homology-directed DNA repair. Loss of NKX3.1
      favors recruitment to the ERG gene breakpoint of proteins that promote error
      prone nonhomologous end-joining. Analysis of prostate cancer tissues showed that
      the presence of a TMPRSS2-ERG rearrangement was highly correlated with lower
      levels of NKX3.1 expression consistent with the role of NKX3.1 as a suppressor of
      the pathogenic gene rearrangement.

PMID- 25977337
TI  - Blocking Tumor Necrosis Factor alpha Enhances CD8 T-cell-Dependent Immunity in
      Experimental Melanoma.
AB  - TNF plays a dual, still enigmatic role in melanoma, either acting as a cytotoxic
      cytokine or favoring a tumorigenic inflammatory microenvironment. Herein, the
      tumor growth of melanoma cell lines expressing major histocompatibility complex
      class I molecules at high levels (MHC-I(high)) was dramatically impaired in TNF
      deficient mice, and this was associated with enhanced tumor-infiltrating CD8(+) T
      lymphocytes. Immunodepletion of CD8 T cells fully restored melanoma growth in
      TNF(-/-) mice. Systemic administration of Etanercept inhibited MHC-I(high)
      melanoma growth in immunocompetent but not in immunodeficient (IFNgamma(-/-),
      nude, or CD8(-/-)) mice. MHC-I(high) melanoma growth was also reduced in mice
      lacking TNF-R1, but not TNF-R2. TNF(-/-) and TNF-R1(-/-) mice as well as
      Etanercept-treated WT mice displayed enhanced intratumor content of high
      endothelial venules surrounded by high CD8(+) T-cell density. Adoptive transfer
      of activated TNF-R1-deficient or -proficient CD8(+) T cells in CD8-deficient mice
      bearing B16K1 tumors demonstrated that TNF-R1 deficiency facilitates the
      accumulation of live CD8(+) T cells into the tumors. Moreover, in vitro
      experiments indicated that TNF triggered activated CD8(+) T cell death in a TNF
      R1-dependent manner, likely limiting the accumulation of tumor-infiltrating
      CD8(+) T cells in TNF/TNF-R1-proficient animals. Collectively, our observations
      indicate that TNF-R1-dependent TNF signaling impairs tumor-infiltrating CD8(+) T
      cell accumulation and may serve as a putative target to favor CD8(+) T-cell
      dependent immune response in melanoma.

PMID- 25977339
TI  - Drug combination studies and their synergy quantification using the Chou-Talalay
      method--letter.

PMID- 25977338
TI  - miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of
      Matrix Metalloproteinase-14.
AB  - Upregulation of matrix metalloproteinase MMP-14 (MT1-MMP) is associated with poor
      prognosis in cancer patients, but it is unclear how MMP-14 becomes elevated in
      tumors. Here, we show that miR-181a-5p is downregulated in aggressive human
      breast and colon cancers where its levels correlate inversely with MMP-14
      expression. In clinical specimens, enhanced expression of MMP-14 was observed in
      cancer cells located at the invasive front of tumors where miR-181a-5p was
      downregulated relative to adjacent normal cells. Bioinformatics analyses defined
      a potential miR-181a-5p response element within the 3'-untranslated region of MMP
      14 that was validated in reporter gene experiments. Ectopic miR-181a-5p reduced
      MMP-14 expression, whereas miR-181a-5p attenuation elevated MMP-14 expression. In
      support of a critical relationship between these two genes, miR-181a-5p-mediated
      reduction of MMP-14 levels was sufficient to decrease cancer cell migration,
      invasion, and activation of pro-MMP-2. Furthermore, this reduction in MMP-14
      levels was sufficient to reduce in vivo invasion and angiogenesis in chick
      chorioallantoic membrane assays. Taken together, our results establish the
      regulation of MMP-14 in cancers by miR-181a-5p through a posttranscriptional
      mechanism, and they further suggest strategies to elevate miR-181a-5p to prevent
      cancer metastasis.

PMID- 25977340
TI  - Classifying Cancers Based on T-cell Infiltration and PD-L1.
AB  - Cancer immunotherapy may become a major treatment backbone in many cancers over
      the next decade. There are numerous immune cell types found in cancers and many
      components of an immune reaction to cancer. Thus, the tumor has many strategies
      to evade an immune response. It has been proposed that four different types of
      tumor microenvironment exist based on the presence or absence of tumor
      infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. We
      review this stratification and the latest in a series of results that shed light
      on new approaches for rationally designing ideal combination cancer therapies
      based on tumor immunology.

PMID- 25977341
TI  - PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE
      Exposure.
AB  - PURPOSE: The carcinogenic capacity of B[a]P/B[a]PDE is supported by epidemiologic
      studies. However, the molecular mechanisms responsible for B[a]P/B[a]PDE-caused
      lung cancer have not been well investigated. We evaluated here the role of novel
      target PHLPP2 in lung inflammation and carcinogenesis upon B[a]P/B[a]PDE
      exposure. EXPERIMENTAL DESIGN: We used the Western blotting, RT-PCR,
      [(35)S]methionine pulse and immunohistochemistry staining to determine PHLPP2
      downregulation following B[a]P/B[a]PDE exposure. Both B[a]PDE-induced Beas-2B
      cell transformation model and B[a]P-caused mouse lung cancer model were used to
      elucidate the mechanisms leading to PHLPP2 downregulation and lung
      carcinogenesis. The important findings were also extended to in vivo human
      studies. RESULTS: We found that B[a]P/B[a]PDE exposure downregulated PHLPP2
      expression in human lung epithelial cells in vitro and in mouse lung tissues in
      vivo. The ectopic expression of PHLPP2 dramatically inhibited cell transformation
      upon B[a]PDE exposure. Mechanistic studies showed that miR-205 induction was
      crucial for inhibition of PHLPP2 protein translation by targeting PHLPP2-3'-UTR.
      Interestingly, PHLPP2 expression was inversely associated with tumor necrosis
      factor alpha (TNFalpha) expression, with low PHLPP2 and high TNFalpha expression
      in lung cancer tissues compared with the paired adjacent normal lung tissues.
      Additional studies revealed that PHLPP2 exhibited its antitumorigenic effect of
      B[a]P/B[a]PDE through the repression of inflammatory TNFalpha transcription.
      CONCLUSIONS: Our studies not only first time identify PHLPP2 downregulation by
      lung carcinogen B[a]P/B[a]PDE, but also elucidate a novel molecular mechanisms
      underlying lung inflammation and carcinogenesis upon B[a]P/B[a]PDE exposure.

PMID- 25977342
TI  - High Serum Transforming Growth Factor-beta1 Levels Predict Outcome in
      Hepatocellular Carcinoma Patients Treated with Sorafenib.
AB  - BACKGROUND: The TGF-beta signaling pathway is crucial in the progression and
      metastasis of malignancies. We investigated whether the serum TGF-beta1 level was
      related to the outcomes of patients treated with sorafenib for advanced
      hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: We selected patients who had
      received sorafenib-containing regimens as first-line therapy for advanced HCC
      between 2007 and 2012. Serum TGF-beta1 levels were measured and correlated with
      the treatment outcomes. The expression TGF-beta1 and the sensitivity to sorafenib
      were examined in HCC cell lines. RESULTS: Ninety-one patients were included; 62
      (68%) were hepatitis B virus surface antigen (+), and 11 (12%) were anti
      hepatitis C virus (+). High (>= median) pretreatment serum TGF-beta1 levels
      (median 13.7 ng/mL; range, 3.0-41.8) were associated with high alpha-fetoprotein
      levels, but not with age, gender, or disease stage. Patients with high
      pretreatment serum TGF-beta1 levels exhibited significantly shorter progression
      free survival (median, 2.5 vs. 4.3 months; P = 0.022) and overall survival
      (median 5.6 vs. 11.6 months; P = 0.029) than did patients with low serum TGF
      beta1 levels. Compared with pretreatment levels, the serum TGF-beta1 levels were
      significantly increased at disease progression (n = 29, P = 0.010). In
      preclinical models of HCC, higher TGF-beta1 expression levels were associated
      with poorer sensitivity to sorafenib. CONCLUSIONS: High pretreatment serum TGF
      beta1 levels were associated with poor prognoses, and increased serum TGF-beta1
      levels were associated with the disease progression of advanced HCC patients. TGF
      beta pathway may be explored as a therapeutic target for advanced HCC.

PMID- 25977344
TI  - Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in
      Patients with Advanced Solid Tumors.
AB  - PURPOSE: This phase I study evaluated the safety, maximum tolerated dose,
      antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in
      patients with advanced solid tumors. EXPERIMENTAL DESIGN: In a 3 + 3 dose
      escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg
      intravenously every 2 weeks until progression or intolerable toxicity. Seven
      additional patients received 10 mg/kg every 2 weeks. Thirteen patients
      participated in a 3-week intrapatient dose escalation (dose range, 0.005-10
      mg/kg) followed by 2 or 10 mg/kg every 3 weeks. Tumor response was assessed by
      Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: No
      dose-limiting toxicities were observed. Maximum administered dose was 10 mg/kg
      every 2 weeks. One patient with melanoma and one with Merkel cell carcinoma
      experienced complete responses of 57 and 56+ weeks' duration, respectively. Three
      patients with melanoma experienced partial responses. Fifteen patients with
      various malignancies experienced stable disease. One patient died of cryptococcal
      infection 92 days after pembrolizumab discontinuation, following prolonged
      corticosteroid use for grade 2 gastritis considered drug related. Pembrolizumab
      exhibited pharmacokinetic characteristics typical of humanized monoclonal
      antibodies. Maximum serum target engagement was reached with trough levels of
      doses greater than or equal to 1 mg/kg every 3 weeks. Mechanism-based
      translational models with a focus on intratumor exposure prediction suggested
      robust clinical activity would be observed at doses >=2 mg/kg every 3 weeks.
      CONCLUSIONS: Pembrolizumab was well tolerated and associated with durable
      antitumor activity in multiple solid tumors. The lowest dose with full potential
      for antitumor activity was 2 mg/kg every 3 weeks.

PMID- 25977343
TI  - MEK Inhibitor PD-0325901 Overcomes Resistance to PI3K/mTOR Inhibitor PF-5212384
      and Potentiates Antitumor Effects in Human Head and Neck Squamous Cell Carcinoma.
AB  - PURPOSE: Head and neck squamous cell carcinomas exhibit variable sensitivity to
      inhibitors of the PI3K/mTOR pathway, an important target of genomic alterations
      in this cancer type. The mitogen-activated protein kinase kinase
      (MEK)/ERK/activator protein 1 (AP-1) and nuclear factor-kappaB (NF-kappaB)
      pathways are also frequently co-activated, but their roles in resistance
      mechanisms to PI3K/mTOR inhibitors and as therapeutic targets in head and neck
      squamous cell carcinoma (HNSCC) are not well defined. EXPERIMENTAL DESIGN: We
      determined the IC50s of dual PI3K/mTOR inhibitor PF-05212384 (PF-384) by XTT
      assays in 14 HNSCC lines with PI3K/Akt/mTOR cascade alterations. In two resistant
      models, we further characterized the molecular, cellular, and in vivo attributes
      and effects of combining PF-384 with MEK inhibitor PD-0325901 (PD-901). RESULTS:
      PF-384 IC50s varied between 0.75 and 133 nmol/L in 14 HNSCC lines with
      overexpression or mutations of PIK3CA, and sensitivity correlated with increased
      phospho-AKT(T308/S473). In resistant UMSCC-1 and -46 models, PF-384 increased G0
      /G1-phase accumulation but weakly induced sub-G0 cell death. PF-384 inhibited
      direct targets of PI3K/mTOR, but incompletely attenuated co-activated ERK and
      UMSCC-1 xenograft growth in vivo. PD-901 strongly inhibited MEK/ERK targets, and
      the combination of PF-384 and PD-901 inhibited downstream NF-kappaB and AP-1
      transactivation, and IL8 and VEGF production in vitro. PD-901 potently inhibited
      tumor growth alone and with PF384, enhanced antiproliferative, apoptotic, and
      anti-angiogenesis activity in vivo. CONCLUSIONS: PI3K/mTOR inhibitor PF-384
      exhibits variable activity in a panel of HNSCC cell lines with differing PIK3CA
      expression and mutation status. MEK inhibitor PD-901 overcomes resistance and
      enhances antitumor effects observed with PF-384 in vivo.

PMID- 25977346
TI  - A look at firesetting, arson, and pyromania.

PMID- 25977345
TI  - Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute
      GVHD While Preserving GVT Effects.
AB  - PURPOSE: Immune-mediated graft-versus-tumor (GVT) effects can occur after
      allogeneic hematopoietic stem cell transplantation (HSCT), but GVT is tightly
      linked to its main complication, graft-versus-host disease (GVHD). Strategies
      aimed at modulating GVHD, while maintaining the GVT effect, are needed to improve
      the cure rate of transplant. Given the emerging role of Janus-activated kinase
      (JAK) signaling in lymphoproliferative and myeloproliferative diseases and its
      established function at dictating T-cell differentiation, we postulated that JAKs
      might be potential therapeutic targets through a pharmacologic approach.
      EXPERIMENTAL DESIGN: We examined the effect of JAK1/JAK2 modulation by
      ruxolitinib in a mouse model of fully MHC mismatched bone marrow transplant
      comprising in vivo tumor inoculation. RESULTS: JAK1/JAK2 inhibition by
      ruxolitinib improved both overall survival (P = 0.03) and acute GVHD pathologic
      score at target organs (P <= 0.001) of treated mice. In addition, treatment with
      ruxolitinib was associated with a preserved GVT effect, as evidenced by reduction
      of tumor burden (P = 0.001) and increase of survival time (P = 0.01). JAK1/JAK2
      inhibition did not impair the in vivo acquisition of donor T-cell alloreactivity;
      this observation may account, at least in part, to the preserved GVT effect.
      Rather, JAK1/JAK2 inhibition of GVHD was associated with the modulation of
      chemokine receptor expression, which may have been one factor in the reduced
      infiltration of donor T cells in GVHD target organs. CONCLUSIONS: These data
      provide further evidence that JAK inhibition represents a new and potentially
      clinically relevant approach to GVHD prevention.

PMID- 25977347
TI  - Radon exhalation from sub-slab aggregate used in home construction in Canada.
AB  - Exposure to elevated levels of radon in homes has been shown to result in an
      increased risk of developing lung cancer. The two largest contributors to indoor
      radon are radon in soil gas, formed from the rocks and soil surrounding the home,
      and building materials such as aggregate. This study measured the surface radon
      exhalation rates for 35 aggregate samples collected from producers across Canada.
      The radon exhalation rates ranged from 2.3 to 479.9 Bq m(-2) d(-1), with a mean
      of 80.7+/-112 Bq m(-2) d(-1). Using a simple, conservative analysis, the
      aggregate contribution to radon concentrations in an unfinished basement was
      determined. The maximum estimated radon concentration was 32.5+/-2.7 Bq m(-3), or
      ~16 % of the Canadian Radon Guideline. It can be concluded that under normal
      conditions radon exhalation from aggregate contributes very little to the total
      radon concentration in indoor air.

PMID- 25977348
TI  - Doses metrics and patient age in CT.
AB  - The aim of this study was to investigate how effective dose and size-specific
      dose estimate (SSDE) change with patient age (size) for routine head and
      abdominal/pelvic CT examinations. Heads and abdomens of patients were modelled as
      a mass-equivalent cylinder of water corresponding to the patient 'effective
      diameter'. Head CT scans were performed at CTDIvol(S) of 40 mGy, and abdominal CT
      scans were performed at CTDIvol(L) of 10 mGy. Values of SSDE were obtained using
      conversion factors in AAPM Task Group Report 204. Age-specific scan lengths for
      head and abdominal CT scans obtained from the authors' clinical practice were
      used to estimate the dose-length product for each CT examination. Effective doses
      were calculated from previously published age- and sex-specific E/DLP conversion
      factors, based on ICRP 103 organ-weighting factors. For head CT examinations, the
      scan length increased from 15 cm in a newborn to 20 cm in adults, and for an
      abdominal/pelvic CT, the scan length increased from 20 cm in a newborn to 45 cm
      in adults. For head CT scans, SSDE ranged from 37.2 mGy in adults to 48.8 mGy in
      a newborn, an increase of 31 %. The corresponding head CT effective doses range
      from 1.4 mSv in adults to 5.2 mSv in a newborn, an increase of 270 %. For abdomen
      CT scans, SSDE ranged from 13.7 mGy in adults to 23.0 mGy in a newborn, an
      increase of 68 %. The corresponding abdominal CT effective doses ranged from 6.3
      mSv in adults to 15.4 mSv in a newborn, an increase of 140 %. SSDE increases much
      less than effective dose in paediatric patients compared with adults because it
      does not account for scan length or scattered radiation. Size- and age-specific
      effective doses better quantify the total radiation received by patients in CT by
      explicitly accounting for all organ doses, as well as their relative radio
      sensitivity. 

PMID- 25977349
TI  - A new large-volume metal reference standard for radioactive waste management.
AB  - A new large-volume metal reference standard has been developed. The intended use
      is for calibration of free-release radioactivity measurement systems and is made
      up of cast iron tubes placed inside a box of the size of a Euro-pallet (80 * 120
      cm). The tubes contain certified activity concentrations of (60)Co (0.290 +/-
      0.006 Bq g(-1)) and (110m)Ag (3.05 +/- 0.09 Bq g(-1)) (reference date: 30
      September 2013). They were produced using centrifugal casting from a smelt into
      which (60)Co was first added and then one piece of neutron irradiated silver wire
      was progressively diluted. The iron castings were machined to the desirable
      dimensions. The final material consists of 12 iron tubes of 20 cm outer diameter,
      17.6 cm inner diameter, 40 cm length/height and 245.9 kg total mass. This paper
      describes the reference standard and the process of determining the reference
      activity values.

PMID- 25977350
TI  - Low air exchange rate causes high indoor radon concentration in energy-efficient
      buildings.
AB  - Since 1995, requirements on energy-efficient building construction were
      established in Russian Building Codes. In the course of time, utilisation of such
      technologies became prevailing, especially in multi-storey building construction.
      According to the results of radon survey in buildings constructed meeting new
      requirements on energy efficiency, radon concentration exceeds the average level
      in early-constructed buildings. Preponderance of the diffusion mechanism of radon
      entry in modern multi-storey buildings has been experimentally established. The
      experimental technique of the assessment of ventilation rate in dwellings under
      real conditions was developed. Based on estimates of average ventilation rate, it
      was approved that measures to increase energy efficiency lead to reduction in
      ventilation rate and accumulation of higher radon concentrations indoors.
      Obtained ventilation rate values have to be considered as extremely low. 

PMID- 25977351
TI  - Calibration system for measuring the radon flux density.
AB  - The measurement of radon flux from soil surface is the useful tool for the
      assessment of radon-prone areas and monitoring of radon releases from uranium
      mining and milling residues. The accumulation chambers with hollow headspace and
      chambers with activated charcoal are the most used devices for these purposes.
      Systematic errors of the measurements strongly depend on the geometry of the
      chamber and diffusion coefficient of the radon in soil. The calibration system
      for the attestation of devices for radon flux measurements was constructed. The
      calibration measurements of accumulation chambers and chambers with activated
      charcoal were conducted. The good agreement between the results of 2D modelling
      of radon flux and measurements results was observed. It was demonstrated that
      reliable measurements of radon flux can be obtained by chambers with activated
      charcoal (equivalent volume ~75 l) or by accumulation chambers with hollow
      headspace of ~7-10 l and volume/surface ratio (height) of >15 cm.

PMID- 25977352
TI  - Radon transport: laboratory and model study.
AB  - In order to exploit radon profiles for geophysical purposes and also to estimate
      its entry indoors, it is necessary to study its transport through porous soils.
      The great number of involved parameters and processes affecting the emanation of
      radon from the soil grains and its transport in the source medium has led to many
      theoretical and/or laboratory studies. The authors report the first results of a
      laboratory study carried out at the Radioactivity Laboratory of the Department of
      Physics and Astronomy (University of Catania) by means of a facility for
      measuring radon concentrations in the sample pores at various depths under well
      defined and controlled conditions of physical parameters. In particular, radon
      concentration vertical profiles extracted in low-moisture samples for different
      advective fluxes and temperatures were compared with expected concentrations,
      according to a three-phase transport model developed by Andersen (Riso National
      Laboratory, Denmark), showing, in general, a good agreement between measurements
      and model calculations. 

PMID- 25977353
TI  - Soil radioactivity measurements and estimation of radon/thoron exhalation rate in
      soil samples from Kalpakkam residential complex.
AB  - The objective of this study is to compute the primordial radionuclides activity
      in soil samples and estimate the radon/thoron exhalation rates. A total of 25
      locations were chosen for the study at Kalpakkam. Ambient radiation levels were
      monitored prior to collection of samples, which were subjected to gamma
      spectrometry. While (238)U concentration was found to be below detectable limit,
      the activities of (232)Th and (40)K were varying from 34.53 to 1093.11 Bq kg(-1)
      and 36.6 to 570.08 Bq kg(-1), respectively. The radium equivalent activities
      (Raeq) were in the range of 83-1574 Bq kg(-1). There was no appreciable radon
      exhalation, and the thoron surface exhalation rate varied from 942 to 7720 Bq m(
      2) h(-1). The annual effective dose was ranging from 0.05 to 0.81 mSv y(-1). Good
      correlation was observed between (232)Th content and thoron exhalation rate. The
      details of the study are presented in this article. 

PMID- 25977354
TI  - Detection of terrestrial radionuclides with X-ray fluorescence analysis.
AB  - This paper provides an overview of analytical methods frequently used to identify
      terrestrial radionuclides in samples. While radioactivity is normally measured
      through the ionising radiation produced during the spontaneous decay of unstable
      atoms, selected radionuclides or their chemical elements can be quantified with
      instrumental techniques based on stimulated emission or counting of atoms. The
      advantages and disadvantages of these analytical methods are discussed.
      Particular attention is paid to X-ray fluorescence analysis of materials
      containing uranium and thorium. It is also possible to determine the area
      distributions of these chemical elements in samples with the use of scanning X
      ray fluorescence systems. 

PMID- 25977355
TI  - The most recent international intercomparisons of radon and thoron monitors with
      the NIRS radon and thoron chambers.
AB  - The fifth international intercomparison for radon and fourth for thoron monitors
      were conducted at National Institute of Radiological Sciences (Japan) with the
      radon and thoron chambers. The tests were made under two different exposures to
      radon and two exposures (in two rounds due to limited space in the thoron
      chamber) to thoron. In these most recent intercomparisons, two new graphical
      methods recommended by the ISO standard, Mandel's h statistic and the Youden
      plot, were implemented to evaluate the consistency between laboratories and
      within laboratories.The presented data indicated that the performance quality of
      laboratories for radon measurement as expressed by the percentage difference
      parameter has been stable since the first international intercomparison for
      passive monitors carried out in 2007, and it amounted to around 50 for 10 % of
      the difference from the reference value. The thoron exercise showed that further
      development and additional studies to improve its measuring methods and
      reliability are needed. 

PMID- 25977356
TI  - Transvenous embolization of cavernous sinus dural arteriovenous fistula through a
      thrombosed inferior petrosal sinus utilizing 3D venography.
AB  - OBJECTIVE: We report a new technique in approaching the cavernous sinus through
      an occluded inferior petrosal sinus (IPS) using three-dimensional (3D)
      venography. CASE PRESENTATION: A patient diagnosed with arteriovenous fistula of
      the right cavernous sinus underwent transvenous embolization. The IPS was not
      detectable on angiogram. Retrograde injection of contrast with 3D imaging of the
      internal jugular vein clearly demonstrated the remnant of the IPS. By referring
      to the images obtained, catheterization of the cavernous sinus by way of the IPS
      was performed without difficulties. CONCLUSION: Three-dimensional venography for
      detecting the entrance to the IPS is a useful method and easy to perform. We
      believe that this technique should be considered whenever the access to an
      occluded IPS is necessary.

PMID- 25977357
TI  - Gene-environment interaction between the oxytocin receptor (OXTR) gene and
      parenting behaviour on children's theory of mind.
AB  - Theory of mind (ToM) is the ability to interpret and understand human behaviour
      by representing the mental states of others. Like many human capacities, ToM is
      thought to develop through both complex biological and socialization mechanisms.
      However, no study has examined the joint effect of genetic and environmental
      influences on ToM. This study examined how variability in the oxytocin receptor
      gene (OXTR) and parenting behavior--two widely studied factors in ToM development
      interacted to predict ToM in pre-school-aged children. Participants were 301
      children who were part of an ongoing longitudinal birth cohort study. ToM was
      assessed at age 4.5 using a previously validated scale. Parenting was assessed
      through observations of mothers' cognitively sensitive behaviours. Using a family
      based association design, it was suggestive that a particular variant
      (rs11131149) interacted with maternal cognitive sensitivity on children's ToM (P
      = 0.019). More copies of the major allele were associated with higher ToM as a
      function of increasing cognitive sensitivity. A sizeable 26% of the variability
      in ToM was accounted for by this interaction. This study provides the first
      empirical evidence of gene-environment interactions on ToM, supporting the notion
      that genetic factors may be modulated by potent environmental influences early in
      development.

PMID- 25977358
TI  - Type 1 innate lymphoid cells contribute to the pathogenesis of chronic hepatitis
      B.
AB  - Innate lymphoid cells (ILCs) function in producing effector cytokines in response
      to pathogenic infections. However, the roles and related mechanisms of the ILC
      subpopulations, ILC1 and ILC2, which mirror Th1 and Th2 in adaptive immunity,
      remain unclear. In this study, we found the markedly elevated levels of the ILC1
      transcription factor T-bet, the effector cytokine IFN-gamma and the IL/receptor
      signaling molecules IL-12/IL-12R, which are indispensable for ILC1
      differentiation, in the helper ILCs of chronic hepatitis B (CHB) patients. The
      elevated level of the ILC1 population was significantly associated with hepatic
      damage in CHB patients, and was not related to telbivudine treatment. In
      contrast, although we also observed elevated levels of ILC2-related factors,
      including IL-33, ST2, GATA3 and IL-13 in helper ILCs, the extent of elevation
      shown by each was lower than that shown by the ILC1-related factors. Furthermore,
      the activity of the ILC2s did not correlate with either HBV copies or liver
      damage. The findings of this study suggest potential pro-inflammatory roles for
      ILC1s in CHB pathogenesis, potentiating these cells and their related molecules
      as targets of diagnostic, prognostic and/or therapeutic strategies for hepatitis
      B. 

PMID- 25977359
TI  - Relationship between dysfunctional attitudes and childhood traumas in women with
      depression.
AB  - AIM: Psychological traumas in childhood could lead to dysfunctional attitudes
      causing negative cognitive structuring and mistakes in data processing. In this
      study, we aimed to research the relation of childhood traumas with dysfunctional
      attitudes in female patients with depressive disorder. METHOD: Seventy female
      patients diagnosed with depressive disorder and 50 healthy volunteers
      participated in the study, and the participants were administered a socio
      demographic form, the Beck Depression Inventory (BDI), the Childhood Trauma
      Questionnaire (CTQ) and the Dysfunctional Attitudes Scale (DAS). RESULTS:
      Comparing the two groups by median values of CTQ, total CTQ, sexual abuse,
      physical abuse, emotional abuse, physical neglect and emotional neglect, median
      values of the patient group were significantly higher compared to the control
      group, and comparison by median values of DAS revealed that median values of the
      patient group was significantly lower compared to the control group. In the
      correlation analysis carried out for finding the relation between CTQ and DAS,
      there was a significant negative correlation between DAS score and emotional
      abuse score. In the patient group, all kinds of abuses and neglects except for
      sexual abuse were at a higher rate in those with a history of depression in the
      family. CONCLUSION: In our study, a negative correlation was determined between
      DAS and only emotional abuse leading us to the finding that one of the factors
      mediating childhood traumas to cause depression could lead to dysfunctional
      attitudes.

PMID- 25977360
TI  - The ONCOTYROL Prostate Cancer Outcome and Policy Model: Effect of Prevalence
      Assumptions on the Benefit-Harm Balance of Screening.
AB  - BACKGROUND: The ONCOTYROL Prostate Cancer Outcome and Policy (PCOP) model is a
      state-transition microsimulation model evaluating the benefits and harms of
      prostate cancer (PCa) screening. The natural history and detection component of
      the original model was based on the 2003 version of the Erasmus MIcrosimulation
      SCreening ANalysis (MISCAN) model, which was not calibrated to prevalence data.
      Compared with data from autopsy studies, prevalence of latent PCa assumed by the
      original model is low, which may bias the model toward screening. Our objective
      was to recalibrate the original model to match prevalence data from autopsy
      studies as well and compare benefit-harm predictions of the 2 model versions
      differing in prevalence. METHODS: For recalibration, we reprogrammed the natural
      history and detection component of the PCOP model as a deterministic Markov state
      transition cohort model in the statistical software package R. All parameters
      were implemented as variables or time-dependent functions and calibrated
      simultaneously in a single run. Observed data used as calibration targets
      included data from autopsy studies, cancer registries, and the European
      Randomized Study of Screening for Prostate Cancer. Compared models were identical
      except for calibrated parameters. RESULTS: We calibrated 46 parameters.
      Prevalence from autopsy studies could not be fitted using the original parameter
      set. Additional parameters, allowing for interruption of disease progression and
      age-dependent screening sensitivities, were needed. Recalibration to higher
      prevalence demonstrated a considerable increase of overdiagnosis and decline of
      screening sensitivity, which significantly worsened the benefit-harm balance of
      screening. CONCLUSIONS: Our calibration suggests that not all cancers are at risk
      of progression, and screening sensitivity may be lower at older ages. PCa
      screening models that use calibration to simulate disease progression in the
      unobservable latent phase are highly sensitive to prevalence assumptions.

PMID- 25977361
TI  - Are There Scenarios When the Use of Non-Placebo-Control Groups in Experimental
      Trial Designs Increase Expected Value to Society?
AB  - BACKGROUND: Despite the benefits of the placebo-controlled trial design, it is
      limited by its inability to quantify total benefits and harms. Such trials, for
      example, are not designed to detect an intervention's placebo or nocebo effects,
      which if detected could alter the benefit-to-harm balance and change a decision
      to adopt or reject an intervention. OBJECTIVE: In this article, we explore
      scenarios in which alternative experimental trial designs, which differ in the
      type of control used, influence expected value across a range of pretest
      assumptions and study sample sizes. METHOD: We developed a decision model to
      compare 3 trial designs and their implications for decision making: 2-arm placebo
      controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial
      ("null-control"), and an innovative 3-arm trial design: intervention v. do
      nothing v. placebo trial ("novel design"). Four scenarios were explored regarding
      particular attributes of a hypothetical intervention: 1) all benefits and no
      harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious
      harm (no biological benefit or nocebo effect). RESULTS: Scenario 1: When sample
      sizes were very small, the null-control was preferred, but as sample sizes
      increased, expected value of all 3 designs converged. Scenario 2: The null
      control was preferred regardless of sample size when the ratio of placebo to
      nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3:
      When sample size was very small, the placebo-control was preferred when benefits
      outweighed harms, but the novel design was preferred when harms outweighed
      benefits. Scenario 4: The placebo-control was preferred when harms outweighed
      placebo benefits; otherwise, preference went to the null-control. LIMITATIONS:
      Scenarios are hypothetical, study designs have not been tested in a real-world
      setting, blinding is not possible in all designs, and some may argue the novel
      design poses ethical concerns. CONCLUSIONS: We identified scenarios in which
      alternative experimental study designs would confer greater expected value than
      the placebo-controlled trial design. The likelihood and prevalence of such
      situations warrant further study.

PMID- 25977362
TI  - A Simulation Modeling Framework to Optimize Programs Using Financial Incentives
      to Motivate Health Behavior Change.
AB  - INTRODUCTION: While increasingly popular among mid- to large-size employers,
      using financial incentives to induce health behavior change among employees has
      been controversial, in part due to poor quality and generalizability of studies
      to date. Thus, fundamental questions have been left unanswered: To generate
      positive economic returns on investment, what level of incentive should be
      offered for any given type of incentive program and among which employees?
      METHODS: We constructed a novel modeling framework that systematically identifies
      how to optimize marginal return on investment from programs incentivizing
      behavior change by integrating commonly collected data on health behaviors and
      associated costs. We integrated "demand curves" capturing individual differences
      in response to any given incentive with employee demographic and risk factor
      data. We also estimated the degree of self-selection that could be tolerated:
      that is, the maximum percentage of already-healthy employees who could enroll in
      a wellness program while still maintaining positive absolute return on
      investment. In a demonstration analysis, the modeling framework was applied to
      data from 3000 worksite physical activity programs across the nation. RESULTS:
      For physical activity programs, the incentive levels that would optimize marginal
      return on investment ($367/employee/year) were higher than average incentive
      levels currently offered ($143/employee/year). Yet a high degree of self
      selection could undermine the economic benefits of the program; if more than 17%
      of participants came from the top 10% of the physical activity distribution, the
      cost of the program would be expected to always be greater than its benefits.
      DISCUSSION: Our generalizable framework integrates individual differences in
      behavior and risk to systematically estimate the incentive level that optimizes
      marginal return on investment.

PMID- 25977363
TI  - Context-specific function of the LIM homeobox 1 transcription factor in head
      formation of the mouse embryo.
AB  - Lhx1 encodes a LIM homeobox transcription factor that is expressed in the
      primitive streak, mesoderm and anterior mesendoderm of the mouse embryo. Using a
      conditional Lhx1 flox mutation and three different Cre deleters, we demonstrated
      that LHX1 is required in the anterior mesendoderm, but not in the mesoderm, for
      formation of the head. LHX1 enables the morphogenetic movement of cells that
      accompanies the formation of the anterior mesendoderm, in part through regulation
      of Pcdh7 expression. LHX1 also regulates, in the anterior mesendoderm, the
      transcription of genes encoding negative regulators of WNT signalling, such as
      Dkk1, Hesx1, Cer1 and Gsc. Embryos carrying mutations in Pcdh7, generated using
      CRISPR-Cas9 technology, and embryos without Lhx1 function specifically in the
      anterior mesendoderm displayed head defects that partially phenocopied the
      truncation defects of Lhx1-null mutants. Therefore, disruption of Lhx1-dependent
      movement of the anterior mesendoderm cells and failure to modulate WNT signalling
      both resulted in the truncation of head structures. Compound mutants of Lhx1,
      Dkk1 and Ctnnb1 show an enhanced head truncation phenotype, pointing to a
      functional link between LHX1 transcriptional activity and the regulation of WNT
      signalling. Collectively, these results provide comprehensive insight into the
      context-specific function of LHX1 in head formation: LHX1 enables the formation
      of the anterior mesendoderm that is instrumental for mediating the inductive
      interaction with the anterior neuroectoderm and LHX1 also regulates the
      expression of factors in the signalling cascade that modulate the level of WNT
      activity. 

PMID- 25977364
TI  - Neural crest migration is driven by a few trailblazer cells with a unique
      molecular signature narrowly confined to the invasive front.
AB  - Neural crest (NC) cell migration is crucial to the formation of peripheral
      tissues during vertebrate development. However, how NC cells respond to different
      microenvironments to maintain persistence of direction and cohesion in
      multicellular streams remains unclear. To address this, we profiled eight
      subregions of a typical cranial NC cell migratory stream. Hierarchical clustering
      showed significant differences in the expression profiles of the lead three
      subregions compared with newly emerged cells. Multiplexed imaging of mRNA
      expression using fluorescent hybridization chain reaction (HCR) quantitatively
      confirmed the expression profiles of lead cells. Computational modeling predicted
      that a small fraction of lead cells that detect directional information is
      optimal for successful stream migration. Single-cell profiling then revealed a
      unique molecular signature that is consistent and stable over time in a subset of
      lead cells within the most advanced portion of the migratory front, which we term
      trailblazers. Model simulations that forced a lead cell behavior in the trailing
      subpopulation predicted cell bunching near the migratory domain entrance.
      Misexpression of the trailblazer molecular signature by perturbation of two
      upstream transcription factors agreed with the in silico prediction and showed
      alterations to NC cell migration distance and stream shape. These data are the
      first to characterize the molecular diversity within an NC cell migratory stream
      and offer insights into how molecular patterns are transduced into cell
      behaviors. 

PMID- 25977365
TI  - The Hippo pathway effector Yki downregulates Wg signaling to promote retinal
      differentiation in the Drosophila eye.
AB  - The evolutionarily conserved Hippo signaling pathway is known to regulate cell
      proliferation and maintain tissue homeostasis during development. We found that
      activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes
      separable effects on growth and differentiation of the Drosophila eye. We present
      evidence supporting a role for Yki in suppressing eye fate by downregulation of
      the core retinal determination genes. Other upstream regulators of the Hippo
      pathway mediate this effect of Yki on retinal differentiation. Here, we show
      that, in the developing eye, Yki can prevent retinal differentiation by blocking
      morphogenetic furrow (MF) progression and R8 specification. The inhibition of MF
      progression is due to ectopic induction of Wingless (Wg) signaling and Homothorax
      (Hth), the negative regulators of eye development. Modulating Wg signaling can
      modify Yki-mediated suppression of eye fate. Furthermore, ectopic Hth induction
      due to Yki activation in the eye is dependent on Wg. Last, using Cut (Ct), a
      marker for the antennal fate, we show that suppression of eye fate by
      hyperactivation of yki does not change the cell fate (from eye to antenna
      specific fate). In summary, we provide the genetic mechanism by which yki plays a
      role in cell fate specification and differentiation - a novel aspect of Yki
      function that is emerging from multiple model organisms. 

PMID- 25977367
TI  - Compensatory branching morphogenesis of stalk cells in the Drosophila trachea.
AB  - Tubes are essential for nutrient transport and gas exchange in multicellular
      eukaryotes, but how connections between different tube types are maintained over
      time is unknown. In the Drosophila tracheal system, mutations in oak gall (okg)
      and conjoined (cnj) confer identical defects, including late onset blockage near
      the terminal cell-stalk cell junction and the ectopic extension of autocellular,
      seamed tubes into the terminal cell. We determined that okg and cnj encode the E
      and G subunits of the vacuolar ATPase (vATPase) and showed that both the V0 and
      V1 domains are required for terminal cell morphogenesis. Remarkably, the ectopic
      seamed tubes running along vATPase-deficient terminal cells belonged to the
      neighboring stalk cells. All vATPase-deficient tracheal cells had reduced apical
      domains and terminal cells displayed mislocalized apical proteins. Consistent
      with recent reports that the mTOR and vATPase pathways intersect, we found that
      mTOR pathway mutants phenocopied okg and cnj. Furthermore, terminal cells
      depleted for the apical determinants Par6 or aPKC had identical ectopic seamed
      tube defects. We thus identify a novel mechanism of compensatory branching in
      which stalk cells extend autocellular tubes into neighboring terminal cells with
      undersized apical domains. This compensatory branching also occurs in response to
      injury, with damaged terminal cells being rapidly invaded by their stalk cell
      neighbor. 

PMID- 25977366
TI  - Essential elements for translation: the germline factor Vasa functions broadly in
      somatic cells.
AB  - Vasa is a conserved RNA-helicase found in the germ lines of all metazoans tested.
      Whereas Vasa presence is often indicated as a metric for germline determination
      in animals, it is also expressed in stem cells of diverse origin. Recent research
      suggests, however, that Vasa has a much broader function, including a significant
      role in cell cycle regulation. Results herein indicate that Vasa is utilized
      widely, and often induced transiently, during development in diverse somatic
      cells and adult precursor tissues. We identified that Vasa in the sea urchin is
      essential for: (1) general mRNA translation during embryogenesis, (2)
      developmental re-programming upon manipulations to the embryo and (3) larval
      wound healing. We also learned that Vasa interacted with mRNAs in the perinuclear
      area and at the spindle in an Importin-dependent manner during cell cycle
      progression. These results suggest that, when present, Vasa functions are
      essential to contributing to developmental regulation. 

PMID- 25977368
TI  - Inhibition of Daughterless by Extramacrochaetae mediates Notch-induced cell
      proliferation.
AB  - During development, the rate of cell proliferation must be constantly monitored
      so that an individual tissue achieves its correct size. Mutations in genes that
      normally promote tissue growth often result in undersized, disorganized and non
      functional organs. However, mutations in genes that encode growth inhibitors can
      trigger the onset of tumorigenesis and cancer. The developing eye of the fruit
      fly, Drosophila melanogaster, has become a premier model system for studies that
      are focused on identifying the molecular mechanisms that underpin growth control.
      Here, we examine the mechanism by which the Notch pathway, a major contributor to
      growth, promotes cell proliferation in the developing eye. Current models propose
      that the Notch pathway directly influences cell proliferation by regulating
      growth-promoting genes such as four-jointed, cyclin D1 and E2f1. Here, we show
      that, in addition to these mechanisms, some Notch signaling is devoted to
      blocking the growth-suppressing activity of the bHLH DNA-binding protein
      Daughterless (Da). We demonstrate that Notch signaling activates the expression
      of extramacrochaetae (emc), which encodes a helix-loop-helix (HLH) transcription
      factor. Emc, in turn, then forms a biochemical complex with Da. As Emc lacks a
      basic DNA-binding domain, the Emc-Da heterodimer cannot bind to and regulate
      genomic targets. One effect of Da sequestration is to relieve the repression on
      growth. Here, we present data supporting our model that Notch-induced cell
      proliferation in the developing eye is mediated in part by the activity of Emc. 

PMID- 25977369
TI  - Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone
      development.
AB  - Vascular endothelial growth factor A (Vegfa) has important roles in endochondral
      bone formation. Osteoblast precursors, endothelial cells and osteoclasts migrate
      from perichondrium into primary ossification centers of cartilage templates of
      future bones in response to Vegfa secreted by (pre)hypertrophic chondrocytes.
      Perichondrial osteolineage cells also produce Vegfa, but its function is not well
      understood. By deleting Vegfa in osteolineage cells in vivo, we demonstrate that
      progenitor-derived Vegfa is required for blood vessel recruitment in
      perichondrium and the differentiation of osteoblast precursors in mice.
      Conditional deletion of Vegfa receptors indicates that Vegfa-dependent effects on
      osteoblast differentiation are mediated by Vegf receptor 2 (Vegfr2). In addition,
      Vegfa/Vegfr2 signaling stimulates the expression and activity of Indian hedgehog,
      increases the expression of beta-catenin and inhibits Notch2. Our findings
      identify Vegfa as a regulator of perichondrial vascularity and osteoblast
      differentiation at early stages of bone development. 

PMID- 25977370
TI  - Cancer. The transcription factor GABP selectively binds and activates the mutant
      TERT promoter in cancer.
AB  - Reactivation of telomerase reverse transcriptase (TERT) expression enables cells
      to overcome replicative senescence and escape apoptosis, which are fundamental
      steps in the initiation of human cancer. Multiple cancer types, including up to
      83% of glioblastomas (GBMs), harbor highly recurrent TERT promoter mutations of
      unknown function but specific to two nucleotide positions. We identified the
      functional consequence of these mutations in GBMs to be recruitment of the
      multimeric GA-binding protein (GABP) transcription factor specifically to the
      mutant promoter. Allelic recruitment of GABP is consistently observed across four
      cancer types, highlighting a shared mechanism underlying TERT reactivation.
      Tandem flanking native E26 transformation-specific motifs critically cooperate
      with these mutations to activate TERT, probably by facilitating GABP
      heterotetramer binding. GABP thus directly links TERT promoter mutations to
      aberrant expression in multiple cancers. 

PMID- 25977372
TI  - Friction. Macroscale superlubricity enabled by graphene nanoscroll formation.
AB  - Friction and wear remain as the primary modes of mechanical energy dissipation in
      moving mechanical assemblies; thus, it is desirable to minimize friction in a
      number of applications. We demonstrate that superlubricity can be realized at
      engineering scale when graphene is used in combination with nanodiamond particles
      and diamondlike carbon (DLC). Macroscopic superlubricity originates because
      graphene patches at a sliding interface wrap around nanodiamonds to form
      nanoscrolls with reduced contact area that slide against the DLC surface,
      achieving an incommensurate contact and substantially reduced coefficient of
      friction (~0.004). Atomistic simulations elucidate the overall mechanism and
      mesoscopic link bridging the nanoscale mechanics and macroscopic experimental
      observations. 

PMID- 25977371
TI  - Social evolution. Genomic signatures of evolutionary transitions from solitary to
      group living.
AB  - The evolution of eusociality is one of the major transitions in evolution, but
      the underlying genomic changes are unknown. We compared the genomes of 10 bee
      species that vary in social complexity, representing multiple independent
      transitions in social evolution, and report three major findings. First, many
      important genes show evidence of neutral evolution as a consequence of relaxed
      selection with increasing social complexity. Second, there is no single road map
      to eusociality; independent evolutionary transitions in sociality have
      independent genetic underpinnings. Third, though clearly independent in detail,
      these transitions do have similar general features, including an increase in
      constrained protein evolution accompanied by increases in the potential for gene
      regulation and decreases in diversity and abundance of transposable elements.
      Eusociality may arise through different mechanisms each time, but would likely
      always involve an increase in the complexity of gene networks. 

PMID- 25977373
TI  - Neurodegeneration. C9ORF72 repeat expansions in mice cause TDP-43 pathology,
      neuronal loss, and behavioral deficits.
AB  - The major genetic cause of frontotemporal dementia and amyotrophic lateral
      sclerosis is a G4C2 repeat expansion in C9ORF72. Efforts to combat
      neurodegeneration associated with "c9FTD/ALS" are hindered by a lack of animal
      models recapitulating disease features. We developed a mouse model to mimic both
      neuropathological and clinical c9FTD/ALS phenotypes. We expressed (G4C2)66
      throughout the murine central nervous system by means of somatic brain
      transgenesis mediated by adeno-associated virus. Brains of 6-month-old mice
      contained nuclear RNA foci, inclusions of poly(Gly-Pro), poly(Gly-Ala), and
      poly(Gly-Arg) dipeptide repeat proteins, as well as TDP-43 pathology. These mouse
      brains also exhibited cortical neuron and cerebellar Purkinje cell loss,
      astrogliosis, and decreased weight. (G4C2)66 mice also developed behavioral
      abnormalities similar to clinical symptoms of c9FTD/ALS patients, including
      hyperactivity, anxiety, antisocial behavior, and motor deficits. 

PMID- 25977374
TI  - Factors affecting faecal immunochemical test positive rates: demographic,
      pathological, behavioural and environmental variables.
AB  - OBJECTIVES: Positive rates in faecal immunochemical test (FIT)-based colorectal
      cancer screening programmes vary, suggesting that differences between programmes
      may affect test results. We examined whether demographic, pathological,
      behavioural, and environmental factors affected haemoglobin concentration and
      positive rates where samples are mailed. METHODS: A retrospective cohort study;
      34,298 collection devices were sent, over five years, to screening invitees
      (median age 60.6). Participant demographics, temperature on sample postage day,
      and previous screening were recorded. Outcomes from colonoscopy performed within
      a year following FIT were collected. Multivariate logistic regression identified
      significant predictors of test positivity. RESULTS: Higher positive rate was
      independently associated with male gender, older age, lower socioeconomic status,
      and distally located neoplasia, and negatively associated with previous screening
      (p < 0.05). Older males had higher faecal haemoglobin concentrations and were
      less likely to have a false positive result at colonoscopy (p < 0.05). High
      temperature on the sample postage day was associated with reduced haemoglobin
      concentration and positivity rate (26-35C: Odds ratio 0.78, 95% confidence
      interval 0.66-0.93), but was not associated with missed significant neoplasia at
      colonoscopy (p > 0.05). CONCLUSIONS: Haemoglobin concentrations, and therefore
      FIT positivity, were affected by factors that vary between screening programmes.
      Participant demographics and high temperature at postage had significant effects.
      The impact of temperature could be reduced by seasonal scheduling of invitations.
      The importance of screening, and following up positive test results, particularly
      in older males, should be promoted.

PMID- 25977375
TI  - Exploring the trend of increased cervical intraepithelial neoplasia detection
      rates in the Netherlands.
AB  - OBJECTIVE: Over the last decade, cervical intraepithelial neoplasia (CIN)
      detection has increased in the Netherlands. We investigated the underlying
      mechanism by quantifying the increase, and analyzing patterns of CIN and cervical
      cancer detection over time. METHODS: We observed annual CIN and cervical cancer
      detection rates (DRs) per 10,000 primary smears within the Dutch screening
      programme for 2000-2011. Joinpoint analyses were performed to determine changes
      in time trends, logistic regression analyses to assess the relative risk of
      calendar time on histological outcomes, adjusted for demographic factors and type
      of primary cytology test used. RESULTS: Trends of increased detection occurred
      for all CIN grades (ie. DRs increased from 17.8 to 36.1, from 21.0 to 35.5, and
      from 43.4 to 64.6 for CIN I, II, and III from 2003 to 2009). After adjusting for
      demographic factors, DRs were still 2.11 (95% confidence interval (CI): 1.95,
      2.29), 1.79 (95% CI: 1.66, 1.92) and 1.59 (95% CI: 1.50, 1.67) times larger in
      2009. When also adjusting for the type of cytology test, DRs were 1.90 (95% CI:
      1.62, 2.22), 1.48 (95% CI: 1.22, 1.79) and 1.55 (95% CI: 1.39, 1.73) times
      larger. No trends in cervical cancer DRs were found. CONCLUSIONS: The
      implementation of liquid-based cytology contributed to the CIN increase. If some
      of these extra detected CIN are regressive this leads to overdiagnosis. Other
      factors, such as an increased cervical cancer risk, and implementation of imaging
      assisted reading, could also have contributed.

PMID- 25977376
TI  - Vasculogenic mimicry: lessons from melanocytic tumors.
AB  - Tumor cell vasculogenic mimicry refers to the formation of tumor cell-lined
      vessels that contribute to tumor neovascularization and nutrient and oxygen
      supply. These tumor cells express many endothelial and stem cell markers,
      resulting in them having a unique phenotype. This phenomenon is observed in a
      variety of neoplasms, such as glioblastomas and sarcomas, as well as breast,
      ovarian, liver and lung carcinomas. It is also evident in melanocytic lesions,
      regardless of their benign or malignant nature. The biochemical and molecular
      events that regulate vasculogenic mimicry provide opportunities for development
      of novel forms of tumor-targeted treatments. Furthermore, the presence of this
      process in a tumor might have prognostic implications. 

PMID- 25977377
TI  - Enrichment and Schwann Cell Differentiation of Neural Crest-derived Dental Pulp
      Stem Cells.
AB  - BACKGROUND/AIM: As already described in previous studies, neural crest stem cells
      (NCSCs) can be found in adult human dental pulp. The present study investigated
      the methodology for enrichment and differentiation-induction of the above
      mentioned cells. MATERIALS AND METHODS: Dental pulp was extracted from human
      wisdom teeth of four patients and subsequently cultured as explants on
      fibronectin-coated plates in neurobasal medium supplemented with B27, basic
      fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin, l
      glutamine and neuregulin-beta1. The cells were then characterized by
      immunofluorescence, while their differentiation-potential was tested by the
      attempt to induce cells into different lineages, i.e. osteogenic, melanocytic and
      glial. RESULTS: The enriched cell population expressed nestin, CD271 and SOX10,
      which are well-known markers for NCSCs. Consequently, the cells were successfully
      induced to differentiate into osteoblasts, melanocytes and Schwann cells,
      expressing the corresponding differentiation markers. CONCLUSION: Human adult
      dental pulp contains a population of stem cells with neural crest ontogeny, which
      can thus be recruited for multiple regenerative therapies.

PMID- 25977378
TI  - Monoclonal antibody against transforming growth factor Beta 1 does not influence
      liver regeneration after resection in large animal experiments.
AB  - BACKGROUND: Steatohepatitis is a type of histopathological liver injury that can
      be caused by chemotherapy [chemotherapy-associated steatohepatitis (CASH)] and
      can progress to liver fibrosis or cirrhosis. CASH impairs liver functions,
      including liver regeneration. Impaired liver regeneration reduces the number of
      patients who can undergo liver resection and reduces opportunities for curative
      therapies. Transforming growth factor-beta (TGFbeta) is a potent mitotic
      inhibitor that participates during the last phase of liver regeneration. TGFbeta
      has been studied as a potential solution to the development of liver fibrosis or
      hepatocellular carcinoma. AIM: The first aim of our study was to establish a
      large animal model of toxic liver injury and test the ability of a monoclonal
      antibody against TGFbeta (MAB-TGFbeta) to increase liver-regeneration capacity.
      The second aim was to evaluate the degree to which early preoperative
      administration of MAB-TGFbeta influenced hepatic parenchyma regeneration
      following healthy liver resection in a swine experimental model. MATERIALS AND
      METHODS: Toxic liver injury was induced by alcohol consumption and regular
      intraperitoneal administration of carbon tetrachloride (CCl4) to piglets for 10
      weeks. After 10 weeks, the piglets underwent liver resection of the left lateral
      and left medial liver lobes. Twenty-four hours after liver resection, MAB-TGFbeta
      was administered to the experimental group (10 piglets) and a physiological
      solution to the control group (10 piglets) through an implemented port-a-cath. In
      the second part of the study, either MAB-TGFbeta or a saline solution control
      were administered at 12 and 4 days prior to resection of the right lobes of
      healthy liver (six experimental and 10 control group subjects). Observation and
      follow-up was performed throughout the entire experiment. Ultrasound and
      biochemical tests (for albumin, cholinesterase, aspartate aminotransferase,
      alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase,
      bilirubin, urea, creatinine and ammonia levels) were performed on postoperative
      days 1, 3, 7, 10 and 14. A histopathological examination was performed after
      sacrificing the animals on the 14th postoperative day. RESULTS: No significant
      differences were observed between groups when using ultrasound volumetry to
      assess the regenerative volume of the liver in both experiments. The only
      significant differences found when comparing biochemical parameters between
      groups were higher serum levels of both creatinine and gamma-glutamyl transferase
      in the experimental group with preoperative administration of MAB-TGFbeta. There
      were no differences in the histological analyses of hepatic lobule cross
      sectional area nor in the proliferative index between animals receiving MAB
      TGFbeta and those treated with physiological saline solution before resection.
      Hepatocytic cross-sectional areas were larger in animals treated with
      physiological solution versus those treated with MAB-TGFbeta on the operative
      day; however, these values were comparable between groups by 14 days following
      resection. CONCLUSION: We established a large animal model of toxic liver injury
      that is comparable with CASH. The toxic injury that was induced without pause
      between administrations was probably more extensive than occurs in CASH, and
      there was no effect of MAB-TGFbeta administration on liver regeneration. MAB
      TGFbeta administration did not lead to any observable side-effects, indicating
      that it could be a promising solution for use as an oncologic-targeted treatment.

PMID- 25977379
TI  - The Radical Scavenging Activity and Cytotoxicity of Resveratrol, Orcinol and 4
      Allylphenol and their Inhibitory Effects on Cox-2 Gene Expression and Nf-kappab
      Activation in RAW264.7 Cells Stimulated with Porphyromonas gingivalis-fimbriae.
AB  - BACKGROUND/AIM: Resveratrol is a polyphenol with efficient anti-oxidative and
      anti-inflammatory activity. To clarify the molecular mechanism responsible for
      its anti-inflammatory action, we investigated the radical scavenging activity,
      cytotoxicity and anti-inflammatory activity of resveratrol and its related
      compounds, orcinol and 4-allylphenol. MATERIALS AND METHODS: The radical
      scavenging activities of these compounds were determined by the DPPH (2,2'
      diphenyl-1-picrylhydrazyl) assay and their cytotoxicities against RAW264.7 cells
      were determined using a cell-counting kit (CCK-8). The inhibitory effects of
      these compounds on cyclooxygenase-2 (Cox2) expression in RAW264.7 cells
      stimulated with Porphyromonas gingivalis (Pg) fimbriae were also determined using
      real-time polymerase chain reaction and western blot analysis, while inhibition
      of the fimbria-stimulated activation of nuclear factor-kappa B (Nf-kappab) was
      evaluated using western blot analysis and enzyme-linked immunosorbent assay-like
      microwell colorimetric transcription factor activity assay, respectively. The
      quantum chemical parameters were calculated on the basis of the density function
      theory (DFT) BLYP/6-31G*. RESULTS: DPPH radical scavenging activity declined in
      the order resveratrol > orcinol > 4-allylphenol. The cytotoxicity of the
      compounds was in the order 4-allylphenol > resveratrol > orcinol. The inhibitory
      effect on Pg fimbria-stimulated Cox2 expression and Nf-kappab activation was
      enhanced by resveratrol-alone. Resveratrol showed high electronegativity (chi)
      and softness (sigma) values, as determined by quantum chemical calculations.
      CONCLUSION: Resveratrol exerts potent anti-inflammatory activity in RAW264.7
      cells stimulated with Pg-fimbriae and may be applicable as a therapeutic agent
      for inflammatory periodontal disease as a manifestation of systemic disease.

PMID- 25977380
TI  - No Dynamic Changes in Blood-brain Barrier Permeability Occur in Developing Rats
      During Local Cortex Exposure to Microwaves.
AB  - Little information is available about the effects of exposure to radiofrequency
      electromagnetic fields (RF) on cerebral microcirculation during rat developmental
      stages. We investigated whether the permeability of the blood-brain barrier (BBB)
      in juvenile and young adult rats was modified during local cortex exposure to RF
      under non-thermal conditions. The cortex tissue targeted was locally exposed to
      1457 MHz RF at an average specific absorption rate of 2.0 W/kg in the target area
      for 50 min and permeability changes in the BBB of the pia mater were measured
      directly, using intravital fluorescence microscopy. There was no significant
      difference in extravasation of intravenously-injected dye between exposed and
      sham-exposed groups of either category of rats. No histological evidence of
      albumin leakage was found in any of the brains just after exposure, indicating
      that no traces of BBB disruption remained. These findings suggest that no dynamic
      changes occurred in BBB permeability of the rats at either of these developmental
      stages, even during local RF exposure at non-thermal levels. 

PMID- 25977381
TI  - beta-Glucan from Saccharomyces cerevisiae Induces IFN-gamma Production In Vivo in
      BALB/c Mice.
AB  - AIM: beta-Glucan is one of the most abundant polymers in nature and has been
      established as an immunomodulator. This compound has notable physiological
      effects on mammalian immune systems, including anti-tumor and anti-infective
      activities and can activate the immune response. It is considered that the immune
      stimulating activities of beta-glucan can depend on physicochemical parameters,
      such as molecular size. Saccharomyces cerevisiae, also known as baker's yeast, is
      a frequently used source of beta-glucan. The aim of the experiments was to
      investigate how different Saccharomyces cerevisiae beta-glucan preparations with
      different molecular size affect interferon-gamma (IFN-gamma) production in BALB/c
      mice. MATERIALS AND METHODS: In vivo and in vitro BALB/c mouse models were used
      for the investigations. Different beta-glucan preparations were orally
      administrated in the in vivo experiments. IFN-gamma production in BALB/c mice was
      analyzed by enzyme-linked immunosorbent assay and measuring interferon-gamma RNA
      concentration. RESULTS: The results showed that orally-administered beta-glucan
      from S. cerevisiae enhanced IFN-gamma production in BALB/c mice in the in vivo
      model, but not by mouse leukocytes in vitro. Moreover, water-soluble beta-glucan
      enhanced IFN-gamma production more effectively than did particulate beta-glucan.
      CONCLUSION: IFN-gamma plays an important role in immunity against viral and
      bacterial infections. Our experiments have shown that beta-glucan preparations
      enhance IFN-gamma production in BALB/c mice and can be potentially used for
      immune system stimulation in mammals. Current results may be used to develop
      soluble beta-glucan nutritional supplements.

PMID- 25977382
TI  - Massage may initiate tendon structural changes--a preliminary study.
AB  - BACKGROUND: Physical exercise is now a widely known and studied factor of the
      proper functioning of living organisms. Many questions remain unanswered
      concerning various aspects of the changes in the morphology of structures
      subjected to chronic physical exercise. MATERIALS AND METHODS: This study was
      conducted on fifty Buffalo strain rats, randomly divided into two equal
      (experimental and control) groups. All animals were subjected to physical
      training on a running track for 10 weeks, whereas only in the experimental group,
      massage was additionally applied five-times per week. RESULTS: An increase in the
      percentage of collagen fibers in tendons with the smallest diameter (<=100 nm)
      was observed only in the experimental group in week 3, followed by a decrease in
      weeks 5 and 7. A subsequent repeated increase was observed in week 10 of the
      study. No significant differences were observed for either study group in the
      number of collagen fibers based on fiber diameter (101-200 nm, 201-300 nm and 301
      400 nm). CONCLUSION: The results of this preliminary study showed that long-term
      massage performed during running training may initiate for small structural
      changes in the rat tendon. Further morphological studies with prolonged
      observation periods are recommended.

PMID- 25977383
TI  - The Effect of GHR/exon-3 Polymorphism and Serum GH, IGF-1 and IGFBP-3 Levels in
      Diabetes and Coronary Heart Disease.
AB  - AIM: The present study investigated the effects of growth hormone (GH), insulin
      like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP
      3) and GH-receptor (GHR)/exon-3 polymorphism on diabetes mellitus (DM) and
      coronary heart disease (CHD) patients. PATIENTS AND METHODS: Ninety patients with
      CHD, 90 patients with DM and 96 controls were included in this study. The GH, IGF
      1 and IGFBP-3 serum levels were measured with enzyme-linked immunosorbent assay.
      GHR/exon-3 variants were determined by multiplex-polymerase chain reaction.
      RESULTS: The frequency of all alleles and genotypes in all study groups were
      distributed according to the Hardy-Weinberg equilibrium. In addition, any
      association between GHR/exon-3 variants and the presence of risk factors were
      detected. The blood levels of GH, IGF-1 and IGFBP-3 were not distributed
      according to GHR/exon-3 variants. However, in the DM group, higher levels of IGF
      1 and lower levels of GH and IGFBP-3, and in CHD group lower levels of IGF-1, GH
      and IGFBP-3 were observed. The order of GH levels were DM<CHD< Controls; IGF-1
      levels were CHD<Controls<DM and IGFBP-3 levels were CHD<DM<Controls. CONCLUSION:
      No direct effect of GHR/exon-3 polymorphism was observed in DM or CHD patients.
      However GH, IGF-1, IGFBP-3 and insulin were thought to act together to establish
      body homeostasis in patients with DM and CHD.

PMID- 25977384
TI  - Protective Effects of Pyridoxamine Against UVC-induced Programmed Cell Death in
      HaCaT Cells.
AB  - BACKGROUND: Exposure to ultraviolet (UV) light is closely related to human
      diseases, such as skin cancer, due to irreversible injuries to the skin cells.
      The UV-induced DNA damage and programmed cell death are important determinants
      for skin carcinogenesis. The aim of the present study was to investigate the anti
      ultraviolet-C (UVC) effects of pyridoxamine in human keratinocyte HaCaT cells and
      its mechanisms of action. RESULTS: UVC-induced programmed cell death in HaCaT
      cells was abrogated by treated the cells immediately after UVC irradiation with
      40, 80 and 160 MUM of pyridoxamine. Monitoring the UVC-induced-specific reactive
      oxygen species, we found that 20, 40, 80 and 160 MUM of pyridoxamine was also
      effective in suppressing the induction of reactive oxygen species by UVC.
      CONCLUSION: Overall, our results provided evidence showing that pyridoxamine was
      effective in protecting HaCaT cells from UVC-induced programmed cell death and
      may be a potential anti-UVC agent in life and clinical practice.

PMID- 25977385
TI  - Utility of retinal thickness analyzer in early diagnosis of glaucomatous damage.
AB  - AIM: The utility of retinal thickness analysis (RTA) in the primary open-angle
      glaucoma (POAG) early diagnosis and in the follow-up was evaluated. MATERIALS AND
      METHODS: The nerve fibre layer thickness was analysed with the RTA by repeated
      examinations in POAG, ocular hypertension (OH) and healthy subjects (H). RESULTS:
      In the POAG group, a statistically significant reduction of mean retinal
      thickness (MRT) compared to the H group was evidenced both in the total area
      examined and in each of the four quadrants. The visual field evaluation
      classified the POAG group's visual fields in stage 1 and the OH group's visual
      fields in stage 0. CONCLUSION: RTA reveals a variation of mean retinal thickness,
      even before a functional and/or morphological optic nerve alteration appears. RTA
      is a complementary tool with the exams usually applied in the diagnosis of
      glaucoma, even though the information obtained is not specific for glaucoma.

PMID- 25977386
TI  - Maspin highlights colorectal serrated polyps: preliminary findings.
AB  - AIMS: Maspin, a 42-kDa serine proteinase inhibitor, is a tumor suppressor protein
      that stimulates apoptosis and inhibits motility, invasion and cancer metastasis.
      Mutant maspin leads to partial loss of tumor suppressor function, decreased
      susceptibility to apoptosis and to malignant progression. We recently found
      maspin expression (ME) in the cytoplasm of serrated colonic lesions, such as
      hyperplastic polyps (HP) and sessile serrated adenoma/polyps (SSA/P). MATERIALS
      AND METHODS: ME was investigated in 10 colorectal lesions: three HP, three SSA/P
      and four conventional colorectal adenomas (CCRA). RESULTS: Widespread cytoplasmic
      ME (comprising the entire height and width of the lesion) was present in the
      three HP and in the three SSA/P. In contrast, ME was only focally expressed in
      the four CCRA. ME was not present in the normal mucosa adjacent to those lesions.
      CONCLUSION: These preliminary findings suggest that maspin might be of help in
      discriminating between serrated colonic lesions (HP and SSA/P) and CCRA.

PMID- 25977387
TI  - Cerebrovascular Aneurysms May Be Associated with Thrombophilia-predisposing
      Mutations in Patients with Familial Risk.
AB  - BACKGROUND: Pathogenesis of cerebral aneurysms implicates several risk factors.
      Three common thrombophilia-predisposing mutations were studied in patients with
      cerebrovascular aneurysms. PATIENTS AND METHODS: A total of 186 Greeks (66
      patients with intracranial aneurysm and 120 healthy controls) were studied.
      Fifteen patients had a family history of thrombophilia, while two of them had a
      first-degree relative with an aneurysm. Genetic analysis for thrombophilia
      predisposing mutations factor V Leiden, factor II (prothrombin) G20210A and
      methylenetetrahydrofolate reductase C677T was performed in all subjects. RESULTS:
      Genotypic distributions and allelic frequencies were compatible with the Hardy
      Weinberg equilibrium. There was no significant difference between healthy
      individuals and patients in mutant allelic frequencies of thrombophilia
      mutations. Nevertheless, the mutant allelic frequencies of factor V and II
      mutations were significantly increased in the sub-group of patients with a
      positive family history of thrombophilia compared to controls (p<=0.003).
      CONCLUSION: Certain thrombophilia-related mutations may contribute to
      pathogenesis of intracranial aneurysms in a subset of the general population.

PMID- 25977388
TI  - Low vitamin D levels are associated with the presence of serum cryoglobulins in
      patients with chronic HCV infection.
AB  - BACKGROUND/AIM: Mixed Cryoglobulinemia (MC) represents the most frequent
      extrahepatic manifestation of chronic Hepatitis C Virus (HCV) infection. Its
      pathogenic mechanisms involve HCV-induced chronic stimulation of B-lymphocytes.
      We aimed to investigate the relationship between serum levels of vitamin D (a
      regulator of immune response) and the presence of serum cryoglobulins in the
      setting of HCV infection. PATIENTS AND METHODS: We evaluated the serum
      concentration of 25(OH)vitamin D and cryoglobulins in 106 patients with chronic
      HCV infection. RESULTS: Thirty patients (28.3%) showed the presence of serum
      cryoglobulins. For the cohort overall, the median serum 25(OH)vitamin D level was
      10.95 ng/ml. Patients with serum cryoglobulins had significantly lower levels of
      25(OH)vitamin D (5.61 ng/ml) than those without (13.65 ng/ml, p=0.029). At
      multivariate analysis, severe hypovitaminosis [i.e. 25(OH)vitamin D <13 ng/ml]
      was the only independent predictor of cryoglobulinemia (odds ratio=3.108).
      CONCLUSION: Severe deficiency of vitamin D was independently associated with
      mixed cryoglobulinemia in patients with HCV infection.

PMID- 25977389
TI  - Polydatin administration improves serum biochemical parameters and oxidative
      stress markers during chronic alcoholism: a pilot study.
AB  - AIM: Polydatin, a hydroxystilbene derived from the rhizome of Polygonum
      cuspidatum, elicits hepatoprotective and neuroprotective effects through its anti
      oxidant properties. The present study aimed to determine the effects of oral
      administration of polydatin in alcoholic patients in order to improve liver
      biochemical parameters, serum oxidative stress and mental state. We enrolled 20
      chronic alcoholic patients hospitalized for rehabilitative therapy. The patients
      were divided into two groups receiving the following treatment regimes for two
      weeks: administration of an anti-oxidant nutritional supplement containing
      glutathione and vitamin C (group 1), or glutathione, vitamin C and polydatin
      (group 2). RESULTS: The results of the present study show that elevated plasma
      aspartate aminotransferase and alanine aminotransferase levels in patients after
      two weeks of alcohol withdrawal were significantly reduced by polydatin (group
      2), when compared to group 1. Polydatin also significantly reduced lipid
      peroxidation levels. Finally, our preliminary data resulting from the analysis of
      the Mini-Mental Status suggest that polydatin improves cognitive performance.
      CONCLUSION: Daily dietary administration of polydatin should be considered for
      prevention and treatment of liver disease and cognitive impairment in alcoholic
      patients.

PMID- 25977391
TI  - Year in review 2014: basic science and epidemiology.

PMID- 25977390
TI  - Seasonal variation of serum vitamin D among Greek female patients with
      osteoporosis.
AB  - BACKGROUND/AIM: Vitamin D (vitD) levels are positively associated with bone
      health and seasonality affects serum vit D. The aim of the study was to
      investigate the degree of seasonal variation on 25-hydroxyvitamin D (25(OH)D)
      serum levels in a population-based cohort of post-menopausal women with
      osteoporosis. PATIENTS AND METHODS: Serum levels of 25(OH)D were assessed in 596
      patients (mean age=65.3 years; standard deviation (SD)=9.4) in different time
      points over a period of 2.5 years. RESULTS: The minimum 25(OH)D serum levels were
      observed in March (13.4+/-9.5 ng/ml) and the maximum levels in August, September
      and October (29.1+/-16.1, 28.9+/-12 and 28.4+/-8.9 ng/ml, respectively). The
      prevalence of vitD deficiency, insufficiency and sufficiency in March was 76.5,
      15.7 and 7.8%, respectively. On the contrary, the highest prevalence of vitD
      sufficiency was observed in August, September and October (38.1%, 45.3% and
      46.5%, respectively). CONCLUSION: Seasonal variations should be considered when
      measuring for 25(OH)D serum levels and treating vitD deficiency.

PMID- 25977394
TI  - Blank space.

PMID- 25977395
TI  - Correction.

PMID- 25977396
TI  - Higher sensitivity of immunohistochemistry for bona fide diagnosis of dog
      Leishmania (Viannia) braziliensis-driven American tegumentary leishmaniasis:
      description of an optimized immunohistochemistry method.
AB  - BACKGROUND: The in situ detection of parasite antigens in tissue sections by
      immunohistochemistry (IHC) is a diagnostic alternative for human American
      tegumentary leishmaniasis (ATL), but has not been used for the diagnosis of
      cutaneous lesions in dogs with ATL. This study describes the results of IHC for
      the detection of amastigote forms and other Leishmania sp. antigen-positive cells
      and compares the results of IHC, histopathology and cytopathology for the
      diagnosis of canine ATL. In addition, possible cross-reactivity with
      sporotrichosis is analyzed. METHODS: Forty paraffin-embedded biopsies and 40
      smears of cutaneous lesions from dogs with ATL, confirmed by isolation and
      characterization of Leishmania (Viannia) braziliensis, and 40 paraffin-embedded
      biopsies of cutaneous lesions from dogs with sporotrichosis, confirmed by
      isolation of Sporothrix schenckii in culture (control group), were studied.
      RESULTS: Immunohistochemistry was more sensitive in detecting amastigote forms
      than cytopathology and histopathology, with a positivity rate of 70% (n=28)
      versus 37.5% and 22.5% for histopathology and cytopathology, respectively.
      Cytoplasmic staining of mononuclear and endothelial cells was detected by IHC,
      which was highly specific since no cytoplasmic staining of these cells or
      staining of fungal structures was observed in sporotrichosis fragments.
      CONCLUSIONS: In view of the higher sensitivity of IHC in detecting Leishmania sp.
      antigen and patterns of positivity for Leishmania sp. antigen compared to
      histopathology or cytopathology and the absence of cross-reactions with
      sporotrichosis, we recommend this technique for the diagnosis of canine
      tegumentary leishmaniasis.

PMID- 25977398
TI  - Genome sequencing reveals novel deletions associated with secondary resistance to
      pyrazinamide in MDR Mycobacterium tuberculosis.
AB  - OBJECTIVES: Detection of pyrazinamide resistance in Mycobacterium tuberculosis
      isolates presents significant challenges in settings with no dominant clonal
      lineages, such as Australia. We assessed the utility of WGS versus standard PCR
      amplification assays for the characterization of pyrazinamide resistance in MDR
      TB isolates identified in New South Wales, Australia, over an 8 year period.
      METHODS: PCR amplicon sequencing was used to identify molecular markers
      associated with antibiotic resistance in pyrazinamide-resistant MDR-TB isolates
      recovered by the New South Wales Mycobacterium Reference Laboratory between 2007
      and 2014. WGS was subsequently performed on two isolates for which pncA
      amplification failed. RESULTS: WGS identified two novel genomic deletions
      associated with in vitro resistance to pyrazinamide in MDR-TB. One isolate also
      carried a second deletion involving the genes dfrA and thyA associated with
      resistance to para-aminosalicylic acid. CONCLUSIONS: Steadily decreasing
      sequencing costs are increasing the appeal of WGS as an alternative approach for
      detecting complex patterns of pyrazinamide resistance in MDR-TB.

PMID- 25977399
TI  - Description of an original integron encompassing blaVIM-2, qnrVC1 and genes
      encoding bacterial group II intron proteins in Pseudomonas aeruginosa.
AB  - OBJECTIVES: A burn unit of a hospital in Tunis underwent an endemic situation
      caused by imipenem-resistant Pseudomonas aeruginosa. For nine non-repetitive
      isolates of a clonal VIM-2-producing strain, the blaVIM-2 genetic background was
      characterized and the associated qnrVC1 gene molecularly analysed. METHODS: The
      imipenem resistance mechanism was investigated by phenotypic and molecular tests,
      and resistance transfer was studied by conjugation and transformation
      experiments. The integron's structure was characterized by sequencing, and qnrVC1
      expression was explored after cloning experiments. RESULTS: The nine VIM-2
      producing strains were collected from eight patients and one environmental
      sample. All transfer assays failed, suggesting a chromosomal location of blaVIM
      2. This latter was found to be part of a class 1 integron of ~7500 bp, which also
      contains blaOXA-2, aadA1 and two copies of the aadB, arr-6 and qnrVC1 genes.
      qnrVC1 exhibited higher homology with the chromosomally encoded qnr genes of
      Vibrionaceae than with plasmid-mediated qnr genes of Enterobacteriaceae. The
      qnrVC1 gene cassette possesses a promoter allowing its expression, and it
      conferred decreased fluoroquinolone susceptibility to Escherichia coli.
      Additionally, on the same integron, genes encoding an uncommon group IIC-attC
      intron were detected. CONCLUSIONS: A VIM-2-producing P. aeruginosa outbreak led
      us to characterize an integron harbouring a qnrVC1 cassette and a new group IIC
      attC intron. This is the first known description of a qnr determinant in a P.
      aeruginosa strain. Its presence conferred a low level of resistance to quinolones
      in E. coli, which might favour the emergence of highly resistant mutants.

PMID- 25977397
TI  - A novel gene, optrA, that confers transferable resistance to oxazolidinones and
      phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of
      human and animal origin.
AB  - OBJECTIVES: The oxazolidinone-resistant Enterococcus faecalis E349 from a human
      patient tested negative for the cfr gene and 23S rRNA mutations. Here we report
      the identification of a novel oxazolidinone resistance gene, optrA, and a first
      investigation of the extent to which this gene was present in E. faecalis and
      Enterococcus faecium from humans and food-producing animals. METHODS: The
      resistance gene optrA was identified by whole-plasmid sequencing and subsequent
      cloning and expression in a susceptible Enterococcus host. Transformation and
      conjugation assays served to investigate the transferability of optrA. All optrA
      positive E. faecalis and E. faecium isolates of human and animal origin were
      analysed for their MICs and their genotype, as well as the location of optrA.
      RESULTS: The novel plasmid-borne ABC transporter gene optrA from E. faecalis E349
      conferred combined resistance or elevated MICs (when no clinical breakpoints were
      available) to oxazolidinones (linezolid and tedizolid) and phenicols
      (chloramphenicol and florfenicol). The corresponding conjugative plasmid pE349,
      on which optrA was located, had a size of 36 331 bp and also carried the phenicol
      exporter gene fexA. The optrA gene was functionally expressed in E. faecalis, E.
      faecium and Staphylococcus aureus. It was detected more frequently in E. faecalis
      and E. faecium from food-producing animals (20.3% and 5.7%, respectively) than
      from humans (4.2% and 0.6%, respectively). CONCLUSIONS: Enterococci with elevated
      MICs of linezolid and tedizolid should be tested not only for 23S rRNA mutations
      and the gene cfr, but also for the novel resistance gene optrA.

PMID- 25977400
TI  - Non-susceptibility to ceftaroline in healthcare-associated multiresistant MRSA in
      Eastern Australia.

PMID- 25977402
TI  - Coenzyme Q10 and statin-related myopathy.
AB  - Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase, which is involved in the production of mevalonic acid in the
      cholesterol biosynthesis pathway. This pathway also results in the production of
      other bioactive molecules including coenzyme Q10 (also known as ubiquinone or
      ubidecarenone). Coenzyme Q10 is a naturally-occurring coenzyme with antioxidant
      effects that is involved in electron transport in mitochondria and is thought to
      play a role in energy transfer in skeletal muscle. Muscle-related problems are a
      frequently reported adverse effect of statins, and it has been hypothesised that
      a reduced endogenous coenzyme Q10 concentration is a cause of statin-induced
      myopathy. Coenzyme Q10 supplementation has therefore been proposed to reduce the
      adverse muscular effects sometimes seen with statins. Here, we consider whether
      coenzyme Q10 has a place in the management of statin-induced myopathy.

PMID- 25977401
TI  - Bedaquiline susceptibility testing of Mycobacterium tuberculosis in an automated
      liquid culture system.
AB  - OBJECTIVES: The objective of this study was to evaluate the performance of the
      BACTEC MGIT960 system to test the susceptibility to bedaquiline for Mycobacterium
      tuberculosis complex. METHODS: We determined the quality control (QC) range of
      bedaquiline using the M. tuberculosis H37Rv reference strain and the
      epidemiological cut-off (ECOFF) in MGIT960 and on Middlebrook 7H11 agar (M7H11)
      using 47 strains from bedaquiline treatment-naive patients. The accuracy of
      MGIT960 was evaluated versus M7H11 using 74 'probably susceptible to bedaquiline'
      and 18 'probably resistant to bedaquiline' strains. Repeatability and
      reproducibility of MGIT960 were assessed using five strains showing different
      resistance levels. RESULTS: The QC range for the H37Rv strain was between 0.125
      and 0.50 mg/L. The WT MIC distribution ranged from <=0.03 to 1.00 mg/L in MGIT960
      and from <=0.008 to 0.25 mg/L on M7H11 with suggested ECOFFs of 1.00 and 0.25
      mg/L, respectively. Applying these ECOFFs, the probably susceptible and probably
      resistant strains were distinguishable by both methods, albeit with only a 2-fold
      increased MIC for one of the resistant strains compared with the ECOFF.
      Intermethod agreement to classify the isolates was excellent (100%). All
      replicates in the repeatability and reproducibility experiments fell within the
      normal range. CONCLUSIONS: The MGIT960 system proved to be highly stable,
      reproducible and accurate relative to the M7H11 agar method for determining the
      bedaquiline MIC. The small margin between the suggested ECOFF and the lowest MIC
      for the mutant strains risks making both methods prone to discordant results.
      Further validation in clinical settings linked to treatment outcome data is
      needed.

PMID- 25977403
TI  - Drugs for the doctor's bag: 1-adults.
AB  - In the past, GPs carried a range of medicines for acute or emergency visits,
      which is now less necessary where paramedics are trained and equipped, and where
      emergency transfers to hospital are rapid. Indeed, acute services and ambulance
      trusts in some areas may discourage GPs from attending emergencies as it could
      delay patient transfers. However, there is still a need for some GPs to carry a
      range of medicines for use in acute situations when on home visits. What to
      include in the GP's bag is determined by the medical conditions likely to be met;
      medicines the GP is confident and competent to use; storage requirements and
      shelf-lives of drugs; ambulance paramedic cover and the proximity of the nearest
      hospital. Here we suggest medicines suitable for GPs for emergency or acute
      treatment of adult patients, updating our previous advice and including the
      underlying guideline recommendations for their use. A later article will cover
      treatment for children. The intention is not to imply that every doctor should
      carry every drug mentioned. Instead, we aim to highlight some of the key
      treatments and suggest choices in some of the more common clinical scenarios that
      GPs may have to deal with in everyday practice, which may be prior to referral to
      secondary care. Each section ends with a list of drug recommendations for the
      doctor's bag; drugs may be referred to in several sections but are only listed in
      one section to avoid repetition. The article does not provide recommendations for
      drugs to be stocked for use in routine clinical practice in the surgery (e.g. for
      minor surgery) or for drugs to be held by out-of-hours primary care services.
      Separate guidance and advice is available on drugs suitable for use by those
      providing out-of-hours primary care services. For example, in England a national
      out-of-hours core formulary contains the minimum list of drugs that patients
      should be able to access.

PMID- 25977404
TI  - Association of treponeme species with atypical foot lesions in goats.
AB  - Five UK goat farms with high levels of lameness (prevalence 14-67 per cent) were
      investigated. On two farms (farms 1 and 2), the animals presented with typical
      footrot lesions. The remaining three farms (farms 3, 4 and 5) presented with
      infected lesions on the foot that did not resemble footrot. These lesions were
      observed to start from the white line or sole but the interdigital space was
      rarely affected. Swabs were processed by PCR to assess the presence of
      Dichelobacter nodosus and three specific treponeme groups (group 1: Treponema
      medium/Treponema vincentii-like, group 2: Treponema phagedenis-like and group 3:
      Treponema denticola/Treponema putidum-like) that are reported to be associated
      with bovine digital dermatitis and contagious ovine digital dermatitis. On farms
      1 and 2, 85.7 per cent of samples were found to be positive for D nodosus while
      only 9.5 per cent were positive for treponeme groups 1, 2 and 3. In contrast, 5.3
      per cent of samples from farms 3, 4 and 5 were positive for D nodosus, while
      34.2, 68.4 and 36.8 per cent of samples from these farms tested positive for
      treponeme groups 1, 2 and 3, respectively. T medium/T vincentii-like, T
      phagedenis-like and T denticola/T putidum-like treponemes were detected on foot
      lesions of lame goats suggesting that they have a role in the aetiology of this
      lameness, which has not previously been described in dairy goats. 

PMID- 25977405
TI  - Automating the generation of lexical patterns for processing free text in
      clinical documents.
AB  - OBJECTIVE: Many tasks in natural language processing utilize lexical pattern
      matching techniques, including information extraction (IE), negation
      identification, and syntactic parsing. However, it is generally difficult to
      derive patterns that achieve acceptable levels of recall while also remaining
      highly precise. MATERIALS AND METHODS: We present a multiple sequence alignment
      (MSA)-based technique that automatically generates patterns, thereby leveraging
      language usage to determine the context of words that influence a given target.
      MSAs capture the commonalities among word sequences and are able to reveal areas
      of linguistic stability and variation. In this way, MSAs provide a systemic
      approach to generating lexical patterns that are generalizable, which will both
      increase recall levels and maintain high levels of precision. RESULTS: The MSA
      generated patterns exhibited consistent F1-, F.5-, and F2- scores compared to two
      baseline techniques for IE across four different tasks. Both baseline techniques
      performed well for some tasks and less well for others, but MSA was found to
      consistently perform at a high level for all four tasks. DISCUSSION: The
      performance of MSA on the four extraction tasks indicates the method's
      versatility. The results show that the MSA-based patterns are able to handle the
      extraction of individual data elements as well as relations between two concepts
      without the need for large amounts of manual intervention. CONCLUSION: We
      presented an MSA-based framework for generating lexical patterns that showed
      consistently high levels of both performance and recall over four different
      extraction tasks when compared to baseline methods.

PMID- 25977406
TI  - Intervening early in children with bipolar disorder: is there a pot at the end of
      the Rainbow?

PMID- 25977408
TI  - Nicotine Metabolite Ratio Is Associated With Lozenge Use But Not Quitting in
      Smokeless Tobacco Users.
AB  - INTRODUCTION: The nicotine metabolite ratio (NMR) of 3'-hydroxycotinine to
      cotinine is a noninvasive marker of the rate of nicotine metabolism. Fast
      metabolism (ie, a high NMR) is associated with lower cigarette smoking abstinence
      rates using transdermal nicotine replacement. We evaluated whether the NMR can be
      used to predict self-reported nicotine lozenge use and tobacco abstinence among
      smokeless tobacco users treated for tobacco dependence. METHODS: This was a
      secondary analysis of data from one arm of a large trial. Participants received
      quitting support materials and 4-mg nicotine lozenges by mail plus three coaching
      phone calls. Saliva kits were mailed for collection of saliva samples, which were
      analyzed for cotinine and 3'-hydroxycotinine. Self-reported tobacco and lozenge
      use were assessed at 3 months. Analyses were performed using Spearman rank
      correlation and logistic regression. RESULTS: Of the 160 saliva collection kits
      mailed, 152 were returned. The NMR was not significantly correlated with the
      baseline amount of smokeless tobacco used, the number of years of tobacco use, or
      the level of tobacco dependence as measured by the Severson Smokeless Tobacco
      Dependency Scale. The NMR was positively correlated with lozenge use (r = 0.21, P
      = .015), but it did not predict self-reported 7-day point prevalence abstinence
      at 3 months. CONCLUSIONS: Fast metabolizers may need to self-administer more
      nicotine replacement in the form of nicotine lozenges to achieve the same
      clinical response achieved by slower metabolizers using fewer lozenges.

PMID- 25977410
TI  - Draft Genome Sequence of Lactobacillus rhamnosus CLS17.
AB  - We announce the draft genome sequence of the type strain Lactobacillus rhamnosus
      CLS17 (2,889,314 nt, with a GC content of 46.8%), which is one of the most
      prevalent lactic acid bacteria present during the manufacturing process of dairy
      products; the genome consists of 71 large contigs (>100 bp in size). It contains
      2,643 protein-coding sequences, single predicted copies of the 5S, 16S, and 23S
      rRNA genes, and 51 predicted tRNAs. 

PMID- 25977409
TI  - Mathematical Modeling in Tobacco Control Research: Initial Results From a
      Systematic Review.
AB  - OBJECTIVES: The US Food and Drug Administration has expressed interest in using
      mathematical models to evaluate potential tobacco policies. The goal of this
      systematic review was to synthesize data from tobacco control studies that employ
      mathematical models. METHODS: We searched five electronic databases on July 1,
      2013 to identify published studies that used a mathematical model to project a
      tobacco-related outcome and developed a data extraction form based on the ISPOR
      SMDM Modeling Good Research Practices. We developed an organizational framework
      to categorize these studies and identify models employed across multiple papers.
      We synthesized results qualitatively, providing a descriptive synthesis of
      included studies. RESULTS: The 263 studies in this review were heterogeneous with
      regard to their methodologies and aims. We used the organizational framework to
      categorize each study according to its objective and map the objective to a model
      outcome. We identified two types of study objectives (trend and
      policy/intervention) and three types of model outcomes (change in tobacco use
      behavior, change in tobacco-related morbidity or mortality, and economic impact).
      Eighteen models were used across 118 studies. CONCLUSIONS: This paper extends
      conventional systematic review methods to characterize a body of literature on
      mathematical modeling in tobacco control. The findings of this synthesis can
      inform the development of new models and the improvement of existing models,
      strengthening the ability of researchers to accurately project future tobacco
      related trends and evaluate potential tobacco control policies and interventions.
      These findings can also help decision-makers to identify and become oriented with
      models relevant to their work.

PMID- 25977411
TI  - Complete Genome Sequence of Scardovia inopinata JCM 12537T, Isolated from Human
      Dental Caries.
AB  - Scardovia inopinata JCM 12537(T) was isolated from human dental caries. Here, we
      report the complete genome sequence of this organism. This paper is the first
      report to demonstrate the fully sequenced and completely annotated genome of an
      S. inopinata strain. 

PMID- 25977412
TI  - Genome Sequence of the Electrogenic Petroleum-Degrading Thalassospira sp. Strain
      HJ.
AB  - We present the draft genome of the petroleum-degrading Thalassospira sp. strain
      HJ, isolated from tidal marine sediment. Knowledge of this genomic information
      will inform studies on electrogenesis and means to degrade environmental organic
      contaminants, including compounds found in petroleum. 

PMID- 25977413
TI  - Complete Genome Sequence of Parascardovia denticolens JCM 12538T, Isolated from
      Human Dental Caries.
AB  - Parascardovia denticolens JCM 12538(T) was isolated from human dental caries.
      Here, we report the complete genome sequence of this organism. This paper is the
      first report demonstrating the completely sequenced and assembled genome of P.
      denticolens. 

PMID- 25977414
TI  - Draft Genome Sequence of Methylobacterium radiotolerans, a DDE-Degrading and
      Plant Growth-Promoting Strain Isolated from Cucurbita pepo.
AB  - We announce the draft genome of Methylobacterium radiotolerans, a Gram-negative
      bacterium isolated from Cucurbita pepo roots. This strain shows 2,2-bis(p
      chlorophenyl)-1,1-dichloroethylene (DDE)-degrading potential and plant growth
      promoting capacities. Analyses of its 6.8-Mb genome will improve our
      understanding of DDE-degradation pathways and aid in the deployment of
      phytoremediation technologies to remediate DDE-contaminated soils. 

PMID- 25977415
TI  - Sphingomonas taxi, Isolated from Cucurbita pepo, Proves to Be a DDE-Degrading and
      Plant Growth-Promoting Strain.
AB  - The draft genome of Sphingomonas taxi, a strain of the Sphingomonadaceae isolated
      from Cucurbita pepo root tissue, is presented. This Gram-negative bacterium shows
      2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE)-degrading potential and plant
      growth-promoting capacities. An analysis of its 3.9-Mb draft genome will enhance
      the understanding of DDE-degradation pathways and phytoremediation applications
      for DDE-contaminated soils. 

PMID- 25977416
TI  - Draft Genome Sequence of Norvancomycin-Producing Strain Amycolatopsis orientalis
      CPCC200066.
AB  - Amycolatopsis orientalis CPCC200066 is an actinomycete that can produce the
      glycopeptide antibiotic norvancomycin, which has significant inhibitory activity
      against Gram-positive cocci and bacilli. Here, we report the draft genome
      sequence of A. orientalis CPCC200066 and identified the genes involved in
      norvancomycin biosynthesis. 

PMID- 25977417
TI  - Draft Genome Sequence of Pantoea anthophila Strain 11-2 from Hypersaline Lake
      Laysan, Hawaii.
AB  - Most Pantoea spp. have been isolated from plant sources or clinical samples.
      However, we cultivated Pantoea anthophila 11-2 from hypersaline water from the
      lake on Laysan, Northwestern Hawaiian Islands. Draft genome sequencing of 11-2
      provides a molecular basis for studies in evolution and pathogenicity in Pantoea
      spp. 

PMID- 25977418
TI  - Complete Genome Sequence of Cupriavidus basilensis 4G11, Isolated from the Oak
      Ridge Field Research Center Site.
AB  - Cupriavidus basilensis 4G11 was isolated from groundwater at the Oak Ridge Field
      Research Center (FRC) site. Here, we report the complete genome sequence and
      annotation of Cupriavidus basilensis 4G11. The genome contains 8,421,483 bp,
      7,661 predicted protein-coding genes, and a total GC content of 64.4%. 

PMID- 25977419
TI  - Complete genome sequence of porcine circovirus strain 102 with a novel mutation,
      isolated from hunan province, china.
AB  - Porcine circovirus 2 (PCV2) strain 102 belongs to the PCV2b-1C subtype, and its
      sole structural protein (Cap) exhibits high homology with that of other PCV2b
      isolates reported in South Korea, China, and the United States. Strain 102
      contains a new mutation (R37H) in the domain of the nuclear localization signal
      (NLS) of the Cap. 

PMID- 25977420
TI  - Complete genome sequence of a carnation mottle virus infecting hop plants.
AB  - The Carnation mottle virus (CarMV) is a single positive-strand RNA virus
      belonging to the genus Carmovirus. The major natural host for CarMV is the
      carnation. In this study, using transcriptome data, we provide for the first time
      a nearly complete genome sequence of CarMV infecting hop plants. 

PMID- 25977421
TI  - Genome Sequences of 11 Shiga Toxin-Producing Escherichia coli Strains.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains are a common cause of both
      sporadic infection and outbreaks of enteric disease in humans. Here, we present
      draft genome sequences of 11 STEC strains of different serotypes (O145, O121,
      O26, O177, and O-type unknown), that have been isolated from patients with
      enteric disease of various degrees of severity, in the years 2001 to 2014 at St.
      Olavs Hospital in Trondheim, Norway. 

PMID- 25977422
TI  - Draft Genome Sequence of Phenylobacterium immobile Strain E (DSM 1986), Isolated
      from Uncontaminated Soil in Ecuador.
AB  - We report the draft genome sequence of 3.3 Mb and the sequence (19.2 kb) of a
      natural plasmid isolated from Phenylobacterium immobile strain E (DSM 1986), able
      to degrade xenobiotic compounds as the sole carbon source. The sequences reveal a
      large number of novel Rieske nonheme iron aromatic ring-hydroxylating oxygenases
      (RHOs). 

PMID- 25977423
TI  - Draft Genome Sequences of Four NDM-1-Producing Klebsiella pneumoniae Strains from
      a Health Care Facility in Northern California.
AB  - We report the draft genome sequences of Klebsiella pneumoniae strains from four
      patients at a northern California health care facility. All strains contained the
      New Delhi metallo-beta-lactamase (NDM1) carbapenemase with extended antibiotic
      resistance, including resistance to expanded-spectrum cephalosporins, imipenem,
      ertapenem, and meropenem. NDM gene alignments revealed that the resistance was
      plasmid encoded. 

PMID- 25977424
TI  - Draft Whole-Genome Sequence of Lactobacillus fermentum LfQi6, Derived from the
      Human Microbiome.
AB  - We report a 2.21-Mbp draft whole-genome sequence of Lactobacillus fermentum Qi6
      (LfQi6). This strain demonstrates activity against pathogenic biofilms, enhances
      the skin barrier, and upregulates innate immune defenses. The genome sequence
      information of this strain will help to identify molecules that hold promise for
      the discovery of novel therapeutics for dermatological disorders. 

PMID- 25977425
TI  - Draft Genome Sequence of Alicycliphilus sp. B1, an N-Acylhomoserine Lactone
      Producing Bacterium, Isolated from Activated Sludge.
AB  - We report here the draft genome sequence of Alicycliphilus sp. B1, isolated from
      activated sludge in a wastewater treatment plant of an electronic component
      factory as an N-acylhomoserine lactone-producing strain. The draft genome is
      7,465,959 bp in length, with 59 large contigs. About 7,391 protein-coding genes,
      82 tRNAs, and 13 rRNAs are predicted from this assembly. 

PMID- 25977426
TI  - Draft Genome Sequences of 10 Microbacterium spp., with Emphasis on Heavy Metal
      Contaminated Environments.
AB  - Microbacterium spp. isolated from heavy metal (HM)-contaminated environments
      (soil and plants) can play a role in mobilization processes and in the
      phytoextraction of HM. Here, we report the whole-genome sequences and annotation
      of 10 Microbacterium spp. isolated from both HM-contaminated and -noncontaminated
      compartments. 

PMID- 25977427
TI  - Whole-Genome Sequence of Aquamicrobium sp. Strain SK-2, a Polychlorinated
      Biphenyl-Utilizing Bacterium Isolated from Sewage Sludge.
AB  - Here, we report the whole-genome sequence of Aquamicrobium sp. strain SK-2, a
      bacterium which can use 2,2',4,4',5,5'-hexachlorobiphenyl as the sole carbon
      source for its growth. An approximately 9.23-Mb genome sequence of SK-2 will
      greatly facilitate research efforts regarding the study of the polychlorinated
      biphenyl (PCB) degradation mechanism. 

PMID- 25977428
TI  - Complete Genome Sequences of Caldicellulosiruptor sp. Strain Rt8.B8,
      Caldicellulosiruptor sp. Strain Wai35.B1, and "Thermoanaerobacter
      cellulolyticus".
AB  - The genus Caldicellulosiruptor contains extremely thermophilic, cellulolytic
      bacteria capable of lignocellulose deconstruction. Currently, complete genome
      sequences for eleven Caldicellulosiruptor species are available. Here, we report
      genome sequences for three additional Caldicellulosiruptor species: Rt8.B8 DSM
      8990 (New Zealand), Wai35.B1 DSM 8977 (New Zealand), and "Thermoanaerobacter
      cellulolyticus" strain NA10 DSM 8991 (Japan). 

PMID- 25977429
TI  - Draft Genome Sequence of Extensively Drug-Resistant Acinetobacter baumannii
      Strain CUAB1 from a Patient in Hong Kong, China.
AB  - We report the draft genome sequence of an extensively drug-resistant strain of
      Acinetobacter baumannii, CUAB1, isolated from a patient in a local Hong Kong
      hospital. MIC testing was performed, and genes previously associated with drug
      resistance were located. 

PMID- 25977430
TI  - Genome Sequence of Bacillus thuringiensis Strain Btm27, an Egyptian Isolate
      Highly Toxic to Cotton Leafworm.
AB  - Bacillus thuringiensis is a potent microbial control agent against insect pests.
      Here, we present the draft genome of the Egyptian strain Btm27 that shows high
      toxicity toward the cotton leafworm. The genome contains three insecticidal genes
      cry1Ac9, cry2Ab1, and vip3V that have been implicated in conferring toxicity
      toward lepidoptera. 

PMID- 25977431
TI  - Draft Genome Sequence of Burkholderia andropogonis Type Strain ICMP2807, Isolated
      from Sorghum bicolor.
AB  - Here, we report the draft genome sequence of Burkholderia andropogonis ICMP2807,
      a phytopathogenic bacterium isolated from Sorghum bicolor plants in the United
      States. 

PMID- 25977432
TI  - Draft Genome Sequence of Staphylococcus carnosus subsp. utilis LTH 7013, Isolated
      from South Tyrolean Ham.
AB  - Staphylococcus carnosus is used as a starter culture in meat fermentation, where
      it contributes to color formation and produces aromatic compounds. Here, we
      report the first draft genome sequence of an S. carnosus subsp. utilis strain,
      LTH 7013, isolated from South Tyrolean ham, with potential application as a
      starter culture. 

PMID- 25977433
TI  - Draft Genome Sequence of Erythrobacter vulgaris Strain O1, a Glycosyl Hydrolase
      Producing Bacterium.
AB  - Erythrobacter vulgaris strain O1, a moderate halophile, was isolated from a beach
      in Johor, Malaysia. Here, we present the draft genome and suggest potential
      applications of this bacterium. 

PMID- 25977434
TI  - Complete Genome Assemblies for Two Single-Chromosome Vibrio cholerae Isolates,
      Strains 1154-74 (Serogroup O49) and 10432-62 (Serogroup O27).
AB  - Here, we report the completed genome sequences for two non-O1/non-O139 Vibrio
      cholerae isolates. Each isolate has only a single chromosome, as opposed to the
      normal paradigm of two chromosomes found in all other V. cholerae isolates. 

PMID- 25977435
TI  - Whole-Genome Sequence and Annotation of Octopine-Utilizing Pseudomonas kilonensis
      (Previously P. fluorescens) Strain 1855-344.
AB  - Here, we report the whole-genome sequence and annotation of Pseudomonas
      kilonensis 1855-344 (previously known as P. fluorescens 1855-344). The genome
      contains an octopine oxidase gene cluster consistent with the ability to utilize
      octopine. A biosynthetic gene cluster was identified for mangotoxin and aryl
      polyene using the antiSMASH server. 

PMID- 25977436
TI  - Draft Genome Sequences of Two Clinical Isolates of Mycobacterium tuberculosis
      from Sputum of Kazakh Patients.
AB  - Here, we report the draft genome sequences of two clinical isolates of
      Mycobacterium tuberculosis (MTB-476 and MTB-489) isolated from sputum of Kazakh
      patients. 

PMID- 25977437
TI  - Draft Genome Sequence of the Nonmarine Agarolytic Bacterium Cellvibrio sp. OA
      2007.
AB  - Cellvibrio sp. OA-2007 is a Gram-negative, aerobic, and agarolytic bacterium
      isolated from activated sludge. We present the draft genome sequence of strain OA
      2007, composed of 97 contigs, totaling 4,595,379 bp in size, and containing 4,094
      open reading frames, with a G+C content of 47.71%. 

PMID- 25977438
TI  - Draft Genome Sequence of Oleiagrimonas soli 3.5XT, a Type Species in a Newly
      Identified Genus, Isolated from an Oil Field in China.
AB  - Oleiagrimonas gudaosoli 3.5X(T) was isolated from an oil field and identified as
      a new member of a novel genus. The draft genome sequence of this strain, which
      comprises 3,379,958 bp encoding 3,010 open reading frames (ORFs), can provide
      insight into the life style of this newly identified genus in petroleum
      contaminated soil. 

PMID- 25977439
TI  - Draft Genome Sequences of Six Different Staphylococcus epidermidis Clones,
      Isolated Individually from Preterm Neonates Presenting with Sepsis at Edinburgh's
      Royal Infirmary.
AB  - Herein, we report the draft genome sequences of six individual Staphylococcus
      epidermidis clones, cultivated from blood taken from different preterm neonatal
      sepsis patients at the Royal Infirmary, Edinburgh, Scotland, United Kingdom. 

PMID- 25977440
TI  - Draft Genome Sequence of Anaeromyxobacter sp. Strain PSR-1, an Arsenate-Respiring
      Bacterium Isolated from Arsenic-Contaminated Soil.
AB  - Here, we report a draft genome sequence of Anaeromyxobacter sp. strain PSR-1, an
      arsenate-respiring bacterium isolated from arsenic-contaminated soil. It
      contained three distinct arsenic resistance gene clusters (ars operons), while no
      respiratory arsenate reductase gene (arr) was identified. 

PMID- 25977441
TI  - Draft Genome Sequence of Pseudomonas abietaniphila KF701 (NBRC110664), a
      Polychlorinated Biphenyl-Degrading Bacterium Isolated from Biphenyl-Contaminated
      Soil.
AB  - Pseudomonas abietaniphila KF701 utilizes biphenyl as a sole source of carbon and
      degrades polychlorinated biphenyls (PCBs). Here, we report the 6,886,250-bp draft
      genome sequence of KF701, which contains 6,315 coding sequences and 59.4 mol% G+C
      content. The strain possesses genes for biphenyl catabolism and other genes that
      mediate the degradation of benzoate, salicylate, and phenol. 

PMID- 25977442
TI  - Draft Genome Sequences of Five Legionella pneumophila Strains Isolated from
      Environmental Water Samples.
AB  - Legionella pneumophila is the causative agent of legionellosis. Here, we report
      the draft genome sequences of five L. pneumophila strains, Bnt314, Ofk308,
      Twr292, Ymg289, and Ymt294, isolated from environmental water samples.
      Comparative analyses of these genomes may reveal the survival mechanisms and
      virulence of L. pneumophila in the natural environment. 

PMID- 25977443
TI  - Draft Genome Sequence of the Thermophile Thermus filiformis ATCC 43280, Producer
      of Carotenoid-(Di)glucoside-Branched Fatty Acid (Di)esters and Source of
      Hyperthermostable Enzymes of Biotechnological Interest.
AB  - Here, we present the draft genome sequence of Thermus filiformis strain ATCC
      43280, a thermophile bacterium capable of producing glycosylated carotenoids
      acylated with branched fatty acids and enzymes of biotechnological potential. 

PMID- 25977444
TI  - The polymorphic terminal-loop of pre-miR-1307 binding with MBNL1 contributes to
      colorectal carcinogenesis via interference with Dicer1 recruitment.
AB  - Colorectal cancer (CRC) is one of the most common malignancies in the world.
      Studies have demonstrated that single nucleotide polymorphisms (SNPs) in microRNA
      genes (miRSNPs) are involved in the occurrence of cancers. However, the
      relationship between the miRSNPs within the terminal-loops of microRNA precursors
      and the development of CRC is still largely unknown. In this study, we found that
      a miRSNP rs7911488 T>C in the terminal-loop of pre-miR-1307 was significantly
      associated with the occurrence of CRC. The C allele of rs7911488 is more
      prevalent in CRC patients than in healthy controls (P < 0.001), and this C allele
      prevalence is related to low level of miR-1307 expression. A RNA-binding protein
      MBNL1 binds with a 'UGCUGC' motif in the terminal-loop of the C-allelic pre-miR
      1307 and blocks Dicer processing, resulting in downregulation of miR-1307
      expression. Consequently, the antiapoptosis protein Bcl2, which is a direct
      target of miR-1307, is overexpressed in CRC. Furthermore, MBNL1 participates in
      processing of both C-allelic and T-allelic pre-miR-1307. In summary, our results
      show that rs7911488 C-allelic pre-miR-1307 binds to MBNL1 and infers with Dicer
      processing, leading to reduced miR-1307 and increased Bcl2 expression, thus
      representing an important process in the initiation of CRC. 

PMID- 25977445
TI  - Occupational exposures and lung cancer risk among Minnesota taconite mining
      workers.
AB  - OBJECTIVE: To examine the association between employment duration, elongate
      mineral particle (EMP) exposure, silica exposure and the risk of lung cancer in
      the taconite mining industry. METHODS: We conducted a nested case-control study
      of lung cancer within a cohort of Minnesota taconite iron mining workers employed
      by any of the mining companies in operation in 1983. Lung cancer cases were
      identified by vital records and cancer registry data through 2010. Two age
      matched controls were selected from risk sets of cohort members alive and lung
      cancer free at the time of case diagnosis. Calendar time-specific exposure
      estimates were made for every job and were used to estimate workers' cumulative
      exposures. ORs and 95% CIs were estimated using conditional logistic regression.
      We evaluated total lung cancer risk and risk of histological subtype by total
      work duration and by cumulative EMP, and silica exposure by quartile of the
      exposure distribution. RESULTS: A total of 1706 cases and 3381 controls were
      included in the analysis. After adjusting for work in haematite mining, asbestos
      exposure and sex, the OR for total duration of employment was 0.99 (95% CI 0.96
      to 1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82
      (95% CI 0.57 to 1.19) and 0.97 (95% CI 0.70 to 1.35), respectively. The risk of
      each histological subtype of lung cancer did not change with increasing exposure.
      CONCLUSIONS: This study suggests that the estimated taconite mining exposures do
      not increase the risk of developing lung cancer.

PMID- 25977446
TI  - Occupational and leisure-time physical activity and coronary heart disease.

PMID- 25977447
TI  - Quantification of chromatographic effects of vitamin B supplementation in urine
      and implications for hydration assessment.
AB  - Changes in body water elicit reflex adjustments at the kidney, thus maintaining
      fluid volume homeostasis. These renal adjustments change the concentration and
      color of urine, variables that can, in turn, be used as biomarkers of hydration
      status. It has been suggested that vitamin supplementation alters urine color; it
      is unclear whether any such alteration would confound hydration assessment via
      colorimetric evaluation. We tested the hypothesis that overnight vitamin B2
      and/or B12 supplementation alters urine color as a marker of hydration status.
      Thirty healthy volunteers were monitored during a 3-day euhydrated baseline,
      confirmed via first morning nude body mass, urine specific gravity, and urine
      osmolality. Volunteers then randomly received B2 (n = 10), B12 (n = 10), or B2 +
      B12 (n = 10) at ~200 * recommended dietary allowance. Euhydration was verified on
      trial days (two of the following: body mass +/- 1.0% of the mean of visits 1-3,
      urine specific gravity < 1.02, urine osmolality < 700 mmol/kg). Vitamin purity
      and urinary B2 concentration ([B2]) and [B12] were quantified via
      ultraperformance liquid chromatography. Two independent observers assessed urine
      color using an eight-point standardized color chart. Following supplementation,
      urinary [B2] was elevated; however, urine color was not different between
      nonsupplemented and supplemented trials. For example, in the B2 trial, urinary
      [B2] increased from 8.6 * 10(4) +/- 7.7 * 10(4) to 5.7 * 10(6) +/- 5.3 * 10(6)
      nmol/l (P < 0.05), and urine color went from 4 +/- 1 to 5 +/- 1 (P > 0.05). Both
      conditions met the euhydrated color classification. We conclude that a large
      overnight dose of vitamins B2 and B12 does not confound assessment of euhydrated
      status via urine color. 

PMID- 25977448
TI  - Ascorbic acid abrogates microparticle generation and vascular injuries associated
      with high-pressure exposure.
AB  - We hypothesized that pathological changes associated with elevations in annexin V
      positive microparticles (MPs) following high-pressure exposures can be abrogated
      by ascorbic acid in a murine model. Mice exposed for 2 h to 790-kPa air and
      killed at 2 or 13 h postdecompression exhibited over threefold elevations in
      circulating MPs, as well as subgroups bearing Ly6G, CD41, Ter119, CD31, and CD142
      surface proteins. There was evidence of significant neutrophil activation,
      platelet-neutrophil interactions, and vascular injury to brain, omentum, psoas,
      and skeletal muscles assessed as leakage of high-molecular-weight dextran.
      Prophylactic ascorbic acid (500 mg/kg ip) administration prevented all
      postdecompression neutrophil changes and vascular injuries. Ascorbic acid
      administration immediately after decompression abrogated most changes, but
      evidence of vascular leakage in the brain and skeletal muscle at 13 h
      postdecompression persisted. No significant elevations in these parameters
      occurred after injection of ascorbic acid alone. The findings support the idea
      that MP production occurring with exposures to elevated gas pressure is an
      oxidative stress response and that antioxidants may offer protection from
      pathological effects associated with decompression. 

PMID- 25977449
TI  - Hypoxia signaling during acute lung injury.
AB  - Acute lung injury (ALI) is an inflammatory lung disease that manifests itself in
      patients as acute respiratory distress syndrome and thereby contributes
      significantly to the morbidity and mortality of patients experiencing critical
      illness. Even though it may seem counterintuitive, as the lungs are typically
      well-oxygenated organs, hypoxia signaling pathways have recently been implicated
      in the resolution of ALI. For example, functional studies suggest that
      transcriptional responses under the control of the hypoxia-inducible factor (HIF)
      are critical in optimizing alveolar epithelial carbohydrate metabolism, and
      thereby dampen lung inflammation during ALI. In the present review we discuss
      functional roles of oxygenation, hypoxia and HIFs during ALI, mechanisms of how
      HIFs are stabilized during lung inflammation, and how HIFs can mediate lung
      protection during ALI.

PMID- 25977451
TI  - Modulating exercise-induced hormesis: Does less equal more?
AB  - Hormesis encompasses the notion that low levels of stress stimulate or upregulate
      existing cellular and molecular pathways that improve the capacity of cells and
      organisms to withstand greater stress. This notion underlies much of what we know
      about how exercise conditions the body and induces long-term adaptations. During
      exercise, the body is exposed to various forms of stress, including thermal,
      metabolic, hypoxic, oxidative, and mechanical stress. These stressors activate
      biochemical messengers, which in turn activate various signaling pathways that
      regulate gene expression and adaptive responses. Historically, antioxidant
      supplements, nonsteroidal anti-inflammatory drugs, and cryotherapy have been
      favored to attenuate or counteract exercise-induced oxidative stress and
      inflammation. However, reactive oxygen species and inflammatory mediators are key
      signaling molecules in muscle, and such strategies may mitigate adaptations to
      exercise. Conversely, withholding dietary carbohydrate and restricting muscle
      blood flow during exercise may augment adaptations to exercise. In this review
      article, we combine, integrate, and apply knowledge about the fundamental
      mechanisms of exercise adaptation. We also critically evaluate the rationale for
      using interventions that target these mechanisms under the overarching concept of
      hormesis. There is currently insufficient evidence to establish whether these
      treatments exert dose-dependent effects on muscle adaptation. However, there
      appears to be some dissociation between the biochemical/molecular effects and
      functional/performance outcomes of some of these treatments. Although several of
      these treatments influence common kinases, transcription factors, and proteins,
      it remains to be determined if these interventions complement or negate each
      other, and whether such effects are strong enough to influence adaptations to
      exercise. 

PMID- 25977450
TI  - Seasonal variation in natural abundance of 2H and 18O in urine samples from rural
      Nigeria.
AB  - The doubly labeled water (DLW) method is used to measure free-living energy
      expenditure in humans. Inherent to this technique is the assumption that natural
      abundances of stable isotopes (2)H and (18)O in body water remain constant over
      the course of the measurement period and after elimination of the loading dose of
      DLW will return to the same predose level. To determine variability in the
      natural abundances of (2)H and (18)O in humans living in a region with seasonal
      shifts in rain patterns and sources of drinking water, over the course of 12 mo
      we collected weekly urine samples from four individuals living in southwest
      Nigeria as well as samples of their drinking water. From ongoing regional studies
      of hypertension, obesity, and energy expenditure, we estimated average water
      turnover rate, urine volumes, and sodium and potassium excretion. Results suggest
      that (2)H and (18)O in urine, mean concentrations of urinary sodium and
      potassium, urine volume, and total body turnover differed significantly from dry
      to rainy season. Additionally, seasonal weather variables (mean monthly maximum
      temperatures, total monthly rainfall, and minimum relative humidity) were all
      significantly associated with natural abundances in urine. No seasonal difference
      was observed in drinking water samples. Findings suggest that natural abundances
      in urine may not remain constant as assumed, and studies incorporating DLW
      measurements across the transition of seasons should interpret results with
      caution unless appropriate doses of the tracers are used. 

PMID- 25977452
TI  - Heart failure with preserved ejection fraction: Defining the function of ROS and
      NO.
AB  - The understanding of complex molecular mechanisms underlying heart failure (HF)
      is constantly under revision. Recent research has paid much attention to
      understanding the growing number of patients that exhibit HF symptoms yet have an
      ejection fraction similar to a normal phenotype. Termed heart failure with
      preserved ejection fraction (HFpEF), this novel hypothesis traces its roots to a
      proinflammatory state initiated in part by the existence of comorbidities that
      create a favorable environment for the production of reactive oxygen species
      (ROS). Triggering a cascade that involves reduced nitric oxide (NO) availability,
      elevated ROS levels in the coronary endothelium eventually contribute to
      hypertrophy and increased resting tension in cardiomyocytes. Improved
      understanding of the molecular pathways associated with HFpEF has led to studies
      that concentrate on reducing ROS production in the heart, boosting NO
      availability, and increasing exercise capacity for HFpEF patients. This review
      will explore the latest research into the role of ROS and NO in the progression
      of HFpEF, as well as discuss the encouraging results of numerous therapeutic
      studies. 

PMID- 25977453
TI  - Erratum for Elkomy et al., Pharmacokinetics of prophylactic cefazolin in
      parturients undergoing cesarean delivery.

PMID- 25977455
TI  - Phylogenomic Analysis of Oenococcus oeni Reveals Specific Domestication of
      Strains to Cider and Wines.
AB  - Oenococcus oeni is a lactic acid bacteria species encountered particularly in
      wine, where it achieves the malolactic fermentation. Molecular typing methods
      have previously revealed that the species is made of several genetic groups of
      strains, some being specific to certain types of wines, ciders or regions. Here,
      we describe 36 recently released O. oeni genomes and the phylogenomic analysis of
      these 36 plus 14 previously reported genomes. We also report three genome
      sequences of the sister species Oenococcus kitaharae that were used for
      phylogenomic reconstructions. Phylogenomic and population structure analyses
      performed revealed that the 50 O. oeni genomes delineate two major groups of 12
      and 37 strains, respectively, named A and B, plus a putative group C, consisting
      of a single strain. A study on the orthologs and single nucleotide polymorphism
      contents of the genetic groups revealed that the domestication of some strains to
      products such as cider, wine, or champagne, is reflected at the genetic level.
      While group A strains proved to be predominant in wine and to form subgroups
      adapted to specific types of wine such as champagne, group B strains were found
      in wine and cider. The strain from putative group C was isolated from cider and
      genetically closer to group B strains. The results suggest that ancestral O. oeni
      strains were adapted to low-ethanol containing environments such as overripe
      fruits, and that they were domesticated to cider and wine, with group A strains
      being naturally selected in a process of further domestication to specific wines
      such as champagne. 

PMID- 25977456
TI  - Estimating Gene Expression and Codon-Specific Translational Efficiencies,
      Mutation Biases, and Selection Coefficients from Genomic Data Alone.
AB  - Extracting biologically meaningful information from the continuing flood of
      genomic data is a major challenge in the life sciences. Codon usage bias (CUB) is
      a general feature of most genomes and is thought to reflect the effects of both
      natural selection for efficient translation and mutation bias. Here we present a
      mechanistically interpretable, Bayesian model (ribosome overhead costs Stochastic
      Evolutionary Model of Protein Production Rate [ROC SEMPPR]) to extract meaningful
      information from patterns of CUB within a genome. ROC SEMPPR is grounded in
      population genetics and allows us to separate the contributions of mutational
      biases and natural selection against translational inefficiency on a gene-by-gene
      and codon-by-codon basis. Until now, the primary disadvantage of similar
      approaches was the need for genome scale measurements of gene expression. Here,
      we demonstrate that it is possible to both extract accurate estimates of codon
      specific mutation biases and translational efficiencies while simultaneously
      generating accurate estimates of gene expression, rather than requiring such
      information. We demonstrate the utility of ROC SEMPPR using the Saccharomyces
      cerevisiae S288c genome. When we compare our model fits with previous approaches
      we observe an exceptionally high agreement between estimates of both codon
      specific parameters and gene expression levels ([Formula: see text] in all
      cases). We also observe strong agreement between our parameter estimates and
      those derived from alternative data sets. For example, our estimates of mutation
      bias and those from mutational accumulation experiments are highly correlated
      ([Formula: see text]). Our estimates of codon-specific translational
      inefficiencies and tRNA copy number-based estimates of ribosome pausing time
      ([Formula: see text]), and mRNA and ribosome profiling footprint-based estimates
      of gene expression ([Formula: see text]) are also highly correlated, thus
      supporting the hypothesis that selection against translational inefficiency is an
      important force driving the evolution of CUB. Surprisingly, we find that for
      particular amino acids, codon usage in highly expressed genes can still be
      largely driven by mutation bias and that failing to take mutation bias into
      account can lead to the misidentification of an amino acid's "optimal" codon. In
      conclusion, our method demonstrates that an enormous amount of biologically
      important information is encoded within genome scale patterns of codon usage,
      accessing this information does not require gene expression measurements, but
      instead carefully formulated biologically interpretable models. 

PMID- 25977457
TI  - Phylogenomic Analyses Indicate that Early Fungi Evolved Digesting Cell Walls of
      Algal Ancestors of Land Plants.
AB  - As decomposers, fungi are key players in recycling plant material in global
      carbon cycles. We hypothesized that genomes of early diverging fungi may have
      inherited pectinases from an ancestral species that had been able to extract
      nutrients from pectin-containing land plants and their algal allies
      (Streptophytes). We aimed to infer, based on pectinase gene expansions and on the
      organismal phylogeny, the geological timing of the plant-fungus association. We
      analyzed 40 fungal genomes, three of which, including Gonapodya prolifera, were
      sequenced for this study. In the organismal phylogeny from 136 housekeeping loci,
      Rozella diverged first from all other fungi. Gonapodya prolifera was included
      among the flagellated, predominantly aquatic fungal species in Chytridiomycota.
      Sister to Chytridiomycota were the predominantly terrestrial fungi including
      zygomycota I and zygomycota II, along with the ascomycetes and basidiomycetes
      that comprise Dikarya. The Gonapodya genome has 27 genes representing five of the
      seven classes of pectin-specific enzymes known from fungi. Most of these share a
      common ancestry with pectinases from Dikarya. Indicating functional and sequence
      similarity, Gonapodya, like many Dikarya, can use pectin as a carbon source for
      growth in pure culture. Shared pectinases of Dikarya and Gonapodya provide
      evidence that even ancient aquatic fungi had adapted to extract nutrients from
      the plants in the green lineage. This implies that 750 million years, the
      estimated maximum age of origin of the pectin-containing streptophytes represents
      a maximum age for the divergence of Chytridiomycota from the lineage including
      Dikarya. 

PMID- 25977458
TI  - Analysis of Five Gene Sets in Chimpanzees Suggests Decoupling between the Action
      of Selection on Protein-Coding and on Noncoding Elements.
AB  - We set out to investigate potential differences and similarities between the
      selective forces acting upon the coding and noncoding regions of five different
      sets of genes defined according to functional and evolutionary criteria: 1) two
      reference gene sets presenting accelerated and slow rates of protein evolution
      (the Complement and Actin pathways); 2) a set of genes with evidence of
      accelerated evolution in at least one of their introns; and 3) two gene sets
      related to neurological function (Parkinson's and Alzheimer's diseases). To that
      effect, we combine human-chimpanzee divergence patterns with polymorphism data
      obtained from target resequencing 20 central chimpanzees, our closest relatives
      with largest long-term effective population size. By using the distribution of
      fitness effect-alpha extension of the McDonald-Kreitman test, we reproduce
      inferences of rates of evolution previously based only on divergence data on both
      coding and intronic sequences and also obtain inferences for other classes of
      genomic elements (untranslated regions, promoters, and conserved noncoding
      sequences). Our results suggest that 1) the distribution of fitness effect-alpha
      method successfully helps distinguishing different scenarios of accelerated
      divergence (adaptation or relaxed selective constraints) and 2) the adaptive
      history of coding and noncoding sequences within the gene sets analyzed is
      decoupled. 

PMID- 25977459
TI  - The Origin and Evolution of the Plant Cell Surface: Algal Integrin-Associated
      Proteins and a New Family of Integrin-Like Cytoskeleton-ECM Linker Proteins.
AB  - The extracellular matrix of scaly green flagellates consists of small organic
      scales consisting of polysaccharides and scale-associated proteins (SAPs).
      Molecular phylogenies have shown that these organisms represent the ancestral
      stock of flagellates from which all green plants (Viridiplantae) evolved. The
      molecular characterization of four different SAPs is presented. Three SAPs are
      type-2 membrane proteins with an arginine/alanine-rich short cytoplasmic tail and
      an extracellular domain that is most likely of bacterial origin. The fourth
      protein is a filamin-like protein. In addition, we report the presence of
      proteins similar to the integrin-associated proteins alpha-actinin (in
      transcriptomes of glaucophytes and some viridiplants), LIM-domain proteins, and
      integrin-associated kinase in transcriptomes of viridiplants, glaucophytes, and
      rhodophytes. We propose that the membrane proteins identified are the predicted
      linkers between scales and the cytoskeleton. These proteins are present in many
      green algae but are apparently absent from embryophytes. These proteins represent
      a new protein family we have termed gralins for green algal integrins. Gralins
      are absent from embryophytes. A model for the evolution of the cell surface
      proteins in Plantae is discussed. 

PMID- 25977460
TI  - A Novel 111In-Labeled Anti-Prostate-Specific Membrane Antigen Nanobody for
      Targeted SPECT/CT Imaging of Prostate Cancer.
AB  - Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer
      (PCa) and a promising target for molecular imaging and therapy. Nanobodies
      (single-domain antibodies, VHH) are the smallest antibody-based fragments
      possessing ideal molecular imaging properties, such as high target specificity
      and rapid background clearance. We developed a novel anti-PSMA Nanobody (JVZ-007)
      for targeted imaging and therapy of PCa. Here, we report on the application of
      the (111)In-radiolabeled Nanobody for SPECT/CT imaging of PCa. METHODS: A
      Nanobody library was generated by immunization of a llama with 4 human PCa cell
      lines. Anti-PSMA Nanobodies were captured by biopanning on PSMA-overexpressing
      cells. JVZ-007 was selected for evaluation as an imaging probe. JVZ-007 was
      initially produced with a c-myc-hexahistidine (his) tag allowing purification and
      detection. The c-myc-his tag was subsequently replaced by a single cysteine at
      the C terminus, allowing site-specific conjugation of chelates for radiolabeling.
      JVZ-007-c-myc-his was conjugated to 2-(4-isothiocyanatobenzyl)
      diethylenetriaminepentaacetic acid (p-SCN-DTPA) via the lysines, whereas JVZ-007
      cys was conjugated to maleimide-DTPA via the C-terminal cysteine. PSMA targeting
      was analyzed in vitro by cell-binding experiments using flow cytometry,
      autoradiography, and internalization assays with various PCa cell lines and
      patient-derived xenografts (PDXs). The targeting properties of radiolabeled
      Nanobodies were evaluated in vivo in biodistribution and SPECT/CT imaging
      experiments, using nude mice bearing PSMA-positive PC-310 and PSMA-negative PC-3
      tumors. RESULTS: JVZ-007 was successfully conjugated to DTPA for radiolabeling
      with (111)In at room temperature. (111)In-JVZ007-c-myc-his and (111)In-JVZ007-cys
      internalized in LNCaP cells and bound to PSMA-expressing PDXs and, importantly,
      not to PSMA-negative PDXs and human kidneys. Good tumor targeting and fast blood
      clearance were observed for (111)In-JVZ-007-c-myc-his and (111)In-JVZ-007-cys.
      Renal uptake of (111)In-JVZ-007-c-myc-his was initially high but was efficiently
      reduced by coinjection of gelofusine and lysine. The replacement of the c-myc-his
      tag by the cysteine contributed to a further reduction of renal uptake without
      loss of targeting. PC-310 tumors were clearly visualized by SPECT/CT with both
      tracers, with low renal uptake (<4 percentage injected dose per gram) for (111)In
      JVZ-007-cys already at 3 h after injection. CONCLUSION: We developed an (111)In
      radiolabeled anti-PSMA Nanobody, showing good tumor targeting, low uptake in
      nontarget tissues, and low renal retention, allowing excellent SPECT/CT imaging
      of PCa within a few hours after injection.

PMID- 25977461
TI  - In Vivo Evaluation of 18F-SiFAlin-Modified TATE: A Potential Challenge for 68Ga
      DOTATATE, the Clinical Gold Standard for Somatostatin Receptor Imaging with PET.
AB  - Radiolabeled peptides for tumor imaging with PET that can be produced with kits
      are currently in the spotlight of radiopharmacy and nuclear medicine. The
      diagnosis of neuroendocrine tumors in particular has been a prime example for the
      usefulness of peptides labeled with a variety of different radionuclides. Among
      those, (68)Ga and (18)F stand out because of the ease of radionuclide
      introduction (e.g., (68)Ga isotope) or optimal nuclide properties for PET imaging
      (slightly favoring the (18)F isotope). The in vivo properties of good
      manufacturing practice-compliant, newly developed kitlike-producible (18)F-SiFA-
      and (18)F-SiFAlin- (SiFA = silicon-fluoride acceptor) modified TATE derivatives
      were compared with the current clinical gold standard (68)Ga-DOTATATE for high
      quality imaging of somatostatin receptor-bearing tumors. METHODS: SiFA- and
      SiFAlin-derivatized somatostatin analogs were synthesized and radiolabeled using
      cartridge-based dried (18)F and purified via a C18 cartridge (radiochemical yield
      49.8% +/- 5.9% within 20-25 min) without high-performance liquid chromatography
      purification. Tracer lipophilicity and stability in human serum were tested in
      vitro. Competitive receptor binding affinity studies were performed using AR42J
      cells. The most promising tracers were evaluated in vivo in an AR42J xenograft
      mouse model by ex vivo biodistribution and in vivo PET/CT imaging studies for
      evaluation of their pharmacokinetic profiles, and the results were compared with
      those of the current clinical gold standard (68)Ga-DOTATATE. RESULTS:
      Synthetically easily accessible (18)F-labeled silicon-fluoride acceptor-modified
      somatostatin analogs were developed. They exhibited high binding affinities to
      somatostatin receptor-positive tumor cells (1.88-14.82 nM). The most potent
      compound demonstrated comparable pharmacokinetics and an even slightly higher
      absolute tumor accumulation level in ex vivo biodistribution studies as well as
      higher tumor standardized uptake values in PET/CT imaging than (68)Ga-DOTATATE in
      vivo. The radioactivity uptake in nontumor tissue was higher than for (68)Ga
      DOTATATE. CONCLUSION: The introduction of the novel SiFA building block SiFAlin
      and of hydrophilic auxiliaries enables a favorable in vivo biodistribution
      profile of the modified TATE peptides, resulting in high tumor-to-background
      ratios although lower than those observed with (68)Ga-DOTATATE. As further
      advantage, the SiFA methodology enables a kitlike labeling procedure for (18)F
      labeled peptides advantageous for routine clinical application.

PMID- 25977462
TI  - Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood
      Flow: Implications for Analysis of beta-Amyloid Images.
AB  - Quantification of beta-amyloid (Abeta) in vivo is often accomplished using the
      distribution volume ratio (DVR), based on a simplified reference tissue model. We
      investigated the local relationships between DVR and cerebral blood flow (CBF),
      as well as relative CBF (R1), in nondemented older adults. METHODS: Fifty-five
      nondemented participants (mean age, 78.5 y) in the Baltimore Longitudinal Study
      of Aging underwent (15)O-H2O PET CBF and dynamic (11)C-PiB PET. (15)O-H2O PET
      images were normalized and smoothed using SPM. A simplified reference tissue
      model with linear regression and spatial constraints was used to generate
      parametric DVR images. The DVR images were regressed on CBF images on a voxel-by
      voxel basis using robust biologic parametric mapping, adjusting for age and sex
      (false discovery rate, P = 0.05; spatial extent, 50 voxels). DVR images were also
      regressed on R1 images, a measure of the transport rate constant from vascular
      space to tissue. All analyses were performed on the entire sample, and on high
      and low tertiles of mean cortical DVR. RESULTS: Voxel-based analyses showed that
      increased DVR is associated with increased CBF in the frontal, parietal,
      temporal, and occipital cortices. However, this association appears to spare
      regions that typically show early Abeta deposition. A more robust relationship
      between DVR and CBF was observed in the lower tertile of DVR, that is, negligible
      cortical Abeta load, compared with the upper tertile of cortical DVR and Abeta
      load. The spatial distributions of the DVR-CBF and DVR-R1 correlations showed
      similar patterns. No reliable negative voxelwise relationships between DVR and
      CBF or R1 were observed. CONCLUSION: Robust associations between DVR and CBF at
      negligible Abeta levels, together with similar spatial distributions of DVR-CBF
      and DVR-R1 correlations, suggest that regional distribution of DVR reflects blood
      flow and tracer influx rather than pattern of Abeta deposition in those with
      minimal Abeta load. DVR-CBF associations in individuals with a higher DVR are
      more likely to reflect true associations between patterns of Abeta deposition and
      CBF or neural activity. These findings have important implications for analysis
      and interpretation of voxelwise correlations with external variables in
      individuals with varying amounts of Abeta load.

PMID- 25977463
TI  - 18F-FDG PET/CT for Therapy Control in Vascular Graft Infections: A First
      Feasibility Study.
AB  - The aim of this study was to evaluate the clinical value of PET/CT with (18)F-FDG
      for therapy control in patients with prosthetic vascular graft infections
      (PVGIs). METHODS: In this single-center, observational, prospective cohort study,
      25 patients with a median age of 66 y (range, 48-81 y) who had a proven PVGI were
      included. Follow-up (18)F-FDG PET/CT was performed at a median of 170 d (range,
      89-249 d) after baseline examination. Two independent and masked interpreters
      measured maximum standardized uptake values to quantify metabolic activity and
      analyzed whole-body datasets for a secondary diagnosis (i.e., infectious foci not
      near the graft). The metabolic activity of the graft was correlated with clinical
      information and 2 laboratory markers (C-reactive protein and white blood cell
      count). RESULTS: (18)F-FDG PET/CT had an impact on management in all patients. In
      19 of 25 patients (76%), antibiotic treatment was continued because of the
      results of follow-up (18)F-FDG PET/CT. Antibiotic treatment was stopped or
      changed in 8% and 16% of patients, respectively. In 8 patients (32%), additional
      incidental findings were detected on follow-up (18)F-FDG PET/CT and had a further
      impact on patient management. Only in a subgroup of patients with PVGI and no
      other sites of infection was a significant correlation found between the
      difference in C-reactive protein at the time of baseline and follow-up (18)F-FDG
      PET/CT and the difference in maximum standardized uptake value (n = 11; R(2) =
      0.67; P = 0.002). CONCLUSION: (18)F-FDG PET/CT represents a useful tool in
      therapy monitoring of PVGI and has an impact on patient management.

PMID- 25977465
TI  - PSMA PET in Prostate Cancer.

PMID- 25977464
TI  - Radiation Dosimetry of the Fibrin-Binding Probe 64Cu-FBP8 and Its Feasibility for
      PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in Rats.
AB  - The diagnosis of deep venous thromboembolic disease is still challenging despite
      the progress of current thrombus imaging modalities and new diagnostic
      algorithms. We recently reported the high target uptake and thrombus imaging
      efficacy of the novel fibrin-specific PET probe (64)Cu-FBP8. Here, we tested the
      feasibility of (64)Cu-FBP8 PET to detect source thrombi and culprit emboli after
      deep vein thrombosis and pulmonary embolism (DVT-PE). To support clinical
      translation of (64)Cu-FBP8, we performed a human dosimetry estimation using time
      dependent biodistribution in rats. METHODS: Sprague-Dawley rats (n = 7) underwent
      ferric chloride application on the femoral vein to trigger thrombosis. Pulmonary
      embolism was induced 30 min or 2 d after DVT by intrajugular injection of a
      preformed blood clot labeled with (125)I-fibrinogen. PET imaging was performed to
      detect the clots, and SPECT was used to confirm in vivo the location of the
      pulmonary emboli. Ex vivo gamma counting and histopathology were used to validate
      the imaging findings. Detailed biodistribution was performed in healthy rats (n =
      30) at different time points after (64)Cu-FBP8 administration to estimate human
      radiation dosimetry. Longitudinal whole-body PET/MR imaging (n = 2) was performed
      after (64)Cu-FBP8 administration to further assess radioactivity clearance.
      RESULTS: (64)Cu-FBP8 PET imaging detected the location of lung emboli and venous
      thrombi after DVT-PE, revealing significant differences in uptake between target
      and background tissues (P < 0.001). In vivo SPECT imaging and ex vivo gamma
      counting confirmed the location of the lung emboli. PET quantification of the
      venous thrombi revealed that probe uptake was greater in younger clots than in
      older ones, a result confirmed by ex vivo analyses (P < 0.001). Histopathology
      revealed an age-dependent reduction of thrombus fibrin content (P = 0.006),
      further supporting the imaging findings. Biodistribution and whole-body PET/MR
      imaging showed a rapid, primarily renal, body clearance of (64)Cu-FBP8. The
      effective dose was 0.021 mSv/MBq for males and 0.027 mSv/MBq for females,
      supporting the feasibility of using (64)Cu-FBP8 in human trials. CONCLUSION: We
      showed that (64)Cu-FBP8 PET is a feasible approach to image DVT-PE and that
      radiogenic adverse health effects should not limit the clinical translation of
      (64)Cu-FBP8.

PMID- 25977466
TI  - Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides:
      Potential of 18F-FDG PET Imaging in Ischemic Stroke Treatment.
AB  - Strategies to promote angiogenesis can benefit cerebral ischemia. We determined
      whether liposomal delivery of angiogenic peptides with a known biologic activity
      of vascular endothelial growth factor benefitted cerebral ischemia. Also, the
      study examined the potential of (18)F-FDG PET imaging in ischemic stroke
      treatment. METHODS: Male Sprague-Dawley rats (n = 40) underwent 40 min of middle
      cerebral artery occlusion. After 15 min of reperfusion, the rats (n = 10)
      received angiogenic peptides incorporated into liposomes. Animals receiving
      phosphate-buffered solution or liposomes without peptides served as controls. One
      week later, (18)F-FDG PET imaging was performed to examine regional changes in
      glucose utilization in response to the angiogenic therapy. The following day,
      (99m)Tc-hexamethylpropyleneamine oxime autoradiography was performed to determine
      changes in cerebral perfusion after angiogenic therapy. Corresponding changes in
      angiogenic markers, including von Willebrand factor and angiopoietin-1 and -2,
      were determined by immunostaining and polymerase chain reaction analysis,
      respectively. RESULTS: A 40-min period of middle cerebral artery occlusion
      decreased blood perfusion in the ipsilateral ischemic cortex of the brain,
      compared with that in the contralateral cortex, as measured by (99m)Tc
      hexamethylpropyleneamine oxime autoradiography. Liposomal delivery of angiogenic
      peptides to the ischemic hemisphere of the brain attenuated the cerebral
      perfusion defect compared with controls. Similarly, vascular density evidenced by
      von Willebrand factor-positive staining was increased in response to angiogenic
      therapy, compared with that of controls. This increase was accompanied by an
      early increase in angiopoietin-2 expression, a gene participating in
      angiogenesis. (18)F-FDG PET imaging measured at 7 d after treatment revealed that
      liposomal delivery of angiogenic peptides facilitated glucose utilization in the
      ipsilateral ischemic cortex of the brain, compared with that in the controls.
      Furthermore, the change in regional glucose utilization was correlated with the
      extent of improvement in cerebral perfusion (r = 0.742, P = 0.035). CONCLUSION:
      Liposomal delivery of angiogenic peptides benefits cerebral ischemia. (18)F-FDG
      PET imaging holds promise as an indicator of the effectiveness of angiogenic
      therapy in cerebral ischemia.

PMID- 25977468
TI  - Left atrial appendage closure: killing 2 birds with 1 stone?

PMID- 25977467
TI  - Repeatability of Radiotracer Uptake in Normal Abdominal Organs with 111In
      Pentetreotide Quantitative SPECT/CT.
AB  - With an increasing emphasis on quantitation of SPECT imaging and its use in
      dosimetry to guide therapies, it is desirable to understand the repeatability in
      normal-organ SPECT uptake values (SPECT-UVs). We investigated the variability of
      normal abdominal organ uptake in repeated (111)In-pentetreotide SPECT studies.
      METHODS: Nine patients with multiple (111)In-pentetreotide SPECT/CT studies for
      clinical purposes were evaluated. Volumes of interest were drawn for the
      abdominal organs and applied to SPECT-UVs. The variability of those values was
      assessed. RESULTS: The average SPECT-UV for the liver (1.7 +/- 0.6) was much
      lower than for the kidneys (right, 8.0 +/- 2.4; left, 7.5 +/- 1.7). Interpatient
      and intrapatient variability was similar (intraclass correlation coefficients,
      0.40-0.59) for all organs. The average coefficients of variation for each organ
      for each patient were obtained and averaged across all patients (0.26 for liver,
      0.22 for right kidney, and 0.20 for left kidney). The coefficients of variation
      for the organs across all scans were 0.33 (liver), 0.30 (right kidney), and 0.22
      (left kidney). CONCLUSION: Variability across all patients and all scans for the
      liver was higher than reported with (18)F-FDG PET, though left kidney variability
      was similar to PET liver variability and left kidney uptake may be able to serve
      as an internal metric for determining the quantifiability of an (111)In
      pentetreotide SPECT study.

PMID- 25977469
TI  - Left atrial appendage ligation in patients with atrial fibrillation leads to a
      decrease in atrial dispersion.
AB  - BACKGROUND: Left atrial appendage (LAA) exclusion has been performed in patients
      with atrial fibrillation (AF) to prevent thrombus formation and subsequent
      cardioembolic events. Left atrial electrical remodeling is a recognized factor in
      the recurrence of AF. The effects of LAA exclusion on P-wave characteristics and
      left atrial electrical remodeling have not been well described. The purpose of
      this study was to evaluate the effect of LAA ligation on P-wave morphology in
      patients with AF. METHODS AND RESULTS: Fifteen patients who were in sinus rhythm
      during the LAA ligation procedure were included in the study. We evaluated the P
      wave characteristics, including P-wave duration, P-wave amplitude, PQ interval,
      and P-wave dispersion, before and after ligation. Eleven patients had paroxysmal
      AF and 4 patients had persistent AF (12 male patients and 3 female patients). P
      wave duration immediately after ligation was significantly shorter compared with
      baseline in all limb leads except lead aVR (P<0.05). P-wave amplitude immediately
      after ligation was significantly greater compared with baseline in inferior
      leads; however, P-wave amplitude after 1 to 3 months was significantly lower
      compared with immediately after ligation. PQ interval immediately after ligation
      was significantly shorter compared with baseline (P=0.01), and P-wave dispersion
      after 1 to 3 months was significantly shorter compared with baseline (P=0.02).
      CONCLUSIONS: LAA exclusion produces consistent P-wave changes consistent with
      decreased atrial mass and decreased atrial dispersion that may represent reverse
      electrical atrial remodeling. This is a potential mechanism to explain the role
      of LAA ligation in maintaining sinus rhythm in patients with AF.

PMID- 25977470
TI  - Hydrogen Sulfide Levels and Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2)
      Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI).
AB  - BACKGROUND: Cystathionine gamma-lyase, cystathionine beta-synthase, and 3
      mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen
      sulfide (H2S). Functions of H2S are mediated by several targets including ion
      channels and signaling proteins. Nuclear factor-erythroid 2-related factor 2 is
      responsible for the expression of antioxidant response element-regulated genes
      and is known to be upregulated by H2S. We examined the levels of H2S, H2S
      producing enzymes, and nuclear factor-erythroid 2-related factor 2 activation
      status in skeletal muscle obtained from critical limb ischemia (CLI) patients.
      METHODS AND RESULTS: Gastrocnemius tissues were attained postamputation from
      human CLI and healthy control patients. We found mRNA and protein levels of
      cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate
      sulfurtransferase were significantly decreased in skeletal muscle of CLI patients
      as compared to control. H2S and sulfane sulfur levels were significantly
      decreased in skeletal muscle of CLI patients. We also observed significant
      reductions in nuclear factor-erythroid 2-related factor 2 activation as well as
      antioxidant proteins, such as Cu, Zn-superoxide dismutase, catalase, and
      glutathione peroxidase in skeletal muscle of CLI patients. Biomarkers of
      oxidative stress, such as malondialdehyde and protein carbonyl formation, were
      significantly increased in skeletal muscle of CLI patients as compared to healthy
      controls. CONCLUSIONS: The data demonstrate that H2S bioavailability and nuclear
      factor-erythroid 2-related factor 2 activation are both attenuated in CLI tissues
      concomitant with significantly increased oxidative stress. Reductions in the
      activity of H2S-producing enzymes may contribute to the pathogenesis of CLI.

PMID- 25977472
TI  - Allele Sharing and Evidence for Sexuality in a Mitochondrial Clade of Bdelloid
      Rotifers.
AB  - Rotifers of Class Bdelloidea are common freshwater invertebrates of ancient
      origin whose apparent asexuality has posed a challenge to the view that sexual
      reproduction is essential for long-term evolutionary success in eukaryotes and to
      hypotheses for the advantage of sex. The possibility nevertheless exists that
      bdelloids reproduce sexually under unknown or inadequately investigated
      conditions. Although certain methods of population genetics offer definitive
      means for detecting infrequent or atypical sex, they have not previously been
      applied to bdelloid rotifers. We conducted such a test with bdelloids belonging
      to a mitochondrial clade of Macrotrachela quadricornifera. This revealed a
      striking pattern of allele sharing consistent with sexual reproduction and with
      meiosis of an atypical sort, in which segregation occurs without requiring
      homologous chromosome pairs. 

PMID- 25977473
TI  - Negative feedback from CaSR signaling to aquaporin-2 sensitizes vasopressin to
      extracellular Ca2.
AB  - We previously described that high luminal Ca(2+) in the renal collecting duct
      attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through
      activation of the Ca(2+)-sensing receptor (CaSR). Here, we evaluated AQP2
      phosphorylation and permeability, in both renal HEK-293 cells and in the
      dissected inner medullary collecting duct, in response to specific activation of
      CaSR with NPS-R568. In CaSR-transfected cells, CaSR activation drastically
      reduced the basal levels of AQP2 phosphorylation at S256 (AQP2-pS256), thus
      having an opposite effect to vasopressin action. When forskolin stimulation was
      performed in the presence of NPS-R568, the increase in AQP2-pS256 and in the
      osmotic water permeability were prevented. In the freshly isolated inner mouse
      medullar collecting duct, stimulation with forskolin in the presence of NPS-R568
      prevented the increase in AQP2-pS256 and osmotic water permeability. Our data
      demonstrate that the activation of CaSR in the collecting duct prevents the cAMP
      dependent increase in AQP2-pS256 and water permeability, counteracting the short
      term vasopressin response. By extension, our results suggest the attractive
      concept that CaSR expressed in distinct nephron segments exerts a negative
      feedback on hormones acting through cAMP, conferring high sensitivity of hormone
      to extracellular Ca(2+). 

PMID- 25977471
TI  - Nonadditive Effects of Genes in Human Metabolomics.
AB  - Genome-wide association studies (GWAS) are widely applied to analyze the genetic
      effects on phenotypes. With the availability of high-throughput technologies for
      metabolite measurements, GWAS successfully identified loci that affect metabolite
      concentrations and underlying pathways. In most GWAS, the effect of each SNP on
      the phenotype is assumed to be additive. Other genetic models such as recessive,
      dominant, or overdominant were considered only by very few studies. In contrast
      to this, there are theories that emphasize the relevance of nonadditive effects
      as a consequence of physiologic mechanisms. This might be especially important
      for metabolites because these intermediate phenotypes are closer to the
      underlying pathways than other traits or diseases. In this study we analyzed
      systematically nonadditive effects on a large panel of serum metabolites and all
      possible ratios (22,801 total) in a population-based study [Cooperative Health
      Research in the Region of Augsburg (KORA) F4, N = 1,785]. We applied four
      different 1-degree-of-freedom (1-df) tests corresponding to an additive,
      dominant, recessive, and overdominant trait model as well as a genotypic model
      with two degree-of-freedom (2-df) that allows a more general consideration of
      genetic effects. Twenty-three loci were found to be genome-wide significantly
      associated (Bonferroni corrected P <= 2.19 * 10(-12)) with at least one
      metabolite or ratio. For five of them, we show the evidence of nonadditive
      effects. We replicated 17 loci, including 3 loci with nonadditive effects, in an
      independent study (TwinsUK, N = 846). In conclusion, we found that most genetic
      effects on metabolite concentrations and ratios were indeed additive, which
      verifies the practice of using the additive model for analyzing SNP effects on
      metabolites.

PMID- 25977474
TI  - A role for F-BAR protein Rga7p during cytokinesis in S. pombe.
AB  - F-BAR proteins are known to participate in cytokinesis, but their mechanisms are
      not well understood. Here we investigated Rga7p, an Schizosaccharomyces pombe F
      BAR protein with a RhoGAP domain. Localization of Rga7p to the cytokinetic
      cleavage furrow depends on its F-BAR domain, actin filaments, the formins Cdc12p
      and For3p, and the presence of a contractile ring. Rga7p is not required for the
      constriction of the contractile ring but does participate in the transport of a
      beta-glucan synthetase (Bgs4p) from the late Golgi compartments to plasma
      membrane that is adjacent to the contractile ring. Cells without Rga7p moved
      Bgs4p normally from the poles to the Golgi complex near to the cell center, but
      Bgs4p then moved slowly from the late Golgi compartments to the cleavage site.
      The late arrival and lower than normal numbers of Bgs4p result in septal defects
      late in cytokinesis, and in the lysis of separating cells, similar to that in
      cells with mutations in the cwg1(+) gene (which encodes Bgs4p). 

PMID- 25977475
TI  - Retrograde transport is not required for cytosolic translocation of the B-subunit
      of Shiga toxin.
AB  - Antigen-presenting cells have the remarkable capacity to transfer exogenous
      antigens to the cytosol for processing by proteasomes and subsequent presentation
      on major histocompatibility complex class-I (MHC-I) molecules, a process termed
      cross-presentation. This is the target of biomedical approaches that aim to
      trigger a therapeutic immune response. The receptor-binding B-subunit of Shiga
      toxin (STxB) has been developed as an antigen delivery tool for such
      immunotherapy applications. In this study, we have analyzed pathways and
      trafficking factors that are involved in this process. A covalent conjugate
      between STxB and saporin was generated to quantitatively sample the membrane
      translocation step to the cytosol in differentiated monocyte-derived THP-1 cells.
      We have found that retrograde trafficking to the Golgi complex was not required
      for STxB-saporin translocation to the cytosol or for STxB-dependent antigen cross
      presentation. Depletion of endosomal Rab7 inhibited, and lowering membrane
      cholesterol levels favored STxB-saporin translocation. Interestingly, experiments
      with reducible and non-reducible linker-arm-STxB conjugates led to the conclusion
      that after translocation, STxB remains associated with the cytosolic membrane
      leaflet. In summary, we report new facets of the endosomal escape process bearing
      relevance to antigen cross-presentation. 

PMID- 25977476
TI  - Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription
      and Girdin-Galphai3 signaling.
AB  - Epithelial apicobasal polarity has fundamental roles in epithelial physiology and
      morphogenesis. The PAR complex, comprising PAR-3, PAR-6 and atypical protein
      kinase C (aPKC), is involved in determining cell polarity in various biological
      contexts, including in epithelial cells. However, it is not fully understood how
      the PAR complex induces apicobasal polarity. In this study, we found that PAR-3
      regulates the protein expression of Girdin (also known as GIV or CCDC88A), a
      guanine-nucleotide-exchange factor (GEF) for heterotrimeric Galphai subunits, at
      the transcriptional level by cooperating with the AP-2 transcription factor. In
      addition, we confirmed that PAR-3 physically interacts with Girdin, and show that
      Girdin, together with the Galphai3 (also known as GNAI3), controls tight junction
      formation, apical domain development and actin organization downstream of PAR-3.
      Taken together, our findings suggest that transcriptional upregulation of Girdin
      expression and Girdin-Galphai3 signaling play crucial roles in regulating
      epithelial apicobasal polarity through the PAR complex. 

PMID- 25977477
TI  - CheckM: assessing the quality of microbial genomes recovered from isolates,
      single cells, and metagenomes.
AB  - Large-scale recovery of genomes from isolates, single cells, and metagenomic data
      has been made possible by advances in computational methods and substantial
      reductions in sequencing costs. Although this increasing breadth of draft genomes
      is providing key information regarding the evolutionary and functional diversity
      of microbial life, it has become impractical to finish all available reference
      genomes. Making robust biological inferences from draft genomes requires accurate
      estimates of their completeness and contamination. Current methods for assessing
      genome quality are ad hoc and generally make use of a limited number of "marker"
      genes conserved across all bacterial or archaeal genomes. Here we introduce
      CheckM, an automated method for assessing the quality of a genome using a broader
      set of marker genes specific to the position of a genome within a reference
      genome tree and information about the collocation of these genes. We demonstrate
      the effectiveness of CheckM using synthetic data and a wide range of isolate-,
      single-cell-, and metagenome-derived genomes. CheckM is shown to provide accurate
      estimates of genome completeness and contamination and to outperform existing
      approaches. Using CheckM, we identify a diverse range of errors currently
      impacting publicly available isolate genomes and demonstrate that genomes
      obtained from single cells and metagenomic data vary substantially in quality. In
      order to facilitate the use of draft genomes, we propose an objective measure of
      genome quality that can be used to select genomes suitable for specific gene- and
      genome-centric analyses of microbial communities. 

PMID- 25977479
TI  - Neuroradiologic Diagnosis of Minor Leak prior to Major SAH: Diagnosis by T1-FLAIR
      Mismatch.
AB  - BACKGROUND AND PURPOSE: In major SAH, the only method to diagnose a preceding
      minor leak is to ascertain the presence of a warning headache by interview;
      however, poor clinical condition and recall bias can cause inaccuracy. We devised
      a neuroradiologic method to diagnose previous minor leak in patients with SAH and
      attempted to determine whether warning (sentinel) headaches were associated with
      minor leaks before major SAH. MATERIALS AND METHODS: We retrospectively evaluated
      127 patients who were admitted with SAH within 48 hours of ictus. Previous minor
      leak before major SAH was defined as T1WI-detected clearly bright hyperintense
      subarachnoid blood accompanied by SAH blood on FLAIR images that was distributed
      over a larger area than bright hyperintense subarachnoid blood on T1WI (T1-FLAIR
      mismatch). RESULTS: The incidence of warning headache before SAH was 11.0% (14 of
      127 patients, determined by interview). The incidence of T1-FLAIR mismatch
      (neuroradiologic diagnosis of minor leak before major SAH) was 33.9% (43 of 127
      patients). Of the 14 patients with warning headache, 13 had a minor leak
      diagnosed by T1-FLAIR mismatch at the time of admission. Variables identified by
      multivariate analysis as significantly associated with minor leak diagnosed by T1
      FLAIR mismatch included 80 years of age or older, rebleeding after admission,
      intracerebral hemorrhage on CT, and mRS scores of 3-6. CONCLUSIONS: We conclude
      that warning headaches diagnosed by interview are not a product of recall bias
      but are the result of actual leaks from aneurysms.

PMID- 25977478
TI  - Evaluating CT Perfusion Deficits in Global Cerebral Edema after Aneurysmal
      Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Global cerebral edema is an independent predictor of
      mortality and poor outcomes after aneurysmal SAH. Global cerebral edema, a
      complex disease process, is thought to be associated with an altered cerebral
      autoregulatory response. We studied the association between cerebral hemodynamics
      and early global cerebral edema by using CTP. MATERIALS AND METHODS: We
      retrospectively studied consecutive patients with aneurysmal SAH with admission
      CTP performed at days 0-3. Two neuroradiologists classified global cerebral edema
      and hydrocephalus on NCCT performed concurrently with CTP. Global cerebral edema
      was defined as diffuse effacement of the sulci and/or basal cisterns or diffuse
      disruption of the cerebral gray-white matter junction. CTP was postprocessed into
      CBF and MTT maps by using a standardized method. Quantitative analysis of CTP was
      performed by using standard protocol with ROI sampling of the cerebral cortex.
      The Fisher exact test, Mann-Whitney test, and independent-samples t test were
      used to determine statistical associations. RESULTS: Of the 45 patients included,
      42% (19/45) had global cerebral edema and 58% (26/45) did not. Patient groups
      with and without global cerebral edema were well-matched for demographic and
      clinical data. Patients with global cerebral edema were more likely to have
      qualitative global CTP deficits than those without global cerebral edema (P =
      .001) with an OR = 13.3 (95% CI, 2.09-138.63). Patients with global cerebral
      edema also had a very strong trend toward statistical significance, with reduced
      quantitative CBF compared with patients without global cerebral edema (P = .064).
      CONCLUSIONS: Global perfusion deficits are significantly associated with global
      cerebral edema in the early phase after aneurysmal SAH, supporting the theory
      that hemodynamic disturbances occur in global cerebral edema.

PMID- 25977480
TI  - Aqueductal Stroke Volume: Comparisons with Intracranial Pressure Scores in
      Idiopathic Normal Pressure Hydrocephalus.
AB  - BACKGROUND AND PURPOSE: Aqueductal stroke volume from phase-contrast MR imaging
      has been proposed for predicting shunt response in normal pressure hydrocephalus.
      However, this biomarker has remained controversial in use and has a lack of
      validation with invasive intracranial monitoring. We studied how aqueductal
      stroke volume compares with intracranial pressure scores in the presurgical work
      up and clinical score, ventricular volume, and aqueduct area and assessed the
      patient's response to shunting. MATERIALS AND METHODS: Phase-contrast MR imaging
      was performed in 21 patients with probable idiopathic normal pressure
      hydrocephalus. Patients were selected for shunting on the basis of pathologically
      increased intracranial pressure pulsatility. Patients with shunts were offered a
      second MR imaging after 12 months. Ventricular volume and transverse aqueductal
      area were calculated, as well as clinical symptom score. RESULTS: No correlations
      between aqueductal stroke volume and preoperative scores of mean intracranial
      pressure or mean wave amplitudes were observed. Preoperative aqueductal stroke
      volume was not different between patients with shunts and conservatively treated
      patients (P = .69) but was correlated with ventricular volume (R = 0.60, P =
      .004) and aqueductal area (R = 0.58, P = .006) but not with the severity or
      duration of clinical symptoms. After shunting, aqueductal stroke volume (P =
      .006) and ventricular volume (P = .002) were reduced. A clinical improvement was
      seen in 16 of 17 patients who had shunts (94%). CONCLUSIONS: Aqueductal stroke
      volume does not reflect intracranial pressure pulsatility or symptom score, but
      rather aqueduct area and ventricular volume. The results do not support the use
      of aqueductal stroke volume for selecting patients for shunting.

PMID- 25977481
TI  - Mean Diffusional Kurtosis in Patients with Glioma: Initial Results with a Fast
      Imaging Method in a Clinical Setting.
AB  - BACKGROUND AND PURPOSE: Diffusional kurtosis imaging is an MR imaging technique
      that provides microstructural information in biologic systems. Its application in
      clinical studies, however, is hampered by long acquisition and postprocessing
      times. We evaluated a new and fast (2 minutes 46 seconds) diffusional kurtosis
      imaging method with regard to glioma grading, compared it with conventional
      diffusional kurtosis imaging, and compared the diagnostic accuracy of fast mean
      kurtosis (MK') to that of the widely used mean diffusivity. MATERIALS AND
      METHODS: MK' and mean diffusivity were measured in the contrast-enhancing tumor
      core, the perifocal hyperintensity (indicated on T2 FLAIR images), and the
      contralateral normal-appearing white and gray matter of 34 patients (22 with high
      grade and 12 with low-grade gliomas). MK' and mean diffusivity in the different
      tumor grades were compared by using a Wilcoxon rank sum test. Receiver operating
      characteristic curves and the areas under the curve were calculated to determine
      the diagnostic accuracy of MK' and mean diffusivity. RESULTS: MK' in the tumor
      core, but not mean diffusivity, differentiated high-grade from low-grade gliomas,
      and MK' differentiated glioblastomas from the remaining gliomas with high
      accuracy (area under the curveMK' = 0.842; PMK' < .001). MK' and mean diffusivity
      identified glioblastomas in the group of high-grade gliomas with similar
      significance and accuracy (area under the curveMK' = 0.886; area under the
      curvemean diffusivity = 0.876; PMK' = .003; Pmean diffusivity = .004). The mean
      MK' in all tissue types was comparable to that obtained by conventional
      diffusional kurtosis imaging. CONCLUSIONS: The diffusional kurtosis imaging
      approach used here is considerably faster than conventional diffusional kurtosis
      imaging methods but yields comparable results. It can be accommodated in clinical
      protocols and enables exploration of the role of MK' as a biomarker in
      determining glioma subtypes or response evaluation.

PMID- 25977482
TI  - Hyperintense Vessels on FLAIR: Hemodynamic Correlates and Response to
      Thrombolysis.
AB  - BACKGROUND AND PURPOSE: Hyperintense vessels on baseline FLAIR MR imaging of
      patients with ischemic stroke have been linked to leptomeningeal
      collateralization, yet the ability of these to maintain viable ischemic tissue
      remains unclear. We investigated whether hyperintense vessels on FLAIR are
      associated with the severity of hypoperfusion and response to thrombolysis in
      patients treated with intravenous tissue-plasminogen activator. MATERIALS AND
      METHODS: Consecutive patients with ischemic stroke with an MR imaging before and
      within 24 hours of treatment, with proved vessel occlusion and available time-to
      maximum maps were included (n = 62). The severity of hypoperfusion was
      characterized on the basis of the hypoperfusion intensity ratio (volume with
      severe/mild hypoperfusion [time-to-maximum >= 8 seconds / time-to-maximum >= 2
      seconds]). The hypoperfusion intensity ratio was dichotomized at the median to
      differentiate moderate (hypoperfusion intensity ratio <= 0.447) and severe
      (hypoperfusion intensity ratio > 0.447) hypoperfusion. Good outcome was defined
      as a modified Rankin Scale score of <=2. RESULTS: Hyperintense vessels on FLAIR
      were identified in 54 patients (87%). Patients with extensive hyperintense
      vessels on FLAIR (>4 sections) had higher NIHSS scores, larger baseline lesion
      volumes, higher rates of perfusion-diffusion mismatch, and more severe
      hypoperfusion (hypoperfusion intensity ratio). In stepwise backward multivariate
      regression analysis for the dichotomized hypoperfusion intensity ratio (including
      stroke etiology, age, perfusion deficit, baseline lesion volume, smoking, and
      extent of hyperintense vessels on FLAIR), extensive hyperintense vessels on FLAIR
      were independently associated with severe hypoperfusion (OR, 6.8; 95% CI, 1.1
      42.7; P = .04). The hypoperfusion intensity ratio was an independent predictor of
      a worse functional outcome at 3 months poststroke (OR, 0.2; 95% CI, 0.5-0.6; P <
      .01). CONCLUSIONS: Hyperintense vessels on FLAIR are associated with larger
      perfusion deficits, larger infarct growth, and more severe hypoperfusion,
      suggesting that hyperintense vessels on FLAIR most likely indicate severe
      ischemia as a result of insufficient collateralization.

PMID- 25977483
TI  - ATP-sensitive potassium channel activation induces angiogenesis in vitro and in
      vivo.
AB  - Intense research is conducted to identify new molecular mechanisms of
      angiogenesis. Previous studies have shown that the angiogenic effects of hydrogen
      sulfide (H2S) depend on the activation of ATP-sensitive potassium channels (KATP)
      and that C-type natriuretic peptide (CNP), which can act through KATP, promotes
      endothelial cell growth. We therefore investigated whether direct KATP activation
      induces angiogenic responses and whether it is required for the endothelial
      responses to CNP or vascular endothelial growth factor (VEGF). Chick
      chorioallantoic membrane (CAM) angiogenesis was similarly enhanced by the direct
      KATP channel activator 2-nicotinamidoethyl acetate (SG-209) and by CNP or VEGF.
      The KATP inhibitors glibenclamide and 5-hydroxydecanoate (5-HD) reduced basal and
      abolished CNP-induced CAM angiogenesis. In vitro, the direct KATP openers
      nicorandil and SG-209 and the polypeptides VEGF and CNP increased proliferation
      and migration in bEnd.3 mouse endothelial cells. In addition, VEGF and CNP
      induced cord-like formation on Matrigel by human umbilical vein endothelial cells
      (HUVECs). All these in vitro endothelial responses were effectively abrogated by
      glibenclamide or 5-HD. In HUVECs, a small-interfering RNA-mediated decrease in
      the expression of the inwardly rectifying potassium channel (Kir) 6.1 subunit
      impaired cell migration and network morphogenesis in response to either SG-209 or
      CNP. We conclude that 1) direct pharmacologic activation of KATP induces
      angiogenic effects in vitro and in vivo, 2) angiogenic responses to CNP and VEGF
      depend on KATP activation and require the expression of the Kir6.1 KATP subunit,
      and 3) KATP activation may underpin angiogenesis to a variety of vasoactive
      stimuli, including H2S, VEGF, and CNP. 

PMID- 25977485
TI  - Highly pathogenic avian influenza spreads in the USA.

PMID- 25977486
TI  - Canine leishmaniosis: assessing the situation in Europe.

PMID- 25977487
TI  - Food group cuts 'critically important' antibiotics from poultry production.

PMID- 25977488
TI  - Matching the right dog to the right home.
AB  - Many people want to own a dog but - with more than 200 registered breeds with
      different characteristics and requirements to choose from - they need to find the
      right one for them. Georgina Mills reports on a discussion of how potential
      owners can be helped to make the right choices, which took place during the
      recent BSAVA congress in Birmingham.

PMID- 25977489
TI  - Animal medicines: consumers 'more confused than ever', says NOAH.

PMID- 25977491
TI  - Ethylene glycol poisoning in sheep.
AB  - Oxalate toxicity in sheep as a consequence of exposure to ethylene glycol.
      Chlamydophila abortus infection in a dairy cow. Neosporosis diagnosed in a
      newborn lamb with deformities. Yersiniosis affecting a 1000-strong goat herd.
      Porcine reproductive and respiratory syndrome causing blue ears in 14-week-old
      pigs. Avian tuberculosis diagnosed in an adult Mandarin duck. These are among
      matters discussed in the Animal and Plant Health Agency's (APHA's) disease
      surveillance report for January and February 2015.

PMID- 25977492
TI  - Tackling lameness in sheep and evaluating progress.

PMID- 25977493
TI  - Alternative dispute resolution trial.

PMID- 25977494
TI  - Alternative dispute resolution trial.

PMID- 25977495
TI  - Equality and diversity.

PMID- 25977496
TI  - Bovine TB in the pilot badger cull zone in Gloucestershire.

PMID- 25977498
TI  - Applying knowledge, facing challenges.
AB  - After qualifying from Cambridge, Greg Dickens looked for a job that could support
      him while he tried to break into international sport. He became an innovation
      consultant, inventing or modifying new technologies, for which, he says, the
      skills developed during the veterinary degree are ideal. 

PMID- 25977499
TI  - Diary of a poultry intern.
AB  - In his post as poultry intern, William Garton is finding that CPD takes up a
      large proportion of his time. This, he says, can be quite enjoyable, particularly
      when events are sponsored by international pharmaceutical companies. This month,
      he has been on two training courses, one in Spain and the other in Belgium. 

PMID- 25977500
TI  - Widmark calculations and their uncertainty.

PMID- 25977508
TI  - Erratum.

PMID- 25977501
TI  - Response to Letter to the editor.

PMID- 25977509
TI  - A bioassay to measure energy metabolism in mouse colonic crypts, organoids, and
      sorted stem cells.
AB  - Evidence suggests that targeting cancer cell energy metabolism might be an
      effective therapeutic approach for selective ablation of malignancies. Using a
      Seahorse Extracellular Flux Analyzer, we have demonstrated that select
      environmental agents can alter colonic mitochondrial function by increasing
      respiration-induced proton leak, thereby inducing apoptosis, a marker of colon
      cancer risk. To further probe bioenergetics in primary intestinal cells, we
      developed methodology that can be modified and adapted to measure the
      bioenergetic profiles of colonic crypts, the basic functional unit of the colon,
      and colonic organoids, an ex vivo 3D culture of colonic crypts. Furthermore, in
      combination with the MoFlo Astrios High-Speed Cell Sorter, we were able to
      measure the bioenergetic profiles of colonic adult stem and daughter cells from
      Lgr5-EGFP-IRES-creER(T2) transgenic mice. We examined the effects of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a full arylhydrocarbon receptor agonist,
      known to affect gastrointestinal function and cancer risk, on the bioenergetic
      profiles of intestinal epithelial cells. Mouse colonic crypts, organoids, or
      sorted single cells were seeded onto Matrigel-precoated Seahorse XF24 microplates
      for extracellular flux analysis. Temporal analyses revealed distinct energy
      metabolic profiles in crypts and organoids challenged with TCDD. Furthermore,
      sorted Lgr5(+) stem cells exhibited a Warburg-like metabolic profile. This is
      noteworthy because perturbations in stem cell dynamics are generally believed to
      represent the earliest step toward colon tumorigenesis. We propose that our
      innovative methodology may facilitate future in vivo/ex vivo metabolic studies
      using environmental agents affecting colonocyte energy metabolism. 

PMID- 25977511
TI  - Deceleration of liver regeneration by knockdown of augmenter of liver
      regeneration gene is associated with impairment of mitochondrial DNA synthesis in
      mice.
AB  - Hepatic stimulator substance, also known as augmenter of liver regeneration
      (ALR), is a novel hepatic mitogen that stimulates liver regeneration after
      partial hepatectomy (PH). Recent work has indicated that a lack of ALR expression
      inhibited liver regeneration in rats, and the mechanism seems to be related to
      increased cell apoptosis. The mitochondria play an important role during liver
      regeneration. Adequate ATP supply, which is largely dependent on effective
      mitochondrial biogenesis, is essential for progress of liver regeneration.
      However, ALR gene expression during liver regeneration, particularly its function
      with mitochondrial DNA synthesis, remains poorly understood. In this study, ALR
      expression in hepatocytes of mice was suppressed with ALR short-hairpin RNA
      interference or ALR deletion (knockout, KO). The ALR-defective mice underwent PH,
      and the liver was allowed to regenerate for 1 wk. Analysis of liver growth and
      its correlation with mitochondrial biogenesis showed that both ALR mRNA and
      protein levels increased robustly in control mice with a maximum at days 3 and 4
      post-PH. However, ALR knockdown inhibited hepatic DNA synthesis and decelerated
      liver regeneration after PH. Furthermore, both in the ALR-knockdown and ALR-KO
      mice, expression of mitochondrial transcription factor A and peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha were reduced, resulting
      in impaired mitochondrial biogenesis. In conclusion, ALR is apparently required
      to ensure appropriate liver regeneration following PH in mice, and deletion of
      the ALR gene may delay liver regeneration in part due to impaired mitochondrial
      biogenesis. 

PMID- 25977510
TI  - Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in
      gastric epithelial cell migration.
AB  - The pyloric antral hormone gastrin plays a role in remodeling of the gastric
      epithelium, but the specific targets of gastrin that mediate these effects are
      poorly understood. Glandular epithelial cells of the gastric corpus express
      matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue
      remodeling; some of these cells express the CCK-2 receptor at which gastrin acts.
      We have now examined the hypothesis that gastrin stimulates expression of MMP-1
      in the stomach. We determined MMP-1 transcript abundance in gastric mucosal
      biopsies from Helicobacter pylori negative human subjects with normal gastric
      mucosal histology, who had a range of serum gastrin concentrations due in part to
      treatment with proton pump inhibitors (PPI). The effects of gastrin were studied
      on gastric epithelial AGS-GR cells using Western blot and migration assays. In
      human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript
      abundance was increased 2-fold; there was also increased MMP-7 transcript
      abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance,
      as well that of a minor band corresponding to active MMP-1, in the media of AGS
      GR cells, and the response was mediated by protein kinase C and p42/44 MAP
      kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR
      cell migration in both scratch wound and Boyden chamber assays was inhibited by
      MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of
      gastrin implicated in mucosal remodeling. 

PMID- 25977512
TI  - Results of Provider and Consumer Survey on Nutrition Therapy Insurance Coverage.

PMID- 25977513
TI  - Nutrition Considerations in Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a serious degenerative muscular disease
      affecting males. Diagnosis usually occurs in childhood and is confirmed through
      genetic testing and/or muscle biopsy. Accompanying the disease are several
      nutrition-related concerns: growth, body composition, energy and protein
      requirements, constipation, swallowing difficulties, bone health, and
      complementary medicine. This review article addresses the nutrition aspects of
      DMD. 

PMID- 25977514
TI  - Editorial: a lasting impact.

PMID- 25977517
TI  - Mapping epidemiology's past to inform its future: metaknowledge analysis of
      epidemiologic topics in leading journals, 1974-2013.
AB  - An empiric perspective on what epidemiology has studied over time might inform
      discussions about future directions for the discipline. We aimed to identify the
      main areas of epidemiologic inquiry and determine how they evolved over time in 5
      high-impact epidemiologic journals. We analyzed the titles and abstracts of
      20,895 articles that were published between 1974 and 2013. In 5 time periods that
      reflected approximately equal numbers of articles, we identified the main topics
      by clustering terms based on co-occurrence. Infectious disease and cardiovascular
      disease epidemiology were the prevailing topics over the 5 periods. Cancer
      epidemiology was a major topic from 1974 to 2001 but disappeared thereafter.
      Nutritional epidemiology gained relative importance from 1974 to 2013.
      Environmental epidemiology appeared during 1996-2001 and continued to be
      important, whereas 2 clusters related to methodology and meta-analysis in
      genetics appeared during 2008-2013. Several areas of epidemiology, including
      injury or psychiatric epidemiology, did not make an appearance as major topics at
      any time. In an ancillary analysis of 6 high-impact general medicine journals, we
      found patterns of epidemiologic articles that were overall consistent with the
      findings in epidemiologic journals. This metaknowledge investigation allowed
      identification of the dominant topics in and conversely those that were absent
      from 5 major epidemiologic journals. We discuss implications for the field. 

PMID- 25977515
TI  - Body mass index in young adulthood, obesity trajectory, and premature mortality.
AB  - Although much research has been conducted on the role adult body mass index (BMI)
      plays in mortality, there have been fewer studies that evaluated the associations
      of BMI in young adulthood and adult weight trajectory with mortality, and it
      remains uncertain whether associations differ by race or sex. We prospectively
      examined the relationships of BMI in young adulthood (21 years of age) and adult
      obesity trajectory with later-life mortality rates among 75,881 men and women in
      the Southern Community Cohort Study. Study participants were enrolled between
      2002 and 2009 at ages 40-79 years and were followed through December, 2011.
      Multivariable Cox proportional hazards models were used to estimate hazard ratios
      and 95% confidence intervals. There were 7,301 deaths in the 474,970 person-years
      of follow-up. Participants who reported being overweight or obese as young adults
      had mortality rates that were 19% (95% confidence interval: 12, 27) and 64% (95%
      confidence interval: 52, 78) higher, respectively, than those of their normal
      weight counterparts. The results did not significantly differ by race or sex.
      Participants who reported being obese in young adulthood only or in both young
      and middle adulthood experienced mortality rates that were 40%-90% higher than
      those of participants who were nonobese at either time. These results suggest
      that obesity in young adulthood is associated with higher mortality risk
      regardless of race, sex, and obesity status in later life. 

PMID- 25977518
TI  - Clinical group supervision for integrating ethical reasoning: Views from students
      and supervisors.
AB  - BACKGROUND: Clinical group supervision has existed for over 20 years in nursing.
      However, there is a lack of studies about the role of supervision in nursing
      students' education and especially the focus on ethical reasoning. AIM: The aim
      of this study was to explore and describe nursing students' ethical reasoning and
      their supervisors' experiences related to participation in clinical group
      supervision. RESEARCH DESIGN: The study is a qualitative interview study with
      interpretative description as an analysis approach. PARTICIPANTS AND RESEARCH
      CONTEXT: A total of 17 interviews were conducted with nursing students (n = 12)
      who had participated in clinical group supervision in their first year of nursing
      education, and with their supervisors (n = 5). ETHICAL CONSIDERATIONS: The study
      was based on the ethical principles outlined in the Declaration of Helsinki, and
      permission was obtained from the Regional Ethical Review Board in Sweden.
      FINDINGS: The analysis revealed that both the form and content of clinical group
      supervision stimulated reflection and discussion of handling of situations with
      ethical aspects. Unethical situations were identified, and the process uncovered
      underlying caring actions. DISCUSSION AND CONCLUSION: Clinical group supervision
      is a model that can be used in nursing education to train ethical reflection and
      to develop an ethical competence among nursing students. Outcomes from the model
      could also improve nursing education itself, as well as healthcare organizations,
      in terms of reducing moral blindness and unethical nursing practice.

PMID- 25977519
TI  - The moral courage of nursing students who complete advance directives with
      homeless persons.
AB  - BACKGROUND: Homeless persons in the United States have disproportionately high
      rates of illness, injury, and mortality and tend to believe that the quality of
      their end-of-life care will be poor. No studies were found as to whether nurses
      or nursing students require moral courage to help homeless persons or members of
      any other demographic complete advance directives. RESEARCH HYPOTHESIS: We
      hypothesized that baccalaureate nursing students require moral courage to help
      homeless persons complete advance directives. Moral courage was defined as a
      trait of a person or an action that overcomes fears or other challenges to
      achieve something of great moral worth. RESEARCH DESIGN: The hypothesis was
      investigated through a qualitative descriptive study. Aside from the pre
      selection of a single variable to study (i.e. moral courage), our investigation
      was a naturalistic inquiry with narrative hues insofar as it attended to specific
      words and phrases in the data that were associated with that variable.
      PARTICIPANTS AND RESEARCH CONTEXT: A total of 15 baccalaureate nursing students
      at a public university in the United States responded to questionnaires that
      sought to elicit fears and other challenges that they both expected to experience
      and actually experienced while helping homeless persons complete advance
      directives at a local, non-profit service agency. ETHICAL CONSIDERATIONS: The
      study was approved by the Internal Review Board of the authors' university, and
      each participant signed an informed consent form, which stated that the study
      involved no reasonably foreseeable risks and that participation was voluntary.
      FINDINGS: Before meeting with homeless persons, participants reported that they
      expected to experience two fears and a challenge: fear of behaving in ways that a
      homeless person would deem inappropriate, fear of discussing a homeless person's
      dying and death, and the challenge of adequately conveying the advance
      directive's meaning and accurately recording a homeless person's end-of-life
      wishes. In contrast, after their meetings with homeless persons, relatively few
      participants reported having encountered those obstacles. So, while participants
      required moral courage to assist homeless persons with advance directives, they
      required greater moral courage as they anticipated their meetings than during
      those meetings. DISCUSSION: Our study breaks new ground at the intersection of
      nursing, moral courage, and advance directives. It might also have important
      implications for how to improve the training that US nursing students receive
      before they provide this service. CONCLUSION: Our results cannot be generalized,
      but portions of our approach are likely to be transferable to similar social
      contexts. For example, because homeless persons are misunderstood and
      marginalized throughout the United States, our design for training nursing
      students to provide this service is also likely to be useful across the United
      States. Internationally, however, it is not yet known whether our participants'
      fears and the challenge they faced are also experienced by those who assist
      homeless persons or members of other vulnerable populations in documenting
      healthcare wishes.

PMID- 25977516
TI  - Association of Sleep Apnea and Snoring With Incident Atrial Fibrillation in the
      Multi-Ethnic Study of Atherosclerosis.
AB  - The association between sleep apnea and atrial fibrillation (AF) has not been
      examined in a multiethnic adult population in prospective community-based
      studies. We prospectively (2000-2011) investigated the associations of physician
      diagnosed sleep apnea (PDSA), which is considered more severe sleep apnea, and
      self-reported habitual snoring without PDSA (HS), a surrogate for mild sleep
      apnea, with incident AF in white, black, and Hispanic participants in the Multi
      Ethnic Study of Atherosclerosis (MESA) who were free of clinical cardiovascular
      disease at baseline (2000-2002). Cox proportional hazards models were used to
      assess the associations, with adjustment for socioeconomic status, traditional
      vascular disease risk factors, race/ethnicity, body mass index, diabetes, chronic
      kidney disease, alcohol intake, and lipid-lowering therapy. Out of 4,395
      respondents to a sleep questionnaire administered in MESA, 181 reported PDSA,
      1,086 reported HS, and 3,128 reported neither HS nor PDSA (unaffected). Over an
      average 8.5-year follow-up period, 212 AF events were identified. As compared
      with unaffected participants, PDSA was associated with incident AF in the
      multivariable analysis, but HS was not (PDSA: hazard ratio = 1.76, 95% confidence
      interval: 1.03, 3.02; HS: hazard ratio = 1.02, 95% confidence interval: 0.72,
      1.44). PDSA, a marker of more severe sleep apnea, was associated with higher risk
      of incident AF in this analysis of MESA data. 

PMID- 25977520
TI  - Ethical challenges: Trust and leadership in dementia care.
AB  - INTRODUCTION: To meet and take care of people with dementia implicate
      professional and moral challenges for caregivers. Using force happens daily.
      However, staff also encounter challenges with the management in the units.
      Managing the caretaking function is also significant in how caretakers experience
      working in dementia care. PURPOSE: The purpose of this study is to explore the
      caregiver's experiences with ethical challenges in dementia care settings and the
      significance of professional leadership in this context. METHOD: The design is
      qualitative, and data appear through narrative interviews. A total of 23
      caretakers participated in the study. The transcribed interviews were subjected
      to a phenomenological-hermeneutical interpretation. ETHICAL CONSIDERATIONS: The
      respondents signed an informed consent for participation prior to the interviews.
      They were assured anonymity and confidentiality in the publication of the data.
      Ricoeur's method for interpretation ensures anonymity as the researcher relates
      to the data as one collective text. The study is part of a larger research
      project in ethics, in its entirety approved in line with the Helsinki Convention.
      RESULTS: The findings show that the caretakers experienced inadequacy. Some of
      them described a negative work atmosphere where they experienced that their
      leaders did not take them seriously. Because of this, informal negative sub
      groups functioned as an exclusive debriefing arena. Some of the informants
      described the opposite experience where the leaders actively supported them.
      DISCUSSION: The analyses of the findings are discussed in light of the concepts
      of trust and mistrust in leadership. CONCLUSION: There is a correlation between
      the leadership and the caregivers' experience of being in difficult situations.

PMID- 25977521
TI  - Ethical aspects of caregivers' experience with persons with dementia at
      mealtimes.
AB  - BACKGROUND: Persons with dementia are at risk of malnutrition and thus in need of
      assistance during mealtimes. Research suggest interventions for caregivers to
      learn how to facilitate mealtimes and eating, while other suggest a working
      environment enabling the encounter needed to provide high-quality care. However,
      the phenomenon of caring for this unique population needs to be elucidated from
      several perspectives before suggesting suitable implications that ensure their
      optimal health. OBJECTIVES: To illustrate the meanings within caregivers'
      experiences of caring for persons with dementia during mealtime situations. We
      also measured weight and food intake among individuals with dementia to explain
      better the phenomenon of caring for them during mealtimes. METHODS: Mixed method
      including focus group interviews with seven caregivers analyzed using
      phenomenological hermeneutics. In addition, for nine persons with dementia,
      weight and food intake were collected and descriptive statistics were calculated.
      ETHICAL CONSIDERATIONS: Ethical review was obtained from an ethics committee, and
      all caregivers signed a consent form after being informed on the issue of
      research ethics. Relatives for persons with dementia were informed and signed the
      consent. In addition, throughout the study, the persons' expressions were
      observed aiming to respect their vulnerability, integrity, and dignity. FINDINGS:
      One theme emerged from interviews (struggling between having the knowledge and
      not the opportunity), which was built upon three subthemes (being engaged and
      trying; feeling abandoned and insufficient; being concerned and feeling guilty).
      Seven of nine persons with dementia lost a minimum of 1.3 kg of weight and ate a
      maximum of 49.7% of the food served. CONCLUSION: Caregivers struggle because they
      have knowledge about how to provide high-quality care but are unable to provide
      this care due to organizational structures. The weight loss and insufficient
      eating among the persons with dementia may support this conclusion. Sufficient
      time for adequate care should be provided.

PMID- 25977522
TI  - Diagnosis of Acute Groin Injuries: A Prospective Study of 110 Athletes.
AB  - BACKGROUND: Acute groin injuries are common in high-intensity sports, but there
      are insufficient data on injury characteristics such as injury mechanisms and
      clinical and radiological findings. PURPOSE: To describe these characteristics in
      a cohort of athletes. STUDY DESIGN: Cross-sectional study; Level of evidence, 3.
      METHODS: A total of 110 male athletes (mean age, 25.6 +/- 4.7 years) with sports
      related acute groin pain were prospectively included within 7 days of injury from
      August 2012 to April 2014. Standardized history taking, a clinical examination,
      magnetic resonance imaging (MRI), and/or ultrasound (US) were performed. RESULTS:
      The most frequent injury mechanism in soccer was kicking (40%), and change of
      direction was most frequent in other sports (31%). Clinically, adductor injuries
      accounted for 66% of all injuries and primarily involved the adductor longus on
      imaging (91% US, 93% MRI). The iliopsoas and proximal rectus femoris were also
      frequently injured according to all examination modalities (15%-25%). Acute
      injury findings were negative in 22% of the MRI and 25% of the US examinations.
      Of the clinically diagnosed adductor injuries, 3% (US) and 6% (MRI) showed a
      radiological injury in a different location compared with 35% to 46% for
      clinically diagnosed iliopsoas and proximal rectus femoris injuries. CONCLUSION:
      Adductor injuries account for the majority of acute groin injuries. Iliopsoas and
      proximal rectus femoris injuries are also common. More than 1 in 5 injuries
      showed no imaging signs of an acute injury. Clinically diagnosed adductor
      injuries were often confirmed on imaging, whereas iliopsoas and rectus femoris
      injuries showed a different radiological injury location in more than one-third
      of the cases. The discrepancy between clinical and radiological findings should
      be considered when diagnosing acute groin injuries.

PMID- 25977523
TI  - Proportion of Patients Reporting Acceptable Symptoms or Treatment Failure and
      Their Associated KOOS Values at 6 to 24 Months After Anterior Cruciate Ligament
      Reconstruction: A Study From the Norwegian Knee Ligament Registry.
AB  - BACKGROUND: The proportion of patients perceiving their symptoms as either
      acceptable or as a failure of treatment after anterior cruciate ligament
      reconstruction (ACLR) is unknown. Commonly used outcome scores such as the Knee
      injury and Osteoarthritis Outcome Score (KOOS) suffer from poor interpretability,
      and little is known about which scores represent an acceptable or failed
      postoperative outcome. PURPOSE: To determine the proportion of patients reporting
      acceptable symptoms or treatment failure at 6 to 24 months after ACLR and to
      define KOOS values corresponding to the patients' perceptions of treatment
      outcome. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: In
      2012, a total of 1197 patients were randomly extracted from the Norwegian Knee
      Ligament Registry at 3 postoperative time points: 397 at 6 months, 400 at 12
      months, and 400 at 24 months. The inclusion criterion was unilateral primary
      ACLR. Questions about acceptable symptoms and treatment failure and the KOOS
      questionnaire were sent to the patients, and those who answered "yes" to the
      acceptable symptoms question were considered to have acceptable symptoms.
      Patients who answered "no" to the same question and "yes" to the treatment
      failure question were considered to have treatment failure. Mean KOOS values and
      95% CIs were calculated for each category. RESULTS: A complete data set was
      obtained from 598 (50%) responders. Fifty-five percent of the patients perceived
      their symptoms as acceptable at 6-month follow-up versus 66% at 12- to 24-month
      follow-up. Similarly, 7% at 6-month follow-up perceived their treatment to have
      failed versus 12% at 12- to 24-month follow-up. Postoperative mean KOOS subscale
      values ranged from 72 (95% CI, 70-74) to 95 (95% CI, 94-96) for patients with
      acceptable symptoms and from 28 (95% CI, 22-34) to 71 (95% CI, 65-76) for
      patients with treatment failure. For both categories, the worst subscale values
      were seen in the sport and recreation and quality of life subscales and the best
      in the activities of daily living subscale. CONCLUSION: Only half of the patients
      at 6 months and about two-thirds at 1 to 2 years perceived their symptoms as
      acceptable after ACLR. For these patients, KOOS values reflected no problems to
      mild problems on average, while for patients reporting treatment failure, KOOS
      values reflected moderate to severe problems.

PMID- 25977524
TI  - Registry data highlight increased revision rates for endobutton/biosure HA in ACL
      reconstruction with hamstring tendon autograft: a nationwide cohort study from
      the Norwegian Knee Ligament Registry, 2004-2013.
AB  - BACKGROUND: Compared with a patellar tendon autograft (PT), a hamstring tendon
      autograft (HT) has an increased risk of revision after anterior cruciate ligament
      reconstruction (ACLR). There are no studies analyzing whether this can be
      explained by inferior fixation devices used in HT reconstruction or whether the
      revision risk of ACLR with an HT or a PT is influenced by the graft fixation.
      PURPOSE: To compare the risk of revision and the revision rates between the most
      commonly used combinations of fixation for HTs with PTs. STUDY DESIGN: Cohort
      study; Level of evidence, 2. METHODS: This study included all patients registered
      in the Norwegian Knee Ligament Registry from 2004 through 2013 who underwent
      primary PT or HT ACLR with no concomitant ligament injury and known graft
      fixation. The 2-year revision rates were calculated using the Kaplan-Meier
      analysis. Hazard ratios (HRs) for revision at 2 years were calculated using
      multivariate Cox regression models. RESULTS: A total of 14,034 patients with
      primary ACLR were identified: 3806 patients with PTs and 10,228 patients with
      HTs; the mean follow-up time was 4.5 years. In the HT group, 5 different
      combinations of fixation in the femur/tibia were used in more than 500 patients:
      Endobutton/RCI screw (n = 2339), EZLoc/WasherLoc (n = 1352), Endobutton/Biosure
      HA (n = 1209), Endobutton/Intrafix (n = 687), and TransFix II/metal interference
      screw (MIS) (n = 620). The crude 2-year revision rate for patients with PTs was
      0.7% (95% CI, 0.4%-1.0%), and for patients with HTs, it ranged between the groups
      from 1.5% (95% CI, 0.5%-2.4%) for TransFix II/MIS to 5.5% (95% CI, 4.0%-7.0%) for
      Endobutton/Biosure HA. When adjusted for detected confounding factors and
      compared with patients with PTs, the HR for revision at 2 years was increased for
      all HT combinations used in more than 500 patients, and the combinations
      Endobutton/Biosure HA and Endobutton/Intrafix had the highest HRs of 7.3 (95% CI,
      4.4-12.1) and 5.5 (95% CI, 3.1-9.9), respectively. CONCLUSION: The choice of
      fixation after ACLR with an HT has a significant effect on a patient's risk of
      revision. In this study population, none of the examined combinations of HT
      fixation had a revision rate as low as that for a PT.

PMID- 25977525
TI  - Science in U.S.-Cuba relations.

PMID- 25977527
TI  - Biomedicine. Newborn screening collides with privacy fears.

PMID- 25977528
TI  - Avian influenza. Enigmatic bird flu strain races across the U.S. Midwest.

PMID- 25977529
TI  - Infectious diseases. Ebola survivors fight back in plasma studies.

PMID- 25977530
TI  - Evolution. How birds got their beaks.

PMID- 25977531
TI  - Infectious diseases. Rules of the name.

PMID- 25977532
TI  - In from the cold.

PMID- 25977533
TI  - Fidel Castro's first-born son foments a nanotech revolution.

PMID- 25977534
TI  - Graying Cuba strains socialist safety net.

PMID- 25977535
TI  - Cuba's coral Eden.

PMID- 25977536
TI  - RNA. Phased piRNAs tackle transposons.

PMID- 25977537
TI  - Geophysics. Probing the underbelly of a supervolcano.

PMID- 25977538
TI  - Ocean chemistry. The missing link in oceanic phosphorus cycling?

PMID- 25977539
TI  - Cancer immunotherapy. Neo approaches to cancer vaccines.

PMID- 25977540
TI  - Public health. Linking funds to actions for global health emergencies.

PMID- 25977541
TI  - Rethinking migration.

PMID- 25977542
TI  - The Nobel pulsar.

PMID- 25977543
TI  - Preparing for disasters.

PMID- 25977544
TI  - Social psychology. Comment on "Morality in everyday life".
AB  - In examining morality in everyday life, Hofmann et al. (Reports, 12 September
      2014, p. 1340) conclude that being the target of (im)moral deeds impacts
      happiness, whereas committing them primarily affects one's sense of purpose. I
      point to shortcomings in the analyses and interpretations and caution that, based
      on the methodological approach, conclusions about everyday life relationships
      between morality and happiness/purpose are premature. 

PMID- 25977545
TI  - Social psychology. Response to Comment on "Morality in everyday life".
AB  - Voelkle challenges our conclusions regarding the relationship between morality
      and momentary happiness/sense of purpose based on methodological concerns. We
      show that our main conclusions are not affected by this methodological critique
      and clarify that the discrepancies between our and Voelkle's effect size
      estimates can be reconciled by the realization that two different (but
      compatible) research questions are being asked. 

PMID- 25977546
TI  - Quantum optics. Quantum dynamics of an electromagnetic mode that cannot contain N
      photons.
AB  - Electromagnetic modes are instrumental in building quantum machines. In this
      experiment, we introduce a method to manipulate these modes by effectively
      controlling their phase space. Preventing access to a single energy level,
      corresponding to a number of photons N, confined the dynamics of the field to
      levels 0 to N - 1. Under a resonant drive, the level occupation was found to
      oscillate in time, similarly to an N-level system. Performing a direct Wigner
      tomography of the field revealed its nonclassical features, including a
      Schrodinger cat-like state at half period in the evolution. This fine control of
      the field in its phase space may enable applications in quantum information and
      metrology. 

PMID- 25977547
TI  - Galaxy evolution. Quasar quartet embedded in giant nebula reveals rare massive
      structure in distant universe.
AB  - All galaxies once passed through a hyperluminous quasar phase powered by
      accretion onto a supermassive black hole. But because these episodes are brief,
      quasars are rare objects typically separated by cosmological distances. In a
      survey for Lyman-alpha emission at redshift z ~ 2, we discovered a physical
      association of four quasars embedded in a giant nebula. Located within a
      substantial overdensity of galaxies, this system is probably the progenitor of a
      massive galaxy cluster. The chance probability of finding a quadruple quasar is
      estimated to be ~10(-7), implying a physical connection between Lyman-alpha
      nebulae and the locations of rare protoclusters. Our findings imply that the most
      massive structures in the distant universe have a tremendous supply (?10(11)
      solar masses) of cool dense (volume density ? 1 cm(-3)) gas, which is in conflict
      with current cosmological simulations. 

PMID- 25977548
TI  - Phosphorus cycling. Major role of planktonic phosphate reduction in the marine
      phosphorus redox cycle.
AB  - Phosphorus in the +5 oxidation state (i.e., phosphate) is the most abundant form
      of phosphorus in the global ocean. An enigmatic pool of dissolved phosphonate
      molecules, with phosphorus in the +3 oxidation state, is also ubiquitous;
      however, cycling of phosphorus between oxidation states has remained poorly
      constrained. Using simple incubation and chromatography approaches, we measured
      the rate of the chemical reduction of phosphate to P(III) compounds in the
      western tropical North Atlantic Ocean. Colonial nitrogen-fixing cyanobacteria in
      surface waters played a critical role in phosphate reduction, but other classes
      of plankton, including potentially deep-water archaea, were also involved. These
      data are consistent with marine geochemical evidence and microbial genomic
      information, which together suggest the existence of a vast oceanic phosphorus
      redox cycle. 

PMID- 25977549
TI  - Animal physiology. Whole-body endothermy in a mesopelagic fish, the opah, Lampris
      guttatus.
AB  - Endothermy (the metabolic production and retention of heat to warm body
      temperature above ambient) enhances physiological function, and whole-body
      endothermy generally sets mammals and birds apart from other animals. Here, we
      describe a whole-body form of endothermy in a fish, the opah (Lampris guttatus),
      that produces heat through the constant "flapping" of wing-like pectoral fins and
      minimizes heat loss through a series of counter-current heat exchangers within
      its gills. Unlike other fish, opah distribute warmed blood throughout the body,
      including to the heart, enhancing physiological performance and buffering
      internal organ function while foraging in the cold, nutrient-rich waters below
      the ocean thermocline. 

PMID- 25977550
TI  - Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact
      and injured zebrafish brain.
AB  - Adult neural stem cells are the source for restoring injured brain tissue. We
      used repetitive imaging to follow single stem cells in the intact and injured
      adult zebrafish telencephalon in vivo and found that neurons are generated by
      both direct conversions of stem cells into postmitotic neurons and via
      intermediate progenitors amplifying the neuronal output. We observed an imbalance
      of direct conversion consuming the stem cells and asymmetric and symmetric self
      renewing divisions, leading to depletion of stem cells over time. After brain
      injury, neuronal progenitors are recruited to the injury site. These progenitors
      are generated by symmetric divisions that deplete the pool of stem cells, a mode
      of neurogenesis absent in the intact telencephalon. Our analysis revealed changes
      in the behavior of stem cells underlying generation of additional neurons during
      regeneration. 

PMID- 25977551
TI  - Human behavior. Sex equality can explain the unique social structure of hunter
      gatherer bands.
AB  - The social organization of mobile hunter-gatherers has several derived features,
      including low within-camp relatedness and fluid meta-groups. Although these
      features have been proposed to have provided the selective context for the
      evolution of human hypercooperation and cumulative culture, how such a
      distinctive social system may have emerged remains unclear. We present an agent
      based model suggesting that, even if all individuals in a community seek to live
      with as many kin as possible, within-camp relatedness is reduced if men and women
      have equal influence in selecting camp members. Our model closely approximates
      observed patterns of co-residence among Agta and Mbendjele BaYaka hunter
      gatherers. Our results suggest that pair-bonding and increased sex egalitarianism
      in human evolutionary history may have had a transformative effect on human
      social organization. 

PMID- 25977553
TI  - Noncoding RNA. piRNA-guided slicing specifies transcripts for Zucchini-dependent,
      phased piRNA biogenesis.
AB  - In animal gonads, PIWI-clade Argonaute proteins repress transposons sequence
      specifically via bound Piwi-interacting RNAs (piRNAs). These are processed from
      single-stranded precursor RNAs by largely unknown mechanisms. Here we show that
      primary piRNA biogenesis is a 3'-directed and phased process that, in the
      Drosophila germ line, is initiated by secondary piRNA-guided transcript cleavage.
      Phasing results from consecutive endonucleolytic cleavages catalyzed by Zucchini,
      implying coupled formation of 3' and 5' ends of flanking piRNAs. Unexpectedly,
      Zucchini also participates in 3' end formation of secondary piRNAs. Its function
      can, however, be bypassed by downstream piRNA-guided precursor cleavages coupled
      to exonucleolytic trimming. Our data uncover an evolutionarily conserved piRNA
      biogenesis mechanism in which Zucchini plays a central role in defining piRNA 5'
      and 3' ends. 

PMID- 25977552
TI  - Centrosomes. Regulated assembly of a supramolecular centrosome scaffold in vitro.
AB  - The centrosome organizes microtubule arrays within animal cells and comprises two
      centrioles surrounded by an amorphous protein mass called the pericentriolar
      material (PCM). Despite the importance of centrosomes as microtubule-organizing
      centers, the mechanism and regulation of PCM assembly are not well understood. In
      Caenorhabditis elegans, PCM assembly requires the coiled-coil protein SPD-5. We
      found that recombinant SPD-5 could polymerize to form micrometer-sized porous
      networks in vitro. Network assembly was accelerated by two conserved regulators
      that control PCM assembly in vivo, Polo-like kinase-1 and SPD-2/Cep192. Only the
      assembled SPD-5 networks, and not unassembled SPD-5 protein, functioned as a
      scaffold for other PCM proteins. Thus, PCM size and binding capacity emerge from
      the regulated polymerization of one coiled-coil protein to form a porous network.

PMID- 25977555
TI  - Accounting for career breaks.

PMID- 25977554
TI  - Noncoding RNA. piRNA-guided transposon cleavage initiates Zucchini-dependent,
      phased piRNA production.
AB  - PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing
      transposons. Primary piRNAs, generated from transcripts of genomic transposon
      "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding
      secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein
      Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The
      first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the
      subsequent ~26 nt become the first in a series of phased primary piRNAs that bind
      Piwi, allowing piRNAs to spread beyond the site of RNA cleavage. The ping-pong
      pathway increases only the abundance of piRNAs, whereas production of phased
      primary piRNAs from cleaved transposon RNAs adds sequence diversity to the piRNA
      pool, allowing adaptation to changes in transposon sequence. 

PMID- 25977556
TI  - Erratum for the report "Morality in everyday life" by W. Hofmann, D. C. Wisneski,
      M. J. Brandt, L. J. Skitka.

PMID- 25977558
TI  - Development economics. A multifaceted program causes lasting progress for the
      very poor: evidence from six countries.
AB  - We present results from six randomized control trials of an integrated approach
      to improve livelihoods among the very poor. The approach combines the transfer of
      a productive asset with consumption support, training, and coaching plus savings
      encouragement and health education and/or services. Results from the
      implementation of the same basic program, adapted to a wide variety of geographic
      and institutional contexts and with multiple implementing partners, show
      statistically significant cost-effective impacts on consumption (fueled mostly by
      increases in self-employment income) and psychosocial status of the targeted
      households. The impact on the poor households lasted at least a year after all
      implementation ended. It is possible to make sustainable improvements in the
      economic status of the poor with a relatively short-term intervention. 

PMID- 25977557
TI  - Cell biology. On being the right (cell) size.
AB  - Different animal cell types have distinctive and characteristic sizes. How a
      particular cell size is specified by differentiation programs and physiology
      remains one of the fundamental unknowns in cell biology. In this Review, we
      explore the evidence that individual cells autonomously sense and specify their
      own size. We discuss possible mechanisms by which size-sensing and size
      specification may take place. Last, we explore the physiological implications of
      size control: Why is it important that particular cell types maintain a
      particular size? We develop these questions through examination of the current
      literature and pose the questions that we anticipate will guide this field in the
      upcoming years. 

PMID- 25977559
TI  - Application of the Extreme Value Distribution to Estimate the Uncertainty of Peak
      Sound Pressure Levels at the Workplace.
AB  - OBJECTIVES: The purpose of this article is to develop a method for the
      statistical inference of the maximum peak sound pressure level and of the
      associated uncertainty. Both quantities are requested by the EU directive
      2003/10/EC for a complete and solid assessment of the noise exposure at the
      workplace. METHODS: Based on the characteristics of the sound pressure waveform,
      it is hypothesized that the distribution of the measured peak sound pressure
      levels follows the extreme value distribution. The maximum peak level is
      estimated as the largest member of a finite population following this probability
      distribution. The associated uncertainty is also discussed, taking into account
      not only the contribution due to the incomplete sampling but also the
      contribution due to the finite precision of the instrumentation. RESULTS: The
      largest of the set of measured peak levels underestimates the maximum peak sound
      pressure level. The underestimate can be as large as 4 dB if the number of
      measurements is limited to 3-4, which is common practice in occupational noise
      assessment. The extended uncertainty is also quite large (~2.5 dB), with a weak
      dependence on the sampling details. CONCLUSIONS: Following the procedure outlined
      in this article, a reliable comparison between the peak sound pressure levels
      measured in a workplace and the EU directive action limits is possible. Non
      compliance can occur even when the largest of the set of measured peak levels is
      several dB below such limits.

PMID- 25977561
TI  - Persistence of subclinical sonographic joint activity in rheumatoid arthritis in
      sustained clinical remission.
AB  - BACKGROUND: Sonographic assessment, measuring grey scale (GS) and power Doppler
      (PD) signals, is a sensitive tool for the evaluation of inflammatory joint
      activity in patients with rheumatoid arthritis (RA). We evaluated the persistence
      of PD and GS signals in previously clinically active RA joints that have reached
      a state of continuous clinical inactivity. METHODS: We performed sonographic
      imaging of 22 joints of the hands of patients with RA, selected all joints
      without clinical activity but showing ongoing sonographic signs of inflammation,
      and evaluated the time from last clinical joint activity. RESULTS: A total of 90
      patients with RA with 1980 assessed joints were included in this study. When
      comparing the mean time from clinical swelling, we found a significantly longer
      period of clinical inactivity in joints showing low sonographic activity (mean+/
      SD time from swelling of 4.1+/-3.2 vs 3.1+/-2.9 years for PD1 vs PD>=2, p=0.031
      and 4.5+/-3.4 vs 3.3+/-3.2 years for GS1 vs GS>=2, p<=0.0001). CONCLUSIONS: We
      conclude that subclinical joint activity is long-lasting in RA joints in clinical
      remission, but attenuates over time. The latter conclusion is based on the
      observed shorter time duration from last clinical activity for strong compared
      with weaker sonographic signals.

PMID- 25977560
TI  - Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer
      Case-Control Consortium.
AB  - BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer
      is unclear, with recent studies suggesting both positive and negative
      associations. PATIENTS AND METHODS: We used data from nine case-control studies
      from the International Pancreatic Cancer Case-Control Consortium (PanC4) to
      examine associations between pancreatic cancer risk and dietary vitamin D intake.
      Study-specific odds ratios (ORs) were estimated using multivariable logistic
      regression, and ORs were then pooled using a random-effects model. From a subset
      of four studies, we also calculated pooled estimates of association for
      supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer
      increased with dietary intake of vitamin D [per 100 international units (IU)/day:
      OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 * 10(-6), P
      heterogeneity = 0.52; >=230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P =
      2.4 * 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in
      people with low retinol/vitamin A intake. CONCLUSION: Increased risk of
      pancreatic cancer was observed with higher levels of dietary vitamin D intake.
      Additional studies are required to determine whether or not our finding has a
      causal basis.

PMID- 25977562
TI  - From Modic 1 vertebral-endplate subchondral bone signal changes detected by MRI
      to the concept of 'active discopathy'.
AB  - Late-1980s MRI-detected vertebral-endplate subchondral bone signal changes
      associated with degenerative disc disease as well as recent studies suggest that
      in some patients, non-specific chronic low back pain (NS cLBP) can be defined by
      specific clinical, radiological and biological features, for a concept of active
      discopathy. This concept allows for associating a particular NS cLBP phenotype to
      a specific anatomical lesion, namely those with Modic 1 signal changes seen on
      MRI. Local inflammation is thought to play a pivotal role in these changes. Other
      etiopathogenic processes may include local infection and mechanical or
      biochemical stress combined with predisposing genetic factors; treatment
      strategies remain debated. Modic 1 changes detected by MRI can be considered a
      first biomarker in NS cLBP. Such changes are of high clinical relevance because
      they are associated with a specific clinical phenotype and can be targeted by
      specific treatments. 

PMID- 25977563
TI  - Drug use in French children: a population-based study.
AB  - BACKGROUND AND OBJECTIVE: To provide an overview of drug use in outpatient
      children in France, a population-based study using a national reimbursement
      claims database representative of 90% of the French population was conducted.
      DESIGN: Cross-sectional study performed between January and December 2011 using
      the EGB database (Echantillon Generaliste de Beneficiaires), a 1/97th sample of
      the national healthcare insurance system beneficiaries. Drug use in children <18
      years old was estimated through reimbursements for prescribed drugs excluding
      vaccines. Prevalences of use were calculated for different levels of the
      Anatomical Therapeutic Chemical classification by considering as users children
      who had at least one reimbursement during the study period. RESULTS: In 2011,
      133,800 children were included in the study. The overall prevalence of drug use
      was 84% and the median number of different drugs per child was 5. Drug use was
      greatest in children aged <2 years. The most widely used drugs were paracetamol,
      systemic anti-infectives, nasal corticosteroids and decongestants, and anti
      histamines. 21% children <2 years received domperidone. CONCLUSIONS: There is
      widespread use of medicines that are unlikely to be effective and may have
      significant toxicity in French children. Irrational use of medicines appears to
      be greatest in children aged 5 years and under.

PMID- 25977564
TI  - Who's afraid of fever?

PMID- 25977566
TI  - Circulating Markers of Liver Function and Cardiovascular Disease Risk.
AB  - Measurement of serum concentrations of various liver enzymes and other
      nonenzymatic proteins and metabolites of heme metabolism (eg, bilirubin) is often
      undertaken in clinical practice. Measurement of these liver function tests is
      simple, quick, and relatively inexpensive. However, interpreting the liver
      function test results in patients without evidence of liver disease is often
      challenging. Concentrations of some of liver enzymes, such as gamma
      glutamyltransferase or alkaline phosphatase, and concentrations of liver-derived
      metabolites, such as bilirubin, may be influenced by metabolic processes beyond
      the liver, sometimes making interpretation of the test results difficult. This
      scenario frequently occurs both in individuals at risk of cardiovascular disease
      and in patients with known cardiovascular disease, often resulting in the
      clinicians ignoring the test results. In this brief review, we discuss the
      evidence for associations between key serum liver function tests and
      cardiovascular disease risk and where associations are robust; we provide an
      interpretation for possible mechanistic links between the liver function test and
      cardiovascular disease. 

PMID- 25977565
TI  - Reduction of Mitochondria-Endoplasmic Reticulum Interactions by Acetylcholine
      Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation
      Injury.
AB  - OBJECTIVE: We explored the role of endoplasmic reticulum (ER)-mitochondria Ca(2+)
      cross talk involving voltage-dependent anion channel-1 (VDAC1)/glucose-regulated
      protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 in
      endothelial cells during hypoxia/reoxygenation (H/R), and investigated the
      protective effects of acetylcholine. APPROACH AND RESULTS: Acetylcholine
      treatment during reoxygenation prevented intracellular and mitochondrial Ca(2+)
      increases and alleviated ER Ca(2+) depletion during H/R in human umbilical vein
      endothelial cells. Consequently, acetylcholine enhanced mitochondrial membrane
      potential and inhibited proapoptotic cascades, thereby reducing cell death and
      preserving endothelial ultrastructure. This effect was likely mediated by the
      type-3 muscarinic acetylcholine receptor and the phosphatidylinositol 3
      kinase/Akt pathway. In addition, interactions among members of the VDAC1/glucose
      regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex were
      increased after H/R and were associated with mitochondrial Ca(2+) overload and
      cell death. Inhibition of the partner of the Ca(2+) channeling complex (VDAC1
      siRNA) or a reduction in ER-mitochondria tethering (mitofusin 2 siRNA) prevented
      the increased protein interaction within the complex and reduced mitochondrial
      Ca(2+) accumulation and subsequent endothelial cell death after H/R.
      Intriguingly, acetylcholine could modulate ER-mitochondria Ca(2+) cross talk by
      inhibiting the VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate
      receptor 1 complex and mitofusin 2 expression. Phosphatidylinositol 3-kinase
      siRNA diminished acetylcholine-mediated inhibition of mitochondrial Ca(2+)
      overload and VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate
      receptor 1 complex formation induced by H/R. CONCLUSIONS: Our data suggest that
      ER-mitochondria interplay plays an important role in reperfusion injury in the
      endothelium and may be a novel molecular target for endothelial protection.
      Acetylcholine attenuates both intracellular and mitochondrial Ca(2+) overload and
      protects endothelial cells from H/R injury, presumably by disrupting the ER
      mitochondria interaction.

PMID- 25977567
TI  - 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid
      Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy.
AB  - OBJECTIVE: A feature of vulnerable atherosclerotic plaques of the carotid artery
      is high activity and abundance of lesion macrophages. There is consensus that
      this is of importance for plaque vulnerability, which may lead to clinical
      events, such as stroke and transient ischemic attack. We used positron emission
      tomography (PET) and the novel PET ligand [(64)Cu] [1,4,7,10
      tetraazacyclododecane-N,N',N",N'''-tetraacetic acid]-d-Phe1,Tyr3-octreotate
      ((64)Cu-DOTATATE) to specifically target macrophages via the somatostatin
      receptor subtype-2 in vivo. APPROACH AND RESULTS: Ten patients underwent
      simultaneous PET/MRI to measure (64)Cu-DOTATATE uptake in carotid artery plaques
      before carotid endarterectomy. (64)Cu-DOTATATE uptake was significantly higher in
      symptomatic plaque versus the contralateral carotid artery (P<0.001).
      Subsequently, a total of 62 plaque segments were assessed for gene expression of
      selected markers of plaque vulnerability using real-time quantitative polymerase
      chain reaction. These results were compared with in vivo (64)Cu-DOTATATE uptake
      calculated as the mean standardized uptake value. Univariate analysis of real
      time quantitative polymerase chain reaction and PET showed that cluster of
      differentiation 163 (CD163) and CD68 gene expression correlated significantly but
      weakly with mean standardized uptake value in scans performed 85 minutes post
      injection (P<0.001 and P=0.015, respectively). Subsequent multivariate analysis
      showed that CD163 correlated independently with (64)Cu-DOTATATE uptake (P=0.031)
      whereas CD68 did not contribute significantly to the final model. CONCLUSIONS:
      The novel PET tracer (64)Cu-DOTATATE accumulates in atherosclerotic plaques of
      the carotid artery. CD163 gene expression correlated independently with (64)Cu
      DOTATATE uptake measured by real-time quantitative polymerase chain reaction in
      the final multivariate model, indicating that (64)Cu-DOTATATE PET is detecting
      alternatively activated macrophages. This association could potentially improve
      noninvasive identification and characterization of vulnerable plaques.

PMID- 25977568
TI  - Resident Endothelial Cells and Endothelial Progenitor Cells Restore Endothelial
      Barrier Function After Inflammatory Lung Injury.
AB  - OBJECTIVE: Disruption of endothelial barrier integrity is a characteristic of
      many inflammatory conditions. However, the origin and function of endothelial
      cells (ECs) restoring endothelial barrier function remain unknown. This study
      defined the roles of resident ECs (RECs) and bone marrow-derived endothelial
      progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic
      lung injury. APPROACH AND RESULTS: We generated mice that enable to quantify
      proliferating RECs or BMDEPCs and also to study the causal link between REC or
      BMDEPC proliferation and endothelial barrier restoration. Using these mouse
      models, we showed that endothelial barrier restoration was associated with
      increased REC and BMDEPC proliferation. RECs and BMDEPCs participate in barrier
      repair. Immunofluorescence staining demonstrated that RECs proliferate in situ on
      endothelial layer and that BMDEPCs are engrafted into endothelial layer of lung
      microvessels at the active barrier repair phase. In lungs, 8 weeks after
      lipopolysaccharide-induced injury, the number of REC-derived ECs (CD45(
      )/CD31(+)/BrdU(+)/rtTA(+)) or BMDEPC-derived ECs (CD45(-)/CD31(+)/eNOS(+)/GFP(+))
      increased by 22- or 121-fold, respectively. The suppression of REC or BMDEPC
      proliferation by blocking REC or BMDEPC intrinsic nuclear factor-kappaB at the
      barrier repair phase was associated with an augmented endothelial permeability
      and impeded endothelial barrier recovery. RECs and BMDEPCs contributed
      differently to endothelial barrier repair. In lungs, 8 weeks after
      lipopolysaccharide-induced injury, REC-derived ECs constituted 22%, but BMDEPC
      derived ECs constituted only 3.7% of the total new ECs. CONCLUSIONS: REC is a
      major and BMDEPC is a complementary source of new ECs in endothelial barrier
      restoration. RECs and BMDEPCs play important roles in endothelial barrier
      restoration after inflammatory lung injury.

PMID- 25977569
TI  - Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F2alpha
      Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese
      Population.
AB  - OBJECTIVE: To investigate whether rs12731181 (A->G) interrupted miR-590-3p
      mediated suppression of the prostaglandin F2alpha receptor (FP) and whether it is
      associated with essential hypertension in the Chinese population. APPROACH AND
      RESULTS: We found that miR-590-3p regulates human FP gene expression by binding
      to its 3'-untranslated region. rs12731181 (A->G) altered the binding affinity
      between miR-590-3p and its FP 3'-untranslated region target, thus reducing the
      suppression of FP expression, which, in turn, enhanced FP receptor-mediated
      contractility of vascular smooth muscle cells. Overexpression of FP augmented
      vascular tone and elevated blood pressure in mice. An association study was
      performed to analyze the relationship between the FP gene and essential
      hypertension in the Han Chinese population. The results indicated that the
      rs12731181 G allele was associated with susceptibility to essential hypertension.
      Carriers of the AG genotype exhibited significantly higher blood pressure than
      those of the AA genotype. FP gene expression was significantly higher in human
      peripheral leukocytes from individuals with the AG genotype than that in
      leukocytes from individuals with the AA genotype. CONCLUSIONS: rs12731181 in the
      seed region of the miR-590-3p target site is associated with increased risk of
      essential hypertension and represents a new paradigm for FP involvement in blood
      pressure regulation.

PMID- 25977571
TI  - Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis.
AB  - OBJECTIVES: Salubrinal is a synthetic agent that elevates phosphorylation of
      eukaryotic translation initiation factor 2 alpha (eIF2alpha) and alleviates
      stress to the endoplasmic reticulum. Previously, we reported that in
      chondrocytes, Salubrinal attenuates expression and activity of matrix
      metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B
      (NFkappaB) signalling. We herein examine whether Salubrinal prevents the
      degradation of articular cartilage in a mouse model of osteoarthritis (OA).
      METHODS: OA was surgically induced in the left knee of female mice. Animal groups
      included age-matched sham control, OA placebo, and OA treated with Salubrinal or
      Guanabenz. Three weeks after the induction of OA, immunoblotting was performed
      for NFkappaB p65 and p-NFkappaB p65. At three and six weeks, the femora and
      tibiae were isolated and the sagittal sections were stained with Safranin O.
      RESULTS: Salubrinal suppressed the progression of OA by downregulating p-NFkappaB
      p65 and MMP13. Although Guanabenz elevates the phosphorylation level of
      eIF2alpha, it did not suppress the progression of OA. CONCLUSIONS: Administration
      of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can
      be considered as a potential therapeutic agent for alleviating symptoms of OA.
      Cite this article: Bone Joint Res 2015;4:84-92.

PMID- 25977572
TI  - Increases in physical activity is as important as smoking cessation for reduction
      in total mortality in elderly men: 12 years of follow-up of the Oslo II study.
AB  - BACKGROUND: Physical activity (PA) at leisure by the elderly, and its
      relationship to cardiovascular (CV) and non-CV mortality, with and without
      competing risk, has been scarcely described. We determined the relationships
      between PA, smoking and 12-year CV, non-CV and all-cause mortality in elderly
      Oslo men screened for CV disease in 1972-1973 and 2000. METHODS: Among 14,846 men
      born during 1923-1932 and participating in 1972-1973, there were 5738
      participants in 2000. During the 12 years follow-up 2154 died. Cox regression
      modelling of mortality endpoints, with and without competing risk, was applied
      analysing PA variables hours per week of light or vigorous PA intensity and
      degree of PA at leisure. Comparisons of predictive ability between PA and smoking
      were done by receiver operating characteristics. RESULTS: Thirty minutes of PA
      per 6 days a week was associated with about 40% mortality risk reduction. There
      was a 5 years increased lifetime when comparing sedentary and moderate to
      vigorous physically active men. Associations to CV or non-CV mortality were
      slightly weakened, allowing competing risk. Conditional on the prevalence of
      smoking and PA, the degree of PA at leisure was almost as predictive as smoking
      with regard to the effects on mortality. Increase in PA was as beneficial as
      smoking cessation in reducing mortality. CONCLUSIONS: Even at the age of 73
      years, PA is associated highly with mortality between groups of sedentary and
      active persons. Allowing for competing risk did not weaken these associations
      markedly. Public health strategies in elderly men should include efforts to
      increase PA in line with efforts to reduce smoking behaviour.

PMID- 25977570
TI  - Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel
      Associations Between Key Biological Processes and Coronary Artery Disease.
AB  - OBJECTIVE: Genome-wide association studies have identified multiple genetic
      variants affecting the risk of coronary artery disease (CAD). However,
      individually these explain only a small fraction of the heritability of CAD and
      for most, the causal biological mechanisms remain unclear. We sought to obtain
      further insights into potential causal processes of CAD by integrating large
      scale GWA data with expertly curated databases of core human pathways and
      functional networks. APPROACHES AND RESULTS: Using pathways (gene sets) from
      Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a
      meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets
      (9889 cases/11 089 controls), nominally significant gene sets were tested for
      replication in a meta-analysis of 9 additional studies (15 502 cases/55 730
      controls) from the Coronary ARtery DIsease Genome wide Replication and Meta
      analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested
      showed convincing association with CAD (replication P<0.05). These pathways
      resided in 9 of 21 core biological processes represented in Reactome, and
      included pathways relevant to extracellular matrix (ECM) integrity, innate
      immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor),
      NOTCH, and the transforming growth factor-beta/SMAD receptor complex. Many of
      these pathways had strengths of association comparable to those observed in lipid
      transport pathways. Network analysis of unique genes within the replicated
      pathways further revealed several interconnected functional and topologically
      interacting modules representing novel associations (eg, semaphoring-regulated
      axonal guidance pathway) besides confirming known processes (lipid metabolism).
      The connectivity in the observed networks was statistically significant compared
      with random networks (P<0.001). Network centrality analysis (degree and
      betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play
      critical roles in the maintenance and functioning of several of the replicated
      pathways. CONCLUSIONS: These findings provide novel insights into how genetic
      variation, interpreted in the context of biological processes and functional
      interactions among genes, may help define the genetic architecture of CAD.

PMID- 25977573
TI  - Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis.
AB  - BACKGROUND: Microbiological culture of cerebrospinal fluid is the gold standard
      to differentiate between aseptic and bacterial meningitis, but this method has
      low sensitivity. A fast and reliable new marker would be of interest in clinical
      practice. OBJECTIVE: Interleukin-6, secreted by T cells in response to meningeal
      pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a
      marker of acute meningitis. DESIGN AND METHODS: A total of 150 cerebrospinal
      fluid samples were analysed by an electrochemiluminescence method, selected
      according to patient diagnosis: (a) bacterial meningitis confirmed by positive
      culture (n = 26); (b) bacterial meningitis with negative culture or not performed
      (n = 15); (c) viral meningitis confirmed by polymerase chain reaction or
      immunoglobulin G determination (n = 23); (d) viral meningitis with polymerase
      chain reaction negative or not performed (n = 42); and (e) controls (n = 44).
      RESULTS: Cerebrospinal fluid interleukin-6 concentration showed significant
      differences between all pathologic groups and the control group (P < 0.001). As a
      diagnostic tool for bacterial meningitis, interleukin-6 showed an area under the
      curve of 0.937 (95% confidence intervals: 0.895-0.978), significantly higher than
      those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5%
      sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6%
      sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis.
      CONCLUSION: Interleukin-6 measured by electrochemiluminescence method is a
      promising marker for early differentiation between aseptic and bacterial
      meningitis. More studies are needed to validate clinical implications for future
      practice in an emergency laboratory.

PMID- 25977574
TI  - Age-adjusted glycated albumin accurately reflects blood glucose in patients with
      neonatal diabetes mellitus: comparison with calculated glycated albumin
      determined by past blood glucose concentrations.
AB  - BACKGROUND: Glycated albumin is a useful glycaemic control indicator for neonatal
      diabetes mellitus. However, glycated albumin concentrations in infants are lower
      than those in adults and increase in an age-dependent manner. Based on our
      investigation of non-diabetic subjects, we proposed the possibility that the
      reference range for adults may be used regardless of age, provided that age
      adjusted glycated albumin is employed. In the present study, we evaluate the
      usefulness of age-adjusted glycated albumin in neonatal diabetes mellitus
      patients. METHODS: Six neonatal diabetes mellitus patients (four patients with
      permanent neonatal diabetes mellitus and two patients with transient neonatal
      diabetes mellitus) were included. Measured glycated albumin or age-adjusted
      glycated albumin was compared to calculated glycated albumin, which was
      determined using calculation formulae we had reported based on past blood glucose
      over the 50 days before measurement of glycated albumin. RESULTS: Measured
      glycated albumin was significantly lower than calculated glycated albumin (20.5
      +/- 4.9% versus 28.2 +/- 6.1%; p < 0.0001), whereas age-adjusted glycated albumin
      was equivalent to calculated glycated albumin, showing no significant difference
      (27.5 +/- 6.8% versus 28.2 +/- 6.1%). Measured glycated albumin concentrations in
      patients with transient neonatal diabetes mellitus in remission were lower than
      the reference range for adults, whereas age-adjusted glycated albumin
      concentrations were within the reference range for adults. CONCLUSION: We
      demonstrated that age-adjusted glycated albumin concentrations were consistent
      with calculated glycated albumin. Age-adjusted glycated albumin is therefore a
      useful glycaemic control indicator for neonatal diabetes mellitus patients.

PMID- 25977575
TI  - ISO standards for pathology - a step too far?
AB  - The International Standard, ISO 15189 which specifies requirements for quality
      and competence in medical laboratories was written by medical laboratory
      professionals. Since its first publication in 2003, it has raised awareness of
      the importance of medical laboratories with governments throughout the world and
      provided a tool with which laboratories may develop their quality management
      systems and assess their own competence. This paper examines the use of the
      Standard in the context of self-assessment, accreditation and regulation of
      medical laboratories. 

PMID- 25977576
TI  - Visual rating method and tensor-based morphometry in the diagnosis of mild
      cognitive impairment and Alzheimer's disease: a comparative magnetic resonance
      imaging study.
AB  - BACKGROUND: Atrophy of the medial temporal lobe (MTL) is the main structural
      magnetic resonance imaging (MRI) finding in the brain of patients with
      Alzheimer's disease (AD). However, evaluating the degree of atrophy is still
      demanding. PURPOSE: The visual rating method (VRM) was compared with multi
      template tensor-based morphometry (TBM), in terms of its efficacy in diagnosing
      of mild cognitive impairment (MCI) and AD. MATERIAL AND METHODS: Forty-seven
      patients with MCI, 80 patients with AD and 84 controls were studied. RESULTS: TBM
      seems to be more sensitive than VRM at the early stage of dementia in the areas
      of MTL and ventricles. The methods were equally good in distinguishing controls
      and the MCI group from the AD group. At the frontal areas TBM was better than VRM
      in all comparisons. CONCLUSION: A user-friendly VRM is still useful for the
      clinical evaluation of MCI patients, but multi-template TBM is more sensitive for
      diagnosing the early stages of dementia. However, TBM is currently too demanding
      to use for daily clinical work.

PMID- 25977577
TI  - Low quality of discharge summaries for patients with poorly controlled diabetes
      on a clinical teaching unit.

PMID- 25977578
TI  - Targets of opportunity for precision medicine.

PMID- 25977579
TI  - VWF fibers induce thrombosis during cancer.

PMID- 25977580
TI  - Fibronectin: extra domain brings extra risk?

PMID- 25977581
TI  - Activating KIR: iN Kase of KIR-ligand mismatch.

PMID- 25977582
TI  - HY antibodies as biomarkers for chronic GVHD.

PMID- 25977583
TI  - von Willebrand factor fibers promote cancer-associated platelet aggregation in
      malignant melanoma of mice and humans.
AB  - Tumor-mediated procoagulatory activity leads to venous thromboembolism and
      supports metastasis in cancer patients. A prerequisite for metastasis formation
      is the interaction of cancer cells with endothelial cells (ECs) followed by their
      extravasation. Although it is known that activation of ECs and the release of the
      procoagulatory protein von Willebrand factor (VWF) is essential for malignancy,
      the underlying mechanisms remain poorly understood. We hypothesized that VWF
      fibers in tumor vessels promote tumor-associated thromboembolism and metastasis.
      Using in vitro settings, mouse models, and human tumor samples, we showed that
      melanoma cells activate ECs followed by the luminal release of VWF fibers and
      platelet aggregation in tumor microvessels. Analysis of human blood samples and
      tumor tissue revealed that a promoted VWF release combined with a local
      inhibition of proteolytic activity and protein expression of ADAMTS13 (a
      disintegrin-like and metalloproteinase with thrombospondin type I repeats 13)
      accounts for this procoagulatory milieu. Blocking endothelial cell activation by
      the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF
      networks and inhibited tumor progression in a transgenic mouse model. Our
      findings implicate a mechanism wherein tumor-derived vascular endothelial growth
      factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC
      activation envisions new therapeutic strategies attenuating tumor-related
      angiogenesis and coagulation. 

PMID- 25977586
TI  - Towards a Trans-national Industrial Hazard History: Charting the Circulation of
      Workplace Dangers, Debates and Expertise.

PMID- 25977584
TI  - Inducible caspase-9 suicide gene controls adverse effects from alloreplete T
      cells after haploidentical stem cell transplantation.
AB  - To test the feasibility of a single T-cell manipulation to eliminate
      alloreactivity while sparing antiviral and antitumor T cells, we infused 12
      haploidentical hematopoietic stem cell transplant patients with increasing
      numbers of alloreplete haploidentical T cells expressing the inducible caspase 9
      suicide gene (iC9-T cells). We determined whether the iC9-T cells produced immune
      reconstitution and if any resultant graft-versus-host disease (GVHD) could be
      controlled by administration of a chemical inducer of dimerization (CID;
      AP1903/Rimiducid). All patients receiving >10(4) alloreplete iC9-T lymphocytes
      per kilogram achieved rapid reconstitution of immune responses toward 5 major
      pathogenic viruses and concomitant control of active infections. Four patients
      received a single AP1903 dose. CID infusion eliminated 85% to 95% of circulating
      CD3(+)CD19(+) T cells within 30 minutes, with no recurrence of GVHD within 90
      days. In one patient, symptoms and signs of GVHD-associated cytokine release
      syndrome (CRS-hyperpyrexia, high levels of proinflammatory cytokines, and rash)
      resolved within 2 hours of AP1903 infusion. One patient with varicella zoster
      virus meningitis and acute GVHD had iC9-T cells present in the cerebrospinal
      fluid, which were reduced by >90% after CID. Notably, virus-specific T cells
      recovered even after AP1903 administration and continued to protect against
      infection. Hence, alloreplete iC9-T cells can reconstitute immunity
      posttransplant and administration of CID can eliminate them from both peripheral
      blood and the central nervous system (CNS), leading to rapid resolution of GVHD
      and CRS. The approach may therefore be useful for the rapid and effective
      treatment of toxicities associated with infusion of engineered T lymphocytes.
      This trial was registered at www.clinicaltrials.gov as #NCT01494103. 

PMID- 25977585
TI  - Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin
      generation.
AB  - Fibrin, the coagulation end product, consolidates the platelet plug at sites of
      vascular injury and supports the recruitment of circulating platelets. In
      addition to integrin alphaIIbbeta3, another as-yet-unidentified receptor is
      thought to mediate platelet interaction with fibrin. Platelet glycoprotein VI
      (GPVI) interacts with collagen and several other adhesive macromolecules. We
      evaluated the hypothesis that GPVI could be a functional platelet receptor for
      fibrin. Calibrated thrombin assays using platelet-rich plasma (PRP) showed that
      tissue factor-triggered thrombin generation was impaired in GPVI-deficient
      patients and reduced by the anti-GPVI Fab 9O12. Assays on reconstituted PRP and
      PRP from fibrinogen-deficient patients revealed a fibrinogen-dependent
      enhancement of thrombin generation, which relied on functional GPVI. The effect
      of GPVI was found to depend on fibrin polymerization. A binding assay showed a
      specific interaction between GPVI-Fc and fibrin, inhibited by the Fab 9O12. This
      Fab also reduced platelet adhesion to fibrin at low (300 s(-1)) and high (1500 s(
      1)) wall shear rates. Platelets adherent to fibrin displayed shape change,
      exposure of procoagulant phospholipids, and the formation of small clots. When
      hirudinated blood was perfused at 1500 s(-1) over preformed fibrin-rich clots,
      the Fab 9O12 decreased the recruitment of platelets by up to 85%. This study
      identifies GPVI as a platelet receptor for polymerized fibrin with 2 major
      functions: (1) amplification of thrombin generation and (2) recruitment of
      circulating platelets to clots. These so-far-unrecognized properties of GPVI
      confer on it a key role in thrombus growth and stabilization. 

PMID- 25977587
TI  - INDUSTRIAL RESEARCH AT THE EASTERN TELEGRAPH COMPANY, 1872-1929.
AB  - By the late nineteenth century the submarine telegraph cable industry, which had
      blossomed in the 1850s, had reached what historians regard as technological
      maturity. For a host of commercial, cultural and technical reasons, the industry
      seems to have become conservative in its attitude towards technological
      development, which is reflected in the small scale of its staff and facilities
      for research and development. This paper argues that the attitude of the cable
      industry towards research and development was less conservative and altogether
      more complex than historians have suggested. Focusing on the crucial case of the
      Eastern Telegraph Company, the largest single operator of submarine cables, it
      shows how the company encouraged inventive activity among outside and in-house
      electricians and, in 1903, established a small research laboratory where staff
      and outside scientific advisors pursued new methods of cable signalling and cable
      designs. The scale of research and development at the Eastern Telegraph Company,
      however, was small by comparison to that of its nearest competitor, Western
      Union, and dwarfed by that of large electrical manufacturers. This paper explores
      the reasons for this comparatively weak provision but also suggests that this was
      not inappropriate for a service-sector firm.

PMID- 25977589
TI  - Evaluation of particle resuspension in young children's breathing zone using
      stationary and robotic (PIPER) aerosol samplers.
AB  - Development of asthma in young children may be associated with high exposure to
      particulate matter (PM). However, typical stationary samplers may not represent
      the personal exposure of children ages 3 and younger since they may not detect
      particles resuspended from the floor as children play, thus reducing our ability
      to correlate exposure and disease etiology. To address this, an autonomous robot,
      the Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler, was
      developed to simulate the movements of children as they play on the floor. PIPER
      and a stationary sampler took simultaneous measurements of particle number
      concentration in six size channels using an optical particle counter and
      inhalable PM on filters in 65 homes in New Jersey, USA. To study particle
      resuspension, for each sampler we calculated the ratio of particle concentration
      measured while PIPER was moving to the average concentration of particles
      measured during a reference period when PIPER remained still. For all
      investigated particle sizes, higher particle resuspension was observed by PIPER
      compared to the stationary sampler. In 71% of carpeted homes a more significant
      (at the alpha = 0.05 level) resuspension of particles larger than 2.5 MUm was
      observed by PIPER compared to the stationary sampler. Typically, particles larger
      than 2.5 MUm were resuspended more efficiently than smaller particles, over both
      carpeted and bare floors. Additionally, in carpeted homes estimations of PM10
      mass from the particle number concentrations measured on PIPER while it was
      moving were on average a factor of 1.54 higher compared to reference period when
      PIPER was not moving. For comparison, the stationary sampler measured an increase
      of PM2.5 mass by a factor of only 1.08 when PIPER was moving compared to a
      reference period. This demonstrates that PIPER is able to resuspend particles
      through movement, and provide a better characterization of the resuspended
      particles than stationary samplers. Accurate measurement of resuspended PM will
      improve estimates of children's total PM exposure.

PMID- 25977588
TI  - Topical Developments in High-Field Dynamic Nuclear Polarization.
AB  - We report our recent efforts directed at improving high-field DNP experiments. We
      investigated a series of thiourea nitroxide radicals and the associated DNP
      enhancements ranging from epsilon = 25 to 82 that demonstrate the impact of
      molecular structure on performance. We directly polarized low-gamma nuclei
      including 13C, 2H, and 17O using trityl via the cross effect. We discuss a
      variety of sample preparation techniques for DNP with emphasis on the benefit of
      methods that do not use a glass-forming cryoprotecting matrix. Lastly, we
      describe a corrugated waveguide for use in a 700 MHz / 460 GHz DNP system that
      improves microwave delivery and increases enhancements up to 50%.

PMID- 25977590
TI  - The effects of mental health symptoms and marijuana expectancies on marijuana use
      and consequences among at-risk adolescents.
AB  - Based on expectancy theory, adolescents at risk for mental health symptoms, such
      as those involved in the juvenile court system, may use marijuana due to the
      belief that use will attenuate anxiety and depressive symptoms. In a diverse
      sample of youth involved in the Santa Barbara Teen Court system (N = 193), we
      examined the association between mental health symptoms and marijuana
      expectancies on marijuana use and consequences. In general, stronger positive
      expectancies and weaker negative expectancies were both associated with increased
      marijuana use. Youth that reported more symptoms of both anxiety and depression
      and stronger positive expectancies for marijuana also reported more consequences.
      We found that youth experiencing the greatest level of consequences from
      marijuana were those that reported more depressive symptoms and stronger positive
      expectancies for marijuana. Findings suggest that these symptoms, combined with
      strong positive expectancies about marijuana's effects, have implications for
      consequences among at-risk youth.

PMID- 25977591
TI  - Ultrasonic atomization of liquids in drop-chain acoustic fountains.
AB  - When focused ultrasound waves of moderate intensity in liquid encounter an air
      interface, a chain of drops emerges from the liquid surface to form what is known
      as a drop-chain fountain. Atomization, or the emission of micro-droplets, occurs
      when the acoustic intensity exceeds a liquid-dependent threshold. While the
      cavitation-wave hypothesis, which states that atomization arises from a
      combination of capillary-wave instabilities and cavitation bubble oscillations,
      is currently the most accepted theory of atomization, more data on the roles of
      cavitation, capillary waves, and even heat deposition or boiling would be
      valuable. In this paper, we experimentally test whether bubbles are a significant
      mechanism of atomization in drop-chain fountains. High-speed photography was used
      to observe the formation and atomization of drop-chain fountains composed of
      water and other liquids. For a range of ultrasonic frequencies and liquid sound
      speeds, it was found that the drop diameters approximately equalled the
      ultrasonic wavelengths. When water was exchanged for other liquids, it was
      observed that the atomization threshold increased with shear viscosity. Upon
      heating water, it was found that the time to commence atomization decreased with
      increasing temperature. Finally, water was atomized in an overpressure chamber
      where it was found that atomization was significantly diminished when the static
      pressure was increased. These results indicate that bubbles, generated by either
      acoustic cavitation or boiling, contribute significantly to atomization in the
      drop-chain fountain.

PMID- 25977592
TI  - Bayesian Semi-parametric Analysis of Semi-competing Risks Data: Investigating
      Hospital Readmission after a Pancreatic Cancer Diagnosis.
AB  - In the U.S., the Centers for Medicare and Medicaid Services uses 30-day
      readmission, following hospitalization, as a proxy outcome to monitor quality of
      care. These efforts generally focus on treatable health conditions, such as
      pneumonia and heart failure. Expanding quality of care systems to monitor
      conditions for which treatment options are limited or non-existent, such as
      pancreatic cancer, is challenging because of the non-trivial force of mortality;
      30-day mortality for pancreatic cancer is approximately 30%. In the statistical
      literature, data that arise when the observation of the time to some non-terminal
      event is subject to some terminal event are referred to as 'semi-competing risks
      data'. Given such data, scientific interest may lie in at least one of three
      areas: (i) estimation/inference for regression parameters, (ii) characterization
      of dependence between the two events, and (iii) prediction given a covariate
      profile. Existing statistical methods focus almost exclusively on the first of
      these; methods are sparse or non-existent, however, when interest lies with
      understanding dependence and performing prediction. In this paper we propose a
      Bayesian semi-parametric regression framework for analyzing semi-competing risks
      data that permits the simultaneous investigation of all three of the
      aforementioned scientific goals. Characterization of the induced posterior and
      posterior predictive distributions is achieved via an efficient Metropolis
      Hastings-Green algorithm, which has been implemented in an R package. The
      proposed framework is applied to data on 16,051 individuals diagnosed with
      pancreatic cancer between 2005-2008, obtained from Medicare Part A. We found that
      increased risk for readmission is associated with a high comorbidity index, a
      long hospital stay at initial hospitalization, non-white race, male, and
      discharge to home care.

PMID- 25977593
TI  - Evaluation of pyrrolidine and pyrazolone derivatives as inhibitors of
      trypanosomal phosphodiesterase B1 (TbrPDEB1).
AB  - Human African trypanosomiasis (HAT) is a parasitic disease, caused by the
      protozoan pathogen Trypanosoma brucei, which affects thousands every year and
      which is in need of new therapeutics. Herein we report the synthesis and
      assessment of a series of pyrrolidine and pyrazolone derivatives of human
      phosphodiesterase 4 (hPDE4) inhibitors for the assessment of their activity
      against the trypanosomal phosphodiesterase TbrPDEB1. The synthesized compounds
      showed weak potency against TbrPDEB1.

PMID- 25977594
TI  - Rumination and depression in Chinese university students: The mediating role of
      overgeneral autobiographical memory.
AB  - OBJECTIVE: In this study, we examined the mediator effects of overgeneral
      autobiographical memory (OGM) on the relationship between rumination and
      depression in 323 Chinese university students. METHOD: 323 undergraduates
      completed the questionnaires measuring OGM (Autobiographical Memory Test),
      rumination (Ruminative Response Scale) and depression (Center for Epidemiologic
      Studies Depression Scale). RESULTS: Results using structural equation modeling
      showed that OGM partially-mediated the relationship between rumination and
      depression (chi2 = 88.61, p < .01; RMSEA = .051; SRMR = .040; and CFI = .91).
      Bootstrap methods were used to assess the magnitude of the indirect effects. The
      results of the bootstrap estimation procedure and subsequent analyses indicated
      that the indirect effects of OGM on the relationship between rumination and
      depressive symptoms were significant. CONCLUSION: The results indicated that
      rumination and depression were partially mediated by OGM.

PMID- 25977595
TI  - Staff Perspectives on Juvenile Drug Court Operations: A Multi-Site Qualitative
      Study.
AB  - Substance use is pervasive among youth, particularly among those involved in the
      juvenile justice system. Juvenile drug courts (JDCs) are a promising approach for
      delinquent youth with substance abuse issues. However, research regarding JDCs
      has shown inconsistent effects, and little is known about the specific components
      associated with positive outcomes. The current study examines data from
      interviews of JDC judges and team member focus groups in six JDCs from two
      contiguous southeastern states to identify stakeholders' perceptions about what
      places youth at risk for involvement in JDC and the factors that may contribute
      to successful outcomes. In addition, we examine these stakeholders' perceptions
      of the strengths and challenges facing their JDCs. Our findings highlight the
      importance of parents and specific strategies implemented by JDCs in influencing
      the outcomes of youth in JDCs and the importance of interagency collaboration and
      access to treatment and community resources for the overall success of JDCs.

PMID- 25977596
TI  - Embryo transfer in competition horses: Managing mares and expectations.
AB  - Embryo transfer (ET) is an accepted and successful technique for obtaining foals
      from mares without interrupting their competition careers. Recent research,
      however, suggests that the potential of factors including heat, exercise,
      repeated embryo flushing and repeated manipulation of the reproductive cycle
      using exogenous hormones to have a negative impact on fertility may have been
      underestimated. This paper reviews the evidence base for involvement of these
      factors in repeated failures to recover embryos from nongeriatric competition
      mares without obvious clinical or pathological indications of reproductive
      abnormalities. It concludes that, for some mares at least, a cessation of
      exercise for the periovulatory period and the period between ovulation and embryo
      flushing, combined with careful management of flushing-induced endometritis, and
      minimal hormonal manipulation of the reproductive cycle, may be necessary to
      optimise embryo recovery rates. Mare owners may have been encouraged to request
      ET for their mares following high-profile examples in the media of elite mares
      that have produced foals by ET whilst competing. The veterinarian should educate
      mare owners about the multiple factors that may affect the chances of recovering
      an embryo from their mares, and should manage the expectations of mare owners so
      that they do not approach ET programmes in the expectation that there will be no
      disruption to their training and competition plans.

PMID- 25977597
TI  - Anti-inflammatory properties of low and high doxycycline doses: an in vitro
      study.
AB  - Doxycycline is used to treat infective diseases because of its broadspectrum
      efficacy. High dose administration (100 or 200 mg/day) is often responsible for
      development of bacterial resistances and endogenous flora alterations, whereas
      low doses (20-40 mg/day) do not alter bacteria susceptibility to antibiotics and
      exert anti-inflammatory activities. In this study, we wanted to assess the
      efficacy of both low and high doxycycline doses in modulating IL-8, TNF-alpha,
      and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental
      settings were used, differing in the timing of doxycycline treatment in respect
      to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low
      doses were more effective than high doses in modulating gene expression of LPS
      induced proinflammatory cytokines (IL-8, TNF-alpha, and IL-6), when added before
      (pretreatment) or after (posttreatment) LPS stimulation. This effect was not
      appreciated when LPS and doxycycline were simultaneously added to cell cultures:
      in this case high doses were more effective. In conclusion, our in vitro study
      suggests that low doxycycline doses could be safely used in chronic or acute skin
      diseases in which the inflammatory process, either constantly in progress or
      periodically recurring, has to be prevented or controlled.

PMID- 25977598
TI  - Differential mucin expression by respiratory syncytial virus and human
      metapneumovirus infection in human epithelial cells.
AB  - Mucins (MUC) constitute an important component of the inflammatory and innate
      immune response. However, the expression of these molecules by respiratory viral
      infections is still largely unknown. Respiratory syncytial virus (RSV) and human
      metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause
      severe low respiratory tract disease in infants and young children worldwide.
      Currently, there is not vaccine available for neither virus. In this work, we
      explored the differential expression of MUC by RSV and hMPV in human epithelial
      cells. Our data indicate that the MUC expression by RSV and hMPV differs
      significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21,
      and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was
      dominated by the infection with hMPV. These results may contribute to the
      different immune response induced by these two respiratory viruses. 

PMID- 25977599
TI  - Sustained interleukin-1beta exposure modulates multiple steps in glucocorticoid
      receptor signaling, promoting split-resistance to the transactivation of
      prominent anti-inflammatory genes by glucocorticoids.
AB  - Clinical treatment with glucocorticoids (GC) can be complicated by cytokine
      induced glucocorticoid low-responsiveness (GC-resistance, GCR), a condition
      associated with a homogeneous reduction in the expression of GC-receptor- (GR-)
      driven anti-inflammatory genes. However, GR level and phosphorylation changes
      modify the expression of individual GR-responsive genes differently. As sustained
      IL-1beta exposure is key in the pathogenesis of several major diseases with
      prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven
      genes in cells cultured in IL-1beta and afterwards challenged with GC. After a GC
      challenge, sustained IL-1beta exposure reduced the cytoplasmic GR level,
      GR(Ser203) and GR(Ser211) phosphorylation, and GR nuclear translocation and led
      to selective GCR in the expression of the studied genes. Compared to GC alone, in
      a broad range of GC doses plus sustained IL-1beta, FKBP51 mRNA expression was
      reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast,
      high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was
      increased by 5-fold. These effects were cytokine-selective, IL-1beta dose- and IL
      1R1-dependent. The integrated gain and loss of gene functions in the "split GCR"
      model may provide target cells with a survival advantage by conferring resistance
      to apoptosis, chemotherapy, and GC. 

PMID- 25977600
TI  - Chemokine-ligands/receptors: multiplayers in traumatic spinal cord injury.
AB  - Spinal cord injury (SCI) results in complex posttraumatic sequelae affecting the
      whole neuraxis. Due to its involvement in varied neuromodulatory processes, the
      chemokine-ligand/receptor-network is a key element of secondary lesion cascades
      induced by SCI. This review will provide a synopsis of chemokine-ligand/receptor
      expression along the whole neuraxis after traumatic spinal cord (sc) insults on
      basis of recent in vivo and in vitro findings in a SCI paradigm of thoracic force
      defined impact lesions (Infinite Horizon Impactor) in adult rats. Analyses of
      chemokine-ligand/receptor-expression at defined time points after sc lesion of
      different severity grades or sham operation revealed that these inflammatory
      mediators are induced in distinct anatomical sc regions and in thalamic nuclei,
      periaqueductal grey, and hippocampal structures in the brain. Cellular and
      anatomical expression profiles together with colocalization/expression of neural
      stem/progenitor cell markers in adult sc stem cells niches or with pain-related
      receptors and mediators in dorsal horns, dorsal columns, and pain-processing
      brain areas support the notion that chemokines are involved in distinct cascades
      underlying clinical posttraumatic impairments and syndromes. These aspects and
      their implication in concepts of tailored SCI treatment are reviewed in the
      context of the recent literature on chemokine-ligand/receptor involvement in
      complex secondary lesion cascades. 

PMID- 25977601
TI  - Neutrophils induced licensing of natural killer cells.
AB  - Natural killer (NK) cells acquire effector function through a licensing process
      and exert anti-leukemia/tumor effect. However, there is no means to promote a
      licensing effect of allogeneic NK cells other than cytomegalovirus reactivation
      induced licensing in allogeneic hematopoietic stem cell transplantation in human.
      In mice, a licensing process is mediated by Ly49 receptors which recognize self
      major histocompatibility complex class I. The distribution of four Ly49 receptors
      showed similar pattern in congenic mice, B10, B10.BR, and B10.D2, which have B10
      background. Forty Gy-irradiated 2 * 10(6) B10.D2 cells including splenocytes,
      peripheral blood mononuclear cells in untreated mice, or granulocyte colony
      stimulating factor treated mice were injected intraperitoneally into B10 mice. We
      found that murine NK cells were effectively licensed by intraperitoneal injection
      of donor neutrophils with its corresponding NK receptor ligand in B10 mice as a
      recipient and B10.D2 as a donor. Mechanistic studies revealed that NK cells
      showed the upregulation of intracellular interferon-gamma and CD107a expression
      as markers of NK cell activation. Moreover, enriched neutrophils enhanced
      licensing effect of NK cells; meanwhile, licensing effect was diminished by
      depletion of neutrophils. Collectively, injection of neutrophils induced NK cell
      licensing (activation) via NK receptor ligand interaction. 

PMID- 25977602
TI  - Static third-harmonic lines in widely variable fiber continuum generation.
AB  - An intriguing phenomenon of third-harmonic generation under fiber continuum
      generation is the emission of an anharmonic signal. One popular interpretation of
      this effect has developed into a general theory of fiber third-harmonic
      generation. Here we produce "static" third-harmonic Unes dictated fully by fiber
      properties independent of pump parameters, in contrast to the signals of all
      known phase-matched nonlinear optical processes that vary dynamically with these
      parameters. We argue that the anharmonic signal is an illusion of the continuum
      generation, that it is in fact harmonic, and that this theory should be
      reevaluated.

PMID- 25977603
TI  - Public Engagement Through Shared Immersion: Participating in the Processes of
      Research.
AB  - Recently, the literature has emphasized the aims and logistics of public
      engagement, rather than its epistemic and cultural processes. In this conceptual
      article, we use our work on surgical simulation to describe a process that has
      moved from the classroom and the research laboratory into the public sphere. We
      propose an innovative shared immersion model for framing the relationship between
      engagement activities and research. Our model thus frames the public engagement
      experience as a participative encounter, which brings visitor and researcher
      together in a shared (surgical) experience mediated by experts from a range of
      domains.

PMID- 25977604
TI  - Do females behave differently in COPD exacerbation?
AB  - INTRODUCTION: Little is known about whether there is any sex effect on chronic
      obstructive lung disease (COPD) exacerbations. This study is intended to describe
      the possible sex-associated differences in exacerbation profile in COPD patients.
      METHODS: A total of 384 COPD patients who were hospitalized due to exacerbation
      were evaluated retrospectively for their demographics and previous and current
      exacerbation characteristics. RESULTS: The study was conducted on 109 (28%)
      female patients and 275 (72%) male patients. The mean age was 68.30+/-10.46
      years. Although females had better forced expiratory volume in 1 second and near
      normal forced vital capacity, they had much impaired arterial blood gas levels
      (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon
      dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001), indicating severe
      exacerbation with respiratory failure. More females had two exacerbations and two
      hospitalizations, while more men had one exacerbation and one hospitalization.
      Low adherence to treatment and pulmonary embolism were more frequent in females.
      Females had longer time from the onset of symptoms till the admission and longer
      hospitalization duration than males. Comorbidities were less in number and
      different in women (P<0.05). Women were undertreated and using more oral
      corticosteroids. CONCLUSION: Current data showed that female COPD patients might
      be more prone to have severe exacerbations, a higher number of hospitalizations,
      and prolonged length of stay for hospitalization. They have a different
      comorbidity profile and might be undertreated for COPD.

PMID- 25977605
TI  - Inter-alpha-trypsin inhibitor heavy chain 4: a novel biomarker for environmental
      exposure to particulate air pollution in patients with chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease
      that is correlated with environmental stress. Particulate matter <=10 MUm (PM10)
      is considered to be a risk factor for COPD development; however, the effects of
      PM10 on the protein levels in COPD remain unclear. Fifty subjects with COPD and
      15 healthy controls were recruited. Gene ontology analysis of differentially
      expressed proteins identified immune system process and binding as the most
      important biological process and molecular function, respectively, in the
      responses of PM10-exposed patients with COPD. Biomarkers for PM10 in COPD were
      identified and compared with the same in healthy controls and included
      proteoglycan 4 (PRG4), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), and
      apolipoprotein F (APOF). PRG4 and ITIH4 were associated with a past 3-year PM10
      exposure level. The receiver operating characteristic curve analysis showed that
      ITIH4 is a sensitive and specific biomarker for PM10 exposure (area under the
      curve [AUC] =0.690, P=0.015) compared with PRG4 (AUC =0.636, P=0.083), APOF (AUC
      =0.523, P=0.766), 8-isoprostane (AUC =0.563, P=0.405), and C-reactive protein
      (CRP; AUC =0.634, P=0.086). ITIH4 levels were correlated with CRP (r=0.353,
      P=0.005), suggesting that ITIH4 may be involved in an inflammatory mechanism. In
      summary, serum ITIH4 may be a PM10-specific biomarker in COPD and may be related
      to inflammation. 

PMID- 25977606
TI  - Comparing the effects of negative and mixed emotional messages on predicted
      occasional excessive drinking.
AB  - In this work we present two types of emotional message, negative (sadness) versus
      mixed (joy and sadness), with the aim of studying their differential effect on
      attitude change and the probability estimated by participants of repeating the
      behavior of occasional excessive drinking in the near future. The results show
      that for the group of participants with moderate experience in this behavior the
      negative message, compared to the mixed one, is associated with higher
      probability of repeating the risk behavior and a less negative attitude toward
      it. These results suggest that mixed emotional messages (e.g. joy and sadness
      messages) could be more effective in campaigns for the prevention of this risk
      behavior. 

PMID- 25977608
TI  - Benefits, risks, and safety of external beam radiation therapy for breast cancer.
AB  - Breast cancer is a common and complex disease often necessitating multimodality
      care. Breast cancer may be treated with surgical resection, radiotherapy (RT),
      and systemic therapy, including chemotherapy, hormonal therapy, and targeted
      therapies, or a combination thereof. In the past 50 years, RT has played an
      increasingly significant role in the treatment of breast cancer, resulting in
      improvements in locoregional control and survival for women undergoing mastectomy
      who are at high risk of recurrence, and allowing for breast conservation in
      certain settings. Although radiation provides significant benefit to many women
      with breast cancer, it is also associated with risks of toxicity, including
      cardiac and pulmonary toxicity, lymphedema, and secondary malignancy. RT
      techniques have advanced and continue to evolve dramatically, offering increased
      precision and reproducibility of treatment delivery and flexibility of treatment
      schedule. This increased sophistication of RT offers promise of improved outcomes
      by maintaining or improving efficacy, reducing toxicity, and increasing patient
      access and convenience. A review of the role of radiation therapy in breast
      cancer, its associated toxicities and efforts in toxicity reduction is presented.

PMID- 25977609
TI  - Prescription of potentially inappropriate medication in older persons in
      Switzerland: does the dispensing channel make a difference?
AB  - BACKGROUND: Drugs can be supplied either directly from the prescribing physician
      (physician dispensing [PD]) or via a pharmacy. It is unclear whether the
      dispensing channel is associated with quality problems. Potentially inappropriate
      medication (PIM) is associated with adverse outcomes in older persons and can be
      considered a marker for quality deficits in prescribing. We investigated whether
      prevalence of PIM differs across dispensing channels. PATIENTS AND METHODS: We
      analyzed basic health insurance claims of 50,747 person quarter years with PIM
      use of residents of the Swiss cantons Aargau and Lucerne of the years 2012 and
      2013. PIM was identified using the Beers 2012 criteria and the PRISCUS list. We
      calculated PIM prevalence stratified by supply channel. Adjusted mixed effects
      logistic regression analysis was done to estimate the effect of obtaining
      medications through the dispensing physician as compared to the pharmacy channel
      on receipt of PIM. The most frequent PIMs were identified. RESULTS: There is a
      small but detectable difference in total PIM prevalence: 30.7% of the population
      supplied by a dispensing physician as opposed to 29.3% individuals who received
      medication in a pharmacy. According to adjusted logistic regression individuals
      who obtained the majority of their medications from their prescribing physician
      had a 15% higher chance to receive a PIM (odds ratio 1.15, 95% confidence
      interval 1.08-1.22; P<0.001). CONCLUSION: Physician dispensing seems to affect
      quality and safety of drug prescriptions. Quality issues should not be neglected
      in the political discussion about the regulations on PD. Future studies should
      explore whether PD is related to other indicators of inefficiency or quality
      flaws. The present study also underlines the need for interventions to reduce the
      high rates of PIM prescribing in Switzerland.

PMID- 25977611
TI  - A preliminary inventory of the catfishes of the lower Rio Nhamunda, Brazil
      (Ostariophysi, Siluriformes).
AB  - The Rio Nhamunda is a poorly-known clearwater river draining the southern Guiana
      Shield of Brazil. In this study we report the findings of a preliminary
      ichthyological survey, focusing on catfishes (Siluriformes). We identify a total
      of 36 species (31 genera, seven families) from the Nhamunda, including 11 species
      already recorded from the river. Overall, our survey results show that even rapid
      surveys can provide important information on Amazon fish biodiversity, suggesting
      potential new species, providing range extensions for nominal species, and
      additionally highlighting taxa in need of taxonomic revision and genetic study.
      As well as the traditional forms of data collected on biodiversity surveys (i.e.
      preserved specimen vouchers), our study also provides "new" types of data in the
      form of DNA barcodes and images of fishes exhibiting colouration in life,
      information that will be invaluable in future work addressing difficult groups. O
      Rio Nhamunda e um rio de agua clara, pouco conhecido, que drena parte do Escudo
      das Guianas em territorio brasileiro. Nesse estudo, nos reportamos os resultados
      de um levantamento ictiofaunistico preliminar dessa area, tendo como foco os
      bagres (Siluriformes). Nos identificamos um total de 36 especies (31 generos,
      sete familias) provenientes de nossa coleta, e adicionamos 11 especies ja
      conhecidas para o rio. De maneira geral, os resultados de nossa pesquisa mostram
      que mesmo levantamentos rapidos podem gerar informacoes importantes sobre a
      biodiversidade de peixes amazonicos, sugerindo potenciais especies novas,
      ampliando a area de distribuicao de especies, alem de apontar a necessidade de
      revisoes taxonomicas e estudos geneticos para alguns taxa. Para alem das formas
      tradicionais de dados coletados em pesquisas de biodiversidade (i.e. especimes
      preservados), nosso estudo fornece "novas" formas de dados, como DNA barcodes e
      imagens com o padrao de coloracao dos especimes vivos, informacoes essas que
      serao de valor inestimavel para futuros estudos que abordem grupos taxonomicos
      dificeis. 

PMID- 25977610
TI  - Profile of efraloctocog alfa and its potential in the treatment of hemophilia A.
AB  - Hemophilia care has improved dramatically over the past 50 years, evolving from
      plasma concentrates, to purified plasma proteins, to recombinant clotting
      factors. These collective developments allowed for home delivery of on-demand and
      prophylactic treatment, resulting in the reduction of hemophilia morbidity and
      mortality and improved quality of life. Although efficacious in treating
      bleeding, conventional factor products' half-lives require frequent venipuncture,
      which remains a significant burden to patients. Despite the remarkable advances
      in hemophilia care, no improvements have, until now, been made to the
      pharmacokinetic properties of factor products. Multiple strategies have more
      recently been employed to generate novel bioengineered products that, with great
      hope, represent the next wave of progress in hemophilia care. The use of these
      products will undoubtedly raise important discussion about choosing conventional
      factor over new long-acting factor products. Incorporation of these therapies
      into clinical care is accompanied by unanswered safety questions that will likely
      be evaluated only in postmarketing surveillance analysis. Further, these products
      may change current treatment paradigms with unclear cost repercussions and
      feasibility. This paper will review efraloctocog alfa (FVIII-Fc) and its role in
      the treatment of hemophilia A. 

PMID- 25977612
TI  - A new record of Potamanthellus caenoides Ulmer 1939 (Ephemeroptera:
      Neoephemereidae) from the southern Western Ghats of India.
AB  - BACKGROUND: As part of ongoing exploration of the mayflies of hill streams of the
      southern Western Ghats of India, we establish a new record of mayfly. NEW
      INFORMATION: Potamanthellus caenoides Ulmer 1939 is newly recorded based on
      larval collection from the upstream of Silent Valley National Park of the
      southern Western Ghats. Brief ecological notes are appended.

PMID- 25977613
TI  - Bumble Bees (Hymenoptera: Apidae: Bombus spp.) of Interior Alaska: Species
      Composition, Distribution, Seasonal Biology, and Parasites.
AB  - BACKGROUND: Despite the ecological and agricultural significance of bumble bees
      in Alaska, very little is known and published about this important group at the
      regional level. The objectives of this study were to provide baseline data on
      species composition, distribution, seasonal biology, and parasites of the genus
      Bombus at three major agricultural locations within Alaska: Fairbanks, Delta
      Junction, and Palmer, to lay the groundwork for future research on bumble bee
      pollination in Alaska. NEW INFORMATION: A total of 8,250 bumble bees representing
      18 species was collected from agricultural settings near Delta Junction,
      Fairbanks, and Palmer, Alaska in 2009 and 2010. Of the 8,250 specimens, 51% were
      queens, 32.7% were workers, and 16.2% were males. The species composition and
      relative abundances varied among sites and years. Delta Junction had the highest
      relative abundance of bumble bees, representing 51.6% of the specimens collected;
      the other two locations, Fairbanks and Palmer represented 26.5% and 21.8% of the
      overall catch respectively. The species collected were: BombusbohemicusSeidl 1837
      (= B.ashtoni (Cresson 1864)), B.balteatusDahlbom 1832, B.bifariusCresson 1878,
      B.centralisCresson 1864, B.cryptarum (Fabricius 1775) (=B.moderatusCresson 1863),
      B.distinguendusMorawitz 1869, B.flavidusEversmann 1852 (=B.fernaldaeFranklin
      1911), B.flavifronsCresson 1863, B.frigidusSmith 1854, B.insularis (Smith 1861),
      B.jonellus (Kirby 1802), B.melanopygusNylander 1848, B.mixtusCresson 1878,
      B.neoboreusSladen 1919, B.occidentalisGreene 1858, B.perplexusCresson 1863,
      B.rufocinctusCresson 1863, and B.sylvicolaKirby 1837. Overall, the most common
      bumble bees near agricultural lands were B.centralis, B.frigidus, B.jonellus,
      B.melanopygus, B.mixtus, and B.occidentalis. Species' relative population
      densities and local diversity were highly variable from year to year.
      Bombusoccidentalis, believed to be in decline in the Pacific Northwest states,
      represented 10.4% of the overall specimens collected from the three sites
      studied. Bumble bees were found to be infected by Nosema and nematodes with
      infection rates up to 2.1% and 16.7% respectively. Of the eight species infected
      by parasites, B.occidentalis displayed the highest Nosema infection, while
      B.centralis was the species with the highest infection of nematodes. To our
      knowledge this represents the first multi-year study on bumble bees from the main
      agricultural areas of Alaska to provide baseline data on species composition,
      distribution, seasonal biology, and parasites of the genus Bombus.

PMID- 25977614
TI  - The Eight Stages of Trust and "Amanah" in Medicine and the Dunning-Kruger effect.
AB  - The Dunning-Kruger effect is a cognitive bias in which unskilled people make poor
      decisions and reach erroneous conclusions, but their incompetence denies them the
      metacognitive ability to recognise their mistakes. These unskilled people
      therefore suffer from illusory superiority, rating their ability as above
      average, much higher than it actually is, while the highly skilled underrate
      their own abilities, suffering from illusory inferiority. 

PMID- 25977615
TI  - Searching for the Origin through Central Nervous System: A Review and Thought
      which Related to Microgravity, Evolution, Big Bang Theory and Universes, Soul and
      Brainwaves, Greater Limbic System and Seat of the Soul.
AB  - Cerebrospinal fluid (CSF) serves buoyancy. The buoyancy thought to play crucial
      role in many aspects of the central nervous system (CNS). Weightlessness is
      produced mainly by the CSF. This manuscript is purposely made to discuss its
      significance which thought contributing towards an ideal environment for the CNS
      to develop and function normally. The idea of microgravity environment for the
      CNS is supported not only by the weightlessness concept of the brain, but also
      the noted anatomical position of the CNS. The CNS is positioned in bowing
      position (at main cephalic flexure) which is nearly similar to an astronaut in a
      microgravity chamber, fetus in the amniotic fluid at early gestation, and animals
      and plants in the ocean or on the land. Therefore, this microgravity position can
      bring us closer to the concept of origin. The hypothesis on 'the origin' based on
      the microgravity were explored and their similarities were identified including
      the brainwaves and soul. Subsequently a review on soul was made. Interestingly,
      an idea from Leonardo da Vinci seems in agreement with the notion of seat of the
      soul at the greater limbic system which has a distinctive feature of "from God
      back to God". 

PMID- 25977607
TI  - Hepatitis infection in the treatment of opioid dependence and abuse.
AB  - Many new and existing cases of viral hepatitis infections are related to
      injection drug use. Transmission of these infections can result directly from the
      use of injection equipment that is contaminated with blood containing the
      hepatitis B or C virus or through sexual contact with an infected individual. In
      the latter case, drug use can indirectly contribute to hepatitis transmission
      through the dis-inhibited at-risk behavior, that is, unprotected sex with an
      infected partner. Individuals who inject drugs are at-risk for infection from
      different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B
      virus infection also face additional risk should they become co-infected with
      hepatitis D virus. Protection from the transmission of hepatitis viruses A and B
      is best achieved by vaccination. For those with a history of or who currently
      inject drugs, the medical management of viral hepatitis infection comprising
      screening, testing, counseling and providing care and treatment is evolving.
      Components of the medical management of hepatitis infection, for persons
      considering, initiating, or receiving pharmacologic therapy for opioid addiction
      include: testing for hepatitis B and C infections; education and counseling
      regarding at-risk behavior and hepatitis transmission, acute and chronic
      hepatitis infection, liver disease and its care and treatment; vaccination
      against hepatitis A and B infection; and integrative primary care as part of the
      comprehensive treatment approach for recovery from opioid abuse and dependence.
      In addition, participation in a peer support group as part of integrated medical
      care enhances treatment outcomes. Liver disease is highly prevalent in patient
      populations seeking recovery from opioid addiction or who are currently receiving
      pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not
      a contraindication to evaluation, care, or treatment of liver disease due to
      hepatitis virus infection. Successful pharmacotherapy for opioid addiction
      stabilizes patients and improves patient compliance to care and treatment
      regimens as well as promotes good patient outcomes. Implementation and
      integration of effective hepatitis prevention programs, care programs, and
      treatment regimens in concert with the pharmacological therapy of opioid
      addiction can reduce the public health burdens of hepatitis and injection drug
      use. 

PMID- 25977616
TI  - Effect of C-peptide Alone or in Combination with Nicotinamide on Glucose and
      Insulin Levels in Streptozotocin-Nicotinamide-Induced Type 2 Diabetic Mice.
AB  - BACKGROUND: Both C-peptide and nicotinamide are known to reduce blood glucose in
      type 1 diabetes. In the present study, the effects of C-peptide alone or in
      combination with nicotinamide on glucose and insulin levels in streptozotocin
      nicotinamide-induced type 2 diabetic mice. METHODS: The study used 70 adult male
      NMARI mice, weighing 25-35 g, divided into seven groups: control; type 1
      diabetic; type 2 diabetic; type 2 diabetic + C-peptide; type 2 diabetic +
      nicotinamide; type 2 diabetic + nicotinamide and C-peptide; type 2 diabetic +
      glyburide. Type 2 diabetes was induced with ip injection of streptozotocin
      nicotinamide. Twenty eight days after the onset of diabetes, treatment with C
      peptide, nicotinamide, nicotinamide + C-peptide, or glyburide were initiated.
      Glucose and insulin levels were evaluated. One-way ANOVA and Least Significant
      Difference (LSD) tests were used to test for significance. RESULTS: Blood glucose
      significantly increased (P < 0.001) in all diabetic mice compared with control
      mice. Insulin resistance and blood glucose levels were significantly reduced (P <
      0.05) in C-peptide and nicotinamide + C-peptide mice compared with type 2
      diabetic mice. CONCLUSION: The present study supports the anti-diabetic effects
      of C-peptide, nicotinamide + C-peptide, and suggests that one of the anti
      diabetic mechanisms of these compounds is mediated through the reduction of
      insulin resistance.

PMID- 25977617
TI  - Accessory Spleen: Prevalence and Multidetector CT Appearance.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence and computed
      tomography (CT) appearances of accessory spleens in hospital-based patients, and
      to measure and make comparisons between accessory spleen size and density.
      METHODS: A cross-sectional study was carried out in a diagnostic center in Erbil,
      Iraq during January-December, 2012. Biphasic abdominal CT images of 334
      consecutive patients with different age groups were evaluated for the presence of
      an accessory spleen, and if identified, it was further analysed for shape,
      diameter, density, number, and location. Patients with inadequate CT techniques,
      splenectomy, hematological disorders, and widespread lesions in the abdomen were
      excluded from this study. RESULTS: Of the 334 patients (198 female, 136 male),
      with a mean age of 47.2 years (SD 15.7), 82 accessory spleens were detected in 63
      patients (18.8%). Their mean diameter was 14.7 mm (range 3-79 mm), 68% were round
      in shape and 75.6% were medial to the main spleen. Sixty percent of the cases
      showed a single accessory spleen and 40% had more than one (up to 4 detected). A
      significant difference in the mean diameter of accessory spleens between similar
      and different densities than the main spleen was observed (P = 0.018), 71
      accessory spleens (mean diameter = 15.97 mm) displayed similar densities to the
      main spleen, while 11 (mean diameter = 7.09 mm) were hypodense or hyperdense to
      the main spleen. CONCLUSION: The prevalence of an accessory spleen is high, and
      should be considered by radiologists during abdominal CT scan reporting.

PMID- 25977618
TI  - Incidence of Jaundice in Plasmodium vivax Malaria: A Prospective Study in
      Moodabidri, South India.
AB  - BACKGROUND: A prospective study was taken to look for the incidence of jaundice
      in Plasmodium vivax malaria patients in Moodabidri, a coastal town of South
      India. METHODS: A prospective study was conducted in the patients admitted with
      the diagnosis of Plasmodium vivax malaria at the Alva's health centre, during
      study period 1st Jun 2011 to 10th October 2012. Bilirubin levels were checked in
      all the selected patients. Patients who had their total bilirubin level 3.0 mg%
      or more were considered to be having jaundice and were further tested for anemia
      and hepatic dysfunction by carrying out hemoglobin (Hb), serum glutamic
      oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT),
      surface antigen of the hepatitis B virus (HBsAg). The data collected were
      analysed statistically. RESULTS: A total of 188 patients who had Plasmodium vivax
      malaria as diagnosed by peripheral blood film (PBF) and rapid diagnostic test
      (RDT) were included in the study. Jaundice was present in 19 (10.1%) patients and
      the mean (SD) level of serum bilirubin was 4.5 mg/dL (2.4) (maximum = 12.7 mg %)
      with 94.7% (n = 18) of the patients having predominantly indirect type or
      unconjugated hyperbilirubinemia. The hepatic dysfunction was present in 15
      (78.9%) with mean (SD) level of aspartate aminotransferase (AST) was 61.57 IU/L
      (SD 33.8) (maximum = 160 IU/L) and alanine aminotransferase (ALT) was 54.8 IU/L
      (SD 21.2) (maximum = 108 IU/L). Anemia was present in 3 (15.8%) patients and the
      mean hemoglobin level was 12.8 gm/dL (SD 1.8) (minimum = 6.4 gm/dL). Out of 19
      patients who had jaundice majority were males (94.7 %, n = 18) and only one
      female (5.3%, n = 1) was found to be having jaundice. The age of the patients who
      had jaundice ranged from 17 to 60 years 29 years (SD 13.7). CONCLUSION: This
      study has further reiterated the fact that Plasmodium vivax malaria is no longer
      a "benign" disease and it can also produce jaundice, hepatic dysfunction, and
      anemia.

PMID- 25977619
TI  - An outcome of Surgically Treated Head and Neck Cancer in one of the tertiary
      Referral Center in the East Coast of Malaysia: A 6-year Retrospective Analysis.
AB  - BACKGROUND: Surgical management of head and neck cancer is undoubtedly
      challenging, and we would like to see the outcome of managing such cases at one
      of the tertiary referral center in the East Coast of Malaysia. METHODS: A 6-year
      retrospective analysis of surgically treated head and neck cancer cases in
      Hospital Tengku Ampuan Afzan (HTAA) Kuantan, Pahang was conducted. RESULTS: The
      total number of patients reviewed was 55 and mean age of the patients was 59
      years (SD 12). The larynx was the most common surgically treated site (29.1%),
      followed by the oral cavity (16.4%) and the paranasal sinuses (14.5%). Majority
      of the patients presented with stage III (32.8%) and stage IV (41.8%) cancer.
      Post-operative local complications (23.6%) and wound breakdown was identified as
      the most common cause (20%). Low hemoglobin level prior to surgery was associated
      with anemia after surgery (P = 0.007) and prolonged hospital stay (P = 0.030).
      Tumor recurrence was observed in 21.8% of the cases. Advanced stage tumor had
      more percentage of positive margin than early stage tumor i.e., 23% in early
      stage versus 58% in advanced stage (P = 0.050). CONCLUSION: Surgical management
      of head and neck cancer in this center has an acceptable outcome.

PMID- 25977620
TI  - Warfarin Therapy: Survey of Patients' Knowledge of their Drug Regimen.
AB  - BACKGROUND: Warfarin is utilised for the treatment of thromboembolic disease. Its
      use demands a careful and continual monitoring given its narrow therapeutic index
      and potentially life-threatening complications. The aim of this study was to
      assess the extent of patients' knowledge of their warfarin therapy. METHODS: A
      total of 200 consecutive patients from a single community hospital completed an
      online survey questionnaire (www.eSurveysPro.com). Using the responses to the
      questionnaire, we recorded compliance to warfarin therapy, knowledge about drug
      interactions, adverse effects of warfarin therapy, complications, and resulting
      hospitalisation. RESULTS: We recruited 200 patients, 55% (109/200) women and 45%
      (91/200) men, among which 88% were compliant with their daily medication. Of the
      200 patients, 56% were unaware of any potential drug interactions, 58% were
      unaware of any adverse effects, 27% had experienced adverse effects, 12% had been
      hospitalised because of adverse effects (33% of which were due to bleeding), and
      65% kept a personal record of their international normalised ratio. CONCLUSION:
      Despite the high level of compliance, patient knowledge of warfarin therapy was
      low. Given the potential drug interactions and complexities involved with
      warfarin therapy, it is of high importance that medical professionals educate
      their patients and make them aware of any impending signs of emergent medical
      complications.

PMID- 25977621
TI  - A Psychometric Properties of the Malay-version Police Stress Questionnaire.
AB  - BACKGROUND: Police Stress Questionnaire (PSQ) was developed to measure police
      specific stressors. The present study was the first to have translated the PSQ to
      Malay. This study aims to test the reliability, construct validity, and component
      structure of the Malay-version PSQ. METHODS: A set of survey consisted of the
      Malay-version PSQ, General Health Questionnaire (GHQ-12), Job Content
      Questionnaire (JCQ), Global Stress Questionnaire (GSQ) and General Self-rated
      Health (GSRH) were distributed to 300 traffic police officers in Kuala Lumpur and
      all traffic police officers in a few districts of Pahang and Negeri Sembilan.
      RESULTS: The response rate was 65.5% (N = 262). The reported Cronbach's alpha
      coefficient was 0.93 for Operational PSQ (PSQ-Op) and 0.94 for Organisational PSQ
      (PSQ-Org). Findings indicated that the PSQ had positive construct validity with
      the GSRH, GSQ, and GHQ. After excluding four factors related to lifestyles, all
      police-specific stressors were highly loaded (0.50) in one component. CONCLUSION:
      It is confirmed that the Malay-version PSQ, excluding the four factors related to
      lifestyle, was uni-dimensional, reliable, and a valid questionnaire. This study
      proffers a potentially better instrument for assessing the stressors among
      Malaysian police.

PMID- 25977622
TI  - Posterior Capsule Rupture during Phacoemulsification among Patients with
      Pseudoexfoliation-Is There A Correlation?
AB  - This study was done to correlate the occurrence of posterior capsule rupture
      among patients with pseudoexfoliation during phacoemulsification. This was a
      retrospective audit of patients who underwent phacoemulsification type cataract
      surgery from January 2011 to December 2012 in a tertiary hospital in Malaysia.
      Data was obtained from the National Eye Database (NED) of Malaysia. The data was
      analysed using SPSS version 21.0. By using logistic regression analysis, it was
      found that there was no significant increase in the occurrence of posterior
      capsule rupture among patients with pseudoexfoliation. Hence, we concluded that
      there was no correlation between the occurrence of posterior capsule rupture and
      the presence of pesudoexfoliation among patients who underwent
      phacoemulsification. 

PMID- 25977623
TI  - Aggressive Digital Papillary Adenocarcinoma-A rare Entity Posing a Diagnostic
      Challenge.
AB  - Aggressive digital papillary adenocarcinoma (ADPCA) is rare tumor of the sweat
      glands, which is characterised by lesions on the fingers, toes and the digits.
      The lesion is serious but often overlooked because it is confused clinically with
      benign and non-tumorous entities. In this paper, we present an interesting case
      of ADPCA in a 40-year-old lady, suspected clinically as pyogenic granuloma, with
      the initial excision biopsy indicating a malignant tumor in the sweat gland. Ray
      amputation of the affected finger was done followed by a thorough work up to rule
      out metastasis. Histopathological features were studied in detail, along with
      required markers. We present this case as the documentation of this malignant
      tumor is limited in literature and also it requires a high index of suspicion
      when dealing with all masses arising on the digits. 

PMID- 25977624
TI  - A paralabral cyst of the hip joint causing sciatica: case report and review of
      literature.
AB  - The prolapse of the intervertebral disc is most common cause of sciatica; rare
      causes of sciatica are pelvic fractures, pelvic tumors, piriformis syndrome, a
      rupture of medial head of gastronemius and sacroiliac joint dysfunction. We
      report the case of a 30-year-old male with a paralabral cyst of the hip joint
      with an acetabular labral tear causing sciatica. Our patient had an acetabular
      labral tear caused by a repetitive micro-trauma and external rotation injury. The
      diagnosis of the paralabral cyst with acetabular labral tear was based on
      clinical examination and histopathological examinations, and Magnetic resonance
      imaging findings. The patient underwent successful surgical excision of
      paralabral cyst and surgical repair of an acetabular labral tear. The present
      case reinforces the need for clinicians to be vigilant about rare causes of
      sciatica. 

PMID- 25977625
TI  - Second-trimester uterine rupture: lessons learnt.
AB  - Uterine rupture is a rare life-threatening complication. It mainly occurs in the
      third trimester of pregnancy and is rarely seen during the first or second
      trimesters. Our centre experienced three important cases of uterine rupture.
      FIRST CASE: spontaneous uterine rupture at 14 weeks of pregnancy, which was
      diagnosed at autopsy. It was misled by the ultrasound finding of an intrauterine
      pregnancy, and searching for other non-gynaecological causes delayed the urgent
      obstetric surgical management. SECOND CASE: ruptured uterus at 24 weeks following
      medical termination due to foetal anomaly. It was diagnosed only at laparotomy
      indicated for failed medical termination and chorioamnionitis. Third case:
      uterine rupture at 21 weeks of pregnancy in a patient with gastroenterology
      symptoms. In these reports, we have discussed the various risk factors,
      presentations, course of events and difficulties in diagnosing uterine rupture.
      The study concludes that the clinical presentation of uterine ruptures varies. It
      occurs regardless of gestational age. Ultrasound findings of intrauterine
      pregnancy with free fluid do not exclude uterine rupture or ectopic pregnancy.
      Searching for non-gynaecological causes in such clinical presentations might
      delay crucial surgical intervention, which leads to unnecessary morbidity,
      mortality or loss of obstetrics function.

PMID- 25977626
TI  - A case of right upper abdominal pain misdiagnosed on computerized tomography.
AB  - Right upper abdominal pain is a common symptom in patients presenting to surgery
      emergency. Most of these cases can be diagnosed accurately on clinical evaluation
      or imaging. We report an unusual case of right upper abdominal pain, which could
      not be diagnosed correctly pre-operatively despite using various imaging
      modalities. 

PMID- 25977627
TI  - Intraoperative fluorescence angiography for cerebrovascular neurosurgery in
      universiti sains malaysia.

PMID- 25977629
TI  - Comparison of nested polymerase chain reaction and microscopy as diagnostic tools
      in congenital malaria: a study at tjark corneile hillers hospital maumere,
      indonesia.
AB  - BACKGROUND: Microscopic detection is the conventional method for detecting
      malaria parasites. Although it is efficient and inexpensive, it has its
      limitations. In recent years, polymeras chain reaction (PCR) has been considered
      superior to microscopy in detecting mixed Plasmodium infections or infections
      with low parasite density. To determine whether microscopic or nested PCR (nPCR)
      is better at detecting congenital malaria (CM). METHODS: Blood smear examination
      and nPCR were performed with blood samples taken from mothers and their newborns,
      who were likely to be suffering from CM and in whom one of the symptoms was low
      birth weight (LBW). The sensitivity and specificity of each method were then
      compared. RESULTS: During one year of study, the prevalence of CM among 92 LBW
      newborns was determined to be 6.8% using microscopy and 7.8% using nPCR. Among
      the 92 mother-infant paired subjects, CM was detected in 34 subjects (37%) by
      microscopy and in 39 subjects (42.4%) by nPCR. nPCR was more sensitive (76.5% vs
      66.7%) but less specific (77.6% vs 84.9%) than microscopy. When the two methods
      were compared, nPCR gave significantly better results in diagnosing CM (AUC =
      0.770; P < 0.001). CONCLUSION: Although microscopy remains the most appropriate
      method for the diagnosis of CM in remote areas, nPCR can be considered a
      complementary test.

PMID- 25977628
TI  - Neural Commitment of Embryonic Stem Cells through the Formation of Embryoid
      Bodies (EBs).
AB  - An embryonic stem cell (ESC) is a good tool to generate neurons in vitro and can
      be used to mimic neural development in vivo. It has been widely used in research
      to examine the role of cell signalling during neuronal development, test the
      effects of drugs on neurons, and generate a large population of functional
      neurons. So far, a number of protocols have been established to promote the
      differentiation of ESCs, such as direct and indirect differentiation. One of the
      widely used protocols to generate neurons is through the spontaneous formation of
      multicellular aggregates known as embryonic bodies (EBs). However, for some, it
      is not clear why EB protocol could be the protocol of choice. EB also is known to
      mimic an early embryo; hence, knowing the similarities between EB and an early
      embryo is essential, particularly the information on the players that promote the
      formation of EBs or the aggregation of ESCs. This review paper focuses on these
      issues and discusses further the generation of neural cells from EBs using a well
      known protocol, the 4-/4+ protocol. 

PMID- 25977630
TI  - Transorbital sonographic measurement of normal optic sheath nerve diameter in
      nigerian adult population.
AB  - BACKGROUND: The optic nerve covering is elastic enough to allow a detectable
      enlargement in response to changes in intracranial pressure. The objective of the
      present study was to determine the optic nerve sheath diameter (ONSD) in normal
      Nigerian adults. METHODS: This study was conducted on 400 healthy adults. The
      ONSD was measured at 3 mm posterior to the globe using a 7.5 MHz linear
      transducer. RESULTS: The study population consisted of 192 males and 208 females
      with mean age of 36.94 years (SD 16.63). The range of values for ONSD was 3.36 to
      5.1 mm. The median right ONSD was 4.110 with a range of 3.36-4.86 mm (mean: 4.18
      mm (SD 0.49)), while the median left ONSD was 4.35 mm with a range of 3.77-5.10
      mm (mean: 4.17 + mm (SD 0.44)). No statistically significant variation in ONSD
      was found between the right and left sides (P = 0.12) and also between male and
      female participants (P = 0.296 and 0.745 for the respective right and left ONSD).
      CONCLUSION: The normal reference values of ONSD measurements in adults were
      obtained. It showed no significant correlation with side (right and left), age,
      and sex. Furthermore, there is no significant correlation of ONSD with the body
      height and weight.

PMID- 25977631
TI  - Relationship between Intracellular Magnesium Level, Lung Function, and Level of
      Asthma Control in Children with Chronic Bronchial Asthma.
AB  - BACKGROUND: This study aimed to determine the intracellular (red blood cell
      (RBC)) magnesium levels in children with chronic bronchial asthma and to
      determine the relationship between the magnesium level and peak expiratory flow
      rate (PEFR), type of asthma treatment, and level of asthma control. METHODS: A
      cross-sectional study was conducted at the Paediatric Clinic, Sarawak General
      Hospital. A total of 100 children, aged 6-12 years with chronic bronchial asthma,
      were recruited according to the study criteria. Venous blood samples were
      obtained to measure the intracellular (RBC) magnesium level using the GBC Avanta
      Flame Atomic Absorption Spectrophotometer. RESULTS: Mean age was 8.57 (SD 1.18)
      years, and 63% of the participants were male. Mean duration of asthma was 62.2
      (SD 32.3) months. A normal intracellular magnesium level was found in 95% of the
      participants, with a mean of 2.27 (SD 0.33) mmol/L. Two-thirds of the
      participants had a normal peak flow expiratory rate (> 80% of predicted value).
      About 85% were using both reliever and controller. Almost half of the
      participants (49%) had chronic asthma that was well-controlled. No significant
      relationship was found between magnesium level and age (r = -0.089, P = 0.379),
      gender (t = 0.64, P = 0.52), duration of asthma (r = -0.03, P = 0.74), PEFR (t =
      0.41, P = 0.68), current level of asthma control (t = 0.02, P = 0.97), and
      current treatment (t = 0.414, P = 0.680). CONCLUSION: There was no significant
      intracellular magnesium deficiency in children with chronic bronchial asthma.
      There was no significant relationship between therapeutic medications used for
      treatment of children with chronic asthma and intracellular magnesium levels.

PMID- 25977632
TI  - An empirical approach to the diagnosis and treatment of cerebrospinal fluid
      rhinorrhoea: an optimised method for developing countries.
AB  - BACKGROUND: We aimed to test a new approach for repairing cerebrospinal fluid
      (CSF) leaks and to determine the demographic, diagnostic, and treatment factors
      associated with the successful management of intracranial complication. Owing to
      the high frequency of endoscopic surgeries and the low cost of medical care in
      Iran, we decided to report our experience of reconstruction after CSF leaks.
      METHODS: We retrospectively reviewed our experience in the diagnosis and
      management of CSF rhinorrhoea in Iran between 2005 and 2012. The locations of all
      pre-repair leaks were identified using simple, readily available methods. The
      follow-up time ranged from 2 to 72 months. RESULTS: Of the 37 participants, 59.5%
      were men and the mean age was 33 years. The success rate was 86.1%, and the most
      common aetiological factor was trauma (57%). The most common location was the
      ethmoidal fovea (45.9%), followed by the sphenoid sinus (24.3%), the cribriform
      plate (13.5%), and the posterior table of the frontal sinus (5.4%). CONCLUSION:
      Medical care in Iran has considerable budget restrictions. This study advocates a
      practical method of treatment for patients in similar circumstances, with a
      success rate of 86.1% when compared to the 90.6% achieved with other techniques.
      KEYWORDS: cerebrospinal fluid leak, endoscopic, intracranial pressure ICP.

PMID- 25977633
TI  - Improving Breast Cancer Preventive Behavior among Female Medical Staff: The Use
      of Educational Intervention based on Health Belief Model.
AB  - BACKGROUND: Breast cancer is one of the most common types of cancer prevalent
      among women worldwide. Preventive behaviors such as early diagnosis through
      screening tests play an important role in prevention and control of the disease.
      This study aimed to determine the effects of educational intervention using a
      health belief model on breast cancer preventive behaviors. METHODS: This
      interventional study was conducted on 130 female employees of Zahedan University
      of Medical Sciences who were randomly divided into intervention and control
      groups. A questionnaire, made and validated by the researcher, was completed
      before and one month after training by the study subjects. Data were analysed
      using regression analysis, independent sample T-test, chi-square and Pearson's
      correlation coefficient using the SPSS software 18. RESULTS: There were
      significant changes in the training group, following educational intervention in
      the awareness construct and in some constructs of the model including perceived
      susceptibility, perceived benefits, and perceived barriers, as well as in
      practice compared to the control group (P < 0.05). Nevertheless, perceived
      barriers remained as the only predictor in the model, such that for every unit
      increase in this variable, the behavior score increased by 18%. CONCLUSION: The
      use of educational intervention based on Health Belief Model had positive effect
      on knowledge of breast cancer preventive behaviors among participants.

PMID- 25977634
TI  - Validation of the Malay Version of the Parental Bonding Instrument among
      Malaysian Youths Using Exploratory Factor Analysis.
AB  - BACKGROUND: Parenting behaviour is culturally sensitive. The aims of this study
      were (1) to translate the Parental Bonding Instrument into Malay (PBI-M) and (2)
      to determine its factorial structure and validity among the Malaysian population.
      METHODS: The PBI-M was generated from a standard translation process and
      comprehension testing. The validation study of the PBI-M was administered to 248
      college students aged 18 to 22 years. RESULTS: Participants in the comprehension
      testing had difficulty understanding negative items. Five translated double
      negative items were replaced with five positive items with similar meanings.
      Exploratory factor analysis showed a three-factor model for the PBI-M with
      acceptable reliability. Four negative items (items 3, 4, 8, and 16) and item 19
      were omitted from the final PBI-M list because of incorrect placement or low
      factor loading (< 0.32). Out of the final 20 items of the PBI-M, there were 10
      items for the care factor, five items for the autonomy factor and five items for
      the overprotection factor. All the items loaded positively on their respective
      factors. CONCLUSION: The Malaysian population favoured positive items in
      answering questions. The PBI-M confirmed the three-factor model that consisted of
      care, autonomy and overprotection. The PBI-M is a valid and reliable instrument
      to assess the Malaysian parenting style. Confirmatory factor analysis may further
      support this finding. KEYWORDS: Malaysia, parenting, questionnaire, validity.

PMID- 25977635
TI  - The dangers of couching in southwest Nigeria.
AB  - The need to highlight the dangers to the eye and visual status in couching has
      become necessary in order to discourage its patronage. This was a bi-center
      clinic-based prospective descriptive study about new cases of couched eyes which
      were seen over a two-year period. Oral interviews, eye examinations, refractions,
      and perimetry tests were used to obtain the information. SPSS version 16 was used
      for the descriptive analysis. Twenty-five patients and 30 eyes of 15 (60%) males
      and 10 (40%) females were studied. The age range was 34-90 years with a mean age
      of 67.87 years (SD 11.27). Presenting versus (vs) corrected visual acuity (VA)
      for normal vision was 6.7% vs 23.3%, visual impairment was 16.7% vs 26.3%, and
      blindness was 76.7% vs 50%. A significant number still remained blind after
      corrections (P = 0.014). The most common presenting complaint was "poor/blurred
      vision" in 24 (80.4%) and the most frequent duration of couching before
      presentation was 7-12 months (46.7%). Subjects with a cup:disc ratio > 0.6 had
      intraocular pressures (IOPs) of > 21 mmHg, and 50% of those patients had IOP > 40
      mmHg (P = 0.001). Glaucoma (13.3%) and corneal opacity/retinal
      detachment/couching maculopathy/optic atrophy (10%) were the most common
      complications. Couching causes visually-disabling complications, and is therefore
      strongly condemned. Increasing public awareness and putting a policy in place for
      affordable and accessible cataract services in government hospitals would
      gradually phase out its patronage. 

PMID- 25977636
TI  - Primary breast angiosarcoma: pathological and radiological diagnosis.
AB  - Primary breast angiosarcoma is a very rare aggressive mesenchymal tumor, which
      may represent only 0.04% of all breast malignant tumors. We report a case of
      primary angiosarcoma in the breast of a 22-year-old woman who presented with a
      mass in her right breast. Ultrasonography revealed a large heterogeneous
      lobulated mass lesion consistent with a fibroadenoma or phyllodes tumor. After a
      period of six months, she presented with nipple retraction, so a core needle
      biopsy was performed. Histopathology revealed a well differentiated angiosarcoma
      (grade I/III), but in the mastectomy specimen, numerous neoplastic multinucleated
      giant cells were evident, which resembled those found in other sarcomas, such as
      malignant fibrous histiocytoma or extra skeletal osteogenic sarcoma, and this
      caused difficulty making the diagnosis. Using immunohistochemical (IHC) studies,
      neoplastic cells were positively stained for CD31, CD34, and factor VIII-related
      antigens, which confirmed that the tumor was a high grade, poorly differentiated
      angiosarcoma (grade III/III). In conclusion, angiosarcomas may have different
      grade patterns in the same tumor, and as a result it is necessary to examine the
      whole tumor for definite grading. Imaging findings in angiosarcomas are non
      specific, therefore they may misdiagnosed, frequently by other benign lesions. 

PMID- 25977637
TI  - Anomalous Bilateral Communication between the Inferior Alveolar Nerve and the
      Auriculotemporal Nerve: A Rare Variation.
AB  - Branches of the posterior division of the mandibular nerve show various anomalous
      communications in the infratemporal region. Understanding such communication has
      relevance in the management of neuropathies and surgical procedures in this
      region. This study was conducted to explore such communicating branches,
      anticipating that they might provide information of clinical significance. A
      total of 15 human cadavers (30 infratemporal regions) were studied to explore
      such communicating branches in infratemporal region. The branches of the
      posterior division of the mandibular nerve were carefully dissected, and these
      branches were studied and analysed for any abnormal course. In one case, a rare
      type of bilateral communication between the auriculotemporal nerve and the
      inferior alveolar nerve, forming a loop with no association with any structure,
      was observed. It is possible that such communicating branches may be associated
      with delayed regression of the first arch vessels. The clinical implications of
      these anomalous communications require further detailed study for improved
      management of neuropathies and surgical procedures. 

PMID- 25977638
TI  - Incidental Follicular Thyroid Carcinoma Detected on F-18 FDG PET CT Imaging for
      Breast Cancer Staging: A Case Report.
AB  - The detection rate of thyroid incidentalomas is increasing; in fact, as many as
      2.3% of patients undergoing FDG PET-CT for other indications have been found to
      have thyroid incidentalomas. The risk of malignancy in these thyroid
      incidentalomas can be as high as 47%. The increased uptake and the focal uptake
      pattern of F-18 fluorodeoxyglucose (FDG) in the thyroid during positron emission
      tomography (PET)-computed tomography (CT), and the calcification of the thyroid
      incidentaloma, are associated with even higher risk of malignancy. We report a
      case of a lady undergoing FDG PET-CT for breast cancer staging but noted to have
      a calcified thyroid incidentaloma, which was proven to be follicular thyroid
      carcinoma. 

PMID- 25977639
TI  - Atypical Clival Chordoma in an Adolescent without Imaging Evidence of Bone
      Involvement.
AB  - Clival chordoma is a rare primary bone tumour that arises from the remnant of the
      notochord and typically occurs in older adults. Upon imaging, the tumour can be
      seen arising from the clivus and causes clival destruction. This usually provides
      insight for a diagnosis. Here we present a case of a non-enhancing, pre-pontine
      mass that was hypointense on T1W and hyperintense on T2W in an adolescent. No
      clival bone erosion was observed. Based on the age group, imaging findings, and
      lack of clival erosion, a provisional diagnosis of epidermoid cyst was made and
      the tumour was resected. This patient was eventually diagnosed with a clival
      chordoma based on histopathological examination. 

PMID- 25977640
TI  - Career development expectations and challenges of midwives in Urban Tanzania: a
      preliminary study.
AB  - BACKGROUND: Approaches to addressing the shortage of midwives are a great need
      especially in Sub-Saharan Africa including Tanzania. The midwifery shortage in
      Tanzania consists of two major causes; the first is the shortage of pre-service
      nursing training and the second is the low rate of retention as it is difficult
      to sustain midwives' career motivations. Lack of opportunities for career
      development, is one of the most related problems to keep midwives motivated.
      Continuing education as an approach to career development can heighten midwives'
      motivation and cultivate more skilled midwives who can educate other midwives or
      students and who could raise the status of midwives. Effective continuing
      education is ongoing, interactive, contextually relevant and based on needs
      assessment, however there is very limited research that describes Tanzanian
      midwives perspective of expectations for career development; hence this research
      is significant for revealing important and meaningful professional desires of
      midwives in Tanzania. METHODS: This was a preliminary qualitative study, using
      snowball sampling to recruit 16 midwives in Tanzania. The researchers used a semi
      structured interview including probing questions with both a focus group and
      several individuals. The data were collected from July to December 2013 and coded
      into categories and sub-categories. RESULTS: There were 14 midwives in the focus
      group interview and two midwives in the individual interviews. Through data
      analysis, four major categories (with subcategories) emerged: (1) motivation for
      learning (to achieve the MDGs, and to raise reproductive health), (2) knowledge
      is power (to provide good practice based on knowledge, to be a role model,
      knowledge gives higher position and courage, and knowledge enables one to
      approach to the government), (3) there is no end to learning (hunger for
      learning, and ripple effect). CONCLUSIONS: From findings, four major categories
      plainly showed midwives' desire for learning, however they experienced a number
      of barriers to access further education. Continuing education is one of the most
      important and effective ways to cultivate and retain midwives. In order to
      respond to the midwives expectations and challenges to overcome the barriers
      inherent in providing more continuing education, it will be necessary to increase
      accessible opportunities for career development in Tanzania.

PMID- 25977641
TI  - Assessing the impact of academic-practice partnerships on nursing staff.
AB  - BACKGROUND: The 'spillover effect' of academic-practice partnerships on hospital
      nursing staff has received limited attention. In 2007, the Department of Veterans
      Affairs (VA) created the VA Nursing Academy (VANA) to fund fifteen partnerships
      between schools of nursing and local VA healthcare facilities. In this paper, we
      examine the experiences of the VA staff nurses who worked on the units used for
      VANA clinical training. METHODS: We used survey methods to collect information
      from staff nurses at all active VANA sites on their characteristics, exposure to
      the program's clinical training activities, satisfaction with program components,
      and perspectives of the impact on their work and their own plans for education (N
      = 314). Our analyses utilized descriptive statistics and bivariate and
      multivariate regression. RESULTS: Results show that staff nurses working on VANA
      units had moderately high levels of exposure to the program's clinical education
      activities, and most reported positive experiences with those activities. The
      vast majority (80 %) did not perceive the presence of students as making their
      work more difficult. Among those who were enrolled or considering enrolling in a
      higher education program, over a quarter (28 %) said that their VA's
      participation in VANA had an influence on this decision. The majority of staff
      nurses were generally satisfied with their experience with the students. Their
      satisfaction with the program was related to the level or dose of their exposure
      to it. Those who were more involved were more satisfied. Greater interaction with
      the students, more information on the program, and a preceptor role were all
      independently associated with greater program satisfaction. CONCLUSIONS: Our
      study suggests that academic-practice partnerships may have positive spillover
      effects on staff nurses who work on clinical education units. Further,
      partnerships may be able to foster positive experiences for their unit nurses by
      focusing on informing and engaging them in clinical training activities. In
      particular, our results suggest that academic-practice partnerships should keep
      unit nurses well informed about program content and learning objectives,
      encourage frequent interaction with students, involve them in partnership-related
      unit-based activities, and urge them to become preceptors for the students.

PMID- 25977642
TI  - Learning transitions-a descriptive study of nurses' experiences during advanced
      level nursing education.
AB  - BACKGROUND: Building capacity in a changing health care system is a challenge for
      advanced nursing education programs. Master-level nursing education is
      increasingly becoming the required education level for specialist nurses, and
      additional studies are needed to learn more about students' experiences and
      learning transitions while undertaking such education. This study aimed to
      explore nursing students' experience of their learning transitions while
      undertaking advanced nursing education and to describe how they translated the
      new knowledge and competence they gained into clinical practice. METHODS: We used
      a qualitative research design with narrative self-reported reflections. 34 nurses
      (95 % women) from both urban and rural areas working with children, with adults
      in outpatient and inpatient endocrinology clinics in hospitals or with adults,
      including older people, attending primary health care services participated in
      the study. We collected data at two time points 15 months apart. Time one was the
      first week of the advanced nursing education, and time two was the completion of
      the education program. We used Malterud's modification of Giorgi's
      phenomenological analysis, otherwise known as systematic text condensation, to
      analyze the data. RESULTS: Two core themes captured the participants'
      experiences. The first theme was "assessing the situation of people with diabetes
      from a different perspective", with the subthemes "an expanded perspective of
      practice and higher level of reflection", "applying critical thinking in
      practice" and "changing patient-nurse relationships in diabetes care". The second
      core theme was "a change in participants' perception of their professional
      position", with the subthemes "a greater knowledge base enhancing professional
      confidence" and "a more equal position within the professional team".
      CONCLUSIONS: The study provides in-depth information about transition into
      advanced nursing education and can inform curriculum developers, nurse educators,
      policy-makers and nursing managers about how nursing education broadened
      participants' perspectives of nursing and enhanced their confidence and
      professional position.

PMID- 25977644
TI  - A highly efficient flexible dye-sensitized solar cell based on nickel
      sulfide/platinum/titanium counter electrode.
AB  - A composite film of nickel sulfide/platinum/titanium foil (NiS/Pt/Ti) with low
      cost and high electrocatalytic activity was synthesized by the use of an in situ
      electropolymerization route and proposed as a counter electrode (CE) catalyst for
      flexible dye-sensitized solar cells (FDSSCs). The FDSSC with the NiS/Pt/Ti CE
      exhibited a comparable power conversion efficiency of 7.20% to the FDSSC with the
      platinum/titanium (Pt/Ti) CE showing 6.07%. The surface morphology of the
      NiS/Pt/Ti CE with one-dimensional (1D) structure is characterized by using the
      scanning electron microscopy (SEM). The NiS/Pt/Ti CE also displayed multiple
      electrochemical functions of excellent conductivity, great electrocatalytic
      ability for iodine/triiodine, and low charge transfer resistance of 2.61 +/- 0.02
      Omega cm(2), which were characterized by using the cyclic voltammetry (CV),
      electrochemical impedance spectroscopy (EIS), and Tafel polarization plots. The
      photocurrent-photovoltage (J-V) character curves were further used to calculate
      the theoretical optical light performance parameters of the FDSSCs. It may be
      said that the NiS/Pt/Ti counter electrode is a promising catalytic material to
      replace the expensive platinum in FDSSCs. 

PMID- 25977645
TI  - Spectroellipsometric characterization and modeling of plasmonic diamond-like
      carbon nanocomposite films with embedded Ag nanoparticles.
AB  - Diamond-like carbon nanocomposite films with embedded silver nanoparticles are
      considered experimentally (spectroellipsometric characterization) and
      theoretically (modeling of optical properties). Metallic nanocomposite films were
      synthesized by reactive magnetron sputtering and were studied by transmission
      electron microscope (TEM) and atomic force microscope (AFM). The optical
      constants of the films were determined from spectroscopic ellipsometry
      measurements and were modeled using the Maxwell-Garnett approximations.
      Comparison between the extended and renormalized Maxwell-Garnett theory was
      conducted. Surface plasmon resonance peak have been found to be strongly
      dependent on the shape of nanoparticles and interaction between them. 

PMID- 25977643
TI  - MicroRNA-378-5p suppresses cell proliferation and induces apoptosis in colorectal
      cancer cells by targeting BRAF.
AB  - MicroRNAs (miRNAs) are a group of small non-coding RNA molecules that potentially
      play a critical role in tumorigenesis. Increasing evidences indicate that miR-378
      5p is dysregulated in numerous human cancers including colorectal cancer (CRC)
      which hypothesizes that miR-378-5p may play an important role in tumorigenesis.
      However, its role in CRC carcinogenesis remains poorly defined because of lacking
      target genes information. In the present study, it was demonstrated that the
      expression of miR-378-5p was down-regulated in CRC tissues and cell lines as
      determined by quantitative reverse transcription-polymerase chain reaction (qRT
      PCR). Furthermore, overexpression of miR-378-5p suppressed cell proliferation, as
      indicated by CCK-8 assay. Flow cytometric analysis demonstrated that
      overexpression of miR-378-5p induced cell cycle arrest and promoted apoptosis in
      CRC cells. A luciferase reporter assay indicated that BRAF was a direct target of
      miR-378-5p. Western blot and qRT-PCR analysis indicated that BRAF was
      significantly down-regulated by miR-378-5p in CRC cells. Moreover, miR-378-5p was
      negatively associated with BRAF in CRC tissues compared to adjacent non-tumor
      tissues. These results demonstrate that down-regulation of miR-378-5p promotes
      CRC cells growth by targeting BRAF and restoration of their levels is a
      potentially promising therapeutic in CRC. 

PMID- 25977646
TI  - The impact of ultra-low amounts of amino-modified MMT on dynamics and properties
      of densely cross-linked cyanate ester resins.
AB  - ABSTRACT: Thermostable nanocomposites based on densely cross-linked cyanate ester
      resins (CER), derived from bisphenol E and doped by 0.01 to 5 wt. % amino
      functionalized 2D montmorillonite (MMT) nanoparticles, were synthesized and
      characterized using Fourier transform infrared (FTIR), transmission electron
      microscopy (TEM), energy dispersive X-ray spectroscopy (EDXS), wide-angle X-ray
      diffraction (WAXD), dynamic mechanical analysis (DMA), differential scanning
      calorimetry (DSC), thermogravimetric analysis (TGA), far-infrared (Far-IR), and
      creep rate spectroscopy (CRS) techniques. It was revealed that ultra-low
      additives, e.g., 0.025 to 0.1 wt. %, of amino-MMT nanolayers covalently embedded
      into SER network exerted an anomalously large impact on its dynamics and
      properties resulting, in particular, in some suppression of dynamics, increasing
      the onset of glass transition temperature by 30 degrees  to 40 degrees  and
      twofold rise of modulus in temperature range from 20 degrees C to 200 degrees C.
      Contrarily, the effects became negligibly small or even negative at increased
      amino-MMT contents, especially at 2 and 5 wt. %. That could be explained by
      TEM/EDXS data displaying predominance of individual amino-MMT nanolayers and
      their thin (2 to 3 nanolayers) stacks over more thick tactoids (5 to 10
      nanolayers) and the large amino-MMT aggregates (100 to 500 nm in thickness)
      reversing the composite structure produced with increasing of amino-MMT content
      within CER matrix. The revealed effect of ultra-low amino-MMT content testifies
      in favor of the idea about the extraordinarily enhanced long-range action of the
      'constrained dynamics' effect in the case of densely cross-linked polymer
      networks. PACS: 82.35.Np Nanoparticles in polymers; 81.05.Qk Reinforced polymers
      and polymer-based composites; 81.07.Pr Organic-inorganic hybrid nanostructures.

PMID- 25977648
TI  - Thin film encapsulation for organic light-emitting diodes using inorganic/organic
      hybrid layers by atomic layer deposition.
AB  - A hybrid nanolaminates consisting of Al2O3/ZrO2/alucone (aluminum alkoxides with
      carbon-containing backbones) grown by atomic layer deposition (ALD) were reported
      for an encapsulation of organic light-emitting diodes (OLEDs). The electrical Ca
      test in this study was designed to measure the water vapor transmission rate
      (WVTR) of nanolaminates. We found that moisture barrier performance was improved
      with the increasing of the number of dyads (Al2O3/ZrO2/alucone) and the WVTR
      reached 8.5 * 10(-5) g/m(2)/day at 25 degrees C, relative humidity (RH) 85%. The
      half lifetime of a green OLED with the initial luminance of 1,500 cd/m(2) reached
      350 h using three pairs of the Al2O3 (15 nm)/ZrO2 (15 nm)/alucone (80 nm) as
      encapsulation layers. 

PMID- 25977647
TI  - Primary human nasal epithelial cell response to titanium surface with a
      nanonetwork structure in nasal implant applications.
AB  - In nasal reconstruction applications, the response of cells to titanium (Ti)
      implants is largely determined by the surface characteristics of the implant.
      This study investigated an electrochemical anodization surface treatment intended
      to improve the response of primary human nasal epithelial cells (HNEpC) to Ti
      surfaces in nasal implant applications. We used a simple and fast electrochemical
      anodization treatment, i.e., applying anodic current, to produce a titanium
      dioxide (TiO2) nanonetwork layer on the Ti surface with average lateral pore size
      below 100 nm, depending on the current applied. The TiO2 nanonetwork layer
      exhibited enhanced hydrophilicity and protein adsorption ability compared with
      untreated Ti surfaces. In addition, the spreading morphology, cytoskeletal
      arrangement, and proliferation of HNEpC on the nanonetwork layer indicated
      excellent cell response characteristics. This research advances our understanding
      regarding the means by which a TiO2 nanonetwork layer can improve the response of
      HNEpC to Ti surfaces in nasal implant applications. 

PMID- 25977649
TI  - Thermal analysis of Al + 0.1% CNT ribbon.
AB  - The objective of this work is a dilatometric study of Al + 0.1% of multiwall
      carbon nanotubes nanocomposite material (NCM) in three directions: X - parallel
      to the rolling direction; Y - perpendicular to the rolling direction and (Z)
      perpendicular to the ribbon plane. NCM specimens were made in the form of a 0.1
      mm-thick ribbon. The temperature range used for measurements was 20 degrees C to
      600 degrees C. The obtained results show that presence of nanotubes affects the
      thermal expansion coefficient (TEC) measured in different directions. alphax(T)
      and alphay(T) - TEC plots as a function of temperature along X and Y directions,
      respectively - have substantially the same shape and overlap in the area of 400
      degrees C. The expansion along X-axis becomes greater than along Y-axis below
      this temperature value. It is clear that the coefficient alphaz(T) is lower than
      alphax(T) and alphay(T) over the entire temperature range. The expansion along Z
      axis is smaller compared to that along X- and Y-axes. This behaviour suggests
      that there is a strong interatomic interaction along this direction (Z).
      alphaz(T) becomes monotonous and constant and is equal to 8 * 10(-6) degrees C(
      1) at temperatures above 300 degrees C. Such order of magnitude had not been
      obtained in earlier studies of aluminium alloys. The obtained TEC shows high
      anisotropy, which grows with the increase of temperature. The heat flow
      (differential scanning calorimetry, (DSC)) of Al + 0.1% carbon nanotubes (CNT)
      NCM is more intense compared to that of pure aluminium produced in similar
      conditions. The two representative curves have similar shape and are almost
      entirely overlapped. The thermogravimetry results confirm those of DSC. The Raman
      spectrum of this nanomaterial shows that intensity of G and D bonds is
      significantly increased compared to that of the pure material. The infrared
      diagram also confirms that in this case the mentioned bonds are more intensive
      NCM. The tensile strength measurements (sigmaB) of the studied NCM also
      demonstrate that its value increases from 140 +/- 10 MPa for Al without nanotubes
      to 200 +/- 10 MPa for NCM. 

PMID- 25977650
TI  - Nano- and mesoscale modeling of cement matrix.
AB  - Atomistic simulations of cementitious material can enrich our understanding of
      its structural and mechanical properties, whereas current computational
      capacities restrict the investigation length scale within 10 nm. In this context,
      coarse-grained simulations can translate the information from nanoscale to
      mesoscale, thus bridging the multi-scale investigations. Here, we develop a
      coarse-grained model of cement matrix using the concept of disk-like building
      block. The objective is to introduce a new method to construct a coarse-grained
      model of cement, which could contribute to the scale-bridging issue from
      nanoscale to mesoscale. PAC codes: 07.05.Tp, 62.25.-g, 82.70.Dd. 

PMID- 25977651
TI  - One-dimensional carbon nanotube@barium titanate@polyaniline multiheterostructures
      for microwave absorbing application.
AB  - Multiple-phase nanocomposites filled with carbon nanotubes (CNTs) have been
      developed for their significant potential in microwave attenuation. The
      introduction of other phases onto the CNTs to achieve CNT-based heterostructures
      has been proposed to obtain absorbing materials with enhanced microwave
      absorption properties and broadband frequency due to their different loss
      mechanisms. The existence of polyaniline (PANI) as a coating with controllable
      electrical conductivity can lead to well-matched impedance. In this work, a one
      dimensional CNT@BaTiO3@PANI heterostructure composite was fabricated. The
      fabrication processes involved coating of an acid-modified CNT with BaTiO3
      (CNT@BaTiO3) through a sol-gel technique followed by combustion and the formation
      of CNT@BaTiO3@PANI nanohybrids by in situ polymerization of an aniline monomer in
      the presence of CNT@BaTiO3, using ammonium persulfate as an oxidant and HCl as a
      dopant. The as-synthesized CNT@BaTiO3@PANI composites with heterostructures were
      confirmed by various morphological and structural characterization techniques, as
      well as conductivity and microwave absorption properties. The measured
      electromagnetic parameters showed that the CNT@BaTiO3@PANI composites exhibited
      excellent microwave absorption properties. The minimum reflection loss of the
      CNT@BaTiO3@PANI composites with 20 wt % loadings in paraffin wax reached -28.9 dB
      (approximately 99.87% absorption) at 10.7 GHz with a thickness of 3 mm, and a
      frequency bandwidth less than -20 dB was achieved from 10 to 15 GHz. This work
      demonstrated that the CNT@BaTiO3@PANI heterostructure composite can be
      potentially useful in electromagnetic stealth materials, sensors, and electronic
      devices. 

PMID- 25977652
TI  - 10-W pulsed operation of substrate emitting photonic-crystal quantum cascade
      laser with very small divergence.
AB  - High-power broad area substrate emitting photonic-crystal distributed feedback
      (DFB) quantum cascade lasers (QCLs) emitting around 4.73 MUm is reported. Two
      dimensional centered rectangular photonic-crystal (CRPC) grating is introduced to
      enhance optical coherence in large area device. Main lobe far-field radiation
      pattern with a very small divergence angle of about 0.65 degrees  * 0.31 degrees 
      is obtained. A record peak output power for vertical emitting QCLs exceeding 10 W
      is obtained with high reflectivity (HR) coating. Robust single longitudinal mode
      emission with a side mode suppression ratio (SMSR) of 30 dB is continuously
      tunable by the heat sink temperature up to 65 degrees C. 

PMID- 25977653
TI  - The effect of cyclic martensitic transformations on diffusion of cobalt atoms in
      Fe-18wt.%Mn-2wt.%Si alloy.
AB  - Diffusion characteristics of cobalt atoms were investigated using radioactive
      isotope method in phase-hardened Fe-18wt.%Mn-2wt.%Si alloy. The observed
      significant increase of diffusion coefficient of cobalt atoms under the cyclic
      gamma-epsilon-gamma martensitic transformations was due to the action of two
      independent mechanisms - an athermal one and a thermally activated one. The first
      one arose from the direct gamma-epsilon and the reverse epsilon-gamma
      transformations with corresponding direct and reverse lattice shears during
      alternating stresses and simultaneous lattice restructuring. Another mechanism
      arose under the diffusion annealing of the phase-hardened alloy. 

PMID- 25977654
TI  - Facile synthesis of composition-tuned ZnO/Zn x Cd1-x Se nanowires for
      photovoltaic applications.
AB  - ZnO/Zn x Cd1-x Se coaxial nanowires (NWs) have been successfully synthesized by
      combining chemical vapor deposition with a facile alternant physical deposition
      method. The shell composition x can be precisely tuned in the whole region (0 <=
      x <= 1) by adjusting growth time ratio of ZnSe to CdSe. As a result, the
      effective bandgaps of coaxial nanowires were conveniently modified from 1.85 eV
      to 2.58 eV, almost covering the entire visible spectrum. It was also found that
      annealing treatment was in favor of forming the mixed crystal and improving
      crystal quality. An optimal temperature of 350 degrees C was obtained according
      to our experimental results. Additionally, time resolved photo-luminescence
      spectra revealed the longest carrier lifetime in ZnO/CdSe coaxial nanowires. As a
      result, the ZnO/CdSe nanowire cell acquired the maximal conversion efficiency of
      2.01%. This work shall pave a way towards facile synthesis of ternary alloys for
      photovoltaic applications. 

PMID- 25977655
TI  - Novel thin-GaN LED structure adopted micro abraded surface to compare with
      conventional vertical LEDs in ultraviolet light.
AB  - In this study, novel thin-GaN-based ultraviolet light-emitting diodes (NTG-LEDs)
      were fabricated using wafer bonding, laser lift-off, dry etching, textured
      surface, and interconnection techniques. Placing PN electrodes on the same side
      minimized the absorption caused by electrodes in conventional vertical injection
      light-emitting diodes (V-LEDs) and the current spreading was improved. The light
      output power (700 mA) of the NTG-LEDs was enhanced by 18.3% compared with that of
      the V-LEDs, and the external quantum efficiency (EQE) of the NTG-LEDs was also
      relatively enhanced by 20.0% compared with that of a reference device. When the
      current operations were 1,500 mA, the enhancements of the light output power and
      EQE were 27.4% and 27.2%, respectively. Additionally, the efficiency droop was
      improved by more than 15% at the same current level. 

PMID- 25977656
TI  - Surfactant-treated graphene covered polyaniline nanowires for supercapacitor
      electrode.
AB  - Surfactant-treated graphene/polyaniline (G/PANI) nanocomposites were prepared by
      the MnO2 template-aided oxidative polymerization of aniline (ANI) on the
      surfactant-treated graphene sheets. The electrochemical performances of the
      G/PANI nanocomposites in a three-electrode system using an aqueous sulfuric acid
      as an electrolyte exhibited a specific capacitance of 436 F g(-1) at 1 A g(-1),
      which is much higher than the specific capacitance of pure PANI (367 F g(-1)).
      Such a higher specific capacitance of the G/PANI nanocomposite inferred an
      excellent synergistic effect of respective pseudocapacitance and electrical
      double-layer capacitance of PANI and graphene. 

PMID- 25977657
TI  - Reliable synthesis of self-running Ga droplets on GaAs (001) in MBE using RHEED
      patterns.
AB  - Self-running Ga droplets on GaAs (001) surfaces are repeatedly and reliably
      formed in a molecular beam epitaxial (MBE) chamber despite the lack of real-time
      imaging capability of a low-energy electron microscope (LEEM) which has so far
      dominated the syntheses and studies of the running droplets phenomenon. Key to
      repeatability is the observation and registration of an appropriate reference
      point upon which subsequent sublimation conditions are based. The reference point
      is established using reflection high-energy electron diffraction (RHEED), not the
      noncongruent temperature used in LEEM where temperature discrepancies up to 25
      degrees C against MBE is measured. Our approach removes instrumental barriers to
      the observation and control of this complex dynamical system and may extend the
      usefulness of many droplet-related processes. 

PMID- 25977658
TI  - Analysis of oxygen vacancy in Co-doped ZnO using the electron density
      distribution obtained using MEM.
AB  - Oxygen vacancy (VO) strongly affects the properties of oxides. In this study, we
      used X-ray diffraction (XRD) to study changes in the VO concentration as a
      function of the Co-doping level of ZnO. Rietveld refinement yielded a different
      result from that determined via X-ray photoelectron spectroscopy (XPS), but
      additional maximum entropy method (MEM) analysis led it to compensate for the
      difference. VO tended to gradually decrease with increased Co doping, and
      ferromagnetic behavior was not observed regardless of the Co-doping
      concentration. MEM analysis demonstrated that reliable information related to the
      defects in the ZnO-based system can be obtained using X-ray diffraction alone. 

PMID- 25977659
TI  - Sensory properties of hybrid composites based on poly(3,4-ethylenedioxythiophene)
      porous silicon-carbon nanotubes.
AB  - ABSTRACT: In this work, we have prepared film sensor elements based on a hybrid
      system poly(3,4-ethylenedioxythiophene)-porous silicon nanocrystals-carbon
      nanotubes on flexible polymer substrates. Our FTIR spectroscopy-based studies for
      the molecular structure of the materials obtained suggest some interaction of
      their components in the hybrid layer. The influence of adsorption of water
      molecules on the conductivity and capacitance of the hybrid composites has been
      investigated in the temperature range of 20 degrees C to 40 degrees C. We have
      detected essential changes in the electrical conductivity and capacitance which
      depend on the humidity of the surrounding atmosphere. For estimating the sensing
      properties of our composites, we have analyzed the sensing abilities of the
      hybrid systems and their dynamic characteristics. The hybrid composites as
      working materials for the sensors provide improved performance of the latter. In
      particular, the response time is reduced by 3 to 5 times. PACS: 73.63.-b,
      73.61.Ph, 82.35.Np, 81.05.Rm.

PMID- 25977660
TI  - Conductive-bridging random access memory: challenges and opportunity for 3D
      architecture.
AB  - The performances of conductive-bridging random access memory (CBRAM) have been
      reviewed for different switching materials such as chalcogenides, oxides, and
      bilayers in different structures. The structure consists of an inert electrode
      and one oxidized electrode of copper (Cu) or silver (Ag). The switching mechanism
      is the formation/dissolution of a metallic filament in the switching materials
      under external bias. However, the growth dynamics of the metallic filament in
      different switching materials are still debated. All CBRAM devices are switching
      under an operation current of 0.1 MUA to 1 mA, and an operation voltage of +/-2 V
      is also needed. The device can reach a low current of 5 pA; however, current
      compliance-dependent reliability is a challenging issue. Although a chalcogenide
      based material has opportunity to have better endurance as compared to an oxide
      based material, data retention and integration with the complementary metal-oxide
      semiconductor (CMOS) process are also issues. Devices with bilayer switching
      materials show better resistive switching characteristics as compared to those
      with a single switching layer, especially a program/erase endurance of >10(5)
      cycles with a high speed of few nanoseconds. Multi-level cell operation is
      possible, but the stability of the high resistance state is also an important
      reliability concern. These devices show a good data retention of >10(5) s at >85
      degrees C. However, more study is needed to achieve a 10-year guarantee of data
      retention for non-volatile memory application. The crossbar memory is benefited
      for high density with low power operation. Some CBRAM devices as a chip have been
      reported for proto-typical production. This review shows that operation current
      should be optimized for few microamperes with a maintaining speed of few
      nanoseconds, which will have challenges and also opportunities for three
      dimensional (3D) architecture. 

PMID- 25977661
TI  - Plasmonic lens focused longitudinal field excitation for tip-enhanced Raman
      spectroscopy.
AB  - A novel tip-enhanced Raman spectroscopy setup with longitudinal field excitation
      generated by a plasmonic lens is investigated. A symmetry-breaking structure
      plasmonic lens that is expected to realize a strong longitudinal electric field
      focus has been designed to generate suitable excitation for enhancement in a tip
      antenna. The focusing performance of the plasmonic lens is theoretically
      simulated by the finite-difference time-domain method and experimentally verified
      by the detection of optical near-field distribution. A plasmonic lens assisted
      tip-enhanced Raman spectroscopy setup has been constructed and used to
      investigate specimens of carbon nanotubes. Tip-enhanced Raman spectra with
      distinct excitation wavelengths show similar Raman shifts but different
      intensities. Experimental results presented in this paper demonstrate that the
      Raman signal is considerably enhanced. It indicates that the novel tip-enhanced
      Raman spectroscopy configuration is feasible and is a promising technique for tip
      enhanced Raman spectroscopy measurements and characterizations. 

PMID- 25977662
TI  - Hybrid Si nanocones/PEDOT:PSS solar cell.
AB  - Periodic silicon nanocones (SiNCs) with different periodicities are fabricated by
      dry etching of a Si substrate patterned using monolayer polystyrene (PS)
      nanospheres as a mask. Hybrid Si/ PEDOT: PSS solar cells based on the SiNCs are
      then fabricated and characterized in terms of their optical, electrical, and
      photovoltaic properties. The optical properties of the SiNCs are also
      investigated using theoretical simulation based on the finite element method. The
      SiNCs reveal excellent light trapping ability as compared to a planar Si
      substrate. It is found that the power conversion efficiency (PCE) of the hybrid
      cells decreases with increasing periodicity of the SiNCs. The highest PCE of 7.1%
      is achieved for the SiNC hybrid cell with a 400-nm periodicity, due to the strong
      light trapping near the peak of the solar spectrum and better current collection
      efficiency. PACS: 81.07.-b; 81.16.-c; 88.40.hj.

PMID- 25977663
TI  - Fabrication of high-quality graphene oxide nanoscrolls and application in
      supercapacitor.
AB  - We reported a simple and effective way of fabricating one-dimensional (1D)
      graphene oxide nanoscrolls (GONS) from graphene oxide (GO) sheets through shock
      cooling by liquid nitrogen. The corresponding mechanism of rolling was proposed.
      One possibility is the formation of ice crystals during the shock cooling process
      in liquid nitrogen to be the driving force. The other might be due to the uneven
      stress of the sheets inside or outside ice during the lyophilization. After
      reducing, graphene nanoscrolls (GNS) exhibited good structural stability, high
      specific surface area, and high specific capacitance. The capacitance properties
      were investigated by cyclic voltammetry, galvanostatic charge-discharge, and
      electrical impedance spectroscopy. A specific capacity of 156 F/g for the GNS at
      the current density of 1.0 A/g was obtained comparing with the specific capacity
      of 108 F/g for graphene sheets. Those results indicated that GNS-based rolling
      structure could be a kind of promising electrode material for supercapacitors and
      batteries. 

PMID- 25977664
TI  - Controllable synthesis porous Ag2CO3 nanorods for efficient photocatalysis.
AB  - The novel porous Ag2CO3 nanorods were facilely synthesized via a one-pot aqueous
      solution reaction at room temperature. The crystalline phase and size
      distribution of the nanorods were determined by X-ray diffraction (XRD) and
      scanning electron microscopy (SEM), respectively. In addition, the porous feature
      of nanorods was confirmed by transmission electron microscopy (TEM) and nitrogen
      adsorption-desorption. The morphology and size of the Ag2CO3 crystal can be
      regulated via the choice of dispersing agents and adding approaches of reactants.
      Photocatalytic results show that the porous Ag2CO3 nanorods exhibit excellent
      photodegradation of rhodamine B (RhB) under visible-light irradiation,
      particularly the photoactivity performance and stability can be further improved
      in the presence of sodium bicarbonate (NaHCO3). It is indicated that NaHCO3 can
      prevent effectively the photocorrosion and promote the probability of electron
      hole separation. 

PMID- 25977665
TI  - The energy transfer mechanism of a photoexcited and electroluminescent organic
      hybrid thin film of blue, green, and red laser dyes.
AB  - Though optically pumped lasing has been realized for years, electrically pumped
      lasing has not yet been achieved in organic semiconductor devices. In order to
      make a better understanding of the laser mechanisms of the organic materials, we
      prepared organic thin films consisting of three efficient laser dyes of a blue
      emitter, 4",4"'-N,N-diphenylamine-4,4'-diphenyl-1,1'-binaphthyl (BN), a green
      emitter, 1,4-bis[2-[4-[N,N-di(p-tolyl)amino] phenyl]vinyl]benzene (DSB), and a
      red emitter, 4-(dicyanomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidy-l-9
      enyl)-4H-pyran (DCJTB) with different doping concentrations for the first time to
      investigate the cascade energy transfer process. The energy transfer schemes in
      the co-doped thin films in photoluminescence and electroluminescence have been
      investigated. The results indicated that the DSB molecules acted as a bridge to
      deliver energy more effectively from the host (BN) to the guest (DCJTB).
      Meanwhile, the maximum current efficiency (C E) and power efficiency (P E) of the
      organic light-emitting devices (OLEDs) with the emitting layer of lower doping
      concentration were 13.5 cd/A and 14.1 lm/W, respectively. 

PMID- 25977667
TI  - Ability of dynamic holography in self-assembled hybrid nanostructured silica
      films for all-optical switching and multiplexing.
AB  - The sol-gel method has been employed in the fabrication of easily processable
      mesostructured films consisting of a nonionic surfactant and silica as the
      inorganic component. The ability of the occluded Pluronic P123 mesostructures to
      solubilize guest molecules made these films ideal host matrices for organic dyes
      and molecular assemblies, possessing substantial nonlinear susceptibilities.
      These films were explored for use as the photonic layer in all-optical time-to
      space converters and proved successful at increasing the optical response of the
      intercalated dyes to a point that would make these composite films applicable for
      use as the photonic layer. Recording of a dynamical grating in a single-pulse
      regime has been obtained. Since the dynamical grating exhibits the fast
      relaxation time (up to 10 ns), the nonlinear mechanism represents an electronic
      excitation of the photosensitive molecules. As far as the dye molecules are
      distributed in nanoporous silica, a model of 'gas of molecular dye' may be
      rightly used in order to consider nonlinear optical properties in the
      nanostructured hybrid films. We suppose that further improvement of the nonlinear
      optical nanomaterials may follow on the way to embed additional inclusions, which
      will not promote the heat accumulation in the host matrix and will lead to
      effective dissipation of the heat energy. PACS: 78.20.-e; 42.70 -a; 42.79.

PMID- 25977666
TI  - Facile synthesis and photocatalytic activity of bi-phase dispersible Cu-ZnO
      hybrid nanoparticles.
AB  - Bi-phase dispersible Cu-ZnO hybrid nanoparticles were synthesized by one-pot non
      aqueous nanoemulsion with the use of poly(ethylene glycol)-block-poly(propylene
      glycol)-block-poly(ethylene glycol) (PEO-PPO-PEO) as the surfactant. The
      transmission electron microscopy (TEM) and X-ray diffraction (XRD) show high
      crystallinity of the Cu-ZnO hybrid nanoparticles and an average particle size of
      ~19.4 nm. The ultraviolet-visible light absorbance spectrometry (UV-vis) and
      photoluminescence spectrophotometry (PL) demonstrate well dispersibility and
      excellent optical performance of Cu-ZnO hybrid nanoparticles both in organic and
      aqueous solvent. The X-ray photoelectron spectroscopy (XPS) confirms Cu(1+) and
      Cu(2+) in ZnO. The observation using Sudan red (III) as probe molecule reveals
      that the Cu-ZnO hybrid nanoparticles possess enhanced photocatalytic activity and
      stability which are promising for potential applications in photocatalysis. 

PMID- 25977668
TI  - Ag-Cu nanoalloyed film as a high-performance cathode electrocatalytic material
      for zinc-air battery.
AB  - A novel Ag50Cu50 film electrocatalyst for oxygen reduction reaction (ORR) was
      prepared by pulsed laser deposition (PLD) method. The electrocatalyst actually is
      Ag-Cu alloyed nanoparticles embedded in amorphous Cu film, based on transmission
      electron microscopy (TEM) characterization. The rotating disk electrode (RDE)
      measurements provide evidence that the ORR proceed via a four-electron pathway on
      the electrocatalysts in alkaline solution. And it is much more efficient than
      pure Ag catalyst. The catalytic layer has maximum power density of 67 mW cm(-2)
      and an acceptable cell voltage at 0.863 V when current densities increased up to
      100 mA cm(-2) in the Ag50Cu50-based primary zinc-air battery. The resulting
      rechargeable zinc-air battery exhibits low charge-discharge voltage polarization
      of 1.1 V at 20 mAcm(-2) and high durability over 100 cycles in natural air. 

PMID- 25977669
TI  - Thermally modulated biomolecule transport through nanoconfined channels.
AB  - In this work, a nanofluidic device containing both a feed cell and a permeation
      cell linked by nanopore arrays has been fabricated, which is employed to
      investigate thermally controlled biomolecular transporting properties through
      confined nanochannels. The ionic currents modulated by the translocations of goat
      antibody to human immunoglobulin G (IgG) or bovine serum albumin (BSA) are
      recorded and analyzed. The results suggest that the modulation effect decreases
      with the electrolyte concentration increasing, while the effects generated by IgG
      translocation are more significant than that generated by BSA translocation. More
      importantly, there is a maximum decreasing value in each modulated current curve
      with biomolecule concentration increasing for thermally induced intermolecular
      collision. Furthermore, the turning point for the maximum shifts to lower
      biomolecule concentrations with the system temperature rising (from 4 degrees C
      to 45 degrees C), and it is mainly determined by the temperature in the feed cell
      if the temperature difference exists in the two separated cells. These findings
      are expected to be valuable for the future design of novel sensing device based
      on nanopore and/or nanopore arrays. 

PMID- 25977670
TI  - Structure design and photocatalytic properties of one-dimensional SnO2-TiO2
      composites.
AB  - One-dimensional SnO2-TiO2 composites were prepared via emulsion electrospinning
      process. The obtained samples were characterized by a series of devices. The
      results showed that the porous core-shell SnO2-TiO2 photocatalyst exhibited
      enhanced photocatalytic activity on the degradation of methyl orange (MO). It
      should be ascribed to the novel structure, which could separate the electrons and
      holes effectively. 

PMID- 25977671
TI  - Erratum to: Plasmonic molecules via glass annealing in hydrogen.
AB  - [This corrects the article DOI: 10.1186/1556-276X-9-606.]. 

PMID- 25977672
TI  - Raman scattering study on Sb spray InAs/GaAs quantum dot nanostructure systems.
AB  - The effect of Sb spray time on the structure of InAs/GaAs quantum dot (QD)
      systems with Sb spray prior to the capping of a GaAs layer was determined by a
      Raman scattering study. The Raman spectra of the InAs/GaAs system show two phonon
      signal bands related to interface (IF) defects, located at the low-energy side of
      InAs QDs and GaAs cap layer main phonon peaks, respectively. The intensity ratio
      of the IF defect relative phonon signal to its corresponding main peak shows a
      significant decrease with the Sb spray time increasing from 0 to 15 s, but
      increases for spray times larger than 15 s. In addition, the InAs QD phonon peaks
      appear to be resolved with improved symmetry for 15 s of spray time. Finally, the
      GaAs transverse optical (TO) phonon peak is seen to vary with Sb spray time, both
      in terms of the intensity and the peak position, in a similar manner to the other
      results. Taken together, these results suggest the InAs/GaAs QDs with a 15-s Sb
      spray lead to a GaAs capping layer with less strain at the IF with the QDs and a
      lower density of crystalline defects. PACS: 81.05.Ea; 81.07.-b; 81.07.Ta.

PMID- 25977674
TI  - Reduced graphene oxide/carbon double-coated 3-D porous ZnO aggregates as high
      performance Li-ion anode materials.
AB  - The reduced graphene oxide (RGO)/carbon double-coated 3-D porous ZnO aggregates
      (RGO/C/ZnO) have been successfully synthesized as anode materials for Li-ion
      batteries with excellent cyclability and rate capability. The mesoporous ZnO
      aggregates prepared by a simple solvothermal method are sequentially modified
      through distinct carbon-based double coating. These novel architectures take
      unique advantages of mesopores acting as space to accommodate volume expansion
      during cycling, while the conformal carbon layer on each nanoparticle buffering
      volume changes, and conductive RGO sheets connect the aggregates to each other.
      Consequently, the RGO/C/ZnO exhibits superior electrochemical performance,
      including remarkably prolonged cycle life and excellent rate capability. Such
      improved performance of RGO/C/ZnO may be attributed to synergistic effects of
      both the 3-D porous nanostructures and RGO/C double coating. 

PMID- 25977673
TI  - BMP2 gene delivery to bone mesenchymal stem cell by chitosan-g-PEI nonviral
      vector.
AB  - Nanotechnology has made a significant impact on the development of nanomedicine.
      Nonviral vectors have been attracting more attention for the advantage of
      biosafety in gene delivery. Polyethylenimine (PEI)-conjugated chitosan (chitosan
      g-PEI) emerged as a promising nonviral vector and has been demonstrated in many
      tumor cells. However, there is a lack of study focused on the behavior of this
      vector in stem cells which hold great potential in regenerative medicine.
      Therefore, in this study, in vitro gene delivering effect of chitosan-g-PEI was
      investigated in bone marrow stem cells. pIRES2-ZsGreen1-hBMP2 dual expression
      plasmid containing both the ZsGreen1 GFP reporter gene and the BMP2 functional
      gene was constructed for monitoring the transgene expression level. Chitosan-g
      PEI-mediated gene transfer showed 17.2% of transfection efficiency and more than
      80% of cell viability in stem cells. These values were higher than that of PEI.
      The expression of the delivered BMP2 gene in stem cells enhanced the osteogenic
      differentiation. These results demonstrated that chitosan-g-PEI is capable of
      applying in delivering gene to stem cells and providing potential applications in
      stem cell-based gene therapy. 

PMID- 25977675
TI  - DNA-functionalized silicon nitride nanopores for sequence-specific recognition of
      DNA biosensor.
AB  - Nanopores have been proven to be novel and versatile single-molecule sensors for
      individual unlabeled biopolymer detection and characterization. In the present
      study, a relatively large silicon nitride (Si3N4) nanopore with a diameter of
      approximately 60 nm was fabricated successfully using a focused Ga ion beam
      (FIB). We demonstrated a simple ex situ silanization procedure to control the
      size and functionality of solid-state nanopores. The presented results show that
      by varying the silanization time, it is possible to adjust the efficiency of
      probe molecule attachment, thus shrinking the pore to the chosen size, while
      introducing selective sensing probes. The functionalization of nanopores was
      verified by analysis of field-emission scanning electron microscopy (FESEM),
      energy-dispersive X-ray spectroscopy (EDS), and electrical measurements. Based on
      this study, we envision that the functionalized silicon nitride nanopores with
      the DNA probe might provide a biosensing platform for the detection and
      discrimination of a short single-stranded DNA oligomer of unknown sequences in
      the future. 

PMID- 25977676
TI  - Can Tea Consumption be a Safe and Effective Therapy Against Diabetes Mellitus
      Induced Neurodegeneration?
AB  - Diabetes mellitus (DM) is a metabolic disease that is rapidly increasing and has
      become a major public health problem. Type 2 DM (T2DM) is the most common type,
      accounting for up to 90-95% of the new diagnosed DM cases. The brain is very
      susceptible to glucose fluctuations and hyperglycemia-induced oxidative stress
      (OS). It is well known that DM and the risk of developing neurodegenerative
      diseases are associated. Tea, Camellia sinensis L., is one of the most consumed
      beverages. It contains several phytochemicals, such as polyphenols,
      methylxanthines (mainly caffeine) and L-theanine that are often reported to be
      responsible for tea's health benefits, including in brain. Tea phytochemicals
      have been reported to be responsible for tea's significant antidiabetic and
      neuroprotective properties and antioxidant potential. Epidemiological studies
      have shown that regular consumption of tea has positive effects on DM-caused
      complications and protects the brain against oxidative damage, contributing to an
      improvement of the cognitive function. Among the several reported benefits of tea
      consumption, those related with neurodegenerative diseases are of great interest.
      Herein, we discuss the potential beneficial effects of tea consumption and tea
      phytochemicals on DM and how their action can counteract the severe brain damage
      induced by this disease. 

PMID- 25977677
TI  - An update of the classical and novel methods used for measuring fast
      neurotransmitters during normal and brain altered function.
AB  - To understand better the cerebral functions, several methods have been developed
      to study the brain activity, they could be related with morphological,
      electrophysiological, molecular and neurochemical techniques. Monitoring
      neurotransmitter concentration is a key role to know better how the brain works
      during normal or pathological conditions, as well as for studying the changes in
      neurotransmitter concentration with the use of several drugs that could affect or
      reestablish the normal brain activity. Immediate response of the brain to
      environmental conditions is related with the release of the fast acting
      neurotransmission by glutamate (Glu), gamma-aminobutyric acid (GABA) and
      acetylcholine (ACh) through the opening of ligand-operated ion channels.
      Neurotransmitter release is mainly determined by the classical microdialysis
      technique, this is generally coupled to high performance liquid chromatography
      (HPLC). Detection of neurotransmitters can be done by fluorescence, optical
      density, electrochemistry or other detection systems more sophisticated. Although
      the microdialysis method is the golden technique to monitor the brain
      neurotransmitters, it has a poor temporal resolution. Recently, with the use of
      biosensor the drawback of temporal resolution has been improved considerably,
      however other inconveniences have merged, such as stability, reproducibility and
      the lack of reliable biosensors mainly for GABA. The aim of this review is to
      show the important advances in the different ways to measure neurotransmitter
      concentrations; both with the use of classic techniques as well as with the novel
      methods and alternant approaches to improve the temporal resolution. 

PMID- 25977678
TI  - ON-OFF Interactions in the Retina: Role of Glycine and GABA.
AB  - In the vertebrate retina, visual signals are segregated into parallel ON and OFF
      pathways, which provide information for light increments and decrements. The
      segregation is first evident at the level of the ON and OFF bipolar cells and it
      apparently remains as signals propagate to higher brain visual centers. A
      fundamental question in visual neuroscience is how these two parallel pathways
      function: are they independent from each other or do they interact somehow? In
      the latter case, what kinds of mechanisms are involved and what are the
      consequences from this cross-talk? This review summarizes current knowledge about
      the types of interactions between the ON and OFF channels in nonmammalian and
      mammalian retina. Data concerning the ON-OFF interactions in distal retina
      revealed by recording of single bipolar cell activity and electroretinographic ON
      (b-wave) and OFF (d-wave) responses are presented. Special emphasis is put on the
      ON-OFF interactions in proximal retina and their dependence on the state of light
      adaptation in mammalian retina. The involvement of the GABAergic and glycinergic
      systems in the ON-OFF crosstalk is also discussed. 

PMID- 25977681
TI  - The many roles of statins in ischemic stroke.
AB  - Stroke is the third leading cause of human death. Endothelial dysfunction,
      thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play
      an important role in cerebral ischemic pathogenesis and represent a target for
      prevention and treatment. Statins have been found to improve endothelial
      function, modulate thrombogenesis, attenuate inflammatory and oxidative stress
      damage, and facilitate angiogenesis far beyond lowering cholesterol levels.
      Statins have also been proved to significantly decrease cardiovascular risk and
      to improve clinical outcome. Could statins be the new candidate agent for the
      prevention and therapy in ischemic stroke? In recent years, a vast expansion in
      the understanding of the pathophysiology of ischemic stroke and the pleiotropic
      effects of statins has occurred and clinical trials involving statins for the
      prevention and treatment of ischemic stroke have begun. These facts force us to
      revisit ischemic stroke and consider new strategies for prevention and treatment.
      Here, we survey the important developments in the non-lipid dependent pleiotropic
      effects and clinical effects of statins in ischemic stroke. 

PMID- 25977679
TI  - Antioxidants as a preventive treatment for epileptic process: a review of the
      current status.
AB  - Epilepsy is known as one of the most frequent neurological diseases,
      characterized by an enduring predisposition to generate epileptic seizures.
      Oxidative stress is believed to directly participate in pathways leading to
      neurodegeneration, which serves as the most important propagating factor, leading
      to the epileptic condition and cognitive decline. Moreover, there is also a
      growing body of evidence showing the disturbance of antioxidant system balance
      and consequently increased production of reactive species in patients with
      epilepsy. A meta-analysis, conducted in the present review confirms an
      association between epilepsy and increased lipid peroxidation. Furthermore, it
      was also shown that some of the antiepileptic drugs could potentially be
      responsible for additionally increased lipid peroxidation. Therefore, it is
      reasonable to propose that during the epileptic process neuroprotective treatment
      with antioxidants could lead to less sever structural damages, reduced
      epileptogenesis and milder cognitive deterioration. To evaluate this hypothesis
      studies investigating the neuroprotective therapeutic potential of various
      antioxidants in cells, animal seizure models and patients with epilepsy have been
      reviewed. Numerous beneficial effects of antioxidants on oxidative stress markers
      and in some cases also neuroprotective effects were observed in animal seizure
      models. However, despite these encouraging results, till now only a few
      antioxidants have been further applied to patients with epilepsy as an add-on
      therapy. Based on the several positive findings in animal models, a strong need
      for more carefully planned, randomized, double-blind, cross-over, placebo
      controlled clinical trials for the evaluation of antioxidants efficacy in
      patients with epilepsy is warranted. 

PMID- 25977680
TI  - Recent progress of imaging agents for Parkinson's disease.
AB  - Parkinson's disease (PD) is a common progressive, neurodegenerative brain disease
      that is promoted by mitochondrial dysfunction, oxidative stress, protein
      aggregation and proteasome dysfunction in the brain. Compared with computer
      tomography (CT) or magnetic resonance imaging (MRI), non-invasive nuclear
      radiopharmaceuticals have great significance for the early diagnosis of PD due to
      their high sensitivity and specificity in atypical and preclinical cases. Based
      on the development of coordination chemistry and chelator design, radionuclides
      may be delivered to lesions by attaching to PD-related transporters and
      receptors, such as dopamine, serotonin, and others. In this review, we
      comprehensively detailed the current achievements in radionuclide imaging in
      Parkinson's disease. 

PMID- 25977682
TI  - Automatic extraction of blood vessels in the retinal vascular tree using
      multiscale medialness.
AB  - We propose an algorithm for vessel extraction in retinal images. The first step
      consists of applying anisotropic diffusion filtering in the initial vessel
      network in order to restore disconnected vessel lines and eliminate noisy lines.
      In the second step, a multiscale line-tracking procedure allows detecting all
      vessels having similar dimensions at a chosen scale. Computing the individual
      image maps requires different steps. First, a number of points are preselected
      using the eigenvalues of the Hessian matrix. These points are expected to be near
      to a vessel axis. Then, for each preselected point, the response map is computed
      from gradient information of the image at the current scale. Finally, the
      multiscale image map is derived after combining the individual image maps at
      different scales (sizes). Two publicly available datasets have been used to test
      the performance of the suggested method. The main dataset is the STARE project's
      dataset and the second one is the DRIVE dataset. The experimental results,
      applied on the STARE dataset, show a maximum accuracy average of around 94.02%.
      Also, when performed on the DRIVE database, the maximum accuracy average reaches
      91.55%. 

PMID- 25977683
TI  - A low-noise, modular, and versatile analog front-end intended for processing in
      vitro neuronal signals detected by microelectrode arrays.
AB  - The collection of good quality extracellular neuronal spikes from neuronal
      cultures coupled to Microelectrode Arrays (MEAs) is a binding requirement to
      gather reliable data. Due to physical constraints, low power requirement, or the
      need of customizability, commercial recording platforms are not fully adequate
      for the development of experimental setups integrating MEA technology with other
      equipment needed to perform experiments under climate controlled conditions, like
      environmental chambers or cell culture incubators. To address this issue, we
      developed a custom MEA interfacing system featuring low noise, low power, and the
      capability to be readily integrated inside an incubator-like environment. Two
      stages, a preamplifier and a filter amplifier, were designed, implemented on
      printed circuit boards, and tested. The system is characterized by a low input
      referred noise (<1 MUV RMS), a high channel separation (>70 dB), and signal-to
      noise ratio values of neuronal recordings comparable to those obtained with the
      benchmark commercial MEA system. In addition, the system was successfully
      integrated with an environmental MEA chamber, without harming cell cultures
      during experiments and without being damaged by the high humidity level. The
      devised system is of practical value in the development of in vitro platforms to
      study temporally extended neuronal network dynamics by means of MEAs.

PMID- 25977684
TI  - Initialization by a novel clustering for wavelet neural network as time series
      predictor.
AB  - The architecture and parameter initialization of wavelet neural network are
      discussed and a novel initialization method is proposed. The new approach can be
      regarded as a dynamic clustering procedure which will derive the neuron number as
      well as the initial value of translation and dilation parameters according to the
      input patterns and the activating wavelets functions. Three simulation examples
      are given to examine the performance of our method as well as Zhang's heuristic
      initialization approach. The results show that the new approach not only can
      decide the WNN structure automatically, but also provides superior initial
      parameter values that make the optimization process more stable and quickly. 

PMID- 25977685
TI  - Feature Selection Applying Statistical and Neurofuzzy Methods to EEG-Based BCI.
AB  - This paper presents an investigation aimed at drastically reducing the processing
      burden required by motor imagery brain-computer interface (BCI) systems based on
      electroencephalography (EEG). In this research, the focus has moved from the
      channel to the feature paradigm, and a 96% reduction of the number of features
      required in the process has been achieved maintaining and even improving the
      classification success rate. This way, it is possible to build cheaper, quicker,
      and more portable BCI systems. The data set used was provided within the
      framework of BCI Competition III, which allows it to compare the presented
      results with the classification accuracy achieved in the contest. Furthermore, a
      new three-step methodology has been developed which includes a feature
      discriminant character calculation stage; a score, order, and selection phase;
      and a final feature selection step. For the first stage, both statistics method
      and fuzzy criteria are used. The fuzzy criteria are based on the S-dFasArt
      classification algorithm which has shown excellent performance in previous papers
      undertaking the BCI multiclass motor imagery problem. The score, order, and
      selection stage is used to sort the features according to their discriminant
      nature. Finally, both order selection and Group Method Data Handling (GMDH)
      approaches are used to choose the most discriminant ones. 

PMID- 25977686
TI  - Comment on "metabolic changes and serum ghrelin level in patients with
      psoriasis".

PMID- 25977687
TI  - D-lactic acidosis: an underrecognized complication of short bowel syndrome.
AB  - D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs
      primarily in individuals who have a history of short bowel syndrome. The
      unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic
      acid among other organic acids. The acidic pH generated as a result of D-lactate
      production further propagates production of D-lactic acid, hence giving rise to a
      vicious cycle. D-lactic acid accumulation in the blood can cause neurologic
      symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a
      combination of clinical and laboratory data including special assays for D
      lactate. Treatment includes correcting the acidosis and decreasing substrate for
      D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to
      clear colonic flora. Although newer techniques for diagnosis and treatment are
      being developed, clinical diagnosis still holds paramount importance, as there
      can be many confounders in the diagnosis as will be discussed subsequently. 

PMID- 25977688
TI  - Feasibility and Safety of Overtubes for PEG-Tube Placement in Patients with Head
      and Neck Cancer.
AB  - Background. Percutaneous endoscopic gastrostomy (PEG) placement using the "pull"
      technique is commonly utilized for providing nutritional support in head and neck
      cancer (HNC) patients, but it may be complicated by peristomal metastasis in up
      to 3% of patients. Overtube-assisted PEG placement might reduce this risk.
      However, this technique has not been systemically studied for this purpose to
      date. Methods. Retrospective analysis of consecutive patients with HNC who
      underwent overtube-assisted PEG placement at Westmead Hospital, Australia,
      between June 2011 and December 2013. Data were extracted from patients' endoscopy
      reports and case notes. We present our technique for PEG insertion and discuss
      the feasibility and safety of this method. Results. In all 53 patients studied,
      the PEG tubes were successfully placed using 25 cm long flexible overtubes, in
      89% prophylactically (before commencing curative chemoradiotherapy), and in 11%
      reactively (for treatment of tumor related dysphagia or weight loss). During a
      median follow-up period of 16 months, 3 (5.7%) patients developed peristomal
      infection and 3 others developed self-limiting peristomal pain. There were no
      cases of overtube-related adverse events or overt cutaneous metastases observed.
      Conclusions. Overtube-assisted PEG placement in patients with HNC is a feasible,
      simple, and safe technique and might be effective for preventing cutaneous
      metastasis. 

PMID- 25977689
TI  - Expression of Helicobacter pylori hspA Gene in Lactococcus lactis NICE System and
      Experimental Study on Its Immunoreactivity.
AB  - Aim. The aim of this study was to develop an oral Lactococcus lactis (L. lactis)
      vaccine against Helicobacter pylori (H. pylori). Methods. After L. lactis
      NZ3900/pNZ8110-hspA was constructed, growth curves were plotted to study whether
      the growth of recombinant L. lactis was affected after hspA was cloned into L.
      lactis and whether the growth of empty bacteria, empty plasmid bacteria, and
      recombinant L. lactis was affected by different concentrations of Nisin; SDS-PAGE
      and Western blot were adopted, respectively, to detect the HspA expressed by
      recombinant L. lactis and its immunoreactivity. Results. There was no effect
      observed from the growth curve after exogenous gene hspA was cloned into L.
      lactis NZ3900; different concentrations of Nisin did not affect the growth of
      NZ3900 and NZ3900/pNZ8110, while different concentrations of Nisin inhibited the
      growth of NZ3900/pNZ8110-hspA except 10 ng/mL Nisin. No HspA strip was observed
      from SDS-PAGE. Western blot analysis showed that HspA expressed by recombinant
      bacteria had favorable immunoreactivity. Conclusion. The growth of recombinant L.
      lactis was suppressed even though a small amount of HspA had been induced to
      express. Therefore recombinant L. lactis only express HspA which was not suitable
      to be oral vaccine against Helicobacter pylori. 

PMID- 25977690
TI  - Correlation between B-Type Natriuretic Peptide and Functional/Cognitive
      Parameters in Discharged Congestive Heart Failure Patients.
AB  - The determination of B-type natriuretic peptides (BNP) may have a role in the
      diagnosis of heart failure (HF) or guiding HF therapy. This study investigated
      the role of BNP determination in a cohort of elderly patients admitted to
      hospital with acute decompensated HF and its correlation with main demographic,
      clinical, and instrumental data and evaluated possible association with major
      outcome such as mortality or readmission after a 6-month period of follow-up.
      Methods. From October 2011 to May 2014 consecutive patients admitted to our unit
      with symptoms of acute HF or worsening of chronic HF entered the study collecting
      functional, echocardiographic, and hydration parameters. Correlation between BNP
      and main parameters was analysed, as well as the mortality/6-month readmission
      rate. Results. In 951 patients (mean age 71 ys; 37% females) a positive
      correlation was obtained between BNP and age, creatinine levels, NYHA class at
      admission and discharge, and levels of hydration; an inverse, negative
      correlation between BNP and sodium levels, LVEF, distance performed at 6MWT at
      admission and at discharge, and scores at MMSE at admission and discharge
      emerged. BNP levels at admission and at discharge were furthermore clearly
      associated with mortality at 6 months (Chi-square 704.38, p = 0.03) and hospital
      readmission (Chi-square 741.57, p < 0.01). Conclusion. In an elderly HF
      population, BNP is related not only with clinical, laboratory, and instrumental
      data but also with multidimensional scales evaluating global status; higher BNP
      levels are linked with a worse prognosis in terms of mortality and 6-month
      readmission. 

PMID- 25977691
TI  - Association of ABO Blood Group Phenotype and Allele Frequency with Chikungunya
      Fever.
AB  - Background. The objective of this study was to investigate the association of the
      ABO blood group phenotype and allele frequency with CHIK fever. Methods. A rural
      community survey in Southern Thailand was conducted in August and September 2010.
      A total of 506 villagers were enrolled. Cases were defined as individuals having
      anti-CHIK IgG by hemagglutination >=1 : 10. Results. There were 314 cases (62.1%)
      with CHIK seropositivity. Females were less likely to have positive anti-CHIK IgG
      with odds ratio (OR) (95% CI) of 0.63 (0.43, 0.93). All samples tested were Rh
      positive. Distribution of CHIK seropositivity versus seronegativity (P value) in
      A, B, AB, and O blood groups was 80 versus 46 (0.003), 80 versus 48 (0.005), 24
      versus 20 (0.55), and 130 versus 78 (<0.001), respectively. However, chi-square
      test between ABO and CHIK infection showed no statistical significance (P =
      0.76). Comparison of the ABO blood group allele frequency between CHIK
      seropositivity and seronegativity was not statistically significant. Conclusion.
      This finding demonstrated no association of the ABO blood group phenotypes and
      allele frequencies with CHIK infection. 

PMID- 25977692
TI  - Rhabdomyosarcoma of the upper lip in an adult patient.
AB  - Rhabdomyosarcoma (RMS) is a high-grade, malignant mesenchymal neoplasm. These
      tumors represent the most common soft tissue sarcomas of children and
      adolescents. RMS is uncommon on the lip and it is rarely seen in adults. Here, we
      report a rare case of primary RMS, embryonal type, occurring on the upper lip in
      a 27-year-old female. 

PMID- 25977693
TI  - Dynamic network-based relevance score reveals essential proteins and functional
      modules in directed differentiation.
AB  - The induction of stem cells toward a desired differentiation direction is
      required for the advancement of stem cell-based therapies. Despite successful
      demonstrations of the control of differentiation direction, the effective use of
      stem cell-based therapies suffers from a lack of systematic knowledge regarding
      the mechanisms underlying directed differentiation. Using dynamic modeling and
      the temporal microarray data of three differentiation stages, three dynamic
      protein-protein interaction networks were constructed. The interaction difference
      networks derived from the constructed networks systematically delineated the
      evolution of interaction variations and the underlying mechanisms. A proposed
      relevance score identified the essential components in the directed
      differentiation. Inspection of well-known proteins and functional modules in the
      directed differentiation showed the plausibility of the proposed relevance score,
      with the higher scores of several proteins and function modules indicating their
      essential roles in the directed differentiation. During the differentiation
      process, the proteins and functional modules with higher relevance scores also
      became more specific to the neuronal identity. Ultimately, the essential
      components revealed by the relevance scores may play a role in controlling the
      direction of differentiation. In addition, these components may serve as a
      starting point for understanding the systematic mechanisms of directed
      differentiation and for increasing the efficiency of stem cell-based therapies. 

PMID- 25977694
TI  - Economic burden of hepatitis B virus-related diseases: evidence from iran.
AB  - BACKGROUND: Hepatitis B infection is still the main cause of chronic liver
      disease in Iran, which is associated with significant economic and social costs.
      OBJECTIVES: This study aimed to estimate the financial burden caused by CHB
      infection and its complications in Iran. PATIENTS AND METHODS: Prevalence-based
      and bottom-up approaches were used to collect the data. Data on direct medical
      costs were extracted from outpatient medical records in a referral
      gastroenterology and hepatology research center, inpatient medical records in
      several major hospitals in Tehran and Shiraz in 2013, and the self-reports of
      specialists. Data on direct non-medical and indirect costs were collected based
      on the patients' self-reports through face-to-face interviews performed in the
      mentioned centers. To calculate the indirect costs, friction cost approach was
      used. To calculate the total cost-of-illness in Iran, the total cost per patient
      at each stage of the disease was estimated and multiplied by the total number of
      patients. RESULTS: The total annual cost for the activate population of CHB
      patients and for those receiving treatment at various disease stages were
      respectively 450 million and 226 million dollars, with 64% and 70% of which
      allocated to direct costs respectively, and 36% and 30% to indirect costs
      respectively. The total direct costs alone for each group were respectively 1.17%
      and 0.6% of the total health expenditure. Furthermore, the cost spent on drugs
      encompasses the largest proportion of the direct medical cost for all stages of
      the disease. CONCLUSIONS: According to the perspectives of payers, patients, and
      community, CHB infection can be considered as one of the diseases with a
      substantial economic burden; the disease, specifically in extreme cases, can be
      too expensive and costly for patients. Therefore, patients should be protected
      against more severe stages of the disease through proper treatment and early
      diagnosis.

PMID- 25977695
TI  - The factors affecting bone density in cirrhosis.
AB  - BACKGROUND: Bone loss is common in cirrhosis. However, the prevalence of
      osteopenia and osteoporosis has been heterogeneous in different reports.
      Reduction in bone formation with or without increase in bone resorption appears
      to be responsible for bone loss in these patients. OBJECTIVES: We aimed to
      investigate bone loss in patients with cirrhosis at different anatomical sites
      and key factors that might affect it. PATIENTS AND METHODS: In this cross
      sectional study, 97 patients with cirrhosis who were referred to Razi Hospital,
      Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using
      biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was
      done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy
      X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts,
      the United States). Statistical analysis was performed using SPSS 18. A P value <
      0.05 was considered statistically significant. RESULTS: A total of 97 patients
      with cirrhosis (55.7% male) and the mean age of 51 +/- 13 years and median body
      mass index (BMI) of 22.7 kg/m(2) were recruited over a two-year period.
      Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%),
      cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in
      16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal
      in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and
      calculated glomerular filtration rate (GFRc) had moderate positive and Child
      score had moderate negative significant correlation with T score in both
      anatomical sites. There was no significant association between abnormal DEXA and
      the causes of cirrhosis. The univariate analysis showed that the risk of abnormal
      results in DEXA was significantly higher in those with low BMI, current smoking,
      higher Child score, and low GFRc; however, in multivariate analysis, the abnormal
      results were more frequent in those with lower vitamin D, higher Child score, and
      less GFRc. CONCLUSIONS: Abnormal DEXA was highly prevalent among patients with
      cirrhosis. The risk of this finding was increased by lower vitamin D levels,
      advanced disease, and impaired renal function.

PMID- 25977696
TI  - Biosignals analysis for kidney function effect analysis of fennel aromatherapy.
AB  - Human effort in order to enjoy a healthy life is diverse. IT technology to these
      analyzes, the results of development efforts, it has been applied. Therefore, I
      use the care and maintenance diagnostic health management and prevention than
      treatment. In particular, the aromatherapy treatment easy to use without the side
      effects there is no irritation, are widely used in modern society. In this paper,
      we measured the aroma effect by applying a biosignal analysis techniques; an
      experiment was performed to analyze. In particular, we design methods and
      processes of research based on the theory aroma that affect renal function.
      Therefore, in this paper, measuring the biosignals and after fennel aromatherapy
      treatment prior to the enforcement of the mutual comparison, through the
      analysis, studies were carried out to analyze the effect of fennel aromatherapy
      therapy on kidney function. 

PMID- 25977697
TI  - Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and
      HepG2 Cells.
AB  - The present study was conducted to investigate the effect of Sagunja-tang on the
      lipid related disease in a rat model of menopausal hyperlipidemia and lipid
      accumulation in methyl-beta-cyclodextrin-induced HepG2 cells. In in vivo study
      using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and
      perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media
      thickness, and nonalcoholic steatohepatitis score, when compared to menopausal
      hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased
      the lipid accumulation, total cholesterol levels, and low-density/very-low
      density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-beta
      cyclodextrin-induced decrease in the protein levels of critical molecule involved
      in cholesterol synthesis, sterol regulatory element binding protein-2, and low
      density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3
      methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of
      AMP-activated protein kinase was stimulated by Sagunja-tang. These results
      suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation
      through regulation of cholesterol synthesis and AMPK activity in vitro. These
      observations support the idea that Sagunja-tang is bioavailable both in vivo and
      in vitro and could be developed as a preventive and therapeutic agent of
      hyperlipidemia in postmenopausal females. 

PMID- 25977698
TI  - Chinese medicine bu xu hua yu recipe for the regulation of treg/th17 ratio
      imbalance in autoimmune hepatitis.
AB  - Objectives. The aim of this study is researching the role of the Regulatory T
      cell (Treg)/T helper cell-17 (Th17) cell ratio imbalance in the pathogenesis of
      autoimmune hepatitis (AIH) and the use of the "Bu Xu Hua Yu" recipe in the
      treatment of AIH. Materials and Methods. Sixty adult male C57/BL6 mice were
      divided into six different groups. alpha-Galcer was injected abdominally for
      production of the animal models. Liver function tests, histological examinations,
      liver tissue Regulatory T cell, and T helper cell-17 levels tests were carried
      out. TGF-beta1, IL-10, IL-17, and expression of mRNA and protein levels of Foxp3
      and ROR-gammat were also assessed. Results. Bu Xu Hua Yu method increased the
      levels of Regulatory T cell, IL-10, and the expression of Foxp3 (P < 0.05) in
      mice liver tissues. Furthermore, there were decreases in the levels of T helper
      cell-17, IL-17, and expression of RORgammat mRNA and protein (P < 0.05). The
      ratio of Treg/Th17 was increased (P < 0.05). Conclusion. Mice with AIH have a
      Treg/Th17 ratio imbalance. Bu Xu Hua Yu method was able to restore the cellular
      balance of Treg/Th17 through the regulation of the expression of RORgammat and
      Foxp3 and can play an important role in the treatment of AIH. 

PMID- 25977699
TI  - Methanolic Extract of Ficus carica Linn. Leaves Exerts Antiangiogenesis Effects
      Based on the Rat Air Pouch Model of Inflammation.
AB  - The antiangiogenesis effect of Ficus carica leaves extract in an air pouch model
      of inflammation was investigated in rat. Inflammation was induced by injection of
      carrageenan into pouches. After antioxidant capacity and total phenolic content
      (TPC) investigations, the extract was administered at 5, 25, and 50 mg/pouch, and
      then the volume of exudates, the cell number, TNFalpha, PGE2, and VEGF levels
      were measured. Angiogenesis of granulation tissues was determined by measuring
      hemoglobin content. Based on the DPPH assay, the extract had significant
      antioxidant activity with TPC of 11.70 mg GAE/100 g dry sample. In addition,
      leukocyte accumulation and volume of exudate were significantly inhibited by the
      extract. Moreover, it significantly decreased the production of TNFalpha, PGE2,
      and VEGF, while angiogenesis was significantly inhibited by all administered
      doses. Interestingly, attenuation of angiogenesis and inflammatory parameters
      (except leukocyte accumulation) by the extract was similar to that shown by
      diclofenac. The extract has anti-inflammatory effects and ameliorated cell influx
      and exudation to the site of the inflammatory response which may be related to
      the local inhibition of TNFalpha, PGE2, and VEGF levels as similarly shown by
      diclofenac. The antiangiogenesis and anti-VEGF effects of Ficus carica may be
      correlated with its significant antioxidant potentials. 

PMID- 25977700
TI  - Transcriptional Regulation of CYP3A4/2B6/2C9 Mediated via Nuclear Receptor PXR by
      Helicid and Its Metabolites.
AB  - Objective. This study aims at establishing and validating an in vitro system to
      screen drug inducers of CYPs mediated via hPXR, as well as studying
      transcriptional regulation of CYPs mediated via hPXR by helicid and its two
      metabolites. Methods. Cloning the nuclear receptor hPXR and the promoters of
      CYP3A4, CYP2B6, CYP2C9, and inserting the trans-element to the upstream of
      firefly luciferase reporter gene of the pGL4.17 vectors, then cotransfecting the
      report vectors and hPXR expression plasmid to HepG2 cell line. After 24 hours,
      the transfected cells were treated with helicid (0.004, 0.04, and 0.4 MUmol/L)
      and its metabolite I and metabolite II (0.0004, 0.004, and 0.04 MUmol/L) for 48
      h, while rifampin (10 MUmol/L) was included as the positive control and 0.1% DMSO
      as the negative control group. Cells were lysized and luciferase activity was
      determined using a dual luciferase reporter assay kit. Results. Helicid and its
      metabolites did not significantly increase promoter activities of CYP3A4, CYP2B6,
      and CYP2C9 in HepG2 cells transfected with PXR expression plasmid (P > 0.05).
      Conclusion. PXR-expressed CYP3A4, CYP2B6, and CYP2C9 dual luciferase reporter
      gene platforms were successfully established, and helicid and its metabolites I,
      II do not significantly induce the transcription of CYP3A4, CYP2B6, and CYP2C9. 

PMID- 25977701
TI  - Metabolomics profiling to investigate the pharmacologic mechanisms of berberine
      for the treatment of high-fat diet-induced nonalcoholic steatohepatitis.
AB  - Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH),
      which has been addressed in many studies. In this study, we investigated the
      molecular pharmacology mechanisms of berberine using metabolomic techniques.
      Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in
      each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH
      model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling
      procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with
      histopathology and biochemical analyses were adopted to explore the mechanisms of
      berberine on the protective effects against NASH. Key Findings. (i) According to
      conventional test results, berberine treatment plays a fighting role in HFD
      induced NASH due to its beneficial effects against insulin resistance,
      inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques,
      metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC),
      lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13
      HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could
      provide potential metabolic biomarkers to address the pharmacological mechanisms
      of berberine. Conclusions. The parts of molecular pharmacological mechanisms of
      berberine for NASH treatment are related to the regulation of metabolic
      disruption involving phospholipid and unsaturated fatty acids in rats with NASH. 

PMID- 25977702
TI  - Linking habitat suitability to demography in a pond-breeding amphibian.
AB  - INTRODUCTION: Elucidating the relationship between habitat characteristics and
      population parameters is critical for effective conservation. Habitat suitability
      index (HSI) models are often used in wildlife management and conservation
      practice assuming that they predict species occurrence, abundance and demography.
      However, the relationship between vital rates such as survival and reproduction
      and habitat suitability has rarely been evaluated. In this study, we used pond
      occupancy and mark-recapture data to test whether HSI predicts occupancy,
      reproduction and survival probabilities. Our model species is the great crested
      newt (Triturus cristatus), a pond-breeding amphibian protected under the European
      Habitats Directive. RESULTS: Our results show a positive relationship between the
      HSI and reproduction probability, whereas pond occupancy and survival
      probabilities were not related to HSI. Mortality was found to be higher during
      breeding seasons when newts are in ponds than during terrestrial phases of adult
      newts. CONCLUSION: Habitat suitability models are increasingly applied to
      wildlife management and conservation practice. We found that the HSI model
      predicted reproduction probability, rather than occurrence or survival. If HSI
      models indicate breeding populations rather than mere species occurrences, they
      may be used to identify habitats of higher priority for conservation. Future HSI
      models might be improved through modelling breeding populations vs. non-breeding
      populations rather than presence/absence data. However, according to our results
      the most suitable habitat is not necessarily the habitat where demographic
      performance is best. We recommend that conservation practitioners should use HSI
      models cautiously because there may be no direct link between habitat
      suitability, demography and consequently, population viability.

PMID- 25977703
TI  - The legislative backgrounds of workplace health promotion in three European
      countries: a comparative analysis.
AB  - BACKGROUND: This article investigates the legal database and theoretical basis of
      workplace health promotion (WHP) in three European countries: Finland, Latvia and
      Lithuania, and aims to find insights into effective WHP implementation. METHODS:
      In November 2013, a stakeholders' survey was carried out. The questionnaire
      included questions about legal documents and non-legislative measures relevant to
      WHP, institutions and other bodies/organizations working in the field, WHP
      conception/definition, and implementation of WHP activities according to the
      enterprises' size. RESULTS: Only Finland has adopted a specific law on
      occupational health care (separate from occupational safety). ILO conventions No.
      161 (Occupational Health Services Convention) and No. 187 (Promotional Framework
      for Occupational Safety and Health Convention) are ratified only in Finland. In
      Finland, the Ministry of Social Affairs and Health acts as one ministry, while
      two Baltic countries have two separate ministries (one for health and another for
      social affairs). None of the countries has legally approved a definition of WHP.
      Latvia and Lithuania tend to separate WHP from other activities, whereas Finland
      integrates WHP into other occupational health and safety elements. CONCLUSIONS:
      Finland has a more extensive legislative and organizational background to WHP
      than Latvia and Lithuania. In defining WHP, all the countries refer to the
      Luxembourg Declaration on Workplace Health Promotion in the European Union.
      Finland's practice of integrating WHP into other occupational health and safety
      elements is important.

PMID- 25977704
TI  - Computer-aided lung nodule recognition by SVM classifier based on combination of
      random undersampling and SMOTE.
AB  - In lung cancer computer-aided detection/diagnosis (CAD) systems, classification
      of regions of interest (ROI) is often used to detect/diagnose lung nodule
      accurately. However, problems of unbalanced datasets often have detrimental
      effects on the performance of classification. In this paper, both minority and
      majority classes are resampled to increase the generalization ability. We propose
      a novel SVM classifier combined with random undersampling (RU) and SMOTE for lung
      nodule recognition. The combinations of the two resampling methods not only
      achieve a balanced training samples but also remove noise and duplicate
      information in the training sample and retain useful information to improve the
      effective data utilization, hence improving performance of SVM algorithm for
      pulmonary nodules classification under the unbalanced data. Eight features
      including 2D and 3D features are extracted for training and classification.
      Experimental results show that for different sizes of training datasets our RU
      SMOTE-SVM classifier gets the highest classification accuracy among the four
      kinds of classifiers, and the average classification accuracy is more than
      92.94%. 

PMID- 25977705
TI  - Exploring sampling in the detection of multicategory EEG signals.
AB  - The paper presents a structure based on samplings and machine leaning techniques
      for the detection of multicategory EEG signals where random sampling (RS) and
      optimal allocation sampling (OS) are explored. In the proposed framework, before
      using the RS and OS scheme, the entire EEG signals of each class are partitioned
      into several groups based on a particular time period. The RS and OS schemes are
      used in order to have representative observations from each group of each
      category of EEG data. Then all of the selected samples by the RS from the groups
      of each category are combined in a one set named RS set. In the similar way, for
      the OS scheme, an OS set is obtained. Then eleven statistical features are
      extracted from the RS and OS set, separately. Finally this study employs three
      well-known classifiers: k-nearest neighbor (k-NN), multinomial logistic
      regression with a ridge estimator (MLR), and support vector machine (SVM) to
      evaluate the performance for the RS and OS feature set. The experimental outcomes
      demonstrate that the RS scheme well represents the EEG signals and the k-NN with
      the RS is the optimum choice for detection of multicategory EEG signals. 

PMID- 25977706
TI  - MRI brain images healthy and pathological tissues classification with the aid of
      improved particle swarm optimization and neural network.
AB  - The advantages of magnetic resonance imaging (MRI) over other diagnostic imaging
      modalities are its higher spatial resolution and its better discrimination of
      soft tissue. In the previous tissues classification method, the healthy and
      pathological tissues are classified from the MRI brain images using HGANN. But
      the method lacks sensitivity and accuracy measures. The classification method is
      inadequate in its performance in terms of these two parameters. So, to avoid
      these drawbacks, a new classification method is proposed in this paper. Here, new
      tissues classification method is proposed with improved particle swarm
      optimization (IPSO) technique to classify the healthy and pathological tissues
      from the given MRI images. Our proposed classification method includes the same
      four stages, namely, tissue segmentation, feature extraction, heuristic feature
      selection, and tissue classification. The method is implemented and the results
      are analyzed in terms of various statistical performance measures. The results
      show the effectiveness of the proposed classification method in classifying the
      tissues and the achieved improvement in sensitivity and accuracy measures.
      Furthermore, the performance of the proposed technique is evaluated by comparing
      it with the other segmentation methods. 

PMID- 25977707
TI  - Concordant and discordant DNA methylation signatures of aging in human blood and
      brain.
AB  - BACKGROUND: DNA methylation is an epigenetic mark that balances plasticity with
      stability. While DNA methylation exhibits tissue specificity, it can also vary
      with age and potentially environmental exposures. In studies of DNA methylation,
      samples from specific tissues, especially brain, are frequently limited and so
      surrogate tissues are often used. As yet, we do not fully understand how DNA
      methylation profiles of these surrogate tissues relate to the profiles of the
      central tissue of interest. RESULTS: We have adapted principal component analysis
      to analyze data from the Illumina 450K Human Methylation array using a set of 17
      individuals with 3 brain regions and whole blood. All of the top five principal
      components in our analysis were associated with a variable of interest: principal
      component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were
      representative of tissue composition within brain and blood, respectively, and
      PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in
      both brain and blood). We validated our age-related PCs in four independent
      sample sets, including additional brain and blood samples and liver and buccal
      cells. Gene ontology analysis of all five PCs showed enrichment for processes
      that inform on the functions of each PC. CONCLUSIONS: Principal component
      analysis (PCA) allows simultaneous and independent analysis of tissue composition
      and other phenotypes of interest. We discovered an epigenetic signature of age
      that is not associated with cell type composition and required no correction for
      cellular heterogeneity.

PMID- 25977708
TI  - Protective socks for people with diabetes: a systematic review and narrative
      analysis.
AB  - Padded socks to protect the at-risk diabetic foot have been available for a
      number of years. However, the evidence base to support their use is not well
      known. We aimed to undertake a systematic review of padded socks for people with
      diabetes. Additionally, a narrative analysis of knitted stitch structures, yarn
      and fibres used together with the proposed benefits fibre properties may add to
      the sock. Assessment of the methodological quality was undertaken using a quality
      tool to assess non-randomised trials. From the 81 articles identified only seven
      met the inclusion criteria. The evidence to support to use of padded socks is
      limited. There is a suggestion these simple-to-use interventions could be of
      value, particularly in terms of plantar pressure reduction. However, the range of
      methods used and limited methodological quality limits direct comparison between
      studies. The socks were generally of a sophisticated design with complex use of
      knit patterns and yarn content. This systematic review provides limited support
      for the use of padded socks in the diabetic population to protect vulnerable
      feet. More high quality studies are needed; including qualitative components of
      sock wear and sock design, prospective randomized controlled trials and analysis
      of the cost-effectiveness of protective socks as a non-surgical intervention. 

PMID- 25977709
TI  - Matsuda-Heck reaction with arenediazonium tosylates in water.
AB  - An environmentally friendly Matsuda-Heck reaction with arenediazonium tosylates
      has been developed for the first time. A range of alkenes was arylated in good to
      quantitative yields in water. The reaction is significantly accelerated when
      carried out under microwave heating. The arylation of haloalkylacrylates with
      diazonium salts has been implemented for the first time. 

PMID- 25977710
TI  - Attempts to prepare an all-carbon indigoid system.
AB  - First attempts are described to prepare a precursor for an all-carbon analog of
      indigo, the tetracyclic triene 4. Starting from indan-2-one (9) the alpha
      methylene ketone 13 was prepared. Upon subjecting this compound to a McMurry
      coupling reaction, it dimerized to the bis-indene derivative 17, rather than
      providing the tetramethyl derivative of 4, the hydrocarbon 14. In a second
      approach, indan-1-one (18) was dimerized to the conjugated enedione 21 through
      the bis-1-indene dimer 19. All attempts to methylenate 21 failed, however. When
      19 was treated with the Tebbe reagent, the dimer 23 was produced, presumably
      through a Cope reaction of the intermediately generated isomer 22. The bis-indene
      derivative 23 can be alkylated with 1,2-dibromoethane to produce a 1:1 mixture of
      the spiro compounds 24 and 25. Although 9 could be reductively dimerized to 30,
      the conversion of this olefin to 14 failed. 

PMID- 25977711
TI  - Synthesis and chemosensing properties of cinnoline-containing poly(arylene
      ethynylene)s.
AB  - Novel poly(arylene ethynylene)s comprising a cinnoline core were prepared in high
      yields via a three-step methodology. A Richter-type cyclization of 2-ethynyl- and
      2-(buta-1,3-diynyl)aryltriazenes was used for cinnoline ring formation, followed
      by a Sonogashira coupling for the introduction of trimethylsilylethynyl moieties
      and a sila-Sonogashira coupling as the polycondensation technique. The
      fluorescence of the cinnoline-containing polymers in THF was highly sensitive to
      quenching by Pd(2+) ions. 

PMID- 25977712
TI  - The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5
      aminotetrazole as a way to novel azaheterocycles.
AB  - The interaction of 2-ethoxymethylidene-3-oxo esters and their analogues with 5
      aminotetrazole is an efficient synthetic approach to novel azaheterocycles. 2
      Ethoxymethylidene-3-oxo esters bearing alkyl substituents react with 5
      aminotetrazole to form ethyl 2-azido-4-alkylpyrimidine-5-carboxylates which are
      capable of subsequent nucleophilic substitution. The use of diethyl 2
      ethoxymethylidenemalonate in this reaction resulted in ethyl 7
      hydroxytetrazolo[1,5-a]pyrimidine-6-carboxylate, while ethyl 2
      ethoxymethylidenecyanoacetate yielded 5-[2,6-diamino-3,5
      bis(ethoxycarbonyl)pyridinium-1-yl]tetrazol-1-ide through an alternative pathway.
      Ethyl 2-benzoyl-3-ethoxyprop-2-enoate reacted with 5-aminotetrazole by two
      reaction routes to form ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-2-enoate
      and ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7
      dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate. 

PMID- 25977713
TI  - Electrochemical oxidation of cholesterol.
AB  - Indirect cholesterol electrochemical oxidation in the presence of various
      mediators leads to electrophilic addition to the double bond, oxidation at the
      allylic position, oxidation of the hydroxy group, or functionalization of the
      side chain. Recent studies have proven that direct electrochemical oxidation of
      cholesterol is also possible and affords different products depending on the
      reaction conditions. 

PMID- 25977714
TI  - Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF.
AB  - This review aims to give an overview of the current status of our research on the
      synthesis of pi-electron donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF,
      ET) analogues prepared from 1,8-diketones via a ring forming reaction. The new
      synthesized pi-electron donors have vinyl moieties producing extended pi-electron
      delocalization over the substituent phenyl rings at the peripheries. 

PMID- 25977715
TI  - Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver
      mediated intramolecular alkyne hydroamination reactions.
AB  - We report a synthetic methodology for the construction of the fused heterocyclic
      compounds pyrido[2,1-b]quinazolin-9(1H)-ones and pyrrolo[2,1-b]quinazolin-9(1H)
      ones through an AgOTf-catalyzed intramolecular alkyne hydroamination reaction.
      The methodology is applicable to a wide scope of substrates and produces a series
      of fused quinazolinone heterocycles in good to excellent yields. 

PMID- 25977716
TI  - Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N
      dimethylanilines with maleimides.
AB  - A novel and simple strategy for the efficient synthesis of the corresponding
      tetrahydroquinolines from N,N-dimethylanilines and maleimides using visible light
      in an air atmosphere in the presence of Eosin Y as a photocatalyst has been
      developed. The metal-free protocol involves aerobic oxidative cyclization via
      sp(3) C-H bond functionalization process to afford good yields in a one-pot
      procedure under mild conditions. 

PMID- 25977717
TI  - Ruthenium-catalyzed C-H activation of thioxanthones.
AB  - Thioxanthones - being readily available in one step from thiosalicylic acid and
      arenes - were used in ruthenium-catalyzed C-H-activation reaction to produce 1
      mono- or 1,8-disubstituted thioxanthones in good to excellent yields. Scope and
      limitation of this reaction are presented. 

PMID- 25977718
TI  - The preparation of new functionalized [2.2]paracyclophane derivatives with N
      containing functional groups.
AB  - The two isomeric bis(isocyanates) 4,12- and 4,16-di
      isocyanato[2.2]paracyclophane, 16 and 28, have been prepared from their
      corresponding diacids by simple routes. The two isomers are versatile
      intermediates for the preparation of various cyclophanes bearing substituents
      with nitrogen-containing functional groups, e.g., the pseudo-ortho diamine 8, the
      bis secondary amine 23, and the crownophanes 18 and 19. Several of these new
      cyclophane derivatives (18, 19, 22, 26, 28) have been characterized by X-ray
      structural analysis. 

PMID- 25977719
TI  - Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic
      reaction conditions: History, scope and applications.
AB  - Amino acids, whether natural, semisynthetic or synthetic, are among the most
      important and useful chiral building blocks available for organic chemical
      synthesis. In principle, they can function as inexpensive, chiral and densely
      functionalized starting materials. On the other hand, the use of amino acid
      starting materials routinely necessitates protective group chemistry, and in
      reality, large-scale preparations of even the simplest side-chain derivatives of
      many amino acids often become annoyingly strenuous due to the necessity of
      employing protecting groups, on one or more of the amino acid functionalities,
      during the synthetic sequence. However, in the case of hydroxyamino acids such as
      hydroxyproline, serine, threonine, tyrosine and 3,4-dihydroxyphenylalanine
      (DOPA), many O-acyl side-chain derivatives are directly accessible via a
      particularly expedient and scalable method not commonly applied until recently.
      Direct acylation of unprotected hydroxyamino acids with acyl halides or
      carboxylic anhydrides under appropriately acidic reaction conditions renders
      possible chemoselective O-acylation, furnishing the corresponding side-chain
      esters directly, on multigram-scale, in a single step, and without
      chromatographic purification. Assuming a certain degree of stability under acidic
      reaction conditions, the method is also applicable for a number of related
      compounds, such as various amino alcohols and the thiol-functional amino acid
      cysteine. While the basic methodology underlying this approach has been known for
      decades, it has evolved through recent developments connected to amino acid
      derived chiral organocatalysts to become a more widely recognized procedure for
      large-scale preparation of many useful side-chain derivatives of hydroxyamino
      acids and related compounds. Such derivatives are useful in peptide chemistry and
      drug development, as amino acid amphiphiles for asymmetric catalysis, and as
      amino acid acrylic precursors for preparation of catalytically active
      macromolecular networks in the form of soluble polymers, crosslinked polymer
      beads or nanoparticulate systems. The objective of the present review is to
      increase awareness of the existence and convenience of this methodology, assess
      its competitiveness compared to newer and more elaborate procedures for
      chemoselective O-acylation reactions, spur its further development, and finally
      to chronicle the informative, but poorly documented history of its development. 

PMID- 25977720
TI  - A procedure for the preparation and isolation of nucleoside-5'-diphosphates.
AB  - Tris[bis(triphenylphosphoranylidene)ammonium] pyrophosphate (PPN pyrophosphate)
      was used in the SN2 displacements of the tosylate ion from 5'-tosylnucleosides to
      afford nucleoside-5'-diphosphates. Selective precipitation permitted the direct
      isolation of nucleoside-5'-diphosphates from crude reaction mixtures. 

PMID- 25977721
TI  - Highly selective generation of vanillin by anodic degradation of lignin: a
      combined approach of electrochemistry and product isolation by adsorption.
AB  - The oxidative degradation of lignin into a variety of valuable products has been
      under investigation since the first half of the last century. Especially, the
      chance to claim this cheap, abundant and renewable source for the production of
      the important aroma chemical vanillin (1) was one of the major driving forces of
      lignin research. So far most of the developed methods fail in technical
      application since no viable concept for work-up is included. This work represents
      a combined approach of electrochemical conversion of Kraft lignin and product
      recovery by adsorption on a strongly basic anion exchange resin. Electrolysis
      conditions are optimized regarding reaction temperatures below 100  degrees C
      allowing operation of aqueous electrolytes in simple experimental set-up.
      Employing ion exchange resins gives rise to a selective removal of low molecular
      weight phenols from the strongly alkaline electrolyte without acidification and
      precipitation of remaining lignin. The latter represents a significant advantage
      compared with conventional work-up protocols of lignin solutions. 

PMID- 25977722
TI  - Further exploration of the heterocyclic diversity accessible from the allylation
      chemistry of indigo.
AB  - Diversity-directed synthesis based on the cascade allylation chemistry of indigo,
      with its embedded 2,2'-diindolic core, has resulted in rapid access to new
      examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one
      skeleton in up to 51% yield. Additionally a derivative of the novel bridged
      heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H)-one was
      produced when the olefin of the allylic substrate was terminally disubstituted.
      Further optimisation also produced viable one-pot syntheses of derivatives of the
      spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3
      s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring
      closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen
      rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl
      8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)
      dione heterocyclic system. 

PMID- 25977723
TI  - Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial
      ribonuclease tris(2-aminobenzimidazole).
AB  - Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are
      effective site-specific RNA cleavers. Their mechanism of action is independent of
      metal ions. Here we investigate conjugates with peptide nucleic acids (PNA). RNA
      degradation occurs with similar rates and substrate specificities as in
      experiments with DNA conjugates we performed earlier. Although aggregation
      phenomena are observed in some cases, proper substrate recognition is not
      compromised. While our previous synthesis of 2-aminobenzimidazoles required an
      HgO induced cyclization step, a mercury free variant is described herein. 

PMID- 25977724
TI  - 3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen
      phosphorylase inhibitors.
AB  - Glycogen phosporylase (GP) is a promising target for the control of glycaemia.
      The design of inhibitors binding at the catalytic site has been accomplished
      through various families of glucose-based derivatives such as oxadiazoles.
      Further elaboration of the oxadiazole aromatic aglycon moiety is now reported
      with 3-glucosyl-5-amino-1,2,4-oxadiazoles synthesized by condensation of a C
      glucosyl amidoxime with N,N'-dialkylcarbodiimides or Vilsmeier salts. The 5-amino
      group introduced on the oxadiazole scaffold was expected to provide better
      inhibition of GP through potential additional interactions with the enzyme's
      catalytic site; however, no inhibition was observed at 625 uM. 

PMID- 25977725
TI  - On the strong difference in reactivity of acyclic and cyclic diazodiketones with
      thioketones: experimental results and quantum-chemical interpretation.
AB  - The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC)
      and thioketones preferably occurs with Z,E-conformers and leads to the formation
      of transient thiocarbonyl ylides in two stages. The thermodynamically favorable
      further transformation of C=S ylides bearing at least one acyl group is
      identified as the 1,5-electrocyclization into 1,3-oxathioles. However, in the
      case of diazomalonates, the dominating process is 1,3-cyclization into thiiranes
      followed by their spontaneous desulfurization yielding the corresponding alkenes.
      Finally, carbocyclic diazodiketones are much less reactive under similar
      conditions due to the locked cyclic structure and are unfavorable for the 1,3
      dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This
      structure results in high, positive values of the Gibbs free energy change for
      the first stage of the cycloaddition process. 

PMID- 25977726
TI  - Synthesis and surface grafting of a beta-cyclodextrin dimer facilitating
      cooperative inclusion of 2,6-ANS.
AB  - A novel beta-cyclodextrin (beta-CD) dimer was synthesized and surface-grafted by
      click chemistry onto azide-functionalized quartz surfaces in order to introduce
      the cooperative features of the beta-CD dimer to solid surfaces. Using NMR and
      fluorescence spectroscopy, it is shown that the free beta-CD dimer forms a 1:1
      complex with the fluorescent guest molecule, 2-anilinonaphthalene-6-sulfonic acid
      (otherwise known not to form 1:2 complexes with parent beta-CD), with an apparent
      association constant of 7300 M(-1). Further, it is shown using total internal
      reflection fluorescence spectroscopy that the inclusion of the fluorescent guest
      into both cavities of the beta-CD dimer is maintained when grafted onto a solid
      surface. 

PMID- 25977727
TI  - Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines
      from aziridines.
AB  - The metal-free synthesis of 2-substituted and 2,3-disubstituted morpholines
      through a one-pot strategy is described. A simple and inexpensive ammonium
      persulfate salt enables the reaction of aziridines with halogenated alcohols to
      proceed via an SN2-type ring opening followed by cyclization of the resulting
      haloalkoxy amine. 

PMID- 25977729
TI  - Fluoride-driven 'turn on' ESPT in the binding with a novel benzimidazole-based
      sensor.
AB  - A novel fluorescence sensor (BIP) bearing NH and OH subunits displayed a highly
      selective and sensitive recognition property for fluoride over other anions.
      Fluoride-driven ESPT, poorly used in anion recognition and sensing, was suggested
      to be responsible for the fluorescence enhancement with a blue shift of 35 nm in
      the emission spectrum. 

PMID- 25977730
TI  - MicroRNA-375 plays a dual role in prostate carcinogenesis.
AB  - BACKGROUND: Prostate cancer (PCa), a highly incident and heterogeneous
      malignancy, mostly affects men from developed countries. Increased knowledge of
      the biological mechanisms underlying PCa onset and progression are critical for
      improved clinical management. MicroRNAs (miRNAs) deregulation is common in human
      cancers, and understanding how it impacts in PCa is of major importance. MiRNAs
      are mostly downregulated in cancer, although some are overexpressed, playing a
      critical role in tumor initiation and progression. We aimed to identify miRNAs
      overexpressed in PCa and subsequently determine its impact in tumorigenesis.
      RESULTS: MicroRNA expression profiling in primary PCa and morphological normal
      prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa.
      Expression of three miRNAs, not previously associated with PCa, was subsequently
      assessed in large independent sets of primary tumors, in which miR-182 and miR
      375 were validated, but not miR-32. Significantly higher expression levels of miR
      375 were depicted in patients with higher Gleason score and more advanced
      pathological stage, as well as with regional lymph nodes metastases. Forced
      expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels
      among PCa cell lines, increased apoptosis and reduced invasion ability and cell
      viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375
      expression, knockdown experiments also attenuated the malignant phenotype. Gene
      ontology analysis implicated miR-375 in several key pathways deregulated in PCa,
      including cell cycle and cell differentiation. Moreover, CCND2 was identified as
      putative miR-375 target in PCa, confirmed by luciferase assay. CONCLUSIONS: A
      dual role for miR-375 in prostate cancer progression is suggested, highlighting
      the importance of cellular context on microRNA targeting.

PMID- 25977728
TI  - Diastereoselective and enantioselective conjugate addition reactions utilizing
      alpha,beta-unsaturated amides and lactams.
AB  - The conjugate addition reaction has been a useful tool in the formation of carbon
      carbon bonds. The utility of this reaction has been demonstrated in the synthesis
      of many natural products, materials, and pharmacological agents. In the last
      three decades, there has been a significant increase in the development of
      asymmetric variants of this reaction. Unfortunately, conjugate addition reactions
      using alpha,beta-unsaturated amides and lactams remain underdeveloped due to
      their inherently low reactivity. This review highlights the work that has been
      done on both diastereoselective and enantioselective conjugate addition reactions
      utilizing alpha,beta-unsaturated amides and lactams. 

PMID- 25977731
TI  - Epigenetic reprogramming of melanoma cells by vitamin C treatment.
AB  - BACKGROUND: The loss of 5-hydroxymethylcytosine (5hmC) has been identified as a
      novel epigenetic hallmark for melanoma. One of the known mechanisms underlying
      the loss of 5hmC is the decrease in expression of ten-eleven translocation family
      dioxygenase (TET) genes, which encode enzymes that catalyze the generation of
      5hmC. Overexpressing TET2 was shown to partially reestablish a normal 5hmC
      profile in melanoma and decrease invasiveness in rodents. However, the
      feasibility to overexpress TETs in patients remains unclear. We and others have
      recently demonstrated that TETs require vitamin C as a cofactor to generate 5hmC.
      This finding prompted us to test whether vitamin C, as an alternative to
      overexpressing TETs, could rebuild 5hmC content in melanoma. RESULTS: Consistent
      with previous reports, we found that the expression of TETs was decreased in
      various melanoma cell lines. In contrast, the expressions of sodium-dependent
      vitamin C transporters (SVCTs) were down-regulated in cell lines derived from
      melanoma metastases. Treatment of vitamin C at the physiological level (0.1 mM)
      promoted the content of 5hmC in melanoma cell lines derived from different stages
      toward the level of healthy melanocytes, which was comparable to the effect of
      overexpressing TET2. Vitamin C treatment decreased the malignancy of metastatic
      A2058 cells by inhibiting migration and anchorage-independent growth, while not
      exerting any effect on the rate of proliferation. Further, vitamin C treatment
      caused alterations in genome-wide transcriptions shown by RNA-seq, predominantly
      in ArhGAP30 and genes involved in extracellular matrix remodeling, which could
      underlie the decreased malignant phenotypes. CONCLUSIONS: Our data support the
      idea that vitamin C treatment increases 5hmC content in melanoma cells, while
      causing a decrease in tumor-cell invasiveness and clonogenic growth in soft agar.
      Thus, vitamin C could be a potential epigenetic treatment for melanoma.

PMID- 25977732
TI  - A case of tuberculous endophthalmitis successfully treated with vitrectomy
      followed by antituberculous agents.
AB  - BACKGROUND: Tuberculous endophthalmitis is very rare with only 18 reports
      published worldwide and only a few cases in Japan. We report a case of
      tuberculous endophthalmitis successfully treated with vitrectomy followed by
      antituberculous agents. FINDINGS: An 81-year-old man was referred to us due to
      the exacerbation of vitreous opacity on his left eye(OS) after he had received
      the corticosteroid therapy. His best corrected visual acuity was light perception
      OS, and he had severe intraocular inflammation with fibrin formation in the
      anterior chamber and dense vitreous opacity. A chest CT showed miliary nodules
      indicating miliary tuberculosis, and pars plana vitrectomy was performed.
      Intraoperative observation showed that the vitreous cavity was filled by fibrin,
      and large elevated subretinal yellow-white lesions were present at the mid
      periphery. The patient immediately received triple antituberculous agents orally,
      and Mycobacterium tuberculosis was detected in vitreous fluids. The intraocular
      inflammation gradually decreased, and the subretinal mass regressed within 2
      weeks. CONCLUSIONS: We encountered a case of tuberculous endophthalmitis
      successfully treated with vitrectomy followed by antituberculous agents. If
      endophthalmitis is suspected in a patient with systemic tuberculosis infection,
      prompt vitrectomy along with the administration of antituberculous agents may be
      necessary.

PMID- 25977733
TI  - A Multiscale Computational Framework to Understand Vascular Adaptation.
AB  - The failure rate for vascular interventions (vein bypass grafting, arterial
      angioplasty/stenting) remains unacceptably high. Over the past two decades,
      researchers have applied a wide variety of approaches to investigate the primary
      failure mechanisms, neointimal hyperplasia and aberrant remodeling of the wall,
      in an effort to identify novel therapeutic strategies. Despite incremental
      progress, specific cause/effect linkages among the primary drivers of the
      pathology, (hemodynamic factors, inflammatory biochemical mediators, cellular
      effectors) and vascular occlusive phenotype remain lacking. We propose a
      multiscale computational framework of vascular adaptation to develop a bridge
      between theory and experimental observation and to provide a method for the
      systematic testing of relevant clinical hypotheses. Cornerstone to our model is a
      feedback mechanism between environmental conditions and dynamic tissue plasticity
      described at the cellular level with an agent based model. Our implementation (i)
      is modular, (ii) starts from basic mechano-biology principle at the cell level
      and (iii) facilitates the agile development of the model.

PMID- 25977734
TI  - A girl with a torticollis without trauma: Grisel's syndrome.

PMID- 25977735
TI  - Spontaneous hemorrhagic strokes during pregnancy: case report and review of the
      literature.
AB  - Hemorrhagic stroke is responsible for significant morbidity and mortality.
      Postpartum and pregnancy are risk period. Only urgent care in intensive care
      units may improve prognosis. We report the case of 22 years old's Morrocan, who
      presented to our department with an intense headache headset followed a few hours
      later by consciousness disorder. Clinical examination at admission has
      objectified a woman obsessed with a GCS 13, normotensive, the labstix is
      negative. A brain scan was performed showing left temporal intra parenchymal
      hematoma with ventricular flooding and subfalcine herniation. An external
      ventricular shunt was made. The patient was extubated on day 2 of
      hospitalization, with progressive neurological improvement. Concerning
      obstetrical care, the pregnancy has evolved harmoniously without any growth
      retardation or other abnormalities, with full-term vaginal delivery of a healthy
      3kg200 baby. although Hemorrhagic stroke during pregnancy is rare, the prognosis
      is reserved. An adequate care in intensive care unit is required.

PMID- 25977736
TI  - [Identification of occupational hazards in the textile industry in the Democratic
      Republic of Congo].

PMID- 25977737
TI  - [Microcystic lymphangioma].

PMID- 25977738
TI  - [Transdurale spinal hernia].

PMID- 25977739
TI  - Fordyce angiokeratoma.

PMID- 25977740
TI  - Metabolic profil in a group of obese Moroccan children enrolled in schools in the
      city of Rabat.
AB  - INTRODUCTION: To determine the metabolic profile in a group of obese children in
      Morocco. METHODS: The BMI, the waist circumference, the blood pressure and
      metabolic parameters in 73 children (37 obese and 36 normal) were compared.
      RESULTS: 80% of obese children had abdominal obesity (p <0.0001). For systolic
      blood pressure among children who have a higher value than the 95th percentile,
      85.7% were obese and 14.3% children are normal children. For diastolic blood
      pressure, 83.34% of obese children had higher diastolic blood pressure values in
      the 95th percentile and 16.6% of normal children have a higher value than the
      95th percentile (p=0.013). No obese child had hyperglycemia. The prevalence of
      metabolic syndrome was 21.6%. CONCLUSION: Obesity is number one risk of
      cardiovascular disease for children. Early detection can help for an appropriate
      care.

PMID- 25977741
TI  - Evaluation of bacteriostatic potency of expired oral paediatric antibiotics and
      implications on infant health.
AB  - INTRODUCTION: In spite of significant risks, as well as non-clinical importance
      due to loss of potency, stiff penalties against administration of expired
      medications are still not appropriately enforced by health policy makers in many
      developing countries, possibly because of little evidence to support that expired
      medications are hazardous. The purpose of this study therefore, was to
      investigate the effect of expiration dates on in vitro bacteriostatic potentials
      of oral paediatric antibiotics. METHODS: Comparative bacteriostatic potentials of
      31 expired and seven corresponding unexpired oral paediatric antibiotics were
      determined on infantile diarrhoeagenic bacteria, using a modification of agar
      well-diffusion method. RESULTS: Verall total percentage in vitro resistance rates
      against expired and unexpired paediatric antibiotics respectively were - E. coli
      (<=100% vs. <=15.9%), Klebsiella pneumoniae (<=100% vs. <=31.3%), Proteus
      mirabilis (<=91.7% vs. <=41.7%) and Staphylococcus aureus (<=100% vs. <=18.2%).
      Resistance rates of 45.5-55.8% (sulfamethoxazole + trimethoprim 5), 39.5-63.6%
      (amoxycillin 6), 46.5-54.5% (cotrimoxazole 7), 37.5-63.6% (ampicillin +
      cloxacillin 18), and higher resistance rates of >=75.0-100% were exhibited
      towards remaining expired antibiotics. Higher total resistance and multiple
      antibiotic resistance (MAR) rates were also recorded against expired antibiotics
      (45.2-93.5%) compared to unexpired antibiotics (28.6-57.2%), except for few
      strains of E. coli and Proteus mirabilis. Furthermore, unexpired paediatric
      antibiotics exhibited wider zones of inhibition towards the test diarrhoeagenic
      bacteria (>=25.0 mm diameter). CONCLUSION: This study provided preliminary
      microbiological results on the appreciable reduction in in vitro bacteriostatic
      potentials, as well as higher resistance and multiple antibiotic resistance rates
      among expired oral paediatric antibiotics on infantile diarrhoeagenic bacteria.
      Apart from less-efficacy, administration of expired antibiotics can lead to
      increased antibiotic resistance and clinical treatment failure, as well as
      adverse drug reactions.

PMID- 25977742
TI  - Epidemiology of hepatitis C: related hepatocellular carcinoma in Cameroon.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is a global public health problem.
      Hepatitis C virus (HCV) infection accounts for close to 24% of HCC in developing
      countries especially when associated with cirrhosis. There exists no vaccine
      against HCV to prevent the occurrence of HCV-related HCC. A sound knowledge of
      the epidemiology and prevention of the initial infection is vital. The aim of our
      study was to determine the epidemiologic profile of HCV-related HCC in Cameroon
      to improve its' management. METHODS: It was a prospective study of histologically
      proven HCV-related HCC seen in two University Centers in Yaounde, Cameroon from
      March 2012 to January 2013. Demographic data (age, gender), alcohol abuse
      (>80g/day), presence of cirrhosis, tobacco abuse and parenteral exposition were
      analyzed. RESULTS: Twenty-six patients with histologically proven HCV-related HCC
      were included (18 men (69.2%) and 8 women (30.8%); mean age +/- SD, 61.46+/-10.18
      years). A total of 22 (84.6%) patients had a parenteral exposition, 02 (7.7%)
      patients were alcoholics and 06 (23.1%) patients were smokers. The proportion of
      patients with cirrhosis was 69.2% against 30.8% cirrhosis-free. Patients with
      cirrhosis were relatively younger than those cirrhosis-free (mean age +/- SD,
      59.05+/-10.05 years vs 66.87+/- 8.72 years, p=0.06). HCV-related HCC was more
      prevalent in 60 years and above patients (53.8%, 95%CI: 33.4-73.4). The relative
      risk of HCC among alcoholics patients was high (RR: 1.5, 95%CI: 1.13-1.99,
      p<0.05). CONCLUSION: In Cameroon, HCV-related HCC is more prevalent among age
      older than 60 years, a finding which is relatively less to that found in western
      countries, male gender is twice more at risk than female gender and cirrhosis
      frequency is less compared to that observed elsewhere. HCV and alcohol play a
      synergistic role in the occurrence of HCC in our environment.

PMID- 25977743
TI  - [A CMV colitis revealing systemic lupus erythematosus].

PMID- 25977744
TI  - The international survey on the management of allergic rhinitis by physicians and
      patients (ISMAR).
AB  - Epidemiologic studies suggest that the prevalence of allergic rhinitis (AR) is
      rising worldwide. Several reports, in fact, indicate increasing trends in the
      prevalence of AR especially in developing countries, likely related to the
      environment and climate changes and the adoption of an urbanized Western
      lifestyle. The primary objective of the present study was to collect information
      about management in real-life settings, including a characterization of typical
      patients' profile referring to physicians, the disease features, the common
      approaches to diagnostic assessments and therapeutic decisions. This was an
      international, multicenter, cross-sectional study conducted in adults or children
      (>=6 years) suffering from rhinitis confirmed by physician's diagnosis for at
      least one year. The 234 physicians who participated in the study included a total
      of 2778 patients in Egypt, Mexico, Brazil, Colombia, Guatemala, Iran, Venezuela,
      Argentina, Israel, Kuwait and United Arab Emirates. It was found that clinical
      history was the selected tool to diagnose and categorize AR patients (97.1%),
      with less than half of patients undergoing allergy testing, may be explaining the
      scarce use of immunotherapy on management of disease. Out of 2776 patients, 93.4%
      had somehow received a recommendation to avoid allergens and irritant agent
      exposure. Notably, 91.4% were receiving at least one treatment at the time of the
      survey, mostly oral antihistamines (79.7%) and intranasal corticosteroids
      (66.3%). Oral antihistamines, intranasal steroids and decongestants were
      considered both safe and effective by patients and physicians, preferring oral
      and nasal route of administration. The ISMAR registry was designed according to
      the most accepted epidemiological recommendations, and provides interesting
      information regarding the management of rhinitis from a patient and physician
      points of view, with many similarities between the participating countries.
      Further efforts are required to better manage AR and its comorbidities. 

PMID- 25977745
TI  - Budesonide inhalation suspension versus methylprednisolone for treatment of
      moderate bronchial asthma attacks.
AB  - BACKGROUND: Owing to their side effects, administration of steroids for bronchial
      asthma attacks should be minimized. We investigated whether budesonide inhalation
      suspension (BIS) could replace intravenous steroid administration for the
      treatment of moderate bronchial asthma attacks. SUBJECTS AND METHODS: The
      subjects were children aged 5 years and younger hospitalized for moderate
      bronchial asthma attacks. Patients were randomly assigned to one of two groups:
      20 patients received methylprednisolone (mPSL) and 20 were treated with BIS. The
      mPSL group began treatment with inhalation of procaterol hydrochloride (0.3 mL)
      and disodium cromoglycate (2 mL) three times a day and systemic administration of
      mPSL (1 mg/kg) three times a day. The BIS group began treatment with inhalation
      of procaterol hydrochloride (0.3 mL) and BIS (0.5 mg) three times a day. The
      frequency of inhalations and steroid administration was adjusted according to the
      severity of symptoms. The cortisol level at discharge was measured. RESULTS:
      There were no significant differences between the two groups in terms of the
      severity of attacks and duration of management, or in terms of therapeutic
      efficacy, duration of wheezing, or period of hospitalization. The frequency of
      inhalations on days 3 to 6 of hospitalization was lower in the BIS group than in
      the mPSL group, and the cortisol level at discharge was significantly higher in
      the BIS group (13.9 +/- 6.1 MUg/dL) than in the mPSL group (8.0 +/- 2.1 MUg/dL)
      (p = 0.008). CONCLUSION: In patients with recurrent wheezing or bronchial asthma
      of <5 years, the efficacy of BIS is equivalent or better than mPSL for moderate
      bronchial asthma attacks, and in contrast to steroid treatment, BIS treatment do
      not suppress adrenocortical function.

PMID- 25977748
TI  - Behavior Genetics and the Within-Person Variability of Daily Interpersonal
      Styles: The Heritability of Flux, Spin and Pulse.
AB  - A classical twin study was used to estimate the magnitude of genetic and
      environmental influences on four measurements of within-person variability:
      dominance flux, warmth flux, spin and pulse. Flux refers to the variability of an
      individual's interpersonal dominance and warmth. Spin measures changes in the
      tone of interpersonal styles and pulse measures changes in the intensity of
      interpersonal styles. Daily reports of interpersonal styles were collected from
      494 same-sex female twins (142 monozygotic pairs and 105 dizygotic pairs) over 45
      days. For dominance flux, warmth flux, and spin, genetic effects accounted for a
      larger proportion of variance (37%, 24%, and 30%, respectively) than shared
      environmental effects (14%, 13%, 0%, respectively), with the remaining variance
      due to the non-shared environment (62%, 50%, 70% respectively). Pulse appeared to
      be primarily influenced by the non-shared environment, although conclusions about
      the contribution of familial influences were difficult to draw from this study.

PMID- 25977746
TI  - Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes:
      Reactivity of Phospholipids and Their Oxidation Derivatives.
AB  - Phospholipids play multiple and essential roles in cells, as components of
      biological membranes. Although phospholipid bilayers provide the supporting
      matrix and surface for many enzymatic reactions, their inherent reactivity and
      possible catalytic role have not been highlighted. As other biomolecules,
      phospholipids are frequent targets of nonenzymatic modifications by reactive
      substances including oxidants and glycating agents which conduct to the formation
      of advanced lipoxidation end products (ALEs) and advanced glycation end products
      (AGEs). There are some theoretical studies about the mechanisms of reactions
      related to these processes on phosphatidylethanolamine surfaces, which
      hypothesize that cell membrane phospholipids surface environment could enhance
      some reactions through a catalyst effect. On the other hand, the phospholipid
      bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen
      species (ROS). Molecular dynamics simulations performed on phospholipid bilayers
      models, which include modified phospholipids by these reactions and subsequent
      reactions that conduct to formation of ALEs and AGEs, have revealed changes in
      the molecular interactions and biophysical properties of these bilayers as
      consequence of these reactions. Then, more studies are desirable which could
      correlate the biophysics of modified phospholipids with metabolism in processes
      such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's
      disease. 

PMID- 25977747
TI  - Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence and
      In Vivo Tissue Ageing.
AB  - Several studies have employed DNA microarrays to identify gene expression
      signatures that mark human ageing; yet the features underlying this complicated
      phenomenon remain elusive. We thus conducted a bioinformatics meta-analysis on
      transcriptomics data from human cell- and biopsy-based microarrays experiments
      studying cellular senescence or in vivo tissue ageing, respectively. We report
      that coregulated genes in the postmitotic muscle and nervous tissues are
      classified into pathways involved in cancer, focal adhesion, actin cytoskeleton,
      MAPK signalling, and metabolism regulation. Genes that are differentially
      regulated during cellular senescence refer to pathways involved in
      neurodegeneration, focal adhesion, actin cytoskeleton, proteasome, cell cycle,
      DNA replication, and oxidative phosphorylation. Finally, we revealed genes and
      pathways (referring to cancer, Huntington's disease, MAPK signalling, focal
      adhesion, actin cytoskeleton, oxidative phosphorylation, and metabolic
      signalling) that are coregulated during cellular senescence and in vivo tissue
      ageing. The molecular commonalities between cellular senescence and tissue ageing
      are also highlighted by the fact that pathways that were overrepresented
      exclusively in the biopsy- or cell-based datasets are modules either of the same
      reference pathway (e.g., metabolism) or of closely interrelated pathways (e.g.,
      thyroid cancer and melanoma). Our reported meta-analysis has revealed novel age
      related genes, setting thus the basis for more detailed future functional
      studies. 

PMID- 25977749
TI  - Spindle assembly checkpoint is sufficient for complete Cdc20 sequestering in
      mitotic control.
AB  - The spindle checkpoint assembly (SAC) ensures genome fidelity by temporarily
      delaying anaphase onset, until all chromosomes are properly attached to the
      mitotic spindle. The SAC delays mitotic progression by preventing activation of
      the ubiquitin ligase anaphase-promoting complex (APC/C) or cyclosome; whose
      activation by Cdc20 is required for sister-chromatid separation marking the
      transition into anaphase. The mitotic checkpoint complex (MCC), which contains
      Cdc20 as a subunit, binds stably to the APC/C. Compelling evidence by Izawa and
      Pines (Nature 2014; 10.1038/nature13911) indicates that the MCC can inhibit a
      second Cdc20 that has already bound and activated the APC/C. Whether or not MCC
      per se is sufficient to fully sequester Cdc20 and inhibit APC/C remains unclear.
      Here, a dynamic model for SAC regulation in which the MCC binds a second Cdc20
      was constructed. This model is compared to the MCC, and the MCC-and-BubR1 (dual
      inhibition of APC) core model variants and subsequently validated with
      experimental data from the literature. By using ordinary nonlinear differential
      equations and spatial simulations, it is shown that the SAC works sufficiently to
      fully sequester Cdc20 and completely inhibit APC/C activity. This study
      highlights the principle that a systems biology approach is vital for molecular
      biology and could also be used for creating hypotheses to design future
      experiments. 

PMID- 25977752
TI  - Seroprevalence of Hepatitis E virus infection in the Irish pig population.
AB  - BACKGROUND: Hepatitis E is an acute viral disease of humans, occurring in
      explosive outbreaks in the developing world and as sporadic cases in returning
      travellers. Increasing recognition of indigenous transmission in Western
      countries suggests a zoonotic source of infection, most likely pigs. To determine
      if hepatitis E virus is present in Irish pigs, sera from 330 animals were
      examined for antibodies using a commercially available ELISA. FINDINGS:
      Antibodies were detected in 89 pigs (27%) in 13 herds (81%). CONCLUSIONS:
      Hepatitis E virus is present in most Irish pig herds and in many animals within
      these herds.

PMID- 25977750
TI  - Utility of five commonly used immunohistochemical markers TTF-1, Napsin A, CK7,
      CK5/6 and P63 in primary and metastatic adenocarcinoma and squamous cell
      carcinoma of the lung: a retrospective study of 246 fine needle aspiration cases.
AB  - BACKGROUND: Fine needle aspiration (FNA) biopsy plays a critical role in the
      diagnosis and staging of lung primary and metastatic lung carcinoma. Accurate
      subclassification of adenocarcinoma (ADC) and/or squamous cell carcinoma (SqCC)
      is crucial for the targeted therapy. However, the distinction between ADC and
      SqCC may be difficult in small FNA specimens. Here, we have retrospectively
      evaluated the utility of TTF-1, Napsin A, CK7, P63 and CK5/6 immunohistochemical
      (IHC) markers in the distinguishing and subclassification of ADC and SqCC.
      METHODS: A total of 246 FNA cases were identified by a computer search over a two
      year period, including 102 primary NSCLC and 144 primary NSCLC which had
      metastasized to other sites. The immunostaining patterns of TTF-1, Napsin A, CK7,
      P63 and CK5/6 were correlated with the histological diagnosis of the tumor.
      RESULTS: In 72 primary ADCs, TTF-1, Napsin A and CK7 showed a sensitivity and
      specificity of 84.5%/96.4%, 92.0%/100%, and 93.8%/50.0%. In 30 primary SqCCs,
      CK5/6 and P63 showed a sensitivity and specificity of 100%/77.8% and 91.7%/78.3%.
      In 131 metastatic ADCs, Napsin A showed the highest specificity (100%), versus
      TTF-1 (87.5%) and CK7 (25%) but decreased sensitivity (67.8% versus 86.9% and
      100%); whereas in 13 metastatic SqCCs, CK5/6 and P63 showed a
      sensitivity/specificity of 100%/84.6% and 100%/68.4%. Bootstrap analysis showed
      that the combination of TTF-1/CK7, TTF-1/Napsin A and TTF-1/CK7/Napsin A had a
      sensitivity/specificity of 0.960/0.732, 0.858/0.934, 0.972/0.733 for primary lung
      ADCs and 0.992/0.642, 0.878/0.881, 0.993/0.618 for metastatic lung ADCs.
      CONCLUSIONS: Our study demonstrated that IHC markers had variable sensitivity and
      specificity in the subclassification of primary and metastatic ADC and SqCC.
      Based on morphological findings, an algorithm with the combination use of markers
      aided in the subclassification of NSCLCs in difficult cases.

PMID- 25977751
TI  - Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin
      1 expression in airway smooth muscle in a guinea pig asthma model.
AB  - BACKGROUND: Caveolin-1 is a fundamental signalling scaffold protein involved in
      contraction; however, the role of caveolin-1 in airway responsiveness remains
      unclear. We evaluated the relationship between caveolin-1 expression in airway
      smooth muscle (ASM) and antigen-induced airway responsiveness and obstruction in
      a guinea pig asthma model. METHODS: Airway obstruction in sensitised guinea pigs,
      induced by antigenic (ovalbumin) challenges administered every 10 days, was
      measured. Antigen-induced responsiveness to histamine and the expression of
      caveolin-1 and cavin 1, 2 and 3 were evaluated at the third ovalbumin challenge.
      The control group received saline solution instead of ovalbumin. RESULTS: After
      the first challenge, antigen exposure induced a transient airway obstruction and
      airway hyperresponsiveness, high levels of IL-4 and IL-5 in lung and airway
      globet cells proliferation at the third antigenic challenge. Caveolin-1 mRNA
      levels in total lung decreased in the experimental group compared with controls.
      Flow cytometric analysis of ASM from the experimental group showed a high number
      of cells expressing caveolin-1 compared with controls. This increase was
      confirmed by western blot. Airway obstruction and hyperresponsiveness correlated
      with the degree of increased caveolin-1 expression in ASM cells (P < 0.05; r =
      0.69 and -0.52, respectively). The expression of cavins 1, 2 and 3 in ASM also
      increased in the experimental group compared to controls. Immunohistochemical
      findings reveal that differences in ASM caveolin-1 were not evident between
      groups. Nevertheless, a marked decrease in caveolin-1 and caspase 3 was observed
      in the pulmonary vascular smooth muscle of asthma model compared with controls.
      Histological analysis did not reveal differences in smooth muscles mass or
      subepithelial fibrosis levels in airways between groups. However, an enlargement
      of smooth muscle mass was observed in the pulmonary microvessels of experimental
      animals. This enlargement did not induce changes in pulmonary or systemic
      arterial pressures. CONCLUSIONS: Our data suggest that caveolin-1 expression in
      ASM has a crucial role in the development of antigen-induced airway obstruction
      and hyperresponsiveness in a guinea pig asthma model. In addition, the asthma
      model in guinea pigs appears to induce a contractile smooth muscle phenotype in
      the airways and a proliferative smooth muscle phenotype in pulmonary vessels.

PMID- 25977753
TI  - Ant-App-DB: a smart solution for monitoring arthropods activities, experimental
      data management and solar calculations without GPS in behavioral field studies.
AB  - Field studies on arthropod ecology and behaviour require simple and robust
      monitoring tools, preferably with direct access to an integrated database. We
      have developed and here present a database tool allowing smart-phone based
      monitoring of arthropods. This smart phone application provides an easy solution
      to collect, manage and process the data in the field which has been a very
      difficult task for field biologists using traditional methods. To monitor our
      example species, the desert ant Cataglyphis fortis, we considered behavior, nest
      search runs, feeding habits and path segmentations including detailed information
      on solar position and Azimuth calculation, ant orientation and time of day. For
      this we established a user friendly database system integrating the Ant-App-DB
      with a smart phone and tablet application, combining experimental data
      manipulation with data management and providing solar position and timing
      estimations without any GPS or GIS system. Moreover, the new desktop application
      Dataplus allows efficient data extraction and conversion from smart phone
      application to personal computers, for further ecological data analysis and
      sharing. All features, software code and database as well as Dataplus application
      are made available completely free of charge and sufficiently generic to be
      easily adapted to other field monitoring studies on arthropods or other migratory
      organisms. The software applications Ant-App-DB and Dataplus described here are
      developed using the Android SDK, Java, XML, C# and SQLite Database. 

PMID- 25977754
TI  - Challenges and opportunities for early-career Teaching-Focussed academics in the
      biosciences.
AB  - Twenty-seven percent of academics in UK Higher Education (HE) are in Teaching
      Focussed positions, making major contributions to undergraduate programmes in an
      era of high student expectations when it comes to teaching quality. However,
      institutional support for Teaching-Focussed academics is often limited, both in
      terms of peer networking and opportunities for career development. As four early
      career stage Teaching-Focussed academics working in a variety of institutions, we
      explore what motivated our choices to make teaching our primary academic
      activity, and the challenges that we have faced in doing so. In addition to
      highlighting the need for universities to fully recognise the achievements of
      teaching staff, we discuss the role that the various biosciences learned
      societies have in supporting Teaching-Focussed academics. We identify that there
      is a need for the learned societies to come together and pool their expertise in
      this area. The fragmented nature of the Teaching-Focussed academic community
      means that clear sources of national support are needed in order to best enable
      the next generation of bioscience educators to reach their full potential. 

PMID- 25977756
TI  - I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis.
AB  - Evidence demonstrating that regular ingestion of coffee has salutary effects on
      patients with chronic liver disease is accumulating rapidly. Specifically, it
      appears that coffee ingestion can slow the progression of liver fibrosis,
      preventing cirrhosis and hepatocellular carcinoma (HCC). This should excite
      clinicians and scientists alike, since these observations, if true, would create
      effective, testable hypotheses that should lead to improved understanding on
      fibrosis pathogenesis and thus may generate novel pharmacologic treatments of
      patients with chronic liver disease. This review is designed to examine the
      relevant clinical and epidemiological data in critical fashion and to examine the
      putative pharmacological effects of coffee relevant to the pathogenesis of liver
      fibrosis and cirrhosis. We hope that this will inspire relevant critical
      analyses, especially among "coffee skeptics". Of note, one major assumption made
      by this review is that the bulk of the effects of coffee consumption are mediated
      by caffeine, rather than by other chemical constituents of coffee. Our rationales
      for this assumption are threefold: first, caffeine's effects on adenosinergic
      signaling provide testable hypotheses; second, although there are  myriad
      chemical constituents of coffee, they are present in very low concentrations, and
      perhaps more importantly, vary greatly between coffee products and production
      methods (it is important to note that we do not dismiss the "botanical"
      hypothesis here; rather, we do not emphasize it at present due to the limitations
      of the studies examined); lastly, some (but not all) observational studies have
      examined both coffee and non-coffee caffeine consumption and found consistent
      effects, and when examined, no benefit to decaffeinated coffee has been observed.
      Further, in the interval since we examined this phenomenon last, further evidence
      has accumulated supporting caffeine as the effector molecule for coffee's
      salutary effects. 

PMID- 25977755
TI  - Portrayed emotions in the movie "Forrest Gump".
AB  - Here we present a dataset with a description of portrayed emotions in the movie
      "Forrest Gump". A total of 12 observers independently annotated emotional
      episodes regarding their temporal location and duration. The nature of an emotion
      was characterized with basic attributes, such as arousal and valence, as well as
      explicit emotion category labels. In addition, annotations include a record of
      the perceptual evidence for the presence of an emotion. Two variants of the movie
      were annotated separately: 1) an audio-movie version of Forrest Gump that has
      been used as a stimulus for the acquisition of a large public functional brain
      imaging dataset, and 2) the original audio-visual movie. We present reliability
      and consistency estimates that suggest that both stimuli can be used to study
      visual and auditory emotion cue processing in real-life like situations. Raw
      annotations from all observers are publicly released in full in order to maximize
      their utility for a wide range of applications and possible future extensions. In
      addition, aggregate time series of inter-observer agreement with respect to
      particular attributes of portrayed emotions are provided to facilitate adoption
      of these data. 

PMID- 25977757
TI  - How efficient is patient discharge following lower limb arthroplasty?
AB  - BACKGROUND: Appropriately timed patient discharge is essential for optimal
      patient care and efficient hospital functioning. The post-operative morbidity
      survey (POMS) is the only validated prospective method of measuring short-term
      post-operative morbidity. It has not previously been used as a bed utilisation
      tool. METHODS: We collected POMS data from 529 consecutive lower-limb
      arthroplasty patients over a 1-year period and recorded the number of patients
      remaining in the hospital without morbidity, together with alternative reasons
      for remaining in hospital. Data was collected on post-operative days (POD) 3, 5,
      8 and 15. RESULTS: On POD 3, 45% of hip arthroplasty patients and 52% of knee
      arthroplasty patients remained in hospital with no identifiable morbidity. On POD
      5, 53% of hip arthroplasty patients and 47% of knee arthroplasty patients
      remained in hospital with no identifiable morbidity. These figures declined by
      POD 8 and 15. The most common reason for inappropriate bed occupancy was ongoing
      physiotherapy and occupational therapy. CONCLUSIONS: We believe POMS is able to
      identify patients remaining in hospital with no significant morbidity and has
      utility as a prospective bed utilisation tool. Addition of a mobility measure to
      POMS may improve its utility in detecting morbidity requiring hospitalisation,
      particularly following lower limb arthroplasty.

PMID- 25977758
TI  - Study protocol of the SWORD-study: a randomised controlled trial comparing
      combined online and face-to-face cognitive behaviour therapy versus treatment as
      usual in managing fear of cancer recurrence.
AB  - BACKGROUND: Fear of cancer recurrence (FCR) is one of the most frequently cited
      problems by cancer survivors. More than one third report high FCR, which is a
      clinical concern due to its association with negative health outcomes. The aim of
      the current study is to evaluate the efficacy of cognitive behaviour therapy
      (CBT) in reducing FCR in high fearful cancer survivors. METHODS/DESIGN: The SWORD
      study has a randomised controlled design with two arms. A sample of 104 high
      fearful cancer survivors (breast, prostate or colorectal cancer) will be
      recruited from local hospitals. Cancer survivors will be randomised to receive
      CBT (intervention condition) or treatment as usual (control condition). For those
      in the intervention condition, the therapy will be individually delivered in a
      combination of 5 face-to-face therapy sessions and 3 online or telephone sessions
      by a trained therapist. Furthermore, these survivors will have access to a
      supportive website (or workbook) throughout the therapy. Survivors in the control
      condition will not receive the intervention and will not have access to the
      website. The primary outcome will be severity of fear of recurrence (Cancer Worry
      Scale). Quality of life (EORTC Quality of Life Questionnaire Core 30) and general
      psychological wellbeing will be assessed as secondary outcomes. Assessments will
      take place at baseline (before random assignment), at 3, 9 and 15 months after
      the baseline assessment. The study has been approved by an ethical review board.
      DISCUSSION: If the intervention proves to be effective an evidence-based therapy
      to manage high FCR will become available for use in clinical practice.

PMID- 25977759
TI  - Global integrated drought monitoring and prediction system.
AB  - Drought is by far the most costly natural disaster that can lead to widespread
      impacts, including water and food crises. Here we present data sets available
      from the Global Integrated Drought Monitoring and Prediction System (GIDMaPS),
      which provides drought information based on multiple drought indicators. The
      system provides meteorological and agricultural drought information based on
      multiple satellite-, and model-based precipitation and soil moisture data sets.
      GIDMaPS includes a near real-time monitoring component and a seasonal
      probabilistic prediction module. The data sets include historical drought
      severity data from the monitoring component, and probabilistic seasonal forecasts
      from the prediction module. The probabilistic forecasts provide essential
      information for early warning, taking preventive measures, and planning
      mitigation strategies. GIDMaPS data sets are a significant extension to current
      capabilities and data sets for global drought assessment and early warning. The
      presented data sets would be instrumental in reducing drought impacts especially
      in developing countries. Our results indicate that GIDMaPS data sets reliably
      captured several major droughts from across the globe. 

PMID- 25977760
TI  - The systematic identification of cytoskeletal genes required for Drosophila
      melanogaster muscle maintenance.
AB  - Animal muscles must maintain their function and structure while bearing
      substantial mechanical loads. How muscles withstand persistent mechanical strain
      is presently not well understood. Understanding the mechanisms by which tissues
      maintain their complex architecture is a key goal of cell biology. This dataset
      represents a systematic screen through the Drosophila melanogaster cytoskeleton
      to identify genes that are required to maintain tissue, specifically muscle,
      architecture. Using RNA interference (RNAi), we knocked down 238 genes in
      Drosophila and assayed for climbing ability with a robust behavioural assay. Here
      we present the summary of the screen and provide the complete results of the
      assays. We have uncovered a number of novel hits that would reward further study.
      The data are easy to use: the raw data are provided to allow researchers to
      perform their own analysis and analysed results are given indicating whether or
      not the genes are required for muscle maintenance. This dataset will allow other
      researchers to identify candidate genes for more detailed study and lead to
      better understanding of muscle maintenance. 

PMID- 25977761
TI  - A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an
      audio movie.
AB  - Here we present a high-resolution functional magnetic resonance (fMRI) dataset -
      20 participants recorded at high field strength (7 Tesla) during prolonged
      stimulation with an auditory feature film ("Forrest Gump"). In addition, a
      comprehensive set of auxiliary data (T1w, T2w, DTI, susceptibility-weighted
      image, angiography) as well as measurements to assess technical and physiological
      noise components have been acquired. An initial analysis confirms that these data
      can be used to study common and idiosyncratic brain response patterns to complex
      auditory stimulation. Among the potential uses of this dataset are the study of
      auditory attention and cognition, language and music perception, and social
      perception. The auxiliary measurements enable a large variety of additional
      analysis strategies that relate functional response patterns to structural
      properties of the brain. Alongside the acquired data, we provide source code and
      detailed information on all employed procedures - from stimulus creation to data
      analysis. In order to facilitate replicative and derived works, only free and
      open-source software was utilized. 

PMID- 25977762
TI  - A global compendium of human dengue virus occurrence.
AB  - A global geographic database of human dengue virus occurrence was produced to
      generate a global risk map and associated burden estimates(1). Herein we present
      the database, which comprises occurrence data linked to point or polygon
      locations, derived from peer-reviewed literature and case reports as well as
      informal online sources. Entries date from 1960 to 2012. We describe all data
      collection processes in full, as well as geo-positioning, database management and
      quality-control procedures. This is the most comprehensive database of confirmed
      human dengue infection to-date, consisting of 8,309 geo-positioned occurrences in
      total. 

PMID- 25977763
TI  - miRNA expression atlas in male rat.
AB  - MicroRNAs (miRNAs) are small (~22 nucleotide) noncoding RNAs that play pivotal
      roles in regulation of gene expression. The value of miRNAs as circulating
      biomarkers is now broadly recognized; such tissue-specific biomarkers can be used
      to monitor tissue injury and several pathophysiological conditions in organs. In
      addition, miRNA profiles of normal organs and tissues are important for obtaining
      a better understanding of the source of modulated miRNAs in blood and how those
      modulations reflect various physiological and toxicological conditions. This work
      was aimed at creating an miRNA atlas in rats, as part of a collaborative effort
      with the Toxicogenomics Informatics Project in Japan (TGP2). We analyzed genome
      wide miRNA profiles of 55 different organs and tissues obtained from normal male
      rats using miRNA arrays. The work presented herein represents a comprehensive
      dataset derived from normal samples profiled in a single study. Here we present
      the whole dataset with miRNA profiles of multiple organs, as well as precise
      information on experimental procedures and organ-specific miRNAs identified in
      this dataset. 

PMID- 25977764
TI  - Microclim: Global estimates of hourly microclimate based on long-term monthly
      climate averages.
AB  - The mechanistic links between climate and the environmental sensitivities of
      organisms occur through the microclimatic conditions that organisms experience.
      Here we present a dataset of gridded hourly estimates of typical microclimatic
      conditions (air temperature, wind speed, relative humidity, solar radiation, sky
      radiation and substrate temperatures from the surface to 1 m depth) at high
      resolution (~15 km) for the globe. The estimates are for the middle day of each
      month, based on long-term average macroclimates, and include six shade levels and
      three generic substrates (soil, rock and sand) per pixel. These data are suitable
      for deriving biophysical estimates of the heat, water and activity budgets of
      terrestrial organisms. 

PMID- 25977765
TI  - Systematic global assessment of reef fish communities by the Reef Life Survey
      program.
AB  - The assessment of patterns in macroecology, including those most relevant to
      global biodiversity conservation, has been hampered by a lack of quantitative
      data collected in a consistent manner over the global scale. Global analyses of
      species' abundance data typically rely on records aggregated from multiple
      studies where different sampling methods and varying levels of taxonomic and
      spatial resolution have been applied. Here we describe the Reef Life Survey (RLS)
      reef fish dataset, which contains 134,759 abundance records, of 2,367 fish taxa,
      from 1,879 sites in coral and rocky reefs distributed worldwide. Data were
      systematically collected using standardized methods, offering new opportunities
      to assess broad-scale spatial patterns in community structure. The development of
      such a large dataset was made possible through contributions of investigators
      associated with science and conservation agencies worldwide, and the assistance
      of a team of over 100 recreational SCUBA divers, who undertook training in
      scientific techniques for underwater surveys and voluntarily contributed skills,
      expertise and their time to data collection. 

PMID- 25977766
TI  - Time-resolved gene expression profiling during reprogramming of C/EBPalpha-pulsed
      B cells into iPS cells.
AB  - The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is
      lengthy and inefficient. The development of a reprogramming system that allows
      rapid and synchronous reprogramming to pluripotency is imperative for
      understanding the mechanism of iPSC formation and for future therapeutic
      applications. We have recently reported that a short expression in mouse primary
      B cells of the transcription factor C/EBPalpha before the induction of
      pluripotency factors increases the iPSC reprogramming efficiency >100-fold,
      involving 95% of the cells within a week. Here we present a dataset containing
      the time course of gene expression during this process as determined by
      microarray and RNA-seq techniques. 

PMID- 25977767
TI  - The species translation challenge-a systems biology perspective on human and rat
      bronchial epithelial cells.
AB  - The biological responses to external cues such as drugs, chemicals, viruses and
      hormones, is an essential question in biomedicine and in the field of toxicology,
      and cannot be easily studied in humans. Thus, biomedical research has
      continuously relied on animal models for studying the impact of these compounds
      and attempted to 'translate' the results to humans. In this context, the SBV
      IMPROVER (Systems Biology Verification for Industrial Methodology for PROcess
      VErification in Research) collaborative initiative, which uses crowd-sourcing
      techniques to address fundamental questions in systems biology, invited
      scientists to deploy their own computational methodologies to make predictions on
      species translatability. A multi-layer systems biology dataset was generated that
      was comprised of phosphoproteomics, transcriptomics and cytokine data derived
      from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in
      parallel to more than 50 different stimuli under identical conditions. The
      present manuscript describes in detail the experimental settings, generation,
      processing and quality control analysis of the multi-layer omics dataset
      accessible in public repositories for further intra- and inter-species
      translation studies. 

PMID- 25977768
TI  - More bang for your byte.

PMID- 25977769
TI  - Genomes and phenomes of a population of outbred rats and its progenitors.
AB  - Finding genetic variants that contribute to phenotypic variation is one of the
      main challenges of modern genetics. We used an outbred population of rats
      (Heterogeneous Stock, HS) in a combined sequence-based and genetic mapping
      analysis to identify sequence variants and genes contributing to complex traits
      of biomedical relevance. Here we describe the sequences of the eight inbred
      progenitors of the HS and the variants that segregate between them. We report the
      genotyping of 1,407 HS rats, and the collection from 2,006 rats of 195 phenotypic
      measures that are relevant to models of anxiety, type 2 diabetes, hypertension
      and osteoporosis. We make available haplotype dosages for the 1,407 genotyped
      rats, since genetic mapping in the HS is best carried out by reconstructing each
      HS chromosome as a mosaic of the progenitor genomes. Finally, we have deposited
      an R object that makes it easy to incorporate our sequence data into any genetic
      study of HS rats. Our genetic data are available for both Rnor3.4 and Rnor5.0 rat
      assemblies. 

PMID- 25977770
TI  - Direct infusion mass spectrometry metabolomics dataset: a benchmark for data
      processing and quality control.
AB  - Direct-infusion mass spectrometry (DIMS) metabolomics is an important approach
      for characterising molecular responses of organisms to disease, drugs and the
      environment. Increasingly large-scale metabolomics studies are being conducted,
      necessitating improvements in both bioanalytical and computational workflows to
      maintain data quality. This dataset represents a systematic evaluation of the
      reproducibility of a multi-batch DIMS metabolomics study of cardiac tissue
      extracts. It comprises of twenty biological samples (cow vs. sheep) that were
      analysed repeatedly, in 8 batches across 7 days, together with a concurrent set
      of quality control (QC) samples. Data are presented from each step of the
      workflow and are available in MetaboLights. The strength of the dataset is that
      intra- and inter-batch variation can be corrected using QC spectra and the
      quality of this correction assessed independently using the repeatedly-measured
      biological samples. Originally designed to test the efficacy of a batch
      correction algorithm, it will enable others to evaluate novel data processing
      algorithms. Furthermore, this dataset serves as a benchmark for DIMS
      metabolomics, derived using best-practice workflows and rigorous quality
      assessment. 

PMID- 25977771
TI  - Comprehensive RNA-Seq transcriptomic profiling across 11 organs, 4 ages, and 2
      sexes of Fischer 344 rats.
AB  - The rat is used extensively by the pharmaceutical, regulatory, and academic
      communities for safety assessment of drugs and chemicals and for studying human
      diseases; however, its transcriptome has not been well studied. As part of the
      SEQC (i.e., MAQC-III) consortium efforts, a comprehensive RNA-Seq data set was
      constructed using 320 RNA samples isolated from 10 organs (adrenal gland, brain,
      heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from
      both sexes of Fischer 344 rats across four ages (2-, 6-, 21-, and 104-week-old)
      with four biological replicates for each of the 80 sample groups (organ-sex-age).
      With the Ribo-Zero rRNA removal and Illumina RNA-Seq protocols, 41 million 50 bp
      single-end reads were generated per sample, yielding a total of 13.4 billion
      reads. This data set could be used to identify and validate new rat genes and
      transcripts, develop a more comprehensive rat transcriptome annotation system,
      identify novel gene regulatory networks related to tissue specific gene
      expression and development, and discover genes responsible for disease and drug
      toxicity and efficacy. 

PMID- 25977772
TI  - Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the
      chick embryo.
AB  - The anteroposterior compartments of the developing hindbrain (rhombomeres [r])
      are normally patterned by the combinatorial action of distinct Hox genes. Using
      Affymetrix GeneChips to define the repertoire of genes regulated in each
      rhombomere, we have performed a systematic survey of the transcriptional status
      of individual segments of the developing chick hindbrain (r1-5) at a key stage of
      early development (HH11) and identified hundreds of previously un-described genes
      expressed in this region. For comparative purposes, we have also included the
      adjacent region of the embryonic midbrain (m) in our dataset. In summary, six
      different embryonic brain regions (m, r1, r2, r3, r4 & r5) are represented by
      biological duplicates to give a raw dataset comprised of 12 individual Affymetrix
      GeneChip Cel and CHP files. These data give an opportunity to assess the genome
      wide complexity of gene expression during patterning of the chick developing
      midbrain and hindbrain, and may be relevant to extending our understanding of the
      genes regulated by Hox family transcription factors. 

PMID- 25977773
TI  - Tree of Sex: a database of sexual systems.
AB  - The vast majority of eukaryotic organisms reproduce sexually, yet the nature of
      the sexual system and the mechanism of sex determination often vary remarkably,
      even among closely related species. Some species of animals and plants change sex
      across their lifespan, some contain hermaphrodites as well as males and females,
      some determine sex with highly differentiated chromosomes, while others determine
      sex according to their environment. Testing evolutionary hypotheses regarding the
      causes and consequences of this diversity requires interspecific data placed in a
      phylogenetic context. Such comparative studies have been hampered by the lack of
      accessible data listing sexual systems and sex determination mechanisms across
      the eukaryotic tree of life. Here, we describe a database developed to facilitate
      access to sexual system and sex chromosome information, with data on sexual
      systems from 11,038 plant, 705 fish, 173 amphibian, 593 non-avian reptilian, 195
      avian, 479 mammalian, and 11,556 invertebrate species. 

PMID- 25977774
TI  - Genome-wide functional genomic and transcriptomic analyses for genes regulating
      sensitivity to vorinostat.
AB  - Identification of mechanisms of resistance to histone deacetylase inhibitors,
      such as vorinostat, is important in order to utilise these anticancer compounds
      more efficiently in the clinic. Here, we present a dataset containing multiple
      tiers of stringent siRNA screening for genes that when knocked down conferred
      sensitivity to vorinostat-induced cell death. We also present data from a miRNA
      overexpression screen for miRNAs contributing to vorinostat sensitivity.
      Furthermore, we provide transcriptomic analysis using massively parallel
      sequencing upon knockdown of 14 validated vorinostat-resistance genes. These
      datasets are suitable for analysis of genes and miRNAs involved in cell death in
      the presence and absence of vorinostat as well as computational biology
      approaches to identify gene regulatory networks. 

PMID- 25977775
TI  - The Clodia database: a long time series of fishery data from the Adriatic Sea.
AB  - Long-term time series of species abundances can depict population declines and
      changes in communities in response to anthropogenic activities, climate changes,
      alterations of trophic relationships. Here we present a database of historical
      marine fishery landing data, covering a remarkably long time series (1945-2013)
      and referring to one of the most exploited areas of the Mediterranean Sea, the
      Adriatic Sea. The database includes two time series of landing data, 1945-2013
      and 1997-2013, from the official statistics of the fish market of Chioggia, where
      the major fishing fleet of the area operates. Comparisons between the landing
      data of the database and landing data from other fisheries or data from
      scientific surveys support the reliability of the time series in depicting
      changes in species abundances. The database is expected to be used by fishery
      biologists and ecologists interested in depicting and understanding temporal
      variations in species abundances and community composition, in relation to
      environmental and anthropogenic factors. 

PMID- 25977776
TI  - Life history profiles for 27 strepsirrhine primate taxa generated using captive
      data from the Duke Lemur Center.
AB  - Since its establishment in 1966, the Duke Lemur Center (DLC) has accumulated
      detailed records for nearly 4,200 individuals from over 40 strepsirrhine primate
      taxa-the lemurs, lorises, and galagos. Here we present verified data for 3,627
      individuals of 27 taxa in the form of a life history table containing summarized
      species values for variables relating to ancestry, reproduction, longevity, and
      body mass, as well as the two raw data files containing direct and calculated
      variables from which this summary table is built. Large sample sizes,
      longitudinal data that in many cases span an animal's entire life, exact dates of
      events, and large numbers of individuals from closely related yet biologically
      diverse primate taxa make these datasets unique. This single source for verified
      raw data and systematically compiled species values, particularly in combination
      with the availability of associated biological samples and the current live
      colony for research, will support future studies from an enormous spectrum of
      disciplines. 

PMID- 25977777
TI  - Cross-platform ultradeep transcriptomic profiling of human reference RNA samples
      by RNA-Seq.
AB  - Whole-transcriptome sequencing ('RNA-Seq') has been drastically changing the
      scale and scope of genomic research. In order to fully understand the power and
      limitations of this technology, the US Food and Drug Administration (FDA)
      launched the third phase of the MicroArray Quality Control (MAQC-III) project,
      also known as the SEquencing Quality Control (SEQC) project. Using two well
      established human reference RNA samples from the first phase of the MAQC project,
      three sequencing platforms were tested across more than ten sites with built-in
      truths including spike-in of external RNA controls (ERCC), titration data and
      qPCR verification. The SEQC project generated over 30 billion sequence reads
      representing the largest RNA-Seq data ever generated by a single project on
      individual RNA samples. This extraordinarily ultradeep transcriptomic data set
      and the known truths built into the study design provide many opportunities for
      further research and development to advance the improvement and application of
      RNA-Seq. 

PMID- 25977778
TI  - Transcriptomic profiling of rat liver samples in a comprehensive study design by
      RNA-Seq.
AB  - RNA-Seq provides the capability to characterize the entire transcriptome in
      multiple levels including gene expression, allele specific expression,
      alternative splicing, fusion gene detection, and etc. The US FDA-led SEQC (i.e.,
      MAQC-III) project conducted a comprehensive study focused on the transcriptome
      profiling of rat liver samples treated with 27 chemicals to evaluate the utility
      of RNA-Seq in safety assessment and toxicity mechanism elucidation. The chemicals
      represented multiple chemogenomic modes of action (MOA) and exhibited varying
      degrees of transcriptional response. The paired-end 100 bp sequencing data were
      generated using Illumina HiScanSQ and/or HiSeq 2000. In addition to the core
      study, six animals (i.e., three aflatoxin B1 treated rats and three vehicle
      control rats) were sequenced three times, with two separate library preparations
      on two sequencing machines. This large toxicogenomics dataset can serve as a
      resource to characterize various aspects of transcriptomic changes (e.g.,
      alternative splicing) that are byproduct of chemical perturbation. 

PMID- 25977779
TI  - Quantum chemistry structures and properties of 134 kilo molecules.
AB  - Computational de novo design of new drugs and materials requires rigorous and
      unbiased exploration of chemical compound space. However, large uncharted
      territories persist due to its size scaling combinatorially with molecular size.
      We report computed geometric, energetic, electronic, and thermodynamic properties
      for 134k stable small organic molecules made up of CHONF. These molecules
      correspond to the subset of all 133,885 species with up to nine heavy atoms
      (CONF) out of the GDB-17 chemical universe of 166 billion organic molecules. We
      report geometries minimal in energy, corresponding harmonic frequencies, dipole
      moments, polarizabilities, along with energies, enthalpies, and free energies of
      atomization. All properties were calculated at the B3LYP/6-31G(2df,p) level of
      quantum chemistry. Furthermore, for the predominant stoichiometry, C7H10O2, there
      are 6,095 constitutional isomers among the 134k molecules. We report energies,
      enthalpies, and free energies of atomization at the more accurate G4MP2 level of
      theory for all of them. As such, this data set provides quantum chemical
      properties for a relevant, consistent, and comprehensive chemical space of small
      organic molecules. This database may serve the benchmarking of existing methods,
      development of new methods, such as hybrid quantum mechanics/machine learning,
      and systematic identification of structure-property relationships. 

PMID- 25977780
TI  - Comprehensive analysis of the venom gland transcriptome of the spider Dolomedes
      fimbriatus.
AB  - A comprehensive transcriptome analysis of an expressed sequence tag (EST)
      database of the spider Dolomedes fimbriatus venom glands using single-residue
      distribution analysis (SRDA) identified 7,169 unique sequences. Mature chains of
      163 different toxin-like polypeptides were predicted on the basis of well
      established methodology. The number of protein precursors of these polypeptides
      was appreciably numerous than the number of mature polypeptides. A total of 451
      different polypeptide precursors, translated from 795 unique nucleotide
      sequences, were deduced. A homology search divided the 163 mature polypeptide
      sequences into 16 superfamilies and 19 singletons. The number of mature toxins in
      a superfamily ranged from 2 to 49, whereas the diversity of the original
      nucleotide sequences was greater (2-261 variants). We observed a predominance of
      inhibitor cysteine knot toxin-like polypeptides among the cysteine-containing
      structures in the analyzed transcriptome bank. Uncommon spatial folds were also
      found. 

PMID- 25977781
TI  - A draft genome for the African crocodilian trypanosome Trypanosoma grayi.
AB  - The availability of genome sequence data has greatly enhanced our understanding
      of the adaptations of trypanosomatid parasites to their respective host
      environments. However, these studies remain somewhat restricted by modest taxon
      sampling, generally due to focus on the most important pathogens of humans. To
      address this problem, at least in part, we are releasing a draft genome sequence
      for the African crocodilian trypanosome, Trypanosoma grayi ANR4. This dataset
      comprises genomic DNA sequences assembled de novo into contigs, encompassing over
      10,000 annotated putative open reading frames and predicted protein products.
      Using phylogenomic approaches we demonstrate that T. grayi is more closely
      related to Trypanosoma cruzi than it is to the African trypanosomes T. brucei, T.
      congolense and T. vivax, despite the fact T. grayi and the African trypanosomes
      are each transmitted by tsetse flies. The data are deposited in publicly
      accessible repositories where we hope they will prove useful to the community in
      evolutionary studies of the trypanosomatids. 

PMID- 25977782
TI  - Longitudinal recordings of the vocalizations of immature Gombe chimpanzees for
      developmental studies.
AB  - Many researchers are interested in chimpanzee vocal communication, both as an
      important aspect of chimpanzee social behavior and as a source of insights into
      the evolution of human language. Nonetheless, very little is known about how
      chimpanzee vocal communication develops from infancy to adulthood. The largest
      dataset of audiorecordings from free-living immature chimpanzees was collected by
      the late Hetty van de Rijt-Plooij and Frans X. Plooij at Gombe National Park,
      Tanzania (1971-1973). These recordings have not yet been analysed. Therefore, the
      most extensive effort to study the development of chimpanzee vocalizations
      remains unfinished. The audiospecimens total over 10 h on 28 tapes, including 20
      tapes focusing on 17 specific immature individuals with a total of 1,136
      recordings. In order to make this dataset available to more researchers, the
      analogue sound recordings were digitized and stored in the Macaulay Library and
      the Dryad Repository. In addition, the original notes on the contexts of the
      calls were translated and transcribed from Dutch into English. 

PMID- 25977783
TI  - An extended Arctic proxy temperature database for the past 2,000 years.
AB  - Robust climate reconstructions of the most recent centuries and millennia are
      invaluable for placing modern warming in the context of natural variability. Here
      we present an extended and revised database (version 1.1) of proxy temperature
      records recently used to reconstruct Arctic temperatures for the past 2,000
      years. The datasets are presented in a machine-readable format, and have been
      extended with the geochronologic data and consistently generated time-uncertain
      ensembles, which will be useful in future analyses of the influence of
      geochronologic uncertainty. A standardized description of the seasonality of the
      temperature response for each record, as reported by the original authors, is
      also included to motivate a more nuanced approach to integrating records with
      variable seasonal sensitivities. Despite the predominance of seasonal, rather
      than annual, temperature responders in the database, comparisons with the
      instrumental record of temperature suggest that, as a whole, the datasets best
      record annual temperature variability across the Arctic, especially in northeast
      Canada and Greenland, where the density of records is highest. 

PMID- 25977784
TI  - Artificial selection on anther exsertion in wild radish, Raphanus raphanistrum.
AB  - To study the genetic architecture of anther exsertion, a trait under stabilizing
      selection in wild radish, artificial selection on anther exsertion was applied
      for 11 generations. Two replicate lines each of increased and decreased exsertion
      plus two randomly-mated controls were included. Full pedigree information is
      available from generation five. To estimate correlated responses to selection,
      571 plants from all lines and matrilines were grown in the greenhouse and a
      number of floral, growth, and phenology traits were measured. To create an
      outbred F2 mapping population, all possible crosses among the two high and two
      low exsertion lines were made, using a multiple-family design to capture the
      genetic variance still present after 11 generations of selection. Six floral
      traits were measured on 40 parents, 240 F1, and 4,868 F2 offspring. Opportunities
      for reuse of these data include traits not previously analyzed, other analyses,
      especially using the pedigree and fitness data, and seeds from all generations
      and photos of flowers in the later generations are available. 

PMID- 25977785
TI  - A Southern Indian Ocean database of hydrographic profiles obtained with
      instrumented elephant seals.
AB  - The instrumentation of southern elephant seals with satellite-linked CTD tags has
      offered unique temporal and spatial coverage of the Southern Indian Ocean since
      2004. This includes extensive data from the Antarctic continental slope and shelf
      regions during the winter months, which is outside the conventional areas of Argo
      autonomous floats and ship-based studies. This landmark dataset of around 75,000
      temperature and salinity profiles from 20-140  degrees E, concentrated on the
      sector between the Kerguelen Islands and Prydz Bay, continues to grow through the
      coordinated efforts of French and Australian marine research teams. The seal data
      are quality controlled and calibrated using delayed-mode techniques involving
      comparisons with other existing profiles as well as cross-comparisons similar to
      established protocols within the Argo community, with a resulting accuracy of +/
      0.03  degrees C in temperature and +/-0.05 in salinity or better. The data offer
      invaluable new insights into the water masses, oceanographic processes and
      provides a vital tool for oceanographers seeking to advance our understanding of
      this key component of the global ocean climate. 

PMID- 25977786
TI  - Metabolic differences in ripening of Solanum lycopersicum 'Ailsa Craig' and three
      monogenic mutants.
AB  - Application of mass spectrometry enables the detection of metabolic differences
      between groups of related organisms. Differences in the metabolic fingerprints of
      wild-type Solanum lycopersicum and three monogenic mutants, ripening inhibitor
      (rin), non-ripening (nor) and Colourless non-ripening (Cnr), of tomato are
      captured with regard to ripening behaviour. A high-resolution tandem mass
      spectrometry system coupled to liquid chromatography produced a time series of
      the ripening behaviour at discrete intervals with a focus on changes post
      anthesis. Internal standards and quality controls were used to ensure system
      stability. The raw data of the samples and reference compounds including study
      protocols have been deposited in the open metabolomics database MetaboLights via
      the metadata annotation tool Isatab to enable efficient re-use of the datasets,
      such as in metabolomics cross-study comparisons or data fusion exercises. 

PMID- 25977787
TI  - Open data for evolutionary synthesis: an introduction to the NESCent collection.

PMID- 25977788
TI  - A repository of assays to quantify 10,000 human proteins by SWATH-MS.
AB  - Mass spectrometry is the method of choice for deep and reliable exploration of
      the (human) proteome. Targeted mass spectrometry reliably detects and quantifies
      pre-determined sets of proteins in a complex biological matrix and is used in
      studies that rely on the quantitatively accurate and reproducible measurement of
      proteins across multiple samples. It requires the one-time, a priori generation
      of a specific measurement assay for each targeted protein. SWATH-MS is a mass
      spectrometric method that combines data-independent acquisition (DIA) and
      targeted data analysis and vastly extends the throughput of proteins that can be
      targeted in a sample compared to selected reaction monitoring (SRM). Here we
      present a compendium of highly specific assays covering more than 10,000 human
      proteins and enabling their targeted analysis in SWATH-MS datasets acquired from
      research or clinical specimens. This resource supports the confident detection
      and quantification of 50.9% of all human proteins annotated by UniProtKB/Swiss
      Prot and is therefore expected to find wide application in basic and clinical
      research. Data are available via ProteomeXchange (PXD000953-954) and SWATHAtlas
      (SAL00016-35). 

PMID- 25977789
TI  - Building the graph of medicine from millions of clinical narratives.
AB  - Electronic health records (EHR) represent a rich and relatively untapped resource
      for characterizing the true nature of clinical practice and for quantifying the
      degree of inter-relatedness of medical entities such as drugs, diseases,
      procedures and devices. We provide a unique set of co-occurrence matrices,
      quantifying the pairwise mentions of 3 million terms mapped onto 1 million
      clinical concepts, calculated from the raw text of 20 million clinical notes
      spanning 19 years of data. Co-frequencies were computed by means of a
      parallelized annotation, hashing, and counting pipeline that was applied over
      clinical notes from Stanford Hospitals and Clinics. The co-occurrence matrix
      quantifies the relatedness among medical concepts which can serve as the basis
      for many statistical tests, and can be used to directly compute Bayesian
      conditional probabilities, association rules, as well as a range of test
      statistics such as relative risks and odds ratios. This dataset can be leveraged
      to quantitatively assess comorbidity, drug-drug, and drug-disease patterns for a
      range of clinical, epidemiological, and financial applications. 

PMID- 25977791
TI  - Genomes of diverse isolates of the marine cyanobacterium Prochlorococcus.
AB  - The marine cyanobacterium Prochlorococcus is the numerically dominant
      photosynthetic organism in the oligotrophic oceans, and a model system in marine
      microbial ecology. Here we report 27 new whole genome sequences (2 complete and
      closed; 25 of draft quality) of cultured isolates, representing five major
      phylogenetic clades of Prochlorococcus. The sequenced strains were isolated from
      diverse regions of the oceans, facilitating studies of the drivers of microbial
      diversity-both in the lab and in the field. To improve the utility of these
      genomes for comparative genomics, we also define pre-computed clusters of
      orthologous groups of proteins (COGs), indicating how genes are distributed among
      these and other publicly available Prochlorococcus genomes. These data represent
      a significant expansion of Prochlorococcus reference genomes that are useful for
      numerous applications in microbial ecology, evolution and oceanography. 

PMID- 25977793
TI  - DNA methylation temporal profiling following peripheral versus central nervous
      system axotomy.
AB  - The regulatory mechanisms responsible for the gene expression pattern associated
      with axotomy-dependent signaling affecting the neuronal phenotype, including the
      axonal regenerative program, remain unclear. To further this understanding, we
      recently performed DNA methylation temporal profiling in lumbar dorsal root
      ganglia (DRG) after axotomy of the central spinal (non-regenerating) and of the
      peripheral sciatic nerve (regenerating) axonal branches. DNA methylation
      microarrays for mouse gene promoters and CpG islands (Roche/NimbleGen) were
      employed after immunoprecipitation of 5-methylcytosine-DNA. Here we provide a
      detailed data descriptor of this DNA methylation dataset, which allows in depth
      evaluation of the experimental design, assessment of data reproducibility and a
      full interactive operator-based systematic data analysis. In fact, we offer a
      methylation 'hit' scoring map of the whole microarray data in a workable
      spreadsheet that allows data sorting by genes, conditions or hits of interests
      that is ready for functional gene annotation and classification. This dataset
      allows investigators bioinformatic comparison to other epigenetic and gene
      expression datasets and further experimental characterization of the role of DNA
      methylation in axotomy-dependent pathways. 

PMID- 25977792
TI  - Reliability of brain volume measurements: a test-retest dataset.
AB  - Evaluation of neurodegenerative disease progression may be assisted by
      quantification of the volume of structures in the human brain using magnetic
      resonance imaging (MRI). Automated segmentation software has improved the
      feasibility of this approach, but often the reliability of measurements is
      uncertain. We have established a unique dataset to assess the repeatability of
      brain segmentation and analysis methods. We acquired 120 T1-weighted volumes from
      3 subjects (40 volumes/subject) in 20 sessions spanning 31 days, using the
      protocol recommended by the Alzheimer's Disease Neuroimaging Initiative (ADNI).
      Each subject was scanned twice within each session, with repositioning between
      the two scans, allowing determination of test-retest reliability both within a
      single session (intra-session) and from day to day (inter-session). To
      demonstrate the application of the dataset, all 3D volumes were processed using
      FreeSurfer v5.1. The coefficient of variation of volumetric measurements was
      between 1.6% (caudate) and 6.1% (thalamus). Inter-session variability exceeded
      intra-session variability for lateral ventricle volume (P<0.0001), indicating
      that ventricle volume in the subjects varied between days. 

PMID- 25977790
TI  - A comprehensive collection of systems biology data characterizing the host
      response to viral infection.
AB  - The Systems Biology for Infectious Diseases Research program was established by
      the U.S. National Institute of Allergy and Infectious Diseases to investigate
      host-pathogen interactions at a systems level. This program generated 47
      transcriptomic and proteomic datasets from 30 studies that investigate in vivo
      and in vitro host responses to viral infections. Human pathogens in the
      Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian
      H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS
      CoV), were investigated. Study validation was demonstrated via experimental
      quality control measures and meta-analysis of independent experiments performed
      under similar conditions. Primary assay results are archived at the GEO and
      PeptideAtlas public repositories, while processed statistical results together
      with standardized metadata are publically available at the Influenza Research
      Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By
      comparing data from mutant versus wild-type virus and host strains, RNA versus
      protein differential expression, and infection with genetically similar strains,
      these data can be used to further investigate genetic and physiological
      determinants of host responses to viral infection. 

PMID- 25977795
TI  - Scrutinizing the datasets obtained from nanoscale features of spider silk fibres.
AB  - Spider silk fibres share unprecedented structural and mechanical properties which
      span from the macroscale to nanoscale and beyond. This is possible due to the
      molecular features of modular proteins termed spidroins. Thus, the investigation
      of the organizational scaffolds observed for spidroins in spider silk fibres is
      of paramount importance for reverse bioengineering. This dataset consists in
      describing a rational screening procedure to identify the nanoscale features of
      spider silk fibres. Using atomic force microscopy operated in multiple
      acquisition modes, we evaluated silk fibres from nine spider species. Here we
      present the complete results of the analyses and decrypted a number of novel
      features that could even rank the silk fibres according to desired
      mechanostructural features. This dataset will allow other researchers to select
      the most appropriate models for synthetic biology and also lead to better
      understanding of spider silk fibres extraordinary performance that is comparable
      to the best manmade materials. 

PMID- 25977794
TI  - Flow-dependent regulation of genome-wide mRNA and microRNA expression in
      endothelial cells in vivo.
AB  - Atherosclerosis preferentially occurs in arterial regions exposed to disturbed
      blood flow (d-flow), in part, due to alterations in gene expression in the
      endothelium. While numerous in vitro studies have shown how anti-atherogenic flow
      and pro-atherogenic flow differently regulate gene expression of cultured
      endothelial cells, similar in vivo studies have been scarce. Recently, we
      developed a mouse model of atherosclerosis that rapidly develops robust
      atherosclerosis by partially ligating the left carotid artery (LCA) branches,
      while using the contralateral right carotid (RCA) as control. We also developed a
      novel method to collect endothelial-enriched RNAs from the carotids of these
      animals, which enabled us to perform genome-wide expression analyses of mRNAs and
      miRNAs in the arterial endothelium exposed to either d-flow or s-flow. These
      microarray results were used to identify novel mechanosensitive genes such as DNA
      methyltransferase-1 and miR-712 that play key roles in atherosclerosis. Here, we
      report these endothelial mRNA and miRNA expression profiles with in-depth
      information on experimental procedures along with an example of usage of these
      data. 

PMID- 25977796
TI  - Long-read, whole-genome shotgun sequence data for five model organisms.
AB  - Single molecule, real-time (SMRT) sequencing from Pacific Biosciences is
      increasingly used in many areas of biological research including de novo genome
      assembly, structural-variant identification, haplotype phasing, mRNA isoform
      discovery, and base-modification analyses. High-quality, public datasets of SMRT
      sequences can spur development of analytic tools that can accommodate unique
      characteristics of SMRT data (long read lengths, lack of GC or amplification
      bias, and a random error profile leading to high consensus accuracy). In this
      paper, we describe eight high-coverage SMRT sequence datasets from five organisms
      (Escherichia coli, Saccharomyces cerevisiae, Neurospora crassa, Arabidopsis
      thaliana, and Drosophila melanogaster) that have been publicly released to the
      general scientific community (NCBI Sequence Read Archive ID SRP040522). Data were
      generated using two sequencing chemistries (P4C2 and P5C3) on the PacBio RS II
      instrument. The datasets reported here can be used without restriction by the
      research community to generate whole-genome assemblies, test new algorithms,
      investigate genome structure and evolution, and identify base modifications in
      some of the most widely-studied model systems in biological research. 

PMID- 25977798
TI  - Multi-channel EEG recordings during 3,936 grasp and lift trials with varying
      weight and friction.
AB  - WAY-EEG-GAL is a dataset designed to allow critical tests of techniques to decode
      sensation, intention, and action from scalp EEG recordings in humans who perform
      a grasp-and-lift task. Twelve participants performed lifting series in which the
      object's weight (165, 330, or 660 g), surface friction (sandpaper, suede, or silk
      surface), or both, were changed unpredictably between trials, thus enforcing
      changes in fingertip force coordination. In each of a total of 3,936 trials, the
      participant was cued to reach for the object, grasp it with the thumb and index
      finger, lift it and hold it for a couple of seconds, put it back on the support
      surface, release it, and, lastly, to return the hand to a designated rest
      position. We recorded EEG (32 channels), EMG (five arm and hand muscles), the 3D
      position of both the hand and object, and force/torque at both contact plates.
      For each trial we provide 16 event times (e.g., 'object lift-off') and 18
      measures that characterize the behaviour (e.g., 'peak grip force'). 

PMID- 25977799
TI  - Concentrations and ratios of particulate organic carbon, nitrogen, and phosphorus
      in the global ocean.
AB  - Knowledge of concentrations and elemental ratios of suspended particles are
      important for understanding many biogeochemical processes in the ocean. These
      include patterns of phytoplankton nutrient limitation as well as linkages between
      the cycles of carbon and nitrogen or phosphorus. To further enable studies of
      ocean biogeochemistry, we here present a global dataset consisting of 100,605
      total measurements of particulate organic carbon, nitrogen, or phosphorus
      analyzed as part of 70 cruises or time-series. The data are globally distributed
      and represent all major ocean regions as well as different depths in the water
      column. The global median C:P, N:P, and C:N ratios are 163, 22, and 6.6,
      respectively, but the data also includes extensive variation between samples from
      different regions. Thus, this compilation will hopefully assist in a wide range
      of future studies of ocean elemental ratios. 

PMID- 25977797
TI  - Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex
      with array tomography.
AB  - A major question in neuroscience is how diverse subsets of synaptic connections
      in neural circuits are affected by experience dependent plasticity to form the
      basis for behavioral learning and memory. Differences in protein expression
      patterns at individual synapses could constitute a key to understanding both
      synaptic diversity and the effects of plasticity at different synapse
      populations. Our approach to this question leverages the immunohistochemical
      multiplexing capability of array tomography (ATomo) and the columnar organization
      of mouse barrel cortex to create a dataset comprising high resolution volumetric
      images of spared and deprived cortical whisker barrels stained for over a dozen
      synaptic molecules each. These dataset has been made available through the Open
      Connectome Project for interactive online viewing, and may also be downloaded for
      offline analysis using web, Matlab, and other interfaces. 

PMID- 25977801
TI  - Multi-modal ultra-high resolution structural 7-Tesla MRI data repository.
AB  - Structural brain data is key for the understanding of brain function and
      networks, i.e., connectomics. Here we present data sets available from the
      'atlasing of the basal ganglia (ATAG)' project, which provides ultra-high
      resolution 7 Tesla (T) magnetic resonance imaging (MRI) scans from young, middle
      aged, and elderly participants. The ATAG data set includes whole-brain and
      reduced field-of-view MP2RAGE and T2*-weighted scans of the subcortex and
      brainstem with ultra-high resolution at a sub-millimeter scale. The data can be
      used to develop new algorithms that help building high-resolution atlases both
      relevant for the basic and clinical neurosciences. Importantly, the present data
      repository may also be used to inform the exact positioning of electrodes used
      for deep-brain-stimulation in patients with Parkinson's disease and
      neuropsychiatric diseases. 

PMID- 25977802
TI  - Assessment of lipidomic species in hepatocyte lipid droplets from stressed mouse
      models.
AB  - Lipid droplets are considered to be the hub for storage and metabolism of
      cellular lipids. In previous work we have phenotyped the lipidome of murine
      hepatocyte lipid droplets using liquid chromatography-mass spectrometry (UHPLC
      MS) plus integrated MS/MS, followed by automatic analysis of the MS data. The
      organelles were isolated after intervention studies involving nutritional stress
      (extended feeding of a high fat diet or short term fasting), genetic stress due
      to knock-out of adipocyte triglyceride lipase, or by combined application of
      nutritional and genetic stress together ('super stress'). Lipidomics at the level
      of lipid species (profiling of lipid classes) and lipid molecular species
      (structural analysis in parallel) has unraveled clear lipid droplet phenotypes as
      judged by patterns seen best in triacylglycerol (TG) lipidomes, but also in
      diacylglycerol and phosphatidylcholine lipidomes. The combined view of these data
      presented here validates the methods used and provides high quality lipidomic
      data for further bioinformatic inspections. Examples are given for identification
      of TG species subsets considered surrogates for whole TG lipidomes. 

PMID- 25977803
TI  - A reanalysis dataset of the South China Sea.
AB  - Ocean reanalysis provides a temporally continuous and spatially gridded four
      dimensional estimate of the ocean state for a better understanding of the ocean
      dynamics and its spatial/temporal variability. Here we present a 19-year (1992
      2010) high-resolution ocean reanalysis dataset of the upper ocean in the South
      China Sea (SCS) produced from an ocean data assimilation system. A wide variety
      of observations, including in-situ temperature/salinity profiles, ship-measured
      and satellite-derived sea surface temperatures, and sea surface height anomalies
      from satellite altimetry, are assimilated into the outputs of an ocean general
      circulation model using a multi-scale incremental three-dimensional variational
      data assimilation scheme, yielding a daily high-resolution reanalysis dataset of
      the SCS. Comparisons between the reanalysis and independent observations support
      the reliability of the dataset. The presented dataset provides the research
      community of the SCS an important data source for studying the thermodynamic
      processes of the ocean circulation and meso-scale features in the SCS, including
      their spatial and temporal variability. 

PMID- 25977800
TI  - An open science resource for establishing reliability and reproducibility in
      functional connectomics.
AB  - Efforts to identify meaningful functional imaging-based biomarkers are limited by
      the ability to reliably characterize inter-individual differences in human brain
      function. Although a growing number of connectomics-based measures are reported
      to have moderate to high test-retest reliability, the variability in data
      acquisition, experimental designs, and analytic methods precludes the ability to
      generalize results. The Consortium for Reliability and Reproducibility (CoRR) is
      working to address this challenge and establish test-retest reliability as a
      minimum standard for methods development in functional connectomics.
      Specifically, CoRR has aggregated 1,629 typical individuals' resting state fMRI
      (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly
      sharing them via the International Data-sharing Neuroimaging Initiative (INDI).
      To allow researchers to generate various estimates of reliability and
      reproducibility, a variety of data acquisition procedures and experimental
      designs are included. Similarly, to enable users to assess the impact of commonly
      encountered artifacts (for example, motion) on characterizations of inter
      individual variation, datasets of varying quality are included. 

PMID- 25977804
TI  - Electromyography data for non-invasive naturally-controlled robotic hand
      prostheses.
AB  - Recent advances in rehabilitation robotics suggest that it may be possible for
      hand-amputated subjects to recover at least a significant part of the lost hand
      functionality. The control of robotic prosthetic hands using non-invasive
      techniques is still a challenge in real life: myoelectric prostheses give limited
      control capabilities, the control is often unnatural and must be learned through
      long training times. Meanwhile, scientific literature results are promising but
      they are still far from fulfilling real-life needs. This work aims to close this
      gap by allowing worldwide research groups to develop and test movement
      recognition and force control algorithms on a benchmark scientific database. The
      database is targeted at studying the relationship between surface
      electromyography, hand kinematics and hand forces, with the final goal of
      developing non-invasive, naturally controlled, robotic hand prostheses. The
      validation section verifies that the data are similar to data acquired in real
      life conditions, and that recognition of different hand tasks by applying state
      of-the-art signal features and machine-learning algorithms is possible. 

PMID- 25977805
TI  - A high resolution 7-Tesla resting-state fMRI test-retest dataset with cognitive
      and physiological measures.
AB  - Here we present a test-retest dataset of functional magnetic resonance imaging
      (fMRI) data acquired at rest. 22 participants were scanned during two sessions
      spaced one week apart. Each session includes two 1.5 mm isotropic whole-brain
      scans and one 0.75 mm isotropic scan of the prefrontal cortex, giving a total of
      six time-points. Additionally, the dataset includes measures of mood, sustained
      attention, blood pressure, respiration, pulse, and the content of self-generated
      thoughts (mind wandering). This data enables the investigation of sources of both
      intra- and inter-session variability not only limited to physiological changes,
      but also including alterations in cognitive and affective states, at high spatial
      resolution. The dataset is accompanied by a detailed experimental protocol and
      source code of all stimuli used. 

PMID- 25977806
TI  - The multilayer temporal network of public transport in Great Britain.
AB  - Despite the widespread availability of information concerning public transport
      coming from different sources, it is extremely hard to have a complete picture,
      in particular at a national scale. Here, we integrate timetable data obtained
      from the United Kingdom open-data program together with timetables of domestic
      flights, and obtain a comprehensive snapshot of the temporal characteristics of
      the whole UK public transport system for a week in October 2010. In order to
      focus on multi-modal aspects of the system, we use a coarse graining procedure
      and define explicitly the coupling between different transport modes such as
      connections at airports, ferry docks, rail, metro, coach and bus stations. The
      resulting weighted, directed, temporal and multilayer network is provided in
      simple, commonly used formats, ensuring easy access and the possibility of a
      straightforward use of old or specifically developed methods on this new and
      extensive dataset. 

PMID- 25977807
TI  - Test-retest measurements and digital validation for in vivo neuroscience.

PMID- 25977808
TI  - A multi-subject, multi-modal human neuroimaging dataset.
AB  - We describe data acquired with multiple functional and structural neuroimaging
      modalities on the same nineteen healthy volunteers. The functional data include
      Electroencephalography (EEG), Magnetoencephalography (MEG) and functional
      Magnetic Resonance Imaging (fMRI) data, recorded while the volunteers performed
      multiple runs of hundreds of trials of a simple perceptual task on pictures of
      familiar, unfamiliar and scrambled faces during two visits to the laboratory. The
      structural data include T1-weighted MPRAGE, Multi-Echo FLASH and Diffusion
      weighted MR sequences. Though only from a small sample of volunteers, these data
      can be used to develop methods for integrating multiple modalities from multiple
      runs on multiple participants, with the aim of increasing the spatial and
      temporal resolution above that of any one modality alone. They can also be used
      to integrate measures of functional and structural connectivity, and as a
      benchmark dataset to compare results across the many neuroimaging analysis
      packages. The data are freely available from https://openfmri.org/. 

PMID- 25977809
TI  - Human olfactory receptor responses to odorants.
AB  - Although the human olfactory system is capable of discriminating a vast number of
      odors, we do not currently understand what chemical features are encoded by
      olfactory receptors. In large part this is due to a paucity of data in a search
      space covering the interactions of hundreds of receptors with billions of odorous
      molecules. Of the approximately 400 intact human odorant receptors, only 10% have
      a published ligand. Here we used a heterologous luciferase assay to screen 73
      odorants against a clone library of 511 human olfactory receptors. This dataset
      will allow other researchers to interrogate the combinatorial nature of olfactory
      coding. 

PMID- 25977811
TI  - Ctrl alt share.

PMID- 25977812
TI  - High-resolution gene expression data from blastoderm embryos of the scuttle fly
      Megaselia abdita.
AB  - Gap genes are involved in segment determination during early development in
      dipteran insects (flies, midges, and mosquitoes). We carried out a systematic
      quantitative comparative analysis of the gap gene network across different
      dipteran species. Our work provides mechanistic insights into the evolution of
      this pattern-forming network. As a central component of our project, we created a
      high-resolution quantitative spatio-temporal data set of gap and maternal co
      ordinate gene expression in the blastoderm embryo of the non-drosophilid scuttle
      fly, Megaselia abdita. Our data include expression patterns in both wild-type and
      RNAi-treated embryos. The data-covering 10 genes, 10 time points, and over 1,000
      individual embryos-consist of original embryo images, quantified expression
      profiles, extracted positions of expression boundaries, and integrated expression
      patterns, plus metadata and intermediate processing steps. These data provide a
      valuable resource for researchers interested in the comparative study of gene
      regulatory networks and pattern formation, an essential step towards a more
      quantitative and mechanistic understanding of developmental evolution. 

PMID- 25977810
TI  - The pediatric template of brain perfusion.
AB  - Magnetic resonance imaging (MRI) captures the dynamics of brain development with
      multiple modalities that quantify both structure and function. These measurements
      may yield valuable insights into the neural patterns that mark healthy maturation
      or that identify early risk for psychiatric disorder. The Pediatric Template of
      Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help
      accelerate the understanding of childhood brain development as seen through the
      lens of multiple modality neuroimaging and in relation to cognitive and
      environmental factors. The PTBP uses cross-sectional and longitudinal MRI to
      quantify cortex, white matter, resting state functional connectivity and brain
      perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18
      years of age. We describe the PTBP and show, as a demonstration of validity, that
      global summary measurements capture the trajectories that demarcate critical
      turning points in brain maturation. This novel resource will allow a more
      detailed understanding of the network-level, structural and functional landmarks
      that are obtained during normal adolescent brain development. 

PMID- 25977813
TI  - Allometry and growth of eight tree taxa in United Kingdom woodlands.
AB  - As part of a project to develop predictive ecosystem models of United Kingdom
      woodlands we have collated data from two United Kingdom woodlands - Wytham Woods
      and Alice Holt. Here we present data from 582 individual trees of eight taxa in
      the form of summary variables relating to the allometric relationships between
      trunk diameter, height, crown height, crown radius and trunk radial growth rate
      to the tree's light environment and diameter at breast height. In addition the
      raw data files containing the variables from which the summary data were
      obtained. Large sample sizes with longitudinal data spanning 22 years make these
      datasets useful for future studies concerned with the way trees change in size
      and shape over their life-span. 

PMID- 25977815
TI  - A comprehensive map of genome-wide gene regulation in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (MTB) is a pathogenic bacterium responsible for 12
      million active cases of tuberculosis (TB) worldwide. The complexity and critical
      regulatory components of MTB pathogenicity are still poorly understood despite
      extensive research efforts. In this study, we constructed the first systems-scale
      map of transcription factor (TF) binding sites and their regulatory target
      proteins in MTB. We constructed FLAG-tagged overexpression constructs for 206 TFs
      in MTB, used ChIP-seq to identify genome-wide binding events and surveyed global
      transcriptomic changes for each overexpressed TF. Here we present data for the
      most comprehensive map of MTB gene regulation to date. We also define elaborate
      quality control measures, extensive filtering steps, and the gene-level overlap
      between ChIP-seq and microarray datasets. Further, we describe the use of TF
      overexpression datasets to validate a global gene regulatory network model of MTB
      and describe an online source to explore the datasets. 

PMID- 25977814
TI  - A global database of lake surface temperatures collected by in situ and satellite
      methods from 1985-2009.
AB  - Global environmental change has influenced lake surface temperatures, a key
      driver of ecosystem structure and function. Recent studies have suggested
      significant warming of water temperatures in individual lakes across many
      different regions around the world. However, the spatial and temporal coherence
      associated with the magnitude of these trends remains unclear. Thus, a global
      data set of water temperature is required to understand and synthesize global,
      long-term trends in surface water temperatures of inland bodies of water. We
      assembled a database of summer lake surface temperatures for 291 lakes collected
      in situ and/or by satellites for the period 1985-2009. In addition, corresponding
      climatic drivers (air temperatures, solar radiation, and cloud cover) and
      geomorphometric characteristics (latitude, longitude, elevation, lake surface
      area, maximum depth, mean depth, and volume) that influence lake surface
      temperatures were compiled for each lake. This unique dataset offers an
      invaluable baseline perspective on global-scale lake thermal conditions as
      environmental change continues. 

PMID- 25977816
TI  - Sequence variants from whole genome sequencing a large group of Icelanders.
AB  - We have accumulated considerable data on the genetic makeup of the Icelandic
      population by sequencing the whole genomes of 2,636 Icelanders to depth of at
      least 10X and by chip genotyping 101,584 more. The sequencing was done with
      Illumina technology. The median sequencing depth was 20X and 909 individuals were
      sequenced to a depth of at least 30X. We found 20 million single nucleotide
      polymorphisms (SNPs) and 1.5 million insertions/deletions (indels) that passed
      stringent quality control. Almost all the common SNPs (derived allele frequency
      (DAF) over 2%) that we identified in Iceland have been observed by either dbSNP
      (build 137) or the Exome Sequencing Project (ESP) while only 60 and 20% of rare
      (DAF<0.5%) SNPs and indels in coding regions, the most heavily studied parts of
      the genome, have been observed in the public databases. Features of our variant
      data, such as the transition/transversion ratio and the length distribution of
      indels, are similar to published reports. 

PMID- 25977817
TI  - A summary of eight traits of Coleoptera, Hemiptera, Orthoptera and Araneae,
      occurring in grasslands in Germany.
AB  - Analyses of species traits have increased our understanding of how environmental
      drivers such as disturbances affect the composition of arthropod communities and
      related processes. There are, however, few studies on which traits in the
      arthropod community are affected by environmental changes and which traits affect
      ecosystem functioning. The assembly of arthropod traits of several taxa is
      difficult because of the large number of species, limited availability of trait
      databases and differences in available traits. We sampled arthropod species data
      from a total of 150 managed grassland plots in three regions of Germany. These
      plots represent the spectrum from extensively used pastures to mown pastures to
      intensively managed and fertilized meadows. In this paper, we summarize
      information on body size, dispersal ability, feeding guild and specialization
      (within herbivores), feeding mode, feeding tissue (within herbivorous suckers),
      plant part (within herbivorous chewers), endophagous lifestyle (within
      herbivores), and vertical stratum use for 1,230 species of Coleoptera, Hemiptera
      (Heteroptera, Auchenorrhyncha), Orthoptera (Saltatoria: Ensifera, Caelifera), and
      Araneae, sampled by sweep-netting between 2008 and 2012. We compiled traits from
      various literature sources and complemented data from reliable internet sources
      and the authors' experience. 

PMID- 25977818
TI  - Sequence data for Clostridium autoethanogenum using three generations of
      sequencing technologies.
AB  - During the past decade, DNA sequencing output has been mostly dominated by the
      second generation sequencing platforms which are characterized by low cost, high
      throughput and shorter read lengths for example, Illumina. The emergence and
      development of so called third generation sequencing platforms such as PacBio has
      permitted exceptionally long reads (over 20 kb) to be generated. Due to read
      length increases, algorithm improvements and hybrid assembly approaches, the
      concept of one chromosome, one contig and automated finishing of microbial
      genomes is now a realistic and achievable task for many microbial laboratories.
      In this paper, we describe high quality sequence datasets which span three
      generations of sequencing technologies, containing six types of data from four
      NGS platforms and originating from a single microorganism, Clostridium
      autoethanogenum. The dataset reported here will be useful for the scientific
      community to evaluate upcoming NGS platforms, enabling comparison of existing and
      novel bioinformatics approaches and will encourage interest in the development of
      innovative experimental and computational methods for NGS data. 

PMID- 25977819
TI  - De novo transcriptome assembly databases for the central nervous system of the
      medicinal leech.
AB  - The study of non-model organisms stands to benefit greatly from genetic and
      genomic data. For a better understanding of the molecular mechanisms driving
      neuronal development, and to characterize the entire leech Hirudo medicinalis
      central nervous system (CNS) transcriptome we combined Trinity for de-novo
      assembly and Illumina HiSeq2000 for RNA-Seq. We present a set of 73,493 de-novo
      assembled transcripts for the leech, reconstructed from RNA collected, at a
      single ganglion resolution, from the CNS. This set of transcripts greatly
      enriches the available data for the leech. Here, we share two databases, such
      that each dataset allows a different type of search for candidate homologues. The
      first is the raw set of assembled transcripts. This set allows a sequence-based
      search. A comprehensive analysis of which revealed 22,604 contigs with high e
      values, aligned versus the Swiss-Prot database. This analysis enabled the
      production of the second database, which includes correlated sequences to
      annotated transcript names, with the confidence of BLAST best hit. 

PMID- 25977820
TI  - A global compendium of human Crimean-Congo haemorrhagic fever virus occurrence.
AB  - In order to map global disease risk, a geographic database of human Crimean-Congo
      haemorrhagic fever virus (CCHFV) occurrence was produced by surveying peer
      reviewed literature and case reports, as well as informal online sources. Here we
      present this database, comprising occurrence data linked to geographic point or
      polygon locations dating from 1953 to 2013. We fully describe all data
      collection, geo-positioning, database management and quality-control procedures.
      This is the most comprehensive database of confirmed CCHF occurrence in humans to
      date, containing 1,721 geo-positioned occurrences in total. 

PMID- 25977821
TI  - Now, later of never: multicenter randomized controlled trial call--is surgery
      necessary after atypical breast core biopsy results in mammographic screening
      settings?
AB  - Breast cancer mammographic screening leads to detection of premalignant and
      preinvasive lesions with an increasing frequency. Nevertheless, current
      epidemiologic evidence indicates that the screening reduces breast cancer
      specific mortality, but not overall mortality in breast cancer patients. The
      evidence is lacking whether aggressive eradication of DCIS (preinvasive form of
      breast carcinoma) by surgery and radiation is of survival benefit, as long-term
      breast cancer specific mortality in a cohort of patients with DCIS is already in
      a single digit percent range. Furthermore, it is currently not known whether the
      aggressive surgical eradication of atypical breast lesions which fall short of
      diagnosis of DCIS is of any benefit for the patients. Here we propose a model for
      a randomized controlled trial to generate high level evidence and solve this
      dilemma. 

PMID- 25977823
TI  - Malignant perivascular epithelioid cardiac sarcomas: a case report and a review
      of the literature.
AB  - Cardiac tumors, either benign or malignant, are difficult to diagnose due to
      their rarity, variety, and nonspecific presentation. Since primary cardiac
      sarcoma remains an unusual diagnosis, the literature on its presentation,
      diagnosis, and optimal management remains scarce. To our knowledge the following
      case of cardiac perivascular epithelioid cell tumor is the fourth reported case
      found in the literature. Although complete surgical resection remains the gold
      standard for cardiac sarcomas, our case demonstrates that not all of them can be
      completely resected. 

PMID- 25977824
TI  - Wire in the heart: fracture and fragment embolization of retrievable inferior
      vena cava filter into the right ventricle.
AB  - We report a case of a 58-year-old female who was found to have a fractured limb
      of her IVC filter in her right ventricle during a cardiac catheterization. A 25
      mm radioopaque thin linear structure was seen in the proximal portion of the
      right ventricle. It was fixed and did not migrate or change position during
      investigations. On fluoroscopy, the IVC filter was observed in an appropriate
      location in the midabdomen. Yet, fractures of at least two of the metal
      filamentous legs of the IVC device were noticed. The patient was made aware of
      the many risks associated with filter removal. Due to the high risks of the
      procedure, she refused surgery and the filter fragment was not removed. We
      present this case to underscore the potential complications of IVC filters. 

PMID- 25977822
TI  - Modulation of hippocampal neural plasticity by glucose-related signaling.
AB  - Hormones and peptides involved in glucose homeostasis are emerging as important
      modulators of neural plasticity. In this regard, increasing evidence shows that
      molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1,
      and ghrelin impact on the function of the hippocampus, which is a key area for
      learning and memory. Indeed, all these factors affect fundamental hippocampal
      properties including synaptic plasticity (i.e., synapse potentiation and
      depression), structural plasticity (i.e., dynamics of dendritic spines), and
      adult neurogenesis, thus leading to modifications in cognitive performance. Here,
      we review the main mechanisms underlying the effects of glucose metabolism on
      hippocampal physiology. In particular, we discuss the role of these signals in
      the modulation of cognitive functions and their potential implications in
      dysmetabolism-related cognitive decline. 

PMID- 25977825
TI  - Donor-derived myeloid sarcoma in two kidney transplant recipients from a single
      donor.
AB  - We report the rare occurrence of donor-derived myeloid sarcoma in two kidney
      transplant patients who received organs from a single deceased donor. There was
      no evidence of preexisting hematologic malignancy in the donor at the time of
      organ recovery. Both recipients developed leukemic involvement that appeared to
      be limited to the transplanted organ. Fluorescence in situ hybridization (FISH)
      and molecular genotyping analyses confirmed that the malignant cells were of
      donor origin in each patient. Allograft nephrectomy and immediate withdrawal of
      immunosuppression were performed in both cases; systemic chemotherapy was
      subsequently administered to one patient. Both recipients were in remission at
      least one year following the diagnosis of donor-derived myeloid sarcoma. These
      cases suggest that restoration of the immune system after withdrawal of
      immunosuppressive therapy and allograft nephrectomy may be sufficient to control
      HLA-mismatched donor-derived myeloid sarcoma without systemic involvement. 

PMID- 25977826
TI  - Aggressive angiomyxoma of the vulva: a bizarre perineal lesion.
AB  - Introduction. Aggressive angiomyxoma is a rare, slowly growing, and benign tumour
      of mesenchymal origin, which affects women of reproductive age and is associated
      with a high risk of local recurrence. Case Presentation. A case of a 47-year-old
      white female is presented herein, with a large polypoid, gelatinous mass on the
      right labia majora, measuring 26 * 21 * 6 cm. Histopathologically, the lesion was
      composed of spindle and stellate-shaped cells embedded in a myxoid matrix.
      Another specific feature was the presence of variable-sized thin-walled
      capillaries and thick-walled vascular channels. The patient underwent wide local
      excision of the tumour with clear margins and developed local recurrence 18
      months later. Discussion. Aggressive angiomyxoma of the vulva needs to be
      distinguished from benign myxoid tumors with a low risk of local recurrence as
      well as from malignant myxoid neoplasms. Usually wide local excision with tumour
      free margins and occasionally hormonal manipulation is the treatment of choice. 

PMID- 25977827
TI  - Ascending tonic clonic seizure syndrome after percutaneous vertebroplasty.
AB  - Background Context. Cement leakage is not a rare complication of vertebroplasty,
      but ascending tonic clonic seizure syndrome is exceptionally rare. We herein
      report the first case to our knowledge of this complication related to
      vertebroplasty. Purpose. We herein report the first case of ascending tonic
      clonic seizure syndrome following epidural cement leakage after percutaneous
      vertebroplasty in a patient with multiple osteoporotic compression fractures.
      Study Design. CASE REPORT: Methods. A 64-year-old woman with T8, T10, L2, and L4
      osteoporotic compression fractures underwent percutaneous vertebroplasty using
      polymethylmethacrylate. 40 minutes after the procedure the patient started
      suffering back and leg pain, having repetitive myoclonic jerks lasting 15 seconds
      of the lower extremities, spasm of the back, dyspnea, sinus tachycardia,
      hypoxemia, and metabolic acidosis. Results. The patient recovered completely due
      to a combination of early effective resuscitation and considered definitive
      management. Conclusions. Percutaneous vertebroplasty with polymethylmethacrylate
      is relatively safe but has few dangerous complications, which should be prevented
      by a meticulous technique and excellent image quality.

PMID- 25977828
TI  - Adult langerhans cell histiocytosis with hepatic and pulmonary involvement.
AB  - Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of
      Langerhans cells of unknown etiology. It can involve multiple organ systems with
      different clinical presentation, which complicates the diagnosis. It can range
      from isolated to multisystem disease with different prognosis. Although common
      among children, liver involvement is relatively rare in adults and frequently
      overlooked. Natural history of liver LCH fits into two stages: an early stage
      with infiltration by histiocytes and a late stage with sclerosis of the biliary
      tree. Pulmonary findings are more common and include multiple nodules in
      different stages of cavitation, predominantly in the upper lobes. We present a
      case of adult LCH with pulmonary and biopsy proven liver involvement with
      resolution of the hepatic findings after treatment. 

PMID- 25977829
TI  - Intramucosal carcinoma of the appendix arising from traditional serrated adenoma.
AB  - Introduction. Serrated adenomas of the appendix are rare and usually found during
      appendectomy or autopsies. The preoperative diagnosis of these tumors is
      uncommon. This report describes a case of a sessile serrated adenoma located in
      the appendix diagnosed by a screening colonoscopy and successfully treated by
      laparoscopic removal. Presentation of Case. An 86-year-old woman underwent
      colonoscopy to investigate the cause of her diarrhea, weight loss, and anemia.
      During the colonoscopy, an expansive and vegetating mass of 1.5 cm in diameter
      was identified, protruding through the appendicular ostium with slightly lateral
      growth to the cecum. The patient was referred for laparoscopic surgical resection
      due to the location of the lesion, which did not allow its removal by
      colonoscopy. She underwent wedge removal of the cecum without complications and
      was discharged on the 4th postoperative day. Histopathological examination showed
      the presence of a sessile serrated adenoma with an intramucosal adenocarcinoma.
      The patient is currently well one year after surgery, without endoscopic signs of
      relapse. Conclusion. Despite serrated adenomas being a possibility rarely
      described in appendix it should be recognized and properly treated because it is
      presenting a higher risk of cancer. 

PMID- 25977831
TI  - Association Analysis of COQ2 Variant in Dementia and Essential Tremor.
AB  - Objective. COQ2 mutations have been reported in Japanese multiple system atrophy
      (MSA) patients. We examined the role of COQ2 in patients with dementia and
      essential tremor (ET), two common neurodegenerative conditions. Materials &
      Methods. A total of 2064 subjects, including 560 patients with dementia, 466
      patients with ET, and 1038 healthy controls, were included. Genotyping for the
      COQ2 V393A (T>C) was carried out. Odds ratio (OR) adjusted by age and gender,
      together with 95% confidence interval (CI), was reported by means of logistic
      regression. Results. The frequency of the polymorphic variant V393A heterozygous
      (T/C) was 2.7% in dementia, 1.1% in ET, and 2.5% in controls (OR = 0.70, 95%
      confidence interval is 0.29-1.72 for dementia, and OR = 0.47, 95% confidence
      interval is 0.17-1.31, p = 0.1217 for ET). There was no significant association
      between V393A variant with dementia and ET. Conclusion. There was no significant
      association between V393A variant with dementia and ET. COQ2 gene is unlikely to
      play a significant role in patients with dementia or ET in our population. 

PMID- 25977832
TI  - Enhancing Phenolic Contents and Antioxidant Potentials of Antidesma thwaitesianum
      by Supercritical Carbon Dioxide Extraction.
AB  - Supercritical fluid extraction (SFE) has increasingly gained attention as an
      alternative technique for extraction of natural products without leaving toxic
      residues in extracts. Antidesma thwaitesianum Muell. Arg. (Phyllanthaceae), or ma
      mao, has been reported to exhibit antioxidant health benefits due to its phenolic
      constituents. To determine whether SFE technique could impact on phenolic
      contents and associated antioxidant potentials, ripe fruits of Antidesma
      thwaitesianum (Phyllanthaceae) were extracted using supercritical carbon dioxide
      (SC-CO2) and conventional solvents (ethanol, water). The results showed that the
      SC-CO2 extract contained significantly higher yield, total phenolic, flavonoid,
      and proanthocyanidin contents than those obtained from ethanol and water. It also
      demonstrated the greatest antioxidant activities as assessed by ABTS radical
      cation decolorization, DPPH radical scavenging, and ferric reducing antioxidant
      power (FRAP) assays. Further analysis using high-performance liquid
      chromatography with diode array and mass spectrometry detectors (HPLC-DAD/MSD)
      revealed the presence of catechin as a major phenolic compound of Antidesma
      thwaitesianum (Phyllanthaceae), with the maximum amount detected in the SC-CO2
      extract. These data indicate that SFE technology improves both quantity and
      quality of Antidesma thwaitesianum fruit extract. The findings added more
      reliability of using this technique to produce high added value products from
      this medicinal plant. 

PMID- 25977830
TI  - The Role of alpha-Synuclein and LRRK2 in Tau Phosphorylation.
AB  - There is now a considerable body of experimental evidence that Parkinson's
      disease arises through physiological interaction of causative molecules, leading
      to tau pathology. In this review, we discuss the physiological role of alpha
      synuclein and LRRK2 in the abnormal phosphorylation of tau. In addition, as
      recent reports have indicated that heat shock proteins- (HSPs-) inducing drugs
      can help to ameliorate neurodegenerative diseases associated with tau pathology,
      we also discuss therapeutic strategies for PD focusing on inhibition of alpha
      synuclein- and LRRK2-associated tau phosphorylation by HSPs. 

PMID- 25977833
TI  - Capillary lactate as a tool for the triage nurse among patients with SIRS at
      emergency department presentation: a preliminary report.
AB  - BACKGROUND: The triage nurse is involved in the early identification of the most
      severe patients at emergency department (ED) presentation. However, clinical
      criteria alone may be insufficient to identify them correctly. Measurement of
      capillary lactate concentration at ED presentation may help to discriminate these
      patients. The primary objective of this study was to identify the prognostic
      value of capillary lactate concentration measured by the triage nurse among
      patients presenting to the ED. METHODS: This was a prospective observational
      study, performed in the ED of a university hospital. At ED presentation,
      capillary lactate measurement was performed by the triage nurse among patients
      presenting with a clinical criteria of systemic inflammatory response syndrome
      (SIRS). Clinical variables usually used to determine severity were collected at
      presentation. Twenty-eight-day mortality and MEDS score were recorded. RESULTS:
      One hundred seventy-six patients with clinical SIRS presented to the ED. Median
      age was 72 years, and 28-day mortality was 16%. Capillary lactate at ED
      presentation was significantly higher among 28-day non-survivors than among
      survivors (5.7 mmol.L(-1) [3.2 to 7.4] vs 2.9 mmol.L(-1) [1.9 to 5.2], p =
      0.003). A score based on mottling and capillary lactate concentration >3.6
      mmol.L(-1) was significantly associated with 28-day mortality (area under curve,
      AUC = 0.75), independently of the MEDS score (AUC = 0.79) for the prediction of
      28-day mortality (AUC global model 0.87). CONCLUSIONS: A high capillary lactate
      concentration measured by the triage nurse among patients presenting to the ED
      with clinical SIRS is associated with a high risk of death. A score calculated by
      the triage nurse, based on mottling and capillary lactate concentration, appears
      to be useful for identifying the most severe patients.

PMID- 25977835
TI  - Cystic tumors of the pancreas: Opportunities and risks.
AB  - Pancreatic cystic neoplasms (PCNs) are a high prevalence disease. It is estimated
      that about 20% of the general population is affected by PCNs. Some of those
      lesions can progress till cancer, while others behave in a benign fashion. In
      particular intraductal papillary mucinous neoplasms of the pancreas can be
      considered as the pancreatic analogon to colonic polyps. Treatment of these
      precursor lesions at an early stage can potentially reduce pancreas cancer
      mortality and introduce a new "era" of preemptive pancreatic surgery. However,
      only few of those lesions have an aggressive behavior. The accuracy of
      preoperative diagnosis, i.e., the distinction between the various PCNs is around
      60%, and the ability to predict the future outcome is also less accurate. For
      this reason, a significant number of patients are currently over-treated with an
      unnecessary, high-risk surgery. Furthermore, the majority of patients with PCN
      are on life-long follow-up with imaging modality, which has huge cost
      implications for the Health Care System for limited benefits considering that a
      significant proportion of PCNs are or behave like benign lesions. The current
      guidelines for the diagnosis and management of PCNs are more based on expert
      opinion than on evidence. For all those reasons, the management of cystic tumors
      of the pancreas remains a controversial area of pancreatology. On one hand, the
      detection of PCNs and the surgical treatment of pre-cancerous neoplasms can be
      considered a big opportunity to reduce pancreatic cancer related mortality. On
      the other hand, PCNs are associated with a considerable risk of under- or over-
      treatment of patients and incur high costs for the Health Care System. 

PMID- 25977834
TI  - Insights and limits of translational research in critical care medicine.
AB  - Experimental research has always been the cornerstone of pathophysiological and
      therapeutic advances in critical care medicine, where clinical observations and
      basic research mutually fed each other in a so-called translational approach. The
      objective of this review is to address the different aspects of translational
      research in the field of critical care medicine. We herein highlighted some
      demonstrative examples including the animal-to-human approach to study host
      pathogen interactions, the human-to-animal approach for sepsis-induced
      immunosuppression, the still restrictive human approach to study critical illness
      related neuromyopathy, and the technological developments to assess the
      microcirculatory changes in critically ill patients. These examples not only
      emphasize how translational research resulted in major improvements in the
      comprehension of the pathophysiology of severe clinical conditions and offered
      promising perspectives in critical care medicine but also point out the obstacles
      to translate such achievements into clinical practice. 

PMID- 25977837
TI  - Lessons Learned and Potentials for Improvement in CNS Drug Development: ISCTM
      Section on Designing the Right Series of Experiments.
AB  - Once a molecule has been characterized as engaging an identified target at the
      appropriate location (affinity and potency), the next step involves designing
      experiments that will determine its pharmacodynamic activities both for efficacy
      (on target) and safety-tolerability (on/off target). Two expert presentations
      focused on looking back at completed programs and two concentrated on looking
      forward at ongoing programs. Specific discussions pertain to assessment of
      pharmacologic agonists (mGluR2/3, k-opiate, peroxisome proliferator-activated
      receptor gamma) and antagonists (orexin and cannabinoid) in disorders of
      cognition, mood, and anxiety. Advanced experimental study designs using genetics
      to guide a treatment trial in Alzheimer's disease and neural target-based
      approaches as the primary outcome measure in the National Institute of Mental
      Health-sponsored Fast-Fail Trials (FAST)-Mood and Anxiety Spectrum Disorders
      (MAS) initiative for depression showcases novel methodological approaches. Of
      interest, some of these initiatives were successful, while others were not, and
      two are currently ongoing. In conclusion, methodologies that were utilized and
      are currently employed to reach a successful clinical drug trial outcome are
      appreciated, and in case of failure, approaches to reviewing programs to enable
      learning that would be helpful to future programs are brought forth. This article
      is based on proceedings from the "Designing the Right Series of Experiments"
      session, which was held during the International Society for Clinical Trials
      Meeting (ISCTM) in Philadelphia, Pennsylvania, September 30 to October 2, 2013. 

PMID- 25977836
TI  - Current therapy of pediatric Crohn's disease.
AB  - Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative
      colitis, are chronic relapsing and remitting diseases of the bowel, with an
      unknown etiology and appear to involve interaction between genetic
      susceptibility, environmental factors and the immune system. Although our
      knowledge and understanding of the pathogenesis and causes of IBD have improved
      significantly, the incidence in the pediatric population is still rising. In the
      last decade more drugs and treatment option have become available including 5
      aminosalicylate, antibiotics, corticosteroids, immunomodulators and biological
      agents. Before the use of anti-tumor necrosis factor (TNF)-alpha became available
      to patients with IBD, the risk for surgery within five years of diagnosis was
      very high, however, with anti-TNF-alpha treatment the risk of surgery has
      decreased significantly. In the pediatric population a remission in disease can
      be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has
      an important role in the improvement of nutritional status and maintained growth.
      In this review we summarize the current therapeutic treatments in CD. The
      progress in the treatment options and the development of new drugs has led to
      optimized tactics for achieving the primary clinical goals of therapy - induction
      and maintenance of remission while improving the patient's growth and overall
      well-being. 

PMID- 25977838
TI  - Taking Personalized Medicine Seriously: Biomarker Approaches in Phase IIb/III
      Studies in Major Depression and Schizophrenia.
AB  - The success rate in the development of psychopharmacological compounds is
      insufficient. Two main reasons for failure have been frequently identified: 1)
      treating the wrong patients and 2) using the wrong dose. This is potentially
      based on the known heterogeneity among patients, both on a syndromal and a
      biological level. A focus on personalized medicine through better
      characterization with biomarkers has been successful in other therapeutic areas.
      Nevertheless, obstacles toward this goal that exist are 1) the perception of a
      lack of validation, 2) the perception of an expensive and complicated enterprise,
      and 3) the perception of regulatory hurdles. The authors tackle these concerns
      and focus on the utilization of biomarkers as predictive markers for treatment
      outcome. The authors primarily cover examples from the areas of major depression
      and schizophrenia. Methodologies covered include salivary and plasma collection
      of neuroendocrine, metabolic, and inflammatory markers, which identified
      subgroups of patients in the Netherlands Study of Depression and Anxiety. A
      battery of vegetative markers, including sleep-electroencephalography parameters,
      heart rate variability, and bedside functional tests, can be utilized to
      characterize the activity of a functional system that is related to treatment
      refractoriness in depression (e.g., the renin-angiotensin-aldosterone system).
      Actigraphy and skin conductance can be utilized to classify patients with
      schizophrenia and provide objective readouts for vegetative activation as a
      functional marker of target engagement. Genetic markers, related to folate
      metabolism, or folate itself, has prognostic value for the treatment response in
      patients with schizophrenia. Already, several biomarkers are routinely collected
      in standard clinical trials (e.g., blood pressure and plasma electrolytes), and
      appear to be differentiating factors for treatment outcome. Given the
      availability of a wide variety of markers, the further development and
      integration of such markers into clinical research is both required and feasible
      in order to meet the benefit of personalized medicine. This article is based on
      proceedings from the "Taking Personalized Medicine Seriously-Biomarker Approaches
      in Phase IIb/III Studies in Major Depression and Schizophrenia" session, which
      was held during the 10th Annual Scientific Meeting of the International Society
      for Clinical Trials Meeting (ISCTM) in Washington, DC, February 18 to 20, 2014. 

PMID- 25977839
TI  - Translational and Early Phase Strategies for Treatment Development: Report of
      ISCTM Autumn 2013 Symposium.
AB  - For decades, there has been a distinct disconnect translating a compound's
      effects from basic neuroscience into clinical efficacy. This disconnect has not
      only been in terms of generating approved compounds, but also in rejecting
      targets. During the drug discovery process there are key points to be adhered to
      that would strengthen the likelihood of a compound being translated to the
      clinic. These points include 1) the importance of translational pharmacology
      whereby preclinical pharmacological data should predict clinical efficacy; 2)
      rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3)
      using exposure response modeling to predict drug efficacy during proof-of-concept
      trials; 4) designing and conducting the appropriate proof-of-concept study; and
      5) optimizing Phase II studies to set the stage for success in Phase III trials.
      These topics were covered in The International Society for CNS Clinical Trials
      and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and
      early development strategies and tools led by Drs. Potter and Feltner. This
      report comprises a review of those proceedings with a concluding summary to
      advance future clinical trials. 

PMID- 25977841
TI  - Mortality of Hospitalized Patients with Pleural Effusions.
AB  - BACKGROUND: Each year in the United States an estimated 1.5 million people
      develop pleural effusions and approximately 178,000 thoracenteses (12%) are
      performed. While it has been established that malignant effusions are associated
      with increased mortality, the association between mortality and all-cause pleural
      effusions in a medical population has not been previously evaluated. Our
      objective was to evaluate associations between 30-day and 12-month all-cause
      mortality among patients with a pleural effusion. METHODS: All patients admitted
      to the medical service at Yale-New Haven Hospital during March 2011 were screened
      for pleural effusion. Pleural effusions were documented by the attending
      radiologist and the medical record was reviewed for admitting diagnosis, severity
      of illness and whether a thoracenteses was performed. The outcomes were 30-day
      and 12-month mortality after identification of the pleural effusion. RESULTS: One
      hundred and four patients admitted to the medical service had pleural effusions
      documented by the attending radiologist. At 30-days, 15% of these patients had
      died and by 12-months mortality had increased to 32%. Eleven (10.6%) of the 104
      patients underwent a thoracenteses. Severity of illness and malignancy were
      associated with 30-day mortality. For 12-month mortality, associations were found
      with age, severity of illness, malignancy, and diagnosis of pulmonary disease.
      Although sample size precluded statistical significance with mortality, the
      hazard ratio for thoracenteses and 30-day mortality was protective, suggesting a
      possible short term survival benefit. CONCLUSIONS: In hospitalized medical
      patients with a pleural effusion, age, severity of illness and malignancy or
      pulmonary disease were associated with higher 12-month mortality. Thoracenteses
      may provide a protective effect in the first 30 days, but larger studies are
      needed to detect a short-term survival benefit. The presence of a pleural
      effusion indicates a high risk of death, with 15% of patients dying within 30
      days and 32% dead within one-year of hospital admission.

PMID- 25977840
TI  - Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer's
      Disease (AD).
AB  - Since the inception of the human microbiome project (HMP) by the US National
      Institutes of Health (NIH) in 2007 there has been a keen resurgence in our
      recognition of the human microbiome and its contribution to development,
      immunity, neurophysiology, metabolic and nutritive support to central nervous
      system (CNS) health and disease. What is not generally appreciated is that (i)
      the ~1014 microbial cells that comprise the human microbiome outnumber human host
      cells by approximately one hundred-to-one; (ii) together the microbial genes of
      the microbiome outnumber human host genes by about one hundred-and-fifty to one;
      (iii) collectively these microbes constitute the largest 'diffuse organ system'
      in the human body, more metabolically active than the liver; strongly influencing
      host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and
      neurotransmission-functions; and (iv) that these microbes actively secrete highly
      complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their
      outer membranes into their immediate environment. While secreted LPS and amyloids
      are generally quite soluble as monomers over time they form into highly insoluble
      fibrous protein aggregates that are implicated in the progressive degenerative
      neuropathology of several common, age-related disorders of the human CNS
      including Alzheimer's disease (AD). This general commentary-perspective paper
      will highlight some recent findings on microbial-derived secreted LPS and
      amyloids and the potential contribution of these neurotoxic and proinflammatory
      microbial exudates to age-related inflammatory amyloidogenesis and
      neurodegeneration, with specific reference to AD wherever possible.

PMID- 25977842
TI  - Solitary Alcohol Use in Teens Is Associated With Drinking in Response to Negative
      Affect and Predicts Alcohol Problems in Young Adulthood.
AB  - Adolescent solitary drinking may represent an informative divergence from
      normative behavior, with important implications for understanding risk for
      alcohol-use disorders later in life. Within a self-medication framework, we
      hypothesized that solitary alcohol use would be associated with drinking in
      response to negative affect and that such a pattern of drinking would predict
      alcohol problems in young adulthood. We tested these predictions in a
      longitudinal study in which we examined whether solitary drinking in adolescence
      (ages 12-18) predicted alcohol-use disorders in young adulthood (age 25) in 466
      alcohol-using teens recruited from clinical programs and 243 alcohol-using teens
      recruited from the community. Findings showed that solitary drinking was
      associated with drinking in response to negative affect during adolescence and
      predicted alcohol problems in young adulthood. Results indicate that drinking
      alone is an important type of alcohol-use behavior that increases risk for the
      escalation of alcohol use and the development of alcohol problems.

PMID- 25977844
TI  - Low-cost formation of bulk and localized polymer-derived carbon nanodomains from
      polydimethylsiloxane.
AB  - We present two simple alternative methods to form polymer-derived carbon
      nanodomains in a controlled fashion and at low cost, using custom-made chemical
      vapour deposition and selective laser ablation with a commercial CD-DVD platform.
      Both processes presented shiny and dark residual materials after the polymer
      combustion and according to micro-Raman spectroscopy of the domains, graphitic
      nanocrystals and carbon nanotubes have successfully been produced by the
      combustion of polydimethylsiloxane layers. The fabrication processes and
      characterization of the byproduct materials are reported. We demonstrate that CVD
      led to bulk production of graphitic nanocrystals and single-walled carbon
      nanotubes while direct laser ablation may be employed for the formation of
      localized fluorescent nanodots. In the latter case, graphitic nanodomains and
      multi-wall carbon nanotubes are left inside microchannels and preliminary results
      seem to indicate that laser ablation could offer a tuning control of the nature
      and optical properties of the nanodomains that are left inside micropatterns with
      on-demand geometries. These low-cost methods look particularly promising for the
      formation of carbon nanoresidues with controlled properties and in applications
      where high integration is desired. 

PMID- 25977843
TI  - Altering the Cognitive-Affective Dysfunctions of Psychopathic and Externalizing
      Offender Subtypes with Cognitive Remediation.
AB  - Cognitive remediation is a treatment approach with the potential to translate
      basic science into more specific, mechanism-based interventions by targeting
      particular cognitive skills. The present study translated understanding of two
      well-defined cognitive-emotion dysfunctions into novel deficit-matched
      interventions and evaluated whether cognitive remediation would demonstrate
      specific and generalizable change. Two antisocial-subtypes, individuals with
      psychopathy and externalizing traits, are characterized by cognitive-affective
      problems that predispose them to engage in significant substance abuse and
      criminal behavior, culminating in incarceration. Whereas individuals with
      psychopathy fail to consider important contextual information, individuals with
      externalizing traits lack the capacity to regulate affective reactions. Training
      designed to remedy these subtype-specific deficits led to improvement on both
      trained and non-trained tasks. Such findings offer promise for changing neural
      and behavioral patterns, even for what many consider to be the most recalcitrant
      treatment population, and presage a new era of translating cognitive-affective
      science into increasingly specific and effective interventions.

PMID- 25977845
TI  - Combination of surface- and interference-enhanced Raman scattering by CuS
      nanocrystals on nanopatterned Au structures.
AB  - We present the results of a Raman study of optical phonons in CuS nanocrystals
      (NCs) with a low areal density fabricated through the Langmuir-Blodgett
      technology on nanopatterned Au nanocluster arrays using a combination of surface-
      and interference-enhanced Raman scattering (SERS and IERS, respectively). Micro
      Raman spectra of one monolayer of CuS NCs deposited on a bare Si substrate reveal
      only features corresponding to crystalline Si. However, a new relatively strong
      peak occurs in the Raman spectrum of CuS NCs on Au nanocluster arrays at 474 cm(
      1). This feature is related to the optical phonon mode in CuS NCs and manifests
      the SERS effect. For CuS NCs deposited on a SiO2 layer this phonon mode is also
      observed due to the IERS effect. Its intensity changes periodically with
      increasing SiO2 layer thickness for different laser excitation lines and is
      enhanced by a factor of about 30. CuS NCs formed on Au nanocluster arrays
      fabricated on IERS substrates combine the advantages of SERS and IERS and
      demonstrate stronger SERS enhancement allowing for the observation of Raman
      signals from CuS NCs with an ultra-low areal density. 

PMID- 25977846
TI  - Statistics of work and orthogonality catastrophe in discrete level systems: an
      application to fullerene molecules and ultra-cold trapped Fermi gases.
AB  - The sudden introduction of a local impurity in a Fermi sea leads to an anomalous
      disturbance of its quantum state that represents a local quench, leaving the
      system out of equilibrium and giving rise to the Anderson orthogonality
      catastrophe. The statistics of the work done describe the energy fluctuations
      produced by the quench, providing an accurate and detailed insight into the
      fundamental physics of the process. We present here a numerical approach to the
      non-equilibrium work distribution, supported by applications to phenomena
      occurring at very diverse energy ranges. One of them is the valence electron
      shake-up induced by photo-ionization of a core state in a fullerene molecule. The
      other is the response of an ultra-cold gas of trapped fermions to an embedded two
      level atom excited by a fast pulse. Working at low thermal energies, we detect
      the primary role played by many-particle states of the perturbed system with one
      or two excited fermions. We validate our approach through the comparison with
      some photoemission data on fullerene films and previous analytical calculations
      on harmonically trapped Fermi gases. 

PMID- 25977847
TI  - Mapping of elasticity and damping in an alpha + beta titanium alloy through
      atomic force acoustic microscopy.
AB  - The distribution of elastic stiffness and damping of individual phases in an
      alpha + beta titanium alloy (Ti-6Al-4V) measured by using atomic force acoustic
      microscopy (AFAM) is reported in the present study. The real and imaginary parts
      of the contact stiffness k (*) are obtained from the contact-resonance spectra
      and by using these two quantities, the maps of local elastic stiffness and the
      damping factor are derived. The evaluation of the data is based on the mass
      distribution of the cantilever with damped flexural modes. The cantilever
      dynamics model considering damping, which was proposed recently, has been used
      for mapping of indentation modulus and damping of different phases in a metallic
      structural material. The study indicated that in a Ti-6Al-4V alloy the metastable
      beta phase has the minimum modulus and the maximum damping followed by alpha'-
      and alpha-phases. Volume fractions of the individual phases were determined by
      using a commercial material property evaluation software and were validated by
      using X-ray diffraction (XRD) and electron back-scatter diffraction (EBSD)
      studies on one of the heat-treated samples. The volume fractions of the phases
      and the modulus measured through AFAM are used to derive average modulus of the
      bulk sample which is correlated with the bulk elastic properties obtained by
      ultrasonic velocity measurements. The average modulus of the specimens estimated
      by AFAM technique is found to be within 5% of that obtained by ultrasonic
      velocity measurements. The effect of heat treatments on the ultrasonic
      attenuation in the bulk sample could also be understood based on the damping
      measurements on individual phases using AFAM. 

PMID- 25977848
TI  - Magnetic properties of self-organized Co dimer nanolines on Si/Ag(110).
AB  - We demonstrate the kinetically controlled growth of one-dimensional Co
      nanomagnets with a high lateral order on a nanopatterned Ag(110) surface. First,
      self-organized Si nanoribbons are formed upon submonolayer condensation of Si on
      the anisotropic Ag(110) surface. Depending on the growth temperature, individual
      or regular arrays (with a pitch of 2 nm) of Si nanoribbons can be grown. Next,
      the Si/Ag(110) system is used as a novel one-dimensional Si template to guide the
      growth of Co dimer nanolines on top of the Si nanoribbons, taking advantage of
      the fact that the thermally activated process of Co diffusion into the Si layer
      is efficiently hindered at 220 K. Magnetic characterization of the Co nanolines
      using X-ray magnetic circular dichroism reveals that the first atomic Co layer
      directly adsorbed onto the Si nanoribbons presents a weak magnetic response.
      However, the second Co layer exhibits an enhanced magnetization, strongly
      suggesting a ferromagnetic ordering with an in-plane easy axis of magnetization,
      which is perpendicular to the Co nanolines. 

PMID- 25977849
TI  - Microwave assisted synthesis and characterisation of a zinc oxide/tobacco mosaic
      virus hybrid material. An active hybrid semiconductor in a field-effect
      transistor device.
AB  - Tobacco mosaic virus (TMV) has been employed as a robust functional template for
      the fabrication of a TMV/zinc oxide field effect transistor (FET). A microwave
      based approach, under mild conditions was employed to synthesize stable zinc
      oxide (ZnO) nanoparticles, employing a molecular precursor. Insightful studies of
      the decomposition of the precursor were done using NMR spectroscopy and material
      characterization of the hybrid material derived from the decomposition was
      achieved using dynamic light scattering (DLS), transmission electron microscopy
      (TEM), grazing incidence X-ray diffractometry (GI-XRD) and atomic force
      microscopy (AFM). TEM and DLS data confirm the formation of crystalline ZnO
      nanoparticles tethered on top of the virus template. GI-XRD investigations
      exhibit an orientated nature of the deposited ZnO film along the c-axis. FET
      devices fabricated using the zinc oxide mineralized virus template material
      demonstrates an operational transistor performance which was achieved without any
      high-temperature post-processing steps. Moreover, a further improvement in FET
      performance was observed by adjusting an optimal layer thickness of the deposited
      ZnO on top of the TMV. Such a bio-inorganic nanocomposite semiconductor material
      accessible using a mild and straightforward microwave processing technique could
      open up new future avenues within the field of bio-electronics. 

PMID- 25977850
TI  - Applications of three-dimensional carbon nanotube networks.
AB  - In this paper, we show that it is possible to synthesize carbon-based three
      dimensional networks by adding sulfur, as growth enhancer, during the synthesis
      process. The obtained material is self-supporting and consists of curved and
      interconnected carbon nanotubes and to lesser extent of carbon fibers. Studies on
      the microstructure indicate that the assembly presents a marked variability in
      the tube external diameter and in the inner structure. We study the relationship
      between the observed microscopic properties and some potential applications. In
      particular, we show that the porous nature of the network is directly responsible
      for the hydrophobic and the lipophilic behavior. Moreover, we used a cut piece of
      the produced carbon material as working electrode in a standard electrochemical
      cell and, thus, demonstrating the capability of the system to respond to incident
      light in the visible and near-ultraviolet region and to generate a photocurrent. 

PMID- 25977851
TI  - Morphology control of zinc oxide films via polysaccharide-mediated, low
      temperature, chemical bath deposition.
AB  - In this study we present a three-step process for the low-temperature chemical
      bath deposition of crystalline ZnO films on glass substrates. The process
      consists of a seeding step followed by two chemical bath deposition steps. In the
      second step (the first of the two bath deposition steps), a natural
      polysaccharide, namely hyaluronic acid, is used to manipulate the morphology of
      the films. Previous experiments revealed a strong influence of this
      polysaccharide on the formation of zinc oxide crystallites. The present work aims
      to transfer this gained knowledge to the formation of zinc oxide films. The
      influence of hyaluronic acid and the time of its addition on the morphology of
      the resulting ZnO film were investigated. By meticulous adjustment of the
      parameters in this step, the film morphology can be tailored to provide an
      optimal growth platform for the third step (a subsequent chemical bath deposition
      step). In this step, the film is covered by a dense layer of ZnO. This optimized
      procedure leads to ZnO films with a very high electrical conductivity, opening up
      interesting possibilities for applications of such films. The films were
      characterized by means of electron microscopy, X-ray diffraction and measurements
      of the electrical conductivity. 

PMID- 25977852
TI  - Capillary and van der Waals interactions on CaF2 crystals from amplitude
      modulation AFM force reconstruction profiles under ambient conditions.
AB  - There has been much interest in the past two decades to produce experimental
      force profiles characteristic of the interaction between nanoscale objects or a
      nanoscale object and a plane. Arguably, the advent of the atomic force microscope
      AFM was instrumental in driving such efforts because, in principle, force
      profiles could be recovered directly. Nevertheless, it has taken years before
      techniques have developed enough as to recover the attractive part of the force
      with relatively low noise and without missing information on critical ranges,
      particularly under ambient conditions where capillary interactions are believed
      to dominate. Thus a systematic study of the different profiles that may arise in
      such situations is still lacking. Here we employ the surfaces of CaF2, on which
      nanoscale water films form, to report on the range and force profiles that might
      originate by dynamic capillary interactions occurring between an AFM tip and
      nanoscale water patches. Three types of force profiles were observed under
      ambient conditions. One in which the force decay resembles the well-known inverse
      square law typical of van der Waals interactions during the first 0.5-1 nm of
      decay, a second one in which the force decays almost linearly, in relatively good
      agreement with capillary force predicted by the constant chemical potential
      approximation, and a third one in which the attractive force is almost constant,
      i.e., forms a plateau, up to 3-4 nm above the surface when the formation of a
      capillary neck dominates the tip-sample interaction. 

PMID- 25977853
TI  - Stick-slip behaviour on Au(111) with adsorption of copper and sulfate.
AB  - Several transitions in the friction coefficient with increasing load are found on
      Au(111) in sulfuric acid electrolyte containing Cu ions when a monolayer (or
      submonolayer) of Cu is adsorbed. At the corresponding normal loads, a transition
      to double or multiple slips in stick-slip friction is observed. The stick length
      in this case corresponds to multiples of the lattice distance of the adsorbed
      sulfate, which is adsorbed in a ?3 * ?7 superstructure on the copper monolayer.
      Stick-slip behaviour for the copper monolayer as well as for 2/3 coverage can be
      observed at F N >= 15 nN. At this normal load, a change from a small to a large
      friction coefficient occurs. This leads to the interpretation that the tip
      penetrates the electrochemical double layer at this point. At the potential (or
      point) of zero charge (pzc), stick-slip resolution persists at all normal forces
      investigated. 

PMID- 25977854
TI  - Transformation of hydrogen titanate nanoribbons to TiO2 nanoribbons and the
      influence of the transformation strategies on the photocatalytic performance.
AB  - The influence of the reaction conditions during the transformation of hydrogen
      titanate nanoribbons to TiO2 nanoribbons on the phase composition, the
      morphology, the appearance of the nanoribbon surfaces and their optical
      properties was investigated. The transformations were performed (i) through a
      heat treatment in oxidative and reductive atmospheres in the temperature range of
      400-650  degrees C, (ii) through a hydrothermal treatment in neutral and basic
      environments at 160  degrees C, and (iii) through a microwave-assisted
      hydrothermal treatment in a neutral environment at 200  degrees C. Scanning
      electron microscopy investigations showed that the hydrothermal processing
      significantly affected the nanoribbon surfaces, which became rougher, while the
      transformations based on calcination in either oxidative or reductive atmospheres
      had no effect on the morphology or on the surface appearance of the nanoribbons.
      The transformations performed in the reductive atmosphere, an NH3(g)/Ar(g) flow,
      and in the ammonia solution led to nitrogen doping. The nitrogen content
      increased with an increasing calcination temperature, as was determined by X-ray
      photoelectron spectroscopy. According to electron paramagnetic resonance
      measurements the calcination in the reductive atmosphere also resulted in a
      partial reduction of Ti(4+) to Ti(3+). The photocatalytic performance of the
      derived TiO2 NRs was estimated on the basis of the photocatalytic oxidation of
      isopropanol. After calcinating in air, the photocatalytic performance of the
      investigated TiO2 NRs increased with an increased content of anatase. In
      contrast, the photocatalytic performance of the N-doped TiO2 NRs showed no
      dependence on the calcination temperature. An additional comparison showed that
      the N-doping significantly suppressed the photocatalytic performance of the TiO2
      NRs, i.e., by 3 to almost 10 times, in comparison with the TiO2 NRs derived by
      calcination in air. On the other hand, the photocatalytic performance of the
      hydrothermally derived TiO2 NRs was additionally improved by a subsequent heat
      treatment in air. 

PMID- 25977855
TI  - Stiffness of sphere-plate contacts at MHz frequencies: dependence on normal load,
      oscillation amplitude, and ambient medium.
AB  - The stiffness of micron-sized sphere-plate contacts was studied by employing high
      frequency, tangential excitation of variable amplitude (0-20 nm). The contacts
      were established between glass spheres and the surface of a quartz crystal
      microbalance (QCM), where the resonator surface had been coated with either
      sputtered SiO2 or a spin-cast layer of poly(methyl methacrylate) (PMMA). The
      results from experiments undertaken in the dry state and in water are compared.
      Building on the shifts in the resonance frequency and resonance bandwidth, the
      instrument determines the real and the imaginary part of the contact stiffness,
      where the imaginary part quantifies dissipative processes. The method is closely
      analogous to related procedures in AFM-based metrology. The real part of the
      contact stiffness as a function of normal load can be fitted with the Johnson
      Kendall-Roberts (JKR) model. The contact stiffness was found to increase in the
      presence of liquid water. This finding is tentatively explained by the rocking
      motion of the spheres, which couples to a squeeze flow of the water close to the
      contact. The loss tangent of the contact stiffness is on the order of 0.1, where
      the energy losses are associated with interfacial processes. At high amplitudes
      partial slip was found to occur. The apparent contact stiffness at large
      amplitude depends linearly on the amplitude, as predicted by the Cattaneo-Mindlin
      model. This finding is remarkable insofar, as the Cattaneo-Mindlin model assumes
      Coulomb friction inside the sliding region. Coulomb friction is typically viewed
      as a macroscopic concept, related to surface roughness. An alternative model
      (formulated by Savkoor), which assumes a constant frictional stress in the
      sliding zone independent of the normal pressure, is inconsistent with the
      experimental data. The apparent friction coefficients slightly increase with
      normal force, which can be explained by nanoroughness. In other words, contact
      splitting (i.e., a transport of shear stress across many small contacts, rather
      than a few large ones) can be exploited to reduce partial slip. 

PMID- 25977857
TI  - Structure and mechanism of the formation of core-shell nanoparticles obtained
      through a one-step gas-phase synthesis by electron beam evaporation.
AB  - The structure of core-shell Cu@silica and Ag@Si nanoparticles obtained in one
      step through evaporation of elemental precursors by a high-powered electron beam
      are investigated. The structure of the core and shell of the particles are
      investigated in order to elucidate their mechanisms of formation and factors
      affecting the synthesis. It is proposed that the formation of Cu@silica particles
      is mainly driven by surface tension differences between Cu and Si while the
      formation of Ag@Si particles is mainly driven by differences in the vapour
      concentration of the two components. 

PMID- 25977858
TI  - A simple approach to the synthesis of Cu1.8S dendrites with thiamine
      hydrochloride as a sulfur source and structure-directing agent.
AB  - A facile, green and environmental-friendly method for preparing Cu1.8S dendrites
      was developed. Copper nitrate and thiamine hydrochloride were selected as the
      starting materials in the water phase under hydrothermal conditions. No addition
      of a surfactant or a complex reagent was required for the synthesis of the Cu1.8S
      dendrite structures. Thiamine hydrochloride was employed as a sulfur source and
      structure-directing agent. The growth mechanism of Cu1.8S is tentatively
      discussed based on the experimental and computational results. 

PMID- 25977856
TI  - Protein corona - from molecular adsorption to physiological complexity.
AB  - In biological environments, nanoparticles are enshrouded by a layer of
      biomolecules, predominantly proteins, mediating its subsequent interactions with
      cells. Detecting this protein corona, understanding its formation with regards to
      nanoparticle (NP) and protein properties, and elucidating its biological
      implications were central aims of bio-related nano-research throughout the past
      years. Here, we discuss the mechanistic parameters that are involved in the
      protein corona formation and the consequences of this corona formation for both,
      the particle, and the protein. We review consequences of corona formation for
      colloidal stability and discuss the role of functional groups and NP surface
      functionalities in shaping NP-protein interactions. We also elaborate the recent
      advances demonstrating the strong involvement of Coulomb-type interactions
      between NPs and charged patches on the protein surface. Moreover, we discuss
      novel aspects related to the complexity of the protein corona forming under
      physiological conditions in full serum. Specifically, we address the relation
      between particle size and corona composition and the latest findings that help to
      shed light on temporal evolution of the full serum corona for the first time.
      Finally, we discuss the most recent advances regarding the molecular-scale
      mechanistic role of the protein corona in cellular uptake of NPs. 

PMID- 25977859
TI  - Experimental determination of the light-trapping-induced absorption enhancement
      factor in DSSC photoanodes.
AB  - For dye-sensitized solar cells (DSSC), the fundamental process that determines
      the maximum short-circuit current is the absorption of light. In such devices,
      this is produced by the concurrent phenomena of light absorption by dye molecules
      and light trapping in the mesoporous, titania photoanode structure. The
      decoupling of these two phenomena is important for device characterization and
      the design of novel photoelectrode geometries with increased optical performance.
      In this paper, this task is addressed by introducing a spectral absorption
      enhancement factor as a parameter to quantify the light trapping effect. The
      experimental value of this parameter was obtained by comparing the experimentally
      determined fraction of absorbed light by a dye-sensitized photoanode with the
      light absorbed by the dye without the mesoporous titania structure. In order to
      gain more insight from this result, the fraction of light absorbed in the
      photoanode (on the basis of the dye loading capacity of the titania nanospheres)
      was also calculated by an optical model for the two extreme cases of the absence
      of light trapping and maximum light trapping. Accordingly, the photocurrent was
      calculated under the assumption of solar irradiation, which defined two useful
      boundaries. Using the experimentally derived values of the spectral absorption
      enhancement factor in the photoanode optical model, the DSSC short-circuit
      current can be calculated with good agreement with the value measured in
      practical devices based on the same photoanode structures. Therefore, our
      approach provides a realistic description of a practical device and can be
      exploited as an useful tool to assess the optical functionality of novel
      photoanode structures. 

PMID- 25977860
TI  - Nanostructuring of GeTiO amorphous films by pulsed laser irradiation.
AB  - Laser pulse processing of surfaces and thin films is a useful tool for amorphous
      thin films crystallization, surface nanostructuring, phase transformation and
      modification of physical properties of thin films. Here we show the effects of
      nanostructuring produced at the surface and under the surface of amorphous GeTiO
      films through laser pulses using fluences of 10-30 mJ/cm(2). The GeTiO films were
      obtained by RF magnetron sputtering with 50:50 initial atomic ratio of Ge:TiO2.
      Laser irradiation was performed by using the fourth harmonic (266 nm) of a Nd:YAG
      laser. The laser-induced nanostructuring results in two effects, the first one is
      the appearance of a wave-like topography at the film surface, with a periodicity
      of 200 nm and the second one is the structure modification of a layer under the
      film surface, at a depth that is related to the absorption length of the laser
      radiation. The periodicity of the wave-like relief is smaller than the laser
      wavelength. In the modified layer, the Ge atoms are segregated in spherical
      amorphous nanoparticles as a result of the fast diffusion of Ge atoms in the
      amorphous GeTiO matrix. The temperature estimation of the film surface during the
      laser pulses shows a maximum of about 500  degrees C, which is much lower than
      the melting temperature of the GeTiO matrix. GeO gas is formed at laser fluences
      higher than 20 mJ/cm(2) and produces nanovoids in the laser-modified layer at the
      film surface. A glass transition at low temperatures could happen in the
      amorphous GeTiO film, which explains the formation of the wave-like topography.
      The very high Ge diffusivity during the laser pulse action, which is
      characteristic for liquids, cannot be reached in a viscous matrix. Our
      experiments show that the diffusivity of atomic and molecular species such as Ge
      and GeO is very much enhanced in the presence of the laser pulse field.
      Consequently, the fast diffusion drives the formation of amorphous Ge
      nanoparticles through the segregation of Ge atoms in the GeTiO matrix. The
      nanostructuring effects induced by the laser irradiation can be used in
      functionalizing the surface of the films. 

PMID- 25977861
TI  - Graphene on SiC(0001) inspected by dynamic atomic force microscopy at room
      temperature.
AB  - We investigated single-layer graphene on SiC(0001) by atomic force and tunneling
      current microscopy, to separate the topographic and electronic contributions from
      the overall landscape. The analysis revealed that the roughness evaluated from
      the atomic force maps is very low, in accord with theoretical simulations. We
      also observed that characteristic electron scattering effects on graphene edges
      and defects are not accompanied by any out-of-plane relaxations of carbon atoms. 

PMID- 25977862
TI  - Electron-stimulated purification of platinum nanostructures grown via focused
      electron beam induced deposition.
AB  - Platinum-carbon nanostructures deposited via electron beam induced deposition
      from MeCpPt(IV)Me3 are purified during a post-deposition electron exposure
      treatment in a localized oxygen ambient at room temperature. Time-dependent
      studies demonstrate that the process occurs from the top-down. Electron beam
      energy and current studies demonstrate that the process is controlled by a
      confluence of the electron energy loss and oxygen concentration. Furthermore, the
      experimental results are modeled as a 2nd order reaction which is dependent on
      both the electron energy loss density and the oxygen concentration. In addition
      to purification, the post-deposition electron stimulated oxygen purification
      process enhances the resolution of the EBID process due to the isotropic carbon
      removal from the as-deposited materials which produces high-fidelity shape
      retention. 

PMID- 25977863
TI  - Pt- and Pd-decorated MWCNTs for vapour and gas detection at room temperature.
AB  - Here we report on the gas sensing properties of multiwalled carbon nanotubes
      decorated with sputtered Pt or Pd nanoparticles. Sputtering allows for an oxygen
      plasma treatment that removes amorphous carbon from the surface of the carbon
      nanotubes and creates oxygenated surface defects in which metal nanoparticles
      nucleate within a few minutes. The decoration with the 2 nm Pt or the 3 nm Pd
      nanoparticles is very homogeneous. This procedure is performed at the device
      level (i.e., for carbon nanotubes deposited onto sensor substrates) for many
      devices in one batch, which illustrates the scalability for the mass production
      of affordable nanosensors. The response to selected aromatic and non-aromatic
      volatile organic compounds, as well as pollutant gases has been studied. Pt- and
      Pd-decorated multiwalled carbon nanotubes show a fully reversible response to the
      non-aromatic volatile organic compounds tested when operated at room temperature.
      In contrast, these nanomaterials were not responsive to the aromatic compounds
      studied (measured at concentrations up to 50 ppm). Therefore, these sensors could
      be useful in a small, battery-operated alarm detector, for example, which is able
      to discriminate aromatic from non-aromatic volatile organic compounds in ambient.

PMID- 25977864
TI  - Effects of swift heavy ion irradiation on structural, optical and photocatalytic
      properties of ZnO-CuO nanocomposites prepared by carbothermal evaporation method.
AB  - ZnO-CuO nanocomposite thin films were prepared by carbothermal evaporation of ZnO
      and Cu, combined with annealing. The effects of 90 MeV Ni(7+) ion irradiation on
      the structural and optical properties of ZnO-CuO nanocomposites were studied by
      using X-ray diffraction (XRD), field emission scanning electron microscopy
      (FESEM), UV-visible absorption spectroscopy and Raman spectroscopy. XRD studies
      showed the presence of ZnO and CuO nanostructures in the nanocomposites. FESEM
      images revealed the presence of nanosheets and nanorods in the nanocomposites.
      The photocatalytic activity of ZnO-CuO nanocomposites was evaluated on the basis
      of degradation of methylene blue (MB) and methyl orange (MO) dyes under sun light
      irradiation and it was observed that swift heavy ion irradiation results in
      significant enhancement in the photocatalytic efficiency of ZnO-CuO
      nanocomposites towards degradation of MB and MO dyes. The possible mechanism for
      the enhanced photocatalytic activity of ZnO-CuO nanocomposites is proposed. We
      attribute the observed enhanced photocatalytic activity of ZnO-CuO nanocomposites
      to the combined effects of improved sun light utilization and suppression of the
      recombination of photogenerated charge carriers in ZnO-CuO nanocomposites. 

PMID- 25977865
TI  - Simulation tool for assessing the release and environmental distribution of
      nanomaterials.
AB  - An integrated simulation tool was developed for assessing the potential release
      and environmental distribution of nanomaterials (RedNano) based on a life cycle
      assessment approach and multimedia compartmental modeling coupled with
      mechanistic intermedia transport processes. The RedNano simulation tool and its
      web-based software implementation enables rapid "what-if?" scenario analysis, in
      order to assess the response of an environmental system to various release
      scenarios of engineered nanomaterials (ENMs). It also allows for the
      investigation of the impact of geographical and meteorological parameters on ENM
      distribution in the environment, comparison of the impact of ENM production and
      potential releases on different regions, and estimation of source release rates
      based on monitored ENM concentrations. Moreover, the RedNano simulation tool is
      suitable for research, academic, and regulatory purposes. Specifically, it has
      been used in environmental multimedia impact assessment courses at both the
      undergraduate and graduate levels. The RedNano simulation tool can also serve as
      a decision support tool to rapidly and critically assess the potential
      environmental implications of ENMs and thus ensure that nanotechnology is
      developed in a productive and environmentally responsible manner. 

PMID- 25977866
TI  - Automatic morphological characterization of nanobubbles with a novel image
      segmentation method and its application in the study of nanobubble coalescence.
AB  - Nanobubbles (NBs) on hydrophobic surfaces in aqueous solvents have shown great
      potential in numerous applications. In this study, the morphological
      characterization of NBs in AFM images was carried out with the assistance of a
      novel image segmentation method. The method combines the classical threshold
      method and a modified, active contour method to achieve optimized image
      segmentation. The image segmentation results obtained with the classical
      threshold method and the proposed, modified method were compared. With the
      modified method, the diameter, contact angle, and radius of curvature were
      automatically measured for all NBs in AFM images. The influence of the selection
      of the threshold value on the segmentation result was discussed. Moreover, the
      morphological change in the NBs was studied in terms of density, covered area,
      and volume occurring during coalescence under external disturbance. 

PMID- 25977867
TI  - Observing the morphology of single-layered embedded silicon nanocrystals by using
      temperature-stable TEM membranes.
AB  - We use high-temperature-stable silicon nitride membranes to investigate single
      layers of silicon nanocrystal ensembles by energy filtered transmission electron
      microscopy. The silicon nanocrystals are prepared from the precipitation of a
      silicon-rich oxynitride layer sandwiched between two SiO2 diffusion barriers and
      subjected to a high-temperature annealing. We find that such single layers are
      very sensitive to the annealing parameters and may lead to a significant loss of
      excess silicon. In addition, these ultrathin layers suffer from significant
      electron beam damage that needs to be minimized in order to image the pristine
      sample morphology. Finally we demonstrate how the silicon nanocrystal size
      distribution develops from a broad to a narrow log-normal distribution, when the
      initial precipitation layer thickness and stoichiometry are below a critical
      value. 

PMID- 25977868
TI  - Characterization of nanostructured ZnO thin films deposited through vacuum
      evaporation.
AB  - This work presents a novel technique to deposit ZnO thin films through a metal
      vacuum evaporation technique using colloidal nanoparticles (average size of 30
      nm), which were synthesized by our research group, as source. These thin films
      had a thickness between 45 and 123 nm as measured by profilometry. XRD patterns
      of the deposited thin films were obtained. According to the HRSEM micrographs
      worm-shaped nanostructures are observed in samples annealed at 600  degrees C and
      this characteristic disappears as the annealing temperature increases. The films
      obtained were annealed from 25 to 1000  degrees C, showing a gradual increase in
      transmittance spectra up to 85%. The optical band gaps obtained for these films
      are about 3.22 eV. The PL measurement shows an emission in the red and in the
      violet region and there is a correlation with the annealing process. 

PMID- 25977869
TI  - Fabrication of high-resolution nanostructures of complex geometry by the single
      spot nanolithography method.
AB  - The paper presents a method for the high-resolution production of polymer
      nanopatterns with controllable geometrical parameters by means of a single-spot
      electron-beam lithography technique. The essence of the method entails the
      overexposure of a positive-tone resist, spin-coated onto a substrate where
      nanoscale spots are exposed to an electron beam with a dose greater than 0.1 pC
      per dot. A single-spot enables the fabrication of a nanoring, while a chain of
      spots placed at distance of 5-30 nm from each other allows the production of a
      polymer pattern of complex geometry of sub-10 nm resolution. We demonstrate that
      in addition to the naturally oxidized silicon substrates, gold-coated substrates
      can also successfully be used for the single-spot nanopattering technique. An
      explanation of the results related to the resist overexposure was demonstrated
      using Monte Carlo simulations. Our nanofabrication method significantly
      accelerates (up to 10 times) the fabrication rate as compared to conventional
      lithography on positive-tone resist. This technique can be potentially employed
      in the electronics industry for the production of nanoprinted lithography molds,
      etching masks, nanoelectronics, nanophotonics, NEMS and MEMS devices. 

PMID- 25977870
TI  - Multiscale modeling of lithium ion batteries: thermal aspects.
AB  - The thermal behavior of lithium ion batteries has a huge impact on their lifetime
      and the initiation of degradation processes. The development of hot spots or
      large local overpotentials leading, e.g., to lithium metal deposition depends on
      material properties as well as on the nano- und microstructure of the electrodes.
      In recent years a theoretical structure emerges, which opens the possibility to
      establish a systematic modeling strategy from atomistic to continuum scale to
      capture and couple the relevant phenomena on each scale. We outline the building
      blocks for such a systematic approach and discuss in detail a rigorous approach
      for the continuum scale based on rational thermodynamics and homogenization
      theories. Our focus is on the development of a systematic thermodynamically
      consistent theory for thermal phenomena in batteries at the microstructure scale
      and at the cell scale. We discuss the importance of carefully defining the
      continuum fields for being able to compare seemingly different phenomenological
      theories and for obtaining rules to determine unknown parameters of the theory by
      experiments or lower-scale theories. The resulting continuum models for the
      microscopic and the cell scale are numerically solved in full 3D resolution. The
      complex very localized distributions of heat sources in a microstructure of a
      battery and the problems of mapping these localized sources on an averaged porous
      electrode model are discussed by comparing the detailed 3D microstructure
      resolved simulations of the heat distribution with the result of the upscaled
      porous electrode model. It is shown, that not all heat sources that exist on the
      microstructure scale are represented in the averaged theory due to subtle
      cancellation effects of interface and bulk heat sources. Nevertheless, we find
      that in special cases the averaged thermal behavior can be captured very well by
      porous electrode theory. 

PMID- 25977871
TI  - Electrocatalysis on the nm scale.

PMID- 25977872
TI  - Patterning technique for gold nanoparticles on substrates using a focused
      electron beam.
AB  - We propose a novel patterning technique for gold nanoparticles on substrates that
      combines a chemical reaction with electron beam irradiation. First, gold
      nanoparticles are placed in a two-dimensional arrangement on the substrate. Then,
      particular nanoparticles are fixed on the substrate by irradiation with a focused
      electron beam to produce a desired pattern. Finally, the unfixed nanoparticles
      are removed. Using this technique, an array of gold nanoparticles, for example,
      in the form of a line or patterned over an area, are prepared on the substrate.
      This technique could contribute to the fabrication of plasmonic devices and other
      applications that require the controlled placement of gold nanoparticles on
      substrates. 

PMID- 25977874
TI  - Interaction of electromagnetic radiation in the 20-200 GHz frequency range with
      arrays of carbon nanotubes with ferromagnetic nanoparticles.
AB  - The interaction of electromagnetic radiation with a magnetic nanocomposite based
      on carbon nanotubes (CNT) is considered within the model of distributed random
      nanoparticles with a core-shell morphology. The approach is based on a system
      composed of a CNT conducting resistive matrix, ferromagnetic inductive
      nanoparticles and the capacitive interface between the CNT matrix and the
      nanoparticles, which form resonance resistive-inductive-capacitive circuits. It
      is shown that the influence of the resonant circuits leads to the emergence of
      specific resonances, namely peaks and valleys in the frequency dependence of the
      permeability of the nanocomposite, and in the frequency dependence of the
      reflection and transmission of electromagnetic radiation. 

PMID- 25977873
TI  - From lithium to sodium: cell chemistry of room temperature sodium-air and sodium
      sulfur batteries.
AB  - Research devoted to room temperature lithium-sulfur (Li/S8) and lithium-oxygen
      (Li/O2) batteries has significantly increased over the past ten years. The race
      to develop such cell systems is mainly motivated by the very high theoretical
      energy density and the abundance of sulfur and oxygen. The cell chemistry,
      however, is complex, and progress toward practical device development remains
      hampered by some fundamental key issues, which are currently being tackled by
      numerous approaches. Quite surprisingly, not much is known about the analogous
      sodium-based battery systems, although the already commercialized, high
      temperature Na/S8 and Na/NiCl2 batteries suggest that a rechargeable battery
      based on sodium is feasible on a large scale. Moreover, the natural abundance of
      sodium is an attractive benefit for the development of batteries based on low
      cost components. This review provides a summary of the state-of-the-art knowledge
      on lithium-sulfur and lithium-oxygen batteries and a direct comparison with the
      analogous sodium systems. The general properties, major benefits and challenges,
      recent strategies for performance improvements and general guidelines for further
      development are summarized and critically discussed. In general, the substitution
      of lithium for sodium has a strong impact on the overall properties of the cell
      reaction and differences in ion transport, phase stability, electrode potential,
      energy density, etc. can be thus expected. Whether these differences will benefit
      a more reversible cell chemistry is still an open question, but some of the first
      reports on room temperature Na/S8 and Na/O2 cells already show some exciting
      differences as compared to the established Li/S8 and Li/O2 systems. 

PMID- 25977875
TI  - Influence of operational parameters on the fluid-side mass transfer resistance
      observed in a packed bed bioreactor.
AB  - The influence of mass transfer on productivity as well as the performance of
      packed bed bioreactor was determined by varying a number of parameters; flow
      rate, glucose concentration and polymers (chitosan). Saccharomyces cerevisiae
      cells were immobilized in chitosan and non-chitosan coated alginate beads to
      demonstrate the effect on external mass transfer by substrate consumption time,
      lag phase and ethanol production. The results indicate that coating has a
      significant effect on the lag phase duration, being 30-40 min higher than non
      coated beads. After lag phase, no significant change was observed in both types
      of beads on consumption of glucose with the same flow rate. It was observed that
      by increasing flow rates; lag phase and glucose consumption time decreased. The
      reason is due to the reduction of external mass transfer as a result of increase
      in flow rate as glucose is easily transported to and from the beads surface by
      diffusion. It is observed that chitosan acts as barrier for transfer of substrate
      and products, in and out of beads, at initial time of fermentation as it shows
      longer lag phase for chitosan coated beads than non-coated. Glucose consumption
      at low flow rate was lower as compared to higher flow rates. The optimum
      combination of parameters consisting of higher flow rates 30-90 ml/min and
      between 10 and 20 g/l of glucose was found for maximum production of ethanol. 

PMID- 25977876
TI  - In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimer's
      disease with a high specific activity PET imaging agent [(18)F]flutemetamol.
AB  - BACKGROUND: The purpose of the study was to evaluate the applicability of (18) F
      labelled amyloid imaging positron emission tomography (PET) agent [ (18)
      F]flutemetamol to detect changes in brain beta-amyloid (Abeta) deposition in vivo
      in APP23, Tg2576 and APPswe-PS1dE9 mouse models of Alzheimer's disease. We
      expected that the high specific activity of [ (18) F]flutemetamol would make it
      an attractive small animal Abeta imaging agent. METHODS: [ (18) F]flutemetamol
      uptake in the mouse brain was evaluated in vivo at 9 to 22 months of age with an
      Inveon Multimodality PET/CT camera (Siemens Medical Solutions USA, Knoxville, TN,
      USA). Retention in the frontal cortex (FC) was evaluated by Logan distribution
      volume ratios (DVR) and FC/cerebellum (CB) ratios during the late washout phase
      (50 to 60 min). [ (18) F]flutemetamol binding to Abeta was also evaluated in
      brain slices by in vitro and ex vivo autoradiography. The amount of Abeta in the
      brain slices was determined with Thioflavin S and anti-Abeta1-40
      immunohistochemistry. RESULTS: In APP23 mice, [ (18) F]flutemetamol retention in
      the FC increased from 9 to 18 months. In younger mice, DVR and FC/CB50-60 were
      0.88 (0.81) and 0.88 (0.89) at 9 months (N = 2), and 0.98 (0.93) at 12 months (N
      = 1), respectively. In older mice, DVR and FC/CB50-60 were 1.16 (1.15) at 15
      months (N = 1), 1.13 (1.16) and 1.35 (1.35) at 18 months (N = 2), and 1.05 (1.31)
      at 21 months (N = 1). In Tg2576 mice, DVR and FC/CB50-60 showed modest increasing
      trends but also high variability. In APPswe-PS1dE9 mice, DVR and FC/CB50-60 did
      not increase with age. Thioflavin S and anti-Abeta1-40 positive Abeta deposits
      were present in all transgenic mice at 19 to 22 months, and they co-localized
      with [ (18) F]flutemetamol binding in the brain slices examined with in vitro and
      ex vivo autoradiography. CONCLUSIONS: Increased [ (18) F]flutemetamol retention
      in the brain was detected in old APP23 mice in vivo. However, the high specific
      activity of [ (18) F]flutemetamol did not provide a notable advantage in Tg2576
      and APPswe-PS1dE9 mice compared to the previously evaluated structural analogue
      [(11)C]PIB. For its practical benefits, [ (18) F]flutemetamol imaging with a
      suitable mouse model like APP23 is an attractive alternative.

PMID- 25977877
TI  - Influence of the amount of co-infused amino acids on post-therapeutic potassium
      levels in peptide receptor radionuclide therapy.
AB  - BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is routinely used for
      advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity,
      positively charged amino acids (AA) are co-infused. The aim of this study was to
      correlate the risk for therapy-related hyperkalaemia with the total amount of AA
      infused. METHODS: Twenty-two patients undergoing PRRT with standard activities of
      (177)Lu-DOTATATE/-TOC were monitored during two following treatment cycles with
      co-infusion of 75 and 50 g of AA (l-arginine and l-lysine), respectively. Mean
      serum levels of potassium and other parameters (glomerular filtration rate [GFR],
      creatinine, blood urea nitrogen [BUN], phosphate, chloride, lactate
      dehydrogenase) prior to, 4 h and 24 h after AA infusion were compared. RESULTS:
      Self-limiting hyperkalaemia (>5.0 mmol/l) resolving after 24 h occurred in 91%
      (20/22) of patients in both protocols. Potassium levels, BUN, creatinine, GFR,
      phosphate, chloride and LDH showed a similar range at 4 h after co-infusion of 75
      or 50 g of AA, respectively (p?>?0.05). Only GFR and creatinine levels at 24 h
      varied significantly between the two co-infusion protocols (p?<?0.05).
      CONCLUSIONS: Hyperkalaemia is a frequent side effect of AA infusion in PRRT.
      Varying the dose of co-infused amino acids did not impact on the incidence and
      severity of hyperkalaemia.

PMID- 25977878
TI  - Agonist signalling properties of radiotracers used for imaging of dopamine D2/3
      receptors.
AB  - BACKGROUND: Dopamine D2/3 receptor (D2/3R) agonist radiopharmaceuticals are
      considered superior to antagonists to detect dopamine release, e.g. induced by
      amphetamines. Agonists bind preferentially to the high-affinity state of the
      dopamine D2R, which has been proposed as the reason why agonists are more
      sensitive to detect dopamine release than antagonist radiopharmaceuticals, but
      this theory has been challenged. Interestingly, not all agonists similarly
      activate the classic cyclic adenosine mono phosphate (cAMP) and the ?-arrestin-2
      pathway, some stimulate preferentially one of these pathways; a phenomenon called
      biased agonism. Because these pathways can be affected separately by pathologies
      or drugs (including dopamine releasers), it is important to know how agonist
      radiotracers act on these pathways. Therefore, we characterized the intracellular
      signalling of the well-known D2/3R agonist radiopharmaceuticals NPA and PHNO and
      of several novel D2/3R agonists. METHODS: cAMP accumulation and ?-arrestin-2
      recruitment were measured on cells expressing human D2R. RESULTS: All tested
      agonists showed (almost) full agonism in both pathways. CONCLUSIONS: The tested
      D2/3R agonist radiopharmaceuticals did not exhibit biased agonism in vitro.
      Consequently, it is likely that drugs (including psychostimulants like
      amphetamines) and/or pathologies that influence the cAMP and/or the ?-arrestin-2
      pathway may influence the binding of these radiopharmaceuticals.

PMID- 25977879
TI  - Evaluation of repeated [(18)F]EF5 PET/CT scans and tumor growth rate in
      experimental head and neck carcinomas.
AB  - BACKGROUND: Tumor hypoxia is linked to invasion and metastasis but whether this
      associates with tumor growth rate is not well understood. We aimed to study the
      relationship between hypoxia evaluated with the positron emission tomography
      (PET) tracer [(18)F]EF5 and tumor growth. Our second goal was to assess the
      variability in the uptake of [(18)F]EF5 in tumor between two scans. METHODS: Four
      human head and neck squamous cell carcinoma (UT-SCC) cell lines were xenografted
      in flank or neck of nude mice, and tumor size was closely monitored over the
      study period. The tumors were clearly visible when the first [(18)F]EF5 scan was
      acquired. After an exponential growth phase, the tumors were imaged again with
      [(18)F]EF5 and also with (18)F-fluorodeoxyglucose ([(18)F]FDG). RESULTS: There
      was a clear correlation between the percentage of tumor growth rate per day and
      the [(18)F]EF5 uptake in the latter scan (r = 0.766, p = 0.01). The uptake of
      [(18)F]EF5 in the first scan and the uptake of [(18)F]FDG did not significantly
      correlate with the tumor growth rate. We also observed considerable variations in
      the uptake of [(18)F]EF5 between the two scans. CONCLUSIONS: The uptake of
      [(18)F]EF5 in the late phase of exponential tumor growth is associated with the
      tumor growth rate in mice bearing HNC xenografts.

PMID- 25977880
TI  - Prediction of clinically relevant hyperkalemia in patients treated with peptide
      receptor radionuclide therapy.
AB  - BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is applied in patients
      with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent
      nephrotoxicity. The aims of this study were to correlate the incidence of AA
      induced hyperkalemia (HK) (>=5.0 mmol/l) and to identify predictors of AA-induced
      severe HK (>6.0). METHODS: In 38 patients, standard activity of (177)Lu-labelled
      somatostatin analogs was administered. Pre-therapeutic kidney function was
      assessed by renal scintigraphy and laboratory tests. For kidney protection, AA
      was co-infused. Biochemical parameters (potassium, glomerular filtration rate,
      creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate
      dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion.
      Incidence of HK (>=5.0) was correlated with pre-therapeutic kidney function and
      serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were
      computed and prospectively validated. RESULTS: At 4 h, HK (>=5.0) was present in
      94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre
      therapeutic kidney function did not correlate with the incidence of severe HK.
      Increases in K(+) were significantly correlated with decreases in phosphate (r = 
      0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of
      >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in
      predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard
      serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a
      sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK
      >6.0 (accuracy = 81.6%). CONCLUSIONS: A combination of serum parameters predicted
      prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining
      its potential utility for identifying 'high-risk' patients prone to PRRT.

PMID- 25977881
TI  - Evaluation of the specificity of [(18)F]fludarabine PET/CT in a xenograft model
      of follicular lymphoma: comparison with [(18)F]FDG and impact of rituximab
      therapy.
AB  - BACKGROUND: [(18)F]Fludarabine is a novel positron emission tomography (PET)
      radiotracer for imaging lymphoma. The purpose of this preclinical study was to
      evaluate the robustness of [(18)F]fludarabine during rituximab therapy. In
      addition, a comparison was made between [(18)F]fludarabine and
      [(18)F]fluorodeoxyglucose ([(18)F]FDG) with regard to their concordance with
      histologically derived data. METHODS: CB17-SCID mice bearing human follicular
      DOHH-2 lymphoma were treated once weekly with rituximab (10 mg/kg) or
      physiological saline over 3 weeks. To obtain the tracer uptake in the
      metabolically active volume of the tumour (MAVT), a background-level threshold
      was applied to the volume of interest (VOI) defined on computed tomography (CT)
      image. The tumour uptake analysis was performed with MAVT-based segmentation for
      data analysis of sequential [(18)F]fludarabine PET/CT studies and with total
      tumour-based segmentation for comparison with histologically derived data.
      RESULTS: The correlation between the MAVT and [(18)F]fludarabine accumulation
      (%ID) in those viable tissues was equally significant for both vehicle- or
      rituximab-treated mice; for these latter, the presence of lymphoid tissues at the
      end of imaging sessions was confirmed histologically. A stronger correlation was
      demonstrated between quantitative values extracted from [(18)F]fludarabine-PET
      and histology (r (2) = 0.91, p < 0.001) when compared to [(18)F]FDG-PET (r (2) =
      0.55, p = 0.03). CONCLUSIONS: [(18)F]Fludarabine uptake in the follicular
      lymphoma model compared favourably with [(18)F]FDG in terms of specificity for
      PET imaging and also remained robust for persistent viable tissues following
      rituximab therapy. [(18)F]Fludarabine PET/CT may be a promising approach to
      evaluate lymphoma, including their surveillance during therapy.

PMID- 25977882
TI  - Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA
      peptides, correlation to prognostic markers, and implications for targeted
      radiotherapy.
AB  - BACKGROUND: High-grade gliomas (HGGs) express somatostatin receptors (SSTR),
      rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our
      purpose was to evaluate the potential of (68)Ga-DOTA-1-Nal(3)-octreotide ((68)Ga
      DOTANOC) or (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTATOC) to target SSTR subtype
      2 (SSTR2) in HGGs, and to study the association between SSTR2 expression and
      established biomarkers. METHODS: Twenty-seven patients (mean age 52 years) with
      primary or recurrent HGG prospectively underwent (68)Ga-DOTA-peptide positron
      emission tomography/computed tomography (PET/CT) before resection. Maximum
      standardized uptake values (SUVmax) and receptor binding potential (BP) were
      calculated on PET/CT and disruption of blood-brain barrier (BBB) from contrast
      enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume
      concordance between PET and MRI-T1-Gad was assessed by Dice similarity
      coefficient (DC) and correlation by Spearman's rank. Immunohistochemically
      determined SSTR2 status was compared to receptor imaging findings, prognostic
      biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and
      multivariate Cox regression, respectively. RESULTS: All 19 HGGs with disrupted
      BBB demonstrated tracer uptake. Tumor SUVmax (2.25 +/- 1.33) correlated with MRI
      T1-Gad (r = 0.713, P = 0.001) although DC 0.41 +/- 0.19 suggested limited
      concordance. SSTR2 immunohistochemistry was regarded as positive in nine HGGs
      (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR2
      expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma
      component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P
      = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P =
      0.015). CONCLUSIONS: In HGGs, uptake of (68)Ga-DOTA-peptides is associated with
      disrupted BBB and cannot be predicted by SSTR2 immunohistochemistry. Thus, PET/CT
      shows limited value to detect HGGs suitable for PRRT. However, high SSTR2
      expression portends favorable outcome along with established biomarkers such as
      IDH1 mutation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01460706.

PMID- 25977883
TI  - Differentiation of malignant tumours from granulomas by using dynamic [(18)F]
      fluoro-L-alpha-methyltyrosine positron emission tomography.
AB  - BACKGROUND: Previous clinical studies have revealed the potential of [(18)F]
      fluoro-L-alpha-methyltyrosine ((18)F-FAMT) for the differential diagnosis of
      malignant tumours from sarcoidosis. However, one concern regarding the
      differential diagnosis with (18)F-FAMT is the possibility of false negatives
      given the small absolute uptake of (18)F-FAMT that has been observed in some
      malignant tumours. The aim of this study was to evaluate a usefulness of dynamic
      (18)F-FAMT positron emission tomography (PET) for differentiating malignant
      tumours from granulomas. METHODS: Rats bearing both granulomas (Mycobacterium
      bovis bacillus Calmette-Guerin (BCG)-induced) and tumours (C6 glioma cell
      induced) underwent dynamic 2-deoxy-2-[(18)F]-fluoro-D-glucose ((18)F-FDG) PET and
      (18)F-FAMT PET for 120 min on consecutive days. Time-activity curves, static
      images, mean standardized uptake values (SUVs) and the SUV ratios (SUVRs;
      calculated by dividing SUV at each time point by that of 2 min after injection)
      were assessed. RESULTS: In tumours, (18)F-FAMT showed a shoulder peak immediately
      after the initial distribution followed by gradual clearance compared with
      granulomas. Although the mean SUV in the tumours (1.00 +/- 0.10) was
      significantly higher than that in the granulomas (0.88 +/- 0.12), a large overlap
      was observed. In contrast, the SUVR was markedly higher in tumours than in
      granulomas (50 min/2 min, 0.72 +/- 0.06 and 0.56 +/- 0.05, respectively) with no
      overlap. The dynamic patterns, SUVR, and mean SUV of (18)F-FDG in the granulomas
      were comparable to those in the tumours. CONCLUSIONS: Dynamic (18)F-FAMT and SUVR
      analysis might compensate for the current limitations and help in improving the
      diagnostic accuracy of (18)F-FAMT.

PMID- 25977884
TI  - Lapatinib access into normal brain and brain metastases in patients with Her-2
      overexpressing breast cancer.
AB  - BACKGROUND: Brain metastases are common in human epidermal growth factor receptor
      (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain
      is key to management of cranial disease. In this study, positron emission
      tomography (PET) scanning after administration of radiolabelled lapatinib was
      used to obtain direct evidence of cranial drug access. METHODS: Patients with Her
      2+ metastatic breast cancer either with at least one 1-cm diameter brain
      metastasis or without brain metastases underwent dynamic carbon-11 radiolabelled
      lapatinib ([(11)C]lapatinib)-PET. Less than 20 MUg of [(11)C]lapatinib was
      administered before and after 8 days of oral lapatinib (1,500 mg once daily).
      Radial arterial blood sampling was performed throughout the 90-min scan. The
      contribution of blood volume activity to the tissue signal was excluded to
      calculate lapatinib uptake in normal brain and metastases. Partitioning of
      radioactivity between plasma and tissue (V T) was calculated and the tissue
      concentration of lapatinib derived. Plasma lapatinib levels were measured and
      adverse events noted. RESULTS: Six patients (three with brain metastases) were
      recruited. About 80% plasma radioactivity corresponded to intact [(11)C]lapatinib
      after 60 min. PET signal in the brain corresponded to circulating radioactivity
      levels, with no [(11)C]lapatinib uptake observed in normal brain tissue. In
      contrast, radioactivity uptake in cranial metastases was significantly higher (p
      = 0.002) than that could be accounted by circulating radioactivity levels,
      consistent with [(11)C]lapatinib uptake in brain metastases. There was no
      difference in lapatinib uptake between the baseline and day 8 scans, suggesting
      no effect of increased drug access by inhibition of the drug efflux proteins by
      therapeutic doses of lapatinib. CONCLUSIONS: Increased lapatinib uptake was
      observed in brain metastases but not in normal brain. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01290354.

PMID- 25977885
TI  - Tensile properties of the rectal and sigmoid colon: a comparative analysis of
      human and porcine tissue.
AB  - For many patients, rectal catheters are an effective means to manage bowel
      incontinence. Unfortunately, the incidence of catheter leakage in these patients
      remains troublingly high. Matching the mechanical properties of the catheter and
      the surrounding tissue may improve the catheter seal and reduce leakage. However,
      little data is available on the mechanical properties of colorectal tissue.
      Therefore, our group examined the mechanical properties of colorectal tissue
      obtained from both a common animal model and humans. Uniaxial tension tests were
      performed to determine the effects of location, orientation, and species (porcine
      and human) on bowel tissue tensile mechanical properties. Bowel tissue ultimate
      strength, elongation at failure, and elastic modulus were derived from these
      tests and statistically analyzed. Ultimate tensile strength (0.58 MPa, 0.87 MPa),
      elongation at failure (113.19%, 62.81%), and elastic modulus (1.83 MPa, 5.18 MPa)
      for porcine and human samples respectively exhibited significant differences
      based on species. Generally, human tissues were stronger and less compliant than
      their porcine counterparts. Furthermore, harvest site location and testing
      orientation significantly affected several mechanical properties in porcine
      derived tissues, but very few in human tissues. The data suggests that porcine
      colorectal tissue does not accurately model human colorectal tissue mechanical
      properties. Ultimately, the tensile properties reported herein may be used to
      help guide the design of next generation rectal catheters with tissue mimetic
      properties, as well as aid in the development of physical and computer based
      bowel models. 

PMID- 25977886
TI  - Structural characterization and colour of MgxCu3-xV2O8 (0 <= x <= 3) and MgyCu2
      yV2O7 (0 <= y <= 2) compositions.
AB  - In this study, MgxCu3-xV2O8 (0 <= x <= 3) and MgyCu2-yV2O7 (0 <= y <= 2)
      compositions were synthesized by the chemical coprecipitation method and
      characterized by X-ray diffraction, UV-vis-NIR spectroscopy and CIE L* a* b*
      parameters measurements. Melting points of compounds Cu3V2O8 and Cu2V2O7 are 780
      degrees C and 790 degrees C, respectively. The addition of small amounts of Mg
      (II), MgxCu3-xV2O8 (x < 1.0) and MgyCu2-yV2O7 (y < 0.5) fused compositions, was
      not sufficient to stabilize structures at 800 degrees C. For the Mg2CuV2O8 (x =
      2.0) composition fired at 800 degrees C, Mg (II) incorporated into the monoclinic
      Cu3V2O8 structure stabilizes this crystalline phase. At 1000 degrees C,
      orthorhombic Mg3V2O8 structure from this composition was obtained. Solid
      solutions with orthorhombic symmetry were detected from the prepared compositions
      fired at 1000 degrees C when 1.0 <= x <= 3.0. The difference of coloration of Cu,
      Mg vanadates might be explained by the presence of a strong charge transfer band
      in visible spectra. 

PMID- 25977887
TI  - Acute adult-onset still's disease presenting as pulmonary hemorrhage, urticaria,
      angioedema and leukemoid reaction: a case report and literature review.
AB  - INTRODUCTION: Adult-onset Still's disease is a rare systemic inflammatory
      disorder of unknown aetiology characterized by the classic triad of persistent
      high spiking fevers, joint pain and a distinctive salmon-colored bumpy rash
      however, the multiorgan involvement can be present. CASE DESCRIPTION: A 40-year
      old woman previously healthy was referred to our hospital with 7 days of high
      fever and generalized arthralgia, The physical exam revealed angioneurotic edema
      detected on soles, palms and tongue and widespread red, urticated plaques in a
      symmetrical distribution affecting the arms, dorsal hands, upper and lower chest
      and back. Followed 5 days later by fever, the patient presented dyspnea, cough
      and hypoxemia, the imaging studies showed unilateral consolidation and pleural
      effusion. The bronchoscopy with bronchoalveolar lavage and skin biopsy were
      consistent with neutrophilic urticarial. The hematological disorders, infections
      and other autoimmune diseases were excluded. DISCUSSION AND EVALUATION: The
      diagnosis of adult-onset Still's disease can be very difficult. There are no
      specific tests and reliance is usually placed on a symptom complex and the well
      described typical rash seen in most patients. In recent years, however, other
      cutaneous manifestations of Adult-onset Still's disease have been reported but
      these are not so well known. CONCLUSIONS: The evidence of rare manifestations is
      growing and the early clinical presentation of Adult-onset Still's is extremely
      variable, making diagnosis difficult. For this reason, data on early clinical
      presentation of the disease are of interest. We reported the first case of acute
      Adult-onset Still's disease with the association of pulmonary hemorrhage,
      urticaria and angioedema including a rare systemic manifestation as leukemoid
      reaction.

PMID- 25977888
TI  - Identification of QTLs and possible candidate genes conferring sheath blight
      resistance in rice (Oryza sativa L.).
AB  - Sheath blight, caused by the pathogenic fungus Rhizoctonia solani Kuhn, is one of
      the most devastating diseases in rice. Breeders have always faced challenges in
      acquiring reliable and absolute resistance to this disease in existing rice
      germplasm. In this context, 40 rice germplasm including eight wild, four
      landraces, twenty- six cultivated and two advanced breeding lines were screened
      utilizing the colonized bits of typha. Except Tetep and ARC10531 which expressed
      moderate level of resistance to the disease, none could be found to be
      authentically resistant. In order to map the quantitative trait loci (QTLs)
      governing the sheath blight resistance, two mapping populations (F2 and BC1F2)
      were developed from the cross BPT-5204/ARC10531. Utilizing composite interval
      mapping analysis, 9 QTLs mapped to five different chromosomes were identified
      with phenotypic variance ranging from 8.40 to 21.76%. Two SSR markers namely
      RM336 and RM205 were found to be closely associated with the major QTLs qshb7.3
      and qshb9.2 respectively and were attested as well in BC1F2 population by bulk
      segregant analysis approach. A hypothetical beta 1-3 glucanase with other 31
      candidate genes were identified in silico utilizing rice database RAP-DB within
      the identified QTL region qshb9.2. A detailed insight into these candidate genes
      will facilitate at molecular level the intricate nature of sheath blight, a step
      forward towards functional genomics. 

PMID- 25977889
TI  - Ontogeny and morphological variability of shell in populations of Leptinaria
      unilamellata (d'Orbigny, 1835) (Mollusca, Pulmonata, Subulinidae).
AB  - BACKGROUND: Recent studies concerning species of land snails have revealed that
      the shell morphometrics can provide evidence of the differentiation among
      populations. In many cases, the morphologic analysis combined with the
      investigation of molecular variability, can support changes in taxonomy of
      studied groups. In this sense, the study of shell morphometry during snail
      development can contribute to the understanding of the structural mechanisms that
      creates the diversity observed. DESCRIPTION: The morphological and ontogenetic
      pattern differences were collected among snails from four different populations,
      kept under the same laboratorial conditions. It was possible to distinguish
      characteristic shell morphometrics for snails from each population. The snails
      from Barra Mansa and Floriano, locations with smaller precipitation indexes
      presented smaller shell aperture values. The results are discussed in terms of
      the role of the reproductive strategy of this species as a factor determining
      shell shape. CONCLUSIONS: Differences in growth allometry indicated that the
      whole shell forming process is different among the populations, not only the
      final form of the adult's shell. Some allometry relationships indicated that,
      during the snails' development, the increase in shell width is not proportional
      to the increase of the width and height of the shell aperture. Thus, there is
      possibly an antagonism between the adoption of K-strategy and protection against
      desiccation. Since the spire indices of L. unilamellata morphotypes cannot be
      explained by physical functional aspects, the most likely explanation is the
      reproductive strategy of this species.

PMID- 25977891
TI  - Exploring the factors influencing the cloud computing adoption: a systematic
      study on cloud migration.
AB  - Today, most of the organizations trust on their age old legacy applications, to
      support their business-critical systems. However, there are several critical
      concerns, as maintainability and scalability issues, associated with the legacy
      system. In this background, cloud services offer a more agile and cost effective
      platform, to support business applications and IT infrastructure. As the adoption
      of cloud services has been increasing recently and so has been the academic
      research in cloud migration. However, there is a genuine need of secondary study
      to further strengthen this research. The primary objective of this paper is to
      scientifically and systematically identify, categorize and compare the existing
      research work in the area of legacy to cloud migration. The paper has also
      endeavored to consolidate the research on Security issues, which is prime factor
      hindering the adoption of cloud through classifying the studies on secure cloud
      migration. SLR (Systematic Literature Review) of thirty selected papers,
      published from 2009 to 2014 was conducted to properly understand the nuances of
      the security framework. To categorize the selected studies, authors have proposed
      a conceptual model for cloud migration which has resulted in a resource base of
      existing solutions for cloud migration. This study concludes that cloud migration
      research is in seminal stage but simultaneously it is also evolving and maturing,
      with increasing participation from academics and industry alike. The paper also
      identifies the need for a secure migration model, which can fortify
      organization's trust into cloud migration and facilitate necessary tool support
      to automate the migration process. 

PMID- 25977890
TI  - Immune cells subpopulations in cerebrospinal fluid and peripheral blood of
      patients with Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: There is growing evidence supporting the role of inflammation in
      aneurysmal subarachnoid hemorrhage (aSAH) pathophysiology and it is of great
      interest to elucidate which immune mechanisms are involved. METHODS: 12 aSAH
      patients and 28 healthy controls were enrolled prospectively. We assessed
      leukocytes subpopulations and their activation status by flow cytometry in
      cerebrospinal fluid (CSF) and peripheral blood (PB) of SAH patients at the same
      time and in PB of controls. RESULTS: Monocytes and neutrophils were activated in
      CSF of aSAH patients. The percentage of CD14(++)CD16(+) monocytes were higher in
      CSF than in PB of aSAH patients, and were also increased in PB of aSAH patients
      compared with controls. An enhanced expression of CD69 was shown in CSF
      neutrophils compared with PB in aSAH patients. PB of aSAH patients showed lower
      percentage of total lymphocytes compared with controls PB. Additionally,
      lymphocytes were activated in CSF and PB of aSAH patients. CD4(+) and CD8(+) T
      cells had a decreased expression on CD3 and higher levels of CD69 in CSF compared
      with PB in aSAH patients. Moreover, PB CD4(+) and CD8(+) T cells of aSAH patients
      were activated compared with controls. Additionally, CD28 expression was
      decreased on CSF T lymphocytes. CONCLUSIONS: Our data suggest an important
      recruitment of leukocytes to the site of injury in aSAH as well as an increased
      activation at this level. Overall, these results indicate that aSAH probably
      stimulates both the innate and adaptive immune responses.

PMID- 25977892
TI  - Calcific panniculitis and nasopharyngeal cancer-associated adult-onset
      dermatomyositis: a case report and literature review.
AB  - Panniculitis is an uncommon cutaneous manifestation in dermatomyositis. It not
      only occurs in idiopathic dermatomyositis, but also rarely occurs in the setting
      of malignancy-associated dermatomyositis. Calcinosis cutis is also less likely to
      be found in adult-onset dermatomyositis. In malignancy-associated
      dermatomyositis, panniculitis can precede, concur, or follow the diagnosis of
      malignancy. We report the case of a 26-year-old Thai female with calcific
      panniculitis in the setting of adult-onset dermatomyositis associated with
      nasopharyngeal cancer. The clinical course of calcific panniculitis in our case
      was not parallel to the course of malignancy. Calcific panniculitis can appear
      many years after, despite the remission of the cancer. A thorough review of the
      previously reported literature is also provided. 

PMID- 25977893
TI  - Comparative performance of modified full-length and truncated Bacillus
      thuringiensis-cry1Ac genes in transgenic tomato.
AB  - BACKGROUND: Bt-cry1Ac gene has been reputedly effective against Helicoverpa
      armigera a notorious lepidopteran pest. Reports on the expression of full-length
      and truncated cry1Ac genes in plants for effective resistance against Helicoverpa
      sp. have been documented however, their performance is still ambiguous. Moreover,
      the question remains to be addressed that truncation of 3' end of the native gene
      was documented and suggested for active insecticidal toxin production while the
      most successful transgenic event(s) of commercialized-cotton are based on full
      length of the cry gene. Therefore, we performed a comparative study on the
      efficacy of the two versions of cry1Ac genes (full-length: 3,510 bp and
      truncated: 1,845 bp) in T0 and T1 transgenic tomato plants and analyzed the
      extent of protection against H. armigera and also compared the results with our
      previous findings related to a successful transgenic tomato line Ab25E,
      expressing cry1Ab gene. The integration of cry1Ac gene(s) in T0 transgenic plants
      and its inheritance in T1 progeny was observed by PCR, RT-PCR and Southern blot
      hybridization analysis while, the toxin integrity, expression and toxicity was
      monitored by Western immunoassay, DAS-ELISA and insect bioassay respectively.
      RESULTS: An average transformation frequency and Bt-Cry protein content of 16.93
      +/- 2.10 and 0.0020-0.0128% of total soluble protein (TSP) was obtained with
      pRD400 vector (Trcry1Ac) while, a much lower value of 9.30 +/- 2.041 and 0.0001 -
      0.0026% of TSP was observed with pNBRI-1 vector (Flcry1Ac), respectively. The
      promising Trcry1Ac T0 transgenic plants and their T1 progeny gave full protection
      from H. armigera. Although Flcry1Ac gene showed lower transformation frequency
      and lower expression, it showed higher toxicity to H. armigera when compared with
      truncated Trcry1Ac gene. CONCLUSIONS: The full-length cry1Ac gene can be
      redesigned for higher expression and performance in dicots or a hybrid gene could
      be designed having a blend of strong receptor binding and stable expression
      characteristics for enhanced efficacy and toxicity to the susceptible insects.

PMID- 25977894
TI  - The bud midge Prodiplosis longifila: Damage characteristics, potential
      distribution and presence on a new crop host in Colombia.
AB  - The Dipteran Prodiplosis longifila is a severe pest, mainly of Solanaceae, in
      South America and some years ago it damaged Tahiti lime crops in the United
      States. It is a potential invasive pest. Despite its presence in Colombia,
      nothing is known regarding the taxonomic identification of P. longifila or the
      characteristics of the damage it produces. Moreover, the current and potential
      distributions of this pest are unknown. To determine these factors, P. longifila
      was sampled in several Solanaceae- and Citrus (x) latifolia (Tahiti lime)
      producing areas in Colombia. The larvae consumed tender foliage, flowers and
      fruits in tomato, fruits in sweet pepper, and buds in Tahiti lime. P. longifila
      was not found in asparagus or in potatoes. Its presence in Tahiti lime was
      previously unknown in Colombia. Adults recovered in the laboratory were
      taxonomically identified using male morphological characteristics such as the
      shapes of the genitalia, antenna and wing. P. longifila was found in the Andean
      region of Colombia. The ecological niche model for populations found in tomato
      suggests that P. longifila is limited in its distribution by altitude and
      variables associated with temperature and precipitation. The highest probability
      of occurrence is in areas where tomato, sweet pepper and the new host, Tahiti
      lime, are grown. Therefore, it is necessary to implement preventive measures,
      such as planting tomato materials free of P. longifila larvae, in areas where the
      pest is not yet present but where there is the potential for its development. 

PMID- 25977895
TI  - Predictors of European League Against Rheumatism (EULAR) good response, DAS-28
      remission and sustained responses to TNF-inhibitors in rheumatoid arthritis: a
      prospective study in refractory disease.
AB  - The aim of this study was to survey factors related to EULAR good response, the
      DAS-28 definition of remission, ACR 50 response, sustained response to tumor
      necrosis factor inhibitors (TNF-I) therapy in biologic naive patients with
      refractory rheumatoid arthritis. This was a single center observational clinical
      prospective 2 years' study, EULAR response criteria, DAS 28, HAQ and radiographic
      changes were recorded. Eighty patients included (64 females and 16 males, mean
      age was 48.4 + -17.9 years, mean disease duration 7.3 + -5.9 years). At 6 months
      70% achieved EULAR good response, 51.8% achieved DAS-28 remission. Good
      response/sustained responses inversely correlated with baseline DAS-28 and
      radiographic erosions P <0.05. EULAR good response/remission by 6 months,
      sustained response at 2 years positively correlated with the decline in RF titers
      (r = 0.33, P < 0.05 & r = 0.30, P < 0.03 respectively), negatively correlated
      with the baseline HAQ. Regression analysis identified higher serum hemoglobin
      concentration, lower baseline HAQ scores, and the absence of radiographic
      erosions as significant predictors of good as well as sustained responses after
      adjustment for potential covariates. Methotrexate was associated with favorable
      responses and remission at 6 months (ORs = 1.13, 1.30 respectively). The study
      concluded that a lower baseline DAS-28 and HAQ scores, the lack of radiographic
      erosions favored EULAR good response and were significant predictors of sustained
      response to TNF-I. 

PMID- 25977896
TI  - Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and
      neck cancer: a meta-analysis of the 5-year efficacy and safety.
AB  - BACKGROUND: The objective of this study was to compare the efficacy and safety of
      taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) with
      cisplatin plus fluorouracil (PF) regimen by a meta-analysis of data retrieved
      from the literature. METHODS: Seven randomized clinical trials were identified,
      which included patients with advanced head and neck cancer who underwent
      induction chemotherapy with either a Tax-PF or PF protocol. The outcomes included
      the 3-year and 5-year overall survival (OS) and progression-free survival (PFS),
      overall response rate (ORR) and different types of adverse events. RESULTS: The 3
      year OS rate (HR: 1.14; 95% CI: 1.03 to 1.25; P = 0.008), 3-year PFS rate (HR:
      1.24; 95% CI: 1.08 to 1.43; P = 0.002), 5-year OS rate (HR: 1.30; 95% CI, 1.09 to
      1.55;P = 0.003), 5-year PFS rate (HR: 1.39; 95% CI, 1.14 to 1.70; P = 0.001) and
      ORR to chemotherapy (OR 1.66; 95% CI, 1.35 to 2.05; P < 0.001) of the patients in
      the Tax-PF group were statistically superior to those in the PF group. In terms
      of toxicities, the incidence of febrile neutropenia (OR 2.36; 95% CI, 1.62 to
      3.46; P < 0.001), alopecia (OR 8.22; 95% CI, 3.99 to 16.92; P < 0.001), diarrhea
      (OR 1.57; 95% CI, 1.05 to 2.36; P = 0.03) and leukopenia (OR 2.79; 95% CI, 1.86
      to 4.21; P < 0.001) was higher in the Tax-PF group. CONCLUSION: The Tax-PF
      induction chemotherapy improved PFS and OS, and the ORR was better as compared to
      PF-based therapy regimens at the cost of a higher incidence of adverse events.

PMID- 25977897
TI  - Off-label use of cancer therapies in women diagnosed with breast cancer in the
      United States.
AB  - PURPOSE: To determine the level of off-label cancer therapy use in a population
      of female breast cancer patients and to establish whether this use was evidence
      based. METHODS: A study was conducted by sampling Cerner's data warehouse for all
      women diagnosed with breast cancer between January 2000 and June 2009 who
      received at least one cancer therapy approved by the US-FDA during the study
      period. Drug encounters were considered off-label if the circumstances of use did
      not match the age or medical diagnoses specified on the product label at the time
      of study. The level of evidence for the use of these drugs in a breast cancer
      setting was evaluated from randomized phase III trials using a tiered approach.
      RESULTS: The study included 2,663 women with a median age of 59 years. A total of
      1,636 off-label encounters were recorded, representing 13.0% of all encounters.
      Of the 65 cancer therapies investigated, 55.4% were prescribed off-label. The
      drugs with the highest off-label use were, in a descending order, vinorelbine,
      carboplatin, bevacizumab, leuprolide, liposomal doxorubicin and cisplatin. Most
      off-label encounters were evidence-based and more likely to be associated with
      private insurance coverage, younger age, ethnicities other than Caucasian,
      smaller treatment centres and drugs with limited labeled indications that have a
      longer market history. CONCLUSIONS: Off-label prescribing is common practice in
      oncology and is an integral component of breast cancer treatment strategies.
      While this practice tends to be associated with specific socio-demographic
      factors and disease characteristics, the majority of off-label encounters appear
      to be evidence-based.

PMID- 25977898
TI  - Comparison of mechanical and manual bone marrow puncture needle for intraosseous
      access; a randomized simulation trial.
AB  - BACKGROUND: During resuscitation, when it is difficult or impossible to establish
      peripheral venous access, intraosseous route (IO) is considered as an alternative
      to a central venous line. However, it is sometimes difficult for obtain IO access
      with conventional manual bone puncture needle. Recently, powered mechanical bone
      marrow needle was developed. We compared the performance of the manual and
      mechanical bone marrow puncture needle for adult, child and infant simulation.
      METHODS: 22 anesthesiologists, who has never used bone marrow puncture needle,
      performed manual (DickmanTM, Cook Medical) or mechanical (EZ-IOTM, Teleflex) bone
      marrow puncture to simulated adult, child and infant tibia. Puncture success
      rate, insertion time, and subjective difficulty utilizing visual analogue scale
      was assessed. RESULTS: In adult settings, with the manual bone marrow needle,
      only 3 of 22 participants could succeed in the IO route keep, while all
      participants did in the mechanical bone marrow puncture needle (P < 0.001). In
      child and infant settings, all trials were successful in both manual and
      mechanical bone marrow puncture needles (P = 1.00). In adult simulations, IO
      insertion took significantly longer with manual bone marrow puncture (54.8 +/-
      15.8 s) than without compressions (3.7 +/- 2.1 s; P < 0.001). In child and infant
      simulations, the IO insertion time was significantly smaller in mechanical trials
      than in manual ones (child simulation; manual 9.3 +/- 4.6 s, mechanical 2.2 +/-
      0.8 s, P < 0.001, infant simulation; manual 2.0 +/- 1.1 s, mechanical 1.5 +/- 0.8
      s, P = 0.003). Although the VAS score was not significantly higher with manual
      trials than in mechanical trials among the three simulations (adult simulation, P
      < 0.001, child simulation, P < 0.001, infant simulation P = 0.006). CONCLUSIONS:
      We conclude that in simulations managed by anesthesiologists who had no clinical
      experiences with bone marrow puncture, the mechanical bone puncture needle
      performed better than the manual one for emergency IO route access.

PMID- 25977899
TI  - Gestational diabetes mellitus: challenges in diagnosis and management.
AB  - Gestational diabetes mellitus (GDM) is a well-characterized disease affecting a
      significant population of pregnant women worldwide. It has been widely linked to
      undue weight gain associated with factors such as diet, obesity, family history,
      and ethnicity. Poorly controlled GDM results in maternal and fetal morbidity and
      mortality. Improved outcomes therefore rely on early diagnosis and tight
      glycaemic control. While straightforward protocols exist for screening and
      management of diabetes mellitus in the general population, management of GDM
      remains controversial with conflicting guidelines and treatment protocols. This
      review highlights the diagnostic and management options for GDM in light of
      recent advances in care. 

PMID- 25977900
TI  - Oncolytic virotherapy for ovarian cancer.
AB  - In the past two decades, more than 20 viruses with selective tropism for tumor
      cells have been developed as oncolytic viruses (OVs) for treatments of a variety
      of malignancies. Of these viruses, eleven have been tested in human ovarian
      cancer models in preclinical studies. So far, nine phase I or II clinical trials
      have been conducted or initiated using four different types of OVs in patients
      with recurrent ovarian cancers. In this article, we summarize the different OVs
      that are being assessed as therapeutics for ovarian cancer. We also present an
      overview of recent advances in identification of key genetic or immune-response
      pathways involved in tumorigenesis of ovarian cancer, which provides a better
      understanding of the tumor specificities and oncolytic properties of OVs. In
      addition, we discuss how next-generation OVs could be genetically modified or
      integrated into multimodality regimens to improve clinical outcomes based on
      recent advances in ovarian cancer biology.

PMID- 25977901
TI  - Characteristics and treatments of large cystic brain metastasis: radiosurgery and
      stereotactic aspiration.
AB  - Brain metastasis represents one of the most common causes of intracranial tumors
      in adults, and the incidence of brain metastasis continues to rise due to the
      increasing survival of cancer patients. Yet, the development of cystic brain
      metastasis remains a relatively rare occurrence. In this review, we describe the
      characteristics of cystic brain metastasis and evaluate the combined use of
      stereotactic aspiration and radiosurgery in treating large cystic brain
      metastasis. The results of several studies show that stereotactic radiosurgery
      produces comparable local tumor control and survival rates as other surgery
      protocols. When the size of the tumor interferes with radiosurgery, stereotactic
      aspiration of the metastasis should be considered to reduce the target volume as
      well as decreasing the chance of radiation induced necrosis and providing
      symptomatic relief from mass effect. The combined use of stereotactic aspiration
      and radiosurgery has strong implications in improving patient outcomes. 

PMID- 25977903
TI  - Validation of housekeeping genes for gene expression analysis in glioblastoma
      using quantitative real-time polymerase chain reaction.
AB  - BACKGROUND: Quantitative real-time polymerase chain reaction (qPCR) is the most
      reliable tool for gene expression studies. Selection of housekeeping genes (HKGs)
      that are having most stable expression is critical to carry out accurate gene
      expression profiling. There is no 'universal' HKG having stable expression in all
      kinds of tissues under all experimental conditions. METHODS: The present study
      aims to identify most appropriate HKGs for gene expression analysis in
      glioblastoma (GBM) samples. Based on literature survey, six most commonly used
      HKGs that are invariant in GBM were chosen. We performed qPCR using RNA from
      formalin fixed paraffin embedded GBM samples and normal brain samples to
      investigate the expression pattern of HPRT, GAPDH, TBP, B2M, B2M, RPL13A, and
      RN18S1 with different abundance. A simple Deltacycle threshold approach was
      employed to calculate the fold change. RESULTS: Our study shows that the
      expression of RPL13A and TBP were found to be most stable across all the samples
      and are thus suitable for gene expression analysis in human GBM. Except for TBP,
      none of the other conventionally used HKGs in GBM studies e.g., HPRT and GAPDH
      were found to be suitable as they showed variation in RNA expression. CONCLUSION:
      Validation of HKGs is therefore immensely specific for a particular experimental
      setup and is crucial in assessing any new setup.

PMID- 25977904
TI  - A case of benign meningioma presented with subdural hemorrhage.
AB  - Meningiomas are the most common benign intracranial tumors and make up 13-26% of
      all primary intracranial tumors. Clinical presentation of hemorrhage is rare in
      these tumors occurring in approximately 1.3% of cases and subdural hemorrhages
      are even more uncommon. The mechanism of hemorrhage is still unclear and may vary
      according to histologic type, location and the type of hemorrhage. We experienced
      a case of 61-year-old woman with a benign meningioma presenting as a subdural
      hemorrhage. She developed sudden onset of headache right after aggressively
      coughing. Her headache persisted for a week before she was admitted to the
      emergency room of National Cancer Center. She had a past medical history of
      ovarian cancer which had been treated and was allegedly recurrence-free for 2
      years. At the time of admission, a headache was the only symptom and imaging
      studies showed a right frontal hemorrhagic subdural mass lesion accompanying an
      ipsilateral subdural hematoma. Elective surgery was performed and intraoperative
      findings revealed the hallmark characteristics of a meningioma with mixed stage
      diffuse subdural hematoma. Permanent pathology result determined it was a
      conventional meningioma (World Health Organization grade I). From this case, we
      discuss the rare presentation of subdural hemorrhage in meningioma and related
      points by reviewing the literature of previous studies. 

PMID- 25977905
TI  - Primary diffuse leptomeningeal gliosarcomatosis.
AB  - Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition with a
      fatal outcome, characterized by diffuse infiltration of the leptomeninges by
      neoplastic glial cells without evidence of primary tumor in the brain or spinal
      cord parenchyma. In particular, PDLG histologically diagnosed as gliosarcoma is
      extremely rare, with only 2 cases reported to date. We report a case of primary
      diffuse leptomeningeal gliosarcomatosis. A 68-year-old man presented with fever,
      chilling, headache, and a brief episode of mental deterioration. Initial T1
      weighted post-contrast brain magnetic resonance imaging (MRI) showed diffuse
      leptomeningeal enhancement without a definite intraparenchymal lesion. Based on
      clinical and imaging findings, antiviral treatment was initiated. Despite the
      treatment, the patient's neurologic symptoms and mental status progressively
      deteriorated and follow-up MRI showed rapid progression of the disease. A
      meningeal biopsy revealed gliosarcoma and was conclusive for the diagnosis of
      primary diffuse leptomeningeal gliosarcomatosis. We suggest the inclusion of PDLG
      in the potential differential diagnosis of patients who present with nonspecific
      neurologic symptoms in the presence of leptomeningeal involvement on MRI. 

PMID- 25977906
TI  - Thrombosed large middle cerebral artery aneurysm mimicking an intra-axial brain
      tumor: case report and review of literature.
AB  - This case report presents a fully thrombosed large aneurysm of middle cerebral
      artery mimicking an intra-axial brain tumor in a 54-year-old male patient. A
      small mass like lesion was found incidentally in right frontal area. Brain
      magnetic resonance image showed dark signal intensity on T2-weighted images and
      peripheral high signal intensity on T1-weighted images with peripheral rim
      enhancement. We considered intra-axial tumors such as glioma or metastatic tumor
      as a differential diagnosis. The lesion was approached transcortically, and
      intraoperatively, the lesion was found to be a large thrombosed aneurysm
      originating from the lateral lenticulostriate artery of right middle cerebral
      artery. One vascular clip was applied at the parent artery, and the thrombosed
      aneurysm was totally removed. There have been many reports of other intracranial
      lesions wrongly diagnosed as intracranial neoplasms. And thrombosed aneurysms
      mimicking intracranial neoplasm have been reported in 4 cases previously.
      According to those case reports, there were no efficient imaging tools to
      differentiate between these thrombosed aneurysms and intracranial neoplasms. We
      reviewed those reports and considered about the efficient method to diagnosed
      accurately before surgery. To sum up, when a patient presents with an
      intracranial lesion lying on the course of major or distal cerebral arteries, the
      surgeon should have thrombosed aneurysm in mind as one of the differential
      diagnosis and be prepared when surgically treating such lesions. 

PMID- 25977902
TI  - Modern brain tumor imaging.
AB  - The imaging and clinical management of patients with brain tumor continue to
      evolve over time and now heavily rely on physiologic imaging in addition to high
      resolution structural imaging. Imaging remains a powerful noninvasive tool to
      positively impact the management of patients with brain tumor. This article
      provides an overview of the current state-of-the art clinical brain tumor
      imaging. In this review, we discuss general magnetic resonance (MR) imaging
      methods and their application to the diagnosis of, treatment planning and
      navigation, and disease monitoring in patients with brain tumor. We review the
      strengths, limitations, and pitfalls of structural imaging, diffusion-weighted
      imaging techniques, MR spectroscopy, perfusion imaging, positron emission
      tomography/MR, and functional imaging. Overall this review provides a basis for
      understudying the role of modern imaging in the care of brain tumor patients. 

PMID- 25977907
TI  - The clinical characteristics of subependymal giant cell astrocytoma: five cases.
AB  - In this study, we reviewed the clinical characteristics of five cases of
      subependymal giant cell astrocytoma (SEGA) at our hospital between May 1997 and
      July 2012. The median age was 18 years old (range, 8 to 26). The clinical
      symptoms were presented as seizure in two patients and headache in three
      patients. All the tumors were located near the foramen of Monro. The median size
      of the tumors was 2.5 cm (range, 1.9-4.0). Two patients showed the solitary
      lesion, and three had subependymal nodules and cortical tubers. The median follow
      up duration was 7.4 years (range, 2.0-14.3). Three patients were associated with
      the tuberous sclerosis complex (TSC). Four patients showed the SEGA at the first
      presentation and one patient experienced the 1.9 cm-sized growing mass during 7.7
      years follow-up after the diagnosis of the TSC. The mass was totally removed in
      four patients and subtotally in one. Postoperatively, one patient took the
      medication for the seizure, which was controllable. The subtotally removed mass
      showed the recurrence postoperative 4.1 years later, and the recurred mass was
      stable for 4.5 years after the recurrence. The clinical follow-up study of the
      SEGA showed an indolent behavior before and after the surgery. 

PMID- 25977908
TI  - Concomitant Subdural Hemorrhage and Intracerebral Hemorrhage due to Brain
      Metastasis of the Hepatocellular Carcinoma.
AB  - Hemorrhagic metastatic brain tumors of hepatocellular carcinoma (HCC) are rare
      and have been mostly presented as intracranial hemorrhage (ICH). A 51-year-old
      male patient presented with sudden altered level of consciousness. He suffered
      from HCC since 2010 and transarterial chemoembolization was performed three times
      for HCC. The brain computed tomography (CT) scans revealed subdural hematoma
      (SDH) in the right fronto-temporal area and 6.0*3.5 cm sized ICH in the right
      parieto-occipital lobe. Brain angiographic CT scans demonstrated that the
      hemorrhagic lesions did not include any enhancing lesions and vascular
      abnormalities. We undertook a decompressive craniectomy and evacuation of the
      acute SDH and ICH. During evacuation of ICH, the yellowish mass was observed in
      the cortical surface of the right occipital lobe. Pathological examination
      displayed the findings of metastatic brain tumor from HCC. Metastatic brain
      tumors should be considered in the differential diagnosis as a cause of
      spontaneous SDH with ICH. 

PMID- 25977909
TI  - An unusual variant of anlage tumor of pineal region in an infant.
AB  - A 9-month-old male child was brought with complaints of increasing head size for
      2 months, increasing lethargy and vomiting for the last 2 days. Radiology
      revealed a heterogeneously enhancing, globular lesion in the pineal region with
      hydrocephalus. Near total excision of the tumor was carried out. The
      histopathological examination of the lesion showed heterogenous elements in the
      form of mature neuroepithelial and ectomesenchymal tissue. The pathology and
      radiology of this unusual lesion is discussed with relevant review of literature.

PMID- 25977910
TI  - The olfactory groove schwannoma attached to the cribriform plate: a case report.
AB  - The olfactory groove schwannoma is a quite rare tumor. We report a case of a 49
      year-old woman with an olfactory groove schwannoma attached to the cribriform
      plate without olfactory dysfunction. She had no specific neurological symptoms
      other than a headache, and resection of the tumor showed it to be a schwannoma.
      About 19 months after the operation, a follow-up MRI showed no evidence of tumor
      recurrence. Surgical resection through subfrontal approach could be one of the
      curative modality in managing an olfactory groove schwannoma. An olfactory groove
      schwannoma should be considered in the differential diagnosis of anterior skull
      base tumors. 

PMID- 25977911
TI  - Granular cell tumor in the pituitary stalk: a case report.
AB  - Granular cell tumors (GCTs) have been reported in various tissues, especially the
      skin and subcutaneous soft tissue of the head and neck. We report a 60-year-old
      man who presented with intermittent headache and dizziness for 3 months, but no
      other neurological symptoms. Magnetic resonance imaging (MRI) showed the presence
      of a mass in the pituitary stalk, and contrast-enhanced MRI showed nodular
      enhancement in this region. The lesion was completely excised microscopically via
      a frontotemporal (pterional) approach. On pathological examination, a final
      diagnosis of a typical GCT was made. 

PMID- 25977912
TI  - Rare locations of schwannomas: a few comments.

PMID- 25977913
TI  - RNA Degradation in Staphylococcus aureus: Diversity of Ribonucleases and Their
      Impact.
AB  - The regulation of RNA decay is now widely recognized as having a central role in
      bacterial adaption to environmental stress. Here we present an overview on the
      diversity of ribonucleases (RNases) and their impact at the posttranscriptional
      level in the human pathogen Staphylococcus aureus. RNases in prokaryotes have
      been mainly studied in the two model organisms Escherichia coli and Bacillus
      subtilis. Based on identified RNases in these two models, putative orthologs have
      been identified in S. aureus. The main staphylococcal RNases involved in the
      processing and degradation of the bulk RNA are (i) endonucleases RNase III and
      RNase Y and (ii) exonucleases RNase J1/J2 and PNPase, having 5' to 3' and 3' to
      5' activities, respectively. The diversity and potential roles of each RNase and
      of Hfq and RppH are discussed in the context of recent studies, some of which are
      based on next-generation sequencing technology. 

PMID- 25977915
TI  - Binding of citreoviridin to human serum albumin: multispectroscopic and molecular
      docking.
AB  - Citreoviridin (CIT), a mycotoxin produced by Penicillium citreonigrum, is a
      common contaminant of wide range of agriproducts and detrimental to human and
      animal health. In this study, the interaction of CIT with human serum albumin
      (HSA) is researched by steady-state fluorescence, ultraviolet-visible (UV-Vis)
      absorption, circular dichroism (CD) methods, and molecular modeling. The
      association constants, binding site numbers, and corresponding thermodynamic
      parameters are used to investigate the quenching mechanism. The alternations of
      HSA secondary structure in the presence of CIT are demonstrated with UV-Vis,
      synchronous fluorescence, and CD spectra. The molecular modeling results reveal
      that CIT can bind with hydrophobic pocket of HSA with hydrophobic and hydrogen
      bond force. Moreover, an apparent distance of 3.25 nm between Trp214 and CIT is
      obtained via fluorescence resonance energy transfer method.

PMID- 25977914
TI  - Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus.
AB  - Brain injury triggers a progressive inflammatory response supported by a dynamic
      astroglia-microglia interplay. We investigated the progressive chronic features
      of the astroglia-microglia cross talk in the perspective of neuronal effects in a
      rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA)
      injection triggered a process characterized within 38 days by atrophy, neuronal
      loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with
      the lesion progression. It presented a peak of tumor necrosis factor-alpha (TNF
      alpha) secretion at one day after the lesion, and a transient YM1 secretion
      within the first three days. Microglial glucocorticoid receptor expression
      increased up to day 5, before returning progressively to sham values. To further
      investigate the astroglia role in the microglia reaction, we performed
      concomitant transient astroglia ablation with L-alpha-aminoadipate and NMDA
      induced lesion. We observed a striking maintenance of neuronal death associated
      with enhanced microglial reaction and proliferation, increased YM1 concentration,
      and decreased TNF-alpha secretion and glucocorticoid receptor expression. S100B
      reactivity only increased after astroglia recovery. Our results argue for an
      initial neuroprotective microglial reaction, with a direct astroglial control of
      the microglial cytotoxic response. We propose the recovery of the astroglia
      microglia cross talk as a tissue priority conducted to ensure a proper cellular
      coordination that retails brain damage. 

PMID- 25977916
TI  - Intrinsic immunomodulatory effects of low-digestible carbohydrates selectively
      extend their anti-inflammatory prebiotic potentials.
AB  - The beneficial effects of carbohydrate-derived fibers are mainly attributed to
      modulation of the microbiota, increased colonic fermentation, and the production
      of short-chain fatty acids. We studied the direct immune responses to alimentary
      fibers in in vitro and in vivo models. Firstly, we evaluated the immunomodulation
      induced by nine different types of low-digestible fibers on human peripheral
      blood mononuclear cells. None of the fibers tested induced cytokine production in
      baseline conditions. However, only one from all fibers almost completely
      inhibited the production of anti- and proinflammatory cytokines induced by
      bacteria. Secondly, the impact of short- (five days) and long-term (three weeks)
      oral treatments with selected fibers was assessed in the trinitrobenzene-sulfonic
      acid colitis model in mice. The immunosuppressive fiber significantly reduced
      levels of inflammatory markers over both treatment periods, whereas a
      nonimmunomodulatory fiber had no effect. The two fibers did not differ in terms
      of the observed fermentation products and colonic microbiota after three weeks of
      treatment, suggesting that the anti-inflammatory action was not related to
      prebiotic properties. Hence, we observed a direct effect of a specific fiber on
      the murine immune system. This intrinsic, fiber-dependent immunomodulatory
      potential may extend prebiotic-mediated protection in inflammatory bowel disease.

PMID- 25977917
TI  - Functional genomics, genetics, and bioinformatics.

PMID- 25977919
TI  - Correlation between the Pharyngeal Airway Space and Head Posture after Surgery
      for Mandibular Prognathism.
AB  - PURPOSE: The aim of this study was to determine the correlation between the
      pharyngeal airway space and head posture after mandibular setback surgery for
      mandibular prognathism. MATERIALS AND METHODS: Serial lateral cephalograms of 37
      patients with mandibular prognathism who underwent intraoral vertical ramus
      osteotomy (IVRO) were evaluated before (T1) and immediately (T2), between 6 weeks
      and 3 months (T3), and more than 1 year (T4) after surgery. Paired t-tests and
      Pearson's correlation analysis were used to evaluate the postoperative changes in
      all cephalometric parameters, including the mandible, hyoid, head posture
      (craniocervical angle), and pharyngeal airway space. RESULTS: The mandible and
      hyoid were set back by 12.8 mm and 4.9 mm, respectively, at T2. Furthermore, the
      hyoid showed significant inferior movement of 10.7 mm, with an 8 mm increase in
      the tongue depth. The upper oropharyngeal airway (UOP) shortened by 4.1 mm, the
      lower oropharyngeal airway (LOP) by 1.7 mm, and the laryngopharyngeal airway by 2
      mm. The craniocervical angle showed a significant increase of 2.8 degrees . UOP
      and LOP showed a significant correlation with the craniocervical angle at T2 and
      T4. CONCLUSIONS: Our findings conclude that the oropharyngeal airway space is
      significantly decreased and correlated with a change in the head posture after
      mandibular setback surgery.

PMID- 25977918
TI  - Benchtop technologies for circulating tumor cells separation based on biophysical
      properties.
AB  - Circulating tumor cells (CTCs) are tumor cells that have detached from primary
      tumor site and are transported via the circulation system. The importance of CTCs
      as prognostic biomarker is leveraged when multiple studies found that patient
      with cutoff of 5 CTCs per 7.5 mL blood has poor survival rate. Despite its
      clinical relevance, the isolation and characterization of CTCs can be quite
      challenging due to their large morphological variability and the rare presence of
      CTCs within the blood. Numerous methods have been employed and discussed in the
      literature for CTCs separation. In this paper, we will focus on label free CTCs
      isolation methods, in which the biophysical and biomechanical properties of cells
      (e.g., size, deformability, and electricity) are exploited for CTCs detection. To
      assess the present state of various isolation methods, key performance metrics
      such as capture efficiency, cell viability, and throughput will be reported.
      Finally, we discuss the challenges and future perspectives of CTC isolation
      technologies.

PMID- 25977920
TI  - Molecular PET Imaging of Cyclophosphamide Induced Apoptosis with 18F-ML-8.
AB  - In this paper, a novel small-molecular apoptotic PET imaging probe, (18)F-ML-8
      with a malonate motif structure, is presented and discussed. After study, the
      small tracer that belongs to a member of ApoSense family is proved to be capable
      of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The
      experimental result is further confirmed by in vitro cell binding assays and
      TUNEL staining assay. As a result, (18)F-ML-8 could be used for noninvasive
      visualization of apoptosis induced by antitumor chemotherapy. 

PMID- 25977923
TI  - High variability of Fabry disease manifestations in an extended Italian family.
AB  - Fabry disease (FD) is an inherited metabolic disorder caused by partial or full
      inactivation of the lysosomal hydrolase alpha-galactosidase A (alpha-GAL). The
      impairment of alpha-GAL results in the accumulation of undegraded
      glycosphingolipids in lysosomes and subsequent cell and microvascular
      dysfunctions. This study reports the clinical, biochemical, and molecular
      characterization of 15 members of the same family. Eight members showed the
      exonic mutation M51I in the GLA gene, a disease-causing mutation associated with
      the atypical phenotype. The clinical history of this family highlights a wide
      phenotypic variability, in terms of involved organs and severity. The phenotypic
      variability of two male patients is not related to differences in alpha-GAL
      enzymatic activity: though both have no enzymatic activity, the youngest shows
      severe symptoms, while the eldest is asymptomatic. It is noticeable that for two
      female patients with the M51I mutation the initial clinical diagnosis was
      different from FD. One of them was diagnosed with Familial Mediterranean Fever,
      the other with Multiple Sclerosis. Overall, this study confirms that the extreme
      variability of the clinical manifestations of FD is not entirely attributable to
      different mutations in the GLA gene and emphasizes the need to consider other
      factors or mechanisms involved in the pathogenesis of Fabry Disease. 

PMID- 25977922
TI  - Anti-Lung Cancer Activity of the Curcumin Analog JZ534 In Vitro.
AB  - This study investigated the anticancer effect of the curcumin analog JZ534 on
      lung cancer cell lines H460, A549, H1975, and HCC827. The antiproliferation
      effect of JZ534 was measured through the methylthiazoletetrazolium assay, and
      cell colony formation was observed. Cell cycle and apoptosis were determined by
      flow cytometry, and the preliminary mechanism was studied by Western blot.
      Results showed that JZ534 significantly inhibited the vitality and colony
      formation of lung cancer cells. JZ534 induced the G2/M cell cycle arrest of the
      cancer cells and suppressed the expression of cycle-related proteins, including
      cyclin B1 and Cdc2. Meanwhile, JZ534 induced cell apoptosis and upregulated the
      expression of apoptosis-related proteins, including cleaved caspase-3, Bax, and
      p53. At the same dose, JZ534 showed better antitumor activity than curcumin.
      These results suggest that JZ534 exhibits excellent anti-lung cancer activity by
      inhibiting the growth and inducing the apoptosis of lung cancer cells. Therefore,
      JZ534 is a promising lead compound for cancer treatment. 

PMID- 25977921
TI  - Ca2+ signaling in cytoskeletal reorganization, cell migration, and cancer
      metastasis.
AB  - Proper control of Ca(2+) signaling is mandatory for effective cell migration,
      which is critical for embryonic development, wound healing, and cancer
      metastasis. However, how Ca(2+) coordinates structural components and signaling
      molecules for proper cell motility had remained elusive. With the advance of
      fluorescent live-cell Ca(2+) imaging in recent years, we gradually understand how
      Ca(2+) is regulated spatially and temporally in migrating cells, driving
      polarization, protrusion, retraction, and adhesion at the right place and right
      time. Here we give an overview about how cells create local Ca(2+) pulses near
      the leading edge, maintain cytosolic Ca(2+) gradient from back to front, and
      restore Ca(2+) depletion for persistent cell motility. Differential roles of
      Ca(2+) in regulating various effectors and the interaction of roles of Ca(2+)
      signaling with other pathways during migration are also discussed. Such
      information might suggest a new direction to control cancer metastasis by
      manipulating Ca(2+) and its associating signaling molecules in a judicious
      manner. 

PMID- 25977924
TI  - Functional Polymorphisms in COX-2 Gene Are Correlated with the Risk of Oral
      Cancer.
AB  - BACKGROUND: This meta-analysis investigated the association between functional
      COX-2 gene polymorphisms and the risk of oral cancer. METHODS: Several electronic
      databases were searched for published studies using combinations of keywords
      related to COX-2 gene polymorphisms and oral cancer. After selection of relevant
      studies, following strict inclusion and exclusion criteria, data was performed
      using STATA 12.0 software. RESULTS: We retrieved 83 studies from database search
      using specific search terms. After multiple rounds of selection and elimination,
      7 studies were finally identified as suitable to be included in our present meta
      analysis, based on their relevance and data integrity. These 7 studies contained
      a combined total of 2,296 oral cancer patients and 3,647 healthy controls. Our
      findings demonstrated that +837 T > C (rs5275) polymorphism in COX-2 showed
      statistically significant differences in gene frequencies in case and control
      groups in allele model and dominant model. Similar results were obtained with COX
      2 gene polymorphism 765 G > C (rs20417). On the other hand, 1195 A > G (rs689466)
      polymorphism in COX-2 did not confer susceptibility to oral cancers. CONCLUSION:
      Based on our results, COX-2 gene polymorphisms, +837 T > C (rs5275) and -765G > C
      (rs20417), showed clear links with oral cancer susceptibility, and the 1195A > G
      (rs689466) polymorphism did not show such a correlation.

PMID- 25977925
TI  - How do families of children with Down syndrome perceive speech intelligibility in
      Turkey?
AB  - Childhood verbal apraxia has not been identified or treated sufficiently in
      children with Down syndrome but recent research has documented that symptoms of
      childhood verbal apraxia can be found in children with Down syndrome. But, it is
      not routinely diagnosed in this population. There is neither an assessment tool
      in Turkish nor any research on childhood verbal apraxia although there is a
      demand not only for children with Down syndrome but also for normally developing
      children. The study examined if it was possible to determine oral-motor
      difficulties and childhood verbal apraxia features in children with Down syndrome
      through a survey. The survey was a parental report measure. There were 329
      surveys received. Results indicated that only 5.6% of children with Down syndrome
      were diagnosed with apraxia, even though many of the subject children displayed
      clinical features of childhood verbal apraxia. The most frequently reported
      symptoms of childhood verbal apraxia in literature were displayed by the children
      with Down syndrome in the study. Parents could identify childhood verbal apraxia
      symptoms using parent survey. This finding suggests that the survey can be
      developed that could serve as a screening tool for a possible childhood verbal
      apraxia diagnosis in Turkey. 

PMID- 25977926
TI  - Implications of Green Tea and Its Constituents in the Prevention of Cancer via
      the Modulation of Cell Signalling Pathway.
AB  - Green tea is commonly used as a beverage worldwide, especially in China, Japan,
      Morocco, and Saudi Arabia. Green tea and its constituents have been considered
      very effective in the prevention and treatment of various diseases. It contains a
      variety of catechins, which show a pivotal role in the modulation of biological
      activities and also act as chemopreventive agents. Earlier studies have confirmed
      that green tea and its chief constituent epigallocatechin gallate (EGCG) have a
      potential role in the management of cancer through the modulation of cell
      signaling pathways. In this review, we focused on the beneficial effects of green
      tea and its constituents in the cancer prevention and treatment and its impact on
      modulation of molecular pathways. 

PMID- 25977927
TI  - Biomaterials for pelvic floor reconstructive surgery: how can we do better?
AB  - Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major
      health issues that detrimentally impact the quality of life of millions of women
      worldwide. Surgical repair is an effective and durable treatment for both
      conditions. Over the past two decades there has been a trend to enforce or
      reinforce repairs with synthetic and biological materials. The determinants of
      surgical outcome are many, encompassing the physical and mechanical properties of
      the material used, and individual immune responses, as well surgical and
      constitutional factors. Of the current biomaterials in use none represents an
      ideal. Biomaterials that induce limited inflammatory response followed by
      constructive remodelling appear to have more long term success than biomaterials
      that induce chronic inflammation, fibrosis and encapsulation. In this review we
      draw upon published animal and human studies to characterize the changes
      biomaterials undergo after implantation and the typical host responses, placing
      these in the context of clinical outcomes. 

PMID- 25977928
TI  - Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic
      Polyneuropathy in Mice.
AB  - BACKGROUND: Although numerous reports addressing pathological involvements of
      diabetic polyneuropathy have been conducted, a universally effective treatment of
      diabetic polyneuropathy has not yet been established. Recently, regenerative
      medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell
      have been reported. However, the effectiveness of these cell transplantations was
      restricted because of their functional and numerical impairment in diabetic
      objects. Here, we investigated the efficacy of treatment for diabetic
      polyneuropathy using angioblast-like cells derived from mouse embryonic stem
      cells. METHODS AND RESULTS: Angioblast-like cells were obtained from mouse
      embryonic stem cells and transplantation of these cells improved several
      physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve
      conduction velocities, and reduced blood flow in sciatic nerve and plantar skin.
      Furthermore, pathologically, the capillary number to muscle fiber ratios were
      increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve
      fiber densities were ameliorated in transplanted plantar skin. Transplanted cells
      maintained their viabilities and differentiated to endothelial cells and smooth
      muscle cells around the injection sites. Moreover, several transplanted cells
      constructed chimeric blood vessels with recipient cells. CONCLUSIONS: These
      results suggest that transplantation of angioblast like cells induced from
      embryonic stem cells appears to be a novel therapeutic strategy for diabetic
      polyneuropathy.

PMID- 25977929
TI  - The impact of abnormal glucose tolerance and obesity on fetal growth.
AB  - OBJECTIVE: Factors linked with insulin resistance were examined for their
      association with large-for-gestational-age (LGA) infant birth weight and
      gestational diabetes. STUDY DESIGN: Data came from a longitudinal cohort study of
      2,305 subjects without overt diabetes, analyzed using multinomial logistic and
      linear regression. RESULTS: High maternal BMI (OR = 1.53 (1.11, 2.12)), height
      (1.98 (1.62, 2.42)), antidepressant use (1.71 (1.20, 2.44)), pregnancy weight
      gain exceeding 40 pounds (1.79 (1.25, 2.57)), and high blood sugar (2.68, (1.53,
      5.27)) were all positively associated with LGA birth. Strikingly, the difference
      in risk from diagnosed and treated gestational diabetes compared to women with a
      single abnormal glucose tolerance test (but no diagnosis of gestational diabetes)
      was significant (OR = 0.65, p = 0.12 versus OR = 2.84, p < 0.01). When
      weight/length ratio was used instead, different factors were found to be
      significant. BMI and pregnancy weight-gain were found to influence the
      development of gestational diabetes, through an additive interaction.
      CONCLUSIONS: High prepregnancy BM, height, antidepressant use, pregnancy weight
      gain exceeding 40 pounds, and high blood sugar were associated with LGA birth,
      but not necessarily infant weight/length ratio. An additive interaction between
      BMI and pregnancy weight-gain influenced gestational diabetes development.

PMID- 25977930
TI  - Genetic Associations of PPARGC1A with Type 2 Diabetes: Differences among
      Populations with African Origins.
AB  - The aim of this study was to assess the differences in correlation of PPARGC1A
      polymorphisms with type 2 diabetes (T2D) risk in adults of African origins:
      African Americans and Haitian Americans. The case-control study consisted of >30
      years old, self-identified Haitian Americans (n = 110 cases and n = 116 controls)
      and African Americans (n = 124 cases and n = 122 controls) living in South
      Florida with and without T2D. Adjusted logistic regression indicated that both
      SNP rs7656250 (OR = 0.22, P = 0.005) and rs4235308 (OR = 0.42, P = 0.026) showed
      protective association with T2D in Haitian Americans. In African Americans,
      however, rs4235308 showed significant risk association with T2D (OR = 2.53, P =
      0.028). After stratification with sex, in Haitian Americans, both rs4235308 (OR =
      0.38, P = 0.026) and rs7656250 (OR = 0.23, P = 0.006) showed protective
      association with T2D in females whereas in African American males rs7656250 had
      statistically significant protective effect on T2D (OR = 0.37, P = 0.043). The
      trends observed for genetic association of PPARGC1A SNPs, rs4235308, and
      rs7656250 for T2D between Haitian Americans and African Americans point out
      differences in Black race and warrant replicative study with larger sample size. 

PMID- 25977933
TI  - Erratum: P2Y12 expression and function in alternatively activated human
      microglia.
AB  - [This corrects the article on p. e80 in vol. 2, PMID: 25821842.]. 

PMID- 25977932
TI  - B lymphocytes in neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that
      predominantly affects the spinal cord and optic nerves. A majority (approximately
      75%) of patients with NMO are seropositive for autoantibodies against the
      astrocyte water channel aquaporin-4 (AQP4). These autoantibodies are
      predominantly IgG1, and considerable evidence supports their pathogenicity,
      presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury
      and inflammation. Convergent clinical and laboratory-based investigations have
      indicated that B cells play a fundamental role in NMO immunopathology. Multiple
      mechanisms have been hypothesized: AQP4 autoantibody production, enhanced
      proinflammatory B cell and plasmablast activity, aberrant B cell tolerance
      checkpoints, diminished B cell regulatory function, and loss of B cell anergy.
      Accordingly, many current off-label therapies for NMO deplete B cells or modulate
      their activity. Understanding the role and mechanisms whereby B cells contribute
      to initiation, maintenance, and propagation of disease activity is important to
      advancing our understanding of NMO pathogenesis and developing effective disease
      specific therapies. 

PMID- 25977931
TI  - Crosstalk between the unfolded protein response and NF-kappaB-mediated
      inflammation in the progression of chronic kidney disease.
AB  - The chronic inflammatory response is emerging as an important therapeutic target
      in progressive chronic kidney disease. A key transcription factor in the
      induction of chronic inflammation is NF-kappaB. Recent studies have demonstrated
      that sustained activation of the unfolded protein response (UPR) can initiate
      this NF-kappaB signaling phenomenon and thereby induce chronic kidney disease
      progression. A key factor influencing chronic kidney disease progression is
      proteinuria and this condition has now been demonstrated to induce sustained UPR
      activation. This review details the crosstalk between the UPR and NF-kappaB
      pathways as pertinent to chronic kidney disease. We present potential tools to
      study this phenomenon as well as potential therapeutics that are emerging to
      regulate the UPR. These therapeutics may prevent inflammation specifically
      induced in the kidney due to proteinuria-induced sustained UPR activation. 

PMID- 25977934
TI  - alphabeta T-cell receptors from multiple sclerosis brain lesions show MAIT cell
      related features.
AB  - OBJECTIVES: To characterize phenotypes of T cells that accumulated in multiple
      sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire
      of T-cell subsets to peripheral blood, and to identify paired alpha and beta
      chains from single CD8(+) T cells from an index patient who we followed for 18
      years. METHODS: We combined immunohistochemistry, laser microdissection, and
      single-cell multiplex PCR to characterize T-cell subtypes and identify paired
      TCRalpha and TCRbeta chains from individual brain-infiltrating T cells in frozen
      brain sections. The lesional and peripheral TCR repertoires were analyzed by
      pyrosequencing. RESULTS: We found that a TCR Vbeta1(+) T-cell population that was
      strikingly expanded in active brain lesions at clinical onset comprises several
      subclones expressing distinct yet closely related Valpha7.2(+) alpha chains,
      including a canonical Valpha7.2-Jalpha33 chain of mucosal-associated invariant T
      (MAIT) cells. Three other alpha chains bear striking similarities in their
      antigen-recognizing, hypervariable complementarity determining region 3.
      Longitudinal repertoire studies revealed that the TCR chains that were massively
      expanded in brain at onset persisted for several years in blood or CSF but
      subsequently disappeared except for the canonical Valpha7.2(+) MAIT cell and a
      few other TCR sequences that were still detectable in blood after 18 years.
      CONCLUSIONS: Our observation that a massively expanded TCR Vbeta1-Jbeta2.3 chain
      paired with distinct yet closely related canonical or atypical MAIT cell-related
      alpha chains strongly points to an antigen-driven process in early active MS
      brain lesions.

PMID- 25977935
TI  - Varicella-zoster virus encephalitis localized to the bilateral medial temporal
      lobes.

PMID- 25977936
TI  - Hippocampal volume and depressive symptoms are linked to serum IL-18 in
      schizophrenia.
AB  - OBJECTIVE: Since schizophrenia (SCZ) is often accompanied by hippocampal
      abnormalities and dysregulation of cytokine production, this study aimed to
      investigate the impact of the cytokine interleukin (IL)-18, whose biological
      system appears to be perturbed in SCZ, on brain structure and clinical severity
      in patients with chronic SCZ. METHODS: The serum levels of IL-18, including its
      free bioactive form (i.e., the cytokine fraction not bound to its specific
      endogenous inhibitor IL-18 binding protein), were evaluated in a case-control
      study involving 71 individuals with SCZ diagnosis and 29 healthy controls. All
      participants underwent brain MRI automatic evaluation for hippocampal volume
      estimation. The Positive and Negative Syndrome Scale (PANSS) was administered to
      measure severity of symptoms in patients with SCZ. RESULTS: Lower amounts of free
      IL-18 were related to smaller hippocampal volume measures in patients with SCZ.
      Furthermore, in line with a possible neuroprotective effect of the cytokine,
      higher levels of free IL-18 corresponded to lower subscores of PANSS depression
      in patients with SCZ. CONCLUSIONS: These findings demonstrate that the levels of
      circulating bioactive IL-18 are related to both hippocampal volume and severity
      of psychopathologic symptoms in patients with SCZ, confirming the involvement of
      the cytokine in SCZ pathophysiology and suggesting hippocampal-dependent and
      neuroprotective functions of IL-18 in this clinical context.

PMID- 25977938
TI  - Improving Lowland Rice (O. sativa L. cv. MR219) Plant Growth Variables, Nutrients
      Uptake, and Nutrients Recovery Using Crude Humic Substances.
AB  - High cation exchange capacity and organic matter content of crude humic
      substances from compost could be exploited to reduce ammonia loss from urea and
      to as well improve rice growth and soil chemical properties for efficient
      nutrients utilization in lowland rice cultivation. Close-dynamic air flow system
      was used to determine the effects of crude humic substances on ammonia
      volatilization. A pot experiment was conducted to determine the effects of crude
      humic substances on rice plant growth, nutrients uptake, nutrients recovery, and
      soil chemical properties using an acid soil mixed with three rates of crude humic
      substances (20, 40, and 60 g pot(-1)). Standard procedures were used to evaluate
      rice plant dry matter production, nutrients uptake, nutrients recovery, and soil
      chemical properties. Application of crude humic substances increased ammonia
      volatilization. However, the lowest rate of crude humic substances (20 g pot(-1))
      significantly improved total dry matter, nutrients uptake, nutrients recovery,
      and soil nutrients availability compared with crude humic substances (40 and 60 g
      pot(-1)) and the normal fertilization. Apart from improving growth of rice
      plants, crude humic substances can be used to ameliorate acid soils in rice
      cultivation. The findings of this study are being validated in our ongoing field
      trials.

PMID- 25977937
TI  - Insulin resistance and skin diseases.
AB  - In medical practice, almost every clinician may encounter patients with skin
      disease. However, it is not always easy for physicians of all specialties to face
      the daily task of determining the nature and clinical implication of dermatologic
      manifestations. Are they confined to the skin, representing a pure dermatologic
      event? Or are they also markers of internal conditions relating to the patient's
      overall health? In this review, we will discuss the principal cutaneous
      conditions which have been linked to metabolic alterations. Particularly, since
      insulin has an important role in homeostasis and physiology of the skin, we will
      focus on the relationships between insulin resistance (IR) and skin diseases,
      analyzing strongly IR-associated conditions such as acanthosis nigricans, acne,
      and psoriasis, without neglecting emerging and potential scenarios as the ones
      represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism. 

PMID- 25977939
TI  - The next new target in leukemia: The embryonic stem cell gene SALL4.
AB  - The embryonic stem (ES) cell gene SALL4 has recently been identified as a new
      target for cancer therapy, including leukemia. SALL4 is expressed in ES cells and
      during embryonic development, but is absent in most adult tissues. It is,
      however, aberrantly expressed in various solid tumors and hematologic
      malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia
      (AML). Aberrant expression of SALL4 is frequently associated with a more
      aggressive cancer phenotype, which includes high-risk MDS and its progression to
      AML. SALL4 contributes to leukemogenesis through multiple pathways including the
      repression of PTEN and the activation of HOXA9 expression. Targeting the
      SALL4/PTEN pathway by blocking the protein-protein interaction of SALL4 and its
      associated epigenetic complex, nucleosome remodeling and deacetylase complex
      (NuRD), might be a novel approach to treating AML and holds great potential for
      the treatment of other SALL4-mediated oncogenic processes such as high-risk MDS
      and solid tumors.

PMID- 25977940
TI  - A Candida albicans CRISPR system permits genetic engineering of essential genes
      and gene families.
AB  - Candida albicans is a pathogenic yeast that causes mucosal and systematic
      infections with high mortality. The absence of facile molecular genetics has been
      a major impediment to analysis of pathogenesis. The lack of meiosis coupled with
      the absence of plasmids makes genetic engineering cumbersome, especially for
      essential functions and gene families. We describe a C. albicans CRISPR system
      that overcomes many of the obstacles to genetic engineering in this organism. The
      high frequency with which CRISPR-induced mutations can be directed to target
      genes enables easy isolation of homozygous gene knockouts, even without
      selection. Moreover, the system permits the creation of strains with mutations in
      multiple genes, gene families, and genes that encode essential functions. This
      CRISPR system is also effective in a fresh clinical isolate of undetermined
      ploidy. Our method transforms the ability to manipulate the genome of Candida and
      provides a new window into the biology of this pathogen.

PMID- 25977942
TI  - Rapid detection of cocaine, benzoylecgonine and methylecgonine in fingerprints
      using surface mass spectrometry.
AB  - Latent fingerprints provide a potential route to the secure, high throughput and
      non-invasive detection of drugs of abuse. In this study we show for the first
      time that the excreted metabolites of drugs of abuse can be detected in
      fingerprints using ambient mass spectrometry. Fingerprints and oral fluid were
      taken from patients attending a drug and alcohol treatment service. Gas
      chromatography mass spectrometry (GC-MS) was used to test the oral fluid of
      patients for the presence of cocaine and benzoylecgonine. The corresponding
      fingerprints were analysed using Desorption Electrospray Ionization (DESI) which
      operates under ambient conditions and Ion Mobility Tandem Mass Spectrometry
      Matrix Assisted Laser Desorption Ionization (MALDI-IMS-MS/MS) and Secondary Ion
      Mass Spectrometry (SIMS). The detection of cocaine, benzoylecgonine (BZE) and
      methylecgonine (EME) in latent fingerprints using both DESI and MALDI showed good
      correlation with oral fluid testing. The sensitivity of SIMS was found to be
      insufficient for this application. These results provide exciting opportunities
      for the use of fingerprints as a new sampling medium for secure, non-invasive
      drug detection. The mass spectrometry techniques used here offer a high level of
      selectivity and consume only a small area of a single fingerprint, allowing
      repeat and high throughput analyses of a single sample. 

PMID- 25977943
TI  - Graphene oxide nanocapsules within silanized hydrogels suitable for
      electrochemical pseudocapacitors.
AB  - Soft biocompatible gels comprised of rolled up graphene oxide nanocapsules within
      the pores of silanized hydrogels may be used as electrochemical pseudocapacitors
      with physiological glucose or KOH as a reducing agent, affording a material
      suitable for devices requiring pulses with characteristic time less than a
      second. 

PMID- 25977944
TI  - Photo-triggered fluorescent labelling of recombinant proteins in live cells.
AB  - A method to photo-chemically trigger fluorescent labelling of proteins in live
      cells is developed. The approach is based on photo-caged split-intein mediated
      conditional protein trans-splicing reaction and enabled background-free
      fluorescent labelling of target proteins with the necessary spatiotemporal
      control. 

PMID- 25977945
TI  - A new lithium-rich anti-spinel in Li-O-Br system.
AB  - In spinel-type materials currently known, the divalent anions are arranged in a
      closed-pack lattice and cations of various valences occupy some or all of the
      tetrahedral and octahedral sites. We report here the first discovery of an
      "electronically inverted" anti-spinel. The new material, crystallized in a defect
      spinel structure, was obtained from the dehydration of Li5Br(OH)4 under moderate
      pressure and temperature conditions. 

PMID- 25977946
TI  - Water-soluble plasmonic nanosensors with synthetic receptors for label-free
      detection of folic acid.
AB  - We describe an original approach to graft molecularly imprinted polymers around
      gold nanorods by combining the diazonium salt chemistry and the iniferter method.
      This chemical strategy enables fine control of the imprinting process at the
      nanometer scale and provides water-soluble plasmonic nanosensors. 

PMID- 25977941
TI  - A review of flux considerations for in vivo neurochemical measurements.
AB  - The mass transport or flux of neurochemicals in the brain and how this flux
      affects chemical measurements and their interpretation is reviewed. For all
      endogenous neurochemicals found in the brain, the flux of each of these
      neurochemicals exists between sources that produce them and the sites that
      consume them all within MUm distances. Principles of convective-diffusion are
      reviewed with a significant emphasis on the tortuous paths and discrete point
      sources and sinks. The fundamentals of the primary methods of detection,
      microelectrodes and microdialysis sampling of brain neurochemicals are included
      in the review. Special attention is paid to the change in the natural flux of the
      neurochemicals caused by implantation and consumption at microelectrodes and
      uptake by microdialysis. The detection of oxygen, nitric oxide, glucose, lactate,
      and glutamate, and catecholamines by both methods are examined and where possible
      the two techniques (electrochemical vs. microdialysis) are compared. Non-invasive
      imaging methods: magnetic resonance, isotopic fluorine MRI, electron paramagnetic
      resonance, and positron emission tomography are also used for different
      measurements of the above-mentioned solutes and these are briefly reviewed.
      Although more sophisticated, the imaging techniques are unable to track
      neurochemical flux on short time scales, and lack spatial resolution. Where
      possible, determinations of flux using imaging are compared to the more classical
      techniques of microdialysis and microelectrodes. 

PMID- 25977947
TI  - A general method for synthesizing enzyme-polymer conjugates in reverse emulsions
      using Pluronic as a reactive surfactant.
AB  - Using aldehyde-functionalized Pluronic as the reactive surfactant, enzyme
      Pluronic conjugates with sizes ranging from nanometers to micrometers were
      synthesized in reverse emulsions. Compared with the direct conjugation in aqueous
      solution, this method gave an increased conjugation efficiency and well
      controlled size of the conjugates. The versatility of this method was validated
      using horseradish peroxidase (HRP), Candida rugosa lipase (CRL) and Candida
      antarctica lipase B (CALB). The resulting enzyme-Pluronic conjugates showed
      greatly enhanced apparent activity compared to free enzymes in organic media. 

PMID- 25977948
TI  - Optical gain from polyfluorene keto defects in a liquid crystal mixture.
AB  - By means of confocal photoluminescence measurements and fs pump-probe
      spectroscopy, we observe the optical properties of phase separation in a mixture
      of polyfluorene and Liquid Crystals (LCs). The boundaries of LC-rich micro
      domains display a large polarized gain region from keto defects stemming from the
      single-chain nature of this defect. 

PMID- 25977949
TI  - Chemical decoration of CH3NH3PbI3 perovskites with graphene oxides for
      photodetector applications.
AB  - A facile in situ solution method was developed for chemical decoration of
      CH3NH3PbI3 perovskites with reduced graphene oxides (rGOs) to significantly
      improve the photodetector performance. Such CH3NH3PbI3/rGO molecular hybrids show
      a 6 times higher ON/OFF ratio and notably faster response speed than neat
      CH3NH3PbI3. 

PMID- 25977950
TI  - Improved method for synthesis of cysteine modified hyaluronic acid for in situ
      hydrogel formation.
AB  - We developed a new strategy for the functionalization of hyaluronic acid by
      chemical modification of its C-6 hydroxyl groups through an ether bond to obtain
      a cysteine-hyaluronic acid conjugate. This conjugate is suitable to prepare
      injectable and in situ formed hydrogels cross-linked by native chemical ligation
      and Michael addition under mild conditions. 

PMID- 25977951
TI  - Synthesis and characterization of cell-microenvironment-sensitive leakage-free
      gold-shell nanoparticles with the template of interlayer-crosslinked micelles.
AB  - Novel gold-shell nanoparticles (pH-GSNPs) are designed for the first time, which
      exhibit drug leakage-free behavior in a physiological environment, while
      achieving rapid drug release and remarkable aggregation for the nanogold
      interlayer of pH-GSNPs to shift their absorption to far-red and NIR as a
      photothermal agent in the intracellular microenvironment. 

PMID- 25977952
TI  - Copper(I)-catalyzed carbon-halogen bond-selective boryl substitution of alkyl
      halides bearing terminal alkene moieties.
AB  - The selective boryl substitution of alkyl halides bearing terminal C[double bond,
      length as m-dash]C double bonds has been achieved using a
      copper(i)/tricyclohexylphosphine or copper(i)/o-diphenylphosphinophenol catalyst.
      This reaction represents a useful complementary approach to conventional
      procedures for the hydroboration of C[double bond, length as m-dash]C double
      bonds or the borylative cyclization of alkyl halides bearing terminal alkenes. 

PMID- 25977953
TI  - Decarboxylative Reissert type trifluoro- and trichloro-methylation of
      (iso)quinoline derivatives in batch and continuous flow.
AB  - Two decarboxylative methods providing access to N-alkylated alpha
      trihalomethylated heterocyclic amines have been developed. A batch protocol in
      which methyl trifluoroacetate acts both as a methylating reagent and subsequently
      as a nucleophilic trifluoromethyl anion precursor upon its addition to
      (iso)quinoline derivatives. Next, a telescoped continuous flow process, forming
      the corresponding alpha-trichloromethylated heterocyclic amines, utilizing a
      similar decarboxylation of trichloroacetic acid, was developed and taken to scale
      up. 

PMID- 25977954
TI  - Direct electrochemiluminescence of gold nanoparticles bifunctionalized by luminol
      analogue-metal complexes in neutral and alkaline media.
AB  - Electrochemiluminescence of gold nanoparticles bifunctionalized by luminol
      analogue-metal complexes was studied for the first time. Strong direct
      electrochemiluminescence was observed in neutral and alkaline media without an
      additional coreactant. 

PMID- 25977956
TI  - In memoriam: Wolfgang Strabetaer (1941-2015).

PMID- 25977957
TI  - Visual computing challenges of advanced manufacturing and Industrie 4.0.

PMID- 25977955
TI  - A review of back-calculation techniques  and their potential to inform mitigation
      strategies with application to  non-transmissible acute infectious  diseases.
AB  - Back-calculation is a process whereby generally unobservable features of an event
      leading to a disease outbreak can be inferred either in real-time or shortly
      after the end of the outbreak. These features might include the time when persons
      were exposed and the source of the outbreak. Such inferences are important as
      they can help to guide the targeting of mitigation strategies and to evaluate the
      potential effectiveness of such strategies. This article reviews the process of
      back-calculation with a particular emphasis on more recent applications
      concerning deliberate and naturally occurring aerosolized releases. The
      techniques can be broadly split into two themes: the simpler temporal models and
      the more sophisticated spatio-temporal models. The former require input data in
      the form of cases' symptom onset times, whereas the latter require additional
      spatial information such as the cases' home and work locations. A key aspect in
      the back-calculation process is the incubation period distribution, which forms
      the initial topic for consideration. Links between atmospheric dispersion
      modelling, within-host dynamics and back-calculation are outlined in detail. An
      example of how back-calculation can inform mitigation strategies completes the
      review by providing improved estimates of the duration of antibiotic prophylaxis
      that would be required in the response to an inhalational anthrax outbreak.

PMID- 25977958
TI  - Isotropic microscale mechanical properties  of coral skeletons.
AB  - Scleractinian corals are a major source of biogenic calcium carbonate, yet the
      relationship between their skeletal microstructure and mechanical properties has
      been scarcely studied. In this work, the skeletons of two coral species:solitary
      Balanophyllia europaea and colonial Stylophora pistillata, were investigated by
      nanoindentation. The hardness HIT and Young's modulus E(IT) were determined from
      the analysis of several load-depth data on two perpendicular sections of the
      skeletons: longitudinal (parallel to the main growth axis) and transverse. Within
      the experimental and statistical uncertainty,the average values of the mechanical
      parameters are independent on the section's orientation. The hydration state of
      the skeletons did not affect the mechanical properties. The measured values, EIT
      in the 76-77 GPa range, and H(IT) in the 4.9-5.1 GPa range, are close to the ones
      expected for polycrystalline pure aragonite. Notably, a small difference in H(IT)
      is observed between the species. Different from corals, single-crystal aragonite
      and the nacreous layer of the seashell Atrina rigida exhibit clearly orientation
      dependent mechanical properties. The homogeneous and isotropic mechanical
      behaviour of the coral skeletons at the microscale is correlated with the
      microstructure,observed by electron microscopy and atomic force microscopy, and
      with the X-ray diffraction patterns of the longitudinal and transverse sections.

PMID- 25977959
TI  - Demic and cultural diffusion propagated  the Neolithic transition across
      different  regions of Europe.
AB  - The Neolithic transition is the shift from hunting-gathering into farming. About
      9000 years ago, the Neolithic transition began to spread from the Near East into
      Europe, until it reached Northern Europe about 5500 years ago. There are two main
      models of this spread. The demic model assumes that it was mainly due to the
      reproduction and dispersal of farmers. The cultural model assumes that European
      hunter-gatherers become farmers by acquiring domestic plants and animals, as well
      as knowledge, from neighbouring farmers. Here we use the dates of about 900
      archaeological sites to compute a speed map of the spread of the Neolithic
      transition in Europe. We compare the speed map to the speed ranges predicted by
      purely demic, demic-cultural and purely cultural models. The comparison indicates
      that the transition was cultural in Northern Europe, the Alpine region and west
      of the Black Sea. But demic diffusion was at work in other regions such as the
      Balkans and Central Europe. Our models can be applied to many other cultural
      traits. We also propose that genetic data could be gathered and used to measure
      the demic kernels of Early Neolithic populations. This would lead to an enormous
      advance in Neolithic spread modelling.

PMID- 25977960
TI  - A novel collagen gel-based measurement  technique for quantitation of cell 
      contraction force.
AB  - Cell contraction force plays an important role in wound healing,
      inflammation,angiogenesis and metastasis. This study describes a novel method to
      quantify single cell contraction force in vitro using human aortic adventitial
      fibroblasts embedded in a collagen gel. The technique is based on a depth sensing
      nano-indentation tester to measure the thickness and elasticity of collagen gels
      containing stimulated fibroblasts and a microscopy imaging system to estimate the
      gel area. In parallel, a simple theoretical model has been developed to calculate
      cell contraction force based on the measured parameters. Histamine (100 mM) was
      used to stimulate fibroblast contraction while the myosin light chain kinase
      inhibitor ML-7 (25 mM) was used to inhibit cell contraction. The collagen matrix
      used in the model provides a physiological environment for fibroblast contraction
      studies. Measurement of changes in collagen gel elasticity and thickness arising
      from histamine treatments provides a novel convenient technique to measure cell
      contraction force within a collagen matrix. This study demonstrates that
      histamine can elicit a significant increase in contraction force of fibroblasts
      embedded in collagen,while the Young's modulus of the gel decreases due to the
      gel degradation.

PMID- 25977962
TI  - Childlessness and investment in nieces, nephews, aunts and uncles in Finland.
AB  - Kin selection theory predicts that individuals may increase their inclusive
      fitness by investing in their genetically related kin. In addition, according to
      the reproductive value hypothesis, individuals may increase their fitness more by
      investing in their kin in descending rather than ascending order. The present
      study uses the Generational Transmissions in Finland data collected in 2012 (n
      1/4 601 women) and analyses whether childless younger women invest more in their
      kin than younger women with children. The study finds that childless women are
      more likely than mothers to invest in their nieces and nephews but not their
      aunts and uncles. Thus the results are in line with the reproductive value
      prediction.

PMID- 25977961
TI  - Modelling the emergence of polarity  patterns for the intercellular transport  of
      auxin in plants.
AB  - The hormone auxin is actively transported throughout plants via protein
      machineries including the dedicated transporter known as PIN. The associated
      transport is ordered with nearby cells driving auxin flux in similar directions.
      Here, we provide a model of both the auxin transport and of the dynamics of
      cellular polarization based on flux sensing. Our main findings are: (i)
      spontaneous intracellular PIN polarization arises if PIN recycling dynamics are
      sufficiently nonlinear, (ii) there is no need for an auxin concentration gradient
      and (iii) ordered multi-cellular patterns of PIN polarization are favoured by
      molecular noise.

PMID- 25977963
TI  - The trend in age at menarche in Indonesia: birth cohorts 1944-1988.
AB  - Employing the Indonesian Family Life Survey, this paper depicts the trend in age
      at menarche in Indonesia for women born in 1944-1988. Mean age at menarche
      decreased from 14.39 years for birth year 1944 to 13.18 years for birth year
      1988. Subsequently, this trend is related to the improvement in material
      conditions, measured by GDP per capita in childhood. The OLS results indicate
      that this decrease is largely explained by the improvement in material
      conditions. If age at menarche is considered an indicator of biological standard
      of living, these results suggest that the improvement in material conditions
      during the period converted to an improvement in biological standard of living.

PMID- 25977964
TI  - Adapting to disaster? A commentary on Hamamatsu et al. (2014).

PMID- 25977965
TI  - Secondary sex ratio and marriage after disaster: a reply to O'Donnell and Behie.

PMID- 25977966
TI  - Adapting to disaster? A commentary on Hamamatsu et al. (2014)--a brief reply.

PMID- 25977967
TI  - Independent films communicating science at Sundance 2014.

PMID- 25977968
TI  - In memoriam: Henry B. Betts, MD, friend and mentor.

PMID- 25977969
TI  - Retraction notice to "Expression of a truncated Hmga1b gene induces gigantism,
      lipomatosis and B-cell lymphomas in mice" [Eur J Cancer 47 (2011) 470-478].

PMID- 25977970
TI  - Adjunct teaching: For love of the lecture.

PMID- 25977971
TI  - Retraction notice to erratum to "Modelling subcortical bone in finite element
      analyses: a validation and sensitivity study in the macaque mandible" [J.
      Biomech. 43 (2010) 2867].

PMID- 25977972
TI  - Retraction notice to "Modelling subcortical bone in finite element analyses: a
      validation and sensitivity study in the macaque mandible" [J. Biomech. 43 (2010)
      1603-1611].

PMID- 25977973
TI  - In Memoriam Dr. Colin Ogilvie Gill (1943-2014).

PMID- 25977974
TI  - [Stem cell renewal and cancer epidemiology - about a paper published in Science
      by Tomasetti and Vogelstein].

PMID- 25977975
TI  - Synthesis and higher-order structure of linear dendrimeric assemblies.
AB  - A series of linear covalent assemblies of dendrimers with conjugated backbones
      were synthesized by means of an iterative divergent and convergent method in
      which copper-catalyzed acetylene-azide cycloaddition reactions were used to form
      flexible linkages. UV-vis and fluorescence spectra indicate that dendrimeric
      assemblies have a strong propensity to adopt folded conformations in which
      conjugated backbones adopt planar conformations. The folded conformation is
      stabilized by strong attractive van der Waals and dipole-dipole interactions
      between the dendrimers. 

PMID- 25977976
TI  - Temperature-Induced Assembly of Monodisperse, Covalently Cross-Linked, and
      Degradable Poly(N-isopropylacrylamide) Microgels Based on Oligomeric Precursors.
AB  - A simple, rapid, solvent-free, and scalable thermally driven self-assembly
      approach is described to produce monodisperse, covalently cross-linked, and
      degradable poly(N-isopropylacrylamide) (PNIPAM) microgels based on mixing
      hydrazide (PNIPAM-Hzd) and aldehyde (PNIPAM-Ald) functionalized PNIPAM
      precursors. Preheating of a seed PNIPAM-Hzd solution above its phase transition
      temperature produces nanoaggregates that are subsequently stabilized and cross
      linked by the addition of PNIPAM-Ald. The ratio of PNIPAM-Hzd:PNIPAM-Ald used to
      prepare the microgels, the time between PNIPAM-Ald addition and cooling, the
      temperature to which the PNIPAM-Hzd polymer solution is preheated, and the
      concentration of PNIPAM-Hzd in the initial seed solution can all be used to
      control the size of the resulting microgels. The microgels exhibit similar
      thermal phase transition behavior to conventional precipitation-based microgels
      but are fully degradable into oligomeric precursor polymers. The microgels can
      also be lyophilized and redispersed without any change in colloidal stability or
      particle size and exhibit no significant cytotoxicity in vitro. We anticipate
      that microgels fabricated using this approach may facilitate translation of the
      attractive properties of such microgels in vivo without the concerns regarding
      microgel clearance that exist with other PNIPAM-based microgels. 

PMID- 25977977
TI  - [Tl(III)(dota)](-): An Extraordinarily Robust Macrocyclic Complex.
AB  - The X-ray structure of {C(NH2)3}[Tl(dota)].H2O shows that the Tl(3+) ion is
      deeply buried in the macrocyclic cavity of the dota(4-) ligand (1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetate) with average Tl-N and Tl-O distances
      of 2.464 and 2.365 A, respectively. The metal ion is directly coordinated to the
      eight donor atoms of the ligand, which results in a twisted square antiprismatic
      (TSAP') coordination around Tl(3+). A multinuclear (1)H, (13)C, and (205)Tl NMR
      study combined with DFT calculations confirmed the TSAP' structure of the complex
      in aqueous solution, which exists as the
      Lambda(lambdalambdalambdalambda)/Delta(deltadeltadeltadelta) enantiomeric pair.
      (205)Tl NMR spectroscopy allowed the protonation constant associated with the
      protonation of the complex according to [Tl(dota)](-) + H(+) ? [Tl(Hdota)] to be
      determined, which turned out to be pK(H)Tl(dota) = 1.4 +/- 0.1. [Tl(dota)](-)
      does not react with Br(-), even when using an excess of the anion, but it forms a
      weak mixed complex with cyanide, [Tl(dota)](-) + CN(-) ? [Tl(dota)(CN)](2-), with
      an equilibrium constant of Kmix = 6.0 +/- 0.8. The dissociation of the
      [Tl(dota)](-) complex was determined by UV-vis spectrophotometry under acidic
      conditions using a large excess of Br(-), and it was found to follow proton
      assisted kinetics and to take place very slowly (~10 days), even in 1 M HClO4,
      with the estimated half-life of the process being in the 10(9) h range at neutral
      pH. The solution dynamics of [Tl(dota)](-) were investigated using (13)C NMR
      spectroscopy and DFT calculations. The (13)C NMR spectra recorded at low
      temperature (272 K) point to C4 symmetry of the complex in solution, which
      averages to C4v as the temperature increases. This dynamic behavior was
      attributed to the Lambda(lambdalambdalambdalambda) <->
      Delta(deltadeltadeltadelta) enantiomerization process, which involves both the
      inversion of the macrocyclic unit and the rotation of the pendant arms. According
      to our calculations, the arm-rotation process limits the
      Lambda(lambdalambdalambdalambda) <-> Delta(deltadeltadeltadelta) interconversion.

PMID- 25977978
TI  - Developmental Effects Determine Submaximal Arterial Oxygen Saturation in Peruvian
      Quechua.
AB  - Kiyamu, Melisa, Fabiola Leon-Velarde, Maria Rivera-Chira, Gianpietro Elias, and
      Tom D. Brutsaert. Developmental effects determine submaximal arterial oxygen
      saturation in Peruvian Quechua. High Alt Med Biol 16, 138-146, 2015.--Andean high
      altitude natives show higher arterial oxygen saturation (Sao(2)) during exercise
      in hypoxia, compared to acclimatized sojourners. In order to evaluate the effects
      of life-long exposure to high altitude on Sao(2), we studied two groups of well
      matched, self-identified Peruvian Quechua natives who differed in their
      developmental exposure to hypoxia before and after a 2-month training period.
      Male and female volunteers (18-35 years) were recruited in Lima, Peru (150 m).
      The two groups were: a) Individuals who were born and raised at sea-level (BSL,
      n=34) and b) Individuals who were born and raised at high altitude (BHA, n=32),
      but who migrated to sea-level as adults (>16 years old). Exercise testing was
      conducted using a submaximal exercise protocol in normobaric hypoxia in Lima
      (BP=750 mmHg, Fio(2)=0.12), in order to measure Sao(2) (%), ventilation (VE
      L/min) and oxygen consumption (Vo(2), L/min). Repeated-measures ANOVA,
      controlling for VE/VO(2) (L/min) and sex during the submaximal protocol showed
      that BHA maintained higher Sao(2) (%) compared to BSL at all workloads before
      (p=0.005) and after training (p=0.017). As expected, both groups showed a
      decrease in Sao(2) (%) (p<0.001), as workload increased. Resting Sao(2) levels
      were not found to be different between groups. The results suggest that
      developmental exposure to altitude contributes to the maintenance of higher
      Sao(2) levels during submaximal exercise at hypoxia.

PMID- 25977979
TI  - What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A
      Quantitative Imaging Study.
AB  - BACKGROUND: A previous PET-CT imaging study of 14 bronchoconstricted asthmatic
      subjects showed that peripheral aerosol deposition was highly variable among
      subjects and lobes. The aim of this work was to identify and quantify factors
      responsible for this variability. METHODS: A theoretical framework was formulated
      to integrate four factors affecting aerosol deposition: differences in
      ventilation, in how air vs. aerosol distribute at each bifurcation, in the
      fraction of aerosol escaping feeding airways, and in the fraction of aerosol
      reaching the periphery that is exhaled. These factors were quantified in 12 of
      the subjects using PET-CT measurements of relative specific deposition sD*,
      relative specific ventilation sV* (measured with dynamic PET or estimated as
      change in expansion between two static HRCTs), average lobar expansion FVOL, and
      breathing frequency measured during aerosol inhalation fN. RESULTS: The fraction
      of the variance of sD* explained by sV* (0.38), by bifurcation effects (0.38),
      and by differences in deposition along feeding airways (0.31) were similar in
      magnitude. We could not directly estimate the contribution of aerosol that was
      exhaled. Differences in expansion did not explain any fraction of the variability
      in sD* among lobes. The dependence of sD* on sV* was high in subjects breathing
      with low fN, but weakened among those breathing faster. Finally, sD*/sV* showed
      positive dependence on FVOL among low fN subjects, while the dependence was
      negative among high fN subjects. CONCLUSION: The theoretical framework allowed us
      to analyze experimentally measured aerosol deposition imaging data. When
      considering bronchoconstricted asthmatic subjects, a dynamic measurement of
      ventilation is required to evaluate its effect on aerosol transport. The
      mechanisms behind the identified effects of fN and FVOL on aerosol deposition
      need further study and may have important implications for aerosol therapy in
      subjects with heterogeneous ventilation.

PMID- 25977980
TI  - How Culture Influences the "Social" in Social Media: Socializing and Advertising
      on Smartphones in India and the United States.
AB  - The importance of the mobile phone is evidenced by predictions that there will be
      1.76 billion smartphone users worldwide at the start of 2015. A country that is
      spearheading this movement toward the digital era is India. To illustrate this,
      India is expected to surpass the United States in 2015 and record the second
      highest smartphone sales globally. Despite the rising penetration and adoption of
      smartphones, there is limited advertising research that sheds light on the Indian
      smartphone user. The current study aims to fill that void by cross-culturally
      comparing a national online panel of smartphone users from India (n=158) with
      users from the United States (n=114). Findings reveal that entertainment impacts
      Indians' attitudes toward smartphone advertising while informativeness is
      stronger for the American sample. Collectivism was found to be the driving force
      behind socializing activities on social networking sites for Indian consumers.
      Implications are discussed. 

PMID- 25977981
TI  - Structure-Guided Design of Highly Selective and Potent Covalent Inhibitors of
      ERK1/2.
AB  - The RAS/RAF/MEK/ERK signaling pathway has been targeted with a number of small
      molecule inhibitors in oncology clinical development across multiple disease
      indications. Importantly, cell lines with acquired resistance to B-RAF and MEK
      inhibitors have been shown to maintain sensitivity to ERK1/2 inhibition by small
      molecule inhibitors. There are a number of selective, noncovalent ERK1/2
      inhibitors reported along with the promiscuous hypothemycin (and related
      analogues) that act via a covalent mechanism of action. This article reports the
      identification of multiple series of highly selective covalent ERK1/2 inhibitors
      informed by structure-based drug design (SBDD). As a starting point for these
      covalent inhibitors, reported ERK1/2 inhibitors and a chemical series identified
      via high-throughput screening were exploited. These approaches resulted in the
      identification of selective covalent tool compounds for potential in vitro and in
      vivo studies to assess the risks and or benefits of targeting this pathway
      through such a mechanism of action. 

PMID- 25977982
TI  - Cilnidipine but not amlodipine suppresses sympathetic activation elicited by
      isometric exercise in hypertensive patients.
AB  - Pupillometry was used to evaluate the effects of the calcium channel blockers
      cilnidipine (CL) and amlodipine (AM) on changes in autonomic nervous activity
      induced by isometric exercise in patients with hypertension. After handgrip
      exercise, the velocity of miosis increased in both the CL and AM groups. However,
      the velocity of mydriasis increased in only the AM group. Velocity slopes of
      miosis and mydriasis were smaller in the CL group than in the AM group. The low
      to-high frequency ratio obtained from pulse wave analysis increased in only the
      AM group. Sympathetic activation elicited by isometric exercise was suppressed
      more effectively by CL than by AM. 

PMID- 25977983
TI  - The critical role of membralin in postnatal motor neuron survival and disease.
AB  - Hitherto, membralin has been a protein of unknown function. Here, we show that
      membralin mutant mice manifest a severe and early-onset motor neuron disease in
      an autosomal recessive manner, dying by postnatal day 5-6. Selective death of
      lower motor neurons, including those innervating the limbs, intercostal muscles,
      and diaphragm, is predominantly responsible for this fatal phenotype. Neural
      expression of a membralin transgene completely rescues membralin mutant mice.
      Mechanistically, we show that membralin interacts with Erlin2, an endoplasmic
      reticulum (ER) membrane protein that is located in lipid rafts and known to be
      important in ER-associated protein degradation (ERAD). Accordingly, the
      degradation rate of ERAD substrates is attenuated in cells lacking membralin.
      Membralin mutations or deficiency in mouse models induces ER stress, rendering
      neurons more vulnerable to cell death. Our study reveals a critical role of
      membralin in motor neuron survival and suggests a novel mechanism for early-onset
      motor neuron disease. 

PMID- 25977984
TI  - Catastrophic chromosomal restructuring during genome elimination in plants.
AB  - Genome instability is associated with mitotic errors and cancer. This phenomenon
      can lead to deleterious rearrangements, but also genetic novelty, and many
      questions regarding its genesis, fate and evolutionary role remain unanswered.
      Here, we describe extreme chromosomal restructuring during genome elimination, a
      process resulting from hybridization of Arabidopsis plants expressing different
      centromere histones H3. Shattered chromosomes are formed from the genome of the
      haploid inducer, consistent with genomic catastrophes affecting a single, laggard
      chromosome compartmentalized within a micronucleus. Analysis of breakpoint
      junctions implicates breaks followed by repair through non-homologous end joining
      (NHEJ) or stalled fork repair. Furthermore, mutation of required NHEJ factor DNA
      Ligase 4 results in enhanced haploid recovery. Lastly, heritability and stability
      of a rearranged chromosome suggest a potential for enduring genomic novelty.
      These findings provide a tractable, natural system towards investigating the
      causes and mechanisms of complex genomic rearrangements similar to those
      associated with several human disorders. 

PMID- 25977985
TI  - Vitamin C Deficiency Causes Severe Defects in the Development of the Neonatal
      Cerebellum and in the Motor Behaviors of Gulo(-/-) Mice.
AB  - AIMS: The developing brain of a neonate is particularly susceptible to damage by
      vitamin C deficiency because of its rapid growth and immature antioxidant system.
      Cognitive impairment and sensory motor deficits are found in the adult brain upon
      vitamin C deficiency. Therefore, the aim of this study was to clarify the role of
      vitamin C in its own right and its related mechanisms in Gulo(-/-) mice incapable
      of synthesizing vitamin C. RESULTS: When vitamin C supplementation was ceased for
      2 weeks until delivery, stillbirths and a significant reduction in neonatal mice
      were observed and the growth of neonates was remarkably decreased. In addition,
      intraparenchymal hemorrhages were found in most of the brains, especially in the
      stillborn neonates. In addition, the levels of malondialdehyde (MDA) and 8
      isoprostanes were increased and structural abnormalities were found in the
      cortex, hippocampus, and cerebellum. Especially, vitamin C deficiency caused the
      failure of or a delay in the formation of cerebellar fissures accompanied by
      abnormal foliation and altered Purkinje cell alignment. In the developed adult
      brains from vitamin C-deficient Gulo(-/-) mice, the levels of glutathione, MDA,
      nitrate, IL-6, TNF-alpha, and Bax were increased and the expression of the GABRA6
      and calbindin-28k was decreased. Due to atrophy of the granule and Purkinje
      cells, the motor behavior of vitamin C-deficient Gulo(-/-) mice declined.
      INNOVATION AND CONCLUSION: Vitamin C deficiency during gestation induces
      intraparenchymal hemorrhages and severe defects in the development of the
      cerebellum. In fully developed brains, it induces the functional impairment by
      altering the cellular composition in the cerebellum.

PMID- 25977986
TI  - Neoadjuvant chemotherapy in controlling lymph node metastasis for locally
      advanced gastric cancer in a Chinese population.
AB  - This study aimed to evaluate the efficacy of FOLFOX6, SOX and XELOX as
      neoadjuvant chemotherapy for advanced gastric cancer. The study retrospectively
      assessed clinicopathological data of patients who received a radical D2
      gastrectomy for gastric cancer from January 2010 to January 2013.The patients
      were either not administered neoadjuvant chemotherapy (control) or were given
      FOLFOX6, SOX and XELOX prior to surgery. The metastatic rate was also higher for
      the control group compared with the three chemotherapy regimens in N2 station
      lymph nodes (P < 0.001). The SOX group had significantly lower metastatic total
      and N2 station lymph nodes than FOLFOX6 and XELOX (P < 0.01). The frequency of
      metastatic lymph nodes relative to total lymph nodes examined was 9.9, 6.6, 3.9
      and 5.3% for control, FOLFOX6, SOX and XELOX groups, respectively. In conclusion,
      SOX may be the most effective of these treatments as preoperative chemotherapy
      for Chinese patients with advanced gastric cancer. 

PMID- 25977987
TI  - Characterization of Recombinant Monoclonal Antibody Charge Variants Using OFFGEL
      Fractionation, Weak Anion Exchange Chromatography, and Mass Spectrometry.
AB  - Recombinant monoclonal antibody charge heterogeneity has been commonly observed
      as multiple bands or peaks when analyzed by charge-based analytical methods such
      as isoelectric focusing electrophoresis and cation or anion exchange
      chromatography. Those charge variants have been separated by some of the above
      mentioned methods and used for detailed characterization. The utility of a
      combination of OFFGEL fractionation and weak anion exchange chromatography to
      separate the charge variants of a recombinant monoclonal antibody was
      demonstrated in the current study. Charge variants were separated into various
      fractions of high purity and then analyzed thoroughly by liquid chromatography
      mass spectrometry. Analysis of intact molecular weights identified the presence
      of heavy chain leader sequence, C-terminal lysine, and C-terminal amidation. The
      identified modifications were further localized into different regions of the
      antibody from analysis of antibody fragments obtained from FabRICATOR digestion.
      Analysis of tryptic peptides from various fractions further confirmed the
      previously identified modifications in the basic variants. Asparagine deamidation
      and aspartate isomerization were identified in acidic fractions from analysis of
      tryptic peptides. Basic variants have been fully accounted for by the identified
      modifications. However, only a portion of the acidic variants can be explained by
      deamidation and isomerization, suggesting that additional modifications are yet
      to be identified or acidic variants are an ensemble of molecules with different
      structures. 

PMID- 25977988
TI  - An active inference and epistemic value view of metacognition.
AB  - Metacognition concerns our monitoring and control of mental operations (knowing
      what you know). Much thinking about metacognition is liable to fall foul of the
      classic homunculus problem: Nobody can specify who or what does the
      "metacognition." We describe how the Active Inference and Epistemic Value (AIEV)
      model offers an operationalization of epistemic behaviors which can explain two
      example metacognitive phenomena: Control and monitoring of word learning, and the
      search for unretrieved information in the feeling of knowing. Curiosity drives a
      search forward, but it is held in check by considering the utility of what is
      retrieved from memory. 

PMID- 25977989
TI  - Dispersing perylene diimide/SWCNT hybrids: structural insights at the molecular
      level and fabricating advanced materials.
AB  - The unique properties of carbon nanotubes (CNT) are advantageous for emerging
      applications. Yet, the CNT insolubility hampers their potential. Approaches based
      on covalent and noncovalent methodologies have been tested to realize stable
      dispersions of CNTs. Noncovalent approaches are of particular interest as they
      preserve the CNT's structures and properties. We report on hybrids, in which
      perylene diimide (PDI) amphiphiles are noncovalently immobilized onto single wall
      carbon nanotubes (SWCNT). The resulting hybrids were dispersed and exfoliated
      both in water and organic solvents in the presence of two different PDI
      derivatives, PP2b and PP3a. The dispersions were investigated using cryogenic
      transmission electron microscopy (cryo-TEM), providing unique structural insights
      into the exfoliation. A helical arrangement of PP2b assemblies on SWCNTs
      dominates in aqueous dispersions, while a single layer of PP2b and PP3a was found
      on SWCNTs in organic dispersions. The dispersions were probed by steady-state and
      time-resolved spectroscopies, revealing appreciable charge redistribution in the
      ground state, and an efficient electron transfer from SWCNTs to PDIs in the
      excited state. We also fabricated hybrid materials from the PP2b/SWCNT
      dispersions. A supramolecular membrane was prepared from aqueous dispersions and
      used for size-selective separation of gold nanoparticles. Hybrid buckypaper films
      were prepared from the organic dispersions. In the latter, high conductivity
      results from enhanced electronic communication and favorable morphology within
      the hybrid material. Our findings shed light onto SWCNT/dispersant molecular
      interactions, and introduce a versatile approach toward universal solution
      processing of SWCNT-based materials. 

PMID- 25977990
TI  - Effect of ion-chelating chain lengths in thiophene-based monomers on in situ
      photoelectrochemical polymerization and photovoltaic performances.
AB  - We synthesized thiophene-based monomers (bis-EDOTs) with different ethylene
      glycol oligomer (EGO) lengths (TBO3, TBO4, and TBO5) and investigated their
      polymerization characteristics during photoelectrochemical polymerization (PEP)
      at the surfaces of dye (D205)-sensitized TiO2 nanocrystalline particles. During
      the PEP reaction, monomers were expected to diffuse toward neighboring dyes
      through the growing polymer layers to enable continuous chain growth. We found
      that the less bulky monomer (TBO3) formed a more compact polymer layer with a
      high molecular weight. Its diffusion to the active sites through the resulting
      growing polymer layer was, therefore, limited. We deployed layers of the polymers
      (PTBO3, PTBO4, and PTBO5) in iodine-free solid-state hybrid solar cells to
      investigate the lithium ion chelating properties of the polymers as a function of
      the number of oxygen atoms present in the EGOs. PTBO4 and PTBO5 were capable of
      chelating lithium ions, yielding a photovoltaic performance that was 142% of the
      performance obtained without the polymer layers (3.0->5.2%).

PMID- 25977991
TI  - Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of
      Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age,
      and Sex.
AB  - Global personalized medicine demands the characterization of person-to-person and
      between-population differences in drug pharmacokinetics and pharmacodynamics.
      CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and
      environmental factors. CYP2C9 genotype-based dose recommendations (e.g., for
      warfarin) is advocated. However, the overall contribution of genotype for
      variation in enzyme activity may differ between populations. We evaluated the
      importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9
      enzyme activity. CYP2C9 genotype and phenotype was determined in 148 Swedes and
      146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assessed using
      urinary losartan/metabolite E-3174 ratio. The frequency of CYP2C9 defective
      variant alleles (*2 and *3) was significantly higher in Swedes (10.8% and 12.5%)
      than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was
      significantly lower in Swedes compared to Koreans (p<0.0001). In a univariate
      analysis, age, weight, ethnicity, genotype, and smoking were significant
      predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated
      ethnicity, genotype, and smoking remained as significant predictors of CYP2C9
      enzyme activity, accounting for 50% of the total variance. In both study
      populations, CYP2C9 genotype was a significant predictor of CYP2C9 enzyme
      activity, but its contribution in explaining the total variance was lower in
      Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower
      CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively
      due to CYP2C9 pharmacogenetic variations. Ethnicity and environment factors need
      to be considered together with genotype for population-specific dose optimization
      and global personalized medicine.

PMID- 25977993
TI  - Variability of Automated Intraoperative ST Segment Values Predicts Postoperative
      Troponin Elevation.
AB  - BACKGROUND: Intraoperative electrocardiographic monitoring is considered a
      standard of care. However, there are no evidence-based algorithms for using
      intraoperative ST segment data to identify patients at high risk for adverse
      perioperative cardiac events. Therefore, we performed an exploratory study of
      statistical measures summarizing intraoperative ST segment values determine
      whether the variability of these measurements was associated with adverse
      postoperative events. We hypothesized that elevation, depression, and variability
      of ST segments captured in an anesthesia information management system are
      associated with postoperative serum troponin elevation. METHODS: We conducted a
      single-institution, retrospective study of intraoperative automated ST segment
      measurements from leads I, II, and III, which were recorded in the electronic
      anesthesia record of adult patients undergoing noncardiac surgery. The maximum,
      minimum, mean, and SD of ST segment values were entered into logistic regression
      models to find independent associations with myocardial injury, defined as an
      elevated serum troponin concentration during the 7 days after surgery.
      Performance of these models was assessed by measuring the area under the receiver
      operator characteristic curve. The net reclassification improvement was
      calculated to quantify the amount of information that the ST segment values
      analysis added regarding the ability to predict postoperative troponin elevation.
      RESULTS: Of 81,011 subjects, 4504 (5.6%) had postoperative myocardial injury.
      After adjusting for patient characteristics, the ST segment maximal depression
      (e.g., lead I: odds ratio [OR], 1.66; 95% confidence interval [CI], 1.26-2.19; P
      = 0.0004), maximal elevation (e.g., lead I: OR, 1.70; 95% CI, 1.34-2.17; P <
      0.0001), and SD (e.g., lead I: OR, 0.16; 95% CI, 0.06-0.42; P = 0.0002) were
      found to have statistically significant associations with myocardial injury.
      Increased SD was associated with decreased risk when accounting for the maximal
      amount of ST segment depression and elevation and for patient characteristics.
      The ST segment summary statistics model had fair discrimination, with an area
      under the receiver operator characteristic curve of 0.71 (95% CI, 0.68-0.73).
      Addition of ST segment data produced a net reclassification improvement of 0.0345
      (95% CI, 0.00016-0.0591; P = 0.0474). CONCLUSIONS: Analysis of automated ST
      segment values obtained during anesthesia may be useful for improving the
      prediction of postoperative troponin elevation.

PMID- 25977992
TI  - A Comparison of Differences Between the Systemic Pharmacokinetics of
      Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A
      Prospective, Randomized, Multicenter, Double-Blind Controlled Trial.
AB  - BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides
      adequate postoperative pain management by minimizing side effects related to IV
      opioids and improving patient outcome. The safety profile of different drugs can
      be better estimated by comparing their pharmacokinetic profiles than by
      considering their objective side effects. Because levobupivacaine and ropivacaine
      have different pharmacokinetic properties, our aim was to investigate whether
      there is a difference in the pharmacokinetic variability of the 2 drugs in a
      homogeneous population undergoing continuous epidural infusion. This double
      blind, multicenter, randomized, controlled trial study was designed to compare
      the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine
      0.125% or ropivacaine 0.2% for postoperative pain management in adult patients
      who had undergone major abdominal, urological, or gynecological surgery. This
      study is focused on the evaluation of the coefficient of variation (CV) to assess
      the equivalence in the systemic exposure and interindividual variability between
      levobupivacaine and ropivacaine and, therefore, the possible differences in the
      predictability of the plasmatic concentrations of the 2 drugs during thoracic
      epidural infusion. METHODS: One hundred eighty-one adults undergoing major
      abdominal surgery were enrolled in the study. Patients were randomized to receive
      an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 MUg/mL or of
      ropivacaine 0.2% + sufentanil 0.75 MUg/mL at 5 mL/h for 48 hours. The primary end
      point of this study was to analyze the variability of plasma concentration of
      levobupivacaine and ropivacaine via an area under the curve within a range of 15%
      of the CV during 48 hours of continuous epidural infusion. The CV shows how the
      concentration values of local anesthetics are scattered around the median
      concentration value, thus indicating the extent to which plasma concentration is
      predictable during infusion. Secondary end points were to assess the
      pharmacologic profile of the local anesthetics used in the study, including an
      analysis of mean peak plasma concentrations, and also to assess plasma clearance,
      side effects, pain intensity (measured with a verbal numeric ranging score, i.e.,
      static Numeric Rating Scale [NRS] and dynamic NRS]), and the need for rescue
      doses. RESULTS: The comparison between the 2 CVs showed no statistical
      difference: the difference between area under the curve was within the range of
      15%. The CV was 0.54 for levobupivacaine and 0.51 for ropivacaine (P = 0.725).
      The plasma concentrations of ropivacaine approached the Cmax significantly faster
      than those of levobupivacaine. Clearance of ropivacaine decreases with increasing
      patient age. There were no significant differences in NRS, dynamic NRS scores,
      the number of rescue doses, or in side effects between groups. CONCLUSIONS:
      Considering the CV, the interindividual variability of plasma concentration for
      levobupivacaine and ropivacaine is equivalent after thoracic epidural infusion in
      adults. We found a reduction in clearance of ropivacaine depending on patient
      age, but this finding could be the result of some limitations of our study. The
      steady-state concentration was not reached during the 48-hour infusion and the
      behavior of plasma concentrations of ropivacaine and levobupivacaine during
      continuous infusions lasting more than 48 hours remains to be investigated,
      because they could reach toxic levels. Finally, no differences in the clinical
      efficacy or in the incidence of adverse effects between groups were found for
      either local anesthetic.

PMID- 25977994
TI  - Transport of carboxyl-functionalized carbon black nanoparticles in saturated
      porous media: Column experiments and model analyses.
AB  - The aim of this study was to investigate the transport behavior of carboxyl
      functionalized carbon black nanoparticles (CBNPs) in porous media including
      quartz sand, iron oxide-coated sand (IOCS), and aluminum oxide-coated sand
      (AOCS). Two sets of column experiments were performed under saturated flow
      conditions for potassium chloride (KCl), a conservative tracer, and CBNPs.
      Breakthrough curves were analyzed to obtain mass recovery and one-dimensional
      transport model parameters. The first set of experiments was conducted to examine
      the effects of metal (Fe, Al) oxides and flow rate (0.25 and 0.5 mL min(-1)) on
      the transport of CBNPs suspended in deionized water. The results showed that the
      mass recovery of CBNPs in quartz sand (flow rate=0.5 mL min(-1)) was 83.1%,
      whereas no breakthrough of CBNPs (mass recovery=0%) was observed in IOCS and AOCS
      at the same flow rate, indicating that metal (Fe, Al) oxides can play a
      significant role in the attachment of CBNPs to porous media. In addition, the
      mass recovery of CBNPs in quartz sand decreased to 76.1% as the flow rate
      decreased to 0.25 mL min(-1). Interaction energy profiles for CBNP-porous media
      were calculated using DLVO theory for sphere-plate geometry, demonstrating that
      the interaction energy for CBNP-quartz sand was repulsive, whereas the
      interaction energies for CBNP-IOCS and CBNP-AOCS were attractive with no energy
      barriers. The second set of experiments was conducted in quartz sand to observe
      the effect of ionic strength (NaCl=0.1 and 1.0mM; CaCl2=0.01 and 0.1mM) and pH
      (pH=4.5 and 5.4) on the transport of CBNPs suspended in electrolyte. The results
      showed that the mass recoveries of CBNPs in NaCl=0.1 and 1.0mM were 65.3 and
      6.4%, respectively. The mass recoveries of CBNPs in CaCl2=0.01 and 0.1mM were
      81.6 and 6.3%, respectively. These results demonstrated that CBNP attachment to
      quartz sand can be enhanced by increasing the electrolyte concentration.
      Interaction energy profiles demonstrated that the interaction energy profile for
      CBNP-quartz sand was compressed and that the energy barrier decreased as the
      electrolyte concentration increased. Furthermore, the mass recovery of CBNPs in
      the presence of divalent ions (CaCl2=0.1 mM) was far lower than that in the
      presence of monovalent ions (NaCl=0.1 mM), demonstrating a much stronger effect
      of Ca(2+) than Na(+) on CBNP transport. Mass recovery of CBNPs at pH 4.5 was
      55.6%, which was lower than that (83.1%) at pH 5.4, indicating that CBNP
      attachment to quartz sand can be enhanced by decreasing the pH. The sticking
      efficiencies (alpha) calculated from the mass recovery by colloid filtration
      theory were in the range from 2.1*10(-2) to 4.5*10(-1), which were far greater
      than the values (2.56*10(-6)-3.33*10(-2)) of theoretical sticking efficiencies
      (alphatheory) calculated from the DLVO energy by the Maxwell model.

PMID- 25977996
TI  - A new trichostatin analog from Streptomyces sp. CPCC 203909.
AB  - A new trichostatin analog (1) and two known analogs (2, 3) have been isolated
      from the rice fermentation of the Streptomyces sp. CPCC 203909. Their structures
      were determined by spectroscopic and chemical methods. The absolute
      configurations of 1 were assigned by Marfey's method, combined with comparing the
      NMR and circular dichroism spectroscopic data of 2 and 3. Compound 1 showed
      cytotoxicity against human embryonic kidney 293 cell line with IC50 value of 39.2
      MUM.

PMID- 25977997
TI  - Generation of stable orthogonal gradients of chemical concentration and substrate
      stiffness in a microfluidic device.
AB  - Cellular responses to chemical cues are at the core of a myriad of fundamental
      biological processes ranging from embryonic development to cancer metastasis.
      Most of these biological processes are also influenced by mechanical cues such as
      the stiffness of the extracellular matrix. How a biological function is
      influenced by a synergy between chemical concentration and extracellular matrix
      stiffness is largely unknown, however, because no current strategy enables the
      integration of both types of cues in a single experiment. Here we present a
      robust microfluidic device that generates a stable, linear and diffusive chemical
      gradient over a biocompatible hydrogel with a well-defined stiffness gradient.
      Device fabrication relies on patterned PSA (Pressure Sensitive Adhesive) stacks
      that can be implemented with minimal cost and lab equipment. This technique is
      suitable for long-term observation of cell migration and application of traction
      force microscopy. We validate our device by testing MDCK cell scattering in
      response to perpendicular gradients of hepatocyte growth factor (HGF) and
      substrate stiffness. 

PMID- 25977995
TI  - Involvement of Immune Responses in the Efficacy of Cord Blood Cell Therapy for
      Cerebral Palsy.
AB  - This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients
      with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial
      and also assessed factors and mechanisms related to the efficacy. Thirty-six
      children (ages 6 months to 20 years old) with CP were enrolled and treated with
      UCB or a placebo. Muscle strength and gross motor function were evaluated at
      baseline and 1, 3, and 6 months after treatment. Along with function
      measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission
      tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels
      were quantitated in serial blood samples. The UCB group showed greater
      improvements in muscle strength than the controls at 1 (0.94 vs. -0.35,
      respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB
      group also showed greater improvements in gross motor performance than the
      control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally,
      positron emission tomography scans revealed decreased periventricular
      inflammation in patients administered UCB, compared with those treated with a
      placebo. Correlating with enhanced gross motor function, elevations in plasma
      pentraxin 3 and interleukin-8 levels were observed for up to 12 days after
      treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll
      like receptor 4 were noted at 1 day after treatment in the UCB group, and they
      were correlated with increased muscle strength at 3 months post-treatment. In
      this trial, treatment with UCB alone improved motor outcomes and induced systemic
      immune reactions and anti-inflammatory changes in the brain. Generally, motor
      outcomes were positively correlated with the number of UCB cells administered: a
      higher number of cells resulted in better outcomes. Nevertheless, future trials
      are needed to confirm the long-term efficacy of UCB therapy, as the follow-up
      duration of the present trial was short. 

PMID- 25977999
TI  - Gallium and indium complexes containing the bis(imino)phenoxide ligand:
      synthesis, structural characterization and polymerization studies.
AB  - A series of gallium and indium complexes containing a bis(imino)phenolate ligand
      framework were synthesized and completely characterized with different
      spectroscopic techniques. The molecular structures of a few complexes were
      determined using single crystal X-ray diffraction studies. These compounds were
      found to be extremely active towards the bulk ring opening polymerization (ROP)
      of lactides yielding polymers with high number average molecular weight (Mn) and
      controlled molecular weight distributions (MWDs). The neutral complexes produce
      isotactic enriched poly(lactic acid) (PLA) from rac-lactide (rac-LA) under melt
      conditions, whereas the ionic complex produces atactic PLA. The polymerizations
      are controlled, as evidenced by the narrow molecular distribution (MWDs) of the
      isolated polymers in addition to the linear nature of number average molecular
      weight (Mn) versus conversion plots with variations in monomer to catalyst
      ratios. The kinetic and mechanistic studies associated with these polymerizations
      have been performed. 

PMID- 25977998
TI  - Different ATM Signaling in Response to Chromium(VI) Metabolism via Ascorbate and
      Nonascorbate Reduction: Implications for in Vitro Models and Toxicogenomics.
AB  - BACKGROUND: Carcinogenic hexavalent chromium [Cr(VI)] requires cellular reduction
      to generate DNA damage. Metabolism of Cr(VI) by its principal reducer ascorbate
      (Asc) lacks a Cr(V) intermediate, which is abundant in reactions with a minor
      reducing agent, glutathione. Cultured cells are widely used in mechanistic
      studies of Cr(VI) toxicity; however, they typically contain < 1% of normal Asc
      levels. Asc deficiency is also expected to diminish protection against reactive
      oxygen species. OBJECTIVES: We assessed how the presence of Asc in cells affects
      their stress signaling and survival responses to chromate. METHODS: We
      investigated the effects of Asc restoration in human lung H460 cells and normal
      human lung fibroblasts on the activation and functional role of ATM kinase, which
      controls DNA damage responses involving several hundreds of proteins. RESULTS:
      Treatment of standard cultures with Cr(VI) strongly activated ATM, as indicated
      by its automodification at Ser1981 and by phosphorylation of checkpoint kinase 2
      (CHK2) and chromatin/transcription regulator KRAB-associated protein 1 (KAP1).
      Confirming the importance of activated ATM, its inhibition impaired replication
      recovery and clonogenic survival. In contrast, fully Asc-restored cells lacked
      ATM activation by Cr(VI), and ATM silencing produced no significant effects on
      p53 stabilization, apoptosis, replication recovery, or clonogenic survival. Dose
      dependence studies found a close correlation between ATM activation and the
      extent of Cr(VI) reduction by glutathione. CONCLUSIONS: Asc restoration in
      cultured cells dramatically altered their stress responses to Cr(VI) by
      preventing activation of the oxidant-sensitive ATM network. We suggest that
      toxicogenomic and other cell response-based approaches likely underestimate
      Cr(VI) genotoxicity when standard ATM-activating carcinogens are used as
      references. CITATION: Luczak MW, Green SE, Zhitkovich A. 2016. Different ATM
      signaling in response to chromium(VI) metabolism via ascorbate and nonascorbate
      reduction: implications for in vitro models and toxicogenomics. Environ Health
      Perspect 124:61-66; http://dx.doi.org/10.1289/ehp.1409434.

PMID- 25978001
TI  - Overview of the effect of salts on biphasic ionic liquid/water solvent extraction
      systems: anion exchange, mutual solubility, and thermomorphic properties.
AB  - Hydrophobic (water-immiscible) ionic liquids (ILs) are frequently used as organic
      phase in solvent extraction studies. These biphasic IL/water extraction systems
      often also contain metal salts or mineral acids, which can significantly affect
      the IL trough (un)wanted anion exchange and changes in the solubility of IL in
      the aqueous phase. In the case of thermomorphic systems, variations in the cloud
      point temperature are also observed. All these effects have important
      repercussions on the choice of IL, suitable for a certain extraction system. In
      this paper, a complete overview of the implications of metal salts on biphasic
      IL/water systems is given. Using the Hofmeister series as a starting point, a
      range of intuitive prediction models are introduced, supported by experimental
      evidence for several hydrophobic ILs, relevant to solvent extraction. Particular
      emphasis is placed on the IL betainium bis(trifluoromethylsulfonyl)imide
      [Hbet][Tf2N]. The aim of this work is to provide a comprehensive interpretation
      of the observed effects of metal salts, so that it can be used to predict the
      effect on any given biphasic IL/water system instead of relying on case-by-case
      reports. These prediction tools for the impact of metal salts can be useful to
      optimize IL synthesis procedures, extraction systems and thermomorphic
      properties. Some new insights are also provided for the rational design of ILs
      with UCST or LCST behavior based on the choice of IL anion. 

PMID- 25978000
TI  - Mad2 Inhibitor-1 (M2I-1): A Small Molecule Protein-Protein Interaction Inhibitor
      Targeting the Mitotic Spindle Assembly Checkpoint.
AB  - The genetic integrity of each organism depends on the faithful segregation of its
      genome during mitosis. To meet this challenge, a cellular surveillance mechanism,
      termed the spindle assembly checkpoint (SAC), evolved that monitors the correct
      attachment of chromosomes and blocks progression through mitosis if corrections
      are needed. While the central role of the SAC for genome integrity is well
      established, its functional dissection has been hampered by the limited
      availability of appropriate small molecule inhibitors. Using a fluorescence
      polarization-based screen, we identify Mad2 inhibitor-1 (M2I-1), the first small
      molecule inhibitor targeting the binding of Mad2 to Cdc20, an essential protein
      protein interaction (PPI) within the SAC. Based on computational and biochemical
      analyses, we propose that M2I-1 disturbs conformational dynamics of Mad2 critical
      for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens
      the SAC response, indicating that the compound might be active in cells. Thus,
      our study identifies the SAC specific complex formation between Mad2 and Cdc20 as
      a protein-protein interaction that can be targeted by small molecules.

PMID- 25978002
TI  - Hospital ownership, decisions on supervisory board characteristics, and financial
      performance.
AB  - BACKGROUND: Dynamic and complex transformations in the hospital market increase
      the relevance of good corporate governance. However, hospital performance and the
      characteristics of supervisory boards differ depending on ownership. The question
      therefore arises whether hospital owners can influence performance by addressing
      supervisory board characteristics. PURPOSE: The objective of this study is to
      explain differences in the financial performance of hospitals with regard to
      ownership by studying the size and composition of supervisory boards.
      METHODOLOGY: The AMADEUS database was used to collect information on hospital
      financial performance in 2009 and 2010. Business and quality reports, hospital
      websites, and data from health insurer were used to obtain information on
      hospital and board characteristics. The resulting sample consisted of 175 German
      hospital corporations. We utilized ANOVA and regression analysis to test a
      mediation hypothesis that investigated whether decisions regarding board size and
      composition were associated with financial performance and could explain
      performance differences. FINDINGS: Financial performance and board size and
      composition depend on ownership. An increase in board size and greater politician
      participation were negatively associated with all five tested measures of
      financial performance. Furthermore, an increase in physician participation was
      positively associated with one dimension of financial performance, whereas one
      negative relationship was identified for nurse and economist participation. For
      clerics, no associations were found. PRACTICE IMPLICATIONS: Decisions concerning
      board size and composition are important as they relate to hospital financial
      performance. We contribute to existing research by showing that, in addition to
      board size and physician participation, the participation of other professionals
      can also influence financial performance.

PMID- 25978003
TI  - Contributions of relational coordination to care management in accountable care
      organizations: Views of managerial and clinical leaders.
AB  - BACKGROUND: The accountable care organization (ACO) is a new type of health care
      organization incentivized to improve quality of care, improve population health,
      and reduce the cost of care. An ACO's success in meeting these objectives depends
      greatly upon its ability to improve patient care management. Numerous studies
      have found relational coordination to be positively associated with key measures
      of organizational performance in health care organizations, including quality and
      efficiency. PURPOSE: The purpose of this paper is twofold: (a) identify the
      extent to which ACO leaders are aware of the dimensions of relational
      coordination, and (b) identify the ways these leaders believe the dimensions
      influenced care management practices in their organization. METHODOLOGY/APPROACH:
      We performed content analysis of interviews with managerial and clinical leaders
      from a diverse group of 11 ACOs to assess awareness of relational coordination
      and identify the ways that dimensions of relational coordination were perceived
      to influence development of care management practices. FINDINGS: ACO leaders
      mentioned four relational coordination dimensions: shared goals, frequency of
      communication, timeliness of communication, and problem solving communication.
      Three dimensions - shared knowledge of team members' tasks, mutual respect, and
      accuracy of communication - were not mentioned. Our analysis identified numerous
      ways leaders believed the four mentioned dimensions contributed to the
      development of care management, including contributions to standardization of
      care, patient engagement, coordination of care, and care planning. DISCUSSION: We
      propose two hypotheses for future research on relational coordination and care
      management. PRACTICE IMPLICATIONS: If relational coordination is to have a
      beneficial influence on ACO performance, organizational leaders must become more
      aware of relational coordination and its various dimensions and become cognizant
      of relational coordination's influence on care management in their ACO. We
      suggest a number of means by which ACO leaders could become more aware of
      relational coordination and its potential effects.

PMID- 25978004
TI  - The gendered realities and talent management imperatives of women physicians.
AB  - INTRODUCTION: U.S. medicine is increasingly a gender-balanced profession with
      half of all medical school graduates now female. Despite this reality and the
      potentially transformative nature of a large female physician cohort in U.S.
      health care, there is less examination of their workplace realities and the key
      talent management strategies for health care organizations employing women
      physicians. PURPOSE: First, we identify current knowledge about U.S. women
      physician satisfaction, role challenges, and work tradeoffs. Gender theory is
      used to help interpret these workplace realities. Second, we use this information
      to identify talent management strategies health care organizations might consider
      to mitigate the realities and provide greater support for women physicians.
      METHODS: To facilitate our analysis, we conducted a narrative review of published
      research that includes analysis focused on U.S. women physicians for the time
      period 2006-2014. Applying ideas from gender theory, we extrapolated key findings
      from that research related to three issues: satisfaction, role challenges, and
      tradeoffs. Then we synthesized the findings to identify general talent management
      strategies that could address these dynamics proactively while enhancing
      recruitment and retention with respect to women physicians. FINDINGS: U.S. women
      physicians express strong levels of satisfaction, particularly with their
      careers, at the same time they continue to experience gender-based inequities,
      role challenges, and lack of work-life balance in their chosen specialty fields.
      Lack of suitable role models and appropriate mentoring for women physicians, in
      addition to barriers to career advancement, are also prevalent across different
      medical specialties. CONCLUSION: Similar to other occupations and industries,
      gender-based inequities and role strains are very real issues for women
      physicians. Health care organizations must acknowledge these issues and employ
      effective talent management strategies aimed at women doctors if they are to be
      viewed as an employer of choice by this increasingly important occupational
      cohort.

PMID- 25978006
TI  - High-Field Electron Paramagnetic Resonance and Density Functional Theory Study of
      Stable Organic Radicals in Lignin: Influence of the Extraction Process, Botanical
      Origin, and Protonation Reactions on the Radical g Tensor.
AB  - The radical concentrations and g factors of stable organic radicals in different
      lignin preparations were determined by X-band EPR at 9 GHz. We observed that the
      g factors of these radicals are largely determined by the extraction process and
      not by the botanical origin of the lignin. The parameter mostly influencing the g
      factor is the pH value during lignin extraction. This effect was studied in depth
      using high-field EPR spectroscopy at 263 GHz. We were able to determine the gxx,
      gyy, and gzz components of the g tensor of the stable organic radicals in lignin.
      With the enhanced resolution of high-field EPR, distinct radical species could be
      found in this complex polymer. The radical species are assigned to substituted o
      semiquinone radicals and can exist in different protonation states SH3+, SH2, SH1
      , and S2-. The proposed model structures are supported by DFT calculations. The g
      principal values of the proposed structure were all in reasonable agreement with
      the experiments. 

PMID- 25978005
TI  - A phenotypic in vitro model for the main determinants of human whole heart
      function.
AB  - This article details the construction and testing of a phenotypic assay system
      that models in vivo cardiac function in a parallel in vitro environment with
      human stem cell derived cardiomyocytes. The major determinants of human whole
      heart function were experimentally modeled by integrating separate 2D cellular
      systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model
      features a serum-free defined medium to enable both acute and chronic evaluation
      of drugs and toxins. The integration of data from both systems produced
      biologically relevant predictions of cardiac function in response to varying
      concentrations of selected drugs. Sotalol, norepinephrine and verapamil were
      shown to affect the measured parameters according to their specific mechanism of
      action, in agreement with clinical data. This system is applicable for cardiac
      side effect assessment, general toxicology, efficacy studies, and evaluation of
      in vitro cellular disease models in body-on-a-chip systems. 

PMID- 25978007
TI  - Natural products as sources of new fungicides (II): antiphytopathogenic activity
      of 2,4-dihydroxyphenyl ethanone derivatives.
AB  - A series of 17 simple 1-(2,4-dihydroxyphenyl) ethanones were synthesised, and
      their structures characterised by (1)H, (13)C NMR and ESI-MS. Their in vitro
      antifungal activities were evaluated against five phytopathogenic fungi including
      Glomerella cingulate, Botrytis cirerea, Fusarium graminearum, Curvularia lunata
      and Fusarium oxysporum f. sp. vasinfectum by the mycelial growth inhibition
      assay. Compounds 2g and 2h exhibited broad-spectrum inhibitory activity against
      the mycelial growth of the tested pathogens with IC50 values in the range of 16
      36 MUg/mL, and in particular being more active to G. cingulate, with IC50 values
      of 16.50 and 19.25 MUg/mL, respectively, than the other pathogens. Preliminary
      SAR indicated that an alpha,beta-unsaturated ketone unit of the alkyl chain of
      the compounds is the structure requirement for fungicidal action. The results
      suggested that 2g and 2h may be promising leads in the development of new
      antifungal agents. 

PMID- 25978008
TI  - Progress in understanding the genomic basis for adverse drug reactions: a
      comprehensive review and focus on the role of ethnicity.
AB  - A major goal of the field of pharmacogenomics is to identify the genomic causes
      of serious adverse drug reactions (ADRs). Increasingly, genome-wide association
      studies (GWAS) have been used to achieve this goal. In this article, we review
      recent progress in the identification of genetic variants associated with ADRs
      using GWAS and discuss emerging themes from these studies. We also compare
      aspects of GWAS for ADRs to GWAS for common diseases. In the second part of the
      article, we review progress in performing pharmacogenomic research in multi
      ethnic populations and discuss the challenges and opportunities of investigating
      genetic causes of ADRs in ethnically diverse patient populations. 

PMID- 25978009
TI  - A meta-analysis: Do prophylactic antiepileptic drugs in patients with brain
      tumors decrease the incidence of seizures?
AB  - BACKGROUND: Seizures are a potentially devastating complication of brain tumors.
      Several studies in the past have attempted to demonstrate that prophylactic
      antiepileptic drugs (AEDs) in patients with brain tumors can decrease the
      incidence of seizures. However, it is currently unclear whether AEDs should be
      routinely administered to patients with brain tumors who have never had a
      seizure. OBJECTIVE: A meta-analysis of randomized trials was conducted to
      estimate the effectiveness of seizure prophylaxis in people with brain tumors.
      METHODS: A range of electronic databases were searched (1966-2014): MEDLINE, the
      Cochrane Library Database, EMBASE, CINAHL, Web of Science and the Chinese
      Biomedical Database (CBM) without language restrictions. Two independent
      reviewers assessed trials for eligibility and quality, and meta-analysis was
      performed using the STATA 12.0 software. Integrated Odd Ratio (OR) with its
      corresponding 95% confidence interval (95%CI) was calculated. RESULTS: Six RCTs
      were included with a total of 547 patients with brain tumors. The meta-analysis
      results revealed that patients with brain tumors who received prophylactic
      antiepileptic interventions did not have significantly lower epilepsy incidence
      than those in controlled groups (OR=0.939, 95%CI=0.609-1.448, z=0.29, P=0.775).
      Sensitivity analysis suggested the statistical results were robust. No
      publication bias was detected in this meta-analysis (P>0.05). CONCLUSION:
      Although some past studies indicated AEDs can be used in patients with brain
      tumors to relieve epilepsy, present integrated evidences cannot show in
      unequivocal terms that brain tumor patients can benefit from seizure prophylaxis.

PMID- 25978010
TI  - Ultrastructural changes to rat hippocampus in pentylenetetrazol- and kainic acid
      induced status epilepticus: A study using electron microscopy.
AB  - A pentylenetetrazol (PTZ)-induced status epilepticus model in rats was used in
      the study. The brains were studied one month after treatment. Ultrastructural
      observations using electron microscopy performed on the neurons, glial cells, and
      synapses, in the hippocampal CA1 region of epileptic brains, demonstrated the
      following major changes over normal control brain tissue. (i) There is
      ultrastructural alterations in some neurons, glial cells and synapses in the
      hippocampal CA1 region. (ii) The destruction of cellular organelles and
      peripheral, partial or even total chromatolysis in some pyramidal cells and in
      interneurons are observed. Several astrocytes are proliferated or activated.
      Presynaptic terminals with granular vesicles and degenerated presynaptic profiles
      are rarely observed. (iii) The alterations observed are found to be dependent on
      the frequency of seizure activities following the PTZ treatment. It was observed
      that if seizure episodes are frequent and severe, the ultrastructure of
      hippocampal area is significantly changed. Interestingly, the ultrastructure of
      CA1 area is found to be only moderately altered if seizure episodes following the
      status epilepticus are rare and more superficial; (iv) alterations in
      mitochondria and dendrites are among the most common ultrastructural changes
      seen, suggesting cell stress and changes to cellular metabolism. These
      morphological changes, observed in brain neurons in status epilepticus, are a
      reflection of epileptic pathophysiology. Further studies at the chemical and
      molecular level of neurotransmitter release, such as at the level of porosomes
      (secretory portals) at the presynaptic membrane, will further reveal molecular
      details of these changes. 

PMID- 25978011
TI  - A comparative study of smart spectrophotometric methods for simultaneous
      determination of sitagliptin phosphate and metformin hydrochloride in their
      binary mixture.
AB  - Simple, specific, accurate and precise spectrophotometric methods were developed
      and validated for the simultaneous determination of the oral antidiabetic drugs;
      sitagliptin phosphate (STG) and metformin hydrochloride (MET) in combined
      pharmaceutical formulations. Three methods were manipulating ratio spectra
      namely; ratio difference (RD), ratio subtraction (RS) and a novel approach of
      induced amplitude modulation (IAM) methods. The first two methods were used for
      determination of STG, while MET was directly determined by measuring its
      absorbance at lambdamax 232 nm. However, (IAM) was used for the simultaneous
      determination of both drugs. Moreover, another three methods were developed based
      on derivative spectroscopy followed by mathematical manipulation steps namely;
      amplitude factor (P-factor), amplitude subtraction (AS) and modified amplitude
      subtraction (MAS). In addition, in this work the novel sample enrichment
      technique named spectrum addition was adopted. The proposed spectrophotometric
      methods did not require any preliminary separation step. The accuracy, precision
      and linearity ranges of the proposed methods were determined. The selectivity of
      the developed methods was investigated by analyzing laboratory prepared mixtures
      of the drugs and their combined pharmaceutical formulations. Standard deviation
      values were less than 1.5 in the assay of raw materials and tablets. The obtained
      results were statistically compared to that of a reported spectrophotometric
      method. The statistical comparison showed that there was no significant
      difference between the proposed methods and the reported one regarding both
      accuracy and precision.

PMID- 25978014
TI  - Spectroscopic investigation on the production of clay bricks with SCBA waste.
AB  - In this paper, the effect of sugarcane bagasse ash (SCBA) addition to the brick
      making clay has been analyzed using spectroscopic techniques. For that, mixtures
      of brick making clay (BMC) with sugarcane bagasse ash (SCBA) in proportions of 0
      20 wt.% were hydraulic uniaxially pressed and sintered at temperatures of 800
      1100  degrees C. The partial replacement of the brick making clay with SCBA was
      studied with chemical and mineralogical analyzes (XRF and X-ray diffraction). The
      quantitative estimation of minerals was made by FTIR analysis. The results of FT
      IR reveal that kaolinite, quartz, and lignin are predominant, whereas, cellulose
      and calcite are in moderate levels. In addition, magnetite and hematite are found
      in trace level. The overall results reveal that the brick making clay substituted
      with 15 wt.% of SCBA can open up a new path for the fabrication of quality bricks
      at low cost.

PMID- 25978013
TI  - Facilitation of the PED analysis of large molecules by using global coordinates.
AB  - Global coordinates have been found to be useful in the potential energy
      distribution (PED) analyses of the following large molecules: [13]-acene and [33]
      helicene. The global coordinate is defined based on much distanced fragments of
      the analysed molecule, whereas so far, the coordinates used in the analysis were
      based on stretchings, bendings, or torsions of the adjacent atoms. It has been
      shown that the PED analyses performed using the global coordinate and the
      classical ones can lead to exactly the same PED contributions. The global
      coordinates may significantly improve the facility of the analysis of the
      vibrational spectra of large molecules. 

PMID- 25978012
TI  - Leucas aspera mediated multifunctional CeO2 nanoparticles: Structural,
      photoluminescent, photocatalytic and antibacterial properties.
AB  - Spherical shaped cerium dioxide (CeO2) nanoparticles (NPs) were synthesized via
      bio mediated route using Leucas aspera (LA) leaf extract. The NPs were
      characterized by PXRD, SEM, UV-Visible techniques. Photoluminescence (PL),
      photocatalysis and antibacterial properties of NPs were studied. PXRD patterns
      and Rietveld analysis confirm cubic fluorite structure with space group Fm-3m.
      SEM results evident that morphology of the NPs was greatly influenced by the
      concentration of LA leaf extract in the reaction mixture. The band gap energy of
      the NPs was found to be in the range of 2.98-3.4 eV. The photocatalytic activity
      of NPs was evaluated by decolorization of Rhodamine-B (RhB) under UVA and Sun
      light irradiation. CeO2 NPs show intense blue emission with CIE coordinates
      (0.14, 0.22) and average color coordinated temperature value ~148,953 K.
      Therefore the present NPs quite useful for cool LEDs. The superior photocatalytic
      activity was observed for CeO2 NPs with 20 ml LA under both UVA and Sunlight
      irradiation. The enhanced photocatalytic activity and photoluminescent properties
      were attributed to defect induced band gap engineered CeO2 NPs. Further, CeO2
      with 20 ml LA exhibit significant antibacterial activity against Escherichia coli
      (EC) and Staphylococcus aureus (SA). These findings show great promise of CeO2
      NPs as multifunctional material for various applications.

PMID- 25978015
TI  - Polypyrrole-coated magnetic nanoparticles as an efficient adsorbent for RB19
      synthetic textile dye: Removal and kinetic study.
AB  - The present work deals with the first attempt to study the removal of synthetic
      textile dye, reactive blue 19 (RB19), using the magnetic Fe3O4 nanoparticles
      modified by pyrrole (PPy@Fe3O4 MNPs) as an efficient adsorbent. The nanoadsorbent
      was synthesized using chemical co-precipitation. Scanning electron microscopy and
      FT-IR were used to characterize nanoparticles. Factors affecting the dye
      adsorption including the pH of the dye solution, amount of adsorbent and contact
      time were also further investigated. Sorption of the RB19 on PPy@Fe3O4 MNPs
      reached to equilibrium at contact time less than 10 min and fitted well to the
      Langmuir adsorption model with a maximum adsorption capacity of 112.36 mg g(-1).
      Experiments for adsorption kinetic were carried out and the data fitted well
      according to a pseudo-second-order kinetic model. Moreover, the MNPs were
      recovered with over than 90% efficiency using methanol as elution agent.

PMID- 25978016
TI  - A core-shell structured inorganic-organic hybrid nanocomposite for Hg(II) sensing
      and removal.
AB  - In the present paper, a core-shell structured inorganic-organic hybrid
      nanocomposite for Hg(II) sensing and removal was designed and fabricated, where
      the core was composed of superparamagnetic Fe3O4 and the shell consisted of
      molecular silica sieve MCM-41. A rhodamine derived probe was grafted onto the
      backbone of MCM-41 through a silane coupling reagent to control its loading
      content. This probe functionalized core-shell structure was confirmed and
      characterized by XRD analysis, electron microscopy images, IR spectra,
      thermogravimetry and N2 adsorption/desorption isotherms. It was found that the
      emission of this composite increased with increasing Hg(II) concentrations but
      was immune to other metal ions, showing good selectivity and high sensitivity
      towards Hg(II) ions. A linear Stern-Volmer curve was observed with short response
      time. In addition, this composite possessed good Hg(II)-removing and recycling
      performance. 

PMID- 25978017
TI  - Study of cellulolytic enzyme immobilization on copolymers of N-vinylformamide.
AB  - This study was focused on finding of effective carriers suitable for the
      immobilization of cellulase. Copolymers of N-vinylformamide (NFV) and
      divinylbenzene (DVB) were synthesized by free radical crosslinking polymerization
      in inverse suspension. Methyl silicone oil was used as the continuous phase.
      Three polymeric carriers based on P(NVF-co-DVB) with varying degrees of
      crosslinking and spherical particles with different grain sizes were obtained.
      The formamide groups in these carriers were hydrolyzed to amino groups, yielding
      three P(VAm-co-DVB) polymers with vinylamine units. Enzyme, cellulase (Novozym(r)
      476), was immobilized onto carriers with vinylamine (through glutaraldehyde) and
      vinylformamide groups (without glutaraldehyde). The efficiency of the enzyme
      immobilization was determined based on the enzymatic activity of the enzyme
      during the catalytic reaction relative to that of the native enzyme. All tested
      carriers were found to be effective carriers for the immobilization of cellulase.
      However, the catalytic activity of cellulase immobilized on the P(VAM-co
      DVB0.27)/2000/350 carrier was higher than that for the native enzyme. In
      addition, two molecular spectroscopy methods, Fourier-transform absorption
      infrared spectroscopy (FT-IR) and Fourier-transform Raman spectroscopy (FT
      Raman), were used to analyze the carriers. These studies provided complete
      information regarding the structure of the studied copolymers. 

PMID- 25978018
TI  - Structure and vibrations of glutathione studied by vibrational spectroscopy and
      density functional theory.
AB  - The vibrational properties of glutathione have been investigated by infrared
      absorption and Raman spectroscopic techniques, and density functional theory
      calculations at the B3LYP/6-31+G(d,p) level. Assignments of all the
      experimentally observed vibrational bands have been done with the help of
      simulated vibrational spectra and potential energy distribution calculations of
      glutathione water cluster, which includes the effect of hydrogen bonding.
      Optimized molecular parameters of energy minimized structure have been compared
      with the available experimental values. Calculated molecular parameters of
      glutathione-water cluster match well with the experimental values. Some of the
      calculated molecular parameters and vibrational frequencies of vapor phase
      glutathione-water cluster suggest participation of some atoms of glutathione in
      hydrogen bonding. Experimentally observed UV-Visible absorption spectrum of
      glutathione has also been reported. Observed band at 203 nm has been assigned to
      electronic transitions calculated with time dependent density functional theory.

PMID- 25978019
TI  - Rapid discrimination of three marine fish surimi by Tri-step infrared
      spectroscopy combined with Principle Component Regression.
AB  - A Tri-step infrared spectroscopy (Fourier transform infrared spectroscopy (FT-IR)
      integrated with second derivative infrared (SD-IR) spectroscopy and two
      dimensional correlation infrared spectroscopy (2DCOS-IR)) combined with Principal
      Component Regression (PCR) were employed to characterize and discriminate three
      marine fish surimi (white croaker surimi (WCS), hairtail surimi (HS) and red coat
      surimi (RCS)). The three surimi had similar IR macro-fingerprints
      (similarity>0.7) especially for the absorption bands of amide groups. Compared to
      the other two surimi, however, RCS had a middle strong characteristic peak of
      lipids at 1745 cm(-1), indicating that RCS had the highest content of lipids. SD
      IR spectra of the three surimi enhanced the spectral resolution and amplified the
      small differences, especially at about 1682 cm(-1), 1679 cm(-1), 1656 cm(-1) and
      1631 cm(-1), suggesting that the three had different profiles of proteins.
      Moreover, evident differences were observed in 2DCOS-IR spectra of 1500-1800 cm(
      1). WCS had one strong (1620 cm(-1)) and three weak auto-peaks (1520 cm(-1), 1552
      cm(-1), 1706 cm(-1)). HS had three strong (1621 cm(-1), 1648 cm(-1), 1708 cm(-1))
      and two weak auto-peaks (1523 cm(-1), 1553 cm(-1)), whereas RCS had one strong
      (1623 cm(-1)) and three weak auto-peaks (1525 cm(-1), 1709 cm(-1), 1738 cm(-1)).
      Furthermore, sixty batches of surimi (twenty for each surimi) were objectively
      classified by PCR. It was demonstrated that the Tri-step infrared spectroscopy
      combined with PCR could be applicable for discrimination of precious marine fish
      surimi in a direct, rapid and holistic manner.

PMID- 25978020
TI  - Fluorescence quenching studies on the interaction of catechin-quinone with CdTe
      quantum dots. Mechanism elucidation and feasibility studies.
AB  - Changes of the photoluminescent properties of QD in the presence of oxidized
      catechin (CQ) were investigated by absorption, steady-state fluorescence,
      fluorescence lifetime and dynamic light scattering measurements.
      Photoluminescence intensity and fluorescence lifetime was decreasing with
      increasing CQ concentration. Dynamic light scattering technique found the
      hydrodynamic diameter of QD suspension in water is in range of 45 nm, whereas in
      presence of CQ increased to mean values of 67 nm. Calculated from absorption peak
      position of excition band indicated on average QD size of 3.2 nm. Emission
      spectroscopy and time-resolved emission studies confirmed preservation of
      electronic band structure in QD-CQ aggregates. On basis of the presented results,
      the elucidated mechanism of QD fluorescence quenching is a result of the
      interaction between QD and CQ due to electron transfer and electrostatic
      attraction. The results of fluorescence quenching of water-soluble CdTe quantum
      dot (QD) capped with thiocarboxylic acid were used to implement a simple and fast
      method to determine the presence of native antioxidant quinones in aqueous
      solutions. Feasibility studies on this method carried out with oxidized catechin
      showed a linear relation between the QD emission and quencher concentration, in
      range from 1 up to 200 MUM. The wide linear range of concentration dependence
      makes it possible to apply this method for the fast and sensitive detection of
      quinones in solutions.

PMID- 25978021
TI  - A fluoride-sensing receptor based on 2,2'-bis(indolyl)methane by dual-function of
      colorimetry and fluorescence.
AB  - A compound based on 2,2'-bis(indolyl)methane containing nitro group was studied
      as a new anion receptor. It could recognize selectively F(-) by an increasing
      fluorescence signal and a visible color change from colorless to blue. The
      introduction of nitro group induced the spectral dual-function related to the
      deprotonation of N-H protons. 

PMID- 25978022
TI  - Evaluation of the interaction between naringenin and human serum albumin:
      Insights from fluorescence spectroscopy, electrochemical measurement and
      molecular docking.
AB  - Naringenin (Nar) is a flavanone compound found in grapefruits that is endowed
      with diverse pharmacological and biological activities. Here, the interaction
      between Nar and human serum albumin (HSA) was investigated via various methods,
      including fluorescence spectroscopy, electrochemical methods and molecular
      docking. The Stern-Volmer quenching constants inversely correlated with
      temperature, demonstrating that the fluorescence quenching about HSA-Nar system
      is initiated by the formation of a compound, which has confirmed by
      electrochemical measurements. Three-dimensional fluorescence demonstrated that
      Nar induces the slight unfolding of the polypeptides of HSA. The calculated
      thermodynamic parameters suggesting that the binding of Nar to HSA is
      spontaneous, and the mainly force is electrostatic interactions. In addition,
      site marker competitive experiments indicated that Nar binds to HSA both on site
      I (subdomain IIA) and site II (subdomain IIIA), with higher affinity to the
      latter one, consistence with molecular docking. Furthermore, the fluorescence
      resonance energy transfer (FRET) experiment showed the binding distance (r) is
      2.65 nm. And the effects of metal ions on the HSA-Nar system are also discussed.

PMID- 25978023
TI  - Spectrometer calibration protocol for Raman spectra recorded with different
      excitation wavelengths.
AB  - The combination of Raman spectroscopy with chemometrics has gained significant
      importance within the last years to address a broad variety of biomedical and
      life science questions. However, the routine application of chemometric models to
      analyze Raman spectra recorded with Raman devices different from the device used
      to establish the model is extremely challenging due to Raman device specific
      influences on the recorded Raman spectra. Here we report on the influence of
      different non-resonant excitation wavelengths on Raman spectra and propose a
      calibration routine, which corrects for the main part of the spectral differences
      between Raman spectra recorded with different (non-resonant) excitation
      wavelengths. The calibration routine introduced within this contribution is an
      improvement to the known 'standard' calibration routines and is a starting point
      for the development of a calibration protocol to generate spectrometer
      independent Raman spectra. The presented routine ensures that a chemometric model
      utilizes only Raman information of the sample and not artifacts from small shifts
      in the excitation wavelength. This is crucial for the application of Raman
      spectroscopy in real-world-settings, such as diagnostics of diseases or
      identification of bacteria. 

PMID- 25978025
TI  - Crystal-surface-induced simultaneous synthesis and hierarchical morphogenesis of
      conductive polymers.
AB  - The surface of oxidant crystals facilitates the simultaneous synthesis and
      morphogenesis of conductive polymer materials. Oxidant crystals as a condensed
      phase of the oxidative agent induce the formation of the conductive polymer
      nanoparticles and their accumulated films. 

PMID- 25978024
TI  - Ullrich-Turner Syndrome and Tumor Risk: Is There Another Chance to Early
      Gonadectomy in Positive TSPY and SRY Patients?
AB  - The presence of the Y chromosome in the karyotype of patients with disorders of
      sex differentiation is significantly associated with an increased risk to develop
      specific types of malignancies, predominantly type II germ cell tumors (GCTs).
      Gonadoblastoma in the gonads without an obvious testicular differentiation and
      intratubular germ cell neoplasia of unclassified type in testicular tissue are
      the precursor lesions of most GCTs. Gonadal dysgenesis, the characteristic
      feature of Ullrich-Turner syndrome (UTS), further contributes to increase this
      tumor risk. The reported incidence of Y chromosome material in UTS is 6 to 8% and
      in these cases an early gonadectomy is strongly recommended to prevent the risk
      of a malignancy. The aim of this work was to retrospectively analyze the clinical
      outcome and the histopathological and cytogenetic findings of our UTS patients
      who underwent gonadectomy to establish strict selection criteria aimed at
      promoting an organ-sparing surgery. 

PMID- 25978026
TI  - Mechanistic insights into the synergistic catalysis by Au(I), Ga(III), and
      counterions in the Nakamura reaction.
AB  - A computational study based on density functional theory (DFT) establishes the
      mechanisms for synergistic Au/Ga catalyzed addition of unactivated terminal
      alkynes to dicarbonyls, the Nakamura reaction. The role played by each of the
      metal catalysts and the counterion in the reaction has been elucidated. It has
      been shown that the triazole (TA) ligand could specifically activate the
      formation of a particular regioisomer through strong non-covalent interactions.
      Calculated regioselectivities and activation free energies are in excellent
      agreement with the experimental results. Observed regioselectivities were
      rationalized employing a distortion interaction analysis which suggests that the
      interaction between metal activated reactant fragments in the transition state
      geometries is a major factor that contributes to the overall barrier height and
      selectivity. Such enhanced preference for the reaction at the alkyl/aryl
      substituted carbon of alkynes was strongly influenced by the additional non
      covalent interactions exerted by the TA ligand. Excellent agreement between the
      calculations using a homogeneous gold complex as the catalyst and experimentally
      observed kinetics and selectivity negates the role of in situ formed gold
      clusters in the Nakamura reaction. 

PMID- 25978027
TI  - PBRM1 suppresses bladder cancer by cyclin B1 induced cell cycle arrest.
AB  - Growing evidence indicates that dys-regulation of PBRM1 contributes to
      tumorigenesis. However, little is known about the biological function of PBRM1 in
      the development or progression of bladder cancer. In this study, we aimed to
      elucidate the pathophysiological role of PBRM1 in bladder cancer. We assessed the
      expression of PBRM1 in 64 bladder cancer tissue samples with matching normal
      tissues. We explored the biological functions of PBRM1 both in vitro and in vivo.
      Mutational status of PBRM1 was analyzed. Effect of PBRM1 on cell cycle was
      evaluated. qRT-PCR and Western blot were carried out to evaluate the expression
      of cyclins affected by PBRM1. Our results showed that PBRM1 expression was
      significantly reduced in bladder cancer cells and tissues compared to their
      normal counterparts. The reduced expression of PBRM1 was associated with advanced
      tumor stage, low differentiation grade and worse patient outcome. Further
      functional analysis demonstrated that PBRM1 suppressed bladder cancer cell
      proliferation, migration, colony formation in vitro and tumorigenicity in vivo.
      Genetic alteration analysis showed no amino-acid sequence altering mutations. We
      found that PBRM1 could block the G2/M transition by repressing cyclin B1. Our
      data indicated that PBRM1 functions as a tumor suppressor in bladder cancer by
      repressing cyclin B1 expression.

PMID- 25978028
TI  - Gap junctions modulate glioma invasion by direct transfer of microRNA.
AB  - The invasiveness of high-grade glioma is the primary reason for poor survival
      following treatment. Interaction between glioma cells and surrounding astrocytes
      are crucial to invasion. We investigated the role of gap junction mediated miRNA
      transfer in this context. By manipulating gap junctions with a gap junction
      inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that
      functional glioma-glioma gap junctions suppress glioma invasion while glioma
      astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro
      transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions
      are permeable to microRNA, we compared the microRNA profiles of astrocytes before
      and after co-culture with glioma cells, identifying specific microRNAs as
      candidates for transfer through gap junctions from glioma cells to astrocytes.
      Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes
      is through gap junctions; this transfer is responsible, in part, for the pro
      invasive effect. Our results establish a role for glioma-astrocyte gap junction
      mediated microRNA signaling in modulation of glioma invasive behavior, and that
      gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our
      findings reveal the potential for therapeutic interventions based on abolishing
      alteration of stromal cells by tumor cells via manipulation of microRNA and gap
      junction channel activity. 

PMID- 25978031
TI  - ROS1 amplification mediates resistance to gefitinib in glioblastoma cells.
AB  - Glioblastoma (GBM) is the most aggressive brain tumor in adults and remains
      incurable despite multimodal intensive treatment regimens. The majority of GBM
      tumors show a mutated or overexpressed EGFR, however, tumors treated with
      tyrosine kinase inhibitors (TKIs) will inevitably recur highlighting the need to
      identify signalling pathways involved in GBM resistance to these drugs. To this
      end, we treated GBM cells that overexpress EGFR with increasing concentrations of
      gefitinib and isolated resistant clones. These resistant clones were subject to
      RNAseq and the expression of several genes was found to be upregulated. These
      genes are mainly tyrosine kinase receptors and include ROS1, DDR1 and PDGFRA and
      are known to control several downstream targets of EGFR. The upregulation of ROS1
      and DDR1 was confirmed at the protein level by western blot. Treatment with a
      potent and highly specific pyrazole ROS1 inhibitor in ROS1 overexpressing clones
      led to a sensitization of these cells to low concentrations of gefitinib.
      Combined treatment with gefitinib and ROS1 inhibitor induces massive cell death
      by apoptosis following a prolonged S phase cell cycle arrest. Our current study
      led to the discovery of alternative pathways used by GBM cells to evade cell
      death following treatment with gefitinib and identifies new therapeutic targets
      to prevent GBM cell resistance to the drug.

PMID- 25978030
TI  - Hypoxia attenuates the proinflammatory response in colon cancer cells by
      regulating IkappaB.
AB  - Two main features common to all solid tumors are tissue hypoxia and inflammation,
      both of which cause tumor progression, metastasis, therapy resistance and
      increased mortality. Chronic inflammation is associated with increased cancer
      risk, as demonstrated for inflammatory bowel disease patients developing colon
      cancer. However, the interplay between hypoxia and inflammation on the molecular
      level remains to be elucidated. We found that MC-38 mouse colon cancer cells
      contain functional hypoxic (HIF-1alpha) and inflammatory (p65/RelA) signaling
      pathways. In contrast to cells of the myeloid lineage, HIF-1alpha levels remained
      unaffected in MC-38 cells treated with LPS, and hypoxia failed to induce NF
      kappaB. A similar regulation of canonical HIF and NF-kappaB target genes
      confirmed these results. RNA deep sequencing of HIF-1alpha and p65/RelA knock
      down cells revealed that a surprisingly large fraction of HIF target genes
      required p65/RelA for hypoxic regulation and a number of p65/RelA target genes
      required HIF-1alpha for proinflammatory regulation, respectively. Hypoxia
      attenuated the inflammatory response to LPS by inhibiting nuclear translocation
      of p65/RelA independently of HIF-1alpha, which was associated with enhanced
      IkappaBalpha levels and decreased IKKbeta phosphorylation. These data demonstrate
      that the interaction between hypoxic and inflammatory signaling pathways needs to
      be considered when designing cancer therapies targeting HIF or NF-kappaB.

PMID- 25978029
TI  - Tie-2 regulates the stemness and metastatic properties of prostate cancer cells.
AB  - Ample evidence supports that prostate tumor metastasis originates from a rare
      population of cancer cells, known as cancer stem cells (CSCs). Unfortunately,
      little is known about the identity of these cells, making it difficult to target
      the metastatic prostate tumor. Here, for the first time, we report the
      identification of a rare population of prostate cancer cells that express the Tie
      2 protein. We found that this Tie-2High population exists mainly in prostate
      cancer cell lines that are capable of metastasizing to the bone. These cells not
      only express a higher level of CSC markers but also demonstrate enhanced
      resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of
      the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC
      markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an
      autocrine loop for the maintenance of prostate CSCs. More importantly, we found
      that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low
      population to both osteoblasts and endothelial cells. Moreover, only the Tie
      2High, but not the Tie-2Low cells developed tumor metastasis in vivo when
      injected at a low number. Taken together, our data suggest that Tie-2 may play an
      important role during the development of prostate tumor metastasis. 

PMID- 25978032
TI  - Novel roles of TMEM100: inhibition metastasis and proliferation of hepatocellular
      carcinoma.
AB  - Transmembrane protein 100 (TMEM100) was activated by ALK1/TGF-beta signaling. We
      found that TMEM100 was decreased in hepatocellular carcinoma (HCC) tissues and in
      highly metastatic cell lines. Overexpressed of TMEM100 inhibited invasion,
      migration and proliferation. Low levels of TMEM100 were associated with
      cirrhosis, tumor size, Tumor nodule number, TNM stage, BCLC stage, Edmondson
      Steiner Stage and vein invasion. Furthermore, TMEM100 was an independent risk
      factor for overall survival (P = 0.03) and disease-free survival (P = 0.019). The
      current findings suggest that TMEM100 functions as a tumor suppressor in HCC
      metastasis and proliferation. 

PMID- 25978033
TI  - Female sex is associated with delayed reperfusion by percutaneous coronary
      intervention in patients with ST-segment elevation myocardial infarction.

PMID- 25978034
TI  - Differential responses to woodland character and landscape context by cryptic
      bats in urban environments.
AB  - Urbanisation is one of the most dramatic forms of land use change which
      relatively few species can adapt to. Determining how and why species respond
      differently to urban habitats is important in predicting future biodiversity loss
      as urban areas rapidly expand. Understanding how morphological or behavioural
      traits can influence species adaptability to the built environment may enable us
      to improve the effectiveness of conservation efforts. Although many bat species
      are able to exploit human resources, bat species richness generally declines with
      increasing urbanisation and there is considerable variation in the responses of
      different bat species to urbanisation. Here, we use acoustic recordings from two
      cryptic, and largely sympatric European bat species to assess differential
      responses in their use of fragmented urban woodland and the surrounding urban
      matrix. There was a high probability of P. pygmaeus activity relative to P.
      pipistrellus in woodlands with low clutter and understory cover which were
      surrounded by low levels of built environment. Additionally, the probability of
      recording P. pygmaeus relative to P. pipistrellus was considerably higher in
      urban woodland interior or edge habitat in contrast to urban grey or non-wooded
      green space. These results show differential habitat use occurring between two
      morphologically similar species; whilst the underlying mechanism for this
      partitioning is unknown it may be driven by competition avoidance over foraging
      resources. Their differing response to urbanisation indicates the difficulties
      involved when attempting to assess how adaptable a species is to urbanisation for
      conservation purposes. 

PMID- 25978035
TI  - Correction: BuShenYiQi Granule Inhibits Atopic Dermatitis via Improving Central
      and Skin Hypothalamic -Pituitary -Adrenal Axis Function.

PMID- 25978036
TI  - Pectate lyase pollen allergens: sensitization profiles and cross-reactivity
      pattern.
AB  - BACKGROUND: Pollen released by allergenic members of the botanically unrelated
      families of Asteraceae and Cupressaceae represent potent elicitors of respiratory
      allergies in regions where these plants are present. As main allergen sources the
      Asteraceae species ragweed and mugwort, as well as the Cupressaceae species,
      cypress, mountain cedar, and Japanese cedar have been identified. The major
      allergens of all species belong to the pectate lyase enzyme family. Thus, we
      thought to investigate cross-reactivity pattern as well as sensitization
      capacities of pectate lyase pollen allergens in cohorts from distinct geographic
      regions. METHODS: The clinically relevant pectate lyase pollen allergens Amb a 1,
      Art v 6, Cup a 1, Jun a 1, and Cry j 1 were purified from aqueous pollen
      extracts, and patients' sensitization pattern of cohorts from Austria, Canada,
      Italy, and Japan were determined by IgE ELISA and cross-inhibition experiments.
      Moreover, we performed microarray experiments and established a mouse model of
      sensitization. RESULTS: In ELISA and ELISA inhibition experiments specific
      sensitization pattern were discovered for each geographic region, which reflected
      the natural allergen exposure of the patients. We found significant cross
      reactivity within Asteraceae and Cupressaceae pectate lyase pollen allergens,
      which was however limited between the orders. Animal experiments showed that
      immunization with Asteraceae allergens mainly induced antibodies reactive within
      the order, the same was observed for the Cupressaceae allergens. Cross-reactivity
      between orders was minimal. Moreover, Amb a 1, Art v 6, and Cry j 1 showed in
      general higher immunogenicity. CONCLUSION: We could cluster pectate lyase
      allergens in four categories, Amb a 1, Art v 6, Cup a 1/Jun a 1, and Cry j 1,
      respectively, at which each category has the potential to sensitize predisposed
      individuals. The sensitization pattern of different cohorts correlated with
      pollen exposure, which should be considered for future allergy diagnosis and
      therapy.

PMID- 25978037
TI  - Premature expression of Foxp3 in double-negative thymocytes.
AB  - Peripheral immune regulation depends on the generation of thymic-derived
      regulatory T (tTreg) cells to maintain self-tolerance and to counterbalance
      overshooting immune responses. The expression of the Treg lineage defining
      transcription factor Foxp3 in developing tTreg cells depends on TCR signaling
      during the thymic selection process of these T cells. In this study, we
      surprisingly identify Foxp3+ immature thymocytes at the double-negative (DN)
      stage in transcription factor 7 (Tcf7)-deficient mice. These Foxp3+ cells did not
      express a TCR (beta or gammadelta chains), CD3 or CD5 and therefore these cells
      were true DN cells. Further investigation of this phenomenon in a transgenic TCR
      model showed that Foxp3-expressing DN cells could not respond to TCR stimulation
      in vivo. These data suggest that Foxp3 expression in these DN cells occurred
      independently of TCR signaling. Interestingly, these Foxp3+ DN cells were located
      in a transition state between DN1 and DN2 (CD4-CD8-CD3-TCR-CD44highCD25low). Our
      results indicate that Tcf7 is involved in preventing the premature expression of
      Foxp3 in DN thymocytes. 

PMID- 25978038
TI  - Modes of Escherichia coli Dps Interaction with DNA as Revealed by Atomic Force
      Microscopy.
AB  - Multifunctional protein Dps plays an important role in iron assimilation and a
      crucial role in bacterial genome packaging. Its monomers form dodecameric
      spherical particles accumulating ~400 molecules of oxidized iron ions within the
      protein cavity and applying a flexible N-terminal ends of each subunit for
      interaction with DNA. Deposition of iron is a well-studied process by which cells
      remove toxic Fe2+ ions from the genetic material and store them in an easily
      accessible form. However, the mode of interaction with linear DNA remained
      mysterious and binary complexes with Dps have not been characterized so far. It
      is widely believed that Dps binds DNA without any sequence or structural
      preferences but several lines of evidence have demonstrated its ability to
      differentiate gene expression, which assumes certain specificity. Here we show
      that Dps has a different affinity for the two DNA fragments taken from the dps
      gene regulatory region. We found by atomic force microscopy that Dps
      predominantly occupies thermodynamically unstable ends of linear double-stranded
      DNA fragments and has high affinity to the central part of the branched DNA
      molecule self-assembled from three single-stranded oligonucleotides. It was
      proposed that Dps prefers binding to those regions in DNA that provide more
      contact pads for the triad of its DNA-binding bundle associated with one vertex
      of the protein globule. To our knowledge, this is the first study revealed the
      nucleoid protein with an affinity to branched DNA typical for genomic regions
      with direct and inverted repeats. As a ubiquitous feature of bacterial and
      eukaryotic genomes, such structural elements should be of particular care, but
      the protein system evolutionarily adapted for this function is not yet known, and
      we suggest Dps as a putative component of this system. 

PMID- 25978039
TI  - The influence of genetic variability and proinflammatory status on the
      development of bone disease in patients with Gaucher disease.
AB  - Gaucher disease, the most common lysosomal storage disorder, is caused by beta
      glucocerebrosidase deficiency. Bone complications are the major cause of
      morbidity in patients with type 1 Gaucher disease (GD1). Genetic components
      strongly influence bone remodelling. In addition, chronic inflammation produced
      by Gaucher cells induces the production of several cytokines, which leads to
      direct changes in the bone remodelling process and can also affect the process
      indirectly through other immune cells. In this study, we analysed the association
      between bone mineral density (BMD), bone marrow burden score, and relevant
      genetic polymorphisms related to bone metabolism, as well as profiles of
      proinflammatory cytokines in a GD1 cohort. This study included 83 patients
      distributed according to bone status. BMD was measured with DXA and broadband
      ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also
      analysed 26 SNPs located in 14 genes related to bone metabolism. To assess
      proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1alpha,
      MIP-1beta, and TNFalpha in plasma samples from 71 control participants and GD1
      patients. SNP genotype proportions and BMD differed significantly between ESRI
      c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant
      associations between GD1 genotypes and bone affectation. When patients were
      stratified by spleen status, we observed significant correlations between non
      /splenectomized groups and Spanish MRI (S-MRI) score. Across genotype proportions
      of non-/splenectomized patients and S-MRI, we observed significant differences in
      ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We
      observed different significant proinflammatory profiles between control
      participants, treatment-naive patients, and patients on enzyme replacement
      therapy (ERT); between non-/splenectomized patients (between untreated and ERT
      treated patients) and among those with differing GBA genotypes. The data suggest
      that patients with GD1 have increased susceptibility to developing bone disease
      owing to the coexistence of genetic variants, and that genetic background in GD1
      is fundamental to regulate the impact of proinflammatory status on the
      development of bone disease. 

PMID- 25978040
TI  - Variation in the Ovine Abomasal Lymph Node Transcriptome between Breeds Known to
      Differ in Resistance to the Gastrointestinal Nematode.
AB  - Texel lambs are known to be more resistant to gastrointestinal nematode (GIN)
      infection than Suffolk lambs, with a greater ability to limit infection. The
      objectives of this study were to: 1) profile the whole transcriptome of abomasal
      lymph node tissue of GIN-free Texel and Suffolk lambs; 2) identify differentially
      expressed genes and characterize the immune-related biological pathways and
      networks associated with these genes. Abomasal lymph nodes were collected from
      Texel (n = 6) and Suffolk (n = 4) lambs aged 19 weeks that had been GIN-free
      since 6 weeks of age. Whole transcriptome profiling was performed using RNA-seq
      on the Illumina platform. At the time of conducting this study, a well annotated
      Ovine genome was not available and hence the sequence reads were aligned with the
      Bovine (UMD3.1) genome. Identification of differentially expressed genes was
      followed by pathway and network analysis. The Suffolk breed accounted for
      significantly more of the differentially expressed genes, (276 more highly
      expressed in Suffolk v 162 in Texel; P < 0.001). The four most significant
      differentially expressed pathways were all related to immunity and were
      classified as: Role of Pattern Recognition Receptors in Recognition of Bacteria
      and Viruses, Activation of IRF by Cytosolic Pattern Recognition Receptors, Role
      of RIG-I-like Receptors in Antiviral Innate Immunity, and Interferon Signaling.
      Of significance is the fact that all of these four pathways were more highly
      expressed in the Suffolk. These data suggest that in a GIN-free environment,
      Suffolk lambs have a more active immune profile relative to the Texel: this
      immune profile may contribute to the poorer efficiency of response to a GIN
      challenge in the Suffolk breed compared to the Texel breed. 

PMID- 25978041
TI  - The AIRE -230Y Polymorphism Affects AIRE Transcriptional Activity: Potential
      Influence on AIRE Function in the Thymus.
AB  - BACKGROUND: The autoimmune regulator (AIRE) is expressed in the thymus,
      particularly in thymic medullary epithelial cells (mTECs), and is required for
      the ectopic expression of a diverse range of peripheral tissue antigens by mTECs,
      facilitating their ability to perform negative selection of auto-reactive
      immature T-cells. The expression profile of peripheral tissue antigens is
      affected not only by AIRE deficiency but also with variation of AIRE activity in
      the thymus. METHOD AND RESULTS: Therefore we screened 591bp upstream of the AIRE
      transcription start site including AIRE minimal promoter for single nucleotide
      polymorphism (SNPs) and identified two SNPs -655R (rs117557896) and -230Y
      (rs751032) respectively. To study the effect of these variations on AIRE promoter
      activity we generated a Flp-In host cell line which was stably transfected with a
      single copy of the reporter vector. Relative promoter activity was estimated by
      comparing the luciferase specific activity for lysates of the different reporter
      AIRE promoter-reporter gene constructs including AIRE-655G AIRE-230C, AIRE-655G
      AIRE-230T and AIRE-655A AIRE-230C. The analysis showed that the commonest
      haplotype AIRE-655G AIRE-230C has the highest luciferase specific activity
      (p<0.001). Whereas AIRE-655G AIRE-230T has a luciferase specific activity value
      that approaches null. Both AIRE promoter polymorphic sites have one allele that
      forms a CpG methylation site which we determined can be methylated in methylation
      assays using the M.SssI CpG methyltransferase. CONCLUSION: AIRE-230Y is in a
      conserved region of the promoter and is adjacent to a predicted WT1 transcription
      factor binding site, suggesting that AIRE-230Y affects AIRE expression by
      influencing the binding of biochemical factors to this region. Our findings show
      that AIRE-655GAIRE-230T haplotype could dramatically alter AIRE transcription and
      so have an effect on the process of negative selection and affect susceptibility
      to autoimmune conditions.

PMID- 25978042
TI  - Quantitative Assessment of the Influence of Rhizoma Zingiberis on the Level of
      Aconitine in Rat Gut Sacs and Qualitative Analysis of the Major Influencing
      Components of Rhizoma Zingiberis on Aconitine Using UPLC/MS.
AB  - This study attempted to clarify the material basis for the detoxification of
      Rhizoma Zingiberis (RZ) on aconitine, an analgesic drug, by quantitatively
      assessing the influence of RZ on the in vitro intestinal concentration of
      aconitine using an everted gut sac model and by qualitatively identifying the
      components in the RZ extract. To quantify aconitine in rat everted gut sacs, both
      an accurate processing method and a sensitive detection method were required. We
      developed a three-step sample processing method to protect the components from
      decomposition and applied ultra-performance liquid chromatography coupled with
      triple quadrupole mass spectrometry (UPLC/TQMS) to quantify aconitine, glucose
      and digoxin. In addition, ultra-performance liquid chromatography coupled with
      linear ion trap mass spectrometry (UPLC/ITMS) was applied to detect the potential
      antidotal components in the RZ extract. Finally, the RZ extract reduced the level
      of aconitine in everted gut sacs, and eleven gingerols were successfully
      identified, which could be considered potential antidotal components for
      aconitine. This study demonstrated the application of two UPLC/MS methods for
      analyzing the material basis for the reciprocity between Chinese medicine
      components in everted gut sacs. 

PMID- 25978045
TI  - Correction: Avoidant Personality Disorder versus Social Phobia: The Significance
      of Childhood Neglect.

PMID- 25978044
TI  - Subunits of the Pyruvate Dehydrogenase Cluster of Mycoplasma pneumoniae Are
      Surface-Displayed Proteins that Bind and Activate Human Plasminogen.
AB  - The dual role of glycolytic enzymes in cytosol-located metabolic processes and in
      cell surface-mediated functions with an influence on virulence is described for
      various micro-organisms. Cell wall-less bacteria of the class Mollicutes
      including the common human pathogen Mycoplasma pneumoniae possess a reduced
      genome limiting the repertoire of virulence factors and metabolic pathways. After
      the initial contact of bacteria with cells of the respiratory epithelium via a
      specialized complex of adhesins and release of cell-damaging factors, surface
      displayed glycolytic enzymes may facilitate the further interaction between host
      and microbe. In this study, we described detection of the four subunits of
      pyruvate dehydrogenase complex (PDHA-D) among the cytosolic and membrane
      associated proteins of M. pneumoniae. Subunits of PDH were cloned, expressed and
      purified to produce specific polyclonal guinea pig antisera. Using colony
      blotting, fractionation of total proteins and immunofluorescence experiments, the
      surface localization of PDHA-C was demonstrated. All recombinant PDH subunits are
      able to bind to HeLa cells and human plasminogen. These interactions can be
      specifically blocked by the corresponding polyclonal antisera. In addition, an
      influence of ionic interactions on PDHC-binding to plasminogen as well as of
      lysine residues on the association of PDHA-D with plasminogen was confirmed. The
      PDHB subunit was shown to activate plasminogen and the PDHB-plasminogen complex
      induces degradation of human fibrinogen. Hence, our data indicate that the
      surface-associated PDH subunits might play a role in the pathogenesis of M.
      pneumoniae infections by interaction with human plasminogen. 

PMID- 25978046
TI  - Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which
      Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.
AB  - The aim of this study was to evaluate the safety, tolerability and
      pharmacokinetics of single dose of Melissa officinalis extract which contained
      rosmarinic acid, including food-effects in healthy individuals. A total of eleven
      healthy individuals were randomly assigned to treatment arms in the two studies
      [Study 1 (fasted state) and Study 2 (fed state)]. Rosmarinic acid in serum was
      measured by a coulometric detection method using High-Performance Liquid
      Chromatography electrochemical detector. The serum concentration of total
      rosmarinic acid peaked at 1 hour after administration of Melissa officinalis
      extract containing 500mg rosmarinic acid in fasted state, with a maximum serum
      concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid
      was calculated from the serum concentration-time profile to be 832.13 nmol *
      hour/ L. Food intake increases area under the curve and delayed time at which the
      maximum serum concentration. Rosmarinic acid supplementation did not affect
      liver, kidney, or blood cell function parameters. No adverse event was reported
      by any of the participants due to the study treatment. Single dose of Melissa
      officinalis extract containing 500 mg rosmarinic acid appears to be safe and
      tolerable in healthy individuals. Food intake increased the exposure of
      rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

PMID- 25978043
TI  - Cardiac development in zebrafish and human embryonic stem cells is inhibited by
      exposure to tobacco cigarettes and e-cigarettes.
AB  - BACKGROUND: Maternal smoking is a risk factor for low birth weight and other
      adverse developmental outcomes. OBJECTIVE: We sought to determine the impact of
      standard tobacco cigarettes and e-cigarettes on heart development in vitro and in
      vivo. METHODS: Zebrafish (Danio rerio) were used to assess developmental effects
      in vivo and cardiac differentiation of human embryonic stem cells (hESCs) was
      used as a model for in vitro cardiac development. RESULTS: In zebrafish, exposure
      to both types of cigarettes results in broad, dose-dependent developmental
      defects coupled with severe heart malformation, pericardial edema and reduced
      heart function. Tobacco cigarettes are more toxic than e-cigarettes at comparable
      nicotine concentrations. During cardiac differentiation of hESCs, tobacco smoke
      exposure results in a delayed transition through mesoderm. Both types of
      cigarettes decrease expression of cardiac transcription factors in cardiac
      progenitor cells, suggesting a persistent delay in differentiation. In definitive
      human cardiomyocytes, both e-cigarette- and tobacco cigarette-treated samples
      showed reduced expression of sarcomeric genes such as MLC2v and MYL6.
      Furthermore, tobacco cigarette-treated samples had delayed onset of beating and
      showed low levels and aberrant localization of N-cadherin, reduced myofilament
      content with significantly reduced sarcomere length, and increased expression of
      the immature cardiac marker smooth muscle alpha-actin. CONCLUSION: These data
      indicate a negative effect of both tobacco cigarettes and e-cigarettes on heart
      development in vitro and in vivo. Tobacco cigarettes are more toxic than E
      cigarettes and exhibit a broader spectrum of cardiac developmental defects.

PMID- 25978048
TI  - Correction: Why Is Aging Conserved and What Can We Do about it?
AB  - [This corrects the article DOI: 10.1371/journal.pbio.1002131.]. 

PMID- 25978047
TI  - Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with
      the Immunopathology of Chagas Disease.
AB  - The aim of this study was to investigate the influence of killer cell
      immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA)
      ligands in the susceptibility of chronic Chagas disease. This case-control study
      enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72
      women, mean age of 60.4 +/- 9.8 years) treated at the University Hospital of
      Londrina and the Chagas Disease Laboratory of the State University of Maringa. A
      control group was formed of 165 healthy individuals - spouses of patients or
      blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a
      mean age of 59.0 +/- 11.4 years). Genotyping of HLA and KIR was performed by PCR
      SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent
      in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those
      who manifested chronic chagasic cardiopathy-CCC (P = 0.0002; Pc = 0.0004; OR =
      6.64; 95% CI = 2.30-18.60) when compared to the control group, and when CCC group
      was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR
      = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively
      associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to
      immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating
      receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk
      factor in the chronic Chagas disease and chronic chagasic cardiopathy. 

PMID- 25978049
TI  - Methanesulfonate (MSA) Catabolic Genes from Marine and Estuarine Bacteria.
AB  - Quantitatively, methanesulfonate (MSA) is a very relevant compound in the global
      biogeochemical sulfur cycle. Its utilization by bacteria as a source of carbon
      and energy has been described and a specific enzyme, methanesulfonate
      monooxygenase (MSAMO), has been found to perform the first catabolic step of its
      oxidation. Other proteins seemingly involved in the import of MSA into bacterial
      cells have been reported. In this study, we obtained novel sequences of genes
      msmA and msmE from marine, estuary and soil MSA-degraders (encoding the large
      subunit of the MSAMO enzyme and the periplasmic component of the import system,
      respectively). We also obtained whole-genome sequences of two novel marine
      Filomicrobium strains, Y and W, and annotated two full msm operons in these
      genomes. Furthermore, msmA and msmE sequences were amplified from North Atlantic
      seawater and analyzed. Good conservation of the MsmA deduced protein sequence was
      observed in both cultured strains and metagenomic clones. A long spacer sequence
      in the Rieske-type [2Fe-2S] cluster-binding motif within MsmA was found to be
      conserved in all instances, supporting the hypothesis that this feature is
      specific to the large (alpha) subunit of the MSAMO enzyme. The msmE gene was more
      difficult to amplify, from both cultivated isolates and marine metagenomic DNA.
      However, 3 novel msmE sequences were obtained from isolated strains and one
      directly from seawater. With both genes, our results combined with previous
      metagenomic analyses seem to imply that moderate to high-GC strains are somehow
      favored during enrichment and isolation of MSA-utilizing bacteria, while the
      majority of msm genes obtained by cultivation-independent methods have low levels
      of GC%, which is a clear example of the misrepresentation of natural populations
      that culturing, more often than not, entails. Nevertheless, the data obtained in
      this work show that MSA-degrading bacteria are abundant in surface seawater,
      which suggests ecological relevance for this metabolic group of bacteria. 

PMID- 25978050
TI  - RADIOLOGY OF THE MONTH: Vocal Cord Dysfunction with Multiple Cranial
      Neuropathies.
AB  - A 67-year-old female presented to our institution with a progressive history of
      hoarseness for the past six months. The patient also referred shoulder weakness
      and cough during the same period of time. She denied weight loss and tobacco use.
      Past medical history was negative for squamous cell carcinoma of the head and
      neck region. Physical examination demonstrated asymmetry of the
      sternocleidomastoid and trapezius muscles. Flexible laryngoscopy was performed
      and revealed complete unilateral vocal cord paralysis on the right. Magnetic
      Resonance (MR) of the brain with intravenous contrast (Figure 1) and computer
      tomography (CT) of soft tissue of the neck with contrast (Figure 2) were
      performed for further evaluation. 

PMID- 25978051
TI  - CLINICAL CASE OF THE MONTH: A Review of Situs Inversus and Dextrocardia.
AB  - A 21-year-old woman at 25 weeks gestation presented to the emergency department
      with chief complaints of decreased appetite for one week, fever, runny and stuffy
      nose, and generalized muscle pains. 

PMID- 25978052
TI  - Gastroparesis - a novel cause of persistent thyroid stimulating hormone elevation
      in hypothyroidism.
AB  - Hypothyroidism is easily treated by levothyroxine therapy which has an 80 percent
      absorption rate, mostly in the jejunum. The replacement dose of daily
      levothyroxine is usually calculated at 1.6 mcg/kg body weight per day. We report
      a 77-year-old man who required supraphysiologic thyroxine replacement (>2.7 mcg/
      kg/day) to treat his hypothyroidism. The patient was referred for persistent
      thyroid stimulating hormone (TSH) elevation (40 mcIU/ml) while on 175 mcg of
      levothyroxine. Patient was compliant with medication. Medical history included
      diabetes mellitus type 2, cerebrovascular accident, depression, hypertension,
      hyperlipidemia, atherosclerotic cardiovascular disease, vitamin B12 deficiency,
      Addison's disease, as well as a colostomy secondary to diverticulitis. He was
      taking aspirin, carvedilol, cholecalciferol, finasteride, fluoxetine, furosemide,
      ketoconazole, levothyroxine, prednisone, and albuterol/ipratropium inhaler. His
      height was 180.3 cm; weight, 107 kg. Thyroid was impalpable, and he was
      clinically euthyroid. Despite discontinuation of iron and statin which are known
      to interfere with thyroxine absorption and crushing of thyroxine tablets to
      enhance absorption, his TSH remained elevated. Celiac disease and Helicobacter
      pylori infection were ruled out with serological testing. There was no
      proteinuria and anti-parietal cell antibody was positive. Gastroparesis was
      confirmed by gastric emptying study. He continued to require increasing doses of
      thyroxine with increment to 300 mcg daily. To our knowledge, this is the first
      documented association between gastroparesis and thyroxine malabsorption. We
      recommend that gastroparesis be considered in any patient with persistent TSH
      elevation despite usual thyroxine doses.

PMID- 25978053
TI  - Retroperitoneal immature teratoma.
AB  - Retroperitoneal immature teratoma is a rare tumor in the newborn infant with only
      a few instances reported in several case series.(1,2,3) We report a case of
      retroperitoneal immature teratoma presenting unusually on day one of life with
      severe abdominal distension and respiratory failure. 

PMID- 25978054
TI  - First 1,000 Cases of Gamma Knife Surgery for Various Intracranial Disorders in
      LSU Health-Shreveport: Radiological and Clinical Outcome.
AB  - OBJECTIVE: Gamma knife radiosurgery (GKRS) has emerged as an important
      therapeutic alternative for different intracranial lesions. We have reviewed our
      institution's first 1,000 cases of radiosurgeries. MATERIALS AND METHODS: We
      performed a retrospective review (2000-2013) of 1,017 radiosurgeries in 911
      patients with various intracranial lesions including vestibular schwannoma (82),
      meningioma (136), metastatic brain tumors (298), astrocytoma (49), pituitary
      adenoma (92), arteriovenous malformation (85) and trigeminal neuralgia (169).
      RESULTS: GKRS in different intracranial lesions showed significant variations in
      outcome and complications. Overall, the local tumor growth control for benign and
      malignant tumors was 89 percent and 70 percent respectively. The rate of
      obliteration of arteriovenous malformation nidus was 79 percent. The complete and
      partial relief of pain in the patients with trigeminal neuralgia was 55.6 percent
      and 22.4 percent respectively. CONCLUSION: At recent follow-up, GKRS showed good
      control of different tumor growth, obliteration of AVM nidus and remission of
      trigeminal neuralgia pain, good overall and progression free survival rate,
      possible preservation of neurological functions, lesser number of complications,
      and improvement of quality of life. Therefore, GKRS is an important treatment
      option for patients with different benign intracranial tumors, AVM and trigeminal
      neuralgia. However, GKRS is not effective for recurrent malignant tumors in the
      brain.

PMID- 25978055
TI  - Risk Factors for HIV Acquisition in Urban Latinos and Implications for
      Prevention.
AB  - The risk of HIV in the Latino population in the United States is increasing. This
      population has a disproportionate number of new HIV cases, with the largest
      burden in the seventeen southern states. The purpose of this study is to assess
      risk factors for HIV among HIV-positive Latinos in care in New Orleans,
      Louisiana, through a retrospective chart review. The Chi square test of
      proportions, Student's t-test, and Wilcox rank sum test were used to test
      differences by sex and immigration status. Men were more likely to be
      incarcerated, use drugs, and drink alcohol. Undocumented Latinos were younger and
      had increased language barriers. Legally documented participants were more likely
      to use drugs, have a psychiatric diagnosis, and syphilis. Understanding the
      complex risk factors that surround HIV in the Latino population is useful for the
      development of effective and comprehensive prevention programs. 

PMID- 25978056
TI  - The black widow spider bite: differential diagnosis, clinical manifestations, and
      treatment options.
AB  - Unrecognized and untreated black widow spider bites cause significant pain,
      impairment, and rarely death. The widow venom, a powerful neurotoxin known as a
      latrotoxin, causes muscle pain, diaphoresis, tachycardia, flushing, and
      hypertension. Treatment is usually symptomatic with a combination of opioid
      analgesics and muscle relaxants. If symptom resolution fails, an equine IgG
      antiserum is available, but a high index of clinical suspicion coupled with a
      knowledgeable patient history often allows successful treatment, especially when
      the treating physician possesses awareness of this type of bite and its usual
      course and possible complications. 

PMID- 25978057
TI  - Risk factors for human heartworm infections (dirofilariasis) in the South.
AB  - Human pulmonary dirofilariasis (HPD) is caused by the transmission of infective
      third stage larvae of the canine heartworm, Dirofilaria immitis, during blood
      feeding by several species of infected mosquitoes. Since humans are incidental
      hosts and cannot support the parasite's life cycle, infective larvae die after
      migrating to the pulmonary vascular bed, where an initial subclinical
      inflammatory reaction is typically followed by a single pulmonary granuloma. The
      resulting nodular granuloma is described radiographically as a "coin lesion" that
      resembles a neoplastic lesion, which must be ruled out by invasive lung biopsy.
      Since HPD cases have been reported mainly from regions with high canine heartworm
      prevalence, such as the southern United States (US), the objectives of this
      review were (1) to describe the microbiology of the parasite; (2) to resolve any
      misconceptions regarding the pathophysiology and outcomes of canine versus human
      heartworm infections; (3) to describe the prevalence and parasite burden of
      canine dirofilariasis in the South compared to other areas; (4) to describe the
      prevalence of HPD in the South; (5) to identify the most important species of
      mosquito vectors of dirofilariasis based on seroprevalence rates of infection and
      transmission efficiency; (6) to identify the key risk factors for HPD in the
      South; and (7) to recommend new strategies for the diagnosis, management,
      control, and prevention of HPD. Future investigations should focus on targeting
      specific mosquito species for improved vector control of D. immitis transmission
      and on developing new immunologic and molecular methods for diagnosing HPD and
      eliminating the need for invasive diagnostics for differential diagnosis of
      innocuous, parasitic "coin lesions". 

PMID- 25978058
TI  - A review of adult asthma hospitalizations in Louisiana, 2006-2011.
AB  - This paper examines asthma inpatient hospitalizations for Louisiana residents
      ages 15 years and older from 2006 to 2011. There were 21,398 asthma
      hospitalizations, with 14,401 unique cases. Approximately 22 percent of cases had
      more than one asthma hospitalization. The case rate of adults hospitalized for
      asthma decreased significantly during the six-year period. However, the rate of
      all adult hospitalizations for asthma did not significantly change. Black women
      had the highest age-adjusted case rate, followed by white women. Days
      hospitalized averaged from 2.8 to 4.9 among the youngest to the oldest age
      groups, respectively. Differences between black and white patients were observed
      in type of payment and admit source. Parish rates varied significantly: Caldwell,
      Jefferson Davis, and LaSalle had rates that were at least twice the mean state
      rate. Rural parishes had a significantly higher rate than non-rural parishes. The
      information in this review can be used to target outreach and prevention
      activities. 

PMID- 25978059
TI  - ECG Case of the Month: Unexpected Atrioventricular Conduction in High-Grade
      Atrioventricular Block. 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, Seroquel 25 mg qd, and memantine hydrochloride 10 mg qd. He had
      orthostatic hypotension with supine blood pressure of 173/77 mm Hg 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- 25978060
TI  - PATHOLOGY IMAGE OF THE MONTH: Sudden Cardiac Death Caused by an Uncommon Disease.
AB  - A 57-year-old female, found dead lying supine in bed, was transferred to the
      autopsy service for an unrestricted autopsy to be performed under the
      authorization by the coroner. Medical history was unknown. At the time of
      autopsy, an implantable cardioverter-defibrillator (ICD) was identified in the
      subcutaneous tissues of the left subclavicular chest, with distal leads
      terminating in a small amount of fibrous tissue within the right auricular
      appendage and along the medial wall of the right ventricle. The heart was
      enlarged at 430gm (312 +/-78) and cross sections were notable for left
      ventricular hypertrophy at 1.9cm (1.0-1.5cm) and for dilatation of the right
      ventricular chamber on initial apical cross section. All cross sections, from
      cardiac apex to subvalvular base, showed broad patches of white-yellow myocardial
      discoloration, without obvious hemorrhage, along the free wall of the left
      ventricle, the free wall of the right ventricle, and within the anterior
      interventricular septum (Figure 1). Additional notable findings at autopsy
      included a vena caval filter devoid of thromboembolic material, a patent foramen
      ovale (0.7cm) and microscopic plexogenic arteriopathy, low grade, consistent with
      pulmonary hypertension within the intrapulmonary vasculature. Histology from the
      discolored patches of myocardium is seen in Figure 2. Special stains for
      microorgansims (periodic acid-Schiff, Gomori methanamine silver, and Fite) were
      all negative. 

PMID- 25978062
TI  - EphA4 Regulates the Balance between Self-Renewal and Differentiation of Radial
      Glial Cells and Intermediate Neuronal Precursors in Cooperation with FGF
      Signaling.
AB  - In mouse cerebral corticogenesis, neurons are generated from radial glial cells
      (RGCs) or from their immediate progeny, intermediate neuronal precursors (INPs).
      The balance between self-renewal of these neuronal precursors and specification
      of cell fate is critical for proper cortical development, but the signaling
      mechanisms that regulate this progression are poorly understood. EphA4, a member
      of the receptor tyrosine kinase superfamily, is expressed in RGCs during
      embryogenesis. To illuminate the function of EphA4 in RGC cell fate determination
      during early corticogenesis, we deleted Epha4 in cortical cells at E11.5 or
      E13.5. Loss of EphA4 at both stages led to precocious in vivo RGC differentiation
      toward neurogenesis. Cortical cells isolated at E14.5 and E15.5 from both
      deletion mutants showed reduced capacity for neurosphere formation with greater
      differentiation toward neurons. They also exhibited lower phosphorylation of ERK
      and FRS2alpha in the presence of FGF. The size of the cerebral cortex at P0 was
      smaller than that of controls when Epha4 was deleted at E11.5 but not when it was
      deleted at E13.5, although the cortical layers were formed normally in both
      mutants. The number of PAX6-positive RGCs decreased at later developmental stages
      only in the E11.5 Epha4 deletion mutant. These results suggest that EphA4, in
      cooperation with an FGF signal, contributes to the maintenance of RGC self
      renewal and repression of RGC differentiation through the neuronal lineage. This
      function of EphA4 is especially critical and uncompensated in early stages of
      corticogenesis, and thus deletion at E11.5 reduces the size of the neonatal
      cortex. 

PMID- 25978061
TI  - Immunoproteasome deficiency protects in the retina after optic nerve crush.
AB  - The immunoproteasome is upregulated by disease, oxidative stress, and
      inflammatory cytokines, suggesting an expanded role for the immunoproteasome in
      stress signaling that goes beyond its canonical role in generating peptides for
      antigen presentation. The signaling pathways that are regulated by the
      immunoproteasome remain elusive. However, previous studies suggest a role for the
      immunoproteasome in the regulation of PTEN and NF-kappaB signaling. One well
      known pathway upstream of NF-kappaB and downstream of PTEN is the Akt signaling
      pathway, which is responsible for mediating cellular survival and is modulated
      after optic nerve crush (ONC). This study investigated the role of retinal
      immunoproteasome after injury induced by ONC, focusing on the Akt cell survival
      pathway. Retinas or retinal pigment epithelial (RPE) cells from wild type (WT)
      and knockout (KO) mice lacking either one (LMP2) or two (LMP7 and MECL-1)
      catalytic subunits of the immunoproteasome were utilized in this study. We show
      that mRNA and protein levels of the immunoproteasome subunits are significantly
      upregulated in WT retinas following ONC. Mice lacking the immunoproteasome
      subunits show either a delayed or dampened apoptotic response as well as altered
      Akt signaling, compared to WT mice after ONC. Treatment of the RPE cells with
      insulin growth factor-1 (IGF-1) to stimulate Akt signaling confirmed that the
      immunoproteasome modulates this pathway, and most likely modulates parallel
      pathways as well. This study links the inducible expression of the
      immunoproteasome following retinal injury to Akt signaling, which is important in
      many disease pathways. 

PMID- 25978064
TI  - Medicinal plants recommended by the world health organization: DNA barcode
      identification associated with chemical analyses guarantees their quality.
AB  - Medicinal plants are used throughout the world, and the regulations defining
      their proper use, such as identification of the correct species and verification
      of the presence, purity and concentration of the required chemical compounds, are
      widely recognized. Herbal medicines are made from vegetal drugs, the processed
      products of medicinal species. These processed materials present a number of
      challenges in terms of botanical identification, and according to the World
      Health Organization (WHO), the use of incorrect species is a threat to consumer
      safety. The samples used in this study consisted of the dried leaves, flowers and
      roots of 257 samples from 8 distinct species approved by the WHO for the
      production of medicinal herbs and sold in Brazilian markets. Identification of
      the samples in this study using DNA barcoding (matK, rbcL and ITS2 regions)
      revealed that the level of substitutions may be as high as 71%. Using qualitative
      and quantitative chemical analyses, this study identified situations in which the
      correct species was being sold, but the chemical compounds were not present. Even
      more troubling, some samples identified as substitutions using DNA barcoding
      contained the chemical compounds from the correct species at the minimum required
      concentration. This last situation may lead to the use of unknown species or
      species whose safety for human consumption remains unknown. This study concludes
      that DNA barcoding should be used in a complementary manner for species
      identification with chemical analyses to detect and quantify the required
      chemical compounds, thus improving the quality of this class of medicines. 

PMID- 25978063
TI  - Genotype-Phenotype Correlations in CYP1B1-Associated Primary Congenital Glaucoma
      Patients Representing Two Large Cohorts from India and Brazil.
AB  - BACKGROUND: Primary congenital glaucoma (PCG), occurs due to the developmental
      defects in the trabecular meshwork and anterior chamber angle in children. PCG
      exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated
      worldwide. Despite the diverse mutation spectra, the clinical implications of
      these mutations are yet unclear. The present study attempted to delineate the
      clinical profile of PCG in the background of CYP1B1 mutations from a large cohort
      of 901 subjects from India (n=601) and Brazil (n=300). METHODS: Genotype
      phenotype correlations was undertaken on clinically well characterized PCG cases
      from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1
      mutation on a set of demographic and clinical parameters. The demographic
      (gender, and history of consanguinity) and quantitative clinical (presenting
      intraocular pressure [IOP] and corneal diameter [CD]) parameters were considered
      as binary and continuous variables, respectively, for PCG patients in the
      background of the overall mutation spectra and also with respect to the prevalent
      mutations in India (R368H) and Brazil (4340delG). All these variables were fitted
      in a multivariate logistic regression model using the Akaike Information
      Criterion (AIC) to estimate the adjusted odds ratio (OR) using the R software
      (version 2.14.1). RESULTS: The overall mutation spectrum were similar across the
      Indian and Brazilian PCG cases, despite significantly higher number of homozygous
      mutations in the former (p=0.024) and compound heterozygous mutations in the
      later (p=0.012). A wide allelic heterogeneity was observed and only 6 mutations
      were infrequently shared between these two populations. The adjusted ORs for the
      binary (demographic) and continuous (clinical) variables did not indicate any
      susceptibility to the observed mutations (p>0.05). CONCLUSIONS: The present study
      demonstrated a lack of genotype-phenotype correlation of the demographic and
      clinical traits to CYP1B1 mutations in PCG at presentation. However, the
      susceptibility of these mutations to the long-term progression of these traits
      are yet to be deciphered.

PMID- 25978066
TI  - Altered Fruit and Seed Development of Transgenic Rapeseed (Brassica napus) Over
      Expressing MicroRNA394.
AB  - Fruit and seed development in plants is a complex biological process mainly
      involved in input and biosynthesis of many storage compounds such as proteins and
      oils. Although the basic biochemical pathways for production of the storage
      metabolites in plants are well characterized, their regulatory mechanisms are not
      fully understood. In this study, we functionally identified rapeseed (Brassica
      napus) miR394 with its target gene Brassica napus leaf curling responsiveness
      (BnLCR) to dissect a role of miR394 during the fruit and seed development.
      Transgenic rapeseed plants over-expressing miR394 under the control of the
      cauliflower mosaic virus 35S promoter were generated. miR394 over-expression
      plants exhibited a delayed flowering time and enlarged size of plants, leaf
      blade, pods and seed body, but developed seeds with higher contents of protein
      and glucosinolates (GLS) and lower levels of oil accumulation as compared to wild
      type. Over-expression of miR394 altered the fatty acid (FA) composition by
      increasing several FA species such as C16:0 and C18:0 and unsaturated species of
      C20:1 and C22:1 but lowering C18:3. This change was accompanied by induction of
      genes coding for transcription factors of FA synthesis including leafy cotyledon1
      (BnLEC1), BnLEC2, and FUSCA3 (FUS3). Because the phytohormone auxin plays a
      crucial role in fruit development and seed patterning, the DR5-GUS reporter was
      used for monitoring the auxin response in Arabidopsis siliques and demonstrated
      that the DR5 gene was strongly expressed. These results suggest that BnmiR394 is
      involved in rapeseed fruit and seed development.

PMID- 25978067
TI  - Global value trees.
AB  - The fragmentation of production across countries has become an important feature
      of the globalization in recent decades and is often conceptualized by the term
      "global value chains" (GVCs). When empirically investigating the GVCs, previous
      studies are mainly interested in knowing how global the GVCs are rather than how
      the GVCs look like. From a complex networks perspective, we use the World Input
      Output Database (WIOD) to study the evolution of the global production system. We
      find that the industry-level GVCs are indeed not chain-like but are better
      characterized by the tree topology. Hence, we compute the global value trees
      (GVTs) for all the industries available in the WIOD. Moreover, we compute an
      industry importance measure based on the GVTs and compare it with other network
      centrality measures. Finally, we discuss some future applications of the GVTs. 

PMID- 25978065
TI  - covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the
      Virulence of Group A Streptococcus.
AB  - BACKGROUND: Group A streptococcus (GAS, Streptococcus pyogenes), a multi
      virulent, exclusive human pathogen responsible for various invasive and non
      invasive diseases possesses biofilm forming phenomenon as one of its pathogenic
      armaments. Recently, antibiofilm agents have gained prime importance, since
      inhibiting the biofilm formation is expected to reduce development of antibiotic
      resistance and increase their susceptibility to the host immune cells. PRINCIPAL
      FINDINGS: The current study demonstrates the antibiofilm activity of
      3Furancarboxaldehyde (3FCA), a floral honey derived compound, against GAS
      biofilm, which was divulged using crystal violet assay, light microscopy, and
      confocal laser scanning microscopy. The report is extended to study its effect on
      various aspects of GAS (morphology, virulence, aggregation) at its minimal
      biofilm inhibitory concentration (132MUg/ml). 3FCA was found to alter the growth
      pattern of GAS in solid and liquid medium and increased the rate of auto
      aggregation. Electron microscopy unveiled the increase in extra polymeric
      substances around cell. Gene expression studies showed down-regulation of covR
      gene, which is speculated to be the prime target for the antibiofilm activity.
      Increased hyaluronic acid production and down regulation of srtB gene is
      attributed to the enhanced rate of auto-aggregation. The virulence genes (srv,
      mga, luxS and hasA) were also found to be over expressed, which was manifested
      with the increased susceptibility of the model organism Caenorhabditis elegans to
      3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C.
      elegans. SIGNIFICANCE: Though 3FCA possess antibiofilm activity against GAS, it
      was also found to increase the virulence of GAS. This study demonstrates that,
      covR mediated antibiofilm activity may increase the virulence of GAS. This also
      emphasizes the importance to analyse the acclimatization response and virulence
      of the pathogen in the presence of antibiofilm compounds prior to their clinical
      trials.

PMID- 25978069
TI  - Nickelacyclopentadienylchromium tricarbonyl unit as a bulky pseudohalogen in
      cyclopentadienylchromium complexes leading to low-energy high-spin structures.
AB  - Recent studies, particularly from the laboratory of Buchalski and co-workers,
      have resulted in the syntheses of nickelacyclopentadienyl and nickelafluorenyl
      metallacycles that can function as pentahapto ligands in transition-metal
      complexes, similar to the ubiquitous cyclopentadienyl ligand. The structures and
      energetics of the neutral binuclear chromium carbonyls (CpNiC4H4)2Cr2(CO)n (n =
      6, 5, 4, 3; Cp = eta(5)-C5H5) containing the unsubstituted
      nickelacyclopentadienyl ligand have been investigated by density functional
      theory. The lowest energy (CpNiC4H4)2Cr2(CO)n (n = 6, 4) structures are similar
      to the corresponding experimentally characterized Cp2Cr2(CO)n structures with
      predicted Cr-Cr distances of ~3.22 and ~2.27 A corresponding to the formal single
      and triple bonds, respectively. This gives the chromium atoms, as well as the
      nickel atoms, the favored 18-electron configuration. These species appear to be
      promising synthetic targets. However, the lowest energy (CpNiC4H4)2Cr2(CO)n (n =
      5, 3) structures, as well as two (CpNiC4H4)2Cr2(CO)4 structures ~10 to 12
      kcal/mol in energy above the global minimum, can be dissected into a discrete
      pseudohalogen (CpNiC4H4)Cr(CO)3 unit and a (CpNiC4H4)Cr(CO)n-3 unit linked by a
      Cr-Cr bond flanked by one to three generally weakly semibridging CO groups. In
      most cases, the chromium atoms in the (CpNiC4H4)Cr(CO)n-3 units of these
      structures have 14-16-electron configurations rather than the favored 18-electron
      configuration. This leads to triplet and even quintet spin states in the lowest
      energy structures. 

PMID- 25978070
TI  - Nanoelectrochemical approach to detecting short-lived intermediates of
      electrocatalytic oxygen reduction.
AB  - Development of better catalysts for the oxygen reduction reaction (ORR) and other
      electrocatalytic processes requires detailed knowledge of reaction pathways and
      intermediate species. Here we report a new methodology for detecting charged
      reactive intermediates and its application to the mechanistic analysis of ORR. A
      nanopipette filled with an organic phase that is immiscible with the external
      aqueous solution was used as a tip in the scanning electrochemical microscope to
      detect and identify a short-lived superoxide (O2(?-)) intermediate and to
      determine the rate of its generation at the catalytic Pt substrate and its
      lifetime in neutral aqueous solution. The voltammogram of the O2(?-) anion
      transfer to the organic phase provides a unique signature for unambiguous
      identification of superoxide. The extremely short attainable separation distance
      between the pipette tip and substrate surface (~1 nm) makes this technique
      suitable for detecting and identifying charged intermediates of catalytic
      processes with a lifetime of a few nanoseconds. 

PMID- 25978071
TI  - Chiral resolution capabilities of DNA oligonucleotides.
AB  - Herein, we studied the chiral resolution properties of a repertoire of
      arbitrarily chosen DNA oligonucleotides (ON). Ten oligonucleotidic sequences
      characterized by diverse base compositions, sizes, and structural features,
      ranging from secondary structure-free homo-oligonucleotides to duplex, hairpin,
      and three-way junction architectures, were investigated as potential chiral
      selectors. Their enantioselective features were assessed by using ONs as running
      buffer additives in partial-filling capillary electrophoresis. It was shown that
      all the screened sequences displayed enantiodiscrimination capabilities toward
      small aromatic compounds. Under (sub)millimolar DNA concentration conditions, the
      combination of only three oligonucleotidic sequences provided the chiral
      resolution of around 20 racemates, including drugs, illegal drugs, amino-acids,
      and nucleosides. This work represents the first demonstration of such analyte
      selectivity spectrum for nucleic acid-based chiral separation tools. 

PMID- 25978068
TI  - Molecular-interaction and signaling profiles of AM3677, a novel covalent agonist
      selective for the cannabinoid 1 receptor.
AB  - The cannabinoid 1 receptor (CB1R) is one of the most abundant G protein-coupled
      receptors (GPCRs) in the central nervous system. CB1R involvement in multiple
      physiological processes, especially neurotransmitter release and synaptic
      function, has made this GPCR a prime drug discovery target, and pharmacological
      CB1R activation has been demonstrated to be a tenable therapeutic modality.
      Accordingly, the design and profiling of novel, drug-like CB1R modulators to
      inform the receptor's ligand-interaction landscape and molecular pharmacology
      constitute a prime contemporary research focus. For this purpose, we report
      utilization of AM3677, a designer endocannabinoid (anandamide) analogue
      derivatized with a reactive electrophilic isothiocyanate functionality, as a
      covalent, CB1R-selective chemical probe. The data demonstrate that reaction of
      AM3677 with a cysteine residue in transmembrane helix 6 of human CB1R (hCB1R),
      C6.47(355), is a key feature of AM3677's ligand-binding motif. Pharmacologically,
      AM3677 acts as a high-affinity, low-efficacy CB1R agonist that inhibits forskolin
      stimulated cellular cAMP formation and stimulates CB1R coupling to G protein.
      AM3677 also induces CB1R endocytosis and irreversible receptor internalization.
      Computational docking suggests the importance of discrete hydrogen bonding and
      aromatic interactions as determinants of AM3677's topology within the ligand
      binding pocket of active-state hCB1R. These results constitute the initial
      identification and characterization of a potent, high-affinity, hCB1R-selective
      covalent agonist with utility as a pharmacologically active, orthosteric-site
      probe for providing insight into structure-function correlates of ligand-induced
      CB1R activation and the molecular features of that activation by the native
      ligand, anandamide. 

PMID- 25978072
TI  - Synthesis and Biological Evaluation of Cyclopentaquinoline Derivatives as
      Nonsteroidal Glucocorticoid Receptor Antagonists.
AB  - The steroidal glucocorticoid antagonist mifepristone has been reported to improve
      the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4
      yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d
      (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The
      compound displayed potent in vitro activity, high selectivity over other steroid
      hormone receptors, and significant antidepressant-like activity in vivo. 

PMID- 25978073
TI  - Calorimetric and Light Scattering Investigations of the Transition from Spherical
      to Wormlike Micelles of C14TAB Triggered by Salicylate.
AB  - Although wormlike micelles (WLM) were first described more than 30 years ago,
      many aspects of their formation process are still unclear. Herein, a systematic
      experimental investigation of the process for wormlike micelle (WLM) formation in
      mixtures of tetradecyltrimethylammonium bromide (C14TAB) and salicylate (2
      hydroxybenzoate) was carried out. This system was used as a model to investigate
      the conditions for the formation of the giant aggregate. For comparison, the
      other two isomers of salicylate (3- and 4-hydroxybenzoate) were also
      investigated, once in these cases wormlike micelles are not formed. The studies
      were based on calorimetric titration, static light scattering, and rheological
      measurements. Enthalpy changes upon titration of C14TAB into 2-hydroxybenzoate
      solutions revealed a highly cooperative and exothermic process that was
      associated with micelle growth. The size of the aggregates, obtained by static
      light scattering measurements, confirms the shape transition. In addition, the
      correlation of these two sets of results with measurements of micelle charge
      surface indicates that this transition occurs around the point of charge
      neutralization. 

PMID- 25978074
TI  - Thoracic range of motion, stability, and correlation to imaging-determined
      degeneration.
AB  - OBJECT The degenerative process of the spinal column results in instability
      followed by a progressive loss of segmental motion. Segmental degeneration is
      associated with intervertebral disc and facet changes, which can be quantified.
      Correlating this degeneration with clinical segmental motion has not been
      investigated in the thoracic spine. The authors sought to determine if imaging
      determined degeneration would correlate with native range of motion (ROM) or the
      change in ROM after decompressive procedures, potentially guiding clinical
      decision making in the setting of spine trauma or following decompressive
      procedures in the thoracic spine. METHODS Multidirectional flexibility tests with
      image analysis were performed on thoracic cadaveric spines with intact ib cage.
      Specimens consisted of 19 fresh frozen human cadaveric spines, spanning C-7 to L
      1. ROM was obtained for each specimen in axial rotation (AR), flexion-extension
      (FE), and lateral bending (LB) in the intact state and following laminectomy,
      unilateral facetectomy, and unilateral costotransversectomy performed at either
      T4-5 (in 9 specimens) or T8-9 (in 10 specimens). Image grading of segmental
      degeneration was performed utilizing 3D CT reconstructions. Imaging scores were
      obtained for disc space degeneration, which quantified osteophytes, narrowing,
      and endplate sclerosis, all contributing to the Lane disc summary score. Facet
      degeneration was quantified using the Weishaupt facet summary score, which
      included the scoring of facet osteophytes, narrowing, hypertrophy, subchondral
      erosions, and cysts. RESULTS The native ROM of specimens from T-1 to T-12 (n =
      19) negatively correlated with age in AR (Pearson's r coefficient = -0.42, p =
      0.070) and FE (r = -0.42, p = 0.076). When regional ROM (across 4 adjacent
      segments) was considered, the presence of disc osteophytes negatively correlated
      with FE (r = -0.69, p = 0.012), LB (r = -0.82, p = 0.001), and disc narrowing
      trended toward significance in AR (r = -0.49, p = 0.107). Facet characteristics,
      scored using multiple variables, showed minimal correlation to native ROM (r
      range from -0.45 to +0.19); however, facet degeneration scores at the surgical
      level revealed strong negative correlations with regional thoracic stability
      following decompressive procedures in AR and LB (Weishaupt facet summary score: r
      = -0.52 and r = -0.71; p = 0.084 and p = 0.010, respectively). Disc degeneration
      was not correlated (Lane disc summary score: r = -0.06, p = 0.861). CONCLUSIONS
      Advanced age was the most important determinant of decreasing native thoracic
      ROM, whereas imaging characteristics (T1-12) did not correlate with the native
      ROM of thoracic specimens with intact rib cages. Advanced facet degeneration at
      the surgical level did correlate to specimen stability following decompressive
      procedures, and is likely indicative of the terminal stages of segmental
      degeneration. 

PMID- 25978075
TI  - Intraspinal psammomatous melanotic schwannoma not associated with Carney complex:
      case report.
AB  - The authors present a case of intraspinal malignant psammomatous melanotic
      schwannoma (PMS) not associated with Carney complex and review all reported cases
      not associated with this syndrome. The focus of this review paper is on the
      characteristics of the malignant progression of PMS. A 54-year-old man had a
      history of squamous cell carcinoma of the neck and tonsillar carcinoma. The
      patient's serial CT scanning study showed a mass in the left C-5 foramen. On
      presentation he was neurologically intact. After 18 months, the patient developed
      radiating pain down the left arm with decreased sensation. MRI of the cervical
      spine showed an enhancing 2.1 * 1.5 * 1.9-cm mass in the left C5-6 foramen. A C5
      6 hemilaminectomy was performed with gross-total removal of the tumor. At 3
      months postoperatively, the patient developed new-onset pain and weakness. MRI
      showed a dumbbell-shaped mass in the left C-7 foramen. MRI of the pelvis showed a
      1.4 * 1.0-cm lesion on the right ischium and a 1.1 * 2.8-cm lesion on the right
      inferior pubic ramus. Anterior cervical discectomy of C5-6 and C6-7 with
      corpectomy of C-6 with subtotal resection of the tumor was completed. PMS should
      not be considered a benign tumor because in 41.1% of patients, including the
      patient in this report, the tumor progresses to malignancy. Long-term follow-up
      is needed in these patients. New surgical treatment plans should be considered. 

PMID- 25978076
TI  - Sacroiliac joint motion in patients with degenerative lumbar spine disorders.
AB  - OBJECT Usually additional anchors into the ilium are necessary in long fusion to
      the sacrum for degenerative lumbar spine disorders (DLSDs), especially for adult
      spine deformity. Although the use of anchors is becoming quite common, surgeons
      must always keep in mind that the sacroiliac (SI) joint is mobile and they should
      be aware of the kinematic properties of the SI joint in patients with DLSDs,
      including adult spinal deformity. No previous study has clarified in vivo
      kinematic changes in the SI joint with respect to patient age, sex, or
      parturition status or the presence of DLSDs. The authors conducted a study to
      clarify the mobility and kinematic characteristics of the SI joint in patients
      with DLSDs in comparison with healthy volunteers by using in vivo 3D motion
      analysis with voxel-based registration, a highly accurate, noninvasive method.
      METHODS Thirteen healthy volunteers (the control group) and 20 patients with
      DLSDs (the DLSD group) underwent low-dose 3D CT of the lumbar spine and pelvis in
      3 positions (neutral, maximal trunk flexion, and maximal trunk extension). SI
      joint motion was calculated by computer processing of the CT images (voxel-based
      registration). 3D motion of the SI joint was expressed as both 6 df by Euler
      angles and translations on the coordinate system and a helical axis of rotation.
      The correlation between joint motion and the cross-sectional area of the trunk
      muscles was also investigated. RESULTS SI joint motion during trunk flexion
      extension was minute in healthy volunteers. The mean rotation angles during trunk
      flexion were 0.07 degrees  around the x axis, -0.02 degrees  around the y axis,
      and 0.16 degrees  around the z axis. The mean rotation angles during trunk
      extension were 0.38 degrees  around the x axis, -0.08 degrees  around the y axis,
      and 0.08 degrees  around the z axis. During trunk flexion-extension, the largest
      amount of motion occurred around the x axis. In patients with DLSDs, the mean
      rotation angles during trunk flexion were 0.57 degrees  around the x axis, 0.01
      degrees  around the y axis, and 0.19 degrees  around the z axis. The mean
      rotation angles during trunk extension were 0.68 degrees  around the x axis, 
      0.11 degrees  around the y axis, and 0.05 degrees  around the z axis. Joint
      motion in patients with DLSDs was significantly greater, with greater individual
      difference, than in healthy volunteers. Among patients with DLSDs, women had
      significantly more motion than men did during trunk extension. SI joint motion
      was significantly negatively correlated with the cross-sectional area of the
      trunk muscles during both flexion and extension of the trunk. CONCLUSIONS The
      authors elucidated the mobility and kinematic characteristics of the SI joint in
      patients with DLSDs compared with healthy volunteers for the first time. This
      information is useful for spine surgeons because of the recent increase in
      spinopelvic fusion for the treatment of DLSDs. 

PMID- 25978077
TI  - How the neck affects the back: changes in regional cervical sagittal alignment
      correlate to HRQOL improvement in adult thoracolumbar deformity patients at 2
      year follow-up.
AB  - OBJECT Regional cervical sagittal alignment (C2-7 sagittal vertical axis [SVA])
      has been shown to correlate with health-related quality of life (HRQOL). The
      study objective was to examine the relationship between cervical and
      thoracolumbar alignment parameters with HRQOL among patients with operative and
      nonoperative adult thoracolumbar deformity. METHODS This is a multicenter
      prospective data collection of consecutive patients with adult thoracolumbar
      spinal deformity. Clinical measures of disability included the Oswestry
      Disability Index (ODI), Scoliosis Research Society-22 Patient Questionnaire (SRS
      22), and 36-Item Short-Form Health Survey (SF-36). Cervical radiographic
      parameters were correlated with global sagittal parameters within the
      nonoperative and operative cohorts. A partial correlation analysis was performed
      controlling for C-7 SVA. The operative group was subanalyzed by the magnitude of
      global deformity (C-7 SVA >= 5 cm vs < 5 cm). RESULTS A total of 318 patients
      were included (186 operative and 132 nonoperative). The mean age was 55.4 +/-
      14.9 years. Operative patients had significantly worse baseline HRQOL and
      significantly larger C-7 SVA, pelvic tilt (PT), mismatch between pelvic incidence
      and lumbar lordosis (PI-LL), and C2-7 SVA. The operative patients with baseline C
      7 SVA >= 5 cm had significantly larger C2-7 lordosis (CL), C2-7 SVA, C-7 SVA, PI
      LL, and PT than patients with a normal C-7 SVA. For all patients, baseline C2-7
      SVA and CL significantly correlated with baseline ODI, Physical Component Summary
      (PCS), SRS Activity domain, and SRS Appearance domain. Baseline C2-7 SVA also
      correlated with SRS Pain and SRS Total. For the operative patients with baseline
      C-7 SVA >= 5 cm, the 2-year C2-7 SVA significantly correlated with 2-year Mental
      Component Summary, SRS Mental, SRS Satisfaction, and decreases in ODI. Decreases
      in C2-7 SVA at 2 years significantly correlated with lower ODI at 2 years. Using
      partial correlations while controlling for C-7 SVA, the C2-7 SVA correlated
      significantly with baseline ODI (r = 0.211, p = 0.002), PCS (r = -0.178, p =
      0.009), and SRS Activity (r = -0.145, p = 0.034) for the entire cohort. In the
      subset of operative patients with larger thoracolumbar deformities, the change in
      C2-7 SVA correlated with change in ODI (r = -0.311, p = 0.03). CONCLUSIONS
      Changes in cervical lordosis correlate to HRQOL improvements in thoracolumbar
      deformity patients at 2-year follow-up. Regional cervical sagittal parameters
      such as CL and C2-7 SVA are correlated with clinical measures of regional
      disability and health status in patients with adult thoracolumbar scoliosis. This
      effect may be direct or a reciprocal effect of the underlying global deformities
      on regional cervical alignment. However, the partial correlation analysis,
      controlling for the magnitude of the thoracolumbar deformity, suggests that there
      is a direct effect of cervical alignment on health measures. Improvements in
      regional cervical alignment postoperatively correlated positively with improved
      HRQOL. 

PMID- 25978078
TI  - Mapping occipital bone thickness using computed tomography for safe screw
      placement.
AB  - OBJECT Safe and effective insertion of occipital bone screws requires
      morphological analysis of the occipital bone, which is poorly documented in the
      literature. The authors of this study present morphological data for determining
      the area of screw placement for optimal internal fixation. METHODS The subjects
      of this institutional review board-approved retrospective study were 105
      individuals without head and neck disease who underwent CT imaging at the
      authors' hospital. There were 55 males and 50 females, with a mean age of 57.1
      years (range 20-91 years). Measurements using CT were taken according to a matrix
      of 55 points following a grid with 1-cm spacing based on the external occipital
      protuberance (EOP). RESULTS The maximum thickness of the occipital bone was at
      the level of the EOP at 16.4 mm. Areas with thicknesses > 8 mm were more frequent
      at the EOP and up to 2 cm in all directions, as well as up to 1 cm in all
      directions at a height of 1 cm inferiorly, and up to 3 cm from the EOP
      inferiorly. The male group tended to have a thicker occipital bone than the
      female group, and the differences were significant around the EOP. The ratio of
      the trabecular bone to the occipital bone thickness was > 30% in the central
      region. At positions more than 2 cm laterally, the ratio was < 15%, and the ratio
      gradually decreased further laterally. CONCLUSIONS Screws that are 8 mm long can
      be placed in the area extending 2 cm laterally from the EOP at the level of the
      superior nuchal line and approximately 3 cm inferior to the center. These results
      suggest that it may be possible to effectively insert a screw over a wider area
      than the conventional reference range. 

PMID- 25978079
TI  - Defining the inherent stability of degenerative spondylolisthesis: a systematic
      review.
AB  - OBJECT A range of surgical options exists for the treatment of degenerative
      lumbar spondylolisthesis (DLS). The chosen technique inherently depends on the
      stability of the DLS. Despite a substantial body of literature dedicated to the
      outcome analysis of numerous DLS procedures, no consensus has been reached on
      defining or classifying the disorder with respect to stability or the role that
      instability should play in a treatment algorithm. The purpose of this study was
      to define grades of stability and to develop a guide for deciding on the optimal
      approach in surgically managing patients with DLS. METHODS The authors conducted
      a qualitative systematic review of clinical or biomechanical analyses evaluating
      the stability of and surgical outcomes for DLS for the period from 1990 to 2013.
      Research focused on nondegenerative forms of spondylolisthesis or spinal stenosis
      without associated DLS was excluded. The primary extracted results were clinical
      and radiographic parameters indicative of DLS instability. RESULTS The following
      preoperative parameters are predictors of stability in DLS: restabilization signs
      (disc height loss, osteophyte formation, vertebral endplate sclerosis, and
      ligament ossification), no disc angle change or less than 3 mm of translation on
      dynamic radiographs, and the absence of low-back pain. The validity and magnitude
      of each parameter's contribution can only be determined through appropriately
      powered prospective evaluation in the future. Identifying these parameters has
      allowed for the creation of a preliminary DLS instability classification (DSIC)
      scheme based on the preoperative assessment of DLS stability. CONCLUSIONS Spinal
      stability is an important factor to consider in the evaluation and treatment of
      patients with DLS. Qualitative assessment of the best available evidence revealed
      clinical and radiographic parameters for the creation of the DSIC, a decision aid
      to help surgeons develop a method of preoperative evaluation to better stratify
      DLS treatment options. 

PMID- 25978080
TI  - A hypnotic analogue of clinical confabulation.
AB  - Confabulation-fabricated or distorted memories about oneself-occurs in many
      disorders, but there is no reliable technique for investigating it in the
      laboratory. The authors used hypnosis to model clinical confabulation by giving
      subjects a suggestion for either (a) amnesia for everything that had happened
      since they started university, (b) amnesia for university plus an instruction to
      fill in memory gaps, or (c) confusion about the temporal order of university
      events. They then indexed different types of memory on a confabulation battery.
      The amnesia suggestion produced the most confabulation, especially for personal
      semantic information. Notably, subjects confabulated by making temporal
      confusions. The authors discuss the theoretical implications of this first
      attempt to model clinical confabulation and the potential utility of such
      analogues. 

PMID- 25978081
TI  - Correlates of the multidimensional construct of hypnotizability: paranormal
      belief, fantasy proneness, magical ideation, and dissociation.
AB  - Hypnotizability is a multifaceted construct that may relate to multiple aspects
      of personality and beliefs. This study sought to address 4 known correlates of
      hypnotizability to aid in its understanding. Eighty undergraduates completed the
      Magical Ideation Scale (MIS), the Creative Experiences Questionnaire (CEQ), the
      Australian Sheep-Goat Scale (ASGS), and the Dissociative Experiences Scale (DES)
      and then were administered the Creative Imagination Scale (CIS). All 5 scales
      were significantly correlated. Participants higher in hypnotizability scored
      higher on the CEQ and the MIS. The findings demonstrate the influence of fantasy
      proneness and magical thinking on hypnotizability and support the theory that
      hypnotizability is a complex interaction of multiple traits. 

PMID- 25978082
TI  - Preferences for descriptors of hypnosis: the international point of view.
AB  - Despite the apparently definitive findings of the Christensen (2005) survey of
      published members of the Society for Clinical and Experimental Hypnosis (SCEH),
      disagreement about which term best describes the capacity to experience hypnosis
      and theoretical preference has continued. SCEH, although international,
      represents primarily North Americans. Preferences of international clinicians and
      researchers were inadequately represented, so the authors surveyed preferences
      from attendees of the International Congress of the International Society of
      Hypnosis in 2012 in Bremen, Germany. The term trance, translated as trance
      capacity or trance ability for this study, was overwhelmingly preferred over the
      other options. Hypnosis was recognized as an identifiable state by 88.46% of
      respondents, whereas only 11.54% viewed it as a sociocognitive phenomenon (role
      play, expectancy, etc.). 

PMID- 25978083
TI  - Methylphenidate facilitates hypnotizability in adults with ADHD: a naturalistic
      cohort study.
AB  - Impaired attention may impede learning of adaptive skills in ADHD. While
      manipulations that reduce competition between attentional processes, including
      hypnosis, could boost learning, their feasibility in ADHD is unknown. Because
      hypnotic phenomena rely on attentional mechanisms, the authors aimed to assess
      whether stimulants could enhance hypnotizability in ADHD. In the current study,
      stimulant-naive patients seeking treatment for ADHD-related symptoms were
      assessed with the Stanford Hypnotic Susceptibility Scale (SHSS) at baseline and
      during methylphenidate treatment. Methylphenidate dose and SHSS increase were
      negatively correlated with baseline SHSS scores. Upon reaching effective doses,
      mean SHSS scores increased significantly. All patients who had been poorly
      hypnotizable at baseline demonstrated moderate-to-high hypnotizability at follow
      up. The data support methylphenidate enhancement of hypnotizability in ADHD, thus
      highlighting novel treatment approaches for this disabling disorder. 

PMID- 25978084
TI  - Hungarian norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.
AB  - Hungarian norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A
      (HGSHS:A) are presented. The Hungarian translation of the HGSHS:A was
      administered under standard conditions to 434 participants (190 males, 244
      females) of several professions. In addition to the traditional self-scoring,
      hypnotic behavior was also recorded by trained observers. Female participants
      proved to be more hypnotizable than males and so were psychology students and
      professionals as compared to nonpsychologists. Hypnotizability varied across
      different group sizes. The normative data-including means, standard deviations,
      and indicators of reliability-are comparable with previously published results.
      The authors conclude that measuring observer-scores increases the ecological
      validity of the scale. The Hungarian version of the HGSHS:A seems to be a
      reliable and valid measure of hypnotizability. 

PMID- 25978085
TI  - Factor analysis of the Elkins Hypnotizability Scale.
AB  - Assessment of hypnotizability can provide important information for hypnosis
      research and practice. The Elkins Hypnotizability Scale (EHS) consists of 12
      items and was developed to provide a time-efficient measure for use in both
      clinical and laboratory settings. The EHS has been shown to be a reliable measure
      with support for convergent validity with the Stanford Hypnotic Susceptibility
      Scale, Form C (r = .821, p < .001). The current study examined the factor
      structure of the EHS, which was administered to 252 adults (51.3% male; 48.7%
      female). Average time of administration was 25.8 minutes. Four factors selected
      on the basis of the best theoretical fit accounted for 63.37% of the variance.
      The results of this study provide an initial factor structure for the EHS. 

PMID- 25978086
TI  - Dissociation and the experience of channeling: narratives of Israeli women who
      practice channeling.
AB  - "Channeling" is a phenomenon in which people describe themselves as receiving
      messages from another personality or dimension of reality. Channeling is often
      regarded as dissociation, which is a disruption in the usually integrated
      functions of consciousness, memory, identity, or perception. This study explored
      the interface between channeling and dissociation through a phenomenological
      analysis. Qualitative data were obtained through interviews with 20 Israeli women
      who practice channeling. The analysis revealed 3 themes: dissociation,
      absorption, and control. The channelers' descriptions correspond with what is
      coined as "dissociative states" and enable an emic view of the etic definition of
      dissociation. 

PMID- 25978087
TI  - Creating past-life identity in hypnotic regression.
AB  - To examine the role of hypnotic suggestion in identity in past-life regression, 2
      experiments were conducted at the request of Korea's major national television
      companies. A real historical person and a fictional character were selected as
      past-life identities. After hypnotic induction, a past-life regression suggestion
      was given. While counting backward to past-life, the suggestion of a specific
      identity was interspersed 3 times. In 5 of 6 subjects, the same past-life
      identity that had been suggested was produced, with relatively rich content
      accompanied by emotional and historical facts identical to the suggested
      identity. This study found that it was quite simple and easy to manipulate past
      life identity. The role of suggestion in the formation of past-life memories
      during hypnosis is crucial. 

PMID- 25978088
TI  - Crystal Structures of Polymorphic Prion Protein beta1 Peptides Reveal Variable
      Steric Zipper Conformations.
AB  - The pathogenesis of prion diseases is associated with the conformational
      conversion of normal, predominantly alpha-helical prion protein (PrP(C)) into a
      pathogenic form that is enriched with beta-sheets (PrP(Sc)). Several PrP(C)
      crystal structures have revealed beta1-mediated intermolecular sheets, suggesting
      that the beta1 strand may contribute to a possible initiation site for beta-sheet
      mediated PrP(Sc) propagation. This beta1 strand contains the polymorphic residue
      129 that influences disease susceptibility and phenotype. To investigate the
      effect of the residue 129 polymorphism on the conformation of amyloid-like
      continuous beta-sheets formed by beta1, crystal structures of beta1 peptides
      containing each of the polymorphic residues were determined. To probe the
      conformational influence of the peptide construct design, four different lengths
      of beta1 peptides were studied. From the 12 peptides studied, 11 yielded crystal
      structures ranging in resolution from 0.9 to 1.4 A. This ensemble of beta1
      crystal structures reveals conformational differences that are influenced by both
      the nature of the polymorphic residue and the extent of the peptide construct,
      indicating that comprehensive studies in which peptide constructs vary are a more
      rigorous approach to surveying conformational possibilities. 

PMID- 25978089
TI  - Formation Process of Eosin Y-Adsorbing ZnO Particles by Electroless Deposition
      and Their Photoelectric Conversion Properties.
AB  - The thin films consisting of crystalline ZnO particles were prepared on fluorine
      doped tin oxide electrodes by electroless deposition. The particles were
      deposited from an aqueous solution containing zinc nitrate, dimethyamine-borane,
      and eosin Y at 328 K. As the Pd particles were adsorbed on the substrate, not
      only the eosin Y monomer but also the dimer and debrominated species were rapidly
      adsorbed on the spherical ZnO particles, which were aggregated and formed
      secondary particles. On the other hand, in the absence of the Pd particles, the
      monomer was adsorbed on the flake-shaped ZnO particles, which vertically grew on
      the substrate surface and had a high crystallinity. The photoelectric conversion
      efficiency was higher for the ZnO electrodes containing a higher amount of the
      monomer during light irradiation. 

PMID- 25978090
TI  - Flexible Boron-Doped Laser-Induced Graphene Microsupercapacitors.
AB  - Heteroatom-doped graphene materials have been intensely studied as active
      electrodes in energy storage devices. Here, we demonstrate that boron-doped
      porous graphene can be prepared in ambient air using a facile laser induction
      process from boric acid containing polyimide sheets. At the same time, active
      electrodes can be patterned for flexible microsupercapacitors. As a result of
      boron doping, the highest areal capacitance of as-prepared devices reaches 16.5
      mF/cm(2), 3 times higher than nondoped devices, with concomitant energy density
      increases of 5-10 times at various power densities. The superb cyclability and
      mechanical flexibility of the device are well-maintained, showing great potential
      for future microelectronics made from this boron-doped laser-induced graphene
      material. 

PMID- 25978091
TI  - Redox-neutral palladium-catalyzed C-H functionalization to form isoindolinones
      with carboxylic acids or anhydrides as readily available starting materials.
AB  - An operationally simple, Pd-catalyzed C-H functionalization is described for the
      synthesis of important and useful isoindolinones from readily available
      carboxamides and carboxylic acids or anhydrides. The reactions proceed
      efficiently with a broad range of substrates under redox-neutral reaction
      conditions and tolerate a diversity of functional groups. The mechanistic
      investigation suggests that the reactions involve C-H activation, nucleophilic
      addition, beta-O elimination, and dehydration steps. 

PMID- 25978092
TI  - DBDiaSNP: An Open-Source Knowledgebase of Genetic Polymorphisms and Resistance
      Genes Related to Diarrheal Pathogens.
AB  - Diarrhea is a highly common infection among children, responsible for significant
      morbidity and mortality rate worldwide. After pneumonia, diarrhea remains the
      second leading cause of neonatal deaths. Numerous viral, bacterial, and parasitic
      enteric pathogens are associated with diarrhea. With increasing antibiotic
      resistance among enteric pathogens, there is an urgent need for global
      surveillance of the mutations and resistance genes primarily responsible for
      resistance to antibiotic treatment. Single Nucleotide Polymorphisms are important
      in this regard as they have a vast potential to be utilized as molecular
      diagnostics for gene-disease or pharmacogenomics association studies linking
      genotype to phenotype. DBDiaSNP is a comprehensive repository of mutations and
      resistance genes among various diarrheal pathogens and hosts to advance
      breakthroughs that will find applications from development of sequence-based
      diagnostic tools to drug discovery. It contains information about 946 mutations
      and 326 resistance genes compiled from literature and various web resources. As
      of March 2015, it houses various pathogen genes and the mutations responsible for
      antibiotic resistance. The pathogens include, for example, DEC (Diarrheagenic
      E.coli), Salmonella spp., Campylobacter spp., Shigella spp., Clostridium
      difficile, Aeromonas spp., Helicobacter pylori, Entamoeba histolytica, Vibrio
      cholera, and viruses. It also includes mutations from hosts (e.g., humans, pigs,
      others) that render them either susceptible or resistant to a certain type of
      diarrhea. DBDiaSNP is therefore intended as an integrated open access database
      for researchers and clinicians working on diarrheal diseases. Additionally, we
      note that the DBDiaSNP is one of the first antibiotic resistance databases for
      the diarrheal pathogens covering mutations and resistance genes that have
      clinical relevance from a broad range of pathogens and hosts. For future
      translational research involving integrative biology and global health, the
      database offers veritable potentials, particularly for developing countries and
      worldwide monitoring and personalized effective treatment of pathogens associated
      with diarrhea. The database is accessible on the public domain at
      http://www.juit.ac.in/attachments/dbdiasnp/ . 

PMID- 25978094
TI  - Ipso-Borylation of Aryl Ethers via Ni-Catalyzed C-OMe Cleavage.
AB  - A Ni-catalyzed ipso-borylation of aryl ethers via C(sp(2))-OMe and C(sp(3))-OMe
      cleavage is described. The transformation is characterized by its wide substrate
      scope under mild conditions and an exquisite divergence in site selectivity that
      can be easily switched by selecting the appropriate boron reagent. 

PMID- 25978093
TI  - Combining Step Gradients and Linear Gradients in Density.
AB  - Combining aqueous multiphase systems (AMPS) and magnetic levitation (MagLev)
      provides a method to produce hybrid gradients in apparent density. AMPS-solutions
      of different polymers, salts, or surfactants that spontaneously separate into
      immiscible but predominantly aqueous phases-offer thermodynamically stable steps
      in density that can be tuned by the concentration of solutes. MagLev-the
      levitation of diamagnetic objects in a paramagnetic fluid within a magnetic field
      gradient-can be arranged to provide a near-linear gradient in effective density
      where the height of a levitating object above the surface of the magnet
      corresponds to its density; the strength of the gradient in effective density can
      be tuned by the choice of paramagnetic salt and its concentrations and by the
      strength and gradient in the magnetic field. Including paramagnetic salts (e.g.,
      MnSO4 or MnCl2) in AMPS, and placing them in a magnetic field gradient, enables
      their use as media for MagLev. The potential to create large steps in density
      with AMPS allows separations of objects across a range of densities. The
      gradients produced by MagLev provide resolution over a continuous range of
      densities. By combining these approaches, mixtures of objects with large
      differences in density can be separated and analyzed simultaneously. Using MagLev
      to add an effective gradient in density also enables tuning the range of
      densities captured at an interface of an AMPS by simply changing the position of
      the container in the magnetic field. Further, by creating AMPS in which phases
      have different concentrations of paramagnetic ions, the phases can provide
      different resolutions in density. These results suggest that combining steps in
      density with gradients in density can enable new classes of separations based on
      density.

PMID- 25978095
TI  - Prevalence, awareness, treatment and control of hypertension in Tibetan monks
      from Gansu Province, Northwest China.
AB  - Tibetan monks are a special group in life style and diet customs. We have little
      information of hypertension about them. Therefore, the objective of this study
      was to investigate the information on the prevalence, awareness, treatment and
      control of hypertension in these populations. A cross-sectional study of
      hypertension was carried out in 984 monks and 1042 Tibetan residents' controls in
      the same area. All the subjects were selected for interview, and physical
      examination involved blood pressure (BP) measurement. The overall prevalence of
      hypertension in monks was significantly lower than those in local residents
      (19.3% versus 34.1%; p < 0.01). The rates of awareness, treatment and control in
      monks were also lower than those in local residents (9.5% versus 16.9%, 4.2%
      versus 13.2% and 1.6% versus 4.5%; p < 0.01 for each). These findings indicated
      that a low prevalence of hypertension among monks aged 18 years and over in
      Gannan Tibetan autonomous district of Gansu province in China. We concluded that
      the relatively healthy diet and ways of life in monks were the major contributing
      factors to the lower prevalence of hypertension. However, the awareness,
      treatment and control rates of hypertension were also low. The possible reasons
      were most likely due to the difficult access to quality medical care and poor
      health education. 

PMID- 25978096
TI  - Hypoglycemia Reduction and Accuracy of Continuous Glucose Monitoring.

PMID- 25978097
TI  - A novel antimicrobial flavonoid from the stem bark of Commiphora pedunculata
      (Kotschy & Peyr.) Engl.
AB  - A new flavonoid, 2-(3,5-dihydroxy-4-methoxy-phenyl)-3,5-dihydroxy-8,8-dimethyl
      2,3-dihydro-8H-pyrano[3,2]chromen-4-one, together with previously reported
      epicatechin was isolated from the ethyl acetate soluble fraction of the methanol
      extract of the stem bark of Commiphora pedunculata. The structures of these
      compounds were elucidated based on extensive analysis of their spectral data,
      including 1 and 2D NMR. The compounds were active against 9 out of 12 tested
      microorganisms including a resistant strain; vancomycin-resistant entrococci
      (VRE), Escherichia coli, Staphylococcus aureus and Candida albicans. The zones of
      inhibition ranged between 22 and 34 mm against the microorganisms. The minimum
      inhibitory concentration was as low as 6.25 MUg/mL against Shigella dysentriae,
      Bacillus cereus and S. aureus while the minimum bactericidal concentration was as
      low as 50 MUg/mL against Pseudomonas aeruginosa, VRE and C. albicans. This is the
      first report of the isolation of the compound. 

PMID- 25978098
TI  - Two new triterpenoid saponins from Ilex cornuta.
AB  - Two new triterpenoid saponins (1 and 2) were isolated from the stems of Ilex
      cornuta, along with two known triterpenoids (3 and 4). The structures of
      compounds 1 and 2 were determined as ursane-12,19-diene-28-oic acid 3beta-O-beta
      D-glucuronopyranoside-6-O-methyl ester (1), 3alpha,23alpha-dihydroxy-olean
      9(11),12-diene-28-oic acid 28-O-beta-D-glucopyranosyl ester (2), on the basis of
      hydrolysis and spectral evidence, including 1D and 2D NMR and high resolution
      electrospray ionization mass spectrometry (HR-ESI-MS) analyses. Protective
      effects of compounds 1-4 were tested against H(2)O(2)-induced H9c2 cardiomyocyte
      injury, and the data showed that all these compounds had no cell-protective
      effect.

PMID- 25978099
TI  - Proximal Rectus Femoris Avulsion: Ultrasonic Diagnosis and Nonoperative
      Management.
AB  - OBJECTIVE: To present a case of ultrasonic diagnosis and nonoperative management
      of a complete proximal rectus femoris avulsion in a National Collegiate Athletic
      Association Division 1 soccer goalkeeper. BACKGROUND: While delivering a goal
      kick, a previously uninjured 24-year-old collegiate soccer goalkeeper had the
      sudden onset of right anterior thigh pain. He underwent rehabilitation with rapid
      resolution of his presenting pain but frequent intermittent recurrence of
      anterior thigh pain. After he was provided a definitive diagnosis with
      musculoskeletal ultrasound, he underwent an extended period of rehabilitation and
      eventually experienced complete recovery without recurrence. DIFFERENTIAL
      DIAGNOSIS: Rectus femoris avulsion, rectus femoris strain or partial tear,
      inguinal hernia, or acetabular labral tear. TREATMENT: Operative and nonoperative
      options were discussed. In view of the player's recovery, nonoperative options
      were pursued with a good result. UNIQUENESS: Complete proximal rectus femoris
      avulsions are rare. Our case contributes to the debate on whether elite-level
      kicking and running athletes can return to full on-field performance without
      surgery. CONCLUSIONS: Complete proximal rectus femoris avulsions can be treated
      effectively using nonoperative measures with good preservation of function even
      in the elite-level athlete. In addition, musculoskeletal ultrasound is an
      excellent tool for on-site evaluation and may help guide prognosis and
      management.

PMID- 25978100
TI  - Days to Return to Participation After a Hamstrings Strain Among American
      Collegiate Soccer Players.
AB  - CONTEXT: Among US collegiate soccer players, the incidence rate and the event
      characteristics of hamstrings strains differ between sexes, but comparisons in
      the return-to-participation (RTP) time have not been reported. OBJECTIVE: To
      compare the RTP time between male and female collegiate soccer players and
      analyze the influence of event characteristics on the RTP time for each sex.
      DESIGN: Descriptive epidemiology study. SETTING: Data were collected from
      collegiate teams that voluntarily participated in the National Collegiate
      Athletic Association Injury Surveillance System. PATIENTS OR OTHER PARTICIPANTS:
      Collegiate soccer athletes who sustained 507 hamstrings strains (306 men, 201
      women) during the 2004 through 2009 fall seasons. MAIN OUTCOME MEASURE(S):
      Nonparametric statistics were used to evaluate RTP time differences between sexes
      and among categories of each event characteristic (ie, time of season, practice
      or competition, player position). Negative binomial regression was used to model
      the RTP time for each sex. All analyses were performed separately for first-time
      and recurrent strains. RESULTS: We found no differences in the RTP time between
      sexes for first-time (median: men = 7.0 days, women = 6.0 days; P = .07) or
      recurrent (median: men = 11 days, women = 5.5 days; P = .06) hamstrings strains.
      For male players with first-time strains, RTP time was increased when the strain
      occurred during competition or the in-season/postseason and varied depending on
      the division of play. Among female players with first-time strains, we found no
      differences in RTP time within characteristics. For male players with recurrent
      hamstrings strains, the RTP time was longer when the injury occurred during the
      in-season/postseason. Among female players with recurrent strains, RTP time was
      longer for forwards than for midfielders or defenders. CONCLUSIONS: Although we
      found no differences in the RTP time after hamstrings strains in male and female
      collegiate soccer players, each sex had unique event characteristics that
      influenced RTP time.

PMID- 25978101
TI  - Drop-Landing Performance and Knee-Extension Strength After Anterior Cruciate
      Ligament Reconstruction.
AB  - CONTEXT: Individuals with a history of anterior cruciate ligament reconstruction
      (ACLR) are at greater risk of reinjury and developing early-onset osteoarthritis
      due to persistent abnormal joint loading. Real-time clinical assessment tools may
      help identify patients experiencing abnormal movement patterns after ACLR.
      OBJECTIVE: To compare performance on the Landing Error Scoring System (LESS)
      between participants with ACLR and uninjured control participants and to
      determine the relationship between LESS score and knee-extension strength in
      these participants. DESIGN: Controlled laboratory study. SETTING: Research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty-six recreationally active
      participants, consisting of 22 with ACLR (12 men, 10 women; age = 22.5 +/- 5.0
      years, height = 172.8 +/- 7.2 cm, mass = 74.2 +/- 15.6 kg, body mass index = 24.6
      +/- 4.0) and 24 healthy control participants (12 men, 12 women; age = 21.7 +/-
      3.6 years, height = 168.0 +/- 8.8 cm, mass = 69.2 +/- 13.6 kg, body mass index =
      24.3 +/- 3.2) were enrolled. MAIN OUTCOME MEASURE(S): Bilateral normalized knee
      extension maximal voluntary isometric contraction (MVIC) torque (Nm/kg) and LESS
      scores were measured during a single testing session. We compared LESS scores
      between groups using a Mann-Whitney U test and the relationships between LESS
      scores and normalized knee-extension MVIC torque using Spearman rho bivariate
      correlations. RESULTS: The ACLR participants had a greater number of LESS errors
      (6.0 +/- 3.6) than healthy control participants (2.8 +/- 2.2; t44 = -3.73, P =
      .002). In ACLR participants, lower normalized knee-extension MVIC torque in the
      injured limb (rho = -0.455, P = .03) was associated with a greater number of
      landing errors. CONCLUSIONS: Participants with ACLR displayed more errors while
      landing. The occurrence of landing errors was negatively correlated with knee
      extension strength, suggesting that weaker participants had more landing errors.
      Persistent quadriceps weakness commonly associated with ACLR may be related to a
      reduced quality of lower extremity movement during dynamic tasks.

PMID- 25978102
TI  - Mesenteric Defect with Internal Herniation: A Rare Cause of Bowel Obstruction in
      Newborn.
AB  - Herniation through a congenital mesenteric defect is a rare cause of intestinal
      obstruction in the newborn. Early diagnosis and surgical treatment improves the
      prognosis. We present a case of a full-term infant who presented with respiratory
      distress at birth. Enteral feeding was not started because abdominal distension
      and delayed passage of meconium. Bowel obstruction was suspected. Radiological
      investigation did not provide a clear diagnosis. Surgical exploration revealed
      transmesenteric congenital hernia. After surgical repair, enteral feeding was
      tolerated and patient was discharged with an uneventful outcome. Diagnostic
      difficulties were discussed. 

PMID- 25978104
TI  - Deciphering the Positional Influence of the Hydroxyl Group in the Cinnamoyl Part
      of 3-Hydroxy Flavonoids for Structural Modification and Their Interaction with
      the Protonated and B Form of Calf Thymus DNA Using Spectroscopic and Molecular
      Modeling Studies.
AB  - Studies on the interaction of naturally occurring flavonoids with different
      polymorphic forms of nucleic acid are helpful for understanding the molecular
      aspects of binding mode and providing direction for the use and design of new
      efficient therapeutic agents. However, much less information is available on the
      interactions of these compounds with different polymorphic forms of DNA at the
      molecular level. In this report we investigated the interaction of two widely
      abundant dietary flavonoids quercetin (Q) and morin (M) with calf thymus (CT)
      DNA. Spectrophotometric, spectropolarimetric, viscosity measurement, and
      molecular docking simulation methods are used as tools to delineate the binding
      mode and probable location of the flavonoids and their effects on the stability
      and conformation of DNA. It is observed that in the presence of the protonated
      form of DNA the dual fluorescence of Q and M resulting from the excited-state
      intramolecular proton transfer (ESIPT) is modified significantly. Structural
      analysis showed Q and M binds weakly to the B form (groove binding) compared to
      the protonated form of CT DNA (electrostatic interaction). In both cases, Q binds
      strongly to both forms of DNA compared to M. 

PMID- 25978103
TI  - A Workflow to Investigate Exposure and Pharmacokinetic Influences on High
      Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways.
AB  - BACKGROUND: Adverse outcome pathways (AOPs) link adverse effects in individuals
      or populations to a molecular initiating event (MIE) that can be quantified using
      in vitro methods. Practical application of AOPs in chemical-specific risk
      assessment requires incorporation of knowledge on exposure, along with
      absorption, distribution, metabolism, and excretion (ADME) properties of
      chemicals. OBJECTIVES: We developed a conceptual workflow to examine exposure and
      ADME properties in relation to an MIE. The utility of this workflow was evaluated
      using a previously established AOP, acetylcholinesterase (AChE) inhibition.
      METHODS: Thirty chemicals found to inhibit human AChE in the ToxCastTM assay were
      examined with respect to their exposure, absorption potential, and ability to
      cross the blood-brain barrier (BBB). Structures of active chemicals were compared
      against structures of 1,029 inactive chemicals to detect possible parent
      compounds that might have active metabolites. RESULTS: Application of the
      workflow screened 10 "low-priority" chemicals of 30 active chemicals. Fifty-two
      of the 1,029 inactive chemicals exhibited a similarity threshold of >= 75% with
      their nearest active neighbors. Of these 52 compounds, 30 were excluded due to
      poor absorption or distribution. The remaining 22 compounds may inhibit AChE in
      vivo either directly or as a result of metabolic activation. CONCLUSIONS: The
      incorporation of exposure and ADME properties into the conceptual workflow
      eliminated 10 "low-priority" chemicals that may otherwise have undergone
      additional, resource-consuming analyses. Our workflow also increased confidence
      in interpretation of in vitro results by identifying possible "false negatives."
      CITATION: Phillips MB, Leonard JA, Grulke CM, Chang DT, Edwards SW, Brooks R,
      Goldsmith MR, El-Masri H, Tan YM. 2016. A workflow to investigate exposure and
      pharmacokinetic influences on high-throughput in vitro chemical screening based
      on adverse outcome pathways. Environ Health Perspect 124:53-60;
      http://dx.doi.org/10.1289/ehp.1409450.

PMID- 25978105
TI  - In vitro synergy of colistin combinations against extensively drug-resistant
      Acinetobacter baumannii producing OXA-23 carbapenemase.
AB  - Fifty extensively drug-resistant Acinetobacter baumannii (XDRAB) were isolated
      from patients. The chequerboard microdilution method was used to determine the in
      vitro activities of five colistin (COL)-based combinations including
      COL+fosfomycin (FOS), COL+rifampicin (RIF), COL+imipenem (IMP), COL+sulbactam
      (SUP) and COL+levofloxacin (LVX). The synergistic activity was evaluated by the
      fractional inhibitory concentration index (FICI). According to our results, the
      combination of COL was synergistic with FOS, RIF, IMP, SUP and LVX with the
      ratios of 50, 72, 88, 92 and 64%, respectively. When combined with COL, the other
      five agents showed increased antimicrobial activities. In addition, two of the
      combinations, COL+RIF and COL+IMP, were more active than the combinations of
      COL+FOS, COL+SUP and COL+LVX. More importantly, these combination regimens could
      exert synergistic effects at the sub-minimum inhibitory concentration (MIC)
      levels against XDRAB strains. 

PMID- 25978106
TI  - The Use of 123I in Diagnostic Radioactive Iodine Scans in Children with
      Differentiated Thyroid Carcinoma.
AB  - BACKGROUND: Adult studies have shown that iodine-123 ((123)I) is as effective as
      (131)I in detecting metastatic disease in patients with differentiated thyroid
      carcinoma. However, the type and administered activity of radioiodine used for
      diagnostic imaging of metastatic thyroid cancer has not been well studied in
      children. Here we describe our institution's experience with using (123)I in
      diagnostic radioiodine scans in children with differentiated thyroid carcinoma.
      METHODS: Every patient with differentiated thyroid carcinoma who completed
      diagnostic scanning followed by radioiodine therapy at our institution over the
      past 8 years was included in this retrospective chart review. Patient age, sex,
      presentation of thyroid disease, past medical history, thyrotropin,
      thyroglobulin, and antithyroglobulin antibodies were recorded. A single nuclear
      medicine radiologist evaluated all scans. RESULTS: Thirty-three subjects
      completed 37 pairs of scans at a mean age of 13.4 years (range 6-17 years). The
      majority of subjects were female (81%) and had papillary thyroid cancer (91%).
      For diagnostic scanning, 5 received 2 mCi of (131)I, 21 received 2 mCi of (123)I,
      and 11 received 3 mCi of (123)I. There was no statistically significant
      difference in rate of discordant scan pairs when comparing (131)I and (123)I (20%
      and 23% respectively, p=0.9). The detection of metastatic pulmonary disease on
      diagnostic scanning was not improved by increasing the dose of (123)I from 2 mCi
      to 3 mCi (10% rate of missed lung detection with 2 mCi (123)I vs. 20% with 3 mCi
      (123)I). CONCLUSIONS: (123)I is effective for use in diagnostic radioactive
      iodine scans in children with differentiated thyroid cancer. The primary
      advantages of using (123)I include decreased radiation exposure and avoidance of
      stunning. However, in children there is a possibility of missed detection of
      metastatic pulmonary disease.

PMID- 25978108
TI  - Synthetic Glucocorticoids and Early Variations of Blood Pressure: A Population
      Based Cohort Study.
AB  - CONTEXT: Endogenous glucocorticoids are known to increase blood pressure, but
      very little is known about the early effects of synthetic glucocorticoids (eg,
      prednisone, dexamethasone) on blood pressure. OBJECTIVE: To assess longitudinal
      variations of blood pressure before and after initiation of systemic
      glucocorticoid therapy. DESIGN, SETTING, AND PATIENTS: Adult patients prescribed
      synthetic glucocorticoid therapy for at least 3 months and registered between
      2004 and 2012 in The Health Improvement Network (THIN) primary care database.
      MAIN OUTCOME MEASURE: Systolic and diastolic blood pressure as measured in
      primary care. RESULTS: Among the 16,351 patients prescribed antihypertensive drug
      within the year before glucocorticoid initiation (women, 57.1%; age [mean +/-
      SD], 72.0 +/- 11.4 y), the mean (SD) blood pressure within the year before
      glucocorticoid initiation was 140 (18)/78 (9) mm Hg. It was 139 (19)/77 (11), 139
      (19)/77 (10), and 139 (19)/77 (11) mm Hg during the first, second, and third
      months of exposure, respectively. We did not find any evidence of the effects of
      glucocorticoids on blood pressure in these patients. Among the 6914 patients not
      prescribed antihypertensive drug within the year before glucocorticoid initiation
      (women, 64.9%; age, 60.0 +/- 17.8 y), the figures were 133 (17)/78 (10), 135
      (20)/79 (11), 133 (19)/78 (11), and 133 (19)/78 (11) mm Hg before exposure and
      during the first, second, and third months of exposure, respectively. In this
      group of patients, glucocorticoid exposure was associated with a slight (<1 mm
      Hg; P = .03) increase of systolic but not diastolic (P = .52) blood pressure.
      However, in 4% of people or fewer, extreme increases or decreases (ie, >=30 mm Hg
      for systolic blood pressure) in blood pressure were observed after glucocorticoid
      initiation. Prednisone/prednisolone use was associated with a higher risk of
      extreme increase in systolic blood pressure than the other synthetic
      glucocorticoids (odds ratio, 4.9 [95% confidence interval, 1.9-12.6]; P = .001).
      CONCLUSION: Contrary to what is usually thought, the increase of blood pressure
      during the first months of exposure to synthetic glucocorticoids seems clinically
      nonsignificant.

PMID- 25978107
TI  - Loss-of-Function Variants in a Hungarian Cohort Reveal Structural Insights on TSH
      Receptor Maturation and Signaling.
AB  - CONTEXT: Congenital hypothyroidism (CH) is one of the most common inborn
      endocrine disorders with genetic background. Despite the well-established newborn
      CH screening program in Hungary, no systematic examination of the underlying
      genetic alterations has been performed as yet. OBJECTIVE: We aimed to explore TSH
      receptor (TSHR) mutations in a cohort of Hungarian patients with CH. PATIENTS:
      Eighty-five unrelated patients with permanent primary CH, all diagnosed at
      newborn screening, were selected. MAIN OUTCOME MEASURES: Coding exons of the TSHR
      gene were sequenced and evaluated together with the thyroid-specific clinical
      parameters. Functional features of the novel mutations were experimentally
      examined, and their comparative molecular models were built. RESULTS: In four
      patients (one heterozygous and three compound heterozygous), seven TSHR mutations
      were identified. Among these, N432(1.50)D and P449(2.39)L are novel missense
      alterations. Importantly, the N432(1.50) residue is highly conserved among G
      protein-coupled receptors, and its function has not been examined yet in human
      glycoprotein hormone receptors. Our results indicate that the N432(1.50)D
      mutation disrupts important, architecture-stabilizing intramolecular interactions
      and ultimately leads to the complete intracellular retention of the receptor. On
      the other hand, P449(2.39) is located in the intracellular part of the receptor,
      which is important in G protein coupling. The P449(2.39)L mutation results in
      signaling impairment, with a more profound effect on the Gq/11 pathway.
      CONCLUSION: TSHR mutations are common among Hungarian patients with CH. The novel
      genetic alterations revealed an important structural role of the N432(1.50) and
      the P449(2.39) residues in receptor expression and signaling, respectively.

PMID- 25978109
TI  - Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo
      and Improves High-Density Lipoprotein Function in Patients With
      Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial.
AB  - CONTEXT: We have found that hydrogen (dihydrogen [H2]) decreases plasma low
      density lipoprotein (LDL) cholesterol levels and improves high-density
      lipoprotein (HDL) function in patients with potential metabolic syndrome in a
      before-after self-controlled study. OBJECTIVE: The purpose of this study was to
      further characterize the effects of H2-rich water (0.9 L/day) on the content,
      composition, and biological activities of plasma lipoproteins on patients with
      hypercholesterolemia and their underlying mechanisms in a double-blinded,
      randomized, and placebo-controlled trial. DESIGN: This was a case-control study.
      SETTING: The setting was the Zhoudian community, Tai'an, China. PATIENTS: A total
      of 68 patients with untreated isolated hypercholesterolemia were randomly
      allocated to either drinking H2-rich water (n = 34) or placebo water (n = 34) for
      10 weeks. RESULTS: HDL isolated from the H2 group showed an increased ability to
      promote the ATP-binding cassette transporter A1-mediated cholesterol efflux ex
      vivo. Plasma pre-beta-HDL levels were up-regulated although there were no changes
      in plasma HDL-cholesterol levels. Moreover, other HDL functions, assessed in
      protection against LDL oxidation, inhibition of oxidized-LDL-induced
      inflammation, and protection of endothelial cells from oxidized-LDL-induced
      apoptosis, were all significantly improved by H2 treatment. In addition, H2
      treatment increased the effective rate in down-regulating plasma levels of total
      cholesterol (47.06% vs 17.65%) and LDL cholesterol (47.06% vs 23.53%). Western
      blot analysis revealed a marked decrease in apolipoprotein B100 and an increase
      in apolipoprotein M in plasma of the H2 group. Finally H2 treatment resulted in a
      significant reduction in the levels of several inflammatory and oxidative stress
      indicators in whole plasma and HDL particles. CONCLUSIONS: H2 activates ATP
      binding cassette transporter A1-dependent efflux, enhances HDL
      antiatherosclerotic functions, and has beneficial lipid-lowering effects. The
      present findings highlight the potential role of H2 in the regression of
      hypercholesterolemia and atherosclerosis.

PMID- 25978110
TI  - Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With
      Hypogonadotropic Hypogonadodism.
AB  - CONTEXT: We investigated the efficacy and safety of two different treatments that
      have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism
      (HH). OBJECTIVE: The objective of the study was to assess the effectiveness and
      safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys
      with HH. DESIGN: Twelve patients received 8-10 MUg of GnRH, sc injected every 90
      minutes using a pump. Another 22 patients received hCG, injected im as follows:
      for the first 3 months, 1000 IU of hCG was injected two times per week and then
      once every other day for the next 3 months. The dose of hCG was increased to 2000
      IU after a 6-month treatment and the above cycle was repeated for another 6
      months. All patients were treated for 12-14 months and followed up every 3
      months. SETTING: Thirty-five participants were chosen from Beijing Children's
      Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12
      with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10
      to 16 years. INTERVENTION(S): Twelve patients were treated with pulsatile pump
      GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient
      was treated successively with hCG and GnRH, which was removed in data analysis.
      MAIN OUTCOME MEASURE(S): Testicular volume was measured by an orchidometer. The
      levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay.
      Bone age was measured by x-ray. RESULTS: Patients treated with GnRH showed larger
      testes than those treated with hCG. Patients in both groups showed a
      significantly increased length of penis and T levels. But the difference of the
      two groups was not statistically significant. There was no significant difference
      in side effects in both groups. CONCLUSIONS: Boys with HH may be effectively
      treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating
      adolescent boys with HH than hCG.

PMID- 25978112
TI  - Temperature and Pressure-Dependent Rate Coefficients for the Reaction of Vinyl
      Radical with Molecular Oxygen.
AB  - State-of-the-art calculations of the C2H3O2 potential energy surface are
      presented. A new method is described for computing the interaction potential for
      R + O2 reactions. The method, which combines accurate determination of the
      quartet potential along the doublet minimum energy path with multireference
      calculations of the doublet/quartet splitting, decreases the uncertainty in the
      doublet potential and thence the rate constants by more than a factor of 2. The
      temperature- and pressure-dependent rate coefficients are computed using variable
      reaction coordinate transition-state theory, variational transition-state theory,
      and conventional transition-state theory, as implemented in a new RRKM/ME code.
      The main bimolecular product channels are CH2O + HCO at lower temperatures and
      CH2CHO + O at higher temperatures. Above 10 atm, the collisional stabilization of
      CH2CHOO directly competes with these two product channels. CH2CHOO decomposes
      primarily to CH2O + HCO. The next two most significant bimolecular products are
      OCHCHO + H and (3)CHCHO + OH, and not C2H2 + HO2. C2H3 + O2 will be predominantly
      chain branching above 1700 K. Uncertainty analysis is presented for the two most
      important transition states. The uncertainties in these two barrier heights
      result in a significant uncertainty in the temperature at which CH2CHO + O
      overtakes all other product channels. 

PMID- 25978111
TI  - AMH as Predictor of Premature Ovarian Insufficiency: A Longitudinal Study of 120
      Turner Syndrome Patients.
AB  - CONTEXT: The majority of Turner syndrome (TS) patients suffer from accelerated
      loss of primordial follicles. Low circulating levels of anti-Mullerian hormone
      (AMH) may predict the lack of spontaneous puberty in prepubertal girls and
      imminent premature ovarian insufficiency (POI) in TS women with preserved ovarian
      function. OBJECTIVES: To evaluate the association between circulating AMH and
      ovarian status in TS patients. DESIGN: Longitudinal observational cohort study.
      SETTING: Tertiary referral center for pediatric and gynecologic endocrinology.
      PARTICIPANTS: A total of 120 TS patients, aged 0 to 48 years. MAIN OUTCOME
      MEASURES: Longitudinal measurements of AMH, FSH, LH, estradiol, and inhibin B
      according to age, karyotype (45,X; 45,X/46,XX mosaicism; miscellaneous
      karyotypes), and ovarian status (group 0, prepubertal; group 1, never ovarian
      function; group 2, ongoing ovarian function; and group 3, loss of ovarian
      function). RESULTS: Ovarian status was highly associated with the TS karyotype:
      spontaneous puberty-45,X (three of 44 patients), 45,X/46,XX (15 of 17),
      miscellaneous (17 of 42); and POI-45,X (three of three), 45,X/46,XX (one of 15),
      and miscellaneous (eight of 17). AMH was associated with ovarian status (eg,
      group 1, <2 pmol/L; vs group 2, 19 pmol/L; P < .001). AMH < 4 pmol/L
      (corresponding to <-2 SD) predicted absent puberty in prepubertal girls and POI
      in adolescent and adult patients. CONCLUSION: The majority of women with mosaic
      karyotype 45,X/46,XX had ongoing ovarian function in early adulthood. AMH < -2 SD
      predicted failure to enter puberty in young TS girls and imminent POI in
      adolescent and adult TS patients.

PMID- 25978113
TI  - Holistic Needs of University Students with Invisible Disabilities: A Qualitative
      Study.
AB  - AIM: To inform rehabilitation professionals' role in supporting transition to
      higher education through identification and description of disability related
      needs experienced by university students. METHODS: Participants were recruited
      from a large research-intensive university in the southeastern United States and
      included 13 students eligible for university disability services, 9 university
      personnel, and 1 parent of a university student with a disability. Disabilities
      of study participants were invisible; all but one chose to disclose diagnostic
      information. Data from 15 individual interviews and 2 focus groups were analyzed
      for themes. RESULTS: The Navigating Parallel Demands theme elucidates the ways
      disability related needs extended beyond the classroom to areas of health and
      wellness, social, and daily living. Navigation in Context describes personal and
      environmental circumstances surrounding processes used to meet a broad-range of
      demands. CONCLUSION: University participation requires students with disabilities
      to navigate and manage a wide range of demands while securing appropriate
      supports. Findings inform rehabilitation professionals in providing anticipatory
      guidance when preparing students with invisible disabilities for postsecondary
      educational transitions.

PMID- 25978114
TI  - Validation of an in vitro 3D bone culture model with perfused and mechanically
      stressed ceramic scaffold.
AB  - An engineered three dimensional (3D) in vitro cell culture system was designed
      with the goal of inducing and controlling in vitro osteogenesis in a reproducible
      manner under conditions more similar to the in vivo bone microenvironment than
      traditional two-dimensional (2D) models. This bioreactor allows efficient
      mechanical loading and perfusion of an original cubic calcium phosphate
      bioceramic of highly controlled composition and structure. This bioceramic
      comprises an internal portion containing homogeneously interconnected macropores
      surrounded by a dense layer, which minimises fluid flow bypass around the
      scaffold. This dense and flat layer permits the application of a homogeneous
      loading on the bioceramic while also enhancing its mechanical strength. Numerical
      modelling of constraints shows that the system provides direct mechanical
      stimulation of cells within the scaffold. Experimental results establish that
      under perfusion at a steady flow of 2 uL/min, corresponding to 3 <= Medium
      velocity <= 23 um/s, mouse calvarial cells grow and differentiate as osteoblasts
      in a reproducible manner, and lay down a mineralised matrix. Moreover, cells
      respond to mechanical loading by increasing C-fos expression, which demonstrates
      the effective mechanical stimulation of the culture within the scaffold. In
      summary, we provide a "proof-of-concept" for osteoblastic cell culture in a
      controlled 3D culture system under perfusion and mechanical loading. This model
      will be a tool to analyse bone cell functions in vivo, and will provide a bench
      testing system for the clinical assessment of bioactive bone-targeting molecules
      under load.

PMID- 25978115
TI  - In vivo biological response to extracorporeal shockwave therapy in human
      tendinopathy.
AB  - Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic
      tendinopathies, however little is known about the in-vivo biological mechanisms
      of ESWT. Using microdialysis, we examined the real-time biological response of
      healthy and pathological tendons to ESWT. A single session of ESWT was
      administered to the mid-portion of the Achilles tendon in thirteen healthy
      individuals (aged 25.7 +/- 7.0 years) and patellar or Achilles tendon of six
      patients with tendinopathies (aged 39.0 +/- 14.9 years). Dialysate samples from
      the surrounding peri-tendon were collected before and immediately after ESWT.
      Interleukins (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A,
      vascular endothelial growth factor and interferon-gamma were quantified using a
      cytometric bead array while gelatinase activity (MMP-2 and -9) was examined using
      zymography. There were no statistical differences between the biological tissue
      response to ESWT in healthy and pathological tendons. IL-1beta, IL-2, IL-6 and IL
      8 were the cytokines predominantly detected in the tendon dialysate. IL-1beta and
      IL-2 did not change significantly with ESWT. IL-6 and IL-8 concentrations were
      elevated immediately after ESWT and remained significantly elevated for four
      hours post-ESWT (p < 0.001). Pro-forms of MMP-2 and -9 also increased after ESWT
      (p < 0.003), whereas there were no significant changes in active MMP forms. In
      addition, the biological response to ESWT treatment could be differentiated
      between possible responders and non-responders based on a minimum 5-fold increase
      in any inflammatory marker or MMP from pre- to post-ESWT. Our findings provide
      novel evidence of the biological mechanisms underpinning ESWT in humans in vivo.
      They suggest that the mechanical stimulus provided by ESWT might aid tendon
      remodelling in tendinopathy by promoting the inflammatory and catabolic processes
      that are associated with removing damaged matrix constituents. The non-response
      of some individuals may help to explain why ESWT does not improve symptoms in all
      patients and provides a potential focus for future research.

PMID- 25978116
TI  - A new concept for implant fixation: bone-to-bone biologic fixation.
AB  - Many attempts have been made to reduce complications of bone implant, such as
      pedicle screw loosening. To address this problem, the authors suggest a new
      concept of bone-to-bone biologic fixation using recombinant human bone
      morphogenetic protein-2 (rhBMP-2)-loaded cannulated pedicle screws. Recombinant
      human bone morphogenetic protein-2 is an osteoinductive cytokine. Four types of
      titanium pedicle screws were tested (uncannulated, cannulated with no loading,
      beta-tricalcium phosphate (TCP)-loaded, and TCP/BMP2 loaded) using 16 miniature
      pigs. Radiological evaluation was conducted to assess the fusion and loosening of
      pedicle screws. Twelve weeks after implantation, peak torsional extraction torque
      was measured, and the pedicle screw and bone interface was evaluated by micro
      computed tomography (uCT) and histologic examination. The mean value of the
      radiological score was significantly greater in the TCP/BMP2 loaded group at 12
      weeks post-operation compared to those in the other groups. CT images showed
      distinct bone formation surrounding TCP/BMP2 loaded cannulated pedicle screws
      compared to the other groups. Mean extraction torsional peak torque at 12 weeks
      postoperative was more than 10-fold higher in the TCP/BMP2 loaded pedicle screw
      group than in the other groups. Bone surface and bone volume, as quantitated
      through uCT, were higher in the TCP/BMP2 loaded group. Histologic examination
      revealed bone-to-bone fixation at the interface of pedicle screws and pre
      existing bone. Bone-to-bone biologic fixation through the holes of TCP/BMP2
      loaded pedicle screws significantly increased fixation strength and represents a
      novel method that can be applied to osteoporotic or tumour spine surgeries. 

PMID- 25978117
TI  - Comparative investigation of three dose rate meters for their viability in pulsed
      radiation fields.
AB  - Pulsed radiation fields, characterized by microsecond pulse duration and
      correspondingly high pulse dose rates, are increasingly used in therapeutic,
      diagnostic and research applications. Yet, dose rate meters which are used to
      monitor radiation protection areas or to inspect radiation shielding are mostly
      designed, characterized and tested for continuous fields and show severe
      deficiencies in highly pulsed fields. Despite general awareness of the problem,
      knowledge of the specific limitations of individual instruments is very limited,
      complicating reliable measurements. We present here the results of testing three
      commercial dose rate meters, the RamION ionization chamber, the LB 1236-H
      proportional counter and the 6150AD-b scintillation counter, for their response
      in pulsed radiation fields of varied pulse dose and duration. Of these three the
      RamION proved reliable, operating in a pulsed radiation field within its
      specifications, while the other two instruments were only able to measure very
      limited pulse doses and pulse dose rates reliably. 

PMID- 25978118
TI  - Association of adipokines and inflammatory markers with lipid control in type 2
      diabetes.
AB  - INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism
      are equivocal. OBJECTIVES: The aim of this study was to evaluate the association
      of lipid control with adipokines and inflammatory markers in patients with type 2
      diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2
      diabetes. The achievement of treatment targets in terms of total cholesterol, low
      density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)
      cholesterol, and triglycerides was assessed in accordance with the current
      guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as
      well as concentrations of highmolecular-weight (HMW) adiponectin, leptin,
      resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis
      factor alpha (TNF-alpha) were measured in all patients. Logistic regression
      analyses were performed to determine the risk factors for inadequate lipid
      control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and
      triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients,
      respectively. In multivariate analyses, female sex, lower resistin
      concentrations, and the absence of statin treatment were predictors of total
      cholesterol levels above the treatment target; older age and lower statin dose-
      of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR
      index, lower HMW adiponectin concentrations, and higher TNF-alpha concentration-o
      f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW
      adiponectin concentration, and the absence of statin treatment--of triglycerides
      above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW
      adiponectin concentrations are associated with inadequate triglyceride and HDL
      control; higher TNF-alpha, with inadequate HDL control, and lower resistin
      concentrations, with inadequate total cholesterol control.

PMID- 25978121
TI  - Use of prior manufacturer specifications with Bayesian logic eludes preliminary
      phase issues in quality control: an example in a hemostasis laboratory.
AB  - The present study seeks to demonstrate the feasibility of avoiding the
      preliminary phase, which is mandatory in all conventional approaches for internal
      quality control (IQC) management. Apart from savings on the resources consumed by
      the preliminary phase, the alternative approach described here is able to detect
      any analytic problems during the startup and provide a foundation for subsequent
      conventional assessment. A new dynamically updated predictive control chart (PCC)
      is used. Being Bayesian in concept, it utilizes available prior information. The
      manufacturer's prior quality control target value, the manufacturer's maximum
      acceptable interassay coefficient of variation value and the interassay standard
      deviation value defined during method validation in each laboratory, allow online
      IQC management. An Excel template, downloadable from journal website, allows easy
      implementation of this alternative approach in any laboratory. In the practical
      case of prothrombin percentage measurement, PCC gave no false alarms with respect
      to the 1ks rule (with same 5% false-alarm probability on a single control sample)
      during an overlap phase between two IQC batches. Moreover, PCCs were as effective
      as the 1ks rule in detecting increases in both random and systematic error after
      the minimal preliminary phase required by medical biology guidelines. PCCs can
      improve efficiency in medical biology laboratories. 

PMID- 25978119
TI  - Anemia and Inflammation in ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: To investigate the factors predicting the onset of major adverse
      cardiovascular events (MACEs) after primary percutaneous coronary intervention
      for ST-segment elevation myocardial infarction (STEMI) patients. METHODS: Two
      hundred forty-eight STEMI patients (61.4 +/- 10.8 years, 186 men) who underwent
      successful primary percutaneous coronary intervention were enrolled. Patients
      were followed-up for 1 year. Univariate, multivariate analyses, and receiver
      operating characteristic curve analysis were performed to determine the factors
      predicting MACEs. RESULTS: There were 36 patients (14.5%) who experienced MACEs
      in the follow-up period. Multivariate logistic regression analysis demonstrated
      that hemoglobin (HgB) (odds ratio = 0.972; 95% CI, 0.948-0.998; P = 0.033),
      neutrophil/lymphocyte ratio (NLR) (odds ratio = 1.511; 95% CI, 1.148-1.987; P =
      0.003), Global Registry of Acute Coronary Event score, and postprocedure left
      ventricular ejection fraction (LVEF) were independent predictors of MACEs.
      Further subgroup analysis showed higher NLR (> 8.61), Global Registry of Acute
      Coronary Event score (> 167) and lower HgB (< 131 g/L) all show superior
      predictive value for patients with relatively higher LVEF (> 48%); moreover, the
      c-statistic of NLR and HgB both exceed 0.7. However, among patients with lower
      LVEF (<= 48%), higher NLR and lower HgB lost the ability for predicting 1 year
      MACEs independently. In addition, abnormally higher NLR (> 8) could predict 1
      month MACEs efficiently. CONCLUSIONS: In summary, among STEMI patients, elevated
      NLR, decreased HgB level on admission both predicted 1-year MACEs independently,
      especially for those with relatively preserved LVEF (> 48%). Besides, abnormally
      higher NLR on admission should attract their attention for short-term MACEs.

PMID- 25978122
TI  - Sophisticated oil film geometries through incomplete electrical dewetting by
      feedback control and Fourier construction.
AB  - Existing techniques for electronic control of the interface between two
      immiscible fluids are typically limited to simple periodic geometries (symmetric
      waves) or spherical geometries (only two principle radii of curvature). Presented
      here, is a new technique with much more sophisticated electronic control of fluid
      meniscus geometry. Previously undemonstrated two-fluid interfaces, such as
      asymmetric saw-tooth profiles, are created by dynamic modulation of an incomplete
      dewetting state for an oil film covering an array of control electrodes, with the
      oil film itself covered by an electrically conductive fluid acting as the ground
      electrode. Two distinct approaches are demonstrated: (1) application of voltages,
      electrical capacitance sensing of meniscus geometry, followed by further feedback
      control of the applied voltages based on the sensed electrical capacitance; (2)
      use of multiple periodic voltage waveforms and wave propagation across the
      meniscus to build up complex meniscus geometries by Fourier construction. These
      approaches are demonstrated in this work by a proven electro-hydrodynamic
      modeling method, which couples the Maxwell stress tensor with the laminar phase
      field of the oil-water dual phase. This work could serve numerous applications
      including particle or fluid transport (e.g. lab-on-chip), or adaptive optical
      surfaces (e.g. liquid prism arrays). Importantly, the results can be achieved
      using conventional materials, and the fluids respond with speeds that are
      adequately slow (ms-MUs) such that even conventional control electronics (MUs-ns)
      are more than adequate. Furthermore, because the conducting fluid never dewets
      the oil film from the solid surface, dielectric degradation issues are likely
      eliminated. 

PMID- 25978123
TI  - Organotin(IV) based anti-HCV drugs: synthesis, characterization and biochemical
      activity.
AB  - Three new organotin(iv) carboxylates () of 3,5-dimethylbenzoate, have been
      synthesized and characterized by elemental analysis, FT-IR, multinuclear NMR
      ((1)H, (13)C and (119)Sn), mass spectrometry and single crystal X-ray structural
      analysis. Crystallographic data show that in compounds and , the geometry at the
      central Sn atom is skew-trapezoidal bipyramidal while compound displays a
      distorted trigonal bipyramidal coordination geometry. In the case of compounds
      and , the asymmetric chelating mode of the carboxylate groups is reflected in the
      unequal C-O bond distances, those observed for the O1 and O3 oxygen atoms being
      significantly longer than those found in the O2 and O4 atoms. In the case of
      compound , the carboxylate groups bridge asymmetrically adjacent tin atoms in an
      anti-syn mode generating polymeric zigzag chains running parallel to the
      crystallographic c-axis. The compounds were screened for anti-HCV (hepatitis C
      virus) potency by the Gaussia luciferase assay using infected Huh 7.5 cells
      (human hepatocellular cell). Structure-activity relationship studies led to the
      identification of dibutyltin(iv)bis(3,5-dimethylbenzoic acid) (compound ) as a
      potent HCV inhibitor, with log IC50 values equal to 0.69 nM in the cell-based
      assay. Compound was further subjected to quantitative analysis using real-time
      PCR assays and viral RNA count vs. drug concentration confirmed the Gaussia
      luciferase assay results. The HCV RNA targeting mode of the compounds () was
      confirmed by a compound-DNA interaction study. The compounds ()-DNA interactions
      were investigated by UV-vis spectroscopy and viscometry. The hypochromic effect
      in spectroscopy evidenced an intercalative mode of interaction with the binding
      affinity in the order of > > . 

PMID- 25978124
TI  - Synthesis of Luffarin L and 16-epi-Luffarin L Using a Temporary Silicon-Tethered
      Ring-Closing Metathesis Reaction.
AB  - The first synthesis of luffarin L (1) and 16-epi-luffarin L (2) by a silicon
      tethered ring closing metathesis as a key step has been achieved. The
      stereochemistry and absolute configuration of the natural sesterterpenolide
      luffarin L (1) and a new route for the stereoselective synthesis of
      sesterterpenolides with a luffarane skeleton have been established. 

PMID- 25978125
TI  - Profound anterograde amnesia following routine anesthetic and dental procedure: a
      new classification of amnesia characterized by intermediate-to-late-stage
      consolidation failure?
AB  - Anterograde amnesia caused by bilateral hippocampal or diencephalon damage
      manifests in characteristic symptoms of preserved intellect and implicit
      learning, and short span of awareness with complete and rapid forgetting of
      episodic material. A new case, WO, 38-year-old male with anterograde amnesia, in
      the absence of structural brain changes or psychological explanation is
      presented, along with four comparison cases from the extant literature that share
      commonalities between them including preserved intellect, span of awareness
      greater than working memory, and complete forgetting within hours or days
      following successful learning, including notably for both explicit and implicit
      material. WO's amnesia onset coincided with anesthetic injection and root canal
      procedure, with extended vasovagal-like incident. The commonalities between the
      five cases presented may suggest a shared biological mechanism involving the
      breakdown of intermediate-to-late-stage consolidation that does not depend on the
      structural integrity of the hippocampi. Speculation on the mechanism of
      consolidation breakdown and diagnostic implications are discussed. 

PMID- 25978126
TI  - Continuous Glucose Monitoring Use in Hospitalized Patients.

PMID- 25978127
TI  - A Paleoparasitological Study on the Capital Area of the Ancient Korean Kingdom.
AB  - A paleoparasitological study was performed on soil samples obtained at
      archaeological sites dating to the Baekje period in ancient Korean history. The
      samples were obtained from Buyeo, the capital area of the Baekje Kingdom, and
      from others corresponding to provincial counties of the same period. We found
      Ascaris lumbricoides and Trichuris trichiura eggs in the Buyeo samples but not
      any in the samples from the provincial counties. Our results suggest that the
      parasite-egg contamination patterns were closely correlated with population
      densities, in that the provincial counties of the Kingdom, compared with the
      capital Buyeo, were very sparsely populated. This is the first comprehensive
      paleoparasitological report on soil contamination patterns in the capital of the
      Baekje Kingdom, one of the most highly populated areas in ancient Korean history.

PMID- 25978129
TI  - Correction to: Zebrafish, 10:3;447-450.

PMID- 25978128
TI  - The dual role of borohydride depending on reaction temperature: synthesis of
      iridium and iridium oxide.
AB  - Temperature dependent reaction products are observed when borohydride is present
      in aqueous solutions containing Ir(3+). At temperatures of 40  degrees C and
      above, metallic iridium is formed while under ambient conditions of 25  degrees
      C, borohydride results in an alkaline environment that helps in hydrolyzing the
      precursor to form IrO2. The Ir foams and IrO2 are subsequently used to study
      their catalytic properties. 

PMID- 25978130
TI  - Reactivity of CO2 Activated on Transition Metals and Sulfur Ligands.
AB  - Dicationic dicarbonyl [Ru(bpy)2(CO)2](2+) (bpy = 2,2'- bipyridyl) exists as
      equilibrium mixtures with [Ru(bpy)2(CO)(COOH)](+) and [Ru(bpy)2(CO)(CO2)](0)
      depending on the pH in H2O. Those three complexes work as the precursors to CO,
      HCOOH production, and CO2 carrier, respectively, in electro- and photochemical
      CO2 reduction in aqueous solutions. However, [Ru(bpy)2(CO)2](2+) loses the
      catalytic activity toward CO2 reduction under aprotic conditions because
      [Ru(bpy)2(CO)2](2+) is not regenerated from [Ru(bpy)2(CO)(CO2)](0) in the absence
      of proton sources. Analogous monocarbonylruthenium complexes such as
      [Ru(tpy)(bpy)(CO)](2+) and [Ru(bpy)2(qu)(CO)](2+) catalyze CO2 reduction in the
      absence and presence of proton sources. Both complexes are reproduced through
      oxide transfer from the corresponding Ru-CO2 to CO2 in CO2 reduction and produce
      the same amount of CO and CO3(2-) in the absence of proton donors. The reduction
      of CO2 catalyzed by polypyridylrhenium complexes in the presence of proton
      sources takes place via essentially the similar mechanism as that in the case of
      ruthenium complexes. On the other hand, CO evolution in CO2 reduction under
      aprotic conditions is ascribed to the dissociation of CO from a dimeric Re
      C(O)OC(O)O-Re scaffold. Visible-light irradiation to a catalytic system composed
      of [Ru(bpy)2(CO)2](2+)/[Ru(bpy)3](2+)/Me2NH2(+)/Me2NH as the catalyst,
      photosensitizer, proton donor, and nucleophile in addition to the electron donor,
      respectively, in CO2-saturated CH3CN selectively produces N,N-dimethylformamide
      without concomitant CO and HCOOH formation. Structurally robust MU3-S of reduced
      metal-sulfur clusters provides a suitable site for reductive activation of CO2
      with retention of the framework. Indeed, CO2 activated on MU3-S of
      [Fe6Mo2S8(SEt)3](5-) is fixed at the carbonyl carbon of thioesters trapped on a
      neighboring iron of the cluster, and alpha-keto acids are produced catalytically.
      Furthermore, two-electron reduction of [(CpMen)3M3S3](2+) (n = 1, M = Co; n = 5,
      M = Rh, Ir) creates the catalytic ability to produce oxalate through the coupling
      of two CO2 molecules possibly activated on MU3-S and a metal ion. 

PMID- 25978132
TI  - Identification of Oxaphenalenone Ketals from the Ascomycete Fungus Neonectria sp.
AB  - Neonectrolides B-E (4-7), four new oxaphenalenone ketals incorporating the new
      furo[2,3-b]isochromeno[3,4,5-def]chromen-11(6aH)-one skeleton, were isolated from
      the fermentation extract of the ascomycete fungus Neonectria sp. in an in-depth
      investigation guided by HPLC fingerprint and a cytotoxicity assay. The previously
      identified oxaphenalenone spiroketal neonectrolide A (1) and its putative
      biosynthetic precursors (2 and 3) were also reisolated in the current work. The
      structures of 4-7 were primarily elucidated by interpretation of NMR
      spectroscopic data, and the absolute configurations were deduced by electronic
      circular dichroism calculations. Compound 6 showed cytotoxic effects against four
      of the six human tumor cell lines tested. Biosynthetically, compounds 4-7 could
      be derived via the Diels-Alder reaction cascades starting from derivatives of the
      co-isolated metabolites 2 and 3. 

PMID- 25978131
TI  - The therapeutic advantage of combination antihypertensive drug therapy using
      amlodipine and irbesartan in hypertensive patients: Analysis of the post
      marketing survey data from PARTNER (Practical combination therapy of Amlodin and
      angiotensin II Receptor blocker; safety and efficacy in patients with
      hypertension) study.
AB  - Two-thirds of hypertensive patients need a combination antihypertensive therapy
      to achieve the target blood pressure (BP). The PARTNER (Practical combination
      therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in
      paTieNts with hypERtension) study is a prospective specific clinical use survey
      examining the efficacy and safety of 12-week treatment with amlodipine (AML) and
      Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current
      analysis was performed as to the BP control, adverse reactions, and the effects
      on laboratory data in patients treated with the combination of AML and irbesartan
      (IRB), namely the patients added AML to already taking IRB (AML add-on group, n =
      1202) and the patients added IRB to AML (IRB add-on group, n = 1050). Both study
      groups showed distinct decreases in office BP at 4 week (p < 0.001) and the
      antihypertensive effects were sustained to 12 week (p < 0.001). The percentage of
      patients achieving BP < 140/90 mmHg was ~70% in either group. Proteinuria and
      estimated glomerular filtration rate (eGFR) were significantly improved in
      hypertensive patients with baseline eGFR <60 ml/min/1.73 m(2). Serum uric acid
      was reduced either by adding AML or IRB, and the reductions were prominent in
      patients with serum uric acid >7 mg/dl. The incidence of adverse reactions was as
      few as 1.11% and there were no severe adverse reactions which hampered the
      continuation of combination therapy. In conclusion, combination antihypertensive
      therapy with AML and IRB effectively lowers BP without particular safety
      problems, reduces serum uric acid especially in patients with hyperuricemia and
      exhibits renoprotective effects in patients with chronic kidney disease. 

PMID- 25978133
TI  - Cell-targeted platinum nanoparticles and nanoparticle clusters.
AB  - Herein, we report the facile preparation of cell-targeted platinum nanoparticles
      (PtNPs), through the design of peptides that, as a single molecule added in small
      concentration during the synthesis, control the size of PtNP clusters during
      their growth, stabilise the PtNPs in aqueous suspension and enable the
      functionalisation of the PtNPs with a versatile range of cell-targeting ligands.
      Water-soluble PtNPs targeted respectively at blood group antigens and at integrin
      receptors are demonstrated. 

PMID- 25978134
TI  - Insecticidal properties of essential oils against Tribolium castaneum (Herbst)
      and their inhibitory effects on acetylcholinesterase and adenosine
      triphosphatases.
AB  - Essential oils from 20 Egyptian plants were obtained by using hydrodistillation.
      The chemical composition of the isolated oils was identified by gas
      chromatograph/mass spectrometer. Fumigant and contact toxicities of the essential
      oils were evaluated against the adults of Tribolium castaneum. In fumigation
      assays, the oil of Origanum vulgare (LC50 = 9.97 mg/L air) displayed the highest
      toxicity towards the adults of T. castaneum. In contact assays, the oils of
      Artemisia monosperma (LC50 = 0.07 mg/cm(2)) and O. vulgare (LC50 = 0.07 mg/cm(2))
      were the most potent toxicants against the adults of T. castaneum. Biochemical
      studies showed that the tested oils caused pronounced inhibition of
      acetylcholinesterase (AChE) and adenosine triphosphatases (ATPases) isolated from
      the larvae of T. castaneum. The oil Cupressus macrocarpa (IC50 = 12.3 mg/L) was
      the most potent inhibitor of AChE, while the oil of Calistemon viminals (IC50 =
      4.4 mg/L) was the most potent inhibitor of ATPases.

PMID- 25978135
TI  - Explicit solvent simulations of the aqueous oxidation potential and
      reorganization energy for neutral molecules: gas phase, linear solvent response,
      and non-linear response contributions.
AB  - First principles simulations were used to predict aqueous one-electron oxidation
      potentials (Eox) and associated half-cell reorganization energies (lambdaaq) for
      aniline, phenol, methoxybenzene, imidazole, and dimethylsulfide. We employed
      quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD)
      simulations of the oxidized and reduced species in an explicit aqueous solvent,
      followed by EOM-IP-CCSD computations with effective fragment potentials for
      diabatic energy gaps of solvated clusters, and finally thermodynamic integration
      of the non-linear solvent response contribution using classical MD. A priori
      predicted Eox and lambdaaq values exhibit mean absolute errors of 0.17 V and 0.06
      eV, respectively, compared to experiment. We also disaggregate Eox into several
      well-defined free energy properties, including the gas phase adiabatic free
      energy of ionization (7.73 to 8.82 eV), the solvent-induced shift in the free
      energy of ionization due to linear solvent response (-2.01 to -2.73 eV), and the
      contribution from non-linear solvent response (-0.07 to -0.14 eV). The linear
      solvent response component is further apportioned into contributions from the
      solvent-induced shift in vertical ionization energy of the reduced species
      (DeltaVIEaq) and the solvent-induced shift in negative vertical electron affinity
      of the ionized species (DeltaNVEAaq). The simulated DeltaVIEaq and DeltaNVEAaq
      are found to contribute the principal sources of uncertainty in computational
      estimates of Eox and lambdaaq. Trends in the magnitudes of disaggregated
      solvation properties are found to correlate with trends in structural and
      electronic features of the solute. Finally, conflicting approaches for evaluating
      the aqueous reorganization energy are contrasted and discussed, and concluding
      recommendations are given. 

PMID- 25978136
TI  - New pimarane diterpenes and other antimycobacterial metabolites from Anisochilus
      verticillatus.
AB  - Phytochemical investigation of the acetone extract of the aerial parts of
      Anisochilus verticillatus afforded a new 8,9-secopimarane diterpene (1), two new
      isopimarane diterpenes (2, 3) and the known ursolic acid (4), alpha-amyrin (5),
      beta-amyrin (6), stigmast-5-en-3-one (7) and hydroxychavicol (8). Structures of
      the new compounds were elucidated with the help of 1D and 2D nuclear magnetic
      resonance spectroscopic data, and single crystal X-ray crystallography of
      compound 3. Compounds 2 and 8 inhibited Mycobacterium tuberculosis H37Ra with an
      IC50 of 11.3 (IC90 of 20.0 MUg/mL) and 12.5 MUg/mL, respectively.
      Correspondingly, molecular docking studies with Extra Precision Glide revealed a
      correlation between score and biological activity for these compounds to describe
      the molecular basis for the most significant SAR results.

PMID- 25978137
TI  - Effects of selenium on endothelial dysfunction and metabolic profile in low dose
      streptozotocin induced diabetic rats fed a high fat diet.
AB  - Endothelial dysfunction develops as a result of oxidative stress and is
      responsible for diabetic vascular complications. We investigated the effects of
      selenium on endothelial dysfunction and oxidative stress in type 2 diabetic rats.
      Male Wistar rats were divided into five groups: controls, untreated diabetics,
      and diabetics treated with 180, 300, 500 mcg/kg selenium each day. Diabetes was
      induced by a single intraperitoneal injection of low dose streptozotocin to rats
      fed a high fat diet. Endothelium-dependent and -independent relaxations were
      measured in the thoracic aorta. Nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase and endothelial nitric oxide synthase (eNOS) mRNA expressions
      were analyzed using real-time polymerase chain reaction (RT-PCR). Fasting blood
      glucose, lipid profile, lipid oxidation, insulin and nitric oxide were measured
      in blood samples. Malondialdehyde, superoxide dismutase, catalase and glutathione
      peroxidase levels were measured in liver samples. RT-PCR showed that selenium
      reversed increased NADPH oxidase expression and decreased eNOS expression to
      control levels. Selenium also improved the impairment of endothelium-dependent
      vasorelaxation in the diabetic aorta. Selenium treatment significantly decreased
      blood glucose, cholesterol and triglyceride levels, and enhanced the antioxidant
      status in diabetic rats. Our findings suggest that selenium restores a normal
      metabolic profile and ameliorates vascular responses and endothelial dysfunction
      in diabetes by regulating antioxidant enzyme and nitric oxide release. 

PMID- 25978138
TI  - A biochemical and immunohistochemical study of the protective effects of
      carnosine for carbon tetrachloride induced liver injury in rats.
AB  - We investigated the protective effect of carnosine on carbon tetrachloride
      induced liver tissue damage. Thirty-two adult male rats were divided into four
      equal groups. Group 1 was the untreated control, group 2 was injected with 0.2
      ml/kg/day carbon tetrachloride, group 3 was injected with with 0.2 ml/kg/day
      carbon tetrachloride plus 200 mg/kg/day carnosine, and group 4 was injected with
      200 mg/kg/day carnosine. Increased serum alanine amino transferase and aspartate
      amino transferase levels, liver malondialdehyde levels, HSP-70 expression and
      steatosis were observed following treatment with carbon tetrachloride. Carbon
      tetrachloride caused severe biochemical and histopathological changes in liver
      tissue and treatment with carnosine partially prevented the damage. HSP-70 may
      help control liver damage. 

PMID- 25978139
TI  - Applications and challenges of digital pathology and whole slide imaging.
AB  - Virtual microscopy is a method for digitizing images of tissue on glass slides
      and using a computer to view, navigate, change magnification, focus and mark
      areas of interest. Virtual microscope systems (also called digital pathology or
      whole slide imaging systems) offer several advantages for biological scientists
      who use slides as part of their general, pharmaceutical, biotechnology or
      clinical research. The systems usually are based on one of two methodologies:
      area scanning or line scanning. Virtual microscope systems enable automatic
      sample detection, virtual-Z acquisition and creation of focal maps. Virtual
      slides are layered with multiple resolutions at each location, including the
      highest resolution needed to allow more detailed review of specific regions of
      interest. Scans may be acquired at 2, 10, 20, 40, 60 and 100 * or a combination
      of magnifications to highlight important detail. Digital microscopy starts when a
      slide collection is put into an automated or manual scanning system. The original
      slides are archived, then a server allows users to review multilayer digital
      images of the captured slides either by a closed network or by the internet. One
      challenge for adopting the technology is the lack of a universally accepted file
      format for virtual slides. Additional challenges include maintaining focus in an
      uneven sample, detecting specimens accurately, maximizing color fidelity with
      optimal brightness and contrast, optimizing resolution and keeping the images
      artifact-free. There are several manufacturers in the field and each has not only
      its own approach to these issues, but also its own image analysis software, which
      provides many options for users to enhance the speed, quality and accuracy of
      their process through virtual microscopy. Virtual microscope systems are widely
      used and are trusted to provide high quality solutions for teleconsultation,
      education, quality control, archiving, veterinary medicine, research and other
      fields. 

PMID- 25978140
TI  - BMP-2-induced Neuroforaminal Bone Growth in the Setting of a Minimally Invasive
      Transforaminal Lumbar Interbody Fusion.
AB  - Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has become a
      popular alternative to traditional methods of lumbar decompression and fusion.
      When compared with the open technique, the minimally invasive approach can result
      in decreased pain and blood loss as well as a shorter length of hospitalization.
      However, the narrower working channel through the tubular retractor increases the
      difficulty of decortication and bone grafting. Therefore, recombinant human bone
      morphogenetic proteins (rhBMP-2) is often utilized (although this is off-label)
      to create a more favorable interbody fusion environment. Recently, the use of
      rhBMP-2 has been associated with excessive bone growth in an MIS-TLIF. If this
      bone growth compresses the neighboring neural structures, patients may present
      with either new or recurrent radicular pain. Computed tomographic (CT) imaging
      can demonstrate heterotopic bone growth extending from the disk space into either
      the ipsilateral neuroforamen or lateral recess, which may result in the
      compression of the exiting or traversing root, respectively. The purpose of this
      article and the accompanying video is to demonstrate a technique for defining and
      resecting rhBMP-2-induced heterotopic bone growth following a previous MIS-TLIF. 

PMID- 25978141
TI  - Biologics in spine arthrodesis.
AB  - Spine fusion is a tool used in the treatment of spine trauma, tumors, and
      degenerative disorders. Poor outcomes related to failure of fusion, however, have
      directed the interests of practitioners and scientists to spinal biologics that
      may impact fusion at the cellular level. These biologics are used to achieve
      successful arthrodesis in the treatment of symptomatic deformity or instability.
      Historically, autologous bone grafting, including iliac crest bong graft
      harvesting, had represented the gold standard in spinal arthrodesis. However, due
      to concerns over potential harvest site complications, supply limitations, and
      associated morbidity, surgeons have turned to other bone graft options known for
      their osteogenic, osteoinductive, and/or osteoconductive properties. Current bone
      graft selection includes autograft, allograft, demineralized bone matrix,
      ceramics, mesenchymal stem cells, and recombinant human bone morphogenetic
      protein. Each pose their respective advantages and disadvantages and are the
      focus of ongoing research investigating the safety and efficacy of their use in
      the setting of spinal fusion. Rh-BMP2 has been plagued by issues of widespread
      off-label use, controversial indications, and a wide range of adverse effects.
      The risks associated with high concentrations of exogenous growth factors have
      led to investigational efforts into nanotechnology and its application in spinal
      arthrodesis through the binding of endogenous growth factors. Bone graft
      selection remains critical to successful fusion and favorable patient outcomes,
      and orthopaedic surgeons must be educated on the utility and limitations of
      various biologics in the setting of spine arthrodesis.

PMID- 25978142
TI  - Evaluation of Titanium Dioxide as a Binding Phase for the Passive Sampling of
      Glyphosate and Aminomethyl Phosphonic Acid in an Aquatic Environment.
AB  - Glyphosate is the most widely used herbicide on a world scale for the last 40
      years, for both urban and agricultural uses. Here we describe the first passive
      sampling method for estimating the concentration of glyphosate and AMPA
      (aminomethyl phosphonic acid, one of its major degradation products) in surface
      water. The sampling method is based on a newly developed configuration of the
      diffusive gradient in thin-film (DGT) technique, which includes a TiO2 binding
      phase, already in use for a wide range of anions. Glyphosate and AMPA were
      retained well on a TiO2 binding phase, and elution in a 1 mL of 1 M NaOH led to
      recoveries greater than 65%. We found no influence of pH or flow velocity on the
      diffusion coefficients through 0.8 mm polyacrylamide gels, although they did
      increase with temperature. TiO2 binding gels were able to accumulate up to 1167
      ng of P for both glyphosate and AMPA, and linear accumulation was expected over
      several weeks, depending on environmental conditions. DGT sampling rates were
      close to 10 mL day(-1) in ultrapure water, while they were less than 1 mL day(-1)
      in the presence of naturally occurring ions (e.g., copper, iron, calcium,
      magnesium). These last results highlighted (i) the ability of DGT to measure only
      the freely dissolved fraction of glyphosate and AMPA in water and (ii) the needs
      to determine which fraction (total, particulate, dissolved, freely dissolved) is
      indeed bioactive. 

PMID- 25978143
TI  - Asymmetric Supercapacitors Using 3D Nanoporous Carbon and Cobalt Oxide Electrodes
      Synthesized from a Single Metal-Organic Framework.
AB  - Nanoporous carbon and nanoporous cobalt oxide (Co3O4) materials have been
      selectively prepared from a single metal-organic framework (MOF) (zeolitic
      imidazolate framework, ZIF-67) by optimizing the annealing conditions. The
      resulting ZIF-derived carbon possesses highly graphitic walls and a high specific
      surface area of 350 m(2).g(-1), while the resulting ZIF-derived nanoporous Co3O4
      possesses a high specific surface area of 148 m(2).g(-1) with much less carbon
      content (1.7 at%). When nanoporous carbon and nanoporous Co3O4 were tested as
      electrode materials for supercapacitor application, they showed high capacitance
      values (272 and 504 F.g(-1), respectively, at a scan rate of 5 mV.s(-1)). To
      further demonstrate the advantages of our ZIF-derived nanoporous materials,
      symmetric (SSCs) and asymmetric supercapacitors (ASCs) were also fabricated using
      nanoporous carbon and nanoporous Co3O4 electrodes. Improved capacitance
      performance was successfully realized for the ASC (Co3O4//carbon), better than
      those of the SSCs based on nanoporous carbon and nanoporous Co3O4 materials
      (i.e., carbon//carbon and Co3O4//Co3O4). The developed ASC with an optimal mass
      loading can be operated within a wide potential window of 0.0-1.6 V, which leads
      to a high specific energy of 36 W.h.kg(-1). More interestingly, this ASC also
      exhibits excellent rate capability (with the highest specific power of 8000 W.kg(
      1) at a specific energy of 15 W.h.kg(-1)) combined with long-term stability up to
      2000 cycles. 

PMID- 25978144
TI  - Formation and frequency response of two-dimensional nanowire lattices in an
      applied electric field.
AB  - Ordered two-dimensional (2D) lattices were formed by assembling silica-coated
      solid and segmented Au nanowires between coplanar electrodes using alternating
      current (ac) electric fields. Dielectrophoretic forces from the ac field
      concentrated wires between the electrodes, with their long axis aligned parallel
      to the field lines. After reaching a sufficient particle density, field-induced
      dipolar interactions resulted in the assembly of dense 2D lattices that spanned
      the electrodes, a distance of at least ten wire lengths. The ends of neighboring
      Au wires or segments overlapped a fraction of their length to form lattice
      structures with a "running bond" brickwork-like pattern. The observed lattice
      structures were tunable in three distinct ways: (1) particle segmentation
      pattern, which fixed the lattice periodicity for a given field condition; (2) ac
      frequency, which varied lattice periodicity in real time; and (3) switching the
      field on/off, which converted between lattice and smectic particle organizations.
      Electric field simulations were performed to understand how the observed lattice
      periodicity depends on the assembly conditions and particle segmentation.
      Directed self-assembly of well-ordered 2D metallic nanowire lattices that can be
      designed by Au striping pattern and reconfigured by changes in field conditions
      could enable new types of switchable optical or electronic devices. 

PMID- 25978145
TI  - Evaluation of Genetically Encoded Chemical Tags as Orthogonal Fluorophore
      Labeling Tools for Single-Molecule FRET Applications.
AB  - Fluorescence resonance energy transfer (FRET) is a superb technique for measuring
      conformational changes of proteins on the single molecule level (smFRET) in real
      time. It requires introducing a donor and acceptor fluorophore pair at specific
      locations on the protein molecule of interest, which has often been a challenging
      task. By using two different self-labeling chemical tags, such as Halo-, TMP-,
      SNAP- and CLIP-tags, orthogonal labeling may be achieved rapidly and reliably.
      However, these comparatively large tags add extra distance and flexibility
      between the desired labeling location on the protein and the fluorophore
      position, which may affect the results. To systematically characterize chemical
      tags for smFRET measurement applications, we took the SNAP-tag/CLIP-tag
      combination as a model system and fused a flexible unstructured peptide, rigid
      polyproline peptides of various lengths, and the calcium sensor protein
      calmodulin between the tags. We could reliably identify length variations as
      small as four residues in the polyproline peptide. In the calmodulin system, the
      added length introduced by these tags was even beneficial for revealing subtle
      conformational changes upon variation of the buffer conditions. This approach
      opens up new possibilities for studying conformational dynamics, especially in
      large protein systems that are difficult to specifically conjugate with
      fluorophores. 

PMID- 25978146
TI  - Occupational exposures to radiofrequency fields: results of an Israeli national
      survey.
AB  - Relatively high exposures to radiofrequency (RF) fields can occur in the
      broadcast, medical, and communications industries, as well in occupations that
      use RF emitting equipment (e.g. law enforcement). Information on exposure to
      workers employed in these industries and occupations is limited. We present
      results of an Israeli National Survey of occupational RF field levels at
      frequencies between ~100 kHz and 40 GHz, representing Industrial Heating,
      Communications, Radar, Research, and Medicine. Almost 4300 measurements from 900
      sources across 25 occupations were recorded and categorised as 'routine',
      'incidental', or 'unintended'. The occupation-specific geometric means (GMs) of
      the percentage of the American Conference of Governmental Industrial Hygienists
      (ACGIH) threshold limit values (TLVs) for each of the three exposure scenarios
      are presented together with the geometric standard deviation (GSD). Additionally,
      we present estimates of occupation-specific annual personal exposures and
      collective exposures. The vast majority of the GM of routine exposures ranged
      from a fraction to less than 1% of ACGIH TLVs, except for Walkie-Talkie (GM 94%
      of ACGIH), Induction Heating (17%), Plastic Welding (11%), Industrial Heating
      (6%) and Diathermy (6%). The GM of incidental and unintended exposures exceeded
      the TLV for one and 14 occupations, respectively. In many cases, the within
      occupation GSD was very large, and though the medians remained below TLV,
      variable fractions of these occupations were projected to exceed the TLV. In rank
      order, Walkie-Talkie, Plastic Welding, and Induction Heating workers had the
      highest annual cumulative personal exposure. For cumulative collective exposures
      within an occupation, Walkie-Talkie dominated with 96.3% of the total, reflecting
      both large population and high personal exposure. A brief exceedance of the TLV
      does not automatically translate to hazard as RF exposure limits (issued by
      various bodies, including ACGIH) include a 10-fold safety factor relative to
      thermal thresholds and are based on a 6 min averaging period.

PMID- 25978147
TI  - Paclitaxel-induced pneumonitis in patients with breast cancer: case series and
      review of the literature.
AB  - Doxorubicin plus cyclophosphamide followed by paclitaxel is a common adjuvant
      treatment for high-risk breast cancer. It has been associated with pulmonary
      toxicity in several case reports. We describe three patients in whom interstitial
      pneumonitis developed immediately after the first paclitaxel exposure and
      worsened clinically over time. All reported dyspnoea, fever and progressive
      respiratory distress. Imaging revealed diffuse bilateral pulmonary infiltrates.
      Other causes of respiratory failure were excluded with laboratory work-up,
      imaging, biopsy studies and results of antibiotic treatment. The respiratory
      decline was reversed only after administration of high-dose steroids, an
      empirical treatment previously reported to be beneficial in similar cases.
      Although chemotherapy using concomitant or sequential drugs may make
      identification of the toxic agent difficult, we noted a clear temporal
      relationship between exposure to paclitaxel and the development of pulmonary
      toxicity. Furthermore, according to the available literature, it is less likely
      that a respiratory decline would be caused by either cyclophosphamide or
      trastuzumab. In conclusion, clinicians should be aware of the potentially life
      threatening risk of pulmonary toxicity following paclitaxel treatment. If
      paclitaxel is halted early and the patient has good lung reserve, pulmonary
      toxicity can be reversed with high-dose steroid administration.

PMID- 25978148
TI  - High-Temperature Experimental and Theoretical Study of the Unimolecular
      Dissociation of 1,3,5-Trioxane.
AB  - Unimolecular dissociation of 1,3,5-trioxane was investigated experimentally and
      theoretically over a wide range of conditions. Experiments were performed behind
      reflected shock waves over the temperature range of 775-1082 K and pressures near
      900 Torr using a high-repetition rate time of flight mass spectrometer (TOF-MS)
      coupled to a shock tube (ST). Reaction products were identified directly, and it
      was found that formaldehyde is the sole product of 1,3,5-trioxane dissociation.
      Reaction rate coefficients were extracted by the best fit to the experimentally
      measured concentration-time histories. Additionally, high-level quantum chemical
      and RRKM calculations were employed to study the falloff behavior of 1,3,5
      trioxane dissociation. Molecular geometries and frequencies of all species were
      obtained at the B3LYP/cc-pVTZ, MP2/cc-pVTZ, and MP2/aug-cc-pVDZ levels of theory,
      whereas the single-point energies of the stationary points were calculated using
      coupled cluster with single and double excitations including the perturbative
      treatment of triple excitation (CCSD(T)) level of theory. It was found that the
      dissociation occurs via a concerted mechanism requiring an energy barrier of 48.3
      kcal/mol to be overcome. The new experimental data and theoretical calculations
      serve as a validation and extension of kinetic data published earlier by other
      groups. Calculated values for the pressure limiting rate coefficient can be
      expressed as log10 kinfinity (s(-1)) = [15.84 - (49.54 (kcal/mol)/2.3RT)] (500
      1400 K). 

PMID- 25978149
TI  - The influence of yttrium dopant on the properties of anatase nanoparticles and
      the performance of dye-sensitized solar cells.
AB  - TiO2 mesoporous nanoparticles (NPs) doped with yttrium (Y) ions are fabricated
      via an environmentally friendly and facile solvothermal method to serve as a
      photoanode for dye sensitized solar cells (DSSCs). X-ray diffraction, X-ray
      photoelectron spectroscopy, transmission electron microscopy and N2 adsorption
      desorption tests are used to characterize the influence of yttrium dopant on the
      properties of TiO2 NPs. The prepared Y-doped TiO2 NPs show the anatase phase and
      exhibit Ti-O-Y bonds. The photovoltaic performance is primarily associated with
      the morphological parameters of the NPs. At the optimum Y concentration of 3 at%,
      the short circuit current density increased from 13.20 to 15.74 mA cm(-2), full
      sun solar power conversion efficiencies increased from 6.09% up to 7.61% as
      compared to the blank DSSC. 

PMID- 25978150
TI  - Hollow Ball-in-Ball CoxFe3-xO4 Nanostructures: High-Performance Anode Materials
      for Lithium-Ion Battery.
AB  - The intrinsic electronic conductivity can be improved by doping efficiently.
      CoxFe3-xO4 nanostructures have been synthesized for the first time to improve the
      conductivity of lithium battery electrode. The solid solution CoxFe3--xO4 were
      characterized by X-ray diffraction pattern (XRD), Raman spectrum, scanning
      electron microscopy (SEM), transmission electron microscope (TEM),
      electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). The
      results show that the doping enlarge the lattice spacing but the structure of
      Co3O4 is stable in the Li-ion intercalation/deintercalation process. The AC
      impedance spectrum reveals the conductivity is well improved. In addition, the
      solid solution CoxFe3-xO4 exhibit excellent electrochemical characteristics. The
      electrodes with 20% molar ratio of Fe ions own a reversible capacity of 650.2 mA
      h g(-1) at a current density of 1 A g(-1) after 100 cycles. 

PMID- 25978151
TI  - Evaluation of the Clinical Usefulness of BRAFV600E Mutation Analysis of Core
      Needle Biopsy Specimens in Thyroid Nodules with Previous Atypia of Undetermined
      Significance or Follicular Lesions of Undetermined Significance Results.
AB  - BACKGROUND: The accurate diagnosis of thyroid nodules is important for making
      management decisions. The purpose of this study is to evaluate the clinical
      usefulness of BRAF(V600E) mutation analysis with core-needle biopsy
      (CNB+BRAF(V600E)) in thyroid nodules with previous atypia of undetermined
      significance (AUS) or follicular lesions of undetermined significance (FLUS)
      results. MATERIALS AND METHODS: From January 2011 to December 2012, 590
      CNB+BRAF(V600E) mutation analyses were performed. We analyzed 200 nodules from
      200 patients with previous AUS/FLUS results (22 men, 178 women; mean age, 48.6
      years). The clinical usefulness of CNB+BRAF(V600E) was assessed by comparing the
      rates of conclusive results, the additional value of BRAF(V600E) mutation
      analysis, diagnostic performances, and therapeutic/diagnostic surgery results
      with those of CNB alone. For the subgroup analysis, the study patients were
      divided into those with nodules with previous AUS results and those with previous
      FLUS results. RESULTS: All CNB+BRAF(V600E) procedures were well-tolerated.
      CNB+BRAF(V600E) did not show significantly better diagnostic performance than CNB
      alone in thyroid nodules with previous AUS/FLUS results. However, the conclusive
      result rate of CNB+BRAF(V600E) was improved in thyroid nodules with previous
      AUS/FLUS results (76.5% vs. 73.0%, p=0.016), especially with previous AUS results
      (81.1% vs. 76.4%, p=0.031). Of the 56 previous AUS result thyroid nodules with
      surgical management, BRAF(V600E) mutation analysis led to therapeutic surgery in
      5.4% by decreasing unnecessary diagnostic surgery. CONCLUSIONS: In general,
      CNB+BRAF(V600E) did not show significantly higher diagnostic accuracy than CNB
      alone. Although CNB+BRAF(V600E) may add additional value in nodules with previous
      AUS results, routinely adding BRAF(V600E) mutation analysis to CNB is not
      recommended.

PMID- 25978152
TI  - Differences in Paramedic Fatigue before and after Changing from a 24-hour to an 8
      hour Shift Schedule: A Case Report.
AB  - Emergency medical services (EMS) clinicians often work 24-hour shifts. There is a
      growing body of literature, with an elevated level of concern among EMS leaders
      that longer shifts contribute to fatigued workers and negative safety outcomes.
      However, many questions remain about shift length, fatigue, and outcomes. We
      describe a case of a 26-year-old male paramedic who switched shift schedules
      during the midpoint of a randomized trial that addressed fatigue in EMS workers
      (clinicaltrials.gov identifier: NCT02063737). The participant (case) began the
      study working full-time with a critical care, advanced life support EMS system
      that utilized 24-hour shifts. He then transitioned to an EMS system that deploys
      workers on 8-hour shifts. Per protocol for the randomized trial, the participant
      completed a battery of sleep health and fatigue surveys at baseline and at the
      end of 90 days of study. He also reported perceived fatigue, sleepiness, and
      difficulty with concentration at the beginning, every 4 hours during, and at the
      end of scheduled shifts, for a total of ten 24-hour shifts and twenty-four 8-hour
      shifts. We discuss differences in measures taken before and after switching shift
      schedules, and highlight differences in fatigue, sleepiness, and difficulty with
      concentration taken at the end of all 34 scheduled shifts stratified by shift
      duration (24 hours versus 8 hours). Findings from this case report present a
      unique opportunity to 1) observe and analyze a phenomenon that has not been
      investigated in great detail in the EMS setting; and 2) address an issue of
      significance to employers and EMS clinicians alike.

PMID- 25978153
TI  - Bad bugs, no drugs: are we part of the problem, or leaders in developing
      solutions?

PMID- 25978155
TI  - Critical care management of two patients with Ebola: a biocontainment unit
      demystified.

PMID- 25978154
TI  - Management of the Potential Organ Donor in the ICU: Society of Critical Care
      Medicine/American College of Chest Physicians/Association of Organ Procurement
      Organizations Consensus Statement.
AB  - This document was developed through the collaborative efforts of the Society of
      Critical Care Medicine, the American College of Chest Physicians, and the
      Association of Organ Procurement Organizations. Under the auspices of these
      societies, a multidisciplinary, multi-institutional task force was convened,
      incorporating expertise in critical care medicine, organ donor management, and
      transplantation. Members of the task force were divided into 13 subcommittees,
      each focused on one of the following general or organ-specific areas: death
      determination using neurologic criteria, donation after circulatory death
      determination, authorization process, general contraindications to donation,
      hemodynamic management, endocrine dysfunction and hormone replacement therapy,
      pediatric donor management, cardiac donation, lung donation, liver donation,
      kidney donation, small bowel donation, and pancreas donation. Subcommittees were
      charged with generating a series of management-related questions related to their
      topic. For each question, subcommittees provided a summary of relevant literature
      and specific recommendations. The specific recommendations were approved by all
      members of the task force and then assembled into a complete document. Because
      the available literature was overwhelmingly comprised of observational studies
      and case series, representing low-quality evidence, a decision was made that the
      document would assume the form of a consensus statement rather than a formally
      graded guideline. The goal of this document is to provide critical care
      practitioners with essential information and practical recommendations related to
      management of the potential organ donor, based on the available literature and
      expert consensus. 

PMID- 25978156
TI  - Increased mortality in "cold sepsis": the result of a frozen immune response?

PMID- 25978157
TI  - We May Be Using ICU Inefficiently for Patients With Severe Pneumonia: A Plea for
      a Different Intensivist's Role.

PMID- 25978158
TI  - Colistin dosing without pharmacokinetic data: the relic of a bygone era.

PMID- 25978159
TI  - Combination Therapy for Extreme Drug-Resistant Acinetobacter baumannii: Ready for
      Prime Time?

PMID- 25978161
TI  - Systemic inflammatory response after cardiac arrest: potential target for
      therapy?

PMID- 25978160
TI  - Posttraumatic stress disorder symptoms among family decision makers and the
      potential relevance of study attrition.

PMID- 25978162
TI  - The "big" dilemma: ICU volume-outcome relationships.

PMID- 25978163
TI  - Homeless Patients in the ICU: An Observational Propensity-Matched Cohort Study.

PMID- 25978164
TI  - Functional outcomes after critical illness in the elderly.

PMID- 25978165
TI  - Electronic health record: what do you expect from them?

PMID- 25978166
TI  - Middle East respiratory syndrome: the need for better evidence in severe
      respiratory viral infections.

PMID- 25978167
TI  - Time for tailored antimicrobials: adapted bacteriophages in the ICU.

PMID- 25978168
TI  - Targeting sirtuin to modulate human inflammation.

PMID- 25978169
TI  - The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine
      Release and Coagulation Activation in Humans.
AB  - OBJECTIVES: Sirtuin 1 influences gene expression and other cellular functions
      through deacetylation of histone and nonhistone proteins. We here sought to
      determine the effects of a small molecule sirtuin 1 activator, SRT2104, on
      inflammation and coagulation induced by lipopolysaccharide in humans. DESIGN: A
      randomized, double-blind, placebo-controlled study. SETTING: An academic
      hospital. SUBJECTS: Twenty-four healthy humans. INTERVENTIONS: All subjects
      received an intravenous injection with lipopolysaccharide. Subjects were
      randomized to one of three groups (n=8 per group): 1) pretreatment with oral
      SRT2104 for 7 days (2 g/d), 2) pretreatment with a single SRT2104 dose (2 g), or
      3) placebo. MEASUREMENTS AND MAIN RESULTS: SRT2104 attenuated lipopolysaccharide
      induced release of the cytokines interleukin-6 (mean peak levels of 58.8%
      [p<0.05] and 80.9% [p=0.078] after single and repeated SRT2104 administration,
      respectively, relative to those measured after placebo treatment) and interleukin
      8 (mean peak levels of 57.0% [p<0.05 vs placebo] and 77.1% [p<0.05 vs placebo]
      after single and repeated SRT2104 ingestion, respectively, while not affecting
      tumor necrosis factor-alpha and interleukin-10 release). SRT2104 also reduced the
      lipopolysaccharide-induced acute phase protein response (C-reactive protein).
      SRT2104 inhibited activation of coagulation, as reflected by lower plasma levels
      of the prothrombin fragment F1+2 (mean peak levels 57.9% [p<0.05] and 64.2%
      [p<0.05] after single and repeated SRT2104 administration, respectively, relative
      to those measured after placebo treatment). Activation of the vascular
      endothelium (plasma von Willebrand levels) and the fibrinolytic system (plasma
      tissue-type plasminogen activator and plasminogen activator inhibitor type I) was
      not influenced by SRT2104. CONCLUSIONS: This is the first human study to
      demonstrate biological anti-inflammatory and anticoagulant responses consistent
      with the activation of sirtuin 1 by a small molecule.

PMID- 25978170
TI  - The brain is not dead when the cortex is dead.

PMID- 25978171
TI  - The authors reply.

PMID- 25978172
TI  - Serial blood lactate levels reflect both lactate production and clearance.

PMID- 25978173
TI  - The author replies.

PMID- 25978174
TI  - Prioritizing the intoxicated patients for extracorporeal treatments in methanol
      poisoning.

PMID- 25978175
TI  - The authors reply.

PMID- 25978176
TI  - What is the best heparin to treat sepsis with?

PMID- 25978177
TI  - The authors reply.

PMID- 25978178
TI  - New classification of acute respiratory distress syndrome: not so convincing.

PMID- 25978179
TI  - The authors reply.

PMID- 25978180
TI  - Oxygenation during high-flow nasal cannula in tracheal intubation: do we know the
      "red desaturation line"?

PMID- 25978181
TI  - The authors reply.

PMID- 25978182
TI  - Risk factors for anticoagulant thromboprophylaxis failure in critically ill
      patients.

PMID- 25978183
TI  - The need to facilitate unobstructed gasping during bystander cardiopulmonary
      resuscitation.

PMID- 25978184
TI  - Walking direction triggers visuo-spatial orienting in 6-month-old infants and
      adults: An eye tracking study.
AB  - The present study investigates whether the walking direction of a biological
      motion point-light display can trigger visuo-spatial attention in 6-month-old
      infants. A cueing paradigm and the recording of eye movements in a free viewing
      condition were employed. A control group of adults took part in the experiment.
      Participants were presented with a central point-light display depicting a
      walking human, followed by a single peripheral target. In experiment 1, the
      central biological motion stimulus depicting a walking human could be upright or
      upside-down and was facing either left or right. Results revealed that the
      latency of saccades toward the peripheral target was modulated by the congruency
      between the facing direction of the cue and the position of the target. In
      infants, as well as in adults, saccade latencies were shorter when the target
      appeared in the position signalled by the facing direction of the point-light
      walker (congruent trials) than when the target appeared in the contralateral
      position (incongruent trials). This cueing effect was present only when the
      biological motion cue was presented in the upright condition and not when the
      display was inverted. In experiment 2, a rolling point-light circle with
      unambiguous direction was adopted. Here, adults were influenced by the direction
      of the central cue. However no effect of congruency was found in infants. This
      result suggests that biological motion has a priority as a cue for spatial
      attention during development. 

PMID- 25978185
TI  - Expression of DMP1 in the developing mouse tongue embryo.
AB  - Dentin matrix protein 1 (DMP-1) is an important factor in the mineralization of
      hard tissues. However, it has many other functions in addition to the regulation
      of mineralized tissues. We analyzed the expression and localization of DMP-1 by
      immunohistochemical staining and in situ hybridization in the developing mouse
      tongue during embryonic days 12.5 (E12.5), E14.5, E17.5, and E18.5. We also
      detected the mRNA abundance of tongue morphogenesis markers such as FGF6, TGF
      beta1, Collagen I, osteocalcin, chondromodulin 1, tenomodulin, Vascular
      endothelial growth factor (VEGF), caspase-3, and Aifm from embryonic stages by
      real-time RT-PCR. The antisense probe for DMP-1 was detected in a few mesenchymal
      cells surrounding blood vessels at E12.5, and faint localization was seen at
      E18.5 in the embryonic mouse tongue by in situ hybridization. The DMP-1 and
      osteocalcin abundance levels gradually increased compared with the other tongue
      markers from E12.5 to E18.5 (p<0.001). Cluster analyses identified the following
      distinct clusters for mRNA abundance in the tongue: cluster 1, E12.5; cluster 2,
      E14.5 and E17.5; and cluster 3, E18.5. The positive correlation between DMP-1 and
      osteocalcin (Pearson's r=0.685; p<0.05) and negative correlation between DMP-1
      and Caspase-3 (Pearson's r=-0.632; p<0.05) were analyzed. These data suggested
      that DMP-1 potentially influences osteocalcin and Caspase-3 during mouse tongue
      development and morphogenesis. DMP-1 also affects the angiogenic marker VEGF in
      specific stages and areas, terminating the differentiation of the tongue from
      other developing tissues. We conclude that DMP-1 may be involved in regulating
      the temporal expression at embryonic stages in the mouse tongue.

PMID- 25978188
TI  - Adsorption of Cu(2+), Cd(2+) and Ni(2+) from aqueous single metal solutions on
      graphene oxide membranes.
AB  - Novel, highly ordered layered graphene oxide (GO) membranes with larger
      interlayer spacing were prepared by induced directional flow and were used as
      adsorbents for the removal of Cu(2+), Cd(2+) and Ni(2+) from aqueous solutions.
      The effects of pH, ionic strength, contact time, metal ion concentration and
      cycle time on Cu(2+), Cd(2+) and Ni(2+) sorption were investigated. The results
      indicated that the adsorption of Cu(2+), Cd(2+) and Ni(2+) onto GO membranes was
      greatly influenced by the pH and weakly affected by the ionic strength. The
      adsorption isotherms for Cu(2+), Cd(2+) and Ni(2+) were well fitted by the
      Langmuir model. The maximum adsorption capacities of the GO membranes for Cu(2+),
      Cd(2+) and Ni(2+) were approximately 72.6, 83.8 and 62.3 mg/g, respectively. The
      adsorption kinetics of Cu(2+), Cd(2+) and Ni(2+) onto GO membranes followed the
      pseudo-second-order model. The adsorption equilibrium was reached in a shorter
      time. The GO membranes can be regenerated more than six times based on their
      adsorption/desorption cycles, with a slight loss in the adsorption capacity. The
      results demonstrated that the GO membranes can be used as effective adsorbents
      for heavy metal removal from water.

PMID- 25978186
TI  - Isolation and Characterization of China Isolates of Duddingtonia flagrans, a
      Candidate of the Nematophagous Fungi for Biocontrol of Animal Parasitic
      Nematodes.
AB  - The nematophagous fungus Duddingtonia flagrans has been investigated as a
      biological agent for the control of gastrointestinal nematodes infecting domestic
      animals in other countries. However, D. flagrans has not been detected in China.
      In this study 1,135 samples were examined from 2012 to 2014; 4 D. flagrans
      isolates (SDH 035, SDH 091, SFH 089, SFG 170) were obtained from the feces of
      domestic animals and dung compost. The 4 isolates were then characterized
      morphologically. The SDH 035 strain was characterized by sequencing the ITS1-5.8S
      rDNA-ITS2 region. A BLAST search showed that the SDH 035 strain (GenBank
      KP257593) was 100% identical to Arthrobotrys flagrans (AF106520) and was
      identified as D. flagrans. The morphological plasticity of the isolated strain
      and the interaction of this strain with the nematode targets were observed by
      subjecting the infected trichostrongylide L3 to scanning electron microscopy. At
      6 and 8 hr after trichostrongylide L(3) was added, hyphal ramifications were
      observed and L(3) were captured, respectively. Scanning electron micrographs were
      obtained at 0, 6, 12, 18, 24, 30, 36, 42, and 48 hr, where 0 is the time when
      trichostrongylide L(3) were first captured by the fungus. The details of the
      capture process by the fungus are also described. Chlamydospores were observed in
      the body of L(3) in the late stage of digestion. A sticky substance and bacteria
      could be observed in contact areas between predation structures and nematode
      cuticle.

PMID- 25978189
TI  - Comparative study on the reactivity of Fe/Cu bimetallic particles and zero valent
      iron (ZVI) under different conditions of N2, air or without aeration.
AB  - In order to further compare the degradation capacity of Fe(0) and Fe/Cu
      bimetallic system under different aeration conditions, the mineralization of PNP
      under different aeration conditions has been investigated thoroughly. The results
      show that the removal of PNP by Fe(0) or Fe/Cu system followed the pseudo-first
      order reaction kinetics. Under the optimal conditions, the COD removal
      efficiencies obtained through Fe(0) or Fe/Cu system under different aeration
      conditions followed the trend that Fe/Cu (air)>Fe/Cu (N2: 0-30 min, air: 30-120
      min)>control-Fe (air)>Fe/Cu (without aeration)>Fe/Cu (N2)>control-Fe (N2). It
      revealed that dissolved oxygen (DO) could improve the mineralization of PNP, and
      Cu could enhance the reactivity of Fe(0). In addition, the degradation of PNP was
      further analyzed by using UV-vis, FTIR and GC/MS, and the results suggest that
      Fe/Cu bimetallic system with air aeration could completely break the benzene ring
      and NO2 structure of PNP and could generate the nontoxic and biodegradable
      intermediate products. Meanwhile, most of these intermediate products were
      further mineralized into CO2 and H2O, which brought about a high COD removal
      efficiency (83.8%). Therefore, Fe/Cu bimetallic system with air aeration would be
      a promising process for toxic refractory industry wastewater.

PMID- 25978191
TI  - PROSPECTIVE ASSOCIATIONS OF DEPRESSIVE RUMINATION AND SOCIAL PROBLEM SOLVING WITH
      DEPRESSION: A 6-MONTH LONGITUDINAL STUDY(.).
AB  - The main purpose of this study was to examine whether depressive rumination and
      social problem solving are prospectively associated with depressive symptoms.
      Nonclinical university students (N = 161, 64 men, 97 women; M age = 19.7 yr., SD
      = 3.6, range = 18-61) recruited from three universities in Japan completed the
      Beck Depression Inventory-Second Edition (BDI-II), the Ruminative Responses
      Scale, Social Problem-Solving Inventory-Revised Short Version (SPSI-R:S), and the
      Means-Ends Problem-Solving Procedure at baseline, and the BDI-II again at 6 mo.
      later. A stepwise multiple regression analysis with the BDI-II and all subscales
      of the rumination and social problem solving measures as independent variables
      indicated that only the BDI-II scores and the Impulsivity/carelessness style
      subscale of the SPSI-R:S at Time 1 were significantly associated with BDI-II
      scores at Time 2 (beta = 0.73, 0.12, respectively; independent variables
      accounted for 58.8% of the variance). These findings suggest that in Japan an
      impulsive and careless problem-solving style was prospectively associated with
      depressive symptomatology 6 mo. later, as contrasted with previous findings of a
      cycle of rumination and avoidance problem-solving style.

PMID- 25978190
TI  - A combination of electro-enzymatic catalysis and electrocoagulation for the
      removal of endocrine disrupting chemicals from water.
AB  - We in this study investigated a novel electrochemical approach combining electro
      enzyme and electrocoagulation to precipitate bisphenol A (BPA) from water
      containing humic acid (HA). Horseradish peroxidase was immobilized on the
      graphite felt of Ti electrode as HRP-GF/Ti cathode, with aluminum plate anode
      establishing a pair of working electrodes. BPA was 100% removed and the reduction
      of total organic carbon (TOC) reached 95.1% after 20-min sequencing treatment
      with the current density of 2.3 mA/cm(2). Real wastewater (TOC=28.76 mg/L,
      BPA=4.1 MUg/L) also can achieve 94% BPA removal and 52% TOC reduction after
      sequencing treatment. Additionally, coupled electro-system with continuous flow
      only required energy of 0.016 kWh/m(3) to achieve simultaneous 90% BPA and 85%
      TOC removal. As indicated in the time-of-flight mass spectrometry and FTIR
      spectra, the electro-enzymatic process not only oxidized BPA into dimer and BPA
      3,4-quinone, but also greatly altered the chemical and structural features of HA,
      where hydrophilic moieties (phenolic and alcohols) transformed into hydrophobic
      forms (ethers, quinone and aliphatic). These polymerized products were
      effectively separated from aquous solution during anodic electrocoagulation,
      leading to significant removal of BPA and TOC. Thus, the coupled process may
      provide a faster and less energy strategy to control certain emerging
      contaminants in water/wastewater treatment.

PMID- 25978192
TI  - Iridium-based complexes for water oxidation.
AB  - Organometallic Ir precatalysts have been found to yield homogeneous Ir-based
      water-oxidation catalysts (WOCs) with very high activity. The Cp*Ir catalyst
      series can operate under a variety of regimes: it can either act as a homogeneous
      or a heterogeneous catalyst; it can be driven by chemical, photochemical, or
      electrochemical methods; and the molecular catalyst can either act in solution or
      supported as a molecular unit on a variety of solid oxides. In addition to
      optimizing the various reaction conditions, work has continued to elucidate the
      catalyst activation mechanism and identify water-oxidation intermediates. This
      Perspective will describe the development of the Cp*Ir series, their many forms
      as WOCs, and their ongoing characterization. 

PMID- 25978194
TI  - Corrections.

PMID- 25978193
TI  - Physicians must be vigilant for sex trafficking in unaccompanied minors.

PMID- 25978196
TI  - USPSTF Recommendations That Were New or Updated in 2014.

PMID- 25978197
TI  - Sore throat.

PMID- 25978198
TI  - Common questions about the management of gastroesophageal reflux disease.
AB  - Common questions that arise regarding treatment of gastroesophageal reflux
      disease (GERD) include which medications are most effective, when surgery may be
      indicated, which patients should be screened for Barrett esophagus and
      Helicobacter pylori infection, and which adverse effects occur with these
      medications. Proton pump inhibitors (PPIs) are the most effective medical
      therapy, and all PPIs provide similar relief of GERD symptoms. There is
      insufficient evidence to recommend testing for H. pylori in patients with GERD.
      In the absence of alarm symptoms, endoscopy is not necessary to make an initial
      diagnosis of GERD. Patients with alarm symptoms require endoscopy. Screening for
      Barrett esophagus is not routinely recommended, but may be considered in white
      men 50 years or older who have had GERD symptoms for at least five years. Symptom
      remission rates in patients with chronic GERD are similar in those who undergo
      surgery vs. medical management. PPI therapy has been associated with an increased
      risk of hip fracture, hypomagnesemia, community-acquired pneumonia, vitamin B12
      deficiency, and Clostridium difficile infection. 

PMID- 25978199
TI  - Evaluation of neck masses in adults.
AB  - Neck masses are often seen in clinical practice, and the family physician should
      be able to determine the etiology of a mass using organized, efficient diagnostic
      methods. The first goal is to determine if the mass is malignant or benign;
      malignancies are more common in adult smokers older than 40 years. Etiologies can
      be grouped according to whether the onset/duration is acute (e.g., infectious),
      subacute (e.g., squamous cell carcinoma), or chronic (e.g., thyroid), and further
      narrowed by patient demographics. If the history and physical examination do not
      find an obvious cause, imaging and surgical tools are helpful. Contrast-enhanced
      computed tomography is the initial diagnostic test of choice in adults. Computed
      tomography angiography is recommended over magnetic resonance angiography for the
      evaluation of pulsatile neck masses. If imaging rules out involvement of
      underlying vital structures, a fine-needle aspiration biopsy can be performed,
      providing diagnostic information via cytology, Gram stain, and bacterial and acid
      fast bacilli cultures. The sensitivity and specificity of fine-needle aspiration
      biopsy in detecting a malignancy range from 77% to 97% and 93% to 100%,
      respectively. 

PMID- 25978201
TI  - Losing weight and motivating others.

PMID- 25978200
TI  - Common questions about chronic low back pain.
AB  - More than 30% of U.S. adults report having experienced low back pain within the
      preceding three months. Although most low back pain is nonspecific and self
      limiting, a subset of patients develop chronic low back pain, defined as
      persistent symptoms for longer than three months. Low back pain is categorized as
      nonspecific low back pain without radiculopathy, low back pain with radicular
      symptoms, or secondary low back pain with a spinal cause. Imaging should be
      reserved for patients with red flags for cauda equina syndrome, recent trauma,
      risk of infection, or when warranted before treatment (e.g., surgical,
      interventional). Prompt recognition of cauda equina syndrome is critical. Patient
      education should be combined with evidence-guided pharmacologic therapy. Goals of
      therapy include reducing the severity of pain symptoms, pain interference, and
      disability, as well as maximizing activity. Validated tools such as the Oswestry
      Disability Index can help assess symptom severity and functional change in
      patients with chronic low back pain. Epidural steroid injections do not improve
      pain or disability in patients with spinal stenosis. Spinal manipulation therapy
      produces small benefits for up to six months. Because long-term data are lacking
      for spinal surgery, patient education about realistic outcome expectations is
      essential. 

PMID- 25978202
TI  - Screening for carotid artery stenosis.

PMID- 25978204
TI  - Acute onset of polyarthralgia and skin plaques.

PMID- 25978205
TI  - If it seems too good to be true...

PMID- 25978207
TI  - Screening for asymptomatic carotid artery stenosis: recommendation statement.

PMID- 25978209
TI  - Does A1c Have to Change for Hypoglycemia Reduction?

PMID- 25978211
TI  - Two-time correlations probing the dynamics of dissipative many-body quantum
      systems: aging and fast relaxation.
AB  - We use two-time correlation functions to study the complex dynamics of
      dissipative many-body quantum systems. In order to measure, understand, and
      categorize these correlations we extend the framework of the adiabatic
      elimination method. We show that, for the same parameters and times, two-time
      correlations can display two distinct behaviors depending on the observable
      considered: a fast exponential decay or a much slower dynamics. We exemplify
      these findings by studying strongly interacting bosons in a double well subjected
      to phase noise. While the single-particle correlations decay exponentially fast
      with time, the density-density correlations display slow aging dynamics. We also
      show that this slow relaxation regime is robust against particle losses.
      Additionally, we use the developed framework to show that the dynamic properties
      of dissipatively engineered states can be drastically different from their
      Hamiltonian counterparts. 

PMID- 25978212
TI  - Quantum brachistochrone curves as geodesics: obtaining accurate minimum-time
      protocols for the control of quantum systems.
AB  - Most methods of optimal control cannot obtain accurate time-optimal protocols.
      The quantum brachistochrone equation is an exception, and has the potential to
      provide accurate time-optimal protocols for a wide range of quantum control
      problems. So far, this potential has not been realized, however, due to the
      inadequacy of conventional numerical methods to solve it. Here we show that the
      quantum brachistochrone problem can be recast as that of finding geodesic paths
      in the space of unitary operators. We expect this brachistochrone-geodesic
      connection to have broad applications, as it opens up minimal-time control to the
      tools of geometry. As one such application, we use it to obtain a fast numerical
      method to solve the brachistochrone problem, and apply this method to two
      examples demonstrating its power. 

PMID- 25978213
TI  - Quantum Random Access Codes Using Single d-Level Systems.
AB  - Random access codes (RACs) are used by a party to, with limited communication,
      access an arbitrary subset of information held by another party. Quantum
      resources are known to enable RACs that break classical limitations. Here, we
      study quantum and classical RACs with high-level communication. We derive average
      performances of classical RACs and present families of high-level quantum RACs.
      Our results show that high-level quantum systems can significantly increase the
      advantage of quantum RACs over their classical counterparts. We demonstrate our
      findings in an experimental realization of a quantum RAC with four-level
      communication. 

PMID- 25978214
TI  - Coherent storage of microwave excitations in rare-earth nuclear spins.
AB  - Interfacing between various elements of a computer--from memory to processors to
      long range communication--will be as critical for quantum computers as it is for
      classical computers today. Paramagnetic rare-earth doped crystals, such as
      Nd(3+):Y2SiO5(YSO), are excellent candidates for such a quantum interface: they
      are known to exhibit long optical coherence lifetimes (for communication via
      optical photons), possess a nuclear spin (memory), and have in addition an
      electron spin that can offer hybrid coupling with superconducting qubits
      (processing). Here we study two of these three elements, demonstrating coherent
      storage and retrieval between electron and (145)Nd nuclear spin states in
      Nd(3+):YSO. We find nuclear spin coherence times can reach 9 ms at ~5  K, about 2
      orders of magnitude longer than the electron spin coherence, while quantum state
      and process tomography of the storage or retrieval operation between the electron
      and nuclear spin reveal an average state fidelity of 0.86. The times and
      fidelities are expected to further improve at lower temperatures and with more
      homogeneous radio-frequency excitation.

PMID- 25978215
TI  - Revealing genuine optical-path entanglement.
AB  - How can one detect entanglement between multiple optical paths sharing a single
      photon? We address this question by proposing a scalable protocol, which only
      uses local measurements where single photon detection is combined with small
      displacement operations. The resulting entanglement witness does not require
      postselection, nor assumptions about the photon number in each path. Furthermore,
      it guarantees that entanglement lies in a subspace with at most one photon per
      optical path and reveals genuinely multipartite entanglement. We demonstrate its
      scalability and resistance to loss by performing various experiments with two and
      three optical paths. We anticipate applications of our results for quantum
      network certification. 

PMID- 25978216
TI  - Many-Body Localization Implies that Eigenvectors are Matrix-Product States.
AB  - The phenomenon of many-body localization has received a lot of attention
      recently, both for its implications in condensed-matter physics of allowing
      systems to be an insulator even at nonzero temperature as well as in the context
      of the foundations of quantum statistical mechanics, providing examples of
      systems showing the absence of thermalization following out-of-equilibrium
      dynamics. In this work, we establish a novel link between dynamical properties--a
      vanishing group velocity and the absence of transport--with entanglement
      properties of individual eigenvectors. For systems with a generic spectrum, we
      prove that strong dynamical localization implies that all of its many-body
      eigenvectors have clustering correlations. The same is true for parts of the
      spectrum, thus allowing for the existence of a mobility edge above which
      transport is possible. In one dimension these results directly imply an
      entanglement area law; hence, the eigenvectors can be efficiently approximated by
      matrix-product states.

PMID- 25978217
TI  - Entropic Description of Gas Hydrate Ice-Liquid Equilibrium via Enhanced Sampling
      of Coexisting Phases.
AB  - Metastable beta ice holds small guest molecules in stable gas hydrates, so its
      solid-liquid equilibrium is of interest. However, aqueous crystal-liquid
      transitions are very difficult to simulate. A new molecular dynamics algorithm
      generates trajectories in a generalized NPT ensemble and equilibrates states of
      coexisting phases with a selectable enthalpy. With replicas spanning the range
      between beta ice and liquid water, we find the statistical temperature from the
      enthalpy histograms and characterize the transition by the entropy, introducing a
      general computational procedure for first-order transitions. 

PMID- 25978218
TI  - Power-recycled weak-value-based metrology.
AB  - We improve the precision of the interferometric weak-value-based beam deflection
      measurement by introducing a power recycling mirror, creating a resonant cavity.
      This results in all the light exiting to the detector with a large deflection,
      thus eliminating the inefficiency of the rare postselection. The signal-to-noise
      ratio of the deflection is itself magnified by the weak value. We discuss ways to
      realize this proposal, using a transverse beam filter and different cavity
      designs. 

PMID- 25978219
TI  - Linear optical quantum metrology with single photons: exploiting spontaneously
      generated entanglement to beat the shot-noise limit.
AB  - Quantum number-path entanglement is a resource for supersensitive quantum
      metrology and in particular provides for sub-shot-noise or even Heisenberg
      limited sensitivity. However, such number-path entanglement has been thought to
      be resource intensive to create in the first place--typically requiring either
      very strong nonlinearities, or nondeterministic preparation schemes with
      feedforward, which are difficult to implement. Very recently, arising from the
      study of quantum random walks with multiphoton walkers, as well as the study of
      the computational complexity of passive linear optical interferometers fed with
      single-photon inputs, it has been shown that such passive linear optical devices
      generate a superexponentially large amount of number-path entanglement. A logical
      question to ask is whether this entanglement may be exploited for quantum
      metrology. We answer that question here in the affirmative by showing that a
      simple, passive, linear-optical interferometer--fed with only uncorrelated,
      single-photon inputs, coupled with simple, single-mode, disjoint photodetection-
      is capable of significantly beating the shot-noise limit. Our result implies a
      pathway forward to practical quantum metrology with readily available technology.

PMID- 25978220
TI  - What is the Flavor of the Cosmic Neutrinos Seen by IceCube?
AB  - We analyze the high-energy neutrino events observed by IceCube, aiming to probe
      the initial flavor of cosmic neutrinos. We study the track-to-shower ratio of the
      subset with energy above 60 TeV, where the signal is expected to dominate, and
      show that different production mechanisms give rise to different predictions even
      accounting for the uncertainties due to neutrino oscillations. We include for the
      first time the passing muons observed by IceCube in the analysis. They
      corroborate the hypotheses that cosmic neutrinos have been seen and their flavor
      matches expectations derived from the neutrino oscillations. 

PMID- 25978223
TI  - Spinodal instabilities and super-Planckian excursions in natural inflation.
AB  - Models such as Natural Inflation that use pseudo-Nambu-Goldstone bosons as the
      inflaton are attractive for many reasons. However, they typically require trans
      Planckian field excursions DeltaPhi>MPl, due to the need for an axion decay
      constant f>MPl to have both a sufficient number of e-folds and values of ns,r
      consistent with data. Such excursions would in general require the addition of
      all other higher dimension operators consistent with symmetries, thus disrupting
      the required flatness of the potential and rendering the theory nonpredictive. We
      show that in the case of Natural Inflation, the existence of spinodal
      instabilities (modes with tachyonic masses) can modify the inflaton equations of
      motion to the point that versions of the model with f<MPl can still inflate for
      the required number of e-folds. The instabilities naturally give rise to two
      separate phases of inflation with different values of the Hubble parameter H, one
      driven by the zero mode, the other by the unstable fluctuation modes. The values
      of ns and r typically depend on the initial conditions for the zero mode, and, at
      least for those examined here, the values of r tend to be unobservably small.

PMID- 25978224
TI  - Black holes in higher derivative gravity.
AB  - Extensions of Einstein gravity with higher-order derivative terms arise in string
      theory and other effective theories, as well as being of interest in their own
      right. In this Letter we study static black-hole solutions in the example of
      Einstein gravity with additional quadratic curvature terms. A Lichnerowicz-type
      theorem simplifies the analysis by establishing that they must have vanishing
      Ricci scalar curvature. By numerical methods we then demonstrate the existence of
      further black-hole solutions over and above the Schwarzschild solution. We
      discuss some of their thermodynamic properties, and show that they obey the first
      law of thermodynamics. 

PMID- 25978226
TI  - Loophole in K->pinunu Search and New Weak Leptonic Forces.
AB  - Weakly interacting K->piX(0) emission with mX(0)?mpi(0) is out of sight of the
      current K+->pi+ nunu study, but it can be sensed by the KL->pi(0)nunu search.
      This evades the usual Grossman-Nir bound of B(KL->pi(0)nunu)<1.4*10(-9); thus,
      the KOTO experiment is already starting to probe new physics. An intriguing
      possibility is the Z' gauge boson of a weak leptonic force that couples to LMU
      Ltau (the difference between the muon and tauon numbers), which may explain the
      long-standing "muon g-2" anomaly, but is constrained by nuMUN->nuMUNMU+ MU-
      scattering to mZ'?400  MeV. An explicit model for K->piZ' is given, which
      illustrates the link between rare kaon and B->KMU+ MU-, K(*)nunu decays.
      Complementary to these searches and future lepton experiments, the LHC might
      discover the scalar boson phi responsible for light mZ' generation via phi->Z'Z'
      >2(MU+ MU-).

PMID- 25978227
TI  - Selective production of Rydberg-stark states of positronium.
AB  - Rydberg positronium (Ps) atoms have been prepared in selected Stark states via
      two-step (1s->2p->nd/ns) optical excitation. Two methods have been used to
      achieve Stark-state selection: a field ionization filter that transmits the
      outermost states with positive Stark shifts, and state-selected photoexcitation
      in a strong electric field. The former is demonstrated for n=17 and 18 while the
      latter is performed for n=11 in a homogeneous electric field of 1.9  kV/cm. The
      observed spectral intensities and their dependence on the polarization of the
      laser radiation are in agreement with calculations that include the perturbations
      of the intermediate n=2 manifold. Our results pave the way for the generation of
      Rydberg Ps atoms with large electric dipole moments that are required for the
      realization of schemes to control their motion using inhomogeneous electric
      fields, an essential feature of some proposed Ps free-fall measurements requiring
      focused beams of long-lived atoms. 

PMID- 25978228
TI  - Designing frustrated quantum magnets with laser-dressed Rydberg atoms.
AB  - We show how a broad class of lattice spin-1/2 models with angular- and distance
      dependent couplings can be realized with cold alkali atoms stored in optical or
      magnetic trap arrays. The effective spin-1/2 is represented by a pair of atomic
      ground states, and spin-spin interactions are obtained by admixing van der Waals
      interactions between fine-structure split Rydberg states with laser light. The
      strengths of the diagonal spin interactions as well as the "flip-flop," and "flip
      flip" and "flop-flop" interactions can be tuned by exploiting quantum
      interference, thus realizing different spin symmetries. The resulting energy
      scales of interactions compare well with typical temperatures and decoherence
      time scales, making the exploration of exotic forms of quantum magnetism,
      including emergent gauge theories and compass models, accessible within state-of
      the-art experiments. 

PMID- 25978229
TI  - Two-dimensional attosecond electron wave-packet interferometry.
AB  - We propose a two-dimensional interferometry based on the electron wave-packet
      interference by using a cycle-shaped orthogonally polarized two-color laser
      field. With such a method, the subcycle and intercycle interferences can be
      disentangled into different directions in the measured photoelectron momentum
      spectra. The Coulomb influence can be minimized and the overlapping of
      interference fringes with the complicated low-energy structures can be avoided as
      well. The contributions of the excitation effect and the long-range Coulomb
      potential can be traced in the Fourier domain of the photoelectron distribution.
      Because of these advantages, precise information on valence electron dynamics of
      atoms or molecules with attosecond temporal resolution and additional spatial
      information with angstrom resolution can be obtained with the two-dimensional
      electron wave-packet interferometry. 

PMID- 25978230
TI  - Frequency-dependent polarizability of helium including relativistic effects with
      nuclear recoil terms.
AB  - Future metrology standards will be partly based on physical quantities computed
      from first principles rather than measured. In particular, a new pressure
      standard can be established if the dynamic polarizability of helium can be
      determined from theory with an uncertainty smaller than 0.2 ppm. We present
      calculations of the frequency-dependent part of this quantity including
      relativistic effects with full account of leading nuclear recoil terms and using
      highly optimized explicitly correlated basis sets. A particular emphasis is put
      on uncertainty estimates. At the He-Ne laser wavelength of 632.9908 nm, the
      computed polarizability value of 1.39181141 a.u. has uncertainty of 0.1 ppm that
      is 2 orders of magnitude smaller than those of the most accurate polarizability
      measurements. We also obtained an accurate expansion of the helium refractive
      index in powers of density. 

PMID- 25978231
TI  - Time-reversal-symmetric single-photon wave packets for free-space quantum
      communication.
AB  - Readout and retrieval processes are proposed for efficient, high-fidelity quantum
      state transfer between a matter qubit, encoded in the level structure of a single
      atom or ion, and a photonic qubit, encoded in a time-reversal-symmetric single
      photon wave packet. They are based on controlling spontaneous photon emission and
      absorption of a matter qubit on demand in free space by stimulated Raman
      adiabatic passage. As these processes do not involve mode selection by high
      finesse cavities or photon transport through optical fibers, they offer
      interesting perspectives as basic building blocks for free-space quantum
      communication protocols. 

PMID- 25978232
TI  - Quantum state engineering with circuit electromechanical three-body interactions.
AB  - We propose a hybrid system with quantum mechanical three-body interactions
      between photons, phonons, and qubit excitations. These interactions take place in
      a circuit quantum electrodynamical architecture with a superconducting microwave
      resonator coupled to a transmon qubit whose shunt capacitance is free to
      mechanically oscillate. We show that this system design features a three-mode
      polariton-mechanical mode and a nonlinear transmon-mechanical mode interaction in
      the strong coupling regime. Together with the strong resonator-transmon
      interaction, these properties provide intriguing opportunities for manipulations
      of this hybrid quantum system. We show, in particular, the feasibility of cooling
      the mechanical motion down to its ground state and preparing various nonclassical
      states including mechanical Fock and cat states and hybrid tripartite entangled
      states. 

PMID- 25978233
TI  - Photon sorting, efficient bell measurements, and a deterministic controlled-Z
      gate using a passive two-level nonlinearity.
AB  - Although the strengths of optical nonlinearities available experimentally have
      been rapidly increasing in recent years, significant challenges remain to using
      such nonlinearities to produce useful quantum devices such as efficient optical
      Bell state analyzers or universal quantum optical gates. Here we describe a new
      approach that avoids the current limitations by combining strong nonlinearities
      with active Gaussian operations in efficient protocols for Bell state analyzers
      and controlled-sign gates. 

PMID- 25978234
TI  - Generation of intense high-order vortex harmonics.
AB  - This Letter presents for the first time a scheme to generate intense high-order
      optical vortices that carry orbital angular momentum in the extreme ultraviolet
      region based on relativistic harmonics from the surface of a solid target. In the
      three-dimensional particle-in-cell simulation, the high-order harmonics of the
      high-order vortex mode is generated in both reflected and transmitted light beams
      when a linearly polarized Laguerre-Gaussian laser pulse impinges on a solid foil.
      The azimuthal mode of the harmonics scales with its order. The intensity of the
      high-order vortex harmonics is close to the relativistic region, with the pulse
      duration down to attosecond scale. The obtained intense vortex beam possesses the
      combined properties of fine transversal structure due to the high-order mode and
      the fine longitudinal structure due to the short wavelength of the high-order
      harmonics. In addition to the application in high-resolution detection in both
      spatial and temporal scales, it also presents new opportunities in the intense
      vortex required fields, such as the inner shell ionization process and high
      energy twisted photons generation by Thomson scattering of such an intense vortex
      beam off relativistic electrons. 

PMID- 25978235
TI  - Topological properties of linear circuit lattices.
AB  - Motivated by the topologically insulating circuit of capacitors and inductors
      proposed and tested by Jia et al. [arXiv:1309.0878], we present a related circuit
      with fewer elements per site. The normal mode frequency matrix of our circuit is
      unitarily equivalent to the hopping matrix of a quantum spin Hall insulator, and
      we identify perturbations that do not backscatter the circuit's edge modes. The
      idea behind these models is generalized, providing a platform to simulate tunable
      and locally accessible lattices with arbitrary complex spin-dependent hopping of
      any range. A simulation of a non-Abelian Aharonov-Bohm effect using such linear
      circuit designs is discussed. 

PMID- 25978236
TI  - Quantum threshold for optomechanical self-structuring in a Bose-Einstein
      condensate.
AB  - Theoretical analysis of the optomechanics of degenerate bosonic atoms with a
      single feedback mirror shows that self-structuring occurs only above an input
      threshold that is quantum mechanical in origin. This threshold also implies a
      lower limit to the size (period) of patterns that can be produced in a condensate
      for a given pump intensity. These thresholds are interpreted as due to the
      quantum rigidity of Bose-Einstein condensates, which has no classical
      counterpart. Above the threshold, the condensate self-organizes into an ordered
      supersolid state with a spatial period self-selected by optical diffraction. 

PMID- 25978221
TI  - Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube.
AB  - A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the
      IceCube Neutrino Observatory. Here we extend this analysis to probe the
      astrophysical flux down to 35 TeV and analyze its flavor composition by
      classifying events as showers or tracks. Taking advantage of lower atmospheric
      backgrounds for showerlike events, we obtain a shower-biased sample containing
      129 showers and 8 tracks collected in three years from 2010 to 2013. We
      demonstrate consistency with the (fe:fMU:ftau)?~(1:1:1)? flavor ratio at Earth
      commonly expected from the averaged oscillations of neutrinos produced by pion
      decay in distant astrophysical sources. Limits are placed on nonstandard flavor
      compositions that cannot be produced by averaged neutrino oscillations but could
      arise in exotic physics scenarios. A maximally tracklike composition of (0:1:0)?
      is excluded at 3.3sigma, and a purely showerlike composition of (1:0:0)? is
      excluded at 2.3sigma.

PMID- 25978237
TI  - Attenuation of the dynamic yield point of shocked aluminum using elastodynamic
      simulations of dislocation dynamics.
AB  - When a metal is subjected to extremely rapid compression, a shock wave is
      launched that generates dislocations as it propagates. The shock wave evolves
      into a characteristic two-wave structure, with an elastic wave preceding a
      plastic front. It has been known for more than six decades that the amplitude of
      the elastic wave decays the farther it travels into the metal: this is known as
      "the decay of the elastic precursor." The amplitude of the elastic precursor is a
      dynamic yield point because it marks the transition from elastic to plastic
      behavior. In this Letter we provide a full explanation of this attenuation using
      the first method of dislocation dynamics to treat the time dependence of the
      elastic fields of dislocations explicitly. We show that the decay of the elastic
      precursor is a result of the interference of the elastic shock wave with elastic
      waves emanating from dislocations nucleated in the shock front. Our simulations
      reproduce quantitatively recent experiments on the decay of the elastic precursor
      in aluminum and its dependence on strain rate. 

PMID- 25978222
TI  - Precision Measurement of the Proton Flux in Primary Cosmic Rays from Rigidity 1
      GV to 1.8 TV with the Alpha Magnetic Spectrometer on the International Space
      Station.
AB  - A precise measurement of the proton flux in primary cosmic rays with rigidity
      (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events.
      Knowledge of the rigidity dependence of the proton flux is important in
      understanding the origin, acceleration, and propagation of cosmic rays. We
      present the detailed variation with rigidity of the flux spectral index for the
      first time. The spectral index progressively hardens at high rigidities. 

PMID- 25978238
TI  - Liquid ropes: a geometrical model for thin viscous jet instabilities.
AB  - Thin, viscous fluid threads falling onto a moving belt behave in a way
      reminiscent of a sewing machine, generating a rich variety of periodic stitchlike
      patterns including meanders, W patterns, alternating loops, and translated
      coiling. These patterns form to accommodate the difference between the belt speed
      and the terminal velocity at which the falling thread strikes the belt. Using
      direct numerical simulations, we show that inertia is not required to produce the
      aforementioned patterns. We introduce a quasistatic geometrical model which
      captures the patterns, consisting of three coupled ordinary differential
      equations for the radial deflection, the orientation, and the curvature of the
      path of the thread's contact point with the belt. The geometrical model
      reproduces well the observed patterns and the order in which they appear as a
      function of the belt speed. 

PMID- 25978239
TI  - Entropic lattice boltzmann method for multiphase flows.
AB  - A novel thermodynamically consistent lattice Boltzmann model that enables
      dynamical effects of two-phase fluids is developed. The key innovation is the
      application of the entropic lattice Boltzmann stabilization mechanism to control
      the dynamics at the liquid-vapor interface. This allows us to present a number of
      simulations of colliding droplets, including complex phenomena such as the
      formation of a stable lamella film. Excellent agreement of the simulation with
      recent experiments demonstrates the viability of the present approach to
      simulation of complex dynamic phenomena of multiphase fluids. 

PMID- 25978241
TI  - Intermittent Dissipation and Heating in 3D Kinetic Plasma Turbulence.
AB  - High resolution, fully kinetic, three dimensional (3D) simulation of
      collisionless plasma turbulence shows the development of turbulence characterized
      by sheetlike current density structures spanning a range of scales. The nonlinear
      evolution is initialized with a long wavelength isotropic spectrum of
      fluctuations having polarizations transverse to an imposed mean magnetic field.
      We present evidence that these current sheet structures are sites for heating and
      dissipation, and that stronger currents signify higher dissipation rates. The
      analyses focus on quantities such as J.E, electron, and proton temperatures, and
      conditional averages of these quantities based on local electric current density.
      Evidently, kinetic scale plasma, like magnetohydrodynamics, becomes intermittent
      due to current sheet formation, leading to the expectation that heating and
      dissipation in astrophysical and space plasmas may be highly nonuniform.
      Comparison with previous results from 2D kinetic simulations, as well as high
      frequency solar wind observational data, are discussed. 

PMID- 25978240
TI  - First high-convergence cryogenic implosion in a near-vacuum hohlraum.
AB  - Recent experiments on the National Ignition Facility [M. J. Edwards et al., Phys.
      Plasmas 20, 070501 (2013)] demonstrate that utilizing a near-vacuum hohlraum (low
      pressure gas-filled) is a viable option for high convergence cryogenic deuterium
      tritium (DT) layered capsule implosions. This is made possible by using a dense
      ablator (high-density carbon), which shortens the drive duration needed to
      achieve high convergence: a measured 40% higher hohlraum efficiency than typical
      gas-filled hohlraums, which requires less laser energy going into the hohlraum,
      and an observed better symmetry control than anticipated by standard
      hydrodynamics simulations. The first series of near-vacuum hohlraum experiments
      culminated in a 6.8 ns, 1.2 MJ laser pulse driving a 2-shock, high adiabat
      (alpha~3.5) cryogenic DT layered high density carbon capsule. This resulted in
      one of the best performances so far on the NIF relative to laser energy, with a
      measured primary neutron yield of 1.8*10(15) neutrons, with 20% calculated alpha
      heating at convergence ~27*.

PMID- 25978242
TI  - Crack front dynamics: the interplay of singular geometry and crack instabilities.
AB  - When fast cracks become unstable to microscopic branching (microbranching),
      fracture no longer occurs in an effective 2D medium. We follow in-plane crack
      front dynamics via real-time measurements in brittle gels as microbranching
      unfolds and progresses. We first show that spatially local energy balance
      quantitatively describes crack dynamics, even when translational invariance is
      badly broken. Furthermore, our results explain microbranch dynamics; why
      microbranches form along spatially localized chains and how finite-time formation
      of cusps along the crack front leads to their death. 

PMID- 25978225
TI  - Search for Long-Lived Particles in e+ e- Collisions.
AB  - We present a search for a neutral, long-lived particle L that is produced in e+ e
      collisions and decays at a significant distance from the e+ e- interaction point
      into various flavor combinations of two oppositely charged tracks. The analysis
      uses an e+ e- data sample with a luminosity of 489.1  fb(-1) collected by the
      BABAR detector at the Upsilon(4S), Upsilon(3S), and Upsilon(2S) resonances and
      just below the Upsilon(4S). Fitting the two-track mass distribution in search of
      a signal peak, we do not observe a significant signal, and set 90% confidence
      level upper limits on the product of the L production cross section, branching
      fraction, and reconstruction efficiency for six possible two-body L decay modes
      as a function of the L mass. The efficiency is given for each final state as a
      function of the mass, lifetime, and transverse momentum of the candidate,
      allowing application of the upper limits to any production model. In addition,
      upper limits are provided on the branching fraction B(B->XsL), where Xs is a
      strange hadronic system.

PMID- 25978244
TI  - Temperature-induced spontaneous time-reversal symmetry breaking on the honeycomb
      lattice.
AB  - Phase transitions involving spontaneous time-reversal symmetry breaking are
      studied on the honeycomb lattice at finite hole doping with next-nearest-neighbor
      repulsion. We derive an exact expression for the mean-field equation of state in
      closed form, valid at temperatures much less than the Fermi energy. Contrary to
      standard expectations, we find that thermally induced intraband particle-hole
      excitations can create and stabilize a uniform metallic phase with broken time
      reversal symmetry as the temperature is raised in a region where the ground state
      is a trivial metal. 

PMID- 25978243
TI  - Computation of the correlated metal-insulator transition in vanadium dioxide from
      first principles.
AB  - Vanadium dioxide (VO2) is a paradigmatic example of a strongly correlated system
      that undergoes a metal-insulator transition at a structural phase transition. To
      date, this transition has necessitated significant post hoc adjustments to theory
      in order to be described properly. Here we report standard state-of-the-art first
      principles quantum Monte Carlo (QMC) calculations of the structural dependence of
      the properties of VO2. Using this technique, we simulate the interactions between
      electrons explicitly, which allows for the metal-insulator transition to
      naturally emerge, importantly without ad hoc adjustments. The QMC calculations
      show that the structural transition directly causes the metal-insulator
      transition and a change in the coupling of vanadium spins. This change in the
      spin coupling results in a prediction of a momentum-independent magnetic
      excitation in the insulating state. While two-body correlations are important to
      set the stage for this transition, they do not change significantly when VO2
      becomes an insulator. These results show that it is now possible to account for
      electron correlations in a quantitatively accurate way that is also specific to
      materials.

PMID- 25978246
TI  - Probing Dirac fermion dynamics in topological insulator Bi2Se3 films with a
      scanning tunneling microscope.
AB  - Scanning tunneling microscopy and spectroscopy have been used to investigate the
      femtosecond dynamics of Dirac fermions in the topological insulator Bi2Se3
      ultrathin films. At the two-dimensional limit, bulk electrons become quantized
      and the quantization can be controlled by the film thickness at a single
      quintuple layer level. By studying the spatial decay of standing waves
      (quasiparticle interference patterns) off steps, we measure directly the energy
      and film thickness dependence of the phase relaxation length lphi and inelastic
      scattering lifetime tau of topological surface-state electrons. We find that tau
      exhibits a remarkable (E - EF)(-2) energy dependence and increases with film
      thickness. We show that the features revealed are typical for electron-electron
      scattering between surface and bulk states.

PMID- 25978245
TI  - Quantum Oscillations, Thermoelectric Coefficients, and the Fermi Surface of
      Semimetallic WTe2.
AB  - We present a study of angle-resolved quantum oscillations of electric and
      thermoelectric transport coefficients in semimetallic WTe2, which has the
      particularity of displaying a large B(2) magnetoresistance. The Fermi surface
      consists of two pairs of electronlike and holelike pockets of equal volumes in a
      "Russian doll" structure. The carrier density, Fermi energy, mobility, and the
      mean-free path of the system are quantified. An additional frequency is observed
      above a threshold field and attributed to the magnetic breakdown across two
      orbits. In contrast to all other dilute metals, the Nernst signal remains linear
      in the magnetic field even in the high-field (omegactau?1) regime. Surprisingly,
      none of the pockets extend across the c axis of the first Brillouin zone, making
      the system a three-dimensional metal with moderate anisotropy in Fermi velocity,
      yet a large anisotropy in the mean-free path.

PMID- 25978247
TI  - Chiral tunneling of topological states: towards the efficient generation of spin
      current using spin-momentum locking.
AB  - We show that the interplay between chiral tunneling and spin-momentum locking of
      helical surface states leads to spin amplification and filtering in a 3D
      topological insulator (TI). Our calculations show that the chiral tunneling
      across a TI pn junction allows normally incident electrons to transmit, while the
      rest are reflected with their spins flipped due to spin-momentum locking. The net
      result is that the spin current is enhanced while the dissipative charge current
      is simultaneously suppressed, leading to an extremely large, gate-tunable spin-to
      charge current ratio (~20) at the reflected end. At the transmitted end, the
      ratio stays close to 1 and the electrons are completely spin polarized. 

PMID- 25978248
TI  - Electronic properties of molecules and surfaces with a self-consistent
      interatomic van der Waals density functional.
AB  - How strong is the effect of van der Waals (vdW) interactions on the electronic
      properties of molecules and extended systems? To answer this question, we derived
      a fully self-consistent implementation of the density-dependent interatomic vdW
      functional of Tkatchenko and Scheffler [Phys. Rev. Lett. 102, 073005 (2009)]. Not
      surprisingly, vdW self-consistency leads to tiny modifications of the structure,
      stability, and electronic properties of molecular dimers and crystals. However,
      unexpectedly large effects were found in the binding energies, distances, and
      electrostatic moments of highly polarizable alkali-metal dimers. Most
      importantly, vdW interactions induced complex and sizable electronic charge
      redistribution in the vicinity of metallic surfaces and at organic-metal
      interfaces. As a result, a substantial influence on the computed work functions
      was found, revealing a nontrivial connection between electrostatics and long
      range electron correlation effects. 

PMID- 25978249
TI  - Subdecoherence time generation and detection of orbital entanglement in quantum
      dots.
AB  - Recent experiments have demonstrated subdecoherence time control of individual
      single-electron orbital qubits. Here we propose a quantum-dot-based scheme for
      generation and detection of pairs of orbitally entangled electrons on a time
      scale much shorter than the decoherence time. The electrons are entangled, via
      two-particle interference, and transferred to the detectors during a single
      cotunneling event, making the scheme insensitive to charge noise. For
      sufficiently long detector dot lifetimes, cross-correlation detection of the dot
      charges can be performed with real-time counting techniques, providing for an
      unambiguous short-time Bell inequality test of orbital entanglement. 

PMID- 25978250
TI  - Electron spin polarization by isospin ordering in correlated two-layer quantum
      Hall systems.
AB  - Enhancement of the electron spin polarization in a correlated two-layer, two
      dimensional electron system at a total Landau level filling factor of 1 is
      reported. Using resistively detected nuclear magnetic resonance, we demonstrate
      that the electron spin polarization of two closely spaced two-dimensional
      electron systems becomes maximized when interlayer Coulomb correlations establish
      spontaneous isospin ferromagnetic order. This correlation-driven polarization
      dominates over the spin polarizations of competing single-layer fractional
      quantum Hall states under electron density imbalances. 

PMID- 25978251
TI  - Composite fermions with a warped Fermi contour.
AB  - Via measurements of commensurability features near the Landau filling factor
      nu=1/2, we probe the shape of the Fermi contour for hole-flux composite fermions
      confined to a wide GaAs quantum well. The data reveal that the composite fermions
      are strongly influenced by the characteristics of the Landau level in which they
      are formed. In particular, their Fermi contour is warped when their Landau level
      originates from a hole band with significant warping. 

PMID- 25978252
TI  - Geometric quantum noise of spin.
AB  - The presence of geometric phases is known to affect the dynamics of the systems
      involved. Here, we consider a quantum degree of freedom, moving in a dissipative
      environment, whose dynamics is described by a Langevin equation with quantum
      noise. We show that geometric phases enter the stochastic noise terms.
      Specifically, we consider small ferromagnetic particles (nanomagnets) or quantum
      dots close to Stoner instability, and investigate the dynamics of the total
      magnetization in the presence of tunneling coupling to the metallic leads. We
      generalize the Ambegaokar-Eckern-Schon effective action and the corresponding
      semiclassical equations of motion from the U(1) case of the charge degree of
      freedom to the SU(2) case of the magnetization. The Langevin forces (torques) in
      these equations are strongly influenced by the geometric phase. As a first but
      nontrivial application, we predict low temperature quantum diffusion of the
      magnetization on the Bloch sphere, which is governed by the geometric phase. We
      propose a protocol for experimental observation of this phenomenon. 

PMID- 25978253
TI  - Tuning localized transverse surface plasmon resonance in electricity-selected
      single-wall carbon nanotubes by electrochemical doping.
AB  - Localized surface-plasmon resonance affects the optical absorption and scattering
      of nanosized materials. The intensities and peak energies of the surface plasmons
      strongly depend on the carrier density; thus, the optical absorption peaks
      originating from the surface-plasmon resonance can be manipulated by the density
      of injected carriers. In single-wall carbon nanotubes (SWCNTs), the correct
      identification of surface-plasmon resonance modes is of great interest due to
      their emerging plasmonic and optoelectronic applications. Here, we demonstrate
      that high-carrier injection by electric double layers can induce a transverse
      surface-plasmon peak in aggregated, electricity-selected SWCNTs. In contrast to
      the well-discussed surface-plasmon resonance mode, whose polarization is parallel
      to the axis and whose resonance frequency is located in the THz region, our
      identified mode, which was normal to the axis, was located in the near-infrared
      range. In addition, our mode's peak position and intensities were tunable by
      carrier injections, indicating a route to control plasmonic optical processes by
      electric double-layer carrier injections using ionic liquid. 

PMID- 25978254
TI  - Random flips of electric field in microwave-induced states with spontaneously
      broken symmetry.
AB  - In a two-dimensional electron system subject to microwaves and a magnetic field,
      photovoltages emerge. They can be separated into two components originating from
      built-in electric fields and electric field domains arising from spontaneous
      symmetry breaking. The latter occurs in the zero resistance regime only and
      manifests itself in pulsed behavior, synchronous across the sample. The pulses
      show sign reversal. This implies a flip of the field in each domain, consistent
      with the existence of two equally probable electric field domain configurations
      due to the spontaneous symmetry breaking. 

PMID- 25978255
TI  - Electronic Properties of BaFe2As2 upon Doping and Pressure: The Prominent Role of
      the As p Orbitals.
AB  - Using high-resolution, lifetime removed, x-ray absorption spectroscopy at the As
      K edge, we evidence the strong sensitivity of the As electronic structure upon
      electron doping with Co or pressure change in BaFe2As2, at room temperature. Our
      results unravel the prominent role played by As-4p orbitals in the electronic
      properties of the Fe pnictide superconductors. We propose a unique picture to
      describe the overall effect of both external parameter doping and pressure,
      resolving the apparent contradiction between angle-resolved photoemission
      spectroscopy, transport, and absorption results, with the As-p states as a key
      ingredient.

PMID- 25978256
TI  - Constraining quantum critical dynamics: (2+1)D Ising model and beyond.
AB  - Quantum critical (QC) phase transitions generally lead to the absence of
      quasiparticles. The resulting correlated quantum fluid, when thermally excited,
      displays rich universal dynamics. We establish nonperturbative constraints on the
      linear-response dynamics of conformal QC systems at finite temperature, in
      spatial dimensions above 1. Specifically, we analyze the large frequency or
      momentum asymptotics of observables, which we use to derive powerful sum rules
      and inequalities. The general results are applied to the O(N) Wilson-Fisher fixed
      point, describing the QC Ising model when N=1. We focus on the order parameter
      and scalar susceptibilities, and the dynamical shear viscosity. Connections to
      simulations, experiments, and gauge theories are made. 

PMID- 25978257
TI  - Kondo breakdown in topological Kondo insulators.
AB  - Motivated by the observation of light surface states in SmB6, we examine the
      effects of surface Kondo breakdown in topological Kondo insulators. We present
      both numerical and analytic results which show that the decoupling of the
      localized moments at the surface disturbs the compensation between light and
      heavy electrons and dopes the Dirac cone. Dispersion of these uncompensated
      surface states is dominated by intersite hopping, which leads to much lighter
      quasiparticles. These surface states are also highly durable against the effects
      of surface magnetism and decreasing thickness of the sample.

PMID- 25978258
TI  - Field-dependent size and shape of single magnetic Skyrmions.
AB  - The atomic-scale spin structure of individual isolated Skyrmions in an ultrathin
      film is investigated in real space by spin-polarized scanning tunneling
      microscopy. Their axial symmetry as well as their unique rotational sense is
      revealed by using both out-of-plane and in-plane sensitive tips. The size and
      shape of Skyrmions change as a function of the magnetic field. An analytical
      expression for the description of Skyrmions is proposed and applied to connect
      the experimental data to the original theoretical model describing chiral
      Skyrmions. Thereby, the relevant material parameters responsible for Skyrmion
      formation can be obtained. 

PMID- 25978259
TI  - Distinct trivial phases protected by a point-group symmetry in quantum spin
      chains.
AB  - The ground state of the S=1 antiferromagnetic Heisenberg chain belongs to the
      Haldane phase--a well-known example of the symmetry-protected topological phase.
      A staggered field applied to the S=1 antiferromagnetic chain breaks all the
      symmetries that protect the Haldane phase as a topological phase, reducing it to
      a trivial phase. That is, the Haldane phase is then connected adiabatically to an
      antiferromagnetic product state. Nevertheless, as long as the symmetry under site
      centered inversion combined with a spin rotation is preserved, the phase is still
      distinct from another trivial phase. We demonstrate the existence of such
      distinct symmetry-protected trivial phases using a field-theoretical approach and
      numerical calculations. Furthermore, a general proof and a nonlocal order
      parameter are given in terms of a matrix-product state formulation.

PMID- 25978260
TI  - Thermally mediated mechanism to enhance magnetoelectric coupling in
      multiferroics.
AB  - The main roadblock on the way to practical realization of magnetoelectric devices
      is the lack of multiferroics with strong magnetoelectric coupling. We propose an
      unusual route to dramatically enhance this coupling through a thermally mediated
      mechanism. Such a thermally mediated magnetoelectric effect is quantified by an
      isentropic rather than isothermal magnetoelectric response and is computed here
      from first principles. A robust enhancement of the magnetoelectric coupling is
      predicted for both naturally occurring and heterostructured materials. 

PMID- 25978261
TI  - Shortcut to adiabaticity in the Lipkin-Meshkov-Glick model.
AB  - We study transitionless quantum driving in an infinite-range many-body system
      described by the Lipkin-Meshkov-Glick model. Despite the correlation length being
      always infinite the closing of the gap at the critical point makes the driving
      Hamiltonian of increasing complexity also in this case. To this aim we develop a
      hybrid strategy combining a shortcut to adiabaticity and optimal control that
      allows us to achieve remarkably good performance in suppressing the defect
      production across the phase transition. 

PMID- 25978263
TI  - Electric field controlled columnar and planar patterning of cholesteric colloids.
AB  - We study how dispersions of colloidal particles in a cholesteric liquid crystal
      behave under a time-dependent electric field. By controlling the amplitude and
      shape of the applied field wave, we show that the system can be reproducibly
      driven out of equilibrium through different kinetic pathways and navigated
      through a glassylike free energy landscape encompassing many competing metastable
      equilibria. Such states range from simple Saturn rings to complex structures
      featuring amorphous defect networks, or stacks of disclination loops. A
      nonequilibrium electric field can also trigger the alignment of particles into
      columnar arrays, through defect-mediated force impulses, or their repositioning
      within a plane. Our results are promising in terms of providing new avenues
      towards controlled patterning and self-assembly of soft colloid-liquid crystal
      composite materials. 

PMID- 25978262
TI  - Visualizing the mixed bonding properties of liquid boron with high-resolution x
      ray Compton scattering.
AB  - Bonding characteristics of liquid boron at 2500 K are studied by using high
      resolution Compton scattering. An excellent agreement is found between the
      measurements and the corresponding Car-Parrinello molecular dynamics simulations.
      Covalent bond pairs are clearly shown to dominate in liquid boron along with the
      coexistence of diffuse pairs. Our study reveals the complex bonding pattern of
      liquid boron and gives insight into the unusual properties of this high
      temperature liquid. 

PMID- 25978264
TI  - Fraction of clogging configurations sampled by granular hopper flow.
AB  - We measure the fraction F of flowing grain configurations that precede a clog,
      based on the average mass discharged between clogging events for various aperture
      geometries. By tilting the hopper, we demonstrate that F is a function of the
      hole area projected in the direction of the exiting grain velocity. By varying
      the length of slits, we demonstrate that grains clog in the same manner as if
      they were flowing out of a set of smaller independent circular openings. The
      collapsed data for F can be fit to a decay that is exponential in hole width
      raised to the power of the system dimensionality. This is consistent with a
      simple model in which individual grains near the hole have a large but constant
      probability to precede a clog. Such a picture implies that there is no sharp
      clogging transition, and that all hoppers have a nonzero probability to clog. 

PMID- 25978265
TI  - Granular segregation driven by particle interactions.
AB  - We report the results of an experimental study of particle-particle interactions
      in a horizontally shaken granular layer that undergoes a second order phase
      transition from a binary gas to a segregation liquid as the packing fraction C is
      increased. By focusing on the behavior of individual particles, the effect of C
      is studied on (1) the process of cluster formation, (2) cluster dynamics, and (3)
      cluster destruction. The outcomes indicate that the segregation is driven by two
      mechanisms: attraction between particles with the same properties and random
      motion with a characteristic length that is inversely proportional to C. All
      clusters investigated are found to be transient and the probability distribution
      functions of the separation times display a power law tail, indicating that the
      splitting probability decreases with time. 

PMID- 25978266
TI  - Dynamics of a Volvox embryo turning itself inside out.
AB  - Deformations of cell sheets are ubiquitous in early animal development, often
      arising from a complex and poorly understood interplay of cell shape changes,
      division, and migration. Here, we explore perhaps the simplest example of cell
      sheet folding: the "inversion" process of the algal genus Volvox, during which
      spherical embryos turn themselves inside out through a process hypothesized to
      arise from cell shape changes alone. We use light sheet microscopy to obtain the
      first three-dimensional visualizations of inversion in vivo, and develop the
      first theory of this process, in which cell shape changes appear as local
      variations of intrinsic curvature, contraction and stretching of an elastic
      shell. Our results support a scenario in which these active processes function in
      a defined spatiotemporal manner to enable inversion. 

PMID- 25978267
TI  - Anomalous diffusion in fractal globules.
AB  - The fractal globule state is a popular model for describing chromatin packing in
      eukaryotic nuclei. Here we provide a scaling theory and dissipative particle
      dynamics computer simulation for the thermal motion of monomers in the fractal
      globule state. Simulations starting from different entanglement-free initial
      states show good convergence which provides evidence supporting the existence of
      a unique metastable fractal globule state. We show monomer motion in this state
      to be subdiffusive described by ?X(2)(t)?~t(alphaF) with alphaF close to 0.4.
      This result is in good agreement with existing experimental data on the chromatin
      dynamics, which makes an additional argument in support of the fractal globule
      model of chromatin packing.

PMID- 25978268
TI  - Multistable jittering in oscillators with pulsatile delayed feedback.
AB  - Oscillatory systems with time-delayed pulsatile feedback appear in various
      applied and theoretical research areas, and received a growing interest in recent
      years. For such systems, we report a remarkable scenario of destabilization of a
      periodic regular spiking regime. At the bifurcation point numerous regimes with
      nonequal interspike intervals emerge. We show that the number of the emerging, so
      called "jittering" regimes grows exponentially with the delay value. Although
      this appears as highly degenerate from a dynamical systems viewpoint, the
      "multijitter" bifurcation occurs robustly in a large class of systems. We observe
      it not only in a paradigmatic phase-reduced model, but also in a simulated
      Hodgkin-Huxley neuron model and in an experiment with an electronic circuit. 

PMID- 25978269
TI  - Generalized minimal principle for rotor filaments.
AB  - To a reaction-diffusion medium with an inhomogeneous anisotropic diffusion tensor
      D, we add a fourth spatial dimension such that the determinant of the diffusion
      tensor is constant in four dimensions. We propose a generalized minimal principle
      for rotor filaments, stating that the scroll wave filament strives to minimize
      its surface area in the higher-dimensional space. As a consequence, stationary
      scroll wave filaments in the original 3D medium are geodesic curves with respect
      to the metric tensor G=det(D)D(-1). The theory is confirmed by numerical
      simulations for positive and negative filament tension and a model with a non
      stationary spiral core. We conclude that filaments in cardiac tissue with
      positive tension preferentially reside or anchor in regions where cardiac cells
      are less interconnected, such as portions of the cardiac wall with a large number
      of cleavage planes.

PMID- 25978270
TI  - Carbon cycle in advanced coal chemical engineering.
AB  - This review summarizes how the carbon cycle occurs and how to reduce CO2
      emissions in highly efficient carbon utilization from the most abundant carbon
      source, coal. Nowadays, more and more attention has been paid to CO2 emissions
      and its myriad of sources. Much research has been undertaken on fossil energy and
      renewable energy and current existing problems, challenges and opportunities in
      controlling and reducing CO2 emission with technologies of CO2 capture,
      utilization, and storage. The coal chemical industry is a crucial area in the
      (CO2 value chain) Carbon Cycle. The realization of clean and effective conversion
      of coal resources, improving the utilization and efficiency of resources, whilst
      reducing CO2 emissions is a key area for further development and investigation by
      the coal chemical industry. Under a weak carbon mitigation policy, the value and
      price of products from coal conversion are suggested in the carbon cycle. 

PMID- 25978271
TI  - Ambulatory blood pressure and blood pressure load responses to low sodium
      intervention in Han Chinese population.
AB  - We aimed to illustrate ambulatory blood pressure monitoring parameters responses
      to low sodium intake and their differences between salt-sensitive and non-salt
      sensitive individuals. A total of 186 participants were included in this
      analysis. Twenty-four hour, day-time and night-time blood pressure (BP) and BP
      load decreased during low sodium intervention, especially in salt-sensitive (SS)
      group. After multivariable adjustment, 24-h systolic BP, diastolic BP, mean
      arterial pressure and BP load responses to low sodium intervention of SS
      individuals were more pronounced than those of non-salt-sensitive individuals.
      Thus, reducing salt intake is potentially needed for the prevention of
      hypertension, especially in SS individuals. 

PMID- 25978272
TI  - Self-compassion moderates body comparison and appearance self-worth's inverse
      relationships with body appreciation.
AB  - Although research on positive body image has increased, little research has
      explored which variables protect body appreciation during body-related threats.
      Self-compassion may be one such variable. Individuals high in self-compassion are
      mindful, kind, and nurturing toward themselves during situations that threaten
      their adequacy, while recognizing that being imperfect is part of "being human."
      In this study, we investigated whether two body-related threats (i.e., body
      comparison and appearance contingent self-worth) were more weakly related to body
      appreciation when self-compassion was high among an online sample of 263 women
      (Mage=35.26, SD=12.42). Results indicated that self-compassion moderated the
      inverse relationships between body related threats and body appreciation.
      Specifically, when self-compassion was very high, body comparison and appearance
      contingent self-worth were unrelated to body appreciation. However, when self
      compassion was low, these relationships were strong. Self-compassion, then, may
      help preserve women's body appreciation during body-related threats. 

PMID- 25978274
TI  - Lessons from rare diseases of cartilage and bone.
AB  - Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of
      more common disorders and identify potential therapeutic targets. Lessons from
      rare bone diseases contributed to the development of the most successful class of
      bone active agents, the bisphosphonates. More recent research on rare bone
      diseases has helped elucidate key pathways and identify new targets in bone
      resorption and bone formation including cathepsin K and sclerostin, for which
      drugs are now in clinical trials. By contrast, there has been much less focus on
      rare cartilage diseases and osteoarthritis (OA) remains a common disease with no
      effective therapy. Investigation of rare cartilage syndromes is identifying new
      potential targets in OA including GDF5 and lubricin. Research on the arthropathy
      of the ultra-rare disease alkaptonuria has identified several new features of the
      OA phenotype, including high density mineralized protrusions (HDMPs) which
      constitute a newly identified mechanism of joint destruction. 

PMID- 25978273
TI  - A qualitative analysis of parents' perceptions of weight talk and weight teasing
      in the home environments of diverse low-income children.
AB  - Research has shown that family weight talk and teasing are associated with child
      overweight status and unhealthy weight control behaviors. However, little is
      known about how weight talk and teasing are experienced in the home, how parents
      respond, and what factors influence whether weight talk and teasing occur. The
      main objective of this study is to qualitatively examine weight talk and teasing
      in the home environments of diverse low-income children. Parents (N=118) from a
      mixed-methods cross-sectional study were interviewed in their home. The majority
      of parents (90% female; mean age=35 years.) were from minority (65% African
      American) and low income (<$25,000/year) households. A grounded theory analysis
      found the following themes: weight talk contradictions, overt and covert weight
      talk/teasing, reciprocal teasing, and cultural factors related to weight
      talk/teasing. These themes should be addressed when developing family-based
      interventions to reduce weight talk and teasing in the home environment. 

PMID- 25978275
TI  - A new rearranged tricyclic abietane diterpenoid from Salvia chloroleuca Rech. f.
      & Allen.
AB  - Phytochemical investigation of the roots of Salvia chloroleuca led to the
      isolation and identification of a new rearranged abietane diterpenoid (1). Its
      structure was elucidated by interpretation of the 1D and 2D NMR spectra and
      completed by the analysis of the HR-ESI-MS data. Compound 1 is the secondly
      reported compound on a rearranged tricyclic abietane (4,5-seco-5,10-friedo
      abietane) diterpenoid with a ketal functionality between C-2 and C-11. A
      plausible biosynthetic pathway of 1 was also proposed. 

PMID- 25978276
TI  - Hollow silica sphere colloidal crystals: insights into calcination dependent
      thermal transport.
AB  - Colloidal crystals consisting of monodisperse hollow silica spheres represent a
      well-defined porous material class, which features a range of interesting
      optical, mechanical, and thermal properties. These hierarchically structured
      materials comprise micropores within the silica network, which are confined to a
      thin shell (tens of nanometers) of a hollow sphere (hundreds of nanometers).
      Using simple calcination steps, we markedly change the internal microstructure,
      which we investigate by a multitude of characterization techniques, while the
      meso- and macrostructure remains constant. Most importantly the rearrangement of
      the silica condensation network leads to a reduction in the total surface area
      and loss of micropores as demonstrated by N2 sorption and hyperpolarized (129)Xe
      NMR studies. Spin-lattice relaxation shows a drastic increase of the rigidity of
      the amorphous network. These microstructural changes significantly influence the
      thermal conductivity through such a porous silica material. We demonstrate a
      remarkably low thermal conductivity of only 71 mW m(-1) K(-1) for a material of a
      comparatively high density of 1.04 kg m(-3) at 500  degrees C calcination
      temperature. This thermal conductivity increases up to 141 mW m(-1) K(-1) at the
      highest calcination temperature of 950  degrees C. The great strength of hollow
      silica sphere colloidal crystals lies in their hierarchical structure control,
      which allows further investigation of how the internal microstructure and the
      interfacial contact points affect the transport of heat. 

PMID- 25978277
TI  - Diagnostic Yield and Safety of Computed Tomography-guided Mediastinal Core Needle
      Biopsies.
AB  - PURPOSE: Mediastinal masses of various origins can be encountered on imaging in
      symptomatic or asymptomatic patients. We aimed to evaluate the diagnostic yield
      and complication rate of computed tomography (CT)-guided mediastinal core needle
      biopsies in a large population of patients presenting with mediastinal masses and
      to identify the factors that could influence these results. MATERIALS AND
      METHODS: In total, 293 consecutive CT-guided mediastinal biopsies, performed in
      285 patients with equivocal masses at a single center from 2006 to 2011, were
      included. Lesion characteristics, technical biopsy parameters, final diagnoses,
      diagnostic yields (number of biopsies that yielded a complete diagnosis divided
      by the total number of biopsies), and complication rates were recorded. RESULTS:
      Malignant diagnoses, including lymphoproliferative disorders (N=151, 53%) and
      lung cancers (N=54, 19%), were established in 233 cases (82%). Benign lesions
      were found in 52 procedures (18%), including sarcoidosis (N=19, 7%) and
      infections (N=17, 6%). The overall diagnostic yield was 87% and was lower for
      lymphoma residual masses (57%) than for initial diagnosis or relapses of known
      disease (90%). Complications occurred in 21 patients (7%), but only 2 patients
      (0.7%) required hospitalization for >12 hours. Neither the diagnostic yield nor
      the complication rate was influenced by the target characteristics or by
      technical parameters. CONCLUSIONS: CT-guided core needle biopsy of equivocal
      mediastinal masses is a minimally invasive procedure that is effective and safe,
      even in cases of small targets or targets in challenging locations.

PMID- 25978278
TI  - Photochemical Synthesis of Nepetanudone.
AB  - Nepetanudone and nepetaparnone have been suspected of being the products of a
      photochemical dimerization of nepetapyrone. Both are natural products found in a
      variety of Nepeta species. The synthesis of (+/-)-nepetapyrone and subsequent
      photochemical experiments are described. (+/-)-Nepetanudone was produced upon
      irradiation of (+/-)-nepetapyrone, while (+/-)-nepetaparnone, a diastereomer of
      nepetanudone, was not observed. 

PMID- 25978279
TI  - The end of life: using the revised Code.

PMID- 25978280
TI  - Dying Matters: making death part of the conversation.

PMID- 25978281
TI  - Symptoms and functional status of palliative care patients in Iceland.
AB  - BACKGROUND: Palliative care patients experience many debilitating symptoms and
      functional loss, but few longitudinal studies on the subject are available. AIMS:
      To assess the symptoms and functional status of patients admitted to specialised
      palliative care, to investigate whether changes occur over the admission period,
      and to establish whether symptoms and physical and cognitive function differ,
      based on the service setting. In addition, to participate in the development of
      the interRAI Palliative Care instrument (interRAI PC). METHODS: A prospective
      longitudinal study (N=123) was conducted at three time points: at admission to
      specialised palliative care, 14 days post-admission, and at discharge or death.
      The interRAI PC version 8 was used for data collection. Descriptive statistics
      were used, together with the Friedman statistical test and Wilcoxon post-hoc
      test. RESULTS: Patients experienced a wide spectrum of symptoms; the most
      frequent were fatigue, loss of appetite, pain, difficulty sleeping, insufficient
      nutritional intake and nausea. Some symptoms stayed relatively stable over time,
      but others increased, while physical and cognitive function decreased over time.
      The interRAI PC version 8 proved comprehensive and simple to use. CONCLUSIONS:
      Patients experienced a significant symptom burden and functional loss from
      admission to discharge or death. Symptoms indicating progressive deterioration
      became more frequent and severe, while physical and cognitive function decreased
      at all levels. Overall, inpatients had more symptoms and functional decline than
      home-care patients. The interRAI PC version 8 proved valuable in collecting
      clinical information and detecting changes over time as other interRAI suite
      instruments.

PMID- 25978282
TI  - Managing pain medications in long-term care: nurses' views.
AB  - The purpose of this study was to explore nurses' perceptions of their current
      practices related to administering pain medications to long-term care (LTC)
      residents. A cross-sectional survey design was used, including both quantitative
      and open-ended questions. Data were collected from 165 nurses (59% response rate)
      at nine LTC homes in southern Ontario, Canada. The majority (85%) felt that the
      medication administration system was adequate to help them manage residents' pain
      and 98% felt comfortable administering narcotics. In deciding to administer a
      narcotic, nurses were influenced by pain assessments, physician orders,
      diagnosis, past history, effectiveness of non-narcotics and fear of making dosage
      miscalculations or developing addictions. Finally, most nurses stated that they
      trusted the physicians and pharmacists to ensure orders were safe. These findings
      highlight nurses' perceptions of managing pain medications in LTC and related
      areas where continuing education initiatives for nurses are needed. 

PMID- 25978283
TI  - Patient blood management nurse vs transfusion nurse: is it time to merge?
AB  - For many years, nurses have performed the tasks related to blood transfusion
      monitoring and the associated quality-control documentation. There have been
      multiple job titles given to healthcare providers in this field: haemovigilance
      officer, transfusion practitioner, transfusion nurse, patient blood management
      (PBM) nurse, blood conservation nurse and blood management nurse. These titles
      share some overlap in tasks. In this article, the authors discuss Australian and
      US experiences of the historical transfusion nurse role, and the newer title of
      PBM nurse. The article will attempt to answer the question: is it time these two
      job titles and roles were merged into one, creating the evolved role of PBM
      nurse? It will define the unique nature of these roles and attempt to explore any
      differences between them. PBM is becoming a standard of care and embedded in
      institutions around the world. The transition and adoption of a joint role is
      timely, and the article also addresses the issue of appropriate staffing levels.
      PBM has become the overarching phrase that addresses the prevention of
      transfusion as well as the quality and safety needs of transfusion medicine. The
      authors propose it is time to merge the roles of the PBM nurse and the
      transfusion nurse, which would ultimately benefit patients, as well as more
      thoroughly address the needs of hospitals. 

PMID- 25978284
TI  - Relationships: from staff nurse to nurse consultant. Part 5: medical and PAMs.

PMID- 25978285
TI  - Saying the wrong thing.
AB  - Ed Freshwater discusses the perils of social media and the boundaries that
      separate compassion and professionalism. Whatever you do, he says, never add
      patients as friends on Facebook! 

PMID- 25978286
TI  - Do not attempt resuscitation: patients and families must have a say.
AB  - Patients and their relatives have the right to be consulted before a do not
      attempt resuscitation notice (DNAR) is placed on file by a health professional
      (Tracey v Cambridge University Hospitals NHS Foundation Trust and others [2014]).
      Failing to do so is a breach of the patient's right to respect for a private and
      family life under the European Convention of Human Rights, article 8 (Council of
      Europe, 1950). In this article, the author sets out the steps nurses must take to
      ensure that DNAR notices placed on the file of their patients are lawful.

PMID- 25978287
TI  - New CQC standards for healthcare delivery.
AB  - Emeritus Professor Alan Gasper, at the University of Southampton, discusses the
      launch of the latest Care Quality Commission fundamental standards of care which
      are now the health and social care benchmarks. These new regulations became
      effective on 1 April 2015. 

PMID- 25978288
TI  - Investigating clinical incidents: conclusions and recommendations.
AB  - In the second of a two-part column, John Tingle discusses the House of Commons
      Public Administration Select Committee (PASC) report on investigating clinical
      incidents in the NHS. 

PMID- 25978289
TI  - How can the nursing profession alleviate the burden of chronic pain?

PMID- 25978290
TI  - A social movement for quality.

PMID- 25978291
TI  - Survival of Patients With Mucinous Ovarian Carcinoma and Ovarian Metastases: A
      Population-Based Cancer Registry Study.
AB  - OBJECTIVES: Patients with mucinous ovarian carcinoma (MOC) generally have a
      favorable prognosis, although in advanced stage, prognosis is significantly worse
      compared to patients with serous ovarian carcinomas (SOCs). This might be due to
      the difficulties in distinguishing MOC from metastatic tumors. In the current
      study, we investigate prognosis of MOC compared to other types of ovarian cancer
      and to synchronous metastases to the ovary (sMO). MATERIALS AND METHODS: Age,
      laterality, International Federation of Gynecology and Obstetrics stage, tumor
      grade, treatment, and survival were extracted from the Eindhoven Cancer registry
      for all patients diagnosed with ovarian carcinomas or sMO between 1990 and 2012.
      Five-year survival analysis and Cox proportional hazards analysis were conducted.
      RESULTS: A total of 3556 patients with primary ovarian carcinoma (of which 474
      mucinous) and 289 with sMO were identified. In advanced stage, 5-year survival of
      patients with MOC was comparable to survival of patients with sMO (11% vs 11%, P
      = 0.32) and decreased compared to patients with SOC (26%, P < 0.01). For MOC,
      there was no clinically significant effect on 5-year survival of either debulking
      (12% vs 8%, P < 0.01) or chemotherapy (12% vs 10%, P = 0.02). CONCLUSIONS:
      Patients with advanced stage MOC have a worse prognosis than advanced stage SOC.
      Survival is almost identical to that of patients with sMO. Effects of
      chemotherapy and debulking are limited in patients with MOC, which may be
      explained by suboptimal treatment due to the admixture of metastases in advanced
      stage MOC. Methods to differentiate between primary MOC and metastatic disease
      are needed to provide optimal treatment and insight in prognosis.

PMID- 25978293
TI  - Gadolinium sulfate modified by formate to obtain optimized magneto-caloric
      effect.
AB  - Three new Gd(III) based coordination polymers [Gd2(C2H6SO)(SO4)3(H2O)2]n (1),
      {[Gd4(HCOO)2(SO4)5(H2O)6].H2O}n (2), and [Gd(HCOO)(SO4)(H2O)]n (3) were obtained
      by modifying gadolinium sulfate. With the gradual increase of the volume ratio of
      HCOOH and DMSO in synthesis, the formate anions begin to coordinate with metal
      centers; this results in the coordination numbers of sulfate anion increasing and
      the contents of water and DMSO molecules decreasing in target complexes.
      Accordingly, spin densities both per mass and per volume were enhanced step by
      step, which are beneficial for the magneto-caloric effect (MCE). Magnetic studies
      reveal that with the more formate anions present, the larger the negative value
      of magnetic entropy change (-DeltaSm) is. Complex 3 exhibits the largest -DeltaSm
      = 49.91 J kg(-1) K(-1) (189.51 mJ cm(-3) K(-1)) for T = 2 K and DeltaH = 7 T
      among three new complexes. 

PMID- 25978292
TI  - The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A
      Subanalysis of the Prospective Multicenter ROBOT Study.
AB  - OBJECTIVE: The value of the serum tumor marker CA125 in borderline tumors of the
      ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and
      follow-up. The aim of the present project was to identify the predictive value of
      CA125 for stage and relapse. METHODS: CA125 data were extracted from the ROBOT
      multicenter study of patients with BOT treated between 1998 and 2008 in 24 German
      centers. While patients' data were retrieved retrospectively from hospital
      records and clinical tumor registries, follow-up and independent central
      pathology review were performed prospectively. RESULTS: We identified 127
      patients from the ROBOT database fulfilling the eligibility criterion of
      available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased
      CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4%
      with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%)
      patients experienced a relapse. Multivariate analysis identified raised CA125,
      young age, and serous histology as independent predictors of peritoneal implants
      of any type at initial presentation. Raised CA125 at initial diagnosis was,
      however, not an independent predictor of future relapse. DISCUSSION: Elevated
      CA125 seems to be associated with the presence of peritoneal implants of any type
      at initial diagnosis of serous BOT, but failed to have any independent predictive
      value on future relapse. Prospective multicenter studies are warranted to
      evaluate CA125 measurements in the follow-up management of BOT.

PMID- 25978294
TI  - Shape transformations of soft matter governed by bi-axial stresses.
AB  - Rational design of the programmable soft matter requires understanding of the
      effect of a complex metric on shape transformations of thin non-Euclidean sheets.
      In the present work, we explored experimentally and using simulations how
      simultaneous or consecutive application of two orthogonal perturbations to thin
      patterned stimuli-responsive hydrogel sheets affects their three-dimensional
      shape transformations. The final shape of the sheet is governed by the metric,
      but not the order, in which the perturbations are applied to the system, and is
      determined by the competition of small-scale bidirectional stresses. In addition,
      a new, unexpected transition from a planar state to an equilibrium helical shape
      of the hydrogel sheet is observed via a mechanism that is yet to be explained. 

PMID- 25978295
TI  - Quantifying the effects of temperature and salinity on partitioning of
      hydrophobic organic chemicals to silicone rubber passive samplers.
AB  - Nowadays, passive sampling is a widely applied technique to determine freely
      dissolved aqueous concentrations of hydrophobic organic chemicals (HOCs), such as
      polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs).
      Crucial to the measurements are sampler-water partition coefficients, which are
      generally determined in the laboratory under "standard conditions" (in freshwater
      at 20  degrees C). Theoretically, however, the coefficients are dependent on
      environmental conditions, such as temperature and salinity. Yet, there are
      insufficient experimental data in the scientific literature to prove this for
      different polymers. Several polymers are already being applied during field
      monitoring, however, and neglecting any effects may lead to imprecise results. In
      the present study, we therefore quantified the effects of temperature and
      salinity on the sampler-water partition coefficients of PAHs and PCBs for
      silicone rubber, a material used in Dutch passive sampling monitoring campaigns.
      The results demonstrated a chemical-specific and hydrophobicity-dependent
      temperature effect, being independent of salinity, and a chemical- and
      temperature-independent salinity effect. Based on the obtained data, location
      specific silicone rubber-water partition coefficients (Ksr-w; adjusted for
      temperature and salinity) can be calculated. The impact of applying such location
      specific values was demonstrated using the Dutch passive sampling field
      monitoring database, covering ten years of PAH and PCB data for several
      locations. Adjusting the Ksr-w values resulted in aqueous concentrations that
      were lowered by a factor of 1.6 on average. The reduction was rather constant
      because of the manner of sampling (under nonequilibrium conditions and using
      performance reference compounds) and calculating. When sampling under equilibrium
      conditions in seawater at temperatures at about freezing, and/or applying
      different calculation approaches, the adjustment effect can potentially increase
      up to a factor of about 5-6 for the more hydrophobic PAHs and PCBs. Although this
      study exclusively focused on silicone rubber, qualitatively the results will also
      apply to other passive sampling materials. 

PMID- 25978296
TI  - SuperQuant: A Data Processing Approach to Increase Quantitative Proteome
      Coverage.
AB  - SuperQuant is a quantitative proteomics data processing approach that uses
      complementary fragment ions to identify multiple coisolated peptides in tandem
      mass spectra allowing for their quantification. This approach can be applied to
      any shotgun proteomics data set acquired with high mass accuracy for
      quantification at the MS(1) level. The SuperQuant approach was developed and
      implemented as a processing node within the Thermo Proteome Discoverer 2.x. The
      performance of the developed approach was tested using dimethyl-labeled HeLa
      lysate samples having a ratio between channels of 10(heavy):4(medium):1(light).
      Peptides were fragmented with collision-induced dissociation using isolation
      windows of 1, 2, and 4 Th while recording data both with high-resolution and low
      resolution. The results obtained using SuperQuant were compared to those using
      the conventional ion trap-based approach (low mass accuracy MS(2) spectra), which
      is known to achieve high identification performance. Compared to the common high
      resolution approach, the SuperQuant approach identifies up to 70% more peptide
      spectrum matches (PSMs), 40% more peptides, and 20% more proteins at the 0.01 FDR
      level. It identifies more PSMs and peptides than the ion trap-based approach.
      Improvements in identifications resulted in up to 10% more PSMs, 15% more
      peptides, and 10% more proteins quantified on the same raw data. The developed
      approach does not affect the accuracy of the quantification and observed
      coefficients of variation between replicates of the same proteins were close to
      the values typical for other precursor ion-based quantification methods. The raw
      data is deposited to ProteomeXchange (PXD001907). The developed node is available
      for testing at https://github.com/caetera/SuperQuantNode.

PMID- 25978297
TI  - Controllable Tuning Plasmonic Coupling with Nanoscale Oxidation.
AB  - The nanoparticle on mirror (NPoM) construct is ideal for the strong coupling of
      localized plasmons because of its simple fabrication and the nanometer-scale gaps
      it offers. Both of these are much harder to control in nanoparticle dimers. Even
      so, realizing controllable gap sizes in a NPoM remains difficult and continuous
      tunability is limited. Here, we use reactive metals as the mirror so that the
      spacing layer of resulting metal oxide can be easily and controllably created
      with specific thicknesses resulting in continuous tuning of the plasmonic
      coupling. Using Al as a case study, we contrast different approaches for
      oxidation including electrochemical oxidation, thermal annealing, oxygen plasma
      treatments, and photo-oxidation by laser irradiation. The thickness of the
      oxidation layer is calibrated with depth-mode X-ray photoemission spectroscopy
      (XPS). These all consistently show that increasing the thickness of the oxidation
      layer blue-shifts the plasmonic resonance peak while the transverse mode remains
      constant, which is well matched by simulations. Our approach provides a facile
      and reproducible method for scalable, local and controllable fabrication of NPoMs
      with tailored plasmonic coupling, suited for many applications of sensing,
      photochemistry, photoemission, and photovoltaics. 

PMID- 25978298
TI  - In Situ Derivatization of an Intrinsic Iron Impurity as a Surface-Confined
      Iron(II)tris(2,2'-bipyridine) Complex on MWCNT and Its Application to Selective
      Electrochemical Sensing of DNA's Purine Bases.
AB  - The derivatization of an intrinsic iron impurity in a carbon nanotube (CNT-*Fe,
      *Fe-intrinsic, and redox-active iron impurity) as a functional molecular system
      has been challenging to realize. There are certain limitations on the
      derivatization of such iron impurities such as low concentration and limited
      accessibility. Herein, we report an in situ electroassisted derivatization of an
      intrinsic and redox-active iron impurity in a multiwalled carbon nanotube (MWCNT
      *Fe, *Fe, 2.1 wt %) as MWCNT-*Fe(bpy)3(2+), where Fe(bpy)3(2+) =
      iron(II)tris(2,2'-bipyridine) complex and bpy = 2,2'-bipyridine. The hybrid
      complex was prepared by the electrochemical treatment of a 2,2'-bipyridine ligand
      adsorbed {MWCNT-*Fe + Nafion} modified glassy carbon electrode in pH 7 phosphate
      buffer solution. This new MWCNT-*Fe(bpy)3(2+) hybrid electrode showed well
      defined, stable redox at E1/2 = 830 mV with a peak-to-peak separation (DeltaEp)
      of 72 mV in a neutral pH solution. This is quite different from an ex situ Nafion
      Fe(bpy)3(2+) complex system that showed an unstable response at neutral pH. This
      in situ approach can allow the redox-active iron impurity in the CNTs to be
      quantified using the current signal of the Fe(bpy)3(2+) hybrid system. This MWCNT
      *Fe(bpy)3(2+) hybrid modified electrode was further used as an electrochemical
      detector for selective and separation-less flow injection analysis of DNA's
      purine bases, adenine and guanine, without interference from pyrimidine bases,
      cytosine, and thymine at different oxidative detection potentials of 1 V (for
      adenine and guanine) and 0.7 V vs Ag/AgCl (for guanine) using the pH 7 phosphate
      buffer solution as a carrier system. 

PMID- 25978299
TI  - Radiological and chemical toxicity due to ingestion of uranium through drinking
      water in the environment of Bangalore, India.
AB  - Groundwater samples collected from 96 bore wells in the study area (city of
      Bangalore) were analysed for concentration of natural uranium using laser-induced
      fluorimetry. The risk to the population of the region associated with
      radiological and chemical toxicity of uranium due to its ingestion through
      drinking water over a lifetime was estimated. The concentration of uranium was
      found to be in the range 0.136 to 2027.5 MUg L(-1) with an average value of 92.42
      MUg L(-1). In the present study, about 61% of the samples show concentrations of
      uranium within the safe limit of 30 MUg L(-1) as set by the world health
      organisation. The radiological risk estimated as lifetime cancer risk is in the
      range 4.3  *  10(-7) to 6.4  *  10(-3) with an average of 2.9  *  10(-4). The
      chemical toxicity risk measured as lifetime average daily dose is found to range
      from 0.005 to 75.42 MUg kg(-1) d(-1). The reference dose estimated as 1.12 MUg
      kg(-1) d(-1) was used to assess the chemical toxicity. The results indicate that
      the chemical toxicity due to ingestion of uranium through drinking water is of
      more concern than the radiological toxicity. The present study, being the first
      of its kind in this region, will augment the database of uranium in groundwater.

PMID- 25978300
TI  - Exosomes as mediators of intercellular communication: clinical implications.
AB  - Cells of multicellular organisms exchange informative signals by diverse
      mechanisms. Recent findings uncovered the special role of extracellular vesicles,
      especially exosomes, in intercellular communication. Exosomes, present in all
      tested human bodily fluids, carry various functional compounds including
      proteins, lipids, and diverse RNA molecules. The composition of exosome cargo in
      vivo is likely formed by a regulated selection of specific components and can
      express the current status of the exosome-secreting cell. Therefore, particular
      emphasis is now placed on the extremely high potential of exosomes as essentially
      noninvasive prognostic and diagnostic biomarkers, but also as therapeutic
      nanocarriers, especially after the discovery that their cargo as well as cell
      targeting specificity could be shaped in vitro. In addition, targeting the
      exosomes mediating pathological intercellular communication may also express high
      therapeutic potential. Hence, numerous studies are conducted to explore the
      profile and function of exosomes and their cargo in health and disease and to
      shape their properties to facilitate their clinical application. The present
      review summarizes the current knowledge on the role of exosomes in different
      physiological and pathological mechanisms of intercellular communication with a
      particular focus on the use of exosomes in the diagnosis and treatment of various
      inflammatory, cardiovascular, metabolic, and neurodegenerative disorders as well
      as malignant neoplasms. 

PMID- 25978301
TI  - Gender Differences in Patients with Atrial Fibrillation Undergoing Electrical
      Cardioversion.
AB  - BACKGROUND: Current recommendations on the rhythm control strategy for treatment
      of atrial fibrillation (AF) are more restrictive than a decade ago. Gender may
      play a role in decisions on the management of AF, including application of
      electrical cardioversion. METHODS: We analyzed clinical characteristics by gender
      in patients participating in the observational survey about stable patients
      underlying cardioversion in Spain (CARDIOVERSE) study (n=915), a survey of the
      practice of electrical cardioversion in 67 Spanish hospitals. We compared these
      data with those from a previous survey of electrical cardioversion in Spain
      (REVERSE study) performed 8 years previously. RESULTS: Patients undergoing
      electrical cardioversion were mainly men (76%). This finding was observed in all
      age groups, independently of symptoms. Men were younger (62+/-10 years vs. 69+/-9
      years; p<0.001), more frequently asymptomatic and had a lower prevalence of
      hypertension and a lower stroke risk. Among asymptomatic patients, the
      predominance of men was especially evident in older age groups (<65 years, men
      76%, women 24%; >=65 years, men 92%, women 8% (p<0.001). Compared with the
      REVERSE study, we observed a decrease in the percentage of women among patients
      undergoing electrical cardioversion (37% REVERSE vs. 24% CARDIOVERSE; p<0.001),
      mainly in older than 65 years. CONCLUSIONS: Our results support the hypothesis
      that gender is a determinant in decisions on the most appropriate strategy for
      managing AF. We observed a decrease in the percentage of women undergoing
      electrical cardioversion during the last decade, especially in older asymptomatic
      patients.

PMID- 25978302
TI  - Prevalence of concomitant medications in older HIV+ patients and comparison with
      general population.
AB  - OBJECTIVE: The increasing population of human immunodeficiency virus (HIV)
      infected elderly patients results in a higher number of comorbidities and greater
      incidence of polypharmacy in addition to antiretroviral therapy (ART). The aim of
      this study is to describe the use of concomitant medication in older HIV-infected
      patients and to compare it with older general population. METHODS: The study
      included HIV-positive outpatients (>49 years) who received ART in 2011. Co
      medication dispensed by pharmacies in that year was collected. Defined daily dose
      (DDD) for each drug was calculated by patient. A comparison was made between the
      use of co-medication among men between 50 and 64 years old in general population
      against the HIV-infected population. RESULTS: The study was based on 118 patients
      (77% men), of which 82% took at least one co-medication and 58% at least five.
      The commonest co-medications used by HIV-positive patients were antibiotics
      (44%); analgesics (44%); anti-inflammatories (39%); antacids (38%); and
      psycholeptics (38%). The medicines used for the greatest number of days per HIV
      positive patient were those related to the renin-angiotensin system; anti
      diabetics; lipid modifying agents; antithrombotics; and calcium channel blockers.
      In comparison with the general male population, a higher proportion of HIV
      infected patients used antibiotics (42 vs 30%, P = 0.018), antiepileptics (16 vs
      5%, P = 0.000), psycholeptics (35 vs 17%, P = 0.000) and COPD medications (14 vs
      7%, P = 0.008). The duration of antibiotics and psycholeptic use in HIV-infected
      patients was longer compared to the general population (P < 0.05). CONCLUSIONS:
      Older HIV-positive patients frequently take a higher number of co-medication,
      which increases the risk of adverse events, interactions with other medication,
      and may lead to poorer treatment adherence.

PMID- 25978303
TI  - In Vitro Selection for Small-Molecule-Triggered Strand Displacement and
      Riboswitch Activity.
AB  - An in vitro selection method for ligand-responsive RNA sensors was developed that
      exploited strand displacement reactions. The RNA library was based on the
      thiamine pyrophosphate (TPP) riboswitch, and RNA sequences capable of hybridizing
      to a target duplex DNA in a TPP regulated manner were identified. After three
      rounds of selection, RNA molecules that mediated a strand exchange reaction upon
      TPP binding were enriched. The enriched sequences also showed riboswitch
      activity. Our results demonstrated that small-molecule-responsive nucleic acid
      sensors can be selected to control the activity of target nucleic acid circuitry.

PMID- 25978304
TI  - Picosecond Dynamics of Avobenzone in Solution.
AB  - Avobenzone, a dibenzoylmethane compound commonly found in sunscreens, can
      photoisomerize after exposure to near-ultraviolet light. At equilibrium,
      avobenzone exists as a chelated enol characterized by a strong intramolecular
      hydrogen bond. Many nanosecond- to microsecond-scale experiments have shown that
      the photoisomerization involves several nonchelated enol (NCE) isomers and
      reaction paths, including some that reduce avobenzone's efficacy as a sunscreen.
      Because some of the NCE isomers are unstable, these experiments do not directly
      measure their spectroscopic signatures. Here, we report the dynamics of
      avobenzone on the picosecond time scale. We excite avobenzone at 350 nm and
      observe the formation and relaxation of new isomers and vibrationally excited
      species with broadband visible probe pulses and 266 nm probe pulses. Our results
      show the first direct evidence of two unstable NCE isomers and establish the
      lifetimes of and the branching ratio between these isomers. 

PMID- 25978305
TI  - High and stable photoelectrochemical activity of ZnO/ZnSe/CdSe/Cu(x)S core-shell
      nanowire arrays: nanoporous surface with Cu(x)S as a hole mediator.
AB  - Advanced materials for electrocatalytic and photoelectrochemical water splitting
      are key for taking advantage of renewable energy. In this study,
      ZnO/ZnSe/CdSe/Cu(x)S core-shell nanowire arrays with a nanoporous surface were
      fabricated via ion exchange and successive ionic layer adsorption and reaction
      (SILAR) processes. The ZnO/ZnSe/CdSe/Cu(x)S sample displays a high photocurrent
      density of 12.0 mA cm(-2) under AM 1.5G illumination, achieves the highest IPCE
      value of 89.5% at 500 nm at a bias potential of 0.2 V versus Ag/AgCl, and
      exhibits greatly improved photostability. The functions of the ZnSe, CdSe, and
      Cu(x)S layers in the ZnO/ZnSe/CdSe/Cu(x)S heterostructure were clarified. ZnSe is
      used as a passivation layer to reduce the trapping and recombination of charge
      carriers at the interfaces of the semiconductors. CdSe functions as a highly
      efficient visible light absorber and builds heterojunctions with the other
      components to improve the separation and transportation of the photoinduced
      electrons and holes. Cu(x)S serves as a passivation layer and an effective p-type
      hole mediator, which passivates the defects and surface states of the
      semiconductors and forms p-n junctions with CdSe to promote the hole
      transportation at the semiconductor-electrolyte interface. The nanoporous surface
      of the ZnO/ZnSe/CdSe/Cu(x)S core-shell nanowire arrays, together with the tunnel
      transportation of the charge carriers in the thin films of ZnSe and CdSe, also
      facilitates the kinetics of photoelectrochemical reactions and improves the
      optical absorption as well.

PMID- 25978306
TI  - High Performance and Long-Term Stability in Ambiently Fabricated Segmented Solid
      State Polymer Electrochromic Displays.
AB  - This work reports on the performance of a segmented polymer electrochromic
      display that was fabricated with solution-based processes in ambient atmosphere.
      An encapsulation process and the combination of structured wells for the polymer
      electrochrome and electrolyte layers as well as the use of a preoxidized counter
      polymer yields high contrasts and fast switching speeds. Asymmetric driving-with
      respect to time-of the display is investigated for the first time and the
      degradation effects in the electrochrome layer are analyzed and addressed to
      yield a stable device exceeding 100,000 switching cycles. A printed circuit board
      was integrated with the display, allowing the device to be run as a clock, where
      the segments only required short pulses to switch without the need for a constant
      current to maintain its state. Such an application pairs well with the advantages
      of electrochromic polymers, drawing on its high contrast, stability, and ability
      to maintain its colored or colorless state without the need for a constant power
      supply, to demonstrate the promise as well as the challenges of developing more
      sophisticated electrochromic devices.

PMID- 25978307
TI  - Probing the Solvent Accessibility of the [4Fe-4S] Cluster of the Hydrogenase
      Maturation Protein HydF from Thermotoga neapolitana by HYSCORE and 3p-ESEEM.
AB  - The catalytic site of [FeFe]-hydrogenase, the "H-cluster", composed of a [4Fe-4S]
      unit connected by a cysteinyl residue to a [2Fe] center coordinated by three CO,
      two CN(-), and a bridging dithiolate, is assembled in a complex maturation
      pathway, at present not fully characterized, involving three conserved proteins,
      HydG, HydE, and HydF. HydF is a complex enzyme, which is thought to act as a
      scaffold and carrier for the [2Fe] subunit of the H-cluster. This maturase
      protein contains itself a [4Fe-4S] cluster binding site, with three conserved
      cysteine residues and a noncysteinyl fourth ligand. In this work, we have
      exploited 3p-ESEEM and HYSCORE spectroscopies to get insight into the structure
      and the chemical environment of the [4Fe-4S] cluster of HydF from the
      hyperthermophilic organism Thermotoga neapolitana. The nature of the fourth
      ligand and the solvent accessibility of the active site comprising the [4Fe-4S]
      cluster are discussed on the basis of the spectroscopic results obtained upon H/D
      exchange. We propose that the noncysteinyl ligated Fe atom of the [4Fe-4S]
      cluster is the site where the [2Fe] subcluster precursor is anchored and finally
      processed to be delivered to the hydrogenase (HydA). 

PMID- 25978308
TI  - Firefighter Incident Rehabilitation: Interpreting Heart Rate Responses.
AB  - The primary objective of this observational study was to document the heart rate
      (HR) responses of firefighters during incident rehabilitation following
      firefighting activity in a high-rise building with a simulated fire on the 10th
      floor. Additionally, the study investigated potential factors, including
      firefighting workload, ambient temperature, firefighter movement, and individual
      characteristics, that may have affected HR during recovery. Firefighters (n =
      198) were assigned to perform a simulation of fire suppression, search and
      rescue, or material support during one of six firefighting trials that involved
      different crew sizes and ascent modes, and were performed in different
      environmental conditions. After completing the simulated firefighting activity,
      firefighters reported to a rehabilitation area on the 8th floor. The
      rehabilitation area was staffed by firefighter/paramedics. HR was monitored
      continuously during simulated firefighting activity and a 15-minute
      rehabilitation period. Average HR during rehabilitation (HRmean) was calculated
      and compared across trials. Simulated firefighting activity was performed in the
      summer in Virginia, USA, and ambient conditions varied among trials (mean +/- SD:
      31 +/- 4 degrees C; 46 +/- 15% relative humidity; 32 +/- 4 degrees C heat index).
      Duration of simulated firefighting activity ranged from 12.0 to 20.3 minutes
      among trials (mean: 15.4 +/- 5.2 minutes). Over all trials, mean peak HR during
      simulations was 173 +/- 18 beats.min(-1). Mean HR over all trials at entry into
      rehabilitation was 149 +/- 24 beats.min(-1). Following 15 minutes of recovery,
      mean HR over all trials was 126 +/- 23 beats.min(-1). Exploratory analyses
      revealed that higher workload during firefighting (stair trials), higher ambient
      temperature (>=30 degrees C), greater movement during rehabilitation (>=0.1 g
      force), higher age (>=45 years), and higher BMI (>=30.0 kg.m(-2)) were associated
      with higher HR responses during rehabilitation. During complex emergency
      operations, emergency medical service personnel will likely encounter
      considerable variability in HR responses upon initial evaluation and throughout
      rehabilitation. Following one bout of firefighting activity during a simulated
      fire scenario, HR decreased but remained elevated well above resting values
      following 15 minutes of rehabilitation. Based on current fire service
      recommendations, the majority of firefighters (88%) would not have been released
      from rehabilitation and eligible for reassignment after a 15-minute
      rehabilitation period following a brief bout of simulated firefighting activity.
      KEY WORDS: medical monitoring, cardiac strain, firefighting.

PMID- 25978309
TI  - Hybrid epidemics--a case study on computer worm conficker.
AB  - Conficker is a computer worm that erupted on the Internet in 2008. It is unique
      in combining three different spreading strategies: local probing, neighbourhood
      probing, and global probing. We propose a mathematical model that combines three
      modes of spreading: local, neighbourhood, and global, to capture the worm's
      spreading behaviour. The parameters of the model are inferred directly from
      network data obtained during the first day of the Conficker epidemic. The model
      is then used to explore the tradeoff between spreading modes in determining the
      worm's effectiveness. Our results show that the Conficker epidemic is an example
      of a critically hybrid epidemic, in which the different modes of spreading in
      isolation do not lead to successful epidemics. Such hybrid spreading strategies
      may be used beneficially to provide the most effective strategies for
      promulgating information across a large population. When used maliciously,
      however, they can present a dangerous challenge to current internet security
      protocols. 

PMID- 25978310
TI  - Association Study between Polycystic Ovarian Syndrome and the Susceptibility
      Genes Polymorphisms in Hui Chinese Women.
AB  - INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common
      endocrine-metabolic disorders. Evidence of familial aggregation analysis and
      different clinical traits among different regions and ethnicities indicated that
      the pathogenesis of PCOS is associated with multiple genetic and environmental
      factors. Our previous research had identified three susceptibility loci
      (rs2479106, DENND1A; rs13405728, LHCGR; rs13429458, THADA) for PCOS in Han
      Chinese women. The overall aim of this study was to investigate the relationship
      between three susceptibility gene polymorphisms and PCOS in Hui ethnic women.
      METHODS: 151 patients with PCOS (case group) and 99 healthy women (control group)
      were recruited from the Reproductive Medicine Center of the General Hospital of
      Ningxia Medical University. Clinical data and serum hormone characteristics of
      case and control groups were collected and analyzed. The three susceptibility
      single-nucleotide polymorphisms have been replicated in both case and control
      groups. Gene polymorphisms were detected by direct sequencing after polymerase
      chain reaction. RESULTS: The Body Mass Index, LH, LH/FSH ratio and total
      testosterone were significantly elevated in PCOS patients compared to control
      group (P<0.05). The frequencies of genotype and allele in rs13405728 were
      significantly different between the PCOS and the control groups (P<0.05). Of the
      SNP rs13405728, the PCOS cases with TT genotype stayed at a higher level of total
      testosterone, TG and LDL than those with the CC and CT genotypes. In contrary,
      there was no statistical difference between the two groups for SNP rs13429458 and
      rs2479106 (P>0.05). CONCLUSION: The present study suggested that the SNP
      rs13405728 in the LHCGR gene was associated with PCOS in Hui ethnic women, and
      its TT genotype characterized with higher level of TT, TG and LDL.

PMID- 25978312
TI  - Characteristics of randomized controlled trials designed for elderly: a
      systematic review.
AB  - OBJECTIVES: To quantify the proportion of randomized controlled trials (RCTs)
      specifically designed for elderly, and to assess their characteristics, as
      compared to RCTs not specifically designed for elderly. DESIGN: Review and
      synthesis of published literature. MEASUREMENTS: We searched PubMed for articles
      published in the year 2012. We included RCTs. Articles were excluded if not
      conducted with human subjects or if findings of secondary analyses were reported.
      A random sample of 10% was drawn and of this selection the following trial
      characteristics were extracted: sample size, disease category, age of sample, and
      age-related inclusion criteria. Clinical trials were defined to be specifically
      designed for elderly if a lower age cut-off of >= 55 years was used, or when
      participants had an average age of >= 70 years. RESULTS: The search strategy
      yielded 26,740 articles, from which a random sample was drawn, resulting in 2375
      articles. After exclusion, data was extracted from 1369 publications. Of these
      1369 RCTs, 96 (7%) were specifically designed for elderly. In comparison with
      trials not designed for older adults, trials designed for elderly contained a
      significantly larger median number of participants (125 vs. 80, p = 0.008)
      significantly more trials designed for elderly fell into the disease categories
      eye (6% vs. 2%, p = 0.005), musculoskeletal (13% vs. 7%, p = 0.023) and
      circulatory system (16% vs. 9%, p = 0.039). No significant difference was
      observed with regard to the other disease categories. CONCLUSION: There is a low
      proportion of RCTs specifically designed for elderly. As older patients will
      increasingly form the majority in medical practice, there is an urgent need for
      stronger evidence for the formulation of treatment guidelines specifically for
      older adults.

PMID- 25978311
TI  - Strand-Specific Quantitative Reverse Transcription-Polymerase Chain Reaction
      Assay for Measurement of Arenavirus Genomic and Antigenomic RNAs.
AB  - Arenaviruses are bi-segmented, single-stranded RNA viruses that cause significant
      human disease. The manner in which they regulate the replication of their genome
      is not well-understood. This is partly due to the absence of a highly sensitive
      assay to measure individual species of arenavirus replicative RNAs. To overcome
      this obstacle, we designed a quantitative reverse transcription (RT)-PCR assay
      for selective quantitation of each of the lymphocytic choriomeningitis virus
      (LCMV) genomic or antigenomic RNAs. During the course of assay design, we
      identified a nonspecific priming phenomenon whereby, in the absence of an RT
      primer, cDNAs complementary to each of the LCMV replicative RNA species are
      generated during RT. We successfully circumvented this nonspecific priming event
      through the use of biotinylated primers in the RT reaction, which permitted
      affinity purification of primer-specific cDNAs using streptavidin-coated magnetic
      beads. As proof of principle, we used the assay to map the dynamics of LCMV
      replication at acute and persistent time points and to determine the quantities
      of genomic and antigenomic RNAs that are incorporated into LCMV particles. This
      assay can be adapted to measure total S or L segment-derived viral RNAs and
      therefore represents a highly sensitive diagnostic platform to screen for LCMV
      infection in rodent and human tissue samples and can also be used to quantify
      virus-cell attachment. 

PMID- 25978313
TI  - Anthropometric characteristics, physical fitness and motor coordination of 9 to
      11 year old children participating in a wide range of sports.
AB  - OBJECTIVES: The aim of this study was to investigate to what extent 9 to 11 year
      old children participating in a specific sport already exhibit a specific
      anthropometric, physical fitness and motor coordination profile, in line with the
      requirements of that particular sport. In addition, the profiles in children with
      a different training volume were compared and possible differences in training
      hours per week between children from a low, moderate, and high level of physical
      fitness and motor coordination were investigated. METHODS AND RESULTS: Data of
      620 children, 347 boys and 273 girls, who participated in the Flemish Sports
      Compass were used. Only the primary sport of each child was considered and six
      groups of sports (Ball sports, Dance, Gymnastics, Martial arts, Racquet sports
      and Swimming) were formed based on common characteristics. Measurements consisted
      of 17 tests. Independent T-tests and Mann-Whitney U-tests revealed few
      differences between the groups of sports and the discriminant analyses with the
      moderate and low active group did not show any significant results (p > .05).
      However, when discriminating among the high active children, a 85.2 % correct
      classification between six groups of sports was found (Wilks' Lambda = .137 and p
      < .001). Finally, children performing under average on the tests spent
      significantly fewer hours in sport per week (2.50 +/- 1.84 hours) compared to the
      children performing best (3.25 +/- 2.60 hours) (p = .016) and the children
      performing above average (2.90 +/- 1.96 hours) (p = .029) on physical fitness and
      motor coordination. DISCUSSION: The study showed that in general, children at a
      young age do not exhibit sport-specific characteristics, except in children with
      a high training volume. It is possible that on the one hand, children have not
      spent enough time yet in their sport to develop sport-specific qualities. On the
      other hand, it could be possible that they do not take individual qualities into
      account when choosing a sport.

PMID- 25978314
TI  - Selenium Supplementation in Fish: A Combined Chemical and Biomolecular Study to
      Understand Sel-Plex Assimilation and Impact on Selenoproteome Expression in
      Rainbow Trout (Oncorhynchus mykiss).
AB  - BACKGROUND: Selenium (Se) is an essential oligonutrient, as a component of
      several Se-containing proteins (selenoproteins), which exert important biological
      functions within an organism. In livestock, Se-enriched products have been
      proposed as dietary supplements to be included into functional feeds for animal
      preventive health care. To this end, it is important to understand the optimal
      range of concentrations for supplementation and how long it takes to be
      assimilated into the organism. METHODS: In this study, rainbow trout
      (Oncorhynchus mykiss) were fed a control diet containing 0.9 g Kg-1 Se or the
      same diet supplemented with a Se-Yeast product (Sel-Plex) to achieve Se
      concentrations ranging from 1.5-8.9 g Kg-1 for a period of ten weeks. Fish were
      sampled every two weeks for analysis. The kinetics of Se bioaccumulation and the
      effects on fish selenoprotein expression was determined in different tissues
      combining chemical and bimolecular techniques. RESULTS: The Sel-Plex enriched
      diets did not have any effect on survival and growth performance. The highest Se
      levels were found in liver and kidney followed by muscle and blood cells.
      Analysis of the Se concentration factor showed that liver is able to initially
      regulate the amount of Se accumulated. However, with higher dietary Se level (4.8
      and 8.9 g Kg-1) and longer times of exposure (10 weeks), regulation is
      ineffective and the Se tissue concentration increases. The expression of the
      selected trout selenoprotein transcripts showed an inverse correlation with Sel
      Plex augmentation in most cases. In liver, kidney and blood cells the highest up
      regulation of the trout selenoprotein genes was seen mostly in the group fed the
      diet enriched with the lowest concentration of Sel-Plex (0.5 g Kg-1) for 10
      weeks. CONCLUSION: Sel-Plex may represent an excellent Se supplement to deliver a
      high level of Se without provoking harm to the fish and to guarantee the maximal
      absorption of the element. According to our results, a dietary supplementation of
      Sel-Plex between 0.5 and 4 g Kg-1 may allow maximal benefits, whereas 8 g Kg-1
      may be excessive for the purpose of supplementation.

PMID- 25978315
TI  - Synthesis and characterization of a new Peptide prodrug of glucosamine with
      enhanced gut permeability.
AB  - The aim of this study was to synthesize a peptide prodrug of glucosamine (GlcN)
      with increased gut permeability through the gut peptide transporter 1 (PepT1).
      Glycine-Valine ester derivative of GlcN (GVG) was synthesised using solid phase
      synthesis followed by characterization and evaluation of its physicochemical and
      intestinal stability. In addition, GVG was evaluated for its ability to be
      biotransformed to GlcN in the liver homogenate. In vitro absorption of the new
      prodrug through everted rat gut was also assessed. GVG demonstrated significant
      and meaningful increased gut permeability as compared with GlcN. It showed
      favorable stability in the gut and a quick cleavage to GlcN after exposure to the
      liver homogenate. In conclusion, a novel prodrug of glucosamine with superior gut
      permeability compared to GlcN was developed and successfully tested in vitro. 

PMID- 25978316
TI  - Comparing glaucoma progression on 24-2 and 10-2 visual field examinations.
AB  - PURPOSE: To compare the rate of mean deviation (MD) change on 24-2 versus 10-2
      VFs in treated glaucomatous eyes with 5 or more examinations. METHODS: In a
      retrospective study, 24-2 and 10-2 VFs of 131 glaucoma patients (167 eyes) who
      had undergone at least 5 VFs examinations during their follow-up were analyzed.
      All these patients had VF defects both on 24-2 and 10-2 VFs. Rates of MD change
      were calculated using best linear unbiased predictions (BLUP). RESULTS: Median
      age, MD on 24-2 VF at baseline, number of VFs performed during follow-up and
      follow-up duration were 55 years, -16.9 dB, 9 and 9 years respectively. Median
      rate of MD change was significantly greater (p<0.001) on 10-2 VF (-0.26 dB/year;
      interquartile range [IQR]: -0.47, -0.11) compared to 24-2 VFs (-0.19 dB/year;
      IQR: -0.41, -0.03). Comparing the rates of MD change in eyes with different
      severities of VF loss (early [MD better than -6 dB], moderate [-6 dB to -12 dB],
      advanced [-12 to -20 dB] and severe [MD worse than -20 dB]) at baseline (based on
      the MD on 24-2 VF), median rate of MD change was comparable between 10-2 and 24-2
      VFs in mild (-0.45 dB/year vs. -0.40 dB/year, P = 0.42) and moderate (-0.32
      dB/year vs. -0.40 dB/year, P = 0.26) VF loss categories, while the same were
      significantly greater on 10-2 VFs in advanced (-0.28 dB/year vs. -0.21 dB/year, P
      = 0.04) and severe (-0.18 dB/year vs. -0.06 dB/year, P<0.001) VF loss categories.
      CONCLUSIONS: In patients with VF defects both on 24-2 and 10-2 VFs, evaluating
      the rate of MD change on 10-2 VFs may help in better estimation of glaucoma
      progression, especially so in eyes with advanced glaucoma at baseline.

PMID- 25978317
TI  - Interaction of cCMP with the cGK, cAK and MAPK Kinases in Murine Tissues.
AB  - cAMP and cGMP are well established second messengers that are essential for
      numerous (patho)physiological processes. These purine cyclic nucleotides activate
      cAK and cGK, respectively. Recently, the existence of cCMP was described, and a
      possible function for this cyclic nucleotide was investigated. It was postulated
      that cCMP plays a role as a second messenger. However, the functions regulated by
      cCMP are mostly unknown. To elucidate probable functions, cCMP-binding and 
      activated proteins were identified using different methods. We investigated the
      effect of cCMP on purified cyclic nucleotide-dependent protein kinases and lung
      and jejunum tissues of wild type (WT), cGKI-knockout (cGKI KO) and cGKII-knockout
      (cGKII KO) mice. The catalytic activity of protein kinases was measured by a
      (gamma-32P) ATP kinase assay. Cyclic nucleotide-dependent protein kinases (cAK,
      cGKI and cGKII) in WT tissue lysates were stimulated by cCMP. In contrast, there
      was no stimulation of phosphorylation in KO tissue lysates. Competitive binding
      assays identified cAK, cGKI, and cGKII as cCMP-binding proteins. An interaction
      between cCMP/MAPK and a protein-protein complex of MAPK/cGK were detected via
      cCMP affinity chromatography and co-immunoprecipitation, respectively. These
      complexes were abolished or reduced in jejunum tissues from cGKI KO or cGKII KO
      mice. In contrast, these complexes were observed in the lung tissues from WT,
      cGKI KO and cGKII KO mice. Moreover, cCMP was also able to stimulate the
      phosphorylation of MAPK. These results suggest that MAPK signaling is regulated
      by cGMP-dependent protein kinases upon activation by cCMP. Based on these
      results, we propose that additional cCMP-dependent protein kinases that are
      capable of modulating MAPK signaling could exist. Hence, cCMP could potentially
      act as a second messenger in the cAK/cGK and MAPK signaling pathways and play an
      important role in physiological processes of the jejunum and lung. 

PMID- 25978318
TI  - Early stress causes sex-specific, life-long changes in behaviour, levels of
      gonadal hormones, and gene expression in chickens.
AB  - Early stress can have long-lasting phenotypic effects. Previous research shows
      that male and female chickens differ in many behavioural aspects, and respond
      differently to chronic stress. The present experiment aimed to broadly
      characterize long-term sex differences in responses to brief events of stress
      experienced during the first weeks of life. Chicks from a commercial egg-laying
      hybrid were exposed to stress by inducing periods of social isolation during
      their first three weeks of life, followed by a broad behavioural, physiological
      and genomic characterization throughout life. Early stressed males, but not
      females, where more anxious in an open field-test, stayed shorter in tonic
      immobility and tended to have delayed sexual maturity, as shown by a tendency for
      lower levels of testosterone compared to controls. While early stressed females
      did not differ from non-stressed in fear and sexual maturation, they were more
      socially dominant than controls. The differential gene expression profile in
      hypothalamus was significantly correlated from 28 to 213 days of age in males,
      but not in females. In conclusion, early stress had a more pronounced long-term
      effect on male than on female chickens, as evidenced by behavioral, endocrine and
      genomic responses. This may either be attributed to inherent sex differences due
      to evolutionary causes, or possibly to different stress related selection
      pressures on the two sexes during commercial chicken breeding. 

PMID- 25978319
TI  - Integrating Taxonomic, Functional and Phylogenetic Beta Diversities: Interactive
      Effects with the Biome and Land Use across Taxa.
AB  - The spatial distribution of species, functional traits and phylogenetic
      relationships at both the regional and local scales provide complementary
      approaches to study patterns of biodiversity and help to untangle the mechanisms
      driving community assembly. Few studies have simultaneously considered the
      taxonomic (TBD), functional (FBD) and phylogenetic (PBD) facets of beta
      diversity. Here we analyze the associations between TBD, FBD, and PBD with the
      biome (representing different regional species pools) and land use, and
      investigate whether TBD, FBD and PBD were correlated. In the study design we
      considered two widely used indicator taxa (birds and ants) from two contrasting
      biomes (subtropical forest and grassland) and land uses (tree plantations and
      cropfields) in the southern Neotropics. Non-metric multidimensional scaling
      showed that taxonomic, functional and phylogenetic distances were associated to
      biome and land use; study sites grouped into four groups on the bi-dimensional
      space (cropfields in forest and grassland, and tree plantations in forest and
      grassland), and that was consistent across beta diversity facets and taxa. Mantel
      and PERMANOVA tests showed that TBD, FBD and PBD were positively correlated for
      both bird and ant assemblages; in general, partial correlations were also
      significant. Some of the functional traits considered here were conserved along
      phylogeny. Our results will contribute to the development of sound land use
      planning and beta diversity conservation. 

PMID- 25978320
TI  - MicroRNAs 9 and 370 Association with Biochemical Markers in T2D and CAD
      Complication of T2D.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non coding RNAs with essential roles, of
      which any alteration leads to several conditions. Their roles in diabetes (DM)
      and its vascular complications have not been completely assessed. AIM: to study
      the association of two miRNAs; 9 and 370, with biochemical parameters of type 2
      diabetic (T2D), dyslipidemia and coronary artery disease (CAD). SUBJECTS AND
      METHODS: Blood samples were taken from 200 subjects of both genders, in the
      Outpatient clinic of Al Qasr El-Einy teaching hospitals, in which levels of both
      miRNAs (using real time PCR) and routine parameters were measured. Subjects were
      divided over four groups, 50 in each group as follows; patients with T2D,
      patients with CAD, patients with T2D and CAD, and healthy control subjects. MAIN
      OUTCOME: miRNA 9 levels were expected to be over expressed in diabetic patients,
      while miRNA 370 levels were expected to be over expressed in those suffering from
      CAD and their association with CAD complication of T2D. RESULTS: miRNA 9 levels
      were significantly higher in T2D patients and T2D patients with CAD, (1.18+/
      0.07, and 1.31+/-0.08 respectively), while miRNA 370 levels were significantly
      higher in T2D patients, CAD patients, and T2D patients with CAD (0.59+/-0.05,
      1.00+/-0.05, and 1.20+/-0.06 respectively), compared to control group at p =
      0.000. In addition both miRNAs were still significantly associated with each
      other even after conducting multiple regression analysis. CONCLUSION: This study
      associates the possible role of miRNAs in the diagnosis/prognosis of CAD
      complication of T2D.

PMID- 25978321
TI  - Effect of training on the reliability of satiety evaluation and use of trained
      panellists to determine the satiety effect of dietary fibre: a randomised
      controlled trial.
AB  - BACKGROUND: The assessment of satiety effects on foods is commonly performed by
      untrained volunteers marking their perceived hunger or fullness on line scales,
      marked with pre-set descriptors. The lack of reproducibility of satiety
      measurement using this approach however results in the tool being unable to
      distinguish between foods that have small, but possibly important, differences in
      their satiety effects. An alternate approach is used in sensory evaluation;
      panellists can be trained in the correct use of the assessment line-scale and
      brought to consensus on the meanings of descriptors used for food quality
      attributes to improve the panel reliability. The effect of training on the
      reliability of a satiety panel has not previously been reported. METHOD: In a
      randomised controlled parallel intervention, the effect of training in the
      correct use of a satiety labelled magnitude scale (LMS) was assessed versus no
      training. The test-retest precision and reliability of two hour postprandial
      satiety evaluation after consumption of a standard breakfast was compared. The
      trained panel then compared the satiety effect of two breakfast meals containing
      either a viscous or a non-viscous dietary fibre in a crossover trial. RESULTS: A
      subgroup of the 23 panellists (n = 5) improved their test re-test precision after
      training. Panel satiety area under the curve, "after the training" intervention
      was significantly different to "before training" (p < 0.001). Reliability of the
      panel determined by intraclass correlation (ICC) of test and retest showed
      improved strength of the correlation from 0.70 pre-intervention to 0.95 post
      intervention. The trained "satiety expert panel" determined that a standard
      breakfast with 5g of viscous fibre gave significantly higher satiety than with 5g
      non-viscous fibre (area under curve (AUC) of 478.2, 334.4 respectively) (p <=
      0.002). CONCLUSION: Training reduced between panellist variability. The improved
      strength of test-retest ICC as a result of the training intervention suggests
      that training satiety panellists can improve the discriminating power of satiety
      evaluation.

PMID- 25978322
TI  - Insights into the Interactions of Fasciola hepatica Cathepsin L3 with a Substrate
      and Potential Novel Inhibitors through In Silico Approaches.
AB  - BACKGROUND: Fasciola hepatica is the causative agent of fascioliasis, a disease
      affecting grazing animals, causing economic losses in global agriculture and
      currently being an important human zoonosis. Overuse of chemotherapeutics against
      fascioliasis has increased the populations of drug resistant parasites. F.
      hepatica cathepsin L3 is a protease that plays important roles during the life
      cycle of fluke. Due to its particular collagenolytic activity it is considered an
      attractive target against the infective phase of F. hepatica.
      METHODOLOGY/PRINCIPAL FINDINGS: Starting with a three dimensional model of FhCL3
      we performed a structure-based design of novel inhibitors through a computational
      study that combined virtual screening, molecular dynamics simulations, and
      binding free energy (DeltaGbind) calculations. Virtual screening was carried out
      by docking inhibitors obtained from the MYBRIDGE-HitFinder database inside FhCL3
      and human cathepsin L substrate-binding sites. On the basis of dock-scores, five
      compounds were predicted as selective inhibitors of FhCL3. Molecular dynamic
      simulations were performed and, subsequently, an end-point method was employed to
      predict DeltaGbind values. Two compounds with the best DeltaGbind values (-10.68
      kcal/mol and -7.16 kcal/mol), comparable to that of the positive control (-10.55
      kcal/mol), were identified. A similar approach was followed to structurally and
      energetically characterize the interface of FhCL3 in complex with a peptidic
      substrate. Finally, through pair-wise and per-residue free energy decomposition
      we identified residues that are critical for the substrate/ligand binding and for
      the enzyme specificity. CONCLUSIONS/SIGNIFICANCE: The present study is the first
      computer-aided drug design approach against F. hepatica cathepsins. Here we
      predict the principal determinants of binding of FhCL3 in complex with a natural
      substrate by detailed energetic characterization of protease interaction surface.
      We also propose novel compounds as FhCL3 inhibitors. Overall, these results will
      foster the future rational design of new inhibitors against FhCL3, as well as
      other F. hepatica cathepsins.

PMID- 25978324
TI  - Correction: Impact of Age and Gender on the Prevalence and Prognostic Importance
      of the Metabolic Syndrome and Its Components in Europeans. The MORGAM Prospective
      Cohort Project.

PMID- 25978323
TI  - Repeated-measures implication of hepatocellular carcinoma biomarkers in living
      donor liver transplantation.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) and its recurrence are major problems
      in living donor liver transplantation (LDLT). Several biomarkers have been used
      to investigate this event. We conducted a prospective controlled study to
      determine the activities of the basic fibroblast growth factor (FGF-2), survivin,
      Ki67, endostatin, and vascular endothelial growth factor (VEGF) in different
      conditions before, early after, and late after LDLT with and without HCC
      recurrence. METHODS: Fifty patients with virus-related HCC who underwent LDLT
      were enrolled in this 2-year cross-sectional study. During the study period,
      recurrent HCC was identified in 9 patients (study group, n = 9) and 41 patients
      (control group, n = 41) had no recurrence after LDLT. The mean time to HCC
      recurrence was 587.11 +/- 398.64 days (range, 90-1352 days). Microvascular
      invasion (MVI) was found in 66.7% (6/9) of the recipients, as determined on
      pathological examination. The serum biomarkers were investigated by using enzyme
      linked immunosorbent assay at the different LDLT stages. RESULTS: The serum
      levels of the biomarkers significantly correlated with LDLT and HCC recurrence in
      the repeated-measures analysis (F = 31.676, P = 0.000). Significant differences
      were observed in the effects of all biomarkers (F = 85.313, P = 0.000) and the
      time to HCC recurrence after LDLT (F = 3.178, P = 0.046). The biomarkers, ordered
      by the observed power of the test for HCC recurrence after LDLT, were FGF-2
      (1.000) > survivin (0.999) > Ki67 (0.949) > endostatin (0.411) > VEGF (0.305).
      CONCLUSIONS: Different biomarker activities may be implicated in the pathogenesis
      of HCC recurrence after LDLT. Oncogenes may not exist in the new graft but may
      still be present in the peripheral blood. The timing of HCC recurrence and impact
      of MVI in the explanted liver requires confirmation in larger studies with a
      longer follow-up.

PMID- 25978325
TI  - Apply Protective Mechanical Ventilation in the Operating Room in an
      Individualized Approach to Perioperative Respiratory Care.

PMID- 25978326
TI  - Protective versus Conventional Ventilation for Surgery: A Systematic Review and
      Individual Patient Data Meta-analysis.
AB  - BACKGROUND: Recent studies show that intraoperative mechanical ventilation using
      low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs).
      The aim of this individual patient data meta-analysis is to evaluate the
      individual associations between VT size and positive end-expiratory pressure
      (PEEP) level and occurrence of PPC. METHODS: Randomized controlled trials
      comparing protective ventilation (low VT with or without high levels of PEEP) and
      conventional ventilation (high VT with low PEEP) in patients undergoing general
      surgery. The primary outcome was development of PPC. Predefined prognostic
      factors were tested using multivariate logistic regression. RESULTS: Fifteen
      randomized controlled trials were included (2,127 patients). There were 97 cases
      of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases
      in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative
      risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957
      patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63
      cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP
      levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose
      response relationship was found between the appearance of PPC and VT size (R2 =
      0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08).
      CONCLUSIONS: These data support the beneficial effects of ventilation with use of
      low VT in patients undergoing surgery. Further trials are necessary to define the
      role of intraoperative higher PEEP to prevent PPC during nonopen abdominal
      surgery.

PMID- 25978327
TI  - Decision Aid for Cigarette Smokers Scheduled for Elective Surgery.
AB  - BACKGROUND: Decision aids can increase patient involvement in decision-making
      about health care. The study goal was to develop and test a decision aid for use
      by clinicians in discussion options for changing smoking behavior before and
      after elective surgery. METHODS: In formative work, a decision aid was designed
      to facilitate patient-clinician discussion regarding three options: continue
      smoking, attempt a period of temporary abstinence, and attempt to quit smoking
      for good. A randomized, two-group pilot study was then conducted in smokers
      evaluated in preparation for elective surgery in a preoperative clinic to test
      the hypothesis that the decision aid would improve measures of decisional quality
      compared with usual care. RESULTS: The final decision aid consisted of three
      laminated cards. The front of each card included a colorful graphic describing
      each choice; the reverse including two to three pros and cons for each decision,
      a simple graphic illustrating the effects of smoking on the body, and a
      motivational phrase. In the randomized trial of 130 patients, the decision aid
      significantly (P < 0.05) improved measures of decisional quality and patient
      involvement in decision making (Cohen's d effect sizes of 0.76 and 1.20 for the
      Decisional Conflict Scale and Observing PatienT involvement In decisiON-making
      scale, respectively). However, the decision aid did not affect any aspect of
      perioperative smoking behavior, including the distribution of or adherence to
      choices. CONCLUSIONS: Although the use of a decision aid to facilitate clinician
      patient discussions regarding tobacco use around the time of surgery
      substantially improved measures of decisional quality, it alone did not change
      perioperative tobacco use behavior.

PMID- 25978328
TI  - Ion current rectification, limiting and overlimiting conductances in nanopores.
AB  - Previous reports on Poisson-Nernst-Planck (PNP) simulations of solid-state
      nanopores have focused on steady state behaviour under simplified boundary
      conditions. These are Neumann boundary conditions for the voltage at the pore
      walls, and in some cases also Donnan equilibrium boundary conditions for
      concentrations and voltages at both entrances of the nanopore. In this paper, we
      report time-dependent and steady state PNP simulations under less restrictive
      boundary conditions, including Neumann boundary conditions applied throughout the
      membrane relatively far away from the nanopore. We simulated ion currents through
      cylindrical and conical nanopores with several surface charge configurations,
      studying the spatial and temporal dependence of the currents contributed by each
      ion species. This revealed that, due to slow co-diffusion of oppositely charged
      ions, steady state is generally not reached in simulations or in practice.
      Furthermore, it is shown that ion concentration polarization is responsible for
      the observed limiting conductances and ion current rectification in nanopores
      with asymmetric surface charges or shapes. Hence, after more than a decade of
      collective research attempting to understand the nature of ion current
      rectification in solid-state nanopores, a relatively intuitive model is
      retrieved. Moreover, we measured and simulated current-voltage characteristics of
      rectifying silicon nitride nanopores presenting overlimiting conductances. The
      similarity between measurement and simulation shows that overlimiting
      conductances can result from the increased conductance of the electric double
      layer at the membrane surface at the depletion side due to voltage-induced
      polarization charges. The MATLAB source code of the simulation software is
      available via the website http://micr.vub.ac.be. 

PMID- 25978329
TI  - Detecting fragmentation extinction thresholds for forest understory plant species
      in peninsular Spain.
AB  - Ecological theory predicts that fragmentation aggravates the effects of habitat
      loss, yet empirical results show mixed evidences, which fail to support the
      theory instead reinforcing the primary importance of habitat loss. Fragmentation
      hypotheses have received much attention due to their potential implications for
      biodiversity conservation, however, animal studies have traditionally been their
      main focus. Here we assess variation in species sensitivity to forest amount and
      fragmentation and evaluate if fragmentation is related to extinction thresholds
      in forest understory herbs and ferns. Our expectation was that forest herbs would
      be more sensitive to fragmentation than ferns due to their lower dispersal
      capabilities. Using forest cover percentage and the proportion of this percentage
      occurring in the largest patch within UTM cells of 10-km resolution covering
      Peninsular Spain, we partitioned the effects of forest amount versus
      fragmentation and applied logistic regression to model occurrences of 16 species.
      For nine models showing robustness according to a set of quality criteria we
      subsequently defined two empirical fragmentation scenarios, minimum and maximum,
      and quantified species' sensitivity to forest contraction with no fragmentation,
      and to fragmentation under constant forest cover. We finally assessed how the
      extinction threshold of each species (the habitat amount below which it cannot
      persist) varies under no and maximum fragmentation. Consistent with their
      preference for forest habitats probability occurrences of all species decreased
      as forest cover contracted. On average, herbs did not show significant
      sensitivity to fragmentation whereas ferns were favored. In line with theory,
      fragmentation yielded higher extinction thresholds for two species. For the
      remaining species, fragmentation had either positive or non-significant effects.
      We interpret these differences as reflecting species-specific traits and conclude
      that although forest amount is of primary importance for the persistence of
      understory plants, to neglect the impact of fragmentation for some species can
      lead them to local extinction. 

PMID- 25978330
TI  - The Protecting Effect of Deoxyschisandrin and Schisandrin B on HaCaT Cells
      against UVB-Induced Damage.
AB  - Schisandra chinensis is a traditional Chinese medicine that has multiple
      biological activities, including antioxidant, anticancer, tonic, and anti-aging
      effects. Deoxyschisandrin (SA) and schisandrin B (SB), the two major lignans
      isolated from S. chinensis, exert high antioxidant activities in vitro and in
      vivo by scavenging free radicals, such as reactive oxygen species (ROS).
      Ultraviolet B-ray (UVB) radiation induces the production of ROS and DNA damage,
      which eventually leads to cell death by apoptosis. However, it is unknown whether
      SA or SB protects cells against UVB-induced cellular DNA damage. Our study showed
      that both SA and SB effectively protected HaCaT cells from UVB-induced cell death
      by antagonizing UVB-mediated production of ROS and induction of DNA damage. Our
      results showed that both SA and SB significantly prevented UVB-induced loss of
      cell viability using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
      bromide (MTT) assays. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays
      showed that the production of ROS following UVB exposure was inhibited by
      treatment with SA and SB. Moreover, SA and SB decreased the UVB-induced DNA
      damage in HaCaT cells by comet assays. In addition, SA and SB also prevented UVB
      induced cell apoptosis and the cleavage of caspase-3, caspase-8 and caspase-9. In
      a word, our results imply that the antioxidants SA and SB could protect cells
      from UVB-induced cell damage via scavenging ROS. 

PMID- 25978331
TI  - Correction: Abundant Genetic Overlap between Blood Lipids and Immune-Mediated
      Diseases Indicates Shared Molecular Genetic Mechanisms.

PMID- 25978332
TI  - Distal spike initiation zone location estimation by morphological simulation of
      ionic current filtering demonstrated in a novel model of an identified Drosophila
      motoneuron.
AB  - Studying ion channel currents generated distally from the recording site is
      difficult because of artifacts caused by poor space clamp and membrane filtering.
      A computational model can quantify artifact parameters for correction by
      simulating the currents only if their exact anatomical location is known. We
      propose that the same artifacts that confound current recordings can help
      pinpoint the source of those currents by providing a signature of the neuron's
      morphology. This method can improve the recording quality of currents initiated
      at the spike initiation zone (SIZ) that are often distal to the soma in
      invertebrate neurons. Drosophila being a valuable tool for characterizing ion
      currents, we estimated the SIZ location and quantified artifacts in an identified
      motoneuron, aCC/MN1-Ib, by constructing a novel multicompartmental model. Initial
      simulation of the measured biophysical channel properties in an isopotential
      Hodgkin-Huxley type neuron model partially replicated firing characteristics.
      Adding a second distal compartment, which contained spike-generating Na+ and K+
      currents, was sufficient to simulate aCC's in vivo activity signature. Matching
      this signature using a reconstructed morphology predicted that the SIZ is on
      aCC's primary axon, 70 MUm after the most distal dendritic branching point. From
      SIZ to soma, we observed and quantified selective morphological filtering of fast
      activating currents. Non-inactivating K+ currents are filtered ~3 times less and
      despite their large magnitude at the soma they could be as distal as Na+
      currents. The peak of transient component (NaT) of the voltage-activated Na+
      current is also filtered more than the magnitude of slower persistent component
      (NaP), which can contribute to seizures. The corrected NaP/NaT ratio explains the
      previously observed discrepancy when the same channel is expressed in different
      cells. In summary, we used an in vivo signature to estimate ion channel location
      and recording artifacts, which can be applied to other neurons. 

PMID- 25978335
TI  - Is a Single Entry Training Scheme for Intensive Care Medicine Both Inevitable and
      Desirable?
AB  - The development of Intensive Care Medicine as a recognizable branch of medicine
      has been underway for more than half a century, with delivery by a number of
      different service models. This delivery may be entirely by related medical
      specialties, such as anesthesiology or pulmonology; alternatively, it may be as a
      standalone-recognized specialty and frequently by a hybrid of these two extremes.
      A country may have a completely different delivery model from neighboring
      countries, and different models may exist within a single country. Debate about
      the most appropriate method of providing critical care services frequently
      centers around the training. However, an alternative perspective is that training
      regimes only follow on from another objective, namely to have Intensive Care
      Medicine represented in important forums by dedicated critical care physicians. A
      historical perspective of the development of critical care in two countries over
      a 40-year period is discussed, whereby a transition from a multiple specialty
      provision of critical care medicine to that of a single binational pathway
      occurred. The perceived advantages and disadvantages are outlined, offering
      insights into how possible future challenges in a highly complex medical
      specialty can be anticipated and strategies formulated. 

PMID- 25978333
TI  - Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in
      Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis
      in the Lupus-Prone NZBWF1 Mouse.
AB  - Genetic predisposition and environmental factors influence the development of
      human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has
      been etiologically linked to increased incidence of autoimmunity, including
      systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly
      understood. The purpose of this study was to test the hypothesis that early
      repeated short-term cSiO2 exposure will modulate both latency and severity of
      autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure
      to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency
      and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory
      responses in the lungs as evidenced by extensive perivascular and peribronchial
      lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and
      CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid
      tissue (ELT). In addition, there were elevated concentrations of immunoglobulins
      and the cytokines MCP-1, TNF-alpha and IL-6 in bronchoalveolar lavage fluid.
      cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of
      autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2
      induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1
      mouse corresponded closely to systemic inflammatory and autoimmune responses as
      well as the early initiation of pathological outcomes in the kidney. These
      findings suggest that following airway exposure to crystalline silica, in mice
      genetically prone to SLE, the lung serves as a platform for triggering systemic
      autoimmunity and glomerulonephritis. 

PMID- 25978334
TI  - Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly
      diagnosed patients with immune thrombocytopenia.
AB  - T cell abnormalities have been reported to play an important role in pathogenesis
      of immune thrombocytopenia (ITP) besides specific autoantibodies towards
      platelet. The aim of this study was to explore the clinical importance of T
      lymphocyte subsets in adult patients with newly diagnosed ITP before and after
      first-line treatment. Elderly ITP patients were also studied and we tried to
      analyze the relationships between these items and therapeutic outcomes. The
      patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids
      and therapeutic responses were evaluated. As a result, compared with the
      controls, absolute lymphocyte counts in ITP patients decreased significantly
      before treatment. After treatment, lymphocyte counts restored to control level
      regardless of their treatment outcomes. In addition, we observed increased IgG
      and CD19+ cell expression and decreased CD4+/CD8+ cell ratio in both whole ITP
      group and elderly group before treatment. After treatment, the increased IgG and
      CD19+ cell expression could be reduced in both respond and non-respond group
      regardless of patient age, while CD4+/CD8+ cell ratio could not be corrected in
      non-respond ITP patients. In non-respond ITP patients, increased CD8+ cell
      expression was noticed and could not be corrected by first-line treatment.
      Furthermore, even lower NK cell expression was found in non-respond elderly
      patients after treatment when compared with that in controls. Our findings
      suggest that ITP patients usually had less numbers of peripheral lymphocytes and
      patients with higher levels of CD8+ cells or lower levels of CD4+/CD8+ cell ratio
      were less likely to respond to first-line treatment. Lower levels of NK cells
      made therapies in elderly ITP patients even more difficult. 

PMID- 25978336
TI  - Cerebral Blood Flow Threshold Is Higher for Membrane Repolarization Than for
      Depolarization and Is Lowered by Intraischemic Hypothermia in Rats.
AB  - OBJECTIVES: To evaluate the cerebral blood flow thresholds for membrane
      depolarization and repolarization and the effect of brain hypothermia on the
      cerebral blood flow threshold for membrane repolarization. DESIGN: Prospective
      animal study. SETTING: Experimental laboratory in a university hospital.
      SUBJECTS: Male Sprague-Dawley rats (n = 40). INTERVENTIONS: Cerebral blood flow
      and membrane depolarization and repolarization in the cerebral cortex were
      simultaneously monitored by laser Doppler and extracellular potential,
      respectively. Following bilateral occlusion of the common carotid arteries,
      cerebral blood flow was decreased by draining blood at a rate of 2.5% of the
      control level/min until membrane depolarization was initiated. At 5 and 10
      minutes (Normothermia 5 and Normothermia 10 groups, respectively) after
      depolarization onset, cerebral blood flow was restored at the same rate until
      membrane repolarization was observed. In some animals, intraischemic brain
      hypothermia targeting 31 degrees C was initiated immediately after the onset of
      depolarization (Hypothermia 5 and Hypothermia 10 groups). MEASUREMENTS AND MAIN
      RESULTS: The cerebral blood flow threshold for repolarization (46.5% +/- 12%) was
      significantly higher than that for depolarization (18.9% +/- 4.8%; p < 0.01) in
      the Normothermia 5 group and was further increased to 61.5% +/- 14% (p < 0.01) in
      the Normothermia 10 group. With initiation of hypothermia, the cerebral blood
      flow threshold for membrane repolarization was suppressed to 33.8% +/- 10% in the
      Hypothermia 5 group (p < 0.01 vs Normothermia 5 group) and was unaltered by
      prolongation of ischemia (Hypothermia 10 group; 36.6% +/- 6%). CONCLUSIONS:
      Cerebral blood flow thresholds were significantly higher for repolarization than
      for depolarization and were further increased by prolonged ischemia.
      Intraischemic brain hypothermia decreased the repolarization threshold and
      abrogated the increase in the repolarization threshold caused by prolonged
      ischemia.

PMID- 25978338
TI  - Cardiovascular Critical Care: A Perceived Deficiency Among U.S. Trainees.
AB  - OBJECTIVE: Acute and chronic cardiovascular comorbidities are common among
      critically ill individuals. It is unclear if current critical care fellowship
      trainees feel adequately prepared to manage these conditions. DESIGN:
      Prospective, cross-sectional survey. PATIENTS OR SUBJECTS: Trainees enrolled in
      U.S. critical care training programs. SETTING: Accredited pulmonary/critical
      care, surgery/critical care, anesthesiology/critical care, and stand-alone
      critical care training programs. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: A 19-item survey assessing trainee confidence in the management of
      cardiac critical illness and the performance of cardiac-specific critical care
      interventions was constructed using Accreditation Council for Graduate Medical
      Education recommendations as a reference. After validation, the survey was
      electronically sent to all training programs for dissemination to their trainees.
      Confidence scores were measured on a Likert scale from 1 to 5. A total of 134
      completed surveys were analyzed. Overall, respondents reported lower confidence
      in managing cardiovascular compared with noncardiovascular diseases in the ICU
      (4.0 vs 4.6 out of 5). Likewise, they reported lower perceived competence in
      performing cardiovascular procedures specific to the ICU (2.9 vs 4.5 out of 5).
      The majority (88%) of those surveyed felt that they would benefit from increased
      didactic and clinical experience in the management of cardiovascular critical
      illness. CONCLUSIONS: Current critical care fellows may be unprepared to deal
      with the increasing prevalence of cardiovascular illness in the ICU. This
      potential educational gap warrants timely attention to ensure that future
      graduates have the requisite skills necessary to manage these critically ill
      patients and presents a unique opportunity to develop multidisciplinary
      partnerships for enhancing training.

PMID- 25978337
TI  - Dichotomous "Good Outcome" Indicates Mobility More Than Cognitive or Social
      Quality of Life.
AB  - OBJECTIVE: Worthwhile interventions for intracerebral hemorrhage or subarachnoid
      hemorrhage generally hinge on whether they improve the odds of good outcome.
      Although good outcome is correlated with mobility, correlations with other
      domains of health-related quality of life, such as cognitive function and social
      functioning, are not well described. We tested the hypothesis that good outcome
      is more closely associated with mobility than other domains. DESIGN: We defined
      "good outcome" as 0 through 3 (independent ambulation or better) versus 4 through
      5 (dependent) on the modified Rankin Scale at 1, 3, and 12 months. We
      simultaneously assessed the modified Rankin Scale and health-related quality of
      life using web-based computer adaptive testing in the domains of mobility,
      cognitive function (executive function and general concerns), and satisfaction
      with social roles and activities. We compared the area under the curve between
      different health-related quality of life domains. SETTING: Neurologic ICU with
      web-based follow-up. PATIENTS: One hundred fourteen patients with subarachnoid
      hemorrhage or intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENT AND MAIN
      RESULTS: We longitudinally followed 114 survivors with data at 1 month, 62
      patients at 3 months, and 58 patients at 12 months. At 1 month, area under the
      curve was highest for mobility (0.957; 95% CI, 0.904-0.98), higher than cognitive
      function-general concerns (0.819; 95% CI, 0.715-0.888; p = 0.003 compared with
      mobility), satisfaction with social roles and activities (0.85; 95% CI, 0.753
      0.911; p = 0.01 compared with mobility), and cognitive function-executive
      function (0.879; 95% CI, 0.782-0.935; p = 0.058 compared with mobility). Optimal
      specificity and sensitivity for receiver operating characteristic analysis were
      approximately 1.5 SD below the U.S. population mean. CONCLUSIONS: Health-related
      quality of life assessments reliably distinguished between good and poor outcomes
      as determined by the modified Rankin Scale. Good outcome indicated health-related
      quality of life about 1.5 SD below the U.S. population mean. Associations were
      weaker for cognitive function and social function than mobility.

PMID- 25978339
TI  - Urgent Ultrasound-Guided Bilateral Stellate Ganglion Blocks in a Patient With
      Medically Refractory Ventricular Arrhythmias.
AB  - OBJECTIVES: To describe the successful treatment of medically refractory
      ventricular arrhythmias in the ICU with ultrasound-guided bilateral stellate
      ganglion blocks. DATA SOURCES: The data were gathered from the medical record.
      STUDY SELECTION: This case was selected as it describes the use of ultrasound in
      the successful termination of a recurrent, malignant arrhythmia, rather than
      fluoroscopy, to perform bilateral stellate ganglion blocks at the patient's
      bedside in the ICU. DATA EXTRACTION: The data were extracted from the medical
      record. DATA SYNTHESIS: The data were synthesized from the patient's medical
      record. CONCLUSIONS: Performance of stellate ganglion blocks at the bedside in
      the ICU is feasible for patients who are suffering from refractory ventricular
      arrhythmias. This potentially life-saving block can be performed using ultrasound
      guidance, sparing the patient transport to a fluoroscopy suite.

PMID- 25978340
TI  - Ventilator-Associated Events: Prevalence, Outcome, and Relationship With
      Ventilator-Associated Pneumonia.
AB  - OBJECTIVES: Centers for Disease Control and Prevention built up new surveillance
      paradigms for the patients on mechanical ventilation and the ventilator
      associated events, comprising ventilator-associated conditions and infection
      related ventilator-associated complications. We assess 1) the current
      epidemiology of ventilator-associated event, 2) the relationship between
      ventilator-associated event and ventilator-associated pneumonia, and 3) the
      impact of ventilator-associated event on antimicrobials consumption and
      mechanical ventilation duration. DESIGN: Inception cohort study from the
      longitudinal prospective French multicenter OUTCOMEREA database (1996-2012).
      PATIENTS: Patients on mechanical ventilation for greater than or equal to 5
      consecutive days were classified as to the presence of a ventilator-associated
      event episode, using slightly modified Centers for Disease Control and Prevention
      definitions. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among the 3,028
      patients, 2,331 patients (77%) had at least one ventilator-associated condition,
      and 869 patients (29%) had one infection-related ventilator-associated
      complication episode. Multiple causes, or the lack of identified cause, were
      frequent. The leading causes associated with ventilator-associated condition and
      infection-related ventilator-associated complication were nosocomial infections
      (27.3% and 43.8%), including ventilator-associated pneumonia (14.5% and 27.6%).
      Sensitivity and specificity of diagnosing ventilator-associated pneumonia were
      0.92 and 0.28 for ventilator-associated condition and 0.67 and 0.75 for infection
      related ventilator-associated complication, respectively. A good correlation was
      observed between ventilator-associated condition and infection-related ventilator
      associated complication episodes, and ventilator-associated pneumonia occurrence:
      R = 0.69 and 0.82 (p < 0.0001). The median number of days alive without
      antibiotics and mechanical ventilation at day 28 was significantly higher in
      patients without any ventilator-associated event (p < 0.05). Ventilator
      associated condition and infection-related ventilator-associated complication
      rates were closely correlated with antibiotic use within each ICU: R = 0.987 and
      0.99, respectively (p < 0.0001). CONCLUSIONS: Ventilator-associated event is very
      common in a population at risk and more importantly highly related to
      antimicrobial consumption and may serve as surrogate quality indicator for
      improvement programs.

PMID- 25978341
TI  - Interprofessional team meetings: Opportunities for informal interprofessional
      learning.
AB  - This study explores the potential for workplace interprofessional learning,
      specifically the learning that occurs between health professionals as part of
      their attendance at their regular interprofessional team meetings. While most
      interprofessional learning research to date has focused on formal structured
      education programs, this study adds to our understanding of the complexities of
      the learning processes occurring between health professionals as part of everyday
      practice. Through observations of team meetings and semi-structured interviews,
      we found that the interprofessional team meeting provided a practical, time
      efficient, and relevant means for interprofessional learning, resulting in
      perceived benefits to individuals, teams, and patients. The learning process,
      however, was influenced by members' conceptions of learning, participation within
      the meeting, and medical presence. This study provides a basis for further
      research to assist health professionals capitalize on informal learning
      opportunities within the interprofessional meeting. 

PMID- 25978343
TI  - Calling Behavior of Male Acheta domesticus Crickets Infected with Paragordius
      varius (Nematomorpha: Gordiida).
AB  - It is well established that parasites in the phylum Nematomorpha induce suicide
      behavior of their insect hosts to bring adult worms to the appropriate habitat
      for emergence. It is not well established, however, whether other nematomorph
      induced behavioral alterations occur before worm emergence. The purpose of our
      study was to evaluate the effect of the nematomorph Paragordius varius on the
      calling behavior of the male house cricket Acheta domesticus . We hypothesized
      that cricket calling, an energetically expensive and risky behavior, would be a
      potential target for nematomorph-induced behavioral alterations. We assessed if
      and how infection with P. varius affects A. domesticus calling behavior and
      whether the presence of wings at time of exposure to P. varius influenced changes
      in calling behavior. We recorded the calling behavior of male A. domesticus over
      the course of their infection after exposure to P. various before or after wing
      development. Additionally, we assessed whether winged crickets were "callers" or
      "noncallers" before exposure. We found that regardless of cricket developmental
      stage (or age) at time of infection, infected crickets spent significantly less
      time calling than their uninfected counterparts but only during the later stages
      of infection. Developmental stage at infection did affect whether crickets became
      callers: when infected before wing development significantly more uninfected
      crickets initiated calling; there was no difference between infected and
      uninfected crickets when infected as winged adults. Infection was a factor in
      whether callers stopped calling, with more infected crickets ceasing to call than
      uninfected crickets. This is the first study to show that infection with
      nematomorphs affects calling behavior of their insect host. Cricket calling
      behavior is immensely complex and although it was difficult to elucidate the
      adaptive nature of these parasite-induced behavioral changes, this study lays the
      groundwork for future studies to begin teasing out the factors that will help
      make the determination between side effect of infection or parasite/host
      adaptation. 

PMID- 25978342
TI  - Correlates of Incident Cognitive Impairment in the REasons for Geographic and
      Racial Differences in Stroke (REGARDS) Study.
AB  - OBJECTIVE: To identify approximately 500 cases of incident cognitive impairment
      (ICI) in a large, national sample adapting an existing cognitive test-based case
      definition and to examine relationships of vascular risk factors with ICI.
      METHOD: Participants were from the REGARDS study, a national sample of 30,239
      African-American and White Americans. Participants included in this analysis had
      normal cognitive screening and no history of stroke at baseline, and at least one
      follow-up cognitive assessment with a three-test battery (TTB). Regression-based
      norms were applied to TTB scores to identify cases of ICI. Logistic regression
      was used to model associations with baseline vascular risk factors. RESULTS: We
      identified 495 participants with ICI of 17,630 eligible participants. In
      multivariable modeling, income (OR 1.83 CI 1.27,2.62), stroke belt residence (OR
      1.45 CI 1.18,1.78), history of transient ischemic attack (OR 1.90 CI 1.29,2.81),
      coronary artery disease(OR 1.32 CI 1.02,1.70), diabetes (OR 1.48 CI 1.17,1.87),
      obesity (OR 1.40 CI 1.05,1.86), and incident stroke (OR 2.73 CI 1.52,4.90) were
      associated with ICI. CONCLUSIONS: We adapted a previously validated cognitive
      test-based case definition to identify cases of ICI. Many previously identified
      risk factors were associated with ICI, supporting the criterion-related validity
      of our definition.

PMID- 25978344
TI  - Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding
      protein and high-mobility group box protein 1 in metabolic syndrome.
AB  - OBJECTIVE: Adipose Tissue (AT) dysregulation contributes to the pro-inflammatory
      state and insulin resistance of Metabolic Syndrome (MetS). We examined AT
      secretion of the hepatokine, Fetuin-A, LBP, sCD14 and HMGB-1, and toll-like
      receptor 2 and 4 protein levels in MetS and controls. DESIGN AND METHODS:
      Secreted levels of Fetuin-A, LBP, HMGB-1 and sCD14 and TLR2 and TLR4 protein in
      AT of controls and MetS patients were assayed. Also mRNA and protein for Fetuin
      A, LBP, sCD14 and HMGB-1 were studied in subcutaneous fat depot of mice and
      during adipocyte differentiation. RESULTS: Secretion of Fetuin-A, LBP and HMGB-1
      from AT were significantly increased in MetS (n = 28) compared to controls (n =
      25), even after adjustment for adiposity. There were no significant differences
      in sCD14. Both LBP and Fetuin-A correlated significantly with HOMA-IR and
      increased significantly with increasing features of MetS. There was a significant
      increase in AT TLR2 and TLR4 protein in MetS compared to controls. Expression of
      Fetuin-A and LBP were significantly higher in subcutaneous white adipose tissue
      of HFD fed mice as well as in ob/ob mice compared to C57BL6/J control mice (n = 6
      per group). Additionally mRNA and protein levels of FetA, LBP and HMGB-1
      increased during differentiation of 3T3-L1 adipocytes. CONCLUSIONS: We make the
      novel observation of increased secretion of Fetuin A, LBP and HMGB-1 from AT and
      hypothesize that these engage TLRs in AT and other tissues contributing to the
      pro-inflammatory state and insulin resistance of MetS.

PMID- 25978345
TI  - A national fine spatial scale land-use regression model for ozone.
AB  - Uncertainty about health effects of long-term ozone exposure remains. Land use
      regression (LUR) models have been used successfully for modeling fine scale
      spatial variation of primary pollutants but very limited for ozone. Our objective
      was to assess the feasibility of developing a national LUR model for ozone at a
      fine spatial scale. Ozone concentrations were measured with passive samplers at
      90 locations across the Netherlands (19 regional background, 36 urban background,
      35 traffic). All sites were measured simultaneously during four 2-weekly
      campaigns spread over the seasons. LUR models were developed for the summer
      average as the primary exposure and annual average using predictor variables
      obtained with Geographic Information Systems. Summer average ozone concentrations
      varied between 32 and 61 ug/m(3). Ozone concentrations at traffic sites were on
      average 9 ug/m(3) lower compared to regional background sites. Ozone correlated
      highly negatively with nitrogen dioxide and moderately with fine particles. A LUR
      model including small-scale traffic, large-scale address density, urban green and
      a region indicator explained 71% of the spatial variation in summer average ozone
      concentrations. Land use regression modeling is a promising method to assess
      ozone spatial variation, but the high correlation with NO2 limits application in
      epidemiology.

PMID- 25978346
TI  - A mechanistic investigation of the ruthenium porphyrin catalysed aziridination of
      olefins by aryl azides.
AB  - A mechanism for the aziridination of olefins by aryl azides (ArN3), promoted by
      ruthenium(ii) porphyrin complexes, is proposed on the basis of kinetic and
      theoretical studies. All the recorded data support the involvement of a mono
      imido ruthenium complex as the active intermediate in the transfer of the nitrene
      moiety "ArN" to the olefin. The selectivity of the aziridination vs. the
      uncatalysed triazoline formation can be enhanced by fine-tuning the electronic
      features of the porphyrin ligand and the olefin/azide catalytic ratio. The DFT
      study highlights the importance of an accessible triplet ground state of the
      intermediate ruthenium mono-imido complex to allow the evolution of the
      aziridination process. 

PMID- 25978347
TI  - Distribution of transient receptor potential melastatin-8-containing nerve fibers
      in rat oral and craniofacial structures.
AB  - The transient receptor potential melastatin-8 (TRPM8) is a cold and menthol
      receptor located in the sensory ganglia. Immunohistochemistry for TRPM8 was
      performed on oral and craniofacial structures of the rat. TRPM8-immunoreactive (
      IR) nerve fibers were detected in the oral mucous membrane. In the gingiva, TRPM8
      IR nerve fibers were abundant beneath and within crestal and outer epithelia.
      Such nerve fibers were also common beneath and within taste buds in the incisive
      papilla. In addition, TRPM8-immunoreactivity was expressed by some taste bud
      cells in the papilla. Lips, periodontal ligaments and salivary glands as well as
      masticatory muscles and temporomandibular joints were mostly devoid of TRPM8-IR
      nerve fibers. A double immunofluorescence study indicated different distribution
      patterns of nerve fibers containing TRPM8 and calcitonin gene-related peptide in
      oral and craniofacial tissues. Retrograde tracing method also indicated that
      TRPM8-IR nerve fibers in the gingiva and incisive papilla originate from small
      sensory neurons in the trigeminal ganglion. TRPM8 may be associated with cool,
      cold nociceptive (<around 25 degrees C) and chemoreceptive transmission in the
      oral mucosa. 

PMID- 25978348
TI  - Electrospun polymer nanofibres as solid-phase extraction sorbents for extraction
      and quantification of microcystins.
AB  - Electrospun polymer nanofibres were used as novel solid-phase extraction (SPE)
      sorbents to extract and quantify the microcystins (MCs) including microcystin-RR
      (MC-RR) and microcystin-LR (MC-LR) from in-suit water samples. The parameters
      that influenced the extraction efficiency were studied, including the amount of
      nanofibre, eluted solvent, eluted volume, pH, and the water sample volume. Under
      optimized conditions, a linear response for MC-RR and MC-LR over the range of
      0.25-4 ug/L was achieved with r(2) values of 0.998 and 0.997, respectively. The
      extraction recovery of MC-RR and MC-LR was 97-102% and 98-100%, respectively,
      when the MC concentration was 0.25-4 ug/L. When their concentrations ranged from
      0.05  to 0.25 ug/L, the MCs could be detected with high accuracy by the nanofibre
      SPE sorbent combined with nitrogen gas. Due to its simplicity, environment
      friendliness, high efficiency, reusability, and sensitivity, the electrospun
      polymer nanofibre can be applied as a novel SPE sorbent to extract and detect the
      MCs from in-suit water samples. 

PMID- 25978349
TI  - On the Maintenance of Human Heat Balance during Cold and Warm Fluid Ingestion.

PMID- 25978350
TI  - Response.

PMID- 25978351
TI  - Contribution of coated humic acids calculated through their surface coverage on
      nano iron oxides for ofloxacin and norfloxacin sorption.
AB  - Sorption of organic contaminants on organo-mineral complexes has been
      investigated extensively, but the sorption contribution of mineral particles was
      not properly addressed before calculating KOC, especially for ionic organic
      contaminants. We measured the surface coverage of a humic acid (HA) on nano iron
      oxides (n-Fe2O3) in a series of synthesized organo-mineral complexes. The
      contribution of the coated HA to ofloxacin (OFL) and norfloxacin (NOR) sorption
      in HA-n-Fe2O3 complexes was over 80% of the total sorption with the surface
      coverage of 36% and fOC of 1.6%. All the coated HA showed higher sorption to NOR
      and OFL in comparison to the original HA, suggesting HA fractionation and/or
      physical re-conformation during organo-mineral complex formation. The decreased
      KOC with multilayer coating may suggest the importance of site-specific
      interactions for OFL sorption, while the increased KOC with multilayer coating
      may suggest the importance of partitioning in hydrophobic region for NOR
      sorption. 

PMID- 25978352
TI  - Commuter exposure to particulate matter and particle-bound PAHs in three
      transportation modes in Beijing, China.
AB  - Exposure to fine and ultrafine particles as well as particulate polycyclic
      aromatic hydrocarbons (PAHs) by commuters in three transportation modes (walking,
      subway and bus) were examined in December 2011 in Beijing, China. During the
      study period, real-time measured median PM2.5 mass concentration (PMC) for
      walking, riding buses and taking the subway were 26.7, 32.9 and 56.9 MUg m(-3),
      respectively, and particle number concentrations (PNC) were 1.1 * 10(4), 1.0 *
      10(4) and 2.2 * 10(4) cm(-3). Commuters were exposed to higher PNC in air
      conditioned buses and aboveground-railway, but higher PMC in underground-subway
      compared to aboveground-railway. PNC in roadway modes (bus and walking) peaked at
      noon, but was lower during traffic rush hours, negatively correlated with PMC.
      Toxic potential of particulate-PAHs estimated based on benzo(a)pyrene toxic
      equivalents (BaP TEQs) showed that walking pedestrians were subjected to higher
      BaP TEQs than bus (2.7-fold) and subway (3.6-fold) commuters, though the highest
      PMC and PNC were observed in subway. 

PMID- 25978353
TI  - Counteracting foaming caused by lipids or proteins in biogas reactors using
      rapeseed oil or oleic acid as antifoaming agents.
AB  - Foaming is one of the major operational problems in biogas plants, and dealing
      with foaming incidents is still based on empirical practices. Various types of
      antifoams are used arbitrarily to combat foaming in biogas plants, but without
      any scientific support this action can lead to serious deterioration of the
      methanogenic process. Many commercial antifoams are derivatives of fatty acids or
      oils. However, it is well known that lipids can induce foaming in manure based
      biogas plants. This study aimed to elucidate the effect of rapeseed oil and oleic
      acid on foam reduction and process performance in biogas reactors fed with
      protein or lipid rich substrates. The results showed that both antifoams
      efficiently suppressed foaming. Moreover rapeseed oil resulted in stimulation of
      the biogas production. Finally, it was reckoned that the chemical structure of
      lipids, and more specifically their carboxylic ends, is responsible for their
      foam promoting or foam counteracting behaviour. Thus, it was concluded that the
      fatty acids and oils could suppress foaming, while salt of fatty acids could
      generate foam. 

PMID- 25978354
TI  - Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the
      VEGFR2/Src/FAK Pathway.
AB  - Inhibition of VEGFR2 activity has been proposed as an important strategy for the
      clinical treatment of hepatocellular carcinoma (HCC). In this study, we
      identified corosolic acid (CA), which exists in the root of Actinidia chinensis,
      as having a significant anti-cancer effect on HCC cells. We found that CA
      inhibits VEGFR2 kinase activity by directly interacting with the ATP binding
      pocket. CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, subsequently decreasing
      F-actin formation and migratory activity in vitro. In an in vivo model, CA
      exhibited an effective dose (5 mg/kg/day) on tumor growth. We further demonstrate
      that CA has a synergistic effect with sorafenib within a wide range of
      concentrations. In conclusion, this research elucidates the effects and molecular
      mechanism for CA on HCC cells and suggests that CA could be a therapeutic or
      adjuvant strategy for patients with aggressive HCC. 

PMID- 25978355
TI  - Potential Transmission Pathways of Streptococcus gallolyticus subsp.
      gallolyticus.
AB  - Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus subsp.
      gallolyticus), a member of group D streptococci, is an inhabitant of the animal
      and human gastrointestinal tract. Furthermore, it is a facultative pathogen which
      causes e.g. endocarditis, septicemia and mastitis. S. gallolyticus subsp.
      gallolyticus may be transmitted either directly or indirectly between animals and
      humans. However, the transmission routes are an unsolved issue. In this study, we
      present systematic analyses of an S. gallolyticus subsp. gallolyticus isolate of
      an infective endocarditis patient in relation to isolates of his laying hen
      flock. Isolates from pooled droppings of laying hens, pooled dust samples and
      human blood culture were characterized by using multilocus sequence typing (MLST)
      and DNA fingerprinting. MLST revealed the same allelic profile of isolates from
      the human blood culture and from the droppings of laying hens. In addition, these
      isolates showed clonal identity regarding a similar DNA fingerprinting pattern.
      For the first time, we received a hint that transmission of S. gallolyticus
      subsp. gallolyticus between poultry and humans may occur. This raises the
      question about the zoonotic potential of isolates from poultry and should be
      considered in future studies. 

PMID- 25978356
TI  - A large and deep root system underlies high nitrogen-use efficiency in maize
      production.
AB  - Excessive N fertilization results in low N-use efficiency (NUE) without any yield
      benefits and can have profound, long-term environmental consequences including
      soil acidification, N leaching and increased production of greenhouse gases.
      Improving NUE in crop production has been a longstanding, worldwide challenge. A
      crucial strategy to improve NUE is to enhance N uptake by roots. Taking maize as
      a model crop, we have compared root dry weight (RDW), root/shoot biomass ratio
      (R/S), and NUE of maize grown in the field in China and in western countries
      using data from 106 studies published since 1959. Detailed analysis revealed that
      the differences in the RDW and R/S of maize at silking in China and the western
      countries were not derived from variations in climate, geography, and stress
      factors. Instead, NUE was positively correlated with R/S and RDW; R/S and NUE of
      maize varieties grown in western countries were significantly greater than those
      grown in China. We then testified this conclusion by conducting field trials with
      representative maize hybrids in China (ZD958 and XY335) and the US (P32D79). We
      found that US P32D79 had a better root architecture for increased N uptake and
      removed more mineral N than Chinese cultivars from the 0-60 cm soil profile.
      Reported data and our field results demonstrate that a large and deep root, with
      an appropriate architecture and higher stress tolerance (higher plant density,
      drought and N deficiency), underlies high NUE in maize production. We recommend
      breeding for these traits to reduce the N-fertilizer use and thus N-leaching in
      maize production and paying more attention to increase tolerance to stresses in
      China. 

PMID- 25978357
TI  - Immunostimulatory Effects Triggered by Enterococcus faecalis CECT7121 Probiotic
      Strain Involve Activation of Dendritic Cells and Interferon-Gamma Production.
AB  - Probiotics can modulate the immune system, conferring beneficial effects on the
      host. Understanding how these microorganisms contribute to improve the health
      status is still a challenge. Previously, we have demonstrated that Enterococcus
      faecalis CECT7121 implants itself and persists in the murine gastrointestinal
      tract, and enhances and skews the profile of cytokines towards the Th1 phenotype
      in several biological models. Given the importance of dendritic cells (DCs) in
      the orchestration of immunity, the aim of this work was to elucidate the
      influence of E. faecalis CECT7121 on DCs and the outcome of the immune responses.
      In this work we show that E. faecalis CECT7121 induces a strong dose-dependent
      activation of DCs and secretion of high levels of IL-12, IL-6, TNFalpha, and IL
      10. This stimulation is dependent on TLR signaling, and skews the activation of T
      cells towards the production of IFNgamma. The influence of this activation in the
      establishment of Th responses in vivo shows the accumulation of specific IFNgamma
      producing cells. Our findings indicate that the activation exerted by E. faecalis
      CECT7121 on DCs and its consequence on the cellular adaptive immune response may
      have broad therapeutic implications in immunomodulation. 

PMID- 25978358
TI  - A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed
      Cells during Development.
AB  - Eukaryotic cells have evolved signaling pathways that help to restore cellular
      homeostasis in response to various physiological or pathological conditions. ATF4
      is a transcription factor whose mRNA translation is stimulated in response to
      stress-activated eIF2alpha kinases. Established conditions that activate
      eIF2alpha phosphorylation and ATF4 translation include excessive stress in the
      endoplasmic reticulum (ER) and amino acid deprivation. ATF4 is activated through
      a unique translational activation mechanism that involves multiple upstream open
      reading frames (uORFs) in the 5'-untranslated region (UTR), which is conserved
      from yeast to mammals. Taking advantage of this, we developed a translational
      activation reporter of ATF4 in Drosophila, in which the dsRed reporter coding
      sequence was placed downstream of the Drosophila ATF4 5' UTR. This reporter
      remained inactive in most tissues under normal conditions, but showed dsRed
      expression when starved, or when challenged with conditions that imposed ER
      stress. In normally developing flies, a small number of cell types showed
      reporter expression even without exogenous stress, which included the salivary
      gland, gut, the male reproductive organ, and the photoreceptor cells, suggestive
      of inherent stress during the normal development of these cell types. These
      results establish a new tool to study ATF4-mediated stress response in Drosophila
      development and disease. 

PMID- 25978359
TI  - The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel
      Diseases (IBDs).
AB  - BACKGROUND AND AIMS: Immune semaphorins are a large family of proteins involved
      in the pathogenesis of inflammatory diseases through the regulation of immune
      homeostasis and tissue inflammation. We aim to assess the possible involvement of
      semaphorin3A (sema3A) and 4A (sema4A) in peripheral immune responses and bowel
      tissue inflammation of patients suffering from Crohn's disease (CD) and
      ulcerative colitis (UC). PATIENTS AND METHODS: Twenty-seven CD patients and 10 UC
      patients were studied and compared to 10 patients followed for acute
      diverticulitis (disease control) and 12 healthy individuals. All were evaluated
      for sema3A expression on T regulatory cells (Tregs), serum levels of sema3A and
      sema4A, and tissue expression of sema3A and sema4A in bowel biopsies. RESULTS:
      The percentage (%) of T regulatory cells (Tregs) expressing sema3A in patients
      with active CD (64.5% +/- 14.49%) and active UC (49.8% +/- 16.45%) was
      significantly lower when compared to that of healthy controls (88.7% +/- 3.6%, p<
      0.001 and p< 0.0001, respectively). This expression was seen to be in negative
      correlation with CD activity. Serum levels of Sema4A were significantly lower in
      patients with CD and UC when compared to that of controls (5.69 +/- 1 .48 ng?ml
      for CD, 5.26 +/- 1.23 ng/ml for UC patients vs 9.74 +/- 2.73 ng/ml for normal
      controls, P<0.001). Sema4A was highly expressed in lymphocytes of the lamina
      propria of CD and UC patients but absent in patients with diverticulitis or in
      normal individuals. CONCLUSIONS: Altered % of Tregs expressing sema3A in patients
      with inflammatory bowel diseases (IBD) is partially responsible for their failure
      in preventing CD4+ effector T cell induced inflammation in IBD in peripheral
      blood. The increased expression of sema4A in bowel biopsies from CD and UC
      patients is suggestive of its central role in regulating local tissue
      inflammation in the bowel.

PMID- 25978360
TI  - The role of the organization structure in the diffusion of innovations.
AB  - Diffusion and adoption of innovations is a topic of increasing interest in
      economics, market research, and sociology. In this paper we investigate, through
      an agent based model, the dynamics of adoption of innovative proposals in
      different kinds of structures. We show that community structure plays an
      important role on the innovation diffusion, so that proposals are more likely to
      be accepted in homogeneous organizations. In addition, we show that the learning
      process of innovative technologies enhances their diffusion, thus resulting in an
      important ingredient when heterogeneous networks are considered. We also show
      that social pressure blocks the adoption process whatever the structure of the
      organization. These results may help to understand how different factors
      influence the diffusion and acceptance of innovative proposals in different
      communities and organizations. 

PMID- 25978361
TI  - Simvastatin and Benznidazole-Mediated Prevention of Trypanosoma cruzi-Induced
      Endothelial Activation: Role of 15-epi-lipoxin A4 in the Action of Simvastatin.
AB  - Trypanosoma cruzi is the causal agent of Chagas Disease that is endemic in Latin
      American, afflicting more than ten million people approximately. This disease has
      two phases, acute and chronic. The acute phase is often asymptomatic, but with
      time it progresses to the chronic phase, affecting the heart and gastrointestinal
      tract and can be lethal. Chronic Chagas cardiomyopathy involves an inflammatory
      vasculopathy. Endothelial activation during Chagas disease entails the expression
      of cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1
      (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) through a mechanism
      involving NF-kappaB activation. Currently, specific trypanocidal therapy remains
      on benznidazole, although new triazole derivatives are promising. A novel
      strategy is proposed that aims at some pathophysiological processes to facilitate
      current antiparasitic therapy, decreasing treatment length or doses and slowing
      disease progress. Simvastatin has anti-inflammatory actions, including
      improvement of endothelial function, by inducing a novel pro-resolving lipid, the
      5-lypoxygenase derivative 15-epi-lipoxin A4 (15-epi-LXA4), which belongs to
      aspirin-triggered lipoxins. Herein, we propose modifying endothelial activation
      with simvastatin or benznidazole and evaluate the pathways involved, including
      induction of 15-epi-LXA4. The effect of 5 MUM simvastatin or 20 MUM benznidazole
      upon endothelial activation was assessed in EA.hy926 or HUVEC cells, by E
      selectin, ICAM-1 and VCAM-1 expression. 15-epi-LXA4 production and the
      relationship of both drugs with the NFkappaB pathway, as measured by IKK-IKB
      phosphorylation and nuclear migration of p65 protein was also assayed. Both drugs
      were administered to cell cultures 16 hours before the infection with T. cruzi
      parasites. Indeed, 5 MUM simvastatin as well as 20 MUM benznidazole prevented the
      increase in E-selectin, ICAM-1 and VCAM-1 expression in T. cruzi-infected
      endothelial cells by decreasing the NF-kappaB pathway. In conclusion, Simvastatin
      and benznidazole prevent endothelial activation induced by T. cruzi infection,
      and the effect of simvastatin is mediated by the inhibition of the NFkappaB
      pathway by inducing 15-epi-LXA4 production. 

PMID- 25978362
TI  - Identification of Rv3852 as an Agrimophol-Binding Protein in Mycobacterium
      tuberculosis.
AB  - Mycobacterial tuberculosis (Mtb) is able to preserve its intrabacterial pH (pHIB)
      near neutrality in the acidic phagosomes of immunologically activated macrophages
      and to cause lethal pathology in immunocompetent mice. In contrast, when its
      ability to maintain pHIB homeostasis is genetically compromised, Mtb dies in
      acidic phagosomes and is attenuated in the mouse. Compounds that phenocopy the
      genetic disruption of Mtb's pHIB homeostasis could serve as starting points for
      drug development in their own right or through identification of their targets. A
      previously reported screen of a natural product library identified a
      phloroglucinol, agrimophol, that lowered Mtb's pHIB and killed Mtb at an acidic
      extrabacterial pH. Inability to identify agrimophol-resistant mutants of Mtb
      suggested that the compound may have more than one target. Given that
      polyphenolic compounds may undergo covalent reactions, we attempted an affinity
      based method for target identification. The structure-activity relationship of
      synthetically tractable polyhydroxy diphenylmethane analogs with equivalent
      bioactivity informed the design of a bioactive agrimophol alkyne. After click
      chemistry reaction with azido-biotin and capture on streptavidin, the
      biotinylated agrimophol analog pulled down the Mtb protein Rv3852, a predicted
      membrane protein that binds DNA in vitro. A ligand-protein interaction between
      agrimophol and recombinant Rv3852 was confirmed by isothermal calorimetry (ITC)
      and led to disruption of Rv3852's DNA binding function. However, genetic deletion
      of rv3852 in Mtb did not phenocopy the effect of agrimophol on Mtb, perhaps
      because of redundancy of its function. 

PMID- 25978363
TI  - Improvement of spatial memory disorder and hippocampal damage by exposure to
      electromagnetic fields in an Alzheimer's disease rat model.
AB  - Although some epidemiological investigations showed a potential association
      between long-term exposure of extremely low frequency electromagnetic fields (ELF
      EMF) and Alzheimer's disease (AD), no reasonable mechanism can explain this
      association, and the related animal experiments are rare. In this study, ELF-EMF
      exposure (50 Hz 400 uT 60 d) combined with D-galactose intraperitoneal (50 mg/kg,
      q.d., 42 d) and Abeta25-35 hippocampal (5 MUl/unilateral, bilateral, single-dose)
      injection was implemented to establish a complex rat model. Then the effects of
      ELF-EMF exposure on AD development was studied by using the Morris water maze,
      pathological analysis, and comparative proteomics. The results showed that ELF
      EMF exposure delayed the weight gain of rats, and partially improved cognitive
      and clinicopathologic symptoms of AD rats. The differential proteomic analysis
      results suggest that synaptic transmission, oxidative stress, protein
      degradation, energy metabolism, Tau aggregation, and inflammation involved in the
      effects mentioned above. Therefore, our findings indicate that certain conditions
      of ELF-EMF exposure could delay the development of AD in rats.

PMID- 25978365
TI  - Correction: Genetic Diversity of the KIR/HLA System and Susceptibility to
      Hepatitis C Virus-Related Diseases.

PMID- 25978364
TI  - Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature
      Swine.
AB  - BACKGROUND: Ossabaw miniature swine when fed a diet high in fructose, saturated
      fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic
      steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was
      conducted to further characterize the development of NASH in this large animal
      model. METHODS: Ossabaw swine were fed standard chow (control group; n = 6) or
      NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver
      histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention.
      Hepatic apoptosis and lipid levels were assessed at week 24. RESULTS: The NASH
      diet group developed metabolic syndrome and progressive histologic features of
      NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to
      extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which
      progressed to moderate fibrosis, and (c) Kupffer cell accumulation with
      vacuolization at 8 weeks which progressed through week 24. The NASH diet group
      showed increased hepatocyte apoptosis that correlated with hepatic total and free
      cholesterol and free fatty acids, but not esterified cholesterol or
      triglycerides. CONCLUSIONS: This report further characterizes the progression of
      diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet:
      (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or
      excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes
      the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it
      is correlated more significantly with hepatic free cholesterol than hepatic free
      fatty acids and had no correlation with hepatic triglycerides.

PMID- 25978366
TI  - Modelling circulating tumour cells for personalised survival prediction in
      metastatic breast cancer.
AB  - Ductal carcinoma is one of the most common cancers among women, and the main
      cause of death is the formation of metastases. The development of metastases is
      caused by cancer cells that migrate from the primary tumour site (the mammary
      duct) through the blood vessels and extravasating they initiate metastasis. Here,
      we propose a multi-compartment model which mimics the dynamics of tumoural cells
      in the mammary duct, in the circulatory system and in the bone. Through a
      branching process model, we describe the relation between the survival times and
      the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44
      and MET). In particular, the model takes into account the gene expression profile
      of circulating tumour cells to predict personalised survival probability. We also
      include the administration of drugs as bisphosphonates, which reduce the
      formation of circulating tumour cells and their survival in the blood vessels, in
      order to analyse the dynamic changes induced by the therapy. We analyse the
      effects of circulating tumour cells on the progression of the disease providing a
      quantitative measure of the cell driver mutations needed for invading the bone
      tissue. Our model allows to design intervention scenarios that alter the patient
      specific survival probability by modifying the populations of circulating tumour
      cells and it could be extended to other cancer metastasis dynamics. 

PMID- 25978367
TI  - Health Effects of Long-Term Rapamycin Treatment: The Impact on Mouse Health of
      Enteric Rapamycin Treatment from Four Months of Age throughout Life.
AB  - Rapamycin, an mTOR inhibitor, has been shown to extend lifespan in a range of
      model organisms. It has been reported to extend lifespan in multiple strains of
      mice, administered chronically or acutely early or late in life. The ability of
      rapamycin to extend health (healthspan) as opposed to life is less well
      documented. To assess the effects chronic rapamycin treatment on healthspan,
      enteric rapamycin was given to male and female C57BL/6J mice starting at 4 months
      of age and continued throughout life. Repeated, longitudinal assessments of
      health in individual animals were made starting at 16 months of age (=12 months
      of treatment) until death. A number of health parameters were improved (female
      grip strength, female body mass and reduced sleep fragmentation in both sexes),
      others showed no significant difference, while at least one (male rotarod
      performance) was negatively affected. Rapamycin treatment affected many measures
      of health in a highly sex-specific manner. While sex-specific phenotypic effects
      of rapamycin treatment have been widely reported, in this study we document sex
      differences in the direction of phenotypic change. Rapamycin-fed males and
      females were both significantly different from controls; however the differences
      were in the opposite direction in measures of body mass, percent fat and resting
      metabolic rate, a pattern not previously reported.

PMID- 25978368
TI  - Short-term outcomes of hip fractures in patients aged 90 years old and over
      receiving surgical intervention.
AB  - BACKGROUND: The knowledge about short-term outcomes of nonagenarians undergoing
      surgery for hip fracture in Asian is limited. METHODS: The patients with hip
      fractures who underwent hip hemiarthroplasty and open reduction with internal
      fixation (ORIF) for management during the period from 2008 to 2012 were
      identified and their medical record was retrospectively reviewed. RESULTS: During
      the study period, a total of 101 patients underwent surgery for management of hip
      fractures, and the age of patients ranged from 90 to 96 years. The sites of hip
      fracture were intertrochanteric (n = 57, 56.4%) and the neck of the femur (n =
      44, 43.6%). Most of the patients had American Society of Anesthesiologists scores
      of 3(n = 55) or 4 (in 44 patients). 80.2% (n = 81) underwent the operation within
      one day after admission; however, there were 13 patients (12.9%) that underwent
      surgery 48 or more hours later. ORIF and hemiarthroplasty were performed for 63
      (62.4%) and 38 (37.6%) patients, respectively. Overall, the 30-day and 1-year
      mortality rates were 9.9% (10/101) and 17.3% (13/75), respectively. Multivariate
      analysis showed that the 30-day mortality was significantly associated only with
      end-stage renal disease (ESRD) (Odds ratio, 11.13, 95% confidence interval, 1.275
      97.881, P = .029). CONCLUSIONS: The short-term outcome of surgical management for
      Asian nonagenarians with hip fractures is favorable in selected patients.

PMID- 25978369
TI  - Medfly Ceratitis capitata as Potential Vector for Fire Blight Pathogen Erwinia
      amylovora: Survival and Transmission.
AB  - Monitoring the ability of bacterial plant pathogens to survive in insects is
      required for elucidating unknown aspects of their epidemiology and for designing
      appropriate control strategies. Erwinia amylovora is a plant pathogenic bacterium
      that causes fire blight, a devastating disease in apple and pear commercial
      orchards. Studies on fire blight spread by insects have mainly focused on
      pollinating agents, such as honeybees. However, the Mediterranean fruit fly
      (medfly) Ceratitis capitata (Diptera: Tephritidae), one of the most damaging
      fruit pests worldwide, is also common in pome fruit orchards. The main objective
      of the study was to investigate whether E. amylovora can survive and be
      transmitted by the medfly. Our experimental results show: i) E. amylovora can
      survive for at least 8 days inside the digestive tract of the medfly and until 28
      days on its external surface, and ii) medflies are able to transmit the bacteria
      from inoculated apples to both detached shoots and pear plants, being the
      pathogen recovered from lesions in both cases. This is the first report on E.
      amylovora internalization and survival in/on C. capitata, as well as the
      experimental transmission of the fire blight pathogen by this insect. Our results
      suggest that medfly can act as a potential vector for E. amylovora, and expand
      our knowledge on the possible role of these and other insects in its life cycle. 

PMID- 25978370
TI  - Effective Swimmer's Action during the Grab Start Technique.
AB  - The external forces applied in swimming starts have been often studied, but using
      direct analysis and simple interpretation data processes. This study aimed to
      develop a tool for vertical and horizontal force assessment based on the
      swimmers' propulsive and structural forces (passive forces due to dead weight)
      applied during the block phase. Four methodological pathways were followed: the
      experimented fall of a rigid body, the swimmers' inertia effect, the development
      of a mathematical model to describe the outcome of the rigid body fall and its
      generalization to include the effects of the inertia, and the experimental
      swimmers' starting protocol analysed with the inclusion of the developed
      mathematical tool. The first three methodological steps resulted in the
      description and computation of the passive force components. At the fourth step,
      six well-trained swimmers performed three 15 m maximal grab start trials and
      three-dimensional (3D) kinetic data were obtained using a six degrees of freedom
      force plate. The passive force contribution to the start performance obtained
      from the model was subtracted from the experimental force due to the swimmers
      resulting in the swimmers' active forces. As expected, the swimmers' vertical and
      horizontal active forces accounted for the maximum variability contribution of
      the experimental forces. It was found that the active force profile for the
      vertical and horizontal components resembled one another. These findings should
      be considered in clarifying the active swimmers' force variability and the
      respective geometrical profile as indicators to redefine steering strategies. 

PMID- 25978371
TI  - Antitumor Effects of Oncolytic Adenovirus-Carrying siRNA Targeting Potential
      Oncogene EphA3.
AB  - Conditionally replicating adenoviruses (CRAds) armed with antitumor transgenes
      hold promise for cancer treatment. In previous studies, we showed that the 1504
      siRNA targeting potential oncogene EphA3 was an efficient therapeutic transgene
      and that the telomerase reverse transcriptase promoter (TERTp) driving the CRAd
      was a more advanced generation of CRAd. Therefore, we combined Ad-TERTp-E1A-1504
      by inserting 1504-siRNA into the CRAd to study its antitumor effects and
      mechanism of action, using Ad-TERTp-E1A-NC and nonreplicating adenovirus carrying
      1504-siRNA as controls. Cell viability assays and ED50 studies of growth
      inhibition confirmed that Ad-TERTp-E1A-1504 has 3.5- and 1,400-fold greater
      ability to kill EphA3- and TERT-expressing tumor cells compared to Ad-TERTp-E1A
      NC and Ad-DeltaE1A-1504, respectively. Also, Ad-TERTp-E1A-1504 had little effect
      on cells that modestly expressed EphA3 and TERT such as 2BS. The antitumor
      efficacy of Ad-TERTp-E1A-1504 was also validated in vivo. Furthermore, the virus
      yield of Ad-TERTp-E1A-1504 in C4-2B was ~1,000 times greater than that in 2BS. No
      obvious differences were observed between Ad-TERTp-E1A-1504 and Ad-TERTp-E1A-NC.
      Both acridine orange staining and Beclin1 protein measurements indicated that
      autophagy with Ad-TERTp-E1A-1504 at 5 and 10 MOI was higher than that of Ad-TERTp
      E1A-NC. Finally, the classical negatively regulated autophagy signaling pathway,
      PI3K/AKT/mTOR, was suppressed (reduced phosphorylated form) in contrast to NC,
      and that this was mediated by 1504-siRNA. Thus, Ad- TERTp-E1A-1504 does not harm
      normal cells but has dual inhibiting and killing effects on TERT- and EphA3
      positive tumor cells, and this effect is mediated by the AKT/mTOR signaling
      pathway via induction of autophagy. These data may offer a foundation for novel
      antitumor therapies targeting this mechanism. 

PMID- 25978373
TI  - Robust biometrics based authentication and key agreement scheme for multi-server
      environments using smart cards.
AB  - Biometrics authenticated schemes using smart cards have attracted much attention
      in multi-server environments. Several schemes of this type where proposed in the
      past. However, many of them were found to have some design flaws. This paper
      concentrates on the security weaknesses of the three-factor authentication scheme
      by Mishra et al. After careful analysis, we find their scheme does not really
      resist replay attack while failing to provide an efficient password change phase.
      We further propose an improvement of Mishra et al.'s scheme with the purpose of
      preventing the security threats of their scheme. We demonstrate the proposed
      scheme is given to strong authentication against several attacks including
      attacks shown in the original scheme. In addition, we compare the performance and
      functionality with other multi-server authenticated key schemes. 

PMID- 25978372
TI  - Left Ventricular Global Longitudinal Strain (GLS) Is a Superior Predictor of All
      Cause and Cardiovascular Mortality When Compared to Ejection Fraction in Advanced
      Chronic Kidney Disease.
AB  - BACKGROUND: Echocardiographic global longitudinal strain (GLS) is increasingly
      recognised as a more effective technique than conventional ejection fraction (EF)
      in detecting subtle changes in left ventricular (LV) function. This study
      investigated the prognostic value of GLS over EF in patients with advanced
      Chronic Kidney Disease (CKD). METHODS: The study included 183 patients (57% male,
      63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients
      died in a follow up of 7.8 +/- 4.4 years and 41% of deaths were due to
      cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle
      tracking and EF was measured using Simpson's biplane method. Cox proportional
      hazard models were used to assess the association of measures of LV function and
      all- cause and CV mortality. RESULTS: The mean GLS at baseline was -13.6 +/- 4.3%
      and EF was 45 +/- 11%. GLS was a significant predictor of all-cause [Hazard Ratio
      (HR) 1.09 95%; Confidence Interval (CI) 1.02-1.16; p = 0.01] and CV mortality (HR
      1.16 95%; CI 1.04-1.30; p = 0.008) following adjustment for relevant clinical
      variables including LV mass index (LVMI) and EF. GLS also had greater predictive
      power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%)
      was associated with a 5.6-fold increased unadjusted risk of CV mortality in
      patients with preserved EF. CONCLUSIONS: In this cohort of patients with advanced
      CKD, GLS is a more sensitive predictor of overall and CV mortality compared to
      EF. Studies of larger populations in CKD are required to confirm that GLS
      provides additive prognostic value in patients with preserved EF.

PMID- 25978374
TI  - Lactobacillus fermentum ZYL0401 Attenuates Lipopolysaccharide-Induced Hepatic TNF
      alpha Expression and Liver Injury via an IL-10- and PGE2-EP4-Dependent Mechanism.
AB  - Lipopolysaccharide (LPS) has essential role in the pathogenesis of D
      galactosamine-sensitized animal models and alcoholic liver diseases of humans, by
      stimulating release of pro-inflammatory mediators that cause hepatic damage and
      intestinal barrier impairment. Oral pretreatment of probiotics has been shown to
      attenuate LPS-induced hepatic injury, but it is unclear whether the effect is
      direct or due to improvement in the intestinal barrier. The present study tested
      the hypothesis that pretreatment with probiotics enables the liver to withstand
      directly LPS-induced hepatic injury and inflammation. In a mouse model of LPS
      induced hepatic injury, the levels of hepatic tumor necrosis factor-alpha (TNF
      alpha) and serum alanine aminotransferase (ALT) of mice with depleted intestinal
      commensal bacteria were not significantly different from that of the control
      models. Pre-feeding mice for 10 days with Lactobacillus fermentum ZYL0401 (LF41),
      significantly alleviated LPS-induced hepatic TNF-alpha expression and liver
      damage. After LF41 pretreatment, mice had dramatically more L.fermentum-specific
      DNA in the ileum, significantly higher levels of ileal cyclooxygenase (COX)-2 and
      interleukin 10 (IL-10) and hepatic prostaglandin E2 (PGE2). However, hepatic COX
      1, COX-2, and IL-10 protein levels were not changed after the pretreatment. There
      were also higher hepatic IL-10 protein levels after LPS challenge in LF41
      pretreated mice than in the control mice. Attenuation of hepatic TNF-alpha was
      mediated via the PGE2/E prostanoid 4 (EP4) pathway, and serum ALT levels were
      attenuated in an IL-10-dependent manner. A COX-2 blockade abolished the increase
      in hepatic PGE2 and IL-10 associated with LF41. In LF41-pretreated mice, a
      blockade of IL-10 caused COX-2-dependent promotion of hepatic PGE2, without
      affecting hepatic COX-2 levels. In LF41-pretreated mice, COX2 prevented enhancing
      TNF-alpha expression in both hepatic mononuclear cells and the ileum, and averted
      TNF-alpha-mediated increase in intestinal permeability. Together, we demonstrated
      that LF41 pre-feeding enabled the liver to alleviate LPS-induced hepatic TNF
      alpha expression and injury via a PGE2-EP4- and IL-10-dependent mechanism.

PMID- 25978375
TI  - Recognition of DNA Termini by the C-Terminal Region of the Ku80 and the DNA
      Dependent Protein Kinase Catalytic Subunit.
AB  - DNA double strand breaks (DSBs) can be generated by endogenous cellular processes
      or exogenous agents in mammalian cells. These breaks are highly variable with
      respect to DNA sequence and structure and all are recognized in some context by
      the DNA-dependent protein kinase (DNA-PK). DNA-PK is a critical component
      necessary for the recognition and repair of DSBs via non-homologous end joining
      (NHEJ). Previously studies have shown that DNA-PK responds differentially to
      variations in DSB structure, but how DNA-PK senses differences in DNA substrate
      sequence and structure is unknown. Here we explore the enzymatic mechanisms by
      which DNA-PK is activated by various DNA substrates and provide evidence that the
      DNA-PK is differentially activated by DNA structural variations as a function of
      the C-terminal region of Ku80. Discrimination based on terminal DNA sequence
      variations, on the other hand, is independent of the Ku80 C-terminal interactions
      and likely results exclusively from DNA-dependent protein kinase catalytic
      subunit interactions with the DNA. We also show that sequence differences in DNA
      termini can drastically influence DNA repair through altered DNA-PK activation.
      These results indicate that even subtle differences in DNA substrates influence
      DNA-PK activation and ultimately the efficiency of DSB repair. 

PMID- 25978376
TI  - Prevalence and risk factors of chronic otitis media: the Korean National Health
      and Nutrition Examination Survey 2010-2012.
AB  - BACKGROUND: The performance of nationwide studies of chronic otitis media (COM)
      in adults has been insufficient in Korea. We evaluated the prevalence and risk
      factors of COM in Korea. METHODS: This study was conducted using data from the
      fifth Korean National Health and Nutrition Examination Survey (n = 23,621). After
      excluding the subjects under 20 year old and suffered from cancers, 16,063
      patients were evaluated for COM. Participants underwent a medical interview,
      physical examination, endoscopic examination, and blood and urine test. COM was
      diagnosed by trained residents in the Department of Otorhinolaryngology using an
      ear, nose, and throat questionnaire and otoendoscopy findings. Data on the
      presence and absence of COM were collected. Multivariate logistic regression
      analyses were performed to identify its risk factors. RESULTS: Of the 16,063
      participants aged above 20 year old, the weighted prevalence of COM was 3.8%. In
      the multivariate analyses, the following factors showed high odds ratios (ORs)
      for COM: pulmonary tuberculosis (adjusted OR, 1.78; 95% confidence interval [CI],
      1.06-3.01), chronic rhinosinusitis (adjusted OR, 1.87; 95% CI, 1.17-2.98), mild
      hearing impairment (adjusted OR, 1.95; 95% CI, 1.34-2.85), moderate hearing
      impairment (adjusted OR, 4.00; 95% CI, 2.21-7.22), tinnitus (adjusted OR, 1.82;
      95% CI, 1.34-2.49), increased hearing thresholds in pure tone audiometry in the
      right ear (adjusted OR, 1.02; 95% CI, 1.01-1.03), and left ear (adjusted OR,
      1.03; 95% CI, 1.02-1.04). The following factors showed low odds ratios for COM:
      hepatitis B (adjusted OR, 0.28; 95% CI, 0.08-0.94) and rhinitis (adjusted OR,
      0.60; 95% CI, 0.42-0.88). In addition, high levels of vitamin D, lead, and
      cadmium, EQ-5D index; and low red blood cell counts were associated with
      development of COM (Student's t-test, P < 0.01). CONCLUSIONS: Our population
      based study showed that COM is not rare in Korea, and its development may be
      associated with various host and environmental factors. Further research on its
      relationships and the pathogenesis are needed.

PMID- 25978377
TI  - Dynamic Expression of Novel MiRNA Candidates and MiRNA-34 Family Members in Early
      to Mid-Gestational Fetal Keratinocytes Contributes to Scarless Wound Healing by
      Targeting the TGF-beta Pathway.
AB  - BACKGROUND: Early- to mid-gestational fetal mammalian skin wounds heal rapidly
      and without scarring. Keratinocytes (KCs) have been found to exert important
      effects on the regulation of fibroblasts. There may be significant differences of
      gestational fetal KCs at different ages. The advantages in early- to mid
      gestational fetal KCs could lead to fetal scarless wound healing. METHODS: KCs
      from six human fetal skin samples were divided into two groups: a mid-gestation
      group (less than 28 weeks of gestational age) and a late-gestation group (more
      than 28 weeks of gestational age). RNA extracted from KCs was used to prepare a
      library of small RNAs for next-generation sequencing (NGS). To uncover potential
      novel microRNA (miRNAs), the mirTools 2.0 web server was used to identify
      candidate novel human miRNAs from the NGS data. Other bioinformatical analyses
      were used to further validate the novel miRNAs. The expression levels of the
      miRNAs were further confirmed by real-time quantitative RT-PCR. RESULTS: A total
      of 61.59 million reads were mapped to 1,170 known human miRNAs in miRBase. Among
      a total of 202 potential novel miRNAs uncovered, 106 candidates have a higher
      probability of being novel human miRNAs. A total of 110 miRNAs, including 22
      novel miRNA candidates, were significantly differently expressed between mid- and
      late-gestational fetal KCs. Thirty-three differentially expressed miRNAs and miR
      34 family members are correlated with the transforming growth factor-beta (TGF
      beta) pathway. CONCLUSIONS: Taken together, our results provide compelling
      evidence supporting the existence of 106 novel miRNAs and the dynamic expression
      of miRNAs that extensively targets the TGF-beta pathway at different gestational
      ages in fetal KCs. MiRNAs showing altered expression at different gestational
      ages in fetal KCs may contribute to scarless wound healing in early- to mid
      gestational fetal KCs, and thus may be new targets for potential scar prevention
      and reduction therapies.

PMID- 25978378
TI  - Changes in urination according to the sound of running water using a mobile phone
      application.
AB  - OBJECTIVE: The sound of running water (SRW) has been effectively used for toilet
      training during toddlerhood. However, the effect of SRW on voiding functions in
      adult males with lower urinary tract symptoms (LUTS) has not been evaluated. To
      determine the effect of SRW on urination in male patients with LUTS, multiple
      voiding parameters of uroflowmetry with postvoid residual urine (PVR) were
      assessed according to the presence of SRW played by a mobile application.
      METHODS: Eighteen consecutive male patients with LUTS were prospectively enrolled
      between March and April 2014. Uroflowmetry with PVR measured by a bladder scan
      was randomly performed once weekly for two consecutive weeks with and without SRW
      in a completely sealed room after pre-checked bladder volume was scanned to be
      more than 150 cc. SRW was played with river water sounds amongst relaxed melodies
      from a smartphone mobile application. RESULTS: The mean age of enrolled patients
      and their mean International Prostate Symptom Score (IPSS) were 58.9 +/- 7.7
      years (range: 46-70) and 13.1 +/- 5.9, respectively. All patients had not been
      prescribed any medications, including alpha-blockers or anti-muscarinic agents,
      in the last 3 months. There was a significant increase in mean peak flow rate
      (PFR) with SRW in comparison to without SRW (15.7 mL/s vs. 12.3 mL/s,
      respectively, p = 0.0125). However, there were no differences in other
      uroflowmetric parameters, including PVR. CONCLUSIONS: The study showed that SRW
      from a mobile phone application may be helpful in facilitating voiding functions
      by increasing PFR in male LUTS patients.

PMID- 25978379
TI  - Structural and Kinetic Characterization of Thymidine Kinase from Leishmania
      major.
AB  - Leishmania spp. is a protozoan parasite and the causative agent of leishmaniasis.
      Thymidine kinase (TK) catalyses the transfer of the gamma-phosphate of ATP to 2'
      deoxythymidine (dThd) forming thymidine monophosphate (dTMP). L. major Type II TK
      (LmTK) has been previously shown to be important for infectivity of the parasite
      and therefore has potential as a drug target for anti-leishmanial therapy. In
      this study, we determined the enzymatic properties and the 3D structures of holo
      forms of the enzyme. LmTK efficiently phosphorylates dThd and dUrd and has high
      structural homology to TKs from other species. However, it significantly differs
      in its kinetic properties from Trypanosoma brucei TK since purines are not
      substrates of the enzyme and dNTPs such as dUTP inhibit LmTK. The enzyme had Km
      and kcat values for dThd of 1.1 MUM and 2.62 s(-1) and exhibits cooperative
      binding for ATP. Additionally, we show that the anti-retroviral prodrug
      zidovudine (3-azido-3-deoxythymidine, AZT) and 5'-modified dUrd can be readily
      phosphorylated by LmTK. The production of recombinant enzyme at a level suitable
      for structural studies was achieved by the construction of C-terminal truncated
      versions of the enzyme and the use of a baculoviral expression system. The
      structures of the catalytic core of LmTK in complex with dThd, the negative
      feedback regulator dTTP and the bi-substrate analogue AP5dT, were determined to
      2.74, 3.00 and 2.40 A, respectively, and provide the structural basis for
      exclusion of purines and dNTP inhibition. The results will aid the process of
      rational drug design with LmTK as a potential target for anti-leishmanial drugs.

PMID- 25978380
TI  - Adducin is involved in endothelial barrier stabilization.
AB  - Adducins tightly regulate actin dynamics which is critical for endothelial
      barrier function. Adducins were reported to regulate epithelial junctional
      remodeling by controlling the assembly of actin filaments at areas of cell-cell
      contact. Here, we investigated the role of alpha-adducin for endothelial barrier
      regulation by using microvascular human dermal and myocardial murine endothelial
      cells. Parallel transendothelial electrical resistance (TER) measurements and
      immunofluorescence analysis revealed that siRNA-mediated adducin depletion
      impaired endothelial barrier formation and led to severe fragmentation of VE
      cadherin immunostaining at cell-cell borders. To further test whether the
      peripheral localization of alpha-adducin is functionally linked with the
      integrity of endothelial adherens junctions, junctional remodeling was induced by
      a Ca(2+)-switch assay. Ca(2+)-depletion disturbed both linear vascular
      endothelial (VE)-cadherin and adducin location along cell junctions, whereas
      their localization was restored following Ca(2+)-repletion. Similar results were
      obtained for alpha-adducin phosphorylated at a site typical for PKA (pSer481). To
      verify that endothelial barrier properties and junction reorganization can be
      effectively modulated by altering Ca(2+)-concentration, TER measurements were
      performed. Thus, Ca(2+)-depletion drastically reduced TER, whereas Ca(2+)
      repletion led to recovery of endothelial barrier properties resulting in
      increased TER. Interestingly, the Ca(2+)-dependent increase in TER was also
      significantly reduced after efficient alpha-adducin downregulation. Finally, we
      report that inflammatory mediator-induced endothelial barrier breakdown is
      associated with loss of alpha-adducin from the cell membrane. Taken together, our
      results indicate that alpha-adducin is involved in remodeling of endothelial
      adhesion junctions and thereby contributes to endothelial barrier regulation.

PMID- 25978382
TI  - Biological Significance of Photoreceptor Photocycle Length: VIVID Photocycle
      Governs the Dynamic VIVID-White Collar Complex Pool Mediating Photo-adaptation
      and Response to Changes in Light Intensity.
AB  - Most organisms on earth sense light through the use of chromophore-bearing
      photoreceptive proteins with distinct and characteristic photocycle lengths, yet
      the biological significance of this adduct decay length is neither understood nor
      has been tested. In the filamentous fungus Neurospora crassa VIVID (VVD) is a
      critical player in the process of photoadaptation, the attenuation of light
      induced responses and the ability to maintain photosensitivity in response to
      changing light intensities. Detailed in vitro analysis of the photochemistry of
      the blue light sensing, FAD binding, LOV domain of VVD has revealed residues
      around the site of photo-adduct formation that influence the stability of the
      adduct state (light state), that is, altering the photocycle length. We have
      examined the biological significance of VVD photocycle length to photoadaptation
      and report that a double substitution mutant (vvdI74VI85V), previously shown to
      have a very fast light to dark state reversion in vitro, shows significantly
      reduced interaction with the White Collar Complex (WCC) resulting in a
      substantial photoadaptation defect. This reduced interaction impacts
      photoreceptor transcription factor WHITE COLLAR-1 (WC-1) protein stability when
      N. crassa is exposed to light: The fast-reverting mutant VVD is unable to form a
      dynamic VVD-WCC pool of the size required for photoadaptation as assayed both by
      attenuation of gene expression and the ability to respond to increasing light
      intensity. Additionally, transcription of the clock gene frequency (frq) is
      sensitive to changing light intensity in a wild-type strain but not in the fast
      photo-reversion mutant indicating that the establishment of this dynamic VVD-WCC
      pool is essential in general photobiology and circadian biology. Thus, VVD
      photocycle length appears sculpted to establish a VVD-WCC reservoir of sufficient
      size to sustain photoadaptation while maintaining sensitivity to changing light
      intensity. The great diversity in photocycle kinetics among photoreceptors may be
      viewed as reflecting adaptive responses to specific and salient tasks required by
      organisms to respond to different photic environments. 

PMID- 25978381
TI  - Macrophage polarization reflects T cell composition of tumor microenvironment in
      pediatric classical Hodgkin lymphoma and has impact on survival.
AB  - Macrophages have been implicated in the pathogenesis of classical Hodgkin
      lymphoma (cHL) and have been suggested to have a negative impact on outcome. Most
      studies addressing the role of macrophages in cHL have relied on identification
      of macrophages by generic macrophage antigens, e.g., CD68. We have therefore
      conducted an in situ analysis of macrophage polarization in a series of 100
      pediatric cHL (pcHL) cases using double staining immunohistochemistry, combining
      CD68 or CD163 with pSTAT1 (M1-like) or CMAF (M2-like). M1- or M2-polarised
      microenvironment was defined by an excess of one population over the other
      (>1.5). Expression of STAT1 and LYZ genes was also evaluated by RT-qPCR. Patients
      <14 years and EBV+ cases displayed higher numbers of CD68+pSTAT1+ cells than
      older children and EBV- cases, respectively (P=0.01 and P=0.02). A cytotoxic
      tumor microenvironment, defined by a CD8+/FOXP3+ ratio >1.5 was associated with
      higher numbers of CD68+pSTAT1+ (P=0.025) and CD163+pSTAT1+ macrophages
      (P<0.0005). Levels of STAT1 and LYZ expression were associated with the numbers
      of CD68+pSTAT1+ macrophages. EBV+ cHL cases disclosed a predominant M1 polarized
      microenvironment similar to Th1 mediated inflammatory disorders, while EBV- cHL
      showed a predominant M2 polarized microenvironment closer to Th2 mediated
      inflammatory diseases. Better overall-survival (OS) was observed in cases with
      higher numbers of CD163+pSTAT1+ macrophages (P=0.02) while larger numbers of
      CD163+CMAF+ macrophages were associated with worse progression-free survival
      (PFS) (P=0.02). Predominant M1-like polarization as disclosed by
      CD163+pSTAT1+/CD163+CMAF+ ratio > 1.5 was associated with better OS (P= 0.037).
      In conclusion, macrophage polarization in pcHL correlates with prevalent local T
      cell response and may be influenced by the EBV-status of neoplastic cells.
      Besides, M1-like and M2-like macrophages displayed differential effects on
      outcome in pcHL. 

PMID- 25978384
TI  - [The Russian part of the human proteome project:first results and prospects].
AB  - The article summarizes the achievements of the pilot phase (2010-2014) of the
      Russian part of the international project "Human Proteome" and identifies the
      directions for further work on the study of the human chromosome 18 proteome in
      the framework of the project main phase (2015-2022). The pilot phase of the
      project was focused on the detection of at least one protein for each chromosome
      18 protein-coding gene in three types of the biological material. The application
      of mass spectrometric detection of proteins by the methods of multiple reactions
      monitoring (MRM) and gene-centric approach made it possible to detect 95% of
      master forms of proteins, for 60% of which the quantitative assessment of the
      protein content was obtained in at least one type of the biological material. The
      task of the main phase of the project is to measure the proteome size of healthy
      individuals, taking into account the modified protein forms, providing for both
      the bioinformatics prediction of the quantity of proteins types and the selective
      experimental measurement of single proteoforms. Since the ranges of protein
      concentrations corresponding to the normal physiological state have not been
      identified, the work of the main phase of the project is focused on the study of
      clinically healthy individuals. The absence of these data complicates
      significantly the interpretation of the patients' blood proteomic profiles and
      prevents creating diagnostic tests. In the long term prospect, implementation of
      the project envisages development of a diagnostic test system based on multiple
      reactions monitoring (MRM) for quantitative measurement of the protein forms
      associated with some diseases. Development of such test systems will allow
      predicting the extent of risk of different diseases, diagnosing a disease at its
      early stage and monitoring the effectiveness of the treatment. 

PMID- 25978385
TI  - [Molecular organization of the microsomal oxidative system: a new connotation for
      an old term].
AB  - The central role that cytochromes P450 play in the metabolism of drugs and other
      xenobiotics makes these enzymes a major subject for studies of drug disposition,
      adverse drug effects and drug-drug interactions. Although there has been
      tremendous success in delineating P450 mechanisms, the concept of the drug
      metabolizing ensemble as a functionally integrated system remains undeveloped.
      However, eukaryotic cells typically possess a multitude of different P450 enzymes
      that are co-localized in the membrane of endoplasmic reticulum (ER) and interact
      with each other with the formation of dynamic heteromeric complexes (mixed
      oligomers). Appreciation of the importance of developing an integral, systems
      approach to the ensemble of cytochromes P450 as an integral system inspired
      growing interest of researchers to the molecular organization of microsomal
      monooxygenase, which remained in the focus of research of academician Archakov
      for over 40 years. Fundamental studies carried out under his guidance have an
      important impact on our current concepts in this area. Further exploration of the
      molecular organization of the system of microsomal monooxygenase as an integral
      multienzyme and multifunctional system will have an essential impact on our
      understanding of the key factors that determine the changes in human drug
      metabolism and other P450-related functions in development, aging, and disease,
      as well as under influence of drugs, food ingredients, and environmental
      contaminants. 

PMID- 25978386
TI  - [Electrochemical methods for biomedical investigations].
AB  - In the review, authors discussed recently published experimental data concerning
      highly sensitive electrochemical methods and technologies for biomedical
      investigations in the postgenomic era. Developments in electrochemical biosensors
      systems for the analysis of various bio objects are also considered: cytochrome
      P450s, cardiac markers, bacterial cells, the analysis of proteins based on
      electro oxidized amino acids as a tool for analysis of conformational events. The
      electroanalysis of catalytic activity of cytochromes P450 allowed developing
      system for screening of potential substrates, inhibitors or modulators of
      catalytic functions of this class of hemoproteins. The highly sensitive quartz
      crystal microbalance (QCM) immunosensor has been developed for analysis of bio
      affinity interactions of antibodies with troponin I in plasma. The QCM technique
      allowed real-time monitoring of the kinetic differences in specific interactions
      and nonspecific sorption, with out multiple labeling procedures and separation
      steps. The affinity binding process was characterized by the association (ka) and
      the dissociation (kd) kinetic constants and the equilibrium association (K)
      constant, calculated using experimental data. Based on the electroactivity of
      bacterial cells, the electrochemical system for determination of sensitivity of
      the microbial cells to antibiotics cefepime, ampicillin, amikacin, and
      erythromycin was proposed. It was shown that the minimally detectable cell number
      corresponds to 106 CFU per electrode. The electrochemical method allows
      estimating the degree of E.coli JM109 cells resistance to antibiotics within 2-5
      h. Electrosynthesis of polymeric analogs of antibodies for myoglobin (molecularly
      imprinted polymer, MIP) on the surface of graphite screen-printed electrodes as
      sensor elements with o- phenylenediamine as the functional monomer was developed.
      Molecularly imprinted polymers demonstrate selective complementary binding of a
      template protein molecule (myoglobin) by the "key-lock" principle.

PMID- 25978383
TI  - The Recent Evolution of a Maternally-Inherited Endosymbiont of Ticks Led to the
      Emergence of the Q Fever Pathogen, Coxiella burnetii.
AB  - Q fever is a highly infectious disease with a worldwide distribution. Its
      causative agent, the intracellular bacterium Coxiella burnetii, infects a variety
      of vertebrate species, including humans. Its evolutionary origin remains almost
      entirely unknown and uncertainty persists regarding the identity and lifestyle of
      its ancestors. A few tick species were recently found to harbor maternally
      inherited Coxiella-like organisms engaged in symbiotic interactions, but their
      relationships to the Q fever pathogen remain unclear. Here, we extensively
      sampled ticks, identifying new and atypical Coxiella strains from 40 of 58
      examined species, and used this data to infer the evolutionary processes leading
      to the emergence of C. burnetii. Phylogenetic analyses of multi-locus typing and
      whole-genome sequencing data revealed that Coxiella-like organisms represent an
      ancient and monophyletic group allied to ticks. Remarkably, all known C. burnetii
      strains originate within this group and are the descendants of a Coxiella-like
      progenitor hosted by ticks. Using both colony-reared and field-collected gravid
      females, we further establish the presence of highly efficient maternal
      transmission of these Coxiella-like organisms in four examined tick species, a
      pattern coherent with an endosymbiotic lifestyle. Our laboratory culture assays
      also showed that these Coxiella-like organisms were not amenable to culture in
      the vertebrate cell environment, suggesting different metabolic requirements
      compared to C. burnetii. Altogether, this corpus of data demonstrates that C.
      burnetii recently evolved from an inherited symbiont of ticks which succeeded in
      infecting vertebrate cells, likely by the acquisition of novel virulence factors.

PMID- 25978387
TI  - [Physico-chemical methods for studing beta-amyloid aggregation].
AB  - Alzheimer's disease is the most prevalent neurodegenerative pathology. According
      to the amyloid cascade hypothesis, a key event of the Alzheimer's disease
      pathogenesis is a transition of the beta-amyloid peptide (Abeta) from the
      monomeric form to the aggregated state. The mechanism of Abeta aggregation is
      intensively studied in vitro, by means of synthetic peptides and various physico
      chemical methods allowing evaluation of size, molecular structure, and morphology
      of the formed aggregates. The paper reviews both the well-known and recently
      introduced physico-chemical methods for analysis of Abeta aggregation, including
      microscopu, optical and fluorescent methods, method of electron paramagnetic
      resonance, electrochemical and electrophoretic methods, gel-filtration, and mass
      spectrometric methods. Merits and drawbacks of the methods are discussed. The
      unique possibility to simultaneously observe Abeta monomers as well oligomers and
      large aggregates by means of atomic force microscopy or fluorescence correlation
      spectroscopy is emphasized. The high detection sensitivity of the latter method,
      monitoring the aggregation process in Abeta solutions at low peptide
      concentrations is underlined. Among mass spectrometric methods, the ion mobility
      mass spectrometry is marked out as a method enabling to obtain information about
      both the spectrum of Abeta oligomers and their structure. It is pointed out that
      the use of several methods giving the complementary data about Abeta aggregates
      is the best experimental approach to studying the process of b-amyloid peptide
      aggregation in vitro.

PMID- 25978388
TI  - [Pharmacological agents and transport nanosystems based on plant phospholipids].
AB  - A new generation of plant phosphatidylcholine (PC)-based pharmacological agents
      has been developed under academician A.I. Archakov leadership at the Institute of
      Biomedical Chemistry (IBMC). For their production a unique technology allowing to
      obtain dry lyophilized phospholipid nanoparticles of 30 nm was elaborated. The
      successful practical application of PC nanoparticles as a drug agent may be
      illustrated by Phosphogliv (oral and injection formulations). Being developed at
      IBMC for the treatment of liver diseases, including viral hepatitis, Phosphogliv
      (currently marketed by the "Pharmstandard" company) is approved for clinical
      application in 2000, and is widely used in medical practice. Based on the
      developed and scaled in IBMC technology of prerparation of ultra small size
      phospholipid nanoparticles without the use of detergents/surfactants and
      stabilizers another drug preparation, Phospholipovit, exhibiting pronounced
      hypolipidemic properties has been obtained. Recently completed preclinical
      studies have shown that PC nanoparticles of 20-30 nm activate reverse cholesterol
      transport (RCT) and in this context it is more active than well known foreign
      preparation Essentiale. Phospholipovit is now at the stage of clinical trials
      (phase 1 completed). PC was also used as a basis for the development of a
      transport nanosystem with a particles size of 20-25 nm in diameter and
      incorporation of various drug substances from various therapeutic groups. Using
      several drugs substances as an example, increased bioavailability and specific
      activity were demonstrated for the formulations equipped with such transport
      nanosystem. Formulations equipped with the transport nanosystems have been
      developed for such pharmacological agents as doxorubicin, rifampin, budesonide,
      chlorin E6, prednisone, and others.

PMID- 25978389
TI  - [Optical surface plasmon resonance biosensors in molecular fishing].
AB  - An optical biosensor employing surface plasmon resonance is a highly efficient
      instrument applicable for direct real time registration of molecular interactions
      without additional use of any labels or coupled processes. As an independent
      approach it is especially effective in analysis of various ligand receptor
      interactions. SPR-biosensors are used for validation of studies on intermolecular
      interactions in complex biological systems (affinity profiling of various groups
      of proteins, etc.). Recently, potential application of the SPR-biosensor for
      molecular fishing (direct affinity binding of target molecules from complex
      biological mixtures on the optical biosensor surface followed by their elution
      for identification by LC-MS/MS) has been demonstrated. Using SPR-biosensors in
      such studies it is possible to solve the following tasks: (a) SPR-based selection
      of immobilization conditions required for the most effective affinity separation
      of a particular biological sample; (b) SPR-based molecular fishing for subsequent
      protein identification by mass spectrometry; (c) SPR-based validation of the
      interaction of identified proteins with immobilized ligand. This review considers
      practical application of the SPR technology in the context of recent studies
      performed in the Institute of Biomedical Chemistry on molecular fishing of real
      biological objects.

PMID- 25978390
TI  - [AFM-based technologies as the way towards the reverse Avogadro number].
AB  - Achievement of the concentration detection limit for proteins at the level of the
      reverse Avogadro number determines the modern development of proteomics. In this
      review, the possibility of approximating the reverse Avogadro number by using
      nanotechnological methods (AFM-based fishing with mechanical and electrical
      stimulation, nanowire detectors, and other methods) are discussed. The ability of
      AFM to detect, count, visualize and characterize physico-chemical properties of
      proteins at concentrations up to 10(-17)-10(-18) M is demonstrated. The
      combination of AFM-fishing with mass-spectrometry allows the identification of
      proteins not only in pure solutions, but also in multi-component biological
      fluids (serum). The possibilities to improve the biospecific fishing efficiency
      by use of SOMAmers in both AFM and nanowire systems are discussed. The paper also
      provides criteria for evaluation of the sensitivity of fishing-based detection
      systems. The fishing efficiency depending on the detection system parameters is
      estimated. The practical implementation of protein fishing depending on the ratio
      of the sample solution volume and the surface of the detection system is
      discussed. The advantages and disadvantages of today's promising
      nanotechnological protein detection methods implemented on the basis of these
      schemes.

PMID- 25978391
TI  - [Way to the peptide vaccine against hepatitis C].
AB  - In order to surpass the problem of genetic variability of hepatitis C virus
      envelope proteins during vaccine development, we used the so-called "reverse
      vaccinology"approach--"from genome to vaccine". Database of HCV protein sequences
      was designed, viral genome analysis was performed, and several highly conserved
      sites were revealed in HCV envelope proteins in the framework of this approach.
      These sites demonstrated low antigenic activity in full-size proteins and HCV
      virions: antibodies against these sites were not found in all hepatitis C
      patients. However, two sites, which contained a wide set of potential T-helper
      epitope motifs, were revealed among these highly conserved ones. We constructed
      and prepared by solid-phase peptide synthesis several artificial peptide
      constructs composed of two linker-connected highly conserved HCV envelope E2
      protein sites; one of these sites contained a set of T-helper epitope motifs.
      Experiments on laboratory animals demonstrated that the developed peptide
      constructs manifested immunogenicity compared with one of protein molecules and
      were able to raise antibodies, which specifically bound HCV envelope proteins. We
      succeeded in obtaining antibodies reactive with HCV from hepatitis C patient
      plasma upon the immunization with some constructs. An original preparation of a
      peptide vaccine against hepatitis C is under development on the basis of these
      peptide constructs.

PMID- 25978392
TI  - [Computer modelling of monoaminoxidases].
AB  - The article summarized results of studies on active site structures of monoamine
      oxidases (MAO) performed in the Institute of Biomedical Chemistry (Russia) by
      computer modelling approaches. MAO, catalyzing the reaction of oxidative
      deamination of major neurotransmitter monoamines, exists in two highly homologous
      forms, MAO A and MAO B, distinguished by substrate specificity and inhibitor
      selectivity. The development of approaches for active site modelling of these
      enzymes (with unknown three-dimensional structures) started from analysis of
      relationship between the geometrical sizes of rigid indole and isatin derivatives
      and their inhibitory activity. These studies resulted in molding of the active
      site structures of MAO A and MAO B. These molds reflect the sizes and shapes of
      active sites of these enzymes. These mold models have been used for virtual
      screening of molecular databases for new inhibitors. The models obtained at
      different stages of MAO investigations have been compared with recently appeared
      three-dimensional structures of MAO A and MAO B.

PMID- 25978393
TI  - [The possibility of using PlasmaDeepDiveTM MRM panel in clinical diagnostics].
AB  - Concentrations of 46 proteins have been determined in human blood plasma using
      PlasmaDeepDiveTM MRM Panel ("Biognosys AG", Switzerland). 18 of them were
      included into the group of proteins with higher concentrations, also identified
      by the shotgun proteomic analysis. Based on literature data it is concluded that
      the PlasmaDeepDiveTM MRM Panel is applicable for studies of human plasma samples
      for potential biomarkers of various nervous system disorders.

PMID- 25978394
TI  - [Experimental estimation of proteome size for cells and human plasma].
AB  - Huge range of concentrations of different protein and insufficient sensitivity of
      methods for detection of proteins at a single molecule level does not yet allow
      obtaining the whole image of human proteome. In our investigations, we tried to
      evaluate the size of different proteomes (cells and plasma). The approach used is
      based on detection of protein spots in 2-DE after staining by protein dyes with
      different sensitivities. The function representing the dependence of the number
      of protein spots on sensitivity of protein dyes was generated. Next, by
      extrapolation of this function curve to theoretical point of the maximum
      sensitivity (detection of a single smallest polypeptide) it was calculated that a
      single human cell (HepG2) may contain minimum 70,000 proteoforms, and plasma--1.5
      mln. Utilization of this approach to other, smaller proteomes showed the
      competency of this extrapolation. For instance, the size of mycoplas ma
      (Acholeplasma laidlawii) was estimated in 1100 proteoforms, yeast (Saccharomyces
      cerevisiae)--40,000, E. coli--6200, P. furiosus--3400. In hepatocytes, the amount
      of proteoforms was the same as in HepG2--70,000. Significance of obtained data is
      in possibilities to estimating the proteome organization and planning next steps
      in its study.

PMID- 25978395
TI  - [Computer evaluation of hidden potential of phytochemicals of medicinal plants of
      the traditional Indian ayurvedic medicine].
AB  - Applicability of our computer programs PASS and PharmaExpert to prediction of
      biological activity spectra of rather complex and structurally diverse
      phytocomponents of medicinal plants, both separately and in combinations has been
      evaluated. The web-resource on phytochemicals of 50 medicinal plants used in
      Ayurveda was created for the study of hidden therapeutic potential of Traditional
      Indian Medicine (TIM) (http://ayurveda.pharmaexpert.ru). It contains information
      on 50 medicinal plants, their using in TIM and their pharmacology activities,
      also as 1906 phytocomponents. PASS training set was updated by addition of
      information about 946 natural compounds; then the training procedure and
      validation were performed, to estimate the quality of PASS prediction. It was
      shown that the difference between the average accuracy of prediction obtained in
      leave-5%-out cross-validation (94,467%) and in leave-one-out cross-validation
      (94,605%) is very small. These results showed high predictive ability of the
      program. Results of biological activity spectra prediction for all
      phytocomponents included in our database are in good correspondence with the
      experimental data. Additional kinds of biological activity predicted with high
      probability provide the information about most promising directions of further
      studies. The analysis of prediction results of sets of phytocomponents in each of
      50 medicinal plants was made by PharmaExpert software. Based on this analysis, we
      found that the combination of phytocomponents from Passiflora incarnata may
      exhibit nootropic, anticonvulsant and antidepressant effects. Experiments carried
      out in mice models confirmed the predicted effects of Passiflora incarnata
      extracts. 

PMID- 25978396
TI  - Pulmonary function in infants with swallowing dysfunction.
AB  - BACKGROUND: Swallowing dysfunction can lead to recurring aspiration and is
      frequently associated with chronic symptoms such as cough and wheezing in
      infants. Our objective was to describe the characteristics of infants with
      swallowing dysfunction, determine if pulmonary function abnormalities are
      detectable, and if they improve after therapy. METHODS: We studied 38 infants
      with a history of coughing and wheezing who had pulmonary function tests
      performed within two weeks of their diagnosis of swallowing dysfunction. The
      raised lung volume rapid thoracoabdominal compression technique was used. After 6
      months of therapy, 17 of the infants repeated the tests. RESULTS: Initially, 25
      had abnormal spirometry, 18 had abnormal plethysmography, and 15 demonstrated
      bronchodilator responsiveness. Six months later test were repeated for seventeen
      patients. Ten patients had continued abnormal spirometry, two patients remained
      normal, three patients' abnormal spirometry had normalized, and two patients'
      previously normal studies became abnormal. Eight of the 17 patients had continued
      abnormal plethysmography, six had continued normal plethysmography, and three
      patients' normal plethysmography became abnormal. After 6 months of treatment,
      eight patients demonstrated bronchodilator responsiveness, of which five
      continued to demonstrate bronchodilator responsiveness and three developed
      responsiveness. The remainder either continued to be non- bronchodilator
      responsive (two) or lost responsiveness (three.) The findings of the abnormal
      tests in most infants tested is complicated by frequent occurrence of other co
      morbidities in this population, including gastroesophageal reflux in 23 and
      passive smoke exposure in 13 of the infants. CONCLUSIONS: The interpretation of
      lung function changes is complicated by the frequent association of swallowing
      dysfunction with gastroesophageal reflux and passive smoke exposure in this
      population. Six months of medical therapy for swallowing
      dysfunction/gastroesophageal reflux did not significantly improve pulmonary
      function in these infants. Long-term studies will be necessary to determine which
      of these changes persists into adulthood.

PMID- 25978397
TI  - Long-Term Resistance of Drosophila melanogaster to the Mushroom Toxin Alpha
      Amanitin.
AB  - Insect resistance to toxins exerts not only a great impact on our economy, but
      also on the ecology of many species. Resistance to one toxin is often associated
      with cross-resistance to other, sometimes unrelated, chemicals. In this study, we
      investigated mushroom toxin resistance in the fruit fly Drosophila melanogaster
      (Meigen). This fruit fly species does not feed on mushrooms in nature and may
      thus have evolved cross-resistance to alpha-amanitin, the principal toxin of
      deadly poisonous mushrooms, due to previous pesticide exposure. The three Asian
      D. melanogaster stocks used in this study, Ama-KTT, Ama-MI, and Ama-KLM, acquired
      alpha-amanitin resistance at least five decades ago in their natural habitats in
      Taiwan, India, and Malaysia, respectively. Here we show that all three stocks
      have not lost the resistance phenotype despite the absence of selective pressure
      over the past half century. In response to alpha-amanitin in the larval food,
      several signs of developmental retardation become apparent in a concentration
      dependent manner: higher pre-adult mortality, prolonged larva-to-adult
      developmental time, decreased adult body size, and reduced adult longevity. In
      contrast, female fecundity nearly doubles in response to higher alpha-amanitin
      concentrations. Our results suggest that alpha-amanitin resistance has no fitness
      cost, which could explain why the resistance has persisted in all three stocks
      over the past five decades. If pesticides caused alpha-amanitin resistance in D.
      melanogaster, their use may go far beyond their intended effects and have long
      lasting effects on ecosystems. 

PMID- 25978398
TI  - Genetic Diversity of the Hepatitis B Virus Strains in Cuba: Absence of West
      African Genotypes despite the Transatlantic Slave Trade.
AB  - Cuba is an HBsAg low-prevalence country with a high coverage of anti-hepatitis B
      vaccine. Its population is essentially the result of the population mix of
      Spanish descendants and former African slaves. Information about genetic
      characteristics of hepatitis B virus (HBV) strains circulating in the country is
      scarce. The HBV genotypes/subgenotypes, serotypes, mixed infections, and S gene
      mutations of 172 Cuban HBsAg and HBV-DNA positive patients were determined by
      direct sequencing and phylogenetic analysis. Phylogenetic analysis of HBV S gene
      sequences showed a predominance of genotype A (92.4%), subgenotype A2 (84.9%) and
      A1 (7.6%). Genotype D (7.0%) and subgenotype C1 (0.6%) were also detected but
      typical (sub)genotypes of contemporary West-Africa (E, A3) were conspicuously
      absent. All genotype A, D, and C strains exhibited sequence characteristics of
      the adw2, ayw2, and adrq serotypes, respectively. Thirty-three (19.1%) patients
      showed single, double, or multiple point mutations inside the Major Hydrophilic
      domain associated with vaccine escape; eighteen (10.5%) patients had mutations in
      the T-cell epitope (amino acids 28-51), and there were another 111 point
      mutations downstream of the S gene. One patient had an HBV A1/A2 mixed infection.
      This first genetic study of Cuban HBV viruses revealed only strains that were
      interspersed with strains from particularly Europe, America, and Asia. The
      absence of genotype E supports previous hypotheses about an only recent
      introduction of this genotype into the general population in Africa. The presence
      of well-known vaccine escape (3.5%) and viral resistance mutants (2.9%) warrants
      strain surveillance to guide vaccination and treatment strategies. 

PMID- 25978399
TI  - Increased expression of angiogenic and inflammatory proteins in the vitreous of
      patients with ischemic central retinal vein occlusion.
AB  - BACKGROUND: Central retinal vein occlusion (CRVO) is a common disease
      characterized by a disrupted retinal blood supply and a high risk of subsequent
      vision loss due to retinal edema and neovascular disease. This study was designed
      to assess the concentrations of selected signaling proteins in the vitreous and
      blood of patients with ischemic CRVO. METHODS: Vitreous and blood samples were
      collected from patients undergoing surgery for ischemic CRVO (radial optic
      neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n =
      13). Concentrations of 40 different proteins were determined by an ELISA-type
      antibody microarray. RESULTS: Expression of proteins enriched in the vitreous
      (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry
      in eyes of patients with severe ischemic CRVO followed by secondary glaucoma.
      Vitreal expression levels were higher in CRVO patients than in the control group
      (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2),
      HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7),
      IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2)
      (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2
      (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA
      (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression
      of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the
      retina and the retinal pigment epithelium (RPE). CONCLUSION: Proteins related to
      hypoxia, angiogenesis, and inflammation were significantly elevated in the
      vitreous of CRVO patients. Moreover, some markers known to indicate
      atherosclerosis may be related to a basic vascular disease underlying RVO. This
      would imply that local therapeutic targeting might not be sufficient for a long
      term therapy in a systemic disease but hypothetically reduce local changes as an
      initial therapeutic approach.

PMID- 25978400
TI  - Biochemical association of metabolic profile and microbiome in chronic pressure
      ulcer wounds.
AB  - Chronic, non-healing wounds contribute significantly to the suffering of patients
      with co-morbidities in the clinical population with mild to severely compromised
      immune systems. Normal wound healing proceeds through a well-described process.
      However, in chronic wounds this process seems to become dysregulated at the
      transition between resolution of inflammation and re-epithelialization. Bioburden
      in the form of colonizing bacteria is a major contributor to the delayed
      headlining in chronic wounds such as pressure ulcers. However how the microbiome
      influences the wound metabolic landscape is unknown. Here, we have used a Systems
      Biology approach to determine the biochemical associations between the taxonomic
      and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies
      were harvested from primary chronic wounds and bisected into top and bottom
      sections prior to analysis of microbiome by pyrosequencing and analysis of
      metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial
      taxonomy revealed that wounds were colonized predominantly by three main phyla,
      but differed significantly at the genus level. While taxonomic profiles
      demonstrated significant variability between wounds, metabolic profiles shared
      significant similarity based on the depth of the wound biopsy. Biochemical
      association between taxonomy and metabolic landscape indicated significant wound
      to-wound similarity in metabolite enrichment sets and metabolic pathway impacts,
      especially with regard to amino acid metabolism. To our knowledge, this is the
      first demonstration of a statistically robust correlation between bacterial
      colonization and metabolic landscape within the chronic wound environment. 

PMID- 25978401
TI  - Health Behaviors of Breast Cancer Survivors with Hypertension: A Propensity
      Analysis of KNHANES III-V (2005-2012).
AB  - OBJECTIVE: This study examines health behaviors of breast cancer survivors with
      hypertension and compares them with those of non-cancer individuals with
      hypertension. METHODS: In this cross-sectional study, a total of 10,996
      hypertensive adults (>= 19 years) who participated in the 2005-2012 Korean
      National Health and Nutrition Examination Survey (KNHANES) were considered. Data
      on alcohol consumption, smoking, physical activity, antihypertensive medication
      adherence, self-reported diet control, and sodium intake were collected through
      self-report questionnaire. A total of 64 breast cancer survivors with
      hypertension and 10,932 non-cancer participants with hypertension were
      identified. To better compare health behaviors of the two groups, 56 breast
      cancer survivors and 280 non-cancer participants were selected through the 1:5
      nearest available matching based on estimated propensity scores. Multivariate
      analysis was conducted to determine any differences between the two groups.
      RESULTS: According to multivariate analysis, breast cancer survivors with
      hypertension (n = 56) were significantly less likely to consume alcohol (odds
      ratio (OR): 3.75; 95% confidence interval (CI): 1.06-13.29) but significantly
      more likely to have sodium intake of more than 2400 mg (OR: 2.98; 95% CI: 1.27
      6.97) than the propensity-matched control group (n = 280). There was no
      significant difference in other health behaviors between the two groups.
      CONCLUSIONS: Breast cancer survivors require active interventions for healthy
      behaviors related to the management of comorbid conditions such as hypertension
      to reduce the risk of cardiovascular disease and improve their overall survival
      rate.

PMID- 25978402
TI  - Multicomponent interdisciplinary group intervention for self-management of
      fibromyalgia: a mixed-methods randomized controlled trial.
AB  - BACKGROUND: This study evaluated the efficacy of the PASSAGE Program, a
      structured multicomponent interdisciplinary group intervention for the self
      management of FMS. METHODS: A mixed-methods randomized controlled trial
      (intervention (INT) vs. waitlist (WL)) was conducted with patients suffering from
      FMS. Data were collected at baseline (T0), at the end of the intervention (T1),
      and 3 months later (T2). The primary outcome was change in pain intensity (0-10).
      Secondary outcomes were fibromyalgia severity, pain interference, sleep quality,
      pain coping strategies, depression, health-related quality of life, patient
      global impression of change (PGIC), and perceived pain relief. Qualitative group
      interviews with a subset of patients were also conducted. Complete data from T0
      to T2 were available for 43 patients. RESULTS: The intervention had a
      statistically significant impact on the three PGIC measures. At the end of the
      PASSAGE Program, the percentages of patients who perceived overall improvement in
      their pain levels, functioning and quality of life were significantly higher in
      the INT Group (73%, 55%, 77% respectively) than in the WL Group (8%, 12%, 20%).
      The same differences were observed 3 months post-intervention (Intervention
      group: 62%, 43%, 38% vs Waitlist Group: 13%, 13%, 9%). The proportion of patients
      who reported >= 50% pain relief was also significantly higher in the INT Group at
      the end of the intervention (36% vs 12%) and 3 months post-intervention (33% vs
      4%). Results of the qualitative analysis were in line with the quantitative
      findings regarding the efficacy of the intervention. The improvement, however,
      was not reflected in the primary outcome and other secondary outcome measures.
      CONCLUSION: The PASSAGE Program was effective in helping FMS patients gain a
      sense of control over their symptoms. We suggest including PGIC in future
      clinical trials on FMS as they appear to capture important aspects of the
      patients' experience. TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number Register ISRCTN14526380.

PMID- 25978403
TI  - Placental Fatty Acid ethyl esters are elevated with maternal alcohol use in
      pregnancies complicated by prematurity.
AB  - The accumulation of fatty acid ethyl esters (FAEEs) in meconium of term newborns
      has been described as one potential biomarker of maternal alcohol use during
      pregnancy. FAEEs accumulate in multiple alcohol-exposed fetal tissues and in the
      placenta. Limited research has focused on the identification of the premature
      newborn exposed to alcohol in utero. We hypothesized that maternal alcohol use
      occurs in a significant proportion of premature deliveries and that this exposure
      can be detected as elevated placental FAEEs. The goals of this study were to 1)
      determine the prevalence of maternal alcohol use in the premature newborn and 2)
      investigate whether placental FAEEs could identify those newborns with fetal
      alcohol exposure. This prospective observational study evaluated 80 placentas
      from 80 women after premature delivery. Subjects were interviewed for alcohol
      intake and placental FAEEs were quantified via GC/MS. Receiver Operator
      Characteristic (ROC) Curves were generated to evaluate the ability of placental
      FAEEs to predict maternal drinking during pregnancy. Adjusted ROC curves were
      generated to adjust for gestational age, maternal smoking, and illicit drug use.
      30% of the subjects admitted to drinking alcohol during pregnancy and
      approximately 14% answered questions indicative of problem drinking (designated
      AUDIT+). The specific FAEEs ethyl stearate and linoleate, as well as combinations
      of oleate + linoleate + linolenate (OLL) and of OLL + stearate, were
      significantly (p<0.05) elevated in placentas from AUDIT+ pregnancies. Adjusted
      ROC Curves generated areas under the curve ranging from 88-93% with negative
      predictive values of 97% for AUDIT+ pregnancies. We conclude that nearly one
      third of premature pregnancies were alcohol-exposed, and that elevated placental
      FAEEs hold great promise to accurately determine maternal alcohol use,
      particularly heavy use, in pregnancies complicated by premature delivery. 

PMID- 25978404
TI  - Expression of prostate-specific membrane antigen in lung cancer cells and tumor
      neovasculature endothelial cells and its clinical significance.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA) has been found in tumor
      neovasculature endothelial cells (NECs) of non-prostate cancers and may become
      the most promising target for anti-tumor therapy. To study the value of PSMA as a
      potential new target for lung cancer treatment, PSMA expression in non-small cell
      lung cancer (NSCLC) and small cell lung cancer (SCLC) tissues and its
      relationship with clinicopathology were investigated in the current study.
      METHODS: Immunohistochemistry was used to detect PSMA expression in a total of
      150 lung specimens of patients with lung cancer. The data were analyzed using
      univariate and multivariate statistical analyses. RESULTS: The percentages of
      NSCLC patients who had PSMA (+) tumor cells and PSMA (+) NECs were 54.02% and
      85.06%, respectively. The percentage of patients younger than 60 years old who
      had PSMA (+) tumor cells was 69.05%, which was significantly greater than the
      percentage of patients aged 60 years or older (40.00%, p<0.05). A significant
      difference was observed in the percentage of NSCLC patients with PMSA (+) NECs
      and stage I or II cancer (92.98%) and those patients with stage III or IV cancer
      (76.77%). In the SCLC tissues, NEC PSMA expression (70.00%) did not differ
      significantly from NSCLC. SCLC tumor cells and normal lung tissues cells were all
      negative. There was no significant correlation between the presence of PSMA (+)
      NECs in SCLC patients and the observed clinicopathological parameters.
      CONCLUSIONS: PSMA is expressed not only in NECs of NSCLC and SCLC but also in
      tumor cells of most NSCLC patients. The presence of PSMA (+) tumor cells and PSMA
      (+) NECs in NSCLC was negatively correlated with age and the clinicopathological
      stage of the patients, respectively.

PMID- 25978405
TI  - Acidification reduced growth rate but not swimming speed of larval sea urchins.
AB  - Swimming behaviors of planktonic larvae impact dispersal and population dynamics
      of many benthic marine invertebrates. This key ecological function is modulated
      by larval development dynamics, biomechanics of the resulting morphology, and
      behavioral choices. Studies on ocean acidification effects on larval stages have
      yet to address this important interaction between development and swimming under
      environmentally-relevant flow conditions. Our video motion analysis revealed that
      pH covering present and future natural variability (pH 8.0, 7.6 and 7.2) did not
      affect age-specific swimming of larval green urchin Strongylocentrotus
      droebachiensis in still water nor in shear, despite acidified individuals being
      significantly smaller in size (reduced growth rate). This maintenance of speed
      and stability in shear was accompanied by an overall change in size-corrected
      shape, implying changes in swimming biomechanics. Our observations highlight
      strong evolutionary pressure to maintain swimming in a varying environment and
      the plasticity in larval responses to environmental change. 

PMID- 25978406
TI  - Free-roaming dog population estimation and status of the dog population
      management and rabies control program in Dhaka City, Bangladesh.
AB  - Beginning January 2012, a humane method of dog population management using a
      Catch-Neuter-Vaccinate-Release (CNVR) program was implemented in Dhaka City,
      Bangladesh as part of the national rabies control program. To enable this
      program, the size and distribution of the free-roaming dog population needed to
      be estimated. We present the results of a dog population survey and a pilot
      assessment of the CNVR program coverage in Dhaka City. Free-roaming dog
      population surveys were undertaken in 18 wards of Dhaka City on consecutive days
      using mark-resight methods. Data was analyzed using Lincoln-Petersen index
      Chapman correction methods. The CNVR program was assessed over the two years
      (2012-2013) whilst the coverage of the CNVR program was assessed by estimating
      the proportion of dogs that were ear-notched (processed dogs) via dog population
      surveys. The free-roaming dog population was estimated to be 1,242 (95 % CI: 1205
      1278) in the 18 sampled wards and 18,585 dogs in Dhaka City (52 dogs/km2) with an
      estimated human-to-free-roaming dog ratio of 828:1. During the two year CNVR
      program, a total of 6,665 dogs (3,357 male and 3,308 female) were neutered and
      vaccinated against rabies in 29 of the 92 city wards. A pilot population survey
      indicated a mean CNVR coverage of 60.6% (range 19.2-79.3%) with only eight wards
      achieving > 70% coverage. Given that the coverage in many neighborhoods was below
      the WHO-recommended threshold level of 70% for rabies eradications and since the
      CNVR program takes considerable time to implement throughout the entire Dhaka
      City area, a mass dog vaccination program in the non-CNVR coverage area is
      recommended to create herd immunity. The findings from this study are expected to
      guide dog population management and the rabies control program in Dhaka City and
      elsewhere in Bangladesh. 

PMID- 25978407
TI  - Lower Breast Cancer Risk among Women following the World Cancer Research Fund and
      American Institute for Cancer Research Lifestyle Recommendations: EpiGEICAM Case
      Control Study.
AB  - BACKGROUND: According to the "World Cancer Research Fund" and the "American
      Institute of Cancer Research" (WCRF/AICR) one in four cancer cases could be
      prevented through a healthy diet, weight control and physical activity.
      OBJECTIVE: To explore the association between the WCRF/AICR recommendations and
      risk of breast cancer. METHODS: During the period 2006 to 2011 we recruited 973
      incident cases of breast cancer and 973 controls from 17 Spanish Regions. We
      constructed a score based on 9 of the WCRF/AICR recommendations for cancer
      prevention:: 1)Maintain adequate body weight; 2)Be physically active; 3)Limit the
      intake of high density foods; 4)Eat mostly plant foods; 5)Limit the intake of
      animal foods; 6)Limit alcohol intake; 7)Limit salt and salt preserved food
      intake; 8)Meet nutritional needs through diet; S1)Breastfeed infants exclusively
      up to 6 months. We explored its association with BC by menopausal status and by
      intrinsic tumor subtypes (ER+/PR+ & HER2-; HER2+; ER&PR-&HER2-) using conditional
      and multinomial logistic models respectively. RESULTS: Our results point to a
      linear association between the degree of noncompliance and breast cancer risk.
      Taking women who met 6 or more recommendations as reference, those meeting less
      than 3 showed a three-fold excess risk (OR=2.98(CI95%:1.59-5.59)), especially for
      postmenopausal women (OR=3.60(CI95%:1.24;10.47)) and ER+/PR+&HER2-
      (OR=3.60(CI95%:1.84;7.05)) and HER2+ (OR=4.23(CI95%:1.66;10.78)) tumors.
      Noncompliance of recommendations regarding the consumption of foods and drinks
      that promote weight gain in premenopausal women (OR=2.24(CI95%:1.18;4.28); p for
      interaction=0.014) and triple negative tumors (OR=2.93(CI95%:1.12-7.63)); the
      intake of plant foods in postmenopausal women (OR=2.35(CI95%:1.24;4.44)) and
      triple negative tumors (OR=3.48(CI95%:1.46-8.31)); and the alcohol consumption in
      ER+/PR+&HER2- tumors (OR=1.52 (CI95%:1.06-2.19)) showed the strongest
      associations. CONCLUSION: Breast cancer prevention might be possible by following
      the "World Cancer Research Fund" and the "American Institute of Cancer Research"
      recommendations, even in settings like Spain, where a high percentage of women
      already comply with many of them.

PMID- 25978408
TI  - Cell elasticity is regulated by the tropomyosin isoform composition of the actin
      cytoskeleton.
AB  - The actin cytoskeleton is the primary polymer system within cells responsible for
      regulating cellular stiffness. While various actin binding proteins regulate the
      organization and dynamics of the actin cytoskeleton, the proteins responsible for
      regulating the mechanical properties of cells are still not fully understood. In
      the present study, we have addressed the significance of the actin associated
      protein, tropomyosin (Tpm), in influencing the mechanical properties of cells.
      Tpms belong to a multi-gene family that form a co-polymer with actin filaments
      and differentially regulate actin filament stability, function and organization.
      Tpm isoform expression is highly regulated and together with the ability to sort
      to specific intracellular sites, result in the generation of distinct Tpm isoform
      containing actin filament populations. Nanomechanical measurements conducted with
      an Atomic Force Microscope using indentation in Peak Force Tapping in
      indentation/ramping mode, demonstrated that Tpm impacts on cell stiffness and the
      observed effect occurred in a Tpm isoform-specific manner. Quantitative analysis
      of the cellular filamentous actin (F-actin) pool conducted both biochemically and
      with the use of a linear detection algorithm to evaluate actin structures
      revealed that an altered F-actin pool does not absolutely predict changes in cell
      stiffness. Inhibition of non-muscle myosin II revealed that intracellular tension
      generated by myosin II is required for the observed increase in cell stiffness.
      Lastly, we show that the observed increase in cell stiffness is partially
      recapitulated in vivo as detected in epididymal fat pads isolated from a Tpm3.1
      transgenic mouse line. Together these data are consistent with a role for Tpm in
      regulating cell stiffness via the generation of specific populations of Tpm
      isoform-containing actin filaments. 

PMID- 25978410
TI  - Characterization of Insertion Sequence ISSau2 in the Human and Livestock
      Associated Staphylococcus aureus.
AB  - Mobile genetic elements play important roles in evolution and diversification of
      bacterial genomes. ISSau2 is 1660bp in length with terminal 5'-TG and CA-3'
      dinucleotides and has two overlapping reading frames orfA and orfB. It has been
      found in a wide range of S. aureus, such as HA-MRSA252, LGA251, MRSA S0385 and
      ED133. To determine distribution of ISSau2, 164 S. aureus isolates from milk
      samples of mastitic cows from our laboratory and all the S. aureus strains from
      the National Center for Biotechnology Information (NCBI) database were screened
      for the presence of ISSau2. Next, in order to explore a potential relationship
      among S. aureus ISSau2-containing strains and isolates, a relationship among 10
      ISSau2-positive S. aureus isolates and 27 ISSau2-positive S. aureus strains was
      investigated by a phylogenetic analysis. These ISSau2 isolates and strains could
      be classified into four groups (A, B, C and D). The strains or isolates in Group
      D were all isolated from mammary glands, suggesting tissue specificity. All
      strains in Group B had an identical ISSau2 derivative, termed ISSau21628, with
      32bp deletion at the 3' terminus. ISSau21628 in strain ST398 from Group B was
      closely related to ISSau2 in strain LGA251 from Group D. 

PMID- 25978409
TI  - Promotion of bone morphogenetic protein signaling by tetraspanins and
      glycosphingolipids.
AB  - Bone morphogenetic proteins (BMPs) belong to the transforming growth factor beta
      (TGFbeta) superfamily of secreted molecules. BMPs play essential roles in
      multiple developmental and homeostatic processes in metazoans. Malfunction of the
      BMP pathway can cause a variety of diseases in humans, including cancer, skeletal
      disorders and cardiovascular diseases. Identification of factors that ensure
      proper spatiotemporal control of BMP signaling is critical for understanding how
      this pathway is regulated. We have used a unique and sensitive genetic screen to
      identify the plasma membrane-localized tetraspanin TSP-21 as a key new factor in
      the C. elegans BMP-like "Sma/Mab" signaling pathway that controls body size and
      postembryonic M lineage development. We showed that TSP-21 acts in the signal
      receiving cells and genetically functions at the ligand-receptor level. We
      further showed that TSP-21 can associate with itself and with two additional
      tetraspanins, TSP-12 and TSP-14, which also promote Sma/Mab signaling. TSP-12 and
      TSP-14 can also associate with SMA-6, the type I receptor of the Sma/Mab pathway.
      Finally, we found that glycosphingolipids, major components of the tetraspanin
      enriched microdomains, are required for Sma/Mab signaling. Our findings suggest
      that the tetraspanin-enriched membrane microdomains are important for proper BMP
      signaling. As tetraspanins have emerged as diagnostic and prognostic markers for
      tumor progression, and TSP-21, TSP-12 and TSP-14 are all conserved in humans, we
      speculate that abnormal BMP signaling due to altered expression or function of
      certain tetraspanins may be a contributing factor to cancer development. 

PMID- 25978412
TI  - Correction: The Carboxy-Terminal Domain of Erb1 Is a Seven-Bladed beta-Propeller
      that Binds RNA.

PMID- 25978411
TI  - Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome.
AB  - The inflammasome is a molecular platform that stimulates the activation of
      caspase-1 and the processing of pro-interleukin (IL)-1beta and pro-IL-18 for
      secretion. The NOD-like receptor family, pyrin domain containing 3 (NLRP3)
      protein is activated by diverse molecules and pathogens, leading to the formation
      of the NLRP3 inflammasome. Recent studies showed that the NLRP3 inflammasome
      mediates innate immunity against influenza A virus (IAV) infection. In this
      study, we investigated the function of the IAV non-structural protein 1 (NS1) in
      the modulation of NLRP3 inflammasome. We found that NS1 proteins derived from
      both highly pathogenic and low pathogenic strains efficiently decreased secretion
      of IL-1beta and IL-18 from THP-1 cells treated with LPS and ATP. NS1
      overexpression significantly impaired the transcription of proinflammatory
      cytokines by inhibiting transactivation of the nuclear factor-kappaB (NF-kappaB),
      a major transcription activator. Furthermore, NS1 physically interacted with
      endogenous NLRP3 and activation of the NLRP3 inflammasome was abrogated in NS1
      expressing THP-1 cells. These findings suggest that NS1 downregulates NLRP3
      inflammasome activation by targeting NLRP3 as well as NF-kappaB, leading to a
      reduction in the levels of inflammatory cytokines as a viral immune evasion
      strategy. 

PMID- 25978413
TI  - Sleep disorders in patients with cancer.
AB  - Sleep disturbances are common among patients with cancer for many reasons. Sleep
      problems can be present at any stage during treatment for cancer and in some
      patients, sleep disturbance may be the presenting symptoms that lead to the
      diagnosis of some types of cancer. Poor sleep impairs quality of life In people
      with cancer, but most do not specifically complain of sleep problems unless they
      are explicitly asked. Insomnia and fatigue are most common sleep disorders in
      this cohort, although primary sleep disorders, including obstructive sleep apnea
      and restless legs syndrome, which are common in the general population, have not
      been carefully studied in the oncology setting despite significant impairment to
      their quality of life. 

PMID- 25978414
TI  - Age and Gender Variations in Cancer Diagnostic Intervals in 15 Cancers: Analysis
      of Data from the UK Clinical Practice Research Datalink.
AB  - BACKGROUND: Time from symptomatic presentation to cancer diagnosis (diagnostic
      interval) is an important, and modifiable, part of the patient's cancer pathway,
      and can be affected by various factors such as age, gender and type of presenting
      symptoms. The aim of this study was to quantify the relationships of diagnostic
      interval with these variables in 15 cancers diagnosed between 2007 and 2010 using
      routinely collected data from the Clinical Practice Research Datalink (CPRD) in
      the UK. METHODS: Symptom lists for each cancer were prepared from the literature
      and by consensus amongst the clinician researchers, which were then categorised
      into either NICE qualifying (NICE) or not (non-NICE) based on NICE Urgent
      Referral Guidelines for Suspected Cancer criteria. Multivariable linear
      regression models were fitted to examine the relationship between diagnostic
      interval (outcome) and the predictors: age, gender and symptom type. RESULTS:
      18,618 newly diagnosed cancer patients aged >=40 who had a recorded symptom in
      the preceding year were included in the analysis. Mean diagnostic interval was
      greater for older patients in four disease sites (difference in days per 10 year
      increase in age; 95% CI): bladder (10.3; 5.5 to 15.1; P<0.001), kidney (11.0; 3.4
      to 18.6; P=0.004), leukaemia (18.5; 8.8 to 28.1; P<0.001) and lung (10.1; 6.7 to
      13.4; P<0.001). There was also evidence of longer diagnostic interval in older
      patients with colorectal cancer (P<0.001). However, we found that mean diagnostic
      interval was shorter with increasing age in two cancers: gastric (-5.9; -11.7 to 
      0.2; P=0.04) and pancreatic (-6.0; -11.2 to -0.7; P=0.03). Diagnostic interval
      was longer for females in six of the gender non-specific cancers (mean difference
      in days; 95% CI): bladder (12.2; 0.8 to 23.6; P=0.04), colorectal (10.4; 4.3 to
      16.5; P=0.001), gastric (14.3; 1.1 to 27.6; P=0.03), head and neck (31.3; 6.2 to
      56.5; P=0.02), lung (8.0; 1.2 to 14.9; P=0.02), and lymphoma (19.2; 3.8 to 34.7;
      P=0.01). Evidence of longer diagnostic interval was found for patients presenting
      with non-NICE symptoms in 10 of 15 cancers (mean difference in days; 95% CI):
      bladder (62.9; 48.7 to 77.2; P<0.001), breast (115.1; 105.9 to 124.3; P<0.001),
      cervical (60.3; 31.6 to 89.0; P<0.001), colorectal (25.8; 19.6 to 31.9; P<0.001),
      gastric (24.1; 3.4 to 44.8; P=0.02), kidney (22.1; 4.5 to 39.7; P=0.01),
      oesophageal (67.0; 42.1 to 92.0; P<0.001), pancreatic (48.6; 28.1 to 69.1;
      P<0.001), testicular (36.7; 17.0 to 56.4; P< 0.001), and endometrial (73.8; 60.3
      to 87.3; P<0.001). Pooled analysis across all cancers demonstrated highly
      significant evidence of differences overall showing longer diagnostic intervals
      with increasing age (7.8 days; 6.4 to 9.1; P<0.001); for females (8.9 days; 5.5
      to 12.2; P<0.001); and in non-NICE symptoms (27.7 days; 23.9 to 31.5; P<0.001).
      CONCLUSIONS: We found age and gender-specific inequalities in time to diagnosis
      for some but not all cancer sites studied. Whilst these need further explanation,
      these findings can inform the development and evaluation of interventions
      intended to achieve timely diagnosis and improved cancer outcomes, such as to
      provide equity across all age and gender groupings.

PMID- 25978415
TI  - A metabolomic study on the responses of daphnia magna exposed to silver nitrate
      and coated silver nanoparticles.
AB  - We examined the short-term toxicity of AgNPs and AgNO3 to Daphnia magna at
      sublethal levels using (1)H NMR-based metabolomics. Two sizes of
      polyvinylpyrrolidone-coated AgNPs (10 and 40nm) were synthesized and
      characterized and their Ag(+) release was studied using centrifugal
      ultrafiltration and inductively coupled plasma mass spectrometry. Multivariate
      statistical analysis of the (1)H NMR spectra showed significant changes in the D.
      magna metabolic profiles following 48h exposure to both AgNP particle sizes and
      Ag(+) exposure. Most of the metabolic biomarkers for AgNP exposure, including 3
      hydroxybutyrate, arginine, lysine and phosphocholine, were identical to those of
      the Ag(+)-exposed groups, suggesting that the dominant effects of both AgNPs were
      due to released Ag(+). The observed metabolic changes implied that the released
      Ag(+) induced disturbance in energy metabolism and oxidative stress, a proposed
      mechanism of AgNP toxicity. Elevated levels of lactate in all AgNP-treated but
      not in Ag(+)-treated groups provided evidence for Ag-NP enhanced anaerobic
      metabolism. These findings show that (1)H NMR-based metabolomics provides a
      sensitive measure of D. magna response to AgNPs and that further targeted assays
      are needed to elucidate mechanisms of action of nanoparticle-induced toxicity. 

PMID- 25978416
TI  - Computational Identification of Antigenicity-Associated Sites in the
      Hemagglutinin Protein of A/H1N1 Seasonal Influenza Virus.
AB  - The antigenic variability of influenza viruses has always made influenza vaccine
      development challenging. The punctuated nature of antigenic drift of influenza
      virus suggests that a relatively small number of genetic changes or combinations
      of genetic changes may drive changes in antigenic phenotype. The present study
      aimed to identify antigenicity-associated sites in the hemagglutinin protein of
      A/H1N1 seasonal influenza virus using computational approaches. Random Forest
      Regression (RFR) and Support Vector Regression based on Recursive Feature
      Elimination (SVR-RFE) were applied to H1N1 seasonal influenza viruses and used to
      analyze the associations between amino acid changes in the HA1 polypeptide and
      antigenic variation based on hemagglutination-inhibition (HI) assay data. Twenty
      three and twenty antigenicity-associated sites were identified by RFR and SVR
      RFE, respectively, by considering the joint effects of amino acid residues on
      antigenic drift. Our proposed approaches were further validated with the H3N2
      dataset. The prediction models developed in this study can quantitatively predict
      antigenic differences with high prediction accuracy based only on HA1 sequences.
      Application of the study results can increase understanding of H1N1 seasonal
      influenza virus antigenic evolution and accelerate the selection of vaccine
      strains. 

PMID- 25978417
TI  - Barriers in referring neonatal patients to perinatal palliative care: a French
      multicenter survey.
AB  - BACKGROUND: When an incurable fetal condition is detected, some women (or
      couples) would rather choose to continue with the pregnancy than opt for
      termination of pregnancy for medical reasons, which, in France, can be performed
      until full term. Such situations are frequently occurring and sometimes leading
      to the implementation of neonatal palliative care. The objectives of this study
      were to evaluate the practices of perinatal care french professionals in this
      context; to identify the potential obstacles that might interfere with the
      provision of an appropriate neonatal palliative care; and, from an opposite
      perspective, to determine the criteria that led, in some cases, to offer this
      type of care for prenatally diagnosed lethal abnormality. METHODS: We used an
      email survey sent to 434 maternal-fetal medicine specialists (MFMs) and fetal
      care pediatric specialists (FCPs) at 48 multidisciplinary centers for prenatal
      diagnosis (MCPD). RESULTS: Forty-two multidisciplinary centers for prenatal
      diagnosis (87.5%) took part. In total, 102 MFMs and 112 FCPs completed the
      survey, yielding response rate of 49.3%. One quarter of professionals (26.2%)
      estimated that over 20% of fetal pathologies presenting in MCPD could correspond
      to a diagnosis categorized as lethal (FCPs versus MFMs: 24% vs 17.2%, p = 0.04).
      The mean proportion of fetal abnormalities eligible for palliative care at birth
      was estimated at 19.30% (+/- 2.4) (FCPs versus MFMs: 23.4% vs 15.2%, p = 0.029).
      The degree of diagnostic certainty appears to be the most influencing factor
      (98.1%, n = 207) in the information provided to the pregnant woman with regard to
      potential neonatal palliative care. The vast majority of professionals, 92.5%,
      supported considering the practice of palliative care as a regular option to
      propose antenatally. CONCLUSIONS: Our study reveals the clear need for training
      perinatal professionals in perinatal palliative care and for the standardization
      of practices in this field.

PMID- 25978418
TI  - Motivation-focused thinking: Buffering against stress-related physical symptoms
      and depressive symptomology.
AB  - Developmental transitions are experienced throughout the life course and
      necessitate adapting to consequential and unpredictable changes that can
      undermine health. Our six-month study (n = 239) explored whether selective
      secondary control striving (motivation-focused thinking) protects against the
      elevated levels of stress and depressive symptoms increasingly common to young
      adults navigating the challenging school-to-university transition. Path analyses
      supplemented with tests of moderated mediation revealed that, for young adults
      who face challenging obstacles to goal attainment, selective secondary control
      indirectly reduced long-term stress-related physical and depressive symptoms
      through selective primary control and previously unexamined measures of discrete
      emotions. Results advance the existing literature by demonstrating that (a)
      selective secondary control has health benefits for vulnerable young adults and
      (b) these benefits are largely a consequence of the process variables proposed in
      Heckhausen et al.'s (2010) theory. 

PMID- 25978419
TI  - Personalized mortality prediction driven by electronic medical data and a patient
      similarity metric.
AB  - BACKGROUND: Clinical outcome prediction normally employs static, one-size-fits
      all models that perform well for the average patient but are sub-optimal for
      individual patients with unique characteristics. In the era of digital
      healthcare, it is feasible to dynamically personalize decision support by
      identifying and analyzing similar past patients, in a way that is analogous to
      personalized product recommendation in e-commerce. Our objectives were: 1) to
      prove that analyzing only similar patients leads to better outcome prediction
      performance than analyzing all available patients, and 2) to characterize the
      trade-off between training data size and the degree of similarity between the
      training data and the index patient for whom prediction is to be made. METHODS
      AND FINDINGS: We deployed a cosine-similarity-based patient similarity metric
      (PSM) to an intensive care unit (ICU) database to identify patients that are most
      similar to each patient and subsequently to custom-build 30-day mortality
      prediction models. Rich clinical and administrative data from the first day in
      the ICU from 17,152 adult ICU admissions were analyzed. The results confirmed
      that using data from only a small subset of most similar patients for training
      improves predictive performance in comparison with using data from all available
      patients. The results also showed that when too few similar patients are used for
      training, predictive performance degrades due to the effects of small sample
      sizes. Our PSM-based approach outperformed well-known ICU severity of illness
      scores. Although the improved prediction performance is achieved at the cost of
      increased computational burden, Big Data technologies can help realize
      personalized data-driven decision support at the point of care. CONCLUSIONS: The
      present study provides crucial empirical evidence for the promising potential of
      personalized data-driven decision support systems. With the increasing adoption
      of electronic medical record (EMR) systems, our novel medical data analytics
      contributes to meaningful use of EMR data.

PMID- 25978421
TI  - Structural rearrangement in the aqueous solution of surface active ionic liquid 1
      butyl-3-methylimidazolium bis(2-ethylhexyl) sulfosuccinate.
AB  - The aggregation behaviors of surface active ionic liquid 1-butyl-3
      methylimidazolium bis(2-ethylhexyl) sulfosuccinate in aqueous solutions were
      investigated by conductometry, densimetry, fluorimetry, (1)H nuclear magnetic
      resonance ((1)H NMR) spectroscopy, dynamic light scattering (DLS), and
      transmission electron microscopy (TEM), which confirmed two distinguished
      critical concentrations. The first critical concentration was believed to be the
      critical aggregation concentration (CAC), where two different types of aggregates
      were formed, namely, micelles with the size of 10 nm and vesicles with the size
      of 100 nm. The second critical concentration at two-fold CAC was suggested to be
      resulting from the insertion of the imidazolium cations into aggregates. 

PMID- 25978420
TI  - Diagnostic ability of macular ganglion cell inner plexiform layer measurements in
      glaucoma using swept source and spectral domain optical coherence tomography.
AB  - PURPOSE: To evaluate the diagnostic ability of macular ganglion cell and inner
      plexiform layer measurements in glaucoma, obtained using swept source (SS) and
      spectral domain (SD) optical coherence tomography (OCT) and to compare to
      circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements.
      METHODS: The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of
      22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular
      ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex
      (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under
      the receiver operating characteristic curves (AUCs) were calculated to determine
      ability to differentiate glaucomatous and healthy eyes and between early
      glaucomatous and healthy eyes. RESULTS: Mean (+/- standard deviation) mGCIPL and
      mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT
      compared to using SD-OCT. Fixed and proportional biases were detected between SS
      OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between
      healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS
      OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired
      using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than
      for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75,
      respectively) but these differences did not consistently reach statistical
      significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT)
      had the highest AUC (0.86) among macular measurements. CONCLUSION: Assessment of
      mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous
      damage, but measurements are not interchangeable for patient management
      decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT
      were similar to that of cpRNFL for glaucoma detection.

PMID- 25978422
TI  - Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia
      coli Infection: Genomic Case-Control Studies.
AB  - BACKGROUND: Typical enteropathogenic Escherichia coli (tEPEC) strains were
      associated with mortality in the Global Enteric Multicenter Study (GEMS). Genetic
      differences in tEPEC strains could underlie some of the variability in clinical
      outcome. METHODS: We produced draft genome sequences of all available tEPEC
      strains from GEMS lethal infections (LIs) and of closely matched EPEC strains
      from GEMS subjects with non-lethal symptomatic infections (NSIs) and asymptomatic
      infections (AIs) to identify gene clusters (potential protein encoding sequences
      sharing >=90% nucleotide sequence identity) associated with lethality. RESULTS:
      Among 14,412 gene clusters identified, the presence or absence of 392 was
      associated with clinical outcome. As expected, more gene clusters were associated
      with LI versus AI than LI versus NSI. The gene clusters more prevalent in strains
      from LI than those from NSI and AI included those encoding proteins involved in O
      antigen biogenesis, while clusters encoding type 3 secretion effectors EspJ and
      OspB were among those more prevalent in strains from non-lethal infections. One
      gene cluster encoding a variant of an NleG ubiquitin ligase was associated with
      LI versus AI, while two other nleG clusters had the opposite association. Similar
      associations were found for two nleG gene clusters in an additional, larger
      sample of NSI and AI GEMS strains. CONCLUSIONS: Particular genes are associated
      with lethal tEPEC infections. Further study of these factors holds potential to
      unravel the mechanisms underlying severe disease and to prevent adverse outcomes.

PMID- 25978423
TI  - Phosphate Homeostasis in Conditions of Phosphate Proficiency and Limitation in
      the Wild Type and the phoP Mutant of Streptomyces lividans.
AB  - Phosphate, as a constituent of the high energy molecules, ATP/GTP and
      polyphosphate, plays a crucial role in most of the metabolic processes of living
      organisms. Therefore, the adaptation to low Pi availability is a major challenge
      for bacteria. In Streptomyces, this adaptation is tightly controlled by the two
      component PhoR/PhoP system. In this study, the free intracellular Pi, ATP, ADP
      and polyP content of the wild type and the phoP mutant strain of S. lividans TK24
      were analyzed at discrete time points throughout growth in Pi replete and limited
      media. PolyP length and content was shown to be directly related to the Pi
      content of the growth medium. In Pi repletion, ATP and high molecular weight
      (HMW) polyP contents were higher in the phoP mutant than in the WT strain. This
      supports the recently proposed repressive effect of PhoP on oxidative
      phosphorylation. High oxidative phosphorylation activity might also have a direct
      or indirect positive impact on HMW polyP synthesis. In Pi sufficiency as in Pi
      limitation, the degradation of these polymers was shown to be clearly delayed in
      the phoP mutant, indicating PhoP dependent expression of the enzymes involved in
      this degradation. The efficient storage of Pi as polyphosphate and/or its
      inefficient degradation in Pi in the phoP mutant resulted in low levels of free
      Pi and ATP that are likely to be, at least in part, responsible for the very poor
      growth of this mutant in Pi limitation. Furthermore, short polyP was shown to be
      present outside the cell, tightly bound to the mycelium via electrostatic
      interactions involving divalent cations. Less short polyP was found to be
      associated with the mycelium of the phoP mutant than with that of the WT strain,
      indicating that generation and externalization of these short polyP molecules was
      directly or indirectly dependent on PhoP. 

PMID- 25978424
TI  - Cell Cycle Control by the Master Regulator CtrA in Sinorhizobium meliloti.
AB  - In all domains of life, proper regulation of the cell cycle is critical to
      coordinate genome replication, segregation and cell division. In some groups of
      bacteria, e.g. Alphaproteobacteria, tight regulation of the cell cycle is also
      necessary for the morphological and functional differentiation of cells.
      Sinorhizobium meliloti is an alphaproteobacterium that forms an economically and
      ecologically important nitrogen-fixing symbiosis with specific legume hosts.
      During this symbiosis S. meliloti undergoes an elaborate cellular differentiation
      within host root cells. The differentiation of S. meliloti results in massive
      amplification of the genome, cell branching and/or elongation, and loss of
      reproductive capacity. In Caulobacter crescentus, cellular differentiation is
      tightly linked to the cell cycle via the activity of the master regulator CtrA,
      and recent research in S. meliloti suggests that CtrA might also be key to
      cellular differentiation during symbiosis. However, the regulatory circuit
      driving cell cycle progression in S. meliloti is not well characterized in both
      the free-living and symbiotic state. Here, we investigated the regulation and
      function of CtrA in S. meliloti. We demonstrated that depletion of CtrA cause
      cell elongation, branching and genome amplification, similar to that observed in
      nitrogen-fixing bacteroids. We also showed that the cell cycle regulated
      proteolytic degradation of CtrA is essential in S. meliloti, suggesting a
      possible mechanism of CtrA depletion in differentiated bacteroids. Using a
      combination of ChIP-Seq and gene expression microarray analysis we found that
      although S. meliloti CtrA regulates similar processes as C. crescentus CtrA, it
      does so through different target genes. For example, our data suggest that CtrA
      does not control the expression of the Fts complex to control the timing of cell
      division during the cell cycle, but instead it negatively regulates the septum
      inhibiting Min system. Our findings provide valuable insight into how highly
      conserved genetic networks can evolve, possibly to fit the diverse lifestyles of
      different bacteria. 

PMID- 25978425
TI  - Identification and Characterization of MicroRNAs in Ginkgo biloba var. epiphylla
      Mak.
AB  - Ginkgo biloba, a dioecious plant known as a living fossil, is an ancient
      gymnosperm that stands distinct from other gymnosperms and angiosperms. Ginkgo
      biloba var. epiphylla (G. biloba var. epiphylla), with ovules borne on the leaf
      blade, is an unusual germplasm derived from G. biloba. MicroRNAs (miRNAs) are
      post-transcriptional gene regulators that play critical roles in diverse
      biological and metabolic processes. Currently, little is known about the miRNAs
      involved in the key stage of partly epiphyllous ovule germination in G. biloba
      var. epiphylla. Two small RNA libraries constructed from epiphyllous ovule leaves
      and normal leaves of G. biloba var. epiphylla were sequenced on an
      Illumina/Solexa platform. A total of 82 miRNA sequences belonging to 23 families
      and 53 putative novel miRNAs were identified in the two libraries. Differential
      expression analysis showed that 25 conserved and 21 novel miRNAs were
      differentially expressed between epiphyllous ovule leaves and normal leaves. The
      expression patterns of partially differentially expressed miRNAs and the
      transcript levels of their predicted target genes were validated by quantitative
      real time RT-PCR. All the expression profiles of the 21 selected miRNAs were
      similar to those detected by Solexa deep sequencing. Additionally, the transcript
      levels of almost all the putative target genes of 9 selected miRNAs were opposite
      to those of the corresponding miRNAs. The putative target genes of the
      differentially expressed miRNAs were annotated with Gene Ontology terms related
      to reproductive process, metabolic process and responding to stimulus. This work
      presents a broad range of small RNA transcriptome data obtained from epiphyllous
      ovule and normal leaves of G. biloba var. epiphylla, which may provide insights
      into the miRNA-mediated regulation in the epiphyllous ovule germination process. 

PMID- 25978427
TI  - Expenditure Analysis of HIV Testing and Counseling Services Using the Cascade
      Framework in Vietnam.
AB  - OBJECTIVES: Currently, HIV testing and counseling (HTC) services in Vietnam are
      primarily funded by international sources. However, international funders are now
      planning to withdraw their support and the Government of Vietnam (GVN) is seeking
      to identify domestic funding and generate client fees to continue services. A
      clear understanding of the cost to sustain current HTC services is becoming
      increasingly important to facilitate planning that can lead to making HTC and
      other HIV services more affordable and sustainable in Vietnam. The objectives of
      this analysis were to provide a snapshot of current program costs to achieve key
      program outcomes including 1) testing and identifying PLHIV unaware of their HIV
      status and 2) successfully enrolling HIV (+) clients in care. METHODS: We
      reviewed expenditure data reported by 34 HTC sites in nine Vietnamese provinces
      over a one-year period from October 2012 to September 2013. Data on program
      outcomes were extracted from the HTC database of 42,390 client records. Analysis
      was carried out from the service providers' perspective. RESULTS: The mean
      expenditure for a single client provided HTC services (testing, receiving results
      and referral for care/treatment) was US $7.6. The unit expenditure per PLHIV
      identified through these services varied widely from US $22.8 to $741.5 (median:
      $131.8). Excluding repeat tests, the range for expenditure to newly diagnose a
      PLHIV was even wider (from US $30.8 to $1483.0). The mean expenditure for one
      successfully referred HIV client to care services was US $466.6. Personnel costs
      contributed most to the total cost. CONCLUSIONS: Our analysis found a wide range
      of expenditures by site for achieving the same outcomes. Re-designing systems to
      provide services at the lowest feasible cost is essential to making HIV services
      more affordable and treatment for prevention programs feasible in Vietnam. The
      analysis also found that understanding the determinants and reasons for variance
      in service costs by site is an important enhancement to the cascade of HIV
      services framework now adapted for and extensively used in Vietnam for planning
      and evaluation.

PMID- 25978426
TI  - A Population Based Study of the Genetic Association between Catecholamine Gene
      Variants and Spontaneous Low-Frequency Fluctuations in Reaction Time.
AB  - The catecholamines dopamine and noradrenaline have been implicated in spontaneous
      low-frequency fluctuations in reaction time, which are associated with attention
      deficit hyperactivity disorder (ADHD) and subclinical attentional problems. The
      molecular genetic substrates of these behavioral phenotypes, which reflect
      frequency ranges of intrinsic neuronal oscillations (Slow-4: 0.027-0.073 Hz; Slow
      5: 0.010-0.027 Hz), have not yet been investigated. In this study, we performed
      regression analyses with an additive model to examine associations between low
      frequency fluctuations in reaction time during a sustained attention task and
      genetic markers across 23 autosomal catecholamine genes in a large young adult
      population cohort (n = 964), which yielded greater than 80% power to detect a
      small effect size (f(2) = 0.02) and 100% power to detect a small/medium effect
      size (f(2) = 0.15). At significance levels corrected for multiple comparisons,
      none of the gene variants were associated with the magnitude of low-frequency
      fluctuations. Given the study's strong statistical power and dense coverage of
      the catecholamine genes, this either indicates that associations between low
      frequency fluctuation measures and catecholamine gene variants are absent or that
      they are of very small effect size. Nominally significant associations were
      observed between variations in the alpha-2A adrenergic receptor gene (ADRA2A) and
      the Slow-5 band. This is in line with previous reports of an association between
      ADRA2A gene variants and general reaction time variability during response
      selection tasks, but the specific association of these gene variants and low
      frequency fluctuations requires further confirmation. Pharmacological challenge
      studies could in the future provide convergent evidence for the noradrenergic
      modulation of both general and time sensitive measures of intra-individual
      variability in reaction time.

PMID- 25978428
TI  - Sugar Sweetened Beverage Consumption among Adults with Gout or Type 2 Diabetes.
AB  - BACKGROUND: Current guidelines for the management of type 2 diabetes and gout
      recommend that people with these conditions limit their sugar sweetened beverage
      (SSB) intake. We examined self-reported SSB intake among New Zealand adults with
      gout or type 2 diabetes, including those on hemodialysis. METHOD: 1023 adults
      with gout and 580 adults (including 206 receiving hemodialysis) with type 2
      diabetes, participated in this study of between 2009 and 2012. Participants
      completed an interviewer-administered SSB intake question "how many sugar
      sweetened drinks (including fruit juice), but not including diet drinks, do you
      normally drink per day?" SSB consumption was recorded as a circled number 0, 1,
      2, 3, 4, 5, or >5, cans or large glasses (300 mL) per day. RESULTS: Consuming one
      or more SSB per day was reported by 64% (622/1023) of subjects with gout, 49%
      (176/374) with type 2 diabetes without dialysis, and 47% (96/206) with diabetes
      on dialysis. Consuming four or more SSBs per day was reported by 18% (179/1023),
      9% (31/374) and 9% (18/206), respectively. Such high consumers of SSB were
      characterized after multivariable analysis to be more likely to be male (adjusted
      odds ratio (OR) 1.8; 95% confidence interval 1.1-2.9), younger in age (40 vs 65
      years: 1.6; 1.1-2.3), current smoker (5.2; 2.7-10.1), obese (BMI 41 vs 26
      kg/m(2): 1.4; 1-1.9), and report Maori (1.8; 1.2-2.8) or Pacific (1.6; 1.1-2.5)
      ancestry, compared to Caucasian. People with gout were more likely to report
      heavy SSB intake compared to people with diabetes (OR 2.4, 95% CI 1.5-3.9). Heavy
      SSB consumption reported by people with diabetes was similar if they did or did
      not require dialysis. CONCLUSION: A high proportion of patients with gout and
      type 2 diabetes, including those on haemodialysis, are not responding to health
      messages to abstain from SSB consumption.

PMID- 25978429
TI  - Non-rainfall moisture activates fungal decomposition of surface litter in the
      Namib Sand Sea.
AB  - The hyper-arid western Namib Sand Sea (mean annual rainfall 0-17 mm) is a
      detritus-based ecosystem in which primary production is driven by large, but
      infrequent rainfall events. A diverse Namib detritivore community is sustained by
      minimal moisture inputs from rain and fog. The decomposition of plant material in
      the Namib Sand Sea (NSS) has long been assumed to be the province of these
      detritivores, with beetles and termites alone accounting for the majority of
      litter losses. We have found that a mesophilic Ascomycete community, which
      responds within minutes to moisture availability, is present on litter of the
      perennial Namib dune grass Stipagrostis sabulicola. Important fungal traits that
      allow survival and decomposition in this hyper-arid environment with intense
      desiccation, temperature and UV radiation stress are darkly-pigmented hyphae, a
      thermal range that includes the relatively low temperature experienced during fog
      and dew, and an ability to survive daily thermal and desiccation stress at
      temperatures as high as 50 degrees C for five hours. While rainfall is very
      limited in this area, fog and high humidity provide regular periods (>= 1 hour)
      of sufficient moisture that can wet substrates and hence allow fungal growth on
      average every 3 days. Furthermore, these fungi reduce the C/N ratio of the litter
      by a factor of two and thus detritivores, like the termite Psammotermes
      allocerus, favor fungal-infected litter parts. Our studies show that despite the
      hyper-aridity of the NSS, fungi are a key component of energy flow and
      biogeochemical cycling that should be accounted for in models addressing how the
      NSS ecosystem will respond to projected climate changes which may alter
      precipitation, dew and fog regimes. 

PMID- 25978430
TI  - Correction: Secondary Hyperalgesia Phenotypes Exhibit Differences in Brain
      Activation during Noxious Stimulation.

PMID- 25978431
TI  - NPM-ALK mediates phosphorylation of MSH2 at tyrosine 238, creating a functional
      deficiency in MSH2 and the loss of mismatch repair.
AB  - The vast majority of anaplastic lymphoma kinase-positive anaplastic large cell
      lymphoma (ALK+ALCL) tumors express the characteristic oncogenic fusion protein
      NPM-ALK, which mediates tumorigenesis by exerting its constitutive tyrosine
      kinase activity on various substrates. We recently identified MSH2, a protein
      central to DNA mismatch repair (MMR), as a novel binding partner and
      phosphorylation substrate of NPM-ALK. Here, using liquid chromatography-mass
      spectrometry, we report for the first time that MSH2 is phosphorylated by NPM-ALK
      at a specific residue, tyrosine 238. Using GP293 cells transfected with NPM-ALK,
      we confirmed that the MSH2(Y238F) mutant is not tyrosine phosphorylated.
      Furthermore, transfection of MSH2(Y238F) into these cells substantially decreased
      the tyrosine phosphorylation of endogenous MSH2. Importantly, gene transfection
      of MSH2(Y238F) abrogated the binding of NPM-ALK with endogenous MSH2, re
      established the dimerization of MSH2:MSH6 and restored the sensitivity to DNA
      mismatch-inducing drugs, indicative of MMR return. Parallel findings were
      observed in two ALK+ALCL cell lines, Karpas 299 and SUP-M2. In addition, we found
      that enforced expression of MSH2(Y238F) into ALK+ALCL cells alone was sufficient
      to induce spontaneous apoptosis. In conclusion, our findings have identified NPM
      ALK-induced phosphorylation of MSH2 at Y238 as a crucial event in suppressing
      MMR. Our studies have provided novel insights into the mechanism by which
      oncogenic tyrosine kinases disrupt MMR. 

PMID- 25978432
TI  - Rational combination treatment with histone deacetylase inhibitors and
      immunomodulatory drugs in multiple myeloma.
AB  - Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide
      trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and
      thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi)
      also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger
      significant MM cell growth inhibition by inhibiting or downregulating c-Myc.
      Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic
      acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity,
      associated with downregulation of c-Myc. Unexpectedly, we observed that decreased
      levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by
      these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len
      shows less efficacy than simultaneous treatment with this combination.
      Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs,
      together with Len induces synergistic MM cytotoxicity without alteration of CRBN
      expression. Our results showed that only modest class-I HDAC inhibition is able
      to induce synergistic MM cytotoxicity in combination with Len. These studies may
      provide the framework for utilizing HDACi in combination with Len to both avoid
      CRBN downregulation and enhance anti-MM activities. 

PMID- 25978433
TI  - The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic
      cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells.
AB  - Epigenetic modifying enzymes have a crucial role in the pathogenesis of acute
      myeloid leukemia (AML). Methylation of lysine 9 on histone H3 by the
      methyltransferase G9a and SUV39H1 is associated with inhibition of tumor
      suppressor genes. We studied the effect of G9a and SUV39H1 inhibitors on
      viability and differentiation of AML cells and tested the cytotoxicity induced by
      combination of G9a and SUV39H1 inhibitors and various epigenetic drugs. The
      SUV39H1 inhibitor (chaetocin) and the G9a inhibitor (UNC0638) caused cell death
      in AML cells at high concentrations. However, only chaetocin-induced CD11b
      expression and differentiation of AML cells at non-cytotoxic concentration. HL-60
      and KG-1a cells were more sensitive to chaetocin than U937 cells. Long-term
      incubation of chaetocin led to downregulation of SUV39H1 and reduction of H3K9
      tri-methylation in HL-60 and KG-1a cells. Combination of chaetocin with
      suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor) or JQ (a
      BET (bromodomain extra terminal) bromodomain inhibitor) showed synergistic
      cytotoxicity. Conversely, no synergism was found by combining chaetocin and
      UNC0638. More importantly, chaetocin-induced differentiation and combined
      cytotoxicity were also found in the primary cells of AML patients. Collectively,
      the SUV39H1 inhibitor chaetocin alone or in combination with other epigenetic
      drugs may be effective for the treatment of AML. 

PMID- 25978434
TI  - A novel MYD88 mutation, L265RPP, in Waldenstrom macroglobulinemia activates the
      NF-kappaB pathway to upregulate Bcl-xL expression and enhances cell survival.

PMID- 25978435
TI  - A New Family of HEAT-Like Repeat Proteins Lacking a Critical Substrate
      Recognition Motif Present in Related DNA Glycosylases.
AB  - DNA glycosylases are important repair enzymes that eliminate a diverse array of
      aberrant nucleobases from the genomes of all organisms. Individual bacterial
      species often contain multiple paralogs of a particular glycosylase, yet the
      molecular and functional distinctions between these paralogs are not well
      understood. The recently discovered HEAT-like repeat (HLR) DNA glycosylases are
      distributed across all domains of life and are distinct in their specificity for
      cationic alkylpurines and mechanism of damage recognition. Here, we describe a
      number of phylogenetically diverse bacterial species with two orthologs of the
      HLR DNA glycosylase AlkD. One ortholog, which we designate AlkD2, is
      substantially less conserved. The crystal structure of Streptococcus mutans AlkD2
      is remarkably similar to AlkD but lacks the only helix present in AlkD that
      penetrates the DNA minor groove. We show that AlkD2 possesses only weak DNA
      binding affinity and lacks alkylpurine excision activity. Mutational analysis of
      residues along this DNA binding helix in AlkD substantially reduced binding
      affinity for damaged DNA, for the first time revealing the importance of this
      structural motif for damage recognition by HLR glycosylases. 

PMID- 25978436
TI  - Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa.
AB  - Transient receptor potential ankyrin1 (TRPA1) and transient receptor potential
      vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related,
      nonselective cation channels and mediators of several signaling pathways.
      Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy
      against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1
      activators in Agastache rugosa (Fisch. et Meyer) O. Kuntze (A.rugosa), commonly
      known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem
      and leaves of A.rugosa (Labiatae) selectively activated hTRPA1 and hTRPV1. We
      next investigated the effects of commercially available compounds found in
      A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L
      carveol, beta-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol,
      pachypodol, and rosmarinic acid) on cultured hTRPA1- and hTRPV1-expressing cells.
      Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4
      allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values
      of 189.1+/-26.8, 29.8+/-14.9, 160.2+/-21.9, 1535+/-315.7, and 546.5+/-73.0 MUM,
      respectively. The activities of these compounds were effectively inhibited by the
      hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active
      compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2+/
      1.4 MUM), our results suggest that these compounds from the stem and leaves of
      A.rugosa are specific and selective agonists of hTRPA1. 

PMID- 25978437
TI  - Compensatory UTE/T2W Imaging of Inflammatory Vascular Wall in Hyperlipidemic
      Rabbits.
AB  - OBJECTIVES: To obtain compensatory ultra-short echo time (UTE) imaging and T2
      weighted (T2W) imaging of Watanabe heritable hyperlipidemic (WHHL) rabbits
      following dextran-coated magnetic nanocluster (DMNC) injection for the effective
      in vivo detection of inflammatory vascular wall. METHODS: Magnetic nanoparticle
      was synthesized by thermal decomposition and encapsulated with dextran to prepare
      DMNC. The contrast enhancement efficiency of DMNC was investigated using UTE
      (repetition time [TR] = 5.58 and TE = 0.07 ms) and T2W (TR = 4000 and TE = 60 ms)
      imaging sequences. To confirm the internalization of DMNC into macrophages, DMNC
      treated macrophages were visualized by cellular transmission electron microscope
      (TEM) and magnetic resonance (MR) imaging. WHHL rabbits expressing macrophage
      rich plaques were subjected to UTE and T2W imaging before and after intravenous
      DMNC (120 MUmol Fe/kg) treatment. Ex vivo MR imaging of plaques and
      immunostaining studies were also performed. RESULTS: Positive and negative
      contrast enhancement of DMNC solutions with increasing Fe concentrations were
      observed in UTE and T2W imaging, respectively. The relative signal intensities of
      the DMNC solution containing 2.9 mM Fe were calculated as 3.53 and 0.99 in UTE
      and T2W imaging, respectively. DMNC uptake into the macrophage cytoplasm was
      visualized by electron microscopy. Cellular MR imaging of DMNC-treated
      macrophages revealed relative signals of 3.00 in UTE imaging and 0.98 in T2W
      imaging. In vivo MR images revealed significant brightening and darkening of
      plaque areas in the WHHL rabbit 24 h after DMNC injection in UTE and T2W imaging,
      respectively. Ex vivo MR imaging results agreed with these in vivo MR imaging
      results. Histological analysis showed that DMNCs were localized to areas of
      inflammatory vascular wall. CONCLUSIONS: Using compensatory UTE and T2W imaging
      in conjunction with DMNC is an effective approach for the noninvasive in vivo
      imaging of atherosclerotic plaque.

PMID- 25978438
TI  - An Official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for
      Potentially Inappropriate Treatments in Intensive Care Units.
AB  - BACKGROUND: There is controversy about how to manage requests by patients or
      surrogates for treatments that clinicians believe should not be administered.
      PURPOSE: This multisociety statement provides recommendations to prevent and
      manage intractable disagreements about the use of such treatments in intensive
      care units. METHODS: The recommendations were developed using an iterative
      consensus process, including expert committee development and peer review by
      designated committees of each of the participating professional societies
      (American Thoracic Society, American Association for Critical Care Nurses,
      American College of Chest Physicians, European Society for Intensive Care
      Medicine, and Society of Critical Care). MAIN RESULTS: The committee recommends:
      (1) Institutions should implement strategies to prevent intractable treatment
      conflicts, including proactive communication and early involvement of expert
      consultants. (2) The term "potentially inappropriate" should be used, rather than
      futile, to describe treatments that have at least some chance of accomplishing
      the effect sought by the patient, but clinicians believe that competing ethical
      considerations justify not providing them. Clinicians should explain and advocate
      for the treatment plan they believe is appropriate. Conflicts regarding
      potentially inappropriate treatments that remain intractable despite intensive
      communication and negotiation should be managed by a fair process of conflict
      resolution; this process should include hospital review, attempts to find a
      willing provider at another institution, and opportunity for external review of
      decisions. When time pressures make it infeasible to complete all steps of the
      conflict-resolution process and clinicians have a high degree of certainty that
      the requested treatment is outside accepted practice, they should seek procedural
      oversight to the extent allowed by the clinical situation and need not provide
      the requested treatment. (3) Use of the term "futile" should be restricted to the
      rare situations in which surrogates request interventions that simply cannot
      accomplish their intended physiologic goal. Clinicians should not provide futile
      interventions. (4) The medical profession should lead public engagement efforts
      and advocate for policies and legislation about when life-prolonging technologies
      should not be used. CONCLUSIONS: The multisociety statement on responding to
      requests for potentially inappropriate treatments in intensive care units
      provides guidance for clinicians to prevent and manage disputes in patients with
      advanced critical illness.

PMID- 25978439
TI  - Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential
      model of retinopathy of prematurity.
AB  - Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a
      leading cause of infantile blindness worldwide. Retinopathy of prematurity is
      caused by the failure of central retinal vessels to reach the retinal periphery,
      creating a nonperfused peripheral retina, resulting in retinal hypoxia,
      neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of
      vision. We established a potential retinopathy of prematurity model by using a
      green fluorescent vascular endothelium zebrafish transgenic line treated with
      cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular
      endothelial growth factor inducer) at 24 hours postfertilization, and observed
      that the number of vascular branches and sprouts significantly increased in the
      central retinal vascular trunks 2-4 days after treatment. We created an
      angiography method by using tetramethylrhodamine dextran, which exhibited severe
      vascular leakage through the vessel wall into the surrounding retinal tissues.
      The quantification of mRNA extracted from the heads of the larvae by using real
      time quantitative polymerase chain reaction revealed a twofold increase in vegfaa
      and vegfr2 expression compared with the control group, indicating increased
      vascular endothelial growth factor signaling in the hypoxic condition. In
      addition, we demonstrated that the hypoxic insult could be effectively rescued by
      several antivascular endothelial growth factor agents such as SU5416,
      bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly
      reproducible, and clinically relevant retinopathy of prematurity model based on
      zebrafish embryos; this model may serve as a useful platform for clarifying the
      mechanisms of human retinopathy of prematurity and its progression. 

PMID- 25978440
TI  - Colorimetric detection of clinical DNA samples using an intercalator-conjugated
      polydiacetylene sensor.
AB  - We herein developed a novel colorimetric polydiacetylene (PDA) sensor for very
      convenient detection of clinical DNA samples based on the interaction between an
      intercalator and dsDNA. We modified the terminal carboxyl group of a diacetylene
      monomer (10,12-pentacosadiynoic acid; PCDA) with the intercalator 9-aminoacridine
      (9AA) and prepared 9AA-modified PDA liposomes containing PCDA
      9AA/PCDA/phospholipid (1,2-dimyristoyl-rac-glycero-3-phosphocholine) at a molar
      ratio of 1.5:6.5:2.0. The PDA sensor underwent an obvious color transition from
      blue to red in the presence of dsDNA molecules that were PCR-amplified from
      genomic DNA due to the insertion of the 9AA head group of PDA into the dsDNA. DNA
      concentrations as low as 20 nM and relatively small molecules (around 100 base
      pairs) could be detected by the sensor within 1h without DNA electrophoresis.
      This novel colorimetric method is simple, does not require any instrument, and is
      therefore appropriate for POCT or portable molecular diagnostic kit.

PMID- 25978441
TI  - A novel dynamic flow immunochromatographic test (DFICT) using gold nanoparticles
      for the serological detection of Toxoplasma gondii infection in dogs and cats.
AB  - A novel dynamic flow immunochromatographic test (DFICT) is proposed for rapid
      assay utilizing Toxoplasma gondii as a model. The test is based on a proprietary
      technology that combines the principles of immunochromatography and fluid
      dynamics. Gold nanoparticles conjugated to staphylococcal protein A (SPA) were
      prepared in liquid form and used as signal vehicles. T. gondii-specific
      recombinant antigens and SPA were sprayed onto a nitrocellulose membrane in
      strips at positions designated as T and C, respectively. The DFICT is performed
      by applying a 100 uL aliquot of liquid gold-SPA conjugate to the reagent hole and
      a 5 MUL aliquot of serum sample to the sample hole. The results were observable
      within 5 min by the naked eye. The lowest detectable limit of the assay was
      determined as the highest dilution (1:320) of positive serum. No cross-reaction
      of the antibodies with other related canine or feline pathogens was observed. The
      DFICT can be stored for 12 months at 4 degrees C or 6 months with no loss of
      sensitivity or specificity. A high degree of consistency was observed between the
      DFICT and the standard ELISA kit, supporting the reliability of the novel test
      strip. The introduction of a liquid gold nanoparticle conjugate reagent provides
      this method with several attractive characteristics, such as ease of manufacture,
      low sample volume requirements, high selectivity and high efficiency. This method
      opens a novel pathway for rapid diagnostic screening and field analysis.

PMID- 25978442
TI  - Development of quantum dots-based biosensor towards on-farm detection of
      subclinical ketosis.
AB  - Early detection of dairy animal health issues allows the producer or veterinarian
      to intervene before the animals' production levels, or even survival, is
      threatened. An increased concentration of beta-hydroxybutyrate (betaHBA) is a key
      biomarker for diagnosis of subclinical ketosis (SCK), and provides information on
      the health stress in cows well before any external symptoms are observable. In
      this study, quantum dots (QDs) modified with cofactor nicotinamide adenine
      dinucleotide (NAD(+)) were prepared for the sensing event, by which the betaHBA
      concentration in the cow's blood and milk samples was determined via fluorescence
      analysis of the functionalized QDs. The detection was performed on a custom
      designed microfluidic platform combining with a low cost and miniaturized optical
      sensor. The sensing mechanism was first validated by a microplate reader method
      and then applied to the microfluidic platform. Standard betaHBA solution, betaHBA
      in blood and milk samples from cows were successfully measured by this novel
      technology with a detection limit at a level of 35 uM. Side by side comparison of
      the developed microfluidic biosensor with a commercial kit presented its good
      performance.

PMID- 25978443
TI  - Silicon/SU8 multi-electrode micro-needle for in vivo neurochemical monitoring.
AB  - Simultaneous monitoring of glucose and lactate is an important challenge for
      understanding brain energetics in physiological or pathological states. We
      demonstrate here a versatile method based on a minimally invasive single
      implantation in the rat brain. A silicon/SU8-polymer multi-sensing needle-shaped
      biosensor, was fabricated and tested. The multi-electrode array design comprises
      three platinum planar microelectrodes with a surface area of 40 * 200 um(2) and a
      spacing of 200 um, which were micromachined on a single 3mm long micro-needle
      having a 100 * 50 um(2) cross-section for reduced tissue damage during
      implantation. Platinum micro-electrodes were aligned at the bottom of micro-wells
      obtained by photolithography on a SU8 photoresist layer. After clean room
      processing, each micro-electrode was functionalized inside the micro-wells by
      means of a micro-dispensing device, either with glucose oxidase or with lactate
      oxidase, which were cross-linked on the platinum electrodes. The third electrode
      covered with Bovine Serum Albumin (BSA) was used for the control of non-specific
      currents. The thick SU8 photoresist layer has revealed excellent electrical
      insulation of the micro-electrodes and between interconnection lines, and ensured
      a precise localization and packaging of the sensing enzymes on platinum micro
      electrodes. During in vitro calibration with concentrations of analytes in the mM
      range, the micro-wells patterned in the SU8 photoresist proved to be highly
      effective in eliminating cross-talk signals, caused by H2O2 diffusion from
      closely spaced micro-electrodes. Moreover, our biosensor was successfully assayed
      in the rat cortex for simultaneous monitoring of both glucose and lactate during
      insulin and glucose administration.

PMID- 25978444
TI  - A longitudinal, observational study with many repeated measures demonstrated
      improved precision of individual survival curves using Bayesian joint modeling of
      disability and survival.
AB  - BACKGROUND/STUDY CONTEXT: It has not been previously demonstrated whether
      Bayesian joint modeling (BJM) of disability and survival can, under certain
      conditions, improve precision of individual survival curves. METHODS: A
      longitudinal, observational study wherein 754 initially nondisabled community
      dwelling adults in greater New Haven, Connecticut, were observed on a monthly
      basis for over 10 years. RESULTS: In this study, BJM exploited many monthly
      observations to demonstrate, relative to a separate survival model with
      adjustment, improved precision of individual survival curves, permitting
      detection of significant differences between survival curves of two similar
      individuals. The gain in precision was lost when using only those observations
      from intervals of 6, 9, or 12 months. CONCLUSION: When there are many repeated
      measures, BJM of longitudinal functional disability and interval-censored
      survival can potentially increase the precision of individual survival curves
      relative to those from a separate survival model. This may facilitate the
      identification of significant differences between individual survival curves, a
      useful result usually precluded by the large variability inherent to individual
      level estimates from stand-alone survival models.

PMID- 25978445
TI  - Trajectories of disability and their relationship with health status and social
      service use.
AB  - BACKGROUND/STUDY CONTEXT: This longitudinal study was conducted between 1994 and
      2004 in a cohort of southern Taiwan community-living older residents. The study
      aims to explore the trajectories of disability and how these patterns differed
      between respondents who survived and those who died during data collection
      phases; this study also investigated how health status change and social service
      use predicted the different trajectories of disability. METHODS: Disability,
      chronic disease, depression, and social service usage data were collected over
      six waves. Clusters of disability were used to define a categorical response
      variable. Baseline levels and new occurrences of chronic disease and depression
      and the frequency of social service use during this period were chosen as the
      predictors of disability trajectories. RESULTS: Changes in levels of disability
      during the aging process were identified. Different trajectories clearly
      reflected heterogeneity within disability clusters and between surviving and
      nonsurviving respondents. This study highlighted that hypertension and depression
      were predictors of increased disability among both surviving and nonsurviving
      respondents, whereas diabetes was only found to be a strong predictor of
      increased disability for the nonsurviving respondents. In addition, this study
      found that use of social services such as personal care, homemaker-household, and
      physical therapy were significantly associated with an increase in disability,
      whereas use of recreational services seemed to be associated with a decrease in
      disability. CONCLUSIONS: These findings identify disability to be a highly
      dynamic process, which can be characterized into different trajectory clusters
      (e.g., no, mild, and major disability clusters). A greater awareness of these
      trajectories could be used to better target strategies to prevent and/or manage
      disabilities in an aging population.

PMID- 25978446
TI  - Negative arousal increases the effects of stimulus salience in older adults.
AB  - BACKGROUND/STUDY CONTEXT: Stimuli compete for mental representation, with salient
      stimuli attracting more attention than less salient stimuli. In a recent study,
      we found that presenting an emotionally negative arousing sound before briefly
      showing an array of letters with different levels of salience increased the
      reporting of the more salient letters but decreased reporting of the less salient
      letters (Sutherland & Mather, 2012, Emotion, 12, 1367-1372). In the current study
      we examined whether negative arousal produces similar effects on attention in
      older adults. METHODS: Data from 55 older adults (61-80 years; M = 70.7, SD =
      5.1) were compared with those from 110 younger adults (18-29 years; M = 20.3, SD
      = 2.3) from Sutherland and Mather (2012). Neutral or negative arousing sound
      clips were played before a brief presentation of eight letters, three of which
      were presented in a darker font than the others to create a group of high- and
      low-salience targets. Next, participants recalled as many of the letters as they
      could. At the end of the study, participants rated the emotional arousal and the
      valence of the sounds. RESULTS: Higher ratings of emotional arousal for the
      sounds predicted a greater advantage for high-salience letters in recall. This
      influence of arousal did not significantly differ by age. CONCLUSION: The effects
      of negative arousal on subsequent attention were similar in older adults as in
      younger adults. Moreover, the results support arousal-biased competition theory
      (Mather & Sutherland, 2011, Perspectives on Psychological Science, 6, 114-133),
      which predicts that emotional arousal amplifies the effects of stimulus salience
      in attention and memory.

PMID- 25978448
TI  - The influence of aging on outgroup stereotypes: the mediating role of cognitive
      and motivational facets of deficient flexibility.
AB  - BACKGROUND/STUDY CONTEXT: The current study was designed to examine previously
      reported findings about age-related changes in drawing stereotypic inferences;
      specifically, that older adults are more likely than younger adults to stereotype
      outgroup members. The study replicates previous research and extends it by
      exploring the cognitive and motivational facets of deficient flexibility
      underlying this effect and comparing stereotypes towards ingroup and outgroup
      members. METHODS: In the experiment, younger and older adults read stories that
      allowed for stereotypic inferences. They also completed the Trail Making Test
      (TMT) and Need for Closure Scale (NFC) as cognitive and motivational measures of
      deficient flexibility. RESULTS: The results of the experiment revealed that,
      compared to younger participants, older adults were more likely to rely upon
      stereotypic inferences when they read a story about outgroup members; however,
      there were no age-group differences in using stereotypes when they read a story
      about ingroup members. In addition, the findings showed that making more
      stereotypical inferences by older versus younger adults in relation to outgroup
      members was mediated by cognitive (TMT) and motivational (NFC) facets of
      deficient flexibility. CONCLUSION: A major implication of these findings is that
      both cognitive and motivational facets of deficient flexibility contribute to the
      reliance of older adults on stereotypes compared with younger adults. However,
      this is only true when older adults process information about outgroup members,
      but not about ingroup members. Thus, the current research goes beyond previous
      results by providing direct evidence that ingroup-outgroup perception contributes
      to stereotyping among older participants.

PMID- 25978447
TI  - The effect of plausibility on sentence comprehension among older adults and its
      relation to cognitive functions.
AB  - BACKGROUND/STUDY CONTEXT: Older adults show age-related decline in complex
      sentence comprehension. This has been attributed to a decrease in cognitive
      abilities that may support language processing, such as working memory (e.g.,
      Caplan, DeDe, Waters, & Michaud, 2011,Psychology and Aging, 26, 439-450). The
      authors examined whether older adults have difficulty comprehending semantically
      implausible sentences and whether specific executive functions contribute to
      their comprehension performance. METHODS: Forty-two younger adults (aged 18-35)
      and 42 older adults (aged 55-75) were tested on two experimental tasks: a
      multiple negative comprehension task and an information processing battery.
      RESULTS: Both groups, older and younger adults, showed poorer performance for
      implausible sentences than for plausible sentences; however, no interaction was
      found between plausibility and age group. A regression analysis revealed that
      inhibition efficiency, as measured by a task that required resistance to
      proactive interference, predicted comprehension of implausible sentences in older
      adults only. Consistent with the compensation hypothesis, the older adults with
      better inhibition skills showed better comprehension than those with poor
      inhibition skills. CONCLUSION: The findings suggest that semantic implausibility,
      along with syntactic complexity, increases linguistic and cognitive processing
      loads on auditory sentence comprehension. Moreover, the contribution of
      inhibitory control to the processing of semantic plausibility, particularly among
      older adults, suggests that the relationship between cognitive ability and
      language comprehension is strongly influenced by age.

PMID- 25978449
TI  - Non-illness-related factors contributing to traffic safety in older drivers: a
      literature review.
AB  - BACKGROUND/STUDY CONTEXT: Older drivers are at increased risk of becoming
      involved in car crashes. Contrary to well-studied illness-related factors
      contributing to crash risk, the non-illness-related factors that can influence
      safety of older drivers are underresearched. METHODS: Here, the authors review
      the literature on non-illness-related factors influencing driving in people over
      age 60. We identified six safety-relevant factors: road infrastructure, vehicle
      characteristics, traffic-related knowledge, accuracy of self-awareness,
      personality traits, and self-restricted driving. RESULTS: The literature suggests
      that vehicle preference, the quality of traffic-related knowledge, the location
      and time of traffic exposure, and personality traits should all be taken into
      account when assessing fitness-to-drive in older drivers. Studies indicate that
      self-rating of driving skills does not reliably predict fitness-to-drive.
      CONCLUSIONS: Most factors discussed are adaptable or accessible to training and
      collectively may have the potential to increase traffic safety for older drivers
      and other road users.

PMID- 25978450
TI  - bHLH106 Integrates Functions of Multiple Genes through Their G-Box to Confer Salt
      Tolerance on Arabidopsis.
AB  - An activation-tagging methodology was applied to dedifferentiated calli of
      Arabidopsis to identify new genes involved in salt tolerance. This identified
      salt tolerant callus 8 (stc8) as a gene encoding the basic helix-loop-helix
      transcription factor bHLH106. bHLH106-knockout (KO) lines were more sensitive to
      NaCl, KCl, LiCl, ABA, and low temperatures than the wild-type. Back
      transformation of the KO line rescued its phenotype, and over-expression (OX) of
      bHLH106 in differentiated plants exhibited tolerance to NaCl. Green fluorescent
      protein (GFP) fused with bHLH106 revealed that it was localized to the nucleus.
      Prepared bHLH106 protein was subjected to electrophoresis mobility shift assays
      against E-box sequences (5'-CANNTG-3'). The G-box sequence 5'-CACGTG-3' had the
      strongest interaction with bHLH106. bHLH106-OX lines were transcriptomically
      analyzed, and resultant up- and down-regulated genes selected on the criterion of
      presence of a G-box sequence. There were 198 genes positively regulated by
      bHLH106 and 36 genes negatively regulated; these genes possessed one or more G
      box sequences in their promoter regions. Many of these genes are known to be
      involved in abiotic stress response. It is concluded that bHLH106 locates at a
      branching point in the abiotic stress response network by interacting directly to
      the G-box in genes conferring salt tolerance on plants. 

PMID- 25978451
TI  - Transcriptome sequencing of two phenotypic mosaic Eucalyptus trees reveals large
      scale transcriptome re-modelling.
AB  - Phenotypic mosaic trees offer an ideal system for studying differential gene
      expression. We have investigated two mosaic eucalypt trees from two closely
      related species (Eucalyptus melliodora and E. sideroxylon), which each support
      two types of leaves: one part of the canopy is resistant to insect herbivory and
      the remaining leaves are susceptible. Driving this ecological distinction are
      differences in plant secondary metabolites. We used these phenotypic mosaics to
      investigate genome wide patterns of foliar gene expression with the aim of
      identifying patterns of differential gene expression and the somatic mutation(s)
      that lead to this phenotypic mosaicism. We sequenced the mRNA pool from leaves of
      the resistant and susceptible ecotypes from both mosaic eucalypts using the
      Illumina HiSeq 2000 platform. We found large differences in pathway regulation
      and gene expression between the ecotypes of each mosaic. The expression of the
      genes in the MVA and MEP pathways is reflected by variation in leaf chemistry,
      however this is not the case for the terpene synthases. Apart from the terpene
      biosynthetic pathway, there are several other metabolic pathways that are
      differentially regulated between the two ecotypes, suggesting there is much more
      phenotypic diversity than has been described. Despite the close relationship
      between the two species, they show large differences in the global patterns of
      gene and pathway regulation. 

PMID- 25978452
TI  - Gut Microbiota Dynamics during Dietary Shift in Eastern African Cichlid Fishes.
AB  - The gut microbiota structure reflects both a host phylogenetic history and a
      signature of adaptation to the host ecological, mainly trophic niches. African
      cichlid fishes, with their array of closely related species that underwent a
      rapid dietary niche radiation, offer a particularly interesting system to explore
      the relative contribution of these two factors in nature. Here we surveyed the
      host intra- and interspecific natural variation of the gut microbiota of five
      cichlid species from the monophyletic tribe Perissodini of lake Tanganyika, whose
      members transitioned from being zooplanktivorous to feeding primarily on fish
      scales. The outgroup riverine species Astatotilapia burtoni, largely omnivorous,
      was also included in the study. Fusobacteria, Firmicutes and Proteobacteria
      represented the dominant components in the gut microbiota of all 30 specimens
      analysed according to two distinct 16S rRNA markers. All members of the
      Perissodini tribe showed a homogenous pattern of microbial alpha and beta
      diversities, with no significant qualitative differences, despite changes in
      diet. The recent diet shift between zooplantkon- and scale-eaters simply reflects
      on a significant enrichment of Clostridium taxa in scale-eaters where they might
      be involved in the scale metabolism. Comparison with the omnivorous species A.
      burtoni suggests that, with increased host phylogenetic distance and/or
      increasing herbivory, the gut microbiota begins differentiating also at
      qualitative level. The cichlids show presence of a large conserved core of taxa
      and a small set of core OTUs (average 13-15%), remarkably stable also in
      captivity, and putatively favoured by both restricted microbial transmission
      among related hosts (putatively enhanced by mouthbrooding behavior) and common
      host constraints. This study sets the basis for a future large-scale
      investigation of the gut microbiota of cichlids and its adaptation in the process
      of the host adaptive radiation. 

PMID- 25978453
TI  - Automated glioblastoma segmentation based on a multiparametric structured
      unsupervised classification.
AB  - Automatic brain tumour segmentation has become a key component for the future of
      brain tumour treatment. Currently, most of brain tumour segmentation approaches
      arise from the supervised learning standpoint, which requires a labelled training
      dataset from which to infer the models of the classes. The performance of these
      models is directly determined by the size and quality of the training corpus,
      whose retrieval becomes a tedious and time-consuming task. On the other hand,
      unsupervised approaches avoid these limitations but often do not reach comparable
      results than the supervised methods. In this sense, we propose an automated
      unsupervised method for brain tumour segmentation based on anatomical Magnetic
      Resonance (MR) images. Four unsupervised classification algorithms, grouped by
      their structured or non-structured condition, were evaluated within our pipeline.
      Considering the non-structured algorithms, we evaluated K-means, Fuzzy K-means
      and Gaussian Mixture Model (GMM), whereas as structured classification algorithms
      we evaluated Gaussian Hidden Markov Random Field (GHMRF). An automated
      postprocess based on a statistical approach supported by tissue probability maps
      is proposed to automatically identify the tumour classes after the segmentations.
      We evaluated our brain tumour segmentation method with the public BRAin Tumor
      Segmentation (BRATS) 2013 Test and Leaderboard datasets. Our approach based on
      the GMM model improves the results obtained by most of the supervised methods
      evaluated with the Leaderboard set and reaches the second position in the
      ranking. Our variant based on the GHMRF achieves the first position in the Test
      ranking of the unsupervised approaches and the seventh position in the general
      Test ranking, which confirms the method as a viable alternative for brain tumour
      segmentation. 

PMID- 25978454
TI  - Identification of a 6-cytokine prognostic signature in patients with primary
      glioblastoma harboring M2 microglia/macrophage phenotype relevance.
AB  - BACKGROUND: Glioblastomas (GBM) are comprised of a heterogeneous population of
      tumor cells, immune cells, and extracellular matrix. Interactions among these
      different cell types and pro-/anti-inflammatory cytokines may promote tumor
      development and progression. AIMS: The objective of this study was to develop a
      cytokine-related gene signature to improve outcome prediction for patients with
      primary GBM. METHODS: Here, we used Cox regression and risk-score analysis to
      develop a cytokine-related gene signature in primary GBMs from the whole
      transcriptome sequencing profile of the Chinese Glioma Genome Atlas (CGGA)
      database (n=105). We also examined differences in immune cell phenotype and
      immune factor expression between the high-risk and low-risk groups. RESULTS:
      Cytokine-related genes were ranked based on their ability to predict survival in
      the CGGA database. The six genes showing the strongest predictive value were
      CXCL10, IL17R, CCR2, IL17B, IL10RB, and CCL2. Patients with a high-risk score had
      poor overall survival and progression-free survival. Additionally, the high-risk
      group was characterized by increased mRNA expression of M2 microglia/macrophage
      markers and elevated levels of IL10 and TGFbeta1. CONCLUSION: The six cytokine
      related gene signature is sufficient to predict survival and to identify a
      subgroup of primary GBM exhibiting the M2 cell phenotype.

PMID- 25978455
TI  - Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during
      Transformation.
AB  - Comprehensive analysis of alterations in gene expression along with neoplastic
      transformation in human cells provides valuable information about the molecular
      mechanisms underlying transformation. To further address these questions, we
      performed whole transcriptome analysis to the human mesenchymal stem cell line,
      UE6E7T-3, which was immortalized with hTERT and human papillomavirus type 16
      E6/E7 genes, in association with progress of transformation in these cells. At
      early stages of culture, UE6E7T-3 cells preferentially lost one copy of
      chromosome 13, as previously described; in addition, tumor suppressor genes, DNA
      repair genes, and apoptosis-activating genes were overexpressed. After the loss
      of chromosome 13, additional aneuploidy and genetic alterations that drove
      progressive transformation, were observed. At this stage, the cell line expressed
      oncogenes as well as genes related to anti-apoptotic functions, cell-cycle
      progression, and chromosome instability (CIN); these pro-tumorigenic changes were
      concomitant with a decrease in tumor suppressor gene expression. At later stages
      after prolong culture, the cells exhibited chromosome translocations, acquired
      anchorage-independent growth and tumorigenicity in nude mice, (sarcoma) and
      exhibited increased expression of genes encoding growth factor and DNA repair
      genes, and decreased expression of adhesion genes. In particular, glypican-5
      (GPC5), which encodes a cell-surface proteoglycan that might be a biomarker for
      sarcoma, was expressed at high levels in association with transformation. Patched
      (Ptc1), the cell surface receptor for hedgehog (Hh) signaling, was also
      significantly overexpressed and co-localized with GPC5. Knockdown of GPC5
      expression decreased cell proliferation, suggesting that it plays a key role in
      growth in U3-DT cells (transformants derived from UE6E7T-3 cells) through the Hh
      signaling pathway. Thus, the UE6E7T-3 cell culture model is a useful tool for
      assessing the functional contribution of genes showed by expression profiling to
      the neoplastic transformation of human fibroblasts and human mesenchymal stem
      cells (hMSC). 

PMID- 25978457
TI  - Genome-wide screening of salt tolerant genes by activation-tagging using
      dedifferentiated calli of Arabidopsis and its application to finding gene for Myo
      inositol-1-p-synthase.
AB  - Salinity represents a major abiotic stress factor that can adversely limit the
      production, quality and geographical distribution of crops. In this study we
      focused on dedifferentiated calli with fundamental cell functions, the salt
      tolerance of which had not been previously examined. The experimental approach
      was based on activation tagging without regeneration of plants for the
      identification of salt-tolerant mutants of Arabidopsis. Among 62,000 transformed
      calli that were screened, 18 potential mutants resistant to 150 mM NaCl were
      obtained. Thermal asymmetric interlaced (TAIL)-PCR was performed to determine the
      location of T-DNA integration in the genome. In one line, referred to as salt
      tolerant callus 1 (stc1), expression of a gene [At4g39800: myo-inositol-1-P
      synthase 1 (MIPS1)] was considerably enhanced in calli. Plants regenerated from
      calli showed tolerance to salt in germination and subsequent growth.
      Retransformation of wild-type Arabidopsis with MIPS1 conferred salt tolerance,
      indicating that MIPS1 is the causal gene. The over-expression of MIPS1 increased
      the content of total inositol. The involvement of MIPS1 in salt tolerance through
      the fundamental cell growth has been proved in Arabidopsis. 

PMID- 25978458
TI  - Drug/Dye-Loaded, Multifunctional PEG-Chitosan-Iron Oxide Nanocomposites for
      Methotraxate Synergistically Self-Targeted Cancer Therapy and Dual Model Imaging.
AB  - Multifunctional nanocomposites hold great potential to integrate therapeutic and
      diagnostic functions into a single nanoscale structure. In this paper, we
      prepared the MTX-PEG-CS-IONPs-Cy5.5 nanocomposites by functionalizing the surface
      of chitosan-decorated iron oxide nanoparticles (CS-IONPs) with polyethylene
      glycolated methotraxate (MTX-PEG) and near-infrared fluorescent cyanin dye
      (Cy5.5). A clinically useful PEGylated anticancer prodrug, MTX-PEG, was also
      developed as a tumor cell-specific targeting ligand for self-targeted cancer
      treatment. In such nanocomposites, the advantage was that the orthogonally
      functionalized, self-targeted MTX-PEG-CS-IONPs-Cy5.5 can synergistically combine
      an early phase selective tumor-targeting efficacy with a late-phase cancer
      killing effect, which was also confirmed by dual model (magnetic resonance and
      fluorescence) imaging. Furthermore, with the aids of the folate (FA) receptor
      mediated endocytosis (able to turn cellular uptake "off" in normal cells and "on"
      in cancer cells) and pH/intracellular protease-mediated hydrolyzing peptide bonds
      (able to turn drug release "off" in systemic circulation and "on" inside
      endo/lysosomes), the MTX-PEG-CS-IONPs-Cy5.5 could deliver MTX to FA receptors
      overexpressed cancer cells, showing the improved anticancer activity with the
      reduced side effects. Together, the MTX-PEG-CS-IONPs-Cy5.5 could act as a highly
      convergent, flexible, and simplified system for dual model imaging and
      synergistically self-targeted cancer therapy, holding great promise for versatile
      biomedical applications in future. 

PMID- 25978456
TI  - Development of a learning-oriented computer assisted instruction designed to
      improve skills in the clinical assessment of the nutritional status: a pilot
      evaluation.
AB  - Computer assisted instruction (CAI) is an effective tool for evaluating and
      training students and professionals. In this article we will present a learning
      oriented CAI, which has been developed for students and health professionals to
      acquire and retain new knowledge through the practice. A two-phase pilot
      evaluation was conducted, involving 8 nutrition experts and 30 postgraduate
      students, respectively. In each training session, the software developed guides
      users in the integral evaluation of a patient's nutritional status and helps them
      to implement actions. The program includes into the format clinical tools, which
      can be used to recognize possible patient's needs, to improve the clinical
      reasoning and to develop professional skills. Among them are assessment
      questionnaires and evaluation criteria, cardiovascular risk charts, clinical
      guidelines and photographs of various diseases. This CAI is a complete software
      package easy to use and versatile, aimed at clinical specialists, medical staff,
      scientists, educators and clinical students, which can be used as a learning
      tool. This application constitutes an advanced method for students and health
      professionals to accomplish nutritional assessments combining theoretical and
      empirical issues, which can be implemented in their academic curriculum. 

PMID- 25978459
TI  - Accuracy of i-Scan for Optical Diagnosis of Colonic Polyps: A Meta-Analysis.
AB  - BACKGROUND: i-Scan is a novel virtual chromoendoscopy system designed to enhance
      surface and vascular patterns to improve optical diagnostic performance. Numerous
      prospective studies have been done to evaluate the accuracy of i-Scan in
      differentiating colonic neoplasms from non-neoplasms. i-Scan could be an
      effective endoscopic technique for optical diagnosis of colonic polyps.
      OBJECTIVE: Our aim of this study was to perform a meta-analysis of published data
      to establish the diagnostic accuracy of i-Scan for optical diagnosis of colonic
      polyps. METHODS: We searched PubMed, Medline, Elsevier ScienceDirect and Cochrane
      Library databases. We used a bivariate meta-analysis following a random effects
      model to summarize the data and plotted hierarchical summary receiver-operating
      characteristic (HSROC) curves. The area under the HSROC curve (AUC) serves as an
      indicator of the diagnostic accuracy. RESULTS: The meta-analysis included a total
      of 925 patients and 2312 polyps. For the overall studies, the area under the
      HSROC curve was 0.96. The summary sensitivity was 90.4% (95%CI 85%-94.1%) and
      specificity was 90.9% (95%CI 84.3%-94.9%). In 11 studies predicting polyps
      histology in real-time, the summary sensitivity and specificity was 91.5% (95%CI
      85.7%-95.1%) and 92.1% (95%CI 84.5%-96.1%), respectively, with the AUC of 0.97.
      For three different diagnostic criteria (Kudo, NICE, others), the sensitivity was
      86.3%, 93.0%, 85.0%, respectively and specificity was 84.8%, 94.4%, 91.8%,
      respectively. CONCLUSIONS: Endoscopic diagnosis with i-Scan has accurate optical
      diagnostic performance to differentiate neoplastic from non-neoplastic polyps
      with an area under the HSROC curve exceeding 0.90. Both the sensitivity and
      specificity for diagnosing colonic polyps are over 90%.

PMID- 25978461
TI  - Tunes stuck in your brain: The frequency and affective evaluation of involuntary
      musical imagery correlate with cortical structure.
AB  - Recent years have seen a growing interest in the neuroscience of spontaneous
      cognition. One form of such cognition is involuntary musical imagery (INMI), the
      non-pathological and everyday experience of having music in one's head, in the
      absence of an external stimulus. In this study, aspects of INMI, including
      frequency and affective evaluation, were measured by self-report in 44 subjects
      and related to variation in brain structure in these individuals. Frequency of
      INMI was related to cortical thickness in regions of right frontal and temporal
      cortices as well as the anterior cingulate and left angular gyrus. Affective
      aspects of INMI, namely the extent to which subjects wished to suppress INMI or
      considered them helpful, were related to gray matter volume in right temporopolar
      and parahippocampal cortices respectively. These results provide the first
      evidence that INMI is a common internal experience recruiting brain networks
      involved in perception, emotions, memory and spontaneous thoughts. 

PMID- 25978460
TI  - Microevolution of Virulence-Related Genes in Helicobacter pylori Familial
      Infection.
AB  - Helicobacter pylori, a bacterial pathogen that can infect human stomach causing
      gastritis, ulcers and cancer, is known to have a high degree of genome/epigenome
      diversity as the result of mutation and recombination. The bacteria often infect
      in childhood and persist for the life of the host. One of the reasons of the
      rapid evolution of H. pylori is that it changes its genome drastically for
      adaptation to a new host. To investigate microevolution and adaptation of the H.
      pylori genome, we undertook whole genome sequencing of the same or very similar
      sequence type in multi-locus sequence typing (MLST) with seven genes in members
      of the same family consisting of parents and children in Japan. Detection of
      nucleotide substitutions revealed likely transmission pathways involving
      children. Nonsynonymous (amino acid changing) mutations were found in virulence
      related genes (cag genes, vacA, hcpDX, tnfalpha, ggt, htrA and the collagenase
      gene), outer membrane protein (OMP) genes and other cell surface-related protein
      genes, signal transduction genes and restriction-modification genes. We
      reconstructed various pathways by which H. pylori can adapt to a new human host,
      and our results raised the possibility that the mutational changes in virulence
      related genes have a role in adaptation to a child host. Changes in restriction
      modification genes might remodel the methylome and transcriptome to help
      adaptation. This study has provided insights into H. pylori transmission and
      virulence and has implications for basic research as well as clinical practice. 

PMID- 25978462
TI  - Occipital long-interval paired pulse TMS leads to slow wave components in NREM
      sleep.
AB  - Neural correlates of conscious vs unconscious states can be studied by
      contrasting EEG markers of brain activity between those two states. Here, a task
      free experimental setup was used to study the state dependent effects of
      occipital transcranial magnetic stimulation (TMS). EEG responses to single and
      paired pulse TMS with an inter-stimulus-interval (ISI) of 100 ms were
      investigated under Non-REM (NREM) sleep and wakefulness. In the paired pulse TMS
      condition adopting this long ISI, a robust positive deflection starting around
      200 ms after the second pulse was found. This component was not obtained under
      wakefulness or when a single TMS pulse was applied in sleep. These findings are
      discussed in the context of NREM sleep slow waves. The present results indicate
      that the long interval paired-pulse paradigm could be used to manipulate
      plasticity processes in the visual cortex. The present setup might also become
      useful for evaluating states of consciousness.

PMID- 25978464
TI  - Serotonin depletion-induced maladaptive aggression requires the presence of
      androgens.
AB  - The sex hormone testosterone and the neurotransmitter serotonin exert opposite
      effects on several aspects of behavior including territorial aggression. It is
      however not settled if testosterone exerts its pro-aggressive effects by reducing
      serotonin transmission and/or if the anti-aggressive effect of serotonin requires
      the presence of the androgen. Using the resident intruder test, we now show that
      administration of the serotonin synthesis inhibitor para-chlorophenylalanine (300
      mg/kg x 3 days) increases the total time of attack as well as the percentage
      amount of social behavior spent on attack but not that spent on threat - i.e.
      that it induces a pattern of unrestricted, maladaptive aggression - in
      gonadectomized C57Bl/6 male mice receiving testosterone replacement; in contrast,
      it failed to reinstate aggression in those not given testosterone. Whereas these
      results suggest the pro-aggressive effect of testosterone to be independent of
      serotonin, and not caused by an inhibition of serotonergic activity, the pCPA
      induced induction of maladaptive aggression appears to require the presence of
      the hormone. In line with these findings, pCPA enhanced the total time of attack
      as well the relative time spent on attacks but not threats also in wild-type
      gonadally intact male C57Bl/6 mice, but failed to reinstate aggression in mice
      rendered hypo-aggressive by early knock-out of androgen receptors in the brain
      (ARNesDel mice). We conclude that androgenic deficiency does not dampen
      aggression by unleashing an anti-aggressive serotonergic influence; instead
      serotonin seems to modulate aggressive behavior by exerting a parallel-coupled
      inhibitory role on androgen-driven aggression, which is irrelevant in the absence
      of the hormone, and the arresting of which leads to enhanced maladaptive
      aggression. 

PMID- 25978463
TI  - The Intraperitoneal Transcriptome of the Opportunistic Pathogen Enterococcus
      faecalis in Mice.
AB  - Enterococcus faecalis is a Gram-positive lactic acid intestinal opportunistic
      bacterium with virulence potential. For a better understanding of the adapation
      of this bacterium to the host conditions, we performed a transcriptome analysis
      of bacteria isolated from an infection site (mouse peritonitis) by RNA
      sequencing. We identified a total of 211 genes with significantly higher
      transcript levels and 157 repressed genes. Our in vivo gene expression database
      reflects well the infection process since genes encoding important virulence
      factors like cytolysin, gelatinase or aggregation substance as well as stress
      response proteins, are significantly induced. Genes encoding metabolic activities
      are the second most abundant in vivo induced genes demonstrating that the
      bacteria are metabolically active and adapt to the special nutrient conditions of
      the host. alpha- and beta- glucosides seem to be important substrates for E.
      faecalis inside the host. Compared to laboratory conditions, the flux through the
      upper part of glycolysis seems to be reduced and more carbon may enter the
      pentose phosphate pathway. This may reflect the need of the bacteria under
      infection conditions to produce more reducing power for biosynthesis. Another
      important substrate is certainly glycerol since both pathways of glycerol
      catabolism are strongly induced. Strongly in vivo induced genes should be
      important for the infection process. This assumption has been verified in a
      virulence test using well characterized mutants affected in glycerol metabolism.
      This showed indeed that mutants unable to metabolize this sugar alcohol are
      affected in organ colonisation in a mouse model. 

PMID- 25978465
TI  - "The one who chases you away does not tell you go": silent refusals and complex
      power relations in research consent processes in Coastal Kenya.
AB  - Consent processes have attracted significant research attention over the last
      decade, including in the global south. Although relevant studies suggest consent
      is a complex negotiated process involving multiple actors, most guidelines assume
      consent is a one-off encounter with a clear 'yes' or 'no' decision. In this paper
      we explore the concept of 'silent refusals', a situation where it is not clear
      whether potential participants want to join studies or those in studies want to
      withdraw from research, as they were not actively saying no. We draw on
      participant observation, in-depth interviews and group discussions conducted with
      a range of stakeholders in two large community based studies conducted by the
      KEMRI Wellcome Trust programme in coastal Kenya. We identified three broad inter
      related rationales for silent refusals: 1) a strategy to avoid conflicts and
      safeguard relations within households, - for young women in particular-to appear
      to conform to the wishes of elders; 2) an approach to maintain friendly,
      appreciative and reciprocal relationships with fieldworkers, and the broader
      research programme; and 3) an effort to retain study benefits, either for
      individuals, whole households or wider communities. That refusals and underlying
      rationales were silent posed multiple dilemmas for fieldworkers, who are
      increasingly recognised to play a key interface role between researchers and
      communities in many settings. Silent refusals reflect and reinforce complex power
      relations embedded in decisions about research participation, with important
      implications for consent processes and broader research ethics practice.
      Fieldworkers need support to reflect upon and respond to the ethically charged
      environment they work in. 

PMID- 25978466
TI  - Classification of Tree Species in Overstorey Canopy of Subtropical Forest Using
      QuickBird Images.
AB  - This paper proposes a supervised classification scheme to identify 40 tree
      species (2 coniferous, 38 broadleaf) belonging to 22 families and 36 genera in
      high spatial resolution QuickBird multispectral images (HMS). Overall kappa
      coefficient (OKC) and species conditional kappa coefficients (SCKC) were used to
      evaluate classification performance in training samples and estimate accuracy and
      uncertainty in test samples. Baseline classification performance using HMS images
      and vegetation index (VI) images were evaluated with an OKC value of 0.58 and
      0.48 respectively, but performance improved significantly (up to 0.99) when used
      in combination with an HMS spectral-spatial texture image (SpecTex). One of the
      40 species had very high conditional kappa coefficient performance (SCKC >= 0.95)
      using 4-band HMS and 5-band VIs images, but, only five species had lower
      performance (0.68 <= SCKC <= 0.94) using the SpecTex images. When SpecTex images
      were combined with a Visible Atmospherically Resistant Index (VARI), there was a
      significant improvement in performance in the training samples. The same level of
      improvement could not be replicated in the test samples indicating that a high
      degree of uncertainty exists in species classification accuracy which may be due
      to individual tree crown density, leaf greenness (inter-canopy gaps), and noise
      in the background environment (intra-canopy gaps). These factors increase
      uncertainty in the spectral texture features and therefore represent potential
      problems when using pixel-based classification techniques for multi-species
      classification. 

PMID- 25978467
TI  - Anaesthetic or lubricating gels for urethral catheterisation?

PMID- 25978468
TI  - Held tight: choosing the right catheter-securement device.

PMID- 25978469
TI  - Reducing inappropriate urinary catheter use: quality care initiatives.
AB  - Healthcare-acquired urinary infection presents a substantial burden for patients
      and the healthcare system. Urinary tract infections have not gained the same
      level of media attention as other healthcare-associated infections, yet
      interventions to reduce urinary catheter use are one of the top ten recommended
      patient safety strategies. To improve practice around urinary catheter placement
      and removal requires interventions to change the expectations and habits of
      nurses, medical teams and patients regarding the need for a urinary catheter. In
      the authors' trust, a redesign of the existing urinary catheter device record was
      undertaken to help avoid unnecessary placement of catheters, and resulted in a
      reduction of urinary catheters in situ longer than 48 hours. Other strategies
      included implementation of catheter rounds in a high-usage area, and credit-card
      sized education cards. A catheter 'passport' was introduced for patients
      discharged with a catheter to ensure information for insertion and ongoing use
      were effectively communicated. 

PMID- 25978471
TI  - Workforce survey: prostate cancer care.

PMID- 25978470
TI  - Prostatectomy: information provision and education for patients.
AB  - Following the diagnosis of prostate cancer, information should be imparted to
      ensure an informed decision regarding treatment can be made. The impact of a
      cancer diagnosis could lead men to opt for surgical intervention without fully
      understanding the consequences of treatment. Effective communication of evidence
      based information can assist men to fully understand the consequences of
      treatment. Radical prostatectomy, whether robotically assisted laparoscopic or
      retropubic, will lead to quality-of-life issues with functional outcomes such as
      erectile dysfunction and urinary incontinence being at the forefront. Issues
      should be discussed and communicated in depth so that frustration and regret
      following treatment are avoided. A cautious approach to information provision
      should be considered so the patient does not feel in a position of information
      overload. Advanced communication skills are of utmost importance to ensure
      information is tailored to suit individual needs, as no one model of information
      giving suits all. This article is a rapid literature search relating to post
      prostatectomy functional outcomes and how communication and information giving
      before treatment assists with acceptance of treatment outcomes. 

PMID- 25978472
TI  - The male experience of ISC with a silicone catheter.
AB  - Since its introduction in the 1970s, intermittent self-catheterisation (ISC) has
      become more common and should be considered the method of choice for draining
      retained urine. The realisation for male patients that they require
      catheterisation can be associated with a significant physical and psychological
      burden (Shaw and Logan, 2013). This article describes a UK multi-centre patient
      satisfaction survey evaluating the features of a male ISC silicone catheter. The
      survey was aimed at determining patient preferences and perceptions of learning
      ISC with the intermittent catheter to evaluate if a silicone catheter is
      acceptable and user friendly. This information is intended to be used to expand
      the knowledge base around catheter selection and help guide nurses who offer a
      choice of catheters when teaching ISC to patients.

PMID- 25978473
TI  - Uro-oncology consultant nurse.

PMID- 25978474
TI  - Incontinence-associated dermatitis: identification, prevention and care.
AB  - Incontinence-associated dermatitis (IAD) is a common skin disorder experienced by
      people who suffer from faecal and/or urinary incontinence. It is painful and in
      some cases accompanied by significant secondary infections. The prevalence is
      higher in those people receiving long-term care at home. IAD is often
      misdiagnosed and confused with pressure ulcers. Care providers now crossover
      health and social care boundaries and education on continence-related issues is
      often not prioritised. This article looks at normal skin physiology and the
      aetiology of IAD versus pressure ulcers. It suggests prevention and management
      strategies in relation to IAD; in particular, the use of barrier creams. A
      selection of case studies evaluating the efficacy of using Cutimed PROTECT cream
      in cases of IAD are presented. 

PMID- 25978475
TI  - Cardboard versus sterile containers: more nitrite-positive urinalysis results?
AB  - Urinalysis is a frequently performed test that provides valuable information as
      to the health of individuals. The presence of nitrites in the urine may indicate
      infection. Antibiotic therapy is commonly started following the results of
      dipstick urine taken from non-sterile urine samples. This is especially prevalent
      in men who are immobile, because sterile containers large enough to hold a full
      bladder of urine are not available (at the author's trust). Urine samples were
      taken from 25 male A&E patients in a sterile container. Half of each sample was
      decanted into an ordinary cardboard urine bottle and both samples were then
      tested using dipstick urinalysis after 1 minute and after 10 minutes to see if
      there was a difference in the presence of nitrites between the two container
      types. After 10 minutes, 21 of the 25 samples showed a positive nitrite dipstick
      in the cardboard container while it remained negative when the urine remained in
      the sterile container. These results demonstrate that care needs to be taken when
      collecting urine samples, and the results of dipstick urinalysis should be used
      with caution depending on the collection method. 

PMID- 25978476
TI  - Global Epidemiology of HIV Among Women and Girls Who Use or Inject Drugs: Current
      Knowledge and Limitations of Existing Data.
AB  - BACKGROUND: Women and girls who use and inject drugs are a critical population at
      risk of HIV. In this article, we review data on the epidemiology of drug use and
      injection among women globally and HIV prevalence among women and girls who use
      and inject drugs. RESULTS: Women and girls comprise one-third of people who use
      and inject drugs globally. There is substantial variation in HIV prevalence in
      this population, between and within countries. There is a pronounced lack of data
      examining HIV risk among particularly vulnerable subpopulations of women who use
      and inject drugs, including women who have sex with women, transgender women,
      racial and ethnic minority women, and young women. Women who use and inject drugs
      experience stigma and discrimination that affect access to services, and high
      levels of sexual risk exposures. CONCLUSIONS: There are significant gaps in our
      understanding of the epidemiology of drug use and injecting among women and girls
      and HIV risk and prevalence in this population. Women are frequently
      underrepresented in studies of drug use and HIV risk and prevalence among people
      who inject drugs, limiting our understanding of possible sex differences in this
      population. Most research originates from developed countries and may not be
      generalizable to other settings. A great deal of work is needed to improve
      understanding of HIV among particularly vulnerable subpopulations, such as
      transgender women who use drugs. Better data are critical to efforts to advocate
      for the needs of women and girls who use and inject drugs.

PMID- 25978477
TI  - Substance Use and HIV Among Female Sex Workers and Female Prisoners: Risk
      Environments and Implications for Prevention, Treatment, and Policies.
AB  - Female sex workers (FSWs) and female prisoners experience elevated HIV prevalence
      relative to the general population because of unprotected sex and unsafe drug use
      practices, but the antecedents of these behaviors are often structural in nature.
      We review the literature on HIV risk environments for FSWs and female prisoners,
      highlighting similarities and differences in the physical, social, economic, and
      policy/legal environments that need to be understood to optimize HIV prevention,
      treatment, and policy responses. Sex work venues, mobility, gender norms, stigma,
      debt, and the laws and policies governing sex work are important influences in
      the HIV risk environment among FSWs, affecting their exposure to violence and
      ability to practice safer sex and safer drug use behaviors. Female prisoners are
      much more likely to have a drug problem than do male prisoners and have higher
      HIV prevalence, yet are much less likely to have access to HIV prevention and
      treatment and access to drug treatment in prison. Women who trade sex or are
      imprisoned and engage in substance use should not be considered in separate silos
      because sex workers have high rates of incarceration and many female prisoners
      have a history of sex work. Repeated cycles of arrest, incarceration, and release
      can be socially and economically destabilizing for women, exacerbating their HIV
      risk. This dynamic interplay requires a multisectoral approach to HIV prevention
      and treatment that appreciates and respects that not all women are willing, able,
      or want to stop sex work or drug use. Women who engage in sex work, use drugs, or
      are imprisoned come from all communities and deserve sustained access to HIV
      prevention and treatment for substance use and HIV, helping them and their
      families to lead healthy and satisfying lives. 

PMID- 25978478
TI  - Targeting the SAVA (Substance Abuse, Violence, and AIDS) Syndemic Among Women and
      Girls: A Global Review of Epidemiology and Integrated Interventions.
AB  - OBJECTIVES: Multiple pathways link gender-based violence (GBV) to HIV and other
      sexually transmitted infections among women and girls who use or inject drugs.
      The aim of this article is to synthesize global literature that examines
      associations among the synergistic epidemics of substance abuse, violence, and
      HIV/AIDS, known as the SAVA syndemic. It also aims to identify a continuum of
      multilevel integrated interventions that target key SAVA syndemic mechanisms.
      METHODS: We conducted a selective search strategy, prioritizing use of meta
      analytic epidemiological and intervention studies that address different aspects
      of the SAVA syndemic among women and girls who use drugs worldwide from 2000 to
      2015 using PubMed, MEDLINE, and Google Scholar. RESULTS: Robust evidence from
      different countries suggests that GBV significantly increases the risk of HIV and
      other sexually transmitted infections among women and girls who use drugs.
      Multiple structural, biological, and behavioral mechanisms link GBV and HIV among
      women and girls. Emerging research has identified a continuum of brief and
      extended multilevel GBV prevention and treatment interventions that may be
      integrated into a continuum of HIV prevention, testing, and treatment
      interventions to target key SAVA syndemic mechanisms among women and girls who
      use drugs. CONCLUSIONS: There remain significant methodological and geographical
      gaps in epidemiological and intervention research on the SAVA syndemic,
      particularly in low- and middle-income countries. This global review underscores
      the need to advance a continuum of multilevel integrated interventions that
      target salient mechanisms of the SAVA syndemic, especially for adolescent girls,
      young women, and transgender women who use drugs.

PMID- 25978479
TI  - Gender-Specific HIV Prevention Interventions for Women Who Use Alcohol and Other
      Drugs: The Evolution of the Science and Future Directions.
AB  - The use of alcohol and other drugs (AODs) is an important driver of gender
      disparities in HIV prevalence. Consequently, there is a need for women-specific
      HIV interventions that are conceptualized to address (1) women's risk behavior,
      their roles in sexual relationships, and gender power dynamics and (2) other
      issues commonly faced by women who use AODs, such as gender-based violence and
      victimization. This article presents the evolution of HIV prevention intervention
      research with women who use AODs. It looks at 3 generations of women-focused HIV
      research interventions, including first-generation projects that started in the
      1990s, second-generation efforts where projects expanded in scope and included
      adaptions of evidence-based interventions for global relevance, and finally third
      generation projects currently underway that combine biobehavioral methods and are
      being implemented in real-world settings. Because women who use AODs continue to
      report risk behaviors related to HIV, emphasis should be placed on training
      scientists to conduct gender-specific studies, increasing funding for new
      studies, and advocating to ensure that stigma-free services are available for
      these at-risk women. 

PMID- 25978480
TI  - Structural Interventions for HIV Prevention Among Women Who Use Drugs: A Global
      Perspective.
AB  - We briefly review extant literature on the contextual sources of HIV risk among
      drug users-the drug user risk environment-and on structural interventions to
      address drug user vulnerability to HIV. We argue that issues of gender inequality
      and gendered power relations are largely absent from this literature. We then
      identify 5 contextual factors that are critical for understanding women's HIV
      related vulnerability and whose impacts are exacerbated among women who use
      drugs, including a division of reproductive labor in which women bear primary
      responsibility for family caretaking, women's lack of full access to or control
      of productive resources and decision making, women's vulnerability to sexual and
      physical violence, and especially, intimate partner violence, women's
      (particularly heterosexual women's) relationship dependency and limited power in
      sexual interactions, and harmful gender norms that reinforce these other factors.
      We discuss a range of structural interventions and structural intervention
      approaches with the potential to address these contextual factors and call for
      more research, both to better understand the risk environment of women who use
      drugs and the impacts of structural interventions on it. We argue that our
      understanding of and ability to impact on the HIV-related risk environment of
      drug users is incomplete if we do not fully incorporate the analysis of gender
      inequality and gendered power relations.

PMID- 25978481
TI  - Theoretical Foundations of Research Focused on HIV Prevention Among Substance
      Involved Women: A Review of Observational and Intervention Studies.
AB  - Although substance use continues to be a significant component of HIV risk among
      women worldwide, to date, relatively little attention has been paid in research,
      services, or policy to substance-involved women (SIW). HIV acquisition for SIW
      stems from transmission risks directly related to substance use and risks
      associated with sexual activity in which power to negotiate risk and safety are
      influenced by dynamics of male partnerships, sex work, and criminalization (of
      both drug use and sex work), among other factors. As such, HIV risk for SIW
      resides as much in the environment-physical, social, cultural, economic, and
      political-in which drug use occurs as it does from transmission-related behaviors
      of individual women. To reduce HIV infections among SIW, it is important to
      specify the interaction of individual- and environmental-level factors,
      including, but not limited to those related to women's own substance use, that
      can and ought to be changed. This involves theorizing about the interplay of
      gender, substance use, and HIV risk, and incorporating that theoretical
      understanding into intervention design and evaluation. A review of the published
      literature focused on HIV prevention among SIW revealed a general lack of
      theoretical and conceptual foundation specific to the gender-related and
      environmental drivers of HIV in this population. Greater theoretical linkages to
      intersectionality and syndemic approaches are recommended to better identify and
      target relevant mechanisms by which the interplay of gender dynamics and
      substance use potentiate the likelihood of HIV acquisition and transmission among
      SIW.

PMID- 25978482
TI  - Drug Treatment as HIV Prevention Among Women and Girls Who Inject Drugs From a
      Global Perspective: Progress, Gaps, and Future Directions.
AB  - Although there have been significant reductions in the number of new HIV
      infections globally from 2009 to 2013, incidence remains unacceptably high for
      persons who use drugs. In many settings, women and girls who inject drugs (WWID)
      with HIV/AIDS experience poor treatment access, including evidence-based
      practices like antiretroviral therapy and drug treatment. Medication-assisted
      therapies (MAT) for substance use disorders are especially inaccessible, which in
      their absence, increases HIV transmission risk. Irrespective of setting or
      culture, drug treatment using MAT is not only effective but also cost-effective
      at reducing opioid use and linked injection and sexual risks. Data presented here
      for WWID address their access to MAT for opioid addiction and to treatments being
      developed that address the relationship, family, and vocational needs of this
      group. The most glaring finding is that globally, WWID frequently are excluded in
      surveys or studies with an impressive lack of disaggregated data by gender when
      surveying access to MAT-even in wealthy countries. Despite this, there have been
      some striking improvements in implementing drug treatment as prevention, notably
      in Iran and China. Still, real barriers remain for women and girls to accessing
      drug treatment, other harm reduction services, and antiretroviral therapy.
      Development and/or implementation of interventions that facilitate women and
      girls engaging in drug treatment that address their roles within society, work,
      and family/relationships, and outcome evaluation of these interventions are
      crucial.

PMID- 25978483
TI  - HIV Testing, Care, and Treatment Among Women Who Use Drugs From a Global
      Perspective: Progress and Challenges.
AB  - The article reviews data on HIV testing, treatment, and care outcomes for women
      who use drugs in 5 countries across 5 continents. We chose countries in which the
      HIV epidemic has, either currently or historically, been fueled by injection and
      non-injection drug use and that have considerable variation in social structural
      and drug policies: Argentina, Vietnam, Australia, Ukraine, and the United States.
      There is a dearth of available HIV care continuum outcome data [ie, testing,
      linkage, retention, antiretroviral therapy (ART) provision, viral suppression]
      among women drug users, particularly among noninjectors. Although some progress
      has been made in increasing HIV testing in this population, HIV-positive women
      drug users in 4 of the 5 countries have not fully benefitted from ART nor are
      they regularly engaged in HIV care. Issues such as the criminalization of drug
      users, HIV-specific criminal laws, and the lack of integration between substance
      use treatment and HIV primary care play a major role. Strategies that effectively
      address the pervasive factors that prevent women drug users from engaging in HIV
      care and benefitting from ART and other prevention services are critical. Future
      success in enhancing the HIV continuum for women drug users should consider
      structural and contextual level barriers and promote social, economic, and legal
      policies that overhaul the many years of discrimination and stigmatization faced
      by women drug users worldwide. Such efforts must emphasis the translation of
      policies into practice and approaches to implementation that can help HIV
      infected women who use drugs engage at all points of the HIV care continuum. 

PMID- 25978484
TI  - Biomedical HIV Prevention Including Pre-exposure Prophylaxis and Opiate Agonist
      Therapy for Women Who Inject Drugs: State of Research and Future Directions.
AB  - Women who inject drugs (WWID) are at higher risk of HIV compared with their male
      counterparts as a result of multiple factors, including biological, behavioral,
      and sociostructural factors, yet comparatively little effort has been invested in
      testing and delivering prevention methods that directly target this group. In
      this article, we discuss the need for expanded prevention interventions for WWID,
      focusing on 2 safe, effective, and approved, yet underutilized biomedical
      prevention methods: opiate agonist therapy (OAT) and oral pre-exposure
      prophylaxis (PrEP). Although both interventions are well researched, they have
      not been well examined in the context of gender. We discuss the drivers of women
      injectors' higher HIV risk, review the effectiveness of OAT and PrEP
      interventions among women, and explain why these new HIV prevention tools should
      be prioritized for WWID. There is substantial potential for impact of OAT and
      PrEP programs for WWID in the context of broader gender-responsive HIV prevention
      initiatives. Although awaiting efficacy data on other biomedical approaches in
      the HIV prevention research "pipeline," we propose that the scale-up and
      implementation of these proven, safe, and effective interventions are needed now.

PMID- 25978485
TI  - HIV, HCV, and Health-Related Harms Among Women Who Inject Drugs: Implications for
      Prevention and Treatment.
AB  - BACKGROUND: Although an estimated 3.5 million women inject drugs globally, women
      are outnumbered 4 to one by men who inject drugs and are often ignored or
      overlooked in the development and delivery of prevention and treatment services
      for this population. This study aimed to identify key comorbidities prevalent
      among women who inject drugs (WWID), consider factors that contribute to
      vulnerability of this population, and examine implications for prevention and
      treatment. METHODS: The literature was reviewed to examine the specific
      challenges and needs of WWID. We searched health-related bibliographic databases
      and grey literature to identify studies conducted among WWID and studies
      conducted among people who inject drugs (PWID), where results were disaggregated
      by gender and policies/guidelines/reports relevant to WWID. RESULTS: WWID face a
      range of unique, gender-specific, and often additional challenges and barriers.
      The lack of a targeted focus on WWID by prevention and treatment services and
      harm-reduction programs increases women's vulnerability to a range of health
      related harms, including blood-borne viral and sexually transmitted infections,
      injection-related injuries, mental health issues, physical and sexual violence,
      poor sexual and reproductive health, issues in relation to childbearing and child
      care, and pervasive stigma and discrimination. CONCLUSIONS: There is a need to
      improve the collection and reporting of gender-disaggregated data on prevalence
      of key infections and prevention and treatment service access and program
      coverage. Women-focussed services and integrating gender equity and human rights
      into the harm-reduction programming will be a prerequisite if improvements in the
      health, safety, and well-being of this often invisible and highly vulnerable
      population are to be achieved.

PMID- 25978487
TI  - Complex interaction of gender-specific factors and substance use among women.
      Preface.

PMID- 25978486
TI  - Women Who Use or Inject Drugs: An Action Agenda for Women-Specific, Multilevel,
      and Combination HIV Prevention and Research.
AB  - Women account for more than half of all individuals living with HIV globally.
      Despite increasing drug and HIV epidemics among women, women who use drugs are
      rarely found in research, harm reduction programs, or drug and HIV treatment and
      care. Women who use drugs continue to face challenges that increase their
      vulnerability to HIV and other comorbidities because of high rates of gender
      based violence, human rights violations, incarceration, and institutional and
      societal stigmatization. This special issue emphasizes how the burdens of HIV,
      drug use, and their co-occurring epidemics affect women in a global context.
      Articles included focus on the epidemiologies of HIV and hepatitis C virus and
      other comorbidities; HIV treatment, prevention, and care; and policies affecting
      the lives of women who use drugs. This issue also highlights the state of the
      science of biomedical and behavioral research related to women who use drugs. The
      final article highlights the major findings of articles covered and presents a
      call to action regarding needed research, treatment, and preventive services for
      women who use drugs. To address these needs, we advocate for women-specific
      thinking and approaches that consider the social, micro, and macro contexts of
      women's lives. We present a women-specific risk environment framework that
      reflects the unique lives and contexts of women who use drugs and provides a call
      to action for intervention, prevention, and policies. 

PMID- 25978488
TI  - Bringing Female Substance Users to the Center of the Global HIV Response.

PMID- 25978489
TI  - What interventions are needed for women and girls who use drugs? A global
      perspective.
AB  - Women and girls who inject drugs are more likely than their male counterparts to
      acquire HIV. In addition to criminalization, punitive laws, and social stigma
      that puts all injecting drug users at increased risk, women are made even more
      vulnerable by social, economic, and culturally embedded power imbalances. Women
      and girls are also less likely to seek treatment and healthcare, even when they
      are pregnant. This is in part due to underfunded harm reduction and drug
      treatment programs limited in their ability to surmount the unique barriers women
      face. This does not have to be the reality. There are steps-some simple, some
      more complex-that can reduce infection rates and provide women and girls with
      health care and harm reduction services that are designed with their needs and
      concerns in mind. 

PMID- 25978490
TI  - HIV Reduction Among Women Who Inject Drugs Can Be Achieved Through Women-Specific
      Programs and Global Targets: A Model From Ukraine.

PMID- 25978491
TI  - Fabrication of a novel graphene oxide/beta-FeOOH composite and its adsorption
      behavior for copper ions from aqueous solution.
AB  - A graphene oxide (GO)/beta-FeOOH composite was prepared by the liquid insert
      method and was characterized by XRD, FT-IR, SEM and TEM. The adsorption capacity
      of the composite was evaluated by the removal of copper ions (Cu(2+)) from
      aqueous solution. The effect of initial pH, contact time and absorbent dose on
      the removal efficiency of Cu(2+) was investigated by batch experiments. Langmuir
      and Freundlich models were employed to describe the adsorption equilibrium. The
      adsorption kinetics was investigated by both the pseudo-first-order and pseudo
      second-order kinetics models. The results showed that the GO/beta-FeOOH composite
      exhibited excellent adsorption capacity for Cu(2+) and under the optimum
      experimental conditions, the removal rate of Cu(2+) can reach ca. 93.8%. The
      adsorption isotherm was a good fit with the Langmuir model and the adsorption
      process was described by the pseudo-second-order kinetics model. 

PMID- 25978493
TI  - Markerless human motion tracking using hierarchical multi-swarm cooperative
      particle swarm optimization.
AB  - The high-dimensional search space involved in markerless full-body articulated
      human motion tracking from multiple-views video sequences has led to a number of
      solutions based on metaheuristics, the most recent form of which is Particle
      Swarm Optimization (PSO). However, the classical PSO suffers from premature
      convergence and it is trapped easily into local optima, significantly affecting
      the tracking accuracy. To overcome these drawbacks, we have developed a method
      for the problem based on Hierarchical Multi-Swarm Cooperative Particle Swarm
      Optimization (H-MCPSO). The tracking problem is formulated as a non-linear 34
      dimensional function optimization problem where the fitness function quantifies
      the difference between the observed image and a projection of the model
      configuration. Both the silhouette and edge likelihoods are used in the fitness
      function. Experiments using Brown and HumanEva-II dataset demonstrated that H
      MCPSO performance is better than two leading alternative approaches-Annealed
      Particle Filter (APF) and Hierarchical Particle Swarm Optimization (HPSO).
      Further, the proposed tracking method is capable of automatic initialization and
      self-recovery from temporary tracking failures. Comprehensive experimental
      results are presented to support the claims. 

PMID- 25978492
TI  - Affective resonance in response to others' emotional faces varies with affective
      ratings and psychopathic traits in amygdala and anterior insula.
AB  - Despite extensive research on the neural basis of empathic responses for pain and
      disgust, there is limited data about the brain regions that underpin affective
      response to other people's emotional facial expressions. Here, we addressed this
      question using event-related functional magnetic resonance imaging to assess
      neural responses to emotional faces, combined with online ratings of subjective
      state. When instructed to rate their own affective response to others' faces,
      participants recruited anterior insula, dorsal anterior cingulate, inferior
      frontal gyrus, and amygdala, regions consistently implicated in studies
      investigating empathy for disgust and pain, as well as emotional saliency.
      Importantly, responses in anterior insula and amygdala were modulated by trial-by
      trial variations in subjective affective responses to the emotional facial
      stimuli. Furthermore, overall task-elicited activations in these regions were
      negatively associated with psychopathic personality traits, which are
      characterized by low affective empathy. Our findings suggest that anterior insula
      and amygdala play important roles in the generation of affective internal states
      in response to others' emotional cues and that attenuated function in these
      regions may underlie reduced empathy in individuals with high levels of
      psychopathic traits. 

PMID- 25978494
TI  - Identification of human basic fetoprotein as glucose-6-phosphate isomerase by
      using N- and C-terminal sequence tags and terminal tag database.
AB  - Human basic fetoprotein (BFP), found in fetal serum and tissue extracts as well
      as in extracts of various cancer tissues, has long been known as a marker protein
      for cancers; however, the primary sequence has not yet been reported. This paper
      describes the identification of BFP using the N- and C-terminal amino acid
      sequence tags (Ac-AALTRDPQFQ and QQREARVQ, respectively) clarified by mass
      spectrometry-based methods, and a terminal tag database (ProteinCarta). In this
      study, BFP was identified as glucose-6-phosphate isomerase (G6PI_HUMAN). 

PMID- 25978495
TI  - Solid phase extraction in tandem with GC/MS for the determination of semi
      volatile organic substances extracted from pharmaceutical packaging/delivery
      systems via aqueous solvent systems.
AB  - An extractable survey is one of several studies performed on a pharmaceutical
      storage/delivery system as part of the process of demonstrating that the system
      is suitable for its intended use. In this paper, a solid phase extraction method
      for the preparation of aqueous extracts generated during an extractable survey is
      presented. The method offers a convenient means to isolate semi-volatile organic
      extractable compounds from aqueous extraction solvents for analysis by gas
      chromatography/mass spectrometry. Following the solid phase extraction procedure,
      derivatization is performed to convert problematic functionalities (such as
      amines and acids) into appropriate chromatographically friendly derivatives.
      Demonstration of method performance is achieved in three ways using a set of 31
      commonly observed extractable substances as model compounds. First, a
      breakthrough experiment was performed with a 2 solvent system consisting of water
      and 10/90 isopropanol/water over a range of 6 mL to 100 mL. Results from this
      experiment show only caprolactam possessed a significant level of breakthrough in
      either solvent over the range of volumes evaluated. Second, a formal
      accuracy/precision study was conducted using a three solvent system consisting of
      water, 10/90 isopropanol/water and 1% polysorbate 80. This experiment
      demonstrates the quantitative ability of the method at levels ranging from 20
      ng/mL to 50 MUg/mL. Recovery values of 70% to 130% of the theoretical
      concentration, with relative standard deviation values of less than 15% for
      replicate preparations, are obtained for a majority of the compounds evaluated.
      Finally, a case study involving the extraction of an intravenous drug delivery
      bag with multiple aqueous solvent systems further demonstrates the viability of
      solid phase extraction for use in an extractables survey.

PMID- 25978496
TI  - A sensitive biosensor with a DNAzyme for lead(II) detection based on fluorescence
      turn-on.
AB  - In this paper, we described a new DNAzyme-based fluorescent biosensor for the
      detection of Pb(2+). In the biosensor, the bulged structure is formed between the
      substrate labeled with fluorescein amidite (FAM) and DNAzyme after being
      annealed. Ethidium bromide (EB), the DNA intercalator, then intercalates into the
      double-stranded DNA section. Once FAM is excited, the FRET takes place from FAM
      to EB, which leads to the fluorescence of FAM decreasing greatly. In the presence
      of Pb(2+), the substrate is cleaved by DNAzyme, which breaks the bulged
      structure. Then EB is released and the FRET from FAM to EB is inhibited. In this
      case, the fluorescence of FAM increases dramatically. Thus, the Pb(2+) ions can
      be detected by measuring the fluorescence enhancement of FAM. Under optimal
      conditions, the increased fluorescence intensity ratio of FAM is dependent on the
      lead level in the sample, and exhibits a linear response over a Pb(2+)
      concentration range of 0-100 nM with a detection limit of 530 pM. The sensor
      showed high selectivity in the presence of a number of interference ions. The
      river water samples were also tested with satisfying results by using the new
      method. This sensor is highly sensitive and simple without any additional
      treatments, which provides a platform for other biosensors based on DNAzyme. 

PMID- 25978497
TI  - Structure and Dynamics of Phospholipid Nanodiscs from All-Atom and Coarse-Grained
      Simulations.
AB  - We investigated structural and dynamical properties of nanodiscs comprising
      dimyristoylphosphatidylcholine (DMPC) lipids and major scaffold protein
      MSP1Delta(1-22) from human apolipoprotein A-1 using combined all-atom and coarse
      grained (CG) molecular dynamics (MD) simulations. The computational efficiency of
      the Martini-CG force field enables the spontaneous self-assembly of lipids and
      scaffold proteins into stable nanodisc structures on time scales up to tens of
      microseconds. Subsequent all-atom and CG-MD simulations reveal that the lipids in
      the nanodisc have lower configurational entropy and higher acyl tail order than
      in a lamellar bilayer phase. These altered average properties arise from rather
      differential behavior of lipids, depending on their location in the nanodisc.
      Since the scaffold proteins exert constrictive forces from the outer rim of the
      disc toward its center, lipids at the center of the nanodisc are highly ordered,
      whereas annular lipids that are in contact with the MSP proteins are remarkably
      disordered due to perturbed packing. Although specific differences between all
      atom and CG simulations are also evident, the results obtained at both levels of
      resolution are in overall good agreement with each other and provide atomic level
      interpretations of recent experiments. Thus, the present study highlights the
      applicability of multiscale simulation approaches for nanodisc systems and opens
      the way for future applications, including the study of nanodisc-embedded
      membrane proteins. 

PMID- 25978498
TI  - Methionine synthase reductase deficiency (CblE): A report of two patients and a
      novel mutation.
AB  - IMPORTANCE: Functional methionine synthase reductase deficiency, also known as
      cobalamin E disorder, is a rare autosomal recessive inherited disease that
      results in an impaired remethylation of homocysteine to methionine. It presents
      with macrocytic anemia, hyperhomocysteinemia, and hypomethioninemia, and may also
      be accompanied with neurological impairment. CLINICAL PRESENTATION: We describe
      two new cases of unrelated girls with megaloblastic anemia misclassified at first
      as congenital dyserythropoietic anemia with development of neurologic dysfunction
      in one of them. INTERVENTION: The posterior finding of biochemical features
      (hyperhomocysteinemia and hypomethioninemia) focused the diagnosis on the inborn
      errors of intracellular vitamin B12. Subsequent molecular analysis of the
      methionine synthase reductase (MTRR) gene revealed compound heterozygosity for a
      transition c.1361C > T (p.Ser454Leu) and another, not yet described in
      literature, c.1677-1G > A (p.Glu560fs) in one patient, and a single homozygosis
      mutation, c.1361C > T (p.Ser545Leu) in the other one. These mutations confirmed
      the diagnosis of cobalamin E deficiency. CONCLUSION: Treatment with
      hydroxocobalamin in combination with betaine appears to be useful for
      hematological improvement and prevention of brain disabilities in CblE-affected
      patients. Our study widens the clinical, molecular, metabolic, and cytological
      knowledge of deficiency MTRR enzyme.

PMID- 25978499
TI  - Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and
      Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana
      and Suriname.
AB  - Guyana and Suriname have made important progress in reducing the burden of
      malaria. While both countries use microscopy as the primary tool for clinical
      diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of
      the interior where laboratory support may be limited or unavailable. Recent
      reports indicate that histidine-rich protein 2 (PfHRP2)-based diagnostic tests
      specific for detection of P. falciparum may provide false negative results in
      some parts of South America due to the emergence of P. falciparum parasites that
      lack the pfhrp2 gene, and thus produce no PfHRP2 antigen. Pfhrp2 and pfhrp3 genes
      were amplified in parasite isolates collected from Guyana and Suriname to
      determine if there were circulating isolates with deletions in these genes.
      Pfhrp3 deletions were monitored because some monoclonal antibodies utilized in
      PfHRP2-based RDTs cross-react with the PfHRP3 protein. We found that all 97
      isolates from Guyana that met the inclusion criteria were both pfhrp2- and pfhrp3
      positive. In Suriname (N = 78), 14% of the samples tested were pfhrp2-negative
      while 4% were pfhrp3-negative. Furthermore, analysis of the genomic region
      proximal to pfhrp2 and pfhrp3 revealed that genomic deletions extended to the
      flanking genes. We also investigated the population substructure of the isolates
      collected to determine if the parasites that had deletions of pfhrp2 and pfhrp3
      belonged to any genetic subtypes. Cluster analysis revealed that there was no
      predominant P. falciparum population substructure among the isolates from either
      country, an indication of genetic admixture among the parasite populations.
      Furthermore, the pfhrp2-deleted parasites from Suriname did not appear to share a
      single, unique genetic background. 

PMID- 25978500
TI  - Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA.
AB  - Human cancer is caused by the interplay of mutations in oncogenes and tumor
      suppressor genes and inherited variations in cancer susceptibility genes. While
      many of the tumor initiating mutations are well characterized, the effect of
      genetic background variation on disease onset and progression is less understood.
      We have used C. elegans genetics to identify genetic modifiers of the oncogenic
      RAS/MAPK signaling pathway. Quantitative trait locus analysis of two highly
      diverged C. elegans isolates combined with allele swapping experiments identified
      the polymorphic monoamine oxidase A (MAOA) gene amx-2 as a negative regulator of
      RAS/MAPK signaling. We further show that the serotonin metabolite 5
      hydroxyindoleacetic acid (5-HIAA), which is a product of MAOA catalysis,
      systemically inhibits RAS/MAPK signaling in different organs of C. elegans. Thus,
      MAOA activity sets a global threshold for MAPK activation by controlling 5-HIAA
      levels. To our knowledge, 5-HIAA is the first endogenous small molecule that acts
      as a systemic inhibitor of RAS/MAPK signaling. 

PMID- 25978502
TI  - Solutions wanted.

PMID- 25978501
TI  - Flux Synthesis, Structure, Properties, and Theoretical Magnetic Study of
      Uranium(IV)-Containing A2USi6O15 (A = K, Rb) with an Intriguing Green-to-Purple,
      Crystal-to-Crystal Structural Transition in the K Analogue.
AB  - The flux growth of uranium(IV) oxides presents several challenges, and to the
      best of our knowledge, only one example has ever been reported. We succeeded in
      growing two new reduced uranium silicates A2USi6O15 (A = K, Rb) under flux growth
      conditions in sealed copper tubes. The compounds crystallize in a new structure
      type with space group C2/c and lattice parameters a = 24.2554(8) A, b = 7.0916(2)
      A, c = 17.0588(6) A, beta = 97.0860(6)  degrees  (K) and a = 24.3902(8) A, b =
      7.1650(2) A, c = 17.2715(6) A, beta = 96.8600(6)  degrees  (Rb). A2USi6O15 (A =
      K, Rb) are isocompositional to a previously reported Cs2USi6O15, and the two
      structures are compared. K2USi6O15 undergoes an interesting crystal-to-crystal
      structural phase transition at T ~ 225 K to a triclinic structure, which is
      accompanied by an intense color change. The magnetic properties of A2USi6O15 (A =
      K, Rb, Cs) are reported and differ from the magnetism observed in other U(4+)
      compounds. Calculations are performed on the (UO6)(-8) clusters of K2USi6O15 to
      study the cause of these unique magnetic properties. 

PMID- 25978503
TI  - Answers to your questions about chronic care management.

PMID- 25978504
TI  - ICD-10 Sprains, Strains, and Automobile Accidents.

PMID- 25978505
TI  - Treating dementia with shared group visits.

PMID- 25978506
TI  - How to provide more access without working more hours.

PMID- 25978510
TI  - Blood glucose tracker.

PMID- 25978514
TI  - Blinded by a Patient's Age.

PMID- 25978515
TI  - Ameliorating effects of Tamarindus indica fruit extract on anti-tubercular drugs
      induced liver toxicity in rats.
AB  - The study aimed to evaluate the hepatoprotective potential of aqueous extract of
      Tamarindus indica fruit against combination of two antitubercular drugs viz.
      Isoniazid and Rifampicin induced hepatotoxicity in rats. In vitro antioxidant
      activity of aqueous extract of T. indica by DPPH-HPLC method was found to be
      81.48%. Treatment with aqueous extract of T. indica significantly reduced the
      elevated levels of biochemical markers such as SGOT, SGPT, ALP, bilirubin, TBARS
      and increased the albumin level as well antioxidant activities of SOD, CAT and
      GSH in intoxicated rats. The biochemical changes were supported by histological
      observations. Results of this study clearly demonstrate that aqueous extract of
      T. indica fruit protects against anti tuberculosis induced oxidative liver damage
      in rats and thus possess significant hepatoprotective activity. Further, it could
      be suggested that supplementation with this food extract might prove beneficial
      in the individuals on anti-TB drugs. 

PMID- 25978516
TI  - Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic
      Glucoprivation in Male Rats.
AB  - Hindbrain catecholamine neurons are required for elicitation of feeding responses
      to glucose deficit, but the forebrain circuitry required for these responses is
      incompletely understood. Here we examined interactions of catecholamine and
      orexin neurons in eliciting glucoprivic feeding. Orexin neurons, located in the
      perifornical lateral hypothalamus (PeFLH), are heavily innervated by hindbrain
      catecholamine neurons, stimulate food intake, and increase arousal and behavioral
      activation. Orexin neurons may therefore contribute importantly to appetitive
      responses, such as food seeking, during glucoprivation. Retrograde tracing
      results showed that nearly all innervation of the PeFLH from the hindbrain
      originated from catecholamine neurons and some raphe nuclei. Results also
      suggested that many catecholamine neurons project collaterally to the PeFLH and
      paraventricular hypothalamic nucleus. Systemic administration of the
      antiglycolytic agent, 2-deoxy-D-glucose, increased food intake and c-Fos
      expression in orexin neurons. Both responses were eliminated by a lesion of
      catecholamine neurons innervating orexin neurons using the retrogradely
      transported immunotoxin, anti-dopamine-beta-hydroxylase saporin, which is
      specifically internalized by dopamine-beta-hydroxylase-expressing catecholamine
      neurons. Using designer receptors exclusively activated by designer drugs in
      transgenic rats expressing Cre recombinase under the control of tyrosine
      hydroxylase promoter, catecholamine neurons in cell groups A1 and C1 of the
      ventrolateral medulla were activated selectively by peripheral injection of
      clozapine-N-oxide. Clozapine-N-oxide injection increased food intake and c-Fos
      expression in PeFLH orexin neurons as well as in paraventricular hypothalamic
      nucleus neurons. In summary, catecholamine neurons are required for the
      activation of orexin neurons during glucoprivation. Activation of orexin neurons
      may contribute to appetitive responses required for glucoprivic feeding. 

PMID- 25978517
TI  - Accuracy of pulse oximeters in detecting hypoxemia in patients with chronic
      thromboembolic pulmonary hypertension.
AB  - PURPOSE: Pulse oximetry is routinely used to continuously and non-invasively
      monitor arterial oxygen saturation (SaO2). When oxygen saturation by pulse
      oximeter (SpO2) overestimates SaO2, hypoxemia may be overlooked. We compared the
      SpO2 - SaO2 differences among three pulse oximeters in patients with chronic
      thromboembolic pulmonary hypertension (CTEPH) who spent their daily lives in a
      poor oxygen state. MATERIAL AND METHOD: This prospective observational study
      recruited 32 patients with CTEPH undergoing elective cardiac catheterization. As
      we collected arterial blood samples in the catheter laboratory, SpO2 values were
      simultaneously recorded. Three pulse oximeters were used on each patient, and
      SpO2 values were compared with oximetry readings using a blood gas analyzer. To
      determine the optimal SpO2 value by which to detect hypoxemia (SaO2?90%), we
      generated receiver operating characteristic (ROC) curves for each pulse oximeter.
      RESULT: The root mean square of each pulse oximeter was 1.79 (OLV-3100), 1.64 (N
      BS), and 2.50 (Masimo Radical). The mean bias (SpO2 - SaO2) for the 90%-95%
      saturation range was significantly higher for Masimo Radical (0.19 +/- 1.78% [OLV
      3100], 0.18 +/- 1.63% [N-BS], and 1.61 +/- 1.91% [Masimo Radical]; p<0.0001). The
      optimal SpO2 value to detect hypoxemia (SaO2?90%) was 89% for OLV-3100, 90% for N
      BS, and 92% for Masimo Radical. CONCLUSION: We found that the biases and
      precision with which to detect hypoxemia differed among the three pulse
      oximeters. To avoid hypoxemia, the optimal SpO2 should be determined for each
      pulse oximeter.

PMID- 25978518
TI  - Correction: Quantitative Assessment of Antibody Internalization with Novel
      Monoclonal Antibodies against Alexa Fluorophores.

PMID- 25978519
TI  - Regulatory plasma cells.
AB  - B cells can regulate immunity negatively or positively. Identifying the B cell
      subsets mediating these antagonistic activities, and the molecular mechanisms
      governing their differentiation, might enable the development of novel approaches
      to target B cells therapeutically. The suppressive functions of B cells are
      primarily mediated through their production of interleukin (IL)-10 and IL-35.
      Recent studies have shown that distinct sets of IgM(+)CD19(+)CD138(hi) plasma
      cells were the major B cell subsets producing these cytokines in a regulatory
      manner in vivo during autoimmune and infectious diseases. This review summarizes
      current knowledge on these 'regulatory plasma cells', and discusses the emerging
      data showing that the mechanisms involved in their generation partly overlap with
      those controlling the differentiation of 'effector regulatory T cells'. 

PMID- 25978520
TI  - Nodulisporiviridins A-H, Bioactive Viridins from Nodulisporium sp.
AB  - Eight new viridins, nodulisporiviridins A-H (1-8), were isolated from the extract
      of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was
      fermented with potato-dextrose broth. The structures were determined using
      spectroscopic and X-ray crystallographic analysis. Nodulisporiviridins A-D (1-4)
      are unique viridins with an opened ring A. The Abeta42 aggregation inhibitory
      activities of 1-8 were evaluated using a thioflavin T (ThT) assay with
      epigallocatechin gallate (EGCG) as the positive control (EGCG IC50 of 0.5 MUM).
      Nodulisporiviridin G (7) displayed potent inhibitory activity with an IC50 value
      of 1.2 MUM, and the preliminary trend of activity of these viridins as Abeta42
      aggregation inhibitors was proposed. The short-term memory assay on an Abeta
      transgenic drosophila model of Alzheimer's disease showed that all eight
      compounds improved the short-term memory capacity, with potencies close to that
      of the positive control (memantine). 

PMID- 25978522
TI  - Relationship between Exposure to Household Humidifier Disinfectants and Risk of
      Lung Injury: A Family-Based Study.
AB  - BACKGROUND: In South Korea, a cluster of acute lung disease patients included
      lung injury disease suspected of being caused by the use of humidifier
      disinfectants. We examined the relationship between humidifier disinfectant
      exposure and clinically diagnosed humidifier disinfectant-associated lung injury
      (HDLI) in a family-based study. METHODS: This case-control study included 169
      clinically confirmed HDLI cases and 303 family controls who lived with the HDLI
      patients. A range of information on exposure to humidifier disinfectants was
      obtained using a structured questionnaire and field investigations. Odds ratios
      (ORs) and confidence intervals (CIs) were estimated using unconditional logistic
      regression models that were adjusted for age, sex, presence of a factory within 1
      km of residence, and the number of household chemical products used. RESULTS:
      HDLI risk increased approximately two-fold or more among the highest quartile
      compared with the lowest quartile in terms of the hours sleeping in a room with
      an operating humidifier treated with disinfectant (adjusted OR = 2.0, 95 % CI =
      1.1-3.7), average hours of disinfectant-treated humidifier use per day (adjusted
      OR = 2.1, 95 % CI = 1.0-4.5), airborne disinfectant intensity (adjusted OR = 2.6,
      95% CI = 1.2-5.3), and cumulative disinfectant inhalation level (adjusted OR =
      2.0, 95% CI = 1.0-4.1). HDLI risk increased as the distance of the bed from
      humidifier gets shorter; compared with longer distance (> 1 m), the odds ratio
      was 2.7 for 0.5 to 1 m (95 % CI = 1.5-5.1) and 13.2 for <0.5 m (95 % CI = 2.4
      73.0). CONCLUSIONS: The use of household humidifier disinfectants was associated
      with HDLI risk in a dose-response manner.

PMID- 25978521
TI  - A Clickable Aminooxy Probe for Monitoring Cellular ADP-Ribosylation.
AB  - ADP-ribosylation is essential for cell function, yet there is a dearth of methods
      for detecting this post-translational modification in cells. Here, we describe a
      clickable aminooxy alkyne (AO-alkyne) probe that can detect cellular ADP
      ribosylation on acidic amino acids following Cu-catalyzed conjugation to an azide
      containing reporter. Using AO-alkyne, we show that PARP10 and PARP11 are auto-ADP
      ribosylated in cells. We also demonstrate that AO-alkyne can be used to monitor
      stimulus-induced ADP-ribosylation in cells. Functional studies using AO-alkyne
      support a previously unknown mechanism for ADP-ribosylation on acidic amino
      acids, wherein a glutamate or aspartate at the initial C1'-position of ADP-ribose
      transfers to the C2' position. This new mechanism for ADP-ribosylation has
      important implications for how glutamyl/aspartyl-ADP-ribose is recognized by
      proteins in cells. 

PMID- 25978523
TI  - Toxicity and oxidative stress induced by semiconducting polymer dots in RAW264.7
      mouse macrophages.
AB  - The rapid development and acceptance of PDots for biological applications depends
      on an in depth understanding of their cytotoxicity. In this paper, we performed a
      comprehensive study of PDot cytotoxicity at both the gross cell effect level
      (such as cell viability, proliferation and necrosis) and more subtle effects
      (such as redox stress) on RAW264.7 cells, a murine macrophage cell line with high
      relevance to in vivo nanoparticle disposition. The redox stress measurements
      assessed were inner mitochondrial membrane lipid peroxidation (nonyl-acridine
      orange, NAO), total thiol level (monobromobimane, MBB), and pyridine nucleotide
      redox status (NAD(P)H autofluorescence). Because of the extensive work already
      performed with QDots on nanotoxicity and also because of their comparable size,
      QDots were chosen as a comparison/reference nanoparticle for this study. The
      results showed that PDots exhibit cytotoxic effects to a much lesser degree than
      their inorganic analogue (QDots) and are much brighter, allowing for much lower
      concentrations to be used in various biological applications. In addition, at
      lower dose levels (2.5 nM to 10 nM) PDot treatment resulted in higher total thiol
      level than those found with QDots. At higher dose levels (20 nM to 40 nM) QDots
      caused significantly higher thiol levels in RAW264.7 cells, than was seen with
      PDots, suggesting that QDots elicit compensation to oxidative stress by
      upregulating GSH synthesis. At the higher concentrations of QDots, NAD(P)H levels
      showed an initial depletion, then repletion to a level that was greater than
      vehicle controls. PDots showed a similar trend but this was not statistically
      significant. Because PDots elicit less oxidative stress and cytotoxicity at low
      concentrations than QDots, and because they exhibit superior fluorescence at
      these low concentrations, PDots are predicted to have enhanced utility in
      biomedical applications. 

PMID- 25978524
TI  - Assignment of Core versus Antenna Fucosylation Types in Protein N-Glycosylation
      via Procainamide Labeling and Tandem Mass Spectrometry.
AB  - Fucosylation is an important feature of protein N-glycosylation as it has been
      reported to influence the efficacy of therapeutic proteins and as a potential
      disease biomarker. A common approach for characterizing protein N-glycans is to
      analyze the native glycans via tandem mass spectrometry (MS). However, tandem MS
      analysis of native N-glycans typically results in proton migration, which in turn
      leads to fucose residue migration from the glycan core to the antenna and vice
      versa. This phenomenon ultimately leads to ambiguous assignment of N-glycan
      fucosylation. Although the use of specific fucosidases has been successfully
      employed for assigning fucosylation, such strategies are often too cumbersome,
      expensive, and time-consuming for routine N-glycan analysis. As an alternative,
      we explore the influence of labeling N-glycans with procainamide hydrochloride to
      inhibit fucose migration during tandem MS analysis. The labeled N-glycan pool was
      separated and analyzed using ultraperformance liquid chromatography and a
      hydrophobic interaction liquid chromatography column coupled to a quadrupole time
      of-flight mass spectrometer (UPLC-HILIC-QTOF-MS). The observation of the m/z
      587.3 core fucose diagnostic peak corresponding to [GlcNAc + Fucose +
      Procainamide + H](+) in the tandem MS data of fucosylated N-glycans rapidly
      verifies core fucosylation while its absence signifies antennae fucosylation.
      This unique approach is here validated with human IgG (for core fucosylation) and
      human alpha-1-acid-glycoprotein (for antenna fucosylation). We further present a
      useful application toward the rapid verification of fucosylation types in a
      therapeutic protein (Rituximab). 

PMID- 25978525
TI  - Infrared spectroscopic investigation of photoionization-induced acidic C-H bonds
      in cyclic ethers.
AB  - Infrared (IR) predissociation spectroscopy based on vacuum-ultraviolet
      photoionization detection is performed for the neutral and cationic
      tetrahydrofuran (THF) and tetrahydropyran (THP). The CH bonds in neutral THF and
      THP are regarded as aprotic, even though the CH bonds are weakened by the
      negative hyperconjugation. After 118 nm photoionization, however, the negative
      hyperconjugation changes to the positive hyperconjugation and their CH bond
      acidities remarkably increase. In the IR spectrum of the THF cation, an intense
      band is observed at ca. 2700 cm(-1). This band is assigned to the antisymmetric
      stretch vibration of the two CalphaH bonds next to the oxygen atom. The high
      intensity and low frequency of this band are due to the delocalization of the
      sigma electrons of the two CalphaH bonds to the singly occupied molecular orbital
      (SOMO) through the hyperconjugation. In the IR spectrum of the THP cation, on the
      other hand, the stretch bands of the CalphaH bonds do not show obvious low
      frequency shift and intensity enhancement, while the stretch band of the
      equatorial CgammaH bond, at the para-position to the oxygen atom, appears at 2855
      cm(-1) with high intensity. This acidity enhancement of the equatorial CgammaH
      bond is attributed to the mutiple hyperconjugation among the CgammaH bond, two
      CalphaCbeta bonds, and SOMO of the oxygen atom. These results suggest that the
      difference of the hyperconjugation mechanism between the THF and THP cations
      arises from their preferable conformations. 

PMID- 25978527
TI  - A general transformation to canonical form for potentials in pairwise interatomic
      interactions.
AB  - A generalized formulation of explicit force-based transformations is introduced
      to investigate the concept of a canonical potential in both fundamental chemical
      and intermolecular bonding. Different classes of representative ground electronic
      state pairwise interatomic interactions are referenced to a chosen canonical
      potential illustrating application of such transformations. Specifically,
      accurately determined potentials of the diatomic molecules H2, H2(+), HF, LiH,
      argon dimer, and one-dimensional dissociative coordinates in Ar-HBr, OC-HF, and
      OC-Cl2 are investigated throughout their bound potentials. Advantages of the
      current formulation for accurately evaluating equilibrium dissociation energies
      and a fundamentally different unified perspective on nature of intermolecular
      interactions will be emphasized. In particular, this canonical approach has
      significance to previous assertions that there is no very fundamental distinction
      between van der Waals bonding and covalent bonding or for that matter hydrogen
      and halogen bonds. 

PMID- 25978526
TI  - Global Association of Cold Spells and Adverse Health Effects: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: There is substantial evidence that mortality increases in low
      temperatures. Less is known about the role of prolonged cold periods denoted as
      cold spells. OBJECTIVE: We conducted the first systematic review and meta
      analysis to summarize the evidence on the adverse health effects of cold spells
      in varying climates. DATA SOURCES AND EXTRACTION: Four databases (Ovid Medline,
      PubMed, Scopus, Web of Science) were searched for all years and languages
      available. "Cold spell" was defined as an event below a temperature threshold
      lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26
      satisfied our eligibility criteria for the systematic review, and 9 were eligible
      for meta-analyses. The articles were grouped by the three main study questions
      into Overall-effect Group, Added-effect Group, and Temperature-change-effect
      Group. DATA SYNTHESIS: Based on random-effects models in the meta-analyses, cold
      spells were associated with increased mortality from all or all nonaccidental
      causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from
      five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates
      from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8
      estimates from four studies). Estimated associations were stronger for people >=
      65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0-64 years of age
      (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number
      of studies suggested an increased morbidity related to cold spells, but it was
      not possible to quantitatively summarize the evidence. CONCLUSIONS: Cold spells
      are associated with increased mortality rates in populations around the world.
      The body of evidence suggests that cold spells also have other adverse health
      effects. There was substantial heterogeneity among the studies, which should be
      taken into account in the interpretation of the results. CITATION: Ryti NR, Guo
      Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health
      effects: a systematic review and meta-analysis. Environ Health Perspect 124:12
      22; http://dx.doi.org/10.1289/ehp.1408104.

PMID- 25978528
TI  - Near-Field Imaging of Phased Array Metasurfaces.
AB  - Phased-antenna metasurfaces can impart abrupt, spatially dependent changes to the
      amplitude, phase, and polarization of light and thus mold wavefronts in a desired
      fashion. Here we present an experimental and computational near-field study of
      metasurfaces based on near-resonant V-shaped antennas and connect their near- and
      far-field optical responses. We show that far fields can be obtained from
      limited, experimentally obtained knowledge of the near fields, paving the way for
      experimental near-field characterization of metasurfaces and other optical
      nanostructures and prediction of their far fields from the near-field
      measurements. 

PMID- 25978530
TI  - van der Waals forces in density functional theory: a review of the vdW-DF method.
AB  - A density functional theory (DFT) that accounts for van der Waals (vdW)
      interactions in condensed matter, materials physics, chemistry, and biology is
      reviewed. The insights that led to the construction of the Rutgers-Chalmers van
      der Waals density functional (vdW-DF) are presented with the aim of giving a
      historical perspective, while also emphasizing more recent efforts which have
      sought to improve its accuracy. In addition to technical details, we discuss a
      range of recent applications that illustrate the necessity of including
      dispersion interactions in DFT. This review highlights the value of the vdW-DF
      method as a general-purpose method, not only for dispersion bound systems, but
      also in densely packed systems where these types of interactions are
      traditionally thought to be negligible. 

PMID- 25978529
TI  - The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and
      Its Ability to Identify Primary Non Function.
AB  - Donation after cardiac death (DCD) livers are marginal organs for transplant and
      their use is associated with a higher risk of primary non function (PNF) or early
      graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to
      discriminate between DCD livers of varying clinical outcome. DCD groups were
      categorized as PNF retransplanted within a week (n=7), good functional outcome
      (n=7) peak aspartate transaminase (AST) <= 1000 IU/L and EGD (n=9) peak AST >=
      2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru
      cut liver biopsies. High throughput expression analysis was performed using miRNA
      arrays. Bioinformatics for expression data analysis was performed and validated
      with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was
      investigated using computational biology prediction algorithms. From the array
      analysis 16 miRNAs were identified as significantly different (p<0.05). On RT
      qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical
      groups. Only one miRNA, miR-22, was validated with marginal significance, to have
      differential expression between the three groups (p=0.049). From computational
      biology miR-22 was predicted to affect signalling pathways that impact protein
      turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression
      patterns have a low diagnostic potential clinically in discriminating DCD liver
      quality and outcome. 

PMID- 25978531
TI  - Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex:
      case report.
AB  - The authors report the case of a 14-year-old male with a subependymal giant cell
      astrocytoma (SEGA) that occurred in the absence of tuberous sclerosis complex
      (TSC). The patient presented with progressive headache and the sudden onset of
      nausea and vomiting. Neuroimaging revealed an enhancing left ventricular mass
      located in the region of the foramen of Monro with significant mass effect and
      midline shift. The lesion had radiographic characteristics of SEGA; however, the
      diagnosis remained unclear given the absence of clinical features of TSC. The
      patient underwent gross-total resection of the tumor with resolution of his
      symptoms. Although tumor histology was consistent with SEGA, genetic analysis of
      both germline and tumor DNA revealed no TSC1/2 mutations. Similarly, a
      comprehensive clinical evaluation failed to reveal any clinical features
      characteristic of TSC. Few cases of SEGA without clinical or genetic evidence of
      TSC have been reported. The histogenesis, genetics, and clinical approach to this
      rare lesion are briefly reviewed. 

PMID- 25978532
TI  - Baclofen overdose from possible intrinsic malfunction of SynchroMed II pump.
AB  - This is a case report illustrating an overdose of baclofen in a 10-year-old boy
      due to a likely malfunction of a SynchroMed II pump. This ultimately necessitated
      a pump replacement. One-year follow-up showed no further incidents of baclofen
      overdose, with multiple pump refills. 

PMID- 25978533
TI  - Ectopic cilia associated with an orbital dermoid cyst and sinus tract: case
      report.
AB  - Ectopic cilia are extremely rare congenital anomalies in which eyelash follicles
      appear in an abnormal place on the eyelid, most typically on the lateral quadrant
      of the anterior surface of the upper eyelid. In the majority of cases, simple
      surgical excision of ectopic cilia is indicated because of its cosmetic aspect.
      There is usually no associated medical co-morbidity with this anomaly. The
      authors report an unusual case of ectopic cilia associated with an orbital
      dermoid cyst and sinus tract. A 3-year-old boy was initially diagnosed with
      ectopic cilia on the left upper eyelid. There was no history of inflammation or
      swelling of the eyelid. An ophthalmological examination revealed only 1 mm of
      ptosis; no proptosis, inferior displacement, or palpable orbital mass was
      present. During surgical excision of the ectopic cilia, a thin sinus tract was
      identified, leading posteriorly to the orbit. Magnetic resonance imaging
      performed after the excision showed a supraorbital extraconal mass just below the
      roof of the left orbit. A supraorbital 2-piece craniotomy was performed with
      total extirpation of the dermoid cyst. The cyst was removed en bloc without
      damage to the extraocular muscles, but the sinus tract could no longer be
      identified. Follow-up MRI was performed 6 months after surgery and showed no
      evidence of recurrence. A follow-up ophthalmological examination showed no signs
      of inferior displacement or proptosis. To the best of the authors' knowledge,
      this case is the first reported instance of ectopic cilia associated with a
      dermoid cyst and sinus tract in which no typical clinical signs and symptoms of
      possible orbital pathology were present. This case highlights the value of
      radiological examination in all cases of ectopic cilia prior to surgical
      excision. 

PMID- 25978534
TI  - Clinical benefits of diffusion tensor imaging in hydrocephalus.
AB  - OBJECT The object of this study was to use diffusion tensor imaging (DTI) to
      evaluate and characterize white matter changes in hydrocephalus. METHODS The
      authors performed a retrospective analysis of DTI in a cohort of patients with
      hydrocephalus (n = 35), 19 of whom had both pre- and postsurgical imaging
      studies. These patient's DTI values were compared with values extracted from age
      dependent trend lines computed from a healthy subject group (n = 70, age span 14
      months-14 years). Several DTI parameters in different regions of interest (ROIs)
      were evaluated to find the most sensitive parameters for clinical decision making
      in hydrocephalus. RESULTS Compared with healthy controls, patients with active
      hydrocephalus had a statistically significant change in all DTI parameters. The
      most sensitive and specific DTI parameter for predicting hydrocephalus was axial
      diffusivity (lambda1) measured at the level of the corona radiata. Diffusion
      tensor imaging parameters correlated with several conventional radiological
      parameters in the assessment of hydrocephalus but were not superior to them.
      There was no convincing correlation between clinical disease severity and DTI
      parameters. When examining the pre- and postsurgical effect, it was found that
      DTI may be a sensitive tool for estimating tissue improvement. CONCLUSIONS This
      large-cohort study with a multidisciplinary approach combining clinical,
      neurological, radiological, and multiple DTI parameters revealed the most
      sensitive DTI parameters for identifying hydrocephalus and suggested that they
      may serve as an important tool for the disorder's quantitative radiological
      assessment. 

PMID- 25978535
TI  - Transosseous cerebrospinal fluid fistula 14 years after Chiari decompression:
      presentation and management.
AB  - The authors report a unique case of a transosseous CSF fistula that was detected
      more than 10 years after treatment of a symptomatic Chiari I malformation. This
      lesion initially presented as an intraosseous cystic lesion involving the C-2
      vertebra, which was found to communicate freely with the subarachnoid space
      through a tiny dural opening. Surgical management involved hemilaminectomy and
      repair of the dural defect followed by reinforcement of the bony defect with
      demineralized bone matrix. Following closure of the fistula, symptoms of elevated
      intracranial pressure developed, necessitating a ventriculoperitoneal shunt for
      CSF diversion. 

PMID- 25978536
TI  - Interleukin-1beta Level Is Increased in Vitreous of Patients with Neovascular Age
      Related Macular Degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV).
AB  - PURPOSE: To examine the expression of pro-interleukin-1beta (pro-IL-1beta) and
      interleukin-1beta (IL-1beta) in the vitreous body of patients with neovascular
      age-related macular degeneration(nAMD), polypoidal choroidal vasculopathy (PCV),
      proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO) or Eales'
      disease to further elucidate the role of IL-1beta and inflammation in the
      pathogenesis of neovascular retinal disease. DESIGN: Prospective clinical
      laboratory investigation study. METHODS: All patients enrolled had vitreous
      hemorrhage due to nAMD, PCV, PDR, RVO or Eales' disease that required vitrectomy.
      Patients were excluded for any history of active intraocular inflammation, or
      other ophthalmic surgery besides vitrectomy. Control samples were obtained from
      patients with idiopathic macular epiretinal membrane. A total of fifty vitreous
      samples were collected from patient during vitrectomy. Pro-IL-1beta and IL-1beta
      expression were measured by enzyme-linked immunosorbent assay (ELISA). Results
      were analyzed statistically using nonparametric tests. RESULTS: Expression of pro
      IL-1beta protein was increased by 2.83-fold and 9.19-fold in PCV and nAMD
      vitreous samples relative to control, respectively. Expression of IL-beta protein
      was increased by 10-fold and 4.83-fold in PCV and nAMD vitreous samples relative
      to control, respectively. CONCLUSIONS: Our results demonstrate that expression of
      pro-IL-1beta and IL-1beta proteins is higher in PCV and nAMD. The roles of pro-IL
      1beta and IL-1beta as inflammatory mediators in the development of PCV and nAMD
      may be associated with photoreceptor degeneration and neovascularization which
      necessitates further study.

PMID- 25978538
TI  - Adaptation and Evaluation of Online Self-learning Modules to Teach Critical
      Appraisal and Evidence-Based Practice in Nursing: An International Collaboration.
AB  - Healthcare professionals need to update their knowledge and acquire skills to
      continually inform their practice based on scientific evidence. This study was
      designed to evaluate online self-learning modules on critical appraisal skills to
      promote the use of research in clinical practice among nurses from Quebec
      (Canada) and the Basque Country (Spain). The teaching material was developed in
      Quebec and adapted to the Basque Country as part of an international
      collaboration project. A prospective pre-post study was conducted with 36 nurses
      from Quebec and 47 from the Basque Country. Assessment comprised the
      administration of questionnaires before and after the course in order to explore
      the main intervention outcomes: knowledge acquisition and self-learning
      readiness. Satisfaction was also measured at the end of the course. Two of the
      three research hypotheses were confirmed: (1) participants significantly improved
      their overall knowledge score after the educational intervention; and (2) they
      were, in general, satisfied with the course, giving it a rating of seven out of
      10. Participants also reported a greater readiness for self-directed learning
      after the course, but this result was not significant in Quebec. The study
      provides unique knowledge on the cultural adaptation of online self-learning
      modules for teaching nurses about critical appraisal skills and evidence-based
      practice. 

PMID- 25978537
TI  - Might Video Games Help Remedy Childhood Obesity?

PMID- 25978539
TI  - Phenotypic Knockout of CXCR4 Expression by a Novel Intrakine Mutant hSDF
      1alpha/54/KDEL Inhibits Breast Cancer Metastasis.
AB  - Many malignant tumors express high levels of the chemokine receptor CXCR4, and
      the interaction between CXCR4 and its ligand, SDF-1, promotes migration,
      invasion, and metastasis of breast cancer cells. Therefore, blocking the
      interaction between CXCR4 and SDF-1 could alter the tumor's metastatic phenotype
      and control the development and progression of cancers. We used a cellular
      phenotypic knockout strategy and developed a novel recombinant gene, AdSDF
      1alpha/54/KDEL, which contains an adenovirus vector, a mutant form of SDF-1 that
      lacks a C-terminal alpha-helix, and a KDEL tetrapeptide sequence that promotes
      retention at the endoplasmic reticulum (ER). We hypothesized that SDF
      1alpha/54/KDEL could efficiently block metastasis of breast cancer cells with
      less inflammatory side effects than SDF-1alpha/KDEL. Using the MCF-7 cell line,
      which expresses a stable, high level of CXCR4, we found that SDF-1alpha/54/KDEL
      efficiently becomes localized at the ER of tumor cells, where it specifically
      binds to newly synthesized CXCR4 and prevents it from reaching the cell surface.
      Chemotaxis and invasion assays revealed that the cells treated with SDF
      1alpha/54/KDEL failed to migrate toward SDF-1. We also found that SDF
      1alpha/54/KDEL impaired lung metastasis of metastatic breast cancer by decreasing
      CXCR4 on the cell surface. The novel recombinant gene, SDF-1alpha/54/KDEL, played
      an instrumental role in blocking SDF-1/CXCR4-mediated cell migration, and we
      found that this gene-based strategy for targeting the SDF-1/CXCR4 axis offers a
      very effective alternative method for preventing metastasis of breast cancer and
      other cancers expressing high levels of CXCR4. 

PMID- 25978540
TI  - An Abbreviated Montreal Cognitive Assessment (MoCA) for Dementia Screening.
AB  - OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a cognitive screening
      instrument growing in popularity, but few studies have conducted psychometric
      item analyses or attempted to develop abbreviated forms. We sought to derive and
      validate a short-form MoCA (SF-MoCA) and compare its classification accuracy to
      the standard MoCA and Mini-Mental State Examination (MMSE) in mild cognitive
      impairment (MCI), Alzheimer disease (AD), and normal aging. METHODS: 408 subjects
      (MCI n = 169, AD n = 87, and normal n = 152) were randomly divided into
      derivation and validation samples. Item analysis in the derivation sample
      identified most sensitive MoCA items. Receiver Operating Characteristic (ROC)
      analyses were used to develop cut-off scores and evaluate the classification
      accuracy of the SF-MoCA, standard MoCA, and MMSE. Net Reclassification
      Improvement (NRI) analyses and comparison of ROC curves were used to compare
      classification accuracy of the three measures. RESULTS: Serial subtraction
      (Cramer's V = .408), delayed recall (Cramer's V = .702), and orientation items
      (Cramer's V = .832) were included in the SF-MoCA based on largest effect sizes in
      item analyses. Results revealed 72.6% classification accuracy of the SF-MoCA,
      compared with 71.9% for the standard MoCA and 67.4% for the MMSE. Results of NRI
      analyses and ROC curve comparisons revealed that classification accuracy of the
      SF-MoCA was comparable to the standard version and generally superior to the
      MMSE. CONCLUSIONS: Findings suggest the SF-MoCA could be an effective brief tool
      in detecting cognitive impairment.

PMID- 25978542
TI  - Naming and functions of ACR2, arsenate reductase, and ACR3 arsenite efflux
      transporter in plants (correspondence on: Kumar, S., Dubey, R.S., Tripathi, R.D.,
      Chakrabarty, D., Trivedi, P.K., 2015. Omics and biotechnology of arsenic stress
      and detoxification in plants: current updates and prospective. Environ Int.
      74:221-230.).

PMID- 25978541
TI  - Quantitative risk stratification of oral leukoplakia with exfoliative cytology.
AB  - Exfoliative cytology has been widely used for early diagnosis of oral squamous
      cell carcinoma (OSCC). Test outcome is reported as "negative", "atypical"
      (defined as abnormal epithelial changes of uncertain diagnostic significance),
      and "positive" (defined as definitive cellular evidence of epithelial dysplasia
      or carcinoma). The major challenge is how to properly manage the "atypical"
      patients in order to diagnose OSCC early and prevent OSCC. In this study, we
      collected exfoliative cytology data, histopathology data, and clinical data of
      normal subjects (n=102), oral leukoplakia (OLK) patients (n=82), and OSCC
      patients (n=93), and developed a data analysis procedure for quantitative risk
      stratification of OLK patients. This procedure involving a step called expert
      guided data transformation and reconstruction (EdTAR) which allows automatic data
      processing and reconstruction and reveals informative signals for subsequent risk
      stratification. Modern machine learning techniques were utilized to build
      statistical prediction models on the reconstructed data. Among the several models
      tested using resampling methods for parameter pruning and performance evaluation,
      Support Vector Machine (SVM) was found to be optimal with a high sensitivity
      (median>0.98) and specificity (median>0.99). With the SVM model, we constructed
      an oral cancer risk index (OCRI) which may potentially guide clinical follow-up
      of OLK patients. One OLK patient with an initial OCRI of 0.88 developed OSCC
      after 40 months of follow-up. In conclusion, we have developed a statistical
      method for qualitative risk stratification of OLK patients. This method may
      potentially improve cost-effectiveness of clinical follow-up of OLK patients, and
      help design clinical chemoprevention trial for high-risk populations. 

PMID- 25978543
TI  - Altitudinal patterns of diversity and functional traits of metabolically active
      microorganisms in stream biofilms.
AB  - Resources structure ecological communities and potentially link biodiversity to
      energy flow. It is commonly believed that functional traits (generalists versus
      specialists) involved in the exploitation of resources depend on resource
      availability and environmental fluctuations. The longitudinal nature of stream
      ecosystems provides changing resources to stream biota with yet unknown effects
      on microbial functional traits and community structure. We investigated the
      impact of autochthonous (algal extract) and allochthonous (spruce extract)
      resources, as they change along alpine streams from above to below the treeline,
      on microbial diversity, community composition and functions of benthic biofilms.
      Combining bromodeoxyuridine labelling and 454 pyrosequencing, we showed that
      diversity was lower upstream than downstream of the treeline and that community
      composition changed along the altitudinal gradient. We also found that,
      especially for allochthonous resources, specialisation by biofilm bacteria
      increased along that same gradient. Our results suggest that in streams below the
      treeline biofilm diversity, specialisation and functioning are associated with
      increasing niche differentiation as potentially modulated by divers allochthonous
      and autochthonous constituents contributing to resources. These findings expand
      our current understanding on biofilm structure and function in alpine streams. 

PMID- 25978544
TI  - Temporal variation overshadows the response of leaf litter microbial communities
      to simulated global change.
AB  - Bacteria and fungi drive the decomposition of dead plant biomass (litter), an
      important step in the terrestrial carbon cycle. Here we investigate the
      sensitivity of litter microbial communities to simulated global change (drought
      and nitrogen addition) in a California annual grassland. Using 16S and 28S rDNA
      amplicon pyrosequencing, we quantify the response of the bacterial and fungal
      communities to the treatments and compare these results to background, temporal
      (seasonal and interannual) variability of the communities. We found that the
      drought and nitrogen treatments both had significant effects on microbial
      community composition, explaining 2-6% of total compositional variation. However,
      microbial composition was even more strongly influenced by seasonal and annual
      variation (explaining 14-39%). The response of microbial composition to drought
      varied by season, while the effect of the nitrogen addition treatment was
      constant through time. These compositional responses were similar in magnitude to
      those seen in microbial enzyme activities and the surrounding plant community,
      but did not correspond to a consistent effect on leaf litter decomposition rate.
      Overall, these patterns indicate that, in this ecosystem, temporal variability in
      the composition of leaf litter microorganisms largely surpasses that expected in
      a short-term global change experiment. Thus, as for plant communities, future
      microbial communities will likely be determined by the interplay between rapid,
      local background variability and slower, global changes. 

PMID- 25978545
TI  - High molecular weight dissolved organic matter enrichment selects for
      methylotrophs in dilution to extinction cultures.
AB  - The role of bacterioplankton in the cycling of marine dissolved organic matter
      (DOM) is central to the carbon and energy balance in the ocean, yet there are few
      model organisms available to investigate the genes, metabolic pathways, and
      biochemical mechanisms involved in the degradation of this globally important
      carbon pool. To obtain microbial isolates capable of degrading semi-labile DOM
      for growth, we conducted dilution to extinction cultivation experiments using
      seawater enriched with high molecular weight (HMW) DOM. In total, 93 isolates
      were obtained. Amendments using HMW DOM to increase the dissolved organic carbon
      concentration 4x (280 MUM) or 10x (700 MUM) the ocean surface water
      concentrations yielded positive growth in 4-6% of replicate dilutions, whereas
      <1% scored positive for growth in non-DOM-amended controls. The majority (71%) of
      isolates displayed a distinct increase in cell yields when grown in increasing
      concentrations of HMW DOM. Whole-genome sequencing was used to screen the culture
      collection for purity and to determine the phylogenetic identity of the isolates.
      Eleven percent of the isolates belonged to the gammaproteobacteria including
      Alteromonadales (the SAR92 clade) and Vibrio. Surprisingly, 85% of isolates
      belonged to the methylotrophic OM43 clade of betaproteobacteria, bacteria thought
      to metabolically specialize in degrading C1 compounds. Growth of these isolates
      on methanol confirmed their methylotrophic phenotype. Our results indicate that
      dilution to extinction cultivation enriched with natural sources of organic
      substrates has a potential to reveal the previously unsuspected relationships
      between naturally occurring organic nutrients and the microorganisms that consume
      them.

PMID- 25978547
TI  - Differences in emotion modulation using cognitive reappraisal in individuals with
      and without suicidal ideation: An ERP study.
AB  - Difficulties in emotion regulation have been associated with increased suicidal
      thoughts and behaviours. The majority of studies have examined self-reported use
      of emotion regulation strategies. In contrast, the current study focused on a
      direct measure of individuals' ability to use a specific emotion regulation
      strategy, cognitive reappraisal, using the late positive potential (LPP), an
      event-related potential component that reflects attention to emotional stimuli.
      Specifically, the cognitive reappraisal ability of 33 undergraduate students was
      assessed via an image-viewing task during which the participants had to passively
      view, increase or reduce their emotions in response to looking at neutral,
      positive or dysphoric images. We found that participants with a history of
      suicidal ideation (SI) had significantly higher LPP when asked to reduce negative
      emotion in response to dysphoric images, compared to individuals with no history
      of SI. These findings suggest that difficulties with using cognitive reappraisal,
      specifically to decrease negative affect, might be linked to suicide risk.

PMID- 25978546
TI  - Elemental sulfur and acetate can support life of a novel strictly anaerobic
      haloarchaeon.
AB  - Archaea domain is comprised of many versatile taxa that often colonize extreme
      habitats. Here, we report the discovery of strictly anaerobic extremely
      halophilic euryarchaeon, capable of obtaining energy by dissimilatory reduction
      of elemental sulfur using acetate as the only electron donor and forming sulfide
      and CO2 as the only products. This type of respiration has never been observed in
      hypersaline anoxic habitats and is the first example of such metabolic capability
      in the entire Archaea domain. We isolated and cultivated these unusual organisms,
      selecting one representative strain, HSR2, for detailed characterization. Our
      studies including physiological tests, genome sequencing, gene expression,
      metabolomics and [(14)C]-bicarbonate assimilation assays revealed that HSR2
      oxidized acetate completely via the tricarboxylic acid cycle. Anabolic
      assimilation of acetate occurred via activated glyoxylate bypass and anaplerotic
      carboxylation. HSR2 possessed sulfurtransferase and an array of membrane-bound
      polysulfide reductase genes, all of which were expressed during the growth. Our
      findings suggest the biogeochemical contribution of haloarchaea in hypersaline
      anoxic environments must be reconsidered. 

PMID- 25978548
TI  - Genome-wide transcriptome profiling provides insights into floral bud development
      of summer-flowering Camellia azalea.
AB  - The transition from vegetative to reproductive growth in woody perennials
      involves pathways controlling flowering timing, bud dormancy and outgrowth in
      responses to seasonal cues. However little is known about the mechanism governing
      the adaptation of signaling pathways to environmental conditions in trees.
      Camellia azalea is a rare species in this genus flowering during summer, which
      provides a unique resource for floral timing breeding. Here we reported a
      comprehensive transcriptomics study to capture the global gene profiles during
      floral bud development in C. azalea. We examined the genome-wide gene expression
      between three developmental stages including floral bud initiation, floral organ
      differentiation and bud outgrowth, and identified nine co-expression clusters
      with distinctive patterns. Further, we identified the differential expressed
      genes (DEGs) during development and characterized the functional properties of
      DEGs by Gene Ontology analysis. We showed that transition from floral bud
      initiation to floral organ differentiation required changes of genes in flowering
      timing regulation, while transition to floral bud outgrowth was regulated by
      various pathways such as cold and light signaling, phytohormone pathways and
      plant metabolisms. Further analyses of dormancy associated MADS-box genes
      revealed that SVP- and AGL24- like genes displayed distinct expression patterns
      suggesting divergent roles during floral bud development. 

PMID- 25978549
TI  - Silk Hydrogels of Tunable Structure and Viscoelastic Properties Using Different
      Chronological Orders of Genipin and Physical Cross-Linking.
AB  - Catering the hydrogel manufacturing process toward defined viscoelastic
      properties for intended biomedical use is important to hydrogel scaffolding
      function and cell differentiation. Silk fibroin hydrogels may undergo "physical"
      cross-linking through beta-sheet crystallization during high pressure carbon
      dioxide treatment, or covalent "chemical" cross-linking by genipin. We
      demonstrate here that time-dependent mechanical properties are tunable in silk
      fibroin hydrogels by altering the chronological order of genipin cross-linking
      with beta-sheet formation. Genipin cross-linking before beta-sheet formation
      affects gelation mechanics through increased molecular weight, affecting gel
      morphology, and decreasing stiffness response. Alternately, genipin cross-linking
      after gelation anchored amorphous regions of the protein chain, and increasing
      stiffness. These differences are highlighted and validated through large
      amplitude oscillatory strain near physiologic levels, after incorporation of
      material characterization at molecular and micron length scales. 

PMID- 25978551
TI  - Efficient polymer solar cells enabled by low temperature processed ternary metal
      oxide as electron transport interlayer with large stoichiometry window.
AB  - Highly efficient organic photovoltaic cells are demonstrated by incorporating low
      temperature solution processed indium zinc oxide (IZO) as cathode interlayers.
      The IZOs are synthesized using a combustion synthesis method, which enables low
      temperature processes (150-250  degrees C). We investigated the IZO films with
      different electron mobilities (1.4*10(-3) to 0.23 cm2/(V.s)), hydroxide-oxide
      content (38% to 47%), and surface roughness (0.19-5.16 nm) by modulating the
      ternary metal oxide stoichiometry. The photovoltaic performance was found to be
      relatively insensitive to the composition ratio of In:Zn over the range of
      0.8:0.2 to 0.5:0.5 despite the differences in their electrical and surface
      properties, achieving high power conversion efficiencies of 6.61%-7.04%. Changes
      in composition ratio of IZO do not lead to obvious differences in energy levels,
      diode parameters and morphology of the photoactive layer, as revealed by
      ultraviolet photoelectron spectroscopy (UPS), dark current analysis and time-of
      flight secondary ion mass spectrometry (TOF-SIMS) measurements, correlating well
      with the large IZO stoichiometry window that enables efficient photovoltaic
      devices. Our results demonstrate the robustness of this ETL system and provide a
      convenient approach to realize a wide range of multicomponent oxides and
      compatible with processing on flexible plastic substrates.

PMID- 25978552
TI  - The annual supplement to the Annals of Plastic Surgery of the Southeastern
      Society Annual Meeting 2014.

PMID- 25978550
TI  - Influence of self-reported chronic rhinosinusitis on health-related quality of
      life: a population-based survey.
AB  - Chronic rhinosinusitis (CRS) is a frequently occurring chronic respiratory
      disease. There is evidence that effective treatment of CRS can improve patients'
      quality of life, but the data regarding the extent to which CRS impairs patients'
      quality of life (QoL) is sparse. This study aimed to evaluate the effect of self
      reported CRS on health-related QoL and to determine whether the influence was
      associated with gender, age and socio-economic status. A four-stage random
      sampling method was used to select the participants from the general population
      in Guangzhou, China. All participants were interviewed face-to-face at their
      homes using a standardized questionnaire. The health-related QoL of each
      participant was assessed using the SF-36 Health Survey. The scores of the SF-36
      after adjusting for gender, age, socioeconomic conditions, smoking and some
      important comorbid conditions were compared between the CRS group and the non-CRS
      group using analysis of covariance. A multiple linear regression model with
      interaction terms was established to determine whether CRS affected QoL to the
      same degree across the different subpopulations. Among a total of 1,411
      participants aged at least 15 years, 118 persons (8.4%) had self-reported CRS.
      Subjects with CRS had an increased prevalence of allergic rhinitis, chronic
      obstructive pulmonary disease and gout than subjects without CRS. The CRS group
      had lower scores in all eight domains and the physical and mental component
      summary than those without CRS (P<0.05), and the greatest differences were in
      role emotional function (RE), general health (GH) and role physical function
      (RP). The impairments of the CRS participants in RE and RP were greater among the
      females than the males. Moreover, physical domains were affected to greater
      degrees among the elderly and those with high-level education. In conclusion, CRS
      is a common chronic disorder. Persons with self-reported CRS perceived themselves
      as having impaired QoL in both the physical and mental domains. These findings
      shed new light on the health burden of CRS and should be taken into account by
      clinicians involved in the care of CRS patients. 

PMID- 25978553
TI  - Vacuum-assisted closure therapy to the brain: a safe method for wound
      temporization in composite scalp and calvarial defects.
AB  - BACKGROUND: When composite scalp and calvarial defects with dural or cortical
      brain exposure are encountered, active infection or indeterminate oncologic
      margins complicate the timing of scalp reconstruction. The purpose of this study
      was to evaluate the safety and efficacy of vacuum-assisted closure (VAC) therapy
      as a temporizing measure in these complex scalp defects with dural or cortical
      brain exposure and a hostile local wound environment. METHODS: From December 2012
      to December 2013, all composite scalp and calvarial defects reconstructed by the
      senior author (D.S.) were reviewed and 10 cases were identified. Five of these
      cases were temporized with VAC therapy. The medical records of these patients
      were reviewed. RESULTS: Five patients (mean age, 66.2 years) with composite scalp
      and calvarial defects were temporized with VAC therapy. The indications for delay
      included gross wound infection in 4 patients and an indeterminate intraoperative
      oncologic margin. The average size of the scalp and calvarial defects measured
      123 and 49 cm, respectively. One patient underwent VAC therapy over exposed
      cortical brain with a dural defect measuring 25 cm. The average time between the
      initial operation and definitive reconstruction was 4.8 days. The average daily
      VAC output was 74 mL. Reconstructive methods included 1 free flap, 2 scalp
      rotational advancement flaps, and readvancement of 2 prior free flaps. At an
      average follow-up of 32 weeks, 1 patient developed a subcentimeter postoperative
      wound breakdown that was treated successfully with an incisional VAC.
      CONCLUSIONS: We found the use of VAC therapy applied directly to the dura or
      cortical brain as a safe and effective technique for short-term wound
      temporization in the setting of indeterminate oncologic margins or active
      infection.

PMID- 25978554
TI  - Nerve Transfers in the Upper Extremity: A Practical User's Guide.
AB  - Nerve injuries above the elbow are associated with a poor prognosis, even with
      prompt repair and appropriate rehabilitation. The past 2 decades have seen the
      development of numerous nerve transfer techniques, by which a denervated
      peripheral target is reinnervated by a healthy donor nerve. Nerve transfers are
      indicated in proximal brachial plexus injuries where grafting is not possible or
      in proximal injuries of peripheral nerves with long reinnervation distances.
      Nerve transfers represent a revolution in peripheral nerve surgery and offer the
      potential for superior functional recovery in severe nerve injuries. However, the
      techniques have not been universally adopted due in part to a misconception that
      nerve transfers can only be understood and performed by superspecialists. Nerve
      transfer procedures are not technically difficult and require no specialized
      equipment. Numerous transfers have been described, but there are a handful of
      transfers for which there is strong clinical evidence. To restore shoulder
      abduction and external rotation in upper trunk brachial plexus injury, the key
      transfers are the spinal accessory to suprascapular nerve and the medial triceps
      branch to axillary nerve. For elbow flexion, the flexor carpi ulnaris branch of
      ulnar nerve to the biceps and brachialis branches of the musculocutaneous nerve
      is the key transfer. For ulnar intrinsic function, the distal anterior
      interosseous nerve to ulnar motor branch transfer has yielded excellent
      functional results. Nerve transfers form a therapeutic triad with traditional
      tendon transfers and functional motor unit rehabilitation which, when applied
      appropriately, can yield excellent functional results in complex nerve injuries.
      Nerve transfers are a powerful yet underused tool for proximal nerve injuries,
      which offer hope for traditionally discouraging injuries. 

PMID- 25978555
TI  - Determination of thermodynamic potentials and the aggregation number for micelles
      with the mass-action model by isothermal titration calorimetry: A case study on
      bile salts.
AB  - The aggregation number (n), thermodynamic potentials (DeltaG, DeltaH, DeltaS) and
      critical micelle concentration (CMC) for 6 natural bile salts were determined on
      the basis of both original and previously published isothermal titration
      calorimetry (ITC) data. Different procedures to estimate parameters of micelles
      with ITC were compared to a mass-action model (MAM) of reaction type: n?S?Mn.
      This analysis can provide guidelines for future ITC studies of systems behaving
      in accordance with this model such as micelles and proteins that undergo self
      association to oligomers. Micelles with small aggregation numbers, as those of
      bile salts, are interesting because such small aggregates cannot be characterized
      as a separate macroscopic phase and the widely applied pseudo-phase model (PPM)
      is inaccurate. In the present work it was demonstrated that the aggregation
      number of micelles was constant at low concentrations enabling determination of
      the thermodynamic potentials by the MAM. A correlation between the aggregation
      number and the heat capacity was found, which implies that the dehydrated surface
      area of bile salts increases with the aggregation number. This is in accordance
      with Tanford's principles of opposing forces where neighbouring molecules in the
      aggregate are better able to shield from the surrounding hydrophilic environment
      when the aggregation number increases. 

PMID- 25978556
TI  - Creation of giant two-dimensional crystal of zinc oxide nanodisk by method of
      single-particle layer of organo-modified inorganic fine particles.
AB  - In this study, the formation and structure of a single-particle layer of organo
      zinc oxide are investigated using surface-pressure-area (pi-A) isotherms, out-of
      plane X-ray diffraction (XRD) analysis, and atomic force microscopy (AFM).
      Further, techniques for achieving the solubilization of inorganic fine particles
      in general solvents have been proposed, and a single-particle layer has been
      formed using such an inorganic solution as a "spreading solution" for an
      interfacial film. Surface modification of ZnO is performed using a long-chain
      carboxylic acid. Accordingly, a regular arrangement of ZnO can be easily achieved
      in order to overcome the relatively weak van der Walls interactions between
      inorganic materials. A condensed Langmuir monolayer of these particles is also
      formed. A multiparticle layered structure is constructed by the Langmuir-Blodgett
      (LB) technique. Out-of-plane XRD measurement results for a single-particle layer
      of organo-ZnO clearly show a sharp peak at 42 A. This peak is attributed to the
      distance between ZnO layers. The AFM image of this single-particle layer of
      organo-ZnO shows a particle assembly with a uniform height of 60 nm. These
      aggregated particles form large two-dimensional crystals. In other words, a
      regular periodic structure along the c-axis and a condensed single-particle layer
      had been fabricated using Langmuir and LB techniques.

PMID- 25978557
TI  - Highly effective removal of basic fuchsin from aqueous solutions by anionic
      polyacrylamide/graphene oxide aerogels.
AB  - Novel anionic polyacrylamide/graphene oxide aerogels were prepared by a freeze
      drying method and used to remove basic fuchsin from aqueous solutions. These
      aerogels were sponge-like solid with lightweight, fluffy and porous structure.
      The batch adsorption experiments were carried out to study the effect of various
      parameters, such as the solution pH, adsorbent dose, contact time and temperature
      on adsorption properties of basic fuchsin onto anionic polyacrylamide/graphene
      oxide aerogels. The kinetics of adsorption corresponded to the pseudo-second
      order kinetic model. The Langmuir adsorption isotherm was suitable to describe
      the equilibrium adsorption process. The maximum adsorption capacity was up to
      1034.3 mg/g, which indicated that anionic polyacrylamide/graphene oxide aerogels
      were promising adsorbents for removing dyes pollutants from aqueous solution.

PMID- 25978558
TI  - High-value utilization of egg shell to synthesize Silver and Gold-Silver core
      shell nanoparticles and their application for the degradation of hazardous dyes
      from aqueous phase-A green approach.
AB  - The common household material, egg shell of Anas platyrhynchos is utilized for
      the synthesis of Silver and Gold-Silver core shell nanoparticles using greener,
      environment friendly and economic way. The egg shell extracts were acting as a
      stabilizing and reducing agents. This method avoids the use of external reducing
      and stabilizing agents, templates and solvents. The effects of various reaction
      parameters, such as reaction temperature, concentration in the formation of
      nanoparticles have also been investigated. The compositional abundance of gelatin
      may be envisaged for the effective reductive as well as stabilizing potency. The
      mechanisms for the formation of NPs have also been presented. The synthesized Ag
      NPs formed were predominantly spherical in nature with an average size of
      particles in the range of 6-26 nm. While, Au-Ag core shell nanoparticles formed
      were spherical and oval shaped, within a narrow size spectrum of 9-18 nm. Both
      the Ag NPs Au-and Ag core shell nanoparticles showed characteristic Bragg's
      reflection planes of fcc structure and surface plasmon resonance at 430 nm and
      365 nm, respectively. The NPs were utilized for the removal of toxic and
      hazardous dyes, such as Rose Bengal, Methyl Violet 6 B and Methylene Blue from
      aqueous phase. Approximately 98.2%, 98.4% and 97% degradations of Rose Bengal,
      Methyl Violet 6 B, and Methylene Blue were observed with Ag NPs, while the
      percentage degradation of these dyes was 97.3%, 97.6% and 96% with Au-Ag NPs,
      respectively. Therefore, the present study has opened up an innovative way for
      synthesizing Ag NPs and Au-Ag bimetallic nanostructures of different morphologies
      and sizes involving the utilization of egg shell extract. The high efficiency of
      the NPs as photocatalysts has opened a promising application for the removal of
      hazardous dyes from the industrial effluents.

PMID- 25978559
TI  - Robotic-Assisted Ureteral Re-implantation: A Case Series.
AB  - INTRODUCTION: Minimally invasive surgical techniques are currently used for
      numerous urologic disorders and generally offer decreased morbidity and
      equivalent outcomes compared with open surgery. There is a relative paucity of
      data on robot-assisted ureteral re-implantation (RAUR) in adult patients for
      benign stricture disease. PATIENTS AND METHODS: We retrospectively reviewed our
      recent experience with mid-/distal ureteral reconstruction at a single tertiary
      care center. From 2010 to 2012, 13 consecutive patients presenting with benign
      obstruction of mid-/distal ureters were managed with RAUR. RESULTS: In all cases
      the operative procedure was undertaken with six-port transperitoneal access, and
      all procedures were completed robotically. All ureters (left, n=5; right, n=7;
      bilateral, n=1) were re-implanted in a standard Bricker fashion into the dome of
      the bladder with (n=8) or without (n=6) a psoas hitch. Catheters were removed 4
      11 days postoperatively, and all cystograms were negative for leak. Stents were
      removed 14-48 days after surgery. All were negative for hydronephrosis. Average
      follow-up was 10 (range, 2-20) months. There were two grade 1, two grade 2, two
      grade 3, and no grade 4 or 5 complications in 3 patients. CONCLUSIONS: RAUR is a
      safe and effective procedure. Extensive laparoscopic lysis of adhesions
      represents the primary challenge to an otherwise straightforward minimally
      invasive surgery. At our institution, RAUR has replaced open ureteral re
      implantation as the preferred treatment for benign mid-/distal ureteral stricture
      disease.

PMID- 25978560
TI  - Mobility of phosphorus induced by sediment resuspension in the Three Gorges
      Reservoir by flume experiment.
AB  - The mobility of phosphorus (P) induced by sediment resuspension have been
      examined in a circulated flume. During the flume run, the water level and
      velocity were monitored, and water samples were taken for measurement of sediment
      and P concentrations. Peak values of both the P and sediment concentrations
      existed at x=4m, and then decreased slightly along the flume due to deposition. A
      faster P release was observed for coarser sediment, while a more sustained P
      release for finer sediment. Combining with the measured data from Yangtze River
      and sorption experiment, the relation between the load of total P (LTP) and
      sediment load (Qs) was estimated, and the expressions of distribution coefficient
      Kd and the concentration of particulate P (PP) were obtained. This study
      established a bridge between the small-scale sorption experiment and the field
      observation of natural scale, providing references for the management of
      contaminated sediment in natural rivers. 

PMID- 25978561
TI  - The Diced Cartilage Glue Graft for Radix Augmentation in Rhinoplasty.

PMID- 25978562
TI  - Social networks and physical activity behaviors among cancer survivors: data from
      the 2005 Health Information National Trends Survey.
AB  - The study examined the relation between social networks and physical activity
      behaviors among cancer survivors. The authors examined 873 cancer survivors (596
      women, 277 men) 50 years of age or older who participated in the 2005 Health
      Information National Trends Survey. Multivariate logistic regression analysis
      showed that survivors who talked about health with friends/family were more
      likely to pay attention to new physical activity recommendations (OR = 2.89, CI
      [1.01, 8.33]). Female survivors were more likely to pay attention to new physical
      activity recommendations (OR = 2.65, CI [1.55, 4.53]) and more likely to have
      seen, heard, or read physical activity/exercise and cancer information within the
      past 12 months (OR = 2.09, CI [1.13, 3.85]) compared with their male
      counterparts. For male survivors, those who were a member of at least one
      community organization were more likely to pay attention to new physical
      activity/exercise recommendations (OR = 5.31, CI [1.32, 21.22]) than the men who
      were not members. Overall, cancer survivors with a social network (i.e., talking
      to family/friends about health) were more likely to pay attention to new exercise
      recommendations compared with those who did not have a social network.
      Significant differences were also observed by gender with physical activity
      levels, knowledge, and attitudes. Social networking is an important component in
      cancer survivorship and further research is needed to encourage social networking
      strategies that might facilitate in increasing physical activity behaviors among
      cancer survivors.

PMID- 25978563
TI  - Spinal circuits for motor learning.
AB  - Studies of motor learning have largely focussed on the cerebellum, and have
      provided key concepts about neural circuits required. However, other parts of the
      nervous system are involved in learning, as demonstrated by the capacity to
      'train' spinal circuits to produce locomotion following spinal cord injury. While
      somatosensory feedback is necessary for spinal motor learning, feed forward
      circuits within the spinal cord must also contribute. In fact, motoneurons
      themselves could act as comparators that integrate feed forward and feedback
      inputs, and thus contribute to motor learning. Application of cerebellar-derived
      principles to spinal circuitry leads to testable predictions of spinal
      organization required for motor learning. 

PMID- 25978565
TI  - Targeting 'types: Precision Medicine in Pulmonary Disease.

PMID- 25978564
TI  - The Novel Gene CRNDE Encodes a Nuclear Peptide (CRNDEP) Which Is Overexpressed in
      Highly Proliferating Tissues.
AB  - CRNDE, recently described as the lncRNA-coding gene, is overexpressed at RNA
      level in human malignancies. Its role in gametogenesis, cellular differentiation
      and pluripotency has been suggested as well. Herein, we aimed to verify our
      hypothesis that the CRNDE gene may encode a protein product, CRNDEP. By using
      bioinformatics methods, we identified the 84-amino acid ORF encoded by one of two
      CRNDE transcripts, previously described by our research team. This ORF was cloned
      into two expression vectors, subsequently utilized in localization studies in
      HeLa cells. We also developed a polyclonal antibody against CRNDEP. Its
      specificity was confirmed in immunohistochemical, cellular localization, Western
      blot and immunoprecipitation experiments, as well as by showing a statistically
      significant decrease of endogenous CRNDEP expression in the cells with transient
      shRNA-mediated knockdown of CRNDE. Endogenous CRNDEP localizes predominantly to
      the nucleus and its expression seems to be elevated in highly proliferating
      tissues, like the parabasal layer of the squamous epithelium, intestinal crypts
      or spermatocytes. After its artificial overexpression in HeLa cells, in a fusion
      with either the EGFP or DsRed Monomer fluorescent tag, CRNDEP seems to stimulate
      the formation of stress granules and localize to them. Although the exact role of
      CRNDEP is unknown, our preliminary results suggest that it may be involved in the
      regulation of the cell proliferation. Possibly, CRNDEP also participates in
      oxygen metabolism, considering our in silico results, and the correlation between
      its enforced overexpression and the formation of stress granules. This is the
      first report showing the existence of a peptide encoded by the CRNDE gene. 

PMID- 25978566
TI  - Muscle weakness in critical illness.

PMID- 25978567
TI  - Understanding the global burden of pediatric sepsis.

PMID- 25978568
TI  - Personalizing medicine. Quantification of cystic fibrosis using computed
      tomography.

PMID- 25978569
TI  - Screening for Lung Cancer Using Low-Dose Computed Tomography. Are We Headed for
      DANTE's Paradise or Inferno?

PMID- 25978570
TI  - IFN-gamma Release Assays for Risk Assessment in Contacts of Patients with
      Tuberculosis in Low-Burden European Countries.

PMID- 25978571
TI  - Toward Resolving the Paradox of the Critical Role of the DosR Regulon in
      Mycobacterium tuberculosis Persistence and Active Disease.

PMID- 25978572
TI  - Chlorhexidine Bathing Impact on Infections, Effect of Etomidate on Sepsis
      Mortality, and Evaluation of Ventilator-associated Conditions.

PMID- 25978573
TI  - Co-occurrence of Pneumoperitoneum and Pneumothorax in a Patient with
      Pleuroparenchymal Fibroelastosis.

PMID- 25978574
TI  - Sustained Benefit of Community-based Tuberculosis Interventions after 30 Years.

PMID- 25978575
TI  - Circulating levels of antioxidant vitamins correlate with better lung function
      and reduced exposure to ambient pollution.

PMID- 25978576
TI  - Reduction of airway smooth muscle mass after bronchial thermoplasty: are we there
      yet?

PMID- 25978577
TI  - Reply: reduction of airway smooth muscle mass by bronchial thermoplasty in
      patients with severe asthma.

PMID- 25978578
TI  - Lung Cancer Screening: The Balance between Harm and Benefit.

PMID- 25978580
TI  - Erratum: Bioactive Lipids in Emphysema: Decoding Fat to Reveal COPD Phenotypes.

PMID- 25978579
TI  - Reply: Lung Cancer Screening: The Balance between Harm and Benefit.

PMID- 25978581
TI  - Erratum: daily rifapentine for treatment of pulmonary tuberculosis: a randomized,
      dose-ranging trial.

PMID- 25978582
TI  - Enhancement of Inducible Nitric Oxide Synthase Activity by Low Molecular Weight
      Peptides Derived from Protamine: A Potential Therapy for Chronic Rhinosinusitis.
AB  - Nitric oxide (NO) is a key immune defense agent that is produced from l-arginine
      in the airways by leukocytes and airway epithelial cells, primarily via inducible
      nitric oxide synthase (iNOS). Deficiencies in nasal NO levels have been
      associated with diseases such as primary ciliary dyskinesia and chronic
      rhinosinusitis. Herein, we demonstrate a proof-of-concept regarding a potential
      new therapeutic approach for such disorders. We show that arginine-rich low
      molecular weight peptides (LMWPs) derived from the FDA-approved protamine
      (obtained from salmon sperm) are effective at significantly raising NO production
      in both RAW 264.7 mouse macrophage and LA4 mouse epithelial cell lines. LMWP is
      produced using a stable, easily produced immobilized thermolysin gel column
      followed by size-exclusion purification. Monomeric l-arginine induces
      concentration-dependent increases in NO production in stimulated RAW 264.7 and
      LA4 cells, as measured by stable nitrite in the cell media. In stimulated RAW
      264.7 cells, LMWP significantly increases iNOS expression and total NO production
      12-24 h post-treatment compared to cells given equivalent levels of monomeric l
      arginine. For stimulated LA4 cells, LMWPs are effective in significantly
      increasing NO production compared to equivalent l-arginine monomer concentrations
      over 24 h but do not substantially enhance iNOS expression. The use of the
      arginase inhibitor S-boronoethyl-l-cysteine in combination with LMWPs results in
      even higher NO production by stimulated RAW 264.7 cells and LA4 cells. Increases
      in NO due to LMWPs, compared to l-arginine, occur only after 4 h, which may be
      due to iNOS elevation rather than increased substrate availability. 

PMID- 25978583
TI  - Removal of lead and phosphate ions from aqueous solutions by organo-smectite.
AB  - Smectite has been modified using hexadecyltrimethyl ammonium bromide in an amount
      of double cationic exchange capacity. This alteration makes it possible to use
      organo-smectite as a sorbent to remove anionic forms. The experiment consisted of
      the interchangeable sorption of phosphate(V) and lead(II) by organo-smectite.
      Research was carried out with varying pH (2-5) and various concentrations (0.1-5
      mmol/L). Organo-smectite with previously adsorbed lead ions removed more
      phosphate than the untreated organo-smectite. Experimental data show that lead is
      more likely to absorb on the organo-smectite than on the organo-smectite with
      previously adsorbed phosphate ions. It follows that the most effective use of the
      organo-smectite is through the sorption of first - Pb cations and then PO4
      anions. With an increasing concentration of Pb(II) or P(V), the sorption
      efficiency increases. The maximum sorption efficiency of lead and phosphate ions
      is observed at pH 5. This enables the removal of harmful lead and phosphorus
      compounds from waste water and immobilizes them on the sorbent's surface. The
      alternating reactions of lead and phosphorus ions result in the crystallization
      of brompyromorphite Pb5(PO4)3Br. 

PMID- 25978584
TI  - Oxidation of methane by an N-bridged high-valent diiron-oxo species: electronic
      structure implications on the reactivity.
AB  - High-valent iron-oxo species are key intermediates in C-H bond activation of
      several substrates including alkanes. The biomimic heme and non-heme mononuclear
      Fe(IV)=O complexes are very popular in this area and have been thoroughly studied
      over the years. These species despite possessing aggressive catalytic ability,
      cannot easily activate inert C-H bonds such as those of methane. In this context
      dinuclear complexes have gained attention, particularly MU-nitrido dinuclear iron
      species [(TPP)(m-CBA)Fe(IV)(MU-N)Fe(IV)(O)(TPP(+))](-) reported lately exhibits
      remarkable catalytic abilities towards substrates such as methane. Here using DFT
      methods, we have explored the electronic structure and complex spin-state
      energetics present in this species. To gain insights into the nature of bonding,
      we have computed the absorption, the EPR and the Mossbauer parameters and have
      probed the mechanism of methane oxidation by the dinuclear Fe(IV)=O species.
      Calculated results are in agreement with the experimental data and our
      calculations predict that in [(TPP)(m-CBA)Fe(IV)(MU-N)Fe(IV)(O)(TPP(+))](
      )species, the two high-spin iron centres are antiferromagnetically coupled
      leading to a doublet ground state. Our calculations estimate an extremely low
      kinetic barrier of 26.6 kJ mol(-1) (at doublet surface) for the C-H bond
      activation of methane by the dinuclear Fe(IV)=O species. Besides these
      mechanistic studies on the methane activation reveal the unique electronic
      cooperativity present in this type of dinuclear complex and unravel the key
      question of why mononuclear analogues are unable to perform such reactions.

PMID- 25978586
TI  - Erratum.

PMID- 25978587
TI  - Correction to In Situ Determination of Colloidal Gold Concentrations with UV-Vis
      Spectroscopy: Limitations and Perspectives.

PMID- 25978585
TI  - Systematic review of catheter-based intra-arterial therapies in hepatocellular
      carcinoma: state of the art and future directions.
AB  - Intra-arterial therapies (IATs) play a pivotal role in the management of patients
      with primary and secondary liver malignancies. The unique advantages of these
      treatments are their ability to selectively deliver a high dose of anticancer
      treatment while preserving healthy liver tissue. The proven efficacy of these
      catheter-based locoregional therapies in a highly systemic chemoresistant cancer
      such as hepatocellular carcinoma (HCC), along with the minimally invasive nature
      of these treatments, quickly yielded wide acceptance in the medical community and
      revolutionized the field of Interventional Oncology. In this article, we describe
      the clinical rationale and background of catheter-based IATs. We provide an
      overview of clinical achievements of these treatments alone and in combination
      with sorafenib in patients with HCC. 

PMID- 25978588
TI  - Phosphine-iminopyridines as platforms for catalytic hydrofunctionalization of
      alkenes.
AB  - A series of phosphine-diimine ligands were synthesized by the condensation of 2
      (diphenylphosphino)aniline (PNH2) with a variety of formyl and ketopyridines.
      Condensation of PNH2 with acetyl- and benzoylpyridine yielded the
      Ph2P(C6H4)N?C(R)(C5H4N), respectively abbreviated PN(Me)py and PN(Ph)py. With
      ferrous halides, PN(Ph)py gave the complexes FeX2(PN(Ph)py) (X = Cl, Br).
      Condensation of pyridine carboxaldehyde and its 6-methyl derivatives with PNH2
      was achieved using a ferrous template, affording low-spin complexes
      [Fe(PN(H)py(R))2](2+) (R = H, Me). Dicarbonyls Fe(PN(R)py)(CO)2 were produced by
      treating PN(Me)py with Fe(benzylideneacetone)(CO)3 and reduction of
      FeX2(PN(Ph)py) with NaBEt3H under a CO atmosphere. Cyclic voltammetric studies
      show that the [FeL3(CO)2](0/-) and [FeL3(CO)2](+/0) couples are similar for a
      range of tridentate ligands, but the PN(Ph)py system uniquely sustains two one
      electron reductions. Treatment of Fe(PN(Ph)py)X2 with NaBEt3H gave active
      catalysts for the hydroboration of 1-octene with pinacolborane. Similarly, these
      catalysts proved active for the addition of diphenylsilane, but not
      HSiMe(OSiMe3)2, to 1-octene and vinylsilanes. Evidence is presented that
      catalysis occurs via iron hydride complexes of intact PN(Ph)py. 

PMID- 25978589
TI  - Hyperperfusion in carotid stenting patients.
AB  - PURPOSE: This study aimed to define hyperperfusion in carotid stenting patients
      without excluding patients with stenosis on the contralateral side. MATERIALS AND
      METHODS: A total of 32 patients were enrolled. Prestent computed tomography
      perfusions were performed within 1 week before stenting, poststent perfusions 3
      days after stenting. Prestent relative cerebral blood volume, relative cerebral
      blood flow, and relative mean transient time (rMTT) were calculated by dividing
      measurements from ipsilateral stent sides to contralateral sides and prestent
      difference mean transit time (dMTT) by subtracting contralateral mean transient
      time (MTT) from ipsilateral MTT. Poststent values were calculated similarly. For
      differences between prestent and poststent values, independent t test was used
      between groups and paired sample t test within the groups. RESULTS: Of the 31
      patients, 4 showed poststent clinical hyperperfusion syndrome. Six showed
      poststent radiologic hyperperfusion with increased cerebral blood flow, increased
      or spared cerebral blood volume, and shortened MTT values, but only 1
      demonstrated clinical hyperperfusion. Between normal and hyperperfused groups,
      only appreciable difference was noted in prestent and poststent dMTT without
      statistical significance. Within the groups, only statistical difference (P <
      0.001) was noted in rMTT and dMTT in normal groups and no significant difference
      in the hyperperfused group. CONCLUSIONS: Radiologic hyperperfusion does not match
      clinical hyperperfusion. Normal group responded to stenting with statistically
      significant changes of rMTT and dMTT. Hyperperfusion mostly occurred in the
      contralateral critically stenosed patients. The hyperperfused group, due to
      similar MTT of both hemispheres and ipsilateral internal carotid artery being the
      main feeder of both hemispheres, did not show significant changes in their rMTT
      and dMTT values after stenting. This shows that reduced hemodynamic reserve is
      the main reason behind the hyperperfusion after carotid stenting.

PMID- 25978590
TI  - Feasibility of 3-dimensional sampling perfection with application optimized
      contrast sequence in the evaluation of patients with hydrocephalus.
AB  - PURPOSE: This study aimed to investigate the effectiveness and additive value of
      T2W 3-dimensional sampling perfection with application optimized contrast (3D
      SPACE) with variant flip-angle mode in imaging of all types of hydrocephalus. Our
      secondary objective was to assess the reliability of 3D-SPACE sequence and
      correspondence of the results with phase-contrast magnetic resonance imaging (PC
      MRI)-based data. MATERIALS AND METHODS: Forty-one patients with hydrocephalus
      have undergone 3-T MRI. T2W 3D-SPACE sequence has been obtained in addition to
      routine hydrocephalus protocol. Cerebrospinal fluid circulation,
      presence/type/etiology of hydrocephalus, obstruction level scores, and diagnostic
      levels of confidence were evaluated separately by 2 radiologists. In the first
      session, routine sequences with PC-MRI were evaluated, and in another session,
      only 3D-SPACE and 3-dimensional magnetization prepared rapid acquisition gradient
      echo sequences were evaluated. Results obtained in these sessions were compared
      with each other and those obtained in consensus session. RESULTS: Agreement
      values were very good for both 3D-SPACE and PC-MRI sequences (P < 0.001 for all).
      Also, the correlation of more experienced reader's 3D-SPACE-based scores and
      consensus-based scores was perfect (kappa = 1, P < 0.001).The mean value of PC
      MRI-based confidence scores were lower than those obtained in 3D-SPACE and
      consensus sessions. CONCLUSIONS: T2W 3D-SPACE sequence provides morphologic
      cerebrospinal fluid flow data. It is a noninvasive technique providing extensive
      multiplanar reformatted images with a lower specific absorption rate. These
      advantages over PC-MRI make 3D-SPACE sequence a promising tool in management of
      patients with hydrocephalus.

PMID- 25978591
TI  - Three-Tesla imaging of the pituitary and parasellar region: T1-weighted 3
      dimensional fast spin echo cube outperforms conventional 2-dimensional magnetic
      resonance imaging.
AB  - OBJECTIVE: We explored how a novel T1-weighted 3-dimensional (3D) fast spin echo
      (FSE) sequence (Cube; GE, Waukesha, Wis) might outperform conventional 2
      dimensional (2D) FSE techniques for contrast-enhanced imaging of the pituitary
      and parasellar region. METHODS: Ninety-one patients were imaged with 3D Cube and
      conventional 2D FSE on a 3.0-T magnetic resonance scanner. Two neuroradiologists
      independently assessed images for anatomical delineation (infundibulum, optic
      apparatus, and cavernous sinus), degree of artifact, and confidence in lesion
      definition or exclusion using a 5-point scale. In addition, the readers were
      asked to rank overall preference. RESULTS: Readers A and B found 3D Cube to be
      better or equal to 2D FSE in 84% and 86% of the cases. Three-dimensional Cube
      provided significantly better images than 2D FSE with respect to delineation of
      the infundibulum (P < 0.0001), cavernous sinus (P < 0.0001), optic apparatus (P =
      0.002 for reader A and P = 0.265 for reader B), and fewer artifacts at the sellar
      floor (P < 0.0001). Three-dimensional Cube provided greater lesion conspicuity or
      confidence in lesion exclusion (P < 0.0001). CONCLUSIONS: Three-dimensional Cube
      provides superior quality with thinner slices as well as diminished artifact and
      can replace conventional 2D FSE sequences for routine evaluations of the
      pituitary and parasellar region.

PMID- 25978592
TI  - Primary ovarian endometrioid adenocarcinoma: magnetic resonance imaging findings
      including a preliminary observation on diffusion-weighted imaging.
AB  - OBJECTIVE: This study aimed to investigate the magnetic resonance imaging (MRI)
      features of ovarian endometrioid adenocarcinoma (OEC) and to evaluate
      conventional MRI and diffusion-weighted imaging (DWI) for diagnosing OEC.
      MATERIALS AND METHODS: Twenty patients with OEC proven by surgery and pathology
      underwent MRI. The MRI features of the tumors evaluated included laterality,
      shape, size, configuration, mural nodules, signal intensity, apparent diffusion
      coefficient (ADC) values, enhancement, peritoneal implants, ascites, and
      synchronous primary cancer (SPC) of the ovary and endometrium. RESULTS:
      Unilateral ovarian masses were observed in 18 (90%) of the 20 patients with 22
      OEC lesions, whereas the remaining 2 (10%) patients had bilateral masses. Oval,
      lobulated, and irregular shapes were observed in 13 (59%), 6 (27%), and 3 (14%)
      tumors, respectively. The maximum diameter of the tumors ranged from 3.7 to 22.5
      cm, with a mean of 11.2 +/- 5.1 cm. Fifteen (68%) masses were mainly cystic with
      mural nodules, 5 (23%) were mixed cystic-solid, and 2 (9%) were solid. The solid
      components of tumors showed isointensity (100%) on T1-weighted imaging (T1WI),
      heterogeneous hyperintensity on T2-weighted imaging (T2WI) (86%), and
      hyperintensity on DWI (82%), with a mean ADC value of (0.96 +/- 0.20) * 10 mm/s.
      The cystic components showed isointensity or hyperintensity (85%) on T1WI,
      hyperintensity on T2WI (100%), and hypointensity on DWI (63%), with a mean ADC
      value of (2.27 +/- 0.27) * 10 mm/s. Ten (50%) of the patients were SPC. The mean
      ADC values of the solid components were (0.85 +/- 0.19) * 10 mm/s and (1.08 +/-
      0.15) * 10 mm/s in only-OEC and SPC, respectively, with a statistically
      significant difference (P = 0.012). CONCLUSIONS: Ovarian endometrioid
      adenocarcinoma usually appears as a large, oval, or lobulated cystic mass with
      mural nodules. Cystic components show isointensity or hyperintensity on T1WI,
      solid components and hyperintensity on T2WI and DWI. Synchronous primary cancer
      of the ovary endometrium is another characteristic feature of OEC.

PMID- 25978594
TI  - Molecular Donor-Bridge-Acceptor Strategies for High-Capacitance Organic
      Dielectric Materials.
AB  - Donor-bridge-acceptor (DBA) systems occupy a rich history in molecular
      electronics and photonics. A key property of DBA materials is their typically
      large and tunable (hyper)polarizabilities. While traditionally, classical
      descriptions such as the Clausius-Mossotti formalism have been used to relate
      molecular polarizabilities to bulk dielectric response, recent work has shown
      that these classical equations are inadequate for numerous materials classes.
      Creating high-dielectric organic materials is critically important for utilizing
      unconventional semiconductors in electronic circuitry. Employing a plane-wave
      density functional theory formalism, we investigate the dielectric response of
      highly polarizable DBA molecule-based thin films. Such films are found to have
      large dielectric response arising from cooperative effects between donor and
      acceptor units when mediated by a conjugated bridge. Moreover, the dielectric
      response can be systematically tuned by altering the building block donor,
      acceptor, or bridge structures and is found to be nonlinearly dependent on
      electric field strength. The computed dielectric constants are largely
      independent of the density functional employed, and qualitative trends are
      readily evident. Remarkably large computed dielectric constants >15.0 and
      capacitances >6.0 MUF/cm(2) are achieved for squaraine monolayers, significantly
      higher than in traditional organic dielectrics. Such calculations should provide
      a guide for designing high-capacitance organic dielectrics that should greatly
      enhance transistor performance. 

PMID- 25978593
TI  - Velocity quantification by electrocardiography-gated phase contrast magnetic
      resonance imaging in patients with cardiac arrhythmia: a simulation study based
      on real time transesophageal echocardiography data in atrial fibrillation.
AB  - OBJECTIVE: To systematically investigate the impact of beat-to-beat variations on
      electrocardiography (ECG)-gated multibeat flow imaging with phase contrast (PC)
      magnetic resonance imaging (MRI) based on real time in vivo transesophageal
      echocardiography (TEE) data in patients with known arrhythmia. METHODS: Real-time
      2-dimensional Doppler TEE was performed in five patients with atrial fibrillation
      (4 men, age = 64 +/- 8.7 years). The TEE data provided real-time left atrial (LA)
      and left ventricular (LV) flow velocities in consecutive cardiac cycles with
      different RR interval durations. The PC MRI acquisitions were simulated from the
      TEE velocity measures by constructing time-resolved k-space data for segmented
      sampling schemes typically used for ECG-gated 2-dimensional PC MRI. Each
      simulation was repeated 100 times to minimize effects from data that may be
      weighted to a particular beat in the center of k-space. The resulting LA and LV
      velocities were compared to the average TEE velocities and data from individual
      cardiac cycles. RESULTS: Despite beat-to-beat variations of velocities in TEE
      data, ECG-gated flow imaging with MRI could reproduce persistent average LA and
      LV mean velocities within 7.0% to 7.4% compared to TEE. CONCLUSIONS: The PC MRI
      velocity measurements in patients with varying RR interval durations are not
      significantly different from time-averaged real-time velocity data for a typical
      segmented k-space data acquisition schemes. Though beat-to-beat variations in
      atrial velocities that were observed with TEE cannot be detected with ECG-gated
      multibeat PC MRI, it can reliably assess average flow patterns across multiple
      beats.

PMID- 25978595
TI  - Liquiritigenin Potentiates the Inhibitory Effects of Cisplatin on Invasion and
      Metastasis Via Downregulation MMP-2/9 and PI3 K/AKT Signaling Pathway in B16F10
      Melanoma Cells and Mice Model.
AB  - Liquiritigenin (LQ) is a flavanone extracted from glycyrrhizae. Previous studies
      have demonstrated that LQ possesses antimigration properties in HELA and A549
      cells. The present research, as an extension of our earlier ones, investigated
      whether LQ can enhance the antimigration and antiinvasion effect of cis-diamine
      dichloroplatinum (CDDP) in B16F10 melanoma cell. The data indicated that LQ (25,
      50, 100, 200 MUM) combined with CDDP (2 MUM) significantly reduced B16F10 cell
      viability compared to CDDP (2 MUM)-treated only. The different doses of LQ
      combined with CDDP significantly suppressed cell migration (21.5%, 49.6%, 75.6%)
      and cell invasion (26.2%, 51.4%, 69.5%) compared with CDDP-treated alone,
      suggesting that LQ enhance the inhibition action of CDDP on cell migration and
      invasion. Moreover, LQ/CDDP combination led to the downregulation of protein
      expression of MMP-2/9, PI3 K, p-AKT, and upregulated PTEN protein level that play
      an important role in tumor metastasis progression. Further study demonstrated the
      enhancement effect of LQ on CDDP suppressing lung metastasis in a mice model
      being inoculated by the B16F10 melanoma cells. In conclusion, the results
      suggested that LQ plays an intensive role on CDDP suppressing invasion and
      metastasis through regulating the PI3 K/AKT signal pathway and suppressing the
      protein expression of MMP-2/9. 

PMID- 25978596
TI  - Isofuranodiene, the main volatile constituent of wild celery (Smyrnium olusatrum
      L.), protects d-galactosamin/lipopolysacchride-induced liver injury in rats.
AB  - Isofuranodiene is a natural sesquiterpene rich occurring in Smyrnium olusatrum, a
      forgotten culinary herb which was marginalised after the domestication of the
      improved form of celery. Our recent data showed that isofuranodiene inhibited the
      proliferation and induced apoptosis in cancer cells. In this study, we
      investigated its protective effect on d-galactosamine/lipopolysacchride
      (GalN/LPS)-induced liver injury in SD rats. Oral administration of isofuranodiene
      (20 and 50 mg/kg) dramatically inhibited GalN/LPS-induced serum elevation of
      aspartate aminotransferase, alanine aminotransferase and malondialdehyde levels,
      and significantly ameliorated liver injury as evidenced by the histological
      improvement in H&E staining. Furthermore, isofuranodiene treatment significantly
      inhibited GalN/LPS-induced mRNA expression of IL-1beta, IL-6 and inducible nitric
      oxide synthase in liver tissues. The results from this study showed that
      isofuranodiene protects GalN/LPS-induced liver injury in SD rats and suggested
      that it may be a potential functional food ingredient for the prevention and
      treatment of liver diseases.

PMID- 25978597
TI  - Vitamin D deficiency and energy metabolism.

PMID- 25978598
TI  - SIRT1 in the Ventromedial Hypothalamus: A Nutrient Sensor Input Into the Internal
      Timekeeper.

PMID- 25978599
TI  - A direct role for thyroid hormone in development of the adrenal cortex.

PMID- 25978602
TI  - Systems biology approach reveals possible evolutionarily conserved moonlighting
      functions for enolase.
AB  - Glycolytic enzymes, such as enolase, have been described as multifunctional
      complex proteins that also display non-glycolytic activities, termed moonlighting
      functions. Although enolase multifunctionality has been described for several
      organisms, the conservation of enolase alternative functions through different
      phyla has not been explored with more details. A useful strategy to investigate
      moonlighting functions is the use of systems biology tools, which allow the
      prediction of protein functions/interactions by graph design and analysis. In
      this work, available information from protein-protein interaction (PPI) databases
      were used to design enolase PPI networks for four eukaryotic organisms, namely
      Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces
      cerevisiae, covering a wide spectrum of this domain of life. PPI networks with
      number of nodes ranging from 140 to 411 and up to 15,855 connections were
      generated, and modularity and centrality analyses, and functional enrichment were
      performed for all of them. The performed analyses showed that enolase is a
      central node within the networks, and that, in addition to its canonical
      interactions with proteins related to glycolysis and energetic metabolism, it is
      also part of protein clusters related to different biological processes, like
      transcription, development, and apoptosis, among others. Some of these non
      glycolytic clusters, are partially conserved between networks, in terms of
      overall sharing of orthologs, overall cluster structure, and/or at the levels of
      key regulatory proteins within clusters. Overall, our results provided evidences
      of enolase multifunctionality and evolutionary conservation of enolase PPIs at
      all these levels. 

PMID- 25978603
TI  - DJ-1-mediated upregulation of serine palmitoyltransferase 2 controls vascular
      neointima via S1P autocrine.

PMID- 25978605
TI  - Paradoxical coronary embolism as a cause of non-atherosclerotic acute coronary
      syndrome.

PMID- 25978604
TI  - Incidence, predictors and outcomes of immediate decrease in thrombolysis in
      myocardial infarction flow immediately after paclitaxel-coated balloon
      angioplasty.

PMID- 25978606
TI  - Klotho protein: A potential therapeutic agent during myocardial ischemia and
      reperfusion.

PMID- 25978607
TI  - Elevated high-sensitive cardiac troponin T levels are associated with low
      skeletal muscle mass in abdominal surgical oncology patients at risk for coronary
      artery disease.

PMID- 25978608
TI  - Contrast media induced myocardial infarction in patient with subtotal LAD
      occlusion.

PMID- 25978609
TI  - Self limitation of coronary pseudoaneurysm after transluminal coronary rotational
      atherectomy.

PMID- 25978610
TI  - Compression of superior caval vein - New clinical problem of aortopathy.

PMID- 25978611
TI  - Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian
      agenda.
AB  - Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs
      a considerable burden of stroke and associated healthcare costs. Asians have AF
      risk factors similar to Caucasians and a similarly increased risk of AF-related
      stroke; however, with a vast and rapidly ageing population, Asia bears a
      disproportionately large disease burden. Urgent action is warranted to avert this
      potential health crisis. Antithrombotic therapy with oral anticoagulants is the
      most effective means of preventing stroke in AF and is a particular priority in
      Asia given the increasing disease burden. However, AF in Asia remains
      undertreated. Conventional oral anticoagulation with warfarin is problematic in
      Asia due to suboptimal control and a propensity among Asians to warfarin-induced
      intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage,
      there are considerable gaps between AF treatment guidelines and clinical practice
      in Asia, in particular overuse of antiplatelet agents and underuse of
      anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor
      Xa inhibitors are non-inferior in preventing stroke and significantly reduce the
      risk of life-threatening bleeding, particularly intracranial bleeding. These
      agents may therefore provide an appropriate alternative to warfarin in Asian
      patients. There is considerable scope to improve stroke prevention in AF in Asia.
      Key priorities include: early detection of AF and identification of asymptomatic
      patients; assessment of stroke and bleeding risk for all AF patients; evidence
      based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K
      antagonists for AF patients at risk of stroke; controlling hypertension; and
      awareness-raising, education and outreach among both physicians and patients. 

PMID- 25978612
TI  - Myocarditis changes in the stunned myocardial segments in takotsubo syndrome: The
      role of the pattern of ventricular wall motion abnormality.

PMID- 25978613
TI  - Tandem Native Mass-Spectrometry on Antibody-Drug Conjugates and Submillion Da
      Antibody-Antigen Protein Assemblies on an Orbitrap EMR Equipped with a High-Mass
      Quadrupole Mass Selector.
AB  - Native mass spectrometry is emerging as a powerful tool for the characterization
      of intact antibodies and antibody-based therapeutics. Here, we demonstrate new
      possibilities provided by the implementation of a high mass quadrupole mass
      selector on the recently introduced Orbitrap Exactive EMR mass spectrometer. This
      configuration allows precursor ion selection, and thus tandem mass spectrometry
      experiments, even on analytes with masses in the hundreds of kilodaltons. We
      apply tandem mass spectrometry to localize the drug molecules in the therapeutic
      antibody-drug conjugate brentuximab vedotin, which displays a heterogeneous drug
      load. Our tandem MS data reveal that drug conjugation takes place
      nonhomogeneously to cysteine residues both on the light and heavy chains. Next,
      we analyzed how many antigens bind to IgG hexamers, based on a recently described
      antibody mutant IgG1-RGY that forms hexamers and activates complement in
      solution. The fully saturated IgG1-RGY-antigen complexes displayed a
      stoichiometry of IgG:CD38 of 6:12, possessing a molecular weight of about 1.26
      MDa and demonstrating that IgG assembly does not hamper antigen binding. Through
      tandem MS experiments, we retrieve information about the spatial arrangement and
      stoichiometry of the subunits within this complex. These examples underscore the
      potential of this further modified Orbitrap-EMR instrument especially for the in
      depth characterization by native tandem mass spectrometry of antibodies and
      antibody-based constructs. 

PMID- 25978615
TI  - Benzothiadiazole Derivatives as Fluorescence Imaging Probes: Beyond Classical
      Scaffolds.
AB  - This Account describes the origins, features, importance, and trends of the use
      of fluorescent small-molecule 2,1,3-benzothiadiazole (BTD) derivatives as a new
      class of bioprobes applied to bioimaging analyses of several (live and fixed)
      cell types. BTDs have been successfully used as probes for a plethora of
      biological analyses for only a few years, and the impressive responses obtained
      by using this important class of heterocycle are fostering the development of new
      fluorescent BTDs and expanding the biological applications of such derivatives.
      The first use of a fluorescent small-molecule BTD derivative as a selective
      cellular probe dates back to 2010, and since then impressive advances have been
      described by us and others. The well-known limitations of classical scaffolds
      urged the development of new classes of bioprobes. Although great developments
      have been achieved by using classical scaffolds such as coumarins, BODIPYs,
      fluoresceins, rhodamines, cyanines, and phenoxazines, there is still much to be
      done, and BTDs aim to succeed where these dyes have shown their limitations.
      Important organelles and cell components such as nuclear DNA, mitochondria, lipid
      droplets, and others have already been successfully labeled by fluorescent small
      molecule BTD derivatives. New technological systems that use BTDs as the
      fluorophores for bioimaging experiments have been described in recent scientific
      literature. The successful application of BTDs as selective bioprobes has led
      some groups to explore their potential for use in studying membrane pores or
      tumor cells under hypoxic conditions. Finally, BTDs have also been used as
      fluorescent tags to investigate the action mechanism of some antitumor compounds.
      The attractive photophysical data typically observed for pi-extended BTD
      derivatives is fostering interest in the use of this new class of bioprobes.
      Large Stokes shifts, large molar extinction coefficients, high quantum yields,
      high stability when stored in solution or as pure solids, no fading even after
      long periods of irradiation, bright emissions with no blinking, good signal-to
      noise ratios, efficiency to transpose the cell membrane, and irradiation
      preferentially in the visible-light region are just some features noted by using
      BTDs. As the pioneering group in the use of fluorescent small-molecule BTDs for
      bioimaging purposes, we feel pleased to share our experience, results, advances,
      and personal perspectives with the readers of this Account. The readers will
      clearly note the huge advantages of using fluorescent BTDs over classical
      scaffolds, and hopefully they will be inspired and motivated to further BTD
      technology in the fields of molecular and cellular biology. 

PMID- 25978614
TI  - The intestinal barrier in irritable bowel syndrome: subtype-specific effects of
      the systemic compartment in an in vitro model.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a disorder with multifactorial
      pathophysiology. Intestinal barrier may be altered, especially in diarrhea
      predominant IBS (IBS-D). Several mediators may contribute to increased intestinal
      permeability in IBS. AIM: We aimed to assess effects of tryptase and LPS on in
      vitro permeability using a 3-dimensional cell model after basolateral cell
      exposure. Furthermore, we assessed the extent to which these mediators in IBS
      plasma play a role in intestinal barrier function. MATERIALS AND METHODS: Caco-2
      cells were grown in extracellular matrix to develop into polarized spheroids and
      were exposed to tryptase (10 - 50 mU), LPS (1 - 50 ng/mL) and two-fold diluted
      plasma samples of 7 patients with IBS-D, 7 with constipation-predominant IBS (IBS
      C) and 7 healthy controls (HC). Barrier function was assessed by the flux of FITC
      dextran (FD4) using live cell imaging. Furthermore, plasma tryptase and LPS were
      determined. RESULTS: Tryptase (20 and 50 mU) and LPS (6.25 - 50 ng/mL)
      significantly increased Caco-2 permeability versus control (all P< 0.05). Plasma
      of IBS-D only showed significantly elevated median tryptase concentrations (7.1
      [3.9 - 11.0] vs. 4.2 [2.2 - 7.0] vs. 4.2 [2.5 - 5.9] MUg/mL; P<0.05) and LPS
      concentrations (3.65 [3.00 - 6.10] vs. 3.10 [2.60-3.80] vs. 2.65 [2.40 - 3.40]
      EU/ml; P< 0.05) vs. IBS-C and HC. Also, plasma of IBS-D increased Caco-2
      permeability versus HC (0.14450 +/- 0.00472 vs. 0.00021 +/- 0.00003; P < 0.001),
      which was attenuated by selective inhibition of tryptase and LPS (P< 0.05).
      CONCLUSION: Basolateral exposure of spheroids to plasma of IBS-D patients
      resulted in a significantly increased FD4 permeation, which was partially
      abolished by selective inhibition of tryptase and LPS. These findings point to a
      role of systemic tryptase and LPS in the epithelial barrier alterations observed
      in patients with IBS-D.

PMID- 25978616
TI  - Wild type mesenchymal cells contribute to the lung pathology of
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease leading to lungs cysts and
      progressive respiratory failure. Cells of unknown origin accumulate in the lungs
      forming nodules and eventually resulting in lung cysts. These LAM cells are
      described as clonal with bi-allelic mutations in TSC-2 resulting in constitutive
      mTOR activation. However LAM nodules are heterogeneous structures containing
      cells of different phenotypes; we investigated whether recruited wild type cells
      were also present alongside mutation bearing cells. Cells were isolated from LAM
      lung tissue, cultured and characterised using microscopy, immunocytochemistry and
      western blotting. Fibroblast-like cells were identified in lung tissue using
      immunohistochemical markers. Fibroblast chemotaxis toward LAM cells was examined
      using migration assays and 3D cell culture. Fibroblast-like cells were obtained
      from LAM lungs: these cells had fibroblast-like morphology, actin stress fibres,
      full length tuberin protein and suppressible ribosomal protein S6 activity
      suggesting functional TSC-1/2 protein. Fibroblast Activation Protein, Fibroblast
      Specific Protein/S100A4 and Fibroblast Surface Protein all stained subsets of
      cells within LAM nodules from multiple donors. In a mouse model of LAM, tuberin
      positive host derived cells were also present within lung nodules of xenografted
      TSC-2 null cells. In vitro, LAM 621-101 cells and fibroblasts formed spontaneous
      aggregates over three days in 3D co-cultures. Fibroblast chemotaxis was enhanced
      two fold by LAM 621-101 conditioned medium (p=0.05), which was partially
      dependent upon LAM cell derived CXCL12. Further, LAM cell conditioned medium also
      halved fibroblast apoptosis under serum free conditions (p=0.03). Our findings
      suggest that LAM nodules contain a significant population of fibroblast-like
      cells. Analogous to cancer associated fibroblasts, these cells may provide a
      permissive environment for LAM cell growth and contribute to the lung pathology
      of LAM lung disease. 

PMID- 25978618
TI  - Hydrogen gas sensor based on metal oxide nanoparticles decorated graphene
      transistor.
AB  - In this work, in order to enhance the performance of graphene gas sensors,
      graphene and metal oxide nanoparticles (NPs) are combined to be utilized for high
      selectivity and fast response gas detection. Whether at the relatively optimal
      temperature or even room temperature, our gas sensors based on graphene
      transistors, decorated with SnO2 NPs, exhibit fast response and short recovery
      times (~1 seconds) at 50  degrees C when the hydrogen concentration is 100 ppm.
      Specifically, X-ray photoelectron spectroscopy and conductive atomic force
      microscopy are employed to explore the interface properties between graphene and
      SnO2 NPs. Through the complimentary characterization, a mechanism based on charge
      transfer and band alignment is elucidated to explain the physical originality of
      these graphene gas sensors: high carrier mobility of graphene and small energy
      barrier between graphene and SnO2 NPs have ensured a fast response and a high
      sensitivity and selectivity of the devices. Generally, these gas sensors will
      facilitate the rapid development of next-generation hydrogen gas detection. 

PMID- 25978617
TI  - Ambient Air Pollution and Newborn Size and Adiposity at Birth: Differences by
      Maternal Ethnicity (the Born in Bradford Study Cohort).
AB  - BACKGROUND: Exposure to ambient air pollution has been associated with reduced
      size of newborns; however, the modifying effect of maternal ethnicity remains
      little explored among South Asians. OBJECTIVES: We investigated ethnic
      differences in the association between ambient air pollution and newborn's size.
      METHOD: Pregnant women were recruited between 2007 and 2010 for the Born in
      Bradford cohort study, in England. Exposures to particulate matter (<= 10 MUm,
      PM10; <= 2.5 MUm, PM2.5), PM2.5 absorbance, and nitrogen oxides (NOx, NO2) were
      estimated using land-use regressions models. Using multivariate linear regression
      models, we evaluated effect modification by maternal ethnicity ("white British"
      or "Pakistani origin," self-reported) on the associations of air pollution and
      birth weight, head circumference, and triceps and subscapular skinfold thickness.
      RESULTS: A 5-MUg/m3 increase in mean third trimester PM2.5 was associated with
      significantly lower birth weight and smaller head circumference in children of
      white British mothers (-43 g; 95% CI: -76, -10 and -0.28 cm; 95% CI: -0.39, 
      0.17, respectively), but not in children of Pakistani origin (9 g; 95% CI: -17,
      35 and -0.08 cm; 95% CI: -0.17, 0.01, respectively) (p(int) = 0.03 and < 0.001).
      In contrast, PM2.5 was associated with significantly larger triceps and
      subscapular skinfold thicknesses in children of Pakistani origin (0.17 mm; 95%
      CI: 0.08, 0.25 and 0.21 mm; 95% CI: 0.12, 0.29, respectively), but not in white
      British children (-0.02 mm; 95% CI: -0.14, 0.01 and 0.06 mm; 95% CI: -0.06, 0.18,
      respectively) (p(int) = 0.06 and 0.11). Patterns of associations for PM10 and
      PM2.5 absorbance according to ethnicity were similar to those for PM2.5, but
      associations of the outcomes with NO2 and NOx were mostly nonsignificant in both
      ethnic groups. CONCLUSIONS: Our results suggest that associations of ambient PM
      exposures with newborn size and adiposity differ between white British and
      Pakistani origin infants. CITATION: Schembari A, de Hoogh K, Pedersen M, Dadvand
      P, Martinez D, Hoek G, Petherick ES, Wright J, Nieuwenhuijsen MJ. 2015. Ambient
      air pollution and newborn size and adiposity at birth: differences by maternal
      ethnicity (the Born in Bradford study cohort). Environ Health Perspect 123:1208
      1215; http://dx.doi.org/10.1289/ehp.1408675.

PMID- 25978620
TI  - Carboxy derivatised Ir(III) complexes: synthesis, electrochemistry, photophysical
      properties and photocatalytic hydrogen generation.
AB  - In this contribution the synthesis and characterisation of a series of novel
      mixed ligand iridium(iii) complexes, functionalised with a carboxy ester or
      phosphonate groups are reported. These groupings are introduced on the 4-position
      of either the phenyl pyridine or the 2,2'-bipyridyl ligands. A low temperature
      high yield synthesis for the precursor [Ir(ppy-COOEt)2(MU-Cl)]2 was developed.
      The photophysical and electrochemical properties of these compounds are also
      described, together with their behaviour as photosensitisers for the generation
      of hydrogen from water. 

PMID- 25978619
TI  - Quantitative Profiling of Lysine Acetylation Reveals Dynamic Crosstalk between
      Receptor Tyrosine Kinases and Lysine Acetylation.
AB  - Lysine acetylation has been primarily investigated in the context of
      transcriptional regulation, but a role for acetylation in mediating other
      cellular responses has emerged. Multiple studies have described global lysine
      acetylation profiles for particular biological states, but none to date have
      investigated the temporal dynamics regulating cellular response to perturbation.
      Reasoning that lysine acetylation may be altered in response to growth factors,
      we implemented quantitative mass spectrometry-based proteomics to investigate the
      temporal dynamics of lysine acetylation in response to growth factor stimulation
      in cultured carcinoma cell lines. We found that lysine acetylation changed
      rapidly in response to activation of several different receptor tyrosine kinases
      by their respective ligands. To uncover the effects of lysine acetylation
      dynamics on tyrosine phosphorylation signaling networks, cells were treated with
      an HDAC inhibitor. This short-term pharmacological inhibition of histone
      deacetylase activity modulated signaling networks involving phosphorylated
      tyrosine and thereby altered the response to receptor tyrosine kinase activation.
      This result highlights the interconnectivity of lysine acetylation and tyrosine
      phosphorylation signaling networks and suggests that HDAC inhibition may
      influence cellular responses by affecting both types of post-translational
      modifications. 

PMID- 25978621
TI  - Metallic Properties of the Si(111) - 5 * 2 - Au Surface from Infrared Plasmon
      Polaritons and Ab Initio Theory.
AB  - The metal-atom chains on the Si(111) - 5 * 2 - Au surface represent an
      exceedingly interesting system for the understanding of one-dimensional
      electrical interconnects. While other metal-atom chain structures on silicon
      suffer from metal-to-insulator transitions, Si(111) - 5 * 2 - Au stays metallic
      at least down to 20 K as we have proven by the anisotropic absorption from
      localized plasmon polaritons in the infrared. A quantitative analysis of the
      infrared plasmonic signal done here for the first time yields valuable band
      structure information in agreement with the theoretically derived data. The
      experimental and theoretical results are consistently explained in the framework
      of the atomic geometry, electronic structure, and IR spectra of the recent Kwon
      Kang model. 

PMID- 25978622
TI  - Sensitive detection of norovirus using phage nanoparticle reporters in lateral
      flow assay.
AB  - Noroviruses are recognized worldwide as the principal cause of acute, non
      bacterial gastroenteritis, resulting in 19-21 million cases of disease every year
      in the United States. Noroviruses have a very low infectious dose, a short
      incubation period, high resistance to traditional disinfection techniques and
      multiple modes of transmission, making early, point-of-care detection essential
      for controlling the spread of the disease. The traditional diagnostic tools,
      electron microscopy, RT-PCR and ELISA require sophisticated and expensive
      instrumentation, and are considered too laborious and slow to be useful during
      severe outbreaks. In this paper we describe the development of a new, rapid and
      sensitive lateral-flow assay using labeled phage particles for the detection of
      the prototypical norovirus GI.1 (Norwalk), with a limit of detection of 107 virus
      like particles per mL, one hundred-fold lower than a conventional gold
      nanoparticle lateral-flow assay using the same antibody pair. 

PMID- 25978623
TI  - Mesenteric artery responsiveness to acetylcholine and phenylephrine in cirrhotic
      rats challenged with endotoxin: the role of TLR4.
AB  - Cirrhosis is associated with vascular dysfunction and endotoxemia. These
      experiments were designed to investigate the hypothesis that the administration
      of a low-dose of lipopolysaccharide (LPS) worsens vascular dysfunction in rats
      subjected to bile-duct ligation (BDL), and to determine whether LPS initiates
      changes in vascular Toll-like receptor 4 (TLR4) expression. Four weeks after BDL,
      the animals were given an intraperitoneal injection of either saline or LPS (1.0
      mg/kg body mass). Three hours later, the superior mesenteric artery was isolated,
      perfused, and then subjected to the vasoconstriction and vasodilatation effects
      of phenylephrine and acetylcholine, respectively. Our results show that
      phenylephrine-induced vasoconstriction decreased in the cirrhotic vascular bed
      (BDL rats) compared with the vascular bed of the sham-operated animals, and that
      the LPS injections in the cirrhotic (BDL) rats worsened this response. LPS
      injection administered to the sham-operated animals had no such effect. On the
      other hand, both the BDL procedure and the LPS injection increased acetylcholine
      induced vasorelaxation, but LPS administration to the BDL rats had no effect on
      this response. The mRNA levels of TLR4 did not change, but immunohistochemical
      studies showed that TLR4 localization switched from the endothelium to vascular
      smooth muscle cells following chronic BDL. In conclusion, acute endotoxemia in
      cirrhotic rats is associated with hyporesponsiveness to phenylephrine and
      tolerance to the effects of acetylcholine. Altered localization of TLR4 may be
      responsible for these effects. 

PMID- 25978624
TI  - Entomological evaluation of PermaNet 2.0(r) and K-O Tab 1-2-3(r) treated nets in
      comparison to nets conventionally treated with deltamethrin, after repeated
      washing.
AB  - The residual insecticidal power of two types of ITNs (PermaNet 2.0(r) (PN2) and K
      O Tab 1-2-3(r) (KO 123)), compared to K-O Tab(r) (KO) treated nets, was assessed.
      The nets were tested unwashed, and after being washed, by hand 5, 15 and 21
      times, respectively. After each wash, the nets were dried vertically on a line,
      in the shade. Two types of bioassays (mean median knock down times (MMKDT) and
      mortality 24 hours after a 3-minute exposure (%mortality)) were used, along with
      reared female Anopheles stephensi. The number of washes had a great impact on
      MMKDT and %mortality of all types of nets. This impact was greater for
      conventionally treated nets, indicating that PN2 and KO 123 nets are
      significantly more wash resistant than KO nets after 21 washes. There was no
      significant difference between PN2 and KO 123 with respect to %mortality 24 hours
      after a 3-minute exposure at 0, 15 and 21 washes. Similarly, the same results
      were obtained for MMKDT, and the differences between PN2 and KO 123 were not
      statistically significant. This study demonstrates that the efficacy of KO 123
      nets is as beneficial as the efficacy of PN2 nets up to 21 washes.

PMID- 25978626
TI  - Interstitial lung disease related to smoking: imaging considerations.
AB  - PURPOSE OF REVIEW: To discuss the imaging of interstitial lung disease believed
      to be caused by smoking. RECENT FINDINGS: It is increasingly clear that smoking
      is associated with a variety of patterns of interstitial lung disease. The
      radiologic features of interstitial lung disease caused by smoking cigarettes are
      variable and may be nonspecific. SUMMARY: It is now accepted that cigarette
      smoking can cause lung diseases other than lung cancer, chronic bronchitis and
      emphysema. Indeed, the hypothesis that tobacco smoke can cause interstitial lung
      disease - and, specifically, pulmonary fibrosis - dates back to the 1960s. The
      list of interstitial lung disease, in which smoking is believed to have an
      etiologic role, includes Langerhans' cell histiocytosis, respiratory
      bronchiolitis/respiratory bronchiolitis-interstitial lung disease and
      desquamative interstitial pneumonia. More recently, there is emerging evidence
      which suggests that smoking may be associated with other patterns of pulmonary
      fibrosis (e.g. nonspecific interstitial pneumonia and smoking-related
      interstitial fibrosis). In the present review we discuss the imaging of the
      interstitial lung disease known to be caused by smoking; the typical appearances
      and some of the diagnostic difficulties are discussed.

PMID- 25978625
TI  - Video-assisted thoracoscopic surgery for retained hemothorax in blunt chest
      trauma.
AB  - PURPOSE OF REVIEW: In the last decade, video-assisted thoracoscopic surgery
      (VATS) has become a popular method in diagnosis and treatment of acute chest
      injuries. Except for patients with unstable vital signs who require larger
      surgical incisions to check bleeding, this endoscopic surgery could be employed
      in the majority of thoracic injury patients with stable vital signs. RECENT
      FINDINGS: In the past, VATS was used to evacuate traumatic-retained hemothorax.
      Recent study has revealed further that lung repair during VATS could decrease
      complications after trauma. Management of fractured ribs could also be assisted
      by VATS. Early VATS intervention within 7 days after injury can decrease the rate
      of posttraumatic infection and length of hospital stay. In studies of the
      pathophysiology of animal models, N-acetylcysteine and methylene blue were used
      in animals with blunt chest trauma and found to improve clinical outcomes.
      SUMMARY: Retained hemothorax derived from blunt chest trauma should be managed
      carefully and rapidly. Early VATS intervention is a well tolerated and reliable
      procedure that can be applied to manage this complication cost effectively.

PMID- 25978627
TI  - Physiology of breathlessness associated with pleural effusions.
AB  - PURPOSE OF REVIEW: Pleural effusions have a major impact on the cardiorespiratory
      system. This article reviews the pathophysiological effects of pleural effusions
      and pleural drainage, their relationship with breathlessness, and highlights key
      knowledge gaps. RECENT FINDINGS: The basis for breathlessness in pleural
      effusions and relief following thoracentesis is not well understood. Many
      existing studies on the pathophysiology of breathlessness in pleural effusions
      are limited by small sample sizes, heterogeneous design and a lack of direct
      measurements of respiratory muscle function. Gas exchange worsens with pleural
      effusions and improves after thoracentesis. Improvements in ventilatory capacity
      and lung volumes following pleural drainage are small, and correlate poorly with
      the volume of fluid drained and the severity of breathlessness. Rather than lung
      compression, expansion of the chest wall, including displacement of the
      diaphragm, appears to be the principle mechanism by which the effusion is
      accommodated. Deflation of the thoracic cage and restoration of diaphragmatic
      function after thoracentesis may improve diaphragm effectiveness and efficiency,
      and this may be an important mechanism by which breathlessness improves.
      Effusions do not usually lead to major hemodynamic changes, but large effusions
      may cause cardiac tamponade and ventricular diastolic collapse. Patients with
      effusions can have impaired exercise capacity and poor sleep quality and
      efficiency. SUMMARY: Pleural effusions are associated with abnormalities in gas
      exchange, respiratory mechanics, respiratory muscle function and hemodynamics,
      but the association between these abnormalities and breathlessness remains
      unclear. Prospective studies should aim to identify the key mechanisms of
      effusion-related breathlessness and predictors of improvement following pleural
      drainage.

PMID- 25978628
TI  - Malignant tracheal tumors: a review of current diagnostic and management
      strategies.
AB  - PURPOSE OF REVIEW: This article reviews the current literature for the purpose of
      developing a practical approach for the diagnosis and management of primary
      tracheal tumors. RECENT FINDINGS: Because of nonspecific symptoms, tracheal
      tumors remain a diagnostic challenge. Currently available management strategies
      are not being optimally utilized due to lack of physician awareness and
      knowledge. The use of newer diagnostic modalities has increased diagnostic
      accuracy resulting in earlier detection in recent years. This review describes
      currently available diagnostic modalities along with relatively newer ones such
      as virtual bronchoscopy, anatomic Optical Coherence Tomography, spectroscopic
      techniques, and endobronchial ultrasonography. We will review and discuss
      management strategies including surgical options, adjuvant therapies, and
      interventional pulmonary techniques including their role in palliation. SUMMARY:
      Early detection along with improved surgical and interventional pulmonology
      techniques has led to a decline in the death rates from tracheal cancer in recent
      years. However, further studies are required to define the role of
      chemotherapeutic agents, combination therapies, and novel techniques such as
      tracheal transplantation, in the management of primary tracheal tumors. More
      robust evidence-based studies are needed to provide evidence for clinical
      practice guidelines for the treatment of primary tracheal tumors.

PMID- 25978629
TI  - Update on F-18-fluoro-deoxy-glucose-PET/computed tomography in nonsmall cell lung
      cancer.
AB  - PURPOSE OF REVIEW: The aim of this review is to provide an outline of current
      evidence for the use of F-18-fluoro-deoxy-glucose PET computed tomography (FDG
      PET/CT) in nonsmall cell lung cancer (NSCLC) for diagnosis, staging, radiotherapy
      planning, response assessment and response monitoring. RECENT FINDINGS:
      Management of patients with NSCLC requires a multimodality approach to accurately
      diagnose and stage patients. In this approach, FDG-PET/CT has become a standard
      staging instrument in lung cancer. FDG-PET/CT is, in addition to staging, also
      valuable for the characterization of the solitary pulmonary nodule. An increased
      uptake in the nodule as compared with mediastinal blood pool is suspected for
      malignancy. In radiotherapy planning, FDG-PET/CT can assist the radiation
      oncologist for optimal dose delivery to the tumour, while sparing healthy
      tissues. Evidence of the prognostic and predictive implications of FDG-PET/CT is
      accumulating. Volumetric parameters of PET, such as metabolic active tumour
      volume and total lesion glycolysis, are promising predictive and prognostic
      biomarkers. However, for implementation of metabolic response parameters in
      clinical practice, more randomized, PET-based, multicentre trials are necessary.
      The introduction of integrated PET and MRI scanners did not change the pivotal
      role of standard FDG-PET/CT yet, as with current technology, PET/MRI did not show
      superior performance in thoracic staging. SUMMARY: The role of PET is described
      for diagnosis, staging and response assessment.

PMID- 25978630
TI  - Update in primary pulmonary lymphomas.
AB  - PURPOSE OF REVIEW: Despite the fact that primary pulmonary lymphoma (PPL) is a
      rare lung tumour, significant advances addressing clinical features, histological
      diagnosis, prognostic criteria and therapeutic management of this disease have
      been made within the past decade. RECENT FINDINGS: Monoclonality and phenotyping
      of alveolar lymphocytes are suggestive of mucosa-associated lymphoid tissue
      (MALT). Detection of MALT-1 gene rearrangements in bronchoalveolar fluid cells
      using fluorescence in-situ hybridization techniques helps to confirm the
      diagnosis of MALT PPL. Fine needle aspiration-computed tomography guided biopsies
      as well as transbronchial/cryobiopsies provide adequate tissue material for
      histological evaluation. Recent publications also provide a better appreciation
      of newer chemotherapeutic approaches, including fludarabine and mitoxantrone with
      or without ritubximab for the treatment of MALT, as well as complete surgical
      resection if local disease is present. Prognostic factors influencing survival
      and optimal therapy for MALT have not been well defined, but the use of tumour
      microvascular density appears promising. SUMMARY: This review outlines the
      implications of recent findings for clinical practice and research progress of
      PPL. Larger, multicentre and well designed studies are imperative to optimize the
      current diagnostic and therapeutic approach for this disease.

PMID- 25978631
TI  - Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose
      Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health
      (ELSA-Brasil).
AB  - INTRODUCTION: Observational studies have reported fairly consistent inverse
      associations between coffee consumption and risk of type 2 diabetes, but this
      association has been little investigated with regard to lesser degrees of
      hyperglycemia and other alterations in glucose homeostasis. Additionally, the
      association between coffee consumption and diabetes has been rarely investigated
      in South American populations. We examined the cross-sectional relationships of
      coffee intake with newly diagnosed diabetes and measures of glucose homeostasis,
      insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle
      aged and elderly individuals. METHODS: We used baseline data from 12,586
      participants of the Longitudinal Study of Adult Health (ELSA-Brasil). Logistic
      regression analyses were performed to examine associations between coffee
      consumption and newly diagnosed diabetes. Analysis of covariance was used to
      assess coffee intake in relation to two-hour glucose from an oral glucose
      tolerance test, fasting glucose, glycated hemoglobin, fasting and -2-hour
      postload insulin and measures of insulin sensitivity. RESULTS: We found an
      inverse association between coffee consumption and newly diagnosed diabetes,
      after adjusting for multiple covariates [23% and 26% lower odds of diabetes for
      those consuming coffee 2-3 and >3 times per day, respectively, compared to those
      reporting never or almost never consuming coffee, (p = .02)]. An inverse
      association was also found for 2-hour postload glucose [Never/almost never: 7.57
      mmol/L, <=1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12
      mol/L, p<0.0001] but not with fasting glucose concentrations (p = 0.07). Coffee
      was additionally associated with 2-hour postload insulin [Never/almost never:
      287.2 pmol/L, <=1 time/day: 280.1 pmol/L, 2-3 times/day: 275.3 pmol/L, >3
      times/day: 262.2 pmol/L, p = 0.0005) but not with fasting insulin concentrations
      (p = .58). CONCLUSION: Our present study provides further evidence of a
      protective effect of coffee on risk of adult-onset diabetes. This effect appears
      to act primarily, if not exclusively, through postprandial, as opposed to
      fasting, glucose homeostasis.

PMID- 25978632
TI  - Exploring the Feasibility of Service Integration in a Low-Income Setting: A Mixed
      Methods Investigation into Different Models of Reproductive Health and HIV Care
      in Swaziland.
AB  - Integrating reproductive health (RH) with HIV care is a policy priority in high
      HIV prevalence settings, despite doubts surrounding its feasibility and varying
      evidence of effects on health outcomes. The process and outcomes of integrated RH
      HIV care were investigated in Swaziland, through a comparative case study of four
      service models, ranging from fully integrated to fully stand-alone HIV services,
      selected purposively within one town. A client exit survey (n=602) measured
      integrated care received and unmet family planning (FP) needs. Descriptive
      statistics were used to assess the degree of integration per clinic and client
      demand for services. Logistic regression modelling was used to test the
      hypothesis that clients at more integrated sites had lower unmet FP needs than
      clients in a stand-alone site. Qualitative methods included in-depth interviews
      with clients and providers to explore contextual factors influencing the
      feasibility of integrated RH-HIV care delivery; data were analysed thematically,
      combining deductive and inductive approaches. Results demonstrated that clinic
      models were not as integrated in practice as had been claimed. Fragmentation of
      HIV care was common. Services accessed per provider were no higher at the more
      integrated clinics compared to stand-alone models (p>0.05), despite reported
      demand. While women at more integrated sites received more FP and pregnancy
      counselling than stand-alone models, they received condoms (a method of choice)
      less often, and there was no statistical evidence of difference in unmet FP needs
      by model of care. Multiple contextual factors influenced integration practices,
      including provider de-skilling within sub-specialist roles; norms of task
      oriented routinised HIV care; perceptions of heavy client loads; imbalanced
      client-provider interactions hindering articulation of RH needs; and provider
      motivation challenges. Thus, despite institutional support, factors related to
      the social context of care inhibited provision of fully integrated RH-HIV
      services in these clinics. Programmes should move beyond simplistic training and
      equipment provision if integrated care interventions are to be sustained. 

PMID- 25978634
TI  - Percolation on networks with conditional dependence group.
AB  - Recently, the dependence group has been proposed to study the robustness of
      networks with interdependent nodes. A dependence group means that a failed node
      in the group can lead to the failures of the whole group. Considering the
      situation of real networks that one failed node may not always break the
      functionality of a dependence group, we study a cascading failure model that a
      dependence group fails only when more than a fraction beta of nodes of the group
      fail. We find that the network becomes more robust with the increasing of the
      parameter beta. However, the type of percolation transition is always first order
      unless the model reduces to the classical network percolation model, which is
      independent of the degree distribution of the network. Furthermore, we find that
      a larger dependence group size does not always make the networks more fragile. We
      also present exact solutions to the size of the giant component and the critical
      point, which are in agreement with the simulations well. 

PMID- 25978633
TI  - Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly
      Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon
      Inducible Chemokines.
AB  - Autoimmune Addison's disease (AAD) is a disorder caused by an immunological
      attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is
      elevated in serum of AAD patients, suggesting a peripheral IFN signature.
      However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs,
      cytokines, or microbial components. We therefore investigated whether peripheral
      blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity
      to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I
      or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and
      CXCL9 were significantly elevated in patients compared with controls, IFN
      stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control
      PBMC. Low CXCL10 production was not significantly associated with medication,
      disease duration, or comorbidities, but the low production of poly (I:C)-induced
      CXCL10 among patients was associated with an AAD risk allele in the phosphatase
      nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN
      induced phosphorylated STAT1 and -2, were not significantly different between
      patients and controls. We conclude that PBMC from patients with AAD are deficient
      in their response to IFNs, and that the adrenal cortex itself may be responsible
      for the increased serum levels of CXCL10. 

PMID- 25978635
TI  - Interdisciplinary Differential Diagnosis and Care of a Patient with Atypical
      Delusional Parasitosis due to early HIV-related Dementia.
AB  - OBJECTIVE: To provide a differential diagnosis and recommendations for care for
      an individual with suspected delusional parasitosis secondary to human
      immunodeficiency virus (HIV). METHOD: A 62-year-old male with sexually acquired,
      chronic, and well-managed HIV infection was referred for neuropsychological
      evaluation and treatment recommendations following extensive self-manipulation of
      a sternoclavicular cystic mass and superficial skin lesions over most of his
      body. The patient reported that he had pulled long calcified tendrils out of the
      mass over a period of several weeks and that "encapsulated fat" was flowing
      beneath his skin. RESULTS: Numerous lab panels were negative for any acute
      medical pathology. Clinical neuroimaging was unremarkable. Neuropsychological
      evaluation revealed a profile consistent with mild neurocognitive disorder due to
      HIV. Medical and behavioral recommendations were made for the management of
      delusional thought processes consistent with atypical delusional parasitosis and
      other symptoms. The patient was responsive to carefully crafted provider feedback
      and his delusional and somatic symptoms decreased significantly with risperidone.
      CONCLUSIONS: This case illustrates the utility of neuropsychological assessment
      and provider feedback in the diagnosis and care of HIV-related neurocognitive
      disorder, the context of a delusional disorder.

PMID- 25978636
TI  - Composition, Shell Strength, and Metabolizable Energy of Mulinia lateralis and
      Ischadium recurvum as Food for Wintering Surf Scoters (Melanitta perspicillata).
AB  - Decline in surf scoter (Melanitta perspicillata) waterfowl populations wintering
      in the Chesapeake Bay has been associated with changes in the availability of
      benthic bivalves. The Bay has become more eutrophic, causing changes in the
      benthos available to surf scoters. The subsequent decline in oyster beds
      (Crassostrea virginica) has reduced the hard substrate needed by the hooked
      mussel (Ischadium recurvum), one of the primary prey items for surf scoters,
      causing the surf scoter to switch to a more opportune species, the dwarf surfclam
      (Mulinia lateralis). The composition (macronutrients, minerals, and amino acids),
      shell strength (N), and metabolizable energy (kJ) of these prey items were
      quantified to determine the relative foraging values for wintering scoters.
      Pooled samples of each prey item were analyzed to determine composition. Shell
      strength (N) was measured using a shell crack compression test. Total collection
      digestibility trials were conducted on eight captive surf scoters. For the prey
      size range commonly consumed by surf scoters (6-12 mm for M. lateralis and 18-24
      mm for I. recurvum), I. recurvum contained higher ash, protein, lipid, and energy
      per individual organism than M. lateralis. I. recurvum required significantly
      greater force to crack the shell relative to M. lateralis. No difference in
      metabolized energy was observed for these prey items in wintering surf scoters,
      despite I. recurvum's higher ash content and harder shell than M. lateralis.
      Therefore, wintering surf scoters were able to obtain the same amount of energy
      from each prey item, implying that they can sustain themselves if forced to
      switch prey. 

PMID- 25978637
TI  - Normal range albuminuria and metabolic syndrome in South Korea: the 2011-2012
      Korean National Health and Nutrition Examination Survey.
AB  - BACKGROUND: It is well-known that there is a close relationship between metabolic
      syndrome (MetS) and microalbuminuria. However, some recent studies have found
      that even normal range albuminuria was associated with MetS and cardiometabolic
      risk factors. The purpose of this study is to analyze the relationship between
      MetS and normal range albuminuria and to calculate the cutoff value for
      albuminuria that correlates with MetS in the representative fraction of Korean
      population. METHODS: Data were obtained from the 2011-2012 Korea National Health
      and Nutrition Examination Survey and included 9,650 subjects aged >= 19 years. We
      measured metabolic parameters: fasting blood glucose, waist circumference, blood
      pressure, and lipids, and albumin-to-creatinine ratio (ACR). The optimal ACR
      cutoff points for MetS were examined by the receiver operating characteristic
      curve. Multivariate logistic regression was used to obtain the prevalence of MetS
      and its components according to the ACR levels. RESULTS: The first cutoff value
      of ACR were 4.8 mg/g for subjects with >= 3 components of MetS. There was a
      graded association between ACR and prevalence of MetS and its components. If ACR
      was <4 mg/g, there was no significant increase in the prevalence of MetS or its
      components. From the ACR level of 4-5 mg/g, the prevalence of MetS significantly
      increased after adjusting for age, sex, body mass index, smoking, alcohol intake,
      exercise, and medications for diabetes mellitus and hypertension (odds ratio; 95%
      confidence intervals = 1.416; 1.041-1.926). CONCLUSIONS: Albuminuria within the
      normal range (around 5 mg/g) was associated with prevalence of MetS in the Korean
      population.

PMID- 25978638
TI  - Factors associated with increased survival after surgical resection of
      glioblastoma in octogenarians.
AB  - Elderly patients with glioblastoma represent a clinical challenge for
      neurosurgeons and oncologists. The data available on outcomes of patients greater
      than 80 undergoing resection is limited. In this study, factors linked to
      increased survival in patients over the age of 80 were analyzed. A retrospective
      chart review of all patients over the age of 80 with a new diagnosis of
      glioblastoma and who underwent surgical resection with intent for maximal
      resection were examined. Patients who had only stereotactic biopsies were
      excluded. Immunohistochemical expression of oncogenic drivers (p53, EGFR, IDH-1)
      and a marker of cell proliferation (Ki-67 index) performed upon routine
      neuropathological examination were recorded. Stepwise logistic regression and
      Kaplan Meier survival curves were plotted to determine correlations to overall
      survival. Fifty-eight patients fit inclusion criteria with a mean age of 83
      (range 80-93 years). The overall median survival was 4.2 months. There was a
      statistically significant correlation between Karnofsky Performance Status (KPS)
      and overall survival (P < 0.05). There was a significantly longer survival among
      patients undergoing either radiation alone or radiation and chemotherapy compared
      to those who underwent no postoperative adjuvant therapy (p < 0.05). There was
      also an association between overall survival and lack of p53 expression (p <
      0.001) and lack of EGFR expression (p <0.05). In this very elderly population,
      overall survival advantage was conferred to those with higher preoperative KPS,
      postoperative adjuvant therapy, and lack of protein expression of EGFR and p53.
      These findings may be useful in clinical decision analysis for management of
      patients with glioblastoma who are octogenarians, and also validate the critical
      role of EGFR and p53 expression in oncogenesis, particularly with advancing age. 

PMID- 25978639
TI  - Correction: do young children understand relative value comparisons?

PMID- 25978640
TI  - A rare co-segregation-mutation in the insulin receptor substrate 1 gene in one
      Chinese family with ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS; MIM 106300) is a common rheumatic disease with strong
      genetic components affecting approximately 0.3% of the population. The exact
      genetic mechanism of AS remains elusive. Our previous study showed that AS could
      be transmitted in an autosomal dominant inheritance mode and a 6-cM candidate
      region located on the chromosome 2q36.1-36.3 was mapped in a Chinese family.
      Mutation screening was conducted within the candidate region in the family and
      other AS by sequencing, and the novel mutation will be further validated in other
      AS families, sporadic cases and healthy controls by mass spectrometry. We
      identified a rare non-synonymous mutation (Arg580Gly) in insulin receptor
      substrate 1 (IRS1) co-segregated with disease phenotype in patients of the
      family, which was not found in other AS families, sporadic patients and healthy
      controls. In the study, we found a rare non-synonymous mutation in IRS1 co
      segregation in one Chinese family with AS, which indicated a new candidate
      disease causative gene for AS. 

PMID- 25978642
TI  - Enabling Rapid and Specific Surface-Enhanced Raman Scattering Immunoassay Using
      Nanoscaled Surface Shear Forces.
AB  - A rapid and simple approach is presented to address two critical issues of
      surface-enhanced Raman scattering (SERS)-based immunoassay such as
      removal/avoiding nonspecific adsorption and reducing assay time. The approach
      demonstrated involves rationally designed fluorophore-integrated gold/silver
      nanoshells as SERS nanotags and utilizes alternative current electrohydrodynamic
      (ac-EHD)-induced nanoscaled surface shear forces to enhance the capture kinetics.
      The assay performance was validated in comparison with hydrodynamic flow and
      conventional immunoassay-based devices. These nanoscaled physical forces acting
      within nanometer distances from the electrode surface enabled rapid (40 min),
      sensitive (10 fg/mL), and highly specific detection of human epidermal growth
      factor receptor 2 in breast cancer patient samples. We believe this approach
      presents potential for the development of rapid and sensitive SERS immunoassays
      for routine clinical diagnosis. 

PMID- 25978641
TI  - Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and
      Links DICER1 Loss to the Pathogenesis of Pleuropulmonary Blastoma.
AB  - Pleuropulmonary Blastoma (PPB) is the primary neoplastic manifestation of a
      pediatric cancer predisposition syndrome that is associated with several diseases
      including cystic nephroma, Wilms tumor, neuroblastoma, rhabdomyosarcoma,
      medulloblastoma, and ovarian Sertoli-Leydig cell tumor. The primary pathology of
      PPB, epithelial cysts with stromal hyperplasia and risk for progression to a
      complex primitive sarcoma, is associated with familial heterozygosity and lesion
      associated epithelial loss-of-heterozygosity of DICER1. It has been hypothesized
      that loss of heterozygosity of DICER1 in lung epithelium is a non-cell autonomous
      etiology of PPB and a critical pathway that regulates lung development; however,
      there are no known direct targets of epithelial microRNAs (miRNAs) in the lung.
      Fibroblast Growth Factor 9 (FGF9) is expressed in the mesothelium and epithelium
      during lung development and primarily functions to regulate lung mesenchyme;
      however, there are no known mechanisms that regulate FGF9 expression during lung
      development. Using mouse genetics and molecular phenotyping of human PPB tissue,
      we show that FGF9 is overexpressed in lung epithelium in the initial multicystic
      stage of Type I PPB and that in mice lacking epithelial Dicer1, or induced to
      overexpress epithelial Fgf9, increased Fgf9 expression results in pulmonary
      mesenchymal hyperplasia and a multicystic architecture that is histologically and
      molecularly indistinguishable from Type I PPB. We further show that miR-140 is
      expressed in lung epithelium, regulates epithelial Fgf9 expression, and regulates
      pseudoglandular stages of lung development. These studies identify an essential
      miRNA-FGF9 pathway for lung development and a non-cell autonomous signaling
      mechanism that contributes to the mesenchymal hyperplasia that is characteristic
      of Type I PPB. 

PMID- 25978643
TI  - Intake of Erythrocytes Required for Reproductive Development of Female
      Schistosoma japonicum.
AB  - The reproductive development and maturation of female schistosomes are crucial
      since their released eggs are responsible for the host immunopathology and
      transmission of schistosomiasis. However, little is known about the nutrients
      required by female Schistosoma japonicum during its sexual maturation. We
      evaluated the promoting effect of several nutrients (calf serum, red blood cells
      (RBCs), ATP and hypoxanthine) on the reproductive development of pre-adult
      females at 18 days post infection (dpi) from mixed infections and at 50 dpi from
      unisexual infections of laboratory mice in basic medium RPMI-1640. We found RBCs,
      rather than other nutrients, promoted the female sexual maturation and egg
      production with significant morphological changes. In 27% of females (18 dpi)
      from mixed infections that paired with males in vitro on day 14, vitelline glands
      could be positively stained by Fast Blue B; and in 35% of females (50 dpi) from
      unisexual infections on day 21, mature vitelline cells were observed. Infertile
      eggs were detected among both groups. To analyze which component of mouse RBCs
      possesses the stimulating effect, RBCs were fractionated and included in media.
      However, the RBC fractions failed to stimulate development of the female
      reproductive organs. In addition, bovine hemoglobin hydrolysate, digested by
      neutral protease, was found to exhibit the promoting activity instead of
      untreated bovine hemoglobin. The other protein hydrolysate, lactalbumin
      hydrolysate, exhibited a similar effect with bovine hemoglobin hydrolysate. Using
      quantitative RT-PCR, we found the expression levels of four reproduction-related
      genes were significantly stimulated by RBCs. These data indicate that RBCs
      provide essential nutrients for the sexual maturation of female S. japonicum and
      that the protein component of RBCs appeared to constitute the key nutrient. These
      findings would improve laboratory culture of pre-adult schistosomes to adult
      worms in medium with well-defined components, which is important to investigate
      the function of genes related to female sexual maturation. 

PMID- 25978645
TI  - Binding mode of inhibitors and Cryptosporidium parvum IMP dehydrogenase: A
      combined ligand- and receptor-based study.
AB  - A combined ligand- and target-based approach was used to analyse the interaction
      models of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase (CpIMPDH)
      with selective inhibitors. First, a ligand-based pharmacophore model was
      generated from 20 NAD(+) competitive CpIMPDH inhibitors with the HipHop module.
      The characteristic of the NAD(+) binding site of CpIMPDH was then described, and
      the binding modes of the representative inhibitors were studied by molecular
      docking. The combination of the pharmacophore model and the docking results
      allowed us to evaluate the pharmacophore features and structural information of
      the NAD(+) binding site of CpIMPDH. This research supports the proposal of an
      interaction model inside the NAD(+) binding site of CpIMPDH, consisting of four
      key interaction points: two hydrophobic-aromatic groups, a hydrophobic-aliphatic
      group and a hydrogen bond donor. This study also provides guidance for the design
      of more potent CpIMPDH inhibitors for the treatment of Cryptosporidium
      infections.

PMID- 25978644
TI  - Pre- and postnatal exposure to moderate levels of ethanol can have long-lasting
      effects on hippocampal glutamate uptake in adolescent offspring.
AB  - The developing brain is vulnerable to the effects of ethanol. Glutamate is the
      main mediator of excitatory signals in the brain and is probably involved in most
      aspects of normal brain function during development. The aim of this study was to
      investigate vulnerability to and the impact of ethanol toxicity on glutamate
      uptake signaling in adolescent rats after moderate pre and postnatal ethanol
      exposure. Pregnant female rats were divided into three groups and treated only
      with water (control), non-alcoholic beer (vehicle) or 10% (v/v) beer solution
      (moderate prenatal alcohol exposure-MPAE). Thirty days after birth, adolescent
      male offspring were submitted to hippocampal acute slice procedure. We assayed
      glutamate uptake and measured glutathione content and also quantified glial
      glutamate transporters (EAAT 1 and EAAT 2). The glutamate system vulnerability
      was tested with different acute ethanol doses in naive rats and compared with the
      MPAE group. We also performed a (lipopolysaccharide-challenge (LPS-challenge)
      with all groups to test the glutamate uptake response after an insult. The MPAE
      group presented a decrease in glutamate uptake corroborating a decrease in
      glutathione (GSH) content. The reduction in GSH content suggests oxidative damage
      after acute ethanol exposure. The glial glutamate transporters were also altered
      after prenatal ethanol treatment, suggesting a disturbance in glutamate
      signaling. This study indicates that impairment of glutamate uptake can be dose
      dependent and the glutamate system has a higher vulnerability to ethanol toxicity
      after moderate ethanol exposure In utero. The effects of pre- and postnatal
      ethanol exposure can have long-lasting impacts on the glutamate system in
      adolescence and potentially into adulthood. 

PMID- 25978646
TI  - Ethnicity- and sex-based discrimination and the maintenance of self-esteem.
AB  - The psychological underpinnings of labor market discrimination were investigated
      by having participants from Israel, the West Bank and Germany (N = 205) act as
      employers in a stylized employment task in which they ranked, set wages, and
      imposed a minimum effort level on applicants. State self-esteem was measured
      before and after the employment task, in which applicant ethnicity and sex were
      salient. The applicants were real people and all behavior was monetarily
      incentivized. Supporting the full self-esteem hypothesis of the social identity
      approach, low self-esteem in women was associated with assigning higher wages to
      women than to men, and such behavior was related to the maintenance of self
      esteem. The narrower hypothesis that successful intergroup discrimination serves
      to protect self-esteem received broader support. Across all participants, both
      ethnicity- and sex-based discrimination of out-groups were associated with the
      maintenance of self-esteem, with the former showing a stronger association than
      the latter. 

PMID- 25978647
TI  - ABO Blood Type and Personality Traits in Healthy Japanese Subjects.
AB  - There is no scientific consensus that a relationship exists between the ABO blood
      group and personality traits. However, a recent study hypothesized that the
      dopamine beta-hydroxylase (DBH) gene is in linkage with the ABO gene. The sample
      population consisted of 1,427 healthy Japanese subjects who completed the
      Temperament and Character Inventory (TCI). Each subject's ABO blood type was
      determined by genotyping the rs8176719 and rs8176746 ABO gene single-nucleotide
      polymorphisms (SNPs) using a TaqMan genotyping assay. The relationships between
      the six ABO genotypes or four ABO phenotypes and personality traits were examined
      using a multivariate analysis of covariance (MANCOVA), controlling for age and
      sex. The MANCOVA data showed a significant difference in TCI scores among the ABO
      genotype groups (F [7, 1393] = 3.354, p = 0.001). A subsequent univariate
      analysis showed a significant difference in the mean scores for Persistence among
      the genotype groups (F = 2.680, partial eta2 = 0.010, p = 0.020). Similarly,
      dividing the ABO blood type into four phenotypes revealed a significant
      difference among the phenotype groups (F [7, 1397] = 2.529, p = 0.014). A
      subsequent univariate analysis showed a significant difference among the
      phenotype groups in the mean scores for Persistence (F = 2.952, partial eta2=
      0.006, p = 0.032). We observed a significant association between ABO blood group
      genotypes and personality traits in a large number of healthy Japanese subjects.
      However, these results should be regarded as preliminary and should be
      interpreted with caution because it is possible that the association between ABO
      blood group genotype and the Persistence trait is relatively weak. 

PMID- 25978648
TI  - Dynamically orienting your own face facilitates the automatic attraction of
      attention.
AB  - We report two experiments showing that dynamically orienting our own face
      facilitates the automatic attraction of attention. We had participants complete a
      cueing task where they had to judge the orientation of a lateralized target cued
      by a central face that dynamically changed its orientation. Experiment 1 showed a
      reliable cueing effect from both self- and friend-faces at a long stimulus onset
      asynchrony (SOA), however, the self-faces exclusively generated a spatial cueing
      effect at a short SOA. In Experiment 2, event-related potential (ERP) data to the
      face cues showed larger amplitudes in the N1 component for self-faces relative to
      friend- and unfamiliar-faces. In contrast, the amplitude of the P3 component was
      reduced for self compared with friend- and unfamiliar-other cues. The size of the
      self-bias effect in N1 correlated with the strength of self-biases in P3. The
      results indicate that dynamic changes in the orientation of one's own face can
      provide a strong ecological cue for attention, enhancing sensory responses (N1)
      and reducing any subsequent uncertainty (P3) in decision-making.

PMID- 25978649
TI  - The flavone apigenin blocks nuclear translocation of sterol regulatory element
      binding protein-2 in the hepatic cells WRL-68.
AB  - Sterol regulatory element-binding protein-2 (SREBP-2) is a pivotal
      transcriptional factor in cholesterol metabolism. Factors interfering with the
      proper functioning of SREBP-2 potentially alter plasma lipid concentrations.
      Consuming fruits and vegetables is associated with beneficial plasma lipid
      profile. The mechanism by which plant foods induce desirable lipid changes
      remains unclear. Apigenin, a common plant food flavonoid, was shown to modulate
      the nuclear translocation of SREBP-2 in the hepatic cells WRL-68 in the present
      study. The processing of SREBP-2 protein occurred after translation, and apigenin
      blocked this activation route. Further examination indicated that AMP-activated
      protein kinase (AMPK) was activated by the flavone, and co-administrating the
      AMPK-specific inhibitor compound C could release the blockage. Reporter gene
      assay revealed that the transactivation of sterol responsive element (SRE)
      containing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) promoter was
      suppressed by the flavone. Similarly, electromobility shift assay result also
      demonstrated a reduced DNA-binding activity on the SRE domain under the same
      treatment. The reduced transactivity and DNA-binding activity could be attributed
      to a decreased amount of SREBP-2 translocating from cytosol to nucleus as
      depicted by confocal microscopy. Quantitative RT-PCR assay demonstrated that the
      transcription of HMGCR followed the same pattern of SREBP-2 translocation. In
      summary, the present study showed that apigenin prevented SREBP-2 translocation
      and reduced the downstream gene HMGCR transcription. The minimum effective dosage
      should be achievable in the form of functional food consumption or dietary
      supplementation. 

PMID- 25978650
TI  - Internal migration, area effects and health: Does where you move to impact upon
      your health?
AB  - Evidence surrounding the importance of neighbourhood on health has been mostly
      restricted to observational data analyses. However, observational data are often
      the only source of information available to test this association and can fail to
      accurately draw out casual effects. This study employs a pseudo-experimental
      design to provide a novel test for the evidence of neighbourhood effects on
      health, using migration as a mechanism for assessing the role of neighbourhood.
      Coarsened exact matching was employed on the British Household Panel Survey (2006
      2008) to analyse the association between migration (by area type, measured using
      a classification of mortality patterns) and health. Although an overall
      significant positive association between migration and health was observed, once
      the effect was disaggregated by location and destination it disappeared. Rather,
      evidence of health selective migration was found whereby individuals of poorer
      health migrated to areas that displayed poorer health and social characteristics
      (and vice versa). Migration is an important process that through the social
      sorting of individuals in terms of their health, contributes to the growing
      polarisation and inequality in health patterns. The study helps to build upon
      previous research through providing a new and stronger form of analysis that
      reduces the influence of bias on results. Incorporating this under-utilised
      methodology and research design in future studies could help develop public
      health and geographical research. 

PMID- 25978651
TI  - Interfacing low-energy SAW nebulization with Liquid Chromatography-Mass
      Spectrometry for the analysis of biological samples.
AB  - Soft ionization methods for the introduction of labile biomolecules into a mass
      spectrometer are of fundamental importance to biomolecular analysis. Previously,
      electrospray ionization (ESI) and matrix assisted laser desorption-ionization
      (MALDI) have been the main ionization methods used. Surface acoustic wave
      nebulization (SAWN) is a new technique that has been demonstrated to deposit less
      energy into ions upon ion formation and transfer for detection than other methods
      for sample introduction into a mass spectrometer (MS). Here we report the
      optimization and use of SAWN as a nebulization technique for the introduction of
      samples from a low flow of liquid, and the interfacing of SAWN with liquid
      chromatographic separation (LC) for the analysis of a protein digest. This
      demonstrates that SAWN can be a viable, low-energy alternative to ESI for the LC
      MS analysis of proteomic samples. 

PMID- 25978652
TI  - Starch-Based Layer by Layer Assembly: Efficient and Sustainable Approach to
      Cotton Fire Protection.
AB  - Starch has been employed via layer by layer assembly for building an efficient
      and sustainable biobased coatings capable of protecting cotton from fire. In
      order to obtain a better understanding of the coating to substrate relationship,
      the coating efficiency has been tested on cotton fabrics having different
      densities (i.e., 100, 200, and 400 g/m(2)). The adopted deposition conditions
      allow for the buildup of a homogeneous coating even at a low number of deposition
      steps. The physical and chemical mechanisms are described and related to the
      achieved results. The coating can greatly enhance the char forming ability of
      cellulose, nearly doubling the amount of thermally stable organic residue
      produced by cotton at high temperatures, as assessed by thermogravimetric
      analyses. After only 2 bilayers deposited, this biobased system is capable of
      self-extinguishing a flame during flammability tests with less than 5% in weight
      deposited on cotton. This high efficiency is kept even when the coating is
      deposited on cotton with the highest density. By cone calorimetry, all treated
      cottons showed significant reductions (up to 40%) of the total heat released
      during combustion, thus demonstrating the high efficiency achieved. 

PMID- 25978653
TI  - Silencing of Receptor Tyrosine Kinase ROR1 Inhibits Tumor-Cell Proliferation via
      PI3K/AKT/mTOR Signaling Pathway in Lung Adenocarcinoma.
AB  - Receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, is
      expressed in certain hematological malignancies and solid tumors, but is
      generally absent in adult tissues. This makes the protein an ideal drug target
      for cancer therapy. In order to assess the suitability of ROR1 as a cell surface
      antigen for targeted therapy of lung adenocarcinoma, we carried out a
      comprehensive analysis of ROR1 protein expression in human lung adenocarcinoma
      tissues and cell lines. Our data show that ROR1 protein is selectively expressed
      on lung adenocarcinoma cells, but do not support the hypothesis that expression
      levels of ROR1 are associated with aggressive disease. However silencing of ROR1
      via siRNA treatment significantly down-regulates the activity of the
      PI3K/AKT/mTOR signaling pathway. This is associated with significant apoptosis
      and anti-proliferation of tumor cells. We found ROR1 protein expressed in lung
      adenocarcinoma but almost absent in tumor-adjacent tissues of the patients. The
      finding of ROR1-mediated proliferation signals in both tyrosine kinase inhibitor
      (TKI)-sensitive and -resistant tumor cells provides encouragement to develop ROR1
      directed targeted therapy in lung adenocarcinoma, especially those with TKI
      resistance. 

PMID- 25978654
TI  - Neohesperidin Dihydrochalcone versus CCl4-Induced Hepatic Injury through
      Different Mechanisms: The Implication of Free Radical Scavenging and Nrf2
      Activation.
AB  - Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to
      the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act
      against CCl4-induced hepatic injury, but its mechanism is still unclear. We first
      discovered that NHDC showed a strong ability to scavenge free radicals. In
      addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1)
      and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear
      factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE)
      signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in
      the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the
      ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated
      protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal
      kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK)
      phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed
      its protective antioxidant effect against CCl4-induced oxidative damage via the
      direct free radical scavenging and indirect Nrf2/ARE signaling pathway. 

PMID- 25978655
TI  - Superior Versus Inferior Vestibular Neuritis: Are There Intrinsic Differences in
      Infection, Reactivation, or Production of Infectious Particles Between the
      Vestibular Ganglia?
AB  - HYPOTHESIS: Intrinsic differences in neurons of the vestibular ganglia result in
      the increased likelihood of superior vestibular ganglion involvement in
      vestibular neuritis. BACKGROUND: Vestibular neuritis is hypothesized to result
      from herpes simplex type I (HSV1) infection or reactivation in vestibular
      ganglia. Involvement of the inferior vestibular ganglion is extremely rare in
      patients with vestibular neuritis. METHODS: Primary cultures of rat superior and
      inferior vestibular ganglion neurons (VGNs) were cultivated separately. Neurons
      were lytically and latently infected with HSV1 with a US11-green fluorescent
      protein (GFP) chimera. Percentage lytic infection and baseline reactivation was
      assessed by microscopy for GFP fluorescence. Trichostatin-A (TSA) was used to
      stimulate HSV1 reactivation. Virion production was assessed by viral titers.
      Relative numbers of latency-associated (LAT) transcripts were determined by real
      time reverse-transcription polymerase chain reaction (real-time RT-PCR). RESULTS:
      Lytic infection rates were equivalent between the two ganglia (p > 0.05). Lytic
      infections yielded similar amounts of plaque-forming units (p > 0.05). Relative
      amounts of LAT transcripts did not differ between latently infected superior and
      inferior VGNs. Latently infected cultures showed no differences in rates of
      baseline and TSA-induced HSV1 reactivation (p > 0.05). Production of virions was
      not significantly different between reactivated, latently infected superior
      versus inferior VGNs (p = 0.45). CONCLUSION: Differences in prevalence of
      superior and inferior vestibular neuritis do not result from intrinsic
      differences in HSV1 infection or virion production of these neurons. Other
      factors, such as the length and width of the bony canal containing the ganglia
      and nerves, account for the greater involvement of the superior vestibular
      ganglion in vestibular neuritis.

PMID- 25978656
TI  - No Own-Age Advantage in Children's Recognition of Emotion on Prototypical Faces
      of Different Ages.
AB  - We test whether there is an own-age advantage in emotion recognition using
      prototypical younger child, older child and adult faces displaying emotional
      expressions. Prototypes were created by averaging photographs of individuals from
      6 different age and sex categories (male 5-8 years, male 9-12 years, female 5-8
      years, female 9-12 years, adult male and adult female), each posing 6 basic
      emotional expressions. In the study 5-8 year old children (n = 33), 9-13 year old
      children (n = 70) and adults (n = 92) labelled these expression prototypes in a 6
      alternative forced-choice task. There was no evidence that children or adults
      recognised expressions better on faces from their own age group. Instead, child
      facial expression prototypes were recognised as accurately as adult expression
      prototypes by all age groups. This suggests there is no substantial own-age
      advantage in children's emotion recognition. 

PMID- 25978657
TI  - Reduced Graphene Oxide/Amaranth Extract/AuNPs Composite Hydrogel on Tumor Cells
      as Integrated Platform for Localized and Multiple Synergistic Therapy.
AB  - Integration of multimodal treatment strategies combined with localized therapy to
      enhance antitumor efficacy and reduce side effects is still a challenge. Herein,
      a novel composite hydrogel containing rGO, amaranth extract (AE) and gold
      nanoparticles (AuNPs) was prepared by using AE as both reductant and cross
      linking agent. The chlorophyll derivatives in AE were also employed as a
      photodynamic therapy drug. Meanwhile, AuNPs and rGO both have obvious
      photothermal effects and can accelerate the generation of cytotoxic singlet
      oxygen (1O2). The temperature increase of rGO/AE/AuNPs precursor is up to 6.3 
      degrees C under 808 nm laser irradiation at a power density of 200 mW.cm(-2). The
      hydrogel shell on in situ tumor cells was easily formed and regulated by near
      infrared irradiation within 10 min, which could both retain a high concentration
      of drugs on the lesion site and prevent them from migrating to normal tissue,
      thus reducing the side effects. Compared with rGO/AE and AE, rGO/AE/AuNPs showed
      a remarkably improved and synergistic antitumor effect. The hydrogel possesses
      good biocompatibility and high hydrophilicity and could be used for loading
      chemotherapeutics, which provides a new approach for located and multiple
      antitumor therapies.

PMID- 25978658
TI  - Toxic erythema of chemotherapy following leukemia cutis.
AB  - A 56-year-old Caucasian male newly diagnosed with acute myelogenous leukemia
      (AML) M3 presented with a six-week history of multiple painful erythematous
      nodules scattered on his trunk and extremities, previously treated as abscesses
      with incision and drainage plus oral trimethoprim-sulfamethoxazole without
      improvement. A punch biopsy was performed, and the histopathology and
      immunostaining profile were compatible with leukemia cutis secondary to AML.
      Induction chemotherapy for AML with cytarabine, etoposide, and mitoxantrone was
      initiated. Dermatology was reconsulted two weeks later for evaluation and
      treatment of a new eruption on both dorsal hands and wrists that began three days
      after starting induction chemotherapy. On physical exam, there were well
      demarcated erythematous patches and plaques with mild induration on the hands,
      extending onto the distal forearms and sparing the dorsal metacarpalphalangeal
      joints and ventral wrists. Biopsy findings were consistent with toxic erythema of
      chemotherapy, likely secondary to cytarabine. 

PMID- 25978659
TI  - Delayed detection of a ventricular septal defect following penetrating trauma.
AB  - This is a case report of a 27-year-old male who sustained a stab wound to the
      chest with a resulting penetrating cardiac injury and subsequent emergency
      thoracotomy. The patient survived his injury and on post-op day two, a
      holosystolic murmur was noted during physical exam, but he remained
      hemodynamically stable and intubated. A transthoracic echocardiogram revealed the
      presence of a ventricular septal defect (VSD), with Doppler flow revealing
      shunting from the left ventricular cavity into the right ventricular cavity.
      Ultimately, the clinicians decided upon a trial of extubation with a plan for
      delayed closure of the VSD. Upon extubation,the patient became hypoxemic with
      evidence of pulmonary edema; thus, he was re-intubated. The defect was surgically
      repaired, and the patient had an uneventful recovery thereafter. The purpose of
      this case report is to present an example of delayed detection of a ventricular
      septal defect after a penetrating cardiac injury. 

PMID- 25978660
TI  - Psychopharmacological treatment of delirium: does earlier treatment and scheduled
      dosing improve outcomes?
AB  - PURPOSE: The goals of this study were to examine how dosing strategies and
      timeliness of antipsychotic medication initiation would affect delirium duration.
      METHODS: This is a retrospective paper and electronic record review of patients
      in an academic hospital who had been diagnosed with delirium. Forty-two patients
      met inclusion criteria. Quantitative and qualitative data on the course of
      delirium was gathered, as well as important demographic and medical variables.
      RESULTS: There were no significant differences in duration of delirium between
      the scheduled and PRN groups using survival analysis, although the test was
      marginally significant (log rank test, p<0.06). Those who received treatment
      within 24 hours of recognition had significantly shorter durations of delirium
      compared to those who began treatment after 24 hours (log rank test, p<0.006).
      CONCLUSION: These data suggest that early psychopharmacological treatment of
      delirium can reduce duration. Future research needs to investigate prompt and
      scheduled medication dosing strategies for treatment of delirium symptoms.

PMID- 25978661
TI  - A 36-year-old male with a painless lower extremity skin lesion.

PMID- 25978662
TI  - Limited circumferential dissection of the ascending aorta mimicking an acute
      coronary syndrome.

PMID- 25978663
TI  - Inclusion body myositis masquerading as cardiac dyspnea.
AB  - Dyspnea in the elderly can be due to a wide array of pathologies. We discuss a
      case of an elderly gentleman with an extensive cardiovascular history presenting
      with acute worsening of chronic dyspnea. Because of persistent respiratory
      distress unresponsive to standard therapy for congestive heart failure,
      chronotropic insufficiency, and pulmonary hypertension, further evaluation was
      undertaken which revealed that diaphragmatic weakness was the etiology of his
      respiratory failure. EMG and muscle biopsy confirmed the diagnosis of inclusion
      body myositis (IBM). 

PMID- 25978664
TI  - Broken lung.
AB  - We report a case of severe acute respiratory distress syndrome (ARDS) complicated
      by a very large bronchopleural fistula (BPF) measuring 30 mm in length and
      evident on computed tomography (CT) chest scan. Such a large BPF is a very rare
      occurrence. Generally, a BPF of more than 6 mm in size is considered as large.(1)
      Small BPFs can be easily missed on CT scan chest, but a persistent air-leak
      through an adequately placed chest tube should raise suspicion for a BPF. 

PMID- 25978665
TI  - ECG Case of the Month. ECG in a 44-Year-Old Man With Chest Pain. DIAGNOSIS: Arm
      lead reversal; normal sinus rhythm; right atrial enlargement and right
      ventricular enlargement suggesting an ostium secundum atrial septal defect; acute
      inferior myocardial infarction.

PMID- 25978666
TI  - Radiology case of the month. An Uncommon Chest Wall Mass in Renal Disease.
      RADIOLOGICAL DIAGNOSIS: Tumoral Calcinois with Fluid-Fluid Levels.

PMID- 25978667
TI  - CLINICAL CASE OF THE MONTH. A 63-Year-Old Woman With Rash and Proximal Muscle
      Weakness.
AB  - A 63-year-old woman with a history of infiltrating ductal breast cancer, status
      post-mastectomy and chemotherapy, was in remission for 18 months prior to being
      admitted to the hospital with complaints of a pruritic erythematous macular rash
      involving her head, chest, and bilateral upper and lower extremities. Along with
      the dermatologic manifestations, physical exam revealed proximal symmetrical
      muscle weakness and bilateral axillary lymphadenopathy. Initial workup for muscle
      weakness revealed a creatine kinase of 2,200 IU/L (normal 20-180 IU/L). After
      administration of intravenous fluids for renal protection, serum sodium dropped
      to 121 mEQ/L (normal 135-145 mEQ/L). Computed tomography of the chest showed
      axillary and supraclavicular lymphadenopathy. Biopsy of a supraclavicular node
      revealed infiltrating ductal cancer with histologic and morphologic
      characteristics similar to her previous breast cancer. Following an extensive
      laboratory workup, we concluded that our patient's myositis and hyponatremia were
      paraneoplastic syndromes secondary to her recurrent breast cancer. 

PMID- 25978668
TI  - PATHOLOGY IMAGE OF THE MONTH. Autopsy Findings in an Adult with Down Syndrome.
AB  - Emergency medical responders were activated to the home of a 59-year-old African
      American male in distress and with known Down syndrome complicated by Alzheimer's
      disease. He was found to be unresponsive and subsequently became pulseless.
      Advanced cardiac life support protocols were initiated and continued for two
      hours in the emergency department. Due to family request, efforts were eventually
      ceased and the patient was declared dead. Full, unrestricted autopsy examination
      was conducted under the coroner's authorization. The cause of death was
      determined to be a pulmonary thromboembolus in the main pulmonary artery with
      extension into the bilateral pulmonary arteries. Additional external findings
      included alopecia universalis, penoscrotal hypospadias, ostium secundum type of
      atrial septal defect, right ventricular cardiac dilatation, diffuse cerebral
      atrophy, facial features compatible with Down syndrome, and generalized patches
      of skin depigmentation over the hands as seen in Figure 1 but also over the feet,
      lips, areola, and trunk. Microscopic findings included features of pulmonary
      hypertension. A microscopic image from a section of the thyroid is seen in Figure
      2.

PMID- 25978670
TI  - Homogeneity and composition of AlInGaN: A multiprobe nanostructure study.
AB  - The electronic properties of quaternary AlInGaN devices significantly depend on
      the homogeneity of the alloy. The identification of compositional fluctuations or
      verification of random-alloy distribution is hence of grave importance. Here, a
      comprehensive multiprobe study of composition and compositional homogeneity is
      presented, investigating AlInGaN layers with indium concentrations ranging from 0
      to 17at% and aluminium concentrations between 0 and 39 at% employing high-angle
      annular dark field scanning electron microscopy (HAADF STEM), energy dispersive X
      ray spectroscopy (EDX) and atom probe tomography (APT). EDX mappings reveal
      distributions of local concentrations which are in good agreement with random
      alloy atomic distributions. This was hence investigated with HAADF STEM by
      comparison with theoretical random alloy expectations using statistical tests. To
      validate the performance of these tests, HAADF STEM image simulations were
      carried out for the case of a random-alloy distribution of atoms and for the case
      of In-rich clusters with nanometer dimensions. The investigated samples, which
      were grown by metal-organic vapor phase epitaxy (MOVPE), were thereby found to be
      homogeneous on this nanometer scale. Analysis of reconstructions obtained from
      APT measurements yielded matching results. Though HAADF STEM only allows for the
      reduction of possible combinations of indium and aluminium concentrations to the
      proximity of isolines in the two-dimensional composition space. The observed
      ranges of composition are in good agreement with the EDX and APT results within
      the respective precisions. 

PMID- 25978671
TI  - Determination of three-dimensional strain state in crystals using self-interfered
      split HOLZ lines.
AB  - An experimental method to measure the strain through the thickness of a crystal
      is demonstrated. This enables the full three-dimensional stress-strain state of a
      crystal at the nanoscale to be determined taking the current practice from two
      dimensional strain state determination. Knowing the 3D strain state is desired by
      crystal growers in order to improve their crystal's quality. This method involves
      combining electron diffraction with electron interferometry in a transmission
      electron microscope. The electron diffraction uses a split higher order Laue zone
      (HOLZ) line and the electron interferometry uses an electron biprism. 

PMID- 25978669
TI  - Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During
      Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.
AB  - Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the
      aseptic trauma of surgery. We hypothesized that rats with MetaS would have
      dysregulated inflammation, increased lung injury, and less effective
      antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to
      rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity
      runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48
      h, inflammatory mediators and bacteria were quantified in the blood,
      bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed
      histologically. BALF protein and lung wet-dry ratios were quantified to assess
      for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats
      had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in
      plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs.
      Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although
      lactate levels, and liver and renal function tests were similar between groups,
      LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced
      acute lung injury histologically. During S. aureus bacteremia, as compared with
      HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses,
      accompanied by increased acute lung injury and vascular leak. Notably, despite an
      augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in
      their blood and lungs. The MetaS state may exacerbate lung injury and vascular
      leak by attenuating the inflammation-resolving response, and by weakening
      antimicrobial defenses. 

PMID- 25978672
TI  - Caring for the carer: a systematic review of pure technology-based cognitive
      behavioral therapy (TB-CBT) interventions for dementia carers.
AB  - BACKGROUND: Face-to-face delivery of CBT is not always optimal or practical for
      informal dementia carers (DCs). Technology-based formats of CBT delivery (TB-CBT)
      have been developed with the aim to improve client engagement and accessibility,
      and lower delivery costs, and offers potential benefits for DCs. However,
      research of TB-CBT for DCs has maintained heavy reliance on therapist
      involvement. The efficacy of pure TB-CBT interventions for DCs is not currently
      established Methods: A systematic review of trials of pure TB-CBT intervention
      for DCs from 1995 was conducted. PsycINFO, Cochrane Reviews, Scopus and MedLine
      databases were searched using key terms related to CBT, carers and dementia. Four
      hundred and forty two articles were identified, and inclusion/exclusion criteria
      were applied; studies were only retained if quantitative data was available, and
      there was no active therapist contact. Four articles were retained; two
      randomized and two waitlist control trials. Methodological and reporting quality
      was assessed. Meta-analyses were conducted for the outcome measures of caregiver
      depression. RESULTS: Meta-analysis revealed small significant post-intervention
      effects of pure TB-CBT interventions for depression; equivalent to face-to-face
      interventions. However, there is no evidence regarding long-term efficacy of pure
      TB-CBT for DCs. The systematic review further identified critical methodological
      and reporting shortcomings pertaining to these trials Conclusions: Pure TB-CBT
      interventions may offer a convenient, economical method for delivering
      psychological interventions to DCs. Future research needs to investigate their
      long-term efficacy, and consider potential moderating and mediating factors
      underpinning the mechanisms of effect of these programs. This will help to
      provide more targeted interventions to this underserviced population.

PMID- 25978674
TI  - Specific anion effects in Artemia salina.
AB  - The specific anion effect on the vitality of Artemia salina was investigated by
      measuring the Lethal Time LT50 of the crustaceans in the presence of different
      sodium salts solutions at room temperature and at the same ionic strength as
      natural seawater. Fluoride, thiocyanate and perchlorate are the most toxic
      agents, while chloride, bromide and sulfate are well tolerated. The rates of
      oxygen consumption of brine shrimps were recorded in mixed NaCl+NaF or NaCl+NaSCN
      solutions as a function of time. The results are discussed in terms of the
      Hofmeister series, and suggest that, besides the biochemical processes that
      involve F(-), SCN(-) and ClO4(-), the different physico-chemical properties of
      the strong kosmotropic and chaotropic anions may contribute in determining their
      strong toxicity for A. salina. 

PMID- 25978673
TI  - A meta-analysis of site-specific effects of cathodal transcranial direct current
      stimulation on sensory perception and pain.
AB  - The primary aim of our meta-analysis was to evaluate the effects of cathodal
      transcranial direct current stimulation (c-tDCS) on sensory and pain thresholds
      (STh and PTh) in healthy individuals and pain level (PL) in patients with chronic
      pain. Electronic databases were searched for c-tDCS studies. Methodological
      quality was evaluated using the PEDro and Downs and Black (D&B) assessment tools.
      C-tDCS of the primary motor cortex (S1) increases both STh (P<0.001, effect size
      of 26.84%) and PTh (P<0.001, effect size of 11.62%). In addition, c-tDCS over M1
      led to STh increase (P<0.005, effect size of 30.44%). Likewise, PL decreased
      significantly in the patient group following application of c-tDCS. The small
      number of studies precluded subgroup analysis. Nevertheless, meta-analysis showed
      that in all groups (except c-tDCS of S1) active c-tDCS and sham stimulation
      produced significant differences in STh/PTh in healthy and PL in patient group.
      This review provides evidence for the site-specific effectiveness of c-tDCS in
      increasing STh/PTh in healthy individuals and decreasing PL in patients with
      chronic pain. However, due to small sample sizes in the included studies, our
      results should be interpreted with caution. Given that the level of blinding was
      not considered in the inclusion criteria, the results of the current study should
      be interpreted with caution. 

PMID- 25978675
TI  - Understanding the implications of dissolved organic carbon when assessing
      antagonism in vitro: An example with an estrogen receptor assay.
AB  - Both estrogenic and anti-estrogenic activity has been observed in water samples.
      Some studies have suggested that dissolved organic carbon (DOC), which can be co
      extracted during sample enrichment, contributes to the apparent antagonistic
      effect. DOC has a high sorption capacity for the estrogen receptor (ER) agonist
      17beta-estradiol, which may reduce the available 17beta-estradiol concentration
      in the antagonist testing mode and potentially lead to apparent antagonism. The
      aim of the study was to determine the influence of DOC when assessing antagonism
      in an ER reporter gene assay. The presence of DOC shifted the 17beta-estradiol
      concentration-effect curve to higher concentrations, increasing the nominal EC50
      value by up to 0.3 log units. However, this shift was within the usual
      variability associated with repeated measurements of concentration-effect curves.
      This shift was not due to DOC being an antagonist itself or interfering with
      fluorescence measurements, but was due to DOC reducing the bioavailability of
      17beta-estradiol. This was demonstrated by modelling the DOC sorption corrected
      17beta-estradiol concentration using experimental DOC-water partition
      coefficients (KDOC). While the shift in the 17beta-estradiol concentration-effect
      curve was minor, sorption of 17beta-estradiol to DOC can have an impact when
      assessing antagonism. At the EC50 agonist concentration, both modelled and
      experimental results showed that DOC at concentrations similar to that co
      extracted in water samples caused suppression of the agonist at levels that would
      be classified as antagonism. The suppression was less pronounced at the EC80
      agonist concentration, hence this is recommended when assessing antagonism of DOC
      rich samples, such as surface water and wastewater. 

PMID- 25978677
TI  - Controllable synthesis of various kinds of copper sulfides (CuS, Cu7S4, Cu9S5)
      for high-performance supercapacitors.
AB  - Three types of copper sulfides including CuS, Cu7S4 and Cu9S5 were successfully
      synthesized at different concentrations of ethylenediamine in a liquid phase
      synthesis process. The whole shape evolution of Cu7S4 microstructures could be
      manipulated by adjusting the concentration of ethylenediamine. This study
      indicates that the coordination chemistry of ethylenediamine ligands and copper
      cations exerts vital effects on the formation of the dendritic structure.
      Furthermore, experimental conditions such as the reaction temperature and time
      are also observed to have an impact on the morphology of copper sulfides. The
      structures of Cu7S4 with snowflake-like morphology provided special paths for ion
      diffusion. Therefore, apart from the excellent discharge rate and good stability,
      Cu7S4 also exhibits a high specific capacitance of 1303.01 F g(-1) at a current
      density of 5 A g(-1). 

PMID- 25978678
TI  - They can interact, but can they learn? Toddlers' transfer learning from
      touchscreens and television.
AB  - Despite the ubiquity of touchscreen applications and television programs for
      young children, developmental research suggests that learning in this context is
      degraded relative to face-to-face interactions. Most previous research has been
      limited to transfer of learning from videos, making it difficult to isolate the
      relative perceptual and social influences for transfer difficulty, and has not
      examined whether the transfer deficit persists across early childhood when task
      complexity increases. The current study examined whether the transfer deficit
      persists in older children using a complex puzzle imitation task constructed to
      investigate transfer from video demonstrations. The current test adapted this
      task to permit bidirectional transfer from touchscreens as well. To test for
      bidirectional transfer deficits, 2.5- and 3-year-olds were shown how to assemble
      a three-piece puzzle on either a three-dimensional magnetic board or a two
      dimensional touchscreen (Experiment 1). Unidirectional transfer from video was
      also tested (Experiment 2). Results indicate that a bidirectional transfer
      deficit persists through 3 years, with younger children showing a greater
      transfer deficit; despite high perceptual similarities and social engagement,
      children learned less in transfer tasks, supporting the memory flexibility
      account of the transfer deficit. Implications of these findings for use of screen
      media (e.g., video, tablets) in early education are discussed. 

PMID- 25978676
TI  - Genome-Wide Definition of Promoter and Enhancer Usage during Neural Induction of
      Human Embryonic Stem Cells.
AB  - Genome-wide mapping of transcriptional regulatory elements is an essential tool
      for understanding the molecular events orchestrating self-renewal, commitment and
      differentiation of stem cells. We combined high-throughput identification of
      transcription start sites with genome-wide profiling of histones modifications to
      map active promoters and enhancers in embryonic stem cells (ESCs) induced to
      neuroepithelial-like stem cells (NESCs). Our analysis showed that most promoters
      are active in both cell types while approximately half of the enhancers are cell
      specific and account for most of the epigenetic changes occurring during neural
      induction, and most likely for the modulation of the promoters to generate cell
      specific gene expression programs. Interestingly, the majority of the promoters
      activated or up-regulated during neural induction have a "bivalent" histone
      modification signature in ESCs, suggesting that developmentally-regulated
      promoters are already poised for transcription in ESCs, which are apparently pre
      committed to neuroectodermal differentiation. Overall, our study provides a
      collection of differentially used enhancers, promoters, transcription starts
      sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs,
      and a broad, genome-wide description of promoter and enhancer usage and of gene
      expression programs characterizing the transition from a pluripotent to a neural
      restricted cell fate. 

PMID- 25978679
TI  - A redox-responsive mesoporous silica nanoparticle capped with amphiphilic
      peptides by self-assembly for cancer targeting drug delivery.
AB  - A redox-responsive mesoporous silica nanoparticle (RRMSN) was developed as a drug
      nanocarrier by noncovalent functionalization of MSNs with amphiphilic peptides
      containing the RGD ligand. The alkyl chain stearic acid (C18) with a thiol
      terminal group was anchored on the surface of MSNs via a disulfide bond, and the
      amphiphilic peptide (AP) C18-DSDSDSDSRGDS was coated by self-assembly through
      hydrophobic interactions between the octadecyl groups of MSNs and alkyl chains of
      AP, which played the role of a gatekeeper collectively. In vitro drug release
      profiles demonstrated that the anticancer drug (DOX) could be entrapped with
      nearly no leakage in the absence of dithiothreitol (DTT) or glutathione (GSH).
      With the addition of DTT or GSH, the entrapped drug released quickly due to the
      cleavage of the disulfide bond. It was found that after the internalization of
      MSNs by cancer cells via the receptor-mediated endocytosis, the surface
      amphiphilic peptides and alkyl chain of RRMSN/DOX were removed to induce rapid
      drug release intracellularly after the cleavage of the disulfide bond, triggered
      by GSH secreted in cancer cells. This novel intelligent RRMSN/DOX drug delivery
      system using self-assembly of amphiphilic peptides around the MSNs provides a
      facile, but effective strategy for the design and development of smart drug
      delivery for cancer therapy. 

PMID- 25978680
TI  - Probing the Conformational and Functional Consequences of Disulfide Bond
      Engineering in Growth Hormone by Hydrogen-Deuterium Exchange Mass Spectrometry
      Coupled to Electron Transfer Dissociation.
AB  - Human growth hormone (hGH), and its receptor interaction, is essential for cell
      growth. To stabilize a flexible loop between helices 3 and 4, while retaining
      affinity for the hGH receptor, we have engineered a new hGH variant (Q84C/Y143C).
      Here, we employ hydrogen-deuterium exchange mass spectrometry (HDX-MS) to map the
      impact of the new disulfide bond on the conformational dynamics of this new hGH
      variant. Compared to wild type hGH, the variant exhibits reduced loop dynamics,
      indicating a stabilizing effect of the introduced disulfide bond. Furthermore,
      the disulfide bond exhibits longer ranging effects, stabilizing a short alpha
      helix quite distant from the mutation sites, but also rendering a part of the
      alpha-helical hGH core slightly more dynamic. In the regions where the hGH
      variant exhibits a different deuterium uptake than the wild type protein,
      electron transfer dissociation (ETD) fragmentation has been used to pinpoint the
      residues responsible for the observed differences (HDX-ETD). Finally, by use of
      surface plasmon resonance (SPR) measurements, we show that the new disulfide bond
      does not compromise receptor affinity. Our work highlight the analytical
      potential of HDX-ETD combined with functional assays to guide protein
      engineering. 

PMID- 25978681
TI  - Differential protein expression profiles of cyst fluid from papillary thyroid
      carcinoma and benign thyroid lesions.
AB  - Cystic papillary thyroid carcinoma (cPTC) is a subgroup of PTC presenting a
      diagnostic challenge at fine needle aspiration biopsy (FNAB). To further
      investigate this entity we aimed to characterize protein profiles of cyst fluids
      from cPTC and benign thyroid cystic lesions. In total, 20 cPTCs and 56 benign
      thyroid cystic lesions were studied. Profiling by liquid chromatography tandem
      mass spectrometry (LC-MS/MS) was performed on cyst fluids from a subset of cases
      after depletion, and selected proteins were further analyzed by Western blot
      (WB), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). A
      total of 1,581 proteins were detected in cyst fluids, of which 841 were
      quantified in all samples using LC-MS/MS. Proteins with different expression
      levels between cPTCs and benign lesions were identified by univariate analysis
      (41 proteins) and multivariate analysis (59 proteins in an orthogonal partial
      least squares model). WB analyses of cyst fluid and IHC on corresponding tissue
      samples confirmed a significant up-regulation of cytokeratin 19 (CK-19/CYFRA 21
      1) and S100A13 in cPTC vs. benign lesions. These findings were further confirmed
      by ELISA in an extended material of non-depleted cyst fluids from cPTCs (n = 17)
      and benign lesions (n = 55) (p<0.05). Applying a cut-off at >55 ng/ml for CK-19
      resulted in 82% specificity and sensitivity. For S100A13 a cut-off at >230 pg/ml
      revealed a 94% sensitivity, but only 35% specificity. This is the first
      comprehensive catalogue of the protein content in fluid from thyroid cysts. The
      up-regulations of CK-19 and S100A13 suggest their possible use in FNAB based
      preoperative diagnostics of cystic thyroid lesions. 

PMID- 25978683
TI  - Effects of personal experiences on the interpretation of the meaning of colours
      used in the displays and controls in electric control panels.
AB  - A survey was conducted to examine how personal experiences affect the
      interpretation of the meaning of display and control colours on electric control
      panels (ECPs). In Korea, the red light on ECPs represents a normal state of
      operation, while the green light represents a stopped state of operation; this
      appears to contradict the general stereotypes surrounding these colours. The
      survey results indicated that the participants who had experience in using ECPs
      interpreted the colour meaning differently from the other participant group. More
      than half of the experienced participants regarded the coloured displays and
      controls as they were designed, while most participants in the other group
      appeared to interpret the colours in accordance with the stereotypes. It is
      presumed that accidents related to human errors can occur when non-experienced
      people use the ECPs, which are easily accessible in many buildings. Practitioner
      Summary: A survey was conducted to investigate how personal experiences affect
      the interpretation of the function meanings of coloured lights on electrical
      control panels. It was found that the interpretation varies according to personal
      experiences, which can induce accidents related to human errors while operating
      electrical equipment.

PMID- 25978682
TI  - Smoking is associated with more abdominal fat in morbidly obese patients.
AB  - INTRODUCTION: While the association between cigarette smoking and abdominal fat
      has been well studied in normal and overweight patients, data regarding the
      influence of tobacco use in patients with morbid obesity remain scarce. The aim
      of this study is to evaluate body fat distribution in morbidly obese smokers.
      METHODS: We employed a cross-sectional study and grouped severely obese patients
      (body mass index [BMI] >40 kg/m2 or >35 kg/m2 with comorbidities) according to
      their smoking habits (smokers or non-smokers). We next compared the
      anthropometrical measurements and body composition data (measured by electric
      bioimpedance) of both groups. We analyzed the effect of smoking on body
      composition variables using univariate and multiple linear regression (MLR);
      differences are presented as regression coefficients (b) and their respective 95%
      confidence intervals. RESULTS: We included 536 morbidly obese individuals, 453
      (84.5%) non-smokers and 83 (15.5%) smokers. Male smokers had a higher BMI (b=3.28
      kg/m2, p=0.036), larger waist circumference (b=6.07 cm, p=0.041) and higher
      percentage of body fat (b=2.33%, p=0.050) than non-smokers. These differences
      remained significant even after controlling for confounding factors. For females,
      the only significant finding in MLR was a greater muscle mass among smokers
      (b=1.34kg, p=0.028). No associations were found between tobacco load measured in
      pack-years and anthropometric measures or body composition. DISCUSSION: Positive
      associations between smoking and BMI, and waist circumference and percentage of
      body fat, were found among male morbidly obese patients, but not among females.
      To the best of our knowledge, this study is the first investigation of these
      aspects in morbidly obese subjects. We speculate that our findings may indicate
      that the coexistence of morbid obesity and smoking helps to explain the more
      serious medical conditions, particularly cardiovascular diseases and neoplasms,
      seen in these patients.

PMID- 25978685
TI  - SMAS Debulking for Management of the Thick-Skinned Nose.

PMID- 25978684
TI  - Response of the maxillary dentition to a statically determinate one-couple system
      with tip-back mechanics: A prospective clinical trial.
AB  - OBJECTIVE: To quantify the effects of tip-back mechanics on the maxillary first
      molars and incisors. MATERIALS AND METHODS: Sixteen subjects with Class II end-on
      malocclusion were treated with an intrusion arch to achieve distalization of the
      maxillary molar through tip-back mechanics. Lateral cephalograms were taken prior
      to molar tip-back (T1), after molar tip-back (T2), and after molar root
      uprighting (T3). Data were analyzed using the Friedman's and Wilcoxon signed rank
      tests to evaluate differences in time points (P <= .016). RESULTS: The maxillary
      first molar distalized 1.53 mm (P = .001) with 6.65 degrees  (P = .001) of distal
      tipping and 0.86 mm (P = .001) of extrusion at T2. Minor relapse of the first
      molar (mesial direction) was seen at T3. The maxillary incisors flared labially
      0.4 mm, and the incisor root apex moved palatally 1.19 mm (P = .005) at T2. At
      T3, the incisor root apex moved palatally 1.5 mm (P = .003) from T1. An angular
      change from T1 of 3.31 degrees  (P = .008) and 3.53 degrees  (P = .014) was seen
      at T2 and T3, respectively, as a result of palatal root movement of the maxillary
      incisors. CONCLUSIONS: A significant amount of distalization of maxillary molars
      was attained at the crown level with tip-back mechanics. Palatal root angulation
      change was significant in the incisors with minimal anteroposterior movement of
      the incisal edge.

PMID- 25978687
TI  - Dispersion, solvent and metal effects in the binding of gold cations to alkynyl
      ligands: implications for Au(I) catalysis.
AB  - The coordination modes of the [Au(PPh3)](+) cation to metal alkynyl complexes
      have been investigated. On addition to ruthenium, a vinylidene complex,
      [Ru(eta(5)-C5H5)(PPh3)2([double bond, length as m-dash]C[double bond, length as m
      dash]CPh{AuPPh3})](+), is obtained while addition to a gold(iii) compound gives
      di- and trinuclear gold complexes depending on the conditions employed. In the
      trinuclear species, a gold(i) cation is sandwiched between two gold(iii) alkynyl
      complexes, suggesting that coordination of multiple C-C triple bonds to gold is
      facile. 

PMID- 25978686
TI  - Submerged macrophytes mitigate direct and indirect insecticide effects in
      freshwater communities.
AB  - Understanding how ecological interactions mitigate the impacts of perturbations
      such as pesticides in biological communities is an important basic and applied
      question for ecologists. In aquatic ecosystems, new evidence from microcosm
      experiments suggests that submerged macrophytes can buffer cladocerans from pulse
      exposures to the widely used insecticide malathion, and that mitigation increases
      with macrophyte density. However, whether these results scale up to more complex
      aquatic communities where ecological interactions such as competition can alter
      toxicity is unknown. Further, macrophyte abilities to mitigate different
      insecticide exposure scenarios (i.e. single versus repeated pulses) have never
      been tested. To address these gaps, we performed a factorial mesocosm experiment
      examining the influence of four macrophyte treatments (0, 10, 50, or 100 Elodea
      Canadensis shoots planted per mesocosm) crossed with three malathion exposure
      scenarios (no insecticide, single pulse, repeated pulses) on aquatic communities
      containing zooplankton, phytoplankton, periphyton, two snail species, and larval
      amphibians. In the absence of macrophytes, single malathion pulses caused short
      term declines in cladoceran abundance followed by their rapid recovery, which
      precluded any indirect effects (i.e. trophic cascades). However, repeated
      malathion pulses caused cladoceran extinctions, resulting in persistent
      phytoplankton blooms and reduced abundance of one snail species. In contrast,
      with macrophytes present, even at low density, malathion had no effect on any
      taxa. We also discovered novel effects of macrophytes on the benthic food web. In
      the two highest macrophyte treatments, we observed trends of reduced periphyton
      biomass, decreased abundance of one snail species, and decreased amphibian time
      to and mass at metamorphosis. To our knowledge, this is the first evidence of
      negative submerged macrophyte effects on amphibians, a taxa of global
      conservation concern. Our findings suggest that facilitating macrophytes could be
      an important strategy for buffering freshwater communities from insecticides,
      though consideration of their impacts on animal species is necessary. 

PMID- 25978688
TI  - Effect of 12 Weeks of Whole-Body Vibration Versus Multi-Component Training in
      Post-Menopausal Women.
AB  - The aims of this study were to analyze the effects of two different training
      protocols-vibratory platform and multi-component training--and to determine what
      kind of training creates greater adaptations on bone density and isokinetic
      strength of the knee extensors and the stabilizer muscles of the ankle joint in
      post-menopausal women. Thirty-eight women (59.8 +/- 6.2 years) were randomly
      assigned to whole-body vibration group (WBVG), multi-component training group
      (MTG), or a control group (CG). The experimental groups performed incremental
      training for 12 weeks, three sessions/week. Significant differences were found in
      total fat mass and total lean mass in the training groups. In addition, both WBVG
      and MTG showed significant increases in isokinetic strength for knee extensors at
      60 degrees .s(-1) and at 270 degrees .s(-1). With respect to the ankle joint, a
      significant increase for eversion at 60 degrees .s(-1) and inversion at 60
      degrees .s(-1) was found in both training groups, and eversion at 120 degrees .s(
      1) only in WBVG (p = 0.012). There were no significant differences between WBVG
      and MTG in knee and ankle strength tests. Therefore, we found significant
      adaptations to whole-body vibration and multi-component training in the present
      study. However, the improvements were similar for both groups and we cannot claim
      that WBVG is better than MTG, or vice versa.

PMID- 25978689
TI  - Octacoordinated Dioxo-Molybdenum Complex via Formal Oxidative Addition of
      Molecular Oxygen. Studies of Chemical Reactions Between M(CO)6 (M = Cr, Mo) and
      2,4-Di-tert-butyl-6-(pyridin-2-ylazo)-phenol.
AB  - Reactions of M(CO)6 (M = Mo, Cr) and 2 mol of 2,4-di-tert-butyl-6-(pyridin-2
      ylazo)-phenol ligand (HL) in air yielded [Mo(VI)O2(L(1)-)2], 1, and [Cr(III)(L(1)
      )(L(*2)-)], 2, respectively, in high yields. Formation of the Cr-complex is a
      substitution reaction, which is associated with electron transfer, while that of
      Mo is an example of molecular oxygen activation. Isolated monoradical chromium
      complex 2 is susceptible to oxidation. Accordingly the reaction of 2 with the
      oxidant, I2 produces a cationic nonradical complex of chemical composition
      [Cr(III)(L(1)-)2]I3, [2]I3 in almost quantitative yield. All the isolated
      complexes are primarily characterized by various spectroscopic techniques and
      magnetic measurements. While the molybdenum complex is diamagnetic, the two
      chromium complexes behave as simple paramagnets: MUeff (295 K), 2.81 MUB and 3.79
      MUB for 2 and [2]I3, respectively. Single-crystal three-dimensional X-ray
      structures of 1, 2, [2]I3 are reported. The geometry of the Mo-complex is square
      antiprism (octacoordination), and that of the Cr-complexes is distorted
      octahedral. Redox properties of the complexes are studied by cyclic voltammetry
      and constant potential coulometry. The data are analyzed based on density
      functional theoretical calculations of molecular orbitals of redox isomers of the
      Cr complexes. The results indicated that the redox events in the complexes occur
      at the ligand center. The oxidation state of Cr in 2 is further assessed by XPS
      measurements and compared with the reported systems. 

PMID- 25978690
TI  - Antiarrhythmic Effect of Either Negative Modulation or Blockade of Small
      Conductance Ca2+-activated K+ Channels on Ventricular Fibrillation in Guinea Pig
      Langendorff-perfused Heart.
AB  - During recent years, small conductance Ca-activated K (SK) channels have been
      reported to play a role in cardiac electrophysiology. SK channels seem to be
      expressed in atria and ventricles, but from a functional perspective, atrial
      activity is predominant. A general notion seems to be that cardiac SK channels
      are predominantly coming into play during arrhythmogenic events where
      intracellular concentration of Ca is increased. During ventricular fibrillation
      (VF), a surge of [Ca]i has the potential to bind to and open SK channels. To
      obtain mechanistic insight into possible roles of SK channels during VF, we
      conducted experiments with an SK channel pore blocker (ICA) and a negatively
      allosteric modulator (NS8395) in a Langendorff-perfused heart model. Both
      compounds increased the action potential duration, effective refractory period,
      and Wenckebach cycle length to comparable extents. Despite these similarities,
      the SK channel modulator was found to revert and prevent VF more efficiently than
      the SK channel pore blocker. In conclusion, either negative allosteric modulation
      of the SK channel with NS8593 is more favorable than pure channel block with ICA
      or the 2 compounds have different selectivity profiles that makes NS8593 more
      antiarrhythmic than ICA in a setting of VF. 

PMID- 25978691
TI  - Novel K+ Channel Targets in Atrial Fibrillation Drug Development--Where Are We?
AB  - There is a clear unmet medical need for new pharmacologic therapies with improved
      efficacy and safety for the treatment of atrial fibrillation. Considerable
      research efforts have been undertaken to discover and develop new safe and
      effective antiarrhythmic drugs that specifically target atrial K(+) channels. To
      realize the full value of these novel atrial-specific therapeutic drug targets,
      demonstration of clinical efficacy and safety is required for a new breed of
      atrial-selective antiarrhythmic drugs. The reward for demonstrating this in a
      pivotal phase III trial, on regulatory approval, will be "first-in-class" status.
      This article reviews the development status of new and novel K channel inhibitors
      currently in drug development as atrial-selective antiarrhythmics for the
      treatment of atrial fibrillation.

PMID- 25978692
TI  - The Significance of Neuregulin-1/ErbB Expression in Autogenous Vein Grafts in a
      Diabetic Rat Model.
AB  - Diabetes mellitus (DM) is an important risk factor for increased vein graft
      failure after bypass surgery. The neuregulin-1 (NRG-1)/ErbB signaling system
      plays a critical role in neointimal formation after vascular injury as well as
      the proliferation and migration of mitogen-induced vascular smooth muscle cells;
      however, changes in NRG-1/ErbB signaling leading to vein grafts attrition in DM
      remain largely unexplored. Therefore, the aim of this study was to investigate
      changes in NRG-1/ErbB signaling in vein grafts in diabetic rats. To do this, a
      rat model of DM was established by streptozotocin injection followed by
      engraftment of autologous jugular veins to carotid arteries to induce intimal
      hyperplasia. After vein graft harvest, a pathohistological examination was
      performed; changes in NRG-1 and ErbB expression were also assessed. NRG-1 and
      ErbB expression localized to endothelial cells and vascular smooth muscle cells,
      which is consistent with the arterialization of vein grafts. NRG-1, ErbB2, and
      ErbB4 expression significantly decreased in vein grafts over time. Our findings
      show that NRG-1/ErbB signaling is impaired in vein grafts of diabetic rats,
      suggesting an important role for this pathway in the pathogenesis of intimal
      hyperplastic lesions in vein grafts of patients with DM. 

PMID- 25978693
TI  - Chemical Protein Synthesis Using a Second-Generation N-Acylurea Linker for the
      Preparation of Peptide-Thioester Precursors.
AB  - The broad utility of native chemical ligation (NCL) in protein synthesis has
      fostered a search for methods that enable the efficient synthesis of C-terminal
      peptide-thioesters, key intermediates in NCL. We have developed an N-acylurea
      (Nbz) approach for the synthesis of thioester peptide precursors that efficiently
      undergo thiol exchange yielding thioester peptides and subsequently NCL reaction.
      However, the synthesis of some glycine-rich sequences revealed limitations, such
      as diacylated products that can not be converted into N-acylurea peptides. Here,
      we introduce a new N-acylurea linker bearing an o-amino(methyl)aniline (MeDbz)
      moiety that enables in a more robust peptide chain assembly. The generality of
      the approach is illustrated by the synthesis of a pentaglycine sequence under
      different coupling conditions including microwave heating at coupling
      temperatures up to 90 C, affording the unique and desired N-acyl-N'
      methylacylurea (MeNbz) product. Further extension of the method allowed the
      synthesis of all 20 natural amino acids and their NCL reactions. The kinetic
      analysis of the ligations using model peptides shows the MeNbz peptide rapidly
      converts to arylthioesters that are efficient at NCL. Finally, we show that the
      new MeDbz linker can be applied to the synthesis of cysteine-rich proteins such
      the cyclotides Kalata B1 and MCoTI-II through a one cyclization/folding step in
      the ligation/folding buffer. 

PMID- 25978694
TI  - Coupling Mediated Coherent Control of Localized Surface Plasmon Polaritons.
AB  - We investigate the phase-dependent excitation of localized surface plasmon
      polaritons in coupled nanorods by using nonlinear spectroscopy. Our design of a
      coupled three-nanorod structure allows independent excitation with cross
      polarized light. Here, we show that the excitation of a particular plasmon mode
      can be coherently controlled by changing the relative phase of two orthogonally
      polarized light fields. Furthermore, we observe a phase relation for the
      excitation that is dominantly caused by damping effects. 

PMID- 25978695
TI  - Synthesis of the MoS2@CuO heterogeneous structure with improved photocatalysis
      performance and H2O adsorption analysis.
AB  - MoS2@CuO heterogeneous structure nanoflowers were synthesized through a two-step
      hydrothermal method for the first time. The valence band offset (VBO) and
      conduction band offset (CBO) of the MoS2@CuO heterojunction, and the bases for
      the design of the heterogeneous structure were determined by X-ray photoemission
      spectroscopy (XPS). For the increased specific surface area and the formation of
      staggered type-II band alignment of the composite structure, a significantly
      enhanced photocatalytic ability of the MoS2@CuO heterojunction was obtained by
      studying the photodegradation of methylene blue (MB). After irradiation for 100
      min, the residual MB in solution was about 27.5% for pristine MoS2 nanoflowers
      while it was 4.3% for MoS2@CuO hetero-nanoflowers, respectively. The humidity
      sensing properties of the two nanostructures were also studied for comparison.
      The results showed that better response/recover times were obtained. In order to
      give a theoretical explanation for this phenomenon, we performed first-principles
      calculation to analyse the corresponding humidity sensing mechanisms of MoS2 and
      MoS2@CuO in detail. The calculated results showed that water molecules could bind
      stronger to the CuO surface compared to MoS2, which is in line with the
      experimental observations. 

PMID- 25978696
TI  - The Effects of Barefoot and Shod Running on Limb and Joint Stiffness
      Characteristics in Recreational Runners.
AB  - The authors aimed to determine the effects of barefoot (BF) and several
      commercially available barefoot-inspired (BFIS) footwear models on limb and joint
      stiffness characteristics compared with conventional footwear (CF). Fifteen male
      participants ran over a force platform at 4.0 m.s(-1), in BF, BFIS, and CF
      conditions. Measures of limb and joint stiffness were calculated for each
      footwear. The results indicate that limb and knee stiffness were greater in BF
      and minimalist BFIS than in CF. CF and more structured BFIS were associated with
      a greater ankle stiffness compared with BF and minimalist BFIS. These findings
      serve to provide further insight into the susceptibility of runners to different
      injury mechanisms as a function of footwear. 

PMID- 25978697
TI  - Chemical composition, antioxidant and antibacterial properties of Pteranthus
      dichotomus from Algerian Sahara.
AB  - The phytochemical study of ethyl acetate and n-butanol extracts of Pteranthus
      dichotomus Forssk. led to the isolation and identification of 11 compounds,
      including three glycolipids 1-3, one lignan 4, three flavonoids 5-7 and four
      phytosterols 8-11. Structures of the isolated compounds have been elucidated by
      analysis of 1D and 2D NMR data, and mass spectrometry EI-MS and ESI-MS and by
      comparison with literature data. Furthermore, the ethyl acetate and n-butanol
      extracts were examined for their antioxidant and antibacterial activities. The
      results showed that both extracts (PDAC and PDBU) had a moderate antioxidant
      activity (IC50 = 375.514 MUg/mL and 691.333 MUg/mL) respectively.

PMID- 25978698
TI  - Evaluation of a comprehensive information and assistance program for patients
      with schizophrenia treated with long-acting injectable antipsychotics.
AB  - OBJECTIVE: While atypical long-acting injectable antipsychotics (LAIs) offer the
      potential for increased adherence, access to medication poses challenges that may
      hinder their use. Janssen Connect * *Janssen Connect is a registered trade name
      of Janssen Scientific Affairs, LLC, Titusville, NJ, USA. (JC), a comprehensive
      information and assistance program, was designed to help patients who received a
      Janssen LAI initiate and maintain treatment after their health care professional
      (HCP) determined that the medication was the most clinically appropriate option.
      We conducted a formative and impact evaluation on early medication adherence of
      patients enrolled in JC and prescribed paliperidone palmitate. METHODS: Using the
      program administrative files (December 2010-April 2014), 9354 patients whose HCP
      ordered paliperidone palmitate were included. Patient demographics, clinical
      characteristics, and request of JC program offerings were reported overall, and
      compared between patients requesting the injection center versus those who did
      not. Medication adherence based on the first 6 months of treatment while in the
      program and defined as achieving >=80% proportion of days covered (PDC) was
      measured for patients receiving >=2 paliperidone palmitate injections (n = 2659).
      Logistic models evaluated the association between requests for injection centers
      on medication adherence. RESULTS: Mean age of program enrollees was 40.6
      (standard deviation = 13.9 years), 59.3% were men, and 42.5% were Medicare
      covered. While in the program, 79.9% did not experience a medication gap of >=7
      weeks and 87.0% achieved adherence. Injection center request was associated with
      medication adherence (adjusted odds ratio (aOR) <=5 months: 0.03; 95% confidence
      interval (CI): 0.02-0.05; >=6 months: aOR: 4.16; 95% CI: 2.72-6.36). LIMITATIONS:
      The data sources used were designed for program implementation and not for
      research purposes. CONCLUSIONS: The high percentage of patients requesting
      injection center support and medication shipment in addition to other insurance
      related program offerings signals the need for and value of a comprehensive
      support program for patients seeking LAI therapy. Providing patients with the
      option of alternative and more conveniently located injection centers may help
      them start and maintain their treatment.

PMID- 25978699
TI  - MYD88 expression and L265P mutation in mature B-cell non-Hodgkin lymphomas.
AB  - BACKGROUND: Myeloid differentiation primary response 88 (MYD88) is a common
      adaptor protein that is responsible for signaling from several receptors;
      mutations in this gene may play a role in the pathogenesis of lymphoma. AIM: We
      aimed to determine the MYD88 L265P mutation frequency, the level of MYD88
      expression, and their associations with clinicopathological parameters in mature
      B-cell non-Hodgkin lymphomas (NHLs). METHODS: A total of 68 patients were
      included in the study. The presence of the MYD88 L265P mutation was analyzed by
      real-time polymerase chain reaction and direct sequencing. MYD88 protein
      expression was evaluated by immunohistochemistry (IHC) using two different
      scoring systems. RESULTS: MYD88 L265P mutation was present in eight (18.6%)
      diffuse large B-cell lymphoma (DLBCL) patients. We also observed a significant
      association between the loss of MYD88 expression and advanced stage in both
      mature B-cell NHL and DLBCL according to the first IHC scoring systems (p=0.015
      and p=0.024, respectively). An association was also seen between MYD88
      overexpression and low clinical risk in both mature B-cell NHL and DLBCL
      according to the second IHC scoring system (p=0.027 and p=0.024, respectively).
      CONCLUSIONS: The L265P mutation may be helpful for understanding the pathogenesis
      of immune-privileged site-associated DLBCLs. The presence of the mutation,
      together with its protein overexpression, could also be used as a prognostic
      marker in advanced stage DLBCLs.

PMID- 25978700
TI  - Cation Diffusivity and the Mixed Network Former Effect in Borosilicate Glasses.
AB  - Understanding the structural origins of cationic diffusion processes in silicate
      glasses is important for high-tech applications of silicate glasses. For glasses
      with more than one network former, transport properties such as diffusivity are
      often nonlinear functions of the particular distribution of these network
      formers, a phenomenon known as the mixed network former effect. Here, we
      investigate the sodium-potassium interdiffusion (DNa-K) and the calcium inward
      diffusion (DCa) in soda lime borosilicate glasses with varying silica/borate
      ratio but constant modifier content. Indeed, the structural organization of
      borosilicate glasses results in a pronounced nonlinear composition dependence of
      DNa-K and DCa (i.e., the mixed network former effect). Initial addition of B2O3
      to the glass system results in a significant decrease in both diffusivities,
      whereas the change in diffusivity per mole of added B2O3 decreases with
      increasing B2O3 concentration. Besides the influences of water content and atomic
      packing degree, we find that 99% of the composition dependence of log DNa-K can
      be ascribed to the change in concentration of tetrahedral boron groups. This
      indicates that the formation of BO4/2 groups slows down diffusion processes of
      alkali and alkaline earth ions. Therefore, the mixed network former effect of the
      studied glass series is linked with the change of the concentration of
      tetrahedral boron groups, which is caused by the interactions between the
      different types of network formers. 

PMID- 25978704
TI  - Host response: Sifting out virulent bacteria.

PMID- 25978701
TI  - Long-term PM2.5 Exposure and Neurological Hospital Admissions in the Northeastern
      United States.
AB  - BACKGROUND: Long-term exposure to fine particles (particulate matter <= 2.5 MUm;
      PM2.5) has been consistently linked to heart and lung disease. Recently, there
      has been increased interest in examining the effects of air pollution on the
      nervous system, with evidence showing potentially harmful effects on
      neurodegeneration. OBJECTIVE: Our objective was to assess the potential impact of
      long-term PM2.5 exposure on event time, defined as time to first admission for
      dementia, Alzheimer's (AD), or Parkinson's (PD) diseases in an elderly population
      across the northeastern United States. METHODS: We estimated the effects of PM2.5
      on first hospital admission for dementia, AD, and PD among all Medicare enrollees
      >= 65 years in 50 northeastern U.S. cities (1999-2010). For each outcome, we
      first ran a Cox proportional hazards model for each city, adjusting for prior
      cardiopulmonary-related hospitalizations and year, and stratified by follow-up
      time, age, sex, and race. We then pooled the city-specific estimates by employing
      a random effects meta-regression. RESULTS: We followed approximately 9.8 million
      subjects and observed significant associations of long-term PM2.5 city-wide
      exposure with all three outcomes. Specifically, we estimated a hazard ratio (HR)
      of 1.08 (95% CI: 1.05, 1.11) for dementia, an HR of 1.15 (95% CI: 1.11, 1.19) for
      AD, and an HR of 1.08 (95% CI: 1.04, 1.12) for PD admissions per 1-MUg/m3
      increase in annual PM2.5 concentrations. CONCLUSIONS: To our knowledge, this is
      the first study to examine the relationship between long-term exposure to PM2.5
      and time to first hospitalization for common neurodegenerative diseases. We found
      strong evidence of association for all three outcomes. Our findings provide the
      basis for further studies, as the implications of such exposures could be crucial
      to public health. CITATION: Kioumourtzoglou MA, Schwartz JD, Weisskopf MG, Melly
      SJ, Wang Y, Dominici F, Zanobetti A. 2016. Long-term PM2.5 exposure and
      neurological hospital admissions in the northeastern United States. Environ
      Health Perspect 124:23-29; http://dx.doi.org/10.1289/ehp.1408973.

PMID- 25978705
TI  - There's no place like home.

PMID- 25978709
TI  - Abstracts for the 2015 AACN Scientific Poster Session.

PMID- 25978708
TI  - Achievement of 1020MHz NMR.
AB  - We have successfully developed a 1020MHz (24.0T) NMR magnet, establishing the
      world's highest magnetic field in high resolution NMR superconducting magnets.
      The magnet is a series connection of LTS (low-Tc superconductors NbTi and Nb3Sn)
      outer coils and an HTS (high-Tc superconductor, Bi-2223) innermost coil, being
      operated at superfluid liquid helium temperature such as around 1.8K and in a
      driven-mode by an external DC power supply. The drift of the magnetic field was
      initially +/-0.8ppm/10h without the (2)H lock operation; it was then stabilized
      to be less than 1ppb/10h by using an NMR internal lock operation. The full-width
      at half maximum of a (1)H spectrum taken for 1% CHCl3 in acetone-d6 was as low as
      0.7Hz (0.7ppb), which was sufficient for solution NMR. On the contrary, the
      temporal field stability under the external lock operation for solid-state NMR
      was 170ppb/10h, sufficient for NMR measurements for quadrupolar nuclei such as
      (17)O; a (17)O NMR measurement for labeled tri-peptide clearly demonstrated the
      effect of high magnetic field on solid-state NMR spectra. 

PMID- 25978706
TI  - Secretion systems in Gram-negative bacteria: structural and mechanistic insights.
AB  - Bacteria have evolved a remarkable array of sophisticated nanomachines to export
      various virulence factors across the bacterial cell envelope. In recent years,
      considerable progress has been made towards elucidating the structural and
      molecular mechanisms of the six secretion systems (types I-VI) of Gram-negative
      bacteria, the unique mycobacterial type VII secretion system, the chaperone-usher
      pathway and the curli secretion machinery. These advances have greatly enhanced
      our understanding of the complex mechanisms that these macromolecular structures
      use to deliver proteins and DNA into the extracellular environment or into target
      cells. In this Review, we explore the structural and mechanistic relationships
      between these single- and double-membrane-embedded systems, and we briefly
      discuss how this knowledge can be exploited for the development of new
      antimicrobial strategies. 

PMID- 25978707
TI  - Advances in molecular genetic systems in malaria.
AB  - Robust tools for analysing gene function in Plasmodium parasites, which are the
      causative agents of malaria, are being developed at an accelerating rate. Two
      decades after genetic technologies for use in Plasmodium spp. were first
      described, a range of genetic tools are now available. These include conditional
      systems that can regulate gene expression at the genome, transcriptional or
      protein level, as well as more sophisticated tools for gene editing that use
      piggyBac transposases, integrases, zinc-finger nucleases or the CRISPR-Cas9
      system. In this Review, we discuss the molecular genetic systems that are
      currently available for use in Plasmodium falciparum and Plasmodium berghei, and
      evaluate the advantages and limitations of these tools. We examine the insights
      that have been gained into the function of genes that are important during the
      blood stages of the parasites, which may help to guide the development and
      improvement of drug therapies and vaccines. 

PMID- 25978710
TI  - Adverse radiation effect after stereotactic radiosurgery for brain metastases:
      incidence, time course, and risk factors.
AB  - OBJECT: The authors sought to determine the incidence, time course, and risk
      factors for overall adverse radiation effect (ARE) and symptomatic ARE after
      stereotactic radiosurgery (SRS) for brain metastases. METHODS: All cases of brain
      metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were
      considered. Cases with less than 3 months of follow-up imaging, a gap of more
      than 8 months in imaging during the 1st year, or inadequate imaging availability
      were excluded. Brain scans and pathology reports were reviewed to ensure
      consistent scoring of dates of ARE, treatment failure, or both; in case of
      uncertainty, the cause of lesion worsening was scored as indeterminate.
      Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier
      method with censoring at last imaging. Univariate and multivariate Cox
      proportional hazards analyses were performed. RESULTS: Among 435 patients and
      2200 brain metastases evaluable, the median patient survival time was 17.4 months
      and the median lesion imaging follow-up was 9.9 months. Calculated on the basis
      of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent
      failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%,
      1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were
      symptomatic and 85% occurred 3-18 months after SRS (median 7.2 months). For 99
      ARE cases managed without surgery or bevacizumab, the probabilities of
      improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months
      after onset of ARE. The most important risk factors for ARE included prior SRS to
      the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no
      prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and
      any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy
      volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of
      ARE were < 1%, 1%, 3%, 10%, and 14% for maximum diameter 0.3-0.6 cm, 0.7-1.0 cm,
      1.1-1.5 cm, 1.6-2.0 cm, and 2.1-5.1 cm, respectively. The 1-year probabilities of
      symptomatic ARE leveled off at 13%-14% for brain metastases maximum diameter >
      2.1 cm, target volume > 1.2 cm(3), prescription isodose volume > 1.8 cm(3), 12-Gy
      volume > 3.3 cm(3), and 10-Gy volume > 4.3 cm(3), excluding lesions treated with
      repeat SRS. On both univariate and multivariate analysis, capecitabine, but not
      other systemic therapy within 1 month of SRS, appeared to increase ARE risk. For
      the multivariate analysis considering only metastases with target volume > 1.0
      cm(3), risk factors for ARE included prior SRS, kidney primary tumor, connective
      tissue disorder, and capecitabine. CONCLUSIONS: Although incidence of ARE after
      SRS was low overall, risk increased rapidly with size and volume, leveling off at
      a 1-year cumulative incidence of 13%-14%. This study describes the time course of
      ARE and provides risk estimates by various lesion characteristics and treatment
      parameters to aid in decision-making and patient counseling.

PMID- 25978711
TI  - Complication analysis in nitinol stent-assisted embolization of 486 intracranial
      aneurysms.
AB  - OBJECT: Stent-assisted embolization (SAE) has broadened the scope of endovascular
      cerebral aneurysm treatment. The risks associated with stent selection and
      configuration are poorly defined. In this study, the authors aimed to
      characterize the risk factors that contribute to complications in SAE of
      intracranial aneurysms. METHODS: Over a 10-year period, a single surgeon treated
      486 aneurysms with SAE in which open-cell Neuroform or closed-cell Enterprise
      stents were used. Single stents were used in 386 cases, overlapping stents were
      deployed in 80 cases, and Y-configuration stents were used in the remaining 20
      cases. All neurological complications, which included transient deficits, were
      analyzed; disabling strokes and death were considered major complications. The
      chi-square test and multivariate logistic regression were used to evaluate the
      influence of aneurysm size and morphology, aneurysm location, stent selection,
      and stent configuration on complication rates. RESULTS: There were 7 deaths
      (1.4%), 9 major strokes (1.9%), and 18 minor neurological complications (3.7%).
      For all complications, multivariate analysis revealed that large aneurysm size
      (10-25 mm; p = 0.01), giant aneurysm size (> 25 mm; p = 0.04), fusiform aneurysm
      morphology (p = 0.03), and using a Y-configuration stent (p = 0.048) were
      independent risk factors. For the major complications, independent risk factors
      included an aneurysm in the posterior circulation (p = 0.02), using an
      overlapping stent configuration (p = 0.03), and using a Y-configuration stent (p
      < 0.01). CONCLUSIONS: In this series, SAE for cerebral aneurysm treatment carried
      an acceptable complication rate. With continued innovations in techniques and
      devices and with increased experience, the complication rates associated with SAE
      may be even lower in the future.

PMID- 25978712
TI  - Continuous subcortical motor evoked potential stimulation using the tip of an
      ultrasonic aspirator for the resection of motor eloquent lesions.
AB  - OBJECT: Resection of a motor eloquent lesion has become safer because of
      intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical
      motor evoked potentials (scMEPs) is increasingly used to optimize patient safety.
      So far, scMEP stimulation has been performed intermittently during resection of
      eloquently located lesions. Authors of the present study assessed the possibility
      of using a resection instrument for continuous stimulation of scMEPs. METHODS: An
      ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a
      monopolar subcortical stimulation probe. The effect of the aspirator's use at
      different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation
      intensity was examined in a saline bath. Afterward monopolar stimulation with the
      surgical aspirator was used during the resection of subcortical lesions in the
      vicinity of the corticospinal tract in 14 patients in comparison with scMEP
      stimulation via a standard stimulation electrode. During resection, the
      stimulation current at which an MEP response was still measurable with
      subcortical stimulation using the surgical aspirator was compared with the
      corresponding stimulation current needed using a standard monopolar subcortical
      stimulation probe at the same location. RESULTS: The use of ultrasound at
      different energy levels did result in a slight but irrelevant increase in
      stimulation energy via the tip of the surgical aspirator in the saline bath.
      Stimulation of scMEPs using the surgical aspirator or monopolar probe was
      successful and almost identical in all patients. One patient developed a new
      permanent neurological deficit. Transient new postoperative paresis was observed
      in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14)
      cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14). CONCLUSIONS:
      Continuous motor mapping using subcortical stimulation via a surgical aspirator,
      in comparison with the sequential use of a standard monopolar stimulation probe,
      is a feasible and safe method without any disadvantages. Compared with the
      standard probe, the aspirator offers continuous information on the distance to
      the corticospinal tract.

PMID- 25978713
TI  - Letter to the Editor: Diagnostic strategy in patients with subarachnoid
      hemorrhage.

PMID- 25978714
TI  - A probabilistic map of the human ventral sensorimotor cortex using electrical
      stimulation.
AB  - OBJECT: The human ventral sensorimotor cortex (vSMC) is involved in facial
      expression, mastication, and swallowing, as well as the dynamic and highly
      coordinated movements of human speech production. However, vSMC organization
      remains poorly understood, and previously published population-driven maps of its
      somatotopy do not accurately reflect the variability across individuals in a
      quantitative, probabilistic fashion. The goal of this study was to describe the
      responses to electrical stimulation of the vSMC, generate probabilistic maps of
      function in the vSMC, and quantify the variability across individuals. METHODS:
      Photographic, video, and stereotactic MRI data of intraoperative electrical
      stimulation of the vSMC were collected for 33 patients undergoing awake
      craniotomy. Stimulation sites were converted to a 2D coordinate system based on
      anatomical landmarks. Motor, sensory, and speech stimulation responses were
      reviewed and classified. Probabilistic maps of stimulation responses were
      generated, and spatial variance was quantified. RESULTS: In 33 patients, the
      authors identified 194 motor, 212 sensory, 61 speech-arrest, and 27 mixed
      responses. Responses were complex, stereotyped, and mostly nonphysiological
      movements, involving hand, orofacial, and laryngeal musculature. Within
      individuals, the presence of oral movement representations varied; however, the
      dorsal-ventral order was always preserved. The most robust motor responses were
      jaw (probability 0.85), tongue (0.64), lips (0.58), and throat (0.52).
      Vocalizations were seen in 6 patients (0.18), more dorsally near lip and dorsal
      throat areas. Sensory responses were spatially dispersed; however, patients'
      subjective reports were highly precise in localization within the mouth. The most
      robust responses included tongue (0.82) and lips (0.42). The probability of
      speech arrest was 0.85, highest 15-20 mm anterior to the central sulcus and just
      dorsal to the sylvian fissure, in the anterior precentral gyrus or pars
      opercularis. CONCLUSIONS: The authors report probabilistic maps of function in
      the human vSMC based on intraoperative cortical electrical stimulation. These
      results define the expected range of mapping outcomes in the vSMC of a single
      individual and shed light on the functional organization of the vSMC supporting
      speech motor control and nonspeech functions.

PMID- 25978715
TI  - Falls and peripheral nerve injuries: an age-dependent relationship.
AB  - OBJECT: Despite the growing epidemic of falls, the true incidence of peripheral
      nerve injuries (PNIs) in this patient population remains largely unknown.
      METHODS: The authors performed a retrospective cohort study of 839,210 fall
      injured patients who were registered in the National Trauma Data Bank (NTDB)
      between 2009 and 2011 and fulfilled the inclusion criteria. Regression techniques
      were used to investigate the association of demographic and socioeconomic factors
      with the rate of PNIs in this patient population. The association of age with the
      incidence of PNIs was also investigated. RESULTS: Overall, 3151 fall-injured
      patients (mean age 39.1 years, 33.3% females) sustained a PNI (0.4% of all
      falls). The respective incidence of PNIs was 2.7 per 1000 patients for ground
      level falls, 4.9 per 1000 patients for multilevel falls, and 4.5 per 1000
      patients for falls involving force. This demonstrated a rapid increase in the
      first 2 decades of life, with a maximum rate of 1.1% of all falls in the 3rd
      decade, followed by a slower decline and eventual plateau in the 7th decade. In a
      multivariable analysis, the association of PNIs with age followed a similar
      pattern with patients 20-29 years of age, demonstrating the highest association
      (OR 2.34 [95% CI 2.0-2.74] in comparison with the first decade of life). Falls
      involving force (OR 1.25 [95% CI 1.14-1.37] in comparison with multilevel falls)
      were associated with a higher incidence of PNIs. On the contrary, female sex (OR
      0.87 [95% CI 0.80-0.84]) and ground-level falls (OR 0.79 [95% CI 0.72-0.86]) were
      associated with a lower rate of PNIs. CONCLUSIONS: Utilizing a comprehensive
      national database, the authors demonstrated that PNIs are more common than
      previously described in fall-injured patients and identified their age
      distribution. These injuries are associated with young adults and falls of high
      kinetic energy.

PMID- 25978716
TI  - Misdiagnosis, duration of untreated illness (DUI) and outcome in bipolar patients
      with psychotic symptoms: A naturalistic study.
AB  - BACKGROUND: A number of data show the negative role of duration of untreated
      illness (DUI) on outcome in mood disorders, but no investigation has been carried
      out about the impact of this variable in bipolar disorder (BD) with psychotic
      symptoms. Clinical experience shows that many bipolar patients with psychotic
      symptoms receive other diagnoses and often are chronically treated with first
      generation antipsychotics, with the effect to reduce duration of untreated
      psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose
      of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on
      outcome of bipolar patients with psychotic symptoms. METHOD: Clinical information
      (DUP, DUI, first received diagnosis) about bipolar outpatients with psychotic
      symptoms (N=240) were extrapolated through a retrospective review of the clinical
      charts, Lombardy database and, if necessary, through clinical interviews with
      patients and their relatives. Outcome measures included psychiatric and substance
      abuse comorbidity, occupational status, Global Assessment of Functioning (GAF),
      number of hospitalizations and of suicidal attempts, number of depressive/manic
      recurrences. Patients were divided in two groups according to the DUP (1 year)
      and DUI (8 years) median, and the groups were compared through analyses of
      variance (ANOVAs) for continuous variables or chi(2) tests for dichotomous ones.
      Multivariate analysis of variance (MANOVA) with duration of illness as covariate
      was then performed to eliminate the effect of this variable. Finally, binary
      logistic regressions were performed considering age at onset, DUI, DUP as
      independent variables and outcome variables as dependent ones (presence of
      hospitalizations/suicidal attempts, GAF scores<50, occupational status). RESULTS:
      Most of patients (61.5%) received a first diagnosis different from BD with the
      most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with
      longer DUP were not different in outcome measures with respect to patients with
      shorter DUP. Patients with a DUI >8 years presented higher number of
      hospitalizations (F=6.04, p=0.015), higher number of manic recurrences (F=5.25,
      p=0.023), higher number of depressive recurrences (F=7.13, p=0.008) and lower GAF
      scores (F=17.74, p<0.001). Statistical significance persisted for number of
      hospitalizations (p<0.001) and GAF scores (p=0.003) after MANOVA. Finally binary
      logistic regression showed that a longer DUI was predictive of GAF scores<50
      (F=17.74, p<0.001). DISCUSSION: More than half of bipolar patients with psychotic
      symptoms receive a different diagnosis at first contact with psychiatric
      services. DUI (but not DUP) is a predictor of outcome in bipolar patients with
      psychotic symptoms. This indicates that an early diagnosis and proper treatment
      with a mood stabilizer (or an atypical antipsychotic with mood stabilizing
      effects) may improve long-term outcome of these patients. In the light of the
      naturalistic design of the present paper, these results have to be considered as
      preliminary and have to be confirmed by prospective controlled studies.

PMID- 25978717
TI  - Socioeconomic related inequality in depression among young and middle-adult women
      in Indonesia's major cities.
AB  - PURPOSE: Difficult living conditions in urban areas could result in an increased
      risk of developing depression, particularly among women. One of the strong
      predictors of depression is poverty, which could lead to inequality in risk of
      depression. However, previous studies found conflicting results between poverty
      and depression. This study examines whether depression was unequally distributed
      among young and middle-adult women in Indonesia's major cities and investigate
      the factors contributed to the inequality. METHODS: Data from 1117 young and
      middle-adult women in Indonesia's major cities (Jakarta, Surabaya, Medan, and
      Bandung) were analysed. Concentration Index (CI) was calculated to measure the
      degree of the inequality. The CI was decomposed to investigate the factor
      contributing most to the inequality. RESULTS: The prevalence of depression was
      15% and more concentrated among lower economic group (CI=-0.0545). Compared to
      the middle-adult group, the prevalence of depression among women in the young
      adult group was significantly higher (18% vs 11%, p<0.05) and more equally
      distributed (CI=-0.0343 vs CI=-0.1001). Household consumption expenditure was the
      factor that contributed most to inequality in both group. Other factors
      contributing to inequality were smoking in young-adult group and marital status
      in middle-adult group. Contribution of education to inequality varied for
      different age groups. CONCLUSION: Depression is more concentrated among the lower
      economic groups, with household expenditure being the major factor contributing
      to the inequality. This finding emphasises the importance of primary care level
      mental health services, particularly in poorer urban communities. LIMITATION:
      This study is based on a cross-sectional data, and only assesses social
      determinants of depression. These determinants are important to address in
      addition to biological determinants and other factors.

PMID- 25978718
TI  - Bereavement-related depression: Did the changes induced by DSM-V make a
      difference? Results from a large population-based survey of French residents.
AB  - BACKGROUND: DSM-V has been criticized for excessively expanding criteria for
      bereavement-related depression. The aim of this study was to quantify a potential
      increase in depression prevalence due to changes in diagnostic criteria and to
      assess the severity, clinical profile and healthcare use of new cases. METHODS: A
      cross-sectional telephone survey was performed in 2005-2006 in four French
      regions. Twelve-month prevalence of psychiatric disorders was measured by CIDI
      SF. Bereavement was assessed in those who endorsed the gate question to the
      depression module. Persons with bereavement-related depression according to DSM
      IV and DSM-V diagnosis criteria were compared. RESULTS: Of the 22,138
      respondents, 692 were bereaved. The prevalence of depression among those bereaved
      was 49.9% (95% CI 1/4=43.7-56.0) according to DSM-IV and 59.6% (53.1-66.1)
      according to DSM-V [corrected]. The overall prevalence of major depression
      increased from 8.6% (8.1-9.1) with DSM-IV to 8.8% (8.3-9.3) with DSM-V . Cases
      diagnosed using DSM-IV presented more symptoms than cases diagnosed using DSM-V
      but clinical features were similar except regarding criterion E's symptoms.
      Healthcare use was similar between the two groups regarding consultations and
      psychotropic drug prescription. LIMITATIONS: Some DSM-IV and DSM-V criteria were
      difficult to operationalize in the survey. The observed difference in prevalence
      according to DSM-IV and DSM-V may be reduced when clinical judgment is taken into
      account. CONCLUSIONS: The overall prevalence of major depression is only
      marginally increased by the new criteria. However, diagnostic changes increase
      the prevalence by 10 points among those bereaved. Diagnostic changes do not
      appear to modify service use.

PMID- 25978719
TI  - Anxious, irritable and hostile depression re-appraised.
AB  - BACKGROUND: While classification of the depression disorders currently favors a
      dimensional model, this study considered the empirical support for a spectrum
      model linking personality with phenotypic depressive features, specifically
      examining patients with 'irritable', 'hostile' and 'anxious' depression. METHODS:
      Pearson correlations were performed for Temperament and Personality (T&P) scales
      and state depressive patterns (irritable, hostile and anxious) for patients
      clinically diagnosed with unipolar melancholic and non-melancholic depressive
      conditions. RESULTS: Irritable depression was most strongly associated with T&P
      irritability and anxious depression with T&P anxious-worrying - although these
      associations lacked specificity and were also correlated with other T&P scales.
      Hostile depression was most strongly correlated with T&P irritability suggesting
      that hostile and irritable depression are synonymous patterns. There were no
      clear indications for more distinct associations for the non-melancholic,
      compared to the melancholic, subset. LIMITATIONS: Study findings are limited in
      that measures of state depressive patterns were relatively minimalistic and
      assignment to melancholic and non-melancholic conditions was measured by
      clinician judgment and may be subjective in nature. CONCLUSIONS: Findings offer
      little support in the positioning of anxious and irritable/hostile depression as
      meaningfully differing patterns, nor for the spectrum model being more specific
      to the non-melancholic depressive conditions. There would appear to be little
      utility in preserving these depressive patterns as diagnostic constructs.

PMID- 25978721
TI  - Correction: The Impact of Implementing a Test, Treat and Retain HIV Prevention
      Strategy in Atlanta among Black Men Who Have Sex with Men with a History of
      Incarceration: A Mathematical Model.

PMID- 25978720
TI  - Changes of Adipose Tissue Morphology and Composition during Late Pregnancy and
      Early Lactation in Dairy Cows.
AB  - Dairy cows mobilize large amounts of body fat during early lactation to overcome
      negative energy balance which typically arises in this period. As an adaptation
      process, adipose tissues of cows undergo extensive remodeling during late
      pregnancy and early lactation. The objective of the present study was to
      characterize this remodeling to get a better understanding of adaptation
      processes in adipose tissues, affected by changing metabolic conditions including
      lipid mobilization and refilling as a function of energy status. This was done by
      determining adipocyte size in histological sections of subcutaneous and
      retroperitoneal adipose tissue biopsy samples collected from German Holstein cows
      at 42 days prepartum, and 1, 21, and 100 days postpartum. Characterization of
      cell size changes was extended by the analysis of DNA, triacylglycerol, and
      protein content per gram tissue, and beta-actin protein expression in the same
      samples. In both adipose tissue depots cell size was becoming smaller during the
      course of the study, suggesting a decrease in cellular triacylglycerol content.
      Results of DNA, triacylglycerol, and protein content, and beta-actin protein
      expression could only partially explain the observed differences in cell size.
      The retroperitoneal adipose tissue exhibited a greater extent of time-related
      differences in cell size, DNA, and protein content, suggesting greater dynamics
      and metabolic flexibility for this abdominal depot compared to the investigated
      subcutaneous depot. 

PMID- 25978722
TI  - Can emotions influence level-1 visual perspective taking?
AB  - Emotions and perspective-taking are ubiquitous in our daily social interactions,
      but little is known about the relation between the two. This study examined
      whether and how emotions can influence even the most basic forms of perspective
      taking. Experiment 1 showed that guilt made participants more other-centered in a
      simple visual perspective-taking task while anger tended to make them more self
      centered. These two emotions had, however, no effect on the ability to handle
      conflicting perspectives. Since the guilt induction method used in Experiment 1
      also induced feelings of self-incompetence and shame, Experiment 2 aimed at
      isolating the effects of these concomitant feelings. Self-incompetence/shame
      reduced participants' ability to handle conflicting perspectives but did not
      influence attention allocation. In sum, these results highlight that emotions can
      affect even the simplest form of perspective-taking and that such influence can
      be brought about by the modulation of different cognitive mechanisms.

PMID- 25978723
TI  - Fabrication of Thiol-Ene "Clickable" Copolymer-Brush Nanostructures on Polymeric
      Substrates via Extreme Ultraviolet Interference Lithography.
AB  - We demonstrate a new approach to grafting thiol-reactive nanopatterned copolymer
      brush structures on polymeric substrates by means of extreme ultraviolet (EUV)
      interference lithography. The copolymer brushes were designed to contain
      maleimide functional groups as thiol-reactive centers. Fluoropolymer films were
      exposed to EUV radiation at the X-ray interference lithography beamline (XIL-II)
      at the Swiss Light Source, in order to create radical patterns on their surfaces.
      The radicals served as initiators for the copolymerization of thiol-ene
      "clickable" brushes, composed of a furan-protected maleimide monomer (FuMaMA) and
      different methacrylates, namely, methyl methacrylate (MMA), ethylene glycol
      methyl ether methacrylate (EGMA), or poly(ethylene glycol) methyl ether
      methacrylate (PEGMA). Copolymerization with ethylene-glycol-containing monomers
      provides antibiofouling properties to these surfaces. The number of reactive
      centers on the grafted brush structures can be tailored by varying the monomer
      ratios in the feed. Grafted copolymers were characterized by using attenuated
      total reflection infrared (ATR-IR) spectroscopy. The reactive maleimide
      methacrylate (MaMA) units were utilized to conjugate thiol-containing moieties
      using the nucleophilic Michael-addition reaction, which proceeds at room
      temperature without the need for any metal-based catalyst. Using this approach, a
      variety of functionalities was introduced to yield polyelectrolytes, as well as
      fluorescent and light-responsive polymer-brush structures. Functionalization of
      the brush structures was demonstrated via ATR-IR and UV-vis spectroscopy and
      fluorescence microscopy, and was also indicated by a color switch. Furthermore,
      grafted surfaces were generated via plasma activation, showing a strongly
      increased wettability for polyelectrolytes and a reversible switch in static
      water contact angle (CA) of up to 18 degrees  for P(EGMA-co-MaMA-SP) brushes,
      upon exposure to alternating visible and UV-light irradiation. 

PMID- 25978724
TI  - Endoplasmic reticulum stress impairs insulin receptor signaling in the brains of
      obese rats.
AB  - The incidence of obesity is increasing worldwide. It was reported that
      endoplasmic reticulum stress (ERS) could inhibit insulin receptor signaling by
      activating c-Jun N-terminal kinase (JNK) in the liver. However, the relationship
      between ERS and insulin receptor signaling in the brain during obesity remains
      unclear. The aim of the current study was to assess whether ERS alters insulin
      receptor signaling through the hyper-activation of JNK in the hippocampus and
      frontal cortex in the brains of obese rats. Obesity was induced using a high fat
      diet (HFD). The Morris water maze test was then performed to evaluate decreases
      in cognitive function, and western blot was used to verify whether abnormal
      insulin receptor signaling was induced by ERS in HFD rats exhibiting cognitive
      decline. In addition, to determine whether ERS activated JNK and consequently
      impaired insulin receptor signaling, SH-SY5Y cells were treated with the JNK
      inhibitor, SP600125, followed by tunicamycin or thapsigargin, and primary rat
      hippocampal and cortical neurons were transfected with siRNA against IRE1alpha
      and JNK. We found that the expression of phosphorylation of PKR-like kinase
      (PERK), phosphorylation of alpha subunit of translation initiation factor 2
      (eIF2alpha), and phosphorylation of inositol-requiring kinase-1alpha (IRE-1alpha)
      were increased in the brains of rats with HFD when compared with control rats.
      The level of serine phosphorylation of insulin receptor substrate-1 (IRS-1) was
      also increased, while protein kinase B (PKB/Akt) was reduced. ERS was also found
      to inhibit insulin receptor signaling via the activation of JNK in SH-SY5Y cells,
      primary rat hippocampal, and cortical neurons. These results indicate that ERS
      was increased, thereby resulting in impaired insulin receptor signaling in the
      hippocampus and frontal cortex of obese rats. 

PMID- 25978726
TI  - Rhodobacter sphaeroides mutants overexpressing chlorophyllide a oxidoreductase of
      Blastochloris viridis elucidate functions of enzymes in late bacteriochlorophyll
      biosynthetic pathways.
AB  - In previous studies we have demonstrated that chlorophyllide a oxidoreductases
      (CORs) from bacteriochlorophyll (BChl) a-producing Rhodobacter species and BChl b
      producing Blastochloris viridis show distinct substrate recognition and different
      catalytic hydrogenation reactions, and that these two types of CORs therefore
      cause committed steps for BChls a and b biosynthesis. In this study, COR genes
      from B. viridis were incorporated and overexpressed in a series of Rhodobacter
      sphaeroides mutants. We found that the following two factors are essential in
      making R. sphaeroides produce BChl b: the loss of functions of both intrinsic COR
      and 8-vinyl reductase (BciA) in the host R. sphaeroides strain; and expression of
      the BchYZ catalytic components of COR from B. viridis, not the complete set of
      COR (BchXYZ), in the host strain. In addition, we incorporated bchYZ of B.
      viridis into the R. sphaeroides mutant lacking BchJ and BciA, resulting in the
      strain accumulating both BChl a and BChl b. This is the first example of an
      anoxygenic photosynthetic bacterium producing BChls a and b together. The results
      suggest that BchJ enhances activity of the intrinsic COR. The physiological
      significance of BchJ in pigment biosynthetic pathways will be discussed.

PMID- 25978725
TI  - Mfn2 Affects Embryo Development via Mitochondrial Dysfunction and Apoptosis.
AB  - BACKGROUND: Growth factors, energy sources, and mitochondrial function strongly
      affect embryo growth and development in vitro. The biological role and
      prospective significance of the mitofusin gene Mfn2 in the development of
      preimplantation embryos remain poorly understood. Our goal is to profile the role
      of Mfn2 in mouse embryos and determine the underlying mechanism of Mfn2 function
      in embryo development. METHODS: We transfected Mfn2-siRNA into 2-cell fertilized
      eggs and then examined the expression of Mfn2, the anti-apoptotic protein Bcl-2,
      and the apoptosis-promoting protein Bax by Western blot. Additionally, we
      determined the blastocyst formation rate and measured ATP levels, mtDNA levels,
      mitochondrial membrane potential (DeltaPsim), and apoptosis in all of the
      embryos. RESULTS: The results indicate that the Mfn2 and Bcl-2 levels were
      markedly decreased, whereas Bax levels were increased in the T group (embryos
      transfected with Mfn2-siRNA) compared with the C group (embryos transfected with
      control-siRNA). The blastocyst formation rate was significantly decreased in the
      T group. The ATP content and the relative amounts of mtDNA and cDNA in the T
      group were significantly reduced compared with the C group. In the T group,
      DeltaPsim and Ca(2+) levels were reduced, and the number of apoptotic cells was
      increased. CONCLUSION: Low in vitro expression of Mfn2 attenuates the blastocyst
      formation rate and cleavage speed in mouse zygotes and causes mitochondrial
      dysfunction, as confirmed by the ATP and mtDNA levels and mitochondrial membrane
      potential. Mfn2 deficiency induced apoptosis through the Bcl-2/Bax and Ca(2+)
      pathways. These findings indicate that Mfn2 could affect preimplantation embryo
      development through mitochondrial function and cellular apoptosis.

PMID- 25978727
TI  - A ranking-based meta-analysis reveals let-7 family as a meta-signature for grade
      classification in breast cancer.
AB  - Breast cancer is one of the most important causes of cancer-related deaths
      worldwide in women. In addition to gene expression studies, the progressing work
      in the miRNA area including miRNA microarray studies, brings new aspects to the
      research on the cancer development and progression. Microarray technology has
      been widely used to find new biomarkers in research and many transcriptomic
      microarray studies are available in public databases. In this study, the breast
      cancer miRNA and mRNA microarray studies were collected according to the
      availability of their data and clinical information, and combined by a newly
      developed ranking-based meta-analysis approach to find out candidate miRNA
      biomarkers (meta-miRNAs) that classify breast cancers according to their grades
      and explain the relation between miRNAs and mRNAs. This approach provided meta
      miRNAs specific to breast cancer grades, pointing out let-7 family members as
      grade classifiers. The qRT-PCR studies performed with independent breast tumors
      confirmed the potential biomarker role of let-7 family members (meta-miRNAs). The
      concordance between the meta-mRNAs and miRNA target genes specific to tumor grade
      (common genes) supported the idea of mRNAs as miRNA targets. The pathway analysis
      results showed that most of the let-7 family miRNA targets, and also common
      genes, were significantly taking part in cancer-related pathways. The qRT-PCR
      studies, together with bioinformatic analyses, confirmed the results of meta
      analysis approach, which is dynamic and allows combining datasets from different
      platforms. 

PMID- 25978728
TI  - CLINICAL CHARACTERISTICS AND TREATMENT OUTCOMES OF COATS DISEASE IN A SAUDI
      ARABIAN POPULATION.
AB  - PURPOSE: To present the clinical aspects and treatment outcomes of Coats disease
      in Saudi Arabia. METHODS: A retrospective chart review was performed of 92
      patients (97 eyes) diagnosed with Coats disease at King Khalid Eye Specialist
      Hospital from 1983 to 2010. RESULTS: The most common presenting complaint was
      decreased visual acuity followed by strabismus and then leukocoria. Snellen
      visual acuity was 20/20 to 20/50 in 9 eyes (9%), 20/50 to 20/160 in 11 eyes
      (11%), 20/200-counting fingers in 29 eyes (30%), and hand motion to no light
      perception in 24 eyes (25%). Telangiectasia was located in the preequatorial area
      in 71 eyes (73%) and most commonly involved the temporal retina in 67 eyes (69%).
      In eyes with clear view to the fundus, quadrant involvement by telangiectasia had
      the following distribution: 1) quadrant (n = 36, 37%); 2) quadrants (n = 26,
      27%); 3) quadrants (n = 8, 8%); and 4 quadrants (n = 15, 15%). Total retinal
      detachment was present at presentation in 28 eyes (29%) and neovascular glaucoma
      in 8 (8%). Based on the Shields classification, the eyes were Stage 1 (n = 1,
      1%), Stage 2A (n = 7, 7%), Stage 2B (n = 23, 24%), Stage 3A1 (n = 26, 27%), Stage
      3A2 (n = 12, 12%), Stage 3B (n = 16, 17%), Stage 4 (n = 11, 11%), and Stage 5 (n
      = 5, 1%). Stage 3A was the most commonly presented stage (39%). Primary
      management included cryotherapy (19%), laser photocoagulation (64%), intravitreal
      agents (9%), and surgical drainage (4%). Combination treatment was performed in
      29% of eyes. Thirteen eyes (13%) were enucleated because of clinical suspicion of
      retinoblastoma or the presence of glaucoma. Factors that were associated with a
      poor visual outcome of 20/200 or worse included age less than 10 years (relative
      risk: 1.27), Stages 3 and 4 disease (relative risk: 1.40), presence of subretinal
      fluid in all 4 quadrants including the fovea (relative risk: 14.25), and initial
      visual acuity of 20/200 (relative risk: 6.72) or worse (P < 0.005 for all
      factors). CONCLUSION: Although rare, Coats disease is usually advanced at
      presentation and has a poor visual prognosis in the Saudi population, like in
      other populations. The findings of this study give validity and applicability to
      the Shields staging scheme, which we recommend using in clinical practice.

PMID- 25978729
TI  - INNER NUCLEAR LAYER THICKNESS AS A PROGNOSTIC FACTOR FOR METAMORPHOPSIA AFTER
      EPIRETINAL MEMBRANE SURGERY.
AB  - PURPOSE: To evaluate prognostic factors for metamorphopsia in patients undergoing
      vitrectomy for epiretinal membrane using spectral domain optical coherence
      tomography. METHODS: This study included 53 eyes of 53 patients undergoing
      vitrectomy for idiopathic epiretinal membrane. The authors examined visual
      acuity, severity of metamorphopsia with M-CHARTS, and retinal microstructures
      with spectral domain optical coherence tomography before surgery and 3 months and
      6 months after surgery. Central foveal thickness, parafoveal retinal thickness,
      macular volume, thickness of the ganglion cell layer, inner nuclear layer, and
      outer retinal layer (ONL + OPL: outer nuclear layer and outer plexiform layer)
      were analyzed using an image processing program. The status of the outer retinal
      lines was also evaluated. RESULTS: Preoperative metamorphopsia score (M-score)
      significantly correlated with central foveal thickness, inner nuclear layer
      thickness, and ONL + OPL thickness. Postoperative M-score significantly
      correlated with postoperative central foveal thickness and inner nuclear layer
      thickness. Inner nuclear layer thickness had significant correlation with M-score
      at each time point by multiple regression analysis, whereas other parameters were
      not relevant. Multiple regression analysis showed that preoperative inner nuclear
      layer thickness yielded the highest regression coefficient with postoperative M
      score. CONCLUSION: Inner nuclear layer thickness was found to be a good indicator
      of metamorphopsia both before and after surgery and a predictor of postoperative
      metamorphopsia in patients with epiretinal membrane.

PMID- 25978730
TI  - UTILIZATION OF FUNDUS AUTOFLUORESCENCE, SPECTRAL DOMAIN OPTICAL COHERENCE
      TOMOGRAPHY, AND ENHANCED DEPTH IMAGING IN THE CHARACTERIZATION OF BIETTI
      CRYSTALLINE DYSTROPHY IN DIFFERENT STAGES.
AB  - PURPOSE: To characterize Bietti crystalline dystrophy (BCD) in different stages
      using multiple imaging modalities. METHODS: Sixteen participants clinically
      diagnosed as BCD were included in the retrospective study and were categorized
      into 3 stages according to fundus photography. Eleven patients were genetically
      confirmed. Fundus autofluorescence, spectral domain optical coherence tomography,
      and enhanced depth imaging features of BCD were analyzed. RESULTS: On fundus
      autofluorescence, the abnormal autofluorescence was shown to enlarge in area and
      decrease in intensity with stages. Using spectral domain optical coherence
      tomography, the abnormalities in Stage 1 were observed to localize in outer
      retinal layers, whereas in Stage 2 and Stage 3, more extensive retinal atrophy
      was seen. In enhanced depth imaging, the subfoveal choroidal layers were
      delineated clearly in Stage 1; in Stage 2, destructions were primarily found in
      the choriocapillaris with associated alterations in the outer vessels; Stage 3
      BCD displayed severe choroidal thinning. Choroidal neovascularization and macular
      edema were exhibited with high incidence. IVS6-8del17bp/inGC of the CYP4V2 gene
      was the most common mutant allele. CONCLUSION: Noninvasive fundus
      autofluorescence, spectral domain optical coherence tomography, and enhanced
      depth imaging may help to characterize the chorioretinal pathology of BCD at
      different degrees, and therefore, we propose staging of BCD depending on those
      methods. Physicians should be cautious of the vision-threatening complications of
      the disease.

PMID- 25978731
TI  - COMPARISON OF SURGICAL OUTCOME OF 23-GAUGE AND 25-GAUGE MICROINCISION VITRECTOMY
      SURGERY FOR MANAGEMENT OF IDIOPATHIC EPIRETINAL MEMBRANE IN PSEUDOPHAKIC EYES.
AB  - PURPOSE: To compare the visual outcomes and occurrences of postoperative
      complications after 23-gauge (G) and 25-G microincision vitrectomy surgery (MIVS)
      for idiopathic epiretinal membrane in pseudophakic eyes. METHODS: A total of 239
      pseudophakic eyes of 239 patients who underwent 23-G (n = 159) or 25-G MIVS (n =
      80) for removal of idiopathic epiretinal membrane between March 2010 and March
      2013 were included in this retrospective study. Patients were followed up on
      postoperative 1 day, 1 week, 1, 3, and 6 months. Postoperative visual acuity,
      intraocular pressure, and intraoperative or postoperative complications were
      compared between the 23-G and 25-G MIVS groups. RESULTS: Both groups showed a
      statistically significant improvement in best-corrected visual acuity at
      postoperative 1, 3, and 6 months (All P < 0.05). Furthermore, the mean change of
      best-corrected visual acuity was not significantly different between the 2 groups
      at postoperative 1, 3, and 6 months (P = 0.208, P = 0.547, and P = 0.519,
      respectively), but 25-G MIVS group showed faster visual recovery than 23-G MIVS
      group at postoperative 1 day and at 1 week (P = 0.015, and P < 0.001,
      respectively). Severe hypotony of intraocular pressure less than 6 mmHg (3 eyes,
      1.9%) or intraocular pressure elevation over 30 mmHg at postoperative 1 day (3
      eyes, 1.9%) was found in the 23-G group, but not in the 25-G group, and was not
      statistically different between the groups (P = 0.553). More eyes required
      intraoperative suturing of sclerotomy sites in the 23-G group (18 eyes, 11.3%),
      whereas none of the eyes in the 25-G group needed suturing of sclerotomy (P <
      0.002). CONCLUSION: Both 23-G and 25-G MIVS yielded comparable visual outcomes
      for surgical treatment of idiopathic epiretinal membrane in pseudophakic eyes.
      The 25-G MIVS was associated with faster visual recovery and less postoperative
      hypotony than 23-G surgery.

PMID- 25978732
TI  - NOCARDIA CHOROIDAL ABSCESS: Risk Factors, Treatment Strategies, and Visual
      Outcomes.
AB  - PURPOSE: To describe the risk factors, clinical course, ancillary test findings,
      treatment strategies, and visual outcomes of a series of patients with choroidal
      abscesses caused by endogenous Nocardia. METHODS: This retrospective, consecutive
      noncomparative case series included all patients with Nocardia ocular infections
      at 3 tertiary medical centers over the past 20 years. RESULTS: Five eyes in 5
      patients were identified with choroidal abscesses because of Nocardia. All
      patients were immunocompromised: one suffered from AIDS and four had autoimmune
      disorders. Three of the 5 patients (60%) underwent systemic evaluation, and in
      all 3, nonocular nocardiosis was identified. Four patients (80%) underwent
      diagnostic ophthalmic surgery and received systemic and intravitreal antibiotics.
      The final patient deferred these interventions. Outcomes at the last follow-up
      examination were 20/25, 1/200, hand motion at 1 foot, and 2 patients underwent
      enucleation. Mean follow-up (+/- standard deviation) was 159 (+/- 103) days.
      CONCLUSION: Immunosuppression is the most significant risk factor for developing
      Nocardia choroidal abscesses. Definitive diagnosis generally requires subretinal
      biopsy, which is also critical to implementing appropriate antibiotic therapy.

PMID- 25978733
TI  - INTRASURGICAL MICROSCOPE-INTEGRATED SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY
      ASSISTED MEMBRANE PEELING.
AB  - PURPOSE: To evaluate microscope-integrated intrasurgical spectral domain optical
      coherence tomography during macular surgery in a prospective monocenter study.
      METHODS: Before pars plana vitrectomy and before, during, and after membrane
      peeling, 512 * 128 macular cube scans were performed using a Carl Zeiss Meditec
      Cirrus high-definition OCT system adapted to the optical pathway of a Zeiss OPMI
      VISU 200 surgical microscope and compared with retinal staining. RESULTS: The
      study included 51 patients with epiretinal membranes, with 8 of those having
      additional lamellar macular holes, 11 patients with vitreomacular traction, and 8
      patients with full-thickness macular holes. Intraoperative spectral domain
      optical coherence tomography allowed performing membrane peeling without using
      retinal dyes in 40% of cases (28 of 70 patients). No residual membranes were
      found in 94.3% of patients (66 of 70 patients) in intrasurgical spectral domain
      optical coherence tomography and subsequent (re)staining. In patients with
      vitreomacular traction, intrasurgical spectral domain optical coherence
      tomography scans facilitated decisions on the need for an intraocular tamponade
      after membrane peeling. CONCLUSION: Intraoperative spectral domain optical
      coherence tomography was comparable with retinal dyes in confirming success after
      membrane peeling. However, the visualization of flat membranes was better after
      staining.

PMID- 25978734
TI  - Nanoplate-Built ZnO Hollow Microspheres Decorated with Gold Nanoparticles and
      Their Enhanced Photocatalytic and Gas-Sensing Properties.
AB  - Hierarchical porous ZnO microspheres decorated with gold nanoparticles (AuNPs)
      were successfully synthesized by a facile solvothermal route. The hierarchical
      ZnO superstructure was constructed of interconnected nanoplates with numerous
      voids. Photoluminescence, X-ray photoelectron spectroscopy, and electron
      paramagnetic resonance measurements demonstrated that the main defects were
      oxygen vacancies (V(O)(*)) with minor interstitial oxygen (O(i)(-)) in the
      hierarchical ZnO hollow microspheres. The as-prepared hierarchical ZnO hollow
      microspheres and the AuNPs used to decorate them were examined for their
      photocatalytic degradation ability and as gas sensors. The photodegradation
      results demonstrated that the degradation rate constant on rhodamine B for
      undecorated ZnO microspheres was 0.43 min(-1), which increased to 1.76 min(-1)
      for AuNP-decorated ZnO microspheres. The AuNP-functionalized ZnO microspheres
      displayed superior sensing properties, with a 3-fold enhancement in their gas
      response to 1 ppb of dibutyl phthalate.

PMID- 25978735
TI  - Expression and Anthocyanin Biosynthesis-Modulating Potential of Sweet Cherry
      (Prunus avium L.) MYB10 and bHLH Genes.
AB  - Anthocyanins are essential contributors to fruit coloration, an important quality
      feature and a breed determining trait of a sweet cherry fruit. It is well
      established that the biosynthesis of anthocyanins is regulated by an interplay of
      specific transcription factors belonging to MYB and bHLH families accompanied by
      a WD40 protein. In this study, we isolated and analyzed PaWD40, PabHLH3,
      PabHLH33, and several closely related MYB10 gene variants from different
      cultivars of sweet cherry, analyzed their expression in fruits with different
      anthocyanin levels at several developmental stages, and determined their
      capabilities to modulate anthocyanin synthesis in leaves of two Nicotiana
      species. Our results indicate that transcription level of variant PaMYB10.1-1
      correlates with fruit coloration, but anthocyanin synthesis in Nicotiana was
      induced by another variant, PaMYB10.1-3, which is moderately expressed in fruits.
      The analysis of two fruit-expressed bHLH genes revealed that PabHLH3 enhances MYB
      induced anthocyanin synthesis, whereas PabHLH33 has strong inhibitory properties.

PMID- 25978736
TI  - Spontaneous magnetic alignment by yearling snapping turtles: rapid association of
      radio frequency dependent pattern of magnetic input with novel surroundings.
AB  - We investigated spontaneous magnetic alignment (SMA) by juvenile snapping turtles
      using exposure to low-level radio frequency (RF) fields at the Larmor frequency
      to help characterize the underlying sensory mechanism. Turtles, first introduced
      to the testing environment without the presence of RF aligned consistently
      towards magnetic north when subsequent magnetic testing conditions were also free
      of RF ('RF off -> RF off'), but were disoriented when subsequently exposed to RF
      ('RF off -> RF on'). In contrast, animals initially introduced to the testing
      environment with RF present were disoriented when tested without RF ('RF on -> RF
      off'), but aligned towards magnetic south when tested with RF ('RF on -> RF on').
      Sensitivity of the SMA response of yearling turtles to RF is consistent with the
      involvement of a radical pair mechanism. Furthermore, the effect of RF appears to
      result from a change in the pattern of magnetic input, rather than elimination of
      magnetic input altogether, as proposed to explain similar effects in other
      systems/organisms. The findings show that turtles first exposed to a novel
      environment form a lasting association between the pattern of magnetic input and
      their surroundings. However, under natural conditions turtles would never
      experience a change in the pattern of magnetic input. Therefore, if turtles form
      a similar association of magnetic cues with the surroundings each time they
      encounter unfamiliar habitat, as seems likely, the same pattern of magnetic input
      would be associated with multiple sites/localities. This would be expected from a
      sensory input that functions as a global reference frame, helping to place
      multiple locales (i.e., multiple local landmark arrays) into register to form a
      global map of familiar space. 

PMID- 25978737
TI  - Identification of highly reactive cysteine residues at less exposed positions in
      the Fab constant region for site-specific conjugation.
AB  - Engineered cysteine residues are currently used for the site-specific conjugation
      of antibody-drug conjugates (ADC). In general, positions on the protein surface
      have been selected for substituting a cysteine as a conjugation site; however,
      less exposed positions (with less than 20% of accessible surface area [ASA]) have
      not yet been evaluated. In this study, we engineered original cysteine positional
      variants of a Fab fragment, with less than 20% of ASA, and evaluated their thiol
      reactivities through conjugation with various kinds of payloads. As a result, we
      have identified three original cysteine positional variants (heavy chain: Hc
      A140C, light chain: Lc-Q124C and Lc-L201C), which exhibited similar monomer
      content, thermal stability, and antigen binding affinity in comparison to the
      wild-type Fab. In addition, the presence of cysteine in these positions made it
      possible for the Fab variants to react with variable-sized molecules with high
      efficiency. The favorable physical properties of the cysteine positional variants
      selected in our study suggest that less exposed positions, with less than 20% of
      ASA, provide an alternative for creating conjugation sites. 

PMID- 25978739
TI  - From the Editor-in-Chief's Desk.

PMID- 25978738
TI  - Obesity, metabolic syndrome and risk of atrial fibrillation: a Swedish,
      prospective cohort study.
AB  - AIM: We aimed to investigate whether different measures of obesity could
      similarly predict atrial fibrillation, and whether the atrial fibrillation risk
      associated with obesity is dependent on presence of metabolic syndrome. MATERIAL
      AND METHODS: We performed our study in a population-based longitudinal
      cardiovascular study, comprising 1 924 men and 2 097 women, aged 60 years, from
      Stockholm. Body mass index, waist circumference, sagittal abdominal diameter and
      components of metabolic syndrome (systolic- and diastolic blood pressure, fasting
      glucose, triglycerides, high-density lipoprotein-cholesterol) were recorded at
      baseline. Participants were classified by their body mass index (normal weight,
      overweight or obese), waist circumference (normal, semi-elevated or elevated),
      and according to presence of metabolic syndrome. Atrial fibrillation risk was
      estimated by Cox proportional hazards regression models, adjusted for common
      atrial fibrillation risk factors, expressed as HR and 95% CI. RESULTS: During a
      mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were
      recorded. One standard deviation increment of each obesity measure was associated
      with increased atrial fibrillation risk as: body mass index 1.25 (1.12 - 1.40),
      waist circumference 1.35 (1.19 - 1.54) and sagittal abdominal diameter 1.28 (1.14
      - 1.44). Compared to normal weight subjects without metabolic syndrome, increased
      atrial fibrillation risk was noted for overweight subjects with metabolic
      syndrome, 1.67 (1.16 - 2.41), obese subjects without metabolic syndrome, 1.75
      (1.11 - 2.74) and obese subjects with metabolic syndrome, 1.92 (1.34 - 2.74).
      Compared to subjects with normal waist circumference without metabolic syndrome,
      subjects with elevated waist circumference and metabolic syndrome suffered
      increased atrial fibrillation risk, 2.03 (1.44 - 2.87). CONCLUSIONS: Body mass
      index, waist circumference and sagittal abdominal diameter could similarly
      predict atrial fibrillation. Obesity was associated with an increased atrial
      fibrillation risk regardless of metabolic syndrome, whereas overweight and
      elevated waist circumference was associated with increased atrial fibrillation
      risk only if metabolic syndrome was present.

PMID- 25978740
TI  - Assessing change in core autism symptoms: challenges for pharmacological studies.

PMID- 25978741
TI  - Acute and longer-term safety results from a pooled analysis of duloxetine studies
      for the treatment of children and adolescents with major depressive disorder.
AB  - OBJECTIVE: To assess acute and longer-term safety of duloxetine in the treatment
      of children and adolescents with major depressive disorder (MDD), a pooled
      analysis of data from two completed randomized, double-blind, multicenter, phase
      3, placebo- and active-controlled trials was undertaken. In these studies,
      neither duloxetine (investigational drug) nor fluoxetine (active control)
      demonstrated a statistically significant improvement compared with placebo on the
      primary efficacy measure. METHODS: Patients ages 7-17 years with MDD as defined
      by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text
      Revision (DSM-IV-TR) received duloxetine (n=341), fluoxetine (n=234), or placebo
      (n=225) for 10 week acute and 26 week extended (duloxetine or fluoxetine only)
      treatments. Safety measures included treatment-emergent adverse events (TEAEs),
      the Columbia-Suicide Severity Rating Scale, vital signs, electrocardiograms,
      laboratory samples, and growth (height and weight) assessments. RESULTS:
      Significantly more patients discontinued because of adverse events during
      duloxetine (8.2%) treatment than during placebo (3.1%) treatment (p<=0.05). TEAEs
      in >10% of duloxetine-treated patients were headache and nausea. No completed
      suicides or deaths occurred. During acute treatment, 6.6% of duloxetine-, 8.0% of
      fluoxetine-, and 8.2% of placebo-treated patients had worsening suicidal ideation
      from baseline. Among patients initially randomized to duloxetine or fluoxetine
      who had suicidal ideation at study baseline, 81% of duloxetine- and 77% of
      fluoxetine-treated patients had improvements in suicidal ideation at end-point in
      the 36-week studies. Suicidal behavior occurred in two fluoxetine-treated
      patients and one placebo-treated patient during acute treatment, and in seven
      duloxetine-treated patients and one fluoxetine-treated patient during extended
      treatment. Duloxetine-treated patients had a mean pulse increase of ~3 beats per
      minute, and mean blood pressure (both systolic and diastolic) increases of <2.0
      mm Hg at week 36. Weight decrease (>=3.5%) during acute treatment occurred with
      statistically (p<=0.05) greater frequency for both the duloxetine (11.4%) and
      fluoxetine (11.5%) groups versus the placebo (5.5%) group; however, mean weight
      increase occurred for both duloxetine and fluoxetine groups during extended
      treatment. CONCLUSION: Results from this pooled analysis of two studies were
      consistent with the known safety and tolerability profile of duloxetine. Clinical
      Trial Registry Numbers: NCT00849901 and NCT00849693.

PMID- 25978742
TI  - Placebo-controlled trial of valproic Acid versus risperidone in children 3-7
      years of age with bipolar I disorder.
AB  - OBJECTIVE: The objective of this study was to determine the efficacy and safety
      of valproic acid versus risperidone in children, 3-7 years of age, with bipolar I
      disorder (BPD), during a mixed or manic episode. METHODS: Forty-six children with
      Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision
      (DSM-IV-TR) diagnosis of bipolar disorder, manic, hypomanic, or mixed episode,
      were recruited over a 6 year period from two academic outpatient programs for a
      double-blinded, placebo-controlled trial in which subjects were randomized in a
      2:2:1 ratio to risperidone solution, valproic acid, or placebo. RESULTS: After 6
      weeks of treatment, the least-mean Young Mania Rating Scale (YMRS) total scores
      change, adjusted for baseline YMRS scores, from baseline by treatment group was:
      Valproic acid 10.0+/-2.46 (p=0.50); risperidone 18.82+/-1.55 (p=0.008); and
      placebo 4.29+/-3.56 (F=3.93, p=0.02). The mixed models for repeated measure
      (MMRM) analysis found a significant difference for risperidone-treated subjects
      versus placebo treated subjects (p=0.008) but not for valproic acid-treated
      subjects versus placebo-treated subjects (p=0.50). Treatment with risperidone
      over 6 weeks led to increased prolactin levels, liver functions, metabolic
      measures, and weight/body mass index (BMI). Treatment with valproic acid led to
      increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin,
      and hematocrit. CONCLUSIONS: In this small sample of preschool children with BPD,
      risperidone demonstrated clear efficacy versus placebo, whereas valproic acid did
      not. The laboratory and weight findings suggest that younger children with BPD
      are more sensitive to the effects of both of these psychotropics, and that,
      therefore, frequent laboratory and weight monitoring are warranted.

PMID- 25978743
TI  - A pilot trial of cognitive-behavioral therapy augmentation of antibiotic
      treatment in youth with pediatric acute-onset neuropsychiatric syndrome-related
      obsessive-compulsive disorder.
AB  - BACKGROUND: This study reports an open trial of family-based cognitive-behavioral
      therapy (CBT) in children and adolescents with obsessive-compulsive disorder
      (OCD) exhibiting an onset pattern consistent with pediatric acute-onset
      neuropsychiatric syndrome (PANS). METHODS: Eleven primarily Caucasian youth with
      PANS-related OCD (range=4-14 years; 6 boys) who were incomplete responders to
      antibiotic treatment, received family-based CBT delivered either face-to-face or
      via web camera. RESULTS: All participants completing treatment (8 of 8) were
      considered improved at posttreatment, and average obsessive-compulsive symptom
      severity was reduced by 49%. Significant reductions in obsessive-compulsive
      symptom severity and in clinician- and parent-rated OCD-related impairment were
      noted. Reductions in parent- and child-rated anxiety, child-rated OCD-related
      impairment, and comorbid neuropsychiatric symptoms were not statistically
      significant. CONCLUSIONS: Gains were maintained at follow-up, with 100% (6 of 6)
      of those assessed remaining improved. Implications for treatment and further
      research are discussed.

PMID- 25978744
TI  - Neuroleptic Malignant Syndrome in a Boy with NMDA Receptor Encephalitis.

PMID- 25978746
TI  - Randomized controlled trial of heart rate variability biofeedback in cardiac
      autonomic and hostility among patients with coronary artery disease.
AB  - Hostility is a psychosocial risk factor that may decrease heart rate variability
      (HRV) in coronary artery disease (CAD) through cardiac autonomic imbalance. Heart
      rate variability biofeedback (HRV-BF) increases HRV indices and baroreflex gain.
      This study examines the effectiveness of HRV-BF in restoring cardiac autonomic
      balance and decreasing hostility among patients with CAD. One hundred and fifty
      four patients with CAD were assigned randomly to receive 6 weeks of HRV-BF, in
      addition to the standard medical care received by the wait-list control (WLC)
      group. A 5-min electrocardiogram, blood pressure, and hostility were assessed pre
      intervention, post-intervention, and at 1-month follow-up. The standard deviation
      of normal-to-normal intervals (SDNN), low frequency (LF), and log LF at post
      intervention was significantly higher than that at pre-intervention in the HRV-BF
      group. Baseline log LF was significantly higher post-intervention and at follow
      up after HRV-BF training than at pre-intervention. The treatment curve of log LF
      pre-session increased significantly after session 2, which was maintained to post
      intervention. Expressive hostility, suppressive hostility, and hostility total
      score at post-intervention and one-month follow-up after HRV-BF were
      significantly lower than at pre-intervention. This study showed increased HRV and
      decreased expressive and suppressive hostility behavior in patients with CAD
      following HRV-BF. 

PMID- 25978745
TI  - A Kazal-Type Serine Protease Inhibitor from the Defense Gland Secretion of the
      Subterranean Termite Coptotermes formosanus Shiraki.
AB  - Coptotermes formosanus is an imported, subterranean termite species with the
      largest economic impact in the United States. The frontal glands of the soldier
      caste termites comprising one third of the body mass, contain a secretion
      expelled through a foramen in defense. The small molecule composition of the
      frontal gland secretion is well-characterized, but the proteins remain to be
      identified. Herein is reported the structure and function of one of several
      proteins found in the termite defense gland secretion. TFP4 is a 6.9 kDa, non
      classical group 1 Kazal-type serine protease inhibitor with activity towards
      chymotrypsin and elastase, but not trypsin. The 3-dimensional solution structure
      of TFP4 was solved with nuclear magnetic resonance spectroscopy, and represents
      the first structure from the taxonomic family, Rhinotermitidae. Based on the
      structure of TFP4, the protease inhibitor active loop (Cys(8) to Cys(16)) was
      identified.

PMID- 25978747
TI  - Sneaky Sarcoidosis or a Metastatic Masquerade? - A case of nodular sarcoidosis.
AB  - Sarcoidosis is a multisystem disease of unclear pathogenesis that peaks between
      ages 20 to 39. Sarcoidosis is more common in women and affects blacks three times
      more frequently than whites. Nodular sarcoidosis is a rare variant of sarcoid
      that occurs in 1-4 percent of patients. It presents in female smokers with cough
      and shortness of breath. Nodular sarcoidosis often also presents as multifocal
      bilateral ill-defined nodules mimicking airspace disease or malignancy on
      imaging. Patients generally have a favorable prognosis, with complete resolution
      of the masses with steroid treatment. Herein, we present a case of nodular
      sarcoidosis in a female smoker who presented with cough, weight loss, and fever.
      Imaging revealed multiple pulmonary nodules, a dominant lung mass, and
      lymphadenopathy suggestive of malignancy. Ultimately, the patient underwent
      bronchoscopy and was diagnosed with nodular sarcoidosis; there was no evidence of
      malignancy or infectious process. Resolution of her symptoms ensued with steroid
      treatment. 

PMID- 25978748
TI  - Don't be Half-Educated About Haff Disease in Louisiana.
AB  - Cases of Haff disease, a syndrome of severe myalgia and rhabdomyolysis, have been
      reported after eating cooked fish in Europe and the US. A retrospective review of
      US cases was conducted to identify seafood vectors, describe presenting
      manifestations, and compare the Haff disease toxidrome with other seafood-borne
      toxidromes. Internet search engines were queried to identify all US reports of
      Haff disease. The case definition of Haff disease required cooked seafood
      ingestion history within 24 hours and markedly elevated serum creatine kinase
      (CK) with CK-muscle/brain (MB) fraction < 5 percent. Twenty-six cases of Haff
      disease were reported in the US over 30 years, 1984-2014, with spring-summer
      occurrences. The mean age of cases was 54.8 years without gender difference. Most
      cases (58 percent) followed consumption of cooked buffalo fish, Ictiobus
      cyprinellus, (n = 15); other cases followed consumption of boiled crayfish in
      Louisiana (n = 9) and baked salmon in North Carolina (n = 2). California and
      Louisiana accounted for most cases (n = 18, p = 0.012). Following mean incubation
      periods of eight hours; the most common presenting manifestations included
      vomiting, myalgia, muscle rigidity, chest pain mimicking myocardial infarction,
      diaphoresis, dyspnea, and brown urine indicating myoglobinuria. Most patients
      recovered within 2-5 days. Haff disease may follow the consumption of freshwater
      buffalo fish, freshwater crayfish, and saltwater Atlantic salmon. The
      bioconcentration of a new, unidentified heat-stable, freshwater and/or
      brackish/saltwater algal myotoxin in seafood, similar to palytoxin, is suspected
      of causing Haff disease. Experimental animals fed toxic buffalo fish developed
      rhabdomyolysis with myoglobinuria.

PMID- 25978750
TI  - Mojo Rising - Evaluation and treatment for synthetic marijuana intoxication.

PMID- 25978749
TI  - Hypopharyngeal Airway Surgery for Obstructive Sleep Apnea: Morbidity in the Early
      Postoperative Period.
AB  - STUDY OBJECTIVE: To determine if hypopharyngeal surgery for obstructive sleep
      apnea is associated with significant morbidity in the early post-operative
      period. METHODS: Patients with a diagnosis of obstructive sleep apnea who
      underwent hypopharyngeal surgery at a tertiary care facility between November
      2012 and September 2013 were included in this study. Surgical outcomes were
      assessed from medical records review and a 14 question telephone survey. Results:
      Twenty-two patients underwent hypopharyngeal surgery for obstructive sleep apnea
      (OSA). No patient experienced intra-operative complications, post-operative O2
      desaturation <90%, prolonged admission for inadequate pain control, pulmonary
      edema, or airway compromise requiring re-intubation. Post-operative complications
      included one episode of nasal hemorrhage, one infection requiring
      hospitalization, and one episode of dehydration treated with IV fluids. 25% of
      patients experienced some degree of post-operative dysphonia, and 87.5% of
      patients experienced post-operative dysphagia. The average rating for post
      operative pharyngeal pain was 3.5 of 10 by week 3 and 1.75 of 10 by week 4. Most
      patients described decreased snoring (93.75%), improved feeling of overall health
      (75%), and increased daytime energy (62.5%). All patients undergoing
      hypopharyngeal airway surgery were discharged within 23 hours. CONCLUSION:
      Hypopharyngeal surgery is a safe and well tolerated procedure for the treatment
      of OSA. Our findings suggest that hypopharyngeal surgery may be performed on an
      outpatient basis.

PMID- 25978751
TI  - Prevalence of Integrase Strand Inhibitor Resistance (INSTI)in New Orleans,
      Louisiana, 2012-2013.
AB  - Integrase strand inhibitors (INSTI) are the newest class of antiretroviral (ARV)
      therapies available to patients. There is little surveillance data on INSTI
      resistance, particularly in the South. A retrospective review on all patients who
      underwent PhenoSense Integrase testing between January 1, 2012 and June 30, 2013
      was performed to better identify who should be screened for integrase strand
      transfer inhibitor (INSTI) resistance at the Interim Louisiana State University
      Hospital (ILH). Fifty-three patients underwent PhenoSense testing for
      elvitegravir/raltegravir resistance during this time period. Resistance was
      significantly associated with INSTI experience but not with other characteristics
      including sex, age, race, CD4 cell count, or concurrent reverse transcriptase
      inhibitor or protease inhibitor mutations. The frequency of reduced elvitegravir/
      raltegravir susceptibility among INSTI experienced patients with virologic
      failure at ILH was 14/41 (34%). Future surveillance monitoring will be useful for
      determining if baseline INSTI resistance testing needs to be performed for INSTI
      naive patients in the future at ILH. 

PMID- 25978752
TI  - Bilateral subdural hematomas, an unusual vaso-occlusive event and prolonged
      prothrombin time in a 58-year-old victim of an armed robbery.
AB  - Factor VII deficiency is one of the most common of rare bleeding disorders(1).
      This autosomal recessive disorder has a prevalence of 1:500,000 with geographic
      variations. Clinical manifestations vary from asymptomatic to severe
      mucocutaneous bleeding. According to the International Registry of Factor VII
      Deficiency (IRF7) epistaxis is the most common clinical manifestation.
      Gastrointestinal and central nervous system(CNS) bleeding are rare
      presentations.(2-4) We present here the case of a patient with life-threatening
      CNS bleeding who was found at the age of 58 years to have congenital factor VII
      deficiency. 

PMID- 25978753
TI  - ST Segment Elevation Myocardial Infarction in a 23-Year-Old Woman Following
      Plasmapheresis.
AB  - A 23 year old woman presented with acute ST Elevation Myocardial Infarction
      (STEMI) three hours after donating plasma. Her only risk factors were obesity and
      cigarette smoking. She was found to have ST elevation in the anterior and
      inferior leads. Coronary angiography revealed extensive left anterior descending
      (LAD) thrombosis. Coagulopathy workup was negative. We propose that
      plasmapheresis in a known cigarette smoker led to an acute thrombotic event
      resulting in a STEMI. 

PMID- 25978754
TI  - ECG Case of the Month: ECG in a 20-Year-Old Woman with Dyspnea. Sinus tachycardia
      (104 beats/minute), slight right axis deviation of the QRS (+92 degrees ), an R/S
      ratio greater than 1 in lead V1 with ST depression and T wave inversion in leads
      V1 - V4, and a prominent S wave in lead I, Q wave in lead III, and inverted T
      wave in lead III(S1 Q3 T3). These findings suggest right ventricular hypertrophy
      or strain and are consistent with pulmonary emboli.
AB  - A 20-year-old Hispanic woman presented to the emergency department complaining of
      six months of progressive dyspnea on exertion associated with intermittent
      palpitations. Her only past medical history was a stillbirth at 32 weeks
      gestation about two years ago. Her vital signs in the emergency department were a
      heart rate of 120 beats/minute, a blood pressure of 145/86 mmHg, and an arterial
      oxygen saturation of 98 percent with her breathing air. Significant laboratory
      values included a blood hemoglobin of 14.5 gm/dL, a hematocrit of 49 percent, a
      brain naturetic peptide (BNP) level of 177 pg/mL, a D-dimer level of 330 ng/ml, a
      prothrombin time of 12.85 s with an INR of 1.2, and a partial thromboplastin time
      of 45.7s. Urine pregnancy test was positive, and serum beta-human chorionic
      gonadotropin level was 81 MIU/mL consistent with a fetus of 3-4 weeks gestational
      age. An electrocardiogram was recorded. 

PMID- 25978755
TI  - RADIOLOGY OF THE MONTH: Pulmonary Langerhans Cell Histiocytosis (PLCH).
AB  - PURPOSE: Obtaining a tissue sample diagnostic of pulmonary Langerhans cell
      histiocytosis (PLCH) by transbronchial biopsy is notoriously difficult. The
      condition's appearance on computed tomography is well described and singularly
      characteristic, perhaps adequate for definitive diagnosis. We propose an approach
      to diagnosis of these patients. METHODS: Radiology case report of PLCH in a
      middle-aged female smoker with two week history of nonproductive cough, low grade
      fevers, and fatigue. RESULTS: Computed tomography (CT) provided the diagnosis of
      PLCH. Transbronchial biopsies failed to provide a definitive diagnosis.
      CONCLUSIONS: Utility of transbronchial biopsy in diagnosis of PLCH is limited.
      Patients who present with signs, symptoms and high resolution computed tomography
      typical of PLCH do not require a correlation by tissue diagnosis. If cancer is
      suspected, a wedge biopsy should be performed for tissue diagnosis.

PMID- 25978756
TI  - CLINICAL CASE OF THE MONTH: A 31-Year-Old Man Who Presents with Speech
      Abnormalities.

PMID- 25978757
TI  - PATHOLOGY IMAGE OF THE MONTH: Fatal Acute Necrotizing Pneumonia in a Patient with
      HIV/AIDS.

PMID- 25978758
TI  - Multiple Pontine Perforator Infarction in Basilar Atherosclerosis.

PMID- 25978759
TI  - Reserve Design under Climate Change: From Land Facets Back to Ecosystem
      Representation.
AB  - Ecosystem distributions are expected to shift as a result of global warming,
      raising concerns about the long-term utility of reserve systems based on coarse
      filter ecosystem representation. We tested the extent to which proportional
      ecosystem representation targets would be maintained under a changing climate by
      projecting the distribution of the major ecosystems of Alberta, Canada, into the
      future using bioclimatic envelope models and then calculating the composition of
      reserves in successive periods. We used the Marxan conservation planning software
      to generate the suite of reserve systems for our test, varying the representation
      target and degree of reserve clumping. Our climate envelope projections for the
      2080s indicate that virtually all reserves will, in time, be comprised of
      different ecosystem types than today. Nevertheless, our proportional targets for
      ecosystem representation were maintained across all time periods, with only minor
      exceptions. We hypothesize that this stability in representation arises because
      ecosystems may be serving as proxies for land facets, the stable abiotic
      landscape features that delineate major arenas of biological activity. The
      implication is that accommodating climate change may not require abandoning the
      conventional ecosystem-based approach to reserve design in favour of a strictly
      abiotic approach, since the two approaches may be largely synonymous. 

PMID- 25978760
TI  - Conduction mechanism, impedance spectroscopic investigation and dielectric
      behavior of La0.5Ca0.5-xAgxMnO3 manganites with compositions below the
      concentration limit of silver solubility in perovskites (0 <= x <= 0.2).
AB  - This study presents the electrical properties, complex impedance analysis and
      dielectrical behavior of La0.5Ca0.5-xAgxMnO3 manganites with compositions below
      the concentration limit of silver solubility in perovskites (0 <= x <= 0.2).
      Transport measurements indicate that all the samples have a semiconductor-like
      behavior. The metal-semiconductor transition is not observed across the whole
      temperature range explored [80 K-700 K]. At a specific temperature, a saturation
      region was marked in the sigma (T) curves. We obtained a maximum sigmadc value at
      ambient temperature with the introduction of 20% Ag content. Two hopping models
      were applied to study the conduction mechanism. We found that activation energy
      (Ea) related to ac-conductivity is lower than the Ea implicated in dc
      conductivity. Complex impedance analysis confirms the contribution of grain
      boundary to conductivity and permits the attribution of grain boundary
      capacitance evolution to the temperature dependence of the barrier layer width.
      From the temperature dependence of the average normalized change (ANC), we deduce
      the temperature at which the available density of trapped charge states vanishes.
      Such a temperature is close to the temperature at which the saturation region
      appears in sigma(T) curves. Moreover, complex impedance analysis (CIA) indicates
      the presence of electrical relaxation in materials. It is noteworthy that
      relaxation species such as defects may be responsible for electrical conduction.
      The dielectric behavior of La0.5Ca0.5-xAgxMnO3 manganites has a Debye-like
      relaxation with a sharp decrease in the real part of permittivity at a frequency
      where the imaginary part of permittivity (epsilon'') and tg delta plots versus
      frequency demonstrate a relaxation peak. The Debye-like relaxation is explained
      by Maxwell-Wagner (MW) polarization. Experimental results are found to be in good
      agreement with the Smit and Wijn theory. 

PMID- 25978762
TI  - Abstracts of Posters presented at the 2014 Annual Meeting of the International
      Anesthesia Research Society Montreal, Canada May 17-20, 2014.

PMID- 25978761
TI  - Remote safety monitoring for elderly persons based on omni-vision analysis.
AB  - Remote monitoring service for elderly persons is important as the aged
      populations in most developed countries continue growing. To monitor the safety
      and health of the elderly population, we propose a novel omni-directional vision
      sensor based system, which can detect and track object motion, recognize human
      posture, and analyze human behavior automatically. In this work, we have made the
      following contributions: (1) we develop a remote safety monitoring system which
      can provide real-time and automatic health care for the elderly persons and (2)
      we design a novel motion history or energy images based algorithm for motion
      object tracking. Our system can accurately and efficiently collect, analyze, and
      transfer elderly activity information and provide health care in real-time.
      Experimental results show that our technique can improve the data analysis
      efficiency by 58.5% for object tracking. Moreover, for the human posture
      recognition application, the success rate can reach 98.6% on average. 

PMID- 25978763
TI  - Carbamidomethylation Side Reactions May Lead to Glycan Misassignments in
      Glycopeptide Analysis.
AB  - Iodoacetamide is perhaps the most widely used reagent for the alkylation of free
      sulfhydryls in proteomic experiments. Here, we report that both incomplete
      derivatization of Cys side chains and overalkylation of the peptides may lead to
      the misassignment of glycoforms when LC-MS/MS with electron-transfer dissociation
      (ETD) alone is used for the structural characterization of glycopeptides.
      Accurate mass measurements do not help, because the elemental compositions of the
      misidentified and correct modifications are identical. Incorporation of "higher
      energy C-trap dissociation" (HCD), i.e., beam-type collision-induced dissociation
      data into the database searches with ETD data may prove decisive in most cases.
      However, the carbamidomethylation of Met residues leads to sulfonium ether
      formation, and the resulting fixed positive charge triggers a characteristic
      fragmentation, that eliminates the normal Y1 fragment from the HCD spectra of N
      linked glycopeptides, producing an abundant Y1-48 Da ion instead (the nominal
      mass difference is given relative to the unmodified amino acid sequence), that
      easily can be mistaken for the side chain loss from Met sulfoxide. In such cases,
      good quality ETD data may indicate the discrepancy, and will also display
      abundant fragments due to CH3-S-CH2CONH2 elimination from the charge-reduced
      precursor ions. Our observations also draw attention to the underreported
      interference of different unanticipated covalent modifications. 

PMID- 25978764
TI  - The accuracy of conventional 2D video for quantifying upper limb kinematics in
      repetitive motion occupational tasks.
AB  - Marker-less 2D video tracking was studied as a practical means to measure upper
      limb kinematics for ergonomics evaluations. Hand activity level (HAL) can be
      estimated from speed and duty cycle. Accuracy was measured using a cross
      correlation template-matching algorithm for tracking a region of interest on the
      upper extremities. Ten participants performed a paced load transfer task while
      varying HAL (2, 4, and 5) and load (2.2 N, 8.9 N and 17.8 N). Speed and
      acceleration measured from 2D video were compared against ground truth
      measurements using 3D infrared motion capture. The median absolute difference
      between 2D video and 3D motion capture was 86.5 mm/s for speed, and 591 mm/s(2)
      for acceleration, and less than 93 mm/s for speed and 656 mm/s(2) for
      acceleration when camera pan and tilt were within +/- 30 degrees. Single-camera
      2D video had sufficient accuracy (< 100 mm/s) for evaluating HAL. Practitioner
      Summary: This study demonstrated that 2D video tracking had sufficient accuracy
      to measure HAL for ascertaining the American Conference of Government Industrial
      Hygienists Threshold Limit Value((r)) for repetitive motion when the camera is
      located within +/- 30 degrees off the plane of motion when compared against 3D
      motion capture for a simulated repetitive motion task.

PMID- 25978765
TI  - Primary Bone Tumors: Epidemiologic Comparison of 9200 Patients Treated at Beijing
      Ji Shui Tan Hospital, Beijing, China, With 10 165 Patients at Mayo Clinic,
      Rochester, Minnesota.
AB  - CONTEXT: Although primary bone tumors are extremely rare, the literature suggests
      that there are variations in the epidemiologic characteristics in different
      populations. The most frequently cited epidemiologic characteristics of primary
      bone tumors are derived from a large US series (Mayo Clinic), with no comparable
      study thus far performed in China. OBJECTIVE: To identify any potential
      epidemiologic differences between Chinese patients and a US series of patients.
      DESIGN: We performed a comparison study between 9200 patients treated at Beijing
      Ji Shui Tan Hospital (JST) and 10 165 patients treated at Mayo Clinic (MC),
      Rochester Minnesota. Detailed epidemiologic features were analyzed. RESULTS: We
      found that giant cell tumor and osteosarcoma have significantly higher incidences
      in the JST than the MC patients (P < .001). However, JST patients had a
      significantly lower incidence of Ewing sarcoma, chordoma, fibrosarcoma, myeloma,
      and malignant lymphoma (P < .001). For most benign and malignant bone tumors, the
      Chinese cohort had a more distinct male predominance than the US cohort.
      Malignant bone tumors had a monomodal age distribution in the JST patient group,
      with a bimodal age distribution in the MC cohort. Also, there were was a
      predilection for tumors of the femur and tibia among the JST patients (P < .001).
      CONCLUSIONS: Our data confirm that epidemiologic variations of primary bone
      tumors exist in different populations. Factors that may contribute to these
      observed differences are proposed and discussed.

PMID- 25978766
TI  - Epigenetic Mechanisms of Human Papillomavirus-Associated Head and Neck Cancer.
AB  - CONTEXT: Growing evidence suggests that as many as half of all oropharyngeal
      squamous cell carcinomas (OPSCCs) harbor human papillomavirus (HPV) infections.
      Despite being more advanced at diagnosis, HPV-positive OPSCCs are associated with
      a better response to therapy and longer patient survival than HPV-negative
      OPSCCs. Human papillomavirus-positive OPSCC has also been shown to have distinct
      host gene expression profiles compared with HPV-negative OPSCC. Recently, this
      distinction has been shown to include the epigenome. It is well supported that
      cancers are epigenetically deregulated. This review highlights epigenetic
      differences between HPV-positive and HPV-negative OPSCCs. The epigenetic
      mechanisms highlighted include methylation changes to host and viral DNA, and
      host chromatin modification. We also review the current evidence regarding host
      DNA methylation changes associated with smoking, and deregulation of microRNA
      expression in HPV-positive OPSCC. OBJECTIVE: To provide an overview of epigenetic
      mechanisms reported in HPV-positive OPSCC, with analogies to cervical cancer, and
      discussion of the challenges involved in studying epigenetic changes in HPV
      associated OPSCC in combination with changes associated with smoking. DATA
      SOURCES: Sources were a literature review of peer-reviewed articles in PubMed on
      HPV and either OPSCC or head and neck squamous cell carcinoma, and related
      epigenetic mechanisms. CONCLUSIONS: Epigenetic changes are reported to be a
      contributing factor to maintaining a malignant phenotype in HPV-positive OPSCC.
      The epigenetic mechanisms highlighted in this review can be studied for potential
      as biomarkers or as drug targets. Furthermore, continued research on the
      deregulation of epigenetic mechanisms in HPV-positive OPSCC (compared with HPV
      negative OPSCC) may contribute to our understanding of the clinical and biologic
      differences between HPV-positive and HPV-negative OPSCC.

PMID- 25978767
TI  - Synthesis of amphiphilic polysuccinimide star copolymers for responsive delivery
      in plants.
AB  - While polymeric nanocarriers are widely used in medicine for controlled release
      and site-specific delivery, few reports have applied such delivery methods within
      agriculture, despite the urgent need for specific delivery of pesticides and
      nutrients. We report the synthesis of stimuli-responsive and biodegradable
      polymeric nanocarriers designed for delivery to the phloem of plants and describe
      methods employed to evaluate their toxicity in plant cells. 

PMID- 25978768
TI  - Atomic Force Microscopy Reveals the Mechanobiology of Lytic Peptide Action on
      Bacteria.
AB  - Increasing rates of antimicrobial-resistant medically important bacteria require
      the development of new, effective therapeutics, of which antimicrobial peptides
      (AMPs) are among the promising candidates. Many AMPs are membrane-active, but
      their mode of action in killing bacteria or in inhibiting their growth remains
      elusive. This study used atomic force microscopy (AFM) to probe the
      mechanobiology of a model AMP (a derivative of melittin) on living Klebsiella
      pneumoniae bacterial cells. We performed in situ biophysical measurements to
      understand how the melittin peptide modulates various biophysical behaviors of
      individual bacteria, including the turgor pressure, cell wall elasticity, and
      bacterial capsule thickness and organization. Exposure of K. pneumoniae to the
      peptide had a significant effect on the turgor pressure and Young's modulus of
      the cell wall. The turgor pressure increased upon peptide addition followed by a
      later decrease, suggesting that cell lysis occurred and pressure was lost through
      destruction of the cell envelope. The Young's modulus also increased, indicating
      that interaction with the peptide increased the rigidity of the cell wall. The
      bacterial capsule did not prevent cell lysis by the peptide, and surprisingly,
      the capsule appeared unaffected by exposure to the peptide, as capsule thickness
      and inferred organization were within the control limits, determined by
      mechanical measurements. These data show that AFM measurements may provide
      valuable insights into the physical events that precede bacterial lysis by AMPs. 

PMID- 25978769
TI  - Circumcision and HIV prevention: emerging debates in science, policies and
      programmes.

PMID- 25978770
TI  - Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(III)
      Complexes Having Basic and Nitro Groups and Application to pH Sensing and
      Photoinduced Cell Death.
AB  - Cyclometalated iridium(III) complexes, because of their photophysical properties,
      have the potential for use as luminescent probes for cellular imaging. We
      previously reported on a pH-activatable iridium complex that contains three N,N
      diethylamino groups, namely, fac-Ir(deatpy)3 5, which was synthesized via a
      regioselective aromatic substitution reaction at the 5'-position with
      tolylpyridine groups of fac-Ir(tpy)3 2. It was found that 5 shows a considerable
      enhancement in emission intensity in the pH range from neutral to slightly acidic
      (pH 6.5-7.4) in aqueous solution and selectively stains lysosome in HeLa-S3
      cells, due to the protonation of the diethylamino groups. In addition, 5
      functions as a pH-dependent singlet oxygen ((1)O2) generator and induces necrosis
      like cell death. However, observing the green emission of 5 is often hampered by
      autofluorescence emanating from nearby tissues. To overcome this problem, we
      designed and synthesized a series of new pH-activatable Ir(III) complexes that
      contain diethylamino, guanidyl, and iminoimidazolidinyl groups on the mpiq ligand
      of Ir(mpiq)3 7 and the tfpiq ligand of Ir(tfpiq)3 8, which exhibit a red
      emission, namely, Ir(deampiq)3 13, Ir(gmpiq)3 14, Ir(imzmpiq)3 15, and
      Ir(imztfpiq)3 16. The emission intensity of these Ir complexes is enhanced
      substantially by protonation of their basic groups, and they induce the necrosis
      like cell death of HeLa-S3 cells by photoirradiation at 465 nm. A strong orange
      red emission of Ir(mpiq-NO2)3 9 and Ir(tfpiq-NO2)3 10 is also reported. 

PMID- 25978771
TI  - Almost periodic solutions for a memristor-based neural networks with leakage,
      time-varying and distributed delays.
AB  - In this paper, we study the existence and global exponential stability of almost
      periodic solution for memristor-based neural networks with leakage, time-varying
      and distributed delays. Using a new Lyapunov function method, we prove that this
      delayed neural network has a unique almost periodic solution, which is globally
      exponentially stable. Moreover, the obtained conclusion on the almost periodic
      solution is applied to prove the existence and stability of periodic solution (or
      equilibrium point) for this delayed neural network with periodic coefficients (or
      constant coefficients). 

PMID- 25978772
TI  - Broadband onset inhibition can suppress spectral splatter in the auditory
      brainstem.
AB  - In vivo intracellular responses to auditory stimuli revealed that, in a
      particular population of cells of the ventral nucleus of the lateral lemniscus
      (VNLL) of rats, fast inhibition occurred before the first action potential. These
      experimental data were used to constrain a leaky integrate-and-fire (LIF) model
      of the neurons in this circuit. The post-synaptic potentials of the VNLL cell
      population were characterized using a method of triggered averaging. Analysis
      suggested that these inhibited VNLL cells produce action potentials in response
      to a particular magnitude of the rate of change of their membrane potential. The
      LIF model was modified to incorporate the VNLL cells' distinctive action
      potential production mechanism. The model was used to explore the response of the
      population of VNLL cells to simple speech-like sounds. These sounds consisted of
      a simple tone modulated by a saw tooth with exponential decays, similar to
      glottal pulses that are the repeated impulses seen in vocalizations. It was found
      that the harmonic component of the sound was enhanced in the VNLL cell population
      when compared to a population of auditory nerve fibers. This was because the
      broadband onset noise, also termed spectral splatter, was suppressed by the fast
      onset inhibition. This mechanism has the potential to greatly improve the clarity
      of the representation of the harmonic content of certain kinds of natural sounds.

PMID- 25978774
TI  - The Impact of Antiaromatic Subunits in [4n+2] pi-Systems: Bispentalenes with
      [4n+2] pi-Electron Perimeters and Antiaromatic Character.
AB  - Three series of stable, neutral, pi-extended bispentalene derivatives, with two
      pentalenes fused to a central benzene or naphthalene moiety, have been prepared
      through a modified double carbopalladation cascade reaction. While these
      chromophores feature skeletons with [4n+2] pi-electron perimeters, the two 8 pi
      electron pentalene subunits strongly influence bonding and spectral properties.
      (1)H NMR spectra showed large upfield shifts of the protons in the pentalene
      moieties, comparable to antiaromatic monobenzopentalenes. Further investigations
      on magnetic ring currents through NICS-XY-scans suggest a global paratropic
      current and a local diatropic current at the central benzene ring in two of the
      series, while the third series, with a central naphthalene ring, showed more
      localized ring currents, with stronger paratropic ring currents on the pentalene
      moieties. X-ray diffraction analyses revealed planar bispentalene cores with
      large double- and single-bond alternation in the pentalene units, characteristic
      for antiaromaticity, and small alternation in the central aromatic rings. In
      agreement with TD-DFT calculations, both optical and electrochemical data showed
      much smaller HOMO-LUMO energy gaps compared to other neutral, acene-like
      hydrocarbons with the same number of fused rings. Both experimental and
      computational results suggest that the molecular properties of the presented
      bispentalenes are dominated by the antiaromatic pentalene-subunits despite the
      [4n+2] pi-electron perimeter of the skeletons. 

PMID- 25978773
TI  - Loss of Serglycin Promotes Primary Tumor Growth and Vessel Functionality in the
      RIP1-Tag2 Mouse Model for Spontaneous Insulinoma Formation.
AB  - The serglycin proteoglycan is mainly expressed by hematopoietic cells where the
      major function is to retain the content of storage granules and vesicles. In
      recent years, expression of serglycin has also been found in different forms of
      human malignancies and a high serglycin expression level has been correlated with
      a more migratory and invasive phenotype in the case of breast cancer and
      nasopharyngeal carcinoma. Serglycin has also been implicated in the development
      of the tumor vasculature in multiple myeloma and hepatocellular carcinoma where
      reduced expression of serglycin was correlated with a less extensive vasculature.
      To further investigate the contribution of serglycin to tumor development, we
      have used the immunocompetent RIP1-Tag2 mouse model of spontaneous insulinoma
      formation crossed into serglycin deficient mice. For the first time we show that
      serglycin-deficiency affects orthotopic primary tumor growth and tumor vascular
      functionality of late stage carcinomas. RIP1-Tag2 mice that lack serglycin
      develop larger tumors with a higher proliferative activity but unaltered
      apoptosis compared to normal RIP1-Tag2 mice. The absence of serglycin also
      enhances the tumor vessel functionality, which is better perfused than in tumors
      from serglycin wild type mice. The presence of the pro-angiogenic modulators
      vascular endothelial growth factor and hepatocyte growth factor were decreased in
      the serglycin deficient mice which suggests a less pro-angiogenic environment in
      the tumors of these animals. Taken together, we conclude that serglycin affects
      multiple aspects of spontaneous tumor formation, which strengthens the theory
      that serglycin acts as an important mediator in the formation and progression of
      tumors. 

PMID- 25978775
TI  - Dispersion Corrected Structural Properties and Quasiparticle Band Gaps of Several
      Organic Energetic Solids.
AB  - We have performed ab initio calculations for a series of energetic solids to
      explore their structural and electronic properties. To evaluate the ground state
      volume of these molecular solids, different dispersion correction methods were
      accounted in DFT, namely the Tkatchenko-Scheffler method (with and without self
      consistent screening), Grimme's methods (D2, D3(BJ)), and the vdW-DF method. Our
      results reveal that dispersion correction methods are essential in understanding
      these complex structures with van der Waals interactions and hydrogen bonding.
      The calculated ground state volumes and bulk moduli show that the performance of
      each method is not unique, and therefore a careful examination is mandatory for
      interpreting theoretical predictions. This work also emphasizes the importance of
      quasiparticle calculations in predicting the band gap, which is obtained here
      with the GW approximation. We find that the obtained band gaps are ranging from 4
      to 7 eV for the different compounds, indicating their insulating nature. In
      addition, we show the essential role of quasiparticle band structure calculations
      to correlate the gap with the energetic properties. 

PMID- 25978776
TI  - Four new neolignan glucosides from the fruits of Arctium lappa.
AB  - Four new neolignan glucosides named (7S, 8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy
      8-O-4'-neolignan-9'-O-beta-d-apiofuranosyl-(1 -> 6)-O-beta-d-glucopyranoside (1),
      (8R)-4,9,9'-trihydroxy-3,3'-dimethoxy-7-oxo-8-O-4'-neolignan-4-O-beta-d
      glucopyranoside (2), (7R, 8S)-dihydrodehydrodiconiferyl alcohol-7'-oxo-4-O-beta-d
      glucopyranoside (3), and (7'S, 8'R, 8S)-4,4',9'-trihydroxy-3,3'-dimethoxy-7',9
      epoxylignan-7-oxo-4-O-beta-d-glucopyranoside (4) were isolated from the fruits of
      Arctium lappa L. Their structures and absolute configurations were elucidated on
      the basis of comprehensive spectroscopic analyses (UV, IR, HR-ESI-MS, 1D and 2D
      NMR, CD), as well as by comparison with known analogues in the literature. 

PMID- 25978777
TI  - An outcome study of a 2-flap pushback palatoplasty used in the treatment of wide
      cleft palates.
AB  - Cleft palate remains a common congenital deformity. The wide cleft palate in
      particular presents a unique challenge when attempting to restore a competent
      velopharyngeal mechanism. We present an outcome study of a single surgeon's
      experience using a modified surgical technique designed to specifically address
      the wide cleft palate. The surgical technique consisted of a 2-flap pushback
      palatoplasty without nasal mucosa closure combined with an end-to-end intravelar
      veloplasty and was used in cleft palates greater than or equal to 10 mm in width.
      A retrospective, longitudinal outcome study from chart review was then performed
      where age at surgery, sex, Veau classification of the cleft type, and follow-up
      length were recorded for each patient. Postsurgery speech outcomes were assessed
      by standardized speech evaluation performed by a speech language pathologist, and
      the presence and location of unplanned oronasal fistulas were recorded. Our study
      revealed an overall incidence of velopharyngeal insufficiency (VPI) of 10.8% and
      an unplanned symptomatic fistula rate of 16.8%. There was a significant
      correlation between the Veau classification of the cleft type with the incidence
      of both VPI and the occurrence of an unplanned oronasal fistula. Application of
      this surgical technique, specifically to wider cleft palates, resulted in VPI and
      fistula rates comparable to rates reported with other techniques used in clefts
      of all widths. Additional information regarding subsequent growth disturbances of
      the craniofacial skeleton in these patients is currently being collected.

PMID- 25978779
TI  - Complete eruption of a deeply impacted tooth in a recurrent keratocystic
      odontogenic tumor with orthodontic occlusal alignment.

PMID- 25978780
TI  - Nonsyndrome multiple supernumerary teeth.

PMID- 25978781
TI  - Surgical approach in a large ameloblastic fibrodentinoma.

PMID- 25978782
TI  - Interdental papillae reconstruction in glossopelvectomy defects.

PMID- 25978783
TI  - Delayed replantation of avulsed maxillary incisors and alveolar bone.

PMID- 25978784
TI  - Fat-Removal Orbital Decompressing for Severe Bilateral Proptosis due to Weber
      Christian Disease.

PMID- 25978785
TI  - To computer-aided design and manufacturing or not to computer-aided design and
      manufacturing? Free fibula flap with computer-aided technique for mandibular
      reconstruction.
AB  - AIM: The purpose of this study was to analyze the accuracy of computer-assisted
      free fibula flap for reconstruction of large mandibular defects for benign
      tumors. MATERIALS AND METHODS: Between December 2012 and January 2014, a total of
      4 free osteocutaneous computer-assisted fibula flaps have been used in an equal
      number of patients for reconstruction of the mandible at the Division of
      Maxillofacial Surgery, Citta della Scienza e della Salute Hospital, University of
      Turin. Inclusion criteria were large mandibular defects due to benign tumors. The
      computer-assisted fibula flap was chosen when 2 or more osteotomies were
      requested. Intraoperative complication, mean ischemia time, operative time, and
      morphologic outcomes were analyzed in all cases. After surgery, a postoperative
      computed tomography compared the virtual plan with the surgical results. RESULTS:
      All 3 flaps were harvested and transplanted successfully. For the free flaps
      examined in this work, no intraoperative complications were noted. Postoperative
      computed tomography showed high correspondence in terms of bone contour according
      to the virtual plan. The immediate and long-term morphologic results were
      satisfactory. CONCLUSIONS: Microsurgical mandible reconstruction using a computer
      assisted fibula flap technique is the best available method to manage complex
      defects.

PMID- 25978786
TI  - Stability, redox parameters and electrocatalytic activity of a cytochrome domain
      from a new subfamily.
AB  - We report a spectroscopic, electrochemical and spectroelectrochemical
      characterization of the soluble cytochrome c domain (Cyt-D) from the Rhodothermus
      marinus caa3 terminal oxygen reductase and its putative electron donor, a high
      potential [4Fe-4S] protein (HiPIP). Cyt-D exhibits superior stability,
      particularly at the level of the heme pocket, compared to archetypical
      cytochromes in terms of thermal and chemical denaturation, alkaline transition
      and oxidative bleaching of the heme, which is further increased upon adsorption
      on biomimetic electrodes. Therefore, this protein is proposed as a suitable
      building block for electrochemical biosensing. As a proof of concept, we show
      that the immobilized Cyt-D exhibits good electrocatalytic activity towards H2O2
      reduction. Relevant thermodynamic and kinetic electron transfer parameters for
      Cyt-D and HiPIP are also reported, including reorganization energies of 0.33 eV
      and 0.42 eV, respectively.

PMID- 25978787
TI  - Compressible Viscoelastic Liquid Effects Generated by the Breathing Modes of
      Isolated Metal Nanowires.
AB  - Transient absorption microscopy is used to examine the breathing modes of single
      gold nanowires in highly viscous liquids. By performing measurements on the same
      wire in air and liquid, the damping contribution from the liquid can be separated
      from the intrinsic damping of the nanowire. The results show that viscous liquids
      strongly reduce the vibrational lifetimes but not to the extent predicted by
      standard models for nanomaterial-liquid interactions. To explain these results a
      general theory for compressible viscoelastic fluid-structure interactions is
      developed. The theory results are in good agreement with experiment, which
      confirms that compressible non-Newtonian flow phenomena are important for
      vibrating nanostructures. This is the first theoretical study and experimental
      measurement of the compressible viscoelastic properties of simple liquids. 

PMID- 25978788
TI  - Cryptic noninnocence: FeNO corroles in a new light.
AB  - Multiple lines of evidence, including electronic absorption spectroscopy,
      infrared spectroscopy, and broken-symmetry DFT calculations, indicate that the
      well-known FeNO corroles, long assumed to be {FeNO}(6) complexes, are in fact
      better described as {FeNO}(7)-(corrole(2-)). 

PMID- 25978790
TI  - Editorial: Sick Children are Greater than the Sum of Their Parts: Does Family
      Centered Care Promote Holistic Practice?

PMID- 25978789
TI  - Cognitive improvements in a mouse model with substituted 1,2,3-triazole agonists
      for nicotinic acetylcholine receptors.
AB  - The alpha7 nicotinic acetylcholine receptor (nAChR) is a recognized drug target
      for dementias of aging and certain developmental disorders. Two selective and
      potent alpha7-nAChR agonists, winnowed from a list of 43 compounds characterized
      in a companion article (DOI: 10.1021/acschemneuro.5b00058), 5-((quinuclid-3-yl)
      1H-1,2,3-triazol-4-yl)-1H-indole (IND8) and 3-(4-hydroxyphenyl-1,2,3-triazol-1
      yl) quinuclidine (QND8), were evaluated for cognitive improvement in both short-
      and long-term memory. Tacrine, a centrally active acetylcholinesterase inhibitor,
      and PNU-282987, a congeneric alpha7 nAChR agonist, were employed as reference
      standards. Three behavioral tests, modified Y-maze, object recognition test
      (ORT), and water maze, were performed in scopolamine-induced amnesic mice.
      Intraperitoneal injection of these two compounds significantly improved the
      cognitive impairment in a modified Y-maze test (5 MUmol/kg for IND8 and 10
      MUmol/kg for QND8), ORT (10 MUmol/kg), and water maze test (25 MUmol/kg). For
      delay induced memory deficit or natural memory loss in mice, IND8 and QND8 at 10
      MUmol/kg were able to enhance memory comparable to PNU-282987 when evaluated
      using ORT time delay model. Cognitive enhancement of IND8 and QND8 was mediated
      through alpha7-nAChRs as evidenced by its complete abolition after pretreatment
      with a selective alpha7-nAChR antagonist, methyllycaconitine. These data
      demonstrate that IND8 and QND8 and their congeners are potential candidates for
      treatment of cognitive disorders, and the substituted triazole series formed by
      cycloaddition of alkynes and azides warrant further preclinical optimization. 

PMID- 25978791
TI  - Chemical composition, N-nitrosamine inhibition and antioxidant and antimicrobial
      properties of essential oil from Coreopsis tinctoria flowering tops.
AB  - Coreopsis tinctoria flowering (CTF) tops from the Kunlun Mountains in Xinjing
      (north-western China) have been used for tea production for about a century. This
      study was to assess antioxidant, nitrite-scavenging and N-nitrosamine inhibitory
      and antimicrobial activities of the essential oil extracted from CTF tops. The
      essential oil was extracted through hydrodistillation and its chemical
      compositions were analysed by GC-MS. Seventy compounds of the oil were
      identified, representing 81.87% of total oil. The antioxidant capacities of the
      oil with IC50 values for scavenging DPPH and ABTS were 287.66 +/- 12.60 and 1.251
      +/- 0.127 MUg mL(- 1), respectively. The nitrite-scavenging and N-nitrosamine
      inhibitory activities (IC50) were 0.3912 +/- 0.0127 and 0.6564 +/- 0.036 MUg mL(-
      1), respectively. The oil has a certain antimicrobial capacity, but its capacity
      was weaker than that of penicillinG (24 MUg mL(- 1)). The oil showed antioxidant
      and antimicrobial capacities and had a stronger nitrite-scavenging and N
      nitrosamine inhibitory properties.

PMID- 25978792
TI  - Adsorption behavior comparison of trivalent and hexavalent chromium on biochar
      derived from municipal sludge.
AB  - In this work, static equilibrium experiments were conducted to distinguish the
      adsorption performance between the two valence states of chromium on biochar
      derived from municipal sludge. The removal capacity of Cr(VI) is lower than 7mg/g
      at the initial chromium concentration range of 50-200mg/L, whereas that of
      Cr(III) higher than 20mg/g. It indicates that Cr(III) is much easier to be
      stabilized than Cr(VI). No significant changes in the biochar surface functional
      groups are observed before and after the adsorption equilibrium, demonstrating
      the poor contribution of organic matter in chromium adsorption. The main
      mechanism of heavy metal adsorption by biochar involves (1) surface precipitation
      through pH increase caused by biochar buffer ability, and (2) exchange between
      cations in solution (Cd(2+)) and in biochar matrix (e.g. Ca(2+) and Mg(2+)). The
      reduction of Cr(VI) to Cr(III) is necessary to improve removal efficiency of
      chromium. 

PMID- 25978793
TI  - Long-term Exposure to Particulate Matter Constituents and the Incidence of
      Coronary Events in 11 European Cohorts.
AB  - BACKGROUND: Long-term exposure to particulate matter (PM) has been associated
      with increased cardiovascular morbidity and mortality but little is known about
      the role of the chemical composition of PM. This study examined the association
      of residential long-term exposure to PM components with incident coronary events.
      METHODS: Eleven cohorts from Finland, Sweden, Denmark, Germany, and Italy
      participated in this analysis. 5,157 incident coronary events were identified
      within 100,166 persons followed on average for 11.5 years. Long-term residential
      concentrations of PM < 10 MUm (PM10), PM < 2.5 MUm (PM2.5), and a priori selected
      constituents (copper, iron, nickel, potassium, silicon, sulfur, vanadium, and
      zinc) were estimated with land-use regression models. We used Cox proportional
      hazard models adjusted for a common set of confounders to estimate cohort
      specific component effects with and without including PM mass, and random effects
      meta-analyses to pool cohort-specific results. RESULTS: A 100 ng/m3 increase in
      PM10 K and a 50 ng/m3 increase in PM2.5 K were associated with a 6% (hazard ratio
      and 95% confidence interval: 1.06 [1.01, 1.12]) and 18% (1.18 [1.06, 1.32])
      increase in coronary events. Estimates for PM10 Si and PM2.5 Fe were also
      elevated. All other PM constituents indicated a positive association with
      coronary events. When additionally adjusting for PM mass, the estimates decreased
      except for K. CONCLUSIONS: This multicenter study of 11 European cohorts pointed
      to an association between long-term exposure to PM constituents and coronary
      events, especially for indicators of road dust.

PMID- 25978794
TI  - Obesity and risk of infection: results from the Danish Blood Donor Study.
AB  - BACKGROUND: It is well known that obesity complicates the course of several
      diseases. However, it is unknown whether obesity affects the risk of infection
      among healthy individuals. METHODS: We included 37,808 healthy participants from
      the Danish Blood Donor Study, who completed a questionnaire on health-related
      items. Obesity was defined as a body mass index >= 30 kg/m(2). Infections among
      participants were identified by relevant ICD-10 codes in the Danish National
      Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish
      Prescription Register. Multivariable Cox proportional hazards analysis with age
      as the underlying timescale was used as the statistical model. RESULTS: During
      113,717 person-years of observation, 1,233 participants were treated for
      infection at a hospital. Similarly, during 58,411 person-years of observation,
      15,856 participants filled at least one prescription of antimicrobials. Obesity
      was associated with risk of hospital-based treatment for infection (women: hazard
      ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI
      = 1.2, 1.9). For specific infections, obesity was associated with increased risk
      of abscesses (both sexes), infections of the skin and subcutaneous tissue (men),
      and respiratory tract infections and cystitis (women). Similarly, obesity was
      associated with filled prescriptions of antimicrobials overall (women: HR = 1.22,
      95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with
      phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad
      spectrum penicillins. CONCLUSIONS: In a large cohort of healthy individuals,
      obesity was associated with risk of infection. This result warrants further
      studies of metabolism and the immune response.

PMID- 25978795
TI  - Cannabis Smoking and Diabetes Mellitus: Results from Meta-analysis with Eight
      Independent Replication Samples.
AB  - BACKGROUND: In preclinical animal studies, evidence links cannabis with
      hyperphagia, obesity, and insulin resistance. Epidemiologic data, however,
      suggest an inverse cannabis smoking-diabetes mellitus association. Here, we offer
      epidemiologic estimates from eight independent replications from (1) the National
      Health and Nutrition Examination Surveys, and (2) the National Surveys on Drug
      Use and Health (2005-2012). METHODS: For each national survey participant,
      computer-assisted self-interviews assess cannabis smoking and physician-diagnosed
      diabetes mellitus; the National Health and Nutrition Examination Surveys provide
      additional biomarker values and a composite diabetes diagnosis. Regression
      analyses produce estimates of cannabis smoking-diabetes associations. Meta
      analyses summarize the replication estimates. RESULTS: Recently active cannabis
      smoking and diabetes mellitus are inversely associated. The meta-analytic summary
      odds ratio is 0.7 (95% confidence interval = 0.6, 0.8). CONCLUSIONS: Current
      evidence is too weak for causal inference, but there now is a more stable
      evidence base for new lines of clinical translational research on a possibly
      protective (or spurious) cannabis smoking-diabetes mellitus association suggested
      in prior research.

PMID- 25978796
TI  - Toward a clearer portrayal of confounding bias in instrumental variable
      applications.
AB  - Recommendations for reporting instrumental variable analyses often include
      presenting the balance of covariates across levels of the proposed instrument and
      levels of the treatment. However, such presentation can be misleading as
      relatively small imbalances among covariates across levels of the instrument can
      result in greater bias because of bias amplification. We introduce bias plots and
      bias component plots as alternative tools for understanding biases in
      instrumental variable analyses. Using previously published data on proposed
      preference-based, geography-based, and distance-based instruments, we demonstrate
      why presenting covariate balance alone can be problematic, and how bias component
      plots can provide more accurate context for bias from omitting a covariate from
      an instrumental variable versus non-instrumental variable analysis. These plots
      can also provide relevant comparisons of different proposed instruments
      considered in the same data. Adaptable code is provided for creating the plots. 

PMID- 25978797
TI  - An even clearer portrait of bias in observational studies?

PMID- 25978798
TI  - Characterizing the acid/base behavior of oil-soluble surfactants at the interface
      of nonpolar solvents with a polar phase.
AB  - We propose a simple method of characterizing the (Lewis) acid/base behavior of
      oil-soluble nonionic surfactants at the interface of nonpolar solvents with a
      polar phase. Using interfacial tensiometry, we probe the effective acidic and
      basic response of nonpolar surfactant solutions to contact with a variety of
      polar reference liquids. The measured interfacial tensions are used as
      experimental coefficients in a set of equations borrowed from the thermodynamic
      "surface energy component model" of van Oss, Chaudhury, and Good (vOCG), but used
      here in a more heuristic fashion and with a revised interpretation of the
      parameters extracted to describe the dispersive, acidic, and basic character of
      the sample. We test the proposed characterization method using alkane solutions
      of purified polyisobutylene succinimide (PIBS) surfactants with systematic
      structural variations, and observe that the inferred parameter values are
      consistent with, and sensitive to, subtle differences in the surfactant
      chemistry. This suggests the possibility to compare different surfactant
      solutions semiquantitatively with regard to their acidic and basic character. In
      a further illustration of the proposed analysis, we characterize a solution of
      commercial PIBS surfactant in hexane, and find that the parameters obtained by
      the proposed method correctly predict the solution interfacial tension with a
      polar liquid not included among the chosen reference liquids. 

PMID- 25978800
TI  - Longitudinal cognitive development of children born to mothers with opioid and
      polysubstance use.
AB  - BACKGROUND: Previous studies indicate an increased risk for neuropsychological
      difficulties in young children prenatally exposed to opioids and polysubstances,
      but longitudinal information is scarce. The present longitudinal study
      investigated whether these waned, persisted, or increased over time. METHODS: The
      cognitive functioning of 72 children with prenatal opioid and polysubstance
      exposure and 58 children without any established prenatal risk was assessed at 1,
      2, 3, 41/2, and 81/2 y. RESULTS: The exposed boys had significantly and stably
      lower levels of cognitive functioning than the control group, whereas there were
      increasing differences over time for the girls. The exposed group had
      significantly lower IQ scores than the control group on Wechsler Intelligence
      Scale for Children--Revised at 81/2 y after controlling for earlier cognitive
      abilities, and for children who were permanently placed in adoptive/foster homes
      before 1 y of age and whose mothers used heroin as their main drug during
      pregnancy (B = 17.04, 95% CI 8.69-25.38, P < 0.001). CONCLUSION: While effects of
      prenatal substance exposure cannot be isolated, group effects on cognition rather
      increased than waned over time, even in adoptive/foster children with minimal
      postnatal risk.

PMID- 25978801
TI  - Do children with congenital hypothyroidism exhibit abnormal cortical morphology?
AB  - BACKGROUND: Given thyroid hormone (TH)'s essential role in multiple aspects of
      early brain development, children with congenital hypothyroidism (CH) detected
      and treated early may still display subtle cognitive and behavioral impairments
      as well as brain abnormalities. However, effects on their cortical development
      are not yet known. We used an automated neuroimaging technique to determine if
      these children differ in cortical thickness (CT) from typically developing
      controls (TDC) and if the regions showing CT differences reflect severity of
      initial hypothyroidism and predict later neuropsychological functioning. METHODS:
      FreeSurfer Image Analysis Suite was used on archived MRI scans from 41 CH and 42
      TDC children aged 9-16 y. Vertex-based procedures were used to compare groups and
      perform correlations between CT and indices of disease severity and
      neuropsychological outcome. RESULTS: The CH group showed multiple regions of
      cortical thinning or cortical thickening within right and left hemispheres
      relative to TDC. CT values were significantly correlated with early T4 and
      thyroid-stimulating hormone (TSH) levels and current neuropsychological test
      indices. CONCLUSION: The developing cortex is sensitive to early TH loss in CH.
      Different patterns of cortical thinning or cortical thickening among brain
      regions may reflect timing of TH deficiency relative to timing of cortical
      development.

PMID- 25978803
TI  - A systematic review of studies on Escherichia coli and Enterobacteriaceae on beef
      carcasses at the slaughterhouse.
AB  - European legislation has defined as process hygiene criteria for the main
      livestock species (cattle, sheep, goats, horses and pigs) the monitoring of
      aerobic colony count and Enterobacteriaceae. Detected values above the defined
      criteria require an improvement in slaughter hygiene and the review of process
      control. The main source of microbiological contamination of beef carcasses along
      the slaughterline is of fecal origin, therefore Escherichia coli and
      Enterobacteriaceae seem to be the most suitable indicators to assess the hygienic
      status of the slaughter process. Although microbiological criteria addressing
      indicator bacteria have been in place in industrialized countries for several
      years, scattered information still exists on factors affecting their counts on
      beef carcasses along the slaughterline. Therefore, a systematic literature
      review, covering the period 2000-2012, was conducted to gather information
      concerning: 1) counts of E. coli and Enterobacteriaceae on beef carcasses linked
      to different stages of the slaughterline; 2) factors influencing presence/counts
      of E. coli and Enterobacteriaceae on beef carcasses; and 3) the relationship
      between indicator bacteria (E. coli and Enterobacteriaceae) counts and visual
      fecal contamination of beef carcasses. According to the 41 retrieved papers the
      following conclusions were drawn. A decrease of the indicator bacteria counts was
      recorded after sequential decontamination treatments, such as pasteurization and
      hot water washing. Slaughterhouse characteristics influenced bacterial load of
      beef carcasses, although it was difficult to assess which factors (i.e.,
      slaughterhouse throughput, design of the plant, surveillance system in place) had
      the greatest effect. Finally, carcasses from fecal contaminated animals had
      higher bacterial loads than those from clean animals. Therefore, the development
      of a visual classification system of the level of dirtiness of carcasses and the
      application of effective treatments on the carcasses classified as dirty along
      the slaughterline can lead to a contamination level for these carcasses
      comparable to or lower than that of originally clean ones at the end of the
      slaughterline. 

PMID- 25978799
TI  - The NIEHS Superfund Research Program: 25 Years of Translational Research for
      Public Health.
AB  - BACKGROUND: The Superfund Research Program (SRP) is an academically based,
      multidisciplinary, translational research program that for 25 years has sought
      scientific solutions to health and environmental problems associated with
      hazardous waste sites. SRP is coordinated by the National Institute of
      Environmental Health Sciences (NIEHS). It supports multi-project grants,
      undergraduate and postdoctoral training programs, individual research grants, and
      Small Business Innovation Research (SBIR) and Technology Transfer Research (STTR)
      grants. RESULTS: SRP has had many successes: discovery of arsenic's toxicity to
      the developing human central nervous system; documentation of benzene toxicity to
      hematologic progenitor cells in human bone marrow; development of novel analytic
      techniques such as the luciferase expression assay and laser fragmentation
      fluorescence spectroscopy; demonstration that PCBs can cause developmental
      neurotoxicity at low levels and alter the genomic characteristics of sentinel
      animals; elucidation of the neurodevelopmental toxicity of organophosphate
      insecticides; documentation of links between antimicrobial agents and alterations
      in hormone response; discovery of biological mechanisms through which
      environmental chemicals may contribute to obesity, atherosclerosis, diabetes, and
      cancer; tracking the health and environmental effects of the attacks on the World
      Trade Center and Hurricane Katrina; and development of novel biological and
      engineering techniques to facilitate more efficient and lower-cost remediation of
      hazardous waste sites. CONCLUSION: SRP must continue to address the legacy of
      hazardous waste in the United States, respond to new issues caused by rapid
      advances in technology, and train the next generation of leaders in environmental
      health science while recognizing that most of the world's worst toxic hot spots
      are now located in low- and middle-income countries.

PMID- 25978802
TI  - Neonatal DTI early after birth predicts motor outcome in preterm infants with
      periventricular hemorrhagic infarction.
AB  - BACKGROUND: To determine the association between early neonatal diffusion tensor
      imaging (DTI) and the development of unilateral spastic cerebral palsy (USCP) in
      preterm infants with periventricular hemorrhagic infarction (PVHI). METHODS:
      Preterm infants with PVHI were assessed with early (<=4 wk after birth) and term
      equivalent age MRI-DTI. Involvement of corticospinal tracts was assessed by
      visual assessment of the posterior limb of the internal capsule (PLIC) on DTI
      (classified asymmetrical, equivocal, or symmetrical) and by an atlas-based
      approach calculating fractional anisotropy asymmetry index in the PLIC. Motor
      outcome was assessed at >=15 mo corrected age. RESULTS: Seven out of 23 infants
      with PVHI developed USCP. Their PLIC was visually scored as asymmetrical in 6 and
      equivocal in 1 on the early DTI. Thirteen out of 16 infants with a symmetrical
      motor development had a symmetrical PLIC on early DTI, the remaining 3 were
      equivocal. All infants with USCP had a fractional anisotropy asymmetry index of
      >0.05 (optimal cut-off value) on early DTI. In infants with a symmetrical motor
      development (n = 16), 14 had an asymmetry index <=0.05 while 2 had an index
      >0.05. CONCLUSION: DTI in preterm infants with PVHI within a few weeks after
      birth is associated with later motor development.

PMID- 25978804
TI  - Molecular docking study of macrocycles as Fk506-binding protein inhibitors.
AB  - To prepare for future resistance, new methods are being explored for novel
      treatment of malaria. The current work uses high performance docking methods to
      model different substrates binding into the active sites of varying Homo sapien
      and Plasmodium peptidyl-prolyl cis/trans isomerase enzymes and compares their
      subsequent docking scores. This approach has shown that the substrates ILS-920
      and WYE-592 will bind less-favourably with hFKBP12 and PfFKBP35 compared to a
      competing substrate rapamycin; however, the binding appears to be more favourable
      in PvFKBP35. This could suggest a possible target for inhibition of the
      Plasmodium vivax parasite. 

PMID- 25978805
TI  - Structural effects of tachyplesin I and its linear derivative on their
      aggregation and mobility in lipid bilayers.
AB  - We performed coarse-grained molecular dynamics simulations of tachyplesin I (TP
      I), which is a beta-hairpin antimicrobial peptide with two disulfide bonds, and
      its linearly extended derivative without disulfide bonds (TPA4) in lipid bilayers
      for 5MUs. beta-hairpin TP-I peptides tend to individually bind to the bilayer
      surface, while linear TPA4 peptides aggregate and form the beta-strand complex on
      the bilayer surface, indicating the effect of the peptide structure on
      aggregation. Also, TPA4 more slowly diffuse along the bilayer surface than do TP
      I, indicating that aggregated beta-strands of TPA4 cannot diffuse as fast as
      individual beta-hairpins of TP-I. TPA4 have the stronger charge interaction with
      lipid head groups than do TP-I, leading to the deeper insertion into the bilayer.
      These simulation results indicate that TP-I peptides tend to individually exist
      on the bilayer surface and thus easily diffuse along the bilayer surface, while
      TPA4 peptides aggregate as beta-strands, which limits the lateral mobility of
      TPA4, leading to a strong immobilization of TPA4. These findings agree well with
      the experimentally observed dependence of peptide mobility on the peptide
      structure in membranes, as well as support experimental suggestions regarding the
      formation of beta-strand complexes of linear TPA4 and the relationship between
      the peptide aggregation and mobility. 

PMID- 25978806
TI  - Thrombocytopaenia and neutropaenia associated with daptomycin USE.
AB  - Daptomycin is a lipopeptide antibiotic active against gram-positive bacteria
      indicated for the treatment of complicated skin and skin structure infections and
      Staphylococcus aureus bloodstream infections, including endocarditis.
      Thrombocytopaenia, but not neutropaenia, is described as a possible or probable
      adverse effect in the product information. Up to now, two case reports of
      daptomycin-induced thrombocytopaenia have been published and a single case of
      neutropaenia associated with prolonged daptomycin use. We report a case of
      simultaneous thrombocytopaenia and neutropaenia associated with prolonged
      daptomycin use for a culture-negative endocarditis. 

PMID- 25978808
TI  - What's New in Shock? JUNE 2015.

PMID- 25978807
TI  - A multiplexed device based on tunable nanoshearing for specific detection of
      multiple protein biomarkers in serum.
AB  - Microfluidic flow based multiplexed devices have gained significant promise in
      detecting biomarkers in complex biological samples. However, to fully exploit
      their use in bioanalysis, issues such as (i) low sensitivity and (ii) high levels
      of nonspecific adsorption of non-target species have to be overcome. Herein, we
      describe a new multiplexed device for the sensitive detection of multiple protein
      biomarkers in serum by using an alternating current (ac) electrohydrodynamics (ac
      EHD) induced surface shear forces based phenomenon referred to as nanoshearing.
      The tunable nature (via manipulation of ac field) of these nanoshearing forces
      can alter the capture performance of the device (e.g., improved fluid transport
      enhances number of sensor-target collisions). This can also selectively displace
      weakly (nonspecifically) bound molecules from the electrode surface (i.e., fluid
      shear forces can be tuned to shear away nonspecific species present in biological
      samples). Using this approach, we achieved sensitive (100 fg mL(-1)) naked eye
      detection of multiple protein targets spiked in human serum and a 1000-fold
      enhancement in comparison to hydrodynamic flow based devices for biomarker
      detection. We believe that this approach could potentially represent a clinical
      diagnostic tool that can be integrated into resource-limited settings for
      sensitive detection of target biomarkers using naked eye.

PMID- 25978809
TI  - Glucagon levels, disease severity, and outcome in severe sepsis.
AB  - PURPOSE: Few studies on plasma glucagon levels in patients with sepsis have been
      performed. We aimed to assess clinical value of glucagon levels in comparison
      with clinical parameters and severity scores in patients with severe sepsis or
      septic shock. METHODS: A total of 112 patients who were admitted to intensive
      care unit with severe sepsis or septic shock were included. Plasma levels of
      glucagon on days 0, 1, 3, and 7 were serially measured in 112 patients with
      severe sepsis or septic shock. RESULTS: Compared with survivors, patients who
      died within 28 days had significantly higher glucagon levels on every day of
      examination. Glucagon levels were positively correlated with and Acute Physiology
      and Chronic Health Evaluation II score (day 0, r = 0.288, P < 0.01) and
      Sequential Organ Failure Assessment (day 0, r = 0.482, P< 0.01; day 1, r = 0.588,
      P < 0.01; day 3, r = 0.480, P < 0.01; day 7, r = 0.454, P < 0.01). Receiver
      operating characteristic analysis showed that the area under the curve of
      glucagon levels to predict 28-day survival was 0.65 (95% confidence interval
      [CI], 0.55-0.75; P = 0.005), similar to the Acute Physiology and Chronic Health
      Evaluation II and Sequential Organ Failure Assessment scores. Multivariate
      analysis revealed that glucagon levels of greater than 70 pg/mL (hazard ratio,
      1.85; 95% CI, 1.03-3.29) and chronic liver disease (hazard ratio, 1.97; 95% CI,
      1.02-3.79) were associated with mortality. CONCLUSIONS: Glucagon levels might
      reflect disease severity and clinical outcomes in patients with severe sepsis or
      septic shock.

PMID- 25978810
TI  - Expression of concern.

PMID- 25978815
TI  - Correction: correction: plastidic phosphoglucose isomerase is an important
      determinant of starch accumulation in mesophyll cells, growth, photosynthetic
      capacity, and biosynthesis of plastidic cytokinins in Arabidopsis.

PMID- 25978816
TI  - Treatment with serotonin reuptake inhibitors during pregnancy is associated with
      elevated corticotropin-releasing hormone levels.
AB  - Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an
      increased risk of preterm birth, but causality remains unclear. While placental
      CRH production is correlated with gestational length and preterm birth, it has
      been difficult to establish if psychological stress or mental health problems are
      associated with increased CRH levels. This study compared second trimester CRH
      serum concentrations in pregnant women on SSRI treatment (n=207) with untreated
      depressed women (n=56) and controls (n=609). A secondary aim was to investigate
      the combined effect of SSRI treatment and CRH levels on gestational length and
      risk for preterm birth. Women on SSRI treatment had significantly higher second
      trimester CRH levels than controls, and untreated depressed women. CRH levels and
      SSRI treatment were independently associated with shorter gestational length. The
      combined effect of SSRI treatment and high CRH levels yielded the highest risk
      estimate for preterm birth. SSRI treatment during pregnancy is associated with
      increased CRH levels. However, the elevated risk for preterm birth in SSRI users
      appear not to be mediated by increased placental CRH production, instead CRH
      appear as an independent risk factor for shorter gestational length and preterm
      birth. 

PMID- 25978814
TI  - Avoiding false positive antigen detection by flow cytometry on blood cell derived
      microparticles: the importance of an appropriate negative control.
AB  - BACKGROUND: Microparticles (MPs), also called microvesicles (MVs) are plasma
      membrane-derived fragments with sizes ranging from 0.1 to 1MUm. Characterization
      of these MPs is often performed by flow cytometry but there is no consensus on
      the appropriate negative control to use that can lead to false positive results.
      MATERIALS AND METHODS: We analyzed MPs from platelets, B-cells, T-cells, NK
      cells, monocytes, and chronic lymphocytic leukemia (CLL) B-cells. Cells were
      purified by positive magnetic-separation and cultured for 48h. Cells and MPs were
      characterized using the following monoclonal antibodies (CD19,20 for B-cells,
      CD3,8,5,27 for T-cells, CD16,56 for NK-cells, CD14,11c for monocytes, CD41,61 for
      platelets). Isolated MPs were stained with annexin-V-FITC and gated between 300nm
      and 900nm. The latex bead technique was then performed for easy detection of MPs.
      Samples were analyzed by Transmission (TEM) and Scanning Electron microscopy
      (SEM). RESULTS: Annexin-V positive events within a gate of 300-900nm were
      detected and defined as MPs. Our results confirmed that the characteristic
      antigens CD41/CD61 were found on platelet-derived-MPs validating our technique.
      However, for MPs derived from other cell types, we were unable to detect any
      antigen, although they were clearly expressed on the MP-producing cells in the
      contrary of several data published in the literature. Using the latex bead
      technique, we confirmed detection of CD41,61. However, the apparent expression of
      other antigens (already deemed positive in several studies) was determined to be
      false positive, indicated by negative controls (same labeling was used on MPs
      from different origins). CONCLUSION: We observed that mother cell antigens were
      not always detected on corresponding MPs by direct flow cytometry or latex bead
      cytometry. Our data highlighted that false positive results could be generated
      due to antibody aspecificity and that phenotypic characterization of MPs is a
      difficult field requiring the use of several negative controls.

PMID- 25978817
TI  - Fear conditioning induced by interpersonal conflicts in healthy individuals.
AB  - Psychophysiological markers have been focused to investigate the psychopathology
      of psychiatric disorders and personality subtypes. In order to understand
      neurobiological mechanisms underlying these conditions, fear-conditioning model
      has been widely used. However, simple aversive stimuli are too simplistic to
      understand mechanisms because most patients with psychiatric disorders are
      affected by social stressors. The objective of this study was to test the
      feasibility of a newly-designed conditioning experiment using a stimulus to cause
      interpersonal conflicts and examine associations between personality traits and
      response to that stimulus. Twenty-nine healthy individuals underwent the fear
      conditioning and extinction experiments in response to three types of stimuli: a
      simple aversive sound, disgusting pictures, and pictures of an actors' face with
      unpleasant verbal messages that were designed to cause interpersonal conflicts.
      Conditioned response was quantified by the skin conductance response (SCR).
      Correlations between the SCR changes, and personality traits measured by the
      Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised
      NEO Personality Inventory were explored. The interpersonal conflict stimulus
      resulted in successful conditioning, which was subsequently extinguished, in a
      similar manner as the other two stimuli. Moreover, a greater degree of
      conditioned response to the interpersonal conflict stimulus correlated with a
      higher ZAN-BPD total score. Fear conditioning and extinction can be successfully
      achieved, using interpersonal conflicts as a stimulus. Given that conditioned
      fear caused by the interpersonal conflicts is likely associated with borderline
      personality traits, this paradigm could contribute to further understanding of
      underlying mechanisms of interpersonal fear implicated in borderline personality
      disorder. 

PMID- 25978819
TI  - Editor's Corner: Thank You for My Wonderful Years With the Journal of Studies on
      Alcohol and Drugs.

PMID- 25978820
TI  - Personalized drinking feedback intervention for veterans of the wars in Iraq and
      Afghanistan: a randomized controlled trial.
AB  - OBJECTIVE: Research has shown that U.S. military veterans are at risk relative to
      the general adult population for excessive alcohol consumption, and veterans of
      the wars in Afghanistan and Iraq (Operation Enduring Freedom [OEF], Operation
      Iraqi Freedom [OIF], and Operation New Dawn [OND]) particularly so. The purpose
      of this study was to examine the efficacy of a brief personalized drinking
      feedback intervention tailored for veterans. METHOD: All veterans who presented
      to the OEF/OIF/OND Seamless Transition Clinic at the Harry S. Truman Memorial
      Veterans' Hospital (Columbia, MO) were eligible to participate. Participants were
      325 veterans (93% male; 82% White, 75% Army, M(age) = 32.20 years) who were
      randomly assigned to one of two conditions: personalized drinking feedback (PDF)
      or educational information (EDU). Those in the PDF condition received
      personalized information about their alcohol use, including social norms
      comparisons, risks associated with reported drinking levels, and a summary of
      their alcohol-related problems. Follow-up assessments were completed at 1 and 6
      months after intervention (response rates = 93% and 86%, respectively). RESULTS:
      Results indicated a significant (p < .05) Omnibus Group * Time effect for
      estimated peak blood alcohol concentration, although tests of simple main effects
      did not indicate between-group differences at the individual follow-up points.
      Among baseline abstainers, those in the PDF condition were more likely than those
      in the EDU condition to remain an abstainer at 6-month follow-up (p < .05).
      CONCLUSIONS: These findings provide preliminary support for the efficacy of a
      brief, inexpensive alcohol prevention/intervention for young adult military
      veterans.

PMID- 25978818
TI  - A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for
      Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via
      TLR4 Pathway.
AB  - A lipopolysaccharide from Pantoea agglomerans (LPSpa) has been applied to various
      fields for human use as a Toll-like receptor 4 ligand and its safety has been
      confirmed. Here, we showed for the first time the application of LPSpa as an
      effective mucosal adjuvant for activating vaccine-induced antigen specific immune
      responses. Mice sublingually immunized with influenza vaccine (HA split vaccine)
      with LPSpa induced both HA-specific IgG (systemic) and IgA (mucosal) antibody
      responses, which led to a significant increase in survival rate against lethal
      influenza virus challenge compared with subcutaneous vaccination. After
      sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA
      responses were induced at both mucosal surfaces close to the immunized site and
      at remote mucosal surfaces. Sublingual administration of LPSpa evoked local
      antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine
      production and the maturation and proliferation of innate immune cells via Toll
      like receptor 4 in dendritic cells. Collectively, these results suggest that
      LPSpa can be used as an effective mucosal adjuvant to stimulate and activate
      local innate immune cells to improve and enhance mucosal vaccine potency against
      various pathogens. 

PMID- 25978821
TI  - Alcohol use and caloric intake from alcohol in a national cohort of U.S. career
      firefighters.
AB  - OBJECTIVE: Both media reports and preliminary research suggest that problem
      drinking is a concern in the U.S. fire service. However, no national
      epidemiological research has been conducted. This study presents the first
      national data on alcohol consumption patterns among firefighters. METHOD: Data
      are from 954 male firefighters at 20 career fire departments. The departments
      covered 14 U.S. states, commonwealths, and/or territories and each of the four
      major U.S. Census Bureau Regions. Alcohol use was assessed through both surveys
      and, in a subsample, 24-hour dietary recall interviews from an off-duty day.
      RESULTS: More than 85% of participants consumed alcohol, nearly half reported
      excessive drinking, and approximately one third reported episodic heavy use when
      off duty. Firefighters (in comparison with officers or chiefs) and those with
      fewer years of service had particularly high levels of alcohol intake. Among
      firefighters who drank, the energy derived from alcohol averaged 539 kcals, or
      nearly 18% of total energy. Twenty five percent of firefighters consumed more
      than 770 kcals from alcohol in a single day. CONCLUSIONS: Given the high
      prevalence of excessive and episodic heavy drinking and the impact of alcohol on
      energy intake in this population, national surveillance programs and targeted
      prevention interventions for problem drinking in the U.S. fire service are
      critically needed.

PMID- 25978822
TI  - Are there secondary effects on marijuana use from brief alcohol interventions for
      college students?
AB  - OBJECTIVE: This study examined whether brief motivational interventions (BMIs)
      designed for reducing heavy drinking among college students have secondary
      effects on reducing marijuana use. METHOD: The data came from Project INTEGRATE,
      which combined data from 24 independent trials of BMIs and other individual
      focused interventions designed to reduce heavy drinking and related problems
      among college students. We analyzed data from 10 samples across nine studies that
      used random assignment of participants into either a BMI or a control group and
      assessed marijuana use outcomes (N = 6,768; 41.5% men; 73.2% White; 57.7% first
      year students; 19.2% current marijuana users at baseline). We derived three
      marijuana use groups within studies by cross-tabulating baseline and follow-up
      data: Nonusers, Reducers, and Stayers/Increasers. RESULTS: Peto's one-step odds
      ratio analyses for meta-analysis revealed no significant intervention effects on
      marijuana use at either short-term (1-3 month) or long-term (6-12 month) follow
      up. Subsequent exploratory analyses showed that those who reduced drinking were
      more likely to be a marijuana Reducer or Nonuser, compared with a
      Stayer/Increaser, at both follow-ups. CONCLUSIONS: The BMIs to reduce heavy
      drinking evaluated in this study did not reduce marijuana use. However, our
      exploratory results suggest that if we can develop interventions for college
      students that effectively reduce drinking, we may also reduce their marijuana
      use. Furthermore, as recreational use of marijuana becomes legal or
      decriminalized and marijuana becomes more readily available, it may be necessary
      to develop interventions specifically targeting marijuana use among college
      students.

PMID- 25978824
TI  - Longitudinal patterns of alcohol mixed with energy drink use among college
      students and their associations with risky drinking and problems.
AB  - OBJECTIVE: The consumption of alcohol mixed with energy drinks (AmEDs) is a form
      of risky drinking among college students, a population already in danger of heavy
      drinking and associated consequences. The goals of the current longitudinal study
      were to (a) identify types of AmED users between the first and second year of
      college and (b) examine differences among these groups in rates of highrisk
      drinking and consequences over time. METHOD: A random sample of college student
      drinkers (n = 1,710; 57.7% female) completed baseline and 6-month follow-up
      measures assessing alcohol-related behaviors. RESULTS: AmED use was endorsed by
      40% of participants during the course of the study. As anticipated, four distinct
      groups of AmED users were identified (nonusers, initiators, discontinuers, and
      continuous users) and were significantly different from one another on drinking
      and consequence outcomes. Further, significant Time * Group interaction effects
      were observed for drinking and overall consequences. Generally, across all
      outcomes and time points, nonusers reported the lowest rates of drinking and
      consequences, whereas continuous users consistently reported the highest rates of
      drinking and consequences. Students who initiated AmED use during the course of
      the study also reported anabrupt increase in alcohol use and reported
      consequences. CONCLUSIONS: Findings suggest students who consistently engage in
      and initiate AmED use also engage in riskier drinking behaviors and experience
      higher rates of consequences. Interventions that specifically target AmED use may
      be warranted and have the potential to reduce alcohol-related consequences.

PMID- 25978823
TI  - Nosologic Comparisons of DSM-IV and DSM-5 Alcohol and Drug Use Disorders: Results
      From the National Epidemiologic Survey on Alcohol and Related Conditions-III.
AB  - OBJECTIVE: The purpose of this study was to examine prevalences and concordances
      between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV), and Fifth Edition (DSM-5) substance use disorders (SUDs) in a newly
      completed U.S. epidemiologic survey. METHOD: The National Epidemiologic Survey on
      Alcohol and Related Conditions-III surveyed 36,309 civilian, noninstitutionalized
      adults. SUDs were assessed using the Alcohol Use Disorder and Associated
      Disabilities Interview Schedule-5. Concordances between DSM-IV and DSM-5
      disorders were assessed using kappa statistics. RESULTS: Prevalences of past-year
      substance-specific DSM-5 disorders (2+ criteria) were modestly higher than those
      of DSM-IV dependence and abuse combined for alcohol, sedatives/tranquilizers,
      opioids, and heroin, but lower for cannabis, cocaine, and stimulants. Lifetime
      prevalences were lower under DSM-5. Prevalences were similar between moderate to
      severe (4+ criteria) DSM-5 disorders and dependence, whereas prevalences of DSM-5
      disorders at 3+ criteria (DSM-5 [3+]) were higher, particularly for cannabis.
      Past-year concordances were excellent for DSM-IV dependence and abuse combined
      versus any DSM-5 and DSM-IV dependence versus DSM-5 moderate to severe disorders;
      lifetime concordances were fair to excellent. Past-year concordances between DSM
      IV and DSM-5 (3+) were generally similar to or modestly higher than those with
      any DSM-5 disorder; lifetime concordances were mostly lower. CONCLUSIONS:
      Findings are consistent with those informing the development of DSM-5. Future
      research should examine differences in patterns between past-year and lifetime
      disorders, particularly for cannabis. Other questions warranting investigation
      include whether different combinations of the same numbers of criteria carry
      different clinical or nosologic implications, whether changes innosology yield
      changes in treatment demand, and whether changes in characteristics of
      individuals with DSM-5 SUDs dictate modifications to screening and intervention.

PMID- 25978825
TI  - Mode of daily caffeine consumption among adolescents and the practice of mixing
      alcohol with energy drinks: relationships to drunkenness.
AB  - OBJECTIVE: Adolescent use of alcohol mixed with energy drinks (AmED) has recently
      received increased attention. Previous studies have established a strong link
      between AmED and drunkenness and suggest the importance of understanding
      associations with AmED use. In this study, we operationalized caffeine as daily
      consumption of coffee, tea, cola drinks, and energy drinks, and examined whether
      daily caffeine consumption relates to AmED use and drunkenness. METHOD: We used
      multilevel structural equation modeling (SEM) with data from the 2013 Youth in
      Iceland cross-sectional survey among students, ages 16-17 years, who attended all
      of Iceland's 31 junior colleges (N = 5,784; 75% response rate; 51% girls).
      RESULTS: Our primary model fit the data very well with a comparative fit index of
      .994 and root mean square error of approximation of .042. Of the four daily
      caffeine consumption variables, coffee had the strongest relationship with AmED
      for both girls and boys, followed by energy drink consumption. The direct
      relationship between the daily caffeine consumption variables and drunkenness was
      generally weak for both genders, but the majority of the total relationship
      between all daily caffeine consumption variables and drunkenness was attributable
      to mediation through AmED. In our primary model, AmED consumption was also very
      strongly related to drunkenness (standardized betas = .74-.79). CONCLUSIONS:
      Caffeine use among adolescents ages 16-17 years is strongly related to increased
      consumption of AmED, irrespective of mode of caffeine consumption. AmED is
      strongly and positively associated with drunkenness on both individual and school
      levels.

PMID- 25978826
TI  - Use of prescription pain medications among medical cannabis patients: comparisons
      of pain levels, functioning, and patterns of alcohol and other drug use.
AB  - OBJECTIVE: Management of chronic pain is one of the most common reasons given by
      individuals seeking medical cannabis. However, very little information exists
      about the concurrent use of cannabis and prescription pain medication (PPM). This
      study fills this gap in knowledge by systematically comparing medical cannabis
      users who use or do not use PPM, with an emphasis on understanding whether
      concurrent use of cannabis and PPM is associated with more serious forms of
      alcohol and other drug involvement. METHOD: Data from this study were collected
      from a medical cannabis clinic in southwestern Michigan (N = 273). Systematic
      comparisons were made on measures of sociodemographics, reasons for substance
      use, pain, functioning, and perceptions of PPM and medical cannabis efficacy.
      RESULTS: PPM users tended to be older and reported higher levels of pain and
      lower levels of functioning. The overall sample exhibited higher lifetime and
      past-3-month rates of alcohol and other noncannabis drug use than did the general
      population. Approximately 40% of subjects reported combining cannabis with
      alcohol, but no significant difference was observed between PPM users and
      nonusers. PPM users and nonusers did not exhibit any difference in either
      lifetime or past-3-month use of other drugs, including cocaine, sedatives, street
      opioids, and amphetamines. PPM users rated the efficacy of cannabis higher than
      PPM for pain management and indicated a strong desire to reduce PPM usage.
      CONCLUSIONS: Use of PPM among medical cannabis users was not identified as a
      correlate for more serious forms of alcohol and other drug involvement. However,
      longitudinal study designs are needed to better understand the trajectories of
      alcohol and other drug involvement over time among medical cannabis users.

PMID- 25978827
TI  - Further Analyses of Genetic Association Between GRM8 and Alcohol Dependence
      Symptoms Among Young Adults.
AB  - OBJECTIVE: The gene GRM8, a metabotropic glutamate receptor, has emerged as a
      gene of interest for its possible role in the development of alcohol dependence,
      with evidence of association with an electrophysiological endophenotype and level
      of response to alcohol as well as suggestive evidence of association with alcohol
      dependence. METHOD: The present study further investigated the association
      between GRM8 and alcohol dependence symptom counts among young adults using a new
      sample of individuals collected as part of the prospective sample (ages 18-26
      years; N = 842) from the Collaborative Study on the Genetics of Alcoholism
      (COGA). RESULTS: Two single-nucleotide polymorphisms were significantly
      associated with alcohol dependence in European Americans using the Nyholt
      corrected p value of .007: rs886003 (beta = -.212, p = .0002) and rs17862325
      (beta = -.234, p < .0001), but not in African Americans, likely because of the
      lower power to detect association in this group. CONCLUSIONS: These results
      further implicate the role of glutamate receptor genes such as GRM8 in the
      development of alcohol dependence.

PMID- 25978828
TI  - Progressive elaboration and cross-validation of a latent class typology of
      adolescent alcohol involvement in a national sample.
AB  - OBJECTIVE: Most studies of adolescent drinking focus on single alcohol use
      behaviors (e.g., high-volume drinking, drunkenness) and ignore the patterning of
      adolescents' involvement across multiple alcohol behaviors. The present latent
      class analyses (LCAs) examined a procedure for empirically determining multiple
      cut points on the alcohol use behaviors in order to establish a typology of
      adolescent alcohol involvement. METHOD: LCA was carried out on six alcohol use
      behavior indicators collected from 6,504 7th through 12th graders who
      participated in Wave I of the National Longitudinal Study of Adolescent Health
      (AddHealth). To move beyond dichotomous indicators, a "progressive elaboration"
      strategy was used, starting with six dichotomous indicators and then evaluating a
      series of models testing additional cut points on the ordinal indicators at
      progressively higher points for one indicator at a time. Analyses were performed
      on one random half-sample, and confirmatory LCAs were performed on the second
      random half-sample and in the Wave II data. RESULTS: The final model consisted of
      four latent classes (never or non-current drinkers, low-intake drinkers, non
      problem drinkers, and problem drinkers). Confirmatory LCAs in the second random
      half-sample from Wave I and in Wave II support this four-class solution. The
      means on the four latent classes were also generally ordered on an array of
      measures reflecting psychosocial risk for problem behavior. CONCLUSIONS: These
      analyses suggest that there may be four different classes or types of alcohol
      involvement among adolescents, and, more importantly, they illustrate the utility
      of the progressive elaboration strategy for moving beyond dichotomous indicators
      in latent class models.

PMID- 25978829
TI  - Personal and Perceived Peer Use of and Attitudes Toward Alcohol Among University
      and College Students in Seven EU Countries: Project SNIPE.
AB  - OBJECTIVE: The objective of this study was to explore perceptions of peer
      substance use and related attitudes among European students. Challenging
      perceptions about peer substance use has become the basis of a form of prevention
      and intervention known as the social norms approach, which can be delivered using
      personalized online feedback. This article reports baseline alcohol use and
      attitudes data for university students across Europe collected as part of the
      Social Norms Intervention for the prevention of Polydrug usE project (Project
      SNIPE). METHOD: Students from universities in Belgium, Denmark, Germany, the
      Slovak Republic, Spain, Turkey, and the United Kingdom were recruited to take
      part in an online survey by the use of email invitations, social media, classroom
      announcements, flyers, and stalls in social areas, such as in cafeterias and bars
      on campus. A total of 4,482 students agreed to participate. RESULTS: Overall,
      respondents reported both perceived alcohol use and perceived acceptance of
      alcohol use among their peers that were higher than their own use or acceptance.
      Perceived peers' behaviors and attitudes were found to be predictive of personal
      behaviors and attitudes, with some variation across countries and by sex.
      CONCLUSIONS: The results suggest that students at the participating institutions
      across selected European countries exhibit overall similar patterns of
      perceptions as have been found on American college campuses. In conjunction with
      the finding that the perceived norm is predictive of personal behavior and
      attitudes, this research provides support to the view that the social norms
      approach may be a viable method to reduce alcohol consumption among students at
      European universities.

PMID- 25978830
TI  - Socioeconomic determinants of exposure to alcohol outlets.
AB  - OBJECTIVE: Alcohol outlets tend to be located in lower income areas, exposing
      lower income populations to excess risks associated with alcohol sales through
      these establishments. The objective of this study was to test two hypotheses
      about the etiology of these differential exposures based on theories of the
      economic geography of retail markets: (a) outlets will locate within or near
      areas of high alcohol demand, and (b) outlets will be excluded from areas with
      high land and structure rents. METHOD: Data from the 2010 National Drug Strategy
      Household Survey were used to develop a surrogate for alcohol demand (i.e.,
      market potential) at two census geographies for the city of Melbourne, Australia.
      Bayesian conditional autoregressive Poisson models estimated multilevel spatial
      relationships between counts of bars, restaurants, and off-premise outlets and
      market potential, income, and zoning ordinances (Level 1: n = 8,914). RESULTS:
      Market potentials were greatest in areas with larger older age, male, English
      speaking, high-income populations. Independent of zoning characteristics, greater
      numbers of outlets appeared in areas with greater market potentials and the
      immediately surrounding areas. Greater income excluded outlets in local and
      surrounding areas. CONCLUSIONS: These findings are consistent with the hypothesis
      that alcohol outlets are located in areas with high demand and are excluded from
      high-income areas. These processes appear to take place at relatively small
      geographic scales, encourage the concentration of outlets in specific low-income
      areas, and represent a very general economic process likely to take place in
      communities throughout the world.

PMID- 25978831
TI  - The company they keep: drinking group attitudes and male bar aggression.
AB  - OBJECTIVE: The purpose of this study was to assess (a) similarities in self
      reported bar-aggression-related attitudes and behaviors among members of young
      male groups recruited on their way to bars and (b) group-level variables
      associated with individual members' self-reported likelihood of perpetrating
      physical bar aggression in the past year, controlling for individual attitudes.
      METHOD: Young, male, natural drinking groups recruited on their way to a bar
      district Thursday, Friday, and Saturday nights (n = 167, 53 groups) completed an
      online survey that measured whether they had perpetrated physical aggression at a
      bar in the past year and constructs associated with bar aggression, including
      attitudes toward male bar aggression and frequency of heavy episodic drinking in
      the past year. RESULTS: Intraclass correlations and chi-square tests demonstrated
      significant within-group similarity on bar-aggression-related attitudes and
      behaviors (ps < .01). Hierarchical linear modeling revealed that group attitudes
      toward bar aggression were significantly associated with individuals' likelihood
      of perpetrating physical bar aggression, controlling for individual attitudes (p
      < .01); however, the link between group heavy episodic drinking and self-reported
      bar aggression was nonsignificant in the full model. CONCLUSIONS: This study
      suggests that the most important group influence on young men's bar aggression is
      the attitudes of other group members. These attitudes were associated with group
      members' likelihood of engaging in bar aggression over and above individuals' own
      attitudes. A better understanding of how group attitudes and behavior affect the
      behavior of individual group members is needed to inform aggression-prevention
      programming.

PMID- 25978832
TI  - Alcohol expectancies and alcohol outcomes: effects of the use of protective
      behavioral strategies.
AB  - OBJECTIVE: Alcohol expectancies (AEs) are positively associated with drinking
      behaviors, whereas the use of protective behavioural strategies (PBS) is
      negatively related to alcohol outcomes among young adults. PBS have been shown to
      weaken relationships between some alcohol risk factors and alcohol outcomes. This
      study aimed to examine longitudinally the moderating effect of PBS on the
      relationships between AEs and alcohol outcomes among young adults. METHOD:
      Participants (N = 188; 61.7% female) were U.S. young adults participating in a
      larger longitudinal study. Measures of PBS, AEs, alcohol use, and related
      consequences were used from the baseline and 12-month follow-up assessments.
      RESULTS: Negative binomial hurdle models found that PBS (total score)
      significantly moderated the relationship between positive AEs and consequences,
      such that among high school seniors endorsing higher positive AEs, those using
      more PBS in high school reported fewer negative consequences 1 year later. PBS
      (Manner of Drinking) also moderated the relationship between negative AEs and
      alcohol use, revealing the use of PBS in high school as having a protective
      function against later drinking among participants with high positive AEs. Last,
      PBS (Serious Harm Reduction) significantly moderated the associations between
      positive AEs and alcohol use and between negative AEs and consequences, such that
      participants with higher AEs and higher PBS use in high school were at greatest
      risk for drinking and experiencing negative consequences later. CONCLUSIONS:
      Overall, these findings suggest that PBS use may be protective by weakening
      relationships between positive AEs and alcohol outcomes. Limitations and future
      directions are discussed.

PMID- 25978833
TI  - Sexual assault history and its association with the use of drinking protective
      behavioral strategies among college women.
AB  - OBJECTIVE: The current study examined the relationship between sexual assault
      history and drinking protective behavioral strategies (PBS). Given the
      relationship between sexual assault history and alcohol use, we hypothesized that
      after we controlled for drinking behavior, women with a childhood sexual abuse
      (CSA) history would use fewer drinking PBS than those without a CSA history. We
      also hypothesized that a history of adolescent/adult sexual assault (ASA)
      involving incapacitation and force would be associated with lower use of drinking
      PBS after controlling for CSA history and drinking behavior. METHOD: A total of
      800 undergraduate college women completed a survey online. RESULTS: Regression
      analyses indicated that the only sexual assault history type that was
      consistently related to all three types of drinking PBS was ASA involving
      incapacitation. Women with a history of incapacitated ASA were less likely to use
      any type of drinking PBS than women without such history. A history of other
      types of sexual assault (CSA, physically forced ASA, and verbally coerced ASA)
      was associated only with lower use of serious harm-reduction drinking PBS, such
      as going home with a friend or knowing the location of your drink. CONCLUSIONS:
      This was the first study to examine the relationship between different sexual
      assault histories and drinking PBS, and it furthers our understanding of the
      relationship between alcohol and sexual assault. Possible reasons for this
      relationship between ASA and PBS use are discussed.

PMID- 25978834
TI  - A prospective study of stressful events, coping motives for drinking, and alcohol
      use among middle-aged adults.
AB  - OBJECTIVE: This prospective study investigated moderator variable models of the
      interrelationships among stressful events, coping motives for drinking, and
      current alcohol use on subsequent alcohol use across a 5-year window with middle
      aged adults. METHOD: Data from women (n = 716; M(age) = 55.29 years at baseline)
      and men (n = 505; M(age) = 57.57 years at baseline) were used to examine theory
      guided hypotheses that current levels of alcohol use would interact with
      stressful events and coping motives for drinking to predict higher levels of
      alcohol use across time. Analyses were conducted separately for men and women.
      RESULTS: After we controlled for several potentially important covariates (i.e.,
      age, educational level, family income, and marital status), prospective
      regression analyses supported moderator effects for current alcohol use and
      stressful events as predictors of changes in alcohol use, and a somewhat weaker
      consistency of moderator effects for current alcohol use and coping motives for
      drinking as predictors of changes in alcohol use. For example, higher levels of
      baseline alcohol involvement in conjunction with higher levels of stress
      predicted higher levels of alcohol use and alcohol problems 5 years later.
      Similarly, higher levels of coping motives and higher levels of heavy episodic
      drinking predicted higher levels of heavy episodic drinking among women 5 years
      later. CONCLUSIONS: The findings were discussed from an alcohol-stress
      vulnerability model of affect regulation and a positive regulatory feedback loop
      perspective wherein conditional relationships among baseline alcohol use
      indicators, stressful events, and coping drinking motives predicted greater
      alcohol involvement, especially problematic use, across time.

PMID- 25978835
TI  - Alcohol use to facilitate a suicide attempt: an event-based examination.
AB  - OBJECTIVE: The current study is based on the hypothesis that alcohol-involved
      suicide attempts are characterized by lower premeditation and intent, but only
      when the use of alcohol is not motivated by the desire to facilitate the attempt.
      Test of this idea was conducted by comparing proximal suicide premeditation and
      intent of suicide attempts among three groups: individuals who (a) drank to
      facilitate the attempt (e.g., to "numb fears" about attempting), (b) drank for
      nonfacilitative motives, and (c) did not use alcohol before the attempt. METHOD:
      Participants included 324 (62% female) recent suicide attempters presenting to a
      Level 1 trauma hospital. The Timeline Followback Interview for Suicide Attempts
      and a novel Suicide Facilitative Drinking Motives Scale were used to assess
      facilitative motives for drinking and characteristics of the attempt. RESULTS:
      One third of participants drank before the attempt, and most (73%) who used
      alcohol did not do so to facilitate the attempt. As hypothesized, attempts
      carried out by this group had shorter proximal suicide premeditation and lower
      suicide intent compared with the other study groups; in contrast, individuals who
      drank to facilitate the attempt were similar to non-alcohol users on these
      indices. CONCLUSIONS: Alcohol-involved suicide attempts are heterogeneous.
      Motives for drinking are a key source of heterogeneity insofar as fundamental
      characteristics of attempts (proximal premeditation, intent) differ as a function
      of drinking motivation. Clinical implications include that individuals making
      suicide attempts with facilitative motives for drinking cannot be assumed to be
      at lowered risk upon a drop in blood alcohol level.

PMID- 25978836
TI  - Gender differences in the roles of religion and locus of control on alcohol use
      and smoking among African Americans.
AB  - OBJECTIVE: Spiritual health locus of control reflects a person's beliefs about
      the role of a higher power in one's health and can take an active or a passive
      perspective. The purpose of this study was to examine the moderating role of
      active and passive spiritual health locus of control beliefs on select health
      risk behaviors--alcohol use and smoking--in a national sample of African
      Americans. METHOD: A national U.S. probability sample of study participants (N =
      2,370; 906 men; 1,464 women) completed a telephone survey assessing religious
      involvement, active and passive spiritual health locus of control beliefs, and
      alcohol consumption and smoking status. Because of previous research suggesting
      gender-specific associations among these variables, moderation analyses were
      conducted separately for men and women. RESULTS: For women, higher religious
      behaviors were associated with less alcohol use, and this effect was more
      pronounced among those high in active spiritual health locus of control. For men,
      the combination of lower religious beliefs and higher passive spiritual health
      locus of control was associated with more alcohol consumption and more days of
      consuming five or more alcoholic drinks. No moderation effects were found for
      smoking. CONCLUSIONS: This study identified unique patterns of religious
      involvement and spiritual health locus of control beliefs that are associated
      with alcohol use, including heavy drinking, among African Americans. These
      findings have implications for pastoral counseling and other faith-based
      approaches for addressing heavy drinking in African Americans.

PMID- 25978837
TI  - Alcohol-induced impairment in adolescents admitted to inpatient treatment after
      heavy episodic drinking: effects of age and gender.
AB  - OBJECTIVE: In Germany and many other countries, the number of adolescent heavy
      episodic drinking-induced hospital admissions (HEDHA) in pediatric units markedly
      increased during the past decade. A low level of response to alcohol in young
      adults is associated with high risk for later development of alcohol use
      disorders (AUDs). METHOD: We performed a retrospective chart review of all 1,123
      HEDHA cases in adolescents aged 11-17 years who were admitted to one of the
      pediatric inpatient units covering the cities of Dresden, Pirna, and Rostock,
      Germany, between 2000 and 2008. Blood alcohol concentration (BAC) and Glasgow
      Coma Scale (GCS) measures on admission were documented in 846 cases. RESULTS: The
      mean (SD) BAC was 155 (50) mg/100 ml full blood, and M (SD) GCS was 12.21 (3.02).
      These parameters were negatively correlated with each other (r = -.256, p <
      .001), indicating more impairment at higher BACs. To describe a numerical
      estimate of how severely a subject was compromised relative to his BAC, the GCS
      scores were inverted (making high scores indicate severe impairment) and divided
      by BAC. The resulting alcohol-induced impairment index (AIII) was significantly
      influenced by an interaction between age and gender, decreasing with age in boys
      but increasing in girls. CONCLUSIONS: During adolescence, alcohol-induced
      impairment develops differently in boys and girls, which may be because of the
      girls' developmental edge. The high variability of observed AIII might help to
      predict the risk for later AUDs in the emergency department, simply by measuring
      BAC and GCS.

PMID- 25978840
TI  - Abstracts of Papers Presented at the 2014 Annual Meeting of the Society for
      Technology in Anesthesia (STA), January 15-18, 2014.

PMID- 25978839
TI  - Clinical characteristics and risk factors of pyogenic spondylitis caused by gram
      negative bacteria.
AB  - BACKGROUND: There are limited data describing the clinical characteristics of
      pyogenic spondylitis caused by Gram-negative bacteria (GNB). The aim of this
      study was to investigate the predisposing factors and clinical characteristics of
      pyogenic spondylitis caused by GNB compared to Gram-positive cocci (GPC).
      METHODS: We performed a retrospective review of medical records from patients
      with culture-confirmed pyogenic spondylitis at four tertiary teaching hospitals
      over an 8-year period. RESULTS: A total of 344 patients with culture-confirmed
      pyogenic spondylitis were evaluated. There were 62 patients (18.0%) with pyogenic
      spondylitis caused by GNB and the most common organism was Escherichia coli (n =
      35, 10.2%), followed by Pseudomonas aeruginosa (n = 10, 2.9%). Pyogenic
      spondylitis caused by GNB was more frequently associated with the female gender
      (64.5 vs. 35.5%, P <0.01), preexisting or synchronous genitourinary tract
      infection (32.3 vs. 2.1%, P< 0.01), and intra-abdominal infection (12.9 vs. 0.4%,
      P< 0.01) compared to patients with GPC. Although pyogenic spondylitis caused by
      GNB presented with severe sepsis more frequently (24.2 vs. 11.3%, P = 0.01), the
      mortality rate (6.0 vs. 5.2%) and the proportion of patients with residual
      disability (6.0 vs. 9.0%), defined as grade 3 or 4 (P = 0.78) 3 months after
      completion of treatment, were not significantly different compared to GPC
      patients. CONCLUSION: GNB should be considered as the etiologic organism when
      infectious spondylitis develops in a patient with preexisting or synchronous
      genitourinary tract and intra-abdominal infection. In addition, the mortality
      rate and clinical outcomes are not significantly different between pyogenic
      spondylitis caused by GNB and GPC.

PMID- 25978838
TI  - Genome-Wide Transcriptional Profiling of Clostridium perfringens SM101 during
      Sporulation Extends the Core of Putative Sporulation Genes and Genes Determining
      Spore Properties and Germination Characteristics.
AB  - The formation of bacterial spores is a highly regulated process and the ultimate
      properties of the spores are determined during sporulation and subsequent
      maturation. A wide variety of genes that are expressed during sporulation
      determine spore properties such as resistance to heat and other adverse
      environmental conditions, dormancy and germination responses. In this study we
      characterized the sporulation phases of C. perfringens enterotoxic strain SM101
      based on morphological characteristics, biomass accumulation (OD600), the total
      viable counts of cells plus spores, the viable count of heat resistant spores
      alone, the pH of the supernatant, enterotoxin production and dipicolinic acid
      accumulation. Subsequently, whole-genome expression profiling during key phases
      of the sporulation process was performed using DNA microarrays, and genes were
      clustered based on their time-course expression profiles during sporulation. The
      majority of previously characterized C. perfringens germination genes showed
      upregulated expression profiles in time during sporulation and belonged to two
      main clusters of genes. These clusters with up-regulated genes contained a large
      number of C. perfringens genes which are homologs of Bacillus genes with roles in
      sporulation and germination; this study therefore suggests that those homologs
      are functional in C. perfringens. A comprehensive homology search revealed that
      approximately half of the upregulated genes in the two clusters are conserved
      within a broad range of sporeforming Firmicutes. Another 30% of upregulated genes
      in the two clusters were found only in Clostridium species, while the remaining
      20% appeared to be specific for C. perfringens. These newly identified genes may
      add to the repertoire of genes with roles in sporulation and determining spore
      properties including germination behavior. Their exact roles remain to be
      elucidated in future studies. 

PMID- 25978842
TI  - Impact of Respiratory Morbidities on Neurodevelopmental Outcome of Late Preterm
      Infants.
AB  - OBJECTIVE: This study aims to evaluate impact of respiratory and other neonatal
      comorbidities on neurodevelopmental outcome in late preterm infants (LPT).
      METHOD: Retrospective study of LPT infants (34 (0/7)-36 (6/7) weeks' gestation)
      discharged from the New York University Langone Medical Center neonatal intensive
      care unit, during January 2006 to December 2010 and received follow-up care up to
      2 years of age. Neonatal morbidities were correlated with neurodevelopmental
      outcomes and assessed by performance on the Mullen Scales of Early Learning
      during three developmental follow-up visits. RESULTS: A total of 99 LPT completed
      neurodevelopmental assessment up to 2 years of age. Infants with diagnosis of
      moderate-to-severe respiratory distress syndrome showed a significantly lower
      performance in the visual reception on the second (p<0.01) and third visit
      (p=0.02), as well as lower performance in the receptive language (visit 2,
      p=0.02; visit 3, p<0.01). A diagnosis of persistent pulmonary hypertension was
      found to be associated with significantly lower performance in the visual
      reception at all visits (p<0.01; p=0.02; p=0.02) and in the receptive language on
      the second and third visit (p=0.03; p=0.02). Combined respiratory morbidities
      were also associated with lower developmental scores in fine motor (visit 2,
      p<0.01; visit 3, p=0.04) as well as expressive language (visit 3, p=0.02).
      CONCLUSION: LPT with significant respiratory morbidities are at higher risk for
      long-term developmental delays, mainly affecting cognitive developmental domains.

PMID- 25978841
TI  - Association between Gastroenterological Malignancy and Diabetes Mellitus and Anti
      Diabetic Therapy: A Nationwide, Population-Based Cohort Study.
AB  - BACKGROUND: The relationship between diabetes mellitus (DM) and cancer incidence
      has been evaluated in limited kinds of cancer. The effect of anti-diabetic
      therapy (ADT) on carcinogenesis among diabetic patients is also unclear.
      MATERIALS AND METHODS: Using population-based representative insurance claims
      data in Taiwan, 36,270 DM patients and 145,080 comparison subjects without DM
      were identified from claims from 2005 to 2010. The association between the top
      ten leading causes of cancer-related death in Taiwan and DM was evaluated.
      Whether ADT altered the risk of developing cancer was also investigated. RESULTS:
      Incidence of cancer at any site was significantly higher in patients with DM than
      in those without (p<0.001). The risk of carcinogenesis imparted by DM was
      greatest in gastroenterological malignancies (liver, pancreas, and colorectal
      cancer) as well as lung, breast and oral cancer (p<0.001). Among the oral types
      of ADT, metformin decreased the risk of lung and liver cancer, but had less
      effect on reducing the risk of colorectal cancer. alpha-glucosidase inhibitor
      decreased the risk of developing liver, colorectal, and breast cancer. Apart from
      intermediate-acting insulin, rapid-acting, long-acting, and combination insulin
      treatment significantly reduced the overall cancer risk among all DM patients. In
      subgroup analysis, long-acting insulin treatment significantly decreased the risk
      of lung, liver, and colorectal cancer. CONCLUSION: Our results supported the
      notion that pre-existing DM increases the incidence of gastroenterological
      cancer. ADT, especially metformin, alpha-glucosidase inhibitor, and long-acting
      insulin treatment, may protect patients with DM against these malignancies. It is
      crucial that oncologists should closely collaborate with endocrinologists to
      provide an optimal cancer-specific therapy and diabetic treatment to patients
      simultaneously with cancer and DM.

PMID- 25978843
TI  - A fluorescence study of isofagomine protonation in beta-glucosidase.
AB  - N-(10-Chloro-9-anthracenemethyl)isofagomine 5 and N-(10-chloro-9
      anthracenemethyl)-1-deoxynojirimycin 6 were prepared, and their inhibition of
      almond beta-glucosidase was measured. The isofagomine derivative 5 was found to
      be a potent inhibitor, while the 1-deoxynojirimycin derivative 6 displayed no
      inhibition at the concentrations investigated. Fluorescence spectroscopy of 5
      with almond beta-glucosidase at different pH values showed that the inhibitor
      nitrogen is not protonated when bound to the enzyme. Analysis of pH inhibition
      data confirmed that 5 binds as the amine to the enzyme's unprotonated
      dicarboxylate form. This is a radically different binding mode than has been
      observed with isofagomine and other iminosugars in the literature. 

PMID- 25978845
TI  - Lamellar sheet exfoliation of single lipid vesicles by a membrane-active peptide.
AB  - Using total internal fluorescence microscopy, highly parallel measurements of
      single lipid vesicles unexpectedly reveal that a small fraction of vesicles
      rupture in multiple discrete steps when destabilized by a membrane-active peptide
      which is in contrast to classical solubilization models. To account for this
      surprizing kinetic behaviour, we identified that this vesicle subpopulation
      consists of multilamellar vesicles, and that the outermost lamella is more
      susceptible to rupture than unilamellar vesicles of even smaller size. This
      finding sheds light on the multiple ways in which membrane configuration can
      influence strain in the bilayer leaflet and contribute to nm-scale membrane
      curvature sensing. 

PMID- 25978844
TI  - Specific Mechanisms Underlying Right Heart Failure: The Missing Upregulation of
      Superoxide Dismutase-2 and Its Decisive Role in Antioxidative Defense.
AB  - AIMS: Research into right ventricular (RV) physiology and identification of
      pathomechanisms underlying RV failure have been neglected for many years, because
      function of the RV is often considered less important for overall hemodynamics
      and maintenance of blood circulation. In view of this, this study focuses on
      identifying specific adaptive mechanisms of the RV and left ventricle (LV) during
      a state of chronic nitric oxide (NO) deficiency, one of the main causes of
      cardiac failure. NO deficiency was induced in rats by L-NAME feeding over a 4
      week period. The cardiac remodeling was then characterized separately for the
      RV/LV using quantitative real-time polymerase chain reaction, histology, and
      functional measurements. RESULTS: Only the RV underwent remodeling that
      corresponded morphologically and functionally with the pattern of dilated
      cardiomyopathy. Symptoms in the LV were subtle and consisted primarily of
      moderate hypertrophy. A massive increase in reactive oxygen species (ROS) (+4.5+/
      0.8-fold, vs. control) and a higher degree of oxidized tropomyosin (+46%+/-4% vs.
      control) and peroxynitrite (+32%+/-2% vs. control) could be identified as the
      cause of both RV fibrosis and contractile dysfunction. The expression of
      superoxide dismutase-2 was specifically increased in the LV by 51%+/-3% and
      prevented the ROS increase and the corresponding structural and functional
      remodeling. INNOVATION: This study identified the inability of the RV to increase
      its antioxidant capacity as an important risk factor for developing RV failure.
      CONCLUSION: Unlike the LV, the RV did not display the necessary adaptive
      mechanisms to cope with increased oxidative stress during a state of chronic NO
      deficiency.

PMID- 25978847
TI  - Leigh syndrome: neuropathology and pathogenesis.
AB  - Leigh syndrome (LS) is the most common pediatric presentation of a defined
      mitochondrial disease. This progressive encephalopathy is characterized
      pathologically by the development of bilateral symmetrical lesions in the
      brainstem and basal ganglia that show gliosis, vacuolation, capillary
      proliferation, relative neuronal preservation, and by hyperlacticacidemia in the
      blood and/or cerebrospinal fluid. Understanding the molecular mechanisms
      underlying this unique pathology has been challenging, particularly in view of
      the heterogeneous and not yet fully determined genetic basis of LS. Moreover,
      animal models that mimic features of LS have only been created relatively
      recently. Here, we review the pathology of LS and consider what might be the
      molecular mechanisms underlying its pathogenesis. Data from a wide range of
      sources, including patient samples, animal models, and studies of hypoxic
      ischemic encephalopathy (a condition that shares features with LS), were used to
      provide insight into the pathogenic mechanisms that may drive lesion development.
      Based on current data, we suggest that severe ATP depletion, gliosis,
      hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity
      cumulatively contribute to the neuropathogenesis of LS. An intimate understanding
      of the molecular mechanisms causing LS is required to accelerate the development
      of LS treatments. 

PMID- 25978848
TI  - Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a
      Huntington disease mouse model.
AB  - Glucose metabolism is reduced in the brains of patients with Huntington disease
      (HD). The mechanisms underlying this deficit, its link to the pathology of the
      disease, and the vulnerability of the striatum in HD remain unknown.
      Abnormalities in some of the key mitochondrial enzymes involved in glucose
      metabolism, including the pyruvate dehydrogenase complex (PDHC) and the
      tricarboxylic acid (TCA) cycle, may contribute to these deficits. Here,
      activities for these enzymes and select protein levels were measured in human
      postmortem cortex and in striatum and cortex of an HD mouse model (Q175); mRNA
      levels encoding for these enzymes were also measured in the Q175 mouse cortex.
      The activities of PDHC and nearly all of the TCA cycle enzymes were dramatically
      lower (-50% to 90%) in humans than in mice. The activity of succinate
      dehydrogenase increased with HD in human (35%) and mouse (23%) cortex. No other
      changes were detected in the human HD cortex or mouse striatum. In Q175 cortex,
      there were increased activities of PDHC (+12%) and aconitase (+32%). Increased
      mRNA levels for succinyl thiokinase (+88%) and isocitrate dehydrogenase (+64%)
      suggested an upregulation of the TCA cycle. These patterns of change differ from
      those reported in other diseases, which may offer unique metabolic therapeutic
      opportunities for HD patients. 

PMID- 25978850
TI  - The First Neuropathological Studies on HDLS.

PMID- 25978849
TI  - Activation of the Unfolded Protein Response in Sporadic Inclusion-Body Myositis
      but Not in Hereditary GNE Inclusion-Body Myopathy.
AB  - Muscle fibers in patients with sporadic inclusion-body myositis (s-IBM),the most
      common age-associated myopathy, are characterized by autophagic vacuoles and
      accumulation of ubiquitinated and congophilic multiprotein aggregates that
      contain amyloid-beta and phosphorylated tau. Muscle fibers of autosomal-recessive
      hereditary inclusion-body myopathy caused by the GNE mutation (GNE-h-IBM) display
      similar pathologic features, except with less pronounced congophilia.
      Accumulation of unfolded/misfolded proteins inside the endoplasmic reticulum (ER)
      lumen leads to ER stress, which elicits the unfolded protein response (UPR) as a
      protective mechanism. Here we demonstrate for the first time that UPR is
      activated in s-IBM muscle biopsies, since there was 1) increased activating
      transcription factor 4 (ATF4) protein and increased mRNA of its target C/EBP
      homologous protein; 2) cleavage of the ATF6 and increased mRNA of its target
      glucose-regulated protein 78; and 3) an increase of the spliced form of X-box
      binding protein 1 and increased mRNA of ER degradation-enhancing alpha
      mannosidase-like protein, target of heterodimer of cleaved ATF6 and spliced X-box
      binding protein 1. In contrast, we did not find similar evidence of the UPR
      induction in GNE-h-IBM patient muscle, suggesting that different intracellular
      mechanisms might lead to similar pathologic phenotypes. Interestingly, cultured
      GNE-h-IBM muscle fibers had a robust UPR response to experimental ER stress
      stimuli, suggesting that the GNE mutation per se is not responsible for the lack
      of UPR in GNE-h-IBM biopsied muscle. 

PMID- 25978851
TI  - Artesunate down-regulates immunosuppression from colorectal cancer Colon26 and
      RKO cells in vitro by decreasing transforming growth factor beta1 and interleukin
      10.
AB  - Immunosuppression is the main source of ineffective treatment on tumor, and the
      study aimed to investigate the effect of artesunate on tumor immunosuppression.
      Supernatants of re-cultivated murine colorectal cancer cell Colon26 and human
      colorectal cancer cell RKO after pre-treatment with or without artesunate were
      enrolled, and their effects on five immune parameters were assessed, including
      killing activity of natural killer (NK) and lymphocyte proliferation, as measured
      by MTT, and expressions of interleukin 2 receptor (IL-2R)alpha,
      CD3epsilon(+)zeta(+) and CD3epsilon(-)zeta(+) on lymphocytes, as analyzed by flow
      cytometry. Six immunosuppressive factors were measured by ELISA, including
      transforming growth factor (TGF) beta1, vascular endothelial growth factor
      (VEGF), IL-4, IL-6, IL-10, and prostaglandin E2 (PGE2). Then, multiple linear
      regression analysis was applied to reveal the correlation between
      immunosuppression and immunosuppressive factors, and was used to confirm the
      findings. It was shown that Colon26 and RKO cells secreted immunosuppressive
      factors and inhibited these five immune parameters steadily. After pretreatment
      with artesunate, immunosuppression from the two cells was down-regulated
      significantly (all P<0.05), and the concentrations of TGF-beta1 and IL-10
      decreased greatly (all P<0.001). There were positive correlations between the
      down-regulation of immunosuppression and the decrease in TGF-beta1 or IL-10.
      Their combined potency attributed to decreased TGF-beta1 and IL-10 with respect
      to the down-regulating effect of artesunate on immunosuppression of NK killing,
      lymphocyte proliferation and expressions of IL-2Ralpha and CD3epsilon(+)zeta(+),
      was about 60%-90%. The present analysis provides clues that artesunate reverses
      the immunosuppression from Colon26 and RKO colorectal cancer cells by decreasing
      TGF-beta1 and IL-10. This is probably one of the anti-tumor mechanisms of
      artesunate. 

PMID- 25978853
TI  - Batch dark fermentation from enzymatic hydrolyzed food waste for hydrogen
      production.
AB  - A combination bioprocess of solid-state fermentation (SSF) and dark fermentative
      hydrogen production from food waste was developed. Aspergillus awamori and
      Aspergillus oryzae were utilized in SSF from food waste to generate glucoamylase
      and protease which were used to hydrolyze the food waste suspension to get the
      nutrients-rich (glucose and free amino nitrogen (FAN)) hydrolysate. Both glucose
      and FAN increased with increasing of food waste mass ratio from 4% to 10% (w/v)
      and the highest glucose (36.9 g/L) and FAN (361.3mg/L) were observed at food
      waste mass ratio of 10%. The food waste hydrolysates were then used as the
      feedstock for dark fermentative hydrogen production by heat pretreated sludge.
      The best hydrogen yield of 39.14 ml H2/g food waste (219.91 ml H2/VSadded) was
      achieved at food waste mass ratio of 4%. The proposed combination bioprocess
      could effectively accelerate the hydrolysis rate, improve raw material
      utilization and enhance hydrogen yield.

PMID- 25978852
TI  - Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A
      Randomized Controlled Trial.
AB  - BACKGROUND: The World Health Organization estimates that > 140 million people
      worldwide are exposed to arsenic (As)-contaminated drinking water. As undergoes
      biologic methylation, which facilitates renal As elimination. In folate-deficient
      individuals, this process is augmented by folic acid (FA) supplementation,
      thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust
      predictor of As methylation patterns. Although the reasons for this are unclear,
      creatine synthesis is a major consumer of methyl donors, and this synthesis is
      down-regulated by dietary/supplemental creatine. OBJECTIVES: Our aim was to
      determine whether 400 or 800 MUg FA and/or creatine supplementation lowers bAs in
      an As-exposed Bangladeshi population. METHODS: We conducted a clinical trial in
      which 622 participants were randomized to receive 400 MUg FA, 800 MUg FA, 3 g
      creatine, 3 g creatine+400 MUg FA, or placebo daily. All participants received an
      As-removal filter on enrollment, and were followed for 24 weeks. After the 12th
      week, half of the two FA groups were switched to placebo to evaluate post
      treatment bAs patterns. RESULTS: Linear models with repeated measures indicated
      that the decline in ln(bAs) from baseline in the 800-MUg FA group exceeded that
      of the placebo group (weeks 1-12: beta= -0.09, 95% CI: -0.18, -0.01; weeks 13-24:
      FA continued: beta= -0.12, 95% CI: -0.24, -0.00; FA switched to placebo: beta= 
      0.14, 95% CI: -0.26, -0.02). There was no rebound in bAs related to cessation of
      FA supplementation. Declines in bAs observed in the remaining treatment arms were
      not significantly different from those of the placebo group. CONCLUSIONS: In this
      mixed folate-deficient/replete study population, 12- and 24-week treatment with
      800 MUg (but not 400 MUg) FA lowered bAs to a greater extent than placebo; this
      was sustained 12 weeks after FA cessation. In future studies, we will evaluate
      whether FA and/or creatine altered As methylation profiles.

PMID- 25978854
TI  - Selection of forward osmosis draw solutes for subsequent integration with
      anaerobic treatment to facilitate resource recovery from wastewater.
AB  - Forward osmosis (FO) can be used to extract clean water and pre-concentrate
      municipal wastewater to make it amenable to anaerobic treatment. A protocol was
      developed to assess the suitability of FO draw solutes for pre-concentrating
      wastewater for potential integration with anaerobic treatment to facilitate
      resource recovery from wastewater. Draw solutes were evaluated in terms of their
      ability to induce osmotic pressure, water flux, and reverse solute flux. The
      compatibility of each draw solute with subsequent anaerobic treatment was
      assessed by biomethane potential analysis. The effect of each draw solute (at
      concentrations corresponding to the reverse solute flux at ten-fold pre
      concentration of wastewater) on methane production was also evaluated. The
      results show that ionic organic draw solutes (e.g., sodium acetate) were most
      suitable for FO application and subsequent anaerobic treatment. On the other
      hand, the reverse solute flux of inorganic draw solutions could inhibit methane
      production from FO pre-concentrated wastewater. 

PMID- 25978855
TI  - Microbial community succession mechanism coupling with adaptive evolution of
      adsorption performance in chalcopyrite bioleaching.
AB  - The community succession mechanism of Acidithiobacillus sp. coupling with
      adaptive evolution of adsorption performance were systematically investigated.
      Specifically, the MUmax of attached and free cells was increased and peak time
      was moved ahead, indicating both cell growth of Acidithiobacillus ferrooxidans
      and Acidithiobacillus thiooxidans was promoted. In the mixed strains system, the
      domination courses of A. thiooxidans was dramatically shortened from 22th day to
      15th day, although community structure finally approached to the normal system.
      Compared to A. ferrooxidans, more positive effects of adaptive evolution on cell
      growth of A. thiooxidans were shown in either single or mixed strains system.
      Moreover, higher concentrations of sulfate and ferric ions indicated that both
      sulfur and iron metabolism was enhanced, especially of A. thiooxidans.
      Consistently, copper ion production was improved from 65.5 to 88.5 mg/L. This new
      adaptive evolution and community succession mechanism may be useful for guiding
      similar bioleaching processes.

PMID- 25978856
TI  - Use of a mannitol rich ensiled grass press juice (EGPJ) as a sole carbon source
      for polyhydroxyalkanoates (PHAs) production through high cell density
      cultivation.
AB  - This study demonstrates the use of a mannitol rich ensiled grass press juice
      (EGPJ) as a renewable carbon substrate for polyhydroxyalkanoates (PHA) production
      in shaking flask experiments and fed-batch stirred tank reactor cultivations. Fed
      batch cultivations of Burkholderia sacchari IPT101 using EGPJ as sole carbon
      source produced 44.5 g/L CDW containing 33% polyhydroxybutyrate (PHB) in 36 h,
      while Pseudomonas chlororaphis IMD555 produced a CDW of 37 g/L containing 10% of
      medium chain length polyhydroxyalkanoates (mcl-PHA) in 34 h. PHB and mcl-PHA
      extracted from B. sacchari IPT101 and P. chlororaphis IMD555, grown on EGPJ, had
      a molecular weight of 548 kg/mol and 115.4 kg/mol, respectively. While mcl-PHA
      can be produced from EGPJ, PHB production is more interesting as there is a 4
      fold higher volumetric productivity compared to mcl-PHA.

PMID- 25978857
TI  - Longitudinal changes in gestational weight gain and the association with
      intrauterine fetal growth.
AB  - OBJECTIVE: Total pregnancy weight gain has been associated with infant
      birthweight; however, most prior studies lacked repeat ultrasound measurements.
      Understanding of the longitudinal changes in maternal weight gain and
      intrauterine changes in fetal anthropometrics is limited. STUDY DESIGN:
      Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for
      delivering small-for-gestational-age (SGA) were analyzed. Women had >=1 (median
      12) antenatal weight measurements. Ultrasounds were targeted at 17, 25, 33, and
      37 weeks of gestation. Analyses involved a multi-step process. First,
      trajectories were estimated across gestation for maternal weight gain and fetal
      biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm),
      femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed
      models. Second, the association between maternal weight changes (per 5 kg) and
      corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was
      estimated for each fetal parameter adjusting for prepregnancy body mass index,
      height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to
      the respective period as applicable. Third, the probability of fetal SGA, EFW
      <10th percentile, at the 3rd ultrasound was estimated across the spectrum of
      maternal weight gain rate by SGA status at the 2nd ultrasound. RESULTS: From 0 to
      17 weeks, changes in maternal weight were most strongly associated with changes
      in BPD [beta=0.51 per 5 kg (95%CI 0.26, 0.76)] and FL [beta=0.46 per 5 kg (95%CI
      0.26, 0.65)]. From 17 to 28 weeks, AC [beta=2.92 per 5 kg (95%CI 1.62, 4.22)] and
      EFW [beta=58.7 per 5 kg (95%CI 29.5, 88.0)] were more strongly associated with
      changes in maternal weight. Increased maternal weight gain was significantly
      associated with a reduced probability of intrauterine SGA; for a normal weight
      woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight
      gain rate of 0.29 kg/w (10th percentile) was 59%, compared to 38% with a rate of
      0.67 kg/w (90th percentile). CONCLUSION: Among women at high-risk for SGA,
      maternal weight gain was associated with fetal growth throughout pregnancy, but
      had a differential relationship with specific biometrics across gestation. For
      women with fetal SGA identified mid-pregnancy, increased antenatal weight gain
      was associated with a decreased probability of fetal SGA approximately 7 weeks
      later.

PMID- 25978858
TI  - A prospective comparative study of cosmetic satisfaction for three different
      surgical approaches.
AB  - OBJECTIVES: To compare gynecologic patients' cosmetic satisfaction with surgical
      wounds after different approaches: laparoendoscopic single-site surgery (LESS),
      conventional laparoscopic surgery (CLS) and open surgery (OS). STUDY DESIGN: This
      was a prospective study. The primary outcome was the cosmetic satisfaction after
      LESS, CLS, or OS, measured at 1 and 6 months post-surgery using the well
      validated Cosmetic Scale. Multiple linear regression analysis was used to
      determine whether the surgical approach was independently associated with
      cosmetic satisfaction or not. RESULTS: Of 294 patients enrolled, 84 (28.6%), 129
      (43.9%), and 81 patients (27.3%) underwent LESS, CLS, and OS, respectively.
      Cosmetic Scale scores in the LESS group at 1 month post-surgery was about 7
      higher than in the CLS group and 9 higher than in the OS group (P<0.001). This
      difference was maintained also at 6 months post-surgery (P<0.001). On multiple
      linear regression analysis, the surgical approach was independently associated
      with postoperative cosmetic satisfaction (P<0.001). CONCLUSION: Our study found
      that cosmetic satisfaction after LESS was highest, followed by CLS, then OS.
      Therefore, physicians should more assertively discuss and consider LESS for
      gynecologic diseases.

PMID- 25978859
TI  - Effect of feeding system and breed on growth performance, and carcass and meat
      quality traits in two continental beef breeds.
AB  - A total of 100 young bulls were allotted a 2 * 2 factorial arrangement of
      treatments to determine the effect of the feeding system (concentrate and wheat
      straw: T; total mixed ration comprised of the same concentrate, maize silage and
      wheat straw: TMR) and breed (Limousine: LI; Retinta: RE) on growth performance,
      carcass characteristics and meat quality. The diets were administrated ad libitum
      for 193 days. The average daily weight gain was similar (P > 0.05) for both
      diets, while the LI bulls grew significantly (P < 0.05) more than RE. T bulls
      showed higher L*, a* and rib bone percentage. TMR bulls showed higher carcass
      yield, conformation and fatness, and greater changes in ultrasound measurements,
      except Delta UGMD and rib fat percentage. Instrumental meat quality, except shear
      force at 1 and 21 days of ageing, was not affected (P > 0.05) by the diets. Breed
      significantly affected most of the analyzed characteristics.

PMID- 25978860
TI  - When it is better to regress: dynamics of vascular pruning.
AB  - Blood vascular networks in vertebrates are essential to tissue survival.
      Establishment of a fully functional vasculature is complex and requires a number
      of steps including vasculogenesis and angiogenesis that are followed by
      differentiation into specialized vascular tissues (i.e., arteries, veins, and
      lymphatics) and organ-specific differentiation. However, an equally essential
      step in this process is the pruning of excessive blood vessels. Recent studies
      have shown that pruning is critical for the effective perfusion of blood into
      tissues. Despite its significance, vessel pruning is the least understood process
      in vascular differentiation and development. Two recently published PLOS Biology
      papers provide important new information about cellular dynamics of vascular
      regression. 

PMID- 25978861
TI  - Enantioselective HPLC determination of oxiracetam enantiomers and application to
      a pharmacokinetic study in beagle dogs.
AB  - An enantioselective high-performance liquid chromatography method was developed
      and validated for the determination of oxiracetam enantiomers, a cognition and
      memory enhancer, in beagle dog plasma. The plasma samples were prepared by
      methanol extraction from 200MUL plasma, and then the baseline resolution was
      achieved on a Chiralpak ID column (250mm*4.6mm, 5MUm) with mobile phase of hexane
      ethanol-trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0mL/min. The
      column elute was monitored using ultraviolet detection at 214nm. The method was
      linear over concentration range 0.50-100MUg/mL for both enantiomers. The relative
      standard deviation values for intra- and inter-day precision were 0.78-13.61 and
      0.74-8.92% for (R)- and (S)-oxiracetam, respectively. The relative error values
      of accuracy ranged from -4.74 to 10.48% for (R)-oxiracetam and from -0.19 to
      11.48% for (S)-oxiracetam. The method was successfully applied to a
      pharmacokinetic study of individual enantiomer and racemic oxiracetam in beagle
      dogs after oral administration. The disposition of the two enantiomers was not
      stereoselective and chiral inversion was not observed in beagle dogs. The
      pharmacokinetic profiles of (S)-oxiracetam were similar with racemic oxiracetam
      in beagle dogs. 

PMID- 25978862
TI  - Predictors for reimbursement of oncology drugs in Belgium between 2002 and 2013.
AB  - BACKGROUND: Price setting and reimbursement decisions regarding drugs are
      competence of individual member states in Europe. These decisions involve
      important trade-offs between social, ethical, clinical and economic criteria. The
      aim of this study was to investigate the relative importance of criteria for
      reimbursement of oncology drugs in Belgium. METHODS: Reimbursement dossiers on
      oncology drugs for which reimbursement was applied between 2002 and 2013 were
      consulted. Multivariate logistic regression was performed. RESULTS: Results
      showed that clinical evidence and presence of alternative treatments have a
      significant impact on the reimbursement decisions. CONCLUSIONS: Evidence-based
      medicine still plays a role in Belgian reimbursement decision-making. In order to
      allow transition towards value-based medicine and avoid spending money on
      products with limited incremental benefit, therapeutic need at patient level need
      to be taken into account.

PMID- 25978863
TI  - The continued conundrum of Hodgkin lymphoma etiology.

PMID- 25978864
TI  - How to enhance the stability of locking plate fixation of proximal humerus
      fractures? An overview of current biomechanical and clinical data.
AB  - BACKGROUND: The complication rate after locking plate fixation of proximal
      humerus fractures is high. In addition to low bone mineral density, a lack of
      medial support has been identified as one of the most important factors
      accounting for mechanical instability. As a result of the high failure rate,
      different strategies have been developed to enhance the mechanical stability of
      locking plate fixation of proximal humerus fractures. The aim of the present
      article is to give an overview of the current biomechanical and clinical studies
      that focus on how to increase the stability of locking plate fixation of proximal
      humerus fractures. METHODS: A comprehensive search of the Medline databases using
      specific search terms with regard to the stability of locking plate fixation of
      proximal humerus fractures was performed. After screening of the articles for
      eligibility, they were subdivided according to clinical and biomechanical
      aspects. RESULTS: Medial support screws, filling of bone voids and screw-tip
      augmentation with bone cement as well as the application of bone grafts are
      currently the most frequently assessed and performed methods. Although the
      evidence is weak, all of the mentioned strategies appear to have a positive
      effect on achieving and maintaining a stable reduction even of complex fractures.
      CONCLUSION: Further clinical studies with a higher number of patients and a
      higher level of evidence are required to develop a standardised treatment
      algorithm with regard to cement augmentation and bone grafting. Although these
      measures are likely to have a stabilising effect on locking plate fixation, its
      general use cannot be fully recommended yet.

PMID- 25978865
TI  - Congenital and Acquired Conditions of the Mesial Temporal Lobe: A Pictorial
      Essay.
AB  - PURPOSE: Our goal is to pictorially review a wide spectrum of congenital and
      acquired conditions affecting the medial aspect of the temporal lobe. CONCLUSION:
      After completing this article, the reader will have knowledge of the imaging
      appearance of diverse developmental, malformative, and acquired lesions of the
      mesial temporal lobe, which will be useful when evaluating pathology in this
      location.

PMID- 25978866
TI  - Use of Cardiac Magnetic Resonance Imaging Based Measurements of Inferior Vena
      Cava Cross-Sectional Area in the Diagnosis of Pericardial Constriction.
AB  - PURPOSE: To evaluate the value of cardiac magnetic resonance imaging (MRI)-based
      measurements of inferior vena cava (IVC) cross-sectional area in the diagnosis of
      pericardial constriction. METHODS: Patients who had undergone cardiac MRI for
      evaluation of clinically suspected pericardial constriction were identified
      retrospectively. The diagnosis of pericardial constriction was established by
      clinical history, echocardiography, cardiac catheterization, intraoperative
      findings, and/or histopathology. Cross-sectional areas of the suprahepatic IVC
      and descending aorta were measured on a single axial steady-state free-precession
      (SSFP) image at the level of the esophageal hiatus in end-systole. Logistic
      regression and receiver-operating curve (ROC) analyses were performed. RESULTS:
      Thirty-six patients were included; 50% (n = 18) had pericardial constriction.
      Mean age was 53.9 +/- 15.3 years, and 72% (n = 26) were male. IVC area, ratio of
      IVC to aortic area, pericardial thickness, and presence of respirophasic septal
      shift were all significantly different between patients with constriction and
      those without (P < .001 for all). IVC to aortic area ratio had the highest odds
      ratio for the prediction of constriction (1070, 95% confidence interval [8.0
      143051], P = .005). ROC analysis illustrated that IVC to aortic area ratio
      discriminated between those with and without constriction with an area under the
      curve of 0.96 (95% confidence interval [0.91-1.00]). CONCLUSIONS: In patients
      referred for cardiac MRI assessment of suspected pericardial constriction,
      measurement of suprahepatic IVC cross-sectional area may be useful in confirming
      the diagnosis of constriction when used in combination with other imaging
      findings, including pericardial thickness and respirophasic septal shift.

PMID- 25978867
TI  - Radiological Evaluation of Abdominal Endovascular Aortic Aneurysm Repair.
AB  - Endovascular aortic aneurysm repair (EVAR) is an alternative to open surgical
      repair of aortic aneurysms offering lower perioperative mortality and morbidity.
      As experience increases, clinicians are undertaking complex repairs with hostile
      aortic anatomy using branched or fenestrated devices or extra components such as
      chimneys to ensure perfusion to visceral branch vessels whilst excluding the
      aneurysm. Defining the success of EVAR depends on both clinical and radiographic
      criteria, but ultimately depends on complete exclusion of the aneurysm from the
      circulation. Aortic stent grafts are monitored using a combination of imaging
      modalities including computed tomography angiography (CTA), ultrasonography,
      magnetic resonance imaging, plain films, and nuclear medicine studies. This
      article describes when and how to evaluate aortic stent grafts using each of
      these modalities along with the characteristic features of several of the main
      stent grafts currently used in clinical practice. The commonly encountered
      complications from EVAR are also discussed and how they can be detected using
      each imaging modality. As the radiation burden from serial follow up CTA imaging
      is now becoming a concern, different follow-up imaging strategies are proposed
      depending on the complexity of the repair and based on the relative merits and
      disadvantages of each imaging modality. 

PMID- 25978868
TI  - Cadmium burden and its renal effect in inhabitants in a cadmium-contaminated
      area.

PMID- 25978870
TI  - Non-GMO genetically edited crop plants.
AB  - Direct delivery of purified Cas9 protein with guide RNA into plant cells, as
      opposed to plasmid-mediated delivery, displays high efficiency and reduced off
      target effects. Following regeneration from edited cells, the ensuing plant is
      also likely to bypass genetically modified organism (GMO) legislation as the
      genome editing complex is degraded in the recipient cells. 

PMID- 25978871
TI  - Bioprinting scale-up tissue and organ constructs for transplantation.
AB  - Bioprinting is an emerging field that is having a revolutionary impact on the
      medical sciences. It offers great precision for the spatial placement of cells,
      proteins, genes, drugs, and biologically active particles to better guide tissue
      generation and formation. This emerging biotechnology appears to be promising for
      advancing tissue engineering toward functional tissue and organ fabrication for
      transplantation, drug testing, research investigations, and cancer or disease
      modeling, and has recently attracted growing interest worldwide among researchers
      and the general public. In this Opinion, I highlight possibilities for the
      bioprinting scale-up of functional tissue and organ constructs for
      transplantation and provide the reader with alternative approaches, their
      limitations, and promising directions for new research prospects. 

PMID- 25978869
TI  - Techniques for automated local activation time annotation and conduction velocity
      estimation in cardiac mapping.
AB  - Measurements of cardiac conduction velocity provide valuable functional and
      structural insight into the initiation and perpetuation of cardiac arrhythmias,
      in both a clinical and laboratory context. The interpretation of activation
      wavefronts and their propagation can identify mechanistic properties of a broad
      range of electrophysiological pathologies. However, the sparsity, distribution
      and uncertainty of recorded data make accurate conduction velocity calculation
      difficult. A wide range of mathematical approaches have been proposed for
      addressing this challenge, often targeted towards specific data modalities,
      species or recording environments. Many of these algorithms require
      identification of activation times from electrogram recordings which themselves
      may have complex morphology or low signal-to-noise ratio. This paper surveys
      algorithms designed for identifying local activation times and computing
      conduction direction and speed. Their suitability for use in different recording
      contexts and applications is assessed. 

PMID- 25978872
TI  - Prospective study of surveillance testing for metastasis in 100 high-risk uveal
      melanoma patients.
AB  - Despite advances in the local treatment of UM, half of patients develop
      metastases typically to the liver with poor survival. Microscopic complete
      surgical resection (R0) of liver metastases improves survival in high selected
      patients. Early identification of high-risk patients might allow detection of
      asymptomatic metastases, and increase R0 liver surgery rate. From October 2006 to
      December 2009, we conducted a prospective study to detect early minimal lesions
      with 6-monthly liver function tests (LFTs) and liver MRI in 100 high-risk
      patients. High risk was defined by primary tumor clinical or genomic criteria:
      thickness>8mm or diameter>15 mm, or extra-scleral extension, or monosomy 3 by
      FISH or aCGH. With a median follow-up of 49 months, the 5-year metastasis-free
      survival and overall survival were 47 and 33%, respectively. Of the 60 patients
      who became metastatic, 50 (83%) had exclusive liver metastasis. LFTs screening
      had no sufficient accurary, but biannual MRI showed high predictive value to
      detect metastasis and select patients eligible for curative surgery: 25/50
      underwent laparotomy and among them, 8/25 (32%) had a R0 surgery. Median survival
      after metastasis was 14 months, mean survival reached 40 months in the R0
      resected population. Six-monthly liver MRI screening is recommended in patients
      with large tumors or genomic high risk in order to detect early patient
      candidates to complete resection of liver metastases.

PMID- 25978874
TI  - Store-operated Ca2+-entry and adenylyl cyclase.
AB  - One of the longest-standing effects of SOCE is in its selective regulation of
      Ca(2+)-sensitive adenylyl cyclase (AC) activity in non-excitable cells.
      Remarkably it was this source of Ca(2+) (SOCE) rather than the apparent magnitude
      of the Ca(2+)-rise that conferred AC responsiveness. The molecular basis for this
      dependence is now resolved in the case of adenylyl cyclase 8 (AC8). Sensors for
      Ca(2+) and cAMP targeted to ACs have been particularly useful in dissecting the
      influences upon and composition of what turn out to be signalling microdomains
      centred on ACs. A number of physiological processes depend on the regulation by
      SOCE of ACs, but the issue is under-studied. Here I will expand on these topics
      and point to some immediate unresolved questions. 

PMID- 25978876
TI  - Communication: Water on hexagonal boron nitride from diffusion Monte Carlo.
AB  - Despite a recent flurry of experimental and simulation studies, an accurate
      estimate of the interaction strength of water molecules with hexagonal boron
      nitride is lacking. Here, we report quantum Monte Carlo results for the
      adsorption of a water monomer on a periodic hexagonal boron nitride sheet, which
      yield a water monomer interaction energy of -84 +/- 5 meV. We use the results to
      evaluate the performance of several widely used density functional theory (DFT)
      exchange correlation functionals and find that they all deviate substantially.
      Differences in interaction energies between different adsorption sites are
      however better reproduced by DFT. 

PMID- 25978873
TI  - Butyrylcholinesterase K variant and Alzheimer's disease risk: a meta-analysis.
AB  - BACKGROUND: Although many studies have estimated the association between the
      butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the
      results are still controversial. We thus conducted this meta-analysis.
      MATERIAL/METHODS: We searched NCBI, Medline, Web of Science, and Embase databases
      to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were used to assess the strength of the association. RESULTS: We found a
      significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03
      1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant
      association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02
      1.72; P=0.04). However, no significant association between BCHE K variant and AD
      risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified
      by the age of AD onset, we found that late-onset AD (LOAD) was significantly
      associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No
      significant association between BCHE K variant and early-onset AD (EOAD) risk was
      observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE epsilon4 and
      non-BCHE K carriers, no significant association between BCHE K variant and AD
      risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE epsilon4
      carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI
      1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001).
      CONCLUSIONS: The results of this meta-analysis indicate that BCHE K variant might
      be associated with AD risk.

PMID- 25978875
TI  - In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS),
      predicts better in vivo dissolution of a weak base drug, dasatinib.
AB  - USP apparatus I and II are gold standard methodologies for determining the in
      vitro dissolution profiles of test drugs. However, it is difficult to use in
      vitro dissolution results to predict in vivo dissolution, particularly the pH
      dependent solubility of weak acid and base drugs, because the USP apparatus
      contains one vessel with a fixed pH for the test drug, limiting insight into in
      vivo drug dissolution of weak acid and weak base drugs. This discrepancy
      underscores the need to develop new in vitro dissolution methodology that better
      predicts in vivo response to assure the therapeutic efficacy and safety of oral
      drug products. Thus, the development of the in vivo predictive dissolution (IPD)
      methodology is necessitated. The major goals of in vitro dissolution are to
      ensure the performance of oral drug products and the support of drug formulation
      design, including bioequivalence (BE). Orally administered anticancer drugs, such
      as dasatinib and erlotinib (tyrosine kinase inhibitors), are used to treat
      various types of cancer. These drugs are weak bases that exhibit pH-dependent and
      high solubility in the acidic stomach and low solubility in the small intestine
      (>pH 6.0). Therefore, these drugs supersaturate and/or precipitate when they move
      from the stomach to the small intestine. Also of importance, gastric acidity for
      cancer patients may be altered with aging (reduction of gastric fluid secretion)
      and/or co-administration of acid-reducing agents. These may result in changes to
      the dissolution profiles of weak base and the reduction of drug absorption and
      efficacy. In vitro dissolution methodologies that assess the impact of these
      physiological changes in the GI condition are expected to better predict in vivo
      dissolution of oral medications for patients and, hence, better assess efficacy,
      toxicity and safety concerns. The objective of this present study is to determine
      the initial conditions for a mini-Gastrointestinal Simulator (mGIS) to assess in
      vivo dissolution of BCS class IIb drugs, dasatinib as a model drug, including the
      different gastric condition. The maximum dissolution of dasatinib with USP
      dissolution apparatus II was less than 1% in pH 6.5 SIF, while the one with mGIS
      (pH 1.2 SGF/pH 6.5 SIF) reached almost 100%. The supersaturation and
      precipitation of dasatinib were observed in the in vitro dissolution studies with
      mGIS but not with USP apparatus II. Additionally, dasatinib dissolution with mGIS
      was reduced to less than 10% when the gastric pH was elevated, suggesting the co
      administration of acid reducing agents will decrease the oral bioavailability of
      dasatinib. Accurate prediction of in vivo drug dissolution would be beneficial
      for assuring product safety and efficacy for patients. To this end, we have
      created a new in vitro dissolution system, mGIS, to predict the in vivo
      dissolution phenomena of a weak base drug, dasatinib. The experimental results
      when combined with in silico simulation suggest that the mGIS predicted the in
      vivo dissolution well due to the elevation of gastric pH. Thus, mGIS might be
      suitable to predict in vivo dissolution of weak basic drugs. This mGIS
      methodology is expected to significantly advance the prediction of in vivo drug
      dissolution. It is also expected to assist in optimizing product development and
      drug formulation design in support of Quality by Design (QbD) initiatives. 

PMID- 25978877
TI  - On a theory of stability for nonlinear stochastic chemical reaction networks.
AB  - We present elements of a stability theory for small, stochastic, nonlinear
      chemical reaction networks. Steady state probability distributions are computed
      with zero-information (ZI) closure, a closure algorithm that solves chemical
      master equations of small arbitrary nonlinear reactions. Stochastic models can be
      linearized around the steady state with ZI-closure, and the eigenvalues of the
      Jacobian matrix can be readily computed. Eigenvalues govern the relaxation of
      fluctuation autocorrelation functions at steady state. Autocorrelation functions
      reveal the time scales of phenomena underlying the dynamics of nonlinear reaction
      networks. In accord with the fluctuation-dissipation theorem, these functions are
      found to be congruent to response functions to small perturbations. Significant
      differences are observed in the stability of nonlinear reacting systems between
      deterministic and stochastic modeling formalisms. 

PMID- 25978878
TI  - Dynamically consistent method for mixed quantum-classical simulations: A
      semiclassical approach.
AB  - We introduce a new semiclassical (SC) framework, the Mixed Quantum-Classical
      Initial Value Representation (MQC-IVR), that can be tuned to reproduce existing
      quantum-limit and classical-limit SC approximations to quantum real-time
      correlation functions. Applying a modified Filinov transformation to a quantum
      limit SC formulation leads to the association of a Filinov parameter with each
      degree of freedom in the system; varying this parameter from zero to infinity
      controls the extent of quantization of the corresponding mode. The resulting MQC
      IVR expression provides a consistent dynamic framework for mixed quantum
      classical simulations and we demonstrate its numerical accuracy in the
      calculation of real-time correlation functions for a model 1D system and a model
      2D system over the full range of quantum- to classical-limit behaviors. 

PMID- 25978879
TI  - Stochastic lumping analysis for linear kinetics and its application to the
      fluctuation relations between hierarchical kinetic networks.
AB  - Conventional studies of biomolecular behaviors rely largely on the construction
      of kinetic schemes. Since the selection of these networks is not unique, a
      concern is raised whether and under which conditions hierarchical schemes can
      reveal the same experimentally measured fluctuating behaviors and unique
      fluctuation related physical properties. To clarify these questions, we introduce
      stochasticity into the traditional lumping analysis, generalize it from rate
      equations to chemical master equations and stochastic differential equations, and
      extract the fluctuation relations between kinetically and thermodynamically
      equivalent networks under intrinsic and extrinsic noises. The results provide a
      theoretical basis for the legitimate use of low-dimensional models in the studies
      of macromolecular fluctuations and, more generally, for exploring stochastic
      features in different levels of contracted networks in chemical and biological
      kinetic systems. 

PMID- 25978880
TI  - Ensemble density functional theory method correctly describes bond dissociation,
      excited state electron transfer, and double excitations.
AB  - State-averaged (SA) variants of the spin-restricted ensemble-referenced Kohn-Sham
      (REKS) method, SA-REKS and state-interaction (SI)-SA-REKS, implement ensemble
      density functional theory for variationally obtaining excitation energies of
      molecular systems. In this work, the currently existing version of the SA-REKS
      method, which included only one excited state into the ensemble averaging, is
      extended by adding more excited states to the averaged energy functional. A
      general strategy for extension of the REKS-type methods to larger ensembles of
      ground and excited states is outlined and implemented in extended versions of the
      SA-REKS and SI-SA-REKS methods. The newly developed methods are tested in the
      calculation of several excited states of ground-state multi-reference systems,
      such as dissociating hydrogen molecule, and excited states of donor-acceptor
      molecular systems. For hydrogen molecule, the new method correctly reproduces the
      distance dependence of the lowest excited state energies and describes an avoided
      crossing between the doubly excited and singly excited states. For bithiophene
      perylenediimide stacked complex, the SI-SA-REKS method correctly describes
      crossing between the locally excited state and the charge transfer excited state
      and yields vertical excitation energies in good agreement with the ab initio
      wavefunction methods. 

PMID- 25978881
TI  - A very general rate expression for charge hopping in semiconducting polymers.
AB  - We propose an expression of the hopping rate between localized states in
      semiconducting disordered polymers that contain the most used rates in the
      literature as special cases. We stress that these rates cannot be obtained
      directly from electron transfer rate theories as it is not possible to define
      diabatic localized states if the localization is caused by disorder, as in most
      polymers, rather than nuclear polarization effects. After defining the separate
      classes of accepting and inducing nuclear modes in the system, we obtain a
      general expression of the hopping rate. We show that, under the appropriate
      limits, this expression reduces to (i) a single-phonon rate expression or (ii)
      the Miller-Abrahams rate or (iii) a multi-phonon expression. The description of
      these limits from a more general expression is useful to interpolate between
      them, to validate the assumptions of each limiting case, and to define the
      simplest rate expression that still captures the main features of the charge
      transport. When the rate expression is fed with a range of realistic parameters
      the deviation from the Miller-Abrahams rate is large or extremely large,
      especially for hopping toward lower energy states, due to the energy gap law. 

PMID- 25978882
TI  - Density-functional errors in ionization potential with increasing system size.
AB  - This work investigates the effects of molecular size on the accuracy of density
      functional ionization potentials for a set of 28 hydrocarbons, including series
      of alkanes, alkenes, and oligoacenes. As the system size increases,
      delocalization error introduces a systematic underestimation of the ionization
      potential, which is rationalized by considering the fractional-charge behavior of
      the electronic energies. The computation of the ionization potential with many
      density-functional approximations is not size-extensive due to excessive
      delocalization of the incipient positive charge. While inclusion of exact
      exchange reduces the observed errors, system-specific tuning of long-range
      corrected functionals does not generally improve accuracy. These results
      emphasize that good performance of a functional for small molecules is not
      necessarily transferable to larger systems. 

PMID- 25978883
TI  - Semi-stochastic full configuration interaction quantum Monte Carlo: Developments
      and application.
AB  - We expand upon the recent semi-stochastic adaptation to full configuration
      interaction quantum Monte Carlo (FCIQMC). We present an alternate method for
      generating the deterministic space without a priori knowledge of the wave
      function and present stochastic efficiencies for a variety of both molecular and
      lattice systems. The algorithmic details of an efficient semi-stochastic
      implementation are presented, with particular consideration given to the effect
      that the adaptation has on parallel performance in FCIQMC. We further demonstrate
      the benefit for calculation of reduced density matrices in FCIQMC through replica
      sampling, where the semi-stochastic adaptation seems to have even larger
      efficiency gains. We then combine these ideas to produce explicitly correlated
      corrected FCIQMC energies for the beryllium dimer, for which stochastic errors on
      the order of wavenumber accuracy are achievable. 

PMID- 25978885
TI  - Structure and spectroscopic properties of neutral and cationic tetratomic
      [C,H,N,Zn] isomers: A theoretical study.
AB  - The structure and spectroscopic parameters of the most relevant [C,H,N,Zn]
      isomers have been studied employing high-level quantum chemical methods. For each
      isomer, we provide predictions for their molecular structure, thermodynamic
      stabilities as well as vibrational and rotational spectroscopic parameters which
      could eventually help in their experimental detection. In addition, we have
      carried out a detailed study of the bonding situations by means of a topological
      analysis of the electron density in the framework of the Bader's quantum theory
      of atoms in molecules. The analysis of the relative stabilities and spectroscopic
      parameters suggests two linear isomers of the neutral [C,H,N,Zn] composition,
      namely, cyanidehydridezinc HZnCN ((1)Sigma) and hydrideisocyanidezinc HZnNC
      ((1)Sigma), as possible candidates for experimental detections. For the cationic
      [C,H,N,Zn](+) composition, the most stable isomers are the ion-molecule complexes
      arising from the direct interaction of the zinc cation with either the nitrogen
      or carbon atom of either hydrogen cyanide or hydrogen isocyanide, namely,
      HCNZn(+) ((2)Sigma) and HCNZn(+) ((2)Sigma). 

PMID- 25978884
TI  - A unified heteronuclear decoupling strategy for magic-angle-spinning solid-state
      NMR spectroscopy.
AB  - A unified strategy of two-pulse based heteronuclear decoupling for solid-state
      magic-angle spinning nuclear magnetic resonance is presented. The analysis
      presented here shows that different decoupling sequences like two-pulse phase
      modulation (TPPM), X-inverse-X (XiX), and finite pulse refocused continuous wave
      (rCW(A)) are basically specific solutions of a more generalized decoupling scheme
      which incorporates the concept of time-modulation along with phase-modulation. A
      plethora of other good decoupling conditions apart from the standard, TPPM, XiX,
      and rCW(A) decoupling conditions are available from the unified decoupling
      approach. The importance of combined time- and phase-modulation in order to
      achieve the best decoupling conditions is delineated. The consequences of
      different indirect dipolar interactions arising from cross terms comprising of
      heteronuclear and homonuclear dipolar coupling terms and also those between
      heteronuclear dipolar coupling and chemical-shift anisotropy terms are presented
      in order to unfold the effects of anisotropic interactions under different
      decoupling conditions. Extensive numerical simulation results are corroborated
      with experiments on standard amino acids. 

PMID- 25978886
TI  - The effect of intersystem crossings in N((2)D) + H2 collisions.
AB  - The transitions between quartet and doublet states of the NH2 molecule are
      studied for the first time, allowing the evaluation of the N((4)S) + H2 reactive
      channel. High level ab initio calculations of the spin-orbit coupling are
      performed over the whole configurational space of the NH2 molecule and fitted to
      a proposed analytic form. Quasiclassical trajectories coupled with the surface
      hopping method are employed to calculate reaction cross section and rate
      constants. The reaction is largely affected by the initial rovibrational states
      of H2, while the formation of long-lived complexes enhances the reaction
      probability. 

PMID- 25978887
TI  - Electronic spectra and excited state dynamics of pentafluorophenol: Effects of
      low-lying pisigma(*) states.
AB  - Multiple fluorine atom substitution effect on photophysics of an aromatic
      chromophore has been investigated using phenol as the reference system. It has
      been noticed that the discrete vibronic structure of the S1<-S0 absorption system
      of phenol vapor is completely washed out for pentafluorophenol (PFP), and the
      latter also shows very large Stokes shift in the fluorescence spectrum. For
      excitations beyond S1 origin, the emission yield of PFP is reduced sharply with
      increase in excess vibronic energy. However, in a collisional environment like
      liquid hydrocarbon, the underlying dynamical process that drives the non
      radiative decay is hindered drastically. Electronic structure theory predicts a
      number of low-lying dark electronic states of pisigma(*) character in the
      vicinity of the lowest valence pipi(*) state of this molecule. Tentatively, we
      have attributed the excitation energy dependent non-radiative decay of the
      molecule observed only in the gas phase to an interplay between the lowest
      pipi(*) and a nearby dissociative pisigma(*) state. Measurements in different
      liquids reveal that some of the dark excited states light up with appreciable
      intensity only in protic liquids like methanol and water due to hydrogen bonding
      between solute and solvents. Electronic structure theory methods indeed predict
      that for PFP-(H2O)n clusters (n = 1-11), intensities of a number of pisigma(*)
      states are enhanced with increase in cluster size. In contrast with emitting
      behavior of the molecule in the gas phase and solutions of nonpolar and polar
      aprotic liquids, the fluorescence is completely switched off in polar protic
      liquids. This behavior is a chemically significant manifestation of perfluoro
      effect, because a very opposite effect occurs in the case of unsubstituted phenol
      for which fluorescence yield undergoes a very large enhancement in protic
      liquids. Several dynamical mechanisms have been suggested to interpret the
      observed photophysical behavior. 

PMID- 25978888
TI  - Catching the role of anisotropic electronic distribution and charge transfer in
      halogen bonded complexes of noble gases.
AB  - The systems studied in this work are gas-phase weakly bound adducts of the noble
      gas (Ng) atoms with CCl4 and CF4. Their investigation was motivated by the
      widespread current interest for the intermolecular halogen bonding (XB), a
      structural motif recognized to play a role in fields ranging from elementary
      processes to biochemistry. The simulation of the static and dynamic behaviors of
      complex systems featuring XB requires the formulation of reliable and accurate
      model potentials, whose development relies on the detailed characterization of
      strength and nature of the interactions occurring in simple exemplary halogenated
      systems. We thus selected the prototypical Ng-CCl4 and Ng-CF4 and performed high
      resolution molecular beam scattering experiments to measure the absolute scale of
      their intermolecular potentials, with high sensitivity. In general, we expected
      to probe typical van der Waals interactions, consisting of a combination of size
      (exchange) repulsion with dispersion/induction attraction. For the He/Ne-CF4, the
      analysis of the glory quantum interference pattern, observable in the velocity
      dependence of the integral cross section, confirmed indeed this expectation. On
      the other hand, for the He/Ne/Ar-CCl4, the scattering data unravelled much deeper
      potential wells, particularly for certain configurations of the interacting
      partners. The experimental data can be properly reproduced only including a
      shifting of the repulsive wall at shorter distances, accompanied by an increased
      role of the dispersion attraction, and an additional short-range stabilization
      component. To put these findings on a firmer ground, we performed, for selected
      geometries of the interacting complexes, accurate theoretical calculations aimed
      to evaluate the intermolecular interaction and the effects of the complex
      formation on the electron charge density of the constituting moieties. It was
      thus ascertained that the adjustments of the potential suggested by the analysis
      of the experiments actually reflect two chemically meaningful contributions,
      namely, a stabilizing interaction arising from the anisotropy of the charge
      distribution around the Cl atom in CCl4 and a stereospecific electron transfer
      that occurs at the intermolecular distances mainly probed by the experiments. Our
      model calculations suggest that the largest effect is for the vertex geometry of
      CCl4 while other geometries appear to play a minor to negligible role. 

PMID- 25978889
TI  - Jet cooled cavity ringdown spectroscopy of the A(2)E(")<-X~(2)A2 (') transition
      of the NO3 radical.
AB  - The A~(2)E(")<-X~(2)A2 (') spectrum of NO3 radical from 7550 cm(-1) to 9750 cm(
      1) has been recorded and analyzed. Our spectrum differs from previously recorded
      spectra of this transition due to jet-cooling, which narrows the rotational
      contours and eliminates spectral interference from hot bands. Assignments of
      numerous vibronic features can be made based on both band contour and position
      including the previously unassigned 30 (1) band and several associated
      combination bands. We have analyzed our spectrum first with an independent
      anharmonic oscillator model and then by a quadratic Jahn-Teller vibronic coupling
      model. The fit achieved with the quadratic Jahn-Teller model is excellent, but
      the potential energy surface obtained with the fitted parameters is in only
      qualitative agreement with one obtained from ab initio calculations. 

PMID- 25978890
TI  - Threshold photoelectron spectroscopy of unstable N-containing compounds:
      Resolution of DeltaK subbands in HNCO(+) and vibrational resolution in NCO(.).
AB  - The threshold photoelectron spectra (TPES) of two unstable nitrogen-containing
      species, HNCO and NCO, were recorded utilizing vacuum ultraviolet synchrotron
      radiation. Both are intermediates in combustion processes and play a role in the
      removal of nitrogen oxides from exhaust gases. The rovibronic structure of the
      first band in the TPES of HNCO(+) was analyzed within the framework of an orbital
      ionization model, and the resolved structure of the origin band was assigned to
      DeltaK subbands. An ionization energy of 11.602 +/- 0.005 eV was determined and
      the vibrational structure of the cationic ground state was analyzed by a Franck
      Condon fit. Low lying electronically excited states of HNCO(+) were also
      observed. In a second series of experiments, the NCO radical was generated by
      flash pyrolysis from chlorine isocyanate. The ionization energy to the X(+)
      (3)Sigma(-) ground state was determined to be 11.76 +/- 0.02 eV, while for the
      a(+) (1)Delta state, a value of 12.93 +/- 0.02 eV was obtained. Vibrational
      structure was observed for both states, and bands were assigned by Franck-Condon
      simulations. 

PMID- 25978891
TI  - Two-dimensional spectra of electron collisions with acrylonitrile and
      methacrylonitrile reveal nuclear dynamics.
AB  - Detailed experimental information on the motion of a nuclear packet on a complex
      (resonant) anion potential surface is obtained by measuring 2-dimensional (2D)
      electron energy loss spectra. The cross section is plotted as a function of
      incident electron energy, which determines which resonant anion state is
      populated, i.e., along which normal coordinate the wave packet is launched, and
      of the electron energy loss, which reveals into which final states each specific
      resonant state decays. The 2D spectra are presented for acrylonitrile and
      methacrylonitrile, at the incident energy range 0.095-1.0 eV, where the incoming
      electron is temporarily captured in the lowest pi(*) orbital. The 2D spectra
      reveal selectivity patterns with respect to which vibrations are excited in the
      attachment and de-excited in the detachment. Further insight is gained by
      recording 1D spectra measured along horizontal, vertical, and diagonal cuts of
      the 2D spectrum. The methyl group in methacrylonitrile increases the resonance
      width 7 times. This converts the sharp resonances of acrylonitrile into boomerang
      structures but preserves the essence of the selectivity patterns. Selectivity of
      vibrational excitation by higher-lying shape resonances up to 8 eV is also
      reported.

PMID- 25978892
TI  - First-principles investigation of the dissociation and coupling of methane on
      small copper clusters: Interplay of collision dynamics and geometric and
      electronic effects.
AB  - Small metal clusters exhibit unique size and morphology dependent catalytic
      activity. The search for alternate minimum energy pathways and catalysts to
      transform methane to more useful chemicals and carbon nanomaterials led us to
      investigate collision induced dissociation of methane on small Cu clusters. We
      report here for the first time, the free energy barriers for the collision
      induced activation, dissociation, and coupling of methane on small Cu clusters
      (Cun where n = 2-12) using ab initio molecular dynamics and metadynamics
      simulations. The collision induced activation of the stretching and bending
      vibrations of methane significantly reduces the free energy barrier for its
      dissociation. Increase in the cluster size reduces the barrier for dissociation
      of methane due to the corresponding increase in delocalisation of electron
      density within the cluster, as demonstrated using the electron localisation
      function topology analysis. This enables higher probability of favourable
      alignment of the C-H stretching vibration of methane towards regions of high
      electron density within the cluster and makes higher number of sites available
      for the chemisorption of CH3 and H upon dissociation. These characteristics
      contribute in lowering the barrier for dissociation of methane. Distortion and
      reorganisation of cluster geometry due to high temperature collision dynamics
      disturb electron delocalisation within them and increase the barrier for
      dissociation. Coupling reactions of CHx (x = 1-3) species and recombination of H
      with CHx have free energy barriers significantly lower than complete
      dehydrogenation of methane to carbon. Thus, competition favours the former
      reactions at high hydrogen saturation on the clusters. 

PMID- 25978893
TI  - Crossed-beam DC slice imaging of fluorine atom reactions with linear alkanes.
AB  - We report the reaction dynamics of F atom with selected alkanes studied by
      crossed beam scattering with DC slice ion imaging. The target alkanes are
      propane, n-butane, and n-pentane. The product alkyl radicals are probed by 157 nm
      single photon ionization following reaction at a collision energy of ~10 kcal
      mol(-1). The analyzed data are compared with the corresponding theoretical
      studies. Reduced translational energy distributions for each system show similar
      trends with little of the reaction exoergicity appearing in translation. However,
      the pentane reaction shows a somewhat smaller fraction of available energy in
      translation than the other two, suggesting greater energy channeled into pentyl
      internal degrees of freedom. The center-of-mass angular distributions all show
      backscattering as well as sharp forward scattering that decreases in relative
      intensity with the size of the molecule. Possible reasons for these trends are
      discussed. 

PMID- 25978894
TI  - Study of Ga incorporation in glassy arsenic selenides by high-resolution XPS and
      EXAFS.
AB  - Effect of Ga addition on the structure of vitreous As2Se3 is studied using high
      resolution X-ray photoelectron spectroscopy and extended X-ray absorption fine
      structure techniques. The "8-N" rule is shown to be violated for Ga atoms and,
      possibly, for certain number of As atoms. On the contrary, Se keeps its 2-fold
      coordination according to "8-N" rule in the amorphous phase throughout all the
      compositions. Crystalline inclusions appear in the amorphous structure of the
      investigated glasses at Ga concentrations greater than 3 at. %. These inclusions
      are presumably associated with Ga2Se3 crystallites and transition phases/defects
      formed at the boundaries of these crystallites and host amorphous matrix. The
      existence of Ga-As and Se-Se bonds in the samples with higher Ga content is
      supported by present studies. 

PMID- 25978895
TI  - Static dielectric properties of dense ionic fluids.
AB  - The static dielectric properties of dense ionic fluids, e.g., room temperature
      ionic liquids (RTILs) and inorganic fused salts, are investigated on different
      length scales by means of grandcanonical Monte Carlo simulations. A generally
      applicable scheme is developed which allows one to approximately decompose the
      electric susceptibility of dense ionic fluids into the orientation and the
      distortion polarization contribution. It is shown that at long range, the well
      known plasma-like perfect screening behavior occurs, which corresponds to a
      diverging distortion susceptibility, whereas at short range, orientation
      polarization dominates, which coincides with that of a dipolar fluid of attached
      cation-anion pairs. This observation suggests that the recently debated
      interpretation of RTILs as dilute electrolyte solutions might not be simply a yes
      no-question but it might depend on the considered length scale. 

PMID- 25978896
TI  - Structural and topological aspects of borophosphate glasses and their relation to
      physical properties.
AB  - We establish a topological model of alkali borophosphate and calcium
      borophosphate glasses, which describes the effect of both the network formers and
      network modifiers on physical properties. We show that the glass transition
      temperature (Tg), Vickers hardness (HV), liquid fragility (m), and isobaric heat
      capacity jump at Tg (DeltaCp) of these glasses are related to the network
      topology, which is determined by structure of the glass. Therefore, we also
      demonstrate that the temperature dependent constraint theory can quantitatively
      explain the mixed network former effect in borophosphate glasses. The origin of
      the effect of the type of network modifying oxide on Tg, HV, m, and DeltaCp of
      calcium borophosphate glasses is revealed in terms of the modifying ion sub
      network. The same topological principles quantitatively explain the significant
      differences in physical properties between the alkali and the calcium
      borophosphate glasses. This work has implications for quantifying structure
      property relations in complex glass forming systems containing several types of
      network forming and modifying oxides. 

PMID- 25978897
TI  - Glass transition dynamics and conductivity scaling in ionic deep eutectic
      solvents: The case of (acetamide + lithium nitrate/sodium thiocyanate) melts.
AB  - A detailed investigation on the molecular dynamics of ionic deep eutectic
      solvents (acetamide + lithium nitrate/sodium thiocyanate) is reported. The study
      was carried out employing dielectric relaxation spectroscopy covering seven
      decades in frequency (10(-1)-10(6) Hz) and in a wide temperature range from 373 K
      down to 173 K, accessing the dynamic observables both in liquid and glassy state.
      The dielectric response of the ionic system has been presented in the dynamic
      window of modulus formalism to understand the conductivity relaxation and its
      possible connection to the origin of localized motion. Two secondary relaxation
      processes appear below glass transition temperature. Our findings provide
      suitable interpretation on the nature of secondary Johari-Goldstein process
      describing the ion translation and orientation of dipoles in a combined approach
      using Ngai's coupling model. A nearly constant loss feature is witnessed at
      shorter times/lower temperatures. We also discuss the ac conductivity scaling
      behavior using Summerfield approach and random free energy barrier model which
      establish the time-temperature superposition principle. These experimental
      observations have fundamental importance on theoretical elucidation of the
      conductivity relaxation and glass transition phenomena in molten ionic
      conductors. 

PMID- 25978898
TI  - Observation and theory of reorientation-induced spectral diffusion in
      polarization-selective 2D IR spectroscopy.
AB  - In nearly all applications of ultrafast multidimensional infrared spectroscopy,
      the spectral degrees of freedom (e.g., transition frequency) and the orientation
      of the transition dipole are assumed to be decoupled. We present experimental
      results which confirm that frequency fluctuations can be caused by rotational
      motion and observed under appropriate conditions. A theory of the frequency
      frequency correlation function (FFCF) observable under various polarization
      conditions is introduced, and model calculations are found to reproduce the
      qualitative trends in FFCF rates. The FFCF determined with polarization-selective
      two-dimensional infrared (2D IR) spectroscopy is a direct reporter of the
      frequency-rotational coupling. For the solute methanol in a room temperature
      ionic liquid, the FFCF of the hydroxyl (O-D) stretch decays due to spectral
      diffusion with different rates depending on the polarization of the excitation
      pulses. The 2D IR vibrational echo pulse sequence consists of three excitation
      pulses that generate the vibrational echo, a fourth pulse. A faster FFCF decay is
      observed when the first two excitation pulses are polarized perpendicular to the
      third pulse and the echo, <XXY Y>, than in the standard all parallel
      configuration, <XXXX>, in which all four pulses have the same polarization. The
      2D IR experiment with polarizations <XY XY> ("polarization grating"
      configuration) gives a FFCF that decays even more slowly than in the <XXXX>
      configuration. Polarization-selective 2D IR spectra of bulk water do not exhibit
      polarization-dependent FFCF decays; spectral diffusion is effectively decoupled
      from reorientation in the water system. 

PMID- 25978899
TI  - Influence of grain size on optical properties of Sr2CeO4 nanocrystals.
AB  - The absorption, excitation, and emission spectra of the Sr2CeO4 nanocrystals
      prepared by the modified sol-gel method were investigated. The impact of the
      average grain size of Sr2CeO4 nanocrystals on their optical properties was
      investigated. It was observed that with increasing the average grain size of
      Sr2CeO4 nanocrystals, the emission decay times decreased significantly. A similar
      behavior was observed for the emission quantum efficiencies and the Huang-Rhys
      factors. The grain size dependence of optical parameters of Sr2CeO4 nanocrystals
      was found well fitted by functions of the reciprocal of the grain diameter. It
      was shown that this dependence may be rationalized assuming that the correction
      for electric local field associated with effective refractive index affecting the
      spherical nanoparticle is governed by its shell. 

PMID- 25978900
TI  - An electron energy-loss study of picene and chrysene based charge transfer salts.
AB  - The electronic excitation spectra of charge transfer compounds built from the
      hydrocarbons picene and chrysene, and the strong electron acceptors F4TCNQ
      (2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane) and TCNQ (7,7,8,8
      tetracyanoquinodimethan) have been investigated using electron energy-loss
      spectroscopy. The corresponding charge transfer compounds have been prepared by
      co-evaporation of the pristine constituents. We demonstrate that all investigated
      combinations support charge transfer, which results in new electronic excitation
      features at low energy. This might represent a way to synthesize low band gap
      organic semiconductors. 

PMID- 25978901
TI  - Dielectric constant of water as a function of separation in a slab geometry: A
      molecular dynamics study.
AB  - Water in confining geometries shows various anomalous properties related to its
      structure and dynamics compared with bulk water. Here, the dielectric constant of
      water as a function of separation in a graphite slab geometry was studied using
      molecular dynamics simulations. The dielectric constants of water were calculated
      from the orientational polarization of water molecules when an external electric
      field was applied parallel and normal to the slabs. The reduction of the
      dielectric constant of water compared with bulk water can be explained by
      investigating the structure and dynamics of water in slab geometries. We found a
      preferred orientation of water molecules in the layer closest to the graphite
      surface. The self-diffusion coefficient distribution of water molecules along the
      direction normal to the slabs was also computed. Highly mobile water molecules in
      the intermediate region were generated by the weak hydrogen bonding produced by
      the preferred orientation of water molecules in the layer. We concluded that the
      dielectric constant of water in the slab geometry is lower than that of bulk
      water because of the reduction of the polarization of water and the highly mobile
      water molecules in the intermediate region arising from the preferred orientation
      of water molecules. 

PMID- 25978902
TI  - Molecular simulations of heterogeneous ice nucleation. I. Controlling ice
      nucleation through surface hydrophilicity.
AB  - Ice formation is one of the most common and important processes on earth and
      almost always occurs at the surface of a material. A basic understanding of how
      the physicochemical properties of a material's surface affect its ability to form
      ice has remained elusive. Here, we use molecular dynamics simulations to directly
      probe heterogeneous ice nucleation at a hexagonal surface of a nanoparticle of
      varying hydrophilicity. Surprisingly, we find that structurally identical
      surfaces can both inhibit and promote ice formation and analogous to a chemical
      catalyst, it is found that an optimal interaction between the surface and the
      water exists for promoting ice nucleation. We use our microscopic understanding
      of the mechanism to design a modified surface in silico with enhanced ice
      nucleating ability. 

PMID- 25978903
TI  - Molecular simulations of heterogeneous ice nucleation. II. Peeling back the
      layers.
AB  - Coarse grained molecular dynamics simulations are presented in which the
      sensitivity of the ice nucleation rate to the hydrophilicity of a graphene
      nanoflake is investigated. We find that an optimal interaction strength for
      promoting ice nucleation exists, which coincides with that found previously for a
      face centered cubic (111) surface. We further investigate the role that the
      layering of interfacial water plays in heterogeneous ice nucleation and
      demonstrate that the extent of layering is not a good indicator of ice nucleating
      ability for all surfaces. Our results suggest that to be an efficient ice
      nucleating agent, a surface should not bind water too strongly if it is able to
      accommodate high coverages of water. 

PMID- 25978904
TI  - Superpermittivity of nanoconfined water.
AB  - Nowadays, it is well established that the physical properties of confined liquids
      strongly differ from those in bulk phase. While dynamical and structural
      properties were strongly explored, dielectric properties are poorly studied
      despite their importance in the understanding and the modelling of molecular
      mechanism in a number of nano-applications such as nanofluidics, nanofiltration,
      and nanomedicine. Among them, the dielectric permittivity is probably one of the
      most important. The lack of knowledge about it strongly limits our ability to
      model fluid-material interactions and more generally our understanding of the
      behaviour of confined fluids. Recently, the dielectric permittivity of confined
      water in silica, Metal Organic Frameworks, and graphene materials was found to be
      slightly higher than the permittivity of water in bulk phase. In this work, the
      permittivity of water and dichloromethane confined in carbon nanotubes was
      predicted by means of molecular dynamics simulations. The static dielectric
      constant was found to be 700, i.e., 10-fold higher than the bulk value. This
      superpermittivity has, for origin, the excluded volume and the presence of an
      unconfined direction leading to a pre-orientation of water molecules close to the
      pore wall and an increase in dipolar fluctuations. 

PMID- 25978905
TI  - Optical microcavities enhance the exciton coherence length and eliminate vibronic
      coupling in J-aggregates.
AB  - The properties of polaritons in J-aggregate microcavities are explored using a
      Hamiltonian which treats exciton-vibrational coupling and exciton-photon coupling
      on equal footing. When the cavity mode is resonant with the lowest-energy (0-0)
      transition in the J-aggregate, two polaritons are formed, the lowest-energy
      polariton (LP) and its higher-energy partner (P1), separated by the Rabi
      splitting. Strong coupling between the material and cavity modes leads to a
      decoupling of the exciton and vibrational degrees of freedom and an overall
      reduction of disorder within the LP. Such effects lead to an expanded material
      coherence length in the LP which leads to enhanced radiative decay rates.
      Additional spectral signatures include an amplification of the 0-0 peak
      coincident with a reduction in the 0-1 peak in the photoluminescence spectrum. It
      is also shown that the same cavity photon responsible for the LP/P1 splitting
      causes comparable splittings in the higher vibronic bands due to additional
      resonances between vibrationally excited states in the electronic ground state
      manifold and higher energy vibronic excitons. 

PMID- 25978906
TI  - Electronic, structural, and substrate effect properties of single-layer covalent
      organic frameworks.
AB  - Recently synthesized two-dimensional covalent organic frameworks (COFs) exhibit
      high surface area, large pore size, and unique structural architectures, making
      them promising materials for various energy applications. Here, a total of nine
      COFs structures, including two deposited on a hexagonal boron nitride substrate,
      are investigated using density functional theory, quasi-particle many-body theory
      within the GW approximation, and an image charge model. The structures considered
      belong to two major families (thiophene-based COF-n (T-COF-n) and tetrakis (4
      aminophenyl) porphyrin-x (TAPP-x)) differing from the presence of B-O or C=N
      linkers. While T-COF-n structures are shown to constitute planar networks, TAPP-x
      systems can display non-negligible corrugation due to the out-of-plane rotation
      of phenyl rings. We find that the electronic properties do not differ
      significantly when altering the chain molecules within each family. Many-body
      effects are shown to lead to large band-gap increase while the presence of the
      substrate yields appreciable reductions of the gaps, due to substrate
      polarization effects. 

PMID- 25978907
TI  - Kinetically induced irreversibility in electro-oxidation and reduction of Pt
      surface.
AB  - A mean field kinetic model was developed for electrochemical oxidations and
      reductions of Pt(111) on the basis of density functional theory calculations, and
      the reaction mechanisms were analyzed. The model reasonably describes asymmetric
      shapes of cyclic voltammograms and small Tafel slopes of relevant redox reactions
      observed in experiments without assuming any unphysical forms of rate equations.
      Simulations using the model indicate that the oxidation of Pt(111) proceeds via
      an electrochemical oxidation from Pt to PtOH and a disproportionation reaction
      from PtOH to PtO and Pt, while its reduction proceeds via two electrochemical
      reductions from PtO to PtOH and from PtOH to Pt. 

PMID- 25978908
TI  - Isotropic-nematic phase transition of polydisperse clay rods.
AB  - Rod-like colloidal particles are known to display an isotropic-nematic phase
      transition on increase of concentration, as predicted already by Onsager. Both
      natural clay particles and synthetic rods tend to be polydisperse, however, and
      the question arises how to allow for this in comparing experimental observations
      with theory. Experimental data for a wide range of samples (both from the
      literature and the new results) have been collated, with aspect ratios ranging
      from 14 to 35. As a characteristic, the concentration is taken where half of the
      sample volume is nematic. Experimental data agree well with predictions for
      monodisperse finite aspect ratio rods. However, compared to these predictions,
      the width of the transition (taken as the ratio of isotropic and nematic limiting
      concentrations) is noticeably broadened. Still, in most cases, the transition can
      be characterised by a linear increase of the nematic phase volume with sample
      concentration. The transition width is in broad agreement with theoretical
      predictions for infinitely thin rods. 

PMID- 25978909
TI  - Optimizing the fabrication process and interplay of device components of polymer
      solar cells using a field-based multiscale solar-cell algorithm.
AB  - Both the device composition and fabrication process are well-known to crucially
      affect the power conversion efficiency of polymer solar cells. Major advances
      have recently been achieved through the development of novel device materials and
      inkjet printing technologies, which permit to improve their durability and
      performance considerably. In this work, we demonstrate the usefulness of a
      recently developed field-based multiscale solar-cell algorithm to investigate the
      influence of the material characteristics, like, e.g., electrode surfaces,
      polymer architectures, and impurities in the active layer, as well as post
      production treatments, like, e.g., electric field alignment, on the photovoltaic
      performance of block-copolymer solar-cell devices. Our study reveals that a short
      exposition time of the polymer bulk heterojunction to the action of an external
      electric field can lead to a low photovoltaic performance due to an incomplete
      alignment process, leading to undulated or disrupted nanophases. With increasing
      exposition time, the nanophases align in direction to the electric field lines,
      resulting in an increase of the number of continuous percolation paths and,
      ultimately, in a reduction of the number of exciton and charge-carrier losses.
      Moreover, we conclude by modifying the interaction strengths between the
      electrode surfaces and active layer components that a too low or too high
      affinity of an electrode surface to one of the components can lead to defective
      contacts, causing a deterioration of the device performance. Finally, we infer
      from the study of block-copolymer nanoparticle systems that particle impurities
      can significantly affect the nanostructure of the polymer matrix and reduce the
      photovoltaic performance of the active layer. For a critical volume fraction and
      size of the nanoparticles, we observe a complete phase transformation of the
      polymer nanomorphology, leading to a drop of the internal quantum efficiency. For
      other particle-numbers and -sizes, we observe only a local perturbation of the
      nanostructure, diminishing the number of continuous percolation paths to the
      electrodes and, therefore, reducing the device performance. From these
      investigations, we conclude that our multiscale solar-cell algorithm is an
      effective approach to investigate the impact of device materials and post
      production treatments on the photovoltaic performance of polymer solar cells. 

PMID- 25978910
TI  - The dispersion state of magnetic nanorods in homopolymers and block copolymers.
AB  - We investigated the dispersion state of pyridine-modified magnetic nanorods in
      poly(2 vinylpyridine) (P2VP) homopolymers and poly(styrene-b-2 vinylpyridine) (PS
      P2VP) diblock copolymers. In the P2VP/nanorod mixtures, the dispersion of
      nanorods was enhanced in systems in which the molecular weight of P2VP was
      increased because the long P2VP chains provided steric hindrance and thus
      screened the attractive interparticle interactions, inhibiting the rod
      aggregation. When nanorods were mixed with PS-P2VP, the phase stability of the
      mixtures varied considerably according to changes in the lamellar period of PS
      P2VP (D). When D was large, nanorods were sequestered into the P2VP domains
      through enthalpically driven self-assembly, and the nanorods became spatially
      organized. By contrast, when D was small, the introduction of nanorods caused
      substantial distortion of chain conformations. This entropically unfavorable
      condition can be offset by excluding nanorods from the ordered phases, causing
      particle aggregation. At a high particle loading, the attractive interparticle
      interactions outweighed the particle-polymer interaction and entropic
      contribution of polymers. Consequently, nanorods underwent extensive aggregation.

PMID- 25978911
TI  - New strategy to create ultra-thin surface layer of grafted amphiphilic
      macromolecules.
AB  - It was found first that macromolecules made of amphiphilic monomer units could
      form spontaneously an ultra-thin layer on the surface which the macromolecules
      are grafted to. The width of such layer is about double size of monomer unit
      consisting of hydrophilic A (repulsive) and hydrophobic (attractive) B beads. The
      hydrophilic A beads are connected in a polymer chain while hydrophobic B beads
      are attached to A beads of the backbone as side groups. Three characteristic
      regimes are distinguished. At low grafting density, the macromolecules form ultra
      thin micelles of the shape changing with decrease of distance d between grafting
      points as following: circular micelles-prolonged micelles-inverse micelles
      homogeneous bilayer. Those micelles have approximately constant height and
      specific top-down A-BB-A structure. At higher grafting density, the micelles
      start to appear above the single bilayer of amphiphilic macromolecules. The
      thickness of grafted layer in these cases is different in different regions of
      grafting surface. Only at rather high density of grafting, the height of
      macromolecular layer becomes uniform over the whole grafting surface. The study
      was performed by computer modeling experiments and confirmed in framework of
      analytical theory. 

PMID- 25978912
TI  - Ion mixing, hydration, and transport in aqueous ionic systems.
AB  - The enhancement effect on the ion mobility of fluoride (and that of chloride) in
      a polycationic system, as the chloride content increases, is shown to also exist
      in other more simple ionic systems with cations such as the cesium ion and an
      organic ammonium ion. As the chloride content increases, in addition to the
      finding that there is more unbound water associated with the cation, we also
      observe that the average lifetime of a hydrogen bond decreases. This change to
      the hydrogen bonds is correlated to significant changes to both the structural
      and dynamical properties of water. The more disordered water structure and faster
      water dynamics are hypothesized to be also responsible for the enhanced ion
      mobilities. Furthermore, when either the chloride content or hydration level is
      changed, the self-diffusion constant of each co-ion changes by almost the same
      factor, implying the existence of a single universal transport mechanism that
      determines ion mobilities. 

PMID- 25978913
TI  - Dynamic memory of a single voltage-gated potassium ion channel: A stochastic
      nonequilibrium thermodynamic analysis.
AB  - In this work, we have studied the stochastic response of a single voltage-gated
      potassium ion channel to a periodic external voltage that keeps the system out-of
      equilibrium. The system exhibits memory, resulting from time-dependent driving,
      that is reflected in terms of dynamic hysteresis in the current-voltage
      characteristics. The hysteresis loop area has a maximum at some intermediate
      voltage frequency and disappears in the limits of low and high frequencies.
      However, the (average) dissipation at long-time limit increases and finally goes
      to saturation with rising frequency. This raises the question: how diminishing
      hysteresis can be associated with growing dissipation? To answer this, we have
      studied the nonequilibrium thermodynamics of the system and analyzed different
      thermodynamic functions which also exhibit hysteresis. Interestingly, by applying
      a temporal symmetry analysis in the high-frequency limit, we have analytically
      shown that hysteresis in some of the periodic responses of the system does not
      vanish. On the contrary, the rates of free energy and internal energy change of
      the system as well as the rate of dissipative work done on the system show
      growing hysteresis with frequency. Hence, although the current-voltage hysteresis
      disappears in the high-frequency limit, the memory of the ion channel is
      manifested through its specific nonequilibrium thermodynamic responses. 

PMID- 25978914
TI  - Designing pH induced fold switch in proteins.
AB  - This work investigates the computational design of a pH induced protein fold
      switch based on a self-consistent mean-field approach by identifying the ensemble
      averaged characteristics of sequences that encode a fold switch. The primary
      challenge to balance the alternative sets of interactions present in both target
      structures is overcome by simultaneously optimizing two foldability criteria
      corresponding to two target structures. The change in pH is modeled by altering
      the residual charge on the amino acids. The energy landscape of the fold switch
      protein is found to be double funneled. The fold switch sequences stabilize the
      interactions of the sites with similar relative surface accessibility in both
      target structures. Fold switch sequences have low sequence complexity and hence
      lower sequence entropy. The pH induced fold switch is mediated by attractive
      electrostatic interactions rather than hydrophobic-hydrophobic contacts. This
      study may provide valuable insights to the design of fold switch proteins. 

PMID- 25978915
TI  - Erratum: "Self-consistent embedding of density-matrix renormalization group
      wavefunctions in a density functional environment" [J. Chem. Phys. 142, 044111
      (2015)].

PMID- 25978916
TI  - Publisher's Note: "Reactive scattering calculations for (87)Rb+(87)RbHe
      >Rb2((3)Sigmau (+),v)+He from ultralow to intermediate energies" [J. Chem. Phys.
      142, 164304 (2015)].

PMID- 25978917
TI  - [Sirolimus associated pneumonitis in a hematopoietic stem cell transplant
      patient].
AB  - BACKGROUND AND OBJECTIVE: Sirolimus (SR) is a lipophilic macrocytic lactone with
      immunosuppressive properties (mTOR inhibitor) commonly used in solid organ
      transplantation and recently introduced in the prophylaxis and treatment of graft
      versus-host disease. Its numerous side effects include: hyperlipidemia,
      arthralgias, noncardiac peripheral edema, thrombotic microangiopathy and
      interstitial pneumonitis. SR-associated pneumonitis is a rare but potentially
      serious complication due to its increasing utilization in transplant patients.
      PATIENT AND METHOD: We report the case of a patient undergoing hematopoietic stem
      cell transplantation with severe respiratory distress and SR therapy. RESULTS:
      Microbiological tests were all negative and other complications related to
      transplantation were discarded. The chest computed tomography of high-resolution
      showed pneumonitis. The SR therapy was interrupted and treatment was started with
      steroids with resolution of symptoms. CONCLUSIONS: SR associated pneumonitis is a
      potentially fatal side effect. In patients treated with SR and respiratory
      failure, we must suspect this complication because early recognition along with
      drug discontinuation and steroid treatment is essential to reverse this
      complication.

PMID- 25978918
TI  - [Serotoninergic syndrome due to interaction between linezolid and 5
      hydroxytryptophan].

PMID- 25978919
TI  - [Accuracy in the medication history and reconciliation errors in the emergency
      department].
AB  - BACKGROUND AND OBJECTIVE: To assess the accuracy of pharmaceutical anamnesis
      obtained at the Emergency Department (ED) of a tertiary referral hospital and to
      determine the prevalence of medication reconciliation errors (RE). MATERIAL AND
      METHOD: This was a single-center, prospective, interventional study. The home
      medication list obtained by a pharmacist was compared with the one recorded by a
      doctor to identify inaccuracies. Subsequently, the home medication list was
      compared with the active prescription at the ED. All unexplained discrepancies
      were checked with the doctor in charge to evaluate if a RE has occurred. An
      univariate analysis was performed to identify factors associated with RE.
      RESULTS: The pharmacist identified a higher number of drugs than doctors (6.89
      versus 5.70; P<0.05). Only 39% of the drugs obtained by doctors were properly
      written down in the patient's record. The main cause of discrepancy was omission
      of information regarding the name of the drug (39%) or its dosage (33%). One
      hundred and fifty-seven RE were identified and they affected 85 patients (43%),
      mainly related to information omission (62%). Age and polymedication were
      identified as main risk factors of RE. The presence of a caregiver or relative in
      the ED was judged to be a protective factor. No relationship was found between
      inaccuracies in the registries and RE. CONCLUSIONS: The process of obtaining a
      proper pharmaceutical anamnesis still needs improvement. The pharmacist may play
      a role in the process of obtaining a good quality anamnesis and increase patient
      safety by detecting RE. Better information systems are needed to avoid this type
      of incidents.

PMID- 25978920
TI  - [Prognostic implications of extra-hepatic clinical manifestations, autoimmunity
      and microscopic nail capillaroscopy in patients with primary biliary cirrhosis].
AB  - BACKGROUND AND OBJECTIVES: Primary biliary cirrhosis (PBC) is associated to any
      systemic autoimmune disease (SAD), in particular systemic sclerosis (SSc). To
      investigate the prevalence of SAD in a cohort of patients with PBC, specifically
      the prevalence of SSc and its clinical subtypes, and determining the clinical and
      biological profile of patients with associated PBC and SSc. METHODS:
      Observational study of 62 patients with PBC following a protocol that included an
      anamnesis and physical examination to detect the presence of SAD as well as a
      nailfold capillaroscopy and an immunological study with specific SSc
      autoantibodies. A comparative analysis was conducted between patients with
      isolated PBC and patients with PBC and an associated SAD. RESULTS: SAD was
      associated to PBC in 22 patients (35,4%), and SSc was the most frequent illness,
      identified in 13 cases (21%). Five patients (8%) without previous diagnosis of
      SAD fulfilled pre-scleroderma criteria, according to LeRoy and Medsger criteria.
      The presence of anticentromere antibodies (54,5% vs. 5%, P<.001) was the unique
      immunological determination identified more frequently in patients with PBC-SAD.
      The SSc suggestive capillary pattern was visualized in 11 patients (20,4%),
      mainly the slow pattern. No factors associated with greater morbi-mortality were
      identified in the PBC-SAD group. CONCLUSIONS: It does exist a subgroup of
      patients with PBC and clinical-biological features suggestive of an SAD, which
      advise a protocolized study to detect early the association to an SAD.

PMID- 25978921
TI  - [Expulsive medical treatment of ureteral stone with adrenergic alfa-blockers].

PMID- 25978922
TI  - [Serum tumour markers in asymptomatic patients].

PMID- 25978923
TI  - [Varicella infection in pregnancy].

PMID- 25978924
TI  - [Biosimilars: current reality, promising future?].

PMID- 25978925
TI  - [Incidence of hip fracture in Spain (1997-2010)].
AB  - BACKGROUND AND OBJECTIVE: To analyse differences in the incidence of hip fracture
      in people older than 65 years in the 17 autonomous communities (AA. CC.)
      (regions) of the Spanish state in the 1997-2010 period. MATERIAL AND METHODS:
      Ecological, observational and retrospective study that includes people>=65 year
      old who have suffered a hip fracture in Spain over 14 years. These records are
      taken from the minimum basic data set of patients treated in all hospitals of
      Spain. RESULTS: The analysis include 534,043 hip fractures in>=65 year olds
      (414,518 women and 119,525 men). A percentage of 85.4 of hip fractures occurred
      in people>=75 years (86.7% women; 80.7% men). The adjusted hip fracture
      rate/100,000/year was 722.6 in women and 284.8 in men. AA. CC. with women above
      the average of the country were 7, including Catalonia, Comunidad Valenciana and
      Castilla-La Mancha. Six AA. CC. had patients below the average, including Canary
      Islands and Galicia. In AA. CC. with highest and lowest adjusted hip fracture
      rate/100,000/year, the difference was 44% lower in women (Canary vs. Castilla-La
      Mancha) and 50% lower in men (Galicia vs. Catalonia). CONCLUSIONS: The analysis
      of the incidence of hip fracture in Spain in people>=65 year old shows a
      significant variability between AA. CC. Except in Canary Islands, this
      variability is difficult to explain only by factors such as population age, sun
      exposure or north-south gradient. Additional studies are needed to analyse the
      causes of these important differences between Spanish AA. CC.

PMID- 25978926
TI  - Exploring the relationship between childhood adversity and oral health: An
      anecdotal approach and integrative view.
AB  - During the past two decades, increasing recognition has been given to a
      relationship between oral health and systemic diseases. Associated systemic
      conditions include cardiovascular disease, diabetes, low birth weight and preterm
      births, respiratory diseases, rheumatoid arthritis, obesity, osteoporosis, and,
      in particular among oral conditions, periodontal disease. Low-grade inflammation
      is a common denominator linking these disorders. Applying an anecdotal approach
      and an integrative view, the medical and dental histories of two women document
      increasing ill health subsequent to incidences of maltreatment and sexual abuse,
      including oral penetration, at an early age. Comprehensive oral rehabilitation
      was required in both cases. These cases open for medical insight with regard to
      their implicit patho-physiology, when integrated with current evidence from
      neuroscience, endocrinology, and immunology, converging in the concepts of
      allostasis and allostatic load. In cases such as those presented in this paper,
      primary care physicians (family doctors, General Practitioners) and dentists may
      be the first to identify an etiological pattern. This report underlines the
      importance of increased and enhanced multidisciplinary research cooperation among
      health professionals. Our hypothesis is that childhood adversity may affect all
      aspects of human health, including adult oral health. 

PMID- 25978928
TI  - Lateral antebrachial cutaneous nerve compression after subpectoral biceps
      tenodesis: a case report.

PMID- 25978927
TI  - The "Sea" should not be operated on in scar revision for "Island-Like" scars.
AB  - Scars developing on body surfaces not only restrict body movement, but are also
      problematic from a cosmetic standpoint. Hence, revision is conducted by removing
      the scar and re-suturing the resultant defects. In performing scar revision, care
      should be taken to prevent the re-sutured wounds from developing hypertrophy
      again. Scars often present a pattern where hard, red parts are separated by soft
      parts in between. As the hard and soft parts may be analogized as islands and
      seas respectively, we call this the "Island-Like" scar. Two strategies can be
      taken to treat scars of this type. The first is to remove the entire scar
      including both hard and soft parts; the second is to remove only the hard parts
      and leave the soft parts untouched. The authors conducted a biomechanical study
      using finite element analyses and found that as a body moves, greater stresses
      occur in the peri-wound regions with the first strategy than with the second
      strategy. A wound's likelihood to develop hypertrophy increases as the stresses
      working on it increase. Hence, it is hypothesized that the second strategy
      carries less risk of the operated wounds developing re-hypertrophy than the first
      strategy. Based on this logic, in performing scar revision for scars consisting
      of hard and soft parts, it is recommended only to remove only hard parts and not
      to operate on soft parts in between. 

PMID- 25978929
TI  - Carp thrombocyte phagocytosis requires activation factors secreted from other
      leukocytes.
AB  - Thrombocytes are nucleated blood cells in non-mammalian vertebrates, which were
      recently focused on not only as hemostatic cells but also as immune cells with
      potent phagocytic activities. We have analyzed the phagocytic activation
      mechanisms in common carp (Cyprinus carpio) thrombocytes. MACS-sorted mAb(+)
      thrombocytes showed no phagocytic activity even in the presence of several
      stimulants. However, remixing these thrombocytes with other anti-thrombocyte mAb(
      ) leukocyte populations restored their phagocytic activities, indicating that
      carp thrombocyte phagocytosis requires an appropriate exogenous stimulation.
      Culture supernatant from anti-thrombocyte mAb(-) leukocytes harvested after PMA
      or LPS stimulation, but not culture supernatant from unstimulated leukocytes,
      could activate thrombocyte phagocytosis. This proposed mechanism of thrombocyte
      phagocytosis activation involving soluble factors produced by activated
      leukocytes suggests that thrombocyte activation is restricted to areas proximal
      to injured tissues, ensuring suppression of excessive thrombocyte activation and
      a balance between inflammation and tissue repair. 

PMID- 25978930
TI  - Tuning the interactions of PEG-coated gold nanorods with BSA and model proteins
      through insertion of amino or carboxylate groups.
AB  - Gold nanorods (GNRs) are important platforms for biosensing and drug delivery. As
      for most nanomaterials, appropriate coatings such as polyethylene glycol (PEG)
      are needed to stabilize GNRs within biological fluids. We show here that the
      interactions of GNRs with proteins can be finely modulated through surface
      modification using PEG-containing chains bearing charged headgroups.
      Interestingly, introduction of amino or carboxylate groups produces relevant and
      differential changes in GNR interactions with three representative proteins:
      lysozyme, cytochrome c, and bovine serum albumin. These effects were explored
      through the direct monitoring of plasmonic bands of the GNRs and are supported by
      independent dynamic light scattering (DLS) and circular dichroism (CD)
      determinations. Notably, GNR-protein interactions observed for these charged GNRs
      can be almost completely reversed by salt addition. These observations
      demonstrate the importance of electrostatic effects in governing GNR-protein
      interactions, and provide a basis for new sensing and delivery platforms. 

PMID- 25978931
TI  - Magnetic susceptibility of Mn(III) complexes of hydroxamate siderophores.
AB  - The hydroxamate siderophores putrebactin, desferrioxamine B, and desferrioxamine
      E bind Mn(II) and promote the air oxidation of Mn(II) to Mn(III) at pH>7.1. The
      magnetic susceptibility of the manganese complexes were determined by the Evans
      method and the stoichiometry was probed with electrospray ionization mass
      spectrometry (ESIMS). The room temperature magnetic moments (MUeff) for the
      manganese complexes of desferrioxamines B and E were 4.85 BM and 4.84 BM,
      respectively, consistent with a high spin, d(4), Mn(III) electronic
      configuration. The manganese complex of putrebactin had a magnetic moment of 4.98
      BM, consistent with incomplete oxidation of Mn(II), as confirmed by X band EPR
      spectroscopy. Mass spectra of the Mn(III) desferrioxamine B and E complexes
      showed complexes at m/z 613.26 and 653.26, respectively, consistent with 1:1
      complexation. Mass spectral peaks for manganese putrebactin at m/z 797.31 and
      1221.41 corresponds to 1:2 and 2:3 Mn:putrebactin complexation. This study
      directly confirms the Mn(III) oxidation state in hydroxamate siderophore
      complexes.

PMID- 25978932
TI  - Response to Letter to the Editor.

PMID- 25978933
TI  - Increased activity of frontal and limbic regions to emotional stimuli in children
      at-risk for anxiety disorders.
AB  - Neuroimaging studies of children with anxiety disorders are limited, and no study
      has examined children who are at increased risk for developing anxiety disorders
      based on parental anxiety. The objective of this study was to examine the
      function of frontal and limbic brain regions using functional magnetic resonance
      imaging (fMRI) in children at risk for anxiety disorders. Study participants
      included high-risk children (n=20) who had at least one parent with a primary
      diagnosis of social anxiety disorder and normal-risk control children (n=19).
      Using fMRI, we measured the blood oxygenation level dependent response while high
      risk and normal-risk children were exposed to different emotional facial stimuli.
      We found greater activation of frontal, temporal and limbic regions in high-risk
      children relative to normal-risk children during the presentation of emotional
      stimuli (angry and happy). These regions included the prefrontal cortex, anterior
      cingulate, hippocampus and insula. Our within-group analysis revealed similar
      patterns of hyperactivity in high-risk children with and without current anxiety
      symptoms. To our knowledge, this is the first study to demonstrate functional
      alterations in emotion-processing brain regions in children who are at risk for
      anxiety disorders based on parental anxiety. These findings are consistent with
      previous fMRI studies of pediatric anxiety and behaviorally inhibited children,
      and they contribute to our understanding of the neural correlates of risk for
      anxiety disorders.

PMID- 25978934
TI  - Reduced prefrontal activation during performance of the Iowa Gambling Task in
      patients with bipolar disorder.
AB  - The Iowa Gambling Task (IGT) is a complex decision-making task in which monetary
      wins and losses guide the development of strategies. The objective of this study
      was to evaluate hemodynamic responses of patients with bipolar disorder (BD)
      during performance of the IGT using near-infrared spectroscopy (NIRS).
      Participants comprised 13 patients and 15 healthy control subjects who were
      matched for age, sex, handedness, and intelligence quotient. Relative changes in
      oxygenated and deoxygenated hemoglobin (oxy-Hb and deoxy-Hb) levels in the
      frontal region were measured using a 46-channel NIRS system. All subjects were
      evaluated using NIRS during a verbal fluency task (VFT) and the IGT. During
      performance of the IGT, BD patients showed significantly decreased oxy-Hb levels
      in the bilateral orbitofrontal cortex (OFC) and left prefrontal cortex (PFC)
      compared with normal control subjects. However, during the VFT, patients with BD
      showed no significant changes in oxy-Hb levels compared with control subjects.
      Changes in oxy-Hb levels in the bilateral OFC and the PFC during the IGT were
      negatively correlated with total scores on the Hamilton Rating Scale for
      Depression (HAM-D). Although the IGT was useful for differentiating patients with
      BP from control subjects, no significant differences in autonomic activity were
      observed.

PMID- 25978935
TI  - Building Trust.

PMID- 25978936
TI  - Expanding the MDx toolbox for filarial diagnosis and surveillance.
AB  - Filarial parasites are tissue-dwelling nematodes responsible for some of the most
      important neglected tropical diseases. All are transmitted by blood-sucking
      arthropod. Onchocerciasis and lymphatic filariasis in particular are the cause of
      much disfigurement and morbidity. Accurate parasite detection is essential for
      the success of filariasis control programs. The current toolbox for diagnosis and
      surveillance is limited because many of the available tools suffer from lack of
      sensitivity and specificity, and/or are cost-prohibitive. We review the methods
      currently in use and discuss the prospects for developing new molecular
      diagnostic (MDx) tools based on nucleic acid detection. We briefly describe
      recent developments in isothermal nucleic acid amplification and detection, and
      focus on emerging technologies that are field-deployable or suitable for low
      resource settings. 

PMID- 25978937
TI  - A three-way perspective of stoichiometric changes on host-parasite interactions.
AB  - Changes in environmental nutrients play a crucial role in driving disease
      dynamics, but global patterns in nutrient-driven changes in disease are difficult
      to predict. In this paper we use ecological stoichiometry as a framework to
      review host-parasite interactions under changing nutrient ratios, focusing on
      three pathways: (i) altered host resistance and parasite virulence through host
      stoichiometry (ii) changed encounter or contact rates at population level, and
      (iii) changed host community structure. We predict that the outcome of nutrient
      changes on host-parasite interactions depends on which pathways are modified, and
      suggest that the outcome of infection could depend on the overlap in
      stoichiometric requirements of the host and the parasite. We hypothesize that
      environmental nutrient enrichment alters infectivity dynamics leading to
      fluctuating selection dynamics in host-parasite coevolution. 

PMID- 25978938
TI  - Maackia amurensis agglutinin enhances paclitaxel induced cytotoxicity in cultured
      non-small cell lung cancer cells.
AB  - Maackia amurensis agglutinin (MAA) is gaining recognition as the potential
      diagnostic agent for cancer. Previous studies from our laboratory have
      demonstrated that this lectin could interact specifically with the cells and
      biopsy samples of non-small cell lung cancer (NSCLC) origin but not with normal
      lung fibroblast cells. Moreover, this lectin was also found to induce apoptosis
      in NSCLC cells. Further, the biological activity of this lectin was shown to
      survive gastrointestinal proteolysis and inhibit malignant cell growth and
      tumorigenesis in mice model of melanoma thereby indicating the therapeutic
      potential of this lectin. Paclitaxel is one of the widely used traditional
      chemotherapeutic drugs for treatment of NSCLC but it exerts side-effects on
      normal healthy cells too. Studies have revealed that lectins have potential to
      act as an adjuvant chemotherapeutic agent in cancer of different origin. Thus, in
      the present study, an attempt was made to assess the chemo-adjuvant role of MAA
      in three types of NSCLC cell lines [adenocarcinoma cell line (A549), squamous
      cell carcinoma cell line (NCI-H520) and large cell carcinoma cell line (NCI
      H460)]. We have observed that the non-cytotoxic concentration of this lectin was
      able to enhance the cytotoxic activity of Paclitaxel even at low dose by inducing
      apoptosis through intrinsic/mitochondrial pathway in all the three types of NSCLC
      cell lines, although the involvement of extrinsic pathway of apoptosis in case of
      NCI-H460 cell line could not be ruled out. Further, this lectin was also found to
      augment the chemo-preventive activity of this drug by arresting cells in G2-M
      phase of the cell cycle. Collectively, our results have suggested that Maackia
      amurensis agglutinin may have the potential to be used as adjuvant
      chemotherapeutic agent in case of NSCLC. 

PMID- 25978939
TI  - Giant lumbosacral ependymoma.

PMID- 25978940
TI  - Pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular
      dystrophy.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to explore the prevalence,
      nature and scope of pain in adolescents with spinal muscular atrophy and Duchenne
      and Becker muscular dystrophy and whether the pain differs between diagnostic
      groups or between adolescents with different ambulation status. Furthermore to
      study the consequences of pain and to identify pain-exacerbating and pain
      relieving factors. METHODS: In a national survey, fifty-five adolescents with
      spinal muscular atrophy and dystrophinopathy completed a questionnaire assessing
      pain frequency, duration, location using a body map, intensity and discomfort
      using visual analogue scales, pain interference using a modified version of Brief
      Pain Inventory and factors exacerbating and relieving pain. RESULTS: Sixty-nine
      per cent of the adolescents reported pain during the past three months and 50%
      reported chronic pain. The pain prevalence did not differ significantly between
      diagnostic groups or between ambulators and non-ambulators. The average pain
      intensity was graded as mild and the worst pain as moderate. The pain typically
      occurred weekly, most frequently in the neck/back or legs. General activity and
      mood were the areas that were most affected by pain. Common pain-exacerbating
      factors were sitting, too much movement/activity and being lifted or transferred.
      CONCLUSION: Pain is a frequent problem in adolescents with spinal muscular
      atrophy and dystrophinopathy. The assessments used enable an understanding both
      of the nature and scope of pain and of the impact of pain in everyday life. The
      study highlights the importance of assessing pain in a systematic manner and
      offering an individual approach to interventions designed to reduce pain in this
      population.

PMID- 25978941
TI  - Paternal germline mosaicism in collagen VI related myopathies.
AB  - BACKGROUND: Collagen VI-related disorders are a group of muscular diseases
      characterized by muscle wasting and weakness, joint contractures, distal laxity,
      serious respiratory dysfunction and cutaneous alterations, due to mutations in
      the COL6A1, COL6A2 and COL6A3 genes, encoding for collagen VI, a critical
      component of the extracellular matrix. The severe Ullrich congenital muscular
      dystrophy (UCMD) can be due to autosomal recessive mutations in one of the three
      genes with a related 25% recurrence risk. In the majority of UCMD cases
      nevertheless, the underlying mutation is thought to arise de novo and the
      recurrence risk is considered as low. METHODS AND RESULTS: Here we report a
      family with recurrence of UCMD in two half-sibs. In both, the molecular analysis
      revealed heterozygosity for the c.896G > A missense mutation in COL6A1 exon 10
      (Gly299Glu) and for the COL6A1 c.1823-8G > A variation within COL6A1 intron 29.
      The intronic variation was inherited from the father and RNA analysis in skin
      fibroblasts allowed to exclude its role in affecting COL6A1 transcript
      processing. The Gly299Glu mutation occurred apparently de novo in the two sibs.
      CONCLUSION: The described mutational segregation strongly suggests the occurrence
      of paternal germline mosaicism. This is the first report of UCMD recurrence due
      to a germline mosaic COL6 gene mutation. Mosaicism deserves to be considered as
      possible inheritance pattern in genetic counseling and recurrence risk estimation
      in collagen VI-related diseases.

PMID- 25978942
TI  - Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double
      Blind, Randomized Controlled Trial.
AB  - BACKGROUND: Capsaicin specifically activates, and then gradually exhausts, the
      transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in
      neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning
      pain. A natural substance or medication that can reduce the burning pain
      resulting from capsaicin application may have therapeutic potential in
      neuropathic pain. OBJECTIVE: To assess the pain-relieving effects of a mannitol
      containing cream in a capsaicin-based pain model. DESIGN: Randomized, placebo
      controlled, double-blind clinical trial. SETTING: Outpatient pain clinic.
      PARTICIPANTS: Twenty-five adults with pain-free lips. METHODS: Capsaicin .075%
      cream was applied to both halves of each participant's upper lip, inducing pain
      via stimulation of the transient receptor potential vanilloid 1 (TRPV1,
      capsaicin) receptor, then removed after 5 minutes or when participants reported a
      burning pain of 8/10, whichever came first. A cream containing mannitol and the
      same cream without mannitol (control) were then immediately applied, 1 on each
      side of the lip, in an allocation-masked manner. OUTCOME MEASURES: Participants
      self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the
      lip per minute for 10 minutes. A t-test was performed to evaluate the pain score
      change from baseline between each side of the lip at each recording. Area under
      the curve (AUC) analysis was used to determine the overall difference between
      groups. RESULTS: Participants reached a capsaicin-induced pain level of 7.8 +/-
      1.0 points in 3.3 +/- 1.6 minutes that was equal on both sides of the lip. Both
      groups reported progressive diminution of pain over the 10-minute study period.
      However, participants reported significantly reduced pain scores on the mannitol
      cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC
      analysis (P < .001). CONCLUSIONS: Mannitol cream reduced self-reported pain
      scores in a capsaicin pain model more rapidly than a control cream, potentially
      via a TRPV1 receptor effect.

PMID- 25978943
TI  - Effects of Attentional Loadings on Gait Performance Before Turning in Stroke
      Survivors.
AB  - BACKGROUND: Attentional loadings have significant impacts on turning performance
      in individuals with stroke. Improper gait modification before turning may
      contribute to falls after stroke. Therefore, examination of the changes in
      temporal-spatial gait parameters before turning may reveal important deficits in
      gait control when stroke survivors are challenged by dual-tasking. OBJECTIVE: To
      compare the effects of 3 attentional loading conditions on spatial-temporal gait
      parameters before turning between stroke survivors and healthy control subjects.
      DESIGN: Case-control study design. SETTING: University motion analysis
      laboratory. PARTICIPANTS: Ten chronic stroke survivors (mean age = 49 +/- 9
      years) and 10 healthy control subjects (mean age = 53 +/- 5 years) were included.
      METHODS: Spatial-temporal gait parameters were obtained by the use of a motion
      capture system while participants performed the Timed-Up and Go (TUG) test under
      3 attentional loading conditions: single, dual-motor, and dual-cognitive task
      conditions. A repeated-measure analysis of variance was used to analyze the data.
      MAIN OUTCOME MEASURES: We measured gait speed, stride length, and stride time
      during the straight walking phase (one gait cycle before turn) of the TUG test.
      RESULTS: We found that attentional loadings had a differential effect on gait
      speed measured for both groups (P = .001). The dual-motor and dual-cognitive task
      conditions led to a slower gait speed compared with the single-task condition in
      stroke survivors (both P = .02). However, in the TUG scores of healthy control
      subjects, only the dual-cognitive condition led to a significantly reduced gait
      speed compared with the single task condition (P = .001) and dual motor condition
      (P = .01). CONCLUSION: The results demonstrated that attentional loadings
      resulted in a greater deterioration of gait performance before turning in stroke
      survivors compared with healthy control subjects. Particularly, temporal gait
      parameter was more vulnerable to dual-task interference than the spatial gait
      parameter.

PMID- 25978944
TI  - Ultrasound Imaging of Torn Soleus Muscle.

PMID- 25978945
TI  - Diabetic Cranio-Cervico-Radiculoplexus Neuropathy.
AB  - We describe a case of a 53-year-old man with type 2 diabetes mellitus in whom
      cervical-radiculoplexus neuropathy developed, with concomitant cranial and
      phrenic nerve involvement, occurring as a stepwise, monophasic course. The
      patient had a presumed remote history of idiopathic cervical-radiculoplexus
      neuropathy. 

PMID- 25978946
TI  - Men With Late Effects of Polio Decline More Than Women in Lower Limb Muscle
      Strength: A 4-Year Longitudinal Study.
AB  - BACKGROUND: In persons with prior paralytic poliomyelitis, progressive muscle
      weakness can occur after a stable period of at least 15 years. Knowledge is
      limited about which factors influence changes in lower limb muscle strength in
      these persons. OBJECTIVE: To assess changes in lower limb muscle strength
      annually over 4 years in persons with late effects of polio and to identify
      prognostic factors for changes in muscle strength. DESIGN: A prospective,
      longitudinal study. SETTING: University hospital outpatient program.
      PARTICIPANTS: Fifty-two ambulant persons (mean age +/- standard deviation: 64 +/-
      6 years) with verified late effects of polio. METHODS: Mixed linear models were
      used to analyze changes in muscle strength and to identify determinants among the
      following covariates: gender, age, age at acute polio infection, time with late
      effects of polio, body mass index, and estimated baseline muscle weakness. MAIN
      OUTCOME MEASUREMENTS: Knee extensor and flexor and ankle dorsiflexor muscle
      strength were measured annually with a Biodex dynamometer. RESULTS: The men (n =
      28) had significant linear change over time for all knee muscle strength
      measurements, from -1.4% (P < .05) per year for isokinetic knee flexion in the
      less-affected lower limb to -4.2% (P < .001) for isokinetic knee extension in the
      more-affected lower limb, and for 2 ankle dorsiflexor muscle strength
      measurements (-3.3%-1.4% per year [P < .05]). The women (n = 24) had a
      significant linear change over time only for ankle dorsiflexor measurements (4.0%
      5.5% per year [P < .01]). Gender was the strongest factor that predicted a change
      in muscle strength over time. CONCLUSIONS: Over 4 years, men had a greater
      decline in muscle strength than did women, but the rate of decline did not
      accelerate. This finding indicates that gender could be a contributing factor to
      the progressive decline in muscle strength in persons with late effects of polio.

PMID- 25978947
TI  - Physical Education, Exercise, Fitness and Sports: Early PM&R Leaders Build a
      Strong Foundation.

PMID- 25978948
TI  - Functional Outcomes After the Prosthetic Training Phase of Rehabilitation After
      Dysvascular Lower Extremity Amputation.
AB  - OBJECTIVE: To describe physical function outcomes and modes of physical therapy
      intervention for a cohort of patients with dysvascular lower extremity amputation
      (LEA) during the prosthetic training phase of rehabilitation. DESIGN: A
      retrospective cohort study. SETTING: Physical rehabilitation clinics at a
      Veterans Affairs medical center and a university hospital. PATIENTS: Forty-two
      patients (38 men, 4 women, age 60.2 +/- 8.4 years) who completed outpatient
      physical therapy rehabilitation with prosthetic training after dysvascular LEA.
      METHODS: All patients underwent a prosthetic training phase of rehabilitation,
      with standardized outcome measures performed at initiation and discharge. MAIN
      OUTCOME MEASURES: Performance-based physical function measures included Two
      Minute Walk (2 MW), Timed-Up and Go (TUG), and 5-meter gait speed. Self-report
      physical function measures included the Prosthesis Evaluation Questionnaire
      Mobility Section (PEQ-MS) and the Patient-Specific Functional Scale.
      Rehabilitation dose was tracked as total number of clinic visits, rehabilitation
      duration, and specific intervention modes. RESULTS: There were significant
      improvements between initial and discharge values (mean +/- SD) for the Two
      Minute Walk (67.5 +/- 29.9 m and 103.3 +/- 45.8 m, respectively, P < .001), gait
      speed (0.58 +/- 0.27 m/s and 0.88 +/- 0.39 m/s, respectively, P < .001), TUG
      (34.8 +/- 21.3 seconds and 18.6 +/- 13.9 seconds, respectively, P < .001), PEQ-MS
      (2.2 +/- 0.9 and 2.8 +/- 0.8, respectively, P < .001), and Patient-Specific
      Functional Scale (3.2 +/- 2.0 and 5.9 +/- 2.3, respectively, P < .001).
      Performance-based (TUG) and self-report (PEQ-MS) changes in functional mobility
      from initial exam to discharge had low or no correlations with rehabilitation
      dose measures. The number of clinic visits was 12.7 +/- 13.1 and rehabilitation
      duration was 13.7 +/- 16.8 weeks. CONCLUSIONS: Significant improvements in
      performance-based and self-report measures of physical function occurred during
      the prosthetic training phase of physical rehabilitation after dysvascular major
      LEA. Despite improvements in function, gait speed, and TUG outcomes remained
      below clinically important thresholds, indicating patients were limited in
      community ambulation and at risk for falls. Lack of moderate or greater
      correlation between rehabilitation dose and outcome measures may indicate the
      need for more specific rehabilitation dose measures.

PMID- 25978949
TI  - Relationship Between the Kinematics of the Trunk and Lower Extremity and
      Performance on the Y-Balance Test.
AB  - BACKGROUND: The lower quarter Y-balance test (YBT-LQ) has been recommended as a
      measure of dynamic postural control in the clinical setting; however, information
      about the relationship between performance on the YBT-LQ and joint kinematics is
      limited. Thus, the kinematic predictors responsible for performance on the YBT-LQ
      need to be identified for accurate evaluation of dynamic postural control.
      OBJECTIVES: To identify the kinematic predictors that best explain variance in
      performance on the YBT-LQ. DESIGN: Cross-sectional design. SETTING: University
      motion analysis laboratory. PARTICIPANTS: Thirty physically active participants.
      METHODS: All participants performed the YBT-LQ. The kinematics of the trunk and
      lower extremity at maximal reach in each direction of the YBT-LQ were monitored
      using a 3-dimensional motion analysis system. MAIN OUTCOME MEASUREMENTS: The
      correlations between reach distance and joint kinematics were assessed using
      Pearson's correlation coefficient, and the best predictors of performance on the
      YBT-LQ were determined using a stepwise multiple regression analysis. RESULTS:
      Ankle dorsiflexion was the best single predictor of normalized reach in the
      anterior direction of the YBT-LQ (r(2) = 0.50), and the combination of ankle
      dorsiflexion and trunk extension explained 65% of the variance in the anterior
      normalized reach. Hip flexion was the best single predictor of posteromedial
      (r(2) = 0.60) and posterolateral (r(2) = 0.71) normalized reaches of the YBT-LQ.
      The combination of hip flexion and ipsilateral trunk bending and the combination
      of hip flexion and contralateral trunk bending accounted for 69% and 80% of the
      variance in the posteromedial and posterolateral normalized reaches of the YBT
      LQ, respectively. CONCLUSIONS: These findings provide useful information on the
      relative contribution of joint kinematics to performance on the YBT-LQ when
      evaluating dynamic postural control.

PMID- 25978950
TI  - Effect of Fructus Ligustri Lucidi on osteoblastic like cell-line MC3T3-E1.
AB  - Fructus Ligustri Lucidi, fruits of Ligustrum lucidum Ait. (Oleaceae), has the
      effects of tonifying the liver and the kidney and strengthening the bones and
      muscles. In ancient times, Fructus Ligustri Lucidi can be prepared in ethanol or
      in water. Some active compounds have been found in Fructus Ligustri Lucidi, like
      Oleanolic acid and Ursolic acid, and Ursolic acid were proved to have osteogenic
      effects. METHODS AND RESULTS: To prove that Fructus Ligustri Lucidi water extract
      have osteogenic effects on MC3T3-E1 cells and how these effects work, we used CCK
      8 (cell counting kit-8), ELISA (enzyme-linked immunosorbent assay), FQ-PCR
      (realtime fluorescence quantitative PCR) and western blot assays. After treatment
      with Fructus Ligustri Lucidi for 48h, 72h, 96h, the cell viability was marked
      increased, on concentration-dependently and time-dependently pattern. High and
      low concentrations of Fructus Ligustri Lucidi promoted differentiation of cells.
      Fructus Ligustri Lucidi could up-regulate OPG and RANKL protein in supernatant at
      48h and 72h except for highest concentration (10(-1)mg/ml). Fructus Ligustri
      Lucidi promote OPG and RANKL mRNA expression at 48h and 72h, while the level of
      promoting at 72 was higher than 48h. 10(-5)mg/ml of Fructus Ligustri Lucidi up
      regulates OPG protein expression and down-regulates RANKL protein expression.
      After treatment with Fructus Ligustri Lucidi water extract, inhibitors, Fructus
      Ligustri Lucidi water extract with inhibitors for 72h, inhibitors PD 98059, SB
      203580, SP600125 and LY 294002 showed Fructus Ligustri Lucidi-induced cell
      proliferation and the leakage of OPG proteins effects. Fructus Ligustri Lucidi
      promoted the protein levels of ERK, p-ERK, p-JNK, p38, pp38, AKT and p-AKT, and
      inhibited the protein levels of JNK. CONCLUSIONS: Fructus Ligustri Lucidi water
      extract promoted cell proliferation and differentiation, mRNA and protein
      expression of OPG and RANKL on MC3T3-E1 cells. The effects of cell proliferation
      and leakage of OPG related to MAPK and AKT signaling pathways in different ways.

PMID- 25978951
TI  - Study on the anaphylactoid of three phenolic acids in Honeysuckle.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chlorogenic acid (CA) is one of the major
      ingredients in Honeysuckle which exhibits anticancer, antibacterial, antiviral,
      hypoglycemic and anti-HIV activities. However, with the frequent emergence of
      anaphylactoid reactions of traditional Chinese medicine (TCM) injections which
      contains Honeysuckle in recent years, many researchers found that CA exhibited
      allergenicity. AIM OF THE STUDY: To explore the changes of content of CA,
      neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA) during the preparation
      of Honeysuckle and evaluate the anaphylactoid of these three ingredients.
      MATERIALS AND METHODS: Two extracts of Honeysuckle were prepared by different
      methods and the content of CA, NCA and CCA were determined by high performance
      liquid chromatography (HPLC) analysis. Guinea pig and mast cells RBL-2H3 were
      utilized as the animal and cell model to investigate the anaphylactoid of these
      three ingredients. RESULTS: The content of CA decreased while CCA and NCA
      increased during the preparation of Honeysuckle. In vitro and in vivo studies
      showed that CA and CCA could significantly increase the plasma serotonin and beta
      hexosaminidase levels in guinea pigs and induce the degranulation of RBL-2H3
      cell, while NCA did not show such properties. In addition, CAA had a stronger
      effect than CA. CONCLUSION: We believed that both CA and CCA could cause
      anaphylactoid reaction while NCA could not. Moreover, the anaphylactoid of CCA is
      higher than CA. Our result demonstrated that CA is not the only cause of
      anaphylactoid reactions of TCM injections which contains Honeysuckle.

PMID- 25978952
TI  - Aqueous extract of Orostachys japonicus A. Berger exerts immunostimulatory
      activity in RAW 264.7 macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (Crassulaceae)
      (OJ), well-known as Wa-song in Korea is a medicinal plant with immunoregulatory,
      anti-febrile, antidote, and anti-cancer activities. This study was aimed at
      evaluating the immunostimulatory effect of O. japonicus A. Berger and its
      possible mechanisms of action. MATERIALS AND METHODS: To evaluate the effect of
      OJ aqueous extract on macrophage activity, we evaluated the modulation of
      macrophage activation state by observing structural (phagocytic activities) and
      the production of nitric oxide increase. The effect of OJ aqueous extract on
      RAW264.7 cell viability were assessed using Cell Counting Kit (CCK)-8 assay. HPLC
      analysis was performed to identify potential active compounds of this extract.
      RESULTS: The biological investigations indicated that OJ aqueous extract, among
      others, possessed the highest macrophage activation as indicated by NO production
      yield. The results showed that OJ aqueous extract exhibited antioxidant effects,
      which included scavenging activities against DPPH radicals. OJ aqueous extract
      increased the phagocytic activity of RAW 264.7 cells against IgG-opsonized red
      blood cells (RBC). The level of phosphorylated Syk kinase was increased in OJ
      aqueous extract-treated group as compared to control. Phosphorylation of PLC
      gamma was increased in the OJ aqueous extract-treated groups. Quercetin-3-O
      rhamnose and kaempferol-3-O-rhamnose was detected in OJ aqueous extract by HPLC
      analysis. CONCLUSIONS: OJ aqueous extract might play a pivotal ethnopharmacologic
      role as an immunostimulatory agent by promoting Fc gamma receptor (FcgammaR)
      mediated phagocytosis of IgG-opsonized RBCs. On the basis of our results, OJ
      aqueous extract can enhance innate immunity and may serve as an adjuvant for
      tumor treatment.

PMID- 25978953
TI  - An 8-O-4' norlignan exerts oestrogen-like actions in osteoblastic cells via rapid
      nongenomic ER signaling pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sambucus williamsii Hance (SWH), which belongs to
      the Caprifoliaceae family distributed in various regions of China, Korea and
      Japan, has been used as a folk medicine for treatment of bone and joint diseases
      in China for thousands of years. In previous studies, SWH was shown to possess
      anti-osteoporosis, healing fracture, anti-inflammatory and analgesic activities.
      Our previous studies showed that SWH extract effectively suppressed ovariectomy
      induced increase in bone turnover and improved bone mineral density and bone
      biomechanical strength in rats as well as in mice. An 8-O-4' norlignan, (7R,8S)-1
      (4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3
      propanediol (PPD) was previously isolated and identified as the bioactive
      ingredient in SWH. The present study aimed to characterize the bone protective
      effects as well as its mechanism of actions in osteoblasts. MATERIALS AND
      METHODS: Bone protective actions of PPD on different cells were determined by
      proliferation assay, alkaline phosphatase (ALP) activity assay, calcium
      deposition as well as real-time reverse transcriptase-polymerase chain reaction
      (RT-PCR). In addition, estrogen receptor (ER) antagonist ICI182,780 and mitogen
      activated protein kinase kinase (MEK) inhibitor U0126 blocking assays,
      competitive ER radioligand binding assay, ERE-dependent luciferase reporter assay
      and immunoblotting were used to determine if PPD activated ER and if the effects
      of PPD on osteoblastic functions were ER dependent. RESULTS: PPD exerted anabolic
      effects in osteoblasts and its effects were abolished by co-incubation with
      ICI182,780 or U0126. PPD induced mRNA expressions of Runx2, ALP, osteocalcin, and
      increased the ratio of osteoprotegerin/receptor activator of nuclear factor
      kappaB (OPG/RANKL). PPD failed to bind to either ERalpha or ERbeta and did not
      activate ERE-luciferase activity via ER. PPD induced the phosphorylation of
      extracellular regulated kinases (ERK) and its effect was completely abolished by
      U0126. It also induced the phosphorylation of ERalpha at serine 118. CONCLUSION:
      These data show that PPD is a bioactive compound in SWH that exerts oestrogen
      like actions in osteoblast-like cells via ligand-independent, estrogen response
      element (ERE)-independent and mitogen-activated protein (MAP) Kinase-mediated
      rapid nongenomic ER signaling pathway.

PMID- 25978954
TI  - Molecular mechanisms of Polyphyllin I-induced apoptosis and reversal of the
      epithelial-mesenchymal transition in human osteosarcoma cells.
AB  - Osteosarcoma is a most common highly malignant bone tumor in children and
      adolescents. Polyphyllin I (PPI) is an ethanol extraction from Paris polyphylla
      Smith var.yunnanensis (Franch.) Hand.-Mazz, which belongs to antipyretic
      detoxicate family and has been used as a natural medicine in the treatment of
      infectious disease and cancer in China for centuries. The proteasome activity
      inhibitory and anti-osteosarcoma effects of PPI have not been known. Here we
      found PPI exhibited a selective inhibitory effect on proteasomal chymotrypsin
      (CT)-like activity, both in purified human proteasome and in cultured
      osteosarcoma cellular proteasome, and caused an accumulation of ubiquitinated
      proteins. PPI also inhibited viability, proliferation, migration, and invasion of
      MG-63, Saos-2, and U-2 OS osteosarcoma cells and resulted in S phase arrest and
      apoptosis. Furthermore, we explored the molecular targets involved. Exposure of
      osteosarcoma cells to PPI caused an inactivation of the intrinsic nuclear factor
      kappaB (NF-kappaB) and activation of unfolded protein response (UPR)/endoplasmic
      reticulum (ER) stress signaling cascade in osteosarcoma cells, followed by down
      regulation of anti-apoptotic proteins, with up-regulation of pro-apoptotic
      proteins. We also demonstrated down-regulation of c-Myc, Cyclin B1, Cyclin D1,
      and CDK1, which are involved in the cell cycle and growth. Finally, we identified
      down-regulation of Vimentin, Snail, Slug, and up-regulation of E-cadherin, which
      are integral proteins involved in epithelial-mesenchymal transition (EMT). Taken
      together, our data provide insights into the mechanism underlying the anticancer
      activity of PPI in human osteosarcoma cells. 

PMID- 25978955
TI  - Acute and sub-acute oral toxicity of Brazilian red propolis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee product widely used in folk
      medicine due to its numerous pharmacological properties. However, samples from
      different regions can differ in chemical composition, effectiveness, and side
      effects. Despite the widespread use of Brazilian red propolis, which is an
      isoflavone-rich variety, its toxicity has not been carefully studied. AIMS OF THE
      STUDY: To assess the acute and sub-acute toxicity of the hydroethanolic extract
      of red propolis (HERP) administered orally to rats. MATERIALS AND METHODS: HERP
      for the acute (300mg/kg) and sub-acute (10, 100 and 200mg/kg) toxicity studies
      was administered orally to rats according to OECD Guidelines 420 and 407,
      respectively. Clinical signs were identified, and hematological and biochemical
      analyses were performed. Water and food uptake as well as body and organ weights
      of animals were recorded. RESULTS AND CONCLUSIONS: The acute study revealed no
      lethal effects at 300mg/kg of HERP, but toxic signs were observed, as HERP had an
      LD50 of more than 300mg/kg, indicating a warning. The most toxic signals in sub
      acute studies were observed in males at a dose of 200mg/kg HERP. These results
      suggest estrogen-like activity, possibly from the isoflavones in HERP.

PMID- 25978956
TI  - Integrated targeted sphingolipidomics and transcriptomics reveal abnormal
      sphingolipid metabolism as a novel mechanism of the hepatotoxicity and
      nephrotoxicity of triptolide.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook F (TWHF) is a
      traditional herbal medicine in China. Triptolide (TP), the primary bioactive
      compound of TWHF, is an anti-inflammatory and immunosuppressive compound that can
      also injure the liver and kidney. Unfortunately, the toxicity mechanism remains
      unknown. AIM OF THE STUDY: The aim of this study is to understand the regulatory
      role of sphingolipid (SPL) pathways in the TP-induced toxic mechanism in the
      liver and kidney in delayed-type hypersensitivity (DTH) Balb?c mouse. MATERIAL
      AND METHODS: 76 core sphingolipids and 29 species of related metabolic enzymes in
      liver, kidney and plasma were analyzed with previous HPLC-MS/MS and real time
      qPCR method, respectively. Furthermore, the data generated from these two omics
      underwent integrated analysis to describe TP-induced abnormal sphingolipid
      metabolism and identify the specific biomarkers of TP toxicity using
      bioinformation method. RESULTS: High-dose (LD50) TP could induce severe liver and
      kidney injuries. Moreover, TP comprehensively influenced the enzymes involved in
      the sphingolipids metabolism in the liver and kidney at the mRNA expression
      level. Furthermore, the total levels of ceramides (Cers), sphingomyelins (SMs)
      and sphingosine (Sph) were all elevated, while dihydroceramides (dhCers) and
      hexosylceramides (HexCers) were all down-regulated. Several enzymes, including
      kdsr, CerS2, CerS4, CerS5 and CerS6 in the liver and Cerk in the kidney were
      probably responsible for the TP-induced toxic effect, identifying them as
      possible novel therapeutic targets. Besides, fractions of long chain SPL (C16
      C20) exhibited significant increase, and fractions of unsaturated dhCer and Cer
      were significantly changed, both of which above may be due to the change of mRNA
      expression level of CerSs. Moreover, several biomarkers for the diagnosis of TP
      poisoning were discovered. CONCLUSION: In summary, the regulation of SPL
      metabolism uncovered a novel mechanism underlying TP poisoning in the liver and
      kidney. In addition, key biomarkers and enzymes may play an important role in
      reducing the clinical risk associated with the use of TP.

PMID- 25978958
TI  - Parthenolide prodrug LC-1 slows growth of intracranial glioma.
AB  - LC-1 (also known as DMAPT or dimethylamino-parthenolide), a prodrug of
      parthenolide, was tested for anti-proliferative activity against glioma. LC-1 was
      found to have low micromolar cytotoxic activity against three glioma cell lines
      and was also found to be brain penetrant in healthy mice (2.1-3.0 brain-to-plasma
      ratio). In a syngeneic GL261 murine glioma model, LC-1 slowed tumor growth
      kinetics and extended the survival time of tumor-bearing mice in comparison to
      the vehicle control. Consequently, LC-1 represents a promising lead compound for
      further development as a glioma therapy. 

PMID- 25978959
TI  - Therapeutic effects of hybrid liposomes with downregulation of inflammatory
      cytokine for model mice of rheumatoid arthritis in vivo.
AB  - Therapeutic effects of HL for a collagen-induced arthritis (CIA) mouse models of
      HL-23 composed of 95mol% l-alpha-dimyristoylphosphatidylcholine (DMPC) and 5mol%
      polyoxyethylenedodecylether (C12(EO)23) in vivo were examined. Remarkably high
      therapeutic effects of HL-23 for CIA mouse models were obtained on the basis of
      clinical assessment of arthritis. The reduction of hyperplastic synovial membrane
      (pannus tissue) and destruction of the cartilage and bone by HL-23 was revealed
      on the basis of hematoxylin and eosin (HE) and safranin O staining. Furthermore,
      the downregulation of inflammatory cytokines such as interleukin (IL)-1beta,
      tumor necrosis factor (TNF)-alpha, and IL-6 for CIA mouse models treated with HL
      23 were investigated. Remarkably high therapeutic effects without joint swelling
      were obtained in CIA mouse models treated with HL-23. 

PMID- 25978957
TI  - Inhibition of the mevalonate pathway affects epigenetic regulation in cancer
      cells.
AB  - The mevalonate pathway provides metabolites for post-translational modifications
      such as farnesylation, which are critical for the activity of RAS downstream
      signaling. Subsequently occurring regulatory processes can induce an aberrant
      stimulation of DNA methyltransferase (DNMT1) as well as changes in histone
      deacetylases (HDACs) and microRNAs in many cancer cell lines. Inhibitors of the
      mevalonate pathway are increasingly recognized as anticancer drugs. Extensive
      evidence indicates an intense cross-talk between signaling pathways, which affect
      growth, differentiation, and apoptosis either directly or indirectly via
      epigenetic mechanisms. Herein, we show data obtained by novel transcriptomic and
      corresponding methylomic or proteomic analyses from cell lines treated with
      pharmacologic doses of respective inhibitors (i.e., simvastatin, ibandronate).
      Metabolic pathways and their epigenetic consequences appear to be affected by a
      changed concentration of NADPH. Moreover, since the mevalonate metabolism is part
      of a signaling network, including vitamin D metabolism or fatty acid synthesis,
      the epigenetic activity of associated pathways is also presented. This emphasizes
      the far-reaching epigenetic impact of metabolic therapies on cancer cells and
      provides some explanation for clinical observations, which indicate the
      anticancer activity of statins and bisphosphonates. 

PMID- 25978960
TI  - Isolation, semi-synthesis and bio-evaluation of spatane derivatives from the
      brown algae Stoechospermum marginatum.
AB  - A comprehensive investigation of chemical constituents from brown algae
      Stoechospermum marginatum yielded ten known spatane compounds (1-10). To develop
      the compound libraries on these scaffolds, a series of semi synthetic derivatives
      was prepared (1a-1d, 2a, 4a, 11 and 12) and investigated for their anti-microbial
      and anticancer activities. The results indicated that compounds 2a, 4, 1b and 4a
      exhibited potent cytotoxic activities against B16F10 cancer cell line with IC50
      values of 3.28, 3.45, 3.62 and 4.11 MUg/ml respectively, which are comparable to
      the standard drug (etoposide IC50=4.12 MUg/ml). In addition, 4 and 1b were also
      manifested potent antimicrobial activities against tested bacterial and fungal
      strains. This is the first Letter on the synthesis and biological activities of
      these novel derivatives.

PMID- 25978961
TI  - Synthesis and anti-inflammatory activity of new 1,2,4-triazole derivatives.
AB  - The series of new 1,2,4-triazole derivatives with methacrylic acid moiety were
      synthesized and characterized by NMR and IR spectroscopy as well as X-ray
      crystallography. The influence of newly synthesized compounds on the inflammation
      on the level of cytokine production and the proliferation of human peripheral
      blood mononuclear cells (PBMC) were experimentally evaluated. Obtained triazoles
      showed antiproliferative activity and diverse effects on cytokine production. Two
      compounds demonstrated potentially anti-inflammatory activity and comparable
      effects with ibuprofen. 

PMID- 25978962
TI  - Separation and peroxisome proliferator-activated receptor-gamma agonist activity
      evaluation of synthetic racemic bavachinin enantiomers.
AB  - Bavachinin, isolated from Psoralea corylifolia seeds, has been reported to
      demonstrate peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist
      activity. However, isolated bavachinin is actually a mixture of S and R
      configurations, with an enantiomeric excess value of approximately 24.3%. For
      further study on the structure-activity relationships of bavachinin,
      investigating the PPAR-gamma agonist activity of the two enantiomers is crucial.
      Considering the limited availability, racemic bavachinin was prepared in this
      study using chemical synthesis. The enantiomers of racemic bavachinin were then
      separated using supercritical fluid chromatography. This concise strategy yielded
      (S)- and (R)-bavachinin in optical purity as high as ?97.5%. The PPAR-gamma
      agonist activity of the two enantiomers was evaluated using a time-resolved
      fluorescence resonance energy transfer-based competitive binding assay method;
      IC50 values of (S)- and (R)-bavachinin were 616.7 and 471.2 nM, respectively. The
      interaction between the compounds and PPAR-gamma was further explored using a
      molecular docking method. This study suggests that (S)- and (R)-bavachinin
      demonstrate similar PPAR-gamma agonist activities.

PMID- 25978963
TI  - Hydroxy tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial
      topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of RHS moiety
      (Part-3).
AB  - Novel bacterial topoisomerase inhibitors (NBTIs) are a new class of broad
      spectrum antibacterial agents targeting bacterial Gyrase A and ParC and have
      potential utility in combating antibiotic resistance. (R)-Hydroxy-1,5
      naphthyridinone left-hand side (LHS) oxabicyclooctane linked pyridoxazinone right
      hand side (RHS) containing NBTIs showed a potent Gram-positive antibacterial
      profile. SAR around the RHS moiety, including substitutions around
      pyridooxazinone, pyridodioxane, and phenyl propenoids has been described. A
      fluoro substituted pyridoxazinone showed an MIC against Staphylococcus aureus of
      0.5 MUg/mL with reduced functional hERG activity (IC50 333 MUM) and good in vivo
      efficacy [ED90 12 mg/kg, intravenous (iv) and 15 mg/kg, oral (p.o.)]. A
      pyridodioxane-containing NBTI showed a S. aureus MIC of 0.5 MUg/mL, significantly
      improved hERG IC50 764 MUM and strong efficacy of 11 mg/kg (iv) and 5 mg/kg
      (p.o.). A phenyl propenoid series of compounds showed potent antibacterial
      activity, but also showed potent hERG binding activity. Many of the compounds in
      the hydroxy-tricyclic series showed strong activity against Acinetobacter
      baumannii, but reduced activity against Escherichia coli and Pseudomonas
      aeruginosa. Bicyclic heterocycles appeared to be the best RHS moiety for the
      hydroxy-tricyclic oxabicyclooctane linked NBTIs.

PMID- 25978964
TI  - Identification of indole inhibitors of human hematopoietic prostaglandin D2
      synthase (hH-PGDS).
AB  - Human H-PGDS has shown promise as a potential target for anti-allergic and anti
      inflammatory drugs. Here we describe the discovery of a novel class of indole
      inhibitors, identified through focused screening of 42,000 compounds and
      evaluated using a series of hit validation assays that included fluorescence
      polarization binding, 1D NMR, ITC and chromogenic enzymatic assays. Compounds
      with low nanomolar potency, favorable physico-chemical properties and inhibitory
      activity in human mast cells have been identified. In addition, our studies
      suggest that the active site of hH-PGDS can accommodate larger structural
      diversity than previously thought, such as the introduction of polar groups in
      the inner part of the binding pocket. 

PMID- 25978965
TI  - Discovery of beta-D-2'-deoxy-2'-alpha-fluoro-4'-alpha-cyano-5-aza-7,9-dideaza
      adenosine as a potent nucleoside inhibitor of respiratory syncytial virus with
      excellent selectivity over mitochondrial RNA and DNA polymerases.
AB  - Novel 4'-substituted beta-d-2'-deoxy-2'-alpha-fluoro (2'd2'F) nucleoside
      inhibitors of respiratory syncytial virus (RSV) are reported. The introduction of
      4'-substitution onto 2'd2'F nucleoside analogs resulted in compounds
      demonstrating potent cell based RSV inhibition, improved inhibition of the RSV
      polymerase by the nucleoside triphosphate metabolites, and enhanced selectivity
      over incorporation by mitochondrial RNA and DNA polymerases. Selectivity over the
      mitochondrial polymerases was found to be extremely sensitive to the specific 4'
      substitution and not readily predictable. Combining the most potent and selective
      4'-groups from N-nucleoside analogs onto a 2'd2'F C-nucleoside analog resulted in
      the identification of beta-D-2'-deoxy-2'-alpha-fluoro-4'-alpha-cyano-5-aza-7,9
      dideaza adenosine as a promising nucleoside lead for RSV.

PMID- 25978966
TI  - Development of a novel class of potent and selective FIXa inhibitors.
AB  - Using structure based drug design (SBDD), a novel class of potent coagulation
      Factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over
      FXa inhibition was achieved. Selected compounds demonstrated oral bioavailability
      in rat IV/PO pharmacokinetic (PK) studies. Finally, the pharmacodynamics (PD) of
      this class of molecules was evaluated in Thrombin Generation Assay (TGA) in Corn
      Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of
      a FIXa inhibitor. 

PMID- 25978967
TI  - Persistent depression doubles stroke risk despite treatment, study finds.

PMID- 25978968
TI  - Mineralocorticoid exposure and receptor activity modulate microvascular
      endothelial function in African Americans with and without hypertension.
AB  - Prior work suggests blood pressure in African Americans is more sensitive to the
      effects of aldosterone than in Caucasians. This mechanism may relate to a
      negative response of the vascular endothelium to aldosterone, including reduced
      glucose-6-phosphate dehydrogenase (G6PD) activity. Thirty-three African Americans
      (11 hypertensives, 22 controls) without evidence of diabetes or metabolic
      syndrome completed the protocol. The protocol included measurement of in vivo
      microvascular endothelial function by digital pulse arterial tonometry and ex
      vivo measurement of endothelial function by videomicroscopy of arterioles
      obtained from these same subjects with and without exposure to aldosterone or
      spironolactone. Systemic and arteriolar G6PD activities were also measured. In
      vivo and ex vivo microvascular endothelial function were impaired in African
      Americans with hypertension. One-hour exposure with aldosterone impaired
      endothelium-dependent vasodilation in arterioles from normotensive subjects,
      while 1 hour of spironolactone exposure reversed endothelial dysfunction in
      arterioles from hypertensive subjects. G6PD activity was impaired in hypertensive
      arterioles. Aldosterone-related endothelial dysfunction may be responsible for at
      least a portion of the greater blood pressure sensitivity to aldosterone in
      African Americans. This may be in part related to vascular suppression of G6PD
      activity. 

PMID- 25978970
TI  - Exopolysaccharide assay in Escherichia coli microcolonies using a cleavable
      fusion protein of GFP-labeled carbohydrate-binding module.
AB  - A fused protein composed of a carbohydrate-binding module and green fluorescence
      protein (GFP) was developed to measure the exopolysaccharides (EPShs) present in
      Escherichia coli microcolonies. The cleavage of the GFP part of this protein
      using a site-specific protease allowed for the non-invasive and quantitative
      evaluation of the EPShs. 

PMID- 25978969
TI  - Increased CSF Abeta during the very early phase of cerebral Abeta deposition in
      mouse models.
AB  - Abnormalities in brains of Alzheimer's disease (AD) patients are thought to start
      long before the first clinical symptoms emerge. The identification of affected
      individuals at this 'preclinical AD' stage relies on biomarkers such as decreased
      levels of the amyloid-beta peptide (Abeta) in the cerebrospinal fluid (CSF) and
      positive amyloid positron emission tomography scans. However, there is little
      information on the longitudinal dynamics of CSF biomarkers, especially in the
      earliest disease stages when therapeutic interventions are likely most effective.
      To this end, we have studied CSF Abeta changes in three Abeta precursor protein
      transgenic mouse models, focusing our analysis on the initial Abeta deposition,
      which differs significantly among the models studied. Remarkably, while we
      confirmed the CSF Abeta decrease during the extended course of brain Abeta
      deposition, a 20-30% increase in CSF Abeta40 and Abeta42 was found around the
      time of the first Abeta plaque appearance in all models. The biphasic nature of
      this observed biomarker changes stresses the need for longitudinal biomarker
      studies in the clinical setting and the search for new 'preclinical AD'
      biomarkers at even earlier disease stages, by using both mice and human samples.
      Ultimately, our findings may open new perspectives in identifying subjects at
      risk for AD significantly earlier, and in improving the stratification of
      patients for preventive treatment strategies. 

PMID- 25978971
TI  - Impact of Diabetes on the Protective Role of FOXO1 in Wound Healing.

PMID- 25978972
TI  - Rcan1-1L overexpression induces mitochondrial autophagy and improves cell
      survival in angiotensin II-exposed cardiomyocytes.
AB  - Mitochondrial autophagy is an important adaptive stress response and can be
      modulated by various key molecules. A previous study found that the regulator of
      calcineurin 1-1L (Rcan1-1L) may regulate mitochondrial autophagy and cause
      mitochondria degradation in neurocytes. However, the effect of Rcan1-1L on
      cardiomyocytes has not been determined. In the present study, we aimed to
      investigate the role of Rcan1-1L in angiotensin II (Ang II)-exposed human
      cardiomyocytes. Above all, Human adult cardiac myocytes (HACMs) were exposed to
      200nmol/L Ang II for 4 days. Enhanced H2O2 production, cytochrome C release and
      mitochondrial permeability were observed in these cells, which were blocked by
      valsartan. Consistently, Ang II exposure significantly reduced cardiomyocyte
      viability. However, transfection of Rcan1-1L vector promoted cell viability and
      ameliorated the apoptosis caused by Ang II. Rcan1-1L clearly promoted
      mitochondrial autophagy in HACMs, with elevated autophagy protein (ATG) 5 and
      light chain 3 (LC3) expression. Transient mitochondrial biogenesis and reduced
      cytochrome C release was also induced by Rcan1-1L. Additionally, Rcan1-1L
      significantly inhibited calcineurin/nuclear factor of activated T cells (NFAT)
      signaling. We thus conclude that Rcan1-1L may play a protective role in Ang II
      treated cardiomyocytes through the induction of mitochondrial autophagy, and may
      be an alternative method of cardiac protection. 

PMID- 25978973
TI  - Bone marrow mononuclear cell transplantation improves mitochondrial bioenergetics
      in the liver of cholestatic rats.
AB  - Mitochondrial dysfunction has been associated with liver cholestatis. Toxic bile
      salt accumulation leads to chronic injury with mitochondrial damage, ROS increase
      and apoptosis, resulting in liver dysfunction. This study aimed to analyze
      mitochondrial bioenergetics in rats with hepatic fibrosis induced by bile duct
      ligation (BDL) after BMMNC transplantation. Livers were collected from normal
      rats, fibrotic rats after 14 and 21 days of BDL (F14d and F21d) and rats that
      received BMMNC at 14 days of BDL, analyzed after 7 days. F21d demonstrated
      increased collagen I content and consequently decrease after BMMNC
      transplantation. Both F14d and F21d had significantly reduced mitochondrial
      oxidation capacity and increased mitochondrial uncoupling, which were restored to
      levels similar to those of normal group after BMMNC transplantation. In addition,
      F21d had a significantly increase of UCP2, and reduced PGC-1alpha content.
      However, after BMMNC transplantation both proteins returned to levels similar to
      normal group. Moreover, F14d had a significantly increase in 4-HNE content
      compared to normal group, but after BMMNC transplantation 4-HNE content
      significantly reduced, suggesting oxidative stress reduction. Therefore, BMMNC
      transplantation has a positive effect on hepatic mitochondrial bioenergetics of
      cholestatic rats, increasing oxidative capacity and reducing oxidative stress,
      which, in turn, contribute to liver function recover. 

PMID- 25978974
TI  - Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in
      cell proliferation and migration.
AB  - According to the multifactorial model of cervical cancer (CC) causation, it is
      now recognized that other modifications, in addition to Human papillomavirus
      (HPV) infection, are necessary for the development of this neoplasia. Among
      these, it has been proposed that a dysregulation of the WNT pathway might favor
      malignant progression of HPV-immortalized keratinocytes. The aim of this study
      was to identify components of the WNT pathway differentially expressed in CC vs.
      non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A
      expression was found strongly downregulated in cell lines and biopsies derived
      from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene
      delivery system or after adding a recombinant human protein decreases cell
      proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly
      accelerates proliferation. Decreased WNT7A expression was due to hypermethylation
      at particular CpG sites. To our knowledge, this is the first study reporting
      reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration
      negatively affects cell proliferation and migration. 

PMID- 25978975
TI  - Sentinel lymph node biopsy followed by lymph node dissection for localised
      primary cutaneous melanoma.
AB  - BACKGROUND: Melanoma is the leading cause of skin cancer-associated mortality.
      The vast majority of newly diagnosed melanomas are confined to the primary
      cutaneous site. Surgery represents the mainstay of melanoma treatment. Treatment
      strategies include wide excision of the primary tumour and sentinel lymph node
      biopsy (SLNB) to assess the status of the regional nodal basin(s). SLNB has
      become an important component of initial melanoma management providing accurate
      disease staging. OBJECTIVES: To assess the effects and safety of SLNB followed by
      completion lymph node dissection (CLND) for the treatment of localised primary
      cutaneous melanoma. SEARCH METHODS: We searched the following databases up to
      February 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library (2015, Issue 1),
      MEDLINE (from 1946), EMBASE (from 1974), and LILACS ((Latin American and
      Caribbean Health Science Information database, from 1982). We also searched the
      following from inception: African Index Medicus, IndMED of India, Index Medicus
      for the South-East Asia Region, and six trials registers. We checked the
      reference lists of included and excluded studies for further references to
      relevant randomised controlled trials (RCTs). We searched ISI Web of Science
      Conference Proceedings from inception to February 2015, and we scanned the
      abstracts of major dermatology and oncology conference proceedings up to 2015.
      SELECTION CRITERIA: Two review authors independently assessed all RCTs comparing
      SLNB followed by CLND for the treatment of primary localised cutaneous melanoma
      for inclusion. Primary outcome measures were overall survival and rate of
      treatment complications and side effects. DATA COLLECTION AND ANALYSIS: Two
      review authors independently extracted and analysed data on survival and
      recurrence, assessed risk of bias, and collected adverse effect information from
      included trials. MAIN RESULTS: We identified and included a single eligible trial
      comparing SLNB with observation and published in eight different reports (from
      2005 to 2014) with 2001 participants. This did not report on our first primary
      outcome of overall survival. The study did report on the rate of treatment
      complications. Our secondary outcomes of disease-specific and disease-free
      survival, local recurrence and distant metastases were reported. There were 1347
      participants in the intermediate-thickness melanoma group and 314 in the thick
      melanoma group.With regard to treatment complications, short-term surgical
      morbidity (30 days) in 1735 participants showed no difference between SLNB and
      observation (risk ratio [RR] 1.11; 95% confidence interval [CI] 0.9 to 1.37) for
      wide excision of the tumour site but favoured observation for complications
      related to the regional nodal basin (RR 14.36; 95% CI 6.74 to 30.59).The study
      did not report the actual 10-year melanoma-specific survival rate for all
      included participants. Instead, melanoma-specific survival rates for each group
      of participants: intermediate-thickness melanoma (defined as 1.2 to 3.5 mm) and
      thick melanomas (defined as 3.50 mm or more) was reported.In the intermediate
      thickness melanoma group there was no statistically significant difference in
      disease-specific survival between study groups at 10 years (81.4 +/- 1.5% versus
      78.3 +/- 2.0%, hazard ratio [HR] 0.84; 95% CI 0.65 to 1.09). In the thick
      melanoma group, again there was no statistically significant difference in
      disease-specific survival between study groups at 10 years (58.9.3 +/- 4.1%
      versus 64.4 +/- 4.6%, HR 1.12; 95% CI 0.77 to 1.64). Combining these groups there
      was some heterogeneity (I2 = 34%) but the total HR was not statistically
      significant (HR 0.92; 95% CI 0.74 to 1.14). This study failed to show any
      difference for its stated primary outcome.The summary estimate for disease-free
      survival at 10 years favoured SLNB over observation in participants with
      intermediate-thickness and thick melanomas (HR 0.75; 95% CI 0.63 to 0.89).With
      regard to the rate of local and regional recurrence as the site of first
      recurrence, a benefit of SLNB uniformly existed in both groups of participants
      with intermediate-thickness and thick melanomas (RR 0.56; 95% CI 0.45 to 0.69).
      This is in contrast with a uniformly unfavourable effect of SLNB with regard to
      the rate of distant metastases as site of first recurrence, in both groups of
      participants with intermediate-thickness and thick melanomas (HR 1.33; 95% CI
      1.03 to 1.72). AUTHORS' CONCLUSIONS: We contacted the trial authors querying the
      lack of data on overall survival which was the primary outcome of their important
      study. They stated "there are numerous additional analyses that have yet to be
      reported for the trial". We expect that overall survival data will be available
      in a future update of this review.Disease-free survival and rate of local and
      regional recurrence favoured SLNB in both groups of participants with
      intermediate-thickness and thick melanomas but short-term surgical morbidity was
      higher in the SLNB group, especially with regard to complications in the nodal
      basin.The evidence for the outcomes of interest in this review is of low quality
      due to the risk of bias and imprecision of the estimated effects. Further
      research may have an important impact on our estimate of the effectiveness of
      SLNB in managing primary localised cutaneous melanoma. Currently this evidence is
      not sufficient to document a benefit of SLNB when compared to observation in
      individuals with primary localised cutaneous melanoma.

PMID- 25978976
TI  - First discovery of colobine fossils from the Late Miocene/Early Pliocene in
      central Myanmar.
AB  - Here we report two kinds of colobine fossils discovered from the latest
      Miocene/Early Pliocene Irrawaddy sediments of the Chaingzauk area, central
      Myanmar. A left mandibular corpus fragment preserving M1-3 is named as a new
      genus and species, Myanmarcolobus yawensis. Isolated upper (M(1)?) and lower (M2)
      molars are tentatively identified as Colobinae gen. et sp. indet. Although both
      forms are medium-sized colobines, they are quite different from each other in M2
      morphology. The isolated teeth of the latter show typical colobine-type features,
      so it is difficult to identify their taxonomic position, whereas lower molars of
      Myanmarcolobus have unique features, such as a trapezoid-shaped long median
      lingual notch, a deeply concave median buccal cleft, a strongly developed
      mesiobuccal notch, and rather obliquely running transverse lophids. Compared with
      fossil and living Eurasian colobine genera, Myanmarcolobus is most similar in
      lower molar morphology to the Pliocene Dolichopithecus of Europe rather than to
      any Asian forms. In Dolichopithecus, however, the tooth size is much larger and
      the median lingual notch is mesiodistally much shorter than that of
      Myanmarcolobus. The discovery of Myanmarcolobus in central Myanmar is the oldest
      fossil record in Southeast Asia not only of colobine but also of cercopithecid
      monkeys and raises many questions regarding the evolutionary history of Asian
      colobine monkeys. 

PMID- 25978977
TI  - Analysis of long-term survival following transcatheter aortic valve implantation
      from a single high-volume center.
AB  - Mortality after transcatheter aortic valve implantation (TAVI) has been reported
      to range up to 3 years. However, long-term mortality remains underexplored. The
      aims of this study were to determine long-term mortality in patients who undergo
      TAVI and to identify correlates of long-term death. From a single institution's
      prospectively collected TAVI database, all patients who underwent TAVI with a
      maximum follow-up duration of 5 years were analyzed. The population was analyzed
      on the basis of access route (transapical TAVI or transfemoral TAVI). Cox
      regression and Kaplan-Meier survival analysis were conducted. A total of 511
      patients who underwent TAVI were included in the analysis (transapical TAVI n =
      115, transfemoral TAVI n = 396). The mean Society of Thoracic Surgeons score was
      9.6 +/- 4. Mortality at 30 days (18% vs 6%, p <0.001) and 1 year (32% vs 21%, p
      <0.01) was significantly increased in the transapical TAVI group. Long-term
      survival probability was <50% for the 2 approaches (log-rank p = 0.33). Vascular
      complications (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.38 to 3.33,
      p = 0.001), more than mild aortic insufficiency (HR 1.81, 95% CI 1.15 to 2.83, p
      = 0.01), atrial fibrillation (HR 1.87, 95% CI 1.36 to 2.57, p <0.001), and in
      hospital stroke (HR 2.35, 95% CI 1.39 to 4.00, p = 0.002) were independently
      associated with long-term death. The survival probability of patients at high
      surgical risk versus those who were inoperable was similar in the long term (log
      rank p = 0.53). In conclusion, the overall long-term survival of patients with
      aortic stenosis who were approved to undergo TAVI was <50% irrespective of access
      method. Strategies geared toward reducing in-hospital stroke, vascular
      complications, and aortic regurgitation are still needed, as these variables are
      correlates of long-term mortality.

PMID- 25978978
TI  - A risk score for predicting 1-year mortality in patients >=75 years of age
      presenting with non-ST-elevation acute coronary syndrome.
AB  - Approximately 1/3 of patients with non-ST-segment elevation (NSTE) acute coronary
      syndromes (ACS) are >=75 years of age. Risk stratification in these patients is
      generally difficult because supporting evidence is scarce. The investigators
      developed and validated a simple risk prediction score for 1-year mortality in
      patients >=75 years of age presenting with NSTE ACS. The derivation cohort was
      the Italian Elderly ACS trial, which included 313 patients with NSTE ACS aged
      >=75 years. A logistic regression model was developed to predict 1-year
      mortality. The validation cohort was a registry cohort of 332 patients with NSTE
      ACS meeting the same inclusion criteria as for the Italian Elderly ACS trial but
      excluded from the trial for any reason. The risk score included 5 statistically
      significant covariates: previous vascular event, hemoglobin level, estimated
      glomerular filtration rate, ischemic electrocardiographic changes, and elevated
      troponin level. The model allowed a maximum score of 6. The score demonstrated a
      good discriminating power (C statistic = 0.739) and calibration, even among
      subgroups defined by gender and age. When validated in the registry cohort, the
      scoring system confirmed a strong association with the risk for all-cause death.
      Moreover, a score >=3 (the highest baseline risk group) identified a subset of
      patients with NSTE ACS most likely to benefit from an invasive approach. In
      conclusion, the risk for 1-year mortality in patients >=75 years of age with NSTE
      ACS is substantial and can be predicted through a score that can be easily
      derived at the bedside at hospital presentation. The score may help in guiding
      treatment strategy. 

PMID- 25978979
TI  - Aberrant movement of beta-tropomyosin associated with congenital myopathy causes
      defective response of myosin heads and actin during the ATPase cycle.
AB  - We have investigated the effect of the E41K, R91G, and E139del beta-tropomyosin
      (TM) mutations that cause congenital myopathy on the position of TM and
      orientation of actin monomers and myosin heads at different mimicked stages of
      the ATPase cycle in troponin-free ghost muscle fibers by polarized fluorimetry. A
      multi-step shifting of wild-type TM to the filament center accompanied by an
      increase in the amount of switched on actin monomers and the strongly bound
      myosin heads was observed during the ATPase cycle. The R91G mutation shifts TM
      further towards the inner and outer domains of actin at the strong- and weak
      binding stages, respectively. The E139del mutation retains TM near the inner
      domains, while the E41K mutation captures it near the outer domains. The E41K and
      R91G mutations can induce the strong binding of myosin heads to actin, when TM is
      located near the outer domains. The E139del mutation inhibits the amount of
      strongly bound myosin heads throughout the ATPase cycle. 

PMID- 25978980
TI  - Biochemistry and regulatory functions of bacterial glucose kinases.
AB  - Glucokinases (Glks) are enzymes widely distributed in all three domains of life.
      They are located at the beginning of the glycolytic pathway and are responsible
      for the glucose phosphorylation from various phosphate group donors such as ATP,
      ADP and polyphosphate. So far, there are eight crystallized Glks, and at least
      one belongs to each of the three reported Glk families. Structural studies have
      elucidated the mechanism for Glk action and multimerization. Cloning,
      overexpression and biochemical characterization have demonstrated the wide
      diversity of these enzymes. As reported for various microorganisms, in addition
      to their catalytic activity, some Glks, possessing ROK (Repressor Orf Kinases)
      motifs, also display a regulatory role. This function has been associated to the
      mechanisms of carbon catabolite regulation, morphological differentiation and
      antibiotic production. The present review covers the classification, detailed
      tertiary structure, mechanism of action, biochemical characterization and some
      regulatory aspects of bacterial Glks. 

PMID- 25978982
TI  - Leukemoid reaction to Clostridium difficile infection.
AB  - Clostridium difficile infections (CDI) are increasing in incidence and severity.
      Leukemoid reaction is rarely seen with CDI, and indicates severe disease with
      grave prognosis. We present an elderly female who developed leukemoid reaction in
      response to CDI. The patient died despite early antibiotic therapy with surgical
      evaluation. 

PMID- 25978981
TI  - Association between the aldehyde dehydrogenase 2*2 allele and smoking-related
      chronic airway obstruction in a Japanese general population: a pilot study.
AB  - Aldehyde dehydrogenase 2 (ALDH2) detoxifies exogenous and endogenous toxic
      aldehydes; however, its protective effect against cigarette smoke in airways is
      unknown. We therefore examined whether the inactive ALDH2*2 allele is associated
      with smoking-related chronic airway obstruction. We conducted a cross-sectional
      study including 684 Japanese participants in a health screening program, and a
      retrospective longitudinal study in the elderly subgroup. The risks of airway
      obstruction in the ever-smokers with the ALDH2*1/*2 and *2/*2 genotypes were two
      and three times higher, respectively, than in the never-smokers with the
      ALDH2*1/*1 genotype. Moreover, the combined effect of smoking and the ALDH2*2
      allele was prominent in the asthmatic subjects. In a longitudinal association
      analysis, the combination of the ALDH2 genotype and pack-years of smoking
      synergistically increased the risk of airway obstruction. The number of pack
      years of smoking at baseline was identified to be a significant predictor of
      airway obstruction only in the ALDH2*2 allele carriers. In addition, the ALDH2*2
      allele was also associated with the incidence of smoking-related airway
      obstruction, in the Cox proportional hazards model. This pilot study demonstrated
      for the first time a significant gene-environment interaction between the ALDH2*2
      allele and cumulative exposure to cigarette smoke on the risk of airway
      obstruction.

PMID- 25978983
TI  - What's in a name?

PMID- 25978985
TI  - Know your target, know your molecule.

PMID- 25978986
TI  - Layers of structure and function in protein aggregation.

PMID- 25978987
TI  - Voices of chemical biology.

PMID- 25978994
TI  - Membrane fusion: A new role for lipid domains?

PMID- 25978995
TI  - Enzyme pathways: C1 metabolism redesigned.

PMID- 25978996
TI  - Application guide for omics approaches to cell signaling.
AB  - Research in signal transduction aims to identify the functions of different
      signaling pathways in physiological and pathological states. Traditional
      techniques using biochemical, genetic or cell biological approaches have made
      important contributions to our understanding of cellular signaling. However, the
      single-gene approach does not take into account the full complexity of cell
      signaling. With the availability of omics techniques, great progress has been
      made in understanding signaling networks. Omics approaches can be classified into
      two categories: 'molecular profiling', including genomic, proteomic, post
      translational modification and interactome profiling; and 'molecular
      perturbation', including genetic and functional perturbations. 

PMID- 25978998
TI  - Density, Demography, and Influential Environmental Factors on Overwintering
      Populations of Sogatella furcifera (Hemiptera: Delphacidae) in Southern Yunnan,
      China.
AB  - Sogatella furcifera (Horvath) (Hemiptera: Delphacidae) is the most serious pest
      on rice in southwestern China. Yunnan province is within this region and is a
      major overwintering area for S. furcifera in China. This field study was carried
      out over 4 yr (2010-2013) and focused on S. furcifera distribution, population
      density, and demography, as well as the relationship between various
      environmental factors and the distribution and density of overwintering S.
      furcifera in Yunnan. Our study demonstrated that overwintering populations of S.
      furcifera mainly occurred in valleys and lowlands below 25.02 degrees N and 1,608
      m above sea level (a.s.l.), where ratooning rice was present [corrected]. The
      overwintering range of S. furcifera has expanded in Yunnan compared with 20 yr
      ago, and regional climate change is believed to be the main contributing cause
      for this expansion. Environmental factor analysis showed that the mean air
      temperature of the coldest quarter and precipitation of the coldest quarter were
      two key factors that were strongly linked to the overwintering distribution and
      density of S. furcifera in Yunnan. Wintertime temperature was the principal
      influencing factor to determine the distribution and density of S. furcifera,
      while the effect of precipitation was indirect in that it influenced the insect's
      distribution via its host. This study documented the major overwintering areas of
      S. furcifera in Yunnan, which can be used to predict outbreak potential in the
      following spring. Hence, key climatic factors, overwintering distribution, and
      density of S. furcifera should be used when forecasting outbreaks in spring.

PMID- 25978997
TI  - Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous
      loss of epithelial phenotype in human solid tumor cells.
AB  - Stage-specific embryonic antigen-4 (SSEA-4) is a glycosphingolipid, which is
      overexpressed in some cancers and has been linked to disease progression.
      However, little is known about the functions of SSEA-4 and the characteristics of
      SSEA-4 expressing tumor cells. Our studies identified SSEA-4 expression on a
      subpopulation of cells in many solid tumor cell lines but not in leukemic cell
      lines. Fluorescence-activated cell sorting-sorted SSEA-4(+) prostate cancer cells
      formed fibroblast-like colonies with limited cell-cell contacts, whereas SSEA-4(
      ) cells formed cobblestone-like epithelial colonies. Only colonies derived from
      SSEA-4(+) cells were enriched for pluripotent embryonic stem cell markers.
      Moreover, major epithelial cell-associated markers Claudin-7, E-cadherin, ESRP1
      and GRHL2 were down-regulated in the SSEA-4(+) fraction of DU145 and HCT-116
      cells. Similar to cell lines, SSEA-4(+) primary prostate tumor cells also showed
      down-regulation of epithelial cell-associated markers. In addition, they showed
      up-regulation of epithelial-to-mesenchymal transition as well as mesenchymal
      markers. Furthermore, SSEA-4(+) cells escape from adhesive colonies spontaneously
      and form invadopodia-like migratory structures, in which SSEA-4, cortactin as
      well as active pPI3K, pAkt and pSrc are enriched and colocalized. Finally, SSEA
      4(+) cells displayed strong tumorigenic ability and stable knockdown of SSEA-4
      synthesis resulted in decreased cellular adhesion to different extracellular
      matrices. In conclusion, we introduce SSEA-4 as a novel marker to identify
      heterogeneous, invasive subpopulations of tumor cells. Moreover, increased cell
      surface SSEA-4 expression is associated with the loss of cell-cell interactions
      and the gain of a migratory phenotype, suggesting an important role of SSEA-4 in
      cancer invasion by influencing cellular adhesion to the extracellular matrix. 

PMID- 25978999
TI  - Soil microarthropods and their relationship to higher trophic levels in the
      Pedregal de San Angel Ecological Reserve, Mexico.
AB  - Soil fauna is essential for ecosystem dynamics as it is involved in
      biogeochemical processes, promotes nutrient availability, and affects the animal
      communities associated with plants. In this study, we examine the possible
      relationship between the soil microarthropod community on foliage production and
      quality of the shrub Pittocaulon praecox. We also examine the arthropods
      associated to its foliage, particularly the size of the main herbivores and of
      their natural enemies, at two sites with contrasting vegetation cover and
      productivity. The diversity of soil microarthropods was assessed from soil
      samples collected monthly under P. praecox individuals over 13 mo. Specimens
      collected were identified to species or morphospecies. Shrub foliage productivity
      was evaluated through the amount of litter produced. Resource quality was
      assessed by the mean content (percentage by weight) of N, C, S, and P of 30
      leaves from each shrub. The mean size of herbivores and their natural enemies
      were determined by measuring 20 adult specimens of each of the most abundant
      species. We found a higher species richness of soil microarthropods and foliar
      arthropods in the open site, although the diversity of foliage arthropods was
      lower in the closed site. Shrubs growing in the closed site tend to produce more,
      larger, and nutritionally poorer (lower nitrogen content) leaves than open site.
      Herbivores and their natural enemies were also larger in the closed site. We
      found a significant positive relationship between the diversity and species
      richness of foliar arthropods and the nitrogen content of leaves. In general,
      species richness and diversity of both the foliar and soil fauna, as well as the
      size of organisms belonging to higher trophic levels, were affected by vegetation
      cover and primary productivity at each site. These findings highlight the need to
      simultaneously consider at least four trophic levels (soil organisms, plants,
      herbivores, and natural enemies) to better understand the functioning of these
      systems and their responses to environmental changes. 

PMID- 25979000
TI  - Improving the care of patients with a hip fracture: a quality improvement report.
AB  - INTRODUCTION: Hip fractures are associated with high rates of morbidity and
      mortality and their incidence is set to increase. The National Hip Fracture
      Database and the Best Practice Tariff were introduced with the aim of improving
      patient care. This complete audit cycle charts the substantial clinical
      improvements that were achieved in a busy district general hospital. METHODS: The
      first audit cycle comprised 379 patients who were admitted between May 2012 and
      April 2013. The primary audit criterion was operative intervention within 36 h of
      admission. Variation according to the day of the week of admission was assessed
      to evaluate specific deficiencies in local service provision. The principle audit
      intervention was the introduction of two additional morning trauma lists. A re
      audit of 162 patients was conducted prospectively between January 2014 and June
      2014. RESULTS: Mean time to theatre was 49+/-39 h during the first audit cycle
      compared with 27+/-19 h (p<0.0001) during the second. Consequently, the
      proportion of patients undergoing operative intervention within 36 h of admission
      improved from 41% to 78% (p<0.0001). Overall achievement of Best Practice Tariff
      was significantly higher during the second cycle: 28% vs 73% (p<0.0001).
      CONCLUSIONS: Significant improvements in the quality of hip fracture care were
      achieved following this audit. These were accomplished by rigorously analysing
      the variation in Best Practice Tariff achievement according to the day of the
      week on which patients were admitted. Targeted interventions could therefore be
      introduced that addressed specific problems in local service provision.

PMID- 25979001
TI  - Crossing the quality chasm for Clostridium difficile infection prevention.

PMID- 25979004
TI  - Point/Counterpoint. Evaluation of treatment plans using target and normal tissue
      DVHs is no longer appropriate.

PMID- 25979003
TI  - Identification and Characterization of ProTx-III [MU-TRTX-Tp1a], a New Voltage
      Gated Sodium Channel Inhibitor from Venom of the Tarantula Thrixopelma pruriens.
AB  - Spider venoms are a rich source of ion channel modulators with therapeutic
      potential. Given the analgesic potential of subtype-selective inhibitors of
      voltage-gated sodium (NaV) channels, we screened spider venoms for inhibitors of
      human NaV1.7 (hNaV1.7) using a high-throughput fluorescent assay. Here, we
      describe the discovery of a novel NaV1.7 inhibitor, MU-TRTX-Tp1a (Tp1a), isolated
      from the venom of the Peruvian green-velvet tarantula Thrixopelma pruriens.
      Recombinant and synthetic forms of this 33-residue peptide preferentially
      inhibited hNaV1.7 > hNaV1.6 > hNaV1.2 > hNaV1.1 > hNaV1.3 channels in fluorescent
      assays. NaV1.7 inhibition was diminished (IC50 11.5 nM) and the association rate
      decreased for the C-terminal acid form of Tp1a compared with the native amidated
      form (IC50 2.1 nM), suggesting that the peptide C terminus contributes to its
      interaction with hNaV1.7. Tp1a had no effect on human voltage-gated calcium
      channels or nicotinic acetylcholine receptors at 5 MUM. Unlike most spider toxins
      that modulate NaV channels, Tp1a inhibited hNaV1.7 without significantly altering
      the voltage dependence of activation or inactivation. Tp1a proved to be analgesic
      by reversing spontaneous pain induced in mice by intraplantar injection in OD1, a
      scorpion toxin that potentiates hNaV1.7. The structure of Tp1a as determined
      using NMR spectroscopy revealed a classic inhibitor cystine knot (ICK) motif. The
      molecular surface of Tp1a presents a hydrophobic patch surrounded by positively
      charged residues, with subtle differences from other ICK spider toxins that might
      contribute to its different pharmacological profile. Tp1a may help guide the
      development of more selective and potent hNaV1.7 inhibitors for treatment of
      chronic pain. 

PMID- 25979002
TI  - Model Organisms in G Protein-Coupled Receptor Research.
AB  - The study of G protein-coupled receptors (GPCRs) has benefited greatly from
      experimental approaches that interrogate their functions in controlled,
      artificial environments. Working in vitro, GPCR receptorologists discovered the
      basic biologic mechanisms by which GPCRs operate, including their eponymous
      capacity to couple to G proteins; their molecular makeup, including the famed
      serpentine transmembrane unit; and ultimately, their three-dimensional structure.
      Although the insights gained from working outside the native environments of
      GPCRs have allowed for the collection of low-noise data, such approaches cannot
      directly address a receptor's native (in vivo) functions. An in vivo approach can
      complement the rigor of in vitro approaches: as studied in model organisms, it
      imposes physiologic constraints on receptor action and thus allows investigators
      to deduce the most salient features of receptor function. Here, we briefly
      discuss specific examples in which model organisms have successfully contributed
      to the elucidation of signals controlled through GPCRs and other surface receptor
      systems. We list recent examples that have served either in the initial discovery
      of GPCR signaling concepts or in their fuller definition. Furthermore, we
      selectively highlight experimental advantages, shortcomings, and tools of each
      model organism. 

PMID- 25979005
TI  - Reducing the effects of acoustic heterogeneity with an iterative reconstruction
      method from experimental data in microwave induced thermoacoustic tomography.
AB  - PURPOSE: An iterative reconstruction method has been previously reported by the
      authors of this paper. However, the iterative reconstruction method was
      demonstrated by solely using the numerical simulations. It is essential to apply
      the iterative reconstruction method to practice conditions. The objective of this
      work is to validate the capability of the iterative reconstruction method for
      reducing the effects of acoustic heterogeneity with the experimental data in
      microwave induced thermoacoustic tomography. METHODS: Most existing
      reconstruction methods need to combine the ultrasonic measurement technology to
      quantitatively measure the velocity distribution of heterogeneity, which
      increases the system complexity. Different to existing reconstruction methods,
      the iterative reconstruction method combines time reversal mirror technique, fast
      marching method, and simultaneous algebraic reconstruction technique to
      iteratively estimate the velocity distribution of heterogeneous tissue by solely
      using the measured data. Then, the estimated velocity distribution is used
      subsequently to reconstruct the highly accurate image of microwave absorption
      distribution. Experiments that a target placed in an acoustic heterogeneous
      environment are performed to validate the iterative reconstruction method.
      RESULTS: By using the estimated velocity distribution, the target in an acoustic
      heterogeneous environment can be reconstructed with better shape and higher image
      contrast than targets that are reconstructed with a homogeneous velocity
      distribution. CONCLUSIONS: The distortions caused by the acoustic heterogeneity
      can be efficiently corrected by utilizing the velocity distribution estimated by
      the iterative reconstruction method. The advantage of the iterative
      reconstruction method over the existing correction methods is that it is
      successful in improving the quality of the image of microwave absorption
      distribution without increasing the system complexity.

PMID- 25979006
TI  - Proton beam deflection in MRI fields: Implications for MRI-guided proton therapy.
AB  - PURPOSE: This paper investigates, via magnetic modeling and Monte Carlo
      simulation, the ability to deliver proton beams to the treatment zone inside a
      split-bore MRI-guided proton therapy system. METHODS: Field maps from a split
      bore 1 T MRI-Linac system are used as input to geant4 Monte Carlo simulations
      which model the trajectory of proton beams during their paths to the isocenter of
      the treatment area. Both inline (along the MRI bore) and perpendicular (through
      the split-bore gap) orientations are simulated. Monoenergetic parallel and
      diverging beams of energy 90, 195, and 300 MeV starting from 1.5 and 5 m above
      isocenter are modeled. A phase space file detailing a 2D calibration pattern is
      used to set the particle starting positions, and their spatial location as they
      cross isocenter is recorded. No beam scattering, collimation, or modulation of
      the proton beams is modeled. RESULTS: In the inline orientation, the radial
      symmetry of the solenoidal style fringe field acts to rotate the protons around
      the beam's central axis. For protons starting at 1.5 m from isocenter, this
      rotation is 19 degrees  (90 MeV) and 9.8 degrees  (300 MeV). A minor focusing
      toward the beam's central axis is also seen, but only significant, i.e., 2 mm
      shift at 150 mm off-axis, for 90 MeV protons. For the perpendicular orientation,
      the main MRI field and near fringe field act as the strongest to deflect the
      protons in a consistent direction. When starting from 1.5 m above isocenter
      shifts of 135 mm (90 MeV) and 65 mm (300 MeV) were observed. Further to this, off
      axis protons are slightly deflected toward or away from the central axis in the
      direction perpendicular to the main deflection direction. This leads to a
      distortion of the phase space pattern, not just a shift. This distortion
      increases from zero at the central axis to 10 mm (90 MeV) and 5 mm (300 MeV) for
      a proton 150 mm off-axis. In both orientations, there is a small but subtle
      difference in the deflection and distortion pattern between protons fired
      parallel to the beam axis and those fired from a point source. This is indicative
      of the 3D spatially variant nature of the MRI fringe field. CONCLUSIONS: For the
      first time, accurate magnetic and Monte Carlo modeling have been used to assess
      the transport of generic proton beams toward a 1 T split-bore MRI. Significant
      rotation is observed in the inline orientation, while more complex deflection and
      distortion are seen in the perpendicular orientation. The results of this study
      suggest that due to the complexity and energy-dependent nature of the magnetic
      deflection and distortion, the pencil beam scanning method will be the only
      choice for delivering a therapeutic proton beam inside a potential MRI-guided
      proton therapy system in either the inline or perpendicular orientation. Further
      to this, significant correction strategies will be required to account for the
      MRI fringe fields.

PMID- 25979007
TI  - Optimization of leaf margins for lung stereotactic body radiotherapy using a
      flattening filter-free beam.
AB  - PURPOSE: The authors sought to determine the optimal collimator leaf margins
      which minimize normal tissue dose while achieving high conformity and to evaluate
      differences between the use of a flattening filter-free (FFF) beam and a
      flattening-filtered (FF) beam. METHODS: Sixteen lung cancer patients scheduled
      for stereotactic body radiotherapy underwent treatment planning for a 7 MV FFF
      and a 6 MV FF beams to the planning target volume (PTV) with a range of leaf
      margins (-3 to 3 mm). Forty grays per four fractions were prescribed as a PTV
      D95. For PTV, the heterogeneity index (HI), conformity index, modified gradient
      index (GI), defined as the 50% isodose volume divided by target volume, maximum
      dose (Dmax), and mean dose (D mean) were calculated. Mean lung dose (MLD), V20
      Gy, and V5 Gy for the lung (defined as the volumes of lung receiving at least 20
      and 5 Gy), mean heart dose, and Dmax to the spinal cord were measured as doses to
      organs at risk (OARs). Paired t-tests were used for statistical analysis.
      RESULTS: HI was inversely related to changes in leaf margin. Conformity index and
      modified GI initially decreased as leaf margin width increased. After reaching a
      minimum, the two values then increased as leaf margin increased ("V" shape). The
      optimal leaf margins for conformity index and modified GI were -1.1 +/- 0.3 mm
      (mean +/- 1 SD) and -0.2 +/- 0.9 mm, respectively, for 7 MV FFF compared to -1.0
      +/- 0.4 and -0.3 +/- 0.9 mm, respectively, for 6 MV FF. Dmax and D mean for 7 MV
      FFF were higher than those for 6 MV FF by 3.6% and 1.7%, respectively. There was
      a positive correlation between the ratios of HI, Dmax, and D mean for 7 MV FFF to
      those for 6 MV FF and PTV size (R = 0.767, 0.809, and 0.643, respectively). The
      differences in MLD, V20 Gy, and V5 Gy for lung between FFF and FF beams were
      negligible. The optimal leaf margins for MLD, V20 Gy, and V5 Gy for lung were 
      0.9 +/- 0.6, -1.1 +/- 0.8, and -2.1 +/- 1.2 mm, respectively, for 7 MV FFF
      compared to -0.9 +/- 0.6, -1.1 +/- 0.8, and -2.2 +/- 1.3 mm, respectively, for 6
      MV FF. With the heart inside the radiation field, the mean heart dose showed a V
      shaped relationship with leaf margins. The optimal leaf margins were -1.0 +/- 0.6
      mm for both beams. Dmax to the spinal cord showed no clear trend for changes in
      leaf margin. CONCLUSIONS: The differences in doses to OARs between FFF and FF
      beams were negligible. Conformity index, modified GI, MLD, lung V20 Gy, lung V5
      Gy, and mean heart dose showed a V-shaped relationship with leaf margins. There
      were no significant differences in optimal leaf margins to minimize these
      parameters between both FFF and FF beams. The authors' results suggest that a
      leaf margin of -1 mm achieves high conformity and minimizes doses to OARs for
      both FFF and FF beams.

PMID- 25979008
TI  - Dosimetric characterization of two radium sources for retrospective dosimetry
      studies.
AB  - PURPOSE: During the first part of the 20th century, (226)Ra was the most used
      radionuclide for brachytherapy. Retrospective accurate dosimetry, coupled with
      patient follow up, is important for advancing knowledge on long-term radiation
      effects. The purpose of this work was to dosimetrically characterize two (226)Ra
      sources, commonly used in Sweden during the first half of the 20th century, for
      retrospective dose-effect studies. METHODS: An 8 mg (226)Ra tube and a 10 mg
      (226)Ra needle, used at Radiumhemmet (Karolinska University Hospital, Stockholm,
      Sweden), from 1925 to the 1960s, were modeled in two independent Monte Carlo (MC)
      radiation transport codes: geant4 and mcnp5. Absorbed dose and collision kerma
      around the two sources were obtained, from which the TG-43 parameters were
      derived for the secular equilibrium state. Furthermore, results from this
      dosimetric formalism were compared with results from a MC simulation with a
      superficial mould constituted by five needles inside a glass casing, placed over
      a water phantom, trying to mimic a typical clinical setup. Calculated absorbed
      doses using the TG-43 formalism were also compared with previously reported
      measurements and calculations based on the Sievert integral. Finally, the dose
      rate at large distances from a (226)Ra point-like-source placed in the center of
      1 m radius water sphere was calculated with geant4. RESULTS: TG-43 parameters
      [including gL(r), F(r, theta), Lambda, and sK] have been uploaded in spreadsheets
      as additional material, and the fitting parameters of a mathematical curve that
      provides the dose rate between 10 and 60 cm from the source have been provided.
      Results from TG-43 formalism are consistent within the treatment volume with
      those of a MC simulation of a typical clinical scenario. Comparisons with
      reported measurements made with thermoluminescent dosimeters show differences up
      to 13% along the transverse axis of the radium needle. It has been estimated that
      the uncertainty associated to the absorbed dose within the treatment volume is
      10%-15%, whereas uncertainty of absorbed dose to distant organs is roughly 20%
      25%. CONCLUSIONS: The results provided here facilitate retrospective dosimetry
      studies of (226)Ra using modern treatment planning systems, which may be used to
      improve knowledge on long term radiation effects. It is surely important for the
      epidemiologic studies to be aware of the estimated uncertainty provided here
      before extracting their conclusions.

PMID- 25979009
TI  - Noninvasive hemodynamic assessment, treatment outcome prediction and follow-up of
      aortic coarctation from MR imaging.
AB  - PURPOSE: Coarctation of the aorta (CoA) is a congenital heart disease
      characterized by an abnormal narrowing of the proximal descending aorta. Severity
      of this pathology is quantified by the blood pressure drop (?P) across the
      stenotic coarctation lesion. In order to evaluate the physiological significance
      of the preoperative coarctation and to assess the postoperative results, the
      hemodynamic analysis is routinely performed by measuring the ?P across the
      coarctation site via invasive cardiac catheterization. The focus of this work is
      to present an alternative, noninvasive measurement of blood pressure drop ?P
      through the introduction of a fast, image-based workflow for personalized
      computational modeling of the CoA hemodynamics. METHODS: The authors propose an
      end-to-end system comprised of shape and computational models, their
      personalization setup using MR imaging, and a fast, noninvasive method based on
      computational fluid dynamics (CFD) to estimate the pre- and postoperative
      hemodynamics for coarctation patients. A virtual treatment method is investigated
      to assess the predictive power of our approach. RESULTS: Automatic thoracic aorta
      segmentation was applied on a population of 212 3D MR volumes, with mean
      symmetric point-to-mesh error of 3.00 +/- 1.58 mm and average computation time of
      8 s. Through quantitative evaluation of 6 CoA patients, good agreement between
      computed blood pressure drop and catheter measurements is shown: average
      differences are 2.38 +/- 0.82 mm Hg (pre-), 1.10 +/- 0.63 mm Hg (postoperative),
      and 4.99 +/- 3.00 mm Hg (virtual stenting), respectively. CONCLUSIONS: The
      complete workflow is realized in a fast, mostly-automated system that is
      integrable in the clinical setting. To the best of our knowledge, this is the
      first time that three different settings (preoperative--severity assessment,
      poststenting--follow-up, and virtual stenting--treatment outcome prediction) of
      CoA are investigated on multiple subjects. We believe that in future-given wider
      clinical validation-our noninvasive in-silico method could replace invasive
      pressure catheterization for CoA.

PMID- 25979010
TI  - Noncoplanar VMAT for nasopharyngeal tumors: Plan quality versus treatment time.
AB  - PURPOSE: The authors investigated the potential of optimized noncoplanar
      irradiation trajectories for volumetric modulated arc therapy (VMAT) treatments
      of nasopharyngeal patients and studied the trade-off between treatment plan
      quality and delivery time in radiation therapy. METHODS: For three nasopharyngeal
      patients, the authors generated treatment plans for nine different delivery
      scenarios using dedicated optimization methods. They compared these scenarios
      according to dose characteristics, number of beam directions, and estimated
      delivery times. In particular, the authors generated the following treatment
      plans: (1) a 4pi plan, which is a not sequenced, fluence optimized plan that uses
      beam directions from approximately 1400 noncoplanar directions and marks a
      theoretical upper limit of the treatment plan quality, (2) a coplanar 2pi plan
      with 72 coplanar beam directions as pendant to the noncoplanar 4pi plan, (3) a
      coplanar VMAT plan, (4) a coplanar step and shoot (SnS) plan, (5) a beam angle
      optimized (BAO) coplanar SnS IMRT plan, (6) a noncoplanar BAO SnS plan, (7) a
      VMAT plan with rotated treatment couch, (8) a noncoplanar VMAT plan with an
      optimized great circle around the patient, and (9) a noncoplanar BAO VMAT plan
      with an arbitrary trajectory around the patient. RESULTS: VMAT using optimized
      noncoplanar irradiation trajectories reduced the mean and maximum doses in organs
      at risk compared to coplanar VMAT plans by 19% on average while the target
      coverage remains constant. A coplanar BAO SnS plan was superior to coplanar SnS
      or VMAT; however, noncoplanar plans like a noncoplanar BAO SnS plan or
      noncoplanar VMAT yielded a better plan quality than the best coplanar 2pi plan.
      The treatment plan quality of VMAT plans depended on the length of the
      trajectory. The delivery times of noncoplanar VMAT plans were estimated to be 6.5
      min in average; 1.6 min longer than a coplanar plan but on average 2.8 min faster
      than a noncoplanar SnS plan with comparable treatment plan quality. CONCLUSIONS:
      The authors' study reconfirms the dosimetric benefits of noncoplanar irradiation
      of nasopharyngeal tumors. Both SnS using optimized noncoplanar beam ensembles and
      VMAT using an optimized, arbitrary, noncoplanar trajectory enabled dose
      reductions in organs at risk compared to coplanar SnS and VMAT. Using great
      circles or simple couch rotations to implement noncoplanar VMAT, however, was not
      sufficient to yield meaningful improvements in treatment plan quality. The
      authors estimate that noncoplanar VMAT using arbitrary optimized irradiation
      trajectories comes at an increased delivery time compared to coplanar VMAT yet at
      a decreased delivery time compared to noncoplanar SnS IMRT.

PMID- 25979011
TI  - An adaptive filtered back-projection for photoacoustic image reconstruction.
AB  - PURPOSE: The purpose of this study is to develop an improved filtered-back
      projection (FBP) algorithm for photoacoustic tomography (PAT), which allows image
      reconstruction with higher quality compared to images reconstructed through
      traditional algorithms. METHODS: A rigorous expression of a weighting function
      has been derived directly from a photoacoustic wave equation and used as a ramp
      filter in Fourier domain. The authors' new algorithm utilizes this weighting
      function to precisely calculate each photoacoustic signal's contribution and then
      reconstructs the image based on the retarded potential generated from the
      photoacoustic sources. In addition, an adaptive criterion has been derived for
      selecting the cutoff frequency of a low pass filter. Two computational phantoms
      were created to test the algorithm. The first phantom contained five spheres with
      each sphere having different absorbances. The phantom was used to test the
      capability for correctly representing both the geometry and the relative absorbed
      energy in a planar measurement system. The authors also used another phantom
      containing absorbers of different sizes with overlapping geometry to evaluate the
      performance of the new method for complicated geometry. In addition, random noise
      background was added to the simulated data, which were obtained by using an arc
      shaped array of 50 evenly distributed transducers that spanned 160 degrees  over
      a circle with a radius of 65 mm. A normalized factor between the neighbored
      transducers was applied for correcting measurement signals in PAT simulations.
      The authors assumed that the scanned object was mounted on a holder that rotated
      over the full 360 degrees  and the scans were set to a sampling rate of 20.48
      MHz. RESULTS: The authors have obtained reconstructed images of the computerized
      phantoms by utilizing the new FBP algorithm. From the reconstructed image of the
      first phantom, one can see that this new approach allows not only obtaining a
      sharp image but also showing the correct signal strength of the absorbers. The
      reconstructed image of the second phantom further demonstrates the capability to
      form clear images of the spheres with sharp borders in the overlapping geometry.
      The smallest sphere is clearly visible and distinguishable, even though it is
      surrounded by two big spheres. In addition, image reconstructions were conducted
      with randomized noise added to the observed signals to mimic realistic
      experimental conditions. CONCLUSIONS: The authors have developed a new FBP
      algorithm that is capable for reconstructing high quality images with correct
      relative intensities and sharp borders for PAT. The results demonstrate that the
      weighting function serves as a precise ramp filter for processing the observed
      signals in the Fourier domain. In addition, this algorithm allows an adaptive
      determination of the cutoff frequency for the applied low pass filter.

PMID- 25979012
TI  - An extension to artifact-free projection overlaps.
AB  - PURPOSE: In multipinhole single photon emission computed tomography, the
      overlapping of projections has been used to increase sensitivity. Avoiding
      artifacts in the reconstructed image associated with projection overlaps
      (multiplexing) is a critical issue. In our previous report, two types of artifact
      free projection overlaps, i.e., projection overlaps that do not lead to artifacts
      in the reconstructed image, were formally defined and proved, and were validated
      via simulations. In this work, a new proposition is introduced to extend the
      previously defined type-II artifact-free projection overlaps so that a broader
      range of artifact-free overlaps is accommodated. One practical purpose of the new
      extension is to design a baffle window multipinhole system with artifact-free
      projection overlaps. METHODS: First, the extended type-II artifact-free overlap
      was theoretically defined and proved. The new proposition accommodates the
      situation where the extended type-II artifact-free projection overlaps can be
      produced with incorrectly reconstructed portions in the reconstructed image.
      Next, to validate the theory, the extended-type-II artifact-free overlaps were
      employed in designing the multiplexing multipinhole spiral orbit imaging systems
      with a baffle window. Numerical validations were performed via simulations, where
      the corresponding 1-pinhole nonmultiplexing reconstruction results were used as
      the benchmark for artifact-free reconstructions. The mean square error (MSE) was
      the metric used for comparisons of noise-free reconstructed images. Noisy
      reconstructions were also performed as part of the validations. RESULTS:
      Simulation results show that for noise-free reconstructions, the MSEs of the
      reconstructed images of the artifact-free multiplexing systems are very similar
      to those of the corresponding 1-pinhole systems. No artifacts were observed in
      the reconstructed images. Therefore, the testing results for artifact-free
      multiplexing systems designed using the extended type-II artifact-free overlaps
      numerically validated the developed theory. CONCLUSIONS: First, the extension
      itself is of theoretical importance because it broadens the selection range for
      optimizing multiplexing multipinhole designs. Second, the extension has an
      immediate application: using a baffle window to design a special spiral orbit
      multipinhole imaging system with projection overlaps in the orbit axial
      direction. Such an artifact-free baffle window design makes it possible for us to
      image any axial portion of interest of a long object with projection overlaps to
      increase sensitivity.

PMID- 25979013
TI  - Optical eye tracking system for real-time noninvasive tumor localization in
      external beam radiotherapy.
AB  - PURPOSE: External beam radiotherapy currently represents an important therapeutic
      strategy for the treatment of intraocular tumors. Accurate target localization
      and efficient compensation of involuntary eye movements are crucial to avoid
      deviations in dose distribution with respect to the treatment plan. This paper
      describes an eye tracking system (ETS) based on noninvasive infrared video
      imaging. The system was designed for capturing the tridimensional (3D) ocular
      motion and provides an on-line estimation of intraocular lesions position based
      on a priori knowledge coming from volumetric imaging. METHODS: Eye tracking is
      performed by localizing cornea and pupil centers on stereo images captured by two
      calibrated video cameras, exploiting eye reflections produced by infrared
      illumination. Additionally, torsional eye movements are detected by template
      matching in the iris region of eye images. This information allows estimating the
      3D position and orientation of the eye by means of an eye local reference system.
      By combining ETS measurements with volumetric imaging for treatment planning
      [computed tomography (CT) and magnetic resonance (MR)], one is able to map the
      position of the lesion to be treated in local eye coordinates, thus enabling real
      time tumor referencing during treatment setup and irradiation. Experimental tests
      on an eye phantom and seven healthy subjects were performed to assess ETS
      tracking accuracy. RESULTS: Measurements on phantom showed an overall median
      accuracy within 0.16 mm and 0.40 degrees  for translations and rotations,
      respectively. Torsional movements were affected by 0.28 degrees  median
      uncertainty. On healthy subjects, the gaze direction error ranged between 0.19
      degrees  and 0.82 degrees  at a median working distance of 29 cm. The median
      processing time of the eye tracking algorithm was 18.60 ms, thus allowing eye
      monitoring up to 50 Hz. CONCLUSIONS: A noninvasive ETS prototype was designed to
      perform real-time target localization and eye movement monitoring during ocular
      radiotherapy treatments. The device aims at improving state-of-the-art invasive
      procedures based on surgical implantation of radiopaque clips and repeated
      acquisition of X-ray images, with expected positive effects on treatment quality
      and patient outcome.

PMID- 25979014
TI  - Novel magnetic heating probe for multimodal cancer treatment.
AB  - PURPOSE: Multifunctional materials consisting of polymers and magnetic
      nanoparticles (MNPs) are highly sought after in the field of biomedical
      engineering. These materials offer new opportunities for the development of novel
      cancer treatment modalities that can increase the efficacy of cancer therapy. In
      this paper, a novel probe for multimodal cancer treatment is proposed and
      analyzed. The probe is essentially a cannula with two main parts: a distal heat
      generating tip made of a magnetic nanocomposite and a proximal insulated shaft.
      METHODS: A description of the concept and functional operations of the probe is
      presented. In an effort to assess its feasibility, the authors evaluated the
      ability of probe tip (made of PMMA-Fe3O4 nanocomposite) to generate heat in
      biological tissue using alternating magnetic field (AMF) parameters (field
      strength and frequency) that are acceptable for human use. Heat generation by
      MNPs was determined using the linear response theory. The effects of Fe3O4 volume
      fraction on heat generation as well as treatment time on the thermal dose were
      studied. The finite element method model was tested for its validity using an
      analytical model. RESULTS: Lesions were revealed to have an ellipsoidal shape and
      their sizes were affected by treatment time. However, their shapes remained
      unchanged. The comparison with the analytical model showed reasonably a good
      agreement to within 2%. Furthermore, the authors' numerical predictions also
      showed reasonable agreement with the experimental results previously reported in
      the literature. CONCLUSIONS: The authors' predictions demonstrate the feasibility
      of their novel probe to achieve reasonable lesion sizes, during hyperthermic or
      ablative heating using AMF parameters (field strength and frequency) that are
      acceptable for human use.

PMID- 25979015
TI  - Robust optimization methods for cardiac sparing in tangential breast IMRT.
AB  - PURPOSE: In left-sided tangential breast intensity modulated radiation therapy
      (IMRT), the heart may enter the radiation field and receive excessive radiation
      while the patient is breathing. The patient's breathing pattern is often
      irregular and unpredictable. We verify the clinical applicability of a heart
      sparing robust optimization approach for breast IMRT. We compare robust optimized
      plans with clinical plans at free-breathing and clinical plans at deep
      inspiration breath-hold (DIBH) using active breathing control (ABC). METHODS:
      Eight patients were included in the study with each patient simulated using 4D
      CT. The 4D-CT image acquisition generated ten breathing phase datasets. An
      average scan was constructed using all the phase datasets. Two of the eight
      patients were also imaged at breath-hold using ABC. The 4D-CT datasets were used
      to calculate the accumulated dose for robust optimized and clinical plans based
      on deformable registration. We generated a set of simulated breathing probability
      mass functions, which represent the fraction of time patients spend in different
      breathing phases. The robust optimization method was applied to each patient
      using a set of dose-influence matrices extracted from the 4D-CT data and a model
      of the breathing motion uncertainty. The goal of the optimization models was to
      minimize the dose to the heart while ensuring dose constraints on the target were
      achieved under breathing motion uncertainty. RESULTS: Robust optimized plans were
      improved or equivalent to the clinical plans in terms of heart sparing for all
      patients studied. The robust method reduced the accumulated heart dose (D10cc) by
      up to 801 cGy compared to the clinical method while also improving the coverage
      of the accumulated whole breast target volume. On average, the robust method
      reduced the heart dose (D10cc) by 364 cGy and improved the optBreast dose (D99%)
      by 477 cGy. In addition, the robust method had smaller deviations from the
      planned dose to the accumulated dose. The deviation of the accumulated dose from
      the planned dose for the optBreast (D99%) was 12 cGy for robust versus 445 cGy
      for clinical. The deviation for the heart (D10cc) was 41 cGy for robust and 320
      cGy for clinical. CONCLUSIONS: The robust optimization approach can reduce heart
      dose compared to the clinical method at free-breathing and can potentially reduce
      the need for breath-hold techniques.

PMID- 25979016
TI  - Ultrashort echo-time MRI versus CT for skull aberration correction in MR-guided
      transcranial focused ultrasound: In vitro comparison on human calvaria.
AB  - PURPOSE: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS)
      brain treatment systems compensate for skull-induced beam aberrations by
      adjusting the phase and amplitude of individual ultrasound transducer elements.
      These corrections are currently calculated based on a preacquired computed
      tomography (CT) scan of the patient's head. The purpose of the work presented
      here is to demonstrate the feasibility of using ultrashort echo-time magnetic
      resonance imaging (UTE MRI) instead of CT to calculate and apply aberration
      corrections on a clinical TcMRgFUS system. METHODS: Phantom experiments were
      performed in three ex-vivo human skulls filled with tissue-mimicking hydrogel.
      Each skull phantom was imaged with both CT and UTE MRI. The MR images were then
      segmented into "skull" and "not-skull" pixels using a computationally efficient,
      threshold-based algorithm, and the resulting 3D binary skull map was converted
      into a series of 2D virtual CT images. Each skull was mounted in the head
      transducer of a clinical TcMRgFUS system (ExAblate Neuro, Insightec, Israel), and
      transcranial sonications were performed using a power setting of approximately
      750 acoustic watts at several different target locations within the electronic
      steering range of the transducer. Each target location was sonicated three times:
      once using aberration corrections calculated from the actual CT scan, once using
      corrections calculated from the MRI-derived virtual CT scan, and once without
      applying any aberration correction. MR thermometry was performed in conjunction
      with each 10-s sonication, and the highest single-pixel temperature rise and
      surrounding-pixel mean were recorded for each sonication. RESULTS: The measured
      temperature rises were ~ 45% larger for aberration-corrected sonications than for
      noncorrected sonications. This improvement was highly significant (p < 10(-4)).
      The difference between the single-pixel peak temperature rise and the surrounding
      pixel mean, which reflects the sharpness of the thermal focus, was also
      significantly larger for aberration-corrected sonications. There was no
      significant difference between the sonication results achieved using CT-based and
      MR-based aberration correction. CONCLUSIONS: The authors have demonstrated that
      transcranial focal heating can be significantly improved in vitro by using UTE
      MRI to compute skull-induced ultrasound aberration corrections. Their results
      suggest that UTE MRI could be used instead of CT to implement such corrections on
      current 0.7 MHz clinical TcMRgFUS devices. The MR image acquisition and
      segmentation procedure demonstrated here would add less than 15 min to a clinical
      MRgFUS treatment session.

PMID- 25979017
TI  - The emergence of nonuniform spatiotemporal fractionation schemes within the
      standard BED model.
AB  - PURPOSE: Nonuniform spatiotemporal radiotherapy fractionation schemes, i.e.,
      delivering distinct dose distributions in different fractions can potentially
      improve the therapeutic ratio. This is possible if the dose distributions are
      designed such that similar doses are delivered to normal tissues (exploit the
      fractionation effect) while hypofractionating subregions of the tumor. In this
      paper, the authors develop methodology for treatment planning with nonuniform
      fractions and demonstrate this concept in the context of intensity-modulated
      proton therapy (IMPT). METHODS: Treatment planning is performed by simultaneously
      optimizing (possibly distinct) IMPT dose distributions for multiple fractions.
      This is achieved using objective and constraint functions evaluated for the
      cumulative biologically equivalent dose (BED) delivered at the end of treatment.
      BED based treatment planning formulations lead to nonconvex optimization
      problems, such that local gradient based algorithms require adequate starting
      positions to find good local optima. To that end, the authors develop a
      combinatorial algorithm to initialize the pencil beam intensities. RESULTS: The
      concept of nonuniform spatiotemporal fractionation schemes is demonstrated for a
      spinal metastasis patient treated in two fractions using stereotactic body
      radiation therapy. The patient is treated with posterior oblique beams with the
      kidneys being located in the entrance region of the beam. It is shown that a
      nonuniform fractionation scheme that hypofractionates the central part of the
      tumor allows for a skin and kidney BED reduction of approximately 10%-20%.
      CONCLUSIONS: Nonuniform spatiotemporal fractionation schemes represent a novel
      approach to exploit fractionation effects that deserves further exploration for
      selected disease sites.

PMID- 25979018
TI  - Effectiveness of digital infrared thermal imaging in detecting lower extremity
      deep venous thrombosis.
AB  - PURPOSE: The authors aimed to determine the effectiveness of infrared thermal
      imaging (IRTI) as a novel, noninvasive technique in adjunctive diagnostic
      screening for lower limb deep venous thrombosis (DVT). METHODS: The authors used
      an infrared thermal imaging sensor to examine the lower limbs of 64 DVT patients
      and 64 healthy volunteers. The DVT patients had been definitively diagnosed with
      either Doppler vascular compression ultrasonography or angiography. The mean area
      temperature (T_area) and mean linear temperature (T_line) in the region of
      interest were determined with infrared thermal imaging. Images were evaluated
      with qualitative pseudocolor analysis to verify specific color-temperature
      responses and with quantitative temperature analysis. Differences in T_area and
      T_line between the DVT limb and the nonaffected limb in each DVT patient and
      temperature differences (TDs) in T_area (TDarea) and T_line (TDline) between DVT
      patients and non-DVT volunteers were compared. RESULTS: Qualitative pseudocolor
      analysis revealed visible asymmetry between the DVT side and non-DVT side in the
      presentation and distribution characteristics (PDCs) of infrared thermal images.
      The DVT limbs had areas of abnormally high temperature, indicating the presence
      of DVT. Of the 64 confirmed DVT patients, 62 (96.88%) were positive by IRTI
      detection. Among these 62 IRTI-positive cases, 53 (82.81%) showed PDCs that
      agreed with the DVT regions detected by Doppler vascular compression
      ultrasonography or angiography. In nine patients (14.06%), IRTI PDCs did not
      definitively agree with the DVT regions established with other testing methods,
      but still correctly indicated the DVT-affected limb. There was a highly
      significant difference between DVT and non-DVT sides in DVT patients (P < 0.01).
      The TDarea and TDline in non-DVT volunteers ranged from 0.19 +/- 0.15  degrees C
      to 0.21  degrees C +/- 0.17  degrees C; those in DVT patients ranged from 0.86 
      degrees C +/- 0.71  degrees C to 1.03  degrees C +/- 0.79  degrees C (P < 0.01).
      CONCLUSIONS: Infrared thermal imaging can be effectively used in DVT detection
      and adjunctive diagnostic screening because of its specific infrared PDCs and TDs
      values.

PMID- 25979019
TI  - Simultaneous segmentation and iterative registration method for computing ADC
      with reduced artifacts from DW-MRI.
AB  - PURPOSE: Apparent diffusion coefficient (ADC), derived from diffusion-weighted
      magnetic resonance images (DW-MRI), measures the motion of water molecules in
      vivo and can be used to quantify tumor response to therapy. The accurate
      measurement of ADC can be adversely affected by organ motion and imaging
      artifacts. In this paper, the authors' goal was to develop an automated method
      for reducing artifacts and thereby improve the accuracy of ADC measurements in
      moving organs such as liver. METHODS: The authors developed a novel method of
      computing ADC with fewer artifacts, through simultaneous image segmentation and
      iterative registration (SSIR) of multiple b-value DW-MRI. The authors' approach
      reduces artifacts by automatically finding the best possible alignment between
      the individual b-value images and a reference DW image using a sequence of
      transformations. It selects such a sequence by an iterative choice of b-value DW
      images based on the accuracy of their alignment with the reference DW image. The
      authors' approach quantifies the accuracy of alignment between a pair of images
      using modified Hausdroff distance computed between the structures of interest.
      The structures of interest are identified by a user through strokes drawn in one
      or more slices in the reference DW image, which are then volumetrically segmented
      using GrowCut. The same structures are segmented in the remaining b-value images
      by transforming the user-drawn strokes through registration. The ADC values are
      computed from all the aligned b-value images. The images are aligned by using
      affine registration followed by deformable B-spline registration with cubic B
      spline resampling. RESULTS: The authors compared the results of ADC computed
      using their approach with ADC computed (a) without registration and (b) with
      basic affine registration of all b-value images to a chosen reference. The
      authors' approach was the most effective in reducing artifacts compared to the
      other two methods. It resulted in a mean artifact ratio (fraction of voxels in a
      structure with negative ADC over total number of voxels in the structure) of 2.7%
      versus 5.4% for affine registration and 32% for no registration for >200 tumors.
      The authors' approach also resulted in the lowest median standard deviation in
      the computed mean ADC for all tumors [0.05,0.09,0.07,0.58] compared to those from
      affine image registration [0.02, 0.14, 0.58, 0.79] and no image registration
      [0.64, 0.83, 0.83, 1.09] on tests where random displacement [8,10,12,16] pixels
      were introduced in multiple trials in the b-value images. CONCLUSIONS: The
      authors developed a novel approach for reducing artifacts in ADC maps through
      simultaneous registration and segmentation of multiple b-value DW images. The
      authors' method explicitly employs a registration quality metric to align images.
      When compared to basic affine and no image registrations, the authors' approach
      produces registrations of greater accuracy with lowest artifact ratio and median
      standard deviation of the computed mean ADC values for a wide range of
      displacements.

PMID- 25979020
TI  - Technical Note: Measuring contrast- and noise-dependent spatial resolution of an
      iterative reconstruction method in CT using ensemble averaging.
AB  - PURPOSE: The spatial resolution of iterative reconstruction (IR) in computed
      tomography (CT) is contrast- and noise-dependent because of the nonlinear
      regularization. Due to the severe noise contamination, it is challenging to
      perform precise spatial-resolution measurements at very low-contrast levels. The
      purpose of this study was to measure the spatial resolution of a commercially
      available IR method using ensemble-averaged images acquired from repeated scans.
      METHODS: A low-contrast phantom containing three rods (7, 14, and 21 HU below
      background) was scanned on a 128-slice CT scanner at three dose levels (CTDIvol =
      16, 8, and 4 mGy). Images were reconstructed using two filtered-backprojection
      (FBP) kernels (B40 and B20) and a commercial IR method (sinogram affirmed
      iterative reconstruction, SAFIRE, Siemens Healthcare) with two strength settings
      (I40-3 and I40-5). The same scan was repeated 100 times at each dose level. The
      modulation transfer function (MTF) was calculated based on the edge profile
      measured on the ensemble-averaged images. RESULTS: The spatial resolution of the
      two FBP kernels, B40 and B20, remained relatively constant across contrast and
      dose levels. However, the spatial resolution of the two IR kernels degraded
      relative to FBP as contrast or dose level decreased. For a given dose level at 16
      mGy, the MTF50% value normalized to the B40 kernel decreased from 98.4% at 21 HU
      to 88.5% at 7 HU for I40-3 and from 97.6% to 82.1% for I40-5. At 21 HU, the
      relative MTF50% value decreased from 98.4% at 16 mGy to 90.7% at 4 mGy for I40-3
      and from 97.6% to 85.6% for I40-5. CONCLUSIONS: A simple technique using ensemble
      averaging from repeated CT scans can be used to measure the spatial resolution of
      IR techniques in CT at very low contrast levels. The evaluated IR method degraded
      the spatial resolution at low contrast and high noise levels.

PMID- 25979022
TI  - A dual-Kinect approach to determine torso surface motion for respiratory motion
      correction in PET.
AB  - PURPOSE: Respiratory gating is commonly used to reduce blurring effects and
      attenuation correction artifacts in positron emission tomography (PET).
      Established clinically available methods that employ body-attached hardware for
      acquiring respiration signals rely on the assumption that external surface motion
      and internal organ motion are well correlated. In this paper, the authors present
      a markerless method comprising two Microsoft Kinects for determining the motion
      on the whole torso surface and aim to demonstrate its validity and usefulness
      including the potential to study the external/internal correlation and to provide
      useful information for more advanced correction approaches. METHODS: The data of
      two Kinects are used to calculate 3D representations of a patient's torso surface
      with high spatial coverage. Motion signals can be obtained for any position by
      tracking the mean distance to a virtual camera with a view perpendicular to the
      surrounding surface. The authors have conducted validation experiments including
      volunteers and a moving high-precision platform to verify the method's
      suitability for providing meaningful data. In addition, the authors employed it
      during clinical (18)F-FDG-PET scans and exemplarily analyzed the acquired data of
      ten cancer patients. External signals of abdominal and thoracic regions as well
      as data-driven signals were used for gating and compared with respect to detected
      displacement of present lesions. Additionally, the authors quantified signal
      similarities and time shifts by analyzing cross-correlation sequences. RESULTS:
      The authors' results suggest a Kinect depth resolution of approximately 1 mm at
      75 cm distance. Accordingly, valid signals could be obtained for surface
      movements with small amplitudes in the range of only few millimeters. In this
      small sample of ten patients, the abdominal signals were better suited for gating
      the PET data than the thoracic signals and the correlation of data-driven signals
      was found to be stronger with abdominal signals than with thoracic signals
      (average Pearson correlation coefficients of 0.74 +/- 0.17 and 0.45 +/- 0.23,
      respectively). In all cases, except one, the abdominal respiratory motion
      preceded the thoracic motion-a maximum delay of approximately 600 ms was
      detected. CONCLUSIONS: The method provides motion information with sufficiently
      high spatial and temporal resolution. Thus, it enables meaningful analysis in the
      form of comparisons between amplitudes and phase shifts of signals from different
      regions. In combination with a large field-of-view, as given by combining the
      data of two Kinect cameras, it yields surface representations that might be
      useful in the context of motion correction and motion modeling.

PMID- 25979021
TI  - Impact of positional difference on the measurement of breast density using MRI.
AB  - PURPOSE: This study investigated the impact of arms/hands and body position on
      the measurement of breast density using MRI. METHODS: Noncontrast-enhanced T1
      weighted images were acquired from 32 healthy women. Each subject received four
      MR scans using different experimental settings, including a high resolution hands
      up, a low resolution hands-up, a high resolution hands-down, and finally, another
      high resolution hands-up after repositioning. The breast segmentation was
      performed using a fully automatic chest template-based method. The breast volume
      (BV), fibroglandular tissue volume (FV), and percent density (PD) measured from
      the four MR scan settings were analyzed. RESULTS: A high correlation of BV, FV,
      and PD between any pair of the four MR scans was noted (r > 0.98 for all). Using
      the generalized estimating equation method, a statistically significant
      difference in mean BV among four settings was noted (left breast, score test p =
      0.0056; right breast, score test p = 0.0016), adjusted for age and body mass
      index. Despite differences in BV, there were no statistically significant
      differences in the mean PDs among the four settings (p > 0.10 for left and right
      breasts). Using Bland-Altman plots, the smallest mean difference/bias and
      standard deviations for BV, FV, and PD were noted when comparing hands-up high vs
      low resolution when the breast positions were exactly the same. CONCLUSIONS: The
      authors' study showed that BV, FV, and PD measurements from MRI of different
      positions were highly correlated. BV may vary with positions but the measured PD
      did not differ significantly between positions. The study suggested that the
      percent density analyzed from MRI studies acquired using different arms/hands and
      body positions from multiple centers can be combined for analysis.

PMID- 25979023
TI  - Cyst-based measurements for assessing lymphangioleiomyomatosis in computed
      tomography.
AB  - PURPOSE: To investigate the efficacy of a new family of measurements made on
      individual pulmonary cysts extracted from computed tomography (CT) for assessing
      the severity of lymphangioleiomyomatosis (LAM). METHODS: CT images were analyzed
      using thresholding to identify a cystic region of interest from chest CT of LAM
      patients. Individual cysts were then extracted from the cystic region by the
      watershed algorithm, which separates individual cysts based on subtle edges
      within the cystic regions. A family of measurements were then computed, which
      quantify the amount, distribution, and boundary appearance of the cysts.
      Sequential floating feature selection was used to select a small subset of
      features for quantification of the severity of LAM. Adjusted R(2) from multiple
      linear regression and R(2) from linear regression against measurements from
      spirometry were used to compare the performance of our proposed measurements with
      currently used density based CT measurements in the literature, namely, the
      relative area measure and the D measure. RESULTS: Volumetric CT data, performed
      at total lung capacity and residual volume, from a total of 49 subjects enrolled
      in the MILES trial were used in our study. Our proposed measures had adjusted
      R(2) ranging from 0.42 to 0.59 when regressing against the spirometry measures,
      with p < 0.05. For previously used density based CT measurements in the
      literature, the best R(2) was 0.46 (for only one instance), with the majority
      being lower than 0.3 or p > 0.05. CONCLUSIONS: The proposed family of CT-based
      cyst measurements have better correlation with spirometric measures than
      previously used density based CT measurements. They show potential as a sensitive
      tool for quantitatively assessing the severity of LAM.

PMID- 25979024
TI  - Neural-network based autocontouring algorithm for intrafractional lung-tumor
      tracking using Linac-MR.
AB  - PURPOSE: To develop a neural-network based autocontouring algorithm for
      intrafractional lung-tumor tracking using Linac-MR and evaluate its performance
      with phantom and in-vivo MR images. METHODS: An autocontouring algorithm was
      developed to determine both the shape and position of a lung tumor from each
      intrafractional MR image. A pulse-coupled neural network was implemented in the
      algorithm for contrast improvement of the tumor region. Prior to treatment, to
      initiate the algorithm, an expert user needs to contour the tumor and its maximum
      anticipated range of motion in pretreatment MR images. During treatment, however,
      the algorithm processes each intrafractional MR image and automatically generates
      a tumor contour without further user input. The algorithm is designed to produce
      a tumor contour that is the most similar to the expert's manual one. To evaluate
      the autocontouring algorithm in the author's Linac-MR environment which utilizes
      a 0.5 T MRI, a motion phantom and four lung cancer patients were imaged with 3 T
      MRI during normal breathing, and the image noise was degraded to reflect the
      image noise at 0.5 T. Each of the pseudo-0.5 T images was autocontoured using the
      author's algorithm. In each test image, the Dice similarity index (DSI) and
      Hausdorff distance (HD) between the expert's manual contour and the algorithm
      generated contour were calculated, and their centroid positions were compared
      (Deltad centroid). RESULTS: The algorithm successfully contoured the shape of a
      moving tumor from dynamic MR images acquired every 275 ms. From the phantom
      study, mean DSI of 0.95-0.96, mean HD of 2.61-2.82 mm, and mean Deltad centroid
      of 0.68-0.93 mm were achieved. From the in-vivo study, the author's algorithm
      achieved mean DSI of 0.87-0.92, mean HD of 3.12-4.35 mm, as well as Deltad
      centroid of 1.03-1.35 mm. Autocontouring speed was less than 20 ms for each
      image. CONCLUSIONS: The authors have developed and evaluated a lung tumor
      autocontouring algorithm for intrafractional tumor tracking using Linac-MR. The
      autocontouring performance in the Linac-MR environment was evaluated using
      phantom and in-vivo MR images. From the in-vivo study, the author's algorithm
      achieved 87%-92% of contouring agreement and centroid tracking accuracy of 1.03
      1.35 mm. These results demonstrate the feasibility of lung tumor autocontouring
      in the author's laboratory's Linac-MR environment.

PMID- 25979025
TI  - Gamma Knife irradiation method based on dosimetric controls to target small areas
      in rat brains.
AB  - PURPOSE: Targeted and whole-brain irradiation in humans can result in significant
      side effects causing decreased patient quality of life. To adequately investigate
      structural and functional alterations after stereotactic radiosurgery,
      preclinical studies are needed. The purpose of this work is to establish a robust
      standardized method of targeted irradiation on small regions of the rat brain.
      METHODS: Euthanized male Fischer rats were imaged in a stereotactic bed, by
      computed tomography (CT), to estimate positioning variations relative to the
      bregma skull reference point. Using a rat brain atlas and the stereotactic bregma
      coordinates obtained from CT images, different regions of the brain were
      delimited and a treatment plan was generated. A single isocenter treatment plan
      delivering >= 100 Gy in 100% of the target volume was produced by Leksell
      GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the
      Gamma Knife unit. Impact of positioning deviations of the rat brain on dose
      deposition was simulated by GammaPlan and validated with dosimetric measurements.
      RESULTS: The authors' results showed that 90% of the target volume received 100
      +/- 8 Gy and the maximum of deposited dose was 125 +/- 0.7 Gy, which corresponds
      to an excellent relative standard deviation of 0.6%. This dose deposition
      calculated with GammaPlan was validated with dosimetric films resulting in a dose
      profile agreement within 5%, both in X- and Z-axes. CONCLUSIONS: The authors'
      results demonstrate the feasibility of standardizing the irradiation procedure of
      a small volume in the rat brain using a Gamma Knife.

PMID- 25979026
TI  - Dynamic trajectory-based couch motion for improvement of radiation therapy
      trajectories in cranial SRT.
AB  - PURPOSE: To investigate potential improvement in external beam stereotactic
      radiation therapy plan quality for cranial cases using an optimized dynamic
      gantry and patient support couch motion trajectory, which could minimize exposure
      to sensitive healthy tissue. METHODS: Anonymized patient anatomy and treatment
      plans of cranial cancer patients were used to quantify the geometric overlap
      between planning target volumes and organs-at-risk (OARs) based on their two
      dimensional projection from source to a plane at isocenter as a function of
      gantry and couch angle. Published dose constraints were then used as weighting
      factors for the OARs to generate a map of couch-gantry coordinate space,
      indicating degree of overlap at each point in space. A couch-gantry collision
      space was generated by direct measurement on a linear accelerator and couch using
      an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm
      was written to generate a navigable ideal trajectory for the patient specific
      couch-gantry space. The advanced algorithm can be used to balance the
      implementation of absolute minimum values of overlap with the clinical
      practicality of large-scale couch motion and delivery time. Optimized cranial
      cancer treatment trajectories were compared to conventional treatment
      trajectories. RESULTS: Comparison of optimized treatment trajectories with
      conventional treatment trajectories indicated an average decrease in mean dose to
      the OARs of 19% and an average decrease in maximum dose to the OARs of 12%.
      Degradation was seen for homogeneity index (6.14% +/- 0.67%-5.48% +/- 0.76%) and
      conformation number (0.82 +/- 0.02-0.79 +/- 0.02), but neither was statistically
      significant. Removal of OAR constraints from volumetric modulated arc therapy
      optimization reveals that reduction in dose to OARs is almost exclusively due to
      the optimized trajectory and not the OAR constraints. CONCLUSIONS: The authors'
      study indicated that simultaneous couch and gantry motion during radiation
      therapy to minimize the geometrical overlap in the beams-eye-view of target
      volumes and the organs-at-risk can have an appreciable dose reduction to organs
      at-risk.

PMID- 25979027
TI  - The performance of normal-tissue complication probability models in the presence
      of confounding factors.
AB  - PURPOSE: This work explores different methods for accounting for patient-specific
      factors in normal-tissue complication probability (NTCP) modeling, and compares
      the performance of models using pseudoclinical datasets for "lung" and "rectum"
      complications. METHODS: Datasets consisting of dose distributions and resulting
      normal-tissue complications were simulated, letting varying levels of confounding
      factors (i.e., nondosimetric factors) influence the outcome. The simulated
      confounding factors were patient radiosensitivity and health status. Seven
      empirical NTCP models were fitted to each dataset; this is analogous to fitting
      alternative models to datasets from different populations, treated with the same
      technique. The performance of these models was compared using the area under the
      ROC curve (AUC) and the impact of confounding factors on the model performance
      was studied. The patient-specific factors were then accounted for by (1)
      stratification and (2) two ways of modifying the traditional NTCP models to
      include these factors. RESULTS: Confounding factors had a greater impact on model
      performance than the choice of model. All models performed similarly well on the
      rectum datasets (except the maximum dose model), while critical-volume type
      models were slightly better than the mean dose-, the Lyman-Kutcher-Burman-, and
      the relative seriality models for lung. This difference was more apparent without
      confounding factors in the dataset. The two alternative functions including
      patient-specific factors used in this work (one logistic and one cumulative
      normal function) were found to be equivalent, and more efficient than stratifying
      datasets according to patient-specific factors and fitting models to subgroups
      individually. For datasets including confounding factors, the performance
      improved greatly when using models accounting for these; AUC increased from
      around 0.7 to close to unity. CONCLUSIONS: This work shows that identifying
      confounding factors, and developing methods to quantify them, is more important
      than the choice of NTCP model. Most dose-volume histogram (DVH)-based NTCP models
      can be generalized to include confounding factors.

PMID- 25979028
TI  - Technical Note: Experimental carbon ion range verification in inhomogeneous
      phantoms using prompt gammas.
AB  - PURPOSE: The purpose of this study was to experimentally assess the possibility
      to monitor carbon ion range variations--due to tumor shift and/or elongation or
      shrinking--using prompt-gamma (PG) emission with inhomogeneous phantoms. Such a
      study is related to the development of PG monitoring techniques to be used in a
      carbon ion therapy context. METHODS: A 95 MeV/u carbon ion beam was used to
      irradiate phantoms with a variable density along the ion path to mimic the
      presence of bone and lung in homogeneous humanlike tissue. PG profiles were
      obtained after a longitudinal scan of the phantoms. A setup comprising a narrow
      single-slit collimator and two detectors placed at 90 degrees  with respect to
      the beam axis was used. The time of flight technique was applied to allow the
      selection between PG and background events. RESULTS: Using the positions at 50%
      entrance and 50% falloff of the PG profiles, a quantity called prompt-gamma
      profile length (PGPL) is defined. It is possible to observe shifts in the PGPL
      when there are absolute ion range shifts as small as 1-2 mm. Quantitatively, for
      an ion range shift of -1.33 +/- 0.46 mm (insertion of a Teflon slab), a PGPL
      difference of -1.93 +/- 0.58 mm and -1.84 +/- 1.27 mm is obtained using a BaF2
      and a NaI(Tl) detector, respectively. In turn, when an ion range shift of 4.59 +/
      0.42 mm (insertion of a lung-equivalent material slab) is considered, the
      difference is of 4.10 +/- 0.54 and 4.39 +/- 0.80 mm for the same detectors.
      CONCLUSIONS: Herein, experimental evidence of the usefulness of employing PG to
      monitor carbon ion range using inhomogeneous phantoms is presented. Considering
      the homogeneous phantom as reference, the results show that the information
      provided by the PG emission allows for detecting ion range shifts as small as 1-2
      mm. When considering the expected PG emission from an energy slice in a carbon
      ion therapy scenario, the experimental setup would allow to retrieve the same
      PGPL as the high statistics of the full experimental dataset in 58% of the times.
      However, this success rate increases to 93% when using a better optimized setup
      by means of Monte Carlo simulations.

PMID- 25979029
TI  - Imaging a moving lung tumor with megavoltage cone beam computed tomography.
AB  - PURPOSE: Respiratory motion may affect the accuracy of image guidance of
      radiation treatment of lung cancer. A cone beam computed tomography (CBCT) image
      spans several breathing cycles, resulting in a blurred object with a theoretical
      size equal to the sum of tumor size and breathing motion. However, several
      factors may affect this theoretical relationship. The objective of this study was
      to analyze the effect of tumor motion on megavoltage (MV)-CBCT images, by
      comparing target sizes on simulation and pretreatment images of a large cohort of
      lung cancer patients. METHODS: Ninety-three MV-CBCT images from 17 patients were
      analyzed. Internal target volumes were contoured on each MV-CBCT dataset
      [internal target volume (ITVCB)]. Their extent in each dimension was compared to
      that of two volumes contoured on simulation 4-dimensional computed tomography (4D
      CT) images: the combination of the tumor contours of each phase of the 4D-CT
      (ITV4D) and the volume contoured on the average CT calculated from the 4D-CT
      phases (ITVave). Tumor size and breathing amplitude were assessed by contouring
      the tumor on each CBCT raw projection where it could be unambiguously identified.
      The effect of breathing amplitude on the quality of the MV-CBCT image
      reconstruction was analyzed. RESULTS: The mean differences between the sizes of
      ITVCB and ITV4D were -1.6 +/- 3.3 mm (p < 0.001), -2.4 +/- 3.1 mm (p < 0.001),
      and -7.2 +/- 5.3 mm (p < 0.001) in the anterior/posterior (AP), left/right (LR),
      and superior/inferior (SI) directions, respectively, showing that MV-CBCT
      underestimates the full target size. The corresponding mean differences between
      ITVCB and ITVave were 0.3 +/- 2.6 mm (p = 0.307), 0.0 +/- 2.4 mm (p = 0.86), and 
      4.0 +/- 4.3 mm (p < 0.001), indicating that the average CT image is more
      representative of what is visible on MV-CBCT in the AP and LR directions. In the
      SI directions, differences between ITVCB and ITVave could be separated into two
      groups based on tumor motion: -3.2 +/- 3.2 mm for tumor motion less than 15 mm
      and -10.9 +/- 6.3 mm for tumor motion greater than 15 mm. Deviations of measured
      target extents from their theoretical values derived from tumor size and motion
      were correlated with motion amplitude similarly for both MV-CBCT and average CT
      images, suggesting that the two images were subject to similar motion artifacts
      for motion less than 15 mm. CONCLUSIONS: MV-CBCT images are affected by tumor
      motion and tend to under-represent the full target volume. For tumor motion up to
      15 mm, the volume contoured on average CT is comparable to that contoured on the
      MV-CBCT. Therefore, the average CT should be used in image registration for
      localization purposes, and the standard 5 mm PTV margin seems adequate. For tumor
      motion greater than 15 mm, an additional setup margin may need to be used to
      account for the increased uncertainty in tumor localization.

PMID- 25979030
TI  - Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of
      human brain.
AB  - PURPOSE: The purpose of this study was to develop a dual-modality positron
      emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET
      for simultaneous PET and MR imaging of the human brain. METHODS: The PET detector
      block was composed of a 4 * 4 matrix of detector modules, each consisting of a 4
      * 4 array LYSO coupled to a 4 * 4 Geiger-mode avalanche photodiode (GAPD) array.
      The PET insert consisted of 18 detector blocks, circularly mounted on a custom
      made plastic base to form a ring with an inner diameter of 390 mm and axial
      length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric
      tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred
      via 4 m long flat cables were fed into the position decoder circuit. The flat
      cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm.
      The position decoder circuit and field programmable gate array-embedded DAQ
      modules were enclosed in an aluminum box with a thickness of 10 mm and located at
      the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor
      frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI
      hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of
      25 cm was fabricated. The PET was positioned between gradient and the RF coils.
      PET performance was measured outside and inside the MRI scanner using echo planar
      imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance
      was also evaluated with and without the PET insert. The stability of the newly
      developed PET insert was evaluated and simultaneous PET and MR images of a brain
      phantom were acquired. RESULTS: No significant degradation of the PET performance
      caused by MR was observed when the PET was operated using various MR imaging
      sequences. The signal-to-noise ratio of MR images was slightly degraded due to
      the PET insert installed inside the MR bore while the homogeneity was maintained.
      The change of gain of the 256 GAPD/scintillator elements of a detector block was
      <3% for 60 min, and simultaneous PET and MR images of a brain phantom were
      successfully acquired. CONCLUSIONS: Experimental results indicate that a compact
      and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays
      and charge signal transmission method proposed in this study without significant
      interference.

PMID- 25979031
TI  - Technical Note: On the proton range and nuclear interactions in compounds and
      mixtures.
AB  - PURPOSE: Range and probability of nonelastic nuclear interactions (NNIs) for
      protons can be found only for a limited number of compounds and mixtures in
      nuclear data tables, and the proton-related analytical studies are therefore
      restricted to those materials for which the data are provided in these documents.
      In this paper, the authors present general solutions for calculating the proton
      range and probability of NNIs for desired compounds and mixtures. METHODS:
      Benefiting from the Bragg-Kleeman approximation of mass stopping power, the
      authors derive a concise formula for calculating the proton range in materials
      with arbitrary number of constituent elements. Additionally, the authors propose
      another relation for obtaining the probability of undergoing NNIs which is
      suggested to be additive. RESULTS: The examination of the formula presented shows
      that the authors' method can be considered as general solutions for analytical
      evaluation of the range in compounds and mixtures. The formula proposed for
      probability of NNIs is valid for almost every compound except for those materials
      containing H. It is shown that this formula can be modified so that it covers
      these materials. CONCLUSIONS: The authors present a general analytical method for
      calculating the range and probability of NNIs for protons which are
      mathematically easy to handle and valid for desired compounds or mixtures
      composed of an arbitrary number of constituent elements, including materials of
      interest for proton radiotherapy purposes.

PMID- 25979033
TI  - Impact of the differential fluence distribution of brachytherapy sources on the
      spectroscopic dose-rate constant.
AB  - PURPOSE: To investigate why dose-rate constants for (125)I and (103)Pd seeds
      computed using the spectroscopic technique, Lambda spec, differ from those
      computed with standard Monte Carlo (MC) techniques. A potential cause of these
      discrepancies is the spectroscopic technique's use of approximations of the true
      fluence distribution leaving the source, phi full. In particular, the fluence
      distribution used in the spectroscopic technique, phi spec, approximates the
      spatial, angular, and energy distributions of phi full. This work quantified the
      extent to which each of these approximations affects the accuracy of Lambda spec.
      Additionally, this study investigated how the simplified water-only model used in
      the spectroscopic technique impacts the accuracy of Lambda spec. METHODS: Dose
      rate constants as described in the AAPM TG-43U1 report, Lambda full, were
      computed with MC simulations using the full source geometry for each of 14
      different (125)I and 6 different (103)Pd source models. In addition, the spectrum
      emitted along the perpendicular bisector of each source was simulated in vacuum
      using the full source model and used to compute Lambda spec. Lambda spec was
      compared to Lambda full to verify the discrepancy reported by Rodriguez and
      Rogers. Using MC simulations, a phase space of the fluence leaving the
      encapsulation of each full source model was created. The spatial and angular
      distributions of phi full were extracted from the phase spaces and were
      qualitatively compared to those used by phi spec. Additionally, each phase space
      was modified to reflect one of the approximated distributions (spatial, angular,
      or energy) used by phi spec. The dose-rate constant resulting from using
      approximated distribution i, Lambda approx,i, was computed using the modified
      phase space and compared to Lambda full. For each source, this process was
      repeated for each approximation in order to determine which approximations used
      in the spectroscopic technique affect the accuracy of Lambda spec. RESULTS: For
      all sources studied, the angular and spatial distributions of phi full were more
      complex than the distributions used in phi spec. Differences between Lambda spec
      and Lambda full ranged from -0.6% to +6.4%, confirming the discrepancies found by
      Rodriguez and Rogers. The largest contribution to the discrepancy was the
      assumption of isotropic emission in phi spec, which caused differences in Lambda
      of up to +5.3% relative to Lambda full. Use of the approximated spatial and
      energy distributions caused smaller average discrepancies in Lambda of -0.4% and
      +0.1%, respectively. The water-only model introduced an average discrepancy in
      Lambda of -0.4%. CONCLUSIONS: The approximations used in phi spec caused
      discrepancies between Lambda approx,i and Lambda full of up to 7.8%. With the
      exception of the energy distribution, the approximations used in phi spec
      contributed to this discrepancy for all source models studied. To improve the
      accuracy of Lambda spec, the spatial and angular distributions of phi full could
      be measured, with the measurements replacing the approximated distributions. The
      methodology used in this work could be used to determine the resolution that such
      measurements would require by computing the dose-rate constants from phase spaces
      modified to reflect phi full binned at different spatial and angular resolutions.

PMID- 25979032
TI  - Automated prostate cancer detection using T2-weighted and high-b-value diffusion
      weighted magnetic resonance imaging.
AB  - PURPOSE: The authors propose a computer-aided diagnosis (CAD) system for prostate
      cancer to aid in improving the accuracy, reproducibility, and standardization of
      multiparametric magnetic resonance imaging (MRI). METHODS: The proposed system
      utilizes two MRI sequences [T2-weighted MRI and high-b-value (b = 2000 s/mm(2))
      diffusion-weighted imaging (DWI)] and texture features based on local binary
      patterns. A three-stage feature selection method is employed to provide the most
      discriminative features. The authors included a total of 244 patients. Training
      the CAD system on 108 patients (78 MR-positive prostate cancers and 105 benign MR
      positive lesions), two validation studies were retrospectively performed on 136
      patients (68 MR-positive prostate cancers, 111 benign MR-positive lesions, and
      117 MR-negative benign lesions). RESULTS: In distinguishing cancer from MR
      positive benign lesions, an area under receiver operating characteristic curve
      (AUC) of 0.83 [95% confidence interval (CI): 0.76-0.89] was achieved. For cancer
      vs MR-positive or MR-negative benign lesions, the authors obtained an AUC of 0.89
      AUC (95% CI: 0.84-0.93). The performance of the CAD system was not dependent on
      the specific regions of the prostate, e.g., a peripheral zone or transition zone.
      Moreover, the CAD system outperformed other combinations of MRI sequences: T2W
      MRI, high-b-value DWI, and the standard apparent diffusion coefficient (ADC) map
      of DWI. CONCLUSIONS: The novel CAD system is able to detect the discriminative
      texture features for cancer detection and localization and is a promising tool
      for improving the quality and efficiency of prostate cancer diagnosis.

PMID- 25979034
TI  - A Monte Carlo simulation framework for electron beam dose calculations using
      Varian phase space files for TrueBeam Linacs.
AB  - PURPOSE: To develop a framework for accurate electron Monte Carlo dose
      calculation. In this study, comprehensive validations of vendor provided electron
      beam phase space files for Varian TrueBeam Linacs against measurement data are
      presented. METHODS: In this framework, the Monte Carlo generated phase space
      files were provided by the vendor and used as input to the downstream plan
      specific simulations including jaws, electron applicators, and water phantom
      computed in the EGSnrc environment. The phase space files were generated based on
      open field commissioning data. A subset of electron energies of 6, 9, 12, 16, and
      20 MeV and open and collimated field sizes 3 * 3, 4 * 4, 5 * 5, 6 * 6, 10 * 10,
      15 * 15, 20 * 20, and 25 * 25 cm(2) were evaluated. Measurements acquired with a
      CC13 cylindrical ionization chamber and electron diode detector and simulations
      from this framework were compared for a water phantom geometry. The evaluation
      metrics include percent depth dose, orthogonal and diagonal profiles at depths
      R100, R50, Rp, and Rp+ for standard and extended source-to-surface distances
      (SSD), as well as cone and cut-out output factors. RESULTS: Agreement for the
      percent depth dose and orthogonal profiles between measurement and Monte Carlo
      was generally within 2% or 1 mm. The largest discrepancies were observed within
      depths of 5 mm from phantom surface. Differences in field size, penumbra, and
      flatness for the orthogonal profiles at depths R100, R50, and Rp were within 1
      mm, 1 mm, and 2%, respectively. Orthogonal profiles at SSDs of 100 and 120 cm
      showed the same level of agreement. Cone and cut-out output factors agreed well
      with maximum differences within 2.5% for 6 MeV and 1% for all other energies.
      Cone output factors at extended SSDs of 105, 110, 115, and 120 cm exhibited
      similar levels of agreement. CONCLUSIONS: We have presented a Monte Carlo
      simulation framework for electron beam dose calculations for Varian TrueBeam
      Linacs. Electron beam energies of 6 to 20 MeV for open and collimated field sizes
      from 3 * 3 to 25 * 25 cm(2) were studied and results were compared to the
      measurement data with excellent agreement. Application of this framework can thus
      be used as the platform for treatment planning of dynamic electron arc
      radiotherapy and other advanced dynamic techniques with electron beams.

PMID- 25979035
TI  - Characterization of a high-energy in-line phase contrast tomosynthesis prototype.
AB  - PURPOSE: In this research, a high-energy in-line phase contrast tomosynthesis
      prototype was developed and characterized through quantitative investigations and
      phantom studies. METHODS: The prototype system consists of an x-ray source, a
      motorized rotation stage, and a CMOS detector with a pixel pitch of 0.05 mm. The
      x-ray source was operated at 120 kVp for this study, and the objects were mounted
      on the rotation stage 76.2 cm (R1) from the source and 114.3 cm (R2) from the
      detector. The large air gap between the object and detector guarantees sufficient
      phase-shift effects. The quantitative evaluation of this prototype included
      modulation transfer function and noise power spectrum measurements conducted
      under both projection mode and tomosynthesis mode. Phantom studies were performed
      including three custom designed phantoms with complex structures: a five-layer
      bubble wrap phantom, a fishbone phantom, and a chicken breast phantom with
      embedded fibrils and mass structures extracted from an ACR phantom. In-plane
      images of the phantoms were acquired to investigate their image qualities through
      observation, intensity profile plots, edge enhancement evaluations, and/or
      contrast-to-noise ratio calculations. In addition, the robust phase-attenuation
      duality (PAD)-based phase retrieval method was applied to tomosynthesis for the
      first time in this research. It was utilized as a preprocessing method to fully
      exhibit phase contrast on the angular projection before reconstruction. RESULTS:
      The resolution and noise characteristics of this high-energy in-line phase
      contrast tomosynthesis prototype were successfully investigated and demonstrated.
      The phantom studies demonstrated that this imaging prototype can successfully
      remove the structure overlapping in phantom projections, obtain delineate
      interfaces, and achieve better contrast-to-noise ratio after applying phase
      retrieval to the angular projections. CONCLUSIONS: This research successfully
      demonstrated a high-energy in-line phase contrast tomosynthesis prototype. In
      addition, the PAD-based method of phase retrieval was combined with tomosynthesis
      imaging for the first time, which demonstrated its capability in significantly
      improving the contrast-to-noise ratios in the images.

PMID- 25979036
TI  - Bayesian network ensemble as a multivariate strategy to predict radiation
      pneumonitis risk.
AB  - PURPOSE: Prediction of radiation pneumonitis (RP) has been shown to be
      challenging due to the involvement of a variety of factors including dose-volume
      metrics and radiosensitivity biomarkers. Some of these factors are highly
      correlated and might affect prediction results when combined. Bayesian network
      (BN) provides a probabilistic framework to represent variable dependencies in a
      directed acyclic graph. The aim of this study is to integrate the BN framework
      and a systems' biology approach to detect possible interactions among RP risk
      factors and exploit these relationships to enhance both the understanding and
      prediction of RP. METHODS: The authors studied 54 nonsmall-cell lung cancer
      patients who received curative 3D-conformal radiotherapy. Nineteen RP events were
      observed (common toxicity criteria for adverse events grade 2 or higher). Serum
      concentration of the following four candidate biomarkers were measured at
      baseline and midtreatment: alpha-2-macroglobulin, angiotensin converting enzyme
      (ACE), transforming growth factor, interleukin-6. Dose-volumetric and clinical
      parameters were also included as covariates. Feature selection was performed
      using a Markov blanket approach based on the Koller-Sahami filter. The Markov
      chain Monte Carlo technique estimated the posterior distribution of BN graphs
      built from the observed data of the selected variables and causality constraints.
      RP probability was estimated using a limited number of high posterior graphs
      (ensemble) and was averaged for the final RP estimate using Bayes' rule. A
      resampling method based on bootstrapping was applied to model training and
      validation in order to control under- and overfit pitfalls. RESULTS: RP
      prediction power of the BN ensemble approach reached its optimum at a size of
      200. The optimized performance of the BN model recorded an area under the
      receiver operating characteristic curve (AUC) of 0.83, which was significantly
      higher than multivariate logistic regression (0.77), mean heart dose (0.69), and
      a pre-to-midtreatment change in ACE (0.66). When RP prediction was made only with
      pretreatment information, the AUC ranged from 0.76 to 0.81 depending on the
      ensemble size. Bootstrap validation of graph features in the ensemble quantified
      confidence of association between variables in the graphs where ten interactions
      were statistically significant. CONCLUSIONS: The presented BN methodology
      provides the flexibility to model hierarchical interactions between RP
      covariates, which is applied to probabilistic inference on RP. The authors'
      preliminary results demonstrate that such framework combined with an ensemble
      method can possibly improve prediction of RP under real-life clinical
      circumstances such as missing data or treatment plan adaptation.

PMID- 25979037
TI  - Fast segmentation of the femoral arteries from 3D MR images: A tool for rapid
      assessment of peripheral arterial disease.
AB  - PURPOSE: The peripheral arterial disease is a powerful indicator of coexistent
      generalized atherosclerosis. As plaques in femoral arteries are diffused and can
      span a length of 30 cm, a large coverage of the arteries is required to assess
      the full extent of atherosclerosis. Recent development of 3D black-blood magnetic
      resonance imaging sequences has allowed fast acquisition of images with an
      extended longitudinal coverage. Vessel wall volume quantification requires the
      segmentation of the lumen and outer wall boundaries, and conventional manual
      planimetry would be too time-consuming to be feasible for analyzing images with
      such a large coverage. To address this challenge in image analysis, this work
      introduces an efficient 3D algorithm to segment the lumen and outer wall
      boundaries for plaque and vessel wall quantification in the femoral artery.
      METHODS: To generate the initial lumen surface, a user identified the location of
      the lumen centers manually on a set of transverse images with a user-specified
      interslice distance (ISD). A number of geometric operators were introduced to
      automatically adjust the initial lumen surface based on pixel intensity and
      gradient along the boundary and at the center of each transverse slice. The
      adjusted surface was optimized by a 3D deformable model driven by the local
      stiffness force and external force based on image gradient. The optimized lumen
      surface was expanded to obtain the initial outer wall surface, which was
      subsequently optimized by the 3D deformable model. RESULTS: The algorithm was
      executed with and without adjustment of the initial lumen surface and for three
      different selections of ISD: 10, 20, and 30 mm. The segmentation accuracy was
      improved in a statistically significant way with the introduction of initial
      lumen surface adjustment, but was insensitive to the ISD setting. When compared
      with the manual segmentation, the settings with adjustment have, on average, mean
      absolute differences (MADs) of 0.28 and 0.36 mm, respectively, for lumen and
      outer wall segmentations, which are significantly lower than those obtained when
      the adjustment operators were not applied (MAD = 0.43 and 0.59 mm for lumen and
      outer wall segmentations). The algorithm took about 1% of the time required for
      manual segmentation to complete segmenting the whole 3D femoral artery.
      CONCLUSIONS: The proposed semiautomatic algorithm generated accurate lumen and
      outer wall boundaries from 3D black-blood MR images with few user interactions,
      thereby allowing rapid and streamlined assessment of plaque burden in the femoral
      arteries.

PMID- 25979038
TI  - Failure mode and effects analysis and fault tree analysis of surface image guided
      cranial radiosurgery.
AB  - PURPOSE: Surface image guided, Linac-based radiosurgery (SIG-RS) is a modern
      approach for delivering radiosurgery that utilizes optical stereoscopic imaging
      to monitor the surface of the patient during treatment in lieu of using a head
      frame for patient immobilization. Considering the novelty of the SIG-RS approach
      and the severity of errors associated with delivery of large doses per fraction,
      a risk assessment should be conducted to identify potential hazards, determine
      their causes, and formulate mitigation strategies. The purpose of this work is to
      investigate SIG-RS using the combined application of failure modes and effects
      analysis (FMEA) and fault tree analysis (FTA), report on the effort required to
      complete the analysis, and evaluate the use of FTA in conjunction with FMEA.
      METHODS: A multidisciplinary team was assembled to conduct the FMEA on the SIG-RS
      process. A process map detailing the steps of the SIG-RS was created to guide the
      FMEA. Failure modes were determined for each step in the SIG-RS process, and risk
      priority numbers (RPNs) were estimated for each failure mode to facilitate risk
      stratification. The failure modes were ranked by RPN, and FTA was used to
      determine the root factors contributing to the riskiest failure modes. Using the
      FTA, mitigation strategies were formulated to address the root factors and reduce
      the risk of the process. The RPNs were re-estimated based on the mitigation
      strategies to determine the margin of risk reduction. RESULTS: The FMEA and FTAs
      for the top two failure modes required an effort of 36 person-hours (30 person
      hours for the FMEA and 6 person-hours for two FTAs). The SIG-RS process consisted
      of 13 major subprocesses and 91 steps, which amounted to 167 failure modes. Of
      the 91 steps, 16 were directly related to surface imaging. Twenty-five failure
      modes resulted in a RPN of 100 or greater. Only one of these top 25 failure modes
      was specific to surface imaging. The riskiest surface imaging failure mode had an
      overall RPN-rank of eighth. Mitigation strategies for the top failure mode
      decreased the RPN from 288 to 72. CONCLUSIONS: Based on the FMEA performed in
      this work, the use of surface imaging for monitoring intrafraction position in
      Linac-based stereotactic radiosurgery (SRS) did not greatly increase the risk of
      the Linac-based SRS process. In some cases, SIG helped to reduce the risk of
      Linac-based RS. The FMEA was augmented by the use of FTA since it divided the
      failure modes into their fundamental components, which simplified the task of
      developing mitigation strategies.

PMID- 25979039
TI  - Motion mitigation for lung cancer patients treated with active scanning proton
      therapy.
AB  - PURPOSE: Motion interplay can affect the tumor dose in scanned proton beam
      therapy. This study assesses the ability of rescanning and gating to mitigate
      interplay effects during lung treatments. METHODS: The treatments of five lung
      cancer patients [48 Gy(RBE)/4fx] with varying tumor size (21.1-82.3 cm(3)) and
      motion amplitude (2.9-30.6 mm) were simulated employing 4D Monte Carlo. The
      authors investigated two spot sizes (sigma ~ 12 and ~ 3 mm), three rescanning
      techniques (layered, volumetric, breath-sampled volumetric) and respiratory
      gating with a 30% duty cycle. RESULTS: For 4/5 patients, layered rescanning 6/2
      times (for the small/large spot size) maintains equivalent uniform dose within
      the target >98% for a single fraction. Breath sampling the timing of rescanning
      is ~ 2 times more effective than the same number of continuous rescans.
      Volumetric rescanning is sensitive to synchronization effects, which was observed
      in 3/5 patients, though not for layered rescanning. For the large spot size,
      rescanning compared favorably with gating in terms of time requirements, i.e., 2x
      rescanning is on average a factor ~ 2.6 faster than gating for this scenario. For
      the small spot size however, 6x-rescanning takes on average 65% longer compared
      to gating. Rescanning has no effect on normal lung V20 and mean lung dose (MLD),
      though it reduces the maximum lung dose by on average 6.9 +/- 2.4/16.7 +/- 12.2
      Gy(RBE) for the large and small spot sizes, respectively. Gating leads to a
      similar reduction in maximum dose and additionally reduces V20 and MLD. Breath
      sampled rescanning is most successful in reducing the maximum dose to the normal
      lung. CONCLUSIONS: Both rescanning (2-6 times, depending on the beam size) as
      well as gating was able to mitigate interplay effects in the target for 4/5
      patients studied. Layered rescanning is superior to volumetric rescanning, as the
      latter suffers from synchronization effects in 3/5 patients studied. Gating
      minimizes the irradiated volume of normal lung more efficiently, while breath
      sampled rescanning is superior in reducing maximum doses to organs at risk.

PMID- 25979040
TI  - Biomechanical modeling constrained surface-based image registration for prostate
      MR guided TRUS biopsy.
AB  - PURPOSE: Adding magnetic resonance (MR)-derived information to standard
      transrectal ultrasound (TRUS) images for guiding prostate biopsy is of
      substantial clinical interest. A tumor visible on MR images can be projected on
      ultrasound (US) by using MR-US registration. A common approach is to use surface
      based registration. The authors hypothesize that biomechanical modeling will
      better control deformation inside the prostate than a regular nonrigid surface
      based registration method. The authors developed a novel method by extending a
      nonrigid surface-based registration algorithm with biomechanical finite element
      (FE) modeling to better predict internal deformations of the prostate. METHODS:
      Data were collected from ten patients and the MR and TRUS images were rigidly
      registered to anatomically align prostate orientations. The prostate was manually
      segmented in both images and corresponding surface meshes were generated. Next, a
      tetrahedral volume mesh was generated from the MR image. Prostate deformations
      due to the TRUS probe were simulated using the surface displacements as the
      boundary condition. A three-dimensional thin-plate spline deformation field was
      calculated by registering the mesh vertices. The target registration errors
      (TREs) of 35 reference landmarks determined by surface and volume mesh
      registrations were compared. RESULTS: The median TRE of a surface-based
      registration with biomechanical regularization was 2.76 (0.81-7.96) mm. This was
      significantly different than the median TRE of 3.47 (1.05-7.80) mm for regular
      surface-based registration without biomechanical regularization. CONCLUSIONS:
      Biomechanical FE modeling has the potential to improve the accuracy of multimodal
      prostate registration when comparing it to a regular nonrigid surface-based
      registration algorithm and can help to improve the effectiveness of MR guided
      TRUS biopsy procedures.

PMID- 25979042
TI  - Estimating pediatric entrance skin dose from digital radiography examination
      using DICOM metadata: A quality assurance tool.
AB  - PURPOSE: To develop an automated methodology to estimate patient examination dose
      in digital radiography (DR) imaging using DICOM metadata as a quality assurance
      (QA) tool. METHODS: Patient examination and demographical information were
      gathered from metadata analysis of DICOM header data. The x-ray system radiation
      output (i.e., air KERMA) was characterized for all filter combinations used for
      patient examinations. Average patient thicknesses were measured for head, chest,
      abdomen, knees, and hands using volumetric images from CT. Backscatter factors
      (BSFs) were calculated from examination kVp. Patient entrance skin air KERMA
      (ESAK) was calculated by (1) looking up examination technique factors taken from
      DICOM header metadata (i.e., kVp and mA s) to derive an air KERMA (k air) value
      based on an x-ray characteristic radiation output curve; (2) scaling k air with a
      BSF value; and (3) correcting k air for patient thickness. Finally, patient
      entrance skin dose (ESD) was calculated by multiplying a mass-energy attenuation
      coefficient ratio by ESAK. Patient ESD calculations were computed for common DR
      examinations at our institution: dual view chest, anteroposterior (AP) abdomen,
      lateral (LAT) skull, dual view knee, and bone age (left hand only) examinations.
      RESULTS: ESD was calculated for a total of 3794 patients; mean age was 11 +/- 8
      yr (range: 2 months to 55 yr). The mean ESD range was 0.19-0.42 mGy for dual view
      chest, 0.28-1.2 mGy for AP abdomen, 0.18-0.65 mGy for LAT view skull, 0.15-0.63
      mGy for dual view knee, and 0.10-0.12 mGy for bone age (left hand) examinations.
      CONCLUSIONS: A methodology combining DICOM header metadata and basic x-ray tube
      characterization curves was demonstrated. In a regulatory era where patient dose
      reporting has become increasingly in demand, this methodology will allow a
      knowledgeable user the means to establish an automatable dose reporting program
      for DR and perform patient dose related QA testing for digital x-ray imaging.

PMID- 25979041
TI  - Dynamic contrast-enhanced MR microscopy identifies regions of therapeutic
      response in a preclinical model of colorectal adenocarcinoma.
AB  - PURPOSE: A typical dynamic contrast-enhanced (DCE)-MRI study often compares the
      derived pharmacokinetic parameters on manually selected tumor regions or over the
      entire tumor volume. These measurements include domains where the interpretation
      of the biomarkers may be unclear (such as in necrotic areas). Here, the authors
      describe a technique for increasing the sensitivity and specificity of DCE-MRI by
      identifying tumor regions with a variable response to therapy. METHODS: Two
      cohorts (n = 8/group) of nu/nu mice with LS-174T implanted in the mammary fat pad
      were imaged at five time points over four weeks. The treatment/control group
      received bevacizumab/saline at a dose of 5 mg/kg or 5 ml/kg twice weekly; imaging
      experiments were performed weekly. MR images were acquired at an isotropic
      resolution of 156 MUm(3)(2.4 nl) and with a sampling rate of 9.9 s. The histogram
      of the time-to-peak (TTP) was used to identify two (fast- and slow-enhancing)
      regions based on a threshold of TTP = 1000 s. The regions were correlated with
      histology, and the effect of therapy was locally examined. RESULTS: Tumors in the
      treatment group had a significantly longer doubling time. The regions defined by
      thresholding the TTP histogram identified two distinct domains correlating
      significantly with tumor permeability and microvessel density. In the fast
      enhancing region, the mean permeability constant (K(trans)) was significantly
      lower in the treatment group at day 9; in the slow-enhancing region, K(trans) was
      not different between the control and treatment groups. At day 9, the relative
      volume of the fast-enhancing region was significantly lower in the treatment
      group, while that of the slow-enhancing region was significantly higher.
      CONCLUSIONS: Two regions with distinct kinetic parameters were identified based
      on the histogram of TTP. The effect of bevacizumab, as measured by a decrease in
      K(trans), was confined to one of these regions. High spatiotemporal resolution MR
      studies may contribute unique insights into the response of the tumor
      microenvironment to therapy.

PMID- 25979044
TI  - Tracking tumor boundary in MV-EPID images without implanted markers: A
      feasibility study.
AB  - PURPOSE: To develop a markerless tracking algorithm to track the tumor boundary
      in megavoltage (MV)-electronic portal imaging device (EPID) images for image
      guided radiation therapy. METHODS: A level set method (LSM)-based algorithm is
      developed to track tumor boundary in EPID image sequences. Given an EPID image
      sequence, an initial curve is manually specified in the first frame. Driven by a
      region-scalable energy fitting function, the initial curve automatically evolves
      toward the tumor boundary and stops on the desired boundary while the energy
      function reaches its minimum. For the subsequent frames, the tracking algorithm
      updates the initial curve by using the tracking result in the previous frame and
      reuses the LSM to detect the tumor boundary in the subsequent frame so that the
      tracking processing can be continued without user intervention. The tracking
      algorithm is tested on three image datasets, including a 4-D phantom EPID image
      sequence, four digitally deformable phantom image sequences with different noise
      levels, and four clinical EPID image sequences acquired in lung cancer treatment.
      The tracking accuracy is evaluated based on two metrics: centroid localization
      error (CLE) and volume overlap index (VOI) between the tracking result and the
      ground truth. RESULTS: For the 4-D phantom image sequence, the CLE is 0.23 +/-
      0.20 mm, and VOI is 95.6% +/- 0.2%. For the digital phantom image sequences, the
      total CLE and VOI are 0.11 +/- 0.08 mm and 96.7% +/- 0.7%, respectively. In
      addition, for the clinical EPID image sequences, the proposed algorithm achieves
      0.32 +/- 0.77 mm in the CLE and 72.1% +/- 5.5% in the VOI. These results
      demonstrate the effectiveness of the authors' proposed method both in tumor
      localization and boundary tracking in EPID images. In addition, compared with two
      existing tracking algorithms, the proposed method achieves a higher accuracy in
      tumor localization. CONCLUSIONS: In this paper, the authors presented a
      feasibility study of tracking tumor boundary in EPID images by using a LSM-based
      algorithm. Experimental results conducted on phantom and clinical EPID images
      demonstrated the effectiveness of the tracking algorithm for visible tumor
      target. Compared with previous tracking methods, the authors' algorithm has the
      potential to improve the tracking accuracy in radiation therapy. In addition,
      real-time tumor boundary information within the irradiation field will be
      potentially useful for further applications, such as adaptive beam delivery, dose
      evaluation.

PMID- 25979043
TI  - A method for volumetric imaging in radiotherapy using single x-ray projection.
AB  - PURPOSE: It is an intriguing problem to generate an instantaneous volumetric
      image based on the corresponding x-ray projection. The purpose of this study is
      to develop a new method to achieve this goal via a sparse learning approach.
      METHODS: To extract motion information hidden in projection images, the authors
      partitioned a projection image into small rectangular patches. The authors
      utilized a sparse learning method to automatically select patches that have a
      high correlation with principal component analysis (PCA) coefficients of a lung
      motion model. A model that maps the patch intensity to the PCA coefficients was
      built along with the patch selection process. Based on this model, a measured
      projection can be used to predict the PCA coefficients, which are then further
      used to generate a motion vector field and hence a volumetric image. The authors
      have also proposed an intensity baseline correction method based on the
      partitioned projection, in which the first and the second moments of pixel
      intensities at a patch in a simulated projection image are matched with those in
      a measured one via a linear transformation. The proposed method has been
      validated in both simulated data and real phantom data. RESULTS: The algorithm is
      able to identify patches that contain relevant motion information such as the
      diaphragm region. It is found that an intensity baseline correction step is
      important to remove the systematic error in the motion prediction. For the
      simulation case, the sparse learning model reduced the prediction error for the
      first PCA coefficient to 5%, compared to the 10% error when sparse learning was
      not used, and the 95th percentile error for the predicted motion vector was
      reduced from 2.40 to 0.92 mm. In the phantom case with a regular tumor motion,
      the predicted tumor trajectory was successfully reconstructed with a 0.82 mm
      error for tumor center localization compared to a 1.66 mm error without using the
      sparse learning method. When the tumor motion was driven by a real patient
      breathing signal with irregular periods and amplitudes, the average tumor center
      error was 0.6 mm. The algorithm robustness with respect to sparsity level, patch
      size, and presence or absence of diaphragm, as well as computation time, has also
      been studied. CONCLUSIONS: The authors have developed a new method that
      automatically identifies motion information from an x-ray projection, based on
      which a volumetric image is generated.

PMID- 25979045
TI  - A localized Richardson-Lucy algorithm for fiber orientation estimation in high
      angular resolution diffusion imaging.
AB  - PURPOSE: Diffusion tensor imaging is widely used for studying neural fiber
      trajectories in white matter and for quantifying changes in tissue using
      diffusion properties at each voxel in the brain. To better model the nature of
      crossing fibers within complex architectures, rather than using a simplified
      tensor model that assumes only a single fiber direction at each image voxel, a
      model mixing multiple diffusion tensors is used to profile diffusion signals from
      high angular resolution diffusion imaging (HARDI) data. Based on the HARDI signal
      and a multiple tensors model, spherical deconvolution methods have been developed
      to overcome the limitations of the diffusion tensor model when resolving crossing
      fibers. The Richardson-Lucy algorithm is a popular spherical deconvolution method
      used in previous work. However, it is based on a Gaussian distribution, while
      HARDI data are always very noisy, and the distribution of HARDI data follows a
      Rician distribution. This current work aims to present a novel solution to
      address these issues. METHODS: By simultaneously considering both the Rician bias
      and neighbor correlation in HARDI data, the authors propose a localized
      Richardson-Lucy (LRL) algorithm to estimate fiber orientations for HARDI data.
      The proposed method can simultaneously reduce noise and correct the Rician bias.
      RESULTS: Mean angular error (MAE) between the estimated Fiber orientation
      distribution (FOD) field and the reference FOD field was computed to examine
      whether the proposed LRL algorithm offered any advantage over the conventional RL
      algorithm at various levels of noise. Normalized mean squared error (NMSE) was
      also computed to measure the similarity between the true FOD field and the
      estimated FOD filed. For MAE comparisons, the proposed LRL approach obtained the
      best results in most of the cases at different levels of SNR and b-values. For
      NMSE comparisons, the proposed LRL approach obtained the best results in most of
      the cases at b-value = 3000 s/mm(2), which is the recommended schema for HARDI
      data acquisition. In addition, the FOD fields estimated by the proposed LRL
      approach in regions of fiber crossing regions using real data sets also showed
      similar fiber structures which agreed with common acknowledge in these regions.
      CONCLUSIONS: The novel spherical deconvolution method for improved accuracy in
      investigating crossing fibers can simultaneously reduce noise and correct Rician
      bias. With the noise smoothed and bias corrected, this algorithm is especially
      suitable for estimation of fiber orientations in HARDI data. Experimental results
      using both synthetic and real imaging data demonstrated the success and
      effectiveness of the proposed LRL algorithm.

PMID- 25979046
TI  - Real-time markerless lung tumor tracking in fluoroscopic video: Handling
      overlapping of projected structures.
AB  - PURPOSE: Fluoroscopic imaging is a well-suited technique for online visualization
      of tumor motion in the thoracic region. Template-based approaches for tumor
      tracking in such images are commonly used. However, overlapping of different
      structures, mainly bones, can lead to limited visibility of the projected tumor
      shape, which in turn can negatively affect the performance of the tracking
      method. In this study, a method based on multiple-template matching was
      developed, providing fast and robust detection of tumor motion even under the
      influence of occurring tumor overlaps. METHODS: A cohort of 14 patients with
      varying tumor sizes and locations was investigated. Image data from eight of
      these patients were used for evaluation. Based on the requirement of tumor
      visibility, the remaining datasets did not qualify for tracking. Generation of
      multiple templates was improved by implementation of an algorithm for automated
      selection of reference images containing the most characteristic tumor
      appearances. Various measures were taken to ensure real-time capability of the
      algorithm. A prematching step was introduced in order to reduce dispensable
      comparison operations by selecting the most appropriate template. Subsequent
      matching was further optimized by using prior knowledge about likely tumor motion
      to effectively limit necessary matching tasks. RESULTS: Tracking accuracy of the
      developed multiple-template method was compared with that of single-template.
      Mean errors of the multiple-template approach were 0.6 +/- 0.6 mm in left-right
      and 0.9 +/- 0.9 mm in superior-inferior direction in the isocenter plane. The
      single-template approach achieved mean errors of 0.7 +/- 0.7 mm in left-right and
      1.5 +/- 1.3 mm in superior-inferior direction. These results derive from
      evaluation against manual tumor tracking performed by four expert observers.
      Computational times needed for tumor detection in a single fluoroscopic frame
      ranged between 1 and 29 ms depending on the tumor size and motion amplitude.
      CONCLUSIONS: This study shows that in case of tumor overlapping with dense
      structures, multiple-template tracking provides more accurate results than a
      single-template approach. The developed algorithm shows promising results in
      terms of suitability for real-time application and robustness against frequently
      changing overlapping.

PMID- 25979047
TI  - Characterization of a MOSkin detector for in vivo skin dose measurements during
      interventional radiology procedures.
AB  - PURPOSE: The MOSkin is a MOSFET detector designed especially for skin dose
      measurements. This detector has been characterized for various factors affecting
      its response for megavoltage photon beams and has been used for patient dose
      measurements during radiotherapy procedures. However, the characteristics of this
      detector in kilovoltage photon beams and low dose ranges have not been studied.
      The purpose of this study was to characterize the MOSkin detector to determine
      its suitability for in vivo entrance skin dose measurements during interventional
      radiology procedures. METHODS: The calibration and reproducibility of the MOSkin
      detector and its dependency on different radiation beam qualities were carried
      out using RQR standard radiation qualities in free-in-air geometry. Studies of
      the other characterization parameters, such as the dose linearity and dependency
      on exposure angle, field size, frame rate, depth-dose, and source-to-surface
      distance (SSD), were carried out using a solid water phantom under a clinical x
      ray unit. RESULTS: The MOSkin detector showed good reproducibility (94%) and dose
      linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not
      significantly change with the variation of SSD (+/- 1%), field size (+/- 1%),
      frame rate (+/- 3%), or beam energy (+/- 5%). The detector angular dependence was
      within +/- 5% over 360 degrees  and the dose recorded by the MOSkin detector in
      different depths of a solid water phantom was in good agreement with the Markus
      parallel plate ionization chamber to within +/- 3%. CONCLUSIONS: The MOSkin
      detector proved to be reliable when exposed to different field sizes, SSDs,
      depths in solid water, dose rates, frame rates, and radiation incident angles
      within a clinical x-ray beam. The MOSkin detector with water equivalent depth
      equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during
      interventional radiology procedures.

PMID- 25979048
TI  - Cardiac motion correction based on partial angle reconstructed images in x-ray
      CT.
AB  - PURPOSE: Cardiac x-ray CT imaging is still challenging due to heart motion, which
      cannot be ignored even with the current rotation speed of the equipment. In
      response, many algorithms have been developed to compensate remaining motion
      artifacts by estimating the motion using projection data or reconstructed images.
      In these algorithms, accurate motion estimation is critical to the compensated
      image quality. In addition, since the scan range is directly related to the
      radiation dose, it is preferable to minimize the scan range in motion estimation.
      In this paper, the authors propose a novel motion estimation and compensation
      algorithm using a sinogram with a rotation angle of less than 360 degrees . The
      algorithm estimates the motion of the whole heart area using two opposite 3D
      partial angle reconstructed (PAR) images and compensates the motion in the
      reconstruction process. METHODS: A CT system scans the thoracic area including
      the heart over an angular range of 180 degrees  + alpha + beta, where alpha and
      beta denote the detector fan angle and an additional partial angle, respectively.
      The obtained cone-beam projection data are converted into cone-parallel geometry
      via row-wise fan-to-parallel rebinning. Two conjugate 3D PAR images, whose center
      projection angles are separated by 180 degrees , are then reconstructed with an
      angular range of beta, which is considerably smaller than a short scan range of
      180 degrees  + alpha. Although these images include limited view angle artifacts
      that disturb accurate motion estimation, they have considerably better temporal
      resolution than a short scan image. Hence, after preprocessing these artifacts,
      the authors estimate a motion model during a half rotation for a whole field of
      view via nonrigid registration between the images. Finally, motion-compensated
      image reconstruction is performed at a target phase by incorporating the
      estimated motion model. The target phase is selected as that corresponding to a
      view angle that is orthogonal to the center view angles of two conjugate PAR
      images. To evaluate the proposed algorithm, digital XCAT and physical dynamic
      cardiac phantom datasets are used. The XCAT phantom datasets were generated with
      heart rates of 70 and 100 bpm, respectively, by assuming a system rotation time
      of 300 ms. A physical dynamic cardiac phantom was scanned using a slowly rotating
      XCT system so that the effective heart rate will be 70 bpm for a system rotation
      speed of 300 ms. RESULTS: In the XCAT phantom experiment, motion-compensated 3D
      images obtained from the proposed algorithm show coronary arteries with fewer
      motion artifacts for all phases. Moreover, object boundaries contaminated by
      motion are well restored. Even though object positions and boundary shapes are
      still somewhat different from the ground truth in some cases, the authors see
      that visibilities of coronary arteries are improved noticeably and motion
      artifacts are reduced considerably. The physical phantom study also shows that
      the visual quality of motion-compensated images is greatly improved. CONCLUSIONS:
      The authors propose a novel PAR image-based cardiac motion estimation and
      compensation algorithm. The algorithm requires an angular scan range of less than
      360 degrees . The excellent performance of the proposed algorithm is illustrated
      by using digital XCAT and physical dynamic cardiac phantom datasets.

PMID- 25979049
TI  - Measurement of stray radiation within a scanning proton therapy facility: EURADOS
      WG9 intercomparison exercise of active dosimetry systems.
AB  - PURPOSE: To characterize stray radiation around the target volume in scanning
      proton therapy and study the performance of active neutron monitors. METHODS:
      Working Group 9 of the European Radiation Dosimetry Group (EURADOS WG9-Radiation
      protection in medicine) carried out a large measurement campaign at the Trento
      Centro di Protonterapia (Trento, Italy) in order to determine the neutron spectra
      near the patient using two extended-range Bonner sphere spectrometry (BSS)
      systems. In addition, the work focused on acknowledging the performance of
      different commercial active dosimetry systems when measuring neutron ambient dose
      equivalents, H(*)(10), at several positions inside (8 positions) and outside (3
      positions) the treatment room. Detectors included three TEPCs--tissue equivalent
      proportional counters (Hawk type from Far West Technology, Inc.) and six rem
      counters (WENDI-II, LB 6411, RadEyeTM NL, a regular and an extended-range NM2B).
      Meanwhile, the photon component of stray radiation was deduced from the low
      lineal energy transfer part of TEPC spectra or measured using a Thermo
      ScientificTM FH-40G survey meter. Experiments involved a water tank phantom (60 *
      30 * 30 cm(3)) representing the patient that was uniformly irradiated using a 3
      mm spot diameter proton pencil beam with 10 cm modulation width, 19.95 cm distal
      beam range, and 10 * 10 cm(2) field size. RESULTS: Neutron spectrometry around
      the target volume showed two main components at the thermal and fast energy
      ranges. The study also revealed the large dependence of the energy distribution
      of neutrons, and consequently of out-of-field doses, on the primary beam
      direction (directional emission of intranuclear cascade neutrons) and energy
      (spectral composition of secondary neutrons). In addition, neutron mapping within
      the facility was conducted and showed the highest H(*)(10) value of ~ 51 MUSv Gy(
      1); this was measured at 1.15 m along the beam axis. H(*)(10) values
      significantly decreased with distance and angular position with respect to beam
      axis falling below 2 nSv Gy(-1) at the entrance of the maze, at the door outside
      the room and below detection limit in the gantry control room, and at an adjacent
      room (<0.1 nSv Gy(-1)). Finally, the agreement on H(*)(10) values between all
      detectors showed a direct dependence on neutron spectra at the measurement
      position. While conventional rem-counters (LB 6411, RadEyeTM NL, NM2-458)
      underestimated the H(*)(10) by up to a factor of 4, Hawk TEPCs and the WENDI-II
      range-extended detector were found to have good performance (within 20%) even at
      the highest neutron fluence and energy range. Meanwhile, secondary photon dose
      equivalents were found to be up to five times lower than neutrons; remaining
      nonetheless of concern to the patient. CONCLUSIONS: Extended-range BSS, TEPCs,
      and the WENDI-II enable accurate measurements of stray neutrons while other rem
      counters are not appropriate considering the high-energy range of neutrons
      involved in proton therapy.

PMID- 25979050
TI  - An externally and internally deformable, programmable lung motion phantom.
AB  - PURPOSE: Most clinically deployed strategies for respiratory motion management in
      lung radiotherapy (e.g., gating and tracking) use external markers that serve as
      surrogates for tumor motion. However, typical lung phantoms used to validate
      these strategies are based on a rigid exterior and a rigid or a deformable
      interior. Such designs do not adequately represent respiration because the
      thoracic anatomy deforms internally as well as externally. In order to create a
      closer approximation of respiratory motion, the authors describe the construction
      and experimental testing of an externally as well as internally deformable,
      programmable lung phantom. METHODS: The outer shell of a commercially available
      lung phantom (RS-1500, RSD, Inc.) was used. The shell consists of a chest cavity
      with a flexible anterior surface, and embedded vertebrae, rib-cage and sternum. A
      custom-made insert was designed using a piece of natural latex foam block. A
      motion platform was programmed with sinusoidal and ten patient-recorded lung
      tumor trajectories. The platform was used to drive a rigid foam "diaphragm" that
      compressed/decompressed the phantom interior. Experimental characterization
      comprised of determining the reproducibility and the external-internal
      correlation of external and internal marker trajectories extracted from kV x-ray
      fluoroscopy. Experiments were conducted to illustrate three example applications
      of the phantom-(i) validating the geometric accuracy of the VisionRT surface
      photogrammetry system; (ii) validating an image registration tool, NiftyReg; and
      (iii) quantifying the geometric error due to irregular motion in four-dimensional
      computed tomography (4DCT). RESULTS: The phantom correctly reproduced sinusoidal
      and patient-derived motion, as well as realistic respiratory motion-related
      effects such as hysteresis. The reproducibility of marker trajectories over
      multiple runs for sinusoidal as well as patient traces, as characterized by
      fluoroscopy, was within 0.25 mm RMS error. The motion trajectories of internal
      and external radio-opaque markers as measured by fluoroscopy were found to be
      highly correlated (R > 0.95). Using the phantom, it was demonstrated that the
      motion trajectories of regions-of-interest on the surface as measured by VisionRT
      are highly consistent with corresponding fluoroscopically acquired surface marker
      trajectories, with RMS errors within 0.26 mm. Furthermore, it was shown that the
      trajectories of external and internal marker trajectories derived from NiftyReg
      deformation vector fields were within 1 mm root mean square errors comparing to
      trajectories obtained by segmenting markers from individual fluoro frames.
      Finally, it was shown that while 4DCT can be used to localize internal markers
      for sinusoidal motion with reasonable accuracy, the localization error increases
      significantly (by a factor of ~ 2) in the presence of cycle-to-cycle variations
      that are observed in patient-derived respiratory motion. CONCLUSIONS: The authors
      have developed a realistic externally and internally deformable, programmable
      lung phantom that will serve as a valuable tool for clinical and investigational
      motion management studies in thoracic and abdominal radiation therapies.

PMID- 25979051
TI  - Online updating of context-aware landmark detectors for prostate localization in
      daily treatment CT images.
AB  - PURPOSE: In image guided radiation therapy, it is crucial to fast and accurately
      localize the prostate in the daily treatment images. To this end, the authors
      propose an online update scheme for landmark-guided prostate segmentation, which
      can fully exploit valuable patient-specific information contained in the previous
      treatment images and can achieve improved performance in landmark detection and
      prostate segmentation. METHODS: To localize the prostate in the daily treatment
      images, the authors first automatically detect six anatomical landmarks on the
      prostate boundary by adopting a context-aware landmark detection method.
      Specifically, in this method, a two-layer regression forest is trained as a
      detector for each target landmark. Once all the newly detected landmarks from new
      treatment images are reviewed or adjusted (if necessary) by clinicians, they are
      further included into the training pool as new patient-specific information to
      update all the two-layer regression forests for the next treatment day. As more
      and more treatment images of the current patient are acquired, the two-layer
      regression forests can be continually updated by incorporating the patient
      specific information into the training procedure. After all target landmarks are
      detected, a multiatlas random sample consensus (multiatlas RANSAC) method is used
      to segment the entire prostate by fusing multiple previously segmented prostates
      of the current patient after they are aligned to the current treatment image.
      Subsequently, the segmented prostate of the current treatment image is again
      reviewed (or even adjusted if needed) by clinicians before including it as a new
      shape example into the prostate shape dataset for helping localize the entire
      prostate in the next treatment image. RESULTS: The experimental results on 330
      images of 24 patients show the effectiveness of the authors' proposed online
      update scheme in improving the accuracies of both landmark detection and prostate
      segmentation. Besides, compared to the other state-of-the-art prostate
      segmentation methods, the authors' method achieves the best performance.
      CONCLUSIONS: By appropriate use of valuable patient-specific information
      contained in the previous treatment images, the authors' proposed online update
      scheme can obtain satisfactory results for both landmark detection and prostate
      segmentation.

PMID- 25979052
TI  - Investigations into the feasibility of optical-CT 3D dosimetry with minimal use
      of refractively matched fluids.
AB  - PURPOSE: In optical-CT, the use of a refractively matched polyurethane solid-tank
      in place of a fluid bath has the potential to greatly increase practical
      convenience, reduce cost, and possibly improve the efficacy of flood corrections.
      This work investigates the feasibility of solid-tank optical-CT imaging for 3D
      dosimetry through computer simulation. METHODS: A matlab ray-tracing simulation
      platform, ScanSim, was used to model a parallel-source telecentric optical-CT
      imaging system through a polyurethane solid-tank containing a central cylindrical
      hollow into which PRESAGE radiochromic dosimeters can be placed. A small amount
      of fluid fills the 1-5 mm gap between the dosimeter and the walls of the tank.
      The use of the solid-tank reduces the required amount of fluid by approximately
      97%. To characterize the efficacy of solid-tank, optical-CT scanning simulations
      investigated sensitivity to refractive index (RI) mismatches between dosimeter,
      solid-tank, and fluid, for a variety of dosimeter (RI = 1.5-1.47) and fluid (RI =
      1.55-1.0) combinations. Efficacy was evaluated through the usable radius (ru)
      metric, defined as the fraction of the radius of the dosimeter where measured
      dose is predicted to be within 2% of the ground truth entered into the
      simulation. Additional simulations examined the effect of increasing gap size (1
      5 mm) between the dosimeter and solid-tank well. The effects of changing the lens
      tolerance (0.5 degrees -5.0 degrees ) were also investigated. RESULTS: As the RI
      mismatch between the dosimeter and solid-tank increased from 0 to 0.02, the
      usable radius decreased from 97.6% to 50.2%. The optimal fluid RI decreased
      nonlinearly from 1.5 to 1.34 as the mismatch increased and was up to 9% lower
      than the tank. Media mismatches between the dosimeter and solid-tank also
      exacerbate the effects of changing the gap size, with no easily quantifiable
      relationship with usable radius. Generally, the optimal fluid RI value increases
      as gap size increases and is closely matched to the dosimeter at large gap sizes
      (> 3 mm). Increasing the telecentric lens tolerance increases the usable radius
      for all refractive media combinations and improves the maximum usable radius of
      mismatched media to that of perfectly matched media for tolerances > 5.0 degrees
      . The maximum usable radius can be improved up to a factor of 2 when lens
      tolerances are small (< 1.0 degrees ). CONCLUSIONS: Dry solid-tank optical-CT
      imaging in a telecentric system is feasible if the dosimeter RI is a close match
      with the solid-tank (< 0.01 difference), providing accurate dose measurements
      within +/- 2% of true dose to over 80% of the dosimeter volume. In order to
      achieve accurate measurements over 96% of the dosimeter volume (representing out
      to 2 mm from the dosimeter edge), the dosimeter-tank RI mismatch must be less
      than 0.005. Optimal results occur when the RI of the dosimeter and tank is the
      same, in which case the fluid will have the same RI. If mismatches between the
      tank and dosimeter RI occur, the RI of the matching fluid needs to be fine tuned
      to achieve the highest usable radius.

PMID- 25979053
TI  - Treatment planning for radiotherapy with very high-energy electron beams and
      comparison of VHEE and VMAT plans.
AB  - PURPOSE: The aim of this work was to develop a treatment planning workflow for
      rapid radiotherapy delivered with very high-energy electron (VHEE) scanning
      pencil beams of 60-120 MeV and to study VHEE plans as a function of VHEE
      treatment parameters. Additionally, VHEE plans were compared to clinical state-of
      the-art volumetric modulated arc therapy (VMAT) photon plans for three cases.
      METHODS: VHEE radiotherapy treatment planning was performed by linking EGSnrc
      Monte Carlo (MC) dose calculations with inverse treatment planning in a research
      version of RayStation. In order to study the effect of VHEE treatment parameters
      on VHEE dose distributions, a matlab graphical user interface (GUI) for
      calculation of VHEE MC pencil beam doses was developed. Through the GUI,
      pediatric case MC simulations were run for a number of beam energies (60, 80,
      100, and 120 MeV), number of beams (13, 17, and 36), pencil beam spot (0.1, 1.0,
      and 3.0 mm) and grid (2.0, 2.5, and 3.5 mm) sizes, and source-to-axis distance,
      SAD (40 and 50 cm). VHEE plans for the pediatric case calculated with the
      different treatment parameters were optimized and compared. Furthermore, 100 MeV
      VHEE plans for the pediatric case, a lung, and a prostate case were calculated
      and compared to the clinically delivered VMAT plans. All plans were normalized
      such that the 100% isodose line covered 95% of the target volume. RESULTS: VHEE
      beam energy had the largest effect on the quality of dose distributions of the
      pediatric case. For the same target dose, the mean doses to organs at risk (OARs)
      decreased by 5%-16% when planned with 100 MeV compared to 60 MeV, but there was
      no further improvement in the 120 MeV plan. VHEE plans calculated with 36 beams
      outperformed plans calculated with 13 and 17 beams, but to a more modest degree
      (<8%). While pencil beam spacing and SAD had a small effect on VHEE dose
      distributions, 0.1-3 mm pencil beam sizes resulted in identical dose
      distributions. For the 100 MeV VHEE pediatric plan, OAR doses were up to 70%
      lower and the integral dose was 33% lower for VHEE compared to 6 MV VMAT.
      Additionally, VHEE conformity indices (CI100 = 1.09 and CI50 = 4.07) were better
      than VMAT conformity indices (CI100 = 1.30 and CI50 = 6.81). The 100 MeV VHEE
      lung plan resulted in mean dose decrease to all OARs by up to 27% for the same
      target coverage compared to the clinical 6 MV flattening filter-free (FFF) VMAT
      plan. The 100 MeV prostate plan resulted in 3% mean dose increase to the penile
      bulb and the urethra, but all other OAR mean doses were lower compared to the 15
      MV VMAT plan. The lung case CI100 and CI50 conformity indices were 3% and 8%
      lower, respectively, in the VHEE plan compared to the VMAT plan. The prostate
      case CI100 and CI50 conformity indices were 1% higher and 8% lower, respectively,
      in the VHEE plan compared to the VMAT plan. CONCLUSIONS: The authors have
      developed a treatment planning workflow for MC dose calculation of pencil beams
      and optimization for treatment planning of VHEE radiotherapy. The authors have
      demonstrated that VHEE plans resulted in similar or superior dose distributions
      for pediatric, lung, and prostate cases compared to clinical VMAT plans.

PMID- 25979054
TI  - Preclinical investigation for developing injectable fiducial markers using a
      mixture of BaSO4 and biodegradable polymer for proton therapy.
AB  - PURPOSE: The aim of this study is to investigate the use of mixture of BaSO4 and
      biodegradable polymer as an injectable nonmetallic fiducial marker to reduce
      artifacts in x-ray images, decrease the absorbed dose distortion in proton
      therapy, and replace permanent metal markers. METHODS: Two samples were made with
      90 wt. % polymer phosphate buffer saline (PBS) and 10 wt. % BaSO4 (B1) or 20 wt.
      % BaSO4 (B2). Two animal models (mice and rats) were used. To test the
      injectability and in vivo gelation, a volume of 200 MUl at a pH 5.8 were injected
      into the Sprague-Dawley rats. After sacrificing the rats over time, the authors
      checked the gel morphology. Detectability of the markers in the x-ray images was
      tested for two sizes (diameters of 1 and 2 mm) for B1 and B2. Four samples were
      injected into BALB/C mice. The polymer mixed with BaSO4 transform from SOL at 20 
      degrees C with a pH of 6.0 to GEL in the living body at 37  degrees C with a pH
      of 7.4, so the size of the fiducial marker could be controlled by adjusting the
      injected volume. The detectability of the BaSO4 marker was measured in x-ray
      images of cone beam CT (CBCT), on-board imager [anterior-posterior (AP),
      lateral], and fluoroscopy (AP, lateral) using a Novalis-TX (Varian Medical
      Systems, Palo Alto, CA) repeatedly over 4 months. The volume, HU, and artifacts
      for the markers were measured in the CBCT images. Artifacts were compared to
      those of gold marker by analyzing the HU distribution. The dose distortion in
      proton therapy was computed by using a Monte Carlo (MC) code. A cylindrical
      shaped marker (diameter: 1 or 2 mm, length: 3 mm) made of gold, stainless-steel
      [304], titanium, and 20 wt. % BaSO4 was positioned at the center of the spread
      out Bragg peak (SOBP) in parallel or perpendicular to the beam entrance. The dose
      distortion was measured on the depth dose profile across the markers. RESULTS:
      Transformation to GEL and the biodegradation were verified. All BaSO4 markers
      could be detected in the CBCT. In the OBI and fluoroscopy images, all markers
      visible in the AP, but only B2(2 mm) could be identified in the lateral images.
      Changes of BaSO4 position were not detected in vivo (mice). The volume of the
      markers decreased by up to 65% and the HU increased by 22%, on average. The mean
      HU values around the B1, B2, and gold markers were 121.30 [standard deviation
      (SD): 54.86], 126.31 (SD: 62.13), and 1070.7 (SD: 235.16), respectively. The MC
      simulated dose distortion for the BaSO4 markers was less than that of the
      commercially used markers. The dose reduction due to the gold marker was largest
      (15.05%) followed by stainless steel (7.92%) and titanium (6.92%). Dose reduction
      by B2 (2 mm) was 4.75% and 0.53% in parallel and perpendicular orientations,
      respectively. CONCLUSIONS: BaSO4 mixed with PBS is a good contrast agent in
      biodegradable polymer marker because of minimal artifacts in x-ray images and
      minimal dose reduction in proton therapy. The flexibility of the size is
      considered to be an advantage of this material over solid type fiducials.

PMID- 25979056
TI  - Comment on "Monte Carlo evaluations of the absorbed dose and quality dependence
      of Al2O3 in radiotherapy photon beams" [Med. Phys. 36(10), 4421-4424 (2009)].

PMID- 25979055
TI  - Visibility and artifacts of gold fiducial markers used for image guided radiation
      therapy of pancreatic cancer on MRI.
AB  - PURPOSE: In radiation therapy of pancreatic cancer, tumor alignment prior to each
      treatment fraction is improved when intratumoral gold fiducial markers (from here
      onwards: markers), which are visible on computed tomography (CT) and cone beam
      CT, are used. Visibility of these markers on magnetic resonance imaging (MRI)
      might improve image registration between CT and magnetic resonance (MR) images
      for tumor delineation purposes. However, concomitant image artifacts induced by
      markers are undesirable. The extent of visibility and artifact size depend on MRI
      sequence parameters. The authors' goal was to determine for various markers their
      potential to be visible and to generate artifacts, using measures that are
      independent of the MRI-sequence parameters. METHODS: The authors selected ten
      different markers suitable for endoscopic placement in the pancreas and placed
      them into a phantom. The markers varied in diameter (0.28-0.6 mm), shape, and
      iron content (0%-0.5%). For each marker, the authors calculated T2 (*)-maps and
      DeltaB0-maps using MRI measurements. A decrease in relaxation time T2 (*) can
      cause signal voids, associated with visibility, while a change in the magnetic
      field B0 can cause signal shifts, which are associated with artifacts. These
      shifts inhibit accurate tumor delineation. As a measure for potential visibility,
      the authors used the volume of low T2 (*), i.e., the volume for which T2 (*)
      differed from the background by >15 ms. As a measure for potential artifacts, the
      authors used the volume for which |DeltaB0| > 9.4 * 10(-8) T (4 Hz). To test
      whether there is a correlation between visibility and artifact size, the authors
      calculated the Spearman's correlation coefficient (Rs) between the volume of low
      T2 (*) and the volume of high |DeltaB0|. The authors compared the maps with
      images obtained using a clinical MR-sequence. Finally, for the best visible
      marker as well as the marker that showed the smallest artifact, the authors
      compared the phantom data with in vivo MR-images in four pancreatic cancer
      patients. RESULTS: The authors found a strong correlation (Rs = 1.00, p < 0.01)
      between the volume of low T2 (*) and the volume with high |DeltaB0|. Visibility
      in clinical MR-images increased with lower T2 (*). Signal shift artifacts became
      worse for markers with high |DeltaB0|. The marker that was best visible in the
      phantom, a folded marker with 0.5% iron content, was also visible in vivo, but
      showed artifacts on diffusion weighted images. The marker with the smallest
      artifact in the phantom, a small, stretched, ironless marker, was indiscernible
      on in vivo MR-images. CONCLUSIONS: Changes in T2 (*) and DeltaB0 are sequence
      independent measures for potential visibility and artifact size, respectively.
      Improved visibility of markers correlates strongly to signal shift artifacts;
      therefore, marker choice will depend on the clinical purpose. When visibility of
      the markers is most important, markers that contain iron are optimal, preferably
      in a folded configuration. For artifact sensitive imaging, small ironless markers
      are best, preferably in a stretched configuration.

PMID- 25979057
TI  - Response to "Comment on 'Monte Carlo evaluations of the absorbed dose and quality
      dependence of Al2O3 in radiotherapy photon beams' " [Med. Phys. 36, 4421-4424
      (2009)].

PMID- 25979058
TI  - Erratum: "Predicting adenocarcinoma recurrence using computational texture models
      of nodule components in lung CT" [Med. Phys. 42, 2054 (10pp.) (2015)].

PMID- 25979059
TI  - Erratum: "Phase-based x-ray scattering--A possible method to detect cancer cells
      in a very early stage" [Med. Phys. 41(5), 053503 (12pp.) (2014)].

PMID- 25979061
TI  - Introduction: Advances and trends in image formation in X-ray computed
      tomography.

PMID- 25979062
TI  - Editor's Note: "Creation of an atlas of filter positions for fluence field
      modulated CT" [Med. Phys. 42, 1779 (2015)].

PMID- 25979063
TI  - Editor's Note: "Patient-bounded extrapolation using low-dose priors for volume-of
      interest imaging in C-arm CT" [Med. Phys. 42, 1787 (2015)].

PMID- 25979064
TI  - A new redundancy weighting scheme for nonstationary data for computed tomography.
AB  - PURPOSE: The same projection data (or line integrals) are often measured multiple
      times, e.g., twice from opposite directions during one gantry rotation. The
      redundant data must be normalized by applying redundancy weighting such as the
      halfscan algorithm, which assumes that the noise of the data is uniform. This
      assumption, however, is not correct when a tube current modulation technique is
      employed. The variance of line integrals, which is inversely related to the tube
      current, could vary significantly. The purpose of this work is to improve how the
      projection data are used during analytical reconstruction when the tube current
      is modulated during the scan. METHODS: The authors developed a new redundancy
      weighting scheme. It not only takes into account the data statistics but also can
      control how much to weigh the statistics from 100% (alphas = 1.0) to 0% (alphas =
      0.0) by a parameter alphas. The proposed weighting scheme reduces to the
      conventional redundancy weighting scheme when alphas = 0.0. The authors evaluated
      the performance of the proposed scheme using computer simulations targeting at
      myocardial perfusion CT imaging. The image quality was evaluated in terms of the
      image noise and halfscan artifacts, and perfusion defect detection performance
      was evaluated by the positive predictive value (PPV) and the area-under-the
      receiver operating characteristic-curve (AUC) value. RESULTS: Results showed a
      tradeoff between the image noise and halfscan artifacts. The normalized noise
      standard deviation was 1.00 with halfscan, 0.89 with alphas = 1.0, 0.97 with
      alphas = 0.5, and 1.20 with alphas = 0.0 when projections over one rotation (75%
      of projections are acquired with full dose, 25% with 1/10 of the full dose) are
      used. The halfscan artifacts were 13.4 Hounsfield unit (HU) with halfscan, 8.2 HU
      with alphas = 1.0, 4.5 HU with alphas = 0.5, and 3.1 HU with alphas = 0.0. Both
      the PPVs and AUCs were improved from the halfscan method: PPV, 69.0%-70.6% vs
      58.0%, P < 0.003; AUC, 0.935-0.938 vs 0.908, P < 0.003. CONCLUSIONS: The new
      redundancy weight allows for decreasing the image noise and controlling the
      tradeoff between the image noise and artifacts.

PMID- 25979065
TI  - New CT system architectures for high temporal resolution with applications to
      improved geometric dose efficiency and cardiac imaging.
AB  - PURPOSE: A new scalable computed tomography (CT) system architecture is
      introduced with the potential to achieve much higher temporal resolution than is
      possible with current CT designs while maintaining the flux per imaged slice near
      today's levels. The concept relies only on known technologies; in particular,
      effective rotation speeds several times higher than what is possible today can be
      achieved leveraging today's x-ray tube designs and capabilities. METHODS: The new
      CT architecture comprises the following elements: (1) decoupling of the source
      rotation from the detector rotation through the provision of two independent,
      coaxial and coplanar rotating gantries (drums), (2) observation of a source at a
      range of azimuthal angles with respect to a given detector cell, (3) utilization
      of a multiplicity of x-ray sources, (4) use of a wide-angle isocentered detector
      mounted on the independent detector drum, (5) the detector drum presents a wide
      angular aperture allowing x-rays from the various sources to pass through, with
      the active detector cells occupying about 240 degrees  in one configuration, and
      the wide aperture the complementary 120 degrees , (6) antiscatter grids with
      absorbing lamellas oriented substantially parallel to the main gantry plane, and
      (7) optional sparse view acquisition in "bunches," a sparse sampling pattern
      potentially enabling further data-acquisition speedup for specific applications.
      Temporal resolution gains are achieved when K multiple sources are simultaneously
      in view of the extended detector. Accordingly, projection data relate to the sum
      of up to K line-integral terms; recovery of the individual line-integral
      estimates that form the input to the usual image reconstruction methods
      necessitates the inversion of a sparse linear system. When data for a tomographic
      slice are acquired during a full effective gantry rotation, the linear system is
      amenable to inversion; when high temporal resolution is sought, the system is
      underdetermined and a-priori information is useful in regularizing the problem. A
      regularization method is proposed whereby each sampling time interval is
      subdivided and individual projection data are acquired for each source during a
      subinterval. Other approaches involve spectral multiplexing. Thus, the use of an
      energy-discriminating detector such as a photon-counting detector will be
      advantageous to the proposed design. Recently developed volume-based scatter
      correction methods have the potential to apply to the proposed architectures.
      RESULTS: Mathematical modeling indicates acquisition of complete data for a given
      transaxial slice could be achieved in 50 ms or less, while delivering an x-ray
      exposure commensurate with that delivered by a system acquiring complete data in
      200 ms. Applications include cardiac CT and the design of a CT system with nearly
      100% geometric dose efficiency, whereby the effective rotation speed enables the
      use of a relatively narrow z-aperture detector, with no antiscatter grids. This
      represents a 33% dose reduction versus a system with 75% geometric dose
      efficiency. CONCLUSIONS: A new, scalable CT system architecture has been
      described that can potentially lead to large increases in temporal resolution.
      Potential applications include cardiac CT and the design of a system with 100%
      dose geometric dose efficiency. Future investigations will address the
      feasibility of the proposed approach.

PMID- 25979066
TI  - Variability in CT lung-nodule volumetry: Effects of dose reduction and
      reconstruction methods.
AB  - PURPOSE: Measuring the size of nodules on chest CT is important for lung cancer
      staging and measuring therapy response. 3D volumetry has been proposed as a more
      robust alternative to 1D and 2D sizing methods. There have also been substantial
      advances in methods to reduce radiation dose in CT. The purpose of this work was
      to investigate the effect of dose reduction and reconstruction methods on
      variability in 3D lung-nodule volumetry. METHODS: Reduced-dose CT scans were
      simulated by applying a noise-addition tool to the raw (sinogram) data from
      clinically indicated patient scans acquired on a multidetector-row CT scanner
      (Definition Flash, Siemens Healthcare). Scans were simulated at 25%, 10%, and 3%
      of the dose of their clinical protocol (CTDIvol of 20.9 mGy), corresponding to
      CTDIvol values of 5.2, 2.1, and 0.6 mGy. Simulated reduced-dose data were
      reconstructed with both conventional filtered backprojection (B45 kernel) and
      iterative reconstruction methods (SAFIRE: I44 strength 3 and I50 strength 3).
      Three lab technologist readers contoured "measurable" nodules in 33 patients
      under each of the different acquisition/reconstruction conditions in a blinded
      study design. Of the 33 measurable nodules, 17 were used to estimate
      repeatability with their clinical reference protocol, as well as interdose and
      inter-reconstruction-method reproducibilities. The authors compared the resulting
      distributions of proportional differences across dose and reconstruction methods
      by analyzing their means, standard deviations (SDs), and t-test and F-test
      results. RESULTS: The clinical-dose repeatability experiment yielded a mean
      proportional difference of 1.1% and SD of 5.5%. The interdose reproducibility
      experiments gave mean differences ranging from -5.6% to -1.7% and SDs ranging
      from 6.3% to 9.9%. The inter-reconstruction-method reproducibility experiments
      gave mean differences of 2.0% (I44 strength 3) and -0.3% (I50 strength 3), and
      SDs were identical at 7.3%. For the subset of repeatability cases, inter
      reconstruction-method mean/SD pairs were (1.4%, 6.3%) and (-0.7%, 7.2%) for I44
      strength 3 and I50 strength 3, respectively. Analysis of representative nodules
      confirmed that reader variability appeared unaffected by dose or reconstruction
      method. CONCLUSIONS: Lung-nodule volumetry was extremely robust to the radiation
      dose level, down to the minimum scanner-supported dose settings. In addition,
      volumetry was robust to the reconstruction methods used in this study, which
      included both conventional filtered backprojection and iterative methods.

PMID- 25979067
TI  - Noise properties of CT images reconstructed by use of constrained total
      variation, data-discrepancy minimization.
AB  - PURPOSE: The authors develop and investigate iterative image reconstruction
      algorithms based on data-discrepancy minimization with a total-variation (TV)
      constraint. The various algorithms are derived with different data-discrepancy
      measures reflecting the maximum likelihood (ML) principle. Simulations
      demonstrate the iterative algorithms and the resulting image statistical
      properties for low-dose CT data acquired with sparse projection view angle
      sampling. Of particular interest is to quantify improvement of image statistical
      properties by use of the ML data fidelity term. METHODS: An incremental algorithm
      framework is developed for this purpose. The instances of the incremental
      algorithms are derived for solving optimization problems including a data
      fidelity objective function combined with a constraint on the image TV. For the
      data fidelity term the authors, compare application of the maximum likelihood
      principle, in the form of weighted least-squares (WLSQ) and Poisson-likelihood
      (PL), with the use of unweighted least-squares (LSQ). RESULTS: The incremental
      algorithms are applied to projection data generated by a simulation modeling the
      breast computed tomography (bCT) imaging application. The only source of data
      inconsistency in the bCT projections is due to noise, and a Poisson distribution
      is assumed for the transmitted x-ray photon intensity. In the simulations
      involving the incremental algorithms an ensemble of images, reconstructed from
      1000 noise realizations of the x-ray transmission data, is used to estimate the
      image statistical properties. The WLSQ and PL incremental algorithms are seen to
      reduce image variance as compared to that of LSQ without sacrificing image bias.
      The difference is also seen at few iterations--short of numerical convergence of
      the corresponding optimization problems. CONCLUSIONS: The proposed incremental
      algorithms prove effective and efficient for iterative image reconstruction in
      low-dose CT applications particularly with sparse-view projection data.

PMID- 25979068
TI  - Accelerated statistical reconstruction for C-arm cone-beam CT using Nesterov's
      method.
AB  - PURPOSE: To accelerate model-based iterative reconstruction (IR) methods for C
      arm cone-beam CT (CBCT), thereby combining the benefits of improved image quality
      and/or reduced radiation dose with reconstruction times on the order of minutes
      rather than hours. METHODS: The ordered-subsets, separable quadratic surrogates
      (OS-SQS) algorithm for solving the penalized-likelihood (PL) objective was
      modified to include Nesterov's method, which utilizes "momentum" from image
      updates of previous iterations to better inform the current iteration and provide
      significantly faster convergence. Reconstruction performance of an
      anthropomorphic head phantom was assessed on a benchtop CBCT system, followed by
      CBCT on a mobile C-arm, which provided typical levels of incomplete data,
      including lateral truncation. Additionally, a cadaveric torso that presented
      realistic soft-tissue and bony anatomy was imaged on the C-arm, and different
      projectors were assessed for reconstruction speed. RESULTS: Nesterov's method
      provided equivalent image quality to OS-SQS while reducing the reconstruction
      time by an order of magnitude (10.0 *) by reducing the number of iterations
      required for convergence. The faster projectors were shown to produce similar
      levels of convergence as more accurate projectors and reduced the reconstruction
      time by another 5.3 *. Despite the slower convergence of IR with truncated C-arm
      CBCT, comparison of PL reconstruction methods implemented on graphics processing
      units showed that reconstruction time was reduced from 106 min for the
      conventional OS-SQS method to as little as 2.0 min with Nesterov's method for a
      volumetric reconstruction of the head. In body imaging, reconstruction of the
      larger cadaveric torso was reduced from 159 min down to 3.3 min with Nesterov's
      method. CONCLUSIONS: The acceleration achieved through Nesterov's method combined
      with ordered subsets reduced IR times down to a few minutes. This improved
      compatibility with clinical workflow better enables broader adoption of IR in
      CBCT-guided procedures, with corresponding benefits in overcoming conventional
      limits of image quality at lower dose.

PMID- 25979069
TI  - Modeling blurring effects due to continuous gantry rotation: Application to
      region of interest tomography.
AB  - PURPOSE: Projections acquired with continuous gantry rotation may suffer from
      blurring effects, depending on the rotation speed and the exposure time of each
      projection. This leads to blurred reconstructions if conventional reconstruction
      algorithms are applied. In this paper, the authors propose a reconstruction
      method for fast acquisitions based on a continuously moving and continuously
      emitting x-ray source. They study the trade-off between total acquisition time
      and reconstruction quality and compare with conventional reconstructions using
      projections acquired with a stepwise moving x-ray source. METHODS: The authors
      introduce the algebraic reconstruction technique with angular integration
      concept, which models the angular integration due to the relative motion of the x
      ray source during the projection. RESULTS: Compared to conventional
      reconstruction from projections acquired with pulsed x-ray emission, the proposed
      method results in substantially improved reconstruction quality around the center
      of rotation. Outside this region, the proposed method results in improved radial
      resolution and a decreased tangential resolution. For a fixed reconstruction
      quality of this region of interest, the proposed method enables a lower number of
      projections and thus a faster acquisition. CONCLUSIONS: The modeling of the
      continuous gantry rotation in the proposed method substantially improves the
      reconstruction quality in a region of interest around the rotation center. The
      proposed method shows potential for fast region of interest tomography.

PMID- 25979070
TI  - Dynamic detector offsets for field of view extension in C-arm computed tomography
      with application to weight-bearing imaging.
AB  - PURPOSE: In C-arm computed tomography (CT), the field of view (FOV) is often not
      sufficient to acquire certain anatomical structures, e.g., a full hip or thorax.
      Proposed methods to extend the FOV use a fixed detector displacement and a 360
      degrees  scan range to double the radius of the FOV. These trajectories are
      designed for circular FOVs. However, there are cases in which the required FOV is
      not circular but rather an ellipsoid. METHODS: In this work, the authors show
      that in fan-beam CT, the use of a dynamically adjusting detector offset can
      reduce the required scan range when using a noncircular FOV. Furthermore, the
      authors present an analytic solution to determine the minimal required scan
      ranges for elliptic FOVs given a certain detector size and an algorithmic
      approach for arbitrary FOVs. RESULTS: The authors show that the proposed method
      can result in a substantial reduction of the required scan range. Initial
      reconstructions of data sets acquired with our new minimal trajectory yielded
      image quality comparable to reconstructions of data acquired using a fixed
      detector offset and a full 360 degrees  rotation. CONCLUSIONS: Our results show a
      promising reduction of the necessary scan range especially for ellipsoidal
      objects that extend the FOV. In noncircular FOVs, there exists a set of solutions
      that allow a trade-off between detector size and scan range.

PMID- 25979071
TI  - Acquisition, preprocessing, and reconstruction of ultralow dose volumetric CT
      scout for organ-based CT scan planning.
AB  - PURPOSE: Traditionally, 2D radiographic preparatory scan images (scout scans) are
      used to plan diagnostic CT scans. However, a 3D CT volume with a full 3D organ
      segmentation map could provide superior information for customized scan planning
      and other purposes. A practical challenge is to design the volumetric scout
      acquisition and processing steps to provide good image quality (at least good
      enough to enable 3D organ segmentation) while delivering a radiation dose similar
      to that of the conventional 2D scout. METHODS: The authors explored various
      acquisition methods, scan parameters, postprocessing methods, and reconstruction
      methods through simulation and cadaver data studies to achieve an ultralow dose
      3D scout while simultaneously reducing the noise and maintaining the edge
      strength around the target organ. RESULTS: In a simulation study, the 3D scout
      with the proposed acquisition, preprocessing, and reconstruction strategy
      provided a similar level of organ segmentation capability as a traditional 240
      mAs diagnostic scan, based on noise and normalized edge strength metrics. At the
      same time, the proposed approach delivers only 1.25% of the dose of a traditional
      scan. In a cadaver study, the authors' pictorial-structures based organ
      localization algorithm successfully located the major abdominal-thoracic organs
      from the ultralow dose 3D scout obtained with the proposed strategy. CONCLUSIONS:
      The authors demonstrated that images with a similar degree of segmentation
      capability (interpretability) as conventional dose CT scans can be achieved with
      an ultralow dose 3D scout acquisition and suitable postprocessing. Furthermore,
      the authors applied these techniques to real cadaver CT scans with a CTDI dose
      level of less than 0.1 mGy and successfully generated a 3D organ localization
      map.

PMID- 25979072
TI  - Dose reconstruction for real-time patient-specific dose estimation in CT.
AB  - PURPOSE: Many recent computed tomography (CT) dose reduction approaches belong to
      one of three categories: statistical reconstruction algorithms, efficient x-ray
      detectors, and optimized CT acquisition schemes with precise control over the x
      ray distribution. The latter category could greatly benefit from fast and
      accurate methods for dose estimation, which would enable real-time patient
      specific protocol optimization. METHODS: The authors present a new method for
      volumetrically reconstructing absorbed dose on a per-voxel basis, directly from
      the actual CT images. The authors' specific implementation combines a distance
      driven pencil-beam approach to model the first-order x-ray interactions with a
      set of Gaussian convolution kernels to model the higher-order x-ray interactions.
      The authors performed a number of 3D simulation experiments comparing the
      proposed method to a Monte Carlo based ground truth. RESULTS: The authors'
      results indicate that the proposed approach offers a good trade-off between
      accuracy and computational efficiency. The images show a good qualitative
      correspondence to Monte Carlo estimates. Preliminary quantitative results show
      errors below 10%, except in bone regions, where the authors see a bigger model
      mismatch. The computational complexity is similar to that of a low-resolution
      filtered-backprojection algorithm. CONCLUSIONS: The authors present a method for
      analytic dose reconstruction in CT, similar to the techniques used in radiation
      therapy planning with megavoltage energies. Future work will include refinements
      of the proposed method to improve the accuracy as well as a more extensive
      validation study. The proposed method is not intended to replace methods that
      track individual x-ray photons, but the authors expect that it may prove useful
      in applications where real-time patient-specific dose estimation is required.

PMID- 25979074
TI  - Ghrelin Inhibition Restores Glucose Homeostasis in Hepatocyte Nuclear Factor
      1alpha (MODY3)-Deficient Mice.
AB  - Hepatocyte nuclear factor-1alpha (HNF1alpha) is a transcription factor expressed
      in tissues of endoderm origin. Mutations in HNF1A are associated with maturity
      onset diabetes of the young 3 (MODY3). Mice deficient for Hnf1alpha are
      hyperglycemic, with their pancreatic beta-cells being defective in glucose
      sensing insulin secretion. The specific mechanisms involved in this defect are
      unclear. Gut hormones control glucose homeostasis. Our objective was to explore
      whether changes in these hormones play a role in glucose homeostasis in the
      absence of Hnf1alpha. An increase in ghrelin gene transcript and a decrease in
      glucose-dependent insulinotropic polypeptide (GIP) gene transcripts were observed
      in the gut of Hnf1alpha-null mice. These changes correlated with an increase of
      ghrelin and a decrease of GIP-labeled cells. Ghrelin serological levels were
      significantly induced in Hnf1alpha-null mice. Paradoxically, GIP levels were also
      induced in these mice. Treatment of Hnf1alpha-null mice with a ghrelin antagonist
      led to a recovery of the diabetic symptoms. We conclude that upregulation of
      ghrelin in the absence of Hnf1alpha impairs insulin secretion and can be reversed
      by pharmacological inhibition of ghrelin/GHS-R interaction. These observations
      open up on future strategies to counteract ghrelin action in a program that could
      become beneficial in controlling non-insulin-dependent diabetes. 

PMID- 25979073
TI  - Plasma Kallikrein-Kinin System as a VEGF-Independent Mediator of Diabetic Macular
      Edema.
AB  - This study characterizes the kallikrein-kinin system in vitreous from individuals
      with diabetic macular edema (DME) and examines mechanisms contributing to retinal
      thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK)
      and plasma kallikrein (PKal) were increased twofold and 11.0-fold (both P <
      0.0001), respectively, in vitreous from subjects with DME compared with those
      with a macular hole (MH). While the vascular endothelial growth factor (VEGF)
      level was also increased in DME vitreous, PKal and VEGF concentrations do not
      correlate (r = 0.266, P = 0.112). Using mass spectrometry-based proteomics, we
      identified 167 vitreous proteins, including 30 that were increased in DME
      (fourfold or more, P < 0.001 vs. MH). The majority of proteins associated with
      DME displayed a higher correlation with PPK than with VEGF concentrations. DME
      vitreous containing relatively high levels of PKal and low VEGF induced RVP when
      injected into the vitreous of diabetic rats, a response blocked by bradykinin
      receptor antagonism but not by bevacizumab. Bradykinin-induced retinal thickening
      in mice was not affected by blockade of VEGF receptor 2. Diabetes-induced RVP was
      decreased by up to 78% (P < 0.001) in Klkb1 (PPK)-deficient mice compared with
      wild-type controls. B2- and B1 receptor-induced RVP in diabetic mice was blocked
      by endothelial nitric oxide synthase (NOS) and inducible NOS deficiency,
      respectively. These findings implicate the PKal pathway as a VEGF-independent
      mediator of DME. 

PMID- 25979075
TI  - The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type
      2 Diabetes.
AB  - To define the components of the metabolic syndrome that contribute to diabetic
      polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db
      mouse, an established murine model of T2DM and the metabolic syndrome, with the
      thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db
      mice produced a significant weight gain, restored glycemic control, and
      normalized measures of serum oxidative stress and triglycerides but had no effect
      on LDLs or total cholesterol. Moreover, although pioglitazone treatment
      normalized renal function, it had no effect on measures of large myelinated nerve
      fibers, specifically sural or sciatic nerve conduction velocities, but
      significantly improved measures of small unmyelinated nerve fiber architecture
      and function. Analyses of gene expression arrays of large myelinated sciatic
      nerves from pioglitazone-treated animals revealed an unanticipated increase in
      genes related to adipogenesis, adipokine signaling, and lipoprotein signaling,
      which likely contributed to the blunted therapeutic response. Similar analyses of
      dorsal root ganglion neurons revealed a salutary effect of pioglitazone on
      pathways related to defense and cytokine production. These data suggest
      differential susceptibility of small and large nerve fibers to specific metabolic
      impairments associated with T2DM and provide the basis for discussion of new
      treatment paradigms for individuals with T2DM and DPN. 

PMID- 25979076
TI  - Continuous mucociliary transport by primary human airway epithelial cells in
      vitro.
AB  - Mucociliary clearance (MCC) is an important innate defense mechanism that
      continuously removes inhaled pathogens and particulates from the airways. Normal
      MCC is essential for maintaining a healthy respiratory system, and impaired MCC
      is a feature of many airway diseases, including both genetic (cystic fibrosis,
      primary ciliary dyskinesia) and acquired (chronic obstructive pulmonary disease,
      bronchiectasis) disorders. Research into the fundamental processes controlling
      MCC, therefore, has direct clinical application, but has been limited in part due
      to the difficulty of studying this complex multicomponent system in vitro. In
      this study, we have characterized a novel method that allows human airway
      epithelial cells to differentiate into a mucociliary epithelium that transports
      mucus in a continuous circular track. The mucociliary transport device allows the
      measurement and manipulation of all features of mucociliary transport in a
      controlled in vitro system. In this initial study, the effect of ciliary beat
      frequency and mucus concentration on the speed of mucociliary transport was
      investigated. 

PMID- 25979077
TI  - Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in
      heaves, an asthma-like disease of horses.
AB  - Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway
      smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription
      factor that regulates myocyte differentiation in vitro in vascular and intestinal
      smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes
      ASM proliferation while binding to myocardin (MYOCD) leading to the expression of
      contractile elements in these tissues. The objective of this study was therefore
      to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from
      central and peripheral airways in heaves, a spontaneously occurring asthma-like
      disease of horses, and in controls. Six horses with heaves and five aged-matched
      controls kept in the same environment were studied. Nuclear protein expression of
      SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial
      biopsies obtained during disease remission and after 1 and 30 days of naturally
      occurring antigenic exposure using immunohistochemistry and immunofluorescence
      techniques. Nuclear expression of SRF (P = 0.03, remission vs. 30 days) and MYOCD
      (P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of
      horses with heaves during disease exacerbation, while MYOCD (P = 0.04, remission
      vs. 30 days) decreased in the central airways of control horses. No changes were
      observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF
      and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM
      observed in equine asthmatic airways, while the remodeling of the central airways
      is more static or involves different transcription factors. 

PMID- 25979078
TI  - Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary
      disease: a longitudinal study.
AB  - A previous study involving a proteomic screen of induced sputum from smokers and
      patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated
      levels of bactericidal/permeability-increasing fold-containing protein B1
      (BPIFB1). The aim of the present study was to further evaluate the association of
      sputum BPIFB1 levels with smoking and longitudinal changes in lung function in
      smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel
      electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was
      investigated by immunoblotting and immunohistochemistry using sputum and lung
      tissue samples. BPIFB1 levels were also assessed in induced sputum from
      nonsmokers (n = 31), smokers (n = 169), and patients with COPD (n = 52) via an
      ELISA-based method. The longitudinal changes in lung function during the 4-year
      follow-up period were compared with the baseline sputum BPIFB1 levels. In lung
      tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia.
      Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of
      patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1
      levels correlated with pack-years and lung function as measured by forced
      expiratory volume in 1 s (FEV1) % predicted and FEV1/FVC (forced vital capacity)
      at baseline and after the 4-year follow-up in all participants. The changes in
      lung function over 4 years were significantly associated with BPIFB1 levels in
      current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1
      were associated with changes of lung function over time, especially in current
      smokers with COPD. BPIFB1 may be involved in the pathogenesis of smoking-related
      lung diseases. 

PMID- 25979079
TI  - Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor
      exposures.
AB  - The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung
      health. Having previously shown that cigarette smoke (CS) extract disrupts the
      lung microvasculature barrier function by endothelial cell activation and
      cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or
      e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular
      endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig
      vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions.
      Compared with nicotine-containing extract, nicotine free-CS extract (10-20%)
      caused significantly less endothelial permeability as measured with electric cell
      substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of
      endothelial barrier in cultured cell monolayers and rapidly increased lung
      inflammation and oxidative stress in mice. The endothelial barrier disruptive
      effects were associated with increased intracellular ceramides, p38 MAPK
      activation, and myosin light chain (MLC) phosphorylation, and was critically
      mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1.
      Although nicotine at sufficient concentrations to cause endothelial barrier loss
      did not trigger cell necrosis, it markedly inhibited cell proliferation.
      Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both
      endothelial cell proliferation and barrier function during nicotine exposures.
      Nicotine-independent effects of e-Cig solutions were noted, which may be
      attributable to acrolein, detected along with propylene glycol, glycerol, and
      nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig
      solutions and vapor. These results suggest that soluble components of e-Cig,
      including nicotine, cause dose-dependent loss of lung endothelial barrier
      function, which is associated with oxidative stress and brisk inflammation. 

PMID- 25979080
TI  - Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease.
AB  - During the last decade, there have been major advances in knowledge of the
      effects of oxygen therapy in patients with acute exacerbations of chronic
      obstructive pulmonary disease. This includes a randomised controlled trial of
      oxygen therapy in the pre-hospital setting, which showed that high concentration
      oxygen therapy leads to a 2.4-fold increased risk of mortality compared with
      titrated oxygen therapy to maintain oxygen saturations (SpO2) within a target
      range of 88-92%. Professional guidelines now recommend the use of supplementary
      oxygen in acute exacerbations of chronic obstructive pulmonary disease only if
      the SpO2 is less than 88%, with titration to achieve an SpO2 of 88-92%, and the
      delivery of bronchodilators by air-driven nebulisation or metered dose inhaler
      with a spacer. The aim of this review is to provide an overview of the evidence
      base that underpins these recommendations. We suggest that their implementation
      will require important changes to current clinical practice in which there is an
      entrenched culture of the use of high concentration oxygen therapy. 

PMID- 25979081
TI  - Staying Positive: Positive Affect as a Predictor of Resilience in Adolescents
      With Type 1 Diabetes.
AB  - BACKGROUND: Adolescents with Type 1 Diabetes (T1D) are at increased risk for
      diminished quality of life, deteriorating glycemic control, and psychological
      symptoms, yet some adolescents are able to adapt to the challenges associated
      with having diabetes exceptionally well. We sought to examine positive affect as
      a protective process predicting resilience over time in youth with T1D. METHOD:
      Adolescents and their mothers completed questionnaire data, and HbA1c was
      obtained from adolescents' medical records at baseline and after 6 months.
      Adolescents were coded for observed positive mood during a videotaped interaction
      with their mothers. RESULTS: Positive mood, including both self-report and
      observed mood, was associated with glycemic control, psychological symptoms, and
      quality of life. In addition, positive mood predicted improvements in glycemic
      control and externalizing problems over 6 months. CONCLUSIONS: Positive affect
      emerged as a protective process for resilient outcomes in adolescents with T1D,
      suggesting novel targets for intervention in this high-risk population.

PMID- 25979082
TI  - Child Abuse, Resting Blood Pressure, and Blood Pressure Reactivity to
      Psychosocial Stress.
AB  - OBJECTIVE: Childhood trauma is associated with hypertension in adults. It is
      unknown whether childhood trauma predicts elevated blood pressure earlier in
      development. We investigated whether the trauma of child abuse was associated
      with blood pressure in adolescents. METHODS: The sample included 145 adolescents
      aged 13-17 years, 40% with exposure to child abuse. The mean age of participants
      was 14.93 years (SD = 1.33); 58% were female. The majority self-identified as non
      Hispanic White (43%), with the remainder identifying as non-Hispanic Black (17%),
      Hispanic (17%), or other/mixed race (23%). We used established age/sex/height
      specific cutoffs to determine the prevalence of prehypertension and hypertension
      in the sample. We used two-sample t tests to examine associations of abuse with
      resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) and
      blood pressure reactivity to the Trier Social Stress Test and a frustration task.
      We used linear regression to adjust for potential confounders including
      sociodemographic variables, body mass index, smoking, and psychopathology.
      RESULTS: Mean resting SBP and DBP were 114.07 mmHg and 61.35 mmHg in those with a
      history of abuse and 111.39 mmHg and 56.89 mmHg in those without a history of
      abuse. This difference was significant for DBP only. Twelve percent of
      participants met criteria for prehypertension or hypertension based on resting
      blood pressure values; this did not differ between those with and without an
      abuse history. Child abuse was associated with lower DBP and SBP reactivity to
      laboratory stress tasks and reduced DBP reactivity to frustration. These
      associations were robust to adjustment for potential confounders. CONCLUSIONS:
      Child abuse is associated with higher resting DBP and blunted DBP and SBP
      reactivity to laboratory stress in adolescence. These findings suggest a
      potential pathway by which child abuse leads to hypertension.

PMID- 25979083
TI  - Protective Factors in Young Children With Type 1 Diabetes.
AB  - OBJECTIVE: To characterize protective factors in young children with type 1
      diabetes, and evaluate associations among child protective factors and indicators
      of diabetes resilience, including better child and parent psychosocial
      functioning and glycemic control. METHODS: Parents of 78 young children with type
      1 diabetes reported on child protective factors, child quality of life, parent
      depressive symptoms, and disease-specific parenting stress. A1c values were
      collected from medical records. RESULTS: Young children with type 1 diabetes were
      rated as having similar levels of protective factors as normative samples.
      Greater child protective factors were associated with indicators of diabetes
      resilience, including higher child quality of life and lower parent depressive
      symptoms and parenting stress. Regression analyses demonstrated that child
      protective factors were associated with 16% of the variance in parent-reported
      depressive symptoms. CONCLUSIONS: Attention to child protective factors can
      enhance understanding of adjustment to type 1 diabetes and may have implications
      for intervention.

PMID- 25979084
TI  - Parent-Child Relationship Quality and Gender as Moderators of the Influence of
      Hurricane Exposure on Physical Health Among Children and Youth.
AB  - OBJECTIVE: To investigate the long-term influence of disaster exposure, parent
      child relationship quality (PCRQ), and gender on child and youth physical health.
      METHODS: Parent-child dyads (N = 1,886) were randomly selected and interviewed
      approximately 18 months after Hurricane Georges hit Puerto Rico (1998), and
      reinterviewed 12 months later. The outcome variables were parent report of a
      global rating of children's physical health, and frequency of medical problems
      and medical visits in the past year. RESULTS: Conservative analyses that
      accounted for a host of postdisaster health-relevant factors showed that
      hurricane exposure exerted detrimental influence on physical health at both 18
      and 30 months after the event. The moderating role of PCRQ in the relation
      between hurricane exposure and physical health varied by gender. CONCLUSION:
      Disasters have long-term potential to influence the physical health of children
      and adolescents. PCRQ serves as resource but its role in the context of disasters
      is complex.

PMID- 25979085
TI  - Topical Review: Resilience Resources and Mechanisms in Pediatric Chronic Pain.
AB  - OBJECTIVE: To apply resilience theory and the extant literature to propose a
      resilience-risk model for pediatric chronic pain and provide an agenda for
      research and clinical practice in pediatric chronic pain resilience.  METHOD:
      Literature review to develop a resilience-risk model for pediatric chronic pain.
      RESULTS: The chronic pain literature has identified unique individual and
      social/environmental resilience resources and pain-related resilience mechanisms
      that promote pain adaptation. These data support our ecological resilience-risk
      model for pediatric chronic pain, and the model highlights novel directions for
      clinical and research efforts for youth with chronic pain. CONCLUSIONS: The
      examination of pediatric chronic pain from a strengths-based approach might lead
      to novel clinical avenues to empower youth to positively adapt and live beyond
      their pain.

PMID- 25979086
TI  - Evidence for Mediodorsal Thalamus and Prefrontal Cortex Interactions during
      Cognition in Macaques.
AB  - It is proposed that mediodorsal thalamus contributes to cognition via
      interactions with prefrontal cortex. However, there is relatively little evidence
      detailing the interactions between mediodorsal thalamus and prefrontal cortex
      linked to cognition in primates. This study investigated these interactions
      during learning, memory, and decision-making tasks in rhesus monkeys using a
      disconnection lesion approach. Preoperatively, monkeys learned object-in-place
      scene discriminations embedded within colorful visual backgrounds. Unilateral
      neurotoxic lesions to magnocellular mediodorsal thalamus (MDmc) impaired the
      ability to learn new object-in-place scene discriminations. In contrast,
      unilateral ablations to ventrolateral and orbital prefrontal cortex (PFv+o) left
      learning intact. A second unilateral MDmc or PFv+o lesion in the contralateral
      hemisphere to the first operation, causing functional MDmc-PFv+o disconnection
      across hemispheres, further impaired learning object-in-place scene
      discriminations, although object discrimination learning remained intact.
      Adaptive decision-making after reward satiety devaluation was also reduced. These
      data highlight the functional importance of interactions between MDmc and PFv+o
      during learning object-in-place scene discriminations and adaptive decision
      making but not object discrimination learning. Moreover, learning deficits
      observed after unilateral removal of MDmc but not PFv+o provide direct behavioral
      evidence of the MDmc role influencing more widespread regions of the frontal
      lobes in cognition. 

PMID- 25979088
TI  - Defects During Mecp2 Null Embryonic Cortex Development Precede the Onset of Overt
      Neurological Symptoms.
AB  - MeCP2 is associated with several neurological disorders; of which, Rett syndrome
      undoubtedly represents the most frequent. Its molecular roles, however, are still
      unclear, and data from animal models often describe adult, symptomatic stages,
      while MeCP2 functions during embryonic development remain elusive. We describe
      the pattern and timing of Mecp2 expression in the embryonic neocortex
      highlighting its low but consistent expression in virtually all cells and show
      the unexpected occurrence of transcriptional defects in the Mecp2 null samples at
      a stage largely preceding the onset of overt symptoms. Through the deregulated
      expression of ionic channels and glutamatergic receptors, the lack of Mecp2
      during early neuronal maturation leads to the reduction in the neuronal
      responsiveness to stimuli. We suggest that such features concur to morphological
      alterations that begin affecting Mecp2 null neurons around the perinatal age and
      become evident later in adulthood. We indicate MeCP2 as a key modulator of the
      transcriptional mechanisms regulating cerebral cortex development. Neurological
      phenotypes of MECP2 patients could thus be the cumulative result of different
      adverse events that are already present at stages when no obvious signs of the
      pathology are evident and are worsened by later impairments affecting the central
      nervous system during maturation and maintenance of its functionality.

PMID- 25979087
TI  - Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals
      onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent
      Female Mice Is Associated with Suppression of Food Restriction-Evoked
      Hyperactivity and Resilience to Activity-Based Anorexia.
AB  - Many, but not all, adolescent female mice that are exposed to a running wheel
      while food restricted (FR) become excessive wheel runners, choosing to run even
      during the hours of food availability, to the point of death. This phenomenon is
      called activity-based anorexia (ABA). We used electron microscopic
      immunocytochemistry to ask whether individual differences in ABA resilience may
      correlate with the lengths of axo-somatic contacts made by GABAergic axon
      terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact
      lengths were, on average, 40% greater for the ABA-induced mice, relative to
      controls. Correspondingly, the proportion of L5P perikaryal plasma membrane
      contacted by GABAergic terminals was 45% greater for the ABA mice. Contact
      lengths in the anterior cingulate cortex correlated negatively and strongly with
      the overall wheel activity after FR (R = -0.87, P < 0.01), whereas those in the
      prelimbic cortex correlated negatively with wheel running specifically during the
      hours of food availability of the FR days (R = -0.84, P < 0.05). These negative
      correlations support the idea that increases in the glutamic acid decarboxylase
      (GAD) terminal contact lengths onto L5P contribute toward ABA resilience through
      suppression of wheel running, a behavior that is intrinsically rewarding and
      helpful for foraging but maladaptive within a cage.

PMID- 25979089
TI  - Task-Specific Facilitation of Cognition by Anodal Transcranial Direct Current
      Stimulation of the Prefrontal Cortex.
AB  - We previously speculated that depression of cerebellar excitability using
      cathodal transcranial direct current stimulation (tDCS) might release extra
      cognitive resources via the disinhibition of activity in prefrontal cortex. The
      objective of the present study was to investigate whether anodal tDCS over the
      prefrontal cortex could similarly improve performance when cognitive demands are
      high. Sixty-three right-handed participants in 3 separate groups performed the
      Paced Auditory Serial Addition Task (PASAT) and the more difficult Paced Auditory
      Serial Subtraction Task (PASST), before and after 20 min of anodal, cathodal, or
      sham stimulation over the left dorsolateral prefrontal cortex (DLPFC).
      Performance was assessed in terms of the accuracy, latency, and variability of
      correct verbal responses. All behavioral measures significantly improved for the
      PASST after anodal DLPFC stimulation, but not the PASAT. There were smaller
      practice effects after cathodal and sham stimulation. Subjective ratings of
      attention and mental fatigue were unchanged by tDCS over time. We conclude that
      anodal stimulation over the left DLPFC can selectively improve performance on a
      difficult cognitive task involving arithmetic processing, verbal working memory,
      and attention. This result might be achieved by focally improving executive
      functions and/or cognitive capacity when tasks are difficult, rather than by
      improving levels of arousal/alertness. 

PMID- 25979092
TI  - The acetyl-CoA carboxylase enzyme: a target for cancer therapy?
AB  - As a rate-limiting enzyme, the acetyl-CoA carboxylase (ACC) is essential for
      fatty acid synthesis. Traditionally, the ACC has been a target of metabolic
      syndrome and obesity. Recent research has demonstrated that malignant tumors have
      a high energy flow, thus having a great ability to synthesize fatty acids. ACCs
      are occasionally found to be overexpressed in cancer cells, and using chemical or
      RNA interference to inhibit ACC can lead to cancer cell cycle arrest and
      apoptosis. This suggests that ACC and relative fatty acids may be critical for
      the survival of cancer cells. In this review, we summarize the role of ACC in
      tumor development. We also discuss the signaling pathways possibly affected by
      ACC, which may give insight into future research for cancer therapy. 

PMID- 25979090
TI  - Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar
      and Cell-Type Specificity.
AB  - Despite many previous studies, the functional innervation pattern of thalamic
      axons and their target specificity remains to be investigated thoroughly. Here,
      in primary auditory cortical slices, we examined thalamic innervation patterns
      for excitatory and different types of inhibitory neurons across laminae, by
      optogenetically stimulating axons from the medial geniculate body. We found that
      excitatory cells and parvalbumin (PV)-expressing inhibitory neurons across layer
      2/3 (L2/3) to L6 are directly innervated by thalamic projections, with the
      strongest innervation occurring in L4. The innervation of PV neurons is stronger
      than that of excitatory neurons in the same layer, with a relatively constant
      ratio between their innervation strengths across layers. For somatostatin and
      vasoactive intestinal peptide inhibitory neurons, essentially only L4 neurons
      were innervated by thalamic axons and the innervation was much weaker compared
      with excitatory and PV cells. In addition, more than half of inhibitory neurons
      in L1 were innervated, relatively strongly, by thalamic axons. Similar
      innervation patterns were also observed in the primary visual cortex. Thus,
      thalamic information can be processed independently and differentially by
      different cortical layers, in addition to the generally thought hierarchical
      processing starting from L4. This parallel processing is likely shaped by
      feedforward inhibition from PV neurons in each individual lamina, and may extend
      the computation power of sensory cortices.

PMID- 25979093
TI  - Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of
      Narcolepsy.
AB  - OBJECTIVES: To determine the diagnostic values, longitudinal stability, and HLA
      association of the sleep stage transitions in narcolepsy. METHODS: To compare the
      baseline differences in the sleep stage transition to REM sleep among 35 patients
      with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected
      relatives, and 159 non-narcoleptic sleep patient controls, followed by a
      reassessment at a mean duration of 37.4 months. RESULTS: The highest prevalence
      of altered transition from stage non-N2/N3 to stage R in multiple sleep latency
      test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type
      1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy
      (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and
      1.3%). Individual sleep variables had varied sensitivity and specificity in
      diagnosing narcolepsy. By incorporating a combination of sleep variables, the
      decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced
      specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy,
      respectively. There was a significant association of DBQ1*0602 with the altered
      sleep stage transition (OR = 16.0, 95% CI: 1.7-149.8, p = 0.015). The persistence
      of the altered sleep stage transition in both MSLT and NPSG was high for both
      type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively.
      CONCLUSION: Altered sleep stage transition is a significant and stable marker of
      narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in
      narcolepsy. Altered sleep stage transition has a significant diagnostic value in
      the differential diagnosis of hypersomnias, especially when combined with other
      diagnostic sleep variables in decision tree analysis.

PMID- 25979094
TI  - Preoperative Sleep Disruption and Postoperative Delirium.
AB  - STUDY OBJECTIVES: To describe preoperative and postoperative sleep disruption and
      its relationship to postoperative delirium. DESIGN: Prospective cohort study with
      6 time points (3 nights pre-hospitalization and 3 nights post-surgery). SETTING:
      University medical center. PATIENTS: The sample consisted of 50 English-speaking
      patients >= 40 years of age scheduled for major non-cardiac surgery, with an
      anticipated hospital stay >= 3 days. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Sleep was measured before and after surgery for a total of 6 days using
      a wrist actigraph to quantify movement in a continuous fashion. Postoperative
      delirium was measured by a structured interview using the Confusion Assessment
      Method. Sleep variables for patients with (n = 7) and without (n = 43)
      postoperative delirium were compared using the unpaired Student t-tests or chi(2)
      tests. Repeated measures analysis of variance for the 6 days was used to examine
      within-subject changes over time and between group differences. The mean age of
      the patients was 66 +/- 11 years (range 43-91 years), and it was not associated
      with sleep variables or postoperative delirium. The incidence of postoperative
      delirium observed during any of the 3 postoperative days was 14%. For the 7
      patients who subsequently developed postoperative delirium, wake after sleep
      onset (WASO) as a percentage of total sleep time was significantly higher (44% +/
      22%) during the night before surgery compared to the patients who did not
      subsequently developed delirium (21% +/- 20%, p = 0.012). This sleep disruption
      continued postoperatively, and to a greater extent, for the first 2 nights after
      surgery. Patients with WASO < 10% did not experience postoperative delirium. Self
      reported sleep disturbance did not differ between patients with vs. without
      postoperative delirium. CONCLUSIONS: In this pilot study of adults over 40 years
      of age, sleep disruption was more severe before surgery in the patients who
      experienced postoperative delirium. A future larger study is necessary to confirm
      our results and determine if poor sleep is associated with delirium in larger
      samples and what specific sleep problems best predict postoperative delirium in
      older surgical patients.

PMID- 25979095
TI  - Adverse Effects of Daylight Saving Time on Adolescents' Sleep and Vigilance.
AB  - STUDY OBJECTIVES: Daylight saving time (DST) has been established with the intent
      to reduce energy expenditure, however unintentional effects on sleep and
      vigilance have not been consistently measured. The objective of this study was to
      test the hypothesis that DST adversely affects high school students' sleep and
      vigilance on the school days following its implementation. METHODS: A natural
      experiment design was used to assess baseline and post-DST differences in
      objective and subjective measures of sleep and vigilance by actigraphy, sleep
      diary, sleepiness scale, and psychomotor vigilance testing (PVT). Students were
      tested during school days immediately preceding and following DST. RESULTS: A
      total of 40 high school students were enrolled in this study; 35 completed the
      protocol. Sleep duration declined by an average of 32 minutes on the weeknights
      post-DST, reflecting a cumulative sleep loss of 2 h 42 min as compared to the
      baseline week (p = 0.001). This finding was confirmed by sleep diary analyses,
      reflecting an average sleep loss of 27 min/night (p = 0.004) post-DST. Vigilance
      significantly deteriorated, with a decline in PVT performance post-DST, resulting
      in longer reaction times (p < 0.001) and increased lapses (p < 0.001). Increased
      daytime sleepiness was also demonstrated (p < 0.001). CONCLUSION: The early March
      DST onset adversely affected sleep and vigilance in high school students
      resulting in increased daytime sleepiness. Larger scale evaluations of sleep
      impairments related to DST are needed to further quantify this problem in the
      population. If confirmed, measures to attenuate sleep loss post-DST should be
      implemented.

PMID- 25979096
TI  - Hypocretin Deficiency Associated with Narcolepsy Type 1 and Central
      Hypoventilation Syndrome in Neurosarcoidosis of the Hypothalamus.
AB  - We report a case of a 53-year-old man presenting with depressed alertness and
      severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging
      demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin
      level of 0 pg/mL. The patient also experienced respiratory depression that
      presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result
      of extensive diencephalic injury. This is a novel case, demonstrating both
      hypocretin deficiency syndrome, as well as respiratory dysfunction from
      destruction of hypocretin neurons and extensive destruction of key diencephalic
      structures secondary to the underlying neurosarcoidosis.

PMID- 25979097
TI  - Sleeping for Two: The Great Paradox of Sleep in Pregnancy.

PMID- 25979099
TI  - Sleep Education in Schools: Where Do We Stand?

PMID- 25979098
TI  - Bispectral Index in Evaluating Effects of Sedation Depth on Drug-Induced Sleep
      Endoscopy.
AB  - OBJECTIVE: To evaluate the effect of sedation depth on drug-induced sleep
      endoscopy (DISE). METHODS: Ninety patients with obstructive sleep apnea (OSA) and
      18 snorers underwent polysomnography and DISE under bispectral index (BIS)-guided
      propofol infusion at two different sedation levels: BIS 65-75 (light sedation)
      and 50-60 (deep sedation). RESULTS: For the patients with OSA, the percentages of
      velopharynx, oropharynx, hypopharynx, and larynx obstructions under light
      sedation were 77.8%, 63.3%, 30%, and 33.3%, respectively. Sedation depth was
      associated with the severity of velopharynx and oropharynx obstruction,
      oropharynx obstruction pattern, tongue base obstruction, epiglottis
      anteroposterior prolapse and folding, and arytenoid prolapse. In comparison, OSA
      severity was associated with the severity of velopharynx obstruction, severity of
      oropharynx obstruction, and arytenoid prolapse (odds ratio (95% confidence
      interval); 14.3 (4.7-43.4), 11.7 (4.2-32.9), and 13.2 (2.8-62.3), respectively).
      A good agreement was noted between similar DISE findings at different times and
      different observers (kappa value 0.6 to 1, respectively). A high percentage of
      arytenoid prolapse (46.7% among the patients with OSA under light sedation) was
      noted. CONCLUSIONS: Greater sedative depth increased upper airway collapsibility
      under DISE assessment. DISE under BIS-guided propofol infusion, and especially a
      level of 65-75, offers an objective and reproducible method to evaluate upper
      airway collapsibility. Some findings were induced by drug sedation and need
      careful interpretation. Specific arytenoid prolapse patterns were noted for which
      further investigations are warranted. CLINICAL TRIALS REGISTRATION:
      http://www.clinicaltrials.gov, identifier: NCT01100554. COMMENTARY: A commentary
      on this article appears in this issue on page 965.

PMID- 25979100
TI  - Feasibility and Efficacy of a Self-Management Intervention for Insomnia in Stable
      Heart Failure.
AB  - BACKGROUND: Chronic insomnia is common among patients with heart failure (HF) and
      may contribute to fatigue and poor function. However, to date there have been no
      randomized controlled trials focused on treatment of insomnia or daytime symptoms
      in this population. OBJECTIVES: The purpose of this study was to examine the
      preliminary efficacy, feasibility, and acceptability of a self-management
      intervention (cognitive behavioral therapy [CBT-I]) for insomnia among patients
      with stable HF. METHODS: We conducted a pilot randomized controlled trial (RCT)
      in which patients with stable Class I-III HF (n = 25/52.1% women; mean age = 59
      +/- 14.8 years) were randomized in groups to CBT-I (n = 29) or an attention
      control condition (HF self-management with sleep hygiene; n = 19). Participants
      completed 2 weeks of wrist actigraphy, the insomnia severity index, and measures
      of fatigue, depression, sleepiness, and functional performance at baseline and
      follow-up. We computed the size of the effects on the dependent variables and
      used MANOVA to evaluate the effects of CBT-I on insomnia and fatigue. RESULTS:
      CBT-I was feasible and acceptable and had a statistically significant effect on
      insomnia and fatigue, while controlling for the effects of comorbidity and age.
      CONCLUSIONS: CBT-I has short-term efficacy as a treatment for chronic insomnia
      among patients with stable HF. Future studies are needed to address its sustained
      effects.

PMID- 25979101
TI  - The Association between Short or Long Sleep Times and Quality of Life (QOL):
      Results of the Korea National Health and Nutrition Examination Survey (KNHANES IV
      V).
AB  - STUDY OBJECTIVES: Sleep can affect quality of life (QOL). We examined the
      association between self-reported sleep time and QOL independent of perceived
      health status and depressive disorder using the EuroQol-5 Dimension (EQ-5D) and a
      visual analog scale (VAS). METHODS: We used the nationwide cross-sectional survey
      data of 28,178 subjects from the Korea National Health and Nutrition Examination
      Survey (KNHANES) IV-V. Self-reported sleep time was assessed by average hours of
      sleep per day. QOL was measured using the EQ-5D and VAS. A generalized additive
      model and multiple linear regression analysis were used to estimate the effect of
      sleep time on the QOL while adjusting for potential confounding variables.
      RESULTS: We found a significant inverted U-shaped relationship between sleep time
      and QOL using both the EQ-5D and VAS indices. Compared with subjects who slept 7
      h/day, Korean men whose sleep time was very short (<= 4 h/ day) or very long (>=
      10 h/day) had substantially worse QOL (-3.125 in EQ-5D, p < 0.001 and -4.387 on
      the VAS, p = 0.000 for <= 4 h/day; -1.763 in EQ-5D, p = 0.001 and -1.944 on the
      VAS for >= 10 h/day, all p = 0.038). A similar inverted U-shape was observed
      between sleep time and QOL in Korean women. CONCLUSIONS: Inappropriate sleep time
      (either short or long) in both men and women was significantly associated with
      lower QOL. In particular, such an association was more apparent among persons
      whose perceived health status was poor.

PMID- 25979102
TI  - Anatomically Based Outcome Predictors of Treatment for Obstructive Sleep Apnea
      with Intraoral Splint Devices: A Systematic Review of Cephalometric Studies.
AB  - AIMS: The aim of this review is to summarize data from the literature on the
      predictive value of anatomy-based parameters, as identified by cephalometry, for
      the efficacy of mandibular advancement devices (MAD) for the treatment of
      obstructive sleep apnea (OSA). METHODS: Articles were initially selected based on
      their titles or abstracts. Full articles were then retrieved and further
      scrutinized according to predetermined criteria. Reference lists of selected
      articles were searched for any missed publications. The selected articles were
      methodologically evaluated. RESULTS: Of an initial 311 references, 13 were
      selected that assessed correlations between polysomnographic and cephalometric
      variables. The majority of studies demonstrated a correlation between treatment
      effectiveness and features as determined by cephalometric analysis, such as the
      mandibular plane angle, hyoid bone distance to mandible, antero-posterior
      diameter of the maxilla, tongue area, cranial base, and soft palate. CONCLUSIONS:
      The mandibular plane angle and the distance between hyoid bone and mandibular
      plane was found to have a predictive value for MAD effectiveness in OSA patients.
      However, the relative weak and somewhat inconsistent cephalometric data suggest
      that decisions based solely on these factors cannot be recommended, especially
      because an integrated analysis of other risk factors (e.g., age, sex, BMI) should
      also be taken into account.

PMID- 25979103
TI  - Effect of Wakefulness-Promoting Agents on Sleepiness in Patients with Sleep Apnea
      Treated with CPAP: A Meta-Analysis.
AB  - STUDY OBJECTIVES: To perform a meta-analysis of the effect of wakefulness
      promoting agents (modafinil and armodafinil) in patients with residual sleepiness
      after CPAP therapy for obstructive sleep apnea. METHODS: We conducted a
      systematic search of MEDLINE (1966 to September 2014), EMBASE (1980 to September
      2014) and Cochrane Database for randomized placebo controlled trials on modafinil
      or armodafinil in patients who met established criteria for diagnosis of
      obstructive sleep apnea, adequate continuous positive airway pressure use, and
      who complained of residual sleepiness. Risk of bias was assessed. Primary
      outcomes were the Epworth Sleepiness Scale and mean sleep latencies on the
      maintenance of wakefulness test. Secondary outcomes were the Clinical Global
      Impression of Change, change in daily continuous positive airway pressure use,
      and the frequency of headaches. RESULTS: Out of 118 abstracts screened and 12
      full text articles reviewed, we included 6 studies (total of 1,479 participants)
      in our final meta-analysis: Three evaluated modafinil, and three armodafinil.
      Risk of bias was unclear in one or more key domains for four studies. When
      compared with placebo, wakefulness promoting agents decreased Epworth Sleepiness
      Scale by 2.51 points (95% CI, 2.00-3.02), increased sleep latency in maintenance
      of wakefulness test by 2.73 minutes (95% CI, 2.12-3.34), increased the reporting
      of minimal improvement on the Clinical Global Impression of Change by 26% (RR
      1.59; 95% CI, 1.36-1.86), and increased the risk of headaches by 8% (RR 1.98; 95%
      CI, 1.48-2.63). Also, there was a trend for decreased continuous positive airway
      pressure after treatment with these agents. CONCLUSION: Wakefulness promoting
      agents improve objective and subjective measures of sleepiness, wakefulness,
      perception of disease severity in patients with residual sleepiness after CPAP
      therapy for OSA, and are generally well tolerated.

PMID- 25979104
TI  - Effect of CPAP on Cardiac Function in Minimally Symptomatic Patients with OSA:
      Results from a Subset of the MOSAIC Randomized Trial.
AB  - STUDY OBJECTIVES: Minimally symptomatic obstructive sleep apnea (OSA) is highly
      prevalent, and the effects of continuous positive airway pressure (CPAP) on
      myocardial function in these patients are unknown. The MOSAIC randomized,
      controlled trial of CPAP for minimally symptomatic OSA assessed the effect of
      CPAP on myocardial function in a subset of patients. METHODS: Two centers taking
      part in the MOSAIC trial randomized 238 patients in parallel to 6 months of CPAP
      (120) or standard care (118). Of these, 168 patients had echocardiograms, and 68
      patients had a cardiac magnetic resonance scan (CMR). A larger group (314) from 4
      centers had brain natriuretic peptide (BNP) measured. RESULTS: Mean (SD) baseline
      oxygen desaturation index (ODI) and Epworth sleepiness score (ESS) were 13.5
      (13.2), and 8.4 (4.0), respectively. CPAP significantly reduced ESS and ODI.
      Baseline LV ejection fraction (LVEF) was well preserved (60.4%). CPAP had no
      significant effect on echo-derived left atrial (LA) area (-1.0 cm2, 95% CI -2.6
      to +0.6, p = 0.23) or early to late left ventricular filling velocity (E/A) ratio
      (-0.01, 95% CI -0.07 to +0.05, p = 0.79). There was a small change in echo
      derived LV end diastolic volume (EDV) with CPAP (-5.9 mL, 95% CI -10.6 to -1.2, p
      = 0.015). No significant changes were detected by CMR on LV mass index (+1.1
      g/m(2), 95% CI -5.9 to +8.0, p = 0.76) or LVEF (+0.8%, 95% CI -1.2 to +2.8, p =
      0.41). CPAP did not affect BNP levels (p = 0.16). CONCLUSIONS: Six months of CPAP
      therapy does not change cardiac functional or structural parameters measured by
      echocardiogram or CMR in patients with minimally symptomatic mild-to-moderate
      OSA. CLINICAL TRIAL REGISTRATION: ISRCTN 34164388 (http://isrctn.org).

PMID- 25979105
TI  - Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of
      the American Academy of Sleep Medicine and Sleep Research Society.
AB  - Sleep is essential for optimal health. The American Academy of Sleep Medicine
      (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for
      the amount of sleep needed to promote optimal health in adults, using a modified
      RAND Appropriateness Method process. The recommendation is summarized here. A
      manuscript detailing the conference proceedings and evidence supporting the final
      recommendation statement will be published in SLEEP and the Journal of Clinical
      Sleep Medicine.

PMID- 25979106
TI  - Proximal muscle weakness in severe lead poisoning from retained bullet fragments.

PMID- 25979107
TI  - Raising awareness for a low health-related quality of life in intoxicated ICU
      patients.

PMID- 25979108
TI  - Diagnostic accuracy of endostatin for malignant pleural effusion: A clinical
      study and meta-analysis.
AB  - BACKGROUND: The diagnosis of malignant pleural effusion (MPE) remains a clinical
      challenge. Many studies suggest that endostatin is a potential marker for MPE.
      This study aimed to determine the diagnostic value of endostatin with respect to
      MPE and to summarize the overall diagnostic performance of endostatin via a meta
      analysis. METHODS: Pleural effusion samples from patients with both malignant and
      nonmalignant disease were collected, and the pleural levels of endostatin and
      carcino-embryonic antigen (CEA) were subsequently measured. The diagnostic
      performances of endostatin and CEA were analyzed via standard receiver operator
      characteristic curve analysis methods, using the AUC as a measure of accuracy.
      The overall diagnostic accuracy of endostatin for MPE was summarized through a
      bivariate meta-analysis with standard method recommended. RESULTS: Fifty-two
      patients with MPEs and 64 patients with benign pleural effusions (BPEs) were
      included this study. Pleural endostatin levels were significantly increased in
      the setting of MPE compared with BPE (104.78 +/- 64.58 vs. 56.81 +/- 28.84 ng/ml;
      p < 0.001). Using a cutoff value of 79.7 ng/ml, the sensitivity and specificity
      of endostatin in diagnosing MPE were shown to be 51.92% and 85.94%, respectively,
      and the AUC was 0.747. The combination of endostatin and CEA enhanced diagnostic
      performance with respect to MPE. In addition to this study, another eight studies
      were included in this meta-analysis. The pooled diagnostic estimates were 0.69
      for sensitivity and 0.78 for specificity. The positive likelihood ratio and
      negative likelihood ratio for endostatin were 3.16 and 0.40, respectively. The
      diagnostic odds ratio was 7.89, and the AUC of the summary receiver operator
      characteristic curve was 0.79. CONCLUSION: Pleural levels of endostatin are
      increased in the setting of MPE. However, endostatin exhibits a limited efficacy
      for the diagnosis of MPE and shows a relatively low sensitivity. The assessment
      of endostatin in combination with CEA may enhance diagnostic accuracy with
      respect to MPE.

PMID- 25979110
TI  - The discovery and development of omalizumab for the treatment of asthma.
AB  - INTRODUCTION: The evolution in immunological methods used to assess human
      allergic diseases has led to the identification of immunoglobulin E (IgE) as a
      diagnostic biomarker and a potential therapeutic target. Innovative technologies
      in molecular biology and immunogenetics contributed to the development of a
      selective blocking agent, disclosing new therapeutic perspectives in the
      treatment of allergic asthma. Omalizumab is the most advanced humanized anti-IgE
      monoclonal antibody that specifically binds serum-free IgE. Omalizumab also
      interrupts the allergic cascade by preventing binding of IgE with FcepsilonRI
      receptors on mast cells, basophils, antigen-presenting cells and other
      inflammatory cells. AREAS COVERED: This review discusses the discovery strategy
      and preclinical development of omalizumab. Furthermore, it also provides a
      clinical overview of the key trials leading to its launch and a detailed analysis
      of safety and post-marketing data. EXPERT OPINION: The clinical efficacy of
      omalizumab in allergic asthma has been well documented in clinical trials,
      involving adults, adolescents and children with moderate-to-severe and severe
      allergic asthma. To date, omalizumab has also been approved in chronic idiopathic
      urticaria for patients 12 years and older who remain symptomatic despite high
      dosages of H1 antihistamines. Omalizumab has also been investigated in many other
      different patient populations beyond allergic asthma and may yet have an
      application to other indications. While omalizumab is the only mAb available for
      treating allergic asthma, the authors anticipate that new mAbs will emerge in the
      future that overcome omalizumab's current limitations.

PMID- 25979109
TI  - The guanylate cyclase-C signaling pathway is down-regulated in inflammatory bowel
      disease.
AB  - OBJECTIVE: Activation of membrane receptor guanylate cyclase-C (GC-C) is
      implicated in gastrointestinal fluid and electrolyte balance, preservation of
      intestinal barrier integrity, anti-trophic effects and inhibition of pain
      sensation. To evaluate GC-C signaling, we examined the regulation of GC-C
      (GUCY2C/Gucy2c) and its endogenous ligands guanylin (GN/GUCA2A/Guca2a) and
      uroguanylin (UGN/GUCA2B/Guca2b) in colonic Crohn's disease (CD), ulcerative
      colitis (UC) and in rats with 2,4,6-Trinitrobenzene sulphonic acid (TNBS)
      colitis. Correlation analyses between expression of GUCA2A and GUCY2C and
      expression of inflammatory cytokines (IL1A, IL1B, TNFA and IFNG) were conducted.
      Additionally, expression of transcription factors for GUCA2A and GUCY2C, and the
      GC-C signaling pathway, were examined. MATERIAL AND METHODS: Biopsies from active
      UC/CD, un-inflamed UC/CD and healthy controls, and inflamed and healthy rat colon
      were investigated with gene expression microarray, immunohistochemistry (IHC) and
      in situ hybridization (ISH). RESULTS: GUCA2A/Guca2a, GUCA2B, GUCY2C/Gucy2c,
      transcription factors, as well as several cyclic guanosine-3',5'-monophosphate
      downstream mediators were all significantly down-regulated in both inflamed
      colonic inflammatory bowel disease (IBD) mucosa and TNBS colitis. Expression of
      GUCA2A and GUCY2C negatively correlated to expression of inflammatory cytokines.
      IHC and ISH confirmed microarray results for GUCA2A/Guca2a and GUCY2C/Gucy2c in
      inflamed samples. We identified a highly significant positive correlation between
      the expression of the transcription factor caudal type homeobox 2 (CDX2) and the
      expression of the downstream target gene GUCY2C. CONCLUSIONS: GUCA2A, GUCA2B and
      GUCY2C as well as several steps of the GC-C signaling pathway are down-regulated
      in IBD. This may have implications in IBD pathogenesis.

PMID- 25979111
TI  - Outcome of surgery for temporal lobe epilepsy in adults - A cohort study.
AB  - INTRODUCTION: The aim of the current study was to evaluate the factors associated
      with post-operative outcome in patients with temporal lobe epilepsy (TLE)
      undergoing Surgery. METHODS: We analyzed data of 288 consecutive patients
      operated for drug-resistant TLE. All the patients had at least one year post
      surgery follow-up. Logistic regression model was used to evaluate the predictive
      value of different factors for outcome. RESULTS: The mean age at onset of
      epilepsy of the study population was 15.51 +/- 9.79 years; whereas the mean age
      at surgery was 32.16 +/- 9.45 years, with 125 (43.4%) women. The age at surgery
      was significantly lower in the patients with favourable outcome (30.26 +/- 9.05
      vs. 34.06 +/- 9.85 years; p = 0.007). The mean duration of epilepsy with age of
      onset below 12 years was higher than the rest (19.84 +/- 7.30 vs. 13.00 +/- 8.45
      years; p < 0.001). The histopathology showed hippocampal sclerosis in 203 (70.4%)
      of the patients; isolated focal cortical dysplasia was associated with
      unfavourable outcome (9.3% vs.2.6%; p = 0.036). The duration of follow up ranged
      from 1 to 10.3 years. Three patients died late in the follow up. At the last
      follow 73% were seizure free and Engel's favourable outcome was noted in 82%.
      Duration of epilepsy greater than ten years (beta = 6.997; 95%CI; 2.254-21.715; p
      = 0.01), younger age of onset of epilepsy (beta = 1.07; 95%CI; 1.014-1.132; p =
      0.015) and acute post operative seizures (APOS) (beta = 4.761; 95%CI; 1.946
      11.649; p = 0.001) were the predictors of unfavourable outcome. CONCLUSION:
      Following surgery for TLE, 73% were seizure free and Engel's favourable outcome
      was noted in 82%. The predictors of unfavourable outcome were younger age of
      onset, pronged duration and of epilepsy and APOS.

PMID- 25979112
TI  - Incidence of inflammatory bowel disease in Iceland 1995 - 2009. A nationwide
      population-based study.
AB  - OBJECTIVE: We analyzed the incidence of inflammatory bowel disease (IBD) in
      Iceland for the period 1995-2009. MATERIAL AND METHODS: New cases of ulcerative
      colitis (UC) and Crohn's disease (CD) were retrieved by thorough review of all
      small and large intestinal pathology reports with any type of inflammation from
      all the pathology departments in Iceland for the period 1995-2009. All suspicious
      new cases of IBD were then scrutinized retrospectively by examination of their
      clinical records. RESULTS: A total of 1175 cases of IBD were diagnosed, 884 UC,
      279 CD and 12 IBD unclassified. The crude annual incidence of UC was
      20.5/100,000, increasing from 18.1 the first 5-year period to 22.1 the last 5
      year period. The crude annual incidence of CD was 6.5/100,000, 6.7 the first 5
      year period and 6.6 the last 5-year period. CONCLUSIONS: This study shows
      statistically significant increase in the incidence of UC during the study
      period. The incidence of CD has however remained stable.

PMID- 25979114
TI  - Serine phosphorylation and arginine methylation at the crossroads to
      neurodegeneration.
AB  - Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease,
      polyglutamine diseases and motor neuron diseases, are late-onset and progressive
      disorders characterized by the accumulation of misfolded proteins inside and
      outside neurons. No effective therapies exist to delay the onset or arrest the
      progression of these diseases. One novel and promising therapeutic approach
      consists of targeting disease-causing proteins at the post-translational level.
      Here we illustrate this concept using the example of spinal and bulbar muscular
      atrophy, a neurodegenerative disease caused by polyglutamine expansion in the
      androgen receptor. Emerging evidence suggests that two key post-translational
      modifications of polyglutamine-expanded androgen receptor, namely serine
      phosphorylation by protein kinase B/Akt and arginine methylation by protein
      arginine methyltransferases, occur at the same consensus site, are mutually
      exclusive, and have opposing effects on neurotoxicity. Because several proteins
      linked to neurodegenerative diseases have canonical Akt consensus site motifs,
      these findings may have a broad impact in the field of neurological diseases
      caused by misfolded proteins. 

PMID- 25979113
TI  - Access to and value of information to support good practice for staff in Kenyan
      hospitals.
AB  - BACKGROUND: Studies have sought to define information needs of health workers
      within very specific settings or projects. Lacking in the literature is how
      hospitals in low-income settings are able to meet the information needs of their
      staff and the use of information communication technologies (ICT) in day-to-day
      information searching. OBJECTIVE: The study aimed to explore where professionals
      in Kenyan hospitals turn to for work-related information in their day-to-day
      work. Additionally, it examined what existing solutions are provided by hospitals
      with regard to provision of best practice care. Lastly, the study explored the
      use of ICT in information searching. DESIGN: Data for this study were collected
      in July 2012. Self-administered questionnaires (SAQs) were distributed across 22
      study hospitals with an aim to get a response from 34 health workers per
      hospital. RESULTS: SAQs were collected from 657 health workers. The most popular
      sources of information to guide work were fellow health workers and printed
      guidelines while the least popular were scientific journals. Of value to health
      workers were: national treatment policies, new research findings, regular reports
      from surveillance data, information on costs of services and information on their
      performance of routine clinical tasks; however, hospitals only partially met
      these needs. Barriers to accessing information sources included: 'not
      available/difficult to get' and 'difficult to understand'. ICT use for
      information seeking was reported and with demographic specific differences noted
      from the multivariate logistic regression model; nurses compared to medical
      doctors and older workers were less likely to use ICT for health information
      searching. Barriers to accessing Internet were identified as: high costs and the
      lack of the service at home or at work. CONCLUSIONS: Hospitals need to provide
      appropriate information by improving information dissemination efforts and
      providing an enabling environment that allows health workers find the information
      they need for best practice.

PMID- 25979115
TI  - Acute theophylline exposure modulates breathing activity through a cervical
      contusion.
AB  - Cervical spinal contusion injuries are the most common form of spinal cord injury
      (>50%) observed in humans. These injuries can result in the impaired ability to
      breathe. In this study we examine the role of theophylline in the rescue of
      breathing behavior after a cervical spinal contusion. Previous research in the C2
      hemisection model has shown that acute administration of theophylline can rescue
      phrenic nerve activity and diaphragmatic EMG on the side ipsilateral to injury.
      However, this effect is dependent on intact and uninjured pathways. In this study
      we utilized a cervical contusion injury model that more closely mimics the human
      condition. This injury model can determine the effectiveness of therapeutic
      interventions, in this case theophylline, on the isolated contused pathways of
      the spinal cord. Three weeks after a 150 kD C3/4 unilateral contusion subjects
      received a 15 mg/kg dose of theophylline prior to a contralateral C2 hemisection.
      Subjects that received theophylline were able to effectively utilize damaged
      pathways to breathe for up to 2 min, while subjects treated with saline were
      unable to support ventilation. Through these experiments, we demonstrate that
      theophylline can make injured pathways that mediate breathing more effective and
      therefore, suggest a potential therapeutic role in the critical time points
      immediately after injury.

PMID- 25979116
TI  - Syphilis testing in antenatal care: Policies and practices among laboratories in
      the Americas.
AB  - OBJECTIVE: To asses laboratory syphilis testing policies and practices among
      laboratories in the Americas. METHODS: Laboratory directors or designees from
      PAHO member countries were invited to participate in a structured, electronically
      delivered survey between March and August, 2014. Data on syphilis tests,
      algorithms, and quality control (QC) practices were analyzed, focusing on
      laboratories receiving specimens from antenatal clinics (ANCs). RESULTS: Surveys
      were completed by 69 laboratories representing 30 (86%) countries. Participating
      laboratories included 36 (52%) national or regional reference labs and 33 (48%)
      lower-level laboratories. Most (94%) were public sector facilities and 71%
      reported existence of a national algorithm for syphilis testing in pregnancy,
      usually involving both treponemal and non-treponemal testing (72%). Less than
      half (41%) used rapid syphilis tests (RSTs); and only seven laboratories
      representing five countries reported RSTs were included in the national algorithm
      for pregnant women. Most (83%) laboratories serving ANCs reported using some type
      of QC system; 68% of laboratories reported participation in external QC. Only 36%
      of laboratories reported data to national/local surveillance. Half of all
      laboratories serving ANC settings reported a stockout of one or more essential
      supplies during the previous year (median duration, 30days). CONCLUSION: Updating
      laboratory algorithms, improving testing standards, integrating data into
      existing surveillance, and improved procurement and distribution of commodities
      may be needed to ensure elimination of MTCT of syphilis in the Americas.

PMID- 25979117
TI  - Risk factors for stillbirths in Tete, Mozambique.
AB  - OBJECTIVE: To evaluate known risk factors for stillbirth and identify local
      priorities for stillbirth prevention among institutional deliveries in Tete,
      Mozambique. METHODS: A case-control study was conducted among 150 women who
      experienced stillbirths and 300 women who experienced live deliveries at three
      health facilities between December 1, 2009, and April 30, 2011. Case and control
      individuals were matched for health facility, age, and parity. Sociodemographic,
      pregnancy, and delivery characteristics (including HIV and syphilis serology)
      were assessed. Bivariate associations and a conditional logistic regression model
      identified variables contributing to fetal outcome. RESULTS: No between-group
      differences were recorded in the frequency of infection with HIV (25 [16.7%]
      cases vs 55 [18.3%] controls; P=0.663) or syphilis (6 [4.0%] vs 16 [5.3%];
      P=0.536) at delivery. Multivariate analysis revealed that stillbirth was
      associated with direct obstetric complications (mutually adjusted odds ratio [OR]
      6.7; 95% confidence interval [CI] 3.6-12.1), low socioeconomic status (mutually
      adjusted OR 1.8; 95% CI 1.1-3.1), and referral during childbirth (mutually
      adjusted OR 3.2; 95% CI 1.7-6.1). CONCLUSION: Stillbirths in Tete, Mozambique,
      were predominantly caused by direct obstetric complications requiring referral
      among women of low socioeconomic status. Prenatal management of HIV and syphilis
      limited effects on fetal outcome. Emergency obstetric care and referral systems
      should be the focus of interventions aimed at stillbirth prevention.

PMID- 25979118
TI  - Magnitude of maternal and neonatal mortality in Tanzania: A systematic review.
AB  - BACKGROUND: Maternal and neonatal mortality remains a serious challenge in
      Tanzania. Progress is tracked through maternal mortality ratios (MMR) and
      neonatal mortality rates (NMR), yet robust national data on these outcomes is
      difficult and expensive to ascertain, and mask wide variation. SEARCH STRATEGY:
      We searched EMBASE, MEDLINE, Popline, and EBSCO online databases, basing search
      terms on ("maternal" OR "neonatal") AND ("mortality" OR "cause of death") AND
      "Tanzania." SELECTION CRITERIA: Nationally representative or population
      representative from the subnational context were eligible, providing NMR, MMR, or
      numbers of maternal deaths or early neonatal deaths or neonatal deaths and live
      births. DATA COLLECTION AND ANALYSIS: Data were extracted on study context, time
      period, number of deaths and live births, definition of maternal and neonatal
      death, study design, and completeness and representativeness of data. NMR and MMR
      were extracted or calculated and study quality was assessed. Nationally
      representative data were compared with modelled national data from international
      agencies. MAIN RESULTS: 2107 records were screened yielding 21 maternal mortality
      and 15 neonatal mortality datasets. There were high mortality levels with wide
      subnational MMR and NMR variation. National survey data differed from the
      modelled estimates, with wide uncertainty ranges. CONCLUSION: Subnational data
      quality was generally poor with no observable trends and geographical clustering
      across several regions. Combined MMR and NMR reporting is uncommon. Modelled
      national estimates lack precision and are complex to interpret. Results suggest
      that aggregate national data are inadequate for policy generation and progress
      monitoring. We recommend strengthening of vital registration and Health
      Management Information Systems with complementary use of process indicators, for
      improved monitoring of, and accountability for maternal and newborn health.

PMID- 25979119
TI  - Quite an Accomplishment!

PMID- 25979120
TI  - CT and MRI manifestations of luxatio erecta humeri and a review of the
      literature.
AB  - AIM: We aimed to study luxatio erecta humeri using advanced imaging modalities.
      METHOD: Patients with luxatio erecta humeri and a subsequent magnetic resonance
      imaging (MRI) and/or computed tomography (CT) scan were included in this study.
      RESULTS: Among 10 identified cases, we detected 2 rotator cuff, 4 labral, and 2
      inferior glenohumeral ligament tears as well as 2 glenohumeral cartilage defects.
      We observed six comminuted displaced greater tuberosity fractures, four anterior
      inferior glenoid fractures, and four impaction fractures of humeral head.
      CONCLUSION: This study provides detailed radiologic findings associated with
      luxatio erecta humeri using MRI and CT.

PMID- 25979121
TI  - Universal scaling for the dilemma strength in evolutionary games.
AB  - Why would natural selection favor the prevalence of cooperation within the groups
      of selfish individuals? A fruitful framework to address this question is
      evolutionary game theory, the essence of which is captured in the so-called
      social dilemmas. Such dilemmas have sparked the development of a variety of
      mathematical approaches to assess the conditions under which cooperation evolves.
      Furthermore, borrowing from statistical physics and network science, the research
      of the evolutionary game dynamics has been enriched with phenomena such as
      pattern formation, equilibrium selection, and self-organization. Numerous
      advances in understanding the evolution of cooperative behavior over the last few
      decades have recently been distilled into five reciprocity mechanisms: direct
      reciprocity, indirect reciprocity, kin selection, group selection, and network
      reciprocity. However, when social viscosity is introduced into a population via
      any of the reciprocity mechanisms, the existing scaling parameters for the
      dilemma strength do not yield a unique answer as to how the evolutionary dynamics
      should unfold. Motivated by this problem, we review the developments that led to
      the present state of affairs, highlight the accompanying pitfalls, and propose
      new universal scaling parameters for the dilemma strength. We prove universality
      by showing that the conditions for an ESS and the expressions for the internal
      equilibriums in an infinite, well-mixed population subjected to any of the five
      reciprocity mechanisms depend only on the new scaling parameters. A similar
      result is shown to hold for the fixation probability of the different strategies
      in a finite, well-mixed population. Furthermore, by means of numerical
      simulations, the same scaling parameters are shown to be effective even if the
      evolution of cooperation is considered on the spatial networks (with the
      exception of highly heterogeneous setups). We close the discussion by suggesting
      promising directions for future research including (i) how to handle the dilemma
      strength in the context of co-evolution and (ii) where to seek opportunities for
      applying the game theoretical approach with meaningful impact. 

PMID- 25979122
TI  - Instruments, conductors, dancers, and intendants: Reply to comments on "The
      quartet theory of human emotions: An integrative and neurofunctional model".

PMID- 25979123
TI  - Protein-poly(amino acid) precipitation stabilizes a therapeutic protein l
      asparaginase against physicochemical stress.
AB  - Long-term storage in aqueous solution has been demanded for the practical
      application of therapeutic proteins. Recently, a precipitation-redissolution
      method was proposed to prepare salt-dissociable protein-polyelectrolyte complex
      (PPC). To elucidate the utility of the complex for storage of proteins, we
      investigated the stress tolerance of PPC precipitates containing l-asparaginase
      (ASNase) and poly-l-lysine (polyK). PPC precipitate containing ASNase and polyK
      was prepared by precipitation-redissolution method. The sample was treated to
      three types of stress, i.e., heat, shaking, and oxidation. The protein
      concentration, enzyme activity, and CD spectrum of the supernatants of samples
      were measured after stressed. PPC precipitate consisting of ASNase and polyK
      showed tolerance against thermal and shaking stress compared to the native
      solution. In addition, PPC precipitate protected ASNase from inactivation by
      oxidation. PPC precipitate of ASNase/polyK complex successfully stabilized ASNase
      against physicochemical stresses. These results suggest that the PPC precipitate
      has great potential as a storage method in aqueous solution for unstable
      proteins.

PMID- 25979124
TI  - Filling the knowledge gaps.

PMID- 25979125
TI  - Filling a niche market: administering drugs by injection or infusion.
AB  - There is greater incentive than ever to keep individuals requiring injectable or
      infusion therapy in the nursing facility-and not transfer them to a hospital-to
      receive those services. There is a demand for pharmacists with the skills,
      knowledge, and training to provide these services. To make that possible,
      pharmacies and pharmacists with the proper equipment, supplies, knowledge,
      training, and expertise are needed to work closely with physicians and nurses to
      provide sterile, properly compounded products and ensure that drugs are
      administered appropriately and in the right doses. These pharmacists also can
      work with facilities and practitioners to assess, improve, and document quality. 

PMID- 25979126
TI  - Managing acute coronary syndromes in the elderly.
AB  - OBJECTIVE: To provide an up-to-date review of the available evidence regarding
      treatment of acute coronary syndromes (ACS) in elderly patients. DATA SOURCE: A
      PubMed search of articles published through January 2015 was done using a
      combination of the following words: acute coronary syndrome, pharmacy, elderly,
      geriatric, myocardial infarction, beta-blocker, statin, antiplatelet,
      antithrombin, angiotensin-converting enzyme inhibitor, and aspirin. STUDY
      SELECTION/DATA EXTRACTION: Relevant original research, review articles, and
      guidelines were assessed for the management of elderly patients with ACS.
      References from the above literature were also evaluated. Articles were selected
      for inclusion based on relevance to the topic, detailed methods, and complete
      results. DATA SYNTHESIS: Because of the high prevalence of ACS in elderly
      patients, appropriate treatment is necessary to reduce morbidity and mortality;
      however, these patients are often under-represented in trials. This article
      provides a review of the current literature on treatment of ACS in the elderly
      and provides guidance to pharmacists regarding optimal pharmacotherapy for these
      patients. CONCLUSION: Appropriate treatment of ACS can help improve outcomes in
      elderly patients, and the pharmacist can provide guidance regarding evidence
      based therapy.

PMID- 25979127
TI  - Discontinuation of memantine standard release and its impact on patient therapy.
AB  - The recently announced discontinuation of Namenda (memantine HCl) and consequent
      shortage of Namenda XR (memantine HCl extended-release) is a matter that affects
      physicians, patients with Alzheimer's disease, caregivers, and consultant
      pharmacists. The manufacturer's announcement to discontinue standard-release
      product came eight months after the extended-release formulation became available
      in June 2013. The manufacturer planned to discontinue the standard-release
      tablets to focus on XR capsules by August 2014, giving patients and their
      caregivers-who prefer immediate-release formulations-no other options except the
      oral solution formulation. This article updates pharmacists with the current
      development on the various pharmacy and therapeutic issues on memantine products.
      Consultant pharmacists play an important role in educating prescribers and
      caregivers of the recent changes on this matter. They shall help to ensure proper
      dosage switching among various formulations. Consultant pharmacists can also help
      caregivers to identify the most cost-effective options when generic memantine
      becomes available in the future. 

PMID- 25979128
TI  - Is it time to call it quits on low-dose quetiapine?
AB  - The mandate of the Centers for Medicare & Medicaid Services to decrease the use
      of antipsychotics in long-term care facilities requires creative solutions. Low
      dose quetiapine is used for a multitude of behavioral disorders and sleep
      problems in the nursing facility population. Yet, at doses of 25 mg per day or
      less, it doesn't have strong affinity (if any) for the dopamine-2 (D2) receptor,
      but it does maintain affinity for the histamine-1 and alpha-1 receptors. This
      begs the question: If it's not antagonizing the D2 receptor, could the use of
      something with similar receptor-affinity produce the same result, allowing
      discontinuation of the antipsychotic altogether? Using knowledge of receptor
      affinities and the pharmacologic action of low-dose quetiapine, consultant
      pharmacists may have one additional tool in their armamentarium of fighting
      inappropriate antipsychotic use. 

PMID- 25979129
TI  - An Analysis and Comparison of Medication Therapy Management Cost-Avoidance vs.
      Fee-for-Service Financial Models.
AB  - OBJECTIVE: To describe, compare, and contrast cost-avoidance and fee-for-service
      medication therapy management (MTM) financial models of practice to allow
      clinicians to better choose the type of MTM practice that best fits their
      particular practice environment. DATA SOURCES: Literature regarding pharmacist
      practices providing MTM services and capstone projects of proposed and currently
      operating MTM pharmacist practices presented in the University of Florida Master
      of Science MTM program. STUDY AND SOURCE SELECTION: Understanding the two major
      payment methods of sustaining a financially viable MTM pharmacist practice is
      critical to practice success. Survey was broad with regard to clinical models to
      compare differences because funding to support these services can be difficult to
      obtain. DATA SYNTHESIS: Despite differences in approach, various methods exist to
      financially sustain a pharmacist with an MTM practice. Each method or model has
      advantages and disadvantages in differing practice environments. CONCLUSION: With
      enough cost avoidance or revenue generation, financially dissimilar MTM financial
      models can be sustainable.

PMID- 25979130
TI  - Bill introduced in the Senate to Preserve Six Protected classes of drugs.

PMID- 25979131
TI  - Case reports of synthetic cannabinoid XLR-11 associated fatalities.
AB  - Synthetic cannabinoids have been available in herbal incense and potpourri
      products over the Internet and in smoke shops for the last several years. We
      report the deaths of two individuals that were associated with XLR-11. Specimens
      were extracted via a liquid-liquid extraction at basic pH into hexane:ethyl
      acetate and analyzed by liquid chromatography tandem mass spectrometry. For these
      two case reports, we describe the instrumental analysis and extraction methods
      for XLR-11, toxicological results for postmortem blood specimens, relevant case
      information and autopsy findings. We also briefly review any previously published
      peer-reviewed reports in which XLR-11 was analytically confirmed and determined
      to be an intoxicating agent. 

PMID- 25979132
TI  - Regarding giant submandibular gland mucoceles.

PMID- 25979133
TI  - Positioning a public health framework at the intersection of child maltreatment
      and intimate partner violence: Primary prevention requires working outside
      existing systems.

PMID- 25979134
TI  - The right to childhood: Reflections on the 2014 Nobel Peace Prize.

PMID- 25979135
TI  - A Brief Intervention Facilitates Discussions About Discipline in Pediatric
      Primary Care.
AB  - BACKGROUND: Participants were consecutive English or Spanish speaking parents of
      1- to 5-year-old children presenting for a well-child visit. Parents viewed a 5-
      to 10-minute intervention that teaches appropriate discipline strategies. The
      participation rate was 99% (129/130). Thirty-six percent (46/129) reported they
      had a discussion about discipline with their pediatrician. Of the parents who had
      a discussion, 93% (43/46) agreed or strongly agreed that the intervention program
      helped with a discussion about discipline. One hundred percent (19/19) of
      Hispanic parents reported that the program was helpful compared with 86% (12/14)
      of Black parents and 91% (10/11) of White parents. Parents' qualitative responses
      revealed that the intervention helped by facilitating communication with their
      physician and/or by providing information. Brief interventions, integrated into
      the primary care visit can help parents have discussions about discipline with
      their physician. The results have implications for improving pediatric primary
      care services, violence prevention, and child abuse prevention.

PMID- 25979136
TI  - Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for
      rectal administration of flurbiprofen with improved bioavailability and reduced
      initial burst effect.
AB  - The purpose of this study was to develop novel solid lipid nanoparticle (SLN)
      loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of
      flurbiprofen with improved bioavailability and reduced initial burst effect. The
      flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after
      optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2
      weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN
      composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was
      a solid at room temperature, and changed to liquid form at physiological
      temperature due to its melting point of about 32 degrees C. This SLN gave the
      mean particle size of about 190nm and entrapment efficiency of around 90%. The
      DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in
      various poloxamer solutions. Their rheological characterisation, release and
      stability were investigated while a morphological and pharmacokinetic study was
      performed after its rectal administration to rats compared with the drug and
      hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation
      time, but increased the viscosity at 25 degrees C, gel strength and mucoadhesive
      force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188
      (10%/15%/25%)] with the gelation temperature of about 35 degrees C existed as
      liquid at room temperature, but gelled at 30-36 degrees C, leading to opposite
      reversible property of SLN. Thus, it was easy to administer rectally, and it
      gelled rapidly inside the body. This DRTH gave a significantly increased
      dissolution rate of the drug as compared to the flurbiprofen, but significantly
      retarded as compared to the hydrogel, including the initial dissolution rate.
      Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold
      AUC values compared to the drug, and lower initial plasma concentration and Cmax
      value compared to the hydrogel due to reduced initial burst effect. No damage in
      rectal mucosa was observed after the application of DRTH. Thus, this DRTH system
      with improved bioavailability and reduced initial burst effect would be
      recommended as an alternative for the flurbiprofen-loaded rectal pharmaceutical
      products. 

PMID- 25979137
TI  - Cardiac magnetic resonance imaging and electrophysiology "the beauty is in the
      eye of the beholder".

PMID- 25979138
TI  - TAS-102 prolongs overall survival in refractory colorectal cancer, study shows.

PMID- 25979139
TI  - Editorial for the special issue on Ganoderma.

PMID- 25979140
TI  - Reinforcement learning in depression: A review of computational research.
AB  - Despite being considered primarily a mood disorder, major depressive disorder
      (MDD) is characterized by cognitive and decision making deficits. Recent research
      has employed computational models of reinforcement learning (RL) to address these
      deficits. The computational approach has the advantage in making explicit
      predictions about learning and behavior, specifying the process parameters of RL,
      differentiating between model-free and model-based RL, and the computational
      model-based functional magnetic resonance imaging and electroencephalography.
      With these merits there has been an emerging field of computational psychiatry
      and here we review specific studies that focused on MDD. Considerable evidence
      suggests that MDD is associated with impaired brain signals of reward prediction
      error and expected value ('wanting'), decreased reward sensitivity ('liking')
      and/or learning (be it model-free or model-based), etc., although the causality
      remains unclear. These parameters may serve as valuable intermediate phenotypes
      of MDD, linking general clinical symptoms to underlying molecular dysfunctions.
      We believe future computational research at clinical, systems, and
      cellular/molecular/genetic levels will propel us toward a better understanding of
      the disease. 

PMID- 25979141
TI  - Altered visual perception near the hands: A critical review of attentional and
      neurophysiological models.
AB  - Visual perception changes as a function of hand proximity. While various
      theoretical accounts have been offered for this alteration (attentional
      prioritisation, bimodal cell involvement, detailed evaluation, and magnocellular
      neuron input enhancement), the current literature lacks consensus on these
      mechanisms. The purpose of this review, therefore, is to critically review the
      existing body of literature in light of these distinct theoretical accounts. We
      find that a growing number of results support the magnocellular (M-cell)
      enhancement account, and are difficult to reconcile with general attention-based
      explanations. Despite this key theoretical development in the field, there has
      been some ambiguity with interpretations offered in recent papers, for example,
      equating the existing attentional and M-cell based explanations, when in fact
      they make contrasting predictions. We therefore highlight the differential
      predictions arising from the distinct theoretical accounts. Importantly, however,
      we also offer novel perspectives that synthesises the role of attention and
      neurophysiological mechanisms in understanding altered visual perception near the
      hands. We envisage that this theoretical development will ensure that the field
      can progress from documenting behavioural differences, to a consensus on the
      underlying visual and neurophysiological mechanisms. 

PMID- 25979142
TI  - Unraveling the modulatory actions of serotonin on male rat sexual responses.
AB  - Animal studies and clinical investigations reveal that serotonin plays a central
      role in the control of the ejaculatory threshold. The chronic use of selective
      serotonin reuptake inhibitors (SSRIs) frequently results in sexual dysfunction,
      inviting to analyze the modulatory actions of serotonin on male sexual function
      in depth. Even though the main effect of serotonin on male sexual responses is
      inhibitory, this neuromodulator also mediates brief important stimulatory
      actions. Serotonin (5-HT) can activate two intracellular signaling pathways: a
      lower-threshold facilitatory pathway, and a higher-threshold inhibitory pathway,
      leading to biphasic effects. We propose that these divergent actions are related
      to the stimulation or inhibition of glutamatergic and GABAergic interneurons.
      Experimental evidence suggests that low 5-HT concentrations produce stimulatory
      actions on male ejaculatory aspects that might be mediated by the blockade of the
      GABAergic neurotransmission in the MPOA and spinal cord, which in turn releases a
      tonic inhibition that allows other neurotransmitters such as glutamate,
      noradrenaline, oxytocin and dopamine to initiate a sequence of molecular events
      resulting in the expression of ejaculation. Similar serotonin actions, mediated
      via interneurons, have been proposed for the regulation of other processes and
      occur in many central nervous system areas, indicating that it is not an isolated
      phenomenon. 

PMID- 25979144
TI  - A guide to the Interventional Radiology residency program requirements.
AB  - The program requirements for the new Interventional Radiology (IR) Residency were
      approved by the ACGME in September 2014. Soon, training institutions will be able
      to apply for accreditation and begin enrolling residents. The IR program
      requirements are long (44 pages) and a bit complex. In addition, some concepts in
      the program requirements, such as options for integrated or independent formats,
      may be unfamiliar to the radiology community. In this article, we summarize key
      concepts and explain important provisions in the IR program requirements. We hope
      to provide the reader with a firm foundation for understanding the full program
      requirement document and the application process. 

PMID- 25979143
TI  - The Challenges of Resolving a Rapid, Recent Radiation: Empirical and Simulated
      Phylogenomics of Philippine Shrews.
AB  - Phylogenetic relationships in recent, rapid radiations can be difficult to
      resolve due to incomplete lineage sorting and reliance on genetic markers that
      evolve slowly relative to the rate of speciation. By incorporating hundreds to
      thousands of unlinked loci, phylogenomic analyses have the potential to mitigate
      these difficulties. Here, we attempt to resolve phylogenetic relationships among
      eight shrew species (genus Crocidura) from the Philippines, a phylogenetic
      problem that has proven intractable with small (< 10 loci) data sets. We
      sequenced hundreds of ultraconserved elements and whole mitochondrial genomes in
      these species and estimated phylogenies using concatenation, summary coalescent,
      and hierarchical coalescent methods. The concatenated approach recovered a
      maximally supported and fully resolved tree. In contrast, the coalescent-based
      approaches produced similar topologies, but each had several poorly supported
      nodes. Using simulations, we demonstrate that the concatenated tree could be
      positively misleading. Our simulations also show that the tree shape we tend to
      infer, which involves a series of short internal branches, is difficult to
      resolve, even if substitution models are known and multiple individuals per
      species are sampled. As such, the low support we obtained for backbone
      relationships in our coalescent-based inferences reflects a real and appropriate
      lack of certainty. Our results illuminate the challenges of estimating a
      bifurcating tree in a rapid and recent radiation, providing a rare empirical
      example of a nearly simultaneous series of speciation events in a terrestrial
      animal lineage as it spreads across an oceanic archipelago.

PMID- 25979145
TI  - Enriched Audience Engagement Through Twitter: Should More Academic Radiology
      Departments Seize the Opportunity?
AB  - PURPOSE: The aim of this study was to evaluate use of the microblogging social
      network Twitter by academic radiology departments (ARDs) in the United States.
      METHODS: Twitter was searched to identify all accounts corresponding with United
      States ARDs. All original tweets from identified accounts over a recent 3-month
      period (August to October 2014) were archived. Measures of account activity, as
      well as tweet and link content, were summarized. RESULTS: Fifteen ARDs (8.2%) had
      Twitter accounts. Ten (5.5%) had "active" accounts, with >=1 tweet over the 3
      month period. Active accounts averaged 711 +/- 925 followers (maximum, 2,885) and
      61 +/- 93 tweets (maximum, 260) during the period. Among 612 tweets from active
      accounts, content most commonly related to radiology-related education (138),
      dissemination of departmental research (102), general departmental or hospital
      promotional material (62), departmental awards or accomplishments (60), upcoming
      departmental lectures (59), other hospital-related news (55), medical advice or
      information for patients (38), local community events or news (29), social media
      and medicine (27), and new departmental or hospital hires or expansion (19).
      Eighty percent of tweets (490 of 612) included 315 unique external links. Most
      frequent categories of link sources were picture-, video-, and music-sharing
      websites (89); the ARD's website or blog (83); peer-reviewed journal articles
      (40); the hospital's or university's website (34), the lay press (28), and
      Facebook (14). CONCLUSIONS: Twitter provides ARDs the opportunity to engage their
      own staff members, the radiology community, the department's hospital, and
      patients, through a broad array of content. ARDs frequently used Twitter for
      promotional and educational purposes. Because only a small fraction of ARDs
      actively use Twitter, more departments are encouraged to take advantage of this
      emerging communication tool.

PMID- 25979146
TI  - Comparison of Blood Flow in Branched and Fenestrated Stent-Grafts for
      Endovascular Repair of Abdominal Aortic Aneurysms.
AB  - PURPOSE: To report a computational study assessing the hemodynamic outcomes of
      branched stent-grafts (BSGs) for different anatomic variations. METHODS:
      Idealized models of BSGs and fenestrated stent-grafts (FSGs) were constructed
      with different visceral takeoff angles (ToA) and lateral aortic neck angles. ToA
      was defined as the angle between the centerlines of the main stent-graft and side
      branch, with 90 degrees  representing normal alignment, and 30 degrees  and 120
      degrees  representing angulated side branches. Computational simulations were
      performed by solving the conservation equations governing the blood flow under
      physiologically realistic conditions. RESULTS: The largest renal flow
      recirculation zones (FRZs) were observed in FSGs at a ToA of 30 degrees , and the
      smallest FRZ was also found in FSGs (at a ToA of 120 degrees ). For straight-neck
      stent-grafts with a ToA of 90 degrees , mean flow in each renal artery was 0.54,
      0.46, and 0.62 L/min in antegrade BSGs, retrograde BSGs, and FSGs, respectively.
      For angulated stent-grafts, the corresponding values were 0.53, 0.48, and 0.63
      L/min. All straight-neck stent-grafts experienced equal cycle-averaged
      displacement forces of 1.25, 1.69, and 1.95 N at ToAs of 30 degrees , 90 degrees
      , and 120 degrees , respectively. Angulated main stent-grafts experienced an
      equal cycle-averaged displacement force of 3.6 N. CONCLUSION: The blood flow rate
      in renal arteries depends on the configuration of the stent-graft, with an FSG
      giving maximum renal flow and a retrograde BSG resulting in minimum renal flow.
      Nevertheless, the difference was small, up to 0.09 L/min. Displacement forces
      exerted on stent-grafts are very sensitive to lateral neck angle but not on the
      configuration of the stent-graft.

PMID- 25979147
TI  - [Morphological and molecular characterization of isolates of Macrophomina
      phaseolina associated with sugarcane in Mexico].
AB  - Charcoal rot caused by Macrophomina phaseolina is an important disease of
      sugarcane in Mexico. This study was carried out to characterize isolates of M.
      phaseolina obtained from sugarcane by the combination of morphological and
      molecular analyses. The morphological characterization of 10 isolates was
      performed using scanning electron microscopy and light microscopy. To confirm the
      morphological identification, rDNA from two representative isolates was
      extracted, and the internal transcribed spacer (ITS) region was amplified by
      polymerase chain reaction and sequenced using specific primers MpKF1 and MpKR1.
      Based on their morphological characteristics, all isolates were identified as M.
      phaseolina. Moreover, the analysis of two ITS sequences showed 100% similarity
      with the M. phaseolina sequences deposited in the GenBank. To our knowledge, this
      is the first study in the world aimed at characterizing isolates of M. phaseolina
      obtained from sugarcane. 

PMID- 25979148
TI  - Nuclear acridine orange fluorescence in Rhizoctonia isolates from rice.

PMID- 25979149
TI  - Adjustment of a rapid method for quantification of Fusarium spp. spore
      suspensions in plant pathology.
AB  - The use of a Neubauer chamber is a broadly employed method when cell suspensions
      need to be quantified. However, this technique may take a long time and needs
      trained personnel. Spectrophotometry has proved to be a rapid, simple and
      accurate method to estimate the concentration of spore suspensions of isolates of
      the genus Fusarium. In this work we present a linear formula to relate absorbance
      measurements at 530nm with the number of microconidia/ml in a suspension. 

PMID- 25979150
TI  - Evaluation of an intervention to reduce tidal volumes in ventilated ICU patients.
AB  - BACKGROUND: There is considerable evidence that the use of tidal volumes <6 ml
      kg(-1) predicted body weight (PBW) reduces mortality in mechanically ventilated
      patients. We evaluated the effectiveness of using a large screen displaying
      delivered tidal volume in ml kg(-1) (PBW) for reducing tidal volumes. METHODS: We
      assessed the intervention in two 6-month periods. A qualitative study was
      undertaken after the intervention period to examine staff interaction with the
      intervention. The study was conducted in a mixed medical and surgical intensive
      care unit at University Hospitals Bristol, UK. Consecutive patients requiring
      controlled mechanical ventilation for more than 1 h were included. Alerts were
      triggered when tidal volume breached predetermined targets and these alerts were
      visible to ICU clinicians in real time. RESULTS: A total of 199 patients with
      7640 h of data were observed during the control time period and 249 patients with
      10 656 h of data were observed in the intervention period. Time spent with tidal
      volumes <6 ml kg(-1) PBW increased from 17.5 to 28.6% of the period of controlled
      mechanical ventilation. Time spent with a tidal volume <8 ml kg(-1) PBW increased
      from 60.6 to 73.9%. The screens were acceptable to staff and stimulated an
      increase in attendance of clinicians at the bedside to adjust ventilators.
      CONCLUSIONS: Changing the format of data and displaying it with real-time alerts
      reduced delivered tidal volumes. Configuring information in a format more likely
      to result in desired outcomes has the potential to improve the translation of
      evidence into practice.

PMID- 25979151
TI  - Temperature-responsive polymeric nanospheres containing methotrexate and gold
      nanoparticles: A multi-drug system for theranostic in rheumatoid arthritis.
AB  - Inflammation plays a crucial role in rheumatoid arthritis progress. In the
      present work, a novel stealth polymeric nanospheres platform able to carry anti
      inflammatory drugs and an imaging agent was developed. Incorporation of gold
      nanoparticles will allow photoacoustic imaging and near infra-red photothermal
      application. Through emulsion-diffusion evaporation technique methotrexate and
      gold nanoparticles were incorporated in the pegylated-poly(DL-lactic-co-glycolic
      acid) nanospheres. In vitro drug release assays revealed pH and temperature
      dependence on gold nanoparticles. Blank nanospheres exhibited negligible in vitro
      cytotoxicity, while methotrexate-loaded nanospheres hampered monocytes and
      macrophages viability at a higher level than free methotrexate. Confocal
      fluorescent microscopy and flow cytometry revealed effective nanospheres
      internalization, and that their cellular uptake was energy dependent mediated by
      caveolae and clathrin-endocytosis mechanism. Finally, MTX-loaded multifunctional
      nanospheres containing gold lead to a significant reduction of IL-1beta, IL-6 and
      TNF-alpha inflammatory cytokines produced by monocytes and macrophages upon in
      vitro inflammatory stimulation, suggesting a favorable anti-inflammatory
      activity. These results confirm that the multifunctional nanospheres represent a
      promising theranostic platform for RA diagnosis and intracellular treatment, by
      combining methotrexate and gold nanoparticles for a highly effective targeted
      chemo-photothermal therapy.

PMID- 25979152
TI  - Clinical placements in Australian general practice: (Part 1) the experiences of
      pre-registration nursing students.
AB  - An international shift towards strengthening primary care services has stimulated
      the growth of nursing in general (family) practice. As learning in the clinical
      setting comprises a core component of pre-registration nursing education, it is
      logical that clinical placement opportunities would follow the workforce growth
      in this setting. Beyond simply offering placements in relevant clinical areas, it
      is vital to ensure high quality learning experiences that meet the educational
      needs of pre-registration nurses. Part 1 of a two part series reports on the
      qualitative study of a mixed methods project. Fifteen pre-registration nursing
      students participated in semi-structured interviews following a clinical
      placement in an Australian general practice. Interviews were transcribed verbatim
      and underwent a process of thematic analysis. Findings are presented in the
      following four themes; (1) Knowledge of the practice nurse role: I had very
      limited understanding, (2) Quality of the learning experience: It was a fantastic
      placement, (3) Support, belonging and mutual respect: I really felt part of the
      team, (4) Employment prospects: I would really, really love to go to a general
      practice but ...... General practice placements exposed students to a diverse
      range of clinical skills which would equip them for future employment in primary
      care. Exposure to nursing in general practice also stimulated students to
      consider a future career in this clinical setting. 

PMID- 25979154
TI  - Desmoglein 3 and p40 immunoreactivity in neoplastic and nonneoplastic thymus: a
      potential adjunct to help resolve selected diagnostic and staging problems.
AB  - The potential usefulness of the squamous markers p40 and desmoglein 3 (DSG-3) for
      the diagnosis and staging of selected thymic lesions is uncertain. We
      investigated their expression and distribution pattern in 66 thymomas, 12 thymic
      squamous carcinomas, 6 undifferentiated thymic carcinomas, 5 hyperplastic thymi,
      and 5 normal thymi. p40 nuclear and DSG-3 cytoplasmic/membranous immunoreactivity
      in greater than or equal to 10% of thymic epithelial cells was interpreted as
      positive, and DSG-3 distribution pattern was classified as organotypic and
      nonorganotypic. All nonneoplastic thymic tissues, 100% of thymic squamous
      carcinomas, 97% of thymomas, and 50% of undifferentiated thymic carcinomas were
      positive for p40. Expression of p40 in almost all thymomas and in 50% of
      undifferentiated carcinomas that lacked squamous features suggests that p40 is
      not a good marker for the diagnosis of thymic squamous carcinoma. All normal and
      hyperplastic thymi, 51.5% of thymomas, and 0% of thymic squamous carcinomas
      expressed DSG-3 in an organotypic pattern, and 13.6% of thymomas and 83% of
      thymic squamous carcinomas were DSG-3 positive in a nonorganotypic pattern.
      Findings suggest that nonorganotypic DSG-3 expression favors the diagnosis of
      squamous cell carcinoma over thymoma. In 26 (60.5%) of the 43 cases where
      neoplastic and nonneoplastic thymus were present on the same slide, the
      presence/absence or distribution pattern of DSG-3 immunoreactivity was different
      in the 2 components, suggesting that this marker can be helpful in staging
      thymomas with incomplete encapsulation. The presence of DSG-3-positive and DSG-3
      negative thymomas raises the possibility that these tumors may originate from 2
      different types of thymic epithelial cells. 

PMID- 25979155
TI  - Division of the spinal accessory nerve in the anterior triangle: a prospective
      clinical study.
AB  - The anatomical relation between the spinal accessory nerve and internal jugular
      vein is well documented, but other variants of the nerve, including the
      contributions of the cervical plexus to supply motor fibres to the trapezius, are
      less well known. We have previously described an anatomical variant in which the
      spinal accessory nerve divided before entering the sternocleidomastoid, and the
      inferior trunk passed directly under it to supply the trapezius. We now present a
      prospective study of 133 neck dissections (excluding radical dissections) in
      which a meticulous search was made for the variant in the anterior triangle of
      the neck during operation. We found it in 3 necks (2%). One of the 3 patients had
      a bilateral neck dissection but it was found on one side only, and in 2 cases it
      communicated with the cervical plexus. In all 3, stimulation of the inferior
      division resulted in contraction of the trapezius while the upper division was
      found to supply the sternocleidomastoid only. The finding of this variant, which
      was more common than first thought, highlights the need for meticulous dissection
      of the nerve before it enters the sternocleidomastoid to ensure that, when
      present, the inferior branch is preserved to minimise potential postoperative
      shoulder dysfunction. Further research including a cadaveric study is needed to
      understand this important variant more fully. 

PMID- 25979153
TI  - Supporting information retrieval from electronic health records: A report of
      University of Michigan's nine-year experience in developing and using the
      Electronic Medical Record Search Engine (EMERSE).
AB  - OBJECTIVE: This paper describes the University of Michigan's nine-year experience
      in developing and using a full-text search engine designed to facilitate
      information retrieval (IR) from narrative documents stored in electronic health
      records (EHRs). The system, called the Electronic Medical Record Search Engine
      (EMERSE), functions similar to Google but is equipped with special
      functionalities for handling challenges unique to retrieving information from
      medical text. MATERIALS AND METHODS: Key features that distinguish EMERSE from
      general-purpose search engines are discussed, with an emphasis on functions
      crucial to (1) improving medical IR performance and (2) assuring search quality
      and results consistency regardless of users' medical background, stage of
      training, or level of technical expertise. RESULTS: Since its initial deployment,
      EMERSE has been enthusiastically embraced by clinicians, administrators, and
      clinical and translational researchers. To date, the system has been used in
      supporting more than 750 research projects yielding 80 peer-reviewed
      publications. In several evaluation studies, EMERSE demonstrated very high levels
      of sensitivity and specificity in addition to greatly improved chart review
      efficiency. DISCUSSION: Increased availability of electronic data in healthcare
      does not automatically warrant increased availability of information. The success
      of EMERSE at our institution illustrates that free-text EHR search engines can be
      a valuable tool to help practitioners and researchers retrieve information from
      EHRs more effectively and efficiently, enabling critical tasks such as patient
      case synthesis and research data abstraction. CONCLUSION: EMERSE, available free
      of charge for academic use, represents a state-of-the-art medical IR tool with
      proven effectiveness and user acceptance.

PMID- 25979156
TI  - Spatial and temporal resolutions of EEG: Is it really black and white? A scalp
      current density view.
AB  - Among the different brain imaging techniques, electroencephalography (EEG) is
      classically considered as having an excellent temporal resolution, but a poor
      spatial one. Here, we argue that the actual temporal resolution of conventional
      (scalp potentials) EEG is overestimated, and that volume conduction, the main
      cause of the poor spatial resolution of EEG, also distorts the recovered time
      course of the underlying sources at scalp level, and hence degrades the actual
      temporal resolution of EEG. While Current Source Density (CSD) estimates, through
      the Surface Laplacian (SL) computation, are well known to dramatically reduce
      volume conduction effects and hence improve EEG spatial resolution, its positive
      impact on EEG temporal resolution is much less recognized. In two simulation
      studies, we first show how volume conduction and reference electrodes distort the
      scalp potential time course, and how SL transform provides a much better spatio
      temporal description. We then exemplify similar effects on two empirical
      datasets. We show how the time courses of the scalp potentials mis-estimate the
      latencies of the relevant brain events and that CSD provides a much richer, and
      much more accurate, view of the spatio-temporal dynamics of brain activity. 

PMID- 25979157
TI  - A mechanism-oriented approach to psychopathology: The role of Pavlovian
      conditioning.
AB  - The Research Domain Criteria Project suggests to base the classification of
      mental disorders on dimensions of observable behavior and neurobiological
      measures of these functions rather than on symptom-based descriptive categorical
      diagnoses. We suggest a mechanistic approach that focuses on the role of learning
      as a core mechanism that can be studied in animals and humans. We review human
      studies on neurobiological, psychophysiological, and behavioral correlates of
      Pavlovian associative learning and delineate commonalities and differences across
      disorders. In addition to the hedonic value, the learning phase (i.e.
      habituation, acquisition, extinction, extinction recall), the role of stimulus
      properties (i.e., cue and context), and event timing (e.g. delay and trace
      conditioning) were considered. We address how core behavioral and
      psychophysiological indicators of conditioning, such as contingency ratings and
      skin conductance responses or startle modulation, respectively, are altered. We
      also discuss plastic changes in core brain regions and the interaction of brain
      regions in inhibitory and excitatory circuits. We also address the translation of
      findings pertaining to classical conditioning and its affiliated processes into
      the development of new behavioral and pharmacological treatments for mental
      disorders, and discuss productive avenues for future studies. 

PMID- 25979158
TI  - Reply to Letter: 'Can therapeutic hypothermia of 33 degrees C itself not modulate
      inflammatory response after out-of-hospital cardiac arrest?'.

PMID- 25979159
TI  - Can therapeutic hypothermia of 33 degrees C itself not modulate inflammatory
      response after out-of-hospital cardiac arrest?

PMID- 25979160
TI  - Quality of life and physical components linked to sarcopenia: The SarcoPhAge
      study.
AB  - INTRODUCTION: The SarcoPhAge project is an ongoing longitudinal study following
      community-dwelling elderly subjects with the objective to assess some health and
      functional consequences of sarcopenia. The sarcopenia diagnosis algorithm
      developed by the European Working Group on Sarcopenia in Older People (EWGSOP)
      and used in the present study needs further validation through cross-sectional
      and longitudinal studies. The aim of the present study is to assess, using this
      algorithm, the prevalence of sarcopenia and the clinical components linked to
      this geriatric syndrome. METHODS: Participants were community dwelling subjects
      aged 65years or older. To diagnose sarcopenia, we applied the definition of the
      EWGSOP. Muscle mass was measured by dual-energy X-ray absorptiometry, muscle
      strength by a hydraulic dynamometer and physical performance by the SPPB test.
      Large amounts of socio-demographic, anamnestic and clinical data were collected
      in all subjects. RESULTS OVER ONE YEAR: 534 subjects were recruited for this
      study (60.5% of women, mean age of 73.5+/-6.16years), among whom 73 subjects were
      diagnosed sarcopenic, which represents a global prevalence of 13.7%. Prevalence
      was 11.8% in men and 14.9% in women. Sarcopenic subjects were older; had a lower
      Body Mass Index, lower calf, waist, wrist and arm circumferences; presented more
      cognitive impairments (Mini-Mental State Examination), more comorbidities; were
      more often malnourished; and consumed more drugs. After adjustment for age, BMI,
      cognitive status, nutritional status, number of comorbidities and number of
      drugs, sarcopenic subjects had a worse physical health-related quality of life
      (SF-36) for the domain of physical functioning, were at higher risk of falls
      (Timed Up and Go test), were more frail (Fried), presented more often tiredness
      for the achievement of activities of daily living (Mobility-test), presented less
      fat mass and obviously less lean mass. Sarcopenic women were also more dependent
      for housekeeping and handling finances (Lawton scale) than non-sarcopenic ones.
      CONCLUSION: Sarcopenia seems to be associated with many harmful clinical
      components making this geriatric syndrome a real public health burden. Follow-up
      data of the SarcoPhAge study will be helpful to assess the outcomes of sarcopenia
      based on the EWGSOP diagnosis algorithm and its different proposed cut-offs.

PMID- 25979161
TI  - Transmembrane protein 64 reciprocally regulates osteoblast and adipocyte
      differentiation by modulating Wnt/beta-catenin signaling.
AB  - Age-related osteoporosis is associated with a reciprocal decrease in bone
      formation and an increase in adiposity in the bone marrow niche. We previously
      reported Transmembrane protein 64 (Tmem64) to be an important regulator of
      osteoclast function; however, its precise role in osteoblasts has not yet been
      established. Here, we showed that ablation of the Tmem64 gene in mice resulted in
      markedly increased osteoblast and reduced adipocyte differentiation from bone
      marrow-derived stromal cells (BMSCs). Conversely, Tmem64 overexpression inhibited
      osteogenesis and accelerated adipogenesis. Furthermore, BMSCs isolated from
      Tmem64 knockout mice formed a greater number of colony-forming unit-osteoblasts
      and a lower number of colony-forming unit-adipocytes than the wild type controls.
      Mechanistically, the expression level of beta-catenin, the key Wnt signaling
      molecule, increased significantly, and its nuclear translocation was enhanced in
      Tmem64-deficient cells. Introduction of Tmem64 significantly suppressed beta
      catenin-mediated transcriptional activity in an in vitro co-transfection
      experiment as well as during an in vivo experiment involving BAT-Gal reporter
      mice. These results demonstrate that Tmem64 plays an important role in the
      regulation of mesenchymal lineage allocation by modulating Wnt/beta-catenin
      signaling. 

PMID- 25979162
TI  - Feasibility of Measuring Ventilatory Threshold in Adults With Stroke-Induced
      Hemiparesis: Implications for Exercise Prescription.
AB  - OBJECTIVES: To assess the feasibility of measuring ventilatory threshold (VT) in
      adults with walking impairments due to stroke. Secondary objectives are to assess
      reliability of VT over trials; assess whether participants could sustain
      treadmill walking at VT; and compare mean heart rate during sustained treadmill
      walking to estimated heart rate reserve (HRR). DESIGN: Cross-sectional, single
      group design. SETTING: University research laboratory. PARTICIPANTS: Volunteer
      sample of adults (N=8) with impaired walking resulting from chronic stroke.
      INTERVENTIONS: Three submaximal treadmill walking tests on 3 separate days; a 30
      minute treadmill walking session on a fourth day. MAIN OUTCOME MEASURES: Gas
      exchange variables were measured, and 2 independent observers identified VT. Mean
      heart rate response to treadmill walking at VT was measured and compared with
      estimated 40% of HRR. RESULTS: VT was measured successfully in 88% of all trials.
      There was no difference in VT among trials (P=.17). After multiple imputations to
      account for 3 missing data points, the intraclass correlation coefficient was .87
      (95% confidence interval, .80-.95). All participants were able to walk for 20
      minutes at VT. Mean +/- SD heart rate during the session was 66.0%+/-8.0% of
      estimated maximal heart rate. There was no significant difference between mean
      heart rate and estimated HRR values (P=.70). CONCLUSIONS: In adults with impaired
      walking resulting from stroke, VT can be safely measured during submaximal
      treadmill walking. Participants were able to sustain walking at VT, and this
      value may provide an appropriate stimulus for aerobic exercise prescription in
      this population.

PMID- 25979163
TI  - QTL mapping of fungicide sensitivity reveals novel genes and pleiotropy with
      melanization in the pathogen Zymoseptoria tritici.
AB  - A major problem associated with the intensification of agriculture is the
      emergence of fungicide resistance. Azoles are ergosterol biosynthesis inhibitors
      that have been widely used in agriculture and medicine since the 1970s, leading
      to emergence of increasingly resistant fungal populations. The known genetic
      mechanisms underlying lower azole sensitivity include mutations affecting the
      CYP51 gene that encodes the target protein, but in many cases azole resistance is
      a more complex trait with an unknown genetic basis. We used quantitative trait
      locus (QTL) mapping to identify genes affecting azole sensitivity in two crosses
      of Zymoseptoria tritici, the most damaging wheat pathogen in Europe. Restriction
      site associated DNA sequencing (RADseq) was used to genotype 263 (cross 1) and
      261 (cross 2) progeny at ~ 8500 single nucleotide polymorphisms (SNP) and
      construct two dense linkage maps. Azole sensitivity was assessed using high
      throughput digital image analysis of colonies growing on Petri dishes with or
      without the fungicide propiconazole. We identified three QTLs for azole
      sensitivity, including two that contained novel fungicide sensitivity genes. One
      of these two QTLs contained only 16 candidate genes, among which four most likely
      candidates were identified. The third QTL contained ERG6, encoding another
      protein involved in ergosterol biosynthesis. Known genes in QTLs affecting colony
      growth included CYP51 and PKS1, a gene affecting melanization in Z. tritici. PKS1
      showed compelling evidence for pleiotropy, with a rare segregating allele that
      increased melanization while decreasing growth rate and propiconazole
      sensitivity. This study resolved the genetic architecture of an important
      agricultural trait and led to identification of novel genes that are likely to
      affect azole sensitivity in Z. tritici. It also provided insight into fitness
      costs associated with lowered azole sensitivity and suggests a novel fungicide
      mixture strategy.

PMID- 25979164
TI  - Editorial.

PMID- 25979165
TI  - An atypical acute small-bowel obstruction.

PMID- 25979166
TI  - Ultra-sensitive high performance liquid chromatography-laser-induced fluorescence
      based proteomics for clinical applications.
AB  - An ultra-sensitive high performance liquid chromatography-laser induced
      fluorescence (HPLC-LIF) based technique has been developed by our group at
      Manipal, for screening, early detection, and staging for various cancers, using
      protein profiling of clinical samples like, body fluids, cellular specimens, and
      biopsy-tissue. More than 300 protein profiles of different clinical samples
      (serum, saliva, cellular samples and tissue homogenates) from volunteers (normal,
      and different pre-malignant/malignant conditions) were recorded using this set
      up. The protein profiles were analyzed using principal component analysis (PCA)
      to achieve objective detection and classification of malignant, premalignant and
      healthy conditions with high sensitivity and specificity. The HPLC-LIF protein
      profiling combined with PCA, as a routine method for screening, diagnosis, and
      staging of cervical cancer and oral cancer, is discussed in this paper.
      BIOLOGICAL SIGNIFICANCE: In recent years, proteomics techniques have advanced
      tremendously in life sciences and medical sciences for the detection and
      identification of proteins in body fluids, tissue homogenates and cellular
      samples to understand biochemical mechanisms leading to different diseases. Some
      of the methods include techniques like high performance liquid chromatography, 2D
      gel electrophoresis, MALDI-TOF-MS, SELDI-TOF-MS, CE-MS and LC-MS techniques. We
      have developed an ultra-sensitive high performance liquid chromatography-laser
      induced fluorescence (HPLC-LIF) based technique, for screening, early detection,
      and staging for various cancers, using protein profiling of clinical samples
      like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein
      profiles of different clinical samples (serum, saliva, cellular samples and
      tissue homogenates) from healthy and volunteers with different malignant
      conditions were recorded by using this set-up. The protein profile data were
      analyzed using principal component analysis (PCA) for objective classification
      and detection of malignant, premalignant and healthy conditions. The method is
      extremely sensitive to detect proteins with limit of detection of the order of
      femto-moles. The HPLC-LIF combined with PCA as a potential proteomic method for
      the diagnosis of oral cancer and cervical cancer has been discussed in this
      paper. This article is part of a Special Issue entitled: Proteomics in India.

PMID- 25979167
TI  - Characterization, antioxidative and ACE inhibitory properties of hydrolysates
      obtained from thornback ray (Raja clavata) muscle.
AB  - Thornback ray muscle hydrolysates (TRMHs) prepared by treatment with proteases
      from Bacillus subtilis A26 (TRMH-A26), Raja clavata crude alkaline protease
      extract (TRMH-Crude), Alcalase (TRMH-Alcalase) and Neutrase (TRMH-Neutrase) were
      elaborated and their antioxidant properties and angiotensin I-converting enzyme
      (ACE) inhibitory activities were tested. TRMHs showed different degrees of
      hydrolysis (DH from 11 to 22%) and hydrophobic/hydrophilic peptide ratio. Protein
      content varied from 71 to 74%. Gly, Pro, Asp and Asn were the most prominent
      amino acids, while hypoxanthine was the major nucleotide related compound
      present. The antioxidant activity was assayed using various tests. TRMH-Neutrase
      exhibited the highest antioxidant activity in DPPH scavenging, reducing power and
      inhibition of beta-carotene bleaching tests. However in the total antioxidative
      efficacy, TRMH-Crude exhibited the highest activity. TRMH-Crude and TRMH-Neutrase
      were the most potent to prevent DNA oxidation by Fenton reagent. Concerning anti
      ACE activity, TRMH-A26 and TRMH-Neutrase exhibited the highest activity with 87%
      at 5mg/ml. The results revealed that TRMHs could be employed as a protein source
      in food additive processing or diets for aquatic organisms and other farmed
      animals. BIOLOGICAL SIGNIFICANCE: The present study explores for the first time
      the elaboration of enzymatic hydrolysates from thornback ray R. clavata. The
      hydrolysates are well characterized and showed an interesting protein content as
      well as the presence of nucleotide related compounds, essential amino acids and
      taurine, which make them an interesting source of fish meal in aquaculture feeds.
      The hydrolysates were found to exhibit ACE inhibitory activity and antioxidant
      activity. The hydrolysates could serve also as a potential protein source for
      functional foods.

PMID- 25979169
TI  - Integration of PKR-dependent translation inhibition with innate immunity is
      required for a coordinated anti-viral response.
AB  - Viral triggering of the innate immune response in infected cells aims at delaying
      viral replication and prevents tissue spreading. Viral replication is delayed by
      host protein synthesis inhibition and infected cell apoptosis on one hand, while
      infection spreading is controlled by the synthesis of specific proteins like type
      I interferons (IFNs) and pro-inflammatory cytokines on the other hand. How do
      these two apparent conflicting responses cooperate within the same infected cells
      to mount effective defenses against pathogens? What are the molecules or the
      complexes resolving this contradiction over time? Some recent studies reveal
      unanticipated connections between innate immunity and stress pathways, giving
      important clues on how the cellular responses are orchestrated to limit infection
      efficiently. 

PMID- 25979170
TI  - Changing channels in pain and epilepsy: Exploiting ion channel gene therapy for
      disorders of neuronal hyperexcitability.
AB  - Chronic pain and epilepsy together affect hundreds of millions of people
      worldwide. While traditional pharmacotherapy provides essential relief to the
      majority of patients, a large proportion remains resistant, and surgical
      intervention is only possible for a select few. As both disorders are
      characterised by neuronal hyperexcitability, manipulating the expression of the
      most direct modulators of excitability - ion channels - represents an attractive
      common treatment strategy. A number of viral gene therapy approaches have been
      explored to achieve this. These range from the up- or down-regulation of channels
      that control excitability endogenously, to the delivery of exogenous channels
      that permit manipulation of excitability via optical or chemical means. In this
      review we highlight the key experimental successes of each approach and discuss
      the challenges facing their clinical translation. 

PMID- 25979168
TI  - Small-molecule modulators of the constitutive androstane receptor.
AB  - INTRODUCTION: The constitutive androstane receptor (CAR) induces drug
      metabolizing enzymes for xenobiotic metabolism. AREAS COVERED: This review covers
      recent advances in elucidating the biological functions of CAR and its modulation
      by a growing number of agonists and inhibitors. EXPERT OPINION: Extrapolation of
      animal CAR function to that of humans should be carefully scrutinized,
      particularly when rodents are used in evaluating the metabolic profile and
      carcinogenic properties of clinical drugs and environmental chemicals. Continuous
      efforts are needed to discover novel CAR inhibitors, with extensive understanding
      of their inhibitory mechanism, species selectivity, and discriminating power
      against other xenobiotic sensors.

PMID- 25979171
TI  - HECT-type E3 ubiquitin ligases in nerve cell development and synapse physiology.
AB  - The development of neurons is precisely controlled. Nerve cells are born from
      progenitor cells, migrate to their future target sites, extend dendrites and an
      axon to form synapses, and thus establish neural networks. All these processes
      are governed by multiple intracellular signaling cascades, among which
      ubiquitylation has emerged as a potent regulatory principle that determines
      protein function and turnover. Dysfunctions of E3 ubiquitin ligases or aberrant
      ubiquitin signaling contribute to a variety of brain disorders like X-linked
      mental retardation, schizophrenia, autism or Parkinson's disease. In this review,
      we summarize recent findings about molecular pathways that involve E3 ligases of
      the Homologous to E6-AP C-terminus (HECT) family and that control neuritogenesis,
      neuronal polarity formation, and synaptic transmission. 

PMID- 25979172
TI  - Long non-coding RNA HOTAIR modulates c-KIT expression through sponging miR-193a
      in acute myeloid leukemia.
AB  - HOTAIR is significantly overexpressed in various cancers and facilitates tumor
      invasion and metastasis. However, whether HOTAIR plays oncogenic roles in acute
      myeloid leukemia (AML) is still unknown. Here, we report that HOTAIR expression
      was obviously increased in leukemic cell lines and primary AML blasts.
      Clinically, AML patients with higher HOTAIR predicted worse clinical outcome
      compared with those with lower HOTAIR. Importantly, HOTAIR knockdown by small
      hairpin RNA inhibited cell growth, induced apoptosis, and decreased number of
      colony formation. Finally, HOTAIR modulated c-KIT expression by competitively
      binding miR-193a. Collectively, our data suggest that HOTAIR plays an important
      oncogenic role in AML and might serve as a marker for AML prognosis and a
      potential target for therapeutic intervention. 

PMID- 25979173
TI  - The relevance of EMT in breast cancer metastasis: Correlation or causality?
AB  - Although major progress has been achieved in treating breast cancer patients,
      metastatic breast cancer still remains a deadly disease. A full understanding of
      the process of systemic cancer cell dissemination is therefore critical to
      develop next generation therapies. A plethora of experimental data points toward
      a central role of an epithelial to mesenchymal transition (EMT) in the multistep
      cascade of metastasis formation. However, in patients the data are based on
      correlative studies which often, but not always, tie the expression of EMT
      markers to cancer invasion, metastasis and poor clinical outcome. Moreover, the
      notion that cancer cells are able to switch between different modes of migration
      asks for a thorough review of the actual relevance of EMT in cancer metastasis. 

PMID- 25979174
TI  - G-quadruplexes: Emerging roles in neurodegenerative diseases and the non-coding
      transcriptome.
AB  - G-rich sequences in DNA and RNA have a propensity to fold into stable secondary
      structures termed G-quadruplexes. G-quadruplex forming sequences are widespread
      throughout the human genome, within both, protein coding and non-coding genes,
      and regulatory regions. G-quadruplexes have been implicated in multiple cellular
      functions including chromatin epigenetic regulation, DNA recombination,
      transcriptional regulation of gene promoters and enhancers, and translation. Here
      we will review the evidence for the occurrence of G-quadruplexes both in vitro
      and in vivo; their role in neurological diseases including G-quadruplex-forming
      repeat expansions in the C9orf72 gene in frontotemporal dementia and amyotrophic
      lateral sclerosis and loss of the G-quadruplex binding protein FMRP in the
      intellectual disability fragile X syndrome. We also review mounting evidence that
      supports a role for G-quadruplexes in regulating the processing or function of a
      range of non-coding RNAs. Finally we will highlight current perspectives for
      therapeutic interventions that target G-quadruplexes. 

PMID- 25979175
TI  - Identification and functional analysis of 2-hydroxyflavanone C
      glucosyltransferase in soybean (Glycine max).
AB  - C-Glucosyltransferase is an enzyme that mediates carbon-carbon bond formation to
      generate C-glucoside metabolites. Although it has been identified in several
      plant species, the catalytic amino acid residues required for C-glucosylation
      activity remain obscure. Here, we identified a 2-hydroxyflavanone C
      glucosyltransferase (UGT708D1) in soybean. We found that three residues, His20,
      Asp85, and Arg292, of UGT708D1 were located at the predicted active site and
      evolutionarily conserved. The substitution of Asp85 or Arg292 with alanine
      destroyed C-glucosyltransferase activity, whereas the substitution of His20 with
      alanine abolished C-glucosyltransferase activity but enabled O
      glucosyltransferase activity. The catalytic mechanism is discussed on the basis
      of the findings. 

PMID- 25979177
TI  - PI3K-C2alpha: One enzyme for two products coupling vesicle trafficking and signal
      transduction.
AB  - The spatial restriction of phosphorylated phosphoinositides generated downstream
      activated membrane receptors is critical for proper cell response to
      environmental cues. The alpha isoform of class II PI3Ks, PI3K-C2alpha, has
      emerged as a modulator of receptor localization, acting both in the control of
      receptor endocytosis and resensitization. This unexpectedly versatile enzyme was
      found to differentially produce two distinct 3-phosphorylated phosphoinositides
      and to selectively control distinct steps of vesicular traffic such as
      endocytosis and recycling. This review focuses on the latest discoveries
      regarding PI3K-C2alpha function in vesicle trafficking and its impact on cell
      biology and mammalian embryonic development. 

PMID- 25979178
TI  - Patient-reported outcomes to initiate a provider-patient dialog for the
      management of hip and knee osteoarthritis.
AB  - PURPOSE: Although many treatment guidelines exist for hip and knee osteoarthritis
      (OA), uptake in clinical practice is typically low. Valid patient-reported
      outcome measures (PROs) that can be easily used in the clinic could aid
      implementation and evaluation of treatment recommendations, and the tracking of
      symptoms and function over time. This project responded to a 2012 Call to Action
      of the Chronic Osteoarthritis Management Initiative of the United States Bone and
      Joint Initiative; we aimed to develop a tiered list of recommended PROs that
      could be feasibly applied in common clinical settings, across four domains of
      pain, function, fatigue, and sleep. METHODS: PROs were identified through a
      focused literature review. Clinicians and researchers with OA expertise evaluated
      each measure' feasibility for use in routine clinical practice, followed by
      meaningfulness in assessing OA outcomes. Eligible PROs were categorized by domain
      and ranked into Tiers One (very brief measures for initial use in clinical
      settings), Two (brief measures with more in-depth assessment), and Three (most
      detailed assessment). RESULTS: Total PROs identified were 172 for pain, 160 for
      function, 55 for fatigue, and 60 for sleep. Of these, 9 pain, 7 function, 7
      fatigue, and 8 sleep PROs were ranked into one of three tiers. CONCLUSIONS: This
      three-tiered list of recommended PROs provides a basis for tools to
      systematically track outcomes, facilitate provider-patient dialog, and guide
      treatment for hip or knee OA. Research is needed to test the utility and
      feasibility of systematic implementation of these measures in primary care and
      specialty clinical settings.

PMID- 25979176
TI  - Neuronal responses to stress and injury in C. elegans.
AB  - The nervous system plays critical roles in the stress response. Animals can
      survive and function under harsh conditions, and resist and recover from injuries
      because neurons perceive and respond to various stressors through specific
      regulatory mechanisms. Caenorhabditis elegans has served as an excellent model to
      discover fundamental mechanisms underlying the neuronal response to stress. The
      basic physiological processes that C. elegans exhibits under stress conditions
      are similar to those observed in higher organisms. Many molecular pathways
      activated by environmental and cellular stresses are also conserved. In this
      review, we summarize major findings in examining neuronal responses to hypoxia,
      oxidative stress, osmotic stress, and traumatic injury. These studies from C.
      elegans have provided novel insights into our understanding of neuronal responses
      to stress at the molecular, cellular, and circuit levels. 

PMID- 25979179
TI  - Answer to D. Palamar's letter to the editor: "Comment on 'Piriformis muscle
      syndrome: Diagnostic criteria and treatment of a monocentric series of 250
      patients' by F. Michel et al." Ann Phys Rehabil Med (2015)
      doi:10.1016/j.rehab.2015.01.005.

PMID- 25979180
TI  - Can a school-based sleep education programme improve sleep knowledge, hygiene and
      behaviours using a randomised controlled trial.
AB  - OBJECTIVES: The present study investigated the effectiveness of a school-based
      sleep education programme in improving key sleep behaviours, sleep knowledge, and
      sleep hygiene. DESIGN AND METHODS: A cross-sectional cluster-randomised
      controlled trial with two groups (Intervention and Control) and three assessment
      time points [baseline, immediately post intervention (6 weeks post baseline) and
      follow-up (18 weeks post baseline)] was employed. A total of 296 students (mean
      age = 12.2 +/- 0.6 years; 59% female) from 12 schools in Adelaide, South
      Australia, were recruited, with 149 participants in the Intervention group and
      147 in the Control group. The intervention consisted of four classroom lessons
      delivered at weekly intervals, followed by a group project on sleep topics, which
      students presented at a parental information evening. Sleep patterns were
      assessed objectively (actigraphy, n = 175) and subjectively (time-use recall, n =
      251) at three time points. Sleep knowledge and sleep hygiene (n = 296) were also
      measured. RESULTS: Generalised estimating equations were used to compare changes
      in the Intervention and Control groups. The programme increased time in bed by 10
      min (p = 0.03) for the Intervention group relative to the Control group, due to a
      10-min delay in wake time (p = 0.00). These changes were not sustained at follow
      up. There was no impact on sleep knowledge or sleep hygiene. CONCLUSION:
      Investment in the sleep health of youth through sleep education is important but
      changes to sleep patterns are difficult to achieve. More intensive programmes,
      programmes with a different focus or programmes targeting different age groups
      may be more effective.

PMID- 25979181
TI  - Restless legs syndrome: clinical presentation diagnosis and treatment.
AB  - Restless legs syndrome (RLS) is a circadian disorder of sensory-motor integration
      that may be related to genetically determined dysregulation of iron transport
      across the blood-brain barrier. Dopamine agonists (DAs) have been considered the
      first-line therapy, but with the growing appreciation of problems associated with
      long-term treatment, particularly augmentation and impulse control disorder,
      alpha-2-delta drugs, such as gabapentin, are now considered the first line of
      treatment in patients with troublesome RLS. Opioids can be considered as an
      alternative therapy, particularly in patients with DA-related augmentation. In
      more severe cases, a combination therapy may be required. Intravenous iron
      therapy may be considered on those patients with refractory RLS. 

PMID- 25979182
TI  - Publication analysis on insomnia: how much has been done in the past two decades?
AB  - Insomnia has been a rising public concern in recent years. As one example of a
      multidisciplinary topic, the theme of insomnia research has gradually shifted
      over time; however, there is very little quantitative characterization of the
      research trends in insomnia. The current study aims to quantitatively analyze
      trends in insomnia publications for the past 20 years. We retrospectively
      analyzed insomnia-related publications retrieved from PubMed and Google Scholar
      between 1994 and from a number of different perspectives. We investigated the
      major areas of research focus for insomnia, journal characteristics, as well as
      trends in clinical management and treatment modalities. The resulting 5841
      publications presented an exponential growth trend over the past two decades,
      with mean annual growth rates at nearly 10% for each publication type. Analysis
      of major research focuses indicated that depression, hypnotics and sedatives,
      questionnaires, and polysomnography are the most common topics at present.
      Furthermore, we found that while studies on drug therapy and adverse effects
      decreased in the most recent five years, the greatest expansion of insomnia
      publications were in the areas of cognitive behavioral therapy for insomnia (CBT
      I) and alternative therapies. Collectively, insomnia publications present a
      continuous trend of increase. While sedative and hypnotic drugs dominated the
      treatment of insomnia, non-pharmacological therapies may have great potential for
      advancement in future years. Future research effort is warranted for novel tools
      and clinical trials, especially on insomnia treatments with inadequate evidence
      or not-yet-clear efficacy and side effects. 

PMID- 25979183
TI  - Gait analysis to guide a selective dorsal rhizotomy program.
AB  - Selective dorsal rhizotomy is a valuable surgical option to manage spasticity in
      children with bilateral cerebral palsy with the objective of improving function.
      Choosing the correct patient for rhizotomy requires considerable effort and a
      comprehensive evaluation. Instrumented three-dimensional gait analysis provides
      supporting evidence in the selection of the ideal child for SDR as well as
      enabling quantitative monitoring of outcome and post-operative management up to
      skeletal maturity. 

PMID- 25979184
TI  - Endorsing and implementing reporting guidelines in journals.

PMID- 25979185
TI  - The role of nurses in HIV screening in health care facilities: A systematic
      review.
AB  - OBJECTIVE: To examine nurse-driven HIV screening in various health care settings
      in terms of its impact on test offering, acceptance and delivery rates, nursing
      responsibilities, staff perceptions and long-term implementation. DESIGN:
      Systematic review. REVIEW METHODS: The systematic review conducted in September
      2014 adheres to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement. Two independent reviewers extracted and summarised
      the eligible studies using a standardised form. STUDY ELIGIBILITY CRITERIA: All
      studies published from 2004 to 2014 that explored nurse-driven HIV screening
      practice in health care facilities in countries with comparable concentrated HIV
      epidemics were included. DATA SOURCES: MEDLINE, EBSCO CINAHL. RESULTS: Overall,
      30 quantitative, qualitative and mixed methods studies fulfilled the eligibility
      criteria. The studies showed a trend in higher test offering, better acceptance
      and higher delivery rates with the implementation of nurse-driven HIV screening.
      However, among the 23 studies (77%) that evaluated these aims, only 13 studies
      (56%) had a control group, and 4 studies (17%) were randomised controlled trials
      (RCT) in few centres (i.e., 1 or 2). In 2 studies that compared nurse-driven HIV
      test offering to physician intervention, the participation of nurses was higher
      than that of physicians (85% vs. 54%, p<0.001; 47% vs. 28%, p<0.05). In a third
      study, the intervention of a dedicated nurse increased the test offering from
      96.5% to 99.5% (OR=7.27, 95% CI=1.02-316.9). Acceptance rates increased with the
      nurse intervention in 2 RCTs (75% vs. 71%, p=0.025; 45% vs. 19%, p<0.05) and in a
      cohort study (74.8% vs. 84.3%, OR=1.82, 95% CI=1.14-2.88), whereas it decreased
      in 2 other studies. The testing rates increased in 7 out of 10 studies, with a
      maximum absolute increase of 65.9%. Nurse-driven HIV screening was evaluated at
      the time of routine HIV screening implementation in 27 studies (90%) and provided
      nurses with new responsibilities in 9 studies (30%). The few studies (23%) that
      explored how health care professionals, including nurses, perceived the strategy
      showed that this approach was well received. However, several operational
      barriers, such as lack of time, prevented its long-term implementation.
      CONCLUSION: The review supports the implementation of nurse-driven HIV screening.
      However, the evaluation of the impact of the nurse approach by RCTs was scarce,
      calling for additional research to better evaluate the impact of the nursing
      profession's contribution to HIV screening. Moreover, the perceptions of nurses
      and health care staff were seldom evaluated and require further exploration to
      improve nurse-driven HIV screening implementation.

PMID- 25979186
TI  - Differences in antiretroviral safety and efficacy by sex in a multinational
      randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Worldwide, 50% of human immunodeficiency virus (HIV)
      infected people are women. This study was to evaluate whether the safety and
      efficacy outcomes of three initial antiretroviral regimens (ARVs) differed by
      sex. METHODS: Antiretroviral regimen naive participants from nine countries in
      four continents were assigned to ARVs with efavirenz (EFV) plus lamivudine
      zidovudine, atazanavir (ATV) plus didanosine (ddI)-EC/emtricitabine (FTC) or EFV
      plus FTC-tenofovir-DF. The primary objective was to estimate the sex difference
      on efficacy outcome of treatment failure defined as one of the following: 1. Time
      to 1st of confirmed virologic failure, 2. WHO Stage 4 progression or 3. death
      with hazard ratio (HR) and 95% confidence interval (CI) from adjusted Cox
      regression models. RESULTS: In all, 739 (47%) women and 832 (53%) men with HIV
      were evaluated. Women had higher pretreatment CD4+(182 vs 165 cells/mm(3); P <
      0.001) and lower HIV-1 RNA (4.9 log10 vs 5.2 log10 copies/ml; P < 0.001) compared
      to men. Association of sex with time to regimen failure differed by treatment arm
      (P = 0.018). For atazanavir plus didanosine-EC plus emtricitabine, women had a
      longer time to treatment failure compared to men [adjusted HR (aHR) = 0.59; 95%
      CI 0.40-0.87]. Women were less likely to prematurely discontinue treatment
      prematurely (aHR = 0.74; 95% CI 0.56-0.98). Women assigned to efavirenz plus
      lamivudine-zidovudine were more likely to have a primary safety event compared to
      men (aHR = 1.49; 95% CI 1.18-1.88). CONCLUSION: Antiretroviral efficacy and
      safety differed by sex in this study. Consideration of potential effects of sex
      on antiretroviral outcomes is important for the design of future clinical trials
      and for HIV treatment guidelines.

PMID- 25979188
TI  - Treatment of Arthritis Associated With Legg-Calve-Perthes Disease With Modular
      Total Hip Arthroplasty.
AB  - Legg-Calve-Perthes (LCP) disease can result in morphological deformities and
      associated adult hip arthritis. Thirty-five consecutive total hip arthroplasties
      (THA) were performed in 28 patients with a history of LCP using a non-cemented
      modular femoral component. There was one revision for late hematogenous infection
      and no evidence of prosthesis failure. Harris hip scores, on average, improved
      from 49.8 (26-73) to 93.9 (82-100) (P<0.05) after a minimum of 2 years follow-up
      (average, 8.2 years, range 2-14 years). Clinically, patients demonstrated
      diminished or no limping (94%, 33/35) and improved leg length equality post
      operatively (100%, 35/35). This style of stem accommodated metaphyseal/diaphyseal
      size mismatch in 80% (28/35), allowed for abnormal anteversion in 71% (25/35),
      and resulted in radiographic improvements in trochanteric height (P<0.05), body
      weight lever arm (P<0.05), and leg length (P<0.05).

PMID- 25979187
TI  - A descriptive study of the characteristics of differentiated thyroid cancer in
      Catalonia during the period 1998-2012. The CECaT registry.
AB  - INTRODUCTION: The consortium for the study of thyroid cancer (CECaT), including
      20 hospitals and one research institute, was recently created in Catalonia
      (Spain). One of the first initiatives of the group was to perform a descriptive
      analysis of the characteristics of patients with differentiated thyroid carcinoma
      (DTC). PATIENTS AND METHODS: The cohort included 1,855 patients from 11 hospitals
      treated over a period of 15 years (1998-2012). RESULTS: In this series, 1.470
      (79.2%) patients were women. Mean age was 47.7 (15.7) years old. Age was
      significantly higher in male than in female patients, 49.3 (15) versus 47.3
      (15.8); p=0.02. Papillary thyroid carcinoma accounted for 88.9% of cases. Mean
      tumor size was 21.5 (16) mm, and was significantly lower in females than in
      males, 20.1 (14.5) mm and 26.6 (20.3) mm respectively (p<0.001). After a follow
      up period of 5.5 (3.7) years, information was available for 1,355 patient, of
      whom 1065 (78.6%) were free of disease, 239 (17.6%) had no tumor persistence, and
      51 (3.8) % had died. The risk of persistent or recurrent disease was
      significantly associated to older age at diagnosis, male gender, larger tumor
      size, lymph node metastases at surgery, no signs of thyroiditis in the remaining
      thyroid tissue, and presence of vascular and/or extraglandular invasion.
      CONCLUSIONS: Patient characteristics analyzed are similar to those reported in
      other parts of the world.

PMID- 25979189
TI  - Readmission Rates in Total Hip Arthroplasty: A Granular Analysis?
AB  - A deeper understanding of readmissions in arthroplasty is warranted. We wanted to
      determine in primary THA patients: readmission rates; baseline characteristics of
      patients with/without readmissions; and readmission reasons. 201 consecutive
      patients were studied. Preoperative characteristics, patient-perceived-outcomes,
      and hip-scores were compared between patients with and without readmissions.
      Rates were 1% (readmitted n=2; 15-days), 3.5% (7; 30-days), 6.5% (13; 90-days),
      and 16.9% (34; 1-year). Readmitted patients had significantly worse preoperative
      comorbidities/outcome-scores when compared to non-readmitted patients. "Surgical
      site infection" was the most frequent readmission reason within 30/90days. Within
      1year, it was another elective joint. Fifty percent of readmissions were not
      related to the index-surgery (15-days). Preoperative health status affects rates.
      Many rehospitalizations are not related to the index-surgery and probably
      unpreventable. 

PMID- 25979191
TI  - The effect of conventional surgery and piezoelectric surgery bone harvesting
      techniques on the donor site morbidity of the mandibular ramus and symphysis.
AB  - The aim of this study was to evaluate the morbidity following bone harvesting at
      two different intraoral donor sites, mandibular symphysis and ramus, and to
      determine the effects of piezoelectric and conventional surgical graft harvesting
      techniques on donor site morbidity. Intraoral block bone grafts were harvested
      from the symphysis (n=44) and ramus (n=31). The two donor site groups were
      divided into two subgroups according to the surgical graft harvesting method used
      (conventional or piezoelectric surgery). Intraoperative and postoperative pain
      was assessed using a visual analogue scale (VAS). Donor site morbidity and the
      harvesting techniques were compared statistically. Of 290 teeth evaluated in the
      symphysis group, four needed root canal treatment after surgery. The incidence of
      transient paresthesia in the mucosa was significantly higher in the symphysis
      group than in the ramus group (P=0.004). In the symphysis group, the incidence of
      temporary skin and mucosa paresthesia was lower in the piezoelectric surgery
      subgroup than in the conventional surgery subgroup (P=0.006 and P=0.001,
      respectively). No permanent anaesthesia of any region of the skin was reported in
      either donor site group. VAS scores did not differ between the ramus and
      symphysis harvesting groups, or between the piezoelectric and conventional
      surgery subgroups. When the symphysis was chosen as the donor site, minor sensory
      disturbances of the mucosa and teeth were recorded. The use of piezoelectric
      surgery during intraoral harvesting of bone blocks, especially from the
      symphysis, can reduce these complications. 

PMID- 25979190
TI  - Evaluation of the effect of low-level diode laser therapy applied during the bone
      consolidation period following mandibular distraction osteogenesis in the human.
AB  - The aim of this study was to evaluate the effect of low-level laser therapy
      (LLLT) on new bone formation obtained by distraction osteogenesis in the early
      consolidation period. Ten selected patients with bilateral mandibular retrusion
      seen at the Nasser Institute Hospital, Egypt between June 2009 and June 2012
      underwent this clinical trial; seven were female and three were male, and their
      mean age was 31+/-5.1 years. The left mandible of each patient was assigned to
      group A (n=10) and the right mandible to group B (n=10); mandibular distraction
      osteogenesis was performed on both sides and then LLLT was used in group B only.
      The amounts of bone acquired were compared according to their radiographic
      density on digital panoramic radiographs after 6, 12, 24, and 54 days of
      consolidation. Statistically significant differences in bone density were found
      between the two groups. Group B showed bone consolidation and growth differences
      on day 6 (P=0.402), day 12 (P=0.006), day 24 (P=0.021), and day 54 (P=0.028). The
      use of LLLT on distracted bone was found to increase the quality and quantity of
      bone and to shorten the consolidation period, allowing early removal of the
      distractor and resulting in decreased morbidity and relapse. 

PMID- 25979192
TI  - Daily left prefrontal repetitive transcranial magnetic stimulation for medication
      resistant burning mouth syndrome.
AB  - Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the
      mouth in the absence of any abnormal organic findings. The pathophysiology of BMS
      is unclear and its treatment is not fully established. Although antidepressant
      medication is commonly used for treatment, there are some medication-resistant
      patients, and a new treatment for medication-resistant BMS is needed. Repetitive
      transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation
      technology approved by the US Food and Drug Administration (FDA) for the
      treatment of depression. Recent studies have found beneficial effects of TMS for
      the treatment of pain. A case of BMS treated successfully with daily left
      prefrontal rTMS over a 2-week period is reported here. Based on this patient's
      clinical course and a recent pain study, the mechanism by which TMS may act to
      decrease the burning pain is discussed. 

PMID- 25979193
TI  - Efficacy of radiofrequency ablation for initial recurrent hepatocellular
      carcinoma after curative treatment: Comparison with primary cases.
AB  - OBJECTIVE: To determine the efficacy of radiofrequency ablation (RFA) for initial
      recurrence of small hepatocellular carcinoma (HCC; <=3 nodules, each nodule <=3cm
      in diameter) after curative treatment and identify prognostic factors affecting
      therapeutic outcome, we compared clinical and outcome factors between patients
      with primary HCC and those with initial recurrent HCC who underwent RFA. METHODS:
      In this retrospective cohort study, 211 HCC patients who underwent RFA were
      enrolled and comprised two groups: primary group (n=139) and initial recurrent
      group (n=72). We compared local tumor progression, overall survival (OS), disease
      free survival (DFS), and RFA safety between the groups. RESULTS: Median follow-up
      was 53 months. Local tumor progression rate was 5.8% in the primary group and
      4.2% in the recurrent group. OS rates at 5 years and 10 years were 63.2% and
      25.5% in the primary group and 54.5% and 33.4% in the recurrent group,
      respectively. Corresponding DFS rates were 30.7% and 14.6% and 19.2% and 11.0%.
      DFS was significantly shorter in the recurrent group (hazard ratio [HR]=1.81; 95%
      confidence interval [CI], 1.27-2.57; P=0.001). In the recurrent group, time from
      primary HCC development to recurrence was a determinant of OS (<=2 years;
      HR=3.42; 95% CI, 1.52-7.72; P=0.003). CONCLUSION: Although local tumor control
      and OS were similar between the groups, the recurrent group had shorter DFS than
      the primary group. Time from primary HCC development to recurrence was a
      prognostic factor for recurrence of HCC.

PMID- 25979194
TI  - Protein-protein interaction network analysis and identifying regulation microRNAs
      in asthmatic children.
AB  - BACKGROUND: Asthma is a chronic inflammatory airway disease, the incidence of
      which has increased recently. In order to identify the potential biomarkers for
      allergic asthma therapy, microarray data were analysed to find meaningful
      information. METHODS: Microarray data GSE18965 were downloaded from Gene
      Expression Ominibus (GEO), including seven asthmatic epithelium samples from
      children with allergic asthma and nine healthy controls. Limma package was used
      to detect differentially expressed genes (DEGs) and the criteria were |log fold
      change|>0.5 and p value<0.05. We used Database for Annotation, Visualization and
      Integrated Discovery (DAVID) tool to perform GO function and KEGG pathway
      analysis. STRING database was used to construct protein-protein interaction (PPI)
      network. MicroRNA (miRNA) regulation network was constructed according to
      miRecords database. RESULTS: We identified 274 DEGs in asthma epithelium samples
      comparing with healthy controls. There were 123 up-regulated DEGs and 151 down
      regulated DEGs. PPI network analysis showed that TSPO, G6PD and TXN had higher
      degree. miRNA regulation network demonstrated that miR-16 and miR-15a had higher
      degree. The target genes of miRNAs were significantly enriched in the apoptosis
      function. CONCLUSIONS: TSPO, G6PD and TXN, miR-16, miR-15a and apoptosis may be
      used as the targets for children's allergic asthma therapy.

PMID- 25979195
TI  - Identification of therapeutic targets for childhood severe asthmatics with DNA
      microarray.
AB  - BACKGROUND: In this study, we aimed to discover potential gene targets for
      treating childhood asthmatics. METHODS: With the microarray data downloaded from
      Gene Expression Omnibus (GEO) database, we explored the common differentially
      expressed genes (DEGs) in children with severe asthma and mild asthma (SA vs. MA)
      or healthy controls (SA vs. HC). Then we performed hierarchical clustering,
      function and pathway enrichment analysis for the common DEGs. RESULTS: A total of
      81 genes were identified to be differentially expressed in SA vs. MA and SA vs.
      HC group. Hierarchical clustering of the 81 DEGs could crudely separate the SA,
      MA and healthy individuals. The overrepresented GO terms of the common DEGs were
      related with lipid biosynthetic process (21.74%), pigment biosynthetic process
      (13.04%) and nucleoside monophosphate metabolic process (13.04%). Only one
      pathway was significantly enriched, which was the antigen processing and
      presentation pathway involved with CD4 and RFX gene. CONCLUSIONS: The antigen
      processing and presentation pathway and lipid biosynthetic process may play roles
      in the pathogenesis of severe asthma. CD4 and RFX provide a therapeutic
      possibility for childhood asthma.

PMID- 25979197
TI  - A comparison of the efficacy of 70% v/v isopropyl alcohol with either 0.5% w/v or
      2% w/v chlorhexidine gluconate for skin preparation before harvest of the long
      saphenous vein used in coronary artery bypass grafting.
AB  - BACKGROUND: Chlorhexidine gluconate (CHG) is often recommended for skin
      antisepsis; however, the most efficacious concentration is currently unclear. Our
      objective was to compare the efficacy of 70% isopropyl alcohol (IPA) containing
      either 0.5% or 2% CHG for antiseptic skin preparation in patients undergoing
      coronary artery bypass grafting. METHODS: One hundred patients were randomized to
      1 of the 2 CHG concentrations. The designated antiseptic was applied to the skin
      of the operative site of patients before long saphenous vein harvest. Bacterial
      counts on the skin incision site were determined at various time points to assess
      any immediate and persistent antimicrobial activity. The number of patients
      developing surgical site infection was also determined. RESULTS: The total
      numbers of microorganisms on the skin 2 minutes after skin antisepsis and after
      wound closure was lower with 2% CHG/70% IPA compared with 0.5% CHG/70% IPA (P =
      .033 and P = .016, respectively). Six of 41 patients in the 0.5% CHG/70%IPA group
      developed a superficial surgical site infection compared with 2 of 44 patients in
      the 2% CHG/70% IPA group (relative risk, 3.22; 95% confidence interval, 0.63
      22.75; P = .147). CONCLUSIONS: Isopropyl alcohol (70%) containing 2% CHG compared
      with 0.5% CHG reduces the number of microorganisms detectable on a surgical
      patient's skin perioperatively.

PMID- 25979198
TI  - Frenulectomy of the tongue and the influence of rehabilitation exercises on the
      sEMG activity of masticatory muscles.
AB  - This study aimed to assess by surface electromyography (sEMG) the changes in sub
      mental, orbicularis oris, and masticatory muscle activity after a lingual
      frenulectomy. Rehabilitation exercises in subjects with ankyloglossia,
      characterized by Class I malocclusion, were assessed as well. A total of 24
      subjects were selected. Thirteen subjects (mean age 7+/-2.5years) with Class I
      malocclusion and ankyloglossia were treated with lingual frenulectomy and
      rehabilitation exercises, while 11 subjects (mean age 7+/-0.8years) with normal
      occlusion and normal lingual frenulum were used as controls. The inclusion
      criteria for both groups were the presence of mixed dentition and no previous
      orthodontic treatment. The sEMG recordings were taken at the time of the first
      visit (T0), and after 1 (T1) and 6months (T2) for the treated group. Recordings
      were taken at the same time for the control group. Due to the noise inherent with
      the sEMG recording, special attention was paid to obtain reproducible and
      standardized recordings. The tested muscles were the masseter, anterior
      temporalis, upper and lower orbicularis oris, and sub-mental muscles. The sEMG
      recordings were performed at rest, while kissing, swallowing, opening the mouth,
      clenching the teeth and during protrusion of the mandible. These recordings were
      made by placing electrodes in the area of muscle contraction. At T0, the treated
      group showed different sEMG activity of the muscles with respect to the control
      group, with significant differences at rest and during some test tasks (p<0.05).
      In the treated group, an increase in sEMG potentials was observed for the
      masseter muscle, from T0 to T2, during maximal voluntary clenching. During
      swallowing and kissing, the masseter and sub-mental muscles showed a significant
      increase in their sEMG potentials from T0 to T2. During the protrusion of the
      mandible, the masseter and anterior temporalis significantly decreased their sEMG
      activity, while the sub-mental area increased significantly. No significant
      change was observed in the control group during the follow-up. The sEMG
      potentials of treated patients at T2 reached about the same values as those of
      the control group at T2. At T0 and T1 the differences between the two groups were
      more diffused, suggesting a clinical improvement of muscular functions after
      treatment. Lingual frenulectomy and rehabilitation exercises seem to affect the
      function of the orofacial muscles. Improvement in muscle sEMG potentials after
      treatment was demonstrated by sEMG, which can be considered the correct method to
      monitor this intervention. 

PMID- 25979196
TI  - Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related
      Mortality: Interrelationships Between Genetics and Acute Systemic and Central
      Nervous System BDNF Profiles.
AB  - BACKGROUND: Older adults have higher mortality rates after severe traumatic brain
      injury (TBI) compared to younger adults. Brain-derived neurotrophic factor (BDNF)
      signaling is altered in aging and is important to TBI given its role in neuronal
      survival/plasticity and autonomic function. Following experimental TBI, acute
      BDNF administration has not been efficacious. Clinically, genetic variation in
      BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) can
      be protective against acute mortality. Postacutely, these genotypes carry lower
      mortality risk in older adults and greater mortality risk among younger adults.
      OBJECTIVE: Investigate BDNF levels in mortality/outcome following severe TBI in
      the context of age and genetic risk. METHODS: Cerebrospinal fluid (CSF) and serum
      BDNF were assessed prospectively during the first week following severe TBI (n =
      203) and in controls (n = 10). Age, BDNF genotype, and BDNF levels were assessed
      as mortality/outcome predictors. RESULTS: CSF BDNF levels tended to be higher
      post-TBI (P = .061) versus controls and were associated with time until death (P
      = .042). In contrast, serum BDNF levels were reduced post-TBI versus controls (P
      < .0001). Both gene * BDNF serum and gene * age interactions were mortality
      predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to
      be negatively correlated post-TBI (P = .07). CONCLUSIONS: BDNF levels predicted
      mortality, in addition to gene * age interactions, suggesting levels capture
      additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to
      injury and age-related increases in pro-apoptotic BDNF target receptors. Negative
      CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit
      alterations. Understanding BDNF signaling in neuronal survival, plasticity, and
      autonomic function may inform treatment.

PMID- 25979199
TI  - Neurosurgical management of brain metastases.

PMID- 25979200
TI  - Continuum of care for persons with common mental health disorders in Nunavik: a
      descriptive study.
AB  - BACKGROUND: Changing Directions, Changing Lives, the Mental Health Strategy for
      Canada, prioritizes the development of coordinated continuums of care in mental
      health that will bridge the gap in services for Inuit populations. OBJECTIVE: In
      order to target ways of improving the services provided in these contexts to
      individuals in Nunavik with depression or anxiety disorders, this research
      examines delays and disruptions in the continuum of care and clinical, individual
      and organizational characteristics possibly associated with their occurrences.
      DESIGN: A total of 155 episodes of care involving a common mental disorder (CMD),
      incident or recurring, were documented using the clinical records of 79 frontline
      health and social services (FHSSs) users, aged 14 years and older, living in a
      community in Nunavik. Each episode of care was divided into 7 stages: (a)
      detection; (b) assessment; (c) intervention; (d) planning the first follow-up
      visit; (e) implementation of the first follow-up visit; (f) planning a second
      follow-up visit; (g) implementation of the second follow-up visit. Sequential
      analysis of these stages established delays for each one and helped identify when
      breaks occurred in the continuum of care. Logistic and linear regression analysis
      determined whether clinical, individual or organizational characteristics
      influenced the breaks and delays. RESULTS: More than half (62%) the episodes of
      care were interrupted before the second follow-up. These breaks mostly occurred
      when planning and completing the first follow-up visit. Episodes of care were
      more likely to end early when they involved anxiety disorders or symptoms,
      limited FHSS teams and individuals over 21 years of age. The median delay for the
      first follow-up visit (30 days) exceeded guideline recommendations significantly
      (1-2 weeks). CONCLUSION: Clinical primary care approaches for CMDs in Nunavik are
      currently more reactive than preventive. This suggests that recovery services for
      those affected are suboptimal.

PMID- 25979201
TI  - Intraganglionic interactions between satellite cells and adult sensory neurons.
AB  - Perineuronal satellite cells have an intimate anatomical relationship with
      sensory neurons that suggests close functional collaboration and mutual support.
      We examined several facets of this relationship in adult sensory dorsal root
      ganglia (DRG). Collaboration included the support of process outgrowth by
      clustering of satellite cells, induction of distal branching behavior by soma
      signaling, the capacity of satellite cells to respond to distal axon injury of
      its neighboring neurons, and evidence of direct neuron-satellite cell exchange.
      In vitro, closely adherent coharvested satellite cells routinely clustered around
      new outgrowing processes and groups of satellite cells attracted neurite
      processes. Similar clustering was encountered in the pseudounipolar processes of
      intact sensory neurons within intact DRG in vivo. While short term exposure of
      distal growth cones of unselected adult sensory neurons to transient gradients of
      a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma
      induced early and substantial growth of their distant neurites and branches, an
      example of local soma signaling. In turn, satellite cells sensed when distal
      neuronal axons were injured by enlarging and proliferating. We also observed that
      satellite cells were capable of internalizing and expressing a neuron
      fluorochrome label, diamidino yellow, applied remotely to distal injured axons of
      the neuron and retrogradely transported to dorsal root ganglia sensory neurons.
      The findings illustrate a robust interaction between intranganglionic neurons and
      glial cells that involve two way signals, features that may be critical for both
      regenerative responses and ongoing maintenance. 

PMID- 25979202
TI  - Evidence for viral infection as a causative factor of human biliary atresia.
AB  - OBJECTIVES: To explore the evidence for viral infections triggering human biliary
      atresia (BA) by reviewing archival original articles that analyzed human samples
      via polymerase chain reaction (PCR) experiments, considering the recent
      experimental trend of extensive use of rotaviral BA animal models. METHODS: A
      PubMed search retrieved original articles that reported the results of PCR
      experiments for detecting viral DNA or RNA in patient samples as proof of past
      infection. Search terms included the often-debated DNA or RNA viruses and BA.
      Special focus was directed toward PCR analyses that targeted reovirus and
      rotavirus, where PCR accuracy, specimen characteristics and their interpretations
      were compared. RESULTS: Nineteen studies were conducted on 16 different kinds of
      viruses using PCR, with 5 studies on reovirus, 3 on rotavirus, 10 on
      cytomegalovirus, 5 on Epstein-Barr virus, 4 on parvovirus B19, and so on. Among
      the papers suggesting a possible viral link to only BA, there was no study on
      reovirus, 1 on rotavirus, 3 on cytomegalovirus, 1 on EB virus, and 1 on
      papillomavirus. Of the 6 PCR studies on Reoviridae, 3 on reovirus and 2 on
      rotavirus were evaluated rigorously for experimental accuracy, including their
      sensitivity. Two research groups analyzed preoperative stool samples in addition
      to generic hepatobiliary tissue obtained at surgery. Sample collection timing
      varied widely, with storage period prior to PCR experimentation not revealed in
      most reports on Reoviridae. CONCLUSION: Although a considerable number of PCR
      studies have sought to clarify a viral role in the pathogenesis of BA using human
      samples, the findings have been contradictory and have not succeeded in achieving
      an obvious differentiation between causative and accidental infection of the
      focused virus. Reproducible and convincing evidence for a causative Reoviridae
      infection has been lacking based on objective data from highly sensitive PCR
      experiments. Even though the possibility remains of viral disappearance at the
      timing of collection, to avoid further ambiguous interpretations of PCR results,
      rigorous and meticulous collection of large numbers of specimens at carefully
      planned timing, along with a strictly adjusted and finely tuned PCR system, is
      strongly recommended for obtaining more reliable and consistent results.

PMID- 25979203
TI  - Investigating Factors that Bias the Reporting of Depression Symptomatology Among
      Older Australian Adults.
AB  - OBJECTIVE: To investigate factors that may bias the reporting of major depression
      symptoms among older adults, specifically the presence of physical conditions,
      bereavement, episode onset, and episode length. METHODS: A secondary data
      analysis of a nationally representative cross-sectional survey of community
      dwelling older Australian adults aged 50-85 years who completed the depression
      module in the 2007 Australian National Survey of Mental Health and Wellbeing
      (N=629) was conducted. Depression symptomatology was assessed according to
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria
      using the World Mental Health Composite International Diagnostic Interview.
      RESULTS: Multiple indicators multiple causes modeling indicated a unidimensional
      factor structure of depression. Two depressive symptoms displayed measurement
      noninvariance (i.e., nonequivalency): worthlessness/guilt and
      suicidality/thoughts of death. Specifically, older adults who were bereaved were
      significantly less likely to report worthlessness/guilt (OR: 0.29; 95% CI: 0.16
      0.50) and more likely to report suicidality/thoughts of death (OR: 4.67; 95% CI:
      2.84-7.68), compared with older adults who were not bereaved. Examination of
      latent mean differences revealed that older adults with physical conditions
      displayed significantly greater depression severity compared with older adults
      without physical conditions. CONCLUSION: The presence of physical conditions and
      episode onset and length do not appear to differentially influence reporting of
      depression symptoms among older Australian adults, suggesting these factors do
      not bias prevalence estimates of depression. Reporting of worthlessness/guilt and
      suicidality/thoughts of death may be biased toward older adults who are bereaved;
      however, these did not influence overall depression severity.

PMID- 25979204
TI  - What is the impact of sleeve gastrectomy and gastric bypass on metabolic control
      of diabetes? A clinic-based cohort of Mediterranean diabetic patients.
AB  - BACKGROUND: Effectiveness of sleeve gastrectomy and gastric bypass on glycemic,
      blood pressure, and lipids control in obese type 2 diabetic patients is poorly
      known. OBJECTIVE: To assess the effectiveness of bariatric surgery on obese
      patients with type 2 diabetes. SETTING: University hospital, Italy. METHODS:
      Diabetes remission and metabolic changes over postoperative follow-up were
      assessed in 135 obese patients with type 2 diabetes who underwent bariatric
      surgery in 2007-2011 (gastric bypass, n = 100; sleeve gastrectomy, n = 35).
      Repeated-measures analysis of variance and logistic regression were used.
      RESULTS: Diabetes remission was observed in 22% and 21.5% of the patients,
      respectively, 1 and 2 years after surgery. Compared with the remaining patients,
      patients in diabetes remission were significantly younger, had lower diabetes
      duration, hemoglobin A1c (HbA1c), fasting plasma glucose, and frequency of
      insulin treatment. Trends of HbA1c, body mass index (BMI), blood pressure, and
      plasma triglycerides revealed a significant decrease over time and the trend of
      HDL-cholesterol revealed a significant increase over time in both treatment
      groups (P<.001). Patients reaching target levels for at least 3 out of 5
      indicators of intermediate outcomes of care (composite indicator of good diabetes
      control) were 25.5% at the baseline and 66.1% at final follow-up visit (P<.001).
      In logistic regression, age (OR = .89, 95% CI .84-.95), HbA1c (OR = .67, 95% CI
      .49-0.91) and diabetes duration (OR = .87, 95% CI .77-1.00) were independent
      predictors of diabetes remission. CONCLUSIONS: Bariatric surgery is an effective
      approach to optimize glucose, lipids, and blood pressure control in obese type 2
      diabetic patients. Bariatric surgery should be offered earlier over the natural
      course of diabetes to increase the likelihood of diabetes remission in obese
      patients.

PMID- 25979205
TI  - Comparison between circular- and linear-stapled gastrojejunostomy in laparoscopic
      Roux-en-Y gastric bypass--a cohort from the Scandinavian Obesity Registry.
AB  - BACKGROUND: Although laparoscopic Roux-en-Y gastric bypass (LRYGB) is a common
      bariatric procedure worldwide, no consensus on the optimal technique for the
      gastrojejunostomy (GJ) has been reached. Circular stapling (CS) immediately
      results in a GJ of standardized width, whereas linear stapling (LS) requires a
      technically challenging closure of the stapler defect. The aim was to study
      differences in outcomes between CS and LS. SETTING: Nationwide Swedish cohort.
      METHODS: The Scandinavian Obesity Registry (SOReg) included prospective data from
      34,284 primary LRYGB patients operated on in 2007-2013. We studied operative
      time, length of hospital stay, postoperative complications, and percent excess
      body mass index loss (%EBMIL) after 1 year. Outcomes were assessed through
      multivariate analysis adjusting for gender, age, preoperative body mass index
      (BMI), and diabetes. RESULTS: Preoperatively the groups were similar (40.9 yr,
      BMI 42.4 kg/m(2), 76% female). For CS and LS, operative time and hospital stay
      were 114 and 73 minutes (P<.001) and 4.6 and 2.0 days (P<.001), respectively.
      Using LS as a reference, adjusted odds ratio (OR) for CS patients to have
      anastomotic leakage was 2.8 (95% CI 1.5-5.0), postoperative hemorrhage 1.9 (95%
      CI 1.2-2.9), wound complication 9.7 (95% CI 6.8-13.9), and marginal ulcer 3.1
      (95% CI 1.8-5.3). The %EBMIL at 1 year was 80% for both techniques and 31% of
      total weight was lost. Follow-up rate at 6 weeks and 1 year was 96% and 73%,
      respectively. CONCLUSION: CS was found to be associated with disadvantages
      regarding operative time, hospital stay, and postoperative complications compared
      with LS.

PMID- 25979206
TI  - Effects of omega-loop bypass on esophagogastric junction function.
AB  - BACKGROUND: At present, no objective data are available on the effect of omega
      loop gastric bypass (OGB) on gastroesophageal junction and reflux. OBJECTIVES: To
      evaluate the possible effects of OGB on esophageal motor function and a possible
      increase in gastroesophageal reflux. SETTING: University Hospital, Italy; Public
      Hospital, Italy. METHODS: Patients underwent clinical assessment for reflux
      symptoms, and endoscopy plus high-resolution impedance manometry (HRiM) and 24
      hour pH-impedance monitoring (MII-pH) before and 1 year after OGB. A group of
      obese patients who underwent sleeve gastrectomy (SG) were included as the control
      population. RESULTS: Fifteen OGB patients were included in the study. After
      surgery, none of the patients reported de novo heartburn or regurgitation. At
      endoscopic follow-up 1 year after surgery, esophagitis was absent in all patients
      and no biliary gastritis or presence of bile was recorded. Manometric features
      and patterns did not vary significantly after surgery, whereas intragastric
      pressures (IGP) and gastroesophageal pressure gradient (GEPG) statistically
      diminished (from a median of 15 to 9.5, P<.01, and from 10.3 to 6.4, P<.01,
      respectively) after OGB. In contrast, SG induced a significant elevation in both
      parameters (from a median of 14.8 to 18.8, P<.01, and from 10.1 to 13.1, P<.01,
      respectively). A dramatic decrease in the number of reflux events (from a median
      of 41 to 7; P<.01) was observed after OGB, whereas in patients who underwent SG a
      significant increase in esophageal acid exposure and number of reflux episodes
      (from a median of 33 to 53; P<.01) was noted. CONCLUSIONS: In contrast to SG, OGB
      did not compromise the gastroesophageal junction function and did not increase
      gastroesophageal reflux, which was explained by the lack of increased IGP and in
      GEPG as assessed by HRiM.

PMID- 25979207
TI  - Country of origin and bariatric surgery in Sweden during 2001-2010.
AB  - BACKGROUND: The prevalence of obesity, as well as use of bariatric surgery, has
      increased worldwide. The aim of the present study was to investigate the
      potential differences in the use of bariatric surgery among Swedes and immigrants
      in Sweden and whether the hypothesized differences remain after adjustment for
      socioeconomic factors. METHODS: A closed cohort of all individuals aged 20-64
      years was followed during 2001-2010. Further analyses were performed in 2 periods
      separately (2001-2005 and 2006-2010). Age-standardized cumulative incidence rates
      (CR) of bariatric surgery were compared between Swedes and immigrants considering
      individual variables. Cox proportional hazards models were used in univariate and
      multivariate models for males and females. RESULTS: A total of 12,791 Swedes and
      2060 immigrants underwent bariatric surgery. The lowest rates of bariatric
      surgery were found in immigrant men. The largest difference in CR between Swedes
      and immigrants was observed among low-income individuals (3.4 and 2.3 per 1000
      individuals, respectively). Adjusted hazard ratios (HRs) were lower for all
      immigrants compared with Swedes in the second period. The highest HRs were
      observed among immigrants from Chile and Lebanon and the lowest among immigrants
      from Bosnia. Except for Nordic countries, immigrants from all other European
      countries had a lower HR compared with Swedes. CONCLUSIONS: Men in general and
      some immigrant groups had a lower HR of bariatric surgery. Moreover, the
      difference between Swedes and immigrants was more pronounced in individuals with
      low socioeconomic status (income). It is unclear if underlying barriers to
      receive bariatric surgery are due to patients' preferences/lack of knowledge or
      healthcare structures. Future studies are needed to examine potential causes
      behind these differences.

PMID- 25979208
TI  - Is reimplantation of the duodenal-jejunal bypass liner feasible?
AB  - BACKGROUND: The endoscopic ally implanted DJBL is a 60-cm impermeable
      fluoropolymer device, which prevents food from making contact with the proximal
      intestine. It was designed to induce weight loss and treat type 2 diabetes
      mellitus (T2DM). OBJECTIVES: To evaluate the feasibility, safety, and
      effectiveness of duodenal-jejunal bypass liner (DJBL) reimplantation. SETTING:
      Prospective, observational study was conducted at the department of surgery and
      gastroenterology of the Rijnstate hospital, Arnhem, the Netherlands, between 2009
      and 2011. METHODS: Five obese patients with T2DM with body mass index (BMI) =
      Mass (kg) / height (m(2)), ranging from 30-35 kg/m(2) who completed the follow-up
      after their first implant and underwent removal of the DJBL after 6 months, were
      selected for reimplantation after an additional 18 months of follow-up. Weight
      loss, BMI, and HbA1 c were analyzed before and twelve months after
      reimplantation. RESULTS: In all 5 patients, the DJBL was implanted and explanted
      without any complications. Also the reimplantation and reexplantation occurred
      without any complications. Median weight decreased significantly from 105 kg to
      95 kg, and BMI decreased from 33 to 29. The glycated hemoglobin (HbA1 c) level
      decreased from 8.4% to 7.3% by the first implantation but it wasn't significant.
      CONCLUSIONS: Reimplantation of DJBL is feasible, deemed safe, and showed
      additional weight loss.

PMID- 25979209
TI  - A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature
      for nuclear medicine therapies with (223)Ra-, (131)I-, (177)Lu- and (111)In
      labelled radiopharmaceuticals.
AB  - The small-scale dosimetry of radionuclides in solid-tumours is directly related
      to the intra-tumoral distribution of the administered radiopharmaceutical, which
      is affected by its egress from the vasculature and dispersion within the tumour.
      The aim of the present study was to evaluate the combined dosimetric effects of
      radiopharmaceutical distribution and range of the emitted radiation in a model of
      tumour microvasculature. We developed a computational model of solid-tumour
      microenvironment around a blood capillary vessel, and we simulated the transport
      of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4
      Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion
      throughout the capillary vessel were considered. Radial dose profiles around the
      capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of
      dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose
      (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the
      250-MUm layer of tissue, were computed. The results for beta and Auger emitters
      demonstrate that the photon dose is about three to four orders of magnitude lower
      than that deposited by electrons. For (223)Ra, the beta emissions of its progeny
      deliver a dose about three orders of magnitude lower than that delivered by the
      alpha emissions. Such results may help to characterize the dose inhomogeneities
      in solid tumour therapies with radiopharmaceuticals, taking into account the
      interplay between drug distribution from vasculature and range of ionizing
      radiations.

PMID- 25979210
TI  - Low contrast detectability performance of model observers based on CT phantom
      images: kVp influence.
AB  - This paper studies low contrast detectability (LCD) performance of two model
      observers in CT phantom images acquired at different kVp levels and compares the
      results with humans in a 2-alternative forced choice experiment (2-AFC). Images
      of the Catphan phantom with objects of different contrasts (0.5 and 1%) and
      diameters (2-15 mm) were acquired in an Aquilion ONE 320-detector row CT (Toshiba
      Medical Systems, Tokyo, Japan), in two experiments, selecting (80-100-120-135 kV)
      with fixed mAs and varying the mAs to keep the dose constant, respectively. Four
      human observers evaluated the objects visibility obtaining a proportion correct
      (PC) for each case. LCD was also analyzed with two model observers (non
      prewhitening matched filter with an eye filter, NPWE, and channelized Hotelling
      observer with Gabor channels, CHO). Object contrast was affected by kV, with
      differences up to 17% between the lowest and highest kV. Both models
      overestimated human performance and were corrected by efficiency and internal
      noise factors. The NPWE model reproduced better the human PC values trends
      showing Pearson's correlation coefficients >=0.976 (0.954-0.987, 95% CI) for both
      experiments, whereas for CHO they were >=0.706 (0.493-0.839). Bland-Altman plots
      showed better agreement between NPWE and humans being the average difference
      Delta and the range of the differences Delta+/-2sigma (sigma, standard deviation)
      of Delta=-0.3%, Delta+/-2sigma = [-4.0%,4.5%]. For CHO, Delta=-1.2%, Delta+/-
      2sigma= [-10.7%,8.3%]. The NPWE model can be a useful tool to predict human
      performance in CT low contrast detection tasks in a standard phantom and be
      potentially used in protocol optimization based on kV selection.

PMID- 25979211
TI  - Performance comparison of two resolution modeling PET reconstruction algorithms
      in terms of physical figures of merit used in quantitative imaging.
AB  - PURPOSE: Resolution modeling (RM) of PET systems has been introduced in iterative
      reconstruction algorithms for oncologic PET. The RM recovers the loss of
      resolution and reduces the associated partial volume effect. While these methods
      improved the observer performance, particularly in the detection of small and
      faint lesions, their impact on quantification accuracy still requires thorough
      investigation. The aim of this study was to characterize the performances of the
      RM algorithms under controlled conditions simulating a typical (18)F-FDG
      oncologic study, using an anthropomorphic phantom and selected physical figures
      of merit, used for image quantification. METHODS: Measurements were performed on
      Biograph HiREZ (B_HiREZ) and Discovery 710 (D_710) PET/CT scanners and
      reconstructions were performed using the standard iterative reconstructions and
      the RM algorithms associated to each scanner: TrueX and SharpIR, respectively.
      RESULTS: RM determined a significant improvement in contrast recovery for small
      targets (<=17 mm diameter) only for the D_710 scanner. The maximum standardized
      uptake value (SUVmax) increased when RM was applied using both scanners. The
      SUVmax of small targets was on average lower with the B_HiREZ than with the
      D_710. Sharp IR improved the accuracy of SUVmax determination, whilst TrueX
      showed an overestimation of SUVmax for sphere dimensions greater than 22 mm. The
      goodness of fit of adaptive threshold algorithms worsened significantly when RM
      algorithms were employed for both scanners. CONCLUSIONS: Differences in general
      quantitative performance were observed for the PET scanners analyzed.
      Segmentation of PET images using adaptive threshold algorithms should not be
      undertaken in conjunction with RM reconstructions.

PMID- 25979212
TI  - Unusual Shape of Esophageal Stricture After Use of Nasogastric Tube.

PMID- 25979213
TI  - Stauffer's Syndrome Variant as an Unusual Case of Painless Jaundice.

PMID- 25979214
TI  - A Rare, Gastric, Multiseptated Duplication Cyst Resembling Gastric Lymphangioma.

PMID- 25979215
TI  - Renal tract abnormalities missed in a historical cohort of young children with
      UTI if the NICE and AAP imaging guidelines were applied.
AB  - OBJECTIVE: In a historical cohort of children with a urinary tract infection
      (UTI) who had already undergone all the imaging procedures, the aim was to
      determine renal tract abnormalities which would have been missed had we
      implemented the new guidelines from the National Institute for Health and Care
      Excellence in the United Kingdom (NICE) or the American Academy of Pediatrics
      (AAP). MATERIAL AND METHODS: After a UTI episode, forty-three children (28
      females, 65%) aged between 2 months and 2 years presenting at two general
      hospitals with a febrile UTI before 2008 underwent all the recommended imaging
      studies predating the new guidelines. Hydronephrosis was defined and graded
      according to the Society for Fetal Urology (SFU) classification. Hydronephrosis
      grade II (mild pelvicalyceal dilatation), grade III (moderate dilatation), and
      grade IV (gross dilatation with thinning of the renal cortex), duplication,
      vesicoureteral reflux (VUR) grade II and above, renal scarring and reduced renal
      uptake (<45%) on technetium-99m-labeled dimercaptosuccinic acid (DMSA)
      scintigraphy were considered significant abnormalities. We calculated the
      proportion of abnormalities which would have been missed had the new guidelines
      been used instead. RESULTS: The median of age was 7.6 months (mean 8.7, range 2
      24 months), with the majority (n = 37, 86%) being under 1 year of age. Ultrasound
      (US) showed hydronephrosis in 14 (32%), all grade II. A voiding cystourethrogram
      (VCUG) was performed in all and showed VUR >= grade II in 16 (37%), including
      eight children (19%) where it was bilateral. DMSA scan showed scarring in 25
      children (58%) of whom 11 (26%) had bilateral scars. Reduced differential renal
      uptake was present in 10 children (23%). Of the 29 children with normal US, 18
      (62%) had renal scarring and nine (31%) had VUR >= grade II. The NICE guidelines
      would have missed 63% of the children with VUR >= grade II, including a high
      proportion of grades IV and V VUR, 44% of the children with renal scarring, and
      20% of the children with decreased renal uptake, including some children with
      bilateral renal scarring and with decreased renal uptake. The AAP guidelines
      would have missed 56% of the children with VUR >= grade II, including a high
      proportion of grades IV and V VUR, and all children with renal scarring as well
      as those with decreased renal uptake. CONCLUSION: The prevalence of renal tract
      abnormalities missed by the new guidelines is high. They should be used with full
      awareness of their limitations.

PMID- 25979216
TI  - Commentary to 'Adenotonsillectomy improves quality of life in children with
      nocturnal enuresis and sleep-disordered breathing'.

PMID- 25979217
TI  - Management of refractory overactive bladder in children by transcutaneous
      posterior tibial nerve stimulation: A controlled study.
AB  - OBJECTIVE: To assess the objective efficacy of transcutaneous posterior tibial
      nerve stimulation in children presenting with overactive bladder resistant to
      well conducted treatment. MATERIAL AND METHOD: This was a randomized, double
      blind, controlled study on 20 children with OAB. All patients were previously
      treated with anticholinergic drugs associated with detrusor rehabilitation, diet
      advice, bladder-voiding hygiene and constipation treatment, with poor clinical
      results. Patients were randomized into two groups: -Group A: treatment with PTNS
      (n = 11). -Group B: sham treatment (n = 9). The program lasted 12 consecutive
      weeks with two 30-minutes sessions a week. Each patient underwent pre-stimulation
      urodynamic testing to validate bladder overactivity followed by a post
      stimulation testing. Pre- and post-stimulation urodynamic parameters were
      compared in order to objectively evaluate the treatment's efficacy. The patients
      noted their incontinence episodes for 7 consecutive days in a diary before the
      beginning of the program, in the middle and at the end of it: this led to
      computing an incontinence score (score ranged from 0 to 13, from good to poor).
      The difference between the pre-stimulation and post-stimulation score enabled to
      express clinical results in terms of poor (less than a 3-point decrease), medium
      (a 3 to 5-point decrease), good (6 to 8-point decrease), very good (final score
      ranged between 0 and 3). Children were questioned regarding their impression of
      being stimulated or not. RESULTS: In Group A, there were five very good clinical
      results (45%), one medium (10%) and five poor results (45%). In group B, nine
      very good results (66%) and three poor results (33%) were noted. Regarding
      urodynamic testing, volume voided during urgency (184 mL to 265 mL), maximal
      cystomanometry volume (215 mL to 274 mL) and volume at the onset of the first
      overactive detrusor contraction (ODC) (48 mL to 174 mL) were significantly
      increased in Group A (p = 0.002, p = 0.024 and p = 0.001) and maximal bladder
      pressure during ODC had decreased (61 to 46) (p = 0.042). 85% children in group A
      thought they were being stimulated vs. 70% in group B. CONCLUSION: Even though we
      noticed urodynamics improvements in group A, which objectively supports the
      efficacy of TCTPNS, clinical results remained the same between the two groups. In
      spite of the small size of our sample, this underlines the placebo effect of any
      type management in this pediatric population. Studying precisely the maximal
      useful voltage and duration of stimulation should then be relevant in order to
      yield maximal benefits from this easy-to-use procedure.

PMID- 25979218
TI  - Reliance of preoperative scrotal examination versus final operative findings in
      the evaluation of non-palpable testes.
AB  - OBJECTIVE: The current study evaluates whether the preoperative scrotal
      examination in children with non-palpable testes is sufficient in all cases or if
      laparoscopy is necessary to confirm the examination findings. Are the findings
      different amongst physicians depending on their level of experience? MATERIALS
      AND METHODS: This retrospective study was done between October 2009 and May 2013.
      Children with non-palpable testes underwent an examination under anesthesia prior
      to surgery to feel for a testis or nubbin, followed by a diagnostic laparoscopy
      to validate the scrotal examination. The test was considered correct if the
      laparoscopic findings supported the scrotal examination. It was considered
      incorrect if laparoscopy revealed a different finding. RESULTS: A total of 74
      testes were evaluated. All patients underwent examination under anesthesia by the
      surgeon and senior resident. The findings were recorded separately. Despite
      careful examination by experienced surgeons under anesthesia, the scrotal
      examination was incorrect in 14 patients. Four viable testes would have been
      missed if laparoscopy had not been performed. CONCLUSION: Laparoscopy should be
      considered in case of palpable scrotal nubbins to ensure no testis is left within
      the abdominal cavity.

PMID- 25979219
TI  - Transperitoneal versus retroperitoneal laparoscopic pyeloplasty in children:
      Randomized clinical trial.
AB  - INTRODUCTION: Laparoscopic pyeloplasty achieves good cosmetic and functional
      outcomes. Both transperitoneal and retroperitoneal approaches are used. No single
      study to date has compared the two approaches in a prospective randomized design.
      OBJECTIVE: We present a prospective randomized comparison between both approaches
      in children in a trial to define which technique is better with regard to
      multiple factors including operative time, hospital stay, recovery of bowel
      movement, analgesic requirement and complication rate. STUDY DESIGN: In the
      period from June 2010 to September 2012, 38 children (25 boys and 13 girls) were
      operated laparoscopically. Children were randomized into Group I (19 children)
      operated by the transperitoneal approach, and Group II (19 children) operated by
      the retroperitoneal approach. Both groups were compared as regards to the
      operative time, anesthetic changes, and postoperative recovery. A minimum sample
      size required was calculated to be 19 for each arm based on previous studies of
      laparoscopic pyeloplasty, using a mean difference in operative time = 40 min,
      effect size = 0.95, an alpha of 0.05 and power 80% and an online sample size
      calculator. Statistical analysis was performed using SPSS software using the
      Fischer exact test, chi square test and Mann-Whitney U test. The operative time
      was the primary endpoint for comparison between both approaches. RESULTS: 
      DISCUSSION: Our series is the first in the literature that compares in a
      prospective randomized design the transperitoneal and retroperitoneal
      laparoscopic pyeloplasty in children. Shouma et al. is the only prospective
      randomized study to compare both techniques in adult pyeloplasty. They had a
      significantly shorter operative time in the transperitoneal group however, the
      author in the discussion mentioned that he was at the start of the learning curve
      for retroperitonoscopic pyeloplasty when he conducted his study, which affected
      the result of the operative time. Hence, as mentioned above, we stressed the
      importance of a single surgeon with adequate equal experience in both techniques.
      The recovery of the intestinal motility and start of oral feeding were
      significantly faster in the retroperitoneal group compared to the transperitoneal
      group. In our opinion this can be explained by the absence of intraperitoneal
      manipulations and urine leakage in the peritoneal space. In their series of
      retroperitoneal pyeloplasty, El Ghoneimi et al. reported feeding after a mean of
      1.4 days, however, in our series there was even earlier oral feeding. Shouma et
      al. reported no significant difference in the start of oral feeding in their
      adult series. The limitations of our study are: the choice of the 40 min
      difference created a statistically significant difference in operative time
      between the groups which might not be considered a truly clinically important
      difference. In addition, the single author operating for both approaches, which
      might create a bias, however the author has sufficient experience in both
      approaches. Moreover, although there were significant differences in hospital
      stay and intestinal movement between the two groups, it is not clear if these
      were of clinical significance. CONCLUSION: Both transperitoneal and
      retroperitoneal approaches have high success rate. The shorter operative time,
      shorter hospital stay, rapid recovery of intestinal movement and early resumption
      of oral feeding are in favor with the retroperitoneal approach.

PMID- 25979220
TI  - Hepatocellular Carcinoma: Review of Epidemiology, Screening, Imaging Diagnosis,
      Response Assessment, and Treatment.
AB  - Hepatocellular carcinoma is a common malignancy for which prevention, screening,
      diagnosis, treatment, and surveillance demand a multidisciplinary approach.
      Knowledge of the underlying pathophysiology as well as advances in clinical
      management should be employed by radiologists to effectively communicate with
      hepatologists, surgeons, and oncologists. In this review article, we present
      recent developments in the clinical management of hepatocellular carcinoma.

PMID- 25979221
TI  - Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute
      infection in naive adult woodchucks.
AB  - Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of
      HBV infection. Currently, most infections are conducted using strains WHV7 or
      WHV8 that have very high sequence identity. This study focused on natural strain
      WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks
      inoculated with WHVNY developed productive acute infection with long lasting
      viremia. However, only one of two woodchucks infected with WHV7 at the same
      multiplicity demonstrated productive liver infection. Quantification of
      intracellular WHV RNA and DNA replication intermediates; percentages of core
      antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains
      WHVNY and WHV7 displayed comparable replication levels and capacities to induce
      acute infection in naive adult woodchucks. Strain WHVNY was therefore validated
      as valuable reagent to analyze the mechanism of hepadnavirus infection,
      especially in co- and super-infection settings, which required discrimination
      between two related virus genomes replicating in the same liver. 

PMID- 25979222
TI  - Measuring movement symmetry using tibial-mounted accelerometers for people
      recovering from total knee arthroplasty.
AB  - BACKGROUND: The purpose of this investigation was to examine movement symmetry
      changes over the first 26weeks following unilateral total knee arthroplasty in
      community environments using skin-mounted tibial accelerometers. Comparisons to
      healthy participants of similar age were also made. METHODS: Patients (N=24) with
      unilateral knee osteoarthritis (mean (SD), 65.2 (9.2) years) scheduled to undergo
      total knee arthroplasty and a control group (N=19 healthy people; mean (SD), 61.3
      (9.2) years) were recruited. The total knee arthroplasty group participated in a
      standardized course of physical rehabilitation. Tibial acceleration data were
      recorded during a Stair Climb Test and 6-Minute Walk Test. Tibial acceleration
      data were reduced to initial peak acceleration for each step. An inter-limb
      absolute symmetry index of tibial initial peak acceleration values was
      calculated. FINDINGS: The total knee arthroplasty group had greater between limb
      asymmetry for tibial initial peak acceleration and initial peak acceleration
      absolute symmetry index values five weeks after total knee arthroplasty, during
      the Stair Climb Test and the 6-Minute Walk Test. INTERPRETATION: Tibial
      accelerometry is a potential tool for measuring movement symmetry following
      unilateral total knee arthroplasty in clinical and community environments.
      Accelerometer-based symmetry outcomes follow patterns similar to published
      measures of limb loading recorded in laboratory settings.

PMID- 25979223
TI  - Passive lumbar tissue loading during trunk bending at three speeds: An in vivo
      study.
AB  - BACKGROUND: Low back disorders are closely related with the magnitude of
      mechanical loading on human spine. However, spinal loading contributed by the
      lumbar passive tissues is still not well understood. In this study, the effect of
      motion speed on lumbar passive moment output was investigated. In addition, the
      increase of lumbar passive moment during trunk bending was modeled. METHODS:
      Twelve volunteers performed trunk-bending motions at three different speeds.
      Trunk kinematics and muscle activities were collected and used to estimate
      instantaneous spinal loading and the corresponding lumbar passive moment. The
      lumbar passive moments at different ranges of trunk motion were compared at
      different speed levels and the relationship between lumbar passive moment lumbar
      flexion was modeled. FINDINGS: A non-linear, two-stage pattern of increase in
      lumbar passive moment was evident during trunk flexion. However, the effect of
      motion speed was not significant on lumbar passive moments or any of the model
      parameters. INTERPRETATION: As reported previously, distinct lumbar ligaments may
      begin to generate tension at differing extents of trunk flexion, and this could
      be the cause of the observed two-stage increasing pattern of lumbar passive
      moment. The current results also suggest that changes in tissue strain rate may
      not have a significant impact on the total passive moment output at the
      relatively slow trunk motions examined here.

PMID- 25979224
TI  - Factors facilitating patient satisfaction among women with medically unexplained
      long-term fatigue: A relational perspective.
AB  - Bodily conditions that are difficult to identify, explain and treat with the aid
      of medical knowledge and technology appear to be particularly challenging to
      medical encounters. Patients are often dissatisfied with the help they receive,
      and they often experience that their medical needs are not met. To explore
      factors facilitating patient satisfaction among patients with a medically
      unexplained condition, we ask: what is the importance of individual versus
      relational factors in facilitating patient satisfaction in clinical encounters
      between general practitioners (GPs) and women with medically unexplained long
      term fatigue? We approach this question through a statistical analysis of survey
      data collected from a net sample of 431 women recruited through a patient
      organisation for people suffering from myalgic encephalomyelitis in 2013.
      Participants were asked about their experiences with general practitioners in the
      Norwegian national health system in two different phases: shortly after illness
      onset, and current regular general practitioner last 12 months. The questions
      evolved around themes concerning shared understanding and decision making, being
      taken seriously, being paid due respect and being treated as an equal partner.
      Through descriptive statistics and multivariable logistic regression analyses, we
      explored how their experiences were related to individual and relational factors,
      respectively. Free-text comments from the questionnaires were used while
      interpreting the results. The analysis illuminates that relational aspects in
      medical encounters between GPs and ME patients, especially continuity, congruence
      in doctor-patient views and being seen by a specialist, are important catalysts
      of patient satisfaction. The probability of being satisfied with the initial
      investigation was more than six times higher in women who were referred to
      specialists, compared to those who were not. We conclude that continuity of care
      and experiences of being in a partnership that operates on a common ground - a
      shared understanding of the patient's illness - foster patient satisfaction among
      women with medically unexplained long-term fatigue.

PMID- 25979225
TI  - Ending "corrupt" practices in medicine: Harvard conference report.

PMID- 25979226
TI  - Quality assessment of orthodontic radiography in children.
AB  - OBJECTIVES: Numbers of dental panoramic tomographs (DPTs) and lateral
      cephalometric radiographs (LCRs) outweigh other radiographic examinations in 7-
      to 12-year-old Finns. Orthodontists and general practitioners (GPs) involved in
      orthodontics hold therefore the highest responsibility of the exposure of
      children to ionising radiation with its risks. Against this background, lack of
      reports on the quality of orthodontic radiography is surprising. The purpose of
      our study was to shed some light and draw the awareness of the orthodontic
      community on the subject by analyzing the quality of orthodontic radiography in
      Oral Healthcare Department of City of Helsinki, in the capital of Finland.
      MATERIALS AND METHODS: We analyzed randomly selected 241 patient files with DPTs
      and 118 patient files with LCRs of 7- to 12-year-olds for the indications of
      radiography, quality of referrals, status of interpretation, and number of failed
      radiographs. RESULTS: The majority of DPTs (95%) and all LCRs had been ordered
      for orthodontic reasons. Of the DPTs, 60% were ordered by GPs, and of the LCRs,
      64% by orthodontists. The referrals were adequate for most DPTs (78%) and LCRs
      (73%), orthodontists being responsible for the majority of inadequate referrals.
      Of the DPTs, 80% had been interpreted. Of the LCRs, 65% lacked interpretation,
      but 67% had been analysed cephalometrically. Failed radiographs, leading to
      repeated exposure, were found in 2-3%. CONCLUSION: The quality assessment
      revealed that orthodontic radiography may not completely fulfill the criteria of
      good practice. Our results stress further need of continuing education in
      radiation protection among both orthodontists and GPs involved in orthodontics.

PMID- 25979227
TI  - Diffusion tensor imaging of lumbar spinal nerve in subjects with degenerative
      lumbar disorders.
AB  - Recently several authors have reported that diffusion tensor imaging (DTI) might
      provide a new understanding of sciatica. The purpose of this study was to
      investigate the clinical feasibility of DTI for the evaluation of lumbar spinal
      nerve of patients with sciatica associated with lumbar degenerative disorders.
      Thirty-four patients (25men, mean age63. 3years) with degenerated lumbar disease,
      14 patients with lumbar spinal stenosis with foraminal stenosis, 12 with lumbar
      spinal stenosis without foraminal stenosis, five with lumbar disc herniation, two
      with discogenic low back pain, and one with spondylolysis who underwent 3.0T
      magnetic resonance (MR) imaging and surgical treatment were included in the
      present study. Fractional anisotropy (FA) was calculated from an FA map, and
      tractography was investigated. In asymptomatic nerves, tractography showed all L3
      S1 spinal nerve roots clearly. Abnormalities of tractography were classified into
      three types by shape; "Disrupted", "Narrowing", and "Tapering". More
      abnormalities of tractography were found in patients with lumbar spinal stenosis,
      and especially in patients with foraminal stenosis. The disrupted type was the
      most common. The mean FA of entrapped symptomatic nerves was less than seen on
      the intact side. This study demonstrates that tractography shows abnormal
      findings for nerve roots in lumbar spinal degeneration and that FA decreases in
      symptomatic roots. DTI may offer not only morphological evaluation, but also
      quantitative evaluation. We believe that DTI can be used as a tool for the
      diagnosis of lumbar spinal degenerative disease. 

PMID- 25979228
TI  - The BH3-mimetic obatoclax reduces HIF-1alpha levels and HIF-1 transcriptional
      activity and sensitizes hypoxic colon adenocarcinoma cells to 5-fluorouracil.
AB  - Activation of hypoxia-inducible factor (HIF)-1 is a feature of hypoxic solid
      tumors that has been associated with drug resistance, mainly due to disruption of
      Bcl-2 family dynamics. Resetting the balance in favor of proapoptotic family
      members is an attractive therapeutic goal that has been pursued by developing BH3
      mimetic compounds. In the present study we evaluated the response of human colon
      adenocarcinoma cells to the BH3-mimetic obatoclax (OBX), in terms of growth
      arrest, apoptosis and autophagy, in the presence or absence of HIF-1alpha
      stabilizing conditions; its possible effect on HIF-1alpha expression and HIF-1
      activity; and the possibility to improve the response of colon cancer cells to
      cytotoxic chemotherapeutics by combining them with OBX. Colon cancer cell
      response to the BH3-mimetic was unmodified by HIF-1 activation and OBX induced a
      decrease in HIF-1alpha protein levels and HIF-1 transcriptional activity,
      probably by decreasing HIF-1alpha synthesis and facilitating a VHL-independent
      proteasomal degradation pathway. Finally, a chemosensitizing effect of OBX with
      respect to 5-fluorouracil or oxaliplatin treatment was observed, highlighting the
      possibility that patients with hypoxic colon tumors might benefit from combined
      regimens including OBX. 

PMID- 25979229
TI  - Lipid mediator lipoxin A4 inhibits tumor growth by targeting IL-10-producing
      regulatory B (Breg) cells.
AB  - Lipoxin A4 (LXA4), an arachidonic acid-derived anti-inflammatory lipid mediator,
      shows anti-tumor potential by regulating tumor immune microenvironments. However,
      the underlying molecular and cellular basis of this function remains unclear. IL
      10-producing B (Breg) cells display tumor-promoting effects by negatively
      regulating anti-tumor immunity. Here we show that LXA4 inhibits tumor growth by
      suppressing the generation of Breg cells in tumor-bearing mice. The
      administration of LXA4 inhibited the induction of Breg cells. Breg cell
      deficiency, in turn, resulted in LXA4 losing its anti-tumor properties.
      Intriguingly, regulatory T (Treg) cells also had a role in this process.
      Targeting Breg cells by LXA4 decreased the number of Treg cells in draining lymph
      nodes and tumor tissues as well as enhanced cytotoxic T cell activities. In
      addition, we further demonstrated that LXA4 inhibited Breg cells through its
      dephosphorylating STAT3 and ERK. These findings unveil a new anti-tumor mechanism
      underlying LXA4 targeting Breg cells with potential clinical applications. 

PMID- 25979231
TI  - The infiltration and functional regulation of eosinophils induced by TSLP promote
      the proliferation of cervical cancer cell.
AB  - Cervical cancer is often associated with eosinophil (EOS) infiltration, but the
      source and the role of EOS are still largely unknown. Our previous work has
      established that thymic stromal lymphopoietin (TSLP) can stimulate the growth of
      cervical cancer cell in an autocrine manner. Here, we report that EOS
      infiltration of the lesion site increased gradually with the progression of
      cervical cancer. The increase in TSLP secretion in HeLa and SiHa cells induced by
      hypoxia led to a high level of chemokine CCL17 production by HeLa and SiHa cells,
      and recruited more EOS to the cancer lesion. In addition, TSLP derived from HeLa
      and SiHa cells promoted proliferation, up-regulated the levels of anti
      inflammatory cytokines (IL-10, IL-4, IL-5 and IL-13), and decreased the
      expression of CD80 and CD86 of EOS. Such educated EOS significantly promoted
      proliferation and restricted the apoptosis of cervical cancer cells, which was
      associated with the up-regulation of Ki-67, PCNA and Bcl-2, and the down
      regulation of Fas and FasL in HeLa and SiHa cells. These results suggest that a
      high level of TSLP in cancer lesions mediated by hypoxia is an important
      regulator of the progression of cervical cancer by recruiting and licensing tumor
      associated EOS to promote the growth of the cervical cancer cell itself. This
      provides a scientific basis on which potential therapeutic strategies could be
      targeted to cervical cancer, especially for patients with massive infiltrations
      of EOS. 

PMID- 25979230
TI  - Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal
      liver metastases, and is clinically safe and tolerable in combination with FOLFOX
      chemotherapy.
AB  - In vitro and pre-clinical studies have suggested that addition of the diet
      derived agent curcumin may provide a suitable adjunct to enhance efficacy of
      chemotherapy in models of colorectal cancer. However, the majority of evidence
      for this currently derives from established cell lines. Here, we utilised patient
      derived colorectal liver metastases (CRLM) to assess whether curcumin may provide
      added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in cancer stem
      cell (CSC) models. Combination of curcumin with FOLFOX chemotherapy was then
      assessed clinically in a phase I dose escalation study. Curcumin alone and in
      combination significantly reduced spheroid number in CRLM CSC models, and
      decreased the number of cells with high aldehyde dehydrogenase activity
      (ALDH(high)/CD133(-)). Addition of curcumin to oxaliplatin/5-FU enhanced anti
      proliferative and pro-apoptotic effects in a proportion of patient-derived
      explants, whilst reducing expression of stem cell-associated markers ALDH and
      CD133. The phase I dose escalation study revealed curcumin to be a safe and
      tolerable adjunct to FOLFOX chemotherapy in patients with CRLM (n = 12) at doses
      up to 2 grams daily. Curcumin may provide added benefit in subsets of patients
      when administered with FOLFOX, and is a well-tolerated chemotherapy adjunct. 

PMID- 25979232
TI  - Interleukin-8 upregulates integrin beta3 expression and promotes estrogen
      receptor-negative breast cancer cell invasion by activating the PI3K/Akt/NF
      kappaB pathway.
AB  - Interleukin-8 (IL-8) possesses tumorigenic and proangiogenic properties and is
      overexpressed in many human cancers. The integrin family regulates a diverse
      array of cellular functions crucial to the initiation, progression and metastasis
      of solid tumors. However, the mechanisms of action of IL-8 and integrin in
      estrogen receptor-negative breast cancer are largely unknown. In this study, IL-8
      and integrin beta3 expression in human breast cancer cells and tissues was
      examined by real-time PCR, Western blot and immunochemistry analysis. Integrin
      beta3 expression, invasive ability and the activation of PI3K/Akt and NF-kappaB
      pathways in IL-8 knockdown breast cancer cells were evaluated. In addition,
      reporter assay and ChIP were performed to assess integrin beta3 promoter activity
      in IL-8 knockdown cells. We observed a positive correlation between integrin
      beta3 and IL-8 expression, which was inversely correlated with ER status in
      breast cancer cell lines and tissues. IL-8 siRNA decreased the invasion and
      integrin beta3 expression in human breast cancer cells. Moreover, IL-8 siRNA
      attenuated the phosphorylation of PI3K and Akt and inhibited NF-kappaB activity
      and binding on integrin beta3 promoter. IL-8 siRNA diminished NF-kappaB nuclear
      translocation via blocking IkappaB phosphorylation in the cytoplasm. In
      conclusion, IL-8 activates the PI3K/Akt pathway, which in turn activates NF
      kappaB, resulting in the upregulation of integrin beta3 expression and increased
      invasion of estrogen receptor-negative breast cancer cells. IL-8/PI3K/Akt/NF
      kappaB/integrin beta3 axis may be exploited for therapeutic intervention to
      breast cancer metastasis. 

PMID- 25979233
TI  - Cancer stem cells and their vascular niche: Do they benefit from each other?
AB  - Cancer stem cells (CSCs) locate in and interact with particular vascular niches
      to maintain their stemness. CSCs induce, remodel and participate in the formation
      of microenvironmental niches to facilitate survival, stemness and escape from
      radio-/chemo-/bio-therapies. Neovasculature in tumor is often basement membrane
      deficient and enriched with CSC-derived endothelial cells (ECs) and other mural
      cells, which may promote tumor invasion and metastasis. The aim of this review is
      to summarize recent findings about the crosstalk between CSCs and their vascular
      niches and discuss the potential therapeutic significance.

PMID- 25979235
TI  - Regulation and function of tetrapyrrole biosynthesis in plants and algae.
AB  - Tetrapyrroles are macrocyclic molecules with various structural variants and
      multiple functions in Prokaryotes and Eukaryotes. Present knowledge about the
      metabolism of tetrapyrroles reflects the complex evolution of the pathway in
      different kingdoms of organisms, the complexity of structural and enzymatic
      variations of enzymatic steps, as well as a wide range of regulatory mechanisms,
      which ensure adequate synthesis of tetrapyrrole end-products at any time of
      development and environmental condition. This review intends to highlight new
      findings of research on tetrapyrrole biosynthesis in plants and algae. In the
      course of the heme and chlorophyll synthesis in these photosynthetic organisms,
      glutamate, one of the central and abundant metabolites, is converted into highly
      photoreactive tetrapyrrole intermediates. Thereby, several mechanisms of
      posttranslational control are thought to be essential for a tight regulation of
      each enzymatic step. Finally, we wish to discuss the potential role of
      tetrapyrroles in retrograde signaling and point out perspectives of the formation
      of macromolecular protein complexes in tetrapyrrole biosynthesis as an efficient
      mechanism to ensure a fine-tuned metabolic flow in the pathway. This article is
      part of a Special Issue entitled: Chloroplast Biogenesis. 

PMID- 25979236
TI  - An automated phenotype-based microscopy screen to identify pro-longevity
      interventions acting through mitochondria in C. elegans.
AB  - Mitochondria are multifunctional organelles that play a central role in cellular
      homeostasis. Severe mitochondrial dysfunction leads to life-threatening diseases
      in humans and accelerates the aging process. Surprisingly, moderate reduction of
      mitochondrial function in different species has anti-aging effects. High
      throughput screenings in the nematode Caenorhabditis elegans lead to the
      identification of several pro-longevity genetic and pharmacological
      interventions. Large-scale screens, however, are manual, subjective, time
      consuming and costly. These limitations could be reduced by the identification of
      automatically quantifiable biomarkers of healthy aging. In this study we exploit
      the distinct and reproducible phenotypes described in C. elegans upon different
      levels of mitochondrial alteration to develop an automated high-content strategy
      to identify new potential pro-longevity interventions. Utilizing the microscopy
      platform Cellomics ArrayScan Reader, we optimize a workflow to automatically and
      reliably quantify the discrete phenotypic readouts associated with different
      degrees of silencing of mitochondrial respiratory chain regulatory proteins, and
      validate the approach with mitochondrial-targeting drugs known to extend lifespan
      in C. elegans. Finally, we report that a new mitochondrial ATPase modulator
      matches our screening phenotypic criteria and extends nematode's lifespan thus
      providing the proof of principle that our strategy could be exploited to identify
      novel mitochondrial-targeted drugs with pro-longevity activity. This article is
      part of a Special Issue entitled: Mitochondrial Dysfunction in Aging. 

PMID- 25979234
TI  - Dietary restriction, mitochondrial function and aging: from yeast to humans.
AB  - Dietary restriction (DR) attenuates many detrimental effects of aging and
      consequently promotes health and increases longevity across organisms. While over
      the last 15 years extensive research has been devoted towards understanding the
      biology of aging, the precise mechanistic aspects of DR are yet to be settled.
      Abundant experimental evidence indicates that the DR effect on stimulating health
      impinges several metabolic and stress-resistance pathways. Downstream effects of
      these pathways include a reduction in cellular damage induced by oxidative
      stress, enhanced efficiency of mitochondrial functions and maintenance of
      mitochondrial dynamics and quality control, thereby attenuating age-related
      declines in mitochondrial function. However, the literature also accumulates
      conflicting evidence regarding how DR ameliorates mitochondrial performance and
      whether that is enough to slow age-dependent cellular and organismal
      deterioration. Here, we will summarize the current knowledge about how and to
      which extent the influence of different DR regimes on mitochondrial biogenesis
      and function contribute to postpone the detrimental effects of aging on health
      span and lifespan. This article is part of a Special Issue entitled:
      Mitochondrial Dysfunction in Aging.

PMID- 25979238
TI  - Total Arch Replacement Versus More Conservative Management in Type A Acute Aortic
      Dissection.
AB  - BACKGROUND: Surgical management of aortic arch in type A acute dissection (TAAD)
      is controversial. This study compared short-term and long-term outcomes of total
      arch replacement (TAR) interventions versus more conservative arch management
      (CAM). METHODS: Between 1997 and 2012, 240 patients underwent TAAD surgery in our
      institution; 53 (22.1%) received TAR and 187 (77.9%) received CAM. Compared with
      CAM patients, those undergoing TAR were younger (59.1 vs 64.4 years, p = 0.004)
      and were less likely to present with cardiogenic shock (3.8 vs 14.4, p = 0.02).
      Distal site of intimal tear (arch or descending aorta) was predictive of TAR
      management (odds ratio [OR], 9.1; p < 0.001). RESULTS: Hospital mortality was
      similar in the groups (24.1% vs 22.6%; p = 0.45), and no other significant
      differences were observed in terms of major postoperative complications. Age (OR,
      1.047; p = 0.007) and cardiopulmonary bypass time (OR, 1.005 per minute; p =
      0.05) emerged as independent predictors of hospital death. The TAR management did
      not affect hospital mortality (propensity score [PS] adjusted OR: 1.51, p =
      0.36). On Kaplan-Meier analysis, 7-year survival (TAR, 52.1% +/- 0.9% vs CAM,
      57.2% +/- 4.2%, log-rank p = 0.9) and freedom from aortic re-intervention (TAR,
      71.6% +/- 1.3% vs CAM, 85.4% +/- 3.9%, log-rank p = 0.3) were similar. The PS
      adjusted Cox regression showed no relationship between type of arch management
      and follow-up survival (hazard ratio [HR], 1.001; p = 0.8) or need for re
      intervention (HR, 1.507; p = 0.4). CONCLUSIONS: In our experience TAR and CAM
      were associated with similar hospital mortality and morbidity rates.
      Nevertheless, the more extensive arch interventions were not protective for long
      term survival and freedom from aortic re-intervention. Thus, in TAAD patients TAR
      remains indicated by site of intimal tear and patient-specific factors.

PMID- 25979239
TI  - Anemia Is a Risk Factor of New Intraoperative Hemorrhagic Stroke During Valve
      Surgery for Endocarditis.
AB  - BACKGROUND: Infective endocarditis is often associated with cerebral
      complications, the most serious of which is intraoperative hemorrhagic stroke
      owing to anticoagulation for cardiopulmonary bypass. However, its prevalence and
      risk factors are unknown. We evaluated the prevalence and risk factors of
      intraoperative hemorrhagic stroke in patients with infective endocarditis.
      METHODS: In 246 patients who underwent valve surgery for active endocarditis
      between 2005 and 2012, 127 patients had both preoperative and postoperative
      intracranial neuroimaging. The prevalence and risk factors of intraoperative
      stroke were analyzed in those 127 patients. RESULTS: Valve surgery was performed
      in 127 patients 19.6 +/- 27.1 days after infective endocarditis diagnosis.
      Fourteen experienced intraoperative hemorrhagic stroke, and 1 died. None of 29
      patients with preoperative hemorrhagic stroke showed exacerbation of hemorrhagic
      lesions, whereas 1 of 57 patients with preoperative cerebral infarction showed
      hemorrhagic transformation of infarct lesions. Thirteen of 14 hemorrhagic
      complications were new ectopic intracranial hemorrhage. Multivariate analysis
      showed not preoperative cerebral lesions but preoperative low hemoglobin level as
      the only risk factor for intraoperative hemorrhagic stroke (odds ratio, 0.51; 95%
      confidence interval, 0.26 to 0.87; p = 0.03). A preoperative hemoglobin cutoff
      value of 9.2 g/dL was determined by receiver operating curve analysis. Of 41
      patients with preoperative hemoglobin level less than 9.2 g/dL, 9 (22%) had
      intraoperative new hemorrhage, whereas 4 (5%) of 86 patients with hemoglobin
      level of at least 9.2 g/dL had ectopic new hemorrhage. CONCLUSIONS:
      Intraoperative hemorrhagic stroke was not rare, and ectopic hemorrhagic stroke,
      associated with preoperative anemia, was more prevalent than hemorrhagic
      transformation of existing cerebral lesions.

PMID- 25979240
TI  - Pericardiectomy for Constrictive Pericarditis: 20 Years of Experience at the
      Montreal Heart Institute.
AB  - BACKGROUND: The aim of this study was to evaluate our single-center experience
      with pericardiectomy for constrictive pericarditis. The main objectives of our
      analysis were long-term survival, clinical outcome, and identification of risk
      factors. METHODS: Over a 20-year period, 99 consecutive patients underwent
      pericardiectomy at the Montreal Heart Institute. The indications for operation
      were idiopathic pericarditis (61%), postsurgical (13%), infectious (15%),
      postirradiation (2%), and miscellaneous (9%). Associated procedures were
      performed in 36% of cases. The duration of symptoms was longer than 6 months in
      53% of cases, and two thirds of patients were in New York Heart Association class
      III or IV. RESULTS: Hospital mortality was 9% in the whole series and 7.9% in
      case of isolated pericardiectomy. The patients operated on within 6 months after
      the onset of symptoms showed a lower risk of mortality. Conversely, preoperative
      hepatomegaly and concomitant valvular operation were associated with
      significantly higher mortality on both univariate and multivariate analysis. In
      cases of isolated pericardiectomy, the outcome was mainly conditioned by
      associated comorbidities. The long-term survival was satisfactory, and the
      functional status at follow-up was improved in most cases. CONCLUSIONS: The
      clinical outcome of pericardiectomy for constrictive pericarditis is still marked
      by high operative mortality. Nevertheless, surgical treatment is able to improve
      the functional class in the majority of late survivors. Preoperative clinical
      conditions and associated comorbidities are crucial in predicting the risk of
      mortality, and early operation seems to be the most appropriate choice. The most
      suitable surgical strategy in cases of associated valvular operation remains to
      be determined.

PMID- 25979241
TI  - Early Surgical Repair of the Coronary Artery Fistulae in Children: 30 Years of
      Experience.
AB  - BACKGROUND: Congenital coronary artery fistula (CAF) is a rare anomaly that may
      lead to the development of early heart failure or late complications. We reviewed
      our experience and outcomes of surgically corrected CAF. METHODS: From June 1982
      to October 2012, 13 children aged between 3 days and 5.2 years (median 13.9
      months) underwent repair of CAF. Four patients (30.8%) presented with congestive
      heart failure. Both coronary arteries were affected with equal incidence. All
      patients underwent preoperative cardiac catheterization. Repair was undertaken
      with cardiopulmonary bypass in 10 patients (76.9%), and 5 patients (38.5%) had
      concomitant repair of associated cardiac lesions. Seven patients (53.8%)
      underwent epicardial closure, and in 6 patients (46.2%),
      transcoronary/endocardial closure was used. RESULTS: There were no early or late
      deaths. Transient myocardial ischemia occurred in 2 patients (14.4%). One patient
      (7.7%) underwent reoperation (aortic valve repair) for a bicuspid aortic valve,
      22 years after initial surgery. Follow-up data were complete for 12 patients
      (92.3%), with a median follow-up of 6 years (range, 1 month to 31 years). All
      patients were in New York Heart Association class I with no symptoms. There were
      no long-term cardiovascular sequelae, and no patient required coronary
      reintervention. CONCLUSIONS: Early surgical repair of CAF in children can be
      performed safely and carries an excellent long-term prognosis.

PMID- 25979242
TI  - Developing a DNA methylation assay for human age prediction in blood and
      bloodstain.
AB  - Age prediction of an individual based on biological traces remained in a crime
      scene is of ultimate importance for criminal investigation. Growing evidence
      indicates that some CpG sites may have age-related methylation changes and thus
      may be a promising tool for age prediction. In this study, we utilized the
      pyrosequencing approach to screen age-related CpG (AR-CpG) sites for age
      prediction. Five AR-CpGs were identified as age-related markers from thirty-eight
      candidates, among which three CpG sites, ITGA2B_1, NPTX2_3, and NPTX2_4 were
      never reported in previous studies. We fit a linear regression model for age
      prediction based on methylation assay for 89 blood samples from donors aged 9-75
      years old. The model included four AR-CpG markers in three gene fragments ASPA,
      ITGA2B and NPTX2 and enabled the age prediction with R(2)=0.819. The mean
      absolute deviation (MAD) from chronological age of the model was 7.870. We
      validated the linear regression model with a validation set of 40 blood samples,
      and the prediction MAD was 7.986. There was no statistically significant
      difference in age prediction between 20 pairs of blood samples and bloodstains.
      Six pairs of fresh and old bloodstains were analyzed using our assay. The
      obtained results showed the assay still performed an effective prediction on
      bloodstains after four-month storage in room conditions. This study indicates
      that our DNA methylation assay is a reliable and effective method for age
      prediction for forensic purposes. 

PMID- 25979244
TI  - Bulky mass tumor in right foot.

PMID- 25979243
TI  - Transurethral resection of the prostate for patients with Gleason score 6
      prostate cancer and symptomatic prostatic enlargement: a risk-adaptive strategy
      for the era of active surveillance.
AB  - OBJECTIVE: To investigate whether transurethral resection of the prostate can be
      used as both (i) treatment for symptomatic prostatic enlargement in patients with
      prostate cancer and (ii) a risk-adaptive strategy for reducing prostate-specific
      antigen levels and broadening the indications of active surveillance. METHODS: We
      retrospectively reviewed data of 3680 patients who underwent prostate biopsies at
      a single institution (March 2006 to January 2012). Of 529 men who had Gleason
      score 6 prostate cancer and were ineligible for active surveillance, 86 (16.3%)
      underwent transurethral resection of the prostate for symptomatic prostatic
      enlargement. We assessed how changes in prostate-specific antigen and prostate
      specific antigen density influenced the eligibility for active surveillance and
      the outcome of subsequent therapy. The following active surveillance criteria
      were used: prostate-specific antigen <= 10 ng/ml, prostate-specific antigen
      density <= 0.15, positive cores <= 3 and single core involvement <= 50%. RESULTS:
      The median age, pre-operative prostate-specific antigen and prostate volume were
      71 years, 6.95 ng/ml, and 45.8 g, respectively. In 82.6% (71/86) of analyzed
      cases, ineligibility for active surveillance had resulted from elevated prostate
      specific antigen level or prostate-specific antigen density. With a median
      resection of 16.5 g, transurethral resection of the prostate reduced the
      percentage of prostate-specific antigen and the percentage of prostate-specific
      antigen density by 34.5 and 50.0%, respectively, making 81.7% (58/71) of the
      patients eligible for active surveillance. Prostate-specific antigen level
      remained stabilized in all (21/21) patients maintained on active surveillance
      without disease progression during the median follow-up of 50.6 months. Among
      patients who underwent radical prostatectomy, 96.7% (29/30) exhibited localized
      disease. CONCLUSIONS: Risk-adaptive transurethral resection of the prostate may
      prevent overtreatment and allay prostate-specific antigen-associated anxiety in
      patients with biopsy-proven low-grade prostate cancer and elevated prostate
      specific antigen. Additional benefits include voiding symptom improvement and the
      avoidance of curative therapy's immediate side effects.

PMID- 25979245
TI  - Are hospitals in Japan with larger patient volume treating younger and earlier
      stage cancer patients? An analysis of hospital-based cancer registry data in
      Japan.
AB  - OBJECTIVE: Differences in hospital case-mix have not been adequately accounted
      for in hospital volume and patient outcome studies in Japan. We aimed to examine
      whether differences may exist by investigating the distribution of patients'
      stage and age across designated cancer treatment hospitals of varying patient
      volume across Japan. METHODS: We analyzed data of gastric, breast, colorectal,
      lung and liver cancer patients who were included in the national database of
      hospital-based cancer registries between 2008 and 2011. We investigated the
      association between hospital volume, cancer stage and patient age. Hospitals were
      classified into five groups according to patient volume. RESULTS: In total, 676
      713 patients met the inclusion criteria. The proportion of patients with early
      stage (tumor-node-metastasis Stage 0 or I) cancer was higher among high-volume
      hospitals for all cancer types except small cell lung cancer. The proportion of
      older patients (age >75 years) was smaller among high-volume hospitals for all
      cancer types. The difference in the proportion of patients with early-stage
      cancers between very low-volume and very high-volume hospitals was greatest for
      non-small cell lung cancer (26.5% for very low and 43.5% for very high). This
      difference for the proportion of older patients was also greatest for non-small
      cell lung cancer (48.9% for very low and 30.3% for very high). CONCLUSIONS: We
      showed that the proportions of early-stage cancer patients and younger patients
      are greater in higher-volume hospitals compared with lower-volume hospitals in
      Japan. Researchers conducting volume-outcome studies and policymakers analyzing
      hospital performance should be cautious when making interhospital comparisons.

PMID- 25979246
TI  - Optimizing de novo transcriptome assembly and extending genomic resources for
      striped catfish (Pangasianodon hypophthalmus).
AB  - Striped catfish (Pangasianodon hypophthalmus) is a commercially important
      freshwater fish used in inland aquaculture in the Mekong Delta, Vietnam. The
      culture industry is facing a significant challenge however from saltwater
      intrusion into many low topographical coastal provinces across the Mekong Delta
      as a result of predicted climate change impacts. Developing genomic resources for
      this species can facilitate the production of improved culture lines that can
      withstand raised salinity conditions, and so we have applied high-throughput Ion
      Torrent sequencing of transcriptome libraries from six target osmoregulatory
      organs from striped catfish as a genomic resource for use in future selection
      strategies. We obtained 12,177,770 reads after trimming and processing with an
      average length of 97bp. De novo assemblies were generated using CLC Genomic
      Workbench, Trinity and Velvet/Oases with the best overall contig performance
      resulting from the CLC assembly. De novo assembly using CLC yielded 66,451
      contigs with an average length of 478bp and N50 length of 506bp. A total of
      37,969 contigs (57%) possessed significant similarity with proteins in the non
      redundant database. Comparative analyses revealed that a significant number of
      contigs matched sequences reported in other teleost fishes, ranging in similarity
      from 45.2% with Atlantic cod to 52% with zebrafish. In addition, 28,879 simple
      sequence repeats (SSRs) and 55,721 single nucleotide polymorphisms (SNPs) were
      detected in the striped catfish transcriptome. The sequence collection generated
      in the current study represents the most comprehensive genomic resource for P.
      hypophthalmus available to date. Our results illustrate the utility of next
      generation sequencing as an efficient tool for constructing a large genomic
      database for marker development in non-model species. 

PMID- 25979248
TI  - Is the anesthesiologist necessary in the endoscopy suite? A review of patients,
      payers and safety.
AB  - The use of propofol for sedation during endoscopy has been increasing,
      particularly given its association with superior patient satisfaction. Propofol
      sedation may also allow for higher quality endoscopy exams, increased efficiency
      of endoscopy suites and most particularly, permit better patient compliance with
      colonoscopy for colorectal cancer screening. However, propofol is typically
      provided by anesthesia specialists via monitored anesthesia care, and is
      associated with significant economic burden. Given the increasing use of
      monitored anesthesia care, which adds significant costs to endoscopy, payers are
      likely to react with changes in payer policies. One alternative to monitored
      anesthesia care is non-anesthesiologist administered propofol, which due to
      safety concerns and a lack of reimbursement has not been widely adopted in the
      US. 

PMID- 25979247
TI  - A microfibril assembly assay identifies different mechanisms of dominance
      underlying Marfan syndrome, stiff skin syndrome and acromelic dysplasias.
AB  - Fibrillin-1 is the major component of the 10-12 nm diameter extracellular matrix
      microfibrils. The majority of mutations affecting the human fibrillin-1 gene,
      FBN1, result in Marfan syndrome (MFS), a common connective tissue disorder
      characterised by tall stature, ocular and cardiovascular defects. Recently, stiff
      skin syndrome (SSS) and a group of syndromes known collectively as the acromelic
      dysplasias, which typically result in short stature, skin thickening and joint
      stiffness, have been linked to FBN1 mutations that affect specific domains of the
      fibrillin-1 protein. Despite their apparent phenotypic differences, dysregulation
      of transforming growth factor beta (TGFbeta) is a common factor in all of these
      disorders. Using a newly developed assay to track the secretion and incorporation
      of full-length, GFP-tagged fibrillin-1 into the extracellular matrix, we
      investigated whether or not there were differences in the secretion and
      microfibril assembly profiles of fibrillin-1 variants containing substitutions
      associated with MFS, SSS or the acromelic dysplasias. We show that substitutions
      in fibrillin-1 domains TB4 and TB5 that cause SSS and the acromelic dysplasias do
      not prevent fibrillin-1 from being secreted or assembled into microfibrils,
      whereas MFS-associated substitutions in these domains result in a loss of
      recombinant protein in the culture medium and no association with microfibrils.
      These results suggest fundamental differences in the dominant pathogenic
      mechanisms underlying MFS, SSS and the acromelic dysplasias, which give rise to
      TGFbeta dysregulation associated with these diseases. 

PMID- 25979249
TI  - Structural and Functional Analysis of the Signal-Transducing Linker in the pH
      Responsive One-Component System CadC of Escherichia coli.
AB  - The pH-responsive one-component signaling system CadC in Escherichia coli belongs
      to the family of ToxR-like proteins, whose members share a conserved modular
      structure, with an N-terminal cytoplasmic winged helix-turn-helix DNA-binding
      domain being followed by a single transmembrane helix and a C-terminal
      periplasmic pH-sensing domain. In E. coli CadC, a cytoplasmic linker comprising
      approximately 50 amino acids is essential for transmission of the signal from the
      sensor to the DNA-binding domain. However, the mechanism of transduction is
      poorly understood. Using NMR spectroscopy, we demonstrate here that the linker
      region is intrinsically disordered in solution. Furthermore, mutational analyses
      showed that it tolerates a range of amino acid substitutions (altering polarity,
      rigidity and alpha-helix-forming propensity), is robust to extension but is
      sensitive to truncation. Indeed, truncations either reversed the expression
      profile of the target operon cadBA or decoupled expression from external pH
      altogether. CadC dimerizes via its periplasmic domain, but light-scattering
      analysis provided no evidence for dimerization of the isolated DNA-binding
      domain, with or without the linker region. However, bacterial two-hybrid analysis
      revealed that CadC forms stable dimers in a stimulus- and linker-dependent
      manner, interacting only at pH<6.8. Strikingly, a variant with inversed cadBA
      expression profile, which lacks most of the linker, dimerizes preferentially at
      higher pH. Thus, we propose that the disordered CadC linker is required for
      transducing the pH-dependent response of the periplasmic sensor into a structural
      rearrangement that facilitates dimerization of the cytoplasmic CadC DNA-binding
      domain. 

PMID- 25979250
TI  - Development of a new risk score for hospital-associated venous thromboembolism in
      critically-ill children not undergoing cardiothoracic surgery.
AB  - BACKGROUND: Although risk of hospital-associated venous thromboembolism (HA-VTE)
      differs between critically and non-critically ill children, studies to date have
      not led to distinct, pragmatic risk scores. OBJECTIVE: To determine risk factors
      for HA-VTE in critically ill children not undergoing cardiothoracic surgery, in
      order to derive a novel HA-VTE risk score for this population. METHODS: We
      conducted a retrospective analysis from January 2006 through April 2013 at All
      Children's Hospital Johns Hopkins Medicine. HA-VTE cases were identified using
      ICD-9 discharge diagnosis codes, with subsequent validation via radiologic record
      review. Cases were restricted to Pediatric Intensive Care Unit (PICU) admissions.
      Patients who underwent cardiothoracic surgery were excluded; cardiac
      catheterization per se was not exclusionary. For each case, three non-HA-VTE PICU
      controls were randomly selected. Data were abstracted on putative risk factors,
      and associations between risk factors and HA-VTE were estimated using odds ratios
      (ORs) and 95% confidence intervals (95%CIs). RESULTS: There were 57 HA-VTE cases
      and 171 controls. HA-VTE occurrence was 3 per 1000 PICU admissions (0.3%).
      Central venous catheter (CVC) (OR:26.64; 95%CI:7.46-95.13), length of stay (LOS)
      >=4days (OR:20.22; 95%CI:2.27-180.07), and significant infection (OR:3.41;
      95%CI:1.13-10.29) were independent, statistically-significant risk factors for HA
      VTE in a multivariate model. A risk score was derived in which HA-VTE risk
      exceeded 2% (threshold for anticoagulant thromboprophylaxis in hospitalized
      adults) with a score of 15, and was >1% but <2% (risk zone for mechanical
      thromboprophylaxis in hospitalized adults) with scores of 7-14. CONCLUSION: The
      presence of a CVC, LOS>=4days and infection are significant risk factors for HA
      VTE in critically ill children not undergoing cardiothoracic surgery, forming the
      basis for a new risk score that warrants prospective validation.

PMID- 25979251
TI  - The effect of emergency presentation on surgery and survival in lung cancer
      patients in England, 2006-2008.
AB  - BACKGROUND: A large proportion of lung cancer patients in England are diagnosed
      through an emergency route, which is associated with poorer outcomes. Here, we
      investigated the association between emergency presentation and the odds of
      undergoing surgical resection and subsequent survival among lung cancer patients
      undergoing surgical resection as well as those who did not. METHODS: Details of
      93,783 lung cancers were extracted from the National Cancer Data Repository. For
      non-small cell lung cancer (NSCLC) patients we calculated odds ratios for
      undergoing surgical resection. Survival was assessed for resected NSCLC and for
      all other lung cancer patients in three different time intervals: short-term,
      intermediate and long-term. RESULTS: Compared with those who did not, NSCLC
      patients presenting through an emergency route were less likely to undergo
      surgical resection (adjusted OR=0.22, 95% CI: 0.20-0.24). Patients who underwent
      surgical resection after an emergency presentation had lower survival in the
      intermediate period (adjusted HR=1.27, 95% CI: 1.06-1.54) and long term (adjusted
      HR=1.20, 95% CI: 0.99-1.45). Among all other lung cancer patients, those
      diagnosed through an emergency route had lower survival, particularly in the
      short-term (adjusted HR=3.54, 95% CI: 3.42-3.67), but the association remained in
      the intermediate (adjusted HR=1.66, 95% CI: 1.63-1.69) and long term (adjusted
      HR=1.10, 95% CI: 1.05-1.15). CONCLUSION: The reduced access to surgical resection
      and lower survival among lung cancer patients who present through an emergency
      admission, highlights the importance of ensuring symptoms are recognised early so
      that presentation as an emergency can be reduced.

PMID- 25979252
TI  - Optimal number of needle passes in endoscopic ultrasound-guided fine needle
      aspiration for pancreatic lesions.
AB  - OBJECTIVES: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is
      accurate in cytological diagnosis of pancreatic lesions. Our aim was to determine
      optimal number of needle passes in EUS-FNA for pancreatic lesions without onsite
      cytopathologist, who is not routinely available to participate in the procedure.
      METHODS: Results of all needle passes in EUS-FNAs for 117 pancreatic neoplasms in
      115 patients were reviewed retrospectively. Factors that required 2 or more
      needle passes for correct diagnosis were identified by multivariate logistic
      regression analysis. In each lesion group defined by the factors that required 2
      or more passes and were known at the time of EUS-FNA, number of needle passes was
      regarded as optimal when an increase in diagnostic sensitivity by an additional
      needle pass did not reach 10%. RESULTS: Size of 15 mm or less (OR 4.58, 95% CI
      1.70-12.3, P < 0.01), location of head (OR 5.02, 95% CI 1.82-13.9, P < 0.01), and
      neuroendocrine tumor (NET) (OR 5.04, 95% CI 1.38-18.4, P = 0.01) independently
      required 2 or more needle passes. Optimal numbers of needle passes for lesions of
      15 mm or less in the head, those of more than 15 mm in the head, those of 15 mm
      or less in the body or tail, and those of more than 15 mm in the body or tail
      were 3, 2, 2, and 1, respectively. When these numbers of needle passes were
      performed, 93% of pancreatic lesions were correctly diagnosed. CONCLUSIONS:
      Optimal numbers of needle passes in EUS-FNA for pancreatic lesions without onsite
      cytopathologist were between 1 and 3.

PMID- 25979253
TI  - Association between apolipoprotein E gene polymorphism and depression.
AB  - We performed an updated meta-analysis to obtain a more precise estimation of the
      relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility
      to depression, as previous reports have been inconsistent. Twenty studies with
      2286 depression patients and 3845 controls were included. Odds ratios (OR) with
      95% confidence intervals (CI) were calculated to assess the association between
      ApoE gene polymorphism and depression using a random effects model. Results
      showed a significant association between ApoE gene polymorphism and
      susceptibility to depression in the overall population (epsilon2/epsilon3
      genotype versus epsilon3/epsilon3: OR 0.76, 95% CI 0.59-0.99). Subgroup analyses
      indicated an association in the Caucasian population (epsilon2 allele versus
      epsilon3: OR 0.75, 95% CI 0.58-0.97) as well as in late-life depression (LLD)
      patients (epsilon3/epsilon4 genotype versus epsilon3/epsilon3: OR 1.34, 95% CI
      1.07-1.68, and epsilon4 allele versus epsilon3: OR 1.30, 95% CI 1.06-1.59). We
      concluded that the epsilon2/epsilon3 genotype likely provided a protective effect
      against depression in the overall population and the epsilon2 allele acted as a
      protective factor for depression in the Caucasian population while the epsilon4
      allele and epsilon3/epsilon4 genotype were associated with an increased risk of
      depression in the LLD subjects. 

PMID- 25979254
TI  - Technique and early clinical outcomes for spinal and paraspinal tumours treated
      with stereotactic body radiotherapy.
AB  - We report technique and early clinical results of stereotactic body radiotherapy
      (SBRT) from Princess Alexandra Hospital. SBRT involves the precise delivery of
      highly conformal and image-guided external beam radiotherapy with high doses per
      fraction. It is increasingly being applied in management of spinal tumours.
      Thirty-six courses of spine SBRT in 34 patients were delivered between May 2010
      and December 2013. Mean patient age was 58 years. Treatment was predominantly for
      metastatic disease, applied in de novo (n=22), retreatment (n=14) and
      postoperative (n=8) settings. Prescribed doses included 18-30 Gy in 1-5
      fractions. SBRT technique evolved during the study period, resulting in a
      relative dose escalation. No severe acute toxicities were observed. At median
      follow-up of 7.4 months (range: 1.7-22.2), no late radiation myelopathy was
      observed. Risk of new/worsening vertebral compression fractures was 22% (n=8) and
      was significantly associated with increasing Spinal Instability Neoplastic Scores
      (p=0.0002). In-field control was 86% with relapse occurring at a median interval
      of 2.8 months (range: 1.9-4.7). Thirteen patients (36%) died and median overall
      survival has not been reached. SBRT is an evolving technology with promising
      early efficacy and safety results. The outcomes of this series are comparable
      with international literature, and await longer follow-up.

PMID- 25979255
TI  - Clinicopathological correlates of extrasellar growth patterns in pituitary
      adenomas.
AB  - We reviewed clinical, imaging and histopathology details of 297 patients who
      underwent surgery for pituitary adenomas, with an equal distribution of
      functional and non-functioning tumors, to examine clinicopathological correlates
      of extrasellar growth. Knosp grades of 3 and 4 on MRI defined cavernous sinus
      invasion, Hardy grades of C and D defined significant suprasellar/subfrontal
      extension, and intraoperative evidence of tumor eroding through the clivus or
      sellar floor defined infrasellar invasion. Disease status at follow-up was known
      in 246 patients overall, including 35 patients who were evaluated for progression
      of residual disease on serial imaging. On univariate analysis, we found several
      statistically significant associations (p < 0.05) including adenoma size with
      age, sex and tumor protein p53 reactivity; cavernous sinus invasion with size,
      non-functional status, increased mitotic activity, an elevated MIB-1
      proliferation index and p53 reactivity; suprasellar/subfrontal extension with p53
      reactivity; and infrasellar invasion with age and tumor size. When adjusting for
      confounders with logistic regression, several significant associations were
      evident including adenoma size with male sex and p53 reactivity; cavernous sinus
      invasion with size and elevated MIB-1 proliferation index; suprasellar/subfrontal
      extension with p53 reactivity; and infrasellar invasion with adenoma size alone.
      Patients with early progression of postoperative residual tumor were younger with
      a non-significant trend towards higher MIB-1 proliferation indices. Individual
      patterns of extrasellar growth in pituitary adenomas are associated with unique
      clinical and immunohistochemical profiles. Younger patients with elevated MIB-1
      values are probably at high risk for early recurrence of non-functioning tumors.
      Definitions of atypia must be standardized before more robust assumptions about
      tumor biology can be established.

PMID- 25979257
TI  - The Information and Motivation and Behavioral Skills Model of ART Adherence among
      HIV-Positive Adults in Mexico.
AB  - INTRODUCTION: Middle-income countries are in need of research that uses
      theoretical-based models to assess factors that predict adherence to
      antiretroviral therapy (ART) and help in the design, implementation, and
      evaluation of interventions for nonadherent populations. In Mexico, the
      Information and Motivation and Behavioral Skills (IMB) Model of ART Adherence
      constructs is useful in describing and predicting adherence behaviors in various
      samples but has not been articulated to people living with HIV (PLWH) on ART. The
      aim of this was to characterize the IMB core constructs and identify correlates
      of ART adherence in an HIV-positive clinic sample in Mexico. METHODS: A
      convenience sample of 109 HIV-positive patients attending their monthly visits at
      a local public hospital were interviewed with the Spanish version of the
      LifeWindows IMB ART Adherence Questionnaire (LW-IMB-AAQ) as well as a
      sociodemographic questionnaire. All participants were recruited from a hospital
      based outpatient clinical care site. RESULTS: Partial confirmation of the
      relationships proposed by the IMB Model of ART Adherence was found. As predicted
      by the model, only behavioral skills had direct association with all measures of
      self-reported adherence, and motivation was associated with behavioral skills.
      Information did not demonstrate significant relations to either motivation or
      behavioral skills, nor did it directly associate with adherence. Self-reported
      adherence did not associate with CD4 counts, nor did any of the IMB model core
      constructs. CONCLUSION: Applicability of the IMB Model of ART Adherence in this
      setting is discussed. The IMB Model of ART Adherence offered promise in this
      population and could help tailor population-specific interventions to promote
      high rates of ART adherence.

PMID- 25979256
TI  - Functional gait outcomes for idiopathic normal pressure hydrocephalus after
      primary endoscopic third ventriculostomy.
AB  - We evaluated if patients with idiopathic normal pressure hydrocephalus (iNPH)
      showed functional improvement after primary endoscopic third ventriculostomy
      (ETV). The efficacy of ETV for iNPH remains controversial. We retrospectively
      reviewed 10 consecutive patients treated between 2009 and 2011 with ETV for iNPH.
      Seven patients with a median age of 73 years (range: 60-80) who underwent a
      primary ETV for iNPH were included for analysis. Median follow-up was 39 months
      (range: 26-46). Post-ETV stoma and aqueductal and cisternal flows were confirmed
      via high resolution, gradient echo and phase contrast MRI. Post-ETV timed up and
      go (TUG) and Tinetti performance oriented mobility assessment scores were
      compared to pre- and post-lumbar puncture (LP) values. A second LP was performed
      if ETV failed to sustain the observed improvement after initial LP. Patients who
      demonstrated ETV failure were subsequently shunted. Compared to pre-LP TUG and
      Tinetti values of 14.00 seconds (range: 12.00-23.00) and 22 (range: 16-24), post
      LP scores improved to 11.00 seconds (range: 8.64-15.00; p=0.06) and 25 (range: 24
      28; p=0.02), respectively. ETV failed to sustain this improvement with slight
      worsening between pre-LP and post-ETV TUG and Tinetti scores. Improvement from
      pre-LP assessment was regained after shunting and at last follow-up with TUG and
      Tinetti scores of 12.97 seconds (range: 9.00-18.00; p=0.250) and 25 (range: 18
      27; p=0.07), and 11.87 seconds (range: 8.27-18.50; p=0.152) and 23 (range: 18-26;
      p=0.382), respectively. Despite stoma patency, ETV failed to sustain functional
      improvement seen after LP, however, improvement was regained after subsequent
      shunting suggesting that shunt placement remains the preferred treatment for
      iNPH.

PMID- 25979258
TI  - Reducing False-Positive HIV Diagnosis in Niger: A Women's Issue.
AB  - The entry into both HIV care and secondary prevention is first through the
      knowledge of one's own HIV status. Testing for HIV remains challenging in
      countries where clinicians rely on rapid testing algorithms because the routine
      use of confirmatory Western blot technology is unavailable. In this case report,
      we describe the case of a pregnant woman in Niger, who was falsely labeled as HIV
      positive during prenatal visits. We also describe our clinical algorithm that was
      developed to facilitate retesting in patients who initially tested HIV positive
      or indeterminant with rapid diagnostic tests. Vigilance is necessary to ensure
      that appropriate identification and treatment of HIV is provided to reduce mother
      to-child transmission of HIV, to appropriately allocate resources, and to avoid
      falsely labeling patients with HIV. 

PMID- 25979259
TI  - Investigation of Host-Gut Microbiota Modulation of Therapeutic Outcome.
AB  - A broader understanding of factors underlying interindividual variation in
      pharmacotherapy is important for our pursuit of "personalized medicine." Based on
      knowledge gleaned from the investigation of human genetics, drug-metabolizing
      enzymes, and transporters, clinicians and pharmacists are able to tailor
      pharmacotherapies according to the genotype of patients. However, human host
      factors only form part of the equation that accounts for heterogeneity in
      therapeutic outcome. Notably, the gut microbiota possesses wide-ranging metabolic
      activities that expand the metabolic functions of the human host beyond that
      encoded by the human genome. In this review, we first illustrate the mechanisms
      in which gut microbes modulate pharmacokinetics and therapeutic outcome. Second,
      we discuss the application of metabonomics in deciphering the complex host-gut
      microbiota interaction in pharmacotherapy. Third, we highlight an integrative
      approach with particular mention of the investigation of gut microbiota using
      culture-based and culture-independent techniques to complement the investigation
      of the host-gut microbiota axes in pharmaceutical research.

PMID- 25979260
TI  - Characterization of Species Differences in Tissue Diltiazem Deacetylation
      Identifies Ces2a as a Rat-Specific Diltiazem Deacetylase.
AB  - Diltiazem, a calcium channel blocker, is mainly metabolized via demethylation or
      deacetylation in humans. Diltiazem demethylation is catalyzed by cytochrome P450
      2D6 and 3A4. Although it was previously reported that the area under the curve
      ratio of deacetyldiltiazem to diltiazem after oral dosing with diltiazem in rats
      was sevenfold higher than in humans, the molecular mechanisms underlying this
      species difference remain to be clarified. In the present study, we compared the
      diltiazem deacetylase activity in liver, intestinal, renal, and pulmonary
      microsome preparations of human and experimental animal tissues to identify the
      specific deacetylase enzyme(s) involved in deacetylation. Diltiazem deacetylase
      activity was detected in rat liver and small intestine microsome preparations,
      but not in those from human, monkey, dog, and mouse tissues. Further purification
      of rat liver microsome (RLM) proteins identified four carboxylesterase (Ces)
      enzymes (Ces1d, Ces1e, Ces1f, and Ces2a) as potential candidate deacetylases. On
      the basis of their tissue distribution, the Ces2a enzyme was considered to be the
      enzyme that was responsible for diltiazem deacetylation. Furthermore, recombinant
      rat Ces2a expressed in Sf21 cells displayed efficient diltiazem deacetylase
      activity with similar Km values as RLM. In addition, the inhibitory
      characteristics of various chemical inhibitors were similar between recombinant
      rat Ces2a and RLM. In conclusion, we determined that only rat tissues were able
      to catalyze diltiazem deacetylation. The characterization of Ces enzymes in
      animal species, as undertaken in this study, will prove useful to predict the
      species-specific pharmacokinetics differences between the in vivo models used for
      drug development. 

PMID- 25979261
TI  - Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.
AB  - We developed murine CYP3A knockout ko chimeric mice with humanized liver
      expressing human P450S similar to those in humans and whose livers and small
      intestines do not express murine CYP3A this: approach may overcome effects of
      residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with
      humanized liver, such as PXB-mice [urokinase plasminogen activator/severe
      combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human
      hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in
      humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host
      mice, human albumin levels logarithmically increased until approximately 60 days
      after transplantation, findings similar to those in PXB-mice. Quantitative real
      time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs,
      SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were
      also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA
      expression in mouse liver and intestine. Findings for midazolam and triazolam
      metabolic activities in liver microsomes were comparable between Cyp3a KO
      chimeric mice and PXB-mice. In contrast, these activities in the intestine of
      Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the
      knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a
      KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold
      upregulated compared with PXB-mice, respectively. However, human hepatocyte
      transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55
      level partly (still 13-fold upregulated) compared with those in PXB-mice.
      Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte
      transplantation in Cyp3a KO chimeric mice.

PMID- 25979262
TI  - Variability in Expression of CYP3A5 in Human Fetal Liver.
AB  - Members of the cytochrome P450 3A (CYP3A) subfamily of drug metabolizing enzymes
      exhibit developmental changes in expression in human liver characterized by a
      transition between CYP3A7 and CYP3A4 over the first few years of life. In
      contrast, the developmental expression of CYP3A5 is less well understood due to
      polymorphic expression of the enzyme in human tissues as a result of the
      prevalence of the CYP3A5*3 allele, which leads to alternative splicing. We
      further explored the expression of CYP3A5 and the impact of alternative splicing
      on the variability of CYP3A5 functional activity in a large bank of human
      prenatal liver samples (7 to 32 weeks of age postconception). The expression of
      normally spliced CYP3A5 mRNA in all human fetal liver samples varied 235-fold
      whereas CYP3A5 SV1 mRNA was only detected in fetal liver samples with at least
      one CYP3A5*3 allele. Formation of 1'-OH midazolam (MDZ) varied 79-fold, and the
      ratio of 1'-OH MDZ to 4-OH MDZ varied 8-fold and depended on the presence or
      absence of the CYP3A5*3 allele. Formation of 4-OH MDZ was significantly
      associated with 1'-OH MDZ (r(2) = 0.76, P < 0.0001) but varied (36-fold)
      independently of CYP3A5 genotype or expression. The substantial interindividual
      variability that remains even after stratification for CYP3A5 genotype suggests
      that factors such as environmental exposure and epigenetic alterations act in
      addition to genetic variation to contribute to the variability of CYP3A5
      expression in human prenatal liver. 

PMID- 25979263
TI  - De novo design of heat-repressible RNA thermosensors in E. coli.
AB  - RNA-based temperature sensing is common in bacteria that live in fluctuating
      environments. Most naturally-occurring RNA thermosensors are heat-inducible, have
      long sequences, and function by sequestering the ribosome binding site in a
      hairpin structure at lower temperatures. Here, we demonstrate the de novo design
      of short, heat-repressible RNA thermosensors. These thermosensors contain a
      cleavage site for RNase E, an enzyme native to Escherichia coli and many other
      organisms, in the 5' untranslated region of the target gene. At low temperatures,
      the cleavage site is sequestered in a stem-loop, and gene expression is
      unobstructed. At high temperatures, the stem-loop unfolds, allowing for mRNA
      degradation and turning off expression. We demonstrated that these thermosensors
      respond specifically to temperature and provided experimental support for the
      central role of RNase E in the mechanism. We also demonstrated the modularity of
      these RNA thermosensors by constructing a three-input composite circuit that
      utilizes transcriptional, post-transcriptional, and post-translational
      regulation. A thorough analysis of the 24 thermosensors allowed for the
      development of design guidelines for systematic construction of similar
      thermosensors in future applications. These short, modular RNA thermosensors can
      be applied to the construction of complex genetic circuits, facilitating rational
      reprogramming of cellular processes for synthetic biology applications. 

PMID- 25979264
TI  - SIFTER search: a web server for accurate phylogeny-based protein function
      prediction.
AB  - We are awash in proteins discovered through high-throughput sequencing projects.
      As only a minuscule fraction of these have been experimentally characterized,
      computational methods are widely used for automated annotation. Here, we
      introduce a user-friendly web interface for accurate protein function prediction
      using the SIFTER algorithm. SIFTER is a state-of-the-art sequence-based gene
      molecular function prediction algorithm that uses a statistical model of function
      evolution to incorporate annotations throughout the phylogenetic tree. Due to the
      resources needed by the SIFTER algorithm, running SIFTER locally is not trivial
      for most users, especially for large-scale problems. The SIFTER web server thus
      provides access to precomputed predictions on 16 863 537 proteins from 232 403
      species. Users can explore SIFTER predictions with queries for proteins, species,
      functions, and homologs of sequences not in the precomputed prediction set. The
      SIFTER web server is accessible at http://sifter.berkeley.edu/ and the source
      code can be downloaded. 

PMID- 25979265
TI  - CSI 3.0: a web server for identifying secondary and super-secondary structure in
      proteins using NMR chemical shifts.
AB  - The Chemical Shift Index or CSI 3.0 (http://csi3.wishartlab.com) is a web server
      designed to accurately identify the location of secondary and super-secondary
      structures in protein chains using only nuclear magnetic resonance (NMR) backbone
      chemical shifts and their corresponding protein sequence data. Unlike earlier
      versions of CSI, which only identified three types of secondary structure (helix,
      beta-strand and coil), CSI 3.0 now identifies total of 11 types of secondary and
      super-secondary structures, including helices, beta-strands, coil regions, five
      common beta-turns (type I, II, I', II' and VIII), beta hairpins as well as
      interior and edge beta-strands. CSI 3.0 accepts experimental NMR chemical shift
      data in multiple formats (NMR Star 2.1, NMR Star 3.1 and SHIFTY) and generates
      colorful CSI plots (bar graphs) and secondary/super-secondary structure
      assignments. The output can be readily used as constraints for structure
      determination and refinement or the images may be used for presentations and
      publications. CSI 3.0 uses a pipeline of several well-tested, previously
      published programs to identify the secondary and super-secondary structures in
      protein chains. Comparisons with secondary and super-secondary structure
      assignments made via standard coordinate analysis programs such as DSSP, STRIDE
      and VADAR on high-resolution protein structures solved by X-ray and NMR show >90%
      agreement between those made with CSI 3.0. 

PMID- 25979267
TI  - Tongue necrosis in giant-cell arteritis.

PMID- 25979266
TI  - Yeast high mobility group protein HMO1 stabilizes chromatin and is evicted during
      repair of DNA double strand breaks.
AB  - DNA is packaged into condensed chromatin fibers by association with histones and
      architectural proteins such as high mobility group (HMGB) proteins. However, this
      DNA packaging reduces accessibility of enzymes that act on DNA, such as proteins
      that process DNA after double strand breaks (DSBs). Chromatin remodeling
      overcomes this barrier. We show here that the Saccharomyces cerevisiae HMGB
      protein HMO1 stabilizes chromatin as evidenced by faster chromatin remodeling in
      its absence. HMO1 was evicted along with core histones during repair of DSBs, and
      chromatin remodeling events such as histone H2A phosphorylation and H3 eviction
      were faster in absence of HMO1. The facilitated chromatin remodeling in turn
      correlated with more efficient DNA resection and recruitment of repair proteins;
      for example, inward translocation of the DNA-end-binding protein Ku was faster in
      absence of HMO1. This chromatin stabilization requires the lysine-rich C-terminal
      extension of HMO1 as truncation of the HMO1 C-terminal tail phenocopies hmo1
      deletion. Since this is reminiscent of the need for the basic C-terminal domain
      of mammalian histone H1 in chromatin compaction, we speculate that HMO1 promotes
      chromatin stability by DNA bending and compaction imposed by its lysine-rich
      domain and that it must be evicted along with core histones for efficient DSB
      repair. 

PMID- 25979268
TI  - Neuroendocrine tumours of the small bowel: interpretation of raised circulating
      chromogranin A, urinary 5 hydroxy indole acetic acid and circulating neurokinin
      A.
AB  - BACKGROUND: Neuroendocrine tumours (NETs) of the small bowel are difficult to
      diagnose as symptoms are non-specific and more often found in common
      gastrointestinal diseases. Chromogranin A (CGA), urinary 5 hydroxy indole acetic
      acid (U-5HIAA) and Neurokinin A (NKA) are used as laboratory diagnostic tests but
      results may be misleading or confusing. AIM: To clarify the relevance of NET
      biomarkers for diagnosis of small bowel NETs. DESIGN: A review of laboratory test
      results. METHODS: We reviewed 500 consecutive raised plasma CGA, U-5HIAA and
      plasma NKA, results from patients in N Ireland. The diagnosis of NET was
      confirmed by the Northern Ireland Cancer Registry. RESULTS: In 500 specimens
      recording raised CGA, 52.2% were from patients with NETs, 13.6% being small bowel
      tumours, 5.4% of specimens from patients with auto-immune atrophic gastritis and
      15.4% from patients taking proton pump inhibitors. In 500 specimens with raised U
      5HIAA, 87.8% were from patients with NETs, 68.2% being small bowel tumours. Lung
      NETs contributed 12.2% and NETs from other sites, 7.4%. Of 500 specimens with
      raised NKA (reference range (RR) > 20 ng/L), 72.6% were from patients with small
      bowel NETs and 6% specimens from patients with other NETs. In 20% of specimens
      NKA concentrations were 21-23 ng/L, within limits of assay precision. CONCLUSION:
      CGA remains the best general circulating marker for NETs although only half of
      raised test results are due to an NET. U-5HIAA is an excellent marker for small
      bowel and lung NETs with 80% of high test results confirming these diagnoses. NKA
      is the most specific biomarker for small bowel NETs.

PMID- 25979269
TI  - A prospective study on the outcome of human immunodeficiency virus-infected
      patients requiring mechanical ventilation in a high-burden setting.
AB  - BACKGROUND: There is a paucity of data on the mortality of patients admitted to
      the intensive care unit (ICU), despite the fact that human immunodeficiency virus
      (HIV)-related diseases represent a significant burden to health care resources
      particularly in sub-Saharan Africa. AIM: To describe the outcome and prognostic
      factors of HIV-infected patients requiring mechanical ventilation in an ICU.
      DESIGN: Prospective observational study. METHODS: All 54 patients (34.8 +/- 10.4
      years, 38 females) admitted with confirmed HIV from October 2012 until May 2013
      were enrolled. Disease severity was graded according to APACHEII score. Admission
      diagnoses, clinical features and laboratory investigations, complications and
      outcomes were recorded. RESULTS: The mean length of ICU stay was 11.0 days
      (range: 1-49 days), and 33 patients survived (ICU mortality: 38.9%). The in
      hospital mortality at 30 days was 48.1%. ICU mortality was associated with an
      AIDS-defining diagnosis (OR = 7.97, P = 0.003). Non-survivors had higher APACHEII
      scores (25.8 vs. 18.6, P = 0.001) and lower mean admission CD4 counts (102.5 vs.
      225.2, P = 0.014). Multiple logistical regression analysis confirmed the
      independent predictive value of WHO stage 4 disease (P = 0.008), lower mean CD4
      count on admission (P = 0.057) and higher APACHEII score (P = 0.010) on ICU
      mortality, and WHO stage 4 (P = 0.007) and higher APACHE II score (P = 0.003) on
      30-day mortality. CONCLUSIONS: The ICU mortality of mechanically ventilated HIV
      positive patients was high. WHO stage 4 disease and a higher APACHEII score were
      predictive of both ICU and 30-day mortality, whereas a low CD4 count on admission
      was associated with ICU mortality.

PMID- 25979270
TI  - Prognostic significance of anaemia in patients with heart failure with preserved
      and reduced ejection fraction: results from the MAGGIC individual patient data
      meta-analysis.
AB  - BACKGROUND: Anaemia is common among patients with heart failure (HF) and is an
      important prognostic marker. AIM: We sought to determine the prognostic
      importance of anaemia in a large multinational pooled dataset of prospectively
      enrolled HF patients, with the specific aim to determine the prognostic role of
      anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF,
      respectively). DESIGN: Individual person data meta-analysis. METHODS: Patients
      with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined
      as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF >= 50%; HF
      REF was EF < 50%. Cox proportional hazard modelling, with adjustment for
      clinically relevant variables, was undertaken to investigate factors associated
      with 3-year all-cause mortality. RESULTS: Thirteen thousand two hundred and
      ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF
      PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF
      (42.8 and 41.6% respectively). Compared with patients with normal Hb values,
      those with anaemia were older, were more likely to have diabetes, ischaemic
      aetiology, New York Heart Association class IV symptoms, lower estimated
      glomerular filtration rate and were more likely to be taking diuretic and less
      likely to be taking a beta-blocker. Patients with anaemia had higher all-cause
      mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25
      1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13
      2.90) in HF-REF. CONCLUSIONS: Anaemia is an adverse prognostic factor in HF
      irrespective of EF. The prognostic importance of anaemia was greatest in patients
      with HF-REF.

PMID- 25979271
TI  - Neutrophil-to-lymphocyte ratio: A novel and simple prognostic marker for
      infective endocarditis.
AB  - Infective endocarditis is a life-threatining infectious disease characterized by
      high morbidity and mortality. Leukocytes play a main role in infectious diseases.
      Neutrophils and lymphocytes are subgroup of leukocytes, and they are routinely
      measured as a part of automated complete blood count test. The neutrophil-to
      lymphocyte ratio is an independent predictor of unfavorable clinical outcomes in
      infectious and cardiovascular diseases. 

PMID- 25979272
TI  - Associations of fluid overload with mortality and kidney recovery in patients
      with acute kidney injury: A systematic review and meta-analysis.
AB  - PURPOSE: Fluid resuscitation is commonly administered to maintain adequate renal
      perfusion in critically ill patients to prevent or even treat acute kidney injury
      (AKI). However, recent studies show that fluid overload is common and might be
      associated with poor outcomes in patients with AKI. Hence, the objective of this
      study was to assess the associations of fluid overload with mortality and kidney
      recovery in patients with AKI. MATERIALS AND METHODS: We electronically searched
      original articles published in peer-reviewed journals from their inception to
      January 2015 in PubMed, EMBASE, the Cochrane Library databases, Google Scholar,
      and Chinese database (SinoMed). We additionally searched the reference lists of
      all retrieved articles. We performed a systematic review and meta-analysis of all
      eligible cohort or case-control studies of fluid overload in patients with AKI.
      The primary outcomes were mortality and kidney recovery. We pooled adjusted odds
      ratios (ORs) with 95% confidence intervals (95% CIs) by using Review Manager 5.2
      (The Cochrane Collaboration, Oxford, UK). RESULTS: A total of 5095 patients from
      12 cohort studies published from 2008 to 2014 were included. A significant
      positive association was found between fluid overload and mortality in patients
      with AKI (OR, 2.23; 95% CI, 1.66-3.01), with similar findings in sepsis (OR,
      2.27; 95% CI, 1.69-to 3.03) and nonsepsis subgroups (OR, 3.40; 95% CI, 2.50
      4.63). There was also a significant association between mean fluid balance
      (continuous variables) and mortality (OR, 1.16; 95% CI, 1.07-1.27). Although
      there was a trend of lower rate of kidney recovery in the fluid overload group,
      there was no significant association between fluid overload and kidney recovery
      (OR, 0.66; 95% CI, 0.37-1.15), or dialysis dependence (OR, 0.72; 95% CI, 0.38
      1.35). CONCLUSIONS: Fluid overload is associated with an increased risk of
      mortality in patients with AKI. The evidence of the relationship between fluid
      overload and kidney recovery is insufficient.

PMID- 25979273
TI  - High prevalence of cross-resistance to fluoroquinolone and cotrimoxazole in
      tetracycline-resistant Escherichia coli human clinical isolates.

PMID- 25979274
TI  - Effect of post-voiding urine volume on progression of renal function decline in
      patients with type 2 diabetes.
AB  - Diabetic bladder dysfunction (DBD) is a common complication of type 2 diabetes
      mellitus (T2DM). The association between DBD and progression of diabetic
      nephropathy has not been clarified. In this study, we investigated the
      relationship between post-voiding residual urine (PVR) with decline in renal
      function in patients with type 2 diabetes. This retrospective study included 164
      patients at a single center. We collected medical histories and laboratory
      findings of patients undergoing uroflowmetry from January 1, 2008 to October 30,
      2013. Renal function was assessed by calculating the estimated glomerular
      filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD)
      study equation. We evaluated whether greater PVR was a risk factor for faster
      decline of GFR during a 1-year follow-up. The subjects' mean age was 65+/-12
      years, duration of diabetes 12.8+/-8.8 years, baseline serum creatinine level
      106.1+/-53.0 MUmol/L, and eGFR was 64.6+/-25.2 mL/min/1.73 m(2). Mean PVR was
      69.8+/-96.3 mL and in 17.7% of subjects, PVR>100 mL. In linear regression
      analysis, PVR was independently associated with GFR decrease (standardized beta
      coefficient=0.2, P=0.009). Multiple logistic analysis showed that subjects with
      PVR>100 mL had a 2.8-fold higher risk of an eGFR change during 1 year higher than
      the median value of all subjects (95% confidence interval, 1.1-6.8; P=0.03).
      Increased PVR was independently associated with a more rapid decline in renal
      function in patients with type 2 diabetes.

PMID- 25979275
TI  - Proceedings of the 5th International DAWN Summit 2014: Acting together to make
      person-centred diabetes care a reality.
AB  - Almost 250 stakeholders from across the world, representing all aspects of
      diabetes, attended the 5th International DAWN Summit. The summit focussed on the
      issues raised by the recently published DAWN2 study, placing particular emphasis
      on promoting the concept of person-centred diabetes care. Discussions between the
      delegates took place throughout a variety of sessions, with presentations,
      interactive exchanges and workshops providing a platform for clarification of
      common global priorities and opportunities for joint action. Following the
      summit, these ideas were developed further, leading to the creation of a Global
      Action Framework. The framework aims to support the ongoing local implementation
      of change in response to the DAWN2 results, while helping enable person-centred
      diabetes care to become a reality at all levels. 

PMID- 25979277
TI  - Optimal prophylactic vaccination in segregated populations: When can we improve
      on the equalising strategy?
AB  - One of the fundamental problems in public health is how to allocate a limited set
      of resources to have the greatest benefit on the health of the population. This
      often leads to difficult value judgements about budget allocations. However, one
      scenario that is directly amenable to mathematical analysis is the optimal
      allocation of a finite stockpile of vaccine when the population is partitioned
      into many relatively small cliques, often conceptualised as households. For the
      case of SIR (susceptible-infectious-recovered) dynamics, analysis and numerics
      have supported the conjecture that an equalising strategy (which leaves equal
      numbers of susceptible individuals in each household) is optimal under certain
      conditions. However, there exists evidence that some of these conditions may be
      invalid or unsuitable in many situations. Here we consider how well the
      equalising strategy performs in a range of other scenarios that deviate from the
      idealised household model. We find that in general the equalising strategy often
      performs optimally, even far from the idealised case. However, when considering
      large subpopulation sizes, frequency-dependent transmission and intermediate
      levels of vaccination, optimality is often achieved through more heterogeneous
      vaccination strategies. 

PMID- 25979276
TI  - Exposure to low doses of Coxiella burnetii caused high illness attack rates:
      Insights from combining human challenge and outbreak data.
AB  - BACKGROUND: As a major zoonotic pathogen, characterization of the infectivity and
      pathogenicity of Coxiella burnetii is essential to understand Q-fever
      epidemiology. OBJECTIVES: We want to extend a recently published human dose
      response model based on experimental challenge of young adult males to include
      other age groups and both genders. Additionally, we can estimate the spatial
      distribution of exposure based on observed outbreak data. METHODS: Dose response
      assessment based on human challenge, is extended by including outbreak data,
      using location of cases as a proxy for exposure. This allows estimation of the
      influence of age and gender on the probability of developing symptoms of acute
      respiratory illness. RESULTS: In an outbreak in Switzerland, in 1983, exposure to
      C. burnetii was shown to depend strongly on distance from the source. The
      susceptibility of males to develop Q-fever decreases with age, while in females,
      middle-aged women appear to have the lowest risk. CONCLUSIONS: The published dose
      response model for Q-fever, based on experimental challenge of a small group of
      human volunteers, has been updated with data from a well studied outbreak.
      Infectivity estimates remain high, and even low doses (of 10 or fewer organisms)
      cause a high risk of illness.

PMID- 25979279
TI  - Pneumococcal vaccination in older adults in the era of childhood vaccination:
      Public health insights from a Norwegian statistical prediction study.
AB  - Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13
      valent conjugate vaccine (PCV13), are available for prevention of invasive
      pneumococcal disease (IPD) in the population aged 65 years and older (65+). The
      IPD epidemiology in the 65+ is undergoing change due to indirect effects of
      childhood immunisation. Vaccine recommendations for the 65+ must take into
      account these trends in epidemiology. We therefore explored the preventive
      potential of vaccination strategies to prevent IPD in the 65+, including PPV23,
      PCV13 or PCV13 + PPV23 in 2014-2019. Quasi-Poisson regression models were fitted
      to 2004-2014 population-wide surveillance data and used to predict incidences for
      vaccine-type and non-vaccine type IPD. We determined the number of people needed
      to be vaccinated to prevent one case per season (NNV) for each strategy and
      estimated the public health impact on the IPD case counts from increasing the
      vaccine uptake to 28-45%. Our results indicate that PCV13-IPD will decrease by
      71% from 58 (95% prediction interval 55-61) cases in 2014/15 to 17 (6-52) in
      2018/19 and PPV23-IPD by 32% from 168 (162-175) to 115 (49-313) cases. The NNV
      will increase over time for all strategies because of a decreasing vaccine-type
      IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23
      NNV. Increasing the vaccine uptake will lead to a larger public health impact for
      all scenarios. Combining PCV13 and PPV23 is most effective, but the additional
      effect of PCV13 will decrease and is only marginal in 2018/19. Our study
      demonstrates the importance of increasing PPV23 uptake and of developing vaccines
      that confer broader immunity.

PMID- 25979278
TI  - The social contact hypothesis under the assumption of endemic equilibrium:
      Elucidating the transmission potential of VZV in Europe.
AB  - The basic reproduction number R0 and the effective reproduction number R are
      pivotal parameters in infectious disease epidemiology, quantifying the
      transmission potential of an infection in a population. We estimate both
      parameters from 13 pre-vaccination serological data sets on varicella zoster
      virus (VZV) in 12 European countries and from population-based social contact
      surveys under the commonly made assumptions of endemic and demographic
      equilibrium. The fit to the serology is evaluated using the inferred effective
      reproduction number R as a model eligibility criterion combined with AIC as a
      model selection criterion. For only 2 out of 12 countries, the common choice of a
      constant proportionality factor is sufficient to provide a good fit to the
      seroprevalence data. For the other countries, an age-specific proportionality
      factor provides a better fit, assuming physical contacts lasting longer than 15
      min are a good proxy for potential varicella transmission events. In all
      countries, primary infection with VZV most often occurs in early childhood, but
      there is substantial variation in transmission potential with R0 ranging from 2.8
      in England and Wales to 7.6 in The Netherlands. Two non-parametric methods, the
      maximal information coefficient (MIC) and a random forest approach, are used to
      explain these differences in R0 in terms of relevant country-specific
      characteristics. Our results suggest an association with three general factors:
      inequality in wealth, infant vaccination coverage and child care attendance. This
      illustrates the need to consider fundamental differences between European
      countries when formulating and parameterizing infectious disease models.

PMID- 25979281
TI  - Unknown age in health disorders: A method to account for its cumulative effect
      and an application to feline viruses interactions.
AB  - Parasite interactions have been widely evidenced experimentally but field studies
      remain rare. Such studies are essential to detect interactions of interest and
      access (co)infection probabilities but face methodological obstacles. Confounding
      factors can create statistical associations, i.e. false parasite interactions.
      Among them, host age is a crucial covariate. It influences host exposition and
      susceptibility to many infections, and has a mechanical effect, older individuals
      being more at risk because of a longer exposure time. However, age is difficult
      to estimate in natural populations. Hence, one should be able to deal at least
      with its cumulative effect. Using a SI type dynamic model, we showed that the
      cumulative effect of age can generate false interactions theoretically
      (deterministic modeling) and with a real dataset of feline viruses (stochastic
      modeling). The risk to wrongly conclude to an association was maximal when
      parasites induced long-lasting antibodies and had similar forces of infection. We
      then proposed a method to correct for this effect (and for other potentially
      confounding shared risk factors) and made it available in a new R package,
      Interatrix. We also applied the correction to the feline viruses. It offers a way
      to account for an often neglected confounding factor and should help identifying
      parasite interactions in the field, a necessary step towards a better
      understanding of their mechanisms and consequences. 

PMID- 25979280
TI  - Impact of coverage-dependent marginal costs on optimal HPV vaccination
      strategies.
AB  - The effectiveness of vaccinating males against the human papillomavirus (HPV)
      remains a controversial subject. Many existing studies conclude that increasing
      female coverage is more effective than diverting resources into male vaccination.
      Recently, several empirical studies on HPV immunization have been published,
      providing evidence of the fact that marginal vaccination costs increase with
      coverage. In this study, we use a stochastic agent-based modeling framework to
      revisit the male vaccination debate in light of these new findings. Within this
      framework, we assess the impact of coverage-dependent marginal costs of vaccine
      distribution on optimal immunization strategies against HPV. Focusing on the two
      scenarios of ongoing and new vaccination programs, we analyze different resource
      allocation policies and their effects on overall disease burden. Our results
      suggest that if the costs associated with vaccinating males are relatively close
      to those associated with vaccinating females, then coverage-dependent, increasing
      marginal costs may favor vaccination strategies that entail immunization of both
      genders. In particular, this study emphasizes the necessity for further empirical
      research on the nature of coverage-dependent vaccination costs. 

PMID- 25979283
TI  - Epidemiological modelling for the assessment of bovine tuberculosis surveillance
      in the dairy farm network in Emilia-Romagna (Italy).
AB  - Assessing the performance of a surveillance system for infectious diseases of
      domestic animals is a challenging task for health authorities. Therefore, it is
      important to assess what strategy is the most effective in identifying the onset
      of an epidemic and in minimizing the number of infected farms. The aim of the
      present work was to evaluate the performance of the bovine tuberculosis (bTB)
      surveillance system in the network of dairy farms in the Emilia-Romagna (ER)
      Region, Italy. A bTB-free Region since 2007, ER implements an integrated
      surveillance strategy based on three components, namely routine on-farm
      tuberculin skin-testing performed every 3 years, tuberculin skin-testing of
      cattle exchanged between farms, and post-mortem inspection at slaughterhouses. We
      assessed the effectiveness of surveillance by means of a stochastic network model
      of both within-farm and between-farm bTB dynamics calibrated on data available
      for ER dairy farms. Epidemic dynamics were simulated for five scenarios: the
      current ER surveillance system, a no surveillance scenario that we used as the
      benchmark to characterize epidemic dynamics, three additional scenarios in which
      one of the surveillance components was removed at a time so as to outline its
      significance in detecting the infection. For each scenario we ran Monte Carlo
      simulations of bTB epidemics following the random introduction of an infected
      individual in the network. System performances were assessed through the
      comparative analysis of a number of statistics, including the time required for
      epidemic detection and the total number of infected farms during the epidemic.
      Our analysis showed that slaughterhouse inspection is the most effective
      surveillance component in reducing the time for disease detection, while routine
      surveillance in reducing the number of multi-farms epidemics. On the other hand,
      testing exchanged cattle improved the performance of the surveillance system only
      marginally. 

PMID- 25979282
TI  - The racial disparities in STI in the U.S.: Concurrency, STI prevalence, and
      heterogeneity in partner selection.
AB  - BACKGROUND: There is a large and persistent racial disparity in STI in the U.S.
      which has placed non-Hispanic-Blacks at disproportionately high risk. We tested a
      hypothesis that both individual-level risk factors (partner number, anal sex,
      condom use) and local-network features (concurrency and assortative mixing by
      race) combine to account for the association between race and chlamydia status.
      METHODS: Data from the Longitudinal Survey of Adolescent Health Wave III were
      used. Chlamydia status was determined using biomarkers. Individual-level risk
      behaviors were self-reported. Network location variables for concurrency and
      assortative mixing were imputed using egocentrically sample data on sexual
      partnerships. RESULTS: After controlling for demographic attributes including
      age, sex, marital status, education and health care access there remained a
      strong association between race and chlamydia status (OR = 5.23, 95% CI [3.83
      7.15], p < .001 for Non-Hispanic Blacks with Non-Hispanic Whites as the reference
      category). The inclusion of individual-level risk factors did not alter the
      association between race and chlamydia (OR = 5.23 for Non-Hispanic Blacks). The
      inclusion of concurrency and assortative mixing by race substantially reduced the
      association between race and chlamydia status (OR = 1.87, 95% CI [0.89-3.91] p >
      .05 for Non-Hispanic Blacks).

PMID- 25979284
TI  - Social deprivation and burden of influenza: Testing hypotheses and gaining
      insights from a simulation model for the spread of influenza.
AB  - Factors associated with the burden of influenza among vulnerable populations have
      mainly been identified using statistical methodologies. Complex simulation models
      provide mechanistic explanations, in terms of spatial heterogeneity and contact
      rates, while controlling other factors and may be used to better understand
      statistical patterns and, ultimately, design optimal population-level
      interventions. We extended a sophisticated simulation model, which was applied to
      forecast epidemics and validated for predictive ability, to identify mechanisms
      for the empirical relationship between social deprivation and the burden of
      influenza. Our modeled scenarios and associated epidemic metrics systematically
      assessed whether neighborhood composition and/or spatial arrangement could
      qualitatively replicate this empirical relationship. We further used the model to
      determine consequences of local-scale heterogeneities on larger scale disease
      spread. Our findings indicated that both neighborhood composition and spatial
      arrangement were critical to qualitatively match the empirical relationship of
      interest. Also, when social deprivation was fully included in the model, we
      observed lower age-based attack rates and greater delay in epidemic peak week in
      the most socially deprived neighborhoods. Insights from simulation models
      complement current understandings from statistical-based association studies.
      Additional insights from our study are: (1) heterogeneous spatial arrangement of
      neighborhoods is a necessary condition for simulating observed disparities in the
      burden of influenza and (2) unmeasured factors may lead to a better quantitative
      match between simulated and observed rate ratio in the burden of influenza
      between the most and least socially deprived populations. 

PMID- 25979285
TI  - Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control.
AB  - International air travel has already spread Ebola virus disease (EVD) to major
      cities as part of the unprecedented epidemic that started in Guinea in December
      2013. An infected airline passenger arrived in Nigeria on July 20, 2014 and
      caused an outbreak in Lagos and then Port Harcourt. After a total of 20 reported
      cases, including 8 deaths, Nigeria was declared EVD free on October 20, 2014. We
      quantified the impact of early control measures in preventing further spread of
      EVD in Nigeria and calculated the risk that a single undetected case will cause a
      new outbreak. We fitted an EVD transmission model to data from the outbreak in
      Nigeria and estimated the reproduction number of the index case at 9.0 (95%
      confidence interval [CI]: 5.2-15.6). We also found that the net reproduction
      number fell below unity 15 days (95% CI: 11-21 days) after the arrival of the
      index case. Hence, our study illustrates the time window for successful
      containment of EVD outbreaks caused by infected air travelers. 

PMID- 25979286
TI  - The distribution of the prevalence of ocular chlamydial infection in communities
      where trachoma is disappearing.
AB  - Mathematical models predict that the prevalence of infection in different
      communities where an infectious disease is disappearing should approach a
      geometric distribution. Trachoma programs offer an opportunity to test this
      hypothesis, as the World Health Organization (WHO) has targeted trachoma to be
      eliminated as a public health concern by the year 2020. We assess the
      distribution of the community prevalence of childhood ocular chlamydia infection
      from periodic, cross-sectional surveys in two areas of Ethiopia. These surveys
      were taken in a controlled setting, where infection was documented to be
      disappearing over time. For both sets of surveys, the geometric distribution had
      the most parsimonious fit of the distributions tested, and goodness-of-fit
      testing was consistent with the prevalence of each community being drawn from a
      geometric distribution. When infection is disappearing, the single sufficient
      parameter describing a geometric distribution captures much of the distributional
      information found from examining every community. The relatively heavy tail of
      the geometric suggests that the presence of an occasional high-prevalence
      community is to be expected, and does not necessarily reflect a transmission hot
      spot or program failure. A single cross-sectional survey can reveal which
      direction a program is heading. A geometric distribution of the prevalence of
      infection across communities may be an encouraging sign, consistent with a
      disease on its way to eradication. 

PMID- 25979287
TI  - Dengue disease outbreak definitions are implicitly variable.
AB  - Infectious diseases rarely exhibit simple dynamics. Outbreaks (defined as excess
      cases beyond response capabilities) have the potential to cause a
      disproportionately high burden due to overwhelming health care systems. The
      recommendations of international policy guidelines and research agendas are based
      on a perceived standardised definition of an outbreak characterised by a
      prolonged, high-caseload, extra-seasonal surge. In this analysis we apply
      multiple candidate outbreak definitions to reported dengue case data from Brazil
      to test this assumption. The methods identify highly heterogeneous outbreak
      characteristics in terms of frequency, duration and case burden. All definitions
      identify outbreaks with characteristics that vary over time and space. Further,
      definitions differ in their timeliness of outbreak onset, and thus may be more or
      less suitable for early intervention. This raises concerns about the application
      of current outbreak guidelines for early warning/identification systems. It is
      clear that quantitatively defining the characteristics of an outbreak is an
      essential prerequisite for effective reactive response. More work is needed so
      that definitions of disease outbreaks can take into account the baseline
      capacities of treatment, surveillance and control. This is essential if outbreak
      guidelines are to be effective and generalisable across a range of
      epidemiologically different settings. 

PMID- 25979288
TI  - Optimization of culture conditions for flexirubin production by Chryseobacterium
      artocarpi CECT 8497 using response surface methodology.
AB  - Flexirubins are the unique type of bacterial pigments produced by the bacteria
      from the genus Chryseobacterium, which are used in the treatment of chronic skin
      disease, eczema etc. and may serve as a chemotaxonomic marker. Chryseobacterium
      artocarpi CECT 8497, an yellowish-orange pigment producing strain was
      investigated for maximum production of pigment by optimizing medium composition
      employing response surface methodology (RSM). Culture conditions affecting
      pigment production were optimized statistically in shake flask experiments.
      Lactose, l-tryptophan and KH2PO4 were the most significant variables affecting
      pigment production. Box Behnken design (BBD) and RSM analysis were adopted to
      investigate the interactions between variables and determine the optimal values
      for maximum pigment production. Evaluation of the experimental results signified
      that the optimum conditions for maximum production of pigment (521.64 mg/L) in 50
      L bioreactor were lactose 11.25 g/L, l-tryptophan 6 g/L and KH2PO4 650 ppm.
      Production under optimized conditions increased to 7.23 fold comparing to its
      production prior to optimization. Results of this study showed that statistical
      optimization of medium composition and their interaction effects enable short
      listing of the significant factors influencing maximum pigment production from
      Chryseobacterium artocarpi CECT 8497. In addition, this is the first report
      optimizing the process parameters for flexirubin type pigment production from
      Chryseobacterium artocarpi CECT 8497. 

PMID- 25979289
TI  - A compound C-terminal nuclear localization signal of human SA2 stromalin.
AB  - Stromalins are evolutionarily conserved multifunctional proteins with the best
      known function in sister chromatid cohesion. Human SA2 stromalin, likely involved
      in the establishment of cohesion, contains numerous potential nuclear
      localization (NLS) and nuclear export signals (NES). Previously we have found
      that the C-terminus of SA2 contains NLS(s) functional in human cells. However,
      the identity of this signal remained unclear since three NLS-like sequences are
      present in that region. Here we analyzed the functionality of these putative
      signals by expressing GFP-tagged C-terminal part of SA2 or its fragments in a
      human cell line and in the yeast Saccharomyces cerevisiae. We found that in human
      cells the nuclear import is dependent on a unique compound di- or tripartite
      signal containing unusually long linkers between clusters of basic amino acids.
      Upon expression of the same SA2 fragment in yeast this signal is also functional
      and can be easily studied in more detail. 

PMID- 25979290
TI  - Stabilization of Fifth Digit Derotation Arthroplasty With an Absorbable Fixation
      Pin.
AB  - Derotation arthroplasty is the time-tested procedure for the repair of a
      symptomatic adductovarus deformity of the fifth toe. However, the procedure can
      result in an unstable floppy toe. A technique is described to stabilize this
      arthroplasty using an absorbable poly-L-lactic acid pin.

PMID- 25979291
TI  - A Solitary Fibrous Tumor (Cellular Form) of the Ankle.
AB  - A solitary fibrous tumor (SFT) is a rare type of mesenchymal tumor composed of
      uniform spindle cells that is classically described as a patternless feature. SFT
      normally originates from the pleura, with an SFT originating from skin rarely
      reported. We report what we believe to be the first case of an SFT arising from
      the ankle. Our case was confirmed histopathologically with immunohistochemical
      staining. 

PMID- 25979292
TI  - Concurrent Lateral Dorsal Cutaneous and Deep Peroneal Intraneural Ganglion Cysts
      in the Foot.
AB  - Intraneural ganglion cysts are non-neoplastic collections of mucinous material
      within the epineurium of peripheral nerves. We present a rare case of 2
      intraneural ganglion cysts in separate nerves of the foot, originating from
      different joints within the same joint complex. Our findings add to the large
      body of evidence supporting the unifying articular (synovial) theory. We
      emphasize the importance of delineating the cyst morphology and origins using
      high-resolution magnetic resonance imaging before surgery and searching for and
      resecting the articular branch or branches during surgery. 

PMID- 25979294
TI  - Tenosynovial Osteochondromatosis of the Flexor Hallucis Longus Tendon Treated by
      Tendoscopy.
AB  - Tendosynovial chondromatosis of the foot and ankle is a rare disease entity. We
      reported 3 patients with tenosynovial osteochondromatosis of flexor hallucis
      longus. They were successfully treated by arthroscopic synovectomy and removal of
      the loose bodies. 

PMID- 25979293
TI  - Correction of a Forefoot Deformity Caused by a Large, Solitary Metatarsal
      Osteochondroma in an Adolescent: A Case Report.
AB  - Solitary osteochondroma is the most common bone tumor, accounting for 20% to 50%
      of all benign bony tumors. Osteochondromas are usually found on the metaphysis of
      the long bones near the physis; the bones of the foot are less commonly involved.
      We describe a 13-year-old female with a large osteochondroma arising from the
      fourth metatarsal. Pressure from the tumor on the adjacent metatarsals had
      deformed her forefoot, creating cosmetic and functional problems. The second and
      third toes were deviated laterally at the metatarsophalangeal joint, and the
      fourth and fifth toes were deviated medially. In addition, the fourth and fifth
      toes were flexed at the proximal interphalangeal joint. We excised the
      osteochondroma and stabilized the metatarsophalangeal joints. After 3 years, the
      cosmetic and functional results were satisfactory. The subluxation at the
      metatarsophalangeal joints had resolved without treatment. Her Revised Foot
      Function Index score had improved from 141 preoperatively to 95 postoperatively,
      and her Manchester-Oxford Foot Questionnaire score had improved from 25 to 0.
      This case is a rare example of a large metatarsal osteochondroma in a growing
      child in which pressure from the tumor caused secondary forefoot deformities. The
      management of this case also shows the potential for the forefoot to remodel
      itself during adolescence, after the tumor has been resected and the joints
      stabilized.

PMID- 25979295
TI  - The Residency Training Experience in Podiatric Medicine and Surgery.
AB  - The podiatric medicine and surgery residency is currently characterized by 3
      years of comprehensive training. Contemporary issues have recently influenced the
      direction of training in the profession of podiatric medicine. Formal
      investigation into the residency training experience has, nonetheless, been
      limited. The purpose of the present study was to conduct a learning needs
      assessment of podiatric residency training. An electronic survey was developed,
      with comparable versions for program directors and residents. The specific topics
      investigated included the use of minimum activity volume numbers, learning
      resources, duty hours, strengths and weaknesses of residents, motivation of
      hosting student externship positions, noncognitive residency traits, meetings
      between residents and directors, resident satisfaction, and director
      satisfaction. A total of 197 program directors nationwide were sent the survey
      electronically, and 109 (53%) responded. Of 230 residents receiving the survey,
      159 (78%) responded. Several statistically significant differences, and notable
      similarities, were observed between the 2 groups encompassing many aspects of the
      survey. A majority opinion, among both directors and residents, was found that
      the use of procedural assessment tools might improve resident evaluation. The
      responding directors and residents agreed that the following 3 topics were
      weaknesses in podiatric training: practice management, biomechanics, and
      performing podiatric research. Direct feedback immediately after surgery was the
      most valuable learning resource reported by the residents. The results of our
      study reflect the current status of the podiatric medicine and surgery residency
      and could facilitate improvement in the residency training experience. 

PMID- 25979296
TI  - Field approach to mining-dump revegetation by application of sewage sludge co
      compost and a commercial biofertilizer.
AB  - An approach was devised for revegetation of a mining dump soil, sited in a
      semiarid region, with basic pH as well as Fe and Mn enrichment. A field
      experiment was conducted involving the use of co-compost (a mixture of urban
      sewage sludge and plant remains) along with a commercial biofertilizer (a gel
      suspension which contains arbuscular mycorrhizal fungus) to reinforce the
      benefits of the former. Four treatments were studied: unamended soil; application
      of conditioners separately and in combination. Pistachio, caper, rosemary, thyme
      and juniper were planted. We evaluated the effects of the treatments using soil
      quality (physicochemical properties, total content of hazardous elements,
      nutrient availability, microbial biomass and enzyme activities) and plant
      establishment indicators (survival, growth, vigor, nutrient content in leaves,
      nutrient balances and mycorrhizal root colonization). Thyme and juniper did not
      show a suitable survival rate (<50%) whereas 70-100% of the pistachio, rosemary
      and caper survived for at least 27 months. In unamended soil, plant growth was
      severely hampered by P, N, K and Zn deficiencies as well as Fe and Mn excess.
      Overall, the treatments affected the soil and plant indicators as follows:
      biofertilizer + co-compost > co-compost > biofertilizer > unamended. The
      application of co-compost was therefore essential with regard to improving soil
      fertility; furthermore, it increased leaf N and P content, whereas leaf Fe and Mn
      concentrations showed a decrease. The combined treatment, however, provided the
      best results. The positive interaction between the two soil conditioners might be
      related to the capacity of the biofertilizer to increase nutrient uptake from the
      composted residue, and to protect plants against Fe and Mn toxicity. 

PMID- 25979297
TI  - Sustainable rehabilitation of mining waste and acid mine drainage using
      geochemistry, mine type, mineralogy, texture, ore extraction and climate
      knowledge.
AB  - The oxidative dissolution of sulfidic minerals releases the extremely acidic
      leachate, sulfate and potentially toxic elements e.g., As, Ag, Cd, Cr, Cu, Hg,
      Ni, Pb, Sb, Th, U, Zn, etc. from different mine tailings and waste dumps. For the
      sustainable rehabilitation and disposal of mining waste, the sources and
      mechanisms of contaminant generation, fate and transport of contaminants should
      be clearly understood. Therefore, this study has provided a critical review on
      (1) recent insights in mechanisms of oxidation of sulfidic minerals, (2)
      environmental contamination by mining waste, and (3) remediation and
      rehabilitation techniques, and (4) then developed the GEMTEC conceptual
      model/guide [(bio)-geochemistry-mine type-mineralogy- geological texture-ore
      extraction process-climatic knowledge)] to provide the new scientific approach
      and knowledge for remediation of mining wastes and acid mine drainage. This study
      has suggested the pre-mining geological, geochemical, mineralogical and
      microtextural characterization of different mineral deposits, and post-mining
      studies of ore extraction processes, physical, geochemical, mineralogical and
      microbial reactions, natural attenuation and effect of climate change for
      sustainable rehabilitation of mining waste. All components of this model should
      be considered for effective and integrated management of mining waste and acid
      mine drainage. 

PMID- 25979298
TI  - Reply To the Editor, Re: Bicakli et al. Adjuvant chemotherapy may contribute to
      an increased risk for metabolic syndrome in patients with breast cancer. J Oncol
      Pharm Pract, published online September 2014. DOI: 10.1177/1078155214551315.

PMID- 25979299
TI  - Re: Bicakli et al. Adjuvant chemotherapy may contribute to an increased risk for
      metabolic syndrome in patients with breast cancer. J Oncol Pharm Pract, published
      online September 2014. DOI: 10.1177/1078155214551315.

PMID- 25979300
TI  - Video rigid flexing laryngoscope (RIFL) vs Miller laryngoscope for tracheal
      intubation during pediatric resuscitation by paramedics: a simulation study.
AB  - OBJECTIVES: Endotracheal intubation (ETI) is an essential resuscitation procedure
      in children. Video laryngoscopes have been developed to avoid intubation failures
      in a variety of scenarios, including cardiopulmonary resuscitation. We
      hypothesized that the video laryngoscope RIFL (AI Medical Devices, Inc,
      Williamston, MI) offers advantages in the ETI of a pediatric manikin while
      performing chest compressions (CCs). METHODS: Randomized nonblinded crossover
      simulation trial conducted among 132 paramedics with no prior experience with
      RIFL. Each participant performed intubations with Miller (MIL; Mercury Medical,
      Clearwater, FL) laryngoscope and RIFL in a PediaSIM CPR training manikin (FCAE
      HealthCare, Sarasota, FL) in 3 airway scenarios: (a) normal airway at rest
      (without concomitant CC), (b) normal airway with mechanically controlled CC, and
      (c) difficult airway with concomitant CC. The primary outcome was the time to
      intubation, and secondary one was the success of the intubation attempt. RESULTS:
      In the manikin at rest with normal airway, nearly all participants performed
      successful ETI both with MIL and RIFL, with similar intubation times. However, in
      the other scenarios (normal and difficult airway with uninterrupted CC), the
      results with RIFL were significantly better than with MIL (P < .05) for all the
      analyzed variables (success of first attempt, overall success rate, time to
      intubation, Cormac-Lehane grade, dental compression, and easy of intubation
      scores). CONCLUSIONS: In simulated child arrest scenarios with normal/difficult
      airway conditions and with concomitant mechanical CC, paramedics performed better
      with the RIFL video laryngoscope than with the standard MIL.

PMID- 25979301
TI  - The top 100 cited articles published in emergency medicine journals.
AB  - INTRODUCTION: Our objective was to identify trends and examine the
      characteristics of the top 100 cited articles in emergency medicine (EM)
      journals. METHODS: Scopus Library database was queried to determine the citations
      of the top 100 EM articles. A second database (Google Scholar) was used to gather
      the following information: number of authors, publication year, journal name,
      impact factor, country of origin, and article type (original article, review
      article, conference paper, or editorial). The top 100 cited articles were
      selected and analyzed by 2 independent investigators. RESULTS: We identified 100
      top-cited articles published in 6 EM journals, led by Annals of Emergency
      Medicine (65) and American Journal of Emergency Medicine (15). All top-cited
      articles were published between 1980 and 2009. The common areas of study were
      categorized as cardiovascular medicine, emergency department administration,
      toxicology, pain medicine, pediatrics, traumatology, and resuscitation. A
      statistically significant association was found between the journal impact factor
      and the number of top 100 cited articles (P < .005). CONCLUSION: The top-cited
      articles published in EM journals help us recognize the quality of the works,
      discoveries, and trends steering EM. Our analysis provides an insight to the
      prevalent areas of study being cited within our field of practice.

PMID- 25979302
TI  - Freestanding EDs and the emergency medicine resident: a valuable part of resident
      education?

PMID- 25979303
TI  - Rare cause of a common symptom: primary cardiac lymphoma.
AB  - Cardiac tumors may be symptomatic or found incidentally during evaluation for a
      seemingly unrelated problem or physical finding. Because symptoms may mimic other
      cardiac conditions, the clinical challenge is to consider the possibility of a
      cardiac tumor so that the appropriate diagnostic test(s) can be conducted. In
      this case, we describe an exceedingly rare cardiac tumor.

PMID- 25979304
TI  - Comparison of traditional otoscope to iPhone otoscope in the pediatric ED.
AB  - OBJECTIVE: Acute otitis media (AOM) is a common diagnosis under age 5 years. The
      primary objective was to determine if the CellScope Oto (CSO) improves tympanic
      membrane (TM) visualization and diagnostic precision compared to traditional
      otoscope. The secondary objective was to determine physician, patient, and parent
      device preference. METHODS: This is a prospective cross-sectional study of
      patients younger than 18 years presenting with ear pain, fever, or upper
      respiratory infection symptoms. Patients were examined by a resident then
      attending physician with a traditional wall-mounted otoscope followed by CSO.
      Each was blinded to the other's findings. Intrarater and interrater diagnostic
      agreement was compared. Physicians, parents, and patients were surveyed regarding
      their experience. RESULTS: A total of 51 patients completed the study. There was
      substantial intrarater agreement between traditional otoscope and CSO for
      residents: right ear (kappa = 0.74) and left ear (kappa = 0.74); CSO use changed
      reported view for 16 of 102 TM examinations (16%), of which 7 (7%) had clinically
      relevant change in diagnosis to/from AOM. There was substantial to almost-perfect
      agreement for attending physicians: right: (kappa = 0.86) and left (kappa =
      0.79); CSO use changed reported view for 12 (12%), with 6 (6%) clinically
      relevant. Resident/attending physician interrater agreement was moderate for both
      traditional otoscope (kappa = 0.40) and CSO (kappa = 0.47). Physicians agreed CSO
      was easy to use, enhanced TM visualization and diagnostic precision, and was a
      good teaching tool. Patients and parents also found the CSO images very helpful.
      CONCLUSION: CellScope Oto was preferred by physicians, patients, and parents. Use
      of the CSO changed final diagnosis a significant number of times, including
      clinically relevant changes to/from AOM.

PMID- 25979305
TI  - Transarterial hepatic chemoembolization with 70-150 um drug-eluting beads:
      assessment of clinical safety and liver toxicity profile.
AB  - PURPOSE: To assess the incidence and severity of adverse events (AEs) in the form
      of clinical symptoms and liver/biliary injuries (LBI) in patients with hepatic
      malignancies treated with transarterial chemoembolization using 70-150 MUm drug
      eluting beads (DEBs). MATERIALS AND METHODS: A single-institution retrospective
      analysis was performed in 37 patients (25 patients with hepatocellular carcinoma
      and 12 patients with metastatic disease) who underwent 43 sessions of
      segmental/subsegmental 70-150 MUm DEB transarterial chemoembolization with
      doxorubicin (38 sessions) or irinotecan (5 sessions). Patient inclusion criteria
      included the presence of the following lesion features: small diameter (<= 3 cm),
      hypovascular, or with areas of residual disease after other locoregional
      therapies. Mean tumor diameter was 3.4 cm. Mean imaging and clinical follow-up
      periods were 171 days and 373 days, respectively. Clinical, laboratory, and
      imaging data were used to identify and classify clinically symptomatic AEs per
      session and LBI per patient according to the National Cancer Institute Common
      Terminology Criteria for Adverse Events, version 4.03. Predictors for the
      occurrence of LBI were evaluated by logistic regression analysis. RESULTS: No
      grade 4 or 5 AEs were recorded. Clinically symptomatic AEs occurred in 29 (67.4%)
      sessions (grade 1-2, 28 sessions; grade 3, 1 session), all constituting
      postembolization syndrome. Asymptomatic LBI occurred in 11 (29.7%) patients
      (grade 1, 8 patients; grade 2, 3 patients). The mean time between 70-150 MUm DEB
      transarterial chemoembolization session and appearance of LBI was 71 days (range,
      21-223 d). No predictive factors for the development of LBI were identified.
      CONCLUSIONS: Transarterial chemoembolization with 70-150 MUm DEBs was considered
      safe in the present study population given the acceptably low incidence and
      severity of AEs.

PMID- 25979306
TI  - Comparing the effects of 17beta-oestradiol and the selective oestrogen receptor
      modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats.
AB  - BACKGROUND: Evidence suggests that oestrogen plays a protective role against the
      development and severity of schizophrenia. However, while oestrogen may be
      beneficial as a treatment in schizophrenia, its chronic use is associated with
      side-effects. Selective oestrogen receptor modulators (SERMs) may provide an
      alternative, however little is known about the mechanism underlying their effects
      in schizophrenia. METHODS: We investigated the effect of raloxifene and tamoxifen
      on dopaminergic-induced disruptions of prepulse inhibition (PPI). PPI measures
      sensorimotor gating and PPI disruptions are considered an endophenotype for
      schizophrenia. Adult female Sprague-Dawley rats were either intact,
      ovariectomized (OVX), OVX and 17beta-oestradiol-treated, OVX and raloxifene
      treated (low or high dose), or OVX and tamoxifen-treated (low or high dose).
      RESULTS: The dopamine D1/D2 receptor agonist, apomorphine (0, 0.1, 0.3 and
      1mg/kg), caused the expected dose-dependent disruption in PPI in intact and OVX
      rats. This PPI disruption was prevented in OVX rats treated with 17beta
      oestradiol, a high dose of raloxifene or a high dose of tamoxifen. In untreated
      OVX rats, average PPI was 55% after saline and 34% after 1mg/kg apomorphine
      treatment, a reduction of 21%. However, oestradiol-treated and raloxifene-treated
      OVX rats showed only a 7% PPI reduction, and tamoxifen-treated OVX rats had a 4%
      PPI reduction caused by apomorphine treatment. Startle amplitude was not
      different between the groups. CONCLUSION: The SERMs, raloxifene and tamoxifen,
      can prevent dopamine D1/D2 receptor-mediated disruptions of sensorimotor gating,
      similar to oestradiol. These data lend support for the use of SERMs as a
      treatment for schizophrenia.

PMID- 25979308
TI  - The Return of Delayed-Type Hypersensitivity Skin Testing for Coccidioidomycosis.
AB  - A skin test that detects dermal hypersensitivity in persons with past infection
      with Coccidioides species is again available for clinical use. Nearly all of the
      clinical studies with similar materials were published prior to the 1990s, and as
      a result, many practicing physicians will be unfamiliar with how skin testing for
      coccidioidomycosis might be useful in patient management or as a research tool.
      We review clinical and epidemiological studies with past skin test antigens, the
      composition of past and current skin test preparations with particular attention
      to differences in the preservatives, and how the current preparation could be
      used today. 

PMID- 25979307
TI  - Extended-Release Niacin Versus Fenofibrate in HIV-Infected Participants With Low
      High-Density Lipoprotein Cholesterol: Effects on Endothelial Function,
      Lipoproteins, and Inflammation.
AB  - BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C) are common
      in individuals with human immunodeficiency virus (HIV) infection, persist during
      antiretroviral therapy (ART), and are associated with increased cardiovascular
      disease (CVD) risk. METHODS: Virologically controlled participants without CVD on
      stable ART with low HDL-C (men <40 mg/dL, women <50 mg/dL) and triglycerides >150
      mg/dL were randomized to receive open-label extended-release niacin 1500 mg/day
      with aspirin 325 mg/day or fenofibrate 200 mg/day for 24 weeks. The primary
      endpoint was the week 24 within-arm change in brachial artery flow-mediated
      dilation (FMD) in participants with complete follow-up scans. RESULTS: Of 99
      participants, 74 had complete data (35 niacin, 39 fenofibrate). Median age was 45
      years, 77% were male, median CD4(+) count was 561 cells/uL, and brachial FMD was
      4.2%. Median HDL-C was 32 mg/dL for men and 38 mg/dL for women, low-density
      lipoprotein cholesterol was 103 mg/dL, and triglycerides were 232 mg/dL. In men,
      HDL-C increased a median of 3 mg/dL with niacin and 6.5 mg/dL with fenofibrate (P
      < .001 for both). In women, HDL-C increased a median of 16 mg/dL with niacin and
      8 mg/dL with fenofibrate (P = .08 for both). After 24 weeks, there was no
      significant change in FMD in either arm; the median (interquartile range) change
      was +0.6% (-1.6 to 2.3) with niacin (P = .28) and +0.5% (-1.0 to 3.0) with
      fenofibrate (P = .19). Neither treatment significantly affected C-reactive
      protein, interleukin 6, or D-dimer levels. CONCLUSIONS: Despite improvements in
      lipids, niacin or fenofibrate treatment for 24 weeks did not improve endothelial
      function or inflammatory markers in participants with well-controlled HIV
      infection and low HDL-C. CLINICAL TRIALS REGISTRATION: NCT01426438.

PMID- 25979309
TI  - Measles in Healthcare Facilities in the United States During the Postelimination
      Era, 2001-2014.
AB  - Between 2001 and 2014, 78 reported measles cases resulted from transmission in US
      healthcare facilities, and 29 healthcare personnel were infected from
      occupational exposure, 1 of whom transmitted measles to a patient. The economic
      impact of preventing and controlling measles transmission in healthcare
      facilities was $19 000-$114 286 per case. 

PMID- 25979310
TI  - Hepatitis C Management and the Infectious Diseases Physician: A Survey of Current
      and Anticipated Practice Patterns.
AB  - This query of North American infectious diseases physicians reviews current and
      anticipated practice patterns related to hepatitis C virus (HCV) care. Less than
      20% of survey respondents evaluated and/or treated >10 HCV-infected individuals
      in the past year. We review HCV practice patterns, barriers to management, and
      education among infectious diseases physicians. 

PMID- 25979311
TI  - White matter diffusion abnormalities in patients with psychogenic non-epileptic
      seizures.
AB  - The purpose of this study was to conduct a preliminary investigation of the white
      matter characteristics in patients with psychogenic non-epileptic seizures
      (PNES). Diffusion Tensor Imaging (DTI) data were collected at 3T in 16 patients
      with PNES and 16 age- and sex-matched healthy controls (HC). All patients with
      PNES had their diagnosis confirmed via video/EEG monitoring; HCs had no comorbid
      neurological or psychiatric conditions. DTI indices including fractional
      anisotropy (FA), and mean diffusivity (MD) were calculated and compared between
      patients with PNES and HCs using Tract-Based Spatial Statistics (TBSS).
      Significantly higher FA values were observed in patients with PNES in the left
      corona radiata, left internal and external capsules, left superior temporal
      gyrus, as well as left uncinate fasciculus (UF) (P<0.05; corrected for multiple
      comparisons). There was no significant change in other indices between patients
      with PNES and HCs. These findings suggest that patients with PNES have
      significantly altered white matter structural connectivity when compared to age-
      and sex-matched HCs. These abnormalities are present in left hemispheric regions
      associated with emotion regulation and motor pathways. While the relationship
      between the pathophysiology of PNES and these abnormalities is not entirely
      clear, this work provides an initial basis to guide future prospective studies. 

PMID- 25979312
TI  - [A prospective trial comparing consecutive series of open retropubic and robot
      assisted laparoscopic radical prostatectomy in a centre: Oncologic and functional
      outcomes].

PMID- 25979313
TI  - Gene Expression Regulation and Pathway Analysis After Valproic Acid and
      Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental
      Toxicity Assay.
AB  - Differentiating pluripotent stem cells in vitro have proven useful for the study
      of developmental toxicity. Here, we studied the effects of anticonvulsant drug
      exposure in a human embryonic stem cell (hESC)-based neurodevelopmental toxicity
      test (hESTn). During neural differentiation the cells were exposed, for either 1
      or 7 days, to noncytotoxic concentration ranges of valproic acid (VPA) or
      carbamazepine (CBZ), antiepileptic drugs known to cause neurodevelopmental
      toxicity. The effects observed on gene expression and correlated processes and
      pathways were in line with processes associated with neural development and
      pharmaceutical mode of action. In general, VPA showed a higher number of genes
      and molecular pathways affected than CBZ. The response kinetics differed between
      both compounds, with CBZ showing higher response magnitudes at day 1, versus VPA
      at day 7. With this study, we demonstrated the potential and biological relevance
      of the application of this hESC-based differentiation assay in combination with
      transcriptomics, as a tool to study neurodevelopmental toxicity. 

PMID- 25979314
TI  - Arsenic Induces Insulin Resistance in Mouse Adipocytes and Myotubes Via Oxidative
      Stress-Regulated Mitochondrial Sirt3-FOXO3a Signaling Pathway.
AB  - Chronic exposure to arsenic via drinking water is associated with an increased
      risk for development of type 2 diabetes mellitus (T2DM). This study investigates
      the role of mitochondrial oxidative stress protein Sirtuin 3 (Sirt3) and its
      targeting proteins in chronic arsenic-induced T2DM in mouse adipocytes and
      myotubes. The results show that chronic arsenic exposure significantly decreased
      insulin-stimulated glucose uptake (ISGU) in correlation with reduced expression
      of insulin-regulated glucose transporter type 4 (Glut4). Expression of Sirt3, a
      mitochondrial deacetylase, was dramatically decreased along with its associated
      transcription factor, forkhead box O3 (FOXO3a) upon arsenic exposure. A decrease
      in mitochondrial membrane potential (Deltapsim) was observed in both 3T3L1
      adipocytes and C2C12 myotubes treated by arsenic. Reduced FOXO3a activity by
      arsenic exhibited a decreased binding affinity to the promoters of both manganese
      superoxide dismutase (MnSOD) and peroxisome proliferator-activated receptor-gamma
      coactivator (PGC)-1alpha, a broad and powerful regulator of reactive oxygen
      species (ROS) metabolism. Forced expression of Sirt3 or MnSOD in mouse myotubes
      elevated Deltapsim and restored ISGU inhibited by arsenic exposure. Our results
      suggest that Sirt3/FOXO3a/MnSOD signaling plays a significant role in the
      inhibition of ISGU induced by chronic arsenic exposure. 

PMID- 25979315
TI  - Acaricidal activity of extracts from the leaves and aerial parts of Neoglaziovia
      variegata (Bromeliaceae) on the cattle tick Rhipicephalus (Boophilus) microplus.
AB  - This experiment was carried out to study the bioacaricidal activity of
      Neoglaziovia variegata against engorged females of Rhipicephalus (Boophilus)
      microplus. The mortality and fecundity of groups of engorged adult females
      exposed to different concentrations of ethanol, hexane, chloroform, and ethyl
      acetate extracts obtained from the leaves and aerial parts of N. variegata were
      evaluated, using three treatments with concentrations of 5, 10 e 25 mg/ml; two
      controls (distilled water and distilled water with drops of cremophor); with
      three replicates. The hexane extract of the leaves demonstrated significant
      results, presenting 94.1% inhibition of oviposition; 0.33% the average percentage
      of eclosion of eggs; and 99.8% of effectiveness. These results indicate N.
      variegata, particularly the hexane extract of leaves, as potential alternative
      control agents of R. (B.) microplus. Pharmacological and chemical studies are
      continuing in order to characterize the mechanism responsible for this effect.

PMID- 25979316
TI  - Rationale and design of the Randomized Evaluation to Measure Improvements in Non
      adherence from Low-Cost Devices (REMIND) trial.
AB  - BACKGROUND: Long-term adherence to prescription medications for the treatment of
      chronic disease remains low. While there are many contributors to suboptimal
      medication use, simple forgetfulness is widely believed to be central. Relatively
      simple devices may be a particularly cost-efficient and scalable way to promote
      adherence, however limited data exists about their ability to improve adherence
      in real-world settings. METHODS/DESIGN: The REMIND trial is a prospective, intent
      to-treat randomized control trial to evaluate the impact on medication adherence
      of three simple, low-cost devices (Take-N-Slide(TM), the RxTimerCap(TM), and a
      standard pillbox). In March 2014, we enrolled 53,480 individuals 18 to 64 years
      old taking one to three medications to treat chronic disease whose prescription
      drug benefits were administered by CVS Caremark. The study's primary outcome is
      optimal adherence over the 12-month period after randomization. Using a
      randomization ratio of 1:2 between control and each intervention arm, the study
      has more than 80% power with an alpha of 5% to detect a 1% difference in the rate
      of optimal adherence between intervention and control groups and across
      intervention arms. DISCUSSION: The REMIND trial is the first randomized study to
      rigorously evaluate the impact of simple, low-cost reminder devices on medication
      adherence. The results will inform comparative cost effectiveness studies of
      reminder systems in improving medication adherence and clinical outcomes.

PMID- 25979317
TI  - Empirically derived criteria cast doubt on the clinical significance of
      antidepressant-placebo differences.
AB  - Meta-analyses indicate that antidepressants are superior to placebos in
      statistical terms, but the clinical relevance of the differences has not been
      established. Previous suggestions of clinically relevant effect sizes have not
      been supported by empirical evidence. In the current paper we apply an empirical
      method that consists of comparing scores obtained on the Hamilton rating scale
      for depression (HAM-D) and scores from the Clinical Global Impressions
      Improvement (CGI-I) scale. This method reveals that a HAM-D difference of 3
      points is undetectable by clinicians using the CGI-I scale. A difference of 7
      points on the HAM-D, or an effect size of 0.875, is required to correspond to a
      rating of 'minimal improvement' on the CGI-I. By these criteria differences
      between antidepressants and placebo in randomised controlled trials, including
      trials conducted with people diagnosed with very severe depression, are not
      detectable by clinicians and fall far short of levels consistent with clinically
      observable minimal levels of improvement. Clinical significance should be
      considered alongside statistical significance when making decisions about the
      approval and use of medications like antidepressants. 

PMID- 25979319
TI  - Glucose-6-Phosphate Dehydrogenase Screening in Israel-Arab and Palestinian-Arab
      Neonates.
AB  - OBJECTIVE: To evaluate the frequency of glucose-6-phosphate dehydrogenase (G-6
      PD) deficiency, the incidence of clinically significant jaundice (any serum total
      bilirubin value >75th percentile on the hour-specific bilirubin nomogram), and
      the need for phototherapy in the pooled male Israeli-Arab and Palestinian-Arab
      population born at the Shaare Zedek Medical Center in Jerusalem, Israel. STUDY
      DESIGN: Quantitative G-6-PD enzyme testing of umbilical cord blood was performed
      during birth hospitalization. G-6-PD deficiency was defined as any G-6-PD value
      <7.0 U/gHb. Transcutaneous bilirubin was performed daily during birth
      hospitalization, with serum total bilirubin testing in those with a
      transcutaneous bilirubin value >75th percentile. RESULTS: Ten of 286 (3.5%)
      consecutively delivered male Arab newborns had G-6-PD deficiency. Clinically
      significant jaundice was higher in the population with G-6-PD deficiency compared
      with normal controls (relative risk, 3.45; 95% CI, 1.24-9.58). Thirty percent of
      the newborns with G-6-PD deficiency met American Academy of Pediatrics
      indications for phototherapy according to the high-risk (middle) curve on the
      phototherapy graph. CONCLUSION: The frequency of G-6-PD deficiency in the Arab
      neonatal population delivering at this medical center meets World Health
      Organization criteria for neonatal G-6-PD screening (3%-5%). As in other ethnic
      groups, clinically significant jaundice is more frequent in newborns of this
      ethnic group with G-6-PD deficiency compared with G-6-PD-normal controls.
      Neonatal G-6-PD screening for both males and females of this population subgroup,
      in conjunction with parental education regarding the dangers of the condition and
      its prophylaxis, has now been incorporated into our institution's routine G-6-PD
      screening program.

PMID- 25979318
TI  - A randomized controlled exercise training trial on insulin sensitivity in African
      American men: The ARTIIS study: Major category: study design, statistical design,
      study protocols.
AB  - BACKGROUND: Lack of regular physical activity at prescribed intensity levels is a
      modifiable risk factor for insulin resistance and the development of diabetes.
      African American men are at increased risk for developing diabetes and most
      African American men are not meeting the current recommended levels of physical
      activity. The primary objective of the Aerobic Plus Resistance Training and
      Insulin Resistance in African American Men (ARTIIS) study is to determine the
      effectiveness of an exercise training intervention aimed at reducing diabetes
      risk factors in African American men at risk for developing diabetes. METHODS:
      Insufficiently active 35-70 year old African American men with a family history
      of diabetes were eligible for the study. The 5-month randomized controlled trial
      assigns 116 men to an exercise training or healthy living control arm. The
      exercise training arm combines aerobic and resistance training according to the
      current national physical activity recommendations and is conducted in community
      (YMCA) facilities. The healthy living arm receives information promoting healthy
      lifestyle changes. OUTCOMES: Insulin response to an oral glucose load is the
      primary outcome measure, and changes in physiological parameters,
      cardiorespiratory fitness, strength, body composition, and psychological well
      being comprise the secondary outcomes. CONCLUSIONS: The ARTIIS study is one of
      the first adequately powered, rigorously designed studies to investigate the
      effects of an aerobic plus resistance exercise training program and to assess
      adherence to exercise training in community facilities, in African American men.

PMID- 25979320
TI  - A Congenital Intercostal Arteriovenous Fistula.

PMID- 25979321
TI  - Erythrocyte fatty acid status in a convenience sample of residents of the
      Guatemalan Pacific coastal plain.
AB  - We report the fatty acid composition, and in particular, the n-3 and n-6 long
      chain polyunsaturated fatty acids (LCPUFA), in erythrocytes from a convenience
      sample of 158 women and 135 schoolchildren residing in the southern Pacific Coast
      of Guatemala. Erythrocyte fatty acids were analyzed by gas-liquid chromatography
      with flame ionization detection and the profiles were expressed as a weight
      percent; the Omega-3 Index values were also determined. Schoolchildren had
      significantly higher mean ARA and total n-6 fatty acid levels than the women.
      Women had significantly higher EPA fatty acid levels than schoolchildren, but the
      reverse was true for DHA. For mean total n-3 fatty acid concentration, women and
      schoolchildren had similar values. The red cell weight percentages of selected
      fatty acids were also similar in women and schoolchildren. As compared with
      erythrocyte fatty acid data from developed countries, Guatemalan women and
      schoolchildren had consistently lower LCPUFA values. The traditional diet of
      Guatemalans living in the Pacific coastal region provided a worse erythrocyte
      fatty acid profile than that typically obtained from a Western diet. Additional
      fatty acid composition studies with associated dietary intake data in other
      inland locations may be useful for the interpretation of the nutritional status
      of Guatemalan children and adults. 

PMID- 25979322
TI  - General considerations regarding the in vitro and in vivo properties of block
      copolymer micelle products and their evaluation.
AB  - Block copolymer micelles are nanoparticles formed from block copolymers that
      comprise a hydrophilic polymer such as poly(ethylene glycol) and a poorly soluble
      polymer such as poly(amino acids). The design of block copolymer micelles is
      intended to regulate the in vivo pharmacokinetics, stability, and distribution
      profiles of an entrapped or block copolymer-linked active substance. Several
      block copolymer micelle products are currently undergoing clinical development;
      however, a major challenge in the development and evaluation of such products is
      identification of the physicochemical properties that affect the properties of
      the drug product in vivo. Here we review the overall in vitro and in vivo
      characteristics of block copolymer micelle products with a focus on the products
      currently under clinical investigation. We present examples of methods suitable
      for the evaluation of the physicochemical properties, non-clinical
      pharmacokinetics, and safety of block copolymer micelle products. 

PMID- 25979323
TI  - Enhanced delivery of liposomes to lung tumor through targeting interleukin-4
      receptor on both tumor cells and tumor endothelial cells.
AB  - A growing body of evidence suggests that pathological lesions express tissue
      specific molecular targets or biomarkers within the tissue. Interleukin-4
      receptor (IL-4R) is overexpressed in many types of cancer cells, including lung
      cancer. Here we investigated the properties of IL-4R-binding peptide-1 (IL4RPep
      1), a CRKRLDRNC peptide, and its ability to target the delivery of liposomes to
      lung tumor. IL4RPep-1 preferentially bound to H226 lung tumor cells which express
      higher levers of IL-4R compared to H460 lung tumor cells which express less IL
      4R. Mutational analysis revealed that C1, R2, and R4 residues of IL4RPep-1 were
      the key binding determinants. IL4RPep-1-labeled liposomes containing doxorubicin
      were more efficiently internalized in H226 cells and effectively delivered
      doxorubicin into the cells compared to unlabeled liposomes. In vivo fluorescence
      imaging of nude mice subcutaneously xenotransplanted with H226 tumor cells
      indicated that IL4RPep-1-labeled liposomes accumulate more efficiently in the
      tumor and inhibit tumor growth more effectively compared to unlabeled liposomes.
      Interestingly, expression of IL-4R was high in vascular endothelial cells of
      tumor, while little was detected in vascular endothelial cells of control organs
      including the liver. IL-4R expression in cultured human vascular endothelial
      cells was also up-regulated when activated by a pro-inflammatory cytokine tumor
      necrosis factor-alpha. Moreover, the up-regulation of IL-4R expression was
      observed in primary human lung cancer tissues. These results indicate that IL-4R
      targeting nanocarriers may be a useful strategy to enhance drug delivery through
      the recognition of IL-4R in both tumor cells and tumor endothelial cells. 

PMID- 25979325
TI  - Co-delivery of chemosensitizing siRNA and an anticancer agent via multiple
      monocomplexation-induced hydrophobic association.
AB  - Synergistic combination of gene targeting and chemotherapy by co-delivering siRNA
      and anticancer drugs has widely been investigated to develop siRNA-based
      therapeutics for cancer treatment. Despite clinical potential of this approach,
      big challenges still remain such as delivery efficiency or
      stability/biocompatibility of the siRNA delivery system. Here we report a simple
      and biocompatible co-delivering formulation based on a unique complexation
      method, i.e., multiple monocomplexation-induced hydrophobic association between
      Bcl-2 targeting siRNA and a monocationic anticancer agent (benzethonium chloride,
      BZT). A colloidal formulation of the hydrophobically associated multiple
      monocomplex (HMplex) composed of siRNA, BZT and Pluronic F-68 was spontaneously
      constructed by physical mixing of the ternary constituents. In vitro and in vivo
      studies revealed that the ternary HMplex with a low charge ratio (N/P=4)
      possesses a tightly complexed stable nanostructure with Pluronic surface and
      small colloidal size less than 10nm, which allowed for 1) suitable protection of
      siRNA in serum-rich physiological environment, 2) efficient intracellular
      transfection into the cytoplasm, and 3) successful peritumoral co-delivery into
      the tumor tissue with dense interstitial matrix. Compared to non-targeting
      HMplexes between scrambled siRNA and BZT, Bcl-2 targeting HMplexes enhanced
      significantly both mRNA down-regulation by siRNA and apoptosis induction by BZT,
      and thus greatly suppressed the tumor volume when administered to highly
      aggressive and resistant human breast cancer xenografts (MDA-MB-231) in mice.
      These results elucidate that the co-complexed siRNA and BZT were liberated by
      intracellular decomplexation to trigger a synergistically combined therapeutic
      action. The successful siRNA/chemodrug co-delivery in vivo via peritumoral route
      and the greatly promoted therapeutic efficacy thereby represent the clinical
      potential of HMplexes for adjuvant locoregional cancer treatment by gene-targeted
      combination therapy. 

PMID- 25979324
TI  - Cancer cell surface induced peptide folding allows intracellular translocation of
      drug.
AB  - Many lead molecules identified in drug discovery campaigns are eliminated from
      consideration due to poor solubility and low cell permeability. These orphaned
      molecules could have clinical value if solubilized and delivered properly. SVS-1
      is a de novo designed peptide that preferentially folds at the surface of tumor
      cells, adopting a beta-hairpin conformation that rapidly translocates into the
      cytoplasm, and ultimately nucleus, of cells. SVS-1 is stable in serum and small
      molecules attached to the peptide are effectively delivered to cancer cells via
      mechanisms involving physical translocation and, to a lesser extent, clathrin
      dependent endocytosis. For example, ligating the model hydrophobic drug
      Paclitaxel (PTX) to SVS-1 improved its aqueous solubility by ~1000-fold and
      successfully delivered and released PTX to cancer cells in vitro and tumors in
      vivo without toxic adjuvants. These results suggest that SVS-1 can serve as a
      simple, effective delivery platform for molecules with poor solubility and
      permeability. 

PMID- 25979326
TI  - Remote-controlled eradication of astrogliosis in spinal cord injury via
      electromagnetically-induced dexamethasone release from "smart" nanowires.
AB  - We describe a system to deliver drugs to selected tissues continuously, if
      required, for weeks. Drugs can be released remotely inside the small animals
      using pre-implanted, novel vertically aligned electromagnetically-sensitive
      polypyrrole nanowires (PpyNWs). Approximately 1-2mm(2) dexamethasone (DEX) doped
      PpyNWs was lifted on a single drop of sterile water by surface tension, and
      deposited onto a spinal cord lesion in glial fibrillary acidic protein-luc
      transgenic mice (GFAP-luc mice). Overexpression of GFAP is an indicator of
      astrogliosis/neuroinflammation in CNS injury. The corticosteroid DEX, a powerful
      ameliorator of inflammation, was released from the polymer by external
      application of an electromagnetic field for 2h/day for a week. The GFAP signal,
      revealed by bioluminescent imaging in the living animal, was significantly
      reduced in treated animals. At 1week, GFAP was at the edge of detection, and in
      some experimental animals, completely eradicated. We conclude that the
      administration of drugs can be controlled locally and non-invasively, opening the
      door to many other known therapies, such as the cases that dexamethasone cannot
      be safely applied systemically in large concentrations. 

PMID- 25979328
TI  - Oral films as breakthrough tools for oral delivery of proteins/peptides.
AB  - Therapeutic proteins and peptides demonstrate unique, peerless, pharmacological
      characteristics such as high specificity to receptors and superior biological
      mimicking of physiological mechanisms, resulting in a better therapeutic index
      compared to conventional chemical-derived drugs. However, proteins also present
      inherent bioavailability limitations. Thus, this paper proposes several effective
      tools to improve protein/peptide drugs stability, permeability and
      pharmacokinetics with special emphasis on oral polymeric films as oral delivery
      platforms. Indeed, oral films present inherent characteristics that can greatly
      enhance biological performance of proteins and peptides and patient compliance
      along with other advantages that are critically discussed in this review. A
      rational choice of excipients addressed in and manufacture processes are also
      focused. In addition, possible toxicity issues to be overtaken and critical
      analysis regarding current market tendencies respecting oral films and
      protein/peptides along with future prospects are disclosed. 

PMID- 25979327
TI  - Lipid nanoparticle delivery of a microRNA-145 inhibitor improves experimental
      pulmonary hypertension.
AB  - Therapies that exploit RNA interference (RNAi) hold great potential for improving
      disease outcomes. However, there are several challenges that limit the
      application of RNAi therapeutics. One of the most important challenges is
      effective delivery of oligonucleotides to target cells and reduced delivery to
      non-target cells. We have previously developed a functionalized cationic
      lipopolyamine (Star:Star-mPEG-550) for in vivo delivery of siRNA to pulmonary
      vascular cells. This optimized lipid formulation enhances the retention of siRNA
      in mouse lungs and achieves significant knockdown of target gene expression for
      at least 10days following a single intravenous injection. Although this suggests
      great potential for developing lung-directed RNAi-based therapies, the
      application of Star:Star-mPEG mediated delivery of RNAi based therapies for
      pulmonary vascular diseases such as pulmonary arterial hypertension (PAH) remains
      unknown. We identified differential expression of several microRNAs known to
      regulate cell proliferation, cell survival and cell fate that are associated with
      development of PAH, including increased expression of microRNA-145 (miR-145).
      Here we test the hypothesis that Star:Star-mPEG mediated delivery of an antisense
      oligonucleotide against miR-145 (antimiR-145) will improve established PAH in
      rats. We performed a series of experiments testing the in vivo distribution,
      toxicity, and efficacy of Star:Star-mPEG mediated delivery of antimiR-145 in rats
      with Sugen-5416/hypoxia induced PAH. We showed that after subchronic therapy of
      three intravenous injections over 5weeks at 2mg/kg, antimiR-145 accumulated in
      rat lung tissue and reduced expression of endogenous miR-145. Using a novel in
      situ hybridization approach, we demonstrated substantial distribution of antimiR
      145 in the lungs as well as the liver, kidney, and spleen. We assessed toxic
      effects of Star:Star-mPEG/antimiR-145 with serial complete blood counts of
      leukocytes and serum metabolic panels, gross pathology, and histopathology and
      did not detect significant off-target effects. AntimiR-145 reduced the degree of
      pulmonary arteriopathy, reduced the severity of pulmonary hypertension, and
      reduced the degree of cardiac dysfunction. The results establish effective and
      low toxicity of lung delivery of a miRNA-145 inhibitor using functionalized
      cationic lipopolyamine nanoparticles to repair pulmonary arteriopathy and improve
      cardiac function in rats with severe PAH. 

PMID- 25979329
TI  - Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol
      transdermal drug delivery systems.
AB  - The objective of this study was to develop a level A in vitro-in vivo correlation
      (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery
      systems (TDDS). In vitro drug permeation studies across human skin were carried
      out to obtain the percent of estradiol permeation from marketed products. The in
      vivo time versus plasma concentration data of three estradiol TDDS at drug
      loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100MUg/day,
      respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in
      vivo drug absorption in postmenopausal women. The IVIVC between the in vitro
      percent of drug permeation (X) and in vivo percent of drug absorption (Y) for
      these three estradiol TDDS was constructed using GastroPlus(r) software. There
      was a high correlation (R(2)=1.0) with a polynomial regression of Y=
      0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal
      validation whereas another two products of the same formulation design (with
      delivery rates of 60 and 100MUg/day) were used for external validation. The
      predicted estradiol serum concentrations (convoluted from in vitro skin
      permeation data) were compared with the observed serum concentrations for the
      respective products. The developed IVIVC model passed both the internal and
      external validations as the prediction errors (%PE) for Cmax and AUC were less
      than 15%. When another marketed estradiol TDDS with a delivery rate of 100MUg/day
      but with a slight variation in formulation design was chosen, it did not pass
      external validation indicating the product-specific nature of IVIVC model.
      Results suggest that the IVIVC model developed in this study can be used to
      successfully predict the in vivo performance of the same estradiol TDDS with in
      vivo delivery rates ranging from 25 to 100MUg/day. 

PMID- 25979330
TI  - A needle-free technique for interstitial fluid sample acquisition using a lorentz
      force actuated jet injector.
AB  - We present a novel method of quickly acquiring dermal interstitial fluid (ISF)
      samples using a Lorentz-force actuated needle-free jet injector. The feasibility
      of the method is first demonstrated on post-mortem porcine tissue. The jet
      injector is used to first inject a small volume of physiological saline to breach
      the skin, and the back-drivability of the actuator is utilized to create negative
      pressure in the ampoule and collect ISF. The effect of the injection and
      extraction parameters on sample dilution and extracted volumes is investigated. A
      simple finite element model is developed to demonstrate why this acquisition
      method results in faster extractions than conventional sampling methods. Using
      this method, we are able to collect a sample that contains up to 3.5% ISF in 3.1s
      from post-mortem skin. The trends revealed from experimentation on post-mortem
      skin are then used to identify the parameters for a live animal study. The
      feasibility of the acquisition process is successfully demonstrated using live
      rats; the process is revealed to extract samples that have been diluted by a
      factor of 111-125. 

PMID- 25979331
TI  - Methyl CpG Binding Protein 2 Gene Disruption Augments Tonic Currents of gamma
      Aminobutyric Acid Receptors in Locus Coeruleus Neurons: IMPACT ON NEURONAL
      EXCITABILITY AND BREATHING.
AB  - People with Rett syndrome and mouse models show autonomic dysfunction involving
      the brain stem locus coeruleus (LC). Neurons in the LC of Mecp2-null mice are
      overly excited, likely resulting from a defect in neuronal intrinsic membrane
      properties and a deficiency in GABA synaptic inhibition. In addition to the
      synaptic GABA receptors, there is a group of GABAA receptors (GABAARs) that is
      located extrasynaptically and mediates tonic inhibition. Here we show evidence
      for augmentation of the extrasynaptic GABAARs in Mecp2-null mice. In brain
      slices, exposure of LC neurons to GABAAR agonists increased tonic currents that
      were blocked by GABAAR antagonists. With 10 MUm GABA, the bicuculline-sensitive
      tonic currents were ~4-fold larger in Mecp2-null LC neurons than in the WT.
      Single-cell PCR analysis showed that the delta subunit, the principal subunit of
      extrasynaptic GABAARs, was present in LC neurons. Expression levels of the delta
      subunit were ~50% higher in Mecp2-null neurons than in the WT. Also increased in
      expression in Mecp2-null mice was another extrasynaptic GABAAR subunit, alpha6,
      by ~4-fold. The delta subunit-selective agonists 4,5,6,7-tetrahydroisoxazolo[5,4
      c]pyridin-3-ol hydrochloride and 4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridin-3
      yl]]benzamide activated the tonic GABAA currents in LC neurons and reduced
      neuronal excitability to a greater degree in Mecp2-null mice than in the WT.
      Consistent with these findings, in vivo application of 4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride alleviated breathing
      abnormalities of conscious Mecp2-null mice. These results suggest that
      extrasynaptic GABAARs seem to be augmented with Mecp2 disruption, which may be a
      compensatory response to the deficiency in GABAergic synaptic inhibition and
      allows control of neuronal excitability and breathing abnormalities. 

PMID- 25979332
TI  - Loss of alpha1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation:
      IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR
      HETEROMERIZATION AND CELLULAR SIGNALING.
AB  - Core fucosylation is catalyzed by alpha1,6-fucosyltransferase (FUT8), which
      transfers a fucose residue to the innermost GlcNAc residue via alpha1,6-linkage
      on N-glycans in mammals. We previously reported that Fut8-knock-out (Fut8(-/-))
      mice showed a schizophrenia-like phenotype and a decrease in working memory. To
      understand the underlying molecular mechanism, we analyzed early form long term
      potentiation (E-LTP), which is closely related to learning and memory in the
      hippocampus. The scale of E-LTP induced by high frequency stimulation was
      significantly decreased in Fut8(-/-) mice. Tetraethylammonium-induced LTP showed
      no significant differences, suggesting that the decline in E-LTP was caused by
      postsynaptic events. Unexpectedly, the phosphorylation levels of
      calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of
      learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice.
      The expression levels of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice,
      although there were no significant differences in the total expression levels,
      implicating that AMPARs without core fucosylation might exist in an active state.
      The activation of AMPARs was further confirmed by Fura-2 calcium imaging using
      primary cultured neurons. Taken together, loss of core fucosylation on AMPARs
      enhanced their heteromerization, which increase sensitivity for postsynaptic
      depolarization and persistently activate N-methyl-d-aspartate receptors as well
      as Ca(2+) influx and CaMKII and then impair LTP. 

PMID- 25979333
TI  - Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled
      Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions.
AB  - Neuronal calcium sensor-1 (NCS-1) is the primordial member of the neuronal
      calcium sensor family of EF-hand Ca(2+)-binding proteins. It interacts with both
      the G-protein-coupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its
      internalization and surface expression, and the cognate kinases GRK1 and GRK2.
      Determination of the crystal structures of Ca(2+)/NCS-1 alone and in complex with
      peptides derived from D2R and GRK1 reveals that the differential recognition is
      facilitated by the conformational flexibility of the C-lobe-binding site. We find
      that two copies of the D2R peptide bind within the hydrophobic crevice on
      Ca(2+)/NCS-1, but only one copy of the GRK1 peptide binds. The different binding
      modes are made possible by the C-lobe-binding site of NCS-1, which adopts
      alternative conformations in each complex. C-terminal residues Ser-178-Val-190
      act in concert with the flexible EF3/EF4 loop region to effectively form
      different peptide-binding sites. In the Ca(2+)/NCS-1.D2R peptide complex, the C
      terminal region adopts a 310 helix-turn-310 helix, whereas in the GRK1 peptide
      complex it forms an alpha-helix. Removal of Ser-178-Val-190 generated a C
      terminal truncation mutant that formed a dimer, indicating that the NCS-1 C
      terminal region prevents NCS-1 oligomerization. We propose that the flexible
      nature of the C-terminal region is essential to allow it to modulate its protein
      binding sites and adapt its conformation to accommodate both ligands. This
      appears to be driven by the variability of the conformation of the C-lobe-binding
      site, which has ramifications for the target specificity and diversity of NCS-1. 

PMID- 25979334
TI  - Structure and Biophysical Characterization of the S-Adenosylmethionine-dependent
      O-Methyltransferase PaMTH1, a Putative Enzyme Accumulating during Senescence of
      Podospora anserina.
AB  - Low levels of reactive oxygen species (ROS) act as important signaling molecules,
      but in excess they can damage biomolecules. ROS regulation is therefore of key
      importance. Several polyphenols in general and flavonoids in particular have the
      potential to generate hydroxyl radicals, the most hazardous among all ROS.
      However, the generation of a hydroxyl radical and subsequent ROS formation can be
      prevented by methylation of the hydroxyl group of the flavonoids. O-Methylation
      is performed by O-methyltransferases, members of the S-adenosyl-l-methionine
      (SAM)-dependent O-methyltransferase superfamily involved in the secondary
      metabolism of many species across all kingdoms. In the filamentous fungus
      Podospora anserina, a well established aging model, the O-methyltransferase
      (PaMTH1) was reported to accumulate in total and mitochondrial protein extracts
      during aging. In vitro functional studies revealed flavonoids and in particular
      myricetin as its potential substrate. The molecular architecture of PaMTH1 and
      the mechanism of the methyl transfer reaction remain unknown. Here, we report the
      crystal structures of PaMTH1 apoenzyme, PaMTH1-SAM (co-factor), and PaMTH1-S
      adenosyl homocysteine (by-product) co-complexes refined to 2.0, 1.9, and 1.9 A,
      respectively. PaMTH1 forms a tight dimer through swapping of the N termini. Each
      monomer adopts the Rossmann fold typical for many SAM-binding methyltransferases.
      Structural comparisons between different O-methyltransferases reveal a strikingly
      similar co-factor binding pocket but differences in the substrate binding pocket,
      indicating specific molecular determinants required for substrate selection.
      Furthermore, using NMR, mass spectrometry, and site-directed active site
      mutagenesis, we show that PaMTH1 catalyzes the transfer of the methyl group from
      SAM to one hydroxyl group of the myricetin in a cation-dependent manner. 

PMID- 25979336
TI  - Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and
      Differentiation of T Follicular Helper Cells.
AB  - T follicular helper (Tfh) cells support differentiation of B cells to plasma
      cells and high affinity antibody production in germinal centers (GCs), and Tfh
      differentiation requires the function of B cell lymphoma 6 (BCL6). We have now
      discovered that early growth response gene 2 (EGR2) and EGR3 directly regulate
      the expression of Bcl6 in Tfh cells, which is required for their function in
      regulation of GC formation. In the absence of EGR2 and -3, the expression of BCL6
      in Tfh cells is defective, leading to impaired differentiation of Tfh cells,
      resulting in a failure to form GCs following virus infection and defects in
      production of antiviral antibodies. Enforced expression of BCL6 in EGR2/3
      deficient CD4 T cells partially restored Tfh differentiation and GC formation in
      response to virus infection. Our findings demonstrate a novel function of EGR2/3
      that is important for Tfh cell development and Tfh cell-mediated B cell immune
      responses. 

PMID- 25979335
TI  - Endothelial Angiogenesis and Barrier Function in Response to Thrombin Require
      Ca2+ Influx through the Na+/Ca2+ Exchanger.
AB  - Thrombin acts on the endothelium by activating protease-activated receptors
      (PARs). The endothelial thrombin-PAR system becomes deregulated during
      pathological conditions resulting in loss of barrier function and a pro
      inflammatory and pro-angiogenic endothelial phenotype. We reported recently that
      the ion transporter Na(+)/Ca(2+) exchanger (NCX) operating in the Ca(2+)-influx
      (reverse) mode promoted ERK1/2 activation and angiogenesis in vascular
      endothelial growth factor-stimulated primary human vascular endothelial cells.
      Here, we investigated whether Ca(2+) influx through NCX was involved in ERK1/2
      activation, angiogenesis, and endothelial barrier dysfunction in response to
      thrombin. Reverse-mode NCX inhibitors and RNAi-mediated NCX1 knockdown attenuated
      ERK1/2 phosphorylation in response to thrombin or an agonist of PAR-1, the main
      endothelial thrombin receptor. Conversely, promoting reverse-mode NCX by
      suppressing Na(+)-K(+)-ATPase activity enhanced ERK1/2 activation. Reverse-mode
      NCX inhibitors and NCX1 siRNA suppressed thrombin-induced primary human vascular
      endothelial cell angiogenesis, quantified as proliferation and tubular
      differentiation. Reverse-mode NCX inhibitors or NCX1 knockdown preserved barrier
      integrity upon thrombin stimulation in vitro. Moreover, the reverse-mode NCX
      inhibitor SEA0400 suppressed Evans' blue albumin extravasation to the lung and
      kidneys and attenuated edema formation and ERK1/2 activation in the lungs of mice
      challenged with a peptide activator of PAR-1. Mechanistically, thrombin-induced
      ERK1/2 activation required NADPH oxidase 2-mediated reactive oxygen species (ROS)
      production, and reverse-mode NCX inhibitors and NCX1 siRNA suppressed thrombin
      induced ROS production. We propose that reverse-mode NCX is a novel mechanism
      contributing to thrombin-induced angiogenesis and hyperpermeability by mediating
      ERK1/2 activation in a ROS-dependent manner. Targeting reverse-mode NCX could be
      beneficial in pathological conditions involving unregulated thrombin signaling. 

PMID- 25979337
TI  - Integration of Fourier Transform Infrared Spectroscopy, Fluorescence
      Spectroscopy, Steady-state Kinetics and Molecular Dynamics Simulations of
      Galphai1 Distinguishes between the GTP Hydrolysis and GDP Release Mechanism.
AB  - Galpha subunits are central molecular switches in cells. They are activated by G
      protein-coupled receptors that exchange GDP for GTP, similar to small GTPase
      activation mechanisms. Galpha subunits are turned off by GTP hydrolysis. For the
      first time we employed time-resolved FTIR difference spectroscopy to investigate
      the molecular reaction mechanisms of Galphai1. FTIR spectroscopy is a powerful
      tool that monitors reactions label free with high spatio-temporal resolution. In
      contrast to common multiple turnover assays, FTIR spectroscopy depicts the single
      turnover GTPase reaction without nucleotide exchange/Mg(2+) binding bias. Global
      fit analysis resulted in one apparent rate constant of 0.02 s(-1) at 15  degrees
      C. Isotopic labeling was applied to assign the individual phosphate vibrations
      for alpha-, beta-, and gamma-GTP (1243, 1224, and 1156 cm(-1), respectively),
      alpha- and beta-GDP (1214 and 1134/1103 cm(-1), respectively), and free phosphate
      (1078/991 cm(-1)). In contrast to Ras . GAP catalysis, the bond breakage of the
      beta-gamma-phosphate but not the Pi release is rate-limiting in the GTPase
      reaction. Complementary common GTPase assays were used. Reversed phase HPLC
      provided multiple turnover rates and tryptophan fluorescence provided nucleotide
      exchange rates. Experiments were complemented by molecular dynamics simulations.
      This broad approach provided detailed insights at atomic resolution and allows
      now to identify key residues of Galphai1 in GTP hydrolysis and nucleotide
      exchange. Mutants of the intrinsic arginine finger (Galphai1-R178S) affected
      exclusively the hydrolysis reaction. The effect of nucleotide binding (Galphai1
      D272N) and Ras-like/all-alpha interface coordination (Galphai1-D229N/Galphai1
      D231N) on the nucleotide exchange reaction was furthermore elucidated.

PMID- 25979338
TI  - During Cytochrome c Maturation CcmI Chaperones the Class I Apocytochromes until
      the Formation of Their b-Type Cytochrome Intermediates.
AB  - The c-type cytochromes are electron transfer proteins involved in energy
      transduction. They have heme-binding (CXXCH) sites that covalently ligate heme b
      via thioether bonds and are classified into different classes based on their
      protein folds and the locations and properties of their cofactors. Rhodobacter
      capsulatus produces various c-type cytochromes using the cytochrome c maturation
      (Ccm) System I, formed from the CcmABCDEFGHI proteins. CcmI, a component of the
      heme ligation complex CcmFHI, interacts with the heme-handling protein CcmE and
      chaperones apocytochrome c2 by binding its C-terminal helix. Whether CcmI also
      chaperones other c-type apocytochromes, and the effects of heme on these
      interactions were unknown previously. Here, we purified different classes of
      soluble and membrane-bound c-type apocytochromes (class I, c2 and c1, and class
      II c') and investigated their interactions with CcmI and apoCcmE. We report that,
      in the absence of heme, CcmI and apoCcmE recognized different classes of c-type
      apocytochromes with different affinities (nM to MUM KD values). When present,
      heme induced conformational changes in class I apocytochromes (e.g. c2) and
      decreased significantly their high affinity for CcmI. Knowing that CcmI does not
      interact with mature cytochrome c2 and that heme converts apocytochrome c2 into
      its b-type derivative, these findings indicate that CcmI holds the class I
      apocytochromes (e.g. c2) tightly until their noncovalent heme-containing b-type
      cytochrome-like intermediates are formed. We propose that these intermediates are
      subsequently converted into mature cytochromes following the covalent ligation of
      heme via the remaining components of the Ccm complex.

PMID- 25979339
TI  - Trans-regulation of Syndecan Functions by Hetero-oligomerization.
AB  - Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to
      interact through their transmembrane domains to form non-covalently linked
      homodimers, a process essential for their individual functions. Because all
      syndecan transmembrane domains are highly conserved and thus might mediate
      interactions between different members of the syndecan family, we investigated
      syndecan interactions in detail. All recombinant syndecan-2 and -4 protein
      variants containing the transmembrane domain formed not only sodium dodecyl
      sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers.
      Biochemical and structural data revealed that recombinant syndecan-2 and -4
      formed intermolecular interactions in vitro, and the GXXXG motif in transmembrane
      domain mediated this interaction. When exogenously expressed in rat embryonic
      fibroblasts, syndecan-2 interacted with syndecan-4 and vice versa. Furthermore,
      bimolecular fluorescence complementation-based assay demonstrated specific hetero
      molecular interactions between syndecan-2 and -4, supporting hetero-oligomer
      formation of syndecans in vivo. Interestingly, hetero-oligomerization
      significantly reduced syndecan-4-mediated cellular processes such as protein
      kinase Calpha activation and protein kinase Calpha-mediated cell adhesion as well
      as syndecan-2-mediated tumorigenic activities in colon cancer cells such as
      migration and anchorage-independent growth. Taken together, these data provide
      evidence that hetero-oligomerization produces distinct syndecan functions and
      offer insights into the underlying signaling mechanisms of syndecans. 

PMID- 25979340
TI  - Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon
      Cells.
AB  - Lysyl oxidases (LOXs) are a family of copper-dependent oxido-deaminases that can
      modify the side chain of lysyl residues in collagen and elastin, thereby leading
      to the spontaneous formation of non-reducible aldehyde-derived interpolypeptide
      chain cross-links. The consequences of LOX inhibition in producing lathyrism are
      well documented, but the consequences on collagen fibril formation are less
      clear. Here we used beta-aminoproprionitrile (BAPN) to inhibit LOX in tendon-like
      constructs (prepared from human tenocytes), which are an experimental model of
      cell-mediated collagen fibril formation. The improvement in structure and
      strength seen with time in control constructs was absent in constructs treated
      with BAPN. As expected, BAPN inhibited the formation of aldimine-derived cross
      links in collagen, and the constructs were mechanically weak. However, an
      unexpected finding was that BAPN treatment led to structurally abnormal collagen
      fibrils with irregular profiles and widely dispersed diameters. Of special
      interest, the abnormal fibril profiles resembled those seen in some Ehlers-Danlos
      Syndrome phenotypes. Importantly, the total collagen content developed normally,
      and there was no difference in COL1A1 gene expression. Collagen type V, decorin,
      fibromodulin, and tenascin-X proteins were unaffected by the cross-link
      inhibition, suggesting that LOX regulates fibrillogenesis independently of these
      molecules. Collectively, the data show the importance of LOX for the mechanical
      development of early collagenous tissues and that LOX is essential for correct
      collagen fibril shape formation. 

PMID- 25979341
TI  - The Proteasome Inhibitor Carfilzomib Suppresses Parathyroid Hormone-induced
      Osteoclastogenesis through a RANKL-mediated Signaling Pathway.
AB  - Parathyroid hormone (PTH) induces osteoclast formation and activity by increasing
      the ratio of RANKL/OPG in osteoblasts. The proteasome inhibitor carfilzomib (CFZ)
      has been used as an effective therapy for multiple myeloma via the inhibition of
      pathologic bone destruction. However, the effect of combination of PTH and CFZ on
      osteoclastogenesis is unknown. We now report that CFZ inhibits PTH-induced RANKL
      expression and secretion without affecting PTH inhibition of OPG expression, and
      it does so by blocking HDAC4 proteasomal degradation in osteoblasts. Furthermore,
      we used different types of culture systems, including co-culture, indirect co
      culture, and transactivation, to assess the effect of CFZ on PTH action to induce
      osteoclastogenesis. Our results demonstrated that CFZ blocks PTH-induced
      osteoclast formation and bone resorption by its additional effect to inhibit
      RANKL-mediated IkappaB degradation and NF-kappaB activation in osteoclasts. This
      study showed for the first time that CFZ targets both osteoblasts and osteoclasts
      to suppress PTH-induced osteoclast differentiation and bone resorption. These
      findings warrant further investigation of this novel combination in animal models
      of osteoporosis and in patients. 

PMID- 25979342
TI  - Synergistic Binding of Vascular Endothelial Growth Factor-A and Its Receptors to
      Heparin Selectively Modulates Complex Affinity.
AB  - Angiogenesis is a highly regulated process orchestrated by the VEGF system.
      Heparin/heparan sulfate proteoglycans and neuropilin-1 (NRP-1) have been
      identified as co-receptors, yet the mechanisms of action have not been fully
      defined. In the present study, we characterized molecular interactions between
      receptors and co-receptors, using surface plasmon resonance and in vitro binding
      assays. Additionally, we demonstrate that these binding events are relevant to
      VEGF activity within endothelial cells. We defined interactions and structural
      requirements for heparin/HS interactions with VEGF receptor (VEGFR)-1, NRP-1, and
      VEGF165 in complex with VEGFR-2 and NRP-1. We demonstrate that these structural
      requirements are distinct for each interaction. We further show that VEGF165,
      VEGFR-2, and monomeric NRP-1 bind weakly to heparin alone yet show synergistic
      binding to heparin when presented together in various combinations. This
      synergistic binding appears to translate to alterations in VEGF signaling in
      endothelial cells. We found that soluble NRP-1 increases VEGF binding and
      activation of VEGFR-2 and ERK1/2 in endothelial cells and that these effects
      require sulfated HS. These data suggest that the presence of HS/heparin and NRP-1
      may dictate the specific receptor type activated by VEGF and ultimately determine
      the biological output of the system. The ability of co-receptors to fine-tune
      VEGF responsiveness suggests the possibility that VEGF-mediated angiogenesis can
      be selectively stimulated or inhibited by targeting HS/heparin and NRP-1. 

PMID- 25979343
TI  - Probing the Solution Structure of IkappaB Kinase (IKK) Subunit gamma and Its
      Interaction with Kaposi Sarcoma-associated Herpes Virus Flice-interacting Protein
      and IKK Subunit beta by EPR Spectroscopy.
AB  - Viral flice-interacting protein (vFLIP), encoded by the oncogenic Kaposi sarcoma
      associated herpes virus (KSHV), constitutively activates the canonical nuclear
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) pathway. This
      is achieved through subversion of the IkappaB kinase (IKK) complex (or
      signalosome), which involves a physical interaction between vFLIP and the
      modulatory subunit IKKgamma. Although this interaction has been examined both in
      vivo and in vitro, the mechanism by which vFLIP activates the kinase remains to
      be determined. Because IKKgamma functions as a scaffold, recruiting both vFLIP
      and the IKKalpha/beta subunits, it has been proposed that binding of vFLIP could
      trigger a structural rearrangement in IKKgamma conducive to activation. To
      investigate this hypothesis we engineered a series of mutants along the length of
      the IKKgamma molecule that could be individually modified with nitroxide spin
      labels. Subsequent distance measurements using electron paramagnetic resonance
      spectroscopy combined with molecular modeling and molecular dynamics simulations
      revealed that IKKgamma is a parallel coiled-coil whose response to binding of
      vFLIP or IKKbeta is localized twisting/stiffening and not large-scale
      rearrangements. The coiled-coil comprises N- and C-terminal regions with distinct
      registers accommodated by a twist: this structural motif is exploited by vFLIP,
      allowing it to bind and subsequently activate the NF-kappaB pathway. In vivo
      assays confirm that NF-kappaB activation by vFLIP only requires the N-terminal
      region up to the transition between the registers, which is located directly C
      terminal of the vFLIP binding site. 

PMID- 25979344
TI  - Unique Features of Human Protein Arginine Methyltransferase 9 (PRMT9) and Its
      Substrate RNA Splicing Factor SF3B2.
AB  - Human protein arginine methyltransferase (PRMT) 9 symmetrically dimethylates
      arginine residues on splicing factor SF3B2 (SAP145) and has been functionally
      linked to the regulation of alternative splicing of pre-mRNA. Site-directed
      mutagenesis studies on this enzyme and its substrate had revealed essential
      unique residues in the double E loop and the importance of the C-terminal
      duplicated methyltransferase domain. In contrast to what had been observed with
      other PRMTs and their physiological substrates, a peptide containing the
      methylatable Arg-508 of SF3B2 was not recognized by PRMT9 in vitro. Although
      amino acid substitutions of residues surrounding Arg-508 had no great effect on
      PRMT9 recognition of SF3B2, moving the arginine residue within this sequence
      abolished methylation. PRMT9 and PRMT5 are the only known mammalian enzymes
      capable of forming symmetric dimethylarginine (SDMA) residues as type II PRMTs.
      We demonstrate here that the specificity of these enzymes for their substrates is
      distinct and not redundant. The loss of PRMT5 activity in mouse embryo
      fibroblasts results in almost complete loss of SDMA, suggesting that PRMT5 is the
      primary SDMA-forming enzyme in these cells. PRMT9, with its duplicated
      methyltransferase domain and conserved sequence in the double E loop, appears to
      have a unique structure and specificity among PRMTs for methylating SF3B2 and
      potentially other polypeptides. 

PMID- 25979345
TI  - Porphyromonas gingivalis-derived RgpA-Kgp Complex Activates the Macrophage
      Urokinase Plasminogen Activator System: IMPLICATIONS FOR PERIODONTITIS.
AB  - Urokinase plasminogen activator (uPA) converts plasminogen to plasmin, resulting
      in a proteolytic cascade that has been implicated in tissue destruction during
      inflammation. Periodontitis is a highly prevalent chronic inflammatory disease
      characterized by destruction of the tissue and bone that support the teeth. We
      demonstrate that stimulation of macrophages with the arginine- and lysine
      specific cysteine protease complex (RgpA-Kgp complex), produced by the keystone
      pathogen Porphyromonas gingivalis, dramatically increased their ability to
      degrade matrix in a uPA-dependent manner. We show that the RgpA-Kgp complex
      cleaves the inactive zymogens, pro-uPA (at consensus sites Lys(158)-Ile(159) and
      Lys(135)-Lys(136)) and plasminogen, yielding active uPA and plasmin,
      respectively. These findings are consistent with activation of the uPA
      proteolytic cascade by P. gingivalis being required for the pathogen to induce
      alveolar bone loss in a model of periodontitis and reveal a new host-pathogen
      interaction in which P. gingivalis activates a critical host proteolytic pathway
      to promote tissue destruction and pathogen virulence. 

PMID- 25979347
TI  - Formaldehyde cross-linking and structural proteomics: Bridging the gap.
AB  - Proteins are dynamic entities constantly moving and altering their structures
      based on their functions and interactions inside and outside the cell.
      Formaldehyde cross-linking combined with mass spectrometry can accurately capture
      interactions of these rapidly changing biomolecules while maintaining their
      physiological surroundings. Even with its numerous established uses in biology
      and compatibility with mass spectrometry, formaldehyde has not yet been applied
      in structural proteomics. However, formaldehyde cross-linking is moving toward
      analyzing tertiary structure, which conventional cross-linkers have already
      accomplished. The purpose of this review is to describe the potential of
      formaldehyde cross-linking in structural proteomics by highlighting its
      applications, characteristics and current status in the field. 

PMID- 25979346
TI  - Methods for discovery and characterization of cell subsets in high dimensional
      mass cytometry data.
AB  - The flood of high-dimensional data resulting from mass cytometry experiments that
      measure more than 40 features of individual cells has stimulated creation of new
      single cell computational biology tools. These tools draw on advances in the
      field of machine learning to capture multi-parametric relationships and reveal
      cells that are easily overlooked in traditional analysis. Here, we introduce a
      workflow for high dimensional mass cytometry data that emphasizes unsupervised
      approaches and visualizes data in both single cell and population level views.
      This workflow includes three central components that are common across mass
      cytometry analysis approaches: (1) distinguishing initial populations, (2)
      revealing cell subsets, and (3) characterizing subset features. In the
      implementation described here, viSNE, SPADE, and heatmaps were used sequentially
      to comprehensively characterize and compare healthy and malignant human tissue
      samples. The use of multiple methods helps provide a comprehensive view of
      results, and the largely unsupervised workflow facilitates automation and helps
      researchers avoid missing cell populations with unusual or unexpected phenotypes.
      Together, these methods develop a framework for future machine learning of cell
      identity. 

PMID- 25979348
TI  - Self-reported Medication Adherence and Adverse Patient Safety Events in CKD.
AB  - BACKGROUND: Promoting medication adherence is a recognized challenge for
      prescribers. In this study, we examine whether lower medication adherence is
      associated with adverse safety events in individuals with decreased estimated
      glomerular filtration rates (eGFRs). STUDY DESIGN: Cross-sectional baseline
      analysis of prospective cohort. SETTING & PARTICIPANTS: Baseline analysis of the
      Safe Kidney Care (SKC) Cohort Study, a prospective study of individuals with
      eGFRs<60 mL/min/1.73 m(2) intended to assess the incidence of disease-specific
      safety events. Kidney transplant recipients were excluded. PREDICTOR: Self
      reported medication adherence based on responses to 3 questions ascertaining
      degree of medication regimen adherence. OUTCOMES: Adverse safety events were self
      reported at baseline (class I events), such as hypoglycemia or fall thought to be
      related to a medication, or detected incidentally during the baseline visit
      (class II events), for example, hypotension or hyperkalemia. Potential drug
      related problems (DRPs) were determined by analyzing participants' medications
      with respect to dosing guidelines based on their screening eGFRs at the time of
      medication reporting. MEASUREMENTS: Relationship between medication adherence and
      disease-specific patient safety events. RESULTS: Of 293 SKC participants, 154
      (53%) were classified as having lower medication adherence. After multivariable
      adjustment, lower medication adherence was significantly associated with a class
      I or II safety event (prevalence ratio [PR], 1.21; 95% CI, 1.04-1.41) and
      potential DRPs (PR, 1.29; 95% CI, 1.02-1.63). Lower medication adherence was also
      significantly associated with multiple (>=2) class I events (PR, 1.71; 95% CI,
      1.18-2.49), multiple class I or II events (PR, 1.35; 95% CI, 1.04-1.76), and
      multiple potential DRPs (PR, 2.11; 95% CI, 1.08-2.69) compared with those with
      higher medication adherence. LIMITATIONS: Use of self-reported medication
      adherence rather than pharmacy records. Clinical relevance of detected safety
      events is unclear. CONCLUSIONS: Lower medication adherence is associated with
      adverse safety events in individuals with eGFRs<60 mL/min/1.73 m(2).

PMID- 25979350
TI  - Setting up of ambulatory hysteroscopy service.
AB  - There is an obvious trend towards developing ambulatory procedures in gynaecology
      with ambulatory hysteroscopy as its mainstay. In the recent years, the fast pace
      of modern technological advances in gynaecologic endoscopy, and particularly in
      the field of hysteroscopy, have been both thrilling and spectacular. Despite
      this, the uptake of operative hysteroscopy in ambulatory settings has been
      relatively slow. There is some apprehension amongst gynaecologists to embark on
      therapeutic outpatient hysteroscopy, and an organisational change is required to
      alter the mindset. Although there are best practice guidelines for outpatient
      hysteroscopy, there are unresolved issues around adequate training and
      accreditation of future hysteroscopists. Virtual-reality simulation training for
      operative hysteroscopy has shown promising preliminary results, and it is being
      aggressively evaluated and validated. This review article is an attempt to
      provide a useful practical guide to all those who wish to implement ambulatory
      hysteroscopy services in their outpatient departments. 

PMID- 25979349
TI  - Denosumab for low bone mass in hemodialysis patients: a noncontrolled trial.

PMID- 25979351
TI  - Team training for safer birth.
AB  - Effective and coordinated teamworking is key to achieving safe birth for mothers
      and babies. Confidential enquiries have repeatedly identified deficiencies in
      teamwork as factors contributing to poor maternal and neonatal outcomes. The
      ingredients of a successful multi-professional team are varied, but research has
      identified some fundamental teamwork behaviours, with good communication,
      proficient leadership and situational awareness at the heart. Simple, evidence
      based methods in teamwork training can be seamlessly integrated into a core,
      mandatory obstetric emergency training. Training should be an enjoyable,
      inclusive and beneficial experience for members of staff. Training in teamwork
      can lead to improved clinical outcomes and better birth experience for women. 

PMID- 25979352
TI  - Restoring Isometry in Lateral Ulnar Collateral Ligament Reconstruction.
AB  - PURPOSE: To ascertain whether placing the humeral attachment of the lateral ulnar
      collateral ligament (LUCL) at the humeral center of rotation (hCOR) on the
      humerus would provide the most isometric reconstruction. METHODS: We analyzed 13
      cadaver limbs from mid-humerus to the hand. The morphology of the ligament
      complex was assessed. The hCOR was then found using radiographic parameters. We
      chose 7 points on the humerus located at and around the hCOR and 3 points
      paralleling the supinator crest of the ulna and then calculated distances from
      these points using a digital caliper at 0 degrees , 30 degrees , 60 degrees , 90
      degrees , and 130 degrees  flexion. Differences in potential ligamentous lengths
      (termed graft elongation) were then calculated and statistical analysis was
      performed. RESULTS: There was no perfectly isometric point along the humerus or
      ulna. However, in all specimens the hCOR was the most isometric point for the
      humeral reconstruction site, with an average graft elongation of 1.1 mm.
      Differences in humeral tunnel position dramatically affected graft elongation at
      all 3 ulnar insertions. Overall, ulnar position had a minimal effect on graft
      elongation. CONCLUSIONS: Although no perfectly isometric points were found, the
      humeral center of rotation consistently reproduced the most isometry when
      assessing graft elongation over range of motion. These data may assist surgeons
      in proper tunnel placement in LUCL reconstruction. CLINICAL RELEVANCE: In LUCL
      reconstruction, the humeral tunnel should be placed as close as possible to the
      center of rotation, whereas placement on the ulna is less critical.

PMID- 25979353
TI  - Continuous monitoring of highly reactive oxygen radicals during in vivo
      microdialysis.
AB  - BACKGROUND: Terephthalate (TA(2-)), which reacts with highly reactive oxygen
      species (hROS) to form the fluorophor 2-hydroxy terephthalic acid (OH-TA) with a
      high selectivity, has been used for determining hROS formation during in vivo
      microdialysis. Previously this involved collecting fractions of the
      microdialysate and determining the OH-TA formed after HPLC (the batch method).
      NEW METHOD: This work reports the development and validation of a procedure for
      continuously determining hROS formation during microdialysis. TA(2-) was added to
      the artificial cerebrospinal fluid (aCSF) perfusing medium to trap hROS. OH-TA
      formation was detected in real time with a sensitive fluorescence detector
      equipped with a capillary flow cell that was coupled directly to the effluent
      stream of the microdialysis system. RESULTS: The behaviour of the system was
      assessed by comparison with the batch method and using a well-characterized
      animal model of excitotoxic damage, based on the application of high
      concentrations (1mM and 500MUM) of the non-NMDA glutamate receptor agonist
      kainate (KA) to the neostriatum. Data for the evoked release of taurine were also
      determined in these samples. No temporal difference between hROS and taurine
      release could be detected. COMPARISON WITH EXISTING METHOD(S): The flow method
      had a comparable sensitivity of hROS detection to the batch method. It was
      simpler, cheaper and less time-consuming than the batch method. CONCLUSIONS: This
      direct system is convenient and technically undemanding. It should be useful for
      the rapid assessment of the hROS responses to neurotoxins and other compounds in
      microdialysis experiments in vivo.

PMID- 25979356
TI  - Abstracts of the UK-Russia Researcher Links Workshop: Extracellular vesicles -
      mechanisms of biogenesis and roles in disease pathogenesis.

PMID- 25979355
TI  - UK-Russia Researcher Links Workshop: extracellular vesicles - mechanisms of
      biogenesis and roles in disease pathogenesis, M.V. Lomonosov Moscow State
      University, Moscow, Russia, 1-5 March 2015.

PMID- 25979357
TI  - Parkin-mediated responses against infection and wound involve TSPO-VDAC complex
      in Drosophila.
AB  - Parkin, an E3 ubuquitin ligase associated with Parkinson's disease (PD), has
      recently been implicated in mediating innate immunity. However, molecular details
      regarding parkin-mediated immune response remain to be elucidated. Here, we
      identified mitochondrial TSPO-VDAC complex to genetically interact with parkin in
      mediating responses against infection and wound in Drosophila. The loss-of
      function mutation in parkin results in defective immune response against
      bacterial infection. Additionally, parkin mutant larvae showed hypersensitivity
      against wound regardless of bacterial infection. Interestingly, the combinatorial
      trans-heterozygotic mutations in parkin and TSPO, or parkin and VDAC showed
      similar lethal tendency with parkin homozygous mutants. Furthermore, knockdown of
      TSPO alone also resulted in defective responses to infection and wound
      analogously to parkin mutants. Taken together, we propose that parkin cooperates
      with TSPO-VDAC complex to mediate responses against infection and wound. 

PMID- 25979358
TI  - Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-kappaB
      p65 subunit nuclear import.
AB  - Constitutive NF-kappaB activation is required for survival of activated B cell
      like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF
      kappaB targeting strategies lack cancer cell specificity. Here, we identified a
      novel inhibitor, piperlongumine, features direct binding to NF-kappaB p65 subunit
      and suppression of p65 nuclear import. This was accompanied by NF-kappaB reporter
      activity suppression and NF-kappaB target gene downregulation. Moreover, mutation
      of Cys(38) to Ser in p65 abolished this effect of piperlongumine on inhibition of
      p65 nuclear import. Furthermore, we show that piperlongumine selectively
      inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably,
      it has been reported that piperlongumine did not affect normal cells even at high
      doses and was nontoxic to animals. Hence, our current study provides new insight
      into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target
      therapy. 

PMID- 25979359
TI  - SIRT1 deacetylates and stabilizes hypoxia-inducible factor-1alpha (HIF-1alpha)
      via direct interactions during hypoxia.
AB  - Upon shift to a hypoxic environment, cellular HIF-1alpha protein is stabilized,
      with a rapid decline in oxygen-sensitive hydroxylation. Several additional post
      translational modifications of HIF-1alpha are critical in controlling protein
      stability during hypoxia. In the present study, we showed that SIRT1 stabilizes
      HIF-1alpha via direct binding and deacetylation during hypoxia. SIRT1 depletion
      or inactivation led to reduced hypoxic HIF-1alpha accumulation, accompanied by an
      increase in HIF-1alpha acetylation. Impaired HIF-1alpha accumulation was
      recovered upon inhibition of 26S proteasome activity, indicating that SIRT1 is
      essential for HIF-1alpha stabilization during hypoxia. Consistently, HIF-1alpha
      accumulation was enhanced upon overexpression of wild-type SIRT1, but not its
      dominant-negative form. SIRT1-mediated accumulation of HIF-1alpha protein led to
      increased expression of HIF-1alpha target genes, including VEGF, GLUT1 and MMP2,
      and ultimate promotion of cancer cell invasion. These findings collectively imply
      that hypoxic HIF-1alpha stabilization requires SIRT1 activation. Furthermore,
      SIRT1 protection of HIF-1alpha from acetylation may be a prerequisite for
      stabilization and consequent enhancement of cell invasion. 

PMID- 25979360
TI  - Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by
      reduction of iPLA(2) activity.
AB  - Caspase-independent, non-apoptotic cell death is an important therapeutic target
      in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit
      cytoprotective effects on the ischemic heart, but the mechanisms are poorly
      understood. In this research, we found that pretreatment of leptin strongly
      suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on
      cardiomyocytes. Leptin was also shown to significantly inhibit the activity of
      iPLA2, which is considered to play crucial roles in non-apoptotic cell death,
      resulting in effective prevention of ischemia-induced myocyte death. These
      findings provide the first evidence of a protective mechanism of leptin against
      ischemia-induced non-apoptotic cardiomyocyte death. 

PMID- 25979361
TI  - Xenopus Claudin-6 is required for embryonic pronephros morphogenesis and terminal
      differentiation.
AB  - Claudins are tetratransmembrane tight junction proteins and play important roles
      in regulating paracellular permeability of different nephron segments of the
      kidney. However, the roles of claudins in kidney development remain largely
      unknown. Here we studied the expression and functions of claudin-6 in Xenopus
      pronephros development. Xenopus claudin-6 is expressed in the developing
      pronephric tubule and duct but not glomus. Knockdown of claudin-6 by specific
      morpholino led to severe defects in pronephros tubular morphogenesis and blocked
      the terminal differentiation of the tubule cells. The claudin-6 morpholino
      targeted tubule cells showed failure of apical accumulation of actin and reduced
      lateral expression of tight junction protein Na/K-ATPase, suggesting an
      incomplete epithelization likely due to defected cell adhesions and apical
      lateral polarity. Our work uncovered a novel role for claudin-6 in embryonic
      kidney development. 

PMID- 25979362
TI  - Medical Students' Death Anxiety: Severity and Association With Psychological
      Health and Attitudes Toward Palliative Care.
AB  - CONTEXT: Death anxiety (DA) is related to awareness of the reality of dying and
      death and can be negatively related to a person's psychological health.
      Physicians' DA also may influence their care for patients approaching death.
      Doctors face death in a professional context for the first time at medical
      school, but knowledge about DA among medical students is limited. OBJECTIVES:
      This study examined medical students' DA in relation to: 1) its severity, gender
      differences, and trajectory during medical education and 2) its associations with
      students' attitudes toward palliative care and their psychological health.
      METHODS: Four cohorts of core science and four cohorts of clinical students at
      the University of Cambridge Medical School took part in a questionnaire survey
      with longitudinal follow-up. Students who provided data on the revised Collett
      Lester Fear of Death Scale were included in the analysis (n = 790). RESULTS:
      Medical students' DA was moderate, with no gender differences and remained very
      stable over time. High DA was associated with higher depression and anxiety
      levels and greater concerns about the personal impact of providing palliative
      care. CONCLUSION: The associations between high DA and lower psychological health
      and negative attitudes toward palliative care are concerning. It is important to
      address DA during medical education to enhance student's psychological health and
      the quality of their future palliative care provision.

PMID- 25979363
TI  - Balancing risks and benefits of bariatric surgery for type 2 diabetes.

PMID- 25979365
TI  - Controlled trials: allocation concealment, random allocation, and blinding.

PMID- 25979364
TI  - Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year
      outcomes of a 5-year, randomised, controlled trial.
AB  - BACKGROUND: Conventional treatments for patients with type 2 diabetes are often
      inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2
      years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical
      management. METHODS: We report 2-year outcomes of a 5-year randomised trial (the
      Diabetes Surgery Study) at four teaching hospitals (three in the USA and one in
      Taiwan). At baseline, eligible participants had to have HbA1c of at least 8.0%
      (64 mmol/mol), BMI between 30.0 and 39.9 kg/m(2), and type 2 diabetes for at
      least 6 months, and be aged 30-67 years. We randomly assigned participants to
      receive either intensive lifestyle and medical management alone (lifestyle and
      medical management), or lifestyle and medical management plus standard Roux-en-Y
      gastric bypass surgery (gastric bypass). Staff from the clinical centres had
      access to data from individual patients, but were masked to other patients' data
      and aggregated data until the 2-year follow-up. Drugs for hyperglycaemia,
      hypertension, and dyslipidaemia were prescribed by protocol. The primary endpoint
      was achievement of the composite treatment goal of HbA1c less than 7.0% (53
      mmol/mol), LDL cholesterol less than 2.59 mmol/L, and systolic blood pressure
      less than 130 mm Hg at 12 months; here we report the composite outcome and other
      pre-planned secondary outcomes at 24 months. Analyses were done on an intention
      to-treat basis, with multiple imputations for missing data. This study is
      registered with ClinicalTrials.gov, number NCT00641251, and is still ongoing.
      FINDINGS: Between April 21, 2008, and Nov 21, 2011, we randomly assigned 120
      eligible patients to either lifestyle and medical management alone (n=60) or with
      the addition of gastric bypass (n=60). One patient in the lifestyle and medical
      management group died (from pancreatic cancer), thus 119 were included in the
      primary analysis. Significantly more participants in the gastric bypass group
      achieved the composite triple endpoint at 24 months than in the lifestyle and
      medical management group (26 [43%] vs eight [14%]; odds ratio 5.1 [95% CI 2.0
      12.6], p=0.0004), mainly through improved glycaemic control (HbA1c <7.0% [53
      mmol/mol] in 45 [75%] vs 14 [24%]; treatment difference -1.9% (-2.5 to -1.4);
      p=0.0001). 46 clinically important adverse events occurred in the gastric bypass
      group and 25 in the lifestyle and medical management group (mainly infections in
      both groups [four in the lifestyle and medical management group, eight in the
      gastric bypass group]). With a negative binomial model adjusted for site, the
      event rate for the gastric bypass group was non-significantly higher than the
      lifestyle and medical management group by a factor of 1.67 (95% CI 0.98-2.87,
      p=0.06). Across both years of the study, the gastric bypass group had seven
      serious falls with five fractures, compared with three serious falls and one
      fracture in the lifestyle and medical management group. All fractures happened in
      women. Many more nutritional deficiencies occurred in the gastric bypass group
      (mainly deficiencies in iron, albumin, calcium, and vitamin D), despite protocol
      use of nutritional supplements. INTERPRETATION: The addition of gastric bypass to
      lifestyle and medical management in patients with type 2 diabetes improved
      diabetes control, but adverse events and nutritional deficiencies were more
      frequent. Larger and longer studies are needed to investigate whether the
      benefits and risk of gastric bypass for type 2 diabetes can be balanced. FUNDING:
      Covidien, National Institutes of Health, National Institute of Diabetes and
      Digestive and Kidney Diseases Nutrition Obesity Research Centers, and the
      National Center for Advancing Translational Sciences.

PMID- 25979366
TI  - Mossy fiber mis-pathfinding and semaphorin reduction in the hippocampus of alpha
      CaMKII hKO mice.
AB  - Recent evidence indicates that alpha-isoform of calcium/calmodulin-dependent
      protein kinase II (alpha-CaMKII) deficiency in adult mice induces phenotypic
      immaturity of dentate granule cells, defined by dendritic disturbance and
      aberrant maturational neuron marker expression. Mice possessing a heterozygous
      inactivation of alpha-CaMKII display abnormal behavioral phenotypes, including
      working memory deficits similar to those observed in psychiatric patients.
      Currently, how the guidance of mossy fibers, the axonal projections of granule
      cells, are topologically regulated in the dentate gyrus of alpha-CaMKII deficient
      animals is not well understood, even though axonal morphogenesis is a key factor
      for modulating neuronal transmission and animal behavior. In the present study,
      we explored the involvement of semaphorin signaling, a well-studied guidance
      factor in mossy fiber pathfinding, in alpha-CaMKII heterozygous knock-out mice
      (alpha-CaMKII hKO mice). Using immunohistochemical characterization, we found
      mossy fibers invade not only the CA3 stratum lucidum region, but also stratum
      oriens region where mossy fibers do not usually bundle. Furthermore, alpha-CaMKII
      hKO mice have decreased semaphorin-3A expression. These results suggest mossy
      fiber mis-guidance, possibly regulated by semaphorin-3A, is one of the biomarkers
      reflecting immaturity in dentate granule cells, possibly contributing to abnormal
      behavioral phenotypes.

PMID- 25979367
TI  - Is there a role for screening asymptomatic patients with diabetes?
AB  - Coronary artery disease (CAD) remains a leading cause of death among patients
      with diabetes mellitus. However, many patients with diabetes and CAD are
      asymptomatic and may sustain a myocardial infarction as their presenting symptom
      of CAD. Non-invasive cardiovascular imaging offers an opportunity to detect the
      presence and severity of CAD, or its hemodynamic consequences. The Detection of
      Ischemia in Asymptomatic Diabetics study and the FACTOR-64 study examined the
      utility of non-invasive imaging tests to evaluate asymptomatic individuals with
      diabetes mellitus. The results of these trials may have been negative with regard
      to promoting CAD screening of asymptomatic diabetic patients, but they do
      strengthen the position of optimal medical management in reducing cardiovascular
      events. However, performing a trial to include true high-risk patients who have
      CAD and are more likely to have silent ischemia could lead to prognostically
      beneficial coronary revascularizations. 

PMID- 25979368
TI  - Curcumin potentiates the anti-leukemia effects of imatinib by downregulation of
      the AKT/mTOR pathway and BCR/ABL gene expression in Ph+ acute lymphoblastic
      leukemia.
AB  - Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is
      triggered by BCR/ABL and SRC family tyrosine kinases. They interact with each
      other and subsequently activate downstream growth-signaling pathways, including
      Raf/MEK/ERK, Akt/mTOR, and STAT5 pathways. Although imatinib is the standard
      treatment for Ph+ leukemia, response rate of Ph+ ALL to imatinib is low, relapse
      is frequent and quick. Studies have documented the potential anti-tumor
      activities of curcumin. However, whether curcumin can be used in the therapy for
      Ph+ ALL remains obscure. Here, we reported that curcumin induced apoptosis by
      inhibition of AKT/mTOR and ABL/STAT5 signaling, down-regulation of BCR/ABL
      expression, and induction of the BCL2/BAX imbalance. Curcumin exerted synergetic
      anti-leukemia effects with imatinib by inhibition of the imatinib-mediated
      overactivation of AKT/mTOR signaling and down-regulation of BCR/ABL gene
      expression. In primary samples from Ph+ ALL patients, curcumin inhibited cellular
      proliferation and down-regulated constitutive activation of growth-signaling
      pathways not only in newly diagnosed patients but also in imatinib-resistant
      patients. In Ph+ ALL mouse models, curcumin exhibited synergetic anti-leukemia
      effects with imatinib. These results demonstrated that curcumin might be a
      promising agent for Ph+ ALL patients. 

PMID- 25979354
TI  - Biological properties of extracellular vesicles and their physiological
      functions.
AB  - In the past decade, extracellular vesicles (EVs) have been recognized as potent
      vehicles of intercellular communication, both in prokaryotes and eukaryotes. This
      is due to their capacity to transfer proteins, lipids and nucleic acids, thereby
      influencing various physiological and pathological functions of both recipient
      and parent cells. While intensive investigation has targeted the role of EVs in
      different pathological processes, for example, in cancer and autoimmune diseases,
      the EV-mediated maintenance of homeostasis and the regulation of physiological
      functions have remained less explored. Here, we provide a comprehensive overview
      of the current understanding of the physiological roles of EVs, which has been
      written by crowd-sourcing, drawing on the unique EV expertise of academia-based
      scientists, clinicians and industry based in 27 European countries, the United
      States and Australia. This review is intended to be of relevance to both
      researchers already working on EV biology and to newcomers who will encounter
      this universal cell biological system. Therefore, here we address the molecular
      contents and functions of EVs in various tissues and body fluids from cell
      systems to organs. We also review the physiological mechanisms of EVs in
      bacteria, lower eukaryotes and plants to highlight the functional uniformity of
      this emerging communication system. 

PMID- 25979370
TI  - MicroRNAs mediated targeting on the Yin-yang dynamics of DNA methylation in
      disease and development.
AB  - For decades, DNA methylation at the 5 position of cytosine (5mC) catalyzed by DNA
      methyltransferases (DNMTs) is a well-known epigenetic modification in mammalian
      genome, where it modulates chromatin remodeling and transcriptional silencing.
      The discovery of Ten-eleven translocation (TET) enzymes that oxidize 5mC to 5
      hydroxymethylcytosine (5hmC) prompts a new era of DNA demethylation research. It
      is now established that in DNA demethylation pathway 5mC is first converted to 5
      hydroxymethylcytosine (5hmC), then 5-formylcytosine (5fC) and 5-carboxylcytosine
      (5caC) through TETs. Conversion to unmethylated cytosine (5C) is further
      facilitated by excision mechanism through thymine-DNA glycosylase (TDG) or base
      excision repair (BER) pathway. Our understanding of DNMTs and TETs on epigenetic
      dynamics of cytosine methylation has led to a completion of the methylation (Yin)
      - demethylation (Yang) cycle on epigenetic modifications on cytosine. However,
      the regulations on DNA demethylation pathway remain largely unknown. In this
      review, we provide the recent advances on epigenetic dynamics of DNA
      demethylation and its potential control from the prespective of small non-coding
      RNA-mediated regulation. Specifically, we will illustrate how microRNAs
      contribute to active DNA demethylation control in normal and disease development
      based on recent findings in stem cells and cancer. This article is part of a
      Directed Issue entitled: Epigenetics dynamics in development and disease. 

PMID- 25979369
TI  - The role of epigenetics in the endothelial cell shear stress response and
      atherosclerosis.
AB  - Currently in the field of vascular biology, the role of epigenetics in
      endothelial cell biology and vascular disease has attracted more in-depth study.
      Using both in vitro and in vivo models of blood flow, investigators have recently
      begun to reveal the underlying epigenetic regulation of endothelial gene
      expression. Recently, our group, along with two other independent groups, have
      demonstrated that blood flow controls endothelial gene expression by DNA
      methyltransferases (DNMT1 and 3A). Disturbed flow (d-flow), characterized by low
      and oscillating shear stress (OS), is pro-atherogenic and induces expression of
      DNMT1 both in vivo and in vitro. D-flow regulates genome-wide DNA methylation
      patterns in a DNMT-dependent manner. The DNMT inhibitor 5-Aza-2'deoxycytidine
      (5Aza) or DNMT1 siRNA reduces OS-induced endothelial inflammation. Moreover, 5Aza
      inhibits the development of atherosclerosis in ApoE(-/-) mice. Through a systems
      biological analysis of genome-wide DNA methylation patterns and gene expression
      data, we found 11 mechanosensitive genes which were suppressed by d-flow in vivo,
      experienced hypermethylation in their promoter region in response to d-flow, and
      were rescued by 5Aza treatment. Interestingly, among these mechanosensitive
      genes, the two transcription factors HoxA5 and Klf3 contain cAMP-response
      elements (CRE), which may indicate that methylation of CRE sites could serve as a
      mechanosensitive master switch in gene expression. These findings provide new
      insight into the mechanism by which flow controls epigenetic DNA methylation
      patterns, which in turn alters endothelial gene expression, regulates vascular
      biology, and induces atherosclerosis. These novel findings have broad
      implications for understanding the biochemical mechanisms of atherogenesis and
      provide a basis for identifying potential therapeutic targets for
      atherosclerosis. This article is part of a Directed Issue entitled: Epigenetics
      dynamics in development and disease. 

PMID- 25979371
TI  - A paradox of cumulative culture.
AB  - Culture can grow cumulatively if socially learnt behaviors are improved by
      individual learning before being passed on to the next generation. Previous
      authors showed that this kind of learning strategy is unlikely to be
      evolutionarily stable in the presence of a trade-off between learning and
      reproduction. This is because culture is a public good that is freely exploited
      by any member of the population in their model (cultural social dilemma). In this
      paper, we investigate the effect of vertical transmission (transmission from
      parents to offspring), which decreases the publicness of culture, on the
      evolution of cumulative culture in both infinite and finite population models. In
      the infinite population model, we confirm that culture accumulates largely as
      long as transmission is purely vertical. It turns out, however, that introduction
      of even slight oblique transmission drastically reduces the equilibrium level of
      culture. Even more surprisingly, if the population size is finite, culture hardly
      accumulates even under purely vertical transmission. This occurs because
      stochastic extinction due to random genetic drift prevents a learning strategy
      from accumulating enough culture. Overall, our theoretical results suggest that
      introducing vertical transmission alone does not really help solve the cultural
      social dilemma problem. 

PMID- 25979372
TI  - Computational analysis of AnmK-like kinase: New insights into the cell wall
      metabolism of fungi.
AB  - 1,6-Anhydro-N-acetylmuramic acid kinase (AnmK) is the unique enzyme that marks
      the recycling of the cell wall of Escherichia coli. Here, 81 fungal AnmK-like
      kinase sequences from 57 fungal species were searched in the NCBI database and a
      phylogenetic tree was constructed. The three-dimensional structure of an AnmK
      like kinase, levoglucosan kinase (LGK) of the yeast Lipomyces starkeyi, was
      modeled; molecular docking revealed that AnmK and LGK are conserved proteins, and
      187Asp, 212Asp are enzymatic residues, respectively. Analysis suggests that 1,6
      anhydro-N-acetylglucosamine (anhGlcNAc) and/or 1,6-anhydro-beta-d-glucosamine
      (anhGlcN) would be the appropriate substrates of AnmK-like kinases. Also, the
      counterparts of other characteristic enzymes of cell wall recycling of bacteria
      were found in fungi. Taken together, it is proposed that a putative recycling of
      anhGlcNAc/anhGlcN, which is associated with the hydrolysis of cell walls, exists
      in fungi. This computational analysis will provide new insights into the
      metabolism of fungal cell walls. 

PMID- 25979374
TI  - Airborne exposure to inhalable hexavalent chromium in welders and other
      occupations: Estimates from the German MEGA database.
AB  - This study aimed to estimate occupational exposure to inhalable hexavalent
      chromium (Cr(VI)) using the exposure database MEGA. The database has been
      compiling Cr(VI) concentrations and ancillary data about measurements at German
      workplaces. We analysed 3659 personal measurements of inhalable Cr(VI) collected
      between 1994 and 2009. Cr(VI) was determined spectrophotometrically at 540 nm
      after reaction with diphenylcarbazide. We assigned the measurements to pre
      defined at-risk occupations using the information provided about the workplaces.
      Two-thirds of the measurements were below the limit of quantification (LOQ) and
      multiply imputed according to the distribution above LOQ. The 75th percentile
      value was 5.2 MUg/m(3) and the 95th percentile was 57.2 MUg/m(3). We predicted
      the geometric mean for 2h sampling in the year 2000, and the time trend of Cr(VI)
      exposure in these settings with and without adjustment for the duration of
      measurements. The largest dataset was available for welding (N = 1898), which
      could be further detailed according to technique. The geometric means were above
      5 MUg/m(3) in the following situations: spray painting, shielded metal arc
      welding, and flux-cored arc welding if applied to stainless steel. The geometric
      means were between 1 MUg/m(3) and 5 MUg/m(3) for gas metal arc welding of
      stainless steel, cutting, hard-chromium plating, metal spraying and in the
      chemical chromium industry. The exposure profiles described here are useful for
      epidemiologic and industrial health purposes. Exposure to Cr(VI) varies not only
      between occupations, but also within occupations as shown for welders. In
      epidemiologic studies, it would be desirable to collect exposure-specific
      information in addition to the job title.

PMID- 25979373
TI  - Clinical versus laboratory screening for sexually transmitted infections prior to
      insertion of intrauterine contraception among women living with HIV/AIDS: a
      randomized controlled trial.
AB  - STUDY QUESTION: Does laboratory testing after syndromic screening for sexually
      transmitted infections (STIs) reduce the rate of intrauterine contraception (IUC)
      removal among women living with HIV/AIDS (WLHA)? SUMMARY ANSWER: Additional
      laboratory testing after syndromic screening for STIs did not affect the
      likelihood that a woman would remove an IUC immediately or within 1 year of IUC
      use or the frequency of post-insertion unscheduled clinic visits. In low-risk
      WLHA, the incidence rate of IUC removal is low with or without laboratory
      testing. WHAT IS KNOWN ALREADY: Fear of infectious morbidity remains an obstacle
      to uptake of IUC by WLHA. The value of laboratory testing after syndromic
      screening for STI before the insertion of IUC remains uncertain. STUDY DESIGN,
      SIZE, DURATION: We enrolled WLHA from 2 September to 6 December 2013 and followed
      them up to 31 December 2014. After syndromic screening, 703 women free of STIs
      were randomized to either additional laboratory screening or no additional
      screening for STI before IUC insertion. The randomization sequence was generated
      by an independent statistician and randomization numbers placed in opaque
      sequentially numbered sealed envelopes. All women randomized had an IUC inserted
      and in all 672 participants completed the 1-year follow-up. The study staff who
      followed up the participants were blinded to the study allocation groups.
      Incidence rate ratios (IRRs) were used to compare the incidence rates of IUC
      removal, unscheduled clinic attendance and IUC continuation between the two
      groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women eligible to participate
      were 18-49 years old at study entry, in a relationship with a male partner,
      wanted to avoid pregnancy for at least 1 year and were undergoing HIV/AIDS care
      at Mulago Hospital, Uganda. Participants completed a baseline questionnaire and
      up to four follow-up questionnaires until discontinuation of IUC, loss to follow
      up or end of study observation after 12 months. MAIN RESULTS AND THE ROLE OF
      CHANCE: The rate of IUC removal was 8.8% (29/331) in the no additional screening
      group and 8.0% (27/341) in the additional laboratory screening group [IRR 1.1
      (95% CI 0.63-1.93)]. Unscheduled clinic attendances were similar in the two
      groups at 1 year of IUC insertion: 13.6% (45/331) in the no additional screening
      group and 12.3% (42/241) in the additional laboratory screening group. During the
      1-year follow-up, only five women, three from the no additional screening group
      and two from the additional laboratory screening group, developed pelvic
      inflammatory disease (PID), as defined by established diagnostic criteria.
      LIMITATIONS, REASONS FOR CAUTION: We were not able to carry out STI risk
      assessment directly from the men thus women with high-risk partners could have
      been included in the study and this may be responsible for the lack of a
      demonstrable effect of additional laboratory screening on incidence rates of IUC
      removals and unscheduled clinic attendance. The diagnosis of PID was based on
      clinical signs and symptoms; therefore, subclinical PID could have been missed.
      WIDER IMPLICATIONS OF THE FINDINGS: Among WLHA, the incidence rate of IUC removal
      is low and IUC continuation high. Syndromic screening for STIs could be
      sufficient in indentifying WLHA who are suitable for IUC use. However, our
      findings are only generalizable to women in HIV/AIDS care who have access to good
      follow-up. STUDY FUNDING/COMPETING INTERESTS: The study was supported by Medical
      Education for Equitable Services to all Ugandans, a Medical Education Partnership
      Initiative grant number 5R24TW008886 from the office of Global AIDS Coordinator
      and the US Department of Health and Human Services, Health Resources and Services
      Administration and National Institutes of Health. Additional funding was from the
      Swedish International Development Agency, Swedish Research Council (SIDA/VR). The
      authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: This
      trial was registered at Pan African Clinical Trial, Registry. PACTR
      201308000561212.

PMID- 25979375
TI  - The synthesis and biological activity of novel anthracenone-pyranones and
      anthracenone-furans.
AB  - An efficient and divergent methodology for the synthesis of new anthracenone
      pyranones and anthracenone-furans is described. Key reactions discussed in these
      syntheses include an aldehyde promoted annulation with a beta-keto-sulfoxide, a
      domino alkyne insertion/carbonylation/Nu-acylation and a DMEDA promoted Castro
      Stephens reaction. We also report the in vitro growth inhibition of these
      compounds in a range of human cancer cells. The natural product BE-26554A
      displayed good cell growth activity on BE2-C neuroblastoma and SMA glioblastoma
      cell lines at 0.17 and 0.16MUM (GI50), respectively. Of note, were a CF3
      functionalised anthracenone 4-pyranone (chromone) derivative 22, and an
      anthracenone-furan derivative 54 which displayed 0.20MUM and 0.38MUM growth
      inhibition, respectively, in the BE2-C neuroblastoma cell line.

PMID- 25979376
TI  - Development of fluorescent peptide substrates and assays for the key autophagy
      initiating cysteine protease enzyme, ATG4B.
AB  - An efficient assay for monitoring the activity of the key autophagy-initiating
      enzyme ATG4B based on a small peptide substrate has been developed. A number of
      putative small fluorogenic peptide substrates were prepared and evaluated and
      optimized compounds showed reasonable rates of cleavage but required high enzyme
      concentrations which limited their value. A modified peptide substrate
      incorporating a less sterically demanding self-immolative element was designed
      and synthesized and was shown to have enhanced properties useful for evaluating
      inhibitors of ATG4B. Substrate cleavage was readily monitored and was linear for
      up to 4h but enzyme concentrations of about ten-fold higher were required
      compared to assays using protein substrate LC3 or analogs thereof (such as FRET
      LC3). Several known inhibitors of ATG4B were evaluated using the small peptide
      substrate and gave IC50 values 3-7 fold higher than previously obtained values
      using the FRET-LC3 substrate.

PMID- 25979377
TI  - [Hysterical pseudo-coma: A case report].
AB  - Hysterical pseudo-coma corresponds to a state of clinical sleep with contrasting
      waking electroencephalogram. It can last several hours or even several days in
      the absence of an underlying organic disease. In psychiatry, this disorder is
      currently part of the "dissociative disorder not otherwise specified". Through
      this case report, we describe the evolution of a hysterical pseudo-coma that
      lasted four days in a 28-year-old man. The normality of biological, radiological
      and electroencephalographic assessments, and responsiveness of the patient during
      the implementation of a nasogastric tube, led us to suspect a mental origin. An
      adapted psychiatric care allowed the patient to recover his autonomy after three
      days of hospitalization. This had prevented the escalation of explorations and
      invasive treatments. However, the search for organic comorbidity and its
      management remains a priority. 

PMID- 25979378
TI  - [Court-ordered treatment: Analysing a complex practise through a literature
      review].
AB  - INTRODUCTION: In France, there are two main types of court-ordered treatment
      (COT) as far as mental health is concerned: obligations of treatment and
      injunctions of treatment. Obligations of treatment date back from 1958 whereas
      the law implementing injunctions of treatment is fairly recent as it was passed
      in 1998. Obligations and injunctions of treatment are two different types of COT
      that differ in terms of proceedings (obligations of treatment require no
      preliminary forensic psychiatric assessment; as for injunctions of treatment,
      they require the appointment of a coordinating medical doctor) and that are
      applied for different offences. However, both are psychiatric commitment
      procedures connecting the judicial, medical and social fields and their overall
      numbers have been on the rise. These common psychiatric practices have seldom
      been assessed and no review of the literature on the subject has ever been
      published. Better knowledge of such forensic practices is essential to their
      improvement and even to adjust the legal framework of these measures that are
      enjoying a boom. The purpose of this literature review is to define the
      prevalence of COT as well as the sociodemographic, criminal and psychiatric
      characteristics of those concerned by such measures. MATERIAL AND METHODS: A
      review of the French medical literature on COT was carried out using Science
      Direct up to December 2013. The results of seven studies were included and
      analysed. This was completed with a review of the articles listed in social
      sciences and law databases (Cairn and Dalloz). RESULTS: It has become
      increasingly frequent to rely on psychiatric teams to implement COT while at the
      same time public mental health services have to face a surge in activity with
      restricted financial means. Obligations of treatment are far more common (about
      20,000 court orders a year) than injunctions of treatment (about 4000 measures
      are currently being enforced). However the latter have showed an increase of 506%
      over the 2000 decade. Both measures mainly concern men (83-99%) who are rather
      low on the social scale. In about half of these men, no mental disorder was
      found, however the prevalence of personality disorders ranged from 22 to 65%
      while that of psychotic disorders was low. Injunctions of treatment concerned sex
      offenders (90% of cases) whereas obligations of treatment concern non-sexual
      abusers (40-70%) rather than sex offenders (20-30%). DISCUSSION: Psychiatric
      research on COT is still thin on the ground and its methodology does not allow
      rigorous evaluation though the use of such measures is growing. When confronted
      with people who have not sought any care or treatment, healthcare professionals
      are at a loss. In France, training in forensic psychiatry is inadequate and
      specialised healthcare (particularly for sex offenders) need improving to reach
      the level of those found in many other European countries. The purpose of
      psychiatric treatment differs from that of lawmakers whose aim is to prevent
      recidivism. However, better treatment consistency requires setting up
      partnerships between justice, health and social services. To improve connections,
      there are various avenues of work such as, for instance, the creation of
      coordinating medical doctors for injunctions of treatment in France or European
      experiments using a multidisciplinary approach to prevent recidivism in sex
      offenders. The framework of such a partnership remains to be created as it is
      part and parcel of COT but has not been provided for in the law. Healthcare
      jurisdictions as defined in the 2009 French National Health Law might provide an
      appropriate framework for mental health and law professionals to collaborate.

PMID- 25979379
TI  - Phosphodiesterase sequence variants may predispose to prostate cancer.
AB  - We hypothesized that mutations that inactivate phosphodiesterase (PDE) activity
      and lead to increased cAMP and cyclic guanosine monophosphate levels may be
      associated with prostate cancer (PCa). We sequenced the entire PDE coding
      sequences in the DNA of 16 biopsy samples from PCa patients. Novel mutations were
      confirmed in the somatic or germline state by Sanger sequencing. Data were then
      compared to the 1000 Genome Project. PDE, CREB and pCREB protein expression was
      also studied in all samples, in both normal and abnormal tissue, by
      immunofluorescence. We identified three previously described PDE sequence
      variants that were significantly more frequent in PCa. Four novel sequence
      variations, one each in the PDE4B,PDE6C, PDE7B and PDE10A genes, respectively,
      were also found in the PCa samples. Interestingly, PDE10A and PDE4B novel
      variants that were present in 19 and 6% of the patients were found in the tumor
      tissue only. In patients carrying PDE defects, there was pCREB accumulation
      (P<0.001), and an increase of the pCREB:CREB ratio (patients 0.97+/-0.03;
      controls 0.52+/-0.03; P-value <0.001) by immunohistochemical analysis. We
      conclude that PDE sequence variants may play a role in the predisposition and/or
      progression to PCa at the germline and/or somatic state respectively. 

PMID- 25979380
TI  - Notch1 pathway in adrenocortical carcinomas: correlations with clinical outcome.
AB  - Previous SNP array analyses have revealed genomic alterations of the Notch
      pathway as being the most frequent abnormality in adrenocortical tumors (ACTs).
      The aim of the present study was to evaluate the expression of components of
      Notch signaling in ACTs and to correlate them with clinical outcome. The mRNA
      expression of JAG1, NOTCH1, and selected target genes of NOTCH1 (HES1, HES5, and
      HEY2) was evaluated in 80 fresh frozen samples (28 normal adrenal glands (NAGs),
      24 adenomas (ACAs), and 28 carcinomas (ACCs)) by quantitative RT-PCR.
      Immunohistochemistry was performed in 221 tissues on paraffin slides (16 NAGs, 27
      ACAs, and 178 ACCs) for JAG1, activated NOTCH1 (aNOTCH1), and HEY2. An
      independent ACC validation cohort (n=77) was then also investigated. HEY2 mRNA
      expression was higher in ACCs than it was in ACAs (P<0.05). The protein
      expression of all of the factors was high (H-score 2-3) in a larger proportion of
      ACCs as compared to ACAs and NAGs (JAG1 in 27, 15, and 10%; aNOTCH1 in 13, 8, and
      0%; HEY2 in 66, 61, and 33% respectively, all P<0.001). High JAG1 expression was
      associated with earlier tumor stages and lower numbers of metastases in ACCs
      (both P=0.08) and favorably impacted overall and progression-free survival (PFS)
      (131 vs 30 months, hazard ratio (HR) 0.45, and 37 vs 9 months, HR 0.51, both
      P<0.005). This impact on overall survival (OS) was confirmed in the validation
      cohort. No such association was observed for aNOTCH1 or HEY2. In conclusion,
      different components of the Notch1 signaling pathway are overexpressed in ACCs,
      which suggests a role for the pathway in malignant transformation. However, JAG1
      is overexpressed in a subgroup of ACCs with a better clinical outcome. 

PMID- 25979381
TI  - Subjective valuation of cushioning in a human drop landing task as quantified by
      trade-offs in mechanical work.
AB  - Humans can perform motor tasks in a variety of ways, yet often favor a particular
      strategy. Some factors governing the preferred strategy may be objective and
      quantifiable, (e.g. metabolic energy or mechanical work) while others may be more
      subjective and less measurable, (e.g. discomfort, pain, or mental effort).
      Subjectivity can make it challenging to explain or predict preferred movement
      strategies. We propose that subjective factors might nevertheless be
      characterized indirectly by their trade-offs against more objective measures such
      as work. Here we investigated whether subjective costs that influence human
      movement during drop landings could be indirectly assessed by quantifying
      mechanical work performed. When landing on rigid ground, humans typically absorb
      much of the collision actively by bending their knees, perhaps to avoid the
      discomfort of stiff-legged landings. We measured how work performed by healthy
      adults (N=8) changed as a function of surface cushioning for drop landings (fixed
      at about 0.4m) onto varying amounts of foam. Landing on more foam dissipated more
      energy passively in the surface, thus reducing the net dissipation required of
      subjects, due to relatively fixed landing energy. However, subjects actually
      performed even less work in the dissipative collision, as well as in the
      subsequent active, positive work to return to upright stance (approximately
      linear decrease of about 1.52 J per 1 cm of foam thickness). As foam thickness
      increased, there was also a corresponding reduction in center-of-mass vertical
      displacement after initial impact by up to 43%. Humans appear to subjectively
      value cushioning, revealed by the extra work they perform landing without it.
      Cushioning is thus worth more than the energy it dissipates, in an amount that
      indicates the subjective discomfort of stiff landings.

PMID- 25979382
TI  - Patient-specific numerical simulation of stent-graft deployment: Validation on
      three clinical cases.
AB  - Endovascular repair of abdominal aortic aneurysms faces some adverse outcomes,
      such as kinks or endoleaks related to incomplete stent apposition, which are
      difficult to predict and which restrain its use although it is less invasive than
      open surgery. Finite element simulations could help to predict and anticipate
      possible complications biomechanically induced, thus enhancing practitioners'
      stent-graft sizing and surgery planning, and giving indications on patient
      eligibility to endovascular repair. The purpose of this work is therefore to
      develop a new numerical methodology to predict stent-graft final deployed shapes
      after surgery. The simulation process was applied on three clinical cases, using
      preoperative scans to generate patient-specific vessel models. The marketed
      devices deployed during the surgery, consisting of a main body and one or more
      iliac limbs or extensions, were modeled and their deployment inside the
      corresponding patient aneurysm was simulated. The numerical results were compared
      to the actual deployed geometry of the stent-grafts after surgery that was
      extracted from postoperative scans. We observed relevant matching between
      simulated and actual deployed stent-graft geometries, especially for proximal and
      distal stents outside the aneurysm sac which are particularly important for
      practitioners. Stent locations along the vessel centerlines in the three
      simulations were always within a few millimeters to actual stents locations. This
      good agreement between numerical results and clinical cases makes finite element
      simulation very promising for preoperative planning of endovascular repair. 

PMID- 25979384
TI  - Patient specific stress and rupture analysis of ascending thoracic aneurysms.
AB  - An ascending thoracic aortic aneurysm (ATAA) is a serious medical condition
      which, more often than not, requires surgery. Aneurysm diameter is the primary
      clinical criterion for determining when surgical intervention is necessary but,
      biomechanical studies have suggested that the diameter criterion is insufficient.
      This manuscript presents a method for obtaining the patient specific wall stress
      distribution of the ATAA and the retrospective rupture risk for each patient.
      Five human ATAAs and the preoperative dynamic CT scans were obtained during
      elective surgeries to replace each patient's aneurysm with a synthetic graft. The
      material properties and rupture stress for each tissue sample were identified
      using bulge inflation tests. The dynamic CT scans were used to generate patient
      specific geometries for a finite element (FE) model of each patient's aneurysm.
      The material properties from the bulge inflation tests were implemented in the FE
      model and the wall stress distribution at four different pressures was estimated.
      Three different rupture risk assessments were compared: the maximum diameter, the
      rupture risk index, and the overpressure index. The peak wall stress values for
      the patients ranged from 28% to 94% of the ATAA's failure stress. The rupture
      risk and overpressure indices were both only weakly correlated with diameter
      (rho=-0.29, both cases). In the future, we plan to conduct a large experimental
      and computational study that includes asymptomatic patients under surveillance,
      patients undergoing elective surgery, and patients who have experienced rupture
      or dissection to determine if the rupture risk index or maximum diameter can
      meaningfully differentiate between the groups. 

PMID- 25979383
TI  - Sensitivity of predicted muscle forces during gait to anatomical variability in
      musculotendon geometry.
AB  - Scaled generic musculoskeletal models are commonly used to drive dynamic
      simulations of motions. It is however, acknowledged that not accounting for
      variability in musculoskeletal geometry and musculotendon parameters may confound
      the simulation results, even when analysing control subjects. This study
      documents the three-dimensional anatomical variability of musculotendon origins
      and insertions of 33 lower limb muscles determined based on magnetic resonance
      imaging in six subjects. This anatomical variability was compared to the
      musculotendon point location in a generic musculoskeletal model. Furthermore, the
      sensitivity of muscle forces during gait, calculated using static optimization,
      to perturbations of the musculotendon point location was analyzed with a generic
      model. More specific, a probabilistic approach was used: for each analyzed
      musculotendon point, the three-dimensional location was re-sampled with a uniform
      Latin hypercube method within the anatomical variability and the static
      optimization problem was then re-solved for all perturbations. We found that
      musculotendon point locations in the generic model showed only variable
      correspondences with the anatomical variability. The anatomical variability of
      musculotendon point location did affect the calculated muscle forces: muscles
      most sensitive to perturbations within the anatomical variability are iliacus and
      psoas. Perturbation of the gluteus medius anterior, iliacus and psoas induces the
      largest concomitant changes in muscle forces of the unperturbed muscles.
      Therefore, when creating subject-specific musculoskeletal models, these
      attachment points should be defined accurately. In addition, the size of the
      anatomical variability of the musculotendon point location was not related to the
      sensitivity of the calculated muscle forces. 

PMID- 25979385
TI  - [Are anti-TNF-alpha agents really useful in systemic vasculitis? Experience in
      polyarteritis nodosa].

PMID- 25979387
TI  - [Ultrasound-guided cannulation of the brachiocephalic vein in neonates and
      infants].
AB  - INTRODUCTION: Central venous catheter (CVC) insertion in neonates and small
      infants is a challenging and high risk procedure. Ultrasound (US) guided
      cannulation increases the success rate and reduces procedural-related
      complications. The internal jugular vein is the most frequent site for US-guided
      CVC insertion. However this approach is technically demanding in neonates and
      small infants. US-guided supraclavicular cannulation of the brachiocephalic vein
      (BCV) is a new approach that may be advantageous in case of difficult central
      venous catheterization. We present our preliminary experience with this technique
      in a case series of neonates and small infants. METHODS: Case series of neonates
      and small infants weighing less than 5kg, in whom US-guided supraclavicular
      cannulation of the BCV was attempted. A longitudinal "in plane" supraclavicular
      approach to the BCV was performed using a 12Hz linear or a 8Hz microconvex
      transducer. All cannulations were performed by the same operator, a pediatrician
      with previous experience in US-guided central venous catheterization. RESULTS:
      The study included 6 patients with a median (range) weight of 2.1 (0.94-4.1) kg
      and age of 1.9 (0.6-4) months. Two cases required 2 punctures, while cannulation
      was achieved at the first attempt in the remaining 4 cases. There were no
      procedural or catheter-related complications. CVCs were withdrawn after 9 (6-15)
      days. CONCLUSIONS: The US-guided supraclavicular approach to the BCV is a
      feasible and safe alternative in neonates and very small infants. More studies
      are needed to define the role of this new venous access before its routine
      application in daily practice.

PMID- 25979386
TI  - [Sedation and analgesia practices among Spanish neonatal intensive care units].
AB  - INTRODUCTION: Pain management and sedation is a priority in neonatal intensive
      care units. A study was designed with the aim of determining current clinical
      practice as regards sedation and analgesia in neonatal intensive care units in
      Spain, as well as to identify factors associated with the use of sedative and
      analgesic drugs. METHOD: A multicenter, observational, longitudinal and
      prospective study. RESULTS: Thirty neonatal units participated and included 468
      neonates. Of these, 198 (42,3%) received sedatives or analgesics. A total of 19
      different drugs were used during the study period, and the most used was
      fentanyl. Only fentanyl, midazolam, morphine and paracetamol were used in at
      least 20% of the neonates who received sedatives and/or analgesics. In infusions,
      14 different drug prescriptions were used, with the most frequent being fentanyl
      and the combination of fentanyl and midazolam. The variables associated with
      receiving sedation and/or analgesia were, to have required invasive ventilation
      (P<.001; OR=23.79), a CRIB score >3 (P=.023; OR=2.26), the existence of pain
      evaluation guides in the unit (P<.001; OR=3.82), and a pain leader (P=.034;
      OR=2.35). CONCLUSIONS: Almost half of the neonates admitted to intensive care
      units receive sedatives or analgesics. There is significant variation between
      Spanish neonatal units as regards sedation and analgesia prescribing. Our results
      provide evidence on the "state of the art", and could serve as the basis of
      preparing clinical practice guidelines at a national level.

PMID- 25979388
TI  - [Focal nodular hyperplasia: A diagnosis to consider in a hepatic mass].

PMID- 25979389
TI  - Epidemiology of head and neck cancer.
AB  - This article discusses risk factors, incidence trends, and prognostic
      considerations for head and neck cancer (HNC). The primary causes of HNC are
      tobacco and alcohol use, and human papillomavirus (HPV). Tobacco-related HNC
      incidence rates are decreasing in countries where tobacco use has declined. HPV
      HNC, which occurs primarily in the oropharynx and is associated with sexual
      behaviors, has been increasing over the past several decades, among white men in
      particular. The prognosis for HNC overall has improved slightly since the 1990s,
      and is influenced by site, stage, and HPV status. Prognosis for HPV-HNC is
      significantly better than for HPV-negative disease. 

PMID- 25979391
TI  - Examination of the patient with head and neck cancer.
AB  - Head and neck cancer typically refers to epithelial malignancies of the upper
      aerodigestive tract and may include neoplasms of the thyroid, salivary glands,
      and soft tissue, bone sarcomas, and skin cancers. Two-thirds of patients present
      with advanced disease involving regional lymph nodes at the time of diagnosis. A
      thorough history and detailed examination are integral to oncologic staging and
      treatment planning. This article begins with an overview of the head and neck
      examination (with special attention to detailed findings with clinical
      implications), followed by a discussion of the major head and neck subsites, and
      clinical pearls surrounding the examination. 

PMID- 25979390
TI  - Molecular biology and immunology of head and neck cancer.
AB  - In recent years, our knowledge and understanding of head and neck squamous cell
      carcinoma (HNSCC) has expanded dramatically. New high-throughput sequencing
      technologies have accelerated these discoveries since the first reports of whole
      exome sequencing of HNSCC tumors in 2011. In addition, the discovery of human
      papillomavirus in relationship with oropharyngeal squamous cell carcinoma has
      shifted our molecular understanding of the disease. New investigation into the
      role of immune evasion in HNSCC has also led to potential novel therapies based
      on immune-specific systemic therapies. 

PMID- 25979392
TI  - Radiation treatment of head and neck cancer.
AB  - Radiation therapy plays a central and continuously evolving role in the treatment
      of head and neck cancer. In this review, some basic principles of radiation
      oncology are explained and common clinical scenarios are addressed in which
      radiation therapy forms part of the treatment course, with a focus on issues most
      pertinent to the interaction of radiation oncology with surgical treatment. These
      issues include refinement of the indications guiding the choice of adjuvant
      radiation therapy or chemoradiotherapy, sequencing and timing of therapies before
      or after definitive surgical management, and scientific and technical advances
      with the potential to reduce radiation-related toxicity. 

PMID- 25979393
TI  - Systemic therapy for squamous cell carcinoma of the head and neck.
AB  - The use of systemic therapy as part of curative treatment and palliation is an
      evolving paradigm for squamous cell cancer of the head and neck (SCCHN), which
      historically has been treated with local modalities. At present, the treatment
      armamentarium includes traditional cytotoxic therapy, targeted biological agents,
      and emerging immunotherapeutics. This article discusses the use of all of these
      systemic approaches for the curative and palliative treatment of SCCHN. 

PMID- 25979394
TI  - Imaging for head and neck cancer.
AB  - Imaging is an essential tool in the management of head and neck cancer. Oral,
      oropharyngeal, laryngeal, and hypopharyngeal lesions are initially imaged with
      computed tomography (CT) because it allows rapid image acquisition and reduces
      artifacts related to respiration and swallowing, which can degrade image quality
      and limit evaluation. Sinonasal, nasopharyngeal, and salivary gland tumors are
      better approached with MRI because it allows for better delineation of tumor
      extent. PET/CT is usually reserved for advanced disease to evaluate for distant
      metastatic disease and posttreatment residual and recurrent disease. Imaging is
      best used in combination with expert clinical and physical examination. 

PMID- 25979395
TI  - Principles and practice of reconstructive surgery for head and neck cancer.
AB  - Reconstruction after surgical treatment of head and neck cancers can be
      challenging. Goals for reconstruction include restoration of appearance as well
      as function when appropriate. Commonly encountered sites requiring reconstruction
      include the soft tissues of the face (including the critical areas of the eyes,
      ears, nose, and lips), scalp, tongue and oral cavity, maxilla, mandible, and
      pharynx. Advanced reconstructive techniques using microsurgery may be preferable
      to simpler techniques to obtain optimal outcomes. In this article, techniques for
      reconstruction in these areas as well as anticipated outcomes are discussed. 

PMID- 25979397
TI  - Cancer of the oropharynx.
AB  - The oropharynx has a crucial role in swallowing because of the surrounding
      constrictor musculature, need for mobility and pliability, and proximity of the
      base of tongue to the larynx. Human papilloma virus (HPV) infection as a cause of
      oropharyngeal squamous cell carcinoma has increased dramatically in proportion
      and overall numbers of oropharyngeal squamous cell carcinoma cases. Better
      clinical response to therapy and younger age of the HPV+ oropharyngeal squamous
      cell carcinoma patients have caused functional and quality-of-life considerations
      to become more important endpoints in evaluating efficacy of therapeutic options;
      "deintensification" to ameliorate toxicity is under investigation for this
      population. 

PMID- 25979396
TI  - Cancer of the oral cavity.
AB  - Cancer of the oral cavity is one of the most common malignancies worldwide.
      Although early diagnosis is relatively easy, presentation with advanced disease
      is not uncommon. The standard of care is primary surgical resection with or
      without postoperative adjuvant therapy. Improvements in surgical techniques
      combined with the routine use of postoperative radiation or chemoradiation
      therapy have resulted in improved survival. Successful treatment is predicated on
      multidisciplinary treatment strategies to maximize oncologic control and minimize
      impact of therapy on form and function. Prevention of oral cancer requires better
      education about lifestyle-related risk factors, and improved awareness and tools
      for early diagnosis. 

PMID- 25979398
TI  - Treatment/Comparative therapeutics: cancer of the larynx and hypopharynx.
AB  - This article reviews the management of laryngeal and hypopharyngeal squamous cell
      carcinoma. Available therapies for early and late stage cancers are discussed,
      and the literature is reviewed. The indications and outcomes of surgical and
      nonsurgical modalities are discussed and compared. 

PMID- 25979399
TI  - Nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma is uncommon in the United States, with only 0.2 to 0.5
      cases per 100,00 people; this is in contrast to southern China and Hong Kong,
      where the incidence is 25 to 50 per 100,000 people. There is a potential link
      between Epstein-Barr virus and the development of nasopharyngeal carcinoma.
      Radiotherapy alone as a single modality leads to similar 10-year survival rates
      in United States, Denmark, and Hong Kong (34%, 37%, and 43%, respectively).
      Multiple studies have shown an advantage to concurrent chemoradiation in the
      treatment of advanced disease. Radiation therapy remains the mainstay of salvage
      therapy, and modern techniques have allowed clinicians to achieve adequate local
      control without excessive toxicity. 

PMID- 25979401
TI  - Evaluation and management of head and neck squamous cell carcinoma of unknown
      primary.
AB  - The diagnostic evaluation and therapeutic management of a patient with squamous
      cell carcinoma of an unknown primary (SCCUP) has considerably evolved over recent
      decades and will likely continue to change as a result of the improving ability
      to identify small primary tumors and better tailor the implementation of
      multimodality therapy. By application of the general principles of head and neck
      oncology, physicians and surgeons are often able to achieve satisfactory control
      of the disease in patients with SCCUP. 

PMID- 25979400
TI  - Cancers of the nose, sinus, and skull base.
AB  - Malignancies of the nose, sinus, and skull base are rare. The most common
      histologies are squamous cell carcinoma and adenocarcinoma. The most common
      primary sites are the nasal cavity and maxillary sinus. Management of these
      tumors is technically challenging because they often present in advanced stages
      with extensive disease invading important structures such as the orbit and the
      skull base. In the last few decades advances in surgical resection techniques, as
      well as improved strategies to deliver adjuvant radiation, have substantially
      improved the outcomes in patients with malignancies of the sinonasal tract and
      skull base. 

PMID- 25979402
TI  - Cutaneous malignancy of the head and neck.
AB  - Most skin cancers of the head and neck are nonmelanoma skin cancers (NMSCs).
      Basal cell carcinoma and squamous cell carcinoma are the most frequent types of
      NMSCs. Treatment options including wide local excision, Mohs surgery, sentinel
      lymph node biopsy, and cervical lymphadenectomy and adjuvant radiation when
      warranted offer a high cure rate, while balancing excellent functional and
      cosmetic outcomes. Evaluation by a multidisciplinary team is highly recommended
      with advanced and aggressive lesions. Avoidance of sunburns and acute sun damage,
      sunscreen protection, and early identification and evaluation of suspicious
      lesions remain the first line of defense against skin cancers. 

PMID- 25979403
TI  - Cancers of major salivary glands.
AB  - Major salivary gland malignancies are a rare but histologically diverse group of
      entities. Establishing the diagnosis of a malignant salivary neoplasm may be
      challenging because of the often minimally symptomatic nature of the disease, and
      limitations of imaging modalities and cytology. Treatment is centered on surgical
      therapy and adjuvant radiation in selected scenarios. Systemic therapy with
      chemotherapeutic agents and monoclonal antibodies lacks evidence in support of
      its routine use. 

PMID- 25979404
TI  - A long overdue discussion of head and neck cancer.

PMID- 25979405
TI  - Why "head and neck cancer"?

PMID- 25979406
TI  - Ultrasonography for Screening and Follow-Up of Diaphragmatic Dysfunction in the
      ICU: A Pilot Study.
AB  - PURPOSE: Reversibility and impact of diaphragmatic dysfunction (DD) are unknown.
      The principal aim was to describe diaphragmatic function as assessed by
      ultrasonography during weaning trials. MATERIALS AND METHODS: The present study
      is a 6-month single-center prospective study. All patients under mechanical
      ventilation for more than 7 days and eligible for a spontaneous breathing trial
      (SBT) were enrolled prospectively. INTERVENTION: Two blinded ultrasonographers
      evaluated each hemidiaphragm during SBT. Prevalence of DD among weaning failure
      and death and interobserver reproducibility have been evaluated. RESULTS: The 34
      included patients had a mean Simplified Acute Physiology Score version II of 55.7
      +/- 14 and a median intensive care unit (ICU) stay length of 17 days (13-30).
      Diaphragmatic dysfunction was found in 13 (38%) patients, on both sides in 8.
      Bilateral DD resolved before ICU discharge in 5 of the 7 reevaluated patients. No
      weaning failures were recorded. The ICU mortality was higher in patients with DD
      (37% vs 5%, P = .048). Mean interobserver agreement rate was 91%. Reproducibility
      was better with M-mode. CONCLUSION: The ICU-acquired DD usually improves before
      ICU discharge but might constitute a marker for greater disease severity. The
      present preliminary results require confirmation in a larger prospective
      multicenter study.

PMID- 25979407
TI  - From the editor.

PMID- 25979408
TI  - Should blood pressure be lowered in acute ischemic stroke? The CATIS trial.

PMID- 25979409
TI  - Blood pressure targets in patients with diabetes--a new perspective.

PMID- 25979410
TI  - Renal denervation therapy for hypertension: pathways for moving development
      forward.
AB  - This scientific statement provides a summary of presentations and discussions at
      a cardiovascular Think Tank co-sponsored by the American Society of Hypertension
      (ASH), the United States Food and Drug Administration (FDA), and the National
      Heart, Lung, and Blood Institute (NHLBI) held in North Bethesda, Maryland, on
      June 26, 2014. Studies of device therapies for the treatment of hypertension are
      requested by regulators to evaluate their safety and efficacy during their
      development programs. Think Tank participants thought that important
      considerations in undertaking such studies were: (1) Preclinical assessment: how
      likely it is that both efficacy and safety data indicating benefit in humans will
      be obtained, and/or whether a plausible mechanism of action for efficacy can be
      identified; (2) Early human trial(s): the ability to determine that the device
      has an acceptable benefit-to-risk balance for its use in the intended patient
      population and without the influence of drug therapy during a short-term follow
      up period; and (3) Pivotal Phase III trial(s): the ability to prove the
      effectiveness of the device in a broad population in which the trial can be made
      as non-confounded as possible while still allowing for the determination for
      benefits when added to antihypertensive therapies.

PMID- 25979411
TI  - Lack of blood pressure difference by race in professional American football
      players.
AB  - Previous findings suggest that professional American football players have higher
      blood pressures (BP) and a higher prevalence of pre-hypertension and hypertension
      than the general population. We sought to determine whether race is associated
      with differences in BP and prevalence of pre-hypertension and hypertension among
      a large sample of professional football players. BP was measured at 2009 team
      mini-camps for 1484 black (n = 1007) and white (n = 477) players from 27 National
      Football League (NFL) teams. Players were categorized into three position groups
      based on body mass index (BMI). There was no racial difference in mean systolic
      or diastolic BP in any of the three position groups. There were no racial
      differences in prevalence of hypertension (99 [9.8%] black players vs. 39 [8.2%]
      white players; P = .353) or pre-hypertension (557 [55.3%] black players vs. 264
      [55.3%] white players; P = 1.0). Contrary to findings in the general population,
      BP and prevalence of pre-hypertension/hypertension did not vary with race in a
      large population of active NFL players.

PMID- 25979412
TI  - Refractory and resistant hypertension: characteristics and differences observed
      in a specialized clinic.
AB  - Resistant hypertension (RH) is defined as uncontrolled blood pressure (BP)
      despite the use of >=3 anti-hypertensive drugs, or controlled requiring use of
      >=4 drugs. Recently, a new definition for an extreme phenotype of RH
      (uncontrolled BP using at least five drugs) has emerged-the refractory
      hypertension (RfH). Although characteristics of RH are well established, little
      is known about this newly described subgroup. For this work, 116 subjects with RH
      were enrolled from a specialized clinic and divided into RH (n = 80) and RfH (n =
      36). Subjects were submitted to echocardiography, 24-hour ambulatory BP
      measurement and biochemical analyses. Logistic regression analysis demonstrated
      that: (1) white-coat effect (odds ratio [OR], 3.23; 95% confidence interval [CI],
      1.12-9.27; P = .03), (2) black race (OR, 6.67; 95% CI, 1.99-16.16; P < .001), and
      (3) left ventricular mass index (OR, 1.02; 95% CI, 1.01-1.03; P = .04) were
      independent predictors of refractoriness. In conclusion, RfH and RH present
      different patient characteristics, and these phenotypic aspects can be useful for
      better understanding this harder-to-treat subgroup.

PMID- 25979413
TI  - Hypertension--an emerging cardiovascular risk factor in HIV infection.
AB  - Patients with HIV may have an increased risk of hypertension and cardiovascular
      disease (CVD). The objective of this study was to determine the prevalence and
      risk factors for hypertension in a population of HIV-infected patients at an
      HIV/AIDS clinic in southern Brazil. We reviewed medical records of 1009 HIV
      infected patients aged 18 years or more in an urban HIV/AIDS clinic based in
      Porto Alegre, southern Brazil. Hypertension was defined according to the Eighth
      Joint National Committee criteria. The prevalence of hypertension in this study
      cohort was 22.5% (95% confidence interval, 20%-25.2%). Individuals were
      significantly older in the hypertensive group (P < .001). After adjustment using
      a Poisson regression model of all variables that presented P < .2 in the
      univariate analysis, the variables that were significantly associated with
      hypertension were only age >=40 years and obesity. Also in this setting,
      dyslipidemia (P = .068) showed a tendency of association with hypertension.
      Compared with HIV-infected persons aged 18-39 years, those aged 40-59 years
      presented a 2-fold higher prevalence of hypertension (95% confidence interval,
      1.2-3.3).The present study showed a high prevalence of hypertension among HIV
      infected persons, similar to other studies, ranging from 13% to 45%, and also
      similar to the HIV-negative general population. Age and obesity were the factors
      associated with hypertension. Finally, the present study indicates a similar
      pattern of behavior and comorbidities for HIV-positive and -negative patients in
      relation to hypertension.

PMID- 25979414
TI  - Regarding "Subclinical carotid artery disease and plasma homocysteine levels in
      patients with hypertension".

PMID- 25979415
TI  - Measuring health system performance: A new approach to accountability and quality
      improvement in New Zealand.
AB  - In February 2014, the New Zealand Ministry of Health released a new framework for
      measuring the performance of the New Zealand health system. The two key aims are
      to strengthen accountability to taxpayers and to lift the performance of the
      system's component parts using a 'whole-of-system' approach to performance
      measurement. Development of this new framework--called the Integrated Performance
      and Incentive Framework (IPIF)--was stimulated by a need for a performance
      management framework which reflects the health system as a whole, which
      encourages primary and secondary providers to work towards the same end, and
      which incorporates the needs and priorities of local communities. Measures within
      the IPIF will be set at two levels: the system level, where measures are set
      nationally, and the local district level, where measures which contribute towards
      the system level indicators will be selected by local health alliances. In the
      first year, the framework applies only at the system level and only to primary
      health care services. It will continue to be developed over time and will
      gradually be extended to cover a wide range of health and disability services.
      The success of the IPIF in improving health sector performance depends crucially
      on the willingness of health sector personnel to engage closely with the
      measurement process.

PMID- 25979416
TI  - Health, economic crisis, and austerity: A comparison of Greece, Finland and
      Iceland.
AB  - Reports have attributed a public health tragedy in Greece to the Great Recession
      and the subsequent application of austerity programs. It is also claimed that the
      comparison of Greece with Iceland and Finland-where austerity policies were not
      applied-reveals the harmful effect of austerity on health and that by protecting
      spending in health and social budgets, governments can offset the harmful effects
      of economic crises on health. We use data on life expectancy, mortality rates,
      incidence of infectious diseases, rates of vaccination, self-reported health and
      other measures to examine the evolution of population health and health services
      performance in Greece, Finland and Iceland since 1990-2011 or 2012-the most
      recent years for which data are available. We find that in the three countries
      most indicators of population health continued improving after the Great
      Recession started. In terms of population health and performance of the health
      care system, in the period after 2007 for which data are available, Greece did as
      good as Iceland and Finland. The evidence does not support the claim that there
      is a health crisis in Greece. On the basis of the extant evidence, claims of a
      public health tragedy in Greece seem overly exaggerated. 

PMID- 25979417
TI  - Acoustic Cavitation-Mediated Delivery of Small Interfering Ribonucleic Acids with
      Phase-Shift Nano-Emulsions.
AB  - Localized, targeted delivery of small interfering ribonucleic acid (siRNA) has
      been the foremost hurdle in the use of siRNA for the treatment of various
      diseases. Major advances have been achieved in the synthesis of siRNA, which have
      led to greater target messenger RNA (mRNA) silencing and stability under
      physiologic conditions. Although numerous delivery strategies have shown promise,
      there are still limited options for targeted delivery and release of siRNA
      administered systemically. In this in vitro study, phase-shift nano-emulsions
      (PSNE) were explored as cavitation nuclei to facilitate free siRNA delivery to
      cancer cells via sonoporation. A cell suspension containing varying amounts of
      PSNE and siRNA was exposed to 5-MHz pulsed ultrasound at fixed settings (6.2-MPa
      peak negative pressure, 5-cycle pulses, 250-Hz pulse repetition frequency (PRF)
      and total exposure duration of 100 s). Inertial cavitation emissions were
      detected throughout the exposure using a passive cavitation detector. Successful
      siRNA delivery was achieved (i.e., >50% cell uptake) with high (>80%) viability.
      The percentage of cells with siRNA uptake was correlated with the amount of
      inertial cavitation activity generated from vaporized PSNE. The siRNA remained
      functional after delivery, significantly reducing expression of green fluorescent
      protein in a stably transfected cell line. These results indicate that vaporized
      PSNE can facilitate siRNA entry into the cytosol of a majority of sonicated cells
      and may provide a non-endosomal route for siRNA delivery. 

PMID- 25979419
TI  - The translocon protein Sec61 mediates antigen transport from endosomes in the
      cytosol for cross-presentation to CD8(+) T cells.
AB  - The molecular mechanisms regulating antigen translocation into the cytosol for
      cross-presentation are under controversial debate, mainly because direct data is
      lacking. Here, we have provided direct evidence that the activity of the
      endoplasmic reticulum (ER) translocon protein Sec61 is essential for endosome-to
      cytosol translocation. We generated a Sec61-specific intrabody, a crucial tool
      that trapped Sec61 in the ER and prevented its recruitment into endosomes without
      influencing Sec61 activity and antigen presentation in the ER. Expression of this
      ER intrabody inhibited antigen translocation and cross-presentation,
      demonstrating that endosomal Sec61 indeed mediates antigen transport across
      endosomal membranes. Moreover, we showed that the recruitment of Sec61 toward
      endosomes, and hence antigen translocation and cross-presentation, is dependent
      on dendritic cell activation by Toll-like receptor (TLR) ligands. These data shed
      light on a long-lasting question regarding antigen cross-presentation and point
      out a role of the ER-associated degradation machinery in compartments distinct
      from the ER. 

PMID- 25979418
TI  - Structure of the Complex of F-Actin and DNGR-1, a C-Type Lectin Receptor Involved
      in Dendritic Cell Cross-Presentation of Dead Cell-Associated Antigens.
AB  - DNGR-1 is a C-type lectin receptor that binds F-actin exposed by dying cells and
      facilitates cross-presentation of dead cell-associated antigens by dendritic
      cells. Here we present the structure of DNGR-1 bound to F-actin at 7.7 A
      resolution. Unusually for F-actin binding proteins, the DNGR-1 ligand binding
      domain contacts three actin subunits helically arranged in the actin filament,
      bridging over two protofilaments, as well as two neighboring actin subunits along
      one protofilament. Mutation of residues predicted to mediate ligand binding led
      to loss of DNGR-1-dependent cross-presentation of dead cell-associated antigens,
      formally demonstrating that the latter depends on F-actin recognition. Notably,
      DNGR-1 has relatively modest affinity for F-actin but multivalent interactions
      allow a marked increase in binding strength. Our findings shed light on modes of
      actin binding by cellular proteins and reveal how extracellular detection of
      cytoskeletal components by dedicated receptors allows immune monitoring of loss
      of cellular integrity.

PMID- 25979420
TI  - FAS Inactivation Releases Unconventional Germinal Center B Cells that Escape
      Antigen Control and Drive IgE and Autoantibody Production.
AB  - The mechanistic links between genetic variation and autoantibody production in
      autoimmune disease remain obscure. Autoimmune lymphoproliferative syndrome (ALPS)
      is caused by inactivating mutations in FAS or FASL, with autoantibodies thought
      to arise through failure of FAS-mediated removal of self-reactive germinal center
      (GC) B cells. Here we show that FAS is in fact not required for this process.
      Instead, FAS inactivation led to accumulation of a population of unconventional
      GC B cells that underwent somatic hypermutation, survived despite losing antigen
      reactivity, and differentiated into a large population of plasma cells that
      included autoantibody-secreting clones. IgE(+) plasma cell numbers, in
      particular, increased after FAS inactivation and a major cohort of ALPS-affected
      patients were found to have hyper-IgE. We propose that these previously
      unidentified cells, designated "rogue GC B cells," are a major driver of
      autoantibody production and provide a mechanistic explanation for the linked
      production of IgE and autoantibodies in autoimmune disease.

PMID- 25979421
TI  - Integrin alphavbeta8-Mediated TGF-beta Activation by Effector Regulatory T Cells
      Is Essential for Suppression of T-Cell-Mediated Inflammation.
AB  - Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell
      responses, but how Treg cells mediate suppression to maintain immune homeostasis
      and limit responses during inflammation is unclear. Here we show that effector
      Treg cells express high amounts of the integrin alphavbeta8, which enables them
      to activate latent transforming growth factor-beta (TGF-beta). Treg-cell-specific
      deletion of integrin alphavbeta8 did not result in a spontaneous inflammatory
      phenotype, suggesting that this pathway is not important in Treg-cell-mediated
      maintenance of immune homeostasis. However, Treg cells lacking expression of
      integrin alphavbeta8 were unable to suppress pathogenic T cell responses during
      active inflammation. Thus, our results identify a mechanism by which Treg cells
      suppress exuberant immune responses, highlighting a key role for effector Treg
      cell-mediated activation of latent TGF-beta in suppression of self-harmful T cell
      responses during active inflammation.

PMID- 25979422
TI  - The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell
      Autophagy and Alters T Cell Selection.
AB  - CLEC16A variation has been associated with multiple immune-mediated diseases,
      including type 1 diabetes, multiple sclerosis, systemic lupus erythematosus,
      celiac disease, Crohn's disease, Addison's disease, primary biliary cirrhosis,
      rheumatoid arthritis, juvenile idiopathic arthritis, and alopecia areata. Despite
      strong genetic evidence implicating CLEC16A in autoimmunity, this gene's broad
      association with disease remains unexplained. We generated Clec16a knock-down
      (KD) mice in the nonobese diabetic (NOD) model for type 1 diabetes and found that
      Clec16a silencing protected against autoimmunity. Disease protection was
      attributable to T cell hyporeactivity, which was secondary to changes in thymic
      epithelial cell (TEC) stimuli that drive thymocyte selection. Our data indicate
      that T cell selection and reactivity were impacted by Clec16a variation in thymic
      epithelium owing to Clec16a's role in TEC autophagy. These findings provide a
      functional link between human CLEC16A variation and the immune dysregulation that
      underlies the risk of autoimmunity.

PMID- 25979423
TI  - What matters to patients with heart failure? The influence of non-health-related
      goals on patient adherence to self-care management.
AB  - OBJECTIVE: To describe the life goals of heart failure (HF) patients and to
      determine whether adherence is influenced by the extent to which these priorities
      are perceived as compatible with HF self-care regimens. METHOD: Forty HF
      outpatients identified their top-five life goals and indicated the compatibility
      of HF self-care regimens (diet, exercise, weighing) with these priorities. HF
      knowledge, self-efficacy and reported adherence were also assessed. RESULTS:
      Patients valued autonomy and social relationships as much as physical health.
      However, the rated importance of these domains did not predict adherence.
      Adherence positively correlated with the extent to which the regimen,
      specifically exercise, was considered compatible with life goals (r=.34, p<.05).
      Exercise adherence also correlated with illness severity and self-efficacy (rs=
      .42 and .36, p<.05, respectively). The perceived compatibility of physical
      activity with personal goals predicted 11% of the variance in exercise adherence
      above and beyond that accounted for by illness severity and self-efficacy (FDelta
      (1, 36)=7.11, p<.05). CONCLUSIONS: Patients' goals outside of the illness
      management context influence self-care practices. PRACTICE IMPLICATIONS:
      Exploring patients' broad life goals may increase opportunities to resolve
      ambivalence and enhance motivation for self-care adherence.

PMID- 25979424
TI  - Outflow Occlusion with Occipital Artery-Posterior Inferior Cerebellar Artery
      Bypass for Growing Vertebral Artery Fusiform Aneurysm with Ischemic Onset: A Case
      Report.
AB  - Surgical treatments should be considered for vertebral artery fusiform aneurysms,
      which become symptomatic due to cerebral ischemia or mass effect. Ischemic
      complication is one of the major problems after surgical or endovascular
      trapping, which is associated with unfavorable outcomes. The authors present a
      case with growing vertebral artery (VA) fusiform aneurysm with ischemic onset
      successfully treated with outflow occlusion with occipital artery-posterior
      inferior cerebellar artery (OA-PICA) bypass. A 50-year-old woman presented with
      left PICA territory infarction. Left vertebral angiography (VAG) showed occlusion
      of the left VA at the proximal V4 segment. Right VAG revealed that the distal
      part of the left V4 segment with fusiform aneurysmal dilatation was reconstituted
      through vertebrobasilar junction, and the left PICA was the outlet of the blood
      flow from the fusiform aneurysm. Although the patient was treated conservatively,
      enlargement of the left VA fusiform aneurysm was observed 8 months after the
      initial presentation. Considering the potential risks for future stroke or
      bleeding, we performed clip occlusion of the origin of the left PICA, which could
      achieve outflow occlusion of the fusiform aneurysm with preservation of the
      perforators arising around the aneurysm. We created OA-PICA anastomosis for
      revascularization of the distal PICA. The postoperative course was uneventful,
      and the postoperative right VAG revealed occlusion of the fusiform aneurysm.
      Outflow occlusion instead of trapping is an effective surgical option for VA
      fusiform aneurysm to achieve obliterate the aneurysm with preservation of the
      perforator at the blind end.

PMID- 25979425
TI  - Antiphospholipid Syndrome of Late Onset: A Difficult Diagnosis of a Recurrent
      Embolic Stroke.
AB  - A 77-year-old woman with atrial fibrillation (AF) treated with warfarin had a
      cortical left middle cerebral artery (MCA) stroke (October 2009, international
      normalized ratio [INR], 1.6) and a cortical left frontal stroke (October 2011,
      INR, 1.9). Anticoagulation was adjusted. In October 2011, she had a right frontal
      stroke (INR, 2.3). Acetylsalicylic acid (ASA) was temporally added to the
      treatment. In June 2013, she had a left occipital stroke (INR, 2.3). Warfarin was
      changed to rivaroxaban. In August 2013, she had a right occipital stroke. ASA 100
      was added to the treatment. On all occasions, repeated neurovascular studies and
      echocardiography were normal. Diagnoses were cardioembolic stroke. In November
      2013, she was admitted because of a left MCA stroke. A complete blood analysis
      showed the presence of anticardiolipin, anti-b2-glycoprotein antibodies, and
      lupus anticoagulant. Primary antiphospholipid syndrome (APS) was later confirmed.
      APS should be considered in young stroke patients, however is not frequent in
      stroke patients older than 70 years with several cerebrovascular risk factors.
      The existence of AF in our patient with several embolic strokes made the
      cardiembolic etiology likely. Uncommon causes of stroke were not considered
      despite the repetition of the ischemic events. Thus, a wider etiological study
      should be made in all patients with a recurrent stroke regardless of age, such as
      a complete blood analysis including immunology study in order to exclude an APS
      of late onset.

PMID- 25979426
TI  - Gender and psychosocial context as determinants of fibromyalgia symptoms
      (fibromyalgia research criteria) in young adults from the general population.
AB  - OBJECTIVE: To quantify the prevalence of FM (FM research criteria), to describe
      its components-symptom severity score (SSS) and widespread pain index (WPI)-and
      to identify biopsychosocial predictors of the severity of SSS as well as WPI
      using a population-based sample of young adults. METHODS: Participants were part
      of the 21-year-old follow-up of the EPITeen cohort, which was set up during the
      2003-04 school year and comprised subjects born in 1990 attending schools in
      Porto, Portugal (n = 1719, 51.4% women). Data on biopsychosocial characteristics
      were collected, and FM-related information was gathered using the Fibromyalgia
      Survey Questionnaire. Sex-specific multivariate log-binomial regression
      coefficients (beta) and 95% CI were used to quantify the associations between
      adverse biopsychosocial characteristics and high scores in SSS and WPI. RESULTS:
      The overall point-prevalence of FM was 1.0%. Women scored significantly higher in
      SSS and WPI when compared with men. Global psychological distress was strongly
      and significantly associated with high scores in SSS in women and men
      (respectively, low sleep quality, beta = 1.44, 95% CI 1.05, 1.84 and beta = 1.19,
      95% CI 0.78, 1.61; depressive symptoms, beta = 1.64, 95% CI 1.23, 2.06 and beta =
      1.14, 95% CI 0.60, 1.70; eating disorders, beta = 1.17, 95% CI 0.71, 1.63 and
      beta = 1.15, 95% CI 0.52, 1.78). In women, adverse socioeconomic factors were
      predictors of high scores in SSS, whereas in men these contexts were
      significantly associated with high scores in WPI. CONCLUSION: In young adulthood,
      psychological distress was particularly consistent in predicting SSS and may
      become useful as a red flag for the establishment of clinical disease.

PMID- 25979428
TI  - Commentary (Papagikos/Lee): Permanent Prostate Brachytherapy.

PMID- 25979427
TI  - Measured glomerular filtration rate is the goal, but how to measure it?

PMID- 25979429
TI  - The Chromis Experience: An Interpretative Phenomenological Analysis of
      Participants' Experiences of the Chromis Programme.
AB  - This study examined male prisoners' experiences of participating in the Chromis
      programme, which aims to address violent behaviour in offenders with high levels
      of psychopathic traits. Four men who had completed Chromis and moved to new
      locations were purposefully sampled. This provided the opportunity for men to
      discuss their experiences after participating in the full programme and away from
      any influences of the treatment environment. Interview schedules were designed
      using interpretative phenomenological analysis (IPA). Interview transcripts were
      analysed independently by two researchers using IPA who then compared and
      contrasted findings to develop superordinate themes across the group. Four
      superordinate themes resulted. These were "It's me and what I want that matters,"
      Reaping the rewards, "It's treatment itself that makes things hard," and Make or
      break external influences. Across the board, participants benefited at some level
      from Chromis. Participants' experiences highlighted useful information that can
      inform practice with individuals with high levels of psychopathy. The clinical
      implications are discussed. 

PMID- 25979430
TI  - Associations Between Long-Term Gang Membership and Informal Social Control
      Processes, Drug Use, and Delinquent Behavior Among Mexican American Youth.
AB  - Research has found that among juveniles weak ties to informal social control
      entities such as parents, school, and conventional peers increase the probability
      of the initiation and continuation of deviant behaviors such as drug use and
      crime. Given the weak ties of formal social control mechanisms in highly
      disadvantaged communities, informal social control mechanisms are often an
      important deterrent that reduce or moderate engagement in deviant behaviors among
      serious and persistent offenders. This analysis examines the association between
      long-term gang membership and adolescent informal social control processes, drug
      use, and delinquency. This research is based on data from a study of 160 Mexican
      American male gang members between the ages of 16 and 20. Findings suggest that
      among gang members in this context, commonly studied informal control mechanisms
      such as the family and schools do not function to deter long-term gang membership
      that is associated with serious criminal and violent behavior and drug use. The
      implications for future research on desistance or continuation of antisocial
      behavior across the life course are discussed. 

PMID- 25979431
TI  - Treatment Engagement From the Perspective of the Offender.
AB  - A systematic review of the reasons why detained adult offenders fail to attend or
      successfully complete treatment programme(s) was conducted. An initial search of
      the literature identified 2,827 articles, which following evaluation against
      explicit inclusion/exclusion criteria and a quality assessment was reduced to 13
      studies. Extracted data from the 13 studies were synthesised using a qualitative
      approach. Despite the 13 studies being heterogeneous in design, there was
      consensus on the reasons offenders gave for completion/noncompletion of
      treatment. The majority were consistent with the factors outlined in the
      Multifactor Offender Readiness Model (MORM) and included a perceived lack of self
      efficacy, negative perceptions of treatment, staff and peers, an inability to
      regulate emotions, and a lack of perceived choice and control. A lack of
      opportunity to engage in established, professionally run, groups, as well as
      perceived inadequate support from members of staff, was also associated with poor
      engagement and noncompletion of treatment.

PMID- 25979433
TI  - The synaptic recruitment of lipid rafts is dependent on CD19-PI3K module and
      cytoskeleton remodeling molecules.
AB  - Sphingolipid- and cholesterol-rich lipid raft microdomains are important in the
      initiation of BCR signaling. Although it is known that lipid rafts promote the
      coclustering of BCR and Lyn kinase microclusters within the B cell IS, the
      molecular mechanism of the recruitment of lipid rafts into the B cell IS is not
      understood completely. Here, we report that the synaptic recruitment of lipid
      rafts is dependent on the cytoskeleton-remodeling proteins, RhoA and Vav. Such an
      event is also efficiently regulated by motor proteins, myosin IIA and dynein.
      Further evidence suggests the synaptic recruitment of lipid rafts is, by
      principle, an event triggered by BCR signaling molecules and second messenger
      molecules. BCR-activating coreceptor CD19 potently enhances such an event
      depending on its cytoplasmic Tyr421 and Tyr482 residues. The enhancing function
      of the CD19-PI3K module in synaptic recruitment of lipid rafts is also confirmed
      in human peripheral blood B cells. Thus, these results improve our understanding
      of the molecular mechanism of the recruitment of lipid raft microdomains in B
      cell IS. 

PMID- 25979435
TI  - [Primary malignant melanoma of the esophagus: A rare cause of dysphagia].

PMID- 25979434
TI  - Superantigens produced by catheter-associated Staphylococcus aureus elicit
      systemic inflammatory disease in the absence of bacteremia.
AB  - SAgs, produced by Staphylococcus aureus, play a major role in the pathogenesis of
      invasive staphylococcal diseases by inducing potent activation of the immune
      system. However, the role of SAgs, produced by S. aureus, associated with
      indwelling devices or tissues, are not known. Given the prevalence of device
      associated infection with toxigenic S. aureus in clinical settings and the
      potency of SAgs, we hypothesized that continuous exposure to SAgs produced by
      catheter-associated S. aureus could have systemic consequences. To investigate
      these effects, we established a murine in vivo catheter colonization model. One
      centimeter long intravenous catheters were colonized with a clinical S. aureus
      isolate producing SAgs or isogenic S. aureus strains, capable or incapable of
      producing SAg. Catheters were subcutaneously implanted in age-matched HLA-DR3,
      B6, and AE(o) mice lacking MHC class II molecules and euthanized 7 d later. There
      was no evidence of systemic infection. However, in HLA-DR3 transgenic mice, which
      respond robustly to SSAgs, the SSAg-producing, but not the nonproducing strains,
      caused a transient increase in serum cytokine levels and a protracted expansion
      of splenic CD4(+) T cells expressing SSAg-reactive TCR Vbeta8. Lungs, livers, and
      kidneys from these mice showed infiltration with CD4(+) and CD11b(+) cells. These
      findings were absent in B6 and AE(o) mice, which are known to respond poorly to
      SSAgs. Overall, our novel findings suggest that systemic immune activation
      elicited by SAgs, produced by S. aureus colonizing foreign bodies, could have
      clinical consequences in humans. 

PMID- 25979432
TI  - Role of the endothelial surface layer in neutrophil recruitment.
AB  - Neutrophil recruitment in most tissues is limited to postcapillary venules, where
      E- and P-selectins are inducibly expressed by venular endothelial cells. These
      molecules support neutrophil rolling via binding of PSGL-1 and other ligands on
      neutrophils. Selectins extend <= 38 nm above the endothelial plasma membrane, and
      PSGL-1 extends to 50 nm above the neutrophil plasma membrane. However,
      endothelial cells are covered with an ESL composed of glycosaminoglycans that is
      >= 500 nm thick and has measurable resistance against compression. The neutrophil
      surface is also covered with a surface layer. These surface layers would be
      expected to completely shield adhesion molecules; thus, neutrophils should not be
      able to roll and adhere. However, in the cremaster muscle and in many other
      models investigated using intravital microscopy, neutrophils clearly roll, and
      their rolling is easily and quickly induced. This conundrum was thought to be
      resolved by the observation that the induction of selectins is accompanied by ESL
      shedding; however, ESL shedding only partially reduces the ESL thickness (to 200
      nm) and thus is insufficient to expose adhesion molecules. In addition to its
      antiadhesive functions, the ESL also presents neutrophil arrest-inducing
      chemokines. ESL heparan sulfate can also bind L-selectin expressed by the
      neutrophils, which contributes to rolling and arrest. We conclude that ESL has
      both proadhesive and antiadhesive functions. However, most previous studies
      considered either only the proadhesive or only the antiadhesive effects of the
      ESL. An integrated model for the role of the ESL in neutrophil rolling, arrest,
      and transmigration is needed.

PMID- 25979436
TI  - [Ileocolic intussusception as the initial manifestation of primary lymphoma of
      the colon].

PMID- 25979437
TI  - Colonic diverticular disease. Treatment and prevention.
AB  - Diverticular disease represents the most common disease affecting the colon in
      the Western world. Most cases remain asymptomatic, but some others will have
      symptoms or develop complications. The aims of treatment in symptomatic
      uncomplicated diverticular disease are to prevent complications and reduce the
      frequency and intensity of symptoms. Fibre, probiotics, mesalazine, rifaximin and
      their combinations seem to be usually an effective therapy. In the uncomplicated
      diverticulitis, outpatient management is considered the optimal approach in the
      majority of patients, and oral antibiotics remain the mainstay of treatment.
      Admission to hospital and intravenous antibiotic are recommended only when the
      patient is unable to intake food orally, affected by severe comorbidity or does
      not improve. However, inpatient management and intravenous antibiotics are
      necessary in complicated diverticulitis. The role of surgery is also changing.
      Most diverticulitis-associated abscesses can be treated with antibiotics and/or
      percutaneous drainage and emergency surgery is considered only in patients with
      acute peritonitis. Finally, patient related factors, and not the number of
      recurrences, play the most important role in selecting recipients of elective
      surgery to avoid recurrences. 

PMID- 25979438
TI  - Gli1 promotes transforming growth factor-beta1- and epidermal growth factor
      induced epithelial to mesenchymal transition in pancreatic cancer cells.
AB  - BACKGROUND: The Hedgehog signaling pathway and its key target effector Gli1 are
      linked closely to the development of the epithelial to mesenchymal transition
      (EMT) in many cancers. The definite function of Gli1 in regulating the EMT of
      pancreatic cancer (PC), however, is still unclear. METHODS: At the cell and
      tissue levels, we investigated the role of Gli1 in the initiation of EMT in PC
      with and without external stimulus treatments. RESULTS: The immunohistochemistry
      results showed that Gli1 was associated positively with MMP9 but not with E-cad
      or Vimentin. Gli1 expression was associated positively with tumor T (P = .025)
      and Union for International Cancer Control stage (P = .032), whereas MMP9
      expression was associated positively with lymph node metastasis (P = .017) and
      Union for International Cancer Control stage (P = .006). Furthermore, patients
      with Gli1 and MMP9 coexpression had poor overall survival (P = .015). Silencing
      of Gli1 alone without external stimulus had no effect on EMT but inhibited
      transforming growth factor-beta1 (TGFbeta1)- and epidermal growth factor (EGF)
      induced EMT in PANC-1, AsPC-1, and BxPC-3 PC cell lines, along with the
      inhibition of TGFbeta1- and EGF-induced EMT-like cell morphology and invasion,
      down-regulation of E-cad, and up-regulation of MMP9 and Vimentin in those 3 cell
      lines, respectively. CONCLUSION: Gli1 silencing alone has no effect on EMT
      initiation; however, it exerts a protumor role in the aggressive invasion of PC
      cells by promoting TGFbeta1- and EGF-induced EMT.

PMID- 25979439
TI  - The role of facility-based surgical services in addressing the national burden of
      disease in New Zealand: An index of surgical incidence based on country-specific
      disease prevalence.
AB  - BACKGROUND: Surgery is a crucial component of health systems, yet its
      contribution has been difficult to define. We linked national hospital service
      utilization with national epidemiologic data to describe the use of surgical
      procedures in the management of a broad spectrum of conditions. METHODS: We
      compiled International Classification of Diseases-10-Australian Modification
      codes from the New Zealand National Minimum Dataset, 2008-2011. Using primary
      cause of admission, we aggregated hospitalizations into 119 disease states and 22
      disease subcategories of the World Health Organization Global Health Estimate
      (GHE). We queried each hospitalization for any surgical procedure in a binary
      manner to determine the volume of surgery for each disease state. Surgical
      procedures were defined as requiring general or neuroaxial anesthesia. We then
      divided the volume of surgical cases by counts of disease prevalence from the
      Global Burden of Disease Study 2010 to determine annual surgical incidence.
      RESULTS: Between 2008 and 2011, there were 1,108,653 hospital admissions with
      275,570 associated surgical procedures per year. Surgical procedures were
      associated with admissions for all 22 GHE disease subcategories and 116 of 119
      GHE disease states. The sub-categories with the largest surgical case volumes
      were Unintentional Injuries (48,073), Musculoskeletal Diseases (38,030), and
      Digestive Diseases (27,640). Surgical incidence ranged widely by individual
      disease states with the highest in: Other Neurological Conditions, Abortion,
      Appendicitis, Obstructed Labor, and Maternal Sepsis. CONCLUSION: This study
      confirms that surgical care is required across the entire spectrum of GHE disease
      subcategories, illustrating a critical role in health systems. Surgical incidence
      might be useful as an index to estimate the need for surgical procedures in other
      populations.

PMID- 25979440
TI  - Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue
      injury versus hemorrhagic shock.
AB  - INTRODUCTION: Systemic hyperfibrinolysis (accelerated clot degradation) and
      fibrinolysis shutdown (impaired clot degradation) are associated with increased
      mortality compared with physiologic fibrinolysis after trauma. Animal models have
      not reproduced these changes. We hypothesize rodents have a shutdown phenotype
      that require an exogenous profibrinolytic to differentiate mechanisms that
      promote or inhibit fibrinolysis. METHODS: Fibrinolysis resistance was assessed by
      thrombelastography (TEG) using exogenous tissue plasminogen activator (tPA)
      titrations in whole blood. There were 3 experimental groups: (1) tissue injury
      (laparotomy/bowel crush), (2) shock (hemorrhage to mean arterial pressure of 20
      mmHg), and (3) control (arterial cannulation and tracheostomy). Baseline and 30
      minute postintervention blood samples were collected, and assayed with TEG
      challenged with taurocholic acid (TUCA). RESULTS: Rats were resistant to
      exogenous tPA; the percent clot remaining 30 minutes after maximum amplitude
      (CL30) at 150 ng/mL (P = .511) and 300 ng/mL (P = .931) was similar to baseline,
      whereas 600 ng/mL (P = .046) provoked fibrinolysis. Using the TUCA challenge, the
      percent change in CL30 from baseline was increased in tissue injury compared with
      control (P = .048.), whereas CL30 decreased in shock versus control (P = .048).
      tPA increased in the shock group compared with tissue injury (P = .009) and
      control (P = .012). CONCLUSION: Rats have an innate fibrinolysis shutdown
      phenotype. The TEG TUCA challenge is capable of differentiating changes in clot
      stability with rats undergoing different procedures. Tissue injury inhibits
      fibrinolysis, whereas shock promotes tPA-mediated fibrinolysis.

PMID- 25979441
TI  - Predictors of Hospitalization During the First Year of Life among 31999 Tanzanian
      Infants.
AB  - OBJECTIVE: This study explored the risk factors for infant hospitalization in
      urban and peri-urban/rural Tanzania. METHODS: We conducted a prospective cohort
      study examining predictors of hospitalization during the first year of life among
      infants enrolled at birth in a large randomized controlled trial of neonatal
      vitamin A supplementation conducted in urban Dar es Salaam (n = 11,895) and peri
      urban/rural Morogoro region (n = 20,104) in Tanzania. Demographic, socioeconomic,
      environmental and birth outcome predictors of hospitalization were assessed using
      proportional hazard models. RESULTS: The rate of hospitalization was highest
      during the neonatal period in both Dar es Salaam (102/10,000 neonatal-months) and
      Morogoro region (78/10,000 neonatal-months). Hospitalization declined with
      increased age and was lowest for infants 6-12 months of age in both Dar es Salaam
      (11/10,000 infant-months) and Morogoro region (16/10,000 infant-months). In both
      Dar es Salaam and Morogoro region, older maternal age, male sex, low birth weight
      and being small for gestational age were significant predictors of higher risk of
      hospitalization (p < 0.05). Increased wealth and having a flush toilet were
      significantly associated with an increased risk of hospitalization in Morogoro
      region only (p < 0.05). CONCLUSIONS: This study determined high rates of neonatal
      hospitalization in Tanzania. Interventions to increase birth size may decrease
      risk of hospitalization. Equity in access to hospitals for poor rural families in
      Tanzania requires attention.

PMID- 25979442
TI  - A review on the mechanical design elements of ankle rehabilitation robot.
AB  - Ankle rehabilitation robots are developed to enhance ankle strength, flexibility
      and proprioception after injury and to promote motor learning and ankle
      plasticity in patients with drop foot. This article reviews the design elements
      that have been incorporated into the existing robots, for example,
      backdrivability, safety measures and type of actuation. It also discusses
      numerous challenges faced by engineers in designing this robot, including robot
      stability and its dynamic characteristics, universal evaluation criteria to
      assess end-user comfort, safety and training performance and the scientific basis
      on the optimal rehabilitation strategies to improve ankle condition. This article
      can serve as a reference to design robot with better stability and dynamic
      characteristics and good safety measures against internal and external events. It
      can also serve as a guideline for the engineers to report their designs and
      findings.

PMID- 25979443
TI  - Combined magnetic resonance imaging approach for the assessment of in vivo knee
      joint kinematics under full weight-bearing conditions.
AB  - The development of detailed and specific knowledge on the biomechanical behavior
      of loaded knee structures has received increased attention in recent years.
      Stress magnetic resonance imaging techniques have been introduced in previous
      work to study knee kinematics under load conditions. Previous studies captured
      the knee movement either in atypical loading supine positions, or in upright
      positions with help of inclined supporting backrests being insufficient for
      movement capture under full-body weight-bearing conditions. In this work, we used
      a combined magnetic resonance imaging approach for measurement and assessment in
      knee kinematics under full-body weight-bearing in single legged stance. The
      proposed method is based on registration of high-resolution static magnetic
      resonance imaging data acquired in supine position with low-resolution data,
      quasi-static upright-magnetic resonance imaging data acquired in loaded positions
      for different degrees of knee flexion. The proposed method was applied for the
      measurement of tibiofemoral kinematics in 10 healthy volunteers. The combined
      magnetic resonance imaging approach allows the non-invasive measurement of knee
      kinematics in single legged stance and under physiological loading conditions. We
      believe that this method can provide enhanced understanding of the loaded knee
      kinematics.

PMID- 25979444
TI  - Evaluation of add-on methods for bis-acryl composite resin interim restorations.
AB  - STATEMENT OF PROBLEM: Interim restoration materials should allow easy add-on for
      repair and modification; however, bis-acryl composite resins are reported to have
      unfavorable performance in this regard. PURPOSE: The purpose of this study was to
      find a suitably effective add-on method for bis-acryl interim composite resins.
      MATERIAL AND METHODS: A control group with a new type of bis-acryl material added
      to the same bis-acryl disks (n=10) was compared to 9 experimental groups (n=20)
      divided on the basis of their surface conditions: oxygen-inhibited unpolymerized
      layer preserved; ground; ground and treated with a light-polymerizing bonding
      agent, with or without a synthetic polyester film (Mylar) cover strip to control
      oxygen-inhibited unpolymerized layer; with bis-acryl, bis-GMA flowable composite,
      or poly-methyl methacrylate (PMMA) resins as add-on materials. PMMA specimens
      added with PMMA resin served as a parallel control group (n=20). Half of the
      experimental and PMMA control specimens were thermocycled 2000 times at 5 +/-2
      degrees C and 55 +/-2 degrees C. Shear bond strength (SBS) results were then
      compared using 2-way and 1-way ANOVA and a Tukey honest significant difference
      (HSD) test (alpha=.05). RESULTS: No significant differences were found between
      SBS of PMMA and those of bis-acryl controls (21.74 and 17.47 MPa, respectively),
      with all of the experimental groups exhibiting values comparable to the controls
      and unaffected by thermocycling. The highest SBS (35.58 MPa) was obtained with
      the bis-GMA-added group, in which the surface was ground and treated with a
      bonding agent (P<.05). With the bis-acryl resin and bonding agent group,
      additional light polymerizing significantly increased the SBS from 15.58 to 23.80
      MPa (P<.05). CONCLUSIONS: Bis-acryl-based interim material has favorable add-on
      properties, which are improved by additional surface treatment and use of a
      flowable composite resin.

PMID- 25979445
TI  - Labial reduction guide for laminate veneer preparation.
AB  - This article describes a method of fabricating a labial reduction guide for
      laminate veneer preparations by using a digital tire tread depth gauge and
      orthodontic wire. The labial reduction guide can help clinicians to achieve
      accurate reduction of the labial surface. 

PMID- 25979446
TI  - Retrospective analysis of 26 complete-arch implant-supported monolithic zirconia
      prostheses with feldspathic porcelain veneering limited to the facial surface.
AB  - STATEMENT OF PROBLEM: Monolithic zirconia prostheses on teeth or implants have
      been proposed in recent years as a potential treatment. To date, limited data
      regarding the outcomes of these prostheses have been presented and are mainly
      based on limited sample size and short-term follow-up. Data on complete-arch
      monolithic zirconia prostheses are relatively scarce. PURPOSE: The purpose of
      this retrospective study was to evaluate the clinical performances of 26 implant
      supported, complete-arch, monolithic zirconia restorations with facial
      feldspathic porcelain veneers for the rehabilitation of completely edentulous
      patients. MATERIAL AND METHODS: All patients' charts from 2 private practices
      from 2010 to 2013 were reviewed. Patients rehabilitated with a complete-arch
      implant-supported monolithic zirconia prostheses were included in the study.
      Several parameters were recorded so as to evaluate the outcome of these
      rehabilitations: implant survival and success rates, prosthesis survival rate,
      interproximal bone loss, periimplant probing depth, and bleeding on probing. The
      number and type of prosthetic complications were also recorded. Data were
      analyzed with descriptive statistics. RESULTS: Eighteen patients were treated
      with a total of 26 complete-arch fixed prostheses. The mean follow-up time was
      20.9 months (SD 13.6; range, 10 to 36 months). In total, 154 implants were placed
      supporting 309 retainers and pontics. The implant survival rate was 100% and the
      success rate was 94.8%. Mean bone loss was 0.66 mm (SD 0.59 mm). Mean probing
      depth was 3.4 mm (SD 0.92 mm). Bleeding on probing was positive in 19% of probing
      sites. The prosthesis survival rate was 100%. CONCLUSIONS: The results of this
      retrospective evaluation showed that monolithic zirconia restorations with facial
      porcelain veneer provided satisfactory clinical performance and suggest that
      these rehabilitations are a viable treatment option for completely edentulous
      patients.

PMID- 25979447
TI  - CBCT evaluation of buccal bone regeneration in postmenopausal women with and
      without osteopenia or osteoporosis undergoing dental implant therapy.
AB  - STATEMENT OF PROBLEM: Because alveolar bone augmentation in women with
      osteoporosis/osteopenia has an uncertain prognosis, objective and reliable
      methods should be used to study standard surgical approaches. PURPOSE: The
      purpose of this clinical study was to evaluate bone regeneration 9 months after
      bone augmentation and implant placement in postmenopausal women with different
      levels of systemic bone health by using cone beam computed tomography (CBCT) and
      to test proof of concept for this measurement approach. MATERIAL AND METHODS: A
      subset of 14 participants was analyzed in a best practice study of postmenopausal
      women receiving dental implants and simultaneous horizontal ridge augmentation.
      Women were categorized as osteopenic/osteoporotic or normal based on the results
      of preoperative dual-energy x-ray absorptiometry. All implant study sites
      received a particulate graft and/or buccal plate expansion. The study sites were
      evaluated with CBCT preoperatively, immediately postoperatively, and 9 months
      postoperatively. Nonparametric statistics were used for all analyses. The related
      samples Wilcoxon signed rank test was used to assess the differences in bone
      width between time points (alpha=.05 for all tests). RESULTS: After 9 months, 13
      out of 14 participants showed increased bone width compared to the preoperative
      baseline measurements. The increase was statistically significant for the
      participants with osteoporosis/osteopenia (P=.007), but not for those with normal
      bone health (P=.066). The CBCT scans showed that mineralized tissue buccal to the
      implant surface had the radiographic appearance of mature bone. CONCLUSIONS: CBCT
      showed evidence of bone regeneration, with an increase in alveolar ridge width in
      postmenopausal osteopenic/osteoporotic women subsequent to surgical
      reconstruction.

PMID- 25979448
TI  - Comparison of the Kois Dento-Facial Analyzer System with an earbow for mounting a
      maxillary cast.
AB  - STATEMENT OF PROBLEM: The Kois Dento-Facial Analyzer System (KDFA) is used by
      clinicians to mount maxillary casts and evaluate and treat patients. Limited
      information is available for understanding whether the KDFA should be considered
      as an alternative to an earbow. PURPOSE: The purpose of this study was to
      evaluate maxillary casts mounted using the KDFA with casts mounted using
      Panadent's Pana-Mount Facebow (PMF). Both articulation methods were compared
      against a lateral cephalometric radiograph. MATERIAL AND METHODS: Fifteen dried
      human skulls were used. Lateral cephalometric radiographs and 2 maxillary
      impressions were made of each skull. One cast from each skull was mounted on an
      articulator by means of the KDFA and the other by using the PMF. A standardized
      photograph of each articulation was made, and the distance from the articular
      center to the incisal edge position and the occlusal plane angle were measured.
      The distance from condylar center to the incisal edge and the occlusal plane
      angle were measured from cephalometric radiographs. Finally, the 3-dimensional
      position of each articulation was determined with a Panadent CPI-III. A
      randomized complete block design analysis of variance (RCBD) and post hoc tests
      (Tukey-Kramer HSD) (alpha=.05) were used to evaluate the occlusal plane angle and
      axis-central incisor distance. A paired 2-sample t test for means (alpha=.05) was
      used to compare the X, Y, and Z distance at the right and left condyle. RESULTS:
      The KDFA and PMF mounted the maxillary cast in a position that was not
      statistically different from the skull when comparing the occlusal plane angle
      (P=.165). Both the KDFA and the PMF located the maxillary central incisor edge
      position in a significantly different position compared with the skull (P=.001)
      but were not significantly different from each other. The 3-dimensional location
      of the maxillary casts varied at the condyles by approximately 9 to 10.3 mm.
      CONCLUSION: The KDFA mounted the maxillary cast in a position that was not
      statistically different from the PMF when comparing the incisal edge position and
      the occlusal plane angle. Both the KDFA and the PMF located the maxillary incisal
      edge position in a significantly different position compared with the anatomic
      position on dried human skulls.

PMID- 25979449
TI  - Cobalt-chromium alloys in dentistry: An evaluation of metal ion release.
AB  - STATEMENT OF PROBLEM: Metal ions released into the oral cavity from dental
      prosthesis alloys may damage the cellular metabolism or proliferation and cause
      hypersensitivity or allergies. The oral cavity environment is particularly prone
      to corrosion due to saliva, microorganisms, and pH variations. PURPOSE: The
      purpose of this in vitro study was to evaluate the ion release of chromium,
      cobalt, and iron from the Co-Cr alloys used for traditionally cast and computer
      aided design/computer-aided manufacturing dental devices after interaction with
      oral bacteria and different pH conditions. MATERIAL AND METHODS: All specimens
      were prepared from currently available alloys, polished, and immersed in 3
      different pH media (artificial saliva [pH 2.3] and 6.5% and 0.9% saline solution
      [pH 7.1]). Specimens were also incubated in the presence of the bacterium
      Eikenella corrodens. Solutions were analyzed with an atomic absorption
      spectrometer after 15 and 30 days in the chemical corrosion test and 30 days in
      the biocorrosion test to detect ions released in different solutions. An ANOVA
      test was used to evaluate statistically significant differences among the
      percentages of metal corrosion ion release values. RESULTS: The greatest amount
      of element release was seen after 30 days: 4.964 ppm of casting alloy, 2.642 ppm
      of milling alloy, and 2.351 ppm of laser metal sintering. CONCLUSIONS: With the
      exception of casting alloy under acidic conditions, no significant differences
      were found, even after exposure to bacteria.

PMID- 25979450
TI  - Association between MDM2 SNP309 and skin cancer: A meta-analysis of case-control
      studies.

PMID- 25979451
TI  - Superficial epidermolytic ichthyosis caused by a novel KRT2 mutation.

PMID- 25979452
TI  - [Day care surgery for laparoscopic gynecologic surgery: What can be done?].
AB  - OBJECTIVES: To study feasibility of day care surgery for laparoscopy for adnexial
      pathology, infertility treatment or exploration and to research influencing
      factors. MATERIAL AND METHOD: Women who beneficiate of laparoscopy for adnexial
      pathology, infertility treatment or exploration and to research influencing
      factors were included between 1st January 2010 and 30th June 2012 in this
      monocentric retrospective study. RESULTS: Four hundred women were included. Day
      care surgery was possible in 63% of cases. A switch to conventional
      hospitalization was required for 17% of the women planned for day care surgery.
      The rate of a second hospitalization in the month following day care procedure
      was 1% with 0.4% of second surgery for complications. Influencing factors for day
      care surgery are age, surgeon and time of the surgery. The global satisfaction
      rate of women was 98%. CONCLUSION: Day care surgery is feasible for women who
      beneficiate of laparoscopy for adnexial pathology, infertility treatment or
      exploration. Second hospitalization or surgery for complications is very rare.

PMID- 25979453
TI  - [Obstetrical prognosis of breech presentations with premature rupture of
      membranes at term].
AB  - OBJECTIVES: Breech delivery is still a controversial situation in literature.
      Added complexity exists when breech presentations are associated with premature
      rupture of membranes (PROM) as such cases are conventionally excluded in studies
      dealing with PROM and are often indications for elective caesarean section. Thus,
      the objective of this study was to evaluate the obstetrical prognosis of breech
      presentations after PROM at term. MATERIALS AND METHODS: We conducted a
      retrospective observational study at the Besancon University Medical Centre,
      between 1(st) January 2008 and 31(th) December 2012. Two groups of patients with
      breech presentations at term were constituted according to the existence or not
      of a PROM. The primary endpoint was the delivery mode: caesarean section or
      vaginal. Other endpoints were maternal characteristics, type of onset of labour
      and neonatal criterias. RESULTS: Two hundred and nine patients were included. In
      the control group, 67.9 % of vaginal deliveries occurred versus 60 % in the group
      with PROM (P=0.25). No difference was found on neonatal criterias such as pH,
      lactate and the Apgar score at 5 minutes. CONCLUSION: PROM at term in breech
      presentation doesn't seem to change the obstetrical prognosis and should
      therefore not be a systematic indication for elective caesarean section.

PMID- 25979454
TI  - Centers for Disease Control and Prevention: protecting the private good?

PMID- 25979456
TI  - Vagal modulation of pre-inspiratory activity in hypoglossal discharge in the
      decerebrate rat.
AB  - Respiration consists of three phases--inspiration (I), post-inspiration (post-I),
      and late expiration (E2). Pre-I is a subphase occurring at the end of E2.
      Hypoglossal (XII) discharge contains I and occasionally pre-I activity.
      Functionally, XII pre-I underlies tongue muscle contraction and expansion of the
      upper airway, causing a decrease in airway resistance in anticipation of the
      succeeding inspiratory effort. It has been shown that vagotomy causes an increase
      in pre-I activity in XII in anesthetized animals. Also, in anesthetized
      artificially-ventilated animals, XII onset is synchronized with that of
      inspiratory phrenic nerve (PhN) activity. Therefore, we sought to systematically
      test the hypothesis that XII pre-I is present in vagus-intact unanesthetized
      decerebrate animals and vagal afferents negatively modulate XII pre-I discharge
      in decerebrate rats, in the absence of confounding anesthesia. Experiments were
      performed on seven Sprague-Dawley unanesthetized decerebrate adult male rats and
      bilateral PhN and XII recordings performed. In three animals, vagotomy was
      performed during PhN recordings and one animal was vagotomized during initial
      surgical preparation prior to recordings. In vagus-intact animals, XII pre-I
      duration averaged 12.4 ms. Vagotomy was associated with greater XII pre-I
      duration, expressed in absolute time (89.5 vs. 12.4 ms; p<0.01) as well as
      relative to the XII bursting period (18.9 vs. 3.4%; p<0.01). Vagal
      deafferentation was also associated with a larger relative amplitude of the pre-I
      XII activity relative to total XII discharge (12.4 vs. 2.1%; p<0.01). We conclude
      that pre-I discharge is present in vagus-intact artificially-ventilated
      unanesthetized decerebrate animals and is negatively modulated by vagal
      afferents.

PMID- 25979455
TI  - Microwave assisted efficient synthesis of diphenyl substituted pyrazoles using
      PEG-600 as solvent - A green approach.
AB  - A conventional and microwave assisted efficient synthesis of diphenyl substituted
      pyrazole using PEG 600 as green solvent has been described. A relatively shorter
      reaction time with excellent yield of the piperidine mediated protocol has been
      attracted economically attractive and eco-friendly. All newly synthesized
      compounds were characterized by standard spectroscopic techniques viz., UV
      visible, FT-IR, (1)H-NMR and Mass spectra. The anti-microbial activities of
      compounds have also been tested using Minimum Inhibitory Concentration (MIC)
      method with two different microorganisms Staphylococcus aureus (MTCC3381) and
      Escherichia coli (MTCC739). The results of the antimicrobial activity revealed
      that the diphenyl substituted pyrazole derivatives have nice inhibiting nature
      against both types of bacteria of present investigation than corresponding
      chalcones. Since, the work has been focused on green chemical approach towards
      the synthesis, this protocol may be recommended for eco-friendly applications. 

PMID- 25979457
TI  - Nurses' Experiences of Patients with Substance-Use Disorder in Pain: A
      Phenomenological Study.
AB  - Patients with substance-use disorder and pain are at risk of having their pain
      underestimated and undertreated. Unrelieved pain can exacerbate characteristics
      that are believed to be 'drug-seeking' and in turn, perceived drug-seeking
      behavior can contribute to a patient being stigmatized and labeled 'difficult'.
      Previous literature has indicated that negative attitudes towards patients with
      substance-use disorder may affect their pain management but little is known about
      the specific barriers. This study explored nurses' experiences of working with
      patients with substance-use disorder in pain, providing an in-depth insight into
      their perspective. Descriptive phenomenology was employed as a framework for
      conducting semi-structured interviews to reveal the experiences of registered
      nurses. A convenience sample of registered nurses from a variety of clinical
      backgrounds were recruited and interviewed. This rich data was analyzed according
      to Giorgi's five-stage approach. Participants described feelings of powerlessness
      and frustration due to patient non-compliance, discrepancies in patient
      management amongst team members and external pressures effecting pain management.
      Participants described characteristics believed to be common, including
      psychosocial factors such as complex social backgrounds or mental health issues.
      Nurses' education and support needs were identified. Stereotyping and stigmatism
      were found to potentially still exist, yet there was also a general awareness of
      some specific clinical issues such as opioid tolerance and opioid-induced
      hyperalgesia. Further emphasis is required on interprofessional education and
      communication to improve patient management, alongside an appreciation of
      patient's rights facilitated by a concordance model of care. 

PMID- 25979458
TI  - The Importance of Written and Verbal Information on Pain Treatment for Patients
      Undergoing Surgical Interventions.
AB  - Patients who undergo a surgical intervention require information in the
      preoperative phase. Few qualitative studies are available that illuminate the
      importance of preoperative information for patients' experiences of postoperative
      pain management. The aim of this study was to examine patients' perceptions of
      preoperative information about pain treatment as well as its importance for the
      way pain was managed in the postoperative phase. A descriptive, qualitative study
      using individual interviews was performed. Content analysis was employed to
      analyze individual interviews with 18 patients who had undergone total hip or
      knee joint plastic surgery. Every second participant received verbal information
      on pain treatment in the standard way at the preoperative discussion, whereas the
      others were also provided with written information. The interviews took place in
      a public hospital, on the second or third postoperative day, between September
      and November 2010. The study revealed that a combination of written and verbal
      information on pain relief was perceived as valuable by the patients. Four main
      categories were identified: The form of information; the content of the
      information; the patients' experience of postoperative pain relief, and factors
      that influenced the patients' experience of pain relief. The theme
      "Participation" emerged from the latent content. Preoperative information on pain
      relief facilitated increased patient participation. Health care professionals
      often aim to ensure that patients participate in the care, but the latter
      sometimes lack the desire, strength, or ability to become involved. 

PMID- 25979459
TI  - Personalized diagnosis of medulloblastoma subtypes across patients and model
      systems.
AB  - Molecular subtyping is instrumental towards selection of model systems for
      fundamental research in tumor pathogenesis, and clinical patient assessment.
      Medulloblastoma (MB) is a highly heterogeneous, malignant brain tumor that is the
      most common cause of cancer-related deaths in children. Current MB classification
      schemes require large sample sizes, and standard reference samples, for subtype
      predictions. Such approaches are impractical in clinical settings with limited
      tumor biopsies, and unsuitable for model system predictions where standard
      reference samples are unavailable. Our developed Medullo-Model To Subtype (MM2S)
      classifier stratifies single MB gene expression profiles without reference
      samples or replicates. Our pathway-centric approach facilitates subtype
      predictions of patient samples, and model systems including cell lines and mouse
      models. MM2S demonstrates >96% accuracy for patients of well-characterized normal
      cerebellum, WNT, or SHH subtypes, and the less-characterized Group 4 (86%) and
      Group 3 (78.2%). MM2S also enables classification of MB cell lines and mouse
      models into their human counterparts. 

PMID- 25979460
TI  - Integrated analysis of mRNA and miRNA expression in response to interleukin-6 in
      hepatocytes.
AB  - The expression of plasma proteins changes dramatically as a result of cytokine
      induction, particularly interleukin-6, and their levels are used as clinical
      markers of inflammation. miRNAs are important regulators of gene expression and
      play significant roles in many inflammatory diseases and processes. The
      interactions between miRNAs and the genes that they regulate during the acute
      phase response have not been investigated. We examined the effects of IL-6
      stimulation on the transcriptome and miRNome of human and mouse primary
      hepatocytes and the HepG2 cell line. Using an integrated analysis, we identified
      differentially expressed miRNAs whose seed sequences are significantly enriched
      in the 3' untranslated regions of differentially expressed genes, many of which
      are involved in inflammation-related pathways. Our finding that certain miRNAs
      may de-repress critical acute phase proteins within acute timeframes has
      important biological and clinical implications. 

PMID- 25979461
TI  - Low-dose hypobaric bupivacaine spinal lateral position anesthesia for hip surgery
      in high-risk surgical patients.

PMID- 25979462
TI  - Tourniquet use during ankle surgery leads to increased postoperative opioid use.
AB  - STUDY OBJECTIVE: Ankle surgery is often done using a tourniquet.
      Ischemia/reperfusion injury caused by the tourniquet may increase postoperative
      pain. The study objective was to investigate the amount of opioids given to
      patients after ankle surgery with and without tourniquet. DESIGN: We did a cohort
      study based on data from patient's records between January 2008 and December
      2011. SETTING: Information is gathered from operating room, postanesthetic care
      unit, and surgical ward in a university hospital. PATIENTS: We identified
      patients undergoing reconstructive ankle fracture surgery from hospital records.
      We excluded multiple fractures of the same extremity, major trauma, reoperations,
      arthrodesis of the ankle joint, and missing data on tourniquet use. We included
      603 patients. INTERVENTIONS: For each patient, we registered for how long
      (minutes) the tourniquet was inflated. MEASUREMENTS: Main outcome was opioid use
      during first 24 hours postoperatively (in equipotent intravenous morphine doses).
      Secondary outcomes were the peak pain on a verbal rating scale, time in
      postanesthetic care unit, and additional antiemetic medicine. We performed
      multiple regression to analyze the primary outcome. MAIN RESULTS: Three hundred
      fifty-eight patients underwent surgery with tourniquet. There was a correlation
      between tourniquet time and postoperative opioid use (P value = .001) after
      controlling for confounders. The slope of the correlation was 0.04 mg/min (95%
      confidence interval, 0.02-0.07), which means there is an increase in
      postoperative opioid use by 0.43 mg for every 10 minutes of tourniquet time.
      CONCLUSION: We found an increase in postoperative opioid consumption correlated
      to tourniquet use. Possible preventive measures with antioxidant treatment to
      prevent ischemia/reperfusion injury should be investigated.

PMID- 25979463
TI  - Efficient production of FAM19A4, a novel potential cytokine, in a stable
      optimized CHO-S cell system.
AB  - FAM19A4 is a novel potential cytokine identified by our group, which can
      chemoattract macrophages, promote phagocytosis against zymosan and increase
      reactive oxygen species (ROS) release. To further explore the role of FAM19A4 in
      immune system, abundant recombinant protein with high quality is indispensable.
      For efficient production of FAM19A4, we used an improved CHO-S cell expression
      system on the basis of pMH3 vector containing GC-rich regions which were novel
      ubiquitous chromatin opening elements (UCOEs). We selected CHO-S cells stably
      expressing FAM19A4 with G418 and screened cell clones with high level of FAM19A4
      expression by immune blot and his-ELISA, adapted cell clones to serum-free
      suspension culture. Afterwards, we obtained the highest FAM19A4 expressing cell
      clone (2#) through 40 ml batch culture. We optimized the fed-batch culture
      condition and discovered the final cell viability was critical for FAM19A4
      production successfully. Then we scaled 2# clone up to 3 L in fed-batch culture
      and obtained 22 mg (7.33 mg/L, averagely) endotoxin free FAM19A4 protein with
      purity over 95% using Ni affinity chromatography and size exclusion
      chromatography. The final yield was increased 3.6-folds compared to that of our
      previously reported transient system. Besides, the purified FAM19A4 protein
      showed chemotactic activity on macrophages. In summary, we developed a stable
      optimized fed-batch CHO-S cell system to produce FAM19A4, which not only provided
      sufficient bioactive FAM19A4 protein for further research but also offered an
      efficient strategy for other recombinant protein production.

PMID- 25979465
TI  - Characterization of the LysR-type transcriptional regulator YcjZ-like from
      Xylella fastidiosa overexpressed in Escherichia coli.
AB  - The Xylella fastidiosa 9a5c strain is a xylem-limited phytopathogen that is the
      causal agent of citrus variegated chlorosis (CVC). This bacterium is able to form
      a biofilm and occlude the xylem vessels of susceptible plants, which leads to
      significant agricultural and economic losses. Biofilms are associated with
      bacterial pathogenicity because they are very resistant to antibiotics and other
      metal-based chemicals that are used in agriculture. The X. fastidiosa YcjZ-like
      (XfYcjZ-like) protein belongs to the LysR-type transcriptional regulator (LTTR)
      family and is involved in various cellular functions that range from quorum
      sensing to bacterial survival. In the present study, we report the cloning,
      expression and purification of XfYcjZ-like, which was overexpressed in
      Escherichia coli. The secondary folding of the recombinant and purified protein
      was assessed by circular dichroism, which revealed that XfYcjZ-like contains a
      typical alpha/beta fold. An initial hydrodynamic characterization showed that
      XfYcjZ-like is a globular tetramer in solution. In addition, using a polyclonal
      antibody against XfYcjZ-like, we assessed the expression profile of this protein
      during the different developmental phases of X. fastidiosa in in vitro cultivated
      biofilm cells and demonstrated that XfYcjZ-like is upregulated in planktonic
      cells in response to a copper shock treatment. Finally, the ability of XfYcjZ
      like to interact with its own predicted promoter was confirmed in vitro, which is
      a typical feature of LysR. Taken together, our findings indicated that the XfYcjZ
      like protein is involved in both the organization of the architecture and the
      maturation of the bacterial biofilm and that it is responsive to oxidative
      stress. 

PMID- 25979464
TI  - Purification and biochemical characterization of the ATP synthase from
      Heliobacterium modesticaldum.
AB  - Heliobacterium modesticaldum is an anaerobic photosynthetic bacterium that grows
      optimally at pH 6-7 and 52 degrees C and is the only phototrophic member of the
      Firmicutes phylum family (gram-positive bacteria with low GC content). The ATP
      synthase of H. modesticaldum was isolated and characterized at the biochemical
      and biophysical levels. The isolated holoenzyme exhibited the subunit patterns of
      F-type ATP synthases containing a 5-subunit hydrophilic F1 subcomplex and a 3
      subunit hydrophobic F0 subcomplex. ATP hydrolysis by the isolated HF1F0 ATP
      synthase was successfully detected after pretreatment with different detergents
      by an in-gel ATPase activity assay, which showed that the highest activity was
      detected in the presence of mild detergents such as LDAO; moreover, high
      catalytic activity in the gel was already detected after the initial incubation
      period of 0.5h. In contrast, HF1F0 showed extremely low ATPase activity in
      harsher detergents such as TODC. The isolated fully functional enzyme will form
      the basis for future structural studies. 

PMID- 25979466
TI  - Erythrocyte polyunsaturated fatty acid levels in young people at ultra-high risk
      for psychotic disorder and healthy adolescent controls.
AB  - Erythrocyte polyunsaturated fatty acid (PUFA) levels from individuals at ultra
      high risk (UHR) for psychosis (n = 80) were compared to existing data from
      healthy controls (n = 142). Results demonstrated PUFA deficits (alpha-linolenic
      acid, eicosapentanoic acid, all omega-6 PUFAs) for the UHR group. Findings
      provide a rationale for PUFA based interventions in emerging psychosis.

PMID- 25979467
TI  - Gender determines cortisol and alpha-amylase responses to acute physical and
      psychosocial stress in patients with borderline personality disorder.
AB  - Borderline personality disorder (BPD) is characterized by affective instability,
      unstable relationships, and identity disturbance. We measured salivary alpha
      amylase (sAA) and salivary cortisol levels in all participants during exposure to
      the Trier Social Stress Test (TSST) and an electric stimulation stress. Seventy
      two BPD patients were compared with 377 age- and gender- matched controls. The
      State and Trait versions of the Spielberger Anxiety Inventory test (STAI-S and
      STAI-T, respectively), the Profile of Mood State (POMS) tests, and the Beck
      Depression Inventory (BDI), the Depression and Anxiety Cognition Scale (DACS)
      were administered to participants before electrical stimulation. Following TSST
      exposure, salivary cortisol levels significantly decreased in female patients and
      significantly increased in male patients compared with controls. POMS tension
      anxiety, depression-dejection, anger-hostility, fatigue, and confusion scores
      were significantly increased in BPD patients compared with controls. In contrast,
      vigor scores were significantly decreased in BPD patients relative to controls.
      Furthermore, STAI-T and STAI-S anxiety scores and BDI scores were significantly
      increased in BPD patient compared with controls. DACS scores were significantly
      increased in BPD patient compared with controls. Different stressors (e.g.,
      psychological or physical) induced different responses in the HPA and SAM systems
      in female or male BPD patients. 

PMID- 25979469
TI  - Complex Systems Are More than the Sum of Their Parts: Using Integration to
      Understand Performance, Biomechanics, and Diversity.
AB  - Organisms are comprised of many interacting parts, and an increased number or
      specialization of those parts leads to greater complexity and the necessity for
      increased integration (the ability of those parts to perform together and
      maintain a functioning organism). Although this idea is widely recognized among
      biologists, organisms are more tangibly studied when those parts are considered
      independently. This reductionist approach has successfully advanced our
      understanding of organisms' performance. However, performance of one system might
      (or might not) be dependent on performance of another system to achieve a
      relevant outcome, and the mechanism of this dependence is poorly understood. We
      synthesize the concepts of complexity and integration and discuss their
      application in a biomechanical context. Capture of prey by predatory fishes is
      used as an example to highlight the application of these ideas. We provide a
      theoretical framework for future hypotheses of integration and predict an
      "integration space" for fishes that is then populated with data extracted from
      the literature. Additionally, using the kinematics of prey-capture in two species
      of sculpin (Scorpaeniformes: Cottidae), we show that species exhibit multivariate
      integration in distinct ways, and that these differences add additional insight
      into ecological divergence that would not be apparent by considering systems
      independently. Finally, we discuss new insights into organismal performance
      gained through the study of integration as an emergent property of kinematic
      systems working together during a common task. Integration is rarely the trait of
      interest, but we show that future work should adopt a more holistic approach to
      understand why and how animals perform complex behaviors. 

PMID- 25979470
TI  - Clinical implications of leukocyte infiltration at the choroid plexus in
      (neuro)inflammatory disorders.
AB  - The choroid plexus (CP) is a highly vascularized organ located in the brain
      ventricles and contains a single epithelial cell layer forming the blood
      cerebrospinal fluid barrier (BCSFB). This barrier is crucial for immune
      surveillance in health and is an underestimated gate for entry of immune cells
      during numerous inflammatory disorders. Several of these disorders are
      accompanied by disturbance of the BCSFB and increased leukocyte infiltration,
      which affects neuroinflammation. Understanding the mechanism of immune cell entry
      at the CP might lead to identification of new therapeutic targets. Here, we focus
      on current knowledge of leukocyte infiltration at the CP in inflammatory
      conditions and its therapeutic implications. 

PMID- 25979471
TI  - Repeat- and error-aware comparison of deletions.
AB  - MOTIVATION: The number of reported genetic variants is rapidly growing, empowered
      by ever faster accumulation of next-generation sequencing data. A major issue is
      comparability. Standards that address the combined problem of inaccurately
      predicted breakpoints and repeat-induced ambiguities are missing. This decisively
      lowers the quality of 'consensus' callsets and hampers the removal of duplicate
      entries in variant databases, which can have deleterious effects in downstream
      analyses. RESULTS: We introduce a sound framework for comparison of deletions
      that captures both tool-induced inaccuracies and repeat-induced ambiguities. We
      present a maximum matching algorithm that outputs virtual duplicates among two
      sets of predictions/annotations. We demonstrate that our approach is clearly
      superior over ad hoc criteria, like overlap, and that it can reduce the
      redundancy among callsets substantially. We also identify large amounts of
      duplicate entries in the Database of Genomic Variants, which points out the
      immediate relevance of our approach. AVAILABILITY AND IMPLEMENTATION:
      Implementation is open source and available from
      https://bitbucket.org/readdi/readdi CONTACT: roland.wittler@uni-bielefeld.de or
      t.marschall@mpi-inf.mpg.de SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25979472
TI  - Seq2pathway: an R/Bioconductor package for pathway analysis of next-generation
      sequencing data.
AB  - Seq2pathway is an R/Python wrapper for pathway (or functional gene-set) analysis
      of genomic loci, adapted for advances in genome research. Seq2pathway associates
      the biological significance of genomic loci with their target transcripts and
      then summarizes the quantified values on the gene-level into pathway scores. It
      is designed to isolate systematic disturbances and common biological
      underpinnings from next-generation sequencing (NGS) data. Seq2pathway offers
      Bioconductor users enhanced capability in discovering collective pathway effects
      caused by both coding genes and cis-regulation of non-coding elements.
      AVAILABILITY AND IMPLEMENTATION: The package is freely available at
      http://www.bioconductor.org/packages/release/bioc/html/seq2pathway.html. CONTACT:
      xyang2@uchicago.edu SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 25979473
TI  - SpeeDB: fast structural protein searches.
AB  - MOTIVATION: Interactions between amino acids are important determinants of the
      structure, stability and function of proteins. Several tools have been developed
      for the identification and analysis of such interactions in proteins based on the
      extensive studies carried out on high-resolution structures from Protein Data
      Bank (PDB). Although these tools allow users to identify and analyze
      interactions, analysis can only be performed on one structure at a time. This
      makes it difficult and time consuming to study the significance of these
      interactions on a large scale. RESULTS: SpeeDB is a web-based tool for the
      identification of protein structures based on structural properties. SpeeDB
      queries are executed on all structures in the PDB at once, quickly enough for
      interactive use. SpeeDB includes standard queries based on published criteria for
      identifying various structures: disulphide bonds, catalytic triads and aromatic
      aromatic, sulphur-aromatic, cation-pi and ionic interactions. Users can also
      construct custom queries in the user interface without any programming. Results
      can be downloaded in a Comma Separated Value (CSV) format for further analysis
      with other tools. Case studies presented in this article demonstrate how SpeeDB
      can be used to answer various biological questions. Analysis of human proteases
      revealed that disulphide bonds are the predominant type of interaction and are
      located close to the active site, where they promote substrate specificity. When
      comparing the two homologous G protein-coupled receptors and the two protein
      kinase paralogs analyzed, the differences in the types of interactions
      responsible for stability accounts for the differences in specificity and
      functionality of the structures. AVAILABILITY AND IMPLEMENTATION: SpeeDB is
      available at http://www.parallelcomputing.ca as a web service. CONTACT:
      d@drobilla.net SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 25979468
TI  - An overview of microRNAs.
AB  - The discovery of the first microRNA (miRNA) over 20 years ago has ushered in a
      new era in molecular biology. There are now over 2000 miRNAs that have been
      discovered in humans and it is believed that they collectively regulate one third
      of the genes in the genome. miRNAs have been linked to many human diseases and
      are being pursued as clinical diagnostics and as therapeutic targets. This review
      presents an overview of the miRNA pathway, including biogenesis routes,
      biological roles, and clinical approaches.

PMID- 25979474
TI  - WGE: a CRISPR database for genome engineering.
AB  - The rapid development of CRISPR-Cas9 mediated genome editing techniques has given
      rise to a number of online and stand-alone tools to find and score CRISPR sites
      for whole genomes. Here we describe the Wellcome Trust Sanger Institute Genome
      Editing database (WGE), which uses novel methods to compute, visualize and select
      optimal CRISPR sites in a genome browser environment. The WGE database currently
      stores single and paired CRISPR sites and pre-calculated off-target information
      for CRISPRs located in the mouse and human exomes. Scoring and display of off
      target sites is simple, and intuitive, and filters can be applied to identify
      high-quality CRISPR sites rapidly. WGE also provides a tool for the design and
      display of gene targeting vectors in the same genome browser, along with gene
      models, protein translation and variation tracks. WGE is open, extensible and can
      be set up to compute and present CRISPR sites for any genome. AVAILABILITY AND
      IMPLEMENTATION: The WGE database is freely available at www.sanger.ac.uk/htgt/wge
      CONTACT: : vvi@sanger.ac.uk or skarnes@sanger.ac.uk SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 25979475
TI  - Likelihood-based complex trait association testing for arbitrary depth sequencing
      data.
AB  - In next generation sequencing (NGS)-based genetic studies, researchers typically
      perform genotype calling first and then apply standard genotype-based methods for
      association testing. However, such a two-step approach ignores genotype calling
      uncertainty in the association testing step and may incur power loss and/or
      inflated type-I error. In the recent literature, a few robust and efficient
      likelihood based methods including both likelihood ratio test (LRT) and score
      test have been proposed to carry out association testing without intermediate
      genotype calling. These methods take genotype calling uncertainty into account by
      directly incorporating genotype likelihood function (GLF) of NGS data into
      association analysis. However, existing LRT methods are computationally demanding
      or do not allow covariate adjustment; while existing score tests are not
      applicable to markers with low minor allele frequency (MAF). We provide an LRT
      allowing flexible covariate adjustment, develop a statistically more powerful
      score test and propose a combination strategy (UNC combo) to leverage the
      advantages of both tests. We have carried out extensive simulations to evaluate
      the performance of our proposed LRT and score test. Simulations and real data
      analysis demonstrate the advantages of our proposed combination strategy: it
      offers a satisfactory trade-off in terms of computational efficiency,
      applicability (accommodating both common variants and variants with low MAF) and
      statistical power, particularly for the analysis of quantitative trait where the
      power gain can be up to ~60% when the causal variant is of low frequency (MAF <
      0.01). AVAILABILITY AND IMPLEMENTATION: UNC combo and the associated R files,
      including documentation, examples, are available at
      http://www.unc.edu/~yunmli/UNCcombo/ CONTACT: yunli@med.unc.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25979476
TI  - CoRegNet: reconstruction and integrated analysis of co-regulatory networks.
AB  - CoRegNet is an R/Bioconductor package to analyze large-scale transcriptomic data
      by highlighting sets of co-regulators. Based on a transcriptomic dataset,
      CoRegNet can be used to: reconstruct a large-scale co-regulatory network,
      integrate regulation evidences such as transcription factor binding sites and
      ChIP data, estimate sample-specific regulator activity, identify cooperative
      transcription factors and analyze the sample-specific combinations of active
      regulators through an interactive visualization tool. In this study CoRegNet was
      used to identify driver regulators of bladder cancer. AVAILABILITY: CoRegNet is
      available at http://bioconductor.org/packages/CoRegNet CONTACT:
      remy.nicolle@issb.genopole.fr or mohamed.elati@issb.genopole.fr SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25979477
TI  - Message from ISCB: Outstanding contributions to ISCB award.

PMID- 25979478
TI  - Effects of annual and interannual environmental variability on soil fungi
      associated with an old-growth, temperate hardwood forest.
AB  - Seasonal and interannual variability in temperature, precipitation and chemical
      resources may regulate fungal community structure in forests but the effect of
      such variability is still poorly understood. In this study, I examined changes in
      fungal communities over two years and how these changes were correlated to
      natural variation in soil conditions. Soil cores were collected every month for
      three years from permanent plots established in an old-growth hardwood forest,
      and molecular methods were used to detect fungal species. Species richness and
      diversity were not consistent between years with richness and diversity
      significantly affected by season in one year but significantly affected by depth
      in the other year. These differences were associated with variation in late
      winter snow cover. Fungal communities significantly varied by plot location,
      season and depth and differences were consistent between years but fungal species
      within the community were not consistent in their seasonality or in their
      preference for certain soil depths. Some fungal species, however, were found to
      be consistently correlated with soil chemistry across sampled years. These
      results suggest that fungal community changes reflect the behavior of the
      individual species within the community pool and how those species respond to
      local resource availability.

PMID- 25979479
TI  - The contribution of organised sports to physical activity in Australia: Results
      and directions from the Active Healthy Kids Australia 2014 Report Card on
      physical activity for children and young people.
AB  - Youth participation in organised sport and physical activity is important for
      healthy development, growth and wellbeing. In 2014, Active Healthy Kids Australia
      released its inaugural Report Card on Physical Activity for Children and Young
      People, which synthesised the best available national- and state-level data for
      children and young people (<18 years). This paper provides a more detailed
      examination of the evidence informing the grade for Organised Sport from the 2014
      Report Card, compares Australia's Organised Sport grade with other countries,
      identifies future directions for research and surveillance, and explores possible
      beneficial strategies. The Report Card highlighted that between 64% and 85% of
      Australians aged 5-17 years participate in organised sports, a rate higher than
      alternate forms of physical activity such as active transportation, active play
      and school based physical activity. This finding reflects Australia's position as
      one of the global leaders for participating in organised sport. Future research
      and surveillance methodologies however, need to incorporate standardised metrics
      that aim to capture more detailed data regarding organised sport participation.
      Facilitating access for all children and preventing dropout from organised sports
      are important initiatives to improve current levels of sport participation.
      However, given that 80% of Australians aged 5-17 years are not sufficiently
      physically active to achieve the daily recommendation, participation in sport
      alone is not enough to ensure that children can accrue the health benefits
      associated with being physically active. As such, there is a pressing need to
      develop strategies that engage children in other forms of physical activity such
      as active transportation and active play. 

PMID- 25979480
TI  - High-level expression of pseudolysin, the extracellular elastase of Pseudomonas
      aeruginosa, in Escherichia coli and its purification.
AB  - Pseudolysin is the extracellular elastase of Pseudomonas aeruginosa and belongs
      to the thermolysin-like family of metallopeptidases. Pseudolysin has been
      identified as a robust drug target and a biotechnologically important enzyme in
      the tanning industry. Previous attempts to purify active pseudolysin from P.
      aeruginosa or by expression in Escherichia coli yielded low quantities.
      Considerable expression and purification of secreted pseudolysin from Pichia
      pastoris has been reported but it is time-consuming and not cost-effective. We
      report the successful large-scale expression of pseudolysin in E. coli and
      purification of the correctly folded and active protein. The lasB gene that codes
      for the enzymatically active mature 33-kilodalton pseudolysin was expressed with
      a histidine tag under the control of the T7 promoter. Pseudolysin expressed
      highly in E. coli and was solubilized and purified in 8M urea by metal affinity
      chromatography. The protein was simultaneously further purified, refolded and
      buffer-exchanged on a preparative Superdex 200 column by a modified urea reverse
      gradient size exclusion chromatography. Using this technique, precipitation of
      pseudolysin was completely eliminated. Refolded pseudolysin was found to be
      active as assessed by its ability to hydrolyze N-succinyl-ala-ala-ala-p
      nitroanilide. The purification scheme yielded approximately 40 mg of pseudolysin
      per liter of expression culture and specific activity of 3.2U/mg of protein using
      N-succinyl-ala-ala-ala-p-nitroanilide as substrate. This approach provides a
      reproducible strategy for high-level expression and purification of active
      metallopeptidases and perhaps other inclusion body-forming and precipitation
      prone proteins.

PMID- 25979481
TI  - WITHDRAWN: Study coexistence albumin, fibrinogen and complement on surface blood
      vessels and placental.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25979482
TI  - Stroma, Stroma Everywhere (Far More Than You Think).
AB  - Pancreatic ductal adenocarcinomas with high stromal content are shown to have
      greatly reduced overall survival, consistent with previous reports that stroma
      may limit drug delivery. In contrast to expectations, metastatic lesions were
      found to harbor as much stroma as primary tumors.

PMID- 25979483
TI  - Subclonal Genomic Architectures of Primary and Metastatic Colorectal Cancer Based
      on Intratumoral Genetic Heterogeneity.
AB  - PURPOSE: The intratumoral heterogeneity (ITH) and the evolution of genomic
      architectures associated with the development of distant metastases are not well
      understood in colorectal cancers. EXPERIMENTAL DESIGN: We performed multiregion
      biopsies of primary and liver metastatic regions from five colorectal cancers
      with whole-exome sequencing and copy number profiling. RESULTS: In addition to a
      substantial level of genetic ITH, multiregion genetic profiling identifies the
      subclonal mutational architecture, leading to the region-based or spatial
      categorization of somatic mutations and the inference of intratumoral
      evolutionary history of cancers. The universal mutations (those observed in all
      the regional biopsies) are enriched in known cancer genes such as APC and TP53
      with distinct mutational spectra compared with biopsy- or region-specific
      mutations, suggesting that major operative mutational mechanisms and their
      selective pressures are not constant across the metastatic progression. The
      phylogenies inferred from genomic data show branching evolutionary patterns where
      some primary biopsies are often segregated with metastastic lesions. Our analyses
      also revealed that copy number changes such as the chromosomal gains of c-MYC and
      chromothripsis can be region specific and the potential source of genetic ITH.
      CONCLUSIONS: Our data show that the genetic ITH is prevalent in colorectal cancer
      serving as a potential driving force to generate metastasis-initiating clones and
      also as a means to infer the intratumoral evolutionary history of cancers. The
      paucity of recurrent metastasis-clonal events suggests that colorectal cancer
      distant metastases may not follow a uniform course of genomic evolution, which
      should be considered in the genetic diagnosis and the selection of therapeutic
      targets for the advanced colorectal cancer.

PMID- 25979484
TI  - Association of PIK3CA Mutation Status before and after Neoadjuvant Chemotherapy
      with Response to Chemotherapy in Women with Breast Cancer.
AB  - PURPOSE: The association between PIK3CA mutations and response to neoadjuvant
      chemotherapy in women with primary breast cancer is not fully elucidated.
      EXPERIMENTAL DESIGN: PIK3CA mutations in breast cancer tissues that were taken
      prior to the initiation of neoadjuvant chemotherapy were identified in 729
      operable primary breast cancer patients who received neoadjuvant chemotherapy.
      Among these, the PIK3CA mutations were also reassessed in tumor tissues procured
      following operation in 102 patients after completion of neoadjuvant chemotherapy.
      RESULTS: A total of 206 out of 729 (28.3%) patients had PIK3CA mutations, and
      19.5% of patients (142/729) in this cohort achieved a pathologic complete
      response (pCR) after neoadjuvant chemotherapy. Patients with PIK3CA mutations
      exhibited a lower pCR rate than did those with wild-type (14.6% vs. 21.4%, P =
      0.035). No significant differences in disease-free survival (DFS) or distant
      disease-free survival (DDFS) were observed between PIK3CA mutant and wild-type in
      the entire study population. Among the 102 patients with PIK3CA mutation statuses
      available before and after neoadjuvant chemotherapy, 24 patients (23.5%) had
      PIK3CA mutations before neoadjuvant chemotherapy. Of these 24 patients, 15
      patients retained their initial PIK3CA mutations and 9 patients lost their
      initial mutations after neoadjuvant chemotherapy. Patients who retained the
      initial mutations after neoadjuvant chemotherapy (n = 15) had a worse DDFS than
      the remaining patients (n = 87) in this subgroup [unadjusted HR, 2.34; 95%
      confidence interval (CI), 0.98-5.62; P = 0.050]. CONCLUSIONS: Patients with
      PIK3CA mutations are less likely to respond to neoadjuvant chemotherapy. Patients
      who retain their initial PIK3CA mutations after neoadjuvant chemotherapy have an
      unfavorable survival.

PMID- 25979487
TI  - Neuropeptide S reduces mouse aggressiveness in the resident/intruder test through
      selective activation of the neuropeptide S receptor.
AB  - Neuropeptide S (NPS) regulates various biological functions by selectively
      activating the NPS receptor (NPSR). In particular NPS evokes robust anxiolytic
      like effects in rodents together with a stimulant and arousal promoting action.
      The aim of the study was to investigate the effects of NPS on the aggressiveness
      of mice subjected to the resident/intruder test. Moreover the putative role
      played by the endogenous NPS/NPSR system in regulating mice aggressiveness was
      investigating using mice lacking the NPSR receptor (NPSR(-/-)) and the NPSR
      selective antagonists [(t)Bu-D-Gly(5)]NPS and SHA 68. NPS (0.01-1 nmol, icv)
      reduced, in a dose dependent manner, both the time that resident mice spent
      attacking the intruder mice and their number of attacks, producing
      pharmacological effects similar to those elicited by the standard anti-aggressive
      drug valproate (300 mg/kg, ip). This NPS effect was evident in NPSR wild type
      (NPSR(+/+)) mice but completely disappeared in NPSR(-/-) mice. Moreover, NPSR(-/
      ) mice displayed a significantly higher time spent attacking than NPSR(+/+) mice.
      [(t)Bu-D-Gly(5)]NPS (10 nmol, icv) did not change the behavior of mice in the
      resident/intruder test but completely counteracted NPS effects. SHA 68 (50 mg/kg,
      ip) was inactive per se and against NPS. In conclusion, this study demonstrated
      that NPS produces anti-aggressive effects in mice through the selective
      activation of NPSR and that the endogenous NPS/NPSR system can exert a role in
      the control of aggressiveness levels under the present experimental conditions. 

PMID- 25979485
TI  - Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in
      Multiple Myeloma.
AB  - PURPOSE: PD-1/PD-L1 signaling promotes tumor growth while inhibiting effector
      cell-mediated antitumor immune responses. Here, we assessed the impact of single
      and dual blockade of PD-1/PD-L1, alone or in combination with lenalidomide, on
      accessory and immune cell function as well as multiple myeloma cell growth in the
      bone marrow (BM) milieu. EXPERIMENTAL DESIGN: Surface expression of PD-1 on
      immune effector cells, and PD-L1 expression on CD138(+) multiple myeloma cells
      and myeloid-derived suppressor cells (MDSC) were determined in BM from newly
      diagnosed (ND) multiple myeloma and relapsed/refractory (RR) multiple myeloma
      versus healthy donor (HD). We defined the impact of single and dual blockade of
      PD-1/PD-L1, alone and with lenalidomide, on autologous anti-multiple myeloma
      immune response and tumor cell growth. RESULTS: Both ND and RR patient multiple
      myeloma cells have increased PD-L1 mRNA and surface expression compared with HD.
      There is also a significant increase in PD-1 expression on effector cells in
      multiple myeloma. Importantly, PD-1/PD-L1 blockade abrogates BM stromal cell
      (BMSC)-induced multiple myeloma growth, and combined blockade of PD-1/PD-L1 with
      lenalidomide further inhibits BMSC-induced tumor growth. These effects are
      associated with induction of intracellular expression of IFNgamma and granzyme B
      in effector cells. Importantly, PD-L1 expression in multiple myeloma is higher on
      MDSC than on antigen-presenting cells, and PD-1/PD-L1 blockade inhibits MDSC
      mediated multiple myeloma growth. Finally, lenalidomide with PD-1/PD-L1 blockade
      inhibits MDSC-mediated immune suppression. CONCLUSIONS: Our data therefore
      demonstrate that checkpoint signaling plays an important role in providing the
      tumor-promoting, immune-suppressive microenvironment in multiple myeloma, and
      that PD-1/PD-L1 blockade induces anti-multiple myeloma immune response that can
      be enhanced by lenalidomide, providing the framework for clinical evaluation of
      combination therapy.

PMID- 25979486
TI  - An animal model of female adolescent cannabinoid exposure elicits a long-lasting
      deficit in presynaptic long-term plasticity.
AB  - Cannabis continues to be the most accessible and popular illicit recreational
      drug. Whereas current data link adolescence cannabinoid exposure to increased
      risk for dependence on other drugs, depression, anxiety disorders and psychosis,
      the mechanism(s) underlying these adverse effects remains controversial. Here we
      show in a mouse model of female adolescent cannabinoid exposure deficient
      endocannabinoid (eCB)-mediated signaling and presynaptic forms of long-term
      depression at adult central glutamatergic synapses in the prefrontal cortex.
      Increasing endocannabinoid levels by blockade of monoacylglycerol lipase, the
      primary enzyme responsible for degrading the endocannabinoid 2
      arachidonoylglycerol (2-AG), with the specific inhibitor JZL 184 ameliorates eCB
      LTD deficits. The observed deficit in cortical presynaptic signaling may
      represent a neural maladaptation underlying network instability and abnormal
      cognitive functioning. Our study suggests that adolescent cannabinoid exposure
      may permanently impair brain functions, including the brain's intrinsic ability
      to appropriately adapt to external influences. 

PMID- 25979488
TI  - Probing the pharmacology of G protein-coupled receptors with fluorescent ligands.
AB  - G protein-coupled receptors control a wide range of physiological processes and
      are the target for many clinically used drugs. Understanding the way in which
      receptors bind agonists and antagonists, their organisation in the membrane and
      their regulation after agonist binding are important properties which are key to
      developing new drugs. One way to achieve this knowledge is through the use of
      fluorescent ligands, which have been used to study the expression and function of
      receptors in endogenously expressing systems. Fluorescent ligands with
      appropriate imaging properties can be used in conjunction with confocal
      microscopy to investigate the regulation of receptors after activation.
      Alternatively, through the use of single molecule microscopy, they can probe the
      spatial organisation of receptors within the membrane. This review focuses on the
      techniques in which fluorescent ligands have been used and the novel aspects of G
      protein-coupled receptor pharmacology which have been uncovered. This article is
      part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. 

PMID- 25979490
TI  - Dairy foods and dairy proteins in the management of type 2 diabetes: a systematic
      review of the clinical evidence.
AB  - Type 2 diabetes mellitus (T2DM) is a growing public health concern affecting
      hundreds of millions of people worldwide and costing the global economy hundreds
      of billions of dollars annually. This chronic disease damages the blood vessels
      and increases the risk of other cardiometabolic ailments such as cardiovascular
      disease and stroke. If left unmanaged it can also lead to nerve damage, kidney
      damage, blindness, and amputation. For the most part, many of these symptoms can
      be prevented or reduced through simple dietary modifications and proper
      nutrition. Therefore, identifying relatively inexpensive and easily implementable
      dietary modifications for the prevention and management of T2DM is of
      considerable value to human health and healthcare modalities around the globe.
      Protein-rich dairy products have consistently been shown in epidemiologic studies
      to be beneficial for reducing the risk of developing T2DM. The clinical evidence
      regarding both dairy foods and dairy proteins (i.e., casein and whey protein)
      have shown promise for improving insulin secretion in individuals with T2DM.
      However, the clinical research on dairy protein supplementation in subjects with
      T2DM has been limited to acute studies. These studies have been mostly
      descriptive and have not been focused on important T2DM endpoints such as
      prevention, management, or treatment. Long-term studies are clearly needed to
      help researchers and medical professionals better understand the effects of
      consistent dairy protein intake on the metabolic health of humans with T2DM. 

PMID- 25979491
TI  - Controversies surrounding high-protein diet intake: satiating effect and kidney
      and bone health.
AB  - Long-term consumption of a high-protein diet could be linked with metabolic and
      clinical problems, such as loss of bone mass and renal dysfunction. However,
      although it is well accepted that a high-protein diet may be detrimental to
      individuals with existing kidney dysfunction, there is little evidence that high
      protein intake is dangerous for healthy individuals. High-protein meals and foods
      are thought to have a greater satiating effect than high-carbohydrate or high-fat
      meals. The effect of high-protein diets on the modulation of satiety involves
      multiple metabolic pathways. Protein intake induces complex signals, with peptide
      hormones being released from the gastrointestinal tract and blood amino acids and
      derived metabolites being released in the blood. Protein intake also stimulates
      metabolic hormones that communicate information about energy status to the brain.
      Long-term ingestion of high amounts of protein seems to decrease food intake,
      body weight, and body adiposity in many well-documented studies. The aim of this
      article is to provide an extensive overview of the efficacy of high protein
      consumption in weight loss and maintenance, as well as the potential consequences
      in human health of long-term intake. 

PMID- 25979493
TI  - MUFAs.

PMID- 25979492
TI  - Immune cell-mediated protection of the mammary gland and the infant during
      breastfeeding.
AB  - Breastfeeding has been regarded first and foremost as a means of nutrition for
      infants, providing essential components for their unique growth and developmental
      requirements. However, breast milk is also rich in immunologic factors,
      highlighting its importance as a mediator of protection. In accordance with its
      evolutionary origin, the mammary gland offers via the breastfeeding route
      continuation of the maternal to infant immunologic support established in utero.
      At birth, the infant's immune system is immature, and although it was exposed to
      the maternal microbial flora during pregnancy, it experiences an abrupt change in
      its microbial environment during and after birth, which is challenging and
      renders the infant highly susceptible to infection. Active and passive immunity
      protects the infant via breast milk, which is rich in immunoglobulins,
      lactoferrin, lysozyme, cytokines, and numerous other immunologic factors,
      including maternal leukocytes. Breast milk leukocytes provide active immunity and
      promote development of immunocompetence in the infant. Additionally, it has been
      speculated that they play a role in the protection of the mammary gland from
      infection. Leukocytes are thought to exert these functions via phagocytosis,
      secretion of antimicrobial factors and/or antigen presentation in both the
      mammary gland and the gastrointestinal tract of the infant, and also in other
      infant tissues, where they are transported via the systemic circulation.
      Recently, it has been demonstrated that breast milk leukocytes respond
      dynamically to maternal as well as infant infections, and are fewer in
      nonexclusively compared with exclusively breastfeeding dyads, further emphasizing
      their importance for both the mother and infant. This review summarizes the
      current knowledge of human milk leukocytes and factors influencing them, and
      presents recent novel findings supporting their potential as a diagnostic marker
      for infections of the lactating breast and of the breastfed infant. 

PMID- 25979494
TI  - International Food Policy Research Institute. 2014. Washington, DC: Global
      Nutrition Report 2014: actions and accountability to accelerate the world's
      progress on nutrition.

PMID- 25979489
TI  - Comorbidities in Neurology: Is adenosine the common link?
AB  - Comorbidities in Neurology represent a major conceptual and therapeutic
      challenge. For example, temporal lobe epilepsy (TLE) is a syndrome comprised of
      epileptic seizures and comorbid symptoms including memory and psychiatric
      impairment, depression, and sleep dysfunction. Similarly, Alzheimer's disease
      (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are
      accompanied by various degrees of memory dysfunction. Patients with AD have an
      increased likelihood for seizures, whereas all four conditions share certain
      aspects of psychosis, depression, and sleep dysfunction. This remarkable overlap
      suggests common pathophysiological mechanisms, which include synaptic dysfunction
      and synaptotoxicity, as well as glial activation and astrogliosis. Astrogliosis
      is linked to synapse function via the tripartite synapse, but astrocytes also
      control the availability of gliotransmitters and adenosine. Here we will
      specifically focus on the 'adenosine hypothesis of comorbidities' implying that
      astrocyte activation, via overexpression of adenosine kinase (ADK), induces a
      deficiency in the homeostatic tone of adenosine. We present evidence from patient
      derived samples showing astrogliosis and overexpression of ADK as common
      pathological hallmark of epilepsy, AD, PD, and ALS. We discuss a transgenic
      'comorbidity model', in which brain-wide overexpression of ADK and resulting
      adenosine deficiency produces a comorbid spectrum of seizures, altered
      dopaminergic function, attentional impairment, and deficits in cognitive domains
      and sleep regulation. We conclude that dysfunction of adenosine signaling is
      common in neurological conditions, that adenosine dysfunction can explain co
      morbid phenotypes, and that therapeutic adenosine augmentation might be effective
      for the treatment of comorbid symptoms in multiple neurological conditions. 

PMID- 25979495
TI  - Is dietary sodium policy actually based on science?

PMID- 25979496
TI  - Reply to SN Thornton.

PMID- 25979497
TI  - Sustainable diet studies show co-benefits for greenhouse gas emissions and public
      health.

PMID- 25979498
TI  - Reply to L Aleksandrowicz et al.

PMID- 25979499
TI  - Erratum for Graudal et al. The significance of duration and amount of sodium
      reduction intervention in normotensive and hypertensive individuals: a meta
      analysis. Adv Nutr 2015;6:169-77.

PMID- 25979501
TI  - Executive summary.
AB  - The impact of dietary fats and oils on health continues to be a controversial
      subject. In addition, the ability of the food industry to freely alter the fat
      content and composition of foods to meet dietary recommendations is limited by
      how these food components affect food quality and stability. Therefore, a recent
      workshop was held to bring together food and nutrition scientists to highlight
      nutritional research and product innovations that explore the nutritional impact
      of fatty acids in the food supply. The latest research on metabolic responses and
      health benefits associated with foods made with new nutritional and functional
      oils was discussed, along with a detailed look at how science-based advances in
      preparation methods and processing technologies affect the nutrient profile of
      food products, including potato products. Additional discussion was provided on
      how oil innovations align with dietary guidance and policy. This supplement issue
      presents articles on those presentations. 

PMID- 25979502
TI  - The science of fatty acids and inflammation.
AB  - Inflammation is believed to play a central role in many of the chronic diseases
      that characterize modern society. In the past decade, our understanding of how
      dietary fats affect our immune system and subsequently our inflammatory status
      has grown considerably. There are compelling data showing that high-fat meals
      promote endotoxin [e.g., lipopolysaccharide (LPS)] translocation into the
      bloodstream, stimulating innate immune cells and leading to a transient
      postprandial inflammatory response. The nature of this effect is influenced by
      the amount and type of fat consumed. The role of various dietary constituents,
      including fats, on gut microflora and subsequent health outcomes in the host is
      another exciting and novel area of inquiry. The impact of specific fatty acids on
      inflammation may be central to how dietary fats affect health. Three key fatty
      acid-inflammation interactions are briefly described. First, the evidence
      suggests that saturated fatty acids induce inflammation in part by mimicking the
      actions of LPS. Second, the often-repeated claim that dietary linoleic acid
      promotes inflammation was not supported in a recent systematic review of the
      evidence. Third, an explanation is offered for why omega-3 (n-3) polyunsaturated
      fatty acids are so much less anti-inflammatory in humans than in mice. The
      article closes with a cautionary tale from the genomic literature that
      illustrates why extrapolating the results from inflammation studies in mice to
      humans is problematic. 

PMID- 25979503
TI  - Effect of macronutrient composition on short-term food intake and weight loss.
AB  - The purpose of this review is to describe the role of macronutrient composition
      on the suppression of short-term food intake (FI) and weight loss. The effects of
      macronutrient composition on short-term FI will be reviewed first, followed by a
      brief examination of longer-term clinical trials that vary in effects of dietary
      macronutrient composition on weight loss. The objectives were: 1) to examine the
      effect of macronutrient composition on the suppression of short-term FI, 2) to
      determine whether some macronutrient sources suppress FI beyond their provision
      of energy, 3) to assess the combined effects of macronutrients on FI and glycemic
      response, and 4) to determine whether knowledge of the effect of macronutrients
      on short-term FI has led to greater success in spontaneous weight loss, adherence
      to energy-restricted diets, and better weight maintenance after weight loss.
      Although knowledge of macronutrient composition on short-term FI regulation has
      advanced our understanding of the role of diet composition on energy balance, it
      has yet to lead to greater success in long-term weight loss and weight
      maintenance. It is clear from this review that many approaches based on
      manipulating dietary macronutrient composition can help people lose weight as
      long as they follow the diets. However, only by evaluating the interaction
      between the physiologic systems that govern FI and body weight may the benefits
      of dietary macronutrient composition be fully realized. 

PMID- 25979504
TI  - Challenges of utilizing healthy fats in foods.
AB  - Over the past few decades, the Dietary Guidelines for Americans has consistently
      recommended that consumers decrease consumption of saturated fatty acids due to
      the correlation of saturated fatty acid intake with coronary artery disease. This
      recommendation has not been easy to achieve because saturated fatty acids play an
      important role in the quality, shelf life, and acceptability of foods. This is
      because solid fats are critical to producing desirable textures (e.g.,
      creaminess, lubrication, and melt-away properties) and are important in the
      structure of foods such as frozen desserts, baked goods, and confectionary
      products. In addition, replacement of saturated fats with unsaturated fats is
      limited by their susceptibility to oxidative rancidity, which decreases product
      shelf life, causes destruction of vitamins, and forms potentially toxic
      compounds. This article will discuss the fundamental chemical and physical
      properties in fats and how these properties affect food texture, structure,
      flavor, and susceptibility to degradation. The current sources of solid fats will
      be reviewed and potential replacements for solid fats will be discussed. 

PMID- 25979505
TI  - The carbohydrate-fat problem: can we construct a healthy diet based on dietary
      guidelines?
AB  - The inclusion of nutrition economics in dietary guidance would help ensure that
      the Dietary Guidelines for Americans benefit equally all segments of the US
      population. The present review outlines some novel metrics of food affordability
      that assess nutrient density of foods and beverages in relation to cost.
      Socioeconomic disparities in diet quality in the United States are readily
      apparent. In general, groups of lower socioeconomic status consume cheaper, lower
      quality diets and suffer from higher rates of noncommunicable diseases. Nutrient
      profiling models, initially developed to assess the nutrient density of foods,
      can be turned into econometric models that assess both calories and nutrients per
      reference amount and per unit cost. These novel metrics have been used to
      identify individual foods that were affordable, palatable, culturally acceptable,
      and nutrient rich. Not all nutrient-rich foods were expensive. In dietary
      surveys, both local and national, some high-quality diets were associated with
      relatively low cost. Those population subgroups that successfully adopted dietary
      guidelines at an unexpectedly low monetary cost were identified as "positive
      deviants." Constructing a healthy diet based on dietary guidelines can be done,
      provided that nutrient density of foods, their affordability, as well as taste
      and social norms are all taken into account. 

PMID- 25979506
TI  - Emerging nutrition science on fatty acids and cardiovascular disease:
      nutritionists' perspectives.
AB  - Recent dietary guidance for heart health recommends a reduction (by ~50%) in
      saturated fatty acid (SFA) intake to reduce LDL cholesterol and to decrease risk
      of cardiovascular disease (CVD). The 2010 Dietary Guidelines for Americans
      recommends substituting unsaturated fat [both polyunsaturated and monounsaturated
      fatty acids (PUFAs and MUFAs, respectively)] for SFAs. There are many dietary
      options that can be implemented to replace SFAs, given the different sources of
      unsaturated fats in the food supply. Compelling evidence exists for the
      cardioprotective benefits of n-3 (omega-3) PUFAs, both marine- and plant-derived.
      In addition, the evidence of cardioprotective benefits of n-6 (omega-6) PUFAs is
      strong, whereas that for MUFAs is mixed, although there is emerging evidence of
      benefits. Quantitatively, lowering SFAs by 50% will require, in part,
      substituting food sources of n-6 and n-3 PUFAs and MUFAs for food sources of
      SFAs. The use of n-3 PUFAs as a replacement for SFAs will result in a shortfall
      in reaching the SFA goal because of the relatively low amounts that can be
      incorporated in the diet, even with very high n-3 PUFA substitution. SFAs also
      can be replaced with dietary carbohydrate and/or protein. Replacing SFAs with
      carbohydrate, specifically refined sources, however, has little impact on
      reducing CVD risk. There is evidence about the health benefits of dietary protein
      on CVD risk, which merits study. Dietary guidelines have advanced considerably
      with the "replacement of SFA with unsaturated fat message" instead of
      recommending decreasing SFAs alone. A key question that remains is what is the
      optimal mix of macronutrients to maximally reduce CVD risk. 

PMID- 25979509
TI  - Science-based regulatory and policy considerations in nutrition.
AB  - Scientific evidence is necessary for the development of effective and enforceable
      regulations and government policy. To use scientific information appropriately, a
      systematic approach is needed for review and evaluation of the evidence. Federal
      agencies in the United States have developed useful approaches for such a review
      and evaluation to develop nutrition labeling, including health claims, and for
      updating of the Dietary Guidelines for Americans. The WHO is using a systematic
      evaluation process to update its recommendations on diet and health. The results
      of such reviews also highlight research needs to address relevant gaps in our
      knowledge. 

PMID- 25979508
TI  - Recent advances in fatty acid perception and genetics.
AB  - This article summarizes new knowledge about the contribution of genetic variation
      to person-to-person differences underlying some sensory aspects of dietary fatty
      acids. Receptors on the taste cells of the human tongue arise from genes that
      have marked variation in DNA sequence, which, in some cases, is associated with
      differences in how these lipids in foods are perceived. These perceptual
      differences may affect food selection. 

PMID- 25979507
TI  - Reduced-fat foods: the complex science of developing diet-based strategies for
      tackling overweight and obesity.
AB  - Fat plays multiple roles in determining the desirable physicochemical properties,
      sensory attributes, nutritional profile, and biologic response of food products.
      Overconsumption of fats is linked to chronic diseases, such as obesity, coronary
      heart disease, diabetes, and cancer. There is therefore a need to develop reduced
      fat products with physicochemical properties and sensory profiles that match
      those of their full-fat counterparts. In addition, foods may be redesigned to
      increase the feelings of satiety and satiation, and thereby reduce overall food
      intake. The successful design of these types of functional foods requires a good
      understanding of the numerous roles that fat plays in determining food attributes
      and the development of effective strategies to replace these attributes. This
      article provides an overview of the current understanding of the influence of fat
      on the physicochemical and physiologic attributes of emulsion-based food products
      and highlights approaches to create high-quality foods with reduced-fat contents.

PMID- 25979510
TI  - Development of the SoFAS (solid fats and added sugars) concept: the 2010 Dietary
      Guidelines for Americans.
AB  - The diets of most US children and adults are poor, as reflected by low diet
      quality scores, when compared with the recommendations of the Dietary Guidelines
      for Americans (DGAs). Contributing to these low scores is that most Americans
      overconsume solid fats, which may contain saturated fatty acids and added sugars;
      although alcohol consumption was generally modest, it provided few nutrients.
      Thus, the 2005 DGAs generated a new recommendation: to reduce intakes of solid
      fats, alcohol, and added sugars (SoFAAS). What precipitated the emergence of the
      new SoFAAS terminology was the concept of discretionary calories (a "calorie" is
      defined as the amount of energy needed to increase the temperature of 1 kg of
      water by 1 degrees C), which were defined as calories consumed after an
      individual had met his or her recommended nutrient intakes while consuming fewer
      calories than the daily recommendation. A limitation with this concept was that
      additional amounts of nutrient-dense foods consumed beyond the recommended amount
      were also considered discretionary calories. The rationale for this was that if
      nutrient-dense foods were consumed beyond recommended amounts, after total energy
      intake was met then this constituted excess energy intake. In the 2010 DGAs, the
      terminology was changed to solid fats and added sugars (SoFAS); thus, alcohol was
      excluded because it made a minor contribution to overall intake and did not apply
      to children. The SoFAS terminology also negated nutrient-dense foods that were
      consumed in amounts above the recommendations for the specific food groups in the
      food patterns. The ambiguous SoFAS terminology was later changed to "empty
      calories" to reflect only those calories from solid fats and added sugars (and
      alcohol if consumed beyond moderate amounts). The purpose of this review is to
      provide an historical perspective on how the dietary recommendations went from
      SoFAAS to SoFAS and how discretionary calories went to empty calories between the
      2005 and 2010 DGAs. This information will provide practitioners, as well as the
      public, with valuable information to better understand the evolution of SoFAS
      over time. 

PMID- 25979511
TI  - Changes in mean intake of fatty acids and intake of saturated and trans fats from
      potatoes: NHANES 2005-2006, 2007-2008, and 2009-2010.
AB  - Studies have shown that higher than usual intakes of trans fatty acids (TFAs)
      have adverse effects on blood lipids. Because of this, in 2006 the US FDA
      mandated labeling of TFAs on food packages. The food and restaurant industries,
      including the potato industry, reformulated their foods to reduce or eliminate
      partially hydrogenated vegetable oils and TFAs. Before mandatory labeling, grain
      based desserts, yeast breads, and French-fried potatoes (FFPs) were the top
      sources of TFAs in the food supply; by 2007, potato food manufacturers and quick
      service restaurants had reduced or eliminated TFAs without increasing saturated
      fatty acids (SFAs). FFPs are no longer a source of TFAs in the food supply. This
      study examined energy and fatty acid intake among children aged 6-11 y,
      adolescents aged 12-18 y, and adults aged >=19 y across 3 time periods by using
      data from the NHANES 2005-2006, 2007-2008, and 2009-2010. On average, intakes of
      total energy, total fat, SFAs, and monounsaturated fatty acids (MUFAs) decreased
      significantly between 2005-2006 and 2009-2010 among children and adolescents;
      however, the intake of polyunsaturated fatty acids (PUFAs) did not change. Among
      adults, intakes of total fat, SFAs, and MUFAs decreased; however, total energy
      and PUFA intake did not change. On the day of the 2009-2010 survey, ~13% of
      children and 10% of adolescents reported consuming fried FFPs, whereas <7% of
      adults reported consumption of fried FFPs. Intakes of SFAs and TFAs from fried
      FFPs decreased significantly between 2005-2006 and 2009-2010 among children,
      adolescents, and adults. This study confirms that intake of TFAs from FFPs is
      trivial. 

PMID- 25979512
TI  - Extracellular melanogenesis inhibitory activity and the structure-activity
      relationships of ugonins from Helminthostachys zeylanica roots.
AB  - Ugonin J, K, and L, which are luteolin derivatives, were isolated from
      Helminthostachys zeylanica roots by a series of chromatographic separations of a
      50% ethanol/water extract. They were identified using nuclear magnetic resonance
      (NMR), ultraviolet (UV) spectra, and ultra-performance liquid chromatography
      coupled to time-of-flight mass spectrometry (UPLC-TOF-MS). In this study, the
      intra and extracellular melanogenic activity of the ugonins were determined using
      B16 melanoma cells. The results showed that ugonin J at 12.5, 25, and 50MUM
      reduced extracellular melanin contents to 75, 16, and 14%, respectively, compared
      to the control. This indicates that ugonin J showed a stronger activity than
      arbutin, used as the positive control. Moreover, ugonin K showed a more potent
      inhibition with 19, 8, and 9% extracellular melanin reduction at the same
      concentrations, than that shown by ugonin J. In contrast, ugonin L did not
      inhibit intra- or extracellular melanogenic activity. Furthermore, in order to
      investigate the structure-activity relationships of the ugonins, the intra- and
      extracellular melanogenic activity of luteolin, methylluteolin, quercetin,
      eriodictyol, apigenin, and chrysin were determined. Consequently, it was
      suggested that the catechol and flavone skeleton of ugonin K is essential for the
      extracellular melanogenic inhibitory activity, and the low polarity substituent
      groups on the A ring of ugonin K may increase the activity. 

PMID- 25979513
TI  - The surgery spring.

PMID- 25979514
TI  - Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations
      and emerging concepts.
AB  - Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited
      diseases. They include three overlapping phenotypes: familial cold
      autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile
      neurological cutaneous articular syndrome/neonatal onset multisystem
      autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and
      urticarial skin rash are the main clinical features of these conditions. Renal
      amyloidosis and sensorineural complications may occur. Gain-of-function mutations
      in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a
      multimolecular complex involved in the inflammatory process. Missense mutations
      are almost always encountered, particularly in exon 3, which encodes the
      nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next
      generation sequencing will grant access to new insights about NLRP3 implication
      in oligogenic and multifactorial diseases. 

PMID- 25979515
TI  - An unrecognised case of metabolic acidosis following neobladder augmentation
      cystoplasty.
AB  - INTRODUCTION: We present a case where there was a delay in the diagnosis of
      severe metabolic acidosis in a patient with an orthotopic neobladder. There are a
      growing number of patients with orthotopic neobladders and a wider range of
      clinicians are encountering these patients. A delay in the diagnosis can lead to
      significant morbidity but if identified early it can be easily treated.
      PRESENTATION OF CASE: A 59-year old patient with a recent neobladder augmentation
      cystoplasty was admitted under the medical team with a metabolic acidosis which
      was incorrectly presumed to be secondary to urosepsis. His condition rapidly
      deteriorated until a surgical review identified hyperchloremic metabolic acidosis
      secondary to neobladder augmentation. The patient required admission to the
      intensive care unit where he was treated with intravenous alkalising therapy
      which produced rapid metabolic improvement. Following a full recovery, he
      underwent neo-bladder excision and ileal conduit formation. DISCUSSION:
      Hyperchloraemic metabolic acidosis develops due to the bowel segment absorbing
      urinary constituents including ammonium, hydrogen ions and chloride in exchange
      for sodium and bicarbonate. It can be diagnosed by careful interpretation of the
      arterial blood gas and calculation of the anion gap. This hyperchloraemic
      metabolic acidosis can be corrected with alkalizing agents combined with
      catheterisation. CONCLUSION: Hyperchloremic metabolic acidosis is a well
      established complication of urinary diversion. Patient with orthotopic neobladder
      with high residual urine and large capacity are at even higher risk of metabolic
      acidosis. This information should be clearly documented in the post-operative
      discharge documentation to ensure early recognition by non-specialists.

PMID- 25979516
TI  - Environmental factors, including cannabis, are strongly related to the age of
      onset and morbidity of schizophrenia.

PMID- 25979517
TI  - (Q)SAR: A Tool for the Toxicologist.
AB  - A continuing education (CE) course at the 2014 American College of Toxicology
      annual meeting covered the topic of (Quantitative) Structure-Activity
      Relationships [(Q)SAR]. The (Q)SAR methodologies use predictive computer modeling
      based on predefined rules to describe the relationship between chemical structure
      and a chemical's associated biological activity or statistical tools to find
      correlations between biologic activity and the molecular structure or properties
      of a compound. The (Q)SAR has applications in risk assessment, drug discovery,
      and regulatory decision making. Pressure within industry to reduce the cost of
      drug development and societal pressure for government regulatory agencies to
      produce more accurate and timely risk assessment of drugs and chemicals have
      necessitated the use of (Q)SAR. Producing a high-quality (Q)SAR model depends on
      many factors including the choice of statistical methods and descriptors, but
      first and foremost the quality of the data input into the model. Understanding
      how a (Q)SAR model is developed and applied is critical to the successful use of
      such a tool. The CE session covered the basic principles of (Q)SAR, practical
      applications of these computational models in toxicology, how regulatory agencies
      use and interpret (Q)SAR models, and potential pitfalls of using them. 

PMID- 25979518
TI  - Affected functional networks associated with sentence production in classic
      galactosemia.
AB  - Patients with the inherited metabolic disorder classic galactosemia have language
      production impairments in several planning stages. Here, we assessed potential
      deviations in recruitment and connectivity across brain areas responsible for
      language production that may explain these deficits. We used functional magnetic
      resonance imaging (fMRI) to study neural activity and connectivity while
      participants carried out a language production task. This study included 13
      adolescent patients and 13 age- and gender-matched healthy controls. Participants
      passively watched or actively described an animated visual scene using two
      conditions, varying in syntactic complexity (single words versus a sentence).
      Results showed that patients recruited additional and more extensive brain
      regions during sentence production. Both groups showed modulations with syntactic
      complexity in left inferior frontal gyrus (IFG), a region associated with
      syntactic planning, and in right insula. In addition, patients showed a
      modulation with syntax in left superior temporal gyrus (STG), whereas the
      controls did not. Further, patients showed increased activity in right STG and
      right supplementary motor area (SMA). The functional connectivity data showed
      similar patterns, with more extensive connectivity with frontal and motor
      regions, and restricted and weaker connectivity with superior temporal regions.
      Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and
      trends towards higher CBF in bilateral STG, SMA and the insula. Taken together,
      the data demonstrate that language abnormalities in classic galactosemia are
      associated with specific changes within the language network. These changes point
      towards impairments related to both syntactic planning and speech motor planning
      in these patients. 

PMID- 25979519
TI  - Significance of extravascular reservoirs of latent infection for HIV persistence
      during antiretroviral therapy.

PMID- 25979520
TI  - Association between parental age and asthma in a population-based register study.

PMID- 25979521
TI  - Genome-wide interaction study of gene-by-occupational exposure and effects on
      FEV1 levels.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex disease
      characterized by impaired lung function and airway obstruction resulting from
      interactions between multiple genes and multiple environmental exposures. Thus
      far, genome-wide association studies have largely disregarded environmental
      factors that might trigger the development of lung function impairment and COPD,
      such as occupational exposures, which are thought to contribute to 15% to 20% of
      the COPD prevalence. OBJECTIVES: We performed a genome-wide interaction study to
      identify novel susceptibility loci for occupational exposure to biological dust,
      mineral dust, and gases and fumes in relation to FEV1 levels. METHODS: We
      performed an identification analysis in 12,400 subjects from the LifeLines cohort
      study and verified our findings in 1436 subjects from a second independent
      cohort, the Vlagtwedde-Vlaardingen cohort. Additionally, we assessed whether
      replicated single nucleotide polymorphisms (SNPs) were cis-acting expression
      (mRNA) quantitative trait loci in lung tissue. RESULTS: Of the 7 replicated SNPs
      that interacted with one of the occupational exposures, several identified loci
      were plausible candidates that might be involved in biological pathways leading
      to lung function impairment, such as PCDH9 and GALNT13. Two of the 7 replicated
      SNPs were cis-acting expression quantitative trait loci associated with gene
      expression of PDE4D and TMEM176A in lung tissue. CONCLUSION: This genome-wide
      interaction study on occupational exposures in relation to the level of lung
      function identified several novel genes. Further research should determine
      whether the identified genes are true susceptibility loci for occupational
      exposures and whether these SNP-by-exposure interactions consequently contribute
      to the development of COPD.

PMID- 25979522
TI  - ORMDL deregulation increases stress responses and modulates repair pathways in
      Drosophila airways.

PMID- 25979523
TI  - Reply: To PMID 25117799.

PMID- 25979525
TI  - Locally run cholera intervention can reduce disease burden, finds study.

PMID- 25979524
TI  - Cord blood vitamin D concentrations are unrelated to atopy and wheeze in 2
      diverse birth cohort studies.

PMID- 25979526
TI  - Programmatic treatment outcomes in HIV-infected and uninfected drug-resistant TB
      patients in Khayelitsha, South Africa.
AB  - BACKGROUND: South Africa has high burdens of HIV, TB and drug-resistant TB (DR
      TB, rifampicin-resistance). Treatment outcome data for HIV-infected versus
      uninfected patients is limited. We assessed the impact of HIV and other factors
      on DR-TB treatment success, time to culture conversion, loss-from-treatment and
      overall mortality after second-line treatment initiation. METHODS: A
      retrospective cohort analysis was conducted for patients initiated on DR-TB
      treatment from 2008 to 2012, within a community-based, decentralised programme in
      Khayelitsha, South Africa. RESULTS: Among 853 confirmed DR-TB patients initiating
      second-line treatment, 605 (70.9%) were HIV infected. HIV status did not impact
      on time to sputum culture conversion nor did it impact treatment success; 48.1%
      (259/539) and 45.9% (100/218), respectively (p=0.59). In a multivariate model,
      HIV was not associated with treatment success. Death during treatment was higher
      among HIV-infected patients, but overall mortality was not significantly higher.
      HIV-infected patients with CD4 <=100 cells/ml were significantly more likely to
      die after starting treatment. CONCLUSIONS: Response to DR-TB treatment did not
      differ with HIV infection in a programmatic setting with access to antiretroviral
      treatment (ART). Earlier ART initiation at a primary care level could reduce
      mortality among HIV-infected patients presenting with low CD4 counts.

PMID- 25979527
TI  - Absence of multidrug resistance in Salmonella enterica serotypes Typhi and
      Paratyphi A isolates with intermediate susceptibility to ciprofloxacin.
AB  - BACKGROUND: We describe the antimicrobial susceptibility pattern of 64 blood
      stream isolates of Salmonella enterica serotypes Typhi and Paratyphi A studied
      from January 2013 to December 2014 at a tertiary care centre in North India.
      METHODS: Isolates were identified by standard biochemical reactions and confirmed
      by slide agglutination using specific antisera. Antimicrobial susceptibility
      testing was performed by Kirby-Bauer disc diffusion method and by E-test.
      RESULTS: In this study, 92% (46/50) of Salmonella Typhi and all Paratyphi A
      (n=14) isolates were susceptible to ampicillin, chloramphenicol and
      cotrimoxazole. Eighty percent of Typhi (40/50) and 64% (9/14) of Paratyphi A were
      intermediately susceptible to ciprofloxacin. Nineteen percent (12/64) of isolates
      were resistant to ciprofloxacin. No resistance to ceftriaxone and azithromycin
      was detected. CONCLUSIONS: Our study adds to the current knowledge of world-wide
      reports of multidrug resistance in S. Typhi.

PMID- 25979528
TI  - Changes in Left Ventricular Torsion Early Postoperatively After Aortic Valve
      Replacement and at Long-Term Follow-up.
AB  - OBJECTIVE: In patients with aortic stenosis, left ventricular systolic torsion
      (pT) is increased to overcome excessive afterload. This study assessed left
      ventricular torsion before and immediately after surgical valve replacement and
      tested the instant effect of fluid loading. DESIGN: Prospective, clinical single
      center study. SETTING: Intensive care unit of a university hospital.
      PARTICIPANTS: 12 patients undergoing elective aortic valve replacement for aortic
      stenosis. INTERVENTIONS: Echocardiography was performed on the day before
      surgery, within 18 hours after surgery including a fluid challenge, and after 2.5
      years. MEASUREMENTS AND MAIN RESULTS: pT decreased early postoperatively by 21.2%
      (23.4 degrees  +/- 5.6 degrees  to 18.4 degrees  +/- 6.9 degrees ; p = 0.012) and
      reached preoperative values at 2.5 years follow-up (24 +/- 7). Peak diastolic
      untwisting velocity occurred later early postoperatively (13% +/- 8% to 21% +/-
      9.4%; p = 0.019) and returned toward preoperative values at follow-up (10.2 +/-
      4.7 degrees ). The fluid challenge increased central venous pressure (8 +/- 4
      mmHg to 11 +/- 4 mmHg; p = 0.003) and reduced peak systolic torsion velocity
      (138.7 +/- 37.6/s to 121.3 +/- 32/s; p = 0.032). pT decreased in 3 and increased
      in 8 patients after fluid loading. Patients whose pT increased had higher early
      mitral inflow velocity postoperatively (p = 0.04) than those with decreasing pT.
      Patients with reduced pT after fluid loading received more fluids (p = 0.04) and
      had a higher positive fluid balance during the intensive care unit stay (p =
      0.03). Torsion after fluid loading correlated with total fluid input (p = 0.001)
      and cumulative fluid balance (p = 0.002). CONCLUSIONS: pT decreased early after
      aortic valve replacement but remained elevated despite elimination of aortic
      stenosis. After 2.5 years, torsion had returned to preoperative levels.

PMID- 25979529
TI  - Intraoperative Transesophageal Echocardiography: A Critical Appraisal of Its
      Current Role in the Assessment of Diastolic Dysfunction.

PMID- 25979530
TI  - Proceedings of the 2014 Annual Meeting of the Fetal Alcohol Spectrum Disorders
      Study Group.
AB  - The 2014 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting focused on
      the dual themes of the risks associated with low to moderate alcohol exposure
      during pregnancy and knowledge translation practices to enhance the impact of
      scientific research. The meeting theme was titled "Low drinking versus no
      drinking: Matching science with policy and public perception." Despite decades of
      basic science and clinical evidence that has documented the risks associated with
      prenatal alcohol exposure, there still exists confusion and uncertainty on the
      part of health professionals and the public regarding the question of whether or
      not there is a "safe" level of alcohol consumption during pregnancy. The first
      keynote presentation reviewed the data obtained from large-scale epidemiological
      studies that have attempted to address the question of relative risk associated
      with low to moderate alcohol exposure during pregnancy. This presentation was
      followed by an expert panel discussion of the state of scientific evidence
      obtained from clinical and basic science investigations concerning this question,
      and strategies for moving research evidence into policy and practice. The second
      keynote presentation presented a framework for knowledge translation and
      mobilization to move research discoveries toward implementation. The conference
      also featured updates by government agencies, FASt data talks that highlighted
      new and innovative findings in FASD research, and award presentations, including
      a lifetime achievement award presented to Dr. Kenneth Warren to acknowledge his
      longstanding support for FASD research. A highlight of the meeting was the
      presentation of the 2014 Henry Rosett award to Dr. Philip May in recognition of
      his substantial contributions to epidemiological studies on FASD. 

PMID- 25979533
TI  - Men's Report of Domestic Violence Perpetration in Bangladesh: Correlates From a
      Nationally Representative Survey.
AB  - This study provides an examination of the antecedents of domestic violence
      perpetration among a nationally representative sample of men in Bangladesh using
      an ecological model. Secondary analysis of survey data from nationally
      representative Bangladesh Demographic and Health Survey is used to examine
      potential antecedents of perpetration of domestic violence in a sample of 3,371
      ever-married men between the ages of 15 and 54 years. Outcome measure is
      perpetration of domestic violence as measured by a modified Conflict Tactics
      Scale (CTS), and predictor variables include maternal domestic violence,
      egalitarianism, marital age, number of household members, wealth index, marital
      duration, and demographic variables. Men who reported maternal domestic violence
      had 0.13 greater probability of perpetrating domestic violence compared with men
      who did not report maternal domestic violence, men who were egalitarian had 0.04
      greater probability of perpetrating domestic violence compared with men who were
      not egalitarian, men in larger households were less likely to report domestic
      violence. At the same time, the probability of domestic violence perpetration was
      0.07 smaller for men who were married at age 36 years and older, as compared with
      men who were married between the ages of 16 and 20 years, as well as men who were
      married for more than 5 years when compared with men married for 0 to 4 years.
      Finally, the probability of domestic violence perpetration was 0.17 smaller for
      men who were married between the ages of 21 and 25 years and 0.10 smaller for men
      married between the ages of 26 and 35 years, compared with men who married below
      the legal marital age of 21. This study provides support for the use of an
      ecological model to explain domestic violence perpetration in the context of
      Bangladesh to suggest a multipronged holistic effort to address this insidious
      social problem and prevent its intergenerational transmission.

PMID- 25979532
TI  - A prospective randomized, controlled trial deems a drainage of 300 ml/day safe
      before removal of the last chest drain after video-assisted thoracoscopic surgery
      lobectomy.
AB  - OBJECTIVES: To study the feasible and safe volume threshold for chest tube
      removal following video-assisted thoracoscopic surgical lobectomy. METHODS: One
      hundred and sixty-eight consecutive patients (18 were excluded) who underwent
      video-assisted thoracoscopic surgery lobectomy or bilobectomy with two incisions
      between August 2012 and February 2014 were included. Eligible patients were
      randomized into three groups: Group A (chest tube was removed at a drainage
      volume of 150 ml/day or less. n = 49); Group B (chest tube was removed when the
      drainage volume was less than 300 ml/day. n = 50); Group C (chest tube was
      removed when the drainage volume was less than 450 ml/day. n = 51). The
      postoperative care of all patients was consistent. The time of extracting the
      drainage tube, postoperative hospital stay, postoperative visual analogue scale
      grades, dosage of analgesic, and the incidence of complications and
      thoracocentesis were measured. RESULTS: Group B and C had a much shorter drainage
      time and postoperative hospital stay than Group A (P < 0.05). Compared with Group
      B, Group C had a notably shorter drainage time (P = 0.036). The postoperative
      hospital stay was not statistically different between Group B and Group C (P >
      0.05). The mean dosage of pethidine hydrochloride was 248.9 +/- 33.3 mg in Group
      B and 226.1 +/- 32.7 mg in Group C (P > 0.05). The dosage of pethidine
      hydrochloride of Group A was significantly higher than that of Group B and C (P <
      0.05). The total visual analogue scale (VAS) score during the five days showed no
      statistical differences compared with Group B and Group C (P > 0.05), Group A had
      a significantly higher total VAS score than Group B and C (P < 0.05). The number
      of patients who needed thoracentesis in Group C was more than those in Group B
      and A (P < 0.05). There were no statistically significant differences in the
      number of patients who needed reinsertion of chest drains among the three groups
      (P > 0.05). CONCLUSIONS: A 300-ml/day volume threshold for chest tube removal
      after video-assisted thoracoscopic surgery lobectomy is feasible and safe,
      demonstating more advantages than the 150-ml/day volume threshold. However, a 450
      ml/day volume threshold for chest tube removal may increase the risk of
      thoracentesis compared with the 300- and the 150-ml/day volume threshold.

PMID- 25979534
TI  - Athletic Participation and Intimate Partner Violence Victimization: Investigating
      Sport Involvement, Self-Esteem, and Abuse Patterns for Women and Men.
AB  - This study used representative, quantitative data from The National Longitudinal
      Study of Adolescent Health (Add Health) and explored the relationship between
      young adults' sport participation and experiences of intimate partner violence
      victimization (IPVV) for both women and men. Past research has suggested that
      sports participation, especially among women, results in increased self-esteem, a
      prominent protective factor against experiencing IPVV. We found that sports
      participation was associated with a lower prevalence of experiencing IPVV, but
      only for women. In addition, this pattern held after controls for race, mother's
      education, age, number of relationships, and the hypothesized pathways of self
      esteem and alcohol consumption. However, controls for the young adult's own
      education completely mediated the association between sports participation and
      IPVV. Additional analyses indicated that higher education reduced the risk of
      experiencing IPVV and increased the likelihood of sports participation.
      Nonetheless, even among women with the highest educational attainment, sports
      participation was associated with lower prevalence of experiencing IPVV.

PMID- 25979531
TI  - Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal
      exposure to a fat-rich diet.
AB  - Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse
      and suggest that this may result, in part, from the ready access to and intake of
      fat-rich diets. Whereas animal studies show that high-fat diet intake in adults
      can enhance the consumption of either nicotine or ethanol and that maternal
      consumption of a fat-rich diet during pregnancy increases operant responding for
      nicotine in offspring, little is known about the impact of dietary fat on the co
      abuse of these two drugs. The goal of this study was to test in Long-Evans rats
      the effects of perinatal exposure to fat on the co-use of nicotine and ethanol,
      using a novel paradigm that involves simultaneous intravenous (IV) self
      administration of these two drugs. Fat- vs. chow-exposed offspring were
      characterized and compared, first in terms of their nicotine self-administration
      behavior, then in terms of their nicotine/ethanol self-administration behavior,
      and lastly in terms of their self-administration of ethanol in the absence of
      nicotine. The results demonstrate that maternal consumption of fat compared to
      low-fat chow during gestation and lactation significantly stimulates nicotine
      self-administration during fixed-ratio testing. It also increases
      nicotine/ethanol self-administration during fixed-ratio and dose-response
      testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint
      during progressive ratio testing. Of particular note is the finding that rats
      perinatally exposed to fat self-administer significantly more of the
      nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in
      the chow-control rats. After removal of nicotine from the nicotine/ethanol
      mixture, this difference between the fat- and chow-exposed rats was lost, with
      both groups failing to acquire the self-administration of ethanol alone.
      Together, these findings suggest that perinatal exposure to a fat-rich diet, in
      addition to stimulating self-administration of nicotine, causes an even greater
      vulnerability to the excessive co-use of nicotine and ethanol. 

PMID- 25979535
TI  - Women's Perceptions and Experiences of Domestic Violence: An Observational Study
      From Hyderabad, Pakistan.
AB  - This community-based observational study of 1,325 women seen for antenatal care
      examined how women in Pakistan define violence against women (VAW), with an
      emphasis on domestic violence, what an acceptable response to violence is,
      reasons for remaining silent, and whether participants are willing to disclose
      incidents of domestic violence to others. Nearly half of the study participants
      believed that physical violence was VAW. Verbal abuse, controlling behavior by
      the husband, conflict with in-laws, overburdening domestic work, and threatening
      to leave or remarry were also considered VAW. However, only five respondents
      (0.4%) considered sexual abuse to be VAW. Most women who screened positive for
      domestic violence responded by remaining silent or verbal fighting back. None
      sought professional help. Women who decided to remain silent feared that the
      abuse would escalate or that responding would not help them. Women cited social
      stigma and concerns about the impact of the violence on children as reasons for
      not disclosing violent incidents to others or seeking professional help. Women's
      lack of autonomy further reduced their ability to take steps against violence.
      Although societal norms, particularly patriarchal beliefs and women's
      subordination to men, likely explain women's tolerance of abuse, their
      recognition of physical abuse as violence indicates that they do not necessarily
      believe it is always justified. Educational interventions to drive changes in the
      social norms around gender violence along with effective and enforceable legal
      measures are likely required to ensure women's safety.

PMID- 25979536
TI  - The Role of Gender in Violence Experienced by Adults With Developmental
      Disabilities.
AB  - Violence against people with developmental disabilities is a highly prevalent yet
      understudied phenomenon. In particular, there is a paucity of literature
      surrounding the role of gender and the experiences of men. Using a cross
      sectional study design, we surveyed 350 people with diverse developmental
      disabilities about experiences of abuse, perpetrators of abuse, and their
      physical and mental health status. These data were analyzed to determine whether
      gender influenced these domains. Statistical methods included chi-square,
      independent t tests, logistic regression, and hierarchical multiple regressions.
      Male and female participants reported abuse at high rates, with 61.9% of men and
      58.2% of women reporting abuse as children and 63.7% of men and 68.2% of women
      reporting abuse as adults. More women than men reported adult sexual abuse, but
      there was no gender difference in the prevalence of any other form of abuse.
      Women were more likely than men to identify an intimate partner as their abuser,
      although intimate partners represented the minority of abusers for both men and
      women. Violence was associated with worse health status regardless of participant
      gender. These findings confirm that violence is an important issue for both men
      and women with developmental disabilities. Although some expected gender
      differences arose, such as higher rates of adult sexual abuse and intimate
      partner violence against women, these differences were less pronounced than they
      are in the general population, and the overall picture of abuse was one of gender
      similarities rather than differences.

PMID- 25979537
TI  - Rapid quantification of imidazolium-based ionic liquids by hydrophilic
      interaction liquid chromatography: Methodology and an investigation of the
      retention mechanisms.
AB  - The separation of nine N,N'-dialkylimidazolium-based ionic liquids (ILs) by an
      isocratic hydrophilic interaction high-performance liquid chromatographic method
      using an unmodified silica column was investigated. The chosen analytical
      conditions using a 90:10 acetonitrile-ammonium formate buffer mobile phase on a
      high-purity, unmodified silica column were found to be efficient, robust, and
      sensitive for the determination of ILs in a variety of solutions. The retention
      window (k' = 2-11) was narrower than that of previous methods, resulting in a 7
      min runtime for the nine IL homologues. The lower limit of quantification of the
      method, 2-3 MUmol L(-1), was significantly lower than those reported previously
      for HPLC-UV methods. The effects of systematically modifying the IL cation alkyl
      chain length, column temperature, and mobile-phase water and buffer content on
      solute retention were examined. Cation exchange was identified as the dominant
      retention mechanism for most of the solutes, with a distinct (single methylene
      group) transition to a dominant partitioning mode at the highest solute polarity.

PMID- 25979538
TI  - Comprehensive two-dimensional liquid chromatography coupled with quadrupole time
      of-flight mass spectrometry for chemical constituents analysis of tripterygium
      glycosides tablets.
AB  - Comprehensive two-dimensional liquid chromatography platform (LC*LC) coupled with
      quadrupole time-of-flight (QTOF) mass spectrometry (MS) is developed to separate,
      identify and relatively determine the chemical constituents of two types of
      tripterygium glycosides tablets (TGT). The types and relative contents of the
      constituents discovered in two kinds of TGT tablets were subsequently compared.
      C8 and C18 column were used for the separation of the first and second
      dimensional chromatography ((1)D and (2)D) respectively, and an integrated shift
      and full gradient mode was used in (2)D. Using this LC*LC-QTOF-MS platform, 92
      and 132 constituents were detected in TGT preparations from Hubei and Hunan
      manufacturers respectively (HB-TGT and HN-TGT), most of which belonged to the
      diterpenoid, triterpenoid and alkaloid families. 50 and 90 compounds were unique
      in HB-TGT and HN-TGT, respectively, and their relative contents proportion were
      52.0% and 54.2% of HB-TGT and HN-TGT, respectively. Furthermore, two TGT tablets
      could both lead to obvious change in biochemical parameters, oxidative stress
      related parameters and histopathological status to different degree. In all, the
      LC*LC-QTOF-MS platform offer a powerful and efficient method for characterizing,
      identifying and semi-quantifying chemical components in TGT preparations. 

PMID- 25979539
TI  - Adherence to NICE guidelines on diabetes prevention in the UK: Effect on patient
      knowledge and perceived risk.
AB  - BACKGROUND: NICE Guidelines for prevention of diabetes include identifying people
      at risk followed by cost-effective intervention if necessary. Based on assessment
      of risk via a questionnaire and/or blood test the intervention may comprise a
      brief discussion of risk factors and preventive advice or referral to intensive
      lifestyle intervention. DESIGN AND SETTING: In this cross-sectional study 59
      subjects recruited from local GP practices were invited by letter to attend a
      screening for a diabetes prevention study. METHOD: Following a telephone
      screening during which subjects were asked whether they had been informed if they
      were at high-risk of type 2 diabetes, eligible subjects completed a Risk
      Perception Survey for Developing Diabetes (RPS-DD), a validated diabetes risk
      score and underwent an oral glucose tolerance test (OGTT) at a medical screening.
      RESULTS: As measured by the Diabetes UK Risk Score, 44.1% were at high risk,
      42.4% moderate risk and 13.6% at increased risk. 42% of patients had been
      informed they were at high-risk by a health professional. Those who had been
      informed of their risk had significantly higher perceived risk scores (p<0.001),
      higher knowledge scores (p<0.001) and decreased optimism scores (p=0.004), but
      were not more aware that diet (p=0.42) and weight management (p=0.57) can play a
      role in preventing diabetes. CONCLUSIONS: People at high-risk of diabetes are not
      being informed of their risk status as recommended by NICE guidelines. There is
      scope for education for health professionals and the public.

PMID- 25979540
TI  - The highs and lows of targeted therapies.

PMID- 25979542
TI  - Is classical stereotactic radiotherapy the optimal partner for immunotherapy?

PMID- 25979541
TI  - Stereotactic radiation therapy combined with immunotherapy: augmenting the role
      of radiation in local and systemic treatment.
AB  - Stereotactic radiosurgery and stereotactic body radiation therapy are two
      contemporary radiation modalities that can treat tumors in any area of the body
      using highly focused radiation. Recently, immunotherapy has established itself as
      a viable and powerful anticancer treatment. In this review we detail the
      rationale supporting a combination of immunotherapy and stereotactic radiation.
      Additionally, we discuss the evidence for the immune stimulatory effects of
      focused radiation and the role that radiation may play in enhancing the systemic
      treatment effects of immunotherapy. 

PMID- 25979543
TI  - Is radical prostatectomy appropriate for very-high-risk prostate cancer patients?
      Yes.

PMID- 25979544
TI  - Is radical prostatectomy appropriate for very-high-risk prostate cancer patients?
      No.

PMID- 25979545
TI  - Anti-angiogenesis therapy in gynecologic malignancies.
AB  - Anti-angiogenic agents are an important adjuvant treatment strategy in
      gynecologic cancer. Bevacizumab was recently approved for use in advanced
      cervical cancer and platinum-resistant ovarian cancer. The overall survival
      advantage bevacizumab confers in advanced cervical cancer prompted a paradigm
      shift in the standard of care for this disease. Because many other therapeutic
      options are available, and because of the heterogeneity of ovarian malignancies,
      the best combination of chemotherapeutics and bevacizumab has yet to be
      determined; studies are on-going. The utility of bevacizumab in uterine cancer
      has not been consistently demonstrated; current studies are limited to early
      phase clinical trials. Other anti-angiogenic agents, including oral therapies for
      cervical and ovarian cancers, are under investigation; this therapeutic class of
      drugs appears promising. 

PMID- 25979546
TI  - Questions we should be asking about bevacizumab for cervical cancer.

PMID- 25979547
TI  - Treatment of meningioma, including in cases with no further surgical or
      radiotherapy options.

PMID- 25979548
TI  - Subacute headache in a patient with metastatic gastric cancer.

PMID- 25979549
TI  - Immune targeting in breast cancer.
AB  - The immune system is active in breast cancer, playing a dual role in tumor
      progression and in immune surveillance. Infiltrating immune cells are both
      prognostic and predictive of response to standard breast cancer therapies. Breast
      cancer vaccines can activate and expand tumor-specific T cells, but have enjoyed
      minimal clinical success to date. Immune checkpoint blockade is a new approach to
      cancer immunotherapy, with documented clinical responses in diverse tumor types.
      Interest in breast cancer immunotherapy has been reignited by recent reports of
      objective responses in metastatic triple-negative breast cancer with both
      pembrolizumab (a programmed cell death protein 1 [PD-1] antagonist) and MPDL3280A
      (a programmed cell death ligand 1 [PD-L1] antagonist). Rational strategies for
      combination immunotherapy that expand and promote the trafficking of tumor
      specific T cells, support their activity at the tumor site, and abrogate pathways
      of immune suppression within breast tumors are most likely to result in objective
      responses that translate into long-term disease control and cure. 

PMID- 25979550
TI  - Immune targeting in breast cancer: in whom and with what?

PMID- 25979551
TI  - Aspiration Thrombectomy for Treatment of ST-segment Elevation Myocardial
      Infarction: a Meta-analysis of 26 Randomized Trials in 11,943 Patients.
AB  - INTRODUCTION AND OBJECTIVES: There is continued debate about the routine use of
      aspiration thrombectomy in patients with ST-segment elevation myocardial
      infarction. Our aim was to evaluate clinical and procedural outcomes of
      aspiration thrombectomy-assisted primary percutaneous coronary intervention
      compared with conventional primary percutaneous coronary intervention in patients
      with ST-segment elevation myocardial infarction. METHODS: We performed a meta
      analysis of 26 randomized controlled trials with a total of 11 943 patients.
      Clinical outcomes were extracted up to maximum follow-up and random effect models
      were used to assess differences in outcomes. RESULTS: We observed no difference
      in the risk of all-cause death (pooled risk ratio = 0.88; 95% confidence
      interval, 0.74-1.04; P = .124), reinfarction (pooled risk ratio = 0.85; 95%
      confidence interval, 0.67-1.08; P = .176), target vessel revascularization
      (pooled risk ratio = 0.86; 95% confidence interval, 0.73-1.00; P = .052), or
      definite stent thrombosis (pooled risk ratio = 0.76; 95% confidence interval,
      0.49-1.16; P = .202) between the 2 groups at a mean weighted follow-up time of
      10.4 months. There were significant reductions in failure to reach Thrombolysis
      In Myocardial Infarction 3 flow (pooled risk ratio = 0.70; 95% confidence
      interval, 0.60-0.81; P < .001) or myocardial blush grade 3 (pooled risk ratio =
      0.76; 95% confidence interval, 0.65-0.89; P = .001), incomplete ST-segment
      resolution (pooled risk ratio = 0.72; 95% confidence interval, 0.62-0.84; P <
      .001), and evidence of distal embolization (pooled risk ratio = 0.61; 95%
      confidence interval, 0.46-0.81; P = .001) with aspiration thrombectomy but
      estimates were heterogeneous between trials. CONCLUSIONS: Among unselected
      patients with ST-segment elevation myocardial infarction, aspiration thrombectomy
      assisted primary percutaneous coronary intervention does not improve clinical
      outcomes, despite improved epicardial and myocardial parameters of reperfusion.

PMID- 25979552
TI  - Total shoulder arthroplasty using a subscapularis-sparing approach: a
      radiographic analysis.
AB  - BACKGROUND: Traditional total shoulder arthroplasty (TSA) involves releasing the
      subscapularis tendon for exposure. This can potentially lead to subscapularis
      insufficiency, compromised function, and dissatisfaction. A novel TSA technique
      preserves the subscapularis tendon by performing the procedure entirely through
      the rotator interval, allowing accelerated rehabilitation. However, early reports
      on this approach have noted malpositioning of the humeral component and residual
      osteophytes. In a randomized trial, we examined the incidence of humeral head
      malpositioning, incorrect sizing, and residual osteophytes on postoperative
      radiographs after subscapularis-sparing TSA compared with the traditional
      approach. METHODS: Patients were prospectively randomized to undergo TSA
      performed through the traditional or subscapularis-sparing approach. The
      operating surgeon was blinded to the randomization until the day of surgery.
      Anatomic reconstruction measurements included humeral head height, humeral head
      centering, humeral head medial offset, humeral head diameter (HHD), and head-neck
      angle. Two independent reviewers analyzed the postoperative radiographs to
      determine anatomic restoration of the humeral head and the presence of residual
      osteophytes. RESULTS: We randomized 96 patients to undergo either the standard
      approach (n = 50) or the subscapularis-sparing approach (n = 46). There were no
      significant differences in humeral head height, humeral head centering, humeral
      head medial offset, HHD, head-neck angle, and anatomic reconstruction index
      between the 2 groups. However, significantly more postoperative osteophytes (P =
      .0001) were noted in the subscapularis-sparing TSA group. Although the overall
      mean was not statistically different, further analysis of HHD showed that more
      patients in the subscapularis-sparing TSA group were outliers (mismatch >4 mm)
      than in the traditional TSA group. CONCLUSIONS: Although anatomic restoration of
      the shoulder can be accomplished using subscapularis-sparing TSA, retained
      osteophytes and significant mismatch of the HHD raise concerns regarding long
      term outcomes.

PMID- 25979554
TI  - Pectoralis minor tendon in the rotator interval: arthroscopic, magnetic resonance
      imaging findings, and clinical significance.
AB  - BACKGROUND: Although insertional variation of the pectoralis minor on the rotator
      interval has been reported, more detailed characteristics as seen on magnetic
      resonance imaging (MRI) or arthroscopy and clinical significance have been rarely
      discussed. This study evaluated the prevalence of tendinous insertion of the
      pectoralis minor by arthroscopy and diagnostic performances of MRI and suggests
      its clinical implication in rotator cuff repair. MATERIALS AND METHODS: The study
      prospectively recruited 99 consecutive patients for arthroscopic exploration of
      pectoralis minor insertion. Preoperative MRIs were evaluated to detect tendinous
      insertion of the pectoralis minor by 2 independent, blinded observers, and these
      results were correlated with arthroscopy as the gold standard. During
      arthroscopy, the effect of this variation on supraspinatus tendon tear and repair
      was evaluated. RESULTS: Tendinous insertion of the pectoralis minor was found in
      11 patients (11%) at arthroscopy. The sensitivity and specificity of MRI were 64%
      (95% confidence interval [CI], 31%-89%), the specificity was 82% (95% CI, 72%
      89%), and the accuracy was 80% (95% CI, 72%-88%). Intraobserver and interobserver
      reliability tests showed moderate agreements. In 7 patients, it tethered the
      retracted supraspinatus tendon from mobilization and gave rise to tension on the
      repaired cuff, which warranted complete resection of the pectoralis minor tendon
      for a tension-free cuff repair. CONCLUSIONS: Tendinous insertion of the
      pectoralis minor existed with 11% prevalence in our series and could be
      preoperatively detected on MRI. During arthroscopic rotator cuff repair, it can
      be an obstacle to supraspinatus tendon mobilization and repair.

PMID- 25979553
TI  - Propionibacterium acnes infection in shoulder arthroscopy patients with
      postoperative pain.
AB  - BACKGROUND: Recent studies have identified Propionibacterium acnes as the causal
      organism in an increasing number of postoperative shoulder infections. Most
      reports have found a high rate of P acnes infection after open surgery,
      particularly shoulder arthroplasty. However, there are limited data regarding P
      acnes infections after shoulder arthroscopy. MATERIALS AND METHODS: We
      prospectively collected data on all shoulder arthroscopies performed by the
      senior author from January 1, 2009, until April 1, 2013. Cultures were taken in
      all revision shoulder arthroscopy cases performed for pain, stiffness, or
      weakness. In addition, 2 cultures were taken from each of a cohort of 32 primary
      shoulder arthroscopy cases without concern for infection to determine the false
      positive rate. RESULTS: A total of 1,591 shoulder arthroscopies were performed
      during this period, 68 (4.3%) of which were revision procedures performed for
      pain, stiffness, or weakness. A total of 20 revision arthroscopies (29.4%) had
      positive culture findings, and 16 (23.5%) were positive for P acnes. In the
      control group, 1 patient (3.2%) had P acnes growth. CONCLUSIONS: The rate of P
      acnes infection in patients undergoing revision shoulder arthroscopy is higher
      than previously published and should be considered in cases characterized by
      refractory postoperative pain and stiffness.

PMID- 25979555
TI  - The olecranon spur.
AB  - BACKGROUND: There is very little information for today's clinician on olecranon
      spurs. In addition, there is some ambiguity in the literature, with the terms
      "olecranon spur" and "olecranon osteophyte" sometimes being used interchangeably.
      This review presents the current knowledge about olecranon spur anatomy,
      pathophysiology, clinical presentation, diagnosis, treatment options and their
      outcomes, as well as clarification of the terms "spur" and "osteophyte". METHODS:
      The PubMed and Google Scholar databases were searched using the terms "olecranon
      spur," "olecranon traction spur," and "olecranon osteophyte." The resulting
      articles were used to find other manuscripts pertaining to the subject. RESULTS:
      Very few articles were found as a result of these search criteria and were
      limited to a few case reports and a study investigating the postoperative
      outcomes of spur removal. Confusion of the terms "olecranon spur" and "olecranon
      osteophyte" was noted in 6 of the manuscripts. CONCLUSIONS: The mechanism of
      olecranon spur formation has not been confirmed but seems to be similar to that
      of spurs at other entheses. In addition, the current literature represents a
      small number of patients and selects only those who required surgical
      intervention. Three methods of spur resection have been published, and all have
      good outcomes with small patient numbers and limited follow-up.

PMID- 25979556
TI  - Pasteurella multocida infection in a primary shoulder arthroplasty after cat
      scratch: case report and review of literature.

PMID- 25979557
TI  - Superficial Circumflex Iliac Artery Perforator Flap: A Promising Candidate for
      Large Soft Tissue Reconstruction of Retromolar and Lateral Buccal Defects After
      Oncologic Surgery.
AB  - PURPOSE: Surgical reconstruction of extensive retromolar and lateral buccal
      defects after oncologic resection remains a major challenge because early and
      aggressive invasion by retromolar malignancies generally entails wider resection
      of several local anatomic structures to attain tumor-free margins. The
      superficial circumflex iliac artery perforator (SCIP) flap, which is a promising
      candidate with multiple advantages, provides a better choice of quality and
      esthetics for such reconstruction. PATIENTS AND METHODS: Three patients (median
      age, 44.7 yr; age range, 23 to 63 yr) diagnosed with retromolar or lateral buccal
      squamous cell carcinoma (or mucoepidermoid carcinoma) underwent ablative surgery
      and simultaneous SCIP flap reconstruction. Preoperative computed tomographic
      angiographic (CTA) and color ultrasonographic images were used for confirmation
      and positioning of the SCIPs. Volumes of defects and corresponding SCIP flaps
      were recorded and analyzed. In addition, pre- and postoperative functions of
      speech, swallowing, and mouth opening and donor-site morbidity were compared.
      RESULTS: The SCIP flaps were raised according to information gathered from CTA
      and sonographic imaging. The median pedicle length reached 8.2 cm and the flap
      sizes ranged from 5 * 6 to 6.0 * 8.0 cm. All flaps survived uneventfully during
      the perioperative period and subsequent follow-up showed no recurrence.
      Compatible donor-recipient volume, easy harvesting, acceptable postoperative
      functions, and inconspicuous donor-site scars were regarded as the main
      advantages of the SCIP flaps. CONCLUSION: For defects after resection of
      retromolar and lateral buccal tumors, the SCIP flap might play an innovative and
      supplementary role to traditional soft tissue reconstruction approaches.

PMID- 25979558
TI  - End-to-side neurorrhaphy for nerve repair and function rehabilitation.
AB  - BACKGROUND: End-to-side neurorrhaphy is a promising procedure for nerve repair in
      peripheral nerve injury. However, in previous studies, this technique was limited
      to somatic nerves. The present study was designed to investigate the feasibility
      of nerve regeneration after end-to-side neurorrhaphy between autonomic nerve and
      somatic nerve. MATERIALS AND METHODS: Thirty adult male Sprague-Dawley rats were
      randomly divided into the following three groups (n = 10 per group) for different
      treatments: (1) end-to-side neurorrhaphy group, the left L6 and S1 spinal nerves
      were transected in the dura, and the distal stump of L6 ventral root (L6VR) was
      sutured to the lateral face of L4 ventral root (L4VR) through end-to-side
      coaptation; (2) no repair group, the rats received the same operation as the end
      to-side neurorrhaphy group but without coaptation; (3) control group, the rats
      received the same operation as the end-to-side neurorrhaphy group but the L6VR
      was preserved. After 4 month, the origin and mechanism of nerve regeneration were
      evaluated by retrograde nerve tracing. Morphologic and functional properties of
      the regenerated nerve were investigated by morphologic examination and
      intravesical pressure measurement. RESULTS: Retrograde nerve tracing indicated
      that the new neural reflex pathway was successfully established, and the main
      regeneration mechanism was axon collateral sprouting. Morphologic examination and
      intravesical pressure measurement indicated prominent axonal regeneration and
      good bladder functional rehabilitation in the neurorrhaphy group. Wet weight and
      morphology of left extensor digitorum longus muscles appeared no detrimental
      effect on the donor nerve. CONCLUSIONS: These results indicated that the somatic
      motor axons growth into autonomic nerve may be achieved through axon collateral
      sprouting for nerve repair and function rehabilitation after end-to-side
      neurorrhaphy of autonomic nerve and somatic nerve without apparent impairment of
      the donor somatic nerve.

PMID- 25979559
TI  - p38 and interleukin-1 beta pathway via toll-like receptor 4 contributed to the
      skin and muscle incision and retraction-induced allodynia.
AB  - BACKGROUND: Persistent postsurgical pain, as an important clinical problem,
      seriously affects the quality of life in patients. However, the mechanism
      underlying persistent postsurgical pain remains largely unclear. The present
      study aims to elucidate the involvement of toll-like receptor 4 (TLR4) and its
      interaction with p38 and interleukin [IL]-1beta signaling in dorsal root ganglion
      (DRG) in the persistent postsurgical pain. METHODS: Skin and muscle incision and
      retraction (SMIR) surgery-induced paw withdrawal threshold (PWT) change was
      determined by applying mechanical stimuli to the plantar surface of the hind paw
      using von Frey hairs. The PE-10 catheter intrathecal placement was used to
      deliver LPS-RS, interleukin-1 receptor antagonist, or SB203580. Western blot
      analysis was performed to measure the expression of the TLR4, mitogen-activated
      protein kinases family, and IL-1beta in ipsilateral L3 and L4 DRG.
      Immunofluorescence staining was performed to further investigate the cell type of
      TLR4 expression. All data were expressed as means +/- standard error of the mean
      and analyzed using SPSS 13.0. RESULTS: The results showed that the SMIR surgery,
      a rat model of persistent postoperative pain, decreased the ipsilateral 50% PWT,
      and the decrease lasted for at least 20 d. The expression of TLR4 and
      phosphorylation of p38 were upregulated in ipsilateral L3 and L4 DRG neurons
      after SMIR surgery. Pretreatment with LPS-RS, an established TLR4 antagonist,
      prevented p38 activation and attenuated mechanical allodynia induced by SMIR
      surgery. In addition, the expression of IL-1beta was significantly increased
      after SMIR surgery. Blocking IL-1beta by interleukin-1 receptor antagonist
      significantly improved the decreased PWT evoked by SMIR. Moreover, inhibition of
      TLR4 or p38 pathway prevented the IL-1beta upregulation and mechanical allodynia
      induced by SMIR. CONCLUSIONS: These findings suggest that the activation of p38
      and IL-1beta signaling pathway via TLR4 mediate mechanical allodynia after SMIR
      surgery.

PMID- 25979561
TI  - The comparison of saline enema and bisacodyl in rectal preparation before
      anorectal surgery.
AB  - BACKGROUND: Given the limited data on the need of mechanical bowel preparation
      application before anorectal surgeries and the preferred method for bowel
      preparation, we aimed to compare saline enema and bisacodyl in rectal preparation
      before anorectal surgery. MATERIALS AND METHODS: This is a randomized clinical
      trial study. Seventy-nine hospitalized patients for anorectal surgery
      (hemorrhoid, fissure, and fistula) were recruited by convenient sampling and then
      randomly allocated to receive 500 cc Saline by rectal enema or six bisacodyl
      tablets (Sobhan company) beginning from a day before the operation in order to
      prepare the bowel. After surgery, surgeons' satisfaction of the surgery and
      patients' satisfaction of the preparation process were evaluated in the ward
      using Likert score by a nurse blind to the study. Also, the patients were
      interviewed for pain after the first defecation, using numeric rating scale based
      on a 0-10 scores. All patients were actively followed-up after discharge for 1 mo
      concerning postoperative complications. The obtained data were analyzed by SPSS
      software (version 16), Mann-Whitney, chi-squared, and Fisher exact tests at the
      significant level of P < 0/0.5. RESULTS: A total of 79 patients participated in
      the study, 38 received 500-cc saline by rectal enema and 41 bisacodyl tablets. No
      significant differences were observed between the two groups in most variables
      except for pain after the first defecation (P = 0.032). CONCLUSIONS: According to
      the results, the bisacodyl approach results in less pain in the first
      postoperative defecation and fewer complications than the rectal enema. Thus,
      bisacodyl can be suggested as a superior counterpart for enema.

PMID- 25979560
TI  - Prehospital trauma care education for first responders in India.
AB  - BACKGROUND: A major factor contributing to global trauma mortality and morbidity
      is the lack of effective prehospital trauma services in developing settings. We
      developed a 2-d training course for nondoctor first responders featuring high
      fidelity simulation and video-assisted debriefing, self-directed learning videos,
      and native language instruction. MATERIALS AND METHODS: A pilot session was
      conducted in Jodhpur, Rajasthan. Eighteen local instructors were recruited to
      train 48 layperson first responders in 10 essential subjects. Didactic sessions
      of 15-20 min consisting of self-directed learning videos were followed by 30-40
      min skill sessions featuring high-fidelity simulation, and concluded with 15-20
      min video-debriefing periods. Changes in competence were evaluated using
      pretraining and posttraining surveys. RESULTS: Results demonstrated that
      statistically significant competence increases in all areas of trauma management
      assessed: airway (t[46] = 7.30, P < 0.000), hemorrhage (t[46] = 9.96, P < 0.000),
      fractures (t[46] = 9.22, P < 0.000), cervical spine injury (t[46] = 12.12, P =
      0.000), chest injury (t[46] = 7.84, P < 0.000), IV line placement (t[46] = 4.36,
      P < 0.000), extrication (t[46] = 2.81, P < 0.005), scene assessment (t[46] =
      7.06, P < 0.000), triage (t[46] = 5.92, P < 0.000), and communication (t[46] =
      5.56, P < 0.000). Highest increases in competence were observed in cervical spine
      injury and hemorrhage management, with lowest increases in IV line placement and
      extrication. CONCLUSIONS: Results suggest this approach may be effective in
      imparting prehospital trauma management concepts to layperson first responders.
      This study highlights an innovative educational avenue through which trauma
      management capacity can be enhanced in developing settings.

PMID- 25979562
TI  - Protocol for suspected pediatric appendicitis limits computed tomography
      utilization.
AB  - BACKGROUND: Despite radiation concerns, computed tomography (CT) remains the
      favored imaging modality at many children's hospitals for appendicitis. We sought
      to reduce CT utilization for appendicitis in a children's hospital with an
      algorithm relying on 24-h ultrasound (US) as the primary imaging study. MATERIALS
      AND METHODS: An US-based protocol for suspected appendicitis was adopted at the
      end of the fiscal year (FY) 2011. Data were collected for 12 mo before and 24 mo
      after implementation. Imaging test usage and charges were adjusted per annual
      number of appendectomies. Training of emergency department staff continued over 1
      y after protocol implementation. RESULTS: For FY 2011, 644 abdominal CT and 1088
      appendix US were ordered, and 249 laparoscopic appendectomies (LAs) were
      performed. After protocol implementation, FY 2012: 535 CT, 1285 US, and 265 LA
      were performed; and FY 2013: 330 CT, 1235 US, and 236 LA were performed. Length
      of stay decreased from before to after protocol (2.57 +/- 0.29 versus 2.15 +/-
      0.11 d), P < 0.001. CTs per appendectomy decreased 42% from FY 2011 to FY 2013
      (2.43 versus 1.40, P < 0.001) and 30% from before to after protocol (2.43 versus
      1.70, P < 0.001). A corresponding 27% increase in number of US before to after
      protocol (4.11 versus 5.20 US/appendectomy, P = 0.004) occurred. CT and US
      charges decreased $2253 and $6633 per appendectomy for FY 2012 and 2013,
      respectively. CONCLUSIONS: Protocol-driven workup with US significantly reduced
      CT utilization, radiation exposure, and imaging-related charges in children with
      suspected appendicitis. Ongoing training of emergency department staff is
      required to ensure protocol compliance.

PMID- 25979563
TI  - Vasopressin inhibits endotoxin binding in activated macrophages.
AB  - BACKGROUND: Vasopressin possesses potent anti-inflammatory effects. Endotoxin
      recognition (mediated by cluster of differentiation 14 [CD14]), endotoxin
      binding, and subsequent nuclear factor-kappaB (NF-kappaB) activation are
      essential mechanisms for initiation of the inflammatory response. We elucidated
      the effects of vasopressin on these essential mechanisms of inflammation with the
      hypothesis that vasopressin could inhibit CD14 expression, endotoxin binding, and
      NF-kappaB activation in activated macrophages. METHODS: Murine macrophage-like
      cell line RAW264.7 cells were stimulated with endotoxin (lipopolysaccharide
      [LPS]; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL; designated as the LPS and
      the LPS + V groups, respectively). After reaction, between-group differences in
      inflammatory molecule concentrations and levels of NF-kappaB activation,
      endotoxin-macrophages binding, and CD14 expression were compared. Analysis of
      variance was performed for statistical analysis. RESULTS: The concentrations of
      chemokine macrophage inflammatory protein 2 and cytokine interleukin 6 of the LPS
      + V group were significantly lower than those of the LPS group (P = 0.004 and P <
      0.001). The nuclear concentration of phosphorylated NF-kappaB p65 and cytosolic
      concentration of phosphorylated inhibitor-kappaBalpha of the LPS + V group were
      significantly lower than those of the LPS group (all P < 0.05). In addition, the
      level of endotoxin-macrophages binding of the LPS + V group was significantly
      lower than that of the LPS group (P < 0.001). The level of surface CD14
      expression of the LPS + V group was also significantly lower than that of the LPS
      group (P = 0.019). CONCLUSIONS: This study confirmed the potent anti-inflammatory
      effects of vasopressin. The mechanisms underlying the anti-inflammatory effects
      of vasopressin may involve its effects on inhibiting CD14 expression, endotoxin
      binding, and subsequent NF-kappaB activation.

PMID- 25979564
TI  - Combined transpedal and transradial approach for treatment of iliac artery
      chronic total occlusion.
AB  - We present a case of a patient with total chronic occlusion of the right common
      iliac artery that underwent percutaneous stenting with combined transpedal and
      transradial approaches. With this novel strategy, femoral access can be avoided.

PMID- 25979565
TI  - Next generation renal denervation: chemical "perivascular" renal denervation with
      alcohol using a novel drug infusion catheter.
AB  - BACKGROUND/PURPOSE: We update the pre-clinical and early clinical results using a
      novel endovascular approach, to perform chemical renal denervation, via peri
      adventitial injection of micro-doses of dehydrated alcohol (ethanol-EtOH).
      METHODS/MATERIALS: A novel, three-needle delivery device (PeregrineTM) was used
      to denervate the renal arteries of adult swine (n = 17) and in a first-in-man
      feasibility study (n = 18). In the pre-clinical testing EtOH was infused
      bilaterally with one infusion per renal artery into to the perivascular space,
      using EtOH doses of 0.3 ml/artery (n = 8), and 0.6 ml/artery (n = 9), and with
      saline sham control (0.4 ml/artery n = 3). Renal parenchymal norepinephrine (NE)
      concentration (performed blindly), and safety were the primary endpoints. Data
      from the first-in-man study (n = 18) to evaluate device performance, safety and
      peri-procedural pain are reported. RESULTS: In the pre-clinical testing renal
      function was unchanged at 3-month follow-up. Angiography at 90 days (n = 34
      arteries) demonstrated normal appearing renal arteries, unchanged from baseline,
      and without stenosis or other abnormalities. The reductions in mean renal
      parenchymal NE reductions at 3 months were 68% and 88% at doses of 0.3 and 0.6
      ml, respectively (p < 0.001 vs. controls). In the first-in-man study, there was
      100% device success, no complications, a mean treatment time of 4.3 +/- 3
      minutes/artery, and minimal or no patient discomfort during treatment.
      Angiography at 6-months showed no evidence of renal artery stenosis, and evidence
      of a reduction of blood pressure from baseline. CONCLUSION: Perivascular RDN
      using micro-doses of alcohol is a promising alternative to energy-based systems
      to achieve dose-dependent, predictable, safe and essentially painless renal
      denervation. Further clinical evaluation is warranted. SUMMARY: (For annotated
      table of contents) This paper describes the preclinical results, in a porcine
      model, and the early first-in-man results, using the PeregrineTM chemical renal
      denervation catheter to perform renal sympathetic denervation using micro-doses
      of alcohol.

PMID- 25979566
TI  - The effect of a whey protein supplement dose on satiety and food intake in
      resistance training athletes.
AB  - OBJECTIVE: Many athletes perform resistance training and consume dietary protein
      as a strategy to promote anabolic adaptation. Due to its high satiety value, the
      regular addition of supplemented dietary protein could plausibly displace other
      key macronutrients such as carbohydrate in an athlete's diet. This effect will be
      influenced by the form and dose of protein. Therefore, this study assessed the
      impact of liquid whey protein dose manipulation on subjective sensations of
      appetite and food intake in a cohort of athletes. DESIGN: Ten male athletes who
      performed both resistance and aerobic (endurance) training (21.2 +/- 2.3 years;
      181.7 +/- 5.7 cm and 80.8 +/- 6.1 kg) were recruited. In four counter-balanced
      testing sessions they consumed a manipulated whey protein supplement (20, 40, 60
      or 80 g protein) 1 hour after a standardised breakfast. Subsequent energy intake
      was measured 3 hours after the protein supplement using an ad libitum test meal.
      Subjective appetite sensations were measured periodically during the test day
      using visual analogue scales. RESULTS: All conditions resulted in a significant
      decrease in ratings of hunger (50-65%; P < 0.05) at the time of supplement
      consumption. However, there were no significant differences between the
      conditions at any time point for subjective appetite sensations or for energy
      consumed in the ad libitum meal: 4382 +/- 1004, 4643 +/- 982, 4514 +/- 1112, 4177
      +/- 1494 kJ respectively. CONCLUSION: Increasing whey protein supplement dose
      above 20 g did not result in a measurable increase in satiety or decrease in food
      intake. However, the inclusion of additional whey protein supplementation where
      not otherwise consumed could plausibly reduce dietary intake.

PMID- 25979567
TI  - A systematic review of adherence to restricted diets in people with functional
      bowel disorders.
AB  - Functional bowel disorders such as irritable bowel syndrome are commonly
      experienced within the population, and have an adverse impact on emotions,
      physical well-being, social activity, and occupational output. Adherence to a
      restricted diet can reduce symptoms, which in turn leads to increased quality of
      life and well-being. The aim of this review was to assess the extent to which
      predictors of dietary adherence have been considered in studies relating to
      functional bowel disorders and following a restricted diet. This was done firstly
      by examining such studies which contained a measure or indicator of adherence,
      and then by examining predictors of adherence within and between studies. A
      search of PsycINFO, Medline, CINAHL, Web of Science, and Cochrane databases was
      performed during July 2014, with the search criteria including relevant terms
      such as gastrointestinal disorder, irritable bowel syndrome, diet, and adherence.
      Of an initial 7927 papers, 39 were suitable for inclusion. Fourteen of the 39
      studies included had a structured measure or indicator of dietary adherence, and
      the remaining 25 mentioned adherence without any structured levels of adherence.
      There was little investigation into the predictors of adherence, with symptom
      relief or induction being the primary goal of most of the studies. This review
      indicates that predictors of dietary adherence are rarely considered in research
      regarding functional bowel disorders. Further investigation is needed into the
      variables which contribute to rates of adherence to restricted diets, and more
      rigorous research is needed to characterise those individuals most likely to be
      non-adherent. Such research is necessary to ensure that people with these
      conditions can be provided with appropriate support and interventions. 

PMID- 25979568
TI  - Complications, Recovery, and Early Functional Outcomes and Oncologic Control
      Following In-bore Focal Laser Ablation of Prostate Cancer.
AB  - From April 2013 to July 2014, 25 consecutive men participated in a longitudinal
      outcomes study following in-bore magnetic resonance imaging (MRI)-guided focal
      laser ablation (FLA) of prostate cancer (PCa). Eligibility criteria were clinical
      stage T1c and T2a disease; prostate-specific antigen (PSA) <10 ng/ml; Gleason
      score <8; and cancer-suspicious regions (CSRs) on multiparametric MRI harboring
      PCa. CSRs harboring PCa were ablated using a Visualase cooled laser applicator
      system. Tissue temperature was monitored throughout the ablation cycle by proton
      resonance frequency shift magnetic resonance thermometry from phase-sensitive
      images. There were no significant differences between baseline and 3-mo mean
      American Urological Association Symptom Score or Sexual Health Inventory in Men
      scores. No man required pads at any time. Overall, the mean PSA decrease between
      baseline and 3 mo was 2.3 ng/ml (44.2%). Of 28 sites subjected to target biopsy
      after FLA, 26 (96%) showed no evidence of PCa. Our study provides encouraging
      evidence that excellent early oncologic control of significant PCa can be
      achieved following FLA, with virtually no complications or adverse impact on
      quality of life. Longer follow-up is required to show that oncologic control is
      durable. PATIENT SUMMARY: Early results for focal laser ablation of prostate
      cancer are very encouraging. Until long-term oncologic control is demonstrated,
      focal laser ablation must be considered an investigational treatment option.

PMID- 25979569
TI  - Chlorhexidine: a new latex?
AB  - The rate of chlorhexidine (CHX) allergy is increasing. Anaphylaxis is common but
      mild reactions often go unnoticed. Diagnosis is easy to miss, but presentation
      can be severe and can occur at any time during a procedure. Hospitals must have
      management plan for patients who are allergic to CHX. 

PMID- 25979570
TI  - A Four-kallikrein Panel Predicts High-grade Cancer on Biopsy: Independent
      Validation in a Community Cohort.
AB  - BACKGROUND: A statistical model based on four kallikrein markers (total prostate
      specific antigen [tPSA], free PSA [fPSA], intact PSA, and human kallikrein
      related peptidase 2) in blood can predict risk of Gleason score >=7 (high-grade)
      cancer at prostate biopsy. OBJECTIVE: To determine the value of this model in
      predicting high-grade cancer at biopsy in a community-based setting in which
      referral criteria included percentage of fPSA to tPSA (%fPSA). DESIGN, SETTING,
      AND PARTICIPANTS: We evaluated the model, with or without adding blood levels of
      microseminoprotein-beta (MSMB) in a cohort of 749 men referred for prostate
      biopsy due to elevated PSA (>=3 ng/ml), low %fPSA (<20%), or suspicious digital
      rectal examination at Skane University Hospital, Malmo, Sweden. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: The kallikrein markers, with or without
      MSMB levels, measured in cryopreserved anticoagulated blood were combined with
      age in a published statistical model (Prostate Testing for Cancer and Treatment
      [ProtecT]) to predict high-grade cancer at biopsy. Predictive accuracy was
      compared with a base model. RESULTS AND LIMITATIONS: The %fPSA was low (median:
      17; interquartile range: 13-22) in this cohort because this marker was used as a
      referral criterion. The ProtecT model improved discrimination over age and PSA
      for high-grade cancer (0.777 vs 0.720; p=0.002). At one illustrative cut point,
      use of the panel would reduce the number of biopsies by 236 per 1000 and detect
      195 of 208 (94%) but delay diagnosis of 13 of 208 high-grade cancers. MSMB levels
      in blood did not improve the accuracy of the panel (p=0.2). CONCLUSIONS: The
      kallikrein model is predictive of high-grade cancer if criteria for biopsy
      referral also include %fPSA, and it can reduce unnecessary biopsies without
      missing an undue number of tumors. PATIENT SUMMARY: We evaluated a published
      model to predict biopsy outcome in men biopsied due to low percentage of free to
      total prostate-specific antigen. The model helps reduce unnecessary biopsies
      without missing an undue number of high-grade cancers.

PMID- 25979572
TI  - The potential of sec-butylpropylacetamide (SPD) and valnoctamide and their
      individual stereoisomers in status epilepticus.
AB  - sec-Butylpropylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a
      chiral constitutional isomer of valproic acid's (VPA) corresponding amide-
      valpromide. Racemic-SPD and racemic-VCD possess a unique and broad-spectrum
      antiseizure profile superior to that of VPA. In addition, SPD blocks behavioral
      and electrographic status epilepticus (SE) induced by pilocarpine and the
      organophosphates soman and paraoxon. Valnoctamide has similar activity as SPD in
      the soman-induced SE model. The activity of SPD and VCD against SE is superior to
      that of diazepam and midazolam in terms of rapid onset, potency, and ability to
      block SE when given 20 to 60 min after seizure onset. sec-Butylpropylacetamide
      and VCD possess two stereogenic carbons in their chemical structure and, thus,
      exist as a racemic mixture of four individual stereoisomers. The anticonvulsant
      activity of the individual stereoisomers of SPD and VCD was comparatively
      evaluated in several anticonvulsant rodent models including the benzodiazepine
      resistant SE model. sec-Butylpropylacetamide has stereoselective pharmacokinetics
      (PK) and pharmacodynamics (PD). The higher clearance of (2R,3S)-SPD and (2S,3R)
      SPD led to a 50% lower plasma exposure and, consequently, to a lower
      anticonvulsant activity compared to racemic-SPD and its two other stereoisomers.
      Racemic-SPD, (2S,3S)-SPD, and (2R,3R)-SPD have similar anticonvulsant activities
      and PK profiles that are better than those of (2R,3S)-SPD and (2S,3R)-SPD.
      Valnoctamide has a stereoselective PK with (2S,3S)-VCD exhibiting the lowest
      clearance and, consequently, a twice-higher plasma exposure than all other
      stereoisomers. Nevertheless, there was less stereoselectivity in VCD
      anticonvulsant activity, and each stereoisomer had similar ED50 values in most
      models. sec-Butylpropylacetamide and VCD stereoisomers did not cause
      teratogenicity (i.e., neural tube defect) in mice at doses 3-12 times higher than
      their anticonvulsant-ED50 values. This article is part of a Special Issue
      entitled "Status Epilepticus".

PMID- 25979571
TI  - Losartan reverses the down-expression of long noncoding RNA-NR024118 and Cdkn1c
      induced by angiotensin II in adult rat cardiac fibroblasts.
AB  - Angiotensin II (Ang II) plays a pivotal role in the pathogenesis of cardiac
      fibrosis and long noncoding RNAs (lncRNAs) have been found to be involved in
      human diseases. The roles of Ang II receptors (AT1 and AT2) have been
      controversial. Our previous studies revealed that Ang II dynamically down
      regulated the expression of lncRNA-NR024118 and Cdkn1c in adult rat cardiac
      fibroblasts. However, up to now, whether the decrease of lncRNA-NR024118 and
      Cdkn1c induced by Ang II is mediated by AT1 or AT2 has never been illustrated. In
      order to reveal which subtype of Ang II receptors mediate the decrease of lncRNA
      NR024118 and Cdkn1c induced by Ang II, we studied the expression of NR024118 and
      Cdkn1c with different receptor blockers in Ang II-treated adult rat cardiac
      fibroblasts. In this study, we found that losartan (AT1 blocker) nearly
      completely reversed the decrease of lncRNA-NR024118 and partly reversed the
      decrease of Cdkn1c induced by Ang II in adult rat cardiac fibroblasts, while AT2
      blocker (PD123319) did not show effect to the level of lncRNA-NR024118 and
      Cdkn1c. In conclusion, our current studies showed that the decrease of lncRNA
      NR024118 and Cdkn1c induced by Ang II is mediated by AT1 receptor-dependent not
      AT2 receptor-dependent, which is helpful to understand the molecular mechanism of
      Ang II receptors in adult rat cardiac fibroblasts. 

PMID- 25979574
TI  - Comment on: Wollmer P, Engstrom G. Fixed ratio or lower limit of normal (LLN) as
      cut-off value for FEV1/VC: An outcome study. Respiratory Medicine (2013) 107,
      1460-1462.: Fixed ratio or lower limit of normal (LLN) as cut-off value for
      FEV1/VC.

PMID- 25979573
TI  - Type D personality, self-efficacy, and medication adherence in patients with
      heart failure-A mediation analysis.
AB  - BACKGROUND: Type D personality is associated with medication non-adherence. Both
      Type D personality and non-adherence are predictors of poor outcomes. Self
      efficacy, which is modifiable, is also associated with medication adherence.
      OBJECTIVES: To determine the relationships among Type D personality, self
      efficacy, and medication adherence in 84 heart failure patients. METHODS: Self
      efficacy, Type D personality, medication adherence, demographic and clinical data
      were collected. Hierarchical linear regression was used. RESULTS: Type D patients
      were more likely to have lower self-efficacy (p = .023) and medication non
      adherence (p = .027) than non-Type D patients. Low self-efficacy was associated
      with medication non-adherence (p < .001). Type D personality didn't predict
      medication adherence after entering self-efficacy in the model (p = .422),
      demonstrating mediation. CONCLUSIONS: Self-efficacy mediates the relationship
      between Type D personality and medication adherence. Developing and applying
      interventions to enhance self-efficacy may help to sever the link between Type D
      personality and poor outcomes.

PMID- 25979576
TI  - Laser evaporation versus laser excision of oral leukoplakia: A retrospective
      study with long-term follow-up.
AB  - OBJECTIVES: The study makes a comparison between two surgical approaches for the
      treatment of oral leukoplakia (OL) in terms of recurrence in a well-defined
      cohort of patients with a long-term follow-up period. METHODS: The cohort
      consisted of 77 OL patients divided into 2 groups. Group 1: 47 patients treated
      with laser evaporation using a Nd:YAG laser. Group 2: 30 patients treated with a
      CO2 laser for excision. Clinical and histological examinations were performed for
      the diagnosis of OL before treatment. We included OLs with or without dysplasia.
      The mean follow-up period was 60 +/- 32.49 months. RESULTS: Of the 77 patients,
      22 (28.5%) showed recurrence during the follow-up period. No significant
      difference was found between the two treatments (chi(2) = 2.6; p = 0.2). However,
      CO2 laser excision resulted in better results than the Nd:YAG laser evaporation,
      considering the non-homogeneous OLs (chi(2) = 3.9; p = 0.04) and OLs with mild
      dysplasia (chi(2) = 4.6; p = 0.03). DISCUSSION: The study makes a comparison
      between our results and articles from the literature, and suggests when each of
      the two surgical approaches is most appropriate.

PMID- 25979575
TI  - The role of the posterior fossa in developing Chiari I malformation in children
      with craniosynostosis syndromes.
AB  - OBJECTIVE: Patients with craniosynostosis syndromes are at risk of increased
      intracranial pressure (ICP) and Chiari I malformation (CMI), caused by a
      combination of restricted skull growth, venous hypertension, obstructive sleep
      apnea (OSA), and an overproduction or insufficient resorption of cerebrospinal
      fluid. This study evaluates whether craniosynostosis patients with CMI have an
      imbalance between cerebellar volume (CV) and posterior fossa volume (PFV), that
      is, an overcrowded posterior fossa. METHODS: Volumes were measured in 3D-SPGR T1
      weighted MR scans of 28 'not-operated' craniosynostosis patients (mean age: 4.0
      years; range: 0-14), 85 'operated' craniosynostosis patients (mean age: 8.0
      years; range: 1-18), and 34 control subjects (mean age: 5.4 years; range: 0-15).
      Volumes and CV/PFV ratios were compared between the operated and not-operated
      craniosynostosis patients, between the individual craniosynostosis syndromes and
      controls, and between craniosynostosis patients with and without CMI. Data were
      logarithmically transformed and studied with analysis of covariance (ANCOVA).
      RESULTS: The CV, PFV, and CV/PFV ratios of not-operated craniosynostosis patients
      and operated craniosynostosis patients were similar to those of the control
      subjects. None of the individual syndromes was associated with a restricted PFV.
      However, craniosynostosis patients with CMI had a significantly higher CV/PFV
      ratio than the control group (0.77 vs. 0.75; p = 0.008). The range of CV/PFV
      ratios for craniosynostosis patients with CMI, however, did not exceed the normal
      range. CONCLUSION: Volumes and CV/PFV ratio cannot predict which craniosynostosis
      patients are more prone to developing CMI than others. Treatment should focus on
      the skull vault and other contributing factors to increased ICP, including OSA
      and venous hypertension.

PMID- 25979577
TI  - Antibiotic susceptibility of Acinetobacter species in intensive care unit in
      Montenegro.
AB  - The global increase in multidrug resistance of Acinetobacter has created
      widespread problems in the treatment of patients in intensive care units (ICUs).
      The aim of this study was to assess the current level of antimicrobial
      susceptibility of Acinetobacter species in ICU of Clinical Centre of Montenegro
      and determine their epidemiology. Antibiotic susceptibility was tested in 70
      isolates of Acinetobacter collected from non-repeating samples taken from 40
      patients. The first nine isolates were genotyped by repetitive sequence-based PCR
      (rep-PCR). Tigecycline was found to be the most active antimicrobial agent with
      80.6% of susceptibility. All the isolates were multidrug resistant with fully
      resistance to cefalosporinas, piperacillin and piperacillin/tazobactam. More than
      half of them (58.5%) were probably extensively resistant. Seven out of nine
      examined strains were clonally related by rep-PCR. Our results showed extremely
      high rate of multidrug resistance (MDR) of Acinetobacter isolates and high
      percentage of its clonally spreading. 

PMID- 25979578
TI  - Multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, debilitating disease that can have
      devastating effects. Presentation varies widely in symptoms, pace, and
      progression. In addition to a thorough history and physical examination,
      diagnostic tools required to diagnose MS and exclude other diagnoses include MRI,
      evoked potential testing, and cerebrospinal fluid analysis. Although the disease
      is not curable presently, quality of life can be improved by minimizing the
      frequency and severity of disease burden. Disease modification, symptom
      management, preservation of function, and treatment of psychosocial issues are
      paramount to enhance the quality of life for the patient affected with MS. 

PMID- 25979579
TI  - Evaluation and management of amyotrophic lateral sclerosis.
AB  - Motor neuron diseases can cause progressive impairment of voluntary muscles of
      movement, respiration, speech, and swallowing. This review discusses the most
      common motor neuron disease, amyotrophic lateral sclerosis (ALS). It reviews the
      evaluation, diagnosis, and management of ALS, and its epidemiology,
      pathophysiology, and management. A coordinated approach by the primary care
      physician and neurologist is necessary with a focus on treatment options, durable
      medical equipment needs, and end-of-life discussions. 

PMID- 25979580
TI  - Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome and its clinical variants are a group of rapidly
      progressing, potentially debilitating neurologic disorders that may have
      significant morbidity/mortality if left unrecognized or untreated. The most
      common symptoms include ascending limb weakness and paralysis, which may progress
      to respiratory failure. Diagnosis is made clinically with laboratory testing.
      Several treatment options exist, including plasma exchange and intravenous
      immunoglobulin administration. Most cases may resolve without sequelae, but those
      that do not may leave behind significant persistent debility. 

PMID- 25979581
TI  - A practical approach to dementia in the outpatient primary care setting.
AB  - As the population ages, fear of memory loss and potential diagnosis of dementia
      increases. Primary care providers, with their medical knowledge, familiarity with
      patients and their loved ones, and knowledge of the community and its resources,
      are perfectly placed to diagnose and treat commonly presenting types of dementia.
      As knowledge of the types of dementia and their categorization, presentation, and
      course has increased, diagnosis and treatment of this problem have become more
      understandable and amenable to primary care intervention. Diagnosis and work-up
      use common techniques and studies to assist providers. Treatment and management
      have evolved over time to include nonpharmacologic or behavioral interventions. 

PMID- 25979582
TI  - Approach to the patient with Parkinson disease.
AB  - Parkinson disease (PD) is a progressive neurodegenerative disease with motor,
      nonmotor, and behavioral findings. Imaging technology advances have allowed the
      characterization of the underlying pathologic changes to the brain and
      identification of specific lesions in dopaminergic neurons. Although certain
      imaging techniques allow for detection up to 20 years before the onset of motor
      symptoms, these advances have yet to produce meaningful treatments to halt the
      disease or reverse its course. Current treatments are directed at optimizing
      symptomatic management. Referral to a movement disorder specialist familiar with
      PD should be considered for providers with limited familiarity in diagnosis or
      treatment. 

PMID- 25979583
TI  - Epilepsy: current evidence-based paradigms for diagnosis and treatment.
AB  - Although epilepsy has a prevalence of 5 to 7 per 1000 persons in the United
      States, it continues to be a poorly understood condition. Given the number of
      patients in the United States with epilepsy, it is very likely that primary care
      physicians will continue to provide care for these patients. This article
      refreshes some of the knowledge around the diagnosis of epilepsy, discusses
      special populations that may require additional management considerations,
      highlights the association of epilepsy with multiple comorbidities, and discusses
      antiepileptic drug (AED) treatment, including issues surrounding adherence and
      safety of AED therapy. 

PMID- 25979584
TI  - Diagnosis and management of migraines and migraine variants.
AB  - Migraine headache is a neurologic disorder that occurs in 18% of women and 6% of
      men. Adults and children with mild to moderate migraine headaches seeking acute
      therapy should be treated with nonsteroidal anti-inflammatory drugs because of
      the efficacy, cost, and decreased side effects. Some children and adults require
      preventive therapy (those with headaches lasting >12 h, those patients with >4
      headaches in 1 month, those with headaches that affect their ability to
      function). Studies have shown that early treatment with large doses of medication
      work well for the treatment of moderate to severe migraine headache. 

PMID- 25979585
TI  - Sports-related traumatic brain injury.
AB  - Concussions have garnered more attention in the medical literature, media, and
      social media. As such, in the nomenclature according to the Centers for Disease
      Control and Prevention, the term concussion has been supplanted by the term mild
      traumatic brain injury. Current numbers indicate that 1.7 million TBIs are
      documented annually, with estimates around 3 million annually (173,285 sports-
      and recreation-related TBIs among children and adolescents). The Sideline
      Concussion Assessment Tool 3 and the NFL Sideline Concussion Assessment Tool are
      commonly used sideline tools. 

PMID- 25979586
TI  - Office evaluation of dizziness.
AB  - Patients presenting to primary care with complaints of dizziness are common.
      Differentiating the cause of dizziness can be made easier by considering 4 main
      categories of dizziness: vertigo, presyncope/syncope, disequilibrium, and
      nonspecific symptoms. Differentials should immediately include the most common
      causes of dizziness, such as benign paroxysmal positional vertigo and orthostatic
      hypotension. Diagnostic tests should be ordered for patients who have abnormal
      findings on physical examination that may indicate a more serious cause of
      dizziness. 

PMID- 25979587
TI  - Medication- and toxin-induced neurologic syndromes.
AB  - Patients who present with mixed clinical neurologic signs and symptoms can be
      sorted into groups based on the symptom format. Targeted physical examination and
      evaluation of laboratory results can help quickly segment patients into groups
      for further workup or admission. The possibility of medication- or toxin-induced
      neurologic causes must be considered. Medication- and toxin-induced neurologic
      syndrome is a combination of several symptoms that are induced either by the
      exposure to or withdrawal of various medications or by toxins, and the symptoms
      are sometimes difficult to fit into a nice, neat diagnostic package. 

PMID- 25979588
TI  - Neurologic puzzles. Foreword.

PMID- 25979589
TI  - Neurologic diseases: the tragedy and the hope. Preface.

PMID- 25979590
TI  - Radiology Testing in Population Health.

PMID- 25979591
TI  - Re: Development and Utilization of a Web-Based Application as a Robust Radiology
      Teaching Tool (RadStax) for Medical Student Anatomy Teaching.

PMID- 25979592
TI  - Targeted 46-gene and clinical exome sequencing for mutations causing
      cardiomyopathies.
AB  - With the implementation of high-throughput sequencing protocols, the exhaustive
      scanning of known and candidate disease genes has become a feasible approach to
      genetic testing of patients with cardiomyopathy. A primary objective of the
      present study was to assess the performance characteristics of a 46-gene next
      generation sequencing (NGS) assay that targets well-established cardiomyopathy
      genes. A total of 25 samples were analyzed. Twelve of those had previously been
      sequenced using resequencing arrays and served as reference samples for the
      assessment of the assay's performance characteristics. The remaining 13 samples
      were derived from consecutive patients. Both the analytical sensitivity and the
      specificity of the assay were 100% and the percentage of low-coverage bases was
      0.4%, at an average read depth of 210*. In order to assess the diagnostic yield
      of the test, 13 consecutive samples representing cases of Dilated (n = 7),
      Hypertrophic (n = 4) and Left Ventricular Non-Compaction Cardiomyopathy (n = 2),
      were subjected to the 46-gene NGS assay. Including predicted pathogenic variants
      in the gene TTN, a total of 22 variants (11 novel) were detected in 10 patients,
      with a clear preponderance of variants of unknown pathogenicity (class 3
      variants, 21/22, 95%). Of the seven DCM cases, two were digenic, involving
      variants in the genes MYH7 and RBM20 in one case and in DSP and TTN in the other
      case. Three other patients carried single TTN variants predicted to be
      pathogenic. Of the four HCM patients, one was trigenic (LAMA4, PKP2 and TTN) and
      three were digenic (DSP and TTN, MYH7 and NEXN, NEXN and TTN, respectively). As
      to LVNC, one of the two patients had one variant in the gene ABCC9 and two
      predicted pathogenic variants in the gene TTN. Strikingly, out of the thirteen
      investigated cases, only a single case exhibited a likely pathogenic or
      pathogenic variant justifying a positive test report. The percentage of
      inconclusive cases thus amounted to 69%. Three cases were devoid of any relevant
      variant. Two of these "negative" cases were subsequently taken to initially
      evaluate the use of an alternative NGS assay addressing 4813 genes previously
      implicated in genetic diseases (the so-called clinical exome). Although showing
      similar sensitivity and specificity values, the coverage of the 46 established
      cardiomyopathy genes was less efficient (low-coverage bases: 5%). In a case of
      DCM, the assay revealed a disruptive variant in the gene encoding the
      adrenoreceptor beta 2 (ADRB2), a protein implicated in signal transduction and
      energy metabolism in the heart. In conclusion, the 46 gene assay is applicable to
      routine genetic diagnostics of cardiomyopathy. The test detects many variants of
      unknown pathogenicity which need to be followed-up in order to gain benefit for
      the patients and their families. Samples devoid of any relevant variant may be
      subjected to a clinical exome assay, in order to identify interesting novel
      candidate genes.

PMID- 25979593
TI  - An integrated microfluidic chip for the detection of bacteria - A proof of
      concept.
AB  - We designed a microfluidic chip as a proof of concept for the detection of
      bacterial DNA. The chip was fabricated with poly-dimethylsiloxane (PDMS). It
      included a solid phase extraction (SPE) chamber, two separate channels and
      multiple loop-mediated isothermal amplification (LAMP) chambers. Three bacterial
      strains (Escherichia coli O157:H7, methicillin-resistant Staphylococcus aureus
      and methicillin-sensitive S. aureus) were used to test the feasibility of the
      device. LAMP products were examined directly using a UV light and verified by
      agarose gel electrophoresis. Using this chip, we successfully detected E. coli
      O157:H7, MSSA and MRSA in less than 2 h. The detection limit for genes rfbE, spa
      and mecA (specific to E. coli O157:H7, MSSA and MRSA, respectively) was <10(2)
      CFU/100 MUl. Further work is required to refine this approach and rigorously
      assess its analytical and diagnostic specificity and sensitivity.

PMID- 25979594
TI  - Comparison of in vitro methods for carboxylesterase activity determination in
      immortalized cells representative of the intestine, liver and kidney.
AB  - Herein we compare the fluorimetric determination of total and specific
      carboxylesterase activity in immortalized human derived living cells and in cell
      lysates. The cell lines chosen are representative of metabolism occurring in the
      intestine (Caco-2 and HT-29), kidney (HEK-293T) and liver (Hep G2). Caco-2 and HT
      29, as cells prone to differentiation, were tested along the differentiation
      time. For evaluation of both methods when distinguishing activity of different
      carboxylesterases, HEK-293T transfected with the human carboxylestarase-2 (hCES2)
      were also tested. Application to Caco-2 or HT-29 cells demonstrated higher
      activity detected in cell lysates than in cell monolayers. The difference is most
      striking when comparing the methods at different stages of Caco-2 and HT-29 cell
      maturation, highlighting substrate accessibility as a limiting step in the in
      vivo hydrolysis rates (possibly limited by plasma and Endoplasmic Reticulum
      membrane permeability) with increasing relevance as the cells differentiate.
      Application to Hep G2 or to hCES2 transfected and non-transfected HEK-293T cells,
      demonstrated a tendency for higher sensitivity in living cell suspensions than
      that obtained with the cell lysates which indicates the importance of cell
      environment in the maintenance of enzyme activity. However, quantification of
      hCES2 activity relative to total esterase, or to total carboxylesterase activity,
      was not significantly different in any case. The results herein presented help to
      clarify which method is best suited for evaluation of carboxylesterase activity
      in vitro depending on the final goal of the study.

PMID- 25979595
TI  - A 16-gene assay to predict recurrence after surgery in localised renal cell
      carcinoma: development and validation studies.
AB  - BACKGROUND: The likelihood of tumour recurrence after nephrectomy in localised
      clear cell renal cell carcinoma is well characterised by clinical and
      pathological parameters. However, these assessments can be improved and
      personalised by the addition of molecular characteristics of each patient's
      tumour. We aimed to develop and validate a prognostic multigene signature to
      improve prediction of recurrence risk in clear cell renal cell carcinoma.
      METHODS: In the development stage, we investigated the association between
      expression of 732 genes, measured by reverse-transcription PCR, and clinical
      outcome in 942 patients with stage I-III clear cell renal cell carcinoma who had
      undergone a nephrectomy at the Cleveland Clinic (OH, USA). 516 genes were
      associated with recurrence-free interval. 11 of these genes were selected by
      further statistical analyses, and were combined with five reference genes (ie, 16
      genes in total), from which a recurrence score algorithm was developed. The
      recurrence score was then validated in an independent cohort of 626 patients from
      France with stage I-III clear cell renal cell carcinoma who had also undergone
      nephrectomy. The association between the recurrence score and the risk of
      recurrence and cancer-specific survival in the first 5 years after surgery was
      assessed using Cox proportional hazard regression, stratified by tumour stage
      (stage I vs stage II vs III). FINDINGS: In our primary univariate analysis, the
      continuous recurrence score (median 37, IQR 31-45) was significantly associated
      with recurrence-free interval (hazard ratio 3.91 [95% CI 2.63-5.79] for a 25-unit
      increase in score, p<0.0001). In multivariable analyses, the recurrence score was
      significantly associated with the risk of tumour recurrence (hazard ratio per 25
      unit increase in the score 3.37 [95% CI 2.23-5.08], p<0.0001) after
      stratification by stage and adjustment for tumour size, grade, or Leibovich
      score. The recurrence score was able to identify a clinically significant number
      of both high-risk stage I and low-risk stage II-III patients. A heterogeneity
      study on separate samples showed little to no intratumoural variability among the
      16 genes. INTERPRETATION: Our findings validate the recurrence score as a
      predictor of clinical outcome in patients with stage I-III clear cell renal cell
      carcinoma, providing a more accurate and individualised risk assessment beyond
      existing clinical and pathological parameters. FUNDING: Genomic Health Inc and
      Pfizer Inc.

PMID- 25979596
TI  - Prognostication in localised renal cell carcinoma.

PMID- 25979597
TI  - Loss of heterozygosity in tumor tissue in hormonal receptor genes is associated
      with poor prognostic criteria in breast cancer.
AB  - The estrogen receptors (ESRalpha and beta) and the androgen receptor (AR) mediate
      genomic and non-genomic effects on breast tumor growth and proliferation. We
      analyzed 101 breast cancer patients for allelic loss in microsatellites located
      in regulatory regions of the ESRs and AR genes in breast cancer tumors. The loss
      of heterozygosity (LOH) at these loci was found in 36.2% of tumor tissues (ductal
      carcinoma cases), for 19% of cases at the ESRalpha locus, for 16% at the ESRbeta
      locus, and for 10% at the AR locus. The LOH in at least one of the two ESR loci
      was correlated to poor prognosis criteria: ESR-negative status (P = 0.007), PR
      negative status (P = 0.003), high Scarff-Bloom-Richardson (SBR) grade (P =
      0.0007), high MIB-1 proliferation index (P = 0.02), and diminished apoptosis
      potential (TP53-positive status, P = 0.018). When AR was also considered, the LOH
      in at least one of the three loci was associated with ESR-negative status (P =
      0.036), PR-negative status (P = 0.027), high SBR grade (P = 0.005), high mitotic
      index (P = 0.0002), TP53-positive status (P = 0.029), and proliferating index
      (high MIB-1, P = 0.03). Allelic loss was observed in 26% of normal tissue
      adjacent to tumor with LOH at the ESRalpha locus and in 7.1% of tumors with LOH
      at the ESRbeta locus. The LOH in tumor tissue in the regulatory regions of
      ESRalpha, ESRbeta, and AR genes has potentially synergistic effects on tumor
      proliferation, histological aggressiveness, down-regulation of ESRalpha and
      progesterone receptor (PR) genes, and is an early genetic alteration in cancer
      that is possibly involved in passage to estrogen independence. 

PMID- 25979598
TI  - A two-hour antibiotic susceptibility test by ATP-bioluminescence.
AB  - The antibiotic susceptibility test (AST) in Clinical Microbiology laboratories is
      still time-consuming, and most procedures take 24h to yield results. In this
      study, a rapid antimicrobial susceptibility test using ATP-bioluminescence has
      been developed. The design of method was performed using five ATCC collection
      strains of known susceptibility. This procedure was then validated against
      standard commercial methods on 10 strains of enterococci, 10 staphylococci, 10
      non-fermenting gram negative bacilli, and 13 Enterobacteriaceae from patients.
      The agreement obtained in the sensitivity between the ATP-bioluminescence method
      and commercial methods (E-test, MicroScan and VITEK2) was 100%. In summary, the
      preliminary results obtained in this work show that the ATP-bioluminescence
      method could provide a fast and reliable AST in two hours. 

PMID- 25979599
TI  - [Abdominal collection in a patient with Human Inmunodeficieny Virus infection].

PMID- 25979600
TI  - [Rickettsia sibirica mongolitimonae infection in two immunocompetent adults].

PMID- 25979601
TI  - [Facial lesions and acute hepatitis in an Human Immunodeficiency Virus infected
      patient from Paraguay].

PMID- 25979602
TI  - A CXC chemokine gene, CXCL12, from rock bream, Oplegnathus fasciatus: Molecular
      characterization and transcriptional profile.
AB  - Chemokines are small, structurally related chemotactic cytokines characterized by
      the presence of conserved cysteine residues. In the present study, we identified
      the cDNA of a CXC chemokine from Oplegnathus fasciatus, designated as OfCXCL12.
      An open reading frame of 297 bp encoded a 98 amino acid peptide with a putative
      signal peptide of 23 amino acids. The CXC family-specific small cytokine domain
      (SCY), which is highly conserved among vertebrates, was located between residues
      29 and 87. The characteristic conserved cysteine residues in the CXC motif of
      OfCXCL12 were separated by tyrosine (Y). Similar to other vertebrate CXCL12
      proteins, OfCXCL12 also lacked the ELR motif and hence belongs to ELR(-)
      subfamily. Phylogenetic analysis revealed two distinct clades, consisting of fish
      and tetrapod CXCL12 homologs. Constitutive expression with significantly higher
      levels of OfCXCL12 mRNA transcription was detected in immune-related organs,
      including the head kidney, spleen, and kidney. Infection with bacterial and viral
      agents led to significant upregulation of mRNA expression in both the head kidney
      and spleen, in a stimulant-specific manner. Stimulation of peripheral blood
      leukocytes by the mitogen concanavalin-A significantly induced OfCXCL12
      transcription. Results from the present study suggest an important role for
      OfCXCL12 in immune defense against bacterial and viral infection in rock bream.

PMID- 25979603
TI  - Dietary phenylalanine-improved intestinal barrier health in young grass carp
      (Ctenopharyngodon idella) is associated with increased immune status and
      regulated gene expression of cytokines, tight junction proteins, antioxidant
      enzymes and related signalling molecules.
AB  - The present work evaluated the effects of dietary phenylalanine (Phe) on the
      intestinal immune response, tight junction proteins transcript abundance, and the
      gene expression of immune- and antioxidant-related signalling molecules in the
      intestine. In addition, the dietary Phe (and Phe + Tyr) requirement of young
      grass carp (Ctenopharyngodon idella) was also estimated. Fish were fed fish meal
      casein-gelatin based diets (302.3 g crude protein kg(-1)) containing 3.4 (basal
      diet), 6.1, 9.1, 11.5, 14.0 and 16.8 g Phe kg(-1) with a fixed amount of 10.7 g
      tyrosine kg(-1) for 8 weeks. The results showed that Phe deficiency or excess Phe
      reduced the lysozyme and acid phosphatase activities and complement C 3 content
      in the intestine (P < 0.05). Moreover, zonula occludens-1 (ZO-1), occludin and
      claudin c mRNA levels were highest in the fish fed the diet containing 11.5 g Phe
      kg(-1) (P < 0.05). However, claudin 12 and claudin b mRNA levels were not
      significantly affected by dietary Phe (P > 0.05). Gene expression of interleukin
      10 (IL-10), transforming growth factor-beta1 (TGF-beta1), target of rapamycin
      (TOR) and inhibitor of nuclear factor kappaBalpha (IkappaBalpha) in proximal
      intestine (PI), mid intestine (MI) and distal intestine (DI) increased as dietary
      Phe increased up to 6.1, 9.1, 11.5 and 14.0 g kg(-1), respectively (P < 0.05).
      However, interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and
      nuclear factor-kappaB p65 (NF-kappaB p65) mRNA levels showed opposite tendencies.
      In addition, the mRNA level of superoxide dismutase (SOD) was significantly lower
      in the intestinal tissue of the group fed a diet with Phe levels of 16.8 g kg(-1)
      than in those of other groups (P < 0.05). The expression of NF-E2-related factor
      2 (Nrf2) gene was increased as dietary Phe increased up to 9.1 g kg(-1) (P <
      0.05). In conclusion, Phe improved intestinal immune status, and regulated gene
      expression of cytokines, tight junction proteins, antioxidant enzymes, NF-kappaB
      p65, IkappaBalpha, TOR, and Nrf2 in the fish intestine. Based on the quadratic
      regression analysis of lysozyme activity at a 95% maximum, the dietary Phe
      requirement of young grass carp (256-629 g) was estimated to be 8.31 g kg(-1),
      corresponding to 2.75 g 100 g(-1) protein.

PMID- 25979605
TI  - Effect of stimulus and response separation in a matching-to-sample task in the
      brushtail possum (Trichosurus vulpecula).
AB  - This study seeks to investigate the impact of changing the proximity of stimulus
      and response manipulanda on matching-to-sample performance in possums. Possums
      were presented with five rows of blue and yellow stimuli arranged vertically 25mm
      apart above response levers. Generally, peak performance occurred at the distance
      from the lever currently being trained. Performance generalized to distances
      close to the currently trained distance and decreased in accuracy at distances
      further from the trained level. The findings from this experiment provide
      evidence for placing stimuli and response manipulanda close together to improve
      acquisition of a task, and increase the responding accuracy in MTS experiments.
      This suggests that spatial contiguity in the relative location of stimuli and
      response manipulanda is critical to animals performing complex operant tasks. 

PMID- 25979604
TI  - Relative reward effects on operant behavior: Incentive contrast, induction and
      variety effects.
AB  - Comparing different rewards automatically produces dynamic relative outcome
      effects on behavior. Each new outcome exposure is to an updated version evaluated
      relative to alternatives. Relative reward effects include incentive contrast,
      positive induction and variety effects. The present study utilized a novel
      behavioral design to examine relative reward effects on a chain of operant
      behavior using auditory cues. Incentive contrast is the most often examined
      effect and focuses on increases or decreases in behavioral performance after
      value upshifts (positive) or downshifts (negative) relative to another outcome.
      We examined the impact of comparing two reward outcomes in a repeated measures
      design with three sessions: a single outcome and a mixed outcome and a final
      single outcome session. Relative reward effects should be apparent when comparing
      trials for the identical outcome between the single and mixed session types. An
      auditory cue triggered a series of operant responses (nosepoke-leverpress-food
      retrieval), and we measured possible contrast effects for different reward
      magnitude combinations. We found positive contrast for trials with the greatest
      magnitude differential but positive induction or variety effects in other
      combinations. This behavioral task could be useful for analyzing environmental or
      neurobiological factors involved in reward comparisons, decision-making and
      choice during instrumental, goal-directed action. 

PMID- 25979606
TI  - Multistep microsatellite mutation leading to father-child mismatch of FGA locus
      in a case of non-exclusion parentage.
AB  - A non-exclusion paternity case with a mismatch in the autosomal short tandem
      repeats (STR) locus FGA is reported. The genotypes of the suspected father, the
      mother and the questioned child in FGA locus were 18/25, 20/26 and 20/22,
      respectively. Examination of 38 autosomal STR loci revealed no mismatches, and
      the paternity index is up to 1.3618*10(6). The haplotype of 16 Y chromosomal STR
      in the child matched completely with that of the father. These results suggested
      that the suspected father is the biological father of the child and that a rare
      three- or four-step microsatellite mutation had occurred in the paternal allele
      of FGA. 

PMID- 25979607
TI  - Neural correlates of creative thinking and schizotypy.
AB  - Empirical studies indicate a link between creativity and schizotypal personality
      traits, where individuals who score highly on schizotypy measures also display
      greater levels of creative behaviour. However, the exact nature of this
      relationship is not yet clear, with only a few studies examining this association
      using neuroimaging methods. In the present study, the neural substrates of
      creative thinking were assessed with a drawing task paradigm in healthy
      individuals using fMRI. These regions were then statistically correlated with the
      participants' level of schizotypy as measured by the Oxford-Liverpool Inventory
      of Feelings and Experiences (O-LIFE), which is a questionnaire consisting of four
      dimensions. Neural activations associated with the creativity task were observed
      in bilateral inferior temporal gyri, left insula, left parietal lobule, right
      angular gyrus, as well as regions in the prefrontal cortex. This widespread
      pattern of activation suggests that creative thinking utilises multiple
      neurocognitive networks, with creative production being the result of
      collaboration between these regions. Furthermore, the correlational analyses
      found the Unusual Experiences factor of the O-LIFE to be the most common
      dimension associated with these areas, followed by the Impulsive Nonconformity
      dimension. These correlations were negative, indicating that individuals who
      scored the highest in these factors displayed the least amount of activation when
      performing the creative task. This is in line with the idea that 'less is more'
      for creativity, where the deactivation of specific cortical areas may facilitate
      creativity. Thus, these findings contribute to the evidence of a common neural
      basis between creativity and schizotypy. 

PMID- 25979608
TI  - Fronto-parietal and cingulo-opercular network integrity and cognition in health
      and schizophrenia.
AB  - Growing evidence suggests that coordinated activity within specific functional
      brain networks supports cognitive ability, and that abnormalities in brain
      connectivity may underlie cognitive deficits observed in neuropsychiatric
      diseases, such as schizophrenia. Two functional networks, the fronto-parietal
      network (FPN) and cingulo-opercular network (CON), are hypothesized to support
      top-down control of executive functioning, and have therefore emerged as
      potential drivers of cognitive impairment in disease-states. Graph theoretic
      analyses of functional connectivity data can characterize network topology,
      allowing the relationships between cognitive ability and network integrity to be
      examined. In the current study we applied graph analysis to pseudo-resting state
      data in 54 healthy subjects and 46 schizophrenia patients, and measured overall
      cognitive ability as the shared variance in performance from tasks of episodic
      memory, verbal memory, processing speed, goal maintenance, and visual
      integration. We found that, across all participants, cognitive ability was
      significantly positively associated with the local and global efficiency of the
      whole brain, FPN, and CON, but not with the efficiency of a comparison network,
      the auditory network. Additionally, the participation coefficient of the right
      anterior insula, a major hub within the CON, significantly predicted cognition,
      and this relationship was independent of CON global efficiency. Surprisingly, we
      did not observe strong evidence for group differences in any of our network
      metrics. These data suggest that functionally efficient task control networks
      support better cognitive ability in both health and schizophrenia, and that the
      right anterior insula may be a particularly important hub for successful
      cognitive performance across both health and disease. 

PMID- 25979610
TI  - Comparison of two commercial kits and an in-house ELISA for the detection of
      equine rotavirus in foal feces.
AB  - Group A rotaviruses (RVA) are important infectious agents associated with
      diarrhea in the young of several animal species including foals. Currently, a
      variety of diagnosis methods are commercially available, like ELISA, latex
      agglutination and immunochromatographic assays. These commercial tests are mainly
      designed for the detection of human RVA; its applicability in veterinary
      diagnosis has been poorly studied. The aim of this study was to compare the
      sensitivity and specificity of two commercial diagnostic kits, PathfinderTM
      Rotavirus and FASTest Rota(r) strip, with an in-house KERI ELISA, for the
      detection of equine RVA. A total of 172 stool samples from Thoroughbred foals
      with diarrhea were analyzed. The presence of equine RVA in samples in which only
      one of the three methods showed positive results was confirmed by RT-PCR. A
      sample was considered "true positive" when RVA was detected by at least two of
      the methods, and "true negative" when it tested negative by the three assays.
      Following these criteria, 50 samples were found positive and 122 were found
      negative, and were handled as reference population for the assay validation.
      PathfinderTM Rotavirus assay showed 32% sensitivity and 97% specificity, FASTest
      Rota(r) strip, 92% sensitivity and 97% specificity, and KERI ELISA, 76%
      sensitivity and 93% specificity. PathfinderTM Rotavirus showed 77%, FASTest
      Rota(r) strip 95%, and KERI ELISA 88% accuracy to correctly classify the samples
      as equine RVA positive or negative. Pathfinder failed specifically to detect
      equine RVA G3P12I6 genotype; such performance might be related to the specificity
      of the monoclonal antibody included in this kit. According to our results,
      differences among VP6 genotypes could influence the sensitivity to detect equine
      RVA in foal feces, and thus assay validation of diagnostic kits for each species
      is necessary. In conclusion, FASTest Rota(r) strip is more suitable than ELISA
      PathfinderTM Rotavirus for the screening of rotavirus infection in foals. The
      KERI ELISA showed an acceptable performance, and could be considered a proper
      economic alternative for equine RVA diagnosis. 

PMID- 25979609
TI  - Neuroticism modulates the effects of intranasal vasopressin treatment on the
      neural response to positive and negative social interactions.
AB  - Neuroticism is a fundamental personality trait associated with proneness to feel
      negative affect. Here we ask how Neuroticism influences the neural response to
      positive and negative social interactions and how Neuroticism modulates the
      effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response
      to social interactions. In a double-blind, placebo-controlled study, 153 male
      participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or
      placebo. Afterwards, they were imaged with fMRI while playing an iterated
      Prisoner's Dilemma Game. On a different day, subjects completed the NEO
      personality inventory to measure Neuroticism. Neuroticism was positively
      correlated with the neural response to negative social interactions in the
      anterior cingulate cortex/medial prefrontal cortex and with the neural response
      to positive social interactions in the insula, indicating that Neuroticism
      modulates neuropsychological processing of both negative and positive social
      interactions. Neuroticism did not modulate the effect of intranasal OT treatment
      on the neural response to either positive or negative social interactions. On the
      other hand, AVP treatment significantly interacted with Neuroticism to modulate
      the BOLD response to both positive and negative social interactions.
      Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex
      and lateral temporal lobe responses to negative social interactions to a greater
      extent in participants scoring high rather than low on Neuroticism. AVP also
      increased the insula response to positive social interactions to a greater extent
      in participants scoring high rather than low on Neuroticism. These results imply
      that AVP may increase emotion regulation in response to negative social
      interactions and the salience of positive social interactions to a greater extent
      in individuals high compared to low in Neuroticism. The current findings urge
      caution against uniform clinical application of nonapeptides and suggest that
      their efficacy may vary as a function of personality.

PMID- 25979611
TI  - Aporocotyle michaudi n. sp. (Digenea: Aporocotylidae) from the emerald rock cod,
      Trematomus bernacchii (Teleostei: Perciformes) in Antarctica.
AB  - Aporocotyle michaudi n. sp. is described from the gill blood vessels of the
      emerald rock cod Trematomus bernacchii in the Ross Sea, Antarctica. It is
      distinguished from all other species of Aporocotyle by its body tegument showing
      single conical spines, spinous buccal capsule, and genital atrium positioned
      medially; all congeners described to date are characterized by clusters of
      tegumental spines, unspined buccal capsule and genital atrium located in the
      lateral part of the body. Aporocotyle michaudi n. sp. clearly differs from A.
      notothenia (the only other species of Aporocotyle found in a perciform fish) in
      its shape and arrangement of tegumental spines, buccal capsule features, location
      of genital atrium, body size, ratio of esophagus/body length, anterior
      caeca/posterior caeca ratio, number of testes, cirrus sac and ovary size and
      shape, and host. The new species is easily distinguished from A. argentinensis
      (the species that most closely resembles A. michaudi) by the shape and
      arrangement of tegumental spines, buccal capsule features, genital atrium
      location, left anterior caecum longer than right, esophagus/body length ratio,
      number of testes, cirrus sac size and shape, host and molecular analyses.
      Phylogenetic analyses of partial 28S rDNA genetic data showed that sequences
      representing the new species form a distinct clade with all other sequences for
      species of Aporocotyle and appear basal within the genus. Aporocotyle michaudi n.
      sp. represents the only species of genus described in Antarctica. 

PMID- 25979612
TI  - Raphidascaris (Raphidascaris) macrouri n. sp. (Nematoda: Anisakidae) from two
      deep-sea macrourid fishes in the Western Mediterranean: Morphological and
      molecular characterisations.
AB  - A new nematode species, Raphidascaris (Raphidascaris) macrouri n. sp.
      (Anisakidae), is described from male and female specimens found in the intestine,
      and occasionally in stomach and pyloric caeca, of two deep-water macrourid fishes
      (Gadiformes) off Barcelona, Mediterranean Sea: Nezumia aequalis (Gunther) (type
      host) and Trachyrincus scabrus (Rafinesque). Based on light and scanning electron
      microscopy examination, the new species shows similar morphological features as
      the other four valid species of the subgenus Raphidascaris Railliet & Henry,
      1915, but it differs from Raphidascaris (Raphidascaris) acus (Bloch, 1779),
      Raphidascaris (Raphidascaris) lutjani Olsen, 1952 and Raphidascaris
      (Raphidascaris) mediterraneus Lebre & Petter, 1983 in the high number of
      precloacal papillae (23-32) and from Raphidascaris (Raphidascaris) gigi Fujita,
      1928 in the length of the spicules. Moreover, Raphidascaris (Raphidascaris)
      macrouri n. sp. exhibits a high variability on the number and distribution of
      caudal papillae, which was not recorded in the other four mentioned species. This
      is the first species of this subgenus reported from the family Macrouridae.
      Sequences of ITS1-5.8S-ITS2 region are analysed and compared with closely related
      nematode species. Molecular analysis confirmed the uniformity of the R. (R.)
      macrouri n. sp. between hosts. 

PMID- 25979613
TI  - A recurrent granulosa cell tumor of the ovary 25 years after the initial
      diagnosis: A case report.
AB  - INTRODUCTION: Granulosa cell tumors (GCTs) are rare functional sex-cord-stromal
      ovarian neoplasms characterized by low malignancy potential and late relapse,
      which rarely metastasize to the liver. PRESENTATION OF CASE: A 43-year-old
      female, who had undergone surgery to treat a GCT of the left ovary in 1976,
      complained of abdominal distention in May 2001. Imaging studies demonstrated
      masses in the right lobe of the liver, together with massive ascites. The
      patient's bloody ascites showed no cytological evidence of malignancy. A
      diagnostic laparoscopy was performed, and the biopsy specimen was histologically
      proven to be a recurrent granulosa cell tumor. The patient was successfully
      treated surgery followed by systemic chemotherapy. Her postoperative course was
      uneventful and systemic chemotherapy was repeated due to the suspicion of a
      recurrence in the pelvic cavity. DISCUSSION: GCTs which are rare malignant tumors
      of the ovary, tend to be associated with late recurrence. Although most
      recurrences occur within 10 years after the initial diagnosis, there are
      occasional reports of recurrences after 10 years have been. We experienced the
      rare case of a patient who relapsed 25 years after the initial diagnosis.
      CONCLUSION: The long natural history of this disease highlights the importance of
      extended follow up for GCT patients. In addition, aggressive therapy including
      surgery and chemotherapy may contribute to a patient's long-term prognosis.

PMID- 25979615
TI  - HIV-serodiscordant couples desiring a child: 'treatment as prevention,'
      preexposure prophylaxis, or medically assisted procreation?
AB  - OBJECTIVE: We sought to assess the residual risk of HIV transmission, cost, and
      cost-effectiveness of various strategies that can help fertile HIV-uninfected
      female/HIV-1-infected male on combination antiretroviral therapy with plasma HIV
      RNA <50 copies/mL couples to have a child: (1) unprotected sexual intercourse
      (treatment as prevention); (2) treatment as prevention limited to fertile days
      (targeting fertile days); (3) treatment as prevention with preexposure
      prophylaxis (tenofovir/emtricitabine); (4) treatment as prevention and
      preexposure prophylaxis limited to fertile days; or (5) medically assisted
      procreation (MAP). STUDY DESIGN: This was a model-based, cost-effectiveness
      analysis performed from a French societal perspective. Input parameters derived
      from international literature included: 85% probability of live births in
      different strategies, 0.0083%/mo HIV transmission risk with unprotected vaginal
      intercourse, 1% HIV mother-to-child transmission rate, and 4.4% birth defect risk
      related to combination antiretroviral therapy when the mother is infected at
      conception. Targeting fertile days and preexposure prophylaxis were estimated to
      decrease the risk of HIV transmission by 80% and 67%, respectively, and by 93.4%
      for preexposure prophylaxis limited to fertile days (the relative risk of
      transmission considering the combination of both strategies assuming to be (1
      80%)*(1-67%) = 16.6% in basecase). Tenofovir/emtricitabine monthly cost was set
      at ?540. RESULTS: The HIV transmission risk was highest with treatment as
      prevention and lowest for MAP (5.4 and 0.0 HIV-infected women/10,000 pregnancies,
      respectively). Targeting fertile days was more effective than preexposure
      prophylaxis (0.9 vs 1.8) and associated with lowest costs. Preexposure
      prophylaxis limited to fertile days was more effective than targeting fertile
      days (0.3 vs 0.9) with a cost-effectiveness ratio of ?1,130,000/life year saved;
      MAP cost-effectiveness ratio when compared with preexposure prophylaxis limited
      to fertile days was ?3,600,000/life year saved. Results were robust to multiple
      sensitivity analyses. CONCLUSION: Targeting fertile days is associated with a low
      risk of HIV transmission in fertile HIV-uninfected female/male with controlled
      HIV-1 infection couples. The risk is lower with preexposure prophylaxis limited
      to fertile days, or MAP, but these strategies are associated with unfavorable
      cost-effectiveness ratios under their current costs.

PMID- 25979614
TI  - 17-hydroxyprogesterone caproate for preterm rupture of the membranes: a
      multicenter, randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Preterm rupture of membranes (PROM) is associated with an increased
      risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone
      caproate (17OHP-C) reduces the risk of preterm birth in some women who are at
      risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy
      or improve perinatal outcome when given to mothers with preterm rupture of the
      membranes. STUDY DESIGN: This is a multicenter, double-blind, placebo-controlled,
      randomized clinical trial. The study included singleton pregnancies with
      gestational ages from 23(0/7) to 30(6/7) weeks at enrollment, documented PROM,
      and no contraindication to expectant management. Consenting women were assigned
      randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or
      placebo. The primary outcome was continuation of pregnancy until a favorable
      gestational age, which was defined as either 34(0/7) weeks of gestation or
      documentation of fetal lung maturity at 32(0/7) to 33(6/7) weeks of gestation.
      The 2 prespecified secondary outcomes were interval from randomization to
      delivery and composite adverse perinatal outcome. The planned sample size was 222
      total women. RESULTS: From October 2011 to April 2014, 152 women were enrolled;
      74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to
      placebo. The trial was stopped when results of a planned interim analysis
      suggested that continuation was futile. The primary outcome was achieved in 3% of
      the 17OHP-C group and 8% of the placebo group (P = .18). There was no significant
      between-group difference in the prespecified secondary outcomes, randomization-to
      delivery interval (17.1 +/- 16.1 vs 17.0 +/- 15.8 days, respectively; P = .76) or
      composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No
      significant differences were found in other outcomes, which included rates of
      chorioamnionitis, postpartum endometritis, cesarean delivery, individual
      components of the composite outcome, or prolonged neonatal length of stay.
      CONCLUSION: Compared with placebo, weekly 17OHP-C injections did not prolong
      pregnancy or reduce perinatal morbidity in patients with PROM in this trial.

PMID- 25979616
TI  - Pregnancy-related cardiovascular deaths in California: beyond peripartum
      cardiomyopathy.
AB  - OBJECTIVE: Maternal mortality rates rose markedly from 2002 to 2006 in
      California, prompting an in-depth maternal mortality review in a state that
      comprises one twelfth of the US birth cohort. Cardiovascular disease has emerged
      as the leading cause of pregnancy-related death in the United States. The primary
      aim of this analysis was to describe the incidence and type of cardiovascular
      disease as a cause of pregnancy-related mortality in California. The secondary
      aims were to describe racial/ethnic and socioeconomic disparities, risk factors,
      birth outcomes, timing of death and diagnosis, and signs and symptoms of
      cardiovascular disease and identify contributing factors. STUDY DESIGN: The
      California Pregnancy-Associated Mortality Review retrospectively examined a case
      series of 64 cardiovascular pregnancy-related deaths from 2002 through 2006. Two
      cardiologists independently reviewed complete inpatient and outpatient medical
      records including laboratory, radiology, electrocardiogram, chest X-ray,
      echocardiograms, and autopsy findings for each cardiovascular death and
      classified cause of death by type of cardiovascular disease. Demographic data,
      racial disparities, risk factors, signs and symptoms, timing of diagnosis and
      death, birth outcomes, and contributing factors were analyzed using bivariate
      comparisons with noncardiovascular pregnancy-related deaths and population-based
      data. RESULTS: Among 2,741,220 California women who gave birth, 864 died while
      pregnant or within 1 year of pregnancy; 257 of the deaths were deemed pregnancy
      related, and of these, 64 (25%) were attributed to cardiovascular disease. There
      were 42 deaths caused by cardiomyopathy, and the pregnancy-related mortality rate
      from cardiomyopathy was 1.54 per 100,000 births. Dilated cardiomyopathy existed
      in 29 cases, of which 15 met the definition of peripartum cardiomyopathy. Women
      with cardiovascular disease were more likely than women who died from
      noncardiovascular causes to be African-American (39.1% vs 16.1%; P < .01) and
      more likely to use illicit substances (23.7% vs 9.4%; P < .01). Thirty-seven
      percent were obese and 20% had a concomitant diagnosis of hypertension or
      preeclampsia during pregnancy. Health care decisions in the diagnosis or
      treatment of cardiovascular disease during and after pregnancy contributed to the
      fatal outcomes. CONCLUSION: African-American race, substance use, and obesity
      were risk factors for pregnancy-related cardiovascular disease mortality. Chronic
      disease prevention and better recognition and response to cardiovascular disease
      during pregnancy are needed to reduce maternal mortality.

PMID- 25979617
TI  - Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in
      singleton and twin pregnancies.
AB  - OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is known to be associated
      with fetal complications. It recently was suggested to be associated possibly
      with preeclampsia (PET) as well. The objective of this study was to investigate
      that possibility. STUDY DESIGN: The study group included 78 women (54 singleton
      and 24 twin pregnancies) who had been diagnosed with ICP based on clinical
      presentation, elevated liver enzymes, and elevated total bile acids (>10
      MUmol/L). Disease severity was based on total bile acids levels as being severe
      (>40 MUmol/L), moderate (20-40 MUmol/L), or mild (10-20 MUmol/L). The course of
      disease was reviewed carefully in each case. The control groups were comprised of
      apparently healthy women with singleton (n = 200) and twin (n = 100) pregnancies
      that were drawn randomly from a computerized registry of all the deliveries in
      our institution during the study period. RESULTS: The total incidence of PET was
      significantly higher for the patients with ICP who had singleton and twin
      pregnancies compared with the control groups (singletons: 7.4% vs 1.5%; P < .05;
      twins: 33.3% vs 6.2%; P < .05, respectively). The incidence of severe PET was
      also significantly higher in both singleton (11-fold) and twin (8-fold)
      pregnancies compared with control subjects. Severe ICP, but not mild ICP, was a
      major risk factor for PET among women with either singleton or twin pregnancies.
      The timing of the initial presentation of ICP had no effect on PET incidence
      rates. Preeclampsia occurred usually 2-4 weeks after the diagnosis of ICP, and
      proteinuria preceded elevated blood pressure in all cases. Moreover, the total
      bile acid levels among 33 women who were diagnosed as having PET, but not ICP,
      were within normal range. CONCLUSION: ICP increases the incidence of PET; severe
      disease was a major risk factor for preeclampsia. Therefore, we strongly suggest
      including routine evaluation for preeclampsia in the treatment of women with
      moderate and severe ICP.

PMID- 25979618
TI  - Pregnancy-induced adaptations in the intrinsic structure of rat pelvic floor
      muscles.
AB  - OBJECTIVE: Maternal birth trauma to the pelvic floor muscles (PFMs) is a major
      risk factor for pelvic floor disorders. Modeling and imaging studies suggest that
      demands placed on PFMs during childbirth exceed their physiologic limits; however
      many parous women do not sustain PFM injury. Here we determine whether pregnancy
      induces adaptations in PFM architecture, the strongest predictor of muscle
      function, and/or intramuscular extracellular matrix (ECM), responsible for load
      bearing. To establish if parallel changes occur in muscles outside of the PFM, we
      also examined a hind limb muscle. STUDY DESIGN: Coccygeus, iliocaudalis,
      pubocaudalis, and tibialis anterior of 3-month-old Sprague-Dawley virgin, mid
      pregnant, and late-pregnant; 6-month-old virgin; and 4- and 12-week postpartum
      rats (N = 10/group) were fixed in situ and harvested. Major architectural
      parameters determining muscle's excursion and force-generating capacity were
      quantified, namely, normalized fiber length (Lfn), physiologic cross-sectional
      area, and sarcomere length. Hydroxyproline content was used as a surrogate for
      intramuscular ECM quantity. Analyses were performed by 2-way analysis of variance
      with Tukey post hoc testing at a significance level of .05. RESULTS: Pregnancy
      induced a significant increase in Lfn in all PFMs by the end of gestation
      relative to virgin controls. Fibers were elongated by 37% in coccygeus (P <
      .0001), and by 21% in iliocaudalis and pubocaudalis (P < .0001). Importantly, no
      Lfn change was observed in the tibialis anterior. Physiologic cross-sectional
      area and sarcomere length were not affected by pregnancy. By 12 weeks'
      postpartum, Lfn of all PFMs returned to the prepregnancy values. Relative to
      virgin controls, ECM increased by 140% in coccygeus, 52% in iliocaudalis, and 75%
      in pubocaudalis in late-pregnant group, but remained unchanged across time in the
      tibialis anterior. Postpartum, ECM collagen content returned to prepregnancy
      levels in iliocaudalis and pubocaudalis, but continued to be significantly
      elevated in coccygeus (P < .0001). CONCLUSION: This study demonstrates that
      pregnancy induces unique adaptations in the structure of the PFMs, which adjust
      their architectural design by adding sarcomeres in series to increase fiber
      length as well as mounting a substantial synthesis of collagen in intramuscular
      ECM.

PMID- 25979620
TI  - Epigenetics of Posttraumatic Stress Disorder: Current Evidence, Challenges, and
      Future Directions.
AB  - Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder
      that is thought to emerge from complex interactions among traumatic events and
      multiple genetic factors. Epigenetic regulation lies at the heart of these
      interactions and mediates the lasting effects of the environment on gene
      regulation. An increasing body of evidence in human subjects with PTSD supports a
      role for epigenetic regulation of distinct genes and pathways in the pathogenesis
      of PTSD. The role of epigenetic regulation is further supported by studies
      examining fear conditioning in rodent models. Although this line of research
      offers an exciting outlook for future epigenetic research in PTSD, important
      limitations include the tissue specificity of epigenetic modifications, the
      phenomenologic definition of the disorder, and the challenge of translating
      molecular evidence across species. These limitations call for studies that
      combine data from postmortem human brain tissue and animal models, assess
      longitudinal epigenetic changes in living subjects, and examine dimensional
      phenotypes in addition to diagnoses. Moreover, examining the environmental,
      genetic, and epigenetic factors that promote resilience to trauma may lead to
      important advances in the field. 

PMID- 25979619
TI  - An animal model for chorioamnionitis at term.
AB  - OBJECTIVE: The purpose of this study was to develop an animal model for
      intrapartum inflammation at term to investigate the interactions between maternal
      and fetal inflammatory responses and adverse neurologic outcome. STUDY DESIGN:
      Lipopolysaccharide (160, 320, or 640 MUg/kg) was administered intraperitoneally
      to day 20 term-pregnant Sprague Dawley rat dams 2, 4, and 6 hours before sample
      collection. Maternal outcomes included dam core temperature and plasma
      interleukin 6 (IL-6). Fetal outcomes included plasma IL-6, brain IL-6 messenger
      RNA expression, and brain IL-6 protein expression. Primary cortical cell cultures
      were prepared to examine neuronal morphologic condition. Neurite counts were
      obtained with the use of automated Sholl analysis. RESULTS: Maternal plasma IL-6
      levels peaked 2 hours after lipopolysaccharide stimulus and rapidly resolved,
      except for an observed low level persistence at 6 hours with 640 MUg/kg. Fetal
      plasma and placental IL-6 expression also peaked rapidly but only persisted in
      placental samples. Fetal brain IL-6 RNA and protein expression was significantly
      higher than control litters at 6 hours after the exposure to both 320 MUg/kg (P
      <= .05) and 640 MUg/kg (P <= .01). Cortical cells from fetuses that were exposed
      for 6 hours to maternal systemic inflammation showed reduced neurite number and
      neurite length (P < .001) with increasing lipopolysaccharide dose. CONCLUSION:
      Our results demonstrate that fetal brain injury follows isolated systemic
      maternal inflammation and that fetal brain inflammation lags after maternal
      stimulus, which creates a potential 4-hour clinical window for therapeutic
      intervention.

PMID- 25979622
TI  - Rebuttal to the criticism on the paper "Application of Mn/MCM-41 as an adsorbent
      to remove Methyl Blue from aqueous solution".

PMID- 25979621
TI  - Chronic Cigarette Smoking in Healthy Middle-Aged Individuals Is Associated With
      Decreased Regional Brain N-acetylaspartate and Glutamate Levels.
AB  - BACKGROUND: Cigarette smoking is associated with metabolite abnormalities in
      anterior brain regions, but it is unclear if these abnormalities are apparent in
      other regions. Additionally, relationships between regional brain metabolite
      levels and measures of decision making, risk taking, and impulsivity in smokers
      and nonsmokers have not been investigated. METHODS: In young to middle-aged
      (predominately male) nonsmokers (n = 30) and smokers (n = 35), N-acetylaspartate
      (NAA), choline-containing compounds, creatine-containing compounds (Cr), myo
      inositol (mI), and glutamate (Glu) levels in the anterior cingulate cortex and
      right dorsolateral prefrontal cortex (DLPFC) were compared via 4-tesla proton
      single volume magnetic resonance spectroscopy. Groups also were compared on NAA,
      choline-containing compounds, Cr, and mI concentrations in the gray matter and
      white matter of the four cerebral lobes and subcortical nuclei/regions with 1.5
      tesla proton magnetic resonance spectroscopy. Associations of regional metabolite
      levels with neurocognitive, decision-making, risk-taking, and self-reported
      impulsivity measures were examined. RESULTS: Smokers showed lower DLPFC NAA, Cr,
      mI and Glu concentrations and lower lenticular nuclei NAA level; smokers also
      demonstrated greater age-related decreases of DLPFC NAA and anterior cingulate
      cortex and DLPFC Glu levels. Smokers exhibited poorer decision making and greater
      impulsivity. Across the sample, higher NAA and Glu in the DLPFC and NAA
      concentrations in multiple lobar gray matter and white matter regions and
      subcortical nuclei were associated with better neurocognition and lower
      impulsivity. CONCLUSIONS: This study provides additional novel evidence that
      chronic smoking in young and middle-aged individuals is associated with
      significant age-related neurobiological abnormalities in anterior frontal regions
      implicated in the development and maintenance of addictive disorders.

PMID- 25979623
TI  - An unusual cause of limp.

PMID- 25979624
TI  - The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver
      metastases: Clinical risk score as possible discriminator.
AB  - AIM: The combination of surgery and chemotherapy (CTx) is increasingly accepted
      as an effective treatment for patients with colorectal liver metastases (CRLM).
      However, controversy exists whether all patients with resectable CRLM benefit
      from perioperative CTx. We investigated the impact on overall survival (OS) by
      neo-adjuvant CTx in patients with resectable CRLM, stratified by the clinical
      risk score (CRS) described by Fong et al. METHODS: Patients who underwent surgery
      for CRLM between January 2000 and December 2009 were included. We compared OS of
      patients with and without neo-adjuvant CTx stratified by the CRS. The CRS
      includes five prognosticators and defines two risk groups: low CRS (0-2) and high
      CRS (3-5). RESULTS: 363 patients (64% male) were included, median age 63 years
      (IQR 57-70). Prior to resection, 219 patients had a low CRS (neo-adjuvant CTx: N
      = 65) and 144 patients had a high CRS (neo-adjuvant CTx: N = 88). Median follow
      up was 47 months (IQR 25-82). In the low CRS group, there was no significant
      difference in median OS between patients with and without CTx (65 months (95% CI
      39-91) vs. 54 months (95% CI 44-64), P = 0.31). In the high CRS group, there was
      a significant difference in OS between patients with and without CTx (46 months
      (95% CI 24-68) vs. 33 month (95% CI 29-37), P = 0.004). CONCLUSION: In our
      series, patients with a high CRS benefit from neo-adjuvant CTx. In patients with
      a low risk profile, neo-adjuvant CTx might not be beneficial.

PMID- 25979626
TI  - Impact of lung function interpretation approach on pediatric bronchiolitis
      obliterans syndrome diagnosis after lung transplantation.
AB  - BACKGROUND: The diagnostic criteria for bronchiolitis obliterans syndrome (BOS)
      are predominantly adult-focused. The relationship between application and impact
      of reference equation choice on pediatric baseline lung function achieved and
      subsequent BOS diagnosis remains unclear. METHODS: Lung function spirometry data
      (FEV(1), FVC and FEF(25-75)) from pediatric subjects transplanted at the Great
      Ormond Street Hospital over a 10-year period were collated. Baseline values
      achieved after lung transplantation and BOS rates were examined. Raw values were
      compared with 2 different reference equations (the "Brompton" and modern collated
      "All-age" equations). The impact of FEF(25-75) baseline definition was
      investigated. RESULTS: Fifty subjects were included, 17 males and 33 females,
      transplanted at a median (range) age of 14.0 years (3.2 to 17.3 years, 83% >10
      years old), and followed for 1,028 (388 to 2,613) days post-transplantation. Raw
      values underestimated baseline lung function attainment for all indices.
      Magnitude of baseline lung function was affected by reference equation choice.
      Mean FEV(1) values were: Brompton 97.9% (SD 20.3%) and All-age 86.3% (SD 15.4%)
      of predicted (p < 0.0001). BOS 0p incidence was significantly higher for All-age
      predicted than for raw values (64% and 40%, respectively, p = 0.027).
      Modification of FEF(25-75) baseline (to either FEV(1) or FVC baseline) led to a
      reduction in BOS 0p detection (p < 0.01). CONCLUSIONS: Modern collated reference
      equations should be used for lung function monitoring in pediatric subjects after
      lung transplantation. Standardization of FEF(25-75) baseline definition is
      urgently required. These data question the utility of the FEF(25-75) criterion as
      an early marker of BOS 0p in pediatric subjects.

PMID- 25979625
TI  - MicroRNA-144 dysregulates the transforming growth factor-beta signaling cascade
      and contributes to the development of bronchiolitis obliterans syndrome after
      human lung transplantation.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS), chronic lung allograft
      rejection, remains an impediment for the function of the transplanted organ. In
      this study, we defined the role of the microRNA (miRNA) miR-144 in
      fibroproliferation leading to BOS. METHODS: Biopsy specimens were obtained from
      20 lung transplant recipients with BOS((+)) and 19 without BOS((-)). Expression
      of miR-144 and its target, transforming growth factor-beta (TGF-beta)-induced
      factor homeobox 1(TGIF1), were analyzed by real-time polymerase chain reaction
      and Western blot. Overexpression of miR-144 and luciferase reporter genes were
      performed to elucidate miRNA-target interactions. The function of miR-144 was
      evaluated by transfecting fibroblasts and determining the response to TGF-beta by
      analyzing Sma- and Mad-related family (Smads), fibroblast growth factor, TGF
      beta, and vascular endothelial growth factor. Smooth muscle actin-alpha-positive
      stress fibers and F-actin filaments in lung fibroblasts were analyzed by
      immunofluorescence. RESULTS: Analysis of miR-144 in the biopsy specimens
      demonstrated 4.1 +/- 0.8-fold increases in BOS(+) compared with BOS(-) patients,
      with a significant reduction in TGIF1 (3.6 +/- 1.2-fold), a corepressor of Smads.
      In vitro transfection confirmed that over-expression of miR-144 results in a
      reduction in TGIF1 and an increase in SMAD2, SMAD4, fibroblast growth factor-6,
      TGF-beta, and vascular endothelial growth factor. Increasing miR-144 by
      transfecting, increased smooth muscle actin-alpha and fibronectin, and knockdown
      of miR-144 diminished fibrogenesis in MRC-5 fibroblasts. CONCLUSIONS: miR-144 is
      a critical regulator of the TGF-beta signaling cascade and is over-expressed in
      lungs with BOS. Therefore, miR-144 is a potential target toward preventing
      fibrosis leading to BOS after lung transplant.

PMID- 25979627
TI  - 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-attenuates LPS/D-Gal
      induced acute hepatitis in mice.
AB  - The AMP-activated protein kinase (AMPK)-mediated energy-sensing signals play
      important roles in reprogramming the expression of inflammatory genes. In the
      present study, the potential effects of the AMPK activator 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR) were investigated in a mouse model
      with LPS/D-Gal-induced acute hepatitis. Our experimental data indicated that
      treatment with AICAR suppressed the elevation of plasma aminotransferases and
      alleviated the histopathological abnormalities in mice exposed to LPS/D-Gal.
      Treatment with AICAR also inhibited the LPS/D-Gal-induced up-regulation of TNF
      alpha, NO and myeloperoxidase. In addition, the LPS/D-Gal-induced expression of
      pro-apoptotic factor Bax, cleavage of caspase-3, elevation of hepatic caspase-3,
      caspase-8, caspase-9 activities and induction of terminal deoxynucleotidyl
      transferase-mediated nucleotide nick-end labeling-positive cells were all
      suppressed by AICAR. These results suggested that the AMPK activator AICAR could
      attenuate LPS/D-Gal-induced acute hepatitis, which implies that AMPK might become
      a novel target for the treatment of inflammation-based liver disorders.

PMID- 25979629
TI  - Validity and reliability in quantitative studies.

PMID- 25979628
TI  - Dysfunction of methionine sulfoxide reductases to repair damaged proteins by
      nickel nanoparticles.
AB  - BACKGROUND: Protein oxidation is considered to be one of the main causes of cell
      death, and methionine is one of the primary targets of reactive oxygen species
      (ROS). However, the mechanisms by which nickel nanoparticles (NiNPs) cause
      oxidative damage to proteins remain unclear. OBJECTIVES: The objective of this
      study is to investigate the effects of NiNPs on the methionine sulfoxide
      reductases (MSR) protein repairing system. METHODS: Two physically similar nickel
      based nanoparticles, NiNPs and carbon-coated NiNP (C-NiNPs; control particles),
      were exposed to human epithelial A549 cells. Cell viability, benzo(a)pyrene
      diolepoxide (BPDE) protein adducts, methionine oxidation, MSRA and B3,
      microtubule-associated protein 1A/1B-light chain 3 (LC3) and extracellular signal
      regulated kinase (ERK) phosphorylation were investigated. RESULTS: Exposure to
      NiNPs led to a dose-dependent reduction in cell viability and increased BPDE
      protein adduct production and methionine oxidation. The methionine repairing
      enzymatic MSRA and MSRB3 production were suppressed in response to NiNP exposure,
      suggesting the oxidation of methionine to MetO by NiNP was not reversed back to
      methionine. Additionally, LC3, an autophagy marker, was down-regulated by NiNPs.
      Both NiNP and C-NiNP caused ERK phosphorylation. LC3 was positively correlated
      with MSRA (r = 0.929, p < 0.05) and MSRB3 (r = 0.893, p < 0.05). CONCLUSIONS: MSR
      was made aberrant by NiNP, which could lead to the dysfunction of autophagy and
      ERK phosphorylation. The toxicological consequences may be dependent on the
      chemical characteristics of the nanoparticles.

PMID- 25979630
TI  - A third of Indian women who experience violence during pregnancy have
      complications.

PMID- 25979632
TI  - A new assessment method of posttraumatic psychiatric pathology.

PMID- 25979633
TI  - Winogradskyella eckloniae sp. nov., a marine bacterium isolated from the brown
      alga Ecklonia cava.
AB  - A novel bacterial strain, designated EC29(T), was isolated from the brown alga
      Ecklonia cava collected on Jeju Island, Republic of Korea. Cells of strain
      EC29(T) were Gram-stain-negative, aerobic, rod-shaped and motile by gliding.
      Growth was observed at 10-30  degrees C (optimum, 20-25  degrees C), at pH 6.0
      9.5 (optimum, pH 7.5) and in the presence of 1-5% (w/v) NaCl. Phylogenetic
      analyses based on the 16S rRNA gene sequence revealed that the strain belonged to
      the genus Winogradskyella. Strain EC29(T) exhibited the highest 16S rRNA gene
      sequence similarities, of 96.5-97.8%, to the type strains of Winogradskyella
      pulchriflava EM106(T), Winogradskyella echinorum KMM 6211(T) and Winogradskyella
      ulvae KMM 6390(T). Strain EC29(T) exhibited < 27% DNA-DNA relatedness with
      Winogradskyella pulchriflava EM106(T) and Winogradskyella echinorum KMM 6211(T).
      The predominant fatty acids of strain EC29(T) were iso-C15 : 0, iso-C15 : 1 G,
      C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and anteiso-C15 : 0. The DNA G+C
      content was 31.1 mol% and the major respiratory quinone was menaquinone-6 (MK-6).
      Based on a polyphasic study, strain EC29(T) is considered to represent a novel
      species of the genus Winogradskyella, for which the name Winogradskyella
      eckloniae sp. nov. is proposed. The type strain is EC29(T) ( = KCTC 32172(T) =
      JCM 18703(T)).

PMID- 25979634
TI  - A Psychophysiological Mechanism Underlying Women's Weight-Management Goals: Women
      Desire and Strive for Greater Weight Loss Near Peak Fertility.
AB  - Three studies demonstrated that conception risk was associated with increased
      motivations to manage weight. Consistent with the rationale that this association
      is due to ovulatory processes, Studies 2 and 3 demonstrated that it was moderated
      by hormonal contraceptive (HC) use. Consistent with the rationale that this
      interactive effect should emerge when modern appearance-related concerns
      regarding weight are salient, Study 3 used a 14-day diary to demonstrate that the
      interactive effects of conception risk and HC use on daily motivations to
      restrict eating were further moderated by daily motivations to manage body
      attractiveness. Finally, providing evidence that this interactive effect has
      implications for real behavior, daily fluctuations in the desire to restrict
      eating predicted daily changes in women's self-reported eating behavior. These
      findings may help reconcile prior inconsistencies regarding the implications of
      ovulatory processes by illustrating that such implications can depend on the
      salience of broader social norms. 

PMID- 25979631
TI  - Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis
      on germline CDH1 mutation carriers.
AB  - Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric
      (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised
      to discuss genetic testing, surgery, surveillance strategies, pathology reporting
      and the patient's perspective on multiple aspects, including diet post
      gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking
      into account first-degree and second-degree relatives): (1) families with two or
      more patients with gastric cancer at any age, one confirmed DGC; (2) individuals
      with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC
      (one diagnosis before the age of 50). Additionally, CDH1 testing could be
      considered in patients with bilateral or familial LBC before the age of 50,
      patients with DGC and cleft lip/palate, and those with precursor lesions for
      signet ring cell carcinoma. Given the high mortality associated with invasive
      disease, prophylactic total gastrectomy at a centre of expertise is advised for
      individuals with pathogenic CDH1 mutations. Breast cancer surveillance with
      annual breast MRI starting at age 30 for women with a CDH1 mutation is
      recommended. Standardised endoscopic surveillance in experienced centres is
      recommended for those opting not to have gastrectomy at the current time, those
      with CDH1 variants of uncertain significance and those that fulfil hereditary DGC
      criteria without germline CDH1 mutations. Expert histopathological confirmation
      of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy
      and mastectomy should not be underestimated; these can have severe consequences
      on a psychological, physiological and metabolic level. Nutritional problems
      should be carefully monitored. 

PMID- 25979635
TI  - Experiences of Uncertainty in Men With an Elevated PSA.
AB  - A significant proportion of men, ages 50 to 70 years, have, and continue to
      receive prostate specific antigen (PSA) tests to screen for prostate cancer
      (PCa). Approximately 70% of men with an elevated PSA level will not subsequently
      be diagnosed with PCa. Semistructured interviews were conducted with 13 men with
      an elevated PSA level who had not been diagnosed with PCa. Uncertainty was
      prominent in men's reactions to the PSA results, stemming from unanswered
      questions about the PSA test, PCa risk, and confusion about their management
      plan. Uncertainty was exacerbated or reduced depending on whether health care
      providers communicated in lay and empathetic ways, and provided opportunities for
      question asking. To manage uncertainty, men engaged in information and health
      care seeking, self-monitoring, and defensive cognition. Results inform strategies
      for meeting informational needs of men with an elevated PSA and confirm the
      primary importance of physician communication behavior for open information
      exchange and uncertainty reduction.

PMID- 25979636
TI  - Vagus nerve stimulation therapy is effective and safe for startle-induced
      seizures.

PMID- 25979637
TI  - Executive dysfunction in patients with transient ischemic attack and minor
      stroke.
AB  - BACKGROUND AND OBJECTIVE: A considerable number of patients with transient
      ischemic attack suffer from cognitive impairment, even after recovery of focal
      neurological deficits. In particular, executive functions such as working memory,
      abstraction, reasoning, verbal fluency and cognitive flexibility are impaired in
      these patients. The purpose of the present study was to explore the nature and
      prevalence of cognitive impairment in a series of patients with transient
      ischemic attack and minor stroke. MATERIALS AND METHODS: We included 140 patients
      (61% women) who presented with a focal cerebral ischemic event lasting less than
      24h in the Urgent TIA outpatient clinic. All patients underwent a brief battery
      of neuropsychological tests, consisting of the Mini Mental State Examination
      (MMSE), Neurobehavioral Cognitive Status Examination-Judgment Subtest, Clock
      Drawing Test and Trail Making Test. RESULTS: A majority of patients (57%) were
      impaired on one or more of these neuropsychological tests. Nearly one-third of
      individuals were impaired on two or more tests. Cognitive impairment was most
      frequently observed on the Trail Making Test Part A (31% of patients) and Part B
      (40%). The Trail Making Test examines executive functions, as it requires
      cognitive flexibility, ability to maintain a complex response set and speed of
      processing. By contrast, only 5% of patients were impaired on the MMSE, a widely
      used neuropsychological test insensitive to executive dysfunction. CONCLUSIONS:
      Our results highlight the limitations of the MMSE as an independent cognitive
      screening instrument for patients with TIAs and minor stroke and the high
      prevalence of executive dysfunction in these patients.

PMID- 25979638
TI  - Prior in vitro exposure to voriconazole confers resistance to amphotericin B in
      Aspergillus fumigatus biofilms.
AB  - Triazoles are the mainstay of treatment for aspergillosis, although resistance to
      these antifungal agents may be associated with treatment failure. Refractory
      infections often necessitate a switch to other antifungal agents, including
      amphotericin B (AmB), although these infections may not resolve. The aim of this
      study was to investigate the effect of prior azole exposure on AmB sensitivity in
      Aspergillus fumigatus biofilms. It was hypothesised that sequential antifungal
      therapy has the potential to impact adaptive resistance mechanisms. Antifungal
      sensitivity was determined for each isolate against AmB+/-voriconazole (VRZ)
      exposure by a broth microdilution method and an XTT metabolic assay. To analyse
      the role of extracellular DNA (eDNA) and Hsp90 activation, sensitivity to AmB+/
      DNA-digesting enzyme (DNase) or Hsp90 inhibitor [geldanamycin (GDA)] was also
      tested. Finally, scanning electron microscopy was performed to assess phenotypic
      changes. The in vitro data revealed that A. fumigatus sensitivity to AmB was
      decreased when it was tested in combination with VRZ. In addition, a two- to four
      fold decreased sensitivity to AmB was recorded against VRZ-exposed germlings
      compared with controls. It was also shown that depletion of eDNA by DNase
      treatment enhanced AmB activity against VRZ-exposed cells by eight-fold, which
      visually could be explained by destabilisation of the biofilm when examined
      microscopically. Pharmacological inhibition of Hsp90 by GDA significantly
      improved biofilm susceptibility to AmB by four- to eight-fold. In conclusion, A.
      fumigatus pre-exposure to VRZ concomitantly induces eDNA release and activates
      the stress response, which collectively confers AmB resistance in vitro. 

PMID- 25979639
TI  - Ecological effect of ceftazidime/avibactam on the normal human intestinal
      microbiota.
AB  - Ceftazidime/avibactam is a new combination of the antibiotic ceftazidime with the
      novel, non-beta-lactam beta-lactamase inhibitor avibactam. The purpose of the
      present study was to investigate the effect of ceftazidime/avibactam on the human
      intestinal microbiota following intravenous (i.v.) administration. Twelve healthy
      volunteers received ceftazidime/avibactam by i.v. infusion (2000mg ceftazidime
      and 500mg avibactam) given over 2h every 8h on Days 1-6 (inclusive) and a single
      dose on Day 7. Faecal samples were collected on Day-1 (pre-dose), during
      administration on Days 2, 5 and 7 and post-dose on Days 9, 14 and 21. Samples
      were cultured on non-selective and selective media. The number of Escherichia
      coli and other enterobacteria decreased significantly during administration of
      ceftazidime/avibactam, whereas the number of enterococci increased. Lactobacilli,
      bifidobacteria, clostridia and Bacteroides decreased significantly during
      ceftazidime/avibactam administration. The effects on lactobacilli, bifidobacteria
      and Bacteroides were similar in the 12 volunteers, whilst clostridia showed
      different ecological patterns among the volunteers. Toxigenic Clostridium
      difficile strains were detected in five volunteers during the study. In four of
      the volunteers, loose stools were reported as adverse events. Plasma samples were
      collected on Days -1, 2, 5 and 7. Ceftazidime and avibactam concentrations in
      plasma (ceftazidime 0-224.2mg/L of plasma and avibactam 0-70.5mg/L of plasma) and
      faeces (ceftazidime 0-468.2mg/kg of faeces and avibactam 0-146.0mg/kg of faeces)
      were found by bioassay. New colonising resistant clostridia were found in five
      volunteers and lactobacilli were found in three volunteers. 

PMID- 25979641
TI  - Remarkable Pathologic Change in Advanced Prostate Cancer Patient Using Dendritic
      Cell-Cytokine-Induced Killer Combined Therapy: A Case Report.

PMID- 25979640
TI  - Forecasting carbapenem resistance from antimicrobial consumption surveillance:
      Lessons learnt from an OXA-48-producing Klebsiella pneumoniae outbreak in a West
      London renal unit.
AB  - This study aimed to forecast the incidence rate of carbapenem resistance and to
      assess the impact of an antimicrobial stewardship intervention using routine
      antimicrobial consumption surveillance data. Following an outbreak of OXA-48
      producing Klebsiella pneumoniae (January 2008-April 2010) in a renal cohort in
      London, a forecasting ARIMA model was derived using meropenem consumption data
      [defined daily dose per 100 occupied bed-days (DDD/100OBD)] from 2005-2014 as a
      predictor of the incidence rate of OXA-48-producing organisms (number of new
      cases/year/100,000OBD). Interrupted times series assessed the impact of meropenem
      consumption restriction as part of the outbreak control. Meropenem consumption at
      lag -1 year (the preceding year), highly correlated with the incidence of OXA-48
      producing organisms (r=0.71; P=0.005), was included as a predictor within the
      forecasting model. The number of cases/100,000OBD for 2014-2015 was estimated to
      be 4.96 (95% CI 2.53-7.39). Analysis of meropenem consumption pre- and post
      intervention demonstrated an increase of 7.12 DDD/100OBD/year (95% CI 2.97-11.27;
      P<0.001) in the 4 years preceding the intervention, but a decrease thereafter.
      The change in slope was -9.11 DDD/100OBD/year (95% CI -13.82 to -4.39). Analysis
      of alternative antimicrobials showed a significant increase in amikacin
      consumption post-intervention from 0.54 to 3.41 DDD/100OBD/year (slope +0.72, 95%
      CI 0.29-1.15; P=0.01). Total antimicrobials significantly decreased from 176.21
      to 126.24 DDD/100OBD/year (P=0.05). Surveillance of routinely collected
      antimicrobial consumption data may provide a key warning indicator to anticipate
      increased incidence of carbapenem-resistant organisms. Further validation using
      real-time data is needed. 

PMID- 25979642
TI  - Acute and repeated doses (28 days) oral toxicity study of glycosides based
      standardized fenugreek seed extract in laboratory mice.
AB  - The objective of the present work was to study acute and subacute (28-days
      repeated dose) oral toxicity effect of glycosides based standardized fenugreek
      seed extract (SFSE-G) in vivo. SFSE-G was prepared by resin-based chromatography
      and standardized to glycosides namely trigoneoside Ib (76%) and vicenin 1 (15%).
      The acute oral toxicity (AOT) and subacute toxicity studies were performed in
      Swiss albino mice (5 mice/sex/group) as per OECD 425 (up-and-down procedure) and
      OCED 407 guidelines respectively. Acute oral administration of 5000mg/kg of SFSE
      G showed 40% mortality with no mortality in lower dosages. The subacute oral
      administration of SFSE-G did not show observational or toxicological effects on
      the body or organ weights, food consumption, ophthalmic effects, locomotor
      activity, hematology, blood biochemistry, urinalysis, or histopathology at dose
      250mg/kg. However, SFSE-G (1000mg/kg) showed mortality and minor alterations to
      body weight, relative liver weights, hematology and blood chemistry parameters
      related to treatment but it was within normal laboratory ranges. In conclusion,
      SFSE-G showed median lethal dose (LD50) more than 4350mg/kg and no-observed
      adverse effect levels (NOAEL) of 250mg/kg for both sexes during AOT and sub-acute
      toxicity study, respectively. 

PMID- 25979643
TI  - Nanoparticles skin absorption: New aspects for a safety profile evaluation.
AB  - Nanoparticles (NPs) skin absorption is a wide issue, which needs to be better
      understood. The attempt of this review is to summarize the scientific evidence
      concerning open questions, i.e.: the role of NPs intrinsic characteristics (size,
      shape, charge, surface properties), the penetration of NPs through the intact or
      impaired skin barrier, the penetration pathways which should be considered and
      the role of NPs interaction in physiological media. The outcomes suggest that one
      main difference should be made between metal and non-metal NPs. Both kinds have a
      secondary NPs size which is given after interaction in physiological media, and
      allows a size-dependent skin penetration: NPs?4nm can penetrate and permeate
      intact skin, NPs size between 4 and 20nm can potentially permeate intact and
      damaged skin, NPs size between 21 and 45nm can penetrate and permeate only
      damaged skin, NPs size>45nm cannot penetrate nor permeate the skin. Other aspects
      play an important role, mostly for metal NPs, i.e., dissolution in physiological
      media, which can cause local and systemic effects, the sensitizing or toxic
      potential and the tendency to create aggregates. This paper suggests a decision
      tree to evaluate the potential risk for consumers and workers exposed to NPs. 

PMID- 25979644
TI  - A reexamination of medical marijuana policies in relation to suicide risk.
AB  - OBJECTIVES: Previous research has suggested that medical marijuana policies lead
      to reductions in suicide rates. In this study, we further investigate the
      association between these policies and within-state changes in suicide risk.
      METHODS: Data on suicide deaths (n=662,993) from the National Vital Statistics
      System Multiple Cause of Death files were combined with living population data.
      Fixed-effects regression methods were employed to control for state differences
      in suicide rates and national and state secular trends. Analyses extended prior
      research that suggested a protective effect of medical marijuana policies by
      incorporating newer data and additional covariates. RESULTS: After adjustment for
      race/ethnicity, tobacco control policies, and other covariates, we found no
      association between medical marijuana policy and suicide risk in the population
      ages 15 and older (OR=1.000; 95% CI: 0.956, 1.045; p=0.98), among men overall
      (OR=0.996; 95% CI: 0.951, 1.043; p=0.87) or for any other age-by-sex groups.
      CONCLUSION: We find no statistically significant association between medical
      marijuana policy and suicide risk. These results contradict prior analyses which
      did not control for race/ethnicity and certain state characteristics such as
      tobacco control policies. Failure to control for these factors in future analyses
      would likely bias estimates of the associations between medical marijuana policy
      and health outcomes.

PMID- 25979646
TI  - Defining the High-Risk Population for Mortality After Resection of Early Stage
      NSCLC.
AB  - The National Cancer Data Base was examined for predictors of 30-day mortality (30
      DM) in early stage none small-cell lung cancer patients undergoing resection. The
      rate of 30-DM was 2.2%. Age, community treatment center, male sex, and Charlson
      Deyo comorbidity score were predictive of higher mortality. Extent of resection
      was predictive of higher 30-DM in patients aged ? 75 years. BACKGROUND: Studies
      examining morbidity after lobectomy for early stage non-small-cell lung cancer
      (NSCLC) demonstrate a > 50% incidence of complications in patients aged >= 65
      years. Factors that affect 30-day mortality (30-DM), however, are less well
      defined. MATERIALS AND METHODS: The National Cancer Data Base was used to
      identify patients age >= 19 years with stage I NSCLC between 2003 and 2011. Data
      from patients undergoing lobectomy or sublobar resection was abstracted.
      Univariable and multivariable logistic regression analyses were performed for
      predictors of 30-DM. RESULTS: A total of 71,175 patients met inclusion criteria.
      Of these, 81% underwent lobectomy and 19% underwent sublobar resection. The
      median age was 68 years. Charlson-Deyo (CD) comorbidity score was 0 in 49% of
      patients and 1 or higher in 51%. The rate of 30-DM was 2.2%. On multivariable
      analysis, younger age, CD score of 0, female sex, tumor size <= 3 cm, and
      treatment at an academic center was associated with lower 30-DM (P < .001). A
      model of 30-DM incorporating age, comorbidity, and extent of surgery was created.
      In patients aged < 75 years without comorbidities, 30-DM was 1.3%. However, in
      elderly patients (>= 75 years old) with CD score of 2, this rate quadrupled to
      5.8% (P < .01). Lobectomy patients in this group had higher 30-DM compared to
      sublobar resection patients (6.6% vs. 3.9% respectively, P < .01). CONCLUSION:
      The 30-DM rate following sublobar or lobar resection in this national sample was
      low. Extent of resection appears to influence 30-DM in the elderly. Elderly
      patients with a CD score of 2 undergoing lobectomy represent a high-risk group
      for 30-DM.

PMID- 25979645
TI  - Clozapine reconstructed: Haloperidol's ability to reduce alcohol intake in the
      Syrian golden hamster can be enhanced through noradrenergic modulation by
      desipramine and idazoxan.
AB  - BACKGROUND: Alcohol use disorder commonly occurs in patients with schizophrenia.
      Most antipsychotic drugs do not lessen alcohol use; although the atypical
      antipsychotic clozapine has been shown to reduce alcohol use in patients with
      schizophrenia, its toxicity severely limits its use in patients. With an eye
      toward creation of a safer clozapine-like drug, we have investigated the
      pharmacological basis of the clozapine's effects on alcohol drinking in the
      Syrian golden hamster. In this animal, as in patients with schizophrenia,
      clozapine reduces alcohol drinking while the typical antipsychotic haloperidol
      does not. We have suggested that clozapine decreases alcohol drinking due to its
      weak dopamine D2 receptor blockade, its potent norepinephrine alpha-2 receptor
      antagonism, as well as its ability to elevate plasma norepinephrine. METHODS: We
      recreated a clozapine-like drug to reduce alcohol drinking in the Syrian golden
      hamster by combining low dose haloperidol with a norepinephrine alpha-2 receptor
      antagonist, idazoxan, and a norepinephrine reuptake inhibitor, desipramine.
      Hamsters were given free access to water and alcohol (15% v/v) and were treated
      daily with each drug or with the three-drug combination for 23 days. RESULTS: The
      drug combination reduced alcohol drinking and preference significantly as
      compared to vehicle or to haloperidol, idazoxan or desipramine, while not
      altering food-intake or body-weight. CONCLUSION: These findings suggest that that
      haloperidol, which does not reduce alcohol drinking in patients with
      schizophrenia or the hamster, if combined with idazoxan and desipramine
      (producing a drug combination that mimics aspects of clozapine's pharmacology) is
      able to reduce alcohol drinking in the hamster.

PMID- 25979647
TI  - Autophagy Inhibition Overcomes the Antagonistic Effect Between Gefitinib and
      Cisplatin in Epidermal Growth Factor Receptor Mutant Non--Small-Cell Lung Cancer
      Cells.
AB  - BACKGROUND: Four large clinical trials have shown that concurrent administration
      of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI),
      such as gefitinib or erlotinib, with chemotherapy agents does not improve overall
      survival (OS) in unselected patients with advanced non-small-cell lung cancer
      (NSCLC). In the present study, the role of autophagy in the combination of
      gefitinib and cisplatin on EGFR-TKI-sensitive human lung cancer cell line was
      investigated. Moreover, whether simultaneous autophagy inhibition treatment
      increases the antitumor activity was explored. MATERIALS AND METHODS: The PC9
      cell was exposed to either gefitinib or cisplatin alone or together. Cell
      viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The cytotoxic interaction between gefitinib
      and cisplatin was determined using coefficient of drug interaction (CDI)
      analysis. The cell cycle distribution and apoptosis were measured using flow
      cytometry. Alterations in the autophagy and apoptosis signaling pathway were
      measured using Western blot assays. RESULTS: Coadministration of gefitinib and
      cisplatin resulted in antagonistic activity to tumor cell proliferation. However,
      the addition of chloroquine (CQ), an autophagy inhibitor, overcame the
      antagonistic effects, as demonstrated by CDI analysis and Annexin V
      FITC/propidium iodide (PI) assays. In addition, gefitinib administration led to
      cell G1 phase arrest, which might have contributed to the antagonistic activity
      between gefitinib and cisplatin. However, the addition of CQ did not deregulate
      cell cycle arrest, indicating that other mechanisms might be involved. The
      Annexin V-FITC/PI assays showed that the addition of CQ significantly the
      increased the ratio of apoptosis cells. Also, immunoblotting assays exhibited
      increased Bax and decreased Bcl-2, suggesting that autophagy inhibition by CQ
      could increase cell apoptosis and thus overcome the antagonistic effects.
      CONCLUSION: The combination of gefitinib with cisplatin generates antagonistic
      effects on EGFR-TKI-sensitive cells. However, inhibiting autophagy produces a
      synergistic effect, suggesting that gefitinib and cisplatin combined with an
      autophagy inhibitor (especially CQ) might be a beneficial strategy to overcome
      the antagonistic effects between EGFR-TKIs and chemotherapeutic agents.

PMID- 25979648
TI  - delta-Tocotrienol treatment is more effective against hypoxic tumor cells than
      normoxic cells: potential implications for cancer therapy.
AB  - Tocotrienols, unsaturated forms of vitamin E, inhibit the proliferation of a
      variety of cancer cells and suppress angiogenesis. However, the mechanisms
      underlying those effects on cancer cell growth remain unclear especially under
      hypoxic conditions. In this study, we demonstrated that delta-tocotrienol (delta
      T3) could be used as a novel anticancer agent against human colorectal
      adenocarcinoma (DLD-1) cells under both normoxic and hypoxic conditions. delta-T3
      inhibited the growth of DLD-1 cells in a dose-dependent fashion by inducing cell
      cycle arrest and apoptosis. This effect was more potent under hypoxic than
      normoxic conditions. The anticancer effect of delta-T3 was achieved by its up
      regulation of cyclin-dependent kinase inhibitors (p21 and p27), the activation of
      caspases and the suppression of phosphorylation of protein kinase B (Akt) at
      Thr(308) and Ser(473). In in vivo studies, oral administration of rice bran
      tocotrienol (RBT3, mainly gamma-T3) (10 mg/mouse/day) significantly inhibited
      tumor growth in nude mice. In tumor analyses, RBT3 activated p21, p27, caspase-3
      and caspase-9 and decreased Akt phosphorylation. Furthermore, immunostaining
      revealed that RBT3 decreased the number of cells positive for CD31/platelet
      endothelial cell adhesion molecule-1 in microvessels in the tumor. Taken
      together, these data suggest that tocotrienols are potent antitumor agents
      capable of inducing apoptosis and inhibiting angiogenesis under both hypoxic and
      normoxic conditions. Tocotrienols could have significant therapeutic potential in
      the clinical treatment of tumors. 

PMID- 25979649
TI  - Application of intraoperative magnetic resonance imaging in large invasive
      pituitary adenoma surgery.
AB  - OBJECTIVE: To investigate the clinical application value of intraoperative
      magnetic resonance imaging (iMRI) in large invasive pituitary adenoma surgery.
      METHODS: A total of 30 patients with large pituitary adenoma underwent
      microscopic tumor resection under the assistance of an iMRI system; 26 cases
      received surgery through the nasal-transsphenoidal approach, and the remaining
      four cases received surgery through the pterion approach. iMRI was performed one
      or two times depending on the need of the surgeon. If a residual tumor was found,
      further resection was conducted under iMRI guidance. RESULTS: iMRI revealed
      residual tumors in 12 cases, among which nine cases received further resection.
      Of these nine cases, iMRI rescanning confirmed complete resection in six cases,
      and subtotal resection in the remaining three. Overall, 24 cases of tumor were
      totally resected, and six cases were subtotally resected. The total resection
      rate of tumors increased from 60% to 80%. CONCLUSION: iMRI can effectively
      determine the resection extent of pituitary adenomas. In addition, it provides an
      objective basis for real-time judgment of surgical outcome, subsequently
      improving surgical accuracy and safety, and increasing the total tumor resection
      rate.

PMID- 25979650
TI  - Expression of cell cycle regulators, 14-3-3sigma and p53 proteins, and vimentin
      in canine transitional cell carcinoma of the urinary bladder.
AB  - OBJECTIVES: The study of the expression of 14-3-3sigma, p53, and vimentin
      proteins in canine transitional cell carcinoma (TCC) evaluating differences with
      normal bladder tissues, and the association with clinicopathological variables.
      METHODS: We analyze by immunohistochemistry in 19 canine TCCs the expression of
      14-3-3sigma, p53, and vimentin using monoclonal antibodys. A semiquantitative
      scoring method was employed and statistical analysis was performed to display
      relationships between variables. RESULTS: In contrast to normal urinary bladder
      epithelium, which showed high levels of 14-3-3sigma, its expression was decreased
      in 53% of the studied tumors (P = 0.0344). The 14-3-3sigma protein was expressed
      by neoplastic emboli and by highly infiltrative neoplastic cells. The p53 protein
      was expressed in 26% of TCCs, but no significant association between 14-3-3sigma
      and p53 was detected. Neoplastic epithelial cells displayed vimentin
      immunoreactivity in 21% of TCCs, and a positive correlation with mitotic index
      was observed (P = 0.042). Coexpression of vimentin and 14-3-3sigma by highly
      infiltrative neoplastic cells was also observed. CONCLUSIONS: 14-3-3sigma is
      deregulated in canine TCCs and its expression by highly infiltrative tumor cells
      may be related to the acquisition of aggressive behavior. Furthermore, this
      article reinforce the role of canine TCC as relevant model of human urothelial
      carcinoma and we suggest 14-3-3sigma as a potential therapeutic target. Further
      studies are necessary to clarify the role of 14-3-3sigma in canine TCC.

PMID- 25979651
TI  - Small renal masses in the era of personalized medicine: Tumor heterogeneity,
      growth kinetics, and risk of metastasis.
AB  - Small renal masses (SRMs) represent a heterogeneous group showing a variety of
      clinical and biological behaviors. The best treatment for SRMs has been the focus
      of much debate over the past decades. Present strategies include surgery (partial
      or radical nephrectomy), local treatments (radiofrequency and cryoablation), or
      active surveillance. The choice among these therapeutic options is based on
      patient clinical features such as age or comorbidities rather than on tumor
      characteristics. Several studies have recently focused on the molecular behavior
      of SRMs. They showed that SRMs present histotype and nuclear grading
      heterogeneity, together with not unvarying growth kinetics and risk of recurrence
      or metastasis, suggesting that personalized approaches should be designed to
      optimize the management of these patients. At present, several studies are in
      course to identify predictive biomarkers to guide the decision-making process in
      this subpopulation. In this review, we summarized the data on growth kinetics,
      tumor heterogeneity, and risk of metastasis in patients with SRMs, with focus on
      the current role of biopsies and imaging in the management of these patients. 

PMID- 25979652
TI  - Tonsillectomy, adenoidectomy and adenotonsillectomy rates in school-aged
      children: Relative contributions of socio-demographic and clinical features.
AB  - OBJECTIVES: The present study sought to investigate the frequencies of
      tonsillectomy, adenoidectomy and both adenotonsillectomy (T&A) among 6-12 years
      old children. In addition, we tried to find out the predictors associated with
      these previous upper respiratory tract (URT) surgeries. METHODS: This cross
      sectional study consisted of 1900 children educated in 3 different elementary
      schools in Ankara, Turkey. Data about demographics and health conditions were
      obtained from survey questionnaires completed by parents. RESULTS: Of the 1900
      children, 15 children (0.8%) previously underwent tonsillectomy, 43 children
      (2.3%) had adenoidectomy and 80 children (4.2%) had T&A surgical histories.
      Multiple logistic regression analysis revealed that older students compared to
      younger ones [odds ratio (OR) = 1.15, p = 0.011], and those who had parent
      reported apnea compared to subjects without apnea were more likely to have URT
      surgery histories [OR = 2.34, p = 0.001]. Those children with surgery histories
      were more likely to have fathers with a higher educational level [medium level:
      OR = 2.07, p = 0.012; high level: OR = 2.79, p = 0.001 vs. low level) and the
      subjects had greater BMI percentiles [overweight: OR = 1.71, p = 0.036; obesity:
      OR = 2.32, p = 0.003 vs. healthy weight]. Children who had 1-2 URT infections per
      year [OR = 0.47, p = 0.019] had less probability of URT surgery histories,
      whereas those children with AOM >= 3 times per year [OR = 2.52, p = 0.003] had
      more probability of URT surgery history. CONCLUSIONS: We conclude that a
      reasonable explanation for higher rates of URT surgery among children with a high
      level of paternal education may originate from their awareness about URT
      associated diseases and possibly due to the ease of access to health care
      services.

PMID- 25979653
TI  - Severe Chronic Upper Airway Disease (SCUAD) in children. Definition issues and
      requirements.
AB  - OBJECTIVES: Upper airway diseases are extremely common, and a significant
      proportion of patients are not adequately controlled by contemporary treatment
      algorithms. The term SCUAD (Severe Chronic Upper Airway Disease) has been
      previously introduced to describe such cases. However, this term has not been
      adequately focused on children. METHODS: This study aims to address the necessity
      of the term, as well as further details specifically for children. For this
      purpose, a review was performed of the current literature, with specific focus on
      issues regarding SCUAD in children. RESULTS: Paediatric SCUAD represents a
      heterogeneous group of patients and has significant clinical and socioeconomic
      implications. Relevant literature is generally lacking and questions regarding
      definition and pathogenesis remain unanswered. CONCLUSIONS: Accurate definition
      and acknowledgement of paediatric SCUAD cases may lead to better design of future
      clinical and molecular research protocols. This may provide improved
      understanding of the underlying disease processes, more accurate data regarding
      socioeconomic burden, and, above all, more successful treatment and prevention
      strategies.

PMID- 25979655
TI  - Factor H-related proteins determine complement-activating surfaces.
AB  - Complement factor H-related proteins (FHRs) are strongly associated with
      different diseases involving complement dysregulation, which suggests a major
      role for these proteins regulating complement activation. Because FHRs are
      evolutionarily and structurally related to complement inhibitor factor H (FH),
      the initial assumption was that the FHRs are also negative complement regulators.
      Whereas weak complement inhibiting activities were originally reported for these
      molecules, recent developments indicate that FHRs may enhance complement
      activation, with important implications for the role of these proteins in health
      and disease. We review these findings here, and propose that FHRs represent a
      complex set of surface recognition molecules that, by competing with FH, provide
      improved discrimination of self and non-self surfaces and play a central role in
      determining appropriate activation of the complement pathway. 

PMID- 25979654
TI  - Indoctrinating T cells to attack pathogens through homeschooling.
AB  - Adaptive immunity is predicated on the ability of the T cell repertoire to have
      pre-existing specificity for the universe of potential pathogens. Recent findings
      suggest that T cell receptor (TCR)-self-major histocompatibility protein (pMHC)
      interactions limit autoimmune responses while enhancing T cell response to
      foreign antigens. We review these findings here, placing them in context of the
      current understanding of how TCR-self-pMHC interactions regulate T cell
      activation thresholds, and suggest that TCR-self-pMHC interactions increase the
      efficiency of the T cell repertoire by giving a competitive advantage to peptide
      cross-reactive T cells. We propose that self-reactivity and peptide cross
      reactivity are controlled by particular CDR3 sequence motifs, which would allow
      thymic selection to contribute to solving the feat of broad pathogen specificity
      by exporting T cells that are pre-screened by positive and negative selection for
      the ability to be 'moderately' peptide cross-reactive. 

PMID- 25979656
TI  - Lengthened superstimulatory treatment in cattle: Evidence for rescue of follicles
      within a wave rather than continuous recruitment of new follicles.
AB  - A study was designed to compare the effects of a conventional (4 days) versus a
      lengthened (7 days) superstimulation protocol on follicle dynamics and to test
      the hypothesis that superstimulatory treatment only rescues small follicles
      within the wave. Nonlactating beef cows received a progesterone-releasing
      intravaginal device [PRID] and were superstimulated with 400-mg FSH on the day of
      follicle ablation-induced wave emergence (Day 0). The control group (n = 5)
      received FSH over 4 days, whereas the long group (n = 5) received FSH over 7
      days. PGF was administered twice on Day 2 (control group) or 5 (long group), and
      PRIDs were removed 24 hours after the first PGF. Cows received 25-mg LH 24 hours
      after PRID removal. The cows chosen for the present study represented a subset
      from a larger group of 24 cows in which superovulation results were obtained and
      published. Cows in the present study were those with the lowest antral follicle
      counts at the time of wave emergence in order to facilitate tracking of
      individual follicles. Daily ultrasonographic examinations monitored follicle
      diameters and numbers. A reduction (P < 0.01) in the number of 1- to 2-mm
      follicles from Day 0 to the end of the superstimulatory treatment was associated
      with a progressive shift to the next size category in both groups. On the day of
      LH treatment, the number of follicles in any size category did not differ between
      groups. The number of follicles of diameter 5 mm or less decreased during
      superstimulation (i.e., no continuous recruitment of small follicles; P < 0.001),
      and the number of follicles of diameter 1 mm or greater at the end of
      superstimulation did not differ from that at the beginning of superstimulation (P
      = 0.739). However, the total number of follicles of diameter 3 mm or greater at
      the end was greater than the number of follicles of diameter 3 mm or greater at
      the beginning of superstimulation because of growth of the 1- to 2-mm population
      during treatment (P < 0.001). Follicle growth was slower in the long group than
      in the control group. Results support the hypothesis that both 4-day and 7-day
      superstimulatory protocols rescue small antral follicles present at the time of
      wave emergence; there was no evidence for continuous recruitment of new
      follicles. Results also provide rationale for the hypothesis that a lengthened
      treatment protocol is associated with greater follicle maturation and capacity to
      ovulate.

PMID- 25979657
TI  - Effect of different gonadorelin (GnRH) products used for the first or
      resynchronized timed artificial insemination on pregnancy rates in postpartum
      dairy cows.
AB  - Different GnRH products are used for timed artificial insemination (AI) in
      postpartum dairy cows. Previous studies reported greater LH release and increased
      ovulation percentage for gonadorelin diacetate tetrahydrate compared with
      gonadorelin hydrochloride but pregnancies per AI (P/AI) were not evaluated. The
      objective, therefore, was to compare P/AI for cows treated with either
      gonadorelin hydrochloride or gonadorelin diacetate tetrahydrate before the first
      timed AI or resynchronized timed AI. Holstein cows (n = 3938) in a confinement
      dairy in northeast Missouri were assigned to weekly cohorts (n = 22) on the basis
      of calving date. Cows were treated with "Presynch Ovsynch" (PGF2alpha, 14 days;
      PGF2alpha, 14 days; GnRH, 7 days; PGF2alpha, 56 hours; GnRH, 16 hours; timed AI)
      so that the first timed AI was 70 to 76 days postpartum. The PGF2alpha was
      Lutalyse (5 mL; 25 mg; Zoetis). The GnRH product was either gonadorelin
      hydrochloride (2 mL; 100 MUg; n = 1945) or gonadorelin diacetate tetrahydrate (2
      mL; 100 MUg; n = 1993) and alternated weekly for cows assigned to cohorts. There
      were first timed AI (n = 1790) and resynchronized timed AI (n = 2148) cows within
      each cohort. The resynchronization began 32 days after timed AI (GnRH, 6 days;
      ultrasound pregnancy diagnosis, 1 day; and then for nonpregnant cows: PGF2alpha,
      56 hours; GnRH, 16 hours; timed AI). The trial was conducted from January to
      February 2012 (n = 1203) and July to October 2012 (n = 2735). Cows were fed a
      total mixed ration, milked thrice daily, and milk tested monthly for volume,
      somatic cell count (SCC), fat percentage, protein percentage, and milk urea
      nitrogen. Data were analyzed by fitting the binary response data to a generalized
      linear mixed model for repeated measures. There was no effect of the GnRH product
      (treatment) on P/AI (38.4 +/- 1.2 vs. 35.7 +/- 1.3; gonadorelin diacetate
      tetrahydrate vs. gonadorelin hydrochloride). Treatment interactions with parity,
      month of breeding, or insemination number were not significant. The first-service
      P/AI (38.8 +/- 1.4%) was greater (P < 0.05) than the resynchronized P/AI (35.3 +/
      1.3%). Cows inseminated in the summer had lesser P/AI (effect of month; P <
      0.001) compared with cows inseminated in the winter. There was a decrease (P <
      0.002) in timed AI conception for cows with a greater milk SCC and an increase (P
      < 0.003) in P/AI for cows with a greater milk protein percentage. In conclusion,
      the GnRH product did not affect P/AI for the first or resynchronized timed AI in
      an Ovsynch-based program. Other factors affected P/AI including service number
      (lesser for the second service or greater), month (lesser in summer months), SCC
      (lesser for cows with greater SCC), and milk protein percentage (greater for cows
      with greater protein percentage). 

PMID- 25979658
TI  - Lung endothelial barrier protection by resveratrol involves inhibition of HMGB1
      release and HMGB1-induced mitochondrial oxidative damage via an Nrf2-dependent
      mechanism.
AB  - High-mobility group box 1 (HMGB1) contributes to lung vascular hyperpermeability
      during ventilator-induced lung injury. We aimed to determine whether the natural
      antioxidant resveratrol protected against HMGB1-induced endothelial
      hyperpermeability both in vitro and in vivo. We found that HMGB1 decreased
      vascular endothelial (VE)-cadherin expression and increased endothelial
      permeability, leading to mitochondrial oxidative damage in primary cultured mouse
      lung vascular endothelial cells (MLVECs). Both the mitochondrial superoxide
      dismutase 2 mimetic MnTBAP and resveratrol blocked HMGB1-induced mitochondrial
      oxidative damage, VE-cadherin downregulation, and endothelial hyperpermeability.
      In in vivo studies, anesthetized male ICR mice were ventilated for 4h using low
      tidal volume (6 ml/kg) or high tidal volume (HVT; 30 ml/kg) ventilation. The mice
      were injected intraperitoneally with resveratrol immediately before the onset of
      ventilation. We found that resveratrol attenuated HVT-associated lung vascular
      hyperpermeability and HMGB1 production. HVT caused a significant increase in
      nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and Nrf2
      target gene expression in lung tissues, which was further enhanced by resveratrol
      treatment. HMGB1 had no effect on Nrf2 activation, whereas resveratrol treatment
      activated the Nrf2 signaling pathway in HMGB1-treated MLVECs. Moreover, Nrf2
      knockdown reversed the inhibitory effects of resveratrol on HMGB1-induced
      mitochondrial oxidative damage and endothelial hyperpermeability. The inhibitory
      effect of resveratrol on cyclic stretch-induced HMGB1 mRNA expression in primary
      cultured MLVECs was also abolished by Nrf2 knockdown. In summary, this study
      demonstrates that resveratrol protects against lung endothelial barrier
      dysfunction initiated by HVT. Lung endothelial barrier protection by resveratrol
      involves inhibition of mechanical stretch-induced HMGB1 release and HMGB1-induced
      mitochondrial oxidative damage. These protective effects of resveratrol might be
      mediated through an Nrf2-dependent mechanism.

PMID- 25979660
TI  - Protein-losing enteropathy in a patient on ketogenic diet for limbic encephalitis
      -treatment effect or underlying pathology?

PMID- 25979661
TI  - An Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Children
      With Epilepsy Receiving Treatment of Valproic Acid.
AB  - AIM: We investigated the peripapillary retinal nerve fiber layer thickness with
      optical coherence tomography in epileptic children receiving valproic acid
      monotherapy. MATERIALS AND METHODS: The study was conducted on children aged 8-16
      years who were undergoing valproic acid monotherapy for epilepsy. The study group
      comprised a total of 40 children who met the inclusion criteria and 40 healthy
      age- and sex-matched children as a control group. Children with at least a 1-year
      history of epilepsy and taking 10-40 mg/kg/day treatment were included in the
      study. Peripapillary retinal nerve fiber layer thickness measurements were
      performed using Cirrus HD optical coherence tomography. All children and parents
      were informed about the study and informed consent was obtained from the parents
      of all the participants. RESULTS: The study group included 21 girls and 19 boys
      with a mean age of 10.6 +/- 2.3 years. According to the results of optical
      coherence tomography measurements, the mean peripapillary retinal nerve fiber
      layer thickness was 91.6 +/- 9.7 in the patient group and 95.5 +/- 7.4 MUm in the
      control group (P < 0.05). The superior peripapillary retinal nerve fiber layer
      thickness was 112.0 +/- 13.2 in the patient group and 120.0 +/- 14.7 MUm in the
      control group (P < 0.02). According to the results of both measurements, the
      peripapillary retinal nerve fiber layer thickness was significantly lower in the
      patient group. Neither color vision loss nor visual field examination abnormality
      could be documented. CONCLUSION: According to the optical coherence tomography
      measurements, the average and superior peripapillary retinal nerve fiber layer
      thicknesses were thinner in patients with epilepsy who were receiving valproic
      acid monotherapy compared with healthy children. This situation can lead to
      undesirable results in terms of eye health. New studies are needed to investigate
      whether these findings are the result of epilepsy or can be attributed to
      valproic acid and whether there are adverse effects of valproic acid later in
      life.

PMID- 25979659
TI  - Mechanisms linking mtDNA damage and aging.
AB  - In the past century, considerable efforts were made to understand the role of
      mitochondrial DNA (mtDNA) mutations and of oxidative stress in aging. The classic
      mitochondrial free radical theory of aging, in which mtDNA mutations cause
      genotoxic oxidative stress, which in turn creates more mutations, has been a
      central hypothesis in the field for decades. In the past few years, however, new
      elements have discredited this original theory. The major sources of
      mitochondrial DNA mutations seem to be replication errors and failure of the
      repair mechanisms, and the accumulation of these mutations as observed in aged
      organisms seems to occur by clonal expansion and not to be caused by a reactive
      oxygen species-dependent vicious cycle. New hypotheses of how age-associated
      mitochondrial dysfunction may lead to aging are based on the role of reactive
      oxygen species as signaling molecules and on their role in mediating stress
      responses to age-dependent damage. Here, we review the changes that mtDNA
      undergoes during aging and the past and most recent hypotheses linking these
      changes to the tissue failure observed in aging. 

PMID- 25979662
TI  - Brain malformations in a patient with deletion 2p16.1: A refinement of the
      phenotype to BCL11A.
AB  - Microdeletions of 2p15-16.1 have been reported in 15 patients with a recognizable
      syndrome of dysmorphic features, intellectual disability and microcephaly. Facial
      features include telecanthus, short palpebral fissures, epicanthal folds, a broad
      nasal root, smooth and long philtrum and large ears. Brain malformations can be
      observed in this syndrome and include hypoplasia of the corpus callosum and a
      simplified cortical gyral pattern. Case reports have narrowed the critical region
      of the neurodevelopmental phenotype to a region that spans the B-cell
      CLL/lymphoma 11A (BCL11A) gene. Here we present a 3-year-old normocephalic girl
      with moderate development delay and dysmorphic features including a prominent
      forehead, telecanthus, depressed nasal bridge, thin upper vermilion and a small
      chin. Magnetic resonance imaging shows enlargement of the lateral, third and
      fourth ventricles and hypoplastic corpus callosum, cerebellar vermis and pons.
      Array CGH revealed a 0.875 Mb de novo deletion at 2p16.1 that includes only
      BCL11A. The moderate delays, hypoplastic and dysmorphic corpus callosum and
      hippocampi and the facial features are in keeping with the previously described
      2p15-16.1 microdeletion syndrome. However, hypoplasia of the pons and cerebellum
      are not commonly recognized features and are reminiscent of the brain
      malformations observed in individuals with a mutation in CASK. CASK is known to
      interact with BCL11A in the normal growth of axons. This case report highlights
      the role of BCL11A in 2p15-16.1 microdeletion syndrome and the unique phenotype
      suggests a common pathway for BCL11A and other genes in neurodevelopment. 

PMID- 25979663
TI  - [Foods related to the novel 'don quixote de la mancha'. did they follow the
      healthy nutritional recommendations which are advised nowadays?].
AB  - It is known that Miguel de Cervantes's novel 'Don Quixote de La Mancha' has done
      and is still doing a great contribution to the universal literature. A book that
      has reached such category and grows in number of its readers, shows multiple
      dimensions for its study. One of them is nutrition. One of the aims of this study
      has been to value and expound, according to their own nutrients, the kinds of
      food cited in 'The Quixote' and in the times of Cervantes. This has allowed the
      comparison made between ways of nutrition in La Mancha and in Catalonia, as well
      as the regions situated at the beginning and end of the itinerary covered by its
      main characters Don Quixote and Sancho Panza. The evaluation of the nutrients in
      the middle part of the itinerary, placed mainly in Aragon, has not been
      considered in this study. Another purpose has been to check if these nutrients
      followed the current recommendations of the Spanish Society of Arteriosclerosis
      and other valid agreements at the moment. 

PMID- 25979664
TI  - Circadian regulation of slow waves in human sleep: Topographical aspects.
AB  - Slow waves (SWs, 0.5-4Hz) in field potentials during sleep reflect synchronized
      alternations between bursts of action potentials and periods of membrane
      hyperpolarization of cortical neurons. SWs decline during sleep and this is
      thought to be related to a reduction of synaptic strength in cortical networks
      and to be central to sleep's role in maintaining brain function. A central
      assumption in current concepts of sleep function is that SWs during sleep, and
      associated recovery processes, are independent of circadian rhythmicity. We
      tested this hypothesis by quantifying all SWs from 12 EEG derivations in 34
      participants in whom 231 sleep periods were scheduled across the circadian cycle
      in a 10-day forced-desynchrony protocol which allowed estimation of the separate
      circadian and sleep-dependent modulation of SWs. Circadian rhythmicity
      significantly modulated the incidence, amplitude, frequency and the slope of the
      SWs such that the peaks of the circadian rhythms in these slow-wave parameters
      were located during the biological day. Topographical analyses demonstrated that
      the sleep-dependent modulation of SW characteristics was most prominent in
      frontal brain areas whereas the circadian effect was similar to or greater than
      the sleep-dependent modulation over the central and posterior brain regions. The
      data demonstrate that circadian rhythmicity directly modulates characteristics of
      SWs thought to be related to synaptic plasticity and that this modulation depends
      on topography. These findings have implications for the understanding of local
      sleep regulation and conditions such as ageing, depression, and neurodegeneration
      which are associated with changes in SWs, neural plasticity and circadian
      rhythmicity. 

PMID- 25979665
TI  - The hemodynamic response to somatosensory stimulation in mice depends on the
      anesthetic used: Implications on analysis of mouse fMRI data.
AB  - In recent years, the number of functional MRI (fMRI) studies in mice has been
      rapidly increasing. Technological improvements provide the sensitivity required
      to match the high demands on spatial and temporal resolution and to analyze fast
      and small signal components of the fMRI response. Yet, the interpretation of
      mouse fMRI data largely relies on assumptions that were uncritically adopted from
      previous research in humans or rats. Here, we show based on a large dataset
      employing an innocuous electrical stimulation paradigm, that (1) the shape of the
      HRF shapes comprises significant transient signal components; correspondingly
      analysis procedures have to account for this dynamic nature and allow for
      variable response functions. (2) The effects of the anesthetics are crucial in
      determining the shape of the hemodynamic response function (HRF) and also
      influence the spatial specificity of BOLD signal. (3) The dominant systemic
      confounding contributions elicited by stimulus-evoked cardiovascular responses
      observed in mouse fMRI when applying block stimuli may be largely avoided by a
      milder event-related design applying a randomly spaced single pulse train
      (RSSPT). Thereby the spatial specificity of the fMRI response is largely
      retained. We conclude that the sensitivity, specificity and interpretability of
      stimulus-evoked BOLD signals in mice can be improved by combining appropriate
      stimulation paradigms with analysis procedures that include adapted HRFs. 

PMID- 25979666
TI  - Anatomical changes within the medullary dorsal horn in chronic temporomandibular
      disorder pain.
AB  - Accumulated evidence from experimental animal models suggests that neuroplastic
      changes at the dorsal horn are critical for the maintenance of various chronic
      musculoskeletal pain conditions. However, to date, no study has specifically
      investigated whether neuroplastic changes also occur at this level in humans.
      Using brain imaging techniques, we sought to determine whether anatomical changes
      were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in
      subjects with the chronic musculoskeletal pain. In twenty-two subjects with
      painful temporomandibular disorders (TMDs) and forty pain-free controls voxel
      based morphometry of T1-weighted anatomical images and diffusion tensor images
      were used to assess regional grey matter volume and microstructural changes
      within the brainstem and, in addition, the integrity of ascending pain pathways.
      Voxel based morphometry revealed significant regional grey matter volume
      decreases in the medullary dorsal horn, in conjunction with alterations in
      diffusivity properties, namely an increase in mean diffusivity, in TMD subjects.
      Volumetric and mean diffusivity changes also occurred in TMD subjects in regions
      of the descending pain modulation system, including the midbrain periaqueductal
      grey matter and nucleus raphe magnus. Finally, tractography revealed altered
      diffusivity properties, namely decreased fractional anisotropy, in the root entry
      zone of the trigeminal nerve, the spinal trigeminal tract and the ventral
      trigeminothalamic tracts of TMD subjects. These data reveal that chronic
      musculoskeletal pain in humans is associated with discrete alterations in the
      anatomy of the medullary dorsal horn, as well as its afferent and efferent
      projections. These neural changes may be critical for the maintenance of
      pathological pain. 

PMID- 25979668
TI  - Lateralization patterns of covert but not overt movements change with age: An EEG
      neurofeedback study.
AB  - The mental practice of movements has been suggested as a promising add-on therapy
      to facilitate motor recovery after stroke. In the case of mentally practised
      movements, electroencephalogram (EEG) can be utilized to provide feedback about
      an otherwise covert act. The main target group for such an intervention are
      elderly patients, though research so far is largely focused on young populations
      (<30 years). The present study therefore aimed to examine the influence of age on
      the neural correlates of covert movements (CMs) in a real-time EEG neurofeedback
      framework. CM-induced event-related desynchronization (ERD) was studied in young
      (mean age: 23.6 years) and elderly (mean age: 62.7 years) healthy adults.
      Participants performed covert and overt hand movements. CMs were based on
      kinesthetic motor imagery (MI) or quasi-movements (QM). Based on previous studies
      investigating QM in the mu frequency range (8-13Hz) QM were expected to result in
      more lateralized ERD% patterns and accordingly higher classification accuracies.
      Independent of CM strategy the elderly were characterized by a significantly
      reduced lateralization of ERD%, due to stronger ipsilateral ERD%, and in
      consequence, reduced classification accuracies. QM were generally perceived as
      more vivid, but no differences were evident between MI and QM in ERD% or
      classification accuracies. EEG feedback enhanced task-related activity
      independently of strategy and age. ERD% measures of overt and covert movements
      were strongly related in young adults, whereas in the elderly ERD% lateralization
      is dissociated. In summary, we did not find evidence in support of more
      pronounced ERD% lateralization patterns in QM. Our finding of a less lateralized
      activation pattern in the elderly is in accordance to previous research and with
      the idea that compensatory processes help to overcome neurodegenerative changes
      related to normal ageing. Importantly, it indicates that EEG neurofeedback
      studies should place more emphasis on the age of the potential end-users.

PMID- 25979667
TI  - Between-network connectivity occurs in brain regions lacking layer IV input.
AB  - To better understand the cortical circuitry underlying connectivity between large
      scale neural networks, we develop a novel, data-driven approach to identify
      potential integration subregions. Between-network connectivity (BNC) associated
      with any anatomical region is the amount of connectivity between that point and
      all large-scale networks, as measured using simple and multiple correlations. It
      is straightforward to calculate and applicable to functional networks identified
      using independent components analysis. We calculated BNC for all fMRI voxels
      within the brain and compared the results to known regional cytoarchitectural
      patterns. Based on previous observations of the relationship between macroscopic
      connectivity and microscopic cytoarchitecture, we predicted that areas with high
      BNC will be located in paralimbic subregions with an undifferentiated laminar
      structure. Results suggest that the anterior insula and dorsal posterior
      cingulate cortices play prominent roles in information integration.
      Cytoarchitecturely, these areas show agranular or dysgranular cytologies with
      absent or disrupted cortical layer IV. Since layer IV is the primary recipient of
      feed-forward thalamocortical connections, and due to the exclusive nature of
      driving connections to this layer, we suggest that the absence of cortical layer
      IV might allow for information to be exchanged across networks, and is an
      organizational characteristic of brain-subregions serving as inter-network
      communication hubs. 

PMID- 25979669
TI  - Chikungunya: Evolutionary history and recent epidemic spread.
AB  - Chikungunya virus (CHIKV) has a long history of emergence into urban transmission
      cycles from its ancestral, enzootic, sylvatic foci in Sub-Saharan Africa, most
      recently spreading to the Americas beginning in 2013. Since 2004, reemergence has
      resulted in millions of cases of severe, debilitating and often chronic
      arthralgia on five continents. Here, we review this history based on phylogenetic
      studies, and discuss probable future spread and disease in the Americas. We also
      discuss a series of mutations in the recently emerged Indian Ocean Lineage that
      has adapted the virus for transmission for the first time by the Aedes albopictus
      urban mosquito vector, and compare CHIKV to other arboviruses with and without
      similar histories of urbanization. This article forms part of a symposium in
      Antiviral Research on "Chikungunya discovers the New World." 

PMID- 25979670
TI  - Magnetic resonance-based thermometry during laser ablation on ex-vivo swine
      pancreas and liver.
AB  - Laser Ablation (LA) is a minimally-invasive procedure for tumor treatment. LA
      outcomes depend on the heat distribution inside tissues and require accurate
      temperature measurement during the procedure. Magnetic resonance imaging (MRI)
      allows a non-invasive and three-dimensional thermometry of the organ undergoing
      LA. In this study, the temperature distribution within two swine pancreases and
      three swine livers undergoing LA (Nd:YAG, power: 2 W, treatment time: 4 min) was
      monitored by a 1.5-T MR scanner, utilizing two T1-weighted sequences (IRTF and
      SRTF). The signal intensity in four regions of interest, placed at different
      distances from the laser applicator, was related to temperature variations
      monitored in the same regions by twelve fiber Bragg grating sensors. The
      relationship between the signal intensity and temperature increase was calculated
      to obtain the calibration curve and to evaluate accuracy, sensibility and
      precision of each sequence. This is the first study of MR-based thermometry
      during LA on pancreas. More specifically, the IRTF sequence provides the highest
      temperature sensitivity in both liver (1.8 +/- 0.2  degrees C(-1)) and pancreas
      (1.8 +/- 0.5  degrees C(-1)) and the lowest precision and accuracy. SRTF sequence
      on pancreas presents the highest accuracy and precision (MODSFRT = -0.1  degrees
      C and LOASFRT = [-2.3; 2.1]  degrees C).

PMID- 25979671
TI  - Partial trisomy 4q and partial monosomy 9p in a girl with choanal atresia and
      various dysmorphic findings.
AB  - We report a new-born girl with partial trisomy of 4q28-qter and partial monosomy
      of 9p24-9ter. Our patient has choanal atresia, hypertelorism, wide nasal bridge,
      high arched palate, discrete nipples, heart defects, myoclonic seizures and
      various dysmorphic findings. Standard chromosomal analysis with G-banding with
      Trypsin-Giemsa revealed 46,XX,der(9)t(4;9)(q28;p24) resulting from the mother's
      t(4,9) (q28;p24) karyotype. Deletions of the terminal part of 9p and partial
      trisomy of chromosome 4q are rare chromosomal alterations. To our knowledge, this
      is the first report of choanal atresia in a patient with a partial trisomy of
      4q28-qter and partial monosomy 9p24-9ter combination, which were detected by
      integrated cytogenetic and genomic analysis.

PMID- 25979672
TI  - Molecular cloning and expression analysis of scd1 gene from large yellow croaker
      Larimichthys crocea under cold stress.
AB  - Desaturation of fatty acids is an important adaptation mechanism to maintain
      membrane fluidity under cold stress. To comprehend the mechanism of adaptation to
      low temperatures in fish, we investigated stearoyl-CoA desaturase 1 (SCD1)
      endocrine expression in the process of cold acclimation from 15 degrees C to 7
      degrees C in Larimichthys crocea. The cDNA and genomic sequences of scd1 were
      cloned and characterized and named as Lcscd1. The cDNA encoded an iron-containing
      protein of 337 amino acids with functional motifs. The full-length genome
      sequence of Lcscd1 was composed of 2556 nucleotides, including five exons and
      four introns. Tissue expression profiles by qPCR and western blot analysis
      revealed that Lcscd1 was highly expressed in the liver, followed by the brain.
      The expression of Lcscd1 mRNA in the liver was firstly down-regulated from 15
      degrees C to 11 degrees C, and then up-regulated until the first day of 7 degrees
      C, followed by a decline until the last day. In the brain, the expression showed
      no significant change from 15 degrees C to 9 degrees C, but then significantly
      increased until the last day of 7 degrees C. SCD1 protein expression in the liver
      decreased from 15 degrees C to the first day of 7 degrees C, and then gradually
      recovered to the starting level. In the brain, SCD1 protein expression maintained
      rising trends in the whole process. Immunoelectron microscopic analysis showed
      that SCD1 was localized in fat granules, mitochondria and granular endoplasmic
      reticulum of hepatic cells, but only in mitochondria of encephalic cells. The
      results above suggested that SCD1 expression was responsive to both cold and
      starvation stresses in the liver, but only to cold stress in the brain. In
      conclusion, these findings suggested that SCD1 may be involved in fish adaptation
      to cold stress.

PMID- 25979673
TI  - Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage
      in a rat model via PI3K/Akt signaling pathway.
AB  - In this study, we aimed to assess the neuroprotective effect of sevoflurane
      preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague
      Dawley rats were divided into six groups: sham operated group, cerebral focal
      ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%)
      group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane
      preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All
      subjects were euthanized 2days post-surgery and their hippocampus tissues were
      removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
      (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus
      tissue samples were examined histopathologically. Results showed that significant
      difference in antioxidant, immunity indexes, and apoptosis-related protein
      expression was detected in hippocampus tissue between sham-operated control and
      CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced
      MDA, IL-1beta, IL-6, IL-10 and TNF-alpha levels and enhanced antioxidant enzyme
      activities in hippocampus tissue of CIR+SP groups compared to CIR group. In
      addition, sevoflurane preconditioning significantly dose-dependently upregulated
      PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in
      hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded
      that sevoflurane preconditioning demonstrates a strong and ameliorative effect on
      cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane
      preconditioning are associated with its properties of anti-apoptosis and anti
      oxidation as well as regulation of PI3K and p-Akt signal activation.

PMID- 25979674
TI  - The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage is
      susceptible to increased weight gain when fed a high-fat diet: Confirmation of a
      gene-diet interaction.

PMID- 25979675
TI  - A mutation in the NLRC5 promoter limits NF-kappaB signaling after Salmonella
      Enteritidis infection in the spleen of young chickens.
AB  - To date, the functions of the NLRC5 in chickens remain undefined. In the current
      study, chicken NLRC5 was cloned and an A1017G mutation was detected in its
      promoter region. The relative expression levels of the NLRC5 and key NF-kappaB
      pathway genes, IKKalpha, IKKbeta, NF-kappaB, IL-6, IL-1beta and IFN-gamma, in the
      spleens of wild and mutant type birds, AA and GG, were determined using FQ-PCR at
      7 day post-infection (DPI) with Salmonella Enteritidis. Additionally, the
      bacterial burden in the caecum and various immune response parameters were
      measured to evaluate immune responses. All of the examined immune response
      parameters were significantly different between the AA chickens and the GG
      chickens. Specifically, the mRNA expression levels of IKKalpha, NF-kappaB, IL-6,
      IL-1beta and IFN-gamma were higher in AA chickens than those in GG chickens,
      while the mRNA expression levels of NLRC5 were lower in AA chickens than those in
      GG chickens (P<0.05). Moreover, the mRNA expression levels of TLR4 and MyD88 were
      not affected in either group. Collectively, considering former NLRC5 functional
      study in vitro, the wild genotype birds presented with better resistance to
      Salmonella Enteritidis through the actions of the NLRC5 and subsequent inhibition
      of the NF-kappaB pathway in chickens.

PMID- 25979677
TI  - The Jurassic Bajanzhargalanidae (Insecta: Grylloblattida?): New genera and
      species, and data on postabdominal morphology.
AB  - The presumed phylogenetic link between extant ice-crawlers (Grylloblattidae =
      'crown-Grylloblattida') and fossil species of the taxon concept Grylloblattida
      sensu Storozhenko (2002) is essentially based on postabdominal morphology.
      However, the fossil data are limited, and the interpretation is open to debate.
      Here we investigate a sample of a poorly known fossil 'grylloblattidan' family,
      the Bajanzhargalanidae, collected from the Daohugou locality (Middle Jurassic,
      China). We describe Sinonele fangi gen. nov., sp. nov., Sinonele hei gen. nov.,
      sp. nov., Sinonele phasmoides gen. nov., sp. nov., and Sinonele mini gen. nov.,
      sp. nov. Thanks to the abundance and exceptional preservation of the material, we
      could document wing venation intra-specific variability, provide cues to identify
      male and female individuals, describe and tentatively interpret various body
      structures of both sexes, and discuss them with a broad pterygotan phylogenetic
      perspective. The Bajanzhargalanidae exhibit a puzzling combination of
      postabdominal characters leaving us inconclusive on their affinities, or lack
      thereof, with crown-Grylloblattida. Our contribution suggests that a substantial
      effort will be needed to further investigate postabdominal structures from
      comparatively ancient fossil insects preserved as rock imprints, because of their
      broad morphological disparity.

PMID- 25979676
TI  - High and low frequency subharmonic imaging of angiogenesis in a murine breast
      cancer model.
AB  - This project compared quantifiable measures of tumor vascularity obtained from
      contrast-enhanced high frequency (HF) and low frequency (LF) subharmonic
      ultrasound imaging (SHI) to 3 immunohistochemical markers of angiogenesis in a
      murine breast cancer model (since angiogenesis is an important marker of
      malignancy and the target of many novel cancer treatments). Nineteen athymic,
      nude, female rats were implanted with 5*10(6) breast cancer cells (MDA-MB-231) in
      the mammary fat pad. The contrast agent Definity (Lantheus Medical Imaging, N
      Billerica, MA) was injected in a tail vein (dose: 180MUl/kg) and LF pulse
      inversion SHI was performed with a modified Sonix RP scanner (Analogic
      Ultrasound, Richmond, BC, Canada) using a L9-4 linear array
      (transmitting/receiving at 8/4MHz in SHI mode) followed by HF imaging with a Vevo
      2100 scanner (Visualsonics, Toronto, ON, Canada) using a MS250 linear array
      transmitting and receiving at 24MHz. The radiofrequency data was filtered using a
      4th order IIR Butterworth bandpass filter (11-13MHz) to isolate the subharmonic
      signal. After the experiments, specimens were stained for endothelial cells
      (CD31), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2).
      Fractional tumor vascularity was calculated as contrast-enhanced pixels over all
      tumor pixels for SHI, while the relative area stained over total tumor area was
      calculated from specimens. Results were compared using linear regression
      analysis. Out of 19 rats, 16 showed tumor growth (84%) and 11 of them were
      successfully imaged. HF SHI demonstrated better resolution, but weaker signals
      than LF SHI (0.06+/-0.017 vs. 0.39+/-0.059; p<0.001). The strongest overall
      correlation in this breast cancer model was between HF SHI and VEGF (r=-0.38;
      p=0.03). In conclusion, quantifiable measures of tumor neovascularity derived
      from contrast-enhanced HF SHI appear to be a better method than LF SHI for
      monitoring angiogenesis in a murine xenograft model of breast cancer
      (corresponding in particular to the expression of VEGF); albeit based on a
      limited sample size. 

PMID- 25979678
TI  - A framework for evaluating the cost-effectiveness of patient decision aids: A
      case study using colorectal cancer screening.
AB  - OBJECTIVE: Patient decision aids are important tools for facilitating balanced,
      evidence-based decision making. However, the potential of decision aids to lower
      health care utilization and costs is uncertain; few studies have investigated the
      cost-effectiveness of decision aids that change patient behavior. Using an
      example of a decision aid for colorectal cancer screening, we provide a framework
      for analyzing the cost-effectiveness of decision aids. METHODS: A decision
      analytic model with two strategies (decision aid or no decision aid) was used to
      calculate expected costs in U.S. dollars and benefits measured in life-years
      saved (LYS). Data from a systematic review of ten studies about decision aid
      effectiveness was used to calculate the percentage increase in the number of
      people choosing screening instead of no screening. We then calculated the
      incremental cost per LYS with the use of the decision aid. RESULTS: The no
      decision aid strategy had an expected cost of $3023 and yielded 18.19 LYS. The
      decision aid strategy cost $3249 and yielded 18.20 LYS. The incremental cost
      effectiveness ratio for the decision aid strategy was $36,126 per LYS. Results
      were sensitive to the cost of the decision aid and the percentage change in
      behavior caused by the decision aid. CONCLUSIONS: This study provides proof-of
      concept evidence for future studies examining the cost-effectiveness of decision
      aids. The results suggest that decision aids can be beneficial and cost
      effective.

PMID- 25979679
TI  - Predictive Factors Associated With Acute Ocular Involvement in Stevens-Johnson
      Syndrome and Toxic Epidermal Necrolysis.
AB  - PURPOSE: To suggest an objective score for grading the acute ocular severity of
      Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to
      determine predictive factors for severe acute ocular involvement such as ocular
      surface epithelial defect and/or pseudomembrane formation. DESIGN: Retrospective
      cohort study. METHODS: The medical records of SJS (n = 87) and TEN (n = 48)
      patients between 2005 and 2007 were reviewed. An acute ocular severity score was
      determined on a scale from 0 to 3 (none, mild, severe, and very severe) according
      to the existence of hyperemia, corneal or conjunctival epithelial defect, and
      pseudomembrane formation. The associations between the severe acute ocular
      involvement and factors such as patient age, exposed drugs, systemic severity,
      and the prevalence of ocular sequelae were examined. RESULTS: The number of cases
      with score grade 0, 1, 2, and 3 was 19 (21.8%), 31 (35.6%), 22 (25.3%), and 15
      (17.2%) in 87 SJS cases and 12 (25.0%), 11 (22.9%), 17 (35.4%), and 8 (16.7%) in
      48 TEN cases. Multivariate logistic regression analysis revealed that patient age
      (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; P = .007) and
      nonsteroidal anti-inflammatory drugs NSAIDs or cold remedies (OR, 2.58; 95% CI,
      1.26-5.29; P = .010) were predictive factors for severe acute ocular involvement.
      The prevalence of visual disturbance and eye dryness increased according to the
      increase of acute ocular severity (P = .001 and P = .007 in SJS; P = .007 and P =
      .014 in TEN, respectively). CONCLUSIONS: At the onset of SJS/TEN, strict
      attention should be paid to ocular involvement in young patients and in patients
      exposed to NSAIDs or cold remedies.

PMID- 25979681
TI  - Uterine Leiomyoma and Prolapse in a Live-stranded Atlantic Spotted Dolphin
      (Stenella frontalis).
AB  - A uterine prolapse associated with a leiomyoma (fibroid) was observed in a live
      stranded Atlantic spotted dolphin (Stenella frontalis). A 7 cm segment of the
      reproductive tract including the cervix, uterine neck and caudal uterine body had
      intussuscepted and prolapsed into the cranial vaginal vault. In the leading edge
      of the intussuscepted/prolapsed uterine wall was a 6 * 3 * 3.5 cm leiomyoma
      expanding the myometrium. The leiomyoma and prolapse were associated with
      necrotizing exposure endometritis. This is the first report of a uterine prolapse
      associated with a leiomyoma in a cetacean. This lesion was believed to be the
      underlying cause of the live stranding. 

PMID- 25979680
TI  - E-mental health care among young adults and help-seeking behaviors: a transversal
      study in a community sample.
AB  - BACKGROUND: The Internet is widely used by young people and could serve to
      improve insufficient access to mental health care. Previous information on this
      topic comes from selected samples (students or self-selected individuals) and is
      incomplete. OBJECTIVE: In a community sample of young adults, we aimed to
      describe frequency of e-mental health care study-associated factors and to
      determine if e-mental health care was associated with the use of conventional
      services for mental health care. METHODS: Using data from the 2011 wave of the
      TEMPO cohort study of French young adults (N=1214, aged 18-37 years), we examined
      e-mental health care and associated factors following Andersen's behavioral
      model: predisposing factors (age, sex, educational attainment, professional
      activity, living with a partner, children, childhood negative events, chronic
      somatic disease, parental history of depression), enabling factors (social
      support, financial difficulties, parents' income), and needs-related factors
      (lifetime major depression or anxiety disorders, suicidal ideation, ADHD,
      cannabis use). We compared traditional service use (seeking help from a general
      practitioner, a psychiatrist, a psychologist; antidepressant or
      anxiolytics/hypnotics use) between participants who used e-mental health care
      versus those who did not. RESULTS: Overall, 8.65% (105/1214) of participants
      reported seeking e-mental health care in case of psychological difficulties in
      the preceding 12 months and 15.7% (104/664) reported psychological difficulties.
      Controlling for all covariates, the likelihood of e-mental health care was
      positively associated with 2 needs-related factors, lifetime major depression or
      anxiety disorder (OR 2.36, 95% CI 1.36-4.09) and lifetime suicidal ideation (OR
      1.91, 95% CI 1.40-2.60), and negatively associated with a predisposing factor:
      childhood life events (OR 0.60, 95% CI 0.38-0.93). E-mental health care did not
      hinder traditional care, but was associated with face-to-face psychotherapy
      (66.2%, 51/77 vs 52.4%, 186/355, P=.03). CONCLUSIONS: E-mental health care
      represents an important form of help-seeking behavior for young adults.
      Professionals and policy makers should take note of this and aim to improve the
      quality of online information on mental health care and to use this fact in
      clinical care.

PMID- 25979682
TI  - Interobserver Reproducibility of Histological Grading of Canine Simple Mammary
      Carcinomas.
AB  - Histological grading of canine mammary carcinomas (CMCs) has been performed using
      an adaptation of the human Nottingham method. The histological grade could be a
      prognostic factor in CMC; however, no data are available concerning interobserver
      variability in grading. In this study we analyzed the interobserver
      reproducibility between three observers when assigning individual parameter
      scores and grade to 46 CMCs. The influence of tumour size and vascular invasion
      and/or lymph node metastases on the odds of grading disagreement was also
      evaluated. The mean kappa values were 0.71, 0.51, 0.69 and 0.70 for tubule
      formation, nuclear pleomorphism, mitotic counts and grade, respectively. There
      was moderate to good agreement in scoring parameters and tumour grading, with
      nuclear pleomorphism being least reproducible. These findings are similar to
      those of human studies. The odds of grading disagreement increased with tumour
      size, but decreased with the presence of vascular invasion and/or lymph node
      metastases. Individual scoring differences were moderated by reaching a consensus
      between two observers. 

PMID- 25979683
TI  - Caries, Periodontal Disease, Supernumerary Teeth and Other Dental Disorders in
      Swedish Wild Boar (Sus scrofa).
AB  - Between January and December 2013, the dental and periodontal health of 99
      Swedish wild boars (Sus scrofa) was investigated. Sampling occurred in
      conjunction with routine hunting at six large estates in the southern and middle
      parts of Sweden. All six of the estates use supplemental feeding. The weight of
      the animals, their sex and their dates of death were noted. Age was estimated
      using tooth eruption and tooth replacement patterns. The oral cavity was
      inspected and abnormalities were recorded on a dental chart modified for wild
      boars. The findings included supernumerary teeth, absence of teeth, mild class II
      malocclusion, severe tooth wear, periodontitis, calculus, caries, tooth fractures
      and the presence of enamel defects. Swedish wild boars suffer from different
      dental lesions and the impact of supplemental feeding on dental and periodontal
      health is still to be investigated. 

PMID- 25979684
TI  - Comorbidity associated with obesity in a large population: The APNA study.
AB  - BACKGROUND: Overweight and obesity are major causes of comorbidities which can
      lead to further morbidity and mortality. The main objective of the present study
      was to estimate the comorbidity associated with obesity in 40,010 patients
      attending Primary Health Care Centres in Navarra. METHODS: It is a descriptive
      cross-sectional study. The association of overweight and obesity in different
      diseases was studied. Odds ratios (OR) adjusted for age and sex were calculated
      by unconditional logistic regression, using as reference patients with body mass
      index (BMI) lower than 25 kg/m(2). RESULTS: Increasing BMI is associated with
      glucose intolerance (OR: 1.07; 95% CI: 1.06-1.08), dyslipidemia (OR: 1.04; 95%
      CI: 1.03-1.04), hypertension (OR: 1.12; 95% CI: 1.12-1.13), type 2 diabetes (OR:
      1.11; 95% CI: 1.10-1.11), kidney failure (OR: 1.04; 95% CI: 1.03-1.05), and
      osteoarthritis (OR: 1.06; 95% CI: 1.05-1.06). Moreover, all the degrees of
      obesity are associated with asthma (OR type I obesity: 1.33; OR type II obesity:
      1.69; OR type III obesity: 1.75), heart failure (OR type I obesity: 1.68; OR type
      II obesity: 2.78; OR type III obesity: 4.35), and severe mental disorders (OR
      type I obesity: 2.02; OR type II obesity: 2.33; OR type III obesity: 2.50). Type
      II and morbid obesity are associated with chronic obstructive pulmonary disease
      and depression. CONCLUSION: Our study showed a positive association of the
      overweight and obesity with glucose intolerance, dyslipidemia, type 2 diabetes,
      hypertension, osteoarthritis, and kidney failure. An interesting point is the
      association of higher levels of BMI with depression.

PMID- 25979685
TI  - Gene expression related to lipid and glucose metabolism in white adipose tissue.
AB  - PROBLEM: A number of endogenous and external factors influence the development of
      obesity. However, the factors responsible for these differences in obesity
      pathogenesis between males and females are largely unknown. METHODS: We
      investigated the expression of 35 genes related to lipid and glucose metabolism
      and to receptors for insulin signaling in white adipose tissue (WAT) of 8-week
      old 129/Sv mice and mice fed standard diet (STD) or high fat diet (HFD) for 35
      weeks in males and females. RESULTS: At 8 weeks, the expression levels of two
      genes for fatty acid synthesis, Acaca and Fasn, were higher in females than in
      males. Female mice fed a STD for 35 weeks also had higher expression levels of an
      additional four genes related to glucose transporters (Slc2a1 and Slc2a4) and
      adipokines (Adipoq and Nampt). The expression levels of these six genes were also
      higher in females than in males fed a HFD for 35 weeks. At 43 weeks old, the
      female-to-male expression ratio of these six genes was similar for the STD and
      HFD groups. Furthermore, glucose tolerance testing showed that the half-life for
      the elimination of elevated blood glucose was shorter in females than males,
      although blood glucose parameters were generally similar between females and
      males. CONCLUSIONS: These findings suggest that sex and aging may cause diet
      independent differences in gene expression levels in female and male mice, and
      that higher expression of these genes in females could contribute to higher
      metabolic activity and resistance to obesity compared with males.

PMID- 25979686
TI  - Humeral Head Reconstruction With Osteochondral Allograft Transplantation.
AB  - PURPOSE: To synthesize, in a systematic review, the available clinical evidence
      of osteochondral allograft transplants for large osteochondral defects of the
      humeral head. METHODS: The Medline, Embase, and Cochrane databases were searched
      for studies reporting clinical or radiographic outcomes of osteochondral
      allograft transplantation for humeral head defects. Descriptive statistics were
      provided for all outcomes. After checking for data normality, we compared
      postoperative and preoperative values using the Student t test. RESULTS: We
      included 12 studies (8 case reports and 4 case series) in this review. The study
      group consisted of 35 patients. The mean age was 35.4 +/- 18.1 years; 77% of
      patients were male patients. Thirty-three patients had large Hill-Sachs lesions
      due to instability, 1 had an osteochondritis dissecans lesion, and 1 had an
      iatrogenic lesion after resection of synovial chondromatosis. The mean lesion
      size was 3 +/- 1.4 cm (anteroposterior) by 2.25 +/- 0.3 cm (medial-lateral),
      representing on average 40.5% +/- 4.73% of the native articular surface. Of the
      35 patients, 3 received a fresh graft, with all others receiving frozen grafts.
      Twenty-three femoral heads, 10 humeral heads, and 2 sets of osteochondral plugs
      were used. The mean length of follow-up was 57 months. Significant improvements
      were seen in forward flexion at 6 months (68 degrees  +/- 18.1 degrees , P <
      .001), forward flexion at 12 months (83.42 degrees  +/- 18.3 degrees , P < .001),
      and external rotation at 12 months (38.72 degrees  +/- 18.8 degrees , P < .001).
      American Shoulder and Elbow Surgeons scores improved by 14 points (P = .02).
      Radiographic studies at final follow-up showed allograft necrosis in 8.7% of
      cases, resorption in 36.2%, and glenohumeral arthritic changes in 35.7%.
      Complication rates were between 20% and 30%, and the reoperation rate was 26.67%.
      Although only 3 patients received fresh allografts, there were no reports of
      graft resorption, necrosis, or arthritic changes in these patients. CONCLUSIONS:
      Humeral head allograft-most commonly used in the setting of large Hill-Sachs
      lesions due to instability-has shown significant improvements in shoulder motion
      and American Shoulder and Elbow Surgeons scores as far as 1 year postoperatively.
      Return-to-work rates and satisfaction levels are high after the intervention.
      Complication and reoperation rates are substantial, although it is possible that
      use of fresh allograft tissue may result in less resorption and necrosis. LEVEL
      OF EVIDENCE: Level V, systematic review of Level IV and V studies.

PMID- 25979687
TI  - Arthroscopic Transtibial Pullout Repair for Posterior Medial Meniscus Root Tears:
      A Systematic Review of Clinical, Radiographic, and Second-Look Arthroscopic
      Results.
AB  - PURPOSE: To systematically review the results of arthroscopic transtibial pullout
      repair (ATPR) for posterior medial meniscus root tears. METHODS: A systematic
      electronic search of the PubMed database and the Cochrane Library was performed
      in September 2014 to identify studies that reported clinical, radiographic, or
      second-look arthroscopic outcomes of ATPR for posterior medial meniscus root
      tears. Included studies were abstracted regarding study characteristics, patient
      demographic characteristics, surgical technique, rehabilitation, and outcome
      measures. The methodologic quality of the included studies was assessed with the
      modified Coleman Methodology Score. RESULTS: Seven studies with a total of 172
      patients met the inclusion criteria. The mean patient age was 55.3 years, and 83%
      of patients were female patients. Preoperative and postoperative Lysholm scores
      were reported for all patients. After a mean follow-up period of 30.2 months, the
      Lysholm score increased from 52.4 preoperatively to 85.9 postoperatively. On
      conventional radiographs, 64 of 76 patients (84%) showed no progression of
      Kellgren-Lawrence grading. Magnetic resonance imaging showed no progression of
      cartilage degeneration in 84 of 103 patients (82%) and showed reduced medial
      meniscal extrusion in 34 of 61 patients (56%). On the basis of second-look
      arthroscopy and magnetic resonance imaging in 137 patients, the healing status
      was rated as complete in 62%, partial in 34%, and failed in 3%. Overall, the
      methodologic quality of the included studies was fair, with a mean modified
      Coleman Methodology Score of 63. CONCLUSIONS: ATPR significantly improves
      functional outcome scores and seems to prevent the progression of osteoarthritis
      in most patients, at least during a short-term follow-up. Complete healing of the
      repaired root and reduction of meniscal extrusion seem to be less predictable,
      being observed in only about 60% of patients. Conclusions about the progression
      of osteoarthritis and reduction of meniscal extrusion are limited by the small
      portion of patients undergoing specific evaluation (44% and 35% of the study
      group, respectively). LEVEL OF EVIDENCE: Level IV, systematic review of Level III
      and IV studies.

PMID- 25979688
TI  - A Computed Tomography Study of Gender Differences in Acetabular Version and
      Morphology: Implications for Femoroacetabular Impingement.
AB  - PURPOSE: To assess the prevalence of acetabular retroversion in a large
      population of patients with asymptomatic hips. Furthermore, we sought to identify
      gender differences in acetabular morphology to address the current thinking that
      retroversion and pincer-type femoroacetabular impingement (FAI) are more common
      in women. METHODS: We retrospectively reviewed morphologic features of acetabula
      from a consecutive series of trauma-protocol computed tomography scans of
      patients without pelvis injury. An automated algorithm determined the acetabular
      rim profile and center of the femoral head, normalized the frontal plane of the
      pelvis, and calculated version and coverage. We then compared male and female rim
      profiles, specifically focusing on version and acetabular wall coverage in the 1
      o'clock (anterosuperior), 2-o'clock (central), and 3-o'clock (inferior)
      positions. RESULTS: Of 1,088 patients in the database, 878 had complete data
      (i.e., age, ethnicity, and body mass index) and were therefore included in the
      final analysis. Of these, 34.3% were women and 65.7% were men. Mean global
      acetabular version was 19.1 degrees  for men and 22.2 degrees  for women (P <
      .001). Mean acetabular version for men and women was 15.5 degrees  and 18.3
      degrees , respectively, in the 1-o'clock position; 21.5 degrees  and 24.0 degrees
      , respectively, in the 2-o'clock position; and 20.2 degrees  and 24.3 degrees ,
      respectively, in the 3-o'clock position (P < .001 for all 3). True retroversion
      (<0 degrees ) was observed only in the 1-o'clock position. The prevalence of true
      acetabular retroversion in the 1-o'clock position for men and women was 4.3% and
      3%, respectively (P = .36). CONCLUSIONS: Mean global and focal acetabular
      anteversion was greater in women, and the prevalence of focal cephalad
      retroversion in the 1-o'clock position was not significantly different compared
      with men. Acetabular retroversion and anterior overcoverage are not more
      prevalent in women in the anterosuperior acetabulum, where femoroacetabular
      impingement most commonly occurs. LEVEL OF EVIDENCE: Level III, diagnostic study.

PMID- 25979689
TI  - Treatment with hydrogen molecule attenuates cardiac dysfunction in streptozotocin
      induced diabetic mice.
AB  - INTRODUCTION: Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic
      patients, is one of the major causes of heart failure. The aim of present study
      was to investigate the therapeutic effect of hydrogen molecule on streptozotocin
      induced diabetic cardiomyopathy in mice. METHODS: Diabetes was induced in adult
      male mice by consecutive peritoneal injection of streptozotocin (50 mg/kg/day)
      for 5 days. Then, they were treated with hydrogen water (1.3+/-0.2 mg/l) for 8
      weeks (four groups, n=83-88 in each group). RESULTS: Although treatment of
      diabetic mice with hydrogen water did not significantly affect blood glucose
      level, it significantly attenuated cardiac hypertrophy and reduced expression of
      atrial natriuretic factor and beta-myosin heavy chain; it alleviated cardiac
      fibrosis and reduced expression of collagen I and III, transforming growth factor
      beta, alpha-smooth muscle actin, and osteopontin; it reduced cardiac caspase-3
      activity and ratio of bax/bcl-2. Importantly, hydrogen water treatment improved
      cardiac function in streptozotocin-diabetic mice. Furthermore, it was found that
      hydrogen water treatment abated oxidative stress, suppressed inflammation, and
      attenuated endoplasmic reticulum stress in the hearts of streptozotocin-diabetic
      mice. In addition, hydrogen water treatment suppressed activation of Jun NH2
      terminal kinase and p38 mitogen activated protein kinase signaling and nuclear
      factor kappaB signaling in the hearts of streptozotocin-diabetic mice.
      CONCLUSION: Treatment with hydrogen molecule attenuated cardiac dysfunction in
      streptozotocin-induced diabetic mice, which was independent of glycemic control.
      SUMMARY: Treatment with hydrogen molecule attenuated cardiac dysfunction in
      streptozotocin-induced type 1 diabetic mice. Molecular hydrogen could thus be
      envisaged as a nutritional countermeasure for diabetic cardiomyopathy.

PMID- 25979690
TI  - Tipping the balance both ways: drug resistance and virulence in Candida glabrata.
AB  - Among existing fungal pathogens, Candida glabrata is outstanding in its capacity
      to rapidly develop resistance to currently used antifungal agents. Resistance to
      the class of azoles, which are still widely used agents, varies in proportion
      (from 5 to 20%) depending on geographical area. Moreover, resistance to the class
      of echinocandins, which was introduced in the late 1990s, is rising in several
      institutions. The recent emergence of isolates with acquired resistance to both
      classes of agents is a major concern since alternative therapeutic options are
      scarce. Although considered less pathogenic than C. albicans, C. glabrata has
      still evolved specific virulence traits enabling its survival and propagation in
      colonized and infected hosts. Development of drug resistance is usually
      associated with fitness costs, and this notion is documented across several
      microbial species. Interestingly, azole resistance in C. glabrata has revealed
      the opposite. Experimental models of infection showed enhanced virulence of azole
      resistant isolates. Moreover, azole resistance could be associated with specific
      changes in adherence properties to epithelial cells or innate immunity cells
      (macrophages), both of which contribute to virulence changes. Here we will
      summarize the current knowledge on C. glabrata drug resistance and also discuss
      the consequences of drug resistance acquisition on the balance between C.
      glabrata and its hosts. 

PMID- 25979691
TI  - Functional pyruvate formate lyase pathway expressed with two different electron
      donors in Saccharomyces cerevisiae at aerobic growth.
AB  - Pyruvate formate lyase (PFL) is characterized as an enzyme functional at
      anaerobic conditions, since the radical in the enzyme's active form is sensitive
      to oxygen. In this study, PFL and its activating enzyme from Escherichia coli
      were expressed in a Saccharomyces cerevisiae strain lacking pyruvate
      decarboxylase and having a reduced glucose uptake rate due to a mutation in the
      transcriptional regulator Mth1, IMI076 (Pdc(-) MTH1-DeltaT ura3-52). PFL was
      expressed with two different electron donors, reduced ferredoxin or reduced
      flavodoxin, respectively, and it was found that the coexpression of either of
      these electron donors had a positive effect on growth under aerobic conditions,
      indicating increased activity of PFL. The positive effect on growth was
      manifested as a higher final biomass concentration and a significant increase in
      transcription of formate dehydrogenases. Among the two electron donors reduced
      flavodoxin was found to be a better electron donor than reduced ferredoxin. 

PMID- 25979692
TI  - Biological variation of established and novel biomarkers for atherosclerosis:
      Results from a prospective, parallel-group cohort study.
AB  - BACKGROUND: Biomarkers are a promising tool for the management of patients with
      atherosclerosis, but their variation is largely unknown. We assessed within
      subject and between-subject biological variation of biomarkers in peripheral
      artery disease (PAD) patients and healthy controls, and defined which biomarkers
      have a favorable variation profile for future studies. METHODS: Prospective,
      parallel-group cohort study, including 62 patients with stable PAD (79% men, 65+/
      7years) and 18 healthy control subjects (44% men, 57+/-7years). Blood samples
      were taken at baseline, and after 3-, 6-, and 12-months. We calculated within
      subject (CVI) and between-subject (CVG) coefficients of variation and intra-class
      correlation coefficient (ICC). RESULTS: Mean levels of D-dimer, hs-CRP, IL-6, IL
      8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in
      PAD patients than in healthy controls (P<=.05 for all). CVI and CVG of the
      different biomarkers varied considerably in both groups. An ICC>=0.5 (indicating
      moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10,
      MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy
      controls and for MMP-9, PAI-1 and sCD40L in PAD patients. CONCLUSIONS: Single
      biomarker measurements are of limited utility due to large within-subject
      variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP
      3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in
      PAD patients and a favorable variation profile making them most suitable for
      future studies.

PMID- 25979693
TI  - False positive in the measurement of thyroglobulin induced by rheumatoid factor.
AB  - BACKGROUND: We report a case of interference in thyroglobulin (Tg) measurement in
      a woman with differentiated thyroid cancer and rheumatoid arthritis history. Due
      to discordant Tg in relation to TSH concentrations and negative images, we
      investigated possible interference in the measurement of Tg. METHODS: During the
      follow-up we measured Tg by chemiluminescence (TgQL) using Immulite 2000
      immunoassay system. To investigate possible interference in Tg measurement, we
      made serial dilutions, re-testing of Tg by an alternative method:
      electrochemiluminescence, Cobas 6000 analyzer (TgEQL), recovery test of Tg and
      polyethylene glycol (PEG) 6000 precipitation. RESULTS: During the patient follow
      up, the TgQL ranged between <0.3 and 16.1ng/ml. In the evaluated serum samples
      very high titers of rheumatoid factor (RF) were found. When RF titers were
      lowered post PEG precipitation, Tg QL concentrations became undetectable.
      CONCLUSION: We describe an unusual case of interference in Tg assay due to RF.
      When disagreement among Tg concentrations, images and clinical features is
      observed, we suggest taking into account the evaluation of possible Tg
      interference to avoid unnecessary complementary exams and inappropriate
      treatment.

PMID- 25979694
TI  - Romantic relationships and psychological distress among adolescents: Moderating
      role of friendship closeness.
AB  - BACKGROUND: The formation of romantic relationships and friendships in
      adolescence is a defining milestone in the progression toward social maturity.
      Thus, examining adolescents' friendship and romantic experiences serves a vital
      role in understanding their psychological adjustment. AIMS: The main purposes of
      the current study were to examine (a) whether romantic involvement, romantic
      security, and friendship closeness were independently predictive of late
      adolescents' depression and loneliness, and (b) whether friendship closeness
      would moderate the negative effects of adolescents' lower degrees of romantic
      involvement and romantic security on depression and loneliness. METHOD: Data came
      from 12th grade adolescents (N = 110, 53 females) as well as their parents and a
      same-sex best friend. Adolescents reported on their romantic involvement,
      romantic security, and psychological distress. Parent reports of adolescents'
      depressive symptoms and friend reports of friendship closeness were also
      included. RESULTS: Higher degrees of romantic involvement and friendship
      closeness were related to lower degrees of loneliness. Higher degrees of romantic
      security were related to lower degrees of depression and loneliness. The effect
      of romantic involvement on depression and loneliness was moderated by friendship
      closeness. Also, the effect of romantic security on loneliness was moderated by
      friendship closeness. CONCLUSION: Future research should focus on the interactive
      roles that friendships and romantic relationships play in the emergence of
      psychopathology during adolescence.

PMID- 25979695
TI  - Immunotherapy of oneiric stupor in Morvan syndrome: Efficacy documented by
      actigraphy.

PMID- 25979696
TI  - Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22
      patients.
AB  - OBJECTIVE: We report the clinical features, comorbidities, and outcome of 22
      newly identified patients with antibodies to the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor (AMPAR). METHODS: This was a retrospective
      review of patients diagnosed between May 2009 and March 2014. Immunologic
      techniques have been reported previously. RESULTS: Patients' median age was 62
      years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) patients
      presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic
      dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by
      motor deficits, and one with psychosis with bipolar features. Fourteen patients
      (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2
      ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7
      patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related
      and cell surface), all with neurologic symptoms or tumor reflecting the
      concurrent autoimmunity. Treatment and outcome were available from 21 patients
      (median follow-up 72 weeks, range 5-266): 5 had good response to immunotherapy
      and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5
      patients died; all had a tumor or additional paraneoplastic symptoms related to
      onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor
      outcome (p = 0.009). CONCLUSION: Anti-AMPAR encephalitis usually manifests as LE,
      can present with other symptoms or psychosis, and is paraneoplastic in 64% of
      cases. Complete and impressive neurologic improvement can occur, but most
      patients have partial recovery. Screening for a tumor and onconeuronal antibodies
      is important because their detection influences outcome.

PMID- 25979697
TI  - Anti-AMPA receptor encephalitis: The family of glutamatergic autoencephalitides
      further expands.

PMID- 25979698
TI  - Dynamics of brain iron levels in multiple sclerosis: A longitudinal 3T MRI study.
AB  - OBJECTIVE: We investigated longitudinal changes in iron concentration in the
      subcortical gray matter (caudate nucleus, globus pallidus, putamen, thalamus) of
      patients with clinically isolated syndrome (CIS) and definite multiple sclerosis
      (MS) and their relation to clinical and other morphologic variables. METHODS: We
      followed 144 patients (76 CIS; median Expanded Disability Status Scale [EDSS] 1.0
      [interquartile range (IQR) 0.0-2.0]; 68 MS; median EDSS 2.0 [IQR 1.0-3.3])
      clinically and with 3T MRI over a median period of 2.9 (IQR 1.3-4.0) years. Iron
      concentration was determined by R2* relaxometry at baseline and last follow-up.
      RESULTS: At baseline, subcortical gray matter iron deposition was higher in MS
      compared to CIS. In CIS, R2* rates increased in the globus pallidus (p < 0.001),
      putamen (p < 0.001), and caudate nucleus (p < 0.001), whereas R2* rates in the
      thalamus decreased (p < 0.05). In MS, R2* rates increased in the putamen (p <
      0.05), remained stable in the globus pallidus and caudate nucleus, and decreased
      in the thalamus (p < 0.01). Changes in R2* relaxation rates were unrelated to
      changes in the volume of respective structures, of T2 lesion load, and of
      disability. CONCLUSIONS: Iron accumulation in the basal ganglia is more
      pronounced in the early than later phases of the disease and occurs independent
      from other morphologic brain changes. Short-term changes in iron concentration
      are not associated with disease activity or changes in disability.

PMID- 25979699
TI  - Trajectories of subcortical iron accumulation in MS.

PMID- 25979700
TI  - False localizing sign of cervico-thoracic CSF leak in spontaneous intracranial
      hypotension.
AB  - OBJECTIVE: Spontaneous spinal CSF leaks are an important cause of new-onset
      headaches. Such leaks are reported to be particularly common at the cervico
      thoracic junction. The authors undertook a study to determine the significance of
      these cervico-thoracic CSF leaks. METHODS: The patient population consisted of a
      consecutive group of 13 patients who underwent surgery for CSF leak repair based
      on CT myelography showing CSF extravasation at the cervico-thoracic junction but
      without any evidence of an underlying structural lesion. RESULTS: The mean age of
      the 9 women and 4 men was 41.2 years. Extensive extrathecal longitudinal CSF
      collections were demonstrated in 11 patients. At surgery, small leaking arachnoid
      cysts were found in 2 patients. In the remaining 11 patients, no clear source of
      CSF leakage could be identified at surgery. Resolution of symptoms was achieved
      in both patients with leaking arachnoid cysts, but in only 3 of the 11 patients
      with negative intraoperative findings. Postoperative spinal imaging was performed
      in 9 of the 11 patients with negative intraoperative findings and showed
      persistence of the longitudinal intraspinal extradural CSF. Further imaging
      revealed the site of the CSF leak to be ventral to the thoracic spinal cord. Five
      of these patients underwent microsurgical repair of the ventral CSF leak with
      resolution of symptoms in all 5 patients. CONCLUSIONS: Cervico-thoracic
      extravasation of dye on myelography does not necessarily indicate the site of the
      CSF leak. Treatment directed at this site should not be expected to have a high
      probability of sustained improvement of symptoms.

PMID- 25979702
TI  - Biomarkers in Parkinson disease: It's time to combine.

PMID- 25979703
TI  - High Court rejects claim that a GP trainee's sentence was too lenient.

PMID- 25979701
TI  - CSF proteins and resting-state functional connectivity in Parkinson disease.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      disruption of MRI-measured resting-state functional connectivity (rs-fcMRI) brain
      networks and CSF levels of potentially pathogenic proteins that reflect brain
      pathology in Parkinson disease (PD). METHODS: PD participants without dementia (n
      = 43) and age-matched controls (n = 22) had lumbar punctures to measure CSF
      protein levels, Pittsburgh compound B (PiB)-PET imaging, and rs-fcMRI while off
      medication. Imaging analyses focused on 5 major resting-state networks as well as
      the striatum. RESULTS: Participants with PD had significantly reduced
      sensorimotor functional connectivity, which correlated with reduced CSF levels of
      alpha-synuclein. The PD group also had significantly stronger default mode
      network functional connectivity that did not correlate with CSF beta-amyloid
      (Abeta)42 or PiB uptake. In contrast, default mode network functional
      connectivity in the control group did correlate with CSF Abeta42 levels.
      Functional connectivity was similar between groups in the dorsal attention,
      control, and salience networks. CONCLUSION: These results suggest that abnormal
      alpha-synuclein accumulation, but not Abeta, contributes to the disruption of
      motor-related functional connectivity in PD. Furthermore, correlating CSF protein
      measures with the strength of resting-state networks provides a direct link
      between abnormal alpha-synuclein metabolism and disrupted brain function in PD.

PMID- 25979704
TI  - The canonical eIF4E isoform of C. elegans regulates growth, embryogenesis, and
      germline sex-determination.
AB  - eIF4E plays a conserved role in initiating protein synthesis, but with multiple
      eIF4E isoforms present in many organisms, these proteins also adopt specialized
      functions. Previous RNAi studies showed that ife-3, encoding the sole canonical
      eIF4E isoform of Caenorhabditis elegans, is essential for viability. Using ife-3
      gene mutations, we show here that it is maternal ife-3 function that is essential
      for embryogenesis, but ife-3 null progeny of heterozygous animals are viable. We
      find that zygotic ife-3 function promotes body growth and regulates germline
      development in hermaphrodite worms. Specifically, the normal transition from
      spermatogenesis to oogenesis in the hermaphrodite germline fails in ife-3
      mutants. This failure to switch is reversed by inhibiting expression of the key
      masculinizing gene, fem-3, suggesting ife-3 resembles a growing number of genes
      that promote the sperm/oocyte switch by acting genetically as upstream inhibitors
      of fem-3. 

PMID- 25979705
TI  - The insulator protein CTCF regulates Drosophila steroidogenesis.
AB  - The steroid hormone ecdysone is a central regulator of insect development. In
      this report we show that CTCF expression in the prothoracic gland is required for
      full transcriptional activation of the Halloween genes spookier, shadow and
      noppera-bo, which encode ecdysone biosynthetic enzymes, and for proper timing of
      ecdysone-responsive gene expression. Loss of CTCF results in delayed and less
      synchronized larval development that can only be rescued by feeding larvae with
      both, the steroid hormone 20-hydroxyecdysone and cholesterol. Moreover, CTCF
      knockdown in prothoracic gland cells leads to increased lipid accumulation. In
      conclusion, the insulator protein CTCF is required for Halloween gene expression
      and cholesterol homeostasis in ecdysone-producing cells controlling
      steroidogenesis. 

PMID- 25979706
TI  - Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis.
AB  - During embryonic development, hematopoietic cells develop by a process of
      endothelial-to hematopoietic transition of a specialized population of
      endothelial cells. These hemogenic endothelium (HE) cells in turn develop from a
      primitive population of FLK1(+) mesodermal cells. Endoglin (ENG) is an accessory
      TGF-beta receptor that is enriched on the surface of endothelial and
      hematopoietic stem cells and is also required for the normal development of
      hemogenic precursors. However, the functional role of ENG during the transition
      of FLK1(+) mesoderm to hematopoietic cells is ill defined. To address this we
      used a murine embryonic stem cell model that has been shown to mirror the
      temporal emergence of these cells in the embryo. We noted that FLK1(+) mesodermal
      cells expressing ENG generated fewer blast colony-forming cells but had increased
      hemogenic potential when compared with ENG non-expressing cells. TIE2(+)/CD117(+)
      HE cells expressing ENG also showed increased hemogenic potential compared with
      non-expressing cells. To evaluate whether high ENG expression accelerates
      hematopoiesis, we generated an inducible ENG expressing ES cell line and forced
      expression in FLK1(+) mesodermal or TIE2(+)/CD117(+) HE cells. High ENG
      expression at both stages accelerated the emergence of CD45(+) definitive
      hematopoietic cells. High ENG expression was associated with increased
      pSMAD2/eNOS expression and NO synthesis in hemogenic precursors. Inhibition of
      eNOS blunted the ENG induced increase in definitive hematopoiesis. Taken
      together, these data show that ENG potentiates the emergence of definitive
      hematopoietic cells by modulating TGF-beta/pSMAD2 signalling and increasing
      eNOS/NO synthesis. 

PMID- 25979707
TI  - Nodal signaling is required for mesodermal and ventral but not for dorsal fates
      in the indirect developing hemichordate, Ptychodera flava.
AB  - Nodal signaling plays crucial roles in vertebrate developmental processes such as
      endoderm and mesoderm formation, and axial patterning events along the
      anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an
      essential role in the establishment of the dorsoventral axis and left-right
      asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal
      signaling appears to be involved only in establishing left-right asymmetry.
      Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the
      dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well
      as anteroposterior patterning in chordates. Hemichordata, together with
      echinoderms, represent the sister taxon to chordates. In this study, we analyze
      the role of Nodal signaling in the indirect developing hemichordate Ptychodera
      flava. In particular, we show that during gastrulation nodal transcripts are
      detected in a ring of cells at the vegetal pole that gives rise to endomesoderm
      and in the ventral ectoderm at later stages of development. Inhibition of Nodal
      function disrupts dorsoventral fates and also blocks formation of the larval
      mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical
      and ventral gene expression is affected while the dorsal side appears to be
      patterned correctly. Taken together, this study suggests that the co-option of
      Nodal signaling in mesoderm formation and potentially in anteroposterior
      patterning has occurred prior to the emergence of chordates and that Nodal
      signaling on the ventral side is uncoupled from BMP signaling on the dorsal side,
      representing a major difference from the molecular mechanisms of dorsoventral
      patterning events in echinoderms. 

PMID- 25979708
TI  - BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during
      spermatogenesis.
AB  - Meiosis is precisely regulated by the factors involved in DNA damage response in
      somatic cells. Among them, phosphorylation of H2AX on Serine 139 (gammaH2AX) is
      an essential signal for the silencing of unsynapsed sex chromosomes during male
      meiosis. However, it remains unknown how adjacent H2AX phosphorylation on
      Tyrosine 142 (pTyr142) is regulated in meiosis. Here we investigate the meiotic
      functions of BAZ1B (WSTF), the only known Tyr142 kinase in somatic cells, using
      mice possessing a conditional deletion of BAZ1B. Although BAZ1B deletion causes
      ectopic gammaH2AX signals on synapsed autosomes during the early pachytene stage,
      BAZ1B is dispensable for fertility and critical events during spermatogenesis.
      BAZ1B deletion does not alter events on unsynapsed axes and pericentric
      heterochromatin formation. Furthermore, BAZ1B is dispensable for localization of
      the ATP-dependent chromatin remodeling protein SMARCA5 (SNF2h) during
      spermatogenesis despite the complex formation between BAZ1B and SMARCA5, known as
      the WICH complex, in somatic cells. Notably, pTyr142 is regulated independently
      of BAZ1B and is dephosphorylated on the sex chromosomes during meiosis in
      contrast with the presence of adjacent gammaH2AX. Dephosphorylation of pTyr142 is
      regulated by MDC1, a binding partner of gammaH2AX. These results reveal the
      distinct regulation of two adjacent phosphorylation sites of H2AX during meiosis,
      and suggest that another kinase mediates Tyr142 phosphorylation. 

PMID- 25979709
TI  - Saponin-permeabilization is not a viable alternative to isolated mitochondria for
      assessing oxidative metabolism in hibernation.
AB  - Saponin permeabilization of tissue slices is increasingly popular for
      characterizing mitochondrial function largely because it is fast, easy, requires
      little tissue and leaves much of the cell intact. This technique is well
      described for mammalian muscle and brain, but not for liver. We sought to
      evaluate how saponin permeabilization reflects aspects of liver energy metabolism
      typically assessed in isolated mitochondria. We studied the ground squirrel
      (Ictidomys tridecemlineatus Mitchell), a hibernating mammal that shows profound
      and acute whole-animal metabolic suppression in the transition from winter
      euthermia to torpor. This reversible metabolic suppression is also reflected in
      the metabolism of isolated liver mitochondria. In this study we compared
      euthermic and torpid animals using saponin permeabilized tissue and mitochondria
      isolated from the same livers. As previously demonstrated, isolated mitochondria
      have state 3 respiration rates, fueled by succinate, that are suppressed by 60
      70% during torpor. This result holds whether respiration is standardized to
      mitochondrial protein, cytochrome a content or citrate synthase activity. In
      contrast, saponin-permeabilized liver tissue, show no such suppression in torpor.
      Neither citrate synthase activity nor VDAC content differ between torpor and
      euthermia, indicating that mitochondrial content remains constant in both
      permeabilized tissue and isolated mitochondria. In contrast succinate
      dehydrogenase activity is suppressed during torpor in isolated mitochondria, but
      not in permeabilized tissue. Mechanisms underlying metabolic suppression in
      torpor may have been reversed by the permeabilization process. As a result we
      cannot recommend saponin permeabilization for assessing liver mitochondrial
      function under conditions where acute changes in metabolism are known to occur. 

PMID- 25979710
TI  - Asymmetric cell division of granule neuron progenitors in the external granule
      layer of the mouse cerebellum.
AB  - The plane of division of granule neuron progenitors (GNPs) was analysed with
      respect to the pial surface in P0 to P14 cerebellum and the results showed that
      there was a significant bias towards the plane of cell division being parallel to
      pial surface across this developmental window. In addition, the distribution of
      beta-Catenin in anaphase cells was analysed, which showed that there was a
      significant asymmetry in the distribution of beta-Catenin in dividing GNPs.
      Further, inhibition of Sonic Hedgehog (Shh) signalling had an effect on plane of
      cell division. Asymmetric distribution of beta-Catenin was shown to occur towards
      the source of a localized extracellular cue. 

PMID- 25979711
TI  - Do Genetic Susceptibility Variants Associate with Disease Severity in Early
      Active Rheumatoid Arthritis?
AB  - OBJECTIVE: Genetic variants affect both the development and severity of
      rheumatoid arthritis (RA). Recent studies have expanded the number of RA
      susceptibility variants. We tested the hypothesis that these associated with
      disease severity in a clinical trial cohort of patients with early, active RA.
      METHODS: We evaluated 524 patients with RA enrolled in the Combination Anti
      Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility
      variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and
      amino acid polymorphisms in 6 HLA molecule positions - for their associations
      with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health
      Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and
      latent growth curve models. RESULTS: HLA variants were associated with joint
      destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002),
      and HLA-DRbeta1 amino acids histidine at position 13 (p = 0.0005) and valine at
      position 11 (p = 0.0012) significantly associated with radiological progression.
      This association was only significant in anticitrullinated protein antibody
      (ACPA)-positive patients, suggesting that while their effects were not mediated
      by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants
      did not associate with radiograph damage (assessed individually and cumulatively
      as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and
      rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24
      months. CONCLUSION: HLA susceptibility variants play an important role in
      determining radiological progression in early, active ACPA-positive RA. Genome
      wide and HLA-wide analyses across large populations are required to better
      characterize the genetic architecture of radiological progression in RA.

PMID- 25979712
TI  - Aggressive Therapy Reduces Disease Activity without Skeletal Damage Progression
      in Chronic Nonbacterial Osteomyelitis.
AB  - OBJECTIVE: To retrospectively assess changes in disease activity and skeletal
      damage in children with chronic nonbacterial osteomyelitis (CNO) after infliximab
      and methotrexate, with or without zoledronic acid or nonsteroidal
      antiinflammatory drug (NSAID) monotherapy, using a standardized magnetic
      resonance imaging (MRI) approach. METHODS: Treatment-related changes in clinical
      and MRI measures from aggressive therapy and NSAID monotherapy groups (n = 9 per
      group) were evaluated using nonparametric methods. RESULTS: Pain, physical
      function, physician global assessment, inflammatory markers, nonvertebral
      inflammatory lesion number, and maximum bone edema score all improved
      significantly with aggressive therapy (p < 0.03), whereas only the maximum soft
      tissue inflammation severity decreased (p = 0.02) with NSAID monotherapy.
      Vertebral deformities and physeal damage did not worsen in the aggressive therapy
      group but 1 in the NSAID group had worsening of growth plate damage. CONCLUSION:
      An aggressive treatment regimen in CNO improved clinical and imaging measures of
      disease activity without progression of skeletal damage.

PMID- 25979713
TI  - Whole-body Magnetic Resonance Imaging in Chronic Recurrent Multifocal
      Osteomyelitis: Clinical Longterm Assessment May Underestimate Activity.
AB  - OBJECTIVE: (1) To examine how many patients have clinically and/or radiologically
      active chronic recurrent multifocal osteomyelitis (CRMO) >= 10 years after first
      onset of symptoms, and (2) to compare clinical and whole-body magnetic resonance
      imaging (WB-MRI) findings. METHODS: Seventeen patients (82% women) who were
      diagnosed with childhood-onset CRMO at least 10 years (average 12) before
      reexamination were reevaluated. Patients completed a standardized questionnaire,
      and underwent clinical and laboratory investigation and WB-MRI. Clinical features
      were compared with imaging findings. RESULTS: Five patients were found to be in
      clinical and radiological remission. One of these patients demonstrated 1
      radiologically inactive lesion on WB-MRI. Four patients showed radiologically
      active lesions despite full clinical remission, 2 of them in 3 vertebral bodies.
      Spinal involvement in 6 patients (35%) caused vertebral compression fractures,
      vertebra plana, or vertebral hemifusion. Eight patients presented with ongoing
      clinical disease activity. When applying a CRMO activity score based on clinical
      and imaging findings, 2 patients were identified as having pain amplification.
      Overall, 22/55 known CRMO lesions were identified; 11 of them were radiologically
      active lesions. Additionally, 14 so far unknown clinically silent lesions were
      detected: 8 radiologically active lesions and 6 radiologically inactive lesions.
      CONCLUSION: CRMO activity on longterm followup might have been underestimated.
      Our study demonstrates that clinical remission does not necessarily mean
      radiological remission. We therefore propose that all patients with CRMO,
      including patients in clinical remission, require longterm clinical followup and
      should undergo evaluation with WB-MRI on a regular basis until radiological
      remission or a steady state of disease is achieved.

PMID- 25979714
TI  - Current Status of Efforts on Standardizing Magnetic Resonance Imaging of Juvenile
      Idiopathic Arthritis: Report from the OMERACT MRI in JIA Working Group and Health
      e-Child.
AB  - OBJECTIVE: To report on the progress of an ongoing research collaboration on
      magnetic resonance imaging (MRI) in juvenile idiopathic arthritis (JIA) and
      describe the proceedings of a meeting, held prior to Outcome Measures in
      Rheumatology (OMERACT) 12, bringing together the OMERACT MRI in JIA working group
      and the Health-e-Child radiology group. The goal of the meeting was to establish
      agreement on scoring definitions, locations, and scales for the assessment of MRI
      of patients with JIA for both large and small joints. METHODS: The collaborative
      work process included premeeting surveys, presentations, group discussions,
      consensus on scoring methods, pilot scoring, conjoint review, and discussion of a
      future research agenda. RESULTS: The meeting resulted in preliminary statements
      on the MR imaging protocol of the JIA knee and wrist and determination of the
      starting point for development of MRI scoring systems based on previous studies.
      It was also considered important to be descriptive rather than explanatory in the
      assessment of MRI in JIA (e.g., "thickening" instead of "hypertrophy"). Further,
      the group agreed that well-designed calibration sessions were warranted before
      any future scoring exercises were conducted. CONCLUSION: The combined efforts of
      the OMERACT MRI in JIA working group and Health-e-Child included the assessment
      of currently available material in the literature and determination of the basis
      from which to start the development of MRI scoring systems for both the knee and
      wrist. The future research agenda for the knee and wrist will include
      establishment of MRI scoring systems, an atlas of MR imaging in healthy children,
      and MRI protocol requisites.

PMID- 25979715
TI  - Magnetic Resonance Imaging in Hand Osteoarthritis: Intraobserver Reliability and
      Criterion Validity for Clinical and Structural Characteristics.
AB  - OBJECTIVE: To investigate criterion validity and intraobserver reliability of
      magnetic resonance imaging (MRI) in hand osteoarthritis (HOA). METHODS: In 16
      patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI
      scans with gadolinium-chelate administration of right second to fifth distal
      interphalangeal/proximal interphalangeal joints were scored according to the Oslo
      HOA scoring method for synovial thickening, bone marrow lesions (BML),
      osteophytes, joint space narrowing (JSN), and erosions (grade 0-3). Ultrasound
      (US) was scored for synovial thickening and osteophytes, radiographs for
      osteophytes and JSN (Osteoarthritis Research Society International score), and
      anatomical phases (Verbruggen-Veys score). Pain was assessed during physical
      examination. Correlations of MRI with US and radiographic features were assessed
      with generalizability theory. With generalized estimating equations analyses, MRI
      features were associated with pain, adjusting for confounding. RESULTS: Forty
      three percent, 27%, 77%, and 61% of joints had synovial thickening
      (moderate/severe), BML, osteophytes, and erosions on MRI, respectively.
      Intraobserver reliability, assessed in 6 patients, was good (ICC 0.77-1.00).
      Correlations between osteophytes, JSN, and erosions on radiographs and MRI were
      moderate, substantial, and fair (ICC 0.53, 0.68, and 0.32, respectively); MRI
      showed more lesions than radiography. Correlation between synovial thickening and
      osteophytes on MRI and US was moderate (ICC 0.43 and 0.49, respectively). MRI was
      more sensitive for synovial thickening, US for osteophytes. Pain was associated
      with moderate/severe synovial thickening (adjusted OR 2.4, 95% CI 1.06-5.5),
      collateral ligaments (4.2, 2.2-8.3), BML (3.5, 1.6-7.7), erosions (4.5, 1.7
      12.2), and osteophytes (2.4, 1.1-5.2). CONCLUSION: MRI is a reliable and valid
      method to assess inflammatory and structural features in HOA. It gives additional
      information over radiographs and US.

PMID- 25979716
TI  - Fibromyalgia and the Risk of a Subsequent Motor Vehicle Crash.
AB  - OBJECTIVE: Motor vehicle crashes are a widespread contributor to mortality and
      morbidity, sometimes related to medically unfit motorists. We tested whether
      patients diagnosed with fibromyalgia (FM) have an increased risk of a subsequent
      serious motor vehicle crash. METHODS: We conducted a population-based self
      matched longitudinal cohort analysis to estimate the incidence rate ratio of
      crashes among patients diagnosed with FM relative to the population norm in
      Ontario, Canada. We included adults diagnosed from April 1, 2006, to March 31,
      2012, excluding individuals younger than 18 years, living outside Ontario,
      lacking valid identifiers, or having only a single visit for the diagnosis. The
      primary outcome was an emergency department visit as a driver involved in a motor
      vehicle crash. RESULTS: The patients (n = 137,631) accounted for 738 crashes
      during the first year of followup after diagnosis, equal to an incidence rate
      ratio of 2.44 compared with the population norm (95% CI 2.27-2.63, p < 0.001).
      The crash rate was more than twice the population norm for those with a new or a
      persistent diagnosis. The increased risk included patients with diverse
      characteristics, approached the rate observed among other patients diagnosed with
      alcoholism, and was mitigated among those who received dedicated FM care or a
      physician warning for driving safety. CONCLUSION: A diagnosis of FM is associated
      with an increased risk of a subsequent motor vehicle crash that might justify
      medical interventions for traffic safety.

PMID- 25979717
TI  - 70th Annual Meeting of the Canadian Rheumatology Association, Quebec City,
      Quebec, Canada, February 4-7, 2015.
AB  - The 70th Annual Meeting of The Canadian Rheumatology Association (CRA) was held
      at the Fairmont Chateau Frontenac, Quebec City, Quebec, Canada, February 4-7,
      2015. The program consisted of presentations covering original research,
      symposia, awards, and lectures. Highlights of the meeting include 2015 Award
      Winners: Distinguished Rheumatologist Award: Carter Thorne; Distinguished
      Investigator Award: Hani El-Gabalawy; Teacher-Educator Award: Andrew E. Thompson;
      Young Investigator Award: Sindhu Johnson; Summer Studentship Mentor Award: Lori
      Albert; Innovation in Education Award: Henry Averns; Best Abstract for Basic
      Science Research by a Trainee: Sina Rusta-Sallehy; Best Abstract for Research by
      an Undergraduate Student: Tristan Kerr; Best Abstract for Research by a
      Rheumatology Resident: Claire Barber; Best Poster by a Medical Student: Dennis
      Wong; Best Poster by a Post-Graduate Resident: Zainab Alabdurubalnabi; CRA/ARF
      Best Epidemiology/Health Services Research Award: Evelyn Vinet; CRA/ARF Best
      Clinical Research Award: Glen Hazelwood; CRA/ARF Best Basic Science Research
      Award: Carolina Landolt-Marticorena; Ian Watson Award for Best Abstract for SLE
      Research by a Trainee: Ripneet Puar; Phil Rosen Award for Best Abstract for
      Clinical or Epidemiology Research by a Trainee: Liam O'Neil.

PMID- 25979718
TI  - Participation in Leisure Activities among Canadian Children with Arthritis:
      Results from a National Representative Sample.
AB  - OBJECTIVE: To describe the level of participation in leisure activities among
      children and youth with arthritis, as well as to identify the sociodemographic
      (age, sex, family income), disease-related (functional limitations, disease
      duration, pain, medication use, child's need for assistance), and contextual
      factors (use of rehabilitation services, proximity of local recreation
      facilities, cost of activities) that may be associated. METHODS: Data from the
      Participation and Activity Limitation Survey (PALS) 2006, a Canadian postcensus
      survey, was analyzed. Bivariate and multivariable linear regression analyses were
      applied to examine the associations between the sample's level of participation
      in leisure activities, and sociodemographic, disease-related, and contextual
      characteristics. RESULTS: In Canada in 2006, an estimated 4350 children ranging
      in age from 5 to 14 years were living with arthritis. Fifty-six percent of
      parents reported that arthritis restricted their child's participation in leisure
      activities. Bivariate analysis showed that the availability of local recreational
      facilities, the affordability of activities, and the child not requiring any
      assistance were all associated (modified Bonferroni correction alpha < 0.005)
      with greater participation in various types of leisure activities. Multiple
      linear regressions showed that higher family income (beta 0.47, 95% CI 0.09,
      0.85) and greater perceived pain (beta 0.59, 95% CI 0.07, 1.10) were positively
      associated with involvement in informal leisure. CONCLUSION: Our findings
      underline the importance of considering contextual factors in developing
      treatment plans aimed at improving participation in leisure activities among
      children with arthritis. Future longitudinal studies targeting children living
      with arthritis could provide pertinent information on participation over
      fluctuations in disease status.

PMID- 25979719
TI  - Optimal Strategies for Reporting Pain in Clinical Trials and Systematic Reviews:
      Recommendations from an OMERACT 12 Workshop.
AB  - OBJECTIVE: Pain is a patient-important outcome, but current reporting in
      randomized controlled trials and systematic reviews is often suboptimal, impeding
      clinical interpretation and decision making. METHODS: A working group at the 2014
      Outcome Measures in Rheumatology (OMERACT 12) was convened to provide guidance
      for reporting treatment effects regarding pain for individual studies and
      systematic reviews. RESULTS: For individual trials, authors should report, in
      addition to mean change, the proportion of patients achieving 1 or more
      thresholds of improvement from baseline pain (e.g., >= 20%, >= 30%, >= 50%),
      achievement of a desirable pain state (e.g., no worse than mild pain), and/or a
      combination of change and state. Effects on pain should be accompanied by other
      patient-important outcomes to facilitate interpretation. When pooling data for
      metaanalysis, authors should consider converting all continuous measures for pain
      to a 100 mm visual analog scale (VAS) for pain and use the established, minimally
      important difference (MID) of 10 mm, and the conventionally used, appreciably
      important differences of 20 mm, 30 mm, and 50 mm, to facilitate interpretation.
      Effects <= 0.5 units suggest a small or very small effect. To further increase
      interpretability, the pooled estimate on the VAS should also be transformed to a
      binary outcome and expressed as a relative risk and risk difference. This
      transformation can be achieved by calculating the probability of experiencing a
      treatment effect greater than the MID and the thresholds for appreciably
      important differences in pain reduction in the control and intervention groups.
      CONCLUSION: Presentation of relative effects regarding pain will facilitate
      interpretation of treatment effects.

PMID- 25979720
TI  - Circulating Angiogenic Factors and the Risk of Preeclampsia in Systemic Lupus
      Erythematosus Pregnancies.
AB  - OBJECTIVE: To investigate whether angiogenic factors are associated with risk of
      developing preeclampsia in pregnant women with systemic lupus erythematosus
      (SLE). METHODS: We performed a nested case-control study within a cohort of SLE
      women with singleton pregnancies. The study included 42 patients with SLE who
      eventually developed preeclampsia and 75 normal SLE pregnancies. Serum samples
      were collected at 4-week intervals (from weeks 12 to 36). Serum samples were
      analyzed for soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor
      (PlGF), and soluble endoglin (sEng). RESULTS: Women destined to develop
      preeclampsia had lower PlGF levels and higher sFlt-1 and sEng levels, and a
      higher sFlt-1/PlGF ratio than normal pregnancies. These changes became
      significant at 12 weeks in patients destined to develop either early onset (< 34
      weeks, p <= 0.003) or late-onset preeclampsia (>= 34 weeks, p <= 0.02). The risk
      to develop preeclampsia was higher among patients with PlGF concentration values
      in the lowest quartile or with sFlt-1 and sEng levels, and sFlt-1/PlGF ratio, in
      the highest quartile of the normal SLE pregnancies distribution. The OR were
      higher and appeared earlier in patients destined to develop early onset
      preeclampsia (OR >= 16.2, from Week 12 onward) than in patients who presented
      preeclampsia later (OR >= 8.9, from Week 24 onward). CONCLUSION: Changes in
      circulating concentrations of sFlt-1, PlGF, sEng, and the sFlt-1/PlGF ratio
      precede the onset of preeclampsia in SLE pregnancies. The risk profile of
      circulating angiogenic factors for developing preeclampsia distinctly evolves
      depending on whether this condition is manifested earlier or later.

PMID- 25979721
TI  - Risk of Psychiatric Disorders Following Primary Sjogren Syndrome: A Nationwide
      Population-based Retrospective Cohort Study.
AB  - OBJECTIVE: Primary Sjogren syndrome (pSS) is a chronic autoimmune disease. A
      clear temporal causal relationship between pSS and psychiatric disorders has not
      been well established. We used a nationwide population-based retrospective cohort
      study to explore the relationship between pSS and the subsequent development of
      psychiatric disorders. METHODS: We identified subjects who were newly diagnosed
      with pSS between January 1, 2000, and December 31, 2008, in the Taiwan National
      Health Insurance (NHI) Research Database. A comparison cohort was constructed for
      patients without pSS. There were 2686 patients with pSS and 10,744 matched
      controls observed until diagnosed with psychiatric disorders or until death,
      withdrawal from the NHI system, or December 31, 2009. The Institutional Review
      Board of Taipei Veterans General Hospital approved this study (2012-12-013BC).
      RESULTS: The adjusted HR of depressive disorder, anxiety disorder, and sleep
      disorder in subjects with pSS were significantly higher at 1.829, 1.856, and
      1.967 than those of the controls during the followup. We found that pSS might
      increase the risk of subsequent newly diagnosed depressive disorder, anxiety
      disorder, and sleep disorder that may impair life quality. CONCLUSION: Our
      findings highlight the need for psychiatric evaluation and intervention for
      patients with pSS.

PMID- 25979722
TI  - Intrarenal and Urinary Th9 and Th22 Cytokine Gene Expression in Lupus Nephritis.
AB  - OBJECTIVE: We studied the urinary sediment mRNA level of Th9- and Th22-related
      cytokines in patients with systemic lupus erythematosus (SLE). METHODS: We
      quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their
      corresponding transcription factors in 73 patients with active lupus nephritis,
      13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects.
      RESULTS: There was no detectable IL-9 mRNA in all samples. Patients with
      proliferative lupus nephritis had significantly lower urinary IL-22 mRNA levels
      than those with nonproliferative nephritis (2.2 +/- 5.4 vs 8.6 +/- 20.0 copies, p
      = 0.019), and urinary IL-22 mRNA level inversely correlated with the histological
      activity index (r = -0.427, p < 0.0001). In contrast, patients with lupus
      nephritis had significantly higher urinary IL-10 mRNA levels than patients with
      HTN (7.8 +/- 18.5 vs 1.9 +/- 4.0 copies, p = 0.012), and urinary IL-10 mRNA
      levels correlated with its intrarenal mRNA levels (r = 0.337, p = 0.004) and SLE
      disease activity index (r = 0.277, p = 0.018). Urinary IL-10 mRNA level was
      significantly lower among patients who achieved complete remission than those
      with partial remission or no response (4.1 +/- 6.5 vs 14.1 +/- 28.0 copies, p =
      0.036). CONCLUSION: Urinary IL-22 mRNA level is decreased in patients with SLE
      with proliferative nephritis, while urinary IL-10 mRNA levels correlates with its
      intrarenal mRNA level and disease activity. Urinary IL-10 mRNA levels may also
      predict treatment response. These results suggest that urinary mRNA levels of IL
      10 and IL-22 might be used as biomarkers for assessing disease activity and risk
      stratification in lupus nephritis.

PMID- 25979723
TI  - Psoriatic Arthritis Mutilans: Characteristics and Natural Radiographic History.
AB  - OBJECTIVE: (1) To compare clinical characteristics of patients with psoriatic
      arthritis (PsA) with PsA mutilans (PAM) and without PAM, and (2) to determine the
      rate of PAM radiographic progression. METHODS: A retrospective cohort study was
      conducted of all patients with PsA attending a teaching hospital. The most recent
      hand and feet radiographs were screened for PAM. Serial radiographs (earliest to
      most recent) were quantitatively scored for osteolysis, erosion, joint space
      narrowing, and osteoproliferation. RESULTS: Out of the 610 cases, 36 PsA cases
      had PAM (5.9%). PAM cases were younger at diagnosis of PsA than non-PAM cases (p
      = 0.04), had more prevalent psoriatic nail dystrophy (OR 5.43, p < 0.001), and
      worse health assessment questionnaire score (1.25 vs 0.63, p < 0.04).
      Radiographic axial disease (OR 2.31, adjusted p = 0.03) and especially
      radiographic sacroiliitis (OR 2.99, adjusted p = 0.01) were more prevalent in
      PAM. PAM were more likely than non-PAM cases to have used a disease-modifying
      antirheumatic drug (DMARD; OR 16.36, p < 0.001). Out of 33 cases, 29 PAM cases
      had initiated a synthetic DMARD and 4/13 had initiated anti-tumor necrosis factor
      (anti-TNF) prior to first demonstration of PAM. A median 5 radiographs were
      scored for each PAM case (interquartile range 3-7). PAM progressed from
      monoarticular (60%) to polyarticular (80%) involvement. Osteolysis was initially
      rapid and progressive in the hands and feet, tapering later during disease
      course. Nail dystrophy predicted more severe osteolysis (p = 0.03). CONCLUSION:
      Compared with non-PAM cases, PAM cases have earlier age at PsA diagnosis, poorer
      function, more prevalent nail dystrophy, and more radiographic axial
      disease/sacroiliitis. The rate of osteolysis is higher in earlier disease, and
      more severe in those with nail dystrophy. DMARD and anti-TNF therapy appear not
      to prevent PAM occurrence.

PMID- 25979725
TI  - Health & Demographic Surveillance System Profile: The Ifakara Rural and Urban
      Health and Demographic Surveillance System (Ifakara HDSS).
AB  - The Ifakara Rural HDSS (125,000 people) was set up in 1996 for a trial of the
      effectiveness of social marketing of bed nets on morbidity and mortality of
      children aged under 5 years, whereas the Ifakara Urban HDSS (45,000 people) since
      2007 has provided demographic indicators for a typical small urban centre
      setting. Jointly they form the Ifakara HDSS (IHDSS), located in the Kilombero
      valley in south-east Tanzania. Socio-demographic data are collected twice a year.
      Current malaria work focuses on phase IV studies for antimalarials and on
      determinants of fine-scale variation of pathogen transmission risk, to inform
      malaria elimination strategies. The IHDSS is also used to describe the
      epidemiology and health system aspects of maternal, neonatal and child health and
      for intervention trials at individual and health systems levels. More recently,
      IHDSS researchers have studied epidemiology, health-seeking and national
      programme effectiveness for chronic health problems of adults and older people,
      including for HIV, tuberculosis and non-communicable diseases. A focus on
      understanding vulnerability and designing methods to enhance equity in access to
      services are cross-cutting themes in our work. Unrestricted access to core IHDSS
      data is in preparation, through INDEPTH iSHARE [www.indepth-ishare.org] and the
      IHI data portal [http://data.ihi.or.tz/index.php/catalog/central].

PMID- 25979726
TI  - Data Resource Profile: German Health Update (GEDA)--the health interview survey
      for adults in Germany.
AB  - The German Health Update (GEDA) study is one component of the recently
      established nationwide health monitoring system administered by the Robert Koch
      Institute. The repeated cross-sectional GEDA surveys aim to provide current data
      on health and disease, health determinants and time trends in health and
      morbidity in the adult population in Germany. This forms the basis for planning
      requirements and recommendations for public health policy.Between 2008 and 2013,
      three GEDA waves were carried out, involving a total of 62,606 computer-assisted
      telephone interviews with adults in Germany, living in private household, and
      reachable via landline.A core set of indicators was used in all GEDA waves to
      gather information on subjective health and health-related quality of life,
      chronic diseases, injuries, impairment to health and disabilities, mental health,
      health behaviours, social determinants, use of health services and socio
      demographic characteristics.The data from the GEDA surveys are provided for
      public use and epidemiological research. After submitting an application form,
      the data are accessible from:
      [http://www.rki.de/EN/Content/Health_Monitoring/Public_Use_Files/public_use_file_
      ode.htm].

PMID- 25979727
TI  - Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7
      valent pneumococcal conjugate vaccine introduction.
AB  - AIMS: This population-based, retrospective study quantified the rates of all
      cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008
      to 2009 and determined the proportions of cases caused by pneumococcal vaccine
      serotypes. METHODS: Data on patients with all-cause and pneumococcal pneumonia,
      meningitis and septicemia were obtained from the Norwegian Patient Registry,
      which collects hospitalization data from all Norwegian public hospitals based on
      International Classification of Diseases codes. Norwegian Patient Registry case
      records linked to the Norwegian Surveillance System for Communicable Diseases
      provided serotype data for invasive pneumococcal disease in patients with
      microbiological cultures. RESULTS: In 2008 and 2009, hospitalization rates were
      relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per
      1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia
      (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for
      International Classification of Diseases-10 diagnosed pneumococcal pneumonia
      (from 13.66 to 10.52 per 100,000), although these cases may be under-reported
      because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed
      pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed
      pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal
      disease rates were highest in younger children and older adults, peaking at ? 60
      years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes
      included in the 7-valent pneumococcal conjugate vaccine decreased substantially
      during the study period, with corresponding serotype replacement by non-7-valent
      pneumococcal conjugate vaccine serotypes. CONCLUSIONS: From 2008 to 2009,
      International Classification of Diseases-10 diagnosed pneumococcal pneumonia,
      meningitis and septicemia decreased in most age groups but remained greatest
      among subjects aged 0-1 and ? 60 years.

PMID- 25979728
TI  - Open aortic arch replacement in high-risk patients: the gold standard.
AB  - OBJECTIVES: Open total aortic arch replacement (TAR) in high-risk patients is
      considered by some to be associated with a prohibitively perioperative risk.
      Recent reports describe hybrid techniques to treat this group. We reviewed our
      outcomes of open surgery in a 'high-risk' group of patients. METHODS: All
      patients who underwent open TAR between 2000 and 2013 were identified from our
      prospectively maintained database. Patients comparable with the ones who
      underwent hybrid repair in previous studies (logistic EuroSCORE between 20 and 60
      without intervention on the aortic root or on the mitral/tricuspid valve) were
      selected for analysis. RESULTS: Fifty-eight patients were identified. Median
      logistic EuroSCORE was 27.4 (range 20-57) and median age was 76 years (34.5%
      male). There were 11 resternotomies (18.9%) and 20 procedures were
      urgent/emergency (34.5%). Preoperative comorbidities included chronic obstructive
      pulmonary disease (31%), coronary artery disease (22.4%), peripheral vascular
      disease (48.3%), previous stroke (5.2%), previous myocardial infarction (3.4%)
      and left ventricular dysfunction (12%). Concomitant procedures included aortic
      valve replacement/resuspension (58.7%), coronary artery bypass grafting (22.4%),
      open descending aorta replacement (10.3%) and frozen elephant trunk (19%).
      Overall in-hospital mortality, permanent stroke and spinal cord injury rate were
      6.9, 1.7 and 0%, respectively. There were no deaths or stroke in the elective
      group. One-year, 5-year and 10-year estimates of survival were 82.7, 70.0 and
      37.8%, respectively. CONCLUSIONS: Open TAR can be performed with low mortality
      and morbidity and excellent long-term results even in high-risk patients. Total
      endovascular repair may represent an option for patients not suitable for open
      surgery.

PMID- 25979724
TI  - Adult height, coronary heart disease and stroke: a multi-locus Mendelian
      randomization meta-analysis.
AB  - Background: We investigated causal effect of completed growth, measured by adult
      height, on coronary heart disease (CHD), stroke and cardiovascular traits, using
      instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We
      developed an allele score based on 69 single nucleotide polymorphisms (SNPs)
      associated with adult height, identified by the IBCCardioChip, and used it for IV
      analysis against cardiovascular risk factors and events in 21 studies and 60 028
      participants. IV analysis on CHD was supplemented by summary data from 180 height
      SNPs from the GIANT consortium and their corresponding CHD estimates derived from
      CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT
      CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD
      by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85
      to 0.95, respectively],which agrees with the estimate from the Emerging Risk
      Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis
      revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV
      analysis showed that a 6.5-cm increase in height resulted in lower levels of body
      mass index ( P  < 0.001), triglycerides ( P  < 0.001), non high-density (non-HDL)
      cholesterol ( P  < 0.001), C-reactive protein ( P  = 0.042), and systolic blood
      pressure ( P  = 0.064) and higher levels of forced expiratory volume in 1 s and
      forced vital capacity ( P  < 0.001 for both). Conclusions: Taller individuals
      have a lower risk of CHD with potential explanations being that taller people
      have a better lung function and lower levels of body mass index, cholesterol and
      blood pressure.

PMID- 25979729
TI  - Trends in use of genotypic resistance testing and frequency of major drug
      resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999
      2011.
AB  - BACKGROUND: Monitoring antiretroviral drug resistance can inform treatment
      recommendations; however, there are few such data from US patients before they
      initiate ART. METHODS: We analysed data from HIV Outpatient Study (HOPS)
      participants from nine US HIV clinics who were diagnosed with HIV infection
      during 1999-2011. Using the IAS-USA December 2010 guidelines, we assessed the
      frequency of major drug resistance mutations (mDRMs) related to antiretroviral
      agents in viral isolates from patients who underwent commercial genotypic testing
      (GT) for resistance before initiating ART. We employed general linear regression
      models to assess factors associated with having undergone GT, and then factors
      associated with having mDRM. RESULTS: Among 1531 eligible patients, 758 (49.5%)
      underwent GT before first ART, increasing from 15.5% in 1999-2002 to 75.9% in
      2009-11 (P < 0.001). GT was carried out a median of 1.2 months after the
      diagnosis of HIV. In adjusted regression analyses, patients with pre-ART CD4+ T
      lymphocyte counts >=200 cells/mm(3) or with HIV RNA levels >5.0 log10 copies/mL
      and those with a first HOPS visit in 2006 or later were significantly (P < 0.05)
      more likely to have undergone GT. Of the 758 patients, 114 (15.0%) had mDRMs;
      mutations relating to NRTIs, NNRTIs and PIs were present in 8.0%, 7.1% and 2.6%,
      respectively. There was no temporal change in the frequency of mDRM, and mDRMs
      were associated with an HIV RNA level <4.0 log10 copies/mL. CONCLUSIONS: During
      1999-2011, GT use among antiretroviral-naive patients became more common, but a
      quarter of patients in recent years remained untested. The frequency of mDRMs
      remained stable over time at about 15%.

PMID- 25979730
TI  - Visual monitoring of Cucumber mosaic virus infection in Nicotiana benthamiana
      following transmission by the aphid vector Myzus persicae.
AB  - The single-stranded, positive-sense and tripartite RNA virus Cucumber mosaic
      virus (CMV) was used in this study as a method for monitoring the initial stages
      of virus infection following aphid transmission. The RNA2 of CMV was modified to
      incorporate, in a variety of arrangements, an open reading frame (ORF) encoding
      an enhanced green fluorescent protein (eGFP). The phenotypes of five engineered
      RNA2s were tested in Nicotiana tabacum, Nicotiana clevelandii and Nicotiana
      benthamiana. Only one construct (F4), in which the 2b ORF was truncated at the 3'
      end and fused in-frame with the eGFP ORF, was able to systemically infect N.
      benthamiana plants, express eGFP and be transmitted by the aphid Myzus persicae.
      The utility of this construct was demonstrated following infection as early as
      one day post-transmission (dpt) continuing through to systemic infection.
      Comparisons of the inoculation sites in different petiole sections one to three
      dpt clearly showed that the onset of infection and eGFP expression always
      occurred in the epidermal or collenchymatous tissue just below the epidermis; an
      observation consistent with the rapid time frame characteristic of the non
      persistent mode of aphid transmission. 

PMID- 25979731
TI  - Potyviruses differ in their requirement for TOR signalling.
AB  - Potyviruses are important plant pathogens that rely on many plant cellular
      processes for successful infection. TOR (target of rapamycin) signalling is a key
      eukaryotic energy-signalling pathway controlling many cellular processes such as
      translation and autophagy. The dependence of potyviruses on active TOR signalling
      was examined. Arabidopsis lines downregulated for TOR by RNAi were challenged
      with the potyviruses watermelon mosaic virus (WMV) and turnip mosaic virus
      (TuMV). WMV accumulation was found to be severely altered while TuMV accumulation
      was only slightly delayed. In another approach, using AZD-8055, an active site
      inhibitor of the TOR kinase, WMV infection was found to be strongly affected.
      Moreover, AZD-8055 application can cure WMV infection. In contrast, TuMV
      infection was not affected by AZD-8055. This suggests that potyviruses have
      different cellular requirements for active plant TOR signalling. 

PMID- 25979732
TI  - Different functional sensitivity to mutation at intersubunit interfaces involved
      in consecutive stages of foot-and-mouth disease virus assembly.
AB  - Small spherical viruses are paradigms of supramolecular self-assembly.
      Identifying the specific structural determinants for virus assembly provides
      guidelines to develop new antiviral drugs or engineer modified viral particles
      for medical or technological applications. However, very few systematic studies
      have been carried out so far to identify those chemical groups at interfaces
      between virus capsid subunits that are important for viral assembly and function.
      Foot-and-mouth disease virus (FMDV) and other picornaviruses are assembled in a
      stepwise process in which different protein-protein interfaces are formed: 5
      protomeric subunits oligomerize to form a pentameric intermediate, and 12 of
      these stable pentameric building blocks associate to form a labile capsid. In
      this study, a systematic mutational analysis revealed that very few amino acid
      side chains involved in substantial interactions between protomers within each
      pentamer are individually required for virus infectivity. This result contrasts
      sharply with the previous finding that most amino acid side chains involved in
      interactions between pentamers during the next assembly step are individually
      required for infectivity. The dramatic difference in sensitivity to single
      mutations between the two types of protein-protein interfaces in FMDV is
      discussed in terms of possible structural strategies for achieving self-assembly
      and genome uncoating in the face of diverse selective constraints. 

PMID- 25979733
TI  - Genetic manipulation of porcine epidemic diarrhoea virus recovered from a full
      length infectious cDNA clone.
AB  - Porcine epidemic diarrhoea virus (PEDV) causes acute diarrhoea and dehydration in
      swine of all ages, with significant mortality in neonatal pigs. The recent rise
      of PEDV outbreaks in Asia and North America warrants an urgent search for
      effective vaccines. However, PEDV vaccine research has been hampered by
      difficulties in isolating and propagating the virus in mammalian cells, thereby
      complicating the recovery of infectious PEDV using a full-length infectious
      clone. Here, we engineered VeroE6 cells to stably express porcine aminopeptidase
      N (pAPN) and used them as a platform to obtain a high-growth variant of PEDV,
      termed PEDVAVCT12. Subsequently, the full-length cDNA clone was constructed by
      assembling contiguous cDNA fragments encompassing the complete genome of
      PEDVAVCT12 in a bacterial artificial chromosome. Infectious PEDV could be
      recovered, and the rescued virus displayed phenotypic properties identical to the
      parental virus. Interestingly, we found that PEDVAVCT12 contained a C-terminal
      deletion of the spike gene, resulting in disruption of the ORF3 start codon. When
      a functional ORF3 gene was restored, the recombinant virus could not be rescued,
      suggesting that ORF3 could suppress PEDV replication in vitro. In addition, a
      high-growth and genetically stable recombinant PEDV expressing a foreign protein
      could be rescued by replacing the ORF3 gene with the mCherry gene. Together, the
      results of this study provide a means to generate genetically defined PEDV as a
      promising vaccine candidate. 

PMID- 25979734
TI  - Attribution of mental illness to work: a Delphi study.
AB  - BACKGROUND: Clinicians may be asked whether mental ill-health has been caused by
      work but there is no guidance on how this judgement should be made. AIMS: To seek
      a consensus on the factors that should be considered and how they should be
      sought when attributing mental ill-health to work. METHODS: A three-round Delphi
      study involving expert academics, occupational physicians, psychiatrists and
      psychologists. We deemed consensus had been reached when 66% or more of the
      experts were in agreement. RESULTS: Of 54 invited experts, 35 (65%) took part in
      the first round, 30 of these 35 (86%) in the second and 29 of these 30 (97%) in
      the final round. Consensus was reached for 11 workplace stressors: high job
      strain; effort-reward imbalance; major trauma; interpersonal conflict; inadequate
      support; role ambiguity; person-job mismatch; organizational injustice;
      organizational culture; work scheduling and threats to job security. Seven
      personal factors were identified as being important: previous mental illness;
      personality traits of neuroticism; adverse life events or social circumstances;
      resilience; a family history of mental illness and secondary gain. The worker,
      manager and co-workers were thought to be the most useful sources of workplace
      information. Consensus was reached for a definition of occupational mental
      illness but not for a threshold of work-relatedness. CONCLUSIONS: The attribution
      of mental ill-health to work is complex and involves the consideration of both
      workplace stressors and personal factors of vulnerability. Clinical consultation
      with an occupational physician who is familiar with the workplace is central to
      the process.

PMID- 25979735
TI  - Online reporting and assessing new occupational health risks in SIGNAAL.
AB  - BACKGROUND: Changes in work and working conditions continuously give rise to new
      work-related health risks. Without sufficient knowledge of these, opportunities
      for prevention and intervention may be missed. AIMS: To develop, implement and
      evaluate an online tool called SIGNAAL for reporting and assessment of new work
      related health risks by occupational health physicians and experts in the
      Netherlands and Belgium. METHODS: Development and implementation of SIGNAAL to
      allow both easy and sufficient detailed reporting by occupational health
      physicians and structured and transparent assessment by occupational health
      experts. A new work-related health risk is defined as a work-related disease due
      to specific exposure in a specific work setting not described in the literature
      before. RESULTS: The online reporting and assessment tool proved to be a feasible
      means of reporting possible new combinations of health problems and exposures in
      the work situation. Eleven of the 15 cases reported until October 2014 were fully
      assessed: one was an entirely new work-related disease, four were known but
      uncommon work-related diseases, five were known but new in the reported work
      situation and one was a well-known work-related disease. CONCLUSIONS: An online
      reporting system used in an occupational health setting can provide insight into
      new work-related health risks by creating a structured way to gather, report and
      assess new combinations of health problems and exposure in the workplace.

PMID- 25979736
TI  - BMI percentile-for-age overestimates adiposity in early compared with late
      maturing pubertal children.
AB  - OBJECTIVE: Early pubertal timing is consistently associated with increased BMI
      percentile-for-age in pubertal girls, while data in boys are more ambiguous.
      However, higher BMI percentile-for-age may be a result of the earlier puberty per
      se rather than vice versa. The aim was to evaluate markers of adiposity in
      relation to pubertal timing and reproductive hormone levels in healthy pubertal
      boys and girls. STUDY DESIGN: Population-based cross-sectional study (The
      Copenhagen Puberty Study). Eight-hundred and two healthy Caucasian children and
      adolescents (486 girls) aged 8.5-16.5 years participated. BMI and bioelectric
      impedance analyses (BIA) were used to estimate adiposity. Clinical pubertal
      markers (Tanner stages and testicular volume) were evaluated. LH, FSH, estradiol,
      testosterone, SHBG and IGF1 levels were determined by immunoassays. RESULTS: In
      all age groups, higher BMI (all 1 year age-groups, P <= 0.041) was found with
      early compared with late maturation, despite similar BIA-estimated body fat
      percentage (BIA-BF%). Neither BMI nor BIA-BF% differed for a given stage of
      maturation. BMI percentile-for-age and prevalence of overweight/obesity were
      higher in the early compared with late matured pubertal children (all P <=
      0.038), despite similar BIA-BF%. Pubertal girls with BIA-BF >29% had
      significantly lower LH and FSH levels compared with normal-weight girls (P <=
      0.041). CONCLUSIONS: Early maturational timing was not associated with higher
      adiposity for a given stage of puberty. Using BMI percentile-for-age
      overestimated the degree of adiposity in early pubertal compared with late
      pubertal children.

PMID- 25979737
TI  - Calibration system for radon EEC measurements.
AB  - The measurement of radon equivalent equilibrium concentration (EECRn) is very
      simple and quick technique for the estimation of radon progeny level in dwellings
      or working places. The most typical methods of EECRn measurements are alpha
      radiometry or alpha spectrometry. In such technique, the influence of alpha
      particle absorption in filters and filter effectiveness should be taken into
      account. In the authors' work, it is demonstrated that more precise and less
      complicated calibration of EECRn-measuring equipment can be conducted by the use
      of the gamma spectrometer as a reference measuring device. It was demonstrated
      that for this calibration technique systematic error does not exceed 3 %. The
      random error of (214)Bi activity measurements is in the range 3-6 %. In general,
      both these errors can be decreased. The measurements of EECRn by gamma
      spectrometry and improved alpha radiometry are in good agreement, but the
      systematic shift between average values can be observed. 

PMID- 25979738
TI  - Remedial activities effectiveness verification in tailing areas.
AB  - The complex radiological study of the basin of sludge from the uranium ore mining
      and preprocessing was done. Air kerma rates (including its spectral analysis) at
      the reference height of 1 m above ground over the whole area were measured and
      radiation fields mapped during two measuring campaigns (years 2009 and 2014). K,
      U and Th concentrations in sludge and concentrations in depth profiles (including
      radon concentration and radon exhalation rates) in selected points were
      determined using gamma spectrometry for in situ as well as laboratory samples
      measurement. Results were used for the analysis, design evaluation and
      verification of the efficiency of the remediation measures. Efficiency of the
      sludge basin covering by the inert material was modelled using MicroShield code. 

PMID- 25979739
TI  - Comparison of cosmic rays radiation detectors on-board commercial jet aircraft.
AB  - Aircrew members and passengers are exposed to increased rates of cosmic radiation
      on-board commercial jet aircraft. The annual effective doses of crew members
      often exceed limits for public, thus it is recommended to monitor them. In
      general, the doses are estimated via various computer codes and in some countries
      also verified by measurements. This paper describes a comparison of three cosmic
      rays detectors, namely of the (a) HAWK Tissue Equivalent Proportional Counter;
      (b) Liulin semiconductor energy deposit spectrometer and (c) TIMEPIX silicon
      semiconductor pixel detector, exposed to radiation fields on-board commercial
      Czech Airlines company jet aircraft. Measurements were performed during passenger
      flights from Prague to Madrid, Oslo, Tbilisi, Yekaterinburg and Almaty, and back
      in July and August 2011. For all flights, energy deposit spectra and absorbed
      doses are presented. Measured absorbed dose and dose equivalent are compared with
      the EPCARD code calculations. Finally, the advantages and disadvantages of all
      detectors are discussed. 

PMID- 25979741
TI  - On quasi-periodic variations of low-energy cosmic rays observed near earth.
AB  - Cosmic ray (CR) may partially, especially at high altitudes, contribute to the
      dosimetric characteristics. Along with irregular CR variations as Forbush
      decreases and solar particle events are, the quasi-periodic variations may be of
      some relevance too. A very short review (with references to original papers) of
      the present knowledge of various types of such variations is presented, namely
      (i) diurnal wave, (ii) ~27 d variability due to the solar rotation, (iii) Rieger
      type periodicity, and (iv) quasi-biennial oscillations as well as waves on longer
      time scales related to solar activity and to polarity of magnetic field of the
      Sun. Variability is illustrated in measurements of secondary CR on the ground
      including the high-altitude observations at Lomnicky stit.

PMID- 25979740
TI  - Modelling of nuclear power plant decommissioning financing.
AB  - Costs related to the decommissioning of nuclear power plants create a significant
      financial burden for nuclear power plant operators. This article discusses the
      various methodologies employed by selected European countries for financing of
      the liabilities related to the nuclear power plant decommissioning. The article
      also presents methodology of allocation of future decommissioning costs to the
      running costs of nuclear power plant in the form of fee imposed on each megawatt
      hour generated. The application of the methodology is presented in the form of a
      case study on a new nuclear power plant with installed capacity 1000 MW. 

PMID- 25979742
TI  - High Levels of Natural Radiation and Radon Areas.

PMID- 25979743
TI  - Assessment of levels of occupational exposure to workers in radiofrequency fields
      of two television stations in Accra, Ghana.
AB  - A survey of the radiofrequency (RF) radiation was undertaken within the premises
      of two television (TV) stations, TVA and TVB, in Accra, Ghana. The primary
      objective of this study was to determine the level of RF exposure to workers in
      the TV stations. A spectrum analyser, a bi-conical antenna (30-300 MHz) and a log
      periodic antenna (200 MHz-2.0 GHz) were used. Results obtained indicated that the
      wideband electric field strength levels recorded in this work vary between 0.006
      and 58.5 V m(-1) at TVA and between 0.007 and 28.5 V m(-1) at TVB. Compared with
      the results from TVB, TVA recorded relatively higher values in the 30-400 MHz
      range, whereas TVB produced relatively higher values in the 400 MHz-1.7 GHz
      range. Generally, results obtained were found to be below the occupational
      reference levels of the International Commission on Non-Ionizing Radiation
      Protection, but at some locations, the field intensity was 4.3 times higher than
      the reference levels for the general public. 

PMID- 25979744
TI  - Calibration of modified Liulin detector for cosmic radiation measurements on
      board aircraft.
AB  - The annual effective doses of aircrew members often exceed the limit of 1 mSv for
      the public due to the increased level of cosmic radiation at the flight
      altitudes, and thus, it is recommended to monitor them. Aircrew dosimetry is
      usually performed using special computer programs mostly based on results of
      Monte Carlo simulations. Contemporary, detectors are used mostly for validation
      of these computer codes, verification of effective dose calculations and for
      research purposes. One of such detectors is active silicon semiconductor
      deposited energy spectrometer Liulin. Output quantities of measurement with the
      Liulin detector are the absorbed dose in silicon D and the ambient dose
      equivalent H*(10); to determine it, two calibrations are necessary. The purpose
      of this work was to develop a calibration methodology that can be used to convert
      signal from the detector to D independently on calibration performed at Heavy Ion
      Medical Accelerator facility in Chiba, Japan. 

PMID- 25979745
TI  - Relative biological effectiveness of alpha particles at radon exposure.
AB  - The relative biological effectiveness (RBE) of alpha particles at radon exposure
      is estimated by comparison of radiation risks at external gamma exposure and
      radon exposure in different situations. For external gamma exposure, the BEIR VII
      model of radiation risk assessment was used. For occupational and indoor radon
      exposure, models such as BEIR VI, WISMUT, Tomasek's and combined miners
      population were considered. It was demonstrated that RBE values are strongly
      dependent on models of radiation risk assessment used for RBE calculation, sex of
      exposed peoples and age at the exposure. The average values of RBE in dependence
      on model of risk assessment choice are in the range from 1.5 to 12.0 for males
      and in the range from 0.34 to 2.7 for females. 

PMID- 25979746
TI  - Determining radioactive aerosol concentrations using a surface radioactive
      contamination measurement device.
AB  - For experiments with dispersed radioactive aerosols in a radon-aerosol chamber
      (RAC), it is desirable to know the activity of the radioactive aerosols applied
      in the RAC. A COLIBRI TTC survey metre with an SABG-15+ probe (Canberra, USA) was
      purchased for this purpose. The probe is designed for surface contamination
      measurements, and it is intended to measure the activity of aerosols deposited on
      the filters during experiments in the RAC. Since the probe is calibrated in a
      different geometry, its response in the authors' experimental geometry was
      simulated by a Monte Carlo method. The authors present a Monte Carlo model using
      MCNPX and an experimental verification of this probe model. 

PMID- 25979747
TI  - Radiation environment at aviation altitudes and in space.
AB  - On the Earth, protection from cosmic radiation is provided by the magnetosphere
      and the atmosphere, but the radiation exposure increases with increasing
      altitude. Aircrew and especially space crew members are therefore exposed to an
      increased level of ionising radiation. Dosimetry onboard aircraft and spacecraft
      is however complicated by the presence of neutrons and high linear energy
      transfer particles. Film and thermoluminescent dosimeters, routinely used for
      ground-based personnel, do not reliably cover the range of particle types and
      energies found in cosmic radiation. Further, the radiation field onboard aircraft
      and spacecraft is not constant; its intensity and composition change mainly with
      altitude, geomagnetic position and solar activity (marginally also with the
      aircraft/spacecraft type, number of people aboard, amount of fuel etc.). The
      European Union Council directive 96/29/Euroatom of 1996 specifies that aircrews
      that could receive dose of >1 mSv y(-1) must be evaluated. The dose evaluation is
      routinely performed by computer programs, e.g. CARI-6, EPCARD, SIEVERT, PCAire,
      JISCARD and AVIDOS. Such calculations should however be carefully verified and
      validated. Measurements of the radiation field in aircraft are thus of a great
      importance. A promising option is the long-term deployment of active detectors,
      e.g. silicon spectrometer Liulin, TEPC Hawk and pixel detector Timepix. Outside
      the Earth's protective atmosphere and magnetosphere, the environment is much
      harsher than at aviation altitudes. In addition to the exposure to high energetic
      ionising cosmic radiation, there are microgravity, lack of atmosphere,
      psychological and psychosocial components etc. The milieu is therefore very
      unfriendly for any living organism. In case of solar flares, exposures of
      spacecraft crews may even be lethal. In this paper, long-term measurements of the
      radiation environment onboard Czech aircraft performed with the Liulin since
      2001, as well as measurements and simulations of dose rates on and outside the
      International Space Station were presented. The measured and simulated results
      are discussed in the context of health impact. 

PMID- 25979748
TI  - Methodology for measurement in schools and kindergartens: experiences.
AB  - In more than 1500 schools and preschool facilities, long-term radon measurement
      was carried out in the last 3 y. The negative effect of thermal retrofitting on
      the resulting long-term radon averages is evident. In some of the facilities, low
      ventilation rates and correspondingly high radon levels were found, so it was
      recommended to change ventilation habits. However, some of the facilities had
      high radon levels due to its ingress from soil gas. Technical measures should be
      undertaken to reduce radon exposure in this case. The paper presents the long
      term experiences with the two-stage measurement methodology for investigation of
      radon levels in school and preschool facilities and its possible improvements. 

PMID- 25979749
TI  - A radiological survey of the Egrigoz granitoid, Western Anatolia/Turkey.
AB  - A radiological survey of the granitoid areas throughout Western Anatolia was
      conducted during 2007-14. As a part of this radiological survey, this article
      presents results obtained from Egrigoz pluton, which lies in the northeastern
      region of Western Anatolia. In the investigated area, the activity measurements
      of the natural gamma-emitting radionuclides ((226)Ra, (232)Th and (40)K) in the
      granitic rock samples and soils have been carried out by means of the NaI(Tl)
      gamma-ray spectrometry system. The activity concentrations of the relevant
      natural radionuclides in the granite samples appeared in the ranges as follows:
      (226)Ra, 28-95 Bq kg(-1); (232)Th, 50-122 Bq kg(-1) and (40)K, 782-1365 Bq kg(
      1), while the typical ranges of the (226)Ra, (232)Th and (40)K activities in the
      soil samples were found to be 7-184, 11-174 and 149-1622 Bq kg(-1), respectively.
      Based on the available data, the radiation hazard parameters associated with the
      surveyed rocks/soils are calculated. The corresponding absorbed dose rates in air
      from all those radionuclides were always much lower than 200 nGy h(-1) and did
      not exceed the typical range of worldwide average values noted in the UNSCEAR
      (2000) report. Furthermore, the data are also used for the mapping of the surface
      soil activity of natural radionuclides and the corresponding gamma dose rates of
      the surveyed area. 

PMID- 25979750
TI  - Estimating the dynamics and dependencies of accumulating mutations with
      applications to HIV drug resistance.
AB  - We introduce a new model called the observed time conjunctive Bayesian network
      (OT-CBN) that describes the accumulation of genetic events (mutations) under
      partial temporal ordering constraints. Unlike other CBN models, the OT-CBN model
      uses sampling time points of genotypes in addition to genotypes themselves to
      estimate model parameters. We developed an expectation-maximization algorithm to
      obtain approximate maximum likelihood estimates by accounting for this additional
      information. In a simulation study, we show that the OT-CBN model outperforms the
      continuous time CBN (CT-CBN) (Beerenwinkel and Sullivant, 2009. Markov models for
      accumulating mutations. Biometrika 96: (3), 645-661), which does not take into
      account individual sampling times for parameter estimation. We also show
      superiority of the OT-CBN model on several datasets of HIV drug resistance
      mutations extracted from the Swiss HIV Cohort Study database. 

PMID- 25979751
TI  - Rapid Acclimation Ability Mediated by Transcriptome Changes in Reef-Building
      Corals.
AB  - Population response to environmental variation involves adaptation, acclimation,
      or both. For long-lived organisms, acclimation likely generates a faster response
      but is only effective if the rates and limits of acclimation match the dynamics
      of local environmental variation. In coral reef habitats, heat stress from
      extreme ocean warming can occur over several weeks, resulting in symbiont
      expulsion and widespread coral death. However, transcriptome regulation during
      short-term acclimation is not well understood. We examined acclimation during a
      11-day experiment in the coral Acropora nana. We acclimated colonies to three
      regimes: ambient temperature (29  degrees C), increased stable temperature (31 
      degrees C), and variable temperature (29-33  degrees C), mimicking local heat
      stress conditions. Within 7-11 days, individuals acclimated to increased
      temperatures had higher tolerance to acute heat stress. Despite physiological
      changes, no gene expression changes occurred during acclimation before acute heat
      stress. However, we found strikingly different transcriptional responses to heat
      stress between acclimation treatments across 893 contigs. Across these contigs,
      corals acclimated to higher temperatures (31  degrees C or 29-33  degrees C)
      exhibited a muted stress response--the magnitude of expression change before and
      after heat stress was less than in 29  degrees C acclimated corals. Our results
      show that corals have a rapid phase of acclimation that substantially increases
      their heat resilience within 7 days and that alters their transcriptional
      response to heat stress. This is in addition to a previously observed longer term
      response, distinguishable by its shift in baseline expression, under nonstressful
      conditions. Such rapid acclimation may provide some protection for this species
      of coral against slow onset of warming ocean temperatures.

PMID- 25979752
TI  - Metagenome Skimming of Insect Specimen Pools: Potential for Comparative Genomics.
AB  - Metagenomic analyses are challenging in metazoans, but high-copy number and
      repeat regions can be assembled from low-coverage sequencing by "genome
      skimming," which is applied here as a new way of characterizing metagenomes
      obtained in an ecological or taxonomic context. Illumina shotgun sequencing on
      two pools of Coleoptera (beetles) of approximately 200 species each were
      assembled into tens of thousands of scaffolds. Repeated low-coverage sequencing
      recovered similar scaffold sets consistently, although approximately 70% of
      scaffolds could not be identified against existing genome databases. Identifiable
      scaffolds included mitochondrial DNA, conserved sequences with hits to expressed
      sequence tag and protein databases, and known repeat elements of high and low
      complexity, including numerous copies of rRNA and histone genes. Assemblies of
      histones captured a diversity of gene order and primary sequence in Coleoptera.
      Scaffolds with similarity to multiple sites in available coleopteran genome
      sequences for Dendroctonus and Tribolium revealed high specificity of scaffolds
      to either of these genomes, in particular for high-copy number repeats. Numerous
      "clusters" of scaffolds mapped to the same genomic site revealed intra- and/or
      intergenomic variation within a metagenome pool. In addition to effect of
      taxonomic composition of the metagenomes, the number of mapped scaffolds also
      revealed structural differences between the two reference genomes, although the
      significance of this striking finding remains unclear. Finally, apparently
      exogenous sequences were recovered, including potential food plants, fungal
      pathogens, and bacterial symbionts. The "metagenome skimming" approach is useful
      for capturing the genomic diversity of poorly studied, species-rich lineages and
      opens new prospects in environmental genomics. 

PMID- 25979753
TI  - EGFR and NF-kappaB: partners in cancer.
AB  - Oncogenic proteins cooperate to promote tumor development and progression by
      sustaining cell proliferation, survival and invasiveness. Constitutive epidermal
      growth factor receptor (EGFR) and nuclear factor kappab (NF-kappaB) activities
      are seen in multiple solid tumors and combine to provide oncogenic signals to
      cancer cells. Understanding how these oncogenic pathways are connected is
      crucial, given their role in intrinsic or acquired resistance to targeted
      anticancer therapies. We review molecular mechanisms by which both EGFR- and NF
      kappaB-dependent pathways establish positive loops to increase their oncogenic
      potential. We also describe how NF-kappaB promotes resistance to EGFR inhibitors.

PMID- 25979754
TI  - The genetics of lipid storage and human lipodystrophies.
AB  - Life depends on securing sufficient energy intake to enable growth, movement, and
      reproduction. Throughout evolution, lifeforms have struggled to ensure adequate
      energy intake, and this remains a major challenge for many species. Modern humans
      are particularly well adapted to store surplus energy efficiently, but they are
      considerably less well adapted for coping with sustained access to energy-dense
      food. We briefly review the evolution of adipocytes and the metabolic
      consequences of suboptimal energy storage, focusing on insights derived from rare
      human monogenic disorders. From the evidence presented, we argue that a mismatch
      between the capacity for nutrient storage and the burden of excess energy intake
      is an important factor in the development of some forms of human insulin
      resistance. 

PMID- 25979755
TI  - [Tangential excision for a longitudinal melanonychia].

PMID- 25979756
TI  - [Item 345 - UE 11 Acute enlarged red leg].

PMID- 25979758
TI  - The origins and evolution of dwarf males and habitat use in thoracican barnacles.
AB  - Barnacles are exceptional in having various sexual systems (androdioecy,
      hermaphroditism, dioecy) and with a high morphological diversity of males, though
      these are always minute (dwarf) compared to their female or hermaphrodite
      partners. For the first time, we use a multiple DNA marker-based phylogeny to
      elucidate the ancestral states and evolution of (1) dwarf males, (2) their
      morphology when present, (3) their attachment site on the partner, and (4)
      habitat use in thoracican barnacles. Our taxon sampling was especially rich in
      rare deep-sea Scalpelliformes and comprised species with diverse sexual systems
      and dwarf male morphologies. Within the thoracican barnacles dwarf male evolution
      is subject to extensive convergence, but always correlated to similar ecological
      conditions. Males evolved convergently at least four times from purely
      hermaphroditic ancestors, in each case correlated with the invasion into habitats
      with low mating group sizes. The independent evolution of dwarf males in these
      lineages dovetails with the males having different morphologies and occurring in
      several different locations on their sexual partner. 

PMID- 25979757
TI  - [Item 211 - UE 7 Purpura in children and adults].

PMID- 25979759
TI  - Effect of cytokine antibodies in the immunomodulation of inflammatory response
      and metabolic disorders induced by scorpion venom.
AB  - Androctonus australis hector (Aah) venom and its neurotoxins may affect the neuro
      endocrine immunological axis due to their binding to ionic channels of axonal
      membranes. This binding leads to the release of neurotransmitters and
      immunological mediators accompanied by pathophysiological effects. Although the
      hyperglycemia induced by scorpion venom is clearly established, the involved
      mediators in these deregulations are unknown. The strong relationship between
      inflammation and the wide variety of physiological processes can suggest that the
      activation of the inflammatory response and the massive release of IL-6 and TNF
      alpha release induced by the venom may induce hyperglycemia and various
      biological disorders. We therefore investigated in this study the contribution of
      IL-6 and TNF-alpha in the modulation of inflammatory response and metabolic
      disorder induced by Aah venom. Obtained results revealed that Aah venom induced
      inflammatory response characterized by significant increase of inflammatory cells
      in sera and tissues homogenates accompanied by hyperglycemia and
      hyperinsulinemia, suggesting that the venom induced insulin resistance. It also
      induced severe alterations in hepatic parenchyma associated to metabolic
      disorders and imbalanced redox status. Cytokine antagonists injected 30 min prior
      to Aah venom allowed a significant reduction of inflammatory biomarker and plasma
      glucose levels, they also prevented metabolic disorders, oxidative stress and
      hepatic tissue damage induced by Aah venom. In conclusion, IL-6 and TNF-alpha
      appear to play a crucial role in the inflammatory response, hyperglycemia and
      associated complications to glucose metabolism disorders (carbohydrate and fat
      metabolism disorders, oxidative stress and hepatic damage) observed following
      scorpion envenoming.

PMID- 25979760
TI  - Dietary soy isoflavone attenuated growth performance and intestinal barrier
      functions in weaned piglets challenged with lipopolysaccharide.
AB  - This study was conducted to investigate the protective roles of soy isoflavone in
      weaned pigs challenged with lipopolysaccharide (LPS). A total of 72 weaned
      piglets (14 days of age) were randomly allotted into either 0 (control group) or
      40 mg/kg soy isoflavone (ISO) supplementation group. On days 7 and 14, half of
      the pigs in each group were challenged with LPS. Soy isoflavone increased average
      daily gain (ADG) and average daily feed intake (ADFI) of piglets challenged with
      LPS at days 7-14 (P<0.05). The incidence of diarrhea and plasma concentrations of
      malondialdehyde (MDA) and endotoxin in piglets from LPS group were higher than
      those in control group (P<0.05). Soy isoflavone reduced the incidence of diarrhea
      and plasma concentrations of endotoxin in piglets challenged with LPS (P<0.05).
      LPS challenge decreased (P<0.05) mRNA abundances of beta-defensin 2 (pBD-2),
      mucin (MUC-4), zona occludens 1 (ZO-1), and occludin in jejunal mucosa of
      piglets, and soy isoflavone upregulated (P<0.05) mRNA abundances of ZO-1 and
      occludin in jejunal mucosa of piglets challenged with LPS. The present results
      demonstrated that both p38 and TLR4 pathways in jejunal mucosa of piglets were
      activated by LPS challenge (P<0.05), and soy isoflavone reduced their activations
      (P<0.05). Collectively, our results suggested that supplementation of soy
      isoflavone could partly attenuate the barrier-damaged effects of LPS and improve
      the intestinal barrier function of weaned piglets, at least partially by
      inhibiting activations of p38 and TLR4 dependent pathways induced by LPS. This
      study provides a potential usage of soy isoflavone for alleviating intestinal
      barrier damages of neonates and piglets.

PMID- 25979761
TI  - Nicotinic receptor-dependent and -independent effects of galantamine, an
      acetylcholinesterase inhibitor, on the non-neuronal acetylcholine system in C2C12
      cells.
AB  - We previously reported that satellite cells possess the ability to produce
      angiogenic factors, including fibroblast growth factor (FGF)-2 and vascular
      endothelial growth factor (VEGF) in vivo. However, whether C2C12 cells possess a
      non-neuronal cholinergic system (NNCS) or non-neuronal ACh (NNA) remains to be
      studied; therefore, we investigated the system using C2C12 cells and its
      regulatory mechanisms. C2C12 cells synthesized ACh, the level of which was
      comparable with that of cardiomyocytes, and the synthesis was augmented by the
      acetylcholinesterase inhibitor galantamine. The ChAT promoter activity was
      upregulated by nicotine or galantamine, partly through nicotinic receptors for
      both agents as well as through a non-nicotinic receptor pathway for galantamine.
      Further, VEGF secretion by C2C12 cells was also increased by nicotine or
      galantamine through nicotinic receptors as well as partly through non-nicotinic
      pathways in the case of galantamine. These results suggest that C2C12 cells are
      equipped with NNCS or NNA, which is positively regulated through nicotinic or non
      nicotinic pathways, particularly in the case of galantamine. These results
      provide a novel concept that myogenic cells expressing NNA can be a therapeutic
      target for regulating angiogenic factor synthesis. 

PMID- 25979762
TI  - Comparative analysis of methods to determine DNA methylation levels of a tumor
      related microRNA gene.
AB  - Quantifying levels of DNA methylation in tumors is a useful approach for the
      identification of potential tumor suppressors and to find biomarkers that can be
      used as prognostic or therapeutic indicators. In the current study, we compared
      three methods commonly used for quantifying DNA methylation-bisulfite
      pyrosequencing, quantitative methylation-specific PCR (Q-MSP), and MethyLight-by
      focusing on the CpG island of the gene encoding the microRNA-34b and microRNA-34c
      (miR-34b/c); aberrant regulation of this miR is associated with various human
      malignancies, including gastric cancer. Standard curve analysis using control DNA
      samples demonstrated the highest quantitative accuracy in Q-MSP analysis. We also
      carried out methylation analysis using gastric mucosa specimens obtained from
      gastric cancer patients. We found a high correlation between methylation levels
      determined by Q-MSP and those determined by MethyLight (R(2)=0.952), whereas the
      results of bisulfite pyrosequencing and the other two methods were less well
      correlated (R(2)=0.864 and R(2)=0.804 for Q-MSP and MethyLight, respectively).
      This may reflect possible PCR bias in the pyrosequencing technique, which we show
      can be corrected for by applying a cubic approximate equation to the original
      data. Thus, although results obtained by the different DNA methylation analysis
      techniques are largely comparable, an appropriate correction may be necessary for
      stringent comparison. 

PMID- 25979763
TI  - Ruthenium-106 plaque brachytherapy for uveal melanoma.
AB  - BACKGROUND: To report on local tumour control, eye preservation and visual
      outcome after ruthenium-106 brachytherapy for uveal melanoma. METHODS: Medical
      records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy
      between 1997 and 2012 at one single centre, were included. Primary outcome
      measures were local tumour control, eye preservation and visual outcome. The
      influence of patient, tumour and treatment parameters on outcome was analysed by
      time to event analysis and competing risk regression. RESULTS: The median overall
      follow-up was 37.9 months. Tumour control: recurrent tumour growth was observed
      in 17 patients. The estimated local tumour recurrence rate at 12, 24 and 48
      months after irradiation was 3%, 8.4% and 14.7%, respectively. The only
      significant risk factors for tumour recurrence were age (p=0.046) and reduced
      initial visual acuity (VA, p=0.045). No significant difference could be shown for
      tumour size or tumour category (T1-T2 vs T3-T4), and for any other tumour or
      treatment parameters (including combined transpupillary thermo-therapy (TTT)).Eye
      preservation: The likelihood of keeping the eye 12, 24 and 48 months after
      irradiation was 97.7%, 94.7% and 91.8%, respectively. Most significant risk
      factors for secondary enucleation were initial VA (p<0.001), tumour height
      (p=0.002) and tumour category (p=0.015). VISION: The chances of keeping VA of
      20/200 or better at 1, 2 and 5 years after treatment were 86.4%, 80.8% and 61.7%,
      respectively. Patients receiving sandwich-TTT showed significantly worse visual
      outcomes. CONCLUSIONS: Ruthenium-106 brachytherapy appears to be a useful
      treatment regarding tumour control, eye preservation and visual function. Adjunct
      sandwich therapy resulted in worse visual outcome.

PMID- 25979764
TI  - FGF2 alleviates PTSD symptoms in rats by restoring GLAST function in astrocytes
      via the JAK/STAT pathway.
AB  - In our previous study, we demonstrated that fibroblast growth factor 2 (FGF2)
      administration alleviated posttraumatic stress disorder (PTSD) symptoms via an
      "astrocyte-related" mechanism. We further investigated the changes in the
      astrocytic glutamate transporters GLAST and GLT-1 and in JAK/STAT3 signaling
      (which is involved in astrocyte activation and GLAST/GLT-1 function) in single
      prolonged stress (SPS) model rats. High-performance liquid chromatography (HPLC),
      Western blot and immunohistochemistry analyses revealed a significant SPS-induced
      increase in the concentration of glutamate in the cerebrospinal fluid and
      decrease in GLAST/GLT-1 expression and JAK/STAT3 signaling. Treatment with FGF2
      significantly alleviated GLAST/GLT-1 dysfunction, JAK/STAT3 signaling inhibition,
      and the behavioral abnormalities. The administration of the JAK/STAT pathway
      inhibitor AG490 blocked the effects of FGF2 on PTSD symptoms, astrocyte
      activation, and GLAST, but not GLT-1, expression in vivo and in vitro. Our
      findings suggest that astrocytic JAK/STAT signaling is associated with SPS
      induced GLAST dysfunction and that FGF2 protects against PTSD symptoms by
      restoring astrocytic glutamate uptake via the JAK/STAT signaling pathway. 

PMID- 25979766
TI  - Purinergic signaling in the immune system.
AB  - Extracellular ATP and its metabolite adenosine are increasingly recognized as key
      mediators of the immune response. Depending on the concentration, ATP may act as
      an immunostimulant or an immunodepressant, while adenosine is generally
      acknowledged to be a potent immunosupressor molecule. Signals delivered by
      extracellular ATP and adenosine are detected and transduced by P2 and P1
      receptors, respectively. Virtually all immune cells express P2 and P1 receptors,
      thus purinergic signaling affects all aspects of immunity and inflammation. This
      realization has prompted a burst of novel investigations aimed at the design and
      synthesis of P2- or P1-targeted drugs for the treatment of chronic inflammatory
      diseases and cancer. In this review we will summarize the most recent
      developments in this field. 

PMID- 25979765
TI  - D-aspartate dysregulation in Ddo(-/-) mice modulates phencyclidine-induced gene
      expression changes of postsynaptic density molecules in cortex and striatum.
AB  - N-methyl-D-aspartate receptor (NMDAR) hypofunction has been considered a key
      alteration in schizophrenia pathophysiology. Thus, several strategies aimed at
      enhancing glutamatergic transmission, included the introduction in therapy of D
      amino acids, such as D-serine and D-cycloserine augmentation, have been proposed
      to counteract difficult-to-treat symptoms or treatment-resistant forms of
      schizophrenia. Another D-amino acid, D-aspartate, has recently gained increasing
      interest for its role in NMDAR activation and has been found reduced in post
      mortem cortex of schizophrenia patients. NMDAR is the core of the postsynaptic
      density (PSD), a postsynaptic site involved in glutamate signaling and responsive
      to antipsychotic treatment. In this study, we investigated striatal and cortical
      gene expression of key PSD transcripts (i.e. Homer1a, Homer1b/c, and PSD-95) in
      mice with persistently elevated brain D-aspartate-levels, i.e. the D-aspartate
      oxidase knockout mice (Ddo(-/-)). These animal models were analyzed both in naive
      condition and after phencyclidine (PCP) treatment. Naive Ddo(-/-) mice showed
      decreased Homer1a expression in the prefrontal cortex, increased Homer1b/c
      expression in the striatum, and decreased PSD-95 expression in the striatum and
      in the cortex. Acute PCP treatment restored, and even potentiated, Homer1a
      expression in the prefrontal cortex of mutant mice, while it had limited effects
      on the other genes. These results suggest that persistently elevated D-aspartate,
      by enhancing NMDA transmission, may cause complex adaptive mechanisms affecting
      Homer1a, which in turn may explain the recently demonstrated protective effects
      of this D-amino acid against PCP-induced behavioral alterations, such as ataxic
      behavior. 

PMID- 25979767
TI  - The role of purinergic signalling in the musculoskeletal system.
AB  - Accumulating evidence now suggests that purinergic signalling exerts significant
      regulatory effects in the musculoskeletal system. In particular, it has emerged
      that extracellular nucleotides are key regulators of bone cell differentiation,
      survival and function. This review discusses our current understanding of the
      direct effects of purinergic signalling in bone, cartilage and muscle. 

PMID- 25979768
TI  - Purinergic signalling in the urinary bladder.
AB  - It is well established that in most species, exocytotic vesicular release of ATP
      from parasympathetic neurons contributes to contraction of the bladder. However,
      ATP is released not only from parasympathetic nerves, but also from the
      urothelium. During bladder filling, the urothelium is stretched and ATP is
      released from the umbrella cells thereby activating mechanotransduction pathways.
      ATP release can also be induced by various mediators present in the urine and
      and/or released from nerves or other components of the lamina propria. Urothelial
      release of ATP is mainly attributable to vesicular transport or exocytosis and,
      to a smaller extent, to pannexin hemichannel conductive efflux. After release,
      ATP acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate
      the voiding reflex and to mediate the sensation of bladder filling and urgency.
      ATP also acts on suburothelial interstitial cells/myofibroblasts generating an
      inward Ca(2+) transient that via gap junctions could provide a mechanism for long
      distance spread of signals from the urothelium to the detrusor muscle. ATP
      release can be affected by urological diseases, e.g., interstitial cystitis and
      both the mechanisms of release and the receptors activated by ATP may be targets
      for future drugs for treatment of lower urinary tract disorders. 

PMID- 25979769
TI  - Integrating genomics in head and neck cancer treatment: Promises and pitfalls.
AB  - Head and neck squamous cell carcinomas (HNSCC) represent a multifactorial disease
      of poor prognosis. They have lagged behind other cancers in terms of personalized
      therapy. With expansion and high throughput sequencing methods, recent landmark
      exonic studies and Cancer Genome Atlas data have identified genes relevant to
      carcinogenesis and cancer progression. Mutational profiles and rates vary widely
      depending on exposure to carcinogens, anatomic subsites and human papilloma virus
      (HPV) infection. Tumors may exhibit specific, tissue-specific, not exclusively
      HPV-related, gene alterations, such those observed in oral cavity cancers in Asia
      or Occident. Except for the PI3K pathway, the rate of mutations in HPV+ cancers
      is much lower than in tobacco/alcohol-related cancers. Somatic driver mutation
      analyses show that relatively few driver genes are druggable in HNSCC and that
      tumor suppressor gene alterations prevail. More mature for therapeutic
      applications is the oncogenic PI3K pathway, with preclinical human xenograft
      models suggesting that PI3KCA pathway mutations may be used as predictive
      biomarkers and clinical data showing efficacy of mTOR/Akt inhibitors. Therapeutic
      guidance, to date, relies on classical histoprognostic factors, anatomic subsite
      and HPV status, with integration of hierarchized supervised mutational profiling
      to provide additional therapeutic options in advanced HNSCC in a near future.
      Unsupervised controlled genomic analyses remain necessary to unravel potentially
      relevant genes. 

PMID- 25979770
TI  - Vitamin D-binding protein as a biomarker of active disease in acute intermittent
      porphyria.
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disorder
      caused by a deficiency of hepatic porphobilinogen deaminase (PBGD). The disease
      is characterized by life threatening acute neurovisceral attacks. The aim of this
      study was to identify metabolites secreted by the hepatocytes that reflect
      differential metabolic status in the liver and that may predict response to the
      acute attack treatment. Plasma vitamin D binding protein (VDBP) from a mouse
      model of AIP displayed an abnormal migration in 2D-electrophoresis that is
      efficiently recovered upon gene therapy leading to liver specific over-expression
      of the PBGD protein. The change in VDBP mobility results from a differential
      isoelectric point suggesting a post-translational modification that takes place
      preferably in the liver. Liquid chromatography-mass spectrometry (LC-MS) analysis
      of human samples before and after glycosidase treatment revealed glycosylated
      plasma VDBP specifically in patients with recurrent attacks of AIP. Glycosylated
      VDBP recovered normal values in three severely afflicted AIP patients submitted
      to therapeutic liver transplantation. Our findings suggest that post
      translational modification of VDBP might be considered as a promising biomarker
      to study and monitor the liver metabolic status in patients with AIP.
      SIGNIFICANCE: We describe an increased glycosylation of VDBP in porphyric livers.
      Normal glycosylation was recovered upon liver gene therapy in a mouse model of
      porphyria or after liver transplantation in severely afflicted patients with AIP.
      Moreover, quantification of glycosylated VDBP by our ELISA immunoassay or LC-MS
      protocol in patients undergoing PBGD-gene therapy (www.aipgene.org) may be used
      as a marker indicating improvement or normalization of the patient's hepatic
      metabolism. This article is part of a Special Issue entitled: HUPO 2014.

PMID- 25979771
TI  - Comparative proteomic study of Edwardsiella tarda strains with different degrees
      of virulence.
AB  - Edwardsiella tarda is an enteric opportunistic pathogen that causes a great loss
      in aquaculture. This species has been described as a phenotypical homogeneous
      group; in contrast, serological studies and molecular typing revealed a wide
      heterogeneity. In this work, a proteomic study of differential expression of a
      virulent isolate from turbot cultured in the Norwest of Spain in comparison with
      an avirulent collection strain was performed in order to recognize proteins
      involved in virulence. One hundred and three proteins that presented different
      abundance were successfully identified and classified into 11 functional
      categories according to their biological processes: amino acid, carbohydrate and
      lipid metabolism, tricarboxylic cycle, stress response and protein fate, protein
      synthesis, biogenesis of cellular components, cell rescue defence and virulence,
      cell membrane and transport, signal transduction and purine and pyrimidine
      metabolism. Twenty three protein spots detected only in turbot isolate were
      identified. It was shown that the same proteins appeared in different spots in
      the two isolates. Mass spectra obtained by MALDITOF/TOF of some of these proteins
      and DNA sequencing explained the changes as a result of different amino acid
      sequences. Several proteins related with the virulence of E. tarda (FliC, ArnA or
      FeSODI) were only detected in the turbot European isolate. This article is part
      of a Special Issue entitled: HUPO 2014. 

PMID- 25979772
TI  - Stable isotope labeling by amino acids in cell culture based proteomics reveals
      differences in protein abundances between spiral and coccoid forms of the gastric
      pathogen Helicobacter pylori.
AB  - Helicobacter pylori (H. pylori) is a epsilon-proteobacterium that colonizes the
      stomach of about half of the world's population. Persistent infections have been
      associated with several gastric diseases. Mainly rod- or spiral shaped but also
      coccoid H. pylori forms have been isolated from mucus layer biopsies of patients.
      It is still being debated whether the coccoid form can be transformed back into
      the spiral form or whether this morphology is a result of bacterial cell death or
      persistence. We established stable isotope labeling by amino acids in cell
      culture (SILAC) for quantitative proteomics of H. pylori and applied it to
      investigate differences between the spiral and the coccoid morphology. We
      detected 72% and were able to relatively quantify 47% of the H. pylori proteome.
      Proteins involved in cell division and transcriptional and translational
      processes showed a lower abundance in coccoid cells. Additionally, proteins
      related to host colonization, including CagA, the arginase RocF, and the TNF
      alpha inducing protein were down-regulated. The fact that outer membrane proteins
      were observed at higher abundances might represent a mechanism for immune evasion
      but also preserves adherence to host cells. The established protocol for relative
      protein quantification of H. pylori samples offers new possibilities for research
      on H. pylori. BIOLOGICAL SIGNIFICANCE: Our study shows that SILAC can be employed
      to study protein abundance changes in H. pylori. We have chosen to establish
      SILAC for H. pylori because it facilitates fractionation on both, protein and
      peptide level and thus enables deep proteome coverage. Furthermore, SILAC allows
      robust and highly accurate protein quantification. The manuscript includes a
      detailed description of the applied method, suggestions for further improvement
      as well as a practical application. The investigation of differences between the
      coccoid and infectious spiral morphology of H. pylori with SILAC revealed the
      regulation of proteins that are involved in host colonization, motility, cell
      division as well as transcriptional and translational processes. The data will
      help molecular biologist to focus on relevant pathways that were found to be
      regulated in response to morphological changes. Furthermore, the application of
      SILAC offers new possibilities to study the biology of H. pylori. It enables to
      monitor protein abundance changes in response to certain stimuli such as oxygen
      stress or antibiotics. Moreover, SILAC raises the possibility to study co
      cultures of host cells and H. pylori on protein level. Additionally, pulsed SILAC
      experiments enable the quantification of protein turnover.

PMID- 25979773
TI  - Is isolation of comprehensive human plasma peptidomes an achievable quest?
AB  - The low molecular weight (LMW; <10kDa)* plasma peptidome has been considered a
      source of useful diagnostic biomarkers and potentially therapeutic molecules, as
      it contains many cytokines, peptide hormones, endogenous peptide products and
      potentially bioactive fragments derived from the parent proteome. The small size
      of the peptides allows them almost unrestricted vascular and interstitial access,
      and hence distribution across blood-brain barriers, tumour and other vascular
      permeability barriers. Therefore, the peptidome may carry specific signatures or
      fingerprints of an individual's health, wellbeing or disease status. This occurs
      primarily because of the advantage the peptidome has in being readily accessible
      in human blood and/or other biofluids. However, the co-expression of highly
      abundant proteins (>10kDa) and other factors present inherently in human plasma
      make direct analysis of the blood peptidome one of the most challenging tasks
      faced in contemporary analytical biochemistry. A comprehensive compendium of
      extraction and fractionation tools has been collected concerning the isolation
      and micromanipulation of peptides. However, the search for a reliable, accurate
      and reproducible single or combinatorial separation process for capturing and
      analysing the plasma peptidome remains a challenge. This review outlines current
      techniques used for the separation and detection of plasma peptides and suggests
      potential avenues for future investigation. This article is part of a Special
      Issue entitled: HUPO 2014. 

PMID- 25979774
TI  - pFind-Alioth: A novel unrestricted database search algorithm to improve the
      interpretation of high-resolution MS/MS data.
AB  - Database search is the dominant approach in high-throughput proteomic analysis.
      However, the interpretation rate of MS/MS spectra is very low in such a
      restricted mode, which is mainly due to unexpected modifications and irregular
      digestion types. In this study, we developed a new algorithm called Alioth, to be
      integrated into the search engine of pFind, for fast and accurate unrestricted
      database search on high-resolution MS/MS data. An ion index is constructed for
      both peptide precursors and fragment ions, by which arbitrary digestions and a
      single site of any modifications and mutations can be searched efficiently. A new
      re-ranking algorithm is used to distinguish the correct peptide-spectrum matches
      from random ones. The algorithm is tested on several HCD datasets and the
      interpretation rate of MS/MS spectra using Alioth is as high as 60%-80%. Peptides
      from semi- and non-specific digestions, as well as those with unexpected
      modifications or mutations, can be effectively identified using Alioth and
      confidently validated using other search engines. The average processing speed of
      Alioth is 5-10 times faster than some other unrestricted search engines and is
      comparable to or even faster than the restricted search algorithms tested. 

PMID- 25979775
TI  - Identification of target antigens of naturally occurring autoantibodies in
      cerebrospinal fluid.
AB  - Naturally occurring autoantibodies have natural physiologic functions related to
      normal cell processes. However, the repertoire of naturally occurring
      autoantibodies against neuronal antigens in CSF is unclear. The purpose of this
      study was to identify naturally occurring autoantibodies against neuronal
      antigens in CSF from patients with various neurologic diseases by proteomics
      based analysis. The CSF samples were collected from 77 patients with various
      neurologic disorders. The antigen source for 2-dimensional immunoblotting was the
      SH-SY5Y human neuroblastoma cell line. There were 8 spots recognized in CSF from
      more than one-fourth of the 77 patients including all patient groups and these
      spots were recognized in intravenous immunoglobulin preparations. These antigen
      spots were identified as heat shock 105-kDa/110-kDa protein 1, isoform CRA_b, 78
      kDa glucose-regulated protein, heat shock cognate 71-kDa protein, tubulin beta
      chain, vimentin (2 spots), and 60-kDa heat shock protein, mitochondrial; we could
      not identify the protein name corresponding to 1 of the 8 spots. In summary,
      there were 6 proteins identified that were main target antigens that reacted with
      naturally occurring autoantibodies in CSF from patients with varied neurologic
      disorders; the functions of autoantibodies against the identified antigens are
      unknown and may be clarified with further studies. BIOLOGICAL SIGNIFICANCE:
      Naturally occurring autoantibodies may have important functions in tissue
      homeostasis. In this study, we identified 6 common target antigens that reacted
      with autoantibodies in cerebrospinal fluid (CSF) from patients, independent of
      disease type. These findings may clarify the importance of naturally occurring
      autoantibodies in CSF and the use of these antibodies potentially may be a novel
      therapy for various neurologic disorders.

PMID- 25979776
TI  - Medication Use Among Nursing Home Residents With Severe Dementia: Identifying
      Categories of Appropriateness and Elements of a Successful Intervention.
AB  - BACKGROUND: Seniors with severe dementia residing in nursing homes (NHs)
      frequently receive large numbers of medications. With disease progression, the
      medications' harm-benefit ratio changes and they need to be reviewed, adjusted,
      or discontinued. Evidence on successful interventions to optimize medication use
      among these residents is lacking. OBJECTIVES: The objective of the study was to
      identify categories of appropriateness for medications as well as successful
      interventions or elements thereof to improve medication use in NH residents with
      severe dementia, suitable for use in Canada. METHODS: A scoping literature review
      was performed to identify criteria and categories of appropriateness of
      medications for these residents as well as elements of successful interventions
      to optimize medication use. A 15-member multidisciplinary Delphi panel was
      convened to evaluate the applicability of these findings for NHs in a Canadian
      province. RESULTS: The scoping review identified 1 study presenting categories of
      appropriateness specific to residents with severe dementia and 35 interventions
      aimed at reducing drug-drug interactions, inappropriate use of specific drug
      classes, inappropriate drug use overall, or polypharmacy. Regarding
      appropriateness, the Delphi panel agreed on the categorization of 63 medications
      or medication classes as "generally," "sometimes," or "rarely appropriate." The
      main elements of interventions successful in improving appropriate medication use
      in NH residents with dementia also were approved by the Delphi panel (ie,
      medication reviews using criteria of appropriateness, educational and training
      sessions, and interdisciplinary case conferences). CONCLUSIONS: These results may
      be used to develop an intervention to optimize medication use in NH residents
      with severe dementia.

PMID- 25979777
TI  - Components of the Frailty Phenotype in Relation to the Frailty Index: Results
      From the Toulouse Frailty Platform.
AB  - OBJECTIVES: The frailty phenotype proposed by Fried and colleagues is a widely
      used frailty screening instrument, consisting of 5 components: weight loss,
      exhaustion, low grip strength, slow gait speed, and low physical activity.
      Although equally considered in the computation of the frailty phenotype score,
      each of the components may present a specific and different weight in clinical
      practice. The objective of this study was to estimate the weight of each frailty
      phenotype component in terms of age-related deficit accumulation, defined
      according to the frailty index (FI) proposed by Rockwood and colleagues. DESIGN:
      Cross-sectional study. PARTICIPANTS: Data were used from 484 frail older adults
      admitted to a geriatric day hospital unit of the Toulouse University Hospital.
      MEASUREMENTS: The outcome measure was a 35-item FI based on data routinely
      collected as part of a clinical assessment. Descriptive statistics and linear
      regression analyses were used to determine which components of the frailty
      phenotype were most strongly associated with the FI. RESULTS: The mean age of the
      participants was 83.2 (SD 6.0). All components of the frailty phenotype were
      significantly associated with the FI, but the magnitude of the associations
      varied. Linear regression analyses, adjusted for age, sex, and educational level
      showed that slow gait speed was the most informative component (B = 0.129, P <
      .001) and weight loss was the least informative component (B = 0.027, P = .037).
      The combination of slow gait speed and low physical activity was the most
      strongly associated with the FI (B = 0.144, P < .001). CONCLUSION: Of the 5
      components of the phenotype, slow gait speed seems to be the key indicator of
      frailty.

PMID- 25979778
TI  - Day Care Centers for Seniors in Singapore: Looking Back and Looking Ahead.
AB  - The burden of care for frail elderly persons on families and the society is ever
      real as our population ages. Given the dual-income nature of many working
      families, day care centers offer a strong alternative to nursing homes for
      families wishing to provide custodial care and meaningful engagement for seniors
      while continuing to uphold their filial duties. Recognizing this, several
      initiatives, such as SPICE (Singapore Programme for Integrated Care for the
      Elderly) and Weekend Respite Care, have been launched to enhance the services of
      Singapore's day care centers. This article traces the evolution of this process,
      distills current challenges, and offers policy recommendations to improve
      Singapore's day care services for seniors.

PMID- 25979779
TI  - Introduction.

PMID- 25979780
TI  - Current status of newborn screening worldwide: 2015.
AB  - Newborn screening describes various tests that can occur during the first few
      hours or days of a newborn's life and have the potential for preventing severe
      health problems, including death. Newborn screening has evolved from a simple
      blood or urine screening test to a more comprehensive and complex screening
      system capable of detecting over 50 different conditions. While a number of
      papers have described various newborn screening activities around the world,
      including a series of papers in 2007, a comprehensive review of ongoing
      activities since that time has not been published. In this report, we divide the
      world into 5 regions (North America, Europe, Middle East and North Africa, Latin
      America, and Asia Pacific), assessing the current NBS situation in each region
      and reviewing activities that have taken place in recent years. We have also
      provided an extensive reference listing and summary of NBS and health data in
      tabular form.

PMID- 25979781
TI  - Newborn screening for spinal muscular atrophy: Anticipating an imminent need.
AB  - Spinal muscular atrophy (SMA) is the most common genetic cause of infant
      mortality. Children with type I SMA typically die by the age of 2 years. Recent
      progress in gene modification and other innovative therapies suggest that
      improved outcomes may soon be forthcoming. In animal models, therapeutic
      intervention initiated before the loss of motor neurons alters SMA phenotype and
      increases lifespan. Presently, supportive care including respiratory,
      nutritional, physiatry, and orthopedic management can ameliorate clinical
      symptoms and improve survival rates if SMA is diagnosed early in life. Newborn
      screening could help optimize these potential benefits. A recent report
      demonstrated that SMA detection can be multiplexed at minimal additional cost
      with the assay for severe combined immunodeficiency, already implemented by many
      newborn screening programs. The public health community should remain alert to
      the rapidly changing developments in early detection and treatment of SMA. 

PMID- 25979782
TI  - Detection of critical congenital heart defects: Review of contributions from
      prenatal and newborn screening.
AB  - In 2011, statewide newborn screening programs for critical congenital heart
      defects began in the United States, and subsequently screening has been
      implemented widely. In this review, we focus on data reports and collection
      efforts related to both prenatal diagnosis and newborn screening. Defect
      specific, maternal, and geographic factors are associated with variations in
      prenatal detection, so newborn screening provides a population-wide safety net
      for early diagnosis. A new web-based repository is collecting information on
      newborn screening program policies, quality indicators related to screening
      programs, and specific case-level data on infants with these defects. Birth
      defects surveillance programs also collect data about critical congenital heart
      defects, particularly related to diagnostic timing, mortality, and services.
      Individuals from state programs, federal agencies, and national organizations
      will be interested in these data to further refine algorithms for screening in
      normal newborn nurseries, neonatal intensive care settings, and other special
      populations; and ultimately to evaluate the impact of screening on outcomes. 

PMID- 25979783
TI  - Newborn screening for sickle cell diseases in the United States: A review of data
      spanning 2 decades.
AB  - Sickle cell disease is a group of disorders, the majority of which are detected
      through state newborn screening programs. There is limited knowledge of disease
      prevalence in the U.S. POPULATION: We report 20 years of case finding and
      laboratory data for sickle cell disease and trait to assist in: planning for
      health services delivery; providing data for researchers; aiding in tracking
      health outcome trends; and assessing sickle gene prevalence in the newborn
      population. During the 20-year period, there were 39,422 confirmed cases of
      sickle cell disease among 76,527,627 newborn births screened (1:1941) and
      1,107,875 laboratory reports of probable sickle trait among 73,951,175 newborn
      births screened (1:67). The highest sickle cell disease incidence during the 20
      years was in the District of Columbia (1:437) followed by Mississippi (1:683) and
      South Carolina (1:771). For sickle cell trait, the highest incidences were in the
      District of Columbia (1:22), Mississippi (1:26), and South Carolina (1:31).

PMID- 25979784
TI  - Co-digestion of municipal sludge and external organic wastes for enhanced biogas
      production under realistic plant constraints.
AB  - A bench-scale investigation was conducted to select external organic wastes and
      mixing ratios for co-digestion with municipal sludge at the F. Wayne Hill Water
      Resources Center (FWHWRC), Gwinnett County, GA, USA to support a combined heat
      and power (CHP) project. External wastes were chosen and used subject to two
      constraints: a) digester retention time no lower than 15 d; and b) total biogas
      (methane) production not to exceed a specific target level based on air permit
      constraints on CO2 emissions. Primary sludge (PS), thickened waste activated
      sludge (TWAS) and digested sludge collected at the FWHWRC, industrial liquid
      waste obtained from a chewing gum manufacturing plant (GW) and dewatered fat-oil
      grease (FOG) were used. All sludge and waste samples were characterized and their
      ultimate digestibility was assessed at 35  degrees C. The ultimate COD to methane
      conversion of PS, TWAS, municipal sludge (PS + TWAS; 40:60 w/w TS basis), GW and
      FOG was 49.2, 35.2, 40.3, 72.7, and 81.1%, respectively. Co-digestion of
      municipal sludge with GW, FOG or both, was evaluated using four bench-scale,
      mesophilic (35  degrees C) digesters. Biogas production increased significantly
      and additional degradation of the municipal sludge between 1.1 and 30.7% was
      observed. Biogas and methane production was very close to the target levels
      necessary to close the energy deficit at the FWHWRC. Co-digestion resulted in an
      effluent quality similar to that of the control digester fed only with the
      municipal sludge, indicating that co-digestion had no adverse effects. Study
      results prove that high methane production is achievable with the addition of
      concentrated external organic wastes to municipal digesters, at acceptable higher
      digester organic loadings and lower retention times, allowing the effective
      implementation of CHP programs at municipal wastewater treatment plants, with
      significant cost savings.

PMID- 25979785
TI  - Fractionation and release behaviors of metals (In, Mo, Sr) from industrial
      sludge.
AB  - Little is known on the fate of rare metals in the environment and the associated
      risks. The fractionation and release of three metals of an industrial sludge were
      assessed. The average concentration ranges from 39.3 to 41.5 mg/kg for indium
      (In), 43.1-77.8 mg/kg for molybdenum (Mo), and 131.1-376.4 mg/kg for strontium
      (Sr). Sequential extraction results implied that In was mobile, while Mo and Sr
      were immobile. However, experimental results from effects of Eh/pH revealed that
      In was slightly mobile under acidic (pH 4.5) in Eh range of 210-260 mV, and
      immobile under alkaline conditions (9.0) in Eh range of -250 to 125 mV. The
      release of Mo was slightly mobile under acidic conditions. However, Mo was very
      mobile under alkaline conditions and it increased with decreasing Eh. The release
      of Sr was significant under acidic conditions; however, it was immobile under
      alkaline conditions. Solubility and adsorption as affected by pH, and speciation
      could explain their release behaviors. Discrepancy in predictions from sequential
      extraction and actual observation from Eh/pH experiments was discussed.

PMID- 25979786
TI  - Supportive text messages to reduce mood symptoms and problem drinking in patients
      with primary depression or alcohol use disorder: protocol for an implementation
      research study.
AB  - BACKGROUND: Depression and Alcohol Use Disorders (AUDs) are two leading causes of
      disability worldwide and are associated with significant treatment challenges
      requiring new, innovative, cost-effective and technologically-based therapies
      including the use of supportive text messages. OBJECTIVE: To determine the
      feasibility and effectiveness of supportive text messages in long-term follow-up
      to reduce mood symptoms and problem drinking in patients with Depression or AUD
      respectively and to explore the usefulness of self-reports of health services
      utilization as an outcomes measure. METHODS: This will be a longitudinal,
      prospective, parallel-design, two-arm, placebo-controlled single-rater-blinded
      randomized clinical trial with a recruitment period of 6 months and an
      observation period of 12 months for each participant, with two strata based on
      primary diagnosis of Major Depressive Disorder or AUD. The sample size will be
      120, with about 60 patients randomized from each primary diagnostic grouping.
      Patients in all intervention groups will receive twice-daily supportive SMS text
      messages for 3 months and then daily supportive text messages for the next three
      months. Patients will also receive a phone call every two weeks from the research
      assistant assigning treatment allocation to confirm that they are still receiving
      the text messages and to thank them for taking part in the study. Patients in the
      control group will receive no text messages but will also receive a phone call
      from the same research assistant every two weeks to thank them for taking part in
      the study. RESULTS: The study starts in April 2015 and ends in September 2016. It
      is envisaged that both qualitative and quantitative primary and secondary
      outcomes, including patient perceptions of the intervention, will shed light on
      the feasibility of using automated supportive text message interventions in long
      term for patients with Depression and AUD. This will inform a full-scale clinical
      trial. CONCLUSIONS: The paradigm for behavior change using text messages as a
      patient-direct intervention is consistent with a cognitive behavior therapy
      approach and addictions counselling principles. Given the automaticity of the
      messages, we anticipate that if the intervention proves successful, it will
      represent a low cost strategy that will be readily available and can bring relief
      to patients in hard-to-reach areas with limited access to psychological
      therapies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02327858;
      https://clinicaltrials.gov/ct2/show/NCT02327858 (Archived by WebCite at
      https://clinicaltrials.gov/ct2/show/NCT02327858).

PMID- 25979788
TI  - Widespread cortical alpha-ERD accompanying visual oddball target stimuli is
      frequency but non-modality specific.
AB  - Previous studies have shown that alpha event-related desynchronization (alpha
      ERD) is associated with reaction to visual stimuli in oddball paradigm, as a
      reflection of attention allocation and memory updating. The present study tested
      the hypothesis that it reflects a modality and/or frequency specific mechanism.
      Electroencephalography (EEG) recordings (64 channels) were performed on 18
      healthy subjects during visual, auditory, somatosensory, and pain oddball
      paradigms. Low- and high-frequency alpha-rhythm were analyzed on individual
      basis, and their sources were estimated by low resolution brain electromagnetic
      tomography (LORETA). alpha-ERD, served as an index of cortical activation, was
      computed on the cortical voxel level and compared across the conditions (target
      vs. non-target), alpha sub-bands (lower vs. higher frequency), and modalities
      (visual, auditory, somatosensory, and pain). The results showed that visual alpha
      ERD was mainly generated from occipital cortex for both target and non-target
      conditions. Its magnitude was enhanced across widespread cortical regions (e.g.,
      bilateral occipital, parietal, and frontal areas) in the target condition and was
      greater in high-frequency alpha-band. Finally, alpha-ERD difference between
      target and non-target conditions was not higher in visual than that in other
      control modalities. All these findings indicated that human high-frequency alpha
      ERD reflects cognitive attention processes underlying reaction to oddball target
      stimuli regardless of stimulus modality. 

PMID- 25979787
TI  - Endocannabinoid-mediated improvement on a test of aversive memory in a mouse
      model of fragile X syndrome.
AB  - Silencing the gene FMR1 in fragile X syndrome (FXS) with consequent loss of its
      protein product, FMRP, results in intellectual disability, hyperactivity,
      anxiety, seizure disorders, and autism-like behavior. In a mouse model (Fmr1
      knockout (KO)) of FXS, a deficit in performance on the passive avoidance test of
      learning and memory is a robust phenotype. We report that drugs acting on the
      endocannabinoid (eCB) system can improve performance on this test. We present
      three lines of evidence: (1) Propofol (reported to inhibit fatty acid amide
      hydrolase (FAAH) activity) administered 30 min after training on the passive
      avoidance test improved performance in Fmr1 KO mice but had no effect on wild
      type (WT). FAAH catalyzes the metabolism of the eCB, anandamide, so its
      inhibition should result in increased anandamide levels. (2) The effect of
      propofol was blocked by prior administration of the cannabinoid receptor 1
      antagonist AM-251. (3) Treatment with the FAAH inhibitor, URB-597, administered
      30 min after training on the passive avoidance test also improved performance in
      Fmr1 KO mice but had no effect on WT. Our results indicate that the eCB system is
      involved in FXS and suggest that the eCB system is a promising target for
      treatment of FXS.

PMID- 25979789
TI  - The evidence does not speak for itself: The role of research evidence in shaping
      policy change for the implementation of publicly funded syringe exchange programs
      in three US cities.
AB  - BACKGROUND: A breadth of literature exists that explores the utilization of
      research evidence in policy change processes. From this work, a number of studies
      suggest research evidence is applied to change processes by policy change
      stakeholders primarily through instrumental, conceptual, and/or symbolic
      applications, or is not used at all. Despite the expansiveness of research on
      policy change processes, a deficit exists in understanding the role of research
      evidence during change processes related to the implementation of structural
      interventions for HIV prevention among injection drug users (IDU). This study
      examined the role of research evidence in policy change processes for the
      implementation of publicly funded syringe exchange services in three US cities:
      Baltimore, MD, Philadelphia, PA, and Washington, DC. METHODS: In-depth
      qualitative interviews were conducted with key stakeholders (n=29) from each of
      the study cities. Stakeholders were asked about the historical, social,
      political, and scientific contexts in their city during the policy change
      process. Interviews were transcribed and analyzed for common themes pertaining to
      applications of research evidence. RESULTS: In Baltimore and Philadelphia, the
      typological approaches (instrumental and symbolic/conceptual, respectively) to
      the applications of research evidence used by harm reduction proponents
      contributed to the momentum for securing policy change for the implementation of
      syringe exchange services. Applications of research evidence were less successful
      in DC because policymakers had differing ideas about the implications of syringe
      exchange program implementation and because opponents of policy change used
      evidence incorrectly or not at all in policy change discussions. CONCLUSION:
      Typological applications of research evidence are useful for understanding policy
      change processes, but their efficacy falls short when sociopolitical factors
      complicate legislative processes. Advocates for harm reduction may benefit from
      understanding how to effectively integrate research evidence into policy change
      processes in ways that confront the myriad of factors that influence policy
      change.

PMID- 25979790
TI  - Vocal Hyperfunction in Parents of Children With Attention Deficit Hyperactivity
      Disorder.
AB  - OBJECTIVE: The objective of this study was to evaluate the presence of habits and
      symptoms of vocal hyperfunction in the parents of children with attention deficit
      hyperactivity disorder (ADHD). METHODS: Parents of 24 children with ADHD and 30
      children of a control group completed a specific questionnaire to detect the
      hyperfunctional use of the voice (excessive talking, excessive loudness, talking
      too fast, and shouting), hoarseness, vocal fatigue, mental and physical fatigue,
      and the degree of parental concern for the vocal health of their child. RESULTS:
      Parents of children with ADHD spoke more often, faster, and stronger than the
      parents of the control group; in addition, they also used a louder volume than
      they usually used when they spoke to their children. The parents manifested more
      vocal, mental, and physical fatigue than the parents of the control group. There
      was a significant correlation between the "concern" for the vocal health of their
      children with respect to vocal symptoms of the children, the habits of vocal
      hyperfunctioning, and the symptoms suffered by the parents. CONCLUSIONS: These
      results suggest that the parents of children with ADHD change their vocal
      attitude when communicating with their children. Most likely, the increased
      concern of parents with ADHD children and their respective level of stress lead
      to hyperfunctional vocal usage. This subsequently leads to symptoms of vocal,
      physical, and mental fatigue at the end of the day.

PMID- 25979791
TI  - Screening for Voice Disorders in Older Adults (Rastreamento de Alteracoes Vocais
      em Idosos-RAVI)-Part II: Validity Evidence and Reliability.
AB  - PURPOSE: To determine the validity evidence based on the internal structure and
      relations to other variables and the reliability of an epidemiologic
      questionnaire for screening older adults with voice disorders. STUDY DESIGN: This
      is a prospective, nonrandomized, cross-sectional, validation study. METHODS: To
      assess the validity evidence based on the internal structure, 160 older adults of
      both sexes, either community-dwelling or institutionalized, completed the
      "Rastreamento de Alteracoes Vocais em Idosos" (RAVI; "Screening for Voice
      Disorders in Older Adults"). The data were analyzed using item-total and
      interitem correlations, principal component analysis, confirmatory factor
      analysis, and differential item functioning. For validity evidence based on
      relations to other variables, measures of concurrent and discriminant validity
      were calculated according to the self-reported number of factors associated with
      voice disorders. Reliability was assessed using a test-retest procedure conducted
      with 121 older adults with the same characteristics as the previous sample. In
      this stage, the reproducibility, internal consistency, and measurement error of
      the instrument were analyzed. RESULTS: The RAVI showed adequate validity evidence
      based on the internal structure and relations to other variables, as well as good
      reliability. This indicates that the results produced by the instrument are valid
      and reliable. CONCLUSIONS: The RAVI is a self-reported outcome questionnaire that
      yields valid and reliable responses for epidemiologic detection of voice
      disorders in older adults and can be easily administered by any health care
      provider. Further ongoing studies will assess accuracy measures and cutoff values
      of the RAVI.

PMID- 25979792
TI  - Screening for Voice Disorders in Older Adults (Rastreamento de Alteracoes Vocais
      em Idosos--RAVI)--Part I: Validity Evidence Based on Test Content and Response
      Processes.
AB  - PURPOSE: To identify the validity evidence based on the content and response
      processes of the Rastreamento de Alteracoes Vocais em Idosos (RAVI; "Screening
      for Voice Disorders in Older Adults"), an epidemiologic screening for voice
      disorders in older adults. STUDY DESIGN: This is a prospective, nonrandomized,
      cross-sectional, validation study. METHODS: Criteria for defining the domains and
      elaborating the questions were established to confirm the validity evidence based
      on the content. A multidisciplinary committee of 19 experts evaluated the
      questions, and the relevance and representation of the domains were analyzed
      using the Content Validity Index for Items (CVI-I) and the Content Validity Index
      (CVI), respectively. For validity evidence based on the response processes, 40
      individuals of both sexes, aged >=60 years, were stratified by demographic and
      socioeconomic condition. They responded to the RAVI, made suggestions, and their
      verbal and nonverbal reactions were observed. RESULTS: The first version of the
      RAVI consisted of 20 questions related to sensations and perceptions associated
      with the voice. Although the CVI value of 0.80 was satisfactory, the CVI-I and
      the suggestions of the expert committee indicated that the scale needed to be
      reformulated. Consultation with older adults indicated a need for further
      adjustment. The preliminary version of the RAVI consisted of 16 questions.
      CONCLUSIONS: The two aspects of validity evidence described in the present study
      were essential for adapting the questions to better fit the construct of the
      questionnaire. Other aspects of validity evidence and reliability analysis will
      be described in part II of this study.

PMID- 25979793
TI  - Validity of predictive models of stress relaxation in selected dental polymers.
AB  - OBJECTIVE: The goal of this investigation was to assess validity of predictive
      models of stress relaxation in dental polymers when applied to extended master
      curves generated from short time experimental data by WLF time temperature
      superposition method. METHODS: The stress relaxation modulus changes with time at
      three different temperatures near the ambient body temperature were determined
      for selected mono-methacrylate (PEMA and PMMA) and dimethacrylate (bis-acryl)
      dental polymers. WLF time-temperature superposition procedure of logarithmic
      shift of the data from other temperatures to those at 37 degrees C was used to
      generate extended master curves of relaxation modulus changes with time. The
      extended data were analyzed for conformity to three different predictive models
      of stress relaxation including Maxwell, KWW stretched exponential function and
      Nutting's power law equation. RESULTS: Maxwell model was found to be a poor fit
      for the extended data in all polymers tested, but the data showed a much better
      fit for KWW (0.870<R(2)<0.901) and Nutting's (0.980<R(2)<0.986) models. The non
      exponential factor beta in the KWW function and the fractional power exponent n
      in Nutting's equation were both significantly different for PEMA based system
      when compared to that of PMMA and bis-acryl systems. SIGNIFICANCE: The mean
      values of beta in KWW function and power exponent n in Nutting's equation for
      PEMA resin is consistent with significant viscoplastic contribution to its
      deformation under stress unlike in PMMA and bis-acryl resin systems. This may
      have significant bearing for PEMA use in medium to longer term stress-bearing
      applications even as a temporization material.

PMID- 25979794
TI  - Elution of monomer from different bulk fill dental composite resins.
AB  - OBJECTIVE: The purpose of this study was to evaluate the elution of Bis-GMA,
      TEGDMA, HEMA, and Bis-EMA monomers from six bulk fill composite resins over four
      different time periods, using HPLC. METHODS: Six different composite resin
      materials were used in the present study: Tetric Evo Ceram Bulk Fill (Ivoclar
      Vivadent, Amherst, NY), X-tra Fill (VOCO, Cuxhaven, Germany), Sonic Fill (Kerr,
      Orange, CA, USA), Filtek Bulk Fill (3M ESPE Dental Product, St. Paul, MN), SDR
      (Dentsply, Konstanz, Germany), EQUIA (GC America INC, Alsip, IL). The samples
      (4mm thickness, 5mm diameter) were prepared and polymerized for 20s with a light
      emitted diode unit. After fabrication, each sample was immediately immersed in
      75wt% ethanol/water solution used as extraction fluid and stored in the amber
      colored bottles at room temperature. Ethanol/water samples were taken (0.5mL) at
      predefined time intervals:10m (T1), 1h (T2), 24h (T3) and 30 days (T4). These
      samples were analyzed by HPLC. The obtained data were analyzed with one-way ANOVA
      and Tukey HSD at significance level of p<0.05. RESULTS: Amount of eluted Bis-EMA
      and Bis-GMA from Tetric Evo Ceram Bulk Fill and amount of eluted TEGDMA and HEMA
      from X-tra Fill higher than others composites (p<0.05). SIGNIFICANCE: Residual
      monomers were eluted from bulk fill composite resins in all time periods and the
      amount of eluted monomers was increased with time.

PMID- 25979795
TI  - Automated Quantification of Tumor Viability in a Rabbit Liver Tumor Model after
      Chemoembolization Using Infrared Imaging.
AB  - The rabbit VX2 tumor is a fast-growing carcinoma model commonly used to study new
      therapeutic devices, such as catheter-based therapies for patients with
      inoperable hepatocellular carcinoma. The evaluation of tumor viability after such
      locoregional therapies is essential to directing hepatocellular carcinoma
      management. We used infrared microspectroscopy for the automatic characterization
      and quantification of the VX2 liver tumor viability after drug-eluting beads
      transarterial chemoembolization (DEB-TACE). The protocol consisted of K-means
      clustering followed by principal component analysis (PCA) and linear discriminant
      analysis (LDA). The K-means clustering was used to classify the spectra from the
      infrared images of control or treated tumors and to build a database of many
      tissue spectra. On the basis of this reference library, the PCA-LDA analysis was
      used to build a predictive model to identify and quantify automatically tumor
      viability on unknown tissue sections. For the DEB group, the LDA model determined
      that the surface of tumor necrosis represented 91.6% +/- 8.9% (control group:
      33.1% +/- 19.6%; Mann-Whitney P = 0.0004) and the viable tumor 2.6% +/- 4%
      (control group: 62.2% +/- 15.2%; Mann-Whitney P = 0.0004). Tissue quantification
      measurements correlated well with tumor necrosis (r = 0.827, P < 0.0001) and
      viable tumor (r = 0.840, P < 0.0001). Infrared imaging and PCA-LDA analysis could
      be helpful for easily assessing tumor viability.

PMID- 25979797
TI  - Rigorous, robust and systematic: Qualitative research and its contribution to
      burn care. An integrative review.
AB  - Qualitative methods are progressively being implemented by researchers for
      exploration within healthcare. However, there has been a longstanding and wide
      ranging debate concerning the relative merits of qualitative research within the
      health care literature. This integrative review aimed to exam the contribution of
      qualitative research in burns care and subsequent rehabilitation. Studies were
      identified using an electronic search strategy using the databases PubMed,
      Cumulative Index of Nursing and Allied Health Literature (CINAHL), Excerpta
      Medica database (EMBASE) and Scopus of peer reviewed primary research in English
      between 2009 to April 2014 using Whittemore and Knafl's integrative review method
      as a guide for analysis. From the 298 papers identified, 26 research papers met
      the inclusion criteria. Across all studies there was an average of 22
      participants involved in each study with a range of 6-53 participants conducted
      across 12 nations that focussed on burns prevention, paediatric burns,
      appropriate acquisition and delivery of burns care, pain and psychosocial
      implications of burns trauma. Careful and rigorous application of qualitative
      methodologies promotes and enriches the development of burns knowledge. In
      particular, the key elements in qualitative methodological process and its
      publication are critical in disseminating credible and methodologically sound
      qualitative research. 

PMID- 25979798
TI  - Full thickness facial burns: Outcomes following orofacial rehabilitation.
AB  - PURPOSE: To document orofacial rehabilitation and outcomes after full thickness
      orofacial burn. METHODS: Participants included 12 consecutive patients presenting
      with full thickness orofacial burns. A group of 120 age-matched healthy
      participants was recruited for normative comparison. Non-surgical exercise was
      initiated within 48 h of admission and continued until wounds had healed,
      circumoral scar tissue had stabilised and functional goals were achieved to the
      best of the patient's ability. Outcomes were documented using vertical and
      horizontal mouth opening measures at start and end of treatment and therapy
      duration was recorded. RESULTS: At commencement of treatment, participants had
      significantly (p<0.001) reduced vertical and horizontal mouth opening range
      compared to controls. Average duration of orofacial contracture management was
      550 days, with half requiring >2 years rehabilitation. By end of treatment,
      significant (p<0.01) positive improvement in vertical and horizontal mouth
      opening had been achieved, however measures had returned to lower limits of
      normal function and remained significantly (p<0.05) reduced compared to the
      control group. CONCLUSION: This study demonstrates that although positive gains
      can be achieved through non-surgical exercise after full thickness burn, the
      duration of rehabilitation is considerable and some degree of long term loss in
      functional mouth opening remains.

PMID- 25979799
TI  - Evaluation of a novel scoring and grading model for VP-based exams in
      postgraduate nurse education.
AB  - For Virtual Patient-based exams, several scoring and grading methods have been
      proposed, but none have yet been validated. The aim of this study was to evaluate
      a new scoring and grading model for VP-based exams in postgraduate paediatric
      nurse education. The same student group of 19 students performed a VP-based exam
      in three consecutive courses. When using the scoring and grading assessment
      model, which contains a deduction system for unnecessary or unwanted actions, a
      progression was found in the three courses: 53% of the students passed the first
      exam, 63% the second and 84% passed the final exam. The most common reason for
      deduction of points was due to students asking too many interview questions or
      ordering too many laboratory tests. The results showed that the new scoring model
      made it possible to judge the students' clinical reasoning process as well as
      their progress. 

PMID- 25979796
TI  - Persisting effects of a PBDE metabolite, 6-OH-BDE-47, on larval and juvenile
      zebrafish swimming behavior.
AB  - Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants that are
      widely detected in the environment, biota, and humans. In mammals, PBDEs can be
      oxidatively metabolized to form hydroxylated polybrominated diphenyl ethers (OH
      BDEs). While studies have examined behavioral deficits or alterations induced by
      exposure to PBDEs in both rodents and fish, no study to date has explored
      behavioral effects from exposure to OH-BDEs, which have been shown to have
      greater endocrine disrupting potential compared to PBDEs. In the present study,
      zebrafish (Danio rerio) were exposed during embryonic and larval development (0-6
      days post fertilization, dpf) to a PBDE metabolite, 6-hydroxy, 2,2',4,4'
      tetrabromodiphenyl ether (10-50 nM) and then examined for short and long-term
      behavioral effects. Exposed zebrafish tested as larvae (6 dpf) showed an altered
      swimming response to light-dark transitions, exhibiting hypoactivity in light
      periods compared to control fish. When fish exposed from 0-6 dpf were tested as
      juveniles (45 dpf), they showed an increased fear response and hyperactivity in
      response to tests of novel environment exploration and habituation learning.
      These results demonstrate that early life exposure to a PBDE metabolite can have
      immediate or later life (more than a month after exposure) effects on activity
      levels, habituation, and fear/anxiety.

PMID- 25979800
TI  - Evaluation of a filmed clinical scenario as a teaching resource for an
      introductory pharmacology unit for undergraduate health students: A pilot study.
AB  - BACKGROUND: Simulation is frequently being used as a learning and teaching
      resource for both undergraduate and postgraduate students, however reporting of
      the effectiveness of simulation particularly within the pharmacology context is
      scant. OBJECTIVES: The aim of this pilot study was to evaluate a filmed simulated
      pharmacological clinical scenario as a teaching resource in an undergraduate
      pharmacological unit. DESIGN: Pilot cross-sectional quantitative survey. SETTING:
      An Australian university. PARTICIPANTS: 32 undergraduate students completing a
      healthcare degree including nursing, midwifery, clinical science, health science,
      naturopathy, and osteopathy. METHODS: As a part of an undergraduate online
      pharmacology unit, students were required to watch a filmed simulated
      pharmacological clinical scenario. To evaluate student learning, a measurement
      instrument developed from Bloom's cognitive domains (knowledge, comprehension,
      application, analysis, synthesis and evaluation) was employed to assess
      pharmacological knowledge conceptualisation and knowledge application within the
      following fields: medication errors; medication adverse effects; medication
      interactions; and, general pharmacology. RESULTS: The majority of participants
      were enrolled in an undergraduate nursing or midwifery programme (72%). Results
      demonstrated that the majority of nursing and midwifery students (56.52%) found
      the teaching resource complementary or more useful compared to a lecture although
      less so compared to a tutorial. Students' self-assessment of learning according
      to Bloom's cognitive domains indicated that the filmed scenario was a valuable
      learning tool. Analysis of variance indicated that health science students
      reported higher levels of learning compared to midwifery and nursing. CONCLUSION:
      Students' self-report of the learning benefits of a filmed simulated clinical
      scenario as a teaching resource suggest enhanced critical thinking skills and
      knowledge conceptualisation regarding pharmacology, in addition to being useful
      and complementary to other teaching and learning methods.

PMID- 25979801
TI  - Student nurses' recognition of early signs of abnormal vital sign recordings.
AB  - BACKGROUND: There is increasing urgency for nurses to recognize early signs of
      deterioration in patients and to take appropriate action to prevent serious
      adverse effects. OBJECTIVES: To assess respondents' ability to identify abnormal
      recordings for respiratory and heart rate, oxygen saturation level, systolic
      blood pressure, level of consciousness, urinary output and normal temperature.
      DESIGN: A descriptive observational survey. SETTING: A nursing college in Cape
      Town, South Africa. PARTICIPANTS: A sample of 77/212 (36.3%) fourth year
      students. METHODS: A self-administered adapted questionnaire was employed to
      collect demographic data and respondents' selections of recorded physiological
      values for the purpose of deciding when to call for more skilled help. RESULTS:
      The median age for 62/77 (80.5%) of the respondents was 25years; 3/76 (3.9%) had
      a previous certificate in nursing. Most respondents were female (66/76, 85.7%).
      Afrikaans was the first language preference of 33 (42.9%) respondents, followed
      by isiXhosa (31/77, 40.3%) and English (10/77, 13.0%). Most respondents (48/77,
      62.3%) recognized a normal temperature reading (35-38.4 degrees C). However,
      overall there would have been delays in calling for more skilled assistance in
      288/416 (69.2%) instances of critical illness for a high-score MEWS of 3 and in
      226/639 (35.4%) instances at a medium-score MEWS of 2 for physiological
      parameters. In 96/562 (17.1%) instances, respondents would have called for
      assistance for a low-score MEWS of 1. CONCLUSIONS: Non-recognition of
      deterioration in patients' clinical status and delayed intervention by nurses has
      implications for the development of serious adverse events. The MEWS is
      recommended as a track-and-trigger system for nursing curricula in South Africa
      and for implementation in practice.

PMID- 25979802
TI  - Current state of evidence-based practice education for undergraduate nursing
      students in Taiwan: A questionnaire study.
AB  - BACKGROUND: Evidence-based practice (EBP) has been emphasized as the core
      competency of undergraduate nursing students and must be cultivated before
      graduation. However, there is limited information of EBP education for
      undergraduate nursing students in Taiwan. OBJECTIVES: The purpose of this study
      was to investigate the current state of EBP education for undergraduate nursing
      students in Taiwan. DESIGN: A self-developed questionnaire, validated by
      experienced educators, was designed to explore curriculum design, teaching
      resources, qualification of teachers, and barriers regarding EBP education.
      PARTICIPANTS: A total of 21 nursing schools and colleges participated. The chair
      of each recommended a faculty member involved in teaching EBP as the school's
      representative to fill out the questionnaire. RESULTS: Among the 21 nursing
      schools and colleges, 18 (85.7%) had implemented EBP education in the curriculum.
      Among these schools, 22.2% conducted an independent EBP course, 50% incorporated
      EBP concepts into other courses, and the remainder offered both kinds of EBP
      courses. Multiple strategies were incorporated to teach the EBP. Less than 35% of
      the schools had designed or adopted standardized teaching materials and evaluated
      students' learning outcomes. Although 55.6% of the schools reimbursed faculty for
      participation in EBP training, 39% of their faculty members who taught EBP did
      not receive any EBP training. Shortage of qualified faculty and limited
      opportunity to involve students in evidence-based applications were reported as
      major obstacles to teaching EBP. CONCLUSIONS: EBP education has already gained
      the attention of nursing schools in Taiwan. However, lack of comprehensive EBP
      training among teachers and the difficulty of teaching clinical application of
      EBP require special consideration. In order to promote EBP education in
      undergraduate nursing curriculums, we suggest that nursing schools reinforce and
      support faculty to participate in formal EBP training. Also needed is a
      systematic curriculum design with multiple teaching strategies and links with
      clinical practicum.

PMID- 25979803
TI  - Implantable vaccine development using in vitro antigen-pulsed macrophages
      absorbed on laser micro-structured Si scaffolds.
AB  - To overcome the limiting antigenic repertoire of protein sub-units and the side
      effects of adjuvants applied in second generation vaccines, the present work
      combined in vitro and in vivo manipulations to develop biomaterials allowing
      natural antigen-loading and presentation in vitro and further activation of the
      immune response in vivo. 3-dimensional laser micro-textured implantable Si
      scaffolds supported mouse macrophage adherence, allowed natural seeding with
      human serum albumin (antigen) and specific antibody and inflammatory cytokine
      production in vitro. Implantation of Si-scaffolds loaded with antigen-activated
      macrophages induced an inflammatory reaction along with antigen-specific antibody
      production in vivo, which could be detected even 30 days post implantation.
      Analysis of implant histology using scanning electron microscopy showed that Si
      scaffolds could be stable for a 6-month period. Such technology leads to
      personalized implantable vaccines, opening novel areas of research and treatment.

PMID- 25979804
TI  - Influenza vaccination coverage of Vaccine for Children (VFC)-entitled versus
      privately insured children, United States, 2011-2013.
AB  - BACKGROUND: The Vaccines for Children (VFC) program provides vaccines at no cost
      to children who are Medicaid-eligible, uninsured, American Indian or Alaska
      Native (AI/AN), or underinsured and vaccinated at Federally Qualified Health
      Centers or Rural Health Clinics. The objective of this study was to compare
      influenza vaccination coverage of VFC-entitled to privately insured children in
      the United States, nationally, by state, and by selected socio-demographic
      variables. METHODS: Data from the National Immunization Survey-Flu (NIS-Flu)
      surveys were analyzed for the 2011-2012 and 2012-2013 influenza seasons for
      households with children 6 months-17 years. VFC-entitlement and private insurance
      status were defined based upon questions asked of the parent during the telephone
      interview. Influenza vaccination coverage estimates of children VFC-entitled
      versus privately insured were compared by t-tests, both nationally and within
      state, and within selected socio-demographic variables. RESULTS: For both seasons
      studied, influenza coverage for VFC-entitled children did not significantly
      differ from coverage for privately insured children (2011-2012: 52.0%+/-1.9%
      versus 50.7%+/-1.2%; 2012-2013: 56.0%+/-1.6% versus 57.2%+/-1.2%). Among VFC
      entitled children, uninsured children had lower coverage (2011-2012: 38.9%+/
      4.7%; 2012-2013: 44.8%+/-3.5%) than Medicaid-eligible (2011-2012: 55.2%+/-2.1%;
      2012-2013: 58.6%+/-1.9%) and AI/AN children (2011-2012: 54.4%+/-11.3%; 2012-2013:
      54.6%+/-7.0%). Significant differences in vaccination coverage among VFC-entitled
      and privately insured children were observed within some subgroups of
      race/ethnicity, income, age, region, and living in a metropolitan statistical
      area principle city. CONCLUSIONS: Although finding few differences in influenza
      vaccination coverage among VFC-entitled versus privately insured children was
      encouraging, nearly half of all children were not vaccinated for influenza and
      coverage was particularly low among uninsured children. Additional public health
      interventions are needed to ensure that more children are vaccinated such as a
      strong recommendation from health care providers, utilization of immunization
      information systems, provider reminders, standing orders, and community-based
      interventions such as educational activities and expanded access to vaccination
      services.

PMID- 25979805
TI  - Energetics and behaviour: a reply to Careau and Garland.

PMID- 25979806
TI  - Transport of defense compounds from source to sink: lessons learned from
      glucosinolates.
AB  - Plants synthesize a plethora of defense compounds crucial for their survival in a
      challenging and changing environment. Transport processes are important for
      shaping the distribution pattern of defense compounds, albeit focus hitherto has
      been mostly on their biosynthetic pathways. A recent identification of two
      glucosinolate transporters represents a breakthrough in our understanding of
      glucosinolate transport in Arabidopsis and has advanced knowledge in transport of
      defense compounds. In this review, we discuss the role of the glucosinolate
      transporters in establishing dynamic glucosinolate distribution patterns and
      source-sink relations. We focus on lessons learned from glucosinolate transport
      that may apply to transport of other defense compounds and discuss future avenues
      in the emerging field of defense compound transport.

PMID- 25979807
TI  - [When La Presse Medicale published the medical thesis of Louis Ferdinand Celine
      ... was it partially censured?].

PMID- 25979808
TI  - Effect of gamma-irradiation on structure and physico-chemical properties of
      Amorphophallus paeoniifolius starch.
AB  - Gamma irradiation is one of the effective techniques able to alter structure and
      its properties of starch. In this research, the effect of modification in terms
      of molecular structure and physico-chemical properties of Amorphophallus
      paeoniifolius starch by gamma-irradiation using (60)Co as gamma-source at doses
      of 5, 10, 15, 20 and 25 kGy with dose rate 2 kGy/h was studied. Morphology of
      native and irradiated starches under scanning electron microscope revealed that
      granules are round, elliptical and polygonal in shape with smooth surfaces; no
      cracking or roughness was noted on irradiated starches. Amylose content, pH,
      swelling power of the starches and syneresis of the gelatinized starch were
      significantly decreased by irradiation; while carboxyl content, solubility, light
      transmittance and water absorption capacity of the starch granules were raised
      with increased dose of irradiation. Reduced pasting parameters and changes in
      FTIR spectrum significantly differed from each other. XRD pattern of irradiated
      starches showed C-type pattern with intermediate peaks of 2theta at 16.92 degrees
      and 18.12 degrees , strong peaks of 2theta at 23.05 degrees  and weak peaks of
      2theta at 14.7 degrees , displaying slight decreased in the intensity of peaks in
      irradiated starches. Irradiation of starches increased gelatinization
      temperatures and enthalpy value was measured using DSC.

PMID- 25979809
TI  - CLSI-based transference of CALIPER pediatric reference intervals to Beckman
      Coulter AU biochemical assays.
AB  - OBJECTIVE: The CALIPER program has established a comprehensive database of
      pediatric reference intervals using largely the Abbott ARCHITECT biochemical
      assays. To expand clinical application of CALIPER reference standards, the
      present study is aimed at transferring CALIPER reference intervals from the
      Abbott ARCHITECT to Beckman Coulter AU assays. DESIGN AND METHODS: Transference
      of CALIPER reference intervals was performed based on the CLSI guidelines C28-A3
      and EP9-A2. The new reference intervals were directly verified using up to 100
      reference samples from the healthy CALIPER cohort. RESULTS: We found a strong
      correlation between Abbott ARCHITECT and Beckman Coulter AU biochemical assays,
      allowing the transference of the vast majority (94%; 30 out of 32 assays) of
      CALIPER reference intervals previously established using Abbott assays.
      Transferred reference intervals were, in general, similar to previously published
      CALIPER reference intervals, with some exceptions. Most of the transferred
      reference intervals were sex-specific and were verified using healthy reference
      samples from the CALIPER biobank based on CLSI criteria. It is important to note
      that the comparisons performed between the Abbott and Beckman Coulter assays make
      no assumptions as to assay accuracy or which system is more correct/accurate.
      CONCLUSION: The majority of CALIPER reference intervals were transferrable to
      Beckman Coulter AU assays, allowing the establishment of a new database of
      pediatric reference intervals. This further expands the utility of the CALIPER
      database to clinical laboratories using the AU assays; however, each laboratory
      should validate these intervals for their analytical platform and local
      population as recommended by the CLSI.

PMID- 25979810
TI  - gammadelta T cell activation by bispecific antibodies.
AB  - Bispecific antibodies have been successfully introduced into clinical
      application. gammadelta T cells are of special interest for tumor immunotherapy,
      due to their recognition of pyrophosphates that are overproduced by many tumor
      cells resulting in HLA-nonrestricted tumor cell killing. Here we describe in
      detail a [(Her2)2 * Vgamma9] tribody construct that targets human Vgamma9 T cells
      to HER2-expressing tumor cells. The direct comparison with other selective
      Vgamma9 T cell agonists including phosphoantigens and nitrogen-containing
      bisphosphonates revealed the superiority of the [(Her2)2 * Vgamma9] tribody in
      triggering gammadelta T cell-mediated tumor cell killing with negligible
      induction of gammadelta T cell death. In contrast, phosphoantigens and
      bisphosphonates are potent inducers of gammadelta T cell proliferation but less
      efficient enhancers of gammadelta T cell-mediated tumor cell killing.
      Collectively, our data identify unique properties of a gammadelta T cell
      targeting [(Her2)2 * Vgamma9] tribody which make it an attractive candidate for
      clinical application in gammadelta T cell-based tumor immunotherapy.

PMID- 25979811
TI  - Marine neustonic microplastics around the southeastern coast of Korea.
AB  - We investigated floating debris around the mouth of the Nakdong River in the
      Southeastern Sea of Korea using a Manta trawl (330-MUm mesh) and hand-net (50
      MUm) before (May) and after (July) the rainy season in 2012. Microplastic (<2 mm)
      was present at all of the stations, whereas Styrofoam (2-5 mm) peaked only at a
      few stations far from the Nakdong River mouth in July. The dominant types were
      fibers (polyester), hard plastic (polyethylene), paint particles (alkyd), and
      Styrofoam (expanded polystyrene). The average abundances of fibers and hard
      plastic (<2 mm) in the trawl were significantly higher in July than in May
      (p<0.005, p<0.05, respectively), while two orders of magnitude more microplastics
      (<2 mm) were collected with the hand-net than with the trawl. Fibers and hard
      plastic by trawl were significantly compared temporally, and the hand-net proved
      the missed microplastics (50-330 MUm) when trawl used.

PMID- 25979812
TI  - The effects of coastal development on sponge abundance, diversity, and community
      composition on Jamaican coral reefs.
AB  - Over the past decade, development along the northern coast of Jamaica has
      accelerated, resulting in elevated levels of sedimentation on adjacent reefs. To
      understand the effects of this development on sponge community dynamics, we
      conducted surveys at three locations with varying degrees of adjacent coastal
      development to quantify species richness, abundance and diversity at two depths
      (8-10 m and 15-18 m). Sediment accumulation rate, total suspended solids and
      other water quality parameters were also quantified. The sponge community at the
      location with the least coastal development and anthropogenic influence was often
      significantly different from the other two locations, and exhibited higher sponge
      abundance, richness, and diversity. Sponge community composition and size
      distribution were statistically different among locations. This study provides
      correlative evidence that coastal development affects aspects of sponge community
      ecology, although the precise mechanisms are still unclear.

PMID- 25979813
TI  - Inflammatory reaction after traumatic brain injury: therapeutic potential of
      targeting cell-cell communication by chemokines.
AB  - Traumatic brain injury (TBI) affects millions of people worldwide every year. The
      primary impact initiates the secretion of pro- and anti-inflammatory factors,
      subsequent recruitment of peripheral immune cells, and activation of brain
      resident microglia and astrocytes. Chemokines are major mediators of peripheral
      blood cell recruitment to damaged tissue, including the TBI brain. Here we review
      the involvement of specific chemokine pathways in TBI pathology and attempts to
      modulate these pathways for therapeutic purposes. We focus on chemokine (C-C
      motif) ligand 2/chemokine (C-C motif) receptor 2 (CCL2/CCR2) and chemokine (C-X-C
      motif) ligand 12/chemokine (C-X-C motif) receptor 4 (CXCL12/CXCR4). Recent
      microarray and multiplex expression profiling have also implicated CXCL10 and
      CCL5 in TBI pathology. Chemokine (C-X3-C motif) ligand 1/chemokine (C-X3-C motif)
      receptor 1 (CX3CL1/CX3CR1) signaling in the context of TBI is also discussed.
      Current literature suggests that modulating chemokine signaling, especially
      CCL2/CCR2, may be beneficial in TBI treatment. 

PMID- 25979814
TI  - High-fat diet induced obesity primes inflammation in adipose tissue prior to
      liver in C57BL/6j mice.
AB  - Metabolic inflammation in adipose tissue and the liver is frequently observed as
      a result of diet-induced obesity in human and rodent studies. Although the
      adipose tissue and the liver are both prone to become chronically inflamed with
      prolonged obesity, their individual contribution to the development of metabolic
      inflammation remains speculative. Thus, we aimed to elucidate the sequence of
      inflammatory events in adipose and hepatic tissues to determine their
      contribution to the development of metabolic inflammation and insulin resistance
      (IR) in diet-induced obesity. To confirm our hypothesis that adipose tissue (AT)
      inflammation is initiated prior to hepatic inflammation, C57BL/6J male mice were
      fed a low-fat diet (LFD; 10% kcal fat) or high-fat diet (HFD; 45% kcal fat) for
      either 24, 40 or 52 weeks. Lipid accumulation and inflammation was measured in AT
      and liver. Glucose tolerance was assessed and plasma levels of glucose, insulin,
      leptin and adiponectin were measured at various time points throughout the study.
      With HFD, C57BL/6j mice developed a progressive obese phenotype, accompanied by
      IR at 24 and 40 weeks of HFD, but IR was attenuated after 52 weeks of HFD. AT
      inflammation was present after 24 weeks of HFD, as indicated by the increased
      presence of crown-like structures and up-regulation of pro-inflammatory genes
      Tnf, Il1beta, Mcp1 and F4/80. As hepatic inflammation was not detected until 40
      weeks of HFD, we show that AT inflammation is established prior to the
      development of hepatic inflammation. Thus, AT inflammation is likely to have a
      greater contribution to the development of IR compared to hepatic inflammation.

PMID- 25979815
TI  - Endosonography-related mortality and morbidity for pulmonary indications: a
      nationwide survey in the Netherlands.
AB  - BACKGROUND: Endosonography is being implemented rapidly in pulmonary medicine for
      the diagnosis and staging of lung cancer, the assessment of sarcoidosis, and the
      assessment of mediastinal lesions. Although serious adverse events (SAEs) have
      been described, safety data outside cohort studies are scarce. OBJECTIVE: To
      assess the SAE and mortality rate of EUS-guided FNA (EUS-FNA) and endobronchial
      ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal
      and/or hilar analysis. DESIGN: Nationwide, retrospective survey by using
      questionnaires. SETTING: All hospitals in the Netherlands. PATIENTS: All patients
      undergoing EUS-FNA and EBUS-TBNA for intrathoracic analysis in the period 1999 to
      2011. INTERVENTIONS: EUS-FNA and EBUS-TBNA. MAIN OUTCOME MEASUREMENTS: Occurrence
      of fatal outcomes and SAEs. Detailed information was obtained for each reported
      case, and all cases were reviewed independently by 2 investigators, including
      identification of risk factors. RESULTS: All 89 hospitals (100%) responded. An
      estimated 14,075 EUS-FNA and 2675 EBUS procedures were performed. Seven patients
      died after endosonography (5 EUS-FNA, 2 EBUS [mortality rate 0.04%]). All
      fatalities occurred in patients of poor performance status (American Society of
      Anesthesiologists Physical Status Classification System score of III/IV). Twenty
      five SAEs were reported (22 EUS-FNA, 3 EBUS [SAE rate of 0.15%; EUS-FNA 0.16%,
      EBUS 0.11%]). SAEs were mostly (64%) of infectious origin. No specific risk
      factors for infectious adverse events could be identified. LIMITATIONS:
      Retrospective study, possible recall bias, overrepresentation of EUS-FNA cases.
      CONCLUSION: Endosonography appears to be a safe technique for the analysis of
      mediastinal and/or hilar lesions. Poor performance status is a risk factor for
      fatal outcomes. Mediastinitis and/or mediastinal abscess formation is rare but is
      a potential and dangerous adverse event of endosonography.

PMID- 25979816
TI  - EUS-guided transgastric drainage of a peripancreatic collection containing an
      arterial bypass graft.

PMID- 25979817
TI  - Right ventricular septal pacing in patients with right bundle branch block.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to improve
      left ventricular (LV) function and exercise performance in patients with left
      bundle branch block. Patients with right bundle branch block (RBBB) do not have a
      similar positive response to standard CRT. We hypothesized that single site
      pacing of the right ventricular septum (RVS) near the proximal right bundle could
      restore more normal activation of the LV in RBBB patients. METHODS: 78
      consecutive patients (56 M, 22 F) with baseline RBBB underwent pacemaker or ICD
      implantation. Leads were placed in the right atrium and RVS. RESULTS: Baseline
      QRS duration was 120-220 ms (mean QRSd = 147 ms). At the optimal AV delay, the
      fused QRSd was 56-160 ms (mean QRSd = 112 ms). The mean decrease in QRSd was 34
      +/- 20.4 ms (p<0.001). CONCLUSION: RVS pacing in patients with RBBB resulted in a
      marked decrease in QRS duration and often normalized the ECG.

PMID- 25979818
TI  - Pioneer translation products as an alternative source for MHC-I antigenic
      peptides.
AB  - The notion that alternative peptide substrates can be processed and presented to
      the MHC class I pathway has opened for new aspects on how the immune system
      detects infected or damaged cells. Recent works show that antigenic peptides are
      derived from intron sequences in pre-mRNAs target for the nonsense-mediated
      degradation pathway. Introns are spliced out co-transcriptionally suggesting that
      such pioneer translation products (PTPs) are synthesized on the nascent RNAs in
      the nuclear compartment to ensure that the first peptides to emerge from an mRNA
      are destined for the class I pathway. This illustrates an independent translation
      event during mRNA maturation that give rise to specific peptide products with a
      specific function in the immune system. The characterization of the translation
      apparatus responsible for PTP synthesis will pave the way for understanding how
      PTP production is regulated in different tissues under different conditions and
      will help designing new vaccine strategies. 

PMID- 25979819
TI  - Prevalence of dental disorders in an abattoir population of horses in South
      Africa by oral examination of intact and bisected heads.
AB  - Dental care is an integral part of equine veterinary practice. The objectives of
      this cross sectional study were to describe the prevalence of dental disorders in
      an abattoir population of horses, and to compare oral examination of intact and
      bisected heads. Heads from 40 horses, 19 males and 21 females, were examined and
      divided into immature, adult or older horses based on dental age. Older horses
      had a significantly higher prevalence of infundibular caries (91.7%), diastemata
      (66.7%) and fractures (58.3%), whereas dental wear disorders affected all age
      groups. Gasterophilus spp. larvae were detected in 20% of the horses. A short
      oral examination performed on intact heads was adequate for diagnosing major
      disorders, but the occurrence of many conditions had only fair to poor agreement
      with the bisected heads. A more detailed oral examination may be needed for
      reliable diagnosis of many disorders. 

PMID- 25979820
TI  - Proteomics and autoimmune kidney disease.
AB  - Proteomics has long been considered an ideal platform, and urine an ideal source
      for biomarker discovery in human autoimmune kidney diseases. A number of studies
      have examined the urine proteome to identify biomarkers of disease activity,
      kidney pathology, and response to therapy. Increasingly, proteomic studies of
      kidney disease have expanded to include blood, circulating cells and kidney
      tissue. Recently the clinical potential of renal proteomics has been realized
      through a handful of investigations whose results appear to be applicable to
      patient care. In this review, approaches to the proteomic evaluation of
      autoimmune kidney diseases will be considered in the context of developing
      clinically useful disease biomarkers. 

PMID- 25979821
TI  - Effects of group housing on ECG assessment in conscious cynomolgus monkeys.
AB  - INTRODUCTION: Assessing the cardiovascular safety of new chemical or biological
      entities is important during pre-clinical development. Electrocardiogram (ECG)
      assessments in non-human primate (NHP) toxicology studies are often made using
      non-invasive telemetry systems. We investigated whether ECG recording was
      feasible during group housing of NHPs, rather than the usual single housed
      arrangement, and whether it would impact the data collected or affect the ability
      to detect drug-induced changes in QTc interval. METHODS: Following a period of
      acclimatisation to jackets, cynomolgus monkeys (3 males and 3 females) were
      housed in same sex groups of 3. Female monkeys were administered 4 doses of
      vehicle while male monkeys were administered vehicle, 15, 45, and 135mg/kg
      moxifloxacin. Each dose was administered on a separate dosing day. The same
      dosing protocol was repeated with the animals singly housed and the results from
      the two phases were compared including assessment of statistical power. RESULTS:
      Heart rate (HR) was significantly lower, and PR and QT intervals were
      significantly higher, at multiple time points when the animals were group housed
      compared with the singly housed phase. QRS duration and QTc interval were less
      affected. Moxifloxacin increased QT and QTc intervals but had no consistent
      effect on HR, QRS duration or PR interval under group housed or singly housed
      conditions. Power analysis suggested that group housing did not adversely affect
      the magnitude of detectable changes of ECG parameters. In general, detection of
      slightly smaller changes was achieved under conditions of group housing.
      DISCUSSION: The current study shows group housing to be technically possible
      during non-invasive ECG recording, resulting in lower resting heart rates and
      small improvements in sensitivity of detection of drug-induced effects. Given the
      psychological benefits of group housing for NHPs, it is a refinement that should
      be considered when conducting ECG assessments in NHP toxicology studies.

PMID- 25979822
TI  - Cyclosporine-related brainstem atypical posterior reversible leukoencephalopathy
      syndrome following hematopoietic stem cell transplant.

PMID- 25979823
TI  - Capturing Between- and Within-Family Differences in Parental Support to Adult
      Children: A Typology Approach.
AB  - OBJECTIVES: Families differ widely in the support they provide to adult
      offspring, both with regard to the overall level as well as the extent to which
      support is evenly distributed across offspring. This study addressed these
      dynamics by creating family profiles based on the average level and
      differentiation of support among children. We also examined demographic and
      psychological factors that predict typology membership. METHOD: We utilized data
      from 431 middle-aged parents (aged 40-60) with at least two adult children.
      Parents provided separate ratings of support given to each child. Latent profile
      analysis was applied to two indicators of within-family support: mean level and
      differentiation among offspring. RESULTS: Latent profile analysis identified four
      patterns of parental support: (a) high support-low differentiation (52%), (b)
      medium support-high differentiation (26%), (c) low support-low differentiation
      (17%), and (d) low support-very high differentiation (5%). These patterns
      reflected distinct family characteristics, such as parental resources, parental
      beliefs (i.e., equal treatment, obligation), and offspring characteristics.
      DISCUSSION: Our findings emphasize the need to capture dynamics of support
      exchanges among multiple offspring at the level of family.

PMID- 25979824
TI  - Failure of fixed orthodontic retainers: A systematic review.
AB  - OBJECTIVE: To evaluate the risk of failure of fixed orthodontic retention
      protocols. DATA: Screening for inclusion eligibility, quality assessment of
      studies and data extraction was performed independently by two authors. SOURCES:
      The electronic databases MEDLINE, EMBASE and CENTRAL were searched with no
      restrictions on publication date or language using detailed strategies. The main
      outcome assessed was bond failure. STUDY SELECTION: Twenty-seven studies
      satisfied the inclusion criteria. Randomised controlled trials and prospective
      studies were evaluated according to the Cochrane risk of bias tool. Retrospective
      studies were graded employing the predetermined criteria of Bondemark. RESULTS:
      Nine randomised controlled trials, four of which were of low quality, were
      identified. Six studies had a prospective design and all were of low quality.
      Twelve studies were retrospective. The quality of trial reporting was poor in
      general. Four studies assessing glass-fibre retainers, three RCTs and one
      prospective, reported bond failures from 11 to 71%, whereas twenty studies
      evaluating multistranded retainers - nine RCTs, two prospective and nine
      retrospective - reported failures ranging from 12 to 50%. One comparison was
      performed, multistranded wires vs. polyehtylene woven ribbon (RR: 1.74; 95% CI:
      0.45, 6.73; p=0.42). CONCLUSION: The quality of the available evidence is low. No
      conclusive evidence was found in order to guide orthodontists in the selection of
      the best protocol. CLINICAL SIGNIFICANCE: Although fixed orthodontic retainers
      have been used for years in clinical practice, the selection of the best
      treatment protocol still remains a subjective issue. The available studies, and
      their synthesis, cannot provide reliable evidence in this field.

PMID- 25979825
TI  - The effect of benzalkonium chloride additions to AH Plus sealer. Antimicrobial,
      physical and chemical properties.
AB  - OBJECTIVES: The aim of this study was to determine the antimicrobial and
      antibiofilm activities and physicochemical properties of AH Plus sealer mixed
      with different concentrations of benzalkonium chloride (BC). METHODS: AH Plus was
      tested alone and mixed with 1%, 2% and 3% of BC. The antimicrobial and
      antibiofilm activities of the sealers against Enterococcus faecalis were
      evaluated by the direct contact test (DCT) and by confocal laser scanning
      microscopy, respectively. Setting time, flow and solubility were assessed
      according to ANSI/ADA specifications. Microhardness and contact angle tests were
      also performed. The chemical changes of the sealers were evaluated by X-ray
      diffraction analysis, and both Fourier transform infrared spectroscopy (FT-IR)
      and attenuated total reflectance Fourier transform infrared (ATR FT-IR). RESULTS:
      AH Plus+3% BC was the only sealer to promote total elimination of E. faecalis and
      the biovolume in this group was significantly lower than in the rest of the
      sealers (p>0.05). The physical properties of the sealers were according to the
      ANSI/ADA specifications. The microhardness decreased significantly when BC was
      added and a significant reduction in contact angle was obtained when
      incorporating 2% and 3% BC (p<0.05). No phase changes were observed with the
      modified sealers. CONCLUSIONS: The addition of 2% or higher concentrations BC to
      AH Plus showed antimicrobial and antibiofilm activities without affecting the
      properties specified in ANSI/ADA standards. However, additives to the root canal
      sealer altered other physical and chemical properties that are not commonly found
      in the literature to evaluate filling materials. CLINICAL SIGNIFICANCE: The
      present study highlights that the antimicrobial properties of AH Plus can be
      significantly improved with the addition of BC. Testing beyond what is specified
      in standards may be indicated.

PMID- 25979826
TI  - The translation factor eIF5A and human cancer.
AB  - The eukaryotic initiation factor eIF5A is a translation factor that, unusually,
      has been assigned functions in both initiation and elongation. Additionally, it
      is implicated in transcription, mRNA turnover and nucleocytoplasmic transport.
      Two eIF5A isoforms are generated from distinct but related genes. The major
      isoform, eIF5A1, is considered constitutive, is abundantly expressed in most
      cells, and is essential for cell proliferation. The second isoform, eIF5A2, is
      expressed in few normal tissues but is highly expressed in many cancers and has
      been designated a candidate oncogene. Elevated expression of either isoform
      carries unfavorable prognostic implications for several cancers, and both have
      been advanced as cancer biomarkers. The amino acid hypusine, a presumptively
      unique eIF5A post-translational modification, is required for most known eIF5A
      functions and it renders eIF5A susceptible to inhibitors of the modification
      pathway as therapeutic targets. eIF5A has been shown to regulate a number of gene
      products specifically, termed the eIF5A regulon, and its role in translating
      proline-rich sequences has recently been identified. A model is advanced that
      accommodates eIF5A in both the initiation and elongation phases of translation.
      We review here the biochemical functions of eIF5A, the relationship of its
      isoforms with human cancer, and evolving clinical applications. This article is
      part of a Special Issue entitled: Translation and Cancer. 

PMID- 25979827
TI  - Reciprocal regulation of amino acid import and epigenetic state through Lat1 and
      EZH2.
AB  - Lat1 (SLC7A5) is an amino acid transporter often required for tumor cell import
      of essential amino acids (AA) including Methionine (Met). Met is the obligate
      precursor of S-adenosylmethionine (SAM), the methyl donor utilized by all
      methyltransferases including the polycomb repressor complex (PRC2)-specific EZH2.
      Cell populations sorted for surface Lat1 exhibit activated EZH2, enrichment for
      Met-cycle intermediates, and aggressive tumor growth in mice. In agreement, EZH2
      and Lat1 expression are co-regulated in models of cancer cell differentiation and
      co-expression is observed at the invasive front of human lung tumors. EZH2
      knockdown or small-molecule inhibition leads to de-repression of RXRalpha
      resulting in reduced Lat1 expression. Our results describe a Lat1-EZH2 positive
      feedback loop illustrated by AA depletion or Lat1 knockdown resulting in SAM
      reduction and concomitant reduction in EZH2 activity. shRNA-mediated knockdown of
      Lat1 results in tumor growth inhibition and points to Lat1 as a potential
      therapeutic target. 

PMID- 25979829
TI  - Foreword.

PMID- 25979828
TI  - TUT7 controls the fate of precursor microRNAs by using three different
      uridylation mechanisms.
AB  - Terminal uridylyl transferases (TUTs) function as integral regulators of microRNA
      (miRNA) biogenesis. Using biochemistry, single-molecule, and deep sequencing
      techniques, we here investigate the mechanism by which human TUT7 (also known as
      ZCCHC6) recognizes and uridylates precursor miRNAs (pre-miRNAs) in the absence of
      Lin28. We find that the overhang of a pre-miRNA is the key structural element
      that is recognized by TUT7 and its paralogues, TUT4 (ZCCHC11) and TUT2
      (GLD2/PAPD4). For group II pre-miRNAs, which have a 1-nt 3' overhang, TUT7
      restores the canonical end structure (2-nt 3' overhang) through mono-uridylation,
      thereby promoting miRNA biogenesis. For pre-miRNAs where the 3' end is further
      recessed into the stem (as in 3' trimmed pre-miRNAs), TUT7 generates an oligo-U
      tail that leads to degradation. In contrast to Lin28-stimulated oligo
      uridylation, which is processive, a distributive mode is employed by TUT7 for
      both mono- and oligo-uridylation in the absence of Lin28. The overhang length
      dictates the frequency (but not duration) of the TUT7-RNA interaction, thus
      explaining how TUT7 differentiates pre-miRNA species with different overhangs.
      Our study reveals dual roles and mechanisms of uridylation in repair and removal
      of defective pre-miRNAs.

PMID- 25979830
TI  - Surgical and concomitant epicardial-endocardial (hybrid) ablation of persistent
      and long-standing persistent atrial fibrillation.
AB  - Catheter ablation of atrial fibrillation (AF) has been shown to be effective for
      paroxysmal AF. However, for patients with persistent or longstanding persistent
      AF, the success rates for catheter ablation is low. The Cox-Maze procedure is the
      most effective non-pharmacological treatment of AF. However, due to the need for
      open-heart surgery and the morbidity associated with the surgical Cox-Maze
      procedure, minimally invasive and epicardial-endocardial (hybrid) ablation
      procedures have been developed. This article will review the main surgical and
      hybrid approaches used for the treatment of persistent and long-standing
      persistent AF. 

PMID- 25979831
TI  - BRAF p.V600E immunohistochemistry in challenging samples: about false-positive
      and false-negative results.

PMID- 25979832
TI  - A daunting challenge: Human Papillomavirus assays and cytology in primary
      cervical screening of women below age 30years.
AB  - We compared cytology with Hybrid Capture 2 (HC2), cobas, CLART and APTIMA Human
      Papillomavirus (HPV) assays in primary cervical screening at age 23-29 years
      based on data from the Danish Horizon study. SurePath samples were collected from
      1278 women undergoing routine cytology-based screening. Abnormal cytology was
      managed according to the routine recommendations, and women with cytology
      normal/HPV-positive samples were invited for repeated cytology and HPV testing in
      1.5 years. Loss to follow-up was similar between HPV assays. ? CIN3 was detected
      in 44 women. The sensitivity of HC2 for ? CIN3 was 95% (95% confidence interval
      (CI): 85-99), of cobas 98% (95% CI: 88-100), of CLART 100% (95% CI: 92-100), of
      APTIMA 82% (95% CI: 67-92), and of cytology 59% (95% CI: 43-74). Specificity for
      ? CIN3 varied between 61% (95% CI: 59-64) for cobas and 75% (95% CI: 73-78) for
      APTIMA, and was 94% (95% CI: 93-96) for cytology. Similar results were observed
      for ? CIN2 (N = 68). HPV screening with cytological triage doubled the number of
      colposcopies compared to cytology screening, and increased the frequency of
      repeated testing by four (APTIMA) to seven (cobas) times. The positive predictive
      value of a referral for colposcopy was relatively high for all screening tests (?
      30% for ? CIN3, and ? 50% for ? CIN2). CIN1 was detected by cytology in ~ 1% of
      women, and in ~ 2% by any of the four HPV assays. Although highly sensitive, HPV
      based screening of young Danish women should be approached cautiously, as it
      resulted in large reductions in specificity, and increased the demand for
      additional testing.

PMID- 25979833
TI  - Location of colon cancer (right-sided versus left-sided) as a prognostic factor
      and a predictor of benefit from cetuximab in NCIC CO.17.
AB  - BACKGROUND: Right- and left-sided colon cancers (RC, LC) differ with respect to
      biology, pathology and epidemiology. Previous data suggest a mortality difference
      between RC and LC. We examined if primary tumour side also predicts for outcome
      in chemotherapy refractory, metastatic colon cancer (MCC). We also compared RC
      versus LC as a predictor of efficacy of epidermal growth factor receptor (EGFR)
      inhibition with cetuximab. METHODS: Reanalyzing NCIC CO.17 trial (cetuximab
      versus best supportive care [BSC]), we coded the primary tumour side as RC
      (caecum to transverse colon) or LC (splenic flexure to rectosigmoid). The
      association between tumour side and baseline characteristics was assessed. Cox
      regression models determined factors affecting overall survival (OS) and
      progression free survival (PFS). RESULTS: Patients with RC (150/399) had more
      poorly differentiated, mutant KRAS, mutated PIK3CA and wild-type BRAF tumours,
      fewer liver and lung metastases, and shorter interval between diagnosis and study
      entry. Among BSC patients, tumour side was not prognostic for PFS (hazard ratios
      (HR) 1.07 [0.79-1.44], p = 0.67) or OS (HR 0.96 [0.70-1.31], p = 0.78). Among
      wild-type KRAS patients, those with LC had significantly improved PFS when
      treated with cetuximab compared to BSC (median 5.4 versus 1.8 months, HR 0.28
      [0.18-0.45], p < 0.0001), whereas those with RC did not (median 1.9 versus 1.9
      months, HR 0.73 [0.42-1.27], p = 0.26), [interaction p = 0.002]. CONCLUSION: In
      refractory MCC, tumour location within the colon is not prognostic, but is
      strongly predictive of PFS benefit from cetuximab therapy. Additional research is
      needed to understand the molecular differences between RC and LC and their
      interaction with EGFR inhibition.

PMID- 25979834
TI  - Echocardiographic Chamber Quantification in the Era of Multimodality Imaging:
      Beware of Unintended Consequences.

PMID- 25979835
TI  - Ebola vaccine trial in west Africa faces criticism.

PMID- 25979837
TI  - Mitochondrial degradation and energy metabolism.
AB  - Mitochondria are intracellular power plants that feed most eukaryotic cells with
      the ATP produced by the oxidative phosphorylation (OXPHOS). Mitochondrial energy
      production is controlled by many regulatory mechanisms. The control of
      mitochondrial mass through both mitochondrial biogenesis and degradation has been
      proposed to be one of the most important regulatory mechanisms. Recently,
      autophagic degradation of mitochondria has emerged as an important mechanism
      involved in the regulation of mitochondrial quantity and quality. In this review,
      we highlight the intricate connections between mitochondrial energy metabolism
      and mitochondrial autophagic degradation by showing the importance of
      mitochondrial bioenergetics in this process and illustrating the role of
      mitophagy in mitochondrial patho-physiology. Furthermore, we discuss how energy
      metabolism could coordinate the biogenesis and degradation of this organelle.

PMID- 25979836
TI  - Gastrointestinal hormones/neurotransmitters and growth factors can activate P21
      activated kinase 2 in pancreatic acinar cells by novel mechanisms.
AB  - P-21-activated kinases (PAKs) are serine/threonine kinases comprising six
      isoforms divided in two groups, group-I (PAK1-3)/group-II (PAK4-6) which play
      important roles in cell cytoskeletal dynamics, survival, secretion and
      proliferation and are activated by diverse stimuli. However, little is known
      about PAKs ability to be activated by gastrointestinal (GI)
      hormones/neurotransmitters/growth-factors. We used rat pancreatic acini to
      explore the ability of GI-hormones/neurotransmitters/growth-factors to activate
      Group-I-PAKs and the signaling cascades involved. Only PAK2 was present in acini.
      PAK2 was activated by some pancreatic growth-factors [EGF, PDGF, bFGF], by
      secretagogues activating phospholipase-C (PLC) [CCK, carbachol, bombesin] and by
      post-receptor stimulants activating PKC [TPA], but not agents only mobilizing
      cellular calcium or increasing cyclic AMP. CCK-activation of PAK2 required both
      high- and low-affinity-CCK1-receptor-state activation. It was partially reduced
      by PKC- or Src-inhibition, but not with PI3K-inhibitors (wortmannin, LY294002) or
      thapsigargin. IPA-3, which prevents PAK2 binding to small-GTPases partially
      inhibited PAK2-activation, as well as reduced CCK-induced ERK1/2 activation and
      amylase release induced by CCK or bombesin. This study demonstrates pancreatic
      acini, possess only one Group-I-PAK, PAK2. CCK and other GI
      hormones/neurotransmitters/growth-factors activate PAK2 via small GTPases
      (CDC42/Rac1), PKC and SFK but not cytosolic calcium or PI3K. CCK-activation of
      PAK2 showed several novel features being dependent on both receptor-activation
      states, having PLC- and PKC-dependent/independent components and small-GTPase
      dependent/independent components. These results show that PAK2 is important in
      signaling cascades activated by numerous pancreatic stimuli which mediate their
      various physiological/pathophysiological responses and thus could be a promising
      target for the development of therapies in some pancreatic disorders such as
      pancreatitis. 

PMID- 25979838
TI  - Treatment of Chronic Facial Pain Including Cluster Headache by Repetitive
      Transcranial Magnetic Stimulation of the Motor Cortex With Maintenance Sessions:
      A Naturalistic Study.
AB  - OBJECTIVE: To assess the long-term maintenance of analgesia induced by high
      frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex
      contralateral to pain in a naturalistic study of patients with chronic refractory
      facial pain. METHODS: 55 patients were included (cluster headache, n = 19;
      trigeminal neuropathic pain, n = 21; atypical facial pain, n = 15). The rTMS
      protocol consisted of an "induction phase" of one daily rTMS session for five
      days per week during two consecutive weeks, followed by a "maintenance phase" of
      two sessions during one week, then one session in weeks 4 and 6, and a monthly
      session for the next five months. In a subset of patients, navigated targeting
      was performed and session duration was shortened from 20-min to 10-min (with the
      same number of 2000 pulses per session). The analgesic effect of rTMS was
      assessed on a 0-10 visual numerical scale from 15 to 180 days after treatment
      initiation. RESULTS: All pain measures significantly decreased from baseline to
      D15: the intensity of permanent pain (5.2 +/- 1.6 to 3.2 +/- 1.9) and paroxysmal
      pain (8.6 +/- 1.5 to 4.5 +/- 3.4), as well as the daily number of painful attacks
      (5.6 +/- 3.1 to 2.3 +/- 3.1). The percentage of responders (defined as pain score
      decrease >=30%) was 73% at D15 and dropped to 40% at D180. The analgesic effect
      was similar regardless of the type of pain and was significantly lower when
      session duration was shortened, irrespective of the number of pulses. CONCLUSION:
      This long-term maintenance rTMS protocol can be a therapeutic option in the
      clinical management of patients with chronic refractory facial pain, including
      cluster headache. However, only part of the patients respond to this technique
      and session duration should not be reduced.

PMID- 25979839
TI  - Transcranial Direct Current Stimulation Against Sudden Unexpected Death in
      Epilepsy: Press That Button Again, Please.

PMID- 25979840
TI  - Isometric exercise induces analgesia and reduces inhibition in patellar
      tendinopathy.
AB  - BACKGROUND: Few interventions reduce patellar tendinopathy (PT) pain in the short
      term. Eccentric exercises are painful and have limited effectiveness during the
      competitive season. Isometric and isotonic muscle contractions may have an
      immediate effect on PT pain. METHODS: This single-blinded, randomised cross-over
      study compared immediate and 45 min effects following a bout of isometric and
      isotonic muscle contractions. Outcome measures were PT pain during the single-leg
      decline squat (SLDS, 0-10), quadriceps strength on maximal voluntary isometric
      contraction (MVIC), and measures of corticospinal excitability and inhibition.
      Data were analysed using a split-plot in time-repeated measures analysis of
      variance (ANOVA). RESULTS: 6 volleyball players with PT participated. Condition
      effects were detected with greater pain relief immediately from isometric
      contractions: isometric contractions reduced SLDS (mean+/-SD) from 7.0+/-2.04 to
      0.17+/-0.41, and isotonic contractions reduced SLDS (mean+/-SD) from 6.33+/-2.80
      to 3.75+/-3.28 (p<0.001). Isometric contractions released cortical inhibition
      (ratio mean+/-SD) from 27.53%+/-8.30 to 54.95%+/-5.47, but isotonic contractions
      had no significant effect on inhibition (pre 30.26+/-3.89, post 31.92+/-4.67;
      p=0.004). Condition by time analysis showed pain reduction was sustained at 45
      min postisometric but not isotonic condition (p<0.001). The mean reduction in
      pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic. MVIC
      increased significantly following the isometric condition by 18.7+/-7.8%, and was
      significantly higher than baseline (p<0.001) and isotonic condition (p<0.001),
      and at 45 min (p<0.001). CONCLUSIONS: A single resistance training bout of
      isometric contractions reduced tendon pain immediately for at least 45 min
      postintervention and increased MVIC. The reduction in pain was paralleled by a
      reduction in cortical inhibition, providing insight into potential mechanisms.
      Isometric contractions can be completed without pain for people with PT. The
      clinical implications are that isometric muscle contractions may be used to
      reduce pain in people with PT without a reduction in muscle strength.

PMID- 25979843
TI  - A rare case of Cushing's syndrome in pregnancy.

PMID- 25979841
TI  - High prevalence and diversity of bovine astroviruses in the faeces of healthy and
      diarrhoeic calves in South West Scotland.
AB  - Astroviruses (AstV) are single-stranded, positive-sense RNA viruses and one of
      the major causes of infant diarrhoea worldwide. Diarrhoea is a common and
      important cause of morbidity and mortality in calves; therefore, we investigated
      whether the presence of AstV is associated with calf diarrhoea. We identified
      diverse AstV lineages from faecal samples of both healthy and diarrhoeic calves
      and healthy adult cattle in South West Scotland. AstV was common in calves
      (present in 74% (85/115) of samples) but uncommon in adult cattle (present in 15%
      (3/20) of samples). No association was found between the presence of AstV and
      calf diarrhoea or the presence of a specific AstV lineage and calf diarrhoea.
      AstV was strongly associated with the presence of rotavirus Group A (RVA), and a
      protective effect of age was evident for both AstV and RVA. Co-infections with
      multiple AstV lineages were detected in several calves and serial infection with
      different viruses could also be seen by longitudinal sampling of individuals. In
      summary, our study found genotypically diverse AstV in the faeces of calves in
      South West Scotland. However, no association was identified between AstV and calf
      diarrhoea, which suggests the virus does not play a primary role in the aetiology
      of calf diarrhoea in the group studied. 

PMID- 25979842
TI  - CD44 regulates cell proliferation, migration, and invasion via modulation of c
      Src transcription in human breast cancer cells.
AB  - CD44 was recently identified as a cancer initiation marker on the cell membrane.
      The cytoplasmic tail of CD44 is known to bind ERM (ezrin, radixin, moesin)
      proteins, cytoskeletal proteins like ankyrin, and the non-receptor tyrosine
      kinase c-Src. CD44 transmits its oncogenic signaling via c-Src and its downstream
      effectors. To investigate the role of CD44 in breast cancer cells, we generated
      CD44 knock-down cells via retroviral delivery of shRNA against CD44. We found
      that silencing of CD44 decreased the proliferation, migration, and invasion of
      breast cancer cells. The expression and activity of cell migration-related
      proteins, including c-Src, paxillin, and FAK were decreased by CD44 silencing. We
      also found that the c-Jun protein level was negatively regulated via induction of
      a GSK-3beta-dependent degradation pathway in CD44 knock-down cells. The
      expression level of Sp1, a target gene product of c-Jun, was also decreased in
      these cells. Finally, CD44 knock-down suppressed both mRNA and protein levels of
      c-Src and its downstream MAPK pathway as a result of down-regulation of Sp1 as a
      transcription factor for c-Src. Collectively, these results indicate that
      biological changes induced by CD44 silencing are mediated by cumulative down
      regulation of c-Jun, Sp1, and c-Src in human breast cancer cells. 

PMID- 25979844
TI  - Maternal and neonatal outcomes in morbidly adherent placenta: a developing
      country experience.
AB  - BACKGROUND: Morbid adherent placenta, a severe pregnancy complication, is
      associated with massive obstetrical haemorrhage and high maternal mortality.
      Antenatal diagnosis and meticulous multidisciplinary planning at delivery is
      crucial for optimal outcome. We aim to identify the maternal and neonatal outcome
      in women with morbid adherent placenta. METHOD: It was a retrospective evaluation
      of cases of clinically suspected and/or histologically confirmed morbid adherent
      placenta over a 1-year period. RESULTS: The incidence of morbid adherent placenta
      was 1 per 306 deliveries. Previous Caesarean section with placenta praevia was
      the commonest risk factor. Among all, 71.4% had no antenatal care. Of all, 38.9%
      women needed transfer to critical care. There were five (23.8%) maternal deaths.
      Of the 21 neonates, four were stillborn, nine needed NICU transfer and eight had
      an Apgar score of 9 at 5 min of birth. CONCLUSION: Morbid adherent placenta is
      associated with poor maternal and neonatal outcome.

PMID- 25979845
TI  - Leech out of reach: presented with haematuria and urinary retention. [Corrected].

PMID- 25979846
TI  - The established and future biomarkers of malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median
      survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a
      result of historic asbestos exposure in industrialized countries and continued
      use of asbestos in developing countries. Lack of accurate biomarkers makes
      diagnosis, prognostication and treatment prediction of MPM challenging. The aim
      of this review is to identify the front line of MPM biomarkers with current or
      potential clinical impact. Literature search using the PubMed and PLoS One
      databases, the related-articles function of PubMed and the reference lists of
      associated publications until April 26th 2015 revealed a plethora of candidate
      biomarkers. The current gold standard of MPM diagnosis is a combination of two
      positive and two negative immunohistochemical markers in the epithelioid and
      biphasic type, but sarcomatous type do not have specific markers, making
      diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as
      adjuvant diagnostic with high specificity but low sensitivity. Circulating
      proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test,
      transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N
      ERC mesothelin and deformability cytometry may be important future markers.
      Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for
      vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1
      gene are potential markers of MPM susceptibility. In conclusion, the current
      status of MPM biomarkers is not satisfactory but encouraging as more sensitive
      and specific non-invasive markers are emerging. However, prospective validation
      is needed before clinical application. 

PMID- 25979847
TI  - Refractory celiac disease and EATL patients show severe malnutrition and
      malabsorption at diagnosis.
AB  - BACKGROUND & AIMS: Refractory celiac disease type II (RCDII) and EATL
      (Enteropathy Associated T-cell Lymphoma) are (pre)malignant complications of
      celiac disease (CD). Data on malnutrition and intestinal absorption is lacking in
      these patients. Therefore, the aim of the study is to comprehensively assess
      nutritional status and intestinal absorption capacity of patients with RCDII and
      EATL, compared with data of newly diagnosed CD patients. METHODS: Observational
      study in tertiary care setting in RCDII (n = 24, 63.8 +/- 8.2 y), EATL (n = 25,
      62.3 +/- 5.7 y) and CD patients (n = 43, 45.6 +/- 14.8 y). At diagnosis,
      anthropometry (BMI, unintentional weight loss, fat-free mass index (FFMI),
      handgrip strength (HGS), nutritional intake, fecal losses and Resting Energy
      Expenditure (REE)) were assessed. RESULTS: Low BMI (<18.5) was more often
      observed in RCDII patients than in CD or EATL patients (in 33%, 12% and 12%,
      respectively, p = 0.029). EATL patients more frequently had unintentional weight
      loss (>10%) than CD or RCDII patients (in 58%, 19% and 39% of patients,
      respectively; p = 0.005/0.082). Energy malabsorption (<85%) was detected in 44%
      and 33% of RCDII and EATL patients, vs 21.6% in CD (NS). Fecal energy losses were
      higher in RCDII than in CD patients (589 +/- 451 vs 277 +/- 137 kcal/d, p =
      0.017). REE was underestimated by predicted-REE with>10% in 60% of RCDII, 89% of
      EATL, and 38% of CD patients (p = 0.006). Low FFMI and HGS were detected in one
      third and two thirds of all patients, respectively. CONCLUSIONS: The nutritional
      status of patients with RCDII and EATL is inferior compared with untreated naive
      CD patients at presentation. Both malabsorption as well as hypermetabolism
      contribute to malnutrition.

PMID- 25979849
TI  - Neural variability: friend or foe?
AB  - Although we may not realize it, our brain function varies markedly from moment to
      moment such that our brain responses exhibit substantial variability across
      trials even in response to a simple repeating stimulus. Should we care about such
      within-subject variability? Are there developmental, cognitive, and clinical
      consequences to having a brain that is more or less variable/noisy? Although
      neural variability seems to be beneficial for learning, excessive levels of
      neural variability are apparent in individuals with different clinical disorders.
      We propose that measuring distinct types of neural variability in autism and
      other disorders is likely to reveal crucial insights regarding their
      neuropathology. We further discuss the importance of studying neural variability
      more generally across development and aging in humans. 

PMID- 25979848
TI  - The muted sense: neurocognitive limitations of olfactory language.
AB  - Most people find it profoundly difficult to name familiar smells. This difficulty
      persists even when perceptual odor processing and visual object naming are
      unimpaired, implying deficient sensory-specific interactions with the language
      system. Here we synthesize recent behavioral and neuroimaging data to develop a
      biologically informed framework for olfactory lexical processing in the human
      brain. Our central premise is that the difficulty in naming common objects
      through olfactory (compared with visual) stimulation is the end result of
      cumulative effects occurring at three successive stages of the olfactory language
      pathway: object perception, lexical-semantic integration, and verbalization.
      Understanding the neurocognitive mechanisms by which the language network
      interacts with olfaction can yield unique insights into the elusive nature of
      olfactory naming. 

PMID- 25979850
TI  - Significance of objects in the perirhinal cortex.
AB  - The perirhinal cortex is known to play a role in recognition memory and visual
      perception of objects. A recent single-unit recording study adds to our
      understanding of perirhinal cortex function, suggesting that it may also play a
      role in evaluating the significance of objects in a context-dependent manner. 

PMID- 25979852
TI  - The ossification pattern in paediatric occipito-cervical spine: is it possible to
      estimate real age?
AB  - AIM: To retrospectively analyse the synchondrosis from the occipital bone to the
      whole cervical spine and determine the feasibility and validity of age estimation
      using computed tomography (CT) images. MATERIAL AND METHODS: A total of 231
      cervical spine or neck CT images of young children (<7 years of age) were
      examined. Twelve ossification centres were assessed (occiput: n = 2; atlas: n =
      2; axis, n = 6; whole sub-axial vertebra: n = 2), and the ossification process
      was graded as open (O, fully lucent), osseous bridging (B, partially ossified),
      and fusion (F, totally ossified). After the first analysis was completed, the
      resulting chronological chart was used to estimate the age of 10 new cases in
      order to confirm the usefulness of the chart. RESULTS: Infancy was easily
      estimated using the sub-axial or C2 posterior ossification centres, while the
      posterior occipital regions provided good estimation of age between 1-2 years.
      The most difficult period for accurate age estimation was between 2-4 years.
      However, the C2 anterior (neurocentral ossification) and C1 posterior regions did
      yield information to help determine the age around 3 years. The anterior
      occipital region was useful for age estimation between 4-5 years, and the C1
      anterior region was potentially useful to help decide among the other parameters.
      The test for age estimation (TAE) had a very high ICC score (0.973) among the
      three observers. CONCLUSION: Segmentalised analysis can enhance the ability to
      estimate real age, at least by the year. The analysis of the occipital bone made
      a strong contribution to the usefulness of the chorological chart. An organised
      chronological chart can provide readily available information for age estimation,
      and the primary application of the above data (TAE) demonstrated the validity of
      this approach.

PMID- 25979851
TI  - Targeting mechanisms at sites of complement activation for imaging and therapy.
AB  - The complement system plays a key role in many acute injury states as well as
      chronic autoimmune and inflammatory diseases. Localized complement activation and
      alternative pathway-mediated amplification on diverse target surfaces promote
      local recruitment of pro-inflammatory cells and elaboration of other mediators.
      Despite a general understanding of the architecture of the system, though, many
      of the mechanisms that underlie site-specific complement activation and
      amplification in vivo are incompletely understood. In addition, there is no
      capability yet to measure the level of local tissue site-specific complement
      activation in patients without performing biopsies to detect products using
      immunohistochemical techniques. Herein is reviewed emerging evidence obtained
      through clinical research studies of human rheumatoid arthritis along with
      translational studies of its disease models which demonstrate that several
      parallel mechanisms are involved in site-specific amplification of activation of
      the complement system in vivo. Among these processes are de-regulation of the
      alternative pathway, effector pathway-catalyzed amplification of proximal
      complement activation, recognition of injury-associated ligands by components of
      the lectin pathway, and engagement of pathogenic natural antibodies that
      recognize a limited set of injury-associated neoepitopes. Studies suggest that
      each of these inter-related processes can play key roles in amplification of
      complement-dependent injury on self-tissues in vivo. These findings, in addition
      to development of an imaging strategy described herein designed to quantitatively
      measure local complement C3 fixation, have relevance to therapeutic and
      diagnostic strategies targeting the complement system.

PMID- 25979853
TI  - Extravascular complications following abdominal organ transplantation.
AB  - A variety of transplants have been performed in the abdomen including liver,
      kidney, pancreas and islet, bowel, and multivisceral transplants. Imaging plays
      an important role in graft surveillance particularly to exclude post-transplant
      complications. When complications occur, therapeutic image-guided interventions
      are invaluable as these may be graft-saving and even life-saving. Vascular
      complications following transplantation have been extensively reported in recent
      reviews. The focus of this review is to discuss post-transplant complications
      that are primarily extravascular in location. This includes biliary, urological,
      intestinal, malignancy, infections, and miscellaneous complications. Familiarity
      with the imaging appearances of these complications is helpful for radiologists
      as accurate diagnosis and expedient treatment has an impact on graft and patient
      survival. 

PMID- 25979854
TI  - Direct nose-to-brain delivery of lamotrigine following intranasal administration
      to mice.
AB  - Pharmacoresistance is considered one of the major causes underlying the failure
      of the anticonvulsant therapy, demanding the development of alternative and more
      effective therapeutic approaches. Due to the particular anatomical features of
      the nasal cavity, intranasal administration has been explored as a means of
      preferential drug delivery to the brain. The purpose of the present study was to
      assess the pharmacokinetics of lamotrigine administered by the intranasal route
      to mice, and to investigate whether a direct transport of the drug from nose to
      brain could be involved. The high bioavailability achieved for intranasally
      administered lamotrigine (116.5%) underscored the fact that a substantial
      fraction of the drug has been absorbed to the systemic circulation. Nonetheless,
      the heterogeneous biodistribution of lamotrigine in different brain regions, with
      higher concentration levels attained in the olfactory bulb comparatively to the
      frontal cortex and the remaining portion of the brain, strongly suggest that
      lamotrigine was directly transferred to the brain via the olfactory neuronal
      pathway, circumventing the blood-brain barrier. Therefore, it seems that
      intranasal route can be assumed as a suitable and valuable drug delivery strategy
      for the chronic treatment of epilepsy, also providing a promising alternative
      approach for a prospective management of pharmacoresistance. 

PMID- 25979855
TI  - Reported off-leash frequency and perception of risk for gastrointestinal
      parasitism are not associated in owners of urban park-attending dogs: A
      multifactorial investigation.
AB  - Associations between park use and infections with gastrointestinal (GI) parasites
      in dogs (Canis familiaris) have been previously observed, suggesting park use may
      pose risks for infection in dogs, and potentially, in humans. This study was
      conducted to establish the overall level of perceived risk of parasitism in dogs,
      the frequency of unleashing dogs in parks, and to determine if dog owners' risk
      perceptions of parasite transmission among humans and dogs are associated with
      the reported frequency of unleashing dogs. From June to September 2010, 635
      surveys were administered to dog owners in nine city parks in Calgary, Alberta,
      by the lead author to explore dog-walking behaviors in parks under differing
      leashing regulations. From these, a subset of 316 questionnaires were analyzed to
      examine associations between behavioral and dog demographic factors, risk
      perception and acceptability of perceived risks of dog and human parasitism, and
      education regarding parasitism in dogs and humans. Multivariate statistics were
      conducted using three separate Chi-Square Automatic Interaction Detection (CHAID)
      decision trees to model risk perception of dogs becoming parasitized while in the
      park, risk perception of zoonotic transmission, and off-leash frequency.
      Predictors included recreational behaviors, dog demographics, risk perception of
      park-based and zoonotic transmission, education regarding parasites, and leashing
      regulations (e.g. on-leash, off-leash, or mixed management parks). The perceived
      risk of park-based transmission was relatively higher than perception of zoonotic
      transmission and the majority of people unleashed their dogs at least some of the
      time. Risk perception was not associated with off-leash frequency in dogs and
      risk perception and off-leash frequency were associated with factors other than
      each other. The results suggest owners may underestimate the potential risks for
      parasitism related to some dog-walking behaviours, and are relevant for public
      and animal health. 

PMID- 25979856
TI  - An experimental study on amelioration of dyslipidemia-induced atherosclesis by
      Clematichinenoside through regulating Peroxisome proliferator-activated receptor
      alpha mediated apolipoprotein A-I, A-II and C-III.
AB  - Prevention or amelioration the prevalence of atherosclerosis has been an
      effective strategy in the management of cardiovascular diseases. The aim of the
      study was to scrutinize the effect of Clematichinenoside (AR) on dyslipidemia
      induced atherosclerosis and explore its capability on expression of Peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha), apolipoprotein A-I (APOA1)
      and A-II (APOA2), and suppression of apolipoprotein C-III (APOC3) genes and
      proteins. In the present study, we investigated atherosclerosis effect of AR
      using a combination of high-fat diet and balloon injury model in rabbits. The
      levels of biochemical indicators were evaluated in plasma, liver and HepG2 cells
      using immunoassay technology. In order to expose the underlying mechanism, we
      evaluated the regulation of PPAR-alpha, APOA1, APOA2 and APOC3 expressions by AR,
      and we further evaluated the interactions between them after transfection with
      shRNA (shPPAR-alpha) and, the action of PPAR-alpha in HepG2 cells. We could find
      that AR markedly promoted the PPAR-alpha transfer from cytoplasm to nucleus which
      resulted in the alteration of APOA1, APOA2 and APOC3 expressions in HepG2 cells.
      Moreover, AR significantly reduced total cholesterol, triglycerides and low
      density lipoprotein cholesterol (LDL-C) levels, and elevated high-density
      lipoprotein cholesterol (HDL-C) level, which play an important role in
      dyslipidemia-induced atherosclerosis. In conclusion, AR ameliorated
      atherosclerosis via the regulation of hepatic lipid metabolism, and AR also
      contributed to the activation of PPAR-alpha, APOA1, APOA2 and APOC3. Therefore,
      AR could be a potential therapeutic agent in the treatment of atherosclerosis. 

PMID- 25979857
TI  - Cardiovascular and renal effect of CNAAC: An innovatively designed natriuretic
      peptide.
AB  - Natriuretic peptides (NPs) have natriuretic, diuretic and vasodilator effects. An
      innovative natriuretic peptide analogue called CNAAC (a new chimera peptide
      combining the C-terminus and ring of ANP with the N-terminus of CNP) was designed
      to determine whether it has any cardiovascular and renal effect. Abdominal aorta
      of rats were isolated and vascular ring perfusion was employed to compare the
      vasodilator effect and cGMP excretion effect of CNAAC with natural NPs. Urine
      volume and urine cGMP levels after intravenous injection of CNAAC and natural NPs
      were determined. Hemodynamic methods were employed to assess the effect of CNAAC
      and natural NPs on MAP. CNAAC relaxed abdominal aorta in a dose-dependent manner
      and was independent of endothelium. The vasodilating effect of CNAAC was
      significantly attenuated in the presence of NPR-A antibody, GC inhibitor, and
      KATP inhibitor and was abolished by PKG inhibitor. Abdominal aortic cGMP
      production increased after incubation with NPs. Urine volume, plasma cGMP, and
      urine cGMP increased and MAP decreased dramatically after intravenous injection
      of CNAAC. CNAAC has a potent vasodilating effect, probably by activating K(+)
      channels via NPR-A/sGC/cGMP pathway. Exogenous administration of CNAAC elicits
      diuretic and hypotensive effects. 

PMID- 25979859
TI  - IVC filter perforation through the duodenum found after years of abdominal pain.
AB  - BACKGROUND: The number of IVC filter-related complications has increased with
      their growing utilization; however, IVC filter perforation of the duodenum is
      rare. It can manifest with nonspecific abdominal pain, gastrointestinal bleeding,
      cava-duodenal fistula, or small bowel obstruction. CASE REPORT: A 67-year-old
      female presented with several years of right upper quadrant abdominal pain which
      was exacerbated by movement and food intake. She had a history of hepatic
      steatosis, cholecystectomy, and multiple DVTs with inferior vena cava filter
      placement. Physical exam was unremarkable. Laboratory tests demonstrated elevated
      alkaline phosphatase and transaminases. Esophagogastroduodenoscopy revealed a
      thin metallic foreign body embedded in the duodenal wall and protruding into the
      duodenal lumen with surrounding erythema and edema, but no active hemorrhage.
      Further evaluation with non-contrast CT scan revealed that one of the prongs of
      her IVC filter had perforated through the vena cava wall into the adjacent
      duodenum. Exploratory laparotomy was required for removal of the IVC filter and
      repair of the vena cava and duodenum. Her post-operative course was uneventful.
      CONCLUSIONS: In patients with history of IVC filter placement with non-specific
      abdominal pain, a high clinical suspicion of IVC filter perforation of the
      duodenum should be raised, as diagnosis may be challenging. CT scan and EGD are
      valuable in the diagnosis. Excellent outcomes have been reported with open
      surgical filter removal. Low retrieval rates of IVC filters have led to increased
      complications; hence, early removal should be undertaken as clinically indicated.

PMID- 25979858
TI  - The protective effects of endogenous hydrogen sulfide modulator, S-propargyl
      cysteine, on high glucose-induced apoptosis in cardiomyocytes: A novel mechanism
      mediated by the activation of Nrf2.
AB  - S-propargyl-cysteine (SPRC) is a novel synthetic molecule exerting antioxidant
      effects via elevating generation of endogenous H2S. Our study aimed to elucidate
      possible antioxidant mechanisms of SPRC in hyperglycemia-induced oxidative
      stress. H9C2 cells were treated with SPRC or NaHS at the indicated concentration
      before being treated with high glucose for 48h. Follow-up experiments were based
      on detailed description given in Section 2. SD rats were injected with
      Streptozocin (STZ) to induce diabetes as previously reported. Diabetic rats were
      administrated with SPRC, NaHS or solution respectively for one week before the
      rats were killed for follow-up experiments. Our work found that SPRC remarkably
      attenuated high glucose induced generation of reactive oxygen species and
      apoptosis in H9C2 cells. SPRC increased stability and nuclear translocation of
      Nuclear factor erythroid 2-related factor 2 (Nrf2), up-regulated expression of
      antioxidant enzyme superoxide dismutase (SOD) and interfered with the interaction
      between Kelch-like ECH-associated protein 1 (KEAP1) and Nrf2. SPRC activated Nrf2
      via Cystathionase-gamma-lyase (CSE) and Akt pathway. CSE inhibitor PAG and Akt
      inhibitor LY294002 could reverse the protective effects of SPRC. Knockdown of
      Nrf2 by shRNA also blocked SPRC up-regulated expression of CSE. Similar results
      of protein expression and hypoglycemic activity of SPRC were observed in STZ
      induced diabetic rats. 

PMID- 25979860
TI  - Altered cortical processing of observed pain in patients with fibromyalgia
      syndrome.
AB  - Fibromyalgia syndrome (FMS) is characterized by widespread chronic pain, fatigue,
      sleep disorders, and cognitive-emotional disturbance. Patients with FMS exhibit
      increased sensitivity to experimental pain and pain-related cues, as well as
      deficits in emotional regulation. The present study investigated the
      spatiotemporal patterns of brain activations for observed pain in 19 patients
      with FMS and 18 age-matched, healthy control individuals using event-related
      potential analysis. Patients with FMS attributed greater pain and unpleasantness
      to pain pictures, relative to healthy control participants. An augmented late
      positive potential (LPP) component (>500 milliseconds) was found in patients
      viewing both pain and nonpain pictures, and this amplitude difference in the LPP
      covaried with perceived unpleasantness of pictures. Mid-latency potentials (250
      450 milliseconds) demonstrated similar amplitude increases of positive potentials
      in the FMS patient group. By contrast, the short-latency positive potential (140
      milliseconds) was reduced in patients with FMS relative to healthy control
      participants. Results suggest amplitude increases to mid- to long-latency
      cortical activations in patients with FMS, which are known to reflect emotional
      control and motivational salience of stimuli. PERSPECTIVE: Patients with FMS
      demonstrate increased activations associated with pain and nonpain pictures. The
      findings suggest that even innocuous, everyday visual stimuli with somatic
      connotations may challenge the emotional state of patients with FMS. Our study
      points toward the importance of cognitive-emotional therapeutic approaches for
      the treatment of FMS.

PMID- 25979861
TI  - Transplantation of Induced Pluripotent Stem Cell-Derived Neural Stem Cells
      Mediate Functional Recovery Following Thoracic Spinal Cord Injury Through
      Remyelination of Axons.
AB  - : Neural stem cells (NSCs) from embryonic or fetal/adult tissue sources have
      shown considerable promise in regenerative strategies for traumatic spinal cord
      injury (SCI). However, there are limitations with their use related to the
      availability, immunogenicity, and uncertainty of the mechanisms involved. To
      address these issues, definitive NSCs derived from induced pluripotent stem (iPS)
      cells generated using a nonviral, piggyBac transposon approach, were
      investigated. Committed NSCs were generated from iPS cells using a free-floating
      neurosphere methodology previously described by our laboratory. To delineate the
      mechanism of action, specifically the role of exogenous myelination, NSCs derived
      from wildtype (wt) and nonmyelinating Shiverer (shi) iPS cell lines were used
      following thoracic SCI with subacute intraspinal transplantation. Behavioral,
      histological, and electrophysiological outcomes were analyzed to assess the
      effectiveness of this treatment. The wt- and shi-iPS-NSCs were validated and
      shown to be equivalent except in myelination capacity. Both iPS-NSC lines
      successfully integrated into the injured spinal cord and predominantly
      differentiated to oligodendrocytes, but only the wt-iPS-NSC treatment resulted in
      a functional benefit. The wt-iPS-dNSCs, which exhibited the capacity for
      remyelination, significantly improved neurobehavioral function (Basso Mouse Scale
      and CatWalk), histological outcomes, and electrophysiological measures of axonal
      function (sucrose gap analysis) compared with the nonmyelinating iPS-dNSCs and
      cell-free controls. In summary, we demonstrated that iPS cells can generate
      translationally relevant NSCs for applications in SCI. Although NSCs have a
      diverse range of functions in the injured spinal cord, remyelination is the
      predominant mechanism of recovery following thoracic SCI. SIGNIFICANCE: Gain-of
      function/loss-of-function techniques were used to examine the mechanistic
      importance of graft-derived remyelination following thoracic spinal cord injury
      (SCI). The novel findings of this study include the first use of neural stem
      cells (NSCs) from induced pluripotent stem cells (iPSCs) derived using the clonal
      neurosphere expansion conditions, for the treatment of SCI, the first
      characterization and in vivo application of iPSCs from Shiverer mouse
      fibroblasts, and the first evidence of the importance of remyelination by
      pluripotent-sourced NSCs for SCI repair and regeneration.

PMID- 25979862
TI  - Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.
AB  - : Mesenchymal stem cells (MSCs) have captured the attention and research
      endeavors of the scientific world because of their differentiation potential.
      However, there is accumulating evidence suggesting that the beneficial effects of
      MSCs are predominantly due to the multitude of bioactive mediators secreted by
      these cells. Because the paracrine potential of MSCs is closely related to their
      microenvironment, the present study investigated and characterized select aspects
      of the human MSC (hMSC) secretome and assessed its in vitro and in vivo
      bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2)
      and hypoxia (5% O2), conditions that reflect the environment to which MSCs are
      exposed during MSC-based therapies in vivo. In contrast to supernatant
      conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM
      from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced
      chemotactic and proangiogenic properties and a significant (p < .05) decrease in
      the inflammatory mediator content. An analysis of the hMSC secretome revealed a
      specific profile under near anoxia: hMSCs increase their paracrine expression of
      the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C,
      interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly
      decrease expression of several inflammatory/immunomodulatory mediators. These
      findings provide new evidence that elucidates aspects of great importance for the
      use of MSCs in regenerative medicine and could contribute to improving the
      efficacy of such therapies. SIGNIFICANCE: The present study investigated and
      characterized select aspects of the human mesenchymal stem cell (hMSC) secretome
      and assessed its in vitro and in vivo biological bioactivity as a function of
      oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2),
      conditions that reflect the environment to which MSCs are exposed during MSC
      based therapies in vivo. The present study provided the first evidence of a shift
      of the hMSC cytokine signature induced by oxygen tension, particularly near
      anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near
      anoxia exhibited significantly enhanced chemotactic and proangiogenic properties
      and a significant decrease in the inflammatory mediator content. These findings
      provide new evidence that elucidates aspects of great importance for the use of
      MSCs in regenerative medicine, could contribute to improving the efficacy of such
      therapies, and most importantly highlighted the interest in using conditioned
      media in therapeutic modalities.

PMID- 25979863
TI  - Robust Expansion of Human Pluripotent Stem Cells: Integration of Bioprocess
      Design With Transcriptomic and Metabolomic Characterization.
AB  - : Human embryonic stem cells (hESCs) have an enormous potential as a source for
      cell replacement therapies, tissue engineering, and in vitro toxicology
      applications. The lack of standardized and robust bioprocesses for hESC expansion
      has hindered the application of hESCs and their derivatives in clinical settings.
      We developed a robust and well-characterized bioprocess for hESC expansion under
      fully defined conditions and explored the potential of transcriptomic and
      metabolomic tools for a more comprehensive assessment of culture system impact on
      cell proliferation, metabolism, and phenotype. Two different hESC lines (feeder
      dependent and feeder-free lines) were efficiently expanded on xeno-free
      microcarriers in stirred culture systems. Both hESC lines maintained the
      expression of stemness markers such as Oct-4, Nanog, SSEA-4, and TRA1-60 and the
      ability to spontaneously differentiate into the three germ layers. Whole-genome
      transcriptome profiling revealed a phenotypic convergence between both hESC lines
      along the expansion process in stirred-tank bioreactor cultures, providing strong
      evidence of the robustness of the cultivation process to homogenize cellular
      phenotype. Under low-oxygen tension, results showed metabolic rearrangement with
      upregulation of the glycolytic machinery favoring an anaerobic glycolysis Warburg
      effect-like phenotype, with no evidence of hypoxic stress response, in contrast
      to two-dimensional culture. Overall, we report a standardized expansion
      bioprocess that can guarantee maximal product quality. Furthermore, the "omics"
      tools used provided relevant findings on the physiological and metabolic changes
      during hESC expansion in environmentally controlled stirred-tank bioreactors,
      which can contribute to improved scale-up production systems. SIGNIFICANCE: The
      clinical application of human pluripotent stem cells (hPSCs) has been hindered by
      the lack of robust protocols able to sustain production of high cell numbers, as
      required for regenerative medicine. In this study, a strategy was developed for
      the expansion of human embryonic stem cells in well-defined culture conditions
      using microcarrier technology and stirred-tank bioreactors. The use of
      transcriptomic and metabolic tools allowed detailed characterization of the cell
      based product and showed a phenotypic convergence between both hESC lines along
      the expansion process. This study provided valuable insights into the metabolic
      hallmarks of hPSC expansion and new information to guide bioprocess design and
      media optimization for the production of cells with higher quantity and improved
      quality, which are requisite for translation to the clinic.

PMID- 25979864
TI  - Effects of acupuncture at ST25 on inflammatory mediators and nuclear factor
      kappaB activation in a rat model of severe acute pancreatitis.
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) and manual
      acupuncture (MA) at ST25 on inflammatory mediators and nuclear factor kappa-B (NF
      kappaB) activation in rats with sodium taurocholate-induced severe acute
      pancreatitis (SAP). METHODS: Eighty-eight male Sprague-Dawley rats were randomly
      divided into four groups: control (sham-operated), SAP, SAP+EA and SAP+MA (n=22
      each). A SAP model was established by injecting 3.5% sodium taurocholate 1 mL/kg
      into the pancreatic duct. In each group, animals were killed at t=3 h (n=7), 6 h
      (n=7) and 12 h (n=8) after the procedure. Pancreatic expression of NF-kappaB was
      examined by immunohistochemical staining. The levels of tumour necrosis factor
      alpha (TNF-alpha) and interleukin 6 (IL-6) in serum were determined by ELISA.
      Pathological changes in the pancreas were examined microscopically. RESULTS:
      Serum levels of TNF-alpha and IL-6 increased and morphological changes consistent
      with tissue damage were observed in the pancreas of SAP rats. NF-kappaB p65
      expression was significantly higher in the SAP group than in the sham-operated
      group (p<0.05). Treatment with acupuncture at ST25 attenuated morphological
      damage and reduced levels of TNF-alpha and IL-6 in serum. NF-kappaB p65
      expression was also significantly reduced by acupuncture at ST25 in the pancreas
      at 6 and 12 h after the procedure (p<0.05). There were no significant differences
      between the SAP+EA and SAP+MA groups. CONCLUSIONS: Acupuncture at ST25 might have
      a therapeutic effect on rats with SAP through inhibition of NF-kappaB expression
      and a reduction in the release of pro-inflammatory cytokines.

PMID- 25979865
TI  - Electroacupuncture attenuates collagen-induced arthritis in rats through
      vasoactive intestinal peptide signalling-dependent re-establishment of the
      regulatory T cell/T-helper 17 cell balance.
AB  - OBJECTIVE: Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg)
      cells is causally linked to the development of rheumatoid arthritis (RA). In this
      study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic
      benefits in RA through activation of vasoactive intestinal peptide (VIP)
      dependent signalling and restoration of the Th17/Treg cell balance. MATERIALS AND
      METHODS: A collagen-induced arthritis (CIA) model was induced in Sprague-Dawley
      rats by injection of bovine type II collagen in incomplete Freund's adjuvant on
      day 0 and day 7. Three days after the second injection, EA was given at
      acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP
      signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was
      administered intraperitoneally 30 min before EA. Inflammatory and pathological
      responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg
      and Th17 cell frequencies in the spleen were determined. RESULTS: EA
      significantly reduced the severity of CIA, as evidenced by reduced paw volumes,
      arthritis scores and inflammation scores. EA significantly increased mRNA
      expression of the VIP receptor VPAC1 and led to an elevation in CD4(+)FOXP3(+)
      Treg cell frequency and a reduction in CD4(+)IL17(+) Th17 cell frequency. Pre
      injection of a VIP receptor antagonist significantly reversed EA-induced
      expansion of Treg cells, but did not alter the frequencies of Th17 cells.
      CONCLUSIONS: EA exerts anti-inflammatory effects in a collagen-induced rat model
      of arthritis. These effects appear to be mediated through activation of VIP
      signalling and re-establishment of the Th17/Treg cell balance.

PMID- 25979866
TI  - Do solar cycles influence giant cell arteritis and rheumatoid arthritis
      incidence?
AB  - OBJECTIVE: To examine the influence of solar cycle and geomagnetic effects on the
      incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). METHODS:
      We used data from patients with GCA (1950-2004) and RA (1955-2007) obtained from
      population-based cohorts. Yearly trends in age-adjusted and sex-adjusted
      incidence were correlated with the F10.7 index (solar radiation at 10.7 cm
      wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a
      proxy for the westward auroral electrojet and a measure of geomagnetic activity).
      Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates.
      RESULTS: The correlation of GCA incidence with AL is highly significant: GCA
      incidence peaks 0-1 year after the AL reaches its minimum (ie, auroral electrojet
      reaches a maximum). The correlation of RA incidence with AL is also highly
      significant. RA incidence rates are lowest 5-7 years after AL reaches maximum.
      AL, GCA and RA incidence power spectra are similar: they have a main peak
      (periodicity) at about 10 years and a minor peak at 4-5 years. However, the RA
      incidence power spectrum main peak is broader (8-11 years), which partly explains
      the lower correlation between RA onset and AL. The auroral electrojets may be
      linked to the decline of RA incidence more strongly than the onset of RA. The
      incidences of RA and GCA are aligned in geomagnetic latitude. CONCLUSIONS: AL and
      the incidences of GCA and RA all have a major periodicity of about 10 years and a
      secondary periodicity at 4-5 years. Geomagnetic activity may explain the temporal
      and spatial variations, including east-west skewness in geographic coordinates,
      in GCA and RA incidence, although the mechanism is unknown. The link with solar,
      geospace and atmospheric parameters need to be investigated. These novel findings
      warrant examination in other populations and with other autoimmune diseases.

PMID- 25979867
TI  - Intravenous thrombolysis guided by a telemedicine consultation system for acute
      ischaemic stroke patients in China: the protocol of a multicentre historically
      controlled study.
AB  - INTRODUCTION: The rate of intravenous thrombolysis with tissue-type plasminogen
      activator or urokinase for stroke patients is extremely low in China. It has been
      demonstrated that a telestroke service may help to increase the rate of
      intravenous thrombolysis and improve stroke care quality in local hospitals. The
      aim of this study, also called the Acute Stroke Advancing Program, is to evaluate
      the effectiveness and safety of decision-making concerning intravenous
      thrombolysis via a telemedicine consultation system for acute ischaemic stroke
      patients in China. METHODS AND ANALYSIS: This is a multicentre historically
      controlled study with a planned enrolment of 300 participants in each of two
      groups. The telestroke network consists of one hub hospital and 14 spoke
      hospitals in underserved regions of China. The usual stroke care quality in the
      spoke hospitals without guidance from the hub hospital will be used as the
      historical control. The telemedicine consultation system is an interactive, two
      way, wireless, audiovisual system accessed on portable devices. The primary
      outcome is the percentage of patients treated with intravenous thrombolysis
      within 4.5 h of stroke onset. ETHICS AND DISSEMINATION: The project has been
      approved by the Institutional Review Board of Xijing Hospital. The results will
      be published in scientific journals and presented to local government and
      relevant institutes. TRIAL REGISTRATION NUMBER: NCT02088346 (12 March 2014).

PMID- 25979868
TI  - High-intensity statin therapy in patients with chronic kidney disease: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of high-intensity statin therapy
      in patients with chronic kidney disease (CKD). DESIGN: A systematic review and
      meta-analysis. DATA SOURCES: Randomised controlled trials (RCTs) comparing high
      intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20/40 mg) with
      moderate/mild statin treatment or placebo were derived from the databases
      (PubMed, Embase, Ovid, the Cochrane Central Register of Controlled Trials
      (CENTRAL) in the Cochrane Library, and ISI Web of Knowledge). OUTCOME MEASURE:
      Primary end points: clinical events (all-cause mortality, stroke, myocardial
      infarction and heart failure); secondary end points: serum lipid, renal function
      changes and adverse events. RESULTS: A total of six RCTs with 10,993 adult
      patients with CKD were included. A significant decrease in stroke was observed in
      the high-intensity statin therapy group (RR 0.69, 95% CI 0.56 to 0.85). However,
      the roles of high-intensity statin in decreasing all-cause mortality (RR 0.85,
      95% CI 0.67 to 1.09), myocardial infarction (RR 0.69, 95% CI 0.40 to 1.18) and
      heart failure (RR 0.73, 95% CI 0.48 to 1.13) remain unclear with low evidence.
      High-intensity statin also had obvious effects on lowering the LDL-C level but no
      clear effects on renal protection. Although pooled results showed no significant
      difference between the intervention and control groups in adverse event
      occurrences, it was still insufficient to put off the doubts that high-intensity
      statin might increase adverse events because of limited data sources and low
      quality evidences. CONCLUSIONS: High-intensity statin therapy could effectively
      reduce the risk of stroke in patients with CKD. However, its effects on all-cause
      mortality, myocardial infarction, heart failure and renal protection remain
      unclear. Moreover, it is hard to draw conclusions on the safety assessment of
      intensive statin treatment in this particular population. More studies are needed
      to credibly evaluate the effects of high-intensity statin therapy in patients
      with CKD.

PMID- 25979869
TI  - Intrauterine insemination: a UK survey on the adherence to NICE clinical
      guidelines by fertility clinics.
AB  - OBJECTIVE: To evaluate the awareness and response of fertility clinics in the UK
      to the National Institute for Health and Care Excellence (NICE) guideline
      recommendation that intrauterine insemination (IUI) should not be offered
      routinely, in order to report on current practice in the UK. DESIGN: Online
      questionnaire survey of fertility clinics in the UK regarding their current
      clinical practice of IUI, formal discussion of the guideline recommendations, and
      any alterations made since the recommendations. SETTING: 66 UK fertility clinics
      licensed to provide IUI. PARTICIPANTS: 46 fertility clinics, including 6 clinic
      groups which represent 70% of all clinics and clinic groups licensed to provide
      IUI in April 2014 when the survey email was sent. RESULTS: Of the 46 clinics that
      responded, 96% (44/46) of clinics continue to offer IUI. 98% (43/44) of those
      offering IUI also use ovarian stimulation. The most commonly used medications for
      ovarian stimulation are gonadotrophins (95%), followed by clomiphene citrate
      (49%) and letrozole (19%). 78% (36/46) of clinics had formally discussed NICE
      guideline recommendations. 17 clinics (37%) had made some changes to their
      practices; as a result, four clinics reported a reduction in the number of IUI
      cycles, six clinics had restricted the indications for IUI, and five clinics had
      begun informing patients of the guideline recommendations, while two did not
      specify. CONCLUSIONS: The majority of clinics were aware of the guideline
      recommendations. However, only a small proportion of clinics had made significant
      changes to their practice by reducing the number of IUI cycles or restricting the
      clinical indications for IUI. The availability of further evidence will assist
      NICE and clinicians in making recommendations on the use of IUI. There is a need
      to further explore the reasons for the lack of adherence to the recommendations.

PMID- 25979870
TI  - Fructosamine measurement for diabetes mellitus diagnosis and monitoring: a
      systematic review and meta-analysis protocol.
AB  - INTRODUCTION: Fructosamine is a marker of glucose control reflecting the average
      glycaemic level over the preceding 2-3 weeks. Fructosamine has not gained as much
      popularity as glycated haemoglobin (HbA1c) for diabetes mellitus (DM) control
      monitoring, and the related underlying reasons remain unclear. We aim to search
      for and summarise available evidence on the accuracy of fructosamine measurements
      to diagnose and monitor DM. METHODS AND ANALYSIS: This systematic review will
      include randomised control trials, controlled before-and-after studies, time
      series designs, cohort studies, case-control studies and cross-sectional surveys
      reporting the diagnosis and/or monitoring of DM (type 1 DM, type 2 DM and
      gestational DM) with fructosamine compared with other measures of glycaemia
      (fasting glucose, oral glucose tolerance test, random glucose, HbA1c), without
      any language restriction. We will perform electronic searches in PubMed, Scopus
      and other databases, supplemented with manual searches. Articles published from 1
      January 1980 to 30 June 2015 will be eligible for inclusion in this review. Two
      authors will independently screen, select studies, extract data and assess the
      risk of bias with discrepancies resolved by consensus. We will assess clinical
      heterogeneity by examining the types of interventions and outcomes in each study,
      and pool studies judged to be clinically homogeneous. We will also assess
      statistical heterogeneity using the chi(2) test of homogeneity and quantify it
      using the I(2) statistic. Absolute accuracy measures (sensitivity, specificity)
      will be pooled in a bivariate random-effects model, allowing for intersetting
      variability. Negative and positive predictive values will be computed for
      fructosamine, compared with another measure of glycaemia from the pooled
      estimates of sensitivity and specificity, using Bayes' theorem. ETHICS AND
      DISSEMINATION: This systematic review will use data from published studies and
      does not require ethics approval. Findings will be published in a peer-reviewed
      journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER:
      PROSPERO (ID=CRD42015015930).

PMID- 25979871
TI  - Does smoking reduction worsen mental health? A comparison of two observational
      approaches.
AB  - OBJECTIVES: The association between smoking reduction and mental health is of
      particular interest given that many smokers report that smoking offers mental
      health benefits. We aimed to assess the association between smoking reduction and
      change in mental health using two different analytical approaches to determine if
      there was any evidence of an association. There were no prior hypotheses. DESIGN:
      A secondary analysis of prospective individual level patient data from 5 merged
      placebo-controlled randomised trials of nicotine replacement therapy for smoking
      reduction. PARTICIPANTS: All participants were adult smokers, selected because
      they wanted to reduce but not stop smoking, and had smoked for at least 3 years.
      Participants were excluded if they were pregnant, breastfeeding, under
      psychiatric care, deemed to be unfit by a general practitioner, or part of a
      cessation programme. 2066 participants were enrolled in the trials, 177
      participants were biologically validated as prolonged reducers, and 509 as
      continuing smokers at both 6-week and 18-week follow-ups. PRIMARY OUTCOME: Change
      in mental health from baseline to an 18-week follow-up was measured using the
      emotional well-being subscale on the Short Form Health Survey-36. RESULTS: After
      adjustment for confounding variables, the differences for reducers compared with
      continuing smokers were: regression modelling -0.6 (95% CI -4.4 to 3.2) and
      propensity score matching 1.1 (95% CI -2.0 to 4.1). CONCLUSIONS: Smoking
      reduction, sustained for at least 12 weeks, was not associated with change in
      mental health, suggesting that reducing smoking was no better or worse for mental
      health than continuing smoking. Clinicians offering smoking reduction as a route
      to quit can be confident that, on average, smoking reduction is not associated
      with negative change in mental health.

PMID- 25979872
TI  - Barriers to Help Seeking for Lesbian, Gay, Bisexual, Transgender, and Queer
      Survivors of Intimate Partner Violence.
AB  - Intimate partner violence (IPV) is a pervasive and devastating social problem
      that is estimated to occur in one of every four opposite-sex relationships and at
      least one of every five same-sex romantic relationships. These estimates may not
      represent violence against those who identify as transgender or genderqueer, and
      very little comprehensive research has been conducted on IPV within these
      populations. One statewide study on IPV found rates of IPV were as high as one of
      every two transgender individuals. In order to cope with the effects of abuse or
      leave an abusive partner, many lesbian, gay, bisexual, transgender, and
      genderqueer (LGBTQ) IPV survivors seek support from others. However, LGBTQ IPV
      survivors may experience unique difficulties related to their sexual orientation
      and gender identity when seeking assistance. This article reviews the literature
      on LGBTQ IPV and suggests three major barriers to help-seeking exist for LGBTQ
      IPV survivors: a limited understanding of the problem of LGBTQ IPV, stigma, and
      systemic inequities. The significance and consequences of each barrier are
      discussed, and suggestions for future research, policy, and practice are
      provided.

PMID- 25979874
TI  - Incidentally detected large neonatal ductus arteriosus aneurysm.

PMID- 25979873
TI  - Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal
      Cells.
AB  - Malignant cells drive the generation of a desmoplastic and immunosuppressive
      tumor microenvironment. Cancer-associated stromal cells (CASC) are a
      heterogeneous population that provides both negative and positive signals for
      tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker
      of a major subset of CASCs in virtually all carcinomas. Clinically, FAP
      expression serves as an independent negative prognostic factor for multiple types
      of human malignancies. Prior studies established that depletion of FAP(+) cells
      inhibits tumor growth by augmenting antitumor immunity. However, the potential
      for immune-independent effects on tumor growth have not been defined. Herein, we
      demonstrate that FAP(+) CASCs are required for maintenance of the provisional
      tumor stroma because depletion of these cells, by adoptive transfer of FAP
      targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix
      proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also
      decreased tumor vascular density and restrained growth of desmoplastic human lung
      cancer xenografts and syngeneic murine pancreatic cancers in an immune
      independent fashion. Adoptive transfer of FAP-CAR T cells also restrained
      autochthonous pancreatic cancer growth. These data distinguish the function of
      FAP(+) CASCs from other CASC subsets and provide support for further development
      of FAP(+) stromal cell-targeted therapies for the treatment of solid tumors.

PMID- 25979875
TI  - Consumer empowerment and the essential care environment ingredients.

PMID- 25979876
TI  - American Psychiatric Nurses Association (APNA) revision of its Position Statement
      on the Use of Seclusion and Restraint.

PMID- 25979877
TI  - Positive influence of telephone support by health professionals in promoting
      health interventions.

PMID- 25979878
TI  - Author's Reply.

PMID- 25979879
TI  - Binge eating among racial minority groups in the United States: an integrative
      review.
AB  - BACKGROUND: Binge eating (BE) is a disordered eating behavior that has been
      linked to the development of eating disorders and obesity, with the latter being
      a condition with higher prevalence rates among some racial minority groups.
      Although researchers have begun to examine characteristics of BE among racial
      minority groups, it is unclear how these differ from White populations.
      OBJECTIVE: This article provides an integrative review of published literature
      within the past decade reporting on the characteristics of BE in minority
      compared with White racial groups. METHOD: Health care computerized databases
      were searched using key terms. RESULTS: Eighteen research studies met the
      inclusion criteria. More than half of the studies reviewed reported racial
      differences in some aspect of BE; however, heterogeneity in the definition and
      measurement of BE limits the ability to compare findings across studies.
      CONCLUSIONS: BE is reported across racial groups. To determine whether meaningful
      differences in BE exist by race, further studies using the same conceptual and
      operational definitions of BE are needed.

PMID- 25979880
TI  - The influence of teaching method on performance of suicide assessment in
      baccalaureate nursing students.
AB  - BACKGROUND: Student nurses identify many barriers to assessing patients' risk for
      suicide. OBJECTIVE: This pilot study developed and tested an innovative active
      learning strategy using simulated standardized patients to determine its
      effectiveness in teaching suicide assessment skills to a sample of 34 junior and
      senior baccalaureate nursing students. DESIGN: This study employed an
      experimental, two-group posttest design and three National League for
      Nursing/Laerdal Simulation Evaluation instruments. After reading about suicide
      assessment, the experimental group was exposed to a simulated standardized
      patient portraying a suicidal patient. The control group received a recorded
      lecture on suicide assessment. RESULTS: The experimental group demonstrated a
      significant difference in student scores of self-confidence, satisfaction, and
      student perceptions of the educational practices (active learning, collaboration,
      and appeal to diverse learning styles) when compared to the lecture format.
      CONCLUSION: Suicide assessment is a critical assessment skill set that can be
      effectively taught to nursing students using standardized patients.

PMID- 25979881
TI  - Development and testing of the combined assessment of psychiatric environments: a
      patient-centered quality measure for inpatient psychiatric treatment.
AB  - BACKGROUND: Inpatient psychiatric treatment satisfaction measures are not
      constructed from patients' perspective of hospitalization experiences that they
      deem meaningful and important. OBJECTIVE: To develop and conduct psychometric
      testing of a measure that evaluates person-centered care on inpatient psychiatric
      units, the Combined Assessment of Psychiatric Environments (CAPE). The measure is
      built on a theoretical framework holding that if optimal care is to be achieved,
      all major stakeholders (patients and staff) need to experience a positive
      environment. DESIGN: An instrument development design was used to create the
      patient/staff nurse versions of the CAPE and to test their dimensions. The pilot
      versions of the CAPE were tested on six inpatient psychiatric units to determine
      the psychometrics of the staff/patient versions. RESULTS: The overall reliability
      of both versions of the CAPE (staff/patient) was .91. The test-retest reliability
      for both versions was significant at the .01 level. Construct validity was
      established via factor analysis. Criterion-related validity was demonstrated by
      correlations of the two versions of the CAPE to instruments that were
      conceptually related. CONCLUSION: The CAPE is a valid and reliable instrument
      that can be used to examine practice and the patient experience on inpatient
      psychiatric units. The CAPE highlights that patient-centered environments of care
      are intertwined with staff experiences of support for their role.

PMID- 25979882
TI  - A Clinical Translation of the Article Titled "Development and Testing of the
      Combined Assessment of Psychiatric Environments (CAPE): A Patient-Centered
      Quality Measure for Inpatient Psychiatric Treatment".
AB  - BACKGROUND: There is a need for an easy-to-use measure of meaningful and
      important inpatient psychiatric treatment. METHOD: This is a clinical translation
      of a research article by Delaney and colleagues (this issue of JAPNA) that
      describes the development and testing of a new measure called the Combined
      Assessment of Psychiatric Environments (CAPE). The measure was tested with
      patients and staff on six different inpatient psychiatric units. RESULTS: The
      staff and patient versions of the CAPE were shown to be valid (accurate measure
      of safe, patient-centered care) and reliable (precise measure that shows
      stability over time). CONCLUSION: The CAPE is a new measure that can be used to
      examine staff and patient experiences of nursing practice on inpatient
      psychiatric units.

PMID- 25979883
TI  - Reaerosolization of Spores from Flooring Surfaces To Assess the Risk of
      Dissemination and Transmission of Infections.
AB  - The aim of this study was to quantify reaerosolization of microorganisms caused
      by walking on contaminated flooring to assess the risk to individuals accessing
      areas contaminated with pathogenic organisms, for example, spores of Bacillus
      anthracis. Industrial carpet and polyvinyl chloride (PVC) floor coverings were
      contaminated with aerosolized spores of Bacillus atrophaeus by using an artist
      airbrush to produce deposition of ~10(3) to 10(4) CFU . cm(-2). Microbiological
      air samplers were used to quantify the particle size distribution of the aerosol
      generated when a person walked over the floorings in an environmental chamber.
      Results were expressed as reaerosolization factors (percent per square centimeter
      per liter), to represent the ratio of air concentration to surface concentration
      generated. Walking on carpet generated a statistically significantly higher
      reaerosolization factor value than did walking on PVC (t = 20.42; P < 0.001).
      Heavier walking produced a statistically significantly higher reaerosolization
      factor value than did lighter walking (t = 12.421; P < 0.001). Height also had a
      statistically significant effect on the reaerosolization factor, with higher
      rates of recovery of B. atrophaeus at lower levels, demonstrating a height
      dependent gradient of particle reaerosolization. Particles in the respirable size
      range were recovered in all sampling scenarios (mass mean diameters ranged from
      2.6 to 4.1 MUm). The results of this study can be used to produce a risk
      assessment of the potential aerosol exposure of a person accessing areas with
      contaminated flooring in order to inform the choice of appropriate respiratory
      protective equipment and may aid in the selection of the most suitable flooring
      types for use in health care environments, to reduce aerosol transmission in the
      event of contamination. 

PMID- 25979884
TI  - Wastewater Analysis Indicates that Genetically Diverse Astroviruses, Including
      Strains Belonging to Novel Clades MLB and VA, Are Circulating within Japanese
      Populations.
AB  - Human astroviruses (HAstVs) are a common etiological agent of infantile
      gastroenteritis. Recent studies revealed that novel astrovirus (AstV) strains of
      the MLB clade (MLB-AstVs) and VA clade (VA-AstVs), which are genetically distinct
      from the classic HAstVs, are circulating in the human population. In the present
      study, we quantified classic HAstVs as well as carried out a genetic analysis of
      classic and novel HAstVs in wastewater in Japan. The concentration of classic
      HAstVs in the influent water samples ranged from 10(4) to 10(5) copies per liter,
      and the amount removed by wastewater treatment was determined to be 2.4 +/- 0.3
      log10. Four types of classic HAstV strains (HAstV types 1, 2, 5, and 4/8) as well
      as novel AstV strains belonging to the MLB-2, VA-1, and VA-2 clades were
      identified using reverse transcription-PCR (RT-PCR) assays, including assays
      newly developed for the detection of strains of the MLB and VA clades, followed
      by cloning and nucleotide sequencing. Our results suggest that genetically
      diverse AstV strains are circulating among the human population in Japan. The
      newly developed (semi)nested RT-PCR assays for these novel AstV clades are useful
      to identify and characterize the novel AstVs in environmental waters. 

PMID- 25979885
TI  - A Versatile Family 3 Glycoside Hydrolase from Bifidobacterium adolescentis
      Hydrolyzes beta-Glucosides of the Fusarium Mycotoxins Deoxynivalenol, Nivalenol,
      and HT-2 Toxin in Cereal Matrices.
AB  - Glycosylation plays a central role in plant defense against xenobiotics,
      including mycotoxins. Glucoconjugates of Fusarium toxins, such as deoxynivalenol
      3-O-beta-d-glucoside (DON-3G), often cooccur with their parental toxins in cereal
      based food and feed. To date, only limited information exists on the occurrence
      of glucosylated mycotoxins and their toxicological relevance. Due to a lack of
      analytical standards and the requirement of high-end analytical instrumentation
      for their direct determination, hydrolytic cleavage of beta-glucosides followed
      by analysis of the released parental toxins has been proposed as an indirect
      determination approach. This study compares the abilities of several fungal and
      recombinant bacterial beta-glucosidases to hydrolyze the model analyte DON-3G.
      Furthermore, substrate specificities of two fungal and two bacterial
      (Lactobacillus brevis and Bifidobacterium adolescentis) glycoside hydrolase
      family 3 beta-glucosidases were evaluated on a broader range of substrates. The
      purified recombinant enzyme from B. adolescentis (BaBgl) displayed high
      flexibility in substrate specificity and exerted the highest hydrolytic activity
      toward 3-O-beta-d-glucosides of the trichothecenes deoxynivalenol (DON),
      nivalenol, and HT-2 toxin. A Km of 5.4 mM and a Vmax of 16 MUmol min(-1) mg(-1)
      were determined with DON-3G. Due to low product inhibition (DON and glucose) and
      sufficient activity in several extracts of cereal matrices, this enzyme has the
      potential to be used for indirect analyses of trichothecene-beta-glucosides in
      cereal samples. 

PMID- 25979886
TI  - Identification of GH15 Family Thermophilic Archaeal Trehalases That Function
      within a Narrow Acidic-pH Range.
AB  - Two glucoamylase-like genes, TVN1315 and Ta0286, from the archaea Thermoplasma
      volcanium and T. acidophilum, respectively, were expressed in Escherichia coli.
      The gene products, TVN1315 and Ta0286, were identified as archaeal trehalases.
      These trehalases belong to the CAZy database family GH15, although they have
      putative (alpha/alpha)6 barrel catalytic domain structures similar to those of
      GH37 and GH65 family trehalases from other organisms. These newly identified
      trehalases function within a narrow range of acidic pH values (pH 3.2 to 4.0) and
      at high temperatures (50 to 60 degrees C), and these enzymes display Km values
      for trehalose higher than those observed for typical trehalases. These enzymes
      were inhibited by validamycin A; however, the inhibition constants (Ki) were
      higher than those of other trehalases. Three TVN1315 mutants, corresponding to
      E408Q, E571Q, and E408Q/E571Q mutations, showed reduced activity, suggesting that
      these two glutamic acid residues are involved in trehalase catalysis in a manner
      similar to that of glucoamylase. To date, TVN1315 and Ta0286 are the first
      archaeal trehalases to be identified, and this is the first report of the
      heterologous expression of GH15 family trehalases. The identification of these
      trehalases could extend our understanding of the relationships between the
      structure and function of GH15 family enzymes as well as glycoside hydrolase
      family enzymes; additionally, these enzymes provide insight into archaeal
      trehalose metabolism. 

PMID- 25979887
TI  - Chromosome-Directed PCR-Based Detection and Quantification of Bacillus cereus
      Group Members with Focus on B. thuringiensis Serovar israelensis Active against
      Nematoceran Larvae.
AB  - Bacillus thuringiensis serovar israelensis is a wide-spread soil bacterium
      affiliated with the B. cereus group (Bcg) and is widely used in biocontrol
      products applied against mosquito and black fly larvae. For monitoring and
      quantification of applied B. thuringiensis serovar israelensis and its effect on
      indigenous B. thuringiensis serovar israelensis and Bcg assemblages, efficient
      and reliable tools are essential. The abundance and properties of B.
      thuringiensis serovar israelensis strains in the environment traditionally have
      been investigated with cultivation-dependent techniques, which are hampered by
      low sensitivity and the morphological similarity between B. cereus and B.
      thuringiensis. Currently available PCR-based detection and quantification tools
      target markers located on plasmids. In this study, a new cultivation-independent
      PCR-based method for efficient and specific quantification of B. thuringiensis
      serovar israelensis and Bcg is presented, utilizing two sets of PCR primers
      targeting the bacterial chromosome. Sequence database searches and empirical
      tests performed on target and nontarget species, as well as on bulk soil DNA
      samples, demonstrated that this diagnostic tool is specific for B. thuringiensis
      serovar israelensis and Bcg. The method will be useful for comparisons of Bcg and
      B. thuringiensis serovar israelensis abundances in the same samples. Moreover,
      the effect of B. thuringiensis serovar israelensis-based insecticide application
      on the total Bcg assemblages, including indigenous populations, can be
      investigated. This type of information is valuable in risk assessment and policy
      making for use of B. thuringiensis serovar israelensis in the environment. 

PMID- 25979888
TI  - Influence of Land Use, Nutrients, and Geography on Microbial Communities and
      Fecal Indicator Abundance at Lake Michigan Beaches.
AB  - Microbial communities within beach sand play a key role in nutrient cycling and
      are important to the nearshore ecosystem function. Escherichia coli and
      enterococci, two common indicators of fecal pollution, have been shown to persist
      in the beach sand, but little is known about how microbial community assemblages
      are related to these fecal indicator bacteria (FIB) reservoirs. We examined eight
      beaches across a geographic gradient and range of land use types and
      characterized the indigenous community structure in the water and the backshore,
      berm, and submerged sands. FIB were found at similar levels in sand at beaches
      adjacent to urban, forested, and agricultural land and in both the berm and
      backshore. However, there were striking differences in the berm and backshore
      microbial communities, even within the same beach, reflecting the very different
      environmental conditions in these beach zones in which FIB can survive. In
      contrast, the microbial communities in a particular beach zone were similar among
      beaches, including at beaches on opposite shores of Lake Michigan. The
      differences in the microbial communities that did exist within a beach zone
      correlated to nutrient levels, which varied among geographic locations. Total
      organic carbon and total phosphorus were higher in Wisconsin beach sand than in
      beach sand from Michigan. Within predominate genera, fine-scale sequence
      differences could be found that distinguished the populations from the two
      states, suggesting a biogeographic effect. This work demonstrates that microbial
      communities are reflective of environmental conditions at freshwater beaches and
      are able to provide useful information regarding long-term anthropogenic stress. 

PMID- 25979889
TI  - Oxalobacter formigenes Colonization and Oxalate Dynamics in a Mouse Model.
AB  - Animal and human studies have provided compelling evidence that colonization of
      the intestine with Oxalobacter formigenes reduces urinary oxalate excretion and
      lowers the risk of forming calcium oxalate kidney stones. The mechanism providing
      protection appears to be related to the unique ability of O. formigenes to rely
      on oxalate as a major source of carbon and energy for growth. However, much is
      not known about the factors that influence colonization and host-bacterium
      interactions. We have colonized mice with O. formigenes OxCC13 and systematically
      investigated the impacts of diets with different levels of calcium and oxalate on
      O. formigenes intestinal densities and urinary and intestinal oxalate levels.
      Measurement of intestinal oxalate levels in mice colonized or not colonized with
      O. formigenes demonstrated the highly efficient degradation of soluble oxalate by
      O. formigenes relative to other microbiota. The ratio of calcium to oxalate in
      diets was important in determining colonization densities and conditions where
      urinary oxalate and fecal oxalate excretion were modified, and the results were
      consistent with those from studies we have performed with colonized and
      noncolonized humans. The use of low-oxalate purified diets showed that 80% of
      animals retained O. formigenes colonization after a 1-week dietary oxalate
      deprivation. Animals not colonized with O. formigenes excreted two times more
      oxalate in feces than they had ingested. This nondietary source of oxalate may
      play an important role in the survival of O. formigenes during periods of dietary
      oxalate deprivation. These studies suggest that the mouse will be a useful model
      to further characterize interactions between O. formigenes and the host and
      factors that impact colonization. 

PMID- 25979890
TI  - Molybdenum Availability Is Key to Nitrate Removal in Contaminated Groundwater
      Environments.
AB  - The concentrations of molybdenum (Mo) and 25 other metals were measured in
      groundwater samples from 80 wells on the Oak Ridge Reservation (ORR) (Oak Ridge,
      TN), many of which are contaminated with nitrate, as well as uranium and various
      other metals. The concentrations of nitrate and uranium were in the ranges of 0.1
      MUM to 230 mM and <0.2 nM to 580 MUM, respectively. Almost all metals examined
      had significantly greater median concentrations in a subset of wells that were
      highly contaminated with uranium (>=126 nM). They included cadmium, manganese,
      and cobalt, which were 1,300- to 2,700-fold higher. A notable exception, however,
      was Mo, which had a lower median concentration in the uranium-contaminated wells.
      This is significant, because Mo is essential in the dissimilatory nitrate
      reduction branch of the global nitrogen cycle. It is required at the catalytic
      site of nitrate reductase, the enzyme that reduces nitrate to nitrite. Moreover,
      more than 85% of the groundwater samples contained less than 10 nM Mo, whereas
      concentrations of 10 to 100 nM Mo were required for efficient growth by nitrate
      reduction for two Pseudomonas strains isolated from ORR wells and by a model
      denitrifier, Pseudomonas stutzeri RCH2. Higher concentrations of Mo tended to
      inhibit the growth of these strains due to the accumulation of toxic
      concentrations of nitrite, and this effect was exacerbated at high nitrate
      concentrations. The relevance of these results to a Mo-based nitrate removal
      strategy and the potential community-driving role that Mo plays in contaminated
      environments are discussed. 

PMID- 25979891
TI  - Genetics and Physiology of Acetate Metabolism by the Pta-Ack Pathway of
      Streptococcus mutans.
AB  - In the dental caries pathogen Streptococcus mutans, phosphotransacetylase (Pta)
      catalyzes the conversion of acetyl coenzyme A (acetyl-CoA) to acetyl phosphate
      (AcP), which can be converted to acetate by acetate kinase (Ack), with the
      concomitant generation of ATP. A DeltaackA mutant displayed enhanced accumulation
      of AcP under aerobic conditions, whereas little or no AcP was observed in the
      Deltapta or Deltapta DeltaackA mutant. The Deltapta and Deltapta DeltaackA
      mutants also had diminished ATP pools compared to the size of the ATP pool for
      the parental or DeltaackA strain. Surprisingly, when exposed to oxidative stress,
      the Deltapta DeltaackA strain appeared to regain the capacity to produce AcP,
      with a concurrent increase in the size of the ATP pool compared to that for the
      parental strain. The DeltaackA and Deltapta DeltaackA mutants exhibited enhanced
      (p)ppGpp accumulation, whereas the strain lacking Pta produced less (p)ppGpp than
      the wild-type strain. The DeltaackA and Deltapta DeltaackA mutants displayed
      global changes in gene expression, as assessed by microarrays. All strains
      lacking Pta, which had defects in AcP production under aerobic conditions, were
      impaired in their abilities to form biofilms when glucose was the growth
      carbohydrate. Collectively, these data demonstrate the complex regulation of the
      Pta-Ack pathway and critical roles for these enzymes in processes that appear to
      be essential for the persistence and pathogenesis of S. mutans. 

PMID- 25979892
TI  - Comparative Analysis of Denitrifying Activities of Hyphomicrobium nitrativorans,
      Hyphomicrobium denitrificans, and Hyphomicrobium zavarzinii.
AB  - Hyphomicrobium spp. are commonly identified as major players in denitrification
      systems supplied with methanol as a carbon source. However, denitrifying
      Hyphomicrobium species are poorly characterized, and very few studies have
      provided information on the genetic and physiological aspects of denitrification
      in pure cultures of these bacteria. This is a comparative study of three
      denitrifying Hyphomicrobium species, H. denitrificans ATCC 51888, H. zavarzinii
      ZV622, and a newly described species, H. nitrativorans NL23, which was isolated
      from a denitrification system treating seawater. Whole-genome sequence analyses
      revealed that although they share numerous orthologous genes, these three species
      differ greatly in their nitrate reductases, with gene clusters encoding a
      periplasmic nitrate reductase (Nap) in H. nitrativorans, a membrane-bound nitrate
      reductase (Nar) in H. denitrificans, and one Nap and two Nar enzymes in H.
      zavarzinii. Concurrently with these differences observed at the genetic level,
      important differences in the denitrification capacities of these Hyphomicrobium
      species were determined. H. nitrativorans grew and denitrified at higher nitrate
      and NaCl concentrations than did the two other species, without significant
      nitrite accumulation. Significant increases in the relative gene expression
      levels of the nitrate (napA) and nitrite (nirK) reductase genes were also noted
      for H. nitrativorans at higher nitrate and NaCl concentrations. Oxygen was also
      found to be a strong regulator of denitrification gene expression in both H.
      nitrativorans and H. zavarzinii, although individual genes responded differently
      in these two species. Taken together, the results presented in this study
      highlight the potential of H. nitrativorans as an efficient and adaptable
      bacterium that is able to perform complete denitrification under various
      conditions. 

PMID- 25979893
TI  - Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian
      Population and Effects of Moringa-Supplemented Probiotic Yogurt.
AB  - The nutritional status of pregnant women is vital for healthy outcomes and is a
      concern for a large proportion of the world's population. The role of the
      microbiota in pregnancy and nutrition is a promising new area of study with
      potential health ramifications. In many African countries, maternal and infant
      death and morbidity are associated with malnutrition. Here, we assess the
      influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1,
      supplemented with Moringa plant as a source of micronutrients, on the health and
      oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an
      open-label study design, 26 subjects received yogurt daily, and 30 were untreated
      during the last two trimesters and for 1 month after birth. Samples were analyzed
      using 16S rRNA gene sequencing, and dietary recalls were recorded. Women
      initially categorized as nourished or undernourished consumed similar calories
      and macronutrients, which may explain why there was no difference in the
      microbiota at any body site. Consumption of yogurt increased the relative
      abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn
      feces but had no effect on the mother's microbiota at any body site. The
      microbiota of the oral cavity and GI tract remained stable over pregnancy, but
      the vaginal microbiota showed a significant increase in diversity leading up to
      and after birth. In summary, daily micronutrient-supplemented probiotic yogurt
      provides a safe, affordable food for pregnant women in rural Tanzania, and the
      resultant improvement in the gut microbial profile of infants is worthy of
      further study. 

PMID- 25979894
TI  - In Vivo Programmed Gene Expression Based on Artificial Quorum Networks.
AB  - The quorum sensing (QS) system, as a well-functioning population-dependent gene
      switch, has been widely applied in many gene circuits in synthetic biology. In
      our work, an efficient cell density-controlled expression system (QS) was
      established via engineering of the Vibrio fischeri luxI-luxR quorum sensing
      system. In order to achieve in vivo programmed gene expression, a synthetic
      binary regulation circuit (araQS) was constructed by assembling multiple genetic
      components, including the quorum quenching protein AiiA and the arabinose
      promoter ParaBAD, into the QS system. In vitro expression assays verified that
      the araQS system was initiated only in the absence of arabinose in the medium at
      a high cell density. In vivo expression assays confirmed that the araQS system
      presented an in vivo-triggered and cell density-dependent expression pattern.
      Furthermore, the araQS system was demonstrated to function well in different
      bacteria, indicating a wide range of bacterial hosts for use. To explore its
      potential applications in vivo, the araQS system was used to control the
      production of a heterologous protective antigen in an attenuated Edwardsiella
      tarda strain, which successfully evoked efficient immune protection in a fish
      model. This work suggested that the araQS system could program bacterial
      expression in vivo and might have potential uses, including, but not limited to,
      bacterial vector vaccines. 

PMID- 25979895
TI  - Microbial Diversity in Engineered Haloalkaline Environments Shaped by Shared
      Geochemical Drivers Observed in Natural Analogues.
AB  - Microbial communities in engineered terrestrial haloalkaline environments have
      been poorly characterized relative to their natural counterparts and are
      geologically recent in formation, offering opportunities to explore microbial
      diversity and assembly in dynamic, geochemically comparable contexts. In this
      study, the microbial community structure and geochemical characteristics of three
      geographically dispersed bauxite residue environments along a remediation
      gradient were assessed and subsequently compared with other engineered and
      natural haloalkaline systems. In bauxite residues, bacterial communities were
      similar at the phylum level (dominated by Proteobacteria and Firmicutes) to those
      found in soda lakes, oil sands tailings, and nuclear wastes; however, they
      differed at lower taxonomic levels, with only 23% of operational taxonomic units
      (OTUs) shared with other haloalkaline environments. Although being less diverse
      than natural analogues, bauxite residue harbored substantial novel bacterial
      taxa, with 90% of OTUs nonmatchable to cultured representative sequences. Fungal
      communities were dominated by Ascomycota and Basidiomycota, consistent with
      previous studies of hypersaline environments, and also harbored substantial novel
      (73% of OTUs) taxa. In bauxite residues, community structure was clearly linked
      to geochemical and physical environmental parameters, with 84% of variation in
      bacterial and 73% of variation in fungal community structures explained by
      environmental parameters. The major driver of bacterial community structure
      (salinity) was consistent across natural and engineered environments; however,
      drivers differed for fungal community structure between natural (pH) and
      engineered (total alkalinity) environments. This study demonstrates that both
      engineered and natural terrestrial haloalkaline environments host substantial
      repositories of microbial diversity, which are strongly shaped by geochemical
      drivers. 

PMID- 25979896
TI  - Prey-Specific Growth Responses of Freshwater Flagellate Communities Induced by
      Morphologically Distinct Bacteria from the Genus Limnohabitans.
AB  - Because their large growth potential is counterbalanced with grazing by
      heterotrophic nanoflagellates (HNF), bacteria of the genus Limnohabitans, which
      are common in many freshwater habitats, represent a valuable model for examining
      bacterial carbon flow to the grazer food chain. We conducted experiments with
      natural HNF communities taken from two distinct habitats, the meso-eutrophic
      Rimov Reservoir and the oligo-mesotrophic Lake Cep (South Bohemia). HNF
      communities from each habitat at distinct seasonal phases, a late April algal
      bloom and a late May clear water phase, were each fed 3 Limnohabitans strains of
      differing cell sizes. Water samples were prefiltered (5 MUm) to release natural
      HNF communities from zooplankton control and then amended with the Limnohabitans
      strains L. planktonicus II-D5 (medium sized, rod shaped), Limnohabitans sp.
      strain T6-5 (thin, long, curved rod), and Limnohabitans sp. strain 2KL-3 (large
      solenoid). Using temporal sampling and prey treatment, we determined HNF growth
      parameters such as doubling time, growth efficiency, and length of lag phase
      prior starting to exponential growth. All three Limnohabitans strains supported
      HNF growth but in significant prey-, site-, and season-dependent fashions. For
      instance, addition of the moderately large T6-5 strain yielded very rapid HNF
      growth with a short lag phase. In contrast, the curved morphology and larger cell
      size of strain 2KL-3 made this prey somewhat protected against grazing by smaller
      HNF, resulting in slower HNF growth and longer lag phases. These trends were
      particularly pronounced during the late May clear-water phase, which was
      dominated by smaller HNF cells. This may indicate a longer "adaptation time" for
      the flagellate communities toward the large prey size offered. 

PMID- 25979898
TI  - Fungal Bioweathering of Mimetite and a General Geomycological Model for Lead
      Apatite Mineral Biotransformations.
AB  - Fungi play important roles in biogeochemical processes such as organic matter
      decomposition, bioweathering of minerals and rocks, and metal transformations and
      therefore influence elemental cycles for essential and potentially toxic
      elements, e.g., P, S, Pb, and As. Arsenic is a potentially toxic metalloid for
      most organisms and naturally occurs in trace quantities in soil, rocks, water,
      air, and living organisms. Among more than 300 arsenic minerals occurring in
      nature, mimetite [Pb5(AsO4)3Cl] is the most stable lead arsenate and holds
      considerable promise in metal stabilization for in situ and ex situ sequestration
      and remediation through precipitation, as do other insoluble lead apatites, such
      as pyromorphite [Pb5(PO4)3Cl] and vanadinite [Pb5(VO4)3Cl]. Despite the
      insolubility of mimetite, the organic acid-producing soil fungus Aspergillus
      niger was able to solubilize mimetite with simultaneous precipitation of lead
      oxalate as a new mycogenic biomineral. Since fungal biotransformation of both
      pyromorphite and vanadinite has been previously documented, a new biogeochemical
      model for the biogenic transformation of lead apatites (mimetite, pyromorphite,
      and vanadinite) by fungi is hypothesized in this study by application of
      geochemical modeling together with experimental data. The models closely agreed
      with experimental data and provided accurate simulation of As and Pb complexation
      and biomineral formation dependent on, e.g., pH, cation-anion composition, and
      concentration. A general pattern for fungal biotransformation of lead apatite
      minerals is proposed, proving new understanding of ecological implications of the
      biogeochemical cycling of component elements as well as industrial applications
      in metal stabilization, bioremediation, and biorecovery. 

PMID- 25979897
TI  - Destruction of the Capsid and Genome of GII.4 Human Norovirus Occurs during
      Exposure to Metal Alloys Containing Copper.
AB  - Human norovirus (HuNoV) represents a significant public health burden worldwide
      and can be environmentally transmitted. Copper surfaces have been shown to
      inactivate the cultivable surrogate murine norovirus, but no such data exist for
      HuNoV. The purpose of this study was to characterize the destruction of GII.4
      HuNoV and virus-like particles (VLPs) during exposure to copper alloy surfaces.
      Fecal suspensions positive for a GII.4 HuNoV outbreak strain or GII.4 VLPs were
      exposed to copper alloys or stainless steel for 0 to 240 min and recovered by
      elution. HuNoV genome integrity was assessed by reverse transcription
      quantitative PCR (RT-qPCR) (without RNase treatment), and capsid integrity was
      assessed by RT-qPCR (with RNase treatment), transmission electron microscopy
      (TEM), SDS-PAGE/Western blot analysis, and a histo-blood group antigen (HBGA)
      binding assay. Exposure of fecal suspensions to pure copper for 60 min reduced
      the GII.4 HuNoV RNA copy number by ~3 log10 units when analyzed by RT-qPCR
      without RNase treatment and by 4 log10 units when a prior RNase treatment was
      used. The rate of reduction of the HuNoV RNA copy number was approximately
      proportional to the percentage of copper in each alloy. Exposure of GII.4 HuNoV
      VLPs to pure-copper surfaces resulted in noticeable aggregation and destruction
      within 240 min, an 80% reduction in the VP1 major capsid protein band intensity
      in 15 min, and a near-complete loss of HBGA receptor binding within 8 min. In all
      experiments, HuNoV remained stable on stainless steel. These results suggest that
      copper surfaces destroy HuNoV and may be useful in preventing environmental
      transmission of the virus in at-risk settings. 

PMID- 25979899
TI  - Involvement of Colonizing Bacillus Isolates in Glucovanillin Hydrolysis during
      the Curing of Vanilla planifolia Andrews.
AB  - Vanilla beans were analyzed using biochemical methods, which revealed that
      glucovanillin disperses from the inner part to the outer part of the vanilla bean
      during the curing process and is simultaneously hydrolyzed by beta-d-glucosidase.
      Enzymatic hydrolysis was found to occur on the surface of the vanilla beans.
      Transcripts of the beta-d-glucosidase gene (bgl) of colonizing microorganisms
      were detected. The results directly indicate that colonizing microorganisms are
      involved in glucovanillin hydrolysis. Phylogenetic analysis based on 16S rRNA
      gene sequences showed that the colonizing microorganisms mainly belonged to the
      Bacillus genus. bgl was detected in all the isolates and presented clustering
      similar to that of the isolate taxonomy. Furthermore, inoculation of green
      fluorescent protein-tagged isolates showed that the Bacillus isolates can
      colonize vanilla beans. Glucovanillin was metabolized as the sole source of
      carbon in a culture of the isolates within 24 h. These isolates presented unique
      glucovanillin degradation capabilities. Vanillin was the major volatile compound
      in the culture. Other compounds, such as alpha-cubebene, beta-pinene, and
      guaiacol, were detected in some isolate cultures. Colonizing Bacillus isolates
      were found to hydrolyze glucovanillin in culture, indirectly demonstrating the
      involvement of colonizing Bacillus isolates in glucovanillin hydrolysis during
      the vanilla curing process. Based on these results, we conclude that colonizing
      Bacillus isolates produce beta-d-glucosidase, which mediates glucovanillin
      hydrolysis and influences flavor formation. 

PMID- 25979901
TI  - Preliminary Validation of a New Developmental Screening Tool for
      Neurodevelopmental Delay in HIV-Infected South African Children.
AB  - Screening for developmental delays among HIV-infected children is not routine in
      most pediatric HIV clinics in Africa because of the lack of locally adaptable,
      simple, sensitive and rapid screening tools. The Division of Developmental
      Pediatrics of the Red Cross War Memorial Children's Hospital developed a tool for
      rapid screening of moderate to severe global developmental delays among HIV
      infected children aged 9 to 36 months. The diagnostic accuracy of the novel
      screening tool was evaluated. Forty-seven HIV-infected children aged 9 to 36
      months were screened using the Red Cross War Memorial Children's Hospital
      developmental screening tool. Full developmental assessments of same children
      were performed using the Bayley Scales of Infant and Toddler Development, Third
      Edition. The Red Cross War Memorial Children's Hospital tool's sensitivity was
      78.5%, specificity 54.6%, positive predictive value was 42.6%, and negative
      predictive value was 85.4%. The Red Cross War Memorial Children's Hospital
      screening tool was adequately sensitive and therefore recommended for screening
      of moderate to severe developmental delays among HIV-infected children. 

PMID- 25979900
TI  - Diversity of the Sediment Microbial Community in the Aha Watershed (Southwest
      China) in Response to Acid Mine Drainage Pollution Gradients.
AB  - Located in southwest China, the Aha watershed is continually contaminated by acid
      mine drainage (AMD) produced from upstream abandoned coal mines. The watershed is
      fed by creeks with elevated concentrations of aqueous Fe (total Fe > 1 g/liter)
      and SO4 (2-) (>6 g/liter). AMD contamination gradually decreases throughout
      downstream rivers and reservoirs, creating an AMD pollution gradient which has
      led to a suite of biogeochemical processes along the watershed. In this study,
      sediment samples were collected along the AMD pollution sites for geochemical and
      microbial community analyses. High-throughput sequencing found various bacteria
      associated with microbial Fe and S cycling within the watershed and AMD-impacted
      creek. A large proportion of Fe- and S-metabolizing bacteria were detected in
      this watershed. The dominant Fe- and S-metabolizing bacteria were identified as
      microorganisms belonging to the genera Metallibacterium, Aciditerrimonas,
      Halomonas, Shewanella, Ferrovum, Alicyclobacillus, and Syntrophobacter. Among
      them, Halomonas, Aciditerrimonas, Metallibacterium, and Shewanella have
      previously only rarely been detected in AMD-contaminated environments. In
      addition, the microbial community structures changed along the watershed with
      different magnitudes of AMD pollution. Moreover, the canonical correspondence
      analysis suggested that temperature, pH, total Fe, sulfate, and redox potentials
      (Eh) were significant factors that structured the microbial community
      compositions along the Aha watershed. 

PMID- 25979902
TI  - Patient Activity and Survival Following Implantable Cardioverter-Defibrillator
      Implantation: The ALTITUDE Activity Study.
AB  - BACKGROUND: Physical activity data are collected automatically by implantable
      cardioverter-defibrillators (ICDs). Though these data potentially provide a
      quantifiable and easily accessible measure of functional status, its relationship
      with survival has not been well studied. METHODS AND RESULTS: Patients enrolled
      in the Boston Scientific LATITUDE remote monitoring system from 2008 to 2012 with
      ICDs were eligible. Remote monitoring data were used to calculate mean daily
      activity at baseline (30 to 60 days after implantation), and longitudinally. Cox
      regression was used to examine the association between survival and increments of
      30 minutes/day in both (1) mean baseline activity and (2) time-varying activity,
      with both adjusted for demographic and device characteristics. A total of 98 437
      patients were followed for a median of 2.2 years (mean age of 67.7+/-13.1 years;
      71.7% male). Mean baseline daily activity was 107.5+/-66.2 minutes/day. The
      proportion of patients surviving after 4 years was significantly higher among
      those in the most versus least active quintile of mean baseline activity (90.5%
      vs. 50.0%; log-rank P value, <0.001). Lower mean baseline activity (i.e.,
      incremental difference of 30-minutes/day) was independently associated with a
      higher risk of death (adjusted hazard ratio [AHR], 1.44; 95% confidence interval
      [CI], 1.427 to 1.462). Time-varying activity was similarly associated with a
      higher risk of death (AHR, 1.48; 95% CI, 1.451 to 1.508), indicating that a
      patient having 30 minutes per day less activity in a given month has a 48%
      increased hazard for death when compared to a similar patient in the same month.
      CONCLUSIONS: Patient activity measured by ICDs strongly correlates with survival
      following ICD implantation.

PMID- 25979903
TI  - Recurrent deep vein thrombosis with rivaroxaban in a patient with metastatic
      testicular cancer.

PMID- 25979904
TI  - Issues associated with the economic evaluation entitled "a cost-effectiveness
      evaluation of hospital discharge counseling by pharmacists".

PMID- 25979905
TI  - Author response to "issues associated with the economic evaluation entitled "a
      cost-effectiveness evaluation of hospital discharge counseling by pharmacists".

PMID- 25979906
TI  - Presidential address: a roadmap for organizational success.

PMID- 25979911
TI  - Effects of type of light on mouse circadian behaviour and stress levels.
AB  - Light is the principal synchronizing environmental factor for the biological
      clock. Light quantity (intensity), and light quality (type of light source) can
      have different effects. The aim of this study was to determine the effects of the
      type of light experienced from the time of birth on mouse growth, circadian
      behaviour and stress levels. We raised pigmented and albino mice under 24 h light
      dark cycles of either fluorescent or white light-emitting diode (LED) light
      source during the suckling stage, and the animals were then exposed to various
      light environments after weaning and their growth rate, locomotor activity and
      plasma corticosterone concentration were measured. We found that the type of
      light the animals were exposed to did not affect the animals' growth rates or
      stress levels. However, we observed significant effects on the expression of the
      locomotor activity rhythm under low contrast light-dark cycles in pigmented mice,
      and under constant light in both albino and pigmented mice. These results
      highlight the importance of environmental light quality (light source) on
      circadian behavioural rhythms, and the need for close monitoring of light
      environments in animal facilities.

PMID- 25979912
TI  - A lotus root-like appearance in carotid stenosis on optical coherence tomography.
AB  - An 82-year-old man visited the outpatient clinic of our stroke centre because of
      dizziness. He had a previous history of stroke without definite sequelae. Severe
      stenosis in the left proximal internal carotid artery (ICA) was seen on Doppler
      sonography. Conventional angiography revealed focal severe stenosis with 'string
      sign' in the left proximal ICA and delayed distal run off. Optical coherence
      tomography showed multiple channels surrounding a narrowed central lumen (lotus
      root-like appearance). Carotid stent placement with a protection device was done
      without complications. The patient was discharged in good condition 5 days after
      the procedure.

PMID- 25979913
TI  - A preterm neonate with seizures unresponsive to conventional treatment.
AB  - The case of a patient who presented with neonatal seizures unresponsive to
      conventional antiepileptic drugs and pyridoxine is reported. The baby girl was
      subsequently treated with pyridoxal 5'-phosphate (PLP) on day 20 of life, and
      showed rapid seizure control and normal development, with only mildly abnormal
      liver function tests at the current age of 6 years. Sequencing of the
      pyridox(am)ine 5'-phosphate oxidase (PNPO) gene revealed a heterozygous insertion
      of a single base in exon 7. The second allele was found to be normal although the
      patient may carry a mutation in another gene of the vitamin B6 pathway. Follow-up
      at 6 years of age showed a seizure-free young girl (on 42 mg/kg/day PLP) with
      normal development but mild elevation of liver function tests. A high index of
      suspicion for metabolic disease must be kept in mind with neonatal seizures
      unresponsive to conventional treatment. 

PMID- 25979914
TI  - Well-described concertina effect during coronary angioplasty.

PMID- 25979915
TI  - Tricuspid valve tissue in the left ventricular outflow tract following
      ventricular septal defect repair.

PMID- 25979916
TI  - Early Lupus Project - A multicentre Italian study on systemic lupus erythematosus
      of recent onset.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with a
      high degree of variability at onset that is problematic for a correct and prompt
      diagnosis. We undertook this project with the purpose of collecting an inception
      cohort of Italian patients with recent-onset SLE, in order to obtain information
      on the main clinical and serological characteristics at the beginning of the
      disease. In this first report we describe the characteristics of this cohort at
      study entry. METHODS: All patients with a diagnosis of SLE (1997 ACR criteria)
      and a disease duration less than 12 months were consecutively enrolled between 1
      January 2012 and 31 December 2013 in a multicentre prospective study. Information
      on clinical and serological characteristics at study entry and then every six
      months was collected into a specific electronic database. Statistical analysis
      was performed by means of the Openstat program. RESULTS: Among 122 patients
      enrolled (103 F) 94.3% were Caucasians. Mean age (SD) of patients at study entry
      was 37.3 (14.3) years, mean age at disease onset was 34.8 (14.3) years, mean age
      at diagnosis was 36.9 (14.3) years, and mean disease duration was 2.9 (3.9)
      months. The frequency of the manifestations included in the 1997 ACR criteria was
      as follows: ANA 97.5%, immunologic disorders (anti-dsDNA, anti-Sm,
      antiphospholipid antibodies) 85.2%, arthritis 61.8%, haematologic disorders
      55.7%, malar rash 31.1%, photosensitivity 29.5%, serositis 27%, renal disorders
      27%, oral/nasal ulcers 11.5%, neurologic disorders 8.2%, and discoid rash 5.7%.
      The cumulative frequency of mucocutaneous symptoms was 77.8%. At enrolment,
      autoantibody frequency was: ANA 100%, anti-dsDNA 83.6%, anti-SSA 28%,
      anticardiolipin 24.5%, anti-nRNP 20.4%, anti-beta2GPI 17.2%, lupus anticoagulant
      16.3%, anti-Sm 16%, and anti-SSB 13.1%. CONCLUSIONS: In this paper we describe
      the main clinical and serological characteristics of an Italian inception cohort
      of patients with recent-onset SLE. At disease onset, mucocutaneous
      manifestations, arthritis and haematologic manifestations were the most frequent
      symptoms; ANA, anti-dsDNA and complement reduction were the most frequent
      laboratory findings. Our data confirm that the diagnosis of SLE is a challenging
      one, and that SLE is a severe disease even at onset, since the majority of
      patients require at least a hospitalization before the diagnosis.

PMID- 25979917
TI  - Strigolactone Regulates Leaf Senescence in Concert with Ethylene in Arabidopsis.
AB  - Leaf senescence is not a passive degenerative process; it represents a process of
      nutrient relocation, in which materials are salvaged for growth at a later stage
      or to produce the next generation. Leaf senescence is regulated by various
      factors, such as darkness, stress, aging, and phytohormones. Strigolactone is a
      recently identified phytohormone, and it has multiple functions in plant
      development, including repression of branching. Although strigolactone is
      implicated in the regulation of leaf senescence, little is known about its
      molecular mechanism of action. In this study, strigolactone biosynthesis mutant
      strains of Arabidopsis (Arabidopsis thaliana) showed a delayed senescence
      phenotype during dark incubation. The strigolactone biosynthesis genes MORE
      AXIALLY GROWTH3 (MAX3) and MAX4 were drastically induced during dark incubation
      and treatment with the senescence-promoting phytohormone ethylene, suggesting
      that strigolactone is synthesized in the leaf during leaf senescence. This
      hypothesis was confirmed by a grafting experiment using max4 as the stock and
      Columbia-0 as the scion, in which the leaves from the Columbia-0 scion senesced
      earlier than max4 stock leaves. Dark incubation induced the synthesis of ethylene
      independent of strigolactone. Strigolactone biosynthesis mutants showed a delayed
      senescence phenotype during ethylene treatment in the light. Furthermore, leaf
      senescence was strongly accelerated by the application of strigolactone in the
      presence of ethylene and not by strigolactone alone. These observations suggest
      that strigolactone promotes leaf senescence by enhancing the action of ethylene.
      Thus, dark-induced senescence is regulated by a two-step mechanism: induction of
      ethylene synthesis and consequent induction of strigolactone synthesis in the
      leaf. 

PMID- 25979918
TI  - Leaf evolution in early-diverging ferns: insights from a new fern-like plant from
      the Late Devonian of China.
AB  - BACKGROUND AND AIMS: With the exception of angiosperms, the main euphyllophyte
      lineages (i.e. ferns sensu lato, progymnosperms and gymnosperms) had evolved
      laminate leaves by the Late Devonian. The evolution of laminate leaves, however,
      remains unclear for early-diverging ferns, largely represented by fern-like
      plants. This study presents a novel fern-like taxon with pinnules, which provides
      new insights into the early evolution of laminate leaves in early-diverging
      ferns. METHODS: Macrofossil specimens were collected from the Upper Devonian
      (Famennian) Wutong Formation of Anhui and Jiangsu Provinces, South China. A
      standard degagement technique was employed to uncover compressed plant portions
      within the rock matrix. KEY RESULTS: A new fern-like taxon, SHOUGANGIA BELLA GEN
      ET SP NOV: , is described and represents an early-diverging fern with highly
      derived features. It has a partially creeping stem with adventitious roots only
      on one side, upright primary and secondary branches arranged in helices, tertiary
      branches borne alternately or (sub)oppositely, laminate and usually lobed leaves
      with divergent veins, and complex fertile organs terminating tertiary branches
      and possessing multiple divisions and numerous terminal sporangia. CONCLUSIONS:
      Shougangia bella provides unequivocal fossil evidence for laminate leaves in
      early-diverging ferns. It suggests that fern-like plants, along with other
      euphyllophyte lineages, had independently evolved megaphylls by the Late
      Devonian, possibly in response to a significant decline in atmospheric CO2
      concentration. Among fern-like plants, planate ultimate appendages are homologous
      with laminate pinnules, and in the evolution of megaphylls, fertile organs tend
      to become complex.

PMID- 25979920
TI  - Efficacy of Two Cleaning Solutions for the Decontamination of 10 Antineoplastic
      Agents in the Biosafety Cabinets of a Hospital Pharmacy.
AB  - OBJECTIVE: This study aimed to evaluate two cleaning solutions for the chemical
      decontamination of antineoplastic agents on the surfaces of two biosafety
      cabinets routinely used for chemotherapy preparation in a hospital pharmacy.
      METHODS: For almost 1 year (49 weeks), two different solutions were used for the
      weekly cleaning of two biosafety cabinets in a hospital pharmacy's centralized
      cytotoxic preparation unit. The solutions evaluated were a commercial solution of
      isopropyl alcohol (IPA) and water (70:30, vol:vol), and a detergent solution
      constituted by 10(-2)M of sodium dodecyl sulfate (SDS) with 20% IPA. Seven areas
      in each biosafety cabinet were wiped 14 times throughout the year, before and
      after the weekly cleaning process, according to a validated procedure. Samples
      were analyzed using a validated method of high-performance liquid chromatography
      coupled to mass spectrometry. The decontamination efficacy of these two solutions
      was tested for 10 antineoplastic agents: cytarabine, gemcitabine, methotrexate,
      etoposide phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin,
      epirubicin, and vincristine. RESULTS: Overall decontamination efficacies observed
      were 82+/-6% and 49+/-11% for SDS solution and IPA, respectively. Higher
      contamination levels were distributed on areas frequently touched by the pharmacy
      technicians-such as sleeves and airlock handles-than on scale plates, gravimetric
      control hardware, and work benches. Detected contaminations of cyclophosphamide,
      ifosfamide, gemcitabine, and cytarabine were higher than those of the others
      agents. SDS solution was almost 20% more efficient than IPA on eight of the
      antineoplastic agents. CONCLUSION: Both cleaning solutions were able to reduce
      contamination levels in the biosafety cabinets. The efficacy of the solution
      containing an anionic detergent agent (SDS) was shown to be generally higher than
      that of IPA and, after the SDS cleaning procedure, biosafety cabinets
      demonstrated acceptable contamination levels.

PMID- 25979919
TI  - The effect of polyploidy and hybridization on the evolution of floral colour in
      Nicotiana (Solanaceae).
AB  - BACKGROUND AND AIMS: Speciation in angiosperms can be accompanied by changes in
      floral colour that may influence pollinator preference and reproductive
      isolation. This study investigates whether changes in floral colour can accompany
      polyploid and homoploid hybridization, important processes in angiosperm
      evolution. METHODS: Spectral reflectance of corolla tissue was examined for 60
      Nicotiana (Solanaceae) accessions (41 taxa) based on spectral shape
      (corresponding to pigmentation) as well as bee and hummingbird colour perception
      in order to assess patterns of floral colour evolution. Polyploid and homoploid
      hybrid spectra were compared with those of their progenitors to evaluate whether
      hybridization has resulted in floral colour shifts. KEY RESULTS: Floral colour
      categories in Nicotiana seem to have arisen multiple times independently during
      the evolution of the genus. Most younger polyploids displayed an unexpected
      floral colour, considering those of their progenitors, in the colour perception
      of at least one pollinator type, whereas older polyploids tended to resemble one
      or both of their progenitors. CONCLUSIONS: Floral colour evolution in Nicotiana
      is weakly constrained by phylogeny, and colour shifts do occur in association
      with both polyploid and homoploid hybrid divergence. Transgressive floral colour
      in N. tabacum has arisen by inheritance of anthocyanin pigmentation from its
      paternal progenitor while having a plastid phenotype like its maternal
      progenitor. Potentially, floral colour evolution has been driven by, or resulted
      in, pollinator shifts. However, those polyploids that are not sympatric (on a
      regional scale) with their progenitor lineages are typically not divergent in
      floral colour from them, perhaps because of a lack of competition for
      pollinators.

PMID- 25979921
TI  - Increased life expectancy for physically active Norwegians.

PMID- 25979922
TI  - Statistical controversies in clinical research: scientific and ethical problems
      with adaptive randomization in comparative clinical trials.
AB  - BACKGROUND: In recent years, various outcome adaptive randomization (AR) methods
      have been used to conduct comparative clinical trials. Rather than randomizing
      patients equally between treatments, outcome AR uses the accumulating data to
      unbalance the randomization probabilities in favor of the treatment arm that
      currently is superior empirically. This is motivated by the idea that, on
      average, more patients in the trial will be given the treatment that is truly
      superior, so AR is ethically more desirable than equal randomization. AR remains
      controversial, however, and some of its properties are not well understood by the
      clinical trials community. MATERIALS AND METHODS: Computer simulation was used to
      evaluate properties of a 200-patient clinical trial conducted using one of four
      Bayesian AR methods and compare them to an equally randomized group sequential
      design. RESULTS: Outcome AR has several undesirable properties. These include a
      high probability of a sample size imbalance in the wrong direction, which might
      be surprising to nonstatisticians, wherein many more patients are assigned to the
      inferior treatment arm, the opposite of the intended effect. Compared with an
      equally randomized design, outcome AR produces less reliable final inferences,
      including a greatly overestimated actual treatment effect difference and smaller
      power to detect a treatment difference. This estimation bias becomes much larger
      if the prognosis of the accrued patients either improves or worsens
      systematically during the trial. CONCLUSIONS: AR produces inferential problems
      that decrease potential benefit to future patients, and may decrease benefit to
      patients enrolled in the trial. These problems should be weighed against its
      putative ethical benefit. For randomized comparative trials to obtain
      confirmatory comparisons, designs with fixed randomization probabilities and
      group sequential decision rules appear to be preferable to AR, scientifically,
      and ethically.

PMID- 25979924
TI  - CCR 20th Anniversary Commentary: Expanding the Epigenetic Therapeutic Portfolio.
AB  - Epigenetic targets have emerged as an exciting area for drug discovery. The
      discovery that histone deacetylase (HDAC) inhibitors had marked anticancer
      activity in T-cell lymphoma gave impetus to the field. In a phase I study
      published in Clinical Cancer Research in March 2002, romidepsin (depsipeptide), a
      potent HDAC inhibitor, was found to be tolerable, with a side effect profile that
      was later understood to be characteristic of this class of agents. Evidence of
      activity in this key phase I trial provided momentum for the further study of
      epigenetic agents.

PMID- 25979925
TI  - CCR 20th Anniversary Commentary: Vorinostat-Gateway to Epigenetic Therapy.
AB  - The study by Kelly and colleagues, published in the September 1, 2003, issue of
      Clinical Cancer Research, established the safety and biologic activity of the
      first-in-class histone deacetylase inhibitor, vorinostat, which was administered
      intravenously. Subsequent studies led to the development of oral vorinostat and
      the regulatory approval of vorinostat for cutaneous T-cell lymphomas, which
      opened the door for the next generation of inhibitors.

PMID- 25979926
TI  - Quit early, quit often.

PMID- 25979927
TI  - Lung cancer in the era of precision medicine.
AB  - The past decade has been transformative for lung cancer patients, physicians, and
      scientists. The discovery of EGFR mutations that confer sensitivity to tyrosine
      kinase inhibitors in lung adenocarcinomas in 2004 heralded the beginning of the
      era of precision medicine for lung cancer. Indeed, it precipitated concerted
      efforts by many investigators to define molecular subgroups of lung cancer,
      characterize the genomic landscape of lung cancer subtypes, identify novel
      therapeutic targets, and define mechanisms of sensitivity and resistance to
      targeted therapies. The fruits of these efforts are visible every day now in lung
      cancer clinics: Patients receive molecular testing to determine whether their
      tumor harbors an actionable mutation, new and improved targeted therapies that
      can overcome resistance to first-generation drugs are in clinical trials, and
      drugs targeting the immune system are showing activity in patients. This
      extraordinary promise is tempered by the sobering fact that even the newest
      treatments for metastatic disease are rarely curative and are effective only in a
      small fraction of all patients. Ongoing and future efforts to find new
      vulnerabilities of lung cancers, unravel the complexity of drug resistance,
      increase the efficacy of immunotherapies, and perform biomarker-driven clinical
      trials are necessary to improve outcomes for patients with lung cancer.

PMID- 25979928
TI  - EGFR: The Paradigm of an Oncogene-Driven Lung Cancer.
AB  - Somatic, activating mutations in EGFR identify a significant minority of patients
      with non-small cell lung cancer (NSCLC). Although these mutations are associated
      with an approximately 70% response rate to some EGFR tyrosine kinase inhibitors
      (gefitinib, erlotinib, and afatinib), patients develop resistance (i.e.,
      "acquired resistance") after a median of 9 to 12 months. In patients with
      clinical acquired resistance, repeat biopsy of tumors has identified a number of
      relevant mechanisms of resistance, but by far the most frequent event is the
      acquisition of EGFR T790M, a mutation in the "gatekeeper" residue that confers
      resistance to gefitinib, erlotinib, and afatinib. This emphasizes the critical
      dependence upon EGFR signaling for some tumors, a property that has been
      exploited therapeutically. Dual EGFR blockade using afatinib and cetuximab led to
      a 29% radiographic response rate. More recently, drugs that target EGFR T790M
      (e.g., rociletinib, AZD9291, and others) have entered clinical trials, with
      impressive results observed in phase I clinical trials. The development of these
      newer drugs, with efficacy after resistance to first-line EGFR tyrosine kinase
      inhibitor, has led to exploration of these strategies in multiple disease
      settings: at resistance, in the first line, and in adjuvant treatment of those
      with completely resected early-stage disease who would otherwise die of
      recurrent/metastatic disease. This example of translational research that
      identifies mechanisms of resistance to first-generation drugs, and then targets
      those mechanisms yielding clinical benefit, is a paradigm for how targeted
      therapies can be developed.

PMID- 25979930
TI  - Squamous cell lung cancer: from tumor genomics to cancer therapeutics.
AB  - Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer
      research. For the past several years, therapeutic progress in SCC has lagged
      behind the now more common non-small cell lung cancer histologic subtype of
      adenocarcinoma. However, recent efforts to define the complex biology underlying
      SCC have begun to bear fruit in a multitude of ways, including characterization
      of previously unknown genomic and signaling pathways, delineation of new,
      potentially actionable molecular targets, and subsequent development of a large
      number of agents directed against unique SCC-associated molecular abnormalities.
      For the first time, SCC-specific prognostic gene signatures and predictive
      biomarkers of new therapeutic agents are emerging. In addition, recent and
      ongoing clinical trials, including the Lung-MAP master protocol, have been
      designed to facilitate approval of targeted therapy-biomarker combinations. In
      this comprehensive review, we describe the current status of SCC therapeutics,
      recent advances in the understanding of SCC biology and prognostic gene
      signatures, and the development of innovative new clinical trials, all of which
      offer new hope for patients with advanced SCC.

PMID- 25979932
TI  - Immune checkpoint modulation for non-small cell lung cancer.
AB  - Therapies targeting immune checkpoints have recently shown encouraging activity
      in patients with heavily pretreated advanced non-small cell lung cancer (NSCLC),
      independently of NSCLC histology or mutational status, with low toxicity profiles
      when used as monotherapy. Objective response rates of approximately 20% have been
      reported in patients with advanced NSCLC treated with antagonist antibodies
      targeting the immune checkpoint, programmed death 1 (PD-1) on activated T cells,
      or its primary ligand, programmed death ligand 1 (PD-L1) expressed within the
      tumor microenvironment. Response rates appear to be higher in patients with tumor
      PD-L1 expression documented by immunohistochemistry, although responses have been
      appreciated in patients with reportedly PD-L1-negative tumor specimens.
      Antibodies directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4),
      another immunosuppressive T-cell signaling molecule, are also being evaluated in
      clinical trials, with one randomized phase II trial demonstrating improved immune
      related progression-free survival in lung cancer patients when added to standard
      chemotherapy. Additional clinical trials are combining anti-CTLA-4 antibodies
      with either anti-PD-1 or anti-PD-L1 antibodies. Combinations of other immune
      checkpoint antagonists or agonist antibodies with anti-PD-1 or anti-PD-L1
      antibodies are also being pursued.

PMID- 25979929
TI  - Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: a paradigm
      for precision cancer medicine.
AB  - The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase was initially
      discovered as a component of the fusion protein nucleophosmin (NPM)-ALK in
      anaplastic large-cell lymphoma (ALCL). Genomic alterations in ALK, including
      rearrangements, point mutations, and genomic amplification, have now been
      identified in several malignancies, including lymphoma, non-small cell lung
      cancer (NSCLC), neuroblastoma, inflammatory myofibroblastic tumor, and others.
      Importantly, ALK serves as a validated therapeutic target in these diseases.
      Several ALK tyrosine kinase inhibitors (TKI), including crizotinib, ceritinib,
      and alectinib, have been developed, and some of them have already been approved
      for clinical use. These ALK inhibitors have all shown remarkable clinical
      outcomes in ALK-rearranged NSCLC. Unfortunately, as is the case for other kinase
      inhibitors in clinical use, sensitive tumors inevitably relapse due to acquired
      resistance. This review focuses on the discovery, function, and therapeutic
      targeting of ALK, with a particular focus on ALK-rearranged NSCLC.

PMID- 25979933
TI  - Correction: ceritinib for the treatment of late-stage (metastatic) non-small cell
      lung cancer.

PMID- 25979931
TI  - Small cell lung cancer: will recent progress lead to improved outcomes?
AB  - Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with a
      unique natural history characterized by a short doubling time, high growth
      fraction, and early development of widespread metastases. Although a chemotherapy
      and radiation-sensitive disease, SCLC typically recurs rapidly after primary
      treatment, with only 6% of patients surviving 5 years from diagnosis. This
      disease has been notable for the absence of major improvements in its treatment:
      Nearly four decades after the introduction of a platinum-etoposide doublet,
      therapeutic options have remained virtually unchanged, with correspondingly
      little improvement in survival rates. Here, we summarize specific barriers and
      challenges inherent to SCLC research and care that have limited progress in novel
      therapeutic development to date. We discuss recent progress in basic and
      translational research, especially in the development of mouse models, which will
      provide insights into the patterns of metastasis and resistance in SCLC.
      Opportunities in clinical research aimed at exploiting SCLC biology are reviewed,
      with an emphasis on ongoing trials. SCLC has been described as a recalcitrant
      cancer, for which there is an urgent need for accelerated progress. The NCI
      convened a panel of laboratory and clinical investigators interested in SCLC with
      a goal of defining consensus recommendations to accelerate progress in the
      treatment of SCLC, which we summarize here.

PMID- 25979934
TI  - Right ventricular dysfunction in children and adolescents conceived by assisted
      reproductive technologies.
AB  - Assisted reproductive technologies (ART) predispose the offspring to vascular
      dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently,
      cardiac remodeling and dysfunction during fetal and early postnatal life have
      been reported in offspring of ART, but it is not known whether these cardiac
      alterations persist later in life and whether confounding factors contribute to
      this problem. We, therefore, assessed cardiac function and pulmonary artery
      pressure by echocardiography in 54 healthy children conceived by ART (mean age
      11.5 +/- 2.4 yr) and 54 age-matched (12.2 +/- 2.3 yr) and sex-matched control
      children. Because ART is often associated with low birth weight and prematurity,
      two potential confounders associated with cardiac dysfunction, only singletons
      born with normal birth weight at term were studied. Moreover, because cardiac
      remodeling in infants conceived by ART was observed in utero, a situation
      associated with increased right heart load, we also assessed cardiac function
      during high-altitude exposure, a condition associated with hypoxic pulmonary
      hypertension-induced right ventricular overload. We found that, while at low
      altitude cardiac morphometry and function was not different between children
      conceived by ART and control children, under the stressful conditions of high
      altitude-induced pressure overload and hypoxia, larger right ventricular end
      diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue
      Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid
      annulus) were detectable in children and adolescents conceived by ART. In
      conclusion, right ventricular dysfunction persists in children and adolescents
      conceived by ART. These cardiac alterations appear to be related to ART per se
      rather than to low birth weight or prematurity. 

PMID- 25979935
TI  - Plasma arginine metabolites reflect airway dysfunction in a murine model of
      allergic airway inflammation.
AB  - L-arginine metabolism is important in the maintenance of airway tone. Shift of
      metabolism from the nitric oxide synthase to arginase pathways contributes to the
      increased airway responsiveness in asthma. We tested the hypothesis that systemic
      levels of L-arginine metabolites are biomarkers reflective of airway dysfunction.
      We used a mouse model of acute allergic airway inflammation to OVA that manifests
      with significant airway hyperresponsiveness to methacholine. To determine tissue
      arginase activity in vivo, the isotopic enrichment of an infused L-arginine
      stable isotope and its product amino acid L-ornithine were measured in lung and
      airway homogenates using liquid chromatography-tandem mass spectrometry. Tissue
      and plasma concentrations of other L-arginine metabolites, including L-citrulline
      and symmetric and asymmetric dimethylarginine, were measured and correlated with
      lung arginase activity and methacholine responsiveness of the airways. The
      effectiveness of intratracheal instillation of an arginase inhibitor
      (boronoethylcysteine) on pulmonary arginase activity and circulating
      concentrations of L-arginine metabolites was also studied. We demonstrate that 1)
      plasma indexes of L-arginine bioavailability and impairment of nitric oxide
      synthase function correlate with airway responsiveness to methacholine; 2) plasma
      levels of L-ornithine predict in vivo pulmonary arginase activity and airway
      function; and 3) acute arginase inhibition reduces in vivo pulmonary arginase
      activity to control levels and normalizes plasma L-ornithine, but not L-arginine,
      bioavailability in this model. We conclude that plasma L-ornithine may be useful
      as a systemic biomarker to predict responses to therapeutic interventions
      targeting airway arginase in asthma.

PMID- 25979936
TI  - Estrogen inhibits lysyl oxidase and decreases mechanical function in engineered
      ligaments.
AB  - Women are more likely to suffer an anterior cruciate ligament (ACL) rupture than
      men, and the incidence of ACL rupture in women rises with increasing estrogen
      levels. We used an engineered ligament model to determine how an acute rise in
      estrogen decreases the mechanical properties of ligaments. Using fibroblasts
      isolated from human ACLs from male or female donors, we engineered ligaments and
      determined that ligaments made from female ACL cells had more collagen and were
      equal in strength to those made from male ACL cells. We then treated engineered
      ligaments for 14 days with low (5 pg/ml), medium (50 pg/ml), or high (500 pg/ml)
      estrogen, corresponding to the range of in vivo serum estrogen concentrations and
      found that collagen within the grafts increased without a commensurate increase
      in mechanical strength. Mimicking the menstrual cycle, with 12 days of low
      estrogen followed by 2 days of physiologically high estrogen, resulted in a
      decrease in engineered ligament mechanical function with no change in the amount
      of collagen in the graft. The decrease in mechanical stiffness corresponded with
      a 61.7 and 76.9% decrease in the activity of collagen cross-linker lysyl oxidase
      with 24 and 48 h of high estrogen, respectively. Similarly, grafts treated with
      the lysyl oxidase inhibitor beta-aminoproprionitrile (BAPN) for 24 h showed a
      significant decrease in ligament mechanical strength [control (CON) = 1.58 +/-
      0.06 N; BAPN = 1.06 +/- 0.13 N] and stiffness (CON = 7.7 +/- 0.46 MPa; BAPN = 6.1
      +/- 0.71 MPa) without changing overall collagen levels (CON = 396 +/- 11.5 MUg;
      BAPN = 382 +/- 11.6 MUg). Together, these data suggest that the rise in estrogen
      during the follicular phase decreases lysyl oxidase activity in our engineered
      ligament model and if this occurs in vivo may decrease the stiffness of ligaments
      and contribute to the elevated rate of ACL rupture in women. 

PMID- 25979937
TI  - Commentaries on Viewpoint: The two-hour marathon: what's the equivalent for
      women?

PMID- 25979938
TI  - Last Word on Viewpoint: The two-hour marathon: What's the equivalent for women?

PMID- 25979939
TI  - Corrigendum.

PMID- 25979940
TI  - Classical conditioning of analgesic and hyperalgesic pain responses without
      conscious awareness.
AB  - Pain reduction and enhancement can be produced by means of conditioning
      procedures, yet the role of awareness during the acquisition stage of classical
      conditioning is unknown. We used psychophysical measures to establish whether
      conditioned analgesic and hyperalgesic responses could be acquired by unseen
      (subliminally presented) stimuli. A 2 * 2 factorial design, including
      subliminal/supraliminal exposures of conditioning stimuli (CS) during
      acquisition/extinction, was used. Results showed significant analgesic and
      hyperalgesic responses (P < 0.001), and responses were independent of CS
      awareness, as subliminal/supraliminal cues during acquisition/extinction led to
      comparable outcomes. The effect was significantly larger for hyperalgesic than
      analgesic responses (P < 0.001). Results demonstrate that conscious awareness of
      the CS is not required during either acquisition or extinction of conditioned
      analgesia or hyperalgesia. Our results support the notion that nonconscious
      stimuli have a pervasive effect on human brain function and behavior and may
      affect learning of complex cognitive processes such as psychologically mediated
      analgesic and hyperalgesic responses. 

PMID- 25979942
TI  - Correction for Thavandiran et al., Design and formulation of functional
      pluripotent stem cell-derived cardiac microtissues.

PMID- 25979943
TI  - Reply to Backes and Keller: Identification of novel tissue-specific and primate
      specific human microRNAs.

PMID- 25979944
TI  - Reanalysis of 3,707 novel human microRNA candidates.

PMID- 25979946
TI  - Multitrait-Multimethod Analysis of the Strengths and Difficulties Questionnaire
      in Young Asian American Children.
AB  - The Strengths and Difficulties Questionnaire (SDQ) is a widely used
      psychopathology screening tool that measures children's emotional symptoms, peer
      problems, conduct problems, hyperactivity/inattention, and prosocial behavior.
      Previous psychometric studies of the SDQ focused primarily on older children in
      Western cultures and suffered from several methodological limitations. This study
      examined the reliability, factor structure, convergent, and discriminant validity
      of the SDQ by focusing on young Asian American children and using more rigorous
      methods. The five-factor structure of the SDQ was confirmed by confirmatory
      factor analysis. The omega coefficients indicated adequate reliability for all
      subscales except parent-rated peer problems and conduct problems. The correlated
      trait-correlated method minus one multitrait-multimethod model provided evidence
      for convergent validity and discriminant validity of all subscales except for
      conduct problems relative to hyperactivity/inattention. This study provided new
      evidence for the psychometric properties of the SDQ in young children and
      cultural suitability of the SDQ for Asian Americans.

PMID- 25979945
TI  - The comparative effectiveness of oral versus subcutaneous methotrexate for the
      treatment of early rheumatoid arthritis.
AB  - OBJECTIVE: To determine the comparative effectiveness of oral versus subcutaneous
      methotrexate (MTX) as initial therapy for patients with early rheumatoid
      arthritis (ERA). METHODS: Patients with ERA (symptoms <=1 year) initiating MTX
      therapy were included from a multicentre, prospective cohort study. We compared
      the effectiveness between starting with oral versus subcutaneous MTX over the
      first year. Longitudinal multivariable models, adjusted for potential baseline
      and time-varying confounders, were used to compare treatment changes due to
      inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS
      28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ
      DI)). RESULTS: 666 patients were included (417 oral MTX, 249 subcutaneous MTX).
      Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean
      dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients
      initially treated with subcutaneous MTX had changed treatment compared with 77%
      treated with oral MTX. After adjusting for potential confounders, subcutaneous
      MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55
      (0.39 to 0.79)). Most treatment failures were due to inefficacy with no
      difference in failure due to toxicity. In multivariable models, subcutaneous MTX
      was also associated with lower average DAS-28 scores (mean difference (-0.38 (95%
      CI -0.64 to -0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI
      1.1 to 1.3)). There was no significant difference in sustained remission or HAQ
      DI (p values 0.43 and 0.75). CONCLUSIONS: Initial treatment with subcutaneous MTX
      was associated with lower rates of treatment changes, no difference in toxicity
      and some improvements in disease control versus oral MTX over the first year in
      patients with ERA.

PMID- 25979949
TI  - Dicer1 imparts essential survival cues in Notch-driven T-ALL via miR-21-mediated
      tumor suppressor Pdcd4 repression.
AB  - The modulatory function of individual microRNAs (miRNAs) in Notch-driven T-cell
      acute lymphoblastic leukemias (T-ALLs) has recently been established. Although
      protumorigenic and tumor-suppressive miRNAs are implicated in disease onset in
      murine models of Notch-driven T-cell leukemia, whether Dicer1-processed miRNAs
      are essential for Notch-driven T-ALL is currently unknown. Here we used
      conditional and inducible genetic loss-of-function approaches to test whether the
      development and maintenance of Notch-driven T-ALL was dependent on Dicer1
      function. Mice with specific inactivation of both Dicer1 alleles in the T-cell
      lineage did not develop Notch-driven T-ALL. In contrast, loss of 1 functional
      Dicer1 allele did not significantly perturb T-ALL onset and tumor progression.
      Inducible inactivation of Dicer1 in early stage polyclonal T-ALL cells was
      sufficient to abrogate T-ALL progression in leukemic mice, whereas late-stage
      monoclonal T-ALL cells were counterselected against loss of Dicer1. Lineage
      tracing experiments revealed that Dicer1 deficiency led to the induction of
      apoptosis in T-ALL cells, whereas cell cycle progression remained unaltered.
      Through microarray-based miRNA profiling, we identified miR-21 as a previously
      unrecognized miRNA deregulated in both mouse and human T-ALL. Herein, we
      demonstrate that miR-21 regulates T-ALL cell survival via repression of the tumor
      suppressor Pdcd4. 

PMID- 25979947
TI  - Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging
      related immune defects in the Eu-TCL1 CLL mouse model.
AB  - T-cell defects, immune suppression, and poor antitumor immune responses are
      hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory
      signaling has emerged as a major immunosuppressive mechanism. However, the effect
      of different microenvironments and the confounding influence of aging are poorly
      understood. The current study uses the EMU-TCL1 mouse model, which replicates
      human T-cell defects, as a preclinical platform to longitudinally examine
      patterns of T-cell dysfunction alongside developing CLL and in different
      microenvironments, with a focus on PD-1/PD-L1 interactions. The development of
      CLL was significantly associated with changes in T-cell phenotype across all
      organs and function. Although partly mirrored in aging wild-type mice, CLL
      specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1
      and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T
      cells from leukemic and aging healthy mice highly expressed PD-1, identifying
      aging as a confounder, but adoptive transfer experiments demonstrated CLL
      specific PD-1 induction. Direct comparisons of PD-1 expression and function
      between aging CLL mice and controls identified PD-1(+) T cells in CLL as a
      heterogeneous population with variable effector function. This is highly relevant
      for therapeutic targeting of CD8(+) T cells, showing the potential of
      reprogramming and selective subset expansion to restore antitumor immunity. 

PMID- 25979948
TI  - Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by
      facilitating LCR/gamma-globin looping.
AB  - Induction of fetal hemoglobin (HbF) production in adult erythrocytes can reduce
      the severity of sickle cell disease and beta-thalassemia. Transcription of beta
      globin genes is regulated by the distant locus control region (LCR), which is
      brought into direct gene contact by the LDB1/GATA-1/TAL1/LMO2-containing complex.
      Inhibition of G9a H3K9 methyltransferase by the chemical compound UNC0638
      activates fetal and represses adult beta-globin gene expression in adult human
      hematopoietic precursor cells, but the underlying mechanisms are unclear. Here we
      studied UNC0638 effects on beta-globin gene expression using ex vivo
      differentiation of CD34(+) erythroid progenitor cells from peripheral blood of
      healthy adult donors. UNC0638 inhibition of G9a caused dosed accumulation of HbF
      up to 30% of total hemoglobin in differentiated cells. Elevation of HbF was
      associated with significant activation of fetal gamma-globin and repression of
      adult beta-globin transcription. Changes in gene expression were associated with
      widespread loss of H3K9me2 in the locus and gain of LDB1 complex occupancy at the
      gamma-globin promoters as well as de novo formation of LCR/gamma-globin contacts.
      Our findings demonstrate that G9a establishes epigenetic conditions preventing
      activation of gamma-globin genes during differentiation of adult erythroid
      progenitor cells. In this view, manipulation of G9a represents a promising
      epigenetic approach for treatment of beta-hemoglobinopathies. 

PMID- 25979950
TI  - Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and
      clinically distinct syndrome.
AB  - Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture
      and pathogenesis remain uncertain. We identified 10 patients with metastatic
      cancer (7 pathologically proven) who developed severe venous limb ischemia
      (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8
      patients, cancer was not known or suspected at presentation. The patients
      exhibited a novel, clinically distinct syndrome: warfarin-associated
      supratherapeutic international normalized ratio (INR; median, 6.5) at onset of
      limb ischemia, rising platelet count during heparin anticoagulation, and platelet
      fall after stopping heparin. Despite supratherapeutic INRs, patient plasma
      contained markedly elevated thrombin-antithrombin (TAT) complex levels
      (indicating uncontrolled thrombin generation) and protein C (PC) depletion; this
      profile resembles the greatly elevated TAT/PC activity ratios reported in
      patients with warfarin-associated VLG complicating heparin-induced
      thrombocytopenia. Analyses of vitamin K-dependent factors in 6 cancer patients
      with available serial plasma samples showed that variations in the INR
      corresponded most closely with changes in factor VII, with a highly collinear
      relationship between VII and PC. We conclude that venous limb ischemia/gangrene
      is explained in some cancer patients by profoundly disturbed procoagulant
      anticoagulant balance, whereby warfarin fails to block cancer-associated
      hypercoagulability while nonetheless contributing to severe PC depletion,
      manifest as a characteristic supratherapeutic INR caused by parallel severe
      factor VII depletion. 

PMID- 25979951
TI  - P-selectin promotes neutrophil extracellular trap formation in mice.
AB  - Neutrophil extracellular traps (NETs) can be released in the vasculature. In
      addition to trapping microbes, they promote inflammatory and thrombotic diseases.
      Considering that P-selectin induces prothrombotic and proinflammatory signaling,
      we studied the role of this selectin in NET formation. NET formation (NETosis)
      was induced by thrombin-activated platelets rosetting with neutrophils and was
      inhibited by anti-P-selectin aptamer or anti-P-selectin glycoprotein ligand-1
      (PSGL-1) inhibitory antibody but was not induced by platelets from P-selectin(-/
      ) mice. Moreover, NETosis was also promoted by P-selectin-immunoglobulin fusion
      protein but not by control immunoglobulin. We isolated neutrophils from mice
      engineered to overproduce soluble P-selectin (P-selectin(DeltaCT/DeltaCT) mice).
      Although the levels of circulating DNA and nucleosomes (indicative of spontaneous
      NETosis) were normal in these mice, basal neutrophil histone citrullination and
      presence of P-selectin on circulating neutrophils were elevated. NET formation
      after stimulation with platelet activating factor, ionomycin, or phorbol 12
      myristate 13-acetate was significantly enhanced, indicating that the P
      selectin(DeltaCT/DeltaCT) neutrophils were primed for NETosis. In summary, P
      selectin, cellular or soluble, through binding to PSGL-1, promotes NETosis,
      suggesting that this pathway is a potential therapeutic target for NET-related
      diseases. 

PMID- 25979952
TI  - Preanalytical variables affecting the integrity of human biospecimens in
      biobanking.
AB  - BACKGROUND: Most errors in a clinical chemistry laboratory are due to
      preanalytical errors. Preanalytical variability of biospecimens can have
      significant effects on downstream analyses, and controlling such variables is
      therefore fundamental for the future use of biospecimens in personalized medicine
      for diagnostic or prognostic purposes. CONTENT: The focus of this review is to
      examine the preanalytical variables that affect human biospecimen integrity in
      biobanking, with a special focus on blood, saliva, and urine. Cost efficiency is
      discussed in relation to these issues. SUMMARY: The quality of a study will
      depend on the integrity of the biospecimens. Preanalytical preparations should be
      planned with consideration of the effect on downstream analyses. Currently such
      preanalytical variables are not routinely documented in the biospecimen research
      literature. Future studies using biobanked biospecimens should describe in detail
      the preanalytical handling of biospecimens and analyze and interpret the results
      with regard to the effects of these variables.

PMID- 25979953
TI  - High-sensitivity cardiac troponin t concentrations below the limit of detection
      to exclude acute myocardial infarction: a prospective evaluation.
AB  - BACKGROUND: Initial reports suggest that concentrations of high-sensitivity
      cardiac troponin T (hs-cTnT) (Roche Diagnostics Elecsys((r))) below the limit of
      blank (LoB) (3 ng/L) or limit of detection (LoD) (5 ng/L) of the assay have
      almost 100% negative predictive value (NPV) for acute myocardial infarction
      (AMI), particularly among patients without electrocardiograph (ECG) evidence of
      ischemia. We aimed to prospectively validate those findings. METHODS: We included
      adults presenting to the emergency department with suspected cardiac chest pain.
      Standard troponin T (cTnT) and hs-cTnT (both Roche Elecsys) were tested in
      samples drawn on arrival. The primary outcome was AMI, adjudicated by 2
      investigators on the basis of clinical data and >=12-h cTnT testing. We also
      evaluated diagnostic performance when AMI was readjudicated on the basis of hs
      cTnT (>=12-h) concentrations. RESULTS: Of 463 patients included, 79 (17.1%) had
      AMI. Twenty-four patients (5.2%) had hs-cTnT concentrations below the LoB,
      although none had AMI. Ninety-six patients (20.7%) had hs-cTnT concentrations
      below the LoD, 1 of whom had AMI. Thus, diagnostic sensitivity was 98.7% (95% CI
      87.5%-98.6%) and NPV was 99.0% (95% CI 94.3%-100.0%). Of the 17.3% (n = 80)
      patients with hs-cTnT below the LoD and no ECG ischemia, none had AMI. Thus,
      diagnostic sensitivity was 100.0% (95% CI 95.4%-100.0%) and NPV was 100.0% (95%
      CI 95.5%-100.0%). Sensitivity and NPV were maintained when AMI was readjudicated
      on the basis of hs-cTnT. CONCLUSIONS: Our findings confirm that patients with
      nonischemic ECG and undetectable hs-cTnT at presentation have a very low
      probability of AMI, although the proportion of patients affected was smaller than
      in previous research.

PMID- 25979954
TI  - Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in
      estrogen receptor-positive metastatic breast cancer.
AB  - BACKGROUND: Activating mutations in the estrogen receptor 1 (ESR1) gene are
      acquired on treatment and can drive resistance to endocrine therapy. Because of
      the spatial and temporal limitations of needle core biopsies, our goal was to
      develop a highly sensitive, less invasive method of detecting activating ESR1
      mutations via circulating cell-free DNA (cfDNA) and tumor cells as a "liquid
      biopsy." METHODS: We developed a targeted 23-amplicon next-generation sequencing
      (NGS) panel for detection of hot-spot mutations in ESR1, phosphatidylinositol-4,5
      bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tumor protein p53
      (TP53), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor
      receptor 2 (FGFR2) in 48 patients with estrogen receptor-alpha-positive
      metastatic breast cancer who were receiving systemic therapy. Selected mutations
      were validated using droplet digital PCR (ddPCR). RESULTS: Nine baseline cfDNA
      samples had an ESR1 mutation. NGS detected 3 activating mutations in ESR1, and 3
      hot-spot mutations in PIK3CA, and 3 in TP53 in baseline cfDNA, and the ESR1
      p.D538G mutation in 1 matched circulating tumor cell sample. ddPCR analysis was
      more sensitive than NGS and identified 6 additional baseline cfDNA samples with
      the ESR1 p.D538G mutation at a frequency of <1%. In serial blood samples from 11
      patients, 4 showed changes in cfDNA, 2 with emergence of a mutation in ESR1. We
      also detected a low frequency ESR1 mutation (1.3%) in cfDNA of 1 primary patient
      who was thought to have metastatic disease but was clear by scans. CONCLUSIONS:
      Early identification of ESR1 mutations by liquid biopsy might allow for cessation
      of ineffective endocrine therapies and switching to other treatments, without the
      need for tissue biopsy and before the emergence of metastatic disease.

PMID- 25979955
TI  - Can we change a genetically determined future?
AB  - We describe the clinical evolution of the first patient diagnosed with a severe
      alpha-1 antitrypsin (AAT) deficiency caused by a rare null allele (Q0Ourem), over
      the past 18 years. We highlight the clinical course of the disease as well as the
      evolution of the pulmonary function tests from initial diagnosis and the benefits
      of augmentation therapy for this specific condition. We report the case of a 43
      year-old man with exertion dyspnoea who was observed in our pulmonology unit. The
      unexpected findings in the complementary examinations led us to diagnose AAT
      deficiency and to the discovery of a new mutation with the SERPIN A1 gene (hence
      named Q0Ourem) responsible for the disease. Augmentation therapy was initiated,
      as is the protocol in this condition. Eighteen years after the diagnosis, the
      patient is clinically stable, fully autonomous and maintaining an acceptable
      quality of life, despite severe obstructive lung disease.

PMID- 25979956
TI  - Reversible transverse sinus collapse in a patient with idiopathic intracranial
      hypertension.
AB  - The association of idiopathic intracranial hypertension (IIH) with stenosis or
      narrowing of the transverse sinuses (TSs) is well known. However, there is debate
      as to whether the stenosis is a cause or consequence. Here we describe a case of
      IIH and narrowing of the TSs, with four relapses and recoveries after repeated
      CSF diversions with lumbar puncture (LP) over 2 months. Subsequently,
      implantation of a lumboperitoneal shunt (LPrS) ensured recovery. MR venography 20
      months after LPrS showed normally calibrated TSs. We show repeated MR venography
      findings before and after the LPs, and discuss the pathogenesis of IIH in terms
      of the cause and effect relationship between IIH and sinus collapse. 

PMID- 25979957
TI  - Successful use of Rituximab in a patient with recalcitrant multisystemic
      eosinophilic granulomatosis with polyangiitis.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare eosinophil-rich
      disorder characterised by necrotising granulomatous inflammation affecting small
      to medium sized vessels. Extrapulmonary manifestations can be life-threatening
      when heart, central nervous system (CNS), gastrointestinal tract or kidneys are
      affected. We describe a case of a 56-year-old woman with a long-standing history
      of asthma, who presented with an acute sudden painless loss of vision after she
      had been recently diagnosed with EGPA and induced with pulse steroids and
      cyclophosphamide. The patient had a complicated hospital course with
      multisystemic involvement of active vasculitis, involving heart, kidneys,
      muscles, eyes and CNS. The patient's devastating condition responded remarkably
      to Rituximab. The role of Rituximab in EGPA is not yet proven. Few cases are
      reported in the literature about the role of Rituximab in EGPA, of which only one
      described retinal artery occlusion as a presentation of a recently treated
      patient with EGPA. 

PMID- 25979958
TI  - Left-sided transmesocolic herniation of small bowel in an otherwise unaffected
      abdomen.
AB  - Transmesocolic hernia is an uncommon type of internal hernia with incidence
      ranging from approximately 5-10%. To the best of our knowledge, this is the first
      reported case of a transmesocolic hernia through a gap within the descending
      mesocolon presenting clinically as an intestinal obstruction. A 75-year-old man
      was admitted with clinical features of intestinal obstruction. An abdominal X-ray
      showed multiple small bowel loops with air fluid levels. Contrast-enhanced CT of
      the abdomen revealed small bowel obstruction not only on the right, but also on
      the left side of the collapsed descending colon. Emergency surgery was performed.
      Strangulated bowel loops with gangrenous changes were resected and double-barrel
      ileostomy was carried out. The postoperative period was uneventful. Restoration
      of bowel was performed after 6 weeks. Preoperative diagnosis of bowel obstruction
      caused by a transmesocolic hernia remains difficult despite the currently
      available imaging techniques. Prompt surgery can prevent serious complications
      such as peritonitis and sepsis. 

PMID- 25979959
TI  - Simultaneous dislocation of both interphalangeal joints in the middle finger.
AB  - Simultaneous dorsal dislocation of both interphalangeal joints (IPJs) in one
      finger is an uncommon injury. This injury usually occurs on the ulnar side of the
      hand involving ring and little fingers. We report a case of simultaneous
      dislocation of both IPJs in the middle finger. Closed reduction and splinting
      with the IPJs in extension provided a good result with full range of motion at
      the patient's final follow-up. 

PMID- 25979960
TI  - Learning the hard way: when a CT scan misleads your diagnosis.
AB  - Oesophageal injury due to blunt trauma is extremely rare, and when it presents it
      carries a very high mortality. Time is of essence and if not promptly recognised
      these injuries could have devastating consequences. We report a case emphasising
      the importance of oesophagoscopy in diagnosing oesophageal injuries. A young man
      presented to our emergency ward as an unwitnessed road traffic accident after
      receiving first aid from a secondary care facility. At presentation, he was
      haemodynamically stable with decreased power in lower limbs, and with severe neck
      and back pain. There was high suspicion of spinal injury, which was later evident
      on clinical and on radiological findings. A CT scan revealed oesophageal injury,
      indicated by contrast extravasation, which was convincing enough to proceed
      without endoscopy. Surprisingly, the apparently convincing injury picked up on CT
      scan marked by contrast extravasation turned out to be an artefact, which led to
      a negative surgical exploration. 

PMID- 25979962
TI  - Metachronous multicentric giant cell tumour in a young woman.
AB  - Multicentric giant cell tumours (GCTs) are very rare and account for less than 1%
      of all GCTs of bone. We report a case of a young woman with metachronous
      multicentric GCTs with 5 documented lesions in the same lower limb. The initial
      lesion started during the first trimester of pregnancy around her right pelvis,
      which rapidly progressed as a painful swelling with gradually restricted mobility
      of her right hip joint. The radiological appearance of this tumour was that of a
      GCT and biopsy confirmed the diagnosis. The role of positron emission tomography
      (PET) has been highlighted to detect occult lesions. A possible hormonal
      correlation for these tumours has been discussed. The patient was managed
      successfully by an aggressive surgical approach for knee and talar lesions,
      whereas repeated embolisation and denosumab injections were given to treat her
      pelvic lesion. 

PMID- 25979961
TI  - Importance of repeat angiography in the diagnosis of iatrogenic anterior cerebral
      artery territory pseudoaneurysm following endoscopic sinus surgery.
AB  - Iatrogenic intracranial pseudoaneurysm formation and rupture are rare
      complications following endoscopic sinus surgery. Given the propensity for
      devastating neurologic injury after a relatively routine procedure, swift
      diagnosis and treatment is essential. The authors present a patient who
      experienced bifrontal intracranial hemorrhage and subarachnoid hemorrhage due to
      a ruptured iatrogenic frontopolar artery pseudoaneurysm caused during routine
      endoscopic sinus surgery. The pseudoaneurysm was not present on initial
      angiograms but became apparent radiographically 19 days after the endoscopic
      procedure. Endovascular treatment consisted of coil and Onyx embolization for
      sacrifice of the parent vessel proximal to the lesion. Early recognition of
      iatrogenic intracranial vascular injury is important to allow for rapid
      treatment. Initial radiographic studies may be unreliable in excluding the
      presence of a pseudoaneurysm so delayed repeat angiographic assessment is
      necessary, particularly in the presence of a high index of clinical suspicion.
      Endovascular techniques may provide an effective and safe option for the
      treatment of iatrogenic anterior cerebral artery distribution pseudoaneurysms. 

PMID- 25979963
TI  - Non-elevation of TSH after total thyroidectomy: a surgical surprise.
AB  - A 31-year-old woman with papillary carcinoma of the thyroid with right cervical
      lymph nodal metastasis underwent total thyroidectomy with modified radical neck
      dissection. At follow-up 6 weeks after surgery, she had not developed clinical
      features of hypothyroidism and her thyroid-stimulating hormone (TSH) was within
      normal limits. Further evaluation including technetium scintigraphy of the
      thyroid and MRI of the chest confirmed thyroid tissue, thyrothymic thyroid rest
      (TTR), in the superior mediastinum. The patient's TSH elevated well after
      reoperation of TTR. She underwent radioiodine ablative therapy and suppressive
      thyroxine therapy as per the protocol for well-differentiated thyroid cancer
      follow-up. The clinical importance of these embryological rests of thyroid
      tissue, especially in the management of thyroid malignancies, is discussed in
      this report. 

PMID- 25979964
TI  - Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 25979965
TI  - Patterns of genetic diversity in three plant lineages endemic to the Cape Verde
      Islands.
AB  - Conservation of plant diversity on islands relies on a good knowledge of the
      taxonomy, distribution and genetic diversity of species. In recent decades, a
      combination of morphology- and DNA-based approaches has become the standard for
      investigating island plant lineages and this has led, in some cases, to the
      discovery of previously overlooked diversity, including 'cryptic species'. The
      flora of the Cape Verde archipelago in the North Atlantic is currently thought to
      comprise ~740 vascular plant species, 92 of them endemics. Despite the fact that
      it is considered relatively well known, there has been a 12 % increase in the
      number of endemics in the last two decades. Relatively few of the Cape Verde
      plant lineages have been included in genetic studies so far and little is known
      about the patterns of diversification in the archipelago. Here we present an
      updated list for the endemic Cape Verde flora and analyse diversity patterns for
      three endemic plant lineages (Cynanchum, Globularia and Umbilicus) based on one
      nuclear (ITS) and four plastid DNA regions. In all three lineages, we find
      genetic variation. In Cynanchum, we find two distinct haplotypes with no clear
      geographical pattern, possibly reflecting different ploidy levels. In Globularia
      and Umbilicus, differentiation is evident between populations from northern and
      southern islands. Isolation and drift resulting from the small and fragmented
      distributions, coupled with the significant distances separating the northern and
      southern islands, could explain this pattern. Overall, our study suggests that
      the diversity in the endemic vascular flora of Cape Verde is higher than
      previously thought and further work is necessary to characterize the flora. 

PMID- 25979967
TI  - Introduction to the Special Issue: The role of soil microbial-driven belowground
      processes in mediating exotic plant invasions.
AB  - Soil microbial communities are one of the multiple factors that facilitate or
      resist plant invasion. Regional and biogeographic studies help to determine how
      soil communities and the processes mediated by soil microbes are linked to other
      mechanisms of invasion. Both the success of plant invasions and their impacts are
      profoundly influenced by a wide range of soil communities and the soil processes
      mediated by them. With an aim to better understand the mechanisms responsible for
      the soil community-driven routes, a special issue of AoB PLANTS was conceived. I
      hope that the range of papers included in the special issue will reveal some of
      the complexities in soil community-mediated plant invasion. 

PMID- 25979966
TI  - Inter-plant communication through mycorrhizal networks mediates complex adaptive
      behaviour in plant communities.
AB  - Adaptive behaviour of plants, including rapid changes in physiology, gene
      regulation and defence response, can be altered when linked to neighbouring
      plants by a mycorrhizal network (MN). Mechanisms underlying the behavioural
      changes include mycorrhizal fungal colonization by the MN or interplant
      communication via transfer of nutrients, defence signals or allelochemicals. We
      focus this review on our new findings in ectomycorrhizal ecosystems, and also
      review recent advances in arbuscular mycorrhizal systems. We have found that the
      behavioural changes in ectomycorrhizal plants depend on environmental cues, the
      identity of the plant neighbour and the characteristics of the MN. The
      hierarchical integration of this phenomenon with other biological networks at
      broader scales in forest ecosystems, and the consequences we have observed when
      it is interrupted, indicate that underground 'tree talk' is a foundational
      process in the complex adaptive nature of forest ecosystems. 

PMID- 25979968
TI  - Evolving Information Needs among Colon, Breast, and Prostate Cancer Survivors:
      Results from a Longitudinal Mixed-Effects Analysis.
AB  - BACKGROUND: This study describes how cancer survivors' information needs about
      recurrence, late effects, and family risks of cancer evolve over the course of
      their survivorship period. METHODS: Three annual surveys were conducted from 2006
      to 2008 in a cohort of Pennsylvania cancer survivors diagnosed with colon,
      breast, or prostate cancer in 2005 (round 1, N = 2,013; round 2, N = 1,293; round
      3, N = 1,128). Outcomes were information seeking about five survivorship topics.
      Key predictors were survey round, cancer diagnosis, and the interaction between
      these variables. Mixed-effects logistic regression analyses were performed to
      predict information seeking about each topic, adjusting for demographic
      variables, clinical characteristics, and clustering of repeated observations
      within individuals. RESULTS: Information seeking about reducing risks of cancer
      recurrence was the most frequently reported topic across survivors and over time.
      Breast cancer survivors were more likely to seek about survivorship topics at
      round 1 compared with other survivors. In general, information seeking declined
      over time, but cancer-specific patterns emerged: the decline was sharpest for
      breast cancer survivors, whereas in later years female colon cancer survivors
      actually sought more information (about how to reduce the risk of family members
      getting colon cancer or a different cancer). CONCLUSION: Cancer survivors'
      information needs varied over time depending on the topic, and these trends
      differed by cancer type. IMPACT: Clinicians may need to intervene at distinct
      points during the survivorship period with information to address concerns about
      cancer recurrence, late effects, and family members' risks.

PMID- 25979969
TI  - A cell-based screening for TAZ activators identifies ethacridine, a widely used
      antiseptic and abortifacient, as a compound that promotes dephosphorylation of
      TAZ and inhibits adipogenesis in C3H10T1/2 cells.
AB  - Transcriptional co-activator with PSD-95/Dlg-A/ZO-1 (PDZ)-binding motif (TAZ)
      regulates in cell proliferation and differentiation. In mesenchymal stem cells it
      promotes osteogenesis and myogenesis, and suppresses adipogenesis. TAZ activators
      are expected to prevent osteoporosis, obesity and muscle atrophy. TAZ activation
      induces epithelial-mesenchymal transition, confers stemness to cancer cells and
      leads to poor clinical prognosis in cancer patients. In this point of view, TAZ
      inhibitors should contribute to cancer therapy. Thus, TAZ attracts attention as a
      two-faced drug target. We screened for TAZ modulators by using human lung cancer
      A549 cells expressing the fluorescent reporter. Through this assay, we obtained
      TAZ activator candidates. We unexpectedly found that ethacridine, a widely used
      antiseptic and abortifacient, enhances the interaction of TAZ and protein
      phosphatases and increases unphosphorylated and nuclear TAZ. Ethacridine inhibits
      adipogenesis in mesenchymal C3H10T1/2 cells through the activation of TAZ. This
      finding suggests that ethacridine is a bona fide TAZ activator and supports that
      our assay is useful to discover TAZ activators. 

PMID- 25979970
TI  - Low Triiodothyronine Syndrome and Long-Term Cardiovascular Outcome in Incident
      Peritoneal Dialysis Patients.
AB  - BACKGROUND AND OBJECTIVES: A direct association between low triiodothyronine (T3)
      syndrome and cardiovascular (CV) mortality has been reported in hemodialysis
      patients. However, the implications of this syndrome in peritoneal dialysis (PD)
      patients have not been properly investigated. This study examined the association
      between low T3 syndrome and CV mortality including sudden death in a large cohort
      of incident PD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      prospective observational study included 447 euthyroid patients who started PD
      between January 2000 and December 2009. Measurement of thyroid hormones was
      performed at baseline. All-cause and cause-specific deaths were registered during
      the median 46 months of follow-up. The survival rate was compared among three
      groups based on tertile of T3 levels. RESULTS: In Kaplan-Meyer analysis, patients
      with the lowest tertile were significantly associated with higher risk of all
      cause and CV mortality including sudden death (P<0.001 for trend). In Cox
      analyses, T3 level was a significant predictor of all-cause mortality (per 10
      unit increase, adjusted hazard ratio [HR], 0.86; 95% confidence interval [95%
      CI], 0.78 to 0.94; P=0.002), CV death (per 10-unit increase, adjusted HR, 0.84;
      95% CI, 0.75 to 0.98; P=0.01), and sudden death (per 10-unit increase, adjusted
      HR, 0.69; 95% CI, 0.56 to 0.86; P=0.001) after adjusting for well known risk
      factors including inflammation and malnutrition. The higher T3 level was also
      independently associated with lower risk for sudden death (per 10-unit increase,
      adjusted HR, 0.71; 95% CI, 0.56 to 0.90; P=0.01) even when accounting for
      competing risks of death from other causes. CONCLUSIONS: T3 level at the
      initiation of PD was a strong independent predictor of long-term CV mortality,
      particularly sudden death, even after adjusting well known risk factors. Low T3
      syndrome might represent a factor directly implicated in cardiac complications in
      PD patients.

PMID- 25979972
TI  - BP Components in Advanced CKD and the Competing Risks of Death, ESRD, and
      Cardiovascular Events.

PMID- 25979971
TI  - Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and
      Mycophenolate With or Without Steroid Maintenance.
AB  - BACKGROUND AND OBJECTIVES: Induction therapy with IL-2 receptor antagonist (IL2
      RA) is recommended as a first line agent in living donor renal transplantation
      (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus
      (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The Organ Procurement and Transplantation Network
      registry was studied for patients receiving LRT from 2000 to 2012 maintained on
      TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other
      induction options. The cohort was initially divided into two groups based on use
      of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus
      no-steroid (n=10,157). Each group was further stratified into three categories
      according to commonly used antibody induction approach: IL2-RA, rabbit anti
      thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA,
      r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of
      acute rejection at 1 year and overall allograft failure (graft failure or death)
      post-transplantation through the end of follow-up. Propensity score-weighted
      regression analysis was used to minimize selection bias due to non-random
      assignment of induction therapies. RESULTS: Multivariable logistic and Cox
      analysis adjusted for propensity score showed that outcomes in the steroid group
      were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval
      [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI,
      0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no
      steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to
      0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however,
      overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI,
      1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with
      IL2-RA induction. CONCLUSIONS: Compared with no-induction therapy, IL2-RA
      induction was not associated with better outcomes when TAC/MPA/steroids were used
      in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred
      induction alternative for IL2-RA in steroid-avoidance protocols.

PMID- 25979973
TI  - Low-T3 Syndrome in Peritoneal Dialysis: Metabolic Adaptation, Marker of Illness,
      or Mortality Mediator?

PMID- 25979974
TI  - Should Hemoglobin A1C Be Routinely Measured in Patients with CKD?

PMID- 25979976
TI  - What Medical Directors Need to Know about Dialysis Facility Water Management.
AB  - The medical directors of dialysis facilities have many operational clinic
      responsibilities, which on first glance, may seem outside the realm of excellence
      in patient care. However, a smoothly running clinic is integral to positive
      patient outcomes. Of the conditions for coverage outlined by the Centers for
      Medicare and Medicaid Services, one most critical to quality dialysis treatment
      is the provision of safe purified dialysis water, because there are many
      published instances where clinic failure in this regard has resulted in patient
      harm. As the clinical leader of the facility, the medical director is obliged to
      have knowledge of his/her facility's water treatment system to reliably ensure
      that the purified water used in dialysis will meet the standards for quality set
      by the Association for the Advancement of Medical Instrumentation and used by the
      Centers for Medicare and Medicaid Services for conditions for coverage. The
      methods used to both achieve and maintain these quality standards should be a
      part of quality assessment and performance improvement program meetings. The
      steps for water treatment, which include pretreatment, purification, and
      distribution, are largely the same, regardless of the system used. Each water
      treatment system component has a specific role in the process and requires
      individualized maintenance and monitoring. The medical director should provide
      leadership by being engaged with the process, knowing the facility's source
      water, and understanding water treatment system operation as well as the clinical
      significance of system failure. Successful provision of quality water will be
      achieved by those medical directors who learn, know, and embrace the requirements
      of dialysis water purification and system maintenance. 

PMID- 25979975
TI  - Association of BP with Death, Cardiovascular Events, and Progression to Chronic
      Dialysis in Patients with Advanced Kidney Disease.
AB  - BACKGROUND AND OBJECTIVE: The optimal BP target to reduce adverse clinical
      outcomes in patients with CKD is unclear. This study examined the relationship
      between BP and death, cardiovascular events (CVEs), and kidney disease
      progression in patients with advanced kidney disease. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The relationship of systolic BP (SBP), diastolic BP
      (DBP), and pulse pressure (PP) with death, CVE, and progression to long-term
      dialysis was examined in 1099 patients with advanced CKD (eGFR<=30 ml/min per 1.7
      3m(2); not receiving dialysis) who participated in the Homocysteine in Kidney and
      ESRD study. That study enrolled participants from 2001 to 2003. Cox proportional
      hazard models were used to examine the association between BP and adverse
      outcomes. RESULTS: The mean+/-SD baseline eGFR was 18+/-7 ml/min per 1.73 m(2).
      During a median follow-up of 2.9 years, 453 patients died, 215 had a CVE, and 615
      initiated long-term dialysis. After adjustment for demographic characteristics
      and confounders, SBP, DBP, and PP were not associated with a higher risk of
      death. SBP and DBP were also not associated with CVE. The highest quartile of PP
      was associated with a substantial higher risk of CVE compared with the lowest
      quartile (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.10 to
      2.52). The highest quartiles of SBP (HR, 1.28; 95% CI, 1.01 to 1.61) and DBP (HR,
      1.36; 95% CI, 1.07 to 1.73), but not PP, were associated with a higher risk of
      progression to long-term dialysis compared with the lowest quartile. CONCLUSIONS:
      In patients with advanced kidney disease not undergoing dialysis, higher PP was
      strongly associated with CVE whereas higher SBP and DBP were associated with
      progression to long-term dialysis. These results suggest that SBP and DBP should
      not be the only factors considered in determining antihypertensive therapy;
      elevated PP should also be considered.

PMID- 25979977
TI  - Induction Therapy in Renal Transplantation: Why? What Agent? What Dose? We May
      Never Know.

PMID- 25979980
TI  - Tribute to Alan Hall.

PMID- 25979978
TI  - Glycated Hemoglobin Level and Mortality in a Nondiabetic Population with CKD.
AB  - BACKGROUND AND OBJECTIVES: Glycated hemoglobin (HbA1c) is used to diagnose
      diabetes mellitus (DM) and guide its management. The association between higher
      HbA1c and progression to ESRD and mortality has been demonstrated in populations
      with DM. This study examined the association between HbA1c and these end points
      in a population with CKD and without DM. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In the hospital-based NephroTest cohort study, measured GFR (mGFR)
      was taken by (51)Cr-EDTA renal clearance and HbA1c in 1165 adults with
      nondialysis CKD stages 1-5 and without DM between January 2000 and December 2010.
      The median follow-up was 3.48 years (interquartile range, 1.94-5.82) for the
      competing events of ESRD and pre-ESRD mortality. Time-fixed and time-dependent
      Cox models were used to estimate hazard ratios (HRs) for ESRD and mortality
      according to HbA1c, treated continuously or in tertiles. RESULTS: At inclusion,
      the mean mGFR was 42.2+/-19.9 ml/min per 1.73 m(2), and the mean HbA1c value was
      5.5%+/-0.5%. During follow-up, 109 patients died, and 162 patients reached ESRD.
      Pre-ESRD mortality was significantly associated with HbA1c treated continuously:
      for every 1% higher HbA1c, the crude HR was 2.16 (95% confidence interval [95%
      CI], 1.27 to 3.68), and it was 1.85 (95% CI, 1.05 to 3.24) after adjustment for
      mGFR and other risk factors of death. After excluding incident diabetes over
      time, the updated mean of HbA1c remained significantly associated with higher
      mortality risk: adjusted HR for the highest (5.7%-6.4%) versus the lowest tertile
      (<5.3%) was 2.62 (95% CI, 1.16 to 5.91). There was no association with ESRD risk
      after adjustment for risk factors of CKD progression. CONCLUSIONS: In a CKD
      cohort, HbA1c values in the prediabetes range are associated with mortality. Such
      values should be therefore included among the risk factors for negative outcomes
      in CKD populations.

PMID- 25979979
TI  - DroughtDB: an expert-curated compilation of plant drought stress genes and their
      homologs in nine species.
AB  - Plants are sessile and therefore exposed to a number of biotic and abiotic
      stresses. Drought is the major abiotic stress restricting plant growth worldwide.
      A number of genes involved in drought stress response have already been
      characterized, mainly in the model species Arabidopsis thaliana and Oryza sativa.
      However, with the aim to produce drought tolerant crop varieties, it is of
      importance to identify the respective orthologs for each species. We have
      developed DroughtDB, a manually curated compilation of molecularly characterized
      genes that are involved in drought stress response. DroughtDB includes
      information about the originally identified gene, its physiological and/or
      molecular function and mutant phenotypes and provides detailed information about
      computed orthologous genes in nine model and crop plant species including maize
      and barley. All identified orthologs are interlinked with the respective
      reference entry in MIPS/PGSB PlantsDB, which allows retrieval of additional
      information like genome context and sequence information. Thus, DroughtDB is a
      valuable resource and information tool for researchers working on drought stress
      and will facilitate the identification, analysis and characterization of genes
      involved in drought stress tolerance in agriculturally important crop plants.
      Database URL: http://pgsb.helmholtz-muenchen.de/droughtdb/

PMID- 25979981
TI  - From RAS to RHO: The making of the great cell biologist Alan Hall (1952-2015).

PMID- 25979982
TI  - Effects of Morphographic Instruction on the Morphographic Analysis Skills of Deaf
      and Hard-of-Hearing Students.
AB  - Deaf and hard-of-hearing (DHH) students have delayed morphographic knowledge that
      negatively affects their morphographic analysis and decoding abilities.
      Morphographic analysis instruction may improve DHH students' morphographic
      knowledge delay. The purpose of this study was to determine the effects of
      morphographic instruction on the morphographic analysis skills of reading
      delayed, late-elementary DHH students. The research question was: What effect
      does morphographic instruction have on the morphographic analysis skills of DHH
      students who are reading below grade level? The study included 3 student
      participants and 1 teacher participant from a local school district. The
      researchers used a multiprobe multiple baseline across participants design. The
      intervention was implemented for 20 min a day, 5 days a week for 2-3 weeks.
      Visual analysis of the data revealed the requisite number of demonstrations of
      effect and replications. The intervention improved DHH students' ability to
      dissect words and determine affix meanings, which may in turn positively affect
      their decoding abilities. Implications of this study and future research are
      discussed.

PMID- 25979983
TI  - Correction for Doores et al., Two Classes of Broadly Neutralizing Antibodies
      within a Single Lineage Directed to the High-Mannose Patch of HIV Envelope.

PMID- 25979984
TI  - Correction for Ingale et al., Hyperglycosylated stable core immunogens designed
      to present the CD4 binding site are preferentially recognized by broadly
      neutralizing antibodies.

PMID- 25979986
TI  - Overview of contemporary guidelines in digital pathology: what is available in
      2015 and what still needs to be addressed?
AB  - As technological advancements continue to transform the practice of pathology,
      new adopters of these technologies will look to guidelines on how best to
      incorporate them with an eye to preserving and enhancing patient safety and
      diagnostic quality. Telepathology, using a variety of digital pathology
      modalities, has tremendous potential to achieve that goal. Pathology departments
      are increasingly looking to implement different digital pathology platforms,
      whole slide imaging (WSI) systems in particular, for a broad range of
      applications in patient care. WSI allows for the acquisition, management and
      review of completely digitised slides as would be done with a light microscope.
      WSI also facilitates image analysis that cannot be carried out by a pathologist
      using traditional microscopy. Over the last few years, the Digital Pathology
      Association, The Royal College of Pathologists, College of American Pathologists,
      Canadian Association of Pathologists, the American Telemedicine Association and
      the Society of Toxicologic Pathology have published guidelines for validating and
      implementing digital pathology systems. This review summarises, compares and
      contrasts these published guidelines and discusses pertinent issues that need to
      be addressed as the guidelines are revised in the future. 

PMID- 25979987
TI  - Heterozygous bone marrow in a homozygous mature ovarian teratoma: a challenge to
      the germ cell theory or incidental somatic heterotopia?

PMID- 25979988
TI  - Measurement of nucleated red blood cells in the peripheral blood as a marker of
      hypoxia in sudden unexpected death in infancy.
AB  - AIMS: A recently proposed classification of sudden unexpected infant death
      incorporates consideration of possibly asphyxia. This depends on an adequate
      postmortem, scene investigation and history. A reliable marker of asphyxia has
      yet to be identified. Such a marker could assist in classifying these deaths. Our
      aim was to determine if the level of nucleated red blood cells (nRBCs) in the
      peripheral blood could help identify those possibly asphyxia-related deaths and
      if risk factors could influence this level in the peripheral blood. METHODS:
      Cases of sudden unexpected deaths in infancy and sudden infant death syndrome
      (SIDS) which occurred over a period of 6 years (2007-2013) and were autopsied at
      Sheffield Children's Hospital were reviewed and categorised according to a new
      classification proposed by Randall et al. The cases were then correlated with the
      blood level of nRBCs determined at the time of post mortem examination. The study
      was approved by the Clinical Governance Department, number SE331. RESULTS: 139
      deaths were classified into Group A (true SIDS, 67 cases), Group B (possible
      asphyxia related, 24 cases), Group C (non-asphyxia-related, 6 cases), Group D (no
      crime scene investigation, 0 cases) and Group E (identifiable cause, 42 cases).
      The levels were significantly increased in ex-premature babies, in infants with
      an underlying condition (Group C) and in deaths related to illness or trauma
      (Group E). There was a trend towards higher levels of nRBCs in younger age groups
      and in babies born to smoking mothers. CONCLUSIONS: SIDS remains a difficult
      diagnosis to make despite the current medical technological advances where no
      marker of hypoxia has yet been identified.

PMID- 25979989
TI  - Human gammaherpesviruses viraemia in HIV infected patients.
AB  - BACKGROUND: The Epstein-Barr virus (EBV) and Kaposi's sarcoma associated
      herpesvirus (KSHV) are consistently associated with lymphoproliferative diseases
      and cancers in humans, notably in patients with HIV. AIMS: Our aim was to
      evaluate whether EBV and/or KSHV viral loads regularly assessed in peripheral
      blood mononuclear cells (PBMC) correlate with clinical or laboratorial parameters
      retrieved for patients living with HIV. METHODS: This was a longitudinal study
      with a cohort of 157 HIV positive patients attending an academic HIV outpatient
      clinic in Sao Paulo State, Brazil. For each patient, up to four blood samples
      were collected over a 1 year clinical follow-up: on enrolment into the study, and
      after 4, 8 and 12 months. Total DNA was extracted from PBMC, and EBV and KSHV
      viral loads were assessed by real time quantitative PCR. RESULTS: Higher viral
      loads for EBV were significantly associated with high HIV viraemia, a greater
      number of circulating T CD8+ cells and lack of virological response to the
      antiretroviral treatment. KSHV viral load was undetectable in virtually all
      samples. CONCLUSIONS: EBV viral load in PBMC correlated with the number of
      circulating T CD8+ lymphocytes and the response to the antiretroviral therapy in
      HIV infected patients. In contrast, KSHV was undetectable in PBMC, presumably an
      effect of the antiretroviral treatment. Therefore, either KSHV infection in the
      population studied was absent or viral load in PBMC was beyond the analytical
      limit of the assay.

PMID- 25979990
TI  - The prelimbic cortex directs attention toward predictive cues during fear
      learning.
AB  - The prelimbic cortex is argued to promote conditioned fear expression, at odds
      with appetitive research implicating this region in attentional processing.
      Consistent with an attentional account, we report that the effect of prelimbic
      lesions on fear expression depends on the degree of competition between
      contextual and discrete cues. Further, when competition from contextual cues is
      low, we found that PL inactivation resulted in animals expressing fear toward
      irrelevant discrete cues; an effect selective to inactivation during the learning
      phase and not during retrieval. These data demonstrate that the prelimbic cortex
      modulates attention toward cues to preferentially direct fear responding on the
      basis of their predictive value. 

PMID- 25979991
TI  - Outcome learning, outcome expectations, and intentionality in Drosophila.
AB  - An animal generates behavioral actions because of the effects of these actions in
      the future. Occasionally, the animal may generate an action in response to a
      certain event or situation. If the outcome of the action is adaptive, the animal
      may keep this stimulus-response link in its behavioral repertoire, in case the
      event or situation occurs again. If a responsive action is innate but the outcome
      happens to be less adaptive than it had been before, the link may be loosened.
      This adjustment of outcome expectations involves a particular kind of learning,
      which will be called "outcome learning." The present article discusses several
      examples of outcome learning in Drosophila. Learning and memory are intensely
      studied in flies, but the focus is on classical conditioning. Outcome learning, a
      particular form of operant learning, is of special significance, because it
      modulates outcome expectations that are operational components of action
      selection and intentionality. 

PMID- 25979992
TI  - Frontal neurons modulate memory retrieval across widely varying temporal scales.
AB  - Once a memory has formed, it is thought to undergo a gradual transition within
      the brain from short- to long-term storage. This putative process, however, also
      poses a unique problem to the memory system in that the same learned items must
      also be retrieved across broadly varying time scales. Here, we find that neurons
      in the ventrolateral prefrontal cortex (VLPFC) of monkeys, an area interconnected
      with both temporal and frontal associative neocortical regions, signaled the need
      to alter between retrieval of memories formed at different times. These signals
      were most closely related to the time interval between initial learning and later
      retrieval, and did not correlate with task switch demands, novelty, or behavioral
      response. Consistent with these physiological findings, focal inactivation of the
      VLPFC led to a marked degradation in retrieval performance. These findings
      suggest that the VLPFC plays a necessary regulatory role in retrieving memories
      over different temporal scales. 

PMID- 25979993
TI  - Phase matters: responding to and learning about peripheral stimuli depends on
      hippocampal theta phase at stimulus onset.
AB  - Hippocampal theta (3-12 Hz) oscillations are implicated in learning and memory,
      but their functional role remains unclear. We studied the effect of the phase of
      local theta oscillation on hippocampal responses to a neutral conditioned
      stimulus (CS) and subsequent learning of classical trace eyeblink conditioning in
      adult rabbits. High-amplitude, regular hippocampal theta-band responses (that
      predict good learning) were elicited by the CS when it was timed to commence at
      the fissure theta trough (Trough group). Regardless, learning in this group was
      not enhanced compared with a yoked control group, possibly due to a ceiling
      effect. However, when the CS was consistently presented to the peak of theta
      (Peak group), hippocampal theta-band responding was less organized and learning
      was retarded. In well-trained animals, the hippocampal theta phase at CS onset no
      longer affected performance of the learned response, suggesting a time-limited
      role for hippocampal processing in learning. To our knowledge, this is the first
      study to demonstrate that timing a peripheral stimulus to a specific phase of the
      hippocampal theta cycle produces robust effects on the synchronization of neural
      responses and affects learning at the behavioral level. Our results support the
      notion that the phase of spontaneous hippocampal theta oscillation is a means of
      regulating the processing of information in the brain to a behaviorally relevant
      degree. 

PMID- 25979995
TI  - Amylopectin biosynthetic enzymes from developing rice seed form enzymatically
      active protein complexes.
AB  - Amylopectin is a highly branched, organized cluster of glucose polymers, and the
      major component of rice starch. Synthesis of amylopectin requires fine co
      ordination between elongation of glucose polymers by soluble starch synthases
      (SSs), generation of branches by branching enzymes (BEs), and removal of
      misplaced branches by debranching enzymes (DBEs). Among the various isozymes
      having a role in amylopectin biosynthesis, limited numbers of SS and BE isozymes
      have been demonstrated to interact via protein-protein interactions in maize and
      wheat amyloplasts. This study investigated whether protein-protein interactions
      are also found in rice endosperm, as well as exploring differences between
      species. Gel permeation chromatography of developing rice endosperm extracts
      revealed that all 10 starch biosynthetic enzymes analysed were present at larger
      molecular weights than their respective monomeric sizes. SSIIa, SSIIIa, SSIVb,
      BEI, BEIIb, and PUL co-eluted at mass sizes >700kDa, and SSI, SSIIa, BEIIb, ISA1,
      PUL, and Pho1 co-eluted at 200-400kDa. Zymogram analyses showed that SSI, SSIIIa,
      BEI, BEIIa, BEIIb, ISA1, PUL, and Pho1 eluted in high molecular weight fractions
      were active. Comprehensive co-immunoprecipitation analyses revealed associations
      of SSs-BEs, and, among BE isozymes, BEIIa-Pho1, and pullulanase-type DBE-BEI
      interactions. Blue-native-PAGE zymogram analyses confirmed the glucan
      synthesizing activity of protein complexes. These results suggest that some rice
      starch biosynthetic isozymes are physically associated with each other and form
      active protein complexes. Detailed analyses of these complexes will shed light on
      the mechanisms controlling the unique branch and cluster structure of
      amylopectin, and the physicochemical properties of starch. 

PMID- 25979994
TI  - Biochemical Large-Scale Interaction Analysis of Murine Olfactory Receptors and
      Associated Signaling Proteins with Post-Synaptic Density 95, Drosophila Discs
      Large, Zona-Occludens 1 (PDZ) Domains.
AB  - G protein-coupled receptors (GPCRs) constitute the largest family among mammalian
      membrane proteins and are capable of initiating numerous essential signaling
      cascades. Various GPCR-mediated pathways are organized into protein microdomains
      that can be orchestrated and regulated through scaffolding proteins, such as PSD
      95/discs-large/ZO1 (PDZ) domain proteins. However, detailed binding
      characteristics of PDZ-GPCR interactions remain elusive because these
      interactions seem to be more complex than previously thought. To address this
      issue, we analyzed binding modalities using our established model system. This
      system includes the 13 individual PDZ domains of the multiple PDZ domain protein
      1 (MUPP1; the largest PDZ protein), a broad range of murine olfactory receptors
      (a multifaceted gene cluster within the family of GPCRs), and associated
      olfactory signaling proteins. These proteins were analyzed in a large-scale
      peptide microarray approach and continuative interaction studies. As a result, we
      demonstrate that canonical binding motifs were not overrepresented among the
      interaction partners of MUPP1. Furthermore, C-terminal phosphorylation and
      distinct amino acid replacements abolished PDZ binding promiscuity. In addition
      to the described in vitro experiments, we identified new interaction partners
      within the murine olfactory epithelium using pull-down-based interactomics and
      could verify the partners through co-immunoprecipitation. In summary, the present
      study provides important insight into the complexity of the binding
      characteristics of PDZ-GPCR interactions based on olfactory signaling proteins,
      which could identify novel clinical targets for GPCR-associated diseases in the
      future. 

PMID- 25979996
TI  - Identification of candidate flavonoid pathway genes using transcriptome
      correlation network analysis in ripe strawberry (Fragaria * ananassa) fruits.
AB  - New modulators of the strawberry flavonoid pathway were identified through
      correlation network analysis. The transcriptomes of red, ripe fruit from two
      parental lines and 14 of their progeny were compared, and uncharacterized
      transcripts matching the expression patterns of known flavonoid-pathway genes
      were identified. Fifteen transcripts corresponded with putative transcription
      factors, and several of these were examined experimentally using transient
      expression in developing fruits. The results suggest that two of the newly
      identified regulators likely contribute to discrete nodes of the flavonoid
      pathway. One increases only LEUCOANTHOCYANIDIN REDUCTASE (LAR) and FLAVONOL 3'
      HYDROXYLASE (F3'H) transcript accumulation upon overexpression. Another affects
      LAR and FLAVONOL SYNTHASE (FLS) after overexpression. The third putative
      transcription factor appears to be a universal regulator of flavonoid-pathway
      genes, as many pathway transcripts decrease in abundance when this gene is
      silenced. This report demonstrates that such systems-level approaches may be
      especially powerful when connected to an effective transient expression system,
      helping to provide rapid and strong evidence of gene function in key fruit
      ripening processes. 

PMID- 25979997
TI  - Cytokinin-dependent secondary growth determines root biomass in radish (Raphanus
      sativus L.).
AB  - The root serves as an essential organ in plant growth by taking up nutrients and
      water from the soil and supporting the rest of the plant body. Some plant species
      utilize roots as storage organs. Sweet potatoes (Ipomoea batatas), cassava
      (Manihot esculenta), and radish (Raphanus sativus), for example, are important
      root crops. However, how their root growth is regulated remains unknown. In this
      study, we characterized the relationship between cambium and radial root growth
      in radish. Through a comparative analysis with Arabidopsis root expression data,
      we identified putative cambium-enriched transcription factors in radish and
      analysed their expression in representative inbred lines featuring distinctive
      radial growth. We found that cell proliferation activities in the cambium
      positively correlated with radial growth and final yields of radish roots.
      Expression analysis of candidate transcription factor genes revealed that some
      genes are differentially expressed between inbred lines and that the difference
      is due to the distinct cytokinin response. Taken together, we have demonstrated
      for the first time, to the best of our knowledge, that cytokinin-dependent radial
      growth plays a key role in the yields of root crops. 

PMID- 25979998
TI  - Stem xylem resistance to cavitation is related to xylem structure but not to
      growth and water-use efficiency at the within-population level in Populus nigra
      L.
AB  - Xylem resistance to drought-induced cavitation is a key trait of plant water
      relations. This study assesses the genetic variation expressed for stem
      cavitation resistance within a population of a riparian species, the European
      black poplar (Populus nigra L.), and explores its relationships with xylem
      anatomy, water-use efficiency (WUE), and growth. Sixteen structural and
      physiological traits related to cavitation resistance, xylem anatomy, growth, bud
      phenology, and WUE were measured on 33 P. nigra genotypes grown under optimal
      irrigation in a 2-year-old clonal experiment in a nursery. Significant genetic
      variation was expressed for the xylem tension inducing 50% loss of hydraulic
      conductivity (Psi50) within the studied population, as attested by the high value
      of broad-sense heritability estimated for this trait (H (2) ind = 0.72). Stem
      cavitation resistance was associated with xylem structure: the more cavitation
      resistant genotypes exhibited lower hydraulic efficiency and higher mechanical
      reinforcement as assessed from stem xylem cross sections. By contrast, Psi50 was
      not significantly related to shoot height increment, total above-ground dry mass,
      or bulk leaf carbon isotope discrimination, a proxy for intrinsic WUE. These
      findings indicate that the trade-offs between xylem resistance to cavitation,
      hydraulic efficiency, and mechanical reinforcement can occur at the within
      population level. Given that the studied genotypes were exposed to the same
      environmental conditions and evolutionary drivers in situ, the trade-offs
      detected at this scale are expected to reflect true functional relationships. 

PMID- 25979999
TI  - Functional and expression analyses of kiwifruit SOC1-like genes suggest that they
      may not have a role in the transition to flowering but may affect the duration of
      dormancy.
AB  - The MADS-domain transcription factor SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1
      (SOC1) is one of the key integrators of endogenous and environmental signals that
      promote flowering in the annual species Arabidopsis thaliana. In the deciduous
      woody perennial vine kiwifruit (Actinidia spp.), environmental signals are
      integrated to regulate annual cycles of growth and dormancy. Accumulation of
      chilling during winter is required for dormancy break and flowering in spring. In
      order to understand the regulation of dormancy and flowering in kiwifruit, nine
      kiwifruit SOC1-like genes were identified and characterized. All genes affected
      flowering time of A. thaliana Col-0 and were able to rescue the late flowering
      phenotype of the soc1-2 mutant when ectopically expressed. A differential
      capacity for homodimerization was observed, but all proteins were capable of
      strong interactions with SHORT VEGETATIVE PHASE (SVP) MADS-domain proteins.
      Largely overlapping spatial domains but distinct expression profiles in buds were
      identified between the SOC1-like gene family members. Ectopic expression of
      AcSOC1e, AcSOC1i, and AcSOC1f in Actinidia chinensis had no impact on
      establishment of winter dormancy and failed to induce precocious flowering, but
      AcSOC1i reduced the duration of dormancy in the absence of winter chilling. These
      findings add to our understanding of the SOC1-like gene family and the potential
      diversification of SOC1 function in woody perennials. 

PMID- 25980000
TI  - Antibody testing in aspergillosis--quo vadis?
AB  - Humans are constantly exposed to airborne Aspergillus spores. Most develop
      Aspergillus-specific antibodies by adulthood. Persons with chronic lung disease
      or Aspergillus airway colonization often have raised levels of Aspergillus
      specific immunoglobululin G (IgG). It is not known whether this signifies an
      increased risk of future aspergillosis.Chronic and allergic forms of pulmonary
      aspergillosis are estimated to affect over three million people worldwide.
      Antibody testing is central to diagnosis of these conditions, with raised
      Aspergillus-specific IgG in chronic pulmonary aspergillosis and raised
      Aspergillus-specific IgE in allergic aspergillosis. Antibody levels are also used
      to monitor treatment response in these syndromes. Acute invasive disease is less
      common. There is a more limited role for antibody testing in this setting as
      immunosuppression often results in delayed or absent antibody response.Many
      methods exist to detect Aspergillus-specific antibodies, but there are limited
      published data regarding comparative efficacy and reproducibility. We discuss the
      comparative merits of the available tests in the various clinical settings and
      their suitability for use in the resource-poor settings where the majority of
      cases of aspergillosis are thought to occur. We summarize the gaps in existing
      knowledge and opportunities for further study that could allow optimal use of
      antibody testing in this field. 

PMID- 25980001
TI  - Study on the comparative activity of echinocandins on murine gut colonization by
      Candida albicans.
AB  - Colonization of the gastrointestinal (GI) tract by Candida species is a principal
      pathogenetic event for development of invasive candidiasis. Importantly, the
      effect of echinocandins, the preferred antifungal agents for treatment of
      invasive candidiasis, on GI tract colonization by Candida spp. is currently
      unknown. Herein, we used an established model of persistent murine GI tract
      colonization by Candida albicans to test the ability of different echinocandins
      to eradicate the yeast from murine gut. Adult male Crl:CD1 (ICR) BR mice were fed
      with chow containing C. albicans and subsequently treated with different
      echinocandins or normal saline via daily intraperitoneal injections for 10 days.
      Quantitative stool cultures were performed immediately before (week one), and
      weekly for three months after discontinuation of treatment. Notably, treatment
      with all three echinocandins used (caspofungin, anidulafungin, and micafungin)
      resulted in eradication of Candida albicans from the stools, as evidenced by the
      significant reduction of yeast cells from a mean of 4.2 log10 CFU/g of stool
      before treatment (week one of colonization) to undetectable (<2 log10 CFU/g of
      stool) levels (week 12, P < 0.0001). In contrast, there was no significant
      reduction of Candida yeast cells in the stools of control mice. Collectively, the
      ability of echinocandins to eradicate C. albicans from the stools could have
      important implications in prophylaxis of high-risk patients for development of
      invasive candidiasis originating from the GI tract. 

PMID- 25980002
TI  - Diagnosis of filamentous fungi on tissue sections by immunohistochemistry using
      anti-aspergillus antibody.
AB  - Identification based on histology alone has limitations as Aspergillus species
      share morphology with other filamentous fungi. Differentiation of Aspergillus
      species from hyalohyphomycetes and dematiaceous fungi is important as the
      antifungal susceptibility varies among different species and genera. Given these
      problems, ancillary techniques are needed to increase specificity. Our aim was to
      study the utility of immunohistochemistry (IHC) with anti-Aspergillus antibody in
      the identification of Aspergillus species and to differentiate them from other
      filamentous fungi. Fifty formalin fixed, paraffin embedded tissue sections
      including 47 from cases of culture proven filamentous fungi, 3 from colonies of
      cultures of hyalohyphomycetes, and 11 smears from cultures were subjected to IHC
      studies using polyclonal rabbit anti-Aspergillus antibody (Abcam, UK) after
      antigen retrieval. The IHC on tissue sections was positive in 88% cases involving
      culture proven Aspergillus species. There was no cross reactivity with Mucorales
      species, Candida species, dematiaceous fungi and hyalohyphomycetes. Hence
      immunohistochemistry can be used as an ancillary technique for the diagnosis of
      Aspergillus species. 

PMID- 25980003
TI  - Genotyping, extracellular compounds, and antifungal susceptibility testing of
      Trichosporon asahii isolated from Mexican patients.
AB  - Trichosporon asahii is considered an opportunistic pathogen responsible for
      severe infections, mainly in immunocompromised patients. The aims of this study
      were to investigate the prevalent genotypes among 39 clinical isolates of this
      microorganism by sequencing the IGS1 region and to determine the in vitro
      production of DNAse, hemolysin, aspartyl proteinase, phospholipase and esterase,
      as well as the susceptibilities of the isolates to amphotericin B, anidulafungin,
      micafungin, caspofungin, voriconazole, posaconazole, fluconazole and 5
      flucytosine. Our findings showed that genotype I was the most prevalent
      comprising 69.23% of the isolates. We confirmed the production of esterase for
      all our isolates, and report the production of DNAse and aspartyl proteinase in
      84.62% and 23% of the isolates, respectively. Only one isolate of T. asahii
      produced hemolysin. None of the isolates showed phospholipase activity. Fifty
      three percent of the T. asahii strains exhibited amphotericin B MICs >= 2 MUg/ml.
      The three echinocandins evaluated yielded high MICs (>=2 MUg/ml) in all isolates.
      Thirty-five percent of the isolates had high MICs for 5-flucytosine (>=32
      MUg/ml), and 97% of the isolates were susceptible to the evaluated triazoles. 

PMID- 25980004
TI  - Experimental efficacy of anidulafungin against Aspergillus terreus species
      complex.
AB  - Whereas echinocandins are alternatives for the treatment of invasive
      aspergillosis, the efficacy of anidulafungin (AFG) against Aspergillus terreus
      infection has not yet been explored. We have evaluated the in vitro activity, as
      well as the in vivo efficacy of AFG in neutropenic mice infected by A. terreus
      species complex. Time-kill studies showed in vitro fungistatic activity of AFG
      against two strains. AFG at doses of 5 and 10 mg/kg/day significantly reduced the
      fungal load in kidney of mice, but only the higher dose was able to prolong
      survival. 

PMID- 25980005
TI  - Molecular Evolution of Freshwater Snails with Contrasting Mating Systems.
AB  - Because mating systems affect population genetics and ecology, they are expected
      to impact the molecular evolution of species. Self-fertilizing species experience
      reduced effective population size, recombination rates, and heterozygosity, which
      in turn should decrease the efficacy of natural selection, both adaptive and
      purifying, and the strength of meiotic drive processes such as GC-biased gene
      conversion. The empirical evidence is only partly congruent with these
      predictions, depending on the analyzed species, some, but not all, of the
      expected effects have been observed. One possible reason is that self
      fertilization is an evolutionary dead-end, so that most current selfers recently
      evolved self-fertilization, and their genome has not yet been strongly impacted
      by selfing. Here, we investigate the molecular evolution of two groups of
      freshwater snails in which mating systems have likely been stable for several
      millions of years. Analyzing coding sequence polymorphism, divergence, and
      expression levels, we report a strongly reduced genetic diversity, decreased
      efficacy of purifying selection, slower rate of adaptive evolution, and weakened
      codon usage bias/GC-biased gene conversion in the selfer Galba compared with the
      outcrosser Physa, in full agreement with theoretical expectations. Our results
      demonstrate that self-fertilization, when effective in the long run, is a major
      driver of population genomic and molecular evolutionary processes. Despite the
      genomic effects of selfing, Galba truncatula seems to escape the demographic
      consequences of the genetic load. We suggest that the particular ecology of the
      species may buffer the negative consequences of selfing, shedding new light on
      the dead-end hypothesis. 

PMID- 25980006
TI  - TLR2 stimulation regulates the balance between regulatory T cell and Th17
      function: a novel mechanism of reduced regulatory T cell function in multiple
      sclerosis.
AB  - CD4(+)CD25(hi) FOXP3(+) regulatory T cells (Tregs) maintain tolerance to self
      Ags. Their defective function is involved in the pathogenesis of multiple
      sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the
      mechanisms of such defective function are poorly understood. Recently, we
      reported that stimulation of TLR2, which is preferentially expressed by human
      Tregs, reduces their suppressive function and skews them into a Th17-like
      phenotype. In this study, we tested the hypothesis that TLR2 activation is
      involved in reduced Treg function in MS. We found that Tregs from MS patients
      expressed higher levels of TLR2 compared with healthy controls, and stimulation
      with the synthetic lipopeptide Pam3Cys, an agonist of TLR1/2, reduced Treg
      function and induced Th17 skewing in MS patient samples more than in healthy
      controls. These data provide a novel mechanism underlying diminished Treg
      function in MS. Infections that activate TLR2 in vivo (specifically through
      TLR1/2 heterodimers) could shift the Treg/Th17 balance toward a proinflammatory
      state in MS, thereby promoting disease activity and progression.

PMID- 25980008
TI  - A synthetic M protein peptide synergizes with a CXC chemokine protease to induce
      vaccine-mediated protection against virulent streptococcal pyoderma and
      bacteremia.
AB  - Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are
      highly prevalent in the tropics, in developing countries, and in the Indigenous
      populations of developed countries. These infections and their sequelae are
      responsible for almost 500,000 lives lost prematurely each year. A synthetic
      peptide vaccine (J8-DT) from the conserved region of the M protein has shown
      efficacy against disease that follows i.p. inoculation of bacteria. By developing
      a murine model for infection that closely mimics human skin infection, we show
      that the vaccine can protect against pyoderma and subsequent bacteremia caused by
      multiple GAS strains, including strains endemic in Aboriginal communities in the
      Northern Territory of Australia. However, the vaccine was ineffective against a
      hypervirulent cluster of virulence responder/sensor mutant GAS strain; this
      correlated with the strain's ability to degrade CXC chemokines, thereby
      preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the
      streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a
      combination vaccine that is highly effective in blocking CXC chemokine
      degradation and permits opsonic Abs to kill the bacteria. Mice receiving the
      combination vaccine were strongly protected against pyoderma and bacteremia, as
      evidenced by a 100-1000-fold reduction in bacterial burden following challenge.
      To our knowledge, a vaccine requiring Abs to target two independent virulence
      factors of an organism is unique.

PMID- 25980007
TI  - Polymicrobial Sepsis Increases Susceptibility to Chronic Viral Infection and
      Exacerbates CD8+ T Cell Exhaustion.
AB  - Patients who survive sepsis display suppressed immune functions, often manifested
      as an increased susceptibility to secondary infections. Recently, using a cecal
      ligation and puncture (CLP) model of sepsis, we showed that sepsis induces
      substantial and long-lasting changes in the available naive CD8(+) T cell
      repertoire affecting the capacity of the host to respond to newly encountered
      acute infections. However, the extent to which sepsis changes the host
      susceptibility to chronic infection and affects CD8(+) T cell responses is
      currently unknown. In this study, we demonstrate that inbred and outbred mice
      recovering from a septic event are more susceptible to lymphocytic
      choriomeningitis virus (LCMV) clone-13 infection exhibited by mortality and viral
      burden. Primary virus-specific CD8(+) T cells in LCMV clone-13-infected septic
      mice displayed exacerbated CD8(+) T cell exhaustion illustrated by increased
      inhibitory molecule expression (e.g., programmed cell death 1, lymphocyte
      activation gene 3, and 2B4) and diminished Ag-driven cytokine production (e.g.,
      IFN-gamma, TNF-alpha) compared with similarly infected sham-treated mice.
      Importantly, therapeutic inhibitory molecule dual blockade (anti-PD-L1 and anti
      lymphocyte-activation gene 3) increased the number of circulating LCMV-specific
      CD8(+) T cells, and improved CD8(+) T cell function and pathogen control in
      chronically infected septic mice. Together, these results illustrate that
      polymicrobial sepsis compromises the overall health of the host leading to
      increased vulnerability to chronic infection and exacerbated CD8(+) T cell
      exhaustion. Collectively, our findings suggest that septic survivors may be more
      susceptible and at greater risk for developing exhaustible CD8(+) T cells upon
      encountering a subsequent chronic infection. 

PMID- 25980009
TI  - Haploinsufficiency for Stard7 is associated with enhanced allergic responses in
      lung and skin.
AB  - Allergic asthma is a chronic inflammatory disorder that affects ~20% of the
      population worldwide. Microarray analyses of nasal epithelial cells from acute
      asthmatic patients detected a 50% decrease in expression of Stard7, an
      intracellular phosphatidylcholine transport protein. To determine whether loss of
      Stard7 expression promotes allergic responses, mice were generated in which one
      allele of the Stard7 locus was globally disrupted (Stard7 (+/-) mice). OVA
      sensitization and challenge of Stard7(+/-) mice resulted in a significant
      increase in pulmonary inflammation, mucous cell metaplasia, airway
      hyperresponsiveness, and OVA-specific IgE compared with OVA-sensitized/challenged
      wild-type (WT) mice. This exacerbation was largely Th2-mediated with a
      significant increase in CD4(+)IL-13(+) T cells and IL-4, IL-5, and IL-13
      cytokines. The loss of Stard7 was also associated with increased lung epithelial
      permeability and activation of proinflammatory dendritic cells in sensitized
      and/or challenged Stard7 (+/-) mice. Notably, OVA-pulsed dendritic cells from
      Stard7(+/-) mice were sufficient to confer an exaggerated allergic response in
      OVA-challenged WT mice, although airway hyperresponsiveness was greater in
      Stard7(+/-) recipients compared with WT recipients. Enhanced allergic responses
      in the lung were accompanied by age-dependent development of spontaneous atopic
      dermatitis. Overall, these data suggest that Stard7 is an important component of
      a novel protective pathway in tissues exposed to the extracellular environment.

PMID- 25980010
TI  - Altered distribution and increased IL-17 production by mucosal-associated
      invariant T cells in adult and childhood obesity.
AB  - Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells
      that regulate inflammatory responses through the rapid production of cytokines.
      In this article, we show that circulating MAIT cells are depleted in obese
      adults, and depletion is associated with diabetic status. Circulating MAIT cells
      more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in
      insulin resistance. MAIT cells were enriched in adipose tissue (AT) compared with
      blood. AT MAIT cells, but not circulating MAIT cells, were capable of producing
      IL-10. In AT from obese subjects, MAIT cells were depleted, were less likely to
      produce IL-10, and more frequently produced IL-17. Finally, we show that IL-17(+)
      MAIT cells are also increased in childhood obesity, and altered MAIT cell
      frequencies in obese children are positively associated with insulin resistance.
      These data indicate that MAIT cells are enriched in human AT and display an IL
      17(+) phenotype in both obese adults and children, correlating with levels of
      insulin resistance. The alterations in MAIT cells may be contributing to obesity
      related sterile inflammation and insulin resistance.

PMID- 25980011
TI  - Amino acid metabolism inhibits antibody-driven kidney injury by inducing
      autophagy.
AB  - Inflammatory kidney disease is a major clinical problem that can result in end
      stage renal failure. In this article, we show that Ab-mediated inflammatory
      kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was
      inhibited by amino acid metabolism and a protective autophagic response. The
      metabolic signal was driven by IFN-gamma-mediated induction of indoleamine 2,3
      dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress
      response dependent on the eIF2alpha kinase general control nonderepressible 2
      (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in
      glomeruli and reduced macrophage recruitment to the kidney during the incipient
      stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or
      genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to
      fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or
      treating mice with a GCN2 agonist induced autophagy and protected mice from
      nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven
      nephropathy showed increased IDO1 abundance and stress gene expression. Thus,
      these findings support the hypothesis that the IDO-GCN2 pathway in glomerular
      stromal cells is a critical negative feedback mechanism that limits inflammatory
      renal pathologic changes by inducing autophagy.

PMID- 25980012
TI  - Cutting Edge: Caspase-11 Limits the Response of CD8+ T Cells to Low-Abundance and
      Low-Affinity Antigens.
AB  - Inflammatory caspases, including caspase-11, are upregulated in CD8(+) T cells
      after Ag-specific activation, but little is known about their function in T
      cells. We report that caspase-11-deficient (Casp11(-/-)) T cells proliferated
      more readily in response to low-affinity and low-abundance ligands both in vitro
      and in vivo due to an increased ability to signal through the TCR. In addition to
      increased numbers, Casp11(-/-) T cells had enhanced effector function compared
      with wild-type cells, including increased production of IL-2 and reduced
      expression of CD62L. Casp11(-/-) T cells specific for endogenous Ags were more
      readily deleted than wild-type cells. These data indicate that caspase-11
      negatively regulates TCR signaling, possibly through its ability to regulate
      actin polymerization, and inhibiting its activity could enhance the expansion and
      function of low-affinity T cells. 

PMID- 25980013
TI  - Platelet-activating factor receptor contributes to antileishmanial function of
      miltefosine.
AB  - Miltefosine [hexadecylphosphocholine (HPC)] is the only orally bioavailable drug
      for the disease visceral leishmaniasis, which is caused by the protozoan parasite
      Leishmania donovani. Although miltefosine has direct leishmanicidal effects,
      evidence is mounting for its immune system-dependent effects. The mechanism of
      such indirect antileishmanial effects of miltefosine remains to be discovered. As
      platelet-activating factor and HPC share structural semblances and both induce
      killing of intracellular Leishmania, we surmised that platelet-activating factor
      (PAF) receptor had a significant role in the antileishmanial function of
      miltefosine. The proposition was supported by molecular dynamic simulation of HPC
      docking into PAF receptor and by comparison of its leishmanicidal function on PAF
      receptor-deficient macrophages and mice under HPC treatment. We observed that
      compared with wild-type macrophages, the PAF receptor-deficient macrophages
      showed 1) reduced binding of a fluorescent analog of HPC, 2) decreased TNF-alpha
      production, and 3) lower miltefosine-induced killing of L. donovani. Miltefosine
      exhibited significantly compromised leishmanicidal function in PAF receptor
      deficient mice. An anti-PAF receptor Ab led to a significant decrease in
      miltefosine-induced intracellular Leishmania killing and IFN-gamma production in
      a macrophage-T cell coculture system. These results indicate significant roles
      for PAF receptor in the leishmanicidal activity of HPC. The findings open new
      avenues for a more rational understanding of the mechanism of action of this drug
      as well as for improved therapeutic strategies.

PMID- 25980014
TI  - Endoplasmic reticulum and oxidant stress mediate nuclear factor-kappaB activation
      in the subfornical organ during angiotensin II hypertension.
AB  - Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in
      the brain circumventricular subfornical organ (SFO) mediate the central
      hypertensive actions of Angiotensin II (ANG II). However, the downstream
      signaling events remain unclear. Here we tested the hypothesis that angiotensin
      type 1a receptors (AT1aR), ER stress, and ROS induce activation of the
      transcription factor nuclear factor-kappaB (NF-kappaB) during ANG II-dependent
      hypertension. To spatiotemporally track NF-kappaB activity in the SFO throughout
      the development of ANG II-dependent hypertension, we used SFO-targeted adenoviral
      delivery and longitudinal bioluminescence imaging in mice. During low-dose
      infusion of ANG II, bioluminescence imaging revealed a prehypertensive surge in
      NF-kappaB activity in the SFO at a time point prior to a significant rise in
      arterial blood pressure. SFO-targeted ablation of AT1aR, inhibition of ER stress,
      or adenoviral scavenging of ROS in the SFO prevented the ANG II-induced increase
      in SFO NF-kappaB. These findings highlight the utility of bioluminescence imaging
      to longitudinally track transcription factor activation during the development of
      ANG II-dependent hypertension and reveal an AT1aR-, ER stress-, and ROS-dependent
      prehypertensive surge in NF-kappaB activity in the SFO. Furthermore, the increase
      in NF-kappaB activity before a rise in arterial blood pressure suggests a causal
      role for SFO NF-kappaB in the development of ANG II-dependent hypertension.

PMID- 25980015
TI  - Reply to letter to the editor: to D2O or not to D2O? What are the reasons we D2O
      it at all?

PMID- 25980016
TI  - Building Data Infrastructure to Evaluate and Improve Quality: PCORnet.

PMID- 25980017
TI  - Erratum.

PMID- 25980018
TI  - Choosing Wisely Canada cancer list: ten low-value or harmful practices that
      should be avoided in cancer care.
AB  - PURPOSE: Choosing Wisely Canada, modeled after Choosing Wisely in the United
      States, is intended to identify low-value or potentially harmful practices
      relevant to the Canadian health care environment. Our objective was to use
      multidisciplinary, pan-Canadian, physician-based consensus to identify a list of
      low-value or harmful cancer practices frequently used in Canada. METHODS: A Task
      Force convened by the Canadian Partnership Against Cancer included physician
      representation from the Canadian Society of Surgical Oncology, Canadian
      Association of Medical Oncologists, and Canadian Association of Radiation
      Oncology, and an expert advisor. The methodology included four phases: identify
      potentially relevant items, develop a long list, refine and reduce the long list
      to a short list, and select and endorse a final list. A framework-driven
      consensus process and a series of electronic surveys and voting processes were
      used to capture consensus. RESULTS: Sixty-six potentially relevant cancer-related
      practices were identified. The long list (41 practices) was reduced to a short
      list of 19 practices. Of the 10 practices on the final list, five are completely
      new, and five are revisions or adaptations of practices from previous US society
      lists. Six of the 10 involve multiple disease sites, and four are disease-site
      specific. One relates to diagnosis, six relate to treatment, two relate to
      surveillance/survivorship, and one practice spans the cancer care continuum.
      CONCLUSION: The cancer list was developed in partnership with the Canadian
      Society of Surgical Oncology, Canadian Association of Medical Oncologists, and
      Canadian Association of Radiation Oncology. Using knowledge translation and
      exchange efforts, this list should empower patients with cancer and physicians to
      assist in a targeted conversation about the appropriateness and quality of
      individual patient care.

PMID- 25980019
TI  - Detecting unplanned care from clinician notes in electronic health records.
AB  - PURPOSE: Reduction in unplanned episodes of care, such as emergency department
      visits and unplanned hospitalizations, are important quality outcome measures.
      However, many events are only documented in free-text clinician notes and are
      labor intensive to detect by manual medical record review. METHODS: We studied
      308,096 free-text machine-readable documents linked to individual entries in our
      electronic health records, representing care for patients with breast, GI, or
      thoracic cancer, whose treatment was initiated at one academic medical center,
      Stanford Health Care (SHC). Using a clinical text-mining tool, we detected
      unplanned episodes documented in clinician notes (for non-SHC visits) or in coded
      encounter data for SHC-delivered care and the most frequent symptoms documented
      in emergency department (ED) notes. RESULTS: Combined reporting increased the
      identification of patients with one or more unplanned care visits by 32% (15%
      using coded data; 20% using all the data) among patients with 3 months of follow
      up and by 21% (23% using coded data; 28% using all the data) among those with 1
      year of follow-up. Based on the textual analysis of SHC ED notes, pain (75%),
      followed by nausea (54%), vomiting (47%), infection (36%), fever (28%), and
      anemia (27%), were the most frequent symptoms mentioned. Pain, nausea, and
      vomiting co-occur in 35% of all ED encounter notes. CONCLUSION: The text-mining
      methods we describe can be applied to automatically review free-text clinician
      notes to detect unplanned episodes of care mentioned in these notes. These
      methods have broad application for quality improvement efforts in which events of
      interest occur outside of a network that allows for patient data sharing.

PMID- 25980020
TI  - Should the sympathetic nervous system be a target to improve cardiometabolic risk
      in obesity?
AB  - The sympathetic nervous system (SNS) plays a key role in both cardiovascular and
      metabolic regulation; hence, disturbances in SNS regulation are likely to impact
      on both cardiovascular and metabolic health. With excess adiposity, in particular
      when visceral fat accumulation is present, sympathetic activation commonly
      occurs. Experimental investigations have shown that adipose tissue releases a
      large number of adipokines, cytokines, and bioactive mediators capable of
      stimulating the SNS. Activation of the SNS and its interaction with adipose
      tissue may lead to the development of hypertension and end-organ damage including
      vascular, cardiac, and renal impairment and in addition lead to metabolic
      abnormalities, especially insulin resistance. Lifestyle changes such as weight
      loss and exercise programs considerably improve the cardiovascular and metabolic
      profile of subjects with obesity and decrease their cardiovascular risk, but
      unfortunately weight loss is often difficult to achieve and sustain.
      Pharmacological and device-based approaches to directly or indirectly target the
      activation of the SNS may offer some benefit in reducing the cardiometabolic
      consequences of obesity. Preliminary evidence is encouraging, but more trials are
      needed to investigate whether sympathetic inhibition could be used in obesity to
      reverse or prevent cardiometabolic disease development. The purpose of this
      review article is to highlight the current knowledge of the role that SNS plays
      in obesity and its associated metabolic disorders and to review the potential
      benefits of sympathoinhibition on metabolic and cardiovascular functions. 

PMID- 25980021
TI  - Hyperhomocysteinemia inhibits satellite cell regenerative capacity through p38
      alpha/beta MAPK signaling.
AB  - Chronic failure in maintenance and regeneration of skeletal muscles leads to
      lower muscle mass (sarcopenia), muscle weakness, and poor response to injury.
      Evidence suggests that aberrant p38 MAPK signaling undermines the repair process
      after injury in aged mice. Previous studies have shown that hyperhomocysteinemia
      (HHcy) has been associated with muscle weakness and lower than normal body
      weights. However, whether or not HHcy condition also compromises skeletal muscle
      regenerative capabilities is not clear. In the current study, we show that CBS-/+
      mice, a model for HHcy condition, exhibited compromised regenerative function and
      cell proliferation upon injury. However, there was no significant difference in
      Pax7 expression levels in the satellite cells from CBS-/+ mouse skeletal muscles.
      Interestingly, the satellite cells from CBS-/+ mice not only exhibited diminished
      in vitro proliferative capabilities, but also there was heightened oxidative
      stress. In addition, there was enhanced p38 MAPK activation as well as p16 and
      p21 expression in the CBS-/+ mouse satellite cells. Moreover, the C2C12 myoblasts
      also exhibited higher p38 MAPK activation and p16 expression upon treatment with
      homocysteine in addition to enhanced ROS presence. Tissue engraftment potential
      and regeneration after injury were restored to some extent upon treatment with
      the p38-MAPK inhibitor, SB203580, in the CBS-/+ mice. These results together
      suggest that HHcy-induced diminished satellite cell proliferation involves
      excessive oxidative stress and p38 MAPK signaling. Our study further proposes
      that HHcy is a potential risk factor for elderly frailty, and need to be
      considered as a therapeutic target while designing the alleviation
      interventions/postinjury rehabilitation measures for adults with HHcy. 

PMID- 25980022
TI  - 5-HT1A receptors of the nucleus tractus solitarii facilitate sympathetic recovery
      following hypotensive hemorrhage in rats.
AB  - The role of serotonin in the hemodynamic response to blood loss remains
      controversial. Caudal raphe serotonin neurons are activated during hypotensive
      hemorrhage, and their destruction attenuates sympathetic increases following
      blood loss in unanesthetized rats. Caudal raphe neurons provide serotonin
      positive projections to the nucleus tractus solitarii (NTS), and disruption of
      serotonin-positive nerve terminals in the NTS attenuates sympathetic recovery
      following hemorrhage. Administration of 5-HT1A-receptor agonists following
      hemorrhage augments sympathetic-mediated increases in venous tone and tissue
      hypoxia. These findings led us to hypothesize that severe blood loss promotes
      activation of 5-HT1A receptors in the NTS, which facilitates sympathetic recovery
      and peripheral tissue perfusion. Here, we developed an adeno-associated viral
      vector encoding an efficacious small hairpin RNA sequence targeting the rat 5
      HT1A receptor. Unanesthetized rats subjected to NTS injection of the anti-rat 5
      HT1A small hairpin RNA-encoding vector 4 wk prior showed normal blood pressure
      recovery, but an attenuated recovery of renal sympathetic nerve activity (-6.4 +/
      12.9 vs. 42.6 +/- 15.6% baseline, P < 0.05) 50 min after 21% estimated blood
      volume withdrawal. The same rats developed increased tissue hypoxia after
      hemorrhage, as indicated by prolonged elevations in lactate (2.77 +/- 0.5 vs.
      1.34 +/- 0.2 mmol/l, 60 min after start of hemorrhage, P < 0.05). 5-HT1A mRNA
      levels in the commissural NTS were directly correlated with renal sympathetic
      nerve activity (P < 0.01) and inversely correlated with lactate (P < 0.05) 60 min
      after start of hemorrhage. The data suggest that 5-HT1A receptors in the
      commissural NTS facilitate tissue perfusion after blood loss likely by increasing
      sympathetic-mediated venous return. 

PMID- 25980023
TI  - Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen
      consumption via local vasodilation during graded handgrip exercise in older
      adults.
AB  - Human aging is associated with reduced skeletal muscle perfusion during exercise,
      which may be a result of impaired endothelium-dependent dilation and/or
      attenuated ability to blunt sympathetically mediated vasoconstriction. Intra
      arterial infusion of ascorbic acid (AA) increases nitric oxide-mediated
      vasodilation and forearm blood flow (FBF) during handgrip exercise in older
      adults, yet it remains unknown whether an acute oral dose can similarly improve
      FBF or enhance the ability to blunt sympathetic vasoconstriction during exercise.
      We hypothesized that 1) acute oral AA would improve FBF (Doppler ultrasound) and
      oxygen consumption (Vo2) via local vasodilation during graded rhythmic handgrip
      exercise in older adults (protocol 1), and 2) AA ingestion would not enhance
      sympatholysis in older adults during handgrip exercise (protocol 2). In protocol
      1 (n = 8; 65 +/- 3 yr), AA did not influence FBF or Vo2 during rest or 5% maximal
      voluntary contraction (MVC) exercise, but increased FBF (199 +/- 13 vs. 248 +/-
      16 ml/min and 343 +/- 24 vs. 403 +/- 33 ml/min; P < 0.05) and Vo2 (26 +/- 2 vs.
      34 +/- 3 ml/min and 43 +/- 4 vs. 50 +/- 5 ml/min; P < 0.05) at both 15 and 25%
      MVC, respectively. The increased FBF was due to elevations in forearm vascular
      conductance (FVC). In protocol 2 (n = 10; 63 +/- 2 yr), following AA, FBF was
      similarly elevated during 15% MVC (~ 20%); however, vasoconstriction to reflex
      increases in sympathetic activity during -40 mmHg lower-body negative pressure at
      rest (DeltaFVC: -16 +/- 3 vs. -16 +/- 2%) or during 15% MVC (DeltaFVC: -12 +/- 2
      vs. -11 +/- 4%) was unchanged. Our collective results indicate that acute oral
      ingestion of AA improves muscle blood flow and Vo2 during exercise in older
      adults via local vasodilation.

PMID- 25980025
TI  - Comment on "Radiation exposure induces inflammasome pathway activation in immune
      cells".

PMID- 25980024
TI  - Physiological response of cardiac tissue to bisphenol A: alterations in
      ventricular pressure and contractility.
AB  - Biomonitoring studies have indicated that humans are routinely exposed to
      bisphenol A (BPA), a chemical that is commonly used in the production of
      polycarbonate plastics and epoxy resins. Epidemiological studies have shown that
      BPA exposure in humans is associated with cardiovascular disease; however, the
      direct effects of BPA on cardiac physiology are largely unknown. Previously, we
      have shown that BPA exposure slows atrioventricular electrical conduction,
      decreases epicardial conduction velocity, and prolongs action potential duration
      in excised rat hearts. In the present study, we tested if BPA exposure also
      adversely affects cardiac contractile performance. We examined the impact of BPA
      exposure level, sex, and pacing rate on cardiac contractile function in excised
      rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to
      10(-9)-10(-4) M BPA. Left ventricular developed pressure and contractility were
      measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca(2+)
      transients were imaged from whole hearts and from neonatal rat cardiomyocyte
      layers. During sinus rhythm in female hearts, BPA exposure decreased left
      ventricular developed pressure and inotropy in a dose-dependent manner. The
      reduced contractile performance was exacerbated at higher pacing rates. BPA
      induced effects on contractile performance were also observed in male hearts,
      albeit to a lesser extent. Exposure to BPA altered Ca(2+) handling within whole
      hearts (reduced diastolic and systolic Ca(2+) transient potentiation) and
      neonatal cardiomyocytes (reduced Ca(2+) transient amplitude and prolonged Ca(2+)
      transient release time). In conclusion, BPA exposure significantly impaired
      cardiac performance in a dose-dependent manner, having a major negative impact
      upon electrical conduction, intracellular Ca(2+) handing, and ventricular
      contractility. 

PMID- 25980026
TI  - Response to comment on "Radiation exposure induces inflammasome pathway
      activation in immune cells".

PMID- 25980027
TI  - Kill or be killed.

PMID- 25980028
TI  - Pillars article: Perforin gene defects in familial hemophagocytic
      lymphohistiocytosis. Science. 1999. 286: 1957-1959.

PMID- 25980030
TI  - The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for
      Phosphatidylserine and Phosphatidylethanolamine.
AB  - The CD300a inhibitory receptor belongs to the CD300 family of cell surface
      molecules that regulate a diverse array of immune cell processes. The inhibitory
      signal of CD300a depends on the phosphorylation of tyrosine residues embedded in
      ITIMs of the cytoplasmic tail. CD300a is broadly expressed on myeloid and
      lymphoid cells, and its expression is differentially regulated depending on the
      cell type. The finding that CD300a recognizes phosphatidylserine and
      phosphatidylethanolamine, two aminophospholipids exposed on the outer leaflet of
      dead and activated cells, has shed new light on its role in the modulation of
      immune functions and in its participation in the host response to several
      diseases states, such as infectious diseases, cancer, allergy, and chronic
      inflammatory diseases. This review summarizes the literature on CD300a
      expression, regulation, signaling pathways, and ligand interaction, as well as
      its role in fine tuning immune cell functions and its clinical relevance. 

PMID- 25980029
TI  - Prospects for Therapeutic Targeting of MicroRNAs in Human Immunological Diseases.
AB  - MicroRNAs (miRNAs) are endogenous oligoribonucleotides with exciting therapeutic
      potential. Early studies established a clear role for miRNAs in leukocyte
      biology. The first miRNA-based therapy, miravirsen, is now in phase 2 clinical
      trials, making the reality of these therapies undeniable. The capacity for miRNAs
      to fine-tune inflammatory signaling make them attractive treatment targets for
      immunological diseases. Nonetheless, the degree of redundancy among miRNAs,
      coupled with the promiscuity of miRNA binding sites in the transcriptome, require
      consideration when designing miRNA-directed interventions. Altered miRNA
      expression occurs across a range of inflammatory conditions, including
      inflammatory bowel disease, arthritis, and diabetes. However, very few studies
      successfully treated murine models of immunological diseases with miRNA-based
      approaches. While discussing recent studies targeting miRNAs to treat
      immunological conditions, we also reflect on the risks of miRNA targeting and
      showcase some newer delivery systems that may improve the pharmacological profile
      of this class of therapeutics. 

PMID- 25980031
TI  - Correction: Vector-encoded Helicobacter pylori neutrophil-activating protein
      promotes maturation of dendritic cells with Th1 polarization and improved
      migration.

PMID- 25980032
TI  - Correction: The acute respiratory distress syndrome: from mechanism to
      translation.

PMID- 25980034
TI  - Complement Activation Correlates With Disease Severity and Contributes to
      Cytokine Responses in Plasmodium falciparum Malaria.
AB  - The impact of complement activation and its possible relation to cytokine
      responses during malaria pathology was investigated in plasma samples from
      patients with confirmed Plasmodium falciparum malaria and in human whole-blood
      specimens stimulated with malaria-relevant agents ex vivo. Complement was
      significantly activated in the malaria cohort, compared with healthy controls,
      and was positively correlated with disease severity and with certain cytokines,
      in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo
      stimulated blood specimens, in which complement inhibition significantly reduced
      IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement
      activation and complement-dependent release of inflammatory cytokines, of which
      IL-8/CXCL8 is particularly prominent. 

PMID- 25980036
TI  - Set of interviews.

PMID- 25979941
TI  - Acetogenesis from H2 plus CO2 and nitrogen fixation by an endosymbiotic
      spirochete of a termite-gut cellulolytic protist.
AB  - Symbiotic associations of cellulolytic eukaryotic protists and diverse bacteria
      are common in the gut microbial communities of termites. Besides cellulose
      degradation by the gut protists, reductive acetogenesis from H2 plus CO2 and
      nitrogen fixation by gut bacteria play crucial roles in the host termites'
      nutrition by contributing to the energy demand of termites and supplying nitrogen
      poor in their diet, respectively. Fractionation of these activities and the
      identification of key genes from the gut community of the wood-feeding termite
      Hodotermopsis sjoestedti revealed that substantial activities in the gut--nearly
      60% of reductive acetogenesis and almost exclusively for nitrogen fixation--were
      uniquely attributed to the endosymbiotic bacteria of the cellulolytic protist in
      the genus Eucomonympha. The rod-shaped endosymbionts were surprisingly identified
      as a spirochete species in the genus Treponema, which usually exhibits a
      characteristic spiral morphology. The endosymbionts likely use H2 produced by the
      protist for these dual functions. Although H2 is known to inhibit nitrogen
      fixation in some bacteria, it seemed to rather stimulate this important
      mutualistic process. In addition, the single-cell genome analyses revealed the
      endosymbiont's potentials of the utilization of sugars for its energy
      requirement, and of the biosynthesis of valuable nutrients such as amino acids
      from the fixed nitrogen. These metabolic interactions are suitable for the dual
      functions of the endosymbiont and reconcile its substantial contributions in the
      gut.

PMID- 25980035
TI  - Human CD8+ T-Cell Responses Against the 4 Dengue Virus Serotypes Are Associated
      With Distinct Patterns of Protein Targets.
AB  - BACKGROUND: All 4 dengue virus (DENV) serotypes are now simultaneously
      circulating worldwide and responsible for up to 400 million human infections each
      year. Previous studies of CD8(+) T-cell responses in HLA-transgenic mice and
      human vaccinees demonstrated that the hierarchy of immunodominance among
      structural versus nonstructural proteins differs as a function of the infecting
      serotype. This led to the hypothesis that there are intrinsic differences in the
      serotype-specific reactivity of CD8(+) T-cell responses. METHODS: We tested this
      hypothesis by analyzing serotype-specific CD8(+) T-cell reactivity in naturally
      infected human donors from Sri Lanka and Nicaragua, using ex vivo interferon
      gamma-specific enzyme-linked immunosorbent spot assays. RESULTS: Remarkably
      similar and clear serotype-specific patterns of immunodominance in both cohorts
      were identified. Pooling of epitopes that accounted for 90% of the interferon
      gamma response in both cohorts resulted in a global epitope pool. Its reactivity
      was confirmed in naturally infected donors from Brazil, demonstrating its global
      applicability. CONCLUSIONS: This study provides new insight into differential
      serotype-specific immunogenicity of DENV proteins. It further provides a
      potentially valuable tool for future investigations of CD8(+) T-cell responses in
      the typically small sample volumes available from patients with acute fever and
      children without requiring prior knowledge of either infecting DENV serotype or
      HLA type.

PMID- 25980037
TI  - Emerging and re-emerging infectious threats in the 21st century.

PMID- 25980038
TI  - Middle East respiratory syndrome coronavirus (MERS-CoV): current situation 3
      years after the virus was first identified.

PMID- 25980039
TI  - Plague in Madagascar:overview of the 2014-2015 epidemic season.

PMID- 25980040
TI  - Prematurity and perinatal neglect.

PMID- 25980041
TI  - Village prenatals.

PMID- 25980042
TI  - Responses to issue 110.

PMID- 25980044
TI  - [What is an update on antibacterial drug development?].

PMID- 25980043
TI  - Benign histology after pancreaticoduodenectomy for suspected malignancy. Lessons
      to be learned--a single centre experience.
AB  - The aim of the study was to perform a comprehensive analysis of patients with a
      benign final histology after pancreaticoduodenectomies (PD) for suspected
      pancreatic and periampullary cancer. MATERIAL AND METHODS: We searched the
      pathology database at the King's College Hospital for negative PD specimens
      submitted between January 2004-December 2010. Clinical, diagnostic,
      surgical,histopathological and outcome data were collected retrospectively.
      Pathology specimens and imaging results have been re-evaluated. A literature
      review was performed to identify factors affecting the incidence across centres.
      RESULTS: 469 PD were performed for presumed cancer. The incidence of benign
      disease encountered in this group was 7.25% (34/469). Autoimmune pancreatitis
      (AIP) was a finding in 26.47% (9/34) of cases. 17.65% of PD were complicated by a
      pancreatic leak and the overall mortality rate was 8.82%(3/34). Radiologists
      revised over 75% of pre-operative diagnoses. The incidence of benign disease was
      correlated with the overall centre experience and utilisation of CT imaging, but
      not ERCP or EUS. CONCLUSIONS: It is impossible with current diagnostics to
      entirely avoid cases of benign disease inpatients undergoing PD for suspected
      cancer. The mortality rate is higher in this group, but it is possible to avoid
      unnecessary procedures in experienced centres. AIP represents an important
      diagnostic entity, which should be actively pursued pre-operatively.

PMID- 25980045
TI  - [Two cases of conjunctival intraepithelial neoplasia in immunosuppressed
      patients].
AB  - Background: Conjunctival intraepithelial neoplasia (CIN) is a precursor lesion of
      conjunctival squamous cell carcinoma (SCC). CIN recurs frequently but progresses
      less aggressively than SCC. We report 2 cases of recurrent CIN in
      immunosuppressed patients. CASE 1: A 60-year-old woman had been taking oral
      immunosuppressive drugs for 30 years for systemic lupus erythematosus. In 2005,
      both conjunctival tumor and high serum SCC levels were noted. Biopsy revealed
      right eye CIN and left eye SCC, and extended resection was performed. In 2008,
      right eye CIN recurred accompanied by high serum SCC levels and another extended
      resection was performed. The patient was free from recurrence for 1 year until
      her death. CASE 2: A 43-year-old woman who had been taking oral immunosuppressive
      drugs for 3 years for nephrotic syndrome. She had twice undergone right corneal
      transplantation for keratoconus. In 2011, right conjunctival tumor and high serum
      SCC levels were noted. Biopsy revealed right eye CIN, for which an extended
      resection was performed. At present she remains free from recurrence. CONCLUSION:
      CIN can recur in immunosuppressed patients. We suggest that serum SCC levels be
      monitored to help detect recurrence.

PMID- 25980046
TI  - [Multimodal imaging of a case of acute syphilitic posterior placoid
      chorioretinitis].
AB  - BACKGROUND: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare
      manifestation of ocular syphilis. We report on multimodal imaging including
      ophthalmoscopy, spectral-domain optical coherence tomography (SD-OCT),
      fluorescein angiography (FA) and indocyanine green angiography (IA) of a case
      diagnosed with ASPPC. CASE: A 45-year-old man who was positive for human
      immunodeficiency virus presented with a 2-week history of visual loss in the
      right eye. CLINICAL FINDINGS: Ophthalmoscopy showed a unilateral yellowish lesion
      involving the macula. SD-OCT revealed absence of the photoreceptor inner segment
      ellipsoid as well as an absent external limiting membrane, and nodular elevations
      of the retinal pigment epithelium layer at the macula. Late IA demonstrated
      punctate hypofluorescent dots in diffuse hyperfluorescent area corresponding to
      the macular lesion. Serologic tests were positive for syphilis and the patient
      was treated with intravenous penicillin G. Visual acuity improved with treatment
      from 20/100 to 20/16 and the retinal appearance returned to normal. There was
      completely restored stratification of the outer retina after therapy. CONCLUSION:
      In the present case of ASPPC, the SD-OCT imaging demonstrated characteristic
      abnormalities including RPE nodularity which showed hypofluorescent dots on late
      IA.

PMID- 25980048
TI  - Using double occlusion checking system and Bi-digital O-Ring Test to determine
      the vertical dimension of occlusion for maxillofacial prosthodontics for patients
      with long-term pathophysiological condition.
AB  - Common practice of establishing occlusal vertical dimension by adopting
      traditional method for patients with long-term pathological conditions has left
      the results much less than desired, since the degree of pathological condition
      for each patient varies from one patient to another, and traditional methods to
      determine vertical dimension are mostly intended for normal patients. Ideally,
      the occlusal vertical dimension should be dictated by, and conformed to patient's
      comfort range for the physiological accommodation to each patient's condition.
      This article describes a method of a double checking system for occlusion
      determination by increasing vertical dimension of occlusion (VDO) by 1/2 mm each
      week to find the most comfort zone and beyond for patient, and then to gradually
      decrease 1/2 mm of the VDO each week to the original VDO to double check the
      comfort zone for the patient. During the process, Bi-Digital O-Ring Test was
      employed to corroborate, to determine, and to individualize the occlusal vertical
      dimension for patients with pathological abnormalities. Traditional methods of
      vertical dimension determination were merely used as a guiding reference in our
      treatment of those patients. Patient's comfort and discomfort were carefully
      recorded, compared and studied before the denture prosthesis was fabricated.

PMID- 25980047
TI  - New non-invasive safe, quick, economical method of detecting various cancers was
      found using QRS complex or rising part of T-wave of recorded ECGs. Cancers can be
      screened along with their biochemical parameters & therapeutic effects of any
      cancer treatments can be evaluated using recorded ECGs of the same individual.
AB  - There are many methods of detecting cancers including detection of cancer markers
      by blood test, (which is invasive, time consuming and relatively expensive),
      detection of cancers by non-invasive methods such as X-Ray, CT scan, and MRI &
      PET Scan (which are non-invasive and quick but very expensive). Our research was
      performed to develop new non-invasive, safe, quick economical method of detecting
      cancers and the 1st author already developed for clinically important non
      invasive new methods including early stage of present method using his method of
      localizing accurate organ representation areas of face, eyebrows, upper lip,
      lower lip, surface and dorsal part of the tongue, surface backs, and palm side of
      the hands. This accurate localization of the organ representation area of the
      different parts of the body was performed using electromagnetic field resonance
      phenomenon between 2 identical molecules or tissues based on our US patented non
      invasive method in 1993. Since year 2000, we developed the following non-invasive
      diagnostic methods that can be quickly identified by the patented simple non
      invasive method without using expensive or bulky instrument at any office or
      field where there is no electricity or instrument available. The following are
      examples of non-invasive quick method of diagnosis and treatment of cancers using
      different approaches: 1) Soft red laser beam scanning of different parts of body;
      2) By speaking voice; 3) Visible and invisible characteristic abnormalities on
      different organ representation areas of the different parts of the body, and 4)
      Mouth, Hand, and Foot Writings of both right and left side of the body. As a
      consequence of our latest research, we were able to develop a simple method of
      detecting cancer from existing recorded electrocardiograms. In this article, we
      are going to describe the method and result of clinical applications on many
      different cancers of different organs including lung, esophagus, breast, stomach,
      colon, uterus, ovary, prostate gland, as well as common bone marrow related
      malignancies such as Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Multiple Myeloma
      as well as Leukemia.

PMID- 25980049
TI  - Statistical analysis of 4 types of neck whiplash injuries based on classical
      meridian theory.
AB  - As one component of the Chinese medicine meridian system, the meridian sinew
      (Jingjin, (see text), tendino-musculo) is specially described as being for
      acupuncture treatment of the musculoskeletal system because of its dynamic
      attributes and tender point correlations. In recent decades, the therapeutic
      importance of the sinew meridian has become revalued in clinical application.
      Based on this theory, the authors have established therapeutic strategies of
      acupuncture treatment in Whiplash-Associated Disorders (WAD) by categorizing four
      types of neck symptom presentations. The advantage of this new system is to make
      it much easier for the clinician to find effective acupuncture points. This study
      attempts to prove the significance of the proposed therapeutic strategies by
      analyzing data collected from a clinical survey of various WAD using non
      supervised statistical methods, such as correlation analysis, factor analysis,
      and cluster analysis. The clinical survey data have successfully verified
      discrete characteristics of four neck syndromes, based upon the range of motion
      (ROM) and tender point location findings. A summary of the relationships among
      the symptoms of the four neck syndromes has shown the correlation coefficient as
      having a statistical significance (P < 0.01 or P < 0.05), especially with regard
      to ROM. Furthermore, factor and cluster analyses resulted in a total of 11
      categories of general symptoms, which implies syndrome factors are more related
      to the Liver, as originally described in classical theory. The hypothesis of
      meridian sinew syndromes in WAD is clearly supported by the statistical analysis
      of the clinical trials. This new discovery should be beneficial in improving
      therapeutic outcomes.

PMID- 25980050
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibacterial agents (2007)].
AB  - From October 2007 to September 2008, we collected the specimen from 362 patients
      with lower respiratory tract infections in 14 institutions in Japan, and
      investigated the susceptibilities of isolated bacteria to various antibacterial
      agents and patients' characteristics. Of 413 strains that were isolated from
      specimen (mainly from sputum) and assumed to be bacteria causing in infection,
      412 strains were examined. The isolated bacteria were: Staphylococcus aureus 65,
      Streptococcus pneumoniae 90, Haemophilus influenzae 88, Pseudomonas aeruginosa
      (non-mucoid) 53, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 19, and
      Moraxella catarrhalis 41. Of 65 S. aureus strains, those with 2 MUg/mL or less of
      MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4
      MUg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were
      38 (58.5%) and 27 (41.5%) strains, respectively. Against MSSA, imipenem had the
      most potent antibacterial activity and inhibited the growth of all strains at
      0.063 MUg/mL or less. Against MRSA, vancomycin and arbekacin showed the most
      potent activity and inhibited the growth of all the strains at 2 MUg/mL.
      Linezolid also showed the same activity as them. Carbapenems and penems showed
      the most potent activities against S. pneumoniae and in particular, panipenem
      inhibited the growth of all the strains at 0.063 MUg/mL or less. Imipenem and
      faropenem also had a preferable activity and inhibited the growth of all the
      strains at 0.25 and 1 MUg/mL, respectively. In contrast, there were high
      resistant strains (MIC: over 128 MUg/mL) for erythromycin (38.2%) and clindamycin
      (18.0%). Against H. influenzae, levofloxacin showed the most potent activity and
      its MIC90 was 0.063 MUg/mL or less. Meropenem showed the most potent activity
      against P. aeruginosa (mucoid) and its MIC90 was 0.5 MUg/mL. Against P.
      aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90
      was 2 MUg/mL. Against K. pneumoniae, cefozopran had the most potent activity and
      inhibited the growth of all the strains at 0.063 MUg/mL or less. Also, all the
      antibacterial agents except ampicillin generally showed a potent activity against
      M. catarrhalis and the MIC90 of them were 2 MUg/mL or less. The approximately
      half the number (45.9%) of the patients with respiratory infection were aged 70
      years or older. Bacterial pneumonia and chronic bronchitis accounted for 44.8%
      and 31.5% of all the respiratory infection, respectively. The bacteria frequently
      isolated from the patients with bacterial pneumonia were S. aureus (21.9%), S.
      pneumoniae (20.8%), and H. influenzae (18.6%). S. pneumoniae (27.1%), H.
      influenzae (24.0%) and P. aeruginosa (17.8%) also were frequently isolated from
      the patients with chronic bronchitis. Before the drug administration, the
      bacteria frequently isolated from the patients were S. pneumoniae (23.9%) and H.
      influenzae (23.6%). The bacteria frequently isolated from the patients treated
      with macrolides were S. pneumoniae, and their isolation frequencies were 34.8%.

PMID- 25980051
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibacterial agents (2008)].
AB  - From October 2008 to September 2009, we collected the specimen from 374 patients
      with lower respiratory tract infections in 15 institutions in Japan, and
      investigated the susceptibilities of isolated bacteria to various antibacterial
      agents and patients' characteristics. Of 423 strains that were isolated from
      specimen (mainly from sputum) and assumed to be bacteria causing in infection,
      421 strains were examined. The isolated bacteria were: Staphylococcus aureus 78,
      Streptococcus pneumoniae 78, Haemophilus influenzae 89, Pseudomonas aeruginosa
      (non-mucoid) 61, P. aeruginosa (mucoid) 19, Klebsiella pneumoniae 28, and
      Moraxella catarrhalis 32. Of 78 S. aureus strains, those with 2 MUg/mL or less of
      MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4
      MUg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were
      34 (43.6%) and 44 (56.4%) strains, respectively. Against MSSA, imipenem had the
      most potent antibacterial activity and inhibited the growth of all strains at
      0.063 MUg/mL or less. Against MRSA vancomycin and arbekacin showed the potent
      activity and inhibited the growth of all the strains at 1 and 2 MUg/mL,
      respectively. Linezolid also showed the great activity and inhibited the growth
      of all the strains at 1 MUg/mL. Carbapenems and penems showed the most potent
      activities against S. pneumoniae and panipenem inhibited the growth of all the
      strains at 0.125 MUg/mL. Imipenem and faropenem also had a preferable activity
      and inhibited the growth of all the strains at 0.25 and 1 MUg/mL, respectively.
      In contrast, there were high-resistant strains (MIC: > 128 MUg/mL) for
      erythromycin (43.6%) and clindamycin (19.2%). Against H. influenzae, levofloxacin
      showed the most potent activity and its MIC90 was 0.063 MUg/mL or less.
      Tobramycin showed the most potent activity against P. aeruginosa (mucoid) and its
      MIC90 was 2 MUg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin and
      ciprofloxacin had the most potent activity and its MIC90 was 2 MUg/mL. Against K.
      pneumoniae, cefozopran had the most potent activity and inhibited the growth of
      all the strains at 0.063 MUg/mL or less. All the antibacterial agents except
      ampicillin generally showed a potent activity against M. catarrhalis and the
      MIC90 of them were 2 MUg/mL or less. The majority number (57.7%) of the patients
      with respiratory infection were aged 70 years or older. Bacterial pneumonia and
      chronic bronchitis accounted for 40.9% and 32.9% of all the respiratory
      infection, respectively. The bacteria frequently isolated from the patients with
      bacterial pneumonia were S. aureus (20.5%), S. pneumoniae (21.1%), and H.
      influenzae (22.8%). S. aureus (21.7%) and P. aeruginosa (24.6%) also were
      frequently isolated from the patients with chronic bronchitis. The bacteria
      frequently isolated from the patients were S. pneumoniae (23.4%) and H.
      influenzae (25.1%) before administration of the antibacterial agents. The
      bacteria frequently isolated from the patients previously treated with cephems
      and macrolides were P. aeruginosa, and the isolation frequencies were 41.4% and
      40.0%, respectively.

PMID- 25980052
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibacterial agents (2009)].
AB  - From October 2009 to September 2010, we collected the specimen from 432 patients
      with lower respiratory tract infections in 16 institutions in Japan, and
      investigated the susceptibilities of isolated bacteria to various antibacterial
      agents and patients' characteristics. All of 479 strains that were isolated from
      specimen (mainly from sputum) and assumed to be bacteria causing in infection,
      were examined. The isolated bacteria were: Staphylococcus aureus 90,
      Streptococcus pneumoniae 74, Haemophilus influenzae 82, Pseudomonas aeruginosa
      (non-mucoid) 60, P. aeruginosa (mucoid) 31, Klebsiella pneumoniae 41, and
      Moraxella catarrhalis 34. Of 90 S. aureus strains, those with 2 MUg/mL or less of
      MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4
      MUg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were
      43 (47.8%) and 47 (52.2%) strains, respectively. Against MSSA, imipenem had the
      most potent antibacterial activity and inhibited the growth of all strains at
      0.063 MUg/mL or less. Against MRSA, vancomycin and arbekacin showed the potent
      activity and inhibited the growth of all the strains at 2 and 4 MUg/mL,
      respectively. Linezolid also showed the great activity and inhibited the growth
      of all the strains at 2 MUg/mL. Carbapenems and penems showed the most potent
      activities against S. pneumoniae and panipenem inhibited the growth of all the
      strains at 0.125 MUg/mL. Imipenem and faropenem also had a preferable activity
      and inhibited the growth of all the strains at 0.25 and 0.5 MUg/mL, respectively.
      In contrast, there were high-resistant strains (MIC: > 128 MUg/mL) for
      erythromycin (51.4%) and clindamycin (35.1%). Against H. influenzae, levofloxacin
      showed the most potent activity and its MIC90 was 0.063 MUg/mL or less. Meropenem
      showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was
      1 MUg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin had the most
      potent activity and its MIC90 was 2 MUg/mL. Against K. pneumoniae, cefozopran had
      the most potent activity and inhibited the growth of all the strains at 0.125
      MUg/mL or less. All the antibacterial agents except ampicillin generally showed a
      potent activity against M. catarrhalis and the MIC90 of them were 2 MUg/mL or
      less. The majority number (60.0%) of the patients with respiratory infection was
      aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for
      48.8% and 31.7% of all the respiratory infection, respectively. The bacteria
      frequently isolated from the patients with bacterial pneumonia were S. aureus
      (21.5%), S. pneumoniae (20.2%), and H. influenzae (16.7%). S. aureus (21.9%) and
      P. aeruginosa (20.0%) also were frequently isolated from the patients with
      chronic bronchitis. The bacteria frequently isolated from the patients were S.
      pneumoniae (21.5%) and H. influenzae (20.5%) before administration of the
      antibacterial agents. The bacteria frequently isolated from the patients
      previously treated with cephems and macrolides were P. aeruginosa, and the
      isolation frequencies were 28.6% and 47.2%, respectively.

PMID- 25980053
TI  - [Effective use of heterologous hosts for characterization of biosynthetic enzymes
      allows production of natural products and promotes new natural product
      discovery].

PMID- 25980054
TI  - A year of Ebola. New signs of hope.

PMID- 25980055
TI  - Unlocking the secrets of PTSD.

PMID- 25980056
TI  - Hopes run high for passing doc fix when Senate returns in April.

PMID- 25980057
TI  - Tenet's Baylor deal builds network strategy.

PMID- 25980058
TI  - Questions mount onVA cost overruns.

PMID- 25980059
TI  - Feds propose tougher look at whether EHRs work.

PMID- 25980060
TI  - Network squeeze. Controversies continue over narrow health plans.

PMID- 25980061
TI  - Demand grows for care coordinators.

PMID- 25980062
TI  - Future of Medicaid hospital improvement program in doubt.

PMID- 25980063
TI  - The SGR fix helps the value-based care evolution.

PMID- 25980064
TI  - Two ways to make ACOs work better.

PMID- 25980065
TI  - Curbing injuries from moving patients.

PMID- 25980066
TI  - Insurers don't want to share savings from reduced utilization.

PMID- 25980067
TI  - Largest physician staffing firms. Ranked by number of physician recruiters as of
      March 2015.

PMID- 25980068
TI  - The skinny on diet soda. Is it time to kick artificial sugars out of the can?

PMID- 25980069
TI  - The cancer gap. No two cancers are alike. But what will it take to give every
      patient equal care?

PMID- 25980070
TI  - Blues' tax-exempt loss raises red flag.

PMID- 25980071
TI  - Hospital health plans heighten tensions with insurers.

PMID- 25980072
TI  - Recovering construction industry banks on outpatient growth.

PMID- 25980073
TI  - Integrated construction model may have saved $200 million on new UCSF complex.

PMID- 25980075
TI  - Hot zones/dead zones. Local factors produce patchy national shift to ACOs.

PMID- 25980074
TI  - Construction gets greener, but fewer projects abroad.

PMID- 25980076
TI  - Draconian healthcare cuts at heart of House budget plan.

PMID- 25980077
TI  - Providers, payers need to mend relationships to make value-based care system
      successful.

PMID- 25980078
TI  - New app aids Mount Sinai asthma research.

PMID- 25980079
TI  - Value-based care is about outcomes, not just cutting cost.

PMID- 25980080
TI  - Top Medicaid managed-care insurers. Based on number of Medicaid covered lives as
      of the third quarter of 2014.

PMID- 25980081
TI  - Healthcare leaders mull their options as they wait for King ruling.

PMID- 25980082
TI  - Dramatic day at high court leaves everyone guessing about ACA's future.

PMID- 25980083
TI  - Medical-device makers step up lobbying to kill ACA tax.

PMID- 25980084
TI  - Hospital staff injuries will go public with OSHA rule.

PMID- 25980085
TI  - Non-interoperable directives: end-of-life wishes and EHRs don't yet mesh.

PMID- 25980086
TI  - Lifesavers or kickbacks? Critics say patient-assistance programs help keep drug
      prices high.

PMID- 25980087
TI  - The high price of precision medicine.

PMID- 25980088
TI  - Integrated delivery networks: is the whole less than sum of the parts?

PMID- 25980089
TI  - IT firm lets providers share clinical protocols.

PMID- 25980090
TI  - Co-op plans' successes deserve more attention than a failure or two.

PMID- 25980091
TI  - Largest healthcare fraud settlements from 2014. Ranked by settlement amount under
      the False Claims Act and other statutes.

PMID- 25980092
TI  - [Relationship between bizygomatic width and the size of maxillary anterior teeth
      among young Senegalese black people recruited in army].
AB  - INTRODUCTION: Prosthetic teeth size and placement must be in perfect harmony with
      the bucco-facial structures for a successful and esthetic removable prosthesis.
      This study aimed to determine among young Senegalese black people facial index
      estimating maxillary central incisor width and distance between canine points
      starting from bizygomatic width. PATIENTS AND METHODS: 621 black Senegalese
      participated to this transversal study. Measurements were made using
      anthropometric slide caliper and electronic slide caliper. The comparative
      analysis was carried out by the test t of Student. The correlative analysis used
      the chi-square test. The risk of error was fixed at 5%. RESULTS: Positive
      correlations were found between variables. Distance between canine points was
      significantly (p = 0.000) correlated to bizygomatic width and central incisor
      width. Using bizygomatic width, the average dividing factors to estimate central
      incisor width and distance between canine points were respectively 15.13 and
      3.75. CONCLUSION: Distance between canine points and central incisor width can be
      given starting from bizygomatic width, as guide of selecting maxillary anterior
      prosthetic teeth width.

PMID- 25980093
TI  - [Study of remains and dental wastes of a First World War German rest camp].
AB  - INTRODUCTION: This article presents the analysis of dental remains and waste from
      the dental office of a German rest camp of the First World War in order to study
      the living conditions of the soldiers, the care policy and the prosthetic
      rehabilitation techniques used in this context. MATERIALS AND METHODS: The study
      included both dental and prosthetic remains, revealed during the excavation. The
      criteria to determine dental and periodontal health were the presence or absence
      of caries, wear, tartar and periodontal lesion. Location, severity and frequency
      of each of these parameters were examined. Regarding the prosthetic remains, the
      type of prosthesis and the materials used were determined. RESULTS: Three hundred
      and twenty seven (327) dental remains were analyzed. A high prevalence of large
      caries, especially in the molar areas, was highlighted. The incisal areas had
      however more wear and tartar. 183 casts of plaster dental arcade allowed to
      highlight a significant proportion of posterior edentulous. Prosthetic remains
      and laboratory waste revealed the use of vulcanite and porcelain for making
      dentures.

PMID- 25980094
TI  - Influence of clinical experience on oral health attitude and behaviour of dental
      students attending a Nigerian university.
AB  - OBJECTIVE: To evaluate the self-reported oral health attitudes and behaviour
      among the clinical dental students and to compare the influence of clinical
      experience on oral health attitudes and behaviour among dental students at the
      different clinical years in the University of Benin using the modified Hiroshima
      University Dental Behavior Inventory (HU-DBI). METHODS: The study involved 156
      clinical dental students from the University of Benin, Benin City, Nigeria.
      Demographic data were obtained for age and gender from 4th, 5th and 6th year
      clinical students. A modified English version of HU-DBI survey consisted of 22
      items with dichotomous responses (yes-no) was used in this study. Descriptive
      statistics was performed for age and clinical level of education. Chi-square text
      was applied to the percentages of responses. Tamhane's T2 post-hoc multiple
      comparison for pairwise comparison of the three clinical levels of students was
      done to determine the differences. Test significance was set at P < 0.05.
      RESULTS: The response rate was 87.2%. The mean age of the respondents was 26.2 +
      2.4 years. A total of 62 (39.7%) respondents were females and 94 (60.3%) males.
      Statistically significant differences were found among the various clinical
      levels of dental students for previous visit to the dentist office, visiting the
      dentist unless there is toothache, brushing the teeth twice daily and the
      prevention of gum disease with tooth brushing alone. CONCLUSION: There was
      improvement in the dental students' oral health behaviour and attitudes with
      increasing level of dental education.

PMID- 25980095
TI  - [Epidemiology and clinic of dental extractions in University Teaching Hospital
      Yalgado Ouedraogo, (Burkina Faso)].
AB  - INTRODUCTION: The consequences of tooth loss are often severe for the patient:
      aesthetic deficit, decreased masticatory coefficient, malnutrition... The
      objective of this study was to describe the epidemiological and clinical aspects
      of dental extractions of patients attending the University Teaching Hospital
      Yalgado Ouedraogo (UTHYO). PATIENTS AND METHODS: It was a descriptive cross
      sectional retrospective study on a sample of 65 patients who received a dental
      extraction at least in dental surgery of the UTHYO. RESULTS: The sample consisted
      of 33 (50.8%) patients female to 32 (49.2%) cases of male, or a sex ratio of
      0.96. The average age was 36,55 year-old with extremes of 5 and 84 years.
      Employees and pupils were the most affected by extractions (33 cases; 47,8% and
      22 cases; 33,8%). Dental extractions were more frequent in patients aged between
      25 and 60 years. A total of 84 tooth extraction was performed in 65 patients, an
      average of 1.3 tooth extracted per patient. The most often extracted tooth was
      the third lower molar (17 cases, 22,95%). The canine was the less often extracted
      tooth (1 case, 1,35%). Dental decay and its complications (57 cases, 67,87%) and
      periodontal diseases (10 cases, 11,90%) were the commonest reasons for dental
      extractions. CONCLUSION: Dental decay and periodontal diseases are the most
      important causes of dental extractions. Particular emphasis should be placed on
      prevention and early care of teeth.

PMID- 25980096
TI  - Dentoalveolar abscess: A case of poor dental visit and unawareness of dental
      treatment ?
AB  - OBJECTIVE: Dentoalveolar abscess is a serious complication that may arise from
      untreated dental caries, periodontal disease, pericoronitis and facial fractures.
      The objective of study was to ascertain the dental visit pattern and awareness of
      dental treatment among patients attending a secondary oral health facility in
      Benin-City with dentoalveolar abscess. MATERIALS AND METHODS: A total of 50
      patients that presented with dentoalveolar abscess in the Dental Clinic of
      Central Hospital between September, 2012 and July, 2013 constituted the study
      population. Data was collected using unstructured in-depth interview, following a
      topic guide. RESULTS: Of the 50 patients, 29 (58%) were females, while 21 (42%)
      were males. Age range was between 3-67 years and the educational status of the
      patients ranged from illiterate to graduates of tertiary institution. Time
      interval between onset of pain and presentation of swelling was 1 day to 10
      years. Forty-five patients (90%) have heard of dentists. A total of 27 (60%)
      reported teeth extraction as the only treatment carried out by dentists, 12 (27%)
      extraction/restoration replacement/treatment and 5 (13%) treatment only. Thirty
      seven patients (74%) were first time clinic attendees, 7 (14%) were second time
      clinic attendees and 6 (12%) were three times and more clinic attendees.
      CONCLUSION: This study revealed that patients attending secondary oral health
      facility with dentoalveolar abscess were dominantly first time dental clinic
      attendees and exhibited low awareness of treatments offered by dentists. There is
      need to further investigate the barriers to preventive visits and to improve of
      awareness of dental treatment among previous dental clinic attendees.

PMID- 25980097
TI  - [Ultra-structural study of Ni-Cr alloys used in joint prosthesis].
AB  - Ni-Cr alloys used in denture set, which have excellent mechanical properties,
      have a chemical and electrochemical inertia that depends on their composition and
      their microstructure. The objective of our work was to study the ultrastructure
      of the Ni-Cr alloy exposed to a free corrosion and a chemical analysis of surface
      depending on its composition. For this, five electrodes Ni-Cr alloy were prepared
      at the prosthesis laboratory by varying their composition. An analysis of the
      ultrastructure of the samples made by Scanning Electron Microscopy (SEM) samples
      was performed as well as a chemical analysis of their spectra. Prior to any
      manipulation, analysis by SEM of electrode number 5 (100% new metal) shows an
      altered surface. The electrode 3 (75% new metal) also presents an uneven surface.
      After a week in a free corrosion in Meyer solution at pH = 6.5, the electrode 5
      shows a widespread intergranular and pitting corrosion. The same electrode 3 (75%
      new metal) after one week immersion in Ringer's solution at pH 7.9, shows a
      widespread intergranular and pitting corrosion. After electrochemical testing in
      Ringer's solution at pH 5, the SEM for electrode 1 (100% recovered metal) shows a
      very rugged structure with an important crevice corrosion. The composition and
      terms of shaping the Ni-Cr alloy influence its microstructure and at the same
      time its electrochemical behavior.

PMID- 25980098
TI  - Midwifing a movement.

PMID- 25980099
TI  - Oligohydramnios.

PMID- 25980100
TI  - Preeclampsia and nutritional priorities.

PMID- 25980101
TI  - Sick pregnancies.

PMID- 25980102
TI  - How to turn a breech baby to head-down.

PMID- 25980103
TI  - Stories to learn from: toxemia in pregnancy.

PMID- 25980104
TI  - Preeclampsia.

PMID- 25980105
TI  - Assuring healthy babies: weight gain in pregnancy.

PMID- 25980106
TI  - Doris Haire, 1925-2014; a tribute.

PMID- 25980107
TI  - Mercier Therapy: the history behind it.

PMID- 25980108
TI  - Public breastfeeding awareness project.

PMID- 25980109
TI  - The deadly itch: how my midwives saved my babies' lives.

PMID- 25980110
TI  - Pelvic organ prolapse: a proactive approach to prevention.

PMID- 25980111
TI  - Emma Oceane.

PMID- 25980112
TI  - The paleo lifestyle in pregnancy.

PMID- 25980113
TI  - Newborns: their biological and theological uniqueness.

PMID- 25980114
TI  - Calcium and vitamin C supplements: effects on preterm birth and preeclampsia.

PMID- 25980115
TI  - The childless midwife: Justine Siegemund of eighteenth-century Germany.

PMID- 25980116
TI  - Sowing seeds of change.

PMID- 25980117
TI  - Birth in India: an update.

PMID- 25980118
TI  - The power of placenta for hemorrhage control.

PMID- 25980119
TI  - Re: "Helping a mother with twins: choose your words wisely" by Mary Cooper, issue
      110.

PMID- 25980120
TI  - Uterine prolapse: is there a way to prevent it? Have you experienced it in your
      practice?

PMID- 25980121
TI  - How did/do you feel when breastfeeding in public?

PMID- 25980122
TI  - [An optimal automatic selection algorithm of permissible source region applied in
      bioluminescence tomography].
AB  - OBJECTIVE: An optimal automatic selection method of permissible source region is
      proposed to reduce the ill-conditioned and ill-posed problems in the
      reconstruction of the light source in bioluminescence tomography. METHODS: The 2D
      images captured by CCD are mapped into surface light irradiance distribution
      based on the light propagating model. The relation matrix between the source and
      light distribution is obtained by finite element method. Permissive source region
      is determined by using the automatic selection method proposed in this paper, and
      then Tikhonov regularization is applied to reconstruct the light source. RESULTS:
      The center point distance between the optimal permissible source region and true
      source is 1.26 mm, and the center point error of the reconstructed light source
      and true source is 0.47 mm, the volume error is 9.13 mm3. CONCLUSION: The optimal
      permissive source region selection strategy is effective to locate the permissive
      source region close to the true source, and reduces the reconstructed error due
      to subjective orientation of permissible source region. This proposed method is
      the basis of high precision source reconstruction in bioluminescence tomography.

PMID- 25980123
TI  - [Curvelet denoising algorithm for medical ultrasound image based on adaptive
      threshold].
AB  - The traditional denoising algorithm for ultrasound images would lost a lot of
      details and weak edge information when suppressing speckle noise. A new denoising
      algorithm of adaptive threshold based on curvelet transform is proposed in this
      paper. The algorithm utilizes differences of coefficients' local variance between
      texture and smooth region in each layer of ultrasound image to define fuzzy
      regions and membership functions. In the end, using the adaptive threshold that
      determine by the membership function to denoise the ultrasound image. The
      experimental text shows that the algorithm can reduce the speckle noise
      effectively and retain the detail information of original image at the same time,
      thus it can greatly enhance the performance of B ultrasound instrument.

PMID- 25980124
TI  - [Clinical data mining by exploring public MIMIC-II intensive care database].
AB  - This paper introduces a free and publicly open ICU database: multi-parameter
      intelligent monitoring in intensive care II: MIMIC-II, which has been built up
      and maintained by the laboratory of computational physiology at the Massachusetts
      Institute Technology, Beth Israel Deaconess Medical Center and Philips Healthcare
      over the past decade. This paper briefly introduces its infrastructure,
      implementation and applications in clinical studies. Clinical study pertaining to
      circadian variation in heart rate and blood pressure during sepsis is shown as a
      typical example of research performed with MIMIC-II. In this study, it was found
      there was significant difference in circadian variation in both heart rate and
      blood pressure between survival and non-survival groups in septic patients. This
      study tackled several important techniques necessary for the investigation of the
      circadian rhythm.

PMID- 25980125
TI  - [Theoretical model study about the application risk of high risk medical
      equipment].
AB  - OBJECTIVE: Research for establishing a risk monitoring theoretical model of high
      risk medical equipment at applying site. METHODS: Regard the applying site as a
      system which contains some sub-systems. Every sub-system consists of some risk
      estimating indicators. After quantizing of each indicator, the quantized values
      are multiplied with corresponding weight and then the products are accumulated.
      Hence, the risk estimating value of each subsystem is attained. Follow the
      calculating method, the risk estimating values of each sub-system are multiplied
      with corresponding weights and then the product is accumulated. The cumulative
      sum is the status indicator of the high risk medical equipment at applying site.
      The status indicator reflects the applying risk of the medical equipment at
      applying site. RESULT: Establish a risk monitoring theoretical model of high risk
      medical equipment at applying site. CONCLUSION: The model can monitor the
      applying risk of high risk medical equipment at applying site dynamically and
      specially.

PMID- 25980126
TI  - [The research of predicting neonatal sepsis in preterm infants].
AB  - This paper is dedicated to the research of predictive monitoring system for
      neonatal sepsis, and is mainly focused on the establishment of ECG acquisition
      platform in NICU, the ECG characteristic recognition method which is based on the
      slope threshold method and adaptive threshold method, and the predictive effect
      of clinical ECG data in predicting neonatal sepsis.

PMID- 25980127
TI  - [Development of portable uterine contraction pressure monitoring system].
AB  - For the high cost and mobility issues, a home uterine contraction pressure
      monitoring system based on Windows CE platform was developed. In this paper, the
      design of hardware circuit, micro-controller system and LabVIEW program based on
      Windows CE are discussed. The clinical validation experiment in hospital for this
      system was made and the experimental results show that this system complies with
      the trend that current medical equipment is becoming portable, homely and
      networked. Through real-time monitoring uterine contraction pressure, occurrence
      of premature birth and abortion can be prevented effectively.

PMID- 25980128
TI  - [Application and development of intelligent adjustable leg raising system].
AB  - OBJECTIVE: To develop an intelligent adjustable leg raising system which could
      realize the quantification and visualization of lower limbs' elevation angle and
      frequency. METHODS: We determined the pole adjustable length of thighs and cruses
      and the flexion angle range of hips and knees according to the requirements of
      clinical lower limb function rehabilitation, and made force analysis of hip's and
      knee's flexion motivation mechanism and clinical observation on its security and
      effectiveness. RESULTS: This device was small and compact in overall appearance,
      which could adjust the angle of the hips and knees bending and ankles turning
      alone. The force analysis of the hips and knees flexion power element was
      consistent with the design requirements. The preliminary studies showed the
      device could relieve pain, improve the range of motion and promote the
      rehabilitation, which was superior to that of the Brown Ska (P < 0.05).
      CONCLUSION: The intelligent adjustable leg raising system meets the requirements
      of clinical usage, which is suitable for different heights, and the flexion angle
      ranges of hips and knees are wide and in high accuracy, which is worth of being
      improved and generalized.

PMID- 25980129
TI  - [A rapid fetal ECG acquisition system based on FT245RL].
AB  - A rapid fetal ECG signal acquisition system is designed, which includes three
      modules: a front-end signal acquisition module, a micro control module and a PC
      software application module. The first two modules are accomplished through the
      ADS1294 and the STM32F103 chips, respectively, and the third one is developed in
      VC++ platform. By using the FT245RL chip, the proposed system implements the
      serial-parallel conversion communication between ARM and PC, improving the data
      transmission rate largely. Also, it has a simple structure, with low power
      consumption and high precision. Furthermore, it can collect fetal ECG signals
      from mother's abdominal wall and convert them into the 24-bit digital signals.

PMID- 25980130
TI  - [Calculation of MR radiofrequency specific energy absorption rate and clinical
      application].
AB  - This paper reviews the basic principles and calculation methods of MR specific
      absorption rate, discusses the clinical application of MR specific absorption
      rate.

PMID- 25980131
TI  - [The basic structure of heavy-ion tumor therapy facility].
AB  - Heavy-ions have the similar characteristic of depth-dose distribution with
      protons, but exhibit enhanced physical and radiobiological benefits. With
      increasing development in technical and clinical research, more facilities are
      being installed in the world. At the same time, many critical techniques of heavy
      ion therapy facility were optimized and completed. This paper classified and
      reviewed the basic structure of heavy-ion system equipments, especially the
      accelerator, gantry, nozzle , TPS.

PMID- 25980132
TI  - [Discussion on the electromagnetic compatibility testing and evaluation of radio
      frequency ablation catheter].
AB  - With the enforcement of YY 0505-2012, the testing items and evaluation points of
      radio frequency ablation catheter in electromagnetic compatibility field should
      be studied and discussed. Based on the requirements of relevant standards, this
      paper discusses on the testing items that should be applied and the evaluation
      points that should be focused on by analyzing the intended use and the structure
      of radio frequency ablation catheter, when it intends to apply registration
      individually with the basic knowledge of electromagnetic compatibility field.

PMID- 25980133
TI  - [Study on cytotoxicity tests of medical devices based on IC50].
AB  - To discuss IC50 application in cytotoxicity tests of medical devices, we firstly
      investigated the vibrating condition and endpoint of MTT method specified in ISO
      10993-5: 2009. Furthermore, we demonstrated the application of IC50 in the result
      evaluation of MTT method. The experimental results show that usage of IC50 in
      quantitative evaluation of MTT method is feasible.

PMID- 25980134
TI  - [Chemical performance comparison of repair mesh].
AB  - This article analyses the chemical test results of several common repair mesh,
      and concludes the currently several common repair mesh are safe and reliable.

PMID- 25980135
TI  - [Analysis on 567 cases of adverse events of the vaginal dilator].
AB  - OBJECTIVE: To investigate the risk factors of vaginal dilators by 567 adverse
      event reports, and to provide a reference for the reasonable use. METHODS: With
      retrospective case study, analyzed 567 reports induced by vaginal dilators by
      National Adverse Drug Reaction Monitoring Center in 2012. RESULTS: Expected
      treatment of disease might be relevant with severity of adverse events, while age
      was not the related factor; the influencing factor of consequences of grading was
      the classification of the cause of adverse events. CONCLUSION: Monitoring should
      be strengthen in order to reduce or avoid the vaginal dilator adverse events.

PMID- 25980136
TI  - [Analysis on the main difference and impact between IEC 60601-1 in Ed. 3.1 and GB
      9706.1-2007].
AB  - For the preparation of implementing IEC 60601-1 Ed. 3.1 in advance, this paper
      analyzes the main difference between IEC 60601-1 Ed. 3.1 and GB 9706.1-2007, and
      discusses the possible influence to medical device designing and testing.

PMID- 25980137
TI  - [Analysis on the development strategy for hearing aid fitting].
AB  - Based on the investigation and analysis of the current situation for hearing aid
      fitting, some analysis results and suggestions for the development of the
      industry are presented, including manufacturer, association for medical devices
      industry and supervision division.

PMID- 25980138
TI  - [Situation and suggestions on IVD industrial standards].
AB  - This paper briefly introduces the working procedure of in vitro diagnostic
      products (IVD) industrial standards, and elaborates the importance of
      professional standards for production and supervision. Based on the analysis of
      working progress during the past 10 years, some problems and countermeasures on
      project setting, participation, standard material, personnel training, work cycle
      are put forward, which are helpful for the future development of the IVD.

PMID- 25980139
TI  - [Research on the application of risk management to medical device].
AB  - Based on the analysis of risk management to Chinese medical device situation and
      deficiencies, provide some guidance for the application of risk management to
      medical device.

PMID- 25980140
TI  - [The research progress of SPECT/CT].
AB  - With the development of molecular imaging technology, incorporate multiple modes
      of medical imaging imaging techniques of SPECT/CT and PET/CT technology with a
      certain degree of development. But compared to SPECT/CT and PET/CT technologies,
      SPECT/CT far earlier than PET/CT technology to clinical applications, due to a
      variety of factors influence SPECT/CT far PET/CT clinical applications to grow
      faster. This article highlights the progress and problems of SPECT/CT technology.

PMID- 25980141
TI  - [Application research of protein test by using biuret reagent].
AB  - OBJECTIVE: To investigate the biuret reagent to detect proteins in the
      application, the impact of different test conditions for test results. METHODS:
      The biuret method to select three different instruments, reagents, calibrators
      are arranged in combination to form 27 sets of detection systems, each detection
      system is a combination of 5 serum samples for testing, 5 measured values
      obtained, the selection process normality good a serum for the study to determine
      the mean value of all AST after culling outliers obtained in order to calculate
      the various detection systems use a combination of biuret reagent to detect
      proteins bias. RESULTS: The use of different detection equipment to detect
      proteins biuret reagent bias, homogeneity of variance (P = 0.467), the difference
      was not statistically significant (F = 1.688, P = 0.421). different detection
      reagents using biuret reagent to detect proteins bias, homogeneity of variance (P
      = 0.574), a statistically significant difference (F = 5.784, P = 0.011).
      different calibrators use biuret reagent to detect proteins bias, homogeneity of
      variance (P = 0.467), the difference was statistically significant (F = 5.289, P
      = 0.000). CONCLUSION: Biuret reagent in the detection of protein applications,
      impact detection reagents and calibrators will test result, during the test than
      when it is necessary to detect deviation detection reagents and calibrators due
      to be considered.

PMID- 25980142
TI  - [The authorized considerations on the pre-clinical study of drug-eluting coronary
      stent system].
AB  - China Food and Drug Administration didn't issue any guideline on the pre-clinical
      study of drug-eluting coronary stent system, the basic requirement of the
      authorized administration was summarized to help manufacture prepare the document
      during the registration process.

PMID- 25980144
TI  - [Discussion to the advanced application of scripting in RayStation TPS system].
AB  - In this study, the implementation methods for the several functions are explored
      on RayStation 4.0 Platform. Those functions are passing the information such as
      ROI names to a plan prescription Word file. passing the file to RayStation for
      plan evaluation; passing the evaluation result to form an evaluated report file.
      The result shows the RayStation scripts can exchange data with Word, as well as
      control the running of Word and the content of a Word file. Consequently, it's
      feasible for scripts to inactive with third party softwares upgrade the
      performance of RayStation itself.

PMID- 25980145
TI  - [An artifact troubleshooting for GE PROFILE 0.2 T MR].
AB  - According to many years of MR experience for maintenance, Through careful
      observations artifacts, according to the easy first principle, use the process of
      elimination, first check the external environment to the interior of the machine,
      the layers of delivery in the cause of failure, eliminate the artifact.

PMID- 25980146
TI  - [The quantification and significance of muscle segment homeobox gene Msx2, human
      topoisomerase II-alpha, HPV16 and VEGF in sinonasal inverted papilloma].
AB  - OBJECTIVE: To investigate the quantification and significance of Msx2, topoII
      alpha; HPV16 and VEGF in sinonasal inverted papilloma(SNIP), to study the
      correlation among the four factors,and to discover the relationship between Msx2
      and topoII-alpha in the process of SNIP malignant transfomation. METHOD: Real
      time quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect the
      expression of Msx2, topoII-alpha, HPV16 and VEGF in 13 cases of sinonasal
      inverted papilloma (SNIP), 10 cases of sinonasal squamous cell carcinoma(NSCC)
      and 10 cases of inflammatory nasal polyp paraffin (INP)tissues. According to the
      pathology results SNIP were divided into mild dysplasia, moderate dysplasia and
      severe dysplasia. All the data were analysised by SPSS17. 0, P<0. 05 was refered
      to statistically significant difference. RESULT: The mRNA level of Msx2, topoII
      alpha, VEGF and HPV16 in SNIP, NSCC tissues were significantly higher than in the
      INP tissues (P<0. 05). The expression differences of Msx2, topoII-alpha, HPV16
      and VEGF mRNA level in SNIP tissues which were divided into three groups
      according to their pathological results,were all statistically significantly
      different between any two of the three groups (P< 0. 05). Using Pearson
      correlation coefficient analysis,we found positive correlation between any two of
      the mRNA level of Msx2, topoII-alpha, VEGF and HPV16 (P<0. 05). CONCLUSION: Msx2
      and topoII-alpha may play an important role in the process of SNIP Malignant
      transformation,which may be new targets for gene therapy of SNIP and NSCC.

PMID- 25980147
TI  - [Significances of COX-2, p21, Ki-67 expression and HPV infection in nasal
      inverted papilloma].
AB  - OBJECTIVE: To investigate the significance of expression of COX-2, p21, Ki67 and
      HPV in nasal inverted papilloma. METHOD: Detecting COX-2, p21, Ki-67 in 30 cases
      of nasal inverted papilloma (NIP), 20 cases of nasal polyps (NP) and 10 cases of
      normal nasal mucosa (NM) by two step immunohistochemical method, and HPV virus by
      flow-through hybridization method. RESULT: The positive expression rate of COX-2
      and Ki-67 in NIP, NP and NM group was decreased in turn, COX-2 had significant
      difference in the groups(chi2 = 30.00, P< 0. 05); the positive expression rate of
      Ki-67 had significant differences between NIP and NM group (chi2 = 8. 533, P<0.
      05). The expression of COX-2 in NIP tissues was positively correlate with that of
      Ki-67 by using Spearman rank correlation analysis (r=0.78, P<0.05). Expression of
      p21 were not observed in NIP group. The positive rate of HPV was 26. 67% in 30
      cases of NIP, all of HPV16 type. CONCLUSION: COX-2, Ki-67 and HPV infection have
      certain correlation with the occurrence of NIP. The occurrence of NIP has
      relationship with inflammatory reaction mediated by COX-2. Ki-67 can well reflect
      the proliferation activity of tumor cells, and can be used to measure the
      proliferation rate of nasal inverted papilloma. The COX-2 and Ki-67 have a
      synergistic role in the pathogenesis of NIP. p21 has no significant relationship
      with the incidence of NIP. HPV infection is related to the pathogenesis of NIP,
      but not as a;major factor in the pathogenesis of NIP.

PMID- 25980148
TI  - [Short term evaluation of quality of life in patients with chronic rhinosinhsitis
      by using Chinese version of the inonasal outcome test-22].
AB  - OBJECTIVE: To evaluate short term quality of life of patients with chronic
      rhinosinusitis by using Chinese version of the sinonasal outcome test-22 (SNOT
      22) and to formulate an ideal therapy system for patients with chronic
      rhinosinusitis. METHOD: Using prospective randomized controlled design,we chose
      the SNOT-22 to evaluate and compare 78 CRS patients' quality of life (QOL) before
      surgery, at 1-month,3-month, 6-month and 9-month after functional endoscopic
      sinus surgery(FESS). At the same time, we randomly chose 100 healthy controls to
      compare their QOL with those of CRS patients after FESS. RESULT: We found that
      except for 5 items (cough, ear expanding, otalgia, facail pain and weary ), the
      grade of 17 other items of CRS patients were significantly higher than those of
      the healthy controls (P<0. 05). There was no significant difference in 7 items
      (olfactory sensation, hypogeusis, backflow of nasal discharge, difficult to fall
      asleep, bad sleep, bad work efficiency, depression, embarrassment ) at 3 months
      after FESS between chronic rhinosinusitis patients and healthy controls (P>0.
      05). There was no significant difference in 9 items (blow noses, sneeze,
      rhinorrhea, nasal discharge thickness, dizziness, night wake, tired of wake,
      attention deficit, sense of loss) at 6 months after FESS between chronic
      rhinosinusitis patients and healthy controls (P>0. 05). There was no significant
      difference in nasal obstruction at 6 months after FESS between chronic
      rhinosinusitis patients and healthy controls (P>0.05), at this time the totle
      grade was normal (P>0. 05). The recovery period of QOL in patients was about 9
      months (P>0. 05). The 5 great items were nasal obstruction, olfactory sensation,
      hypogeusis, nasal discharge, nasal discharge thickness and blow noses. There was
      no difference in items except for bad sleep replacing nasal discharge thickness
      between 1-month and 9-month after surgery. CONCLUSION: The Chinese vesion of SNOT
      22 could evaluate QOL of CRS patients in this area. The recovery of QOL of CRS
      patients needs about 6 months after FESS, but problems of olfactory sensation,
      hypogeusis, nasal discharge and difficult to sleeep still needs to be resolved.

PMID- 25980149
TI  - [Clinical observation of preoperative anxiety and postoperative pain after
      endoscopic sinus surgery].
AB  - OBJECTIVE: To investigate the correlation of preoperative anxiety and
      postoperative pain after endoscopic sinus surgery in chronic rhinosinusitis (CRS)
      with or without nasal polyps (CRSwNP or CRSsNP). METHOD: Subjects were 167 adults
      scheduled for functional endoscopic sinus surgery(FESS),in our hospital.
      preoperative issuing State-Trait Anxiety Inventory(STAI), carried anxiety scores.
      8 h, 32 h, 56 h after surgery, recorded the pain score of Wong-Banker facial
      scale method (FPS-R). Analysed the correlation between preoperative anxiety score
      and the degree of postoperative pain. RESULT: Patients'preoperative S-AI mean
      score was 42. 45 +/- 9. 98, T-AI mean score was 41. 81+/-8. 47. The mean pain
      score in patients 8 h after surgery was 6. 33+/-1. 74,32 h was 4.21+/-1.51, 56 h
      was 2.35+/-1.42. In the 8 h group postoperative pain were 0 cases with no pain,
      10 cases of mild pain, moderate pain in 107 cases, 47 cases of severe pain, sharp
      pain in three cases. After 32 hours 9 cases with no pain, 97 cases of mild pain,
      moderate pain in 32 cases, 29 cases of severe pain, no sharp pain patients. 56
      hours after surgery, there were 108 cases with no pain, mild pain in 44 cases, 15
      cases of moderate pain. Preoperative S-AI and T-AI score and 8 h, 32 h, 56 h
      after surgery pain score had no significant correlation. CONCLUSION: The pain of
      patients within 8 h after FESS is most evident,with the passage of time, the
      degree of pain gradually reduced. Preoperative anxiety and postoperative pain
      have no significant correlation.

PMID- 25980150
TI  - [Application of nasopore and budesonide suspension on tamping after endoscopic
      sinus surgery].
AB  - OBJECTIVE: To investigate the clinical effect of nasal packing of pulmicort
      respules combined withnasopore after endoscopic sinus surgery. METHOD: A total of
      30 CRSwNP and CRSsNP patients with bilateral functional endoscopic sinus surgery
      and finished following up visit were randomly choosed, conventionally select the
      left nasal cavity as the experimental group, the right nasal cavity as the
      control group. Experimental group to pack the nasal cavity with pulmicort
      respules union nasopore after surgery and control group to pack the nasal cavity
      with only nasopore after surgery. The differences were observed in patients with
      subjective symptoms and recovery of mucosa of operative cavity between the two
      groups after two weeks, one month and three months. RESULT: (1) The postoperative
      VAS symptoms score about nasal obstruction, nasal secretion, headache, dizziness
      and distending pain after two weeks,one month and three months in the experiment
      group were significantly better than those in the control group(P<0.05). (2) The
      postoperative Lund-Kennedy endoscopic mucosa morphology score after two weeks,
      one month and three months in the experiment group were significantly better than
      those in the control group(P<0.05); (3) After three months, the experiment group
      had 28 cases with clinic symptoms cured(93. 3%), Total effective rate was 96. 6%;
      The control group had 22 cases with clinic symptoms cured (73. 3%), total
      effective rate was 93. 3%. The cure rate of the experiment group was
      significantly higher than the control group(P<0.05), but there was no statistic
      difference between the two groups in the total effective rate (P>0.05).
      CONCLUSION: The application of nasal packing of pulmicort respules combined with
      nasopore after functional endoscopic sinus surgery can effectively relieve
      postoperative uncomfortable symptoms, promote recovery of mucosa of perative
      cavity, which deserves clinical promotion.

PMID- 25980151
TI  - [Research on 3-D reconstruction of sphenoid sinus in children and adolescents in
      Yunnan region].
AB  - OBJECTIVE: To research the correlation between development of sphenoid sinus and
      age in normal children and adolescents by 3-D CT images. METHOD: Review of CT
      images of the skulls of 120 children and adolescents aged 0~20 years old. They
      were divided into five groups. Then reconstructed 3-D shape of the sphenoid
      sinus, and measureed the maximal anteroposterior diameter, longitudinal diameter,
      and transverse diameter of the bilateral sphenoid sinus by the 2-D and 3-D
      approach respectively, then process statistical analysis. RESULT: Pearson
      analyses revealed a positive correlation between various diameters of sphenoid
      sinus measured by 2-D and 3-D approach and age (P<0. 05). CONCLUSION: The
      development of sphenoid sinus has a linear correlation with age, and increases
      with age and growth in Yunnan region. It helps to know the three-dimensional CT
      images of the sphenoid sinus in children and adolescents by Simplant software,
      thereby allow the clinicians to understand the current situation of the
      development of sphenoid sinus. Meanwhile, it contributes to preoperative
      evaluation of sinus problems.

PMID- 25980152
TI  - [Clinal analysis of 202 nasal bone fractures cases].
AB  - OBJECTIVE: To evaluate the age, sex, etiology, diagnosis and treatment time of
      nasal bone fractures. METHOD: Clinical data of 202 cases with nasal bone
      fractures treated in the hospital were retrospectively analysed. RESULT: A total
      of 202 cases,163 men (80. 7%) and 39 women (19. 3%). Fifty-two patients had a
      relationship with alcohol consumption, and all of them were males. The most
      frequent reasons of the injury were fight 46. 5% (94 cases) followed by falling
      down 21. 3% (43 cases), traffic accidents 19. 3% (39 cases), works related 6. 5%
      (13 cases), sport injuries 5. 9% (12 cases) and others 0. 5% (1 cases). Patients
      distribution in seasons were: spring 54 cases (26.7%), summer 42 cases (20.8%),
      autumn 58 cases (28.7%), winter 48 cases (23. 8%). Diagnosis of nasal bone
      fractures were made positively by x-ray films in 79. 7% of cases, but 100% by CT.
      Positive predictive value of CT was superior to that of X-ray films in the
      diagnosis of nasal bone fracture. CONCLUSION: High morbidity of nasal bone
      fracture was seen in the age group of 20-29 years, and predominantly in male.
      Fight was found to be the main etiologic factor. We think that CT is necessary
      for diagnosing nasal bone fracture.

PMID- 25980153
TI  - [Ultimobranchial fistula and cyst of thyroid:4 cases report and review of
      literature].
AB  - OBJECTIVE: To investigate the clinical feature,diagnostic and therapeutic methods
      of ultimobranchial fistula and cyst of thyroid. METHOD: Four cases of
      ultimobranchial fistula and cyst of thyroid in our hospital were reported and the
      relevant literatures were reviewed. RESULT: The branchial fistula and cyst of
      four cases were adhered to thyroid,with unclear anatomical landmarks, the
      function of recurrent laryngeal nerve were bad before the operation in two cases.
      The nerve of four cases were retained, the function of thyriod and parathyroid
      gland were normal and no recurrence were found. CONCLUSION: Ultimobranchial
      fistula and cyst of thyroid is rare and is easier to be misdiagnosed and wrong
      treated. Surgical excision is effective for it and recurrent laryngeal nerve
      should be protected when performing the operation.

PMID- 25980154
TI  - [Juvenile onset respiratory papillomatosis: risk factors for severity].
AB  - OBJECTIVE: This study was designed to explore the risk factors associated with
      severity of juvenile onset recurrent respiratory papillomatosis. METHOD: A
      retrospective study was conducted to study determinants of severe forms of
      juvenile recurrent onset respiratory papillomatosis. The patients were separated
      into different groups based on the onset age, the first recurrence of age, the
      first recurrence of period, gender and incision of tracheal respectively. The
      relationship among the lesion severity score,the involvement of the subregion,
      operation period and the next operation period were also explored. RESULT: It was
      observed that some children who recurred before 4 years old required more
      surgery, shorter operation period(the average, longest or shortest operation
      period) than those elder children, the differences were statistically (P=0. 029,
      0. 003, 0. 010, 0. 039, respectively). The severity score of lesion was
      correlated positively with the involvement of the subregion and negatively with
      operation period (r=0. 914, -0. 451, respectively). Some children who diagnosed
      before 4 years old had to endure more severity score and shorter operation period
      than those older children, the differences were statistically (P= 0. 036, 0. 000,
      respectively). 8 cases accepted incision of tracheal, they accepted more surgery
      too. But the differences in the onset age, the first recurrence of age, and the
      operation period were not statistically. CONCLUSION: The results showed that the
      clinical course of juvenile onset recurrent respiratory papillomatosis was
      closely related to the first recurrence age and period, while the severity of
      disease was associated to the onset age and the involvement of the subregion.

PMID- 25980155
TI  - [Clinical analysis of 14 cases with nasal respiratory enithelial adenomatoid
      hamartom].
AB  - OBJECTIVE: To describe and analyze the clinical features of nasal respiratory
      epithelial adenomatoid hamartom and improve the levels of diagnosis and
      treatment. METHOD: Fourteen cases of nasal respiratory epithelial adenomatoid
      hamartom confirmed by pathology were collected and analyzed. RESULT: In 14 cases,
      primary complaint of Hyposmia(or Anosmia)and nasal obstruction were occured in 13
      and 11 cases respectively. Four cases had past history of endoscopic sinus
      surgery because of the diagnosis of nasal polyps. Polypoid neoplasms could be
      seen in the bilateral olfactory clefts. Sinus CT showed soft tissue shadows in
      bilateral nasal cavity and mucous membrane thickening in different sinus.
      Endoscopic sinus surgery were utilized to eliminate focus in all cases. All cases
      weren t recurred after 2-20 months' following-up visitings. CONCLUSION: Nasal
      respiratory epithelial adenomatoid hamartom is so rare that clinical and
      pathological doctors have limited knowledge of it. It has its own characteristics
      from the clinical symptoms, signs to sinus CT although they are nonspecific. So
      we should improve the understanding about it to avoid misdiagnosis or missed
      diagnosis.

PMID- 25980156
TI  - [Treatment outcome and prognosis of head and neck hemangiopericytoma].
AB  - OBJECTIVE: Aim of the study is to report the unique clinicopathologic feature,
      treatment outcome and prognostic factors of head and neck hemangiopericytoma
      (HNHPC). METHOD: A retrospective data collection of reported HNHPC cases, in
      which therapy, follow-up and outcome data were available, was performed from the
      electronic database of PubMed, Embase, Google scholar, China National Knowledge
      Infrastructure, Wan Fang and Wei Pu until on December 31, 2013. RESULT: A total
      of 213 HNHPC cases were identified from 122 peer-reviewed articles. The
      recurrence rate was 24.4% (51/209). The positive surgical margin (OR= 3. 977,
      P<0. 01) and poor pathologic differentiation (OR=l. 890, P<0. 01) were associated
      with increased local recurrence. The metastasis rate was 15.8% (22/139). The
      positive surgical margin (OR=13. 833, P<0. 01), poor pathologic differentiation
      (OR=4. 661, P<0. 01) and non-surgical treatment (OR=2. 000, P<0. 01) were
      associated with increased distant metastasis. The mortality rate was 15. 0%
      (32/213). The tumor size >5. 0 cm in diameter (OR= 2. 860, P<0. 05), positive
      surgical margin (OR=9. 833, P<0. 01), poor pathologic differentiation (OR=4. 061,
      P<0. 01) and non-surgical treatment (OR=2. 032, P<0. 01) were associated with
      worse mortality. The treatment included surgery alone 139 cases, multiple
      treatments 64 cases and non-surgical treatment 10 cases. The overall survival
      (OS) of the 213 cases was 85%, and the 3-year, 5-year and 10-year OS were 86%,
      78% and 74%, respectively. The 3-year, 5-year and 10-year OS for surgery alone
      were 95%, 88% and 84%, respectively. The 3- year, 5-year and 10-year OS for
      surgery plus radiotherapy were 90%, 80% and 80%, respectively. The 3-year, 5-
      year and 10-year OS for surgery plus chemotherapy were 75%, 25% and 25%,
      respectively. The 3-year, 5-year and 10-year OS for surgery plus radio
      chemotherapy were 67%, 58% and 46%, respectively. There were signifi- cant
      survival difference in recurrence-free survival (RFS), metastasis free survival
      (MFS) and OS depending on surgical margins (P<0. 01). RFS, MFS and OS difference
      were identified depending on pathologic differentiation (P<0. 01). MFS and OS
      differences were observed on the different treatment modality (P<0. 01). OS
      differences was observed on the different tumor sizes (P<0. 05). Positive
      surgical margins was correlated with disease recurrence (HR= 3. 680, P<0.01),
      while poor pathologic differentiation was correlated with metastasis and death
      (HR=2. 619, P<0. 05 and HR=3. 188, P<0. 05). The tumor size >5. 0 cm in diameter
      and non-surgical treatment was correlated with death (HR= 5. 461, P<0. 01 and HR=
      8. 563, P<0. 01, respectively). CONCLUSION: The surgical resection was the
      mainstream treatment and it was superior to multiple treatments. The tumor size,
      surgical margins, pathological differentiation and non-surgical treatment were
      independent prognostic factors.

PMID- 25980157
TI  - [The study of the correlation of middle meatus volume and maxillary fungal ball].
AB  - OBJECTIVE: Observing the anatomic variation and measuring the bone volume of
      meatus and nasal cavity by analyzing the expression of paranasal sinus CT.
      Searching whether these variation and volume data are related to maxillary fungal
      ball. METHOD: Measuring the double side bone volume of middle meatus,nasal cavity
      and the rate of middle meatus volume in the same side of nasal cavity
      respectively in the normal group, the maxillary fungal ball group. Observing the
      anatomic variation and statistically evaluating the anatomic variation and volume
      of nasal cavity and nasal meatus. RESULT: In the maxillary fungal ball group, the
      affected side and the contralateral side volume of middle meatus,nasal cavity and
      the rate of middle meatus volume in the nasal cavity had no statistical
      difference (P>0.05); Comparing the middle meatus volume and the rate of middle
      meatus of the maxillary fungus ball group affected side and normal group,there
      was statistical difference (P<0. 05). In the maxillary fungal ball group and the
      normal group, the morbidity of deviation septum were 24. 24% and 33. 33%, the
      morbidity of OMC variation were 30. 3% and 26. 67% (P<0.05), the morbidity of
      nasal anatomic variation were 54. 55% and 60.00%, there was no statistical
      difference (P>0.05). CONCLUSION: Maybe there is a correlation between the
      enlarged bone middle meatus and the maxillary fungal ball. There is no
      relationship between the nasal anatomic variation and the maxillary fungal ball.

PMID- 25980158
TI  - [Radiographic study of maxillary sinus associated with molars in adult].
AB  - OBJECTIVE: to explore the relationship between the maxillary sinus volume and the
      amount of alveolar bone, and the effect of molar loss upon the maxillary sinus
      was further analyzed,by measuring adult maxillary sinus volume, sinus ridge
      distance, and calculating the gasification coefficient of maxillary sinus.
      METHOD: One hundred and ninety cases (361 maxillary sinus) with CT examinations
      were collected, they were divided into group A and group B, 121 cases (242
      maxillary sinus) of normal subjects served as group A, 42 cases (65 maxillary
      sinus) with molar part off were B group, in which 31 maxillary sinus with a molar
      loss were group B1,22 maxillary sinus with two molar loss were B2 group,12
      maxillary sinus with three molar loss (one molar remains) were B3 group, 27 cases
      (54 maxillary sinus) with upper teeth off were C group. Bymeasureing the
      maxillary sinus volume, sinus ridge distance and the size of the maxillary sinus,
      calculating the gasification coefficient, we analyzed the relationship between
      maxillary volume and sinus ridge distance, and comparatively analyzed the
      differences among the three groups in the size, gasification coefficient, volume
      of maxillary sinus and sinus ridge distance. RESULT: In the normal group,the
      volume of maxillary sinus and sinus ridge distance had a correlation coefficient
      of -0. 63,(P< 0.05); Sinus ridge distance in group A was larger than the other
      two groups (P<0.05), and larger in B group than in C group (P<0. 05),
      anteroposterior maxillary sinus diameter and reft-right diameter in C group was
      greater than in A group and B group(P<0.05), group C gasification coeffiecent was
      less than A group and B group (P<0. 05). CONCLUSION: The volume of maxillary
      sinus is negatively correlated with the amont of alveolar bone; Upper teeth's
      shedding promotes maxillary sinus deformation; Maxiuary sinus volume has a
      tendency to decrease.

PMID- 25980159
TI  - [Clinical analysis of diagnosis and treatment on retro-esophageal space abscess].
AB  - OBJECTIVE: To explore the clinical manifestations and treatments of retro
      esophageal space abscess. METHOD: The clinical data of 27 cases with retro
      esophageal space abscess were analyzed retrospectively. Twenty-one cases (77.
      78%) were secondary to acute injury of esophageal meatus caused by foreign
      bodies. 2 cases (7. 41%)were secondary to old foreign body infection in retro
      esophageal space, 3 cases (11. 11%) after secondary to pharyngeal abscess, and 1
      case (3. 70%) was unknown to etiology. All patients were confirmed by sectional
      medicalimageology. Six cases(Conservation group, C group) were treated
      conservatively and 6 cases (Oropharyngeal incision group, OI group) were
      performed with oropharyngeal incision drainage. 15 cases(Extra-neck incision
      group, ENI group)were performed with extra-neck incision and vacuum sealing
      drainage. RESULT: In C group, 6 cases were cured with conservative therapy and
      the average hospital stay was 15. 6 days. In OI group, 5 cases were healed with
      oropharyngeal drainage but aspiration pneumonia complicated with septic shock
      occurred in 2 cases, and 1 case dead from septic shock secondary to mediastinum
      and lung abscess. The average hospital stay was 18. 8 days. In ENI group, 15
      patients were cured with extra-neck drainage without complication and the average
      hospital stay was 9. 5 days. CONCLUSION: The main causes of retro-esophageal
      space abscess are foreign body injury of upper esophagus and remnant of retro
      esophageal space. Sectional medicalimageology can be of important value of
      diagnosis and treatment for displaying the retro-esophageal space abscess and
      other deep cervical fascia space sufficiently. Incision and vacuum sealing
      drainage via extra-neck is an effective therapy while oropharyngeal drainage is
      less effective and is not advocated as a primary treatment because of aspiration
      pneumonia complication . Conservative cure is a choice for patients without
      dyspnoea and background diseases, and it is necessary to recognize and treat
      severe complications early.

PMID- 25980160
TI  - [Clinical observation of the adverse effects of standardized dust mite allergen
      preparation in the treatment of allergic rhinitis].
AB  - OBJECTIVE: To observe the adverse effects of specific immunotherapy (SIT) with
      standardized dust mite allergen preparation in the treatment of allergic
      rhinitis. METHOD: Three hundred and eighty-six patients with allergic rhinitis
      who received subcutaneous SIT with a standardized dust mite allergen preparation
      were enrolled in this study. The patients were treated for at least 15
      weeks,adverse effects after each injection from dosing phase to maintenance phase
      were recorded and incidence of adverse effects were analyzed. RESULT: Of all the
      patients,adverse reactions occurred in 42 patients (10. 9%),10 local reactions
      (2. 6%) and 36 systemic side effects (9. 3%) which included 34 mild ,1 moderate
      and 1 severe side effects (no fatal) were reported respectively. None had
      anaphylactic shock. Among three treatment options, incidence of routine program
      was the highest (21.1%),followed by adult cluster program (11. 9%), adverse
      effects of children cluster program was the least (1. 5%). The adverse effects
      often happened in the middle and late phase of does addition period and early
      phase of maintenance period. CONCLUSION: SIT with standardized dust mite allergen
      preparation in the treatment of allergic rhinitis is a safe and effective
      treatment by complying with the guidelines and taking specific interventions.

PMID- 25980161
TI  - [Influence of different thyroidectomy on perioperative blood calcium
      concentration].
AB  - OBJECTIVE: lo discuss the inmtluence of different thyroidectomy on perioperative
      blood calcium concentration. METHOD: Total number of patients was 240. These
      patients of thyroid tumors were recruited. Clinical and follow-up datum were
      retrospective analyzed. RESULT: Patients were divided into four groups by
      different operative methods. Group one was patients taken one-side thyroidectomy,
      group two taken one-side lymph node dissection plus, group three taken two-sides
      thyroidectomy,and group four taken one or two sides lymph node dissection plus.
      Group two was easier to become hypocalcemia and their calcium concentration
      decreased more remarkably, compared with group one. Patients taken two-sides
      thyroidectomy had the familiar outcome. CONCLUSION: Patients taken lymph node
      dissection were easier to become hypocalcemia, compared with patients only taken
      thyroidectomy.

PMID- 25980162
TI  - [The clinic experience and literature review with 1 case of chronic
      tracheoesophageal fistula].
AB  - OBJECTIVE: To investigate the clinical features of chronic tracheoesophageal
      fistula (TEF), provided disease-related treatment experience and lessons for
      clinicians. METHOD: To successfully repair one case of chronic tracheoesophageal
      fistula with surgery, and to analyze the clinical treatment process, combined
      with relevant literature, the author reported the experiene of diagnosis and
      treatment in TEF. RESULT: After the gastrointestinal ostomy and Stent
      implantation, the fistula persisted, nine months later ,we took the surgery to
      repair the fistule, ten days postoperation, the fistule healed and esophageal
      iodine water examination didn't prompt obvious abnormalities, the patient was
      discharged without any postoperative complications 12 days postoperation.
      CONCLUSION: If conservative treatment failed with TEF, the surgical repair should
      be carried timely, By double sutured with fistula in surgery, and reinforced with
      the approaching muscle tissue, It can achieve good results.

PMID- 25980163
TI  - [The effect of hypertonic seawater and isotonic seawater for nasal mucosa of
      allergic rhinitis mice model].
AB  - OBJECTIVE: To study the effect of hypertonic seawater and isotonic seawater for
      nasal mucosa of allergic rhinitis mice model, and explore the possible mechanism
      of nasal irrigation with seawater in treatment of allergic rhinitis. METHOD: We
      used Der pl to make allergic rhinitis model of BALB/c mice, and divided them into
      three groups randomly. Nasal irrigation with hypertonic seawater (HS) or isotonic
      seawater (IS) in the treatment group 1-14 days after modeling, and black control
      (BC) group was given no treatment after modeling. Normal control (NC) group was
      given no treatment, the number of rubs and sneezings in each group were counted
      in 30 min after the last nasal irrigation. Mice were then killed 24 h after the
      last therapy. The noses of mice from each group were removed and fixed, then the
      slices were stained with hematoxylin and eosin, the others were observed by
      transmission electron microscope. RESULT: Mice with hypertonic seawater and
      isotonic seawater were significantly improved in rubs and sneezings compared to
      the black control group (P<0. 05); The number of eosinophiles in mucosal tissues
      of HS group and IS group had no significant difference with that of the black
      control group (P> 0. 05); Ciliated columnar epithelium cells in mucosal tissues
      of HS group and IS group were arranged trimly, better than that in the black
      control group. Morphology and microstructure in nasal mucosal of HS group was
      closer to the normal group than in IS group. CONCLUSION: The injury of nasal
      mucosa ciliated epithelium was significantly improved by nasal irrigation with
      hypertonic seawater and isotonic seawater, and the former is better than the
      latter, the mechanism of nasal irrigation with seawater in treatment of allergic
      rhinitis may rely on repairing the injured nasal mucosa ciliated epithelium,
      thereby the symptoms of nasal was reduced.

PMID- 25980164
TI  - [Effect of micro-ecological environment on incidence of allergic rhinitis on
      mice].
AB  - OBJECTIVE: This study was designed to find out the impact of micro-ecological
      environment on the incidence of allergic rhinitis after developing a model of
      allergic rhinitis on mice. METHOD: Sixty mice were randomly divided into GF group
      (n=30) and SPF group (n=30). Mice of GF group were fed in the germ-free
      environment and mice of SPF group were fed in the specific pathogen-free
      environment. Then each group were randomly divided into model group (20 mice) and
      control group (10 mice). Establish allergic rhinitis model in the mice of model
      group using ovalbumin (OVA) at the age of 6 weeks, observe and score the
      corresponding symptoms and signs that could been induced. Stain with hematoxylin
      eosin (HE) staining method for nasal mucosa to observe the morphological changes.
      Using enzyme linked immunosorbent assay to detect the concentration of IgE, IFN
      gamma and IL-4 in the peripheral blood serum. RESULT: The chi square test showed
      that the incidence of allergic rhinithis in the mice of GF group was
      significantly higher than that in the SPF group (P< 0. 05). HE staining showed
      that the nasal mucosas of allergic rhinitis positive reaction mice were highly
      congestive and edematous and had a large number of inflammatory cell
      infiltration, while there was no abnormal morphology of nasal mucosas in mice
      with no allergic rhinitis reaction. EOS counting displayed that the number of
      eosinophilic cells in nasal mucosa of positive allergic rhinitis reaction mice
      was increased significantly. The concentration of IgE and IL-4 in the serum of
      positive allergic rhinitis reaction mice was highly increased (P <0. 05), and IFN
      gamma was significantly decreased (P< 0.05). CONCLUSION: The difference of micro
      ecological environment may play a key role in the occurrence of allergic rhinitis
      in mice.

PMID- 25980165
TI  - [Integrated traditional Chinese and Western medicine clinical research for the
      treatment of allergic rhinitis in children].

PMID- 25980166
TI  - [Endoscopic surgery for sphenoidal and ethmoidal cysts that impair orbit:report
      of 13 cases].

PMID- 25980167
TI  - [Treatment of difficult laryngeal exposure during suspension microlaryngoscopy].

PMID- 25980168
TI  - [Low-temperature coblation tonsillectomy after peritonsillar abscess].

PMID- 25980169
TI  - [Prevention of tracheostomal stenosis following total laryngectomy using a middle
      incision of trachea tracheostomy: report of 35 cases].

PMID- 25980170
TI  - [1 case of vocal cord plexiform schwannoma].
AB  - Summary A 36 years old patient with hoarseness for 2 years and got worsen for one
      month, electronic laryngoscopy showed a red smooth-faced wide based neoplasm on
      the posterior 2/3 of the right side of the vocal cords. The neoplasm was excised
      under suspension laryngoscope . The pathologic results showed:Cells were weave
      patterned, infiltrative growth, mitotic figure was rare. Immunohistochemical
      results showed CD34 (-), SMA (-), DM (-), S - 100 (+). The pathological diagnosis
      was plexiform schwannoma.

PMID- 25980171
TI  - [Bilateral nasal vestibular cyst 1 case].
AB  - Patients with bilateral nasal vestibule area swelling of 1 week, no obvious pain
      and symptoms of nasal congestion, bilateral nasal vestibule area was highly
      uplifted, nostril was significantly smaller, both sides existed a palpable 2. 0
      cm * 2. 2 cm and 2. 0 cm * 2. 0 cm cystic mass. Ultrasound showed both sides of
      the nasal bonehad cystic lesions. Sinus CT showed local quasicircular soft tissue
      shadow at the bottom of bilateral piriform aperture. The postoperative pathology
      report: the cystiform tissue is covered with squamous epithelium, infiltration of
      inflammatory cells could be seen and is consistent with the diagnosis of
      bilateral nasalvestibular cyst.

PMID- 25980172
TI  - [Hard palate fistula and nasal septum perforation after leukemia infection:
      report of one case].
AB  - Most of palatal fistula occur from poor repairation of cleft palate, leaving an
      abnormal channel between mouth and nose. Palatal fistula can cause a series of
      complications, such as voice and hearing disorder, poor oral and nasal hygiene,
      psychological diseases and so on. However, hard palate fistula secondary to
      Leukemia infection is rarely seen, it hasn't been reported yet. We report one
      case with hard palate fistula and nasal septum perforation after Leukemia
      infection.

PMID- 25980173
TI  - [Prediction of the original location of sinonasal inverted papilloma by
      preoperative imaging].
AB  - Sinonasal inverted papilloma (SNIP) is one of the most common benign sinonasal
      tumors demonstrating a high recurrence rate after surgery, and sometimes presents
      malignant tendency or coexists squamous cell carcinoma. Therefore, it is
      essential to achieve complete surgical resection, especially the original
      location of SNIP. In this paper, we evaluated the predictability of preoperative
      CT and magnetic resonance imaging (MRI) for localization of SNIP origin.

PMID- 25980174
TI  - [The progress of nasal endoscopic surgery with imaging-guided system].
AB  - The aim of this paper is to introduce state-of-the-art endoscopic surgery with
      imaging-guided system in terms of indication, preoperative registration and
      intraoperative imaging and to describe future development trend.

PMID- 25980175
TI  - Bottleneck limitations for microRNA-based therapeutics from bench to the bedside.
AB  - MicroRNAs are endogenous non-coding small RNAs that repress expression of a broad
      array of target genes. Research into the role and underlying molecular events of
      microRNAs in disease processes and the potential of microRNAs as drug targets has
      expanded rapidly. Significant advances have been made in identifying the
      associations of microRNAs with cancers, viral infections, immune diseases,
      cardiovascular diseases, wound healing, biological development and other areas of
      medicine. However, because of intense competition and financial risks, there is a
      series of stringent criteria and conditions that must be met before microRNA
      based therapeutics could be pursued as new drug candidates. In this review, we
      specifically emphasized the obstacles for bench-based microRNA to the bedside,
      including common barriers in basic research, application limitations while moving
      to the clinic at the aspects of vector delivery, off-target effects, toxicity
      mediation, immunological activation and dosage determination, which should be
      overcome before microRNA-based therapeutics take their place in the clinic.

PMID- 25980176
TI  - Solid lipid nanoparticles containing copaiba oil and allantoin: development and
      role of nanoencapsulation on the antifungal activity.
AB  - The aim of this work was to develop solid lipid nanoparticles (SLN) containing
      copaiba oil with and without allantoin (NCOA, NCO, respectively) and to evaluate
      their antifungal activity. Nanoparticle suspensions were prepared using a high
      homogenisation technique and characterised by dynamic light scattering, laser
      diffraction, nanoparticle tracking analysis, multiple light scattering analysis,
      high-pressure liquid chromatography, pH and rheology. The antifungal activities
      of the formulations were tested in vitro against the emergent yeasts Candida
      krusei and Candida parapsilosis, and the fungal pathogens of human skin
      Trichophyton rubrum and Microsporum canis. The dynamic light scattering analysis
      showed z-average diameters (intensity) between 118.63 +/- 8.89 nm for the
      nanoparticles with both copaiba oil and allantoin and 126.06 +/- 9.84nm for the
      nanoparticles with just copaiba oil. The D[4,3] determined by laser diffraction
      showed similar results of 123 +/- 1.73 nm for the nanoparticles with copaiba oil
      and allantoin and 130 +/- 3.6 nm for the nanoparticles with copaiba oil alone.
      Nanoparticle tracking analysis demonstrated that both suspensions had monomodal
      profiles and consequently, the nanoparticle populations were homogeneous. This
      analysis also corroborated the results of dynamic light scattering and laser
      diffraction, exhibiting a smaller mean diameter for the nanoparticles with
      copaiba oil and allantoin (143 nm) than for the nanoparticles with copaiba oil
      (204 nm). The physicochemical properties indicated that the dispersions were
      stable overtime. Rheology evidenced Newtonian behaviour for both suspensions.
      Antifungal susceptibility showed a MIC90 of 125 MUg/mL (nanoparticles with
      copaiba oil) and 7.8 MUg/mL (nanoparticles with copaiba oil and allantoin)
      against C. parapsilosis. The nanoparticles with copaiba oil and the nanoparticles
      with copaiba oil and allantoin presented a MIC90 of 500 MUg/mL and 250 MUg/mL,
      respectively, against C. krusei. The MIC90 values were 500 MUg/mL (nanoparticles
      with copaiba oil) and 1.95 MUg/mL (nanoparticles with copaiba oil and allantoin)
      against T. rubrum. Against M. canis, the nanoparticles with copaiba oil and
      allantoin had a MIC9 of 1.95 MUg/mL. In conclusion, nanoencapsulation improved
      the antifungal activity of copaiba oil, which was enhanced by the presence of
      allantoin. The MICs obtained are comparable to those of commercial products and
      can represent promising therapeutics for cutaneous infections caused by yeasts
      and dermatophytes.

PMID- 25980177
TI  - D-Optimal mixture experimental design for stealth biodegradable crosslinked
      docetaxel-loaded poly-epsilon-caprolactone nanoparticles manufactured by
      dispersion polymerization.
AB  - We report here our efforts on the development of stealth biodegradable
      crosslinked poly-epsilon-caprolactone nanoparticles by free radical dispersion
      polymerization suitable for the delivery of bioactive agents. The uniqueness of
      the dispersion polymerization technique is that it is surfactant free, thereby
      obviating the problems known to be associated with the use of surfactants in the
      fabrication of nanoparticles for biomedical applications. Aided by a statistical
      software for experimental design and analysis, we used D-optimal mixture
      statistical experimental design to generate thirty batches of nanoparticles
      prepared by varying the proportion of the components (poly-epsilon-caprolactone
      macromonomer, crosslinker, initiators and stabilizer) in acetone/water system.
      Morphology of the nanoparticles was examined using scanning electron microscopy
      (SEM). Particle size and zeta potential were measured by dynamic light scattering
      (DLS). Scheffe polynomial models were generated to predict particle size (nm) and
      particle surface zeta potential (mV) as functions of the proportion of the
      components. Solutions were returned from simultaneous optimization of the
      response variables for component combinations to (a) minimize nanoparticle size
      (small nanoparticles are internalized into disease organs easily, avoid
      reticuloendothelial clearance and lung filtration) and (b) maximization of the
      negative zeta potential values, as it is known that, following injection into the
      blood stream, nanoparticles with a positive zeta potential pose a threat of
      causing transient embolism and rapid clearance compared to negatively charged
      particles. In vitro availability isotherms show that the nanoparticles sustained
      the release of docetaxel for 72 to 120 hours depending on the formulation. The
      data show that nanotechnology platforms for controlled delivery of bioactive
      agents can be developed based on the nanoparticles.

PMID- 25980178
TI  - Sustained release matrix tablets prepared from cospray dried mixtures with starch
      hydrophobic esters.
AB  - In this work, starch acetate and propanoate derivatives with moderate degree of
      substitution were synthesized and characterized for employment as matrix formers
      for sustained release from tablets. Matrix tablets were prepared from cospray
      dried and simple physical mixtures of starch/starch derivatives and theophylline
      as a model drug. The release was rapid for matrix tablets prepared from simple
      physical mixtures. On the other hand, tablets prepared from cospray-dried
      mixtures with starch acetate and starch propanoate showed much slower and
      extended release. Scanning electron micrographs of tablet surfaces revealed
      enhanced inter-particulate bonding and plastification for cospray-dried
      agglomerates in comparison with physical mixtures.

PMID- 25980179
TI  - Pharmacological action of DA-9701 on the motility of feline stomach circular
      smooth muscle.
AB  - DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is
      formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to
      determine the pharmacological action of DA-9701 and to identify the receptors
      involved in DA-9701 -induced contractile responsesin the feline gastric corporal,
      fundic and antral circular smooth muscle. Concentration-response curve to DA-9701
      was established. The tissue trips were exposed to methylsergide, ketanserin,
      ondansetron, GR 113808, atropine and dopamine before administration of DA-9701.
      The contractile force was determined before and after administration of drugs by
      a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum,
      corpus and fundus. However, it did not change the spontaneous contractile
      frequency of antrum and corpus, but concentration-dependently reduced that of
      fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by
      dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but
      not by atropine, indicating that the contractile responses are mediated by
      multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus,
      DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but
      not by methysergide, ketanserin or ondansetron, indicating that they are involved
      in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors.
      However, contractile responses to DA-9701 are mainly mediated by dopamine
      receptors in the antrum. These results suggest that DA-9701 has important roles
      in gastric accommodation by enhancing tonic activity of fundus, and in gastric
      emptying and gastrointestinal transit by phasic contractions of corpus and antrum
      mediated by multiple receptors.

PMID- 25980180
TI  - Heat shock protein 90 inhibitor regulates necroptotic cell death via down
      regulation of receptor interacting proteins.
AB  - 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) acts as an inhibitor
      of heat shock protein 90 (HSP 90), which serves as a nodal protein of diverse
      signaling networks leading to a variety of biological implications. HSP90 plays
      the role of a chaperone for a variety of client proteins including receptor
      interacting protein 1 (RIP1). Since RIP1 and RIP3 are, respectively, required for
      zVAD- and tumor necrosis factor alpha (TNFalpha)-mediated necrotic cell death, we
      pursued to address the effects of DMAG on receptor-and nonreceptor-mediated
      necroptotic cell death. DMAG facilitated the degradation of receptor interacting
      protein 3 (RIP3) as well as RIP1, a known client protein of HSP90, in L929 cells.
      Consequently, DMAG rendered cells more sensitive to TNFalpha stimulation while it
      rescued cells from necrotic cell death caused by zVAD. From this study, we
      propose that DMAG-downregulated RIP1 can shift cell death typing from necroptosis
      to apoptosis. In contrast, the protective effect of DMAG on zVAD-induced
      cytotoxicity could be partly explained by the fact that zVAD mediates
      cytotoxicity via a RIP1 -dependent route. In summary, functional disruption of
      HSP90 by DMAG destabilized necroptosis proteins RIP1 and RIP3, which in turn
      regulated zVAD- and TNFalpha-induced necroptosis. Therefore, pharmacological
      modulation of necroptotic cell death through HSP90 could be a promising strategy
      for overcoming cancer drug resistance or protecting ischemic cell death.

PMID- 25980181
TI  - Gracillin induces apoptosis in HL60 human leukemic cell line via oxidative stress
      and cell cycle arrest of G1.
AB  - Gracillin, a kind of steroidal saponin isolated from the root bark of wild yam
      Dioscorea nipponica has been reported to exert antitumor activity. In the present
      study, we investigated the anticancer activity of gracillin against HL60 cells,
      and evaluated the possible mechanism involved in its antineoplastic action. The
      cell proliferation was evaluated by cell counting Kit-8 (CCK-8) assay, gracillin
      inhibited the growth of HL60 cells in a time- and concentration-dependent manner.
      Flow cytometry was used to analyze the cell cycle distribution whereas Annexin V
      FITC/PI flow cytometry analysis was carried out to confirm apoptosis induced by
      gracillin, Our results demonstrated that gracillin could induce cell cycle arrest
      of G1 and apoptosis in HL60 cells. Furthermore, based on the biochemical methods,
      induction of oxidative stress by gracillin was indicated by increased the content
      of malondialdehyde (MDA), and decreased superoxide dismutase (SOD) activity. In
      addition, real time-PCR verified the expression of apoptosis-related genes, the
      mRNA level of Bcl-2 was decreased dramatically, while Bax was remarkably
      increased by gracillin. Taken together, gracillin could induce cell cycle arrest,
      oxidative stress, and apoptosis in HL60 cells, and has the potential to be
      developed as an antitumor agent.

PMID- 25980182
TI  - Antiproliferative and apoptotic potential of Daphne gnidium L. root extract on
      lung cancer and hepatoma cells.
AB  - Daphne gnidium L. (Thymeleacees) is a famous Moroccan plant with cancer-related
      ethnobotanical use. Previously, we demonstrated that ethyl acetate extract of D.
      gnidium had antiproliferative and pro-apoptotic potential on human breast tumor
      MCF-7 cells. The purpose of this study was to investigate if the
      antiproliferative effect of this extract was similar for different human cancer
      cell lines such as A549 lung cancer and SMMC-7721 hepatoma cells. Moreover, this
      work essentially focused on the intrinsic apoptotic signaling pathway.
      Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide on A549 and SMMC-7721 cells. The characterization of
      the mechanisms involved in this effect was determined by lactate dehydrogenase
      test, apoptosis assays and western blot analyses. Our present study has shown
      that this extract strongly inhibited proliferation of A549 (IC50: 213 +/- 15
      MUg/ml) and SMMC-7721 (IC50: 170 +/- 13 MULg/ml) cells. The characterization of
      antiproliferative effect demonstrated that this extract was an apoptosis inducer
      in both cell lines tested. The results of western blot analyses have shown in
      SMMC-7721 cells that this extract activated caspase signaling triggered by the
      modulation of Bcl-2 family proteins. These findings suggest that this natural
      extract-induced effects may have novel therapeutic applications for the treatment
      of different cancer types.

PMID- 25980183
TI  - The privilege against self-incrimination in coroners' inquests.
AB  - The privilege against self-incrimination has a venerable history in the conduct
      of coroners' inquests. However, recent statutory reforms to the privilege in
      coroners' courts, which have had disuniform outcomes throughout Australia, have
      complicated the circumstances in which the privilege is extended to those
      claiming its protection. This editorial reviews the evolving law on the privilege
      generally and rulings that have been made in high-profile coronial inquests, as
      well as the modest volume of appellate litigation on this important issue. It
      identifies that the emerging law on the area prioritises amongst relevant factors
      for the coroner's discretion to exercise coercive powers over witnesses'
      objections to give evidence the fact that they are charged with serious criminal
      offences, and that the need for and utility of the evidence are also functioning
      as important considerations.

PMID- 25980184
TI  - Updating Australia's pandemic preparedness: the revised Australian Health
      Management Plan for Pandemic Influenza (AHMPPI).
AB  - In 2014, Australia updated its health management plan for pandemic influenza.
      This updated plan builds upon the lessons from the 2009 influenza pandemic and
      revised guidance from the World Health Organization. The 2009 pandemic
      highlighted the need for flexibility in responding to pandemics so that responses
      can be tailored according to the severity of a pandemic. Recognition of the need
      for flexibility is a key feature of both the revised WHO guidance and the revised
      Australian plan. This column provides an overview of the updated WHO guidance and
      of the revised Australian Health Management Plan for Pandemic Influenza.

PMID- 25980185
TI  - Cruise control: prevention and management of sexual violence at sea.
AB  - The drug-related death of Dianne Brimble on the P&O cruise liner Pacific Sky in
      2002 triggered a wide-ranging review of the safety on board cruise ships
      operating in the Australian market. This column assesses the frequency of recent
      sexual assaults on cruise ships and examines the findings and recommendations of
      the Brimble inquest, focusing on the Commonwealth government's response to those
      recommendations. The problem of jurisdiction on flag of convenience registered
      ships is discussed, with emphasis on a possible co-operative arrangement between
      Australian police and foreign flag states. It seems likely that the United States
      and Canadian models of cruise ship regulation to enhance passenger safety will in
      part be introduced in Australia.

PMID- 25980186
TI  - Clayton's compromises and the assisted dying debate.
AB  - Richard Huxtable has recently argued that while assisted dying has been both
      repeatedly condemned and commended, a compromise resolution is possible.
      Following critique of other purported solutions, he argues for a new legal
      offence of "compassionate killing" as a plausible compromise between supporters
      and opponents of legalised assisted dying, because it offers something of
      significance to both sides. However, it turns out that "compassionate killing"
      would leave both sides with insufficient net benefit for the proposal to qualify
      as a compromise between them. By analogy with another apparently intractable
      bioethical debate, concerning destructive embryo research, this column rejects
      Huxtable's solution as another "Clayton's compromise". True compromise is not
      possible in bioethical debates involving divisions over deeply held values and
      world views. Resolving such debates inevitably involves the substitution of one
      dominant world view with another.

PMID- 25980187
TI  - Professional misconduct: the case of the Medical Board of Australia v Tausif
      (occupational discipline).
AB  - In 2014, the Australian Capital Territory Civil and Administrative Appeals
      Tribunal (ACAT) made a finding of professional misconduct against a Canberra
      general practitioner working in two bulk-billing medical practices established by
      a corporate medical practice service company, Primary Health Care Limited
      (Medical Board of Australia v Tausif (Occupational Discipline) [2015] ACAT 4).
      This column analyses that case, particularly in relation to the ACAT finding that
      the practitioner's professional misconduct was substantially contributed to by an
      unsafe system of care, specifically, the failure of Primary Health Care to
      provide supervision and mentoring for clinicians working at its medical centres.
      The case highlights the professional pressures carried by general practitioners
      who practise medicine within the framework of corporate bulk-billing business
      models. The column also examines the related issue of general practitioner co
      payments in Australia and their impact on business models built around doctors
      purportedly characterised as independent contractors, bulk-billing large numbers
      of patients each day for short consultations.

PMID- 25980189
TI  - We didn't start this fireless vapour: E-cigarette legislation in Australia".

PMID- 25980188
TI  - "We didn't start this fireless vapour: E-cigarette legislation in Australia".

PMID- 25980190
TI  - Health care justice for temporary migrant workers on 457 visas in Australia: a
      case study of internationally qualified nurses.
AB  - Workers and their families in Australia under the Temporary Work (Skilled) Visa
      (subclass 457) scheme have no access to publicly funded health care. Rather, they
      are required by the Commonwealth government to purchase costly private health
      insurance. Our empirical study revealed the serious negative effects of the
      government's policy on the ability of internationally qualified nurses on 457
      visas to meet their basic health care needs and to settle effectively into
      Australian society This article argues that the current policy is unjust and
      evaluates three options for reform which would accord more fully with the
      government's obligations to minimise harm to people's health and to ensure that
      all people in society have their health care needs met in a fair manner.

PMID- 25980191
TI  - A delayed inheritance: the Medical Board of Victoria's 75-year wait to find
      doctors guilty of "infamous conduct in a professional respect".
AB  - The Medical Board of Victoria (Board) was created in 1844 to register "legally
      qualified medical practitioners". It was not until 1933, however, that the Board
      attained the power to remove from its register a doctor who had engaged in
      "infamous conduct in a professional respect" (the power), even though the General
      Council of Medical Education and Registration of the United Kingdom on which the
      Board was modelled had been granted the power 75 years earlier. This article
      argues that the delay in the Board's inheritance was attributable to successive
      Victorian Parliaments' distrust of the Board and that this attitude was
      unwarranted, at least from early in the 20th century. The article maintains that
      the granting of the power to the Board was a crucial event in the history of the
      regulation of the Victorian medical profession. This is illustrated both by the
      difficulty encountered by the medical profession in dealing with doctors'
      unethical conduct before 1933, and the Board's concern to use its new authority
      responsibly and appropriately to protect the public and the profession in the
      three years after it attained the power.

PMID- 25980192
TI  - Correcting the record: Australian prosecutions for manslaughter in the medical
      context.
AB  - The failure to prosecute Dr Jayant Patel successfully for any of the deaths
      associated with his time as Director of Surgery at Bundaberg Base Hospital was
      received in some quarters as an abject failure of the criminal law to deal
      adequately with significant wrongdoing. The case itself, the multiple public
      inquiries and the significant expense to pursue, extradite and prosecute Patel,
      resulting finally in a finding of guilt on a number of minor fraud charges, seems
      to compound this sense of failure. This article argues otherwise. When placed
      within the far longer and forgotten history of the prosecution of manslaughter by
      criminal negligence in the Australian jurisdiction, this story of prosecutorial
      failure becomes instead wholly consistent with the case law over time. No
      adequate account of the history of prosecution in the Australian jurisdiction
      exists for this area of law. To present Patel in context, the article draws upon
      archival research to provide a significantly extended account of the history of
      prosecution for manslaughter in the health care context. The extension of the
      case law is significant, from four known prosecutions, case histories of another
      33 inadequately acknowledged prosecutions are presented.

PMID- 25980193
TI  - Adapting to concurrent expert evidence in medical litigation.
AB  - In medical negligence litigation expert evidence has long played a dominant role.
      The trend towards the use of concurrent expert evidence is now well underway.
      However, for the lawyers and the doctors involved, the pathway is not yet
      familiar. Disputes have frequently arisen in the context of pre-hearing expert
      conclaves, given the adversarial nature of litigation and perhaps fuelled by
      fears of a less transparent process at this increasingly important stage. This
      article explains the concurrent expert evidence framework and examines areas of
      common dispute both in the conclaves and at trial, with a view to providing
      assistance to legal practitioners working in this area and the medical
      practitioners called upon to provide expert evidence in such litigation.

PMID- 25980194
TI  - "Loss of situation awareness" by medical staff: reflecting on the moral and legal
      status of a psychological concept.
AB  - This article examines the emergence of "accurate situation awareness (SA)" as a
      legal and moral standard for judging professional negligence in medicine. It
      argues that SA constitutes a status, an outcome resulting from the confluence of
      a wide array of factors, some originating inside and others outside the agent. SA
      does not connote an action, a practice, a role, a task, a virtue, or a
      disposition--the familiar objects of moral and legal appraisal. The argument
      contends that invoking SA becomes problematic when its use broadens to include
      professional or legally appraisable norms for behaviour, which expect a certain
      state of awareness from practitioners.

PMID- 25980195
TI  - Coroners' guidelines for health practitioners: help or hindrance?
AB  - In Victoria, New South Wales and Queensland, coroners' guidelines have been
      developed to assist health practitioners in complying with their coronial
      reporting obligations. These guidelines, which are intended to work hand in hand
      with the legislation, leading the health practitioner through the law, its
      interpretation and its application, have been commended for assisting with a more
      detailed and structured consideration of often complex issues. However, closer
      scrutiny of these guidelines shows legal inaccuracies and other errors that have
      the potential to lead health practitioners into error. In circumstances where
      failure to comply with reporting obligations can constitute a criminal offence as
      well as professional misconduct, this situation is unacceptable. This article
      recommends changes to the guidelines to bring them into conformity with the law
      ensuring that the guidelines operate as a help, and not a hindrance, to health
      care practitioners.

PMID- 25980196
TI  - Unfair employment discrimination of previously depressed individuals.
AB  - Individuals who have recovered from or are in a remissive state of depression are
      often required to declare their psychiatric history during applications for
      employment. This practice exposes such individuals to discrimination even though
      they are no longer afflicted by the condition, leading to the question whether
      the practice is fair and justified. Such discrimination can also have adverse
      health implications as individuals with active depression might not want to seek
      help early for fear of stigmatisation. In this article, constructive dialogue
      among relevant stakeholders is proposed to encourage appropriate and measured
      responses to this problem. A more durable solution in Singapore may be to
      introduce legislation to prevent unfair discrimination.

PMID- 25980197
TI  - The decision-making of the Mental Health Review Tribunal in New Zealand.
AB  - This article reports the findings of a qualitative research project that explored
      the decision-making of the Mental Health Review Tribunal in New Zealand,
      providing "thick descriptions" of the hearing process by closely focusing not
      only on the content of final written decisions, but also how decisions are made
      and delivered within the context they are formed. Drawing on interviews with
      tribunal members (n = 14), observation of hearings (n = 11), and review of
      written decisions (n = 60), the article illustrates how the MHRT attempts to
      practise in a way that enhances rather than damages ongoing relationships between
      applicants and clinicians. The factors that constrain its ability to conduct a
      hearing perceived as fair and participatory by the applicants is considered, and
      synergies with the international literature are noted in relation to the heavy
      use of medico-legal language, dominance of public safety concerns, and the covert
      interventionist practices of the MHRT. The article concludes by highlighting the
      value of qualitative observations of this decision-making body. While written
      decisions provide a justification for the outcome decided by the MHRT it leaves
      out nuances gleaned from in-depth clinical reporting, inquisitorial investigation
      and unwritten observations during hearings.

PMID- 25980198
TI  - Re-visiting Re X: hysterectomy, removal of reproductive capacity and the severely
      intellectually disabled child in New Zealand.
AB  - The law governing parental consent to any surgery performed on an intellectu-
      ally disabled minor that results, directly or indirectly, in the loss of
      reproductive capacity was first considered in New Zealand in the High Court case
      of Re X in 1991. The decision was remarkable in several respects, not least
      because it reflected a genuine attempt to obtain a representation of interests
      beyond those of the particular child and parents involved. However, legal and
      socio-political developments in the intervening years, both locally and
      internationally, suggest that a review of the decision is timely. This article
      questions whether, in light of these events, Re X should be revisited and
      concludes by suggesting a possible legal response.

PMID- 25980199
TI  - An alternative to Zoe's Law.
AB  - Under the criminal law of New South Wales, the destruction of a foetus (other
      than in the course of a medical procedure) constitutes grievous bodily harm to
      the pregnant woman. Charges can be laid for offences against the woman, but not
      against the foetus. Many are dissatisfied with this. The Crimes Amendment (Zoe's
      Law) Bill 2013 (No 2) (NSW) aimed to change this by providing that a foetus is
      taken to be a living person for the purposes of certain offences. The Bill was
      strongly opposed on the basis that according personhood to a foetus in this way
      will have undesirable consequences that could erode the reproductive rights of
      women. The public debate over how the criminal law addresses the destruction of a
      foetus has centred on Zoe's Law. This article proposes an alternative amendment.
      that aims, to accommodate the concerns of the Bill's supporters and its
      detractors.

PMID- 25980200
TI  - Consistent high performers. Truven 100 Top Hospitals focus on standardization to
      improve outcomes and reduce costs.

PMID- 25980201
TI  - Downsizing innovations. Devicemakers developing new surgical options for obesity.

PMID- 25980202
TI  - The economic and political consequences of King v. Burwell.

PMID- 25980203
TI  - Keep 340B savings where they belong--with patients and communities.

PMID- 25980204
TI  - Hospital reduces delirium in patients.

PMID- 25980206
TI  - Biggest 2014 price changes on purchased items. Selected high-spend hospital
      products and devices, ranked by percentage change.

PMID- 25980205
TI  - How do we replace jobs lost when we downsize hospitals?

PMID- 25980207
TI  - Changing your mind. A new initiative wants to make mental health a priority.

PMID- 25980208
TI  - [An automated information system for monitoring the health of schoolchildren].

PMID- 25980209
TI  - [A mobile system for automated remote monitoring of cardiac activity].

PMID- 25980210
TI  - [Application of the method of gas chromatography-mass spectrometry for assessing
      the state of intestinal microflora].

PMID- 25980211
TI  - [Thermometric control of phototherapy].

PMID- 25980212
TI  - [Determination of parameters of capillary blood flow using video data analysis].

PMID- 25980213
TI  - [Mathematical modeling of hemodynamic characteristics of blood pumps for
      pulsative ventricle assist systems].

PMID- 25980214
TI  - [Effect of pulsatile flow and back washing on the plasma flow rate in
      plasmapheresis. Part 1. Theory].

PMID- 25980215
TI  - [Mathematical modeling of test electrocardiosignals].

PMID- 25980216
TI  - [Development and testing of the virtual encephalograph].

PMID- 25980217
TI  - [The software for jam-resistant sampling of analog EEG records on paper].

PMID- 25980218
TI  - [Use of fuzzy logic decision making in medical expert systems].

PMID- 25980219
TI  - [Biomedical sensors of deformation and humidity based on carbon nanotubes].

PMID- 25980220
TI  - [Specific features of cryodestruction of the prostate].

PMID- 25980221
TI  - [Possibilities of use of the "Amplipuls" device in treatment of the partial
      atrophy of the optic nerve of traumatic genesis].

PMID- 25980222
TI  - [Systemic inflammation: theoretical and methodological approaches to description
      of general pathological process model. Part IV. A dynamics of the process].
AB  - Systemic inflammation (SI) as a general pathological process is considered as a
      development of cellular stress in response to systemic action of damage factors.
      An Acute SI is characterized by wavelike course (a changing of activation and
      inhibition phases); a chronic SI is characterized by successive changing of
      stages of its progressive development. SI may be classified into three variants
      which are dependened on intensity of systemic alteration as well as on condition
      of anti-inflammatory systems: 1) a "break" is a fulminating process (e.g.
      fulminating sepsis), 2) a "caving" is a relatively gradual conversion of
      classical inflammation to systemic one; 3) a "sticking" is a typical chronic SI.
      An evolution of the acute SI is characterized by the 5 following phases: a
      development, hyperergic phases of the primary and the secondary phlogogenic
      impact, a resolution, and depressive phase. The last phase is a typical for the
      "break" variant and characterized by a tolerance, but not a resistance strategy
      to action of factors of systemic alteration. It is advisable to estimate SI with
      Integral Criteria (Scales), which reflect both of the development of a systemic
      inflammatory response and the following other particular processes of SI: the
      systemic alteration, the micro thrombosis and other microcirculatory disorders,
      multiple organ dysfunction, and a distress of the neuroendocrine system.

PMID- 25980223
TI  - [Agonists of 5HT2C-receptors SCH 23390 and MK 212 incresase the force of rat
      aorta contraction in the presence of vasopressin and angiotensin II].
AB  - We investigated the role of 5HT2C receptors in regulation of blood vessel
      contractility. We determined expression of 5HT2C receptors in smooth muscle cell
      line A7r5 as well as on isolated rat aorta. It was shown that strong
      vasoconstriction effect of 5HT2C receptor agonists - SCH 23390 and MK 212
      appeared on blood vessels after preliminary activation of angiotensin ATIA- and
      vasopressin V1A-receptors. Biphasic contraction (a rhythmic alternation of
      contraction and subsequent relaxation phases of aoitic rings) and tonic
      contraction were observed in 75% and 25% of the cases after 5HT2C receptor
      activation, respectively. Periodic high amplitude constrictions of isolated rat
      aorta, induced by SCH 23390 and MK 212 agonists, were persisted for a long time
      (>1 hour). It was revealed that calmodulin and c-Src kinase play a central role
      in the mechanisms of signal transduction from 5HT2C receptors. Trifluoperazine
      and PP2, the inhibitors of calmodulin and c-Src kinase, respectively, abolished
      vasoconstriction reaction of isolated aortic rings in response to SCH 23390 and
      MK 212 but did not affect the strength gain of the vasoconstriction caused by
      fluoroaluminate, a G-protein activator. Taken together, these date suggest that
      5HT2C receptors are in a latent state in blood vessels (<<silent>> receptors) and
      activation of these receptors is dependent on the functional state of the
      receptors of other endogenous vasoconstrictors.

PMID- 25980224
TI  - [Effect of course intake of bio-active flavonoids-containing plant preparation
      Extralife on the level of anxiety and sensorimotor reactivity in rats].
AB  - Clinical and epidemiological data evidence the need to search for new substances
      for treatment and prevention of increased anxiety associated with emotional and
      neurotic breakdown and worsening clinical prognosis of psychosomatic diseases. Of
      particular interest are the drugs of plant origin, which are generally well
      tolerated under prolonged use, and treat- ment is cheaper as compared with modem
      anxiolytics. The purpose of this study was to investigate the effects of course
      taking a flavonoid-containing plant preparation Extralife (water-soluble extract
      Pentaphylloides fruticosa, 40 mg/kg per day for 1 month) in <<anxious>> and <<non
      anxious>> inbred albino rats sampled in the population using a multi-parameter
      method for evaluating anxiety-phobic states. This method was also used for
      evaluating the severity of anxiety (state anxiety) in rats in the dynamics of the
      survey. Sensorimotor reactivity (emotionality) was assessed by the parameters of
      the acoustic startle response. Extralife did not prevent the increase in state
      anxiety in <<non-anxious>> rats and did not change the level of anxiety in the
      <<anxious>> animals. However, the drug reduced the amplitude of the acoustic
      startle response in the <<anxious>> animals and increased startle response
      latency in both <<anxious>> and <<non-anxious>> rats, that is reduced the
      symptoms of anxiety caused by alarm sound stimuli in terms of sensorimotor
      reactivity. The data testify to the anxiolytic and sedative effects of Extralife
      more pronounced in the <<anxious>> animals. In a course intake of Extralife <<non
      anxious>> rats demonstrated transient decrease in the pre-pulse inhibition of the
      acoustic startle response, probably associated with the occurrence of transient
      disturbances in the psycho-emotional sphere. The findings suggest that Extralife
      in a course taking may have negative side effects on the emotionality of <non
      anxious> animals that determines the need to incorporate the features of mental
      and emotional status of the individual in the development of therapeutic
      approaches to the correction of high anxiety with the inclusion of the drug.

PMID- 25980225
TI  - [Role of the glutathione system in regulation of redox status in the rat cerebral
      cortex under hypoxia].
AB  - The study compared effects of different hypobaric hypoxia regimens (14% O2, 10.5%
      O2, and 8% O2; 1 hour; 15 days) on parameters of the glutathione system,
      intensity of free radical oxidation, and intensity of lipid peroxidation in
      cerebral cortex (CC) of rats with different, genetically predetermined resistance
      to acute hypoxia. In normoxia, baseline concentrations of oxidized glutathione
      (0.155 +/- 0.011 nmol/mg protein) and hydroperoxide metabolites (50.4 +/- 2.62
      cumene hydroperoxide equivalents/g tissue) were 20% lower in CC of low-resistance
      (LR) rats than in high-resistance (HR) rats (0.191 +/- 0.013 nmol/mg protein;
      63.0 +/- 3.46 cumene hydroperoxide equivalents/g tissue, respectively). Baseline
      activities of the glutathione cycle enzymes, glutathione peroxidase (31.2 +/-
      1.59 nmol/min/mg protein) and glutathione reductase (28.5 +/- 1.49 nmol/min/mg
      protein), were 30% lower in LR rat CC than in HR rat CC (47.0 +/- 2.41; 433 +/-
      2.26 nmol/min/mg protein, respectively). These data suggested more efficient
      antioxidant defense of CC tissue in LR rats than in HR rats. The phenotypic
      difference in CC tissue redox properties between two rat phenotypes remained in
      hypoxia. The efficiency of glutathione system in regulation of CC redox
      homeostasis was shown to depend on both severity and duration of hypoxic
      exposures and on individual tolerability of hypoxia, i.e., this efficiency was
      genetically predetermined. The glutathione system maintains its regulatory
      properties in a broader range of lowered pO2 values and during longer hypoxic
      exposures. in LR rat CC than in HR rat CC. For this reason, activation of free
      radical processes and development of oxidative stress induced by single or
      repeated hypoxic exposures are prevented or alleviated in LR rat CC but not in HR
      rat CC. The obtained data strongly justify the need for selection of hypoxic
      exposure regimens for therapeutic hypoxic preconditioning. Apparently the hypoxic
      exposures not associated with signs of oxidative stress should be considered
      optimum.

PMID- 25980226
TI  - [The role of adenosine Al receptors and mitochondrial K+ATP channels in the
      mechanism of increasing the resistance to acute hypoxia in the combined effects
      of hypoxia and hypercapnia].
AB  - We studied the role of the role of mitoK+ATp channels and Al-adenosine receptor
      in the mechanism of increasing the resistance to acute hypoxia after hypoxic,
      hypercapnic and hypercapnic-hypoxic preconditioning. It is shown that
      mitochondrial ATP-sensitive potassium channels and Al-adenosine receptors, an
      important mechanism of preconditioning have a high value to increase the
      resistance to acute hypoxia/ischemia in the combined effect of hypoxia and
      hypercapnia. However, with regard to the adenosine receptor, this mechanism is
      realized without the participation hypercapnic component, which apparently starts
      neuroprotection without activation of the adenosine Al receptors.

PMID- 25980227
TI  - [Pathological changes after brain ischemia are similar to those observed in
      Alzheimer disease].
AB  - We studied the influence of ischemia/reperfusion of the middle cerebral artery in
      the rat's brain on the deferred violation of cognitive functions of the brain
      which are similar to main symptoms observed in the development of Alzheimer's
      disease. Using 8-hose radial labyrinth we demonstrated that 6 months after
      incidence of cerebral ischemia a significant impairment of working memory and a
      decrease in animals the ability to learn are developed. 7 months after focal
      cerebral ischemia we could observe the accumulation of a mature amyloid peptide
      and hyperphosphorylated form of the Tau pro- tein in ipsilateral cerebral
      hemisphere and of the the beta-amyloid peptide precursor in the contralateral
      hemisphere. Thus, after an experimental stroke in the brain pathological chanres
      occur as those typical of Alzheimer's disease.

PMID- 25980228
TI  - [Peculiarity of autonomic functions regulation remodeling in human adaptation to
      extreme conditions in labor activities].
AB  - In modem society, professional activity in conditions of extreme factors occupies
      a growing place. Of particular note is the work related to night shifts involving
      up to 20% of the population. In some cases, this work may lead to a breach of the
      adaptation processes of the body and increase the risk of diseases. The necessity
      to search criteria of dysregulation changes in the human body during adaptation
      to extreme conditions in labor activities is the actual problem from the
      standpoint of preventive health care of the working population health and
      providing safety in professional activities conditions. In our work, we attempted
      to identify early signs of autonomic function's dysregulation by analyzing the
      heart rhythm variability in locomotive operators and doctors on duty. It was
      revealed that these groups of people with different levels of intensity of
      professional activities may be the model for observation of the stages of
      dysregulation process. It is also shown that the earliest markers of autonomic
      regulation remodeling are indicators of the spectral analysis of heart rhythm
      variability, reflecting the activity of the total power regulation (TP) and
      parasympathetic part (HF).

PMID- 25980229
TI  - [The changes in the biochemical indices of blood in cobalt intoxication on the
      background of the regulators of the expression of endothelial NO-synthase].
AB  - On the background of chronic cobalt intoxication in rats develops oxidative
      stress. This is accompanied by a decrease in the content of total metabolites of
      nitric oxide in the blood serum. The reasons for lower levels of the
      vasodilatation factor are the following: a deficiency of L-arginine and the
      increase in the content of the inhibitor of NOS-3. We found a decrease in the
      bioavailability of nitric oxide due to the increase in the content of oxidized
      low density lipids, total cholesterol and cholesterol-lowering lipids high
      density.

PMID- 25980230
TI  - [Neurotoxic the effects of chemotherapy on the function of the central nervous
      system in children with lymphoid tumors].
AB  - INTRODUCTION: In children with lymphoid tumors (LT) chemotherapy is the main
      treatment. It is known, that many chemotherapy drugs have toxic effects on the
      central nervous system and is a factor, that leads to significant cognitive
      impairment. Purpose: Search of neurophysiological, neurochemical, and
      psychological correlates of neurotoxicity in children with LT when programmed
      therapy. MATERIAL AND METHODS: The study included 39 children (4-16 years) with
      LT, with acute lymphoblastic leukemia (ALL) - 25, with non-Hodgkin's lymphoma
      (NHL) - 14 who were treated according to the scheme m-BFM-90: for patients with
      ALL (mALL-BFM -90) and the NHL (mNHL - BFM-90). Investigated the EEG, REG, ECHO
      EG. In 12 children with LT in blood serum levels of middle molecules (MM) -
      indicator of general toxicity, N-acetylneuraminic acid (N-ANA) - indicator of
      neurotoxicity, malondialdehyde (MDA) - lipid peroxidation, tocopherol, retinol -
      indicators of antioxidant protection, level of catalase - as free radical oxida-
      lion; vanilmindalic acid levels (VMA) - as indicator of the state
      catecholaminergic system. Studies were performed before treatment, after
      induction of remission, after M-protocol, after the end of chemotherapy. In 23
      children (11-16 years) with LT during chemotherapy, performed a comparison of EEG
      and the level of anxiety (Ch.D.Spilberger), <<strategy selection behavior>>
      (Thomas-Kilman). Control group - healthy children of the same age. RESULTS: The
      main results obtained in the present study were that 1) Prior to initiation of
      treatment of children with LT had a EEG changes, indicating certain dysfunction
      of diencephalic structures of the brain, and probably due to metabolic disorders
      that affect the neurotransmitter metabolism. 2) Toxic effects of chemotherapy on
      the CNS program was shown on a range of indicators: according to EEC-increasing
      values of relative power in the band delta- and Theta-frequency range, lower
      alpha-activity, increase of relative power in the band betal,2; according to REG
      hemodynamic compromise; increasing levels of neurochemical indicators N-ANA and
      the VMA. This was accompanied by behavior strategies <<adaptation>> and
      <<cooperation>>, are not peculiar to healthy peers. Identified individual
      predictors of neurotoxicity in the software of chemotherapy in children with LT.

PMID- 25980231
TI  - [Possible mechanism of the selective action of the inhibitors of glycolysis in
      the endothelial cells and the human carcinoma cells in the culture].
AB  - It is known that the production of energy and synthesis of macromolecules in
      cancer cells depend on the glucose metabolism to a greater extent than in non
      tumor. In this paper we carry out a comparative study of the effectiveness of the
      two modifiers glycolysis 2 - D-deoxyglucose (2-DG) and dichloroacetate (DCA) in
      the induction of the cell death, changes in the cell cycle progression and in the
      alteration of the intracellular ROS levels in endothelial cells (line ECV304) and
      human carcinoma cells (line HeLa G-63) in order to identify cause-effect
      relations between these events. It has been shown that inhibition of the various
      stages of the glycolysis result in blocking cells in C2/M phase of the cell cycle
      and the induction of the cell death. This effect was record for HeLa G-63 cells
      only. DCA is inhibitor of the pyruvate dehydrogenase kinase and 2-DG is inhibitor
      of the glucose transport and glycosylation induced selective dose-dependent
      cytotoxic effect in HeLa G-63 cells. The increase of intracellular levels of the
      oxygen radicals induced by DCA in the cells HeLa G-63 suggests that the cytotoxic
      effect of the DCA is mediated by activation of the mitochondrial functions. The
      cytotoxic effect of 2-DG depend on the level of glucose in the culture medium,
      therefore we suggest that not only the oxidative stress, but and the energy
      depletion involved in selective response of the cancer cells on the actions of
      the inhibitors of glycolysis.

PMID- 25980232
TI  - [Cytokines profile and metabolic activity of neutrophils of peripheral blood when
      progressing neoplasma].
AB  - The neutrophil is considered as the peculiar monocelled sekretorny gland
      realizing the effector potential including by secretion of soluble products -
      cytokines and for today. Influence of a tumor on functional activity of
      neutrophils depends on type, localization and a stage of its development. In our
      research dynamics of metabolic and of neutrophils of peripheral blood, the
      contents in a lysate and serums of blood of cytokines of IL-1beta, 1Ra, 2, 6, 10,
      18, TNF-alpha, IFN-gamma and is studied when progressing a cervical cancer.
      Cytokines and metabolism indicators - activity of, determined by an
      immunofermental method, level of cationic proteins, a share of active cages in
      the spontaneous NST-test were cytochemical. It is shown that when progressing
      cervical cancer against increase in total of neutrophils significant decrease in
      their, aerobic and anaerobic bacterial action, decrease in the IL-1beta and IL-1
      Ra level, and also IFN-gamma takes place at TNF-alpha increase, increase of
      production of matrix metalloproteinas-2 on Ib-IIa of a stage of a disease that
      allows to assume emergence at this stage of cervical cancer of pro-tumoral effect
      of neutrophils.

PMID- 25980233
TI  - [Influence of the nitric oxide donors on the microcirculation in infusion therapy
      of the experimental hemorrhagic shock].
AB  - Infusion of the nitric oxide donors L-Arginine (150 mg/kg bolus) and Oxacom (3,2
      uM/ kg bolus) with saline solution has been shown improves cardiovascular and
      metabolic changes in animal model of hemorrhagic shock. As a result improves
      survival rats. These data made this effect clinically attractive.

PMID- 25980234
TI  - [The importance of the cortex and subcortical structures of the brain in the
      perception of acute and chronic pain].
AB  - This review presents the current data in the literature about the importance of
      the cortex and subcortical structures of the brain in the perception of acute and
      chronic pain. Discussed the importance of various areas of the brain in
      perception discriminative and affective components of pain. Discusses also gender
      differences in pain perception depending on the functional activity of brain
      cortex and antinociceptive subcortical structures. Analyzed the morphological
      changes of cortical and subcortical structures of the brain in chronic pain
      syndromes. It is proved that the decrease in the volume of gray and white matter
      of cerebral cortex and subcortical structures is a consequence and not the cause
      of chronic pain syndrome. Discusses the features activate and deactivate certain
      areas of the cortex of the brain in acute and chronic pain. Analyzed same
      features the activation of several brain structures in migraine and cluster
      headache.

PMID- 25980235
TI  - [Molecular mechanisms of modulation of lipolysis in adipose tissue and
      development of insulinresistance in diabetes].
AB  - Analysis of modern literature data as well as the results of personal research on
      development of oxidative stress in adipose tissue in diabetes is presented.
      Mechanisms of modulation of spontaneous and induced lipolysis in adipocytes in
      conditions of oxidative stress are discussed. Participation of adipose tissue in
      forming insulin resistance in types 1 and 2 diabetes is considered.

PMID- 25980236
TI  - [Experience of culturing anterior epithelial corneal cells from human eye ball].
AB  - Adult corneal epithelium is often exposed to environmental stress, injured and
      repaired by limbal stem cells. Injury of corneal epithelial layer leads to
      reduction of visual clarity and loss of vision. Recently it was shown that
      epithelial layer also contains stem cells. Obtaining cell culture of corneal
      epithelium will allow understanding mechanisms of cell behavior and
      differentiation, their metabolism and reaction on environmental stress in health
      and disease. Moreover, cultured corneal epithelial cells can be considered as a
      promising material for constructing bioartificial cornea. The aim of this study
      was to isolate cells of anterior corneal epithelium from human donor cornea and
      to study their morphological and functional characteristics in vitro. The results
      of our study showed the possibility of culturing epithelial cells in vitro. The
      observed changes in cell morphology, their flow growth character as well as
      active proliferation and up-regulation of mesenchymal markers expression,
      indicate, in our opinion, epithelial-mesenchymal transition taking place in long
      lasting culture of human anterior corneal epithelial cells. The obtained cultures
      can be used for further studies of pathological processes taking place in cells
      during drugs testing or controlling the phototoxic effect of different types of
      emission.

PMID- 25980237
TI  - [Possibility of diagnostics of the non-steroidal anti-inflammatory drugs
      intolerance with a change in the chemiluminescent glow of the polymorphonuclear
      leukocytes of the peripheral blood].
AB  - We investigated the intensity of barium sulfate stimulated luminol-dependent
      chemiluminescence (SLCL) of pre-incubated blood with various concentrations of
      sodium salicylate, sodium metamizol or sodium diclofenac. Blood was received from
      healthy donors and patients with intolerance to aspirin and/or sodium metamizol
      and/or sodium diclofenac. Revealed valid differences in SLCL of blood received
      from healthy donors and patients with intolerance to these drugs allows us to use
      chemiluminescence method for the diagnosis of intolerance to non-steroidal anti
      inflammatory drugs.

PMID- 25980238
TI  - [Estimation of atherogenic immune complexes containing modified lipoproteins in
      complement fixation tests].
AB  - A method for determining atherogenicity of the immune complexes containing
      multiple modified low-density lipoprotein (mmLDL) in complement fixation test has
      been found. In the proposed method, the precipitate immune complexes containing
      mmLDL (IC mmLDL) was prepared from human serum by treating it with buffer (8.3%
      of th PEG 3350 and 3.3% PVP 12600 th in the ratio 1: 1.2) for 10 min at 23 
      degrees C. IC mmLDL aggregates were separated by centrifugation at 3100g for 10
      min at 23  degrees C. The precipitate IC mmLDL was dissolved in buffer without
      PEG and PVP, cholesterol content and the degree of binding of guinea pig
      complement were measured. Atherogenicity of the IC mmLDL was registered as the
      ratio of the degree of complement binding to cholesterol in the the immune
      complexes.

PMID- 25980239
TI  - [The physician-philosopher - Donat Semenovich Sarkisov. To the 90 anniversary
      since birth].
AB  - The huge and promptly increasing volume of the actual material of modern biology
      and medicine without its systematization doesn't develop any more, and slows down
      development of science. The science as the work which are explaining world around
      needs to bring a system in chaos of the facts. This can be done only on the basis
      of the philosophy of dialectical materialism, which allows an objective,
      realistic to create theoretical generalizations of the ocean of particulars.
      Donat Semenovich Sarkisov who agreed the main phenomena of the general pathology
      with modem biological sciences, modern clinical practice, materialistic
      dialectics was the genial philosopher.

PMID- 25980240
TI  - The world's Ebola response.

PMID- 25980241
TI  - Rules of the road.

PMID- 25980243
TI  - Powered air purifying respirators: versatility beyond respiratory protection.

PMID- 25980242
TI  - Confined space: managing exposures.

PMID- 25980244
TI  - Fit testing industry professionals can trust.

PMID- 25980245
TI  - Employee protection: the hierarchy of controls.

PMID- 25980246
TI  - Gloves are PPE and more.

PMID- 25980247
TI  - Get the cut resistance your workers require.

PMID- 25980248
TI  - No easy answers on vibration gloves.

PMID- 25980249
TI  - Laying the groundwork.

PMID- 25980250
TI  - Fall protection vs. fall prevention: a new approach to ladders.

PMID- 25980251
TI  - What you need to know about fall protection training.

PMID- 25980252
TI  - Identifying same-level slip and fall hazards in the workplace.

PMID- 25980253
TI  - Staying on your feet in the winter.

PMID- 25980254
TI  - Revving up V2V.

PMID- 25980255
TI  - Business and safety: are the strategies aligned?

PMID- 25980257
TI  - IAFC's near miss reporting system begins a new chapter.

PMID- 25980256
TI  - Fresh ground leadership.

PMID- 25980258
TI  - Let's see how we can grow our safety.

PMID- 25980259
TI  - Taking the lead on chemical substitution.

PMID- 25980260
TI  - Keys to optimal flue gas analysis.

PMID- 25980261
TI  - Transitioning from old traditions to a BBS process.

PMID- 25980262
TI  - A state of constant readiness.

PMID- 25980263
TI  - Taming the arc.

PMID- 25980264
TI  - FR compliance vs. protection: an important distinction.

PMID- 25980265
TI  - Winter hazards in manufacturing.

PMID- 25980266
TI  - Raising awareness in your organization.

PMID- 25980267
TI  - Strategic benefits of personal emergency ID.

PMID- 25980268
TI  - Client and contractor: aligning safety cultures.

PMID- 25980269
TI  - Exempting or exemplifying leadership?

PMID- 25980270
TI  - App-based studies bring promise, peril.

PMID- 25980271
TI  - Faulkner to place her own stock in foundation to keep Epic private.

PMID- 25980272
TI  - Daughters upbeat after Prime exits deal.

PMID- 25980273
TI  - Will new Medicare ACO model enable providers to truly manage care?

PMID- 25980274
TI  - Rebuilding a quality culture at HCA.

PMID- 25980275
TI  - Leading in cancer prevention and care.

PMID- 25980276
TI  - Hurt by ACA exchanges, eHealth cuts 160 jobs.

PMID- 25980277
TI  - Mothers' helpers. Providers, insurers use home visits to reduce infant mortality.

PMID- 25980278
TI  - The spending slowdown is real.

PMID- 25980279
TI  - Professional organizations like the ACHE help leaders adapt to evolving industry.

PMID- 25980280
TI  - Retail stores become outpatient centers.

PMID- 25980281
TI  - Private ownership is better if you want to do a good job for your customers.

PMID- 25980282
TI  - Largest master's programs in health administration. Ranked by total full-time
      enrollment in 2014-15 academic year.

PMID- 25980284
TI  - [Lipids in nuclei of neocortex neurons and glia under CNS-syndrome in rats].
AB  - The effect of a local exposure of rat heads to X-ray radiation at a dose of 200
      Gy on the number of phospho- lipids and neutral lipids in the nuclear fraction
      ofneocortex neurons and glia has been investigated A decrease in the amount
      ofphosphatidylinositol and an increase in sphingomyelin in neuronal nuclei
      occurred 2 h after irradiation at the time of repair of locomotive disorders. The
      amount of phosphatidylcholine and phosphati- dylinositol dropped, and the amount
      of sphingomyelin and cholesterol increased in the nuclei ofglial cells of the
      neocortex. Sphingomyelin, phosphatidylinositol, phosphatidylcholine and
      cholesterol of neuronal nuclei are involved in the dynamics of the CNS syndrome
      in mammals. Radio resistance of the responses of lipid nuclei in mammals with the
      CNS syndrome has been shown and a possible role of lipids in the post-irradia-
      tion DNA repair has been suggested.

PMID- 25980283
TI  - [Radiobiological Human Tissue repository: progress and perspectives for solving
      the problems of radiation safety and health protection of personnel and
      population].
AB  - Radiobiological Human Tissue repository was established in order to obtain and
      store biological material from Mayak PA workers occupationally exposed to
      ionizing (alpha- and/or gamma-) radiation in a wide dose range, from the
      residents exposed to long term radiation due to radiation accidents and transfer
      of the samples to scientists for the purpose of studying the effects of radiation
      for people and their offspring. The accumulated biomaterial is the informational
      and research potential that form the basis for the work of the scientists in
      different spheres of biology and medicine. The repository comprises 5 sections:
      tumor and non-tumor tissues obtained in the course of autopsies, biopsies,
      surgeries, samples of blood and its components, of DNA, induced sputum, saliva,
      and other from people exposed or unexposed (control) to radiation. The
      biomaterial is stored in formalin, in paraffin blocks, slides, as well as in the
      freezers under low temperatures. All the information on the samples and the
      registrants (medical, dosimetry, demographic, and occupational data) was obtained
      and entered into the electronic database. A constantly updated website of the
      repository was developed in order to provide a possibility to get acquainted with
      the material and proceed with application for biosamples for scientists from
      Russia and abroad. Some data obtained in the course of scientific research works
      on the basis of the biomaterial from the Repository are briefly introduced in the
      review.

PMID- 25980285
TI  - [Regularities of the highest synergistic interaction display].
AB  - The synergistic interaction effects of various physical and chemical
      environmental factors on cells of different origin are presented. Some general
      patterns of biological manifestations of synergy are analyzed. It is shown that
      synergistic interactions may be revealed only within a certain range of acting
      agents and within this range there is an optimum value at which the greatest
      effect is observed. Possible mechanisms of these effects and their practical
      usefulness are discussed.

PMID- 25980286
TI  - [Modification of radiosensitivity in maignant and normal tissues during
      radiotherapy of malignant neoplasms].
AB  - The results of treatment of cancer patients have not undergone any significant
      changes in recent years. This is due to the fact that opportunities to improve
      the outcomes by developing radiation therapy equipment and op- timizing the dose
      delivery are largely exhausted. However, there is a proven, but practically not
      utilized way--the use of radiomodifiers. This paper presents the experience of
      more than 25 years of clinical use of radiomodification in the Russian Scientific
      Center of Radiology and Modern Surgery Technologies. Simplicity, avai- lability,
      and stability of the results allow considering the use of radiomodification as
      one of the possible ways to improve the effectiveness of radiotherapy.

PMID- 25980287
TI  - [The epididymal adipose tissue of mice after nanosecond pulse-periodic microwave
      irradiation].
AB  - The effect of pulse-periodic microwave radiation (PPMR) of the pulse repetition
      frequency of 8-25 pulseper second, the peak power density of 1500 W/cm2 on the
      epididymal adipose tissue of micewas investigated. The effect was assessed by the
      changes in the fat mass and size of the irradiated adipocytes. It was found that
      the fat mass and size distribution of adipocytes are affected by irradiation. The
      effects depend on the pulse repetition frequency and intensity of exposure.

PMID- 25980288
TI  - [Application of deactivating properties of some sorbents in aquaculture feed
      production].
AB  - The possibility and effectiveness of application of selective sorbents for fish
      feed production in aquaculture in the area exposed to the radioactive pollution
      were studied. The investigations of the fish feed deactivating properties with
      additives of ferrocyn and potassium alginate, and magnesium on whitefish fry
      fingerlings and yearlings were carried out. The study has shown that the ferrocyn
      performance is greater than 99% regardless of the fish age. 1% ferrocyn addition
      to feed allows increasing the acceptable concentration of feed compo- nents
      polluted by the above norm cesium radionuclide up to 20 times. The alginate
      additives in feed provide almost double decrease in the activity of fish tissues.
      The optimally effective alginate dose should exceed the calcium concentration in
      feed up to 4 times. It was found that utilization of the feedstock (fish meal,
      crops and legumes, oil meal and oil cake) polluted by radionuclides is possible
      in combined aquaculture feed pro- duction. The application of sorbents in feed
      will allow increasing the amount permissible for use of the feed components
      polluted above the norm; ensure the radiation safety of feed and, finally, the
      protection of aquatic biological resources from radioactive contamination. It is
      shown that the sorbent additive in feed is also jus- tified in case of fish
      farming in closed waters affected by radioactive pollution. Feeding by mixed
      fodder with the sorbent additives prevents fish from radionuclide intake from
      natural food sources.

PMID- 25980289
TI  - [Statistical prediction of radioactive contamination impacts on agricultural
      pasture lands].
AB  - Based on the literature data analysis, the rationale is given for the use of
      probabilistic approaches to solve the problems of estimation of a long-lived
      radionuclide uptake in animal products. Methods for statistical prediction of
      radioactive contamination consequences for agricultural pasture lands have been
      devised and implemented in the form of models and program modules. These offer
      the estimation of radionuclide transfer between the links of an agricultural
      chain, taking into account variability in the migration parameters, estimation of
      soil contamination limits based on the preset risk levels for the stuffs produced
      and statistical coordination of standards. An illustration is given of the
      application of the above methods using statistical characteristics of 137Cs
      migration parameters in the soil-plant-animal produce chain. Further trends have
      been formulated in the development of the risk concept as applied to the
      assessment of radioecological situations of radioactive contamination of the
      agricultural land.

PMID- 25980290
TI  - [Content of natural uranium in the lichens and distribution of forms in the soil
      at the coastal area of Lakes Itkul and Sinara of Chelyabinsk region].
AB  - The distribution of natural uranium in soils superaquatic and transeluvial
      positions of the coastal landscape of lakes Itkul and Sinara, and liches on this
      site.The necessity of analysis of the content item in accordance with its form of
      occurrence in the natural environment. The peculiarities of the migration,
      accumulation and distribution of uranium in soils of the mountain areas of the
      watersheds of lakes Itkul and Sinara are found. Identified of specificity species
      lichens on the content of uranium in the substrate.

PMID- 25980292
TI  - [Accumulation and distribution of 137Cs and 90Sr radionuclides in the components
      of water-bottom sediments-macrophytes of Lake Malye Kirpichiky].
AB  - This research work is devoted to analyzing the processes of accumulation and
      distribution of long-lived radionuclides of 90Sr and 137Cs in the components of
      water-sediment-macrophytes of Lake Malye Kirpichiky (Chelyabinsk region). The
      characteristic features of redistribution of radioactive substances, depending on
      the texture of the bottom sediments of the lake and the species composition of
      aquatic vegetation are shown. Also shown is the total stock of radionuclides in
      water and bottom sediments. The coefficients of 90Sr and 137Cs accumulation in
      bottom sediments and macrophytes have been calculated.

PMID- 25980291
TI  - [Radioecological situation in the impact zone of the accidental underground
      nuclear explosion "Kraton-3" in the Republic of Sakha (Yakutia)].
AB  - The paper reports on the results of a ground walking gamma- and gamma
      spectrometric survey made in the impact zone of the accidental underground
      nuclear explosion "Kraton-3". Patterns of migration, 137Cs, 90Sr and Pu
      distribution in the soil-vegetable cover of the northern taiga on permafrost are
      considered. Radioeco- logical situation within the territory surveyed is noted as
      unfavorable.

PMID- 25980293
TI  - [Arterial hypertension in women and cerebrovascular disease].
AB  - Peculiarities of arterial hypertension and development of cerebrovascular disease
      in women are discussed with reference to age-related morbidity features,
      pathogenetic and clinical variants of the disease, its risk factors, and
      approaches to rational pharmacotherapy.

PMID- 25980294
TI  - [Rheumatological syndromes in HIV-infection].
AB  - This review covers publications on rheumatological syndromes associated with HIV
      infection.

PMID- 25980295
TI  - [The basis principles of primary prevention of atherosclerosis].
AB  - Hypolipidemic drugs have a common algorithm of action despite differences in its
      mechanisms. They normalize interaction of cellular receptors with polyenic fatty
      acids (PFA), restore their functional, regulatory and structural action.
      Atherosclerosis is in vivo pathology of individual cells unable to incorporate
      PFA and a syndrome of omega-3 and omega-6 PFA deficiency. Compensatory synthesis
      of humoral mediators (eicosanoids). from endogenous unsaturated omega-9 C 20:3
      dihomo-gamma-linolenic (mead) FA imparts on them non-physiological properties and
      thereby affects in vivo activity of all functional processes and cellular
      functions, forms the multifaceted clinical picture of pathology and
      atheromatosis. Atherosclerosis and atheromatosis are related but different
      processes. Neither statins nor other hypolipidemic drugs exhibit pleiotropic
      action. They normalize active incorporation of PFA that possess intrinsic in vivo
      pleiotropic activity. Omega-3 eicosanoids act as peroxisome proliferators and
      oxidize excess palmitic acid The hypolipidemic action of insulin is mediated
      through transformation of all palmitic FA synthesized from glucose into oleinic
      FA. Hypolipidemic drugs are unsuitable for primary prophylaxis of HLP and
      atherosclerosis that should be based on (a) normalization ofbiological function
      of trophology and biological reaction ofexotrophy, (b) bringing (by substrate
      induction) qualitative and quantitative food composition in correspondence with
      real, rather limited functional capacity of Homo sapiens. Biological function of
      intellect plays an important role in primary prophylaxis of HLP and
      atherosclerosis.

PMID- 25980296
TI  - [The influence of depression on the course of coronary heart disease and quality
      of life].
AB  - We undertook the analysis of cardiovascular risk factors and psycho-social
      factors in 230 patients with coronary heart disease (CHD) based at a city
      polyclinic. Ninety (31.1%) patients suffered depression (19-28 CES-D scores).
      Patients with and without depression were significantly different in terms of
      clinical and functional manifestations of stable angina of effort, cardiovascular
      risk factors, gender; and psycho-social factors. CHD with depression was
      associated with a higher FC of angina of effort, risk of adverse outcome (Duke
      index), frequency of concomitant pathology, psycho-social stress, loss of working
      capacity and a lower income levels. These patients treated with selective
      antidepressants (serotonin reuptake inhibitors) for 6 months experienced a marked
      decrease in the degree of depression and manifestation of its symptoms,
      improvedpsycho- social protection and quality of life compared with untreated
      patients. These data illustrate pathogenetic and behavioural mechanisms
      underlying the relationship between CHD and depression.

PMID- 25980297
TI  - [Results of combined therapy of stable 2-3 FC angina of effort with metabolic
      syndrome including metformin].
AB  - The aim of the study was to evaluate results of combined therapy of stable 2-3 FC
      angina of effort with metabolic syndrome including metformin. Group 1 was
      comprised of 71 patients (38 (53.3%) men and 33 (46.5%) women), group 2 consisted
      of 57 patients treated with isosorbid-5 mononitrate (40 mg/d + amlodipin (5 mg/d)
      + eprosartan (600 mg/d) + thrombo ASS (100 mg/d) + carvedilol (25 mg/d) +
      atorvastatin (20 mg/d). Effects of the treatment were assessed 3, 6, and 12
      months after its onset. At the end of the study, fasting blood glucose, total
      cholesterol, triglyceride, and low density lipoproteide levels decreased by 12.8,
      10.9, 12.9 and 13.6% respectively compared with the initial values (p < 0.01).
      The level of high density lipoproteides increased by 10.4% (p < 0.01).
      Supplementation of therapy with metformin (1000 mg) decreased the frequency of
      episodes of painful and painless myocardial ischemia by 17.0 and 21.1%.
      Simultaneously, tolerance of physical load increased by 22.7%.

PMID- 25980298
TI  - [The quality of life in patients with rheumatoid arthritis treated with
      rituximab].
AB  - The aim of the work was to assess the quality of life in patients with rheumatoid
      arthritis treated with rituximab in combination with methotrexate or methotrexate
      monotherapy. The statistically significant improvement of quality of life in both
      groups 12 months after onset of the treatment was roughly identical. Rutiximab
      was prescribed after ineffective treatment with TNF-alpha inhibitors.

PMID- 25980299
TI  - [Porphyrin metabolism in women with metabolic syndrome].
AB  - A total of 47 women with metabolic syndrome (MS) were examined with the
      fractional determination of porphyrins in urine (uroporphyrin and coproporphyrin)
      and feces (coproporphyrin and protoporphyrin) as well as their precursors (5
      aminolevulinic acid and porphobilinogen). Disorders of porphyrin metabolism were
      documented in 29 (61.7%) women All patients had elevated levels of porphyrin
      precursors. Five women exhibited qualitative changes in the form of abnormal
      ratios of different porphyrin fractions(coproporphyrin/uroporphyrin < 1--0.8 +/-
      0.1 vs normal ratio 3.6 +/- 0.4). 21 patients suffered quantitative changes in
      porphyrin metabolism in the form of manifold increase of porphyrin levels in
      urine and/or feces and formation of biochemical syndromes of secondary
      coproporphyrinuiria, symptomatic rise in porphyrin content in feces, and chronic
      latent hepatic porfiria. Disorders of porphyrin metabolism were associated with
      insulin resistance. Changes of porphyrin metabolism in MS extend the spectrum of
      concomitant disturbances and can be regarded as an additional criterion.

PMID- 25980300
TI  - [Effect of anti-helicobacter therapy on the hepatic glucuronyl transferase system
      of adolescents with Gilbert's syndrome].
AB  - Bilirubin biotransformation occurs with the participation of the glucuronyl
      transferase (GTF) system of the liver and hepatocyte membranes. Disturbances in
      these systems may result in a rise of blood bilirubin levels and disbalance
      between direct and indirect bilirubin leading to jaundice. Gilbert's syndrome
      (GS) is a genetic disorder associated with the enhanced level of indirect
      bilirubin due to GTF insufficiency. MATERIALS AND METHODS: The study included
      adolescents aged 13.4 +/- 0.42 yr divided into 2 groups depending on anti
      Helicobacter therapy (AHBT). We measured levels of direct and indirect
      bilirubins, their ratio, and direct bilirubin content as percentage of total
      bilirubin at admission to and discharge from the hospital. The daily incremental
      growth of both bilirubin fractions was calculated RESULTS: Detailed analysis
      revealed negative effect of AHBT on the GTF system attributable to its impaired
      stability in patients with abnormal genotype. CONCLUSION: Prescription of AHBT to
      children with Gilbert's syndrome requires the thorough choice of medications and
      monitoring of their potential effect on the GFT system.

PMID- 25980301
TI  - [Radiofrequency ablation of focal atrial tachycardia from the right atrial
      appendage].
AB  - The authors report a case of elimination of permanently recurring focal atrial
      tachycardia affecting the right atrial appendage by radiofrequency catheter
      ablation in a 20 year old serviceman.

PMID- 25980303
TI  - 5 ways to strengthen your core. Your company needs to develop strong, capable
      management if it wants to grow. Here's how to do that.

PMID- 25980302
TI  - [A model of primary open-angle glaucoma: manifestations and outcomes].
AB  - OBJECTIVE: To determine the expected duration of the disease and the age of the
      patients with different stages ofprimary open-angle glaucoma complicated by
      pseudoexfoliation syndrome (PES) and/or patients with pseudoexfoliation glaucoma
      (PEG). METHODS: The study protocol included data from 120 patients (50 males
      (41.7%), 70 females (58.3%)); 189 eyes; 102 right eyes; 87 left eyes). The first
      study group (28 patients, 44 eyes) comprised patients with suspected glaucoma.
      The second group (53 patients, 84 eyes) consisted ofpatients with early glaucoma.
      The third group (21 patient, 33 eyes) included patients with advanced glaucoma,
      the forth group (18 patients, 28 eyes) comprised patients with terminal glaucoma.
      Mean age of the patients at diagnosis was 61.6 (58.4; 66.9) years and 66.9 (63.4;
      72.8) years at the endpoint visit in 2013. In all cases, diagnosis was made in
      accordance with the differential diagnostics system and confirmed by special
      diagnostic techniques. The database included data from 3 qualified examinations
      taking account of the results of tonometry and static automated perimetry.
      RESULTS: The mean expected age of the patients age at the onset of blindness was
      75.1 years. The occurrence of the event was limited to a period of 6.1 years.
      Mean age at the time of possible glaucoma development was 59.58 (56.14; 64.36)
      years. The disease itself could develop within 3.24 (-5.38; -1.2) years prior to
      diagnosis. CONCLUSION: Studies for glaucoma diagnosis should be focused on the
      age group of 55-60 years. The degree of IOP reduction in patients with advanced
      glaucoma does not agree with the Russian glaucoma society recommendations which
      accounts for progression of the disease.

PMID- 25980304
TI  - [The historiography of medicine in postwar Germany: a self-examination].
AB  - The paper deals with the history of medical historiography in postwar Germany.
      The two decades after 1945 were crucial for the further development of the
      historiography of medicine in both parts of Germany. Among the issues that need
      to be investigated in more detail are the coming to terms with the Nazi past, the
      ideological rivalry between East and West Germany, and the role of individual
      scientists. The paper invites medical historians to become more deeply engaged
      with the recent history of their field.

PMID- 25980305
TI  - [Paul Diepgen as a senior within his field after 1945].
AB  - Paul Diepgen (1878-1966), professor emeritus in Berlin in 1945, remained a
      leading figure within the field of German medical historians from 1947 onwards in
      his capacity as "guest professor" in Mainz. The present article focuses on two
      areas in which Diepgen was particularly active within his academic field as
      documented in his extensive correspondence: firstly the resumption of contacts
      with emigres and other foreign colleagues which was hampered by Diepgen's
      ambivalent relationship to the National Socialist regime and secondly the
      establishment of the history of medicine as a full academic discipline. Up until
      1961, he continued to nominate his pupils who had been politically "incriminated"
      during the Nazi period for academic positions, but simultaneously encouraged
      younger colleagues and campaigned for the establishment of a comprehensive
      academic degree course in the history of medicine. An examination of the
      confrontation between Diepgen and Werner Leibbrand additionally reveals Diepgen's
      not always uncontroversial concept of the history of medicine.

PMID- 25980306
TI  - [Werner Leibbrand, Annemarie Wettley and controversies on "euthanasia" the
      background of medico-historical and ethical debates in the Post World War II
      era].
AB  - Psychiatrists and medical historians Werner Leibbrand (1896 - 1974) and Annemarie
      Wettley (1913 - 1996) are amongst the most striking figures in the field of
      history of medicine. Leibbrand was appointed director of the "Heil- und
      Pflegeanstalt" in Erlangen shortly after the war. Fuelled by his own experiences
      of suppression and persecution during the Nazi era he promised to unearth the
      crimes and atrocities which had happened under watch of the Nazi regime. He was
      joined by Annemarie Wettley, who worked as a physician at the hospital and had
      developed an increasing interest in the history of medicine. In 1946 they
      published "Um die Menschenrechte der Geisteskranken" ("Human Rights of the
      Mentally Ill") about the "euthanasia" campaign of the Nazi regime. Although a
      number of substantial works followed, Leibbrand and Wettley failed to inform in
      more depth on crimes and atrocities, for instance killings of patients and forced
      malnutrition. Doubts and charges against Wettley regarding her role in dietary
      programmes at the Erlangen hospital and against Leibbrand regarding special
      expert's reports--both had a short-term arrest warrant--might have contributed to
      stagnation in their efforts. In 1953 Leibbrand accepted the offer of a chair at
      the University in Munich, Wettley followed and habilitated in history of
      medicine; in the year 1962 they married. Contacts and exchange amongst medico
      historical experts shed light on developments during the post-war era; still, a
      critical and fundamental review of the crimes within the medical system of the
      Nazi regime did not take place during this time.

PMID- 25980307
TI  - [Between interdependence and separation: the history of medicine as an academic
      discipline in divided Germany (1945-1959)].
AB  - The article traces the development of the history of medicine as an academic
      discipline in divided Germany between 1945 and 1959. During this time period the
      core of the field--the German association for the history of medicine, the
      scientific journal and, as well, many scientists--shifted from East to West
      Germany. The fate of the formerly renowned chair of the history of medicine in
      what was now East Berlin and the difficulties to find a candidate willing to fill
      in the position indicate the problems in establishing a socialist historiography
      of medicine. The 1950s was a lost decade for the historiography of medicine in
      East Germany. In the meantime the historiography of medicine in West Germany,
      based on better starting conditions, consolidated institutionally.

PMID- 25980308
TI  - [The Karl-Sudhoff-Institute in Leipzig and the academic discipline history of
      medicine in the GDR].
AB  - Developmental trends, focus of research and the methods by which work in the
      field of the History of Medicine was organised in the German Democratic Republic
      (East Germany) is presented through the example of the Karl Sudhoff Institute in
      Leipzig, the largest Institute for the study of the History of Medicine in the
      GDR. The article follows the succession of the Directors, and includes, in
      addition to descriptions of research and publishing activities, appendices on the
      work of the Society for the History of Medicine in the German Democratic Republic
      as well as the historical medical collections.

PMID- 25980309
TI  - [Johannes Steudel (1901-1973) as the founder of Bonn medical history].

PMID- 25980310
TI  - The great big question: about really tiny materials.

PMID- 25980312
TI  - Surface Defects on Natural MoS2.
AB  - Transition metal dichalcogenides (TMDs) are being considered for a variety of
      electronic and optoelectronic devices such as beyond complementary metal-oxide
      semiconductor (CMOS) switches, light-emitting diodes, solar cells, as well as
      sensors, among others. Molybdenum disulfide (MoS2) is the most studied of the
      TMDs in part because of its availability in the natural or geological form. The
      performance of most devices is strongly affected by the intrinsic defects in
      geological MoS2. Indeed, most sources of current transition metal dichalcogenides
      have defects, including many impurities. The variability in the electrical
      properties of MoS2 across the surface of the same crystal has been shown to be
      correlated with local variations in stoichiometry as well as metallic-like and
      structural defects. The presence of impurities has also been suggested to play a
      role in determining the Fermi level in MoS2. The main focus of this work is to
      highlight a number of intrinsic defects detected on natural, exfoliated MoS2
      crystals from two different sources that have been often used in previous reports
      for device fabrication. We employed room temperature scanning tunneling
      microscopy (STM) and spectroscopy (STS), inductively coupled plasma mass
      spectrometry (ICPMS), as well as X-ray photoelectron spectroscopy (XPS) to study
      the pristine surface of MoS2(0001) immediately after exfoliation. ICPMS used to
      measure the concentration of impurity elements can in part explain the local
      contrast behavior observed in STM images. This work highlights that the high
      concentration of surface defects and impurity atoms may explain the variability
      observed in the electrical and physical characteristics of MoS2. 

PMID- 25980311
TI  - Perceptions of low-income mothers about the causes and ways to prevent overweight
      in children.
AB  - BACKGROUND: Childhood overweight and obesity remain major health conditions,
      affecting nearly one-third of children in the USA. Multiple factors have been
      identified that contribute to children becoming overweight; however, little is
      known regarding what low-income mothers perceive to be the causes of and the ways
      to prevent children from becoming overweight. METHODS: Low-income mothers (n =
      286) with children aged 4-8 years participated in semi-structured interviews,
      during which they were asked for their opinions about the causes of and ways to
      prevent children from becoming overweight. After themes were identified,
      interviews were coded for the presence or absence of each theme. RESULTS: The
      majority of mothers were non-Hispanic White (69.2%) and overweight or obese
      (77.3%). Additionally, many of the children (41.9%) were overweight or obese. Six
      causes of children becoming overweight were identified by mothers: types or
      quantities of food eaten (90.9%); parenting behaviours (44.9%); lack of activity
      (42.3%); genetics, slow metabolism or medical issues (24.5%); stress or emotion
      (5.2%); and limited access to resources (3.5%). Five ways to prevent children
      from becoming overweight identified by mothers included the following: healthy
      eating (84.9%), more activity (54.8%), limiting screen time (19.9%), limiting
      sugar-sweetened beverages (12.2%) and drinking more water (6.6%). The majority of
      mothers (77.1%) reported that they carried out their suggestions to prevent their
      children from becoming overweight. CONCLUSION: Within this cohort with a high
      prevalence of maternal and child overweight, most mothers identified many of the
      evidence-based strategies for childhood obesity prevention. Future intervention
      development may benefit from focusing on content areas that were less commonly
      identified by mothers as well as helping mothers translate knowledge to
      implementation.

PMID- 25980313
TI  - Lack of exposure of H10N8 avian influenza virus among veterinarians in Guangdong
      Province, China.
AB  - We conducted a retrospective seroepidemiological study for H10N8 avian influenza
      infection among 400 veterinarians sampled from February 2013 to August 2013 in
      Guangdong Province, China. None of the veterinarians had evidence of previous
      infection with the emergent H10N8 AIV. Although there is no evidence of H10N8
      infected veterinarian before the first human index case of H10N8 infection in
      southern China, a more rigorous and long-term surveillance remained essential for
      early warning of novel reassortant viruses and interspecies transmission events.

PMID- 25980314
TI  - A painful lesion of the mandible.

PMID- 25980315
TI  - Directed Assembly of Nucleic Acid-Based Polymeric Nanoparticles from Molecular
      Tetravalent Cores.
AB  - Complementary tetrahedral small molecule-DNA hybrid (SMDH) building blocks have
      been combined to form nucleic acid-based polymeric nanoparticles without the need
      for an underlying template or scaffold. The sizes of these particles can be
      tailored in a facile fashion by adjusting assembly conditions such as SMDH
      concentration, assembly time, and NaCl concentration. Notably, these novel
      particles can be stabilized and transformed into functionalized spherical nucleic
      acid (SNA) structures through the incorporation of capping DNA strands conjugated
      with functional groups. These results demonstrate a systematic, efficient
      strategy for the construction and surface functionalization of well-defined, size
      tunable nucleic acid particles from readily accessible molecular building blocks.
      Furthermore, because these nucleic acid-based polymeric nanoparticles exhibited
      enhanced cellular internalization and resistance to DNase I compared to free
      synthetic nucleic acids, they should have a plethora of applications in
      diagnostics and therapeutics. 

PMID- 25980316
TI  - Circulating mRNA Profiling in Esophageal Squamous Cell Carcinoma Identifies
      FAM84B As A Biomarker In Predicting Pathological Response to Neoadjuvant
      Chemoradiation.
AB  - Esophageal cancer patients with pathological complete response (pCR) to
      neoadjuvant chemoradiation (CRT) have favorable outcomes. Currently, there was no
      reliable biomarker predicting the response to CRT. Perioperative circulating mRNA
      may be associated with prognosis, but its application for predicting treatment
      response is unclear. We prospectively assessed the value of circulating messenger
      RNA (mRNA) profiling in predicting pCR for esophageal squamous cell carcinoma
      (ESCC). Patients with ESCC completing CRT followed by surgery were enrolled for
      analysis. Venous peripheral blood was obtained before and after CRT, and total
      RNA was extracted for hybridization-based whole genome expression analysis and
      quantitative RT-PCR. We found circulating expression profiling was significantly
      altered after CRT. Altered FAM84B expression was significantly predictive of pCR.
      The decrease of serum FAM84B protein level after CRT was also associated with
      pCR. Immunohistochemistry and western blot confirmed that FAM84B protein was
      overexpressed in the majority of patients and ESCC cell lines. Furthermore,
      knockdown of FAM84B delayed tumor growth in ectopic xenografts. We demonstrated
      the decreased of circulating FAM84B mRNA and protein after neoadjuvant CRT may
      predict pCR, and FAM84B protein is overexpressed in ESCC. The potential of FAM84B
      as a novel predictive biomarker, and its biological functions deserve further
      investigation. 

PMID- 25980318
TI  - Increased incidence of Sjogren's syndrome in systemic sclerosis: A nationwide
      population study.
AB  - In the past, there were no studies to evaluate the incidence of Sjogren's
      syndrome and its relationship with sex and age in patients with systemic
      sclerosis. In this study, we enrolled 2217 patients with systemic sclerosis and
      6485 controls from Taiwan's Registry of Catastrophic Illness database and
      National Health Insurance Research Database. Every patient with systemic
      sclerosis was matched to at most three controls by sex, age, month, and year of
      first diagnosis of systemic sclerosis. Standardized incidence ratio (SIR) of
      Sjogren's syndrome in patients with systemic sclerosis and 95% confidence
      interval (95% CI) were calculated. Cox hazard regression was used to calculate
      the hazard ratio (HR). Both male and female patients with systemic sclerosis had
      higher incidences of Sjogren's syndrome (SIR: 7.59, 95% CI = 2.97-19.51; SIR:
      7.59, 95% CI = 5.56-10.42, respectively). The incidence of Sjogren's syndrome in
      patients with systemic sclerosis was still higher compared with control when
      stratified according to age. Age at diagnosis of Sjogren's syndrome was earlier
      in patients with systemic sclerosis in both male and female groups (p = 0.018; p
      < 0.001, respectively). Systemic sclerosis was associated with Sjogren's syndrome
      after adjusting for age, sex, and various autoimmune diseases (HR: 5.98, 95% CI =
      4.79-7.47, p < 0.001). Common cytokines, overlapping antibodies, and similar risk
      alleles were all potential causes of increased incidence of Sjogren's syndrome in
      systemic sclerosis.

PMID- 25980317
TI  - Function-selective domain architecture plasticity potentials in eukaryotic genome
      evolution.
AB  - To help evaluate how protein function impacts on genome evolution, we introduce a
      new concept of 'architecture plasticity potential' - the capacity to form
      distinct domain architectures - both for an individual domain, or more generally
      for a set of domains grouped by shared function. We devise a scoring metric to
      measure the plasticity potential for these domain sets, and evaluate how function
      has changed over time for different species. Applying this metric to a
      phylogenetic tree of eukaryotic genomes, we find that the involvement of each
      function is not random but highly selective. For certain lineages there is strong
      bias for evolution to involve domains related to certain functions. In general
      eukaryotic genomes, particularly animals, expand complex functional activities
      such as signalling and regulation, but at the cost of reducing metabolic
      processes. We also observe differential evolution of transcriptional regulation
      and a unique evolutionary role of channel regulators; crucially this is only
      observable in terms of the architecture plasticity potential. Our findings
      provide a new layer of information to understand the significance of function in
      eukaryotic genome evolution. A web search tool, available at
      http://supfam.org/Pevo, offers a wide spectrum of options for exploring
      functional importance in eukaryotic genome evolution. 

PMID- 25980319
TI  - Hyperventilation in normoxia following myocardial infarction in rats: a shift in
      the set point of the hypoxic ventilatory response.
AB  - AIM: The peripheral chemoreflex is augmented in heart failure, and it may
      contribute to sympathoexcitation. This study aimed to investigate both the
      chemoreflex and the cardiac sympathetic nerve activity in the acute-stage post
      myocardial infarction. METHODS: Myocardial infarction was induced in male adult
      Sprague-Dawley rats by permanent ligation of the left anterior descending
      coronary artery. Within-animal repeated measure assessment of normoxic and
      hypoxic ventilation patterns was determined with whole-body plethysmography and
      compared to sham-operated controls. Cardiac function, morphology and cardiac
      sympathetic nerve activity were determined 14 days later. RESULTS: Infarction
      induced increases in normoxic ventilation through increases in tidal volume
      within 3 days. At the same time points, the hypoxic ventilatory response to short
      durations (10 min) of hypoxia (8, 10 and 12% inspired O2 ) was blunted. At the
      end of the experiment (D14), increases in nerve activity, specifically through
      increased firing rate, and significant cardiac dysfunction (ejection fraction
      43%) were observed in myocardial infarction (MI) group. CONCLUSIONS: An
      augmentation of normoxic ventilation caused by myocardial infarction occurs
      before the amplification of the hypoxic ventilatory response. It occurs much
      earlier following myocardial injury than previously demonstrated and may have a
      role in initiating cardiac sympathoexcitation. The difference in the augmentation
      of hypoxic response between early and late stages post-myocardial infarction
      suggest that the initial change in the chemoreflex is an alteration to the
      operating point of chemoreflex.

PMID- 25980320
TI  - Biomimetic Water-Oxidation Catalysts: Manganese Oxides.
AB  - The catalytic oxidation of water to molecular oxygen is a key process for the
      production of solar fuels. Inspired by the biological manganese-based active site
      for this reaction in the enzyme Photosystem II, researchers have made impressive
      progress in the last decades regarding the development of synthetic manganese
      catalysts for water oxidation. For this, it has been especially fruitful to
      explore the many different types of known manganese oxides MnOx. This chapter
      first offers an overview of the structural, thermodynamic, and mechanistic
      aspects of water-oxidation catalysis by MnOx. The different test systems used for
      catalytic studies are then presented together with general reactivity trends. As
      a result, it has been possible to identify layered, mixed Mn (III/IV)-oxides as
      an especially promising class of bio-inspired catalysts and an attempt is made to
      give structure-based reasons for the good performances of these materials. In the
      outlook, the challenges of catalyst screenings (and hence the identification of a
      "best MnOx catalyst") are discussed. There is a great variety of reaction
      conditions which might be relevant for the application of manganese oxide
      catalysts in technological solar fuel-producing devices, and thus catalyst
      improvements are currently still addressing a very large parameter space.
      Nonetheless, detailed knowledge about the biological catalyst and a solid
      experimental basis concerning the syntheses and water-oxidation reactivities of
      MnOx materials have been established in the last decade and thus this research
      field is well positioned to make important contributions to solar fuel research
      in the future.

PMID- 25980321
TI  - Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in
      Invasive Lobular Versus Ductal Breast Cancer.
AB  - BACKGROUND: This study was conducted to determine the impact of neoadjuvant
      chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed
      for patients with invasive lobular breast carcinoma (ILC) and invasive ductal
      carcinoma (IDC). METHODS: Female patients with a diagnosis of ILC or IDC in The
      Netherlands between July 2008 and December 2012 were identified through the
      population-based Netherlands Cancer Registry. RESULTS: A total of 466 ILC
      patients received NAC compared with 3622 IDC patients. Downstaging by NAC was
      seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC,
      and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these
      patients, respectively (P < 0.0001). Breast-conserving surgery was performed for
      24.4 % of the patients with ILC receiving NAC versus 39.4 % of the patients with
      IDC. In the ILC group, 8.2 % of the patients needed surgical reinterventions
      after BCS due to tumor-positive resection margins compared with 3.4 % of the
      patients with IDC (P < 0.0001). Lobular histology was independently associated
      with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49
      2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more
      often when NAC was administered in ILC as well as IDC. CONCLUSION: The patients
      with ILC receiving NAC were less likely to experience a pCR and less likely to
      undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for
      ILC patients was lower than for patients receiving surgery without NAC. However,
      despite the high number to treating in order to achieve BCS, a small subset of
      ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.

PMID- 25980322
TI  - Inter-patient variability in docetaxel pharmacokinetics: A review.
AB  - Docetaxel is a frequently used chemotherapeutic agent in the treatment of solid
      cancers. Because of the large inter-individual variability (IIV) in the
      pharmacokinetics (PK) of docetaxel, it is challenging to determine the optimal
      dose in individual patients in order to achieve optimal efficacy and acceptable
      toxicity. Despite the established correlation between systemic docetaxel exposure
      and efficacy, the precise factors influencing docetaxel PK are not yet completely
      understood. This review article highlights currently known factors that influence
      docetaxel PK, and focusses on those that are clinically relevant. For example,
      liver impairment should be taken into account when calculating docetaxel dosages
      as this may decrease docetaxel clearance. In addition, drug-drug interactions may
      be of distinct clinical importance when using docetaxel. Particularly, drugs
      strongly inhibiting CYP3A4 such as ketoconazole should not be concurrently
      administered without dose modification, as they may decrease the clearance of
      docetaxel. Gender, castration status, and menopausal status might be of
      importance as potential factors influencing docetaxel PK. The role of
      pharmacogenetics in predicting docetaxel PK is still limited, since no
      polymorphisms of clinical importance have yet been established.

PMID- 25980323
TI  - VEGFR2-Targeted Contrast-Enhanced Ultrasound to Distinguish between Two Anti
      Angiogenic Treatments.
AB  - The aim of this study was to evaluate the capacity of BR55, an ultrasound
      contrast agent specifically targeting vascular endothelial growth factor receptor
      2 (VEGFR2), to distinguish the specific anti-VEGFR2 therapy effect of sunitinib
      from other anti-angiogenic effects of a therapy (imatinib) that does not directly
      inhibit VEGFR2. Sunitinib, imatinib and placebo were administered daily for 11 d
      (264 h) to 45 BalbC mice bearing ectopic CT26 murine colorectal carcinomas.
      During the course of therapy, B-mode ultrasound, contrast-enhanced ultrasound and
      VEGFR2-targeted contrast-enhanced ultrasound were performed to assess tumor
      morphology, vascularization and VEGFR2 expression, respectively. The angiogenic
      effects on these three aspects were characterized using tumor volume, contrast
      enhanced area and differential targeted enhancement. Necrosis, microvasculature
      and expression of VEGFR2 were also determined by histology and immunostaining. B
      Mode imaging revealed that tumor growth was significantly decreased in sunitinib
      treated mice at day 11 (p < 0.05), whereas imatinib did not affect growth.
      Functional evaluation revealed that the contrast-enhanced area decreased
      significantly (p < 0.02) and by similar amounts under both anti-angiogenic
      treatments by day 8 (192 h): -23% for imatinib and -21% for sunitinib. No
      significant decrease was observed in the placebo group. Targeted contrast
      enhanced imaging revealed lower differential targeted enhancement, that is, lower
      levels of VEGFR2 expression, in sunitinib-treated mice relative to placebo
      treated mice from 24 h (p < 0.05) and relative to both placebo- and imatinib
      treated mice from 48 h (p < 0.05). Histologic assessment of tumors after the
      final imaging indicated that necrotic area was significantly higher for the
      sunitinib group (21%) than for the placebo (8%, p < 0.001) and imatinib (11%, p <
      0.05) groups. VEGFR2-targeted ultrasound was able to sensitively differentiate
      the anti-VEGFR2 effect from the reduced area of tumor with functional flow
      produced by both anti-angiogenic agents. BR55 molecular imaging was, thus, able
      both to detect early therapeutic response to sunitinib in CT26 tumors as soon as
      24 h after the beginning of the treatment and to provide early discrimination (48
      h) between tumor response during anti-angiogenic therapy targeting VEGFR2
      expression and response during anti-angiogenic therapy not directly acting on
      this receptor. 

PMID- 25980324
TI  - Midwives in medical student and resident education and the development of the
      medical education caucus toolkit.
AB  - Midwives have been involved formally and informally in the training of medical
      students and residents for many years. Recent reductions in resident work hours,
      emphasis on collaborative practice, and a focus on midwives as key members of the
      maternity care model have increased the involvement of midwives in medical
      education. Midwives work in academic settings as educators to teach the midwifery
      model of care, collaboration, teamwork, and professionalism to medical students
      and residents. In 2009, members of the American College of Nurse-Midwives formed
      the Medical Education Caucus (MECA) to discuss the needs of midwives teaching
      medical students and residents; the group has held a workshop annually over the
      last 4 years. In 2014, MECA workshop facilitators developed a toolkit to support
      and formalize the role of midwives involved in medical student and resident
      education. The MECA toolkit provides a roadmap for midwives beginning involvement
      and continuing or expanding the role of midwives in medical education. This
      article describes the history of midwives in medical education, the development
      and growth of MECA, and the resulting toolkit created to support and formalize
      the role of midwives as educators in medical student and resident education, as
      well as common challenges for the midwife in academic medicine. This article is
      part of a special series of articles that address midwifery innovations in
      clinical practice, education, interprofessional collaboration, health policy, and
      global health. 

PMID- 25980325
TI  - A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and
      IL-10.
AB  - We have previously shown that agonists selective for the cannabinoid receptor 2
      (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro
      correlate of organ graft rejection, predominantly through effects on T-cells.
      Current studies explored the mechanism of this immunosuppression by O-1966 using
      mouse spleen cells. Treatment with O-1966 dose-relatedly decreased levels of the
      active nuclear forms of the transcription factors NF-kappaB and NFAT in wild-type
      T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice. Additionally, a gene
      expression profile of purified T-cells from MLR cultures generated using a PCR T
      cell activation array showed that O-1966 decreased mRNA expression of CD40 ligand
      and CyclinD3, and increased mRNA expression of Src-like-adaptor 2 (SLA2),
      Suppressor of Cytokine Signaling 5 (SOCS5), and IL-10. The increase in IL-10 was
      confirmed by measuring IL-10 protein levels in MLR culture supernatants. Further,
      an increase in the percentage of regulatory T-cells (Tregs) was observed in MLR
      cultures. Pretreatment with anti-IL-10 resulted in a partial reversal of the
      inhibition of proliferation and blocked the increase of Tregs. Additionally, O
      1966 treatment caused a dose-related decrease in the expression of CD4 in MLR
      cultures from wild-type, but not CB2R k/o, mice. These data support the potential
      of CB2-selective agonists as useful therapeutic agents to prolong graft survival
      in transplant patients, and strengthens their potential as a new class of
      immunosuppressive agents with broader applicability. 

PMID- 25980327
TI  - Geographic range size is predicted by plant mating system.
AB  - Species' geographic ranges vary enormously, and even closest relatives may differ
      in range size by several orders of magnitude. With data from hundreds of species
      spanning 20 genera in 15 families, we show that plant species that autonomously
      reproduce via self-pollination consistently have larger geographic ranges than
      their close relatives that generally require two parents for reproduction.
      Further analyses strongly implicate autonomous self-fertilisation in causing this
      relationship, as it is not driven by traits such as polyploidy or annual life
      history whose evolution is sometimes correlated with selfing. Furthermore, we
      find that selfers occur at higher maximum latitudes and that disparity in range
      size between selfers and outcrossers increases with time since their evolutionary
      divergence. Together, these results show that autonomous reproduction--a critical
      biological trait that eliminates mate limitation and thus potentially increases
      the probability of establishment--increases range size.

PMID- 25980326
TI  - Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk
      stratification to prevent futile surgery.
AB  - OBJECTIVES: Appropriate patient selection is important to achieving good outcomes
      and obviating futile surgery in patients with huge (>=10 cm) hepatocellular
      carcinoma (HCC). The aim of this study was to identify independent predictors of
      futile outcomes, defined as death within 3 months of surgery or within 1 year
      from early recurrence following hepatectomy for huge HCC. METHODS: The outcomes
      of 149 patients with huge HCCs who underwent resection during 1995-2012 were
      analysed. Multivariate logistic regression analysis was performed to identify
      preoperative independent predictors of futility. RESULTS: Independent predictors
      of 3-month mortality (18.1%) were: total bilirubin level >34 MUmol/l [P = 0.0443;
      odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR
      5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138).
      The last of these was the sole independent predictor of 1-year recurrence-related
      mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year
      were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer
      (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and
      37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease.
      CONCLUSIONS: According to the present data, among patients submitted to
      hepatectomy for huge HCC, those with a high bilirubin level, low platelet count
      and portal vein thrombosis are at higher risk for futile surgery. The presence of
      portal vein tumour thrombosis should be regarded as a relative contraindication
      to surgery.

PMID- 25980328
TI  - Outcomes of laparoscopic Roux-en-Y gastric bypass in super-super-obese patients.
AB  - BACKGROUND: There is limited outcome data for super-super-obese (SSO) patients,
      those with Body Mass Index (BMI) >= 60 kg/m(2), who seek surgical treatment with
      Laparoscopic Roux-en-Y Gastric Bypass (LRYGB). A large single center LRYGB
      experience was reviewed to compare the safety and efficacy of LRYGB in SSO
      patients to the standard obese population undergoing this procedure. METHODS: The
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) database and an Institutional Review Board approved prospective database
      was used to identify all patients undergoing LRYGB by multiple surgeons at a
      single institution between 1/1/1994 and 11/15/2013. Preoperative co-morbidities,
      postoperative complications, 30-day outcomes, and weight loss at yearly intervals
      were analyzed to determine difference between SSO patients and NonSSO patients
      (BMI < 60 kg/m(2)). RESULTS: Of the 2009 patients undergoing LRYGB over the past
      20 years; 328 had BMI >= 60 kg/m(2). Preoperative co-morbidities, conversion to
      open, and length of stay were significantly increased among SSO patients; however
      there was no significant difference in postoperative outcomes or complications.
      Percent reduction of excess BMI beyond 12 months was significantly improved among
      NonSSO patients with less than 30% follow-up beyond 2 years. CONCLUSIONS: LRYGB
      appears well tolerated for super-super-obese patients with BMI >= 60 kg/m(2) in
      experienced centers. These patients still have significant reduction in excess
      BMI despite being less than NonSSO patients undergoing RYGB. The ACS NSQIP
      database provides excellent tracking of institutional progress with bariatric
      surgical outcomes to facilitate the improvement of best practice techniques.

PMID- 25980329
TI  - Laparoscopic sleeve gastrectomy: long-term weight loss outcomes.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become an increasingly
      popular stand-alone weight loss surgery, but there is a paucity of long-term
      efficacy data. OBJECTIVE: To determine long-term outcomes for patients undergoing
      LSG. SETTING: Tertiary care university hospital in the United States. METHODS:
      This study presents a case series of the first 16 patients undergoing LSG at our
      institution. Inclusion criteria were accepted indications for bariatric surgery,
      and exclusion criteria were any prior bariatric surgery, gastrectomy, substance
      abuse, uncontrolled psychiatric illness, end-stage organ disease, or advanced
      stage cancer. Patients were followed for 7 years. Outcomes included percent
      excess weight loss (%EWL), percent weight loss (%WL), resolution of co
      morbidities, and major and minor complications. RESULTS: Patients enrolled in
      this study had a mean body mass index (BMI) of 43.5 kg/m(2) and a mean age of 49,
      and 14 of 16 patients were women. Fourteen of 16 patients had 7-year follow-ups
      with a mean %WL of 29.6%+/-8.95 and a mean %EWL of 59.6%+/-89.9%. At 7 years, 11
      of 14 patients achieved>50% EWL. One-year follow-up data revealed a mean EWL of
      72%+/-20%, which was significantly greater than the %EWL at 7 years (P = .005).
      Complications included 1 partial obstruction at the gastric incisura angularis
      and 1 subacute leak; both were managed endoscopically. There were no reoperations
      and no deaths. Five of 14 patients experienced new-onset gastroesophageal reflux
      disease. CONCLUSIONS: At 7 years postoperative, the LSG remained a durable and
      successful operation.

PMID- 25980330
TI  - Roux-en-Y gastric bypass attenuates the progression of cardiometabolic
      complications in obese diabetic rats via alteration in gastrointestinal hormones.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes (T2DM)
      and obesity through alteration in gastrointestinal (GI) hormones. OBJECTIVE: The
      objective of this study was to investigate the effect of RYGB on GI hormones and
      cardiometabolic parameters in Zucker diabetic fatty (ZDF) rodents. SETTING:
      Winthrop University Hospital, Research and Academic Center METHODS: Animals were
      divided into 3 groups, pair-fed (n = 4), ad lib (n = 4), and RYGB (n = 5). This
      study was carried out for 4 weeks and all related parameters were measured pre-
      and postsurgery in fasted obese diabetic Zucker rodents. RESULTS:
      Postoperatively, RYGB significantly decreased fasting blood glucose by 32%
      compared with ad lib. Plasma insulin and leptin levels were also found to be
      significantly decreased, by 66% and 38%, respectively, after surgery. Moreover,
      both glucose-dependent insulinotropic polypeptide (GIP) and peptide tyrosine
      tyrosine (PYY) were significantly increased after RYGB-by 300% and 51%,
      respectively. Glucagon-like peptide-1 (GLP-1) levels were also increased, but the
      increase was not statistically significant. Total cholesterol levels of the RYGB
      group remained unchanged for 4 weeks. However, total cholesterol in the ad lib
      and pair-fed groups increased by 25% and 34%, respectively, compared with initial
      levels. The cholesterol/high-density lipoprotein (HDL) ratio was decreased in the
      RYGB group by 14% and 30% compared with the ad lib and pair-fed group,
      respectively. The RYGB group had a significant decrease in aortic wall thickness
      of 25% compared with the ad lib and pair-fed groups. Similarly, the RYGB group
      had a 20-unit (mm Hg) decrease in systolic blood pressure compared with the
      presurgical value. CONCLUSION: RYGB has beneficial cardiometabolic effects
      through alterations in GI hormones in a severely obese and diabetic rodent model.

PMID- 25980331
TI  - Preoperative micronutrient status in morbidly obese patients before undergoing
      bariatric surgery: results of a cross-sectional study.
AB  - BACKGROUND: Reliable information on micronutrient status before bariatric surgery
      is needed to optimize preoperative nutritional status and postoperative
      nutritional therapy. OBJECTIVE: To investigate the pro-/vitamin and mineral
      status and its association with nutrient intake in morbidly obese patients
      seeking bariatric surgery SETTING: Klinikum Vest, Recklinghausen, Germany.
      METHODS: The cross-sectional study investigated retinol, ascorbic acid,
      tocopherol, and beta-carotene (high-pressure liquid chromatography), 25
      hydroxycholecalciferol (enzyme-linked immunosorbent assay), and calcium,
      phosphate, and magnesium (photometry) in serum/plasma in 43 patients (body mass
      index: 52.6+/-10.5 kg/m(2)) before sleeve gastrectomy. Albumin, parathyroid
      hormone, and alkaline phosphatase were analyzed. Data were compared with accepted
      cutoff values. Dietary intake was estimated by 3-day food records, and nutrient
      intake was compared with recommended values. RESULTS: One third of participants
      had ascorbic acid concentrations<28 nmol/L. All patients had beta-carotene
      levels<=.9 umol/L, although retinol was below the cutoff value (<.7 umol/L) in
      only 5%. Tocopherol/cholesterol-ratio was always>2.8 umol/mmol. Of the patients,
      84% had 25-hydroxycholecalciferol levels below 50 nmol/L. Parathyroid hormone was
      elevated in 23% (>6.5 pmol/L). Calcium, magnesium, and alkaline phosphatase were
      always, and phosphate was mostly (98%) above cutoff values. Intake of retinol
      (23%), ascorbic acid (55.8%), vitamin D (90.7%), tocopherol (48.8%), and beta
      carotene (<2.0 mg/d; 37.2%) were often below recommendations. Correlations
      between serum/plasma concentrations and nutritional intake and associations
      between low concentrations and inadequate intake were not observed. CONCLUSIONS:
      Many morbidly obese patients in Germany suffer from deficiencies in multiple
      micronutrients, particularly vitamin D, ascorbic acid, and beta-carotene before
      sleeve gastrectomy. Measurement of preoperative micronutrient status will help
      supplement patients before, and optimize nutritional therapy after, surgery.

PMID- 25980332
TI  - Controversial Issues: When the drugs don't work, can surgery provide a different
      outcome for diabetic adolescents?

PMID- 25980333
TI  - Efficacy and safety of extract of Ginkgo biloba as an adjunct therapy in chronic
      schizophrenia: A systematic review of randomized, double-blind, placebo
      controlled studies with meta-analysis.
AB  - Our study was to review and evaluate the efficacy and safety of extract of Gb
      (EGb) as an adjuvant therapy to antipsychotics in chronic schizophrenia
      treatment. We searched Pubmed/Medline, Embase, PsycINFO, the Cochrane library,
      and especially the Chinese periodical databases. Finally, eight randomized,
      double-blind, placebo-controlled trials (RCTs) of 1033 patients were enrolled,
      with 571 cases in EGb group and 462 in placebo. The result showed that EGb had a
      significant difference in ameliorating total and negative symptoms of chronic
      schizophrenia as an adjuvant therapy to antipsychotics. Thus, the EGb therapy
      plus antipsychotics might be more efficacious. Although the studies describing
      adverse reactions showed no distinguishable difference between EGb and placebo
      group in mean total scores of Treatment Emergent Symptom Scale (TESS) or a Rating
      Scale for Extrapyramidal Side Effects (RSESE), the results of subscores varied in
      different studies. In addition, the severity of side effects of EGb might be
      related to its daily dosage. Therefore, the safety of EGb therapy in chronic
      schizophrenia treatment might need more evidence. And all of these eight trials
      were carried out in China; thus, the results might be restricted to the race and
      we need more high-quality studies of multi-center and randomized double-blind
      clinical trials to compare, analyze, and confirm the findings further. 

PMID- 25980334
TI  - David Triggle: Research collaborations and scientific exchanges with the China
      Pharmaceutical University, Nanjing, China.
AB  - Over the period 1995-2012, David Triggle was a frequent visitor to the China
      Pharmaceutical University in Nanjing, China making many important contributions
      that enhanced the activities of the Research Division of Pharmacology at the
      University. In addition to providing collegial advice and facilitating
      interactions with the international pharmacological community, Professor
      Triggle's international reputation as a thought leader in the field of ion
      channel research and drug discovery provided important insights into the
      potential pathophysiological and therapeutic effects of targeting ion channels.
      This included the L-type calcium channel and the outward delayed rectified
      potassium currents of rapid (IKr) and slow (IKs) components in the myocardium.
      The Nanjing research team had been particularly interested in ion channel
      dysfunction in the context of cardiac arrhythmias, remodeling and drug discovery.
      With Professor Triggle's assistance, the relationship between an increase in
      ICa.L and other biological events including an enhancement of IKr and IKr
      currents, NADPH oxidase and endothelin receptor activation, down regulation of
      calcium modulating protein FKBP12.6, sarco/endoplasmic reticulum Ca(2+)ATPse
      (SERCA2A) and calsequens 2 (CASQ2), calcium leak at the diastole and endoplasmic
      reticulum stress, were evaluated and are discussed. Additionally, the
      organization of several international symposia was greatly enhanced by input from
      Professor Triggle as were the published research manuscripts in international
      pharmacology journals. During his association with the China Pharmaceutical
      University, Professor Triggle aided in enhancing the scientific standing of the
      Pharmacology department and was a highly effective ambassador for international
      research cooperation. 

PMID- 25980336
TI  - Therapeutic Clip Occlusion of the Anterior Choroidal Artery Involved with
      Partially Thrombosed Fusiform Aneurysm: A Case Report.
AB  - BACKGROUND: We describe a rare case with partially thrombosed fusiform anterior
      choroidal artery (AchA) aneurysm successfully treated with therapeutic occlusion
      of the AchA. CLINICAL PRESENTATION: A 58-year-old man presented with transient
      mild hemiparesis of the right side. Magnetic resonance imaging (MRI) showed an
      ischemic lesion in the posterior limb of the left internal capsule. Digital
      subtraction angiography (DSA) revealed a left internal carotid artery saccular
      aneurysm (14.5-mm diameter) arising from the supraclinoid segment. The left AchA
      was not detected in the initial DSA, and MRI showed the aneurysm to be partially
      thrombosed. The second DSA performed 2 weeks after the onset showed
      recanalization of the thrombosed portion of the aneurysm with the left AchA
      apparently arising from its tip. The aneurysm was diagnosed as a partially
      thrombosed fusiform AchA aneurysm. RESULTS: Open surgery was performed and a
      titanium clip was applied to the base of the fusiform aneurysm under motor evoked
      potential monitoring, which remained unchanged after clipping. Occlusion of the
      aneurysm was confirmed by Doppler ultrasound and intraoperative fluorescence
      angiography. Furthermore, Doppler ultrasound and fluorescence angiography showed
      that the blood flow supplying the pyramidal tract was reconstituted by the
      retrograde collateral flow from the choroidal segment. The aneurysm was
      completely obliterated in postoperative DSA, which demonstrated retrograde
      filling of the AchA through the posterior circulation. The patient manifested
      transient weakness of the right side postoperatively, which was completely
      recovered after short-term rehabilitation. CONCLUSIONS: This case illustrates the
      unique clinical course of a rare partially thrombosed fusiform AchA aneurysm,
      successfully treated with therapeutic clip occlusion of the AchA under the
      multimodal monitoring.

PMID- 25980337
TI  - Paradoxical Brain Emboli Related to Heparin-Induced Thrombocytopenia after
      Catheter Ablation.
AB  - BACKGROUND: Thromboembolism associated with catheter ablation of atrial
      fibrillation has been considered to be derived from catheters, ablation sites, or
      a left atrial appendage. Paradoxical brain embolism due to iatrogenic shunt after
      catheter ablation has yet to be described. METHODS: We described a patient with
      atrial fibrillation who developed acute ischemic stroke while coughing 36 hours
      after successful catheter ablation. He had venous thrombosis due to heparin
      induced thrombocytopenia and a right-to-left shunt, likely due to a trans-septal
      puncture during catheter ablation. RESULTS: The final diagnosis was paradoxical
      brain embolism associated with heparin-induced thrombocytopenia. CONCLUSIONS: In
      addition to anticoagulation, we should pay attention to deep venous thrombosis
      including preventive intermittent compression for high-risk patients to reduce
      the risk of stroke after catheter ablation.

PMID- 25980338
TI  - Evaluation of the Differences in the Effects of Antihypertensive Drugs on Blood
      Pressure Variability by 24-Hour Ambulatory Blood Pressure Monitoring in Chronic
      Cerebrovascular Disease.
AB  - BACKGROUND: It has been suggested that antihypertensive drug therapy is
      attributable to the lower blood pressure variability, we investigated the effects
      of 4 classes of antihypertensives on the blood pressure variability; in addition,
      we also compared the effects among 4 calcium channel blockers. METHODS: We
      measured the 24-hour blood pressure variability in 309 patients with a history of
      cerebrovascular disease treated with angiotensin-converting enzyme inhibitor,
      angiotensin receptor blocker, beta blocker, or calcium channel blocker. RESULTS:
      The daytime blood pressure variability treated with beta blockers (14.3 +/- 3.1)
      was higher than that treated with an angiotensin receptor blockers (11.5 +/- 3.1)
      or calcium channel blockers (12.6 +/- 3.4) in patients with cerebrovascular
      disease (P < .05). In the analysis of the patient distribution of blood pressure
      variability, patients receiving beta blockers occurred more frequently in the
      higher blood pressure variability (P = .0023). Treatment with angiotensin
      receptor blockers and cilnidipine, which blocks N-type calcium channels, was
      shown to be more frequently associated with the lower blood pressure variability
      (P = .0202 and .0467). The mean blood pressure of patients grouped by
      distribution of blood pressure variability was found to be independent to blood
      pressure variability, for any of the antihypertensive drugs or calcium channel
      blockers examined. CONCLUSIONS: From the results, it is suggested that
      angiotensin receptor blocker and calcium channel blockers rather than beta
      blockers may be more favorable for blood pressure management in patients with
      cerebrovascular disease. Among the calcium channel blockers, cilnidipine may be
      more favorable than other calcium channel blockers.

PMID- 25980339
TI  - The COMFORT behavioural scale provides a useful assessment of sedation, pain and
      distress in toddlers undergoing minor elective surgery.
AB  - AIM: The COMFORT behavioural scale was developed to assess sedation, pain and
      distress in children unable to report pain. Our aims were to test construct
      validity of the scale in toddlers undergoing minor surgery and determine the
      inter-rater reliability of the scale. METHODS: We consecutively enrolled 45
      children aged 12-36 months from a Norwegian surgical outpatient care unit. The
      level of sedation, pain and distress was assessed before and after surgery with
      the COMFORT behavioural scale. Inter-rater reliability was estimated and
      construct validity was tested based on a priori defined hypotheses. A 2.5-point
      (15%) change in the scale was considered clinically important. RESULTS: We
      obtained 307 scores covering most of the scale's range, but a floor effect was
      clearly present. Inter-rater reliability was high between assessors (intraclass
      correlation coefficient = 0.96; 95% CI 0.92-0.98). Clinically important
      differences were seen between baseline and light sedation (3.1 points, p < 0.001)
      and between light and deep sedation (4.6 points, p = 0.002). The difference
      between baseline and our definition of a pain/distress state was not clinically
      important (1.5 points, p = 0.039). CONCLUSION: The COMFORT behavioural scale can
      provide one aspect of an overall clinical assessment of sedation, and probably
      pain and distress, in toddlers before and after surgery.

PMID- 25980340
TI  - Light-dependent gene activation in Aspergillus nidulans is strictly dependent on
      phytochrome and involves the interplay of phytochrome and white collar-regulated
      histone H3 acetylation.
AB  - The ability for light sensing is found from bacteria to humans but relies only on
      a small number of evolutionarily conserved photoreceptors. A large number of
      fungi react to light, mostly to blue light. Aspergillus nidulans also responds to
      red light using a phytochrome light sensor, FphA, for the control of hundreds of
      light-regulated genes. Here, we show that photoinduction of one light-induced
      gene, ccgA, occurs mainly through red light. Induction strictly depends on
      phytochrome and its histidine-kinase activity. Full light activation also depends
      on the Velvet protein, VeA. This putative transcription factor binds to the ccgA
      promoter in an fphA-dependent manner but independent of light. In addition, the
      blue light receptor LreA binds to the ccgA promoter in the dark but is released
      after blue or red light illumination and together with FphA modulates gene
      expression through histone H3 modification. LreA interacts with the
      acetyltransferase GcnE and with the histone deacetylase HdaA. ccgA induction is
      correlated to an increase of the acetylation level of lysine 9 in histone H3. Our
      results suggest regulation of red light-induced genes at the transcriptional
      level involving transcription factor(s) and epigenetic control through modulation
      of the acetylation level of histone H3. 

PMID- 25980342
TI  - Preliminary data on the effect of osseous anatomy on ex vivo joint mobility in
      the equine thoracolumbar region.
AB  - REASONS FOR PERFORMING STUDY: The thoracolumbar region is clinically important in
      horses; however, the link between joint mobility and bony joint morphology has
      not been tested quantitatively. OBJECTIVES: To establish which aspects of
      vertebral morphology correlate with ex vivo range of motion in the thoracolumbar
      region of Equus caballus, and demonstrate methodologies for linking vertebral
      form and function. STUDY DESIGN: Morphometric study of osteological specimens.
      METHODS: A digital model was created of a disarticulated thoracolumbar region to
      examine bone-to-bone interactions during in silico bending. Linear measurements
      and geometric morphometric landmarks were taken from 6 vertebrae per specimen
      (specimens n = 5, vertebrae n = 30), and compared with experimental range of
      motion in dorsiflexion, ventroflexion, lateroflexion and axial rotation data
      using Spearman's rank correlation, to test a priori hypotheses regarding
      thoracolumbar functional anatomy. RESULTS: Decreased sagittal mobility correlates
      with a tall, heart-shaped vertebral body, although bony interactions restrict
      dorsiflexion more than ventroflexion. Lateroflexion correlates with a narrow
      vertebral body, a short transverse process lever arm, and narrowly placed
      horizontally oriented zygapophyses. Lateral joints also restrict lateroflexion in
      the posterior lumbar region. Axial rotation is related to the shape of the
      zygapophyseal joint. CONCLUSIONS: These preliminary data suggest that vertebral
      joint morphology does determine experimentally measured range of motion, but
      patterns depend upon the type of motion. These methods are useful for identifying
      functionally relevant morphological variation and suggest osteological features
      are important in determining motion.

PMID- 25980341
TI  - Functional analysis of the Arabidopsis thaliana CHLOROPLAST BIOGENESIS 19
      pentatricopeptide repeat editing protein.
AB  - The Arabidopsis thaliana pentatricopeptide repeat (PPR) family of proteins
      contains several degenerate 35-aa motifs named PPR repeats. These proteins
      control diverse post-transcriptional regulatory mechanisms, including RNA
      editing. CLB19 belongs to the PLS subfamily of PPR proteins and is essential for
      the editing and functionality of the subunit A of plastid-encoded RNA polymerase
      (RpoA) and the catalytic subunit of the Clp protease (ClpP1). We demonstrate in
      vitro that CLB19 has a specific interaction with these two targets, in spite of
      their modest sequence similarity. Using site-directed mutagenesis of the rpoA
      target, we analyzed the essential nucleotides required for CLB19-rpoA
      interactions. We verified that, similar to other editing proteins, the C-terminal
      E domain of CLB19 is essential for editing but not for RNA binding. Using
      biomolecular fluorescence complementation, we demonstrated that the E domain of
      CLB19 interacts with the RNA-interacting protein MORF2/RIP2 but not with
      MORF9/RIP9. An interesting finding from this analysis was that overexpression of
      a truncated CLB19 protein lacking the E domain interferes with cell fate during
      megasporogenesis and the subsequent establishment of a female gametophyte,
      supporting an important role of plastids in female gametogenesis. Together these
      analyses provide important clues about the particularities of the CLB19 editing
      protein. 

PMID- 25980343
TI  - Contribution of Deep Microbleeds to Stroke Recurrence: Differences between
      Patients with Past Deep Intracerebral Hemorrhages and Lacunar Infarctions.
AB  - BACKGROUND: This study investigated the contribution of deep cerebral microbleeds
      (MBs) to stroke recurrences in patients with histories of deep intracerebral
      hemorrhages (ICHs) or lacunar infarctions (LIs). METHODS: We prospectively
      analyzed stroke recurrences in patients admitted to our hospital who were treated
      for deep ICHs or LIs between April 2004 and December 2011. The number of deep MBs
      was counted on admission. Stroke recurrence-free rate curves were generated with
      the Kaplan-Meier method using the log-rank test. The odds ratios (ORs) for
      recurrent strokes were derived using multivariate logistic regression models,
      based on deep MBs and risk factors. RESULTS: We evaluated magnetic resonance
      images or the recurrences of 231 deep-ICH patients (92 women, 68.0 +/- 12.0 years
      old) and 309 LI patients (140 women, 70.7 +/- 11.7 years old). The incidences of
      deep ICHs (1.5%/year) and LIs (2.1%/year) presenting as stroke recurrences were
      significantly larger in LI patients with deep MBs than in those without (.01 [P =
      .0001] and .08%/year [P = .005], respectively). However, there was no significant
      difference between deep-ICH patients with and without MBs in terms of incidence
      of recurrences. Multivariate analyses revealed that deep MBs independently and
      significantly elevated the rate of deep ICHs (OR, 19.0; P = .007) or LIs (OR,
      3.62; P = .008) presenting as recurrences in LI patients, but not in deep-ICH
      patients, when adjusted for stroke risk factors. CONCLUSIONS: There may be
      differences between patients with deep ICHs and those with LIs in terms of the
      contribution of deep MBs to stroke recurrence.

PMID- 25980344
TI  - Ultrasound in gynecological cancer: is it time for re-evaluation of its uses?
AB  - Ultrasound is the primary imaging modality in gynecological oncology. Over the
      last decade, there has been a massive technology development which led to a
      dramatic improvement in the quality ultrasound imaging. If performed by an
      experienced sonographer, ultrasound has an invaluable role in the primary
      diagnosis of gynecological cancer, in the assessment of tumor extent in the
      pelvis and abdominal cavity, in the evaluation of the treatment response, and in
      follow-up. Ultrasound is also a valuable procedure for monitoring patients
      treated with fertility-sparing surgery. Furthermore, it is an ideal technique to
      guide tru-cut biopsy for the collection of material for histology. Taking into
      consideration that besides its accuracy, the ultrasound is a commonly available,
      non-invasive, and inexpensive imaging method that can be carried out without any
      risk or discomfort to the patient; it is time to reconsider its role in
      gynecologic oncology and to allocate resources for a specialized education of
      future experts in ultrasound imaging in gynecology. 

PMID- 25980345
TI  - Adjunctive raloxifene treatment improves attention and memory in men and women
      with schizophrenia.
AB  - There is increasing clinical and molecular evidence for the role of hormones and
      specifically estrogen and its receptor in schizophrenia. A selective estrogen
      receptor modulator, raloxifene, stimulates estrogen-like activity in brain and
      can improve cognition in older adults. The present study tested the extent to
      which adjunctive raloxifene treatment improved cognition and reduced symptoms in
      young to middle-age men and women with schizophrenia. Ninety-eight patients with
      a diagnosis of schizophrenia or schizoaffective disorder were recruited into a
      dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover
      trial of adjunctive raloxifene treatment in addition to their usual antipsychotic
      medications. Symptom severity and cognition in the domains of working memory,
      attention/processing speed, language and verbal memory were assessed at baseline,
      6 and 13 weeks. Analyses of the initial 6-week phase of the study using a
      parallel groups design (with 39 patients receiving placebo and 40 receiving
      raloxifene) revealed that participants receiving adjunctive raloxifene treatment
      showed significant improvement relative to placebo in memory and
      attention/processing speed. There was no reduction in symptom severity with
      treatment compared with placebo. There were significant carryover effects,
      suggesting some cognitive benefits are sustained even after raloxifene
      withdrawal. Analysis of the 13-week crossover data revealed significant
      improvement with raloxifene only in attention/processing speed. This is the first
      study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day
      has beneficial effects on attention/processing speed and memory for both men and
      women with schizophrenia. Thus, raloxifene may be useful as an adjunctive
      treatment for cognitive deficits associated with schizophrenia. 

PMID- 25980346
TI  - Mental disorders and risk of suicide attempt: a national prospective study.
AB  - Most mental disorders, when examined independently, are associated with an
      elevated risk for suicide attempt. However, mental disorders often co-occur, and
      that co-occurrence is well explained by models where specific mental disorders
      are understood as manifestations of latent dimensions of psychopathology. To
      date, it remains unclear whether the risk of suicide attempt is due to specific
      mental disorders, to specific dimensions of psychopathology (that is,
      internalizing and externalizing dimensions), to a general psychopathology factor
      or to a combination of these explanations. In a large nationally representative
      prospective survey, the National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC), we used structural equation modeling to examine the shared
      and specific effects of Axis I and Axis II disorders on the occurrence of suicide
      attempts in the general population and among individuals with a lifetime history
      of suicidal ideation. Effects of mental disorders on the risk of suicide attempt
      were exerted almost exclusively through a general psychopathology factor
      representing the shared effect across all mental disorders. Effects of remitted
      psychiatric disorders on the risk of suicide attempt were fully mediated by
      current mental disorders. Similar patterns of associations were found in
      individuals with suicidal ideation. These results held when using different
      approaches to modeling psychiatric comorbidity. Our findings underscore the
      importance of adopting dimensional approaches to comorbidity in the study of
      suicidal behavior. Because mental disorders increase the risk of suicide attempt
      through a general psychopathology liability, this dimension should be considered
      as an important therapeutic target to substantially advance suicide prevention. 

PMID- 25980347
TI  - Diet-induced obese mice retain endogenous leptin action.
AB  - Obesity is characterized by hyperleptinemia and decreased response to exogenous
      leptin. This has been widely attributed to the development of leptin resistance,
      a state of impaired leptin signaling proposed to contribute to the development
      and persistence of obesity. To directly determine endogenous leptin activity in
      obesity, we treated lean and obese mice with a leptin receptor antagonist. The
      antagonist increased feeding and body weight (BW) in lean mice, but not in obese
      models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In
      contrast, the antagonist increased feeding and BW comparably in lean and diet
      induced obese (DIO) mice, an increase associated with decreased hypothalamic
      expression of Socs3, a primary target of leptin. These findings demonstrate that
      hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean
      mice and counter the view that resistance to endogenous leptin contributes to the
      persistence of DIO in mice. 

PMID- 25980348
TI  - snoRNA U17 regulates cellular cholesterol trafficking.
AB  - Cholesterol is required for the growth and viability of mammalian cells and is an
      obligate precursor for steroid hormone synthesis. Using a loss-of-function screen
      for mutants with defects in intracellular cholesterol trafficking, a Chinese
      hamster ovary cell mutant with haploinsufficiency of the U17 snoRNA was isolated.
      U17 is an H/ACA orphan snoRNA, for which a function other than ribosomal
      processing has not previously been identified. Through expression profiling, we
      identified hypoxia-upregulated mitochondrial movement regulator (HUMMR) mRNA as a
      target that is negatively regulated by U17 snoRNA. Upregulation of HUMMR in U17
      snoRNA-deficient cells promoted the formation of ER-mitochondrial contacts,
      decreasing esterification of cholesterol and facilitating cholesterol trafficking
      to mitochondria. U17 snoRNA and HUMMR regulate mitochondrial synthesis of
      steroids in vivo and are developmentally regulated in steroidogenic tissues,
      suggesting that the U17 snoRNA-HUMMR pathway may serve a previously unrecognized,
      physiological role in gonadal tissue maturation. 

PMID- 25980350
TI  - Optimization of dosing regimens and dosing in special populations.
AB  - Treatment of infectious diseases is becoming increasingly challenging with the
      emergence of less-susceptible organisms that are poorly responsive to existing
      antibiotic therapies, and the unpredictable pharmacokinetic alterations arising
      from complex pathophysiologic changes in some patient populations. In view of
      this fact, there has been a progressive work on novel dose optimization
      strategies to renew the utility of forgotten old antibiotics and to improve the
      efficacy of those currently in use. This review summarizes the different
      approaches of optimization of antibiotic dosing regimens and the special patient
      populations which may benefit most from these approaches. The existing methods
      are based on monitoring of antibiotic concentrations and/or use of clinical
      covariates. Measured concentrations can be correlated with predefined
      pharmacokinetic/pharmacodynamic targets to guide clinicians in predicting the
      necessary dose adjustment. Dosing nomograms are also available to relate observed
      concentrations or clinical covariates (e.g. creatinine clearance) with optimal
      dosing. More precise dose prediction based on observed covariates is possible
      through the application of population pharmacokinetic models. However, the most
      accurate estimation of individualized dosing requirements is achieved through
      Bayesian forecasting which utilizes both measured concentration and clinical
      covariates. Various software programs are emerging to ease clinical application.
      Whilst more studies are warranted to clarify the clinical outcomes associated
      with the different dose optimization approaches, severely ill patients in the
      course of marked infections and/or inflammation including those with sepsis,
      septic shock, severe trauma, burns injury, major surgery, febrile neutropenia,
      cystic fibrosis, organ dysfunction and obesity are those groups which may benefit
      most from individualized dosing. 

PMID- 25980349
TI  - Phylogenomics of Mycobacterium Nitrate Reductase Operon.
AB  - NarGHJI operon encodes a nitrate reductase that can reduce nitrate to nitrite.
      This process enhances bacterial survival by nitrate respiration under anaerobic
      conditions. NarGHJI operon exists in many bacteria, especially saprophytic
      bacteria living in soil which play a key role in the nitrogen cycle. Most
      actinomycetes, including Mycobacterium tuberculosis, possess NarGHJI operons. M.
      tuberculosis is a facultative intracellular pathogen that expands in macrophages
      and has the ability to persist in a non-replicative form in granuloma lifelong.
      Nitrogen and nitrogen compounds play crucial roles in the struggle between M.
      tuberculosis and host. M. tuberculosis can use nitrate as a final electron
      acceptor under anaerobic conditions to enhance its survival. In this article, we
      reviewed the mechanisms regulating nitrate reductase expression and affecting its
      activity. Potential genes involved in regulating the nitrate reductase expression
      in M. tuberculosis were identified. The conserved NarG might be an alternative
      mycobacterium taxonomic marker. 

PMID- 25980351
TI  - Dynamics of adaptive and innate immunity in patients treated during primary human
      immunodeficiency virus infection: results from Maraviroc in HIV Acute Infection
      (MAIN) randomized clinical trial.
AB  - We evaluated the dynamics of innate and adaptive immunity in patients treated
      with combined antiretroviral therapy (cART) during primary human immunodeficiency
      virus infection (PHI), enrolled in a prospective randomized trial (MAIN, EUDRACT
      2008-007004-29). After 48 weeks of cART, we documented a reduction in activated B
      cells and CD8(+) T cells. Natural killer cell and dendritic cell frequencies were
      measured and a decrease in CD16(+) CD56(dim) with a reciprocal rise in CD56(high)
      natural killer cells and an increase in myeloid and plasmacytoid dendritic cells
      were recorded. In conclusion, 48 weeks of cART during PHI showed significant
      benefits for both innate and adaptive immunity. 

PMID- 25980352
TI  - Prevalence of Shiga toxin-producing Shigella species isolated from French
      travellers returning from the Caribbean: an emerging pathogen with international
      implications.
AB  - Shiga toxins (Stxs) are potent cytotoxins that inhibit host cell protein
      synthesis, leading to cell death. Classically, these toxins are associated with
      intestinal infections due to Stx-producing Escherichia coli or Shigella
      dysenteriae serotype 1, and infections with these strains can lead to haemolytic
      uraemic syndrome. Over the past decade, there has been increasing recognition
      that Stx is produced by additional Shigella species. We recently reported the
      presence and expression of stx genes in Shigella flexneri 2a clinical isolates.
      The toxin genes were carried by a new stx-encoding bacteriophage, and infection
      with these strains correlated with recent travel to Haiti or the Dominican
      Republic. In this study, we further explored the epidemiological link to this
      region by utilizing the French National Reference Centre for Escherichia coli,
      Shigella and Salmonella collection to survey the frequency of Stx-producing
      Shigella species isolated from French travellers returning from the Caribbean.
      Approximately 21% of the isolates tested were found to encode and produce Stx.
      These isolates included strains of S. flexneri 2a, S. flexneri Y, and S.
      dysenteriae 4. All of the travellers who were infected with Stx-producing
      Shigella had recently travelled to Haiti, the Dominican Republic, or French
      Guiana. Furthermore, whole genome sequencing showed that the toxin genes were
      encoded by a prophage that was highly identical to the phage that we identified
      in our previous study. These findings demonstrate that this new stx-encoding
      prophage is circulating within that geographical area, has spread to other
      continents, and is capable of spreading to multiple Shigella serogroups.

PMID- 25980354
TI  - HIV encephalitis related to the development of a discordant resistant virus in
      CNS.

PMID- 25980353
TI  - Development of two real-time multiplex PCR assays for the detection and
      quantification of eight key bacterial pathogens in lower respiratory tract
      infections.
AB  - The frequent lack of a positive and timely microbiological diagnosis in patients
      with lower respiratory tract infection (LRTI) is an important obstacle to
      antimicrobial stewardship. Patients are typically prescribed broad-spectrum
      empirical antibiotics while microbiology results are awaited, but, because these
      are often slow, negative, or inconclusive, de-escalation to narrow-spectrum
      agents rarely occurs in clinical practice. The aim of this study was to develop
      and evaluate two multiplex real-time PCR assays for the sensitive detection and
      accurate quantification of Streptococcus pneumoniae, Haemophilus influenzae,
      Staphylococcus aureus, Moraxella catarrhalis, Escherichia coli, Klebsiella
      pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We found that
      all eight bacterial targets could be reliably quantified from sputum specimens
      down to a concentration of 100 CFUs/reaction (8333 CFUs/mL). Furthermore, all 249
      positive control isolates were correctly detected with our assay, demonstrating
      effectiveness on both reference strains and local clinical isolates. The
      specificity was 98% on a panel of nearly 100 negative control isolates. Bacterial
      load was quantified accurately when three bacterial targets were present in
      mixtures of varying concentrations, mimicking likely clinical scenarios in LRTI.
      Concordance with culture was 100% for culture-positive sputum specimens, and 90%
      for bronchoalveolar lavage fluid specimens, and additional culture-negative
      bacterial infections were detected and quantified. In conclusion, a quantitative
      molecular test for eight key bacterial causes of LRTI has the potential to
      provide a more sensitive decision-making tool, closer to the time-point of
      patient admission than current standard methods. This should facilitate de
      escalation from broad-spectrum to narrow-spectrum antibiotics, substantially
      improving patient management and supporting efforts to curtail inappropriate
      antibiotic use.

PMID- 25980355
TI  - From the monovalent to the nine-valent HPV vaccine.
AB  - An investigational monovalent human papillomavirus (HPV) 16 virus-like particle
      vaccine has been shown to prevent persistent infection and cervical disease
      related to HPV 16 and was proof of concept (2002). Designed to prevent the bulk
      of invasive cervical cancer, quadrivalent (HPV 6/11/16/18) and bivalent (HPV
      16/18) vaccines have been available since 2006 and 2007, respectively. They are
      highly effective in preventing HPV 16/18-related cervical precancer; the
      quadrivalent version also prevents genital warts related to HPV 6/11. It has been
      shown that the precursors of vulvar, vaginal and anal cancer related to the
      vaccine types are effectively prevented. This led to a paradigm shift from a
      female-only cervical cancer vaccine to a vaccine for the prevention of HPV
      related disease and cancer for both sexes. Vaccination before the start of sexual
      activity is most effective, and consequently most programs target 9- to 12-year
      olds. Additionally, recent studies have proven the noninferior immunoresponse of
      a two-dose schedule in these age cohorts. Gender-neutral vaccination has become
      more common; it improves coverage and also provides protection to all males.
      Recently a nine-valent HPV vaccine (HPV 6/11/16/18/31/33/45/52/58) was licensed;
      it provides high and consistent protection against infections and diseases
      related to these types, with ~90% of cervical and other HPV-related cancers and
      precancers potentially being avoided. Coverage is key. Efforts must be made to
      provide HPV vaccination in low-resource countries that lack screening programs.
      In countries with cervical cancer screening, HPV vaccination will greatly affect
      screening algorithms.

PMID- 25980356
TI  - Risk factors and outcome for colistin-resistant Acinetobacter nosocomialis
      bacteraemia in patients without previous colistin exposure.
AB  - The clinical characteristics of patients with colistin-resistant Acinetobacter
      baumannii bacteraemia have been documented, but those of patients with
      bacteraemia caused by other Acinetobacter species remain unknown. Previous
      exposure to colistin has been shown to be associated with the emergence of
      colistin resistance, but may be not the only predisposing factor. In the current
      study, we highlight the risk and outcome of patients without previous exposure to
      colistin who acquired colistin-resistant Acinetobacter nosocomialis (ColRAN)
      bacteraemia. This 11-year single-centre retrospective study analysed 58 patients
      with ColRAN bacteraemia and 213 patients with colistin-susceptible A.
      nosocomialis (ColSAN) bacteraemia. Antimicrobial susceptibilities were determined
      with an agar dilution method. The clonal relationship of ColRAN isolates was
      determined with pulsed-field gel electrophoresis. A conjugation mating-out assay
      was conducted to delineate the potential transfer of colistin resistance genes.
      Multivariable analysis was performed to evaluate the risk factors for ColRAN
      bacteraemia. Chronic obstructive pulmonary disease (COPD) was independently
      associated with ColRAN bacteraemia (OR 3.04; 95% CI 1.45-6.37; p 0.003). Patients
      with ColRAN bacteraemia had higher APACHE II scores, but the two groups showed no
      significant differences in 14-day mortality (10.3% vs. 10.3%) or 28-day mortality
      (15.5% vs. 15.0%). ColRAN isolates had greater resistance than ColSAN isolates to
      all antimicrobial agents except for ciprofloxacin (0% vs. 6.6%). There were 16
      different ColRAN pulsotypes, and two major clones were found. Colistin resistance
      did not transfer to colistin-susceptible A. baumannii or A. nosocomialis. These
      results show that COPD is an independent risk factor for acquisition of ColRAN
      bacteraemia. The mortality rates were similar between patients with ColRAN and
      ColSAN bacteraemia.

PMID- 25980357
TI  - Cytotoxicity of thermo-responsive polymeric nanoparticles based on N
      isopropylacrylamide for potential application as a bioscaffold.
AB  - Polymeric nanoparticles based on poly-N-isopropylacrylamide (pNiPAM NPs) and
      their bio-medical applications have been widely investigated in recent years.
      These tunable nanoparticles are considered to be great candidates for drug
      delivery systems, biosensors and bioanalytical devices. Thus, the
      biocompatibility and toxicity of these nanoparticles is clearly a crucial issue.
      In this work, the cytotoxicity of thermo-responsive pNiPAM nanoparticles was
      studied, followed by a detailed analysis of the NPs morphology in growing cell
      cultures and their 3D structure. Cytotoxic examination was conducted for two cell
      cultures - HeLa (cervical cancer cell line) and HeK293 (human embryonic kidney
      cell line), employing MTT (3-4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium
      bromide) assay and viability tests. We used Cryo-SEM (scanning electron
      microscopy) and fluorescence microscopy (IN Cell Analyzer) in order to
      investigate the morphological structure of the polymer network. We show that
      pNiPAM nanoparticles do not exhibit any cytotoxicity effects on the investigated
      cell lines. Additionally, we report that the pNiPAM nanoparticle based scaffold
      promotes cell growth. 

PMID- 25980358
TI  - Exenatide (a GLP-1 agonist) improves the antioxidative potential of in vitro
      cultured human monocytes/macrophages.
AB  - Macrophages are dominant cells in the pathogenesis of atherosclerosis. They are
      also a major source of reactive oxygen species (ROS). Oxidative stress, which is
      particularly high in subjects with diabetes, is responsible for accelerated
      atherosclerosis. Novel antidiabetic drugs (e.g., glucagon-like peptide-1 (GLP-1)
      agonists) were shown to reduce ROS level. Therefore, we conceived a study to
      evaluate the influence of exenatide, a GLP-1 agonist, on redox status in human
      monocytes/macrophages cultured in vitro, which may explain the beneficial effects
      of incretin-based antidiabetic treatment. Human macrophages obtained from 10
      healthy volunteers were in vitro subjected to the treatment with GLP-1 agonist
      (exenatide) in the presence of lipopolysaccharide (LPS), antagonist of GLP-1
      receptors (exendin 9-39), or protein kinase A inhibitor (H89). Afterwards,
      reactive oxygen species, malondialdehyde level, NADPH oxidase, and antioxidative
      enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and
      catalase] expression was evaluated. Finally, we estimated the activity of the
      abovementioned enzymes in the presence of H89. According to our findings,
      exenatide reduced ROS and malondialdyhyde (MDA) level by decreasing the
      expression of ROS-generating NADPH oxidase and by increasing the expression and
      activities of SOD and GSH-Px. We also showed that this effect was significantly
      inhibited by exendin 9-39 (a GLP-1 antagonist) and blocked by H89. Exenatide
      improved the antioxidative potential and reduced oxidative stress in cultured
      human monocytes/macrophages, and this finding may be responsible for the
      pleiotropic effects of incretin-based therapies. This effect relied on the
      stimulation of GLP-1 receptor. 

PMID- 25980359
TI  - The actions of prolonged exposure to cholinergic agonists on isolated bladder
      strips from the rat.
AB  - The present study was done to explore the cholinergic systems operating in the
      wall of the isolated rat bladder. In a first set of experiments, bladder strips
      in vitro were subjected to cumulative concentration-response curve (CRC) to non
      selective muscarine agonist carbachol or the partially M2>M3 selective agonist
      arecaidine to establish optimal concentration to be used thereafter. In a second
      set of experiments, the effects of drugs (solifenacin, isoproterenol, and
      mirabegron) were tested on urinary bladder contraction induced by the non
      selective muscarinergic agonist carbachol. For both agonists, the contractile
      responses are qualitatively similar: an initial transient rise in tension
      followed by complex bursts of high-frequency small 'micro'-contractions
      superposed on a tonic contraction, with immediate transient 'rebound' contraction
      after the agonist is washed from the preparation. This rebound contraction is
      greater with carbachol than arecaidine. Components of the responses to
      cholinergic stimulation, notably the micro-contractions, were found to be
      differently stimulated and inhibited by the M3>M2 selective antagonist
      solifenacin and by the beta-adrenoceptor agonists isoprenaline and mirabegron. A
      physiological role for the muscarinic dependent phasic contractions and the micro
      anatomical elements that might be involved are not known but may be related to
      non-voiding activity observed during filling cystometry in conscious animals
      related to afferent discharge and possibly sensation. Furthermore, suggestions
      for the potential impact of these findings and design of further studies in
      relation to bladder physiology, pharmacology, and pathology are discussed. 

PMID- 25980360
TI  - How can proteomics elucidate the complexity of multiple sclerosis?
AB  - Multiple sclerosis affects more than 2.5 million people worldwide. Although
      multiple sclerosis was described almost 150 years ago, there are many knowledge
      gaps regarding its etiology, diagnosis, prognosis, and pathogenesis. Multiple
      sclerosis is an inflammatory, demyelinating, neurodegenerative disease of the
      CNS. During the last several decades, experimental models of multiple sclerosis
      have contributed to our understanding of the inflammatory disease mechanisms and
      have aided drug testing and development. However, little is known about the
      neurodegenerative mechanisms that operate during the evolution of the disease.
      Currently, all therapeutic approaches are primarily based on the inflammatory
      aspect of the disease. During the last decade, proteomics has emerged as a
      promising tool for revealing molecular pathways as well as identifying and
      quantifying differentially expressed proteins. Therefore, proteomics may be used
      for the discovery of biomarkers, potential drug targets, and new regulatory
      mechanisms. To date, a considerable number of proteomics studies have been
      conducted on samples from experimental models and patients with multiple
      sclerosis. These data form a solid base for further careful analysis and
      validation. 

PMID- 25980361
TI  - Fiber heart valve prosthesis: Early in vitro fatigue results.
AB  - Transcatheter aortic valve replacement has become today a largely considered
      alternative technique to surgical valve replacement in patients with high risk
      for open chest surgery. Biological valve tissue used in the transcatheter devices
      has shown success over 5 years now, but the procedure remains expensive.
      Moreover, different studies point out potential degradations that the tissue can
      undergo when folded to lower diameter and released in calcified environment with
      irregular geometry, which may jeopardize the durability of the device. The use of
      synthetic materials, like textile in particular, to replace biological valve
      leaflets would help reducing the procedure costs, and limit the degradations when
      the valve is crimped. Textile polyester material has been extensively used in the
      vascular surgery and is characterized by outstanding folding and strength
      properties combined with proven biocompatibility. However, the friction effects
      that occur between filaments and between yarns within a fabric under flexure
      loading could be critical for the resistance of the material on the long term.
      The purpose of this study was to assess the early fatigue performances of textile
      valve prototypes under accelerated cyclic loading up to 200 Mio cycles.
      Durability tests show that the fibrous material undergoes rearrangements between
      fibrous elements within the textile construction and the mechanical properties
      are modified on the long term. But testing is not complete with 200 Mio cycles.
      The material should be tested up to a higher number of cycles in future work to
      test the effective long-term durability. (c) 2015 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 104B: 986-992, 2016.

PMID- 25980362
TI  - Palygorskite changes heavy metal bioavailability and microbial functional
      diversity in sewage sludge composting.
AB  - To investigate the effects of palygorskite on chemical forms of heavy metal and
      microbial functional diversity in the sewage sludge composting, a compost matrix
      of sewage sludge, wheat straw and varying contents of palygorskite were
      inoculated with the compound microbial preparation. The chemical speciation
      analysis by a Community Bureau of Reference-sequential extraction indicated the
      contribution of palygorskite to reduce the bioavailability of a model metal, Cu,
      during the composting process. The Biolog EcoPlate(TM) test revealed that the
      microbial community showed better capability of utilizing complex macro-molecules
      (such as miscellaneous and polymers) in the presence of palygorskite. Increasing
      the palygorskite contents from 1% to 5%, the microbial activity showed an
      increasing tendency. However, continuously increasing the palygorskite resulted
      in a decline of the microbial metabolism. Therefore, appropriate content of
      palygorskite is an ideal additive for composting, not only enhancing the
      microbial activity, but also reducing the metal toxicity. 

PMID- 25980364
TI  - Purification of transferrin by magnetic immunoaffinity beads.
AB  - Immunoaffinity adsorbent for transferrin (Tf) purification was prepared by
      immobilizing anti-transferrin (Anti-Tf) antibody on magnetic
      monosizepoly(glycidyl methacrylate) beads, which were synthesized by dispersion
      polymerization technique in the presence of Fe3 O4 nanopowder and obtained with
      an average size of 2.0 MUm. The magnetic poly(glycidyl methacrylate) (mPGMA)
      beads were characterized by Fourier transform infrared spectroscopy, swelling
      tests, scanning electron microscopy, electron spin resonance spectroscopy,
      thermogravimetric analysis and zeta sizing analysis. The density and swelling
      ratio of the beads were 1.08 g/cm(3) and 52%, respectively. Anti-Tf molecules
      were covalently coupled through epoxy groups of mPGMA. Optimum binding of anti-Tf
      was 2.0 mg/g. Optimum Tf binding from aqueous Tf solutions was determined as 1.65
      mg/g at pH 6.0 and initial Tf concentration of 1.0 mg/mL. There was no remarkable
      loss in the Tf adsorption capacity of immunoaffinity beads after five adsorption
      desorption cycles. Tf adsorption from artificial plasma was also investigated and
      the purity of the Tf molecules was shown with gel electrophoresis studies. 

PMID- 25980363
TI  - ato-Gal4 fly lines for gene function analysis: Eya is required in late
      progenitors for eye morphogenesis.
AB  - The Gal4/UAS system is one of the most powerful tools for the study of cellular
      and developmental processes in Drosophila. Gal4 drivers can be used to induce
      targeted expression of dominant-negative and dominant-active proteins,
      histological markers, activity sensors, gene-specific dsRNAs, modulators of cell
      survival or proliferation, and other reagents. Here, we describe novel atonal
      Gal4 lines that contain regions of the regulatory DNA of atonal, the proneural
      gene for photoreceptors, stretch receptors, auditory organ, and some olfactory
      sensilla. During neurogenesis, the atonal gene is expressed at a critical
      juncture, a time of transition from progenitor cell to developing neuron. Thus,
      these lines are particularly well suited for the study of the transcription
      factors and signaling molecules orchestrating this critical transition. To
      demonstrate their usefulness, we focus on two visual organs, the eye and the
      Bolwig. We demonstrate the induction of predicted eye phenotypes when expressing
      the dominant-negative EGF receptor or a dsRNA against Notch in the developing eye
      disc. In another example, we show the deletion of the Bolwig's organ using the
      proapoptotic factor Hid. Finally, we investigate the function of the eye
      specification factor Eyes absent or Eya in late retinal progenitors, shortly
      before they begin morphogenesis. We show that Eya is still required in these late
      progenitors to promote eye formation, and show failure to induce the target gene
      atonal and consequent lack of neuron formation.

PMID- 25980365
TI  - Results of the Minnesota Multiphasic Personality Inventory-2 among gestational
      surrogacy candidates.
AB  - OBJECTIVE: To obtain normative data on the Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2) personality test for gestational surrogate (GS) candidates.
      METHODS: A retrospective study was undertaken through chart review of all GS
      candidates assessed at Shady Grove Fertility Center, Rockville, MD, USA, between
      June 2007 and December 2009. Participants completed the MMPI-2 test during
      screening. MMPI-2 scores, demographic information, and screening outcome were
      retrieved. RESULTS: Among 153 included candidates, 132 (86.3%) were accepted to
      be a GS, 6 (3.9%) were ruled out because of medical reasons, and 15 (9.8%) were
      ruled out because of psychological reasons. The mean scores on each of the MMPI-2
      scales were within the normal range. A score of more than 65 (the clinical
      cutoff) was recorded on the L scale for 46 (30.1%) candidates, on the K scale for
      61 (39.9%), and on the S scale for 84 (54.9%). Women who were ruled out for
      psychological reasons had significantly higher mean scores on the validity scales
      F and L, and on clinical scale 8 than did women who were accepted (P<0.05 for
      all). CONCLUSION: Most GS candidates are well adjusted and free of
      psychopathology, but candidates tend to present themselves in an overly positive
      way.

PMID- 25980366
TI  - The effect of economic downturns on maternal mortality among pregnancies with
      abortive outcomes in 81 countries, 1981-2010.
AB  - OBJECTIVE: To determine the association between economic downturns and abortion
      related maternal mortality in multiple countries over 30 years. METHODS: In a
      retrospective study, WHO data were obtained for maternal deaths among pregnancies
      with abortive outcomes between January 1, 1981, and December 31, 2010. Economic
      data for the same period were obtained from The World Bank. An economic downturn
      was defined as an annual decline in gross domestic product per head. Multivariate
      regression-controlling for country-specific differences in infrastructure,
      population size, and demographic structure-and 5-year lag analyses were
      performed. RESULTS: Data were available for 81 countries. Abortion-related
      maternal mortality was significantly increased in years of economic downturns
      (R=0.0708; 95% confidence interval [CI] 0.0264-0.1151; P=0.0018). The association
      was sustained for 4 years after an economic downturn (year 1: R=0.0709 [95% CI
      0.0231-0.1187], P=0.0037; year 2: R=0.0634 [0.0178-0.1089], P=0.0065; year 3:
      R=0.0554 [0.0105-0.1004], P=0.0157; year 4: R=0.0593 [0.0148-0.1037], P=0.009).
      There was an annual 36% increase in deaths associated with unsafe abortion during
      economic downturn years. CONCLUSION: Economic downturns were associated with
      increased abortion-related maternal mortality, possibly due to changes in
      government healthcare spending and service provision. A global economic downturn
      could impede a reduction in maternal mortality.

PMID- 25980367
TI  - Estimating the uptake of maternal syphilis screening and other antenatal
      interventions before and after national rollout of syphilis point-of-care testing
      in Ghana.
AB  - OBJECTIVE: To compare the uptake of maternal syphilis and HIV screening,
      intermittent preventive treatment for malaria, and tetanus toxoid administration
      in three regions of Ghana, before and after the rollout of syphilis point-of-care
      tests (POCTs). METHODS: Antenatal register records were reviewed in 15 selected
      health facilities over an eight-month period, 16 months apart. Register records
      had been evaluated using the maternal record booklets as a gold standard in a
      separate prior survey. RESULTS: In the evaluation study, the sensitivity of
      register data was low, ranging from 33.3% for tetanus toxoid administration to
      53.8% for syphilis serology. In total, 8282 antenatal client records (4141 in
      each period) were reviewed. Less than a third of pregnant women received any
      single intervention at either period (ranging from 17.8% for tetanus toxoid to
      29.8% for HIV testing). Overall, HIV screening had a marginal absolute increase
      of about 2% while the remaining interventions experienced non-significant
      absolute decreases of 4.1 to 11.1%. When adjusting for under-recording, syphilis
      screening uptake was 50% before and 33.6% after the introduction of POCTs.
      CONCLUSION: Use of POCTs for syphilis did not result in increased uptake. Routine
      monitoring of antenatal interventions using the antenatal register may result in
      underestimation of their uptake.

PMID- 25980368
TI  - A novel mixed integer programming for multi-biomarker panel identification by
      distinguishing malignant from benign colorectal tumors.
AB  - Multi-biomarker panels can capture the nonlinear synergy among biomarkers and
      they are important to aid in the early diagnosis and ultimately battle complex
      diseases. However, identification of these multi-biomarker panels from case and
      control data is challenging. For example, the exhaustive search method is
      computationally infeasible when the data dimension is high. Here, we propose a
      novel method, MILP_k, to identify serum-based multi-biomarker panel to
      distinguish colorectal cancers (CRC) from benign colorectal tumors. Specifically,
      the multi-biomarker panel detection problem is modeled by a mixed integer
      programming to maximize the classification accuracy. Then we measured the serum
      profiling data for 101 CRC patients and 95 benign patients. The 61 biomarkers
      were analyzed individually and further their combinations by our method. We
      discovered 4 biomarkers as the optimal small multi-biomarker panel, including
      known CRC biomarkers CEA and IL-10 as well as novel biomarkers IMA and NSE. This
      multi-biomarker panel obtains leave-one-out cross-validation (LOOCV) accuracy to
      0.7857 by nearest centroid classifier. An independent test of this panel by
      support vector machine (SVM) with threefold cross validation gets an AUC 0.8438.
      This greatly improves the predictive accuracy by 20% over the single best
      biomarker. Further extension of this 4-biomarker panel to a larger 13-biomarker
      panel improves the LOOCV to 0.8673 with independent AUC 0.8437. Comparison with
      the exhaustive search method shows that our method dramatically reduces the
      searching time by 1000-fold. Experiments on the early cancer stage samples reveal
      two panel of biomarkers and show promising accuracy. The proposed method allows
      us to select the subset of biomarkers with best accuracy to distinguish case and
      control samples given the number of selected biomarkers. Both receiver operating
      characteristic curve and precision-recall curve show our method's consistent
      performance gain in accuracy. Our method also shows its advantage in capturing
      synergy among selected biomarkers. The multi-biomarker panel far outperforms the
      simple combination of best single features. Close investigation of the multi
      biomarker panel illustrates that our method possesses the ability to remove
      redundancy and reveals complementary biomarker combinations. In addition, our
      method is efficient and can select multi-biomarker panel with more than 5
      biomarkers, for which the exhaustive methods fail. In conclusion, we propose a
      promising model to improve the clinical data interpretability and to serve as a
      useful tool for other complex disease studies. Our small multi-biomarker panel,
      CEA, IL-10, IMA, and NSE, may provide insights on the disease status of
      colorectal diseases. The implementation of our method in MATLAB is available via
      the website: http://doc.aporc.org/wiki/MILP_k. 

PMID- 25980369
TI  - Nanometric molecular separation measurements by single molecule photobleaching.
AB  - Although considerable progress has been made in imaging distances in cells below
      the diffraction limit using FRET and super-resolution microscopy, methods for
      determining the separation of macromolecules in the 10-50 nm range have been
      elusive. We have developed fluorophore localisation imaging with photobleaching
      (FLImP), based on the quantised bleaching of individual protein-bound dye
      molecules, to quantitate the molecular separations in oligomers and nanoscale
      clusters. We demonstrate the benefits of using our method in studying the
      nanometric organisation of the epidermal growth factor receptor in cells.

PMID- 25980370
TI  - In vitro growth, cytopathic effects and clearance of monolayers by clinical
      isolates of Balamuthia mandrillaris in human skin cell cultures.
AB  - Balamuthia mandrillaris is a free-living ameba (FLA) that has been isolated or
      its DNA identified in soil, dust and water. It causes a fatal central nervous
      system infection in humans and animals. Although it is environmental as
      Acanthamoeba and Naegleria fowleri, the two other free-living amebae that also
      cause CNS infections in humans and other animals, Balamuthia does not feed on
      bacteria as the other FLA. In the laboratory, it can be grown on a variety of
      mammalian cell cultures. In this study we examined the ability of three different
      Balamuthia isolates to grow on several different human skin cell cultures
      including the WT/A keratinocyte cell cultures. A corneal isolate of Acanthamoeba
      castellanii was used for comparison. 

PMID- 25980371
TI  - Quantifying above- and belowground biomass carbon loss with forest conversion in
      tropical lowlands of Sumatra (Indonesia).
AB  - Natural forests in South-East Asia have been extensively converted into other
      land-use systems in the past decades and still show high deforestation rates.
      Historically, lowland forests have been converted into rubber forests, but more
      recently, the dominant conversion is into oil palm plantations. While it is
      expected that the large-scale conversion has strong effects on the carbon cycle,
      detailed studies quantifying carbon pools and total net primary production
      (NPPtotal ) in above- and belowground tree biomass in land-use systems replacing
      rainforest (incl. oil palm plantations) are rare so far. We measured above- and
      belowground carbon pools in tree biomass together with NPPtotal in natural old
      growth forests, 'jungle rubber' agroforests under natural tree cover, and rubber
      and oil palm monocultures in Sumatra. In total, 32 stands (eight plot replicates
      per land-use system) were studied in two different regions. Total tree biomass in
      the natural forest (mean: 384 Mg ha(-1) ) was more than two times higher than in
      jungle rubber stands (147 Mg ha(-1) ) and >four times higher than in monoculture
      rubber and oil palm plantations (78 and 50 Mg ha(-1) ). NPPtotal was higher in
      the natural forest (24 Mg ha(-1)  yr(-1) ) than in the rubber systems (20 and 15
      Mg ha(-1)  yr(-1) ), but was highest in the oil palm system (33 Mg ha(-1)  yr(-1)
      ) due to very high fruit production (15-20 Mg ha(-1)  yr(-1) ). NPPtotal was
      dominated in all systems by aboveground production, but belowground productivity
      was significantly higher in the natural forest and jungle rubber than in
      plantations. We conclude that conversion of natural lowland forest into different
      agricultural systems leads to a strong reduction not only in the biomass carbon
      pool (up to 166 Mg C ha(-1) ) but also in carbon sequestration as carbon
      residence time (i.e. biomass-C:NPP-C) was 3-10 times higher in the natural forest
      than in rubber and oil palm plantations. 

PMID- 25980372
TI  - Pediatric Extracorporeal Membrane Oxygenation: An Introduction for Emergency
      Medicine Physicians.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) therapy has supported
      critically ill pediatric patients in the intensive care unit setting with cardiac
      and respiratory failure. This therapy is beginning to transition to the emergency
      department setting. OBJECTIVE OF REVIEW: This article describes the fundamentals
      of ECMO and familiarizes the emergency medicine physician with its use in
      critically ill pediatric patients. DISCUSSION: ECMO can be utilized as either
      venoarterial (VA) or venovenous (VV), to support oxygenation and perfusion in
      respiratory failure, sepsis, cardiac arrest, and environmental hypothermia.

PMID- 25980373
TI  - A new approach for cerumenolytic treatment in children: In vivo and in vitro
      study.
AB  - OBJECTIVES: To demonstrate the effects of various cerumenolytic solutions in vivo
      and in vitro and to measure the change in pain following treatment. METHODS: The
      study was done as a single-centre, prospective and double-blind study. Among 1243
      paediatric patients with total or nearly total occlusive plug in 4 years period,
      those who accepted endoscopic ear examination and cleaning via aspiration after a
      follow-up period of at least 10 days following treatment were included in the
      study. Day of total TM visualisation was noted and removal co-efficient was
      calculated. The pre and post-treatment pain levels of the patients were assessed
      using analogue chromatic continuous scale (ACCS). In the in vitro part, cerumen
      samples collected at equal amounts from 20 patients were treated at 36-400
      degrees C in 6 different tubes with the same solutions and their dissolution
      degrees were assessed over a period of 5 days (Hour 6, Hour 12, Hour 48, Hour 72,
      Hour 92, Hour 120). Additionally, the degree of resolution in the tube treated
      with distilled water was considered to be the control reference. RESULTS: In the
      in vivo part of the study, total TM visualisation was observed in Group 1 at
      50.2% (Day 3), in Group at 57.1%, in Group at 62.3%, in Group at 44.3% and in
      Group 5 at 73.5%. The group with the lowest removal co-efficient was Group 5
      (removal co-efficient=1.623). In reference to the ACCS pain scores of the
      patients, the intra-group change pre-post treatment was found statistically
      significant for all groups (p=0.008; p=0.0222; p=0.005; p=0.026; p=0.018). After
      statistical analysis between the groups the difference between Group 5 and other
      groups was found statistically significant (p=0.002; p=0.026; p=0.044; p=0.034).
      In the in vitro part of the study, the best dissolution was observed in Group 2.
      CONCLUSIONS: In our study, the best cerumenolytic solutions were identified to be
      glycerine 10cc+3% hydrogen peroxide 10cc+10% sodium bicarbonate 10cc+distilled
      water 10cc. Especially the use of this mixture ease in terms of pain for the
      patient and in terms of time and comfort for the physician during the removal
      procedure.

PMID- 25980374
TI  - Bridging bronchus: Importance of recognition on airway endoscopy.
AB  - Bridging bronchus is an anomalous bronchus, which crosses the mediastinum from
      the contralateral mainstem bronchus and it is commonly associated with congenital
      great vessel abnormalities. This is a case report of an infant that underwent
      airway endoscopy and attempt at cannulation of a mainstem bronchus with supposed
      bronchial cast after cardiac surgery in the intensive care unit. After multiple
      failed attempts, further workup was completed which revealed a bridging bronchus.
      A bridging bronchus must be suspected in a patient with abnormal appearing
      endoscopy in presence of great vessel anomalies to prevent accidental injury to
      the tracheobronchial tree. 

PMID- 25980375
TI  - The goldfish conditioned withdrawal preparation: effects of some basic
      methodological variables.
AB  - Barela (Psychological Reports, 110: 173-186, 2012) presented a novel preparation
      for the experimental study of classical fear conditioning in goldfish, and
      successfully employed it in the demonstration of several basic conditioning
      principles. The present research addressed some basic methodological questions
      using a modified version of this preparation. Results indicated that the
      modification made to the visual CS increased its efficacy, and that conditioning
      to this stimulus was directly related to the number of CS-US trials given, US
      intensity, and intertrial interval. In addition, conditioning was detected with
      interstimulus intervals both shorter and longer than those used previously, as
      well as with an auditory CS. Methodological implications for the future
      employment of this preparation are discussed. 

PMID- 25980376
TI  - Bottom-up approaches to strengthening child protection systems: Placing children,
      families, and communities at the center.
AB  - Efforts to strengthen national child protection systems have frequently taken a
      top-down approach of imposing formal, government-managed services. Such expert
      driven approaches are often characterized by low use of formal services and the
      misalignment of the nonformal and formal aspects of the child protection system.
      This article examines an alternative approach of community-driven, bottom-up work
      that enables nonformal-formal collaboration and alignment, greater use of formal
      services, internally driven social change, and high levels of community
      ownership. The dominant approach of reliance on expert-driven Child Welfare
      Committees produces low levels of community ownership. Using an approach
      developed and tested in rural Sierra Leone, community-driven action, including
      collaboration and linkages with the formal system, promoted the use of formal
      services and achieved increased ownership, effectiveness, and sustainability of
      the system. The field needs less reliance on expert-driven approaches and much
      wider use of slower, community-driven, bottom-up approaches to child protection. 

PMID- 25980377
TI  - High neutrophil to lymphocyte ratio in type A acute aortic dissection facilitates
      diagnosis and predicts worse outcome.
AB  - OBJECTIVE: The authors investigated whether neutrophil to lymphocyte ratio (N/L)
      can contribute to the diagnosis and risk assessment in patients with type A acute
      aortic dissection (AAD). METHODS: The authors studied 120 consecutive patients
      with type A AAD (group I) and compared them with 121 consecutive patients with
      chronic aneurysms (group II) and 121 age- and sex-matched healthy subjects (group
      III). RESULT: It was found that white blood cell count, N/L, D-dimer and C
      reactive protein were significantly higher in group I versus both groups II and
      III (p < 0.001 for all comparisons). White blood cell count and D-dimer were much
      higher in patients who died compared to survivors in group I (p = 0.023 and p =
      0.033, respectively). A cutoff value of N/L >4.6 was associated with 0.89
      sensitivity and 0.91 specificity for AAD. CONCLUSION: High N/L may contribute to
      the diagnostic evaluation and prompt immediate therapy in patients with type A
      AAD.

PMID- 25980378
TI  - Towards a Validation of the Three Pathways Model of Pathological Gambling.
AB  - With the aim of validating the three pathways hypothesis of pathological gambling
      (Blaszczynski and Nower in Addiction 97:487-499, 2002) 372 pathological gamblers
      meeting DSM IV (2000) criteria were assessed via a structured clinical interview
      as well as being subjected to personality tests and evaluation of their gambling
      practices. Our results show that it is possible to identify three subgroups
      corresponding to the three pathways: behaviourally conditioned problem gamblers,
      emotionally vulnerable problem gamblers and antisocial impulsivist problem
      gamblers. Our results particularly demonstrate that impulsivist gamblers
      preferentially choose semi-skilful gambling (horse racing and sports gambling)
      whereas emotionally vulnerable gamblers are significantly more attracted to games
      of chance (one-armed bandits, scratch cards, etc.) This led us to propose a
      functional presentation of the three pathways model which differs somewhat from
      the Blaszczynski and Nower presentation. 

PMID- 25980379
TI  - EFFECTS OF FIVE DIVERSE LIGNOCELLULOSIC DIETS ON DIGESTIVE ENZYME BIOCHEMISTRY IN
      THE TERMITE Reticulitermes flavipes.
AB  - Termites have recently drawn much attention as models for biomass processing,
      mainly due to their lignocellulose digestion capabilities and mutualisms with
      cellulolytic gut symbionts. This research used the lower termite Reticulitermes
      flavipes to investigate gut enzyme activity changes in response to feeding on
      five diverse lignocellulosic diets (cellulose filter paper [FP], pine wood [PW],
      beech wood xylan [X], corn stover [CS], and soybean residue [SB]). Our objectives
      were to compare whole-gut digestive enzyme activity and host versus symbiont
      contributions to enzyme activity after feeding on these diets. Our hypothesis was
      that enzyme activities would vary among diets as an adaptive mechanism enabling
      termites and symbiota to optimally utilize variable resources. Results support
      our "diet-adaptation" hypothesis and further indicate that, in most cases, host
      contributions are greater than those of symbionts with respect to the enzymes and
      activities studied. The results obtained thus provide indications as to which
      types of transcriptomic resources, termite or symbiont, are most relevant for
      developing recombinant enzyme cocktails tailored to specific feedstocks. With
      regard to the agricultural feedstocks tested (CS and SB), our results suggest
      endoglucanase and exoglucanase (cellobiohydrolase) activities are most relevant
      for CS breakdown; whereas endoglucanase and xylosidase activities are relevant
      for SB breakdown. However, other unexplored activities than those tested may also
      be important for breakdown of these two feedstocks. These findings provide new
      protein-level insights into diet adaptation by termites, and also complement host
      symbiont metatranscriptomic studies that have been completed for R. flavipes
      after FP, PW, CS, and SB feeding. 

PMID- 25980381
TI  - Predictive factors for preterm delivery under rural conditions in post-tsunami
      Banda Aceh.
AB  - OBJECTIVE: To assess the risk for preterm deliveries <37 week of gestation and
      associated prevalence of vaginal infection in a rural setting after the tsunami
      in Banda Aceh, Indonesia. METHODS: Wet mount microscopy, vaginal pH and vaginal
      swabs for microbiological culture were collected in pregnant women during the 2nd
      trimester from February to June of 2005 in four temporary outpatient clinics and
      the patients were followed up until delivery. RESULTS: One hundred and fifty-nine
      pregnant patients were screened. Sixty-two could be followed up until delivery.
      Thirty-nine (62.9%) delivered at term and 23 (37.1%) delivered prematurely.
      Significant risk factors for preterm delivery were a history of preterm delivery
      and group B streptococcus infection. Increased vaginal pH alone had no
      significant influence on preterm delivery, although there was a trend.
      CONCLUSION: The rate of preterm delivery was high in this cohort. We suggest risk
      stratification for preterm delivery in rural conditions by performing a vaginal
      pH and wet mount microscopy. If either is suspect we suggest collecting a vaginal
      swab for microbiological culture for targeted treatment. Patients with a history
      of preterm delivery are at increased risk and should be monitored closely.

PMID- 25980380
TI  - Waist-to-height ratio is more closely associated with alanine aminotransferase
      levels than body mass index and waist circumference among population-based
      children: a cross-sectional study in Japan.
AB  - BACKGROUND: An association between anthropometric measurements, including waist
      circumference (WC), and alanine aminotransferase (ALT) levels has been reported
      among adults. However, studies conducted among population-based elementary
      schoolchildren to date have been limited, especially in Japan, where the
      measurement of WC and blood collection are not usually performed in the annual
      health examination at elementary schools. The present study investigated the
      association between anthropometric measurements and ALT levels among population
      based elementary schoolchildren in Japan. METHODS: Subjects were fourth-grade
      schoolchildren (aged 9 or 10) from the town of Ina in Saitama Prefecture, Japan
      during 2004-2009. The height, weight, and WC of each subject were measured, and
      blood samples were drawn to measure ALT levels. Childhood overweight or obesity
      was defined according to the age- and sex-specific cut-off points proposed by the
      International Obesity Task Force. Spearman's correlation coefficients between
      anthropometric measurements (body mass index (BMI), WC, and waist-to-height ratio
      (WHtR)) and ALT levels were calculated. RESULTS: Data from 2499 subjects (1293
      boys and 1206 girls) were analyzed. BMI, WC, and WHtR were significantly
      positively correlated with ALT levels; the correlation coefficient of ALT levels
      with WHtR was higher than that with BMI and WC in boys and girls. In the analysis
      stratified by physique (non-overweight/obesity, overweight, or obesity), all
      anthropometric measurements were significantly positively correlated with ALT
      levels among boys, while only WHtR was significantly positively correlated with
      ALT levels among girls. Moreover, the correlation coefficient of ALT levels with
      WHtR was more pronounced than that with BMI and WC in the non-overweight/obesity
      group, in the overweight group, and in the obesity group for each sex.
      CONCLUSIONS: The present study showed that WHtR was more closely associated with
      ALT levels than BMI and WC. Furthermore, only WHtR was significantly positively
      associated with ALT levels regardless of sex and physique. This study suggests
      that it is more useful to monitor WHtR than BMI and WC as a surrogate for ALT
      levels among population-based elementary schoolchildren.

PMID- 25980382
TI  - Biogenesis of mitochondrial outer membrane proteins, problems and diseases.
AB  - Proteins of the mitochondrial outer membrane are synthesized as precursors on
      cytosolic ribosomes and sorted via internal targeting sequences to mitochondria.
      Two different types of integral outer membrane proteins exist: proteins with a
      transmembrane beta-barrel and proteins embedded by a single or multiple alpha
      helices. The import pathways of these two types of membrane proteins differ
      fundamentally. Precursors of beta-barrel proteins are first imported across the
      outer membrane via the translocase of the outer membrane (TOM complex). The TOM
      complex is coupled to the sorting and assembly machinery (SAM complex), which
      catalyzes folding and membrane insertion of these precursors. The mitochondrial
      import machinery (MIM complex) promotes import of proteins with multiple alpha
      helical membrane spans. Depending on the topology precursors of proteins with a
      single alpha-helical membrane anchor are imported via several distinct routes. We
      summarize current models and open questions of biogenesis of mitochondrial outer
      membrane proteins and discuss the impact of malfunctions of protein sorting on
      the development of diseases. 

PMID- 25980383
TI  - A cyclization-induced emission enhancement (CIEE)-based ratiometric fluorogenic
      and chromogenic probe for the facile detection of a nerve agent simulant DCP.
AB  - The first ratiometric fluorescent probe for the detection of a nerve agent
      simulant was developed based on tandem phosphorylation and intramolecular
      cyclization, by which high sensitivity as well as large emission shift could be
      achieved. 

PMID- 25980384
TI  - Nano-CeO2 decorated graphene based chitosan nanocomposites as enzymatic
      biosensing platform: fabrication and cellular biocompatibility assessment.
AB  - The present study summarizes the designing of a green transducer phase based on
      nano-cerium oxide (CeO2) decorated reduced graphene oxide (RGO) reinforced
      chitosan nanocomposites as an effective enzyme immobilizer and bio-sensing matrix
      for glucose analyte. Also, it scrutinizes the biocompatibility and cell viability
      of the synthesized nanohybrid with human fibroblastic macrophage cell line. CeO2
      nanoparticles (NPs) were successfully grown on graphene nanosheet in the presence
      of cationic surfactant followed by facile hydrothermal treatment. The eventual
      growth of synthesized CeO2 nanocrystals on the graphene layer was confirmed from
      X-ray diffraction (XRD), transmission electron microscopy (TEM) and Raman
      analysis. The biocompatibility of the synthesized nanohybrid was also evident
      from the MTT assay. Glucose oxidase (GOx) was employed on the green polymer
      nanocomposites modified FTO electrode to fabricate an enzymatic bioelectrode. The
      electroanalytical response of the GOx/nano-CeO2/RGO/CS/FTO bioelectrode towards
      electrooxidation of glucose analyte was investigated by electrochemical impedance
      (EIS) and cyclic voltammetry (CV) study. The resulting biosensor exhibited a good
      electrochemical response to glucose within the linear detection range of 0.05-6.5
      mM with a low detection limit of 2 MUM and a sensitivity of 7.198 MUA mM(-1) cm(
      2). The bioelectrode also showed good shelf life (~10 weeks) and negligible
      interfering ability under controlled environment. The obtained results indicate
      that nano-CeO2/RGO nanohybrid based chitosan nanocomposites achieve a
      biocompatible biosensing platform for effective enzyme immobilization due to the
      excellent synergistic effects between the CeO2 nanoparticles and graphene sheet. 

PMID- 25980385
TI  - Factors affecting the evacuation rate of intracerebral hemorrhage in basal
      ganglia treated by minimally invasive craniopuncture.
AB  - OBJECTIVE: Minimally invasive craniopuncture has been used to treat intracerebral
      hemorrhage (ICH) for over 20 years in China. However, one-off total evacuation of
      hematoma cannot be achieved through this procedure because it is not an open
      surgery. This study is designed to identify factors that can increase the
      hematoma evacuation rate (ER) of this procedure and to evaluate the influence of
      ER on long-term outcome. METHODS: A total of 309 patients with basal ganglia ICH
      treated by minimally invasive craniopuncture were analyzed retrospectively.
      Univariate and multivariate linear regression analyses were used to identify
      factors correlated with a high ER. The correlation between ER and long-term
      outcome was also analyzed by logistic regression and the Spearman correlation.
      RESULTS: A low hematoma mean CT number (beta=-0.773, p<0.001) and postoperative
      cerebrospinal fluid (CSF) outflow (beta=0.193, p<0.001) were found to be
      independent factors associated with a high ER. In patients with 30-50ml of
      hematoma, a high ER was correlated with a high Barthel index improvement
      (r=0.611, p<0.001) and a high modified Rankin scale decline (r=0.517, p<0.001).
      In patients with 50-80ml of hematoma, a high ER was a protective factor of case
      fatality (B=-2.297, p=0.005). CONCLUSIONS: The hematoma mean CT number can
      predict the efficiency of minimally invasive craniopuncture in patients with ICH.
      In patients with ventricular involvement, the tip of the puncture needle should
      be placed close to the tear in the ventricle rather than at the center of the
      hematoma to facilitate postoperative CSF outflow.

PMID- 25980386
TI  - Eye contact reveals a relationship between Neuroticism and anterior EEG
      asymmetry.
AB  - Although anterior functional brain asymmetry has been linked to individual
      differences in affect and motivation, its relations with the Five Factor Model
      personality traits remain unclear. We investigated anterior EEG alpha-activity
      asymmetry in response to variable degrees of social contact induced by different
      gaze directions of a "live" model. Neuroticism was negatively related to the
      anterior EEG asymmetry scores in response to direct gaze, indicating that higher
      levels of Neuroticism were associated with avoidance-related, relative right
      sided functional brain asymmetry. Neuroticism was also related to behavioral
      direct gaze avoidance and subjective averted gaze preference. These relationships
      arose primarily from the Withdrawal aspect factor, suggesting that two subdomains
      of Neuroticism may be differentially related to approach-avoidance tendencies.
      These findings demonstrate that experimental manipulations of social contact can
      reveal personality related differences in anterior EEG asymmetry responsiveness,
      offering a motivationally salient alternative to resting state measures. 

PMID- 25980387
TI  - Phase microscopy using light-field reconstruction method for cell observation.
AB  - The refractive index (RI) distribution can serve as a natural label for undyed
      cell imaging. However, the majority of images obtained through quantitative phase
      microscopy is integrated along the illumination angle and cannot reflect
      additional information about the refractive map on a certain plane. Herein, a
      light-field reconstruction method to image the RI map within a depth of 0.2 MUm
      is proposed. It records quantitative phase-delay images using a four-step phase
      shifting method in different directions and then reconstructs a similar scattered
      light field for the refractive sample on the focus plane. It can image the RI of
      samples, transparent cell samples in particular, in a manner similar to the
      observation of scattering characteristics. The light-field reconstruction method
      is therefore a powerful tool for use in cytobiology studies.

PMID- 25980389
TI  - Shape analysis based on depth-ordering.
AB  - In this paper we propose a new method for shape analysis based on the ordering of
      shapes using band-depth. We use this band-depth to non-parametrically define a
      global depth for a shape with respect to a reference population, typically
      consisting of normal control subjects. This allows us to globally quantify
      differences with respect to "normality". Using the depth-ordering of shapes also
      allows the detection of localized shape differences by using alpha-central values
      of shapes. We propose permutation tests to statistically assess global and local
      shape differences. We further determine the directionality of shape differences
      (local inflation versus deflation). The method is evaluated on a synthetically
      generated striatum dataset, and applied to detect shape differences in the
      hippocampus between subjects with first-episode schizophrenia and normal
      controls. 

PMID- 25980388
TI  - Construction of 4D high-definition cortical surface atlases of infants: Methods
      and applications.
AB  - In neuroimaging, cortical surface atlases play a fundamental role for spatial
      normalization, analysis, visualization, and comparison of results across
      individuals and different studies. However, existing cortical surface atlases
      created for adults are not suitable for infant brains during the first two
      postnatal years, which is the most dynamic period of postnatal structural and
      functional development of the highly-folded cerebral cortex. Therefore,
      spatiotemporal cortical surface atlases for infant brains are highly desired yet
      still lacking for accurate mapping of early dynamic brain development. To bridge
      this significant gap, leveraging our infant-dedicated computational pipeline for
      cortical surface-based analysis and the unique longitudinal infant MRI dataset
      acquired in our research center, in this paper, we construct the first
      spatiotemporal (4D) high-definition cortical surface atlases for the dynamic
      developing infant cortical structures at seven time points, including 1, 3, 6, 9,
      12, 18, and 24 months of age, based on 202 serial MRI scans from 35 healthy
      infants. For this purpose, we develop a novel method to ensure the longitudinal
      consistency and unbiasedness to any specific subject and age in our 4D infant
      cortical surface atlases. Specifically, we first compute the within-subject mean
      cortical folding by unbiased groupwise registration of longitudinal cortical
      surfaces of each infant. Then we establish longitudinally-consistent and unbiased
      inter-subject cortical correspondences by groupwise registration of the geometric
      features of within-subject mean cortical folding across all infants. Our 4D
      surface atlases capture both longitudinally-consistent dynamic mean shape changes
      and the individual variability of cortical folding during early brain
      development. Experimental results on two independent infant MRI datasets show
      that using our 4D infant cortical surface atlases as templates leads to
      significantly improved accuracy for spatial normalization of cortical surfaces
      across infant individuals, in comparison to the infant surface atlases
      constructed without longitudinal consistency and also the FreeSurfer adult
      surface atlas. Moreover, based on our 4D infant surface atlases, for the first
      time, we reveal the spatially-detailed, region-specific correlation patterns of
      the dynamic cortical developmental trajectories between different cortical
      regions during early brain development. 

PMID- 25980390
TI  - Acute kidney injury in hepatitis B-related acute-on-chronic liver failure without
      preexisting liver cirrhosis.
AB  - BACKGROUND AND AIM: Acute kidney injury (AKI), as defined by the Acute Kidney
      Injury Network, has been widely investigated in decompensated liver cirrhosis
      patients. AKI is frequently progressive and independently associated with
      mortality in these patients. However, in the Asia-Pacific region, the majority of
      cases of acute-on-chronic liver failure (ACLF) are caused by acute exacerbation
      of chronic hepatitis B without preexisting cirrhosis. It is not clear whether
      these patients are at similar risk as those with underlying cirrhosis. METHODS:
      We performed a retrospective cohort analysis of hepatitis B-related ACLF patients
      in a single center from January 2004 through December 2011 and evaluated the
      occurrence of AKI after admission and its relation to the 3-month mortality of
      ACLF patients. RESULTS: A total of 439 patients with hepatitis B-related ACLF
      without preexisting cirrhosis were enrolled, and 158 patients (36.0%) developed
      AKI during hospitalization. ACLF patients with AKI had higher serum creatinine,
      bilirubin, and INR values and MELD scores as well as more complications compared
      to those without AKI (p < 0.01). The occurrence of AKI and its stage affect the 3
      month mortality of ACLF patients (p < 0.001), and a greater percentage of AKI was
      found in non-survivors than survivors (56.7 vs. 27.6%, p < 0.001). The cumulative
      survival of patient with no AKI, AKI stage 1, 2 and 3 was 77.84, 65.46, 41.38 and
      27.03%, respectively. CONCLUSIONS: In our study, we observed that AKI was
      associated with increased 3-month mortality in hepatitis B-related ACLF patients
      without preexisting cirrhosis. Higher AKI stage predicted a worse prognosis. Our
      findings support the importance of early identification and timely therapy of AKI
      in hepatitis B-related ACLF patients.

PMID- 25980391
TI  - Research highlights: natural passive samplers--plants as biomonitors.
AB  - In the past decade, interest in boosting the collection of data on environmental
      pollutants while reducing costs has spurred intensive research into passive
      samplers, instruments that monitor the environment through the free flow of
      chemical species. These devices, although relatively inexpensive compared to
      active sampling technologies, are often tailored for collection of specific
      contaminants or monitoring of a single phase, typically water or air. Plants as
      versatile, natural passive samplers have gained increased attention in recent
      years due to their ability to absorb a diverse range of chemicals from the air,
      water, and soil. Trees, lichens, and other flora have evolved exquisite
      biological features to facilitate uptake of nutrients and water from the ground
      and conduct gas exchange on an extraordinary scale, making them excellent
      monitors of their surroundings. Sampling established plant specimens in a region
      also provides both historical and spatial data on environmental contaminants at
      relatively low cost in a non-invasive manner. This Highlight presents several
      recent publications that demonstrate how plant biomonitoring can be used to map
      the distribution of a variety of pollutants and identify their sources. 

PMID- 25980393
TI  - Copper(I)-Catalyzed Cycloaddition of Azides to Multiple Alkynes: A Selectivity
      Study Using a Calixarene Framework.
AB  - Copper(I)-catalyzed addition of limited amounts of azides to multiple alkynes,
      which led to statistical mixtures of triazole/acetylene derivatives or, in other
      cases, resulted in preferred formation of multiple triazoles, was studied at pre
      organizable calixarene platforms bearing up to four propargyl groups. Depending
      on calixarene structures and reaction conditions, the unprecedented specific or
      selective formation of exhaustively triazolated calixarenes or a complete loss of
      the selectivity were observed. Both autocatalytic copper activation and a local
      copper(I) concentration increase due to copper-triazole complexation were
      thoroughly studied as the most expected reasons for the selectivity and both were
      disproved. Mixed triazolated/propargylated calixarenes and their copper(I)
      complexes proved not to be involved in the cascade-like process that was modeled
      to be driven by an intramolecular transfer of two copper(I) ions from a just
      formed binuclear copper intermediate to the adjacent acetylene unit. 

PMID- 25980394
TI  - Dramatically reduced incidence of vaginal cuff dehiscence in gynecologic patients
      undergoing endoscopic closure with barbed sutures: A retrospective cohort study.
AB  - INTRODUCTION: This retrospective study documented the rate of vaginal cuff
      dehiscence (VCD) in a large series of gynecologic patients who were treated with
      an endoscopic (robotic-assisted or laparoscopic) hysterectomy that incorporated
      either delayed absorbable monofilament barbed or vicryl running sutures. METHOD:
      We sought to discern any prognostic associations between operative variables
      (e.g., closure type (barbed or vicryl sutures), endoscopic approach (robotic
      assisted or laparoscopic), and energy source (Harmonic Ace Shears or
      monopolar/bipolar electro-surgery)) and the risk for VCD via patient chart
      review. Statistical evaluation was comprised of univariate analyses and multiple
      regression. RESULTS: We identified 1876 subjects; there were 14 cases (0% with
      barbed suture and 0.99% with vicryl suture) of VCD (an overall incidence of
      0.75%), nearly all of which were associated with a robotic-assisted hysterectomy
      involving vicryl sutures (p = 0.034). However, the type of endoscopic surgery (P
      = 0.11) and energy source (P = 0.28) were not significant prognostic factors. The
      VCD patients' exhibited a median duration of 47 days (range, 14-116) until the
      development of their condition. CONCLUSION: Vaginal cuff separation subsequent to
      laparoscopic closure is a rare occurrence. While our incidence of VCD was low and
      comparable to other reported rates in the literature, we did not observe any
      cases of VCD following laparoscopic hysterectomy performed with barbed suture
      closure.

PMID- 25980395
TI  - Intra abdominal hypertension; incidence, prevalence and outcomes in a mixed
      intensive care unit: Prospective cohort study.
AB  - BACKGROUND: This study was conducted primarily to determine the prevalence and
      incidence of intra-abdominal hypertension (IAH) in a mixed ICU (medical &
      surgical) population and, secondarily, to compare outcomes between patients with
      and without IAH. METHODS: The prospective cohort study was conducted from April
      to July 2011 on adult patients admitted in ICU, on mechanical ventilation and
      with an indwelling urinary catheter. Intra-vesicular pressure was measured.
      Primary endpoint was IAH and it was defined as Intra-abdominal pressure>12 mm Hg
      on two consecutive readings 6 h apart. RESULTS: Total 83 patients were enrolled
      in the study; 61% from medical services and 39% from surgical services. Mean age
      in years+/-SD was 47 +/- 17.5 with male preponderance (66%). IAH was detected in
      23/83 (28%) at the time of admission, while six out of remaining 60 patients
      (10%) developed the condition during their ICU stay; the incidence and prevalence
      was 10% and 35%, respectively. Secondary end points of the study comparing
      outcomes between patients with and without IAH, though different in the two
      groups, did not achieve statistical significance. In-hospital mortality 65.5% vs.
      44.4% p-value 0.054. New onset renal failure 34.5% vs. 16.7% p-value 0.054%.
      Difficulty in weaning from mechanical ventilation 37.9% vs. 25.9% p-value 0.008.
      CONCLUSION: IAH is a poorly recognized clinical entity with potentially
      devastating impact on patient outcomes. Since majority of patients had IAH at the
      time of admission, all ICU patients especially on ventilator should have baseline
      intra-abdominal pressures measured at the time of admission and subjected to
      appropriate management to prevent them from developing abdominal compartment
      syndrome.

PMID- 25980396
TI  - Constipation is not associated with diverticular disease - Analysis of 976
      patients.
AB  - BACKGROUND: In the light of controversial data in the literature, the present
      study was designed to evaluate potential associations between colonic
      diverticular disease, constipation and quality of life. DESIGN: We prospectively
      enrolled 976 consecutive patients, who participated in the nationwide colorectal
      cancer screening program in four medical centers between 2008 and 2009. All
      patients underwent full colonoscopy and completed a standardized questionnaire.
      The severity of constipation was assessed by the validated Wexner constipation
      score. Quality of Life (QOL) was evaluated by the SF-12 health score. RESULTS:
      The median age was 62 years (range 22-90) and the male to female ratio was 1:1.
      Colonic diverticular disease was found in 290 participants (30%). Age, body mass
      index and diabetes mellitus were significantly associated with the presence of
      diverticular disease (p < 0.0001, p = 0.0007 and p = 0.0178). The median
      constipation score in patients with diverticular disease was 3 (range 0-18), and
      comparable to patients without diverticula (p = 0.1073). The physical component
      summary of the SF-12 was significantly reduced in patients with diverticular
      disease (p = 0.0038). CONCLUSION: This large population based study revealed no
      association between colonic diverticular disease and constipation. Notably, the
      presence of diverticular disease significantly impacts quality of life.

PMID- 25980397
TI  - Effect of sustentaculum screw placement on outcomes of intra-articular calcaneal
      fracture osteosynthesis: A prospective cohort study using 3D CT.
AB  - INTRODUCTION: Correct placement of the sustentacular screw is an important
      component during the open reduction and internal fixation of calcaneal fractures.
      The hypothesis of this study is that certain 3D-CT images would help detect the
      real placement of the sustentaculum screw. The aims of the study are to
      investigate the postoperative status of the sustentacular screw and to evaluate
      the effect of the sustentaculum screw placement on the treatment of intra
      articular calcaneal fractures. PATIENTS AND METHODS: 119 patients with intra
      articular calcaneal fractures meeting the inclusion criteria were included in
      this prospective study. The postoperative sustentaculum screw was detected via
      radiographs and CT scans. According to the placement of the screw, the patients
      were divided into three groups: the sustentaculum screw with accurate fixation
      (group A), marginal fixation (group B), and non-fixation (group C). The
      perioperative parameters and the change of Bohler's angles on the postoperative
      and final follow-up radiographs were analyzed. The clinical outcomes were
      evaluated by the AOFAS ankle-hindfoot score and Short Form-36 questionnaire.
      RESULTS: Eighty-five patients were followed up with an average time of 26 (range,
      12-48) months. 3D-CT confirmed that 18 cases were in group A, 33 in group B, and
      34 in group C. Except the length of stay, significant difference in the operating
      time and blood loss existed among three groups (P < 0.05). The mean decrease in
      Bohler's angle of group C was the greatest (P < 0.05). No significant difference
      could be detected in the AOFAS or SF-36 scores among the three groups either at
      the one-year follow-up or the final follow-up (P > 0.05). CONCLUSION: The
      sustentaculum screw with non-fixation may cause the decrease of Bohler's angle
      throughout the follow-up. The clinical outcomes were similar whether the screw
      was accurately placed within the sustentaculum or not.

PMID- 25980398
TI  - Cholestatic liver injury secondary to artemisinin.

PMID- 25980399
TI  - Comorbidities in Patients With Anterior Cruciate Ligament Reconstruction Compared
      With Matched Controls Without Anterior Cruciate Ligament Injury From Danish
      Registries.
AB  - PURPOSE: To describe and compare comorbidity among anterior cruciate ligament
      (ACL)-reconstructed patients and a gender- and age-matched group without ACL
      injury. Furthermore, we sought to evaluate the impact of comorbid diseases on the
      risk of ACL revision surgery. METHODS: This case-control study included 13,443
      unilateral primary ACL-reconstructed patients from the Danish Knee Ligament
      Reconstruction Register matched on gender and age with a comparison group without
      ACL injury. Information on medical comorbid conditions was obtained from the
      Danish National Registry of Patients. The prevalence of all comorbid conditions
      was described for ACL-reconstructed patients and the comparison group in terms of
      (1) the Charlson Comorbidity Index (CCI); (2) International Classification of
      Diseases, Tenth Revision disease chapters; and (3) more common chronic diseases
      in a younger population. Finally, we assessed the risk of ACL revision surgery
      according to the more common chronic diseases in a younger population, using Cox
      regression analysis. RESULTS: Although we found a large variety of diseases
      present among ACL-reconstructed patients, the percentage of patients with a CCI
      equal to 0 was high in both groups. ACL-reconstructed patients generally had a
      slightly lower prevalence of almost all International Classification of Diseases,
      Tenth Revision-classified comorbid disease groups compared with the comparison
      group without ACL injury. As expected, the prevalence of most diseases increased
      slightly with rising age. Furthermore, we found that having back pain or diseases
      of the back did alter the risk of revision surgery. CONCLUSIONS: ACL
      reconstructed patients are found to be generally healthy individuals with a low
      prevalence of serious and chronic diseases compared with an age- and gender
      matched control group from the general population. A large variety of diseases
      are present in the ACL-reconstructed group but with very low prevalence rates and
      low CCIs, indicating that the severity of their illness is limited. LEVEL OF
      EVIDENCE: Level III, case-control study.

PMID- 25980400
TI  - The Incidence of Complications of Tibial Tubercle Osteotomy: A Systematic Review.
AB  - PURPOSE: The goal of this review was to quantify the risk of perioperative and
      early postoperative complications of tibial tubercle osteotomy (TTO) with
      different techniques. METHODS: A systematic review of multiple databases was
      performed to identify studies that reported complications of TTO. Complications
      were defined as any adverse outcome, including osteotomy site nonunion, fracture,
      infection, wound complications, neurovascular complications, deep vein thrombosis
      (DVT), and pulmonary embolism (PE). Major complications were defined as nonunion,
      fracture, infections/wound complications requiring return to the operating room,
      and DVT or PE. The risk of subsequent hardware removal was also quantified.
      RESULTS: The 19 identified studies included a total of 787 TTOs: 472 direct
      medialization procedures (Elmslie-Trillat technique), 193 anteromedialization
      procedures (Fulkerson technique), and 102 procedures in which the tibial tubercle
      was completely detached for medialization or distalization, or a combination. The
      overall complication risk was 4.6%. The risk of complications was higher when the
      tibial tubercle was completely detached (10.7%) than with Elmslie-Trillat (3.3%)
      or Fulkerson (3.7%) procedures (P = .004). The overall risk of major
      complications was 3.0%. Hardware removal was performed in 36.7% of osteotomies
      and was less frequent with the Elmslie-Trillat technique (26.8%) than with the
      Fulkerson technique (49.0%) or complete tubercle detachment (48.3%) (P < .001).
      CONCLUSIONS: Tibial tubercle osteotomy is a complex surgical procedure with a
      significant risk of complications. Osteotomies that involve complete detachment
      of the tubercle have an increased risk of complications compared with those in
      which a distal cortical hinge is maintained. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level IV studies.

PMID- 25980401
TI  - Platelet-Rich Plasma Preparation Types Show Impact on Chondrogenic
      Differentiation, Migration, and Proliferation of Human Subchondral Mesenchymal
      Progenitor Cells.
AB  - PURPOSE: To evaluate the chondrogenic potential of platelet concentrates on human
      subchondral mesenchymal progenitor cells (MPCs) as assessed by histomorphometric
      analysis of proteoglycans and type II collagen. Furthermore, the migratory and
      proliferative effect of platelet concentrates were assessed. METHODS: Platelet
      rich plasma (PRP) was prepared using preparation kits (Autologous Conditioned
      Plasma [ACP] Kit [Arthrex, Naples, FL]; Regen ACR-C Kit [Regen Lab, Le Mont-Sur
      Lausanne, Switzerland]; and Dr.PRP Kit [Rmedica, Seoul, Republic of Korea]) by
      apheresis (PRP-A) and by centrifugation (PRP-C). In contrast to clinical
      application, freeze-and-thaw cycles were subsequently performed to activate
      platelets and to prevent medium coagulation by residual fibrinogen in vitro. MPCs
      were harvested from the cortico-spongious bone of femoral heads. Chondrogenic
      differentiation of MPCs was induced in high-density pellet cultures and evaluated
      by histochemical staining of typical cartilage matrix components. Migration of
      MPCs was assessed using a chemotaxis assay, and proliferation activity was
      measured by DNA content. RESULTS: MPCs cultured in the presence of 5% ACP, Regen,
      or Dr.PRP formed fibrous tissue, whereas MPCs stimulated with 5% PRP-A or PRP-C
      developed compact and dense cartilaginous tissue rich in type II collagen and
      proteoglycans. All platelet concentrates significantly (ACP, P = .00041; Regen, P
      = .00029; Dr.PRP, P = .00051; PRP-A, P < .0001; and PRP-C, P < .0001) stimulated
      migration of MPCs. All platelet concentrates but one (Dr.PRP, P = .63) showed a
      proliferative effect on MPCs, as shown by significant increases (ACP, P = .027;
      Regen, P = .0029; PRP-A, P = .00021; and PRP-C, P = .00069) in DNA content.
      CONCLUSIONS: Platelet concentrates obtained by different preparation methods
      exhibit different potentials to stimulate chondrogenic differentiation,
      migration, and proliferation of MPCs. Platelet concentrates obtained by
      commercially available preparation kits failed to induce chondrogenic
      differentiation of MPCs, whereas highly standardized PRP preparations did induce
      such differentiation. These findings suggest differing outcomes with PRP
      treatment in stem cell-based cartilage repair. CLINICAL RELEVANCE: Our findings
      may help to explain the variability of results in studies examining the use of
      PRP clinically.

PMID- 25980402
TI  - Short-Term Study of the Outcome of a New Instrument for All-Inside Double-Bundle
      Anterior Cruciate Ligament Reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the short-term clinical
      results and location of the bone tunnel with a new surgical procedure for all
      inside double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS:
      The double-bundle ACL reconstruction procedure was performed in 24 patients (13
      male and 11 female patients) with a mean age of 31.0 years. Anterior and
      posterior tibial translation using an arthrometer (KT-1000; MEDmetric, San Diego,
      CA) and the Lysholm score were measured before surgery and at a mean of 24.8
      months (range, 13 to 45 months) postoperatively. Computed tomography scans were
      taken to evaluate the bone tunnel positions using 3-dimensional images with the
      quadrant method for the femoral tunnel and Staubli's technique for the tibial
      tunnel. RESULTS: Three-dimensional computed tomography scans showed that the
      anteromedial and posterolateral tunnels were placed in anatomically appropriate
      positions. Arthrometric measurements showed that the mean side-to-side
      differences were 5.3 mm (SD, 1.6 mm) preoperatively and 0.05 mm (SD, 0.7 mm) at a
      mean of 24.8 months postoperatively, indicating a remarkable improvement (P <
      .00001). The mean Lysholm score was 56.3 points (SD, 14.8 points) preoperatively
      and 95.5 points (SD, 3.8 points) at final follow-up and was significantly
      improved after the operation (P < .00001). CONCLUSIONS: The all-inside double
      bundle ACL reconstruction technique used in this study resulted in the creation
      of tunnels in an anatomically appropriate position. Short-term clinical follow-up
      showed improvement in patient-reported outcomes and knee stability. This
      technique may provide an alternative option for all-inside ACL reconstruction.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 25980403
TI  - Best Practices During Hip Arthroscopy: Aggregate Recommendations of High-Volume
      Surgeons.
AB  - PURPOSE: To survey surgeons who perform a high volume of hip arthroscopy
      procedures regarding their operative technique, type of procedure, and
      postoperative management. METHODS: We conducted a cross-sectional survey of 27
      high-volume orthopaedic surgeons specializing in hip arthroscopy to report their
      preferences and practices related to their operative practice and postoperative
      rehabilitation protocol. All participants completed the survey in person in an
      anonymous fashion during a meeting of the American Hip Institute. RESULTS: All
      surgeons perform hip arthroscopy with the patient in the supine position,
      accessing the central compartment of the hip initially, using intraoperative
      fluoroscopy. All surgeons perform labral repair (100%), with the majority
      performing labral reconstructions (77.8%) and gluteus medius repairs (81.5%).
      There is variability in the type of anchors used during labral repair. Most
      surgeons perform capsular closure in most cases (88.9%), inject either intra
      articular cortisone or platelet-rich plasma at the conclusion of the procedure
      (59%), and prescribe a postoperative hip brace for some or all patients (59%).
      There is considerable variability in rehabilitation protocols. All surgeons
      routinely prescribe postoperative heterotopic ossification prophylaxis to their
      patients, with most surgeons (88.9%) prescribing a nonsteroidal anti-inflammatory
      medication for 3 weeks. Forty percent of the respondents use the modified Harris
      Hip Score as the most important outcome measure. CONCLUSIONS: Consistent
      practices such as use of intraoperative fluoroscopy, heterotopic ossification
      prophylaxis, and labral repair skills were identified by surveying 27 hip
      arthroscopy surgeons at high-volume centers. Most of the surgeons performed
      routine capsular closure unless underlying conditions precluded capsular release
      or plication. The survey identified higher variability between surgeons regarding
      postoperative rehabilitation protocols and use of intra-articular pharmacologic
      injections at the end of the procedure. These data may provide surgeons with a
      set of aggregate trends that may help guide training, clinical practice, and
      research in the evolving field of hip arthroscopy.

PMID- 25980404
TI  - Rapid and efficient differentiation of Yersinia species using high-resolution
      melting analysis.
AB  - The primary goal of clinical microbiology is the accurate identification of the
      causative agent of the disease. Here, we describe a method for differentiation
      between Yersinia species using PCR-HRMA. The results revealed species-specific
      melting profiles. The herein developed assay can be used as an effective method
      to differentiate Yersinia species. 

PMID- 25980406
TI  - A dynamic evolutionary and functional landscape of plant phased small interfering
      RNAs.
AB  - BACKGROUND: Secondary, phased small interfering RNAs (phasiRNAs) derived from
      protein-coding or noncoding loci (PHAS) are emerging as a new type of regulators
      of gene expression in plants. However, the evolution and function of these novel
      siRNAs in plant species remain largely unexplored. RESULTS: We systematically
      analyzed PHAS loci in 23 plant species covering major phylogenetic groups
      spanning alga, moss, gymnosperm, basal angiosperm, monocot, and dicot. We
      identified over 3,300 PHAS loci, among which ~1,600 were protein-coding genes.
      Most of these PHAS loci were novel and clade- or species-specific and showed
      distinct expression patterns in association with particular development stages,
      viral infection, or abiotic stresses. Unexpectedly, numerous PHAS loci produced
      phasiRNAs from introns or exon-intron junction regions. Our comprehensive
      analysis suggests that phasiRNAs predominantly regulate protein-coding genes from
      which they are derived and genes from the same families of the phasiRNA-deriving
      genes, in contrast to the dominant trans-regulatory mode of miRNAs. The
      stochastic occurrence of many PHAS loci in the plant kingdom suggests their young
      evolutionary origins. CONCLUSIONS: Our study discovered an unprecedented
      diversity of protein-coding genes that produce phasiRNAs in a wide variety of
      plants, and set a kingdom-wide foundation for investigating the novel roles of
      phasiRNAs in shaping phenotype diversities of plants.

PMID- 25980407
TI  - NetCooperate: a network-based tool for inferring host-microbe and microbe-microbe
      cooperation.
AB  - BACKGROUND: Host-microbe and microbe-microbe interactions are often governed by
      the complex exchange of metabolites. Such interactions play a key role in
      determining the way pathogenic and commensal species impact their host and in the
      assembly of complex microbial communities. Recently, several studies have
      demonstrated how such interactions are reflected in the organization of the
      metabolic networks of the interacting species, and introduced various graph
      theory-based methods to predict host-microbe and microbe-microbe interactions
      directly from network topology. Using these methods, such studies have revealed
      evolutionary and ecological processes that shape species interactions and
      community assembly, highlighting the potential of this reverse-ecology research
      paradigm. RESULTS: NetCooperate is a web-based tool and a software package for
      determining host-microbe and microbe-microbe cooperative potential. It
      specifically calculates two previously developed and validated metrics for
      species interaction: the Biosynthetic Support Score which quantifies the ability
      of a host species to supply the nutritional requirements of a parasitic or a
      commensal species, and the Metabolic Complementarity Index which quantifies the
      complementarity of a pair of microbial organisms' niches. NetCooperate takes as
      input a pair of metabolic networks, and returns the pairwise metrics as well as a
      list of potential syntrophic metabolic compounds. CONCLUSIONS: The Biosynthetic
      Support Score and Metabolic Complementarity Index provide insight into host
      microbe and microbe-microbe metabolic interactions. NetCooperate determines these
      interaction indices from metabolic network topology, and can be used for small-
      or large-scale analyses. NetCooperate is provided as both a web-based tool and an
      open-source Python module; both are freely available online at
      http://elbo.gs.washington.edu/software_netcooperate.html.

PMID- 25980408
TI  - Impact of smoking on perioperative outcomes after major surgery.
AB  - BACKGROUND: To investigate the impact of smoking on perioperative outcomes in
      patients undergoing one of the 16 major cardiovascular, orthopedic, or oncologic
      surgical procedures. METHODS: We relied on the American College of Surgeons
      National Surgical Quality Improvement Program database (2005 to 2011). Procedure
      specific multivariable logistic regression models assessed the association
      between smoking status (non, former, or current smokers) and risk of 30-day
      morbidity and mortality. RESULTS: Overall, 141,802 patients were identified. A
      total of 12.5%, 14.6%, and 14.9% of non, former, and current smokers,
      respectively, experienced at least one complication (P < .001). In multivariable
      models, current smokers had higher odds of overall, pulmonary, wound, and
      septic/shock complications following most cardiovascular and oncologic surgeries
      compared with nonsmokers. The odds of experiencing such adverse outcomes were
      significantly lower in former smokers compared with current smokers, but still
      higher compared with nonsmokers. CONCLUSIONS: The effect of smoking on
      perioperative outcomes is procedure dependent. Current and, even though
      mitigated, former smoking negatively influence outcomes following cardiovascular
      or oncologic procedures. Patients undergoing major procedures should be
      encouraged to discontinue tobacco smoking to achieve optimal procedural outcomes.

PMID- 25980409
TI  - Increased serum resistin levels correlate with psoriasis: a meta-analysis.
AB  - BACKGROUND: Recent studies implicate adipokines in the pathogenesis of
      inflammatory diseases, including psoriasis. In this study we evaluated the
      significance of serum resistin levels in psoriasis patients using a meta-analysis
      approach.223 METHODS: Relevant articles were retrieved by searching the following
      English and Chinese databases: Cochrane Library, PubMed, Springer Link, Chinese
      Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI).
      The retrieved studies were subjected to a thorough screening procedure to
      identify case-control studies that contained the required data. Data was
      extracted from each study and Version 12.0 STATA statistical software was
      employed for statistical analyses. RESULTS: Nine case-control studies, containing
      421 psoriasis patients and 348 healthy controls, were included in this study. The
      major result of the meta-analysis revealed a statistically significant
      association between serum resistin levels and psoriasis (SMD=2.22, 95%CI: 1.14
      3.29, P<0.001). Subgroup analysis based on ethnicity showed that, compared to the
      healthy controls, serum resistin levels were markedly higher in psoriasis
      patients in both Asian and Caucasian populations (Asians: SMD=3.27,
      95%CI=1.62~4.91, P<0.001; Caucasians: SMD=0.91, 95%CI=0.28~1.54, P<0.001).
      CONCLUSIONS: Based on our results, we conclude that serum resistin level in
      psoriasis patients is higher than healthy controls, and raises the possibility
      that elevated serum resistin levels may be a novel diagnostic marker in psoriasis
      and may predict the occurrence of co-morbidities in psoriasis patients.

PMID- 25980410
TI  - Laparoscopic plug removal for femoral nerve colic pain after mesh & plug
      hernioplasty.
AB  - BACKGROUND: Inguinal hernias account for 75% of abdominal wall hernias, with a
      lifetime risk of 27% in men and 3% in women. Major complications are recurrence,
      chronic pain, and surgical site infection, but their frequency is low. Few
      studies have reported a calcified mesh causing neuropathy by chronic compression
      of the femoral nerve after mesh & plug inguinal hernia repair. This is the first
      report of laparoscopic plug removal for femoral colic due to femoral nerve
      irritation cause by a calcified plug after mesh & plug inguinal hernia repair.
      CASE PRESENTATION: In July 2013, a 53-year-old man presented to our hospital with
      a chief complaint of colic pain in the left lower limb while walking. The patient
      had undergone left inguinal hernia repair about 10 years earlier and reported no
      chronic pain after the operation. Physical examination revealed a colic pain
      exacerbated by left thigh movement, especially during flexion, but the patient
      was pain-free at rest and had no sensory loss. Axial computed tomography and
      magnetic resonance imaging showed that the inward-projecting plug was extremely
      close to the femoral nerve. Because of the radicular symptoms and the absence of
      orthopedic and urological disease, we strongly suspected that the neuralgia was
      associated with the previous hernia operation and advised exploratory laparotomy,
      which revealed the plug bulging inward into the abdominal cavity. Moreover, the
      tip of the plug was firmly calcified and compressing the femoral nerve, which lay
      just beneath the plug, especially during hip flexion. We explanted the plug and
      his pain resolved after the operation. The patient remains pain free after 20
      months of follow up. CONCLUSION: In this study, laparoscopic hernioplasty proved
      useful for plug removal because laparoscopic instruments can easily grasp
      perilesional tissue, and laparoscopic approach has the benefit of isolating the
      plug for removal while preserving the onlay patch, and helpful for restoring
      peritoneal defects. Laparoscopic plug removal effectively resolved colic pain in
      the left thigh due to compression of the femoral nerve by a calcified plug.

PMID- 25980411
TI  - A Review: G-Quadruplex's Applications in Biological Target Detection and Drug
      Delivery.
AB  - The G-quadruplex is one of the most important DNA secondary structures and has
      elicited widespread interest in this field of scientific research. As G
      quadruplex studies have progressed, its significant roles in a variety of
      biological process have been revealed, including telomerase activity, genome
      stability, DNA replication, and oncogene expression. In addition to its
      biological functions, as a special DNA quadruplex structure, it also has
      potential for other important applications like asymmetric catalysis, probing for
      important biomarkers, acting as a vehicle for drug delivery, or as a structural
      regulator for some nanostructure designs. Here, we discuss its application to
      aspects of biological target detection and drug delivery. Its utility in
      biological target detection mainly results from its special DNAzyme activity. We
      would summarize some typical systems, utilizing G-quadruplex as signal readout
      unit, for various target detection, such as SNP, miRNAs, ions, transcription
      factors and so on. On the other hand, its use in drug delivery always relies on
      probes' structural change, as the switch of drug release. Here, we would also
      exhibit some typical drug delivery designs.

PMID- 25980412
TI  - Biological Function and Medicinal Research Significance of G-Quadruplex
      Interactive Proteins.
AB  - G-quadruplexes are four-stranded DNA structures formed from G-rich sequences that
      are built around tetrads of hydrogen-bonded guanine bases. Accumulating studies
      have revealed that G-quadruplex structures are formed in vivo and play important
      roles in biological processes such as DNA replication, transcription,
      recombination, epigenetic regulation, meiosis, antigenic variation, and
      maintenance of telomeres stability. Mounting evidence indicates that a variety of
      proteins are capable of binding selectively and tightly to G-quadruplex and play
      essential roles in G-quadruplex-mediated regulation processes. Some of these
      proteins promote the formation or/and stabilization of G-quadruplex, while some
      other proteins act to unwind G-quadruplex preferentially. From a drug discovery
      perspective, many of these G-quadruplex binding proteins and/or their complexes
      with G-quadruplexes are potential drug targets. Here, we present a general
      summary of reported G-quadruplex binding proteins and their biological functions,
      with focus on those of medicinal research significance. We elaborated the
      possibility for some of these G-quadruplex binding proteins and their complexes
      with G-quadruplexes as potential drug targets.

PMID- 25980413
TI  - A Fluorescent Anti-Cancer Agent, 3,6-bis(1-methyl-4-vinylpyridinium) Carbazole
      Diiodide, Stains G-Quadruplexes in Cells and Inhibits Tumor Growth.
AB  - Compelling evidence suggests that formation of guanine-quadruplex (G4) can
      protect the integrity of chromosome ends in eukaryotes, and regulate the activity
      of some gene promoters. In addition, G4 may be a novel therapeutic target. Thus,
      a number of ligands have been synthesized to stabilize G4. However, skepticism
      lingers over the existence of G4 in cells, as well as its biological function.
      The molecule 3,6-bis(1-methyl-4-vinylpyridium) carbazole diiodide (BMVC) can be
      used not only as a fluorescent probe to map endogenous and exogenous G4 in live
      cells, but also as therapeutic agent that arrests cancer growth by inhibiting
      telomerase activity and regulating gene expression. Thus, the fluorescence of a
      G4 anti-cancer agent is an invaluable tool to detect G4 in cells, investigate
      ligand-G4 interaction in live cells, examine the biological function of G4, and
      guide the development of new fluorescent anti-cancer agents. 

PMID- 25980414
TI  - Recent Development of G-Quadruplex Probes for Cellular Imaging.
AB  - The G-quadruplex structure is a non-canonical secondary DNA motif that is built
      from planar tetrads of guanine residues stabilized by Hoogsteen-type hydrogen
      bonding. Bioinformatics studies indicate that sequences rich in guanine that are
      able to form G-quadruplexes are widely distributed throughout the human genome,
      particularly in telomere and promoter regions of genes. G-quadruplex sequences
      found in the promoters of human oncogenes, such as k-ras, c-myc and bcl-2 have
      attracted particular attention as molecular targets for therapeutic intervention
      due to their potential capability to regulate gene expression at the
      transcriptional level. Moreover, the G-quadruplex structure has been associated
      with a number of human diseases arising from defective telomeric maintenance.
      Despite intensive research in this area, however, the actual function of G
      quadruplexes in vivo has not yet been fully understood. Therefore, significant
      efforts have been devoted to the discovery of specific probes for visualizing and
      distinguishing G-quadruplex structures from other nucleic acid molecules likely
      to be found in biological environments. This review summarizes recent studies in
      the development of G-quadruplex probes over the past three years, with a
      particular emphasize on the detection and imaging of G-quadruplex structures
      within living cells. Furthermore, the detection and biological relevance of RNA G
      quadruplexes is discussed. 

PMID- 25980415
TI  - RNA G-Quadruplex: The New Potential Targets for Therapy.
AB  - Roles of RNA on transcriptional and post-transcriptional regulations have raised
      more attention since the new era of genomics. One of the secondary structures of
      RNA, the RNA Gquadruplex structure, is demonstrated a relatively stable existence
      in human tumor cells, virus, or other species relating to diseases. G
      quadruplexes are special secondary structures formed by G-rich DNA and RNA
      sequences that fold into a four-stranded conformation. The G-quadruplexes formed
      in RNA are involved in many biological process including telomere elongation,
      transcription regulate, pre-mRNA splicing and translation. In this review, we
      will give a brief introduction to the structures of RNA G-quadruplexes, the
      biological roles and the potential to be as drug targets. 

PMID- 25980416
TI  - Telomere G-Quadruplex as a Potential Target to Accelerate Telomere Shortening by
      Expanding the Incomplete End-Replication of Telomere DNA.
AB  - Chromosomes in human cells are protected by telomeres. Telomere shortens during
      each round of cell division because of the DNA end-replication problem. Cancer
      cells maintain telomere length homeostasis by either telomerase or/and the
      alternative lengthening of telomere (ALT) mechanism to sustain their division
      potential. Telomeric DNA tends to form G-quadruplex preferentially at the extreme
      3' end. This unique feature prevents the 3' end from being used as a substrate of
      telomerase and as a primer in the ALT. Therefore, stabilizing telomere G
      quadruplex is expected to inhibit both pathways and limit the proliferation of
      cancer cells. Based on a mathematical modeling and experimental results, this
      mini-review proposes a hypothesis that the formation of G-quadruplex in telomere
      may constitute a significant contribution to the incomplete end-replication of
      telomere DNA by preventing the priming of DNA synthesis near the 3' end during
      telomere replication. According to this, stabilization of telomere G-quadruplex
      by chemical ligand may promise to accelerate telomere shortening in proliferating
      cells. 

PMID- 25980418
TI  - The Spatial Epidemiology of Intimate Partner Violence: Do Neighborhoods Matter?
AB  - We examined whether neighborhood-level characteristics influence spatial
      variations in the risk of intimate partner violence (IPV). Geocoded data on IPV
      cases with associated protection orders (n = 1,623) in the city of Valencia,
      Spain (2011-2013), were used for the analyses. Neighborhood units were 552 census
      block groups. Drawing from social disorganization theory, we explored 3 types of
      contextual influences: concentrated disadvantage, concentration of immigrants,
      and residential instability. A Bayesian spatial random-effects modeling approach
      was used to analyze influences of neighborhood-level characteristics on small
      area variations in IPV risk. Disease mapping methods were also used to visualize
      areas of excess IPV risk. Results indicated that IPV risk was higher in
      physically disordered and decaying neighborhoods and in neighborhoods with low
      educational and economic status levels, high levels of public disorder and crime,
      and high concentrations of immigrants. Results also revealed spatially structured
      remaining variability in IPV risk that was not explained by the covariates. In
      this study, neighborhood concentrated disadvantage and immigrant concentration
      emerged as significant ecological risk factors explaining IPV. Addressing
      neighborhood-level risk factors should be considered for better targeting of IPV
      prevention. 

PMID- 25980419
TI  - [Author's reply].

PMID- 25980420
TI  - Herb-drug interactions between Scutellariae Radix and mefenamic acid:
      Simultaneous investigation of pharmacokinetics, anti-inflammatory effect and
      gastric damage in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Scutellariae Radix (SR), the dried root of
      Scutellariae baicalensis Georgi, has a lot in common with non-steroidal anti
      inflammatory drugs (NSAIDs). Their similarities in therapeutic action (anti
      inflammation) and metabolic pathways (phase II metabolisms) may lead to co
      administration by patients with the potential of pharmacokinetic and/or
      pharmacodynamic interactions. The current study aims to investigate the potential
      interactions between SR and an NSAID, mefenamic acid (MEF), on the overall
      pharmacokinetic dispositions, anti-inflammatory effects and adverse effects in
      rats. MATERIALS AND METHODS: The current study simultaneously monitored the
      pharmacokinetic and pharmacodynamic interactions in a single animal. Four groups
      of Sprague-Dawley rats (n=7 each) received oral doses of a standardized SR
      extract (300mg/kg, twice daily), MEF (40mg/kg, daily), combination of SR extract
      and MEF, and vehicle control, respectively, for 5 days. On Day 5, blood samples
      were collected after first dose over 24h for the determination of (1) plasma
      concentrations of SR bioactive components, MEF and its metabolites by LC-MS/MS,
      and (2) prostaglandin E2 (PGE2) production and cyclooxygenase-2 (COX-2) gene
      expression by ex vivo analyses using LPS-stimulated RAW264.7 macrophage cells,
      ELISA and real time-PCR. After the rats were sacrificed, stomachs were isolated
      to assess their gross mucosal damage. Statistical comparisons were conducted
      using ANOVA and t-test. RESULTS: Minimal pharmacokinetic interaction between SR
      extract and MEF was observed. Co-administration of SR extract and MEF did not
      significantly alter the plasma concentration-time profile or the pharmacokinetic
      parameters such as Cmax, AUC0->24, Tmax or clearance. Pharmacodynamic interaction
      via the COX-2 pathway was observed. The PGE2 level in LPS-stimulated RAW264.7
      cells treated with plasma collected from control group over the 24h sampling
      (AUC0->24[PGE2]) was 191981+/-8789pg/mlhr, which was significantly reduced to
      174,780+/-6531 and 46,225+/-1915pg/mlhr by plasma collected from rats
      administered with SR extract and MEF, respectively. Co-administration of SR
      extract and MEF further potentiated the PGE2 inhibition, with an AUC0->24[PGE2]
      of 37013+/-2354pg/mlhr (p<0.05, compared to SR or MEF group). By analyzing the
      COX-2 gene expression, SR extract significantly prolonged the COX-2 inhibitory
      effect of MEF over the 24h (p<0.05). Furthermore, the MEF-induced stomach ulcer
      after the 5-day treatment, as evidenced by the increased gross ulcer index and
      sum of lesion length (p<0.05, compared to control), could be alleviated by co
      administration with SR extract (p<0.05). CONCLUSIONS: Co-administration of SR
      extract and MEF potentiated the anti-inflammatory effects, alleviated the MEF
      induced stomach adverse effect while having minimal pharmacokinetic interactions.
      Our findings provide insight for combination therapy of SR extract and MEF
      against inflammatory diseases.

PMID- 25980421
TI  - An extract of Artemisia dracunculus L. stimulates insulin secretion from beta
      cells, activates AMPK and suppresses inflammation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia dracunculus L. (Russian tarragon) is a
      perennial herb belonging to the family Compositae and has a history of medicinal
      use in humans, particularly for treatment of diabetes. AIM OF THE STUDY: In this
      study a defined plant extract from A. dracunculus L. (termed PMI-5011) is used to
      improve beta(beta) cells function and maintain beta cell number in pancreatic
      islets as an alternative drug approach for successful treatment of diabetes.
      MATERIALS AND METHODS: Mouse and human pancreatic beta cells were treated with
      defined plant extract of A. dracunculus L. (PMI-5011) to understand the
      mechanism(s) that influence beta cell function and beta cell number. RESULTS: We
      found that the PMI-5011 enhances insulin release from primary beta cells,
      isolated mouse and human islets and it maintains beta cell number. Insulin
      released by PMI-5011 is associated with the activation of AMP-activated protein
      kinase (AMPK), and protein kinase B (PKB). Furthermore, PMI-5011 suppresses
      LPS/INFgamma-induced inflammation and inflammatory mediator(s) in macrophages.
      PMI-5011 inhibited Nitric oxide (NO) production and expression of inducible
      nitric oxide synthase (iNOS) at the protein level and also attenuated pro
      inflammatory cytokine (IL-6) production in macrophages. CONCLUSION: PMI-5011 has
      potential therapeutic value for diabetes treatment via increasing insulin release
      from beta cells and decreases capacity of macrophages to combat inflammation.

PMID- 25980422
TI  - Effects of Gancao on pharmacokinetic profiles of platycodin D and deapio
      platycodin D in Jiegeng.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jiegeng (Radix Platycodi), the dried root of
      Platycodon grandiflorum A. DC (Campanulaceae), has been used to treat cough, sore
      throat, bronchitis, and bronchial asthma for thousands of years. It is commonly
      prescribed with Gancao (Radix et Rhizoma Glycyrrhizae) as a herbal combination in
      traditional Chinese medicine (TCM) to produce synergistic effects. AIM OF THE
      STUDY: To elucidate the herbaceous compatibility of Jiegeng and Gancao, we
      investigated the comparative pharmacokinetics, intestinal absorption, and
      microbial metabolism of platycodin D (PD) and deapio-platycodin D (DPD), the
      platycodins contained in Jiegeng. MATERIALS AND METHODS: In the comparative
      pharmacokinetic study, the concentrations of PD and DPD in Jiegeng extract (JE)
      and the Jiegeng-Gancao herb pair (JGHP) were determined in rat plasma using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, the main
      pharmacokinetic parameters were calculated using data analysis software (DAS).
      Furthermore, in vitro studies using Caco-2 cells and fecal lysates were performed
      to contradistinguish the intestinal absorption and microbial metabolism of PD and
      DPD in JE from those in JGHP. RESULTS: The peak concentration (Cmax) and area
      under the plasma concentration curve (AUC) of PD in rats orally administrated
      JGHP significantly increased compared to that in rats treated with JE. In
      addition, the time to reach peak concentration (Tmax) and half-life (t1/2) of PD
      and DPD in combination with JGHP were all prolonged compared with those of JE.
      There was no significant difference in the absorption of PD between JE and JGHP
      in Caco-2 cells. However, the hydrolysis of both PD and DPD in JGHP were weaker
      than that in JE after a 2-h incubation in fecal lysate which might be responsible
      for the different pharmacokinetic profiles of the platycodins in JE and JGHP.
      CONCLUSION: In this study, we discovered that Gancao might influence the
      pharmacokinetic profiles of PD and DPD in Jiegeng. Furthermore, the difference in
      profiles may be attributable to the inequable microbial metabolism rather than
      intestinal absorption of the platycodins in JE and JGHP. The results of this
      study elucidated the pharmacokinetic compatibility and rationale for the use of
      JGHP.

PMID- 25980423
TI  - Evaluation of antiplasmodial and antileishmanial activities of herbal medicine
      Pseudelephantopus spiralis (Less.) Cronquist and isolated hirsutinolide-type
      sesquiterpenoids.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pseudelephantopus spiralis (Less.) Cronquist is
      distributed in the Caribbean, Mesoamerica and Latin America. Preparations of the
      plant are traditionally used in Latin America for the treatment of various
      diseases including fever, malaria, and spleen or liver inflammations. MATERIALS
      AND METHODS: Aerial parts of P. spiralis were extracted with either ethanol or
      distilled water. Seven hirsutinolide-type sesquiterpenoids were isolated: 8
      acetyl-13-ethoxypiptocarphol (1), diacetylpiptocarphol (2), piptocarphins A (3),
      F (4) and D (5), (1S(*),4R(*),8S(*),10R(*))-1,4-epoxy-13-ethoxy-1,8,10
      trihydroxygermacra-5E,7(11)-dien-6,12-olide (6), and piptocarphol (7). Extracts
      and isolated compounds (2, 3, 5-7) were screened for their in vitro
      antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum
      strain FcM29-Cameroon and antileishmanial activity against three stages of
      Leishmania infantum. Their cytotoxicities were also evaluated against healthy
      VERO cell lines and J774A.1 macrophages, the host cells of the Leishmania
      parasites in humans. RESULTS: Aqueous extracts showed a greater inhibitory effect
      than alcoholic extracts, with IC50 on P. falciparum of 3.0ug/mL versus 21.1ug/mL,
      and on L. infantum of 13.4ug/mL versus >50ug/mL. Both extracts were found to be
      cytotoxic to VERO cells (CC50<3ug/mL). Sesquiterpene lactones 2 and 3 showed the
      best activity against both parasites but failed in selectivity. Carbon 8
      hydroxylated hirsutinolides 5-7 presented the particularity of exhibiting two
      conformers observed in solution during extensive NMR analyses in CD3OD and UHPLC
      MS. The presence of a hydroxyl function at C-8 decreased the activity of 5-7 on
      the two parasites and also on VERO cells. CONCLUSION: The antiplasmodial activity
      displayed by the aqueous extract explains the traditional use of P. spiralis in
      the treatment of malaria. This activity seems to be attributable to the presence
      of sesquiterpene lactones 2 and 3, the most active against P. falciparum. Aqueous
      extract and compounds 2, 3 and 6 were also active against L. infantum but lacked
      in selectivity due to their cytotoxicity towards macrophages. Exploring the
      safety and antiplasmodial efficacy of this traditional remedy will require
      further toxicological and in vivo studies in the light of the cytotoxicity
      towards healthy cell lines displayed by the aqueous extract and compounds 2 and
      3.

PMID- 25980424
TI  - Involvement of monoaminergic systems in the antidepressant-like properties of
      Lafoensia pacari A. St. Hil.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lafoensia pacari A. St.-Hil. (Lythraceae), known
      popularly as "pacari" or "mangaba-brava" is popularly used in the state of Goias,
      Brazil. The stem bark or leaves are used to treat cancer, gastric disorders,
      inflammation and as a tonic to treat loss of enthusiasm. AIM OF THE STUDY:
      Previous results suggest that the ethanol:water 7:3 extract of the stem bark of
      L. pacari (PEx) has antidepressant-like activity in male mice. Our aim was to
      perform the PEx's bioguided fractionation and evaluate the monoaminergic system
      involvement in the antidepressant effect as well as progress in the study of L.
      pacari mechanism of action. MATERIAL AND METHODS: Mice (30-35g) orally treated
      (24, 5 and 1h) with PEx (100, 300 or 1000mg/kg), chloroform (ChloF-70mg/kg),
      ethyl acetate (180mg/kg), n-butanol (370mg/kg) and aqueous (1g/kg) fractions were
      submitted to the forced swimming test. To assess the mechanism of action,
      different groups of mice were pretreated with p-chlorophenylalanine (PCPA
      100mg/kg, 4 days, i.p.) and alpha-methyl-p-tyrosine (AMPT-100mg/kg, 4h, i.p.) to
      assess the involvement of serotoninergic and catecholaminergic systems in the
      ChloF effects, respectively. A putative in vitro inhibition of monoamine oxidase
      (MAO) activity as well as the ex vivo hippocampal brain-derived neurotrophic
      factor (BDNF) quantification were carried out. Phytochemical screening,
      spectroscopy and chromatography analysis were used for identification of
      compounds present in ChloF. RESULTS AND DISCUSSION: After the fractionation, the
      ChloF 70mg/kg was the most active fraction, reducing the immobility time by 22%.
      Pre-treatments with both PCPA and AMPT abolished the ChloF effects, suggesting
      that ChloF antidepressant-like effect is dependent on serotonergic and
      catecholaminergic systems. ChloF did not inhibited MAO-A or MAO-B activity,
      excluding this as possible mechanism of action. ChloF augmented hippocampal BDNF
      level, which could be accounted for its antidepressant-like effect. Phytochemical
      screening showed the presence of saponins, tannins, steroids and triterpene in
      the PEx, and the presence of triterpene and steroids in ChloF. The spectroscopy
      and chromatography analysis identified lupeol, beta-sitosterol and stigmasterol
      in ChloF. CONCLUSION: ChloF is the fraction that better retained the crude
      extract active constituents. ChloF presents antidepressant-like effect that
      involves both serotonergic and catecholaminergic systems without inhibiting MAO
      enzymatic activity; this fraction also increases the hippocampal BDNF levels.

PMID- 25980425
TI  - Inactivated and subunit vaccines against porcine reproductive and respiratory
      syndrome: Current status and future direction.
AB  - Within a few years of its emergence in the late 1980s, the PRRS virus had spread
      globally to become the foremost infectious disease concern for the pork industry.
      Since 1994, modified live-attenuated vaccines against porcine reproductive and
      respiratory syndrome virus (PRRSV-MLV) have been widely used, but have failed to
      provide complete protection against emerging and heterologous field strains of
      the virus. Moreover, like many other MLVs, PRRSV-MLVs have safety concerns
      including vertical and horizontal transmission of the vaccine virus and several
      documented incidences of reversion to virulence. Thus, the development of
      efficacious inactivated vaccines is warranted for the control and eradication of
      PRRS. Since the early 1990s, researchers have been attempting to develop
      inactivated PRRSV vaccines, but most of the candidates have failed to elicit
      protective immunity even against homologous virus challenge. Recent research
      findings relating to both inactivated and subunit candidate PRRSV vaccines have
      shown promise, but they need to be pursued further to improve their heterologous
      efficacy and cost-effectiveness before considering commercialization. In this
      comprehensive review, we provide information on attempts to develop PRRSV
      inactivated and subunit vaccines. These includes various virus inactivation
      strategies, adjuvants, nanoparticle-based vaccine delivery systems, DNA vaccines,
      and recombinant subunit vaccines produced using baculovirus, plant, and
      replication-deficient viruses as vector vaccines. Finally, future directions for
      the development of innovative non-infectious PRRSV vaccines are suggested.
      Undoubtedly there remains a need for novel PRRSV vaccine strategies targeted to
      deliver cross-protective, non-infectious vaccines for the control and eradication
      of PRRS.

PMID- 25980426
TI  - Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23
      valent pneumococcal polysaccharide vaccine administration in older adults.
AB  - BACKGROUND: Concomitant administration of influenza and pneumococcal vaccines
      facilitates their uptake by older adults; however, data on immunogenicity and
      safety of concomitant administration of adjuvanted trivalent inactivated
      influenza vaccine (aIIV3) and 23-valent pneumococcal polysaccharide vaccine
      (PPSV23) have not been reported. METHODS: Subjects aged >=65 years (N=224) were
      randomized 1:1:1:1 to receive MF59-aIIV3 alone, MF59-aIIV3+PPSV23 in
      contralateral arms, MF59-aIIV3+PPSV23 in the same arm or PPSV23 alone (Clinical
      Trial Number - NCT02225327). Hemagglutination inhibition assay and multiplex
      opsonophagocytic killing assay were used to compare immunogenicity after single
      or concomitant vaccination. RESULTS: All groups met immunogenicity criteria for
      the influenza vaccine in older adults with similar seroconversion rates and
      geometric mean fold-increases, irrespective of concomitant vaccinations and
      injection site. For each pneumococcal serotype, opsonic index (OI) increased
      markedly after the PPSV23 vaccination, irrespective of the concomitant influenza
      vaccine. All subjects showed an OI>=8 for serotypes 6B, 18C and 19A post
      vaccination, with a suggestion that the ipsilateral concomitant vaccination might
      be associated with higher OIs for some antigens. Local and systemic adverse
      events were more common in subjects receiving PPSV23 compared to those receiving
      aIIV3 alone. CONCLUSIONS: No interference was observed with antibody responses to
      influenza or pneumococcal antigens when aIIV3 and PPSV23 were administered
      concomitantly.

PMID- 25980427
TI  - Classical swine fever virus marker vaccine strain CP7_E2alf: Shedding and
      dissemination studies in boars.
AB  - Over the last decade, pestivirus chimaera CP7_E2alf has proven to be a most
      promising marker vaccine candidate against classical swine fever (CSF). To
      provide further background data for the risk assessment towards licensing and
      release, especially on presence of the vaccine chimaera in faeces, urine, and
      organs of the male reproductive tract, supplementary studies were carried out
      under controlled laboratory conditions. In detail, the shedding and dissemination
      pattern of Suvaxyn((r)) CSF Marker ("CP7_E2alf") was assessed in 12 adult boars
      after single intramuscular vaccination with a tenfold vaccine dose. Four and
      seven days post vaccination, six animals were subjected to necropsy and
      triplicate samples were obtained from reproductive and lymphatic organs as well
      as urine, faeces, blood, and several additional organs and matrices. The sampling
      days were chosen based on pre-existing data that indicated the highest
      probability of virus detection. Upon vaccination, neither local nor systemic
      adverse effects were observed in the experimental animals. It was confirmed that
      primary replication is restricted to the lymphatic tissues and especially the
      tonsil. While viral genome was detectable in several samples from lymphatic
      tissues at four and seven days post vaccination, infectious virus was only
      demonstrated at four days post vaccination in one tonsil sample and one parotid
      lymphnode. Sporadic detection at a very low level occurred in some replicates of
      liver, lung, bone marrow, and salivary gland samples. In contrast, viral genome
      was not detected in any sample from reproductive organs and accessory sex glands,
      in faeces, urine, or bile. The presented data on the dissemination of the vaccine
      virus CP7_E2alf in adult boars are supplementing existing safety and efficacy
      studies and indicate that the use of the vaccine is also safe in reproductive
      boars.

PMID- 25980429
TI  - Vaccination errors reported to the Vaccine Adverse Event Reporting System,
      (VAERS) United States, 2000-2013.
AB  - IMPORTANCE: Vaccination errors are preventable events. Errors can have impacts
      including inadequate immunological protection, possible injury, cost,
      inconvenience, and reduced confidence in the healthcare delivery system.
      OBJECTIVES: To describe vaccination error reports submitted to the Vaccine
      Adverse Event Reporting System (VAERS) and identify opportunities for prevention.
      METHODS: We conducted descriptive analyses using data from VAERS, the U.S.
      spontaneous surveillance system for adverse events following immunization. The
      VAERS database was searched from 2000 through 2013 for U.S. reports describing
      vaccination errors and reports were categorized into 11 error groups. We analyzed
      numbers and types of vaccination error reports, vaccines involved, reporting
      trends over time, and descriptions of errors for selected reports. RESULTS: We
      identified 20,585 vaccination error reports documenting 21,843 errors. Annual
      reports increased from 10 in 2000 to 4324 in 2013. The most common error group
      was "Inappropriate Schedule" (5947; 27%); human papillomavirus (quadrivalent)
      (1516) and rotavirus (880) vaccines were most frequently involved. "Storage and
      Dispensing" errors (4983; 23%) included mostly expired vaccine administered
      (2746) and incorrect storage of vaccine (2202). "Wrong Vaccine Administered"
      errors (3372; 15%) included mix-ups between vaccines with similar antigens such
      as varicella/herpes zoster (shingles), DTaP/Tdap, and pneumococcal
      conjugate/polysaccharide. For error reports with an adverse health event (5204;
      25% of total), 92% were classified as non-serious. We also identified 936
      vaccination error clusters (i.e., same error, multiple patients, in a common
      setting) involving over 6141 patients. The most common error in clusters was
      incorrect storage of vaccine (582 clusters and more than 1715 patients).
      CONCLUSIONS: Vaccination error reports to VAERS have increased substantially.
      Contributing factors might include changes in reporting practices, increasing
      complexity of the immunization schedule, availability of products with similar
      sounding names or acronyms, and increased attention to storage and temperature
      lapses. Prevention strategies should be considered.

PMID- 25980428
TI  - Cost-effectiveness of norovirus vaccination in children in Peru.
AB  - BACKGROUND: With candidate norovirus (NV) vaccines in a rapid phase of
      development, assessment of the potential economic value of vaccine implementation
      will be necessary to aid health officials in vaccine implementation decisions. To
      date, no evaluations have been performed to evaluate the benefit of adopting NV
      vaccines for use in the childhood immunization programs of low- and middle-income
      countries. METHODS: We used a Markov decision model to evaluate the cost
      effectiveness of adding a two-dose NV vaccine to Peru's routine childhood
      immunization schedule using two recent estimates of NV incidence, one for a peri
      urban region and one for a jungle region of the country. RESULTS: Using the peri
      urban NV incidence estimate, the annual cost of vaccination would be $13.0
      million, offset by $2.6 million in treatment savings. Overall, this would result
      in 473 total DALYs averted; 526,245 diarrhea cases averted;153,735 outpatient
      visits averted; and 414 hospitalizations averted between birth and the fifth year
      of life. The incremental cost-effectiveness ratio would be $21,415 per DALY
      averted; $19.86 per diarrhea case; $68.23 per outpatient visit; and $26,298 per
      hospitalization. Using the higher jungle NV incidence rates provided a lower cost
      per DALY of $10,135. The incremental cost per DALY with per-urban NV incidence is
      greater than three times the 2012 GDP per capita of Peru but the estimate drops
      below this threshold using the incidence from the jungle setting. In addition to
      the impact of incidence, sensitivity analysis showed that vaccine price and
      efficacy play a strong role in determining the level of cost-effectiveness.
      CONCLUSIONS: The introduction of a NV vaccine would prevent many healthcare
      outcomes in the Peru and potentially be cost-effective in scenarios with high NV
      incidence. The vaccine cost-effectiveness model could also be applied to the
      evaluation of NV vaccine cost-effectiveness in other countries. In resource-poor
      settings, where NV incidence rates are expected to be higher.

PMID- 25980430
TI  - The site of administration influences both the type and the magnitude of the
      immune response induced by DNA vaccine electroporation.
AB  - We investigated the influence of the site of administration of DNA vaccine on the
      induced immune response. DNA vaccines were administered by electroporation at
      three different sites: tibial cranial muscle, abdominal skin and ear pinna.
      Aiming to draw general conclusions about DNA vaccine delivery, we successively
      used several plasmids encoding either luciferase and ovalbumin as models or gp160
      and P1A as vaccines against HIV and P815 mastocytoma, respectively. Low levels
      and duration of luciferase transgene expression were observed after
      electroporation of the abdominal skin, partly explaining its lower immunogenic
      performance as compared to the other sites of administration. Analyses of OT-I
      CD8+ and OT-II CD4+ T cell responses highlighted the differential impact of the
      delivery site on the elicited immune response. Muscle electroporation induced the
      strongest humoral immune response and both muscle and ear pinna sites induced
      cellular immunity against gp160. Ear pinna delivery generated the highest level
      of CTL responses against P1A but electroporation of muscle and ear pinna were
      equally efficient in delaying P815 growth and improving mice survival. The
      present study demonstrated that the site of administration is a key factor to be
      tested in the development of DNA vaccine. 

PMID- 25980431
TI  - High-Flow Nasal Cannulae or Noninvasive Ventilation for Management of
      Postoperative Respiratory Failure.

PMID- 25980432
TI  - TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick
      ascending limbs.
AB  - Medullary thick ascending limbs (mTAL) regulate Na balance and therefore blood
      pressure. We previously showed that cell swelling and luminal flow activates the
      mechanosensitive channel TRPV4 in mTAL. AIM: We hypothesized that TRPV4 mediates
      flow-induced increases in intracellular Ca (Cai) in rat mTALs. METHODS: We
      performed ratiometric measurements of Cai in perfused mTALs. RESULTS: Increasing
      luminal flow from 0 to 20 nL min(-1) caused Cai to peak 231 +/- 29 nmol L(-1)
      above basal concentrations (n = 18). The general TRPV inhibitor ruthenium red at
      15 and 50 MUmol L(-1) reduced peak Cai by 41 +/- 9 (P < 0.01; n = 5) and 77 +/-
      10% (P < 0.02; n = 6). The selective TRPV4 inhibitor RN1734 at 10 and 50 MUmol L(
      1) reduced peak Cai by 46 +/- 11 (P < 0.01; n = 7) and 76 +/- 5% (P < 0.02; n =
      5) respectively. To specifically target TRPV4, mTALs were transduced with
      adenoviruses expressing TRPV4 small hairpin (sh) RNA. In non-transduced control
      mTALs, luminal flow generated a peak increase in Cai of 111 +/- 21 nmol L(-1) (n
      = 8). In TRPV4shRNA-transduced mTALs, the Cai peak was reduced to 56 +/- 8 nmol
      L(-1) (P < 0.03, n = 9). Removing extracellular Ca completely abolished flow
      induced increases in Cai. Increasing luminal flow in the presence of hexokinase
      20 (U mL(-1) ) to scavenge extracellular ATP did not modify significantly the
      increases in Cai induced by luminal flow. Finally, we studied the effect of the
      TRPV4 selective agonist GSK1016790A on Cai. In the absence of luminal flow,
      GSK1016790A (10 nmol L(-1) ) increased Cai from 60 +/- 11 nmol L(-1) to 262 +/-
      71 nmol L(-1) (P < 0.05; n = 7). CONCLUSION: We conclude that flow-induced
      increases in Cai are mediated primarily by TRPV4 in the rat mTAL.

PMID- 25980433
TI  - The Comparative Burden of Chronic Widespread Pain and Fibromyalgia in the United
      States.
AB  - BACKGROUND/PURPOSE: Little information exists on the comparative patient and
      economic burden of chronic widespread pain (CWP) and fibromyalgia (FM) in the
      United States. METHODS: This multistage, observational study included an online
      screening survey of a large geographically diverse US sample to assess CWP
      status, a physician/site visit to determine FM diagnosis, and an online subject
      questionnaire to capture clinical characteristics, pain, health status,
      functioning, sleep, healthcare resource use (HRU), productivity, and costs. Based
      on the screener and physician evaluation, mutually exclusive groups of subjects
      without CWP (CWP-), with CWP but without FM (CWP+), and with confirmed FM were
      identified. RESULTS: Disease burden was examined in 472 subjects (125 CWP-, 176
      CWP+, 171 FM). Age, race, and ethnicity were similar across groups. Mean body
      mass index and number of comorbidities increased from CWP- to CWP+ to FM (P =
      0.0044, P < 0.0001, respectively). From CWP- to CWP+ to FM, there were reductions
      in health status (EQ-5D, SF-12) and sleep outcomes (MOS-SS, SSQ) (all P < 0.05).
      Pain severity, interference with function (BPI-SF), and overall work impairment
      (WPAI:SHP) increased from CWP- to CWP+ to FM (all P < 0.0001). Higher proportions
      of CWP+ (52.8%) and FM subjects (62.6%) were taking pain-related prescription
      medications relative to CWP- subjects (32.8%; P < 0.0001). Significant
      differences in total direct and indirect costs across the three groups (both P <
      0.0001) were observed, with highest costs among FM subjects. CONCLUSION:
      Fibromyalgia subjects were characterized by the greatest disease burden with more
      comorbidities and pain-related medications, poorer health status, function,
      sleep, lower productivity, and higher costs.

PMID- 25980434
TI  - Nurse-Led Trauma-Informed Correctional Care for Women.
AB  - PURPOSE: Incarcerated women are a vulnerable and unique population of special
      concern to nurses as they have high rates of mental illness. In this article, the
      authors discuss how trauma exposure contributes to mental illness in incarcerated
      women through abuse, socioeconomic factors, and the prison environment, how this
      trauma exposure manifests in the inmate survivor, and the related implications
      for practice. CONCLUSIONS: A history of trauma and victimization is related to
      complex mental health issues which affect the majority of justice-involved women.
      The correctional environment can exacerbate these issues. PRACTICE IMPLICATIONS:
      Nursing implications include discussion of the trauma-informed care model. The
      authors recommend a model of trauma-informed care named "the 4 Es" that can guide
      nurses in preparing a trauma-informed correctional environment and discuss the
      importance of nurse-led policy change in finding alternatives to incarceration
      for women with mental illness.

PMID- 25980436
TI  - SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets
      Cyclin D2 through H4K20me3.
AB  - Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical
      and pathological parameters have limited ability to discriminate between
      clinically significant and indolent PCa. Altered expression of histone
      methyltransferases and histone methylation patterns are involved in prostate
      carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate
      among PCa with different clinical aggressiveness, so we decided to investigate
      its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact
      through in vitro (cell viability, cell cycle, apoptosis, migration, invasion
      assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's
      impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target
      genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant
      phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed
      phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect
      is mediated through its histone methyltransferase activity. Moreover, CCND2 was
      identified as a putative target gene for SMYD3 transcriptional regulation,
      through trimethylation of H4K20.Our results support a proto-oncogenic role for
      SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic
      activity. Thus, SMYD3 overexpression is a potential biomarker for clinically
      aggressive disease and an attractive therapeutic target in PCa. 

PMID- 25980435
TI  - YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic
      factors into the extracellular microenvironment.
AB  - Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which
      confers mesenchymal cell properties, such as reduced cell-cell contact and
      increased cell migration and invasion, to epithelial cells. Here we investigate
      the role of the pleiotropic transcription/splicing factor and RNA-binding protein
      nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in increasing the
      oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells
      expressing YBX1 (MDCKYBX1 cells) revealed a partial EMT phenotype, including
      cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage
      independent growth. Subcutaneous injection of parental MDCK cells into NOD/SCID
      mice did not form tumours. Critically, MDCKYBX1 cells established viable tumour
      xenografts, and immuno-histochemical staining indicated murine vascularization by
      CD31+ endothelial cells. We analysed the total secretome (containing soluble and
      extracellular vesicles) of MDCKYBX1 cells to investigate regulation of the tumour
      microenvironment. YBX1 expression elevated release of secreted factors known to
      enhance angiogenesis (TGF-beta, CSF-1, NGF, VGF, ADAM9 and ADAM17), compared to
      MDCK cells. Importantly, treatment with MDCKYBX1 cell-derived secretome increased
      recipient 2F-2B endothelial cell motility. This defines YBX1 as an oncogenic
      enhancer that can regulate tumour angiogenesis via release of secreted modulators
      into the extracellular microenvironment. 

PMID- 25980438
TI  - A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent
      antitumor efficacy in hepatocellular carcinoma.
AB  - Golgi apparatus is the organelle mainly functioning as protein processing and
      secretion. GOLPH2 is a resident Golgi glycoprotein, usually called GP73. Recent
      data displayed that GOLPH2 is a superb hepatocellular carcinoma (HCC) marker
      candidate, and even its specificity is better than liver cancer marker AFP.
      Oncolytic adenoviruses are broadly used for targeting cancer therapy due to their
      selective tumor-killing effect. However, it was reported that traditionally
      oncolytic adenovirus lack the HCC specificity. In this study, a novel dual
      regulated oncolytic adenovirus GD55 targeting HCC was first constructed based on
      our cancer targeted gene-viral therapeutic strategy. To verify the targeting and
      effectiveness of GOLPH2-regulated oncolytic adenovirus GD55 in HCC, the
      anticancer capacity was investigated in HCC cell lines and animal model. The
      results proved that the novel GOLPH2-regulated GD55 conferred higher adenovirus
      replication and infectivity for liver cancer cells than oncolytic adenovirus
      ZD55. The GOLPH2-regulated GD55 exerted a significant grow-suppressing effect on
      HCC cells in vitro but little damage to normal liver cells. In animal experiment,
      antitumor effect of GD55 was more effective in HCC xenograft of nude mice than
      that of ZD55. Thus GOLPH2-regulated GD55 may be a promising oncolytic virus agent
      for future liver cancer treatment. 

PMID- 25980437
TI  - Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma
      identifies a mutation-based prognostic gene signature.
AB  - BACKGROUND: Patients with advanced oral squamous cell carcinoma (OSCC) have
      heterogeneous outcomes that limit the implementation of tailored treatment
      options. Genetic markers for improved prognostic stratification are eagerly
      awaited. METHODS: Herein, next-generation sequencing (NGS) was performed in 345
      formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC
      patients. Genetic mutations on the hotspot regions of 45 cancer-related genes
      were detected using an ultra-deep (>1000*) sequencing approach. Kaplan-Meier
      plots and Cox regression analyses were used to investigate the associations
      between the mutation status and disease-free survival (DFS). RESULTS: We
      identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA,
      CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14
      genes were found to predict DFS. A mutation-based signature affecting ten genes
      (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was
      devised to predict DFS. Two different resampling methods were used to validate
      the prognostic value of the identified gene signature. Multivariate analysis
      demonstrated that presence of a mutated gene signature was an independent
      predictor of poorer DFS (P = 0.005). CONCLUSIONS: Genetic variants identified by
      NGS technology in FFPE samples are clinically useful to predict prognosis in
      advanced OSCC patients.

PMID- 25980439
TI  - Loss of TFF1 promotes Helicobacter pylori-induced beta-catenin activation and
      gastric tumorigenesis.
AB  - Using in vitro and in vivo models, we investigated the role of TFF1 in
      suppressing H. pylori-mediated activation of oncogenic beta-catenin in gastric
      tumorigenesis. A reconstitution of TFF1 expression in gastric cancer cells
      decreased H. pylori-induced beta-catenin nuclear translocation, as compared to
      control (p < 0.001). These cells exhibited significantly lower beta-catenin
      transcriptional activity, measured by pTopFlash reporter, and induction of its
      target genes (CCND1 and c-MYC), as compared to control. Because of the role of
      AKT in regulating beta-catenin, we performed Western blot analysis and
      demonstrated that TFF1 reconstitution abrogates H. pylori-induced p-AKT (Ser473),
      p-beta-catenin (Ser552), c-MYC, and CCND1 protein levels. For in vivo validation,
      we utilized the Tff1-KO gastric neoplasm mouse model. Following infection with
      PMSS1 H. pylori strain, we detected an increase in the nuclear staining for beta
      catenin and Ki-67 with a significant induction in the levels of Ccnd1 and c-Myc
      in the stomach of the Tff1-KO, as compared to Tff1-WT mice (p < 0.05). Only 10%
      of uninfected Tff1-KO mice, as opposed to one-third of H. pylori-infected Tff1-KO
      mice, developed invasive adenocarcinoma (p = 0.03). These findings suggest that
      loss of TFF1 could be a critical step in promoting the H. pylori-mediated
      oncogenic activation of beta-catenin and gastric tumorigenesis.

PMID- 25980440
TI  - Genetic alterations of JAK/STAT cascade and histone modification in extranodal
      NK/T-cell lymphoma nasal type.
AB  - Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin
      lymphoma that more frequently occurs in East Asia and Latin America. Even though
      its molecular background has been discussed in the last few years, the current
      knowledge does not explain the disease pathogenesis in most cases of ENKL. Here,
      we performed multiple types of next-generation sequencing on 34 ENKL samples,
      including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines),
      targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and
      4 cancer cell lines). Mutations were found most frequently in 3 genes, STAT3,
      BCOR, and MLL2 (which were present in 9, 7, and 6 cancer samples, respectively),
      whereas there were only 2 cases of JAK3 mutation. In total, JAK/STAT pathway- and
      histone modification-related genes accounted for 55.9% and 38.2% of cancer
      samples, respectively, and their involvement in ENKL pathogenesis was also
      supported by gene expression analysis. In addition, we provided 177 genes
      upregulated only in cancer tissues, which appear to be linked with angiocentric
      and angiodestructive growth of ENKL. In this study, we propose several novel
      driver genes of ENKL, and show that these genes and their functional groups may
      be future therapeutic targets of this disease.

PMID- 25980441
TI  - XB130 translocation to microfilamentous structures mediates NNK-induced migration
      of human bronchial epithelial cells.
AB  - Cigarette smoking contributes to the pathogenesis of chronic obstructive
      pulmonary disease and lung cancer. Nicotine-derived nitrosamine ketone (NNK) is
      the most potent carcinogen among cigarette smoking components, and is known to
      enhance migration of cancer cells. However, the effect of NNK on normal human
      bronchial epithelial cells is not well studied. XB130 is a member of actin
      filament associated protein family and is involved in cell morphology changes,
      cytoskeletal rearrangement and outgrowth formation, as well as cell migration. We
      hypothesized that XB130 mediates NNK-induced migration of normal human bronchial
      epithelial cells. Our results showed that, after NNK stimulation, XB130 was
      translocated to the cell periphery and enriched in cell motility-associated
      structures, such as lamellipodia, in normal human bronchial epithelial BEAS2B
      cells. Moreover, overexpression of XB130 significantly enhanced NNK-induced
      migration, which requires both the N- and C-termini of XB130. Overexpression of
      XB130 enhanced NNK-induced protein tyrosine phosphorylation and promoted matrix
      metalloproteinase-14 translocation to cell motility-associated cellular
      structures after NNK stimulation. XB130-mediated NNK-induced cell migration may
      contribute to airway epithelial repair; however, it may also be involved in
      cigarette smoking-related chronic obstructive pulmonary disease and lung cancer.

PMID- 25980442
TI  - TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR
      373-3p expression to alter TGFbetaR2/p-Smad3 signals.
AB  - Testicular nuclear receptor 4 (TR4), a member of the nuclear receptor
      superfamily, may play important roles to modulate the metabolic diseases and
      prostate tumorigenesis. Here we found TR4 could increase prostate cancer (PCa)
      cell invasion. Mechanism dissection revealed that TR4 might increase PCa cell
      invasion via decreasing the miR-373-3p expression that resulted in the activation
      of the TGFbetaR2/p-Smad3 signals. The in vivo mouse model using orthotopically
      xenografted CWR22Rv1 cell line transfected with luciferase-reporter confirmed in
      vitro cell line studies showing TR4 increased PCa metastasis via decreasing the
      miR-373-3p expression. Together, these data suggest that TR4 may increase PCa
      metastasis via a newly identified signal and targeting these TR4/miR-473
      3p/TGFbetaR2/p-Smad3 signals using TR4 antagonist or TR4-siRNA or miR-373-3p may
      allow us to develop a new potential therapeutic approach to better suppress PCa
      metastasis. 

PMID- 25980443
TI  - Mitochondrial p53 phosphorylation induces Bak-mediated and caspase-independent
      cell death.
AB  - Chemoresistance in cancer has previously been attributed to gene mutations or
      deficiency. Caspase mutations or Bax deficiency can lead to resistance to cancer
      drugs. We recently demonstrated that Bak initiates a caspase/Bax-independent cell
      death pathway. We show that Plumbagin (PL) (5-hydroxy-2-methyl-1,4
      napthoquinone), a medicinal plant-derived naphthoquinone that is known to have
      anti-tumor activity in a variety of models, induces caspase-independent cell
      death in HCT116 Bax knockout (KO) or MCF-7 Bax knockdown (KD) cells that express
      wild-type (WT) Bak. The re-expression of Bax in HCT116 Bax KO cells fails to
      enhance the PL-induced cell death. Additionally, Bak knockdown by shRNA
      efficiently attenuates PL-induced cell death. These results suggest that PL
      induced cell death depends primarily on Bak, not Bax, in these cells. Further
      experimentation demonstrated that p53 Ser15 phosphorylation and mitochondrial
      translocation mediated Bak activation and subsequent cell death. Knockdown of p53
      or a p53 Ser15 mutant significantly inhibited p53 mitochondrial translocation and
      cell death. Furthermore, we found that Akt mediated p53 phosphorylation and the
      subsequent mitochondrial accumulation. Taken together, our data elaborate the
      role of Bak in caspase/Bax-independent cell death and suggest that PL may be an
      effective agent for overcoming chemoresistance in cancer cells with dysfunctional
      caspases. 

PMID- 25980444
TI  - Paroxysmal supraventricular tachycardia as first manifestation of right atrial
      hemangioma during endovascular treatment of intracranial arteriovenous fistulas.
AB  - We report the description of a cardiac mass occupying almost the entire right
      atrium in a young man who developed paroxysmal supraventricular tachycardia
      during endovascular treatment of intracranial arteriovenous fistulas. The mass
      was detected at echocardiographic examination, its tissue characteristics were
      defined with cardiac magnetic resonance and it was successfully surgically
      removed. The histopathological findings were consistent with a mixed type
      cavernous-capillary hemangioma of the heart. The intriguing co-existence of
      cardiac hemangioma and cerebral arteriovenous fistulas, to the best of our
      knowledge, has not been previously reported in English Literature. 

PMID- 25980445
TI  - Tethered bisadducts of C60 and C70 with addends on a common hexagonal face and a
      12-membered hole in the fullerene cage.
AB  - The regioselective synthesis of easily isolable pure bismethano derivatives of
      C60 and C70 with high steric congestion is described using 1,3-dibenzoylpropane
      bis-p-toluenesulfonyl hydrazone as the addend precursor. When the addition occurs
      at two [6,6] ring junctions within the same hexagon, bisadducts with mirror
      symmetry are obtained for both C60 and C70. When the addition occurs at two [5,6]
      ring junctions in C60, a symmetrical adduct is formed, which readily undergoes
      photo-oxygenation and ring opening to yield a fullerene with a hole in the cage.
      In this work, we also propose a simple and general system to name all of the
      possible [6,6] bisadduct isomers on C70. 

PMID- 25980448
TI  - A population-based study of the drug interaction between clopidogrel and
      angiotensin converting enzyme inhibitors.
AB  - AIMS: Clopidogrel and angiotensin converting enzyme (ACE) inhibitors are commonly
      co-prescribed drugs. Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme
      responsible for converting prodrug ACE inhibitors (such as ramipril and
      perindopril) to their active metabolites. The clinical implications of this
      potential drug interaction are unknown. The clinical consequences of the
      potential drug interaction between clopidogrel and prodrug ACE inhibitors were
      examined. METHODS: We conducted a nested case-control study of Ontarians aged 66
      years and older treated with clopidogrel between September 1 2003 and March 31
      2013 following acute myocardial infarction. Cases were subjects who died or were
      hospitalized for reinfarction or heart failure in the subsequent year, and each
      was matched with up to four controls. The primary outcome was a composite of
      reinfarction, heart failure or death. The primary analysis examined whether use
      of the prodrug ACE inhibitors ramipril or perindopril was more common among cases
      than use of lisinopril, an active ACE inhibitor. RESULTS: Among 45 918 patients
      treated with clopidogrel following myocardial infarction, we identified 4203
      cases and 14 964 controls. After adjustment, we found no association between the
      composite outcome and use of perindopril (adjusted odds ratio (aOR) 0.94, 95%
      confidence interval (CI) 0.76, 1.16) or ramipril (aOR 0.97, 95% CI 0.80, 1.18),
      relative to lisinopril. Secondary analyses of each element of the composite
      outcome yielded similar findings. CONCLUSIONS: Following myocardial infarction,
      use of clopidogrel with ACE inhibitors activated by CES1 is not associated with
      an increased risk of adverse cardiovascular outcomes relative to lisinopril.
      These findings suggest that the recently described drug interaction between
      clopidogrel and prodrug ACE inhibitors is of little clinical relevance.

PMID- 25980450
TI  - From the authors.

PMID- 25980449
TI  - Changes in secondary metabolic profiles of Microcystis aeruginosa strains in
      response to intraspecific interactions.
AB  - The cyanobacteria Microcystis proliferate in freshwater ecosystems and produce
      bioactive compounds including the harmful toxins microcystins (MC). These
      secondary metabolites play an important role in shaping community composition
      through biotic interactions although their role and mode of regulation are poorly
      understood. As natural cyanobacterial populations include producing and non
      producing strains, we tested if the production of a range of peptides by
      coexisting cells could be regulated through intraspecific interactions. With an
      innovative co-culturing chamber together with advanced mass spectrometry (MS)
      techniques, we monitored the growth and compared the metabolic profiles of a MC
      producing as well as two non-MC-producing Microcystis strains under mono- and co
      culture conditions. In monocultures, these strains grew comparably; however, the
      non-MC-producing mutant produced higher concentrations of cyanopeptolins,
      aerucyclamides and aeruginosins than the wild type. Physiological responses to co
      culturing were reflected in a quantitative change in the production of the major
      peptides. Using a MS/MS-based molecular networking approach, we identified new
      analogues of known classes of peptides as well as new compounds. This work
      provides new insights into the factors that regulate the production of MC and
      other secondary metabolites in cyanobacteria, and suggests interchangeable or
      complementary functions allowing bloom-forming cyanobacteria to efficiently
      colonize and dominate in fluctuating aquatic environments. 

PMID- 25980452
TI  - Understanding new "exploratory" biomarker data: a first look at observed
      concentrations and associated detection limits.

PMID- 25980453
TI  - New biomarkers for early detection of cardiotoxicity after treatment with
      docetaxel, doxorubicin and cyclophosphamide.
AB  - OBJECTIVE: Assessing a diverse biomarker panel (NT-proBNP, TNF-alpha, galectin-3,
      IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after
      treatment with anthracyclines. METHODS: Of 55 breast cancer patients biomarkers
      were assessed and echocardiography was performed one year after treatment with
      anthracyclines. RESULTS: 29.1% of patients showed abnormal biomarker levels: NT
      proBNP in 18.2%, TNF-alpha and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt
      1 were normal in all patients. A correlation between left ventricular ejection
      fraction (LVEF) and NT-proBNP was observed (r = -0.564, p <= 0.01). CONCLUSION:
      The evaluated biomarkers do not contribute to early detection. Future research
      should focus on NT-proBNP.

PMID- 25980455
TI  - Reply.

PMID- 25980454
TI  - Ruxolitinib for the treatment of patients with polycythemia vera.
AB  - Polycythemia vera (PV) is a hematopoietic proliferative disorder associated with
      Janus-associated kinase/signal transducer and activator of transcription pathway
      dysregulation resulting in erythrocytosis and, possibly, leukocytosis and
      thrombocytosis. Patients diagnosed with PV experience a broad range of symptoms
      associated with a reduced quality of life, often develop splenomegaly, and have
      an increased risk of death compared with age-matched subjects without PV. Current
      treatment options, notably hydroxyurea, help with disease management; however,
      insufficient efficacy or progressive resistance occurs in some patients,
      highlighting the need for new treatment options. Ruxolitinib is an oral JAK1/JAK2
      inhibitor that has been evaluated in Phase II and III clinical trials in patients
      with PV, who are intolerant of or resistant to hydroxyurea. In this setting,
      ruxolitinib treatment has demonstrated normalization of blood cell counts,
      reduction in splenomegaly and improvements in PV-related symptom burden. 

PMID- 25980456
TI  - Massive failure of TiNbN coating in surface engineered metal-on-metal hip
      arthroplasty: Retrieval analysis.
AB  - This article presents examination of a failed total hip replacement with surface
      engineered metal-on-metal (MoM) articulation. The implant was coated with a thin
      TiNbN film (Physical Vapor Deposition), and at retrieval 53 months after
      implantation the coating was abraded on weight-bearing part of the head and
      acetabular component. Scanning electron microscopy of bearing surfaces
      demonstrated multifocal crack formation, delamination of small film fragments,
      and formation of aggregates containing nanometer sized wear debris. We also
      observed coating damage in third body mechanism. Complex failure mechanism of
      TiNbN coating demonstrated in this study suggests insufficient bonding strength
      between the coating and substrate alloy and raise concerns regarding the use of
      such coatings in total hip arthroplasty with MoM bearing. (c) 2015 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1043-1049,
      2016.

PMID- 25980458
TI  - Telaprevir-induced moderate cutaneous eruptions associated with HHV-6
      reactivation.

PMID- 25980459
TI  - Ecosystem-scale volatile organic compound fluxes during an extreme drought in a
      broadleaf temperate forest of the Missouri Ozarks (central USA).
AB  - Considerable amounts and varieties of biogenic volatile organic compounds (BVOCs)
      are exchanged between vegetation and the surrounding air. These BVOCs play key
      ecological and atmospheric roles that must be adequately represented for
      accurately modeling the coupled biosphere-atmosphere-climate earth system. One
      key uncertainty in existing models is the response of BVOC fluxes to an important
      global change process: drought. We describe the diurnal and seasonal variation in
      isoprene, monoterpene, and methanol fluxes from a temperate forest ecosystem
      before, during, and after an extreme 2012 drought event in the Ozark region of
      the central USA. BVOC fluxes were dominated by isoprene, which attained high
      emission rates of up to 35.4 mg m(-2)  h(-1) at midday. Methanol fluxes were
      characterized by net deposition in the morning, changing to a net emission flux
      through the rest of the daylight hours. Net flux of CO2 reached its seasonal
      maximum approximately a month earlier than isoprenoid fluxes, which highlights
      the differential response of photosynthesis and isoprenoid emissions to
      progressing drought conditions. Nevertheless, both processes were strongly
      suppressed under extreme drought, although isoprene fluxes remained relatively
      high compared to reported fluxes from other ecosystems. Methanol exchange was
      less affected by drought throughout the season, confirming the complex processes
      driving biogenic methanol fluxes. The fraction of daytime (7-17 h) assimilated
      carbon released back to the atmosphere combining the three BVOCs measured was 2%
      of gross primary productivity (GPP) and 4.9% of net ecosystem exchange (NEE) on
      average for our whole measurement campaign, while exceeding 5% of GPP and 10% of
      NEE just before the strongest drought phase. The meganv2.1 model correctly
      predicted diurnal variations in fluxes driven mainly by light and temperature,
      although further research is needed to address model BVOC fluxes during drought
      events. 

PMID- 25980457
TI  - Contribution of estrogen receptor subtypes, ERalpha, ERbeta, and GPER1 in rapid
      estradiol-mediated enhancement of hippocampal synaptic transmission in mice.
AB  - Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic
      transmission; however, the contribution of the various estrogen receptors to
      rapid changes in synaptic function is unclear. This study examined the effect of
      estrogen receptor selective agonists on hippocampal synaptic transmission in
      slices obtained from 3-5-month-old wild type (WT), estrogen receptor alpha
      (ERalphaKO), and beta (ERbetaKO) knockout female ovariectomized mice. Hippocampal
      slices were prepared 10-16 days following ovariectomy and extracellular
      excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic
      contacts before and following application of 17beta-estradiol-3-benzoate (EB, 100
      pM), the G-protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ERalpha
      selective agonist propyl pyrazole triol (PPT, 100 nM), or the ERbeta selective
      agonist diarylpropionitrile (DPN, 1 uM). Across all groups, EB and G1 increased
      the synaptic response to a similar extent. Furthermore, prior G1 application
      occluded the EB-mediated enhancement of the synaptic response and the GPER1
      antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response
      induced by EB application. We confirmed that the ERalpha and ERbeta selective
      agonists (PPT and DPN) had effects on synaptic responses specific to animals that
      expressed the relevant receptor; however, PPT and DPN produced only a small
      increase in synaptic transmission relative to EB or the GPER1 agonist. We
      demonstrate that the increase in synaptic transmission is blocked by inhibition
      of extracellular signal-regulated kinase (ERK) activity. Furthermore, EB was able
      to increase ERK activity regardless of genotype. These results suggest that ERK
      activation and enhancement of synaptic transmission by EB involves multiple
      estrogen receptor subtypes.

PMID- 25980460
TI  - Bioinformatics approach for choosing the correct reference genes when studying
      gene expression in human keratinocytes.
AB  - Reverse transcription polymerase chain reaction (qRT-PCR) has become a mainstay
      in many areas of skin research. To enable quantitative analysis, it is necessary
      to analyse expression of reference genes (RGs) for normalization of target gene
      expression. The selection of reliable RGs therefore has an important impact on
      the experimental outcome. In this study, we aimed to identify and validate the
      best suited RGs for qRT-PCR in human primary keratinocytes (KCs) over a broad
      range of experimental conditions using the novel bioinformatics tool 'RefGenes',
      which is based on a manually curated database of published microarray data.
      Expression of 6 RGs identified by RefGenes software and 12 commonly used RGs were
      validated by qRT-PCR. We assessed whether these 18 markers fulfilled the
      requirements for a valid RG by the comprehensive ranking of four bioinformatics
      tools and the coefficient of variation (CV). In an overall ranking, we found GUSB
      to be the most stably expressed RG, whereas the expression values of the commonly
      used RGs, GAPDH and B2M were significantly affected by varying experimental
      conditions. Our results identify RefGenes as a powerful tool for the
      identification of valid RGs and suggest GUSB as the most reliable RG for KCs. 

PMID- 25980461
TI  - Prognostic characteristics of duodenal gastrointestinal stromal tumours.
AB  - BACKGROUND: This study evaluated the clinical characteristics, surgical
      procedures and prognosis of duodenal gastrointestinal stromal tumours (GISTs).
      METHODS: Patients with a diagnosis of primary duodenal GIST treated between
      January 2000 and December 2012 were analysed. Patients with gastric and small
      intestinal GISTs were chosen as control groups according to the following
      parameters: age, tumour size, mitotic index and adjuvant imatinib therapy.
      Operative procedures for patients with duodenal GIST included
      pancreaticoduodenectomy or limited resection. Disease-free survival (DFS) was
      calculated using Kaplan-Meier analysis. RESULTS: Some 71 patients with duodenal,
      71 with gastric and 70 with small intestinal GISTs were included in the study.
      DFS of patients with duodenal GIST was shorter than that of patients with gastric
      GIST (3-year DFS 84 versus 94 per cent; hazard ratio (HR) 3.67, 95 per cent c.i.
      1.21 to 11.16; P = 0.014), but was similar to that of patients with small
      intestinal GIST (3-year DFS 84 versus 81 per cent; HR 0.75, 0.37 to 1.51; P =
      0.491). Patients who underwent pancreaticoduodenectomy were older, and had larger
      tumours and a higher mitotic index than patients who had limited resection. The 3
      year DFS was 93 per cent among patients who had limited resection compared with
      64 per cent for those who underwent PD (HR 0.18, 0.06 to 0.59; P = 0.001).
      CONCLUSION: The prognosis of duodenal GISTs is similar to that of small
      intestinal GISTs.

PMID- 25980462
TI  - Velocity measurement of microvessels using phase-contrast magnetic resonance
      angiography at 7 Tesla MRI.
AB  - PURPOSE: The purpose of this study was to measure the velocity and direction of
      blood flow in microvessels, such as lenticulostriate arteries (LSAs), using PC
      MRA. METHODS: Eleven healthy subjects were scanned with 7 Tesla (T) MRI. Three
      velocity encoding (VENC) values of 15, 50, and 100 cm/s were tested for detecting
      the flow velocity in LSAs. The flow directions in Circle of Willis (CoW) were
      also examined with images obtained by the proposed method. Three subjects were
      also scanned with 3T MRI to determine the possibility of velocity measurement in
      LSAs. Difference between 3T and 7T was quantitatively analyzed in terms of signal
      to-noise ratio and velocities in vessels and static tissues. RESULTS: In 7T MRI,
      use of VENC = 15 cm/s provided great visualization and velocity measurements in
      small and slow flowing vessels, such as the LSAs. The mean of peak velocities in
      LSAs was 9.61 +/- 1.78 cm/s. The results obtained with low VENC also clearly
      depicted the directions of flow in CoW, especially in posterior communicating
      arteries. However, 3T MRI could not detect the velocity of blood flow in LSAs.
      CONCLUSION: This study demonstrated the potential for measuring the velocity and
      direction of blood flow in the targeted microvessels using an appropriate VENC
      and 7T MRI.

PMID- 25980463
TI  - A Hoxa13:Cre mouse strain for conditional gene manipulation in developing limb,
      hindgut, and urogenital system.
AB  - The developing limb is a useful model for studying organogenesis and
      developmental processes. Although Cre alleles exist for conditional loss- or gain
      of-function in limbs, Cre alleles targeting specific limb subdomains are
      desirable. Here we report on the generation of the Hoxa13:Cre line, in which the
      Cre gene is inserted in the endogenous Hoxa13 gene. We provide evidence that the
      Cre is active in embryonic tissues/regions where the endogenous Hoxa13 gene is
      expressed. Our results show that cells expressing Hoxa13 in developing limb buds
      contribute to the entire autopod (hand/feet) skeleton and validate Hoxa13 as a
      distal limb marker as far as the skeleton is concerned. In contrast, in the limb
      musculature, Cre-based fate mapping shows that almost all muscle masses of the
      zeugopod (forearm) and part of the triceps contain Hoxa13-expressing cells and/or
      their descendants. Besides the limb, the activity of the Cre is detectable in the
      urogenital system and the hindgut, primarily in the epithelium and smooth
      muscles. Together our data show that the Hoxa13:Cre allele is a useful tool for
      conditional gene manipulation in the urogenital system, posterior digestive
      tract, autopod and part of the limb musculature.

PMID- 25980464
TI  - In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate
      Buffer on the Dissolution of Weak Acids and Weak Bases.
AB  - Bicarbonate is the main buffer in the small intestine and it is well known that
      buffer properties such as pKa can affect the dissolution rate of ionizable drugs.
      However, bicarbonate buffer is complicated to work with experimentally. Finding a
      suitable substitute for bicarbonate buffer may provide a way to perform more
      physiologically relevant dissolution tests. The dissolution of weak acid and weak
      base drugs was conducted in bicarbonate and phosphate buffer using rotating disk
      dissolution methodology. Experimental results were compared with the predicted
      results using the film model approach of (Mooney K, Mintun M, Himmelstein K,
      Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well
      as a model accounting for the slow hydration reaction, CO2 + H2 O -> H2 CO3 .
      Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O <
      H2 CO3 , the transport analysis can accurately predict rotating disk dissolution
      of weak acid and weak base drugs in bicarbonate buffer. The predictions show that
      matching the dissolution of weak acid and weak base drugs in phosphate and
      bicarbonate buffer is possible. The phosphate buffer concentration necessary to
      match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH
      = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug
      solubility and pKa .

PMID- 25980465
TI  - A Combined Transition-Metal-Catalyzed and Photopromoted Process: Synthesis of 2,3
      Fused 4-Phenylnaphthalen-1-yl Carboxylates from 1,7-Diaryl-1,6-diynes.
AB  - 2,3-Fused 4-phenylnaphthalen-1-yl carboxylates were synthesized in a step- and
      atom-economical manner using a ruthenium-catalyzed hydrocarboxylative cyclization
      of 1,7-diaryl-1,6-diynes and subsequent oxidative photocyclization. The scope of
      this novel two-step process was demonstrated by the construction of diverse
      structures from substrates with various tethers and terminal aryl groups. Late
      stage C?H functionalizations of the arylnaphthalene product further enhance the
      synthetic potential of the developed process. 

PMID- 25980466
TI  - A durable surface-enhanced Raman scattering substrate: ultrathin carbon layer
      encapsulated Ag nanoparticle arrays on indium-tin-oxide glass.
AB  - The application of Ag nanostructures to surface-enhanced Raman scattering (SERS)
      is hindered by their chemical instability. Fabrication of durable Ag-based SERS
      substrates is therefore of great significance in practical applications. In this
      work, ultrathin C-layer-encapsulated Ag nanoparticle arrays (UCL-Ag-NAs) are
      successfully fabricated on the surface of indium-tin-oxide (ITO) glass, using a
      hydrothermal method, for use as durable SERS substrates. The problem of Ag
      nanoparticles dissolving during the hydrothermal process is solved by using ZnO
      powder as a pH-buffering reagent. The SERS signal intensity of UCL-Ag-NAs
      decreases, accompanied by an improvement in Raman signal stability, as the C
      layer thickness increases. Raman spectra show that the SERS signal intensities
      obtained from UCL-Ag-NAs with C-layers of 4.5 nm and 7.3 nm stored for 180 days
      are 64.9% and 77.8% of those obtained from as-prepared counterparts. The SERS
      intensity of the UCL-Ag-NA (C-layer of 4.5 nm) is 152.7% that of the bare Ag NA
      after 180 days of storage. XPS spectra confirm that the C-layer effectively
      suppresses the oxidation of the Ag NA. This methodology can be generalized to
      improve the durability of other dimensional Ag nanostructures for SERS
      applications. 

PMID- 25980467
TI  - Basal metabolic rate in children with chronic kidney disease and healthy control
      children.
AB  - BACKGROUND: Meeting energy requirements of children with chronic kidney disease
      (CKD) is paramount to optimising growth and clinical outcome, but little
      information on this subject has been published. In this study, we examined basal
      metabolic rate (BMR; a component of energy expenditure) with the aim to determine
      whether it is related to kidney function independently of weight, height and lean
      body mass (LBM). METHODS: Twenty children with CKD and 20 healthy age- and gender
      matched control children were studied on one occasion. BMR was measured by
      indirect open circuit calorimetry and predicted by the Schofield equation.
      Estimated glomerular filtration rate (eGFR) was related to BMR and adjusted for
      weight, height, age and LBM measured by skinfold thickness. RESULTS: The adjusted
      BMR of children with CKD did not differ significantly from that of healthy
      subjects (1296 +/- 318 vs.1325 +/- 178 kcal/day; p = 0.720). Percentage of
      predicted BMR also did not differ between the two groups (102 +/- 12% vs. 99 +/-
      14%; p = 0.570). Within the CKD group, eGFR (mean 33.7 +/- 20.5 mL/min/m(2)) was
      significantly related to BMR (beta 0.3, r = 0.517, p = 0.019) independently of
      nutritional status and LBM. CONCLUSIONS: It seems reasonable to use estimated
      average requirement as the basis of energy prescriptions for children with CKD
      (mean CKD stage 3 disease). However, those who were sicker had significantly
      lower metabolic rates.

PMID- 25980468
TI  - The effect of vitamin A on renal damage following acute pyelonephritis in
      children: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Renal scarring after acute pyelonephritis (APN) in children is of
      concern and in the worst cases leads to long-term cardiovascular morbidity. There
      are reports that vitamin A may alleviate renal damage following APN. We conducted
      a meta-analysis to investigate the role of vitamin A in the alleviation of renal
      damage. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of
      Controlled trials (CENTRAL, the Cochrane Library) and the Wang Fang database
      (Chinese) from their inception to February 3, 2015 for randomized controlled
      trials (RCTs) investigating vitamin A and renal damage. Primary outcome was
      number of patients/kidneys with renal damage, defined as persistence of
      photopenic lesions based on technetium-99m dimercaptosuccinic acid renal
      scintigraphy. We calculated pooled relative risks for renal damage in the vitamin
      A group. RESULTS: Four RCTs, involving a total of 248 patients aged 1-144 months
      (120 in experimental group, 128 in control group), were included in the meta
      analysis. Vitamin A was inversely associated with renal damage (relative risk
      0.53, 95 % confidence interval 0.43, 0.67) when compared with placebo group after
      an average follow-up of 5 months. CONCLUSIONS: Current evidence indicates that
      vitamin A may exert a preventive effect on renal damage in children with APN.
      However, this finding largely relies on a few studies of low methodological
      quality, i.e., high risk of selection bias, performance bias and attrition bias.
      Hence, high-quality and adequately powered RCTs are warranted.

PMID- 25980469
TI  - Biomarkers and surrogate endpoints in kidney disease.
AB  - Kidney disease and its related comorbidities impose a large public health burden.
      Despite this, the number of clinical trials in nephrology lags behind many other
      fields. An important factor contributing to the relatively slow pace of
      nephrology trials is that existing clinical endpoints have significant
      limitations. "Hard" endpoints for chronic kidney disease, such as progression to
      end-stage renal disease, may not be reached for decades. Traditional biomarkers,
      such as serum creatinine in acute kidney injury, may lack sensitivity and
      predictive value. Finding new biomarkers to serve as surrogate endpoints is
      therefore an important priority in kidney disease research and may help to
      accelerate nephrology clinical trials. In this paper, I first review key concepts
      related to the selection of clinical trial endpoints and discuss statistical and
      regulatory considerations related to the evaluation of biomarkers as surrogate
      endpoints. This is followed by a discussion of the challenges and opportunities
      in developing novel biomarkers and surrogate endpoints in three major areas of
      nephrology research: acute kidney injury, chronic kidney disease, and autosomal
      dominant polycystic kidney disease. 

PMID- 25980472
TI  - Tentative Structural Assignment of a Glucuronide Metabolite of Methyltestosterone
      in Tilapia Bile by Liquid Chromatography-Quadrupole-Time-of-Flight Mass
      Spectrometry.
AB  - Methyltestosterone (MT), a strong androgenic steroid, is not approved for use in
      fish aquaculture in the United States. It is used in the U.S. under an
      investigational new animal drug exemption (INAD) only during the early life
      stages of fish. There is a possibility that farmers feed fish with MT to enhance
      production for economic gains. Therefore, there is a need to develop methods for
      the detection of MT and its metabolite residues in fish tissue for monitoring
      purposes. Previously, our laboratory developed a liquid chromatography-quadrupole
      time-of-flight (LC-QTOF) method for characterization of 17-O-glucuronide
      metabolite (MT-glu) in bile of tilapia dosed with MT. The system used was an
      Agilent 6530 Q-TOF equipped with electrospray jet stream technology, operating in
      positive ion mode. Retrospective analysis of the data generated in that
      experiment by a feature-finding algorithm, combined with a search against an in
      house library of possible MT-metabolites, resulted in the discovery of a major
      glucuronide metabolite of MT in the bile extracts. Preliminary data indicate it
      to be a glucuronide of a hydroxylated MT (OHMT-glu) which persists in tilapia
      bile for at least 2 weeks after dosing. We present the tentative structural
      assignment of the OHMT-glu in tilapia bile and time course of development. This
      glucuronide can serve as a marker to monitor illegal use of MT in tilapia
      culture. 

PMID- 25980470
TI  - Haematuria as a risk factor for chronic kidney disease progression in glomerular
      diseases: A review.
AB  - Haematuria has long been considered to be a benign condition associated with
      glomerular diseases. However, new evidences suggest that haematuria has a
      pathogenic role in promoting kidney disease progression. An increased risk for
      end-stage renal disease has been reported in adolescents and young adults with
      persistent microscopic haematuria. A persistent impairment of renal function has
      been also reported following macroscopic haematuria-associated acute kidney
      injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been
      related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or
      haem released from red blood cells. The pathophysiological origin of haematuria
      may be due to a more fragile and easily ruptured glomerular filtration barrier,
      as reported in several glomerular diseases. In this review we describe a number
      of the key issues associated with the epidemiology and pathogenesis of haematuria
      associated diseases, provide an update of recent knowledge on the role of
      haematuria on renal function outcome and discuss specific therapeutic approaches
      in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common
      observation in a number of renal diseases that may lead to persistent renal
      injury. 2. Haematuria in children differs from that in adults in specific
      aspects, particularly in the frequency of glomerular diseases and renal disease
      outcome. 3. Regular follow-up of renal function in children with isolated
      microhaematuria may be recommended.

PMID- 25980471
TI  - Renal functional and structural integrity in infants with iron deficiency anemia:
      relation to oxidative stress and response to iron therapy.
AB  - BACKGROUND: Iron deficiency anemia (IDA) is the most common nutritional
      deficiency in the world. The aim of our study was to evaluate and compare renal
      functional and structural integrity in 50 infants with IDA and 50 healthy
      controls and to assess the relation between IDA and oxidative stress and response
      to iron therapy. METHODS: This was a prospective study in which peripheral blood
      samples were collected from all study subjects and the following laboratory
      investigations performed: serum iron profile, urinary microalbumin, urinary
      leucine aminopeptidase (LAP), fractional excretion of sodium (FeNa), serum total
      antioxidant capacity (TAC), serum malondialdehyde (MDA), serum and urinary trace
      elements (iron, copper, zinc, calcium and magnesium). All patients received oral
      iron therapy and were followed-up for 3 months. RESULTS: The levels of baseline
      urinary markers were higher among the patients with IDA than among the controls
      (p < 0.05). Patients had a lower pre-therapy TAC and lower serum zinc and
      magnesium levels than controls as well as higher MDA and serum copper levels (p <
      0.05). MDA level was positively correlated to microalbumin and LAP level (p <
      0.05). Urinary LAP concentration was positively correlated to urinary trace
      element concentrations (p < 0.05). A significant decrease in microalbumin, LAP,
      FeNa, and urinary trace elements was observed post-iron therapy while hemoglobin
      and ferritin levels were increased (p < 0.05). CONCLUSION: Among the study
      subjects, IDA had an adverse influence on renal functional and structural
      integrity which could be reversed with iron therapy. Oxidative stress played an
      important role in the pathogenesis of renal injury in IDA.

PMID- 25980473
TI  - The Advantages of an Attenuated Total Internal Reflection Infrared
      Microspectroscopic Imaging Technique for the Analysis of Polymer Laminates.
AB  - Until recently, the analysis of polymer laminates using infrared
      microspectroscopy involved the painstaking separation of individual layers by
      dissection or by obtaining micrometer thin cross-sections. The latter usually
      requires the expertise of an individual trained in microtomy and even then, the
      very structure of the laminate could affect the outcome of the spectral results.
      The recent development of attenuated total internal reflection (ATR) infrared
      microspectroscopy imaging has provided a new avenue for the analysis of these
      multilayer structures. This report compares ATR infrared microspectroscopy
      imaging with conventional transmission infrared microspectroscopy imaging. The
      results demonstrate that the ATR method offers improved spatial resolution,
      eliminates a variety of competing optical processes, and requires minimal sample
      preparation relative to transmission measurements. These advantages were
      illustrated using a polymer laminate consisting of 11 different layers whose
      thickness ranged in size from 4-20 MUm. The spatial resolution achieved by using
      an ATR-FTIR (Fourier transform infrared spectroscopy) imaging technique was
      diffraction limited. Contrast in the ATR images was enhanced by principal
      component analysis. 

PMID- 25980474
TI  - Enhanced astroglial Ca2+ signaling increases excitatory synaptic strength in the
      epileptic brain.
AB  - The fine-tuning of synaptic transmission by astrocyte signaling is crucial to CNS
      physiology. However, how exactly astroglial excitability and gliotransmission are
      affected in several neuropathologies, including epilepsy, remains unclear. Here,
      using a chronic model of temporal lobe epilepsy (TLE) in rats, we found that
      astrocytes from astrogliotic hippocampal slices displayed an augmented incidence
      of TTX-insensitive spontaneous slow Ca(2+) transients (STs), suggesting a
      hyperexcitable pattern of astroglial activity. As a consequence, elevated
      glutamate-mediated gliotransmission, observed as increased slow inward current
      (SICs) frequency, up-regulates the probability of neurotransmitter release in CA3
      CA1 synapses. Selective blockade of spontaneous astroglial Ca(2+) elevations as
      well as the inhibition of purinergic P2Y1 or mGluR5 receptors relieves the
      abnormal enhancement of synaptic strength. Moreover, mGluR5 blockade eliminates
      any synaptic effects induced by P2Y1R inhibition alone, suggesting that the Pr
      modulation via mGluR occurs downstream of P2Y1R-mediated Ca(2+)-dependent
      glutamate release from astrocyte. Our findings show that elevated Ca(2+)
      dependent glutamate gliotransmission from hyperexcitable astrocytes up-regulates
      excitatory neurotransmission in epileptic hippocampus, suggesting that
      gliotransmission should be considered as a novel functional key in a broad
      spectrum of neuropathological conditions.

PMID- 25980476
TI  - Reversible phenotypic plasticity with continuous adaptation.
AB  - We introduce a novel model for continuous reversible phenotypic plasticity. The
      model includes a one-dimensional environmental gradient, and we describe
      performance of an organism as a function of the environmental state by a Gaussian
      tolerance curve. Organisms are assumed to adapt their tolerance curve after a
      change of the environmental state. We present a general framework for calculating
      the genotype fitness if such adaptations happen in a continuous manner and apply
      the model to a periodically changing environment. Significant differences of our
      model with previous models for plasticity are the continuity of adaptation, the
      presence of intermediate phenotypes, that the duration of transformations depends
      on their extent, fewer restrictions on the distribution of the environment, and a
      higher robustness with respect to assumptions about environmental fluctuations.
      Further, we show that continuous reversible plasticity is beneficial mainly when
      environmental changes occur slow enough so that fully developed phenotypes can be
      exhibited. Finally we discuss how the model framework can be generalized to a
      wide variety of biological scenarios from areas that include population dynamics,
      evolution of environmental tolerance and physiology. 

PMID- 25980475
TI  - MicroRNA-23b Promotes Avian Leukosis Virus Subgroup J (ALV-J) Replication by
      Targeting IRF1.
AB  - Avian leukosis virus subgroup J (ALV-J) can cause several different leukemia-like
      proliferative diseases in the hemopoietic system of chickens. Here, we
      investigated the transcriptome profiles and miRNA expression profiles of ALV-J
      infected and uninfected chicken spleens to identify the genes and miRNAs related
      to ALV-J invasion. In total, 252 genes and 167 miRNAs were differentially
      expressed in ALV-J-infected spleens compared to control uninfected spleens. miR
      23b expression was up-regulated in ALV-J-infected spleens compared with the
      control spleens, and transcriptome analysis revealed that the expression of
      interferon regulatory factor 1 (IRF1) was down-regulated in ALV-J-infected
      spleens compared to uninfected spleens. A dual-luciferase reporter assay showed
      that IRF1 was a direct target of miR-23b. miR-23b overexpression significantly (P
      = 0.0022) decreased IRF1 mRNA levels and repressed IRF1-3'-UTR reporter activity.
      In vitro experiments revealed that miR-23b overexpression strengthened ALV-J
      replication, whereas miR-23b loss of function inhibited ALV-J replication. IRF1
      overexpression inhibited ALV-J replication, and IRF1 knockdown enhanced ALV-J
      replication. Moreover, IRF1 overexpression significantly (P = 0.0014) increased
      IFN-beta expression. In conclusion, these results suggested that miR-23b may play
      an important role in ALV-J replication by targeting IRF1.

PMID- 25980477
TI  - Mathematical Analysis of the Effects of HIV-Malaria Co-infection on Workplace
      Productivity.
AB  - In this paper, a nonlinear dynamical system is proposed and qualitatively
      analyzed to study the dynamics and effects of HIV-malaria co-infection in the
      workplace. Basic reproduction numbers of sub-models are derived and are shown to
      have LAS disease-free equilibria when their respective basic reproduction numbers
      are less than unity. Conditions for existence of endemic equilibria of sub-models
      are also derived. Unlike the HIV-only model, the malaria-only model is shown to
      exhibit a backward bifurcation under certain conditions. Conditions for optimal
      control of the co-infection are derived using the Pontryagin's maximum principle.
      Numerical experimentation on the resulting optimality system is performed. Using
      the incremental cost-effectiveness ratio, it is observed that combining
      preventative measures for both diseases is the best strategy for optimal control
      of HIV-malaria co-infection at the workplace. 

PMID- 25980478
TI  - A solution to the biodiversity paradox by logical deterministic cellular
      automata.
AB  - The paradox of biological diversity is the key problem of theoretical ecology.
      The paradox consists in the contradiction between the competitive exclusion
      principle and the observed biodiversity. The principle is important as the basis
      for ecological theory. On a relatively simple model we show a mechanism of
      indefinite coexistence of complete competitors which violates the known
      formulations of the competitive exclusion principle. This mechanism is based on
      timely recovery of limiting resources and their spatio-temporal allocation
      between competitors. Because of limitations of the black-box modeling there was a
      problem to formulate the exclusion principle correctly. Our white-box multiscale
      model of two-species competition is based on logical deterministic individual
      based cellular automata. This approach provides an automatic deductive inference
      on the basis of a system of axioms, and gives a direct insight into mechanisms of
      the studied system. It is one of the most promising methods of artificial
      intelligence. We reformulate and generalize the competitive exclusion principle
      and explain why this formulation provides a solution of the biodiversity paradox.
      In addition, we propose a principle of competitive coexistence. 

PMID- 25980479
TI  - It is the flash which appears, the movement will follow: Investigating the
      relation between spatial attention and obstacle avoidance.
AB  - Obstacles are represented in the attentional landscape. However, it is currently
      unclear what the exclusive contribution of attention is to the avoidance
      response. This is because in earlier obstacle avoidance designs, it was
      impossible to disentangle an effect of attention from the changing features of
      the obstacle (e.g., its identity, size, or orientation). Conversely, any feature
      manipulation could be interpreted as an attentional as well as an obstacle effect
      on avoidance behavior. We tested the possible tuning of avoidance responses by a
      spatial cue in two experiments. In both experiments, spatial and nonspatial cues
      were separately given as go cues for an obstacle avoidance task. Participants had
      to reach past two obstacles in Experiment 1, and past a single obstacle in
      Experiment 2. We found that when the right obstacle was flashed, participants
      veered away more and produced more-variable trajectories over trials than in
      conditions with nonspatial and left spatial cues, regardless of the presence or
      absence of another obstacle. Therefore, we concluded that the tuning of avoidance
      responses can be influenced by spatial cues. Moreover, we speculated that a
      flashed obstacle receives more attentional weighting in the attentional landscape
      and prompts a stronger repulsion away from the obstacle. 

PMID- 25980480
TI  - Digital radiographs displayed on different devices: effect on the detection of
      vertical root fractures.
AB  - AIM: To evaluate whether the type of display device affects the detection of
      vertical root fractures (VRFs) on digital radiographs in unfilled canals and
      canals with fibreglass posts. METHODOLOGY: Forty single-rooted human teeth were
      decoronated, and the root canals were prepared. The teeth were divided into 2
      groups: controls (20 teeth) and with VRF (20 teeth). The VRFs were induced using
      an universal testing machine. Periapical radiographs of all teeth, with canal
      unfilled or with a fibreglass post, were obtained using the parallel technique in
      3 directions (ortho-, mesio- and distoradial) on storage phosphor plates
      (VistaScan(r)). All images were evaluated and re-evaluated after 30 days by 3
      examiners on a 5-point scale using 4 different devices (notebook display with
      full high definition resolution, desktop display with a standard resolution, 8
      inch Android(TM) tablet with high definition resolution and a 9.7-inch iPad(r)
      tablet with Retina resolution). Areas under ROC curves, sensitivity, specificity
      and accuracy values were compared by anova. RESULTS: The weighted kappa values
      for intra- and interobserver reproducibility were 0.55-0.88 and 0.31-0.65,
      respectively. There was a significant difference (P < 0.05) in relation to the
      area under the ROC curve, specificity and sensitivity when unfilled canals were
      compared with canals with a fibreglass post; however, no difference was observed
      for the different devices studied. CONCLUSIONS: The type of display device did
      not affect the detection of VRFs. Thus, the detection of VRFs can be performed
      using different screen sizes and resolutions.

PMID- 25980481
TI  - The first clinical application of planning software for laparoscopic microwave
      thermosphere ablation of malignant liver tumours.
AB  - BACKGROUND: Liver tumour ablation is an operator-dependent procedure. The
      determination of the optimum needle trajectory and correct ablation parameters
      could be challenging. The aim of this study was to report the utility of a new,
      procedure planning software for microwave ablation (MWA) of liver tumours.
      METHODS: This was a feasibility study in a pilot group of five patients with nine
      metastatic liver tumours who underwent laparoscopic MWA. Pre-operatively,
      parameters predicting the desired ablation zones were calculated for each tumour.
      Intra-operatively, this planning strategy was followed for both antenna placement
      and energy application. Post-operative 2-week computed tomography (CT) scans were
      performed to evaluate complete tumour destruction. RESULTS: The patients had an
      average of two tumours (range 1-4), measuring 1.9 +/- 0.4 cm (range 0.9-4.4 cm).
      The ablation time was 7.1 +/- 1.3 min (range 2.5-10 min) at 100W. There were no
      complications or mortality. The patients were discharged home on post-operative
      day (POD) 1. At 2-week CT scans, there were no residual tumours, with a complete
      ablation demonstrated in all lesions. CONCLUSIONS: This study describes and
      validates pre-treatment planning software for MWA of liver tumours. This software
      was found useful to determine precisely the ablation parameters and needle
      placement to create a predicted zone of ablation.

PMID- 25980482
TI  - Ketamine induces a robust whole-brain connectivity pattern that can be
      differentially modulated by drugs of different mechanism and clinical profile.
AB  - Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied
      in relation to the glutamate hypothesis of schizophrenia and increases
      dissociation, positive and negative symptom ratings. Ketamine effects brain
      function through changes in brain activity; these activity patterns can be
      modulated by pre-treatment of compounds known to attenuate the effects of
      ketamine on glutamate release. Ketamine also has marked effects on brain
      connectivity; we predicted that these changes would also be modulated by
      compounds known to attenuate glutamate release. Here, we perform task-free
      pharmacological magnetic resonance imaging (phMRI) to investigate the functional
      connectivity effects of ketamine in the brain and the potential modulation of
      these effects by pre-treatment of the compounds lamotrigine and risperidone,
      compounds hypothesised to differentially modulate glutamate release. Connectivity
      patterns were assessed by combining windowing, graph theory and multivariate
      Gaussian process classification. We demonstrate that ketamine has a robust effect
      on the functional connectivity of the human brain compared to saline (87.5 %
      accuracy). Ketamine produced a shift from a cortically centred, to a
      subcortically centred pattern of connections. This effect is strongly modulated
      by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based
      on the differential effect of these compounds on ketamine response, we suggest
      the observed connectivity effects are primarily due to NMDAR blockade rather than
      downstream glutamatergic effects. The connectivity changes contrast with
      amplitude of response for which no differential effect between pre-treatments was
      detected, highlighting the necessity of these techniques in forming an informed
      view of the mechanistic effects of pharmacological compounds in the human brain. 

PMID- 25980483
TI  - Common and distinct neural effects of risperidone and olanzapine during
      procedural learning in schizophrenia: a randomised longitudinal fMRI study.
AB  - RATIONALE: Most cognitive domains show only minimal improvement following typical
      or atypical antipsychotic treatments in schizophrenia, and some may even worsen.
      One domain that may worsen is procedural learning, an implicit memory function
      relying mainly on the integrity of the fronto-striatal system. OBJECTIVES: We
      investigated whether switching to atypical antipsychotics would improve
      procedural learning and task-related neural activation in patients on typical
      antipsychotics. Furthermore, we explored the differential effects of the atypical
      antipsychotics risperidone and olanzapine. METHODS: Thirty schizophrenia patients
      underwent functional magnetic resonance imaging during a 5-min procedural
      (sequence) learning task on two occasions: at baseline and 7-8 weeks later. Of 30
      patients, 10 remained on typical antipsychotics, and 20 were switched randomly in
      equal numbers to receive either olanzapine (10-20 mg) or risperidone (4-8 mg) for
      7-8 weeks. RESULTS: At baseline, patients (all on typical antipsychotics) showed
      no procedural learning. At follow-up, patients who remained on typical
      antipsychotics continued to show a lack of procedural learning, whereas those
      switched to atypical antipsychotics displayed significant procedural learning (p
      = 0.001) and increased activation in the superior-middle frontal gyrus, anterior
      cingulate and striatum (cluster-corrected p < 0.05). These neural effects were
      present as a linear increase over five successive 30-s blocks of sequenced
      trials. A switch to either risperidone or olanzapine resulted in comparable
      performance but with both overlapping and distinct task-related activations.
      CONCLUSIONS: Atypical antipsychotics restore procedural learning deficits and
      associated neural activity in schizophrenia. Furthermore, different atypical
      antipsychotics produce idiosyncratic task-related neural activations, and this
      specificity may contribute to their differential long-term clinical profiles.

PMID- 25980484
TI  - Serotonin transporter occupancy by escitalopram and citalopram in the non-human
      primate brain: a [(11)C]MADAM PET study.
AB  - RATIONALE: A number of serotonin receptor positron emission tomography (PET)
      radioligands have been shown to be sensitive to changes in extracellular
      serotonin concentration, in a generalization of the well-known dopamine
      competition model. High doses of selective serotonin reuptake inhibitors (SSRIs)
      decrease serotonin receptor availability in monkey brain, consistent with
      increased serotonin concentrations. However, two recent studies on healthy human
      subjects, using a single, lower and clinically relevant SSRI dose, showed
      increased cortical serotonin receptor radioligand binding, suggesting potential
      decreases in serotonin concentration in projection regions when initiating
      treatment. OBJECTIVES: The cross-species differential SSRI effect may be partly
      explained by serotonin transporter (SERT) occupancy in monkey brain being higher
      than is clinically relevant. We here determine SERT occupancy after single doses
      of escitalopram or citalopram by conducting PET measurements with [(11)C]MADAM in
      monkeys. Relationships between dose, plasma concentration and SERT occupancy were
      estimated by one-site binding analyses. Binding affinity was expressed as dose
      (ID50) or plasma concentration (K i) where 50 % SERT occupancy was achieved.
      RESULTS: Estimated ID50 and K i values were 0.020 mg/kg and 9.6 nmol/L for
      escitalopram and 0.059 mg/kg and 9.7 nmol/L for citalopram, respectively.
      Obtained K i values are comparable to values reported in humans. CONCLUSIONS:
      Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies
      which examined serotonin sensitivity of receptor radioligands. PET-measured cross
      species differential effects of SSRI on cortical serotonin concentration may thus
      be related to SSRI dose. Future monkey studies using SSRI doses inducing
      clinically relevant SERT occupancy may further illuminate the delayed onset of
      SSRI therapeutic effects.

PMID- 25980486
TI  - Biological Function of G-Quadruplex Nucleic Acids and Potential Application in
      Medicinal Chemistry.

PMID- 25980485
TI  - Individual variation in the motivational properties of a nicotine cue: sign
      trackers vs. goal-trackers.
AB  - RATIONALE: Individuals vary in the extent to which they attribute incentive
      salience to reward cues. Discrete food and drug (cocaine and opioid) cues become
      more attractive, eliciting approach toward them, and more "wanted," in that they
      serve as more effective conditioned reinforcers, in some rats (sign-trackers,
      STs), than in others (goal-trackers, GTs). OBJECTIVES: We asked whether there is
      similar variation in the extent to which a cue associated with a drug from
      another class, nicotine, acquires incentive motivational properties. METHODS:
      First, a Pavlovian conditioned approach procedure was used to identify rats that
      attribute incentive salience to a food cue (i.e., STs and GTs). We then measured
      the extent to which a cue (a light) paired with intravenous nicotine injections
      acquired two properties of an incentive stimulus: (1) the ability to elicit
      approach toward it, and (2) the ability to act as a conditioned reinforcer.
      RESULTS: In contrast to previous findings with food, cocaine, and opioid cues, we
      found that the nicotine cue was equally attractive in STs and GTs, eliciting dose
      dependent approach behavior in both. However, the nicotine cue was a more
      effective conditioned reinforcer in STs than in GTs. CONCLUSIONS: We suggest the
      dissociation between these two measures of incentive salience attribution may be
      related to the fact that when present (as in the test of Pavlovian approach),
      nicotine can act as a potent "incentive amplifier," and by this action, nicotine
      may render cues especially salient for all animals.

PMID- 25980487
TI  - Different acute toxicity of fipronil baits on invasive Linepithema humile
      supercolonies and some non-target ground arthropods.
AB  - Fipronil is one of the most effective insecticides to control the invasive ant
      Linepithema humile, but its effectiveness has been assessed without considering
      the genetic differences among L. humile supercolonies. We hypothesized that the
      susceptibility of the ant to fipronil might differ among supercolonies. If so,
      dosage and concentration of fipronil may need to be adjusted for effective
      eradication of each supercolony. The relative sensitivities of four L. humile
      supercolonies established in Hyogo (Japan) to fipronil baits were examined based
      on their acute toxicity (48-h LC(50)). Toxicities of fipronil to seven ground
      arthropods, including four native ant species, one native isopoda, and two
      cockroaches were also determined and compared to that of L. humile supercolonies
      using species sensitivity distributions. Marked differences in susceptibility of
      fipronil were apparent among the supercolonies (P < 0.008), with the 'Japanese
      main supercolony' (271 MUg L(-1)) being five to ten times more sensitive to
      fipronil than other colonies (1183-2782 MUg L(-1)). Toxicities to non-target
      species (330-2327 MUg L(-1)) were in the same range as that of L. humile, and
      SSDs between the two species groups were not significantly different (t = -1.389,
      P = 0.180), suggesting that fipronil's insecticidal activity is practically the
      same for L. humile as for non-target arthropods. Therefore, if the invasive ant
      is to be controlled using fipronil, this would also affect the local arthropod
      biodiversity. Only the 'Japanese main supercolony' can be controlled with
      appropriate bait dosages of fipronil that would have little impact on the other
      species.

PMID- 25980488
TI  - Cloning and expression analysis of HSP70 gene from mangrove plant Kandelia
      obovata under cold stress.
AB  - Heat shock protein 70 (HSP70), the primary member of the HSPs that play various
      stress-protective roles in plants. In this study, a hsp70 gene of Kandelia
      obovata (KoHsp70) was cloned by rapid amplification of cDNA ends (RACE). The full
      length of KoHsp70 was 2255 bp, consisting of a 5'-terminal untranslated region
      (UTR) of 118 bp, a 3'-terminal UTR of 178 bp, and an open reading frame (ORF) of
      1959 bp. The ORF (KoHSP70) was predicted to encode a polypeptide of 652 amino
      acids with a theoretical molecular weight (MW) of 71.40 kDa and a pI of 5.16. The
      amino acid sequence analysis revealed that the KoHSP70 contained three conserved
      regions of HSP70 family, a bipartite nuclear localization signal sequences (NLS),
      an ATP/GTP-binding site motif and a cytoplasmic characteristic motif (EEVD).
      Homology analysis indicated that KoHSP70 shared 96.0 % identity with the known
      HSP70 (Gossypium hirsutum). Bioinformatics analysis indicated that the KoHSP70
      was hydrophilic and had no signal peptide or transmembrane region. The mRNA
      expression of KoHsp70 kept relatively stable at first and then increased
      significantly after 48 h cold stress, and reached the highest level at 168 h
      after cold treatment. The results indicated that the KoHsp70 was a stress
      inducible gene that might play a role in cold stress-protective response and in
      coping with environmental and biological stresses for K. obovata. This study
      provided a basis to further study the mechanism of anti-adverseness and
      expression characteristics under stress conditions of K. obovata.

PMID- 25980489
TI  - Identification of suitable reference genes in mangrove Aegiceras corniculatum
      under abiotic stresses.
AB  - Gene expression studies could provide insight into the physiological mechanisms
      and strategies used by plants under stress conditions. Selection of suitable
      internal control gene(s) is essential to accurately assess gene expression
      levels. For the mangrove plant, Aegiceras corniculatum, reliable reference genes
      to normalize real-time quantitative PCR data have not been previously
      investigated. In this study, the expression stabilities of five candidate
      reference genes [glyceraldehydes-3-phosphate dehydrogenase (GAPDH), 18SrRNA, beta
      Actin, 60S ribosomal protein L2, and elongation factor-1-A] were determined in
      leaves of A. corniculatum treated by cold, drought, salt, heavy metals, and
      pyrene and in different tissues of A. corniculatum under normal condition. Two
      software programs (geNorm and NormFinder) were employed to analyze and rank the
      tested genes. Results showed that GAPDH was the most suitable reference gene in
      A. corniculatum and the combination of two or three genes was recommended for
      greater accuracy. To assess the value of these tested genes as internal controls,
      the relative quantifications of CuZnSOD gene were also conducted. Results showed
      that the relative expression levels of CuZnSOD gene varied depending on the
      internal reference genes used, which highlights the importance of the choice of
      suitable internal controls in gene expression studies. Furthermore, the results
      also confirmed that GAPDH was a suitable reference gene for qPCR normalization in
      A. corniculatum under abiotic stresses. Identification of A. corniculatum
      reference gens in a wide range of experimental samples will provide a useful
      reference in future gene expression studies in this species, particularly
      involving similar stresses.

PMID- 25980490
TI  - The role of cyclooxygenase-2 and prostaglandin E2 in the pathogenesis of
      cutaneous lichen planus.
AB  - BACKGROUND: Lichen planus (LP) is an inflammatory disease of the skin and mucous
      membranes. Autoimmunity has been suggested as a possible cause of this disease.
      The cyclooxygenase enzymes (COX-1, COX-2) are the key enzymes in the conversion
      of arachidonic acid into prostaglandins. Prostaglandin E2 (PGE2), a key product
      of COX-2, has an immunomodulatory role. AIM: To map levels of COX-2 and PGE2 in
      cutaneous LP lesions and evaluate their role in the pathogenesis of the disease.
      METHODS: In total, 31 patients with classic cutaneous LP and 30 age- and sex
      matched healthy controls were enrolled. Skin biopsies were taken from the
      lesional and nonlesional skin of patients, and from the normal skin of controls.
      COX-2 mRNA expression was detected by real-time reverse transcription
      quantitative PCR, and PGE2 was detected by ELISA in skin biopsies from patients
      and controls. RESULTS: Our analysis revealed a significantly higher expression of
      COX-2 mRNA and PGE2 in the LP skin biopsies compared with the control biopsies (P
      < 0.001 and P < 0.001, respectively). Lesional biopsies showed significantly
      higher expression of COX-2 mRNA and PGE2 compared with nonlesional biopsies. The
      levels of COX-2 and PGE2 were not found to be correlated with age, sex or disease
      duration. CONCLUSIONS: COX-2 and its product PGE2 are strongly expressed in LP
      skin lesions, indicating that they have a role in the pathogenesis of LP through
      their immunomodulatory effects.

PMID- 25980491
TI  - Traumatic ossicular disruption with intact tympanic membrane: treatment
      modalities in 42 patients: Our experience.

PMID- 25980492
TI  - Deregulation of focal adhesion pathway mediated by miR-659-3p is implicated in
      bone marrow infiltration of stage M neuroblastoma patients.
AB  - To get insights on the metastatic process of human neuroblastoma (NB), the miRNA
      expression profile of bone marrow (BM)-infiltrating cells has been determined and
      compared to that of primary tumors.Twenty-two BM-infiltrating cells, 22 primary
      tumors, and 4 paired samples from patients with metastatic NB aged > 12 months
      were analyzed for the expression of 670 miRNAs by stem-loop RT-qPCR. The miRNAs
      whose expression was significantly different were subjected to selection
      criteria, and 20 selected miRNAs were tested in 10 additional BM-infiltrating
      cells and primary tumors. Among the miRNAs confirmed to be differentially
      expressed, miR-659-3p was further analyzed. Transfection of miR-659-3p mimic and
      inhibitor demonstrated the specific suppression and over-expression,
      respectively, of the miR-659-3p target gene CNOT1, a regulator of transcription
      of genes containing AU-rich element (ARE) sequence. Among the ARE-containing
      genes, miR-659-3p mimic and inhibitor specifically modified the expression of
      AKT3, BCL2, CYR61 and THSB2, belonging to the focal adhesion pathway. Most
      importantly, in BM-infiltrating cells CNOT1 expression was significantly higher,
      and that of AKT3, BCL2, THSB2 and CYR61 was significantly lower than in primary
      tumors. Thus, our study suggests a role of the focal adhesion pathway, regulated
      by miR-659-3p through CNOT1, in the human NB metastatic process. 

PMID- 25980493
TI  - Nuclear EGFR impairs ASPP2-p53 complex-induced apoptosis by inducing SOS1
      expression in hepatocellular carcinoma.
AB  - ASPP2 can bind to p53 and enhance the apoptotic capabilities of p53 by guiding it
      to the promoters of pro-apoptotic genes. Here, ASPP2 overexpression for 24 hours
      transiently induced apoptosis in hepatoma cells by enhancing the transactivation
      of p53 on pro-apoptotic gene promoters. However, long-term ASPP2 overexpression
      (more than 48 hours) failed to induce apoptosis because p53 was released from the
      pro-apoptotic gene promoters. In non-apoptotic cells, nuclear EGFR induced SOS1
      expression by directly binding to the SOS1 promoter. SOS1 activated the
      HRAS/PI3K/AKT pathway and resulted in nuclear translocation of p-AKT and Bcl-2.
      The interaction between p-AKT and ASPP2 facilitates Bcl-2 binding to p53, which
      releases p53 from the pro-apoptotic gene promoters. The in vivo assay
      demonstrated that EGFR/SOS1-promoted growth of nuclear p-AKT+, Bcl-2+ cells
      results in the resistance of hepatoma cells to ASPP2-p53 complex-induced
      apoptosis and that blocking nuclear translocation of EGFR dramatically improves
      and enhances the pro-apoptotic function of ASPP2. Finally, the activation of the
      HRAS/PI3K/AKT pathway by EGFR-induced SOS1 also inhibits cisplatin-induced
      apoptosis, suggesting a common apoptosis-evasion mechanism in hepatoma cells.
      Because evasion of apoptosis contributes to treatment resistance in hepatoma, our
      results also support further investigation of combined therapeutic blockade of
      EGFR and SOS1.

PMID- 25980494
TI  - Cyr61 as mediator of Src signaling in triple negative breast cancer cells.
AB  - SFKs are involved in tumorigenesis and metastasis. Here we analyzed c-Src
      contribution to initial steps of metastasis by tetracycline-dependent expression
      of a specific shRNA-c-Src, which suppressed c-Src mRNA and protein levels in
      metastatic MDA-MB-231 cells. c-Src suppression did not alter cell proliferation
      or survival, but it significantly reduced anchorage-independent growth.
      Concomitantly with diminished tyrosine-phosphorylation/activation of Fak,
      caveolin-1, paxillin and p130CAS, c-Src depletion also inhibited cellular
      migration, invasion and transendothelial migration. Quantitative proteomic
      analyses of the secretome showed that Cyr61 levels, which were detected in the
      exosomal fraction, were diminished upon shRNA-c-Src expression. In contrast,
      Cyr61 expression was unaltered inside cells. Cyr61 partially colocalized with cis
      Golgi gp74 marker and with exosomal marker CD63, but c-Src depletion did not
      alter their cellular distribution. In SUM159PT cells, transient c-Src suppression
      also reduced secreted exosomal Cyr61 levels. Furthermore, conditional expression
      of a c-Src dominant negative mutant (SrcDN, c-Src-K295M/Y527F) in MDA-MB-231 and
      in SUM159PT diminished secreted Cyr61 as well. Cyr61 transient suppression in MDA
      MB-231 inhibited invasion and transendothelial migration. Finally, in both MDA-MB
      231 and SUM159PT, a neutralizing Cyr61 antibody restrained migration.
      Collectively, these results suggest that c-Src regulates secreted proteins,
      including the exosomal Cyr61, which are involved in modulating the metastatic
      potential of triple negative breast cancer cells. 

PMID- 25980495
TI  - Inhibition of colorectal cancer stem cell survival and invasive potential by hsa
      miR-140-5p mediated suppression of Smad2 and autophagy.
AB  - Colorectal cancer (CRC) is the third highest mortality cancer in the United
      States and frequently metastasizes to liver and lung. Smad2 is a key element
      downstream of the TGF-beta signaling pathway to regulate cancer metastasis by
      promoting epithelial to mesenchymal transition and maintaining the cancer stem
      cell (CSC) phenotype. In this study, we show that hsa-miR-140-5p directly targets
      Smad2 and overexpression of hsa-miR-140-5p in CRC cell lines decreases Smad2
      expression levels, leading decreased cell invasion and proliferation, and
      increasing cell cycle arrest. Ectopic expression of hsa-miR-140-5p in colorectal
      CSCs inhibited CSC growth and sphere formation in vitro by disrupting autophagy.
      We have systematically identified targets of hsa-miR-140-5p involved in
      autophagy. Furthermore, overexpression of hsa-miR-140-5p in CSCs abolished tumor
      formation and metastasis in vivo. In addition, there is a progressive loss of hsa
      miR-140-5p expression from normal colorectal mucosa to primary tumor tissues,
      with further reduction in liver metastatic tissues. Higher hsa-miR-140 expression
      is significantly correlated with better survival in stage III and IV colorectal
      cancer patients.The functional and clinical significance of hsa-miR-140-5p
      suggests that it is a key regulator in CRC progression and metastasis, and may
      have potential as a novel therapeutic molecule to treat CRC. 

PMID- 25980497
TI  - TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer
      cells.
AB  - The cold and menthol receptor TRPM8 is highly expressed in prostate and prostate
      cancer (PC). Recently, we identified that TRPM8 is as an ionotropic testosterone
      receptor. The TRPM8 mRNA is expressed in early prostate tumors with high androgen
      levels, while anti-androgen therapy greatly reduces its expression. Here, from
      the chromatin-immunoprecipitation (ChIP) analysis, we found that an androgen
      response element (ARE) mediates androgen regulation of trpm8. Furthermore, using
      immunofluorescence, calcium-imaging and planar lipid bilayers, we identified that
      TRPM8 channel is functionally regulated by androgens in the prostate. Although
      TRPM8 mRNA is expressed at high levels, we found that the TRPM8 protein undergoes
      ubiquitination and degradation in PC cells. The mass-spectrometry analysis of
      TRPM8, immunoprecipitated from LNCaP cells identified ubiquitin-like modifier
      activating enzyme 1 (UBA1). PYR-41, a potent inhibitor of initial enzyme in the
      ubiquitination cascade, UBA1, increased TRPM8 activity on the plasma membrane
      (PM) of LNCaP cells. Furthermore, PYR-41-mediated PMTRPM8 activity was
      accompanied by enhanced activation of p53 and Caspase-9. Interestingly, we found
      that the trpm8 promoter possesses putative binding sites for p53 and that the
      overexpression of p53 increased the TRPM8 mRNA levels. In addition to the genomic
      regulation of TRPM8 by AR and p53, our findings indicate that the testosterone
      induced PMTRPM8 activity elicits Ca2+ uptake, subsequently causing apoptotic cell
      death. These findings support the strategy of rescuing PMTRPM8 expression as a
      new therapeutic application through the regulation of PC cell growth and
      proliferation. 

PMID- 25980496
TI  - miR-514a regulates the tumour suppressor NF1 and modulates BRAFi sensitivity in
      melanoma.
AB  - To identify 'melanoma-specific' microRNAs (miRNAs) we used an unbiased microRNA
      profiling approach to comprehensively study cutaneous melanoma in relation to
      other solid malignancies, which revealed 233 differentially expressed (>= 2 fold,
      p < 0.05) miRNAs. Among the top 20 most significantly different miRNAs was hsa
      miR-514a-3p. miR-514a is a member of a cluster of miRNAs (miR-506-514) involved
      in initiating melanocyte transformation and promotion of melanoma growth. We
      found miR-514a was expressed in 38/55 (69%) melanoma cell lines but in only 1/34
      (3%) other solid cancers. To identify miR-514a regulated targets we conducted a
      miR-514a-mRNA 'pull-down' experiment, which revealed hundreds of genes,
      including: CTNNB1, CDK2, MC1R, and NF1, previously associated with melanoma. NF1
      was selected for functional validation because of its recent implication
      inacquired resistance to BRAFV600E-targeted therapy. Luciferase-reporter assays
      confirmed NF1 as a direct target of miR-514a and over-expression of miR-514a in
      melanoma cell lines inhibited NF1 expression, which correlated with increased
      survival of BRAFV600E cells treated with PLX4032. These data provide another
      mechanism for the dysregulation of the MAPK pathway which may contribute to the
      profound resistance associated with current RAF-targeted therapies. 

PMID- 25980498
TI  - Pharmacogenomic analysis indicates potential of 1,5-isoquinolinediol as a
      universal anti-aging agent for different tissues.
AB  - The natural aging of multicellular organisms is marked by a progressive decline
      in the function of cells and tissues. The accumulation of senescent cells in
      tissues seems to eventually cause aging of the host. Nevertheless, gene
      expression that influences aging is unlikely to be conserved between tissues, and
      age-related loss of function seems to depend on a variety of mechanisms. This is
      a concern when developing anti-aging drugs in geriatric clinical pharmacology. We
      have sought a universal agent to redundantly cover gene expression despite the
      variation in differentially expressed genes between tissues. Using a minimally
      modified connectivity map, the poly (ADP-ribose) polymerase (PARP) inhibitor 1,5
      isoquinolinediol was selected as a potent candidate, simultaneously applicable to
      various tissues. This choice was validated in vitro. Treatment of murine
      embryonic fibroblasts with 1,5-isoquinolinediol appeared to efficiently suppress
      the rate of replicative senescence at a concentration of 0.1 uM without resulting
      in cell death. The appearance of abnormal nuclei and accumulation of beta
      galactosidase in the cytoplasm were inhibited by daily treatment with the agent.
      When the aging process was accelerated by hydroxyurea-induced oxidative stress,
      the effect was even more noticeable. Thus, 1,5-isoquinolinediol may potentially
      be developed as an agent to prolong life. 

PMID- 25980499
TI  - Small molecule inhibition of Axl receptor tyrosine kinase potently suppresses
      multiple malignant properties of glioma cells.
AB  - Glioblastoma multiforme (GBM) often features a combination of tumour suppressor
      gene inactivation and multiple oncogene overactivation. The Axl receptor tyrosine
      kinase is found overexpressed in GBM and thought to contribute to invasiveness,
      chemoresistance and poor survival. Here, we have evaluated the effect of BGB324,
      a clinical candidate Axl-specific small molecule inhibitor, on the invasive
      behaviour of human GBM cells in vitro, as an indicator of its potential in GBM
      therapy and also to elucidate the role of Axl in GBM pathogenesis.Two cultured
      adult GBM cell lines, SNB-19 and UP007, were treated with Gas6 and/or BGB324, and
      analysed in assays for survival, 3D colony growth, motility, migration and
      invasion. Western blot was used to detect protein expression and signal protein
      phosphorylation. In both cell lines, BGB324 inhibited specifically
      phosphorylation of Axl as well as Akt kinase further downstream. BGB324 also
      inhibited survival and proliferation of both cell lines in a concentration
      dependent manner, as well as completely suppressing migration and invasion.
      Furthermore, our results indicate co-operative activation between the Axl and
      Tyro3 receptors, as well as ligand-independent Axl signalling, to take place in
      GBM cells. In conclusion, small molecule inhibitor-led targeting of Axl may be a
      promising therapy for GBM progression.

PMID- 25980500
TI  - The IgH 3' regulatory region influences lymphomagenesis in Iglambda-Myc mice.
AB  - The IgH 3'regulatory region (3'RR), encompassing the four transcriptional
      enhancers hs3a-hs1,2-hs3b-hs4, has a key role on class switch recombination,
      somatic hypermutation, IgH transcription and B-cell fate. In plasma cells,
      transcribed IgH and IgL loci often colocalized in transcription factories and an
      IgL transcription defect might translate into lowered IgH transcription. We
      explored whether the 3'RR would affect lymphomagenesis in Iglambda-Myc transgenic
      mice prone to lymphoproliferations. Breeding Iglambda-Myc transgenics in a
      background deficient for the 3'RR influences lymphomagenesis toward less mature
      lymphomas (16% vs 54%, p = 0.01, Z test for two population proportions). In a
      3'RR-deficient background mature tumors less often expressed the CD43 antigen
      (54% vs 0%, p = 0.02), a membrane glycoprotein expressed on activated mature B
      cells. In contrast, in a 3'RR-deficient background tumors more often expressed
      the CD5 antigen (32% vs 12%, p = 0.05) that may serve to control autoimmunity and
      that is suspected to play a role in leukemic transformation. Lymphoma myc
      transcript levels, the Ki67 index of proliferation, the clonality, the usage of
      V(D)J segments, and their somatic hypermutation status were not affected in the
      3'RR-deficient background. In conclusion, most probably through its action during
      the maturation process, the 3'RR can influence lymphomagenesis even when not
      linked with an oncogene.

PMID- 25980501
TI  - Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in
      mice by inhibiting the Wnt pathway in the tumor microenvironment.
AB  - Wnt/beta-catenin signaling is responsible for the generation of cancer stem cells
      (CSCs) in many human tumors, including nasopharyngeal carcinoma (NPC). Recent
      studies demonstrate that Wnt or PORCN inhibitor, Wnt-C59, inhibits tumor growth
      in MMTV-WNT1 transgenic mice. The effect of Wnt-C59 in human tumors is not clear.
      In this study, the NPC cell lines investigated manifest heterogeneous responses
      to Wnt-C59 treatment. Wnt-C59 decreased tumor growth of SUNE1 cells in mice
      immediately following the administration of Wnt-C59. Mice injected with HNE1
      cells did not develop visible tumors after the treatment of Wnt-C59, while
      control mice developed 100% tumors. Wnt-C59 inhibited stemness properties of NPC
      cells in a dosage-dependent manner by arresting sphere formation in both HNE1 and
      SUNE1 cells. Thus, Wnt-C59 has the potential to eradicate CSCs in human tumors.
      Active beta-catenin and Axin2 proteins were strongly expressed in stromal cells
      surrounding growing tumors, confirming the importance of Wnt signaling activities
      in the microenvironment being driving forces for cell growth. These novel
      findings confirm the ability of Wnt-C59 to suppress Wnt-driven undifferentiated
      cell growth in NPC. Both anti-Wnt signaling and anti-CSC approaches are feasible
      strategies in cancer therapy. 

PMID- 25980502
TI  - Effect of Severe Maternal Iron Deficiency Anemia on Neonatal Platelet Indices.
AB  - OBJECTIVE: To evaluate the effect of maternal iron deficiency anemia (IDA) on
      fetal thrombopoiesis. METHODS: In this prospective observational study, maternal
      and cord blood iron status parameters (serum iron, serum ferritin, total iron
      binding capacity, and transferrin saturation), and platelet indices, such as,
      absolute platelet count (APC), mean platelet volume (MPV), platelet distribution
      width (PDW) and plateletcrit, were estimated in a convenient sample of 142
      mothers with IDA (hemoglobin <11 g/dl and serum ferritin <12 ng/ml) and an equal
      number of healthy non-anemic (hemoglobin >=11 g/dl) mothers, who delivered
      singleton live neonates at term gestation. Mothers with antenatal
      thrombocytopenia, infections, inflammatory conditions, pregnancy-induced
      hypertension and neonates with perinatal asphyxia, sepsis and congenital
      malformations were excluded. RESULTS: For statistical analysis, the IDA group was
      further subdivided into mild-to-moderate (hemoglobin 7-10.9 g/dl) and severe
      (hemoglobin <7 g/dl) anemia. Cord blood APC and PDW were comparable between non
      anemic and mild-to-moderate anemic mothers (242,550 +/- 54,320/MUL vs. 235,260 +/
      34,620/MUL for APC and 16.2 +/- 1.4 vs. 16.4 +/- 1.8 fl for PDW, respectively),
      but in severe IDA group, cord blood APC and PDW were significantly lower (74,520
      +/- 12,380/MUL and 17.8 +/- 2.1 fl, respectively, p < 0.001). MPV and
      plateletcrit were comparable. None of the study neonates had a platelet count
      <30,000/MUL or showed any evidence of clinical bleeding. CONCLUSIONS: Neonates
      born to mothers with severe IDA had moderate thrombocytopenia with increased PDW,
      though no change was observed in MPV and plateletcrit. Further studies should be
      carried out to identify the cause and consequences of this observation.

PMID- 25980503
TI  - The impact of signal normalization on seizure detection using line length
      features.
AB  - Accurate automated seizure detection remains a desirable but elusive target for
      many neural monitoring systems. While much attention has been given to the
      different feature extractions that can be used to highlight seizure activity in
      the EEG, very little formal attention has been given to the normalization that
      these features are routinely paired with. This normalization is essential in
      patient-independent algorithms to correct for broad-level differences in the EEG
      amplitude between people, and in patient-dependent algorithms to correct for
      amplitude variations over time. It is crucial, however, that the normalization
      used does not have a detrimental effect on the seizure detection process. This
      paper presents the first formal investigation into the impact of signal
      normalization techniques on seizure discrimination performance when using the
      line length feature to emphasize seizure activity. Comparing five normalization
      methods, based upon the mean, median, standard deviation, signal peak and signal
      range, we demonstrate differences in seizure detection accuracy (assessed as the
      area under a sensitivity-specificity ROC curve) of up to 52 %. This is despite
      the same analysis feature being used in all cases. Further, changes in
      performance of up to 22 % are present depending on whether the normalization is
      applied to the raw EEG itself or directly to the line length feature. Our results
      highlight the median decaying memory as the best current approach for providing
      normalization when using line length features, and they quantify the under
      appreciated challenge of providing signal normalization that does not impair
      seizure detection algorithm performance. 

PMID- 25980504
TI  - Biomechanical behavior of human crural fascia in anterior and posterior regions
      of the lower limb.
AB  - The present work focuses on the numerical modeling of the mechanical behavior of
      the crural fascia, the deep fascia enwrapping the lower limb muscles. This fascia
      has an important biomechanical role, due to its interaction with muscles during
      contraction and its association with pathological events, such as compartment
      syndrome. The mechanical response of the crural fascia is described by assuming a
      hyperelastic fiber-reinforced constitutive model, with families of fibers
      disposed according to the spatial disposition of the collagen network, as shown
      in histological analyses. A two-dimensional finite element model of a lower limb
      transversal section has been developed to analyze deformational behavior, with
      particular attention on interaction phenomena between crural fascia and enwrapped
      muscles. The constitutive model adopted for the crural fascia well fits
      experimental data taken along the proximal-distal and medial-lateral directions.
      The finite element analysis allows for interpreting the relation between change
      in volume and pressure of muscle compartments and the crural fascia deformation. 

PMID- 25980505
TI  - Predictive classification of self-paced upper-limb analytical movements with EEG.
AB  - The extent to which the electroencephalographic activity allows the
      characterization of movements with the upper limb is an open question. This paper
      describes the design and validation of a classifier of upper-limb analytical
      movements based on electroencephalographic activity extracted from intervals
      preceding self-initiated movement tasks. Features selected for the classification
      are subject specific and associated with the movement tasks. Further tests are
      performed to reject the hypothesis that other information different from the task
      related cortical activity is being used by the classifiers. Six healthy subjects
      were measured performing self-initiated upper-limb analytical movements. A
      Bayesian classifier was used to classify among seven different kinds of
      movements. Features considered covered the alpha and beta bands. A genetic
      algorithm was used to optimally select a subset of features for the
      classification. An average accuracy of 62.9 +/- 7.5% was reached, which was above
      the baseline level observed with the proposed methodology (30.2 +/- 4.3%). The
      study shows how the electroencephalography carries information about the type of
      analytical movement performed with the upper limb and how it can be decoded
      before the movement begins. In neurorehabilitation environments, this information
      could be used for monitoring and assisting purposes.

PMID- 25980506
TI  - Biological correlates of child and adolescent responses to disaster exposure: a
      bio-ecological model.
AB  - Exposure to both human-caused and natural disasters is associated with a number
      of postevent reactions in youth including the experience of symptoms of several
      mental disorders. There is wide variability in these responses, with some youth
      having very intense exposure to the disaster and yet showing resilience or even
      personal growth, while others with low exposure sometimes show intensely negative
      reactions. Research findings are reviewed in this article to identify biological
      correlates of risk and resilience focusing on potential genetic, neurobiological,
      and physiological factors linked to the reactions of children exposed to
      disasters. A bio-ecological model is presented to couch this review of biological
      correlates of disaster exposure. The model predicts susceptibility to negative
      reactions after disaster exposure, and the biological correlates of disaster
      reactions can be understood in terms of this susceptibility as it relates to
      biological markers of the fear system. 

PMID- 25980507
TI  - Assessment and treatment of anxiety disorders in children and adolescents.
AB  - Recent advances in the developmental epidemiology, neurobiology, and treatment of
      pediatric anxiety disorders have increased our understanding of these conditions
      and herald improved outcomes for affected children and adolescents. This article
      reviews the current epidemiology, longitudinal trajectory, and neurobiology of
      anxiety disorders in youth. Additionally, we summarize the current evidence for
      both psychotherapeutic and psychopharmacologic treatments of fear-based anxiety
      disorders (e.g., generalized, social, and separation anxiety disorders) in
      children and adolescents. Current data suggest that these disorders begin in
      childhood and adolescence, exhibit homotypic continuity, and increase the risk of
      secondary anxiety and mood disorders. Psychopharmacologic trials involving
      selective serotonin reuptake inhibitors (SSRIs) and selective serotonin
      norepinephrine reuptake inhibitors (SSNRIs) are effective in pediatric patients
      with anxiety disorders and have generally demonstrated moderate effect sizes.
      Additionally, current data support cognitive behavioral therapy (CBT) for the
      treatment of these conditions in youth and suggest that the combination of
      psychotherapy + an SSRI may be associated with greater improvement than would be
      expected with either treatment as monotherapy.

PMID- 25980508
TI  - Neuroimaging and sexual behavior: identification of regional and functional
      differences.
AB  - The neuroanatomical correlates of human sexual desire, arousal, and behavior have
      been characterized in recent years with functional brain imaging techniques such
      as magnetic resonance imaging (MRI) and positron emission tomography (PET). Here,
      we briefly review the results of functional neuroimaging studies in humans,
      whether healthy or suffering from sexual disorders, and the current models of
      regional and network activation in sexual arousal. Attention is paid, in
      particular, to findings from both regional and network studies in the past 3
      years. We also identify yet unanswered and pressing questions of interest to
      areas of ongoing investigations for psychiatric, scientific, and forensic
      disciplines.

PMID- 25980511
TI  - Sexual assault in the military.
AB  - Military sexual assault is a pervasive problem throughout the military services,
      despite numerous initiatives to end it. No doubt the military's lack of progress
      stems from the complexity of sexual assaults, yet in order to develop effective
      strategies and programs to end sexual assault, deep understanding and
      appreciation of these complexities are needed. In this paper, we describe the
      root causes and numerous myths surrounding sexual assault, the military cultural
      factors that may unintentionally contribute to sexual assault, and the
      uncomfortable issues surrounding sexual assault that are often ignored (such as
      the prevalence of male sexual assault within the military). We conclude by
      offering a broad, yet comprehensive set of recommendations that considers all of
      these factors for developing effective strategies and programs for ending sexual
      assault within in the military.

PMID- 25980510
TI  - New research on anxiety disorders in the elderly and an update on evidence-based
      treatments.
AB  - Anxiety disorders are frequently encountered in the elderly, but they are largely
      undetected and untreated. Epidemiological studies indicate a prevalence ranging
      from 1.2 to 15 %. With the exception of generalized anxiety disorder and
      agoraphobia, which can often start in late life, most anxiety disorders in older
      patients are chronic and have their onset earlier in life. Anxiety disorders are
      an often unrecognized cause of distress, disability, and mortality risk in older
      adults, and they have been associated with cardiovascular disease, stroke, and
      cognitive decline. The mechanisms of anxiety in older adults differ from that in
      younger adults due to age-related neuropathology, as well as the loss and
      isolation so prominent in late life. Our review intends to provide a
      comprehensive summary of the most recent research done in the field of anxiety
      disorders in the elderly. Recent findings in clinical research, neuroimaging,
      neuroendocrinology, and neuropsychology are covered. An update on treatment
      options is discussed, including pharmacological and non-pharmacological
      alternatives.

PMID- 25980509
TI  - Pharmacogenetics of major depressive disorder: top genes and pathways toward
      clinical applications.
AB  - The pharmacogenetics of antidepressants has been not only a challenging but also
      frustrating research field since its birth in the 1990s. Indeed, great
      expectations followed the first evidence of familiar aggregation of
      antidepressant response. Despite the progress from candidate gene studies to
      genome-wide association studies (GWAS), results fell out the expectations and
      they were often inconsistent. Anyway, the cumulative evidence supports the
      involvement of some genes and molecular pathways in antidepressant efficacy. The
      best single genes are SLC6A4, HTR2A, BDNF, GNB3, FKBP5, ABCB1, and cytochrome
      P450 genes (CYP2D6 and CYP2C19). Molecular pathways involved in inflammation and
      neuroplasticity show the greatest support. The first studies evaluating benefits
      of genotype-guided antidepressant treatments provided encouraging results and
      confirmed the relevance of SLC6A4, HTR2A, ABCB1, and cytochrome P450 genes.
      Further progress in genotyping and data analysis would allow to move forward and
      complete the understanding of antidepressant pharmacogenetics and its translation
      into clinical applications.

PMID- 25980513
TI  - Children's disaster reactions: the influence of exposure and personal
      characteristics.
AB  - This paper reviews children's reactions to disasters and the personal and
      situational factors that influence their reactions. Posttraumatic stress disorder
      (PTSD) and posttraumatic stress reactions are the most commonly studied outcomes,
      though other conditions also occur including anxiety, depression, behavior
      problems, and substance use. More recently, traumatic grief and posttraumatic
      growth have been explored. New research has delineated trajectories of children's
      posttraumatic stress reactions and offered insight into the long-term
      consequences of their disaster experiences. Risk factors for adverse outcomes
      include pre-disaster vulnerabilities, perception of threat, and loss and life
      disruptions post-disaster. Areas in need of additional research include studies
      on the timing and course of depression and anxiety post-event and their
      interactions with other disorders, disaster-related functional and cognitive
      impairment, positive outcomes, and coping.

PMID- 25980512
TI  - Children's disaster reactions: the influence of family and social factors.
AB  - This review examines family (demographics, parent reactions and interactions, and
      parenting style) and social (remote effects, disaster media coverage, exposure to
      secondary adversities, and social support) factors that influence children's
      disaster reactions. Lower family socioeconomic status, high parental stress, poor
      parental coping, contact with media coverage, and exposure to secondary
      adversities have been associated with adverse outcomes. Social support may
      provide protection to children in the post-disaster environment though more
      research is needed to clarify the effects of certain forms of social support. The
      interaction of the factors described in this review with culture needs further
      exploration.

PMID- 25980514
TI  - Frail elder caries.

PMID- 25980518
TI  - Shell-engineering of hollow g-C3N4 nanospheres via copolymerization for
      photocatalytic hydrogen evolution.
AB  - Incorporation of aromatic motifs into the nanosized shells of hollow carbon
      nitride nanospheres has been reported to develop functional photosynthetic
      structures for solar energy application. This modification results in an extended
      pi-conjugation system, red-shift of the optical absorption, and an improved
      charge separation in the shell, while still retaining the unique hollow polymeric
      nanoarchitectures. This strategy enables the tuning of the semiconductor
      properties of the shell substance in the hollow carbon nitride nanostructures to
      generate the redox species to enhance photocatalytic activity for hydrogen
      evolution using visible light. 

PMID- 25980517
TI  - PDGFRalpha demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in
      adult murine myocardium.
AB  - Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic
      target for heart regeneration, though (inter)-relationships among reported cells
      remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define
      four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium
      all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype,
      PECAM-1 (CD31) and platelet-derived growth factor receptor-alpha (PDGFRalpha)
      expression. SP status predicts clonogenicity and cardiogenic gene expression
      (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to
      PDGFRalpha(+) cells. Clonal progeny of single Sca1(+) SP cells show
      cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac
      grafting, augmenting cardiac function although durable engraftment is rare.
      PDGFRalpha(-) cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of
      clonogenicity. PDGFRalpha(+)/CD31(-) cells derive from cells formerly expressing
      Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRalpha(-)/CD31(+) cells
      (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRalpha demarcates the clonogenic
      cardiogenic Sca1(+) stem/progenitor cell. 

PMID- 25980519
TI  - Kinetic index combining native and postcontrast myocardial T1 in hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: To evaluate ability of pre- and postcontrast apparent T1* indices, as
      well as their combination to characterize myocardial structural changes in
      hypertrophic cardiomyopathy (HCM). METHODS: Study protocol was approved by
      institutional review board and informed consent was obtained. T1 mapping was
      performed using MOLLI sequence (1.5T magnet) on: (i) tubes with known T1 and
      varied heart-rates (HR), (ii) 17 HCM (55 +/- 15 years) and 18 controls (49 +/- 16
      years), before contrast and every 5 min over 20 min postcontrast. Global and
      segmental native T1 (T1*Native ), extracellular volume (ECV) and percentage of
      decrease in myocardial T1* (T1*decay = 100.[1-T1*Post-contrast /T1*Native ]) were
      estimated. Correlation coefficients of associations between T1 and LV indices,
      such as left ventricular wall thickness (WT) and mass index (LVMi) were provided.
      Receiver operator curve analysis was performed on per-patient basis to assess
      ability of T1* indices to identify HCM. RESULTS: While up to a T1* of 1000 ms the
      effect of HR was minor, it was more pronounced above 1000 ms. T1*Native (754 +/-
      76 ms versus 1014 +/- 130 ms, P < 0.001), ECV20min (23 +/- 5% versus 27 +/- 4%, P
      = 0.005), and T1*decay5, 10, 15 or 20min (38 +/- 8% versus 54 +/- 6%, P < 0.001)
      showed significant differences between controls and HCM. Correlation coefficients
      for associations with WT and LVMi were higher for T1*Native and T1decay,
      independent of acquisition time (with WT/LVMi: r = 0.58/0.44 (P < 0.05) for
      T1*Native ; r = 0.23 (P < 0.05)/0.23 for ECV20min ; r > 0.51/ > 0.45(P < 0.05)
      for T1*decay5, 20min ). T1*Native (97.1%) and T1*decay (91.2%) characterized HCM
      with higher accuracy (P < 0.02) than ECV (69%). CONCLUSION: T1*Native and
      T1*decay were able to characterize HCM more accurately than ECV, even in the
      absence of myocardial hypertrophy and late-gadolinium enhancement.

PMID- 25980521
TI  - Impact of multiple transarterial chemoembolization treatments on hepatocellular
      carcinoma patients awaiting liver transplantation.

PMID- 25980520
TI  - A Naive Bayes machine learning approach to risk prediction using censored, time
      to-event data.
AB  - Predicting an individual's risk of experiencing a future clinical outcome is a
      statistical task with important consequences for both practicing clinicians and
      public health experts. Modern observational databases such as electronic health
      records provide an alternative to the longitudinal cohort studies traditionally
      used to construct risk models, bringing with them both opportunities and
      challenges. Large sample sizes and detailed covariate histories enable the use of
      sophisticated machine learning techniques to uncover complex associations and
      interactions, but observational databases are often 'messy', with high levels of
      missing data and incomplete patient follow-up. In this paper, we propose an
      adaptation of the well-known Naive Bayes machine learning approach to time-to
      event outcomes subject to censoring. We compare the predictive performance of our
      method with the Cox proportional hazards model which is commonly used for risk
      prediction in healthcare populations, and illustrate its application to
      prediction of cardiovascular risk using an electronic health record dataset from
      a large Midwest integrated healthcare system.

PMID- 25980522
TI  - Free Fecal Immunochemical Test Disbursement in Eight Family Physician Offices.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer death. CRC
      screening with a fecal immunochemical test (FIT) is important as occult blood may
      be detected. To offer Iowa Research Network members in family physician offices
      the opportunity to provide FITs at no charge to patients in need and determine
      how many of the tests would be handed out to patients and how many would be
      returned to the office. Eight family physician offices agreed to participate and
      50 two-day FITs were provided, potentially providing 400 patients a CRC screening
      test. One hundred and eighty (45%) of the 400 FITs were handed out to patients.
      Of the 92 (51%) patients who returned at least one card, 77 (84%) had negative
      results, 13 (14%) were positive, and 2 (2 %) were indeterminate. Of 13 patients
      with a positive result, 11 (85%) had a follow-up colonoscopy. Providing 400 FITs
      at no charge to the offices was an expensive endeavor. Implementing this forced a
      change in office routine and the type of fecal occult blood test used. Less than
      half of the FITs were given out to patients and of those given out, about half of
      the patients returned a FIT. For those who returned FITs and had positive
      findings, 85% followed-up with a colonoscopy. Office nurses implementing the CRC
      screening need to be included in the planning of the type of fecal occult blood
      test used and receptive to the project.

PMID- 25980523
TI  - Attitudes Toward Smoking Cessation Among Sheltered Homeless Parents.
AB  - The prevalence of smoking among homeless adults is approximately 70 %. Cessation
      programs designed for family shelters should be a high priority given the dangers
      cigarette smoke poses to children. However, the unique nature of smoking in the
      family shelter setting remains unstudied. We aimed to assess attitudes toward
      smoking cessation, and unique barriers and motivators among homeless parents
      living in family shelters in Northern California. Six focus groups and one
      interview were conducted (N = 33, ages 23-54). The focus groups and interviews
      were audiorecorded, transcribed verbatim, and a representative team performed
      qualitative theme analysis. Eight males and 25 females participated. The
      following major themes emerged: (1) Most participants intended to quit
      eventually, citing concern for their children as their primary motivation. (2)
      Significant barriers to quitting included the ubiquity of cigarette smoking, its
      central role in social interactions in the family shelter setting, and its
      importance as a coping mechanism. (3) Participants expressed interest in quitting
      "cold turkey" and in e-cigarettes, but were skeptical of the patch and
      pharmacotherapy. (4) Feelings were mixed regarding whether individual, group or
      family counseling would be most effective. Homeless parents may be uniquely
      motivated to quit because of their children, but still face significant shelter
      based social and environmental barriers to quitting. Successful cessation
      programs in family shelters must be designed with the unique motivations and
      barriers of this population in mind. 

PMID- 25980525
TI  - Variable flip angle T1 mapping in the human brain with reduced T2 sensitivity
      using fast radiofrequency-spoiled gradient echo imaging.
AB  - PURPOSE: Variable flip angle (VFA) T1 quantification using three-dimensional (3D)
      radiofrequency (RF) spoiled gradient echo imaging offers the acquisition of whole
      brain T1 maps in clinically acceptable times. However, conventional VFA T1
      relaxometry is biased by incomplete spoiling (i.e., residual T2 dependency). A
      new postprocessing approach is proposed to overcome this T2-related bias.
      METHODS: T1 is quantified from the signal ratio of two spoiled gradient echo
      (SPGR) images acquired at different flip angles using an analytical solution for
      the RF-spoiled steady-state signal in combination with a global T2 guess. T1
      accuracy is evaluated from simulations and in vivo 3D SPGR imaging of the human
      brain at 3 Tesla. RESULTS: The simulations demonstrated that the sensitivity of
      VFA T1 mapping to T2 can considerably be reduced using a global T2 guess. The
      method proved to deliver reliable and accurate T1 values in vivo for white and
      gray matter in good agreement with inversion recovery reference measurements.
      CONCLUSION: Based on a global T2 estimate, the accuracy of VFA T1 relaxometry in
      the human brain can substantially be improved compared with conventional
      approaches which rely on the generally wrong assumption of ideal spoiling.

PMID- 25980526
TI  - Factors associated with fetal losses in ewe lambs on a New Zealand sheep farm.
AB  - CASE HISTORY: As part of a production study of ewe lambs on a large farm in the
      Waikato region of New Zealand in 2011, pregnancy diagnosis was undertaken twice
      by trans-abdominal ultrasonography at 68-103 and 97-132 days of gestation. At the
      second pregnancy diagnosis 257/3,790 (6.8%) ewe lambs had evidence of non-viable
      fetuses or absence of a pregnancy that was present at the previous pregnancy
      diagnosis (fetal loss). LABORATORY FINDINGS: Serum antibody titres for Leptospira
      interrogans serovar Pomona appeared generally higher in 10 ewe lambs with fetal
      loss compared with 10 that were still pregnant. Histopathological investigation
      was not able to confirm that fetal loss was associated with leptospial infection.
      EPIDEMIOLOGICAL INVESTIGATION: In the 2012-born cohort of ewe lambs 443 were
      vaccinated with a bivalent leptospirosis vaccine and 882 unvaccinated. Serum was
      collected from 124 non-vaccinated ewe lambs between January and December 2013 for
      measurement of antibodies to Leptospira serovar Pomona and L. borgpetersenii
      serovar Hardjo-bovis using a microscopic agglutination test (MAT). Less than 5%
      of these ewe lambs were seropositive until May, but by August 85% and 48% of
      animals were seropositive to Leptospira serovars Hardjo-bovis and Pomona,
      respectively. Fetal loss in non-vaccinated ewe lambs was 78/882 (9%) compared
      with 23/443 (5%) in vaccinated ewe lambs. Combined data from the 2011- and 2012
      born ewe lambs (n=5,115) were analysed using a logistic regression model and
      fetal loss as the dependent variable. In the final model fetal loss was
      associated with pre-mating bodyweight (p=0.003), weight change from pre-mating to
      initial pregnancy diagnosis (p<0.001), year born and leptospirosis vaccination
      status (p=0.013). Amongst the serologically monitored ewe lambs, there were
      associations between fetal loss and being seropositive to Leptospira serovar
      Pomona using titre cut-points of 1:48 and 1:768 (p<0.001). CLINICAL RELEVANCE:
      Low pre-mating weight and/or low weight gain from mating to pregnancy diagnosis
      was associated with increased fetal loss, emphasising the importance of ewe lambs
      achieving target pre-mating weights and liveweight gains during pregnancy.
      Infection with Leptospira serovar Pomona was associated with fetal loss in the
      2012-born cohort and the possibility of infection with this serovar should be
      considered when investigating cases of fetal loss.

PMID- 25980524
TI  - Core information set for oesophageal cancer surgery.
AB  - BACKGROUND: Surgeons provide patients with information before surgery, although
      standards of information are lacking and practice varies. The development and use
      of a 'core information set' as baseline information before surgery may improve
      understanding. A core set is a minimum set of information to use in all
      consultations before a specific procedure. This study developed a core
      information set for oesophageal cancer surgery. METHODS: Information was
      identified from the literature, observations of clinical consultations and
      patient interviews. This was integrated to create a questionnaire survey.
      Stakeholders (patients and professionals) were surveyed twice to assess views on
      importance of information from 'not essential' to 'absolutely essential' using
      Delphi methods. Items not meeting predefined criteria were discarded after each
      survey and the final retained items were voted on, in separate patient and
      professional stakeholder meetings, to agree the core set. RESULTS: Some 67
      information items were identified initially from multiple sources. Survey
      response rates were 76.5 per cent (185 of 242) and 54.8 per cent (126 of 230) for
      patients and professionals respectively (first round), and over 83 per cent in
      both groups thereafter. Health professionals rated short-term clinical outcomes
      most highly (technical complications), whereas patients prioritized information
      related to long-term benefits. The consensus meetings agreed the final set, which
      consisted of: in-hospital milestones to recovery, rates of open-and-close
      surgery, in-hospital mortality, major complications (reoperation), milestones in
      recovery after discharge, longer-term eating and drinking and overall quality of
      life, and chances of survival. CONCLUSION: This study has established a core
      information set for surgery for oesophageal cancer.

PMID- 25980527
TI  - Influence of Centrally Mediated Symptoms on Postoperative Pain in Osteoarthritis
      Patients Undergoing Total Knee Arthroplasty: A Prospective Observational
      Evaluation.
AB  - BACKGROUND: Central sensitization plays an important role in the chronic pain
      experienced by osteoarthritis (OA) patients. In this prospective observational
      study, we investigated the influence of the level of preoperative centrally
      mediated symptoms measured by the Central Sensitization Inventory (CSI) on pain
      intensity after total knee arthroplasty (TKA) for OA. METHODS: Ninety-eight
      female OA patients undergoing TKA were enrolled in this study. We assessed CSI
      scores, pain-related data, and other clinical data preoperatively. All patients
      received spinal anesthesia and postoperative epidural analgesia. Pain intensity
      (at rest and on movement) and rescue meperidine requirements were assessed during
      postoperative days 1 and 2. Also, pain intensity and patient satisfaction were
      assessed 1 month and 3 months after surgery. After the completion of all
      postoperative assessments, we separated the study population into a preoperative
      CSI score >=40 and <40 group. We assessed pain-related data between the 2 groups
      at each assessment time. RESULTS: Ninety-one patients completed the postoperative
      assessments (a preoperative CSI >=40 group; n = 44, CSI <40 group; n = 47).
      Patients with preoperative CSI >=40 complained of a greater pain intensity (P =
      0.001) during postoperative days 1 and 2 and required a higher dose of meperidine
      rescue (P = 0.003) than those with a preoperative CSI <40. The high CSI score
      group also showed a less favorable outcome in terms of pain relief on follow-up
      at 1 month (P = 0.006) and 3 months (P = 0.002) after surgery. In multivariate
      analysis, a preoperative CSI score >=40 was the strongest determinant with 5.091
      of the highest odds ratio (95% CI 1.324 to 19.523, P = 0.016) for predicting a
      persistent pain 3 months after surgery among demographic and pain-related
      variables. CONCLUSIONS: OA patients with high levels of comorbid centrally
      mediated symptoms showed severe pain and increased analgesic requirements after
      TKA in the early postoperative period. Moreover, these patients seemed to be at
      higher risk of persistent pain, and a high CSI score was predictive of low
      patient satisfaction in terms of pain relief after surgery.

PMID- 25980528
TI  - Hierarchical Porous and High Surface Area Tubular Carbon as Dye Adsorbent and
      Capacitor Electrode.
AB  - Hierarchically porous tubular carbon (HPTC) with large surface area of 1094
      m(2)/g has been successfully synthesized by selectively removing lignin from
      natural wood. No templates or chemicals are involved during the process. By
      further KOH activation, surface area of activated HPTC reaches up to 2925 m(2)/g.
      These materials show unprecedented high adsorption capacity toward organic dyes
      (methylene blue, 838 mg/g; methyl orange, 264 mg/g) and large electrochemical
      capacitance of >200 F/g. The sustainable feature of the wood precursor and
      demonstrated superior adsorption and energy storage properties allow promising
      applications of the processed materials in energy and environmental related
      fields. 

PMID- 25980529
TI  - Elevated serum periostin is associated with liver stiffness and clinical outcome
      in biliary atresia.
AB  - OBJECTIVE: To analyze serum periostin and liver stiffness in postoperative
      biliary atresia (BA). METHODS: A total of 60 BA patients and 14 controls were
      enrolled. Serum periostin levels were analyzed by ELISA. Liver stiffness
      measurement was determined by transient elastography. RESULTS: Biliary atresia
      patients had significantly higher periostin and liver stiffness values than
      controls. Serum periostin levels were remarkably increased in BA patients with
      jaundice compared to those without jaundice. Moreover, serum periostin was
      correlated with liver stiffness. CONCLUSIONS: Serum periostin was associated with
      liver stiffness in BA. Thus, serum periostin has potential as a parameter
      reflecting the severity in BA.

PMID- 25980530
TI  - Wear behavior of pressable lithium disilicate glass ceramic.
AB  - This article reports effects of surface preparation and contact loads on abrasive
      wear properties of highly aesthetic and high-strength pressable lithium
      disilicate glass-ceramics (LDGC). Abrasive wear testing was performed using a pin
      on-disk device in which LDGC disks prepared with different surface finishes were
      against alumina pins at different contact loads. Coefficients of friction and
      wear volumes were measured as functions of initial surface finishes and contact
      loads. Wear-induced surface morphology changes in both LDGC disks and alumina
      pins were characterized using three-dimensional laser scanning microscopy,
      scanning electron microscopy, and energy dispersive X-ray spectroscopy. The
      results show that initial surface finishes of LDGC specimens and contact loads
      significantly affected the friction coefficients, wear volumes and wear-induced
      surface roughness changes of the material. Both wear volumes and friction
      coefficients of LDGC increased as the load increased while surface roughness
      effects were complicated. For rough LDGC surfaces, three-body wear was dominant
      while for fine LDGC surfaces, two-body abrasive wear played a key role.
      Delamination, plastic deformation, and brittle fracture were observed on worn
      LDGC surfaces. The adhesion of LDGC matrix materials to alumina pins was also
      discovered. This research has advanced our understanding of the abrasive wear
      behavior of LDGC and will provide guidelines for better utilization and
      preparation of the material for long-term success in dental restorations. (c)
      2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 968
      978, 2016.

PMID- 25980531
TI  - Synthesis and Coordination Chemistry of Iminophosphanes.
AB  - Iminophosphanes are a new group of 1,3-P,N-ligands, readily obtainable from
      secondary phosphanes and nitrilium ions, having a tunable N-donor site by means
      of varying the imine substituents. These ligands give, in high yields,
      monodentate gold complexes and bidentate rhodium and iridium complexes. Crystal
      structures are reported for both the ligands and the complexes. 

PMID- 25980532
TI  - Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling
      pathway.
AB  - Cerebrospinal fluid (CSF) includes conserved factors whose function is largely
      unexplored. To assess the role of CSF during embryonic development, CSF was
      repeatedly drained from embryonic zebrafish brain ventricles soon after their
      inflation. Removal of CSF increased cell death in the diencephalon, indicating a
      survival function. Factors within the CSF are required for neuroepithelial cell
      survival as injected mouse CSF but not artificial CSF could prevent cell death
      after CSF depletion. Mass spectrometry analysis of the CSF identified retinol
      binding protein 4 (Rbp4), which transports retinol, the precursor to retinoic
      acid (RA). Consistent with a role for Rbp4 in cell survival, inhibition of Rbp4
      or RA synthesis increased neuroepithelial cell death. Conversely, ventricle
      injection of exogenous human RBP4 plus retinol, or RA alone prevented cell death
      after CSF depletion. Zebrafish rbp4 is highly expressed in the yolk syncytial
      layer, suggesting Rbp4 protein and retinol/RA precursors can be transported into
      the CSF from the yolk. In accord with this suggestion, injection of human RBP4
      protein into the yolk prevents neuroepithelial cell death in rbp4 loss-of
      function embryos. Together, these data support the model that Rbp4 and RA
      precursors are present within the CSF and used for synthesis of RA, which
      promotes embryonic neuroepithelial survival.

PMID- 25980533
TI  - Heat shock protein 90: a pathophysiological factor and novel treatment target in
      autoimmune bullous skin diseases.
AB  - The chaperone heat shock protein 90 (Hsp90), a cell stress-inducible molecule
      that regulates activity of many client proteins responsible for cellular growth,
      differentiation and apoptosis, has been proposed as an important therapeutic
      target in patients with malignancies. More recently, its active participation in
      (auto)immune processes has been recognized as evidenced by amelioration of
      inflammatory disease pathways through pharmacological inhibition of Hsp90 in
      rodent models of autoimmune encephalomyelitis, rheumatoid arthritis and systemic
      lupus erythematosus. Based on own current research results, this viewpoint essay
      provides important insights that Hsp90 is also involved as a notable
      pathophysiological factor in autoimmune blistering dermatoses including
      epidermolysis bullosa acquisita, bullous pemphigoid and possibly dermatitis
      herpetiformis. The observed in vitro, ex vivo and in vivo efficacy of anti-Hsp90
      treatment in experimental models of autoimmune bullous diseases and its
      underlying multimodal anti-inflammatory mechanisms of interference with key
      contributors to autoimmune-mediated blister formation supports the introduction
      of selective non-toxic Hsp90 inhibitors into the clinical setting for the
      treatment of patients with these disorders.

PMID- 25980534
TI  - Actively targeted delivery of doxorubicin to bone metastases by a pH-sensitive
      conjugation.
AB  - Alendronate-monoethyl adipate-(hydrazone)-doxorubicin conjugate (ALN-MA-hyd-DOX)
      was synthesized to specifically deliver doxorubicin (DOX) to bone tumor tissue.
      The binding kinetics of ALN-MA-hyd-DOX with hydroxyapatite (HA) and natural bone
      were detected by using spectrophotometer. Cytotoxicity of ALN-MA-hyd-DOX on tumor
      cells was determined by MTT [3-(4,5-dimethylthiaol-2-yl)-2,5-diphenyl-tetrazolium
      bromide] method. The cellular uptake of ALN-MA-hyd-DOX was observed by using
      fluorescence microscopy. The in vivo antitumor activity of ALN-MA-hyd-DOX was
      investigated by using tumor-bearing nude mice model. The results indicated that
      ALN-MA-hyd-DOX was able to quickly bind with HA and natural bone. ALN-MA-hyd-DOX
      immobilized on the natural bone released more DOX in pH 5.0 medium than that in
      pH 6.0 or 7.4 medium. The cytotoxicity of ALN-MA-hyd-DOX toward A549 cells and
      MDA-MB-231/ADR cells was greater than DOX. ALN-MA-hyd-DOX was rapidly uptaken by
      A549 cells and MDA-MB-231/ADR cells. Compared with the same dose of free DOX, ALN
      MA-hyd-DOX significantly decreased tumor volume of tumor-bearing nude mice. DOX
      mainly distributed in bone tumor tissue after ALN-MA-hyd-DOX was intravenously
      administered to tumor-bearing nude mice, whereas DOX distributed through the
      whole body after DOX was intravenously administered to tumor-bearing nude mice.
      These findings implied that the ALN-MA-hyd-DOX was a promising bone-targeted
      conjugate for treating bone neoplasms.

PMID- 25980540
TI  - The working mechanism of the beta-carbonic anhydrase degrading carbonyl sulphide
      (COSase): a theoretical study.
AB  - In order to give insights into the working mechanism of the novel characterized
      enzyme carbonyl sulphide hydrolase (COSase), which efficiently converts COS into
      H2S and CO2, we have performed a detailed theoretical investigation using the
      framework of density functional theory (using B3LYP and M06 exchange-correlation
      functionals) by the cluster model approach. In the final part of the reaction the
      metal ion is unable to form a pentacoordinated species. The B3LYP-D3 and M06
      potential energy surfaces have a very similar shape. The elucidation of the
      catalytic reduction of COS is important in view of its role in environmental
      chemistry. 

PMID- 25980541
TI  - The Significance of Ion Conduction in a Hybrid Organic-Inorganic Lead-Iodide
      Based Perovskite Photosensitizer.
AB  - The success of perovskite solar cells has sparked enormous excitement in the
      photovoltaic community not only because of unexpectedly high efficiencies but
      also because of the future potential ascribed to such crystalline absorber
      materials. Far from being exhaustively studied in terms of solid-state
      properties, these materials surprised by anomalies such as a huge apparent low
      frequency dielectric constant and pronounced hysteretic current-voltage behavior.
      Here we show that methylammonium (but also formamidinium) iodoplumbates are mixed
      conductors with a large fraction of ion conduction because of iodine ions. In
      particular, we measure and model the stoichiometric polarization caused by the
      mixed conduction and demonstrate that the above anomalies can be explained by the
      build-up of stoichiometric gradients as a consequence of ion blocking interfaces.
      These findings provide insight into electrical charge transport in the hybrid
      organic-inorganic lead halide solar cells as well as into new possibilities of
      improving the photovoltaic performance by controlling the ionic disorder. 

PMID- 25980542
TI  - Characterization of Antibodies and Development of an Indirect Competitive
      Immunoassay for Detection of Deamidated Gluten.
AB  - Diversification of gluten applications in the food and cosmetics industries was
      achieved through the production of water-soluble gluten that can be obtained by
      deamidation. Current analytical methods dedicated to gluten detection failed to
      detect deamidated gluten. After immunizing mice with the peptide LQPEEPFPE
      conjugated to keyhole limpet hemocyanin, five mouse monoclonal antibodies (mAbs)
      were produced and sequences of bound epitopes were determined as XPXEPFPE, where
      X is Q or E. The mAbs exhibited high specificity for deamidated gliadins and low
      molecular weight glutenin subunits. A competitive enzyme-linked immunosorbent
      assay (ELISA) based on INRA-DG1 mAb was developed with an IC50% of 85 ng/mL and a
      limit of detection of 25 ng/mL. The intra- and interassay coefficients of
      variation (CV) were <10% except for the interassay CV of the low-level control
      (40 ng/mL), which was 20%. This assay was capable of detecting three of the four
      deamidated gluten samples spiked in rice flour at 20 mg/kg. 

PMID- 25980544
TI  - [Not Available].

PMID- 25980543
TI  - Erythema annulare centrifugum-like mycosis fungoides after unrelated bone marrow
      transplantation.

PMID- 25980545
TI  - Monte Carlo Simulation of Characteristic Secondary Fluorescence in Electron Probe
      Microanalysis of Homogeneous Samples Using the Splitting Technique.
AB  - Electron probe microanalysis (EPMA) is based on the comparison of characteristic
      intensities induced by monoenergetic electrons. When the electron beam ionizes
      inner atomic shells and these ionizations cause the emission of characteristic X
      rays, secondary fluorescence can occur, originating from ionizations induced by X
      ray photons produced by the primary electron interactions. As detectors are
      unable to distinguish the origin of these characteristic X-rays, Monte Carlo
      simulation of radiation transport becomes a determinant tool in the study of this
      fluorescence enhancement. In this work, characteristic secondary fluorescence
      enhancement in EPMA has been studied by using the splitting routines offered by
      PENELOPE 2008 as a variance reduction alternative. This approach is controlled by
      a single parameter NSPLIT, which represents the desired number of X-ray photon
      replicas. The dependence of the uncertainties associated with secondary
      intensities on NSPLIT was studied as a function of the accelerating voltage and
      the sample composition in a simple binary alloy in which this effect becomes
      relevant. The achieved efficiencies for the simulated secondary intensities bear
      a remarkable improvement when increasing the NSPLIT parameter; although in most
      cases an NSPLIT value of 100 is sufficient, some less likely enhancements may
      require stronger splitting in order to increase the efficiency associated with
      the simulation of secondary intensities. 

PMID- 25980546
TI  - A2a and a2b adenosine receptors affect HIF-1alpha signaling in activated primary
      microglial cells.
AB  - Microglia are central nervous system (CNS)-resident immune cells, that play a
      crucial role in neuroinflammation. Hypoxia-inducible factor-1 (HIF-1), the main
      transcription factor of hypoxia-inducible genes, is also involved in the immune
      response, being regulated in normoxia by inflammatory mediators. Adenosine is an
      ubiquitous nucleoside that has an influence on many immune properties of
      microglia through interaction with four receptor subtypes. The aim of this study
      was to investigate whether adenosine may affect microglia functions by acting on
      HIF-1alpha modulation. Primary murine microglia were activated with
      lipopolysaccharide (LPS) with or without adenosine, adenosine receptor agonists
      and antagonists and HIF-1alpha accumulation and downstream genes regulation were
      determined. Adenosine increased LPS-induced HIF-1alpha accumulation leading to an
      increase in HIF-1alpha target genes involved in cell metabolism [glucose
      transporter-1 (GLUT-1)] and pathogens killing [inducible nitric-oxide synthase
      (iNOS)] but did not induce HIF-1alpha dependent genes related to angiogenesis
      [vascular endothelial growth factor (VEGF)] and inflammation [tumor necrosis
      factor-alpha (TNF-alpha)]. The stimulatory effect of adenosine on HIF-1alpha and
      its target genes was essentially exerted by activation of A2A through p44/42 and
      A2B subtypes via p38 mitogen-activated protein kinases (MAPKs) and Akt
      phosphorylation. Furthermore the nucleoside raised VEGF and decreased TNF-alpha
      levels, by activating A2B subtypes. In conclusion adenosine increases GLUT-1 and
      iNOS gene expression in a HIF-1alpha-dependent way, through A2A and A2B
      receptors, suggesting their role in the regulation of microglial cells function
      following injury. However, inhibition of TNF-alpha adds an important anti
      inflammatory effect only for the A2B subtype. GLIA 2015;63:1933-1952.

PMID- 25980547
TI  - High-throughput cell-cycle imaging opens new doors for discovery.
AB  - During the life of a cell, numerous essential cellular processes must be
      coordinated both spatially and temporally, from DNA replication and chromosome
      segregation to gene expression and cytokinesis. In order to analyze these
      inherently dynamic and cell-cycle-dependent processes, it is essential to observe
      the dynamic localization of the cellular machinery throughout the entire cell
      cycle. Although some coarse features of cell-cycle dynamics can be captured in
      snapshot imaging, where cellular size or morphology can be used as a proxy for
      cell-cycle phase, the inherently stochastic nature of ultrastructures in the cell
      makes the direct visualization of subcellular dynamics an essential tool to
      differentiate between structural differences that are the result of biologically
      relevant dynamics versus cell-to-cell variation. With these goals in mind, we
      have developed a unique high-throughput imaging approach, and have recently
      applied this to characterize the cell-cycle localization of nearly every protein
      in the bacterial cell (Kuwada in Mol Microbiol, 95(1), 64-79, 2015). This
      approach combines large-format sample preparation with automated image capture,
      processing, and analysis to quantitatively characterize proteome localization of
      tens of thousands of complete cell cycles. 

PMID- 25980548
TI  - Modulation of Igbeta is essential for the B cell selection in germinal center.
AB  - The positive and negative selection of antigen-reactive B cells take place in the
      germinal center (GC) during an immune responses. However, the precise molecular
      mechanisms underlying these selection machineries, including the involvement of
      antigen receptor signaling molecules, remain to be elucidated. We found that
      expression levels of Igalpha and Igbeta, which are the essential components of B
      cell antigen-receptor complex, were differentially regulated in GC B cells and
      that the expression of Igbeta was more prominently down-regulated in a portion of
      GC B cells. The suppression of Igbeta down-regulation reduced the number of
      GL7(+)GC B cells and the affinity maturation in T-dependent responses was
      markedly impaired. In addition, the disease phenotypes in autoimmune-prone mice
      were ameliorated by blocking of Igbeta down-regulation. These results suggest
      that Igbeta down-regulation is involved in the normal positive selection in GC
      and the accumulation of autoreactive B cells in autoimmune-prone mice. 

PMID- 25980549
TI  - Wear of tooth enamel against silver-palladium-gold alloy and two other
      restorative materials in vitro.

PMID- 25980550
TI  - High-fidelity in simulation education: Only a part of the answer.

PMID- 25980551
TI  - Impacts of parturition and body condition score on glucose uptake capacity of
      bovine monocyte subsets.
AB  - The peripartal period of dairy cows is associated with a higher incidence of
      infectious diseases like mastitis or metritis, particularly in high-yielding
      animals. The onset of lactation induces a negative energy balance and a shift of
      glucose distribution toward the udder. Glucose is used as primary fuel by
      monocytes which give rise to macrophages, key cells in the defense against
      pathogens. The aim of this study was to analyze whether animals with high or low
      body condition score (BCS) differ in composition and glucose uptake capacities of
      bovine monocyte subsets. Blood samples were taken from 27 dairy cows starting 42
      days before parturition until day 56 after parturition. The cows were allocated
      to two groups according to their BCS. A feeding regime was applied, in which the
      BCS high group received higher amounts of concentrate before parturition and
      concentrate feeding was more restricted in the BCS high group after parturition
      compared with the BCS low group, to promote postpartal lipolysis and enhance
      negative energy balance in the BCS high group. Blood cell counts of classical
      (cM), intermediate (intM) and nonclassical monocytes (ncM) were increased at day
      7 after calving. In the BCS low group intM numbers were significantly higher
      compared to the BCS high group at day 7 after parturition. Within the BCS low
      group cows suffering from mastitis or metritis showed significantly higher
      numbers of cM, intM and ncM at day 7 after parturition. Classical monocytes and
      intM showed similar glucose uptake capacities while values for ncM were
      significantly lower. Compared with antepartal capacities and irrespective of BCS
      and postpartal mastitis or metritis, glucose uptake of all monocyte subsets
      decreased after parturition. In conclusion, whereas glucose uptake capacity of
      bovine monocyte subsets is altered by parturition, it is not linked to the energy
      supply of the animals or to postpartal infectious diseases. 

PMID- 25980552
TI  - Changes in energy during treatment of depression: an analysis of duloxetine in
      double-blind placebo-controlled trials.
AB  - AIMS: The aim of this study was to assess how quickly and effectively duloxetine
      improves energy compared with placebo in patients with major depressive disorder
      (MDD). METHODS: Data from 10 randomised, double-blind, placebo-controlled
      clinical trials examining duloxetine (40-60 mg/day) vs. placebo in patients
      diagnosed with MDD were analysed. Change from baseline at Week 1 through Week 8
      in Hamilton Depression Rating Scale (HAM-D) retardation subscale score (Item 1 -
      depressed mood, Item 7 - work and activities, Item 8 - retardation and Item 14 -
      genital symptoms) was assessed with mixed model repeated measures analysis.
      Positive predictive values and negative predictive values were calculated for
      predictor analysis. RESULTS: Patients treated with duloxetine (N = 1522)
      experienced statistically significantly (p <= 0.05) greater reductions in HAM-D
      retardation subscale scores vs. placebo (N = 1180) starting at Week 1 throughout
      Week 8 of treatment. Of the patients with early energy improvement (>= 20%
      reduction in HAM-D retardation subscale scores) at Week 1, 48% achieved remission
      (HAM-D total score <= 7) at Week 8; 48% and 46% of patients who experienced early
      energy improvement at Weeks 2 and 4, respectively, achieved remission at Week 8.
      DISCUSSION: We demonstrated that treatment with duloxetine, quickly and with
      increasing magnitude over treatment time, improves low energy symptoms. As early
      as 1 week after starting treatment with duloxetine, improvement of low energy may
      serve as a predictor of remission at end-point. CONCLUSIONS: Treatment with
      duloxetine improves energy in patients with MDD and early response in retardation
      may serve as a modest predictor of remission at end-point. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.gov. Study Identifiers: NCT00036335; NCT00073411;
      NCT00406848 and NCT00536471. Studies HMAQa, HMAQb, HMATa, HMATb, HMBHa and HMBHb
      predate the registration requirement. DATA POSTING: ClinicalTrials.gov. Study
      Identifiers: NCT00406848; NCT00536471.

PMID- 25980553
TI  - Preparing to prescribe: How do clerkship students learn in the midst of
      complexity?
AB  - Prescribing tasks, which involve pharmacological knowledge, clinical decision
      making and practical skill, take place within unpredictable social environments
      and involve interactions within and between endlessly changing health care teams.
      Despite this, curriculum designers commonly assume them to be simple to learn and
      perform. This research used mixed methods to explore how undergraduate medical
      students learn to prescribe in the 'real world'. It was informed by cognitive
      psychology, sociocultural theory, and systems thinking. We found that learning to
      prescribe occurs as a dynamic series of socially negotiated interactions within
      and between individuals, communities and environments. As well as a thematic
      analysis, we developed a framework of three conceptual spaces in which learning
      opportunities for prescribing occur. This illustrates a complex systems view of
      prescribing education and defines three major system components: the "social
      space", where the environmental conditions influence or bring about a learning
      experience; the "process space", describing what happens during the learning
      experience; and the intra-personal "cognitive space", where the learner may
      develop aspects of prescribing expertise. This conceptualisation broadens the
      scope of inquiry of prescribing education research by highlighting the complex
      interplay between individual and social dimensions of learning. This perspective
      is also likely to be relevant to students' learning of other clinical
      competencies. 

PMID- 25980554
TI  - Observation of the internal response of the kidney during compressive loading
      using ultrafast ultrasonography.
AB  - A protocol based on ultrafast ultrasonography was developed to study the internal
      response of isolated perfused human (n=3) and porcine (n=11) kidneys subjected to
      loading at 0.003 m/s and 0.3m/s respectively. Regional uniaxial strains were
      calculated based on natural target tracking. The effect of loading speed and
      regional differences could be statistically detected on the porcine specimens.
      However, despite the inhomogeneity of their anatomical structures, strains'
      responses appeared relatively homogeneous at 0.3m/s in both porcine and human
      kidneys. Failure, identified as a sudden change on the ultrasonography movie,
      also appeared at similar compression levels for both species (38.3% of applied
      strain in average for human and 35.8% of applied strain in average for porcine).

PMID- 25980555
TI  - Non-invasive in vivo time-dependent strain measurement method in human abdominal
      aortic aneurysms: Towards a novel approach to rupture risk estimation.
AB  - We aim to introduce a novel, inverse method for in vivo material parameter
      identification of human abdominal aortic aneurysms (AAA), which could overcome
      one of the greatest sources of uncertainty in patient-specific simulations, and
      could also serve as a rapid, patient-calibrated, novel measure of aneurysm
      rupture risk. As an initial step, the determination of the kinematic fields is
      presented here. Images of the AAA lumen, acquired in 10 discrete time-steps
      through a stabilized cardiac cycle by electrocardiogram-gated computer tomography
      angiography, are used to approximate the in vivo, time dependent kinematic fields
      of the arterial wall using a novel, incompressible Kirchhoff-Love shell element
      implemented into the isogeometric analysis framework. Defining a smoothing
      parametric surface via 2D bicubic spline fitting in the spatial, and by harmonic
      regression in the temporal domain, we are able to adequately mitigate the
      measurement inaccuracy. The ill-posedness of the problem requires certain
      assumptions on the displacement. In our case, based on numerical fluid structure
      interaction simulation observations, we hypothesized the incremental displacement
      vector of the reference surface to coincide with its corrected normal; hence the
      periodic movement was assured. Finally, we present two examples: an AAA and an
      undilated calcificated aorta. Strains in the diseased part were compared to those
      in a healthy arterial section of the same patient and found to have significant
      differences in both specimens. In the case of AAAs, high spatial gradients
      surrounding the dilated part indicate abrupt changes in material properties, a
      phenomenon less significant for the atherosclerotic case. 

PMID- 25980556
TI  - Prediction of contact mechanics in metal-on-metal Total Hip Replacement for
      parametrically comprehensive designs and loads.
AB  - Manufacturers and investigators of Total Hip Replacement (THR) bearings require
      tools to predict the contact mechanics resulting from diverse design and loading
      parameters. This study provides contact mechanics solutions for metal-on-metal
      (MoM) bearings that encompass the current design space and could aid pre-clinical
      design optimization and evaluation. Stochastic finite element (FE) simulation was
      used to calculate the head-on-cup contact mechanics for five thousand
      combinations of design and loading parameters. FE results were used to train a
      Random Forest (RF) surrogate model to rapidly predict the contact patch
      dimensions, contact area, pressures and plastic deformations for arbitrary
      designs and loading. In addition to widely observed polar and edge contact, FE
      results included ring-polar, asymmetric-polar, and transitional categories which
      have previously received limited attention. Combinations of design and load
      parameters associated with each contact category were identified. Polar contact
      pressures were predicted in the range of 0-200 MPa with no permanent deformation.
      Edge loading (with subluxation) was associated with pressures greater than 500
      MPa and induced permanent deformation in 83% of cases. Transitional-edge contact
      (with little subluxation) was associated with intermediate pressures and
      permanent deformation in most cases, indicating that, even with ideal anatomical
      alignment, bearings may face extreme wear challenges. Surrogate models were able
      to accurately predict contact mechanics 18,000 times faster than FE analyses. The
      developed surrogate models enable rapid prediction of MoM bearing contact
      mechanics across the most comprehensive range of loading and designs to date, and
      may be useful to those performing bearing design optimization or evaluation.

PMID- 25980557
TI  - Exploring the high-dimensional structure of muscle redundancy via subject
      specific and generic musculoskeletal models.
AB  - Subject-specific and generic musculoskeletal models are the computational
      instantiation of hypotheses, and stochastic techniques help explore their
      validity. We present two such examples to explore the hypothesis of muscle
      redundancy. The first addresses the effect of anatomical variability on static
      force capabilities for three individual cat hindlimbs, each with seven kinematic
      degrees of freedom (DoFs) and 31 muscles. We present novel methods to
      characterize the structure of the 31-dimensional set of feasible muscle
      activations for static force production in every 3-D direction. We find that task
      requirements strongly define the set of feasible muscle activations and limb
      forces, with few differences comparing individual vs. species-average results.
      Moreover, muscle activity is not smoothly distributed across 3-D directions. The
      second example explores parameter uncertainty during a flying disc throwing
      motion by using a generic human arm with five DoFs and 17 muscles to predict
      muscle fiber velocities. We show that the measured joint kinematics fully
      constrain the eccentric and concentric fiber velocities of all muscles via their
      moment arms. Thus muscle activation for limb movements is likely not redundant:
      there is little, if any, latitude in synchronizing alpha-gamma motoneuron
      excitation-inhibition for muscles to adhere to the time-critical fiber velocities
      dictated by joint kinematics. Importantly, several muscles inevitably exhibit
      fiber velocities higher than thought tenable, even for conservative throwing
      speeds. These techniques and results, respectively, enable and compel us to
      continue to revise the classical notion of muscle redundancy for increasingly
      more realistic models and tasks. 

PMID- 25980558
TI  - Challenges in achieving patient participation: A review of how patient
      participation is addressed in empirical studies.
AB  - BACKGROUND: For decades, it has been an ideal in western countries that
      individuals should participate in society as self-governing and autonomous
      subjects; however, this ideal does not always correspond to the actual
      experiences of individuals in their encounters with health professionals. AIM:
      This review identifies how empirical studies address challenges in achieving
      patient participation in clinical nursing. METHOD: We conducted a literature
      search for studies of patient participation in PubMed, Cinahl, PsychInfo and
      Scopus. In a systematic review using Garrard's matrix method, we selected
      empirical studies that focused on patients' participation in health services.
      MAIN FINDINGS: The empirical studies we investigated addressed the relationship
      between patient and nurse, knowledge, contact time with the patient, severity of
      illness and the effect of age on the degree of patient involvement. Every study
      thus investigated assessed patient participation as being achievable. None of the
      studies questioned the foundation for patient participation, which has been
      described in theoretical articles. The main explanation for difficulties in
      achieving patient participation was that expectations concerning the extent and
      quality of participation could be unrealistic and lead to dissatisfaction.
      CONCLUSIONS: Studies on patient participation identify challenges due to the
      nature of the relationship between laypersons and professionals, and the embedded
      difference in situation and knowledge. This difference may be reduced by time and
      a mutually positive attitude. But participation in its ideal form cannot be
      achieved because of this fundamental difference. Therefore, the optimal level of
      patient participation can only be achieved within a framework which provides both
      patients and health professionals with adequate time to build relationships and
      shared knowledge.

PMID- 25980559
TI  - Bioaccessibility of heavy metals in soils cannot be predicted by a single model
      in two adjacent areas.
AB  - The objective of this study was to examine whether a single model could be used
      to predict the bioaccessibility of heavy metals in soils in two adjacent areas
      and to determine the feasibility of using existing data sets of total metal
      concentrations and soil property parameters (e.g., pH, total organic carbon, and
      soil texture) when predicting heavy metal bioaccessibility. A total of 103
      topsoil samples were collected from two adjacent areas (Baotou and Bayan Obo). A
      total of 76 samples were collected from Baotou, and 27 were collected from Bayan
      Obo. The total and bioaccessible concentrations of arsenic (As), copper (Cu),
      lead (Pb), and zinc (Zn) were measured following complete composite acid
      digestion and a simple bioaccessibility extraction test. The average total
      concentrations of As, Cu, Pb, and Zn were 8.95, 27.53, 28.40, and 79.50 mg/kg,
      respectively, in Baotou and 18.12, 30.75, 38.09, and 87.62 mg/kg in Bayan Obo.
      Except for As, these values were similar in both areas. The average bioaccessible
      heavy metal concentrations (Bio-HMs) for each target HM were also similar. In
      Baotou, the average Bio-HM values for As, Cu, Pb, and Zn were 1.16, 3.76, 16.31,
      and 16.10 mg/kg, respectively, and 1.26, 2.51, 14.31, and 8.68 mg/kg in Bayan
      Obo. However, the relative bioaccessibilities for each HM in Baotou were greater
      than those in Bayan Obo, with mean values for Pb, Zn, Cu, and As of 57, 20, 17,
      and 12 %, respectively, in Baotou and 40, 11, 9, and 8 % in Bayan Obo. In both
      areas, prediction models were successfully created using heavy metal
      concentrations and soil physicochemical parameters; however, models of the same
      target element differed between the areas, which indicated that a common model
      for both sites does not exist. Bio-HMs were highly affected by soil properties,
      which were found to differ between the adjacent areas. In addition, soil
      properties with large variations played major roles in the predictive models.
      This study highlights the importance of incorporating physical and chemical
      parameters that vary greatly when building predictive models of heavy metal
      bioaccessibility in soil. A similarity in soil properties between areas might be
      a prerequisite for the creation of a common predictive model for soil Bio-HMs. 

PMID- 25980560
TI  - Impact of biochar produced from post-harvest residue on the adsorption behavior
      of diesel oil on loess soil.
AB  - The primary objective of this study was to investigate the effect of biochar,
      produced from wheat residue at different temperatures, on the adsorption of
      diesel oil by loess soil. Kinetic and equilibrium data were processed to
      understand the adsorption mechanism of diesel by biochar-affected loess soil;
      dynamic and thermodynamic adsorption experiments were conducted to characterize
      this adsorption. The surface features and chemical structure of biochar, modified
      at varying pyrolytic temperatures, were investigated using surface scanning
      electron microscopy and Fourier transform infrared analysis. The kinetic data
      showed that the adsorption of diesel oil onto loess soil could be described by a
      pseudo-second-order kinetic model, with the rate-controlling step being
      intraparticle diffusion. However, in the presence of biochar, boundary layer
      control and intraparticle diffusion were both involved in the adsorption.
      Besides, the adsorption equilibrium data were well described by the Freundlich
      isothermal model. The saturated adsorption capacity weakened as temperature
      increased, suggesting a spontaneous exothermic process. Thermodynamic parameter
      analysis showed that adsorption was mainly a physical process and was enhanced by
      chemical adsorption. The adsorption capacity of loess soil for diesel oil was
      weakened with increasing pH. The biochar produced by pyrolytic wheat residue
      increased the adsorption behavior of petroleum pollutants in loess soil. 

PMID- 25980561
TI  - Clinical and economic burden of community-acquired pneumonia in the Veterans
      Health Administration, 2011: a retrospective cohort study.
AB  - PURPOSE: The burden of community-acquired pneumonia (CAP) is not well described
      in the US Veterans Health Administration (VHA). METHODS: CAP was defined as
      having a pneumonia diagnosis with evidence of chest X-ray, and no evidence of
      prior (90 days) hospitalization/long-term care. We calculated incidence rates of
      adult CAP occurring in inpatient or outpatient VHA settings in 2011. We also
      estimated the proportion of VHA CAP patients who were hospitalized, were
      readmitted within 30 days of hospital discharge, and died (any cause) in the year
      following diagnosis. Incremental costs during the 90 days following a CAP
      diagnosis were estimated from the perspective of the VHA. RESULTS: In 2011,
      34,101 Veterans developed CAP (35,380 episodes) over 7,739,757 VHA person-years.
      Median age of CAP patients was 65 years (95 % male). CAP incidence rates were
      higher for those aged >=50 years. A majority of Veterans aged 50-64 (53 %) and
      >=65 (66 %) years had >=1 chronic medical (moderate risk) or immunocompromising
      (high risk) condition. Compared to those at low-risk (healthy), moderate- and
      high-risk Veterans were >3 and >6 times more likely to develop CAP, respectively.
      The percentage of CAP patients who were hospitalized was 45 %, ranging from 12 %
      (age 18-49, low risk) to 57 % (age >=65, high risk). One-year all-cause mortality
      rates ranged from 1 % (age 18-49, low risk) to 36 % (age >=65, high risk). Annual
      VHA medical expenditure related to CAP was estimated to be $750 million (M)
      ($415M for those aged >=65 years). CONCLUSION: A focus on CAP prevention among
      older Veterans and those with comorbid or immunocompromising conditions is
      important.

PMID- 25980563
TI  - Turbulence, Temperature, and Turbidity: The Ecomechanics of Predator-Prey
      Interactions in Fishes.
AB  - Successful feeding and escape behaviors in fishes emerge from precise integration
      of locomotion and feeding movements. Fishes inhabit a wide range of habitats,
      including still ponds, turbulent rivers, and wave-pounded shorelines, and these
      habitats vary in several physical variables that can strongly impact both
      predator and prey. Temperature, the conditions of ambient flow, and light regimes
      all have the potential to affect predator-prey encounters, yet the integration of
      these factors into our understanding of fish biomechanics is presently limited.
      We explore existing knowledge of kinematics, muscle function, hydrodynamics, and
      evolutionary morphology in order to generate a framework for understanding the
      ecomechanics of predator-prey encounters in fishes. We expect that, in the
      absence of behavioral compensation, a decrease in temperature below the optimum
      value will reduce the muscle power available both to predator and prey, thus
      compromising locomotor performance, suction-feeding mechanics of predators, and
      the escape responses of prey. Ambient flow, particularly turbulent flow, will
      also challenge predator and prey, perhaps resulting in faster attacks by
      predators to minimize mechanical instability, and a reduced responsiveness of
      prey to predator-generated flow. Reductions in visibility, caused by depth,
      turbidity, or diel fluctuations in light, will decrease distances at which either
      predator or prey detect each other, and generally place a greater emphasis on the
      role of mechanoreception both for predator and prey. We expect attack distances
      to be shortened when visibility is low. Ultimately, the variation in abiotic
      features of a fish's environment will affect locomotion and feeding performance
      of predators, and the ability of the prey to escape. The nature of these effects
      and how they impact predator-prey encounters stands as a major challenge for
      future students of the biomechanics of fish during feeding. Just as fishes show
      adaptations for capturing specific types of prey, we anticipate they are also
      adapted to the physical features of their preferred habitat and show a myriad of
      behavioral mechanisms for dealing with abiotic factors during predator-prey
      encounters. 

PMID- 25980564
TI  - Using Technology to Expand the Classroom in Time, Space, and Diversity.
AB  - Diverse classrooms offer distinct advantages over homogeneous classrooms, for
      example by providing a greater diversity of perspectives and opportunities.
      However, there is substantial underrepresentation of numerous groups throughout
      science, technology, engineering, and mathematics (STEM) education, from
      secondary schools through professional ranks and academia. In this piece I offer
      a critical analysis of three worked examples of how technology can be used to
      expand traditional definitions of the classroom environment. In doing so I show
      how technology can be used to help make STEM classrooms more expansive,
      equitable, and effective learning environments. First I highlight how peer-to
      peer learning was used to foster knowledge of marine conservation with high
      school youth across Fiji and Chicago. Second I show how social media can be used
      to facilitate conversations in New York City after a natural disaster. Finally, I
      show how integrating digital and real-world learning can help a diverse group of
      students from the Pacific islands gain field-based STEM techniques in an extended
      workshop format. Taken together these examples show how digital technology could
      expand the fixed walls of the academy and that technology can help show students
      the vivid splendor of life outside the classroom. 

PMID- 25980562
TI  - Rapid Effects of Estradiol on Aggression in Birds and Mice: The Fast and the
      Furious.
AB  - Across invertebrates and vertebrates, steroids are potent signaling molecules
      that affect nearly every cell in the organism, including cells of the nervous
      system. Historically, researchers have focused on the genomic (or "nuclear
      initiated") effects of steroids. However, all classes of steroids also have rapid
      non-genomic (or "membrane-initiated") effects, although there is far less basic
      knowledge of these non-genomic effects. In particular, steroids synthesized in
      the brain ("neurosteroids") have genomic and non-genomic effects on behavior.
      Here, we review evidence that estradiol has rapid effects on aggression, an
      important social behavior, and on intracellular signaling cascades in relevant
      regions of the brain. In particular, we focus on studies of song sparrows
      (Melospiza melodia) and Peromyscus mice, in which estradiol has rapid behavioral
      effects under short photoperiods only. Furthermore, in captive Peromyscus,
      estrogenic compounds (THF-diols) in corncob bedding profoundly alter the rapid
      effects of estradiol. Environmental factors in the laboratory, such as
      photoperiod, diet, and bedding, are critical variables to consider in
      experimental design. These studies are consistent with the hypothesis that
      locally-produced steroids are more likely than systemic steroids to act via non
      genomic mechanisms. Furthermore, these studies illustrate the dynamic balance
      between genomic and non-genomic signaling for estradiol, which is likely to be
      relevant for other steroids, behaviors, and species. 

PMID- 25980565
TI  - The Need for Speed: Neuroendocrine Regulation of Socially-controlled Sex Change.
AB  - Socially-controlled functional sex change in fishes is a dramatic example of
      adaptive reproductive plasticity. Functional gonadal sex change can occur within
      a week while behavioral sex change can begin within minutes. Significant progress
      has been made in understanding the neuroendocrine bases of this phenomenon at
      both the gonadal and the neurobiological levels, but a detailed mechanistic
      understanding remains elusive. We are working with sex-changing wrasses to
      identify evolutionarily-conserved neuroendocrine pathways underlying this
      reproductive adaptation. One key model is the bluehead wrasse (Thalassoma
      bifasciatum), in which sex change is well studied at the behavioral, ecological,
      and neuroendocrine levels. Bluehead wrasses show rapid increases in aggressive
      and courtship behaviors with sex change that do not depend on the presence of
      gonads. The display of male-typical behavior is correlated with the expression of
      arginine vasotocin, and experiments support a role for this neuropeptide.
      Estrogen synthesis is also critical in the process. Female bluehead wrasses have
      higher abundance of aromatase mRNA in the brain and gonads, and estrogen implants
      block behavioral sex change. While established methods have advanced our
      understanding of sex change, a full understanding will require new approaches and
      perspectives. First, contributions of other neuroendocrine systems should be
      better characterized, particularly glucocorticoid and thyroid signaling. Second,
      advances in genomics for non-traditional model species should allow conserved
      mechanisms to be identified with a key next-step being manipulative tests of
      these mechanisms. Finally, advances in genomics now also allow study of the role
      of epigenetic modifications and other regulatory mechanisms in the dramatic
      alterations across the sex-change process. 

PMID- 25980566
TI  - Suction, Ram, and Biting: Deviations and Limitations to the Capture of Aquatic
      Prey.
AB  - When feeding, most aquatic organisms generate suction that draws prey into the
      mouth. The papers in this volume are a demonstration of this fact. However, under
      what circumstances is suction ineffective as a feeding mechanism? Here we
      consider the interplay between suction, ram, and biting, and analyze the
      contribution of each to the capture of prey by a wide variety of species of fish.
      We find, not surprisingly, that ram is the dominant contributor to feeding
      because suction, and biting, are only effective when very close to the prey. As
      species utilize more strongly ram-dominated modes of feeding, they may be
      released from the morphological and behavioral constraints associated with the
      need to direct a current of water into the head. Morphological and behavioral
      changes that facilitate larger gapes and stronger jaws are explored here,
      including predators that lack a protrusile upper jaw, predators with elongate
      jaws, predators that rely on suspension feeding, and predators that bite.
      Interestingly, while the mobility of the jaws and the shape of the opening of the
      mouth are modified in species that have departed from a primary reliance on
      suction feeding, the anterior-to-posterior wave of expansion persists. This wave
      may be greatly slowed in ram and biting species, but its retention suggests a
      fundamental importance to aquatic feeding. 

PMID- 25980567
TI  - Environmental Change, the Stress Response, and Neurogenesis.
AB  - Previous to the 1980's, the prevailing neuroscience dogma held that no new
      neurons were produced in the brains of adult mammals. Now, we understand that the
      production of new neurons, or neurogenesis, is a common and plastic process in
      the adult brain. To date, however, researchers have not come to a unified
      understanding of the functional significance of neurogenesis. Several factors
      have been shown to modulate hippocampal neurogenesis including spatial learning,
      stress, and aspects of environmental change, but questions still remain. How do
      these modulating factors overlap? Which aspects of environmental change induce a
      stress response? Is there a relationship between hippocampal neurogenesis, the
      stress response, and environmental change? Can this relationship be altered when
      taking into consideration other factors such as perception and predictability of
      the environment? Finally, do results from neurobiological research on laboratory
      rodents translate to wild systems? This review attempts to address these
      questions and synthesize research from the fields of ecology, psychology, and
      behavioral neuroscience. 

PMID- 25980568
TI  - Morphology, Kinematics, and Dynamics: The Mechanics of Suction Feeding in Fishes.
AB  - Suction feeding is pervasive among aquatic vertebrates, and our understanding of
      the functional morphology and biomechanics of suction feeding has recently been
      advanced by combining experimental and modeling approaches. Key advances include
      the visualization of the patterns of flow in front of the mouth of a feeding
      fish, the measurement of pressure inside their mouth cavity, and the employment
      of analytical and computational models. Here, we review the key components of the
      morphology and kinematics of the suction-feeding system of anatomically
      generalized, adult ray-finned fishes, followed by an overview of the
      hydrodynamics involved. In the suction-feeding apparatus, a strong mechanistic
      link among morphology, kinematics, and the capture of prey is manifested through
      the hydrodynamic interactions between the suction flows and solid surfaces (the
      mouth cavity and the prey). It is therefore a powerful experimental system in
      which the ecology and evolution of the capture of prey can be studied based on
      first principals. 

PMID- 25980569
TI  - Modeling Optimal Strategies for Finding a Resource-Linked, Windborne Odor Plume:
      Theories, Robotics, and Biomimetic Lessons from Flying Insects.
AB  - Male moths locate females by navigating along her pheromone plume, often flying
      hundreds of meters en route. As the first male to find a calling female is most
      apt to be her mate, this can be termed "a race to find the female" and it is
      assumed to be under strong selective pressure for efficiency and rapidity.
      Locating a distant, odor-linked resource involves two strategies. The first is to
      contact the outer envelope of the odor plume. When wind direction is relatively
      invariant, the plume stretches and then crosswind flights may be favored,
      although when wind direction shifts over 60 degrees , upwind and downwind paths
      may be optimal. Alternatively, the path may be random with respect to the
      direction of wind flow, with periodic changes in direction, as in either Levy or
      Random Walks. After first detecting the pheromone, a second strategy follows:
      moths navigate along the plume by heading upwind when the pheromone is detected,
      with crosswind casting to re-establish contact if the plume is lost. This
      orientation path is not straightforward in nature, however, because atmospheric
      turbulence fragments the plume, thereby creating large odor gaps. Furthermore, a
      shifting wind direction can lead the responder out of the plume. One way to
      explore which strategies are optimal for enabling initial contact with the plume
      and subsequent navigation is through modeling of plumes' dispersal and of
      insects' flight strategies. Our simulations using the flight characteristics of
      the male gypsy moth (Lymantria dispar) suggest that search strategies similar to
      Levy Walks are most apt to result in a high probability of contact with plumes.
      Although a searching trajectory aimed predominately crosswind performed almost as
      well as those with a random orientation when wind direction was relatively
      stable, downwind biased trajectories were least successful. A random orientation
      with respect to immediate wind flow, as used in our simulations of Levy and
      Random Walks, seems optimal both for initial discovery of the plume and
      likelihood of locating an odor source. In the two available direct field
      observations, moths adopted a random orientation with respect to concurrent wind
      direction. 

PMID- 25980570
TI  - Development and psychometric properties of the Pulmonary-specific Quality-of-Life
      Scale in lung transplant patients.
AB  - BACKGROUND: The Pulmonary-specific Quality-of-Life Scale (PQLS) was developed to
      measure quality of life (QoL) among patients awaiting lung transplant. The
      objective of this study was to determine the psychometric properties of the PQLS,
      identify empirically derived sub-scales, and examine ability to detect changes in
      pulmonary-specific QoL scores after lung transplantation. METHODS: Data were
      derived from the INSPIRE trial, a dual-site randomized controlled trial of coping
      skills training in 389 lung transplant candidates (obstructive [48.3%],
      restrictive [24.2%], cystic fibrosis [13.6%], and other [13.9%]). Cronbach alpha
      was calculated to assess the internal reliability of the PQLS (n = 388). Test
      retest reliability was assessed with correlation coefficients between baseline
      and 12-week post-baseline scores for the usual care control condition (n = 140).
      Convergent validity was assessed with correlation coefficients between the PQLS
      and established measures of QoL and emotional distress, 6-minute walk test
      distance, forced expiratory volume in 1 second, and use of supplemental oxygen at
      rest (n = 388). Change from baseline to 6 months post-transplantation was
      assessed with repeated measures analysis of variance (n = 133). RESULTS: The PQLS
      was internally reliable and stable across 12 weeks. The PQLS correlated strongly
      with QoL measures (e.g., Shortness of Breath Questionnaire, r = 0.78, p <
      0.0001), moderately with mood and anxiety (e.g., Beck Depression Inventory-II, r
      = 0.59, p < 0.0001), and modestly with lung disease severity (e.g., 6-minute walk
      test, r = -0.41, p < 0.0001). PQLS scores improved by nearly 2 SDs after
      transplant. CONCLUSIONS: These results demonstrated the reliability, validity,
      and sensitivity to change of the PQLS for measuring pulmonary QoL among patients
      with advanced lung disease and the responsiveness of the PQLS to changes in QoL
      after lung transplantation.

PMID- 25980571
TI  - Macrovascular and microvascular function after implantation of left ventricular
      assist devices in end-stage heart failure: Role of microparticles.
AB  - BACKGROUND: The hemodynamic vascular consequences of implanting left ventricular
      assist devices (LVADs) have not been studied in detail. We investigated the
      effect of LVAD implantation compared with heart transplant (HTx) on microvascular
      and macrovascular function in patients with end-stage heart failure and evaluated
      whether microparticles may play a role in LVAD-related endothelial dysfunction.
      METHODS: Vascular function was assessed in patients with end-stage heart failure
      awaiting HTx, patients who had undergone implantation of a continuous-flow
      centrifugal LVAD, and patients who had already received a HTx. Macrovascular
      function was measured by flow-mediated vasodilation (FMD) using high-resolution
      ultrasound of the brachial artery. Microvascular function was assessed in the
      forearm during reactive hyperemia using laser Doppler perfusion imaging and
      pulsed wave Doppler. Age-matched patients without heart failure and without
      coronary artery disease (CAD) (healthy control subjects) and patients with stable
      CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte
      (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-),
      CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free
      hemoglobin by enzyme-linked immunosorbent assay. RESULTS: FMD and microvascular
      function were significantly impaired in patients with end-stage heart failure
      compared with healthy control subjects and patients with stable CAD. LVAD
      implantation led to recovery of microvascular function, but not FMD. In parallel,
      increased free hemoglobin was observed along with red and white cell
      microparticles and endothelial and platelet microparticles. This finding
      indicates destruction of blood cells with release of hemoglobin and activation of
      endothelial cells. HTx and LVAD implantation led to similar improvements in
      microvascular function. FMD increased and microparticle levels decreased in
      patients with HTx, whereas shear stress during reactive hyperemia was similar in
      patients with LVADs and patients with HTx. CONCLUSIONS: Our data suggest that
      LVAD support leads to significant improvements in microvascular perfusion and
      hemodynamics. However, destruction of blood cells may contribute to residual
      endothelial dysfunction potentially by increasing nitric oxide scavenging
      capacity.

PMID- 25980572
TI  - Maintenance steroid use at 30 days post-transplant and outcomes of pediatric
      heart transplantation: A propensity matched analysis of the Pediatric Heart
      Transplant Study database.
AB  - BACKGROUND: Maintenance steroid (MS) use in pediatric heart transplantation is
      variable. The purpose of this study was to evaluate the impact of MS use on graft
      outcomes. METHODS: All patients <18 years old in the Pediatric Heart Transplant
      Study database at the time of first heart transplant between 1993 and 2011 who
      survived >=30 days post-transplant and were from centers with a protocolized
      approach to MS use were included (N = 2,178). Patients were grouped by MS use at
      30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was
      used to generate matched groups of MS+ and MS- patients based on pre-transplant
      and peri-transplant factors. Kaplan-Meier survival analysis was used to compare
      freedom from graft loss, graft loss secondary to rejection, rejection, rejection
      with severe hemodynamic compromise (RSHC), malignancy, and infection between
      groups. RESULTS: Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There
      were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier
      estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to
      rejection (p = 0.09). At 1 year post-transplant, there was no difference in
      freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower
      freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02,
      respectively). CONCLUSIONS: MS use at 30 days post-transplant was not associated
      with enhanced graft survival after pediatric heart transplant. MS- patients had a
      higher incidence of RSHC and infection. These risks should be taken into
      consideration when determining MS use for pediatric recipients of heart
      transplants.

PMID- 25980573
TI  - Application of avidin-biotin technology to improve cell adhesion on nanofibrous
      matrices.
AB  - BACKGROUND: Electrospinning is an easy and effective technique to produce
      submicron fibers possessing a range of attractive characteristics such as
      interconnected porous structures similar to natural ECM and good resilience to
      movement. Rapid and efficient cell attachment to nanofibrous matrices is a
      necessary prerequisite in tissue engineering. Thus, the aim of this study is to
      evaluate poly(epsilon-caprolactone-co-lactide)/Pluronic (PLCL/Pluronic)
      nanofibrous matrices with avidin-biotin technology for improving cell adhesion
      for the first time. RESULTS: PLCL/Pluronic nanofibers had relatively homogeneous
      fibers and interconnected porous structures. Pluronic significantly modified the
      hydrophilicity of nanofibrous matrices and PLCL/Pluronic nanofibrous matrices had
      better performance on maintaining cell proliferation. Avidin-biotin technology
      had no negative effect on the hydrophilic property, mechanical property and cell
      proliferation. Meanwhile, the attachment and spreading of adipose-derived stem
      cells (ADSCs) onto PLCL/Pluronic nanofibrous matrices with avidin-biotin
      technology was promoted obviously. CONCLUSIONS: PLCL/Pluronic nanofibrous
      matrices inheriting the excellent characteristics of both PLCL and Pluronic have
      the better cell adhesion ability through avidin-biotin technology, implying a
      promising application in skin care, tissue regeneration and other related area.

PMID- 25980574
TI  - Natural products-friends or foes?
AB  - A trend in the general population has been observed in recent years regarding the
      orientation toward preventive measures in health; in this context the increased
      interest from the users and researchers concerning the active effect of food
      supplements on the health state and on longevity, is noticeable. All over the
      world, the consumption of natural foods and of vegetal supplements has increased
      spectacularly over the last 5-10 years. The decreased prevalence of cardio
      vascular diseases associated with Mediterranean diet, as well as the French
      paradox convinced researchers to scientifically document the beneficial outcomes
      pointed out by traditional use of plants, and to try to develop supplements that
      would have the same positive effects as these noticed for diet components. The
      intense research dedicated to this topic revealed the fact that food supplements
      are linked to some problematic aspects, such as toxicological side effects when
      associated with classical synthetic drugs. The food supplement-drug interactions
      are submitted to complex issues regarding pharmacokinetic interactions leading to
      changes in absorption, distribution, metabolism and excretion processes with
      direct impact on effect and toxicological potential. The present review based on
      recent literature aims at discussing the food-drug interactions with direct
      impact on efficacy and toxicity of drugs. 

PMID- 25980575
TI  - Activation of liver X receptors inhibits cadmium-induced apoptosis of human renal
      proximal tubular cells.
AB  - Liver X receptors (LXRs) including LXRalpha and LXRbeta are members of the
      nuclear receptor superfamily of ligand-activated transcription factors, which are
      expressed in high metabolic organs such as the liver, kidney, and adipose tissue.
      LXRs have been shown to act as antioxidants and anti-inflammatory in several
      organs. The present study investigated the effects of LXR activation on cadmium
      induced cell death in renal proximal tubular cells. Treating human renal proximal
      tubular cells, HK-2 cells, with 20MUM CdCl2 for 24h led to cell death via
      apoptosis but not necrosis. Interestingly, pretreating HK-2 cells with T0901317,
      a LXR agonist, significantly inhibited the apoptotic cell death induced by CdCl2.
      The protective effect of T0901317 was eliminated by incubation with fenofibrate,
      a LXR antagonist, indicating that the effect of T0901317 on cadmium-induced
      apoptotic cell death was mediated by LXR activation. In addition, the effect of
      CdCl2 was attenuated by a reactive oxygen species (ROS) scavenger, N-acetyl-l
      cysteine (NAC). An increase in ROS induced by CdCl2 was mediated by inhibition of
      catalase but not superoxide dismutase (SOD) which was attenuated by T0901317.
      Western blot analysis revealed that CdCl2 stimulated expression of c-jun N
      terminal kinase (JNK) phosphorylation and the stimulation were inhibited by NAC,
      indicating the induction of JNK phosphorylation was stimulated following ROS
      production. Moreover, the increases of ROS and JNK phosphorylation induced by
      CdCl2 were attenuated by LXR activation. This study provides the first evidence
      to show LXR activation reduces cadmium-induced apoptotic cell death of human
      renal proximal tubular cells by inhibition of ROS production and JNK activation.

PMID- 25980577
TI  - Actionable mutations in plasma cell-free DNA in patients with advanced cancers
      referred for experimental targeted therapies.
AB  - Cell-free (cf) DNA in the plasma of cancer patients offers an easily obtainable
      source of biologic material for mutation analysis. Plasma samples from 157
      patients with advanced cancers who progressed on systemic therapy were tested for
      21 mutations in BRAF, EGFR, KRAS, and PIK3CA using the BEAMing method and results
      were compared to mutation analysis of archival tumor tissue from a CLIA-certified
      laboratory obtained as standard of care from diagnostic or therapeutic
      procedures. Results were concordant for archival tissue and plasma cfDNA in 91%
      cases for BRAF mutations (kappa = 0.75, 95% confidence interval [CI] 0.63 -
      0.88), in 99% cases for EGFR mutations (kappa = 0.90, 95% CI 0.71- 1.00), in 83%
      cases for KRAS mutations (kappa = 0.67, 95% CI 0.54 - 0.80) and in 91% cases for
      PIK3CA mutations (kappa = 0.65, 95% CI 0.46 - 0.85). Patients (n = 41) with > 1%
      of KRAS mutant cfDNA had a shorter median survival compared to 20 patients with
      </= 1% of KRAS mutant DNA (4.8 vs. 7.3 months, p=0.008). Similarly, 67 patients
      with >1% of mutant cfDNA (BRAF, EGFR, KRAS, or PIK3CA) had a shorter median
      survival compared to 33 patients with </= 1% of mutant cfDNA (5.5 vs. 9.8 months,
      p = 0.001), which was confirmed in multivariable analysis. [Corrected]

PMID- 25980576
TI  - 2015 heart rhythm society expert consensus statement on the diagnosis and
      treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and
      vasovagal syncope.

PMID- 25980578
TI  - Targeting the inhibitory receptor CTLA-4 on T cells increased abscopal effects in
      murine mesothelioma model.
AB  - We previously demonstrated that blockade of immune suppressive CTLA-4 resulted in
      tumor growth delay when combined with chemotherapy in murine mesothelioma. Tumor
      infiltrating T cells (TIT) after local radiotherapy (LRT) play critical roles in
      abscopal effect against cancer. We attempt to improve the local and abscopal
      effect by modulating T cell immunity with systemic blockade of CTLA-4 signal.The
      growth of primary tumors was significantly inhibited by LRT while CTLA-4 antibody
      enhanced the antitumor effect. Growth delay of the second tumors was achieved
      when the primary tumor was radiated. LRT resulted in more T cell infiltration
      into both tumors, including Treg and cytotoxic T cells. Interestingly, the
      proportion of Treg over effector T cells in both tumors was reversed after CTLA-4
      blockade, while CD8 T cells were further activated. The expression of the immune
      related genes was upregulated and cytokine production was significantly
      increased. LRT resulted in an increase of TIT, while CTLA-4 blockade led to
      significant reduction of Tregs and increase of cytotoxic T cells in both tumors.
      The abscopal effect is enhanced by targeting the immune checkpoints through
      modulation of T cell immune response in murine mesothelioma. 

PMID- 25980579
TI  - Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung
      cancer.
AB  - Here we found loss of c-Cbl, an E3 ligase, expression in non-small cell lung
      cancer (NSCLC) compared with its adjacent normal tissue in patient specimens.
      HDAC inhibition by WJ or knockdown of HDAC 1, HDAC2, HDAC3 or HDAC6 all induced c
      Cbl. Ectopic expression of c-Cbl induced decreased EGFR, inhibited growth in
      NSCLC cells. Knockdown of EGFR inhibited NSCLC growth. Mutation of EGFR at Y1045
      decreased WJ-induced growth inhibition as well as in vivo anti-cancer effect and
      EGFR degradation mediated by WJ. Time-lapse confocal analysis showed co
      localization of c-Cbl and EGFR after WJ treatment. Furthermore, WJ inhibited lung
      tumor growth through c-Cbl induction in orthotopic and tail vein injected models.
      C-Cbl up-regulation induced by HDACi is a potential strategy for NSCLC treatment.

PMID- 25980580
TI  - Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype.
AB  - Metabolic flexibility might be particularly constrained in tumors bearing
      mutations in isocitrate dehydrogenase 1 (IDH1) leading to the production of the
      oncometabolite 2-hydroxygluratate (2HG). To test the hypothesis that IDH1
      mutations could generate metabolic vulnerabilities for therapeutic intervention,
      we utilized an MCF10A cell line engineered with an arginine-to-histidine
      conversion at position 132 (R132H) in the catalytic site of IDH1, which equips
      the enzyme with a neomorphic alpha-ketoglutarate to 2HG reducing activity in an
      otherwise isogenic background. IDH1 R132H/+ and isogenic IDH1 +/+ parental cells
      were screened for their ability to generate energy-rich NADH when cultured in a
      standardized high-throughput Phenotype MicroArrayplatform comprising >300
      nutrients. A radical remodeling of the metabotype occurred in cells carrying the
      R132H mutation since they presented a markedly altered ability to utilize
      numerous carbon catabolic fuels. A mitochondria toxicity-screening modality
      confirmed a severe inability of IDH1-mutated cells to use various carbon
      substrates that are fed into the electron transport chain at different points.
      The mitochondrial biguanide poisons, metformin and phenformin, further impaired
      the intrinsic weakness of IDH1-mutant cells to use certain carbon-energy sources.
      Additionally, metabolic reprogramming of IDH1-mutant cells increased their
      sensitivity to metformin in assays of cell proliferation, clonogenic potential,
      and mammosphere formation. Targeted metabolomics studies revealed that the
      ability of metformin to interfere with the anaplerotic entry of glutamine into
      the tricarboxylic acid cycle could explain the hypersensitivity of IDH1-mutant
      cells to biguanides. Moreover, synergistic interactions occurred when metformin
      treatment was combined with the selective R132H-IDH1 inhibitor AGI-5198.
      Together, these results suggest that therapy involving the simultaneous targeting
      of metabolic vulnerabilities with metformin, and 2HG overproduction with mutant
      selective inhibitors (AGI-5198-related AG-120 [Agios]), might represent a
      worthwhile avenue of exploration in the treatment of IDH1-mutated tumors. 

PMID- 25980582
TI  - The impact of tailored text messages on health beliefs and medication adherence
      in adults with diabetes: A randomized pilot study.
AB  - BACKGROUND: Inadequate medication adherence reduces optimal health outcomes and
      can lead to increased costs, particularly in patients with diabetes. Efforts to
      improve adherence have resulted in limited effects; approaches leveraging mobile
      technology have emerged, but their focus has mainly been limited to simple
      reminder messages. OBJECTIVE: The purpose of this pilot study was to test the
      effectiveness of tailored text messages focusing on improving medication
      adherence and health beliefs in adults with diabetes. METHODS: Adults aged 21-64,
      with uncontrolled diabetes, and taking at least one anti-diabetic medication were
      recruited and randomized into 2 study arms: daily tailored text messaging for 90
      days or standard care. Comparing baseline and endpoint survey responses, changes
      in theory-driven health beliefs and attitudes were assessed. The impact on
      medication adherence was evaluated using pharmacy claims by calculating the
      percent of days covered (PDC). RESULTS: A total of 75 subjects were consented,
      and 48 were randomized. Mean PDC at baseline were comparable between cohorts
      (84.4% and 87.1%, respectively). Declines in adherence were observed in both
      groups over time but no significant differences were observed between groups or
      from baseline to the end of the active study period. Unadjusted tests suggested
      that perceived benefits and competence might have improved in the intervention
      arm. CONCLUSIONS: Tailoring mobile phone text messages is a novel way to address
      medication nonadherence and health beliefs; further investigation to this
      combined technique is needed to better understand its impact on behavior change
      in adults with diabetes.

PMID- 25980581
TI  - ING5 suppresses proliferation, apoptosis, migration and invasion, and induces
      autophagy and differentiation of gastric cancer cells: a good marker for
      carcinogenesis and subsequent progression.
AB  - Here, we found that ING5 overexpression increased autophagy, differentiation, and
      decreased proliferation, apoptosis, migration, invasion and lamellipodia
      formation in gastric cancer cells, while ING5 knockdown had the opposite effects.
      In SGC-7901 transfectants, ING5 overexpression caused G1 arrest, which was
      positively associated with 14-3-3 overexpression, Cdk4 and c-jun hypoexpression.
      The induction of Bax hypoexpression, Bcl-2, survivin, 14-3-3, PI3K, p-Akt and
      p70S6K overexpression by ING5 decreased apoptosis in SGC-7901 cells. The
      hypoexpression of MMP-9, MAP1B and flotillin 2 contributed to the inhibitory
      effects of ING5 on migration and invasion of SGC-7901 cells. ING5 overexpression
      might activate both beta-catenin and NF-kappaB pathways in SGC-7901 cells, and
      promote the expression of down-stream genes (c-myc, VEGF, Cyclin D1, survivin,
      and interleukins). Compared with the control, ING5 transfectants displayed drug
      resistance to triciribine, paclitaxel, cisplatin, SAHA, MG132 and parthenolide,
      which was positively related to their apoptotic induction and the overexpression
      of chemoresistance-related genes (MDR1, GRP78, GRP94, IRE, CD147, FBXW7, TOP1,
      TOP2, MLH1, MRP1, BRCP1 and GST-pi). ING5 expression was higher in gastric cancer
      than matched mucosa. It was inversely associated with tumor size,
      dedifferentiation, lymph node metastasis and clinicopathological staging of
      cancer. ING5 overexpression suppressed growth, blood supply and lung metastasis
      of SGC-7901 cells by inhibiting proliferation, enhancing autophagy and apoptosis
      in xenograft models. It was suggested that ING5 expression might be employed as a
      good marker for gastric carcinogenesis and subsequent progression by inhibiting
      proliferation, growth, migration, invasion and metastasis. ING5 might induce
      apoptotic and chemotherapeutic resistances of gastric cancer cells by activating
      beta-catenin, NF-kappaB and Akt pathways. 

PMID- 25980583
TI  - Prior authorization policies in Medicaid programs: The importance of study design
      and analysis on findings and outcomes from research.
AB  - U.S. State Medicaid programs for the medically indigent strive to deliver quality
      health care services with limited budgets. An often used cost management strategy
      is prior authorization of services or prescription medications. The goal of this
      strategy is to shape the pharmaceutical market share in the most efficient manner
      for the particular state Medicaid program, much like commercial managed care
      organizations. These policies are often scrutinized due to the population
      Medicaid serves, which in the past was largely composed of individuals with
      vulnerable health status. Unintended consequences can occur if these policies are
      not carried out in an appropriate manner or if they greatly restrict services.
      The data used for policy implementation research is prone to certain problems
      such as skewness and multimodality. Previous guidelines have been published
      regarding the best practices when analyzing these data. These guidelines were
      used to review the current body of literature regarding prior authorization in
      Medicaid. Further discussed are additional characteristics such as therapeutic
      areas researched and the outcomes identified. Finally, the importance of
      considering state-specific characteristics when reviewing individual policies and
      the usefulness of these results for other programs are also considered. 

PMID- 25980584
TI  - Chimaphilin inhibits proliferation and induces apoptosis in multidrug resistant
      osteosarcoma cell lines through insulin-like growth factor-I receptor (IGF-IR)
      signaling.
AB  - Chimaphilin, an active compound separated from pyrola, possesses the highly
      efficient antitumor activities. Insulin-like growth factor-I receptor (IGF-IR)
      plays an important role in tumor cell survival. To look for effective strategies
      for interrupting IGF-IR signaling pathway, we found that chimaphilin can inhibit
      the receptor tyrosine kinase activity of IGF-IR. Chimaphilin inhibited the growth
      of both drug-sensitive and drug-resistant osteosarcoma cell lines in a time and
      dose-dependent manner; however, it showed relatively little toxicity in normal
      osteoblast cell lines. Chimaphilin can increase the sensitivity of doxorubicin in
      doxorubicin-resistant osteosarcoma cell lines. Additionally, small interfering
      RNA downregulation of IGF-IR expression in drug-resistant cell lines also caused
      resensitization to doxorubicin. Above all, we conclude that chimaphilin
      represents a valuable natural source and may potentially be applicable for
      reversing the drug-resistant phenotype in osteosarcoma therapy. 

PMID- 25980585
TI  - The anti-inflammatory effect of 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl
      phenol by targeting Lyn kinase in human neutrophils.
AB  - The undesirable respiratory burst in neutrophils can lead to inflammation and
      tissue damage. This study investigates the effect and the underlying mechanism of
      2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol (honokiol), a lignan
      extracted from the stem bark of Magnolia officinalis Rehd. et Wils
      (Magnoliaceae), on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced
      respiratory burst in human neutrophils. Signaling pathways regulated by honokiol
      which modulate fMLP-induced respiratory burst and cathepsin G release were
      evaluated by phosphorylation of Src family kinase induced by fMLP, Src family
      kinases activities and by immunoblotting analysis of the downstream targets of
      Src kinase. Briefly, honokiol inhibited fMLP-induced superoxide anion production
      (IC50 = 9.80 +/- 0.21 MUM, n = 4), cathepsin G release (IC50 = 14.23 +/- 1.43
      MUM, n = 4) and migration (IC50 = 5.69 +/- 1.51 MUM, n = 4) in a concentration
      dependent manner. Further, honokiol specifically suppresses fMLP-induced Lyn (a
      member of the Src kinase family) phosphorylation, by inhibiting Lyn kinase
      activity. Consequently, honokiol attenuated the downstream targets of Lyn kinase,
      such as Tec translocation from the cytosol to the inner leaflet of the plasma
      membrane, phosphorylation of AKT, P38, PLCgamma2, protein kinase C and membrane
      localization of p47(phox). On the other hand, fMLP-induced phosphorylation of
      Hck, Fgr kinase activity (other members of Src kinase), downstream
      phosphorylation of Vav1 and extracellular signal-regulated kinase remained
      unaffected. In addition, honokiol neither inhibited NADPH oxidase activity nor
      increased cyclic AMP levels. Honokiol is not a competitive or allosteric
      antagonist of fMLP. In conclusion, honokiol specifically modulates fMLP-mediated
      neutrophil activation by inhibiting Lyn activation which subsequently interferes
      with the activation of PLCgamma2, AKT, p38, protein kinase C, and p47(phox).

PMID- 25980586
TI  - Synthesis, characterization and analysis of the acrylamide- and glycidamide
      glutathione conjugates.
AB  - Acrylamide (AA) is reported present in high-temperature-processed food and
      classified as a possible human carcinogen. In vivo metabolic activation of AA by
      CYP 2E1 to glycidamide (GA) may play an important role on AA carcinogenicity. AA
      and GA can be detoxified by glutathione-S-transferase to form AA and isomeric GA
      glutathione conjugates (AA-, GA2- and GA3-GSH, respectively), which can be
      further metabolized to mercapturic acids (MAs). Although many studies analyzed
      MAs in urine of rodents and humans, few studies have characterized and analyzed
      the GSH conjugates. The objectives of this study were to synthesize, purify, and
      characterize AA-GSH, GA2-GSH, GA3-GSH, ((13)C3)-AA-GSH, ((13)C3)-GA2-GSH, and
      ((13)C3)-GA3-GSH to develop an isotope-dilution liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method to analyze AA- and GA-GSHs in blood of rats
      treated with AA. After purification and characterization of these conjugates, the
      LC-MS/MS method was developed and validated. This method reveals a limit of
      detection (S/N=3) at 0.017 and a limit of quantitation (S/N=10) at 0.05ng/mL of
      serum for AA-GSH, 0.075 and 0.25ng/mL for GA2-GSH, and 0.15 and 0.5ng/mL for GA3
      GSH. Analyzed with this method, AA-GSH, GA2-GSH and GA3-GSH were 1651.1+/-374.5,
      18.4+/-6.3 and 75.3+/-31.3ng/mL in blood of male rats at 2h after treatment with
      5mg/kgbw of AA by ip injection. These results showed that the LC-MS/MS method was
      successfully developed to analyze AA-GSH, GA2-GSH and GA3-GSH with satisfying
      sensitivity of AA and GA which were conjugated by glutathione in vivo. 

PMID- 25980588
TI  - Permethylated Anigopreissin A inhibits human hepatoma cell proliferation by
      mitochondria-induced apoptosis.
AB  - Anigopreissin A belongs to stilbene di- and oligomeric forms containing a
      benzofuran ring system whose biological activity is unknown. Recently, a
      completely protected Anigopreissin A - Permethylated Anigopreissin A - has been
      synthesized. We use MTT bioassay to assess Permethylated Anigopreissin A
      cytotoxicity in different human cell lines. Furthermore, fluorescence microscopy,
      caspase activity, real-time PCR and Western-blot methods are employed to evaluate
      apoptotic cell death pathway in liver cancer cells. Permethylated Anigopreissin A
      kills different types of human cancer cells but does not affect non-tumorigenic
      cells. The Permethylated Anigopreissin A concentration that causes 50% inhibition
      of liver tumor cells is 0.24MUM. Hepatoma cells treated with Permethylated
      Anigopreissin A arrest their cell cycle in G1 phase. We also demonstrate that
      Permethylated Anigopreissin A-triggered cell death occurs by apoptosis. Decrease
      of the BCL2 expression levels, loss of the mitochondrial membrane potential,
      release of cytochrome c and increase of caspase 9 activity highlight a key role
      for mitochondria in Permethylated Anigopreissin A-induced apoptosis. Our study
      shows that Permethylated Anigopreissin A kills liver cancer cells through
      intrinsic apoptotic pathway. 

PMID- 25980587
TI  - Vinpocetine reduces lipopolysaccharide-induced inflammatory pain and neutrophil
      recruitment in mice by targeting oxidative stress, cytokines and NF-kappaB.
AB  - In response to lipopolysaccharide (LPS), tissue resident macrophages and
      recruited neutrophils produce inflammatory mediators through activation of Toll
      like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappaB) signaling pathway.
      These mediators include inflammatory cytokines and reactive oxygen species that,
      in turn, sensitize nociceptors and lead to inflammatory pain. Vinpocetine is a
      nootropic drug widely used to treat cognitive and neurovascular disorders, and
      more recently its anti-inflammatory properties through inhibition of NF-kappaB
      activation have been described. In the present study, we used the intraplantar
      and intraperitoneal LPS stimulus in mice to investigate the effects of
      vinpocetine pre-treatment (3, 10, or 30mg/kg by gavage) in hyperalgesia,
      leukocyte recruitment, oxidative stress, and pro-inflammatory cytokine production
      (TNF-alpha, IL-1beta, and IL-33). LPS-induced NF-kappaB activation and cytokine
      production were investigated using RAW 264.7 macrophage cell in vitro.
      Vinpocetine (30mg/kg) significantly reduces hyperalgesia to mechanical and
      thermal stimuli, and myeloperoxidase (MPO) activity (a neutrophil marker) in the
      plantar paw skin, and also inhibits neutrophil and mononuclear cell recruitment,
      superoxide anion and nitric oxide production, oxidative stress, and cytokine
      production (TNF-alpha, IL-1beta and IL-33) in the peritoneal cavity. At least in
      part, these effects seem to be mediated by direct effects of vinpocetine on
      macrophages, since it inhibited the production of the same cytokines (TNF-alpha,
      IL-1beta and IL-33) and the NF-kappaB activation in LPS-stimulated RAW 264.7
      macrophages. Our results suggest that vinpocetine represents an important
      therapeutic approach to treat inflammation and pain induced by a gram-negative
      bacterial component by targeting NF-kappaB activation and NF-kappaB-related
      cytokine production in macrophages. 

PMID- 25980589
TI  - A natural piper-amide-like compound NED-135 exhibits a potent inhibitory effect
      on the invasive breast cancer cells.
AB  - Invasiveness and metastasis are the primary factors indicating poor prognosis in
      breast cancer patients. To identify a novel lead compound for the development of
      therapeutics for the treatment of breast cancer through inhibiting invasion, we
      screened the natural piper amide-like compounds library that we previously
      constructed. Among the compounds tested, (E)-3-(3,4-dimethoxyphenyl)-N-(4
      hydroxyphenethyl)acrylamide (NED-135) showed potent inhibitory effects on matrix
      metalloproteinase (MMP)-9 and invasiveness of MCF10A human breast epithelial
      cells treated with an inflammatory lipid, sphingosine-1-phosphate (S1P). The
      invasive phenotypes of MDA-MB-231 and Hs578T triple-negative breast cancer cells
      were significantly inhibited by NED-135. NED-135 efficiently inhibited the S1P
      induced MMP-9 expression at the transcriptional level with a comparable degree to
      FTY720, a known antagonist of S1P. We further showed that NED-135 significantly
      inhibited activation of S1P-induced signaling molecules, Akt, ERKs, and p38 MAPK.
      Computational similarity analysis led us to postulate that NED-135 and FTY720 may
      exert anti-invasive effects on breast cells possibly via different mechanisms.
      Due to its novel structural and functional features, we suggest that NED-135 can
      be used as a novel lead compound against breast cancer in an inflammatory
      microenvironment and highly invasive triple-negative breast cancer. 

PMID- 25980590
TI  - An insight into antagonist binding and induced conformational dynamics of class B
      GPCR corticotropin-releasing factor receptor 1.
AB  - The human corticotropin-releasing factor receptor type 1 (CRF1R) is a class B G
      protein-coupled receptor (GPCR), which mediates the response to stress and has
      been considered as a drug target for depression and anxiety. Based on the CRF1R
      antagonist crystal structure, we study the binding mechanism of two distinct
      antagonists, CP-376395 and MTIP, and the dynamics behaviors of CRF1R induced by
      an antagonist binding. Key residues interacting with both antagonists and
      residues specifically binding to one of them are identified. Both antagonists
      interact with Asn283, Phe203, Met206, Leu280, Tyr316, Leu323, Leu287, Phe284,
      Val279, Leu319, Phe207, Gly210 and Phe362. CP-376395 specifically binds to Glu209
      and Phe160, while MTIP specifically binds to Leu320, Leu213, Ile290, Phe162 and
      Val313. The total binding free energy of MTIP is lower than that of CP-376395;
      this is consistent with the experimental observation that MTIP shows higher
      binding affinity than CP-376395. The conformational dynamic behaviors of
      antagonist bound holo-CRF1R were found to be different from those of apo-CRF1R in
      three aspects: (i) the "ionic lock" between side chains of Arg151 in TM2 and
      Glu209 in TM3 was broken in apo-CRF1R, but was formed in holo-CRF1Rs; (ii) Phe203
      in TM3 and Tyr327 in TM6 were in close proximity to each other in apo-CRF1R,
      while they were far apart resulting from the shift of TM6 in holo-CRF1Rs; and
      (iii) the "rotamer toggle switch", Tyr327/Leu323/Phe284, adopted different
      rotameric conformations in apo-CRF1R and holo-CRF1Rs. We hope that our results
      could be helpful in further development of the drug design of CRF1R. 

PMID- 25980591
TI  - Prediction of treatment response to 131I therapy by diffuse hepatic uptake
      intensity on post-therapy whole-body scan in patients with distant metastases of
      differentiated thyroid cancer.
AB  - OBJECTIVE: A diffuse hepatic uptake (DHU) on radioiodine whole-body scans (WBS)
      after (131)I therapy is caused by (131)I-labeled iodoproteins, particularly
      (131)I-labeled thyroglobulin (Tg). We hypothesized that the DHU intensity after
      (131)I therapy might correlate with subsequent serum Tg reduction, suggesting
      that DHU reflects destruction of functioning thyroid tissue as measured by serum
      Tg. MATERIALS AND METHODS: We retrospectively reviewed the medical records and
      (131)I WBSs of 47 patients treated with (131)I therapy for distant metastasis
      from differentiated thyroid cancer (M:F = 15:32, median age 45 years, range 11-74
      years). All patients received post-ablative (131)I scans (PAWBS) at first (131)I
      ablation after total thyroidectomy and post-therapy (131)I scan (PTWBS) at second
      (131)I therapy. The DHU intensities of the PAWBS and PTWBS were classified into 3
      grades: 1, faint; 2, modest; and 3, intense. Serum thyroid-stimulating hormone
      stimulated Tg (sTg) levels were measured at the time of each therapy and 1 year
      after the second (131)I therapy. RESULTS: One year after the second (131)I
      therapy, 10 patients (21.3%) were in remission and 37 (78.7%) had persistent
      disease. The DHU intensity on PAWBS correlated with the percentage sTg reduction
      at the next follow-up point (sigma = 0.466, p = 0.0016). The patients with
      intense DHU on PTWBS tended to have a higher percentage sTg reduction than the
      other patients, although statistical significances were marginal (Spearman's rank
      correlation: sigma = 0.304, p = 0.054; Kruskal-Wallis test: p = 0.067). In
      univariate analysis, the DHU grades on PAWBS and the initial sTg levels were
      significantly different between patients in remission and those with persistent
      disease (PAWBS: p = 0.022; initial sTg: p = 0.0059). In multivariate logistic
      regression analysis, after adjusting for initial sTg levels, a DHU grade of 3 on
      PAWBS was an independent predictor of remission (PAWBS: p = 0.028; initial sTg
      <100 ng/ml: p = 0.043). CONCLUSIONS: In patients with iodine-avid distant
      metastases, intensity of DHU on (131)I post-therapy scan correlated with
      subsequent percentage serum sTg reduction. Also, intense DHU could be one of the
      predictors of remission in these patients.

PMID- 25980592
TI  - Retraction Note to: Coexpression of HSP47 Gene and Type I and Type III Collagen
      Genes in LPS-Induced Pulmonary Fibrosis in Rats.

PMID- 25980593
TI  - Lymphangioleiomyomatosis: New Treatment Perspectives.
AB  - Lymphangioleiomyomatosis (LAM) is a rare multisystem disease, occurs in women,
      usually premenopausal, caused by the proliferation of neoplastic smooth muscle
      derived cells. Mutations in the tuberous sclerosis complex genes, lead to the
      activation of mammalian target of rapamycin kinase (mTOR), results in
      proliferation of LAM cells, its increasing motility, and survival. Polycystic
      lung destruction, extensive involvement of lymphatic channels, chylothorax,
      chyloperitoneum, and renal angiomyolipomas can develop in LAM patients. The new,
      promising treatment strategies have been recently introduced due to discovery of
      the genetic and molecular mechanisms of LAM. Comprehension of the disease
      pathogenesis has resulted in the implementation of other therapeutic agents such
      as mTOR inhibitors, VEGF-D inhibitors, statins, interferon, chloroquine analogs,
      cyclin-dependent kinase inhibitors, matrix metalloproteinase inhibitors,
      aromatase inhibitors, and their combinations. The mTOR inhibitors appear to be
      the most important, and the efficacy of sirolimus in LAM treatment has been
      proved. The article discussed the new control studies with mTOR inhibitors,
      doxycycline, simvastatin, and combination of them in LAM patients. 

PMID- 25980595
TI  - CASE 7---2015: Perioperative Considerations for a Cardiac Paraganglioma...Not
      Just Another Cardiac Mass.

PMID- 25980596
TI  - Complications and Risk Assessment of 25 Years in Pediatric Pacing.
AB  - BACKGROUND: Children who require cardiac pacemaker implantation have presented a
      small patient sub-population since the breakthrough of this technology in the
      1950s and 1960s. Their small bodies result in a technical challenge for the
      operating surgeon and put the patient at risk for a series of specific
      complications. Our study aims to analyze complications and to identify risk
      factors of endocardial and epicardial pacemaker systems in children. METHODS: All
      pacemaker-related operations in pediatric patients up to the age of 18 years from
      1985 through 2010 were retrospectively evaluated. Demographic data including age,
      height, and weight were recorded. Idiopathic and postoperative dysrhythmias were
      analyzed separately. RESULTS: A total of 149 pacemaker operations were performed
      in 73 patients. Thirty-two patients did not have a previous cardiac operation.
      Indications for revision included box exchange, lead-related problems, pacemaker
      pocket complications, impaired left ventricular function, and pectoral muscle
      stimulation. Increased pacing thresholds occurred in 17.2% of the patients with
      epicardial leads compared with 2.9% in the endocardial group. Aside from
      threshold-related revision, lead problems are more common in the endocardial
      group (30.4% vs 17.2%). Venous thrombosis occurred in 13.7% of the patients (only
      endocardial), preferentially (25%) in the weight group less than 15 kg and in
      idiopathic patients (15.6% vs 10.5% with prior cardiac surgery). CONCLUSIONS:
      Cardiac pacing is particularly challenging in the pediatric patient population
      facing a large number of reoperations during their lifetime. The lack of clear
      superiority of either epicardial or endocardial pacing systems requires an
      individual concept.

PMID- 25980594
TI  - Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib:
      Patterns of disease progression and clinical management of limited progression.
AB  - INTRODUCTION: Vemurafenib induces tumour regression in most patients with
      BRAF(V600E)-mutant melanoma; eventually, most experience progressive disease
      (PD). Long-term follow-up of patients with BRAF(V600E) melanoma treated in the
      phase 1 vemurafenib trial is reported. METHODS: Patients received vemurafenib 240
      1120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily.
      Clinical response was evaluated every 8 weeks by Response Evaluation Criteria In
      Solid Tumors (RECIST). Patients with PD amenable to local therapy (surgery or
      radiotherapy) were allowed to continue vemurafenib after progression. Overall
      survival (OS) from time of treatment initiation and from PD was estimated. Sites
      of PD were recorded. RESULTS: Forty-eight patients (escalation cohort, n = 16;
      extension cohort, n = 32) received therapeutic doses of vemurafenib (? 240 mg
      twice daily). Forty-four patients had PD by the time of this analysis and four
      remained progression free (follow-up time, 1.2-56.1 months). Median OS was 14
      months (range, 1.2-56.1); 3- and 4-year melanoma-specific survival rate in the
      extension cohort was 26% and 19%, respectively. Median OS was 26.0 months (range,
      7.7-56.1) among 20 patients who continued vemurafenib after local therapy. Median
      treatment duration beyond initial PD was 3.8 months (range, 1.1-26.6). In the
      extension cohort, six and five patients were alive after 3 and 4 years,
      respectively, on vemurafenib monotherapy. CONCLUSIONS: Some patients with
      melanoma achieved long-term survival with vemurafenib monotherapy. Continuation
      of vemurafenib after PD might be beneficial in some patients because remaining
      disease might continue to respond to BRAF inhibition.

PMID- 25980597
TI  - Optimal Extent of Lymph Node Dissection for Siewert Type II Esophagogastric
      Junction Adenocarcinoma.
AB  - BACKGROUND: The optimal surgical approach and extent of lymphadenectomy for
      Siewert type II adenocarcinoma of the esophagogastric junction (AEG) is
      controversial. The aim of this study was to identify its optimal extent of
      thoracic and abdominal lymph node dissection, and the appropriate surgical
      approach. METHODS: The clinicopathologic data of 192 patients with Siewert type
      II AEG who were admitted to our center during January 2007 through October 2011
      were retrospectively analyzed. We used the index of estimated benefit from lymph
      node dissection to assess the therapeutic value of lymph node dissection of each
      station. RESULTS: Overall, for the thoracic lymph node dissection, the left
      thoracic route and Ivor-Lewis procedure are better choices than the
      abdominotranshiatal route. While for the abdominal lymph node dissection, the
      abdominotranshiatal achieved a better dissection extent. No significant
      difference was found in metastatic frequency for each station except the 16th
      station. The multivariate analysis found only N stage (p = 0.000) and number of
      resected lymph nodes of 12 or more (p = 0.035) were prognostic factors for
      Siewert type II AEG. Furthermore, we identified two thoracic lymph node stations
      (8M and 8L) and six abdominal lymph node stations (16, 17, 19, 20, G3, G4) that
      have a high therapeutic value for the patients. CONCLUSIONS: We recommend the 8M,
      8L, 16, 17, and G3 should be excised for Siewert type II AEG. Considering the
      lymphadenectomy, the Ivor-Lewis procedure is the optimal choice for patients with
      Siewert type II AEG.

PMID- 25980598
TI  - Race and Hemorrhage in Cerebral Arteriovenous Malformations.

PMID- 25980599
TI  - Prior Experience with Non-Prescribed Buprenorphine: Role in Treatment Entry and
      Retention.
AB  - Buprenorphine availability continues to expand as an effective treatment for
      opioid dependence, but increases in availability have also been accompanied by
      increases in non-prescribed use of the medication. Utilizing data from a
      randomized clinical trial, this mixed-method study examines associations between
      use of non-prescribed buprenorphine and subsequent treatment entry and retention.
      Quantitative analyses (N = 300 African American buprenorphine patients) found
      that patients with prior use of non-prescribed buprenorphine had significantly
      higher odds of remaining in treatment through 6 months than patients who were
      naive to the medication upon treatment entry. Qualitative data, collected from a
      subsample of participants (n = 20), identified three thematic explanations for
      this phenomenon: 1) perceived effectiveness of the medication; 2) cost of
      obtaining prescription buprenorphine compared to purchasing non-prescribed
      medication; and 3) convenience of obtaining the medication via daily-dosing or by
      prescription compared to non-prescribed buprenorphine. These findings suggest a
      dynamic relationship between non-prescribed buprenorphine use and treatment that
      indicates potential directions for future research into positive and negative
      consequences of buprenorphine diversion.

PMID- 25980600
TI  - Estimating the hospitalization burden associated with influenza and respiratory
      syncytial virus in New York City, 2003-2011.
AB  - BACKGROUND: Hospitalization burden associated with influenza and respiratory
      syncytial virus (RSV) is uncertain due to ambiguity in the inference
      methodologies employed for its estimation. OBJECTIVES: Utilization of a new
      method to quantitate the above burden. METHODS: Weekly hospitalization rates for
      several principal diagnoses from 2003 to 2011 in New York City by age group were
      regressed linearly against incidence proxies for the major influenza subtypes and
      RSV adjusting for temporal trends and seasonal baselines. RESULTS: Average annual
      rates of influenza-associated respiratory hospitalizations per 100 000 were
      estimated to be 129 [95% CI (79, 179)] for age <1, 36.3 (21.6, 51.4) for ages 1
      4, 10.6 (7.5, 13.7) for ages 5-17, 25.6 (21.3, 29.8) for ages 18-49, 65.5 (54.0,
      76.9) for ages 50-64, 125 (105, 147) for ages 65-74, and 288 (244, 331) for ages
      >=75. Additionally, influenza had a significant contribution to hospitalization
      rates with a principal diagnosis of septicemia for ages 5-17 [0.76 (0.1, 1.4)],
      18-49 [1.02 (0.3, 1.7)], 50-64 [4.0 (1.7, 6.3)], 65-74 [8.8 (2.2, 15.6)], and
      >=75 [38.7 (25.7, 52.9)]. RSV had a significant contribution to the rates of
      respiratory hospitalizations for age <1 [1900 (1740, 2060)], ages 1-4 [117 (70,
      167)], and >=75 [175 (44, 312)] [including chronic lower respiratory disease, 90
      (43, 140)] as well as pneumonia & influenza hospitalizations for ages 18-49 [6.2
      (1.1, 11.3)] and circulatory hospitalizations for ages >=75 [199 (13, 375)].
      CONCLUSIONS: The high burden of RSV hospitalizations among young children and
      seniors age >=75 suggests the need for additional control measures such as
      vaccination to mitigate the impact of annual RSV epidemics. Our estimates for
      influenza-associated hospitalizations provide further evidence of the burden of
      morbidity associated with influenza, supporting current guidelines regarding
      influenza vaccination and antiviral treatment.

PMID- 25980601
TI  - Muddying the water in brain edema?

PMID- 25980602
TI  - An active second dihydrofolate reductase enzyme is not a feature of rat and
      mouse, but they do have activity in their mitochondria.
AB  - The identification of a second functional dihydrofolate reductase enzyme in
      humans, DHFRL1, led us to consider whether this is also a feature of rodents. We
      demonstrate that dihydrofolate reductase activity is also a feature of the
      mitochondria in both rat and mouse but this is not due to a second enzyme. While
      our phylogenetic analysis revealed that RNA-mediated DHFR duplication events did
      occur across the mammal tree, the duplicates in brown rat and mouse are likely to
      be processed pseudogenes. Humans have evolved the need for two separate enzymes
      while laboratory rats and mice have just one. 

PMID- 25980603
TI  - Regulation of neuronal communication by G protein-coupled receptors.
AB  - Neuronal communication plays an essential role in the propagation of information
      in the brain and requires a precisely orchestrated connectivity between neurons.
      Synaptic transmission is the mechanism through which neurons communicate with
      each other. It is a strictly regulated process which involves membrane
      depolarization, the cellular exocytosis machinery, neurotransmitter release from
      synaptic vesicles into the synaptic cleft, and the interaction between ion
      channels, G protein-coupled receptors (GPCRs), and downstream effector molecules.
      The focus of this review is to explore the role of GPCRs and G protein-signaling
      in neurotransmission, to highlight the function of GPCRs, which are localized in
      both presynaptic and postsynaptic membrane terminals, in regulation of
      intrasynaptic and intersynaptic communication, and to discuss the involvement of
      astrocytic GPCRs in the regulation of neuronal communication. 

PMID- 25980604
TI  - Restraint-based three-dimensional modeling of genomes and genomic domains.
AB  - Chromosomes are large polymer molecules composed of nucleotides. In some species,
      such as humans, this polymer can sum up to meters long and still be properly
      folded within the nuclear space of few microns in size. The exact mechanisms of
      how the meters long DNA is folded into the nucleus, as well as how the regulatory
      machinery can access it, is to a large extend still a mystery. However, and
      thanks to newly developed molecular, genomic and computational approaches based
      on the Chromosome Conformation Capture (3C) technology, we are now obtaining
      insight on how genomes are spatially organized. Here we review a new family of
      computational approaches that aim at using 3C-based data to obtain spatial
      restraints for modeling genomes and genomic domains. 

PMID- 25980605
TI  - Function of human WIPI proteins in autophagosomal rejuvenation of endomembranes?
AB  - Despite the availability of a large pool of experimental approaches and
      hypothetical considerations, the hunt for the enigmatic membrane origin of
      autophagosomes is still on. In mammalian cells proposed scenarios for the
      formation of the autophagosomal membrane include both de novo assembly, and
      rearrangements plus maturation of pre-existing membrane sections from the
      endoplasmic reticulum (ER), plasma membrane, Golgi or mitochondria. Earlier, we
      identified the human WD-repeat protein interacting with phosphoinositides (WIPI)
      family and showed that WIPI proteins function as essential phosphatidylinositol 3
      phosphate (PtdIns3P) effectors at the nascent autophagosome. Interestingly, WIPI
      proteins localize to both pre-existing endomembranes and nascent autophagosomes.
      In this context, and on the basis of historical records on the formation of
      autophagosomes, we discuss with appropriate modesty an alternative perspective on
      the membrane origin of autophagosomes. 

PMID- 25980606
TI  - Cloning of a copper resistance gene cluster from the cyanobacterium Synechocystis
      sp. PCC 6803 by recombineering recovery.
AB  - A copper resistance gene cluster (6 genes, ~8.2 kb) was isolated from the
      cyanobacterium Synechocystis sp. PCC 6803 by recombineering recovery (RR).
      Following integration of a narrow-host-range plasmid vector adjacent to the
      target region in the Synechocystis genome (pSYSX), DNA was isolated from
      transformed cells and the plasmid plus flanking sequence circularized by
      recombineering to precisely clone the gene cluster. Complementation of a copper
      sensitive Escherichia coli mutant demonstrated the functionality of the pcopM
      gene encoding a copper-binding protein. RR provides a novel alternative method
      for cloning large DNA fragments from species that can be transformed by
      homologous recombination.

PMID- 25980608
TI  - Natural flavonoids as antidiabetic agents. The binding of gallic and ellagic
      acids to glycogen phosphorylase b.
AB  - We present a study on the binding of gallic acid and its dimer ellagic acid to
      glycogen phosphorylase (GP). Ellagic acid is a potent inhibitor with Kis of 13.4
      and 7.5 MUM, in contrast to gallic acid which displays Kis of 1.7 and 3.9 mM for
      GPb and GPa, respectively. Both compounds are competitive inhibitors with respect
      to the substrate, glucose-1-phoshate, and non-competitive to the allosteric
      activator, AMP. However, only ellagic acid functions with glucose in a strongly
      synergistic mode. The crystal structures of the GPb-gallic acid and GPb-ellagic
      acid complexes were determined at high resolution, revealing that both ligands
      bind to the inhibitor binding site of the enzyme and highlight the structural
      basis for the significant difference in their inhibitory potency.

PMID- 25980609
TI  - Cross-linking analysis reveals the putative dimer structure of the cyanobacterial
      BLUF photoreceptor PixD.
AB  - PixD is a blue light using flavin (BLUF)-type blue-light photoreceptor
      controlling phototaxis in the cyanobacterium Synechocystis sp. PCC6803. The
      crystal structure of PixD shows a decamer, although in solution an equilibrium is
      maintained between the dimer and decamer. Because the ratio of these two
      conformers is altered by illumination, the equilibrium state determines
      photosensitivity. However, no structural information is available for the PixD
      dimer. Here, we report a predicted structure for the dimer based on docking
      simulation, mutagenesis, and mass spectrometry-based cross-linking analyses. The
      results indicate the importance of the PixD C-terminus for dimer preference and
      photosensitivity. 

PMID- 25980607
TI  - Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria
      and mitophagy.
AB  - UNC-51 like kinase (ULK1) translocates to dysfunctional mitochondria and is
      involved in mitophagy, but the mechanisms responsible for ULK1 activation and
      translocation remain unclear. Here, we found that hypoxia induces phosphorylation
      of ULK1 at Serine-555 by Adenosine 5'-monophosphate (AMP)-activated protein
      kinase (AMPK). Unlike wild-type ULK1, an ULK1 (S555A) mutant cannot translocate
      to mitochondria in response to hypoxia. Inhibition or knockdown of AMPK prevents
      ULK1 translocation and inhibits mitophagy. Finally, the phospho-mimic ULK1
      (S555D) mutant, but not ULK1 (S555A), rescues mitophagy in AMPK-knockdown cells.
      Thus, we conclude that AMPK-dependent phosphorylation of ULK1 is critical for
      translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic
      stress. 

PMID- 25980610
TI  - Lymphotoxin alpha, a novel target of posttranscriptional gene regulation by HuR
      in HepG2 cells.
AB  - The role of the RNA-binding protein human antigen R (HuR) in hepatocarcinogenesis
      is still elusive. By employing short hairpin (sh)RNA-dependent knockdown
      approach, we demonstrate that lymphotoxin alpha (LTalpha) is a target of
      posttranscriptional gene regulation by HuR in hepatocellular carcinoma (HepG2)
      cells. Consequently, the increased mRNA decay upon HuR depletion significantly
      affects lymphotoxin expression at both, the mRNA and protein level. Biotin
      pulldown assay showed that HuR specifically interacts with the 3'-untranslated
      region (3'-UTR) of the LTalpha mRNA. Furthermore, electrophoretic mobility shift
      assay (EMSA) implicates that the RNA-binding critically depends on the RNA
      recognition motif 2 (RRM2) and the hinge region of HuR. 

PMID- 25980611
TI  - A brief review of nucleosome structure.
AB  - The nucleosomal subunit organization of chromatin provides a multitude of
      functions. Nucleosomes elicit an initial ~7-fold linear compaction of genomic
      DNA. They provide a critical mechanism for stable repression of genes and other
      DNA-dependent activities by restricting binding of trans-acting factors to
      cognate DNA sequences. Conversely they are engineered to be nearly meta-stable
      and disassembled (and reassembled) in a facile manner to allow rapid access to
      the underlying DNA during processes such as transcription, replication and DNA
      repair. Nucleosomes protect the genome from DNA damaging agents and provide a
      lattice onto which a myriad of epigenetic signals are deposited. Moreover, vast
      strings of nucleosomes provide a framework for assembly of the chromatin fiber
      and higher-order chromatin structures. Thus, in order to provide a foundation for
      understanding these functions, we present a review of the basic elements of
      nucleosome structure and stability, including the association of linker histones.

PMID- 25980612
TI  - Identification of potential HIV restriction factors by combining evolutionary
      genomic signatures with functional analyses.
AB  - BACKGROUND: Known antiretroviral restriction factors are encoded by genes that
      are under positive selection pressure, induced during HIV-1 infection, up
      regulated by interferons, and/or interact with viral proteins. To identify
      potential novel restriction factors, we performed genome-wide scans for human
      genes sharing molecular and evolutionary signatures of known restriction factors
      and tested the anti-HIV-1 activity of the most promising candidates. RESULTS: Our
      analyses identified 30 human genes that share characteristics of known
      restriction factors. Functional analyses of 27 of these candidates showed that
      over-expression of a strikingly high proportion of them significantly inhibited
      HIV-1 without causing cytotoxic effects. Five factors (APOL1, APOL6, CD164,
      TNFRSF10A, TNFRSF10D) suppressed infectious HIV-1 production in transfected 293T
      cells by >90% and six additional candidates (FCGR3A, CD3E, OAS1, GBP5, SPN,
      IFI16) achieved this when the virus was lacking intact accessory vpr, vpu and nef
      genes. Unexpectedly, over-expression of two factors (IL1A, SP110) significantly
      increased infectious HIV-1 production. Mechanistic studies suggest that the newly
      identified potential restriction factors act at different steps of the viral
      replication cycle, including proviral transcription and production of viral
      proteins. Finally, we confirmed that mRNA expression of most of these candidate
      restriction factors in primary CD4+ T cells is significantly increased by type I
      interferons. CONCLUSIONS: A limited number of human genes share multiple
      characteristics of genes encoding for known restriction factors. Most of them
      display anti-retroviral activity in transient transfection assays and are
      expressed in primary CD4+ T cells.

PMID- 25980614
TI  - Acute kidney injury after orthotopic liver transplantation using living donor
      versus deceased donor grafts: A propensity score-matched analysis.
AB  - Acute kidney injury (AKI) is a common complication after liver transplantation
      (LT). Few studies investigating the incidence and risk factors for AKI after
      living donor liver transplantation (LDLT) have been published. LDLT recipients
      have a lower risk for post-LT AKI than deceased donor liver transplantation
      (DDLT) recipients because of higher quality liver grafts. We retrospectively
      reviewed LDLTs and DDLTs performed at the University of Pittsburgh Medical Center
      between January 2006 and December 2011. AKI was defined as a 50% increase in
      serum creatinine (SCr) from baseline (preoperative) values within 48 hours. One
      hundred LDLT and 424 DDLT recipients were included in the propensity score
      matching logistic model on the basis of age, sex, Model for End-Stage Liver
      Disease score, Child-Pugh score, pretransplant SCr, and preexisting diabetes
      mellitus. Eighty-six pairs were created after 1-to-1 propensity matching. The
      binary outcome of AKI was analyzed using mixed effects logistic regression,
      incorporating the main exposure of interest (LDLT versus DDLT) with the
      aforementioned matching criteria and postreperfusion syndrome, number of units of
      packed red blood cells, and donor age as fixed effects. In the corresponding
      matched data set, the incidence of AKI at 72 hours was 23.3% in the LDLT group,
      significantly lower than the 44.2% in the DDLT group (P = 0.004). Multivariate
      mixed effects logistic regression showed that living donor liver allografts were
      significantly associated with reduced odds of AKI at 72 hours after LT (P =
      0.047; odds ratio, 0.31; 95% confidence interval, 0.096-0.984). The matched
      patients had lower body weights, better preserved liver functions, and more
      stable intraoperative hemodynamic parameters. The donors were also younger for
      the matched patients than for the unmatched patients. In conclusion, receiving a
      graft from a living donor has a protective effect against early post-LT AKI.

PMID- 25980615
TI  - [Prolonged fever Streptococcus equi spp. zooepidemicus (endocarditis aortic
      complicated with mycotic aneurysm infrarenal)].

PMID- 25980616
TI  - [Hookworm infection: An imported disease in Spain].

PMID- 25980613
TI  - Local amino acid sequence patterns dominate the heterogeneous phenotype for the
      collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly
      mutations.
AB  - Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen
      that arises from a single Gly -> X mutation in the collagen chain, varies widely
      in phenotype from perinatal lethal to mild. It is unclear why there is such a
      large variation in the severity of the disease considering the repeating (Gly-X
      Y)n sequence and the uniform rod-like structure of collagen. We systematically
      evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI
      phenotype using integrated bio-statistical approaches, including odds ratio
      analysis and decision tree modeling. We show that different Gly -> X mutations
      have different local sequence patterns that are correlated with lethal and
      nonlethal phenotypes providing a mechanism for understanding the sensitivity of
      local context in defining lethal and non-lethal OI. A number of important trends
      about which factors are related to OI phenotypes are revealed by the bio
      statistical analyses; most striking is the complementary relationship between the
      placement of Pro residues and small residues and their correlation to OI
      phenotype. When Pro is present or small flexible residues are absent nearby a
      mutation site, the OI case tends to be lethal; when Pro is present or small
      flexible residues are absent further away from the mutation site, the OI case
      tends to be nonlethal. The analysis also reveals the dominant role of local
      sequence around mutation sites in the Major Ligand Binding Regions that are
      primarily responsible for collagen binding to its receptors and shows that non
      lethal mutations are highly predicted by local sequence considerations alone
      whereas lethal mutations are not as easily predicted and may be a result of more
      complex interactions. Understanding the sequence determinants of OI mutations
      will enhance genetic counseling and help establish which steps in the collagen
      hierarchy to target for drug therapy.

PMID- 25980617
TI  - Multi-frequency local wavenumber analysis and ply correlation of delamination
      damage.
AB  - Wavenumber domain analysis through use of scanning laser Doppler vibrometry has
      been shown to be effective for non-contact inspection of damage in composites.
      Qualitative and semi-quantitative local wavenumber analysis of realistic
      delamination damage and quantitative analysis of idealized damage scenarios
      (Teflon inserts) have been performed previously in the literature. This paper
      presents a new methodology based on multi-frequency local wavenumber analysis for
      quantitative assessment of multi-ply delamination damage in carbon fiber
      reinforced polymer (CFRP) composite specimens. The methodology is presented and
      applied to a real world damage scenario (impact damage in an aerospace CFRP
      composite). The methodology yields delamination size and also correlates local
      wavenumber results from multiple excitation frequencies to theoretical dispersion
      curves in order to robustly determine the delamination ply depth. Results from
      the wavenumber based technique are validated against a traditional nondestructive
      evaluation method. 

PMID- 25980618
TI  - Incidence of and risk factors for infectious complications in patients with
      cardiac device implantation.
AB  - OBJECTIVES: The use of cardiac implantable electronic device (CIED; pacemakers,
      implantable cardioverter-defibrillators [ICD], cardiac re-synchronized therapy
      [CRT]) implantation, one essential treatment for cardiac arrhythmias, is
      increasing. Infectious complications related to implants are the main reason for
      device removal and patient morbidity. We sought to identify the incidence of
      infectious complications among patients with cardiac device implantation and
      analyze the risk factors for infectious complications. METHODS: A retrospective
      analysis was conducted of 1307 patients (61.5+/-14.2 years-old, 49.6% male) with
      cardiac device implantation from January 1990 to April 2013. We analyzed the
      incidence of infectious complications during the follow-up period. To investigate
      risk factors associated with infectious complications, we conducted a 1:2 matched
      case-control study of patients with infectious complications and controls without
      infectious complications who had the same implantation period and physician.
      RESULTS: Among 1307 patients, 12 had a confirmed device-related infection: 7 with
      a pocket infection and 5 with infective endocarditis. Over a total of 9091.9
      device-years, the incidence of infectious complications was 1.3/1000 device
      years, based on the 12 patients with an infection. ICD (5.1/1000 device-year) had
      a higher incidence of infectious complications than other cardiac devices, and no
      infectious complications were observed among patients with CRT implantation. Mean
      duration from the time of implantation to infection was 2.02+/-1.65 years. In a
      multivariate analysis, the number of prior procedures including wound revision or
      scar revision was an independent risk factor for infectious complications
      (OR=10.88, 95% CI 1.11->999, p=0.040). CONCLUSIONS: Infection was a rare
      complication of cardiac device implantation, but repeated procedures were
      associated with infectious complications.

PMID- 25980619
TI  - Under treatment of pneumonia among children under 5 years of age in a malaria
      endemic area: population-based surveillance study conducted in Manhica district-
      rural, Mozambique.
AB  - BACKGROUND: Integrated Management of Childhood Illness (IMCI) guidelines were
      developed to decrease morbidity and mortality, yet implementation varies across
      settings. Factors associated with poor adherence are not well understood.
      METHODS: We used data from Manhica District Hospital outpatient department and
      five peripheral health centers to examine pneumonia management for children <5
      years old from January 2008 to June 2011. Episodes of IMCI-defined pneumonia
      (cough or difficult breathing plus tachypnea), severe pneumonia (pneumonia plus
      chest wall in-drawing), and/or clinician-diagnosed pneumonia (based on discharge
      diagnosis) were included. RESULTS: Among severe pneumonia episodes, 96.2%
      (2,918/3,032) attended in the outpatient department and 70.0% (291/416) attended
      in health centers were appropriately referred to the emergency department. Age<1
      year, malnutrition and various physical exam findings were associated with
      referral. For non-severe pneumonia episodes, antibiotics were prescribed in 45.7%
      (16,094/35,224). Factors associated with antibiotic prescription included age <1
      year, abnormal auscultatory findings, and clinical diagnosis of pneumonia;
      diagnosis of malaria or gastroenteritis and pallor were negatively associated
      with antibiotic prescription. CONCLUSION: Adherence to recommended management of
      severe pneumonia was high in a hospital outpatient department, but suboptimal in
      health centers. Antibiotics were prescribed in fewer than half of non-severe
      pneumonia episodes, and diagnosis of malaria was the strongest risk factor for
      incorrect management.

PMID- 25980620
TI  - Enhanced paracellular transport of insulin can be achieved via transient
      induction of myosin light chain phosphorylation.
AB  - The intestinal epithelium functions to effectively restrict the causal uptake of
      luminal contents but has been demonstrated to transiently increase paracellular
      permeability properties to provide an additional entry route for dietary
      macromolecules. We have examined a method to emulate this endogenous mechanism as
      a means of enhancing the oral uptake of insulin. Two sets of stable Permeant
      Inhibitor of Phosphatase (PIP) peptides were rationally designed to stimulate
      phosphorylation of intracellular epithelial myosin light chain (MLC) and screened
      using Caco-2 monolayers in vitro. Apical application of PIP peptide 640, designed
      to disrupt protein-protein interactions between protein phosphatase 1 (PP1) and
      its regulator CPI-17, resulted in a reversible and non-toxic transient reduction
      in Caco-2 monolayer trans-epithelial electric resistance (TEER) and opening of
      the paracellular route to 4kDa fluorescent dextran but not 70kDa dextran in
      vitro. Apical application of PIP peptide 250, designed to impede MYPT1-mediated
      regulation of PP1, also decreased TEER in a reversible and non-toxic manner but
      transiently opened the paracellular route to both 4 and 70kDa fluorescent
      dextrans. Direct injection of PIP peptides 640 or 250 with human insulin into the
      lumen of rat jejunum caused a decrease in blood glucose levels that was PIP
      peptide and insulin dose-dependent and correlated with increased pMLC levels.
      Systemic levels of insulin suggested approximately 3-4% of the dose injected into
      the intestinal lumen was absorbed, relative to a subcutaneous injection.
      Measurement of insulin levels in the portal vein showed a time window of
      absorption that was consistent with systemic concentration-time profiles and
      approximately 50% first-pass clearance by the liver. Monitoring the uptake of a
      fluorescent form of insulin suggested its uptake occurred via the paracellular
      route. Together, these studies add validation to the presence of an endogenous
      mechanism used by the intestinal epithelium to dynamically regulate its
      paracellular permeability properties and better define the potential to enhance
      the oral delivery of biopharmaceuticals via a transient regulation of an
      endogenous mechanism controlling the intestinal paracellular barrier. 

PMID- 25980622
TI  - Cellular uptake and in vivo distribution of polyhistidine peptides.
AB  - Cell-penetrating peptides (CPPs) are arginine/lysine-rich sequences, and they are
      effectively internalized into cells. In this process, positive charge is crucial.
      In the present study, we found polyhistidine peptides (PHPs), as the novel CPP,
      which are efficiently internalized into cells in a positive charge-independent
      manner. Interestingly, cellular uptake of the PHPs increased as the chain length
      increased, reaching a maximum uptake at H16 (HHHHHHHHHHHHHHHH-NH2). This H16
      peptide showed up to 14.6-fold higher cell-penetrating capacity against HT1080
      human fibrosarcoma cells relative to a major CPP, the octa-arginine (RRRRRRRR
      NH2) peptide. Cellular uptake of the H16 peptide is mainly due to
      macropinocytosis and most of the H16 peptide localizes in the lysosome and Golgi
      apparatus. However, a cytoplasmic pro-apoptotic domain (KLAKLAKKLAKLAK-NH2)
      conjugated to the H16 peptide showed cytotoxic effects. This indicates that a
      proportion of the H16 peptide escapes from the macropinosome to the cytoplasm. In
      a protein transduction study, green fluorescence protein fused to the H16 peptide
      (GFP-H16) was purified by Ni-NTA chromatography, detected using an anti-His-tag
      antibody and internalized into cells. This serial process reveals that H16
      functions as a His-tag and protein transduction domain. Furthermore, in vivo
      distribution analysis showed that the H16 peptide accumulates immediately in
      tumor tissue and is retained up to 132h following injection into the tumor
      (HT1080 human fibrosarcoma)-bearing mice. This is the first observation of a His
      polymer being internalize into cells efficiently. The findings suggest that PHPs
      are novel CPPs. In particular, the H16 peptide represents a promising drug
      delivery carrier candidate in medical and biotechnological fields. 

PMID- 25980623
TI  - Evidence-based rules from family practice to inform family practice; the learning
      healthcare system case study on urinary tract infections.
AB  - BACKGROUND: Analysis of encounter data relevant to the diagnostic process sourced
      from routine electronic medical record (EMR) databases represents a classic
      example of the concept of a learning healthcare system (LHS). By collecting
      International Classification of Primary Care (ICPC) coded EMR data as part of the
      Transition Project from Dutch and Maltese databases (using the EMR TransHIS),
      data mining algorithms can empirically quantify the relationships of all
      presenting reasons for encounter (RfEs) and recorded diagnostic outcomes. We have
      specifically looked at new episodes of care (EoC) for two urinary system
      infections: simple urinary tract infection (UTI, ICPC code: U71) and
      pyelonephritis (ICPC code: U70). METHODS: Participating family doctors (FDs)
      recorded details of all their patient contacts in an EoC structure using the
      ICPC, including RfEs presented by the patient, and the FDs' diagnostic labels.
      The relationships between RfEs and episode titles were studied using
      probabilistic and data mining methods as part of the TRANSFoRm project. RESULTS:
      The Dutch data indicated that the presence of RfE's "Cystitis/Urinary Tract
      Infection", "Dysuria", "Fear of UTI", "Urinary frequency/urgency", "Haematuria",
      "Urine symptom/complaint, other" are all strong, reliable, predictors for the
      diagnosis "Cystitis/Urinary Tract Infection" . The Maltese data indicated that
      the presence of RfE's "Dysuria", "Urinary frequency/urgency", "Haematuria" are
      all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract
      Infection". The Dutch data indicated that the presence of RfE's "Flank/axilla
      symptom/complaint", "Dysuria", "Fever", "Cystitis/Urinary Tract Infection",
      "Abdominal pain/cramps general" are all strong, reliable, predictors for the
      diagnosis "Pyelonephritis" . The Maltese data set did not present any clinically
      and statistically significant predictors for pyelonephritis. CONCLUSIONS: We
      describe clinically and statistically significant diagnostic associations
      observed between UTIs and pyelonephritis presenting as a new problem in family
      practice, and all associated RfEs, and demonstrate that the significant
      diagnostic cues obtained are consistent with the literature. We conclude that it
      is possible to generate clinically meaningful diagnostic evidence from electronic
      sources of patient data.

PMID- 25980624
TI  - Highly open rhombic dodecahedral PtCu nanoframes.
AB  - Herein, we report a facile strategy that allows one-pot preparation of highly
      open rhombic dodecahedral PtCu alloy nanoframes. Due to the highly open
      structures, the PtCu nanoframes exhibit enhanced catalytic performance in
      methanol electrooxidation, showing a new strategy to create highly active
      catalysts. 

PMID- 25980621
TI  - In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for
      pulmonary drug delivery.
AB  - The development of clinically acceptable albumin-based nanoparticle formulations
      for use in pulmonary drug delivery has been hindered by concerns about the
      toxicity of nanomaterials in the lungs combined with a lack of information on
      albumin nanoparticle clearance kinetics and biodistribution. In this study, the
      in vivo biocompatibility of albumin nanoparticles was investigated following a
      single administration of 2, 20, and 390MUg/mouse, showing no inflammatory
      response (TNF-alpha and IL-6, cellular infiltration and protein concentration)
      compared to vehicle controls at the two lower doses, but elevated mononucleocytes
      and a mild inflammatory effect at the highest dose tested. The biodistribution
      and clearance of (111)In labelled albumin solution and nanoparticles over 48h
      following a single pulmonary administration to mice was investigated by single
      photon emission computed tomography and X-ray computed tomography imaging and
      terminal biodistribution studies. (111)In labelled albumin nanoparticles were
      cleared more slowly from the mouse lung than (111)In albumin solution (64.1+/
      8.5% vs 40.6+/-3.3% at t=48h, respectively), with significantly higher (P<0.001)
      levels of albumin nanoparticle-associated radioactivity located within the lung
      tissue (23.3+/-4.7%) compared to the lung fluid (16.1+/-4.4%). Low amounts of
      (111)In activity were detected in the liver, kidneys, and intestine at time
      points >24h indicating that small amounts of activity were cleared from the lungs
      both by translocation across the lung mucosal barrier, as well as mucociliary
      clearance. This study provides important information on the fate of albumin
      vehicles in the lungs, which may be used to direct future formulation design of
      inhaled nanomedicines. 

PMID- 25980625
TI  - Reprogramming of in situ spinal cord stimulator for covering newly developed
      postthoracotomy pain.
AB  - The objective of this case report is to describe the use of in situ spinal cord
      stimulator (SCS) for postthoracotomy pain syndrome (PTPS). We report a 39-year
      old woman with complex regional pain syndrome type I of the left lower extremity.
      The patient's pain was relieved by a SCS for 1 month before the patient developed
      slipping rib syndrome at her T12 rib from an unrelated trauma. After failed
      conservative treatments and undergoing a thoracotomy procedure, the patient
      developed PTPS. Conservative management with medications and intercostal nerve
      blocks provided short-term relief. An already implanted single Octrode with Eon
      Mini generator (St Jude Neuromodulator, Plano, TX) at the T7 level was
      reprogrammed in attempt to recruit peripheral fibers to target the patient's
      additional areas of chest discomfort. This adjustment improved the pain at the
      left lateral rib area as well as her left leg. The patient was followed for 1
      year, and her quality of life improved since her initial presenting symptoms. The
      use of the SCS in this patient provided significant lasting pain relief for both
      complex regional pain syndrome and PTPS. We believe that the use of SCS should be
      considered as a treatment option for patients with PTPS to avoid side effects
      associated with medications and to provide long-term pain relief.

PMID- 25980626
TI  - Percutaneous gastrostomy tube site pain as a manifestation of liver metastases.
AB  - BACKGROUND: Complications are possible following percutaneous enteral feeding in
      head and neck cancer patients and otolaryngologists should be aware of these as
      well as the possibility of liver metastases from these cancers. CASE REPORT: A 53
      year-old lady was treated by our service for metastatic squamous cell carcinoma
      of unknown primary origin. During radiotherapy treatment, a percutaneous
      endoscopic gastrostomy (PEG) tube was inserted to facilitate patient feeding.
      Severe abdominal pain developed and persisted around site of PEG tube insertion,
      the cause of which was discovered to be newly developed liver metastases from the
      tumor being compressed by the tube. CONCLUSION: Liver metastases should be
      considered in patients developing persistent abdominal pain after PEG insertion.

PMID- 25980627
TI  - Robot-assisted transaxillary thyroidectomy: surgical technique.
AB  - Robot-assisted transaxillary thyroid surgery avoids the need for a neck incision.
      It consists of thyroid lobectomy and isthmectomy for moderately large unilateral
      benign nodules. The surgical imperatives are the same as for conventional
      surgery, but with differences in terms of patient positioning, surgical incision,
      equipment, surgical technique and indications. The purpose of this article is to
      describe the equipment, patient positioning and surgical technique of exclusive
      robot-assisted transaxillary total thyroid lobectomy and isthmectomy.

PMID- 25980628
TI  - The nature of impairments of memory in patients with end-stage renal disease
      (ESRD).
AB  - Possible impairments of memory in end-stage renal disease (ESRD) were
      investigated in two experiments. In Experiment 1, in which stimulus words were
      presented visually, participants were tested on conceptual or perceptual memory
      tasks, with retrieval being either explicit or implicit. Compared with healthy
      controls, ESRD patients were impaired when memory required conceptual but not
      when it required perceptual processing, regardless of whether retrieval was
      explicit or implicit. An impairment of conceptual implicit memory (priming) in
      the ESRD group represented a previously unreported deficit compared to healthy
      aging. There were no significant differences between pre- and immediate post
      dialysis memory performance in ESRD patients on any of the tasks. In Experiment
      2, in which presentation was auditory, patients again performed worse than
      controls on an explicit conceptual memory task. We conclude that the type of
      processing required by the task (conceptual vs. perceptual) is more important
      than the type of retrieval (explicit vs. implicit) in memory failures in ESRD
      patients, perhaps because temporal brain regions are more susceptible to the
      effects of the illness than are posterior regions. 

PMID- 25980629
TI  - Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in
      middle-aged female mice.
AB  - Clinical studies have shown that women during perimenopause and menopause have a
      higher incidence in the diagnoses of psychiatric problems compared with men.
      However, little literature information about the influence of spontaneous
      perimenopause on anxiety- and mood-related behaviors in mice is available. To
      this aim, we compared the behavioral responses of middle-aged and young adult
      female mice both in the diestrus phase in the elevated plus-maze, open field and
      forced swimming tests. In middle-aged mice, the duration of the estrous cycle was
      significantly prolonged compared to young adults, thus indicating that our middle
      aged mice are in the perimenopausal period. In the elevated plus-maze test,
      middle-aged mice explored less the open arms when compared to young adults,
      suggesting an anxiogenic-like phenotype. No significant differences were observed
      in the estrogen plasma levels and emotional behavior in the forced swim and open
      field tests. In conclusion, the spontaneous failure of the estrous cycle
      increased anxiety in middle-aged females. These data suggest that the
      perimenopausal period has a significant influence on anxiety-related behaviors in
      female mice. 

PMID- 25980630
TI  - Single-breath clinical imaging of hyperpolarized (129)Xe in the airspaces,
      barrier, and red blood cells using an interleaved 3D radial 1-point Dixon
      acquisition.
AB  - PURPOSE: We sought to develop and test a clinically feasible 1-point Dixon, three
      dimensional (3D) radial acquisition strategy to create isotropic 3D MR images of
      (129)Xe in the airspaces, barrier, and red blood cells (RBCs) in a single breath.
      The approach was evaluated in healthy volunteers and subjects with idiopathic
      pulmonary fibrosis (IPF). METHODS: A calibration scan determined the echo time at
      which (129)Xe in RBCs and barrier were 90 degrees  out of phase. At this TE,
      interleaved dissolved and gas-phase images were acquired using a 3D radial
      acquisition and were reconstructed separately using the NUFFT algorithm. The
      dissolved-phase image was phase-shifted to cast RBC and barrier signal into the
      real and imaginary channels such that the image-derived RBC:barrier ratio matched
      that from spectroscopy. The RBC and barrier images were further corrected for
      regional field inhomogeneity using a phase map created from the gas-phase (129)Xe
      image. RESULTS: Healthy volunteers exhibited largely uniform (129)Xe-barrier and
      (129)Xe-RBC images. By contrast, (129)Xe-RBC images in IPF subjects exhibited
      significant signal voids. These voids correlated qualitatively with regions of
      fibrosis visible on CT. CONCLUSIONS: This study illustrates the feasibility of
      acquiring single-breath, 3D isotropic images of (129)Xe in the airspaces,
      barrier, and RBCs using a 1-point Dixon 3D radial acquisition.

PMID- 25980631
TI  - Assessment of Right Ventricular Function in Obstructive Sleep Apnea Syndrome and
      Effects of Continuous Positive Airway Pressure Therapy: A Pilot Study.
AB  - BACKGROUND: It is known that obstructive sleep apnea syndrome (OSAS) can affect
      right ventricular (RV) performance even in the absence of systemic hypertension
      and other known cardiac or obstructive pulmonary disease. The purpose of the
      present study was to assess RV function in OSAS using 3-D echocardiography and
      speckle tracking echocardiography (STE) and evaluate changes after continuous
      positive airway pressure (CPAP) treatment. METHODS: Thirty-seven patients with
      OSAS without comorbidities and thirty control subjects were studied using 3-D
      echocardiography and STE. Fifteen patients underwent CPAP therapy and were
      studied before and after treatment. RV 3-D ejection fraction was calculated. Peak
      systolic strain was determined. RV dyssynchrony was defined as SD of the 6 time
      to peak systolic strain values. RESULTS: 3-D RV ejection fraction was lower and
      RV dyssynchrony was greater in patients with moderate-severe OSAS compared with
      control subjects in the presence and absence of pulmonary hypertension. 3-D RV
      ejection fraction and RV dyssynchrony were independently associated with apnea
      hypopnea index. Patients treated with CPAP had significant changes in RV
      parameters. CONCLUSIONS: 3-D RV ejection fraction and RV dyssynchrony were
      abnormal in OSAS patients compared with control subjects and associated with OSAS
      severity. RV 3-D STE abnormalities improved after chronic application of CPAP.

PMID- 25980633
TI  - Determining optimal treatment strategy for diffuse glioma: the emerging role of
      IDH mutations.
AB  - The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes mutate frequently in
      gliomas, and it has become increasingly apparent that IDH mutation status
      accounts for much of the prognostic information previously rendered by
      histological grading. Most glioblastomas (90-95%) are IDH wild-type and most
      lower-grade diffuse gliomas (80%) are IDH-mutant. We examine here how IDH
      mutation status interacts with treatments known to influence survival (surgery,
      chemotherapy and radiotherapy) in patients with gliomas, and the impact of the
      IDH mutations on patients' survival after such treatments. IDH mutations is
      associated with more complete surgical resection of enhancing disease, and with a
      better response to RT. In addition, there is increasing clinical evidence that,
      in certain contexts, IDH mutations predict chemotherapeutic sensitivity.
      Mutations in IDH and other genes are beginning to drive decisions on therapy for
      diffuse gliomas and will likely allow tailoring of treatment by molecular profile
      in the future. 

PMID- 25980632
TI  - Acute High-Intensity Intermittent Aerobic Exercise Reduces Plasma Angiopoietin
      Like 2 in Patients With Coronary Artery Disease.
AB  - BACKGROUND: Circulating levels of angiopoietin-like 2 (ANGPTL2), a
      proinflammatory and proatherogenic protein, are elevated in patients with
      coronary artery disease (CAD). We hypothesized that high-intensity intermittent
      exercise (HIIE), known to be beneficial in patients with CAD, would reduce
      circulating ANGPTL2 levels. METHODS: Plasma levels of ANGPTL2 were measured
      before and 20 minutes, 24 hours, and 72 hours after an acute exercise session in
      a crossover study comparing HIIE to moderate-intensity continuous exercise (MICE)
      in 14 patients with CAD and 20 age-matched and 20 young healthy controls.
      RESULTS: Pre-exercise ANGPTL2 levels were 3-fold higher in patients with CAD than
      in age-matched controls (P < 0.05) and correlated negatively with Vo2max/lean
      body mass (P < 0.0001). In healthy controls, ANGPTL2 levels were low and not
      affected by HIIE or MICE. In patients with CAD, ANGPTL2 levels decreased
      significantly by 41% after 20 minutes of HIIE, a reduction that was maintained
      after 24 and 72 hours (P < 0.05). In contrast, although ANGPTL2 levels decreased
      by 47% after 20 minutes of MICE, they increased by 104% after 24 hours and
      returned to baseline values after 72 hours (P < 0.05). A negative correlation was
      observed between this increase in ANGPTL2 levels and the mean rate-pressure
      product (heart rate * systolic blood pressure; index of myocardial O2
      consumption) measured during MICE, suggesting that subclinical ischemia might
      promote ANGPTL2 expression. CONCLUSIONS: In patients with CAD, circulating
      ANGPTL2 levels are acutely reduced after HIIE and transiently increased after
      MICE. A sustained reduction in circulating ANGPTL2 levels could contribute to the
      chronic beneficial cardiometabolic effects of HIIE in patients with CAD.

PMID- 25980634
TI  - Identification of avian bornavirus in a Himalayan monal (Lophophorus impejanus)
      with neurological disease.
AB  - A one-year-old male Himalayan monal (Lophophorus impejanus) was presented for
      veterinary attention with a history of chronic wasting, weakness and ataxia. The
      bird died, and post-mortem findings included mild non-suppurative encephalitis
      and degenerative encephalopathy, lymphoplasmacytic myenteric ganglioneuritis
      (particularly of the proventriculus), and Wallerian degeneration of the sciatic
      nerves. Avian bornavirus (ABV) was identified in the brain by
      immunohistochemistry and reverse-transcriptase polymerase chain reaction.
      Sequencing of the reverse-transcriptase polymerase chain reaction product
      indicated the presence of ABV genotype 4, which is generally associated with
      disease in psittacine birds. Subsequent to the death of the pheasant, ABV
      genotype 4 was identified at autopsy from a juvenile white-bellied caique
      (Pionites leucogaster) in the same collection. We hypothesize that the pheasant
      became infected through contact with psittacine birds with which it shared an
      aviary. We believe this to be the first reported case of natural ABV infection in
      a bird in the Order Galliformes. 

PMID- 25980635
TI  - Synthesis of piezoelectric and bioactive NaNbO3 from metallic niobium and niobium
      oxide.
AB  - NaNbO3 was synthesized by two different routes, one using metallic niobium
      powder, and another using niobium oxide (Nb2 O5 ) powder. In both routes an
      aqueous sodium hydroxide solution was used to hydrothermally treating the
      powders. In the first approach, the solution concentrations were 3M, 1M, and
      0.5M. The second route used solution concentrations of 10M and 12.5M. After the
      hydrothermal treatments, the powders were heat treated in order to synthesize
      NaNbO3 . The products were characterized by scanning electron microscopy (SEM)
      with energy dispersive spectrometry (EDS), and X-ray diffraction (XRD) with
      Rietveld refinement. The phases were identified by means of X-ray diffraction
      (XRD) with Rietveld refinement. It was observed that the molar concentrations of
      the solutions had opposing effects for each route. An antiferroelectric phase was
      found in both routes. In the niobium metallic route, a ferroelectric phase was
      also synthesized. This study proves that piezoelectric NaNbO3 can be obtained
      after alkali treatment of both Nb and Nb2 O5. (c) 2015 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 104B: 979-985, 2016.

PMID- 25980636
TI  - [Technical criteria of central venous catheters: Anaesthesiologist/intensivist
      and pharmacist opinions].
AB  - INTRODUCTION: The lack of technical information from suppliers and from the
      literature, a wide variety of features and the absence of medical device
      reference document explain the difficulty for medical and pharmaceutical staffs
      to choose a central venous catheter (CVC). The aim of this study was to establish
      the specifications to choose a CVC according to the clinician needs. METHODS: An
      analysis of suppliers' technical documentation and a literature review was
      performed to identify criteria and to collect them in a questionnaire to conduct
      semi-structured interviews between 1 pharmacist and 5
      anaesthesiologists/intensivists. With these interviews, the technical criteria
      were classified according to their importance in 3 levels. RESULTS: Thirteen
      technical criteria were identified after reading the technical documents and the
      literature. Among them, 8 were classified as "essential criteria" (level I) by
      the physicians: J-shaped guide, one clamp on each way, identified lumen,
      radiopacity, graduation every centimeter by 5 to 20 cm from the distal extremity,
      a length of 15 to 25 cm, a single-lumen catheter with a 14 to 16G way and a three
      lumen catheter with 14 to 18G way. Finally, three criteria were classified as
      "intermediate criteria" (level II) and two as "optional criteria" (level III).
      CONCLUSIONS: This collaborative approach allowed to reference new medical devices
      according to the clinicians needs. These CVC are a mean to respect guidelines for
      physicians and nurses and to secure the patient's care.

PMID- 25980638
TI  - Corrigendum.

PMID- 25980637
TI  - Forced degradation studies, and effect of surfactants and titanium dioxide on the
      photostability of paliperidone by HPLC.
AB  - Forced degradation study of paliperidone under hydrolytic, oxidative, thermal and
      photolytic stress conditions was conducted using HPLC. The drug was found to be
      labile under hydrolytic, oxidative and photolytic stress conditions; whereas, it
      was stable under dry heat stress conditions. Effect of anionic, cationic and non
      ionic surfactants applied to the concentration exceeding critical micellar
      concentration on the photostability of paliperidone was also studied by exposing
      the samples to sunlight for 72h. Major degradation of the drug was found in
      presence of cationic and non-ionic surfactants. Effect of titanium dioxide on the
      photo-degradation of paliperidone in solution state was also studied and it was
      found that 53% of the drug was degraded after 72h of exposure to sunlight. A
      common degradation peak was observed in oxidative and TiO2 photocatalysed
      samples. This peak may be due to the generation of N-oxide of paliperidone. The
      same degradation peak was also observed in all other photostability samples.
      Chromatographic separation of drug and its degradation products was achieved on
      an Alltima C8 (250mm*4.6mm, 5MUm) analytical column, using a mobile phase
      consisting of acetonitrile-ammonium acetate buffer with 0.2% triethylamine (pH
      3.5; 20mM) (60:40, v/v) at a flow rate of 1mL/min. Quantification was performed
      with UV detection at 280nm. The method was validated as per ICH guidelines. 

PMID- 25980639
TI  - Antimicrobial Electrospun Biopolymer Nanofiber Mats Functionalized with Graphene
      Oxide-Silver Nanocomposites.
AB  - Functionalization of electrospun mats with antimicrobial nanomaterials is an
      attractive strategy to develop polymer coating materials to prevent bacterial
      colonization on surfaces. In this study we demonstrated a feasible approach to
      produce antimicrobial electrospun mats through a postfabrication binding of
      graphene-based nanocomposites to the nanofibers' surface. A mixture of
      poly(lactide-co-glycolide) (PLGA) and chitosan was electrospun to yield
      cylindrical and narrow-diameter (356 nm) polymeric fibers. To achieve a robust
      antimicrobial property, the PLGA-chitosan mats were functionalized with graphene
      oxide decorated with silver nanoparticles (GO-Ag) via a chemical reaction between
      the carboxyl groups of graphene and the primary amine functional groups on the
      PLGA-chitosan fibers using 3-(dimethylamino)propyl-N'-ethylcarbodiimide
      hydrochloride and N-hydroxysuccinimide as cross-linking agents. The attachment of
      GO-Ag sheets to the surface of PLGA-chitosan fibers was successfully revealed by
      scanning and transmission electron images. Upon direct contact with bacterial
      cells, the PLGA-chitosan mats functionalized with GO-Ag nanocomposites were able
      to effectively inactivate both Gram-negative (Escherichia coli and Pseudomonas
      aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. Our results
      suggest that covalent binding of GO-Ag nanocomposites to the surface of PLGA
      chitosan mats opens up new opportunities for the production of cost-effective,
      scalable, and biodegradable coating materials with the ability to hinder
      microbial proliferation on solid surfaces. 

PMID- 25980640
TI  - Rethinking guideline toxicity testing.
AB  - The guidelines for risk assessment of plant protection products (PPPs) and other
      non-pharmaceuticals were developed over three decades ago and have generally not
      been updated to incorporate advancements in toxicology and exposure sciences.
      These guidelines recommend using maximum-tolerated-dose (MTD) even when human
      relevance of such high doses is mostly limited due to orders of magnitude margin
      of-exposure. Conducting animal studies at such high doses often requires further
      mode-of-action (MoA) studies elucidating human relevance. In order to improve
      data, ILSI/HESI-ACSA technical committee proposed a tiered approach with emphasis
      on determining systemic dose of parent and/or metabolite(s) in test animals as
      biological effects are reflective of systemic rather than administered dose. Any
      deviation from linearity in systemic dose (saturation of absorption or
      elimination) in animal studies may have profound toxic effect(s) not expected to
      occur in likely human exposure scenarios and should be avoided. Toxicity studies
      should ideally be conducted at kinetically linear doses or slightly above the
      point of departure from linearity or kinetically-derived maximum dose (KMD) as
      the systemic dose nonlinearity is a more sensitive parameter occurring much
      earlier than the MTD endpoints. Therefore, determining systemic dose, especially
      KMD, in study animals is an improvement to hazard assessment of PPPs and other
      non-pharmaceuticals allowing toxicologists to better understand findings in
      animals at systemically linear as well as nonlinear doses to likely human
      exposures which can easily be accomplished using core study animals as outlined
      below. Determining systemic dose in studies will also increase the understanding
      of initial potential MoA of a PPPs and other non-pharmaceuticals and reduce the
      use of animals by avoiding unnecessary additional MoA studies. 

PMID- 25980641
TI  - A practical application of two in silico systems for identification of
      potentially mutagenic impurities.
AB  - The International Conference on Harmonization (ICH) M7 guidance for the
      assessment and control of DNA reactive impurities in pharmaceutical products
      includes the use of in silico prediction systems as part of the hazard
      identification and risk assessment strategy. This is the first internationally
      agreed guidance document to include the use of these types of approaches. The
      guideline requires the use of two complementary approaches, an expert rule-based
      method and a statistical algorithm. In addition, the guidance states that the
      output from these computer-based assessments can be reviewed using expert
      knowledge to provide additional support or resolve conflicting predictions. This
      approach is designed to maximize the sensitivity for correctly identifying DNA
      reactive compounds while providing a framework to reduce the number of compounds
      that need to be synthesized, purified and subsequently tested in an Ames assay.
      Using a data set of 801 chemicals and pharmaceutical intermediates, we have
      examined the relative predictive performances of some popular commercial in
      silico systems that are in common use across the pharmaceutical industry. The
      overall accuracy of each of these systems was fairly comparable ranging from 68%
      to 73%; however, the sensitivity of each system (i.e. how many Ames positive
      compounds are correctly identified) varied much more dramatically from 48% to
      68%. We have explored how these systems can be combined under the ICH M7 guidance
      to enhance the detection of DNA reactive molecules. Finally, using four smaller
      sets of molecules, we have explored the value of expert knowledge in the review
      process, especially in cases where the two systems disagreed on their
      predictions, and the need for care when evaluating the predictions for large data
      sets. 

PMID- 25980642
TI  - Volcano seismicity and ground deformation unveil the gravity-driven magma
      discharge dynamics of a volcanic eruption.
AB  - Effusive eruptions are explained as the mechanism by which volcanoes restore the
      equilibrium perturbed by magma rising in a chamber deep in the crust. Seismic,
      ground deformation and topographic measurements are compared with effusion rate
      during the 2007 Stromboli eruption, drawing an eruptive scenario that shifts our
      attention from the interior of the crust to the surface. The eruption is modelled
      as a gravity-driven drainage of magma stored in the volcanic edifice with a minor
      contribution of magma supplied at a steady rate from a deep reservoir. Here we
      show that the discharge rate can be predicted by the contraction of the volcano
      edifice and that the very-long-period seismicity migrates downwards, tracking the
      residual volume of magma in the shallow reservoir. Gravity-driven magma discharge
      dynamics explain the initially high discharge rates observed during eruptive
      crises and greatly influence our ability to predict the evolution of effusive
      eruptions. 

PMID- 25980643
TI  - Subcortical gray matter segmentation and voxel-based analysis using transverse
      relaxation and quantitative susceptibility mapping with application to multiple
      sclerosis.
AB  - PURPOSE: To investigate subcortical gray matter segmentation using transverse
      relaxation rate (R2 *) and quantitative susceptibility mapping (QSM) and apply it
      to voxel-based analysis in multiple sclerosis (MS). MATERIALS AND METHODS: Voxel
      based variation in R2 * and QSM within deep gray matter was examined and compared
      to standard whole-structure analysis using 37 MS subjects and 37 matched
      controls. Deep gray matter nuclei (caudate, putamen, globus pallidus, and
      thalamus) were automatically segmented and morphed onto a custom atlas based on
      QSM and standard T1 -weighted images. Segmentation accuracy and scan-rescan
      reliability were tested. RESULTS: When considering only significant regions as
      returned by the multivariate voxel-based analysis, increased R2 * and QSM was
      found in MS subjects compared to controls in portions of all four nuclei studied
      (P < 0.002). For R2 *, regional analysis yielded at least 66-fold improved P
      value significance in all nuclei over standard whole-structure analysis, while
      for QSM only thalamus benefited, with 5-fold improvement in significance.
      Improved segmentation over standard methods, particularly for globus pallidus
      (2.8 times higher Dice score), was achieved by incorporating high-contrast QSM
      into the atlas. Voxel-based reliability was highest for QSM (<1% variation).
      CONCLUSION: Automatic segmentation of iron-rich deep gray matter can be improved
      by incorporating QSM. Voxel-based evaluation yielded increased R2 * and QSM in MS
      subjects in all four nuclei studied with R2 *, benefiting the most from localized
      analysis over whole-structure measures.

PMID- 25980644
TI  - Characterization of microbial siderophores by mass spectrometry.
AB  - Siderophores play important roles in microbial iron piracy, and are applied as
      infectious disease biomarkers and novel pharmaceutical drugs. Inductively coupled
      plasma and molecular mass spectrometry (ICP-MS) combined with high resolution
      separations allow characterization of siderophores in complex samples taking
      advantages of mass defect data filtering, tandem mass spectrometry, and iron
      containing compound quantitation. The enrichment approaches used in siderophore
      analysis and current ICP-MS technologies are reviewed. The recent tools for fast
      dereplication of secondary metabolites and their databases are reported. This
      review on siderophores is concluded with their recent medical, biochemical,
      geochemical, and agricultural applications in mass spectrometry context.

PMID- 25980645
TI  - Putting feet first.

PMID- 25980646
TI  - A guideline for the use of variable rate intravenous insulin infusion in medical
      inpatients.
AB  - The present paper summarizes the key recommendations in a recent publication
      produced by the Joint British Diabetes Societies for Inpatient Care on the use of
      variable rate i.v. insulin infusion in 'medical' inpatients. The full guideline
      is available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_VRIII.pdf and
      is designed to be a practical guide that can used by any healthcare professional
      who manages medical inpatients with hyperglycaemia. Its main aim is to allow
      variable rate i.v. insulin infusion to be used safely, effectively and
      efficiently for this specific group of inpatients. 

PMID- 25980647
TI  - Management of hyperosmolar hyperglycaemic state in adults with diabetes.
AB  - Hyperglycaemic hyperosmolar state (HHS) is a medical emergency, which differs
      from diabetic ketoacidosis (DKA) and requires a different approach. The present
      article summarizes the recent guidance on HHS that has been produced by the Joint
      British Diabetes Societies for Inpatient Care, available in full at
      http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_HHS_Adults.pdf. HHS has a
      higher mortality rate than DKA and may be complicated by myocardial infarction,
      stroke, seizures, cerebral oedema and central pontine myelinolysis and there is
      some evidence that rapid changes in osmolality during treatment may be the
      precipitant of central pontine myelinolysis. Whilst DKA presents within hours of
      onset, HHS comes on over many days, and the dehydration and metabolic
      disturbances are more extreme. The key points in these HHS guidelines include:
      (1) monitoring of the response to treatment: (i) measure or calculate the serum
      osmolality regularly to monitor the response to treatment and (ii) aim to reduce
      osmolality by 3-8 mOsm/kg/h; (2) fluid and insulin administration: (i) use i.v.
      0.9% sodium chloride solution as the principal fluid to restore circulating
      volume and reverse dehydration, (ii) fluid replacement alone will cause a fall in
      blood glucose (BG) level, (iii) withhold insulin until the BG level is no longer
      falling with i.v. fluids alone (unless ketonaemic), (iv) an initial rise in
      sodium level is expected and is not itself an indication for hypotonic fluids and
      (v) early use of insulin (before fluids) may be detrimental; and (3) delivery of
      care: (i) The diabetes specialist team should be involved as soon as possible and
      (ii) patients should be nursed in areas where staff are experienced in the
      management of HHS. 

PMID- 25980650
TI  - Editorial: is ischemic stroke an inflammatory disease?

PMID- 25980649
TI  - Hierarchical process memory: memory as an integral component of information
      processing.
AB  - Models of working memory (WM) commonly focus on how information is encoded into
      and retrieved from storage at specific moments. However, in the majority of real
      life processes, past information is used continuously to process incoming
      information across multiple timescales. Considering single-unit,
      electrocorticography, and functional imaging data, we argue that (i) virtually
      all cortical circuits can accumulate information over time, and (ii) the
      timescales of accumulation vary hierarchically, from early sensory areas with
      short processing timescales (10s to 100s of milliseconds) to higher-order areas
      with long processing timescales (many seconds to minutes). In this hierarchical
      systems perspective, memory is not restricted to a few localized stores, but is
      intrinsic to information processing that unfolds throughout the brain on multiple
      timescales. 

PMID- 25980651
TI  - Editorial: effect of statins on rates of long-term cardiovascular events and
      restenosis following carotid endarterectomy.

PMID- 25980652
TI  - Editorial: oxidative stress in pathophysiological conditions.

PMID- 25980653
TI  - Korean red ginseng extract rejuvenates testicular ineffectiveness and sperm
      maturation process in aged rats by regulating redox proteins and oxidative
      defense mechanisms.
AB  - Distortion of intracellular oxidant and antioxidant balances appears to be a
      common feature that underlies in age-related male sexual impairment. Therefore
      regulating oxidative defense mechanisms might be an ideal approach in improving
      male sexual dysfunctions. In the present study, the effect of Korean red ginseng
      aqueous extract (KRG) on age-induced testicular dysfunction in rats was
      investigated. KRG (200mg/kg) mixed with regular pellet diet was administered
      orally for six months and the morphological, spermatogenic and antioxidant enzyme
      status in testis of aged rats (18months) were evaluated. Data indicated a
      significant change in morphology and decrease in spermatogenesis-related
      parameters in aged rats (AC) compared with young rats (YC). Sperm number, germ
      cell count, Sertoli cell count and Sertoli cell index were significantly (p<0.05)
      restored in KRG-treated aged rat groups (G-AC). Further the increased lipid
      peroxidation as measured by malondialdehyde (p<0.05), and altered enzymatic
      (superoxide dismutase, glutathione peroxidase, glutathione S-transferase,
      glutathione reductase and catalase) and non-enzymatic (reduced glutathione,
      ascorbic acid and alpha-tocopherol) antioxidants (p<0.05) were attenuated by KRG
      treatment in aged rats to near normal levels as in YC groups. Furthermore,
      proteomic analysis demonstrated differential expression of selected proteins such
      as phosphatidylinositol transfer protein, fatty acid binding protein-9,
      triosephosphate isomerase-1 and aldehyde (aldose) reductase-1in aged rats was
      significantly (p<0.05) protected by KRG treatment. In conclusion, long-term
      administration of KRG restored aging-induced testicular ineffectiveness in rats
      by modulating redox proteins and oxidative defense mechanisms. 

PMID- 25980654
TI  - Zinc oxide nanoparticles induced cyto- and genotoxicity in kidney epithelial
      cells.
AB  - The wide uses of zinc oxide nanoparticles (nano-ZnO) in industrial, cosmetics,
      medicine, food production and electronics associate with increase in occupational
      and public exposure. Although, toxicity of nano-ZnO has been extensively studied
      on many different cell types and animal systems, there is a significant lack of
      toxicological data focus on nephrotoxic potential of nano-ZnO. In this study, the
      cyto- and genotoxic effects of nano-ZnO on rat kidney epithelial cells (NRK-52E)
      were investigated by using different assays. Nano-ZnO (10-50 nm of sizes) were
      synthesized by sol-gel method. For the cytotoxic effect of nano-ZnO, mean of
      inhibition concentration (IC50) values in cell line was evaluated by MTT, Trypan
      Blue (TB) and Neutral Red Uptake (NRU) assays at 25.0-100.0 MUg/mL exposure
      concentrations. Nano-ZnO showed cytotoxic activity by acting on different targets
      in renal cells, with IC50 >= 73.05 MUg/mL. Comet assay was used to evaluate the
      genotoxicity of nano-ZnO (12.5-50.0 MUg/mL). Nano-ZnO caused statistically
      significant DNA damage. Our results highlight the important risk of cyto- and
      genotoxic effects of nano-ZnO over the kidney.

PMID- 25980655
TI  - Cell cycle arrest and apoptogenic properties of opium alkaloids noscapine and
      papaverine on breast cancer stem cells.
AB  - Previous report of the vast effectiveness of opium derivatives in cancer therapy
      is leading us to see possible effects of these derivatives on cancer stem cells
      in order to find new agent for cancer therapy. In this study, cells were stained
      for CSC markers and sorted by magnetic beads. CSCs exhibit the characteristic
      CD44(+)/CD24(-/low)/ESA(+) phenotype. Noscapine and papaverine (alkaloids) showed
      anti-proliferative activity on MCF-7 and MDA-MB-231 cell lines. It was observed
      that noscapine has more cytotoxic effect on CSC derived from both cell lines
      compared with their parental cells. Papaverine has more cytotoxic effect on MCF-7
      CSCs in comparison with parental cells, while CSCs population of MDA-MB-231 is
      more resistant to papaverine compared with MDA-MB-231 cells. Noscapine enhances
      apoptosis in MDA-MB-231 CSCs more than parent cells, while in MCF-7 CSCs the
      apoptosis is less than parent cells. Our results show that papverine is less
      active in terms of apoptotic effect on CSCs in both cell lines. Moreover,
      noscapine arrests MCF-7 and MDA-MB-231 CSCs cell cycle at G2/M phase, while
      papverine arrests cell cycle at G0/G1 phase. It was suggested different mechanism
      for apoptotic cytotoxicity. The results of this study show possible specific
      effects of noscapine on these breast cell lines CSCs. 

PMID- 25980656
TI  - The Health Beliefs of Migrant Farmworker Parents: An Ethnographic Exploration.
AB  - The purpose of this study was to explore the health beliefs of migrant
      farmworkers parents by approaching and interviewing the sample population in a
      health clinic where they seek care for their children. It is impossible to plan,
      implement care, or create health care delivery models without knowledge of health
      beliefs. An understanding of parental health beliefs in the vulnerable population
      of migrant farmworkers will assure a more informed approach to health matters of
      their children, while also improving health care delivery and providing
      culturally specific health care models. Collecting data in locations historically
      proven to generate trust and respect supported the objectives of this research
      study and promoted direct engagement with a group that is often misunderstood and
      marginalized. Twenty migrant farmworkers parents were interviewed during growing
      season in the largely agricultural setting of Weld County, Colorado. Associated
      variables/phenomena determining health beliefs include parental decision-making
      regarding children's health maintenance, injury prevention, and health care. The
      overarching theme that emerged from the data was pride in having healthy children
      with major themes of respect, convenience and inhibition/suppression.

PMID- 25980657
TI  - Biochar amendment to soil changes dissolved organic matter content and
      composition.
AB  - Amendments of biochar, a product of pyrolysis of biomass, have been shown to
      increase fertility of acidic soils by enhancing soil properties such as pH,
      cation-exchange-capacity and water-holding-capacity. These parameters are
      important in the context of natural organic matter contained in soils, of which
      dissolved organic matter (DOM) is the mobile and most bioavailable fraction. The
      effect of biochar on the content and composition of DOM in soils has received
      little research attention. This study focuses on the effects of amendments of two
      different biochars to an acidic acrisol and a pH-neutral brown soil. A batch
      experiment showed that mixing biochar with the acrisols at a 10 wt.% dose
      increased the pH from 4.9 to 8.7, and this resulted in a 15-fold increase in the
      dissolved organic carbon concentration (from 4.5 to 69 mg L(-1)). The pH-increase
      followed the same trend as the release of DOM in the experiment, causing higher
      DOM solubility and desorption of DOM from mineral sites. The binding to biochar
      of several well-characterised reference DOM materials was also investigated and
      results showed a higher sorption of aliphatic DOM to biochar than aromatic DOM,
      with DOM-water partitioning coefficients (Kd-values) ranging from 0.2 to 590 L
      kg(-1). A size exclusion occurring in biochar's micropores, could result in a
      higher sorption of smaller aliphatic DOM molecules than larger aromatic ones.
      These findings indicate that biochar could increase the leaching of DOM from
      soil, as well as change the DOM composition towards molecules with a larger size
      and higher aromaticity.

PMID- 25980658
TI  - Total cyanide mass measurement with micro-ion selective electrode for
      determination of specific activity of carbon-11 cyanide.
AB  - In this research, we aim to directly measure the specific activity (SA) of the
      carbon-11 cyanide ([(11)C]CN-) produced by our in-house built automated
      [(11)C]HCN production system and to identify the major sources of (12)C-cyanide
      ((12)CN-). The [(11)C]CN- is produced from [(11)C]CO2, which is generated by the
      (14)N(p,alpha)(11)C nuclear reaction using a cyclotron. Direct measurement of
      cyanide concentrations was accomplished using a relatively inexpensive, and easy
      to use ion selective electrode (ISE) which offered an appropriate range of
      sensitivity for detecting mass. Multiple components of the [(11)C]HCN production
      system were isolated in order to determine their relative contributions to (12)CN
      mass. It was determined that the system gases were responsible for approximately
      30% of the mass, and that the molecular sieve/nickel furnace unit contributed
      approximately 70% of the mass. Beam on target (33uA for 1 and 10min) did not
      contribute significantly to the mass. Additionally, we compared the SA of our
      [(11)C]HCN precursor determined using the ISE to the SA of our current [(11)C]CN-
      derived radiotracers determined by HPLC to assure there was no significant
      difference between the two methods. These results are the first reported use of
      an ion selective electrode to determine the SA of no-carrier-added cyanide ion,
      and clearly show that it is a valuable, inexpensive and readily available tool
      suitable for this purpose. 

PMID- 25980659
TI  - Thermoluminescence and photoluminescence analyses of MEH-PPV, MDMO-PPV and
      RU(bpy)3 gamma-irradiated polymer thin films.
AB  - Effects of irradiation with (60)Co gamma photons on poly[2-methoxy-5-(2
      ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), poly[2-methoxy-5-(3',7'
      dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) and tris(2,2'
      bipyridyl)dichlororuthenium(II) hexahydrate (Ru(bpy)3) thin films were analyzed
      regarding their thermoluminescence (TL) and photoluminescence (PL) properties. A
      linear TL dose response was obtained from the MEH-PPV and MDMO-PPV polymer films
      in dose ranges of approximately 0.170-4.08kGy and 0.170-0.850kGy, respectively,
      followed by a supralinear behavior. A dependence on the conjugation length of the
      polymer chains which was favored by heating of the film, was observed, and
      irradiation generated a blue-shift in MEH-PPV and Ru(bpy)3. Furthermore, the PL
      structure was not modified. The most likely effect involved in the TL emission
      was trapping. The high activation energy values of the traps in the TL may be
      attributed in part to the binding energy of the exciton. A deconvolution process
      was carried out to obtain the kinetic parameters from the TL glow curves and PL
      spectra. 

PMID- 25980661
TI  - Barcoding of fresh water fishes from Pakistan.
AB  - DNA bar-coding is a taxonomic method that uses small genetic markers in
      organisms' mitochondrial DNA (mt DNA) for identification of particular species.
      It uses sequence diversity in a 658-base pair fragment near the 5' end of the
      mitochondrial cytochrome c oxidase subunit 1 (CO1) gene as a tool for species
      identification. DNA barcoding is more accurate and reliable method as compared
      with the morphological identification. It is equally useful in juveniles as well
      as adult stages of fishes. The present study was conducted to identify three farm
      fish species of Pakistan (Cyprinus carpio, Cirrhinus mrigala, and
      Ctenopharyngodon idella) genetically. All of them belonged to family cyprinidae.
      CO1 gene was amplified. PCR products were sequenced and analyzed by bioinformatic
      software. Conspecific, congenric, and confamilial k2P nucleotide divergence was
      estimated. From these findings, it was concluded that the gene sequence, CO1, may
      serve as milestone for the identification of related species at molecular level.

PMID- 25980662
TI  - Complete sequence and gene organization of the mitochondrial genome of Asio
      flammeus (Strigiformes, strigidae).
AB  - The complete sequence of the mitochondrial genome was determined for Asio
      flammeus, which is distributed widely in geography. The length of the complete
      mitochondrial genome was 18,966 bp, containing 2 rRNA genes, 22 tRNA genes, 13
      protein-coding genes (PCGs), and 1 non-coding region (D-loop). All the genes were
      distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes
      which were encoded on the L-strand. The D-loop of A. flammeus contained many
      tandem repeats of varying lengths and repeat numbers. The molecular-based
      phylogeny showed that our species acted as the sister group to A. capensis and
      the supported Asio was the monophyletic group.

PMID- 25980663
TI  - Lessons in every patient encounter.

PMID- 25980660
TI  - High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic
      Patients After Cardiothoracic Surgery: A Randomized Clinical Trial.
AB  - IMPORTANCE: Noninvasive ventilation delivered as bilevel positive airway pressure
      (BiPAP) is often used to avoid reintubation and improve outcomes of patients with
      hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is
      increasingly used to improve oxygenation because of its ease of implementation,
      tolerance, and clinical effectiveness. OBJECTIVE: To determine whether high-flow
      nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute
      respiratory failure after cardiothoracic surgery. DESIGN AND SETTING:
      Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between
      June 15, 2011, and January 15, 2014, at 6 French intensive care units.
      PARTICIPANTS: A total of 830 patients who had undergone cardiothoracic surgery,
      of which coronary artery bypass, valvular repair, and pulmonary
      thromboendarterectomy were the most common, were included when they developed
      acute respiratory failure (failure of a spontaneous breathing trial or successful
      breathing trial but failed extubation) or were deemed at risk for respiratory
      failure after extubation due to preexisting risk factors. INTERVENTIONS: Patients
      were randomly assigned to receive high-flow nasal oxygen therapy delivered
      continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen
      [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4
      hours per day (pressure support level, 8 cm H2O; positive end-expiratory
      pressure, 4 cm H2O; FiO2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES: The primary
      outcome was treatment failure, defined as reintubation, switch to the other study
      treatment, or premature treatment discontinuation (patient request or adverse
      effects, including gastric distention). Noninferiority of high-flow nasal oxygen
      therapy would be demonstrated if the lower boundary of the 95% CI were less than
      9%. Secondary outcomes included mortality during intensive care unit stay,
      changes in respiratory variables, and respiratory complications. RESULTS: High
      flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87
      of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416
      patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P
      = .003). No significant differences were found for intensive care unit mortality
      (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%];
      P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was
      significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%
      13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE: Among cardiothoracic
      surgery patients with or at risk for respiratory failure, the use of high-flow
      nasal oxygen therapy compared with intermittent BiPAP did not result in a worse
      rate of treatment failure. The findings support the use of high-flow nasal oxygen
      therapy in similar patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01458444.

PMID- 25980664
TI  - Can Helical Peptides Unwind One Turn at a Time? - Controlled Conformational
      Transitions in alpha,beta(2,3)-Hybrid Peptides.
AB  - Unfolding of helical trans-beta(2,3) -hybrid peptides with (alpha-beta)n alpha
      composition, when executed by increasing solvent polarity or temperature,
      proceeded in a systematic manner with the turns unwinding sequentially; C
      terminal region of these peptides were first to unwind and the process propagated
      towards N terminus with more and more beta residues equilibrating from the gauche
      to the anti rotameric state across Calpha-Cbeta . This is evidenced by clear
      change in their Cbeta H signal splitting, (3)JCalphaH-CbetaH values, and
      sequential disappearance of i,i+2 NOEs.

PMID- 25980665
TI  - The Drosophila ortholog of the Zc3h14 RNA binding protein acts within neurons to
      pattern axon projection in the developing brain.
AB  - The dNab2 polyadenosine RNA binding protein is the D. melanogaster ortholog of
      the vertebrate ZC3H14 protein, which is lost in a form of inherited intellectual
      disability (ID). Human ZC3H14 can rescue D. melanogaster dNab2 mutant phenotypes
      when expressed in all neurons of the developing nervous system, suggesting that
      dNab2/ZC3H14 performs well-conserved roles in neurons. However, the cellular and
      molecular requirements for dNab2/ZC3H14 in the developing nervous system have not
      been defined in any organism. Here we show that dNab2 is autonomously required
      within neurons to pattern axon projection from Kenyon neurons into the mushroom
      bodies, which are required for associative olfactory learning and memory in
      insects. Mushroom body axons lacking dNab2 project aberrantly across the brain
      midline and also show evidence of defective branching. Coupled with the prior
      finding that ZC3H14 is highly expressed in rodent hippocampal neurons, this
      requirement for dNab2 in mushroom body neurons suggests that dNab2/ZC3H14 has a
      conserved role in supporting axon projection and branching. Consistent with this
      idea, loss of dNab2 impairs short-term memory in a courtship conditioning assay.
      Taken together these results reveal a cell-autonomous requirement for the dNab2
      RNA binding protein in mushroom body development and provide a window into
      potential neurodevelopmental functions of the human ZC3H14 protein.

PMID- 25980666
TI  - Encapsulation of 10-hydroxy camptothecin in supramolecular hydrogel as an
      injectable drug delivery system.
AB  - 10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific
      chemotherapeutic agent, which is a necessary choice to inhibit tumor residue
      growth and prevent tumor metastasis after surgery. But it suffers from light
      decomposition, poor solubility, relatively low bioavailability, and some side
      effects, which are the major obstacles toward its clinical use. Integration of
      hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the
      disadvantageous situation of HCPT. In this study, a novel supramolecular
      hydrogelator with improved synthetic strategy was triggered by chemical
      hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high
      equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was
      utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels
      were characterized by several techniques including transmission electronic
      microscopy, rheology, and UV spectroscopy. In vitro release experiment indicated
      HCPT hydrogel could maintain long term and sustained release of HCPT at high
      accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides,
      with prominent physical properties of carrier, HCPT hydrogel possessed
      satisfactory stability, syringeability, and recoverability, demonstrating itself
      as a potential localized injectable drug delivery system.

PMID- 25980667
TI  - Pharmacogenetics of treatment response in psoriatic arthritis.
AB  - TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs
      (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly
      prescribed treatments in psoriatic arthritis. A large proportion of patients do
      not respond to these medications, although unfortunately clinically useful
      biomarkers that predict future response are currently lacking. Several candidate
      gene polymorphisms have been associated with responses to biologic therapies and
      nbDMARDs; however, replication and validation of these variants in large
      prospective psoriatic arthritis cohorts are required before translating these to
      clinical practice. In this review, we discuss the advances made in
      pharmacogenetics of treatment response in psoriatic arthritis to date, with focus
      on biologic therapies approved for use, nbDMARDs and NSAIDs, as well as outline
      emerging methodologies to obtain data that will help inform a future precision
      medicine approach in this condition. 

PMID- 25980669
TI  - One-Step Formation of "Chain-Armor"-Stabilized DNA Nanostructures.
AB  - DNA-based self-assembled nanostructures are widely used to position organic and
      inorganic objects with nanoscale precision. A particular promising application of
      DNA structures is their usage as programmable carrier systems for targeted drug
      delivery. To provide DNA-based templates that are robust against degradation at
      elevated temperatures, low ion concentrations, adverse pH conditions, and DNases,
      we built 6-helix DNA tile tubes consisting of 24 oligonucleotides carrying alkyne
      groups on their 3'-ends and azides on their 5'-ends. By a mild click reaction,
      the two ends of selected oligonucleotides were covalently connected to form rings
      and interlocked DNA single strands, so-called DNA catenanes. Strikingly, the
      structures stayed topologically intact in pure water and even after precipitation
      from EtOH. The structures even withstood a temperature of 95  degrees C when all
      of the 24 strands were chemically interlocked. 

PMID- 25980668
TI  - Voltage-dependent calcium channels in chondrocytes: roles in health and disease.
AB  - Chondrocytes, the single cell type in adult articular cartilage, have
      conventionally been considered to be non-excitable cells. However, recent
      evidence suggests that their resting membrane potential (RMP) is less negative
      than that of excitable cells, and they are fully equipped with channels that
      control ion, water and osmolyte movement across the chondrocyte membrane. Amongst
      calcium-specific ion channels, members of the voltage-dependent calcium channel
      (VDCC) family are expressed in chondrocytes where they are functionally active. L
      type VDCC inhibitors such as nifedipine and verapamil have contributed to our
      understanding of the roles of these ion channels in chondrogenesis, chondrocyte
      signalling and mechanotransduction. In this narrative review, we discuss
      published data indicating that VDCC function is vital for chondrocyte health,
      especially in regulating proliferation and maturation. We also highlight the fact
      that activation of VDCC function appears to accompany various inflammatory
      aspects of osteoarthritis (OA) and, based on in vitro data, the application of
      nifedipine and/or verapamil may be a promising approach for ameliorating OA
      severity. However, very few studies on clinical outcomes are available regarding
      the influence of calcium antagonists, which are used primarily for treating
      cardiovascular conditions in OA patients. This review is intended to stimulate
      further research on the chondrocyte 'channelome', contribute to the development
      of novel therapeutic strategies and facilitate the retargeting and repositioning
      of existing pharmacological agents currently used for other comorbidities for the
      treatment of OA. 

PMID- 25980670
TI  - Asymptotic efficiency of the pseudo-maximum likelihood estimator in multi-group
      factor models with pooled data.
AB  - A multi-group factor model is suitable for data originating from different
      strata. However, it often requires a relatively large sample size to avoid
      numerical issues such as non-convergence and non-positive definite covariance
      matrices. An alternative is to pool data from different groups in which a single
      group factor model is fitted to the pooled data using maximum likelihood. In this
      paper, properties of pseudo-maximum likelihood (PML) estimators for pooled data
      are studied. The pooled data are assumed to be normally distributed from a single
      group. The resulting asymptotic efficiency of the PML estimators of factor
      loadings is compared with that of the multi-group maximum likelihood estimators.
      The effect of pooling is investigated through a two-group factor model. The
      variances of factor loadings for the pooled data are underestimated under the
      normal theory when error variances in the smaller group are larger.
      Underestimation is due to dependence between the pooled factors and pooled error
      terms. Small-sample properties of the PML estimators are also investigated using
      a Monte Carlo study.

PMID- 25980671
TI  - Variability of 4-Monomethylsterols and 4,4'-Dimethylsterols in Olive Oil and
      Their Use as Indicators of Olive Variety, Ripening Degree, and Oil Storage
      Temperature.
AB  - To investigate the variability of 4-monomethylsterols and 4,4'-dimethylsterols in
      olive oil as a result of variety, ripening, and storage temperature, 36 samples
      were subjected to gas chromatography with flame ionization detection (GC-FID) and
      with mass spectrometric detection (GC-MS), and results were processed by
      univariate and multivariate statistics. Relative amounts (percent) of beta
      amyrin, cycloartenol, and 24-methylenecycloartanol accounted for the most
      variation due to variety, while citrostadienol (percent) and 24
      methylenecycloartanol (milligrams per 100 g) were strongly affected by ripening.
      Multivariate statistics differentiated olive oils regardless of storage
      conditions, which implied the possibility to use 4-monomethyl- and 4,4'
      dimethylsterols as indicators of variety and ripening degree for fresh and stored
      oils. Absolute changes in 4-monomethyl- and 4,4'-dimethylsterols after storage
      were of a much smaller magnitude, meaning the investigated olive oils essentially
      retained health-beneficial features that derive from these compounds. Relative
      changes caused by storage were specific for each storage temperature and were
      useful in discriminating oils by linear discriminant analysis. 

PMID- 25980673
TI  - Study of molecule variations in human xanthelasma skin based on confocal micro
      raman spectroscopy.
AB  - Confocal micro-Raman spectroscopy was used to distinguish human xanthelasma skin
      (HXS) from the human normal skin (HNS). Results showed that intensive Raman peaks
      at 1,269, 1,336, 1,448, and 1,656 cm(-1) increased obviously. Both 1,269 and
      1,656 cm(-1) peaks showed that the proteins in HXS were mostly in the anti
      parallel beta sheet conformation. While the intensities of bands at 1,032, 1,087,
      1,300, and 1,448 cm(-1) belonged to lipids were enhanced in HXS spectrum compared
      to those in HNS spectrum. There were main intercellular lipids alkyl chains with
      minor proteins contribution at 1,087 cm(-1) and phenylalanine at 1,032 cm(-1) .
      To quantitative analysis of the difference, the ratio of I852/I829 was
      calculated, which was 1:1.04 +/- 0.04 and 1:1.11 +/- 0.02 for HNS and HXS (p <
      0.01), respectively. The data indicated that some tyrosine residues, which form a
      hydrogen bond with H2 O prior to aggregation, were captured by strong hydrogen
      bond acceptors in the aggregate. The decreased ratio of I852/I829 indicated more
      hydrophobic in HXS than HNS. Principal component analysis showed a one-to-one
      relationship between human xanthelasma skin and the corresponding Raman spectra.
      It could be given useful help for the diagnostication of xanthelasma.

PMID- 25980672
TI  - A systems-biological study on the identification of safe and effective molecular
      targets for the reduction of ultraviolet B-induced skin pigmentation.
AB  - Melanogenesis is the process of melanin synthesis through keratinocytes
      melanocytes interaction, which is triggered by the damaging effect of ultraviolet
      B (UVB) rays. It is known that melanogenesis influences diverse cellular
      responses, including cell survival and apoptosis, via complex mechanisms of
      feedback and crosstalk. Therefore, an attempt to suppress melanin production by
      modulating the melanogenesis pathway may induce perturbations in the apoptotic
      balance of the cells in response to UVB irradiation, which results in various
      skin diseases such as melasma, vitiligo, and skin cancer. To identify such
      appropriate target strategies for the reduction of UVB-induced melanin synthesis,
      we reconstructed the melanogenesis signaling network and developed a Boolean
      network model. Mathematical simulations of the melanogenesis network model
      revealed that the inhibition of beta-catenin in the melanocytes effectively
      reduce melanin production while having minimal influence on the apoptotic balance
      of the cells. Exposing cells to a beta-catenin inhibitor decreased pigmentation
      but did not significantly change the B-cell Chronic lymphocytic leukemia/lymphoma
      2 expression, a potent regulator of apoptotic balance. Thus, our systems analysis
      suggests that the inhibition of beta-catenin may be the most appropriate target
      strategy for the reduction of UVB-induced skin pigmentation. 

PMID- 25980675
TI  - Detecting overlapping instances in microscopy images using extremal region trees.
AB  - In many microscopy applications the images may contain both regions of low and
      high cell densities corresponding to different tissues or colonies at different
      stages of growth. This poses a challenge to most previously developed automated
      cell detection and counting methods, which are designed to handle either the low
      density scenario (through cell detection) or the high-density scenario (through
      density estimation or texture analysis). The objective of this work is to detect
      all the instances of an object of interest in microscopy images. The instances
      may be partially overlapping and clustered. To this end we introduce a tree
      structured discrete graphical model that is used to select and label a set of non
      overlapping regions in the image by a global optimization of a classification
      score. Each region is labeled with the number of instances it contains - for
      example regions can be selected that contain two or three object instances, by
      defining separate classes for tuples of objects in the detection process. We show
      that this formulation can be learned within the structured output SVM framework
      and that the inference in such a model can be accomplished using dynamic
      programming on a tree structured region graph. Furthermore, the learning only
      requires weak annotations - a dot on each instance. The candidate regions for the
      selection are obtained as extremal region of a surface computed from the
      microscopy image, and we show that the performance of the model can be improved
      by considering a proxy problem for learning the surface that allows better
      selection of the extremal regions. Furthermore, we consider a number of
      variations for the loss function used in the structured output learning. The
      model is applied and evaluated over six quite disparate data sets of images
      covering: fluorescence microscopy, weak-fluorescence molecular images, phase
      contrast microscopy and histopathology images, and is shown to exceed the state
      of the art in performance. 

PMID- 25980674
TI  - Cytokine profiles in interstitial fluid from chronic atopic dermatitis skin.
AB  - BACKGROUND: The in vivo levels of inflammatory mediators in chronic atopic
      dermatitis (AD) skin are not well-defined due to the lack of a non-invasive or
      minimally invasive sampling technique. OBJECTIVES: To investigate the cytokine
      milieu in interstitial fluid (ISF) collected from chronic lesional AD skin as
      compared to ISF from non-lesional AD skin and/or healthy donor skin. METHODS: ISF
      was obtained using a minimally invasive technique of creating micropores in the
      skin by a laser, and harvesting ISF through aspiration. We determined the levels
      of 33 cytokines by Luminex and ELISA in ISF and plasma from sixteen AD patients
      and twelve healthy individuals. In seven AD patients, we analysed the IL-13, IL
      31, IL-17, IL-22 and IFN-gamma production by T cells isolated from lesional skin.
      AD patients were genotyped for the filaggrin gene (FLG)-null mutations 2282del4,
      R501X, R2447X and S3247X. RESULTS: Twenty-five of 33 examined mediators were
      detected in the ISF. The levels of IL-1alpha, IL-1beta, IL-18, IL-1RA, IL-5, IL
      13, IL-6, IL-8, TNF-alpha, RANTES(CCL-5), MIG(CXCL-9), IP-10(CXCL-10), TARC(CCL
      17), VEGF and G-CSF showed significant differences between either lesional, non
      lesional and/or healthy skin. IP-10 levels in ISF from lesional and non-lesional
      AD skin showed significant correlation with IP-10 blood levels. IP-10 also showed
      a significant correlation with clinical severity (SCORAD), as did IL-13. Levels
      of both IP-10 and IL-13 were more pronounced in patients with FLG-null mutations.
      Furthermore, FLG-null mutation carriers had more severe AD. CONCLUSION: The
      presented minimally invasive technique is a valuable tool to determine the in
      vivo cytokine profile of AD skin.

PMID- 25980676
TI  - Splines for diffeomorphisms.
AB  - This paper develops a method for higher order parametric regression on
      diffeomorphisms for image regression. We present a principled way to define
      curves with nonzero acceleration and nonzero jerk. This work extends methods
      based on geodesics which have been developed during the last decade for
      computational anatomy in the large deformation diffeomorphic image analysis
      framework. In contrast to previously proposed methods to capture image changes
      over time, such as geodesic regression, the proposed method can capture more
      complex spatio-temporal deformations. We take a variational approach that is
      governed by an underlying energy formulation, which respects the nonflat geometry
      of diffeomorphisms. Such an approach of minimal energy curve estimation also
      provides a physical analogy to particle motion under a varying force field. This
      gives rise to the notion of the quadratic, the cubic and the piecewise cubic
      splines on the manifold of diffeomorphisms. The variational formulation of
      splines also allows for the use of temporal control points to control spline
      behavior. This necessitates the development of a shooting formulation for
      splines. The initial conditions of our proposed shooting polynomial paths in
      diffeomorphisms are analogous to the Euclidean polynomial coefficients. We
      experimentally demonstrate the effectiveness of using the parametric curves both
      for synthesizing polynomial paths and for regression of imaging data. The
      performance of the method is compared to geodesic regression. 

PMID- 25980677
TI  - Dendritic nanocarriers based on hyperbranched polymers.
AB  - Hyperbranched polymers are obtained through one-step polymerization reactions and
      exhibit properties that are very similar to those of perfect dendrimer analogues.
      Therefore, hyperbranched polymers are a suitable alternative for perfect
      dendrimers as building blocks for dendritic nanocarrier systems. With regard to
      using soluble hyperbranched polymers as carrier systems, their flexible chains
      are a major benefit as they can adopt and compartment guest molecules. Upon
      encapsulation, the properties of the host decides the fate of the guest, e.g.,
      solubility, but the host can also shield a guest from the environment and protect
      it, e.g., from degradation and deactivation. With regard to the advantages of
      using hyperbranched polymers as nanocarrier systems and their scalable synthesis,
      we will discuss different types of hyperbranched polymers and their application
      as nanocarrier systems for drugs, dyes, and other guest molecules. 

PMID- 25980679
TI  - A novel role of the checkpoint kinase ATR in leptin signaling.
AB  - In a world with increasing incidences of obesity, it becomes critical to
      understand the detailed regulation of appetite. To identify novel regulators of
      the signaling mediated by one of the key hormones of energy homeostasis, leptin,
      we screened a set of compounds for their effect on the downstream Signal
      Transducer and Activator of Transcription 3 (STAT3) signaling. Interestingly,
      cells exposed to inhibitors of the Ataxia Telangiectasia and RAD3-related protein
      ATR increased their leptin dependent STAT3 activity. This was due to failure of
      the cells to induce the negative feedback mediator Suppressor of Cytokine
      Signaling 3 (SOCS3), suggesting that ATR has a previously unknown role in the
      negative feedback regulation of leptin signaling. This is an important finding
      not only because it sheds light on additional genes involved in leptin signaling,
      but also because it brings forward a new potential therapeutic intervention point
      for increasing leptin signaling in obese individuals. 

PMID- 25980678
TI  - Transfer of the human NKG2D ligands UL16 binding proteins (ULBP) 1-3 is related
      to lytic granule release and leads to ligand retransfer and killing of ULBP
      recipient natural killer cells.
AB  - After immune interactions, membrane fragments can be transferred between cells.
      This fast transfer of molecules is transient and shows selectivity for certain
      proteins; however, the constraints underlying acquisition of a protein are
      unknown. To characterize the mechanism and functional consequences of this
      process in natural killer (NK) cells, we have compared the transfer of different
      NKG2D ligands. We show that human NKG2D ligands can be acquired by NK cells with
      different efficiencies. The main findings are that NKG2D ligand transfer is
      related to immune activation and receptor-ligand interaction and that NK cells
      acquire these proteins during interactions with target cells that lead to
      degranulation. Our results further demonstrate that NK cells that have acquired
      NKG2D ligands can stimulate activation of autologous NK cells. Surprisingly, NK
      cells can also re-transfer the acquired molecule to autologous effector cells
      during this immune recognition that leads to their death. These data demonstrate
      that transfer of molecules occurs as a consequence of immune recognition and
      imply that this process might play a role in homeostatic tuning-down of the
      immune response or be used as marker of interaction. 

PMID- 25980680
TI  - Differences in B7 and CD28 family gene expression in the peripheral blood between
      newly diagnosed young-onset and adult-onset type 1 diabetes patients.
AB  - Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are
      pathogenetic differences between young- and adult-onset T1D patients. We
      hypothesized that the expressions of genes involved in costimulatory immune
      system pathways in peripheral blood are differently regulated in young- and adult
      onset T1D. Study group I consisted of 80 children, adolescents, and young adults
      (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted
      of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA
      expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF
      beta, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic
      polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4;
      rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were
      analyzed. In group I, there was significantly lower expression of CD226 in T1D
      patients than in the controls. In group II, there were significantly higher
      expression levels of CD86 and TGF-beta in T1D patients than in the controls. In
      the T1D patients in group I, the upregulated CD80 expression correlated with the
      expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in
      group II, upregulated CD86 correlated with TGF-beta and CD25. In group I, the
      inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation
      CD86-CD28 pathway and TGF-beta production were activated. These results emphasize
      the differences between young-onset and adult-onset T1D in the regulation of
      costimulatory pathways. These differences should be considered when developing
      novel treatments for T1D. 

PMID- 25980681
TI  - Pre-treatment blood inflammatory markers as predictors of systemic infection
      during induction chemotherapy: results of an exploratory study in patients with
      acute myeloid leukemia.
AB  - PURPOSE: The purpose of this study is to evaluate the role of C-reactive protein
      (CRP) and ferritin blood levels in predicting the incidence of systemic infection
      among adult patients with acute myeloid leukemia (AML) treated with induction
      chemotherapy. METHODS: Adult patients with newly diagnosed AML who were initially
      treated with conventional 3 + 7 induction chemotherapy within 5 days of their
      diagnosis were included. Patients with previous cytotoxic chemotherapy <3 years,
      acute promyelocytic leukemia diagnosis, human immunodeficiency virus infection,
      or significant systemic infection at the time of diagnosis were excluded.
      Patients were treated with an institutional policy of substantial identity with
      negligible differences regarding supportive care. RESULTS: Among 110 patients
      (median age 54.5 years), 39 infectious events in 38 patients were reported, along
      with 21 episodes of infectious treatment-related mortality (TRM; 19.1%). Elevated
      pre-treatment CRP (p = 0.032) and ferritin (p = 0.002) were related to the
      incidence of systemic infection. The degree of increase of blood CRP and ferritin
      level was correlated with the extent of leukocytosis. However, patients with
      elevated inflammatory markers above normal range had increased risk of infection
      irrespective of whether they had leukocytosis or not, suggesting that expansion
      of leukemic blast is another factor affecting the elevation of the markers
      independent to infection propensity and therefore the magnitude of the elevation
      does not quantitatively predict the risk of infection. CONCLUSIONS: Modest
      elevation of baseline blood inflammatory markers above the normal range could be
      an indicator for predicting the incidence of systemic infection in patients with
      AML.

PMID- 25980682
TI  - Curcumin induces ER stress-mediated apoptosis through selective generation of
      reactive oxygen species in cervical cancer cells.
AB  - Prolonged accumulation of misfolded or unfolded proteins caused by cellular
      stress, including oxidative stress, induces endoplasmic reticulum stress, which
      then activates an unfolded protein response (UPR). ER stress is usually
      maintained at higher levels in cancer cells as compared to normal cells due to
      altered metabolism in cancer. Here, we investigated whether curcumin is ER stress
      mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are
      involved in the process as an upstream contributor. Curcumin inhibited
      proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced
      apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK,
      IRE-1alpha, and ATF6, and their downstream-signaling proteins in cervical cancer
      cells, but not in normal epithelial cells and peripheral blood mononuclear cells
      (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also
      activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2
      to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic
      population of cervical cancer cells. Furthermore, curcumin elevated levels of
      intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in
      normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and
      partially restored cell viability in curcumin-treated cancer cells. Collectively,
      these observations show that curcumin promotes ER stress-mediated apoptosis in
      cervical cancer cells through increase of cell type-specific ROS generation.
      Therefore, modulation of these differential responses to curcumin between normal
      and cervical cancer cells could be an effective therapeutic strategy without
      adverse effects on normal cells.

PMID- 25980683
TI  - Clinical performance of seven prescreening tools for osteoporosis in Iranian
      postmenopausal women.
AB  - This study was designed to evaluate seven prescreening osteoporosis models in
      postmenopausal Iranian women. This study was performed on 8644 postmenopausal
      women who have been referred for bone mineral densitometry (BMD) in BMD center of
      Shariati hospital in Tehran between 2001 and 2011. Diagnostic properties of seven
      prescreening instruments were evaluated. With regard to area under curve (AUC),
      these models have low accuracy (AUC <= 0.65). Considering only femoral neck or
      total femur area, these models had low accuracy but were more sensitive. Except
      for three models with sensitivities of <=65 % in both osteoporosis and fracture
      threshold, other models were around 70 % sensitive. However, these models were
      not considered clinically useful regarding their positive predictive values (PPV)
      especially in BMDs <=02.5. With regard to different measures of diagnostic
      property, none of these models were good screening tools for osteoporosis or
      fracture threshold. Although some of them are sensitive, considering other
      measures such as PPV indicates that they are not completely useful for clinical
      use. Attempts should be made for developing newer prescreening methods and
      calibration of the existing models with regard to the studied population. 

PMID- 25980684
TI  - Cloning, tissue distribution and effects of fasting on mRNA expression levels of
      leptin and ghrelin in red-bellied piranha (Pygocentrus nattereri).
AB  - cDNAs encoding the appetite regulating peptides leptin and ghrelin were isolated
      in red-bellied piranha (Characiforme, Serrasalmidae) and their mRNA tissue and
      brain distributions examined. When compared to other fish, the sequences obtained
      for all peptides were most similar to that of other Characiforme fish and
      Siluriformes. All peptides were widely expressed within the brain and in several
      peripheral tissues, including gastrointestinal tract. In order to better
      understand the role of these peptides in the regulation of feeding of red-bellied
      piranha, the mRNA expression levels of leptin and ghrelin were examined in both
      brain and intestine, in fed and 7-day fasted fish. No significant differences in
      expression were seen in whole brain for either peptide. Within the intestine,
      there was a decrease in leptin mRNA expression and an increase in ghrelin mRNA
      expression in fasted fish, compared to fed fish. The results suggest that leptin
      and ghrelin might play a major role in the regulation of feeding and energy
      homeostasis of red-bellied piranha and this role might be more prominent in the
      intestine than in the brain. 

PMID- 25980685
TI  - Increased inflammation and decreased insulin sensitivity indicate metabolic
      disturbances in zoo-managed compared to free-ranging black rhinoceros (Diceros
      bicornis).
AB  - Black rhinoceros (rhinos) living in zoos express a host of unusual disease
      syndromes that are associated with increased morbidity and mortality, including
      hemolytic anemia, rhabdomyolysis, hepatopathy and ulcerative skin disease,
      hypophosphatemia and iron overload. We hypothesized that iron overload is a
      consequence and indicator of disturbances related to inflammation and
      insulin/glucose metabolism. The objectives of this study were to: (1) generate
      the first baseline information on biomarkers of inflammation (tumor necrosis
      factor alpha [TNFalpha], serum amyloid A [SAA]), insulin sensitivity (insulin,
      glucose and proxy calculations of insulin sensitivity), phosphate and iron stores
      (ferritin) using banked serum from free-ranging black rhinos; and (2) then
      compare serum biomarkers between zoo-managed (n=86 individuals) and free-ranging
      (n=120) animals. Enzyme immunoassays were validated for serum and then biomarker
      levels analyzed using mixed models while controlling for sex, age and year of
      sample collection. Concentrations of TNFalpha, SAA, insulin and insulin-to
      glucose ratio were higher (P<0.05) in black rhinos managed in ex situ conditions
      compared to free-living counterparts. Findings indicate that the captive
      environment is contributing to increased inflammation and decreased insulin
      sensitivity in this endangered species. 

PMID- 25980686
TI  - The changing face of the paediatric microlaryngobronchoscopy (MLB): A two year
      prospective study.
AB  - BACKGROUND: Changes in the management and survival of paediatric patients with
      airway complaints combined with improving survival rates of premature babies have
      resulted in a different patient population for the paediatric airway surgeon than
      that previously described in the literature. OBJECTIVES: To examine the
      presentation, diagnosis, clinical course and outcomes for patients undergoing
      microlaryngobronchoscopy (MLB). STUDY DESIGN: 2 year prospective longitudinal
      study. STUDY POPULATION: 210 microlaryngobronchoscopy examinations were performed
      on a total of 102 patients. Mean age at initial examination was 29.4 months with
      a male preponderance (68%). RESULTS: 72 (71%) patients had other documented
      medical co-morbidities with 30 children having no previous medical history. Of
      the 102 patients the primary diagnoses were: Subglottic Stenosis (29.4%),
      Laryngomalacia (20.6%), Laryngeal Cleft (16.7%), Normal Anatomy (11.8%) and Vocal
      Cord pathology (5.9%). The average rate of diagnoses per patient for the whole
      cohort was 1.57. Of those patients with a diagnosis on examination, 40 had a
      solitary diagnosis whilst 50 patients (55.5%) were found to have multiple
      diagnoses, equating to 2.35 diagnoses per patient. Children with a history of
      prematurity accounted for 18.6% of our cohort with a 100% rate of laryngo
      tracheal pathology on examination and an average number of diagnoses per child of
      2.21. CONCLUSION: Our cohort illustrates the varied population served by today's
      paediatric airway surgeon alongside common diagnoses and co-pathologies affecting
      our patients.

PMID- 25980687
TI  - Powered intracapsular tonsillotomy vs. conventional extracapsular tonsillectomy
      for pediatric OSA: A retrospective study about efficacy, complications and
      quality of life.
AB  - OBJECTIVES: To compare the results of powered intracapsular tonsillectomy and
      adenoidectomy (PITA) with that of conventional extracapsular tonsillectomy and
      adenoidectomy (ECTA) in treatment of pediatric obstructive sleep apnea (OSA) as
      regard efficacy, complications including postoperative pain and bleeding, and
      quality of life. METHODS: Four hundred fifty children with adenotonsillar
      hyperplasia (with age range from 3 to 14 years) underwent tonsillectomy +/-
      adenoidectomy (251 PITA and 199 ECTA) from January 2012 till October 2014 for
      OSA. Outcome measures included Obstructive Sleep Apnea Survey (OSA-18), the
      number of cases treated for post tonsillectomy bleeding with particular regard to
      the number of cases that needed readmission, the need for analgesics, the visual
      analog scale (VAS) for post-operative pain, the perceived satisfaction assessed
      by post tonsillectomy quality of life questionnaire (QOL). RESULTS: OSA-18 scores
      proved that both PITA and ECTA were equally effective in curing upper airway
      obstructive symptoms as reflected by the targeted questionnaire. Postoperative
      bleeding was significantly lower in the PITA group (P<0.01). Postoperative pain
      and number of needed analgesic doses were significantly lower in the PITA group
      (P=0.01, P<0.01, respectively). Satisfaction and quality of life were
      significantly higher in the PITA group (P<0.01). CONCLUSION: PITA is proved to be
      effective in treating pediatric OSA with less morbidity, less complications in
      terms of postoperative bleeding mainly with better satisfaction and lower
      incidence of regrowth.

PMID- 25980688
TI  - Fusobacterial head and neck infections in children.
AB  - Fusobacterium species are increasingly recognized as a cause of head and neck
      infections in children. These infections include acute and chronic otitis,
      sinusitis, mastoiditis, and tonsillitis; peritonsillar and retropharyngeal
      abscesses; Lemierre syndrome; post-anginal cervical lymphadenitis; and
      periodontitis. They can also be involved in brain abscess and bacteremia
      associated with head and neck infections. This review describes the clinical
      spectrum of head and neck fusobacterial infection in children and their
      management. 

PMID- 25980690
TI  - Monitoring and evaluation of patient involvement in clinical practice guideline
      development: lessons from the Multidisciplinary Guideline for Employment and
      Severe Mental Illness, the Netherlands.
AB  - OBJECTIVE: The aim of this study was to gain better insight into the quality of
      patient participation in the development of clinical practice guidelines and to
      contribute to approaches for the monitoring and evaluation of such initiatives.
      In addition, we explore the potential of a dialogue-based approach for
      reconciliation of preferences of patients and professionals in the guideline
      development processes. METHODS: The development of the Multidisciplinary
      Guideline for Employment and Severe Mental Illness in the Netherlands served as a
      case study. Methods for patient involvement in guideline development included the
      following: four patient representatives in the development group and advisory
      committee, two focus group discussions with patients, a dialogue session and
      eight case studies. To evaluate the quality of patient involvement, we developed
      a monitoring and evaluation framework including both process and outcome
      criteria. Data collection included observations, document analysis and semi
      structured interviews (n = 26). RESULTS: The quality of patient involvement was
      enhanced using different methods, reflection of patient input in the guideline
      text, a supportive attitude among professionals and attention to patient
      involvement throughout the process. The quality was lower with respect to
      representing the diversity of the target group, articulation of the patient
      perspective in the GDG, and clarity and transparency concerning methods of
      involvement. CONCLUSIONS: The monitoring and evaluation framework was useful in
      providing detailed insights into patient involvement in guideline development.
      Patient involvement was evaluated as being of good quality. The dialogue-based
      approach appears to be a promising method for obtaining integrated stakeholder
      input in a multidisciplinary setting.

PMID- 25980691
TI  - The plausibility of visual information for hand ownership modulates multisensory
      synchrony perception.
AB  - We are frequently changing the position of our bodies and body parts within
      complex environments. How does the brain keep track of one's own body? Current
      models of body ownership state that visual body ownership cues such as viewed
      object form and orientation are combined with multisensory information to
      correctly identify one's own body, estimate its current location and evoke an
      experience of body ownership. Within this framework, it may be possible that the
      brain relies on a separate perceptual analysis of body ownership cues (e.g. form,
      orientation, multisensory synchrony). Alternatively, these cues may interact in
      earlier stages of perceptual processing-visually derived body form and
      orientation cues may, for example, directly modulate temporal synchrony
      perception. The aim of the present study was to distinguish between these two
      alternatives. We employed a virtual hand set-up and psychophysical methods. In a
      two-interval force-choice task, participants were asked to detect temporal delays
      between executed index finger movements and observed movements. We found that
      body-specifying cues interact in perceptual processing. Specifically, we show
      that plausible visual information (both form and orientation) for one's own body
      led to significantly better detection performance for small multisensory
      asynchronies compared to implausible visual information. We suggest that this
      perceptual modulation when visual information plausible for one's own body is
      present is a consequence of body-specific sensory predictions. 

PMID- 25980693
TI  - Determination of thiocyanate in saliva by headspace gas chromatography-mass
      spectrometry, following a single-step aqueous derivatization with triethyloxonium
      tetrafluoroborate.
AB  - A novel method for the determination of salivary thiocyanate is presented.
      Thiocyanate was converted into ethyl thiocyanate by single-step aqueous
      derivatization based on triethyloxonium tetrafluoroborate and measured by gas
      chromatography-mass spectrometry (15 min runtime). The ethyl thiocyanate
      derivative is volatile and can be sampled from the headspace. The derivatization
      chemistry proposed allows for separation of the analyte from saliva matrix whose
      introduction in the measurement system is avoided. Quantitation of the analyte
      was obtained by isotope dilution, employing a (13)C-enriched thiocyanate as
      internal standard. Technical details and fundamental aspects of derivatization
      chemistry and calibration strategy are presented. The method was validated by
      comparison with a standard method based on ion chromatography. The two
      independent methodologies produced results in agreement within 3%. Also a three
      level spike recovery test was carried out for validation purpose and quantitative
      recoveries were attained. The method is fast, simple, safe, and sensitive.
      Measurement of a 1 mL volume 50 ng/g of thiocyanate standard produced a signal-to
      noise ratio of 250 for the analytical peak. This method is therefore suitable for
      ultra-trace determination of thiocyanate (low part-per-billion range). For the
      application described the full detection potential of the method was not required
      and the sample preparation presented has been designed for quantitation of saliva
      samples containing 1-400 MUg/g of thiocyanate with a combined standard
      uncertainty of 2% relative for saliva samples containing 25 MUg/g of thiocyanate.
      This method was applied for the determination of thiocyanate in human saliva
      samples.

PMID- 25980689
TI  - Splicing: is there an alternative contribution to Parkinson's disease?
AB  - Alternative splicing is a crucial mechanism of gene expression regulation that
      enormously increases the coding potential of our genome and represents an
      intermediate step between messenger RNA (mRNA) transcription and protein
      posttranslational modifications. Alternative splicing occupies a central position
      in the development and functions of the nervous system. Therefore, its
      deregulation frequently leads to several neurological human disorders. In the
      present review, we provide an updated overview on the impact of alternative
      splicing in Parkinson's disease (PD), the second most common neurodegenerative
      disorder worldwide. We will describe the alternative splicing of major PD-linked
      genes by collecting the current evidences about this intricate and not carefully
      explored aspect. Assessing the role of this mechanism on PD pathobiology may
      represent a central step toward an improved understanding of this complex
      disease. 

PMID- 25980692
TI  - A novel 9 * 9 map-based solvent selection strategy for targeted counter-current
      chromatography isolation of natural products.
AB  - Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography
      technique for separation and purification of complex mixtures like natural
      products extracts and synthetic chemicals. However, CCC is still a challenging
      process requiring some special technical knowledge especially in the selection of
      appropriated solvent systems. In this work, we introduced a new 9 * 9 map-based
      solvent selection strategy for CCC isolation of targets, which permit more than
      60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start
      candidates for the selection of solvent systems. Among these solvent systems,
      there are clear linear correlations between partition coefficient (K) and the
      system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K =
      1) may be hit by measurement of k values of the target only in two random solvent
      systems. Besides this, surprisingly, we found that through two sweet spots, we
      could get a line ("Sweet line") where there are infinite sweet solvent systems
      being suitable for CCC separation. In these sweet solvent systems, the target has
      the same partition coefficient (K) but different solubilities. Thus, the better
      sweet solvent system with higher sample solubility can be obtained for high
      capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet
      zone") where all solvent systems have their own sweet partition coefficients
      values for the target in range of 0.4 < K< 2.5 or extended range of 0.25 < K <
      16. All results were validated by using 14 pure GUESSmix mimic natural products
      as standards and further confirmed by isolation of several targets including
      honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and
      tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to
      get a suitable solvent system only by making a simple screening two to four
      HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without
      special knowledge or comprehensive standards as references. This is an important
      advancement for solvent system selection and also will be very useful for
      isolation of current natural products including Traditional Chinese Medicines.

PMID- 25980694
TI  - Metabolomic analysis of swine urine treated with beta2-agonists by ultra-high
      performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
AB  - The illegal use of beta2-agonists in livestock production was previously detected
      by efficient methods based on mass spectrometry to control the residues of these
      drugs. Nevertheless, such methods still remain a challenging task for authorities
      who monitor these residues because the use of "cocktails" composed of mixtures of
      low amounts of several substances as well as the synthesis of new compounds of
      unknown structure prevent efficient prevention of illegal use of growth-promoting
      agents. Here, we outlined a metabolomics-based strategy for detecting the use of
      "cocktails" composed of mixtures of low amounts of three beta2-agonists via urine
      profiling. Urine profiles of controls and swine treated with mixture of low
      amounts of three substances (clenbuterol, salbutamol, and ractopamine) were
      analyzed with ultra-high performance liquid chromatography coupled with
      quadrupole time-of-flight mass spectrometry. The metabolic differences between
      controls and beta2-agonists-treated groups were compared using multivariate data
      analysis. Fourteen metabolites were identified related with the beta2-agonists
      treatment, while two co-biomarkers, 2-indolecarboxylic acid and fluorometholone
      acetate, either in single or "cocktails" of low-dose mixture of clenbuterol,
      salbutamol, and ractopamine, could be considered as diagnostic markers for the
      detection of illegal use of beta2-agonists. The results of depletion study
      demonstrated that it is practical to use the markers for monitoring of beta2
      agonists. 

PMID- 25980695
TI  - One-pot preparation of a sulfamethoxazole functionalized affinity monolithic
      column for selective isolation and purification of trypsin.
AB  - A facile and efficient "one-pot" copolymerization strategy was used for the
      preparation of sulfonamide drug (SA) functionalized monolithic columns. Two novel
      SA-immobilized methacrylate monolithic columns, i.e. poly(GMA-SMX-co-EDMA) and
      poly(GMA-SAA-co-EDMA) were prepared by one-pot in situ copolymerization of the
      drug ligand (sulfamethoxazole (SMX) or sulfanilamide (SAA)), the monomer
      (glycidyl methacrylate, GMA) and the cross-linker (ethylene dimethacrylate, EDMA)
      within 100 MUm i.d. capillaries under optimized polymerization conditions. The
      physicochemical properties and column performance of the fabricated monolithic
      columns were characterized by elemental analysis, scanning electron microscopy
      and micro-HPLC. Satisfactory column permeability, efficiency and separation
      performance were obtained on the optimized poly(GMA-SMX-co-EDMA) monolithic
      column for small molecules, such as a standard test mixture and eight aromatic
      ketones. Notably, it was found that the poly(GMA-SMX-co-EDMA) monolith showed a
      selective affinity to trypsin, while the poly(GMA-SAA-co-EDMA) monolith
      containing sulfanilamide did not exhibit such affinity at all. This research not
      only provides a novel monolith for the selective isolation and purification of
      trypsin, but it also offers the possibility to easily prepare novel drug
      functionalized methacrylate monoliths through a one-pot copolymerization
      strategy.

PMID- 25980696
TI  - Low expression of B-cell-associated protein 31 in human primary hepatocellular
      carcinoma correlates with poor prognosis.
AB  - AIMS: The aim of the present study was to investigate the prognostic value of B
      cell associated protein 31 (BAP31) in human primary hepatocellular carcinoma
      (HCC). METHODS AND RESULTS: BAP31 levels were evaluated by immunohistochemistry
      on tissue microarrays. The integral optical density, representing the expression
      level of BAP31 in each tissue sample, was calculated with image-pro plus.
      Immunohistochemical analysis of BAP31 levels in 74 paired HCC tissues and
      peritumoral non-cancerous tissues showed that BAP31 expression was significantly
      higher in HCC tumour tissues (P = 0.025). The prognostic value of BAP31 in HCC
      was evaluated in 234 cases in a training cohort and in 63 cases in a validation
      cohort. The expression level of BAP31 was significantly correlated with overall
      survival (OS) in both the training cohort and the validation cohort. The lower
      the level of BAP31 expression in HCC tissue, the poorer the prognosis. Univariate
      and multivariate analyses showed that the expression level of BAP31 in HCC was an
      independent prognostic factor for OS in both the training cohort and the
      validation cohort. CONCLUSIONS: BAP31 expression is an independent prognostic
      factor for OS of patients with postoperative HCC, and low expression levels of
      BAP31 in HCC may indicate poor outcomes of HCC patient after surgical resection.

PMID- 25980697
TI  - Letter to the Editor.

PMID- 25980699
TI  - The experiences of patients undertaking a 'virtual' cardiac rehabilitation
      program.
AB  - Cardiac rehabilitation programs (CRP) are medically supervised, multidisciplinary
      programs that provide secondary prevention aimed at addressing risk factors and
      improving lifestyle behaviours for patients following an acute cardiac event.
      CRPs have been demonstrated to be a cost-effective and evidence-based mechanism
      to improve patient outcomes, but despite the known benefits of these programs,
      uptake remains poor. Poor attendance has been linked to many factors, but
      geographical accessibility is a key concern, since many CRPs are limited to
      hospitals in urban areas. The widespread availability of the Internet has made it
      possible to provide virtual health services to populations that may have
      previously been hard to access. This paper examines the qualitative findings from
      a 16-month mixed methods randomized controlled trial examining the impact of a
      virtual CRP (vCRP). The vCRP was revealed to be an accessible, appropriate,
      convenient and effective way to deliver cardiac rehabilitation services, with
      patients experiencing both clinical improvements and a high level of
      satisfaction. To understand the experience of patients undertaking the vCRP, semi
      structured interviews were undertaken with a purposive sample of 22 participants.
      An analysis of the qualitative interviews revealed that the vCRP improved
      participants' access to healthcare professionals, supported them to make healthy
      choices, and enhanced feelings of accountability due to greater surveillance.
      Barriers to participation, such as computer literacy, and general perceptions of
      a vCRP were also examined. Further investigation into the use and long-term
      effectiveness of virtual programs across a broader range of healthcare settings
      is warranted, particularly in those with multiple chronic diseases and those
      located in rural and remote communities. 

PMID- 25980698
TI  - Bridging the Distance in the Caribbean: Telemedicine as a means to build capacity
      for care in paediatric cancer and blood disorders.
AB  - Over the past 50 years, survival for children in high-income countries has
      increased from 30% to over 80%, compared to 10-30% in low and middle income
      countries (LMIC). Given this gap in survival, established paediatric cancer
      treatment centres, such as The Hospital for Sick Children (SickKids) are well
      positioned to share clinical expertise. Through the SickKids Centre for Global
      Child Health, the SickKids-Caribbean Initiative (SCI) was launched in March 2013
      to improve the outcomes and quality of life for children with cancer and blood
      disorders in the Caribbean. The six participating Caribbean countries are among
      those defined by the United Nations as Small Island Developing States, due to
      their small size, remote location and limited accessibility. Telemedicine
      presents an opportunity to increase their accessibility to health care services
      and has been used by SCI to facilitate two series of interprofessional rounds.
      Case Consultation Review Rounds are a forum for learning about diagnostic work
      up, management challenges and treatment recommendations for these diseases. To
      date, 54 cases have been reviewed by SickKids staff, of which 35 have been
      presented in monthly rounds. Patient Care Education Rounds provide nurses and
      other staff with the knowledge base needed to safely care for children and
      adolescents receiving treatment. Five of these rounds have taken place to date,
      with over 200 attendees. Utilized by SCI for both clinical and non-clinical
      meetings, telemedicine has enhanced opportunities for collaboration within the
      Caribbean region. By building capacity and nurturing expert knowledge through
      education, SCI hopes to contribute to closing the gap in childhood survival
      between high and low-resource settings. 

PMID- 25980701
TI  - Scaling up the use of remote patient monitoring in Canada.
AB  - Evidence supporting the use of remote patient monitoring (RPM) as a cost
      effective means of keeping patients from being re-admitted to hospitals or making
      repeated emergency department visits is growing, especially for the treatment of
      chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF).
      A recent study funded by Canada Health Infoway, titled Connecting Patients with
      Providers: A Pan-Canadian Study on Remote Patient Monitoring, aimed to assess the
      current state of RPM solutions; to examine the evidence for patient and health
      system benefits achieved both in Canada and internationally; and to determine the
      critical success factors needed to support further investment and scaling-up of
      RPM solutions across the Canadian health care system. Break-even analysis of four
      different implementations reviewed in this study demonstrated that RPM programs
      can be viable and sustainable for large and small jurisdictions; however, more
      evidence is needed with regards to a number of potential applications for RPM
      beyond the management of COPD and CHF. 

PMID- 25980700
TI  - ECHO Ontario Chronic Pain & Opioid Stewardship: Providing Access and Building
      Capacity for Primary Care Providers in Underserviced, Rural, and Remote
      Communities.
AB  - Chronic pain is a prevalent and serious problem in the province of Ontario.
      Frontline primary care providers (PCPs) manage the majority of chronic pain
      patients, yet receive minimal training in chronic pain. ECHO (Extension for
      Community Healthcare Outcomes) Ontario Chronic Pain & Opioid Stewardship aims to
      address the problem of chronic pain management in Ontario. This paper describes
      the development, operation, and evaluation of the ECHO Ontario Chronic Pain
      project. We discuss how ECHO increases PCP access and capacity to manage chronic
      pain, the development of a community of practice, as well as the limitations of
      our approach. The ECHO model is a promising approach for healthcare system
      improvement. ECHO's strength lies in its simplicity, adaptability, and use of
      existing telemedicine infrastructure to increase both access and capacity of PCPs
      in underserviced, rural, and remote communities. 

PMID- 25980702
TI  - Building a patient-centered hospital web site: best practices in china.
AB  - In this case study, based on six criteria, four Chinese hospitals were chosen
      from a national sample to showcase, through content analysis and in-depth
      interviews, the best practices of serving patients online. The extensive findings
      have addressed the following three questions: what these hospitals have in common
      in their Web development, what problems and challenges they are facing, and how
      they have excelled in serving their patients online. The study concludes that,
      like larger hospitals, smaller hospitals can also excel in creating an
      outstanding Web site to serve their patients so long as they truly care about
      their patients, have a clear vision and strong expertise in IT development. The
      study also concludes that Chinese private hospitals can learn from these state
      owned hospitals in establishing a good reputation through professional and
      responsible interaction with patients. The four hospitals studied may shed light
      on the Web development in many other Chinese hospitals that are going through the
      same healthcare new media adoption. The findings from this study can also help
      Chinese hospitals form their visions in serving patients online. 

PMID- 25980703
TI  - Perspectives of Champlain BASE Specialist Physicians: Their Motivation,
      Experiences and Recommendations for Providing eConsultations to Primary Care
      Providers.
AB  - Electronic consultation can improve access to specialist care. However,
      specialists have been identified as less likely to adopt electronic solutions in
      clinical settings. We conducted an online survey to explore the perspectives of
      specialists who use the Champlain BASE eConsult service in Eastern Ontario,
      Canada. Specialists were asked their opinions on experience with the service,
      their current consult/referral practices, recommendations for change and
      expansion of the service, and compensation models. We tabulated descriptive
      statistics from the multiple choice and Likert scale responses and performed a
      content analysis with an emergent code strategy for open-text responses.
      Specialists (n=34, 77% response rate) agreed that the Champlain BASE eConsult
      service is a feasible way to improve access to specialist care (94%), improves
      communication between specialists and primary care providers (PCPs) (94%), has
      educational value for PCPs (91%), and is user friendly (82%). A majority of
      specialists (88%) felt the service should be expanded provincially and 67% felt
      it should allow specialist-to-specialist consultation. 88% of specialists agreed
      that the current compensation process is best. This study provides an in-depth
      look at the perspective of the specialist physicians who use the Champlain BASE
      eConsult service. Specialists stated specific recommendations for change that
      will allow us to ensure the service remains sustainable. 

PMID- 25980704
TI  - Improving Mental Health Care for Young Adults in Badakshan Province of
      Afghanistan Using eHealth.
AB  - Decades of war, social problems and poverty, have led large number of Afghan
      youth aged between 18-25 years suffering from mental health problems. Other
      important contributing factors include extreme poverty, insecurity, and violence
      and gender disparities, contributing to worsening mental and emotional health
      conditions in the country. The reported project is designed to strengthen the
      health system for improving mental health services in the province of Badakshan
      by improving awareness in the community and empowering frontline health workers.
      The project uses technological innovations, in combination with traditional
      approaches, to reduce stigma, enhance capacity of health providers and improve
      access to the specialist. The project also focuses on skills development of
      health providers, and empowering them to provide quality mental health services
      through access to interactive protocols, Management Information system and
      telemedicine. 

PMID- 25980705
TI  - Improving Access to Pediatric Cardiology in Cape Verde via a Collaborative
      International Telemedicine Service.
AB  - This paper addresses the role of international telemedicine services in
      supporting the evacuation procedures from Cape Verde to Portugal, enabling better
      quality and cost reductions in the management of the global health system. The
      Cape Verde, as other African countries, health system lacks many medical
      specialists, like pediatric cardiologists, neurosurgery, etc. In this study, tele
      cardiology shows good results as diagnostic support to the evacuation decision.
      Telemedicine services show benefits while monitoring patients in post-evacuation,
      helping to address the lack of responsive care in some specialties whose actual
      use will help save resources both in provision and in management of the
      evacuation procedures. Additionally, with tele-cardiology collaborative service
      many evacuations can be avoided whereas many cases will be treated and followed
      locally in Cape Verde with remote technical support from Portugal. This
      international telemedicine service enabled more efficient evacuations, by
      reducing expenses in travel and housing, and therefore contributed to the health
      system's improvement. This study provides some evidence of how important
      telemedicine really is to cope with both the geography and the shortage of
      physicians. 

PMID- 25980706
TI  - Improving access to cardiac rehabilitation using the internet: a randomized
      trial.
AB  - Cardiac rehabilitation (CR) is essential for secondary prevention, yet only 10%
      30% of eligible patients attend as geographical proximity is a major barrier. We
      evaluated a 'virtual' CR program (vCRP) delivered by the Internet to patients in
      small urban and rural areas. In our study, in-patients (n=78) with acute coronary
      syndrome or post-revascularization were randomized to usual care (UC) or vCRP.
      The vCRP was a four-month program that included heart rate monitoring;
      physiologic data capture; education sessions; ask-an-expert sessions; and chat
      sessions with a nurse, exercise specialist and dietitian. Participants were
      assessed at baseline and four months, and followed for another 12 months. The
      primary outcome was change in maximal time on the treadmill stress test (MTT)
      between groups adjusted for age, sex, diabetes status and Internet use for health
      information. The vCRP resulted in a greater increase in MTT by 45.7 seconds (95%
      CI: 1.0, 90.5) compared to usual care (p=0.045). Cholesterol levels and dietary
      quality improved in the vCRP compared to the UC group. Participants perceived the
      vCRP to be an accessible, convenient and effective way to received healthcare.
      Eleven (30%) and 6 (18%) participants in the UC and vCRP groups, respectively,
      had cardiovascular-related events (p=0.275). In conclusion, the vCRP was safe and
      effective and resulted in sustainable risk reduction without the requirement of
      face-to-face visits and directly monitored exercise. 

PMID- 25980707
TI  - What are the Costs of Improving Access to Specialists through eConsultation? The
      Champlain BASE Experience.
AB  - Excessive wait times and poor access to care are among the most significant
      problems facing health care service delivery in Canada and beyond. We implemented
      the Champlain BASE eConsult service in the region of Ottawa, Canada to increase
      access to specialist care. We have collected ongoing utilization data and
      provider surveys over a three year period, providing a unique opportunity to
      explore the economic aspects of this multispecialty eConsult service. This is an
      economic evaluation from the perspective of the payer: the Ministry of Health and
      Long-Term Care of Ontario. All eConsults submitted during April 1, 2011 to March
      31, 2014 were included. We attributed cost savings only to those cases where an
      eConsult led to the avoidance of a face-to-face specialist visit. A total of 2606
      eConsults directed to 27 different speciality groups were included. In 40.3%
      (n=1051) of cases processed, a face-to-face specialist visit was originally
      planned but avoided as a result of eConsult, while 29% led to a referral. The
      estimated cost per eConsult for Years 1, 2, and 3 were $131.05, $10.34, and $6.45
      respectively. Results from a sensitivity analysis project that the eConsult
      service will break even once we reach 7818 eConsults. This is one of the first
      studies to examine costs across a multispecialty eConsult service. We saw a
      marked decrease in the cost per eConsult over each annual period. Future research
      is needed to identify and examine similar outcomes that may lead to cost savings.

PMID- 25980708
TI  - The current state of electronic consultation and electronic referral systems in
      Canada: an environmental scan.
AB  - Access to specialist care is a point of concern for patients, primary care
      providers, and specialists in Canada. Innovative e-health platforms such as
      electronic consultation (eConsultation) and referral (eReferral) can improve
      access to specialist care. These systems allow physicians to communicate
      asynchronously and could reduce the number of unnecessary referrals that clog
      wait lists, provide a record of the patient's journey through the referral
      system, and lead to more efficient visits. Little is known about the current
      state of eConsultation and eReferral in Canada. The purpose of this work was to
      identify current systems and gain insight into the design and implementation
      process of existing systems. An environmental scan approach was used, consisting
      of a systematic and grey literature review, and targeted semi-structured key
      informant interviews. Only three eConsultation/eReferral systems are currently in
      operation in Canada. Four themes emerged from the interviews: eReferral is an end
      goal for those provinces without an active eReferral system, re-organization of
      the referral process is a necessity prior to automation, engaging the end-user is
      essential, and technological incompatibilities are major impediments to progress.
      Despite the acknowledged need to improve the referral system and increase
      government spending on health information technology, eConsultation and eReferral
      systems remain scarce as Canada lags behind the rest of the developed world. 

PMID- 25980709
TI  - Achieving greater consistency in telehealth project evaluations to improve
      organisational learning.
AB  - Telehealth pilot projects and trial implementations are numerous but are often
      not fully evaluated, preventing construction of a sound evidence base and so
      limiting their adoption. We describe the need for a generic Telehealth project
      evaluation framework, within which evaluation is undertaken based on existing
      health systems performance indicators, using appropriately chosen measures. We
      provide two case studies explaining how this approach could be applied, in
      Australian and Canadian settings. It is argued that this framework type of
      approach to evaluation offers better potential for incorporating the learnings
      from resultant evaluations into business decisions by "learning organisations",
      through alignment with organisational performance considerations. 

PMID- 25980710
TI  - Governance and management of national telehealth programs in Asia.
AB  - Telehealth and telemedicine are increasingly becoming accepted practices in Asia,
      but challenges remain in deploying these services to the farthest areas of many
      developing countries. With the increasing popularity of universal health
      coverage, there is a resurgence in promoting telehealth services. But while
      telehealth that reaches the remotest part of a nation is the ideal endpoint, such
      goals are burdened by various constraints ranging from governance to funding to
      infrastructure and operational efficiency. OBJECTIVES: enumerate the public
      funded national telehealth programs in Asia and determine the state of their
      governance and management. METHOD: Review of literature, review of official
      program websites and request for information from key informants. CONCLUSIONS:
      While there are national telehealth programs already in operation in Asia, most
      experience challenges with governance and subsequently, with management and
      sustainability of operations. It is important to learn from successful programs
      that have built and maintained their services over time. An IT governance
      framework may assist countries to achieve success in offering telehealth and
      telemedicine to their citizens.

PMID- 25980711
TI  - Telehomecare Reduces ER Use and Hospitalizations at William Osler Health System.
AB  - The Ontario Telemedicine Network's Telehomecare initiative brings together
      specially trained clinicians and technology to coach patients with COPD and/or
      heart failure to monitor vital signs and manage their health at home. The
      objective of the study was to evaluate pre- and post-enrollment and post
      discharge data captured by Telehomecare host William Osler Health System (WOHS).
      Results demonstrate a 46% reduction in emergency department use and a 53%
      reduction in hospitalizations post-enrollment compared to pre-enrollment. Average
      length of stay (LOS) dropped by 25% of a day compared to pre-enrollment. In
      addition, six months after Telehomecare discharge, inpatient admissions and
      emergency department visits continued to decline, by 65% and 57% respectively,
      compared to pre-enrollment. While average LOS increased between pre-enrollment
      and post-discharge, the reduction in acute inpatient episodes created a net
      reduction in accumulated inpatient days of 563.16 days (63% reduction). The WOHS
      Telehomecare results strongly support the positive influence of the program on
      health system utilization and the development of effective long-term self
      management skills. Next steps could include reviewing, more closely, the reasons
      for hospital utilization and undertaking a cost-benefit analysis to support
      further expansion of the program to address other chronic illness and care needs.

PMID- 25980712
TI  - Telehealth application in occupational health.
AB  - While occupational health is a significant driver of population health,
      productivity, and well-being in Canadian society, most workers do not currently
      have adequate access to qualified occupational health services. A case study is
      used to demonstrate the utility of a telehealth approach to service delivery. 

PMID- 25980713
TI  - Exploring the views of emergency department staff on the use of videoconferencing
      for mental health emergencies in southwestern Ontario.
AB  - Patients presenting to a rural emergency department (ED) with mental health
      symptoms have difficulty accessing services of mental health professionals [1,2].
      Videoconferencing (VC) has been found to improve patient access to health
      services that require specialist care in rural EDs [3,4,5]. Although previous
      studies highlight the benefit of using VC for patients presenting with mental
      health emergencies, no study has investigated the current views and use of VC for
      mental health emergencies in EDs in Southwestern Ontario [3,5,6]. To explore the
      views of ED staff regarding the use of VC in mental health emergencies,
      structured telephone interviews were conducted with representatives from EDs in
      the Erie St. Clair and Southwest Local Health Integration Networks (LHIN).
      Participants noted that using VC for mental health emergencies may improve
      patient experience and benefit crisis response teams. VC was perceived by some
      participants as a means to expedite the direct assessment of a patient presenting
      with a mental health emergency by a mental health specialist. However several
      participants stated that using VC for mental health emergencies strains ED
      resources. Lack of use and difficulty accessing a psychiatrist were identified as
      potential barriers to implementing the use of VC for mental health emergencies. 

PMID- 25980714
TI  - Hype, harmony and human factors: applying user-centered design to achieve
      sustainable telehealth program adoption and growth.
AB  - Despite decades of international experience with the use of information and
      communication technologies in healthcare delivery, widespread telehealth adoption
      remains limited and progress slow. Escalating health system challenges related to
      access, cost and quality currently coincide with rapid advancement of affordable
      and reliable internet based communication technologies creating unprecedented
      opportunities and incentives for telehealth. In this paper, we will describe how
      Human Factors Engineering (HFE) and user-centric elements have been incorporated
      into the establishment of telehealth within a large academic medical center to
      increase acceptance and sustainability. Through examples and lessons learned we
      wish to increase awareness of HFE and its importance in the successful
      implementation, innovation and growth of telehealth programs. 

PMID- 25980715
TI  - eHealth for Remote Regions: Findings from Central Asia Health Systems
      Strengthening Project.
AB  - Isolated communities in remote regions of Afghanistan, Kyrgyz Republic, Pakistan
      and Tajikistan lack access to high-quality, low-cost health care services,
      forcing them to travel to distant parts of the country, bearing an unnecessary
      financial burden. The eHealth Programme under Central Asia Health Systems
      Strengthening (CAHSS) Project, a joint initiative between the Aga Khan
      Foundation, Canada and the Government of Canada, was initiated in 2013 with the
      aim to utilize Information and Communication Technologies to link health care
      institutions and providers with rural communities to provide comprehensive and
      coordinated care, helping minimize the barriers of distance and time. Under the
      CAHSS Project, access to low-cost, quality health care is provided through a
      regional hub and spoke teleconsultation network of government and non-government
      health facilities. In addition, capacity building initiatives are offered to
      health professionals. By 2017, the network is expected to connect seven Tier 1
      tertiary care facilities with 14 Tier 2 secondary care facilities for
      teleconsultation and eLearning. From April 2013 to September 2014, 6140
      teleconsultations have been provided across the project sites. Additionally, 52
      new eLearning sessions have been developed and 2020 staff members have benefitted
      from eLearning sessions. Ethics and patient rights are respected during project
      implementation. 

PMID- 25980716
TI  - Community Health Nursing through a Global Lens.
AB  - Community Health Nursing (N456) is a required senior clinical course in the
      undergraduate nursing curriculum at the University of Michigan in which students
      learn to assess and address the health of populations and communities. In 2012,
      we began our efforts to internationalize the curriculum using a globally engaged
      nursing education framework. Our goal is for all students to have an
      intercultural learning experience understanding that all students are unable to
      travel internationally. Therefore, this intercultural learning was implemented
      through a range of experiences including actual immersion, virtual activities
      (videoconferencing) and interventions with local vulnerable populations. Grants
      were obtained to provide immersion experiences in Quito, Ecuador and New Delhi,
      India. Several technologies were initiated with partner nursing schools in
      Leogane, Haiti and New Delhi, India. Weekly videoconferencing utilizing BlueJeans
      software and exchange of knowledge through the Knowledge Gateway facilitated
      intercultural exchange of knowledge and culture. Local clinical groups work with
      a variety of vulnerable populations. A private blog was developed for all
      sections to share community assessment data from local and international
      communities. Qualitative evaluation data was collected for local and
      international students to begin to assess cultural competence and student
      learning. Analysis of data documented increased awareness of culture and
      identified the many positive benefits of interaction with a global partner. 

PMID- 25980717
TI  - Improved Immediate and Continued-Care Outcomes for Stroke through Community-Wide
      Data.
AB  - Strokes account for 1 of every 18 deaths in North America, and remain a major
      burden cost-wise and clinically for societies globally. Quicker and more
      clinically astute care for stroke leads to improved outcomes for the patient,
      families and the healthcare system at large. The intervention shared illustrates
      how a locally-programmable EMR with inherent community-wide communications
      capabilities leads to proven better outcomes for all. The impacts range from
      initial hospital encounter through acute-care treatment, and then more broadly
      into post-discharge care community-wide. Implications for all healthcare
      communities are established. 

PMID- 25980718
TI  - Optimal Care Mother-Baby and Outcomes through Community-wide Data Sharing,
      Interoperability and Connectivity.
AB  - The power of interoperable systems with data/information integration, central to
      achieving the goals of Telehealth, is illustrated through mutually beneficial
      sharing between Labor & Delivery (L&D) and Obstetrics (OBs) Clinics. Data shared
      between L&D and OB brought improved practice patterns and outcomes, and increased
      satisfaction at both. Staffing and skillsets were significantly improved by
      knowing complications arriving and anticipated volumes. OBs increased clinic
      efficiencies and improved patient-direct care time with improved clinical and
      cost outcomes. 

PMID- 25980719
TI  - Evaluating a Telehealth Follow-up Program for Cardiology Patients Using
      Administrative Data.
AB  - This project evaluated the effect of a telehealth follow-up intervention on
      readmission rates for patients discharged from the Saskatoon Health Region
      cardiology units with ACS or HF. 1-year readmission rates for ACS patients were
      27.4% (95% CI: [26%, 29%]) before telehealth implementation and 25.2% (95% CI:
      [24%, 27%]) after, producing an insignificant hazard ratio of 1.07 (95% CI:
      [0.97, 1.18], P=0.1899). For HF 50.3% (95% CI: [44%, 56%]) of pre-implementation
      and 47.9% (95% CI: [43%, 53%]) of post-implementation patients had a 1-year
      readmission, producing a HR of 1.04 (95% CI: [0.83, 1.26], P=0.6882). This
      analysis found no significant effect of telehealth on readmission rates for ACS
      or HF patients. 

PMID- 25980720
TI  - Analysis and Typology of Global eHealth Platforms - A Survey on Five Continents.
AB  - Driven by the diverse needs for exchanging patient, other healthcare and health
      system data with the aim to improve the overall quality and efficiency of
      healthcare provision, regions and countries globally have been developing
      electronic platforms to gather and exchange such data. Based on an initial sample
      of more than 50 potential cases, eight such platforms were analysed in detail.
      This covered issues like core public health policy goals pursued, and major
      patient and other healthcare data access and exchange characteristics driving the
      platforms surveyed. This allows for arriving at an initial, pragmatic typology of
      such platforms. It provides for a better understanding of the main objective(s)
      and the major thrust of the underlying national (or district-related) health
      policy to develop and implement such infrastructures. 

PMID- 25980721
TI  - Meeting the Semantic Challenge of the Globally Unique Identification of Medicinal
      Products - The openMedicine Approach.
AB  - To better enable cross-border healthcare delivery, particularly the exchange of
      ePrescriptions, this global undertaking advances the unique identification of
      medicinal products (MPs) and patient safety in cross-border settings. Major
      stakeholders harmonise their respective efforts to deliver * common data models
      for prescribed MPs * a common vocabulary for unambiguous definition, description,
      and identification of MPs * rules to harmonise practices of therapeutic and
      economic substitution * a global roadmap for post-project actions and
      implementations Based on earlier activities of standard development organisations
      (SDOs), use case scenarios are developed, where the identification of an MP is an
      issue, including pharmacological and pharmacokinetic attributes, clinical
      indications, and risks to be considered. Next, the univocal identification of MPs
      is addressed, for standard pre-packed ones as well as for special cases like MPs
      with multi-components, biologics, or special packaging. Impacts will be
      considerable for global healthcare services and systems as well as - through
      simplifying and speeding up the registration of new products and afterwards
      pharmacovigilance - for national and international regulatory agencies, the MPs
      industry, and, in particular, patients. 

PMID- 25980722
TI  - Re-thinking Models of Patient Empowerment.
AB  - The empowerment of citizens in relation to personal healthcare management
      includes consideration of a multi-faceted collection of elements. Simplistic
      forms of understanding which link empowerment to access provide limited
      acknowledgement of the requirement to facilitate a greater sense of health
      ownership in patients and collaborative working practices in practitioners. More
      complex attitudes to the delivery of empowered patients encompassing knowledge
      development, technological awareness and partnership approaches to healthcare
      delivery are steps in the right direction, but strain to fit currently emerging
      ideas around patient centered care. This paper posits that existing frameworks
      aimed at empowering patients for a patient centered ehealth system are
      insufficiently presented. The frameworks, which are mostly premised on an
      inequitable focus, fail to factor in the invaluableness of holism and
      technological innovation. Through a review of existing frameworks and an
      articulation of patient demands, weaknesses in current structures to support
      empowerment are explored, and key constituents of a framework for patient
      empowerment are determined. Consequently, the paper articulates a model focused
      around delivering an empowered patient in the 21(st) century healthcare system.

PMID- 25980726
TI  - Assessing changes in water flow regulation in Chongqing region, China.
AB  - Water flow regulation is an important ecosystem service that significantly
      impacts on ecological quality and social benefits. With the aim of improving our
      understanding of ecosystems and proposing strategies for optimizing ecosystem
      services, a geographic information system (GIS)-based approach was designed to
      estimate and map regulated water flow in the Chongqing region of China. In this
      study, we applied the integrated valuation of environmental services and
      tradeoffs (InVEST) model and mathematical simulations to estimate the provision
      of the regulated water flow across space and time in 2000, 2005, and 2010. The
      results indicated that this ecosystem service had improved by 2.07 % from 2000 to
      2010 as a result of human activities (such as vegetation restoration) and
      climatic interaction. Places with positive changes mainly occurred in high
      mountain areas, whereas places with negative changes were mainly distributed in
      resettlement areas along the Yangtze River. The type of ecosystem in areas with
      high mountains and steep slopes was a relatively minor contributor to the total
      service, but this ecosystem had the higher water flow regulation capacity.
      Moreover, with the increase in altitude and slope, the percentage contribution of
      forest increased significantly from 2000 to 2010; by contrast, the percentage
      contribution of cropland decreased rapidly. As for the impacts, the spatial
      variation of water flow regulation in the Chongqing region had a significant
      relation with climate and human activities at the regional scale. These results
      provided specific information that could be used to strengthen necessary public
      awareness about the protection and restoration of ecosystems.

PMID- 25980727
TI  - Metals content in otoliths of Dicentrarchus labrax from two fish farms of Sicily.
AB  - Otoliths of cultured sea bass (Dicentrarchus labrax) from two different fish
      farms of Sicily were collected and analyzed by using inductively coupled plasma
      optical emission spectroscopy. Metal content (Ba, Cd, Fe, Mg, Mn, Sr, and Zn) was
      measured in order to test the potential use of biogenic carbonates as proxies of
      dissimilar environmental conditions since the fish farms are implanted in
      opposite coastal marine areas (Gulf of Castellammare and Gulf of Gela)
      characterized by different oceanographic features and human activities. Cluster
      analysis discriminates samples as different groups on the basis of metal content.
      Results show that concentrations of Sr in the otoliths have a similar range of
      distribution and not significantly different between the two farms. Otherwise,
      Fe, Mg, Mn, and Cd show higher concentrations in otoliths collected from fish
      reared in the farm in the southern coast (Gulf of Gela), an area subject to a
      great anthropogenic pressure. Zn is the only element with higher values in the
      otoliths from the farm in the northern coast (Gulf of Trappeto) probably due to
      industrial effluent. In this work, obtained data confirm the high potential of
      trace elements measurements in these biogenic carbonates as proxies of different
      environmental conditions. 

PMID- 25980728
TI  - Trace monitoring of silver ions in food and water samples by flame atomic
      absorption spectrophotometry after preconcentration with solvent-assisted
      dispersive solid phase extraction.
AB  - In this research, a new sample treatment technique termed solvent-assisted
      dispersive solid phase extraction (SADSPE) was developed. The new method was
      based on the dispersion of the sorbent into the sample to maximize the contact
      surface. In this approach, the dispersion of the sorbent at a very low milligram
      level was achieved by injecting a mixture solution of the sorbent and disperser
      solvent into the aqueous sample. Thereby, a cloudy solution formed. The cloudy
      solution resulted from the dispersion of the fine particles of the sorbent in the
      bulk aqueous sample. After extraction, the cloudy solution was centrifuged and
      the enriched analytes in the sediment phase dissolved in ethanol and determined
      by FAAS. Under the optimized conditions, the detection limit for silver ions was
      0.8 MUg L(-1). The relative standard deviations for six separate extraction
      experiments for determination of 5 and 200 MUg L(-1) of silver ions was 3.4 and
      3.1 %. The preconcentration factor was found to be 61.7. SADSPE was successfully
      applied for trace determination of silver ions in water and food samples.

PMID- 25980729
TI  - Visibility characteristics and the impacts of air pollutants and meteorological
      conditions over Shanghai, China.
AB  - In China, visibility condition has become an important issue that concerns both
      society and the scientific community. In order to study visibility
      characteristics and its influencing factors, visibility data, air pollutants, and
      meteorological data during the year 2013 were obtained over Shanghai. The
      temporal variation of atmospheric visibility was analyzed. The mean value of
      daily visibility of Shanghai was 19.1 km. Visibility exhibited an obvious
      seasonal cycle. The maximum and minimum visibility occurred in September and
      December with the values of 27.5 and 7.7 km, respectively. The relationships
      between the visibility and air pollutant data were calculated. The visibility had
      negative correlation with NO2, CO, PM2.5, PM10, and SO2 and weak positive
      correlation with O3. Meteorological data were clustered into four groups to
      reveal the joint contribution of meteorological variables to the daily average
      visibility. Usually, under the meteorological condition of high temperature and
      wind speed, the visibility of Shanghai reached about 25 km, while visibility
      decreased to 16 km under the weather type of low wind speed and temperature and
      high relative humid. Principle component analysis was also applied to identify
      the main cause of visibility variance. The results showed that the low visibility
      over Shanghai was mainly due to the high air pollution concentrations associated
      with low wind speed, which explained the total variance of 44.99 %. These results
      provide new knowledge for better understanding the variations of visibility and
      have direct implications to supply sound policy on visibility improvement in
      Shanghai.

PMID- 25980730
TI  - Constructing Fe2O3/TiO2 core-shell photoelectrodes for efficient
      photoelectrochemical water splitting.
AB  - In this study, plasma enhanced chemical vapor deposition (PECVD) was utilized to
      co-axially modify hydrothermally grown Fe2O3 nanorod arrays by depositing a TiO2
      overlayer to create Fe2O3/TiO2 core-shell photoelectrodes. Comprehensive
      structural (XRD, SEM, TEM) and compositional (XPS) analyses were performed to
      understand the effects of the TiO2 shell on the PEC activities of the Fe2O3 core.
      It was revealed that the heterojunction structure formed between TiO2 and Fe2O3,
      significantly improved the separation efficiency of photo-induced charge carriers
      and the oxygen evolution kinetics. A maximum photocurrent density of ~900 MUA cm(
      2) at 0.6 V vs. saturated calomel electrode (SCE) was obtained for the Fe2O3/TiO2
      photoelectrodes, which was 5 and 18 times higher when compared to that of
      hydrothermally synthesized Fe2O3 and PECVD synthesized TiO2 electrodes,
      respectively. Moreover, the Fe2O3/TiO2 core-shell nanorod arrays displayed
      superior stability for PEC water splitting. During 5000 s PEC measurements, a
      steady decrease of the photocurrent was observed, mainly attributed to the
      evolution of oxygen bubbles adsorbed on the working electrodes. This observation
      was verified by the complete recovery of the PEC performance demonstrated for a
      second 5000 s PEC measurement carried out after a brief time interval (10 min)
      that allowed the electrode surface to regenerate. 

PMID- 25980731
TI  - The hen's egg chorioallantoic membrane (HET-CAM) test to predict the ophthalmic
      irritation potential of a cysteamine-containing gel: Quantification using
      Photoshop(r) and ImageJ.
AB  - A modified hen's egg chorioallantoic membrane (HET-CAM) test has been developed,
      combining ImageJ analysis with Adobe((r)) Photoshop((r)). The irritation
      potential of an ophthalmic medicine can be quantified using this method, by
      monitoring damage to blood vessels. The evaluation of cysteamine containing
      hyaluronate gel is reported. The results demonstrated that the novel gel
      formulation is non-irritant to the ocular tissues, in line with saline solution
      (negative control). In conclusion, the modification of the established HET-CAM
      test can quantify the damage to minute blood vessels. These results offer the
      possibility to formulate cysteamine in an ocular applicable gel formulation. 

PMID- 25980732
TI  - Assessment of human iron status: A cross-sectional study comparing the clinical
      utility of different laboratory biomarkers and definitions of iron deficiency in
      daily practice.
AB  - OBJECTIVES: No full international consensus exists on disease markers to be used
      for assessing the human iron status. Therefore this study was conducted to
      compare performances of serum ferritin and transferrin saturation (TSAT) versus
      soluble transferrin receptor (sTfR)/log ferritin and reticulocyte hemoglobin
      content (CHr), also known as Thomas-plot, in the diagnosis of iron deficiency
      (ID). DESIGN AND METHODS: A total of 445 consecutive hospitalized patients,
      referred for routine testing of the actual iron status, were included. Logistic
      regression models for the probability of functional ID (CHr<28pg) were
      constructed for all 445 patients, for 225 patients without (C-reactive protein
      [CRP]<=0.5mg/dL) and 220 patients with acute-phase reaction (CRP>0.5mg/dL).
      RESULTS: Based on the Thomas-plot analyses, 153/445 (34.38%) patients were
      identified with ID. When ID was diagnosed by means of serum ferritin
      levels<30ng/mL and TSAT levels<20%, 105/445 (23.60%) and 215/445 (48.31%)
      patients were identified with ID, respectively. The sTfR/log ferritin ratio
      showed the best positive predictive values (PPV) (62.50 and 64.41%) to indicate
      functional ID in patients without as well as with acute-phase reaction compared
      to sTfR (58.14 and 61.67%), ferritin (32.50 and 32.86%) and TSAT (26.74 and
      42.86%). CONCLUSIONS: In clinical practice, the prevalence of ID and the accuracy
      to detect functional ID are dependent on marker selection and its definition.
      Regarding the results of this work, for laboratory investigation of ID, however,
      we suggest using Thomas-plot analyses in combination with ferritin single-marker
      measurements to efficiently identify patients with ID.

PMID- 25980733
TI  - Effects of Metabolic Syndrome on the Outcome of Carpal Tunnel Release: A Matched
      Case-Control Study.
AB  - PURPOSE: To compare outcomes of carpal tunnel release in patients with or without
      metabolic syndrome. METHODS: In a prospective consecutive series, 35 patients
      with metabolic syndrome and surgically treated carpal tunnel syndrome (CTS) were
      age- and sex- matched with 37 control patients without metabolic syndrome. Grip,
      pinch strength, perception of touch with Semmes-Weinstein monofilament, and
      Boston Carpal Tunnel Questionnaires (BCTQ) were assessed preoperatively and at 3,
      6, and 12 months postoperatively. RESULTS: Patients with metabolic syndrome had
      more severe electrophysiologic grade of CTS than those without metabolic
      syndrome, but the 2 groups had similar preoperative grip/pinch strength and BCTQ
      scores. The BCTQ symptom score for the metabolic syndrome group was significantly
      greater than that of the control group at 3 months, and the BCTQ function score
      of the metabolic syndrome group was significantly greater than that of the
      control group at 3 and 6 months' follow-up. However, there was no significant
      difference in BCTQ symptom or functional scores between groups at 12 months'
      follow-up. There was no significant difference in grip strength between groups
      through 12 months' follow-up whereas the pinch strength of the control group was
      significantly greater than that of the metabolic syndrome group at 12 months'
      follow-up. Semmes-Weinstein monofilament test results were significantly greater
      in the control group than in the metabolic syndrome group at 3 and 6 months'
      follow-up but were similar at 12 months. CONCLUSIONS: Patients with CTS and
      metabolic syndrome have delayed functional recovery after carpal tunnel release,
      but noteworthy improvements in symptom severity and hand function are similar to
      those in patients without metabolic syndrome 1 year after surgery. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 25980734
TI  - Biomechanical Comparison of 2 Methods of Intramedullary K-Wire Fixation of
      Transverse Metacarpal Shaft Fractures.
AB  - PURPOSE: To determine the relative importance of intramedullary wire (IMW)
      diameter and IMW number in conferring stability to a metacarpal fracture fixation
      construct. Our research hypothesis was that the stiffness of IMW fixation for
      metacarpal shaft fractures using a single 1.6-mm-diameter (0.062-in) wire would
      be greater than three 0.8-mm-diameter (0.031-in) wires. METHODS: Our study
      compared the biomechanical stiffness between one 1.6-mm K-wire and three 0.8-mm K
      wires in a composite, fourth-generation, biomechanical metacarpal construct under
      cantilever testing to treat transverse metacarpal shaft fractures. Six composite
      bone-wire constructs were tested in each group using constant-rate,
      nondestructive testing. Stiffness (load/displacement) was measured for each
      construct. RESULTS: All constructs demonstrated a linear load-displacement
      relationship. Wires were all tested in their elastic zone. The mean stiffness of
      the 1-wire construct was 3.20 N/mm and the mean stiffness of the 3-wire construct
      was 0.76 N/mm. These differences were statistically significant with a large
      effect size. CONCLUSIONS: The stiffness of IMW fixation for metacarpal shaft
      fractures using a single 1.6-mm-diameter wire was significantly greater than
      using three 0.8-mm-diameter wires. CLINICAL RELEVANCE: When IMW fixation is
      clinically indicated for the treatment of metacarpal fractures, the increased
      stiffness of a single large-diameter construct provides more stability in the
      plane of finger flexion-extension.

PMID- 25980735
TI  - Effect of Time Interval Between Tumescent Local Anesthesia Infiltration and Start
      of Surgery on Operative Field Visibility in Hand Surgery Without Tourniquet.
AB  - PURPOSE: To determine the optimal time interval between tumescent local
      anesthesia infiltration and the start of hand surgery without a tourniquet for
      improved operative field visibility. METHODS: Patients aged 16 to 60 years who
      needed contracture release and tendon repair in the hand were enrolled from the
      outpatient clinic. Patients were randomized to 10-, 15-, or 25-minute intervals
      between tumescent anesthetic solution infiltration (0.18% lidocaine and 1:221,000
      epinephrine) and the start of surgery. The end point of tumescence anesthetic
      infiltration was pale and firm skin. The surgical team was blinded to the time of
      anesthetic infiltration. At the completion of the procedure, the surgeon and the
      first assistant rated the operative field visibility as excellent, fair, or poor.
      We used logistic regression models without and with adjustment for confounding
      variables. RESULTS: Of the 75 patients enrolled in the study, 59 (79%) were
      males, 7 were randomized to 10-minute time intervals (further randomization was
      stopped after interim analysis found consistently poor operative field
      visibility), and 34 were randomized to the each of the 15- and 25-minute groups.
      Patients who were randomized to the 25-minute delay group had 29 times higher
      odds of having an excellent operative visual field than those randomized to the
      15-minute delay group. After adjusting for age, sex, amount of tumescent solution
      infiltration, and duration of operation, the odds ratio remained highly
      significant. CONCLUSIONS: We found that an interval of 25 minutes provides vastly
      superior operative field visibility; 10-minute delay had the poorest results.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 25980736
TI  - Trends in firearm safety-do they correlate with fewer injuries.
AB  - Firearm-related violence within the USA occurs at a much higher rate than other
      developed countries. While this rate is likely multifactorial in nature, a common
      debate within households and governments alike involves increased regulation of
      firearms in hopes of curtailing this violence. This article provides context in
      which to consider both the pros and cons of increased firearm regulation and a
      review of the effects certain regulations have had on firearm-related violence
      thus far. 

PMID- 25980737
TI  - Prescriber and patient-oriented behavioural interventions to improve use of
      malaria rapid diagnostic tests in Tanzania: facility-based cluster randomised
      trial.
AB  - BACKGROUND: The increasing investment in malaria rapid diagnostic tests (RDTs) to
      differentiate malarial and non-malarial fevers, and an awareness of the need to
      improve case management of non-malarial fever, indicates an urgent need for high
      quality evidence on how best to improve prescribers' practices. METHODS: A three
      arm stratified cluster-randomised trial was conducted in 36 primary healthcare
      facilities from September 2010 to March 2012 within two rural districts in
      northeast Tanzania where malaria transmission has been declining. Interventions
      were guided by formative mixed-methods research and were introduced in phases.
      Prescribing staff from all facilities received standard Ministry of Health RDT
      training. Prescribers from facilities in the health worker (HW) and health worker
      patient (HWP) arms further participated in small interactive peer-group training
      sessions with the HWP additionally receiving clinic posters and patient leaflets.
      Performance feedback and motivational mobile-phone text messaging (SMS) were
      added to the HW and HWP arms in later phases. The primary outcome was the
      proportion of patients with a non-severe, non-malarial illness incorrectly
      prescribed a (recommended) antimalarial. Secondary outcomes investigated RDT
      uptake, adherence to results, and antibiotic prescribing. RESULTS: Standard RDT
      training reduced pre-trial levels of antimalarial prescribing, which was
      sustained throughout the trial. Both interventions significantly lowered
      incorrect prescribing of recommended antimalarials from 8% (749/8,942) in the
      standard training arm to 2% (250/10,118) in the HW arm (adjusted RD (aRD) 4%; 95%
      confidence interval (CI) 1% to 6%; P = 0.008) and 2% (184/10,163) in the HWP arm
      (aRD 4%; 95% CI 1% to 6%; P = 0.005). Small group training and SMS were
      incrementally effective. There was also a significant reduction in the
      prescribing of antimalarials to RDT-negatives but no effect on RDT-positives
      receiving an ACT. Antibiotic prescribing was significantly lower in the HWP arm
      but had increased in all arms compared with pre-trial levels. CONCLUSIONS: Small
      group training with SMS was associated with an incremental and sustained
      improvement in prescriber adherence to RDT results and reducing over-prescribing
      of antimalarials to close to zero. These interventions may become increasingly
      important to cope with the wider range of diagnostic and treatment options for
      patients with acute febrile illness in Africa.

PMID- 25980738
TI  - Calculation of internal dose from ingested soil-derived uranium in humans:
      Application of a new method.
AB  - The aim of the present study was to determine the internal dose in humans after
      the ingestion of soil highly contaminated with uranium. Therefore, an in vitro
      solubility assay was performed to estimate the bioaccessibility of uranium for
      two types of soil. Based on the results, the corresponding bioavailabilities were
      assessed by using a recently published method. Finally, these bioavailability
      data were used together with the biokinetic model of uranium to assess the
      internal doses for a hypothetical but realistic scenario characterized by a daily
      ingestion of 10 mg of soil over 1 year. The investigated soil samples were from
      two former uranium mining sites of Germany with (238)U concentrations of about
      460 and 550 mg/kg. For these soils, the bioavailabilities of (238)U were
      quantified as 0.18 and 0.28 % (geometric mean) with 2.5th percentiles of 0.02 and
      0.03 % and 97.5th percentiles of 1.48 and 2.34 %, respectively. The corresponding
      calculated annual committed effective doses for the assumed scenario were 0.4 and
      0.6 uSv (GM) with 2.5th percentiles of 0.2 and 0.3 uSv and 97.5th percentiles of
      1.6 and 3.0 uSv, respectively. These annual committed effective doses are similar
      to those from natural uranium intake by food and drinking water, which is
      estimated to be 0.5 uSv. Based on the present experimental data and the selected
      ingestion scenario, the investigated soils-although highly contaminated with
      uranium-are not expected to pose any major health risk to humans related to
      radiation.

PMID- 25980740
TI  - The sweet quartet: Binding of fucose to the norovirus capsid.
AB  - Human noroviruses bind histo-blood group antigens (HBGAs) and this interaction is
      thought to be important for an infection. We identified two additional fucose
      binding pockets (termed fucose-3/4 sites) on a genogroup II human (GII.10)
      norovirus-protruding (P) dimer using X-ray crystallography. Fucose-3/4 sites were
      located between two previously determined HBGA binding pockets (termed fucose-1/2
      sites). We found that four fucose molecules were capable of binding altogether at
      fucose-1/2/3/4 sites on the P dimer, though the fucose molecules bound in a dose
      dependent and step-wise manner. We also showed that HBGA B-trisaccharide
      molecules bound in a similar way at the fucose-1/2 sites. Interestingly, we
      discovered that the monomers of the P dimer were asymmetrical in an unliganded
      state and when a single B-trisaccharide molecule bound, but were symmetrical when
      two B-trisaccharide molecules bound. We postulate that the symmetrical dimers
      might favor HBGA binding interactions at fucose-1/2 sites. 

PMID- 25980739
TI  - Cocaine promotes both initiation and elongation phase of HIV-1 transcription by
      activating NF-kappaB and MSK1 and inducing selective epigenetic modifications at
      HIV-1 LTR.
AB  - Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering
      specific cell-signaling and epigenetic pathways. We have elucidated the
      underlying molecular mechanisms through which cocaine exerts its effect in
      myeloid cells, a major target of HIV-1 in central nervous system (CNS). We
      demonstrate that cocaine treatment promotes HIV-1 gene expression by activating
      both nuclear factor-kappa B (NF-KB) and mitogen- and stress-activated kinase 1
      (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine
      10, and p65 subunit of NF-KB at 276th serine residue. These modifications enhance
      the interaction of NF-KB with P300 and promote the recruitment of the positive
      transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the
      development of an open/relaxed chromatin configuration, and facilitating the
      initiation and elongation phases of HIV-1 transcription. Results are also
      confirmed in primary monocyte derived macrophages (MDM). Overall, our study
      provides detailed insights into cocaine-driven HIV-1 transcription and
      replication. 

PMID- 25980741
TI  - Characterization of a large, proteolytically processed cowpox virus membrane
      glycoprotein conserved in most chordopoxviruses.
AB  - Most poxvirus proteins are either highly conserved and essential for basic steps
      in replication or less conserved and involved in host interactions. Homologs of
      the CPXV219 protein, encoded by cowpox virus, are present in nearly all
      chordopoxvirus genera and some species have multiple copies. The CPXV219 homologs
      have estimated masses of greater than 200 kDa, making them the largest known
      poxvirus proteins. We showed that CPXV219 was expressed early in infection and
      cleaved into N- and C-terminal fragments that remained associated. The protein
      has a signal peptide and transited the secretory pathway where extensive
      glycosylation and proteolytic cleavage occurred. CPXV219 was located by
      immunofluorescence microscopy in association with the endoplasmic reticulum,
      Golgi apparatus and plasma membrane. In non-permeabilized cells, CPXV219 was
      accessible to external antibody and biotinylation. Mutants that did not express
      CPXV219 replicated normally in cell culture and retained virulence in a mouse
      respiratory infection model.

PMID- 25980743
TI  - Strong relationship between vitamin D status and bone mineral density in anorexia
      nervosa.
AB  - BACKGROUND: Anorexia nervosa (AN) is associated with impaired bone health and low
      bone mineral density (BMD) as a consequence of an inadequate peak bone mass in
      adolescence and bone loss in young adulthood. The vitamin D status with its
      implications for bone health in patients affected by AN has only been examined
      previously in small studies. OBJECTIVE: To evaluate the prevalence of vitamin D
      deficiency and test the hypothesis that patients with AN and vitamin D deficiency
      might have worse bone metabolism and lower bone density as compared with AN with
      adequate vitamin D repletion. DESIGN: We analysed the vitamin D status and bone
      metabolism in a large cohort (n=89) of untreated patients affected by AN, with
      amenorrhoea. RESULTS: Vitamin D deficiency is widespread in untreated patients
      with AN: 16.9% had 25OH vitamin D levels below 12 ng/ml, 36% below 20 ng/ml and
      58.4% below 30 ng/ml. PTH values were higher and BMD at both femoral sites were
      lower in patients with vitamin D<20 ng/ml. Progressively higher values of BMD
      were observed by 4 ranks of 25 OH vitamin D values (severe deficiency: <12 ng/ml,
      deficiency: >=12 ng/ml and <20 ng/ml, insufficiency: >=20 and <30 ng/ml and
      normal: >=30 ng/ml). In patients with severe vitamin D deficiency BMD at the hip
      were significantly lower than that measured in groups with values over 20 ng/ml
      (p<0.001 for trend). The level of significance did not change for values adjusted
      for BMI or body weight. CONCLUSION: We found a strong relationship between
      vitamin D status and hip BMD values with additional benefits for those with 25OHD
      levels above 20 ng/ml. Our results support the design of a randomized placebo
      controlled clinical trial on the effect of vitamin D on BMD in patients with AN.
      The second point, whether 25OHD should be above 20 or 30 ng/ml remains a
      discussion point.

PMID- 25980742
TI  - Qualitative and quantitative validation of the FACIT-fatigue scale in iron
      deficiency anemia.
AB  - BACKGROUND: Fatigue is a burdensome symptom in iron deficiency anemia (IDA). To
      capture the severity and impact of fatigue appropriately it must be measured
      using validated scales. This study evaluated the content validity and
      psychometric validity of the Functional Assessment of Chronic Illness Therapy -
      fatigue scale (FACIT-fatigue) in IDA patients. METHODS: Qualitative patient
      interviews were conducted in the United States to evaluate content validity. The
      psychometric properties of the FACIT-fatigue scale were investigated using data
      from a phase 3 clinical trial assessing ferumoxytol in patients with a history of
      unsatisfactory oral iron therapy or in whom oral iron cannot be used. The
      statistical analysis assessed the acceptability, reliability, validity and
      responsiveness of the FACIT-fatigue scale. RESULTS: Qualitative interviews showed
      that fatigue is a central concern to IDA patients and that the FACIT-fatigue
      scale sufficiently assessed this construct. Psychometric assessment demonstrated
      that the FACIT-fatigue scale was stable over time (ICC = 0.87) and internally
      consistent (alpha = 0.93). The scale demonstrated convergence with other
      conceptually relevant scales such as SF-36 Vitality (r = 0.74), and distinguished
      between known groups [i.e., treatment arms (mean difference (95 % CI) = 3.56
      (1.68, 5.43), p <0.001) and high vs. low hemoglobin groups (mean difference (95 %
      CI) = 5.51 (8.59, 2.44) p <0.001)]. Responsiveness was also demonstrated;
      significant improvements in FACIT-fatigue scale scores corresponded with
      significant differences between minimal, moderate, and much improved vitality
      cohorts (p < 0.05). CONCLUSIONS: This research demonstrated that the FACIT
      fatigue scale has sound measurement properties and is an appropriate and
      interpretable assessment of fatigue among IDA patients with various underlying
      conditions.

PMID- 25980744
TI  - Matrix vesicles: Are they anchored exosomes?
AB  - Numerous studies have documented that matrix vesicles are unique extracellular
      membrane-bound microparticles that serve as initial sites for mineral formation
      in the growth plate and most other vertebrate mineralizing tissues. Microparticle
      generation is not confined to hard tissues, as cells in soft tissues generate
      similar structures; numerous studies have shown that a common type of
      extracellular particle, termed an exosome, a product of the endosomal pathway,
      shares many characteristics of matrix vesicles. Indeed, analyses of size,
      morphology and lipid and protein content indicate that matrix vesicles and
      exosomes are homologous structures. Such a possibility impacts our understanding
      of the biogenesis, processing and function of matrix vesicles (exosomes) in
      vertebrate hard tissues and explains in part how cells control the earliest
      stages of mineral deposition. Moreover, since exosomes influence a spectrum of
      functions, including cell-cell communication, it is suggested that this type of
      microparticle may provide a mechanism for the transfer of signaling molecules
      between cells within the growth plate and thereby regulate endochondral bone
      development and formation. 

PMID- 25980745
TI  - Image-guided core needle biopsy in the diagnosis of malignant lymphoma.
AB  - OBJECTIVE: Current European Society for Medical Oncology (ESMO) guidelines
      recommend that when feasible, surgical excision biopsy (SEB) is the ideal for
      diagnosis, sub-typing and grading of malignant lymphoma. We undertook this
      retrospective study to assess the diagnostic accuracy of image-guided core needle
      biopsy (CNB) in the diagnosis of malignant lymphoma, to identify the proportion
      of cases from which oncological treatment was subsequently instigated from the
      CNB diagnosis, and to evaluate the potential role for minimally invasive CNB
      techniques in the diagnostic pathway of malignant lymphoma. METHODS: All cases of
      lymphoma amenable to CNB between 2008 and 2013 were included. Patient records
      were reviewed to identify the biopsy diagnostic pathway undertaken (fine needle
      aspiration cytology, CNB, surgical excision biopsy). CNB specimens were graded as
      fully diagnostic (tumour sub-typing/grading and treatment initiated), partially
      diagnostic (diagnosis of lymphoma but more tissue required for sub
      typing/grading), equivocal or inadequate. The effects of anatomical location,
      needle gauge, number of core specimens and sub-type of disease on the diagnostic
      yield of the sample were analysed. RESULTS: 262 patients and 323 biopsy specimens
      were included in the study. 237 patients underwent CNB as the initial diagnostic
      intervention. In 230/237 CNB was fully diagnostic (97%), allowing initiation of
      treatment. In 7 patients, SEB was necessary in addition to CNB to provide
      additional diagnostic information to allow initiation of treatment. In 72
      patients, SEB was the only diagnostic test performed. CONCLUSION: Our study
      showed that in 97% of suitable cases, CNB provided sufficient diagnostic
      information to allow treatment of malignant lymphoma to be instigated. This
      minimally-invasive technique is well tolerated and has advantages over surgical
      techniques, including reduced costs, post-procedural complications and delays on
      the diagnostic pathway. CNB may obviate the use of surgical techniques in the
      majority of suitable cases, however its success is dependent on close
      collaboration and acceptance by clinicians and pathologists.

PMID- 25980746
TI  - Non-surgical complications after laparoscopic and open surgery for colorectal
      cancer - A systematic review of randomised controlled trials.
AB  - BACKGROUND: Cardiac and pulmonary complications account for a large part of
      postoperative mortality, especially in the growing number of elderly patients.
      This review studies the effect of laparoscopic surgery for colorectal cancer on
      short term non-surgical morbidity. METHODS: A literature search was conducted to
      identify randomised trials on laparoscopic compared to open surgery for
      colorectal cancer with reported cardiac or pulmonary complications. RESULTS: The
      search retrieved 3302 articles; 18 studies were included with a total of 6153
      patients. Reported median or mean age varied from 56 years to 72 years. The
      percentage of included patients with ASA-scores >= 3 ranged from 7% to 38%.
      Morbidity was poorly defined. Overall reported incidence of postoperative cardiac
      complications was low for both laparoscopic and open colorectal resection (median
      2%). There was a trend towards fewer cardiac complications following laparoscopic
      surgery (OR 0.66, 95% CI 0.41-1.06, p = 0.08), and this effect was most marked
      for laparoscopic colectomy (OR 0.28, 95% CI 0.11-0.71, p = 0.007). Incidence of
      pulmonary complications ranged from 0 to 11% and no benefit was found for
      laparoscopic surgery, although a possible trend was seen in favour of
      laparoscopic colectomy (OR 0.78, 95% CI 0.53-1.13, p = 0.19). Overall morbidity
      rates varied from 11% to 69% with a median of 33%. CONCLUSION: Although morbidity
      was poorly defined, for laparoscopic colectomies, significantly less cardiac
      complications occurred compared with open surgery and a trend towards less
      pulmonary complications was observed. Subgroup analysis from two RCTs suggests
      that elderly patients benefit most from a laparoscopic approach based on overall
      morbidity rates.

PMID- 25980747
TI  - Uncertainties in the management of melanoma nodal metastasis.

PMID- 25980748
TI  - Age stratified comparative analysis of perioperative, functional and oncologic
      outcomes in patients after robot assisted radical prostatectomy--A propensity
      score matched study.
AB  - INTRODUCTION AND OBJECTIVES: Our goal was to evaluate the perioperative,
      functional and intermediate term oncological outcomes of robot assisted radical
      prostatectomy (RARP) in patients >= 70 years. MATERIALS AND METHODS: The study
      population (N = 3241) consisted of consecutive patients who underwent RARP for
      localized prostate cancer by a single surgeon (VP) from January 2008 through
      February 2012. A query of our Institutional Review Board approved registry
      identified 400 men >= 70 years of age, with good functional status (Charlson co
      morbidity index < 3). These patients were propensity score matched to younger
      patients. Perioperative and postoperative functional and oncologic outcomes for
      the two groups were compared. RESULTS: Full nerve sparing as well as the ease of
      nerve sparing were similar in 2 groups. Intra-operative complications were
      comparable. Postoperative complication occurrence rates were similar. At mean
      follow up of 34.1 months and 37.2 months respectively in younger and older
      patients, the continence rate was comparable in 2 groups (91.3% and
      87.3%).Average time to continence and potency were similar in 2 groups. A greater
      proportion of younger patients became potent than elderly (52.3% vs 33.5%,p <
      0.001).The biochemical recurrence (BCR) rate was comparable in 2 groups (7.8% vs
      8.3%; p = 0.79). The mean time to BCR was also comparable in 2 groups (16 months
      vs 22.6 months; p = 0.07). CONCLUSIONS: In appropriately selected patients
      (minimal comorbidities with CCI <= 2, life expectancy >10 years, localized
      prostate cancer) RARP is a reasonable option in patients >= 7 0 years and
      provides comparable perioperative, functional and intermediate term oncologic
      outcomes as compared to younger patients.

PMID- 25980749
TI  - Viral and atypical bacterial aetiologies of infection in hospitalised patients
      admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia.
AB  - BACKGROUND: Influenza constitutes a leading cause of morbidity and mortality
      worldwide. There is limited information about the aetiology of infection
      presenting clinically as influenza in hospitalised adults and children in South
      East Asia. Such data are important for future management of respiratory
      infections. OBJECTIVES: To describe the aetiology of infection presenting
      clinically as influenza in those hospitalised in South-East Asia. METHODS:
      Respiratory specimens archived from July 2008 to June 2009 from patients
      hospitalised with suspected influenza from Indonesia, Thailand and Vietnam were
      tested for respiratory viruses and atypical bacteria by polymerase chain
      reaction. RESULTS: A total of 1222 patients' samples were tested. Of 1222, 776
      patients (63.5%) were under the age of 5. Viruses detected included rhinoviruses
      in 229 of 1222 patients (18.7%), bocaviruses in 200 (16.4%), respiratory
      syncytial viruses in 144 (11.8%), parainfluenza viruses in 140 (11.5%; PIV1: 32;
      PIV2: 12; PIV3: 71; PIV4: 25), adenovirus in 102 (8.4%), influenza viruses in 93
      (7.6%; influenza A: 77; influenza B: 16) and coronaviruses in 23 (1.8%; OC43: 14;
      E229: 9). Bacterial pathogens were Mycoplasma pneumoniae (n = 33, 2.7%),
      Chlamydophila psittaci (n = 2), C. pneumoniae (n = 1), Bordetella pertussis (n =
      1) and Legionella pneumophila (n = 2). Overall, in-hospital case fatality rate
      was 29 of 1222 (2.4%). CONCLUSION: Respiratory viruses were the most commonly
      detected pathogens in patients hospitalised with a clinical suspicion of
      influenza. Rhinovirus was the most frequently detected virus, and M. pneumoniae,
      the most common atypical bacterium. The low number of detected influenza viruses
      demonstrates a low benefit for empirical oseltamivir therapy, unless during an
      influenza outbreak.

PMID- 25980750
TI  - Does the use of salmon frames as bait for lobster/crab creel fishing
      significantly increase the risk of disease in farmed salmon in Scotland?
AB  - Salmon farming is an important economic activity, and employer, particularly for
      remoter areas of Scotland; crustacean fisheries are also significant small
      businesses in these areas. Salmon frames (the head and spine that remain after
      evisceration and filleting) are sometimes used to bait the creel pots used to
      catch lobsters and crabs. These frames may contain pathogens that could
      potentially be spread to salmon farms in the vicinity of creel fisheries.
      Therefore, an analysis has been carried out for key pathogens of farmed salmon to
      assess the risks associated with this process. Infection of farms via creel bait
      requires that: (1) pathogens are present in salmon at harvest; (2) they are not
      removed from the salmon that used for bait during processing; (3) they transmit
      from creel pot baits to salmon farms. This last step is critical and leads to
      most of the uncertainty in results. Risk were assessed for 7 viruses, 3 bacteria,
      and 3 eukaryotic parasites of importance to salmon farming. A potentially
      significant risk was identified in association with disease control programmes if
      fish were filleted at a secondary processor; such a situation should arise only
      rarely. A very low risk, per event, was identified from imports, however, because
      of large numbers of Norwegian imports processed in the UK this risk is always
      present. Risks were at worst of low (disease control) or very low (imports)
      probability and are significant only because of the magnitude of consequences. 

PMID- 25980751
TI  - mTORC1 Up-Regulates GP73 to Promote Proliferation and Migration of Hepatocellular
      Carcinoma Cells and Growth of Xenograft Tumors in Mice.
AB  - BACKGROUND & AIMS: Levels of the Golgi protein 73 (GP73) increase during
      development of hepatocellular carcinoma (HCC); GP73 is a serum marker for HCC.
      However, little is known about the mechanisms or effects of GP73 during hepatic
      carcinogenesis. METHODS: GP73 was overexpressed from a retroviral vector in HepG2
      cells, which were analyzed in proliferation and migration assays. Xenograft
      tumors were grown from these cells in nude mice. The effects of monoclonal
      antibodies against GP73 were studied in mice and cell lines. GP73(-/-), GP73(+/
      ), and GP73(+/+) mice were given injections of diethylnitrosamine to induce liver
      injury. Levels of GP73 were reduced in MHCC97H, HCCLM3, and HepG2.215 cell lines
      using small hairpin RNAs; xenograft tumors were grown in mice from MHCC97H-small
      hairpin GP73 or MHCC97H-vector cells. We used microarray analysis to compare
      expression patterns between GP73-knockdown and control MHCC97H cells. We studied
      the effects of the mechanistic target of rapamycin (mTOR) inhibitor rapamycin on
      GP73 expression in different cancer cell lines and on growth of tumors in mice.
      Levels of GP73 and activated mTOR were quantified in human HCC tissues. RESULTS:
      Xenograft tumors grown from HepG2 cells that expressed GP73 formed more rapidly
      and more metastases than control HepG2 cells in mice. A monoclonal antibody
      against GP73 reduced proliferation of HepG2 cells and growth of xenograft tumors
      in mice. GP73(-/-) mice had less liver damage after administration of
      diethylnitrosamine than GP73(+/-) or GP73(+/+) mice. In phosphatase and tensin
      homolog-null mouse embryonic fibroblasts with constitutively activated mTOR, GP73
      was up-regulated compared with control mouse embryonic fibroblasts; this increase
      was reversed after incubation with rapamycin. Expression of GP73 also was reduced
      in HCC and other cancer cell lines incubated with rapamycin. mTORC1 appeared to
      regulate expression of GP73 in cell lines. Activated mTOR correlated with the
      level of GP73 in human HCC tissues. Injection of rapamycin slowed the growth of
      xenograft tumors from MHCC97H-vector cells, compared with MHCC97H-short hairpin
      GP73 cells. CONCLUSIONS: Increased expression of GP73 promotes proliferation and
      migration of HCC cell lines and growth of xenograft tumors in mice. mTORC1
      regulates the expression of GP73, so GP73 up-regulation can be blocked with
      rapamycin. mTOR inhibitors or other reagents that reduce the level or activity of
      GP73 might be developed for the treatment of HCC.

PMID- 25980752
TI  - Exposure to Radiocontrast Agents Induces Pancreatic Inflammation by Activation of
      Nuclear Factor-kappaB, Calcium Signaling, and Calcineurin.
AB  - BACKGROUND & AIMS: Radiocontrast agents are required for radiographic procedures,
      but these agents can injure tissues by unknown mechanisms. We investigated
      whether exposure of pancreatic tissues to radiocontrast agents during endoscopic
      retrograde cholangiopancreatography (ERCP) causes pancreatic inflammation, and
      studied the effects of these agents on human cell lines and in mice. METHODS: We
      exposed mouse and human acinar cells to the radiocontrast agent iohexol
      (Omnipaque; GE Healthcare, Princeton, NJ) and measured intracellular release of
      Ca(2+), calcineurin activation (using a luciferase reporter), activation of
      nuclear factor-kappaB (NF-kappaB, using a luciferase reporter), and cell necrosis
      (via propidium iodide uptake). We infused the radiocontrast agent into the
      pancreatic ducts of wild-type mice (C57BL/6) to create a mouse model of post-ERCP
      pancreatitis; some mice were given intraperitoneal injections of the calcineurin
      inhibitor FK506 before and after infusion of the radiocontrast agent. CnAbeta(-/
      ) mice also were used. This experiment also was performed in mice given infusions
      of adeno-associated virus 6-NF-kappaB-luciferase, to assess activation of this
      transcription factor in vivo. RESULTS: Incubation of mouse and human acinar
      cells, but not HEK293 or COS7 cells, with iohexol led to a peak and then plateau
      in Ca(2+) signaling, along with activation of the transcription factors NF-kappaB
      and nuclear factor of activated T cells. Suppressing Ca(2+) signaling or
      calcineurin with BAPTA, cyclosporine A, or FK506 prevented activation of NF
      kappaB and acinar cell injury. Calcineurin Abeta-deficient mice were protected
      against induction of pancreatic inflammation by iohexol. The calcineurin
      inhibitor FK506 prevented contrast-induced activation of NF-kappaB in pancreata
      of mice, this was observed by live imaging of mice given infusions of adeno
      associated virus 6-NF-kappaB-luciferase. CONCLUSIONS: Radiocontrast agents cause
      pancreatic inflammation in mice, via activation of NF-kappaB, Ca(2+) signaling,
      and calcineurin. Calcineurin inhibitors might be developed to prevent post-ERCP
      pancreatitis in patients.

PMID- 25980753
TI  - Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous
      Cell Neoplasia: An International Trial.
AB  - BACKGROUND & AIMS: Esophageal squamous cell neoplasia has a high mortality rate
      as a result of late detection. In high-risk regions such as China, screening is
      performed by Lugol's chromoendoscopy (LCE). LCE has low specificity, resulting in
      unnecessary tissue biopsy with a subsequent increase in procedure cost and risk.
      The purpose of this study was to evaluate the accuracy of a novel, low-cost, high
      resolution microendoscope (HRME) as an adjunct to LCE. METHODS: In this
      prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and
      2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed
      white-light endoscopy followed by LCE and HRME. All optical images were compared
      with the gold standard of histopathology. RESULTS: By using a per-biopsy
      analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832),
      specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45%
      (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall
      accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient
      analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16),
      specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%,
      100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136
      biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55
      patients (48%; 95% confidence interval, 38%-57%) could have been spared any
      biopsy. CONCLUSIONS: In this trial, HRME improved the accuracy of LCE for
      esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost
      effective optical biopsy adjunct to LCE, potentially reducing unnecessary
      biopsies and facilitating real-time decision making in globally underserved
      regions. ClinicalTrials.gov, NCT 01384708.

PMID- 25980754
TI  - Identification of a Variety of Mutations in Cancer Predisposition Genes in
      Patients With Suspected Lynch Syndrome.
AB  - BACKGROUND & AIMS: Multigene panels are commercially available tools for
      hereditary cancer risk assessment that allow for next-generation sequencing of
      numerous genes in parallel. However, it is not clear if these panels offer
      advantages over traditional genetic testing. We investigated the number of cancer
      predisposition gene mutations identified by parallel sequencing in individuals
      with suspected Lynch syndrome. METHODS: We performed germline analysis with a 25
      gene, next-generation sequencing panel using DNA from 1260 individuals who
      underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All
      patients had a history of Lynch syndrome-associated cancer and/or polyps. We
      classified all identified germline alterations for pathogenicity and calculated
      the frequencies of pathogenic mutations and variants of uncertain clinical
      significance (VUS). We also analyzed data on patients' personal and family
      history of cancer, including fulfillment of clinical guidelines for genetic
      testing. RESULTS: Of the 1260 patients, 1112 met National Comprehensive Cancer
      Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval
      [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch
      syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other
      cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had
      mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch
      syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P =
      .0017). An additional 9 individuals carried mutations in other genes linked to
      high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations
      in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria
      for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%;
      95% CI, 35%-41%). CONCLUSIONS: In individuals with suspected Lynch syndrome,
      multigene panel testing identified high-penetrance mutations in cancer
      predisposition genes, many of which were unexpected based on patients' histories.
      Parallel sequencing also detected a high number of potentially uninformative
      germline findings, including VUS.

PMID- 25980756
TI  - Preserving double equipoise in living donor liver-kidney transplantation for
      primary hyperoxaluria type 1.

PMID- 25980755
TI  - Delayed Gastric Emptying Is Associated With Early and Long-term Hyperglycemia in
      Type 1 Diabetes Mellitus.
AB  - BACKGROUND & AIMS: After the Diabetes Control and Complications Trial (DCCT), the
      Epidemiology of Diabetes Interventions and Complications (EDIC) study continued
      to show persistent benefit of prior intensive therapy on neuropathy, retinopathy,
      and nephropathy in type 1 diabetes mellitus (DM). The relationship between
      control of glycemia and gastric emptying (GE) is unclear. METHODS: We assessed GE
      with a (13)C-spirulina breath test and symptoms in 78 participants with type 1
      diabetes at year 20 of EDIC. The relationship between delayed GE and glycated
      hemoglobin (HbA1c), complications of DM, and gastrointestinal symptoms were
      evaluated. RESULTS: GE was normal (37 participants; 50%), delayed (35
      participants; 47%), or rapid (2 participants; 3%). The latest mean HbA1c was
      7.7%. In univariate analyses, delayed GE was associated with greater DCCT
      baseline HbA1c and duration of DM before DCCT (P <= .04), greater mean HbA1c over
      an average of 27 years of follow-up evaluation (during DCCT-EDIC, P = .01), lower
      R-R variability during deep breathing (P = .03) and severe nephropathy (P = .05),
      and a greater composite upper gastrointestinal symptom score (P < .05). In
      multivariate models, retinopathy was the only complication of DM associated with
      delayed GE. Separately, DCCT baseline HbA1c (odds ratio [OR], 1.6; 95% confidence
      interval [CI], 1.1-2.3) and duration of DM (OR, 1.2; 95% CI, 1.01-1.3) before
      DCCT entry and mean HbA1c during DCCT-EDIC (OR, 2.2; 95% CI, 1.04-4.5) were
      associated independently with delayed GE. CONCLUSIONS: In the DCCT/EDIC study,
      delayed GE was remarkably common and associated with gastrointestinal symptoms
      and with measures of early and long-term hyperglycemia. ClinicalTrials.gov
      numbers NCT00360815 and NCT00360893.

PMID- 25980757
TI  - [Multidimensional measurement of precarious employment: social distribution and
      its association with health in Catalonia (Spain)].
AB  - OBJECTIVE: To show the prevalence of precarious employment in Catalonia (Spain)
      for the first time and its association with mental and self-rated health,
      measured with a multidimensional scale. METHOD: A cross-sectional study was
      conducted using data from the II Catalan Working Conditions Survey (2010) with a
      subsample of employed workers with a contract. The prevalence of precarious
      employment using a multidimensional scale and its association with health was
      calculated using multivariate log-binomial regression stratified by gender.
      RESULTS: The prevalence of precarious employment in Catalonia was high (42.6%).
      We found higher precariousness in women, youth, immigrants, and manual and less
      educated workers. There was a positive gradient in the association between
      precarious employment and poor health. CONCLUSIONS: Precarious employment is
      associated with poor health in the working population. Working conditions surveys
      should include questions on precarious employment and health indicators, which
      would allow monitoring and subsequent analyses of health inequalities.

PMID- 25980758
TI  - Neandertal energetics: Uncertainty in body mass estimation limits comparisons
      with Homo sapiens.

PMID- 25980760
TI  - Mammalian RNA virus-derived small RNA: biogenesis and functional activity.
AB  - The role of virus-derived small RNAs (vsRNAs) has been identified as an antiviral
      mechanism in plants, arthropods, and nematodes. Although mammalian DNA viruses
      have been observed to encode functional miRNAs, whether RNA virus infection
      generates functional vsRNAs remains under discussion. This article reviews the
      most recent reports regarding pathways for generating vsRNAs and the identified
      vsRNA activity in mammalian cells infected with RNA viruses. We also discuss
      several hypotheses regarding the roles of mammalian vsRNAs and comment on the
      potential directions for this research field. 

PMID- 25980759
TI  - Single amino acid substitution (G42E) in the receptor binding domain of mouse
      mammary tumour virus envelope protein facilitates infection of non-murine cells
      in a transferrin receptor 1-independent manner.
AB  - BACKGROUND: Mouse mammary tumour virus (MMTV) is a betaretrovirus that infects
      rodent cells and uses mouse tranferrin receptor 1 (TfR1) for cell entry. Several
      MMTV strains have been shown to productively infect, in addition to murine cells,
      various heterologous cell lines including those of human origin, albeit less
      efficiently than murine cells. Furthermore, there have been reports that the
      continued passage of MMTV in heterologous cell lines gives rise to novel variants
      that are able to infect naive non-murine cells with higher efficiency than the
      parental virus. RESULTS: We show that MMTV(C3H), like other MMTV strains, that
      had undergone a number of replication cycles in non-murine cells displayed an
      increased replication kinetic, as compared to parental virus, when applied on
      naive human cells. Sequence analysis of several replication kinetic variants and
      the parental virus, together with calculation of the ratio of non-synonymous to
      synonymous mutations at individual codons, revealed that several regions within
      the viral genome were under strong positive selection pressure during viral
      replication in human cells. The mutation responsible, at least in part, for the
      phenotypic change was subsequently mapped to the segment of env encoding the
      receptor binding site (F40HGFR44). Introduction of the identified mutation,
      leading to single amino acid substitution (G42E), into egfp-containing
      recombinant MMTV virions enhanced their ability to bind to and infect human
      cells. Interestingly, neither the replication kinetic mutant nor the parental
      virus required human TfR1 for infection. Knock-out of TFR1 gene from the human
      genome did not decrease the susceptibility of Hs578T cells to virus infection.
      Furthermore, the expression of human TfR1, in contrast to mouse TfR1, did not
      enhance the susceptibility of MMTV-resistant Chinese hamster ovary cells. Thus,
      human TfR1 is dispensable for infection and another cell surface molecule
      mediates the MMTV entry into human cells. CONCLUSION: Taken together, our data
      explain the mechanism enabling MMTV to form 'host-range variants' in non-murine
      cells that has been known for a long time, the basis of which remained obscure.
      Our findings may expand our understanding of how viruses gain capability to cross
      species-specific barriers to infect new hosts.

PMID- 25980761
TI  - Hepatitis C treatment and quality of life - You can't always get what you want,
      but you might get what you need.

PMID- 25980762
TI  - Statin use and non-alcoholic steatohepatitis in at risk individuals.
AB  - BACKGROUND & AIMS: Excess hepatic free cholesterol contributes to the
      pathogenesis of non-alcoholic steatohepatitis, and statins reduce cholesterol
      synthesis. Aim of this study was to assess whether statin use is associated with
      histological liver damage related to steatohepatitis. METHODS: The relationship
      between statin use, genetic risk factors, and liver damage was assessed in a
      multi-center cohort of 1201 European individuals, who underwent liver biopsy for
      suspected non-alcoholic steatohepatitis. RESULTS: Statin use was recorded in 107
      subjects, and was associated with protection from steatosis, NASH, and fibrosis
      stage F2-F4, in a dose-dependent manner (adjusted p<0.05 for all). In 100 treated
      patients matched 1:1 for modality of recruitment, gender, presence of IFG or type
      2 diabetes, PNPLA3 I148M risk alleles, TM6SF2 E167K variant, age, and BMI, statin
      use remained associated with protection from steatosis (OR 0.09, 95% C.I. 0.01
      0.32; p=0.004), steatohepatitis (OR 0.25, 95% C.I. 0.13-0.47; p<0.001), and
      fibrosis stage F2-F4 (OR 0.42, 95% C.I. 0.20-0.8; p=0.017). Results were
      confirmed in a second analysis, where individuals were matched within recruitment
      center (p<0.05 for all). The protective effect of statins on steatohepatitis was
      stronger in subjects not carrying the I148M PNPLA3 risk variant (p=0.02 for
      interaction), as statins were negatively associated with steatohepatitis in
      patients negative (p<0.001), but not in those positive for the I148M variant
      (p=n.s.). CONCLUSIONS: Statin use was associated with protection towards the full
      spectrum of liver damage in individuals at risk of non-alcoholic steatohepatitis.
      However, the I148M PNPLA3 risk variant limited this beneficial effect.

PMID- 25980763
TI  - Reply to: "New imaging assisted methods for liver fibrosis quantification: Is it
      really favorable to classical transient elastography?".

PMID- 25980764
TI  - EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early
      recurrence of hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) continue
      to have a dismal prognosis. Early recurrence, metastases and angiogenesis are the
      major obstacles to improve the outcome of HCC. Epithelial-mesenchymal transition
      (EMT) is a key contributor to cancer metastasis and recurrence, which are the
      major obstacles to improve prognosis of HCC. METHODS: Combining gene expression
      profiles of HCC samples with or without early recurrence and established cell
      lines with epithelial or mesenchymal phenotype, EDIL3 was identified as a novel
      regulator of EMT. The expression of EDIL3 was evaluated by quantitative PCR,
      Western blotting or immunohistochemistry. The effects of EDIL3 on the
      angiogenesis and metastasis of HCC cells were examined by wound healing, Matrigel
      invasion and tube formation assay in vitro and orthotopic xenograft mouse model
      of HCC in vivo. The signaling pathways of EDIL3 mediated were investigated
      through microarray and Western blotting analysis. RESULTS: EDIL3 was identified
      as a novel regulator of EMT, which contributes to angiogenesis, metastasis and
      recurrence of HCC. EDIL3 induces EMT and promotes HCC migration, invasion and
      angiogenesis in vitro. Mechanistically, overexpression of EDIL3, which was
      regulated by the downregulation of miR-137 in HCC, triggered the activation of
      ERK and TGF-beta signaling through interactions with alphavbeta3 integrin.
      Blocking ERK and TGF-beta signaling overcomes EDIL3 induced angiogenesis and
      invasion. Using the orthotopic xenograft mouse model of HCC, we demonstrated that
      EDIL3 enhanced the tumorigenic, metastatic and angiogenesis potential of HCC in
      vivo. CONCLUSIONS: EDIL3-mediated activation of TGF-beta and ERK signaling could
      provide therapeutic implications for HCC.

PMID- 25980765
TI  - Detection of telomerase activity using microchip electrophoresis.
AB  - Telomerase participates in malignant transformation or immortalization of cells
      and thus has attracted attention as an anticancer drug target and diagnostic
      tumor marker. The telomeric repeat amplification protocol (TRAP) and improved
      TRAP methods (TRAP-fluorescence, TRAP-hybridization, etc.) are widely used forms
      of this telomerase assay. However, these approaches generally employ acrylamide
      gel electrophoresis after amplification of telomeric repeats by polymerase chain
      reaction (PCR), making these TRAP methods time consuming and technically
      demanding. In this study we developed a novel telomerase assay using microchip
      electrophoresis for rapid and highly sensitive detection of telomerase activity
      in cancer cells. The mixed gel of 0.8% hydroxypropyl methylcellulose (HPMC) and
      0.3% polyethylene oxide (PEO) with SYBR Gold (fluorescent reagent) was used for
      microchip electrophoresis. As a result, the product amplified by a telomerase
      positive cell could be measured in one cell per assay and detected with high
      reproducibility (CV=0.67%) in the short time of 100s. 

PMID- 25980767
TI  - Metal ion clip: fine-tuning aromatic stacking interactions in the multistep
      formation of carbazole-bridged zinc(II) complexes.
AB  - A carbazole-based triple bridging ligand (LH) consisting of two imidazole
      moieties at 3,6 positions with a diketone unit at the carbazole nitrogen forms
      carbazole-bridged zinc(II) complexes with structures of [(L(-))4(Zn(2+))n] (n = 2
      6), where the strength of aromatic stacking interactions between the carbazole
      rings increases with an increase in the number of Zn(2+) ions bridged by the
      imidazole moieties.

PMID- 25980766
TI  - A prognostic score to identify low-risk outpatients with acute deep vein
      thrombosis in the upper extremity.
AB  - BACKGROUND: No studies have identified which patients with upper-extremity deep
      vein thrombosis (DVT) are at low risk for adverse events within the first week of
      therapy. METHODS: We used data from Registro Informatizado de la Enfermedad
      TromboEmbolica to explore in patients with upper-extremity DVT a prognostic score
      that correctly identified patients with lower limb DVT at low risk for pulmonary
      embolism, major bleeding, or death within the first week. RESULTS: As of December
      2014, 1135 outpatients with upper-extremity DVT were recruited. Of these, 515
      (45%) were treated at home. During the first week, three patients (0.26%)
      experienced pulmonary embolism, two (0.18%) had major bleeding, and four (0.35%)
      died. We assigned 1 point to patients with chronic heart failure, creatinine
      clearance levels 30-60 mL min(-1) , recent bleeding, abnormal platelet count,
      recent immobility, or cancer without metastases; 2 points to those with
      metastatic cancer; and 3 points to those with creatinine clearance levels < 30 mL
      min(-1) . Overall, 759 (67%) patients scored <= 1 point and were considered to be
      at low risk. The rate of the composite outcome within the first week was 0.26%
      (95% confidence interval [CI] 0.004-0.87) in patients at low risk and 1.86% (95%
      CI 0.81-3.68) in the remaining patients. C-statistics was 0.73 (95% CI 0.57
      0.88). Net reclassification improvement was 22%, and integrated discrimination
      improvement was 0.0055. CONCLUSIONS: Using six easily available variables, we
      identified outpatients with upper-extremity DVT at low risk for adverse events
      within the first week. These data may help to safely treat more patients at home.

PMID- 25980769
TI  - Arterial stiffness in patients with bronchial asthma; role of hypertension and
      antihypertensive drugs.

PMID- 25980770
TI  - Endoscopic closure of acquired oesophagorespiratory fistulas with cardiac septal
      defect occluders or vascular plugs.
AB  - OBJECTIVES: To report an endoscopic treatment for inoperable oesophagorespiratory
      fistulas (ORFs). PATIENTS AND METHODS: Six patients with inoperable acquired
      tracheobronchial-oesophageal fistulas (four males and two females; mean age, 70.2
      +/- 10.28 years) were included. Cardiac septal defect occluders or vascular plugs
      were implanted through a flexible bronchoscope to close the ORFs. Monthly follow
      ups were done for 16 months. RESULTS: All fistulas were successfully closed
      immediately after the procedure. The severe aspirated pneumonia was controlled in
      7-10 days. The two mechanically ventilated patients were weaned successfully from
      the ventilator, and the general condition of patients improved rapidly. However,
      the fistulas recanalised in four patients because of the cutting effect of the
      edge of the occluders 1-12 months after the procedure. Other reasons, such as
      compression of the tracheal intubation balloon and repeated inflammation of the
      oesophageal diverticulum, may also have contributed to the recanalisation.
      CONCLUSIONS: Endoscopic closure of acquired ORFs with cardiac septal defect
      occluders or vascular plugs improve patients' general condition immediately after
      the procedure, but may result in recanalisation longterm. The occlusion might be
      considered an abridgement to surgery.

PMID- 25980768
TI  - Anaplasma phagocytophilum prevalence in ticks and rodents in an urban and natural
      habitat in South-Western Slovakia.
AB  - BACKGROUND: Ixodes ricinus is the principal vector of Anaplasma phagocytophilum,
      the ethiological agent of granulocytic anaplasmosis in Europe. Anaplasmosis is an
      emerging zoonotic disease with a natural enzootic cycle. The reservoir competence
      of rodents is unclear. Monitoring of A. phagocytophilum prevalence in I. ricinus
      and rodents in various habitat types of Slovakia may contribute to the knowledge
      about the epidemiology of anaplasmosis in Central Europe. METHODS: Over 4400
      questing ixodid ticks, 1000 rodent-attached ticks and tissue samples of 606
      rodents were screened for A. phagocytophilum DNA by real-time PCR targeting the
      msp2 gene. Ticks and rodents were captured along six transects in an
      urban/suburban and natural habitat in south-western Slovakia during 2011-2014.
      Estimates of wildlife (roe deer, red deer, fallow deer, mouflon, wild boar)
      densities in the study area were taken from hunter's yearly reports. Spatial and
      temporal differences in A. phagocytophilum prevalence in questing I. ricinus and
      relationships with relative abundance of ticks and wildlife were analysed.
      RESULTS: Overall prevalence of A. phagocytophilum in questing I. ricinus was
      significantly higher in the urban/suburban habitat (7.2%; 95% CI: 6.1-8.3%)
      compared to the natural habitat (3.1%; 95% CI: 2.5-3.9%) (chi(2) = 37.451; P <
      0.001). Significant local differences in prevalence of infected questing ticks
      were found among transects within each habitat as well as among years and between
      seasons. The trapped rodents belonged to six species. Apodemus flavicollis and
      Myodes glareolus prevailed in both habitats, Microtus arvalis was present only in
      the natural habitat. I. ricinus comprised 96.3% of the rodent-attached ticks, the
      rest were Haemaphysalis concinna, Ixodes trianguliceps and Dermacentor
      reticulatus. Only 0.5% of rodent skin and 0.6% of rodent-attached ticks (only I.
      ricinus) were infected with A. phagocytophilum. Prevalence of A. phagocytophilum
      in questing I. ricinus did not correlate significantly with relative abundance of
      ticks or with abundance of wildlife in the area. CONCLUSION: The study confirms
      that urban I. ricinus populations are infected with A. phagocytophilum at a
      higher rate than in a natural habitat of south-western Slovakia and suggests that
      rodents are not the main reservoirs of the bacterium in the investigated area.

PMID- 25980772
TI  - Outcomes of repair of left partial anomalous pulmonary venous connection in
      children.
AB  - Herein, we report a case series of patients who underwent repair of left partial
      anomalous pulmonary venous connection (L-PAPVC) via anastomosing the anomalous
      pulmonary vein (PV) to the left atrial appendage. Fifteen children underwent
      repair of L-PAPVC between 1980 and 2014. The median age at surgery was 3.6 years
      (range: 5 days to 17.2 years). Concomitant anomalies were present in 87% (13/15).
      There were no early deaths. There was 1 late death occurring 63 days following
      surgical repair due to pneumococcal septicaemia in a patient with prior atrial
      septal defect closure and Ehlers-Danlos syndrome. The overall survival rate was
      93.7% at 15 years. A single patient (1/15, 7%) required reoperation 1 year after
      L-PAPVC repair for PV stenosis due to several thrombi located throughout the PV.
      The rate of freedom from PV reoperation was 90% at 10 years. The follow-up was
      100% complete with a median time of 11 years (range: 52 days to 20 years). To our
      knowledge, this is the youngest cohort of patients who have undergone surgical
      repair of L-PAPVC. Repair of L-PAPVC in children can be achieved via anastomosis
      of the anomalous vessel to the left atrial (LA) with excellent outcomes. The rate
      of anastomotic stenosis at the site of implantation on the LA is low. 

PMID- 25980771
TI  - Role for the banana AGAMOUS-like gene MaMADS7 in regulation of fruit ripening and
      quality.
AB  - MADS-box transcription factors play important roles in organ development. In
      plants, most studies on MADS-box genes have mainly focused on flower development
      and only a few concerned fruit development and ripening. A new MADS-box gene
      named MaMADS7 was isolated from banana fruit by rapid amplification of cDNA ends
      (RACE) based on a MADS-box fragment obtained from a banana suppression
      subtractive hybridization (SSH) cDNA library. MaMADS7 is an AGAMOUS-like MADS-box
      gene that is preferentially expressed in the ovaries and fruits and in tobacco
      its protein product localizes to the nucleus. This study found that MaMADS7
      expression can be induced by exogenous ethylene. Ectopic expression of MaMADS7 in
      tomato resulted in broad ripening phenotypes. The expression levels of seven
      ripening and quality-related genes, ACO1, ACS2, E4, E8, PG, CNR and PSY1 in
      MaMADS7 transgenic tomato fruits were greatly increased while the expression of
      the AG-like MADS-box gene TAGL1 was suppressed. Compared with the control, the
      contents of beta-carotene, lycopene, ascorbic acid and organic acid in
      transformed tomato fruits were increased, while the contents of glucose and
      fructose were slightly decreased. MaMADS7 interacted with banana 1
      aminocyclopropane-1-carboxylic acid (ACC) oxidase gene 1 (MaACO1) and tomato
      phytoene synthase gene (LePSY1) promoters. Our results indicated that MaMADS7
      plays an important role in initiating endogenous ethylene biosynthesis and fruit
      ripening. 

PMID- 25980773
TI  - A new method for the adjustment of neochordal length: the adjustable slip knot
      technique.
AB  - The use of expanded polytetrafluoroethylene (ePTFE) sutures for the correction of
      mitral valve prolapse has become a standardized procedure. Adjustment of
      neochordal length is crucial to the efficacy of this technique. Various methods
      have been described for this purpose; however, the fine adjustment of neochordal
      length is technically challenging. We describe a simple and effective technique
      for the implantation of neochordae, which we have termed the 'adjustable slip
      knot technique'. The first step of this technique is reinforcement of the
      papillary muscle by a Teflon pledget with or without polytetrafluoroethylene (CV
      4) loops. The second step is the formation of a neochordal loop by introducing an
      ePTFE suture between the affected mitral leaflet and the papillary muscle or
      ePTFE loops. The third step is the adjustment of the length of neochordae. The
      formation of a slip knot in one arm of the ePTFE suture is the pivot of this
      technique. The neochordal loop can be constricted by the application of tension
      to one arm of the suture. We applied this technique in 5 patients with
      satisfactory results. 

PMID- 25980774
TI  - Mitral valve repair for atrial functional mitral regurgitation in patients with
      chronic atrial fibrillation.
AB  - OBJECTIVES: Atrial functional mitral regurgitation (MR) has been recently
      described in patients with chronic atrial fibrillation (AF). However, the results
      of surgical mitral valve (MV) repair for this type of MR have not been
      comprehensively reported. Our study aimed to address this deficiency. METHODS: We
      retrospectively studied 10 chronic AF patients who underwent MV repair for atrial
      functional MR with normal left ventricular dimension and preserved left
      ventricular systolic function. All patients had chronic heart failure (HF)
      symptoms and at least one prior admission for HF complicated by severe MR.
      RESULTS: Ring annuloplasty was performed in all patients; the median ring size
      was 26 mm (range, 26-30 mm). Concomitant tricuspid valve repair was undertaken in
      all patients. Preoperatively, left atrial (LA) diameter on the parasternal long
      axis view, LA volume index and mitral annular diameter were 52 +/- 9 mm, 72 +/-
      26 ml/m(2) and 33 +/- 4 mm, respectively. There was no mortality and no re
      admission due to HF during follow-up (range, 10-52 months). MR at the most recent
      examination was mild or improved in degree in all patients. The LA volume index
      decreased from the preoperative period, measuring 48 +/- 17 ml/m(2) at the most
      recent period (P = 0.03). The New York Heart Association functional class
      dramatically improved from the preoperative period to the most recent period
      (from 3.0 +/- 0.7 to 1.2 +/- 0.4, P < 0.0001). CONCLUSIONS: Our results suggest
      that MV repair leads to reductions in MR, LA size and HF symptoms, and that it
      may prevent future HF events in patients with atrial functional MR.

PMID- 25980775
TI  - MODULUS Stem for Developmental Hip Dysplasia: Long-term Follow-up.
AB  - Between October 2001 and December 2010, 143 patients with developmental dysplasia
      underwent hip arthroplasty surgery using a conical stem with modular necks
      (MODULUS system, Lima Corporate, Villanova di San Daniele del Friuli, Italy).
      Thirty (21.0%) patients had both hips replaced, for a total of 173 implants. The
      mean age at the time of surgery was 55 years (range: 22-81 years). The mean
      follow-up was 87 months (range: 36-146 months); average Harris Hip Score
      increased from 42 (range: 23-65) preoperatively to 92 (range: 76-100) at the last
      follow-up. Stem revision was required in two cases. The MODULUS stem showed good
      long-term clinical and radiographic results, with a Kaplan-Meier survivorship of
      97.6% (95% CI: 94.8-100.0%) at 8 years.

PMID- 25980776
TI  - Total Hip Arthroplasty for Patients Who Have Ankylosing Spondylitis: Is
      Postoperative Irradiation Required for Prophylaxis of Heterotopic Ossification?
AB  - Postoperative radiation for prevention of heterotopic ossification (HO) has been
      proven effective for the patients with ankylosing spondylitis (AS) after total
      hip arthroplasties (THA). This study aims to evaluate the effect of postoperative
      radiation in HO formation following THA in patients with AS. We retrospectively
      reviewed 129 hips from 91 patients with AS receiving primary THA from July 2004
      to December 2012. There were total 38 patients (53 hips) did not receive
      postoperative prophylaxis in Group I. Moreover, 53 patients (76 hips) received
      postoperative single-fraction radiotherapy of 500 cGy in Group II. After a
      minimum 12-month follow-up, there was no significant difference in HO formation
      between the two groups (P=0.210). This study suggests that postoperative
      radiation may not be necessary in Asian patients. 

PMID- 25980777
TI  - A fully automatic reference deconvolution strategy to increase the accuracy of in
      vivo lipid signal quantification.
AB  - PURPOSE: Lipid signals measured by (1)H MR spectroscopy cannot be adequately
      quantified by common fitting routines like VARPRO or AMARES, if lipid spectra are
      distorted by irregular spatial and temporal inhomogeneities of the static
      magnetic field during readout. A fully automatic reference deconvolution
      algorithm is presented that eliminates these distortions before application of
      fitting routines. METHODS: The measured signal of the dominant methyl resonance
      is isolated with aid of a spectral estimator (estimation of parameters via
      rotational invariance techniques) and used as reference signal for estimation of
      distortions. A Wiener filter is applied to deconvolve those distortions in the
      lipid spectrum. Performance of the algorithm is assessed for different bandwidths
      and shapes of distortions, using artificially distorted as well as measured data.
      RESULTS: Application of the fully automatic reference deconvolution algorithm on
      simulated spectra yields a distinct increase in quantification accuracy.
      Deconvolved in vivo spectra of subcutaneous fat indicate reduced spectral overlap
      after application of the proposed strategy. CONCLUSION: The proposed method is
      helpful for in vivo magnetic resonance spectroscopy of adipose tissue to correct
      for effects of field inhomogeneities within the voxel and for inevitable eddy
      current effects. Quantification accuracy is improved by eliminating distortions
      before application of fitting routines.

PMID- 25980778
TI  - Association of Spontaneous Coronary Artery Dissection With Fibromuscular
      Dysplasia.

PMID- 25980780
TI  - Corneal cross-linking.
AB  - Since its inception in the late 1990s, corneal cross-linking has grown from an
      interesting concept to a primary treatment for corneal ectatic disease worldwide.
      Using a combination of ultraviolet-A light and a chromophore (vitamin B2,
      riboflavin), the cornea can be stiffened, usually with a single application, and
      progressive thinning diseases such as keratoconus arrested. Despite being in
      clinical use for many years, some of the underlying processes, such as the role
      of oxygen and the optimal treatment times, are still being worked out. More than
      a treatment technique, corneal cross-links represent a physiological principle of
      connective tissue, which may explain the enormous versatility of the method. We
      highlight the history of corneal cross-linking, the scientific underpinnings of
      current techniques, evolving clinical treatment parameters, and the use of cross
      linking in combination with refractive surgery and for the treatment of
      infectious keratitis. 

PMID- 25980781
TI  - Response to "Civil time ? biological time: Recent options for empirically testing
      possible effects of chronodisruption".

PMID- 25980782
TI  - Challenges in the diagnosis and management of cervical neuroendocrine carcinoma.
AB  - Neuroendocrine carcinoma represents about 1% all cervical cancers accounting for
      100-200 diagnoses annually in the USA. Although it is uncommon, it is an
      aggressive histologic subtype of this otherwise favorable disease. To date, there
      are no prospective studies or randomized trials specific to this disease to guide
      standard of care management. Published literature consists of small case series
      mostly describing single-institution experiences. The Society of Gynecologic
      Oncology and Gynecologic Cancer InterGroup have issued consensus guidelines about
      the treatment of this disease based on the existing retrospective literature and
      expert opinion. Ongoing research is focused on further clarifying the best
      treatment regimen and defining molecular alterations of these tumors that can be
      exploited by novel treatment mechanisms. The objective of this manuscript is to
      describe this entity, review the literature, summarize current treatment
      recommendations, and propose possible research efforts for women with
      neuroendocrine cervical cancer. 

PMID- 25980779
TI  - Angiogenesis in glaucoma filtration surgery and neovascular glaucoma: A review.
AB  - Angiogenesis may pose a clinical challenge in glaucoma, for example, during the
      wound healing phase after glaucoma filtration surgery and in the severe secondary
      glaucoma called neovascular glaucoma (NVG). Upregulation of vascular endothelial
      growth factor (VEGF), a key mediator of angiogenesis, occurs in eyes that have
      undergone glaucoma filtration surgery, as well as those with NVG. This has led
      investigation of the ability of anti-vascular endothelial growth factor therapy
      to improve outcomes, and we examine the findings with respect to the safety and
      efficacy of anti-vascular endothelial growth factor agents, mainly bevacizumab
      and ranibizumab, in eyes that have undergone glaucoma filtration surgery or have
      NVG. Combining conventional therapies-such as antimetabolites after filtration
      surgery and panretinal photocoagulation in NVG-and anti-vascular endothelial
      growth factor drugs may produce a synergetic effect, although further studies are
      required to evaluate the long-term efficacy of combination treatments. 

PMID- 25980783
TI  - Who is going to make the wise choice?
AB  - Inspired by the American Board of Internal Medicine's Choosing Wisely(r)
      campaign, a group of housestaff at Vanderbilt University Medical Center created
      the Vanderbilt Choosing Wisely Steering Committee (VCWSC) to explore ways to
      apply the campaign's principles of high value care to daily practice. In this
      article, we propose that housestaff leadership is key in the implementation of
      high value care initiatives at academic health centers (AHCs). We then describe
      the formation and activities of the VCWSC in the hope that our success will
      inspire residents at other AHCs to create similar initiatives.

PMID- 25980784
TI  - Attention and memory protection: Interactions between retrospective attention
      cueing and interference.
AB  - Visual working memory (VWM) and attention have a number of features in common,
      but despite extensive research it is still unclear how the two interact. Can
      focused attention improve VWM precision? Can it protect VWM from interference?
      Here we used a partial-report, continuous-response orientation memory task to
      examine how attention and interference affect different aspects of VWM and how
      they interact with one another. Both attention and interference were orthogonally
      manipulated during the retention interval. Attention was manipulated by
      presenting informative retro-cues, whereas interference was manipulated by
      introducing a secondary interfering task. Mixture-model analyses revealed that
      retro-cues, compared to uninformative cues, improved all aspects of performance:
      Attention increased recall precision and decreased guessing rate and swap-errors
      (reporting a wrong item in memory). Similarly, performing a secondary task
      impaired all aspects of the VWM task. In particular, an interaction between retro
      cue and secondary task interference was found primarily for swap-errors. Together
      these results suggest that both the quantity and quality of VWM representations
      are sensitive to attention cueing and interference modulations, and they
      highlight the role of attention in protecting the feature-location associations
      needed to access the correct items in memory. 

PMID- 25980785
TI  - Cooperative processing in primary somatosensory cortex and posterior parietal
      cortex during tactile working memory.
AB  - In the present study, causal roles of both the primary somatosensory cortex (SI)
      and the posterior parietal cortex (PPC) were investigated in a tactile unimodal
      working memory (WM) task. Individual magnetic resonance imaging-based single
      pulse transcranial magnetic stimulation (spTMS) was applied, respectively, to the
      left SI (ipsilateral to tactile stimuli), right SI (contralateral to tactile
      stimuli) and right PPC (contralateral to tactile stimuli), while human
      participants were performing a tactile-tactile unimodal delayed matching-to
      sample task. The time points of spTMS were 300, 600 and 900 ms after the onset of
      the tactile sample stimulus (duration: 200 ms). Compared with ipsilateral SI,
      application of spTMS over either contralateral SI or contralateral PPC at those
      time points significantly impaired the accuracy of task performance. Meanwhile,
      the deterioration in accuracy did not vary with the stimulating time points.
      Together, these results indicate that the tactile information is processed
      cooperatively by SI and PPC in the same hemisphere, starting from the early delay
      of the tactile unimodal WM task. This pattern of processing of tactile
      information is different from the pattern in tactile-visual cross-modal WM. In a
      tactile-visual cross-modal WM task, SI and PPC contribute to the processing
      sequentially, suggesting a process of sensory information transfer during the
      early delay between modalities. 

PMID- 25980786
TI  - Growth Control of MoS2 Nanosheets on Carbon Cloth for Maximum Active Edges
      Exposed: An Excellent Hydrogen Evolution 3D Cathode.
AB  - To greatly improve the hydrogen evolution reaction (HER) performance, it is the
      key approach to expose as many active edges of MoS2 as possible. This target is
      the research hotspot and difficulty of MoS2 which is a promising HER catalyst. In
      this work, we realized the active-edges control of MoS2 nanosheets on carbon
      cloth (CC) by growth control during the synthesis procedure. Moreover, MoS2
      nanosheets vertically grown on carbon cloth (MoS2?CC) was confirmed to be the
      best morphology with maximum active edges exposed. Multifactors structure control
      resulted in abundant active-edges exposure and effective electron delivery, thus
      excellent HER activity. This three-dimensional cathode, MoS2?CC, can reach a
      great current density of 200 mA/cm(2) at a small overpotential of 205 mV. The
      preeminent HER performance can rival the best MoS2-based catalyst ever reported. 

PMID- 25980787
TI  - Time study of staff members in an institution for severe motor and intellectual
      disabilities.
AB  - BACKGROUND: In Japan, improvement in the care for institutionalized patients with
      severe motor and intellectual disabilities (SMID) has resulted in improved
      prognosis compared with previous decades, leading to difficulty in entering
      institutions because of the limited capacity. In recent years, new SMID patients
      discharged mostly from neonatal intensive care units receive care in their
      parents' homes rather than in institutions. In order to effect this change, an
      assessment of patient care in both an institutional and home environment is of
      utmost importance. METHODS: We performed a minute-by-minute time study of the
      work of staff members (n = 31) in a ward in an institution for SMID (31 patients
      with no ventilators) over 48 h in order to reconstruct patient care. RESULTS:
      Significant differences were found between the entirely immobile group (n = 15)
      and semi-mobile group (n = 13) in the area of total care time (124.6 vs 83.4
      min/day, respectively, P = 0.003) and non-medical care time (99.1 vs 69.0
      min/day, P = 0.003). Nurses (16 in total) did twice as many tasks as other staff
      members in the areas of medical care and general care management. The number of
      tasks was the same for nurses and other staff members in the areas of non-medical
      care and social participation/others. CONCLUSION: Patient care undertaken by
      medical professionals in the areas of both ordinary care as well as medical care
      seemed to have contributed to improved prognosis in SMID patients. This study
      demonstrates the essential nature of nursing care for SMID patients living in
      institutions and at home.

PMID- 25980788
TI  - STED nanoscopy with fluorescent quantum dots.
AB  - The widely popular class of quantum-dot molecular labels could so far not be
      utilized as standard fluorescent probes in STED (stimulated emission depletion)
      nanoscopy. This is because broad quantum-dot excitation spectra extend deeply
      into the spectral bands used for STED, thus compromising the transient
      fluorescence silencing required for attaining super-resolution. Here we report
      the discovery that STED nanoscopy of several red-emitting commercially available
      quantum dots is in fact successfully realized by the increasingly popular 775 nm
      STED laser light. A resolution of presently ~ 50 nm is demonstrated for single
      quantum dots, and sub-diffraction resolution is further shown for imaging of
      quantum-dot-labelled vimentin filaments in fibroblasts. The high quantum-dot
      photostability enables repeated STED recordings with >1,000 frames. In addition,
      we have evidence that the tendency of quantum-dot labels to blink is largely
      suppressed by combined action of excitation and STED beams. Quantum-dot STED
      significantly expands the realm of application of STED nanoscopy, and, given the
      high stability of these probes, holds promise for extended time-lapse imaging.

PMID- 25980789
TI  - Influence of drug adherence and medical care on heart failure outcome in the
      primary care setting in Austria.
AB  - PURPOSE: Guideline-recommended therapy has been proven beneficial in heart
      failure (HF), but general implementation remains poor. The aim of this study was
      to evaluate the adherence to drug therapy, quality of primary non-drug medical
      care (NDMC) and its impact on HF outcome. METHODS: From 13 Austrian health
      insurance funds, we identified 36 829 patients (77.1 +/- 10.8 years, 44.8% men)
      hospitalised for HF who survived more than 90 days after discharge in the period
      between April 2006 and June 2010. Drug adherence was analysed from prescriptions
      filled and NDMC from numbers of physician consultations and diagnostic tests
      relevant for HF per quarter of a year (medical care index (MedCI)) claimed from
      the insurance funds. Kaplan-Meier and multivariate Cox regression analyses were
      performed to identify the association of outcome (survival and death without
      further admission for HF, readmission for HF) with drug adherence and NDMC.
      RESULTS: Readmission due to HF or death without prior readmission for HF occurred
      in 19.7% and 22.5%, respectively. Adherence to angiotensin-converting-enzyme
      inhibitors or angiotensin receptor blockers, beta-blockers and aldosterone
      antagonists was 49.3%, 40.4% and 16.1%, respectively, and was associated with
      better survival by Kaplan-Meier analysis. NDMC was consumed less frequently by
      deceased (76.0%; MedCI 2.55 +/- 3.04) than surviving (79.3%; 3.60 +/- 3.81) or
      readmitted (78.4%; 3.80 +/- 4.13) patients (p < 0.001 for deceased vs both
      other). Drug adherence and NDMC were independent factors associated with better
      survival by multivariate regression analysis. CONCLUSION: Guideline-recommended
      drug therapy remains underutilised in Austria. Drug adherence and quality of NDMC
      are associated with better outcome in HF patients.

PMID- 25980790
TI  - The Effects of Upper Limb Exercise Through Yoga on Limb Swelling in Chinese
      Breast Cancer Survivors - A Pilot Study.
AB  - PURPOSE: Breast cancer is the most common female cancer. The aim of this study
      was to assess the impact of yoga on lymphedema in breast cancer survivors.
      DESIGN: Repeated measures before and after the intervention. We enrolled 15 women
      with breast cancer who had not previously worn elastic clothing to treat
      lymphedema. METHODS: The program was led by a certified trainer and consisted of
      60-minute sessions, three times a week for 12 weeks. The volumes of the affected
      and normal limbs were measured. A self-assessed edema score was also recorded.
      FINDINGS: Fifteen patients completed the program, none of whom suffered from
      complications related to exercise. There was no significant edema after exercise.
      No significant differences were noted in subgroup analysis by age or the affected
      arm. CONCLUSIONS: Yoga does not induce lymphedema. CLINICAL RELEVANCE: Lymphedema
      is usually treated with uncomfortable elastic clothing, and high-resistance
      exercise may induce edema. Yoga may be suitable for these patients.

PMID- 25980791
TI  - Gonococcus - The culprit of refractory, severe conjunctivitis in an elderly
      patient.
AB  - We present a highly unusual case of microbiologically-confirmed adult gonococcal
      conjunctivitis in an elderly patient with the absence of genital co-infection and
      no sexual risk factors. Possible routes of infection are discussed, together with
      diagnosis and management of gonococcal keratoconjunctivitis. This case serves to
      highlight the possibility of gonococcal conjunctivitis as a diagnosis in severe,
      refractory conjunctivitis, even if the patient demographics, lack of pre-existing
      genital infection or sexual risk factors make gonococcus seem unlikely. 

PMID- 25980792
TI  - Induction of TNF-alpha signaling cascade in neonatal rat brain during propofol
      anesthesia.
AB  - Propofol anesthesia can trigger pro- and anti-apoptotic signaling pathways in the
      rat brain. In our previous work, we demonstrated that propofol causes widespread
      apoptotic neurodegeneration in 7-postnatal-day-old (PND7) but not in PND14 rat
      neurons. The mechanism responsible for these opposing outcomes is unknown,
      apparently linked to the specific stage of brain development. The present study
      aims to elucidate the anti-apoptotic process that is activated in the cortex and
      thalamus of PND14 Wistar rats during the first 48 h after the onset of propofol
      anesthesia. We showed that the expression of tumor necrosis factor-alpha (TNF
      alpha) and several components of its pathway, TNFR1 and caspase-8, was
      significantly increased in the cortex and thalamus. Nuclear factor kappa B (NF
      kappaB) p65 was downregulated in the cortex and upregulated in the thalamus. The
      expression of c-Fos was upregulated only in the cortex, showing opposed profile
      compared to NF-kappaB p65. Double immunofluorescence staining revealed the
      colocalization of NF-kappaB p65 with neuronal marker (NeuN), but with
      predominantly cytoplasmic localization. Finally, X-linked inhibitor of apoptosis
      protein (XIAP) was upregulated in both examined structures. Immunohistochemical
      staining with Iba-1 revealed that the treatment did not induce changes in
      microglial morphology. Our results (i) reveal that the simultaneous activation of
      pro- and anti-apoptotic signaling occurs after propofol anesthesia, and (ii)
      pinpoint the potential neuroprotective role of XIAP in anesthesia-induced
      neurotoxicity.

PMID- 25980793
TI  - Early-life stress increases the survival of midbrain neurons during postnatal
      development and enhances reward-related and anxiolytic-like behaviors in a sex
      dependent fashion.
AB  - Clinical studies have suggested that early-life stress (ELS) increases the risk
      of psychopathologies that are strongly associated with dysfunction of
      dopaminergic neurotransmission. Thus, ELS may interfere with the development and
      maturation of the dopaminergic system; however, the mechanisms involved in such
      interference are poorly understood. In the present study, we investigated the
      effect of ELS on the survival of specific populations of neurons in the
      substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) during
      postnatal development. First, we injected bromodeoxyuridine (BrdU) into pregnant
      rat dams on embryonic days 12, 13 and 14 to permanently label midbrain neurons.
      Then, after birth, the dams and litters were subjected to a maternal separation
      (MS) procedure to model ELS conditions. The number of BrdU+ neurons and the total
      number of neurons (cresyl violet+, CV+) were estimated in both male and female
      juvenile, adolescent, and adult rats. Moreover, sucrose preference and anxiety
      like behaviors were studied during adulthood. We found that MS permanently
      increased the number of BrdU+ and CV+ neurons in the VTA of males. In the SNc, a
      temporary increase in the number of BrdU+ neurons was observed in juvenile MS
      males; however, only adult MS males displayed an increase in the number of CV+
      neurons. Immunofluorescence analysis implied that MS affected the fate of non
      dopaminergic neurons. MS males displayed anxiolytic-like behavior and an increase
      in sucrose preference. These results suggest that ELS induces distinct
      dysregulation in the midbrain circuitry of males, which may lead to sex-specific
      psychopathology of the reward system. 

PMID- 25980794
TI  - Smaller Nanodiscs are Suitable for Studying Protein Lipid Interactions by
      Solution NMR.
AB  - Phospholipid bilayer nanodiscs, a newly developed model membrane system, provides
      "native-like" membrane environment for membrane protein studies. Nanodiscs
      assembled by membrane scaffold protein and phospholipid bilayer, with defined
      sizes that can be accurately regulated by changing the amino acid residues of the
      MSP construct. Herein we described the expression and purification of DeltaMSP, a
      deletion mutant of the membrane scaffold protein. Smaller nanodiscs with mixed
      lipids were assembled, and the observed (31)P NMR spectra showed identical
      chemical shifts to those of nanodiscs with pure POPC and POPE lipids, indicating
      they share similar chemical environments. The success of incorporation STIM1-TM
      into nanodiscs indicated the application of this smaller nanodisc system can be
      used to membrane protein studies by solution NMR. 

PMID- 25980795
TI  - Biochemical characterization of buffalo liver glucose-6-phosphate dehydrogenase
      isoforms.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme involved in
      the pentose phosphate pathway. This works represents purification of two buffalo
      liver glucose-6-phosphate dehydrogenases (BLG6PD1 and BLG6PD2) using combination
      of ammonium sulfate precipitation and several chromatographic columns. Both
      enzymes (BLG6PD1 and BLG6PD2) were homogenous on both native PAGE as well as 12%
      SDS PAGE with molecular weights of 28 and 66 kDa. The molecular weight of BLG6PD1
      and BLG6PD2 native forms were determined to be 28 and 66 kDa by gel filtration;
      indicating monomeric proteins. The K(m) values for BLG6PD1 and BLG6PD2 estimated
      to be 0.059 and 0.06 mM of beta-nicotinamide adenine dinucleotide phosphate. The
      optimum activity of BLG6PD1 and BLG6PD2 were displayed at pH 8.0 and 8.2 with an
      isoelectric point (pI) of pH 7.7-7.9 and 5.7-5.9. The divalent cations MgCl2, and
      CoCl2 act as activators, on the other hand, FeCl2, CuCl2 and ZnCl2 are potent
      inhibitors of BLG6PD1 and BLG6PD2 activity. NADPH inhibited both isoenzymes
      competitively with Ki values of 0.012 and 0.030 mM. This study describes a
      reproducible purification scheme of G6PD from the liver of buffalo as a rich
      source.

PMID- 25980796
TI  - Co-occurrence of pliopithecoid and hominoid primates in the fossil record: An
      ecometric analysis.
AB  - Both pliopithecoid and hominoid primates were widely distributed throughout
      Eurasia during the Miocene but are known to have coexisted at only a few
      localities. It has been speculated that their different habitat preferences
      permitted only minimal overlap under special environmental conditions. Here we
      study the context for pliopithecoid and hominoid co-occurrence by assessing
      taxonomically-based palaeoecological diversity of associated fossil mammals and
      by direct ecometric analysis based on hypsodonty of mammalian herbivores. Our
      results show that pliopithecoids persistently inhabited more humid environments
      compared to the other primate groups studied, suggesting an inability to adapt to
      changing environmental conditions. The opportunity for hominoids and
      pliopithecoids to co-occur appears to have been restricted by niche conservatism
      in the latter group. Our study also indicates that direct ecometric analysis
      gives a better separation of the ecological preferences of these primate clades
      than do analyses of taxonomically-based community structure. 

PMID- 25980797
TI  - Molluscan immunology.

PMID- 25980798
TI  - A manganese superoxide dismutase (MnSOD) from ark shell, Scapharca broughtonii:
      Molecular characterization, expression and immune activity analysis.
AB  - Manganese superoxide dismutase (MnSOD) is one of the key members of the
      antioxidant defense enzyme family, however, data regarding to the immune function
      of MnSOD in mollusks still remain limited now. In this study, a full-length MnSOD
      cDNA was identified by rapid amplification of cDNA ends (RACE) method from cDNA
      library of ark shell Scapharca broughtonii (termed SbMnSOD). The cDNA contained
      an open reading frame (ORF) of 696 bp which encoded a polypeptide of 232 amino
      acids, a 5'-UTR with length of 32 bp and a 3'-UTR of 275 bp. Four putative amino
      acid residues (His-57, His-105, Asp-190 and His-194) responsible for manganese
      coordination were located in the most highly conserved regions of SbMnSOD and the
      signature sequence (DVWEHAYY) also existed in SbMnSOD. The deduced amino acid
      sequence of SbMnSOD shared high homology to MnSOD from other species. All those
      data revealed that the SbMnSOD was a novel member of the MnSOD family. The mRNA
      expression profiles of SbMnSOD in tissues of foot, gill, mantle, adductor muscle,
      hemocytes and hepatopancreas analyzed by quantitative real-time PCR (qRT-PCR)
      suggested the mRNA transcripts of SbMnSOD distributed in all the examined
      tissues. Importantly, Vibrio anguillarum challenge resulted in the increased
      expression of SbMnSOD mRNA with a regular change trend in all examined tissues,
      indicating SbMnSOD actively participated in the immune response process. What's
      more, further analysis on the antibacterial activity of the recombinant SbMnSOD
      showed that the fusion protein could remarkably inhibit growth of both Gram
      positive and Gram-negative bacteria. The present results clearly suggested that
      SbMnSOD was an acute phase protein involved in the immune reaction in S.
      broughtonii.

PMID- 25980800
TI  - Experimental and theoretical investigations of the stereoselective synthesis of p
      stereogenic phosphine oxides.
AB  - An efficient enantioselective strategy for the synthesis of variously substituted
      phosphine oxides has been developed, incorporating the use of (1S,2S)-2
      aminocyclohexanol as the chiral auxiliary. The method relies on three key steps:
      1) Highly diastereoselective formation of P(V) oxazaphospholidine, rationalized
      by a theoretical study; 2) highly diastereoselective ring-opening of the
      oxazaphospholidine oxide with organometallic reagents that takes place with
      inversion of configuration at the P atom; 3) enantioselective synthesis of
      phosphine oxides by cleavage of the remaining P-O bond. Interestingly, the use of
      a P(III) phosphine precursor afforded a P-epimer oxazaphospholidine. Hence, the
      two enantiomeric phosphine oxides can be synthesized starting from either a P(V)
      or a P(III) phosphine precursor, which constitutes a clear advantage for the
      stereoselective synthesis of sterically hindered phosphine oxides.

PMID- 25980799
TI  - Antimnemonic effects of schemas in young and older adults.
AB  - Schema-consistent material that is aligned with an individual's knowledge and
      experience is typically more memorable than abstract material. This effect is
      often more extreme in older adults and schema use can alleviate age deficits in
      memory. In three experiments, young and older adults completed memory tasks where
      the availability of schematic information was manipulated. Specifying nonobvious
      relations between to-be-remembered word pairs paradoxically hindered memory
      (Experiment 1). Highlighting relations within mixed lists of related and
      unrelated word pairs had no effect on memory for those pairs (Experiment 2). This
      occurred even though related word pairs were recalled better than unrelated word
      pairs, particularly for older adults. Revealing a schematic context in a memory
      task with abstract image segments also hindered memory performance, particularly
      for older adults (Experiment 3). The data show that processing schematic
      information can come with costs that offset mnemonic benefits associated with
      schema-consistent stimuli. 

PMID- 25980801
TI  - Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine
      A Study with Felodipine as a Model Drug.
AB  - The aim of this study was to understand and predict the influence of hydrodynamic
      effects in the small intestine on dissolution of primary and aggregated drug
      particles. Dissolution tests of suspensions with a low-solubility drug,
      felodipine, were performed in a Couette cell under hydrodynamic test conditions
      corresponding to the fed small intestine. Dissolution was also performed in the
      USP II apparatus at two paddle speeds of 25 and 200 rpm and at different
      surfactant concentrations below critical micelle concentration. The experimental
      dissolution rates were compared with theoretical calculations. The different
      levels of shear stress in the in vitro tests did not influence the dissolution of
      primary or aggregated particles and experimental dissolution rates corresponded
      very well to calculations. The dissolution rate for the aggregated drug particles
      increased after addition of surfactant because of deaggregation, but there were
      still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence
      dissolution and deaggregation of micronized drug particles in the small intestine
      of this model drug. Surface tension has a strong effect on the deaggregation and
      subsequent dissolution. Addition of surfactants at in vivo relevant surface
      tension levels is thus critical for in vivo predictive in vitro dissolution
      testing.

PMID- 25980803
TI  - Management Dilemma in Acute Prosthetic Valve Thrombosis: Surgery or Thrombolysis?

PMID- 25980802
TI  - Early developmental stress negatively affects neuronal recruitment to avian song
      system nucleus HVC.
AB  - Adverse environmental conditions can impact the life history trajectory of
      animals. Adaptive responses enable individuals to cope with unfavorable
      conditions, but altered metabolism and resource allocation can bear long-term
      costs. In songbirds, early developmental stress can cause lifelong changes in
      learned song, a culturally transmitted trait, and nestlings experiencing
      developmental stress develop smaller song control nucleus HVCs. We investigated
      whether nutrition-related developmental stress impacts neurogenesis in HVC, which
      may explain how poor nutrition leads to smaller HVC volume. We provided different
      quality diets (LOW and HIGH) by varying the husks-to-seeds ratio to zebra finch
      families for the first 35 days after the young hatched (PHD). At PHD14-18 and
      again at nutritional independence (PHD35), juveniles were injected with different
      cell division markers. To monitor growth, we took body measures at PHD10, 17, and
      35. At PHD35 the number of newly recruited neurons in HVC and the rate of
      proliferation in the adjacent ventricular zone (VZ) were counted. Males raised on
      the LOW diet for their first weeks of life had significantly fewer new neurons in
      HVC than males raised on the HIGH diet. At the time when these new HVC neurons
      were born and labeled in the VZ (PHD17) the birds exposed to the LOW diet had
      significantly lower body mass. At PHD35 body mass or neuronal proliferation no
      longer differed. Our study shows that even transitory developmental stress can
      have negative consequences on the cellular processes underlying the development
      of neural circuits.

PMID- 25980805
TI  - Aggregation-induced photon upconversion through control of the triplet energy
      landscapes of the solution and solid states.
AB  - Aggregation-induced photon upconversion (iPUC) based on control of the triplet
      energy landscape is demonstrated for the first time. When a triplet state of a
      cyano-substituted 1,4-distyrylbenzene derivative is sensitized in solution, no
      upconverted emission based on triplet-triplet annihilation (TTA) was observed. In
      stark contrast, crystalline solids obtained by drying the solution revealed clear
      upconverted emission. Theoretical studies unveiled an underlying switching
      mechanism: the excited triplets in solution immediately decay back to the ground
      state through conformational twisting around a C?C bond and photoisomerization,
      whereas this deactivation path is effectively inhibited in the solid state. The
      finding of iPUC phenomena highlights the importance of controlling excited energy
      landscapes in condensed molecular systems. 

PMID- 25980804
TI  - The evolution of vasectomy reversal.
AB  - In the USA, about 500,000 vasectomies are performed each year, with up to 6% of
      men requesting reversal. The technique of vasectomy reversal has evolved from
      macrosurgical to the implementation of both microscopic and robotic technologies.
      The very earliest attempts at vasectomy reversal, the vasoepididymostomy and
      vasovasostomy, have remained central in the treatment of male infertility and
      will continue to be so for years to come. As seen throughout its history,
      urological microsurgery has consistently implemented advanced techniques and
      state-of-the art technology in its craft, and its continued refinement will allow
      for even more favorable outcomes in the lives of patients seeking restoration of
      fertility following vasectomy. Here, we review the evolution of vasectomy
      reversal and its current techniques.

PMID- 25980806
TI  - Utility of Stable Isotope and Cytochrome Oxidase I Gene Sequencing Analyses in
      Inferring Origin and Authentication of Hairtail Fish and Shrimp.
AB  - Mislabeling of fishery products continues to be a serious threat to the global
      market. Consequently, there is an urgent necessity to develop tools for
      authenticating and establishing their true origin. This investigation evaluates
      the suitability of stable isotopes and cytochrome oxidase I (COI) sequencing in
      identifying and tracing the origin of hairtail fish and shrimp. By use of COI
      sequencing, the hairtail fish samples were identified as Trichiurus japonicus and
      Trichiurus lepturus, while the shrimp samples were identified as Pandalus
      borealis, Marsupenaeus japonicus, Fenneropenaeus chinensis, Litopenaeus vannamei,
      Penaeus monodon, and Solenocera crassicornis. Linear discriminant analysis (LDA)
      of stable isotopes further categorized the individuals of the same species based
      on the country of origin. Natural and farmed shrimp (from the same country) were
      distinctly differentiated on the basis of stable isotope values. Therefore, these
      two methods could be cooperatively utilized to identify and authenticate fishery
      products, the utilization of which would enhance transparency and fair trade. 

PMID- 25980807
TI  - The physical foundation of FN = kh(3/2) for conical/pyramidal indentation loading
      curves.
AB  - A physical deduction of the FN = kh(3/2) relation (where FN is normal force, k
      penetration resistance, and h penetration depth) for conical/pyramidal
      indentation loading curves has been achieved on the basis of elementary
      mathematics. The indentation process couples the productions of volume and
      pressure to the displaced material that often partly plasticizes due to such
      pressure. As the pressure/plasticizing depends on the indenter volume, it follows
      that FN = FNp(1/3) . FNV(2/3), where the index p stands for pressure/plasticizing
      and V for indentation volume. FNp does not contribute to the penetration, only
      FNV. The exponent 2/3 on FNV shows that while FN is experimentally applied; only
      FN(2/3) is responsible for the penetration depth h. Thus, FN = kh(3/2) is deduced
      and the physical reason is the loss of FN(1/3) for the depth. Unfortunately, this
      has not been considered in teaching, textbooks, and the previous deduction of
      numerous common mechanical parameters, when the Love/Sneddon deductions of an
      exponent 2 on h were accepted and applied. The various unexpected experimental
      verifications and applications of the correct exponent 3/2 are mentioned and
      cited. Undue mechanical parameters require correction not only for safety
      reasons.

PMID- 25980808
TI  - Integrated genomics identifies convergence of ankylosing spondylitis with global
      immune mediated disease pathways.
AB  - Ankylosing spondylitis(AS), a highly heritable complex inflammatory arthritis.
      Although, a handful of non-HLA risk loci have been identified, capturing the
      unexplained genetic contribution to AS pathogenesis remains a challenge
      attributed to additive, pleiotropic and epistatic-interactions at the molecular
      level. Here, we developed multiple integrated genomic approaches to quantify
      molecular convergence of non-HLA loci with global immune mediated diseases. We
      show that non-HLA genes are significantly sensitive to deleterious mutation
      accumulation in the general population compared with tolerant genes. Human
      developmental proteomics (prenatal to adult) analysis revealed that proteins
      encoded by non-HLA AS risk loci are 2-fold more expressed in adult hematopoietic
      cells.Enrichment analysis revealed AS risk genes overlap with a significant
      number of immune related pathways (p < 0.0001 to 9.8 * 0(-12)). Protein-protein
      interaction analysis revealed non-shared AS risk genes are highly clustered seeds
      that significantly converge (empirical; p < 0.01 to 1.6 * 10(-4)) into networks
      of global immune mediated disease risk loci. We have also provided initial
      evidence for the involvement of STAT2/3 in AS pathogenesis. Collectively, these
      findings highlight molecular insight on non-HLA AS risk loci that are not
      exclusively connected with overlapping immune mediated diseases; rather a
      component of common pathophysiological pathways with other immune mediated
      diseases. This information will be pivotal to fully explain AS pathogenesis and
      identify new therapeutic targets.

PMID- 25980810
TI  - Dietary supplementation with glutamine and gamma-aminobutyric acid improves
      growth performance and serum parameters in 22- to 35-day-old broilers exposed to
      hot environment.
AB  - This study was designed using 360 21-day-old chicks to determine the influences
      of diet supplementation with glutamine (5 g/kg), gamma-aminobutyric acid (GABA,
      100 mg/kg) or their combinations on performance and serum parameters exposed to
      cycling high temperatures. From 22 to 35 days, the experimental groups (2 * 2)
      were subjected to circular heat stress by exposing them to 30-34  degrees C
      cycling, while the positive control group was exposed to 23  degrees C constant.
      The blood of broilers was collected to detect serum parameters on days 28 and 35.
      Compared with the positive control group, the cycling high temperature decreased
      (p < 0.05) the feed consumption, weight gain and serum total protein (TP),
      glucose, thyroxine (T4), insulin, alkaline phosphatase (ALP), glutamine, GABA and
      glutamate levels, while increased (p < 0.05) the serum triglyceride (TG),
      corticosterone (CS), glucagon (GN), creatine kinase (CK), glutamic oxaloacetic
      transaminase (GOT), nitric oxide synthase (NOS), glutamate pyruvate transaminase
      (GPT) and lactate dehydrogenase (LDH) levels during 22-35 days. However, dietary
      glutamine (5 g/kg) increased (p < 0.05) the feed consumption, weight gain and
      serum levels of glutamine, TP, insulin and ALP, but decreased (p < 0.05) the
      serum TG, CK, GOT, NOS and GPT levels. Diet supplemented with GABA also increased
      (p < 0.05) weight gain and the serum levels of TP, T4, ALP, GABA and glutamine.
      In addition, the significant interactions (p < 0.05) between glutamine and GABA
      were found in the feed consumption, weight gain and the serum ALP, CK, LDH, GABA,
      T3 and T4 levels of heat-stressed chickens. This research indicated that dietary
      glutamine and GABA improved the antistress ability in performance and serum
      parameters of broilers under hot environment. 

PMID- 25980811
TI  - Contact lens hygiene compliance and lens case contamination: A review.
AB  - A contaminated contact lens case can act as a reservoir for microorganisms that
      could potentially compromise contact lens wear and lead to sight threatening
      adverse events. The rate, level and profile of microbial contamination in lens
      cases, compliance and other risk factors associated with lens case contamination,
      and the challenges currently faced in this field are discussed. The rate of lens
      case contamination is commonly over 50%. Coagulase-negative Staphylococcus,
      Bacillus spp., Pseudomonas aeruginosa and Serratia marcescens are frequently
      recovered from lens cases. In addition, we provide suggestions regarding how to
      clean contact lens cases and improve lens wearers' compliance as well as future
      lens case design for reducing lens case contamination. This review highlights the
      challenges in reducing the level of microbial contamination which require an
      industry wide approach. 

PMID- 25980812
TI  - Hazard assessment through hybrid in vitro / in silico approach: The case of
      zearalenone.
AB  - Within the framework of reduction, refinement and replacement of animal
      experiments, new approaches for identification and characterization of chemical
      hazards have been developed. Grouping and read across has been promoted as a most
      promising alternative approach. It uses existing toxicological information on a
      group of chemicals to make predictions on the toxicity of uncharacterized ones.
      In the present work, the feasibility of applying in vitro and in silico
      techniques to group chemicals for read across was studied using the food
      mycotoxin zearalenone (ZEN) and metabolites as a case study. ZEN and its reduced
      metabolites are known to act through activation of the estrogen receptor alpha
      (ERalpha). The ranking of their estrogenic potencies appeared highly conserved
      across test systems including binding, in vitro and in vivo assays. This data
      suggests that activation of ERalpha may play a role in the molecular initiating
      event (MIE) and be predictive of adverse effects and provides the rationale to
      model receptor-binding for hazard identification. The investigation of receptor
      ligand interactions through docking simulation proved to accurately rank
      estrogenic potencies of ZEN and reduced metabolites, showing the suitability of
      the model to address estrogenic potency for this group of compounds. Therefore,
      the model was further applied to biologically uncharacterized, commercially
      unavailable, oxidized ZEN metabolites (6alpha-, 6beta-, 8alpha-, 8beta-, 13- and
      15-OH-ZEN). Except for 15-OH-ZEN, the data indicate that in general, the oxidized
      metabolites would be considered a lower estrogenic concern than ZEN and reduced
      metabolites.

PMID- 25980813
TI  - A Review on Mechanisms of Anti Tumor Activity of Chalcones.
AB  - Chalcones comprise a characteristic framework of 1, 3-diaryl-2-propen-1-one. They
      have been heralded as promising anti cancer drugs and have received much
      attention in the field of cancer research and drug development. The cytotoxicity
      of these potent pharmacophores is attributable to a wide spectrum of biological
      activities like anti inflammatory, anti proliferative, anti fungal, etc. These
      anti tumor activities are effectuated through apoptosis, cell cycle arrest, anti
      tubulin and so forth. This review summarizes the recent developments on anti
      tumor activity of synthetic and natural chalcones and their detailed underlying
      mechanisms as reported in the past. 

PMID- 25980814
TI  - Role of Rap2 and its Downstream Effectors in Tumorigenesis.
AB  - Rap2, a member of the GTP-binding proteins, is widely upregulated in many types
      of tumors. The specific effectors of Rap2 can affect multiple cancer-associated
      cellular processes, including cytoskeleton reorganization, proliferation,
      migration, and inflammation. However, the functional role of Rap2 in
      tumorigenesis and the interplay between different effectors remain to be fully
      elucidated. A more thorough understanding of the cancer-associated signaling
      networks of Rap2 is expected to facilitate drug discovery targeting Rap2 for
      cancer therapy. The present review mainly focused on recent studies on the
      functional and physical interactions between Rap2 and its effectors. We also
      speculated on the relevance of these pathways to tumorigenesis. 

PMID- 25980815
TI  - Immunotherapeutic Impact of Toll-like Receptor Agonists in Breast Cancer.
AB  - Onset of tumors in breast cancer is a multi-factorial event at different ages and
      ethnic populations. The conventional treatment strategy suggests use of anti
      estrogen drugs and selective estrogen receptor modulators (SERMs). Although, this
      strategy has achieved significant success to prevent tumor growth and metastasis
      and is still developing under an active field of research, the emergence of
      immunotherapy is a potential modern approach for breast cancer. In addition to
      SERMs, the screening of selective agonists for toll-like receptor (TLR) signals
      confers a new area of breast cancer therapy. Recent investigations also indicate
      significance of TLR signals in the regulation of tumor suppressor p53 gene
      expression. The TLR agonists have an ability to facilitate activation of natural
      killer cells, CD8 T cells, B cells, and alpha and beta interferons and induce
      cellular cytotoxicity. The ongoing developments in cancer research also suggested
      an approach for intra-tumoral generation of cellular cytotoxicity to induce
      apoptosis. Both of these events promote destruction of tumor cells in a localized
      manner and thus, having impact on immunotherapy. Keeping a cautious eye on the
      context, we propose the prospect of TLR signals in the development of therapy for
      breast cancer. 

PMID- 25980816
TI  - Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication.
AB  - ROS have vital roles in cellular signaling and homeostasis. At low concentration,
      ROS promotes cancer cell survival by the activation of growth factors and MAP
      kinases (MAPKs) that further activates cell cycle progression. At high
      concentration, ROS produces oxidative stress that activates programmed cell death
      or apoptosis. However, this fine distinction of ROS action either as a growth
      promoter or pro-apoptotic agent depends not only on dosage (concentration) but
      also on the duration, type, and site of ROS generation. The female steroid
      estrogens and their various metabolites generate ROS in the breast cancer cells.
      Slow, sustained and moderate level of ROS generated by estrogens and their
      metabolites cause initiation and progression of breast cancer. ROS generated by
      estrogens affect pro-proliferative (e.g. cyclin D1, Cdc2), prosurvival (e.g.
      AKT), antiapoptotic (e.g. BCl2) and pro-inflammatory (e.g. NF-kappaB) molecules.
      These multipronged actions of ROS lead to the activation of several signaling
      pathways involved in the breast cancer cell survival and proliferation, resulting
      in the progression of breast cancer. Present review article provides insights
      into the role of estrogen generated ROS and its associated signaling pathways in
      the initiation and progression of breast cancer. The importance of ROS as breast
      cancer drug target has also been discussed. 

PMID- 25980817
TI  - The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next
      Level with the First in Class Molecule EDO-S101.
AB  - Chemotherapy may still be an essential component to treat cancer in combination
      with new targeted therapies. But chemotherapy needs to get smarter in order to
      make those combination regimens more effective and also more tolerable,
      particularly for an aging population. We describe the first time the synthesis
      and pharmacological testing of a fusion molecule comprising of the alkylator
      bendamustine and the HDAC-inhibitor vorinostat. The drug was designed to allow
      for the exploitation of both mechanisms of action simultaneously with the goal to
      provide a molecule with superior efficacy over the single agents. The
      pharmacological testing confirms the full functional capacity of both moieties
      and encouraging pharmacological data raises the hope that the drug may turn out
      to be a great addition to the armentarium of anticancer agents. 

PMID- 25980818
TI  - SCYL1-BP1 affects cell cycle arrest in human hepatocellular carcinoma cells via
      Cyclin F and RRM2.
AB  - The cell cycle is regulated via important biological mechanisms. Controlled
      expression of cell cycle regulatory proteins is crucial to maintain cell cycle
      progression. However, unbalanced protein expression leads to many diseases, such
      as cancer. Previous research suggests that SCYL1-BP1 function might be related to
      cell cycle progression and SCYL1-BP1 dysfunction to diseases through undefined
      mechanisms. In this research, an unbiased yeast two-hybrid screen was used to
      find protein(s) with potential biological relevance to SCYL1-BP1 function, and a
      novel interaction was recognized between SCYL1-BP1 and Cyclin F. This interaction
      was chosen as a paradigm to study SCYL1-BP1 function in cell cycle progression
      and its possible role in tumorigenesis. We found that SCYL1-BP1 binds to Cyclin F
      both in vivo and in vitro. SCYL1-BP1 overexpression promoted expression of the
      CCNF gene and simultaneously delayed Cyclin F protein degradation. SCYL1-BP1
      knockdown reduced the expression of endogenous Cyclin F. It was also demonstrated
      in functional assays that SCYL1-BP1 overexpression induces G2/M arrest in
      cultured liver cells. Furthermore, SCYL1-BP1 sustained RRM2 protein expression by
      reducing its ubiquitination. Thus, we propose that SCYL1- BP1 affects the cell
      cycle through increasing steady state levels of Cyclin F and RRM2 proteins, thus
      constituting a dual regulatory circuit. This study provides a possible mechanism
      for SCYL1-BP1-mediated cell cycle regulation and related diseases. 

PMID- 25980819
TI  - Recent developments in carbon nanomaterial sensors.
AB  - Carbon nanomaterials are among the most broadly discussed, researched and applied
      of synthetic nanomaterials. The structural diversity of these materials provides
      an array of unique electronic, magnetic and optical properties, which when
      combined with their robust chemistry and ease of manipulation, makes them
      attractive candidates for sensor applications. Furthermore, the biocompatibility
      exhibited by many carbon nanomaterials has seen them used as in vivo biosensors.
      Carbon nanotubes, graphene and carbon dots have come under intense scrutiny, as
      either discrete molecular-like sensors, or as components which can be integrated
      into devices. In this review we consider recent developments in the use of carbon
      nanoparticles and nanostructures as sensors and consider how they can be used to
      detect a diverse range of analytes. 

PMID- 25980820
TI  - Radiotherapy combined with immune checkpoint blockade immunotherapy: Achievements
      and challenges.
AB  - To date, several kinds of immunomodulating monoclonal antibodies (mAbs) have been
      applied in clinical trials, such as anti-cytotoxic T-lymphocyte antigen-4 (anti
      CTLA-4) mAb and anti-programmed death-1 (anti-PD-1) mAb. With the recent success
      of cancer immunotherapy, especially the checkpoint inhibitors, the renewed
      interest in immunotherapy as a treatment modality has gained extensive attention.
      The irradiated tumor cell death can enhance antitumor immunity by inducing
      antigen expression on tumor cells and activating lymphocytes. Radiotherapy (RT)
      combined with immunotherapy has revealed promising outcomes in various animal
      models. However, this new paradigm is often considered as a medical spectacle
      without a unifying model, and its mechanisms have yet to be elucidated. The
      purpose of this review is to investigate previously published studies of
      radiotherapy combined with checkpoint blockades by the following aspects:
      exploring the potential mechanisms; identifying the most beneficial dose,
      fraction and target site for RT; finding an appropriate time window to combine
      these two treatments; and discussing the toxicity and suitable treatment
      evaluating criteria. 

PMID- 25980821
TI  - Dental treatment needs and health care-seeking behaviours of patients with acute
      odontogenic infections in Lithuania.
AB  - AIMS: To assess patients with acute odontogenic maxillofacial infections (AOMIs),
      regarding their functional dentition and dental treatment needs, and identify
      factors explaining these outcomes. METHODS: During a 1-year period, 160 patients
      with AOMIs were treated at the specialised dental care centre of Vilnius
      University. Both oral status and specific dental treatment needs were evaluated
      for each patient. For the restorative dental treatment need, we examined if
      patients needed fillings, crowns or bridges. Periodontal dental treatment needs
      were based only on the most severe cases, and patients were allocated either to a
      group for which periodontal treatment was recommended or to a group that did not
      need periodontal treatment. Based on these clinical assessments, four ratios for
      specific dental treatment needs (restorations, extractions, endodontic treatment
      and periodontal treatment) and two summative ratios (total dental treatment needs
      and presence of a functional dentition) were calculated. The questionnaire
      included variables from various domains. RESULTS: Patients with AOMIs retained
      one-third of their functional dentition and the mean +/- standard deviation of
      their total dental treatment needs was 46.0 +/- 29.7%, of which 32.4 +/- 17.1%
      related to the need for restorations. Higher dental treatment needs were
      associated with a low level of education, low income, irregular oral self-care,
      systemic diseases and self-treatment of acute dental conditions before seeking
      professional help. CONCLUSIONS: Patients with AOMIs retained one-third of their
      functional dentition, and almost half of their dentition were in need of dental
      treatment.

PMID- 25980823
TI  - Glabridin inhibits cancer stem cell-like properties of human breast cancer cells:
      An epigenetic regulation of miR-148a/SMAd2 signaling.
AB  - In breast cancer, the cancer stem cells (CSCs) are thought to be the main cause
      of metastasis and recurrence. Targeting of CSCs or cancer cells with stem cell
      like properties has become a new approach for the treatment of breast cancer.
      Glabridin (GLA), a phytochemical from the root of Glycyrrhiza glabra, exhibited
      effective antitumor properties in various human cancer cells. However, the roles
      of GLA in the regulation of CSC-like properties and the underlying molecular
      mechanisms remain unclear. Here, we reported that GLA attenuated the CSC-like
      properties through microRNA-148a (miR-148a)/transforming growth factor beta
      (TGFbeta)-SMAD2 signal pathway in vitro and in vivo. In MDA-MB-231 and Hs-578T
      breast cancer cell lines, GLA enhanced the expression of miR-148a through DNA
      demethylation. By targeting of the SMAD2-3'-UTR, miR-148a blocked the
      expression/activation of SMAD2, and in turn, restored the epithelial
      characteristics, adhesive abilities, and CSC-like properties. Furthermore, in
      mouse xenograft models, we also confirmed that GLA attenuated the tumor growth,
      mesenchymal characteristics, and CSCs-like properties via demethylation-activated
      miR-148a. Our findings suggested a potential treatment strategy to reduce the
      CSCs-like properties, and therefore enhance the effectiveness of breast cancer
      therapy.

PMID- 25980822
TI  - Functional lumen imaging of the gastrointestinal tract.
AB  - This nonsystematic review aims to describe recent developments in the use of
      functional lumen imaging in the gastrointestinal tract stimulated by the
      introduction of the functional lumen imaging probe. When ingested food in liquid
      and solid form is transported along the gastrointestinal tract, sphincters
      provide an important role in the flow and control of these contents. Inadequate
      function of sphincters is the basis of many gastrointestinal diseases. Despite
      this, traditional methods of sphincter diagnosis and measurement such as
      fluoroscopy, manometry, and the barostat are limited in what they can tell us. It
      has long been thought that measurement of sphincter function through resistance
      to distension is a better approach, now more commonly known as distensibility
      testing. The functional lumen imaging probe is the first medical measurement
      device that purports in a practical way to provide geometric profiling and
      measurement of distensibility in sphincters. With use of impedance planimetry, an
      axial series of cross-sectional areas and pressure in a catheter-mounted
      allantoid bag are used for the calculation of distensibility parameters. The
      technique has been trialed in many valvular areas of the gastrointestinal tract,
      including the upper esophageal sphincter, the esophagogastric junction, and the
      anorectal region. It has shown potential in the biomechanical assessment of
      sphincter function and characterization of swallowing disorders, gastroesophageal
      reflux disease, eosinophilic esophagitis, achalasia, and fecal incontinence. From
      this early work, the functional lumen imaging technique has the potential to
      contribute to a better and more physiological understanding of narrowing regions
      in the gastrointestinal tract in general and sphincters in particular. 

PMID- 25980824
TI  - Surgical Trainers' Experience and Perspectives on Workplace-Based Assessments.
AB  - BACKGROUND: Workplace-based assessments (WBAs) were designed to provide formative
      feedback to trainees throughout their surgical career. Several studies highlight
      dissatisfaction with WBAs, and some feel they lack validity and reliability and
      exist as a "tick-box exercise." No studies have looked at the attitudes of the
      assessor. AIM: The aim of this study was to evaluate perceptions and experience
      of the 4 intercollegiate surgical curriculum programme WBAs by assessors.
      METHODS: An 18-item electronic questionnaire, including 6-point Likert scoring
      questions, was e-mailed to all surgical program directors for distribution to
      general surgery trainers within their deanery. RESULTS: In total, 64 responses
      were received. All trainers had been trained in using WBAs. Trainers had the most
      experience with procedure-based assessments (PBAs)-72% of trainers had completed
      more than 25 PBAs. Trainers felt PBAs were the most beneficial WBA, and both PBAs
      and case-based discussions were regarded as significantly more useful than mini
      clinical evaluation exercise (p < 0.05). More than 74% stated that WBAs were
      mainly initiated by trainees, and only 10% had specific sessions allocated to
      complete WBAs. CONCLUSION: WBAs are regarded as beneficial to trainees. The
      results suggest that assessors feel case-based discussions and PBAs, which assess
      higher thinking and practice of complex practical skills, respectively, are
      significantly more useful than assessments involved in observing more
      straightforward clinical and procedural interactions.

PMID- 25980825
TI  - The Effect of Afternoon Operative Sessions of Laparoscopic Cholecystectomy
      Performed by Senior Surgeons on the General Surgery Residency Program: A
      Comparative Study.
AB  - OBJECTIVE: Laparoscopic cholecystectomy (LC) has been the gold standard for
      surgical treatment of gallbladder disease since 1980. This laparoscopic surgical
      procedure is one of the first to be performed by general surgery residents. There
      is a learning curve required to excel at performing LC. During this period, the
      operation needs to be performed under the supervision of a senior surgeon. The
      purpose of this study was to compare LC performed by residents with that
      performed by senior surgeons using the following parameters: operative time,
      conversion rate, complication rate, and mean length of hospital stay. METHODS:
      This retrospective study included 1219 patients who underwent elective LC in our
      institute-788 operated on by a senior surgeon and 431 by a resident. RESULTS: The
      mean operative time was 39 +/- 19 minutes. There was a significant difference
      between the groups, as the mean operative time for the resident group was 49.9 +/
      13 compared with 33.7 +/- 6 for the senior surgeon group. The overall conversion
      rate was 2.1%, the complication rate was 2.2%, and the mean length of hospital
      stay was 1.5 days. There were no statistically significant differences between
      the groups for these parameters. CONCLUSIONS: The only significant difference
      between the groups was a longer operative time, as the conversion rate,
      complication rate, and mean length of stay were the same. Therefore, it is safe
      for LC to be performed by residents supervised by a senior surgeon.

PMID- 25980826
TI  - Accreditation Council for Graduate Medical Education Compliance and Resident
      Competence in Hepatopancreaticobiliary Surgery during General Surgery Residency:
      A Program Director Review.
AB  - OBJECTIVE: A survey of general surgery (GS) program directors (PD) was performed
      to determine how Accreditation Council for Graduate Medical Education (ACGME)
      hepatopancreatobiliary (HPB) requirements are met and compare the findings with
      previous national averages. The objectives were to establish whether GS
      residencies are in compliance with ACGME recommendations. Secondary objectives
      aimed to determine if fellowship affects residency training. METHODS: A 30
      question survey was sent out to GS PDs registered with Association of Program
      Directors in Surgery. Analysis of the responses was then completed using
      statistical software (GraphPad) and compared with the ACGME data. RESULTS:
      Although HPB training and exposure has changed, most programs continue to meet
      HPB requirements at their main institution (73%). Overall, 27% of PDs now send
      residents to outside facilities or have hired new HPB faculty to manage the shift
      in caseload. GS graduates have HPB numbers comparable to the national resident
      averages of 2010 to 2011, and many programs graduate residents exceeding ACGME
      HPB requirements. Although 69% of residents complete >50% of HPB cases, only 50%
      of PDs felt residents were competent. Altogether, 30% of programs had HPB
      fellowships; few PDs felt fellows positively affected residency training.
      CONCLUSIONS: PDs feel that residents achieve more than minimum required HPB
      numbers required by the ACGME but not all are competent. Fellows reduce resident
      exposure to HPB cases. More simulation and autonomy may improve HPB education in
      GS residency.

PMID- 25980827
TI  - The Face, Content, and Construct Validity Assessment of a Focused Assessment in
      Sonography for Trauma Simulator.
AB  - OBJECTIVE: Hemorrhage identification in trauma care is a major priority. Focused
      assessment in sonography for trauma (FAST) offers a rapid, reliable means of
      detecting torso bleeding. The aims of this study were to conduct a face, content,
      and construct validity assessment of a FAST simulator and establish a rigorous
      assessment tool. DESIGN: Participants were requested to perform a FAST scan and
      state if any abnormality was found in each region. Metrics evaluated included
      time, errors, and missed targets. Accuracy of images obtained was assessed by 2
      independent radiologists. Experts completed a face and content validity
      questionnaire at the end of the study. SETTING: The study took place in the
      simulation suite within the Academic Surgical Unit of the Department of Surgery
      and Cancer. PARTICIPANTS: Novices had no prior experience with ultrasound,
      intermediates had less than 6 months experience with fewer than 50 FAST scans
      performed, and experts had more than 1 year of experience with greater than 100
      FAST scans performed. There were 31 participants: 11 experts, 10 intermediates,
      and 10 novices. RESULTS: The face and content validity questionnaire scored high
      marks across all categories and achieved an overall median realism score of 8 +/-
      1.5 on a Likert scale. Experts performed the FAST scan faster with more accuracy
      and fewer errors than other cohorts (p < 0.001). Both the novices and
      intermediates were the slowest, least accurate, and either missed or made the
      most errors when scanning the lung bases and spleen. CONCLUSIONS: This study has
      established the face, content, and construct validities of a FAST simulator,
      which could be used to accelerate training for novices. Additionally, it has
      demonstrated a rigorous method for FAST assessment, which has proven to be
      effective and in doing so addressed some of the criticisms leveled against it.

PMID- 25980828
TI  - The Relationship Between Technical And Nontechnical Skills Within A Simulation
      Based Ureteroscopy Training Environment.
AB  - OBJECTIVE: Little integration of technical and nontechnical skills (e.g.,
      situational awareness, communication, decision making, teamwork, and leadership)
      teaching exists within surgery. We therefore aimed to (1) evaluate the
      relationship between these 2 skill sets within a simulation-based environment and
      (2) assess if certain nontechnical skill components are of particular relevance
      to technical performance. DESIGN: A prospective analysis of data acquired from a
      comparative study of simulation vs nonsimulation training was conducted. Half of
      the participants underwent training of technical and nontechnical skills within
      ureteroscopy, with the remaining half undergoing no training. All were assessed
      within a full immersion environment against both technical (time to completion,
      Objective Structured Assessment of Technical Skills, and task-specific checklist
      scores) and nontechnical parameters (Nontechnical Skills for Surgeons [NOTSS]
      rating scale). The data of whole and individual cohorts were analyzed using
      Pearson correlation coefficient. SETTING: The trial took place within the
      Simulation and Interactive Learning Centre at Guy's Hospital, London, UK.
      PARTICIPANTS: In total, 32 novice participants with no prior practical
      ureteroscopy experience were included within the data analysis. RESULTS: A
      correlation was found within all outcome measures analyzed. For the whole cohort,
      a strong negative correlation was found between time to completion and NOTSS
      scores (r = -0.75, p < 0.001), with strong positive correlations identified when
      NOTSS scores were compared with Objective Structured Assessment of Technical
      Skills (r = 0.89, p < 0.001) and task-specific checklist scores (r = 0.91, p <
      0.001). Similar results were observed when each cohort was analyzed separately.
      Finally, all individual nontechnical skill components demonstrated a strong
      correlation with all technical skill parameters, regardless of training.
      CONCLUSIONS: A strong correlation between technical and nontechnical performance
      exists, which was demonstrated to be irrespective of training received. This may
      suggest an inherent link between skill sets. Furthermore, all nontechnical skill
      sets are important in technical performance. This supports the notion that both
      of these skills should be trained and assessed together within 1 curriculum.

PMID- 25980829
TI  - Ranking Surgical Residency Programs: Reputation Survey or Outcomes Measures?
AB  - OBJECTIVE: The release of general surgery residency program rankings by Doximity
      and U.S. News & World Report accentuates the need to define and establish
      measurable standards of program quality. This study evaluated the extent to which
      program rankings based solely on peer nominations correlated with familiar
      program outcomes measures. DESIGN: Publicly available data were collected for all
      254 general surgery residency programs. To generate a rudimentary outcomes-based
      program ranking, surgery programs were rank-ordered according to an average
      percentile rank that was calculated using board pass rates and the prevalence of
      alumni publications. A Kendall tau-b rank correlation computed the linear
      association between program rankings based on reputation alone and those derived
      from outcomes measures to validate whether reputation was a reasonable surrogate
      for globally judging program quality. RESULTS: For the 218 programs with complete
      data eligible for analysis, the mean board pass rate was 72% with a standard
      deviation of 14%. A total of 60 programs were placed in the 75th percentile or
      above for the number of publications authored by program alumni. The
      correlational analysis reported a significant correlation of 0.428, indicating
      only a moderate association between programs ranked by outcomes measures and
      those ranked according to reputation. Seventeen programs that were ranked in the
      top 30 according to reputation were also ranked in the top 30 based on outcomes
      measures. CONCLUSIONS: This study suggests that reputation alone does not fully
      capture a representative snapshot of a program's quality. Rather, the use of
      multiple quantifiable indicators and attributes unique to programs ought to be
      given more consideration when assigning ranks to denote program quality. It is
      advised that the interpretation and subsequent use of program rankings be met
      with caution until further studies can rigorously demonstrate best practices for
      awarding program standings.

PMID- 25980830
TI  - A Descriptive Analysis of the Use of Workplace-Based Assessments in UK Surgical
      Training.
AB  - BACKGROUND: Workplace-based assessments (WBAs) were introduced formally in the UK
      in 2007. The aim of the study was to describe the use of WBAs by UK surgical
      trainees and examine variations by training region, specialty, and level of
      training. METHODS: The database of the Intercollegiate Surgical Curriculum
      Programme was examined for WBAs between August 2007 and July 2013, with in-depth
      analysis of 2 periods: August 2011 to July 2012 and August 2012 to July 2013.
      RESULTS: The numbers of validated WBAs per trainee per year increased more than 7
      fold, from median 6 per trainee in 2007 to 2008, to 39 in 2011 to 2012, and 44 in
      2012 to 2013. In the period 2011 to 2012, 58.4% of core trainees completed the
      recommended 40 WBAs, with only 38.1% of specialty trainees achieving 40 validated
      WBAs. In the period 2012 to 2013, these proportions increased to 67.7% and 57.0%
      for core and specialty trainees, respectively. Core trainees completed more WBAs
      per year than specialty trainees in the same training region. London core
      trainees completed the highest numbers of WBAs in both the periods 2011 to 2012
      (median 67) and 2012 to 2013 (median 74). There was a peak in WBAs completed by
      London specialty trainees in the period 2012 to 2013 (median 63). The most
      validated WBAs were completed by ST1/CT1 (specialty surgical training year, core
      surgical training year), with a gradual decrease in median WBAs to ST4, followed
      by a plateau; in the period 2012 to 2013, there was an increase in WBAs at ST8.
      Core surgical trainees complete ~50% "operative" (procedure-based
      assessment/direct observation of procedural skills) and ~50% "nonoperative"
      assessments (case-based discussion/clinical evaluation exercise). During
      specialty training, procedure-based assessments represented ~46% of WBAs, direct
      observation of procedural skills 11.2%, case-based discussion ~23%, and clinical
      evaluation exercise ~15%. CONCLUSIONS: UK surgical trainees are, on an average,
      undertaking 1 WBA per week. Variation exists in use of WBAs between training
      regions. Core trainees tend to use the spectrum of WBAs more frequently than
      their senior colleagues do. Further work is required to examine the role of WBAs
      in assessment, and engagement and training of trainers in processes and
      validation of WBAs.

PMID- 25980831
TI  - Participatory appraisal of the impact of epizootic lymphangitis in Ethiopia.
AB  - Epizootic lymphangitis (EZL) is reported to have a significant impact upon
      livelihoods within resource-poor settings. This study used a participatory
      approach to explore peoples' experiences of EZL and examine the perceived impact
      of disease, owner knowledge and understanding of EZL, lay management of disease
      and, attitudes and strategies towards disease prevention. Focus-group discussions
      were held with 358 cart-horse owners and drivers recruited from 7 towns attended
      by SPANA (Society for the protection of animals abroad) mobile veterinary clinics
      and 2 unexposed towns where no SPANA clinics were available. Focus group
      discussions explored four main research questions: (1) Is EZL recognised by
      animal owners, and is this considered an important disease in equids? (2) What
      factors do animal owners associate with the development of disease? (3) What
      happens to an animal with clinical disease and how does this impact upon the
      owner/community? (4) Are measures taken to reduce disease occurrence? These key
      areas were explored using photographs, disease ranking, matrices and open
      discussion. Data were analysed using descriptive statistics and thematic
      analysis. The results are presented thematically and include: recognition and
      descriptions of EZL, treatment strategies used, disease priorities and ranking,
      impact of disease, disease transmission and attitudes and approaches to disease
      prevention. EZL was widely recognised and ranked highly as an important disease
      of equids. However, there was uncertainty around identifying early cases of EZL,
      and this could impact upon the timing of initiating treatment and separating
      potentially infectious animals. People had varying knowledge of effective methods
      for disease prevention and reported particular difficulties with isolating
      infected animals. The impact of EZL was multi-dimensional and encompassed effects
      upon the horse, the individual owner and the wider society. Working equids
      provide a vital utility and source of income to many people in resource-poor
      settings. Often, infection with EZL resulted in a reduction in working ability
      which had a direct impact upon the livelihoods of owners and their dependent
      family members. EZL also impacted upon the welfare of the horse as sick animals
      continued to be worked and, in advanced cases, horses were abandoned due to
      ineffective or unavailable treatment. This study conceptualises the importance of
      EZL due to the effects of the disease on the horse and its impact upon human
      livelihoods. Epizootic lymphangitis is a neglected disease that requires further
      investigation in order to develop practical and sustainable disease control
      strategies within endemic regions. 

PMID- 25980832
TI  - Savagea faecisuis gen. nov., sp. nov., a tylosin- and tetracycline-resistant
      bacterium isolated from a swine-manure storage pit.
AB  - A polyphasic taxonomic study using morphological, biochemical, chemotaxonomic and
      molecular methods was performed on three strains of a Gram-stain positive, non
      sporeforming, motile aerobic rod-shaped bacterium resistant to tylosin and
      tetracycline isolated from a swine-manure storage pit. On the basis of 16S rRNA
      gene sequence analyses, it was confirmed that these isolates are highly related
      to each other and form a hitherto unknown lineage within the Planococcaceae. In
      particular, pairwise analysis of the 16S rRNA gene sequence demonstrated that the
      novel organism is closely related to members of the genus Sporosarcina (92.8-94.5
      %), Pyschrobacillus (93.5-93.9 %) and Paenisporosarcina (93.3-94.5 %). The
      predominant fatty acids were found to consist of iso-C15:0 and iso-C17:1 omega10c
      and the G+C mol% was determined to be 41.8. Based on biochemical, chemotaxonomic,
      and phylogenetic evidence, it is proposed that these novel strains be classified
      as a novel genus and species, Savagea faecisuis gen nov., sp. nov. The type
      strain is Con12(T) (=CCUG 63563(T) = NRRL B-59945(T) = NBRC 109956(T)).

PMID- 25980833
TI  - Inflammasomes-dependent regulation of IL-1beta secretion induced by the virulent
      Mycobacterium bovis Beijing strain in THP-1 macrophages.
AB  - Mycobacterium bovis is the causative agent of tuberculosis in cattle. Infection
      of macrophages with M. bovis leads to the activation of the "nucleotide binding
      and oligomerization, leucine-rich repeat and pyrin domains-containing protein 3"
      (NLRP3) and "absent in melanoma 2" (AIM2) inflammasomes, which in turn triggers
      release of the proinflammatory cytokine interleukin-1beta (IL-1beta) that
      contributes to bacterial clearance and plays a crucial role in the host defense.
      However, NLRP3 and AIM2 inflammasome activation is influenced by several factors
      and how IL-1beta secretion by M. bovis-infected macrophages is regulated via the
      inflammasome pathway remains unclear. Here we found that IL-1beta secretion and
      pro-IL-1beta protein accumulation were inhibited in THP-1 macrophages upon
      exposure to the virulent M. bovis Beijing strain in the presence of high K(+)
      concentrations, cycloheximide (a protein synthesis inhibitor) and PR-619 (a
      deubiquitinating enzyme inhibitor). Scavenging reactive oxygen species (ROS)
      induced by N-acetylcysteine reduced IL-1beta release independent of the
      mitochondrial permeability transition. Collectively, our results suggest that IL
      1beta secretion by M. bovis-infected THP-1 macrophages is reduced by high
      extracellular K(+) concentration, inhibition of new protein synthesis,
      deubiquitination, and ROS generation. 

PMID- 25980834
TI  - Ethanol production from Jerusalem artichoke tubers at high temperature by newly
      isolated thermotolerant inulin-utilizing yeast Kluyveromyces marxianus using
      consolidated bioprocessing.
AB  - Thermotolerant inulin-utilizing yeast strains were successfully isolated in this
      study. Among the isolated strains, Kluyveromyces marxianus DBKKU Y-102 was found
      to be the most effective strain for direct ethanol fermentation at high
      temperature from fresh Jerusalem artichoke (JA) tubers without inulin hydrolysis
      under consolidated bioprocessing (CBP). The maximum ethanol concentrations
      produced by this strain under the optimum culture conditions were 104.83 and
      97.46 g L(-1) at 37 and 40  degrees C, respectively. Data from this study clearly
      demonstrated that the use of thermotolerant inulin-utilizing yeast K. marxianus
      for ethanol production from fresh JA tubers in the CBP process not only provided
      high levels of ethanol, but also could eliminate the addition of external enzyme
      for inulin hydrolysis, which might lead to the reduction of operating costs. The
      expression of genes involved in carbohydrate metabolism in K. marxianus DBKKU Y
      102 during ethanol fermentation was investigated by real-time RT-PCR, and the
      results revealed that expression levels were distinctive depending on the growth
      phase and growth conditions. However, among the genes tested, adh4 and tdh2 were
      highly expressed under high temperature conditions in both exponential- and
      stationary-growth phases, suggesting that these genes might play a crucial role
      in acquiring thermotolerance ability in this organism under stress conditions.

PMID- 25980835
TI  - Mesorhizobium soli sp. nov., a novel species isolated from the rhizosphere of
      Robinia pseudoacacia L. in South Korea by using a modified culture method.
AB  - Strain NHI-8(T) was isolated from a forest soil sample, collected in South Korea,
      by using a modified culture method. Comparative analysis of its nearly full
      length 16S rRNA gene sequence showed that strain NHI-8(T) belongs to the genus
      Mesorhizobium and to be closely related to Mesorhizobium chacoense PR5(T) (97.32
      %). The levels of DNA-DNA relatedness between strain NHI-8(T) and reference type
      strains of the genus Mesorhizobium were 32.28-53.65 %. SDS-PAGE of total soluble
      proteins and the sequences of the housekeeping genes recA, glnII, and atpD were
      also used to support the clade grouping in rhizobia. The new strain contained
      summed feature 8 (57.0 %), cyclo-C19:0omega8c (17.3 %), and C18:0 (11.0 %) as the
      major fatty acids, as in genus Mesorhizobium. The strain contained cardiolipin,
      phosphatidylglycerol, ornithine-containing lipid, phosphatidylethanolamine,
      phosphatidyl-N-dimethylethanolamine, and phosphatidylcholine. Morphological and
      physiological analyses were performed to compare the characteristics of our
      strain with those of the reference type strains. Based on the results, strain NHI
      8(T) was determined to represent a novel member of the genus Mesorhizobium, and
      the name Mesorhizobium soli is proposed. The type strain is NHI-8(T) (=KEMB 9005
      153(T) = KACC 17916(T) = JCM 19897(T)).

PMID- 25980836
TI  - Reduced survival in microscopic polyangiitis patients with pulmonary fibrosis in
      a respiratory referral centre.

PMID- 25980837
TI  - Occasional presence of herpes viruses in synovial fluid and blood from patients
      with rheumatoid arthritis and axial spondyloarthritis.
AB  - Viral agents have been suspected as participants of immune-mediated disorders. In
      the case of rheumatic diseases, the synovial joint cavity represents a secluded
      area of inflammation which could harbor etiological agents. We analyzed by
      polymerase chain reaction the possible presence of DNA from various herpes
      viruses in blood and synovial fluid from patients with either rheumatoid
      arthritis (n = 18), axial spondyloarthritis (n = 11), or osteoarthritis (n = 8).
      Relevant findings were as follows: DNA from varicella zoster virus was found in
      synovial fluid but not in blood mononuclear cells from 33 % of patients with
      rheumatoid arthritis and in 45 % of patients with axial spondyloarthritis but not
      in patients with osteoarthritis. Also, DNA from herpes simplex viruses 1 and 2
      was found both in the blood and in the synovial fluid from 33 % of patients with
      rheumatoid arthritis. Our results indicate the occasional presence of DNA from
      herpes viruses in patients with rheumatoid arthritis or with axial
      spondyloarthritis. However, these findings might represent a parallel
      epiphenomenon of viral activation associated either with immunosuppressive
      therapy or with primary immune disturbances, rather than the etiological
      participation of herpes viruses in these disorders. 

PMID- 25980838
TI  - Limited sampling strategy for prolonged-release tacrolimus in renal transplant
      patients by use of the dried blood spot technique.
AB  - PURPOSE: The aim of this study was to develop a clinically applicable limited
      sampling strategy for ambulatory Caucasian kidney transplant patients to estimate
      area under the curve in a 24-h period (AUC0-24) of prolonged-release tacrolimus.
      METHODS: Twenty six kidney recipients, at least 6 months after transplantation,
      receiving prolonged-release tacrolimus, were enrolled. In each patient, seven
      blood samples were collected during a period of 24 h by use of the validated
      dried blood spot method. Best subset selection multiple linear regression was
      performed to derive limited sampling strategy (LSS). The equations were
      constrained to include a maximum of three samples collected within 4 h after the
      intake to maintain clinical applicability. To assess the predictive performance
      of LSS, residuals for each patient were calculated based on models fitted to a
      dataset where that patient was omitted. RESULTS: The prediction formula for the
      AUC(0-24) using the time points 0, 2, and 4 h after ingestion (C(0h)-C(2h)-C(4h))
      provided the highest correlation with the AUC(0-24) (r(2) = 0.95): AUC0-24 = 44.9
      + 8.9 * C(0h) + 2.1 * C(2h) + 7.6 * C(4h). Measures for bias and precision, i.e.,
      median percentage prediction error (MPPE) and median absolute prediction error
      (MAPE), were 0.4 and 4.8%, respectively. For the same patients, the correlation
      between C(24h) and AUC0-24 was worse (r(2) = 0.77) while MPPE and MAPE were 6.2
      and 7.2%, respectively. CONCLUSION: In the outpatient department, a LSS using
      C(0h)-C(2h)-C(4h) can be used for reliable estimation of the AUC(0-24) of
      prolonged-release tacrolimus.

PMID- 25980839
TI  - How to define nativeness in vagile organisms: lessons from the cosmopolitan moss
      Bryum argenteum on the island of Tenerife (Canary Islands).
AB  - The distinction between native and introduced biotas presents unique challenges
      that culminate in organisms with high long-distance dispersal capacities in a
      rapidly changing world. Bryophytes, in particular, exhibit large distribution
      ranges, and some species can truly be qualified as cosmopolitan. Cosmopolitan
      species, however, typically occur in disturbed environments, raising the question
      of their nativeness throughout their range. Here, we employ genetic data to
      address the question of the origin of the cosmopolitan, weedy moss Bryum
      argenteum on the island of Tenerife. The genetic diversity of B. argenteum on
      Tenerife was comparable to that found in continental areas due to recurrent
      colonisation events, erasing any signature of a bottleneck that would be expected
      in the case of a recent colonisation event. The molecular dating analyses
      indicated that the first colonisation of the island took place more than 100,000
      years ago, i.e. well before the first human settlements. Furthermore, the
      significant signal for isolation-by-distance found in B. argenteum within
      Tenerife points to the substantial role of genetic drift in establishing the
      observed patterns of genetic variation. Together, the results support the
      hypothesis that B. argenteum is native on Tenerife; although the existence of
      haplotypes shared between Tenerife and continental areas suggests that more
      recent, potentially man-mediated introduction also took place. While defining
      nativeness in organisms that are not deliberately introduced, and wherein the
      fossil record is extremely scarce, is an exceedingly challenging task, our
      results suggest that population genetic analyses can represent a useful tool to
      help distinguish native from alien populations.

PMID- 25980840
TI  - Comparative Respiratory Pathogenicity and Dynamic Tissue Distribution of Chinese
      Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and its
      Attenuated Strain in Piglets.
AB  - The outbreak of highly pathogenic porcine reproductive and respiratory syndrome
      (HP-PRRS) in 2006 devastated the Chinese swine industry. HP-PRRS virus is still
      the predominant strain in mainland China, rather than the classical PRRSV strain,
      and the attenuated live vaccine remains the preferred choice for protecting
      piglets against HP-PRRSV infection. To fully evaluate the safety of strain
      GDr180, the 180th attenuated virus of the HP-PRRSV strain GD, we used
      clinicopathological, microscopical, ultrastructural, serological and molecular
      biological methods to assess the different clinical manifestations and
      respiratory characteristics of piglets inoculated with HP-PRRSV strain GD or
      strain GDr180. The 5-week-old piglets inoculated with strain GD displayed marked
      clinical signs, including fever, anorexia, dyspnoea and tachypnoea. Significant
      interstitial pneumonia was present, characterized by thickened alveolar septa
      infiltrated with mononuclear cells and cell debris. However, the piglets
      inoculated with strain GDr180 and the negative control piglets showed neither
      clinical signs nor microscopical or ultrastructural lesions. Ultrastructural
      observation of the piglets' tracheas and examination of the dynamic tissue
      distributions of PRRSV strain GD and attenuated strain GDr180, by
      immunohistochemistry and fluorescence quantitative reverse transcription
      polymerase chain reaction, confirmed significant differences in their
      pathogenicity and distribution in the respiratory systems of piglets. The
      differences in pathogenicity are attributable to the different severity of the
      pathological changes in the pigs inoculated with the two strains. Thus, the HP
      PRRSV GDr180 strain is practically harmless to the respiratory systems of piglets
      and may be a safe candidate for inducing immunity against HP-PRRS. 

PMID- 25980841
TI  - Prevalence of Bartonella spp. in Canine Cutaneous Histiocytoma.
AB  - Canine cutaneous histiocytoma (CCH) is a common, benign neoplastic proliferation
      of histiocytes of Langerhans cell origin that often ulcerate, become secondarily
      infected and regress spontaneously. Bartonella is a fastidious genus of
      facultative intracellular pathogens that can be transmitted through arthropod
      bites and epidermal animal scratches and has been identified previously in the
      cytoplasm of histiocytes within granulomatous lesions and in skin biopsy samples
      of inflammatory pustules and papules. Based on the established inflammatory and
      oncogenic properties of Bartonella, we hypothesized that Bartonella spp. DNA
      could be amplified from CCH more often than from non-lesional skin and bacteria
      could be localized within skin tumours using indirect immunofluorescence (IIF).
      Paraffin wax-embedded surgical biopsy samples from dogs with CCH and non
      neoplastic skin adjacent to osteosarcomas (control group selected due to wide
      surgical margins) were retrieved from the archive of the pathology service of
      North Carolina State University College of Veterinary Medicine. DNA was extracted
      and regions of the 16S-23S rRNA intergenic transcribed spacer (ITS) region and
      the pap31 and gltA genes were amplified by polymerase chain reaction (PCR) using
      Bartonella-specific primers. IIF was performed using a primary Bartonella
      henselae monoclonal antibody to localize B. henselae in tissues of PCR-positive
      dogs. Bartonella vinsonii subsp. berkhoffii was amplified from 1/17 (5.8%)
      control tissues and B. henselae was amplified from 4/29 (13.8%) CCH tissues. The
      prevalence of B. vinsonii subsp. berkhoffii (P = 0.37) or B. henselae (P = 0.28)
      did not vary statistically between study groups. B. henselae could be visualized
      in 2/4 (50.0%) CCH tissues using IIF. Based on this study, Bartonella spp. are
      unlikely to cause CCH. 

PMID- 25980842
TI  - Systematic review of decreased intracranial pressure with optimal head elevation
      in postcraniotomy patients: a meta-analysis.
AB  - AIM: To determine an optimal head elevation degree to decrease intracranial
      pressure in postcraniotomy patients by meta-analysis. BACKGROUND: A change in
      head position can lead to a change in intracranial pressure; however, there are
      conflicting data regarding the optimal degree of elevation that decreases
      intracranial pressure in postcraniotomy patients. DESIGN: Quantitative systematic
      review with meta-analysis following Cochrane methods. DATA SOURCES: The data were
      collected during 2014; three databases (PubMed, Embase and China National
      Knowledge Internet) were searched for published and unpublished studies in
      English. The bibliographies of the articles were also reviewed. The inclusion
      criteria referred to different elevation degrees and effects on intracranial
      pressure in postcraniotomy patients. REVIEW METHODS: According to pre-determined
      inclusion criteria and exclusion criteria, two reviewers extracted the eligible
      studies using a standard data form. RESULTS: These included a total of 237
      participants who were included in the meta-analysis. (1) Compared with 0 degree:
      10, 15, 30 and 45 degrees of head elevation resulted in lower intracranial
      pressure. (2) Intracranial pressure at 30 degrees was not significantly different
      in comparison to 45 degrees and was lower than that at 10 and 15 degrees.
      CONCLUSION: Patients with increased intracranial pressure significantly
      benefitted from a head elevation of 10, 15, 30 and 45 degrees compared with 0
      degrees. A head elevation of 30 or 45 degrees is optimal for decreasing
      intracranial pressure. Research about the relationship of position changes and
      the outcomes of patient primary diseases is absent.

PMID- 25980843
TI  - Implications of palonosetron in elderly patients undergoing laparoscopic
      cholecystectomy with respect to its anti-shivering effect.
AB  - BACKGROUND: The elderly are vulnerable to hypothermia and have a higher risk of
      cardiovascular events induced by marked increases in oxygen consumption due to
      shivering. Five-hydroxytryptamine-3 (5-HT3) receptor antagonists have been
      previously reported to reduce post-anesthesia shivering. AIM: In the present
      study, the authors investigated the effects of palonosetron, a new-generation 5
      HT3 antagonist, on core hypothermia and the incidence of shivering after
      laparoscopic cholecystectomy in elderly patients. METHODS: Forty-eight patients
      (65-80 years) were randomly assigned to one of two groups and administered
      palonosetron 0.075 mg (palonosetron group, n = 24) or the same volume of normal
      saline (control group, n = 24) before anesthesia induction. Core body
      temperatures and hemodynamic variables were monitored during and after operation.
      Post-anesthetic shivering (PAS) and pain scores were obtained in a post
      anesthetic care unit. RESULTS: Intraoperative esophageal temperature changed
      significantly over time (P = 0.010), but significant intergroup difference in
      change was not observed (P = 0.706). Furthermore, shivering frequencies were
      similar in the two groups (P = 0.610). However, postoperative pain scores at 30
      min after entering the post-anesthesia care unit were significantly lower in the
      palonosetron group (P = 0.002). DISCUSSION: Regardless of the previously reported
      anti-shivering effect of 5-HT3 receptor antagonists, pre-operative palonosetron
      0.075 mg did not influence perioperative hypothermia or PAS in this study. This
      discrepancy might be due to the dose responsiveness of palonosetron to PAS and
      relatively low incidence of PAS in the elderly. CONCLUSIONS: Pre-operative
      administration of palonosetron 0.075 mg did not influence perioperative
      hypothermia or post-anesthesia shivering in elderly patients undergoing
      laparoscopic cholecystectomy. However, palonosetron might be beneficial for
      reducing early postoperative pain in elderly patients with opioid-based patient
      controlled analgesia.

PMID- 25980844
TI  - Importance of sex and gender in atherosclerosis and cardiovascular disease.

PMID- 25980845
TI  - Keynotes.

PMID- 25980847
TI  - The importance of architectures for interoperability.
AB  - The paradigm changes health systems are faced with result in highly complex and
      distributed systems requiring flexibility, autonomy, but first of all advanced
      interoperability. In that context, understanding the architecture of the system
      to be supported as well as the process to meet the intended business objectives
      is crucial. Unfortunately, there is a lot of confusion around the term
      architecture, which doesn't facilitate the integration of systems. Using a
      reference architecture model and framework, relevant existing architectural
      approaches are analyzed, compared and critically discussed, but also harmonized
      using a reference architectural model and framework. 

PMID- 25980846
TI  - H2020 EU Research & Innovation Program Boost the Transfer of Technological
      Breakthroughs, Enable New Solutions for Personalised Health and Impact the
      Industry and Healthcare Systems.
AB  - Our Healthcare systems worldwide are facing grand challenges that can be
      addressed by intelligent, miniaturized and interconnected devices. Many of
      today's pharmaceutical drugs create bigger problems than solutions, as drugs help
      only 40% of the patients and kill, in the USA alone, over 100,000 people per
      year. The widespread use of antibiotics has led to new strands of bacteria that
      defy all known antibiotics and kill well over 100,000 people yearly in the world.
      Outbreaks of infections by new viruses and anti-resistant bacteria are expected
      with even more grave consequences. The quality of food around the world is
      steadily deteriorating, as the soils are becoming depleted of essential nutrients
      and contain increasing amounts of pesticides, herbicides and fungicides. Our
      environment is burdened with 2.5 billion tonnes of chemicals per year that
      accumulate in the soil, groundwater, rivers and seas, and eventually end up in
      our food and our drinking water. As a consequence, there is a strong increase in
      the incidence of diseases hardly known fifty years ago. In parallel, an
      increasing number of people are taking the responsibility for their health and
      well-being in their own hands and are looking for mobile and in-obtrusive ways to
      objectively monitor their health status. The development of intelligent,
      miniaturized systems, by the heterogeneous integration of technologies such as
      micro- and nano-electronics, photonics, biotechnology, materials and information
      & communication, addresses these issues and has received intensive public support
      in the EU over the past two decades in the FP6 and FP7 programs. Proven concepts
      and functional prototypes exist with the potential to create new opportunities to
      improve our healthcare systems, in particular personalized or precision medicine.
      These device concepts offer unique abilities to sense, detect, analyze,
      communicate, respond, and monitor phenomena from the macro (e.g. body, tissues)
      to the nano scale (e.g. molecules, genes) on the spot, with short response times.
      For the majority of the projects, the planning for the next phase of prototype
      validation, through product design, supply chain setup, user targeting, clinical
      validation and commercial roll-out is now taking full attention. However,
      significant hurdles exist in the successful translation of the new technology to
      new products. As these technologies are new-to-the-world the resulting products
      carry a high risk, often necessitating the creation of new companies. Therefore
      the EU has developed the Horizon 2020 program as a framework for technology
      development and new business creation. Horizon 2020 is focusing on support for
      technology transfer, and on building ecosystems and value chains to ensure
      shorter times-to-market, thus enabling a higher impact of knowledge-based
      technologies. This paper will argue the necessity of developing these new class
      of devices, discuss its state-of-the-art, and the challenges for the
      implementation of Horizon 2020 and the new opportunities in intelligent
      miniaturized systems for pHealth. 

PMID- 25980849
TI  - Invited papers.

PMID- 25980848
TI  - Technology Ready to be Launched, but is there a Payer? Challenges for
      Implementing eHealth in Sweden.
AB  - The development of a sustainable, high-quality, affordable health care is today a
      high priority for many actors in the society. This is to ensure that we will
      continue to afford to care for the growing portion of elderly in our population.
      One solution is to enable the individual's power over her own health or illness,
      and participation in her own care. There are evidently opportunities with the
      rapid development of eHealth and wearable sensors. Tracking and measuring vital
      data can help to keep people out of the hospital. Loads of data is generated to
      help us understand disease, to provide us with early diagnostics and warnings. It
      is providing us with possibilities to collect and capture the true health status
      of individuals. Successful technologies demonstrate savings, acceptance among
      users and improved access to healthcare. But there are also challenges.
      Implementing new technologies in health care is difficult. Researchers from
      around the world are reporting on similar problems, such as reimbursement,
      interoperability, usability and regulatory issues. This paper will discuss a few
      of these implementation challenges as well as a few of the efforts in meeting
      them. To conclude, eHealth solutions can contribute to patient empowerment and a
      sustainable health care. Our assumption is however, that as long as we do not
      face the implementation challenges and invest in overcoming the pressing
      obstacles, society will not be able, or willing, to pay for the solutions. 

PMID- 25980850
TI  - The new role of patients in future health settings.
AB  - Health is wide concept covering a person's physical, mental and social well
      being. Traditionally, regulated healthcare has been the main source for curative
      and preventive service offered to patients. Healthcare is in transition, however.
      Paradigms such as patient empowerment and patient in the centre as well as in
      home care service are changing processes and locations healthcare services are
      offered. Parallel to healthcare, new service models such as pHealth, ubiquitous
      healthcare, and digital medicine are developing. In the near future, technology
      enables the creation of a personal digital health dossier (e.g. digital patient
      and virtual patient model) for any individual. This dossier is stored and used in
      the unsecure information space. This all means that the traditional paternalistic
      patient model where patient is a passive object for regulated healthcare services
      will not work in future pHealth and digital health anymore. Instead, the new
      patient role (e.g. pHealth user or health consumer role) is dynamic, context
      aware and participatory. The pHealth user can also have many roles at the same
      time, such as the role of informed chooser, decision maker, and personal health
      coordinator. This requires that the pHealth user can make information-based
      meaningful decisions before starting to use health services, and that he or she
      can trust on service providers by having evidence-based and reliable information
      about the quality and health impact of the services offered. A big challenge is
      that pHealth and digital health take place in unsecure information space where
      current healthcare specific laws, regulations, and medical ethics are
      insufficient to guarantee users' autonomy and privacy as well as the application
      of fair information and ethical principles when processing personal health
      information. A new ethical, legal and technical framework is needed. One of the
      prerequisites successful pHealth and digital health has to meet is the
      possibility to create information based on trustworthy relationship between
      service user and service providers. Furthermore, a trusted information platform
      is inevitable. 

PMID- 25980851
TI  - mHealth in Low- and Middle-Income Countries: Status, Requirements and Strategies.
AB  - Recent studies demonstrate the potential of Mobile Health (mHealth) to improve
      quality of care and efficiency in low- and middle- income countries (LMIC).
      However, strong evidence of their impact, especially in large scale projects is
      still missing. The objective of this paper is to provide an overview about the
      current status of mHealth in LMIC, and to identify Requirements and possible
      Strategies to strength their health systems. A search in Pubmed was performed,
      which resulted in 427 articles. Restricting the search to review papers published
      during the last 5 years, 72 publications were identified and characterized, and
      the more relevant articles analyzing mHealth use, impact and/or adoption in LMIC
      from a more generic perspective were analyzed in detail. Finally, based on the
      literature, and complemented with the authors own reflections and experience,
      mHealth challenges and strategies were identified and presented according to the
      WHO Health Systems Framework which identifies six main lines of action to improve
      the performance of health systems: service delivery, health workforce, health
      information systems, essential medical products and technologies, health
      financing and governance. 

PMID- 25980852
TI  - Signal processing.

PMID- 25980853
TI  - ECG Artifact Removal from Surface EMG Signal Using an Automated Method Based on
      Wavelet-ICA.
AB  - This study aims at proposing an efficient method for automated
      electrocardiography (ECG) artifact removal from surface electromyography (EMG)
      signals recorded from upper trunk muscles. Wavelet transform is applied to the
      simulated data set of corrupted surface EMG signals to create multidimensional
      signal. Afterward, independent component analysis (ICA) is used to separate ECG
      artifact components from the original EMG signal. Components that correspond to
      the ECG artifact are then identified by an automated detection algorithm and are
      subsequently removed using a conventional high pass filter. Finally, the results
      of the proposed method are compared with wavelet transform, ICA, adaptive filter
      and empirical mode decomposition-ICA methods. The automated artifact removal
      method proposed in this study successfully removes the ECG artifacts from EMG
      signals with a signal to noise ratio value of 9.38 while keeping the distortion
      of original EMG to a minimum. 

PMID- 25980854
TI  - Noise Reduction for a MEMS-Gyroscope-Based Head Mouse.
AB  - In this paper, four different signal processing algorithms which can be applied
      to reduce the noise from a MEMS-gyroscope-based computer head mouse are
      presented. MEMS-gyroscopes are small, light, cheap and widely used in many
      electrical products. MultiPos, a MEMS-gyroscope-based computer head mouse system
      was designed for persons with movement disorders. Noise such as physiological
      tremor and electrical noise is a common problem for the MultiPos system. In this
      study four different signal processing algorithms were applied and evaluated by
      simulation in MATLAB and implementation in a dsPIC, with aim to minimize the
      noise in MultiPos. The algorithms were low-pass filter, Least Mean Square (LMS)
      algorithm, Kalman filter and Weighted Fourier Linear Combiner (WFLC) algorithm.
      Comparisons and system tests show that these signal processing algorithms can be
      used to improve the MultiPos system. The WFLC algorithm was found the best method
      for noise reduction in the application of a MEMS-gyroscope-based head mouse. 

PMID- 25980855
TI  - Heart rate measurement as a tool to quantify sedentary behavior.
AB  - Sedentary work is very common today. The aim of this pilot study was to attempt
      to differentiate between typical work situations and to investigate the
      possibility to break sedentary behavior, based on physiological measurement among
      office workers. Ten test persons used one heart rate based activity monitor
      (Linkura), one pulse oximeter device (Wrist) and one movement based activity
      wristband (Fitbit Flex), in different working situations. The results showed that
      both heart rate devices, Linkura and Wrist, were able to detect differences in
      heart rate between the different working situations (resting, sitting, standing,
      slow walk and medium fast walk). The movement based device, Fitbit Flex, was only
      able to separate differences in steps between slow walk and medium fast walk. It
      can be concluded that heart rate measurement is a promising tool for quantifying
      and separating different working situations, such as sitting, standing and
      walking. 

PMID- 25980856
TI  - EmoBurnout: An Approach for Supporting Burnout Syndrome Diagnosis.
AB  - Burnout is scientifically a work related syndrome which consists of three
      dimensions: emotional exhaustion, depersonalization and reduced professional
      efficacy. Different instruments for the diagnosis of burnout exist, accompanied
      by many associated problems, however. This paper describes a proposal aiming at
      supporting the diagnosis of burnout using measures complementary to the Maslach
      Burnout Inventory (MBI). It specifically focuses on emotions detection to provide
      useful information that contributes to the decision making process about the
      syndrome. 

PMID- 25980857
TI  - Interoperable ICT and Telemedicine.

PMID- 25980858
TI  - A generic architecture for an adaptive, interoperable and intelligent type 2
      diabetes mellitus care system.
AB  - Chronic diseases such as Type 2 Diabetes Mellitus (T2DM) constitute a big burden
      to the global health economy. T2DM Care Management requires a multi-disciplinary
      and multi-organizational approach. Because of different languages and
      terminologies, education, experiences, skills, etc., such an approach establishes
      a special interoperability challenge. The solution is a flexible, scalable,
      business-controlled, adaptive, knowledge-based, intelligent system following a
      systems-oriented, architecture-centric, ontology-based and policy-driven
      approach. The architecture of real systems is described, using the basics and
      principles of the Generic Component Model (GCM). For representing the functional
      aspects of a system the Business Process Modeling Notation (BPMN) is used. The
      system architecture obtained is presented using a GCM graphical notation, class
      diagrams and BPMN diagrams. The architecture-centric approach considers the
      compositional nature of the real world system and its functionalities, guarantees
      coherence, and provides right inferences. The level of generality provided in
      this paper facilitates use case specific adaptations of the system. By that way,
      intelligent, adaptive and interoperable T2DM care systems can be derived from the
      presented model as presented in another publication. 

PMID- 25980860
TI  - Innovative materials and methodologies.

PMID- 25980859
TI  - Specializing architectures for the type 2 diabetes mellitus care use cases with a
      focus on process management.
AB  - The development of software supporting inter-disciplinary systems like the type 2
      diabetes mellitus care requires the deployment of methodologies designed for this
      type of interoperability. The GCM framework allows the architectural description
      of such systems and the development of software solutions based on it. A first
      step of the GCM methodology is the definition of a generic architecture, followed
      by its specialization for specific use cases. This paper describes the
      specialization of the generic architecture of a system, supporting Type 2
      diabetes mellitus glycemic control, for a pharmacotherapy use case. It focuses on
      the behavioral aspect of the system, i.e. the policy domain and the definition of
      the rules governing the system. The design of this architecture reflects the
      inter-disciplinary feature of the methodology. Finally, the resulting
      architecture allows building adaptive, intelligent and complete systems. 

PMID- 25980861
TI  - Users perspectives on interactive distance technology enabling home-based motor
      training for stroke patients.
AB  - The aim of this work has been to develop a technical support enabling home-based
      motor training after stroke. The basis for the work plan has been to develop an
      interactive technical solution supporting three different groups of stroke
      patients: (1) patients with stroke discharged from hospital with support from
      neuro team; (2) patients with stroke whose support from neuro team will be phased
      out and (3) patients living with impaired motor functions long-term. The
      technology has been developed in close collaboration with end-users using a
      method earlier evaluated and described [12]. This paper describes the main
      functions of the developed technology. Further, results from early user-tests
      with end-users, performed to identify needs for improvements to be carried out
      during further technical development. The developed technology will be tested
      further in a pilot study of the safety and, usefulness of the technology when
      applied as a support for motor training in three different phases of the post
      stroke rehabilitation process. 

PMID- 25980862
TI  - Psychologist in a pocket: towards depression screening on mobile phones.
AB  - Depression is the most prevalent clinical disorder and one of the main causes of
      disability. This makes early detection of depressive symptoms critical in its
      prevention and management. This paper presents and discusses the development of
      Psychologist in a Pocket (PiaP), a mental mHealth application for Android which
      screens and monitors for these symptoms, and-given the explicit permission of the
      user-alerts a trusted contact such as the mental health professional or a close
      friend, if it detects symptoms. All text inputted electronically-such as short
      message services, emails, social network posts-is analyzed based on keywords
      related to depression based on DSM-5 and ICD criteria as well as Beck's Cognitive
      Theory of Depression and the Self-Focus Model. Data evaluation and collection
      happen in the background, on-device, without requiring any user involvement.
      Currently, the application is in an early prototype phase entering initial
      clinical validation. 

PMID- 25980863
TI  - Smartphone serious games for vision and hearing assessment.
AB  - Falls are the second leading cause of accidental injury deaths worldwide. In this
      paper, it is intended to define methodologies that permit the evaluation of two
      potential factors which might have an impact on fall risk, these are: visual and
      hearing loss. The aim of the work developed is not to replace clinic visits, but
      to offer the user the means to continue the tracking of his vision and hearing at
      home, during the long time intervals between clinical tests. Tests conducted in a
      sample of our target users indicate a good ability to measure vision and hearing
      using an android smartphone and the proposed methodologies. While some tests
      require further validation, promising results were achieved in the most common
      tests for vision and hearing, presenting a good correlation between the system's
      results when compared to the traditional tests (for distance visual acuity) and
      the data gathered from the users (for hearing tests). 

PMID- 25980865
TI  - Solutions for Personalized Care and mHealth Applications.

PMID- 25980864
TI  - An in vitro Study of Protein Adsorption to Biocompatible Coatings.
AB  - The motivation for these experiments was to investigate the amount and type of
      protein adsorption on surfaces that can be used as protective coatings on
      membrane based in vivo devices. Adsorption of proteins to a selection of
      biocompatible coatings (titanium oxide, diamond-like carbon, parylene C) and
      typical construction materials for Micro Electro Mechanical Systems (silicon,
      silicon nitride), were investigated during in vitro tests. The samples were
      incubated in human liver extract and bovine serum albumin (BSA) for up to 12
      hours. The amount of protein adsorption was found to be low for all surfaces.
      Measurements of bound Iodine-125 labeled BSA, showed a protein adsorption of up
      to 0.2 MUg BSA/cm<sup>2</sup>. The specific proteins adsorbed to the surfaces
      after incubation in human liver extract were identified using mass spectrometry.
      Most of the identified adsorbed proteins were intracellular, but plasma proteins
      like Immunoglobulin (Ig) and serum albumin as well as hemoglobin were also
      identified. 

PMID- 25980866
TI  - Mobile ECG Systems and Cardiovascular Risk: A Systematic Review.
AB  - PROBLEM: Cardiovascular diseases (CVD) are the number one cause of death
      globally. According to WHO (World Health Organization), 80% of these deaths occur
      in low- and middle-income countries. CVDs are associated to risk factors such as
      obesity, smoking, sedentary lifestyle, and others. The scientific community keeps
      searching for new parameters, like ECG signal analysis, to improve cardiovascular
      risk evaluation. OBJECTIVE: This article aims at providing a systematic review of
      developed mobile Electrocardiogram (ECG) systems and the relevance of ECG for the
      assessment of cardiovascular risk. METHODS: A systematic review of two databases
      (PubMed and IEEEXplore) was carried out. RESULTS: This article provides an
      analysis of 10 studies describing mobile ECG systems developed in the last 10
      years, and 6 studies analyzing the effectiveness of ECG as a parameter to assess
      cardiovascular risk. CONCLUSIONS: The systematic review demonstrated that there
      are no mobile ECG systems used for cardiovascular risk assessment. Furthermore,
      the review indicates that there is scientific evidence about the effectiveness of
      ECG as a parameter for cardiovascular risk evaluation, but only in some specific
      cases.

PMID- 25980867
TI  - Towards Bringing EEG Research and Diagnostics out of the Lab.
AB  - Bringing brain research tools like EEG devices out of the lab into the pockets of
      practitioners and researchers may fundamentally change the way we perform
      diagnostics and research. While most of the current techniques are limited to
      research clinics and require excessive set-up, new consumer EEG devices connected
      to standard, off-the-shelf mobile devices allow us to lift these limitations.
      This allows neuropsychological assessment and research in mobile settings,
      possibly even in remote areas with limited accessibility and infrastructure, thus
      bringing the equipment to the patient, instead of bringing the patient to the
      equipment. We are developing an Android based mobile framework to perform EEG
      studies. By connecting a mobile consumer EEG headset directly to an unmodified
      mobile device, presenting auditory and visual stimuli, as well as user
      interaction, we create a self-contained experimental platform. We complement this
      platform by a toolkit for immediate evaluation of the recorded data directly on
      the device, even without Internet connectivity. Initial results from the
      replication of two Event Related Potentials studies indicate the feasibility of
      the approach. 

PMID- 25980868
TI  - Development of an eating aid - from the user needs to a product.
AB  - In this paper, the development process of an eating aid is described. The
      assistive devices must be worth using. To achieve this, the starting point has
      been the users need. The development started from the needs of an individual
      person, the inventor of the aid. The development has been about increasing the
      positive experience of the aid and decrease negative experience through an
      iterative development process. The development includes several evaluations,
      described in the paper, and as a conclusion, it is important to include the users
      throughout the development process. 

PMID- 25980869
TI  - Wearable and implantable devices and systems.

PMID- 25980870
TI  - A study of different fabrics to increase radar cross section of humans.
AB  - This purpose of the study was to increase the visibility on radar for unprotected
      pedestrians with the aid of conducting fabric. The experiment comprised
      measurements of four types of fabric to determine the radio frequency properties,
      such as radar cross section (RCS) for the vehicle radar frequency 77 GHz and
      transmission (shielding) in the frequency range 3-18 GHz. Two different
      thicknesses of polypyrrole (PPy) nonvowen fabric were tested and one thickness
      for 30 % and 40 % stainless steel fabrics respectively. A jacket with the thinner
      nonvowen material and one with 40 % steel were tested and compared to an
      unmodified jacket in the RCS measurement. The measurement showed an increase in
      RCS of 4 dB for the jacket with the 40 % steel lining compared to the unmodified
      jacket. The transmission measurement was aimed at determining the fabric with the
      highest transmission of an incoming radio wave. The 30 % steel fabric and the two
      thicknesses of the nonvowen fabrics were tested. One practical application is for
      example the use of radar reflective material in search and rescue (SAR) clothes.
      The study showed that the 30 % steel fabric was the best candidate for further
      RCS measurements. 

PMID- 25980871
TI  - Encapsulation for smart textile electronics - humidity and temperature sensor.
AB  - A combined humidity and temperature sensor was packaged by vacuum casting onto
      three different types of textiles; cotton, nylon and a waterproof fabric. This
      was done in order to integrate the sensor in a jacket in a soft and reliable way
      without changing the sensor performance. A membrane was custom made and
      integrated into the device to protect the sensor from the environment. The
      packaged sensors performance was characterized in a climate chamber were the
      relative humidity and temperature ranged from 25 % to 95 % and -10  degrees C to
      75  degrees C respectively. The packaged sensors showed insignificant to limited
      performance degradation. 

PMID- 25980872
TI  - Business model design for a wearable biofeedback system.
AB  - Wearable sensor technologies used to track daily activities have become
      successful in the consumer market. In order for wearable sensor technology to
      offer added value in the more challenging areas of stress-rehab care and
      occupational health stress-related biofeedback parameters need to be monitored
      and more elaborate business models are needed. To identify probable success
      factors for a wearable biofeedback system (Affective Health) in the two mentioned
      market segments in a Swedish setting, we conducted literature studies and
      interviews with relevant representatives. Data were collected and used first to
      describe the two market segments and then to define likely feasible business
      model designs, according to the Business Model Canvas framework. Needs of
      stakeholders were identified as inputs to business model design. Value
      propositions, a key building block of a business model, were defined for each
      segment. The value proposition for occupational health was defined as "A tool
      that can both identify employees at risk of stress-related disorders and
      reinforce healthy sustainable behavior" and for healthcare as: "Providing
      therapists with objective data about the patient's emotional state and motivating
      patients to better engage in the treatment process". 

PMID- 25980873
TI  - Impedance matching wireless power transmission system for biomedical devices.
AB  - For medical application, the efficiency and transmission distance of the wireless
      power transfer (WPT) are always the main concern. Research has been showing that
      the impedance matching is one of the critical factors for dealing with the
      problem. However, there is not much work performed taking both the source and
      load sides into consideration. Both sides matching is crucial in achieving an
      optimum overall performance, and the present work proposes a circuit model
      analysis for design and implementation. The proposed technique was validated
      against experiment and software simulation. Result was showing an improvement in
      transmission distance up to 6 times, and efficiency at this transmission distance
      had been improved up to 7 times as compared to the impedance mismatch system. The
      system had demonstrated a near-constant transfer efficiency for an operating
      range of 2cm-12cm. 

PMID- 25980874
TI  - Intelligent systems.

PMID- 25980875
TI  - Advanced decision support system for older adults.
AB  - Decision support systems are rapidly becoming part of today's healthcare
      delivery. The paradigm has shifted from traditional and manual recording to
      computer-based electronic records and, further, to handheld devices as versatile
      and innovative healthcare monitoring systems. The current study focuses on
      interpreting multiple physical signs and early warning for hospitalized older
      adults so that severe consequences can be minimized. Data from a total of 30
      patients have been collated in New Zealand Hospitals under local and national
      ethics approvals. The system records blood pressure, heart rate (pulse), oxygen
      saturation (SpO2), ear temperature and blood glucose levels from hospitalized
      patients and transfers this information to a web-based software application for
      remote monitoring and further interpretation. Ultimately, this system is aimed to
      achieve a high level of agreement with clinicians' interpretation when assessing
      specific physical signs such as bradycardia, tachycardia, hypertension,
      hypotension, hypoxemia, fever and hypothermia and to generate early warnings. 

PMID- 25980876
TI  - Supervised machine learning algorithms to diagnose stress for vehicle drivers
      based on physiological sensor signals.
AB  - Machine learning algorithms play an important role in computer science research.
      Recent advancement in sensor data collection in clinical sciences lead to a
      complex, heterogeneous data processing, and analysis for patient diagnosis and
      prognosis. Diagnosis and treatment of patients based on manual analysis of these
      sensor data are difficult and time consuming. Therefore, development of Knowledge
      based systems to support clinicians in decision-making is important. However, it
      is necessary to perform experimental work to compare performances of different
      machine learning methods to help to select appropriate method for a specific
      characteristic of data sets. This paper compares classification performance of
      three popular machine learning methods i.e., case-based reasoning, neutral
      networks and support vector machine to diagnose stress of vehicle drivers using
      finger temperature and heart rate variability. The experimental results show that
      case-based reasoning outperforms other two methods in terms of classification
      accuracy. Case-based reasoning has achieved 80% and 86% accuracy to classify
      stress using finger temperature and heart rate variability. On contrary, both
      neural network and support vector machine have achieved less than 80% accuracy by
      using both physiological signals. 

PMID- 25980877
TI  - A personalized health-monitoring system for elderly by combining rules and case
      based reasoning.
AB  - Health-monitoring system for elderly in home environment is a promising solution
      to provide efficient medical services that increasingly interest by the
      researchers within this area. It is often more challenging when the system is
      self-served and functioning as personalized provision. This paper proposed a
      personalized self-served health-monitoring system for elderly in home environment
      by combining general rules with a case-based reasoning approach. Here, the system
      generates feedback, recommendation and alarm in a personalized manner based on
      elderly's medical information and health parameters such as blood pressure, blood
      glucose, weight, activity, pulse, etc. A set of general rules has used to
      classify individual health parameters. The case-based reasoning approach is used
      to combine all different health parameters, which generates an overall
      classification of health condition. According to the evaluation result
      considering 323 cases and k=2 i.e., top 2 most similar retrieved cases, the
      sensitivity, specificity and overall accuracy are achieved as 90%, 97% and 96%
      respectively. The preliminary result of the system is acceptable since the
      feedback; recommendation and alarm messages are personalized and differ from the
      general messages. Thus, this approach could be possibly adapted for other
      situations in personalized elderly monitoring. 

PMID- 25980879
TI  - Security, privacy, safety, trust and ethics.

PMID- 25980878
TI  - A public health decision support system model using reasoning methods.
AB  - PROBLEM: Public health programs must be based on the real health needs of the
      population. However, the design of efficient and effective public health programs
      is subject to availability of information that can allow users to identify, at
      the right time, the health issues that require special attention. OBJECTIVE: The
      objective of this paper is to propose a case-based reasoning model for the
      support of decision-making in public health. RESULTS: The model integrates a
      decision-making process and case-based reasoning, reusing past experiences for
      promptly identifying new population health priorities. A prototype implementation
      of the model was performed, deploying the case-based reasoning framework
      jColibri. CONCLUSIONS: The proposed model contributes to solve problems found
      today when designing public health programs in Colombia. Current programs are
      developed under uncertain environments, as the underlying analyses are carried
      out on the basis of outdated and unreliable data.

PMID- 25980880
TI  - Personalized Message Routing Policy in Pervasive eHealth Applications Based on
      HL7 RIM.
AB  - The design of relevant message routing strategies that provide reliable
      communications between different healthcare actors is deemed among one of the
      most challenging requirements to enhance QoS in eHealth applications. In this
      paper, we propose a data and context-driven model that aims to support the design
      of personalized, intelligent and adaptive eHealth message routing policies. Our
      model is suitably complying with HL7 v3, an international standard for healthcare
      information exchange. In the proposed model, we highlight the sensitivity of
      routing services applications to message, source and target ecosystems contextual
      information. We point out the relevant HL7 Reference Information Model (RIM)
      elements that are related to our research objective which is to deliver the
      message to the right healthcare provider with respect to the required delays for
      message reception, reading and reply, according to the content of the message and
      to the clinical and social situation of the patient. Moreover, we include AmI to
      make the routing policy intelligently adaptive to context changes at run-time. 

PMID- 25980881
TI  - Privacy Management and Networked PPD Systems - Challenges Solutions.
AB  - Modern personal portable health devices (PPDs) become increasingly part of a
      larger, inhomogeneous information system. Information collected by sensors are
      stored and processed in global clouds. Services are often free of charge, but at
      the same time service providers' business model is based on the disclosure of
      users' intimate health information. Health data processed in PPD networks is not
      regulated by health care specific legislation. In PPD networks, there is no
      guarantee that stakeholders share same ethical principles with the user. Often
      service providers have own security and privacy policies and they rarely offer to
      the user possibilities to define own, or adapt existing privacy policies. This
      all raises huge ethical and privacy concerns. In this paper, the authors have
      analyzed privacy challenges in PPD networks from users' viewpoint using system
      modeling method and propose the principle "Personal Health Data under Personal
      Control" must generally be accepted at global level. Among possible
      implementation of this principle, the authors propose encryption, computer
      understandable privacy policies, and privacy labels or trust based privacy
      management methods. The latter can be realized using infrastructural trust
      calculation and monitoring service. A first step is to require the protection of
      personal health information and the principle proposed being internationally
      mandatory. This requires both regulatory and standardization activities, and the
      availability of open and certified software application which all service
      providers can implement. One of those applications should be the independent
      Trust verifier. 

PMID- 25980883
TI  - Opportunities and limitations in using google glass to assist drug dispensing.
AB  - The administration of intravenous drugs is a significant source of medical
      errors. Protocol based care are have been demonstrated to be an efficient way to
      favor best practices and to avoid simple errors such as those related to
      expiration date, hygiene regulation among other. The recent availability of the
      Google Glass, a hands free wearable device offers new opportunities to access
      care protocols at patients' bedside. In this article, we present a prototype
      application for displaying care protocols developed through a user centered
      design. The software enables the navigation through the different steps of care
      protocols and their validation using barcodes. Three interactions paradigms,
      tactile, vocal and by eye blink are proposed in order to provide hands free
      manipulation when necessary. The realization of a concrete project revealed some
      limitations that should be taken in account in order to ensure the proper
      behavior of the tool. If no formal evaluation has been performed, the first
      feedbacks are very positive and encourage us to go forward and test the tool in
      real care situations. 

PMID- 25980884
TI  - Wearable Sensors in Medical Education: Supporting Hand Hygiene Training with a
      Forearm EMG.
AB  - Lack of proper hand hygiene is a common source of hospital acquired infections.
      Training and evaluating efficiency in hand washing is therefore an important part
      of medical education. Here, we propose to use the Myo wearable armband to measure
      correctness of hand washing for mobile learning. Myo's sensors are designed in
      order to recognize the activity of the forearm, palm and fingers. Using signal
      processing and machine learning, the quality of the hand washing process can be
      estimated and used as evaluation in medical teaching. The project is in its
      initial phase, thus we present preliminary results and a vision of future
      development. 

PMID- 25980885
TI  - Prediction of Heart Attack Risk Using GA-ANFIS Expert System Prototype.
AB  - The aim of this research is to develop a novel GA-ANFIS expert system prototype
      for classifying heart disease degree of a patient by using heart diseases
      attributes (features) and diagnoses taken in the real conditions. Thirteen
      attributes have been used as inputs to classifiers being based on Adaptive Neuro
      Fuzzy Inference Systems (ANFIS) for the first level of fuzzy model optimization.
      They are used as inputs in Genetic Algorithm (GA) for the second level of fuzzy
      model optimization within GA-ANFIS system. GA-ANFIS system performs optimization
      in two steps. Modelling and validating of the novel GA-ANFIS system approach is
      performed in MATLAB environment. We compared GA-ANFIS and ANFIS results. The
      proposed GA-ANFIS model with the predicted value technique is more efficient when
      diagnosis of heart disease is concerned, as well the earlier method we got by
      ANFIS model. 

PMID- 25980886
TI  - Smart wireless sensor for physiological monitoring.
AB  - Presented is a wireless body sensor capable of measuring local potential
      differences on a body surface. By using on-sensor signal processing capabilities,
      and developed algorithms for off-line signal processing on a personal computing
      device, it is possible to record single channel ECG, heart rate, breathing rate,
      EMG, and when three sensors are applied, even the 12-lead ECG. The sensor is
      portable, unobtrusive, and suitable for both inpatient and outpatient monitoring.
      The paper presents the sensor's hardware and results of power consumption
      analysis. The sensor's capabilities of recording various physiological parameters
      are also presented and illustrated. The paper concludes with envisioned sensor's
      future developments and prospects. 

PMID- 25980887
TI  - Development of a metabolic syndrome personal health record system.
AB  - According to the International Diabetes Federation (IDF), a quarter of the world
      population is affected with metabolic syndrome (MS). The paper describes the
      development process of a Personal Health Record System (PHR) for the management
      of MS. Following the recommendations of ISO 9241-210:2010, a PHR for the
      promotion of physical activity and healthy nutrition was implemented. 

PMID- 25980888
TI  - A Generic System-Level Framework for Self-Serve Health Monitoring System through
      Internet of Things (IoT).
AB  - Sensor data are traveling from sensors to a remote server, data is analyzed
      remotely in a distributed manner, and health status of a user is presented in
      real-time. This paper presents a generic system-level framework for a self-served
      health monitoring system through the Internet of Things (IoT) to facilities an
      efficient sensor data management. 

PMID- 25980889
TI  - Personalized decision support system based on clinical practice guidelines.
AB  - Personalized medicine is a broad and rapidly advancing field of health care that
      is informed by each person's unique clinical, genetic, genomic, and environmental
      information. Health care that embraces personalized medicine is an integrated,
      coordinated, evidence based approach to individualizing patient care across the
      continuum. It is very important to make the right treatment decision but before
      that to obtain a good diagnosis. There are several clinical forms of disease
      whose symptoms vary depending on the age and etiology. In this study, we
      investigated and evaluated a model framework, for personalized diagnostic
      decisions, based on Case Based Fuzzy Cognitive Map (CBFCM, a cognitive process
      applying the main features of fuzzy logic and neural processors to situations
      involving imprecision and uncertain descriptions, in a similar way to intuitive
      human reasoning. We explored the use of this method for modelling clinical
      practice guidelines. 

PMID- 25980890
TI  - Tele-monitoring of the rehabilitation progress in stroke patients.
AB  - Preservation of mobility in conjunction with an independent life style is one of
      the major goals of rehabilitation after stroke. The Rehab@Home framework shall
      support the continuation of rehabilitation in the domestic area. The framework
      consists of instrumented insoles, wireless linked to a tablet PC, a server and a
      web-interface for medical experts. The rehabilitation progress is estimated via
      automated analysis of movement data from standardized assessment tests which are
      executed via the tablet PC application designed according to the needs of stroke
      patients. Initial evaluation of the analysis algorithms shows reproducible
      results for the overall time of the Timed Up & Go Test. Therefore it is assumed
      that the Rehab@Home framework is applicable as monitoring tool for the gait
      rehabilitation progress in stroke patients. 

PMID- 25980894
TI  - New approaches to nanoparticle sample fabrication for atom probe tomography.
AB  - Due to their unique properties, nano-sized materials such as nanoparticles and
      nanowires are receiving considerable attention. However, little data is available
      about their chemical makeup at the atomic scale, especially in three dimensions
      (3D). Atom probe tomography is able to answer many important questions about
      these materials if the challenge of producing a suitable sample can be overcome.
      In order to achieve this, the nanomaterial needs to be positioned within the end
      of a tip and fixed there so the sample possesses sufficient structural integrity
      for analysis. Here we provide a detailed description of various techniques that
      have been used to position nanoparticles on substrates for atom probe analysis.
      In some of the approaches, this is combined with deposition techniques to
      incorporate the particles into a solid matrix, and focused ion beam processing is
      then used to fabricate atom probe samples from this composite. Using these
      approaches, data has been achieved from 10-20 nm core-shell nanoparticles that
      were extracted directly from suspension (i.e. with no chemical modification) with
      a resolution of better than +/- 1 nm.

PMID- 25980895
TI  - Characterization of ion-irradiation-induced nanodot structures on InP surfaces by
      atom probe tomography.
AB  - Surfaces of InP were bombarded by 1.9 keV Ar(+) ions under normal incidence. The
      total accumulated ion fluence the samples were exposed to was varied from 1 *
      10(17) cm(-2) to 3 * 10(18)cm(-2) and ion flux densities f of (0.4-2) * 10(14)
      cm(-2) s(-1) were used. Nanodot structures were found to evolve on the surface
      from these ion irradiations, their dimensions however, depend on the specific
      bombardment conditions. The resulting surface morphology was examined by atomic
      force microscopy (AFM). As a function of ion fluence, the mean radius, height,
      and spacing of the dots can be fitted by power-law dependences. In order to
      determine possible local compositional changes in these nanostructures induced by
      ion impact, selected samples were prepared for atom probe tomography (APT). The
      results indicate that by APT the composition of individual InP nanodots evolving
      under ion bombardment could be examined with atomic spatial resolution. At the
      InP surface, the values of the In/P concentration ratio are distinctly higher
      over a distance of ~1 nm and amount to 1.3-1.8. However, several aspects critical
      for the analyses were identified: (i) because of the small dimensions of these
      nanostructures a successful tip preparation proved very challenging. (ii) The
      elemental compositions obtained from APT were found to be influenced pronouncedly
      by the laser pulse energy; typically, low energies result in the correct
      stoichiometry whereas high ones lead to an inhomogeneous evaporation from the
      tips and deviations from the nominal composition. (iii) Depending again on the
      laser energy, a prolific emission of Pn cluster ions was observed, with n <= 11.

PMID- 25980896
TI  - Psychological distress related to BRCA testing in ovarian cancer patients.
AB  - An increasing demand for genetic testing has moved the procedure from highly
      selected at-risk individuals, now also including cancer patients for treatment
      associated testing. The heritable fraction of ovarian cancer is more than 10%,
      and our department has offered BRCA testing to such patients irrespective of
      family history since 2002. This study examined potential psychosocial distress
      associated with this procedure using The Multidimensional Impact of Cancer Risk
      Assessment (MICRA) questionnaire and other patient-rated generic distress
      instruments. Patients were divided into four groups according to cancer risk:
      mutation carriers, own history of breast cancer and ovarian cancer, family
      history of breast cancer and/or ovarian cancer, and patients without family
      history. In a postal survey, 354 patients responded. Good acceptance of the MICRA
      was observed, and previously described good psychometric properties were
      confirmed. A significant association between MICRA total score and receiving a
      positive BRCA test result was found. No significant between-group differences
      were observed with generic distress instruments. Time since cancer diagnosis,
      test result, and survey showed no significant associations with MICRA scores.
      Internal consistencies of instruments were adequate. Exploratory and confirmatory
      factor analyses showed adequate fit indices for a three factor solution of the
      MICRA, but further refinement of the items should be considered. In conclusion,
      the specific types of worry and distress most relevant to receiving genetic
      testing irrespective of family history were not captured by the generic distress
      instruments. The MICRA was supported as a useful tool for detection of mental
      distress related to genetic testing and risk evaluation.

PMID- 25980898
TI  - Trimetallic PtCuCo hollow nanospheres with a dendritic shell for enhanced
      electrocatalytic activity toward ethylene glycol electrooxidation.
AB  - In this work, by utilizing galvanic replacement reaction, a simple method for the
      synthesis of trimetallic PtCuCo hollow nanospheres with a dendritic shell is
      demonstrated. The compositions of the nanospheres can be well controlled, and the
      electrocatalytic activity can also be modulated by adjusting their compositions.
      Electrocatalytic results show that all of the as-prepared trimetallic PtCuCo
      nanomaterials show better catalytic performance toward ethylene glycol
      electrooxidation than the commercial catalyst. 

PMID- 25980897
TI  - A functional HOTAIR rs920778 polymorphism does not contributes to gastric cancer
      in a Turkish population: a case-control study.
AB  - An aberrant up-regulation of HOX transcript antisense intergenic RNA (HOTAIR), a
      long non-coding RNA (lncRNA), is associated with human cancers including gastric
      cancer (GC) and worse clinicopathological features. A naturally occurring
      functional single nucleotide polymorphism (SNP) rs920,778 (C->T) in the intronic
      enhancer of HOTAIR gene has been demonstrated to affect HOTAIR expression and
      cancer susceptibility. To investigate the association of the HOTAIR rs920778
      polymorphism on the risk of GC susceptibility in Turkish population, a hospital
      based case-control study was carried out consisting of 104 GC and 209 healthy
      control subjects matched on age and gender. The genotype frequency of HOTAIR
      rs920778 polymorphism was determined by using TaqMan Real-Time Polymerase Chain
      Reaction. No statistically significant differences were found in the allele or
      genotype distributions of the HOTAIR rs920778 polymorphism among GC and healthy
      control subjects (P > 0.05). Our results demonstrate that the HOTAIR rs920778
      polymorphism has not been in any major role in genetic susceptibility to gastric
      carcinogenesis, at least in the population studied here. Independent studies are
      needed to validate our findings in a larger series, as well as in patients of
      different ethnic origins. 

PMID- 25980899
TI  - Multipotent stromal cells derived from common marmoset Callithrix jacchus within
      alginate 3D environment: Effect of cryopreservation procedures.
AB  - Multipotent stromal cells derived from the common marmoset monkey Callithrix
      jacchus (cjMSCs) possess high phylogenetic similarity to humans, with a great
      potential for preclinical studies in the field of regenerative medicine. Safe and
      effective long-term storage of cells is of great significance to clinical and
      research applications. Encapsulation of such cell types within alginate beads
      that can mimic an extra-cellular matrix and provide a supportive environment for
      cells during cryopreservation, has several advantages over freezing of cells in
      suspension. In this study we have analysed the effect of dimethyl sulfoxide
      (Me2SO, 2.5-10%, v/v) and pre-freeze loading time of alginate encapsulated cjMSCs
      in Me2SO (0-45 min) on the viability and metabolic activity of the cells after
      freezing using a slow cooling rate (-1 degrees C/min). It was found that these
      parameters affect the stability and homogeneity of alginate beads after thawing.
      Moreover, the cjMSCs can be frozen in alginate beads with lower Me2SO
      concentration of 7.5% after 30 min of loading, while retaining high
      cryopreservation outcome. We demonstrated the maximum viability, membrane
      integrity and metabolic activity of the cells under optimized, less cytotoxic
      conditions. The results of this study are another step forward towards the
      application of cryopreservation for the long-term storage and subsequent
      applications of transplants in cell-based therapies.

PMID- 25980900
TI  - One-year efficacy and safety of a fixed combination of insulin degludec and
      liraglutide in patients with type 2 diabetes: results of a 26-week extension to a
      26-week main trial.
AB  - AIMS: To confirm, in a 26-week extension study, the sustained efficacy and safety
      of a fixed combination of insulin degludec and liraglutide (IDegLira) compared
      with either insulin degludec or liraglutide alone, in patients with type 2
      diabetes. METHODS: Insulin-naive adults with type 2 diabetes randomized to once
      daily IDegLira, insulin degludec or liraglutide, in addition to metformin +/-
      pioglitazone, continued their allocated treatment in this preplanned 26-week
      extension of the DUAL I trial. RESULTS: A total of 78.8% of patients (1311/1663)
      continued into the extension phase. The mean glycated haemoglobin (HbA1c)
      concentration at 52 weeks was reduced from baseline by 1.84% (20.2 mmol/mol) for
      the IDegLira group, 1.40% (15.3 mmol/mol) for the insulin degludec group and
      1.21% (13.2 mmol/mol) for the liraglutide group. Of the patients on IDegLira, 78%
      achieved an HbA1c of <7% (53 mmol/mol) versus 63% of the patients on insulin
      degludec and 57% of those on liraglutide. The mean fasting plasma glucose
      concentration at the end of the trial was similar for IDegLira (5.7 mmol/l) and
      insulin degludec (6.0 mmol/l), but higher for liraglutide (7.3 mmol/l). At 52
      weeks, the daily insulin dose was 37% lower with IDegLira (39 units) than with
      insulin degludec (62 units). IDegLira was associated with a significantly greater
      decrease in body weight (estimated treatment difference, -2.80 kg, p < 0.0001)
      and a 37% lower rate of hypoglycaemia compared with insulin degludec. Overall,
      all treatments were well tolerated and no new adverse events or tolerability
      issues were observed for IDegLira. CONCLUSIONS: These 12-month data, derived from
      a 26-week extension of the DUAL I trial, confirm the initial 26-week main phase
      results and the sustainability of the benefits of IDegLira compared with its
      components in glycaemic efficacy, safety and tolerability.

PMID- 25980901
TI  - [Ileocystoplasty, pregnancy and delivery].
AB  - INTRODUCTION: Bladder augmentation is commonly used in neurological and other
      congenital anomalies of the lower urinary tract. In pregnant women, this
      reconstructive surgery may affect pregnancy and delivery. The obstetrical
      consequences of these urological procedures are scarcely reported in literature.
      MATERIAL AND METHOD: Eight pregnancies in 6 pregnant women with ileocystoplasty
      were followed in our institution between 1998 and 2014. RESULTS: Urinary tract
      infections were the most frequent undesirable record event (5 patients, 7
      pregnancies). Obstetrical complications were not more frequent compared to common
      pregnancies. Delivery was programmed at 37WA. Cesarean section was favoured in
      this group although natural delivery is possible. CONCLUSION: Urological
      complications were the major problem in this series. The type of delivery depends
      on the past surgical history and the obstetrical prognosis.

PMID- 25980902
TI  - [Spot urinary protein to creatinine ratio: Which role in preeclampsia
      diagnosis?].
AB  - Preeclampsia remains a serious and feared complication of pregnancy. Its
      diagnosis is confirmed upon detection of hypertension and significant proteinuria
      starting from 20 weeks of gestation. The 24-hour urine collection is considered
      to be the gold standard test for quantitative diagnosis of proteinuria despite
      its downsides. Recent studies have brought into question its accuracy during
      pregnancy as complete samples are hard to get, but above all, as this time
      consuming procedure often delays treatment and may preclude optimal management.
      Several publications looked at the spot urinary protein to creatinine ratio (PCR)
      as a replacement to the 24-hour urine collection. Largely used outside pregnancy,
      this fast and less invasive test seems a compelling alternative. In this paper,
      data from previous meta-analysis and guidelines have been reviewed in an attempt
      to clarify the role of the PCR in clinical practice and elaborate an algorithm in
      case of suspicion of preeclampsia. Thus, this test seems a valid "rule-out test"
      when using the optimal threshold of 30mg/mmol. Higher values require a 24-hour
      urine collection for confirmation. 

PMID- 25980903
TI  - [Contribution of ultrasound signs for the prenatal diagnosis of posterior
      urethral valves: Experience of 3years at the maternity of the Bicetre Hospital].
AB  - OBJECTIVES: Posterior urethral valves (PUV) are the most common cause of renal
      impairment in boys during early childhood. The aim of this study was to evaluate
      the value of ultrasound (US) criteria currently used to diagnose PUV. MATERIALS
      AND METHODS: From 2009 to 2012, 31 patients were referred to the Bicetre Hospital
      after detection of fetal bilateral hydronephrosis in male fetus. The ultrasound
      criteria were bladder dilation, thick-walled bladder, urethral dilation ("keyhole
      sign"), and amniotic fluid volume. Patients were divided in two groups: suspected
      or not to have PUV. RESULTS: US diagnosis of PUV was done in 18 fetuses and
      confirmed in 14 new borns, one of them without prenatal diagnosis. Sensitivity
      and specificity of US scan were 92.8 and 66.7%. The likelihood ratio (LHR) was
      4.8 for a thick-walled bladder, 4.2 for oligohydramnios, 3.6 for the "keyhole
      sign", 2.4 for bladder dilation and 1.6 for ureteral dilation. The first four
      signs were combined in four fetuses, all of them with PUV. CONCLUSION: US scan is
      a very sensitive exam for the diagnosis of PUV but with a low specificity. A
      thick-walled bladder seems to have a better diagnostic performance than the
      "keyhole sign".

PMID- 25980904
TI  - Synergistic defects of UNC13D and AP3B1 leading to adult hemophagocytic
      lymphohistiocytosis.
AB  - A 32-year-old man of non-consanguineous Chinese parentage, with high-grade fever,
      rash, joint pain, nausea, and vomiting, was diagnosed as adult-onset still's
      disease at his initial admission. Although prednisone had been taken, the patient
      presented with recurrent high-grade fever, rash, splenomegaly,
      hypertriglyceridemia, cryptogenic hepatitis, apparently elevated levels of serum
      ferritin(>20,000 MUg/L), which met the proposed HLH diagnostic criteria, 2009.
      Sequence analysis of genomic DNA from the patient's peripheral blood demonstrated
      heterozygous for UNC13D mutation: c. 1232 G>A, and AP3B1 mutation: c. 1075 A>G,
      which were predicted to be pathogenic. Unfortunately, at the time, molecular
      confirmation results for HLH were obtained, and this patient had died from
      progressive HLH disease with multiple organ dysfunction syndrome caused by shock.
      FHL should be considered in the differential diagnosis of adults who present with
      adult-onset still's disease-like symptoms.

PMID- 25980905
TI  - Gaze holding deficits discriminate early from late onset cerebellar degeneration.
AB  - The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem
      neural velocity-to-position integrator to provide stable gaze holding. In healthy
      humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles,
      with a non-linear relationship between eye-drift velocity and eye eccentricity.
      In cerebellar degeneration this calibration is impaired, resulting in
      pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased
      eye drift may be present at any gaze angle (reflecting pure scaling of eye drift
      found in controls) or restricted to far-lateral gaze (reflecting changes in shape
      of the non-linear relationship) and resulting eyed-drift patterns could be
      related to specific disorders. We recorded horizontal eye positions in 21
      patients with cerebellar neurodegeneration (gaze-angle = +/-40 degrees ) and
      clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift
      were determined. MR-images were assessed for cerebellar atrophy. In our patients,
      the relation between eye-drift velocity and gaze eccentricity was non-linear,
      yielding (compared to controls) significant GEN at gaze-eccentricities >=20
      degrees . Pure scaling was most frequently observed (n = 10/18), followed by pure
      shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing
      patients were significantly (p = 0.001) younger at disease-onset compared to pure
      scaling patients. Atrophy centered around the superior/dorsal vermis,
      flocculus/paraflocculus and dentate nucleus and did not correlate with the
      specific drift behaviors observed. Eye drift in cerebellar degeneration varies in
      magnitude; however, it retains its non-linear properties. With different drift
      patterns being linked to age at disease-onset, we propose that the gaze-holding
      pattern (scaling vs. shape-changing) may discriminate early- from late-onset
      cerebellar degeneration. Whether this allows a distinction among specific
      cerebellar disorders remains to be determined. 

PMID- 25980906
TI  - Neuroimaging evidence of gray and white matter damage and clinical correlates in
      progressive supranuclear palsy.
AB  - To evaluate gray matter (GM) and white matter (WM) abnormalities and their
      clinical correlates in patients with progressive supranuclear palsy (PSP).
      Sixteen PSP patients and sixteen age-matched healthy subjects underwent a
      clinical evaluation and multimodal magnetic resonance imaging, including three
      dimensional T1-weighted imaging and diffusion tensor imaging (DTI). Volumetric
      and DTI analyses were computed using SPM and FSL tools. PSP patients showed GM
      volume decrease, involving the frontal cortex, putamen, pallidum, thalamus and
      accumbens nucleus, cerebellum, and brainstem. Additionally, they had widespread
      changes in WM bundles, mainly affecting cerebellar peduncles, thalamic
      radiations, corticospinal tracts, corpus callosum, and longitudinal fasciculi. GM
      volumes did not correlate with WM abnormalities. DTI indices of WM damage, but
      not GM volumes, correlated with clinical scores of disease severity and cognitive
      impairment. The neurodegenerative changes that occur in PSP involve both GM and
      WM structures and develop concurrently though independently. WM damage in PSP
      correlates with clinical scores of disease severity and cognitive impairment,
      thus providing further insight into the pathophysiology of the disease. 

PMID- 25980907
TI  - Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a
      referral center in Kumamoto University from 1997 to 2014.
AB  - This study elucidates the genotypic and phenotypic spectrum and histopathological
      findings related to cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) in Japan. For this single-center
      retrospective observational study, we enrolled 215 patients who were clinically
      suspected of having CADASIL and were examined at Kumamoto University from 1997 to
      2014, and we diagnosed CADASIL in 70 patients. We found 19 different NOTCH3
      mutations in the patients, with the NOTCH3 Arg133Cys mutation being found most
      frequently. We also found the Arg75Pro mutation, a cysteine-sparing NOTCH3
      mutation. CADASIL patients with this Arg75Pro mutation were frequently found
      throughout Japan, and fewer patients with the Arg75Pro mutation showed MRI
      hyperintensity in the anterior temporal pole compared with patients with other
      NOTCH3 mutations. Significantly more CADASIL patients with the NOTCH3 Arg133Cys
      mutation had hyperintensity in the external capsule compared with CADASIL
      patients with the other mutations not including the NOTCH3 Arg75Pro mutation. We
      also showed postmortem pathological findings of the first Japanese CADASIL case
      with the NOTCH3 Arg133Cys mutation, and histopathological findings of fresh
      frozen skin biopsy specimens of CADASIL patients. In conclusions, the spectrum of
      NOTCH3 mutations in Japanese CADASIL patients may be partially explained by
      founder effects. Genotype-phenotype correlations may exist in CADASIL, which
      should be considered so as to make an accurate diagnosis of CADASIL in each
      population. Fresh frozen skin biopsy specimens may aid detection of Notch3
      deposits on vascular walls for an improved diagnosis of CADASIL. 

PMID- 25980908
TI  - Tetrazole activity against Candida albicans. The role of KEX2 mutations in the
      sensitivity to (+/-)-1-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propan-2-yl acetate.
AB  - Series of 4-(5-aryl-2H-tetrazol-2-yl)butan-2-ol, 1-(5-aryl-2H-tetrazol-2
      yl)propan-2-ol and their acetates have been screened against Candida albicans.
      Among the tested compounds, (+/-)-1-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propan-2
      yl acetate (E5) proved to be the most effective inhibitor of fungal growth and
      was further evaluated against young (adhesion phase) and mature biofilm in vitro.
      The activity exhibited by the tested tetrazole derivatives against C. albicans
      associated with minor cytotoxicity towards Vero epithelial cells make us suggest
      that E5 could be a promising structure in the development of new antifungals.
      Serine protease Kex2 appeared essential for the resistance mechanism. Further
      investigations of in vivo activity, drug interactions, and E5 structure
      optimization are needed. 

PMID- 25980909
TI  - Compounds from the insect Blaps japanensis with COX-1 and COX-2 inhibitory
      activities.
AB  - Blapsols A-D (1-4), four new compounds possessing a 2,3
      dihydrobenzo[b][1,4]dioxin group, together with five known N-acetyldopamine
      dimers (5-9), were isolated from Blaps japanensis. Their structures including the
      absolute configuration of (+)-1 were determined by means of spectroscopic and X
      ray crystallographic methods. Chiral HPLC was used to separate (-)- and (+)
      enantiomers of compounds 1-4, which were isolated from this insect as racemic
      mixtures. All the compounds were found to have inhibitory effects towards COX-2
      with IC50 values in the range of 1.3-17.8MUM. 

PMID- 25980910
TI  - Assessing the oral bioavailability of difluorosialic acid prodrugs, potent viral
      neuraminidase inhibitors, using a snapshot PK screening assay.
AB  - Difluorosialic acids (DFSAs) are potent inhibitors of viral neuraminidase that
      demonstrate activity against oseltamivir- and zanamivir-resistant strains of
      influenza. Unfortunately, low oral bioavailability precludes their development as
      second generation neuraminidase inhibitors for treating influenza as this leaves
      them unsuitable for use in an oral formulation. Herein is described the
      preparation of a series of DFSA prodrugs designed to increase oral
      bioavailability. These prodrugs were evaluated using a snapshot PK screen and
      stability tests, with successful candidates being further assessed with a full
      pharmacokinetic workup. These new prodrugs increased oral bioavailability by up
      to three times that seen for the parent DFSAs. 

PMID- 25980911
TI  - Enrichment of O-GlcNAc-modified peptides using novel thiol-alkyne and thiol
      disulfide exchange.
AB  - We have developed a selective method for the enrichment of O-linked beta-N
      acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized
      thiol-alkyne and a thiol-disulfide exchange. First, O-GlcNAc-modified peptides
      were enzymatically labeled with an azide-containing GalNAc analog. Then, the
      azide moiety was reacted with thiol-alkyne through a copper(I)-catalyzed azide
      alkyne cycloaddition. The thiol-modified peptides were enriched with thiol
      reactive resin through a thiol-disulfide exchange. At least 500fmol of O-GlcNAc
      modified peptides was selectively isolated from alpha-crystallin tryptic peptides
      and detected by mass spectrometry. This novel enrichment strategy could be used
      for O-GlcNAcome analysis of biological samples. 

PMID- 25980913
TI  - Allobetulin derived seco-oleananedicarboxylates act as inhibitors of
      acetylcholinesterase.
AB  - Ring opening of allobetulone gave either seco-acid 8 or di-acid 4. These acids
      were converted into esters that were screened by Ellman's assay. A dibutenylester
      of low cytotoxicity (NIH 3T3 murine embryonic fibroblasts) was shown to be a good
      mixed-type inhibitor (Ki=3.39, Ki'=2.26MUM) for acetylcholinesterase. 

PMID- 25980912
TI  - Design of selective PI3Kalpha inhibitors starting from a promiscuous pan kinase
      scaffold.
AB  - Starting from compound 1, a potent PI3Kalpha inhibitor having poor general kinase
      selectivity, we used structural data and modelling to identify key exploitable
      differences between PI3Kalpha and the other kinases. This approach led us to
      design chemical modifications of the central pyrazole, which solved the poor
      kinase selectivity seen as a strong liability for the initial compound 1. Amongst
      the modifications explored, a 1,3,4-triazole ring (as in compound 4) as a
      replacement of the initial pyrazole provided good potency against PI3Kalpha, with
      excellent kinase selectivity. 

PMID- 25980914
TI  - An overview on limitations of TiO2-based particles for photocatalytic degradation
      of organic pollutants and the corresponding countermeasures.
AB  - The pollutants classified as "persistent organic pollutants (POPs)", are being
      subject to high concern among the scientific community due to their persistence
      in the environment. TiO2-based photocatalytic process has shown a great potential
      as a low-cost, environmentally friendly and sustainable treatment technology to
      remove POPs in sewage to overcome the shortcomings of the conventional
      technologies. However, this technology suffers from some main technical barriers
      that impede its commercialization, i.e., the inefficient exploitation of visible
      light, low adsorption capacity for hydrophobic contaminants, uniform distribution
      in aqueous suspension and post-recovery of the TiO2 particles after water
      treatment. To improve the photocatalytic efficiency of TiO2, many studies have
      been carried out with the aim of eliminating the limitations mentioned above.
      This review summarizes the recently developed countermeasures for improving the
      performance of TiO2-based photocatalytic degradation of organic pollutants with
      respect to the visible-light photocatalytic activity, adsorption capacity,
      stability and separability. The performance of various TiO2-based photocatalytic
      processes for POPs degradation and the underlying mechanisms were summarized and
      discussed. The future research needs for TiO2-based technology are suggested
      accordingly. This review will significantly improve our understanding of the
      process of photocatalytic degradation of POPs by TiO2-based particles and provide
      useful information to scientists and engineers who work in this field. 

PMID- 25980915
TI  - Rapid and successful start-up of anammox process by immobilizing the minimal
      quantity of biomass in PVA-SA gel beads.
AB  - Rapid start-up of anaerobic ammonium oxidation (anammox) process in up-flow
      column reactors was successfully achieved by immobilizing minimal quantity of
      biomass in polyvinyl alcohol (PVA)-sodium alginate (SA) gel beads. The changes in
      the reactor performance (i.e., nitrogen removal rate; NRR) were monitored with
      time. The results demonstrate that the reactor containing the immobilized biomass
      concentration of 0.33 g-VSS L(-1) achieved NRR of 10.8 kg-N m(-3) d(-1) after 35
      day operation, whereas the reactor containing the granular biomass of 2.5 g-VSS
      L(-1) could achieve only NRR of 3.5 kg-N m(-3) d(-1). This indicates that the gel
      immobilization method requires much lower seeding biomass for start-up of anammox
      reactor. To explain the better performance of the immobilized biomass, the
      biological and physicochemical properties of the immobilized biomass were
      characterized and compared with the naturally aggregated granular biomass.
      Effective diffusion coefficient (De) in the immobilized biomass was directly
      determined by microelectrodes and found to be three times higher than one in the
      granular biomass. High anammox activity (i.e., NH4(+) and NO2(-) consumption
      rates) was evenly detected throughout the gel beads by microelectrodes due to
      faster and deeper substrate transport. In contrast, anammox activity was
      localized in the outer layers of the granular biomass, indicating that the inner
      biomass could not contribute to the nitrogen removal. This difference was in good
      agreement with the spatial distribution of microbes analysed by fluorescence in
      situ hybridization (FISH). Based on these results, PVA-SA gel immobilization is
      an efficient strategy to initiate anammox reactors with minimal quantity of
      anammox biomass. 

PMID- 25980916
TI  - An Abrupt Transformation of Phobic Behavior After a Post-Retrieval Amnesic Agent.
AB  - BACKGROUND: Although disrupting the process of memory reconsolidation has a great
      potential for clinical practice, the fear-amnesic effects are typically
      demonstrated through Pavlovian conditioning. Given that older and stronger
      memories are generally more resistant to change, we tested whether disrupting
      reconsolidation would also diminish fear in individuals who had developed a
      persistent spider fear outside the laboratory. METHODS: Spider-fearful
      participants received a single dose of 40 mg of the noradrenergic beta-blocker
      propranolol (n = 15), double-blind and placebo-controlled (n = 15), after a short
      2-min exposure to a tarantula. To test whether memory reactivation was necessary
      to observe a fear-reducing effect, one additional group of spider-fearful
      participants (n = 15) received a single dose of 40 mg propranolol without memory
      reactivation. RESULTS: Disrupting reconsolidation of fear memory transformed
      avoidance behavior into approach behavior in a virtual binary fashion-an effect
      that persisted at least 1 year after treatment. Interestingly the beta-adrenergic
      drug did initially not affect the self-declared fear of spiders but instead these
      reports followed the instant behavioral transformation several months later.
      CONCLUSIONS: Our findings are in sharp contrast with the currently
      pharmacological and cognitive behavioral treatments for anxiety and related
      disorders. The beta-adrenergic blocker was only effective when the drug was
      administered upon memory reactivation, and a modification in cognitive
      representations was not necessary to observe a change in fear behavior. A new
      wave of treatments that pharmacologically target the synaptic plasticity
      underlying learning and memory seems to be within reach.

PMID- 25980917
TI  - Older drivers' risks of at-fault motor vehicle collisions.
AB  - In aging societies, increasing numbers of older drivers are involved in motor
      vehicle collisions (MVCs), and preserving their safety is a growing concern. In
      this study, we focused on whether older drivers were more likely to cause MVCs
      and injuries than drivers in other age groups. To do so we compared at-fault MVC
      incidence and resulting injury risks by drivers' ages, using data from Japan, a
      country with a rapidly aging population. The at-fault MVC incidence was
      calculated based on distance traveled made for non-commercial purposes, and the
      injury risks posed to at-fault drivers and other road users per at-fault MVCs. We
      used MVC data for 2010 from the National Police Agency of Japan and driving
      exposure data from the Nationwide Person Trip Survey conducted by a Japanese
      governmental ministry in 2010. The at-fault MVC incidence showed a U-shaped curve
      across the drivers' ages, where teenage and the oldest drivers appeared to be the
      highest risk groups in terms of causing MVCs, and the incidence was higher for
      female drivers after age 25. The injury risk older drivers posed to other vehicle
      occupants because of their at-fault MVCs was lower than for drivers in other age
      groups, while their own injury risk appeared much higher. As the number of older
      drivers is increasing, efforts to reduce their at-fault MVCs appear justified. 

PMID- 25980918
TI  - Acceptance of drinking and driving and alcohol-involved driving crashes in
      California.
AB  - BACKGROUND: Alcohol-impaired driving accounts for substantial proportion of
      traffic-related fatalities in the U.S. Risk perceptions for drinking and driving
      have been associated with various measures of drinking and driving behavior. In
      an effort to understand how to intervene and to better understand how risk
      perceptions may be shaped, this study explored whether an objective environmental
      level measure (proportion of alcohol-involved driving crashes in one's
      residential city) were related to individual-level perceptions and behavior.
      METHODS: Using data from a 2012 cross-sectional roadside survey of 1147 weekend
      nighttime drivers in California, individual-level self-reported acceptance of
      drinking and driving and past-year drinking and driving were merged with traffic
      crash data using respondent ZIP codes. Population average logistic regression
      modeling was conducted for the odds of acceptance of drinking and driving and
      self-reported, past-year drinking and driving. RESULTS: A non-linear relationship
      between city-level alcohol-involved traffic crashes and individual-level
      acceptance of drinking and driving was found. Acceptance of drinking and driving
      did not mediate the relationship between the proportion of alcohol-involved
      traffic crashes and self-reported drinking and driving behavior. However, it was
      directly related to behavior among those most likely to drink outside the home.
      DISCUSSION: The present study surveys a particularly relevant population and is
      one of few drinking and driving studies to evaluate the relationship between an
      objective environmental-level crash risk measure and individual-level risk
      perceptions. In communities with both low and high proportions of alcohol
      involved traffic crashes there was low acceptance of drinking and driving. This
      may mean that in communities with low proportions of crashes, citizens have less
      permissive norms around drinking and driving, whereas in communities with a high
      proportion of crashes, the incidence of these crashes may serve as an
      environmental cue which informs drinking and driving perceptions. Perceptual
      information on traffic safety can be used to identify places where people may be
      at greater risk for drinking and driving. Community-level traffic fatalities may
      be a salient cue for tailoring risk communication.

PMID- 25980919
TI  - Balancing omega-6 and omega-3 fatty acids in ready-to-use therapeutic foods
      (RUTF).
AB  - Ready-to-use therapeutic foods (RUTFs) are a key component of a life-saving
      treatment for young children who present with uncomplicated severe acute
      malnutrition in resource limited settings. Increasing recognition of the role of
      balanced dietary omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in
      neurocognitive and immune development led two independent groups to evaluate
      RUTFs. Jones et al. (BMC Med 13:93, 2015), in a study in BMC Medicine, and Hsieh
      et al. (J Pediatr Gastroenterol Nutr 2015), in a study in the Journal of
      Pediatric Gastroenterology and Nutrition, reformulated RUTFs with altered PUFA
      content and looked at the effects on circulating omega-3 docosahexaenoic acid
      (DHA) status as a measure of overall omega-3 status. Supplemental oral
      administration of omega-3 DHA or reduction of RUTF omega-6 linoleic acid using
      high oleic peanuts improved DHA status, whereas increasing omega-3 alpha
      linolenic acid in RUTF did not. The results of these two small studies are
      consistent with well-established effects in animal studies and highlight the need
      for basic and operational research to improve fat composition in support of omega
      3-specific development in young children as RUTF use expands.

PMID- 25980920
TI  - The Apex of the Deep Cartilage: A Landmark and New Technique to Help Identify
      Femoral Tunnel Placement in Anterior Cruciate Ligament Reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the apex of the deep cartilage
      (ADC) as a landmark to help guide femoral tunnel placement during anatomic single
      bundle anterior cruciate ligament (ACL) reconstruction. Our secondary purpose was
      to assess whether or not the endoscopic transtibial femoral offset drill guide
      could reach the center of the ACL's femoral footprint. METHODS: Eight formalin
      injected cadaveric knees were dissected and the center of the ACL femoral
      footprints identified. The ADC was selected as an easily identifiable landmark
      during arthroscopy and was used to reference the position of the ACL femoral
      footprint with the knee flexed at 90 degrees . Next, a 7-mm transtibial femoral
      ACL drill guide was used to engage the posterior aspect of the lateral condyle at
      the level of the femoral footprint. This position was marked, and the distance
      from the center of the femoral footprint was recorded for each specimen.
      Descriptive statistics were used to report our measurements. RESULTS: The median
      high and shallow measurements were 3 mm (range, 1 to 4 mm) and 12 mm (range, 11
      to 17 mm), respectively. The femoral offset guide never reached the center of the
      femoral footprint in all specimens; the median distance between the 2
      measurements was 4.5 mm (range, 2 to 9 mm). CONCLUSIONS: If the anatomy is
      difficult to delineate at the time of reconstruction, our study suggests using
      the ADC as a landmark to guide anatomic placement. The dissection of 8 cadavers
      showed that the center of the ACL femoral footprint had a median position of 3 mm
      high and 12 mm shallow to the ADC. We also showed that the transtibial femoral
      offset guide did not reach the center of the ACL footprint on all specimens and
      should therefore not be used for anatomic ACL reconstruction. CLINICAL RELEVANCE:
      Current commercially available transtibial femoral offset guides cannot reach the
      center of the ACL's femoral footprint and therefore should not be used.
      Alternative techniques, such as referencing from the ADC through an anteromedial
      (AM) portal, are recommended.

PMID- 25980921
TI  - Demographic Trends and Complication Rates in Arthroscopic Elbow Surgery.
AB  - PURPOSE: To investigate demographic trends in elbow arthroscopy over time, as
      well as to query complication rates requiring reoperation associated with these
      procedures. METHODS: The Current Procedural Terminology (CPT) billing codes of
      patients undergoing elbow arthroscopy were searched using a national insurance
      database. From the years 2007 to 2011, over 20 million orthopaedic patient
      records were present in the database with an orthopaedic International
      Classification of Diseases, Ninth Revision diagnosis code or CPT code. Our search
      for procedures and the corresponding CPT codes for the elbow included diagnostic
      arthroscopy, loose body removal, synovectomy, and debridement. The type of
      procedure, date, gender, and region of the country were identified for each
      patient. In addition, the incidence of reoperation for infection, stiffness, and
      nerve injury was examined. RESULTS: There was a significant increase in
      arthroscopic elbow procedures over the study period. Male patients accounted for
      71% of patients undergoing these procedures. Of the elbow arthroscopy patients,
      22% were aged younger than 20 years, 25% were aged 20 to 39 years, 47% were aged
      40 to 59 years, and 6% were aged 60 years or older. Other than synovectomy, there
      were regional variations in the incidence of each procedure type. The overall
      rate of reoperation was 2.2%, with specific rates of 0.26% for infection, 0.63%
      for stiffness, and 1.26% for nerve injury. It should be noted that because only
      the complications requiring reoperation are recorded in the database, these
      numbers are lower than the overall complication rate. CONCLUSIONS: Overall, the
      incidence of elbow arthroscopy in this patient population is relatively low and
      appears to be increasing slightly over time. In the database used in this study,
      elbow arthroscopy procedures were most commonly performed in male patients and in
      patients aged 40 to 59 years, with regional variation in the incidence of the
      different procedures. Furthermore, the rate of complications requiring
      reoperation was low, with a nerve operation being the most common reoperation
      performed. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 25980922
TI  - Comparison of 3-Dimensional Computed Tomography-Based Measurement of Glenoid Bone
      Loss With Arthroscopic Defect Size Estimation in Patients With Anterior Shoulder
      Instability.
AB  - PURPOSE: The purpose of this study was to compare four 3-dimensional (3D)
      computed tomography (CT) methods of measuring glenoid bone loss with the
      arthroscopic estimation of glenoid bone loss. METHODS: Twenty patients with
      recurrent anterior shoulder instability underwent bilateral shoulder CT scans and
      were found to have glenoid bone loss. Arthroscopic estimation of glenoid bone
      loss was performed in all patients. Three-dimensional CT reconstruction was
      performed on the CT scans of each patient. The glenoid bone loss of each patient
      was measured using the surface area, Pico, ratio, and anteroposterior distance
      from-bare area methods. The mean percent loss calculated with each method was
      compared with arthroscopy to determine the reliability of arthroscopy in the
      measurement of glenoid bone loss. RESULTS: The mean percent bone loss calculated
      with arthroscopic estimation, surface area, Pico, ratio, and anteroposterior
      distance-from-bare area methods was 18.13% +/- 11.81%, 12.15% +/- 8.50% (P =
      .005), 12.77% +/- 8.17% (P = .002), 9.50% +/- 8.74% (P < .001), and 12.44% +/-
      10.68% (P = .001), respectively. Repeated-measures analysis of variance showed
      that the 3D CT methods and arthroscopy were significantly different (F4,76 =
      13.168, P = .02). The estimate using arthroscopy is 55% greater than the average
      of the 3D CT methods. CONCLUSIONS: Our findings suggest that arthroscopy
      significantly overestimates glenoid bone loss compared with CT and call into
      question its validity as a method of measurement. A more internally consistent
      and accurate method for the measurement of glenoid bone loss is necessary to
      appropriately diagnose and treat shoulder instability. LEVEL OF EVIDENCE: Level
      IV, case series.

PMID- 25980923
TI  - Platelet-Rich Plasma Augmentation of Arthroscopic Hip Surgery for
      Femoroacetabular Impingement: A Prospective Study With 24-Month Follow-up.
AB  - PURPOSE: The objective of this study is to evaluate the clinical and immunologic
      effects of intra-articular doses of platelet-rich plasma (PRP) in arthroscopic
      hip surgery for femoroacetabular impingement. METHODS: Preoperatively, patients
      were randomized either to receive an intra-articular injection of PRP (group I, n
      = 30) or not to receive PRP (group II, n = 27) at the end of hip arthroscopic
      surgery. To evaluate the clinical outcome and follow-up, we used the modified
      Harris Hip Score (mHHS) 3, 6, and 24 months after surgery. Pain was evaluated
      using a visual analog scale 24 hours, 48 hours, 3 months, and 6 months after
      surgery. The radiologic outcome was analyzed using radiographs and magnetic
      resonance imaging (MRI) obtained before surgery and 6 months after surgery.
      Labral integration and joint effusion were evaluated with MRI at 6 months. For
      statistical analysis, an independent t test and the Wilcoxon rank sum test were
      used (P < .05 was considered statistically significant). RESULTS: The visual
      analog scale score 48 hours after surgery was 3.04 in group I compared with 5.28
      in group II (P < .05). At the 3-month follow-up, the mHHS was 91.79 in group I
      versus 90.97 in group II (P = .65). At the 24-month follow-up, the mHHS was 93.41
      in group I (P = .56) versus 92.32 in group II (P = .52). At the 6-month follow
      up, MRI showed no effusion in 36.7% of patients in group I versus 21.1% of
      patients in group II (P = .013). Regarding labral integration, no statistical
      differences were observed between the groups (P = .76). CONCLUSIONS: In this
      randomized study, PRP resulted in lower postoperative pain scores at 48 hours and
      fewer joint effusions at 6 months. These findings suggest that PRP may have a
      benefit regarding postoperative inflammation; however, the long-term clinical
      benefit is unclear. LEVEL OF EVIDENCE: Level II, lesser-quality randomized
      controlled trial.

PMID- 25980924
TI  - Knowledge management in the QbD paradigm: manufacturing of biotech therapeutics.
AB  - In the quality by design (QbD) paradigm, global regulatory agencies have
      introduced the concepts of quality risk management and knowledge management (KM)
      as enablers for an enhanced pharmaceutical quality system. Although the concept
      of quality risk management has been well elucidated in the literature, the topic
      of KM has received relatively scant attention. In this paper we present an
      opinion on KM in the QbD paradigm as it relates to the manufacturing of biotech
      therapeutic products. Both academic and industrial viewpoints have been
      considered and key gaps have been elucidated. The authors conclude that there is
      an urgent need for the biotech industry to create efficient KM approaches if they
      wish to be successful in QbD implementation. 

PMID- 25980925
TI  - In-vivo iMap IVUS comparison of in-stent neointima and native coronary
      atherosclerosis.
AB  - PURPOSE: The purpose of this study was to compare plaque characteristics of
      native coronary atherosclerosis and in-stent neointima ten months after ST
      elevation myocardial infarction (STEMI) using iMap intravascular ultrasound
      (IVUS). METHODS: In 49 patients in-stent neointima and the coronary segment
      proximal to the stent were analyzed with iMap intravascular ultrasound (IVUS) ten
      months after primary PCI for STEMI. RESULTS: A higher percentage of necrotic
      tissue was observed in the proximal coronary segment compared to the in-stent
      neointima by iMap IVUS (25.5% +/- 12.8% vs 12.3% +/- 3.3%, p < 0.0001) ten months
      after STEMI. The proportion of fibrotic tissue in the proximal segment was lower
      (63.6% +/- 14.8% vs 72.0% +/- 5.7%, p = 0.002) and the proportion of the lipidic
      tissue was higher (8.8% +/- 3.0% vs 5.9% +/- 2.0%, p < 0.0001) than in-stent
      neointima. CONCLUSIONS: In patients ten months after STEMI, in-stent neointima
      contained a higher proportion of fibrotic tissue and lower proportion of necrotic
      and lipidic tissue compared the native atherosclerotic lesion.

PMID- 25980927
TI  - Different space preferences and within-host competition promote niche
      partitioning between symbiotic feather mite species.
AB  - Obligate symbionts (including parasites, commensals and mutualists) often share
      host species and host-based food resources. Such symbionts are frequently
      distributed unequally among hosts with different phenotypic features, or occupy
      different regions on a host. However, the processes leading to distinct within
      host symbiont distributions remain obscure. We aimed to test whether distinct in
      host symbiont distributions arise as the outcome of species-specific habitat
      preferences or interspecific competition, and how host phenotype influences such
      processes. To this end, we studied the distribution within and among individual
      bird hosts of two feather mites (Proctophyllodes sylviae and Trouessartia
      bifurcata) of migratory and sedentary European blackcaps, Sylvia atricapilla,
      wintering in sympatry. Trouessartia bifurcata was mostly restricted to resident
      blackcaps, while P. sylviae was abundant on both host types. Within hosts, each
      species tended to settle on different feather sectors (proximal or distal,
      respectively), which they filled by spreading on the wing following ordered but
      opposite patterns, thereby supporting the view that spatial segregation was
      primarily the outcome of dissimilar space preferences. However, we also found
      evidence of competition finely tuning mite distributions: when P. sylviae
      increased abundance and expanded onto the range of T. bifurcata, abundances of
      the two species were negatively correlated in the shared areas. In addition, the
      presence of T. bifurcata on a host was associated with a more restricted
      distribution of P. sylviae. Our results show that both species-specific
      preferences and interspecific interactions contribute to shaping mite
      distributions among and on individual hosts, a situation likely mirrored by other
      host-multi-symbiont systems. 

PMID- 25980928
TI  - Liver transplantation after endoscopic ultrasound-guided cholecystoduodenostomy
      for acute cholecystitis: A note of caution.

PMID- 25980926
TI  - Innate inflammation in type 1 diabetes.
AB  - Type 1 diabetes mellitus (T1D) is an autoimmune disease often diagnosed in
      childhood that results in pancreatic beta-cell destruction and life-long insulin
      dependence. T1D susceptibility involves a complex interplay between genetic and
      environmental factors and has historically been attributed to adaptive immunity,
      although there is now increasing evidence for a role of innate inflammation.
      Here, we review studies that define a heightened age-dependent innate
      inflammatory state in T1D families that is paralleled with high fidelity by the
      T1D-susceptible biobreeding rat. Innate inflammation may be driven by changes in
      interactions between the host and environment, such as through an altered
      microbiome, intestinal hyperpermeability, or viral exposures. Special focus is
      put on the temporal measurement of plasma-induced transcriptional signatures of
      recent-onset T1D patients and their siblings as well as in the biobreeding rat as
      it defines the natural history of innate inflammation. These sensitive and
      comprehensive analyses have also revealed that those who successfully managed T1D
      risk develop an age-dependent immunoregulatory state, providing a possible
      mechanism for the juvenile nature of T1D. Therapeutic targeting of innate
      inflammation has been proven effective in preventing and delaying T1D in rat
      models. Clinical trials of agents that suppress innate inflammation have had more
      modest success, but efficacy may be improved by the addition of combinatorial
      approaches that target other aspects of T1D pathogenesis. An understanding of
      innate inflammation and mechanisms by which this susceptibility is both
      potentiated and mitigated offers important insight into T1D progression and
      avenues for therapeutic intervention.

PMID- 25980929
TI  - [Evaluation of the theoretical teaching of postgraduate medical students in
      France].
AB  - OBJECTIVES: In France, medical students regularly complain about the shortcomings
      of their theoretical training and the necessity of its adaptation to better fit
      the needs of students. The goal was to evaluate the theoretical teaching
      practices in postgraduate medical studies by: 1) collecting data from medical
      students in different medical faculties in France; 2) comparing this data with
      expected practices when it is possible; 3) and proposing several lines of
      improvement. METHODS: A survey of theoretical practices in the 3rd cycle of
      medical studies was conducted by self-administered questionnaires which were free
      of charge, anonymous, and administered electronically from July 3 to October 31,
      2013 to all medical students in France. RESULTS: National, inter-regional,
      regional and field internship educational content was absent in respectively
      50.5%, 42.8%, 26.0% and 30.2% of cases. Medical students follow complementary
      training due to insufficient DES and/or DESC 2 training in 43.7% of cases or as
      part of a professional project in 54.9% of cases. The knowledge sought by medical
      students concerns the following crosscutting topics: career development (58.9%),
      practice management (50.7%), medical English (50.4%) and their specialty
      organization (49.9%). Fifty-four point one percent would like to be evaluated on
      their theoretical training on an annual basis. CONCLUSION: The results of this
      first national survey give insights into the theoretical teaching conditions in
      postgraduate medical education in France and the aspirations of medical students.

PMID- 25980930
TI  - Sensitivity of mGROWA-simulated groundwater recharge to changes in soil and land
      use parameters in a Mediterranean environment and conclusions in view of ensemble
      based climate impact simulations.
AB  - This study examines the impact of changing climatic conditions on groundwater
      recharge in the Riu Mannu catchment in southern Sardinia. Based on an ensemble of
      four downscaled and bias corrected combinations of Global and Regional Climate
      Models (GCM-RCMs), the deterministic distributed water balance model mGROWA was
      used to simulate long-term mean annual groundwater recharge in the catchment for
      four 30-year periods between 1981 and 2100. The four employed GCM-RCM
      combinations project an adverse climatic development for the study area: by the
      period 2071-2100, annual rainfall will decrease considerably, while grass
      reference evapotranspiration will rise. Accordingly, ensemble results for our
      base scenario showed a climate-induced decrease in the median of annual
      groundwater recharge in areas covered by Macchia from 42-48mm/a to 25-35mm/a
      between the periods 1981-2010 and 2071-2100, corresponding to a reduction of 17
      43%. To take into account the influence of additional plant available water
      storage in weathered bedrock on groundwater recharge generation, the model was
      extended by a regolith zone for regions covered by Mediterranean Macchia. In a
      set of model runs ("scenarios"), parameter values controlling the water storage
      capacity of this zone were increased step-wise and evaluated by comparison to the
      base scenario to analyze the sensitivity of the model outcome to these changes.
      The implementation of a regolith zone had a considerable impact on groundwater
      recharge and resulted in a decrease of the median in annual groundwater recharge:
      by 2071-2100, the 35% scenario (available water content in the regolith of 3.9 to
      5.7vol.%) showed a reduction of 67-82% as compared to the period 1981-2010 in the
      base scenario. In addition, we also examined the influence of changes in the crop
      coefficients (Kc) as well as different soil texture distributions on simulated
      groundwater recharge. 

PMID- 25980931
TI  - Circulating tumor cells in prostate cancer: Does (nuclear) size matter?

PMID- 25980932
TI  - Ribonuclease like 5 regulates zebrafish yolk extension by suppressing a p53
      dependent DNA damage response pathway.
AB  - Ribonuclease like 5 (Rnasel5) is a novel member of the zebrafish ribonuclease A
      family and its expression is increased during early embryogenesis. However, the
      in vivo biological function of Rnasel5 remains to be elucidated. Here, we report
      that knockdown of Rnasel5 by morhpolinos caused shrunken yolk extension as well
      as increased DNA damage at yolk syncytial layer and external tissue layers via
      the activation of p53 pathway. In addition, the morphological defects caused by
      Rnasel5 knockdown can be partially rescued by mRNA injection. Our findings
      provide the first functional characterization of Rnasel5 in zebrafish development
      and reveal its critical role in yolk extension by modulation of the p53 pathway. 

PMID- 25980934
TI  - MicroRNAs and their potential therapeutic applications in neural tissue
      engineering.
AB  - The inherent poor regeneration capacity of nerve tissues, especially in the
      central nervous system, poses a grand challenge for neural tissue engineering.
      After injuries, the local microenvironment often contains potent inhibitory
      molecules and glial scars, which do not actively support axonal regrowth.
      MicroRNAs can direct fate of neural cells and are tightly controlled during nerve
      development. Thus, RNA interference using microRNAs is a promising method to
      enhance nerve regeneration. Although the physiological roles of microRNA
      expression levels in various cellular activities or disease conditions have been
      extensively investigated, the translational use of these understanding for neural
      tissue engineering remains limited. This review aims to highlight essential
      microRNAs that participate in cellular behaviors within the adult nervous system
      and their potential therapeutic applications. In addition, possible delivery
      methods are also suggested for effective gene silencing in neural tissue
      engineering.

PMID- 25980933
TI  - Adaptation of peroxisome proliferator-activated receptor alpha to hibernation in
      bats.
AB  - BACKGROUND: Hibernation is a survival mechanism in the winter for some animals.
      Fat preserved instead of glucose produced is the primary fuel during winter
      hibernation of mammals. Many genes involved in lipid metabolism are regulated by
      the peroxisome proliferator-activated receptor alpha (PPARalpha). The role of
      PPARalpha in hibernation of mammals remains largely unknown. Using a
      multidisciplinary approach, we investigated whether PPARalpha is adapted to
      hibernation in bats. RESULTS: Evolutionary analyses revealed that the omega value
      of Pparalpha of the ancestral lineage of hibernating bats in both
      Yinpterochiroptera and Yangochiroptera was lower than that of non-hibernating
      bats in Yinpterochiroptera, suggesting that a higher selective pressure acts on
      Pparalpha in hibernating bats. PPARalpha expression was found to be increased at
      both mRNA and protein levels in distantly related bats (Rhinolophus ferrumequinum
      and Hipposideros armiger in Yinpterochiroptera and Myotis ricketti in
      Yangochiroptera) during their torpid episodes. Transcription factors such as
      FOXL1, NFYA, NFYB, SP1, TBP, and ERG were bioinformatically determined to have a
      higher binding affinity to the potential regulatory regions of Pparalpha in
      hibernating than in non-hibernating mammals. Genome-wide bioinformatic analyses
      of 64 mammalian species showed that PPARalpha has more potential target genes and
      higher binding affinity to these genes in hibernating than in non-hibernating
      mammals. CONCLUSIONS: We conclude that PPARalpha is adapted to hibernation in
      bats based on the observations that Pparalpha has a more stringent functional
      constraint in the ancestral lineage of hibernating bats and a higher level of
      expression in hibernating than in non-hibernating bats. We also conclude that
      PPARalpha plays a very important role in hibernation as hibernators have more
      PPARalpha target genes than non-hibernators, and PPARalpha in hibernators has a
      higher binding affinity for its target genes than in non-hibernators.

PMID- 25980935
TI  - Enzyme therapeutics for systemic detoxification.
AB  - Life relies on numerous biochemical processes working synergistically and
      correctly. Certain substances disrupt these processes, inducing living organism
      into an abnormal state termed intoxication. Managing intoxication usually
      requires interventions, which is referred as detoxification. Decades of
      development on detoxification reveals the potential of enzymes as ideal
      therapeutics and antidotes, because their high substrate specificity and
      catalytic efficiency are essential for clearing intoxicating substances without
      adverse effects. However, intrinsic shortcomings of enzymes including low
      stability and high immunogenicity are major hurdles, which could be overcome by
      delivering enzymes with specially designed nanocarriers. Extensive investigations
      on protein delivery indicate three types of enzyme-nanocarrier architectures that
      show more promise than others for systemic detoxification, including liposome
      wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes.
      This review highlights recent advances in these nano-architectures and discusses
      their applications in systemic detoxifications. Therapeutic potential of various
      enzymes as well as associated challenges in achieving effective delivery of
      therapeutic enzymes will also be discussed. 

PMID- 25980936
TI  - Exon skipping therapy for Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is caused mostly by internal deletions in the
      gene for dystrophin, a protein essential for maintaining muscle cell membrane
      integrity. These deletions abrogate the reading frame and the lack of dystrophin
      results in progressive muscle deterioration. DMD patients experience progressive
      loss of ambulation, followed by a need for assisted ventilation, and eventual
      death in mid-twenties. By the method of exon skipping in dystrophin pre-mRNA the
      reading frame is restored and the internally deleted but functional dystrophin is
      produced. Two oligonucleotide drugs that induce desired exon skipping are
      currently in advanced clinical trials.

PMID- 25980939
TI  - Three-dimensional cardiac tissue fabrication based on cell sheet technology.
AB  - Cardiac tissue engineering is a promising therapeutic strategy for severe heart
      failure. However, conventional tissue engineering methods by seeding cells into
      biodegradable scaffolds have intrinsic limitations such as inflammatory responses
      and fibrosis arising from the degradation of scaffolds. On the other hand, we
      have developed cell sheet engineering as a scaffold-free approach for cardiac
      tissue engineering. Confluent cultured cells are harvested as an intact cell
      sheet using a temperature-responsive culture surface. By layering cardiac cell
      sheets, it is possible to form electrically communicative three-dimensional
      cardiac constructs. Cell sheet transplantation onto damaged hearts in several
      animal models has revealed improvements in heart functions. Because of the lack
      of vasculature, the thickness of viable cardiac cell sheet-layered tissues is
      limited to three layers. Pre-vascularized structure formation within cardiac
      tissue and multi-step transplantation methods has enabled the formation of thick
      vascularized tissues in vivo. Furthermore, development of original bioreactor
      systems with vascular beds has allowed reconstruction of three-dimensional
      cardiac tissues with a functional vascular structure in vitro. Large-scale
      culture systems to generate pluripotent stem cell-derived cardiac cells can
      create large numbers of cardiac cell sheets. Three-dimensional cardiac tissues
      fabricated by cell sheet engineering may be applied to treat heart disease and
      tissue model construction. 

PMID- 25980940
TI  - Percutaneous Retroperitoneal Splenorenal Shunt for Symptomatic Portal Vein
      Thrombosis After Liver Transplantation.
AB  - Acute or recurrent bleeding from ectopic varices is a potentially life
      threatening condition in rare patients with extrahepatic complete portal vein
      thrombosis (PVT) after liver transplantation (LT). In this setting, the role of
      interventional radiology is very limited and surgical shunts, in particular
      splenorenal shunts are usually used, despite the high associated mortality. We
      present the first reports of the clinical use of a new minimally invasive
      technique, percutaneous retroperitoneal splenorenal shunt (PRESS), in two LT
      recipients with life-threatening variceal hemorrhage secondary to PVT. Both
      patients had a successful PRESS using a transplenic approach with resolution of
      bleeding, avoiding the need for a potentially complicated laparotomy. The PRESS
      procedure is a useful addition to the interventional armamentarium that can be
      used in cases unsuitable for surgical shunt, and refractory to endoscopic
      management. In the future, this technique may be an alternative to surgical
      shunts as the standard procedure in patients with extra-hepatic PVT, just as the
      transjugular intrahepatic portosystemic shunt (TIPS) procedure has become for the
      management of portal hypertension in the absence of PVT. Longer-term follow-up
      will be needed to establish the long-term success of this procedure. 

PMID- 25980937
TI  - MicroRNAs in vascular tissue engineering and post-ischemic neovascularization.
AB  - Increasing numbers of paediatric patients with congenital heart defects are
      surviving to adulthood, albeit with continuing clinical needs. Hence, there is
      still scope for revolutionary new strategies to correct vascular anatomical
      defects. Adult patients are also surviving longer with the adverse consequences
      of ischemic vascular disease, especially after acute coronary syndromes brought
      on by plaque erosion and rupture. Vascular tissue engineering and therapeutic
      angiogenesis provide new hope for these patients. Both approaches have shown
      promise in laboratory studies, but have not yet been able to deliver clear
      evidence of clinical success. More research into biomaterials, molecular medicine
      and cell and molecular therapies is necessary. This review article focuses on the
      new opportunities offered by targeting microRNAs for the improved production and
      greater empowerment of vascular cells for use in vascular tissue engineering or
      for increasing blood perfusion of ischemic tissues by amplifying the resident
      microvascular network. 

PMID- 25980941
TI  - Developmental validation of the ParaDNA((r)) Intelligence System-A novel approach
      to DNA profiling.
AB  - DNA profiling through the analysis of STRs remains one of the most widely used
      tools in human identification across the world. Current laboratory STR analysis
      is slow, costly and requires expert users and interpretation which can lead to
      instances of delayed investigations or non-testing of evidence on budget grounds.
      The ParaDNA((r)) Intelligence System has been designed to provide a simple, fast
      and robust way to profile DNA samples in a lab or field-deployable manner. The
      system analyses 5-STRs plus amelogenin to deliver a DNA profile that enables
      users to gain rapid investigative leads and intelligent prioritisation of samples
      in human identity testing applications. Utilising an innovative sample collector,
      minimal training is required to enable both DNA analysts and nonspecialist
      personnel to analyse biological samples directly, without prior processing, in
      approximately 75min. The test uses direct PCR with fluorescent HyBeacon((r))
      detection of STR allele lengths to provide a DNA profile. The developmental
      validation study described here followed the Scientific Working Group on DNA
      Analysis Methods (SWGDAM) guidelines and tested the sensitivity, reproducibility,
      accuracy, inhibitor tolerance, and performance of the ParaDNA Intelligence System
      on a range of mock evidence items. The data collected demonstrate that the
      ParaDNA Intelligence System displays useful DNA profiles when sampling a variety
      of evidence items including blood, saliva, semen and touch DNA items indicating
      the potential to benefit a number of applications in fields such as forensic,
      military and disaster victim identification (DVI). 

PMID- 25980938
TI  - Human pluripotent stem cells: Prospects and challenges as a source of
      cardiomyocytes for in vitro modeling and cell-based cardiac repair.
AB  - Human pluripotent stem cells (PSCs) represent an attractive source of
      cardiomyocytes with potential applications including disease modeling, drug
      discovery and safety screening, and novel cell-based cardiac therapies. Insights
      from embryology have contributed to the development of efficient, reliable
      methods capable of generating large quantities of human PSC-cardiomyocytes with
      cardiac purities ranging up to 90%. However, for human PSCs to meet their full
      potential, the field must identify methods to generate cardiomyocyte populations
      that are uniform in subtype (e.g. homogeneous ventricular cardiomyocytes) and
      have more mature structural and functional properties. For in vivo applications,
      cardiomyocyte production must be highly scalable and clinical grade, and we will
      need to overcome challenges including graft cell death, immune rejection,
      arrhythmogenesis, and tumorigenic potential. Here we discuss the types of human
      PSCs, commonly used methods to guide their differentiation into cardiomyocytes,
      the phenotype of the resultant cardiomyocytes, and the remaining obstacles to
      their successful translation. 

PMID- 25980943
TI  - Visual and narrative representations of mental health and addiction by law
      enforcement.
AB  - In Vancouver, British Columbia, Canada's third largest city, the Vancouver Police
      Department (VPD), has positioned itself as being at the forefront of mental
      health regulation. The VPD problematization of the "mental health crisis" in
      Vancouver draws on discourses of addiction and dangerousness. This is partially
      achieved by the twinning of mental health with addiction (dual diagnoses) and a
      focus on illegal drug consumption, and is supported through law enforcement's
      role as active claims-makers. Consequently, there is a mobilization of resources
      to identify, discipline, and contain people identified as mentally ill and
      addicted with little examination of both the textual and visual discourses that
      serve this purpose. This article addresses this gap through an analysis of the
      images and discursive framing of people with mental illness and addictions by the
      VPD in two Vancouver Police Department reports published in 2008 and 2009. 

PMID- 25980942
TI  - Apoptosis-induced activation of HIV-1 in latently infected cell lines.
AB  - BACKGROUND: Despite much work, safe and effective approaches to attack and
      deplete the long-lived reservoir of cells latently infected with HIV-1 remain an
      elusive goal. Patients infected with HIV-1 treated with cytotoxic agents or bone
      marrow transplantation can experience decreases in the reservoir of HIV-1
      latently infected cells. Other viruses capable of long-term latency, such as
      herpesviruses, can sense host cell apoptosis and respond by initiating
      replication. These observations suggest that other viruses capable of long-term
      latency, like HIV-1, might also sense when its host cell is about to undergo
      apoptosis and respond by initiating replication. RESULTS: Pro-monocytic (U1) and
      lymphoid (ACH-2) HIV-1 persistently infected cell lines were treated with
      cytotoxic drugs - doxorubicin, etoposide, fludarabine phosphate, or vincristine -
      and activation of latent HIV-1 was evaluated using assays for HIV-1 RNA and p24
      production. Both cell lines showed dose-dependent increases in apoptosis and
      associated HIV-1 activation following exposure to the cytotoxic agents.
      Pretreatment of the cells with the pan-caspase inhibitor Z-VAD-FMK prior to
      exposure to the cytotoxic agents inhibited apoptosis and viral activation. Direct
      exposure of the latently infected cell lines to activated caspases also induced
      viral replication. HIV-1 virions produced in association with host cell apoptosis
      were infectious. CONCLUSIONS: The results indicate that latent HIV-1 can sense
      when its host cell is undergoing apoptosis and responds by completing its
      replication cycle. The results may help explain why patients treated with
      cytotoxic regimens for bone marrow transplantation showed reductions in the
      reservoir of latently infected cells. The results also suggest that the
      mechanisms that HIV-1 uses to sense and respond to host cell apoptosis signals
      may represent helpful new targets for approaches to attack and deplete the long
      lived reservoir of cells latently infected with HIV-1.

PMID- 25980944
TI  - Role of gonadotropin-releasing hormone analogues in metastatic male breast
      cancer: results from a pooled analysis.
AB  - BACKGROUND: Male breast cancer is a rare malignancy. Despite the lack of
      prospectively generated data from trials in either the adjuvant or metastatic
      setting, patients are commonly treated with hormone therapies. Much controversy
      exists over the use of gonadotropin-releasing hormone analogues in metastatic
      male breast cancer patients. We conducted this study to provide more concrete
      ground on the use of gonadotropin-releasing hormone analogues in this setting.
      METHODS: We herein present results from a pooled analysis including 60 metastatic
      male breast cancer patients treated with either an aromatase inhibitor or
      cyproterone acetate as a monotherapy (23 patients) or combined with a
      gonadotropin-releasing hormone analogue (37 patients). RESULTS: Overall response
      rate was 43.5% in patients treated with monotherapy and 51.3% with combination
      therapy (p = 0.6). Survival outcomes favored combination therapy in terms of
      median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year
      progression-free survival rate (43.2% versus 21.7%; p = 0.05), median overall
      survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate
      (64.9% versus 43.5%; p = 0.05). CONCLUSIONS: In metastatic male breast cancer
      patients, the combined use of gonadotropin-releasing hormone analogues and
      aromatase inhibitors or antiandrogens seems to be associated with greater
      efficacy, particularly in terms of survival outcomes, compared with monotherapy.
      Collectively, these results encourage considering these agents in the metastatic
      setting.

PMID- 25980945
TI  - Usefulness of Neutrophil/Lymphocyte Ratio as a Predictor of Atrial Fibrillation:
      A Meta-analysis.
AB  - BACKGROUND AND AIMS: Current evidence suggests that a high neutrophil/lymphocyte
      ratio (NLR) may increase the risk of atrial fibrillation (AF), but this
      association is still uncertain. The aim of the comprehensive meta-analysis was to
      evaluate the potential association between NLR and the risk of AF. METHODS: We
      conducted a systematic literature search using electronic databases (PubMed,
      Ovid, Embase, Cochrane Database and Web of Science) to identify the studies
      reporting the association between NLR and risk of AF. We searched the literature
      published January 2015 or earlier. We used both fixed-effects and random-effects
      models to calculate the overall effect estimate. An I(2) > 50% indicates at least
      moderate statistical heterogeneity. A sensitivity analysis and subgroup analysis
      were performed to find the origin of heterogeneity. RESULTS: We retrieved 11
      studies involving a total of 2,766 participants. The combined odds ratio (OR) of
      incident AF for baseline NLR level was 1.25 (95% confidence interval [CI] 1.16
      1.35) with significant heterogeneity across studies (I(2) = 82.7%, p < 0.01) and
      for the post-NLR level (following CABG, RFCA and cardioversion) was 1.518 (95% CI
      1.076-2.142) with significant heterogeneity across studies (I(2) = 93.7%, p =
      0.017). We also showed an association between AF recurrence following CABG, RFCA
      and cardioversion and baseline NLR level (OR 1.517, 95% CI 1.108-2.079) with
      significant heterogeneity across studies (I(2) = 86.8%, p < 0.01). CONCLUSIONS:
      Our comprehensive meta-analysis suggests that the high level of NLR, whether
      baseline or postsurgery/procedure, is associated with the increased risk of AF
      recurrence/occurrence.

PMID- 25980946
TI  - Omentin Polymorphism and its Relations to Bone Mineral Density in Women.
AB  - BACKGROUND AND AIMS: Recognition of different genetic variants underlying
      development of osteoporosis would make it possible to administer individual
      symptomatic treatment as well as early prophylactics of osteoporosis. The aim of
      the study was to evaluate frequency of polymorphism 326A/T of gene ITLN-1 and
      assessment of its relations with the clinical parameters of osseous turnover and
      degree of postmenopausal osteoporosis. METHODS: The study included 800 women at
      the postmenopausal (505) and reproductive (295) age throughout Wielkopolska
      region in Poland. The postmenopausal group included women with osteoporosis and
      osteopenia and the healthy ones. Women at the reproductive age were healthy.
      Frequency of the tested gene polymorphism was evaluated in the group where BMD
      was marked and in the control group. RESULTS: The analysis of the polymorphism
      A326T of gene ITLN-1 showed that in healthy postmenopausal female with genotype
      AA birth weight, BMD L2-L4 YA (%) and BMD L2-L4 AM (%) were significantly higher
      (BMD-bone mineral density; L2-L4-- lumbar vertebrae no 2, 4; YA--peak adult bone
      mass; AM--age-matched bone mass). In women with osteopenia BMD L2-L4 YA (%) and
      BMD L2-L4 AM (%) were significantly higher in women with genotype AA, but BMD L2
      L4 was significantly higher in women with genotype TT. In women with osteoporosis
      with genotype AA T-score was significantly higher, but BMD L2-L4 and BMD L2-L4 YA
      (%) were significantly lower in this group. BMD L2-L4 AM (%) was significantly
      higher in women with AA genotype. CONCLUSION: In women with osteoporosis and
      osteopenia homozygous AA genotype may predispose to lower BMD in the lumbar
      spine.

PMID- 25980947
TI  - Conscientiousness and (un)healthy eating: the role of impulsive eating and age in
      the consumption of daily main meals.
AB  - The present study aims to explore the relationship between conscientiousness and
      the consumption of healthy versus unhealthy main meals. Impulsive eating was
      tested as a mediator in this relationship, as well as direct effects of age on
      those constructs. A nationwide representative sample of 1,006 Norwegian adults
      (18-70 years) within a prospective design was used to test a theoretical model.
      The structural equation model (SEM), in combination with bootstrapping procedures
      in AMOS, was the principal analytical method. Conscientiousness was negatively
      associated with unhealthy and impulsive eating. Impulsive eating was a partial
      mediator between conscientiousness and unhealthy eating and a full mediator
      between conscientiousness and healthy eating. Age was positively correlated with
      conscientiousness and this relationship had an inverted U-shape form. Finally,
      age was negatively associated with unhealthy and impulsive eating, and positively
      associated with healthy eating. This study confirmed the relevance of
      conscientiousness for healthy, unhealthy, and impulsive eating. 

PMID- 25980948
TI  - Coronary calcium scores are systematically underestimated at a large chest size:
      A multivendor phantom study.
AB  - OBJECTIVE: To evaluate the effect of chest size on coronary calcium score (CCS)
      as assessed with new-generation CT systems from 4 major vendors. METHODS: An
      anthropomorphic, small-sized (300 * 200 mm) chest phantom containing 100 small
      calcifications (diameters, 0.5-2.0 mm) was evaluated with and without an
      extension ring on state-of-the-art CT systems from 4 vendors. The extension ring
      was used to mimic a patient with a large chest size (400 * 300 mm). Image
      acquisition was repeated 5 times with small translations and/or rotations.
      Routine clinical acquisition and reconstruction protocols for small and large
      patients were used. CCS was quantified as Agatston and mass scores with vendor
      software. RESULTS: The small-sized phantom resulted in median (interquartiles)
      Agatston scores of 10 (9-35), 136 (123-146), 34 (30-37), and 87 (85-89) for
      Philips, GE, Siemens, and Toshiba, respectively. Mass scores were 4 mg (3-9 mg),
      23 mg (21-27 mg), 8 mg (8-9 mg), and 20 mg (20-20 mg), respectively. Adding the
      extension ring resulted in reduced Agatston scores for all vendors (17%-48%) and
      mass scores for 2 vendors (11%-49%). Median Agatston scores decreased to 9 (5
      10), 79 (60-80), 27 (24-32), and 45 (29-53) units, and median mass scores
      remained similar for Philips at 4 mg (4-6 mg) and Siemens at 8 mg (7-8 mg) and
      decreased for the other vendors to 13 mg (11-14 mg) and 10 mg (8-13 mg),
      respectively. CONCLUSION: This multivendor phantom study showed that CCS can be
      underestimated up to 50% (49%-66%) for Agatston scores and 49% (36%-59%) for mass
      scores at a larger chest size, which may be relevant for women and large
      patients. However, CCS underestimation by chest size differs considerably by
      vendor.

PMID- 25980950
TI  - Hamilton's rule: Game theory meets coalescent theory.

PMID- 25980949
TI  - Rapid volumetric T1 mapping of the abdomen using three-dimensional through-time
      spiral GRAPPA.
AB  - PURPOSE: To develop an ultrafast T1 mapping method for high-resolution,
      volumetric T1 measurements in the abdomen. METHODS: The Look-Locker method was
      combined with a stack-of-spirals acquisition accelerated using three-dimensional
      (3D) through-time spiral GRAPPA reconstruction for fast data acquisition. A
      segmented k-space acquisition scheme was proposed and the time delay between
      segments for the recovery of longitudinal magnetization was optimized using Bloch
      equation simulations. The accuracy of this method was validated in a phantom
      experiment and in vivo T1 measurements were performed with 35 asymptomatic
      subjects on both 1.5 Tesla (T) and 3T MRI systems. RESULTS: Phantom experiments
      yielded close agreement between the proposed method and gold standard
      measurements for a large range of T1 values (200 to 1600 ms). The in vivo results
      further demonstrate that high-resolution T1 maps (2 * 2 * 4 mm(3)) for 32 slices
      can be achieved in a single clinically feasible breath-hold of approximately 20
      s. The T1 values for multiple organs and tissues in the abdomen are in agreement
      with the published literature. CONCLUSION: A high-resolution 3D abdominal T1
      mapping technique was developed, which allows fast and accurate T1 mapping of
      multiple abdominal organs and tissues in a single breath-hold.

PMID- 25980951
TI  - Small molecule inhibitor of apoptosis proteins antagonists: a patent review.
AB  - INTRODUCTION: The family of inhibitor of apoptosis proteins (IAPs) plays a key
      role in the suppression of proapoptotic signaling; hence, a small molecule that
      disrupts the binding of IAPs with their functional partner should restore
      apoptotic response to proapoptotic stimuli in cells. The continued publication of
      new patent applications of IAP antagonists over the past 4 years is a testament
      to the continued interest surrounding the IAP family of proteins. AREAS COVERED:
      This review summarizes the IAP antagonist patent literature from 2010 to 2014.
      Monovalent and bivalent Smac mimetics will be covered as well as two new
      developments in the field: IAP antagonists coupled to or merged with other
      targeted agents and new BIR2 selective IAP antagonists. EXPERT OPINION: In
      addition to the well-explored scaffolds for monovalent and bivalent Smac
      mimetics, some companies have taken more drastic approaches to explore new
      chemical space - for example, fragment-based approaches and macrocyclic
      inhibitors. Furthermore, other companies have designed compounds with alternative
      biological profiles - tethering to known kinase binding structures, trying to
      target to the mitochondria or introducing selective binding to the BIR2 domain.
      An overview of the status for the four small molecule IAP antagonists being
      evaluated in active human clinical trials is also provided.

PMID- 25980952
TI  - The Authors Reply: "Association of face-to-face handoffs and outcomes of
      hospitalized internal medicine patients".

PMID- 25980953
TI  - Orientation contrast of secondary electron images from electropolished metals.
AB  - Orientation contrast obtained by an in-lens secondary electron detector in a
      scanning electron microscope from electropolished/etched metals is reported. The
      imaging conditions for obtaining such orientation contrast are defined. The
      mechanism responsible for the formation of the orientation contrast is explained,
      and an application example of this new imaging method is given. 

PMID- 25980954
TI  - Element-specific Kikuchi patterns of Rutile.
AB  - The kinetic energy of keV electrons backscattered from a rutile (TiO2) surface
      depends measurably on the mass of the scattering atom. This makes it possible to
      determine separately the angular distribution of electrons backscattered
      elastically from either Ti or O. Diffraction effects of these backscattered
      electrons inside the rutile crystal lead to the formation of Kikuchi patterns.
      The element-resolved Kikuchi patterns of Ti and O differ characteristically, but
      each can be described fairly well in terms of the dynamical theory of
      diffraction. Qualitatively, much of the differences can be understood by
      considering the relative arrangement of the Ti and O atoms with respect to planes
      defined by the crystal lattice. 

PMID- 25980955
TI  - Three-dimensional morphometric analysis of microglial changes in a mouse model of
      virus encephalitis: age and environmental influences.
AB  - Many RNA virus CNS infections cause neurological disease. Because Piry virus has
      a limited human pathogenicity and exercise reduces activation of microglia in
      aged mice, possible influences of environment and aging on microglial morphology
      and behavior in mice sublethal encephalitis were investigated. Female albino
      Swiss mice were raised either in standard (S) or in enriched (EE) cages from age
      2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral
      tests, mice nostrils were instilled with Piry-virus-infected or with normal brain
      homogenates. Brain sections were immunolabeled for virus antigens or microglia at
      8 days post-infection (dpi), when behavioral changes became apparent, and at 20
      and 40 dpi, after additional behavioral testing. Young infected mice from
      standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in
      burrowing activity and olfactory discrimination, whereas aged infected mice from
      both environments (EAPy, SAPy) showed permanent reduction in both tasks. The
      beneficial effects of an enriched environment were smaller in aged than in young
      mice. Six-hundred and forty microglial cells, 80 from each group were
      reconstructed. An unbiased, stereological sampling approach and multivariate
      statistical analysis were used to search for microglial morphological families.
      This procedure allowed distinguishing between microglial morphology of infected
      and control subjects. More severe virus-associated microglial changes were
      observed in young than in aged mice, and EYPy seem to recover microglial
      homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis
      outcomes were more severe in aged mice, it is suggested that the reduced
      inflammatory response in those individuals may aggravate encephalitis outcomes.

PMID- 25980956
TI  - Relevance drives attention: Attentional bias for gain- and loss-related stimuli
      is driven by delayed disengagement.
AB  - Attentional bias to gain- and loss-related stimuli was investigated in a dot
      probe task. We used coloured stimuli that had acquired their valence during the
      experiment by signalling the chance to either win or lose points in a game task.
      Replicating previous findings with the additional singleton paradigm, we found
      attentional bias effects for both gain- and loss-related colours. The effects
      were due to delayed disengagement from valent stimuli, especially if they were
      positive, and could not be explained by nonattentional processes like behavioural
      freezing. Our findings suggest that stimuli signalling opportunities and dangers
      hold attention, supporting a general motivational relevance principle of the
      orienting of attention. 

PMID- 25980957
TI  - First-Principles Study on the Thermal Stability of LiNiO2 Materials Coated by
      Amorphous Al2O3 with Atomic Layer Thickness.
AB  - Using first-principles calculations, we study how to enhance thermal stability of
      high Ni compositional cathodes in Li-ion battery application. Using the archetype
      material LiNiO2 (LNO), we identify that ultrathin coating of Al2O3 (0001) on
      LNO(012) surface, which is the Li de-/intercalation channel, substantially
      improves the instability problem. Density functional theory calculations indicate
      that the Al2O3 deposits show phase transition from the corundum-type crystalline
      (c-Al2O3) to amorphous (a-Al2O3) structures as the number of coating layers
      reaches three. Ab initio molecular dynamic simulations on the LNO(012) surface
      coated by a-Al2O3 (about 0.88 nm) with three atomic layers oxygen gas evolution
      is strongly suppressed at T=400 K. We find that the underlying mechanism is the
      strong contacting force at the interface between LNO(012) and Al2O3 deposits,
      which, in turn, originated from highly ionic chemical bonding of Al and O at the
      interface. Furthermore, we identify that thermodynamic stability of the a-Al2O3
      is even more enhanced with Li in the layer, implying that the protection for the
      LNO(012) surface by the coating layer is meaningful over the charging process.
      Our approach contributes to the design of innovative cathode materials with not
      only high-energy capacity but also long-term thermal and electrochemical
      stability applicable for a variety of electrochemical energy devices including Li
      ion batteries.

PMID- 25980958
TI  - Identification and genetic characterization of Toxoplasma gondii in free-ranging
      bristle-spined porcupine (Chaetomys subspinosus), a threatened arboreal mammal
      from the Brazilian Atlantic Forest.
AB  - BACKGROUND: Strains of Toxoplasma gondii in Brazil have high genetic diversity
      compared to North America and Europe. The bristle-spined porcupine, Chaetomys
      subspinosus, is often subject to hunting for human food, but it is not known
      whether it can be a reservoir of this parasite. The aim of this study was to
      verify the occurrence of T. gondii in C. subspinosus from southern Bahia, Brazil,
      and genetically characterize and compare the strains found with those isolated in
      previous studies of the same region to quantify their genetic diversity by
      multilocus PCR-RFLP and PCR sequencing. FINDINGS: Twelve free-ranging C.
      subspinosus captured in forest fragments of the Una Biological Reserve and
      adjacent areas were evaluated. Three isolates of T. gondii (TgCsBr01-03) were
      detected. Two different genotypes were identified by applying multilocus PCR-RFLP
      with six molecular markers (SAG1, SAG2, SAG3, c22-8, PK1, and Apico). The
      isolates TgCsBr02 and TgCsBr03 were indistinguishable by this technique. However,
      the three isolates differed from all the reference strains and from the samples
      from the same region. Nevertheless, when the six genetic markers were used in
      multilocus PCR sequencing, all three isolates of T. gondii were different. The
      phylogenetic analysis revealed a greater genetic distance for TgCsBr01, which was
      closer to isolates from pigs from the same region, while TgCsBr02-03 was
      classified in the same lineage and was closer to isolates from sheep from this
      region. CONCLUSIONS: All the isolates differed from the clonal genotypes of types
      I, II, and III using both genotyping techniques.

PMID- 25980959
TI  - Hematological findings in children with brucellosis.
AB  - BACKGROUND: Brucellosis produces a variety of non-specific hematological
      abnormalities. The aim of the present study was to evaluate the hematological
      findings in childhood brucellosis. METHODS: Medical records of children with
      brucellosis admitted to a tertiary hospital in a 1 year period, were analyzed
      retrospectively. RESULTS: Sixty-nine patients (mean age, 14.5 +/- 3.3 years) were
      diagnosed with brucellosis. The most common hematological finding was
      thrombocytopenia (n = 11, 15.9%). Thrombocytosis was detected in five patients
      (7.3%), leukopenia in four (5.8%), anemia in three (4.3%), and bicytopenia in
      three (4.3%). None of the patients had pancytopenia. Blood culture was positive
      for Brucella spp. in 41 patients (59.4%). Among those patients with positive
      blood culture, six (14.6%) had serum agglutination test titer <=1/80. Platelet
      (PLT) count was significantly lower in the bacteremia-positive group. The OR
      (95%CI) of bacteremia for PLT cut-off 200,000/mm(3) was 0.148 (95%CI: 0.031
      0.718) and relative risk was 1.718 (95%CI: 1.244-2.372; P = 0.010). CONCLUSIONS:
      Brucellosis should be kept in mind in the differential diagnosis of isolated
      thrombocytopenia in pediatric patients from endemic areas.

PMID- 25980961
TI  - Constraints on Compliance and the Impact of Health Information in Rural Pakistan.
AB  - The provision of information, which is a common public health strategy, may be
      ineffective if recommendations are not privately optimal for message recipients.
      This paper evaluates the response to a hygiene information campaign in rural
      Pakistan. In a theoretical model, baseline hygiene and health proxy for
      preferences, prices, and wealth, which jointly moderate the impact of
      information. We show that people with good baseline hygiene and health respond
      differentially to the hygiene message. This result, which does not appear to
      arise through differential learning, suggests that practical constraints limit
      the adoption of hygiene recommendations. Information provision may exacerbate
      health inequality under these conditions.

PMID- 25980960
TI  - Rise to modern levels of ocean oxygenation coincided with the Cambrian radiation
      of animals.
AB  - The early diversification of animals (~ 630 Ma), and their development into both
      motile and macroscopic forms (~ 575-565 Ma), has been linked to stepwise
      increases in the oxygenation of Earth's surface environment. However,
      establishing such a linkage between oxygen and evolution for the later Cambrian
      'explosion' (540-520 Ma) of new, energy-sapping body plans and behaviours has
      proved more elusive. Here we present new molybdenum isotope data, which
      demonstrate that the areal extent of oxygenated bottom waters increased in step
      with the early Cambrian bioradiation of animals and eukaryotic phytoplankton.
      Modern-like oxygen levels characterized the ocean at ~ 521 Ma for the first time
      in Earth history. This marks the first establishment of a key environmental
      factor in modern-like ecosystems, where animals benefit from, and also contribute
      to, the 'homeostasis' of marine redox conditions.

PMID- 25980962
TI  - Quantification of length-bias in screening trials with covariate-dependent test
      sensitivity.
AB  - Length-biased sampling exists in screening programs where longer duration disease
      is detected during the preclinical stage because a longer sojourn time
      (preclinical duration) has a higher probability of being screen detected. By
      modeling the course of disease, we quantify the effect of length-biased sampling
      on clinical duration when cases are subject to periodic screening with variable
      test sensitivity. We use the highly flexible bivariate lognormal density to
      jointly model preclinical and clinical durations, and we model screening test
      sensitivity as a function of the sojourn time and number of previous false
      negative screens. We show that the mean clinical duration among screen-detected
      cases can be up to 40% higher, with shrinking standard deviation, than those
      among nonscreen-detected cases, due to biased sampling alone, irrespective of any
      possible benefit (increased survival time arising from earlier detection or
      reduction in mortality). These findings will aid in the design and interpretation
      of screening trials. 

PMID- 25980963
TI  - Authors response to "Deficits of attention and cognition in narcoleptic patients-
      is it hypocretin dependent?".

PMID- 25980964
TI  - Comparison of the usefulness of endoscopic papillary large-balloon dilation with
      endoscopic sphincterotomy for large and multiple common bile duct stones.
AB  - BACKGROUND: Endoscopic sphincterotomy (EST) is currently recognized as the
      primary endoscopic treatment for common bile duct stones. However, it is
      difficult to remove multiple (>= 3) or large (>= 15 mm) common bile duct stones
      with EST alone. Recently, EST plus endoscopic papillary large-balloon dilation
      (EPLBD) was reported to be an effective treatment for such bile duct stones. We
      compared the results of EST and EST + EPLBD for multiple (>= 3) or large (>= 15
      mm) stones that were difficult to treat using EST alone. We also compared the
      complication rates between the techniques. METHODS: Seventy patients with large
      (largest diameter, >= 15 mm) or >= 3 common bile duct stones treated in our
      department between April 2010 and March 2013 underwent EST + EPLBD (n = 34) or
      EST alone (n = 36). We compared final successful stone removal rates, rates of
      successful stone removal in the first session, procedure times, status of
      concurrent mechanical lithotripsy (ML), and complications between the EST + EPLBD
      and EST groups. RESULTS: The rates of final successful stone removal were similar
      between the two groups (EST + EPLBD: 100 % vs. EST: 89 %; p = 0.115). The rate of
      successful stone removal in the first session was significantly higher in the EST
      + EPLBD group (EST + EPLBD: 88 % vs. EST: 56 %; p = 0.03). Moreover, the
      procedure time was significantly shorter (EST + EPLBD: 42 min vs. EST: 67 min; p
      = 0.011) and the rate of ML use was significantly lower in the EST + EPLBD group
      (EST + EPLBD: 50 % vs. EST: 94 %; p < 0.001). Complications like pancreatitis and
      bleeding occurred in three patients in the EST + EPLBD group and in 10 patients
      in the EST group, but the differences were not statistically significant (EST +
      EPLBD: 9 % vs. EST: 25 %; p = 0.112). CONCLUSIONS: Our results suggest that EST +
      EPLBD is an effective therapy for patients with difficult-to-treat multiple or
      large common bile duct stones, because it requires fewer sessions and shorter
      operative times than EST alone.

PMID- 25980965
TI  - Acute and chronic toxicity of tetrabromobisphenol A to three aquatic species
      under different pH conditions.
AB  - Tetrabromobisphenol A (TBBPA) is a well-known brominated flame retardant. It has
      been detected in the environment and shows high acute toxicity to different
      organisms at high concentrations. In this work, the effects of pH and dimethyl
      sulfoxide (DMSO) on the acute toxicity of TBBPA to Daphnia magna and Limnodrilus
      hoffmeisteri were tested, and the oxidative stress induced by TBBPA in livers of
      Carassius auratus was assessed using four biomarkers. The integrated biomarker
      response (IBR) was applied to assess the overall antioxidant status in fish
      livers. Moreover, fish tissues (gills and livers) were also studied
      histologically. The results showed that low pH and DMSO enhanced the toxicity of
      TBBPA. Furthermore, changes in the activity of antioxidant enzymes and
      glutathione level suggested that TBBPA generates oxidative stress in fish livers.
      The IBR index revealed that fish exposed to 3mg/L TBBPA experienced more serious
      oxidative stress than exposed to acidic or alkaline conditions. The
      histopathological analysis revealed lesions caused by TBBPA. This study provides
      valuable toxicological information of TBBPA and will facilitate a deeper
      understanding on its potential toxicity in realistic aquatic environments. 

PMID- 25980966
TI  - Linguistic Validation of the M. D. Anderson Symptom Inventory in Persian-Speaking
      Iranian Cancer Patients.
AB  - CONTEXT: Various symptoms frequently affect cancer patients' quality of life.
      Appropriate assessment of these symptoms provides valuable data for cancer
      management. OBJECTIVES: This study aimed to validate the Persian version of the
      M. D. Anderson Symptom Inventory (MDASI-P). METHODS: This cross-sectional study
      was conducted at four cancer treatment centers in two cities in Iran. Breast
      cancer and colorectal cancer patients aged 18 years and older were consecutively
      included in the study. The standard forward-backward translation method was
      applied. Patients completed the MDASI-P along with the previously validated
      Persian version of the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Construct validity (factor
      analysis), criterion validity (against the EORTC QLQ-C30), and reliability
      (Cronbach's alpha) were analyzed. RESULTS: A total of 146 breast cancer and 94
      colorectal cancer patients were studied. Factor analysis for the symptom severity
      items resulted in a three-factor solution, further reduced to a two-factor
      solution: general symptoms and gastrointestinal symptoms. Correlation of the
      MDASI-P symptom severity items with corresponding EORTC QLQ-C30 symptom items (r
      = 0.48-0.75) and MDASI-P interference items with corresponding EORTC QLQ-C30
      functioning domains (r = -0.46 to -0.23) supported the criterion validity.
      Cronbach's alpha was 0.90, 0.88, and 0.77 for the total questionnaire, symptom
      severity items, and the interference subscale, respectively. CONCLUSION: The
      MDASI-P is a feasible, valid, and reliable instrument for evaluation of symptoms
      in Persian-speaking cancer patients and can be used to improve symptom management
      in these patients.

PMID- 25980967
TI  - Optimal fractionation in radiotherapy with multiple normal tissues.
AB  - The goal in radiotherapy is to maximize the biological effect (BE) of radiation
      on the tumour while limiting its toxic effects on healthy anatomies. Treatment is
      administered over several sessions to give the normal tissue time to recover as
      it has better damage-repair capabilities than tumour cells. This is termed
      fractionation. A key problem in radiotherapy involves finding an optimal number
      of treatment sessions (fractions) and the corresponding dosing schedule. A major
      limitation of existing mathematically rigorous work on this problem is that it
      includes only a single normal tissue. Since essentially no anatomical region of
      interest includes only one normal tissue, these models may incorrectly identify
      the optimal number of fractions and the corresponding dosing schedule. We present
      a formulation of the optimal fractionation problem that includes multiple normal
      tissues. Our model can tackle any combination of maximum dose, mean dose and dose
      volume type constraints for serial and parallel normal tissues as this is
      characteristic of most treatment protocols. We also allow for a spatially
      heterogeneous dose distribution within each normal tissue. Furthermore, we do not
      a priori assume that the doses are invariant across fractions. Finally, our model
      uses a spatially optimized treatment plan as input and hence can be seamlessly
      combined with any treatment planning system. Our formulation is a mixed-integer,
      non-convex, quadratically constrained quadratic programming problem. In order to
      simplify this computationally challenging problem without loss of optimality, we
      establish sufficient conditions under which equal-dosage or single-dosage
      fractionation is optimal. Based on the prevalent estimates of tumour and normal
      tissue model parameters, these conditions are expected to hold in many types of
      commonly studied tumours, such as those similar to head-and-neck and prostate
      cancers. This motivates a simple reformulation of our problem that leads to a
      closed-form formula for the dose per fraction. We then establish that the tumour
      BE is quasiconcave in the number of fractions; this ultimately helps in
      identifying the optimal number of fractions. We perform extensive numerical
      experiments using 10 head-and-neck and prostate test cases to uncover several
      clinically relevant insights.

PMID- 25980968
TI  - Processing Control Information in a Nominal Control Construction: An Eye-Tracking
      Study.
AB  - In an eye-tracking experiment, we examined the processing of the nominal control
      construction. Participants' eye-movements were monitored while they read
      sentences that included either giver control nominals (e.g. promise in Luke's
      promise to Sophia to photograph himself) or recipient control nominals (e.g. plea
      in Luke's plea to Sophia to photograph herself). In order to examine both the
      initial access of control information, and its later use in on-line processing,
      we combined a manipulation of nominal control with a gender match/mismatch
      paradigm. Results showed that there was evidence of processing difficulty for
      giver control sentences (relative to recipient control sentences) at the point
      where the control dependency was initially created, suggesting that control
      information was accessed during the early parsing stages. This effect is
      attributed to a recency preference in the formation of control dependencies; the
      parser prefers to assign a recent antecedent to PRO. In addition, readers slowed
      down after reading a reflexive pronoun that mismatched with the gender of the
      antecedent indicated by the control nominal (e.g. Luke's promise to Sophia to
      photograph herself). The mismatch cost suggests that control information of the
      nominal control construction was used to constrain dependency formation involving
      a controller, PRO and a reflexive, confirming the use of control information in
      on-line interpretation. 

PMID- 25980969
TI  - Universal Restrictions on Syllable Structure: Evidence From Mandarin Chinese.
AB  - Across languages, certain onset clusters are systematically preferred (e.g.,
      [Formula: see text], "[Formula: see text]" indicates preference), and speakers
      extend these preferences even to onsets that are unattested in their language.
      All such demonstrations, however, come from cluster-rich languages, so the
      observed preferences could reflect not universal linguistic restrictions but
      lexical analogy. To address this possibility, here, we turn to Mandarin Chinese-a
      cluster-poor language. We reasoned that, if people are sensitive to the onset
      hierarchy, then they should repair ill-formed onsets as better-formed ones
      [Formula: see text]-the worse formed the onset, the more likely its repair,
      hence, its misidentification. Results were consistent with this hypothesis, and
      they obtained irrespective of participants' experience with their second language
      (English). Nonetheless, the effect of syllable structure was strongly modulated
      by phonetic cues and task demands. These findings suggest that speakers might
      share broad phonological restrictions, but phonetic factors play a major role in
      their detection. 

PMID- 25980970
TI  - ERP Study of Affirmative and Negative Sentences' Impact on Self-Positivity Bias.
AB  - To explore how the sentence contexts affect self-positivity bias, we presented
      the participants with negation and affirmation sentences. Each sentence was ended
      with an adjective word describing human being's personality. The participants
      were asked to judge whether the sentences correctly described their own
      personalities. In affirmation sentences, the behavioral data showed that self
      positivity bias occurred when participants considered the sentences to be in
      accordance with their personality; the ERP data showed that P200 amplitude was
      consistent with this behavioral result. In negation sentences, behavioral data
      showed self-positivity bias, regardless of whether the sentences were in
      accordance with participants' personality or not. However, the self-positivity
      bias was not observed in the ERP results from negation sentence. In summary,
      sentence type modulated the effect of self-positivity bias. The reason could be
      that processing affirmation and negation sentences requires different amount of
      cognitive resources. 

PMID- 25980972
TI  - Impact of climate change and water use policies on hydropower potential in the
      south-eastern Alpine region.
AB  - Climate change is expected to cause alterations of streamflow regimes in the
      Alpine region, with possible relevant consequences for several socio-economic
      sectors including hydropower production. The impact of climate change on water
      resources and hydropower production is evaluated with reference to the Noce
      catchment, which is located in the Southeastern Alps, Italy. Projected changes of
      precipitation and temperature, derived from an ensemble of 4 climate model (CM)
      runs for the period 2040-2070 under the SRES A1B emission scenario, have been
      downscaled and bias corrected before using them as climatic forcing in a
      hydrological model. Projections indicate an increase of the mean temperature of
      the catchment in the range 2-4K, depending on the climate model used. Projections
      of precipitation indicate an increase of annual precipitation in the range
      between 2% and 6% with larger changes in winter and autumn. Hydrological
      simulations show an increase of water yield during the period 2040-2070 with
      respect to 1970-2000. Furthermore, a transition from glacio-nival to nival regime
      is projected for the catchment. Hydrological regime is expected to change as a
      consequence of less winter precipitation falling as snow and anticipated melting
      in spring, with the runoff peak decreasing in intensity and anticipating from
      July to June. Changes in water availability reflect in the Technical Hydropower
      Potential (THP) of the catchment, with larger changes projected for the
      hydropower plants located at the highest altitudes. Finally, the impacts on THP
      of water use policies such as the introduction of prescriptions for minimum
      ecological flow (MEF) have been analyzed. Simulations indicate that in the lower
      part of the catchment reduction of the hydropower production due to MEF releases
      from the storage reservoirs counterbalances the benefits associated to the
      projected increases of inflows as foreseen by simulations driven only by climate
      change. 

PMID- 25980971
TI  - The Role of Secondary-Stressed and Unstressed-Unreduced Syllables in Word
      Recognition: Acoustic and Perceptual Studies with Russian Learners of English.
AB  - The importance of secondary-stressed (SS) and unstressed-unreduced (UU) syllable
      accuracy for spoken word recognition in English is as yet unclear. An acoustic
      study first investigated Russian learners' of English production of SS and UU
      syllables. Significant vowel quality and duration reductions in Russian-spoken SS
      and UU vowels were found, likely due to a transfer of native phonological
      features. Next, a cross-modal phonological priming technique combined with a
      lexical decision task assessed the effect of inaccurate SS and UU syllable
      productions on native American English listeners' speech processing. Inaccurate
      UU vowels led to significant inhibition of lexical access, while reduced SS
      vowels revealed less interference. The results have implications for
      understanding the role of SS and UU syllables for word recognition and English
      pronunciation instruction. 

PMID- 25980973
TI  - Transgenic poplar expressing Arabidopsis YUCCA6 exhibits auxin-overproduction
      phenotypes and increased tolerance to abiotic stress.
AB  - YUCCA6, a member of the YUCCA family of flavin monooxygenase-like proteins, is
      involved in the tryptophan-dependent IAA biosynthesis pathway and responses to
      environmental cues in Arabidopsis. However, little is known about the role of the
      YUCCA pathway in auxin biosynthesis in poplar. Here, we generated transgenic
      poplar (Populus alba * P. glandulosa) expressing the Arabidopsis YUCCA6 gene
      under the control of the oxidative stress-inducible SWPA2 promoter (referred to
      as SY plants). Three SY lines (SY7, SY12 and SY20) were selected based on the
      levels of AtYUCCA6 transcript. SY plants displayed auxin-overproduction
      morphological phenotypes, such as rapid shoot growth and retarded main root
      development with increased root hair formation. In addition, SY plants had higher
      levels of free IAA and early auxin-response gene transcripts. SY plants exhibited
      tolerance to drought stress, which was associated with reduced levels of reactive
      oxygen species. Furthermore, SY plants showed delayed hormone- and dark-induced
      senescence in detached leaves due to higher photosystem II efficiency and less
      membrane permeability. These results suggest that the conserved IAA biosynthesis
      pathway mediated by YUCCA family members exists in poplar. 

PMID- 25980974
TI  - What has mathematics done for biology?

PMID- 25980976
TI  - Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal
      in Iminium Ion Activation.
AB  - Invited for the cover of this issue is the group of Ryan Gilmour at the
      Westfalische Wilhelms-Universitat Munster. The image depicts how the modes of
      stereoinduction differ for- N-methylpyrrole to- N-methylindole. Read the full
      text of the article at 10.1002/chem.201500270. 

PMID- 25980975
TI  - Resting state signatures of domain and demand-specific working memory
      performance.
AB  - Working memory (WM) is one of the key constructs in understanding higher-level
      cognition. We examined whether patterns of activity in the resting state of
      individual subjects are correlated with their off-line working and short-term
      memory capabilities. Participants completed a resting-state fMRI scan and off
      line working and short-term memory (STM) tests with both verbal and visual
      materials. We calculated fractional amplitude of low frequency fluctuations
      (fALFF) from the resting state data, and also computed connectivity between seeds
      placed in frontal and parietal lobes. Correlating fALFF values with behavioral
      measures showed that the fALFF values in a widespread fronto-parietal network
      during rest were positively correlated with a combined memory measure. In
      addition, STM showed a significant correlation with fALFF within the right
      angular gyrus and left middle occipital gyrus, whereas WM was correlated with
      fALFF values within the right IPS and left dorsomedial cerebellar cortex.
      Furthermore, verbal and visuospatial memory capacities were associated with
      dissociable patterns of low-frequency fluctuations. Seed-based connectivity
      showed correlations with the verbal WM measure in the left hemisphere, and with
      the visual WM measure in the right hemisphere. These findings contribute to our
      understanding of how differences in spontaneous low-frequency fluctuations at
      rest are correlated with differences in cognitive performance. 

PMID- 25980977
TI  - Out of the orphanage and into the clinic--therapeutic targeting of GATA3.

PMID- 25980978
TI  - Designed blending for near infrared calibration.
AB  - Spectroscopic methods are increasingly used for monitoring pharmaceutical
      manufacturing unit operations that involve powder handling and processing. With
      that regard, chemometric models are required to interpret the obtained spectra.
      There are many ways to prepare artificial powder blend samples used in a
      chemometric model for predicting the chemical content. Basically, an infinite
      number of possible concentration levels exist in terms of the individual
      components. In our study, design of experiments for ternary mixtures was used to
      establish a suitable number of blend compositions that represents the entire
      mixture region of interest for a three component blend. Various experimental
      designs and their effect on the predictive power of a chemometric model for near
      infrared spectra were investigated. It was determined that a particular choice of
      experimental design could change the predictive power of a model, even with the
      same number of calibration experiments.

PMID- 25980979
TI  - Activation of brain steroidogenesis and neurogenesis during the gonadal
      differentiation in protandrous black porgy, Acanthopagrus schlegelii.
AB  - The early brain development, at the time of gonadal differentiation was
      investigated using a protandrous teleost, black porgy. This natural model of
      monosex juvenile fish avoids the potential complexity of sexual dimorphism. Brain
      neurogenesis was evaluated by histological analyses of the diencephalon, at the
      time of testicular differentiation (in fish between 90 and 150 days after
      hatching). Increases in the number of both Nissl-stained total brain cells, and
      Pcna-immunostained proliferative brain cells were observed in specific area of
      the diencephalon, such as ventromedialis thalami and posterior preoptic area,
      revealing brain cell proliferation. qPCR analyses showed significantly higher
      expression of the radial glial cell marker blbp and neuron marker bdnf. Strong
      immunohistochemical staining of Blbp and extended cellular projections were
      observed. A peak expression of aromatase (cyp19a1b), as well as an increase in
      estradiol (E2 ) content were also detected in the early brain. These data
      demonstrate that during gonadal differentiation, the early brain exhibits
      increased E2 synthesis, cell proliferation, and neurogenesis. To investigate the
      role of E2 in early brain, undifferentiated fish were treated with E2 or
      aromatase inhibitor (AI). E2 treatment upregulated brain cyp19a1b and blbp
      expression, and enhanced brain cell proliferation. Conversely, AI reduced brain
      cell proliferation. Castration experiment did not influence the brain gene
      expression patterns and the brain cell number. Our data clearly support E2
      biosynthesis in the early brain, and that brain E2 induces neurogenesis. These
      peak activity patterns in the early brain occur at the time of gonad
      differentiation but are independent of the gonads.

PMID- 25980980
TI  - Coronary Thrombosis and Type A Aortic Dissection.
AB  - A 74-year-old female had urgent surgery with replacement of the ascending aorta
      for acute type A dissection. Postprocedure, the electrocardiogram showed an ST
      segment elevation myocardial infarction in the antero-lateral leads. Angiography
      revealed a thrombotic occlusion of the left anterior descending artery, treated
      successfully with bivalirudin administration, thrombus aspiration and a balloon
      angioplasty. This case involves the rare coexistence of acute type A aortic
      dissection and myocardial infarction due to coronary plaque thrombosis.

PMID- 25980981
TI  - A PEGylated photocleavable auxiliary mediates the sequential enzymatic
      glycosylation and native chemical ligation of peptides.
AB  - Research aimed at understanding the specific role of glycosylation patterns in
      protein function would greatly benefit from additional approaches allowing direct
      access to homogeneous glycoproteins. Herein the development and application of an
      efficient approach for the synthesis of complex homogenously glycosylated
      peptides based on a multifunctional photocleavable auxiliary is described. The
      presence of a PEG polymer within the auxiliary enables sequential enzymatic
      glycosylation and straightforward isolation in excellent yields. The auxiliary
      modified peptides can be directly used in native chemical ligations with peptide
      thioesters easily obtained by direct hydrazinolysis of the respective
      glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides
      can be smoothly deprotected by UV irradiation. We apply this approach to the
      preparation of variants of the epithelial tumor marker MUC1 carrying one or more
      Tn, T, or sialyl-T antigens. 

PMID- 25980983
TI  - Middle latency response correlates of single and double deviant stimuli in a
      multi-feature paradigm.
AB  - OBJECTIVE: This study aimed to test single and double deviance-related
      modulations of the middle latency response (MLR) and the applicability of the
      optimum-2 multi-feature paradigm. METHODS: The MLR and the MMN to frequency,
      intensity and double-feature deviants of an optimum-2 multi-feature paradigm and
      the MMN to double-feature deviants of an oddball paradigm were recorded in young
      adults. RESULTS: Double deviants elicited significant enhancements of the Nb and
      Pb MLR waves compared with the waves elicited by standard stimuli. These
      enhancements equalled approximately the sum of the numerical amplitude
      differences elicited by the single deviants. In contrast, the MMN to double
      deviants did not show such additivity. MMNs elicited by double deviants of the
      multi-feature and the oddball paradigm showed no significant difference in
      amplitude or latency. CONCLUSIONS: The optimum-2 multi-feature paradigm is
      suitable for recording double deviance-related modulations of the MLR.
      Interspersed intensity and frequency deviants in the standard trace of the
      optimum-2 condition multi-feature paradigm did not weaken the double MMN.
      SIGNIFICANCE: The optimum-2 multi-feature paradigm could be especially beneficial
      for clinical studies on early deviance-related modulations in the MLR, due to its
      optimized utilization of the recording time.

PMID- 25980982
TI  - Curcumin-encapsulated polymeric micelles suppress the development of colon cancer
      in vitro and in vivo.
AB  - To develop injectable formulation and improve the stability of curcumin (Cur),
      Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (epsilon
      caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through
      a single-step solid dispersion method. The obtained Cur micelles had a small
      particle size of 27.6 +/- 0.7 nm with polydisperse index (PDI) of 0.11 +/- 0.05,
      drug loading of 14.07 +/- 0.94%, and encapsulation efficiency of 96.08 +/- 3.23%.
      Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon
      carcinoma cells in vitro. The results of in vitro anticancer studies confirmed
      that apoptosis induction and cellular uptake on CT26 cells had completely
      increased in Cur micelles compared with free Cur. Besides, Cur micelles were more
      effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and
      the mechanisms included the inhibition of tumor proliferation and angiogenesis
      and increased apoptosis of tumor cells. Furthermore, few side effects were found
      in Cur micelles. Overall, our findings suggested that Cur micelles could be a
      stabilized aqueous formulation for intravenous application with improved
      antitumor activity, which may be a potential treatment strategy for colon cancer
      in the future.

PMID- 25980984
TI  - Supported self-management for patients with moderate to severe chronic
      obstructive pulmonary disease (COPD): an evidence synthesis and economic
      analysis.
AB  - BACKGROUND: Self-management (SM) support for patients with chronic obstructive
      pulmonary disease (COPD) is variable in its coverage, content, method and timing
      of delivery. There is insufficient evidence for which SM interventions are the
      most effective and cost-effective. OBJECTIVES: To undertake (1) a systematic
      review of the evidence for the effectiveness of SM interventions commencing
      within 6 weeks of hospital discharge for an exacerbation for COPD (review 1); (2)
      a systematic review of the qualitative evidence about patient satisfaction,
      acceptance and barriers to SM interventions (review 2); (3) a systematic review
      of the cost-effectiveness of SM support interventions within 6 weeks of hospital
      discharge for an exacerbation of COPD (review 3); (4) a cost-effectiveness
      analysis and economic model of post-exacerbation SM support compared with usual
      care (UC) (economic model); and (5) a wider systematic review of the evidence of
      the effectiveness of SM support, including interventions (such as pulmonary
      rehabilitation) in which there are significant components of SM, to identify
      which components are the most important in reducing exacerbations, hospital
      admissions/readmissions and improving quality of life (review 4). METHODS: The
      following electronic databases were searched from inception to May 2012: MEDLINE,
      MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central
      Register of Controlled Trials (CENTRAL), and Science Citation Index [Institute of
      Scientific Information (ISI)]. Subject-specific databases were also searched:
      PEDro physiotherapy evidence database, PsycINFO and the Cochrane Airways Group
      Register of Trials. Ongoing studies were sourced through the metaRegister of
      Current Controlled Trials, International Standard Randomised Controlled Trial
      Number database, World Health Organization International Clinical Trials Registry
      Platform Portal and ClinicalTrials.gov. Specialist abstract and conference
      proceedings were sourced through ISI's Conference Proceedings Citation Index and
      British Library's Electronic Table of Contents (Zetoc). Hand-searching through
      European Respiratory Society, the American Thoracic Society and British Thoracic
      Society conference proceedings from 2010 to 2012 was also undertaken, and
      selected websites were also examined. Title, abstracts and full texts of
      potentially relevant studies were scanned by two independent reviewers. Primary
      studies were included if ~90% of the population had COPD, the majority were of at
      least moderate severity and reported on any intervention that included a SM
      component or package. Accepted study designs and outcomes differed between the
      reviews. Risk of bias for randomised controlled trials (RCTs) was assessed using
      the Cochrane tool. Random-effects meta-analysis was used to combine studies where
      appropriate. A Markov model, taking a 30-year time horizon, compared a SM
      intervention immediately following a hospital admission for an acute exacerbation
      with UC. Incremental costs and quality-adjusted life-years were calculated, with
      sensitivity analyses. RESULTS: From 13,355 abstracts, 10 RCTs were included for
      review 1, one study each for reviews 2 and 3, and 174 RCTs for review 4.
      Available studies were heterogeneous and many were of poor quality. Meta-analysis
      identified no evidence of benefit of post-discharge SM support on admissions
      [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.52 to 1.17], mortality
      (HR 1.07, 95% CI 0.74 to 1.54) and most other health outcomes. A modest
      improvement in health-related quality of life (HRQoL) was identified but this was
      possibly biased due to high loss to follow-up. The economic model was speculative
      due to uncertainty in impact on readmissions. Compared with UC, post-discharge SM
      support (delivered within 6 weeks of discharge) was more costly and resulted in
      better outcomes (L683 cost difference and 0.0831 QALY gain). Studies assessing
      the effect of individual components were few but only exercise significantly
      improved HRQoL (3-month St George's Respiratory Questionnaire 4.87, 95% CI 3.96
      to 5.79). Multicomponent interventions produced an improved HRQoL compared with
      UC (mean difference 6.50, 95% CI 3.62 to 9.39, at 3 months). Results were
      consistent with a potential reduction in admissions. Interventions with more
      enhanced care from health-care professionals improved HRQoL and reduced
      admissions at 1-year follow-up. Interventions that included supervised or
      unsupervised structured exercise resulted in significant and clinically important
      improvements in HRQoL up to 6 months. LIMITATIONS: This review was based on a
      comprehensive search strategy that should have identified most of the relevant
      studies. The main limitations result from the heterogeneity of studies available
      and widespread problems with their design and reporting. CONCLUSIONS: There was
      little evidence of benefit of providing SM support to patients shortly after
      discharge from hospital, although effects observed were consistent with possible
      improvement in HRQoL and reduction in hospital admissions. It was not easy to
      tease out the most effective components of SM support packages, although
      interventions containing exercise seemed the most effective. Future work should
      include qualitative studies to explore barriers and facilitators to SM post
      exacerbation and novel approaches to affect behaviour change, tailored to the
      individual and their circumstances. Any new trials should be properly designed
      and conducted, with special attention to reducing loss to follow-up. Individual
      participant data meta-analysis may help to identify the most effective components
      of SM interventions. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42011001588. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 25980985
TI  - Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double
      Bridge Strategy.
AB  - In patients requiring left ventricular assist device (LVAD) support, it can be
      difficult to ascertain suitability for long-term mechanical support with LVAD and
      eventual transplantation. LVAD implantation in a shocked patient is associated
      with increased morbidity and mortality. Interest is growing in the utilization of
      extracorporeal life support (ECLS) as a bridge-to-bridge support for these
      critically unwell patients. Here, we reviewed our experience with ECLS double
      bridging. We hypothesized that ECLS double bridging would stabilize end-organ
      dysfunction and reduce ventricular assist device (VAD) implant perioperative
      mortality. We conducted a retrospective review of prospectively collected data
      for 58 consecutive patients implanted with a continuous-flow LVAD between January
      2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia.
      Twenty-three patients required ECLS support pre-LVAD while 35 patients underwent
      LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS
      bridge group was reflected by increased postoperative intensive care duration,
      blood loss, blood product use, and postoperative renal failure, but without
      negative impact upon survival when compared with the no ECLS group. ECLS
      stabilization improved end-organ function pre-VAD implant with significant
      improvements in hepatic and renal dysfunction. This series demonstrates that the
      use of ECLS bridge to VAD stabilizes end-organ dysfunction and reduces VAD
      implant perioperative mortality from that traditionally reported in these "crash
      and burn" patients. 

PMID- 25980986
TI  - Graphene-based membranes.
AB  - Graphene is a well-known two-dimensional material that exhibits preeminent
      electrical, mechanical and thermal properties owing to its unique one-atom-thick
      structure. Graphene and its derivatives (e.g., graphene oxide) have become
      emerging nano-building blocks for separation membranes featuring distinct laminar
      structures and tunable physicochemical properties. Extraordinary molecular
      separation properties for purifying water and gases have been demonstrated by
      graphene-based membranes, which have attracted a huge surge of interest during
      the past few years. This tutorial review aims to present the latest
      groundbreaking advances in both the theoretical and experimental chemical science
      and engineering of graphene-based membranes, including their design, fabrication
      and application. Special attention will be given to the progresses in processing
      graphene and its derivatives into separation membranes with three distinct forms:
      a porous graphene layer, assembled graphene laminates and graphene-based
      composites. Moreover, critical views on separation mechanisms within graphene
      based membranes will be provided based on discussing the effect of inter-layer
      nanochannels, defects/pores and functional groups on molecular transport.
      Furthermore, the separation performance of graphene-based membranes applied in
      pressure filtration, pervaporation and gas separation will be summarized. This
      article is expected to provide a compact source of relevant and timely
      information and will be of great interest to all chemists, physicists, materials
      scientists, engineers and students entering or already working in the field of
      graphene-based membranes and functional films. 

PMID- 25980987
TI  - Movement is the glue connecting home ranges and habitat selection.
AB  - Animal space use has been studied by focusing either on geographic (e.g. home
      ranges, species' distribution) or on environmental (e.g. habitat use and
      selection) space. However, all patterns of space use emerge from individual
      movements, which are the primary means by which animals change their environment.
      Individuals increase their use of a given area by adjusting two key movement
      components: the duration of their visit and/or the frequency of revisits. Thus,
      in spatially heterogeneous environments, animals exploit known, high-quality
      resource areas by increasing their residence time (RT) in and/or decreasing their
      time to return (TtoR) to these areas. We expected that spatial variation in these
      two movement properties should lead to observed patterns of space use in both
      geographic and environmental spaces. We derived a set of nine predictions linking
      spatial distribution of movement properties to emerging space-use patterns. We
      predicted that, at a given scale, high variation in RT and TtoR among habitats
      leads to strong habitat selection and that long RT and short TtoR result in a
      small home range size. We tested these predictions using moose (Alces alces) GPS
      tracking data. We first modelled the relationship between landscape
      characteristics and movement properties. Then, we investigated how the spatial
      distribution of predicted movement properties (i.e. spatial autocorrelation,
      mean, and variance of RT and TtoR) influences home range size and hierarchical
      habitat selection. In landscapes with high spatial autocorrelation of RT and
      TtoR, a high variation in both RT and TtoR occurred in home ranges. As expected,
      home range location was highly selective in such landscapes (i.e. second-order
      habitat selection); RT was higher and TtoR lower within the selected home range
      than outside, and moose home ranges were small. Within home ranges, a higher
      variation in both RT and TtoR was associated with higher selectivity among
      habitat types (i.e. third-order habitat selection). Our findings show how
      patterns of geographic and environmental space use correspond to the two sides of
      a coin, linked by movement responses of individuals to environmental
      heterogeneity. By demonstrating the potential to assess the consequences of
      altering RT or TtoR (e.g. through human disturbance or climatic changes) on home
      range size and habitat selection, our work sets the basis for new theoretical and
      methodological advances in movement ecology. 

PMID- 25980988
TI  - In reply: is dexmedetomidine really superior to propofol?

PMID- 25980990
TI  - Design of High-Mobility Diketopyrrolopyrrole-Based pi-Conjugated Copolymers for
      Organic Thin-Film Transistors.
AB  - Since the report of the first diketopyrrolopyrrole (DPP)-based polymer
      semiconductor, such polymers have received considerable attention as a promising
      candidate for high-performance polymer semiconductors in organic thin-film
      transistors (OTFTs). This Progress Report summarizes the advances in the
      molecular design of high-mobility DPP-based polymers reported in the last few
      years, especially focusing on the molecular design of these polymers in respect
      of tuning the backbone and side chains, and discussing the influences of
      structural modification of the backbone and side chains on the properties and
      device performance of corresponding DPP-based polymers. This provides insights
      for the development of new and high-mobility polymer semiconductors. 

PMID- 25980989
TI  - Effect of sevoflurane on human hepatocellular carcinoma HepG2 cells under
      conditions of high glucose and insulin.
AB  - Diabetes mellitus is associated with morbidity and progression of some cancers,
      such as hepatocellular carcinoma. It has been reported that sevoflurane, a
      volatile anesthetic agent commonly used in cancer surgery, can lead to lower
      overall survival rates than those observed when propofol is used to treat cancer
      patients, and sevoflurane increases cancer cell proliferation in in vitro
      studies. It has been also reported that glucose levels in rats anesthetized with
      sevoflurane were higher than those in rats anesthetized with propofol. We
      investigated the effect of sevoflurane, under conditions of high glucose and
      insulin, on cell proliferation in the human hepatocellular carcinoma cell line,
      HepG2. First, we exposed HepG2 cells to sevoflurane at 1 or 2 % concentration for
      6 h in various glucose concentrations and then evaluated cell proliferation using
      the MTT assay. Subsequently, to mimic diabetic conditions observed during
      surgery, HepG2 cells were exposed to sevoflurane at 1 or 2 % concentration in
      high glucose concentrations at various concentrations of insulin for 6 h. One
      percent sevoflurane exposure enhanced cell proliferation under conditions of high
      glucose, treated with 0.05 mg/l insulin. Our study implies that sevoflurane may
      affect cell proliferation in human hepatocellular carcinoma cells in a
      physiological situation mimicking that of diabetes.

PMID- 25980991
TI  - Quantitative immunohistochemical co-localization of TRPV1 and CGRP in varicose
      axons of the murine oesophagus, stomach and colorectum.
AB  - In the gastrointestinal (GI) tract of mammals, endings of spinal afferent neurons
      with cell bodies in dorsal root ganglia (DRG) detect many stimuli, including
      those that give rise to pain. Many of these sensory neurons express calcitonin
      gene-related peptide (CGRP) and TRPV1 in their cell bodies and axons. Indeed,
      CGRP and TRPV1 have been widely used as immunohistochemical markers of
      nociceptive spinal afferent axons. Although CGRP and TRPV1 often coexist in the
      same axons in the GI tract, their degree of coexistence along its length has yet
      to be quantified. In this study, we used double-labeling immunohistochemistry to
      quantify the coexistence of CGRP and TRPV1 in varicose axons of the murine
      oesophagus, stomach and colorectum. The great majority of CGRP-immunoreactive
      (IR) varicosities in myenteric ganglia of the lower esophagus (97+/-1%) and
      stomach (95+/-1%) were also TRPV1-immunoreactive. Similarly, the majority of
      TRPV1-IR varicosities in myenteric ganglia of the lower esophagus (95+/-1%) and
      stomach (91+/-1%) were also CGRP-IR. In the colorectum similar observations were
      made for an intensely immunoreactive population of CGRP-IR axons, of which most
      (91+/-1%) were also TRPV1-IR. Of the TRPV1-IR axons in the colorectum, most (96+/
      1%) contained intense CGRP-IR. Another population of axons in myenteric ganglia
      of the colorectum had low intensity CGRP immunoreactivity; these showed
      negligible co-existence with TRPV1. Our observations reveal that in the myenteric
      plexus of murine oesophagus, stomach and colorectum, CGRP and TRPV1 are largely
      expressed together. 

PMID- 25980992
TI  - Neural tissue regeneration in experimental brain injury model with channeled
      scaffolds of acrylate copolymers.
AB  - The objective of the present study was to evaluate the biocompatibility and cell
      hosting ability of a copolymer scaffold based on ethyl acrylate (EA) and hydroxyl
      ethyl acrylate (HEA) in vivo after an experimental brain injury. Wistar rats were
      subjected to cryogenic traumatic brain injury. We evaluated the tissue response
      to the implanted materials after 8 weeks. The materials were implanted devoid of
      cells; they provoked a minimal scar response by the host tissue and permitted the
      invasion of neurons and glia inside them. We also found new blood vessels
      surrounding and inside the implant. Thus, the copolymer scaffold proves to offer
      a suitable environment producing a cellular network potentially useful in brain
      repair after brain injury. 

PMID- 25980993
TI  - Ketamine-mediated alleviation of electroconvulsive shock-induced memory
      impairment is associated with the regulation of neuroinflammation and soluble
      amyloid-beta peptide in depressive-like rats.
AB  - Electroconvulsive therapy (ECT) is an effective treatment for depression, but can
      result in memory deficits. This study aimed to determine whether ketamine could
      alleviate electroconvulsive shock (ECS, an analog of ECT in animals)-induced
      memory impairment and the potential molecular mechanism. Chronic unpredictable
      mild stress was used to generate animal models of depressive-like symptoms. Sixty
      adult male Sprague-Dawley rats were randomly divided into the following five
      groups: control group (group C); depressive-like model group (group D); ECS group
      (group DE); ketamine+ECS group (group DKE); and ketamine group (group DK). The
      sucrose preference test and Morris water maze were used to assess behavioral
      changes. The expression levels of Iba-1, IL-1beta and TNF-alpha were measured by
      immunohistochemistry and real-time PCR. Enzyme-linked immunosorbent assays were
      used to detect the levels of soluble Abeta. We found that ECS up-regulated the
      expression of Iba-1, promoted the release of IL-1beta and TNF-alpha, increased
      the levels of Abeta1-40 and Abeta1-42 in the hippocampus, and aggravated memory
      impairment of the depressive-like rats. However, ketamine reversed these ECS
      induced molecular changes and effectively attenuated ECS-induced memory
      impairment. This cognitive protective effect of ketamine may be attributed to its
      suppression of ECS-induced neuroinflammation and reduction of the levels of
      soluble Abeta. 

PMID- 25980994
TI  - Autophagy in spinal motor neurons of conditional ADAR2-knockout mice: An
      implication for a role of calcium in increased autophagy flux in ALS.
AB  - In the motor neurons of amyotrophic lateral sclerosis (ALS) patients, an RNA
      editing enzyme called adenosine deaminase acting on RNA 2 (ADAR2) is down
      regulated and consequently GluA2 mRNAs unedited at the Q/R site is expressed in
      contrast to normal motor neurons that express only GluA2 edited at this site.
      Motor neurons of the mice lacking ADAR2 undergo Ca(2+)-permeable AMPA receptor
      mediated slow death. We investigated the spinal cords of conditional ADAR2
      knockout mice modeling ALS for the involvement of autophagy. In the motor neurons
      of the early- and late-symptomatic-stage mice, LC3-immunopositivity or
      immunoreactivity for both LC3- and p62 was observed, whereas the presymptomatic
      stage mice showed no LC3- or p62-immunoreactivity. Western blot analyses showed
      increased expression of autophagy associated proteins in the anterior horn of the
      early symptomatic-stage mice. Electron-microscopically, autophagy was observed in
      the motor neurons most frequently in the early-symptomatic-stage mice which
      showed the severest motor neuron degeneration. Increased autophagy flux was not
      recognized in the wild-type mice or AR2res (ADAR2(flox/flox)/VAChT-Cre. Fast/GluR
      B(R)(/)(R)) mice having motor neurons genetically engineered to express normally
      edited GluA2 in the absence of ADAR2, which show normal Ca(2+)-permeability of
      the AMPA receptors in motor neurons. Significantly increased autophagy flux in
      the degenerating motor neurons of ADAR2-knockout mice likely resulted from Ca(2+)
      overload. 

PMID- 25980995
TI  - Effect of adenosine system in the action of oseltamivir on behavior in mice.
AB  - Abnormal behaviors and death associated with the use of oseltamivir
      (Tamiflu((r))) have emerged as a major issue in influenza patients. We have
      previously reported that the mechanisms underlying the effects of caffeine, a non
      selective adenosine A1/A2 receptor antagonist, combined with oseltamivir.
      Oseltamivir is rapidly hydrolyzed to its active form (oseltamivir carboxylate,
      OCB). In this study, we investigated the effects of an adenosine system and OCB
      on the action of oseltamivir on mice behavior. Oseltamivir for 1 day (150 mg/kg,
      intraperitoneally (i.p.)) alone did not affect ambulation at 2 h post-injection.
      However, caffeine (10 mg/kg, i.p.) in combination with oseltamivir for 1 day
      increased ambulation. Moreover, caffeine (30 mg/kg, i.p.) in combination with
      oseltamivir for 3 days increased ambulation, but caffeine (10 mg/kg, i.p.) in
      combination with oseltamivir for 3 days did not increase. These enhancements were
      inhibited by an adenosine A2 receptor agonist, CGS21680 (0.2 mg/kg,
      subcutaneously (s.c.)). Furthermore, an adenosine A2 receptor antagonist,
      SCH58261 (1 and 3 mg/kg, i.p.) in combination with oseltamivir for 1 day
      increased ambulation. Moreover, SCH58261 (3 mg/kg, i.p.) in combination with
      oseltamivir for 3 days increased ambulation, but SCH58261 (1 mg/kg, i.p.) in
      combination with oseltamivir for 3 days did not. Conversely, in phenobarbital
      (PB)-treated mice, caffeine (3 mg/kg, i.p.) in combination with oseltamivir for 1
      day increased ambulation. Moreover, OCB for 1 day (0.3 MUg/mouse
      intracerebroventricular (i.c.v.)) alone increased ambulation. These findings
      suggest that the actions of oseltamivir may involve the adenosine systems and its
      metabolism. Our findings suggest an interaction between the central blockade of
      adenosine A2 receptors by caffeine and OCB-induced behavioral changes.

PMID- 25980996
TI  - Neuroprotective effect of lycopene against MPTP induced experimental Parkinson's
      disease in mice.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      that mainly affects the movement of the aged populations. Lycopene is a
      carotenoid with unique pharmacological properties and its efficacy on
      experimental Hunginton's disease and brain ischemia has shown intense
      neuroprotective effects. The present study was aimed to explore the
      neuroprotective effect of lycopene against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) induced PD mice. Administration of lycopene (5, 10 and
      20 mg/kg/day orally) protected MPTP induced depletion of striatal dopamine (DA)
      and its metabolites in a dose dependent manner. It also attenuated MPTP-induced
      oxidative stress and motor abnormalities seen in PD mice. Our western blot
      studies showed that treatment with lycopene reversed MPTP induced apoptosis may
      be due to its antioxidant and antiapoptotic properties. As to conclude, lycopene
      reverses neurochemical deficts, oxidative stress, apoptosis and physiological
      abnormalities in PD mice and offer promise strategy in the treatment of this
      neurodegenerative disease.

PMID- 25980997
TI  - Chewing suppresses the stress-induced increase in the number of pERK
      immunoreactive cells in the periaqueductal grey.
AB  - We investigated the effects of chewing under immobilization stress on the
      periaqueductal gray (PAG) matter using phosphorylated extracellular signal
      regulated kinase (pERK) as a marker of responding cells. Immobilization stress
      increased pERK-immunoreactive cells in the PAG. Among four subdivisions of the
      PAG, the increase of immunoreactive cells was remarkable in the dorsolateral and
      ventrolateral subdivisions. However, increase of pERK-immunoreactive cells by the
      immobilization stress was not so evident in the dorsomedial and lateral
      subdivisions. The chewing under immobilization stress prevented the stress
      induced increase of pERK-immunoreactive cells in the dorsolateral and
      ventrolateral subdivisions with statistical significances (p<0.05). Again,
      chewing effects on pERK-immunoreactive cells were not visible in the dorsomedial
      and lateral subdivisions. These results suggest that the chewing alleviates the
      PAG (dorsolateral and ventrolateral subdivisions) responses to stress. 

PMID- 25980998
TI  - Practical application of new technologies for melanoma diagnosis: Part I.
      Noninvasive approaches.
AB  - Confirming a diagnosis of cutaneous melanoma requires obtaining a skin biopsy
      specimen. However, obtaining numerous biopsy specimens-which often happens in
      patients with increased melanoma risk-is associated with significant cost and
      morbidity. While some melanomas are easily recognized by the naked eye, many can
      be difficult to distinguish from nevi, and therefore there is a need and
      opportunity to develop new technologies that can facilitate clinical examination
      and melanoma diagnosis. In part I of this 2-part continuing medical education
      article, we will review the practical applications of emerging technologies for
      noninvasive melanoma diagnosis, including mobile (smartphone) applications,
      multispectral imaging (ie, MoleMate and MelaFind), and electrical impedance
      spectroscopy (Nevisense). 

PMID- 25980999
TI  - Practical application of new technologies for melanoma diagnosis: Part II.
      Molecular approaches.
AB  - The criterion standard for diagnosing cutaneous melanoma continues to be
      histologic examination. However, classifying some melanocytic lesions by
      conventional microscopy can be problematic if they exhibit some architectural or
      morphologic characteristics of both nevus and melanoma. Moreover, histologic
      appearance does not always predict biologic behavior. There is therefore a need
      and opportunity to develop new technologies that can facilitate the histologic
      diagnosis of melanoma and potentially help distinguish lesions with a lesser or
      greater risk of metastasis. In part II of this 2-part continuing medical
      education article, we will review the molecular technologies currently available
      for facilitating melanoma diagnosis, including comparative genomic hybridization,
      fluorescence in situ hybridization, and epidermal genetic retrieval. Our goal is
      to provide the clinician with an up to date understanding of these molecular
      approaches so that they can be applied to their management of challenging
      melanocytic lesions. 

PMID- 25981000
TI  - Sezary syndrome without erythroderma.
AB  - BACKGROUND: Sezary syndrome is a cutaneous T-cell lymphoma characterized by
      erythroderma and leukemic involvement. OBJECTIVE: We sought to define the
      clinical, biologic, and histopathologic features of Sezary syndrome without
      erythroderma. METHODS: Features of patients with Sezary syndrome and normal
      appearing skin or stage-T1 patches, fulfilling Sezary syndrome hematologic
      criteria and with histologically documented disease in normal-appearing skin were
      collected. Expression of Sezary syndrome molecular biomarkers in peripheral blood
      and skin lymphocytes were studied. RESULTS: Five women and 1 man (median age: 71
      years) were all referred for generalized pruritus. Four had no specific lesions;
      2 had T1-stage patches. Histologic examination of normal-appearing skin from all
      patients showed lesions compatible with Sezary syndrome. Peripheral blood
      lymphocytes from 3 of 4 patients tested strongly expressed PLS3, Twist-1, and
      KIR3DL2. All normal-appearing skin biopsy specimens expressed programmed death-1.
      Median follow-up was 9 years. Although no patient developed erythroderma, tumors,
      or abnormal lymph nodes, specific skin lesions appeared in all patients during
      follow-up. Only 1 death, unrelated to Sezary syndrome, occurred. LIMITATIONS:
      Retrospective design and small sample size are limitations. CONCLUSION: Sezary
      syndrome without erythroderma is a rare entity that may have a better prognosis
      than classic Sezary syndrome.

PMID- 25981001
TI  - Hematopoietic stem cell transplantation for primary cutaneous gammadelta T-cell
      lymphoma and refractory subcutaneous panniculitis-like T-cell lymphoma.
AB  - BACKGROUND: The panniculitic T-cell lymphomas (TCLs) comprise 2 distinct
      entities, alphabeta subcutaneous panniculitis-like TCL (SPTCL) and the gammadelta
      cutaneous TCLs with pannicular involvement primary cutaneous gammadelta (PCGD)
      TCL. Although outcomes for most patients with SPTCL are favorable, those with
      PCGD-TCLs generally have an inferior outcome, and treatment strategies have not
      been well defined. Allogeneic hematopoietic stem cell transplantation (HSCT) has
      been shown to be a potentially curative strategy in aggressive TCLs and in
      refractory and advanced-stage mycosis fungoides. OBJECTIVE: We sought to analyze
      the outcomes of HSCT for panniculitic cutaneous TCL. RESULTS: Fourteen patients
      (4 SPTCL, 10 PCGD-TCL) presented with primarily pannicular T-cell infiltrates.
      Seven patients underwent allogeneic HSCT from matched-related donors and matched
      unrelated donors of which 4 (57%) are alive (1 SPTCL, 3 PCGD-TCL) at 7.8, 6.9,
      6.2, and 0.25 years. Two patients underwent autologous HSCT (1 SPTCL, 1 PCGD-TCL)
      and both are alive at a median follow-up of 1.91 years. LIMITATIONS: This study
      is limited by its retrospective nature and small sample size because of the
      rarity of SPTCL and PCGD-TCL. CONCLUSION: Aggressive therapy followed by
      allogeneic HSCT is a promising treatment modality for patients with PCGD-TCL.

PMID- 25981002
TI  - Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy
      and safety of vismodegib in advanced BCC.
AB  - BACKGROUND: Primary analysis from the pivotal ERIVANCE BCC study resulted in
      approval of vismodegib, a Hedgehog pathway inhibitor indicated for treatment of
      adults with metastatic or locally advanced basal cell carcinoma (BCC) that has
      recurred after surgery or for patients who are not candidates for surgery or
      radiation. OBJECTIVE: An efficacy and safety analysis was conducted 12 months
      after primary analysis. METHODS: This was a multinational, multicenter,
      nonrandomized, 2-cohort study in patients with measurable and histologically
      confirmed locally advanced or metastatic BCC taking oral vismodegib (150 mg/d).
      Primary outcome measure was objective response rate (complete and partial
      responses) assessed by independent review facility. RESULTS: After 12 months of
      additional follow-up, median duration of exposure to vismodegib was 12.9 months.
      Objective response rate increased from 30.3% to 33.3% in patients with metastatic
      disease, and from 42.9% to 47.6% in patients with the locally advanced form.
      Median duration of response in patients with locally advanced BCC increased from
      7.6 to 9.5 months. No new safety signals emerged with extended treatment
      duration. LIMITATIONS: Limitations include low prevalence of advanced BCC and
      challenges of designing a study with heterogenous manifestations. CONCLUSION: The
      12-month update of the study confirms the efficacy and safety of vismodegib in
      management of advanced BCC.

PMID- 25981003
TI  - Two become one: Ethics in dermatologic surgery.

PMID- 25981004
TI  - Phototherapy in dermatology: A call for action.
AB  - Of the wide range of treatment modalities available to dermatologists, few
      possess the history, efficacy, and safety of phototherapy. It should be
      emphasized that dermatologists are the only group of physicians optimally trained
      and qualified to understand the medical indications of phototherapy.
      Phototherapy, recognized for its cost-effectiveness, should remain a
      consideration in patient treatment. Continued training and education in residency
      and thereafter is needed to maintain the proficiency of physicians. In addition,
      payors need continued education to ensure that insurance coverage of phototherapy
      is not a barrier for patients to access this therapy. To further improve and
      optimize the outcome, phototherapy research needs to be supported. 

PMID- 25981005
TI  - Skin cancer early detection information in popular US magazines (2000-2012).

PMID- 25981006
TI  - Generalized verrucosis and HPV-3 susceptibility associated with CD4 T-cell
      lymphopenia caused by inherited human interleukin-7 deficiency.

PMID- 25981007
TI  - The Africa Teledermatology Project: A retrospective case review of 1229
      consultations from sub-Saharan Africa.

PMID- 25981008
TI  - Treatment of folliculitis decalvans with photodynamic therapy: Results in 10
      patients.

PMID- 25981009
TI  - Depression of the frontal veins: A new clinical sign of frontal fibrosing
      alopecia.

PMID- 25981010
TI  - The efficacy of methotrexate for lymphomatoid papulosis.

PMID- 25981011
TI  - Association between psoriasis and neovascular age-related macular degeneration: A
      population-based study.

PMID- 25981012
TI  - Indoor tanning users' experiences with tanning salon direct to consumer
      marketing.

PMID- 25981013
TI  - Aspirin use and melanoma: A UCLA pilot study.

PMID- 25981016
TI  - Use of dermoscopy in the diagnosis of sebaceoma.

PMID- 25981017
TI  - Dermoscopy and reflectance confocal microscopy in verruciform xanthoma of the
      glans penis.

PMID- 25981018
TI  - Tape stripping: A very short-term follow-up procedure for suspicious black
      lesions.

PMID- 25981019
TI  - Using a hand-held black-light source instead of a Wood's lamp.

PMID- 25981020
TI  - Radiofrequency device for tick removal.

PMID- 25981021
TI  - Increasing utility of finasteride for frontal fibrosing alopecia.

PMID- 25981022
TI  - Use of a nonnarcotic antitussive for severe, treatment-resistant oral ulcers.

PMID- 25981023
TI  - Surgical pearl: A novel punch biopsy technique for diagnosing panniculitis.

PMID- 25981024
TI  - The running set-back dermal suture.

PMID- 25981025
TI  - Skin markings fixed with iodine: The surgical marking Gram stain.

PMID- 25981026
TI  - Is the current model for acne pathogenesis backwards?

PMID- 25981027
TI  - A note on normality.

PMID- 25981028
TI  - Reply to: "A note on normality".

PMID- 25981029
TI  - Melanoma in xeroderma pigmentosum type C children: Overrepresentation of
      desmoplastic type?

PMID- 25981030
TI  - IgE reactivity and survival probabilities in Sezary syndrome.

PMID- 25981031
TI  - Reply to: "IgE reactivity and survival probabilities in Sezary syndrome".

PMID- 25981032
TI  - Evidence on pseudoallergen-free diet for chronic urticaria.

PMID- 25981033
TI  - Response to: "Evidence on pseudoallergen-free diet for chronic urticaria".

PMID- 25981034
TI  - Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.
AB  - Accumulation of insoluble Tau protein aggregates and stereotypical propagation of
      Tau pathology through the brain are common hallmarks of tauopathies, including
      Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along
      connected neurons, but whether synaptic contacts between neurons are facilitating
      propagation has not been demonstrated. Using quantitative in vitro models, we
      demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not
      merely the close distance between the cells, enhance the propagation of Tau
      pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in
      an artificial neuronal network using microfluidic devices, synapses and synaptic
      activity are promoting neuronal Tau pathology propagation in parallel to the non
      synaptic mechanisms. Our work indicates that the physical presence of synaptic
      contacts between neurons facilitate Tau pathology propagation. These findings can
      have implications for synaptic repair therapies, which may turn out to have
      adverse effects by promoting propagation of Tau pathology. 

PMID- 25981035
TI  - Grass plants bind, retain, uptake, and transport infectious prions.
AB  - Prions are the protein-based infectious agents responsible for prion diseases.
      Environmental prion contamination has been implicated in disease transmission.
      Here, we analyzed the binding and retention of infectious prion protein (PrP(Sc))
      to plants. Small quantities of PrP(Sc) contained in diluted brain homogenate or
      in excretory materials (urine and feces) can bind to wheat grass roots and
      leaves. Wild-type hamsters were efficiently infected by ingestion of prion
      contaminated plants. The prion-plant interaction occurs with prions from diverse
      origins, including chronic wasting disease. Furthermore, leaves contaminated by
      spraying with a prion-containing preparation retained PrP(Sc) for several weeks
      in the living plant. Finally, plants can uptake prions from contaminated soil and
      transport them to aerial parts of the plant (stem and leaves). These findings
      demonstrate that plants can efficiently bind infectious prions and act as
      carriers of infectivity, suggesting a possible role of environmental prion
      contamination in the horizontal transmission of the disease. 

PMID- 25981036
TI  - Two independent mushroom body output circuits retrieve the six discrete
      components of Drosophila aversive memory.
AB  - Understanding how the various memory components are encoded and how they interact
      to guide behavior requires knowledge of the underlying neural circuits.
      Currently, aversive olfactory memory in Drosophila is behaviorally subdivided
      into four discrete phases. Among these, short- and long-term memories rely,
      respectively, on the gamma and alpha/beta Kenyon cells (KCs), two distinct
      subsets of the ~2,000 neurons in the mushroom body (MB). Whereas V2 efferent
      neurons retrieve memory from alpha/beta KCs, the neurons that retrieve short-term
      memory are unknown. We identified a specific pair of MB efferent neurons, named
      M6, that retrieve memory from gamma KCs. Moreover, our network analysis revealed
      that six discrete memory phases actually exist, three of which have been
      conflated in the past. At each time point, two distinct memory components
      separately recruit either V2 or M6 output pathways. Memory retrieval thus
      features a dramatic convergence from KCs to MB efferent neurons. 

PMID- 25981037
TI  - Cellular mechanisms underlying behavioral state-dependent bidirectional
      modulation of motor cortex output.
AB  - Neuronal activity in primary motor cortex (M1) correlates with behavioral state,
      but the cellular mechanisms underpinning behavioral state-dependent modulation of
      M1 output remain largely unresolved. Here, we performed in vivo patch-clamp
      recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet
      wakefulness and self-paced, voluntary movement. We show that L5B output neurons
      display bidirectional (i.e., enhanced or suppressed) firing rate changes during
      movement, mediated via two opposing subthreshold mechanisms: (1) a global
      decrease in membrane potential variability that reduced L5B firing rates
      (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in
      excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that
      elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished
      the bidirectional modulation of M1 output during movement and selectively
      impaired contralateral forelimb motor coordination. Together, our results provide
      a mechanism for how noradrenergic neuromodulation and network-driven input
      changes bidirectionally modulate M1 output during motor behavior. 

PMID- 25981038
TI  - Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and
      Glucose Homeostasis.
AB  - Insulin and insulin-like growth factor 1 (IGF-1) are major regulators of muscle
      protein and glucose homeostasis. To determine how these pathways interact, we
      generated mice with muscle-specific knockout of IGF-1 receptor (IGF1R) and
      insulin receptor (IR). These MIGIRKO mice showed >60% decrease in muscle mass.
      Despite a complete lack of insulin/IGF-1 signaling in muscle, MIGIRKO mice
      displayed normal glucose and insulin tolerance. Indeed, MIGIRKO mice showed
      fasting hypoglycemia and increased basal glucose uptake. This was secondary to
      decreased TBC1D1 resulting in increased Glut4 and Glut1 membrane localization.
      Interestingly, overexpression of a dominant-negative IGF1R in muscle induced
      glucose intolerance in MIGIRKO animals. Thus, loss of insulin/IGF-1 signaling
      impairs muscle growth, but not whole-body glucose tolerance due to increased
      membrane localization of glucose transporters. Nonetheless, presence of a
      dominant-negative receptor, even in the absence of functional IR/IGF1R, induces
      glucose intolerance, indicating that interactions between these receptors and
      other proteins in muscle can impair glucose homeostasis. 

PMID- 25981040
TI  - Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage
      in the Brain Dorsomedial Lineage Precursors.
AB  - In vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively
      poorly characterized. We study the Drosophila mushroom body (MB) axons, whose
      alpha and beta branches connect to different brain areas. We show that the Ryk
      family WNT5 receptor, DRL (derailed), which is expressed in the dorsomedial
      lineages, brain structure precursors adjacent to the MBs, is required for MB
      alpha branch axon guidance. DRL acts to capture and present WNT5 to MB axons
      rather than transduce a WNT5 signal. DRL's ectodomain must be cleaved and shed to
      guide alpha axons. DRL-2, another Ryk, is expressed within MB axons and functions
      as a repulsive WNT5 signaling receptor. Finally, our biochemical data support the
      existence of a ternary complex composed of the cleaved DRL ectodomain, WNT5, and
      DRL-2. Thus, the interaction of MB-extrinsic and -intrinsic Ryks via their common
      ligand acts to guide MB alpha axons. 

PMID- 25981039
TI  - A Primary Role for the Tsix lncRNA in Maintaining Random X-Chromosome
      Inactivation.
AB  - Differentiating pluripotent epiblast cells in eutherians undergo random X
      inactivation, which equalizes X-linked gene expression between the sexes by
      silencing one of the two X-chromosomes in females. Tsix RNA is believed to
      orchestrate the initiation of X-inactivation, influencing the choice of which X
      remains active by preventing expression of the antisense Xist RNA, which is
      required to silence the inactive-X. Here we profile X-chromosome activity in Tsix
      mutant (X(DeltaTsix)) mouse embryonic epiblasts, epiblast stem cells, and
      embryonic stem cells. Unexpectedly, we find that Xist is stably repressed on the
      X(DeltaTsix) in both sexes in undifferentiated epiblast cells in vivo and in
      vitro, resulting in stochastic X-inactivation in females despite Tsix
      heterozygosity. Tsix is instead required to silence Xist on the active-X as
      epiblast cells differentiate in both males and females. Thus, Tsix is not
      required at the onset of random X-inactivation; instead, it protects the active-X
      from ectopic silencing once X-inactivation has commenced. 

PMID- 25981041
TI  - Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila.
AB  - In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates
      transcription of period (per) and timeless (tim) in the evening. PER and TIM
      proteins then repress CLOCK (CLK) activity during the night. The pace of the
      oscillator depends upon post-translational regulation that affects both positive
      and negative components of the transcriptional loop. CLK protein is highly
      phosphorylated and inactive in the morning, whereas hypophosphorylated active
      forms are present in the evening. How this critical dephosphorylation step is
      mediated is unclear. We show here that two components of the STRIPAK complex, the
      CKA regulatory subunit of the PP2A phosphatase and its interacting protein STRIP,
      promote CLK dephosphorylation during the daytime. In contrast, the WDB regulatory
      PP2A subunit stabilizes CLK without affecting its phosphorylation state.
      Inhibition of the PP2A catalytic subunit and CKA downregulation affect daytime
      CLK similarly, suggesting that STRIPAK complexes are the main PP2A players in
      producing transcriptionally active hypophosphorylated CLK. 

PMID- 25981042
TI  - DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its
      Function Is Attenuated by Virus-Induced EGFR Activation.
AB  - RIG-I-mediated type I interferon (IFN) production and nuclease-mediated viral RNA
      degradation are essential for antiviral innate immune responses. DDX60 is an IFN
      inducible cytoplasmic helicase. Here, we report that DDX60 is a sentinel for both
      RIG-I activation and viral RNA degradation. We show that DDX60 is an upstream
      factor of RIG-I that activates RIG-I signaling in a ligand-specific manner. DDX60
      knockout attenuates RIG-I signaling and significantly reduces virus-induced type
      I IFN production in vivo. In addition, we show that DDX60 is involved in RIG-I
      independent viral RNA degradation. DDX60 and RIG-I adaptor MAVS double-knockout
      mice reveal a role for DDX60-dependent RNA degradation in antiviral responses.
      Several viruses induced DDX60 phosphorylation via epidermal growth factor
      receptor (EGFR), leading to attenuation of the DDX60 antiviral activities. Our
      results define DDX60 as a sentinel for cytoplasmic antiviral response, which is
      counteracted by virus-mediated EGF receptor activation. 

PMID- 25981043
TI  - Transmembrane Complexes of DAP12 Crystallized in Lipid Membranes Provide Insights
      into Control of Oligomerization in Immunoreceptor Assembly.
AB  - The membrane-spanning alpha helices of single-pass receptors play crucial roles
      in stabilizing oligomeric structures and transducing biochemical signals across
      the membrane. Probing intermolecular transmembrane interactions in single-pass
      receptors presents unique challenges, reflected in a gross underrepresentation of
      their membrane-embedded domains in structural databases. Here, we present two
      high-resolution structures of transmembrane assemblies from a eukaryotic single
      pass protein crystallized in a lipidic membrane environment. Trimeric and
      tetrameric structures of the immunoreceptor signaling module DAP12, determined to
      1.77-A and 2.14-A resolution, respectively, are organized by the same polar
      surfaces that govern intramembrane assembly with client receptors. We demonstrate
      that, in addition to the well-studied dimeric form, these trimeric and tetrameric
      structures are made in cells, and their formation is competitive with receptor
      association in the ER. The polar transmembrane sequences therefore act as primary
      determinants of oligomerization specificity through interplay between charge
      shielding and sequestration of polar surfaces within helix interfaces. 

PMID- 25981044
TI  - Involvement of Multiple Gene-Silencing Pathways in a Paramutation-like Phenomenon
      in Arabidopsis.
AB  - Paramutation is an epigenetic phenomenon that has been observed in a number of
      multicellular organisms. The epigenetically silenced state of paramutated alleles
      is not only meiotically stable but also "infectious" to active homologous
      alleles. The molecular mechanism of paramutation remains unclear, but components
      involved in RNA-directed DNA methylation (RdDM) are required. Here, we report a
      multi-copy pRD29A-LUC transgene in Arabidopsis thaliana that behaves like a
      paramutation locus. The silent state of LUC is induced by mutations in the DNA
      glycosylase gene ROS1. The silent alleles of LUC are not only meiotically stable
      but also able to transform active LUC alleles into silent ones, in the absence of
      ros1 mutations. Maintaining silencing at the LUC gene requires action of multiple
      pathways besides RdDM. Our study identified specific factors that are involved in
      the paramutation-like phenomenon and established a model system for the study of
      paramutation in Arabidopsis. 

PMID- 25981046
TI  - Non-invasive instant genotyping of fluorescently labelled transgenic mice.
AB  - Fluorescence proteins have been useful as genetic reporters for a wide range of
      applications in biomedical research and are frequently used for the analysis of
      transgene activity. Here, we show that expression levels of the ubiquitously
      expressed fluorescent proteins eGFP, mCherry, and tdTomato can be measured in
      transgenic mouse lines with random or targeted integrations. We identified the
      tail of the mouse as the tissue best suited for quantifying fluorescence
      intensity and show that expression levels in the tail correlate with gene dose.
      This allows for instant non-invasive determination of the genetic condition at
      the transgenic locus (hemizygous/heterozygous and homozygous), while
      simultaneously providing an objective comparison for transgene expression levels
      among different mouse lines. In summary, we demonstrate for the first time that
      the gene dose of a ubiquitously expressed fluorescence reporter can be reliably
      quantified and directly linked to the genotype of transgenic mice. Based on this
      information, animals with the appropriate genotype can be instantly selected
      without laborious analysis for establishing and breeding of new transgenic lines,
      reducing the number of "waste" animals. Furthermore, no tissue sampling is
      necessary, which is a significant refinement of genotyping procedures. Both
      aspects are important improvements for the genotyping of transgenic mice that
      follow the principles of the 3 Rs (reduction and refinement).

PMID- 25981045
TI  - Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors
      in the Evolution of Vif Anti-APOBEC3 Activity.
AB  - HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING
      ubiquitin ligase (CRL) complex as well as the non-canonical cofactor CBFbeta, to
      antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL
      complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To
      further study this phenomenon, we employed a comparative approach combining
      proteomic, biochemical, structural, and virological techniques to investigate Vif
      complexes across the lentivirus genus, including primate (HIV-1 and simian
      immunodeficiency virus macaque [SIVmac]) and non-primate (FIV, BIV, and MVV)
      viruses. We find that CBFbeta is completely dispensable for the activity of non
      primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no
      cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA), for
      stable CRL complex formation and anti-APOBEC3 activity. We propose modular
      conservation of Vif complexes allows for potential exaptation of functions
      through the acquisition of non-CRL-associated host cofactors while preserving
      anti-APOBEC3 activity. 

PMID- 25981047
TI  - Constitutive expression of Arabidopsis MYB transcription factor, AtMYB11, in
      tobacco modulates flavonoid biosynthesis in favor of flavonol accumulation.
AB  - KEY MESSAGE: Heterologous expression of AtMYB11 , a flavonol-specific
      transcription factor from Arabidopsis , in tobacco modulates flavonoid
      biosynthesis, however, with a lower efficiency as compared to its paralogs
      AtMYB12 and AtMYB111. Transcriptional regulation is the most important means for
      controlling flavonoid biosynthesis under temporal and spatial cues. In
      Arabidopsis, three functionally redundant MYB transcription factors (AtMYB11,
      AtMYB111 and AtMYB12) have been characterized as flavonol-specific regulators
      which positively modulate expression of biosynthetic genes involved in flavonol
      biosynthesis. Based on expression of AtMYB111 and AtMYB12 in heterologous
      systems, studies suggest that these transcription factors can be used to develop
      plants with enhanced flavonol biosynthesis. The potential of AtMYB11 to activate
      flavonol biosynthesis in a heterologous system has not yet been studied. In this
      study, the regulatory potential of AtMYB11 has been studied in Nicotiana tabacum
      by developing transgenic plants constitutively expressing AtMYB11. Our analysis
      using leaf and petal tissues of the transgenic plants indicates that AtMYB11
      enhances flavonol and chlorogenic acid (CGA) biosynthesis in tobacco through up
      regulation of the biosynthetic genes. Activation of flavonol biosynthesis in
      tobacco by AtMYB11 is not as pronounced as with AtMYB12 or AtMYB111. Taken
      together, these results reveal a differential regulatory mechanism in plants for
      modulating flavonol biosynthesis. This study demonstrated that AtMYB11 can be
      strategically used for enhancing the health beneficial flavonols in species other
      than Arabidopsis.

PMID- 25981048
TI  - Production of the dammarene sapogenin (protopanaxadiol) in transgenic tobacco
      plants and cultured cells by heterologous expression of PgDDS and CYP716A47.
AB  - KEY MESSAGE: Protopanaxadiol (PPD) is an aglycone of dammarene-type ginsenoside
      and has high medicinal values. In this work, we reported the PPD production in
      transgenic tobacco co-overexpressing PgDDS and CYP716A47. PPD is an aglycone of
      ginsenosides produced by Panax species and has a wide range of pharmacological
      activities. PPD is synthesized via the hydroxylation of dammarenediol-II (DD) by
      CYP716A47 enzyme. Here, we established a PPD production system via cell
      suspension culture of transgenic tobacco co-overexpressing the genes for PgDDS
      and CYP716A47. The concentration of PPD in transgenic tobacco leaves was 2.3-5.7
      ug/g dry weight (DW), depending on the transgenic line. Leaf segments were
      cultured on medium with various types of hormones to induce callus. Auxin
      treatment, particularly 2,4-D, strongly enhanced the production of DD (783.8 ug
      g(-1) DW) and PPD (125.9 ug g(-1) DW). Treatment with 2,4-D enhanced the
      transcription of the HMG-Co reductase (HMGR) and squalene epoxidase genes. PPD
      production reached 166.9 and 980.9 ug g(-1) DW in a 250-ml shake flask culture
      and in 5-l airlift bioreactor culture, respectively.

PMID- 25981049
TI  - Biological 18[F]-FDG-PET image-guided dose painting by numbers for painful
      uncomplicated bone metastases: A 3-arm randomized phase II trial.
AB  - BACKGROUND: Antalgic radiotherapy for bone metastases might be improved by
      implementing biological information in the radiotherapy planning using (18)F-FDG
      PET-CT based dose painting by numbers (DPBN). MATERIALS AND METHODS: Patients
      with uncomplicated painful bone metastases were randomized (1:1:1) and blinded to
      receive either 8Gy in a single fraction with conventionally planned radiotherapy
      (arm A) or 8Gy in a single fraction with DPBN (dose range between 610Gy and 10Gy)
      (arm B) or 16Gy in a single fraction with DPBN (dose range between 1410Gy and
      18Gy) (arm C). The primary endpoint was overall pain response at 1month. The
      phase II trial was designed to select the experimental arm with sufficient
      promise of efficacy to continue to a phase III trial. RESULTS: Forty-five
      patients were randomized. Eight (53%), 12 (80%) and 9 patients (60%) had an
      overall response to treatment in arm A, B and C, respectively. The estimated odds
      ratio of overall response for arm B vs. A is 3.5 (95% CI: 0.44-17.71, p=0.12).
      The estimated odds ratio of arm C vs. A is 1.31 (95% CI: 0.31-5.58, p=0.71).
      CONCLUSION: A single fraction of 8Gy with DPBN will be further evaluated in a
      phase III-trial.

PMID- 25981050
TI  - Clipping of tumour resection margins allows accurate target volume delineation in
      head and neck cancer adjuvant radiation therapy.
AB  - BACKGROUND: Accurate tumour bed localisation is a key requirement for adjuvant
      radiotherapy. A new procedure is described for head and neck cancer treatment
      that improves tumour bed localisation using titanium clips. MATERIALS AND
      METHODS: Following complete local excision of the primary tumour, the tumour bed
      was marked with titanium clips. Preoperative gross target volume (GTV) and
      postoperative tumour bed were examined and the distances between the centres of
      gravity were evaluated. RESULTS: 49 patients with squamous cell carcinoma of the
      oral cavity were prospectively enrolled in this study. All patients underwent
      tumour resection, neck lymph node dissection and defect reconstruction in one
      stage. During surgery, 7-49 clips were placed in the resection cavity. Surgical
      clip insertion was successful in 88% (n=43). Clip identification and tumour bed
      delineation was successful in all 43 patients. The overall distance between the
      centres of gravity of the preoperative tumour extension to the tumour bed was
      0.9cm. A significant relationship between the preoperative tumour extension and
      the postoperative tumour bed volume could be demonstrated. CONCLUSION: We
      demonstrate a precise delineation of the former tumour cavity. Improvements in
      tumour bed delineation allow an increase of accuracy for adjuvant treatment.

PMID- 25981051
TI  - Palliative radiotherapy (PRT) during the last month of life: A constant sorrow
      even in a dedicated PRT facility with research focus on this endpoint.

PMID- 25981052
TI  - The optimal utilization proportion of external beam radiotherapy in European
      countries: An ESTRO-HERO analysis.
AB  - BACKGROUND AND PURPOSE: The absolute number of new cancer patients that will
      require at least one course of radiotherapy in each country of Europe was
      estimated. MATERIAL AND METHODS: The incidence and relative frequency of cancer
      types from the year 2012 European Cancer Observatory estimates were used in
      combination with the population-based stage at diagnosis from five cancer
      registries. These data were applied to the decision trees of the evidence-based
      indications to calculate the Optimal Utilization Proportion (OUP) by tumour site.
      RESULTS: In the minimum scenario, the OUP ranged from 47.0% in the Russian
      Federation to 53.2% in Belgium with no clear geographical pattern of the
      variability among countries. The impact of stage at diagnosis on the OUP by
      country was rather limited. Within the 24 countries where data on actual use of
      radiotherapy were available, a gap between optimal and actual use has been
      observed in most of the countries. CONCLUSIONS: The actual utilization of
      radiotherapy is significantly lower than the optimal use predicted from the
      evidence based estimates in the literature. This discrepancy poses a major
      challenge for policy makers when planning the resources at the national level to
      improve the provision in European countries.

PMID- 25981053
TI  - The increase in tumor oxygenation under carbogen breathing induces a decrease in
      the uptake of [(18)F]-fluoro-deoxy-glucose.
AB  - We investigated the impact of oxygenation status (measured by EPR oximetry) on
      the uptake of (18)F-FDG (measured by PET) in two different tumor models during a
      carbogen breathing challenge. We observed a significant drop in (18)F-FDG uptake
      under carbogen breathing that suggests a rapid metabolic adaptation to the oxygen
      environment. 

PMID- 25981054
TI  - A comparison of two clinical correlation models used for real-time tumor tracking
      of semi-periodic motion: A focus on geometrical accuracy in lung and liver cancer
      patients.
AB  - PURPOSE: A head-to-head comparison of two clinical correlation models with a
      focus on geometrical accuracy for internal tumor motion estimation during real
      time tumor tracking (RTTT). METHODS AND MATERIALS: Both the CyberKnife (CK) and
      the Vero systems perform RTTT with a correlation model that is able to describe
      hysteresis in the breathing motion. The CK dual-quadratic (DQ) model consists of
      two polynomial functions describing the trajectory of the tumor for inhale and
      exhale breathing motion, respectively. The Vero model is based on a two
      dimensional (2D) function depending on position and speed of the external
      breathing signal to describe a closed-loop tumor trajectory. In this study, 20 s
      of internal motion data, using an 11 Hz (on average) full fluoroscopy (FF)
      sequence, was used for training of the CK and Vero models. Further, a subsampled
      set of 15 internal tumor positions (15p) equally spread over the different phases
      of the breathing motion was used for separate training of the CK DQ model. Also a
      linear model was trained using 15p and FF tumor motion data. Fifteen liver and
      lung cancer patients, treated on the Vero system with RTTT, were retrospectively
      evaluated comparing the CK FF, CK 15p and Vero FF models using an in-house
      developed simulator. The distance between estimated target position and the tumor
      position localized by X-ray imaging was measured in the beams-eye view (BEV) to
      calculate the 95th percentile BEV modeling errors (ME(95,BEV)). Additionally, the
      percentage of ME(95,BEV) smaller than 5 mm (P(5mm)) was determined for all
      correlation models. RESULTS: In general, no significant difference (p>0.05,
      paired t-test) was found between the CK FF and Vero models. Based on patient
      specific evaluation of the geometrical accuracy of the linear, CK DQ and Vero
      correlation models, no statistical necessity (p>0.05, two-way ANOVA) of including
      hysteresis in correlation models was proven, although during inhale breathing
      motion, the linear model resulted in a decreased P(5mm) with 5-6% compared to
      both the DQ CK and Vero models. CONCLUSION: Dual-quadratic CyberKnife and 2D Vero
      correlation models were interchangeable in terms of geometrical accuracy with the
      CK linear ME(95,BEV)=4.1 mm, CK dual-quadratic ME(95,BEV)=3.9 mm and Vero
      ME(95,BEV)=3.7 mm, when modeled with FF sequence. CK DQ modeling based on 15p
      acquired in 20 s may lead to problems for internal motion estimation.

PMID- 25981055
TI  - Online Information Searches and Help Seeking for Mental Health Problems in Urban
      China.
AB  - In recent years, the Internet has emerged as an alternative information source on
      mental health problems. Yet, the profile of the typical Internet help seeker is
      to be determined. Based on data from a household survey of 2558 Beijing
      residents, the study investigates online information searches and help seeking
      for mental health problems. Multinomial logistic regressions are estimated for
      respondents' access to the Internet, and mental-health-related information
      searches and help seeking on the Internet for the whole community sample and the
      most psychologically distressed subsample. The study identifies a digital divide
      in online help seeking for mental health issues based on age, migration and hukou
      status, and socio-economic factors. Youth and high socio-economic status are
      significant predictors of Internet access and use. Among the whole community
      sample, rural-to-urban migrants are less likely to have access to the Internet
      and search information or seek help online. Among the most psychologically
      distressed subsample, urban-to-urban migrants are significantly more likely to
      have access to the Internet and search information or seek help online. Given the
      shortage of mental health professionals in China, online information
      dissemination and guided self-help, if properly designed, could offer a means to
      reach large numbers of individuals in a cost-effective manner.

PMID- 25981056
TI  - Perception and discrimination of movement and biological motion patterns in fish.
AB  - Vision is of primary importance for many fish species, as is the recognition of
      movement. With the exception of one study, assessing the influence of conspecific
      movement on shoaling behaviour, the perception of biological motion in fish had
      not been studied in a cognitive context. The aim of the present study was
      therefore to assess the discrimination abilities of two teleost species in regard
      to simple and complex movement patterns of dots and objects, including biological
      motion patterns using point and point-light displays (PDs and PLDs). In two
      alternative forced-choice experiments, in which choosing the designated positive
      stimulus was food-reinforced, fish were first tested in their ability to
      distinguish the video of a stationary black dot on a light background from the
      video of a moving black dot presented at different frequencies and amplitudes.
      While all fish succeeded in learning the task, performance declined with
      decreases in either or both parameters. In subsequent tests, cichlids and
      damselfish distinguished successfully between the videos of two dots moving at
      different speeds and amplitudes, between two moving dot patterns (sinus vs.
      expiring sinus) and between animated videos of two moving organisms (trout vs.
      eel). Transfer tests following the training of the latter showed that fish were
      unable to identify the positive stimulus (trout) by means of its PD alone,
      thereby indicating that the ability of humans to spontaneously recognize an
      organism based on its biological motion may not be present in fish. All
      participating individuals successfully discriminated between two PDs and two PLDs
      after a short period of training, indicating that biological motions presented in
      form of PLDs are perceived and can be distinguished. Results were the same for
      the presentation of dark dots on a light background and light dots on a dark
      background. 

PMID- 25981057
TI  - Assessment of carotid plaque composition using fast-kV switching dual-energy CT
      with gemstone detector: comparison with extracorporeal and virtual histology
      intravascular ultrasound.
AB  - INTRODUCTION: The present study compares the applicability of CT carotid plaque
      imaging using effective Z maps using gemstone spectral imaging (GSI) with that of
      conventional extracorporeal carotid ultrasound (US) and virtual histology
      intravascular ultrasound (VH-IVUS). METHODS: We assessed stenosis in 31 carotid
      arteries of 30 patients. All patients underwent carotid CTA using GSI (Discovery
      CT750 HD, GE Healthcare). US and IVUS were examined with 25 and 8 vessels,
      respectively. We compared the effective Z values at noncalcified carotid plaque
      with the plaque components identified by US. We defined the plaque with low or
      low to iso intensity on US as vulnerable plaque and the plaque with iso, iso to
      high, and high intensity on US as stable plaque. We also performed visual
      assessment of color-coded effective Z maps in comparison with VH-IVUS and
      compared effective Z values with plaque components generated by VH-IVUS. RESULTS:
      The effective Z values at noncalcified carotid plaque were significantly lower
      for a group with vulnerable plaque, than with stable plaque on US (p < 0.05).
      Receiver operating curve analysis showed that AUC of effective Z values was 0.882
      concerning the differentiation of these two groups on US. The interpretation of
      color-coded effective Z maps was essentially compatible with that of VH-IVUS for
      carotid plaque in all vessels. Effective Z values at noncalcified plaque showed
      significant negative correlation with the areas of fibro-fatty components
      generated by VH-IVUS (rho = -0.874, p < 0.05). CONCLUSION: Effective Z maps
      generated by GSI can detect vulnerable carotid plaque materials.

PMID- 25981058
TI  - Epidemiological study of onychomycosis in older adults with onychodystrophy.
AB  - AIM: To identify the prevalence of onychomycosis and epidemiological features in
      older adults (>65%) with toenail onychodystrophy. In particular, the aim of the
      study was to analyze risk factors/protective factors, clinical manifestations,
      comorbidities and etiological agents. METHODS: A prospective study was carried
      out from February 2012 to May 2012 at San Martino-IST of Genoa, Italy. The
      inclusion criteria for enrolment were the presence of onychodystrophy of one or
      more toenails and age >65 years. The exclusion criteria were systemic/topical
      antifungal treatments in the previous 6 months, drilling of the nail plate in the
      previous 6 months and a specialist's diagnosis or suspicion of onychomycosis. A
      database was created for the patients' anamnesis, the clinics and testing
      results. Several statistical analyses were carried out. RESULTS: A total of 100
      patients fulfilled the inclusion criteria. A total of 35 cases had positive
      results, and the etiological agent was isolable in 14 cases. The most represented
      was Trichophyton mentagrophytes followed by Trichophyton rubrum and others.
      Multivariate logistic regression analysis showed the significant roles of sex and
      diabetes as risk factors, and the use of statins as a protective factor.
      CONCLUSIONS: Onychomycosis has a high prevalence in older adults with
      onychodystrophy. It is important not to overlook onychodystrophy, and to carry
      out laboratory testing to exclude a fungal infection. In fact, as older patients
      often cannot undergo systemic antifungal therapies, it is fundamental to treat
      them early and avoid the spread of infection.

PMID- 25981059
TI  - "Discovery and development of new anticancer drugs inspired from natural product
      leads" part 1.

PMID- 25981060
TI  - Increasing stringiness of low-fat mozzarella string cheese using polysaccharides.
AB  - When fat content of pasta filata cheese is lowered, a loss of fibrous texture
      occurs and low-fat (LF) mozzarella cheese loses stringiness, making it unsuitable
      for the manufacture of string cheese. We investigated the use of various
      polysaccharides that could act as fat mimetics during the stretching and
      extruding process to aid in protein strand formation and increase stringiness.
      Low-fat mozzarella cheese curd was made, salted, and then 3.6-kg batches were
      heated in hot (80 degrees ) 5% brine, stretched, and formed into a homogeneous
      mass. Hot (80 degrees C) slurries of various polysaccharides were then mixed with
      the hot cheese and formed into LF string cheese using a small piston-driven
      extruder. Polysaccharides used included waxy corn starch, waxy rice starch,
      instant tapioca starch, polydextrose, xanthan gum, and guar gum. Adding starch
      slurries increased cheese moisture content by up to 1.6% but was not effective at
      increasing stringiness. Xanthan gum functioned best as a fat mimetic and produced
      LF string cheese that most closely visually resembled commercial string cheese
      made using low-moisture part skim (LMPS) mozzarella cheese without any increase
      in moisture content. Extent of stringiness was determined by pulling apart the
      cheese longitudinally and observing size, length, and appearance of individual
      cheese strings. Hardness was determined using a modified Warner-Bratzler shear
      test. When LF string cheese was made using a 10% xanthan gum slurry added at ~1%,
      increased consumer flavor liking was observed, with scores after 2wk of storage
      of 6.44 and 6.24 compared with 5.89 for the LF control cheese; although this was
      lower than an LMPS string cheese that scored 7.27. The 2-wk-old LF string cheeses
      containing xanthan gum were considered still slightly too firm using a just-about
      right (JAR) test, whereas the LMPS string cheese was considered as JAR for
      texture. With further storage up to 8wk, all of the LF string cheeses softened
      (JAR score was closer to 3.0); however, much of the stringiness of the LF string
      cheeses was also lost during storage. We have demonstrated the potential
      feasibility of increasing stringiness in LF string cheese using polysaccharides
      with xanthan gum, although further research is needed to develop quantitative
      methodology for measuring stringiness and to maintain stringiness through the
      extended refrigerated shelf life needed for string cheese. 

PMID- 25981061
TI  - Milk yield differences between 1* and 4* milking are associated with changes in
      mammary mitochondrial number and milk protein gene expression, but not mammary
      cell apoptosis or SOCS gene expression.
AB  - Milking frequency is known to affect milk production and lactation persistence in
      dairy cows. Despite this, the mechanisms underlying this effect are only
      partially understood. Previous work in dairy cows examining increases in milk
      yield due to increased milking frequency have identified changes in apoptosis and
      expression of genes regulating cytokine signaling. In addition, changes in
      mitochondrial biogenesis and function have been suggested to play a role during
      the lactation cycle in regulating milk production. The goal of this study was to
      test the hypothesis that, when maintained over an entire lactation, extreme
      differences in milking frequency would be reflected in differences in apoptosis,
      mammary mitochondrial number, and the mammary expression of genes known to
      inhibit cytokine signaling. Primiparous Holstein cows (n=6) were assigned to the
      study 40d before parturition after which 1 udder half was milked once daily (1*)
      and the other 4 times daily (4*) Mammary biopsies were collected at 15, 60, 120,
      and 230d of lactation. Average milk yield from the 4* side was 3 times higher
      than from the 1* side. Analysis of milk composition revealed that protein,
      lactose, and solids-not-fat percentages were lower in 1* than 4* udder halves.
      Mammary cell apoptosis was not affected by milking frequency. Mammary cell
      mitochondrial number, as estimated by succinate dehydrogenase staining, was
      higher in early lactation, decreasing as days in milk increased, and with
      increased milking frequency. Although mammary expression of alpha-lactalbumin
      (LALBA) and beta-casein (CSN2) was significantly increased in 4* glands, the
      expression of suppressors of cytokine signaling were similar between 1*- and 4*
      milked halves. These results support the conclusion that changes in milk
      production in response to extreme differences in milking frequency may be related
      to alterations in mitochondrial number and lactose synthesis, but not apoptosis. 

PMID- 25981063
TI  - Effects of nisin on Staphylococcus aureus count and physicochemical properties of
      Minas Frescal cheese.
AB  - The aim of this work was to evaluate the effects of nisin on in vitro and in situ
      Staphylococcus aureus counts. For in vitro experiment, milk was inoculated with
      5.0 log cfu.mL(-1) of S. aureus and nisin was added at concentrations of 0, 100,
      200, 400, and 500 IU mL(-1). The main effect of the bacteriocin was lag phase
      extension from 0h, for 0 and 100 IU.mL(-1) to 8h, when 200, 400, and 500 IU.mL(
      1) of nisin were used; however, log phase was not affected. Microbial growth rate
      was found to be exponential and around 0.11 log cfu.mL(-1).h(-1) for all
      treatments. For in situ experiments, 0, 400, and 500 IU.mL(-1) of nisin were
      directly added to pasteurized milk previously inoculated with 5.0 log cfu.g(-1)
      of S. aureus. Milk, curd, and whey were analyzed to S. aureus counts. Nisin at
      concentration of 500 IU.mL(-1) was able to reduce S. aureus count in curd and
      whey, demonstrating nisin partition between both phases. Throughout storage at 4
      degrees C, S. aureus count increased for all treatments, but the bacterial grew
      slower when nisin was added in both concentrations, maintaining S. aureus count
      about 1.5 log cycles lower than the control, despite abusive initial S. aureus
      count. Therefore, nisin seems to play an important role in reducing S. aureus
      initial count in cheese made with highly contaminated milk. Nisin showed
      potential to be used as an additional, important hurdle to improve Minas Frescal
      cheese safety, without replacing good manufacturing practices. 

PMID- 25981062
TI  - Performance, bioenergetic status, and indicators of oxidative stress of
      environmentally heat-loaded Holstein cows in response to diets inducing milk fat
      depression.
AB  - Effects of grain type and dietary oil supplement on production performance,
      energy balance, metabolic heat production, and markers of liver function of heat
      loaded lactating dairy cows were evaluated using 8 multiparous Holstein cows
      (77.0d in milk) in a duplicated 4*4 Latin square design with a 2*2 factorial
      arrangement of treatments. Experimental diets contained either ground barley or
      ground corn supplemented with either fish oil or soybean oil at 2% of dietary dry
      matter. Mean daily maximum temperature, minimum relative humidity, and maximum
      temperature-humidity index were 35.3 degrees C, 11.3%, and 77.0, respectively.
      Dietary treatment did not affect rectal temperature (38.9 degrees C), but
      respiration rate tended to decrease in cows fed fish oil versus soybean oil. Dry
      matter intake decreased for the fish oil-supplemented diets (21.1 vs. 24.3kg/d),
      which was negatively correlated with plasma concentrations of alkaline
      phosphatase (r=-0.45; n=32) and malondialdehyde (r=-0.26; n=32). Actual milk
      yield (41.9kg/d) and energy-corrected milk yield (36.6kg/d) were not affected by
      grain type, whereas feeding fish oil decreased milk yield as compared with
      soybean oil (40.4 vs. 43.4kg/d). Milk fat depression occurred in all dietary
      treatments, especially when cows were fed fish oil because of the presence of
      polyunsaturated FA in the diets. trans-10 C18:1 was negatively correlated with
      milk fat yield (r=-0.38; n=32). Daily milk cis-9,trans-11 C18:2 secretion was
      29.6% less in cows fed barley- versus corn-based diets but 31.8% greater in cows
      fed fish oil as compared with cows fed soybean oil. Because of a lower dry matter
      intake, metabolic heat production was decreased in cows fed fish oil relative to
      cows fed soybean oil. Although feeding fish oil versus soybean oil decreased net
      energy for both maintenance and lactation, net energy balance remained unchanged
      across treatments. In vivo plasma lipoperoxidation was greater in cows fed fish
      oil versus soybean oil, which substantiated increased susceptibility of plasma
      lipoperoxidation when cows were fed fish oil. Plasma concentration of
      malondialdehyde was positively correlated with plasma aspartate aminotransferase
      (r=0.38; n=32), which is an indicator of liver function in heat-loaded cows.
      Results suggest that in heat-loaded cows fed diets supplemented with soybean oil
      versus fish oil, biosynthesis in the mammary gland was prioritized over anabolism
      and oxidation in peripheral adipose and muscle tissues regardless of type of
      grain used. 

PMID- 25981064
TI  - Carbon footprint of dairy goat milk production in New Zealand.
AB  - The aim of this study was to assess the cradle-to-farm gate carbon footprint of
      indoor and outdoor dairy goat farming systems in New Zealand, identifying
      hotspots and discussing variability and methodology. Our study was based on the
      International Organization for Standardization standards for life cycle
      assessment, although only results for greenhouse gas emissions are presented. Two
      functional units were included: tonnes of CO2-equivalents (CO2e) per hectare (ha)
      and kilograms of CO2e per kilogram of fat- and protein-corrected milk (FPCM). The
      study covered 5 farms, 2 farming systems, and 3yr. Two methods for the
      calculation of enteric methane emissions were assessed. The Lassey method, as
      used in the New Zealand greenhouse gas inventory, provided a more robust estimate
      of emissions from enteric fermentation and was used in the final calculations.
      The alternative dry matter intake method was shown to overestimate emissions due
      to use of anecdotal assumptions around actual consumption of feed. Economic
      allocation was applied to milk and co-products. Scenario analysis was performed
      on the allocation method, nitrogen content of manure, manure management, and
      supplementary feed choice. The average carbon footprint for the indoor farms
      (n=3) was 11.05 t of CO2e/ha and 0.81kg of CO2e/kg of FPCM. For the outdoor farms
      (n=2), the average was 5.38 t of CO2e/ha and 1.03kg of CO2e/kg of FPCM. The
      average for all 5 farms was 8.78 t of CO2e/ha and 0.90kg of CO2e/kg of FPCM. The
      results showed relatively high variability due to differences in management
      practices between farms. The 5 farms covered 10% of the total dairy goat farms
      but may not be representative of an average farm. Methane from enteric
      fermentation was a major emission source. The use of supplementary feed was
      highly variable but an important contributor to the carbon footprint. Nitrous
      oxide can contribute up to 18% of emissions. Indoor goat farming systems produced
      milk with a significantly higher carbon footprint per area of land farmed
      compared with outdoor farming systems, although the 2 systems were not
      significantly different when results were expressed per kilogram of FPCM, at
      0.81kg CO2e and 1.03kg CO2e per kg of FPCM, respectively. Both systems had
      footprints less than other reported dairy goat carbon footprints and on par with
      those for New Zealand dairy cows. The methodology used to determine enteric
      methane is important for an accurate and meaningful assessment. The choice of
      manure management system and supplementary feed can substantially affect the
      carbon footprint. 

PMID- 25981065
TI  - Microbiological shelf life at different temperatures and fate of Listeria
      monocytogenes and Escherichia coli inoculated in unflavored and strawberry
      yogurts.
AB  - Three different trials were performed on unflavored and strawberry yogurts
      produced in a small-scale dairy plant. In the first trial, the microbiological
      shelf life of the products was evaluated at 4, 8, and 20 degrees C. At 4 degrees
      C the product showed low total viable counts until the end of the trial (d
      35=3.0+/-0.7 and 1.5+/-0.0 log cfu/g in unflavored and strawberry yogurt,
      respectively). The loads were lower in strawberry yogurt at 4 degrees C compared
      with unflavored yogurt because of the antimicrobial activity exerted by potassium
      sorbate present in the fruit puree added. Yeasts were confirmed to be the
      specific spoilage agents of this product, reaching rapidly high loads with
      thermal abuse (5.9-7.4 log cfu/g at d 18). In the second trial, Escherichia coli
      and especially Listeria monocytogenes added at 2 concentrations (2 and 5 log
      cfu/g) showed a rapid decrease in both types thanks to the acidic conditions
      provided by the products, but L. monocytogenes was very resistant; its presence
      was always detected until the end of the period considered (d 68). In the third
      trial, no statistically significant differences were detected between wild and
      acid-adapted strains of L. monocytogenes added to the products, due to the quick
      adaptation that probably occurred after inoculation. 

PMID- 25981066
TI  - Acid stress suggests different determinants for polystyrene and HeLa cell
      adhesion in Lactobacillus casei.
AB  - Adhesion has been regarded as one of the basic features of probiotics. The aim of
      this study was to investigate the influence of acid stress on the functional
      properties, such as hydrophobicity, adhesion to HeLa cells, and composition of
      membrane fatty acids, of Lactobacillus probiotics strains. Two strains of
      Lactobacillus casei were used. Adhesion on polystyrene, hydrophobicity,
      epithelial cells adhesion, and fatty acids analysis were evaluated. Our results
      showed that the membrane properties such as hydrophobicity and fatty acid
      composition of stressed strains were significantly changed with different pH
      values. However, we found that acid stress caused a change in the proportions of
      unsaturated and saturated fatty acid. The ratio of saturated fatty acid to
      unsaturated fatty acids observed in acid-stressed Lactobacillus casei cells was
      significantly higher than the ration in control cells. In addition, we observed a
      significant decrease in the adhesion ability of these strains to HeLa cells and
      to a polystyrene surface at low pH. The present finding could first add new
      insight about the acid stress adaptation and, thus, enable new strategies to be
      developed aimed at improving the industrial performance of this species under
      acid stress. Second, no relationship was observed between changes in membrane
      composition and fluidity induced by acid treatment and adhesion to biotic and
      abiotic surfaces. In fact, the decrease of cell surface hydrophobicity and the
      adhesion ability to abiotic surface and the increase of the capacity of adhesion
      to biotic surface demonstrate that adhesive characteristics will have little
      relevance in probiotic strain-screening procedures. 

PMID- 25981067
TI  - Short communication: Protease activity measurement in milk as a diagnostic test
      for clinical mastitis in dairy cows.
AB  - Due to the increasing use of automated milking systems, automated detection of
      clinical mastitis is becoming more important. Various in- or on-line diagnostic
      tests are in use, but generally suffer from false mastitis alerts. In this study,
      we explored a new diagnostic approach based on measurement of protease activity
      using fluorogenic protease substrates, which can be performed on site, at high
      speed, and at low costs. Samples from cows with clinical mastitis submitted for
      bacteriological culture at the University Farm Animal Practice were collected
      during several months and kept at -20 degrees C until protease activity
      measurement. A reference set of milk samples from clinically healthy cows were
      collected on 9 different farms and were tested for protease activity directly and
      after freezing at -20 degrees C to allow for comparison with the samples from
      clinical cases. The protease activity in mastitic milk samples was significantly
      higher than in samples from healthy animals. Based on 71 clinical mastitis
      samples and 180 milk samples from clinically healthy quarters, the area under the
      receiver-operating characteristic curve was estimated to be between 0.88 and
      0.90, and at a threshold of 38 fluorescence per minute the test had a specificity
      of 0.99 at a sensitivity of 0.58. Protease activity measured in fresh milk from
      clinically healthy cows was significantly associated with somatic cell count and
      parity, but not with electrical conductivity, whereas protease activity in milk
      that had been frozen was statistically significantly associated with all 3
      parameters. This study indicates that protease activity measurement as a stand
      alone test can be used for detecting mastitis samples, using milk samples that
      have been frozen. Because protease activity acts in part on a different
      biological mechanism than somatic cell count or electrical conductivity, this
      test may increase the accuracy of mastitis diagnosis in combination with
      currently available in- or on-line tests in automated milking systems. 

PMID- 25981068
TI  - Cow- and herd-level risk factors for on-farm mortality in Midwest US dairy herds.
AB  - The objectives of this study were to describe on-farm mortality and to
      investigate cow- and herd-level risk factors associated with on-farm mortality in
      Midwest US dairy herds using lactation survival analysis. We analyzed a total of
      approximately 5.9 million DHIA lactation records from 10 Midwest US states from
      January 2006 to December 2010. The cow-level independent variables used in the
      models were first test-day milk yield, milk fat percent, milk protein percent,
      fat-to-protein ratio, milk urea nitrogen, somatic cell score, previous dry
      period, previous calving interval, stillbirth, calf sex, twinning, calving
      difficulty, season of calving, parity, and breed. The herd-level variables
      included herd size, calving interval, somatic cell score, 305-d mature-equivalent
      milk yield, and herd stillbirth percentage. Descriptive analysis showed that
      overall cow-level mortality rate was 6.4 per 100 cow-years and it increased from
      5.9 in 2006 to 6.8 in 2010. Mortality was the primary reason of leaving the herd
      (19.4% of total culls) followed by reproduction (14.6%), injuries and other
      (14.0%), low production (12.3%), and mastitis (10.5%). Risk factor analysis
      showed that increased hazard for mortality was associated with higher fat-to
      protein ratio (>1.6 vs. 1 to 1.6), higher milk fat percent, lower milk protein
      percent, cows with male calves, cows carrying multiple calves, higher milk urea
      nitrogen, increasing parity, longer previous calving interval, higher first test
      day somatic cell score, increased calving difficulty score, and breed (Holstein
      vs. others). Decreased hazard for mortality was associated with higher first test
      day milk yield, higher milk protein, and shorter dry period. For herd-level
      factors, increased hazard for mortality was associated with increased herd size,
      increased percentage of stillbirths, higher somatic cell score, and increased
      herd calving interval. Cows in herds with higher milk yield had lower mortality
      hazard. Results of the study indicated that first test-day records, especially
      those indicative of negative energy balance in cows, could be helpful to identify
      animals at high risk for mortality. Higher milk yield per cow did not have a
      negative association with mortality. In addition, the association between herd
      level factors and mortality indicated that management quality could be an
      important factor in lowering on-farm mortality, thereby improving cow welfare. 

PMID- 25981069
TI  - Inbreeding and crossbreeding parameters for production and fertility traits in
      Holstein, Montbeliarde, and Normande cows.
AB  - Breed differences and nonadditive genetic effects for milk production traits,
      somatic cell score (SCS), conception rate (CR), and days to first service (DFS)
      were estimated for Holstein * Montbeliarde and Holstein * Normande crossbreds,
      using an animal model adapted from the French genetic evaluation and extended to
      across-breed analysis. Inbreeding and breed differences were estimated from all
      purebred recorded cows. Only records from 1,137 herds with Holstein *
      Montbeliarde crossbred cows and from 1,033 herds with Holstein * Normande
      crossbred cows were used to estimate crossbreeding parameters. In these herds,
      crossbred cows represented about 13% of the total number of recorded animals
      compared with <1% when all herds were considered. Compared with the Montbeliarde
      and Normande breeds, the Holstein breed was genetically superior for production
      [+951kg and +2,444kg for 305-d mature-equivalent (305ME) milk, +40kg and +102kg
      for 305ME fat, +17kg and +54kg for 305ME protein, respectively] and inferior for
      fertility traits (-12 and -9% for CR, respectively). Inbreeding depression caused
      loss of yield for production traits (from -32 to -41kg of 305ME milk, -1.4 to 
      1.7kg of 305ME fat, and -1.1 to -1.3kg of 305ME protein per inbreeding
      percentage), a small increase in SCS (+0.001 to 0.006) and DFS (+0.12d), and a
      decrease in CR (-0.27 to -0.44%). Favorable heterosis effects were found for all
      traits (+494 to 524kg of 305ME milk, +21 to 22kg of 305ME fat, +15 to 16kg of
      305ME protein, -0.05 to -0.04 SCS, +2 to 3% for CR, and -3 to 6d of DFS), to such
      a point that F1 crossbreds could compete with Holstein cows for milk production
      while having a better fertility. However, recombination losses suggested that
      some F1 heterosis was lost for backcross cows. 

PMID- 25981070
TI  - Residual feed intake is repeatable for lactating Holstein dairy cows fed high and
      low starch diets.
AB  - Residual feed intake (RFI) is a tool to quantify feed efficiency in livestock and
      is commonly used to assess feed efficiency independent of production level, body
      weight (BW), or BW change. Lactating Holstein cows (n=109; 44 primiparous and 65
      multiparous), averaging (mean +/- standard deviation, SD) 665+/-77kg of BW, 42+/
      9kg of milk/d, and 120+/-30 d postpartum, were fed diets of high (HI) or low (LO)
      starch content in 4 crossover experiments with two 28-d treatment periods. The LO
      diets were ~40% neutral detergent fiber (NDF) and ~14% starch and the HI diets
      were ~26% NDF and ~30% starch. Individual dry matter intake (DMI) of a cow was
      modeled as a function of milk energy output, metabolic BW, body energy change,
      and fixed effects of parity, experiment, cohort nested within experiment, and
      diet nested within cohort and experiment; RFI for each cow was the residual error
      term. Cows were classified as high (>0.5 SD of the mean), medium (+/-0.5 SD of
      the mean), or low (<-0.5 SD of the mean) RFI. On average, for the linear model
      used to determine RFI for individual cows, each unit increase in milk energy
      output, metabolic BW, or body energy gain was associated with 0.35, 0.09, or
      0.05kg increase in DMI, respectively. When compared with LO diets, HI diets
      increased energy partitioning to body energy gain and tended to increase DMI. The
      correlation between RFI when cows were fed HI diets and RFI when cows were fed LO
      diets was 0.73 and was similar across each parity and experiment. Fifty-six
      percent of cows maintained the same RFI classification (high, medium, or low RFI)
      and only 4 of 109 cows changed from high RFI to low RFI or vice versa when diets
      were changed. Milk:feed, income over feed cost, and DMI were also highly
      repeatable (r=0.72, 0.84, and 0.92, respectively). We achieved significant
      changes in milk yield and component concentration as well as energy partitioning
      between HI and LO diets and still determined RFI to be repeatable across diets.
      We conclude that RFI is reasonably repeatable for a wide range of dietary starch
      levels fed to mid-lactation cows, so that cows that have low RFI when fed high
      corn diets will likely also have low RFI when fed diets high in nonforage fiber
      sources. 

PMID- 25981071
TI  - Short communication: Genetic analysis for fertility traits of heifers and cows
      from smallholder dairy farms in a tropical environment.
AB  - The objective of this study was to estimate genetic parameters for various
      fertility traits on Holstein upgraded dairy heifers and cows in a smallholder
      system under tropical conditions using data sets from the Thailand national
      recording scheme. The investigated traits were age at first service (AFS), age at
      first calving (AFC), days from calving to first service (DTFS), days between
      first and last service (DFLS), days open (DO), calving interval (CI), number of
      services per conception (NSPC), and conception at first service (FSC). The data
      consisted of 68,555, 34,401, and 54,004 records on heifers, primiparous, and
      multiparous cows, respectively, calving between 1996 and 2011. Gibbs sampling was
      employed to obtain (co)variance components using both univariate and bivariate
      analyses with linear and threshold animal models. Virgin heifers had better
      fertility performance than primiparous and multiparous cows. The reproductive
      performance in primiparous cows was inferior compared with multiparous cows. Cows
      with higher Holstein-Friesian blood showed lower reproductive efficiency.
      Estimated heritabilities for most of the fertility traits were 0.04 or less
      except for AFS (0.26) and AFC (0.25). The estimated genetic correlations among
      fertility traits within parity indicated that selection for cows with high
      conception rate could lead to shortened DO and CI, as well as DTFS. The FSC and
      NSPC could be used as the best indicators for heifer and cow fertility and could
      be complemented by other traits, which were genetically considered as different
      traits such as DTFS and DFLS in terms of a fertility index. This would enable
      efficient selection for better fertility. Genetic correlations for fertility
      traits in primiparous and multiparous cows were very high (>0.90), but those
      between heifers and cows were lower (0.03 to 0.83). The latter results indicated
      that fertility traits of heifers and cows should be considered as different
      traits. 

PMID- 25981072
TI  - Substitution of common concentrates with by-products modulated ruminal
      fermentation, nutrient degradation, and microbial community composition in vitro.
AB  - A rumen simulation technique was used to evaluate the effects of the complete
      substitution of a common concentrate mixture (CON) with a mixture consisting
      solely of by-products from the food industry (BP) at 2 different forage-to
      concentrate ratios on ruminal fermentation profile, nutrient degradation, and
      abundance of rumen microbiota. The experiment was a 2*2 factorial arrangement
      with 2 concentrate types (CON and BP) and 2 concentrate levels (25 and 50% of
      diet dry matter). The experiment consisted of 2 experimental runs with 12
      fermentation vessels each (n=6 per treatment). Each run lasted for 10d, with data
      collection on the last 5d. The BP diets had lower starch, but higher neutral
      detergent fiber (NDF) and fat contents compared with CON. Degradation of crude
      protein was decreased, but NDF and nonfiber carbohydrate degradation were higher
      for the BP diets. At the 50% concentrate level, organic matter degradation tended
      to be lower for BP and CH4 formation per unit of NDF degraded was also lower for
      BP. The BP mixture led to a higher concentration of propionate and a lower
      acetate-to-propionate ratio, whereas concentrations of butyrate and caproate
      decreased. Concentrate type did not affect microbial community composition,
      except that the abundance of bacteria of the genus Prevotella was higher for BP.
      Increasing the concentrate level resulted in higher degradation of organic matter
      and crude protein. At the higher concentrate level, total short-chain fatty acid
      formation increased and concentrations of isobutyrate and valerate decreased. In
      addition, at the 50% concentrate level, numbers of protozoa increased, whereas
      numbers of methanogens, anaerobic fungi, and fibrolytic bacteria decreased. No
      interaction was noted between the 2 dietary factors on most variables, except
      that at the higher concentrate level the effects of BP on CH4 and CO2 formation
      per unit of NDF degraded, crude protein degradation, and the abundance of
      Prevotella were more prominent. In conclusion, the results of this study suggest
      that BP in the diet can adequately substitute CON with regard to ruminal
      fermentation profile and microbiota, showing even favorable fermentation patterns
      when fed at 50% inclusion rate. 

PMID- 25981073
TI  - Effects of different model diets on milk composition and expression of genes
      related to fatty acid synthesis in the mammary gland of lactating dairy goats.
AB  - This study examined the effects of different roughage diets on milk composition
      and the expression of key genes associated with fatty acid (FA) synthesis in the
      mammary gland of lactating dairy goats. Eight multiparous lactating goats (body
      weight=43.6+/-2.5kg, 90+/-12 d in milk) fitted with external pudic artery and
      subcutaneous abdominal vein catheters were assigned to 2 treatments in a
      crossover design. The goats were fed different roughage diets with a similar
      concentrate-to-roughage ratio. The diets were (1) a high-quality roughage
      treatment (HQR) containing 28.5% Chinese wildrye hay, 19% corn silage, 9.5%
      alfalfa, and 43% concentrate or (2) a low-quality roughage treatment (LQR)
      containing 28% Chinese wildrye hay, 28% corn stover, and 44% concentrate, on a
      dry matter basis. Each feeding period lasted 21 d. The first 18 d served as an
      adaptation period, and the last 3 d served as a sample collection period. Dry
      matter intake, milk yield, and milk composition were measured. Milk and blood
      samples were collected for FA analysis. Mammary gland biopsies were performed
      after milking on the last day of each period and the tissues were analyzed for
      the mRNA expression of acetyl-coenzyme A carboxylase-alpha (ACACA), FA synthase
      (FASN), stearoyl CoA desaturase (SCD), and lipoprotein lipase (LPL). Dry matter
      intake and milk yield were not affected by the treatments. Milk fat (3.16 vs.
      2.96%) and protein (2.99 vs. 2.89%) contents were higher in HQR goats than in LQR
      goats, and milk fat yield tended to be higher in HQR goats (16.7 vs. 15.1g/d).
      Milk FA composition was not different between treatments, except for C18:3n-3
      (0.27 vs. 0.15g/100g). Compared with LQR goats, HQR goats had a higher vein
      concentration of total FA (0.62 vs. 0.44mg/mL). In HQR goats, the mammary balance
      of total FA increased (9.17 vs. 5.51g/d), whereas the clearance rate of total FA
      decreased (103.03 vs. 138.25 L/d). No differences were found in mammary blood
      flow, artery concentration, and mammary uptake of FA between treatments. Compared
      with LQR, the expression of FASN and ACACA tended to be increased by 20 and 18%,
      and the expression of LPL and SCD were increased by 39 and 50% in HQR,
      respectively. The results demonstrated that diets with HQR can increase milk fat
      content and yield as well as the expression of LPL and SCD in the mammary gland
      of dairy goats. 

PMID- 25981074
TI  - Milk prolactin response and quarter milk yield after experimental infection with
      coagulase-negative staphylococci in dairy heifers.
AB  - Coagulase-negative staphylococci (CNS) are the most common bacteria involved in
      subclinical mastitis in dairy cows. Remarkably, CNS-infected dairy heifers
      produce more milk than uninfected heifers. Because the lactation hormone
      prolactin (PRL) is also involved in mammary gland immunity, we investigated the
      milk PRL response and the mammary quarter milk yield following experimental CNS
      challenge. Eight healthy Holstein-Friesian heifers in mid-lactation were
      experimentally infected using a split-udder design with 3 different CNS strains:
      one Staphylococcus fleurettii (from sawdust bedding) and 2 Staphylococcus
      chromogenes strains (one isolate from a teat apex, the other isolate from a
      chronic intramammary infection). Three mammary quarters per heifer were
      simultaneously inoculated with 1.0*10(6) cfu, whereas the remaining mammary
      quarter was infused with sterile phosphate-buffered saline, serving as a control.
      An existing radioimmunoassay was modified, validated, and used to measure PRL
      frozen-thawed milk at various time points until 78h after challenge. The mean
      milk PRL level tended to be higher in the CNS-challenged mammary quarters
      compared with the control mammary quarters (7.56 and 6.85ng/mL, respectively).
      The increase in PRL over time was significantly greater in the CNS-challenged
      mammary quarters than in the control mammary quarters. However, no difference was
      found in the PRL response when comparing each individual CNS strain with the
      control mammary quarters. The mean mammary quarter milk yield tended to be lower
      in the CNS-infected mammary quarters than in the control mammary quarters (1.73
      and 1.98kg per milking, respectively). The greatest milk loss occurred in the
      mammary quarters challenged with the intramammary strain of S. chromogenes.
      Future observational studies are needed to elucidate the relation between PRL,
      the milk yield, and the inflammatory condition, or infection status, of the
      mammary gland. 

PMID- 25981075
TI  - Milk production responses to a change in dietary starch concentration vary by
      production level in dairy cattle.
AB  - The effects of dietary starch concentration on yield of milk and milk components
      were evaluated in a crossover design experiment. Holstein cows (n=32; 115+/-22 d
      in milk) with a wide range in milk yield (28 to 62kg/d) were assigned randomly
      within level of milk yield to a treatment sequence. Treatments were diets
      containing 30% dry ground corn (CG) or 30% soyhulls (SH) on a DM basis. Diets
      containing corn silage and alfalfa silage were formulated to contain 16% crude
      protein, 24% forage neutral detergent fiber, and either 27 or 44% neutral
      detergent fiber and 30 or 12% starch for CG and SH, respectively. Cows were fed a
      diet intermediate to the treatments during a preliminary 14-d period. Treatment
      periods were 28 d with measurements taken throughout the period for energy
      calculations and the final 5 d used for data and sample collection for production
      variables. Compared with SH, CG increased dry matter intake, and yields of milk,
      milk protein, milk fat, and energy-corrected milk, as well as milk protein
      concentration. Treatment did not affect milk fat concentration. Yield of de novo
      synthesized and preformed milk fatty acids increased with CG. Treatment
      interacted with level of preliminary milk production for several response
      variables (yields of milk, milk protein, milk fat, energy-corrected milk, and
      3.5% fat-corrected milk). Compared with SH, the CG treatment increased energy
      corrected milk in higher-producing cows with a lesser response to CG as milk
      yield decreased. The CG treatment increased milk:feed compared with the SH
      treatment, but not body weight or body condition score. In conclusion, higher
      producing cows benefited from the high-starch diet, and lower-producing cows were
      able to maintain production when most of the starch was replaced with nonforage
      fiber. 

PMID- 25981076
TI  - Tomato seeds as a novel by-product feed for lactating dairy cows.
AB  - Whole tomato seeds, a novel by-product feedstuff, were fed to lactating Holstein
      cows to determine the nutritive value of whole tomato seeds by replacing whole
      cottonseed in the total mixed ration. Four primiparous and 4 multiparous Holstein
      cows were used in a 4*4 Latin square design and fed 1 of 4 total mixed rations.
      Whole tomato seeds replaced whole cottonseed on a weight-to-weight basis for
      lipid. The proportion of whole tomato seeds to whole cottonseed in the diets were
      100:0, 50:50, 25:75, and 0:100 on a lipid basis. Thus, tomato seeds were 4.0,
      2.4, 1.1, and 0% of the ration dry matter, respectively. Milk yield and the
      concentrations and yields of protein, lactose, and solids-not-fat did not differ
      for the effect of diet. However, milk fat concentration decreased and milk fat
      yield tended to decrease as whole tomato seeds replaced whole cottonseed. Intakes
      of dry matter, lipid, and crude protein did not differ. Whole-tract apparent
      digestibility of dry matter and ash-free neutral detergent fiber did not differ,
      but digestibility of total fatty acids and crude protein decreased with
      increasing proportion of whole tomato seeds. Urea concentration in milk and
      plasma both decreased with increasing whole tomato seeds. Fecal concentration of
      linoleic and alpha-linolenic acids increased with increasing whole tomato seeds,
      suggesting that seeds were passing out of the digestive tract undigested. The
      concentrations of C18:2n-6 and C18:3n-3 in milk fat had small increases, but
      their yields were not different, suggesting that only a small amount of whole
      tomato-seed lipid might have been digested postruminally. Amounts of trans C18:1
      fatty acids in milk fat were higher with increasing whole cottonseed, which might
      suggest a shift in rumen biohydrogenation pathways. At the level of feeding used
      in the current study, whole tomato seeds replaced whole cottonseed in the diet of
      lactating dairy cows without a change in production. 

PMID- 25981077
TI  - Evaluation of treatments for claw horn lesions in dairy cows in a randomized
      controlled trial.
AB  - Lameness is one of the most significant endemic disease problems facing the dairy
      industry. Claw horn lesions (principally sole hemorrhage, sole ulcer, and white
      line disease) are some of the most prevalent conditions. Despite the fact that
      thousands of animals are treated for these conditions every year, experimental
      evidence is limited on the most effective treatment protocols. A randomized,
      positively controlled clinical trial was conducted to test the recovery of newly
      lame cows with claw horn lesions. Animals on 5 farms were locomotion scored every
      2wk. Cows were eligible for recruitment if they had 2 nonlame scores followed by
      a lame score and had a claw horn lesion on a single claw of a single foot.
      Following a therapeutic trim, enrolled cows were randomly allocated to 1 of 4
      treatments: treatment 1-no further treatment (positive control; TRM), treatment 2
      trim plus a block on the sound claw (TB), treatment 3-trim plus a 3-d course of
      the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (TN), treatment 4-trim
      plus a block plus ketoprofen (TBN). The primary outcome measure was locomotion
      score 35d after treatment, by an observer blind to treatment group. Descriptive
      statistics suggested that treatment groups were balanced at the time of
      enrollment, that is, randomization was successful. Based on a sound locomotion
      score (score 0) 35d after treatment, the number of cures was 11 of 45 (24.4%) for
      TRM, 14 of 39 (35.9%) for TB, 12 of 42 (28.6%) for TN, and 23 of 41 (56.1%) for
      TBN. The difference between TBN and TRM was significant. To test for confounding
      imbalances between treatment groups, logistic regression models were built with 2
      outcomes, either sound (score 0) or nonlame (score 0 or 1) 35d after treatment.
      Compared with TRM, animals that received TBN were significantly more likely to
      cure to a sound outcome. Farm, treatment season, lesion diagnosis, limb affected,
      treatment operator, and stage of lactation were included in the final models. Our
      work suggests that lameness cure is maximized with NSAID treatment in addition to
      the common practices of therapeutic trimming and elevation of the diseased claw
      using a block when cows are newly and predominantly mildly lame. 

PMID- 25981078
TI  - Prevalence of enterotoxin genes and antimicrobial resistance of coagulase
      positive staphylococci recovered from raw cow milk.
AB  - Raw milk may be contaminated by enterotoxigenic coagulase-positive staphylococci
      (CPS). Several of these microorganisms show antimicrobial resistance, which poses
      a potential risk for consumers. The aim of this study was to determine the
      occurrence of enterotoxin genes and antimicrobial resistance of CPS isolated from
      cow milk. A total of 115 samples were analyzed for the presence of CPS according
      to the International Organization for Standardization standard (ISO 6888-2). The
      genes were identified using 2multiplex PCR assays. Resistance of the isolates to
      10 antimicrobials was determined using the minimum inhibitory concentration
      method. Overall, 71 samples (62%) were contaminated with CPS and 69 isolates were
      further analyzed. Among them, 20 (29%) strains harbored the enterotoxin genes.
      The most commonly detected staphylococcal enterotoxin markers were sed, sej, and
      ser, whereas none of the analyzed isolates possessed the seb and see genes.
      Almost one-half of the tested strains (43%) were resistant to one or more
      antimicrobial agents. Resistance to penicillin was the most common, followed by
      sulfamethoxazole and chloramphenicol. On the other hand, all strains were
      susceptible to ciprofloxacin, erythromycin, gentamicin, cefoxitin, and
      streptomycin. None of the strains was positive for the mecA and mecC (methicillin
      resistant Staphylococcus aureus) genes. These results indicate that
      enterotoxigenic and antimicrobial-resistant CPS strains are present in raw milk,
      which may be a potential risk for public health. 

PMID- 25981079
TI  - Modeling the trade-off between diet costs and methane emissions: A goal
      programming approach.
AB  - Enteric methane emission is a major greenhouse gas from livestock production
      systems worldwide. Dietary manipulation may be an effective emission-reduction
      tool; however, the associated costs may preclude its use as a mitigation
      strategy. Several studies have identified dietary manipulation strategies for the
      mitigation of emissions, but studies examining the costs of reducing methane by
      manipulating diets are scarce. Furthermore, the trade-off between increase in
      dietary costs and reduction in methane emissions has only been determined for a
      limited number of production scenarios. The objective of this study was to
      develop an optimization framework for the joint minimization of dietary costs and
      methane emissions based on the identification of a set of feasible solutions for
      various levels of trade-off between emissions and costs. Such a set of solutions
      was created by the specification of a systematic grid of goal programming
      weights, enabling the decision maker to choose the solution that achieves the
      desired trade-off level. Moreover, the model enables the calculation of emission
      mitigation costs imputing a trading value for methane emissions. Emission imputed
      costs can be used in emission-unit trading schemes, such as cap-and-trade policy
      designs. An application of the model using data from lactating cows from dairies
      in the California Central Valley is presented to illustrate the use of model
      generated results in the identification of optimal diets when reducing emissions.
      The optimization framework is flexible and can be adapted to jointly minimize
      diet costs and other potential environmental impacts (e.g., nitrogen excretion).
      It is also flexible so that dietary costs, feed nutrient composition, and animal
      nutrient requirements can be altered to accommodate various production systems. 

PMID- 25981080
TI  - Partitioning variation in nutrient composition data of common feeds and mixed
      diets on commercial dairy farms.
AB  - A large project involving commercial dairy farms was undertaken to identify
      important sources of variation in composition data of common feeds and mixed
      diets. This information is needed to develop appropriate sampling schedules for
      feeds and should reduce the uncertainty associated with the nutrient composition
      of delivered diets. The first subproject quantified sources of variation in the
      composition of corn and haycrop silages over a 2-wk period. Silages from 11
      commercial dairy farms in Ohio and Vermont were sampled daily over a 14-d period.
      Most silages were sampled in duplicate each day, and all samples were assayed in
      duplicate. Total variance was partitioned into analytical, sampling, farm, and
      true day-to-day components. Farm was the largest source of variation, but within
      farm variance was our primary interest. Sampling variance comprised 30 to 81% of
      within-farm variance depending on nutrient and type of silage. For dry matter,
      true day-to-day variation was the greatest source of variance, but for most other
      nutrients, sampling was the largest source of within-farm variation. The second
      subproject consisted of sampling feeds and total mixed rations (TMR) from 47
      commercial dairy farms across the United States. Feeds and TMR were sampled
      monthly. Because samples were not assayed in duplicate, source of variation
      included farm, month, and residual (sampling plus analytical). For corn and
      alfalfa silages, month-to-month variation over a 12-mo period comprised about
      twice as much of the total within-farm variation as did day-to-day variation over
      a 14-d period in the first subproject. Although month-to-month variation was
      greater than sampling variation, sampling still accounted for 9 to 37% of the
      total within-farm variance for those 2 feeds. For TMR, sampling plus analytical
      variance accounted for approximately 40 to 70% of the total within-farm variance
      (depending on the nutrient). Variance components were estimated for several
      nutrients and for several common feeds. The contributions to total variance
      differed depending on feed and nutrient, but the information provided will help
      in determining whether on-farm samples should be taken and if so, how often. A
      major implication of this project is that sampling is a substantial source of
      variation in silages, concentrates, and TMR, and data from a single sample are
      likely not highly reliable. 

PMID- 25981081
TI  - Prediction of different ovarian responses using anti-Mullerian hormone following
      a long agonist treatment protocol for IVF.
AB  - OBJECTIVE: The purpose of this study was to predict the poor and excessive
      ovarian response using anti-Mullerian hormone (AMH) levels following a long
      agonist protocol in IVF candidates. RESEARCH DESIGN AND METHODS: Through a
      prospective cohort study, the type of relationship and appropriate scale for AMH
      were determined using the fractional polynomial regression. To determine the
      effect of AMH on the outcomes of ovarian stimulation and different ovarian
      responses, the multi-nominal and negative binomial regression models were fitted
      using backward stepwise method. The ovarian response of study subject who entered
      a standard long-term treatment cycle with GnRH agonist was evaluated using
      prediction model, separately and in combined models with (ROC) curves. RESULTS:
      The use of standard long-term treatments with GnRH agonist led to positive
      pregnancy test results in 30% of treated patients. With each unit increase in the
      log of AMH, the odds ratio of having poor response compared to normal response
      decreases by 64% (OR 0.36, 95% CI 0.19-0.68). Also the results of negative
      binomial regression model indicated that for one unit increase in the log of AMH
      blood levels, the odds of releasing an oocyte increased 24% (OR 1.24, 95% CI 1.14
      1.35). The optimal cut-off points of AMH for predicting excessive and poor
      ovarian responses were 3.4 and 1.2 ng/ml, respectively, with area under curves of
      0.69 (0.60-0.77) and 0.76 (0.66-0.86), respectively. CONCLUSION: By considering
      the age of the patient undergoing infertility treatment as a variable affecting
      ovulation, use of AMH levels showed to be a good test to discriminate between
      different ovarian responses.

PMID- 25981084
TI  - Transforming and advancing health equity: Dr. Howard Kyongju Koh.

PMID- 25981083
TI  - Prediction of wound healing after minor amputations of the diabetic foot.
AB  - AIM: To identify any significant differences in physiological test results
      between healing and non healing amputation sites. METHODS: A single center
      prospective non-experimental study design was conducted on fifty subjects living
      with type 2 diabetes and requiring a forefoot or toe amputation. Subjects
      underwent non-invasive physiological testing preoperatively. These included
      assessment of pedal pulses, preoperative arterial spectral waveforms at the
      ankle, absolute toe pressures, toe-brachial pressure index and ankle-brachial
      pressure index. After 6 weeks, patients were examined to assess whether the
      amputation site was completely healed, was healing, had developed complications,
      or did not heal. RESULTS: There was no significant difference in ABPI between the
      healed/healing and the non-healing groups. Mean TBI (p=0.031) and toe pressure
      readings (p=0.014) were significantly higher in the healed/healing group compared
      to the non healing group. A significant difference was also found in ankle
      spectral waveforms between the two groups (p=0.028). CONCLUSIONS: TBIs, toe
      pressures and spectral waveforms at the ankle are better predictors of likelihood
      of healing and non-healing after minor amputation than ABPIs. ABPI alone is a
      poor indicator of the likelihood of healing of minor amputations and should not
      be relied on to determine need for revascularization procedures before minor
      amputation.

PMID- 25981082
TI  - Assessment of human lymphocyte proliferation associated with metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS), a cluster of various metabolic conditions,
      has become epidemic and causes increased morbidity and mortality. PURPOSE: The
      aim of this study was to compare lymphocyte proliferation under two different
      stimuli, Concanavalin A (ConA) and insulin, in a group of patients with MetS
      (Group 1) and a healthy group (Group 2). METHODS: Group 1 consisted of 53
      patients who met the diagnostic criteria for MetS. Group 2 consisted of 63
      patients without MetS. All individuals were evaluated for lipid profile and
      glycemia. Lymphocyte extraction and culture were performed for each subject and
      lymphocyte proliferation was assessed using the Alamar blue technique. RESULTS:
      There was no gender difference between both groups, but in terms of age, there
      was a significant difference. The use of Con A at concentrations of 1 and 5 ug/mL
      induced a high lymphocyte proliferation in both groups. In contrast, when
      different concentrations of insulin were added, no significant changes in
      lymphocyte proliferation were observed. However, the proliferation of lymphocytes
      was significantly higher in Group 1 compared to Group 2 under insulin stimulus,
      which did not happen under ConA stimulation. Even after age and gender
      correction, this difference was maintained. CONCLUSIONS: The increased lymphocyte
      proliferative response to insulin in patients with MetS found in this study
      suggests a role of the lymphocyte response to insulin in the pathophysiology of
      MetS. This response may be used as an immuno-biological marker for MetS, although
      further studies to evaluate its clinical usefulness need to be conducted.

PMID- 25981085
TI  - Championing partnerships for data equity.

PMID- 25981086
TI  - Type 2 Diabetes among 6 Asian Ethnic Groups in California: The Nexus of
      Ethnicity, Gender, and Generational Status.
AB  - OBJECTIVES: We examined associations between generational status and age-adjusted
      type 2 diabetes (T2DM) among Asians living in California. METHODS: We abstracted
      data on 7,188 Asian Americans of six ethnicities from the 2007 and 2009
      California Health Interview Survey. Age-and ethnicity-specific logistic
      regression analyses were used to model prevalence of T2DM based on 29
      generational status and language spoken at home. RESULTS: Second-generation Asian
      men and first-generation Asian women had higher T2DM prevalence compared with
      their White peers. Such a trend was observed among Chinese and Filipino men, and
      Filipina and Korean women. In addition, Filipinas who spoke only English at home
      had lower odds of T2DM than other Filipinas (OR=0.3, 95% CI: 0.1-1.0) while the
      relationship was reversed among Filipino men (OR=3.2, 95% CI 1.0-10.1).
      CONCLUSIONS: Associations between generational status and T2DM among Asian
      Americans are non-linear and strongly influenced by gender and ethnicity.

PMID- 25981087
TI  - Increasing cervical cancer screening among Vietnamese Americans: a community
      based intervention trial.
AB  - Vietnamese women experience a significant health disparity in incidence and
      mortality rates and screening of cervical cancer. This study is to evaluate the
      effectiveness of a multifaceted and culturally appropriate intervention in
      increasing Pap testing rates to reduce cervical cancer disparity in this high
      risk population. METHODS: A total of 30 Vietnamese community organizations were
      randomized to either intervention or control condition. Participants (n=1,416)
      completed 12-month follow-up of Pap testing, their self-reported and medical
      record data were collected and analyzed. RESULTS: The findings showed a
      statistically significant increase in Pap testing among intervention group than
      control group (significance p<.0001). The self-reported Pap test screening rate
      is in high agreement with that of validated medical records. CONCLUSION: Results
      indicate the screening rate was significantly higher in Vietnamese women in the
      intervention group compared with the control. Despite large intervention effect,
      there still remains a gap to reach Healthy People 2020 goal of 93% screening
      rate.

PMID- 25981088
TI  - Overweight and Obesity Prevalence among Public School Children in Guam.
AB  - BACKGROUND: The Government of Guam passed Public Law 28-87, which established the
      collection of child Body Mass Index (BMI) measurements in the Guam Department of
      Education (GDOE). This paper aimed to analyze the BMI data and report the
      childhood obesity prevalence on Guam. METHODS: Secondary analysis was performed
      on a repeated cross-section of 106,827 children in the GDOE from 2010 to 2014.
      Age- and sex-specific prevalence estimates and 95% Confidence Intervals (CI) by
      weight status were calculated for each year. Test for trends in the high weight
      status were performed. RESULTS: The childhood obesity prevalence was 23.1% (95%
      CI, 22.9%-23.4%). It declined from 23.6% (95% CI, 23.1%-24.1%) in 2010-2011 to
      22.6% (95% CI, 22.1%-23.0%) in 2013-2014 (p=.007). CONCLUSION: Childhood obesity
      on Guam has declined, though it remains higher than the U.S. Mainland. Continued
      BMI data collection is needed to monitor childhood obesity and measure the impact
      of Public Law 28-87.

PMID- 25981089
TI  - Cost Burden of Potentially Preventable Hospitalizations for Cardiovascular
      Disease and Diabetes for Asian Americans, Pacific Islanders, and Whites in
      Hawai'i.
AB  - We compared the cost burdens of potentially preventable hospitalizations for
      cardiovascular disease and diabetes for Asian Americans, Pacific Islanders, and
      Whites using Hawai'i statewide 2007-2012 inpatient data. The cost burden of the
      27,894 preventable hospitalizations over six years (total cost: over $353
      million) fell heavily on Native Hawaiians who had the largest proportion (23%) of
      all preventable hospitalizations and the highest unadjusted average costs
      (median: $9,117) for these hospitalizations. Diabetes-related amputations (median
      cost: $20,167) were the most expensive of the seven preventable hospitalization
      types. After adjusting for other factors (including age, insurance, and
      hospital), costs for preventable diabetes-related amputations were significantly
      higher for Native Hawaiians (ratio estimate:1.23; 95%CI:1.05-1.44), Japanese
      (ratio estimate:1.44; 95%CI:1.20-1.72), and other Pacific Islanders (ratio
      estimate:1.26; 95%CI:1.04-1.52) compared with Whites. Reducing potentially
      preventable hospitalizations would not only improve health equity, but could also
      relieve a large and disproportionate cost burden on some Pacific Islander and
      Asian American communities. 

PMID- 25981090
TI  - Children's Healthy Living Program (CHL) Indigenous Workforce Training to Prevent
      Childhood Obesity in the Underserved U.S. Affiliated Pacific Region.
AB  - The U.S. Affiliated Pacific Region (USAPR) is an underserved region with high
      rates of obesity-related, non-communicable diseases and a low proportion of
      trained obesity prevention professionals, especially indigenous professionals.
      The Children's Healthy Living Training Program was developed to enhance the
      USAPR's capacity to address childhood obesity prevention. 

PMID- 25981091
TI  - Policy, System, and Environment Strategies to Promote Physical Activity and
      Healthy Food Sources to Address Guam's Disparate Non-Communicable Disease Burden.
AB  - In 2013, the Guam Non-Communicable Disease (NCD) Consortium, Department of Public
      Health and Social Services, and University of Hawaii collaborated to address
      Guam's NCD burden. This field report describes their efforts to implement policy,
      system, and environmental interventions through the worksite wellness and
      community garden programs. 

PMID- 25981092
TI  - Identifying and understanding the role of key stakeholders in promoting worker
      health and safety in nail salons.
AB  - The nail salon sector is booming, predominantly with Vietnamese immigrant workers
      who regularly handle nail care products containing harmful chemicals. Based on
      lessons learned from an ongoing randomized controlled trial, occupational
      interventions need to incorporate inputs from different stakeholders, including
      salon owners, workers, and customers as well as governmental regulatory agencies.

PMID- 25981094
TI  - Litigation and Community Advocacy to Ensure Health Access for Micronesian
      Migrants in Hawai'i.
AB  - The Federated States of Micronesia and the Republics of Palau and the Marshall
      Islands signed a series of treaties known as the Compacts of Free Association
      (COFA) with the United States (U.S.). While the islands became independent
      nations, certain rights and responsibilities were assigned to the U.S. However
      since the signing of the treaties, U.S. federal and Hawai'i state policies have
      reduced health care coverage for COFA migrants living in the U.S. and its
      territories. This commentary reports the ongoing efforts of the Micronesian
      community and its allies to rectify a legacy of unjust policies. We outline the
      need for sound policies that support appropriate health care to all members of
      society, and highlight the community's strength and ability to mobilize for
      political action. If health is a human right, providing adequate, equitable
      health care to all members of society is not up for debate. 

PMID- 25981093
TI  - Improving Access to Healthy Foods for Asian Americans, Native Hawaiians, and
      Pacific Islanders: Lessons Learned from the STRIVE Program.
AB  - Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs) experience a
      large burden from certain chronic disease-related risk factors. The STRIVE
      Program funded four AANHPI community-based organizations (CBOs) to implement
      culturally adapted community gardens and farmers' markets to increase access to
      healthy foods. Key CBO informant interviews were conducted to understand
      processes and lessons learned. 

PMID- 25981096
TI  - Community collaborative for colorectal cancer screening in Los Angeles Koreatown.
AB  - Colorectal cancer (CRC) rates are high among Korean Americans due in large part
      to low rates of screening. The Asian American Network for Cancer Awareness,
      Research, and Training (AANCART) developed the Korean CRC Project to increase
      awareness of and access to CRC screening for Los Angeles County Korean Americans.

PMID- 25981097
TI  - Risk Factors for Childhood Obesity among Asian Americans: A Systematic Review of
      Literature and Recommendations for Health Care Research.
AB  - Childhood obesity has become an epidemic across all racial/ethnic groups in the
      U.S., including Asian Americans. With different cultures, beliefs, and
      lifestyles, Asian Americans may face unique sets of risk factors for childhood
      obesity. This review critically assesses and summarizes the literature on risk
      factors for childhood obesity among Asian Americans. Among the 14 studies
      identified, five (35.7%) used national or state-level data, seven (50%) targeted
      Chinese Americans, and two (14.3%) focused on Hmong Americans. Multiple risk
      factors for childhood obesity among Asian Americans were reported, including
      acculturation, generational status, and family functioning. Limitations of the
      literature included use of small samples, scarcity of ethnically specific data
      for Asian American subgroups, shortage of qualitative studies, and lack of
      theoretical foundation. More disaggregated studies are needed to examine the
      important variability that may exist in risk factors for childhood obesity among
      Asian American subgroups. 

PMID- 25981095
TI  - Defining an integrative approach for health promotion and disease prevention: a
      population health equity framework.
AB  - Eliminating health disparities in racial/ethnic minority and underserved
      populations requires a paradigm shift from biomedical approaches that are disease
      focused to a health equity framework that aims to achieve optimal health for all
      by targeting social and structural determinants of health. We describe the
      concepts and parallel approaches that underpin an integrative population health
      equity framework and present the experience of NYU Center for the Study of Asian
      American Health (CSAAH) in applying the framework to guide its work. Applying an
      integrative framework has deepened our community engagement efforts, our
      understanding of the multi-level contextual factors that influence health, and
      our capacity to advance health equity for Asian American communities through
      action-oriented research and policy. This framework and experience is applicable
      to researchers and community members working with other underserved populations. 

PMID- 25981098
TI  - Risk Factors of Suicide and Depression among Asian American, Native Hawaiian, and
      Pacific Islander Youth: A Systematic Literature Review.
AB  - Suicide has become an increasing public health challenge, with growing incidence
      among Asian American, Native Hawaiian, and Pacific Islander (AA and NHPI) youth.
      Using an ecological framework, the purpose of this systematic review was to
      explicate risk and protective factors for depression or suicide among AA and NHPI
      youth from available peer reviewed research. The ecological framework provides a
      useful blueprint for translating social determinants of health to explain the
      experience of depression and suicidal behaviors among AA and NHPI youth. Sixty
      six studies were extracted from PsychInfo, Ovid Med-line, EMBASE, CINAHL, and Web
      of Science. Policy and practice recommendations are offered in light of relevant
      themes that emerged. Further research and data disaggregation is needed to
      develop and strengthen population health strategies, interventions, and policies
      that address the underlying social conditions and cultural contexts of mental
      health disparities associated with depression and suicide among AA and NHPI
      youth. 

PMID- 25981099
TI  - Characteristics of Asian American, Native Hawaiian, and Pacific Islander
      community health worker programs: a systematic review.
AB  - Community health workers (CHWs) are frontline health workers who often serve
      socially and linguistically isolated populations, including Asian American,
      Native Hawaiian, and Pacific Islander (AA and NHPI) communities in the United
      States (U.S.) and U.S. territories. We conducted a systematic review of the peer
      reviewed literature to assess the characteristics of CHW programs for AA and NHPI
      communities in the U.S. and U.S. territories, generating a total of 75 articles.
      Articles were coded using eight domains: ethnic group, health topic, geographic
      location, funding mechanism, type of analysis reported, prevention/management
      focus, CHW role, and CHW title. Articles describing results of an intervention or
      program evaluation, or cost-effectiveness analysis were further coded with seven
      domains: study design, intervention recruitment and delivery site, mode of
      intervention delivery, outcomes assessed, key findings, and positive impact.
      Results revealed gaps in the current literature and point towards recommendations
      for future CHW research, program, and policy efforts. 

PMID- 25981100
TI  - Introduction: shining the light on Asian American, Native Hawaiian, and Pacific
      Islander health.

PMID- 25981101
TI  - A novel non-invasive ultrasonic method to assess total axial stress of the common
      carotid artery wall in healthy and atherosclerotic men.
AB  - In the present study, developing a new non-invasive method independent from blood
      flow, we estimated and compared the total axial stress of the common carotid
      artery wall in healthy and atherosclerotic subjects. Consecutive ultrasonic
      images of the common carotid artery of 48 male subjects including healthy, with
      less and more than 50% stenosis in carotid artery were recorded. Longitudinal
      displacement and acceleration was extracted from ultrasonic image processing
      using a block matching algorithm. Furthermore, images were examined using a
      maximum gradient algorithm and time rate changes of the internal diameter and
      intima-media thickness were extracted. Finally, axial stress was estimated using
      an appropriate constitutive equation. Statistical analysis results showed that
      with stenosis initiation and its progression, axial acceleration and stress
      increase significantly. According to the results of the present study, maximum
      axial stress of the arterial wall is 1.713+/-0.546, 1.993+/-0.731 and 2.610+/
      0.603 (kPa) in normal, with less and more than 50% stenosis in carotid artery
      respectively. Whereas minimum axial stress is -1.714+/-0.676, -1.982+/-0.663 and 
      2.593+/-0.661 (kPa) in normal, with less and more than 50% stenosis in carotid
      artery respectively. Moreover, internal diameter and intima-media thickness of
      the artery also increase significantly with stenosis initiation and its
      progression. In this study, the feasibility of axial wall stress computation for
      human common carotid arteries based on non-invasive in vivo clinical data is
      concluded. We found a strong and graded association between axial stress and
      severity of carotid stenosis, which might be used to discriminate healthy from
      atherosclerotic arteries. 

PMID- 25981102
TI  - What is the best candidate allograft for ACL reconstruction? An in vitro
      mechanical and histologic study in a canine model.
AB  - The knee joint is generally characterized by very low friction and high wear
      resistance. Several previous studies have compared ACL with the commonly used
      allografts from tensile properties perspective. No study has reported about the
      graft tendons from a frictional perspective, which is an important parameter for
      ACL functional performance. Twenty hind legs were used to harvest FDP tendon,
      ACL, ACH, and patellar tendon. Samples were evaluated with surface friction
      testing, indentation testing for tendon compressive moduli, lubricin
      immunohistochemistry, and histologic analysis. Frictional force of FDP tendon and
      ACL was significantly less than that of patellar tendon and ACH at first and
      fifth cycles. At the tenth cycle, the FDP tendon, ACL, and ACH showed
      significantly less frictional force than patellar tendon; after 100 cycles, the
      FDP tendon and ACL showed significantly less frictional force than patellar
      tendon. The compressive moduli of the FDP tendon, ACL, and ACH were significantly
      greater than that of patellar tendon. Histologic results showed that FDP tendon
      and ACL had a smooth surface with a thin layer of epitenon cells; patellar tendon
      and ACH had a rough surface and a layer of paratenon. Lubricin was found on the
      surface and extracellular matrix of FDP tendon and ACL. There was only limited
      lubricin expression on the surface and extracellular matrix of the ACH and
      patellar tendon. The FDP tendon has friction force and lubricin expression
      similar to those of native ACL. However, patellar tendon and ACH show higher
      friction force and less lubricin expression than ACL. 

PMID- 25981103
TI  - The prevalence of intestinal trichomonads in Chinese pigs.
AB  - Intestinal infection of pigs with trichomonads, (Tritrichomonas suis,
      Tetratrichomonas buttreyi, and Pentatrichomonas hominis) has been reported in
      many countries, such as the Philippines, Belgium, and the Czech Republic.
      However, the prevalence of trichomonads infection of swine in China has not yet
      been investigated. In this study, we used small subunit ribosomal RNA genes to
      detect the prevalence of T. suis, T. buttreyi and P. hominis among 158 fecal
      specimens from healthy pigs. Infection rates were 12.03%(19/158), 14.57%
      (23/158), and 24.05% (38/158) for T. suis, T. buttreyi and P. hominis,
      respectively. Molecular evolutionary analysis showed minor allelic variation in
      T. buttreyi from China compared to T. buttreyi isolated from other hosts in
      different parts of the world. 

PMID- 25981104
TI  - Experimental platynosomosis: Characterization of parasite development in the
      mouse model.
AB  - Despite the veterinary importance of species of Platynosomum, biliary trematode
      parasites of birds and mammals with worldwide distribution and a growing role in
      feline practice, the basic parasitological aspects of platynosomosis is still not
      completely understood due to the scarcity of studies in experimental models. In
      the present study, metacercariae of Platynosomum illiciens obtained from
      naturally infected tropical house geckos (Hemidactylus mabouia) in an urban area
      of Brazil were force-fed to mice of the AKR/J strain (100 metacercariae/animal).
      Groups of mice were euthanized at 60, 120, 160 and 240 days post-infection (DPI),
      and the biliary tree of the animals (intrahepatic biliary ducts, common hepatic
      and bile ducts, cystic duct and gallbladder) were examined for the presence of
      adult parasites. Recovered flukes were counted, classified by their site of
      origin (i.e., intrahepatic or extrahepatic biliary ducts) and morphologically
      analyzed under light microscope. The number of adult parasites obtained at 60,
      120, 160 and 240 DPI was 22 +/- 6 (16-32), 41 +/- 14 (18-48), 27 +/- 11 (18-40)
      and 20 +/- 6 (13-30), respectively, and no significant differences in total worm
      burden at the different experimental times were observed. However, 41%, 51%, 75%
      and 95% of the parasites were found in the common hepatic and bile ducts at 60,
      120, 160 and 240 DPI, respectively, suggesting the occurrence of parasitic
      migration to the extrahepatic biliary tree during infection; however, no
      parasites were observed in the gallbladder or cystic duct. Regarding the
      morphometric analysis, progressive growth of P. illiciens during the experimental
      time was observed, and the parasites collected from the extrahepatic bile ducts
      were larger than those obtained from the intrahepatic ducts at the same time of
      infection. Parasites obtained from the extrahepatic biliary tree of the mice at
      160 DPI had similar measurements to those of parasites obtained at 240 DPI, and
      those measurements were equivalent to those reported for parasites from natural
      hosts (cats, birds and nonhuman primates). The results obtained provide new
      insights into the biology of P. illiciens, and the kinetics of the parasite
      development of this species is presented here for the first time. The potential
      use of mice as an experimental model for P. illiciens is presented and the
      implications of the results obtained in that model for feline platynosomosis are
      briefly discussed.

PMID- 25981105
TI  - The first identification of a blood-sucking abomasal nematode Ashworthius sidemi
      in cattle (Bos taurus) using simple polymerase chain reaction (PCR).
AB  - A simple polymerase chain reaction (PCR) test was used to identify Ashworthius
      sidemi, a blood-sucking gastrointestinal nematode that commonly infects bison,
      red and roe deer, and moose in Poland. The present study uses this technique to
      confirm the possibility of transmission of A. sidemi infection from wildlife to
      domestic animals, such as cattle and sheep, grazing on the same natural pastures.
      A 406 bp fragment of genomic A. sidemi DNA was actually detected in DNA isolated
      from larval cultures derived from feces from cattle. A. sidemi DNA has been
      detected in cattle which represent a new host for this parasite. This is the
      first evidence of A. sidemi in cattle. The results reveal that a PCR test based
      on DNA from L3 larvae can be used for in vivo detection of A. sidemi invasions in
      breeding animals. In conclusion, the transfer of A. sidemi infection from
      wildlife to the farm animals sharing the same pastures appears possible.

PMID- 25981106
TI  - Ferritin M of Paralichthys olivaceus possesses antimicrobial and antioxidative
      properties.
AB  - Ferritin is an evolutionarily conserved protein that plays a vital role in
      maintaining iron homeostasis. In this study, we identified a ferritin M (PoFerM)
      from Japanese flounder (Paralichthys olivaceus) and analyzed its biological
      property. PoFerM is composed of 176 amino acid residues and contains the
      conserved ferroxidase diiron center and the ferrihydrite nucleation center
      typical of M ferritins. Expression of PoFerM occurred in multiple tissues and was
      most abundant in blood. Bacterial infection upregulated PoFerM expression in head
      kidney, spleen, and liver in a time-dependent manner. Recombinant PoFerM
      (rPoFerM) purified from Escherichia coli exhibited iron-chelating activity and
      inhibited bacterial growth, whereas rPoFerMM, the mutant protein that bears
      alanine substitution at two conserved residues of the ferroxidase center and the
      ferrihydrite nucleation center, failed to do so. Oxidative protection analysis
      showed that rPoFerM, but not rPoFerMM, was able to alleviate the deleterious
      effect of H2O2-induced free radicals on plasmid DNA and primary flounder cells.
      Together these results indicate that PoFerM is an iron chelator with
      antimicrobial and antioxidative properties, all which depend on the conserved
      ferroxidase center and the ferrihydrite nucleation site. 

PMID- 25981107
TI  - One-pot laser-assisted synthesis of porous carbon with embedded magnetic cobalt
      nanoparticles.
AB  - A novel one-pot laser-assisted approach is reported herein for the synthesis of
      ordered carbons with embedded cobalt nanoparticles. The process is based on a UV
      pulsed laser exposure of an ethanolic solution consisting of green carbon
      precursors, a structure directing agent and a cobalt salt. Very short irradiation
      times (5 to 30 min) are only required to polymerize and cross-link carbon
      precursors (i.e. phloroglucinol and glyoxylic acid) independent of a catalyst
      presence. The influence of three metallic salts (acetate, nitrate and chloride)
      on the phenolic resin and carbon characteristics (structure, texture and particle
      size/distribution) was systematically studied. When exposed to UV laser, the
      metallic salt exhibited a strong influence on the particle size and distribution
      in the carbon matrix rather than on the textural carbon properties. Using cobalt
      acetate, very small (3.5 nm) and uniformly dispersed particles were obtained by
      this simple, fast and green one-pot synthesis approach. An original combined
      (13)C CP-MAS and DP-DEC solid state NMR spectroscopy analysis allowed to
      determine the structure of phenolic resins as well as the location of the cobalt
      salt in the resin. Complementarily, the (1)H solid-state and relaxation NMR
      provided unique insights into the rigidity (cross-linking) of the phenolic resin
      and dispersion of the cobalt salt. The magnetic properties of cobalt
      nanoparticles were found to be size-dependent: large Co nanoparticles (~50 nm)
      behave as bulk Co whereas small Co nanoparticles are superparamagnetic. 

PMID- 25981108
TI  - Promotion of EGF receptor signaling improves the quality of low developmental
      competence oocytes.
AB  - Oocytes acquire developmental competence with progressive folliculogenesis.
      Cumulus oocyte complexes (COCs) from small antral follicles have inherent low
      competence and are poorly responsive to amphiregulin (AREG) which normally
      mediates oocyte maturation and ovulation. Using low competence porcine COCs, in
      an in vitro AREG-induced oocyte maturation system, the combined exposure to
      N(6),2'-O-dibutyryladenosine 3':5' cyclic monophosphate (cAMP) and bone
      morphogenetic protein 15 (B15) and growth differentiation factor 9 (G9) was
      necessary to enhance the rate of oocyte meiotic maturation and blastocyst
      formation. Furthermore, the combination of cAMP+B15+G9 enabled AREG-stimulated
      cumulus expansion and increased expression of the matrix-related genes HAS2,
      TNFIPA6 and PTGS2. Additionally, the combination enhanced p-ERK1/2 which is
      downstream of the EGF receptor. The enhanced nuclear maturation and blastocyst
      formation rates with the combinational treatment were ablated by an EGF receptor
      phosphorylation inhibitor. These results indicate that cAMP and oocyte-secreted
      factors cooperate to promote EGF receptor functionality in developing COCs,
      representing a key component of the acquisition of oocyte developmental
      competence. 

PMID- 25981109
TI  - Is there a limit to transanal endoscopic surgery? A comparative study between
      standard and technically challenging indications among 168 consecutive patients.
AB  - AIM: To assess the surgical outcome of transanal endoscopic surgery (TES) for
      rectal neoplasms in technically challenging indications. METHOD: All patients who
      underwent TES for a rectal neoplasm from 2007 to 2014 were included. Technically
      challenging indications included a tumour with (i) diameter >= 5 cm, (ii)
      involving >= 50% of the rectal circumference and (iii) located >= 10 cm from the
      anal verge. Patients were divided into three groups according to how many of
      these features they had, as follows: Group 1, none; Group 2, one; Group 3, two or
      more. RESULTS: Of the 168 patients (80 benign and 88 malignant tumours) included
      in the study, 73 (44%) were in Group 1, 46 (27%) in Group 2 and 49 (29%) in Group
      3. There was no difference between Group 1 and Group 2 with regard to peritoneal
      perforation (P = 0.210), severe postoperative morbidity (P = 0.804), length of
      hospital stay (P = 0.444), incomplete resection (P = 0.441), piecemeal resection
      (P = 0.740), locoregional recurrence (P = 0.307) and long-term symptomatic rectal
      stenosis (P = 0.076). Conversely Group 3 showed significantly impaired results
      compared with Group 1 with regard to peritoneal perforation (P = 0.003),
      piecemeal resection (P = 0.005), incomplete resection (P = 0.025), locoregional
      recurrence (P = 0.035) and long-term symptomatic rectal stenosis (P < 0.001), but
      no difference in severe postoperative morbidity (P = 0.328). CONCLUSION:
      Transanal endoscopic surgery for rectal neoplasms appears to be safe and
      effective, even in patients presenting with a technically challenging tumours.
      Although the short- and long-term outcomes after TES are worse in patients with
      highly challenging tumours, nevertheless the technique should still be considered
      in patients at high risk of requiring a proctectomy.

PMID- 25981110
TI  - Platycodin D attenuates acute lung injury by suppressing apoptosis and
      inflammation in vivo and in vitro.
AB  - Platycodin D (PLD) is the major triterpene saponin in the root of Platycodon
      grandiflorum (Jacq.) with various pharmacological activities. The purpose of the
      present study was to evaluate the protective effects and possible mechanisms of
      PLD on acute lung injury (ALI) both in vivo and in vitro. In vivo, we used two
      ALI models, lipopolysaccharide (LPS)-induced ALI and bleomycin (BLE)-induced ALI
      to evaluate the protective effects and possible mechanisms of PLD. Female BALB/c
      mice were randomly divided into the following groups: control group, LPS group,
      LPS plus pre-treatment with dexamethasone (2 mg/kg) group, LPS plus pre-treatment
      with PLD groups (50 mg/kg, 100 mg/kg), LPS plus post-treatment with dexamethasone
      (2 mg/kg) group, LPS plus post-treatment with PLD groups (50 mg/kg, 100 mg/kg),
      BLE group, BLE plus pre-treatment with dexamethasone (2 mg/kg) group, BLE plus
      pre-treatment with PLD groups (50 mg/kg, 100 mg/kg), BLE plus post-treatment with
      dexamethasone (2 mg/kg) group, and BLE plus post-treatment with PLD groups (50
      mg/kg, 100 mg/kg). PLD was orally administered before or after LPS or BLE
      challenge with mice. Mice were sacrificed, and lung tissues and bronchoalveolar
      fluid (BALF) were prepared for further analysis. Our results showed that PLD
      significantly decreased lung wet-to-dry weight ratio (lung W/D weight ratio),
      total leukocyte number and neutrophil percentage in the BALF, and myeloperoxidase
      (MPO) activity of lung in a dose-dependent manner. Besides, cytokine levels,
      including interleukin (IL)-6, tumor neurosis factor (TNF)-alpha were also found
      significantly inhibited in BALF. Furthermore, PLD effectively inhibited the
      expressions of nuclear factor kappaB (NF-kappaB), Caspase-3 and Bax in the lung
      tissues, as well as restored the expression of Bcl-2 in the lungs and improved
      the superoxide dismutase (SOD) activity in BALF. In vitro, we used LPS-challenged
      cell model to evaluate the protective effects and possible mechanisms of PLD. MLE
      12 cells were stimulated with LPS in the presence and absence of PLD. The levels
      of TNF-alpha, IL-6 and the expressions of NF-kappaB, Caspase-3, and Bax were
      remarkably down-regulated, while the expression of bcl-2 was significantly up
      regulated in PLD treatment groups in MLE-12 cells. These results showed that the
      administration of PLD improved ALI both in vivo and in vitro, possibly through
      suppressing apoptosis and inflammation.

PMID- 25981111
TI  - Specific cellular immune response elicited by the necrotic tumor cell-stimulated
      macrophages.
AB  - OBJECTIVE: To determine whether the necrotic tumor cell-stimulated macrophages
      (NTCSM) could elicit specific immune response. METHODS: Mice were immunized with
      the necrotic H22 tumor cell lysate-stimulated macrophages and the specific immune
      responses against the same tumor challenge were examined. The morphologic
      characteristics were observed with the transmission electron microscope and
      scanning electron microscopy. The expression of CD14, CD68, CD80 and CD86 were
      detected with the flow cytometer. The cytotoxicity and cytokine production of
      splenocytes were measured with the MTT assay and ELISA assay respectively.
      RESULTS: Our research results reveal that NTCSMs are larger cells which generally
      generate spherical and elongated protrusions, folding membrane, and vesicles on
      their surface. Also, abundant lysosomes, secondary lysosomes, phagosomes, rough
      endoplasmic reticulum, and lipid bodies were found in their cytoplasm. The flow
      cytometry results show that the necrotic H22 tumor cell lysate could enhance the
      expression of CD14 and CD86 molecules and the NTCSM was characterized by the
      expression of CD14+/-CD68+CD80-CD86+. After the mice were vaccinated with NTCSMs,
      the tumor forming rate, tumor volume and weight of the NTCSM-vaccinated group
      were significantly lower than those of the sterile saline-injected group and
      untreated macrophage-vaccinated group (p<0.05). The cytotoxicity to H22 tumor
      cells of the splenocytes obtained from the NTCSM-immunized group was higher than
      that of the sterile saline-injected group and untreated macrophage-vaccinated
      group (p<0.05). Meanwhile, the levels of IL-2 and IFN-gamma in the culture
      supernatant of the NTCSM-immunized group were higher significantly than those of
      the saline-injected group and untreated macrophage-vaccinated group. The level of
      IL-4 of the NTCSM-immunized group was significantly lower than those of the other
      two groups. CONCLUSION: Our results indicated that NTCSMs could elicit specific
      cellular immune responses in vivo.

PMID- 25981112
TI  - Understanding the mode of action of a pterostilbene derivative as anti
      inflammatory agent.
AB  - Inflammatory response plays an important role not only in the normal physiology,
      but also in the pathology of certain diseases such as cancers. In our previous
      study, we found a novel derivative of pterostilbene (PTER), to be an effective
      inducer of apoptosis in human breast and prostate cancer cells affecting various
      cellular targets. Herein, we further attempted to investigate its anti
      inflammatory potential followed by its probable mode of action. The newly
      developed compound was tested for its anti-inflammatory actions in
      lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced
      rat paw edema models. Our data showed that the derivative inhibited the
      expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
      as well as the downstream products like nitric oxide (NO) and PGE2, at much lower
      doses as compared to PTER. This effect was found to be associated with the
      inhibition of phosphorylation/degradation of IkappaB-alpha and nuclear
      translocation of the p-NFkappaB p65. Moreover, inhibition of mitogen-activated
      protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In
      addition, the newly developed compound also reduced the paw edema, the tissue
      content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues
      after lambda-carrageenan stimulation. Taken together, our findings provide the
      possibility that the PTER derivative might have enhanced cancer chemopreventive
      potential based on its stronger anti-NFkappaB and anti-inflammatory activities as
      compared to its natural counterpart, i.e., PTER. Thus, this compound can be used
      towards the development of an effective anti-inflammatory agent. 

PMID- 25981113
TI  - A case of pediatric Steven-Johnson Syndrome associated with albuterol
      consumption.
AB  - We describe a case of Steven-Johnson Syndrome (SJS) associated with albuterol
      exposure in a 6-year-old male. A possible contributing role of albuterol in SJS
      occurrence in the present case is strongly suggested by the temporal relationship
      between the event and the initiation of drug therapy as well as by the positive
      rechallenge. To the best of our knowledge, albuterol had not been previously
      associated with SJS in medical literature. It can be therefore possible that
      physicians, pediatricians in particular, probably not aware of the possible risk
      of albuterol-induced SJS, might underestimate skin reactions in children taking
      the drug, thus underreporting this kind of severe adverse drug reaction. 

PMID- 25981114
TI  - Further proof of the existence of a non-neuronal cholinergic system in the human
      Achilles tendon: Presence of the AChRalpha7 receptor in tendon cells and cells in
      the peritendinous tissue.
AB  - Human tendon cells have the capacity for acetylcholine (ACh) production. It is
      not known if the tendon cells also have the potential for ACh breakdown, nor if
      they show expression of the nicotinic acetylcholine receptor AChRalpha7
      (alpha7nAChR). Therefore, tendon tissue specimens from patients with midportion
      Achilles tendinopathy/tendinosis and from normal midportion Achilles tendons were
      examined. Reaction for the degradative enzyme acetylcholinesterase (AChE) was
      found in some tenocytes in only a few tendinopathy tendons, and was never found
      in those of control tendons. Tenocytes displayed more regularly alpha7nAChR
      immunoreactivity. However, there was a marked heterogeneity in the degree of this
      reaction within and between the specimens. alpha7nAChR immunoreactivity was
      especially pronounced for tenocytes showing an oval/widened appearance. There was
      a tendency that the magnitude of alpha7nAChR immunoreactivity was higher in
      tendinopathy tendons as compared to control tendons. A stronger alpha7nAChR
      immunoreactivity than seen for tenocytes was observed for the cells in the
      peritendinous tissue. It is likely that the alpha7nAChR may be an important part
      of an auto-and paracrine loop of non-neuronal ACh that is released from the
      tendon cells. The effects may be related to proliferative and blood vessel
      regulatory functions as well as features related to collagen deposition. ACh can
      furthermore be of importance in leading to anti-inflammatory effects in the
      peritendinous tissue, a tissue nowadays considered to be of great relevance for
      the tendinopathy process. Overall, the findings show that tendon tissue, a tissue
      known to be devoid of cholinergic innervation, is a tissue in which there is a
      marked non-neuronal cholinergic system. 

PMID- 25981115
TI  - SPINK1 mutation in a pediatric patient with chronic pancreatitis: A case report.

PMID- 25981116
TI  - SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells
      via deacetylation of FOXO3.
AB  - Cigarette smoking plays an important role in increased incidence of chronic
      obstructive pulmonary disease (COPD). The underlying mechanism in which cigarette
      smoking induced impairment of lung epithelial cells is still unknown. SIRT5 is a
      nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, which has
      been implicated in the regulation of metabolism, stress responses, and aging.
      Forkhead box O3 (FOXO3) belongs to the O subclass of the forkhead family of
      transcription factors. It is also involved in protection from oxidative stress by
      upregulating antioxidants in epithelial cells. Here, we show that cigarette smoke
      extract (CSE) induces SIRT5 to deacetylate FOXO3 at K271 and K290. Deacetylation
      of FOXO3 promotes its nuclear localization. Notably, transfection with FOXO3
      K271R- or K290R-attenuated CSE-induced apoptosis in SIRT5 knocked down cells,
      suggesting the protective effects of SIRT5, is mediated by FOXO3. In contrast,
      CSE stress upregulates SIRT5, which activates FOXO3alpha leading to rescuing
      apoptosis. Thus, SIRT5 constitutes a determinant of apoptosis by CSE in lung
      epithelial cells. 

PMID- 25981117
TI  - Spatial characteristics of evoked potentials elicited by a MEMS microelectrode
      array for suprachoroidal-transretinal stimulation in a rabbit.
AB  - BACKGROUND: Suprachoroidal-transretinal stimulation (STS) can potentially restore
      vision. This study investigated the spatial characteristics of cortical
      electrical evoked potentials (EEPs) elicited by STS. METHODS: A 4 * 4 thin-film
      platinum microelectrode stimulating array (200 MUm electrode diameter and 400 MUm
      center-to-center distance) was fabricated by a micro-electro-mechanical systems
      (MEMS) techniques and implanted into the suprachoroidal space of albino rabbits.
      RESULTS: The current threshold to elicit reliable EEPs by a single electrode was
      41.6 +/- 12.6 MUA, corresponding to a 66.2 +/- 20.1 MUC . cm(-2) charge density
      per phase, which was lower than the reported safety limits. Spatially
      differentiated cortical responses could be evoked by STS through different rows
      or columns of electrical stimulation; furthermore, shifts in the location of the
      maximum cortical activities were consistent with cortical visuotopic maps;
      increasing the number of simultaneously stimulating electrodes increased the
      response amplitudes of EEPs and expanded the spatial spread as well. In addition,
      long-term implantation and electrical stimulation of the MEMS electrode array in
      suprachoroidal space are necessary to evaluate systematically the safety and
      biocompatibility of this approach. CONCLUSIONS: This study indicates that the STS
      approach by a MEMS-based platinum electrode array is a feasible alternative for
      visual restoration, and relatively high spatial discrimination may be achieved.

PMID- 25981118
TI  - Intravitreal inhibition of complement C5a reduces choroidal neovascularization in
      mice.
AB  - PURPOSE: To investigate the influence of complement component C5a inhibition on
      laser-induced choroidal neovascularization (CNV) in mice using a C5a specific L
      aptamer. METHODS: In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor
      (NOX-D20) was intravitreally injected in three concentrations: 0.3, 3.0, and 30
      mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 mg/ml; the
      vehicle (5 % glucose) was injected in controls. Vascular leakage was evaluated
      using fluorescence angiography, CNV area was examined immunohistochemically.
      Activated immune cells surrounding the CNV lesion and potential cytotoxicity were
      analyzed. RESULTS: Compared to controls, CNV areas were significantly reduced
      after NOX-D20 injection at a concentration of 0.3 and 3.0 mg/ml (p = 0.042; p =
      0.016). NOX-D20001 significantly decreased CNV leakage but not the area (p =
      0.007; p = 0.276). At a concentration of 30 mg/ml, NOX-D20 did not reveal
      significant effects on vascular leakage or CNV area (p = 0.624; p = 0.121). The
      amount of CD11b positive cells was significantly reduced after treatment with 0.3
      and 3.0 mg/ml NOX-D20 (p = 0.027; p = 0.002). No adverse glial cell proliferation
      or increased apoptosis were observed at effective dosages. CONCLUSIONS: Our
      findings demonstrate that the targeted inhibition of complement component C5a
      reduces vascular leakage and neovascular area in laser-induced CNV in mice. NOX
      D20 was proven to be an effective and safe agent that might be considered as a
      therapeutic candidate for CNV treatment. The deficiency of activated immune cells
      highlights promising new aspects in the pathology of choroidal
      neovascularization, and warrants further investigations.

PMID- 25981119
TI  - Effects of mydriasis and miosis on kinetic perimetry findings in normal
      participants.
AB  - PURPOSE: To evaluate the effects of pharmacologically induced mydriasis and
      miosis on kinetic perimetry findings in normal participants. METHODS: Thirty
      eight eyes of 38 healthy young participants underwent kinetic perimetry (Octopus
      900 perimeter) with III4e, I4e, I3e, I2e, and I1e stimuli. For each participant,
      24 predetermined meridians with 15 degrees  intervals were automatically tested
      with a velocity of 3 degrees /s under normal, mydriatic, and miotic conditions.
      Mydriasis and miosis were induced by one drop of 0.4 % tropicamide and 2 %
      pilocarpine hydrochloride, respectively. The isopter area and kinetic sensitivity
      were compared between the three pupil conditions. RESULTS: The average pupil size
      in the normal condition was 5.6 +/- 0.9 mm, and it significantly increased to 8.5
      +/- 0.7 mm after mydriasis (p < 0.01) and decreased to 3.4 +/- 0.8 mm after
      miosis (p < 0.01). Compared to the normal pupil, the isopter area of the dilated
      pupil was not significantly different under the III4e stimulus; however, it
      significantly decreased under the I4e, I3e, I2e, and I1e stimuli (p < 0.01).
      Compared to the normal pupil, the isopter area of the constricted pupil
      significantly decreased (p < 0.01) with the III4e stimulus and significantly
      increased with the I3e and I2e stimuli (p < 0.05). CONCLUSIONS: For both pupil
      conditions, kinetic sensitivity at each meridian showed a similar trend to the
      isopter area under each stimulus. The isopter area of the dilated pupil generally
      decreased, whereas the isopter area of the constricted pupil showed various
      findings. Therefore, careful attention should be paid to changes in the isopter
      area associated with changes in the pupil size.

PMID- 25981120
TI  - Birth-related retinal hemorrhages in healthy full-term newborns and their
      relationship to maternal, obstetric, and neonatal risk factors.
AB  - PURPOSE: The purpose was to explore underlying maternal, obstetric, and neonatal
      risk factors of retinal hemorrhages (RH) in healthy full-term newborns. METHODS:
      A total of 1199 full-term infants, with gestational age more than 37 weeks and
      Apgar score of 7 or above, were included in this study. Infants with severe
      systemic diseases or any other eye diseases were excluded. Eye examinations with
      RetCamIII within 1 week of birth were performed in all infants. Maternal,
      obstetric, and neonatal parameters were analyzed and compared between newborns
      with RH and those without RH. RESULTS: RH was seen in 294 of the 1199 infants
      (24.5 %) in this study. Among factors examined in the study, spontaneous vaginal
      delivery (SVD) (odds ratio [OR] =3.811 [95 % CI2.649-5.483], P < 0.001) and
      cephalhematoma (OR = 1.823 [95 % CI1.009-3.296], P = 0.047) correlated positively
      with RH occurrence in newborns, while a history of cesarean delivery correlated
      negatively with RH occurrence (OR = 0.296 [95 % CI0.139-0.630], P = 0.002). There
      was no statistical correlation found between RH and the other risk factors
      examined in this study. These factors included gender, gestational age, birth
      weight, maternal age, volume, and turbidity of amniotic fluid, duration of the
      first or second stage of labor, anemia, hypertensive disorders complicating
      pregnancy (HDCP), fetal distress, intracranial hemorrhage, and neonatal
      hyperbilirubinemia. CONCLUSIONS: RH is common in full-term newborns. A lower
      prevalence of newborn RH was found in infants delivered by mothers with a history
      of cesarean delivery. In contrast, SVD and cephalhematoma were found to be
      potential risk factors for the development of newborn RH in full-term infants.
      Infants with these risk factors may, therefore, require greater attention in
      regard to RH development.

PMID- 25981121
TI  - Bone augmentation of the osteo-odonto alveolar lamina in MOOKP--will it delay
      laminar resorption?
AB  - PURPOSE: We aimed to describe a new technique and analyse the early outcomes of
      augmenting the canine tooth using a mandibular bone graft in an attempt to delay
      or retard the process of laminar resorption following the modified osteo odonto
      keratoprosthesis (MOOKP) procedure. DESIGN: This was a retrospective case series.
      PATIENTS AND METHODS: Eyes that underwent the bone augmentation procedure between
      December 2012 and February 2014 were retrospectively analysed. The procedure,
      performed by the oromaxillofacial surgeon, involved securing a mandibular bone
      graft beneath the periosteum on the labial aspect of the canine tooth chosen to
      be harvested for the MOOKP procedure. This procedure was performed simultaneously
      with the Stage 1 A of the MOOKP. Three months later, the tooth was harvested and
      fashioned into the osteo-odonto alveolar lamina similar to the method described
      in the Rome-Vienna Protocol. RESULTS: The bone augmentation procedure was
      performed in 11 eyes (five SJS/ six chemical injuries). The mean follow-up after
      Stage 2 of MOOKP procedure in these eyes was 7.45 months (2 to 20 months).
      Complications noted were peripheral laminar exposure (three eyes-SJS) and bone
      graft exposure and necrosis in the mouth (nine-SJS). No evidence of clinical
      laminar resorption was noted in any of the eyes. CONCLUSION: Laminar resorption
      in MOOKP can lead to vision and globe threatening complications due to the
      consequent cylinder instability and chances of extrusion. Augmenting the bone on
      the labial aspect of the canine tooth might have a role to play in delaying or
      preventing laminar resorption.

PMID- 25981122
TI  - Socioeconomic differences in the prevalence, awareness, and control of diabetes
      in Bangladesh.
AB  - AIMS: To explore the association of the socioeconomic status (SES) in Bangladesh
      with diabetes prevalence, awareness, and control. METHODS: A population sample of
      7540 individuals from the 2011 Bangladesh Demographic Health Survey was used. A
      composite variable of education and wealth calculated the SES indicator. Besides
      prevalence (age-sex adjusted) of diabetes and pre-diabetes, three other points
      were analyzed with the socio-demographic characteristics: awareness of diabetes,
      diabetics receiving medication and adequacy of treatment (measured by achieving
      normal fasting plasma glucose). RESULTS: The age-sex adjusted prevalence of
      diabetes and pre-diabetes were 10.8% and 25.0%, respectively, in the study
      population (n=7540). Prevalence of diabetes was 7.2% in the low SES (n=2147) and
      17.9% in the high SES group (n=2,418). Among diabetics (n=879), 39.7% were aware
      of their disease, 35.5% were receiving medication, and 13.0% were receiving
      adequate medication. Diabetic patients from the medium or high SES group had an
      increased likelihood of being aware of their disease and of receiving medication.
      CONCLUSIONS: Contrary to other developed countries, diabetes in Bangladesh is
      more prevalent among the higher SES group. Due to the high prevalence of pre
      diabetes, lack of awareness of diabetes and less likelihood of receiving adequate
      treatment in lower SES group, there is potential for the rapid increase of
      diabetes. Urgent preventive measures are needed to control the impending diabetes
      epidemic.

PMID- 25981123
TI  - Insulin glargine compared with premixed insulin for management of insulin-naive
      type 2 diabetes patients uncontrolled on oral antidiabetic drugs: the open-label,
      randomized GALAPAGOS study.
AB  - AIMS: Demonstrate superiority of insulin glargine (+/-glulisine) strategy versus
      premixed insulin strategy for percentage of patients reaching HbA1c <7% (<53
      mmol/mol) at study end without any documented symptomatic hypoglycemia (bloof
      glucose [BG] <=3.1 mmol/L) in type 2 diabetes (T2DM) patients failing oral
      agents. METHODS: This 24-week, open-label, multinational trial randomized
      patients to glargine OD or premix OD or BID, continuing metformin +/- insulin
      secretagogue (IS). Second premix injection could be added any time; glulisine
      could be added with main meal in glargine OD patients with HbA1c >=7% and fasting
      blood glucose (FBG) <7 mmol/L at week 12. IS was stopped with any second
      injection. Insulin titration targeted FBG <=5.6 mmol/L. RESULTS: Modified intent
      to-treat population comprised 923 patients (glargine, 462; premix, 461). Baseline
      characteristics were similar (mean T2DM duration: 9 years; HbA1c: 8.7% (72
      mmol/mol); FBG: 10.4 mmol/L). Primary endpoint was achieved by 33.2% of glargine
      (+/-glulisine) and 31.4% of premix patients. Superiority was not demonstrated,
      but non-inferiority was (pre-specified margin: 25% of premix rate). More patients
      using premix achieved target (52.6% vs. 43.2%, p=0.005); symptomatic hypoglycemia
      was less with glargine (1.17 vs. 2.93 events/patient-year). CONCLUSIONS: Glargine
      (+/-glulisine) and premix strategies resulted in similar percentages of well
      controlled patients without hypoglycemia, with more patients achieving target
      HbA1c with premix whereas overall symptomatic hypoglycemia was less with
      glargine.

PMID- 25981124
TI  - CGAT: a model for immersive personalized training in computational genomics.
AB  - How should the next generation of genomics scientists be trained while
      simultaneously pursuing high quality and diverse research? CGAT, the
      Computational Genomics Analysis and Training programme, was set up in 2010 by the
      UK Medical Research Council to complement its investment in next-generation
      sequencing capacity. CGAT was conceived around the twin goals of training future
      leaders in genome biology and medicine, and providing much needed capacity to UK
      science for analysing genome scale data sets. Here we outline the training
      programme employed by CGAT and describe how it dovetails with collaborative
      research projects to launch scientists on the road towards independent research
      careers in genomics. 

PMID- 25981126
TI  - Population genetics of autopolyploids under a mixed mating model and the
      estimation of selfing rate.
AB  - Nowadays, the population genetics analysis of autopolyploid species faces many
      difficulties due to (i) limited development of population genetics tools under
      polysomic inheritance, (ii) difficulties to assess allelic dosage when genotyping
      individuals and (iii) a form of inbreeding resulting from the mechanism of
      'double reduction'. Consequently, few data analysis computer programs are
      applicable to autopolyploids. To contribute bridging this gap, this article first
      derives theoretical expectations for the inbreeding and identity disequilibrium
      coefficients under polysomic inheritance in a mixed mating model. Moment
      estimators of these coefficients are proposed when exact genotypes or just
      markers phenotypes (i.e. allelic dosage unknown) are available. This led to the
      development of estimators of the selfing rate based on adult genotypes or
      phenotypes and applicable to any even-ploidy level. Their statistical
      performances and robustness were assessed by numerical simulations. Contrary to
      inbreeding-based estimators, the identity disequilibrium-based estimator using
      phenotypes is robust (absolute bias generally < 0.05), even in the presence of
      double reduction, null alleles or biparental inbreeding due to isolation by
      distance. A fairly good precision of the selfing rate estimates (root mean
      squared error < 0.1) is already achievable using a sample of 30-50 individuals
      phenotyped at 10 loci bearing 5-10 alleles each, conditions reachable using
      microsatellite markers. Diallelic markers (e.g. SNP) can also perform
      satisfactorily in diploids and tetraploids but more polymorphic markers are
      necessary for higher ploidy levels. The method is implemented in the software
      SPAGeDi and should contribute to reduce the lack of population genetics tools
      applicable to autopolyploids.

PMID- 25981125
TI  - Phosphate ions and glutaminyl cyclases catalyze the cyclization of glutaminyl
      residues by facilitating synchronized proton transfers.
AB  - Phosphate ions and glutaminyl cyclase (QC) both catalyze the formation of
      pyroglutamate (pE, pGlu) from N-terminal glutamine residues of peptides and
      proteins. Here, we studied the mechanism of glutamine cyclization using kinetic
      secondary deuterium and solvent isotope effects. The data suggest that proton
      transfer(s) are rate determining for the spontaneous reaction, and that phosphate
      and QC are accelerating the reaction by promoting synchronized proton transfers
      in a concerted mechanism. Thus, non-enzymatic and enzymatic catalysis of
      pyroglutamate formation exploit a similar mode of transition-state stabilization.

PMID- 25981127
TI  - Increasing Autism Awareness in Inner-City Churches: A Brief Report.
AB  - Autism diagnosis rates trail significantly in the African American community.
      This pre-test post-test pilot study evaluated an African American inner-city
      church health ambassadors (HAs) autism spectrum disorder (ASD) awareness training
      session. The participants included 12 HAs who attended the 1 hour training
      session organized by the National Baptist Convention, USA, Inc. Results of
      surveys showed higher mean scores post training for (1) HA attitudes about the
      potential for children to improve with applied behavior analysis therapy; (2) HA
      self-efficacy for having information about ASD screening materials; (3)
      strategies HAs could use to help parents/caregivers of children with
      developmental delays and challenging behaviors; (4) HA confidence in referrals
      for children with signs of ASD; (5) HA knowledge of measures to take to maximize
      a child's chance of receiving an ASD evaluation; and (6) HA comfort for talking
      to parents about children with challenging behaviors. Several of these effects
      were maintained 3 months later. Findings underscore the usefulness of the
      intervention for increasing the dissemination of knowledge about ASD and the
      opportunity to positively affect ASD screening, early intervention, and policy
      standards applicable to this vulnerable population.

PMID- 25981128
TI  - Implantable drug delivery systems should be inserted outside radiation therapy
      fields in breast cancer patients.

PMID- 25981129
TI  - Designing a ridge filter based on a mouse foot skin reaction to spread out Bragg
      peaks for carbon-ion radiotherapy.
AB  - BACKGROUND AND PURPOSE: Carbon-ion radiotherapy uses spread-out Bragg peaks
      (SOBP) to produce uniform biological effects within a target volume. The relative
      biological effectiveness is determined by the in vitro cell kill after a single
      dose is employed to design the SOBP. A question remains as to whether biological
      effects for in vivo tissues after fractionated doses are also uniform within the
      SOBP. MATERIAL AND METHODS: Mouse foot skin was irradiated with fractionated
      doses of carbon ions at various linear energy transfer (LET) values. A new ridge
      filter was designed based on alpha and beta values for each LET to cause moderate
      skin reaction, and was studied concerning its uniformity. RESULTS: The reciprocal
      total doses of intermediate-LET carbon ions and of reference gamma rays linearly
      increased with an increase of a dose per fraction in Fe-plots. As the single
      total dose of higher LET run off linearity, data obtained from 2 to 6 fractions
      were used to design a new ridge filter. The physical dose distribution of the new
      ridge filter was almost identical to, and indistinguishable from, the ridge
      filter designed based on the in vitro cell kill. CONCLUSIONS: The LET dependence
      of alpha is a principle of the biological factor to be used for designing spread
      out Bragg peaks of carbon-ion radiotherapy.

PMID- 25981131
TI  - Re: Impact of comorbidity in staging & management decision making of
      nasopharyngeal Ca (NPC).

PMID- 25981130
TI  - Bone marrow sparing in intensity modulated proton therapy for cervical cancer:
      Efficacy and robustness under range and setup uncertainties.
AB  - BACKGROUND AND PURPOSE: This study evaluates the potential efficacy and
      robustness of functional bone marrow sparing (BMS) using intensity-modulated
      proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic
      toxicity. MATERIAL AND METHODS: IMPT plans with prescription dose of 45 Gy were
      generated for ten patients who have received BMS intensity-modulated X-ray
      therapy (IMRT). Functional bone marrow was identified by (18)F-flourothymidine
      positron emission tomography. IMPT plans were designed to minimize the volume of
      functional bone marrow receiving 5-40 Gy while maintaining similar target
      coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with +/
      3% range uncertainty errors and/or +/-3 mm translational setup errors in all
      three principal dimensions. RESULTS: In the static scenario, the median dose
      volume reductions for functional bone marrow by IMPT were: 32% for V(5Gy), 47%
      for V(10Gy), 54% for V(20Gy), and 57% for V(40Gy), all with p<0.01 compared to
      IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for
      V(5Gy), 37% for V(10Gy), 41% for V(20Gy), and 39% for V(40Gy), all with p<0.01.
      CONCLUSIONS: The potential sparing of functional bone marrow by IMPT for cervical
      cancer is significant and robust under realistic systematic range uncertainties
      and clinically relevant setup errors.

PMID- 25981132
TI  - Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose,
      the radiation dose and the integrity of the homologous recombination pathway of
      tumor cells.
AB  - BACKGROUND AND PURPOSE: The PARP inhibitor olaparib is currently tested in
      clinical phase 1 trials to define safe dose levels in combination with RT.
      However, certain clinically relevant insights are still lacking. Here we test,
      while comparing to single agent activity, the olaparib dose and genetic
      background dependence of olaparib-mediated radiosensitization. MATERIALS AND
      METHODS: Long-term growth inhibition and clonogenic assays were used to assess
      radiosensitization in BRCA2-deficient and BRCA2-complemented cells and in a panel
      of human head and neck squamous cell carcinoma cell lines. RESULTS: The extent of
      radiosensitization greatly depended on the olaparib dose, the radiation dose and
      the homologous recombination status of cells. Olaparib concentrations that
      resulted in radiosensitization prevented PAR induction by irradiation. Seven
      hours olaparib exposures were sufficient for radiosensitization. Importantly, the
      radiosensitizing effects can be observed at much lower olaparib doses than the
      single agent effects. CONCLUSION: Extrapolation of these data to the clinic
      suggests that low olaparib doses are sufficient to cause radiosensitization,
      underlining the potential of the treatment. Here we show that drug doses
      achieving radiosensitization can greatly differ from those achieving single agent
      activities, an important consideration when developing combined radiotherapy
      strategies with novel targeted agents.

PMID- 25981133
TI  - Homologs to Cry toxin receptor genes in a de novo transcriptome and their altered
      expression in resistant Spodoptera litura larvae.
AB  - Insect resistance threatens sustainability of insecticides based on Cry proteins
      from the bacterium Bacillus thuringiensis (Bt). Since high levels of resistance
      to Cry proteins involve alterations in Cry-binding midgut receptors, their
      identification is needed to develop resistance management strategies. Through
      Illumina sequencing we generated a transcriptome containing 16,161 annotated
      unigenes for the Oriental leafworm (Spodoptera litura). Transcriptome mining
      identified 6 contigs with identity to reported lepidopteran Cry toxin receptors.
      Using PCR we confirmed their expression during the larval stage and compared
      their quantitative expression in larvae from susceptible and a field-derived
      Cry1Ca resistant strain of S. litura. Among reduced transcript levels detected
      for most tested contigs in the Cry1Ca-resistant S. litura larvae, the most
      dramatic reduction (up to 99%) was detected for alkaline phosphatase contigs.
      This study significantly expands S. litura transcriptomic resources and provides
      preliminary identification of putative receptor genes with altered expression in
      S. litura resistant to Cry1Ca toxin. 

PMID- 25981134
TI  - Impacts of Nosema sp. (Microsporidia: Nosematidae) on the sugarcane borer,
      Diatraea saccharalis (Lepidoptera: Crambidae).
AB  - In Brazil, the sugarcane borer, Diatraea saccharalis (Fabricius, 1794)
      (Lepidoptera: Crambidae), is controlled with massive releases of the hymenopteran
      parasitoid Cotesia flavipes Cam. (Hymenoptera: Braconidae); over 3 million
      hectares of sugarcane are treated annually with 18 billion parasitoids. In order
      to meet this demand, parasitoids are produced in D. saccharalis under laboratory
      conditions where a Nosema sp. is reported to be an important problem in mass
      rearing of the host. The goals for this work were to study the pathogenicity of
      the Nosema sp. and the progression of the disease in the host under laboratory
      conditions. The average median lethal time (LT50) of Nosema sp. in first instar
      D. saccharalis varied from 9 +/- 0.3 to 42 +/- 2.3 days at concentration of 5 *
      10(5)-0.5 spores/mm(3) artificial diet (10(7)-10 spores/MUl). For third instar,
      the average of LT50 ranged from 32 +/- 0.7 to 37 +/- 0.7 days at concentration of
      5 * 10(5)-5 * 10(2) spores/mm(3) artificial diet (10(7)-10(4) spores/MUl in
      saline). The concentration necessary to cause 50% mortality (LC50) of first
      instar larvae was 5.6 (0.9-17.6) spores/MUl and the estimated LC50 for third
      instar larvae was 1,200 (200-4700) spores/MUl. The impacts of Nosema sp. on D.
      saccharalis were analyzed for first instar larvae fed 0.5 spores/mm(3) artificial
      diet. Duration and viability of the larval and pupal stages, adult longevity,
      pupal weight and fertility life table were measured for offspring of mating pairs
      composed of infected females and uninfected males or infected males and
      uninfected females and compared to offspring of uninfected pairs. Nosema sp.
      infection resulted in adverse effects on all biological parameters measured
      except for the duration of the larval and pupal stages and the weight of the male
      pupae, which did not differ statistically between infected and uninfected groups.
      The intrinsic rates of growth (rm) were greater for uninfected pairs compared to
      pairs with either male or female infected. The growth rate of individual larvae
      produced by uninfected adults was 48.2% faster than of larval offspring of
      infected females and it was negative (-0.003) when males were infected. Our study
      confirms the negative impact of the Nosema sp. in mass rearing of D. saccharalis
      for parasitoid production but shows potential for use as a microbial control
      agent of the sugarcane borer.

PMID- 25981135
TI  - Downstaging hepatocellular carcinoma: A systematic review and pooled analysis.
AB  - Downstaging can facilitate liver transplantation (LT) for patients outside of
      Milan criteria with hepatocellular carcinoma (HCC); however, the optimal protocol
      and downstaging outcomes are poorly defined. We aimed to characterize rates of
      successful downstaging to within Milan criteria and post-LT recurrence and
      survival among patients who underwent downstaging. We performed a systematic
      literature review using the MEDLINE and Embase databases from January 1996
      through March 2015 and a search of national meeting abstracts from 2010 to 2014.
      Rates of downstaging success (defined as a decrease of tumor burden to within
      Milan) and post-LT recurrence with 95% confidence intervals (CIs) were
      calculated. Prespecified subgroup analyses were conducted by treatment modality,
      study design, and patient characteristics. Thirteen studies (n = 950 patients)
      evaluating downstaging success had a pooled success rate of 0.48 (95% CI, 0.39
      0.58%). In subgroup analyses, there was no significant difference comparing
      transarterial chemoembolization (TACE) versus transarterial radioembolization
      (TARE; P = 0.51), but there were higher success rates in prospective versus
      retrospective studies (0.68 versus 0.44; P < 0.001). The 12 studies (n = 320
      patients) evaluating post-LT HCC recurrence had a pooled recurrence rate of 0.16
      (95% CI, 0.11-0.23). There was no significant difference in recurrence rates
      between TACE and TARE (P = 0.33). Post-LT survival could not be aggregated
      because of heterogeneity in survival data reporting. Current data have
      heterogeneity in baseline tumor burden, waiting time, downstaging protocols, and
      treatment response assessments. There are also notable limitations including
      inconsistent reporting of inclusion criteria, downstaging protocols, and outcome
      assessment criteria. In conclusion, the success rate of downstaging HCC to within
      Milan criteria exceeds 40%; however, posttransplant HCC recurrence rates are high
      at 16%. Downstaging protocols for HCC should be systematically studied and
      optimized to minimize the risk of post-LT HCC recurrence.

PMID- 25981136
TI  - Self-assessment of clinical nurse mentors as dimensions of professional
      development and the capability of developing ethical values at nursing students:
      A correlational research study.
AB  - INTRODUCTION: Providing adequate training for mentors, fostering a positive
      mentorship culture and establishing the necessary operational procedures for
      ensuring mentorship quality are the keys to effective clinical mentoring of
      nursing students. PURPOSE: The purpose of the research was to explain different
      dimensions of clinical mentors' professional development and their capability of
      developing ethical values in nursing students. METHODS: A non-experimental
      quantitative research design was employed. Data were collected by means of a
      questionnaire administered to the population of clinical mentors (N=143). The
      total number of questions was 36. Descriptive statistics were used, and bivariate
      analysis, factor analysis, correlation analysis and linear regression analysis
      were performed. RESULTS: The professional development of clinical nurse mentors
      was explained (R(2)=0.256) by career advancement (p=0.000), research and learning
      (p=0.024) and having a career development plan (p=0.043). Increased professional
      self-confidence (R(2)=0.188) was explained by career advancement (p=0.000) and
      the time engaged in record keeping (p=0.028). Responsibility for the development
      of ethical values in nursing students (R(2)=0.145) was explained by the
      respondents' level of education (p=0.020) and research and learning (p=0.024).
      Applying ethical principles and norms into practice (R(2)=0.212) was explained by
      self-assessed knowledge in ethics (p=0.037) and research and learning (p=0.044).
      CONCLUSIONS: Clinical nurse mentors tended to lack a career development plan, had
      low work time spent on research and insufficiently participated in education and
      training activities, which turned out to be significant explanatory factors of
      their professional development and their capability of developing ethical values
      in nursing students. The research showed that nursing and higher education
      managers often failed to assume responsibility for the professional development
      of clinical nurse mentors.

PMID- 25981137
TI  - Evaluation of dementia education programs for pre-registration healthcare
      students-A review of the literature.
AB  - OBJECTIVES: In an aging society, the number of people living with dementia is
      rapidly increasing. Health care students receive little input on dementia during
      their pre-registration education, hence there is a requirement to improve
      education to work with this client group. The review aimed to focus on education
      on working with people with dementia for pre-registration healthcare students.
      DESIGN: A comprehensive review of the literature. DATA SOURCES: Online databases
      Medline, PsychInfo, CINAHL, Science Direct and PubMed were used. REVIEW METHODS:
      The studies were selected according to the following criteria: main focus on
      education and training on working with people with dementia in pre-registration
      healthcare programs. Reports that described a training program but did not
      include evaluation were excluded. For inclusion, studies had to be published in
      English between January 2007 and March 2014. Identified papers were screened and
      reviewed by the three authors. RESULTS: Nine studies met the inclusion criteria.
      Most studies were based in North America, predominantly in nursing and medical
      education. Educational interventions chiefly aimed to improve students'
      knowledge, comfort level and attitudes toward people with dementia. It was shown
      that theoretical input alone did not give students the necessary skills to work
      with people with dementia. Educational interventions were most effective when a
      practice based experience was preceded by theoretical preparation. CONCLUSION:
      Most of the findings were positive, demonstrating the potential to improve
      students' knowledge, attitude and comfort level, however methods and evaluation
      were not always sufficiently reported, making them difficult to use or replicate.
      This review highlights the need for studies with rigorous methods to determine
      evidence based best practice for all those working with people with dementia in
      order to provide effective care and improve their quality of life.

PMID- 25981138
TI  - Direct Oral Anticoagulants (DOACs) in the Laboratory: 2015 Review.
AB  - Direct oral anticoagulant therapies, including direct anti-Xa and thrombin
      inhibitors have recently been introduced and may have advantages over vitamin K
      antagonists such as warfarin. This review describes briefly the clinical utility
      and mechanism of action of these agents. Detailed information is provided on
      effect of these agents on routine assays including the APTT and PT as well as
      their impact on specialty laboratory assays. Also included are the use of drug
      specific assays and a discussion of alternative methods to determine relative
      drug concentration, such as evaluating drug calibrators in APTT and PT assays and
      using heparin calibrated anti-Xa assays to measure direct Xa inhibitors. 

PMID- 25981139
TI  - Residual vein thrombosis and the risk of subsequent serious complications.

PMID- 25981140
TI  - From laboratory to clinical practice: Dabigatran effects on thrombin generation
      and coagulation in patient samples.
AB  - INTRODUCTION: Dabigatran (Dabi) is not routinely monitored. However, in emergency
      cases quantitative assessment is required and laboratories must provide suitable
      tests at all hours. Little is known about Dabi effects on thrombin generation.
      MATERIALS AND METHODS: Patient samples (n=241) were analyzed for functional Dabi
      concentrations (Dabi-TT) using a combination of the Hemoclot Thrombin Inhibitors
      assay (HTI(r)) and, for samples with low levels, undiluted thrombin time (TT).
      Results were compared to prothrombin time (PT) and activated partial
      thromboplastin time (APTT). In 49 samples Dabi effects were further investigated
      with Calibrated Automated Thrombogram (CAT(r)) for thrombin generation and with
      Russell's viper venom time (RVVT), prothrombinase-induced clotting time
      (PiCT(r)), chromogenic Anti-IIa(r) and ecarin clotting assay (ECA(r)). Fibrinogen
      and D dimer were assessed to reflect the coagulation status of the patient. A
      subset of these samples (n=21) were also analyzed by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). RESULTS: Dabi-TT correlated with RVVT (R(2)=0.49),
      PiCT(r) (R(2)=0.73), ECA(r) (R(2)=0.89), Anti-IIa(r) (R(2)=0.90) and LC-MS/MS
      (R(2)=0.81). APTT correlated curvi-linearly with Dabi-TT (R(2)=0.71), but was
      normal in many cases (18/70) despite Dabi-TT>40ng/mL. There was no association
      between Dabi-TT and fibrinogen or D dimer levels. Increasing Dabi concentrations
      prolonged lag time (R(2)=0.54) and, surprisingly, elevated the ETP and Peak of
      CAT(r) (p<0.001). CONCLUSIONS: Thrombin-specific tests measure Dabi accurately,
      whereas coagulation time based assays depend more on other factors. The enhanced
      thrombin generation in Dabi-treated patients may predict clinically relevant
      hypercoagulability and warrants further investigation.

PMID- 25981141
TI  - Congenital hypofibrinogenemia associated with novel homozygous fibrinogen Aalpha
      and heterozygous Bbeta chain mutations.
AB  - We report the molecular characterisation of two novel cases of inherited
      hypofibrinogenemia. After sequencing all coding regions and intron-exon
      boundaries of the three fibrinogen genes (FGA, FGB, and FGG), two different novel
      mutations were found, one homozygous and one heterozygous. The first patient,
      with a mild bleeding history and mild discrepancy between functional and
      immunological fibrinogen, showed a novel homozygous nonsense mutation in exon 5
      of FGA (p.Trp373*, p.Trp354* according to the mature protein) caused by a G>A
      transition at nucleotide position 1,119. The resulting truncation in the Aalpha
      chain is likely to reduce the efficiency of fibrinogen assembly and secretion.
      The second patient, referred after ischemic stroke (functional fibrinogen
      77mg/dL), had a novel heterozygous splicing mutation in intron 5 of FGB
      (IVS5+2T>A or c.832+2T>A), which we demonstrated to cause either exon 5 skipping
      or the inclusion of 75bp belonging to intron 5. Neither splicing defect alters
      the reading frame: one results in a 38-residue deletion and the other in a 25
      residue insertion in the D domain of fibrinogen Bbeta chain. This report confirms
      that genetically determined partial deficiencies of fibrinogen with levels
      greater than 50mg/dL are rarely associated with significant bleeding symptoms and
      that homozygous null mutations removing a significant portion of the Aalpha chain
      may be associated with mild fibrinogen deficiency. 

PMID- 25981142
TI  - Clinical evaluation of laboratory methods to monitor apixaban treatment in
      patients with atrial fibrillation.
AB  - INTRODUCTION: The direct factor-Xa inhibitor apixaban is approved e.g. for the
      prevention of stroke in patients with atrial fibrillation (AF). Although routine
      monitoring of apixaban therapy is currently not recommended, selective monitoring
      could be useful to optimize efficacy and safety in certain clinical situations.
      We studied the exposure and effect of apixaban using different laboratory methods
      in a clinical setting with a well-defined cohort of AF patients. MATERIAL AND
      METHODS: Seventy AF patients (72+/-7.4years, 64 % men, mean CHADS2 score 1.7)
      treated with apixaban 2.5 (n=10) or 5mg BID (n=60). Trough plasma apixaban
      concentrations determined by liquid chromatography-tandem mass-spectrometry (LC
      MS/MS) were compared to the coagulation assays Anti-factor Xa, PT-INR and aPTT.
      RESULTS: The apixaban plasma concentration determined by LC-MS/MS varied more
      than 10-fold overall. The range was between 15-83 and 29-186ng/mL for the 2.5mg
      BID and 5mg BID respectively, with patients receiving 5mg BID having
      significantly higher apixaban concentrations (p<0.001). A strong correlation
      between LC-MS/MS and anti-FXa-assay was found (p<0.001), while aPTT and PT-INR
      were not sensitive enough. There were no significant correlations between gender,
      creatinine clearance, body weight or age and apixaban exposure. CONCLUSIONS: Anti
      FXa-assay performed well upon apixaban concentrations in a normal exposure range.
      Still LC-MS/MS remains the "gold standard" method, covering also low
      concentrations. Compared to clinical trials, we observed relatively lower
      apixaban exposure and a more pronounced difference between high and low dose.
      Additional information regarding apixaban exposure and benefit-risk profile is
      needed in order to individualize treatment.

PMID- 25981143
TI  - Effects of prenatal stress and emotional reactivity of the mother on emotional
      and cognitive abilities in lambs.
AB  - Consequences of prenatal stress on emotional reactivity and cognitive abilities
      in offspring are under-documented in precocial mammals. Here, we investigated to
      what extent emotional reactivity, judgment bias and spatial learning abilities of
      lambs are affected by chronic stress during late pregnancy and by their dams'
      emotional reactivity. The 20 highest-responsive (HR) and 20 lowest-responsive
      (LR) ewes from a population of 120 Romane ewes were selected according to their
      pre-mating reactivity to social isolation in a new environment. Over the final
      third of pregnancy, 10 HR ewes and 10 LR ewes were exposed daily to various
      unpredictable aversive events such as restraint, mixing groups and transport
      while the other 20 selected ewes were not. In a human and an object test,
      prenatally-stressed lambs were more fearful than control lambs, but the prenatal
      stress effect was moderated by the reactivity of the mothers: prenatally-stressed
      lambs from ewes with high emotional reactivity were more affected. Prenatally
      stressed lambs did not perform as well as control lambs in a maze test and showed
      pessimistic-like judgment in a cognitive bias test. Prenatally-stressed lambs
      were thus characterized by a negative affective state with increased fear
      reactions and impaired cognitive evaluation. The development of negative moods
      could have long-lasting consequences on the coping strategies of the lambs in
      response to their rearing conditions.

PMID- 25981144
TI  - Coronary artery fistulas as a cause of angina: How to manage these patients?
AB  - Coronary artery fistulas represent the most common hemodynamically significant
      congenital defect of the coronary arteries and the clinical presentation is
      mainly dependent on the severity of the left-to-right shunt. We describe a case
      of a 55-year-old man with history of chest pain and without history of previous
      significant chest wall trauma or any invasive cardiac procedures. A coronary
      multislice computed tomography showed two large coronary fistulas arising from
      the left anterior descending coronary artery and ending in an angiomatous plexus
      draining into the common pulmonary trunk. Coronary angiography confirmed the CT
      finding and showed a third fistulous communication arising from the sinus node
      artery. Although coronary fistulas are infrequent, they are becoming increasingly
      important because their management and treatment could prevent serious
      complications. The latest guidelines of the American College of
      Cardiology/American Heart Association indicate as Class I recommendation the
      percutaneous or surgical closure for large fistulas regardless of symptoms. In
      this manuscript, we provide a detailed review of the literature on this topic,
      focusing on the clinical management of these patients. 

PMID- 25981145
TI  - Thrombolysis-facilitated primary percutaneous coronary intervention as a
      therapeutic approach to stent thrombosis.
AB  - BACKGROUND: Stent thrombosis is a clinically significant event occurring days to
      weeks or, infrequently, months or years after percutaneous coronary intervention
      (PCI). Current therapeutic approach is immediate PCI aimed to recanalize the
      occluded artery in order to restore flow and diminish irreversible myocardial
      damage. METHODS: We evaluated the coronary patency, TIMI flow and TIMI myocardial
      perfusion grade (TMPG) in 6 patients presenting with STEMI due to stent
      thrombosis treated by thrombolysis followed by immediate PCI. These were compared
      with control patients treated conventionally by primary PCI. RESULTS: Immediate
      or early coronary angiography in the treatment group showed good coronary flow in
      5 of 6 implicated arteries, whereas immediate angiography in the control group
      demonstrated 8 completely occluded coronary arteries of 9 with stent thrombosis.
      The pre-intervention TIMI flow in the control study group was 0.2+/-0.5 (median
      0), and TMPG was 0.1+/-0.3 (median-0) compared with 2.1+/-1.1 (median-2.3,
      p<0.001) and 1.8+/-1.0 (median-2, p<0.001) in the treatment group, respectively.
      This striking difference in the rate of coronary patency, pre-procedural TIMI
      flow and TMPG, however, did not translate into better cardiac function in the
      treatment group. CONCLUSIONS: These findings suggest that thrombolysis
      facilitated PCI may confer benefit and need not be considered contraindicated
      when treating stent thrombosis. This therapeutic approach should be evaluated as
      a viable therapeutic approach to stent thrombosis.

PMID- 25981146
TI  - People with long QT syndrome who have attention deficit hyperactivity disorder
      deserve to be treated properly.

PMID- 25981147
TI  - Complete atrioventricular block after percutaneous device closure of
      perimembranous ventricular septal defect: A single-center experience on 1046
      cases.
AB  - BACKGROUND: Complete atrioventricular block (cAVB) has been deemed a rare
      complication after transcatheter closure for ventricular septal defect (VSD).
      However, this serious event appears to be underrecognized and is worth being
      investigated further. OBJECTIVES: To determine the incidence and predisposing
      factors of cAVB associated with closure of VSD using a modified double-disk
      occluder (MDO). METHODS: From December 21, 2001 to December 31, 2014, 1046
      patients with perimembranous ventricular septal defect underwent percutaneous
      closure using the MDO. Electrocardiography was evaluated before the procedure,
      within 1 week after the procedure, and then at 1, 3, 6, and 12 months and every
      year thereafter. Other baseline and procedural parameters were also evaluated and
      a comparison between patients requiring pacemakers and those not suffering from
      cAVB was done. RESULTS: cAVB occurred in 17 patients (1.63%) after the procedure.
      Of the 17 patients, 8 underwent permanent pacemaker (PPM) implantation. The cAVB
      occurred within 30 days after the procedure in 14 patients and after 1 year in 3
      patients. In comparison patients aged <=18 years, patients aged >18 years were
      more prone to cAVB (P = .025). Logistic regression revealed no significant
      parameter to predict later requirement for PPM. CONCLUSIONS: The incidence of
      cAVB after transcatheter closure of VSD was acceptable, as part of the cAVB
      population recovered after administration of corticosteroid and application of a
      temporary pacemaker. Late cAVB (>1 year) appears to make it more difficult to
      restore normal conduction block. Because of the recurrence of cAVB, life-long
      follow-up with periodic electrocardiography examination may be mandatory.

PMID- 25981148
TI  - HRS Expert Consensus Statement on remote interrogation and monitoring for
      cardiovascular implantable electronic devices.

PMID- 25981149
TI  - HRS/NSA 2014 survey of atrial fibrillation and stroke: Gaps in knowledge and
      perspective, opportunities for improvement.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) is substantial and
      increasing. Stroke is common in AF and can have devastating consequences. Oral
      anticoagulants are effective in reducing stroke risk, but are underutilized.
      OBJECTIVE: We sought to characterize the impact of stroke on AF patients and
      their caregivers, gaps in knowledge and perspective between physicians and
      patients, and barriers to effective communication and optimal anticoagulation
      use. METHODS: A survey was administered to AF patients with and without history
      of stroke, caregivers of stroke survivors, and physicians across the range of
      specialties caring for AF and stroke patients. RESULTS: While AF patients (n =
      499) had limited knowledge about stroke, they expressed great desire to learn
      more and take action to reduce their risk. They were often dissatisfied with the
      education they had received and desired high-quality written materials. Stroke
      survivors (n = 251) had poor functional outcomes and often underestimated the
      burden of caring for them. Caregivers (n = 203) also wished they had received
      more information about reducing stroke risk before their survivor's event. They
      commonly felt overwhelmed and socially isolated. Physicians (n = 504) did not
      prescribe anticoagulants as frequently as recommended by guidelines. Concerns
      about monitoring anticoagulation and patient compliance were commonly reported
      barriers. Physicians may underestimate patient willingness to take
      anticoagulants. CONCLUSION: We identified significant knowledge gaps among
      patients, caregivers, and physicians in relation to AF and stroke. Furthermore,
      gaps in perspective often lead to suboptimal communication and decision making.
      Increased education and better communication between all stakeholders are needed
      to reduce the impact of stroke in AF.

PMID- 25981150
TI  - Anatomical variation and its management in transplantation.
AB  - Variant anatomy may be challenging at retrieval, with failure to identify
      variance being associated with organ damage, particularly vascular damage. On
      implantation, some variants demand nonstandard techniques of reconstruction or
      implantation. This review covers the common and less common anatomical variants
      of the liver, kidney and pancreas, and gives guidance as to how they may be
      managed during organ retrieval and implantation. 

PMID- 25981151
TI  - Gender differences in the roles for social support in ensuring adequate fruit and
      vegetable consumption among older adult Canadians.
AB  - BACKGROUND: Adequate fruit and vegetable consumption has been linked to
      reductions in all-cause mortality, stroke, and cancer. Unfortunately, less than
      half of Canadians aged 65+ meet the standard international guideline for adequate
      consumption (>=5 servings per day). Among older adults, social isolation and low
      social support are barriers to proper nutrition, but the effects of specific
      types of social support on adequate fruit and vegetable consumption are unknown.
      OBJECTIVE: This study sought to test hypotheses regarding direct and indirect
      pathways through which tangible and emotional/informational social support may
      facilitate adequate fruit and vegetable consumption among older adults. METHODS:
      Analyzing 2008-2009 Canadian Community Health Survey - Healthy Aging component
      data (n = 14,221), logistic regression models were developed to examine
      associations between tangible and emotional/informational social support, eating
      behaviors (eating alone and preparing one's own meals), and meeting the
      recommended guideline of consuming >=5 servings of fruit and vegetables per day.
      RESULTS: In pooled models, emotional/informational support was positively
      associated with adequate fruit and vegetable consumption (OR = 1.16; 95% CI =
      1.07, 1.27). Among men, neither social support form was directly or indirectly
      associated with adequate consumption; among women, adequate consumption was
      negatively associated with tangible support but positively associated with higher
      emotional/informational support. Both of these associations were mediated by not
      usually cooking one's own meals. CONCLUSIONS: Programs and policies that seek to
      foster social support for older adults as a means of ensuring proper nutrition
      should consider the nuanced mechanisms through which different social support
      forms may operate for men and women.

PMID- 25981152
TI  - Eating in the absence of hunger in college students.
AB  - Nearly one-third of college students are overweight or obese. Disinhibited
      eating, a phenomenon defined as the lack of self-restraint over food consumption
      prompted by emotional or external factors, is prevalent among college students
      and may be a target for intervention in this population. Eating in the absence of
      hunger (EAH) is a form of disinhibited eating that has been studied extensively
      in children and adolescents, but there is little investigation of EAH among
      college students. In this research, a validated measure for assessing continual
      and beginning EAH in children and adolescents was modified and assessed in a free
      living college population (n = 457; 84% F; 24.5 +/- 7.6 years; 23.4 +/- 4.8
      kg/m(2)). Nine subscales grouped into three latent factors (emotion, external,
      and physical) accounted for 68% of the variance in continual EAH, and a separate
      set of nine subscales grouped into the same latent factors accounted for 71% of
      the variance in beginning EAH (Cronbach's alpha: 0.82 for continual EAH and 0.81
      for beginning EAH). Female sex and sedentary behavior were significantly related
      to continual EAH, relationships driven by scores for the emotion factor, and to
      beginning EAH, relationships driven by scores for the physical factor. BMI was
      weakly related to the emotion factor (p = 0.06) for continuing EAH only. The
      observation that a sedentary lifestyle was associated to EAH (both continuing and
      beginning EAH) in a college population is a novel finding and reveals a possible
      strategy to moderate EAH.

PMID- 25981153
TI  - Catamenial pneumothorax due to solitary localization of diaphragmatic
      endometriosis.
AB  - INTRODUCTION: Catamenial pneumothorax (CP) is a spontaneous recurrent
      pneumothorax occurring in women in reproductive age. The etiology of CP has been
      associated with thoracic endometriosis and is its most common presentation.
      PRESENTATION OF CASE: A case of right catamenial pneumothorax in a 38 year old
      woman is presented in which three episodes of CP occurred within 72h of menses in
      a 6 month period. The patient underwent videothoracoscopy that revealed a
      solitary localization of diaphragmatic endometriosis. After surgical pleurodesis
      and based on final pathology of resected lesion, hormonal treatment was started.
      The outcome was uneventful and the patients is symptom-free at 6 months.
      DISCUSSION: Catamenial pneumothorax (CP) is a rare clinical entity characterized
      by lung collapse during menstruation, believed to be secondary to pleural
      endometriosis. Nearly all catamenial pneumothorax occur on the right side as
      pleural lesions are almost exclusively right-sided. Diagnostic imaging is based
      on high resolution computed tomography (HRCT) and, preferably, magnetic resonance
      imaging (MRI) since it is able to detect the blood products in the endometrial
      deposits. However the lack of macroscopic findings at surgery makes this
      condition still under-diagnosed. Based on the solitary diaphragmatic localization
      of endometriosis in our case we preferred to limit surgery to videothoracoscopic
      pleurodesis and start hormonal treatment with successful outcome. CONCLUSION:
      Catamenial pneumothorax is the most common presentation of thoracic endometriosis
      syndrome and should always be suspected in women in childbearing age. Treatment
      option are still debated but best results are achieved by videothoracoscopic
      pleurodesis combined with hormonal therapy.

PMID- 25981154
TI  - Computation assisted design of favored composition for ternary Mg-Cu-Y metallic
      glass formation.
AB  - With the aid of ab initio calculations, a realistic interatomic potential was
      constructed for the Mg-Cu-Y ternary system under the proposed formalism of
      smoothed and long-range second-moment approximation of tight-binding. Taking the
      potential as the starting base, an atomistic computation/simulation route was
      developed for designing favored and optimized compositions for Mg-Cu-Y metallic
      glass formation. Simulations revealed that the physical origin of metallic glass
      formation is the collapse of crystalline lattice when solute concentration
      exceeds a critical value, thus leading to predict a hexagonal region in the Mg-Cu
      Y composition triangle, within which metallic glass formation is energetically
      favored. It is proposed that the hexagonal region can be defined as the intrinsic
      glass formation region, or quantitative glass formation ability of the system.
      Inside the hexagonal region, the driving force for formation of each specific
      glassy alloy was further calculated and correlated with its forming ability in
      practice. Calculations pinpointed the optimized stoichiometry in the Mg-Cu-Y
      system to be Mg64Cu16Y20, at which the formation driving force reaches its
      maximum, suggesting that metallic glasses designed to have compositions around
      Mg64Cu16Y20 are most stable or easiest to obtain. The predictions derived
      directly from the atomistic simulations are supported by experimental
      observations reported so far in the literature. Furthermore, Honeycutt-Anderson
      analysis indicated that pentagonal bipyramids (although not aggregating to form
      icosahedra) dominate in the local structure of the Mg-Cu-Y metallic glasses. A
      microscopic picture of the medium-range packing can then be described as an
      extended network of the pentagonal bipyramids, entangled with the fourfold and
      sixfold disclination lines, jointly fulfilling the space of the metallic glasses.

PMID- 25981155
TI  - Kinetics and mechanism of the biodegradation of PLA/clay nanocomposites during
      thermophilic phase of composting process.
AB  - The degradation mechanism and kinetics of polylactic acid (PLA) nanocomposite
      films, containing various commercially available native or organo-modified
      montmorillonites (MMT) prepared by melt blending, were studied under composting
      conditions in thermophilic phase of process and during abiotic hydrolysis and
      compared to the pure polymer. Described first order kinetic models were applied
      on the data from individual experiments by using non-linear regression procedures
      to calculate parameters characterizing aerobic composting and abiotic hydrolysis,
      such as carbon mineralization, hydrolysis rate constants and the length of lag
      phase. The study showed that the addition of nanoclay enhanced the biodegradation
      of PLA nanocomposites under composting conditions, when compared with pure PLA,
      particularly by shortening the lag phase at the beginning of the process. Whereas
      the lag phase of pure PLA was observed within 27days, the onset of CO2 evolution
      for PLA with native MMT was detected after just 20days, and from 13 to 16days for
      PLA with organo-modified MMT. Similarly, the hydrolysis rate constants determined
      tended to be higher for PLA with organo-modified MMT, particularly for the sample
      PLA-10A with fastest degradation, in comparison with pure PLA. The acceleration
      of chain scission in PLA with nanoclays was confirmed by determining the
      resultant rate constants for the hydrolytical chain scission. The critical
      molecular weight for the hydrolysis of PLA was observed to be higher than the
      critical molecular weight for onset of PLA mineralization, suggesting that PLA
      chains must be further shortened so as to be assimilated by microorganisms. In
      conclusion, MMT fillers do not represent an obstacle to acceptance of the
      investigated materials in composting facilities. 

PMID- 25981156
TI  - Conversion of tomato-peel waste into solid fuel by hydrothermal carbonization:
      Influence of the processing variables.
AB  - In this work, the influence of the variables temperature, residence time, and
      biomass/water ratio on the hydrothermal carbonization (HTC) of tomato peel was
      investigated. The implementation of a Design of Experiments - Response Surface
      Methodology approach allowed to identify the importance of each variable, as well
      as their interactions, in both the reactivity (solid yield) and energy
      densification (increase in higher heating value). The HTC residence time and
      specially temperature had a major effect on the process, increasing the solid
      yield and promoting energy densification. Ratio had a minor effect although under
      certain temperature and time conditions, it was a decisive parameter. Solid
      yields in the range 27.6% and 87.7% with corresponding high heating values 23.6
      34.6 MJ kg(-1) were obtained. From the statistical processing of the experimental
      data obtained pseudo-second order models were developed. It was proven that these
      approaches envisaged the hydrochar final characteristics successfully. From the
      elemental analysis and the FTIR spectra, it was possible to investigate the HTC
      pathway, which was defined as a combination of several processes; considering
      dehydration and decarboxylation reactions and especially lignin depolimerization
      reactions, which lead to the formation of monomeric radicals. Moreover, the
      surface morphology of selected hydrochars by Scanning Electron Microscopy (SEM)
      showed the original structure scaffold, with minor changes between hydrochars
      prepared under different conditions.

PMID- 25981158
TI  - A Meta-analysis of the Cortical Silent Period in Epilepsies.
AB  - OBJECTIVE: The cortical silent period (CSP) following transcranial magnetic
      stimulation reflects GABAB-mediated inhibition in the primary motor cortex (M1)
      and could contribute to understand the pathophysiological substrates of epileptic
      conditions. Increased CSP duration has been reported in idiopathic generalized
      epilepsy (IGE) and in partial epilepsy (PE) involving the M1, although other
      studies yielded discordant findings. We used meta-analysis to systematically
      assess the consistency of CSP changes in untreated patients with epilepsies.
      METHODS: Databases were searched for controlled studies evaluating the CSP in
      drug-naive or drug-free patients with IGE or PE. For each study, the mean
      difference with 95% confidence intervals (CIs) between CSP duration obtained in
      patients and controls was calculated. The effect of motor threshold (MT) on the
      CSP duration has also been explored by meta-analysis and meta-regression.
      RESULTS: Fourteen studies (267 patients and 234 controls) were included. A
      significant mean difference (14.16 ms, 95% CI, 1.20, 27.11 ms) was found, with
      longer CSP in patients than in controls. The mean difference was still greater
      (18.05 ms) if only the 202 IGE patients were analyzed. No MT difference emerged
      between patients and controls. Meta-regression showed no relationship between MT
      and CSP duration. CONCLUSION: Meta-analysis confirms CSP modifications in
      epilepsies, with enhancement of this cortical inhibitory measure at least in most
      IGE patients. This provides rationale for further investigations aiming to verify
      the hypotheses that increased CSP reflects compensatory neural phenomena
      counteracting transition from the interictal to ictal state and that CSP
      variability reflects the pathophysiological heterogeneity of epileptic syndromes.

PMID- 25981157
TI  - Dynamic karyotype evolution and unique sex determination systems in Leptidea wood
      white butterflies.
AB  - BACKGROUND: Chromosomal rearrangements have the potential to limit the rate and
      pattern of gene flow within and between species and thus play a direct role in
      promoting and maintaining speciation. Wood white butterflies of the genus
      Leptidea are excellent models to study the role of chromosome rearrangements in
      speciation because they show karyotype variability not only among but also within
      species. In this work, we investigated genome architecture of three cryptic
      Leptidea species (L. juvernica, L. sinapis and L. reali) by standard and
      molecular cytogenetic techniques in order to reveal causes of the karyotype
      variability. RESULTS: Chromosome numbers ranged from 2n = 85 to 91 in L.
      juvernica and 2n = 69 to 73 in L. sinapis (both from Czech populations) to 2n =
      51 to 55 in L. reali (Spanish population). We observed significant differences in
      chromosome numbers and localization of cytogenetic markers (rDNA and H3 histone
      genes) within the offspring of individual females. Using FISH with the (TTAGG) n
      telomeric probe we also documented the presence of multiple chromosome fusions
      and/or fissions and other complex rearrangements. Thus, the intraspecific
      karyotype variability is likely due to irregular chromosome segregation of
      multivalent meiotic configurations. The analysis of female meiotic chromosomes by
      GISH and CGH revealed multiple sex chromosomes: W1W2W3Z1Z2Z3Z4 in L. juvernica,
      W1W2W3Z1Z2Z3 in L. sinapis and W1W2W3W4Z1Z2Z3Z4 in L. reali. CONCLUSIONS: Our
      results suggest a dynamic karyotype evolution and point to the role of
      chromosomal rearrangements in the speciation of Leptidea butterflies. Moreover,
      our study revealed a curious sex determination system with 3-4 W and 3-4 Z
      chromosomes, which is unique in the Lepidoptera and which could also have played
      a role in the speciation process of the three Leptidea species.

PMID- 25981159
TI  - Neurochemical Modulation in Posteromedial Default-mode Network Cortex Induced by
      Transcranial Magnetic Stimulation.
AB  - BACKGROUND: The Default Mode Network (DMN) is severely compromised in several
      psychiatric and neurodegenerative disorders where plasticity alterations are
      observed. Glutamate and GABA are the major excitatory and inhibitory brain
      neurotransmitters respectively and are strongly related to plasticity responses
      and large-scale network expression. OBJECTIVE: To investigate whether regional
      Glx (Glutamate + Glutamine) and GABA could be modulated within the DMN after
      experimentally-controlled induction of plasticity and to study the effect of
      intrinsic connectivity over brain responses to stimulation. METHODS: We applied
      individually-guided neuronavigated Theta Burst Stimulation (TBS) to the left
      inferior parietal lobe (IPL) in-between two magnetic resonance spectroscopy (MRS)
      acquisitions to 36 young subjects. A resting-state fMRI sequence was also
      acquired before stimulation. RESULTS: After intermittent TBS, distal GABA
      increases in posteromedial DMN areas were observed. Instead, no significant
      changes were detected locally, in left IPL areas. Neurotransmitter modulation in
      posteromedial areas was related to baseline fMRI connectivity between this region
      and the TBS-targeted area. CONCLUSIONS: The prediction of neurotransmitter
      modulation by connectivity highlights the relevance of connectivity patterns to
      understand brain responses to plasticity-inducing protocols. The ability to
      modulate GABA in a key core of the DMN by means of TBS may open new avenues to
      evaluate plasticity mechanisms in a key area for major neurodegenerative and
      psychiatric conditions.

PMID- 25981160
TI  - 4-Hz Transcranial Alternating Current Stimulation Phase Modulates Hearing.
AB  - BACKGROUND: Non-invasive brain stimulation with transcranial alternating currents
      (tACS) has been shown to entrain slow cortical oscillations and thereby influence
      various aspects of visual perception. Much less is known about its potential
      effects on auditory perception. OBJECTIVE: In the present study, we apply a novel
      variant that enables near-equivalent stimulation of both auditory cortices to
      investigate the causal role of the phase of 4-Hz cortical oscillations for
      auditory perception. METHODS: We measured detection performance for near
      threshold auditory stimuli (4-Hz click trains) that were presented at various
      moments during ongoing tACS (two synchronous 4-Hz alternating currents applied
      transcranially to the two cerebral hemispheres). RESULTS: We found that changes
      in the relative timing of acoustic and electric stimulation cause corresponding
      perceptual changes that oscillate predominantly at the 4-Hz frequency of the
      electric stimulation, which is consistent with previous results based on 10-Hz
      tACS. CONCLUSION: TACS at various frequencies can affect auditory perception.
      Together with converging previous results based on acoustic stimulation (rather
      than tACS), this finding implies that fundamental aspects of auditory cognition
      are mediated by the temporal coherence of sound-induced cortical activity with
      ongoing cortical oscillations at multiple time scales.

PMID- 25981162
TI  - Development and psychometric evaluation of the Interactive Test of Interpersonal
      Behavior (ITIB): a pilot study examining interpersonal deficits in chronic
      depression.
AB  - Chronic depression is assumed to be caused and maintained by interpersonal
      deficits. We describe the development and psychometric evaluation of the
      Interactive Test of Interpersonal Behavior (ITIB) that we developed for self
      assessment of these deficits. Participants with chronic depression (CD, N = 15),
      episodic depression (ED, N = 15) and healthy controls (HC, N = 15) participated
      in this pilot study. They completed the ITIB and a number of pen and paper
      questionnaires including the Lubeck Questionnaire of Preoperational Thinking
      (LQPT) and the inventory of interpersonal problems (IIP). The ITIB was highly
      acceptable for use in these participants. Internal consistency for the ITIB was
      adequate for group comparisons (Cronbach's alpha = 0.649). Item-total
      correlations indicated adequate discriminatory power of five of the six items.
      The ITIB correlated moderately with the LQPT (r = 0.524) and the IIP (r = 
      0.568). The ITIB score differed significantly between the diagnostic groups
      (ANOVA F(2,42) = 6.22, p = 0.004). It was the only measure that - albeit at a
      trend level - was associated with diagnostic group (CD vs. ED) on multinomial
      logistic regression analysis (B = 0.049 +/- 0.029; OR 1.051; p = 0.088). We found
      preliminary evidence that the ITIB is an acceptable and psychometrically adequate
      measure of interpersonal behavior that distinguishes between patients with CD and
      patients with ED. If replicated with an improved version of the test, our results
      could support the hypothesis that having interpersonal problems is a core deficit
      in patients with CD.

PMID- 25981161
TI  - Multi-atlas and label fusion approach for patient-specific MRI based skull
      estimation.
AB  - PURPOSE: MRI-based skull segmentation is a useful procedure for many imaging
      applications. This study describes a methodology for automatic segmentation of
      the complete skull from a single T1-weighted volume. METHODS: The skull is
      estimated using a multi-atlas segmentation approach. Using a whole head computed
      tomography (CT) scan database, the skull in a new MRI volume is detected by
      nonrigid image registration of the volume to every CT, and combination of the
      individual segmentations by label-fusion. We have compared Majority Voting,
      Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based
      Averaging (SBA), and the Selective and Iterative Method for Performance Level
      Estimation (SIMPLE) algorithms. RESULTS: The pipeline has been evaluated
      quantitatively using images from the Retrospective Image Registration Evaluation
      database (reaching an overlap of 72.46 +/- 6.99%), a clinical CT-MR dataset
      (maximum overlap of 78.31 +/- 6.97%), and a whole head CT-MRI pair (maximum
      overlap 78.68%). A qualitative evaluation has also been performed on MRI
      acquisition of volunteers. CONCLUSION: It is possible to automatically segment
      the complete skull from MRI data using a multi-atlas and label fusion approach.
      This will allow the creation of complete MRI-based tissue models that can be used
      in electromagnetic dosimetry applications and attenuation correction in PET/MR.

PMID- 25981163
TI  - Nodulisporipyrones A-D, new bioactive alpha-pyrone derivatives from Nodulisporium
      sp.
AB  - Four new alpha-pyrone derivatives, nodulisporipyrones A-D (1-4), were isolated
      from the extract of an endolichenic fungal strain Nodulisporium sp. (65-12-7-1)
      that was fermented with rice. The structures of 1-4 were elucidated by extensive
      spectroscopic analysis, and the absolute configurations were determined by
      modified Mosher's method and electronic circular dichroism experiments. Their
      antimicrobial activities against Staphylococcus aureus 209P, Escherichia coli
      ATCC0111, Aspergillus niger R330, and Candida albicans FIM709 were evaluated
      using a paper disk diffusion method. Nodulisporipyrones A-D (1-4) are the first
      alpha-pyrone derivatives from Nodulisporium fungi. 

PMID- 25981164
TI  - Telomere length in children environmentally exposed to low-to-moderate levels of
      lead.
AB  - Shorter relative telomere length in peripheral blood is a risk marker for some
      types of cancers and cardiovascular diseases. Several environmental hazards
      appear to shorten telomeres, and this shortening may predispose individuals to
      disease. The aim of the present cross-sectional study was to assess the effect of
      environmental exposure to lead on relative telomere length (rTL) in children. A
      cohort of 99 8-year-old children was enrolled from 2007-2010. Blood lead
      concentrations (B-Pb) were measured by graphite furnace atomic absorption
      spectrometry, and blood rTL was measured by quantitative PCR. The geometric mean
      of B-Pb was 3.28 MUg/dl (range: 0.90-14.2), and the geometric mean of rTL was
      1.08 (range: 0.49-2.09). B-Pb was significantly inversely associated with rTL in
      the children (rS = -0.25, p = 0.013; in further analyses both log-transformed
      univariate regression analysis beta = -0.13, p = 0.026, and R(2)adj 4%; and beta
      = -0.12, p = 0.056 when adjusting for mothers' smoking during pregnancy, Apgar
      score, mother's and father's ages at delivery, sex and mother's education,
      R(2)adj 12%, p = 0.011). The effect of lead remained significant in children
      without prenatal tobacco exposure (N = 87, rS = -0.24, p = 0.024; in further
      analyses, beta = -0.13, p = 0.029, and R(2)adj 4%). rTL was not affected by sex,
      the concentrations of other elements in the blood (i.e., cadmium and selenium
      concentrations), or oxidative injury parameters (total antioxidant status, 8
      hydroxydeoxyguanosine and thiobarbituric acid-reactive substances). Lead exposure
      in childhood appears to be associated with shorter telomeres, which might
      contribute to diseases, such as cardiovascular disease. The inverse association
      between blood lead level and the telomeres in children emphasizes the importance
      of further reducing lead levels in the environment.

PMID- 25981165
TI  - Osilodrostat (LCI699), a potent 11beta-hydroxylase inhibitor, administered in
      combination with the multireceptor-targeted somatostatin analog pasireotide: A 13
      week study in rats.
AB  - The somatostatin analog pasireotide and the 11beta-hydroxylase inhibitor
      osilodrostat (LCI699) reduce cortisol levels by distinct mechanisms of action.
      There exists a scientific rationale to investigate the clinical efficacy of these
      two agents in combination. This manuscript reports the results of a toxicology
      study in rats, evaluating different doses of osilodrostat and pasireotide alone
      and in combination. Sixty male and 60 female rats were randomized into single-sex
      groups to receive daily doses of pasireotide (0.3mg/kg/day, subcutaneously),
      osilodrostat (20mg/kg/day, orally), osilodrostat/pasireotide in combination (low
      dose, 1.5/0.03mg/kg/day; mid-dose, 5/0.1mg/kg/day; or high dose,
      20/0.3mg/kg/day), or vehicle for 13weeks. Mean body-weight gains from baseline to
      Week 13 were significantly lower in the pasireotide-alone and combined-treatment
      groups compared to controls, and were significantly higher in female rats
      receiving osilodrostat monotherapy. Osilodrostat and pasireotide monotherapies
      were associated with significant changes in the histology and mean weights of the
      pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone was
      associated with adrenocortical hypertrophy and hepatocellular hypertrophy. In
      combination, osilodrostat/pasireotide did not exacerbate any target organ changes
      and ameliorated the liver and adrenal gland changes observed with monotherapy.
      Cmax and AUC0-24h of osilodrostat and pasireotide increased in an approximately
      dose-proportional manner. In conclusion, the pasireotide and osilodrostat
      combination did not exacerbate changes in target organ weight or toxicity
      compared with either monotherapy, and had an acceptable safety profile; addition
      of pasireotide to the osilodrostat regimen may attenuate potential adrenal gland
      hyperactivation and hepatocellular hypertrophy, which are potential side effects
      of osilodrostat monotherapy. 

PMID- 25981166
TI  - Toxicological effects of thiomersal and ethylmercury: Inhibition of the
      thioredoxin system and NADP(+)-dependent dehydrogenases of the pentose phosphate
      pathway.
AB  - Mercury (Hg) is a strong toxicant affecting mainly the central nervous, renal,
      cardiovascular and immune systems. Thiomersal (TM) is still in use in medical
      practice as a topical antiseptic and as a preservative in multiple dose vaccines,
      routinely given to young children in some developing countries, while other forms
      of mercury such as methylmercury represent an environmental and food hazard. The
      aim of the present study was to determine the effects of thiomersal (TM) and its
      breakdown product ethylmercury (EtHg) on the thioredoxin system and NADP(+)
      dependent dehydrogenases of the pentose phosphate pathway. Results show that TM
      and EtHg inhibited the thioredoxin system enzymes in purified suspensions, being
      EtHg comparable to methylmercury (MeHg). Also, treatment of neuroblastoma and
      liver cells with TM or EtHg decreased cell viability (GI50: 1.5 to 20MUM) and
      caused a significant (p<0.05) decrease in the overall activities of thioredoxin
      (Trx) and thioredoxin reductase (TrxR) in a concentration- and time-dependent
      manner in cell lysates. Compared to control, the activities of Trx and TrxR in
      neuroblastoma cells after EtHg incubation were reduced up to 60% and 80%
      respectively, whereas in hepatoma cells the reduction was almost 100%. In
      addition, the activities of glucose-6-phosphate dehydrogenase and 6
      phosphogluconate dehydrogenase were also significantly inhibited by all
      mercurials, with inhibition intensity of Hg(2+)>MeHg~EtHg>TM (p<0.05). Cell
      incubation with sodium selenite alleviated the inhibitory effects on TrxR and
      glucose-6-phosphate dehydrogenase. Thus, the molecular mechanism of toxicity of
      TM and especially of its metabolite EtHg encompasses the blockage of the
      electrons from NADPH via the thioredoxin system. 

PMID- 25981167
TI  - Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic
      inflammation through suppression of IkappaB kinase complex.
AB  - As the importance of allergic disorders such as atopic dermatitis and allergic
      asthma, research on potential drug candidates becomes more necessary. Mast cells
      play an important role as initiators of allergic responses through the release of
      histamine; therefore, they should be the target of pharmaceutical development for
      the management of allergic inflammation. In our previous study, anti-allergic
      effect of extracts of Amomum xanthioides was demonstrated. To further investigate
      improved candidates, 1,2,4,5-tetramethoxybenzene (TMB) was isolated from methanol
      extracts of A. xanthioides. TMB dose-dependently attenuated the degranulation of
      mast cells without cytotoxicity by inhibiting calcium influx. TMB decreased the
      expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha and
      interleukin (IL)-4 at both the transcriptional and translational levels.
      Increased expression of these cytokines was caused by translocation of nuclear
      factor-kappaB into the nucleus, and it was hindered by suppressing activation of
      IkappaB kinase complex. To confirm the effect of TMB in vivo, the ovalbumin (OVA)
      induced active systemic anaphylaxis (ASA) and IgE-mediated passive cutaneous
      anaphylaxis (PCA) models were used. In the ASA model, hypothermia was decreased
      by oral administration of TMB, which attenuated serum histamine, OVA-specific
      IgE, and IL-4 levels. Increased pigmentation of Evans blue was reduced by TMB in
      a dose-dependent manner in the PCA model. Our results suggest that TMB is a
      possible therapeutic candidate for allergic inflammatory diseases that acts
      through the inhibition of mast cell degranulation and expression of pro
      inflammatory cytokines. 

PMID- 25981168
TI  - Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in
      NSCLC cells.
AB  - Despite excellent initial clinical responses of non-small cell lung cancer
      (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs), many patients eventually develop resistance. According to a
      recent report, vacuolar H+ ATPase (vATPase) is overexpressed and is associated
      with chemotherapy drug resistance in NSCLC. We investigated the combined effects
      of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the
      regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs
      (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or
      concanamycin A) enhanced synergistic cell death compared to treatments with each
      drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction
      of Bnip3 expression in an Hif-1alpha dependent manner. Knock-down of Hif-1alpha
      or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1,
      suggesting that Hif-1alpha/Bnip3 induction promoted resistance to cell death
      induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1alpha and Bnip3
      expression induced by the vATPase inhibitors, suggesting that they enhanced the
      sensitivity of the cells to these inhibitors by decreasing Hif-1alpha/Bnip3
      expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of
      NSCLC cells to vATPase inhibitors by decreasing Hif-1alpha/Bnip3 expression. We
      suggest that combined treatment with EGFR TKIs and vATPase inhibitors is
      potentially effective for the treatment of NSCLC. 

PMID- 25981169
TI  - Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non
      small cell lung cancer based on epidermal growth factor receptor mutation status.
AB  - BACKGROUND: Neoadjuvant erlotinib and customized adjuvant therapy are appealing
      but controversial. The purpose of this study was to evaluate the role of
      biomarker-guided neoadjuvant treatment strategy in patients with IIIA-N2 non
      small cell lung cancer (NSCLC) stratified by epidermal growth factor receptor
      (EGFR) mutation status. FINDINGS: Patients with resectable histologically
      documented stage IIIA-N2 NSCLC were assigned to a neoadjuvant erlotinib arm or a
      gemcitabine/carboplatin (GC) arm based on EGFR mutation status. The primary
      endpoint was response rate (RR). Secondary endpoints were progression-free
      survival (PFS) and overall survival (OS). Twenty-four patients with IIIA-N2 NSCLC
      were enrolled in the trial from January 2008 until May 2011. The overall response
      rate was 41.7% and the PFS and OS were 7.9 and 23.2 months, respectively, in
      overall population. The RR was 58.3% (7/12) for the erlotinib arm with mutant
      EGFR and 25.0% (3/12) for the GC arm with wild type EGFR (P = 0.18). Median PFS
      was 6.9 months versus 9.0 months, respectively (P = 0.071). Median OS was 14.5
      months for the erlotinib arm and 28.1 months for the GC arm (P = 0.201). No
      unexpected toxicities were observed. CONCLUSIONS: The primary endpoint was met
      and biomarker-guided neoadjuvant treatment strategy in patients with IIIA-N2
      NSCLC is feasible. Erlotinib alone in neoadjuvant setting of EGFR mutant
      population showed an improved response but without survival benefits. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00600587
      https://www.clinicaltrials.gov/ct2/show/NCT00600587?term=NCT00600587&rank=1.

PMID- 25981170
TI  - Eye Tracking Reveals Abnormal Visual Preference for Geometric Images as an Early
      Biomarker of an Autism Spectrum Disorder Subtype Associated With Increased
      Symptom Severity.
AB  - BACKGROUND: Clinically and biologically, autism spectrum disorder (ASD) is
      heterogeneous. Unusual patterns of visual preference as indexed by eye tracking
      are hallmarks; however, whether they can be used to define an early biomarker of
      ASD as a whole or leveraged to define a subtype is unclear. To begin to examine
      this issue, large cohorts are required. METHODS: A sample of 334 toddlers from
      six distinct groups (115 toddlers with ASD, 20 toddlers with ASD features, 57
      toddlers with developmental delay, 53 toddlers with other conditions [e.g.,
      premature birth, prenatal drug exposure], 64 toddlers with typical development,
      and 25 unaffected toddlers with siblings with ASD) was studied. Toddlers watched
      a movie containing geometric and social images. Fixation duration and number of
      saccades within each area of interest and validation statistics for this
      independent sample were computed. Next, to maximize power, data from our previous
      study (n = 110) were added for a total of 444 subjects. A subset of toddlers
      repeated the eye-tracking procedure. RESULTS: As in the original study, a subset
      of toddlers with ASD fixated on geometric images >69% of the time. Using this
      cutoff, sensitivity for ASD was 21%, specificity was 98%, and positive predictive
      value was 86%. Toddlers with ASD who strongly preferred geometric images had 1)
      worse cognitive, language, and social skills relative to toddlers with ASD who
      strongly preferred social images and 2) fewer saccades when viewing geometric
      images. Unaffected siblings of ASD probands did not show evidence of heightened
      preference for geometric images. Test-retest reliability was good. Examination of
      age effects suggested that this test may not be appropriate with children >4
      years old. CONCLUSIONS: Enhanced visual preference for geometric repetition may
      be an early developmental biomarker of an ASD subtype with more severe symptoms.

PMID- 25981172
TI  - Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels.
AB  - BACKGROUND: Disruption of the endocannabinoid system through pharmacological or
      genetic invalidation of cannabinoid CB1 receptors has been linked to depression
      in humans and depression-like behaviors in mice. The two main endogenous
      cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on
      demand from phospholipids. The pathways and enzymes involved in endocannabinoid
      biosynthesis thus play a major role in regulating the activity of this system.
      This study investigates the role of the main 2-AG producing enzyme diacylglycerol
      lipase alpha (DAGL-alpha). METHODS: We generated and used knockout mice lacking
      DAGL-alpha (Dagla(-/-)) to assess the behavioral consequences of reduced
      endocannabinoid levels in the brain. We performed different behavior tests to
      determine anxiety- and depression-related behavioral changes in Dagla(-/-) mice.
      We also analyzed expression of genes related to the endocannabinoid system via
      real-time polymerase chain reaction and used the mitotic marker 5-bromo-2'
      deoxyuridine to analyze adult neurogenesis. RESULTS: Dagla(-/-) animals show an
      80% reduction of brain 2-AG levels but also a reduction in cortical and amygdalar
      anandamide. The behavioral changes induced by Dagla deletion include a reduced
      exploration of the central area of the open field, a maternal neglect behavior, a
      fear extinction deficit, increased behavioral despair, increased anxiety-related
      behaviors in the light/dark box, and reduced hippocampal neurogenesis. Some of
      these behavioral changes resemble those observed in animals lacking the CB1
      receptor. CONCLUSIONS: Our findings demonstrate that the deletion of Dagla
      adversely affects the emotional state of animals and results in enhanced anxiety,
      stress, and fear responses.

PMID- 25981173
TI  - Fear Generalization and Anxiety: Behavioral and Neural Mechanisms.
AB  - Fear can be an adaptive emotion that helps defend against potential danger.
      Classical conditioning models elegantly describe how animals learn which stimuli
      in the environment signal danger, but understanding how this learning is
      generalized to other stimuli that resemble aspects of a learned threat remains a
      challenge. Critically, the overgeneralization of fear to harmless stimuli or
      situations is a burden to daily life and characteristic of posttraumatic stress
      disorder and other anxiety disorders. Here, we review emerging evidence on
      behavioral and neural mechanisms of generalization of emotional learning with the
      goal of encouraging further research on generalization in anxiety disorders. We
      begin by placing research on fear generalization in a rich historical context of
      stimulus generalization dating back to Pavlov, which lays the foundation for
      theoretical and experimental approaches used today. We then transition to
      contemporary behavioral and neurobiological research on generalization of
      emotional learning in humans and nonhuman animals and discuss the factors that
      promote generalization on the one hand from discrimination on the other hand. 

PMID- 25981171
TI  - Altered expression of CDC42 signaling pathway components in cortical layer 3
      pyramidal cells in schizophrenia.
AB  - BACKGROUND: Cognitive dysfunction in schizophrenia is associated with a lower
      density of dendritic spines on deep layer 3 pyramidal cells in the dorsolateral
      prefrontal cortex (DLPFC). These alterations appear to reflect dysregulation of
      the actin cytoskeleton required for spine formation and maintenance. Consistent
      with this idea, altered expression of genes in the cell division cycle 42 (CDC42)
      CDC42 effector protein (CDC42EP) signaling pathway, a key organizer of the actin
      cytoskeleton, was previously reported in DLPFC gray matter from subjects with
      schizophrenia. We examined the integrity of the CDC42-p21-activated
      serine/threonine protein kinases (PAK)-LIM domain-containing serine/threonine
      protein kinases (LIMK) signaling pathway in schizophrenia in a layer-specific and
      cell type-specific fashion in DLPFC deep layer 3. METHODS: Using laser
      microdissection, samples of DLPFC deep layer 3 were collected from 56 matched
      pairs of subjects with schizophrenia and comparison subjects, and levels of CDC42
      PAK-LIMK pathway messenger RNAs were measured by quantitative polymerase chain
      reaction. These same transcripts also were quantified by microarray in samples of
      individually microdissected deep layer 3 pyramidal cells from a subset of the
      same subjects and from monkeys exposed to antipsychotics. RESULTS: Relative to
      comparison subjects, CDC42EP4, LIMK1, LIMK2, ARHGDIA, and PAK3 messenger RNA
      levels were significantly upregulated in subjects with schizophrenia in laminar
      and cellular samples. In contrast, CDC42 and PAK1 messenger RNA levels were
      significantly downregulated specifically in deep layer 3 pyramidal cells. These
      differences were not attributable to psychotropic medications or other comorbid
      factors. CONCLUSIONS: Findings from the present and prior studies converge on
      synergistic alterations in CDC42 signaling pathway that could destabilize actin
      dynamics and produce spine deficits preferentially in deep layer 3 pyramidal
      cells in schizophrenia.

PMID- 25981174
TI  - Of Mice, Men, and Microbial Opsins: How Optogenetics Can Help Hone Mouse Models
      of Mental Illness.
AB  - Genetic, pharmacologic, and behavioral manipulations have long been powerful
      tools for generating rodent models to study the neural substrates underlying
      psychiatric disease. Recent advances in the use of optogenetics in awake behaving
      rodents has added an additional valuable methodology to this experimental
      toolkit. Here, we review several recent studies that leverage optogenetic
      technologies to elucidate neural mechanisms possibly related to depression,
      anxiety, and obsessive-compulsive disorder. We use a few illustrative examples to
      highlight key emergent principles about how optogenetics, in conjunction with
      more established modalities, can help to organize our understanding of how
      disease-related states, specific neuronal circuits, and various behavioral assays
      fit into hierarchical frameworks such as the National Institute of Mental Health
      Research Domain Criteria matrix.

PMID- 25981175
TI  - Neonatal Treatment with a Pegylated Leptin Antagonist Induces Sexually Dimorphic
      Effects on Neurones and Glial Cells, and on Markers of Synaptic Plasticity in the
      Developing Rat Hippocampal Formation.
AB  - The present study aimed to better understand the role of the neonatal leptin
      surge, which peaks on postnatal day (PND)9-10, on the development of the
      hippocampal formation. Accordingly, male and female rats were administered with a
      pegylated leptin antagonist on PND9 and the expression of neurones, glial cells
      and diverse markers of synaptic plasticity was then analysed by
      immunohistochemistry in the hippocampal formation. Antagonism of the actions of
      leptin at this specific postnatal stage altered the number of glial fibrillary
      acidic protein positive cells, and also affected type 1 cannabinoid receptors,
      synaptophysin and brain-derived neurotrophic factor (BDNF), with the latter
      effect being sexually dimorphic. The results indicate that the physiological
      leptin surge occurring around PND 9-10 is critical for hippocampal formation
      development and that the dynamics of leptin activity might be different in males
      and females. The data obtained also suggest that some but not all the previously
      reported effects of maternal deprivation on hippocampal formation development
      (which markedly reduces leptin levels at PND 9-10) might be mediated by leptin
      deficiency in these animals. 

PMID- 25981176
TI  - Confining Iron Carbide Nanocrystals inside CNx@CNT toward an Efficient
      Electrocatalyst for Oxygen Reduction Reaction.
AB  - The development of low-cost electrocatalysts with comparable activity for oxygen
      reduction reaction (ORR) to substitute platinum-based catalysts is imperative but
      still challenging for the commercialization of fuel cells. Herein, we reported a
      strategy to effectively confine iron carbide nanocrystals in N-doped carbon
      coated on carbon nanotubes (CNx@CNT), which prevented the agglomeration of iron
      carbide during pyrolysis and thus provided the sufficient highly active catalytic
      sites. Together with the benefit from three-dimensional conductive network of CNT
      based core-shell structure for fast electron transfer and rapid mass transfer,
      the developed nanocatalyst exhibited the significantly enhanced electrocatalytic
      activity for ORR, as well as high durability and methanol tolerance. Moreover, it
      was interestingly found that the types of the confined iron compounds appreciably
      affected the performance of the catalysts, and Fe3C might be most effective on
      improving ORR activity in this case. 

PMID- 25981177
TI  - Ganglioside contained in the neuronal tissue-enriched acidic protein of 22 kDa
      (NAP-22) fraction prepared from the detergent-resistant membrane microdomain of
      rat brain inhibits the phosphatase activity of calcineurin.
AB  - Neurons have well-developed membrane microdomains called "rafts" that are
      recovered as a detergent-resistant membrane microdomain fraction (DRM). Neuronal
      tissue-enriched acidic protein of 22 kDa (NAP-22) is one of the major protein
      components of neuronal DRM. To determine the cellular function of NAP-22,
      interacting proteins were screened with an immunoprecipitation assay, and
      calcineurin (CaN) was detected. Further studies with NAP-22 prepared from DRM and
      CaN expressed in bacteria showed the binding of these proteins and a dose
      dependent inhibitory effect of the NAP-22 fraction on the phosphatase activity of
      CaN. On the other hand, NAP-22 expressed in bacteria showed low binding to CaN
      and a weak inhibitory effect on phosphatase activity. To solve this discrepancy,
      identification of a nonprotein component that modulates CaN activity in the DRM
      derived NAP-22 fraction was attempted. After lyophilization, a lipid fraction was
      extracted with chloroform/methanol. The lipid fraction showed an inhibitory
      effect on CaN without NAP-22, and further fractionation of the extract with thin
      layer chromatography showed the presence of several lipid bands having an
      inhibitory effect on CaN. The mobility of these bands coincided with that of
      authentic ganglioside (GM1a, GD1a, GD1b, and GT1b), and authentic ganglioside
      showed an inhibitory effect on CaN. Treatment of lipid with endoglycoceramidase,
      which degrades ganglioside to glycochain and ceramide, caused a diminution of the
      inhibitory effect. These results show that DRM-derived NAP-22 binds several
      lipids, including ganglioside, and that ganglioside inhibits the phosphatase
      activity of CaN.

PMID- 25981178
TI  - Clozapine use and sedentary lifestyle as determinants of metabolic syndrome in
      outpatients with schizophrenia.
AB  - BACKGROUND: Schizophrenia patients are in danger of developing metabolic syndrome
      (MetS) and its outcomes type 2 diabetes and cardiovascular disease. Antipsychotic
      treatment and adverse lifestyle increase the burden of metabolic problems in
      schizophrenia, but little is known about the role of patients' current
      psychiatric problems and living arrangements in MetS. AIMS: This study aims to
      evaluate correlations between MetS, severity of psychiatric symptoms, living
      arrangements, health behaviour and antipsychotic medication in outpatients with
      schizophrenia spectrum disorders. METHODS: A general practitioner and psychiatric
      nurses performed a comprehensive health examination for all consenting patients
      with schizophrenia spectrum disorders treated in a psychosis outpatient clinic.
      Examination comprised of an interview, a questionnaire, measurements, laboratory
      tests and a general clinical examination. Diagnosis of MetS was made according to
      International Diabetes Federation (IDF) definition. Correlations were calculated
      and logistic regression analysis performed with SAS. RESULTS: 276 patients (men n
      = 152, mean age +/- standard deviation = 44.9 +/- 12.6 years) participated in the
      study; 58.7% (n = 162) of them had MetS according to the IDF definition.
      Clozapine use doubled the risk of MetS (OR = 2.04, 95% CI 1.09-3.82, P = 0.03),
      whereas self-reported regular physical activity decreased the risk significantly
      (OR = 0.32, 95% CI 0.18-0.57, P < 0.001). We found no correlations between MetS
      and living arrangements or current severity of psychiatric symptoms. CONCLUSIONS:
      MetS was alarmingly common in our sample. Even moderate physical activity was
      associated with decreased risk of MetS. Promotion of a physically active
      lifestyle should be one of the targets in treatment of schizophrenia, especially
      in patients using clozapine.

PMID- 25981179
TI  - The Effects of Parental Health Shocks on Adult Offspring Smoking Behavior and
      Self-Assessed Health.
AB  - An important avenue for smoking deterrence may be through familial ties if adult
      smokers respond to parental health shocks. In this paper, we merge the Original
      Cohort and the Offspring Cohort of the Framingham Heart Study to study how adult
      offspring smoking behavior and subjective health assessments vary with elder
      parent smoking behavior and health outcomes. These data allow us to model the
      smoking behavior of adult offspring over a 30-year period contemporaneously with
      parental behaviors and outcomes. We find strong 'like father, like son' and 'like
      mother, like daughter' correlations in smoking behavior. We find that adult
      offspring significantly curtail their own smoking following an own health shock;
      however, we find limited evidence that offspring smoking behavior is sensitive to
      parent health, with the notable exception that women significantly reduce both
      their smoking participation and intensity following a smoking-related
      cardiovascular event of a parent. We also model the subjective health assessment
      of adult offspring as a function of parent health, and we find that women report
      significantly worse health following the smoking-related death of a parent.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25981180
TI  - Rethinking Indian monsoon rainfall prediction in the context of recent global
      warming.
AB  - Prediction of Indian summer monsoon rainfall (ISMR) is at the heart of tropical
      climate prediction. Despite enormous progress having been made in predicting ISMR
      since 1886, the operational forecasts during recent decades (1989-2012) have
      little skill. Here we show, with both dynamical and physical-empirical models,
      that this recent failure is largely due to the models' inability to capture new
      predictability sources emerging during recent global warming, that is, the
      development of the central-Pacific El Nino-Southern Oscillation (CP-ENSO), the
      rapid deepening of the Asian Low and the strengthening of North and South Pacific
      Highs during boreal spring. A physical-empirical model that captures these new
      predictors can produce an independent forecast skill of 0.51 for 1989-2012 and a
      92-year retrospective forecast skill of 0.64 for 1921-2012. The recent low skills
      of the dynamical models are attributed to deficiencies in capturing the
      developing CP-ENSO and anomalous Asian Low. The results reveal a considerable gap
      between ISMR prediction skill and predictability. 

PMID- 25981181
TI  - Implementation of concussion guidelines in community Australian Football and
      Rugby League-The experiences and challenges faced by coaches and sports trainers.
AB  - OBJECTIVES: While guidelines outlining the appropriate management of sport
      related concussion have been developed and adapted for use within community
      sport, it remains unknown how they are experienced by those responsible for
      implementing them. DESIGN: Longitudinal study. METHODS: 111 coaches and sports
      trainers from community-level Australian Football and Rugby League teams
      completed pre- and post-season surveys assessing their attitudes towards using
      concussion guidelines. Participants also provided post-season feedback regarding
      their experiences in using the guidelines. RESULTS: 71% of participants reported
      using the guidelines in the preceding season. Post-season attitude was related to
      pre-season attitude (p=0.002), football code (p=0.015), and team role (p=0.045).
      An interaction between team role and guideline use (p=0.012) was also found, with
      coaches who had used the guidelines, and sports trainers who had not, reporting
      more positive post-season attitudes towards using the concussion guidelines.
      Implementation challenges included disputing of decisions about return-to-play by
      players, parents, and coaches, and a perceived lack of time. Recommendations for
      improved guideline materials included using larger fonts and providing for
      witnessing of advice given to players. CONCLUSIONS: This is the first study to
      examine the implementation of concussion guidelines in community sport. Training
      of coaches/sports trainers needs enhancement. In addition, new education should
      be developed for parents/players about the importance of the return-to-play
      advice given to them by those who follow these guidelines. Information provided
      by those who attempted to use the guidelines will assist the refinement of
      implementation and dissemination processes around concussion guidelines across
      sports.

PMID- 25981182
TI  - Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent
      clinical efficacy.
AB  - Recent progress in tumor immunology has revealed that tumors generate
      immunologically restrained milieu during the process of their growth, which
      facilitates the escape of tumors from host immune systems. Immune checkpoint
      molecules, which transduce co-inhibitory signals to immuno-competent cells, are
      one of the most important components conferring the immunosuppressive capacity in
      the tumor microenvironment. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
      and programmed cell death-1 (PD-1) are typical immune checkpoint molecules
      intimately involved in the suppression of anti-tumor immunity. Antibodies against
      those molecules have been developed, such as ipilimumab (anti-CTLA-4 antibody),
      nivolumab and pembrolizumab (anti-PD-1 antibody), and have been approved by
      regulatory agencies and used in some countries. Treatment with these antibodies
      demonstrates previously unobserved clinical efficacies superior to the
      conventional therapies. In this review, we first discuss the escape mechanisms of
      cancer from host immune systems, and then focus on the recent advances in immune
      checkpoint blockade therapy and on the new findings of related immune reactions,
      aiming to provide a better understanding of the novel cancer immunotherapies. 

PMID- 25981183
TI  - Early specialist care for diabetes: who benefits most? A propensity score-matched
      cohort study.
AB  - AIMS: To examine whether early endocrinologist care reduces the risk of
      cardiovascular complications among newly diagnosed patients with diabetes of
      differing complexity. METHODS: We conducted a population-based propensity score
      matched cohort study using provincial health data from Ontario, Canada. Adults
      (>= 30 years) diagnosed with diabetes between 1 April 1998 and 31 March 2006 who
      received endocrinologist care in the first year of diagnosis were matched to a
      comparison group receiving primary care alone (N = 79 020) based on propensity
      scores and medical complexity (assigned using information on chronic conditions).
      Individuals were followed for 3- and 5-year outcomes, including non-fatal acute
      myocardial infarction or coronary heart disease death (primary endpoint), major
      cardiovascular events (acute myocardial infarction, stroke) or all-cause death,
      amputation and end-stage renal disease. RESULTS: Among medically complex
      patients, early endocrinologist care was associated with a lower 3-year incidence
      of the primary endpoint (hazard ratio 0.89, 95% CI 0.78-1.01) and major
      cardiovascular events or all-cause death (hazard ratio 0.91, 95% CI 0.85-0.97).
      These effects persisted after accounting for a higher incidence of end-stage
      renal disease on follow-up and were greatest in those with >= 3 visits to an
      endocrinologist (primary endpoint: hazard ratio 0.69, 95% CI 0.56-0.86 and 0.61,
      95% CI 0.45-0.82, for unadjusted and end-stage renal disease adjusted analyses,
      respectively). In contrast, no benefit was observed in the non-medically complex
      subgroup. Overall effects were similar at 5 years. CONCLUSIONS: Early
      endocrinologist care is associated with a lower incidence of cardiovascular
      events and death among newly diagnosed patients with diabetes who have comorbid
      medical conditions.

PMID- 25981184
TI  - Synthesis and use of universal sequence probes in fluorogenic multi-strand
      hybridisation complexes for economical nucleic acid testing.
AB  - Analysis of nucleic acid amplification products has become the gold standard for
      applications such as pathogen detection and characterisation of single nucleotide
      polymorphisms and short tandem repeat sequences. The development of real-time PCR
      and melting curve analysis using fluorescent probes has simplified nucleic acid
      analyses. However, the cost of probe synthesis can be prohibitive when developing
      large panels of tests. We describe an economic two-stage method for probe
      synthesis, and a new method for nucleic acid sequence analysis which together
      considerably reduce costs. The analysis method utilises three-strand and four
      strand hybridisation complexes for the detection and identification of nucleic
      acid target sequences by real-time PCR and fluorescence melting. 

PMID- 25981185
TI  - The effect of red, green and blue lasers on healing of oral wounds in diabetic
      rats.
AB  - BACKGROUND AND OBJECTIVE: Many studies have demonstrated that low-level laser
      therapy (LLLT) can improve wound healing in non-diabetic and diabetic animals. We
      compared the effects of red, green, and blue lasers in terms of accelerating oral
      wound healing in diabetic rats. MATERIAL AND METHODS: Diabetes was successfully
      induced in 32 male Wistar rats using intraperitoneal injection of Streptozotocin
      (150 mg/kg). After intraperitoneal injection of the anesthetic agent, a full
      thickness oral wound (10 mm * 2 mm) was created aseptically with a scalpel on
      hard palate of the diabetic rats. The study was performed using red (630 nm),
      green (532 nm), and blue (425 nm) lasers and a control group. We used an energy
      density of 2J/cm2 and a treatment schedule of 3 times/week for 10 days. The area
      of wounds was measured and recorded on a chart for all rats. On the 10th day, the
      samples were then sacrificed and a full-thickness sample of wound area was
      prepared for pathological study. RESULTS: We observed a significant difference
      (p<0.001) in the mean slope values of wound healing between treatment and control
      groups. Moreover, the mean slope of wound healing differed significantly between
      red laser and two other lasers - blue and green (p<0.001). The mean slopes of
      wound healing were not significantly different between blue laser and green laser
      (p=0.777). CONCLUSION: The results of the present study provide evidence that
      wound healing is slower in control rats compared to the treatment groups.
      Moreover, the findings suggest that wound healing occurs faster with red laser
      compared to blue and green lasers.

PMID- 25981186
TI  - Dosimeter based on 8-methoxypsoralen for UVA exposures over extended periods.
AB  - A miniaturized UVA dosimeter based on 8-methoxypsoralen (8-MOP) has been
      developed and characterized for the evaluation of UVA (320-400 nm) exposures over
      extended periods longer than one day. Current research indicates that UVA is a
      contributing factor in non-melanoma skin cancers and the associated financial
      cost of damage caused by UVA is significant. Dosimetry is a technique that is
      commonly employed to measure UV exposures to an object or subject. Miniaturized
      dosimeters using polyphenylene oxide (PPO) have previously been used to measure
      received erythemal UV (UVery) exposures. A new miniaturized dosimeter using 8-MOP
      as the photoactive material has been characterized and a technique developed for
      the calibration of UVA exposures. Using Mylar as a UVB filter the spectral
      response showed 8-MOP to react only to wavelengths between 320 and 400 nm. The
      measured cosine response has an error of less than 13.8% for angles between 0
      degrees  and 60 degrees . Seasonal dose response tests conducted, indicate that
      these UVA dosimeters are able to measure exposures <4.6 kJ/m(2). These results
      have shown that a dosimeter constructed from 8-MOP in conjunction with a Mylar
      filter can measure UVA exposures over extended periods longer than one day.

PMID- 25981187
TI  - V-shaped ligand 1,3-bis(1-ethylbenzimidazol-2-yl)-2-thiapropane and
      manganese(II), cobalt(II) and copper(II) complexes: Synthesis, crystal structure,
      DNA-binding properties and antioxidant activities.
AB  - A V-shaped ligand 1,3-bis(1-ethylbenzimidazol-2-yl)-2-thiapropane (bebt) and its
      transition metal complexes, [Mn(bebt)(pic)2].CH3OH (pic=picrate) 1,
      [Co(bebt)2](pic)22 and [Cu(bebt)2](pic)2.2DMF 3, have been synthesized and
      characterized. The coordinate forms of complexes 1 and 2 are basically alike,
      which can be described as six-coordinated distorted octahedron. The geometric
      structure around Cu(II) atom can be described as distorted tetrahedral in complex
      3. The DNA-binding properties of the ligand bebt and complexes have been
      investigated by electronic absorption, fluorescence, and viscosity measurements.
      The results suggest that bebt and complexes bind to DNA via an intercalative
      binding mode and the order of the binding affinity is 1<2<3<bebt. The possible
      relations between the structure and DNA-binding properties are also discussed.
      Moreover, the complex 3 possess significant antioxidant activity against
      superoxide and hydroxyl radicals, and the scavenging effects of it are stronger
      than standard mannitol and vitamin C. 

PMID- 25981188
TI  - B blood group: A strong risk factor for venous thromboembolism recurrence.
AB  - BACKGROUND: Non-O blood group patients are at higher risk of first episode of
      venous thromboembolism (VTE). However, only little is known about the risk of
      recurrence according to the blood group. In this study, we aimed to determine the
      impact of ABO blood group on VTE recurrence. METHODS: We prospectively recruited
      106 consecutive patients with a first documented episode of pulmonary embolism
      (PE). Patients were followed at least 12months after anticoagulation
      discontinuation. The main endpoint was recurrence of symptomatic VTE. RESULTS:
      Data from 100 patients were analyzed. Median follow-up was 28months [24-34.8]. PE
      was unprovoked in 48 patients. Mean anticoagulation duration was 5.3+/-2.2months.
      The rate of VTE recurrence was 12.7 per 100 patient-years (30 recurrences). B
      blood group patients had a 2.7-fold increased risk of VTE recurrence (95%CI 1.1
      6.2, p=0.03). On multivariate analysis, B blood group was the strongest
      independent predictor of VTE recurrence (Hazard Ratio (HR) 2.6, 95%CI 1.1-6.1,
      p=0.04). In contrast, A and AB blood groups were not associated with VTE
      recurrence. VTE recurrences were less frequent in O blood group compared to non-O
      patients (HR 0.5, 95%CI 0.2-1.1, p=0.09). O blood group women had a 5-fold
      decreased risk of VTE recurrence (HR 0.2, 95%CI 0.1-0.8, p=0.01). CONCLUSIONS:
      Non-O blood groups, beyond being involved in the occurrence of a first VTE event,
      also contribute to VTE recurrence. B blood group is strongly associated with VTE
      recurrence, thus high-risk B blood group patients could benefit from long-term
      anticoagulation therapy after a first VTE event.

PMID- 25981189
TI  - Variance estimation for nucleotide substitution models.
AB  - The current variance estimators for most evolutionary models were derived when a
      nucleotide substitution number estimator was approximated with a simple first
      order Taylor expansion. In this study, we derive three variance estimators for
      the F81, F84, HKY85 and TN93 nucleotide substitution models, respectively. They
      are obtained using the second order Taylor expansion of the substitution number
      estimator, the first order Taylor expansion of a squared deviation and the second
      order Taylor expansion of a squared deviation, respectively. These variance
      estimators are compared with the existing variance estimator in terms of a
      simulation study. It shows that the variance estimator, which is derived using
      the second order Taylor expansion of a squared deviation, is more accurate than
      the other three estimators. In addition, we also compare these estimators with an
      estimator derived by the bootstrap method. The simulation shows that the
      performance of this bootstrap estimator is similar to the estimator derived by
      the second order Taylor expansion of a squared deviation. Since the latter one
      has an explicit form, it is more efficient than the bootstrap estimator. 

PMID- 25981190
TI  - An Effect of Oak-Wood Extract (Robuvit(r)) on Energy State of Healthy Adults-A
      Pilot Study.
AB  - The purpose of our study was to examine the psychological benefits of the
      treatment with Robuvit(r) (Horphag Research Ltd.) - polyphenolic extract obtained
      from the wood of oak Quercus robur - on the healthy elderly individuals using
      energy subscale scores of the Activation - Deactivation Adjective Check List.
      Analysis was focused on the comparison of pre-post treatment effect of Robuvit on
      symptoms of fatigue. In the total group of volunteers, significant increase of
      average question scores was found in three of four subscales of feelings (energy,
      tiredness, and tension) after 4 weeks of Robuvit administration. Effects of
      extract were observed mainly after stratification of total group of volunteers
      according to the level of feeling at the pre-treatment questionnaire. Our results
      demonstrate positive effect of Robuvit on mental and energy level in healthy
      human without any unwanted side effects.

PMID- 25981191
TI  - Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme.
AB  - BACKGROUND: The most prevalent phenotype of asthma is characterized by eosinophil
      dominated inflammation that is driven by a type 2 helper T cell (Th2).
      Therapeutic targeting of GATA3, an important transcription factor of the Th2
      pathway, may be beneficial. We evaluated the safety and efficacy of SB010, a
      novel DNA enzyme (DNAzyme) that is able to cleave and inactivate GATA3 messenger
      RNA (mRNA). METHODS: We conducted a randomized, double-blind, placebo-controlled,
      multicenter clinical trial of SB010 involving patients who had allergic asthma
      with sputum eosinophilia and who also had biphasic early and late asthmatic
      responses after laboratory-based allergen provocation. A total of 40 patients
      could be evaluated; 21 were assigned to receive 10 mg of SB010, and 19 were
      assigned to receive placebo, with each study drug administered by means of
      inhalation once daily for 28 days. An allergen challenge was performed before and
      after the 28-day period. The primary end point was the late asthmatic response as
      quantified by the change in the area under the curve (AUC) for forced expiratory
      volume in 1 second (FEV1). RESULTS: After 28 days, SB010 attenuated the mean late
      asthmatic response by 34%, as compared with the baseline response, according to
      the AUC for FEV1, whereas placebo was associated with a 1% increase in the AUC
      for FEV1 (P=0.02). The early asthmatic response with SB010 was attenuated by 11%
      as measured by the AUC for FEV1, whereas the early response with placebo was
      increased by 10% (P=0.03). Inhibition of the late asthmatic response by SB010 was
      associated with attenuation of allergen-induced sputum eosinophilia and with
      lower levels of tryptase in sputum and lower plasma levels of interleukin-5.
      Allergen-induced levels of fractional exhaled nitric oxide and airway
      hyperresponsiveness to methacholine were not affected by either SB010 or placebo.
      CONCLUSIONS: Treatment with SB010 significantly attenuated both late and early
      asthmatic responses after allergen provocation in patients with allergic asthma.
      Biomarker analysis showed an attenuation of Th2-regulated inflammatory responses.
      (Funded by Sterna Biologicals and the German Federal Ministry of Education and
      Research; ClinicalTrials.gov number, NCT01743768.).

PMID- 25981192
TI  - Toward equality of biodiversity knowledge through technology transfer.
AB  - To help stem the continuing decline of biodiversity, effective transfer of
      technology from resource-rich to biodiversity-rich countries is required.
      Biodiversity technology as defined by the Convention on Biological Diversity
      (CBD) is a complex term, encompassing a wide variety of activities and interest
      groups. As yet, there is no robust framework by which to monitor the extent to
      which technology transfer might benefit biodiversity. We devised a definition of
      biodiversity technology and a framework for the monitoring of technology transfer
      between CBD signatories. Biodiversity technology within the scope of the CBD
      encompasses hard and soft technologies that are relevant to the conservation and
      sustainable use of biodiversity, or make use of genetic resources, and that
      relate to all aspects of the CBD, with a particular focus on technology transfer
      from resource-rich to biodiversity-rich countries. Our proposed framework
      introduces technology transfer as a response indicator: technology transfer is
      increased to stem pressures on biodiversity. We suggest an initial approach of
      tracking technology flow between countries; charting this flow is likely to be a
      one-to-many relationship (i.e., the flow of a specific technology from one
      country to multiple countries). Future developments should then focus on
      integrating biodiversity technology transfer into the current pressure-state
      response indicator framework favored by the CBD (i.e., measuring the influence of
      technology transfer on changes in state and pressure variables). Structured
      national reporting is important to obtaining metrics relevant to technology and
      knowledge transfer. Interim measures, that can be used to assess biodiversity
      technology or knowledge status while more in-depth indicators are being
      developed, include the number of species inventories, threatened species lists,
      or national red lists; databases on publications and project funding may provide
      measures of international cooperation. Such a pragmatic approach, followed by
      rigorous testing of specific technology transfer metrics submitted by CBD
      signatories in a standardized manner may in turn improve the focus of future
      targets on technology transfer for biodiversity conservation. 

PMID- 25981193
TI  - The Use of Transporter Probe Drug Cocktails for the Assessment of Transporter
      Based Drug-Drug Interactions in a Clinical Setting-Proposal of a Four Component
      Transporter Cocktail.
AB  - Probe drug cocktails are used clinically to assess the potential for drug-drug
      interactions (DDIs), and in particular, DDIs resulting from coadministration of
      substrates and inhibitors of cytochrome P450 enzymes. However, a probe drug
      cocktail has not been identified to assess DDIs involving inhibition of drug
      transporters. We propose a cocktail consisting of the following substrates to
      explore the potential for DDIs caused by inhibition of key transporters: digoxin
      (P-glycoprotein, P-gp), rosuvastatin (breast cancer resistance protein, BCRP;
      organic anion transporting polypeptides, OATP), metformin (organic cation
      transporter, OCT; multidrug and toxin extrusion transporters, MATE), and
      furosemide (organic anion transporter, OAT). Furosemide was evaluated in vitro,
      and is a substrate of OAT1 and OAT3, with Km values of 38.9 and 21.5 MUM,
      respectively. Furosemide was also identified as a substrate of BCRP, OATP1B1, and
      OATP1B3. Furosemide inhibited BCRP (50% inhibition of drug transport: 170 MUM),
      but did not inhibit OATP1B1, OATP1B3, OCT2, MATE1, and MATE2-K at concentrations
      below 300 MUM, and P-gp at concentrations below 2000 MUM. Conservative approaches
      for the estimation of the likelihood of in vivo DDIs indicate a remote chance of
      in vivo transporter inhibition by these probe drugs when administered at low
      single oral doses. This four component probe drug cocktail is therefore proposed
      for clinical evaluation.

PMID- 25981194
TI  - Student performance on practical gross anatomy examinations is not affected by
      assessment modality.
AB  - Anatomical education is becoming modernized, not only in its teaching and
      learning, but also in its assessment formats. Traditional "steeplechase"
      examinations are being replaced with online gross anatomy examinations. The aims
      of this study were to: (1) determine if online anatomy practical examinations are
      equivalent to traditional anatomy practical examinations; and (2) to examine if
      students' perceptions of the online or laboratory testing environments influenced
      their performance on the examinations. In phase one, 10 third-year students were
      interviewed to generate perception items to which five anatomy lecturers assigned
      content validity. In phase two, students' gross anatomical knowledge was assessed
      by examinations in two modes and their perceptions were examined using the
      devised survey instrument. Forty-five second-year chiropractic students
      voluntarily participated in Phase Two. The two randomly allocated groups
      completed the examinations in a sequential cross-over manner. Student performance
      on the gross anatomy examination was not different between traditional
      "steeplechase" (mean +/- standard deviation (SD): 69 +/- 11%) and online (68 +/-
      15%) modes. The majority of students (87%) agreed that they felt comfortable
      using computers for gross anatomy examinations. However, fewer students found it
      easy to orientate images of cadaver specimens online. The majority of students
      (85%) agreed that they felt comfortable working with cadavers but there was less
      agreement on the effect of moving around the laboratory during practical
      examinations. This data will allow anatomists to confidently implement online
      assessments without fear of jeopardizing academic rigor or student performance.

PMID- 25981195
TI  - Assessment of mitral valve disease: a review of imaging modalities.
AB  - OPINION STATEMENT: Mitral valve disease (MVD) related to mitral valve prolapse
      (MVP), coronary artery disease (CAD), and calcific mitral stenosis, is increasing
      in prevalence across the USA and Europe in the context of a longer life
      expectancy and aging population. In developing countries, rheumatic heart disease
      remains a major cause of MVD. Echocardiography represents the primary diagnostic
      modality for assessment of the mitral valve (MV). With the implementation of
      three-dimensional imaging, echocardiography has become an indispensable tool to
      evaluate the morphology, geometry, and function of the MV apparatus in the pre
      operative setting. However, recognition of its limitations and advances in newer
      technologies have led to a growing interest in other imaging modalities such as
      cardiac magnetic resonance (CMR). Although still not widely available, CMR is an
      essential complement to echocardiography, especially when poor image quality,
      significant variability in flow diameter measurements, and geometric assumptions
      of flow orifice preclude accurate quantification of mitral regurgitation on
      echocardiographic images. In addition, CMR can reliably provide quantitative
      determination of ventricular volumes and function, hence facilitating surgical
      decision-making when serial linear echocardiographic measurements are discrepant.
      Finally, CMR assessment of fibrosis using late gadolinium enhancement allows
      better understanding of the interactions between MVD and the myocardium in both
      MVP and MVD related to CAD or other myopathy. In this review, we summarize the
      role of the available imaging modalities in understanding valvular pathology and
      determining severity of regurgitation or stenosis. Recently published valvular
      guidelines highlight the importance of monitoring MVD progression and the shift
      to intervention earlier in the course of disease. In this context, we also
      discuss the potential role of echocardiography and CMR in identifying early
      stages of MVD and/or pre-clinical markers of myocardial dysfunction.

PMID- 25981197
TI  - Synthesis of phosphabenzenes by an iron-catalyzed [2+2+2] cycloaddition reaction
      of diynes with phosphaalkynes.
AB  - A method for the synthesis of phosphabenzenes under iron catalysis is described.
      Thus, the FeI2 -catalyzed [2+2+2] cycloaddition of diynes with phosphaalkynes in
      m-xylene gave a variety of phosphabenzenes in good to high yields (up to 87 %
      yield). 

PMID- 25981196
TI  - Cardiac arrest: the changing incidence of ventricular fibrillation.
AB  - OPINION STATEMENT: There are more than 300,000 out-of-hospital cardiac arrests
      (OHCA) in the USA annually, which can be grouped into those presenting with
      tachyarrhythmic (shockable) rhythms and those presenting with non-tachyarrhythmic
      rhythms. The incidence of tachyarrhythmic rhythms, which include ventricular
      fibrillation (VF) and pulseless ventricular tachycardia (VT), has been noted to
      be progressively decreasing in multiple studies of OHCA. Improved medical and
      surgical therapies for ischemic heart disease, and the widespread use of
      implantable cardiac defibrillators (ICDs), have likely contributed to a declining
      incidence of VF arrest and may result in conversion of an otherwise VF event into
      a pulseless electrical activity (PEA) arrest. As the incidence of VF has
      declined, it is unclear if the absolute incidence of non-tachyarrhythmic rhythms
      has increased or remained largely unchanged. This article discusses the changing
      rates of presenting rhythms in sudden cardiac arrest, the underlying cellular
      mechanisms of PEA, the factors contributing to the relative increase in the rate
      of PEA arrests, and current treatment options.

PMID- 25981198
TI  - Dirigent Protein-Mediated Lignan and Cyanogenic Glucoside Formation in Flax Seed:
      Integrated Omics and MALDI Mass Spectrometry Imaging.
AB  - An integrated omics approach using genomics, transcriptomics, metabolomics (MALDI
      mass spectrometry imaging, MSI), and bioinformatics was employed to study
      spatiotemporal formation and deposition of health-protecting polymeric lignans
      and plant defense cyanogenic glucosides. Intact flax (Linum usitatissimum)
      capsules and seed tissues at different development stages were analyzed.
      Transcriptome analyses indicated distinct expression patterns of dirigent protein
      (DP) gene family members encoding (-)- and (+)-pinoresinol-forming DPs and their
      associated downstream metabolic processes, respectively, with the former
      expressed at early seed coat development stages. Genes encoding (+)-pinoresinol
      forming DPs were, in contrast, expressed at later development stages. Recombinant
      DP expression and DP assays also unequivocally established their distinct
      stereoselective biochemical functions. Using MALDI MSI and ion mobility
      separation analyses, the pinoresinol downstream derivatives, secoisolariciresinol
      diglucoside (SDG) and SDG hydroxymethylglutaryl ester, were localized and
      detectable only in early seed coat development stages. SDG derivatives were then
      converted into higher molecular weight phenolics during seed coat maturation. By
      contrast, the plant defense cyanogenic glucosides, the monoglucosides
      linamarin/lotaustralin, were detected throughout the flax capsule, whereas
      diglucosides linustatin/neolinustatin only accumulated in endosperm and embryo
      tissues. A putative biosynthetic pathway to the cyanogens is proposed on the
      basis of transcriptome coexpression data. Localization of all metabolites was at
      ca. 20 MUm resolution, with the web based tool OpenMSI enabling not only
      resolution enhancement but also an interactive system for real-time searching for
      any ion in the tissue under analysis. 

PMID- 25981200
TI  - Preventive interventions for tendinopathy: A systematic review.
AB  - OBJECTIVES: Tendinopathy, the most prevalent tendon disorder which is considered
      as the clinical diagnosis of pain and dysfunction, is common in sports and its
      prevalence is ever-increasing. Despite the lack of clarity about risk factors,
      various preventive interventions for tendinopathy have been investigated. The
      main objective of this study is to review current preventive interventions for
      tendinopathy in the major regions: ankle, knee, hip, groin, shoulder and elbow.
      DESIGN: A systematic literature search was conducted. METHODS: The PubMed and
      Embase databases were explored to identify articles that met the inclusion
      criteria. The included studies were assessed on methodological quality and data
      was summarized. RESULTS: Ten articles were included that describe a wide variety
      of preventive interventions. These were divided into three categories: stretch
      and exercise interventions, shoe adaptations and other interventions. The
      methodological quality of the studies was moderate to high. Three out of ten
      studies showed a significant beneficial result. CONCLUSIONS: There is limited
      evidence that a long-term intervention including balance training is effective in
      the prevention of patellar and Achilles tendinopathy. Shoe adaptations in the
      form of shock absorbing insoles could have a preventive effect on Achilles
      tendinopathy. Hormone replacement therapy seems to reduce the risk for structural
      Achilles tendon changes in active post-menopausal women. No evidence was found
      for a positive effect of stretching exercises. Prophylactic eccentric training
      and stretching can increase the risk of injury in asymptomatic players with
      patellar tendon abnormalities. A limited amount of studies was available and more
      research is needed on (multifactorial) etiology, risk factors and preventive
      interventions.

PMID- 25981199
TI  - The cytosolic tail of the tumor marker protein Trop2--a structural switch
      triggered by phosphorylation.
AB  - Trop2 is a transmembrane signaling glycoprotein upregulated in stem and carcinoma
      cells. Proliferation-enhancing signaling involves regulated intramembrane
      proteolytic release of a short cytoplasmic fragment, which is later engaged in a
      cytosolic signaling complex. We propose that Trop2 function is modulated by
      phosphorylation of a specific serine residue within this cytosolic region
      (Ser303), and by proximity effects exerted on the cytosolic tail by Trop2
      dimerization. Structural characterization of both the transmembrane (Trop2TM) and
      cytosolic regions (Trop2IC) support this hypothesis, and shows that the central
      region of Trop2IC forms an alpha-helix. Comparison of NMR structures of non
      phosphorylated and phosphorylated forms suggest that phosphorylation of Trop2IC
      triggers salt bridge reshuffling, resulting in significant conformational changes
      including ordering of the C-terminal tail. In addition, we demonstrate that the
      cytosolic regions of two Trop2 subunits can be brought into close proximity via
      transmembrane part dimerization. Finally, we show that Ser303-phosphorylation
      significantly affects the structure and accessibility of functionally important
      regions of the cytosolic tail. These observed structural features of Trop2 at the
      membrane-cytosol interface could be important for regulation of Trop2 signaling
      activity. 

PMID- 25981202
TI  - Image Processing Strategies Based on a Visual Saliency Model for Object
      Recognition Under Simulated Prosthetic Vision.
AB  - Retinal prostheses have the potential to restore partial vision. Object
      recognition in scenes of daily life is one of the essential tasks for implant
      wearers. Still limited by the low-resolution visual percepts provided by retinal
      prostheses, it is important to investigate and apply image processing methods to
      convey more useful visual information to the wearers. We proposed two image
      processing strategies based on Itti's visual saliency map, region of interest
      (ROI) extraction, and image segmentation. Itti's saliency model generated a
      saliency map from the original image, in which salient regions were grouped into
      ROI by the fuzzy c-means clustering. Then Grabcut generated a proto-object from
      the ROI labeled image which was recombined with background and enhanced in two
      ways--8-4 separated pixelization (8-4 SP) and background edge extraction (BEE).
      Results showed that both 8-4 SP and BEE had significantly higher recognition
      accuracy in comparison with direct pixelization (DP). Each saliency-based image
      processing strategy was subject to the performance of image segmentation. Under
      good and perfect segmentation conditions, BEE and 8-4 SP obtained noticeably
      higher recognition accuracy than DP, and under bad segmentation condition, only
      BEE boosted the performance. The application of saliency-based image processing
      strategies was verified to be beneficial to object recognition in daily scenes
      under simulated prosthetic vision. They are hoped to help the development of the
      image processing module for future retinal prostheses, and thus provide more
      benefit for the patients.

PMID- 25981201
TI  - A snapshot of chronic ankle instability in a cohort of netball players.
AB  - OBJECTIVES: Ankle injuries account for the highest percentage of injuries in
      netball, yet the chronic nature of ankle sprains is under reported within this
      population group. Chronic ankle instability is a term used to describe certain
      insufficiencies that persist after an acute ankle sprain. The aim of this study
      was to investigate recurrent sprain, perceived ankle instability and mechanical
      ankle instability in a cohort of netball players. DESIGN: Cross-sectional study.
      METHODS: Ninety-six female netball players (24.1+/-7.9 years) were recruited (42
      club players and 54 inter-district players). Recurrent sprain was defined as two
      or more lifetime sprains to the same ankle. Perceived ankle instability was
      quantified with the Cumberland Ankle Instability Tool - Youth. Mechanical ankle
      instability was quantified via inversion-eversion rotations using an ankle
      arthrometer at torques of 3Nm. RESULTS: Forty-seven percent of the cohort had
      recurrently sprained an ankle. Of the 69 players with a previously sprained
      ankle, 64% had a moderate-severe degree of perceived ankle instability. The total
      inversion-eversion angle was 31.1+/-8.7 degrees. Club players had more cases of
      moderate-severe perceived ankle instability (p=0.01) and larger inversion
      eversion angles (p=0.001) compared to inter-district players. CONCLUSIONS:
      Recurrent ankle sprain and perceived ankle instability are easily identifiable
      aspects of chronic ankle instability shown to be prevalent within this cohort.
      Additional research is required to quantify a cut-off value for mechanical
      instability. Club netball players were found to have more counts of moderate
      severe perceived ankle instability and larger inversion-eversion angles when
      compared to the inter-district netball players.

PMID- 25981203
TI  - Regulatory T cells: first steps of clinical application in solid organ
      transplantation.
AB  - Solid organ transplantation is the treatment of choice for patients with end
      stage organ failure. To prevent rejection of the transplanted organ continuous
      treatment with immunosuppressive medication is needed. Immunosuppression may be
      harmful to the transplant recipient, increasing the risk of cancer, infections
      and cardiovascular disease. To improve transplant and patient survival, there is
      a need for an immune-modulatory regimen that is not only potent in preventing
      rejection of the transplanted organ, but has less side effects compared to
      current immunosuppressive regimens. Increasingly, transplantation research
      focusses on regulatory T cell (Treg) therapy to achieve this aim, in which Treg
      are used as a strategy to allow reduction of immunosuppression. Currently, the
      first clinical trials are underway investigating the safety and feasibility of
      Treg therapy in renal transplantation. This review gives an overview of the
      rationale of using Treg therapy in transplantation, previous experience with Treg
      therapy in humans, and the expected safety, potential efficacy and cost
      effectiveness of Treg therapy in solid organ transplantation. 

PMID- 25981204
TI  - The role of a dominant predator in shaping biodiversity over space and time in a
      marine ecosystem.
AB  - 1. Exploitation of living marine resources has resulted in major changes to
      populations of targeted species and functional groups of large-bodied species in
      the ocean. However, the effects of overfishing and collapse of large top
      predators on the broad-scale biodiversity of oceanic ecosystems remain largely
      unexplored. 2. Populations of the Atlantic cod (Gadus morhua) were overfished and
      several collapsed in the early 1990s across Atlantic Canada, providing a unique
      opportunity to study potential ecosystem-level effects of the reduction of a
      dominant predator on fish biodiversity, and to identify how such effects might
      interact with other environmental factors, such as changes in climate, over time.
      3. We combined causal modelling with model selection and multimodel inference to
      analyse 41 years of fishery-independent survey data (1970-2010) and quantify
      ecosystem-level effects of overfishing and climate variation on the biodiversity
      of fishes across a broad area (172 000 km(2) ) of the Scotian Shelf. 4. We found
      that alpha and beta diversity increased with decreases in cod occurrence; fish
      communities were less homogeneous and more variable in systems where cod no
      longer dominated. These effects were most pronounced in the colder north-eastern
      parts of the Scotian Shelf. 5. Our results provide strong evidence that intensive
      harvesting (and collapse) of marine apex predators can have large impacts on
      biodiversity, with far-reaching consequences for ecological stability across an
      entire ecosystem.

PMID- 25981205
TI  - Patients with chronic non-specific low back pain who reported reduction in pain
      and improvement in function also demonstrated an improvement in gait pattern.
AB  - PURPOSE: To assess the changes in gait pattern and clinical symptoms of patients
      with chronic non-specific low back pain (CNSLBP) following a home-based
      biomechanical treatment (HBBT). METHODS: This was a retrospective analysis of 60
      CNSLBP patients. All patients underwent a gait evaluation and completed self
      assessment questionnaires at pre-treatment and after 3 and 6 months of a HBBT
      (AposTherapy). Twenty-four healthy, aged-matched individuals served as a
      reference group. RESULTS: Significant differences were found in all gait
      parameters and clinical symptoms between patients with CNSLBP and healthy people
      before treatment. Significant improvements were found in all gait parameters and
      clinical measures following 6 months of therapy including an increase in gait
      velocity (10.6 %), step length (5.6 %), cadence (5 %), and quality of life and a
      decrease in pain (13.3 %). There were no significant differences between groups
      in the gait parameters following 6 months of treatment. CONCLUSIONS: Significant
      differences exist between patients with CNSLBP and healthy controls in terms of
      gait pattern and self-assessed health status. The examined HBBT led to
      significant improvements in gait pattern, reduction in pain, improved function
      and increased quality of life. However, future studies should validate these
      results while comparing this treatment to other treatment modalities.

PMID- 25981206
TI  - Comparison of spinal deformity in children with Chiari I malformation with and
      without syringomyelia: matched cohort study.
AB  - PURPOSE: To describe curve patterns in patients with Chiari malformation I (CIM)
      without syringomyelia, and compare to patients with Chiari malformation with
      syringomyelia (CIM + SM). METHODS: Review of medical records from 2000 to 2013 at
      a single institution was performed to identify CIM patients with scoliosis.
      Patients with CIM were matched (1:1) by age and gender to CIM + SM. Radiographic
      curve patterns, MRI-based craniovertebral junction parameters, and associated
      neurological signs were compared between the two cohorts. RESULTS: Eighteen
      patients with CIM-associated scoliosis in the absence of syringomyelia were
      identified; 14 (78 %) were female, with mean age of 11.5 +/- 4.5 years. Mean
      tonsillar descent was 9.9 +/- 4.1 mm in the CIM group and 9.1 +/- 3.0 mm in the
      CIM + SM group (p = 0.57). Average syrinx diameter in the CIM + SM group was 9.0
      +/- 2.7 mm. CIM patients demonstrated less severe scoliotic curves (32.1 degrees 
      vs. 46.1 degrees , p = 0.04), despite comparable thoracic kyphosis (43.7 degrees 
      vs. 49.6 degrees , p = 0.85). Two (11 %) patients with CIM demonstrated thoracic
      apex left deformities compared to 9/18 (50 %) in the CIM + SM cohort (p = 0.01).
      Neurological abnormalities were only observed in the group with syringomyelia
      (6/18, or 33 %; p = 0.007). CONCLUSION: In the largest series specifically
      evaluating CIM and scoliosis, we found that these patients appear to present with
      fewer atypical curve features, with less severe scoliotic curves, fewer apex left
      curves, and fewer related neurological abnormalities than CIM + SM. Notably,
      equivalent thoracic kyphosis was observed in both groups. Future studies are
      needed to better understand pathogenesis of spinal deformity in CIM with and
      without SM.

PMID- 25981207
TI  - Instability-Assisted Direct Writing of Microstructured Fibers Featuring
      Sacrificial Bonds.
AB  - A 30 MUm-diameter thread of poly(lactic acid) (PLA) dissolved in dichloromethane
      is deposited on top of the eye of a sewing needle. The deposition robot traces a
      straight line; the helical shape of the thread is due to the liquid rope coiling
      instability. This instability is used to fabricate microstructured fibers with
      tailored mechanical properties. 

PMID- 25981208
TI  - The role of inflammation and microglial activation in the pathophysiology of
      psychiatric disorders.
AB  - Psychiatric disorders, including major depressive disorder (MDD), bipolar
      disorder (BD) and schizophrenia, affect a significant percentage of the world
      population. These disorders are associated with educational difficulties,
      decreased productivity and reduced quality of life, but their underlying
      pathophysiological mechanisms are not fully elucidated. Recently, studies have
      suggested that psychiatric disorders could be considered as inflammatory
      disorders, even though the exact mechanisms underlying this association are not
      known. An increase in inflammatory response and oxidative stress may lead to
      inflammation, which in turn can stimulate microglia in the brain. Microglial
      activation is roused by the M1 phenotype, which is associated with an increase in
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). On the
      contrary, M2 phenotype is associated with a release of anti-inflammatory
      cytokines. Thus, it is possible that the inflammatory response from microglial
      activation can contribute to brain pathology, as well as influence treatment
      responses. This review will highlight the role of inflammation in the
      pathophysiology of psychiatric disorders, such as MDD, BD, schizophrenia, and
      autism. More specifically, the role of microglial activation and associated
      molecular cascades will also be discussed as a means by which these
      neuroinflammatory mechanisms take place, when appropriate.

PMID- 25981209
TI  - Effects of combined nicotine and fluoxetine treatment on adult hippocampal
      neurogenesis and conditioned place preference.
AB  - Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal
      subarea. It is known to be induced by antidepressant treatment and reduced in
      response to nicotine administration. We checked here whether the antidepressant
      fluoxetine would inverse the decrease in hippocampal neurogenesis caused by
      nicotine. It is shown that repeated, but not a single injection of rats with
      fluoxetine was able to abolish the decrease in adult dentate cell proliferation
      produced by nicotine treatment. We measured the expression of several biochemical
      parameters known to be associated with neurogenesis in the dentate gyrus. Both
      drugs increased the expression of p75 neurotrophin receptor, which promotes
      proliferation and early maturation of dentate gyrus cells. Using the conditioned
      place preference (CPP) paradigm, we also gave both drugs in a context in which
      their rewarding properties could be measured. Fluoxetine produced a significant
      but less robust CPP than nicotine. A single injection of fluoxetine was found to
      reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were
      completely abolished in response to repeated fluoxetine injections. Expression of
      nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP
      responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression
      in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to
      nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able
      to disrupt the association between nicotine and the environment, this
      antidepressant may be tested as a treatment for nicotine addiction using cue
      exposure therapy.

PMID- 25981211
TI  - Life course research: new opportunities for establishing social and biological
      plausibility.

PMID- 25981210
TI  - US State-level income inequality and risks of heart attack and coronary risk
      behaviors: longitudinal findings.
AB  - OBJECTIVES: To examine prospectively the association between US state income
      inequality and incidence of heart attack. METHODS: We used data from the National
      Epidemiologic Survey on Alcohol and Related Conditions (n = 34,445). Respondents
      completed interviews at baseline (2001-2002) and follow-up (2004-2005). Weighted
      multilevel modeling was used to determine if US state-level income inequality
      (measured by the Gini coefficient) at baseline was a predictor of heart attack
      during follow-up, controlling for individual-level and state-level covariates.
      RESULTS: In comparison to residents of US states in the lowest quartile of income
      inequality, those living in the second [Adjusted Odds Ratio (AOR) = 1.71, 95 % CI
      1.16-2.53)], third (AOR = 1.81, 95 % CI 1.28-2.57), and fourth (AOR = 2.04, 95 %
      CI 1.26-3.29) quartiles were more likely to have a heart attack. Similar findings
      were obtained when we excluded those who had a heart attack prior to baseline.
      CONCLUSIONS: This study is one of the first to empirically show the longitudinal
      relationship between income inequality and coronary heart disease. Living in a
      state with higher income inequality increases the risk for heart attack among US
      adults.

PMID- 25981212
TI  - Subtentorial cerebral nocardiosis in immunocompetent patients: CT and MR imaging
      findings.
AB  - PURPOSE: To describe the clinical presentation and computed tomography (CT) and
      magnetic resonance imaging (MRI) appearances of subtentorial nocardia cerebral
      abscesses developing in immunocompetent patients. PATIENTS AND METHODS: The
      clinical findings and the results of CT and MRI examinations of three
      immunocompetent patients with nocardiosis located initially only in the
      subtentorial region were studied. Three patients underwent CT examination and two
      patients had MRI. RESULTS: Clinically, two patients had cerebellar syndrome and
      the third had meningism with fever. The diagnosis of nocardiosis was
      bacteriologically confirmed by demonstrating the organism in lumbar puncture
      fluid in one patient and by an aspiration biopsy of the abscess in the other two.
      Two of the patients improved under targeted antibiotic therapy whereas the third
      patient died. The main imaging features of the lesions were a multiloculated
      appearance with peripheral enhancement after intravenous administration of
      iodinated contrast material on CT and a multicystic appearance on MRI, with a
      peripheral hypointense rim on T2-weighted images, a relatively minor mass effect
      and a multiloculated appearance on gadolinium-chelate enhanced T1-weighted
      images. CONCLUSION: The clinical presentation of cerebral nocardiosis is
      relatively non-specific. A microcystic lesion surrounded by hypointensity on T2
      weighted MR images with a multiloculated pattern after gadolinium chelate
      administration on T1-weighted MR images in association with a relatively minor
      mass effect should suggest this diagnosis even if the lesion is single and in the
      absence of immunosuppression.

PMID- 25981213
TI  - Treatment of hepatocellular carcinomas by thermal ablation and hepatic
      transarterial chemoembolization.
AB  - Local tumor recurrence after thermal ablation of hepatocellular carcinoma (HCC)
      can impact on overall survival and are very closely linked to partial treatment
      of the primary lesion or to potential microvascular invasion or satellite
      micronodules located close to the main lesion. The diagnosis of these liver
      metastases close to the primary lesion on CT and MRI is difficult and their
      incidence, number and spread throughout the liver correlates with diameter of
      primary tumor. Tumor diameter is currently the key factor to predict whether or
      not thermal ablation of HCC will be complete or not. It has now been shown for
      monopolar radiofrequency ablation that this therapy alone is sufficient to
      effectively treat single HCCs<3cm in diameter provided that liver micrometastases
      are not present. If the HCC is>3cm in size, multifocal or in the case of tumor
      recurrence, overall survival and recurrence-free survival results are better if
      monopolar radiofrequency ablation is combined with hepatic trans-arterial
      chemoembolization. The timing of this combination of treatments probably
      influences its effectiveness on tumor and tolerability and remains to be
      assessed. 

PMID- 25981214
TI  - Ablative therapies: Advantages and disadvantages of radiofrequency, cryotherapy,
      microwave and electroporation methods, or how to choose the right method for an
      individual patient?
AB  - Several ablation techniques are currently available. Except for electroporation,
      all of these methods cause fatal damage at a cellular level and irreversible
      architectural deconstruction at a tissue level by thermal effects. Ablation of a
      tumor using one of these techniques, whether thermal or otherwise, requires
      applicators to be positioned from which the energy is delivered in situ. Some
      techniques, however, require several applicators to be inserted (multibipolar
      radiofrequency, cryotherapy and electroporation) whereas a single applicator is
      often sufficient with other technologies (monopolar radiofrequency and
      microwave). These methods are conceptually very similar but are distinguished
      from each other in practice through the technologies they use. It is essential to
      understand these differences as they influence the advantages and limitations of
      each of the techniques. There is no such thing as the perfect multifunctional
      ablation device and choice is dictated on an individual patient basis depending
      on the aim of treatment, which itself depends on each patient's clinical
      situation. 

PMID- 25981215
TI  - Contrast-induced nephropathy following chronic total occlusion percutaneous
      coronary intervention in patients with chronic kidney disease.
AB  - OBJECTIVES: Contrast-induced nephropathy (CIN) has not been systematically
      studied in high-risk patients with chronic kidney disease (CKD) undergoing
      percutaneous coronary intervention (PCI) for chronic total occlusion (CTO).
      METHODS: We prospectively observed 515 consecutive patients with CKD undergoing
      PCI. Patients were divided into three groups: patients who underwent attempted
      PCI for CTO (group A, n = 85), patients who did not receive PCI for CTO (group B,
      n = 45) and patients without CTO (group C, n = 385). RESULTS: CIN developed in 55
      patients (10.68 %). Group A patients received a larger CM dose than group B or
      group C (p = 0.024). The intravenous hydration volume, age and CIN Mehran score
      were not significantly different between the three groups. The incidence of CIN
      was 9.4 % for group A, 6.7 % for group B and 11.4 % for group C (p = 0.344). In
      hospital mortality and required renal replacement therapy (p = 0.325) were not
      significantly different between the groups. Multivariate analysis showed that
      after adjusting for potential confounding factors, the odds ratio for CIN was
      1.03 (p = 0.944) for group A and 0.64 for group B (p = 0.489) compared to group
      C. CONCLUSIONS: Attempts to achieve recanalization of CTO in patients with CKD
      might not increase the risk of CIN if appropriate preventative measures are
      taken. KEY POINTS: * Contrast-induced nephropathy can increase morbidity and
      mortality * Chronic kidney disease patients are at the greatest risk of CIN *
      Patients with CKD undergoing CTO-PCI are common * Incidence of CIN has not been
      reported in CKD patients * CTO-PCI in CKD patients might not increase the risk of
      CIN.

PMID- 25981216
TI  - In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution
      Ultrasound and bench-top Magnetic Resonance Imaging in Mice.
AB  - OBJECTIVE: The aim of this study was to establish and evaluate (colour Doppler-)
      high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging
      (btMRI) as new methods to monitor experimental colitis. MATERIALS AND METHODS:
      hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in
      mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous
      treatment with infliximab (n = 19). RESULTS: Determination of colon wall
      thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic
      areas by btMRI allowed discrimination between the treatment groups (mean a vs. b
      vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm).
      btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring
      (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p <
      0.05). CONCLUSIONS: The innovative in vivo techniques btMRI and hrUS are safe and
      technically feasible. They differentiate between distinct grades of colitis in an
      experimental setting, and correlate with established post-mortem parameters. In
      addition to endoscopic procedures, these techniques provide information regarding
      colon wall thickness and perfusion. Depending on the availability of these
      techniques, their application increases the value of in vivo monitoring in
      experimental acute colitis in small rodents. KEY POINTS: * Improved in vivo
      monitoring might balance interindividual differences in murine colitis. * In
      monitoring murine colitis, btMRI and hrUS are safe and technically feasible. *
      Very short examination times underline the usefulness especially of hrUS. *
      Results of btMRI and hrUS correlate with endoscopic and post-mortem findings.

PMID- 25981217
TI  - Embolization of renal arteries before transplantation in patients with polycystic
      kidney disease: a single institution long-term experience.
AB  - PURPOSE: We aimed to retrospectively assess the long-term safety and efficacy of
      embolization of renal arteries (ERA) in patients with polycystic kidney disease
      (PKD) before renal transplantation. MATERIAL AND METHODS: Between January 2008
      and November 2013, 82 ERA procedures were performed on 76 kidneys in 73 patients
      (mean age 53 years, range: 34-72). All patients had terminal-stage PKD and were
      under dialysis and on the renal transplant waiting list with a temporary
      contraindication due to excessive renal volume. RESULTS: ERA was considered
      successful in 89.5% (68/76) of embolized kidneys, meaning that the temporary
      contraindication for transplantation could be withdrawn for 65 patients (on
      average 5.6 months, range: 2.8-24.3, after ERA). Mean volume reduction was 40
      (range: 2-69) at 3 months and 59% (35-86) thereafter (both p < 0.001). Post
      embolization syndrome occurred after 15 of 82 procedures (18.3%). The severe
      complication rate was 4.9%. Forty-three (67.7%) transplantations were
      successfully conducted after ERA, with a mean follow-up of 26.2 months (range:
      1.8-59.5), and the estimated 5-year graft survival rate was 95.3% [95% CI: 82.7
      98.8]. CONCLUSIONS: ERA is a safe and effective alternative to nephrectomy before
      renal transplantation in patients with PKD. KEY POINTS: * Embolization of non
      functioning polycystic kidneys allowed transplantation in 89.5% of cases. *
      Technical failure rate was 7.9% after embolization, irrespective of the technique
      used. * Post-embolization syndrome occurred after 18.3% of the procedures. * A
      low rate of severe complications (4.9%) was observed after renal embolization.

PMID- 25981218
TI  - A prospective study on contrast-enhanced magnetic resonance imaging of testicular
      lesions: distinctive features of Leydig cell tumours.
AB  - OBJECTIVES: Up to 20 % of incidentally found testicular lesions are benign Leydig
      cell tumours (LCTs). This study evaluates the role of contrast-enhanced magnetic
      resonance imaging (MRI) in the identification of LCTs in a large prospective
      cohort study. MATERIALS AND METHODS: We enrolled 44 consecutive patients with at
      least one solid non-palpable testicular lesion who underwent scrotal MRI. Margins
      of the lesions, signal intensity and pattern of wash-in and wash-out were
      analysed by two radiologists. The frequency distribution of malignant and benign
      MRI features in the different groups was compared by using the chi-squared or
      Fisher's exact test. Sensitivity, specificity, positive and negative predictive
      value, and diagnostic accuracy were calculated. RESULTS: The sensitivity of
      scrotal MRI to diagnose LCTs was 89.47 % with 95.65 % specificity; sensitivity
      for malignant lesions was 95.65 % with 80.95 % specificity. A markedly
      hypointense signal on T2-WI, rapid and marked wash-in followed by a prolonged
      washout were distinctive features significantly associated with LCTs. Malignant
      lesions were significantly associated with blurred margins, weak hypointense
      signal on T2-WI ,and weak and progressive wash-in. The overall diagnostic
      accuracy was 93 %. CONCLUSIONS: LCTs have distinctive contrast-enhanced MRI
      features that allow the differential diagnosis of incidental testicular lesions.
      KEY POINTS: * MRI is able to characterize testicular lesions suggesting a
      specific diagnosis. * Rapid and marked wash-in is a common feature of Leydig cell
      tumours. * Markedly hypointense T2-WI signal is significantly correlated with
      benign lesions. * Blurred margins and weak hypointense T2-WI signal are
      correlated with malignant tumours. * Weak and progressive wash-in features are
      present in 85 % of seminomatous lesions.

PMID- 25981219
TI  - An anatomical study of the indirect tendon of the rectus femoris using
      ultrasonography.
AB  - The aim of this study was to demonstrate that ultrasound can allow a precise
      assessment of the indirect tendon of the rectus femoris using a new lateral
      approach. METHODS AND MATERIALS: Four hips were dissected for the anatomical
      study of the proximal rectus femoris insertions. Under ultrasonographic guidance,
      spinal needles piercing the direct tendon were placed in the indirect tendon,
      following by dissection. Then, high-resolution ultrasound was performed in 20
      volunteers with assessment of the indirect tendon of the rectus femoris. RESULTS:
      At dissection, the spinal needles were located in or immediately adjacent to the
      indirect tendon, thus confirming that it was correctly depicted by ultrasound.
      The indirect tendon could be identified in each cadaver and each volunteer with
      ultrasound. The optimal position of the probe to allow assessment of the indirect
      tendon could be defined. No significant changes in the appearance or thickness of
      the tendon could be observed. CONCLUSION: The results of our study showed that
      the indirect tendon of the rectus femoris muscle can be clearly depicted by
      sonography in healthy adult subjects. The potential applications of this new use
      of sonography must now be confirmed by clinical studies. KEY POINTS: * The
      anatomy of the proximal rectus femoris is reviewed * Until now, sonography was
      limited for assessing direct and conjoined tendons * The indirect tendon can be
      clearly depicted by sonography * A new lateral approach for studying the indirect
      tendon is described.

PMID- 25981220
TI  - Hypodense liver lesions in patients with hepatic steatosis: do we profit from
      dual-energy computed tomography?
AB  - PURPOSE: To evaluate dual-energy CT (DECT) imaging of hypodense liver lesions in
      patients with hepatic steatosis, having a high incidence in the general
      population and among cancer patients receiving chemotherapy. METHODS: One hundred
      and five patients with hepatic steatosis (liver parenchyma <40 HU) underwent
      contrast-enhanced DECT with reconstruction of pure iodine (PI), optimum contrast
      (OC), 80 kVp, and 120 kVp-equivalent data sets. Image noise (IN), lesion to liver
      signal to noise (SNR) and contrast to noise (CNR) ratios were quantitatively
      analysed; image quality was rated on a 5-point scale (1, excellent; 2, good; 3,
      fair; 4, poor; 5, non-diagnostic) by two independent reviewers. RESULTS: In 21
      patients with hypodense liver lesions, IN was lowest in PI followed by 120 kVp
      equivalent and OC, and highest in 80 kVp. SNR was highest in PI (1.30), followed
      by 120 kVp-equivalent (0.72) and 80 kVp (0.63), and lowest in OC (0.55). CNR was
      highest in 120 kVp-equivalent (4.95), followed by OC (4.55) and 80 kVp (4.14),
      and lowest in PI (3.63). The 120 kVp-equivalent series exhibited best overall
      qualitative image score (1.88), followed by OC (1.98), 80 kVp (3.00) and PI
      (3.67). CONCLUSION: In our study, the 120 kVp-equivalent series was best suited
      for visualization of hypodense lesions within steatotic liver parenchyma, while
      using DECT currently seems to offer no additional diagnostic advantage. KEY
      POINTS: * Hepatic steatosis has high incidence in the general population and
      following chemotherapy. * Hypodense liver lesions can be obscured by steatotic
      liver parenchyma in CT. * Low kV p -CT shows no advantage in detecting hypodense
      lesions in steatotic livers. * Additional DECT image information does not improve
      visualization of hypodense lesions in steatosis. * 120 kV p -equivalent imaging
      yields best quantitative and qualitative image analysis results.

PMID- 25981221
TI  - Accuracy of simple plain radiographic signs and measures to diagnose acute
      scapholunate ligament injuries of the wrist.
AB  - OBJECTIVE: To determine the accuracy of common radiological indices for
      diagnosing ruptures of the scapholunate (SL) ligament, the most relevant soft
      tissue injury of the wrist. METHODS: This was a prospective diagnostic accuracy
      study with independent verification of index test findings by a reference
      standard (wrist arthroscopy). Bilateral digital radiographs in posteroanterior
      (pa), lateral and Stecher's projection were evaluated by two independent expert
      readers. Diagnostic accuracy of radiological signs was expressed as sensitivity,
      specificity, positive (PPV) and negative (NPV) predictive values with 95 %
      confidence intervals (CI). RESULTS: The prevalence of significant acute SL tears
      (grade >= III according to Geissler's classification) was 27/72 (38 %, 95 % CI 26
      50 %). The SL distance on Stecher's projection proved the most accurate index to
      rule the presence of an SL rupture in and out. SL distance on plain pa
      radiographs, Stecher's projection and the radiolunate angle contributed
      independently to the final diagnostic model. These three simple indices explained
      97 % of the diagnostic variance. CONCLUSIONS: In the era of computed tomography
      and magnetic resonance imaging, plain radiographs remain a highly sensitive and
      specific primary tool to triage patients with a suspected SL tear to further
      diagnostic work-up and surgical care. KEY POINTS: * Scapholunate ligament (SL)
      lesions are the most relevant soft tissue wrist injuries. * Missed and untreated
      SL ruptures can cause painful and disabling post-traumatic wrist osteoarthritis.
      * Reliable threshold values of radiographic indices should prompt further imaging
      or surgical care. * Plain radiographs deliver conclusive clinical information if
      certain hand positions are used.

PMID- 25981222
TI  - Quantitative CT analysis of pulmonary ground-glass opacity nodules for
      distinguishing invasive adenocarcinoma from non-invasive or minimally invasive
      adenocarcinoma: the added value of using iodine mapping.
AB  - OBJECTIVES: To determine whether quantitative analysis of iodine-enhanced images
      generated from dual-energy CT (DECT) have added value in distinguishing invasive
      adenocarcinoma from non-invasive or minimally invasive adenocarcinoma (MIA)
      showing ground-glass nodule (GGN). METHODS: Thirty-four patients with 39 GGNs
      were enrolled in this prospective study and underwent DECT followed by complete
      tumour resection. Various quantitative imaging parameters were assessed,
      including virtual non-contrast (VNC) imaging and iodine-enhanced imaging.
      RESULTS: Of all 39 GGNs, four were adenocarcinoma in situ (AIS) (10 %), nine were
      MIA (23 %), and 26 were invasive adenocarcinoma (67 %). When assessing only VNC
      imaging, multivariate analysis revealed that mass, uniformity, and size-zone
      variability were independent predictors of invasive adenocarcinoma (odds ratio
      [OR] = 19.92, P = 0.02; OR = 0.70, P = 0.01; OR = 16.16, P = 0.04, respectively).
      After assessing iodine-enhanced imaging with VNC imaging, both mass on the VNC
      imaging and uniformity on the iodine-enhanced imaging were independent predictors
      of invasive adenocarcinoma (OR = 5.51, P = 0.04 and OR = 0.67, P < 0.01). The
      power of diagnosing invasive adenocarcinoma was improved after adding the iodine
      enhanced imaging parameters versus VNC imaging alone, from 0.888 to 0.959,
      respectively (P = 0.029). CONCLUSION: Quantitative analysis using iodine-enhanced
      imaging metrics versus VNC imaging metrics alone generated from DECT have added
      value in distinguishing invasive adenocarcinoma from AIS or MIA. KEY POINTS:
      Quantitative analysis using DECT was used to distinguish invasive adenocarcinoma.
      Tumour mass and uniformity were independent predictors of invasive
      adenocarcinoma. Diagnostic performance was improved after adding iodine
      parameters to VNC parameters.

PMID- 25981223
TI  - Testing the "Sexually Abused-Abuser Hypothesis" in Adolescents: A Population
      Based Study.
AB  - A long-standing belief in the literature on sex offenders is that sexually
      victimized youths are at increased risk of becoming sex offenders themselves. The
      present study tested the link between past sexual abuse, either with or without
      contact, and sexually offending behavior in a representative sample of male and
      female adolescents while controlling for other types of abuse, mental health
      problems, substance use, and non-sexual violent behaviors. Self-reported data
      were collected from a nationally representative sample of 6,628 students
      attending 9th grade public school in Switzerland (3,434 males, 3,194 females,
      mean age = 15.50 years, SD = 0.66 years). Exposure to contact and non-contact
      types of sexual abuse was assessed using the Child Sexual Abuse Questionnaire and
      sexually offending behavior by the presence of any of three behaviors indicating
      sexual coercion. Two-hundred-forty-five males (7.1 %) and 40 females (1.2 %)
      reported having sexually coerced another person. After controlling for non-sexual
      abuse, low parent education, urban versus rural living, mental health problems,
      substance use, and non-sexual violent behavior, male adolescents who were victims
      of contact sexual abuse and non-contact sexual abuse were significantly more
      likely to report coercive sexual behaviors. Females who experienced contact or
      non-contact sexual abuse were also found at increased risk of committing sexual
      coercion after controlling for covariates. The present findings demonstrate a
      strong relationship between past sexual abuse, with and without physical contact,
      and sexual-offending behavior in male and female adolescents. Reducing exposure
      to non-contact sexual abuse (like Internet-based sexual exploitation) should
      become a new area of sexual violence prevention in youths.

PMID- 25981224
TI  - Serum oxidant and antioxidant status of patients with chronic tension-type
      headache: possible effects of medical treatment.
AB  - Tension-type headache (TTH) is one of the most common and costly primary types of
      headache in clinical practice, with an unknown etiology. This study assessed to
      investigate oxidative and antioxidative status in patients with chronic tension
      type headache (CTTH), and to evaluate possible effect of medical treatment. The
      study included 41 CTTH patients and 19 age- and sex-matched healthy subjects
      without headache as controls. The CTTH group comprised 20 patients receiving
      treatment and 21 untreated patients. We evaluated oxidant/antioxidant status by
      measuring serum malondialdehyde (MDA) levels and activities of antioxidant
      enzymes, namely glutathione peroxidase (GSH-Px) and catalase (CAT). Comparison of
      oxidative parameters in the patient and control groups revealed significantly
      lower CAT activities and higher MDA level and GSH-Px activities in the patient
      group. In the CTTH group, serum CAT activities were found to be significantly
      decreased in patient groups, while serum MDA levels and GSH-Px activities were
      found to be higher in the untreated CTTH patients. These findings suggest that
      oxidative stress is increased in the patients with CTTH, and medical treatment
      abolishes the stress in part. It has been concluded that antioxidant support
      might be helpful for the patients with CTTH to prevent oxidant stress and
      peroxidation damages further. 

PMID- 25981227
TI  - Isolated transient eyelid lag in multiple sclerosis.

PMID- 25981225
TI  - CT perfusion cerebral blood volume does not always predict infarct core in acute
      ischemic stroke.
AB  - We investigated the practical clinical utility of the CT perfusion (CTP) cerebral
      blood volume (CBV) parameter for differentiating salvageable from non-salvageable
      tissue in acute ischemic stroke (AIS). Fifty-five patients with AIS were imaged
      within 6 h from onset using CTP. Admission CBV defect (CBVD) volume was outlined
      using previously established gray and white matter CBV thresholds for infarct
      core. Admission cerebral blood flow (CBF) hypoperfusion and CBF/CBV mismatch were
      visually evaluated. Truncation of the ischemic time-density curve (ITDC) and
      hypervolemia status at admission, recanalization at 24-h CT angiography,
      hemorrhagic transformation (HT) at 24 h and/or 7-day non-contrast CT (NCCT),
      final infarct volume as indicated by 3-month NCCT defect (NCCTD) and 3-month
      modified Rankin Score were determined. Patients with recanalization and no
      truncation had the highest correlation (R = 0.81) and regression slope (0.80)
      between CBVD and NCCTD. Regression slopes were close to zero for patients with
      admission hypervolemia with/without recanalization. Hypervolemia underestimated
      (p = 0.02), while recanalization and ITDC truncation overestimated (p = 0.03) the
      NCCTD. Among patients with confirmed recanalization at 24 h, 38 % patients had an
      admission CBF/CBV mismatch within normal appearing areas on respective NCCT. 83 %
      of these patients developed infarction in admission hypervolemic CBF/CBV mismatch
      tissue. A reduction in CBV is a valuable predictor of infarct core when the
      acquisition of ITDC data is complete and hypervolemia is absent within the tissue
      destined to infarct. Raised or normal CBV is not always indicative of salvageable
      tissue, contrary to the current definition of penumbra.

PMID- 25981228
TI  - A fatal case of cerebral aspergillosis in a diabetes mellitus patient.

PMID- 25981226
TI  - Glutathione S-transferases variants as risk factors in Alzheimer's disease.
AB  - Glutathione S-transferase (GST) was suggested as an important contributor to
      Alzheimer's disease (AD). The GSTs polymorphisms have been investigated as
      candidate genetic risk factors for AD, yet results remained uncertain. Therefore,
      we performed a meta-analysis to clarify the relationship of GSTs polymorphisms
      with the occurrence of AD. PubMed, Embase, Cochrane library and Alzgene databases
      were searched and potential literatures were selected. Pooled analyses and
      subgroup analyses were conducted, and also publication bias tests and cumulative
      meta-analysis. This meta-analysis suggested null associations between
      polymorphisms of GSTM1, GSTT1, GSTM3, GSTP1, GSTO1 and AD risk. GSTs variants may
      not have an impact on the morbidity of Alzheimer's disease. Further well designed
      researches are required to confirm these findings of the current study. 

PMID- 25981229
TI  - Cortical laminar necrosis following the rapid correction of drug-induced
      hyponatremia.

PMID- 25981230
TI  - The Italian version of the Brain Injury Rehabilitation Trust (BIRT) personality
      questionnaires: five new measures of personality change after acquired brain
      injury.
AB  - The aim of this study was to describe the translation and adaptation of the BIRT
      personality questionnaires for the Italian population. This included the
      replication of validity testing and the collection of normative data. Following
      translation and adaptation according to cross-cultural guidelines, the
      questionnaires were administered as a pre-test to a sample of 20 healthy subjects
      and then to 10 patients. The questionnaires were then administered to 120 healthy
      subjects equally distributed by sex, education, and age, to collect normative
      data from an Italian population. The questionnaires were easily administered to
      both healthy subjects and patients. Statistical analysis on normative data was
      conducted to find the mean value for each questionnaire. This study lays the
      foundations for using a new instrument to assess behavioral changes after
      acquired brain injury on the Italian population. 

PMID- 25981231
TI  - Levodopa alone compared with levodopa-sparing therapy as initial treatment for
      Parkinson's disease: a meta-analysis.
AB  - To assess the long-term use of L-dopa alone vs L-dopa-sparing therapy, as initial
      treatment, provides the most efficient long-term control of symptoms and best
      quality of life for people with early Parkinson's disease (PD). PubMed; Google
      scholar; Cochrane Central Register of Controlled Trials and the Web of Science
      were searched for randomised, placebo-controlled trials (RCTs) on L-dopa alone
      and L-dopa sparing as initial treatment in early PD patients. We used a random
      effects model rather than a fixed effects model because of this takes into
      account heterogeneity between multi-studies. Eleven RCTs were included. The
      results showed that L-dopa alone could evidently improve the UPDRS part I (p =
      0.005), part II (p < 0.0001), part III (p < 0.0001) and UPDRS total score (p =
      0.004) compared with L-dopa-sparing therapy in PD patients. Meanwhile, a reduced
      risk of dyskinesia (p < 0.0001, RR = 1.88, 95 % CI 1. 37-2.59) and wearing-off
      phenomenon (p < 0.00001, RR = 1.36, 95 % CI 1. 20-1.55) in patients treated
      initially with L-dopa-sparing therapy compared to L-dopa has been consistently
      reported. What is more, we found more patients on aL-dopa-sparing therapy were
      more than triple as likely to discontinue treatment prematurely due to adverse
      events than L-dopa treatment patients (43.7 vs 15.8 %). L-Dopa alone is the most
      effective medication available for treating the motor symptoms of PD patients,
      despite the greater incidence of involuntary movements. Meanwhile, more patients
      on dopamine agonists or MAOBI were more likely to discontinue treatment
      prematurely than L-dopa alone treatment patients within the long follow-up
      period.

PMID- 25981232
TI  - Functional MRI and calculation processing: considerations on preliminary
      experience about intra-operative validation by electro-stimulation.

PMID- 25981233
TI  - Who prefers to age in place? Cross-sectional survey of middle-aged people in
      Japan.
AB  - AIM: Preference for aging in place among middle-aged people is an important
      element in estimating the future needs for community services of disabled older
      adults. Drawing on Litwak and Longino's typologies of relocation, the present
      study investigated the characteristics of middle-aged adults who prefer to age in
      place and those who prefer to move, at two levels of disability: being unable to
      walk alone and being bedridden. METHODS: In the present cross-sectional study, an
      anonymous, self-administered questionnaire was sent to 2500 community-dwelling
      adults aged 40-64 years. RESULTS: If unable to walk outside alone, 43.0% of
      respondents would prefer to move from their own homes. If bedridden, 29.5%
      preferred to move. After age and sex had been adjusted for, house size, length of
      time living at that house, the number of people living together, and attachment
      to home and neighborhood were independently related to moving preferences if
      unable to walk outside alone. Accessibility of hospitals and supermarkets,
      community participation, and use of the Internet were related to moving
      preferences if bedridden. CONCLUSIONS: Sex, current living arrangement and
      geographic properties are correlated with changes in community-dwelling adults'
      preferences for residential relocation as physical function declines. It is
      necessary for municipal policymakers to understand these correlations in order to
      plan and develop effective community care systems. Geriatr Gerontol Int 2016; 16:
      631-637.

PMID- 25981234
TI  - Extracorporeal shock wave lithotripsy in the primary treatment of encrusted
      ureteral stents.
AB  - Double pigtail (JJ) ureteral stents, are the most commonly used method of urinary
      diversion in the ureteral obstructions. Encrustations may occur as a result of
      prolonged exposure due to forgetting these stents in the body. Removing these
      materials might be an annoyance. Forty-four patients from three tertiary referral
      centres with forgotten JJ stents left in them between the years 2007 and 2014
      were included in the study. Stents could not be removed by attempted cystoscopy.
      As an alternative approach, extracorporeal shock wave lithotripsy (ESWL) was the
      first choice since it is minimally invasive. The results of that treatment are
      presented along with the relevant demographic data. JJ stenting for urolithiasis
      was performed in 36 patients, after open surgery in five patients, and for
      oncological reasons in three patients. ESWL was applied to stents or to any
      suspicious region adjacent to the stent. In 29 of 44 patients, the stents were
      easily removed under cystoscopic procedures while in one patient the fragmented
      residual stent was spontaneously excreted. In eight patients, ureteroscopy was
      required; in five patients, percutaneous nephrolithotripsy was required; and in
      one patient, open surgery was required in order to remove stents. ESWL can be
      considered as a first-line treatment when a forgotten JJ stent is detected
      despite all precautions after any kind of urological intervention involving
      insertion of ureteral stents. 

PMID- 25981237
TI  - The association of J wave and ventricular tachycardia before device implantation
      with device interventions for ventricular tachyarrhythmia.
AB  - BACKGROUND: J wave is known to be associated with increased risk of life
      threatening ventricular arrhythmias in both structural and nonstructural heart
      disease. A documented history of ventricular tachycardia (VT) is also a known
      predictor for future arrhythmic events. The purpose of this study is to
      investigate prognostic factors in ventricular tachyarrhythmias in patients with
      an implanted defibrillator. METHODS: Intracardiac electrograms were thoroughly
      analyzed in patients with either an implanted implantable cardioverter
      defibrillator or with cardiac resynchronization therapy with a defibrillator. The
      relation between the clinical characteristics and the device interventions for
      ventricular tachyarrhythmias was evaluated retrospectively with multivariate Cox
      proportional hazards models. RESULTS: This study enrolled a total of 160 patients
      who were followed for a mean period of 44 +/- 28 months. Of these patients, 31
      (19%) showed J wave and 77 (48%) showed documented VT before the device
      implantation. Multivariate Cox proportional hazards models revealed that the
      presence of J wave and the documented history of VT before the device
      implantation were independently associated with device intervention in patients
      with device implantation even after the adjustment of confounding factors (hazard
      ratio [HR], 2.90; 95% confidence interval [CI], 1.56-5.24; p=0.001 and HR, 4.34;
      95% CI, 2.43-8.05; p<0.0001, respectively). CONCLUSION: The presence of J wave
      and the documented history of VT prior to device implantation served as
      independent predictors of future device intervention for ventricular
      tachyarrhythmias.

PMID- 25981235
TI  - Age-related delay in urinary stone clearance in elderly patients with solitary
      proximal ureteral calculi treated by extracorporeal shock wave lithotripsy.
AB  - We investigated the effects of aging on the stone-free rate (SFR) after shock
      wave lithotripsy (SWL) for the treatment of proximal ureteral calculi. A total of
      247 consecutive patients were retrospectively selected, classified into seven
      groups set at 10 year increments (from 20 to 90 years), and examined for SFR
      after SWL. According to our final analysis, 185 male and 62 female patients with
      an average age of 54.1 years had stones with a diameter of 11.5 mm and a density
      of 893.1 Hounsfield units. On average, SFR was 74.9 % at 3 months after 1.7 SWL
      sessions. SFR gradually reached >= 90 % for each age-group after 1.5-2 years.
      Median durations to achieve 50 % SFR were estimated to be 21 and 86 days for
      those in their 20 and 80 s, respectively. However, the difference between the two
      estimates was not significant (p = 0.064). The durations to achieve 50 % SFR for
      the other groups lay between these two estimates. Aging does not affect long-term
      SFR, but patients aged >= 80 years might experience delayed stone clearance
      within the first 12 months after SWL.

PMID- 25981236
TI  - New or presumably new left bundle branch block in patients with suspected acute
      coronary syndrome: Clinical, echocardiographic, and electrocardiographic features
      from a single-center registry.
AB  - BACKGROUND: In patients with suspected acute coronary syndrome, a new or
      presumably new left bundle branch block (LBBB) does not always imply ST-segment
      elevation myocardial infarction (STEMI). We aimed to show the low frequency of
      STEMI-equivalent in this population and determine the diagnostic value of
      electrocardiographic and echocardiographic features. METHODS: From the 387
      patients captured by the Louisiana State University code STEMI registry between
      2009 and 2012, we examined data on 26 patients with LBBB. These patients were
      divided into 3 groups according to the final diagnosis: (1) STEMI-equivalent,
      defined as an acute coronary occlusion on angiography (2 patients), (2) non-ST
      segment elevation myocardial infarction (4 patients), and (3) diagnoses other
      than myocardial infarction (non-MI) (20 patients). RESULTS: Troponin elevation
      and left ventricular systolic dysfunction were common in all 3 groups (non
      significant p-values). Compared with non-MI patients, patients with STEMI
      equivalent had a larger degree of ST-segment discordance and T-wave discordance,
      as assessed by ST/QRS and T/QRS ratios (p<0.001). ST/QRS ratio >= 0.2 and T/QRS
      ratio >= 0.5 were sensitive and specific for the diagnosis of STEMI-equivalent in
      the setting of LBBB. Conversely, absolute values of ST-segment and T-wave
      discordance were not significantly different between groups. ST-segment
      concordance was highly specific for the diagnosis of STEMI-equivalent, but had a
      limited sensitivity. CONCLUSION: Only a minority of patients with suspected acute
      coronary syndrome and LBBB have a STEMI-equivalent. Excessive relative
      discordance of the ST segment or the T wave appears predictive of STEMI
      equivalent, but this is only hypothesis-generating considering the small
      population size.

PMID- 25981238
TI  - ECG myocardial scar quantification predicts reverse left ventricular remodeling
      and survival after cardiac resynchronization therapy implantation: A
      retrospective pilot study.
AB  - INTRODUCTION: Electrocardiographic (ECG) LV scar quantification may improve
      prediction of CRT response. METHODS AND RESULTS: Data were abstracted in 76
      patients who underwent a first CRT implantation at 2 US centers. Selvester QRS
      scar quantification was performed using the LBBB modified QRS scoring method.
      Seven clinical variables previously associated with reverse LV remodeling (RLVR)
      and QRS score were included in logistic regression analysis. Survival was
      compared across QRS score quartiles using Kaplan-Meier curves. RLVR occurred more
      frequently in patients with QRS score <= 5 (63%) than QRS score>5 (22%),
      (OR=5.83, 95% CI=2.11-16.07). After adjustment for clinical variables using
      logistic regression, QRS score>5 predicted RLVR (Chi-square=20.3, P=0.005,
      AUC=0.782). Patients in the lowest quartile of QRS score (<4) had improved
      survival compared to patients in the other QRS score quartiles (P=0.037).
      CONCLUSION: ECG quantified LV scar predicts RLVR and long-term survival in
      patients with LBBB undergoing CRT implantation.

PMID- 25981239
TI  - Performance of ST and ventricular gradient difference vectors in
      electrocardiographic detection of acute myocardial ischemia.
AB  - INTRODUCTION: Serial analysis could improve ECG diagnosis of myocardial ischemia
      caused by acute coronary occlusion. METHODS: We analyzed ECG pairs of 84 cases
      and 398 controls. In case-patients, who underwent elective percutaneous coronary
      intervention, ischemic ECGs during balloon occlusion were compared with preceding
      non-ischemic ECGs. In control-patients, two elective non-ischemic ECGs were
      compared. In each ECG the ST vector at the J point and the ventricular gradient
      (VG) vector was computed, after which difference vectors DeltaST and DeltaVG were
      computed within patients. Finally, receiver operating characteristic analysis was
      done. RESULTS: Areas under the curve were 0.906 (P<0.001; CI 0.862-0.949; SE
      0.022) for DeltaST and 0.880 (P<0.001; CI 0.833-0.926; SE 0.024) for DeltaVG.
      Sensitivity and specificity of conventional ST-elevation myocardial infarction
      (STEMI) criteria were 70.2% and 89.1%, respectively. At matched serial analysis
      specificity and STEMI specificity, serial analysis sensitivity was 78.6% for
      DeltaST and 71.4% for DeltaVG (not significantly different from STEMI
      sensitivity). At matched serial analysis sensitivity and STEMI sensitivity,
      serial analysis specificity was 96.5% for DeltaST and 89.3% for DeltaVG; DeltaST
      and STEMI specificities differed significantly (P<0.001). CONCLUSION: Detection
      of acute myocardial ischemia by serial ECG analysis of ST and VG vectors has
      equal or even superior performance than the STEMI criteria. This concept should
      be further evaluated in triage ECGs of patients suspected from having acute
      myocardial ischemia.

PMID- 25981240
TI  - Understanding compassion fatigue: understanding compassion.
AB  - AIM: A discussion of how the construct of compassion fatigue is understood in
      nursing. BACKGROUND: Compassion fatigue is a topic commonly found in nursing
      literature. DESIGN: Discussion paper. DATA SOURCES: The literature from 1992-2012
      on compassion fatigue was examined. The literature from 1998-2012 on compassion
      was examined. IMPLICATIONS FOR NURSING: There are multiple and diverse
      understandings and definitions of what compassion fatigue is. So much so, there
      are equally multiple, diverse and conflicting strategies to mitigate it. To
      understand better what compassion fatigue is, an examination of what compassion
      is was undertaken. Much is written that nurses are, or should be compassionate.
      Compassion is an archetype of nursing. However, there is little in the nursing
      literature defining what compassion is. Literature on compassion outside of
      nursing was then examined. There is a growing body of theory and research about
      compassion in other disciplines. None of the multiple definitions of nurse
      compassion fatigue match this understanding of compassion. The tools most often
      used to measure nurse compassion fatigue do not appear to measure the construct
      of compassion. CONCLUSION: To understand what nurse compassion fatigue is, we
      must first understand what nurse compassion is.

PMID- 25981242
TI  - Detection of the Bacterial Potato Pathogens Pectobacterium and Dickeya spp. Using
      Conventional and Real-Time PCR.
AB  - Blackleg and soft rot of potato, caused by Pectobacterium and Dickeya spp., are
      major production constraints in many potato-growing regions of the world. Despite
      advances in our understanding of the causative organisms, disease epidemiology,
      and control, blackleg remains the principal cause of down-grading and rejection
      of potato seed in classification schemes across Northern Europe and many other
      parts of the world. Although symptom recognition is relatively straightforward
      and is applied universally in seed classification schemes, attributing disease to
      a specific organism is problematic and can only be achieved through the use of
      diagnostics. Similarly as disease spread is largely through the movement of
      asymptomatically infected seed tubers and, possibly in the case of Dickeya spp.,
      irrigation waters, accurate and sensitive diagnostics are a prerequisite for
      detection. This chapter describes the diagnostic pathway that can be applied to
      identify the principal potato pathogens within the genera Pectobacterium and
      Dickeya. 

PMID- 25981241
TI  - In virio SHAPE analysis of tRNA(Lys3) annealing to HIV-1 genomic RNA in wild type
      and protease-deficient virus.
AB  - BACKGROUND: tRNA(Lys3) annealing to the viral RNA of human immunodeficiency virus
      type-1 (HIV-1) is an essential step in the virus life cycle, because this tRNA
      serves as the primer for initiating reverse transcription. tRNA(Lys3) annealing
      to viral RNA occurs in two steps. First, Gag promotes annealing of tRNA(Lys3) to
      the viral RNA during cytoplasmic HIV-1 assembly. Second, mature nucleocapsid
      (NCp7), produced from the processing of Gag by viral protease during viral
      budding from the cell, remodels the annealed complex to form a more stable
      interaction between the viral RNA and tRNA(Lys3), resulting in a more tightly
      bound and efficient primer for reverse transcription. RESULTS: In this report, we
      have used in virio SHAPE analysis of both the 5'-untranslated region in HIV-1 RNA
      and the annealed tRNA(Lys3) to determine structural differences of the annealed
      complex that occur between protease-negative (Pr-) and wild type viruses. Our
      results indicate that the weaker binding of tRNA(Lys3) annealed by Gag in Pr-
      virions reflects both missing interactions of tRNA(Lys3) with viral RNA regions
      in the upper PBS stem, and a weaker interaction with the internal stem-loop found
      within the unannealed primer binding site in viral RNA. CONCLUSIONS: We propose
      secondary structure models for the tRNA(Lys3)/viral RNA annealed complexes in PR-
      and wild type viruses that support the two-step annealing model by showing that
      Gag promotes a partial annealing of tRNA(Lys3) to HIV-1 viral RNA, followed by a
      more complete annealing by NCp7.

PMID- 25981243
TI  - Detection and identification of Phoma pathogens of potato.
AB  - Phoma foveata, Phoma exigua var. exigua, and Phoma eupyrena are fungal pathogens
      of potato, causing gangrene or pit rot symptoms in tubers, and they are
      responsible for significant crop losses. Various techniques are available to
      identify these pathogens in the laboratory. A multiplex Plexor((r)) real-time PCR
      method which can detect and identify these pathogens in a single reaction will be
      presented. 

PMID- 25981244
TI  - Diagnosis of Ramularia collo-cygni and Rhynchosporium spp. in Barley.
AB  - Ramularia leaf spot and Rhynchosporium leaf scald are two of the major diseases
      of barley crops in cooler temperate countries. The methods below are aimed at the
      identification and quantification of fungal DNA in leaf samples but can also be
      used for pathogen detection from seed or DNA extracted from environmental
      samplers. The methods describe in detail two individual quantitative PCR tests.
      The successful multiplexing of assays will lead to faster throughput of samples. 

PMID- 25981245
TI  - A real-time multiplex PCR assay used in the identification of closely related
      fungal pathogens at the species level.
AB  - The advent of real-time PCR and new chemistries such as TaqManTM and SYBRTMgreen
      has been used in plant pathology to aid in the identification of fungal,
      bacterial and viral pathogens. These chemistries have provided another tool to be
      used in the identification of fungal pathogens that are hard to differentiate on
      the basis of morphology. This work describes an assay that was developed to
      identify five different species of the pathogen Tilletia that causes smuts and
      bunts in cereals. 

PMID- 25981246
TI  - Diagnostics of Tree Diseases Caused by Phytophthora austrocedri Species.
AB  - We present methods for the detection and quantification of four Phytophthora
      species which are pathogenic on trees; Phytophthora ramorum, Phytophthora
      kernoviae, Phytophthora lateralis, and Phytophthora austrocedri. Nucleic acid
      extraction methods are presented for phloem tissue from trees, soil, and pure
      cultures on agar plates. Real-time PCR methods are presented and include primer
      and probe sets for each species, general advice on real-time PCR setup and data
      analysis. A method for sequence-based identification, useful for pure cultures,
      is also included. 

PMID- 25981247
TI  - Real-Time LAMP for Chalara fraxinea Diagnosis.
AB  - Chalara fraxinea is the causal agent of ash dieback, a disease affecting Fraxinus
      excelsior and F. angustifolia across Europe. Loop-mediated isothermal
      amplification (LAMP) is a rapid, DNA-based method which can be used for specific
      detection of plant pathogens in infected material. The combination of a rapid
      LAMP assay for C. fraxinea with a simple sample preparation method in a user
      friendly kit format raises the potential for testing to be carried out away from
      conventional laboratory facilities, to expedite measure to manage this damaging
      disease. 

PMID- 25981248
TI  - Loop-Mediated Isothermal Amplification Procedure (LAMP) for Detection of the
      Potato Zebra Chip Pathogen "Candidatus Liberibacter solanacearum".
AB  - An efficient loop-mediated isothermal amplification procedure (LAMP) for the
      detection of "Candidatus Liberibacter solanacearum" (Lso), the bacterial causal
      agent of potato zebra chip (ZC) disease, is described in this chapter. Similar to
      the polymerase chain reaction (PCR), the LAMP employs a bacterial polymerase to
      amplify specific DNA sequences. However, the method differs from conventional PCR
      in that it uses six primers specific to the target region to generate a loop
      structure and autocycling strand displacement rather than thermocycling for
      sequence amplification. Moreover, unlike PCR that requires agarose gel
      electrophoresis for resolution, the positive LAMP results can be visualized
      directly as a precipitate within the reaction tubes. The 16S rDNA gene of "Ca.
      Liberibacter solanacearum" was used as the target for the design of the six LAMP
      primers. The LAMP technique is a reliable, rapid, and cost-effective method of
      detecting the "Ca. Liberibacter solanacearum" pathogen in the potato/tomato
      psyllid, Bactericera cockerelli, and in field-grown potato plants and tubers. 

PMID- 25981249
TI  - Loop-Mediated Isothermal Amplification (LAMP) for Detection of Phytoplasmas in
      the Field.
AB  - Loop-mediated isothermal amplification (LAMP) is a nucleic acid-based detection
      method with many applications. This chapter details its use for detection of
      phytoplasma diseases, combining a rapid 2-min DNA extraction method with real
      time LAMP product detection such that the entire procedure can be undertaken and
      completed in the field within 40 min. Furthermore, the assays include an anneal
      curve validation step to guard against false positives and an assay for host
      plant DNA to guard against false negatives. 

PMID- 25981250
TI  - Diagnosis of Phytoplasmas by Real-Time PCR Using Locked Nucleic Acid (LNA)
      Probes.
AB  - Phytoplasma infections are regularly reported worldwide, and concerns about their
      threats on agricultural production, especially in relation to global climate
      change, are increasing. Sensitive and reliable detection methods are important to
      ensure that propagation material is free of phytoplasma infection and for
      epidemiological studies that may provide information to limit the extent of
      phytoplasma diseases and to prevent large-scale crop losses. The detection method
      described here uses LNA chemistry in real-time PCR. It has been developed and
      validated for use on potatoes, and its sensitivity and specificity make it
      suitable for use in postentry potato quarantine and initiation of potato nuclear
      stocks to ensure that material is phytoplasma-free. 

PMID- 25981251
TI  - Q-bank phytoplasma: a DNA barcoding tool for phytoplasma identification.
AB  - DNA barcoding is an identification method based on comparison of a short DNA
      sequence with known sequences from a database. A DNA barcoding tool has been
      developed for phytoplasma identification. This phytoplasma DNA barcoding protocol
      based on the tuf gene has been shown to identify phytoplasmas belonging to the
      following groups: 16SrI, 16SrII, 16SrIII, 16SrIV, 16SrV, 16SrVI, 16SrVII, 16SrIX,
      16SrX, 16SrXI, 16SrXII, 16SrXIV, 16SrXX, and 16SrXXI. 

PMID- 25981252
TI  - High-throughput diagnosis of potato cyst nematodes in soil samples.
AB  - Potato cyst nematode (PCN) is a damaging soilborne pest of potatoes which can
      cause major crop losses. In 2010, a new European Union directive (2007/33/EC) on
      the control of PCN came into force. Under the new directive, seed potatoes can
      only be planted on land which has been found to be free from PCN infestation
      following an official soil test. A major consequence of the new directive was the
      introduction of a new harmonized soil sampling rate resulting in a threefold
      increase in the number of samples requiring testing. To manage this increase with
      the same staffing resources, we have replaced the traditional diagnostic methods.
      A system has been developed for the processing of soil samples, extraction of DNA
      from float material, and detection of PCN by high-throughput real-time PCR.
      Approximately 17,000 samples are analyzed each year using this method. This
      chapter describes the high-throughput processes for the production of float
      material from soil samples, DNA extraction from the entire float, and subsequent
      detection and identification of PCN within these samples. 

PMID- 25981253
TI  - Detection of Nepovirus Vector and Nonvector Xiphinema Species in Grapevine.
AB  - Fanleaf degeneration is considered the most damaging viral disease of grapevine.
      The two major nepoviruses involved are Grapevine fanleaf virus (GFLV) and Arabis
      mosaic virus (ArMV) which are respectively and specifically transmitted by the
      dagger nematodes Xiphinema index and X. diversicaudatum. The methods described
      below are aimed at detecting four prevalent grapevine Xiphinema species: the
      vector species previously mentioned and two nonvector species X. vuittenezi and
      X. italiae. 

PMID- 25981254
TI  - Molecular and serological methods for the diagnosis of viruses in potato tubers.
AB  - Viruses cause important diseases to potato crops. Monitoring virus content in
      plant material for quarantine or seed certification scheme purposes is essential
      to prevent the spread of viruses and to minimize the impact of viral diseases.
      There are currently two main methods for virus diagnosis in potato tubers:
      growing-on ELISA testing which requires breaking tuber dormancy followed by an
      ELISA test on grown plantlets and direct real-time RT-PCR testing on tubers. This
      chapter will describe both methods that can be adapted for large-scale virus
      testing activities. 

PMID- 25981255
TI  - Immunocapture-Multiplex RT-PCR for the Simultaneous Detection and Identification
      of Plant Viruses and Their Strains: Study Case, Potato Virus Y (PVY).
AB  - Immunocapture-reverse transcription-polymerase chain reaction (IC-RT-PCR) is a
      sensitive, reproducible, and robust method for the detection and identification
      of RNA viruses. The IC step provides a simple method to isolate virus particles
      from plant tissue, particularly when inhibitory substances are present, and thus
      enables subsequent use of RT-PCR amplification for large-scale virus testing and
      typing. The multiplex format of the PCR is often used for the detection and
      identification of multiple virus/strain simultaneously to save time, labor, and
      cost. Potato virus Y (PVY) is one of the most economically important viruses
      infecting potato worldwide. PVY exists as a complex of at least nine strains and
      many more unclassified recombinants that vary in their genome structures,
      phenotypes, and their economic importance. In the current chapter, a detailed
      protocol of an IC-based, multiplex RT-PCR assay for the detection and
      identification of various PVY strains is described. 

PMID- 25981256
TI  - SNaPshot and CE-SSCP: Two Simple and Cost-Effective Methods to Reveal Genetic
      Variability Within a Virus Species.
AB  - The multiplex SNaPshot and the capillary electrophoresis-single-strand
      conformation polymorphism (CE-SSCP) procedures are here used for rapid and high
      throughput description of the molecular variability of viral populations. Both
      approaches are based on (1) standard amplification of genomic sequence(s), (2)
      labeled primers or labeled single-stranded DNA, and (3) migration of fluorescent
      labeled molecules in capillary electrophoresis system. The SNaPshot technology
      was used to describe the diversity of 20 targeted single nucleotide polymorphisms
      (SNPs) selected from alignment of viral genomic sequences retrieved from public
      database. The CE-SSCP procedure was applied to identify the polymorphisms of two
      small (<500 bases in length) genomic regions of viral genomes. The different
      steps of SNaPshot and CE-SSCP setup procedures are presented using Potato virus Y
      (PVY, Potyvirus) and Plum pox virus (PPV, Potyvirus) RNA viruses as molecular
      targets, respectively. 

PMID- 25981257
TI  - Detection and Characterization of Viral Species/Subspecies Using Isothermal
      Recombinase Polymerase Amplification (RPA) Assays.
AB  - Numerous molecular-based detection protocols include an amplification step of the
      targeted nucleic acids. This step is important to reach the expected sensitive
      detection of pathogens in diagnostic procedures. Amplifications of nucleic acid
      sequences are generally performed, in the presence of appropriate primers, using
      thermocyclers. However, the time requested to amplify molecular targets and the
      cost of the thermocycler machines could impair the use of these methods in
      routine diagnostics. Recombinase polymerase amplification (RPA) technique allows
      rapid (short-term incubation of sample and primers in an enzymatic mixture) and
      simple (isothermal) amplification of molecular targets. RPA protocol requires
      only basic molecular steps such as extraction procedures and agarose gel
      electrophoresis. Thus, RPA can be considered as an interesting alternative to
      standard molecular-based diagnostic tools. In this paper, the complete procedures
      to set up an RPA assay, applied to detection of RNA (Potato virus Y, Potyvirus)
      and DNA (Wheat dwarf virus, Mastrevirus) viruses, are described. The proposed
      procedure allows developing species- or subspecies-specific detection assay. 

PMID- 25981258
TI  - Virus testing by PCR and RT-PCR amplification in berry fruit.
AB  - Berry fruit crops are prone to infection by a wide range of viruses, with the
      list expanding every year, primarily because of the expansion of the crops to new
      geographic regions. Although some methods allow for virus detection in a
      nonspecific manner, the advent of cheap and effective nucleic acid sequencing
      technologies has allowed for the development of species-specific tests. This
      chapter describes methods for extraction of nucleic acids for molecular testing
      from a range of different berry fruit crops and lists oligonucleotide primers
      that have been developed for amplification of a large number of berry fruit
      viruses. 

PMID- 25981260
TI  - Detection of Potato spindle tuber viroid and Other Related Viroids by a DIG
      Labelled RNA Probe.
AB  - Viroids can cause diseases of considerable economic importance; in Europe the
      main concern is with pospiviroids that may affect the tomato and potato
      industries. Methods for detection are required that are both sensitive and
      robust. The detection method described here is a probe hybridization method with
      a commercially available digoxigenin (DIG) labelled full-length Potato spindle
      tuber viroid (PSTVd) RNA probe. This method detects PSTVd and all other known
      pospiviroids. 

PMID- 25981259
TI  - Metagenomics Approaches Based on Virion-Associated Nucleic Acids (VANA): An
      Innovative Tool for Assessing Without A Priori Viral Diversity of Plants.
AB  - This chapter describes an efficient approach that combines quality and yield
      extraction of viral nucleic acids from plants containing high levels of secondary
      metabolites and a sequence-independent amplification procedure for both the
      inventory of known plant viruses and the discovery of unknown ones. This approach
      turns out to be a useful tool for assessing the virome (the genome of all the
      viruses that inhabit a particular organism) of plants of interest. We here show
      that this approach enables the identification of a novel Potyvirus member within
      a single plant already known to be infected by two other Potyvirus species. 

PMID- 25981261
TI  - Microarray platform for the detection of a range of plant viruses and viroids.
AB  - Diagnostic microarrays are a useful tool for the simultaneous detection of
      multiple targets. In this chapter we describe the use of a simple tube-based
      microarray platform for the detection of plant infecting viruses and viroids. 

PMID- 25981262
TI  - Multiplex detection of plant pathogens through the Luminex MagPlex bead system.
AB  - Here we describe a versatile multiplex method for both the serological and
      molecular detection of plant pathogens. The Luminex MagPlex bead system uses
      small paramagnetic microspheres ("beads"), either coated with specific antibodies
      or oligonucleotides, which capture respectively viruses and/or bacteria or PCR
      products obtained from their genetic material. The Luminex MagPlex bead system
      allows true multiplex detection of up to 500 targets in a single sample on a
      routine basis. The liquid suspension nature of the method significantly improves
      (1) assay speed, (2) detection limits and (3) dynamic range. It can also
      considerably reduce labor and consumables costs.

PMID- 25981263
TI  - Next-generation sequencing of elite berry germplasm and data analysis using a
      bioinformatics pipeline for virus detection and discovery.
AB  - Berry crops (members of the genera Fragaria, Ribes, Rubus, Sambucus, and
      Vaccinium) are known hosts for more than 70 viruses and new ones are identified
      continually. In modern berry cultivars, viruses tend to be asymptomatic in single
      infections and symptoms only develop after plants accumulate multiple viruses.
      Most certification programs are based on visual observations. Infected,
      asymptomatic material may be propagated in the nursery system and shipped to
      farms where plants acquire additional viruses and develop symptoms. This practice
      may result in disease epidemics with great impact to producers and the natural
      ecosystem alike. In this chapter we present work that allows for the detection of
      known and discovery of new viruses in elite germplasm, having the potential to
      greatly reduce virus dispersal associated with movement of propagation material. 

PMID- 25981264
TI  - Metagenomic next-generation sequencing of viruses infecting grapevines.
AB  - Next-generation sequencing (NGS) technologies, for the first time, provide a
      truly "complete" representation of the viral (and other) pathogens present in a
      host organism. This is achieved in an unbiased way, and without any prior
      biological or molecular knowledge of these pathogen(s). During recent years a
      number of broad approaches, for most of the popular NGS platforms, have been
      developed. Here we describe such a protocol-one that accurately and reliably
      analyze viruses (and viroids) infecting grapevine. Our strategy relies on the
      synthesis of cDNA sequencing libraries from dsRNA, extracted from diseased
      grapevine tissues; the sequencing of these on an Illumina platform, and a
      streamlined bioinformatics pipeline to analyze the NGS data, yielding the virus
      composition (virome) of a specific grapevine tissue type, organ, entire plant, or
      even a vineyard. 

PMID- 25981265
TI  - Droplet digital PCR for absolute quantification of pathogens.
AB  - The recent advent of different digital PCR (dPCR) platforms is enabling the
      expansion of this technology for research and diagnostic applications worldwide.
      The main principle of dPCR, as in other PCR-based methods including quantitative
      PCR (qPCR), is the specific amplification of a nucleic acid target. The
      distinctive feature of dPCR is the separation of the reaction mixture into
      thousands to millions of partitions which is followed by a real time or end point
      detection of the amplification. The distribution of target sequences into
      partitions is described by the Poisson distribution, thus allowing accurate and
      absolute quantification of the target from the ratio of positive against all
      partitions at the end of the reaction. This omits the need to use reference
      materials with known target concentrations and increases the accuracy of
      quantification at low target concentrations compared to qPCR. dPCR has also shown
      higher resilience to inhibitors in a number of different types of samples. In
      this chapter we describe the droplet digital PCR (ddPCR) workflow for the
      detection and quantification of pathogens using the droplet digital Bio-Rad
      platform QX100. We present as an example the quantification of the quarantine
      plant pathogenic bacterium, Erwinia amylovora. 

PMID- 25981266
TI  - Making ethical decisions: stories from surgeons.
AB  - Surgeons share their challenges and dilemmas in making ethical decisions in these
      twelve personal stories. The three commentary articles draw out the lessons the
      stories address. The commentators come from diverse backgrounds including
      sociology, bioethics, nursing, and surgery. 

PMID- 25981267
TI  - Patient vs. self in surgical practice.

PMID- 25981268
TI  - Consenting for novel and dangerous surgical procedures with minimal supporting
      evidence.

PMID- 25981269
TI  - May of 1973.

PMID- 25981270
TI  - Death perception: how temporary ventilator disconnection helped my family accept
      brain death and donate organs.

PMID- 25981271
TI  - Operating in a contemporary safety net.

PMID- 25981272
TI  - I am not sure?

PMID- 25981273
TI  - Whisper before you go.

PMID- 25981274
TI  - From impatience to empathy.

PMID- 25981275
TI  - Operating through hatred.

PMID- 25981276
TI  - "Just because you can--doesn't mean you should".

PMID- 25981277
TI  - Immortalization: placement of a percutaneous endoscopic gastrostomy tube and
      tracheostomy in a neurologically devastated patient.

PMID- 25981278
TI  - Care of the terminal patient: Are we on the same page?

PMID- 25981279
TI  - Deciphering the surgeons' stories.
AB  - Twelve narratives written by surgeons on ethical decision-making are analyzed in
      this commentary. Several major themes in their narratives are discussed: the
      preponderance of end-of-life issues; the struggle to be inclusively empathetic,
      even under emotionally alienating circumstances; social justice; and the
      disagreement among colleagues about how to deal with patients in situations of
      medical uncertainty. The commentary not only discusses the areas of stress that
      the surgeons identify in their accounts. It also highlights phenomena and themes
      that are missing from them, and calls for more work to be done gathering stories
      from surgeons to explore and explain the "gaps" in this narrative collection. 

PMID- 25981280
TI  - Surgical medicine: imperfect and extraordinary.
AB  - The themes that emerge from these rich narratives by surgeons are familiar ones
      in the experiences of diverse health care providers. Questions about and
      difficulties with communication and with informed consent are common and
      troubling. Uncertainty was also a prevalent theme in these stories, uncertainty
      about the right thing to do or say and about how to treat the patients and
      families the surgeons wrote about. Uncertainty is a reality in medicine, and it
      is often said that medicine is an art, not just a science. Although in medicine
      it is uncommon to find a situation so black and white that the course of action
      is obvious, this may be less true in surgery. Surgeons are prototypically
      confident in their recommendations. Yet, these surgeons poignantly describe
      uncertainty. Sometimes the uncertainty leads to careful reflection, taking a
      stand, or changing practice, and sometimes it lead to moral distress. 

PMID- 25981281
TI  - Surgical ethics: surgical virtue and more.
AB  - The encounter between a patient and her surgeon is unique for several reasons.
      The surgeon inflicts pain upon a patient for the patient's own good. An operative
      intervention is irreducibly personal, such that the decisions about and
      performance of operations are inseparable from the idiosyncrasies of the
      individual surgeon. Furthermore, there is a chasm of knowledge between the
      patient and surgeon that is difficult to cross. Hence, training in the discipline
      of surgery includes the inculcation of certain virtues and practices to safeguard
      against abuses of this relationship and to make sure that the best interests of
      the patient are prioritized. The stories in this issue are evidence that in
      contemporary practice this is not quite enough, as surgeons reflect on instances
      they felt were ethically challenging. Common themes include the difficulty in
      communicating surgical uncertainty, patient-surgeon relationships, ethical issues
      in surgical training, and the impact of the technological imperative on caring
      for dying patients. 

PMID- 25981282
TI  - Confidentiality, informed consent, and children's participation in research
      involving stored tissue samples: interviews with medical professionals from the
      Middle East.
AB  - Ethical issues regarding research biobanks continue to be a topic of intense
      debate, especially issues of confidentiality, informed consent, and child
      participation. Although considerable empirical literature concerning research
      biobank ethics exists, very little information is available regarding the
      opinions of medical professionals doing genetics research from the Middle East,
      especially Arabic speaking countries. Ethical guidelines for research biobanks
      are critically needed as some countries in the Middle East are starting to
      establish national research biobanks. Islam is the dominant religion in these
      countries, and it affects people's behavior and influences their positions.
      Moreover, communities in these countries enjoy a set of customs, traditions and
      social norms, and have social and familial structures that must be taken into
      account when developing research policies. We interviewed 12 medical
      professionals from the Middle East currently working with stored tissue samples
      to document their opinions. We found general agreement. Participants' primary
      concerns were similar to the views of researchers internationally. Since children
      tend to represent a high percentage of Middle Eastern populations, and because
      children's bodies are not just small adult bodies, the interviewed professionals
      strongly believed that it is imperative to include children in biobank research.
      Participants generally believed that protecting confidentiality is socially very
      important and that informed consent/assent must be obtained from both adult and
      child participants. This study provides a starting point for additional studies. 

PMID- 25981283
TI  - Caregivers' role in maternal-fetal conflict.
AB  - The case, which occurred in a public hospital in Turkey in 2005, exhibits a
      striking dilemma between a mother's and her fetus' interests. For a number of
      reasons, the mother refused to cooperate with the midwives and obstetrician in
      the process of giving birth, and wanted to leave the hospital. The care providers
      evaluated the case as a matter of maternal autonomy and asked the mother to give
      her consent to be discharged from the hospital, which she did despite the fact
      that her cervix was fully open. She left the hospital and gave birth shortly
      thereafter. Subsequently, the baby died two days later. In light of the
      contemporary ethical principles, the mother's competency could be debatable due
      to the physical and psychological conditions the mother confronted. Furthermore,
      protection of the fetus' life should have been taken into account by the
      caregivers when making a decision concerning discharging of the mother. 

PMID- 25981284
TI  - Physician, know thyself: the role of reflection in bioethics and professionalism
      education.
AB  - Reflection in medical education is becoming more widespread. Drawing on our
      Jesuit Catholic heritage, the Loyola University Chicago Stritch School of
      Medicine incorporates reflection in its formal curriculum and co-curricular
      programs. The aim of this type of reflection is to help students in their
      formation as they learn to step back and analyze their experiences in medical
      education and their impact on the student. Although reflection is incorporated
      through all four years of our undergraduate medical curriculum, this essay will
      focus on three areas where bioethics faculty and medical educators have
      purposefully integrated reflection in the medical school, specifically within our
      bioethics education and professional development efforts: 1) in our three-year
      longitudinal clinical skills course Patient Centered Medicine (PCM), 2) in our co
      curricular Bioethics and Professionalism Honors Program, and 3) in our newly
      created Physician's Vocation Program (PVP). 

PMID- 25981285
TI  - The practice of surgery.

PMID- 25981288
TI  - Screening of epidermal growth factor receptor inhibitors in natural products by
      capillary electrophoresis combined with high performance liquid chromatography
      tandem mass spectrometry.
AB  - A method for screening of inhibitors to epidermal growth factor receptor (EGFR)
      in natural product extracts with capillary electrophoresis (CE) in conjunction
      with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      is reported. The method was established by employing 5-carboxyfluorescein labeled
      substrate peptide, two commercially available EGFR inhibitors OSI-744 and ZD1839,
      and a small chemical library consisted of 39 natural product extracts derived
      from the Traditional Chinese Medicines. Biochemical assay of crude natural
      product extracts was carried out by using CE equipped with a laser induced
      fluorescence detector. The CE separation allowed an accurately quantitative
      measurement of the phosphorylated product, hence the measurement of the enzymatic
      activity as well as the inhibition kinetics. The hits are identified if the peak
      area of the phosphorylated product is reduced in comparison with the negative
      control. The active constituents in the natural product extract were then
      identified by an assay-guided isolation with HPLC-MS/MS system. With the method,
      the flavonoids component of the Lycopus lucidus extract, namely quercetin and
      rutin were identified to be the active ingredients. Their IC50 values were
      determined as 0.88 MUM and 10.1 MUM, respectively. This result demonstrated a
      significant merit of our method in the identification of the bioactive compounds
      in natural products.

PMID- 25981287
TI  - Imidazolium embedded C8 based stationary phase for simultaneous reversed
      phase/hydrophilic interaction mixed-mode chromatography.
AB  - A new imidazolium embedded C8 based stationary phase (SIL-MPS-VOL) was facilely
      prepared by two steps and characterized by Fourier transform infrared
      spectrometry and thermogravimetric analysis. Due to the introduction of
      quaternary imidazolium group to the traditional C8 stationary phase, the
      developed SIL-MPS-VOL column demonstrated both reversed-phase liquid
      chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC)
      retention mechanisms. A series of hydrophobic and hydrophilic test samples,
      including benzene homologues, anilines, positional isomers, nucleosides and
      nucleotides, were used to evaluate the developed SIL-MPS-VOL stationary phase. A
      rapid separation time, high separation efficiency and planar selectivity were
      achieved, compared with the commercially available C8 column. Moreover, the
      developed stationary phase was further used to detect and separate of melamine in
      powdered infant formula and high polar component of secondary metabolites of
      Trichoderma, and improved separation efficiency was achieved, indicating the
      potential merits of the developed SIL-MPS-VOL stationary phase for simultaneous
      separation of complex hydrophobic and hydrophilic samples with high selectivity. 

PMID- 25981289
TI  - Binding of angiogenesis inhibitor kringle 5 to its specific ligands by frontal
      affinity chromatography.
AB  - The interactions between angiogenesis inhibitor Kringle 5 and its five specific
      ligands were investigated by frontal affinity chromatography in combination with
      fluorescence spectra and site-directed molecular docking. The binding constants
      of trans-4-(aminomethyl) cyclohexane carboxylic acid (AMCHA), epsilon
      aminocaproic acid (EACA), benzylamine, 7-aminoheptanoic acid (7-AHA) and L-lysine
      to Kringle 5 were 19.0*10(3), 7.97*10(3), 6.45*10(3), 6.07*10(3) and 4.04*10(3)
      L/mol, respectively. The five ligands bound to Kringle 5 on the lysine binding
      site in equimolar amounts, which was pushed mainly by hydrogen bond and Van der
      Waals force. This binding affinity was believed to be dependent on the functional
      group and flexible feature in ligands. This study will provide an important
      insight into the binding mechanism of angiogenesis inhibitor Kringle 5 to its
      specific ligands.

PMID- 25981290
TI  - Determination of caffeoylquinic acids in feed and related products by focused
      ultrasound solid-liquid extraction and ultra-high performance liquid
      chromatography-mass spectrometry.
AB  - A method to determine caffeoylquinic acids (CQAs) in three sources (herbal
      extract, feed additive and finished feed) using for the first time focused
      ultrasound solid-liquid extraction (FUSLE) followed by ultra-high performance
      liquid chromatography (UPLC) coupled to quadrupole-time of flight mass
      spectrometry is presented. Pressurized liquid extraction (PLE) was also tested as
      extraction technique but it was discarded because cynarin was not stable under
      temperature values used in PLE. The separation of the CQAs isomers was carried
      out in only seven minutes. FUSLE variables such as extraction solvent, power and
      time were optimized by a central composite design. Under optimal conditions,
      FUSLE extraction was performed with 8mL of an 83:17 methanol-water mixture for
      30s at a power of 60%. Only two extraction steps were found necessary to recover
      analytes quantitatively. Sensitivity, linearity, accuracy and precision were
      established. Matrix effect was studied for each type of sample. It was not
      detected for mono-CQAs, whereas the cynarin signal was strongly decreased due to
      ionization suppression in presence of matrix components; so the quantification by
      standard addition was mandatory for the determination of di-caffeoylquinic acids.
      Finally, the method was applied to the analysis of herbal extracts, feed
      additives and finished feed. In all samples, chlorogenic acid was the predominant
      CQA, followed by criptochlorogenic acid, neochlorogenic acid and cynarin. The
      method allows an efficient determination of chlorogenic acid with good recovery
      rates. Therefore, it may be used for screening of raw material and for process
      and quality control in feed manufacture. 

PMID- 25981292
TI  - Burns in sub-Saharan Africa: A review.
AB  - OBJECTIVE: Burns are important preventable causes of morbidity and mortality,
      with a disproportionate incidence in sub-Saharan Africa. The management of these
      injuries in sub-Saharan Africa is a challenge because of multiple other competing
      problems such as infectious diseases (HIV/AIDS, tuberculosis and malaria),
      terrorist acts and political instability. There is little investment in
      preventive measures, pre-hospital, in-hospital and post-discharge care of burns,
      resulting in high numbers of burns, high morbidity and mortality. Lack of data
      that can be used in legislation and policy formulation is a major hindrance in
      highlighting the problem of burns in this sub-region. METHODS: An online search
      of publications on burns from sub-Saharan countries was performed. RESULTS: A
      total of 54 publications with 32,862 patients from 14 countries qualified for
      inclusion in the study. The average age was 15.3 years. Children aged 10 years
      and below represented over 80% of the burn patient population. Males constituted
      55% of those who suffered burns. Scalds were the commonest cause of thermal
      injuries, accounting for 59% of all burns, while flame burns accounted for 33%.
      The burn mortality averaged 17%, or the death of one of every five burn victims.
      CONCLUSIONS: These statistics indicate the need for an urgent review of burn
      policies and related legislation across the sub-Saharan region to help reduce
      burns, and provide a safe environment for children.

PMID- 25981291
TI  - Development of enhanced capacity affinity microcolumns by using a hybrid of
      protein cross-linking/modification and immobilization.
AB  - A hybrid method was examined for increasing the binding capacity and activity of
      protein-based affinity columns by using a combination of protein cross
      linking/modification and covalent immobilization. Various applications of this
      approach in the study of drug-protein interactions and in use with affinity
      microcolumns were considered. Human serum albumin (HSA) was utilized as a model
      protein for this work. Bismaleimidohexane (BMH, a homobifunctional maleimide) was
      used to modify and/or cross-link HSA through the single free sulfhydryl group
      that is present on this protein. Up to a 75-113% increase in protein content was
      obtained when comparing affinity supports that were prepared with BMH versus
      reference supports that were made by using only covalent immobilization. Several
      drugs that are known to bind HSA (e.g., warfarin, verapamil and carbamazepine)
      were further found to have a significant increase in retention on HSA
      microcolumns that were treated with BMH (i.e., a 70-100% increase in protein
      based retention). These BMH-treated HSA microcolumns were used in chiral
      separations and in ultrafast affinity extraction to measure free drug fractions
      in drug/protein mixtures, with the latter method giving association equilibrium
      constants that had good agreement with literature values. In addition, it was
      found that the reversible binding of HSA with ethacrynic acid, an agent that can
      combine irreversibly with the free sulfhydryl group on this protein, could be
      examined by using the BMH-treated HSA microcolumns. The same hybrid
      immobilization method could be extended to other proteins or alternative
      applications that may require protein-based affinity columns with enhanced
      binding capacities and activities. 

PMID- 25981293
TI  - Role of angiotensin-converting enzyme (ACE) and ACE2 in a rat model of smoke
      inhalation induced acute respiratory distress syndrome.
AB  - Smoke inhalation induced acute respiratory distress syndrome (ARDS) has become
      more and more common throughout the world and it is hard to improve the outcome.
      The present research was to investigate possible roles of angiotensin-converting
      enzyme (ACE) and ACE2 in lung injury resulted from smoke exposure. Rats were
      exposed to dense smoke to induce ARDS. Histological changes, blood gases,
      bronchoalveolar lavage fluids (BALF) and wet-to-dry weight were analyzed to
      evaluate lung injury after smoke inhalation; beside, we also measured the
      expression of ACE and ACE2 at different time points to explore the possible
      mechanism of those changes. The results showed that pH of arterial blood, partial
      blood oxygen (PaO2) and blood oxygen saturation (SO2) decreased after smoke
      inhalation at different time points (P<0.01); while, partial blood carbon dioxide
      (PaCO2), wet-to-dry weight ratio, leukocytes count, protein concentration and
      inflammatory cytokines in BALF increased after smoke exposure (P<0.01). More
      importantly, both immunohistochemical staining and Western blot results showed
      that ACE and ACE2 expression in lungs from the experimental groups significantly
      increased compared with that of the control group (P<0.05). This study indicated
      that inflammation pulmonary edema and histological changes resulted from smoke
      inhalation induced lung injury were possibly attributed to abnormal expression of
      ACE and ACE2 related pathway.

PMID- 25981294
TI  - A high performance P(VDF-TrFE) nanogenerator with self-connected and vertically
      integrated fibers by patterned EHD pulling.
AB  - Piezoelectricity based energy harvesting from mechanical vibrations has attracted
      extensive attention for its potential application in powering wireless mobile
      electronics recently. Here, a patterned electrohydrodynamic (EHD) pulling
      technology was proposed to fabricate a new self-connected, piezoelectric fiber
      array vertically integrated P(VDF-TrFE) nanogenerator, with a molecular poling
      orientation fully aligned to the principal excitation for maximized conversion
      and a well-bridged electrode pair for efficient charge collection. The
      nanogenerator is fabricated in a novel way by applying a voltage across an
      electrode pair sandwiching an air gap and an array of shallow micropillars,
      during which the EHD force tends to pull the micropillars upward, generating a
      microfiber array finally in robust contact with the upper electrode. Such a
      thermoplastic and EHD deformation of the microfibers, featured simultaneously by
      an electric field and by a microfiber elongation dominantly vertical to the
      electrode, leads to a poling orientation of P(VDF-TrFE) well coincident with the
      principal strain for the generator excited by a force normal to the electrodes.
      The as-prepared piezoelectric device exhibits an enhanced output voltage up to
      4.0 V and a current of 2.6 MUA, therefore the piezoelectric voltage was enhanced
      to 5.4 times that from the bulk film. Under periodic mechanical impact, electric
      signals are repeatedly generated from the device and used to power a seven
      segment indicator, RBGY colored light-emitting diodes, and a large-scale liquid
      crystal display screen. These results not only provide a tool for fabricating 3D
      piezoelectric polymers but offer a new type of self-connected nanogenerator for
      the next generation of self-powered electronics. 

PMID- 25981296
TI  - Role of post-translational modifications on structure, function and pharmacology
      of class C G protein-coupled receptors.
AB  - G protein-coupled receptors are divided into three classes (A, B and C) based on
      homology of their seven transmembrane domains. Class C is the smallest class with
      22 human receptor subtypes including eight metabotropic glutamate (mGlu1-8)
      receptors, two GABAB receptors (GABAB1 and GABAB2), three taste receptors (T1R1
      3), one calcium-sensing (CaS) receptor, one GPCR, class C, group 6, subtype A
      (GPRC6) receptor, and seven orphan receptors. G protein-coupled receptors undergo
      a number of post-translational modifications, which regulate their structure,
      function and/or pharmacology. Here, we review the existence of post-translational
      modifications in class C G protein-coupled receptors and their regulatory roles,
      with particular focus on glycosylation, phosphorylation, ubiquitination,
      SUMOylation, disulphide bonding and lipidation. 

PMID- 25981295
TI  - Role and therapeutic potential of G-protein coupled receptors in breast cancer
      progression and metastases.
AB  - G-protein-coupled receptors (GPCRs) comprise a large family of cell-surface
      receptors, which have recently emerged as key players in tumorigenesis,
      angiogenesis and metastasis. In this review, we discussed our current
      understanding of the many roles played by GPCRs in general, and particularly
      Angiotensin II type I receptor (AGTR1), a member of the seven-transmembrane
      spanning G-protein coupled receptor superfamily, and its significance in breast
      cancer progression and metastasis. We have also discussed different strategies
      for targeting AGTR1, and its ligand Angiotension II (Ang II), which might unravel
      unique opportunities for breast cancer prevention and treatment. For example,
      AGTR1 blockers (ARBs) which are already in clinical use for treating
      hypertension, merit further investigation as a therapeutic strategy for AGTR1
      positive cancer patients and may have the potential to prevent Ang II-AGTR1
      signalling mediated cancer pathogenesis and metastases. 

PMID- 25981297
TI  - Protective effects of tirofiban on ischemia/reperfusion-induced renal injury in
      vivo and in vitro.
AB  - Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is widely used in the
      management of patients with unstable angina or myocardial infarction, and shows
      protective effects on ischemia/reperfusion (I/R) injured heart. Whether or not it
      has protective effect on I/R injured kidney is not known. The present in vivo and
      in vitro study found that serum creatinine (SCR) and blood urea nitrogen (BUN)
      were significantly increased in I/R rats, accompanied by histopathological damage
      of the kidney. Apoptotic cells, leukocyte infiltration and ROS production were
      increased in I/R rats. Pretreatment by intravenous injection of tirofiban
      (200MUg/kg) reduced SCR and BUN levels, ameliorated renal histopathological
      changes, and decreased ROS production, cell apoptosis and leukocyte infiltration
      in I/R injured kidney. Our further study showed that the protection of tirofiban
      might be associated with the restoration of eNOS/iNOS balance, since inhibition
      of NO production blocked the tirofiban-mediated renal protection on I/R injury.
      The present in vivo and in vitro study indicated that tirofiban pretreatment
      exerts a protective effect on I/R injury in kidney through regulation of
      eNOS/iNOS balance. 

PMID- 25981298
TI  - GPCR signaling and cardiac function.
AB  - G protein-coupled receptors (GPCRs), such as beta-adrenergic and angiotensin II
      receptors, located in the membranes of all three major cardiac cell types, i.e.
      myocytes, fibroblasts and endothelial cells, play crucial roles in regulating
      cardiac function and morphology. Their importance in cardiac physiology and
      disease is reflected by the fact that, collectively, they represent the direct
      targets of over a third of the currently approved cardiovascular drugs used in
      clinical practice. Over the past few decades, advances in elucidation of their
      structure, function and the signaling pathways they elicit, specifically in the
      heart, have led to identification of an increasing number of new molecular
      targets for heart disease therapy. Here, we review these signaling modalities
      employed by GPCRs known to be expressed in the cardiac myocyte membranes and to
      directly modulate cardiac contractility. We also highlight drugs and drug classes
      that directly target these GPCRs to modulate cardiac function, as well as
      molecules involved in cardiac GPCR signaling that have the potential of becoming
      novel drug targets for modulation of cardiac function in the future. 

PMID- 25981299
TI  - Targeting chemokine receptors in disease--a case study of CCR4.
AB  - Since their early 1990s, the chemokine receptor family of G protein-coupled
      receptors (GPCRs) has been the source of much pharmacological endeavour. Best
      known for their key roles in recruiting leukocytes to sites of infection and
      inflammation, the receptors present themselves as plausible drug targets for
      therapeutic intervention. In this article, we will focus our attention upon CC
      Chemokine Receptor Four (CCR4) which has been implicated in diseases as diverse
      as allergic asthma and lymphoma. We will review the discovery of the receptors
      and their ligands, their perceived roles in disease and the successful targeting
      of CCR4 by both small molecule antagonists and monoclonal antibodies. We will
      also discuss future directions and strategies for drug discovery in this field. 

PMID- 25981300
TI  - Structural mechanism of G protein activation by G protein-coupled receptor.
AB  - G protein-coupled receptors (GPCRs) are a family of membrane receptors that
      regulate physiology and pathology of various organs. Consequently, about 40% of
      drugs in the market targets GPCRs. Heterotrimeric G proteins are composed of
      alpha, beta, and gamma subunits, and act as the key downstream signaling
      molecules of GPCRs. The structural mechanism of G protein activation by GPCRs has
      been of a great interest, and a number of biochemical and biophysical studies
      have been performed since the late 80's. These studies investigated the interface
      between GPCR and G proteins and the structural mechanism of GPCR-induced G
      protein activation. Recently, arrestins are also reported to be important
      molecular switches in GPCR-mediated signal transduction, and the physiological
      output of arrestin-mediated signal transduction is different from that of G
      protein-mediated signal transduction. Understanding the structural mechanism of
      the activation of G proteins and arrestins would provide fundamental information
      for the downstream signaling-selective GPCR-targeting drug development. This
      review will discuss the structural mechanism of GPCR-induced G protein activation
      by comparing previous biochemical and biophysical studies. 

PMID- 25981302
TI  - Pharmacological interaction between LABAs and LAMAs in the airways: optimizing
      synergy.
AB  - Nowadays there is solid clinical information for combining beta2-agonists and
      anti-muscarinic agents, although the nature (additive or synergistic) of the net
      clinical result obtained by co-administration of these two classes of
      bronchodilators is not completely elucidated from a pharmacological point of
      view. Recent preclinical studies demonstrated that combining a long-acting beta2
      agonist (LABA) with a long-acting anti-muscarinic agent (LAMA) provides
      synergistic benefit on airway smooth muscle relaxation, which may have major
      implications for the use of LABA/LAMA combinations in the treatment COPD. Indeed,
      the LABA/LAMA synergism has been proved also in patients with moderate-to-severe
      COPD. Nevertheless, there is still a strong medical need for dose-finding
      clinical trials designed to identify the most favourable doses of LABA/LAMA
      combinations able to induce a real synergism. We strongly believe that the Bliss
      Independence theory represents an effective model for investigating the cross
      talk between beta2-adrenoreceptor and the muscarinic pathways leading to the
      synergistic interaction between beta2-agonists and anti-muscarinic agents. In any
      case, the possibility of eliciting a synergistic bronchodilator effect when
      combining a LABA and a LAMA suggests that the therapeutic approach proposed by
      GOLD recommendations to only use LABA/LAMA combination in more severe COPD
      patients who are not controlled by a single bronchodilator should be
      reconsidered. We support the possibility of an early intervention with low doses
      of LABA/LAMA combination to optimize bronchodilation and reduce the risk of
      adverse events that characterize both LABAs and LAMAs, especially when
      administered at the full doses currently approved for the treatment of COPD. 

PMID- 25981301
TI  - Opioid receptors: Structural and mechanistic insights into pharmacology and
      signaling.
AB  - Opioid receptors are important drug targets for pain management, addiction, and
      mood disorders. Although substantial research on these important subtypes of G
      protein-coupled receptors has been conducted over the past two decades to
      discover ligands with higher specificity and diminished side effects, currently
      used opioid therapeutics remain suboptimal. Luckily, recent advances in
      structural biology of opioid receptors provide unprecedented insights into opioid
      receptor pharmacology and signaling. We review here a few recent studies that
      have used the crystal structures of opioid receptors as a basis for revealing
      mechanistic details of signal transduction mediated by these receptors, and for
      the purpose of drug discovery. 

PMID- 25981303
TI  - Structural insights into ligand recognition and selectivity for classes A, B, and
      C GPCRs.
AB  - The G protein-coupled receptor (GPCR) superfamily constitutes the largest
      collection of cell surface signaling proteins with approximately 800 members in
      the human genome. GPCRs regulate virtually all aspects of physiology and they are
      an important class of drug targets with ~30% of drugs on the market targeting a
      GPCR. Breakthroughs in GPCR structural biology in recent years have significantly
      expanded our understanding of GPCR structure and function and ushered in a new
      era of structure-based drug design for GPCRs. Crystal structures for nearly
      thirty distinct GPCRs are now available including receptors from each of the
      major classes, A, B, C, and F. These structures provide a foundation for
      understanding the molecular basis of GPCR pharmacology. Here, we review
      structural mechanisms of ligand recognition and selectivity of GPCRs with a focus
      on selected examples from classes A, B, and C, and we highlight major unresolved
      questions for future structural studies. 

PMID- 25981305
TI  - Effects of palmitoylethanolamide and silymarin combination treatment in an animal
      model of kidney ischemia and reperfusion.
AB  - The aim of this study was to investigate the efficacy of PEA+silymarin as a
      combination treatment in a mouse model of renal I/R and to verify whether
      PEA+silymarin could exert more potent effects compared to the single substances
      even if administered at lower doses. Mice were subjected to bilateral renal
      artery occlusion (30min) and reperfusion (6h) and received intraperitoneally
      silymarin (100, 30 and 10mg/kg) or PEA (1mg/kg) or PEA (1mg/kg)+silymarin
      (10mg/kg) 15min before release of clamps. Specific indicators of renal
      dysfunction, tubular injury, myeloperoxidase activity and malondialdehyde levels
      were measured. The nuclear factor kappaB pathway and apoptotic mechanisms were
      also investigated. The treatment with silymarin reduced kidney dysfunction,
      histological damage, neutrophil infiltration and oxidative stress in a dose
      dependent manner. Furthermore, PEA+silymarin showed a significant potentiated
      effect. Therefore, NF-kappaB and apoptosis pathways were also significantly
      inhibited. Our results clearly demonstrate that PEA+silymarin treatment
      attenuated the degree of renal inflammation. 

PMID- 25981306
TI  - Comparative morphology of the snake spectacle using light and transmission
      electron microscopy.
AB  - OBJECTIVE: To determine the interspecific variation in the morphology of the
      snake spectacle. ANIMALS STUDIED: About 43 snakes of 14 different species,
      belonging to three different families: Boidae, Colubridae, and Pythonidae.
      PROCEDURE: The spectacles were examined by light and transmission electron
      microscopy. The thickness of the stromal layer was measured and the location of
      the blood vessels was noted. The shape of the transition zone located at the rim
      of the spectacle and the presence of pigment herein were also recorded. RESULTS:
      The spectacles of all species examined consisted of three layers. The outer
      epithelium was made of basal cells with overlaying keratin layers, the stroma
      comprised layers of organized collagen fibrils, and the inner epithelium was a
      layer of squamous cells with microvilli. Blood vessels were found in the stroma
      of all spectacles: in boas and pythons in the middle layers of the stroma and in
      colubrids adjacent to the inner epithelium. Boas and pythons were endowed with
      the thickest stromal layers (81-132 MUm) compared to colubrids (9-95 MUm). Boas
      and pythons had a convex transition zone, while the transition zone of the
      colubrids exhibited a steady increase in spectacle thickness toward the hinge
      region. The transition zone contained pigment in boas and pythons. CONCLUSION:
      The overall morphology of the spectacle was similar among the major families of
      snakes. However, the location of blood vessels and appearance of transition zone
      differed, as did the overall thickness of the spectacle.

PMID- 25981307
TI  - Perivascular epithelioid cell neoplasm (PEComa) of the uterus: A systematic
      review.
AB  - BACKGROUND: Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal
      tumor. Gynecological PEComas account for just over one-fourth of the overall
      PEComa cases reported in the literature. Surgery is the most recommended primary
      treatment while adjuvant therapy is generally reserved for high-risk cases.
      However, the best management of this neoplasia has not been well established,
      primarily because of the paucity of cases described to date. OBJECTIVES: The aim
      of this systematic review is to summarize what is known thus far regarding the
      etiopathogenesis, clinical and pathologic features of PEComas, focusing also on
      the most valid treatment options for uterine cases. DATA SOURCES: Pubmed articles
      on PEComas published in various journals over the past 70 years were analyzed.
      CONCLUSIONS AND KEY FINDINGS: Although the optimal treatment of gynecological
      PEComas is controversial, surgical resection remains the cornerstone. The use of
      adjuvant treatment is warranted in high risk patients to increase disease
      control. A multidisciplinary approach should be key in treatment decision-making
      regarding gynecological PEComas.

PMID- 25981304
TI  - Galpha(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years
      later.
AB  - Heterologous sensitization of adenylyl cyclase (also referred to as
      superactivation, sensitization, or supersensitization of adenylyl cyclase) is a
      cellular adaptive response first described 40 years ago in the laboratory of Dr.
      Marshall Nirenberg. This apparently paradoxical cellular response occurs
      following persistent activation of Galphai/o-coupled receptors and causes marked
      enhancement in the activity of adenylyl cyclases, thereby increasing cAMP
      production. Since our last review in 2005, significant progress in the field has
      led to a better understanding of the relevance of, and the cellular biochemical
      processes that occur during the development and expression of heterologous
      sensitization. In this review we will discuss the recent advancements in the
      field and the mechanistic hypotheses on heterologous sensitization. 

PMID- 25981308
TI  - Application of wireless electrical non-fiberoptic endoscope: Potential benefit
      and limitation in endoscopic surgery.
AB  - INTRODUCTION: Conventional rigid endoscope requires a bundle of optic fibers for
      illumination and a set of camera for viewing body cavity. The design is bulky in
      the hand-held part and the laterally positioned optic fibers may hinder
      manipulation of instruments, especially in single port surgery. We designed a
      simplified unit to replace conventional endoscope. MATERIALS AND METHODS: We used
      an independent front image sensor along with six light emitting diode crystals. A
      wireless module working in 2.4 GHz and its antenna were integrated into the hand
      help part. Two 800 mA batteries were used for power supply. The study was tested
      in two 35 kg pigs. Some simple thoracoscopic and laparoscopic operations were
      simulated to test the reliability and surgeon's acceptability. RESULTS: Signal
      Noise ratio can be controlled well in the setting of the operative room. Signal
      transmission was influenced significantly when covered by damped gauze or drape.
      The best quality of wireless transmission is through line-of-sight. Dropping
      frame is less than 1 frame per second in 99% time period during the test.
      CONCLUSION: Wireless modules in the design of rigid endoscope may be a plausible
      option with good acceptability.

PMID- 25981310
TI  - Opioid abuse and depression in adolescents: Results from the National Survey on
      Drug Use and Health.
AB  - OBJECTIVE: To investigate the association of major depressive episode (MDE) with
      nonmedical prescription opioid use (NMPOU) and opioid abuse/dependence among
      adolescents aged 12 to 17. METHODS: We analyzed 5 years of data from the National
      Survey on Drug Use and Health (NSDUH). We used logistic regressions to study the
      relationship between MDE and NMPOU among all adolescents, as well as the
      relationship of MDE with opioid abuse/dependence among adolescents with NMPOU.
      Other covariates included: sociodemographics, alcohol abuse/dependence, nonopioid
      drug abuse/dependence, delinquency, school performance, religious services
      attendance, and family support/supervision. RESULTS: In the sample of all
      adolescents, 6% reported past year NMPOU, and 8% reported past year MDE. When
      NMPOU and MDE were comorbid, MDE usually preceded the NMPOU. In the sample of
      adolescents with NMPOU, 15% reported past year opioid abuse/dependence, and 20%
      reported past year MDE. In adjusted logistic regression, MDE was associated with
      both NMPOU (OR=1.51, p<0.001) among all adolescents and opioid abuse/dependence
      (OR=2.18, p<0.001) among adolescents with NMPOU. CONCLUSION: MDE occurs commonly
      in adolescents and is associated with NMPOU and opioid abuse/dependence. In terms
      of population attributable risk, which is a function of both the prevalence and
      the strength of the association, MDE is an important risk factor for NMPOU among
      adolescents and opioid abuse/dependence among adolescents with NMPOU. Preventive
      and clinical programs to decrease NMPOU and opioid abuse/dependence among
      adolescents should consider the prominent role of depression.

PMID- 25981309
TI  - Potential clinical impact of advanced imaging and computer-aided diagnosis in
      chest radiology: importance of radiologist's role and successful observer study.
AB  - This review paper is based on our research experience in the past 30 years. The
      importance of radiologists' role is discussed in the development or evaluation of
      new medical images and of computer-aided detection (CAD) schemes in chest
      radiology. The four main topics include (1) introducing what diseases can be
      included in a research database for different imaging techniques or CAD systems
      and what imaging database can be built by radiologists, (2) understanding how
      radiologists' subjective judgment can be combined with technical objective
      features to improve CAD performance, (3) sharing our experience in the design of
      successful observer performance studies, and (4) finally, discussing whether the
      new images and CAD systems can improve radiologists' diagnostic ability in chest
      radiology. In conclusion, advanced imaging techniques and
      detection/classification of CAD systems have a potential clinical impact on
      improvement of radiologists' diagnostic ability, for both the detection and the
      differential diagnosis of various lung diseases, in chest radiology. 

PMID- 25981311
TI  - The interest in eight new psychoactive substances before and after scheduling.
AB  - BACKGROUND: In recent years the recreational use of new psychoactive substances
      (NPS) has increased. NPS are considered a threat to public health and the main
      response to this threat is to make the selling and buying of these substances
      illegal. In Sweden, during the last 5 years, 62 new substances have been
      classified as narcotics but little is known of the effects of making a particular
      substance illegal. The aim of this work is to study how legal status influences
      the interest in NPS in Sweden. METHODS: Forty-five thousand posts made in a
      Swedish Internet discussion forum (Flashback Forum) related to eight NPS (MDPV,
      Methylone, 4-MEC, 4-HO-MET, MXE, 6-APB, AH-7921, and 3-MMC) were used to derive
      time-dependent measures of interest in these substances. Intervention analyses
      were used to investigate the effects of legal status on the forum interest.
      RESULTS: For all eight substances the activity on the forum (measured as number
      of posts per day) showed a drastic decrease around the time of classification.
      The statistical analysis showed that in seven of eight cases, the drop in
      activity could be accounted for by the legal status of the substances.
      CONCLUSIONS: The legal status of the substances was shown to have a substantial
      effect on the interest in the substances. The novel measure used to trace the
      interest in particular NPS could be a useful tool to follow trends in substance
      use in almost real-time.

PMID- 25981313
TI  - Successful radiofrequency ablation of atrial flutter causing hemodynamic
      instability in a patient with recent myocardial infarction.
AB  - Atrial flutter (AFL) is a common arrhythmia which may decrease cardiac output and
      may cause embolic events. Direct current (DC) cardioversion, medical
      cardioversion and radiofrequency (RF) ablation are therapeutic options, but over
      all RF ablation therapy has the longest event free period. Although development
      of AFL after myocardial infarction is quite common it may spontaneously recover
      or results in atrial fibrillation. Herein we report a patient with medical and
      electrical cardioversion resistant AFL which developed in the early post
      myocardial infarction period causing hemodynamic instability, who was
      successfully treated with RF catheter ablation. 

PMID- 25981312
TI  - The effects of unemployment and perceived job insecurity: a comparison of their
      association with psychological and somatic complaints, self-rated health and life
      satisfaction.
AB  - PURPOSE: Research has provided convincing evidence for the adverse effects of
      both short- and long-term unemployment, and perceived job insecurity on
      individuals' health and well-being. This study aims to go one critical step
      further by comparing the association between short- and long-term unemployment,
      and perceived job insecurity with a diverse set of health and well-being
      indicators. METHODS: We compare four groups: (1) secure permanent employees (N =
      2257), (2) insecure permanent employees (N = 713), (3) short-term unemployed (N =
      662), and (4) long-term unemployed (N = 345) using cross-sectional data from the
      nationally representative Living Conditions Survey in Finland. RESULTS:
      Covariance analyses adjusted for background variables support findings from
      earlier studies that long-term unemployment and perceived job insecurity are
      detrimental: short-term unemployed and secure permanent employees experienced
      fewer psychological complaints and lower subjective complaints load, reported a
      higher self-rated health, and were more satisfied with their life compared to
      long-term unemployed and insecure permanent employees. Second, whereas
      unemployment was found to be more detrimental than insecure employment in terms
      of life satisfaction, insecure employment was found to be more detrimental than
      unemployment in terms of psychological complaints. No differences were found
      regarding subjective complaints load and self-rated health. CONCLUSIONS: Our
      findings suggest that (1) insecure employment relates to more psychological
      complaints than short-term unemployment and secure permanent employment, (2)
      insecure employment and long-term unemployment relate to more subjective
      complaints load and poorer health when compared to secure permanent employment,
      and (3) insecure employment relates to higher life satisfaction than both short-
      and long-term unemployment.

PMID- 25981314
TI  - Minimally-invasive LVAD Implantation: State of the Art.
AB  - Nowadays, the worldwide number of left ventricular assist devices (LVADs) being
      implanted per year is higher than the number of cardiac transplantations. The
      rapid developments in the field of mechanical support are characterized by
      continuous miniaturization and enhanced performance of the pumps, providing
      increased device durability and a prolonged survival of the patients. The
      miniaturization process enabled minimally-invasive implantation methods, which
      are associated with generally benefitting the overall outcome of patients.
      Therefore, these new implantation strategies are considered the novel state of
      the art in LVAD surgery. In this paper we provide a comprehensive review on the
      existing literature on minimally-invasive techniques with an emphasis on the
      different implantation approaches and their individual surgical challenges. 

PMID- 25981315
TI  - Pharmacological and non pharmacological strategies in the management of coronary
      artery disease and chronic kidney disease.
AB  - Patients with advanced chronic kidney disease (CKD), including those treated with
      dialysis, are at high risk for the development of cardiovascular disease (CVD).
      CVD accounts for 45-50% of deaths among dialysis patients. Therapy of acute and
      chronic coronary heart disease (CHD) that is effective in the general population
      is frequently less effective in patients with advanced CKD. Drug therapy in such
      patients may require dose modification in some cases. Oral anti-platelet drugs
      are less effective in those with advanced CKD than in persons with normal or near
      normal renal function. The intravenous antiplatelet drugs eptifibatide and
      tirofiban both require dose reductions in patients with advanced CKD. Enoxaparin
      requires dose reduction in early stage CKD and is contraindicated in hemodialysis
      patients. Unfractionated heparin and warfarin maybe used without dose adjustment
      in CKD patients. Atenolol, acetbutolol and nadolol may require dose adjustments
      in CKD. Metoprolol and carvedilol do not. Calcium channel blockers and nitrates
      do not require dose adjustment, whereas ranolazine does. Angiotensin converting
      enzyme inhibitors and angiotensin receptor blockers may safely be used in CKD
      patients with close observation for hyperkalemia. The safety of spironolactone in
      such patients is questionable. Statins are less effective in reducing
      cardiovascular complication in CKD patients and their initiation is not
      recommended in dialysis patients. Coronary artery bypass grafting is associated
      with higher shortterm mortality, but better long-term morbidity and mortality
      than percutaneous coronary interventions in patients with advanced CKD with non
      ST segment ACS and chronic CHD. 

PMID- 25981316
TI  - Chicago's Sanitary and Ship Canal sediment: Polycyclic aromatic hydrocarbons,
      polychlorinated biphenyls, brominated flame retardants, and organophosphate
      esters.
AB  - The Chicago Sanitary and Ship Canal (CSSC) links the Great Lakes to the
      Mississippi River starting in downtown Chicago. In addition to storm water, the
      CSSC receives water from Chicago's wastewater treatment plants (WWTP). Such
      effluents are known to be sources of organic pollutants to water and sediment.
      Therefore in 2013, we collected 10 sediment samples from the CSSC and measured
      the concentrations of polycyclic aromatic hydrocarbons (PAHs), polychlorinated
      biphenyls (PCBs), brominated flame retardants, and organophosphate esters (OPEs).
      Geometric mean concentrations of the summed concentrations of 16 PAHs ranged from
      11,000 to 420,000 ng/g dw, with the highest concentrations located at each end of
      the canal. Total PCB concentrations had a geometric mean of 1,400 +/- 500 ng/g
      dw. Brominated flame retardants were separated into two groups: polybrominated
      diphenyl ethers (PBDEs) and non-PBDEs. Concentrations of PBDEs and those of the
      non-PBDE flame retardants had a geometric average of 83 +/- 19 and 7.0 +/- 5.8
      ng/g dw, respectively. The summed concentrations of 8 OPEs ranged from 470 to
      2,800 ng/g dw, with the highest concentration detected at a site located
      downstream of the Stickney water reclamation plant. Using ANOVA results, some
      hypotheses on sources to the CSSC could be formulated: downtown Chicago is
      probably a source of PAHs, the Cal-Sag Channel may be a source of PCBs, and
      neither the WWTP nor the Cal-Sag Channel seem to be significant sources of
      brominated flame retardants or OPEs.

PMID- 25981317
TI  - Estimation of the total concentration of perfluoroalkyl acids (PFAA) in human
      serum: Data from NHANES 2005-2012.
AB  - While selected perfluoroalkyl acids/substances (PFAAs) like perfluorooctanoate
      (PFOA) and perfluorooctane sulfonate (PFOS) have been detected and measured in
      laboratory, a method to estimate the total concentration of PFAAs (?PFAA) in
      serum has not been developed. Because of the health concerns associated with
      PFAAs and because of the inability of every laboratory to measure every PFAA as
      well as because of the non-availability of sensitive enough equipment to be able
      to detect very small amounts of certain PFAAs, it is of interest to know ?PFAA.
      We used data from the National Health and Nutrition Examination Survey for the
      years 2005-2012 to develop regression models to estimate ?PFAA by using the
      levels of PFOA and PFOS only. While data for 2005-2008 were used to develop
      regression models, data for 2009-2012 were used to evaluate the accuracy of the
      developed models. Over 63% of observed values for evaluation data were found to
      be within 10% of the predicted values. The model so developed can be used with
      just the knowledge of the age, gender, and concentrations of PFOA and PFOS. While
      the data used to develop the model were generated in U.S., the model can be used
      to estimate ?PFAA for data collected in North America and Europe and probably
      elsewhere in the world. 

PMID- 25981318
TI  - Forcing contact inhibition of locomotion.
AB  - Contact inhibition of locomotion drives a variety of biological phenomenon, from
      cell dispersion to collective cell migration and cancer invasion. New imaging
      techniques have allowed contact inhibition of locomotion to be visualised in vivo
      for the first time, helping to elucidate some of the molecules and forces
      involved in this phenomenon. 

PMID- 25981319
TI  - Author's Response: Cognitive devices and dictionaries: substance, format and
      funding.

PMID- 25981320
TI  - Make the Dictionary of Epidemiology open access.

PMID- 25981321
TI  - No evidence that genetically reduced 25-hydroxyvitamin D is associated with
      increased risk of ischaemic heart disease or myocardial infarction: a Mendelian
      randomization study.
AB  - BACKGROUND: Low plasma 25-hydroxyvitamin D [p-25(OH)D] is associated with
      increased risk of ischaemic heart disease and with the subgroup myocardial
      infarction. However, whether this association is causal or due to confounding or
      reverse causation is presently unknown. We tested the hypothesis that genetically
      reduced plasma 25(OH)D is associated with increased risk of ischaemic heart
      disease and myocardial infarction. METHODS: We used a Mendelian randomization
      design in the Copenhagen City Heart Study, the Copenhagen General Population
      Study, and the Copenhagen Ischaemic Heart Disease Study. Two 25(OH)D reducing
      genetic variants in the DCHR7 gene (rs7944926 and rs11234027) and two in the
      CYP2R1 gene (rs10741657 and rs12794714) were genotyped in 92 416 participants of
      Danish descent, of whom 14 455 developed ischaemic heart disease (ICD-8:410-414;
      ICD-10:I20-I25) and 7061 myocardial infarction (ICD-8:410: ICD-10:I21-I22) from
      1977 through 2011. P-25(OH)D was measured in 36,089 participants. APOE genotype
      was included as a positive control for risk of ischaemic heart disease. RESULTS:
      The multivariable adjusted hazard ratios for lowest vs highest quartile of
      25(OH)D were 1.82 [95% confidence interval (CI): 1.42-2.32] for ischaemic heart
      disease. Each allele increase in a combined allele score was associated with a
      1.9-nmol/l decrease in p-25(OH)D (P = 7 * 10(-55); R(2) = 0.9%). The genetic
      variants were, however, not associated with increased risk of ischaemic heart
      disease. In instrumental variable analysis, the odds ratio for ischaemic heart
      disease for a genetically 25-nmol/l decrease in p-25(OH)D was 0.98 (95% CI: 0.76
      1.26), with a corresponding observational hazard ratio by Cox regression of 1.07
      (1.01-1.13). Similarly, with myocardial infarction as the outcome, observational
      analyses suggested an increased risk with lower 25(OH)D, whereas genetic analyses
      suggested no causal effect. For APOE genotype, the odds ratio for ischaemic heart
      disease for a 1-mmol/l genetic increase in plasma total cholesterol
      concentrations was 1.23 (1.08-1.41), with a corresponding observational hazard
      ratio of 1.08 (1.04-1.14). CONCLUSION: We found no evidence to suggest that
      genetically reduced p-25(OH)D is associated with increased risk of ischaemic
      heart disease or myocardial infarction.

PMID- 25981322
TI  - [Endocrine sequelae after treatment of pediatric cancer: From childhood to
      adulthood].
AB  - Endocrine sequelae are among the most frequently reported complications in
      childhood cancer survivors, affecting 40 to 60% of these patients during adult
      life. Most of these complications are the result of cranial radiation therapy for
      brain or facial tumor, lymphoma or leukemia. The present review describes the
      main endocrine disturbances observed in this population, including disorders of
      hypothalamic-pituitary axis, especially the frequently observed growth hormone
      deficiency and disorders of puberty, thyroid and parathyroid dysfunction, obesity
      and metabolic syndrome, alterations in glucose metabolism and decreased bone
      mineral density. Gonadal dysfunction is not described, since it is detailed in
      another chapter. During childhood, prompt diagnosis and management of endocrine
      complications allow improvement of final height outcome and body composition
      (lean body mass and bone mass), reducing morbidity and impaired quality of life
      later in adulthood. Risk of developing a second neoplasm after growth hormone
      therapy in cancer survivors is also addressed. Life-long follow-up and management
      of endocrine deficiencies are essential to reduce late morbidity especially
      cardiovascular risk, and to diagnose late-onset deficiencies as well as radiation
      induced thyroid nodules and cancer.

PMID- 25981323
TI  - Relationship of betatrophin with youth onset type 2 diabetes among Asian Indians.
AB  - BACKGROUND AND AIMS: Betatrophin is emerging as a marker for compensatory beta
      cell proliferation. While betatrophin has been mainly investigated in adults,
      there is a lack of data on betatrophin levels in youth-onset type 2 diabetes
      mellitus (T2DM-Y). The aim of this study was to determine levels of betatrophin
      and its association with T2DM-Y in Asian Indian participants. METHODS: We
      recruited 100 individuals with normal glucose tolerance (NGT; n=50) and newly
      diagnosed cases (within 18 months of first diagnosis) of T2DM-Y (n=50) with onset
      between 12 and 24 years of age from a large tertiary diabetes center in Chennai
      in southern India. Insulin resistance was measured by homeostatic model (HOMA-IR)
      and insulin secretion by oral disposition index (DIO). Betatrophin levels were
      measured by enzyme-linked immunosorbent assay. RESULTS: Betatrophin levels were
      significantly lower in the T2DM-Y group compared with the NGT group (803 vs 1104
      pg/ml, p<0.001). Betatrophin showed a significant inverse correlation with waist
      circumference (p=0.035), HOMA-IR (p<0.001), fasting and 2 h postprandial glucose
      (p<0.01), glycated hemoglobin (p=0.019) and a positive correlation with fasting C
      peptide (p<0.001) and DIO (p=0.012). In regression analysis, betatrophin was
      independently associated with T2DM-Y even after adjustment for age, gender, and
      waist circumference (OR per standard deviation: 0.562, 95% CI: 0.342-0.899,
      p=0.019). However, the association was lost when HOMA-IR was included in the
      model (OR: 1.141, 95% CI: 0.574-2.249; p=0.646). CONCLUSION: Betatrophin levels
      are lower in T2DM-Y and this association is likely mediated through insulin
      resistance.

PMID- 25981324
TI  - Polymorphisms of rs174616 in the FADS1-FADS2 gene cluster is associated with a
      reduced risk of type 2 diabetes mellitus in northern Han Chinese people.
AB  - AIMS: Several studies have shown associations between the composition of
      polyunsaturated fatty acids (PUFAs) in various tissues and type 2 diabetes
      mellitus (T2DM) development in European populations. Genetic variants of fatty
      acid desaturase (FADS) contribute to the variations of PUFA composition. Here we
      have explored whether similar correlations are also true among Chinese Han
      people. METHODS: A case-control study was employed to examine this correlation in
      Han Chinese people. The study included 421 healthy adults and 331 T2DM patients.
      RESULTS: The ratio of arachidonic acid/linoleic acid (AA/LA), which reflects
      Delta6 desaturase activity, was significantly increased in T2DM patients.
      Furthermore, the ratio of eicosapentaenoic acid/alpha-linolenic acid (EPA/ALA),
      which reflects Delta5 desaturase activity, was markedly decreased in T2DM
      patients. Importantly, among four single nucleotide polymorphisms (rs174545,
      rs2072114, rs174602 and rs174616) in the FADS1-FADS2 gene cluster, only minor
      allele (T) of rs174616 was associated with decreased risk of T2DM in both
      codominant and dominant models after adjustment for age, gender and BMI.
      Furthermore, the ratio of AA/LA in both controls and T2DM was reduced in T
      carriers while an increased proportion of LA was seen in T2DM patients compared
      with control patients. CONCLUSION: These data suggest that in northern Han
      Chinese people, the minor allele (T) of rs174616 in the FADS1-FADS2 gene cluster
      is associated with a decreased conversion rate of LA to AA, which may contribute
      to decreased reduced risk of developing T2DM.

PMID- 25981326
TI  - Structural Allografts and Porous Metal Cones - Major Findings Remain Unchanged.
      In reply.

PMID- 25981325
TI  - Bile acid binding resin improves hepatic insulin sensitivity by reducing
      cholesterol but not triglyceride levels in the liver.
AB  - AIMS: Bile acid binding resin (BAR) improves glycaemic control in patients with
      type 2 diabetes. Although the mechanism is hypothesised to involve the clearance
      of excess hepatic triglyceride, this hypothesis has not been examined in
      appropriately designed studies. Therefore, we investigated whether reduced
      hepatic triglyceride deposition is involved in BAR-mediated improvements in
      glycaemic control in spontaneous fatty liver diabetic mice without dietary
      interventions. METHODS: Male 6-week-old fatty liver Shionogi (FLS) mice were fed
      a standard diet without or with 1.5% BAR (colestilan) for 6 weeks. Glucose
      tolerance, insulin sensitivity, hepatic lipid content, and gene expression were
      assessed. A liver X receptor (LXR) agonist was also administered to activate the
      LXR pathway. We also retrospectively analysed the medical records of 21
      outpatients with type 2 diabetes who were treated with colestilan for >=6 months.
      RESULTS: BAR enhanced glucose tolerance and insulin sensitivity in FLS mice
      without altering fat mass. BAR improved hepatic insulin sensitivity, increased
      IRS2 expression, and decreased SREBP expression. BAR reduced hepatic cholesterol
      levels but not hepatic triglyceride levels. BAR also reduced the expression of
      LXR target genes, and LXR activation abolished the BAR-mediated improvements in
      glycaemic control. Colestilan significantly lowered serum cholesterol levels and
      improved glycaemic control in patients with type 2 diabetes. CONCLUSIONS: BAR
      improved hepatic insulin resistance in FLS mice by reducing hepatic cholesterol
      without affecting hepatic triglyceride levels or body fat distribution. Our study
      revealed that BAR improves glycaemic control at least in part by downregulating
      the hepatic cholesterol-LXR-IRS2 pathway.

PMID- 25981327
TI  - Long-Term Outcome of Acetabular Reconstruction Using a Kerboull-Type Acetabular
      Reinforcement Device with Hydroxyapetite Granule and Structural Autograft for
      AAOS type II and III Acetabular Defects.
AB  - We evaluated the clinical results of the reconstruction of acetabular bone
      deficiency using hydroxyapatite (HA) granules and structural autografts supported
      by a Kerboull-type acetabular reinforcement device at a minimum of 10 years
      follow-up. Between 1993 and 2003, 40 consecutive THA revisions were performed in
      37 patients with a mean age of 66.4 years. The mean follow-up period was 12.8
      years. Radiologically, 5 hips failed, of which 2 were revised. The survival rate
      of the acetabular component at 10 years was 100% in type II defects and 94.9% in
      the type III defects, using acetabular revision for loosening as the end point.
      Acetabular reconstruction with HA granules, structural autografts and a Kerboull
      type acetabular reinforcement device provided satisfactory clinical and
      radiological results at 12.8 years postoperatively. 

PMID- 25981328
TI  - Comparison of Acetabular Bone Resection, Offset, Leg Length and Post Operative
      Function Between Hip Resurfacing Arthroplasty and Total Hip Arthroplasty.
AB  - Controversy exists regarding the amount of acetabular bone resection,
      biomechanics and function of patients receiving either total hip arthroplasty
      (THA) or hip resurfacing arthroplasty (HRA). A cohort of patients undergoing 36
      mm ceramic-on-ceramic THA (89) or metal-on-metal HRA (86) were compared. No
      difference was observed when the ratio of native femoral head size was compared
      to the implanted acetabular component size (1.15 +/- 0.1 HRA c.f. 1.13 +/- 0.1
      THA). No difference was observed in acetabular offset, vertical centre of
      rotation or function (OHS mean 47 in both groups) but leg length discrepancy (1.8
      mm c.f. 5.5 mm) and femoral offset did differ (0.6 mm c.f. 4.1 mm). This
      demonstrates that 36 mm ceramic-on-ceramic THA is not associated with more bone
      resection than HRA and achieves equivalent function whilst avoiding the problems
      of metal-on-metal bearings.

PMID- 25981329
TI  - Internet-vs. group-delivered cognitive behavior therapy for insomnia: A
      randomized controlled non-inferiority trial.
AB  - The aim of this study was to compare guided Internet-delivered to group-delivered
      cognitive behavioral therapy (CBT) for insomnia. We conducted an 8-week
      randomized controlled non-inferiority trial with 6-months follow-up. Participants
      were forty-eight adults with insomnia, recruited via media. Interventions were
      guided Internet-delivered CBT (ICBT) and group-delivered CBT (GCBT) for insomnia.
      Primary outcome measure was the Insomnia Severity Index (ISI), secondary outcome
      measures were sleep diary data, depressive symptoms, response- and remission
      rates. Both treatment groups showed significant improvements and large effect
      sizes for ISI (Within Cohen's d: ICBT post = 1.8, 6-months follow-up = 2.1; GCBT
      post = 2.1, 6-months follow-up = 2.2). Confidence interval of the difference
      between groups post-treatment and at FU6 indicated non-inferiority of ICBT
      compared to GCBT. At post-treatment, two thirds of patients in both groups were
      considered responders (ISI-reduction > 7p). Using diagnostic criteria, 63% (ICBT)
      and 75% (GCBT) were in remission. Sleep diary data showed moderate to large
      effect sizes. We conclude that both guided Internet-CBT and group-CBT in this
      study were efficacious with regard to insomnia severity, sleep parameters and
      depressive symptoms. The results are in line with previous research, and
      strengthen the evidence for guided Internet-CBT for insomnia. TRIAL REGISTRATION:
      The study protocol was approved by, and registered with, the regional ethics
      review board in Linkoping, Sweden, registration number 2010/385-31.

PMID- 25981330
TI  - National Emergency Access Targets metrics of the emergency department-inpatient
      interface: measures of patient flow and mortality for emergency admissions to
      hospital.
AB  - BACKGROUND: Movement of emergency patients across the emergency department (ED)
      inpatient ward interface influences compliance with National Emergency Access
      Targets (NEAT). Uncertainty exists as to how best measure patient flow, NEAT
      compliance and patient mortality across this interface. OBJECTIVE: To compare the
      association of NEAT with new and traditional markers of patient flow across the
      ED-inpatient interface and to investigate new markers of mortality and NEAT
      compliance across this interface. METHODS: Retrospective study of consecutive
      emergency admissions to a tertiary hospital (January 2012 to June 2014) using
      routinely collected hospital data. The practical access number for emergency
      (PANE) and inpatient cubicles in emergency (ICE) are new measures reflecting
      boarding of inpatients in ED; traditional markers were hospital bed occupancy and
      ED attendance numbers. The Hospital Standardised Mortality Ratio (HSMR) for
      patients admitted via ED (eHSMR) was correlated with inpatientNEAT compliance
      rates. Linear regression analyses assessed for statistically significant
      associations (expressed as Pearson R coefficient) between all measures and
      inpatient NEAT compliance rates. RESULTS: PANE and ICE were inversely related to
      inpatient NEAT compliance rates (r = 0.698 and 0.734 respectively, P < 0.003 for
      both); no significant relation was seen with traditional patient flow markers.
      Inpatient NEAT compliance rates were inversely related to both eHSMR (r = 0.914,
      P = 0.0006) and all-patient HSMR (r = 0.943, P = 0.0001). CONCLUSIONS:
      Traditional markers of patient flow do not correlate with inpatient NEAT
      compliance in contrast to two new markers of inpatient boarding in ED (PANE and
      ICE). Standardised mortality rates for both emergency and all patients show a
      strong inverse relation with inpatient NEAT compliance.

PMID- 25981331
TI  - Degradation systems in heart failure.
AB  - Heart failure is a complex clinical syndrome that results from any structural or
      functional impairment of ventricular filling or the ejection of blood, and is a
      leading cause of morbidity and mortality in industrialized countries. The
      mechanisms underlying the development of heart failure are multiple, complex and
      not well understood. Cardiac mass and its homeostasis are maintained by the
      balance between protein synthesis and degradation, and an imbalance is likely to
      result in cellular dysfunction and disease. The protein degradation systems are
      the principle mechanisms for maintaining cellular homeostasis via protein quality
      control. Three major protein degradation systems have been identified, namely the
      calpain system, autophagy, and the ubiquitin proteasome system. Proinflammatory
      mediators involve the development and progression of heart failure. DNA and RNA
      degradation systems play a critical role in regulating inflammation and
      maintaining cellular homeostasis mediated by damaged DNA clearance and
      posttranscriptional regulation, respectively. This review discusses some recent
      advances in understanding the role of these degradation systems in heart failure.

PMID- 25981332
TI  - Living donor liver transplantation for Echinococcus Alveolaris: single-center
      experience.
AB  - Echinococcus alveolaris (EA) causes a hepatic zoonotic infection and behaves like
      a malignant tumor during invasion. Liver transplantation (LT) is the only
      curative treatment option for this unresectable disease. Here, we share our
      experience with living donor liver transplantation (LDLT) due to EA from the time
      between March 2002 and November 2014 at the Liver Transplantation Institute of
      Inonu University. Ten patients (mean age, 38.6 years) undergoing LDLT because of
      unresectable EA were evaluated preoperatively, and the operative and follow-up
      data were analyzed retrospectively. The mean time interval between diagnosis and
      LT was 27 months. The mean operation time and mean intraoperative blood
      requirement were 613 minutes and 4 units of packed red blood cells, respectively.
      Diaphragmatic resections were performed in 3 patients, and vena cava replacement
      was performed in 2 patients because of difficulties in removing the extended
      disease. The local recurrence and distant metastasis rates were 10% and 20%,
      respectively. The mean survival time was 19.5 months (range, 0-54 months), and
      the mortality rate was 30%. Unresectable hepatic alveolar echinococcosis is a
      rare indication for LT and presents some technical difficulties during surgery
      because diaphragmatic resection, vascular reconstruction, or multiple blood
      transfusions may be needed. LDLT can be performed successfully in patients with
      this rare infectious disease, with careful follow-up for potential recurrence and
      metastasis and administration of low-dose immunosuppressive agents.

PMID- 25981333
TI  - The Estrogen Pathway: Estrogen Receptor-alpha, Progesterone Receptor, and
      Estrogen Receptor-beta Expression in Radical Cystectomy Urothelial Cell Carcinoma
      Specimens.
AB  - OBJECTIVE: Bladder cancer has the sixth highest incidence in the United States.
      Treatment of metastatic bladder cancer is difficult, and mortality is certain.
      There are certain pathways in cancer growth and progression that are important in
      bladder cancer development. Recently, the estrogen pathway has been found to be a
      potential target for therapy. METHODS: We identified 410 patients treated with
      radical cystectomy for urothelial cell carcinoma between 1990 and 1994. We
      obtained representative paraffin-embedded tissue blocks for 336 (82.0%) of these
      cases and evaluated the expression and intensity of estrogen receptor (ER)-alpha,
      ER-beta, and progesterone receptor by immunohistochemistry. RESULTS: Among the 12
      ER-alpha-positive cases, median tumor ER-alpha expression was 10% (range, 10%
      50%). In contrast to ER-alpha, all cases were ER-beta-positive. Median tumor ER
      beta expression was 90% (range, 20%-100%). Nearly all cases had ER-beta
      expression of >= 90% (175 [55.9%] with 90% and 103 [32.9%] with 100%). However,
      the intensity of ER-beta staining varied from focal to moderate to marked in 64
      (20.5%), 167 (53.4%), and 82 (26.2%) cases, respectively. Progesterone receptor
      expression was noted to be negative in all cases. CONCLUSIONS: ER-beta is highly
      expressed in bladder cancer. Prospective validation of these data might further
      elucidate the utility of ER-beta as a marker for prognosis or possible target for
      therapy.

PMID- 25981334
TI  - Childhood social inequalities influences neural processes in young adult
      caregiving.
AB  - Childhood poverty is associated with harsh parenting with a risk of transmission
      to the next generation. This prospective study examined the relations between
      childhood poverty and non-parent adults' neural responses to infant cry sounds.
      While no main effects of poverty were revealed in contrasts of infant cry versus
      acoustically matched white noise, a gender by childhood poverty interaction
      emerged. In females, childhood poverty was associated with increased neural
      activations in the posterior insula, striatum, calcarine sulcus, hippocampus, and
      fusiform gyrus, while, in males, childhood poverty was associated with reduced
      levels of neural responses to infant cry in the same regions. Irrespective of
      gender, neural activation in these regions was associated with higher levels of
      annoyance with the cry sound and reduced desire to approach the crying infant.
      The findings suggest gender differences in neural and emotional responses to
      infant cry sounds among young adults growing up in poverty.

PMID- 25981336
TI  - Adropin and apelin fluctuations throughout a season in professional soccer
      players: Are they related with performance?
AB  - Myokines are likely to be involved in the whole-body metabolic adaptive changes
      that occur in response to regular exercise. We aimed to investigate the
      association of the two myokines (adropin and apelin) with physical performance in
      professional soccer players. To this purpose, we analyzed the fluctuations of
      circulating levels of both adropin and apelin in professional soccer players
      during a season and evaluated the possible association of these myokines with the
      performance level. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity
      as well as iron, transferrin and high-sensitivity C-Reactive protein (hsCRP),
      ferritin, soluble transferrin receptor (sTfR), free testosterone/cortisol ratio
      (FTCR), total iron binding capacity (TIBC) were also determined. Fifteen male
      professional soccer players from an Italian Serie A team were included in this
      study. Regarding the results of the biochemical analyses, the patterns of changes
      in the biomarkers of fatigue and inflammation, i.e., HsCRP, CK and LDH reflected
      the effects of the training throughout the season. No significant changes were
      observed in adropin, while apelin exhibited variations that seem not to be
      related with performance. In addition, both adropin and apelin did not represent
      valuable strategy to assist in the performance assessment of professional soccer
      players. 

PMID- 25981335
TI  - Co-expression network of neural-differentiation genes shows specific pattern in
      schizophrenia.
AB  - BACKGROUND: Schizophrenia is a neurodevelopmental disorder with genetic and
      environmental factors contributing to its pathogenesis, although the mechanism is
      unknown due to the difficulties in accessing diseased tissue during human
      neurodevelopment. The aim of this study was to find neuronal differentiation
      genes disrupted in schizophrenia and to evaluate those genes in post-mortem brain
      tissues from schizophrenia cases and controls. METHODS: We analyzed
      differentially expressed genes (DEG), copy number variation (CNV) and
      differential methylation in human induced pluripotent stem cells (hiPSC) derived
      from fibroblasts from one control and one schizophrenia patient and further
      differentiated into neuron (NPC). Expression of the DEG were analyzed with
      microarrays of post-mortem brain tissue (frontal cortex) cohort of 29
      schizophrenia cases and 30 controls. A Weighted Gene Co-expression Network
      Analysis (WGCNA) using the DEG was used to detect clusters of co-expressed genes
      that were non-conserved between adult cases and controls brain samples. RESULTS:
      We identified methylation alterations potentially involved with neuronal
      differentiation in schizophrenia, which displayed an over-representation of genes
      related to chromatin remodeling complex (adjP = 0.04). We found 228 DEG
      associated with neuronal differentiation. These genes were involved with
      metabolic processes, signal transduction, nervous system development, regulation
      of neurogenesis and neuronal differentiation. Between adult brain samples from
      cases and controls there were 233 DEG, with only four genes overlapping with the
      228 DEG, probably because we compared single cell to tissue bulks and more
      importantly, the cells were at different stages of development. The comparison of
      the co-expressed network of the 228 genes in adult brain samples between cases
      and controls revealed a less conserved module enriched for genes associated with
      oxidative stress and negative regulation of cell differentiation. CONCLUSION:
      This study supports the relevance of using cellular approaches to dissect
      molecular aspects of neurogenesis with impact in the schizophrenic brain. We
      showed that, although generated by different approaches, both sets of DEG
      associated to schizophrenia were involved with neocortical development. The
      results add to the hypothesis that critical metabolic changes may be occurring
      during early neurodevelopment influencing faulty development of the brain and
      potentially contributing to further vulnerability to the illness.

PMID- 25981337
TI  - Nanoparticle-based sorting of circulating tumor cells by epithelial antigen
      expression during disease progression in an animal model.
AB  - Circulating tumor cells (CTCs) can be used as markers for the detection,
      characterization, and targeted therapeutic management of cancer. We recently
      developed a nanoparticle-mediated approach for capture and sorting of CTCs based
      on their specific epithelial phenotype. In the current study, we investigate the
      phenotypic transition of tumor cells in an animal model and show the correlation
      of this transition with tumor progression. VX2 tumor cells were injected into
      rabbits, and CTCs were evaluated during tumor progression and correlated with
      computerized tomography (CT) measurements of tumor volume. The results showed a
      dramatic increase of CTCs during the four weeks of tumor growth. Following
      resection, CTC levels dropped but then rebounded, likely due to lymph node
      metastases. Additionally, CTCs showed a marked loss of the epithelial cell
      adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device
      accurately traces disease progression and CTC phenotypic shift in an animal
      model. FROM THE CLINICAL EDITOR: The detection of circulating tumor cells (CTCs)
      has been used to predict disease prognosis. In this study, the authors developed
      a nanoparticle-mediated platform based on microfluidics to analyze the
      differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in
      an animal model. It was found that the loss of EpCAM correlated with disease
      progression. Hence, the use of this platform may be further applied in other
      cancer models in the future.

PMID- 25981338
TI  - Investigation of hydrophobically derivatized hyperbranched polyglycerol with
      PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics.
AB  - We report the synthesis and characterization of a polymeric nanoparticle (NP)
      based on hyperbranched polyglycerol (HPG) containing a hydrophobic core and a
      hydrophilic shell, and assessed its suitability to be developed as a systemic
      anticancer drug carrier. HPG NP displayed low toxicity to primary cell cultures
      and were well-tolerated in mice after intravenous administration. When tested in
      mice tumor xenograft models, HPG NP accumulated significantly in the tumors with
      low accumulation in the liver and the spleen. In vitro studies demonstrated that
      HPG NP was capable of hydrophobically binding docetaxel and releasing it in a
      controlled manner. The HPG NP formulation of docetaxel conferred a preferential
      protective effect on primary non-cancerous cells while effectively killing cancer
      cells, indicating great potential for widening its therapeutic index. Taken
      together, these data indicate that HPG NP is a highly promising nanocarrier
      platform for systemic delivery of anticancer drugs. FROM THE CLINICAL EDITOR: The
      use of polyethylene glycol on nano-carriers as "stealth" to deliver intravenous
      drugs is well known. Here, the authors developed polymeric nanoparticle (NP) with
      hyperbranched polyglycerol (HPG) and tested its efficacy in delivering docetaxel.
      The results showed that this formulation could preferentially killed cancer cells
      with a high therapeutic index. It seems that this platform could have a great
      potential in cancer therapy.

PMID- 25981340
TI  - Influence of fluoro and cyano substituents in the aromatic and antiaromatic
      characteristics of cyclooctatetraene.
AB  - An exhaustive and systematic study of the structural and electronic properties of
      cyclooctatetraene (COT) upon substitution of hydrogen atoms by fluoro and cyano
      groups has been carried out in order to analyse the influence of both
      substituents on the aromaticity. We found that C-C distances decrease with fluoro
      substitution while in cyano derivatives the opposite happens. All the compounds
      retain their original structural type, with the exception of the cyano
      derivatives;thus, compounds 25CN6T, 27CN6T and 30CN8T show boat-like structure,
      whereas compounds 20CN5T, 26CN6T, and 29CN7T present twisted structures.
      Regarding the relative energies of those compounds with the same number of
      substitutions, it was found that compounds where the X groups were more separated
      among them were the most stable ones. Inversion barriers (DeltaETS) were found to
      increase with the number of substitutions; in the case of fluoro derivatives
      these barriers have a two-fold, increase compared to the parent compound while in
      the cyano ones a three-fold increase was observed. The aromatic character based
      on the NICS values, was found to increase in the ground singlet states and in the
      transition states of both fluoro and cyano derivatives. For triplet states, a
      decrease of the aromatic behaviour was found upon substitution. NICS profiles and
      3D NICS isosurfaces confirm such findings. Finally, HOMA indexes corroborate the
      aromatic changes described by the NICS values, although, no good correlations
      between both quantities were found.

PMID- 25981339
TI  - Outcome of Transplantation Using Organs From Donors Infected or Colonized With
      Carbapenem-Resistant Gram-Negative Bacteria.
AB  - Donor-derived infections due to multidrug-resistant bacteria are a growing
      problem in solid organ transplantation, and optimal management options are not
      clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170
      (10.5%) deceased donors with infection or colonization caused by a carbapenem
      resistant gram-negative bacteria that was unknown at the time of transplantation.
      Among them, 14/30 recipients (47%) received a transplant from a donor with
      bacteremia or with infection/colonization of the transplanted organ and were
      considered at high risk of donor-derived infection transmission. The remaining
      16/30 (53%) recipients received an organ from a nonbacteremic donor with
      colonization of a nontransplanted organ and were considered at low risk of
      infection transmission. Proven transmission occurred in 4 of the 14 high-risk
      recipients because donor infection was either not recognized, underestimated, or
      not communicated. These recipients received late, short or inappropriate
      posttransplant antibiotic therapy. Transmission did not occur in high-risk
      recipients who received appropriate and prompt antibiotic therapy for at least 7
      days. The safe use of organs from donors with multidrug-resistant bacteria
      requires intra- and inter-institutional communication to allow appropriate
      management and prompt treatment of recipients in order to avoid transmission of
      infection. 

PMID- 25981341
TI  - Importance of an individual's evaluation of functional status for health-related
      quality of life in patients with multiple sclerosis.
AB  - BACKGROUND: Quantifying the clinical impact of multiple sclerosis (MS) is one of
      the most important determinants for optimizing individual patient care. Useful
      clinical measures for MS can be evaluated from different perspectives.
      OBJECTIVE/HYPOTHESIS: This cross-sectional study compared physical disability and
      functional status as assessed by a neurologist and by a patient and explored how
      they are associated with the health-related quality of life (HRQoL). METHODS: We
      collected data from 223 patients. One neurologist scored functional disability
      using the Kurtzke's Expanded Disability Status Scale (EDSS) and patients
      evaluated their functional status using the Incapacity Status Scale (ISS). HRQoL
      was assessed using the Physical and Mental Component Summary (PCS, MCS) of the
      Short Form-36 Health Survey (SF-36). Multiple linear regressions were applied to
      analyze the data. RESULTS: Total EDSS and ISS scores correlated significantly (r
      = .67; p <= .001). Regression analyses showed that EDSS was significantly related
      to PCS, but not to MCS. After adding ISS into the analysis the association
      between EDSS and PCS became non-significant. ISS contributed significantly to the
      explained variance in both models. The final model explained 49% of the total
      variance for PCS and 15% for MCS. CONCLUSIONS: Functional disability as measured
      by a neurologist (EDSS) is associated with PCS, but not with MCS, whereas
      functional disability as measured by patients (ISS) is significantly associated
      with both HRQoL dimensions. Neurologists should target their attention more on
      patients' evaluations of their functional status in order to detect the most
      bothersome problems that are affecting a patient's quality of life.

PMID- 25981342
TI  - Anti-A and anti-B titers in donor plasma, plasma pools, and immunoglobulin final
      products.
AB  - BACKGROUND: High-dose intravenous immunoglobulin (IVIG) treatments are implicated
      in hemolytic events in some patients receiving treatment. The passive transfer of
      IgG anti-A and anti-B agglutinin is thought to play a role in the development of
      these events. The purpose of this study was to determine the prevalence of high
      titer IgG anti-A and anti-B in plasma donors and investigate if there is any
      advantage of excluding these donors from the donor pool to limit anti-A and anti
      B content in IVIG product. STUDY DESIGN AND METHODS: IgG anti-A and anti-B levels
      were assessed from group O donor plasma, manufacturing IgG plasma pools, and
      finished IVIG product (Gammagard Liquid). Antibody level in group O donors was
      also assessed by sex and age for their relative contribution of antibody to the
      plasma pool. RESULTS: The majority of group O donors (80%) had antibody titers of
      less than 1000. Of those with titers of at least 1000, theoretical estimates
      provide further evidence that the effects of high-titer donors are minimal.
      Antibody levels in plasma pools both during the manufacturing process and from
      the final IVIG product also support that anti-A and anti-B levels are low. In
      general, there were more females than males with higher antibody titer levels,
      with significantly more females than males with anti-A. CONCLUSION: Excluding
      donors with high anti-A and anti-B titers has minimal impact on the finished IVIG
      product titers due to ABO antibody neutralization and the dilution factor in the
      manufacturing pool.

PMID- 25981344
TI  - Grooming using rotating brushes as a proactive method to control ship hull
      fouling.
AB  - Grooming may be defined as the frequent and gentle cleaning of a ship hull
      coating, when it is in port or idle, to prevent the establishment of fouling.
      This study assessed the effectiveness of grooming with a five-headed rotating
      brush system on epoxy, ablative copper and two silicone fouling release (FR)
      coatings. These coatings were placed under static immersion at Port Canaveral, FL
      on a weekly and biweekly frequency. The results showed that grooming reduced
      fouling on all surfaces and was able to prevent fouling on the ablative copper
      and FR coatings when performed weekly. It was concluded that the grooming tool
      used for these tests was sufficient to remove biofilm and most hard fouling.
      However, when fouling pressure increased or when grooming was performed less
      frequently, insufficient forces were imparted by the brush to remove all of the
      established hard fouling organisms. 

PMID- 25981343
TI  - Experimental O-space turbo spin echo imaging.
AB  - PURPOSE: Turbo spin echo (TSE) imaging reduces imaging time by acquiring multiple
      echoes per repetition (TR), requiring fewer TRs. O-space can also require fewer
      TRs by using a combination of nonlinear magnetic gradient fields and surface coil
      arrays. Although to date, O-space has only been demonstrated for gradient echo
      imaging, it is valuable to combine these two techniques. However, collecting
      multiple O-space echoes per TR is difficult because of the different local k
      space trajectories and variable T2-weighting. THEORY AND METHODS: A practical
      scheme is demonstrated to combine the benefits of TSE and O-space for highly
      accelerated T2-weighted images. The scheme uses a modified acquisition order and
      filtered projection reconstruction to reduce artifacts caused by T2 decay, while
      retaining T2 contrast that corresponds to a specific echo time. RESULTS: The
      experiments revealed that the proposed method can produce highly accelerated T2
      weighted images. Moreover, the method can generate multiple images with different
      T2 contrasts from a single dataset. CONCLUSIONS: The proposed O-space TSE imaging
      method requires fewer echoes than conventional TSE and fewer repetitions than
      conventional O-space imaging. It retains resilience to undersampling, clearly
      outperforming Cartesian SENSE at high levels of undersampling, and can generate
      undistorted images with a range of T2 contrast from a single acquired dataset.

PMID- 25981345
TI  - Temporomandibular joint vibrations from totally asymptomatic subjects.
AB  - OBJECTIVE: Precisely characterize the TMJ vibrations of a youthful, adult and
      completely asymptomatic population. METHODS: TMJ vibrations were recorded from
      237 asymptomatic subjects (163 f, 74 m) at Dayananda Sagar Institute in India.
      The subjects were selected, examined and informed (WMA Helsinki Declaration). TMJ
      vibrations were recorded bilaterally during maximal open - close. 6 parameters of
      the vibrations were analyzed between the left and right sides, between genders
      and with respect to age. RESULTS: Mean vibration intensity was greater for
      females (p < 0.01) than males. A portion of the frequency spectrum < 300 Hz was
      also more intense for females (p < 0.022). Females 18 - 20 years old exhibited
      higher Peak Amplitude than 27 - 30 year olds (p < 0.025) and lower Median
      Frequency (p < 0.005). CONCLUSIONS: A significant difference in TMJ vibrations
      was present between males and females, increased with age in females but not in
      males.

PMID- 25981346
TI  - Chemical analysis of Karenia papilionacea.
AB  - One of the most widely studied organisms responsible for Harmful Algal Blooms
      (HABs) is the marine dinoflagellate Karenia brevis. This organism produces
      neurotoxic compounds known as brevetoxins. A related dinoflagellate, Karenia
      papilionacea, has been reported to occasionally co-bloom with K. brevis but has
      received little attention as a possible toxin producing species. Therefore, our
      aim was to investigate the toxin profile for K. papilionacea. A toxic fraction
      was identified using a cell based cytotoxicity assay and the toxin was isolated
      and identified as the ladder frame polyether brevetoxin-2 (PbTx-2) using mass
      spectrometry (MS) and nuclear magnetic resonance (NMR). Toxin production in K.
      papilionacea increased in response to hypoosmotic stress, as previously observed
      in K. brevis. 

PMID- 25981347
TI  - Influence of age on the absorption, metabolism, and excretion of cocoa flavanols
      in healthy subjects.
AB  - SCOPE: An understanding of the pharmacokinetics of structurally related (-)
      epicatechin metabolites (SREM) is a prerequisite for considering cocoa flavanols
      (CF) in the context of dietary recommendations. The objective of this study was
      to compare the absorption, metabolism, and excretion of SREM in healthy young and
      elderly Caucasian men. METHODS AND RESULTS: Intraindividual variability of SREM
      was assessed in seven young subjects, after consuming 10.7 mg CF/kg body weight
      (BW) on two occasions separated by 1 week. The effect of age on flavanols ADME
      was assessed in 20 young (18-35 years) and 20 elderly (65-80 years) healthy male
      subjects receiving 5.3 and 10.7 mg total CF/kg BW or 1 g of acetaminophen as a
      control to compare differences in Phase II metabolism on three days separated by
      1 week of wash-out. Blood and urine samples were collected for 24-h post
      consumption. The intraindividual variation, measured as CV(%) with respect to the
      area-under-the-curve of the concentration over time (AUC(0-6h) ) of SREM, was
      16%, while the interindividual variation in AUC(0-6h) , was 38%, comparable to
      acetaminophen (39%). The AUC(0-6h) and the 24-h excretion of total SREM was not
      significantly different between young and elderly subjects. At the high intake
      amount, the AUC(0-6h) of (-)-epicatechin-3'-beta-D-glucuronide was greater in
      elderly subjects, whereas the AUC(0-6h) of 3'-O-methyl-(-)-epicatechin-5-sulfate
      and 3'-O-methyl-(-)-epicatechin-7-sulfate as well as the 24-h urinary excretion
      of gamma-valerolactone metabolites were lower in the elderly. CONCLUSION: Cocoa
      flavanols are absorbed, metabolized, and excreted in healthy young and elderly
      subjects with relatively small differences between the two groups.

PMID- 25981348
TI  - Adjunctive aripiprazole in the treatment of risperidone-induced
      hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response
      study.
AB  - Hyperprolactinemia is an unwanted adverse effect associated with several
      antipsychotics. The addition of partial dopamine receptor agonist aripiprazole
      may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the
      ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose
      effects of adjunctive treatment with aripiprazole on prolactin levels and
      hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old
      with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20
      ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or
      oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to
      fixed dose risperidone treatment. Serum prolactin levels were measured at
      baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were
      assessed at baseline and week 8 using the Positive and Negative Syndrome Scale,
      Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus
      Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%)
      completed the 8-week study. At study end, all three aripiprazole doses resulted
      in significantly lower prolactin levels (beginning at week 2), higher response
      rates (>=30% prolactin reduction) and higher prolactin normalization rates than
      placebo. Effects were significantly greater in the 10 and 20mg/day groups than
      the 5mg/day group. No significant changes were observed in any treatment groups
      regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole
      treatment was effective and safe for resolving risperidone-induced
      hyperprolactinemia, producing significant and almost maximal improvements by week
      2 without significant effects on psychopathology and side effects.

PMID- 25981350
TI  - Cord blood IgE: fetal or maternal?

PMID- 25981351
TI  - Classification of angioedema by endotypes.

PMID- 25981353
TI  - Condensate microdrop self-propelling aluminum surfaces based on controllable
      fabrication of alumina rod-capped nanopores.
AB  - Here, we report a type of aluminum-based condensate microdrop self-propelling
      (CMDSP) functional films based on the controllable fabrication of anodic alumina
      rod-capped nanopores, which can be realized by a three-step method based on the
      skillful combinations of well-established hard anodization, mild anodization and
      chemical etching techniques. Such a surface nanoengineering strategy is verified
      to be feasible via our exemplified experiments and scanning electronic microscopy
      characterizations. After fluorosilane modification, the surface nanostructure can
      induce the efficient self-jumping of small-scale condensate microdrops,
      especially below 50 MUm. This work offers an avenue for developing CMDSP aluminum
      surfaces with self-cleaning, antifrosting, and antidewing functions. 

PMID- 25981354
TI  - Effects of weight loss diet therapy on anthropometric measurements and
      biochemical variables in schizophrenic patients.
AB  - BACKGROUND: Prevalence of obesity in schizophrenic patients is two to three times
      higher than in the general population and unhealthy dietary patterns, a sedentary
      lifestyle and antipsychotic medication use may contribute to the higher levels of
      obesity among schizophrenic patients. AIMS: We evaluated the effects of diet
      therapy on weight loss, anthropometric and biochemical variables in overweight or
      obese (body mass index, BMI >= 27 kg/m(2)) female schizophrenic patients who use
      antipsychotic medications and in healthy volunteers. METHODS: Primary demographic
      variables were collected via questionnaire; blood samples and anthropometric
      measurements were obtained. Personalized diet recipes were prepared and
      nutritional education was shared. We logged the physical activity of the patients
      and maintained food consumption records at 3-day intervals. Participants were
      weighed every week; anthropometric measurements and blood samples were collected
      at the end of the first and second months. RESULTS: At the end of the study,
      reductions in body weight and other anthropometric measurements were
      statistically significant (P < 0.05). Reductions in body weight and BMI values
      for patient group were - 4.05 +/- 1.73 kg and - 1.62 +/- 0.73 kg/m(2) and for the
      control group were - 6.79 +/- 1.80 kg and - 2.55 +/- 0.64 kg/m(2), respectively.
      When compared with the patient group, reductions in the anthropometric variables
      of the control group were statistically significant (P < 0.05). Fasting glucose,
      blood lipids, albumin and leptin levels were decreased; insulin and homeostatic
      model assessment-measured insulin resistance (HOMA-IR) levels were increased
      insignificantly. Increases in the blood ghrelin levels for both groups were
      statistically significant (P < 0.05). CONCLUSIONS: Improvements to the diets of
      schizophrenic patient led to improvements in anthropometric measurements and
      biochemical variables and reduced the health risks caused by antipsychotic
      medications. Furthermore, we hypothesize that antipsychotic medications do not
      have any direct effect on leptin and ghrelin metabolism, and that changes in
      hormone metabolism may be attributable to changes in body weight.

PMID- 25981355
TI  - Color-Coded Imaging of Breast Cancer Metastatic Niche Formation in Nude Mice.
AB  - We report here a color-coded imaging model in which metastatic niches in the lung
      and liver of breast cancer can be identified. The transgenic green fluorescent
      protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse
      expresses GFP in all organs. However, GFP expression is dim in the liver
      parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red
      fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to
      produce experimental lung metastasis and in the spleen of GFP nude mice to
      establish a liver metastasis model. Niche formation in the lung and liver
      metastasis was observed using very high resolution imaging systems. In the lung,
      GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In
      addition, GFP host cells were observed to form circle-shaped niches in the lung
      even without RFP cancer cells, which was possibly a niche in which future
      metastasis could be formed. In the liver, as with the lung, GFP host cells could
      form circle-shaped niches. Liver and lung metastases were removed surgically and
      cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated
      fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as
      a metastatic niche.

PMID- 25981356
TI  - Modulation of cell morphogenesis by tousled-like kinase in the Drosophila
      follicle cell.
AB  - BACKGROUND: Tousled-like kinase (Tlk) is a conserved serine/threonine kinase
      regulating DNA replication, chromatin assembly, and DNA repair. Previous studies
      have suggested that Tlk is involved in cell morphogenesis in vitro. In addition,
      tlk genetically interact with Rho1, which encodes a key regulator of the
      cytoskeleton. However, whether Tlk plays a physiological role in cell
      morphogenesis and cytoskeleton rearrangement remains unknown. RESULTS: In tlk
      mutant follicle cells, area of the apical domain was reduced. The density of
      microtubules was increased in tlk mutant cells. The density of actin filaments
      was increased in the apical region and decreased in the basal region. Because
      area of the apical domain was reduced, we examined the levels of proteins located
      in the apical region by using immunofluorescence. The fluorescence intensities of
      two adherens junction proteins Armadillo (Arm) and DE-cadherin (DE-cad), atypical
      protein kinase C (aPKC), and Notch, were all increased in tlk mutant cells. The
      basolateral localized Discs large (Dlg) shifted apically in tlk mutant cells.
      CONCLUSIONS: Increase of protein densities in the apical region might be resulted
      from disruption of the cytoskeleton and shrinkage of the apical domain. Together,
      these data suggest a novel role of Tlk in maintaining cell morphology, possibly
      through modulating the cytoskeleton.

PMID- 25981358
TI  - Microalbuminuria and prediction of cardiovascular complications in patients with
      coronary artery disease and type 2 diabetes mellitus after CABG surgery.
AB  - BACKGROUND: This investigation was aimed at assessing the clinical significance
      of microalbuminuria (MA) in predicting in-hospital adverse outcomes amongst the
      patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who
      have undergone coronary artery bypass graft (CABG) surgery. METHODS: We recruited
      720 consecutive Caucasian (Russian) patients who underwent CABG surgery during
      2011-2012. RESULTS: Patients with renal dysfunction (RD) and without type 2 DM
      had significantly higher median serum creatinine seven days after CABG surgery
      compared to patients without RD and type 2 DM. There were no statistically
      significant intergroup differences regarding glomerular filtration rate. However,
      the highest median of urine albumin excretion 24hours before and seven days after
      CABG surgery was detected in patients with RD and type 2 DM whilst the lowest
      median was noted in patients without RD and type 2 DM. Median of urine albumin
      excretion 24hours before and seven days after CABG surgery in patients with
      adverse outcome was significantly higher compared to patients with a favourable
      outcome. CONCLUSIONS: We suggest that the determination of MA before and after
      CABG surgery may assist in predicting adverse outcomes after CABG surgery.

PMID- 25981357
TI  - Alternatively activated macrophages promote pancreatic fibrosis in chronic
      pancreatitis.
AB  - Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and
      fibrotic disease with no cure. Unlike acute pancreatitis (AP), we find that
      alternatively activated macrophages (AAMs) are dominant in mouse and human CP.
      AAMs are dependent on interleukin (IL)-4 and IL-13 signalling, and we show that
      mice lacking IL-4Ralpha, myeloid-specific IL-4Ralpha and IL-4/IL-13 were less
      susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and
      human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we
      show that pharmacologic inhibition of IL-4/IL-13 in human ex vivo studies as well
      as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a
      critical role for macrophages in pancreatic fibrosis and in turn PSCs as
      important inducers of macrophage-alternative activation. Our study challenges and
      identifies pathways involved in crosstalk between macrophages and PSCs that can
      be targeted to reverse or halt pancreatic fibrosis progression. 

PMID- 25981359
TI  - Is Previous Cardiac Surgery a Risk Factor for Short and Mid-term Mortality
      Following Total Aortic Arch Replacement in Patients with Stanford Type A Aortic
      Dissection?
AB  - BACKGROUND: The aim of this study was to evaluate if the previous cardiac surgery
      (PCS) is the risk factor for short- and mid-term mortality following total aortic
      arch replacement in patients with Stanford type A aortic dissection. METHODS:
      Between February 2009 and February 2012, a total of 384 patients who suffered
      Stanford type A aortic dissection involving aortic arch underwent total aortic
      arch replacement with frozen elephant trunk. Of these patients, 36 patients had
      PCS. Logistic regression was used to identify if the previous cardiac surgery was
      the risk factor for in-hospital mortality. Propensity score-matching (1:1 match)
      was used to yield patients from the primary surgery group who matched PCS group
      with respect to pre-operative clinical characteristics and post-operative
      complications. Survival analysis and differences between the two groups were
      performed by the Kaplan-Meier estimate and the log-rank test. RESULTS: The
      overall in-hospital mortality was 8%. Logistic multiple regression identified
      that cardiopulmonary bypass time>= 300minutes (OR=12.05, p<0.001) and surgical
      period from symptom onset shorter than one week (OR=2.43, p=0.04) were final risk
      factors for in-hospital mortality and PCS was not the final risk factor. Of 36
      patients with PCS, three patients died in the hospital and 33 patients were
      discharged from the hospital. Of these 33 patients, 32 patients matched primary
      surgery group successfully. During the follow-up period, two patients died in PCS
      group, one patient died in primary surgery group. The mean follow-up time was
      35.38+/-14.12 months. The five-year survival was 96% for the primary surgery
      group. Previous cardiac surgery group five-year survival was 73%. Five-year
      survival was not significantly different between the two groups (p=0.84 log-rank
      test). CONCLUSIONS: PCS is not the risk factor for short- and mid-term mortality
      following total aortic arch replacement in patients with Stanford type A aortic
      dissection.

PMID- 25981360
TI  - Metabolic syndrome in female migraine patients is associated with medication
      overuse headache: a clinic-based study in China.
AB  - BACKGROUND AND PURPOSE: Migraine and metabolic syndrome have been reported to
      coexist to a marked degree, especially in women migraine patients, but the
      relationship between these two conditions is still unclear. This study was
      performed to evaluate the association of headache characteristics and its
      comorbidities with metabolic syndrome (MetS) and its components in female
      migraine patients. METHODS: A total of 142 women with migraine who fulfilled the
      criteria of the International Classification of Headache Disorders 2nd edition
      were recruited in a neurological outpatient department in China. The
      characteristics of migraine and its comorbidities (analgesic use, psychiatric
      disorders and disability) were assessed with a detailed questionnaire.
      Anthropometrics, blood biochemistry and transcranial Doppler sonography were used
      for metabolic measurements and vascular function. RESULTS: Of 142 participants,
      70.4% had one or more metabolic abnormalities and 12.0% had MetS. After
      adjustment for age, residence, body mass index, waist-to-height ratio, smoking
      and drinking history, chronic migraine in women patients was associated with MetS
      [odds ratio (OR) = 5.342, P = 0.032], but when the chronic migraine patients were
      comorbid with medication overuse headache (MOH), the risk for MetS increased
      significantly (OR = 12.68, P = 0.007). In addition, MOH was associated with
      abdominal obesity and hypertension amongst the components of MetS (OR = 4.205 and
      3.234, P = 0.043 and 0.039, respectively). CONCLUSIONS: Our study may suggest
      that chronic migraine is associated with MetS, especially when it is comorbid
      with analgesic overuse. MOH may be the risk factor for MetS in female migraine
      patients and associated with abdominal obesity and hypertension.

PMID- 25981361
TI  - The pathogenesis of reversible T-wave inversions or large upright peaked T-waves:
      Sympathetic T-waves.
AB  - Reversible electrocardiographic (ECG) repolarization changes including T-wave
      inversions (TWI), large upright peaked T-waves (LUPTW) and prolongation of the
      corrected QT interval (P-QTc) have been reported in association with myriads of
      acute cardiac and non-cardiac diseases. Through the last 70 years, the TWIs have
      been described under different terms as; cerebral, giant, global, canyon, Wellens
      or coronary and cardiac memory T waves. During the last 15 years, the reversible
      TWI and LUPTW in association with P-QTc have been described as characteristic ECG
      features in takotsubo syndrome (TS), which also may be triggered by the same
      aforementioned acute cardiac and non-cardiac disease entities. The pathogenesis
      of these reversible T-wave changes is not clear-cut. In this manuscript,
      substantial evidences for a causal link between the local cardiac sympathetic
      disruption and the development of the reversible TWI and LUPTW are presented. As
      a result, a pathogenetic term for the reversible TWI or LUPTW, which is
      sympathetic T waves (sympathetic TWI or sympathetic LUPTW), would be the most
      appropriate term.

PMID- 25981362
TI  - Radial strength and expansion of scaffold struts remain a concern when
      considering a PCI with bioresorbable vascular scaffold.

PMID- 25981364
TI  - Rivaroxaban-induced liver injury: Results from a venous thromboembolism registry.

PMID- 25981363
TI  - The patient perspective: Quality of life in advanced heart failure with frequent
      hospitalisations.
AB  - End of life is an unfortunate but inevitable phase of the heart failure patients'
      journey. It is often preceded by a stage in the progression of heart failure
      defined as advanced heart failure, and characterised by poor quality of life and
      frequent hospitalisations. In clinical practice, the efficacy of treatments for
      advanced heart failure is often assessed by parameters such as clinical status,
      haemodynamics, neurohormonal status, and echo/MRI indices. From the patients'
      perspective, however, quality-of-life-related parameters, such as functional
      capacity, exercise performance, psychological status, and frequency of re
      hospitalisations, are more significant. The effects of therapies and
      interventions on these parameters are, however, underrepresented in clinical
      trials targeted to assess advanced heart failure treatment efficacy, and data are
      overall scarce. This is possibly due to a non-universal definition of the quality
      of-life-related endpoints, and to the difficult standardisation of the data
      collection. These uncertainties also lead to difficulties in handling trade-off
      decisions between quality of life and survival by patients, families and
      healthcare providers. A panel of 34 experts in the field of cardiology and
      intensive cardiac care from 21 countries around the world convened for reviewing
      the existing data on quality-of-life in patients with advanced heart failure,
      discussing and reaching a consensus on the validity and significance of quality
      of-life assessment methods. Gaps in routine care and research, which should be
      addressed, were identified. Finally, published data on the effects of current
      i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on
      quality-of-life in advanced heart failure patients were analysed. 

PMID- 25981365
TI  - Authors' reply to rosuvastatin and risk of acute pancreatitis.

PMID- 25981366
TI  - DEFEAT-HF Trial: The potential causes for the negative result.

PMID- 25981367
TI  - The SHARPEN clinical risk score predicts mortality in patients with infective
      endocarditis: An 11-year study.

PMID- 25981368
TI  - Successful transcatheter closure of residual ventriculopulmonary blood flow with
      muscular VSD occluder after ligation of pulmonary trunk in Fontan procedure.

PMID- 25981369
TI  - Association of wall shear stress with long-term vascular healing response
      following bioresorbable vascular scaffold implantation.

PMID- 25981370
TI  - Value of pericardial effusion as imaging biomarker in acute pericarditis, do we
      need to focus on more appropriate ones?

PMID- 25981371
TI  - Improvement in left ventricular ejection fraction and reverse remodeling in
      elderly heart failure patients on intense NT-proBNP-guided therapy.
AB  - BACKGROUND: In chronic heart failure, left ventricular ejection fraction (LVEF)
      is considered to be stable. Intensified therapy may improve survival, but little
      is known whether this is associated with reverse remodeling and dependent on age
      and NT-proBNP guidance. We aimed to define the evolution of LVEF under
      intensified therapy in relation to age and NT-proBNP guidance. METHODS AND
      RESULTS: Echocardiography was performed at baseline, 12 and 18months in TIME-CHF,
      a trial comparing NT-proBNP versus symptom-guided therapy in patients aged 60 to
      74 and >=75 years. LVEF, LV end diastolic volume index (LVEDVI) and end systolic
      volume index (LVESVI) were assessed. LVEF increased from 31.3 +/- 10.7% to 39.1+/
      11.8% at 18 months (p<0.001) in symptom-guided, and from 30.3 +/- 11.7% to 44.0
      +/- 13.2% (p<0.001) in NT-proBNP-guided patients. The increase in LVEF was
      significantly larger in the NT-proBNP-guided treatment group (p for
      interaction=0.006), which was true for both age groups (p for interaction in
      both=0.091). LVEDVI and LVESVI decreased without influence by study group
      allocation. CONCLUSIONS: In elderly heart failure patients, intensified medical
      therapy leads to an improvement in LVEF and to reverse remodeling. NT-proBNP
      guided therapy was associated with a larger improvement in LVEF than symptom
      guided therapy both in patients aged 60 to 74 and >=75 years. TRIAL REGISTRATION:
      http://isrctn.org Identifier: ISRCTN43596477.

PMID- 25981372
TI  - The duodenal glucose load impacts the oral disposition index in healthy subjects.
AB  - AIM: In healthy subjects, the oral disposition index (ratio of insulin response
      to insulin sensitivity) is predictive of the development of Type 2 diabetes.
      Gastric emptying, which exhibits a substantial interindividual variation, is a
      major determinant of postprandial glycaemia in health and diabetes. We sought to
      determine whether the rate of intraduodenal glucose delivery affects the
      disposition index in people without diabetes. METHODS: Nineteen Caucasian males
      received glucose infusions via an intraduodenal catheter at either 2 kcal/min
      (ID2) or 4 kcal/min (ID4) for 120 min, on two separate days with measurements of
      blood glucose (G) and plasma insulin (I) at frequent intervals. The insulin
      response was estimated by the ratio of the change in insulin to that of change in
      glucose at 30 min (?I(0-30)/?G(0-30)) and 60 min (?I(0-60)/?G(0-60)). Insulin
      sensitivity was estimated as 1/fasting insulin. The oral disposition index (DI)
      was calculated as ?I(0-30)/?G(0-30) * 1/fasting insulin and ?I(0-60)/?G(0-60) *
      1/fasting insulin. RESULTS: The overall glycaemic response was comparable on both
      days, but the insulin response was much greater at ID4 when calculated at either
      30 or 60 min (P < 0.05). DI was also greater (P < 0.05) in response to ID4 than
      ID2. CONCLUSIONS: The rate of duodenal glucose delivery has a major impact on
      insulin release and, thereby, DI. This suggests that the rate of gastric
      emptying, which determines duodenal glucose delivery, is a determinant of DI.

PMID- 25981373
TI  - Nrf2 deficiency causes lipid oxidation, inflammation, and matrix-protease
      expression in DHA-supplemented and UVA-irradiated skin fibroblasts.
AB  - Fish oil rich in docosahexaenoic acid (DHA) has beneficial effects on human
      health. Omega-3 polyunsaturated fatty acids are precursors of eicosanoids and
      docosanoids, signaling molecules that control inflammation and immunity, and
      their dietary uptake improves a range of disorders including cardiovascular
      diseases, ulcerative colitis, rheumatoid arthritis, and psoriasis. The
      unsaturated nature of these fatty acids, however, makes them prone to oxidation,
      especially when they are incorporated into (membrane) phospholipids. The skin is
      an organ strongly exposed to oxidative stress, mainly due to solar ultraviolet
      radiation. Thus, increased levels of PUFA in combination with oxidative stress
      could cause increased local generation of oxidized lipids, whose action spectrum
      reaches from signaling molecules to reactive carbonyl compounds that can
      crosslink biomolecules. Here, we investigated whether PUFA supplements to
      fibroblasts are incorporated into membrane phospholipids and whether an increase
      of PUFA within phospholipids affects the responses of the cells to UV exposure.
      The redox-sensitive transcription factor Nrf2 is the major regulator of the
      fibroblast stress response to ultraviolet radiation or exposure to oxidized
      lipids. Here we addressed how Nrf2 signaling would be affected in PUFA
      supplemented human dermal fibroblasts and mouse dermal fibroblasts from Nrf2
      deficient and wild type mice. We found, using HPLC-tandem MS, that DHA
      supplements to culture media of human and murine fibroblasts were readily
      incorporated into phospholipids and that subsequent irradiation of the
      supplemented cells with UVA resulted in an increase in 1-palmitoyl-2
      (epoxyisoprostane-E2)-sn-glycero-3-phosphorylcholine and Oxo-DHA esterified to
      phospholipid, both of which are Nrf2 agonists. Also, induction of Nrf2 target
      genes was enhanced in the DHA-supplemented fibroblasts after UVA irradiation. In
      Nrf2-deficient murine fibroblasts, the expression of the target genes was, as
      expected, decreased, but surprisingly, expression of TNFalpha and MMP13 was
      strongly induced in DHA-supplemented, UVA-irradiated cells. Also, Nrf2-deficient
      cells had increased levels of oxidized phospholipids relative to the unoxidized
      precursors after UVA irradiation. Our data suggest that under ultraviolet stress
      a functioning Nrf2 system is required to prevent DHA-induced inflammation and
      matrix degradation in dermal fibroblasts. 

PMID- 25981374
TI  - Cutaneous Penile Horn.
AB  - A 70-year-old man presented with a slowly enlarging glans penis lesion measuring
      approximately 3 * 2 * 2 cm. On examination, the lesion was indurated with no
      induration of the glans penis deep to the lesion. He had no palpable
      lymphadenopathy. A glans sparing surgical excision was performed. Pathology
      demonstrated a squamoproliferative lesion with hyperkeratosis, and deep margin
      biopsy demonstrated no carcinoma. Cutaneous penile horns are hyperkeratotic
      lesions and may be associated with synchronous or metachronous squamous cell
      carcinoma. Surgical excision remains the mainstay of treatment, and follow-up
      physical examinations to assess for metachronous penile carcinoma are
      recommended.

PMID- 25981375
TI  - Re: Park et al.: The Presence of Chlamydia Is Associated With Increased Leukocyte
      Counts and Pain Severity in Men With Chronic Pelvic Pain Syndrome (Urology
      2015;85:574-579).

PMID- 25981376
TI  - Reply by the Authors.

PMID- 25981377
TI  - Utility of the auditory brainstem response evaluation in non-clinical drug safety
      evaluations.
AB  - INTRODUCTION: The Food and Drug Administration (FDA) requires thorough evaluation
      of the potential safety hazards of all new drugs, food additives, and therapeutic
      devices that are intended for human use. Drugs that are otically administered
      (i.e., ear drops), or are known to systemically distribute to the inner ear,
      require additional specialized safety testing to ensure that the drug does not
      permanently impair auditory function. METHODS: To properly determine a drug's
      impact on auditory function, the FDA's Center for Drug Evaluation and Research
      requires the use of the Auditory Brainstem Response (ABR) evaluation. The ABR
      evaluation uses auditory stimuli evoked potentials to assess function by
      establishing minimum intensity thresholds. These thresholds can be monitored
      following drug treatment to determine an impact on hearing loss. This review
      discusses methodical considerations for conducting ABR evaluations as they apply
      to specialized drug safety studies. Alternative assays are discussed and compared
      to the utility of the ABR evaluation. CONCLUSIONS: The ABR evaluation provides
      reliable and sensitive measures of hearing function that are suitable for
      definitive drug safety evaluations or hazardous risk assessments.

PMID- 25981378
TI  - Benevolent Images of God, Gratitude, and Physical Health Status.
AB  - This study has two goals. The first is to assess whether a benevolent image of
      God is associated with better physical health. The second goal is to examine the
      aspects of congregational life that is associated with a benevolent image of God.
      Data from a new nationwide survey (N = 1774) are used to test the following core
      hypotheses: (1) people who attend worship services more often and individuals who
      receive more spiritual support from fellow church members (i.e., informal
      assistance that is intended to increase the religious beliefs and behaviors of
      the recipient) will have more benevolent images of God, (2) individuals who
      believe that God is benevolent will feel more grateful to God, (3) study
      participants who are more grateful to God will be more hopeful about the future,
      and (4) greater hope will be associated with better health. The data provide
      support for each of these relationships. 

PMID- 25981380
TI  - Effectiveness of chemotherapy and radiotherapy for laryngeal preservation in
      advanced laryngeal cancer: a meta-analysis and systematic review.
AB  - PURPOSE: This meta-analysis compared the efficacy of laryngectomy and three
      larynx-preservation treatments in patients with advanced laryngeal cancer.
      MATERIALS AND METHODS: Medline, Cochrane, EMBASE and Google Scholar databases
      were searched (until May 5, 2014) for studies that evaluated total laryngectomy
      followed by radiation and three larynx-preserving strategies in patients with
      advanced laryngeal cancer. The outcomes assessed were the 2- to 5-year overall
      survival (OS), disease-free survival (DFS), and laryngectomy-free survival (LFS)
      RESULTS: The search identified ten studies which were used for the meta-analysis
      (N = 2013 patients). The meta-analysis found that among different treatments, RT
      alone was associated with the highest rate of OS (71.6 %), DFS (57.8 %), and LFS
      (79.0 %). OS was similar among the following treatments: laryngectomy->RT vs. CT
      >RT [P = 0.402]; RT+CT vs. RT alone [P = 0.440]; and RT+CT vs CT->RT [P = 0.588].
      DFS rate was higher in patients receiving laryngectomy->RT than CT->RT (P =
      0.001) and was similar for RT+CT compared with CT->RT (P = 0.590). CONCLUSION:
      These findings suggest that of the larynx-preserving treatments, RT alone was
      associated with highest rates of OS, DFS, and LFS in patients with locally
      advanced cancer of the larynx and hypopharynx. Laryngectomy provided a better
      rate of DFS than CT and RT, but OS were similar across the different larynx
      preserving treatments and laryngectomy.

PMID- 25981379
TI  - Dose levels and image quality of second-generation 128-slice dual-source coronary
      CT angiography in clinical routine.
AB  - OBJECTIVES: To compare radiation exposure and image quality of second-generation
      128-slice dual-source CT (DSCT) coronary angiography (cCTA) protocols. MATERIALS
      AND METHODS: We retrospectively analyzed data from four groups with 25 patients,
      each examined by one of the following DSCT cCTA protocols: prospectively ECG
      gated high-pitch (group 1) or sequential (group 2) acquisition, retrospectively
      ECG-gated acquisition in dual-energy (DECT, group 3) or dual-source (group 4)
      mode. CT dose index volume, dose length product, estimated radiation dose,
      contrast-to-noise- and signal-to-noise-ratios were compared. Subjective image
      quality was rated by two observers blinded to the protocols. RESULTS: High-pitch
      DSCT showed a mean estimated radiation dose of 1.27 +/- 0.62 mSv, significantly
      (p < 0.01) lower than sequential (2.04 +/- 0.94 mSv), dual-energy (3.97 +/- 1.29
      mSv) or dual-source (8.11 +/- 4.95 mSv) acquisition. Image noise showed no
      statistical difference (p > 0.91), ranging from 15.2 +/- 4.4 (group 2) up to 24.5
      +/- 22.0 (group 4). Each protocol showed diagnostic image quality in at least
      98.1 % of evaluated coronary segments without significant differences (p > 0.05).
      CONCLUSIONS: Prospectively ECG-gated DSCT protocols enable cCTA with significant
      dose reduction and consistently diagnostic image quality. In patients requiring
      retrospectively ECG-gated DSCT for functional analysis or due to arrhythmia, dual
      energy mode should be preferred over dual-source mode as it significantly
      decreases estimated dose without compromising image quality.

PMID- 25981381
TI  - Collateral non cardiac findings in clinical routine CT coronary angiography:
      results from a multi-center registry.
AB  - PURPOSE: The aim of the study was to evaluate the prevalence of collateral
      findings detected in computed tomography coronary angiography (CTCA) in a multi
      center registry. MATERIALS AND METHODS: We performed a retrospective review of
      4303 patients (2719 males, mean age 60.3 +/- 10.2 years) undergoing 64-slice CTCA
      for suspected or known coronary artery disease (CAD) at various academic
      institutions between 01/2006 and 09/2010. Collateral findings were recorded and
      scored as: non-significant (no signs of relevant pathology, not necessary to be
      reported), significant (clear signs of pathology, mandatory to be reported), or
      major (remarkable pathology, mandatory to be reported and further investigated).
      RESULTS: We detected 6886 non-cardiac findings (1.6 non cardiac finding per
      patient). Considering all centers, only 865/4303 (20.1 %) patients were
      completely without any additional finding. Overall, 2095 (30.4 %) non
      significant, 4486 (65.2 %) significant, and 305 (4.4 %) major findings were
      detected. Among major findings, primary lung cancer was reported in 21 cases. In
      every center, most prevalent significant findings were mediastinal lymph nodes >1
      cm. In 256 patients, collateral findings were clinically more relevant than
      coexisting CAD and justified the symptoms of patients. CONCLUSIONS: The
      prevalence of significant and major collateral findings in CTCA is high.
      Radiologists should carefully evaluate the entire scan volume in each patient.

PMID- 25981382
TI  - Reliability of frontal sinus by cone beam-computed tomography (CBCT) for
      individual identification.
AB  - Analysis of the frontal sinus is an important tool in personal identification.
      Cone beam-computed tomography (CBCT) is also progressively replacing conventional
      radiography and multi-slice computed tomography (MSCT) in human identification.
      The aim of this study is to develop a reproducible technique and measurements
      from 3D reconstructions obtained with CBCT, for use in human identification. CBCT
      from 150 patients (91 female, 59 male), aged between 15 and 78 years, was
      analysed with the specific software program MIMICS 11.11 (Materialise N.V.,
      Leuven, Belgium). Corresponding 3D volumes were generated and maximal dimensions
      along 3 directions (x, y, z), X M, Y M, Z M (in mm), total volume area (in
      mm(3)), V t, and total surface (in mm(2)), S t, were calculated. Correlation
      analysis showed that sinus surfaces were strongly correlated with their volume (r
      = 0.976). Frontal sinuses were separate in 21 subjects (14 %), fused in 67 (44.6
      %) and found on only one side (unilateral) in 9 (6 %). A Prominent Middle of
      Fused Sinus (PMS) was found in 53 subjects (35.3 %). The intra- (0.963-0.999) and
      inter-observer variability (0.973-0.999) showed a great agreement and a
      substantial homogeneity of evaluation. 

PMID- 25981383
TI  - Curcumin Reactivates Silenced Tumor Suppressor Gene RARbeta by Reducing DNA
      Methylation.
AB  - Reactivation of tumor suppressor genes by nontoxic bioactive food component
      represents a promising strategy for cancer chemoprevention. Retinoic acid
      receptor beta (RARbeta), one member of the RAR receptor family, is considered as
      a tumor suppressor. Reduced expression of RARbeta has been reported in lung
      cancer and other solid tumors. DNA hypermethylation of the promoter region of
      RARbeta is a major mechanism for its silencing in tumors. Recently, curcumin has
      been considered as a potential DNA methyltransferase inhibitor. Herein, we
      demonstrated that curcumin significantly elevate RARbeta expression at the mRNA
      and protein levels in tested cancer cells. Additionally, curcumin decreased
      RARbeta promoter methylation in lung cancer A549 and H460 cells. Mechanistic
      study demonstrated that curcumin was able to downregulate the mRNA levels of
      DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective
      effect against weight loss because of tumor burden. Tumor growth was strongly
      repressed by curcumin treatment. As the results from in vitro, RARbeta mRNA were
      increased and DNMT3b mRNA were decreased by curcumin treatment compared with the
      mice in control group. Altogether, this study reveals a novel molecular mechanism
      of curcumin as a chemo-preventive agent for lung cancer through reactivation of
      RARbeta.

PMID- 25981384
TI  - Nanoparticle Formulation of AEA and BAEA Cellulose Carbamates Increases
      Biocompatibility and Antimicrobial Activity.
AB  - Antimicrobially active polymers with a cationic moiety gain increasing interest
      in health care providing a biocompatible alternative to commonly used products.
      They adhere to the polyanionic bacterial surface, disrupt cell membranes and kill
      bacteria. An efficient path to obtain amino group-containing cellulose is
      nucleophilic displacement reaction of p-toluenesulfonic acid ester and amines
      leading to 6-deoxy-6-(omega-aminoalkyl) aminocellulose carbamates. Spherical
      nanoparticles of the obtained 6-deoxy-6-(2-aminoethyl) amino (AEA) and 6-deoxy-6
      {2-bis[N',N'-(2-aminoethyl)]aminoethyl}amino (BAEA) cellulose carbamate with a
      size range of 80-120 nm were produced. The AEA and BAEA cellulose carbamates
      exhibited significant antimicrobial activity with moderate cell compatibility.
      Nanoparticle formulation enhanced biocompatibility. 

PMID- 25981385
TI  - Another Beginning for Cystic Fibrosis Therapy.

PMID- 25981386
TI  - Mutual exclusion of Asaia and Wolbachia in the reproductive organs of mosquito
      vectors.
AB  - BACKGROUND: Wolbachia is a group of intracellular maternally inherited bacteria
      infecting a high number of arthropod species. Their presence in different
      mosquito species has been largely described, but Aedes aegypti, the main vector
      of Dengue virus, has never been found naturally infected by Wolbachia. Similarly,
      malaria vectors and other anophelines are normally negative to Wolbachia, with
      the exception of an African population where these bacteria have recently been
      detected. Asaia is an acetic acid bacterium stably associated with several
      mosquito species, found as a dominant microorganism of the mosquito microbiota.
      Asaia has been described in gut, salivary glands and in reproductive organs of
      adult mosquitoes in Ae. aegypti and in anophelines. It has recently been shown
      that Asaia may impede vertical transmission of Wolbachia in Anopheles mosquitoes.
      Here we present an experimental study, aimed at determining whether there is a
      negative interference between Asaia and Wolbachia, for the gonad niche in
      mosquitoes. METHODS: Different methods (PCR and qPCR, monoclonal antibody
      staining and FISH) have been used to address the question of the co-localization
      and the relative presence/abundance of the two symbionts. PCR and qPCR were
      performed to qualitatively and quantitatively verify the distribution of Asaia
      and Wolbachia in different mosquito species/organs. Monoclonal antibody staining
      and FISH were performed to localize the symbionts in different mosquito species.
      RESULTS: Here we provide evidence that, in Anopheles and in other mosquitoes,
      there is a reciprocal negative interference between Asaia and Wolbachia
      symbionts, in terms of the colonization of the gonads. In particular, we have
      shown that in some mosquito species the presence of one of the symbionts
      prevented the establishment of the second, while in other systems the symbionts
      were co-localized, although at reduced densities. CONCLUSIONS: A mutual exclusion
      or a competition between Asaia and Wolbachia may contribute to explain the
      inability of Wolbachia to colonize the female reproductive organs of anophelines,
      inhibiting its vertical transmission and explaining the absence of Wolbachia
      infection in Ae. aegypti and in the majority of natural populations of Anopheles
      mosquitoes.

PMID- 25981387
TI  - Crystal structures of tiotropium bromide and its monohydrate in view of combined
      solid-state nuclear magnetic resonance and gauge-including projector-augmented
      wave studies.
AB  - Tiotropium bromide is an anticholinergic bronchodilator used in the management of
      chronic obstructive pulmonary disease. The crystal structures of this compound
      and its monohydrate have been previously solved and published. However, in this
      paper, we showed that those structures contain some major errors. Our methodology
      based on combination of the solid-state nuclear magnetic resonance (NMR)
      spectroscopy and quantum mechanical gauge-including projector-augmented wave
      (GIPAW) calculations of NMR shielding constants enabled us to correct those
      errors and obtain reliable structures of the studied compounds. It has been
      proved that such approach can be used not only to perform the structural analysis
      of a drug substance and to identify its polymorphs, but also to verify and
      optimize already existing crystal structures.

PMID- 25981388
TI  - Prevention of stroke in rheumatoid arthritis.
AB  - OPINION STATEMENT: Recognizing that systemic inflammation is a major contributor
      to the increased risk of cardiovascular disease (CVD), including stroke, in
      rheumatoid arthritis (RA) serves as the basis for prevention strategies for
      cerebrovascular disease in RA. In addition to traditional cardiovascular risk
      factors, recognize that RA may be an independent risk factor for cerebrovascular
      accident (CVA). The risk of CVD should be assessed in each patient with RA,
      utilizing modified risk score calculators. Careful monitoring and control of
      systemic inflammation should be undertaken in conjunction with assessing each
      patient's CVD risk, acknowledging the benefits and risks of specific RA-directed
      therapies. Emphasis should be given to early and aggressive control of
      inflammation in RA patients, particularly those with seropositivity, increased
      inflammatory markers, long disease duration (>10 years), and/or extra-articular
      manifestations. In RA patients requiring glucocorticoid therapy, attempts should
      be made to use or wean to the minimal effective dose (preferably less than 7.5
      mg/day). It should be recognized that both disease-modifying antirheumatic drugs
      (DMARDs), particularly methotrexate, and tumor necrosis factor (TNF)-alpha
      inhibitors partially mitigate the risk of CVD. In patients with inadequate
      control of inflammation with DMARDs, consideration should be given to switch to
      anti-TNF agents earlier in the disease process. Modifiable risk factors should be
      addressed as per guidelines for the general population. Active RA may be
      considered as a risk equivalent to diabetes mellitus when applying these
      guidelines. With regard to lipid management and use of statin therapy, further
      studies are required given the apparent "lipid paradox" in RA. Use of aspirin for
      primary prevention in RA has not been well studied; however, when aspirin is used
      for secondary prevention, one should recognize that concomitant use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the antiplatelet
      effect. Given the cardiovascular risk associated with NSAIDs, the lowest possible
      dose for the shortest time should be used.

PMID- 25981389
TI  - Intra-arterial therapy for acute ischemic stroke: a golden age.
AB  - OPINION STATEMENT: With the recent publication of multiple trials demonstrating
      the superiority of the endovascular treatment of patients presenting with stroke
      from large vessel occlusion (LVO) over medical management, the emergent care of
      these patients is entering a new era. This realization justifies an aggressive
      treatment approach with these stroke patients, given the poor natural history of
      the disease. In general, treatment should occur as quickly as is reasonably
      possible. Patients with NIHSS >8 should be considered, and if <6 h from onset
      imaging selection achieved with CT and CTA. Those with ASPECTS >5, LVO and
      intermediate or good collaterals should be treated emergently. For patients with
      clinical deficits presenting in later timeframes MRI should be used to define
      core infarct size and therefore treatment eligibility. MRI might also be
      considered for the workup of stroke patients in centers that can offer it
      rapidly. Recanalization should be attempted with a stentriever or using a direct
      aspiration technique, with the patient under conscious sedation rather than
      general anesthesia, if that is a safe option. Angiographically, the goal is
      reperfusion of mTICI 2b/3. Post-procedure, the patient should be admitted to an
      intensive care setting and assessed for inpatient rehabilitation placement as
      soon as stable. Continuous institutional process improvement ensures that
      optimization of treatment times and logistics is an ongoing endeavor. Finally,
      patient outcomes should be assessed at three months, most commonly using the
      modified Rankin score.

PMID- 25981391
TI  - Synthesis of meso-substituted subphthalocyanine-subporphyrin hybrids: boron
      subtribenzodiazaporphyrins.
AB  - The first syntheses of hybrid structures that lie between subphthalocyanines and
      subporphyrins are reported. The versatile single-step synthetic method uses a
      preformed aminoisoindolene to provide the bridging methine unit and its
      substituent while trialkoxyborates simultaneously act as Lewis acid, template,
      and provider of the apical substituent. The selection of each component therefore
      allows for the controlled formation of diverse, differentially functionalized
      systems. The new hybrids are isolated as robust, pure materials that display
      intense absorption and emission in the mid-visible region. The new compounds are
      further characterized in solution and solid state by variable-temperature NMR
      spectroscopy and X-ray crystallography, respectively. 

PMID- 25981390
TI  - Shaping the future of nanomedicine: anisotropy in polymeric nanoparticle design.
AB  - Nanofabrication and biomedical applications of polymeric nanoparticles have
      become important areas of research. Biocompatible polymeric nanoparticles have
      been investigated for their use as delivery vehicles for therapeutic and
      diagnostic agents. Although polymeric nanoconstructs have traditionally been
      fabricated as isotropic spheres, anisotropic, nonspherical nanoparticles have
      gained interest in the biomaterials community owing to their unique interactions
      with biological systems. Polymeric nanoparticles with different forms of
      anisotropy have been manufactured using a variety of novel methods in recent
      years. In addition, they have enhanced physical, chemical, and biological
      properties compared with spherical nanoparticles, including increased targeting
      avidity and decreased nonspecific in vivo clearance. With these desirable
      properties, anisotropic nanoparticles have been successfully utilized in many
      biomedical settings and have performed superiorly to analogous spherical
      nanoparticles. We summarize the current state-of-the-art fabrication methods for
      anisotropic polymeric nanoparticles including top-down, bottom-up, and
      microfluidic design approaches. We also summarize the current and potential
      future applications of these nanoparticles, including drug delivery, biological
      targeting, immunoengineering, and tissue engineering. Ongoing research into the
      properties and utility of anisotropic polymeric nanoparticles will prove critical
      to realizing their potential in nanomedicine.

PMID- 25981393
TI  - Nano graphene oxide-wrapped gold nanostars as ultrasensitive and stable SERS
      nanoprobes.
AB  - We report a facile method to synthesize highly branched gold nanostars wrapped
      with nano graphene oxide (nGO) sheets with or without the addition of Raman dyes,
      as nanoprobes with high SERS activity. Both cysteamine and nGO are added to gold
      nanostars; the positively charged amino groups help self-assembly of nGO flakes
      around the nanostars. This increases the Raman signal of nGO by 5.3 folds
      compared to samples in which nGO is in contact with the nanostars but does not
      wrap them. We also prepare dye-based SERS nanoprobes by sandwiching a typical
      Raman reporter such as Rhodamine B (RhB), Crystal Violet (CV) and Rhodamine 6G
      (R6G) between the nanostars and the nGO coating. The Raman signals of RhB are 5.2
      times larger when sandwiched between nGO and nanostars than if the molecules are
      just adsorbed on the nanostar surface, and similar enhancements are observed for
      the other dyes. In addition to improving SERS efficiency, the wrapping greatly
      improves the stability of the dye-based nanoprobes, showing a reproducible Raman
      signal of RhB for over a week in simulated body fluids at 37  degrees C. High
      SERS signal, facile fabrication method and excellent stability make these
      nanoprobes highly promising for SERS-based biosensing and bioimaging
      applications. 

PMID- 25981392
TI  - MicroRNA expression profiles predict clinical phenotypes and prognosis in
      chromophobe renal cell carcinoma.
AB  - Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of
      kidney cancers. In the present study, we identified 58 treatment-naive primary
      chRCC patients from The Cancer Genome Atlas dataset and analyzed the genome-wide
      microRNA (miRNA) expression profiles, with the aim to assess the relationship of
      miRNA expression with the progression and prognosis of chRCC. Overall, a total of
      105 miRNAs were found to be differentially expressed between tumor and the
      adjacent normal tissues from 22 chRCC patients. In the unpaired condition (58
      chRCC vs. 22 normal tissues), 77 (96.3%) samples were distinguished correctly by
      the signatures. In the progression-related profiles, 27 miRNAs were selected for
      pathologic T and 9 for lymph node involvement. In the survival analyses, the
      expression levels of mir-191, mir-19a, mir-210, and mir-425 were significantly
      associated with both recurrence-free survival (RFS) and overall survival, while
      mir-210 was proven as an independent prognostic factor in terms of RFS. In
      summary, miRNAs are expressed differentially in chRCC, and unique expression of
      miRNAs is associated with the progression and prognosis of chRCC. 

PMID- 25981394
TI  - In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different
      Hemodialysis Treatments.
AB  - Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic
      hemolysis) is unavoidable during treatments that involve extracorporeal blood
      circulation, such as hemodialysis (HD). This effect is generally undetectable and
      does not generate any acute symptoms, but it leads to an increase in plasma free
      hemoglobin (fHb). There are no absolute safety levels for fHb increase,
      indicating the need for an empirical evaluation using comparative testing. The
      increase in fHb levels was investigated in vitro by applying double-needle double
      pump HD (HD-DNDP), a new modality in which arterial and venous pumps both run
      continuously. fHb was measured during typical and worst-case simulated dialysis
      treatments (double-needle single-pump HD [HD-DNSP], hemodiafiltration [HDF-DN],
      single-needle double-pump HD [HD-SNDP], and HD-DNDP) performed in vitro using
      bovine blood for 4 h. Hemolysis-related indices (fHb%; index of hemolysis, IH;
      and normalized IH) were calculated and used for comparison. The increase in fHb
      during either HDF-DN or HD-SNDP with Artis and AK200 dialysis machines was
      similar, while the fHb at the maximum real blood flow rate (Qbreal ) at the
      completion of the HD-DNDP treatment on Artis was higher than that for HD-DNSP
      using a Phoenix dialysis machine (fHb% = 1.24 +/- 0.13 and 0.92 +/- 0.12 for the
      Artis machine with HD-DNDP at Qbreal  = 450 mL/min and Phoenix with HD-DNSP at
      Qbreal  = 500 mL/min, respectively). However, the fHb levels increased linearly,
      and no steep changes were observed. The increases observed during HD-DNDP were
      the same order of magnitude as those for widely used bloodlines and treatment
      modes for delivering dialysis treatments. The observed results matched literature
      findings, and thus the measured fHb trends are not predicted to have clinical
      side effects. HD-DNDP treatment with Artis does not merit any additional concern
      regarding mechanical stress to RBCs compared with that observed for routinely
      used dialysis treatments, bloodlines and machines. Although the in vitro
      measurement of the fHb increase in bovine blood does not allow a prediction of
      the absolute level of blood mechanical damage or the possible effects in humans,
      such measurements are valuable for assessing hemolytic harm by performing tests
      comparing the proposed treatment with existing devices.

PMID- 25981395
TI  - Salvianolic acid B attenuates apoptosis and inflammation via SIRT1 activation in
      experimental stroke rats.
AB  - Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested
      to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a
      polyphenolic and one of the active components of Salvia miltiorrhiza Bunge.
      Previous studies suggested that SalB is protective against ischemic stroke.
      However, the role of SIRT1 in the protective effect of SalB against cerebral
      ischemia has not been explored. In this study, the rat brain was subjected to
      middle cerebral artery occlusion (MCAO). Before this surgery, rats were
      intraperitoneally administrated SalB with or without EX527, a specific SIRT1
      inhibitor. The infarct volume, neurological score and brain water content were
      assessed. In addition, levels of TNF-alpha and IL-1beta in the brain tissues were
      detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1,
      Bcl-2 and Bax were detected by Western blot. The results suggested that SalB
      exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered
      brain edema and increased neurological scores. SalB also exerted anti
      inflammatory effects as indicated by the decreased TNF-alpha and IL-1beta levels
      in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2
      and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were
      abolished by EX527 treatment. In summary, our results demonstrate that SalB
      treatment attenuates brain injury induced by ischemic stoke via reducing
      apoptosis and inflammation through the activation of SIRT1 signaling. 

PMID- 25981396
TI  - Recent advances in re-engineered liver: de-cellularization and re-cellularization
      techniques.
AB  - Allogeneic transplantation is the definitive treatment for patients with end
      stage liver disease but is limited by donor shortage and very high cost. Through
      de-cellularization and re-cellularization methods, re-engineered liver may
      provide a promising alternative for treating patients with end-stage liver
      disease. To achieve this, the prevention of the native extracellular matrix
      ultrastructure plays a central role in de-cellularization protocol; the re
      seeding cell types, as well as re-seeding strategies, need more explorations in
      re-cellularization protocol. Some success of this approach has been published in
      a rat model; however, the re-engineered liver remains functional in vivo for only
      several hours, which suggests that the recent protocol may be far from the ideal
      target. This Review highlights the challenges still to be overcome and presents
      an overview and summary of methods of de-cellularization and re-cellularization
      strategies, together with a view on future directions that may lead to the
      regeneration of a functional liver.

PMID- 25981397
TI  - Automated CD34+ cell isolation of peripheral blood stem cell apheresis product.
AB  - BACKGROUND AIMS: Immunomagnetic enrichment of CD34+ hematopoietic "stem" cells
      (HSCs) using paramagnetic nanobead coupled CD34 antibody and immunomagnetic
      extraction with the CliniMACS plus system is the standard approach to generating
      T-cell-depleted stem cell grafts. Their clinical beneficence in selected
      indications is established. Even though CD34+ selected grafts are typically given
      in the context of a severely immunosuppressive conditioning with anti-thymocyte
      globulin or similar, the degree of T-cell depletion appears to affect clinical
      outcomes and thus in addition to CD34 cell recovery, the degree of T-cell
      depletion critically describes process quality. An automatic immunomagnetic cell
      processing system, CliniMACS Prodigy, including a protocol for fully automatic
      CD34+ cell selection from apheresis products, was recently developed. We
      performed a formal process validation to support submission of the protocol for
      CE release, a prerequisite for clinical use of Prodigy CD34+ products. METHODS:
      Granulocyte-colony stimulating factor-mobilized healthy-donor apheresis products
      were subjected to CD34+ cell selection using Prodigy with clinical reagents and
      consumables and advanced beta versions of the CD34 selection software. Target and
      non-target cells were enumerated using sensitive flow cytometry platforms.
      RESULTS: Nine successful clinical-scale CD34+ cell selections were performed.
      Beyond setup, no operator intervention was required. Prodigy recovered 74 +/- 13%
      of target cells with a viability of 99.9 +/- 0.05%. Per 5 * 10E6 CD34+ cells,
      which we consider a per-kilogram dose of HSCs, products contained 17 +/- 3 * 10E3
      T cells and 78 +/- 22 * 10E3 B cells. CONCLUSIONS: The process for CD34 selection
      with Prodigy is robust and labor-saving but not time-saving. Compared with
      clinical CD34+ selected products concurrently generated with the predecessor
      technology, product properties, importantly including CD34+ cell recovery and T
      cell contents, were not significantly different. The automatic system is suitable
      for routine clinical application.

PMID- 25981398
TI  - Assessment of Peripheral Neuropathy Using Measurement of the Current Perception
      Threshold with the Neurometer(r) in patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: The aim of this study is to evaluate the role of current perception
      threshold (CPT) measurement in peripheral neuropathy in type 1 diabetic patients
      by using the Neurometer((r)), a nerve measuring instrument. METHODS: 52 patients
      with type 1 diabetes mellitus with a disease duration of less than five years and
      normal neuropathy symptom score (NSS), neuropathy disability score (NDS) and
      sensory nerve conduction velocity (SCV), and 40 healthy controls were enrolled in
      this study. Measurement of CPT using the Neurometer((r)) at 2000, 250 and 5 Hz
      assesses function in the bilateral median nerve and sural nerve in all studied
      cases. We also evaluated the glycated hemoglobin, microalbuminuria, urinary
      albumin/creatinine ratio and other metabolism indexes of all patients. RESULTS:
      The CPT of the bilateral median nerve and sural nerve was significantly lower in
      diabetic patients (P<0.01). Moreover, the number of median nerve injuries in the
      diabetic group (left side 8/52, right side 8/52) is significantly different from
      the number of its ipsilateral sural nerve injuries (left side 28/52, right side
      22/52) (left side P<0.01, right side P<0.01). By comparing those with DPN and
      those without DPN in the diabetic group, DPN groups had significantly higher
      glycated hemoglobin (t=2.518, P<0.05). Using binary logistic regression, high
      glycated hemoglobin was identified to be an independent risk factor of DPN
      incidence (OR (95% CI): 1.317 (1.013 -1.712), P<0.05). CONCLUSION: These data
      suggest that CPT is useful in early detection of peripheral neuropathy in
      patients with type 1 diabetes mellitus. Patients with diabetic peripheral
      neuropathy, the lower limb nerve is more vulnerable than the upper limb nerve. In
      addition, patients with DPN had higher glycated hemoglobin which is an
      independent risk factor of DPN.

PMID- 25981399
TI  - Changes in receptivity epithelial cell markers of endometrium after ovarian
      stimulation treatments: its role during implantation window.
AB  - BACKGROUND: To compare the expression of receptivity markers in epithelial and
      stromal cells in the endometrium of ovulatory women and infertile with
      hypothalamic pituitary dysfunction (HPD), untreated or treated with clomiphene
      citrate (CC), or with recombinant follicle stimulating hormone (rFSH). METHODS:
      Twelve control ovulatory and 32 anovulatory women, 22 of whom received ovulation
      induction with CC (n = 12) or rFSH (n = 10). Endometrial biopsies were obtained
      during the mid-secretory phase. Hormonal secretion was measured by
      chemiluminescence immunoassay, endometrial dating and cellular expression and
      distribution of receptivity proteins were evaluated by quantitative
      immunohistochemistry. RESULTS: CC or rFSH treatments, modified the expression of
      epithelial receptivity markers, such as Glycodelin A, beta-catenin, CD166/ALCAM
      and IGF-1R, but not in stromal markers. Also, a change in their cell distribution
      was observed. CONCLUSIONS: Treatment of infertile women with HPD modified the
      expression and distribution of receptivity markers in the mid-secretory phase of
      the endometrium in epithelial but not stromal cells, which can help to explain
      changes in the receptivity of the endometrium during treatments and suggest an
      important role of these cells in the receptivity window.

PMID- 25981400
TI  - Involvement of renin-angiotensin-aldosterone system in calcium oxalate crystal
      induced activation of NADPH oxidase and renal cell injury.
AB  - INTRODUCTION AND OBJECTIVES: Reactive oxygen species (ROS) are produced during
      the interaction between oxalate/calcium oxalate monohydrate (COM) crystals and
      renal epithelial cells and are responsible for the various cellular responses
      through the activation of NADPH oxidase (Nox). Ox and COM also activate the renin
      angiotensin-aldosterone system (RAAS). Aldosterone stimulates ROS production
      through activation of Nox with the involvement of mineralocorticoid receptor
      (MR), Rac1 and mitogen-activated protein kinases (MAPK). We investigated RAAS
      pathways in vivo in an animal model of hyperoxaluria and in vitro by exposing
      renal epithelial cells to COM crystals. METHODS: Hyperoxaluria was induced in
      male SD rats by administering ethylene glycol. One group of rats was additionally
      given spironolactone. Total RNA was extracted and subjected to genomic
      microarrays to obtain global transcriptome data. Normal rat kidney cell line (NRK
      52E) was incubated with aldosterone(10(-7) M) and COM(67 MUg/cm(2)) with or
      without spironolactone(10(-5) M), a selective inhibitor of SRC family of kinases;
      protein phosphatase 2(pp2) (10(-5) M) and Nox inhibitor; diphenylene iodonium
      (DPI) (10(-5) M). RESULTS: Relative expression of genes encoding for AGT,
      angiotensin receptors 1b and 2, Renin 1, Cyp11b, HSD11B2, Nr3c2, NOx4 and Rac1
      was upregulated in the kidneys of rats with hyperoxaluria. Treatment with
      spironolactone reversed the effect of hyperoxaluria. Both aldosterone and COM
      crystals activated Nox and Rac1 expression in NRK52E, while spironolactone
      inhibited Nox and Rac1 expression. Increased Rac1 expression was significantly
      attenuated by treatment with PP2 and spironolactone. CONCLUSIONS: Results
      indicate that hyperoxaluria-induced production of ROS, injury and inflammation
      are in part associated with the activation of Nox through renin-angiotensin
      aldosterone pathway.

PMID- 25981402
TI  - Prognostic factors and outcomes in primary urethral cancer: results from the
      international collaboration on primary urethral carcinoma.
AB  - PURPOSE: To evaluate risk factors for survival in a large international cohort of
      patients with primary urethral cancer (PUC). METHODS: A series of 154 patients
      (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993
      and 2012. Kaplan-Meier analysis with log-rank test was used to investigate
      various potential prognostic factors for recurrence-free (RFS) and overall
      survival (OS). Multivariate models were constructed to evaluate independent risk
      factors for recurrence and death. RESULTS: Median age at definitive treatment was
      66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous
      cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other
      histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance
      between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001)
      was noted. For clinical nodal staging, the corresponding sensitivity,
      specificity, and overall accuracy for predicting pathologic nodal stage were
      92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis
      for patients staged cM0 at initial diagnosis, RFS was significantly associated
      with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p =
      0.001), whereas clinical nodal stage was the only independent predictor for OS (p
      = 0.026). CONCLUSIONS: These data suggest that clinical nodal stage is a critical
      parameter for outcomes in PUC.

PMID- 25981401
TI  - Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron
      sparing surgery: quantitative assessment by NGAL and KIM-1.
AB  - PURPOSE: Interruption of renal blood flow is often necessary during nephron
      sparing surgery (NSS) and can induce renal injury. This study examines whether
      tadalafil, a phosphodiesterase-5 (PDE-5) inhibitor and well-known vasodilator,
      exerts nephroprotective effects in patients undergoing NSS. METHODS: This non
      randomized study included 49 patients with enhancing solid renal mass. All
      patients were subjected to open NSS during which clamping the renal artery was
      performed. Twenty-two patients were pretreated with tadalafil 1 day prior NSS and
      2 days following surgery. The other 27 patients underwent the same surgical
      procedure but did not receive tadalafil (controls). Urine samples were collected
      before surgery and following renal pedicle clamp removal. Urine levels of NGAL
      and KIM-1, two novel biomarkers for acute kidney injury (AKI), were determined.
      RESULTS: Clamping the renal artery induced kidney dysfunction as reflected by
      increases in urinary NGAL and KIM-1 in all participants. These increases in
      urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted
      for 72 and 24 h, respectively. Pretreatment with tadalafil reduced the absolute
      urinary excretion of KIM-1, but not of NGAL. Although the incidence of AKI was
      comparable between tadalafil-treated and untreated NSS subjects, the elevation in
      serum creatinine (SCr) was significantly attenuated in tadalafil-treated group as
      compared with NSS controls. CONCLUSIONS: Tadalafil exerts nephroprotective
      effects in AKI following NSS, as was evident by reduced urinary excretion of KIM
      1 and attenuation of SCr elevation. Carefully controlled large clinical studies
      are needed before defining the role of PDE-5 inhibition therapy in these
      patients.

PMID- 25981403
TI  - Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive
      regions of interest.
AB  - PURPOSE: Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to
      systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric
      magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas
      of the prostate instead of random 12-core biopsy. This method has been shown to
      be more accurate in detecting significant PCa. However, the precise spatial
      accuracy of cognitive targeting is unknown. METHODS: Consecutive patients
      undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed
      by robot-assisted radical prostatectomy were included in the present analysis.
      The regions of interest (ROIs) involved by the index lesion reported on mpMRI
      were subsequently targeted by two experienced urologists using the cognitive
      approach. The 27 ROIs were used as spatial reference. Mapping on radical
      prostatectomy specimen was used as reference to determine true-positive mpMRI
      findings. Per core correlation analysis was performed. RESULTS: Forty patients
      were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index
      lesion 3.43) were identified on MRI. After correlating these findings with final
      pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of
      102 biopsy cores directed toward such true-positive ROIs were available for final
      analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102).
      The only identified risk factor for missing the target was an anterior situated
      ROI (p = 0.01). CONCLUSION: In experienced hands, cognitive MRTB-COG allows for
      an accuracy of 82 % in hitting the correct target, given that it is a true
      positive lesion. Anterior tumors are less likely to be successfully targeted.

PMID- 25981404
TI  - The impact of three-dimensional tumor volume on cancer-specific survival for
      patients with pT1 clear-cell renal cell carcinoma.
AB  - PURPOSE: To evaluate the impact of three-dimensional tumor volume on cancer
      specific survival for patients with pT1 clear-cell renal cell carcinoma (ccRCC).
      MATERIALS AND METHODS: We reviewed a prospectively maintained database of 917
      patients who underwent radical nephrectomy or nephron-sparing surgery for
      unilateral, pT1 ccRCC, including 654 pT1a and 263 pT1b patients, between April
      1997 and December 2010. Three-dimensional tumor volume was measured using
      specialized volumetric software on cross-sectional computed tomography images of
      a preoperative venous phase. Kaplan-Meier and Cox regression analyses were
      carried out. RESULTS: The median age was 54 years with a follow-up of 60.8
      months. Median tumor size and volume were 3.2 cm and 17.4 cm(3), respectively. Of
      917 patients, 54 (5.9 %) had died, including 32 patients with ccRCC (9 patients
      in pT1a and 23 patients in pT1b). On multivariate analysis, tumor size >3.2 cm
      and tumor volume >17.4 cm(3) were associated with cancer-specific death in pT1
      ccRCC patients. When stratified by pT1a/pT1b status and analyzed on median
      splits, tumor size >2.5 cm was associated with cancer-specific death but not
      tumor volume >9.5 cm(3) in pT1a patients. However, in pT1b patients, tumor volume
      >62.1 cm(3) (P = 0.036, HR 2.91, 95 % CI 1.02-7.77) was highly associated with
      cancer-specific death but not tumor size >5.0 cm (P = 0.159, HR 1.91, 95 % CI
      0.78-4.70). CONCLUSIONS: In addition to tumor size, tumor volume is associated
      with cancer-specific death in pT1 ccRCC patients, particularly in pT1b ccRCC but
      not in pT1a ccRCC.

PMID- 25981405
TI  - A flexible, stretchable and shape-adaptive approach for versatile energy
      conversion and self-powered biomedical monitoring.
AB  - A flexible triboelectric nanogenerator (FTENG) based on wavy-structured Kapton
      film and a serpentine electrode on stretchable substrates is presented. The as
      fabricated FTENG is capable of harvesting ambient mechanical energy via both
      compressive and stretching modes. Moreover, the FTENG can be a bendable power
      source to work on curved surfaces; it can also be adaptively attached onto human
      skin for monitoring gentle body motions. 

PMID- 25981406
TI  - Management Strategies Aiming to Improve Horse Welfare Reduce Embryonic Death
      Rates in Mares.
AB  - The objective of this retrospective study was to evaluate the effect of
      management strategies aiming to improve animal well-being on pregnancy and
      embryonic death (ED) rates. Breeding records of a cohort of 1206 Thoroughbred
      mares brought to a stallion station facility, to be bred with the stallions
      housed there, were evaluated during ten breeding seasons. Mares were blocked
      according to management strategies in two groups: Stress and Relax. Strategies
      used to improve animal well-being (Relax group) were as follows: stopping the
      teasing routine, reducing or eliminating stall confinement, reducing the number
      of mares per group and maintaining herd stability during the breeding season. In
      barren mares, the pregnancy rate was higher in the Relax group (91.8%) when
      compared to the observed in Stress group (84.7%). However, no difference in
      pregnancy rates were observed (Stress = 85.2% vs. Relax = 86.2) in foaling mares.
      ED rate was higher in barren and foaling mares of the Stress group mares (25.5%
      and 26.8%, respectively) compared with the Relax group (16.1% and 14.7%,
      respectively). No significant differences were observed on foal heat pregnancy
      rate between groups; yet, the embryo loss on foal heat was significant reduced in
      Relax mares (Relax = 8.7% vs Stress = 24.5%). In conclusion, management
      strategies aimed to reduce social stress can reduce early pregnancy losses and
      the average cycles per pregnancy, improving reproductive performance in mares. 

PMID- 25981407
TI  - Determination of the Mercury Fraction Linked to Protein of Muscle and Liver
      Tissue of Tucunare (Cichla spp.) from the Amazon Region of Brazil.
AB  - This study used metalloproteomic techniques to characterize mercury (Hg)-bound
      proteins in the muscle and liver tissue of Tucunare (Cichla spp.) collected at
      the Jirau Hydroelectric Power Plant in Madeira River Basin, Brazil. The proteome
      of the muscle and liver tissue was obtained after two steps of fractional
      precipitation and separating the proteins by 2-D polyacrylamide gel
      electrophoresis. Hg was identified and quantified in the protein spots by
      graphite furnace atomic absorption spectrometry after acid mineralization in an
      ultrasound bath. Hg with a molecular weight <20 kDa and a concentration between
      13.30 and 33.40 mg g(-1) was found in the protein spots. These protein spots were
      characterized by electrospray ionization tandem mass spectrometry after trypsin
      digestion. From a total of 12 analyzed spots, seven proteins showing Hg biomarker
      characteristics were identified: parvalbumin and its isoforms, ubiquitin-40S
      ribosomal protein S27a, zinc (Zn) finger and BTB domain-containing protein 24,
      and dual-specificity protein phosphatase 22-B. 

PMID- 25981408
TI  - A Metalloproteomics Study on the Association of Mercury With Breast Milk in
      Samples From Lactating Women in the Amazon Region of Brazil.
AB  - This study aimed to identify metalloproteins that lose their metal ions in the
      presence of mercury (Hg) and bind to Hg in breast milk samples collected from the
      riverine population of the Madeira River, a tributary of the Amazon River.
      Initially, total Hg was determined from the hair of lactating women to identify
      individuals who were contaminated followed by a proteomic analysis of breast milk
      samples through two-dimensional polyacrylamide gel electrophoresis after acetone
      precipitation. The presence of Hg in the obtained protein spots was determined by
      cold vapor atomic absorption spectrometry and cold vapor atomic fluorescence
      spectrometry. These determinations indicated the presence of Hg in one protein
      spot, which was then characterized through electrospray ionization tandem mass
      spectrometry. Based on searches in the UniProt database, this protein spot was
      identified as lysozyme C. 

PMID- 25981410
TI  - Introduction: Invertebrate Neuropeptides XV.

PMID- 25981409
TI  - Functional MRI of the Brainstem: Common Problems and their Solutions.
AB  - Functional magnetic resonance imaging (fMRI) of the brainstem is a relatively
      young field that is rapidly evolving. While it is still difficult to obtain
      usable fMRI signals from this complicated brain region, the past few years have
      seen a number of important advances that bring us closer to routine application
      of this method in the clinical and scientific setting. This review gives an
      overview of the technical capabilities and limitations of brainstem fMRI. It
      explains the major brainstem-specific problems and gives advice on how to avoid
      or counteract them. In particular, I discuss how spatial resolution issues can be
      overcome by using appropriate sequences, coils, and spatial preprocessing, how
      the effects of physiological noise can be mitigated by noise modeling and spatial
      masking, and how the functional heterogeneity of brainstem nuclei needs to be
      taken into account, when planning a study. Solving these common problems is a
      prerequisite for any scientist or clinician interested in applying fMRI to
      measure brainstem activity. 

PMID- 25981411
TI  - Inferring the effects of potential dispersal routes on the metacommunity
      structure of stream insects: as the crow flies, as the fish swims or as the fox
      runs?
AB  - 1. Metacommunity research relies largely on proxies for inferring the effect of
      dispersal on local community structure. Overland and watercourse distances have
      been typically used as such proxies. A good proxy for dispersal should, however,
      take into account more complex landscape features that can affect an organism's
      movement and dispersal. The cost distance approach does just that, allowing
      determining the path of least resistance across a landscape. 2. Here, we examined
      the distance decay of assemblage similarity within a subarctic stream insect
      metacommunity. We tested whether overland, watercourse and cumulative cost
      distances performed differently as correlates of dissimilarity in assemblage
      composition between sites. We also investigated the effect of body size and
      dispersal mode on metacommunity organization. 3. We found that dissimilarities in
      assemblage composition correlated more strongly with environmental than physical
      distances between sites. Overland and watercourse distances showed similar
      correlations to assemblage dissimilarity between sites, being sometimes
      significantly correlated with biological variation of entire insect communities.
      In metacommunities deconstructed by body size or dispersal mode, contrary to our
      expectation, passive dispersers showed a slightly stronger correlation than
      active dispersers to environmental differences between sites, although passive
      dispersers also showed a stronger correlation than active dispersers to physical
      distances between sites. The strength of correlation between environmental
      distance and biological dissimilarity also varied slightly among the body size
      classes. 4. After controlling for environmental differences between sites,
      cumulative cost distances were slightly better correlates of biological
      dissimilarities than overland or watercourse distances between sites. However,
      quantitative differences in correlation coefficients were small between different
      physical distances. 5. Although environmental differences typically override
      physical distances as determinants of the composition of stream insect
      assemblages, correlations between environmental distances and biological
      dissimilarities are typically rather weak. This undetermined variation may be
      attributable to dispersal processes, which may be captured using better proxies
      for the process. We suggest that further modifying the measurement of cost
      distances may be a fruitful avenue, especially if complemented by more direct
      natural history information on insect dispersal behaviour and distances travelled
      by them.

PMID- 25981412
TI  - A Physicochemical and Pharmacological Study of the Newly Synthesized Complex of
      Albendazole and the Polysaccharide Arabinogalactan from Larch Wood.
AB  - Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan
      from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid
      state mechanochemical technology. We investigated physicochemical properties of
      the synthesized complexes in the solid state and in aqueous solutions as well as
      their anthelmintic activity against Trichinella spiralis, Hymenolepis nana,
      Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep.
      Formation of the complexes was demonstrated by means of intrinsic solubility and
      the NMR relaxation method. The mechanochemically synthesized complexes were more
      stable in comparison with the complex produced by mixing solutions of the
      components. The complexes of ABZ showed anthelmintic activity at 10-fold lower
      doses than did free ABZ. The complexes also showed lower acute toxicity and
      hepatotoxicity. These results suggest that it is possible to design new drugs on
      the basis of the ABZ:arabinogalactan complex that are safer and more effective
      than albendazole. 

PMID- 25981415
TI  - Surface morphology of Au-free grown nanowires after native oxide removal.
AB  - Using scanning tunneling microscopy, we evaluate the surface structure and
      morphology down to the atomic scale for micrometers along Au-free grown InAs
      nanowires (NWs) free from native oxide. We find that removal of the native oxide
      (which covers the NWs upon exposure to the ambient air) using atomic hydrogen
      does not alter the underlying step structure. Imaging with sub-nanometer
      resolution along the NWs, we find an extremely low tapering (diameter change
      along the NW) of 1.7 +/- 0.5 AMUm(-1). A surface morphology with monolayer high
      islands, whose shape was influenced by stacking faults, was found to cover the
      NWs and was attributed to the decomposed native oxide. The appearance of point
      defects in the form of As-vacancies at the surface is analyzed and we set limits
      to the amount of carbon impurities in the NWs. 

PMID- 25981413
TI  - Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular
      Dystrophy.
AB  - Preservation of cell identity is necessary for homeostasis of most adult tissues.
      This process is challenged every time a tissue undergoes regeneration after
      stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal
      muscle regenerative capacity declines gradually as fibrosis increases. Using
      genetically engineered tracing mice, we demonstrate that, in dystrophic muscle,
      specialized cells of muscular, endothelial, and hematopoietic origins gain
      plasticity toward a fibrogenic fate via a TGFbeta-mediated pathway. This results
      in loss of cellular identity and normal function, with deleterious consequences
      for regeneration. Furthermore, this fibrogenic process involves acquisition of a
      mesenchymal progenitor multipotent status, illustrating a link between
      fibrogenesis and gain of progenitor cell functions. As this plasticity also was
      observed in DMD patients, we propose that mesenchymal transitions impair
      regeneration and worsen diseases with a fibrotic component. 

PMID- 25981414
TI  - A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of
      Stem Cell Progeny following Transplantation.
AB  - The utility of stem cells and their progeny in adult transplantation models has
      been limited by poor survival and integration. We designed an injectable and
      bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested
      it with two cell types in two animal models, thereby gaining an understanding of
      its general applicability for enhanced cell distribution, survival, integration,
      and functional repair relative to conventional cell delivery in saline. HAMC
      improves cell survival and integration of retinal stem cell (RSC)-derived rods in
      the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of
      the CD44 receptor with HA. Transient disruption of the retinal outer limiting
      membrane, combined with HAMC delivery, results in significantly improved rod
      survival and visual function. HAMC also improves the distribution, viability, and
      functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery
      system improves cell transplantation efficacy in two CNS models, suggesting broad
      applicability. 

PMID- 25981416
TI  - Health information technology data standards get down to business: maturation
      within domains and the emergence of interoperability.

PMID- 25981417
TI  - Power-sharing Partnerships: Teachers' Experiences of Participatory Methodology.
AB  - BACKGROUND: This article reports on the experiences of teachers as coresearchers
      in a long-term partnership with university researchers, who participated in an
      asset-based intervention project known as Supportive Teachers, Assets and
      Resilience (STAR). In an attempt to inform participatory research methodology,
      the study investigated how coresearchers (teachers) experienced power relations.
      We utilized Gaventa's power cube as a theoretical framework and participatory
      research as our methodologic paradigm. METHOD: Ten teachers of a primary school
      in the Eastern Cape and five teachers of a secondary school in a remote area in
      the Mpumalanga Province in South Africa participated (n=15). We employed multiple
      data generation techniques, namely Participatory Reflection and Action (PRA)
      activities, observation, focus group discussions, and semistructured interviews,
      using thematic analysis and categorical aggregation for data analysis. RESULTS:
      We identified three themes, related to the (1) nature of power in participatory
      partnerships, (2) coreasearchers' meaning making of power and partnerships, and
      their (3) role in taking agency. CONCLUSION: Based on these findings, we
      developed a framework of power sharing partnerships to extend Gaventa's power
      cube theory. This framework, and its five interrelated elements (leadership as
      power, identifying vision and mission, synergy, interdependent role of partners,
      and determination), provide insight into the way coresearchers shared their
      experiences of participatory research methodology. We theorise power-sharing
      partnerships as a complimentary platform hosting partners' shared strengths,
      skills, and experience, creating synergy in collaborative projects.

PMID- 25981422
TI  - PhotoVoice: A Community-Based Participatory Approach in Developing Disaster
      Reduction Strategies.
AB  - INTRODUCTION: The traditional centralized approach to disaster preparedness fails
      to take into consideration the unique geographic, historic, cultural, and social
      needs of communities. It often puts vulnerable communities more at risk by
      directing them to follow a one-size-fits-all model. Community-based participatory
      research (CBPR) approaches can increase awareness and customize the disaster
      reduction strategies to meet a community's unique needs. OBJECTIVE: To partner
      with a vulnerable community in Hawaii in conducting a hazard-specific
      vulnerability and capability assessment utilizing PhotoVoice and the core
      principles of CBPR. METHODS: A community participated in a PhotoVoice project to
      identify and categorize their vulnerabilities and capabilities, identify gaps,
      and develop solutions or strategies to reduce their vulnerability to a tsunami.
      RESULTS: Forty-two vulnerabilities and 50 capabilities within the community were
      identified and then categorized through photo presentations and discussion
      sessions. These were sorted into 17 themes, including communications,
      accessibility, historic and cultural, emergency notification, food, and water.
      Based on the vulnerability and capability assessment, 13 gaps were then
      identified and discussed, yielding 16 feasible strategies to reduce the
      community's vulnerability. CONCLUSIONS: PhotoVoice was found to be a successful
      community-based participatory process to assist a vulnerable community to develop
      contextually appropriate disaster reduction strategies through visual dialogue,
      which increased community awareness, engagement, and capacity.

PMID- 25981421
TI  - Research for improved health: variability and impact of structural
      characteristics in federally funded community engaged research.
AB  - BACKGROUND: Although there is strong scientific, policy, and community support
      for community-engaged research (CEnR)-including community-based participatory
      research (CBPR)-the science of CEnR is still developing. OBJECTIVE: To describe
      structural differences in federally funded CEnR projects by type of research
      (i.e., descriptive, intervention, or dissemination/policy change) and
      race/ethnicity of the population served. METHODS: We identified 333 federally
      funded projects in 2009 that potentially involved CEnR, 294 principal
      investigators/project directors (PI/PD) were eligible to participate in a key
      informant (KI) survey from late 2011 to early 2012 that asked about partnership
      structure (68% response rate). RESULTS: The National Institute on Minority Health
      & Health Disparities (19.1%), National Cancer Institute (NCI; 13.3%), and the
      Centers for Disease Control and Prevention (CDC; 12.6%) funded the most CEnR
      projects. Most were intervention projects (66.0%). Projects serving American
      Indian or Alaskan Native (AIAN) populations (compared with other community of
      color or multiple-race/unspecified) were likely to be descriptive projects
      (p<.01), receive less funding (p<.05), and have higher rates of written
      partnership agreements (p<.05), research integrity training (p<.05), approval of
      publications (p<.01), and data ownership (p<.01). AIAN-serving projects also
      reported similar rates of research productivity and greater levels of resource
      sharing compared with those serving multiple-race/unspecified groups.
      CONCLUSIONS: There is clear variability in the structure of CEnR projects with
      future research needed to determine the impact of this variability on partnering
      processes and outcomes. In addition, projects in AIAN communities receive lower
      levels of funding yet still have comparable research productivity to those
      projects in other racial/ethnic communities.

PMID- 25981423
TI  - Across the Miles: Process and Impacts of Collaboration with a Rural Community
      Advisory Board in HIV Research.
AB  - BACKGROUND: Project Education and Access to Services and Testing (EAST) worked
      with a community advisory board (CAB) to (1) identify individual-level, provider
      level, and community-level factors influencing attitudes about human
      immunodeficiency virus (HIV) and HIV/acquired immuno-deficiency syndrome (AIDS)
      research and (2) develop and test a community-based HIV clinical trials
      educational intervention in six rural counties in the Southeast. OBJECTIVES: We
      describe the processes and impact of forming and collaborating with a rural,
      multicommunity CAB. METHODS: CAB members included community leaders, providers,
      and people living with HIV/AIDS (PLWHA). CAB engagement emphasized respect and
      confidentiality. Tape-recorded meeting minutes and debriefing notes were used in
      analysis. RESULTS: The CAB identified physical and social parameters of the
      communities, built community trust, informed research design and implementation,
      and helped to navigate the impact of stigma. Major barriers to engagement were
      distance and geographic dispersion. CONCLUSIONS: CABs can make a critical
      difference in conducting culturally appropriate and successful research in rural
      communities.

PMID- 25981424
TI  - Taking a community-based participatory research approach in the development of
      methods to measure a community health worker community advocacy intervention.
AB  - BACKGROUND: Public health advocacy is by necessity responsive to shifting
      sociopolitical climates, and thus a challenge of advocacy research is that the
      intervention must by definition be adaptive. Moving beyond the classification of
      advocacy efforts to measurable indicators and outcomes of policy, therefore,
      requires a dynamic research approach. OBJECTIVES: The purposes of this article
      are to (1) describe use of the CBPR approach in the development and measurement
      of a community health worker (CHW) intervention designed to engage community
      members in public health advocacy and (2) provide a model for application of this
      approach in advocacy interventions addressing community-level systems and
      environmental change. METHODS: The Kingdon three streams model of policy change
      provided a theoretical framework for the intervention. Research and community
      partners collaboratively identified and documented intervention data. We describe
      five research methods used to monitor and measure CHW advocacy activities that
      both emerged from and influenced intervention activities. DISCUSSION: Encounter
      forms provided a longitudinal perspective of how CHWs engaged in advocacy
      activities in the three streams. Strategy maps defined desired advocacy outcomes
      and health benefits. Technical assistance notes identified and documented
      intermediate outcomes. Focus group and interview data reflected CHW efforts to
      engage community members in advocacy and the development of community leaders.
      APPLICATION OF LESSONS LEARNED: We provide a model for application of key
      principles of CPBR that are vital to effectively capturing the overarching and
      nuanced aspects of public health advocacy work in dynamic political and
      organizational environments.

PMID- 25981425
TI  - Undoing Racism Through Genesee County's REACH Infant Mortality Reduction
      Initiative.
AB  - BACKGROUND: Genesee County Racial and Ethnic Approaches to Community Health
      Program (REACH) is a Community-Based Public Health partnership for reducing
      African American infant mortality rates that hosts the Undoing Racism Workshop
      (URW). OBJECTIVES: Assess the URW's effectiveness in promoting an understanding
      of racism, institutional racism, and how issues related to race/ethnicity can
      affect maternal and infant health. METHODS: Recent URW participants (n=84)
      completed brief preassessment and postassessment forms; participants (n=101) also
      completed an on-line, long-term assessment (LTA). RESULTS: URWs promoted
      understanding of racism and institutional racism, although they were less
      effective in addressing racism as related to maternal and infant health.
      CONCLUSIONS: The URWs were most effective in the domains related to their
      standard content. Additional effort is necessary to customize URWs when utilized
      for activities beyond their original purpose of community mobilization.

PMID- 25981426
TI  - Using CBPR for Health Research in American Muslim Mosque Communities.
AB  - BACKGROUND: American Muslims are understudied in health research, and there are
      few studies documenting community-based participatory research (CBPR) efforts
      among American Muslim mosque communities. OBJECTIVES: We highlight lessons
      learned from a CBPR partnership that explored the health care beliefs, behaviors,
      and challenges of American Muslims. METHODS: We established a collaboration
      between the University of Michigan and four Muslim-focused community
      organizations in Michigan. Our collaborative team designed and implemented a two
      phase study involving interviews with community stakeholders and focus groups and
      surveys with mosque congregants. LESSONS LEARNED: Although we were successful in
      meeting our research goals, maintaining community partner involvement and
      sustaining the project partnership proved challenging. CONCLUSIONS: CBPR
      initiatives within mosque communities have the potential for improving community
      health. Our experience suggests that successful research partnerships with
      American Muslims will utilize social networks and cultural insiders, culturally
      adapt research methods, and develop a research platform within the organizational
      infrastructures of the American Muslim community.

PMID- 25981428
TI  - Somali Perspectives on Physical Activity: PhotoVoice to Address Barriers and
      Resources in San Diego.
AB  - BACKGROUND: Although many immigrants enter the United States with a healthy body
      weight, this health advantage disappears the longer they reside in the United
      States. To better understand the complexities of obesity change within a cultural
      framework, a community-based participatory research (CBPR) approach, PhotoVoice,
      was used, focusing on physical activity among Muslim Somali women. OBJECTIVES:
      The CBPR partnership was formed to identify barriers and resources to engaging in
      physical activity with goals of advocacy and program development. METHODS: Muslim
      Somali women (n=8) were recruited to participate, trained and provided cameras,
      and engaged in group discussions about the scenes they photographed. RESULTS:
      Participants identified several barriers, including safety concerns, minimal
      culturally appropriate resources, and financial constraints. Strengths included
      public resources and a community support system. The CBPR process identified
      opportunities and challenges to collaboration and dissemination processes.
      CONCLUSIONS: The findings laid the framework for subsequent program development
      and community engagement.

PMID- 25981429
TI  - Peer Mentoring for Male Parolees: A CBPR Pilot Study.
AB  - BACKGROUND: Formerly incarcerated adults are impoverished, have high rates of
      substance use disorders, and have long histories of imprisonment. This article
      describes the development of a peer mentoring program for formerly incarcerated
      adults and the pilot study designed to evaluate it. The research team, which
      included formerly incarcerated adults and academic researchers, developed the
      peer mentoring program to support formerly incarcerated adults' transition to the
      community after prison. OBJECTIVES: The purposes of the pilot evaluation study
      were to (1) assess the feasibility of implementing a peer-based intervention for
      recently released men developed using a community-based participatory research
      (CBPR) approach; (2) establish preliminary data on the program's impact on
      coping, self-esteem, abstinence self-efficacy, social support, and participation
      in 12-step meetings; and (3) establish a CBPR team of formerly incarcerated
      adults and academic researchers to develop, implement, and test interventions for
      this population. METHOD: This pilot evaluation study employed a mixed-methods
      approach with a single group pretest/posttest design with 20 men on parole
      released from prison within the last 30 days. RESULTS: Quantitative findings
      showed significant improvement on two abstinence self-efficacy subscales,
      negative affect and habitual craving. Qualitative findings revealed the relevance
      and acceptance of peer mentoring for this population. CONCLUSIONS: This study
      demonstrated the feasibility and import of involving formerly incarcerated adults
      in the design, implementation, and testing of interventions intended to support
      their reintegration efforts.

PMID- 25981430
TI  - Building community while complying with the Affordable Care Act in the Lehigh
      Valley of Pennsylvania.
AB  - PROBLEM: The Affordable Care Act (ACA) requires nonprofit hospitals to conduct
      community health needs assessments (CHNA) every 3 years. Best practices for CHNAs
      are still emerging and, along with growing economic pressures, contribute to
      uncertainty about the short- and long-term costs hospitals will face as a result
      of the ACA. PURPOSE: This article describes a community-based partnership
      coordinated by a nonprofit hospital and a consortium of academic institutions as
      a model for conducting a CHNA. KEY POINTS: Similar partnerships offer key
      advantages in complying with the ACA: local academic institutions are existing
      stakeholders in the community--they possess research expertise and have a vested
      interested in shaping implementation strategies to improve health; the process of
      collaborating itself helps to generate community resources, conceive of community
      health as a shared and iterative enterprise, and mobilize community partners in
      supporting long-term health priorities. CONCLUSIONS: No CHNA is ever perfect, but
      there are compelling reasons for nonprofit hospitals to seek community-based
      partnerships, not only because such partnerships comply with the law but, more
      importantly, because they hold great promise for linking the CHNA process and
      results to the health realities of local communities, ultimately bolstering
      community engagement while creating shared health priorities.

PMID- 25981431
TI  - Building capacity in disadvantaged communities: development of the community
      advocacy and leadership program.
AB  - BACKGROUND: Successful community groups have the capacity to mobilize community
      assets to address needs. Capacity-building education is integral to building
      competent communities. OBJECTIVES: A community-university team developed and
      pilot tested an education program for community advocates from disadvantaged
      neighborhoods with high chronic disease burden. METHODS: The Community Advocacy
      and Leadership Program (CALP) included eight monthly workshops, a mini-grant
      opportunity, and technical assistance. A nominal group with community health
      practitioners, focus group with community advocates, and a literature search
      comprised a triangulated educational needs assessment. A participating pretest
      with 35 community health practitioners guided curriculum refinement. Seven
      representatives from three community groups in a medically underserved South
      Carolina county participated in pilot implementation and evaluation. Qualitative
      and quantitative data informed the process and impact evaluation. RESULTS: The
      mean knowledge score at 1 month after the program was 77% (range, 52%-96%). The
      mean score on post-program self-assessment of skills improvement was 3.8 out of a
      possible 4.0 (range, 3.6-4.0). Two groups submitted successful community mini
      grant applications for playground improvements, and the third group successfully
      advocated for public funding of neighborhood park improvements. Participants
      reported favorable impressions and both personal and community benefits from
      participation. CONCLUSIONS: A community-university partnership successfully
      conducted a local educational needs assessment and developed and pilot tested a
      capacity development program within a CBPR partnership. Successes, challenges,
      and lessons learned will guide program refinement, replication, and
      dissemination.

PMID- 25981432
TI  - Stand against cancer: evaluating a breast and cervical cancer screening program
      for uninsured patients.
AB  - BACKGROUND: Stand Against Cancer (SAC) is a long-running, community-based,
      organization-led program that addresses breast and cervical cancer disparities.
      Managed by Access Community Health Network (ACCESS), ongoing program evaluation
      reports on program performance over 5 years and public health implications.
      OBJECTIVES: To reduce disparities by making free cancer screening readily
      accessible to uninsured women and by connecting women to nurse case management to
      resolve abnormal screening results. Evaluation supports program management by
      assessing operations and outcomes. METHODS: Health center staff completes patient
      applications that start the clock to achieve a resolution for all women who
      screen. All women with abnormal screens are referred to nurse case management and
      entered into a database for tracking. Program evaluation tracks the extent to
      which the predominantly minority women successfully reach resolution points,
      specifically the return of screening results and diagnostic resolution of
      abnormal results, including initiation of treatment. RESULTS: A 5-year average of
      10,400 women received SAC-supported screening at ACCESS. Through nurse case
      management, 90% of patients with abnormal screening results received a diagnosis.
      Women increasingly return and screen in subsequent years, contributing to a lower
      rate of late-stage cancers. Uninsured patients receiving SAC screening made
      additional nonscreening visits. Evaluation determined that SAC participant
      outcomes approximate or exceed a comparable national cohort and that program
      outcomes demonstrate effectiveness, equity, and optimality. CONCLUSIONS: Annual
      SAC evaluation illustrates that removing access barriers and providing nurse case
      management support to patients with abnormal results produced non-dispasrate
      outcomes for uninsured women.

PMID- 25981434
TI  - Use of Pipeline Embolization Devices for treatment of a direct carotid-cavernous
      fistula.
AB  - BACKGROUND: The use of minimally porous endoluminal devices (MPEDs) such as the
      Pipeline Embolization Device (PED) has been described for the treatment of brain
      aneurysms. The benefit of using MPEDs to assist embolization of a direct high
      flow carotid cavernous fistula resulting from a ruptured cavernous carotid artery
      aneurysm is not well documented. METHODS: We describe our experience with
      deploying a tailored multidevice PED construct across the cavernous internal
      carotid artery (ICA) wall defect in combination with transarterial coil
      embolization using the "jailed microcatheter" technique. RESULTS: A 59-year-old
      woman presented with acute left-sided ophthalmoplegia. Diagnostic cerebral
      angiography demonstrated a ruptured giant cavernous carotid aneurysm with
      fistulous outflow via the ipsilateral left superior ophthalmic vein and into the
      pterygoid venous plexi bilaterally. Via the Marksman microcatheter, a total of
      three PEDs measuring 4.5 mm * 18 mm, 4.5 mm * 20 mm, and 4.75 mm * 16 mm were
      telescoped within the ICA across the aneurysm neck. Coiling of the aneurysm
      fundus and cavernous sinus via the "jailed" Rapidtransit microcatheter was
      subsequently achieved. A 2-year follow-up digital subtraction angiography (DSA)
      demonstrated stable obliteration of the aneurysm and the fistula, coincident with
      complete resolution of the patient's symptoms. CONCLUSIONS: Based on our long
      term clinical and angiographic results, we advocate that the presented method be
      a valid treatment option for selected cases.

PMID- 25981433
TI  - The emergence of Clostridium difficile PCR-ribotype 001 in Slovakia.
AB  - PURPOSE: The purpose of this study was to determine the incidence of Clostridium
      difficile infections (CDI) and to characterise the isolates in 14 departments of
      ten academic hospitals in Slovakia. METHODS: During a one-month study (September
      2012) all unformed stool samples were investigated using a rapid test to detect
      the presence of GDH and toxins A/B. Positive samples were cultured anaerobically
      and C. difficile isolates were characterised by ribotyping, multiple-locus
      variable-number tandem repeats analysis, and gyrA, rpoB and ermB investigation.
      RESULTS: A total of 194 unformed stool samples were investigated and 38 (19.6 %)
      had a positive rapid test. Of 38 samples, 27 revealed a positive result for GDH
      and free toxins A/B in the stool, and 11 samples only for the presence of GDH.
      The mean CDI incidence in 2012 was 5.2 cases per 10,000 patient bed-days. Twenty
      C. difficile isolates were available for molecular analysis; seventeen belonged
      to PCR-ribotype 001 (85 %) whereas the remaining three isolates were identified
      as PCR-ribotypes 017, 078 and 449. MLVA of the PCR-ribotype 001 isolates
      identified two clonal complexes and a close genetic relatedness between isolates
      from six different hospitals. Molecular analysis of antibiotic-resistance
      determinants revealed the presence of ermB gene encoding resistance to the MLSB
      group of antibiotics in 90 % of isolates, and Thr82Ile amino acid substitution in
      the gyrA gene associated with resistance to fluoroquinolones in 85 % of isolates.
      CONCLUSIONS: We conclude that C. difficile PCR-ribotype 001 is the predominant
      PCR-ribotype in Slovakia with a strong potential for clonal spread and
      development of multidrug resistance.

PMID- 25981435
TI  - Removal of large hydatid cysts with balloon-assisted modification of Dowling's
      method: technical report.
AB  - BACKGROUND: Delivery of hydatid cysts, especially large ones, without rupture is
      very important and there is still no 100% successful method. METHODS: After the
      hydatid cyst was reached, starting near the surface working around the cyst
      toward the base, a Foley probe was advanced and, in the region of desired
      dissection, the balloon of the Foley probe was inflated, and adhesion bands were
      freed to allow dissection. CONCLUSIONS: We believe our balloon-aided dissection
      technique is a method that increases the chances of delivering hydatid cysts,
      with no calcification and secondary infection, without rupture.

PMID- 25981437
TI  - Neospora caninum: the First Demonstration of the Enteroepithelial Stages in the
      Intestines of a Naturally Infected Dog.
AB  - A 1.5-month-old Kangal breed puppy from a dairy cattle farm died after showing
      severe diarrhoea and incoordination. Necropsy examination revealed multifocal
      pulmonary consolidation and necrosis and fibrinohaemorrhagic enteritis.
      Microscopically, there was necrotic and purulent bronchopneumonia, myocarditis
      and non-purulent encephalitis. In the jejunum and ileum there was villous atrophy
      and crypt hyperplasia with oocyst-like and schizont-like structures in the
      epithelia. Immunohistochemically, Neospora caninum antigen was detected in
      association with the intestinal protozoal structures, degenerative neurons and
      areas of necrosis in the lungs and heart. Polymerase chain reaction confirmed
      that the organism was N. caninum and not Toxoplasma gondii. The seroprevalence
      for N. caninum was 74.2% (49/66 animals) for the cattle and 57.1% (4/7 animals)
      for dogs on this farm. This report documents fatal systemic neosporosis and
      enteroepithelial stages of N. caninum in a naturally infected puppy. To the
      authors' knowledge, this is the first definition of intestinal neosporosis in a
      naturally infected dog as well as the first evidence of fatal canine neosporosis
      in Turkey. 

PMID- 25981436
TI  - Identification and characterization of nuclear and nucleolar localization signals
      in 58-kDa microspherule protein (MSP58).
AB  - BACKGROUND: MSP58 is a nucleolar protein associated with rRNA transcription and
      cell proliferation. Its mechanism of translocation into the nucleus or the
      nucleolus, however, is not entirely known. In order to address this lack, the
      present study aims to determine a crucial part of this mechanism: the nuclear
      localization signal (NLS) and the nucleolar localization signal (NoLS) associated
      with the MSP58 protein. RESULTS: We have identified and characterized two NLSs in
      MSP58. The first is located between residues 32 and 56 (NLS1) and constitutes
      three clusters of basic amino acids (KRASSQALGTIPKRRSSSRFIKRKK); the second is
      situated between residues 113 and 123 (NLS2) and harbors a monopartite signal
      (PGLTKRVKKSK). Both NLS1 and NLS2 are highly conserved among different vertebrate
      species. Notably, one bipartite motif within the NLS1 (residues 44-56) appears to
      be absolutely necessary for MSP58 nucleolar localization. By yeast two-hybrid,
      pull-down, and coimmunoprecipitation analysis, we show that MSP58 binds to
      importin alpha1 and alpha6, suggesting that nuclear targeting of MSP58 utilizes a
      receptor-mediated and energy-dependent import mechanism. Functionally, our data
      show that both nuclear and nucleolar localization of MSP58 are crucial for
      transcriptional regulation on p21 and ribosomal RNA genes, and context-dependent
      effects on cell proliferation. CONCLUSIONS: Results suggest that MSP58 subnuclear
      localization is regulated by two nuclear import signals, and that proper
      subcellular localization of MSP58 is critical for its role in transcriptional
      regulation. Our study reveals a molecular mechanism that controls nuclear and
      nucleolar localization of MSP58, a finding that might help future researchers
      understand the MSP58 biological signaling pathway.

PMID- 25981440
TI  - Quality assessment of cataract surgery in Denmark - risk of retinal detachment
      and postoperative endophthalmitis.

PMID- 25981439
TI  - Can endophthalmitis be prevented?

PMID- 25981441
TI  - Long-Term Follow-Up of the Cheilectomy for Degenerative Joint Disease of the
      First Metatarsophalangeal Joint.
AB  - Cheilectomy is the surgical resection of 20% to 30% of the dorsal metatarsal head
      and proximal phalanx. The present retrospective study evaluated the long-term
      efficacy of aggressive cheilectomy to address degenerative joint disease of the
      first metatarsophalangeal joint. To our knowledge, this is the second longest
      duration study to date to evaluate the long-term efficacy of the cheilectomy
      procedure, with a mean follow-up period of 7.14 years (range 39 weeks to 14.87
      years). The mean patient age was 55.71 +/- 9.51 years, and 37 (65%) of the
      patients were female. Age, sex, foot type, and preoperative radiographic
      parameters of hallux rigidus were also evaluated and correlated. The mean
      percentage of success with this operation was 87.69%. Of the 58 patients, 51
      (87.93%) experienced no limitations in their daily activities. Only 2 patients
      (3.33%) subsequently required subsequent arthrodesis. The results of the present
      study suggest that cheilectomy offers long-term satisfaction for patients with
      hallux rigidus and is an acceptable alternative to the joint destructive
      procedure of first metatarsophalangeal arthrodesis. 

PMID- 25981442
TI  - Non-Necrotizing Streptococcal Cellulitis as a Cause of Acute, Atraumatic
      Compartment Syndrome of the Foot: A Case Report.
AB  - Acute compartment syndrome is widely accepted as a surgical emergency. Most cases
      of acute compartment syndrome occur after high-energy trauma, especially crush
      injuries. We present a unique case of acute, atraumatic compartment syndrome of
      the foot associated with infectious cellulitis. A 53-year-old male, with a
      medical history significant for human immunodeficiency virus, presented to the
      emergency department secondary to an insidious onset of intense foot pain,
      swelling, and an inability to bear weight on the affected extremity. He had no
      history of recent trauma. He was admitted to the hospital because of a suspected
      infection and subsequently was given intravenous antibiotics. During the
      admission, he developed a severe infection, and blood cultures demonstrated
      growth of group A streptococcus. No abscess or hematoma was identified on
      magnetic resonance imaging or during exploratory surgery. The findings from
      intraoperative cultures were negative. Despite proper medical care for his
      infection, the lower extremity pain worsened; therefore, compartmental pressures
      were obtained at the bedside. Multiple compartment pressures were measured and
      were >40 mm Hg. Compartment syndrome was diagnosed, and the patient was taken to
      the operating room for emergent fasciotomies. Surgical release of the medial,
      lateral, interosseous, and adductor compartments revealed copious amounts of
      serosanguinous drainage. Again, no definitive hematoma or purulence was
      identified. The patient's symptoms resolved after the fasciotomies, and he healed
      uneventfully. Our case highlights the need to consider acute compartment syndrome
      in the differential diagnosis for pain out of proportion to the clinical
      situation, even when a traditional etiology is absent.

PMID- 25981443
TI  - Psychometric evaluation of the Hospital Anxiety and Depression Scale 3 months
      after acute lung injury.
AB  - PURPOSE: To conduct a psychometric evaluation of the Hospital Anxiety and
      Depression Scale (HADS) and to evaluate associations of 2 measures of
      psychological distress with the HADS Anxiety (HADS-A) and HADS Depression (HADS
      D) subscales in acute lung injury (ALI) survivors. MATERIALS AND METHODS: We used
      3-month post-ALI follow-up data from 151 participants in a multisite prospective
      cohort study to evaluate the internal consistency and structure of the HADS
      subscales and items, respectively. We used Spearman rho correlations and other
      statistics to relate the 3-level version of the EuroQol-5D (EQ-5D-3L)
      anxiety/depression item and Medical Outcomes Study Short Form-36 (SF-36) "mental
      health"-related domains to the HADS subscales. RESULTS: Internal consistency was
      good for each of the HADS subscales (alpha >= .70). Exploratory factor analysis
      revealed a 2-factor structure (anxiety and depression). The EQ-5D-3L item and the
      SF-36 mental health-related domain scores were associated with HADS-A (rho = 0.54
      and -0.48 to -0.70, respectively) and HADS-D (rho = 0.41 and -0.48 to -0.52,
      respectively) scores (all P < .01). The relationship between the SF-36 mental
      health domain score and the HADS-A subscale score was particularly strong (rho = 
      0.70, P < .01). CONCLUSIONS: When evaluated in ALI survivors, the HADS has good
      internal consistency and a 2-factor structure. The HADS subscales were
      substantially correlated with the EQ-5D-3L anxiety/depression item and SF-36
      mental health-related domain scores, suggesting convergent validity for these
      measures of psychological distress in ALI survivors.

PMID- 25981444
TI  - The duration of hospitalization before review by the rapid response team: A
      retrospective cohort study.
AB  - PURPOSE: The purpose of this study is to compare cases of rapid response team
      (RRT) review for early deterioration (<48 hours after admission), intermediate
      deterioration (48 to <168 hours after admission), late deterioration (>=168 hours
      after admission), and cardiac arrest and to determine the association between
      duration of hospitalization before RRT review and mortality. METHODS: This is a
      retrospective cohort study of RRT cases from a single hospital over 5 years (2009
      2013) using administrative data and data for the first RRT attendance of each
      hospital episode. RESULTS: Of 2843 RRT cases, 971 (34.2%) were early
      deterioration, 917 (32.3%) intermediate, 775 (27.3%) late, and 180 (6.3%) cardiac
      arrest. Compared with early deterioration patients, late deterioration patients
      were older (median, 71 vs 69 years; P = .005), had a higher Charlson comorbidity
      index (median, 2 vs 1; P < .001), more often had RRT review for respiratory
      distress (32.5% vs 23.5%; P < .001), more often received RRT-initiated not for
      resuscitation orders (8.4% vs 3.9%; P < .001), less often were discharged
      directly home (27.9% vs 58.4%; P < .001), and more often died in hospital (30.6%
      vs 12.8%; P < .001). Compared with early deterioration and adjusted for
      confounders, the odds ratio of death in hospital for late deterioration was 2.36
      (1.81-3.08; P < .001). CONCLUSIONS: Late deterioration is frequently encountered
      by the RRT and, compared with early deterioration, is associated with greater
      clinical complexity and a worse hospital outcome.

PMID- 25981445
TI  - Comparative evaluation of Acute Physiology and Chronic Health Evaluation II and
      Sequential Organ Failure Assessment scoring systems in patients admitted to the
      cardiac intensive care unit.
AB  - PURPOSE: To assess and compare the performance of Acute Physiology and Chronic
      Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA)
      scores in the cardiac intensive care unit (CICU). METHODS: A single-center,
      prospective cohort study in a CICU admitting patients with acute cardiovascular
      diseases was conducted. Both APACHE II and SOFA were calculated on admission. The
      area under the receiver operating characteristic curve (AUC) was used to evaluate
      the discriminative ability for predicting CICU survival, hospital survival, and
      survival 6 months after hospital discharge. Goodness of fit was assessed using
      the Hosmer-Lemeshow and the Brier scores. All analyses were conducted separately
      for the patients with acute coronary syndrome. RESULTS: Of the 300 consecutively
      admitted patients, 206 had acute coronary syndrome. Both scores exhibited good
      discriminative ability (AUC range, 0.84-0.92), and their AUCs did not differ
      significantly. The Hosmer-Lemeshow test P values were numerically higher (.151
      .949 vs .033-.531), and the Brier score closer to zero (0.0864-0.1570 vs 0.1039
      0.1264) for APACHE II compared with SOFA score models. The Acute Physiology and
      Chronic Health Evaluation was the best single risk factor for CICU mortality
      (odds ratio, 1.24; 95% confidence interval, 1.13-1.37; P < .001). CONCLUSION:
      Both APACHE II and SOFA scores have good and comparable discriminative ability
      for predicting outcome. Calibration and accuracy indices are superior for APACHE
      II.

PMID- 25981446
TI  - Lineage specific evolution of the VNTR composite retrotransposon central domain
      and its role in retrotransposition of gibbon LAVA elements.
AB  - BACKGROUND: VNTR (Variable Number of Tandem Repeats) composite retrotransposons -
      SVA (SINE-R-VNTR-Alu), LAVA (LINE-1-Alu-VNTR-Alu), PVA (PTGR2-VNTR-Alu) and FVA
      (FRAM-VNTR-Alu) - are specific to hominoid primates. Their assembly, the
      evolution of their 5' and 3' domains, and the functional significance of the
      shared 5' Alu-like region are well understood. The central VNTR domain, by
      contrast, has long been assumed to represent a more or less random collection of
      30-50 bp GC-rich repeats. It is only recently that it attracted attention in the
      context of regulation of SVA expression. RESULTS: Here we provide evidence that
      the organization of the VNTR is non-random, with conserved repeat unit (RU)
      arrays at both the 5' and 3' ends of the VNTRs of human, chimpanzee and orangutan
      SVA and gibbon LAVA. The younger SVA subfamilies harbour highly organized
      internal RU arrays. The composition of these arrays is specific to the
      human/chimpanzee and orangutan lineages, respectively. Tracing the development of
      the VNTR through evolution we show for the first time how tandem repeats evolve
      within the constraints set by a functional, non-autonomous non-LTR
      retrotransposon in two different families - LAVA and SVA - in different hominoid
      lineages. Our analysis revealed that a microhomology-driven mechanism mediates
      expansion/contraction of the VNTR domain at the DNA level. Elements of all four
      VNTR composite families have been shown to be mobilized by the autonomous LINE1
      retrotransposon in trans. In case of SVA, key determinants of mobilization are
      found in the 5' hexameric repeat/Alu-like region. We now demonstrate that in
      LAVA, by contrast, the VNTR domain determines mobilization efficiency in the
      context of domain swaps between active and inactive elements. CONCLUSIONS: The
      central domain of VNTR composites evolves in a lineage-specific manner which
      gives rise to distinct structures in gibbon LAVA, orangutan SVA, and
      human/chimpanzee SVA. The differences observed between the families and lineages
      are likely to have an influence on the expression and mobilization of the
      elements.

PMID- 25981447
TI  - Development of the Liver in Alpaca (Vicugna pacos): A Microscopic and Macroscopic
      Description.
AB  - South American camelids have several biological, morphological and behavioural
      adaptations that allow them to live in geographical areas dominated by high
      altitudes. The liver has hematopoietic functions during the prenatal life, which
      could be modified in response to the unfavorable habitat. However, there are no
      previous data on the prenatal development of the liver in these species. In the
      present work, a study on the macroscopic and microscopic morphology of the liver
      of the alpaca during ontogeny was performed. Forty-one animals ranging in age
      from 20 days of embryonic development to adults were studied. Macroscopic and
      microscopic observations were performed on samples subjected to different
      techniques. Less than 7-g specimens were studied with stereoscopic magnifying
      glass. The general characteristics of the prenatal liver are similar to those of
      other mammals, and the structures related to hematopoietic function follow an
      ontogenic pattern similar to that of previously studied precocial species.
      However, there are differences in morphology when compared to descriptions for
      the Old World camelids, including the absence of relation between the caudate
      lobe and the right kidney and the lack of interlobular connective tissue. 

PMID- 25981448
TI  - iPSCs as a major opportunity to understand and cure age-related diseases.
AB  - Cellular senescence plays an important role in the process of aging and is often
      associated with age-related diseases. Senescence was originally considered as a
      barrier to cell reprogramming, however we developed a strategy to overcome this
      hurdle and derive induced pluripotent stem cells (iPSCs) from senescent cells and
      cells from centenarians. Furthermore we showed that the newly generated iPSCs
      could be re-differentiated into fully rejuvenated cells. That has increased the
      known beneficial properties of iPSCs to include them as a tool to model age
      related diseases or even to cure them through cell therapy. In this review, we
      describe the hallmarks of cellular senescence before presenting how we
      reprogrammed aged and senescent cells into iPSCs and obtained rejuvenated re
      differentiated cells. Finally, we take an interest in the way iPSCs can be used
      to understand and cure age-related diseases and we present their advantages for
      patient-specific therapy. 

PMID- 25981449
TI  - Application of the KeratinoSensTM assay for assessing the skin sensitization
      potential of agrochemical active ingredients and formulations.
AB  - Assessment of skin sensitization potential is an important component of the
      safety evaluation process for agrochemical products. Recently, non-animal
      approaches including the KeratinoSensTM assay have been developed for predicting
      skin sensitization potential. Assessing the utility of the KeratinoSensTM assay
      for use with multi-component mixtures such as agrochemical formulations has not
      been previously evaluated and is a significant need. This study was undertaken to
      evaluate the KeratinoSensTM assay prediction potential for agrochemical
      formulations. The assay was conducted for 8 agrochemical active ingredients (AIs)
      including 3 sensitizers (acetochlor, meptyldinocap, triclopyr), 5 non-sensitizers
      (aminopyralid, clopyralid, florasulam, methoxyfenozide, oxyfluorfen) and 10
      formulations for which in vivo sensitization data were available. The
      KeratinoSensTM correctly predicted the sensitization potential of all the AIs.
      For agrochemical formulations it was necessary to modify the standard assay
      procedure whereby the formulation was assumed to have a common molecular weight.
      The resultant approach correctly predicted the sensitization potential for 3 of 4
      sensitizing formulations and all 6 non-sensitizing formulations when compared to
      in vivo data. Only the meptyldinocap-containing formulation was misclassified, as
      a result of high cytotoxicity. These results demonstrate the promising utility of
      the KeratinoSensTM assay for evaluating the skin sensitization potential of
      agrochemical AIs and formulations. 

PMID- 25981450
TI  - Bone morphogenetic protein/retinoic acid inducible neural-specific protein
      (brinp) expression during Danio rerio development.
AB  - Prototype Membrane Attack Complex/Perforin (MACPF) superfamily proteins such as
      complement and perforin play crucial roles in immune defense where they drive
      lytic pore formation. However, it is evident that other MACPF family members are
      important in the central nervous system. For example, three bone morphogenetic
      protein/retinoic acid inducible neural-specific proteins (Brinp1, Brinp2 and
      Brinp3) are present in developing and mature mammalian neurons, but their
      molecular function is unknown. In this study we have identified and cloned full
      length orthologues of all three human brinps from Danio rerio (zebrafish).
      Zebrafish and human brinps show very high sequence conservation, and the
      chromosomal loci are syntenic. We also identified two additional brinp3
      paralogues at a separate locus in the zebrafish genome. The spatiotemporal
      expression of all five zebrafish brinps was determined by RT-PCR and whole mount
      RNA in situ hybridisation. Each brinp is expressed broadly in the developing
      nervous system at early stages (24 hours post fertilisation), but localises to
      specific structures in older embryos (48-72 hpf), as has been reported in mice.
      The conserved structures and spatiotemporal expression patterns of brinps
      reported in this study suggest that zebrafish will be useful for generating loss
      of function phenotypes to assist in determining the molecular role of these
      proteins. 

PMID- 25981451
TI  - Minimal Hammerhead Ribozymes with Uncompromised Catalytic Activity.
AB  - We report here that a single additional trans-Hoogsteen base-pairing interaction
      in the minimal hammerhead ribozyme transforms an RNA sequence possessing
      typically modest catalytic activity into one possessing greatly enhanced
      catalytic activity that is instead typical of full-length natural hammerhead RNAs
      that have additional extensive tertiary contact interactions. Formation of this
      additional base-pairing interaction requires only that the substrate RNA sequence
      contains a U at a position seven nucleotides 3' to the cleavage site. No
      additions or changes are required in the minimal hammerhead ribozyme enzyme
      strand sequence (providing that the naturally occurring GUGA tetraloop of Stem II
      is maintained). This finding unambiguously demonstrates that a single Hoogsteen
      base-pairing interaction, in full-length hammerheads possessing this interaction,
      is sufficient for stabilizing the ribozyme active site, including alignment of
      the attacking nucleophile for the required inline hammerhead ribozyme reaction
      mechanism. This finding also implies that the idiosyncratic arrays of additional
      tertiary contacts observed in all naturally occurring full-length hammerhead
      sequences have evolved to prevent deleterious alternative pairing interactions
      within the context of the variety of natural sequences arising in vivo. Finally,
      this finding greatly simplifies and rationalizes the design of fast-cleaving
      engineered synthetic ribozymes as RNA nucleolytic reagents and as subjects for
      enzyme kinetics and mechanistic investigations. 

PMID- 25981452
TI  - Virologically suppressed patients with asymptomatic and symptomatic HIV
      associated neurocognitive disorders do not display the same pattern of immune
      activation.
AB  - OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and
      age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive
      impairment in HIV-infected patients and explored differences according to
      clinical severity. METHODS: Post hoc analysis of data from two prospective
      cohorts of HIV-infected patients randomly selected to undergo neuropsychological
      tests was performed. Test scores were adjusted for age, gender and education.
      Inclusion criteria were undetectable viral load and stable treatment for at least
      6 months. Subjects with HIV-associated dementia were excluded. Patients were
      divided into an unimpaired group, a group with asymptomatic neurocognitive
      disorder (ANI) and a group with symptomatic HIV-associated neurocognitive
      disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic
      and background parameters, immune activation markers and the CD4:CD8 ratio were
      recorded. RESULTS: Two hundred patients were included in the study. The mean age
      was 52 years, 78% were male, the mean CD4 count was 624 cells/MUL, the mean nadir
      CD4 count was 240 cells/MUL, 27% were hepatitis C virus (HCV)-coinfected, the
      mean duration of HIV infection was 16 years, and the mean time on current
      combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of
      subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a
      CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/MUL [odds
      ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23).
      Multinominal logistic regression showed that, in comparison with the unimpaired
      group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62),
      longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI
      group differed from the unimpaired group only for education level. CONCLUSIONS:
      Aviraemic patients with sHAND did not display the same pattern of immune
      activation as subjects with ANI, suggesting that the underlying
      pathophysiological mechanisms could be different.

PMID- 25981453
TI  - The emerging role of hypoxia-inducible factor-2 involved in chemo/radioresistance
      in solid tumors.
AB  - The hypoxic condition is a common feature that negatively impacts the efficacy of
      radio- and chemotherapy in solid tumors. Hypoxia-inducible factors (HIF-1, 2, 3)
      predominantly regulate the adaptation to hypoxia at the cellular or organismal
      level. HIF-2 is one of the three known alpha subunits of HIF transcription
      factors. Previous studies have shown that HIF-1 is associated with chemotherapy
      failure. Accumulating evidence in recent years suggests that HIF-2 also
      contributes to chemo/radioresistance in solid tumors. Despite sharing similar
      structures, HIF-1alpha and HIF-2alpha had highly divergent and even opposing
      roles in solid tumors under hypoxic conditions. Recent studies have also implied
      that HIF-2alpha had a role in chemo/radioresistance through different mechanisms,
      at least partly, compared to HIF-1alpha. The present paper summarizes the
      function of HIF-2 in chemo/radioresistance in solid tumors as well as some of its
      novel mechanisms that contributed to this pathological process.

PMID- 25981454
TI  - The hallmarks of castration-resistant prostate cancers.
AB  - Prostate cancer has become a real public health issue in industrialized
      countries, mainly due to patients' relapse by castration-refractory disease after
      androgen ablation. Castration-resistant prostate cancer is an incurable and
      highly aggressive terminal stage of prostate cancer, seriously jeopardizing the
      patient's quality of life and lifespan. The management of castration-resistant
      prostate cancer is complex and has opened new fields of research during the last
      decade leading to an improved understanding of the biology of the disease and the
      development of new therapies. Most advanced tumors resistant to therapy still
      maintain the androgen receptor-pathway, which plays a central role for survival
      and growth of most castration-resistant prostate cancers. Many mechanisms induce
      the emergence of the castration resistant phenotype through this pathway. However
      some non-related AR pathways like neuroendocrine cells or overexpression of anti
      apoptotic proteins like Hsp27 are described to be involved in CRPC progression.
      More recently, loss of expression of tumor suppressor gene, post-transcriptional
      modification using miRNA, epigenetic alterations, alternatif splicing and gene
      fusion became also hallmarks of castration-resistant prostate cancer. This review
      presents an up-to-date overview of the androgen receptor-related mechanisms as
      well as the latest evidence of the non-AR-related mechanisms underlying
      castration-resistant prostate cancer progression.

PMID- 25981455
TI  - Tailored electrical conductivity, electromagnetic shielding and thermal transport
      in polymeric blends with graphene sheets decorated with nickel nanoparticles.
AB  - Electromagnetic interference shielding (EMI) materials were designed using PC
      (polycarbonate)/SAN [poly(styrene-co-acrylonitrile)] blends containing few
      layered graphene nanosheets decorated with nickel nanoparticles (G-Ni). The
      graphene nanosheets were decorated with nickel nanoparticles via the uniform
      nucleation of the metal salt precursor on graphene sheets as the substrate. In
      order to localize the nanoparticles in the PC phase of the PC/SAN blends, a two
      step mixing protocol was adopted. In the first step, graphene sheets were mixed
      with PC in solution and casted into a film, followed by dilution of these PC
      master batch films with SAN in the subsequent melt extrusion step. The dynamic
      mechanical properties, ac electrical conductivity, EMI shielding effectiveness
      and thermal conductivity of the composites were evaluated. The G-Ni nanoparticles
      significantly improved the electrical and thermal conductivity in the blends. In
      addition, a total shielding effectiveness (SET) of -29.4 dB at 18 GHz was
      achieved with G-Ni nanoparticles. Moreover, the blends with G-Ni exhibited an
      impressive 276% higher thermal conductivity and 29.2% higher elastic modulus with
      respect to the neat blends. 

PMID- 25981456
TI  - Research capacity and culture of the Victorian public health allied health
      workforce is influenced by key research support staff and location.
AB  - OBJECTIVE: The aim of the present study was to identify and understand the self
      rated research capacity and culture of the allied health workforce. METHODS. The
      present study was a cross-sectional survey. The Research Capacity and Culture
      tool was disseminated to all Victorian public health allied health departments.
      General demographic data were also collected, including the presence of an
      organisational allied health research lead. RESULTS: Five hundred and twenty
      fully completed surveys were returned by participants; all allied health
      disciplines and all grades were represented. One hundred and eighty-six
      participants had an organisational allied health research lead and 432 were
      located in a metropolitan-based health service. There were significant
      differences (P < 0.05) within all organisational and team research skills between
      those with and without a research lead, together with those in different service
      locations (metropolitan vs non-metropolitan). Higher self-ratings in individual
      research skills (P < 0.05) were primarily associated with more senior and
      metropolitan-located clinicians. CONCLUSION: The allied health workforce
      identifies as a group that is ready to build the evidence to support clinical
      practice yet requires a whole-systems approach to do so. The results of the
      present study suggest that the development of key people to build capacity at a
      higher organisational level has a flow-down effect on research capacity and
      culture.

PMID- 25981457
TI  - Differential Reactivity and the Within-person Job Stressor-Satisfaction
      Relationship.
AB  - An experience sampling methodology was used to study the direct and conditional
      within-person relationship between job stressors and job satisfaction. One
      hundred and one full-time administrative staff completed momentary measures of
      job stressors and job satisfaction three times a day on six different workdays
      over a 3-week period (N = 1818 observations). Multilevel random coefficients
      models were specified, and the results suggest that within-person stressors are
      negatively related to within-person job satisfaction. These results stand when
      controlling for the effects of time, demographics, work characteristics, baseline
      levels of job stressors and satisfaction, and between-person effects of job
      stressors. Furthermore, consistent with the differential reactivity model, the
      results suggest that the observed within-person stressors-satisfaction
      relationship is conditional upon locus of control and positive affect. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 25981459
TI  - Theoretical study on the effects of a 4,6-O-diacetal protecting group on the
      stability of ion pairs from D-mannopyranosyl and D-glucopyranosyl triflates.
AB  - Ion pair formation from 2,3-di-O-methyl-4,6-O-formylidene-alpha-D-mannopyranosyl
      triflate alphaTMan and its D-glucopyranosyl counterpart alphaTGlc was
      investigated at the DFT(M06-2X) level of theory, for the purpose of clarifying
      the effects of the 4,6-tethering on the structure and stability of alpha- and
      beta-contact ion pairs and solvent-separated ion pairs at -78  degrees C. In both
      mannopyranosyl and glucopyranosyl triflates, the 4,6-O-formylidene group
      destabilized (4)H3-type conformers of the alpha-contact ion pairs, rendering B2,5
      types the exclusive conformers for this species. The B2,5-like alpha-contact ion
      pair from alphaTMan was 3.5 kcal/mol more stable than that from alphaTGlc,
      probably due to the stabilizing effect by the planar O-5-C-1-C-2-O-2 dihedral
      angle of the former. This difference in stability of the alpha-contact ion pair
      between the mannopyranosyl and glucopyranosyl series gives insights into the
      mechanisms underlying the reported experimental observation that highly beta
      selective mannosylation can be achieved with 4,6-O-diacetal mannopyranosyl
      donors.

PMID- 25981458
TI  - Troponin T3 regulates nuclear localization of the calcium channel Cavbeta1a
      subunit in skeletal muscle.
AB  - The voltage-gated calcium channel (Cav) beta1a subunit (Cavbeta1a) plays an
      important role in excitation-contraction coupling (ECC), a process in the
      myoplasm that leads to muscle-force generation. Recently, we discovered that the
      Cavbeta1a subunit travels to the nucleus of skeletal muscle cells where it helps
      to regulate gene transcription. To determine how it travels to the nucleus, we
      performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA
      library and identified an interaction with troponin T3 (TnT3), which we
      subsequently confirmed by co-immunoprecipitation and co-localization assays in
      mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting
      domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244
      aa) and Cavbeta1a NH2-terminus (1-99 aa), respectively. The double fluorescence
      assay in C2C12 cells co-expressing TnT3/DsRed and Cavbeta1a/YFP shows that TnT3
      facilitates Cavbeta1a nuclear recruitment, suggesting that the two proteins play
      a heretofore unknown role during early muscle differentiation in addition to
      their classical role in ECC regulation.

PMID- 25981460
TI  - Mathematical optimization of contrast concentration for T1-weighted spoiled
      gradient echo imaging.
AB  - PURPOSE: To develop and validate closed form mathematical expressions that
      predict the optimal contrast agent concentration for the maximum T1-weighted
      spoiled gradient echo (SGRE) signal. THEORY AND METHODS: Gadolinium and iron
      based contrast agents can have significant transverse relaxivity that leads to
      signal dropout with increasing contrast agent concentration. A mathematical
      expression for the "optimal" contrast agent concentration where recovery of
      longitudinal magnetization is offset by increasing transverse signal decay was
      derived. Expressions for the maximum possible SGRE signal were also derived.
      Three phantoms were constructed, each with varying concentrations of one of the
      following three agents: gadoteridol, gadobenate dimeglumine, and ferumoxytol.
      After measuring the longitudinal and transverse relaxivity of the three agents,
      the SGRE signal was measured in the phantoms over a wide range of flip angles and
      echo times. RESULTS: Excellent qualitative agreement between the SGRE signal
      behavior, optimal concentration, and optimal flip angle were observed between
      experimental measurements and theoretical predictions. CONCLUSION: This work
      provides validated mathematical expressions for contrast enhanced T1-weighted
      SGRE imaging and may provide guidance for contrast dosing and injection
      protocols, as well as for novel pulse sequence design.

PMID- 25981461
TI  - Concordance and limits between transcutaneous and arterial carbon dioxide
      pressure in emergency department patients with acute respiratory failure: a
      single-center prospective observational study.
AB  - INTRODUCTION: Transcutaneous CO2 (PtCO2) is a continuous and non-invasive measure
      recommended by scientific societies in the management of respiratory distress.
      The objective of this study is to evaluate the correlation between PtCO2 and
      blood pressure of CO2 (PaCOv) by blood gas analysis in emergency patients with
      dyspnoea and to determine the factors that interfere in this correlation.
      METHODS: From January to June 2014, all patients admitted to resuscitation room
      of the emergency department targeted for arterial blood gases were included
      prospectively. A sensor measuring the PtCO2 was attached to the ear lobe of the
      patient before the gas analysis. Anamnesis, clinical and laboratory parameters
      were identified. RESULTS: 90 patients with dyspnoea were included (with 104 pairs
      of measurements), the median age was 79 years [69-85]. The correlation between
      PtCO2 and PaCO2 was R(2)= 0.83 (p <0.001) but became lower for values of PaCO2>60
      mm Hg. The mean bias (+/-SD) between the two methods of measurement (Bland-Altman
      analysis) was -1.4 mm Hg (+/-7.7) with limits of agreement of -16.4 to 13.7 mm
      Hg. In univariate analysis, PaO2 interfered in this correlation. After
      multivariate analysis, the temperature (OR = 3.01, 95% CI = 1.16-7.09) and the
      PaO 2 (OR = 1.22, 95% CI = 1.02-1.47) were found to be significant. CONCLUSIONS:
      In patients admitted in emergency unit for acute respiratory failure, there is a
      significant correlation between PaCO2 and PtCO2, mainly for values below 60 mm
      Hg. The two limiting factors of use are hyperthermia and users training.

PMID- 25981463
TI  - Investigating CRISPR RNA Biogenesis and Function Using RNA-seq.
AB  - The development of deep sequencing technology has greatly facilitated
      transcriptome analyses of both prokaryotes and eukaryotes. RNA-sequencing (RNA
      seq), which is based on massively parallel sequencing of cDNAs, has been used to
      annotate transcript boundaries and revealed widespread antisense transcription as
      well as a wealth of novel noncoding transcripts in many bacteria. Moreover, RNA
      seq is nowadays widely used for gene expression profiling and about to replace
      hybridization-based approaches such as microarrays. RNA-seq has also informed
      about the biogenesis and function of CRISPR RNAs (crRNAs) of different types of
      bacterial RNA-based CRISPR-Cas immune systems. Here we describe several studies
      that employed RNA-seq for crRNA analyses, with a particular focus on a
      differential RNA-seq (dRNA-seq) approach, which can distinguish between primary
      and processed transcripts and allows for a genome-wide annotation of
      transcriptional start sites. This approach helped to identify a new crRNA
      biogenesis pathway of Type II CRISPR-Cas systems that involves a trans-encoded
      small RNA, tracrRNA, and the host factor RNase III. 

PMID- 25981464
TI  - In Vitro Co-reconstitution of Cas Protein Complexes.
AB  - CRISPR-Cas systems employ diverse and often multimeric CRISPR-associated (Cas)
      protein effector complexes to mediate antiviral defense. The elucidation of the
      mechanistic details and the protein interaction partners requires production of
      recombinant Cas proteins. However, these proteins are often produced as inactive
      inclusion bodies. Here, we present a detailed protocol for the isolation and
      purification of insoluble Cas proteins. Guidelines for their solubilization via
      co-reconstitution strategies and procedures to upscale the production of soluble
      multimeric Cas protein complexes are provided. 

PMID- 25981462
TI  - Mass cytometry as a platform for the discovery of cellular biomarkers to guide
      effective rheumatic disease therapy.
AB  - The development of biomarkers for autoimmune diseases has been hampered by a lack
      of understanding of disease etiopathogenesis and of the mechanisms underlying the
      induction and maintenance of inflammation, which involves complex activation
      dynamics of diverse cell types. The heterogeneous nature and suboptimal clinical
      response to treatment observed in many autoimmune syndromes highlight the need to
      develop improved strategies to predict patient outcome to therapy and personalize
      patient care. Mass cytometry, using CyTOF(r), is an advanced technology that
      facilitates multiparametric, phenotypic analysis of immune cells at single-cell
      resolution. In this review, we outline the capabilities of mass cytometry and
      illustrate the potential of this technology to enhance the discovery of cellular
      biomarkers for rheumatoid arthritis, a prototypical autoimmune disease. 

PMID- 25981465
TI  - Analysis of CRISPR Pre-crRNA Cleavage.
AB  - We have examined the processing of precursor-clustered regularly interspaced
      short palindromic repeat (CRISPR) RNAs (pre-crRNAs) of the Type I CRISPR-Cas
      system by incubation of radiolabeled model RNAs with recombinant CRISPR
      associated (Cas) endoribonucleases, followed by denaturing polyacrylamide gel
      electrophoresis (PAGE) of the products. Determination of cleavage position is
      based on comparison with RNase T1 digestion and base hydrolysis products. The
      mechanism of cleavage is investigated by chemical and enzymatic characterization
      of the reaction products as well as by the demonstration that a specific 2'-deoxy
      substitution 5' to the scissile phosphate blocks endonucleolytic cleavage. 

PMID- 25981467
TI  - Computational Detection of CRISPR/crRNA Targets.
AB  - The CRISPR-Cas systems in bacteria and archaea provide protection by targeting
      foreign nucleic acids. The sequence of the "spacers" within CRISPR arrays
      specifically determines the targets in invader genomes. These spacers provide the
      short specific RNA nucleotide sequences within the guide crRNAs. In addition to
      complementarity in the spacer-target (protospacer) interaction, short flanking
      protospacer adjacent motifs (PAMs), or mismatching flanks have a discriminatory
      role in accurate target detection. Here, we describe a bioinformatic method,
      called CRISPRTarget, to use the sequence of a CRISPR array (e.g., predicted via
      CRISPRDetect/CRISPRDirection) to identify the foreign nucleic acids it targets. 

PMID- 25981468
TI  - High-Throughput CRISPR Typing of Mycobacterium tuberculosis Complex and
      Salmonella enterica Serotype Typhimurium.
AB  - Spoligotyping was developed almost 18 years ago and still remains a popular first
      lane genotyping technique to identify and subtype Mycobacterium tuberculosis
      complex (MTC) clinical isolates at a phylogeographic level. For other pathogens,
      such as Salmonella enterica, recent studies suggest that specifically designed
      spoligotyping techniques could be interesting for public health purposes.
      Spoligotyping was in its original format a reverse line-blot hybridization method
      using capture probes designed on "spacers" and attached to a membrane's surface
      and a PCR product obtained from clustered regularly interspaced short palindromic
      repeats (CRISPRs). Cowan et al. and Fabre et al. were the first to propose a high
      throughput Spoligotyping method based on microbeads for MTC and S. enterica
      serotype Typhimurium, respectively. The main advantages of the high-throughput
      Spoligotyping techniques we describe here are their low cost, their robustness,
      and the existence (at least for MTC) of very large databases that allow
      comparisons between spoligotypes from anywhere. 

PMID- 25981469
TI  - Spacer-Based Macroarrays for CRISPR Genotyping.
AB  - Macroarray-based analysis is a powerful and economic format to study variations
      in "clustered regularly interspaced short palindromic repeat (CRISPR)" loci in
      bacteria. To date, it was used almost exclusively for Mycobacterium tuberculosis
      and was named spoligotyping (spacer oligonucleotides typing). Here, we describe
      the pipeline of this approach that includes search of loci and selection of
      spacers, preparation of the membrane with immobilized probes and spoligotyping
      itself (PCR and reverse hybridization). 

PMID- 25981466
TI  - Annotation and Classification of CRISPR-Cas Systems.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas
      (CRISPR-associated proteins) is a prokaryotic adaptive immune system that is
      represented in most archaea and many bacteria. Among the currently known
      prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented
      complexity and diversity. Classification of CRISPR-Cas variants that would
      capture their evolutionary relationships to the maximum possible extent is
      essential for comparative genomic and functional characterization of this
      theoretically and practically important system of adaptive immunity. To this end,
      a multipronged approach has been developed that combines phylogenetic analysis of
      the conserved Cas proteins with comparison of gene repertoires and arrangements
      in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas
      systems into three distinct types and ten subtypes for each of which signature
      genes have been identified. Comparative genomic analysis of the CRISPR-Cas
      systems in new archaeal and bacterial genomes performed over the 3 years elapsed
      since the development of this classification makes it clear that new types and
      subtypes of CRISPR-Cas need to be introduced. Moreover, this classification
      system captures only part of the complexity of CRISPR-Cas organization and
      evolution, due to the intrinsic modularity and evolutionary mobility of these
      immunity systems, resulting in numerous recombinant variants. Moreover, most of
      the cas genes evolve rapidly, complicating the family assignment for many Cas
      proteins and the use of family profiles for the recognition of CRISPR-Cas subtype
      signatures. Further progress in the comparative analysis of CRISPR-Cas systems
      requires integration of the most sensitive sequence comparison tools, protein
      structure comparison, and refined approaches for comparison of gene
      neighborhoods. 

PMID- 25981470
TI  - Analysis of crRNA Using Liquid Chromatography Electrospray Ionization Mass
      Spectrometry (LC ESI MS).
AB  - Mass spectrometry is a powerful tool for characterizing RNA. Here we describe a
      method for the identification and characterisation of crRNA using liquid
      chromatography interfaced with electrospray ionization mass spectrometry (LC ESI
      MS). The direct purification of crRNA from the Cascade-crRNA complex was
      performed using denaturing ion pair reverse phase chromatography. Following
      purification of the crRNA, the intact mass was determined by LC ESI MS. Using
      this approach, a significant reduction in metal ion adduct formation of the crRNA
      was observed. In addition, RNase mapping of the crRNA was performed using RNase
      digestion in conjunction with liquid chromatography tandem MS analysis. Using the
      intact mass of the crRNA, in conjunction with RNase mapping experiments enabled
      the identification and characterisation of the crRNA, providing further insight
      into crRNA processing in a number of type I CRISPR-Cas systems. 

PMID- 25981471
TI  - Rapid Multiplex Creation of Escherichia coli Strains Capable of Interfering with
      Phage Infection Through CRISPR.
AB  - In Escherichia coli, acquisition of new spacers in the course of CRISPR-Cas
      adaptation is dramatically stimulated by preexisting partial matches between a
      bacterial CRISPR cassette spacer and a protospacer sequence in the DNA of the
      infecting bacteriophage or plasmid. This phenomenon, which we refer to as
      "priming," can be used for very simple and rapid construction of multiple E. coli
      strains capable of targeting, through CRISPR interference, any phage or plasmid
      of interest. Availability of such strains should allow rapid progress in the
      analysis of CRISPR-Cas system function against diverse mobile genetic elements. 

PMID- 25981472
TI  - Exploring CRISPR Interference by Transformation with Plasmid Mixtures:
      Identification of Target Interference Motifs in Escherichia coli.
AB  - Plasmid transformation into a bacterial host harboring a functional CRISPR-Cas
      system targeting a sequence in the transforming molecule can be specifically
      hindered by CRISPR-mediated interference. In this case, measurements of
      transformation efficacy will provide an estimation of CRISPR activity. However,
      in order to standardize data of conventional assays (using a single plasmid in
      the input DNA sample), transformation efficiencies have to be compared to those
      obtained for a reference molecule in independent experiments. Here we describe
      the use of a transforming mixture of plasmids that includes the non-targeted
      vector as an internal reference to obtain normalized data which are unbiased by
      empirical variations. 

PMID- 25981473
TI  - Electrophoretic Mobility Shift Assay of DNA and CRISPR-Cas Ribonucleoprotein
      Complexes.
AB  - The Electrophoretic Mobility Shift Assay is a straightforward and inexpensive
      method for the determination and quantification of protein-nucleic acid
      interactions. It relies on the different mobility of free and protein-bound
      nucleic acid in a gel matrix during electrophoresis. Nucleic acid affinities of
      crRNA-Cas complexes can be quantified by calculating the dissociation constant
      (Kd). Here, we describe how two types of EMSA assays are performed using the
      Cascade ribonucleoprotein complex from Escherichia coli as an example.

PMID- 25981474
TI  - Expression and Purification of the CMR (Type III-B) Complex in Sulfolobus
      solfataricus.
AB  - Protein purification is an important technique that allows us to characterize the
      structural and biochemical properties of either an individual protein or a multi
      protein complex. However, expression and purification of one subunit of a complex
      in the absence of its binding partners has often proven difficult to achieve due
      to the issues such as instability and mis-folding. This is the case for the
      components of the CRISPR-Cas interference complexes, which degrade invading
      nucleic acids in a sequence homology-dependent manner in many prokaryotic
      species. Here, we describe the expression of a tandem-tagged subunit of the Type
      III-B (CMR) complex in Sulfolobus solfataricus and subsequent isolation and
      purification of the whole complex by affinity purification of the tagged subunit.

PMID- 25981475
TI  - Procedures for Generating CRISPR Mutants with Novel Spacers Acquired from Viruses
      or Plasmids.
AB  - CRISPR-Cas systems provide immunity in bacteria and archaea against nucleic acids
      in the form of viral genomes and plasmids, and influence their coevolution. The
      first main step of CRISPR-Cas activity is the immune adaptation through spacer(s)
      acquisition into an active CRISPR locus. This step is also mandatory for the
      final stage of CRISPR-Cas activity, namely interference. This chapter describes
      general procedures for studying the CRISPR adaptation step, accomplished by
      producing bacteriophage-insensitive mutants (BIMs) or plasmid-interfering mutants
      (PIMs) using various spacer acquisition analyses and experiments. Since each
      bacterial or archaeal species (and even strain) needs specific conditions to
      optimize the acquisition process, the protocols described below should be thought
      of as general guidelines and may not be applicable universally, without
      modification. Because Streptococcus thermophilus was used as the model system in
      the first published study on novel spacer acquisition and in many studies ever
      since, the protocols in this chapter describe specific conditions, media, and
      buffers that have been used with this microorganism. Details for other species
      will be given when possible, but readers should first evaluate the best growth
      and storage conditions for each bacterium-foreign element pair (named the
      procedure settings) and bear in mind the specificity and variability of CRISPR
      Cas types and subtypes. Also, we suggest to be mindful of the fact that some
      CRISPR-Cas systems are not "naturally" active in terms of the ability to acquire
      novel CRISPR spacers, and that some systems may require specific conditions to
      induce the CRISPR-Cas activity for spacer acquisition.

PMID- 25981476
TI  - Archaeal Viruses of the Sulfolobales: Isolation, Infection, and CRISPR Spacer
      Acquisition.
AB  - Infection of archaea with phylogenetically diverse single viruses, performed in
      different laboratories, has failed to activate spacer acquisition into host
      CRISPR loci. The first successful uptake of archaeal de novo spacers was observed
      on infection of Sulfolobus solfataricus P2 with an environmental virus mixture
      isolated from Yellowstone National Park (Erdmann and Garrett, Mol Microbiol
      85:1044-1056, 2012). Experimental studies of isolated genetic elements from this
      mixture revealed that SMV1 (S ulfolobus Monocauda Virus 1), a tailed spindle
      shaped virus, can induce spacer acquisition in CRISPR loci of Sulfolobus species
      from a second coinfecting conjugative plasmid or virus (Erdmann and Garrett, Mol
      Microbiol 85:1044-1056, 2012; Erdmann et al. Mol Microbiol 91:900-917, 2014).
      Here we describe, firstly, the isolation of archaeal virus mixtures from
      terrestrial hot springs and the techniques used both to infect laboratory strains
      with these virus mixtures and to obtain purified virus particles. Secondly, we
      present the experimental conditions required for activating SMV1-induced spacer
      acquisition in two different Sulfolobus species. 

PMID- 25981477
TI  - Using the CRISPR-Cas System to Positively Select Mutants in Genes Essential for
      Its Function.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR
      associated proteins (Cas) comprise a prokaryotic adaptive defense system against
      foreign nucleic acids. This defense is mediated by Cas proteins, which are guided
      by sequences flanked by the repeats, called spacers, to target nucleic acids.
      Spacers designed against the prokaryotic self chromosome are lethal to the
      prokaryotic cell. This self-killing of the bacterium by its own CRISPR-Cas system
      can be used to positively select genes that participate in this killing, as their
      absence will result in viable cells. Here we describe a positive selection assay
      that uses this feature to identify E. coli mutants encoding an inactive CRISPR
      Cas system. The procedure includes establishment of an assay that detects this
      self-killing, generation of transposon insertion mutants in random genes, and
      selection of viable mutants, suspected as required for this lethal activity. This
      procedure enabled us to identify a novel gene, htpG, that is required for the
      activity of the CRISPR-Cas system. The procedures described here can be adjusted
      to various organisms to identify genes required for their CRISPR-Cas activity. 

PMID- 25981478
TI  - Analysis of nuclease activity of Cas1 proteins against complex DNA substrates.
AB  - Cas1 genes encode the signature protein of the CRISPR/Cas system, which is
      present in all CRISPR-containing organisms. Recently, Cas1 proteins (together
      with Cas2) have been shown to be essential for the formation of new spacers in
      Escherichia coli, and purified Cas1 proteins from Pseudomonas aeruginosa and E.
      coli have been shown to possess a metal-dependent endonuclease activity. Here we
      describe the protocols for the analysis of nuclease activity of purified Cas1
      proteins against various DNA substrates including Holliday junctions and other
      intermediates of DNA recombination and repair. 

PMID- 25981479
TI  - Characterizing Metal-Dependent Nucleases of CRISPR-Cas Prokaryotic Adaptive
      Immunity Systems.
AB  - CRISPRs (clustered regularly interspaced short palindromic repeats), together
      with the nearby CRISPR-associated (cas) operon, constitute a prokaryotic RNA
      based adaptive immune system against exogenous genetic elements. Here, we
      describe nuclease assays that are useful for characterizing the substrate
      specific function of CRISPR-associated protein Cas2. We also provide methods for
      characterizing the stoichiometry and affinity between Cas2 and divalent metal
      ions using isothermal titration calorimetry (ITC). 

PMID- 25981480
TI  - Cas3 nuclease-helicase activity assays.
AB  - Cas3 is a signature protein of the type I CRISPR-Cas systems and typically
      contains HD phosphohydrolase and Superfamily 2 (SF2) helicase domains. In the
      type I CRISPR-Cas systems Cas3 functions as a slicer that provides foreign DNA
      degradation. Biochemical analysis indicate that Cas3 of the Streptococcus
      thermophilus DGCC7710 (St-Cas3) CRISPR4 system is a single-stranded DNA nuclease
      which also possesses a single-stranded DNA-stimulated ATPase activity, which is
      coupled to unwinding of DNA/DNA and RNA/DNA duplexes in 3' to 5' direction. The
      interplay between the nuclease and ATPase/helicase activities of St-Cas3 results
      in DNA degradation. Here, we describe assays for monitoring of St-Cas3 nuclease,
      ATPase and helicase activities in a stand-alone form and in the presence of the
      Cascade ribonucleoprotein complex. These assays can be easily adapted for
      biochemical analysis of Cas3 proteins from different microorganisms. 

PMID- 25981481
TI  - Chemical and Enzymatic Footprint Analyses of R-Loop Formation by Cascade-crRNA
      Complex.
AB  - Cascade-crRNA complexes mediate the identification of the invading foreign DNA
      and initiate its neutralization by formation of an R-loop (RNA-induced DNA-loop)
      at the crRNA-complementary sequence (protospacer). After initial unspecific
      binding to the double-stranded DNA, Cascade-crRNA complex slides along the DNA to
      find the protospacer. Once the target site is detected, the crRNA hybridizes to
      the complementary strand with subsequent displacement of the non-complementary
      strand to form an R-loop structure. Here, we describe how Cascade-DNA complexes
      and the Cascade-induced strand separation can be characterized in detail by
      combining chemical and enzymatic footprint analyses. Selective modification of
      unpaired thymines by permanganate (KMnO4) and the specific cleavage of single
      stranded DNA by Nuclease P1 can be used to probe an R-loop formation by Cascade.
      Localization of the Cascade-crRNA complex on the DNA can be achieved by an
      Exonuclease III protection assay. 

PMID- 25981482
TI  - Creation and Analysis of a Virome: Using CRISPR Spacers.
AB  - Advances in sequencing technology have allowed for the study of complex and
      previously unexplored microbial and viral populations; however, linking host
      phage partners using in silico techniques has been challenging. Here, we describe
      the flow-through for creation of a virome, and its subsequent analysis with the
      viral assembly and analysis module "Viritas," which we have recently developed.
      This module allows for binning of contigs based on tetranucleotide frequencies,
      putative phage-host partner identification by CRISPR spacer matching, and
      identification of ORFs. 

PMID- 25981483
TI  - Targeted Mutagenesis in Zebrafish Using CRISPR RNA-Guided Nucleases.
AB  - In recent years, the zebrafish has become a critical contributor to various areas
      of biomedical research, advancing our fundamental understanding of biomedicine
      and helping discover candidate therapeutics for human diseases. Nevertheless, to
      further extend the power of this important model organism requires a robust and
      simple-to-use genome editing platform that will enable targeted gene knockouts
      and introduction of specific mutations identified in human diseases into the
      zebrafish genome. We describe here protocols for creating insertion or deletion
      (indel) mutations or precise sequence modifications in zebrafish genes using
      customizable CRISPR-Cas9 RNA-guided nucleases (RGNs). These methods can be easily
      implemented in any lab and may also potentially be extended for use in other
      organisms. 

PMID- 25981484
TI  - Precise Genome Editing of Drosophila with CRISPR RNA-Guided Cas9.
AB  - The readily programmable CRISPR-Cas9 system is transforming genome engineering.
      We and others have adapted the S. pyogenes CRISPR-Cas9 system to precisely
      engineer the Drosophila genome and demonstrated that these modifications are
      efficiently transmitted through the germline. Here we provide a detailed protocol
      for engineering small indels, defined deletions, and targeted insertion of
      exogenous DNA sequences within one month using a rapid DNA injection-based
      approach. 

PMID- 25981485
TI  - Targeted Transcriptional Repression in Bacteria Using CRISPR Interference
      (CRISPRi).
AB  - Clustered regularly interspersed short palindromic repeats (CRISPR) interference
      (CRISPRi) is a powerful technology for sequence-specifically repressing gene
      expression in bacterial cells. CRISPRi requires only a single protein and a
      custom-designed guide RNA for specific gene targeting. In Escherichia coli,
      CRISPRi repression efficiency is high (~300-fold), and there are no observable
      off-target effects. The method can be scaled up as a general strategy for the
      repression of many genes simultaneously using multiple designed guide RNAs. Here
      we provide a protocol for efficient guide RNA design, cloning, and assay of the
      CRISPRi system in E. coli. In principle, this protocol can be used to construct
      CRISPRi systems for gene repression in other species of bacteria. 

PMID- 25981486
TI  - MuTAnT: a family of Mutator-like transposable elements targeting TA
      microsatellites in Medicago truncatula.
AB  - Transposable elements (TEs) are mobile DNA segments, abundant and dynamic in
      plant genomes. Because their mobility can be potentially deleterious to the host,
      a variety of mechanisms evolved limiting that negative impact, one of them being
      preference for a specific target insertion site. Here, we describe a family of
      Mutator-like DNA transposons in Medicago truncatula targeting TA microsatellites.
      We identified 218 copies of MuTAnTs and an element carrying a complete ORF
      encoding a mudrA-like transposase. Most insertion sites are flanked by a variable
      number of TA tandem repeats, indicating that MuTAnTs are specifically targeting
      TA microsatellites. Other TE families flanked by TA repeats (e.g. TAFT elements
      in maize) were described previously, however we identified the first putative
      autonomous element sharing that characteristics with a related group of short non
      autonomous transposons. 

PMID- 25981487
TI  - Comorbidity as a predictor of mortality and mobility after hip fracture.
AB  - AIM: To determine mortality and mobility rates after hip fracture. METHODS: A
      prospective study (n = 199 patients) was carried out in the Health Care Center of
      A Coruna (Spain) during the period between January 2009 and December 2011. A
      descriptive study, and Cox and logistic regression analysis were carried out.
      Informed consent and ethical review board approval were obtained (code 2010/120
      CEIC Galicia). RESULTS: The patients' mean age was 82.5 +/- 8.4 years and 76%
      were female. The average Charlson Comorbidity Index score was 6.1 +/- 2.1.
      Creatinine clearance <60 mL/min/1.73 m(2) was 44%. The probability of survival 6
      months after hip fracture was 89.2% and the survival rate at 12 months was 81.4%.
      Cox regression analysis showed that the indicator that most influenced mortality
      rate was comorbidity (HR = 1.133; P = 0.020) and age approaching borderline
      statistical significance (HR = 1.034; P = 0.064). The Parker Mobility Score
      decreased significantly (P < 0.001) after hip fracture. Before fracture, 19% of
      the patients were able to get about the house, 26% were able to get out of the
      house and 55% were able to go shopping. After hip fracture (90 days), the
      percentages changed to 56.2%, 19.1% and 24.7%, respectively (P < 0.001). After
      taking into account age, sex, type of fracture, surgical delay, previous fracture
      and comorbidity, the only indicator capable of predicting incapacity to walk was
      comorbidity. CONCLUSIONS: Comorbidity is the best predictor of mortality and
      mobility after hip fracture. Geriatr Gerontol Int 2016; 16: 561-569.

PMID- 25981488
TI  - Incidence, direct costs and duration of hospitalization of patients hospitalized
      with community acquired pneumonia: A nationwide retrospective claims database
      analysis.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is one of the most common acute
      infections associated with a substantial clinical and economic burden. There have
      been few studies assessing incidence rate, duration of hospitalization, and costs
      of hospitalized CAP by age and care-setting. METHODS: A retrospective study was
      conducted using a nationwide Dutch database containing healthcare claims data of
      16.7 million inhabitants. Patients with at least one claim with a discharge
      diagnosis of CAP between January 2008 and December 2011 were selected. The main
      outcome measures considered were the incidence rate, duration of hospitalization,
      and the direct costs of hospitalized CAP stratified by age and care-setting.
      RESULTS: In total, 195,372 CAP cases were included in the analysis resulting in
      an average incidence of 295 per 100,000 population per year. Sixty-three percent
      (123,357) of the included patients were hospitalized for 1 or more nights, of
      which 5.9% (n=7241) spent at least one night in the Intensive Care Unit (ICU).
      Overall, these 123,357 patients spent 824,985 days in the hospital of which
      48,324 were spent on the ICU. The mean duration of hospitalization of ICU
      patients and general ward patients was 15.2 days and 6.2 days, respectively. The
      total costs related to all 195,372 CAP episodes during these 4 years were ?711
      million, with the majority (76%) occurring among those aged 50 years and older.
      Median (and mean) costs were dependent on age and type of care with costs ranging
      from ?344 (?482) per episode for 0-9 year olds treated in the outpatient hospital
      setting up to ?10,284 (?16,374) per episode for 50-64 year olds admitted to the
      ICU. CONCLUSION: There is a large variation in terms of incidence, disease burden
      and costs across different age groups and the treatment setting. Effective
      interventions, targeted at older adults, to prevent pneumonia could reduce the
      (financial) burden due to pneumonia.

PMID- 25981489
TI  - Recombinant lactobacillus expressing G protein of spring viremia of carp virus
      (SVCV) combined with ORF81 protein of koi herpesvirus (KHV): A promising way to
      induce protective immunity against SVCV and KHV infection in cyprinid fish via
      oral vaccination.
AB  - Spring viremia of carp virus (SVCV) and koi herpesvirus (KHV) are highly
      contagious and pathogenic to cyprinid fish, causing enormous economic losses in
      aquaculture. Although DNA vaccines reported in recent years could induce
      protective immune responses in carps against these viruses via injection, there
      are a number of consequences and uncertainties related to DNA vaccination.
      Therefore, more effective and practical method to induce protective immunity such
      as oral administration would be highly desirable. In this study, we investigated
      the utilities of a genetically engineered Lactobacillus plantarum (L. plantarum)
      coexpressing glycoprotein (G) of SVCV and ORF81 protein of KHV as oral vaccine to
      induce protective immunity in carps via oral vaccination. The surface-displayed
      recombinant plasmid pYG-G-ORF81 was electroporated into L. plantarum, giving rise
      to LP/pYG-G-ORF81, where expression and localization of G-ORF81 fusion protein
      from the LP/pYG-G-ORF81 was identified by SDS-PAGE, Western blotting and
      immunofluorescence assay. Bait feed particles containing the LP/pYG-G-ORF81 were
      used as vaccine to immunize carps via gastrointestinal route. Compared to control
      groups, the carps orally immunized with the LP/pYG-G-ORF81 were induced
      significant levels of immunoglobulin M (IgM), and its immunogenicity was
      confirmed by viral loads reduction detected by PCR assay after virus challenge
      followed by an effective protection rate 71% in vaccinated carps and 53% in
      vaccinated koi until at days 65 post challenge, respectively. Our study here
      demonstrates, for the first time, the ability of recombinant L. plantarum as oral
      vaccine against SVCV and KHV infection in carps, suggesting a practical
      multivalent strategy for the control of spring viremia of carp and koi
      herpesvirus disease.

PMID- 25981490
TI  - Impact of Hepatitis A vaccination with a two-dose schedule in Panama: Results of
      epidemiological surveillance and time trend analysis.
AB  - PURPOSE: In April 2007, Panama introduced Hepatitis A universal vaccination using
      a two-dose schedule (Havrix((r))junior; GSK Vaccines, Belgium). We assessed the
      impact of this hepatitis A vaccine three years after it was recommended for
      universal mass vaccination in Panama. MATERIALS AND METHODS: Hepatitis A
      vaccination impact was assessed using two different approaches. The first
      approach used retrospective data (incidence and number of cases for all age
      groups), collected from the passive surveillance of the Epidemiologic
      Surveillance System of the Ministry of Health of hepatitis A and unspecified
      hepatitis before (2000-2006) and after (2008-2010) introduction of hepatitis A
      vaccine. The second approach was a prospective hospital-based active surveillance
      for hepatitis cases conducted in subjects (0-14 years) during 2009-2011 at three
      sentinel hospitals in Panama. RESULTS: Overall, the annual incidence of hepatitis
      A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per
      100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects.
      In comparison to the mean baseline period (2000-2006), there was an 82% mean
      reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified
      hepatitis) after vaccine introduction (2008-2010) in all age groups. In the
      hospital-based surveillance (2009-2011), of the 42 probable viral hepatitis A
      cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of
      these confirmed cases, two belonged to the targeted vaccine group (1-4 years) but
      were not vaccinated. CONCLUSIONS: Our study suggests that the introduction of two
      dose hepatitis A vaccines in Panama has contributed to the reduction in the
      incidence of overall hepatitis-related outcomes for all age groups, suggesting
      herd protection. Additional monitoring is required to document a sustained long
      term effect.

PMID- 25981491
TI  - Evidence of light-dependent magnetic compass orientation in urodele amphibian
      larvae.
AB  - Experiments were conducted to investigate whether larval palmate newts undertake
      orientation toward or away from the home shoreline (y-axis orientation) using the
      geomagnetic field to steer the most direct route, and if they accomplish this
      task through a light-dependent magnetoreception mechanism similar to that found
      in anuran tadpoles and adult newts. Larval palmate newts trained and then tested
      under full-spectrum light showed bimodal magnetic compass orientation that
      coincided with the magnetic direction of the trained y-axis. In contrast, larvae
      trained under long-wavelength (>=500nm) light and then tested under full-spectrum
      light displayed bimodal orientation perpendicular to the trained y-axis
      direction. These results offer evidence for the use of magnetic compass cues in
      orienting urodele amphibian larvae, and provide additional support for the light
      dependent magnetoreception mechanism since they are in complete agreement with
      earlier studies showing that the observed 90 degrees  shift in the direction of
      magnetic compass orientation under long-wavelength light (>=500nm) is due to a
      direct effect of light on the underlying magnetoreception mechanism. This study
      is the first to provide evidence of a light-dependent magnetic compass in larval
      urodeles. 

PMID- 25981492
TI  - Non-motor symptoms burden in treated and untreated early Parkinson's disease
      patients: argument for non-motor subtypes.
AB  - BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) occurring at an early stage of
      Parkinson's disease (PD) may impair quality of life more than motor symptoms.
      This study aimed to evaluate the severity of overall NMS profile and burden of
      NMSs in early PD patients, treated (time since confirmed diagnosis of 5 years or
      less) or drug naive (DN). METHODS: Cross-sectional data from an ongoing
      multicentre study (16 sites) were obtained and specifically an NMS data set from
      validated scales was analysed in treated and DN PD patients. RESULTS: A full data
      set was available in 234 unique early PD patients. Of them, there were 170
      treated (63.5% males, mean age 68.2 years) and 64DN patients (64.1% males, mean
      age 66.5 years). Compared to DN patients the time since confirmed diagnosis was
      significantly longer in treated PD patients (1.9 years vs. 3.7 years, P < 0.001).
      Fatigue (57.7%), urinary urgency (57.1%), nocturia (55.3%), memory difficulties
      (51.2%) and urinary frequency (48.8%) were the most prevalent NMSs amongst
      treated PD, whereas DN PD reported most frequently sadness (57.8%), fatigue
      (57.8%), lightheadedness (53.1%), memory difficulties (48.4%) and urinary urgency
      (46.9%). CONCLUSIONS: Our results suggest that NMSs are dominant in the untreated
      and early phase of PD causing a considerable burden. This warrants investigation
      of the issue of NMS subtyping within PD.

PMID- 25981493
TI  - Infant developmental milestones and adult intelligence: A 34-year follow-up.
AB  - BACKGROUND: A number of studies suggest a positive association between faster
      infant motor development and intellectual function in childhood and adolescence.
      However, studies investigating the relationship between infant motor development
      and intelligence in adulthood are lacking. AIMS: To investigate whether age at
      achievement of 12 motor developmental milestones was associated with adult
      intelligence and to evaluate the influence of sex, parental social status,
      parity, mother's cigarette consumption in the last trimester, gestational age,
      birthweight, and birth length on this association. METHODS: Mothers of 9125
      children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones
      during the child's first year of life. A subsample of the cohort comprising 1155
      individuals participated in a follow-up when they were aged 20-34 years and were
      administered the Wechsler Adult Intelligence Scale (WAIS). Associations between
      motor developmental milestones and IQ were analysed by multiple linear regression
      adjusting for potential confounding factors. RESULTS: Later acquisition of infant
      developmental milestones was associated with lower subsequent IQ, and the
      majority of significant associations were found for Performance IQ. Correlations
      were generally small (r < 0.10), but significant interactions were found between
      parental social status and age of attaining developmental milestones, with
      associations being significantly stronger in the offspring of lower social status
      parents. The effects remained significant after adjusting for possible
      confounding factors. CONCLUSION: This is the first study to find significant
      interactions with parental social status, thereby suggesting that associations
      between early motor development and intelligence are stronger in infants of low
      social status parents.

PMID- 25981494
TI  - The second to fourth digit ratio (2D:4D) in Saudi boys with autism: A potential
      screening tool.
AB  - BACKGROUND: Autism is a neurodevelopment disorder with a strikingly higher
      prevalence in boys than girls. There are many theories regarding this gender
      bias, and prenatal exposure to high levels of fetal testosterone (FT) may be a
      predisposing factor. The second to fourth digit ratio (2D:4D) is the only
      indirect measure that reflects this association postnatally. Thus, this study
      measured the lengths of the index finger (2D) and the ring finger (4D) and
      calculated the 2D:4D ratio. Subsequently, this ratio was used to indirectly
      determine the potential prenatal exposure to high levels of FT in autistic
      children. METHODS: This case-control study was conducted with 60 male children
      with 31 individuals having classic-onset autism and 29 individuals serving as age
      matched, healthy controls. The lengths of both the index (2D) and the ring (4D)
      fingers of the right hand of both autism and control groups were obtained using a
      scanner and the 2D:4D ratio was calculated. RESULTS: The 2D:4D ratio in the
      current study was significantly lower in boys with autism compared to the
      controls (p <= 0.001). CONCLUSIONS: This study demonstrates a significantly lower
      2D:4D ratio in Saudi boys with autism, which indirectly suggests that these boys
      were exposed to high levels of prenatal FT. Accordingly, prenatal exposure to
      high levels of FT is a risk factor for the development of autism, and the
      postnatal measurement of the 2D:4D ratio could be a potential screening tool.

PMID- 25981495
TI  - The effect of co-morbid depression and anxiety on the course and outcome of
      alcohol outpatient treatment: A naturalistic prospective cohort study.
AB  - BACKGROUND: Studies examining the effect of alcohol treatment among patients with
      alcohol use disorders (AUD) and co-morbid depression and/or anxiety are few and
      show inconsistent, but mainly negative drinking outcomes. AIMS: To describe the
      prevalence of anxiety and depression among Danish patients seeking treatment for
      an AUD, and to investigate the influence of psychiatric co-morbidity on the
      course and effect of treatment. METHOD: A consecutive sample of 363 outpatients
      with an AUD diagnosis according to the ICD-10 Diagnostic Criteria for Research
      was assessed by the means of the Addiction Severity Index at treatment start and
      276 (76%) followed up after 1 year. RESULTS: 15.7% of the patients suffered from
      depression and 12.7% from anxiety at baseline. Both patients with or without co
      morbidity had improved on drinking outcome measures at follow-up with medium to
      large effect sizes. No difference was found between patients with and without co
      morbidity. CONCLUSION: In contrast to the majority of prior studies, this study
      provides evidence that depression and anxiety do not have an effect on alcohol
      treatment. However, because of the naturalistic setting, a number of limitations
      should be taken into consideration interpreting the results.

PMID- 25981496
TI  - Considerations for Nanosciences in Food Science and Nutrition: "Enhanced Food
      Properties".
AB  - The agro-food industries are one of the biggest manufacturing sectors worldwide
      with a turnover of US$4 trillion per year. Within the last decades, nanoscience
      has opened-up fantastic ways to challenge new sub-universes for exploring the
      interactions between physical, chemical and biological systems as well as agro
      food and nutrition sectors. Among these potentials, there is the enhancement of
      food properties and constituents such as nanoparticulate delivery systems, food
      safety and food biosecurity. In the recent years, many patents were launched for
      edible coating agents, essential oils and emulsifiers, including agrochemical
      active ingredients, nanomaterials for agriculture, horticulture, aquaculture, and
      smart packaging materials. The aim of this review was to search for the recent
      applications of nanoscience in the agro-food science and nutrition area,
      including the launched patents in this field. 

PMID- 25981498
TI  - DNA Methylation and MicroRNA-Based Biomarkers for Risk of Type 2 Diabetes.
AB  - The rapidly increasing prevalence of type 2 diabetes (T2D) is motivating an
      intensive search for biomarkers to identify individuals at risk for developing
      the disease. It has been established that both genetic and environmental factors
      are influential in the progression to T2D. Currently, the number of genetic loci
      implicated in T2D susceptibility is more than 65 and together, these factors
      explain only about 10% of the risk. At this time, prediction models using genetic
      information do not perform substantially better than models based on routine
      clinical measures. The search for new biomarkers must integrate new, independent
      factors beyond the static genome that are influenced by environmental conditions.
      This search must also recognize the heterogeneity of T2D and seek new biomarkers
      of potential subtypes and confounding conditions such as obesity. Modulation of
      gene expression by epigenetic modifications and the action of microRNAs are being
      recognized as critical processes affecting T2D risk. This review provides an
      update on the current state of genetic biomarkers of T2D susceptibility and
      examines how epigenetic modulation of some new and established diabetes
      susceptibility genes can identify increased risk and provide biomarkers for early
      detection and therapeutic monitoring. 

PMID- 25981497
TI  - Developing a community-led SMS reporting tool for the rapid assessment of
      lymphatic filariasis morbidity burden: case studies from Malawi and Ghana.
AB  - BACKGROUND: Lymphoedema and hydrocoele are the two most common clinical
      manifestations of lymphatic filariasis (LF). In order to effectively target
      morbidity management strategies, more information is rapidly needed on morbidity
      burden across all endemic countries. The purpose of this study was to develop and
      test an SMS tool (MeasureSMS) which enables trained community-based health
      workers to report basic information on all cases they identified. METHODS: The
      tool was trialled in Chikwawa district, Malawi and Ahanta West district, Ghana in
      2014. Salaried health surveillance assistants (HSAs) identified and reported
      cases in Malawi whereas volunteer community health workers (CHWs) were used in
      Ghana. Health workers were trained in recognising lymphoedema and hydrocoeles and
      submitting individual case data using MeasureSMS, after which they undertook a LF
      morbidity survey. After the reporting period, a random sample of reported cases
      was visited by a physician to verify the health workers' diagnoses. The
      proportion of correctly diagnosed cases i.e. the positive predictive value (PPV)
      was then calculated. RESULTS: HSAs in Malawi successfully reported 256 unique
      cases by SMS from 107 communities (166 hydrocoele, 88 lymphoedema, 2 with both),
      resulting in an estimated adult prevalence of 17.7 per 10,000 and 33.0 per 10,000
      for lymphoedema and hydrocoele respectively. In Ghana, despite being less
      experienced in using SMS, CHWs successfully reported 360 unique cases by SMS from
      33 communities (169 hydrocoele, 185 lymphoedema, 6 with both), resulting in an
      estimated adult prevalence of 76.9 per 10,000 and 70.5 per 10,000 adults for
      lymphoedema and hydrocoele respectively. The verification exercise resulted in a
      PPV for lymphoedema and hydrocoele diagnosis of 90 % (n = 42, 95 % CI 76.5 -
      96.9) and 92 % (n = 49, 95 % CI 79.5 - 97.4) in Malawi and 94 % (n = 34, 95 % CI
      78.9 %-99.0 %) and 47 % (n = 59, 35.1 %-61.7 %) in Ghana, indicating that non
      invasive methods for diagnosing hydrocoeles needed to be further emphasised.
      CONCLUSIONS: The study concludes that given the appropriate education and tools,
      community-based health workers are exceptionally well-placed to participate in
      quantifying LF morbidity burden, and other NTDs with observable symptoms. This
      concept has the potential to enable national programmes to more effectively
      monitor their community impact in an efficient, timely and cost-effective way.

PMID- 25981499
TI  - Depression Associated with Diabetes: From Pathophysiology to Treatment.
AB  - Diabetes is a chronic and progressive syndrome commonly associated with several
      neuropsychiatric comorbities, of which depression is the most studied. The
      prevalence of depression is about two or three times higher in diabetic patients
      compared to the general population. It is believed that the diabetes - depression
      relation may be bidirectional, i.e., the depression can lead to diabetes and
      conversely diabetes could facilitate the emergence of depression. Depression is
      one of the most neglected symptoms in diabetic patients and is directly linked
      with lowering of quality of life. The treatment of depression in these patients
      is still quite ineffective and in many cases treatmentrefractory. Furthermore,
      some of the first choice drugs used to treat the depression affect the blood
      glucose control, aggravating the hyperglycemic state. These issues underscore the
      urgency in studies searching for new pharmacological targets for the treatment of
      depression associated with diabetes. For this, a better understanding of the
      pathophysiology that relates this comorbidity becomes critical. In this respect,
      this review will focus on some hypotheses that have been proposed to explain the
      mechanisms underlying depression associated with diabetes, highlighting the
      treatment options currently available and their limitations. Among these
      hypotheses, we will point out the hyperglycemia as a primary metabolic cause of
      the depression development, the involvement of the dysregulation of hypothalamic
      pituitary-adrenal (HPA) axis and of neurotransmitter systems, specially
      monoaminergic system. Besides, the role of oxidative stress, neuroinflammation
      and cell death, especially in hippocampus and prefrontal cortex, brain areas
      important for the mediation and modulation of emotional behavior will also be
      discussed. Finally, we will bring up the influence of the epigenetic regulation
      with respect to neuropsychiatric disorders. 

PMID- 25981500
TI  - Critical assessment of influenza VLP production in Sf9 and HEK293 expression
      systems.
AB  - BACKGROUND: Each year, influenza is responsible for hundreds of thousand cases of
      illness and deaths worldwide. Due to the virus' fast mutation rate, the World
      Health Organization (WHO) is constantly on alert to rapidly respond to emerging
      pandemic strains. Although anti-viral therapies exist, the most proficient way to
      stop the spread of disease is through vaccination. The majority of influenza
      vaccines on the market are produced in embryonic hen's eggs and are composed of
      purified viral antigens from inactivated whole virus. This manufacturing system,
      however, is limited in its production capacity. Cell culture produced vaccines
      have been proposed for their potential to overcome the problems associated with
      egg-based production. Virus-like particles (VLPs) of influenza virus are
      promising candidate vaccines under consideration by both academic and industry
      researchers. METHODS: In this study, VLPs were produced in HEK293 suspension
      cells using the Bacmam transduction system and Sf9 cells using the baculovirus
      infection system. The proposed systems were assessed for their ability to produce
      influenza VLPs composed of Hemagglutinin (HA), Neuraminidase (NA) and Matrix
      Protein (M1) and compared through the lens of bioprocessing by highlighting
      baseline production yields and bioactivity. VLPs from both systems were
      characterized using available influenza quantification techniques, such as single
      radial immunodiffusion assay (SRID), HA assay, western blot and negative staining
      transmission electron microscopy (NSTEM) to quantify total particles. RESULTS:
      For the HEK293 production system, VLPs were found to be associated with the cell
      pellet in addition to those released in the supernatant. Sf9 cells produced 35
      times more VLPs than HEK293 cells. Sf9-VLPs had higher total HA activity and were
      generally more homogeneous in morphology and size. However, Sf9 VLP samples
      contained 20 times more baculovirus than VLPs, whereas 293 VLPs were produced
      along with vesicles. CONCLUSIONS: This study highlights key production hurdles
      that must be overcome in both expression platforms, namely the presence of
      contaminants and the ensuing quantification challenges, and brings up the
      question of what truly constitutes an influenza VLP candidate vaccine.

PMID- 25981501
TI  - Distinct ethanol drinking microstructures in two replicate lines of mice selected
      for drinking to intoxication.
AB  - The High Drinking in the Dark (HDID) mice have been selectively bred for reaching
      high blood ethanol concentrations (BECs) following the limited access Drinking in
      the Dark (DID) test. We have shown previously that mice from the first HDID
      replicate line (HDID-1) drink in larger, but not longer, ethanol drinking bouts
      than the low-drinking HS/Npt control mice when consuming modest amounts in the
      DID test. Here, we assessed drinking microstructure in HDID-1 mice during binge
      like levels of ethanol intake using a lickometer system. Mice from both HDID
      replicates (HDID-1 and -2) and HS mice were also given three DID tests (single
      bottle ethanol, two-bottle choice and single-bottle saccharin) using a
      continuously recording BioDAQ system to determine whether there are selection
      dependent changes in drinking microstructure. Larger ethanol bout size in the
      HDID-1 mice than the HS mice was found to be due to a larger lick volume in these
      mice. HDID-1 and HDID-2 mice were also seen to have different drinking
      microstructures that both resulted in high intake and high BECs. The HDID-1 mice
      drank in larger ethanol bouts than HS, whereas HDID-2 mice drank in more frequent
      bouts. This pattern was also seen in two-bottle choice DID. The HDID-2 mice had a
      high bout frequency for all fluid types tested, whereas the large bout size
      phenotype of the HDID-1 mice was specific to alcohol. These findings suggest that
      selection for drinking to intoxication has resulted in two distinct drinking
      microstructures, both of which lead to high BECs and high ethanol intake. 

PMID- 25981502
TI  - In Vivo Imaging of Hypoxia in Atherosclerotic Plaques in Humans.

PMID- 25981503
TI  - The Functional Effects of Intramural Course of Coronary Arteries and its Relation
      to Coronary Atherosclerosis.
AB  - OBJECTIVES: This study observed hemodynamic consequences of myocardial bridging
      and its relation to coronary atherosclerosis. BACKGROUND: Myocardial bridging is
      seen as intramural course by computed tomography angiography (CTA) or systolic
      compression by invasive coronary angiography. Segments with myocardial bridging
      are in previous studies closely associated with proximal atherosclerotic plaques.
      METHODS: We prospectively studied 100 patients 63 +/- 7 years of age with
      intermediate likelihood of coronary artery disease. Segments with superficial (>1
      mm) or deep (>2 mm) intramural course were identified using CTA. Myocardial
      perfusion was studied by 15-Oxygen water positron emission tomography and
      systolic compression by invasive coronary angiography. RESULTS: Myocardial
      bridging was detected in 34 (34%) patients in 48 different vascular segments. Of
      these, 24 (50%) were deep and systolic compression was present in 14 (29%). In
      patients without obstructive coronary artery disease, myocardial stress perfusion
      distal to myocardial bridging was comparable with remote control regions (3.3 +/-
      0.9 ml/g/min vs. 3.3 +/- 0.7 ml/g/min, n = 24, p = 0.88). Stress perfusion was
      comparable in segments with and without systolic compression (3.0 +/- 0.9 vs. 2.7
      +/- 1.0 ml/g/min, p = 0.43). Atherosclerotic plaques were more frequent in
      proximal (71%) than myocardial bridging (7%) or distal (21%) segments. The
      presence of atherosclerosis and the average number of plaques were comparable in
      coronary arteries with and without myocardial bridging (73% vs. 60%, p = 0.14 and
      2.0 +/- 1.7 vs. 1.5 +/- 1.6, p = 0.06). Median Agatston coronary calcium score
      was not elevated in vessels with myocardial bridge (15 [interquartile range: 0,
      129] vs. 50 [interquartile range: 0, 241], p = 0.21). CONCLUSIONS: Myocardial
      bridging of coronary arteries is common on CTA, but only approximately one-third
      of these show systolic compression. Myocardial bridging is not associated with
      reduced myocardial perfusion during vasodilator stress. Atherosclerosis is
      located predominantly proximal to myocardial bridging but atherosclerotic burden
      and presence of vulnerable plaques were comparable.

PMID- 25981505
TI  - The Transmural Extent and Severity of Myocardial Hypoperfusion Predicts Long-Term
      Outcome in NSTEMI: An MDCT Study.
AB  - OBJECTIVES: The objective of this study was to test the hypothesis that the
      extent and severity of left ventricular myocardial hypoperfusion at rest, in
      addition to signs of left ventricular myocardial scar, are related to adverse
      long-term outcome in patients with non-ST-segment elevation myocardial infarction
      (NSTEMI). BACKGROUND: Multidetector computed tomography (MDCT) is a noninvasive
      test with a spatial resolution that allows for the assessment of transmural
      myocardial perfusion. In patients with suspected NSTEMI, the assessment of
      myocardial hypoperfusion could be clinically useful. METHODS: MDCT was performed
      at rest before invasive treatment in 396 patients with NSTEMI. The transmural
      involvement of left ventricular hypoperfusion, the presence of intramyocardial
      fat or calcification, a summed defect score adding the extent of left ventricular
      myocardial hypoperfusion (0 to 64 point scale), and the transmural attenuation
      ratio between the subendocardial and the subepicardial myocardium were assessed.
      The study endpoint was a combination of death and hospitalization due to heart
      failure. RESULTS: The median follow-up time of the study was 50 months, and the
      study endpoint was reached in 56 (15%) of the patients. In a Cox proportional
      hazards survival model with adjustments for known risk factors, both the summed
      defect score and transmural attenuation ratio were independently associated with
      adverse outcome (hazard ratio [HR]: 1.07; 95% confidence interval [CI]: 1.02 to
      1.11; p = 0.004 and HR: 0.61; 95% CI: 0.44 to 0.85; p = 0.003, respectively). The
      presence of intramyocardial fat or calcification was also associated with adverse
      outcome (HR: 3.5; 95% CI: 1.2 to 10.7; p = 0.03) when compared with patients
      without any perfusion defect. CONCLUSIONS: The extent and severity of left
      ventricular myocardial hypoperfusion at rest and signs of left ventricular
      myocardial scar assessed with MDCT before invasive treatment is strongly linked
      to adverse long-term outcome in patients with NSTEMI.

PMID- 25981504
TI  - Right Intraventricular Dyssynchrony in Idiopathic, Heritable, and Anorexigen
      Induced Pulmonary Arterial Hypertension: Clinical Impact and Reversibility.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of right
      intraventricular dyssynchrony, its determinants and prognostic impact in
      idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension.
      BACKGROUND: Right ventricular dyssynchrony has been described in pulmonary
      arterial hypertension, but no evidence is available on its prognostic impact and
      evolution after therapy. METHODS: In 83 consecutive therapy-naive patients, right
      ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking
      echocardiography calculating the standard deviation of the times to peak-systolic
      strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline
      (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test
      [6 MWT]), a second assessment was performed after 12 months or when clinical
      worsening occurred. RESULTS: Patients with right ventricular dyssynchrony (RV-SD4
      >18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and
      hemodynamic profile compared with patients <= 18 ms. Determinants of dyssynchrony
      included pulmonary vascular resistance, QRS duration, and right ventricular end
      diastolic area (r(2) = 0.38; p < 0.000001). At 12 months, 32.5% of patients
      presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year).
      Multivariable models for clinical worsening prediction showed that the addition
      of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac
      index) significantly increased the prognostic power of the model (0.74 vs. 0.81;
      p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating
      characteristic analysis identified RV-SD4 >= 23 ms as the best cutoff value for
      clinical worsening prediction (95% negative predictive value). At 12 months,
      normalization of dyssynchrony was achieved in patients with a large reduction of
      pulmonary vascular resistance (-42 +/- 4%). CONCLUSIONS: Right ventricular
      dyssynchrony is frequent in pulmonary arterial hypertension, is an independent
      predictor of clinical worsening, and might regress during effective treatments.

PMID- 25981506
TI  - Performance of CMR Methods for Differentiating Acute From Chronic MI.
AB  - OBJECTIVES: The purpose of this study was to assess the performance of cardiac
      magnetic resonance (CMR) methods for discriminating acute from chronic myocardial
      infarction (MI). BACKGROUND: Although T2-weighted CMR is thought to be accurate
      in differentiating acute from chronic MI, few studies have reported on diagnostic
      accuracy, and these generally compared extremes in infarct age (e.g., <1 week old
      vs. more than 6 months old) and did not evaluate other CMR methods that could be
      informative. METHODS: A total of 221 CMR studies were performed at various time
      points after ST-segment elevation myocardial infarction in 117 consecutive
      patients without a history of MI or revascularization enrolled prospectively at 2
      centers. Imaging markers of acute MI (<1 month) were T2 hyperintensity on double
      inversion recovery turbo spin echo (DIR-TSE) images, microvascular obstruction
      (MO) on delayed-enhancement CMR, and focally increased end-diastolic wall
      thickness (EDWT) on cine-CMR. RESULTS: The prevalence of T2-DIR-TSE
      hyperintensity decreased with infarct age but remained substantial up to 6 months
      post-MI. In contrast, the prevalence of both MO and increased EDWT dropped
      sharply after 1 month. T2-DIR-TSE sensitivity, specificity, and accuracy for
      identifying acute MI were 88%, 66%, and 77% compared with 73%, 97%, and 85%,
      respectively, for the combination of MO or increased EDWT. On multivariable
      analysis, persistence of T2-hyperintensity in intermediate-age infarcts (1 to 6
      months old) was predicted by larger infarct size, diabetes, and better T2-DIR-TSE
      image quality score. For infarct size >= 10% of the left ventricle, a simple
      algorithm incorporating all CMR components allowed classification of infarct age
      into 3 categories (<1 month old, 1 to 6 months old, and >= 6 months old) with 80%
      (95% confidence interval: 73% to 87%) accuracy. CONCLUSIONS: T2-DIR-TSE
      hyperintensity is specific for infarcts <6 months old, whereas MO and increased
      EDWT are specific for infarcts <1 month old. Incorporating multiple CMR markers
      of acute MI and their varied longevity leads to a more precise assessment of
      infarct age.

PMID- 25981508
TI  - Right Heart Score for Predicting Outcome in Idiopathic, Familial, or Drug- and
      Toxin-Associated Pulmonary Arterial Hypertension.
AB  - OBJECTIVES: This study sought to determine whether a simple score combining
      indexes of right ventricular (RV) function and right atrial (RA) size would offer
      good discrimination of outcome in patients with pulmonary arterial hypertension
      (PAH). BACKGROUND: Identifying a simple score of outcome could simplify risk
      stratification of patients with PAH and potentially lead to improved tailored
      monitoring or therapy. METHODS: We recruited patients from both Stanford
      University (derivation cohort) and VU University Medical Center (validation
      cohort). The composite endpoint for the study was death or lung transplantation.
      A Cox proportional hazard with bootstrap CI adjustment model was used to
      determine independent correlates of death or transplantation. A predictive score
      was developed using the beta coefficients of the multivariable models. RESULTS:
      For the derivation cohort (n = 95), the majority of patients were female (79%),
      average age was 43 +/- 11 years, mean pulmonary arterial pressure was 54 +/- 14
      mm Hg, and pulmonary vascular resistance index was 25 +/- 12 Wood units * m(2).
      Over an average follow-up of 5 years, the composite endpoint occurred in 34
      patients, including 26 deaths and 8 patients requiring lung transplant. On
      multivariable analysis, RV systolic dysfunction grade (hazard ratio [HR]: 3.4 per
      grade; 95% confidence interval [CI]: 2.0 to 7.8; p < 0.001), severe RA
      enlargement (HR: 3.0; 95% CI: 1.3 to 8.1; p = 0.009), and systemic blood pressure
      <110 mm Hg (HR: 3.3; 95% CI: 1.5 to 9.4; p < 0.001) were independently associated
      with outcome. A right heart (RH) score constructed on the basis of these 3
      parameters compared favorably with the National Institutes of Health survival
      equation (0.88; 95% CI: 0.79 to 0.94 vs. 0.60; 95% CI: 0.49 to 0.71; p < 0.001)
      but was not statistically different than the REVEAL (Registry to Evaluate Early
      and Long-Term PAH Disease Management) score c-statistic of 0.80 (95% CI: 0.69 to
      0.88) with p = 0.097. In the validation cohort (n = 87), the RH score remained
      the strongest independent correlate of outcome. CONCLUSIONS: In patients with
      prevalent PAH, a simple RH score may offer good discrimination of long-term
      outcome.

PMID- 25981511
TI  - Geological Disposal of Radioactive Waste: A Long-Term Socio-Technical Experiment.
AB  - In this article we investigate whether long-term radioactive waste management by
      means of geological disposal can be understood as a social experiment. Geological
      disposal is a rather particular technology in the way it deals with the
      analytical and ethical complexities implied by the idea of technological
      innovation as social experimentation, because it is presented as a technology
      that ultimately functions without human involvement. We argue that, even when the
      long term function of the 'social' is foreseen to be restricted to safeguarding
      the functioning of the 'technical', geological disposal is still a social
      experiment. In order to better understand this argument and explore how it could
      be addressed, we elaborate the idea of social experimentation with the notion of
      co-production and the analytical tools of delegation, prescription and network as
      developed by actor-network theory. In doing so we emphasize that geological
      disposal inherently involves relations between surface and subsurface, between
      humans and nonhumans, between the social, material and natural realm, and that
      these relations require recognition and further elaboration. In other words, we
      argue that geological disposal concurrently is a social and a technical
      experiment, or better, a long-term socio-technical experiment. We end with
      proposing the idea of 'actor-networking' as a sensitizing concept for future
      research into what geological disposal as a socio-technical experiment could look
      like.

PMID- 25981509
TI  - The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with
      Lymphoma Depends on the Histological Subtype and the Intensity of the
      Conditioning Regimen.
AB  - The purpose of this study was to analyze the impact of graft-versus-host disease
      (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic
      hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of
      Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL),
      peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA
      identical sibling or unrelated donor hematopoietic cell transplantation between
      1997 and 2009 were included. Two thousand six hundred eleven cases were included.
      A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the
      transplantations. In a multivariate analysis of myeloablative cases (n = 970),
      neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with
      a lower incidence of relapse/progression in any lymphoma subtype. In contrast,
      the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a
      lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and
      in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and
      cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019,
      respectively). Of interest, the effect of GVHD on decreasing relapse was similar
      in patients with sensitive disease and chemoresistant disease. Unfortunately,
      both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and
      overall survival (OS) in FL cases but did not affect treatment-related mortality,
      OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for
      immunotherapy in FL and MCL patients.

PMID- 25981510
TI  - Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2
      Deletion Syndrome Family Trios for Genotype to Phenotype Correlations.
AB  - The 22q11.2 deletion syndrome (22q11DS) affects 1:4,000 live births and presents
      with highly variable phenotype expressivity. In this study, we developed an
      analytical approach utilizing whole-genome sequencing (WGS) and integrative
      analysis to discover genetic modifiers. Our pipeline combined available tools in
      order to prioritize rare, predicted deleterious, coding and noncoding single
      nucleotide variants (SNVs), and insertion/deletions from WGS. We sequenced two
      unrelated probands with 22q11DS, with contrasting clinical findings, and their
      unaffected parents. Proband P1 had cognitive impairment, psychotic episodes,
      anxiety, and tetralogy of Fallot (TOF), whereas proband P2 had juvenile
      rheumatoid arthritis but no other major clinical findings. In P1, we identified
      common variants in COMT and PRODH on 22q11.2 as well as rare potentially
      deleterious DNA variants in other behavioral/neurocognitive genes. We also
      identified a de novo SNV in ADNP2 (NM_014913.3:c.2243G>C), encoding a
      neuroprotective protein that may be involved in behavioral disorders. In P2, we
      identified a novel nonsynonymous SNV in ZFPM2 (NM_012082.3:c.1576C>T), a known
      causative gene for TOF, which may act as a protective variant downstream of TBX1,
      haploinsufficiency of which is responsible for congenital heart disease in
      individuals with 22q11DS. 

PMID- 25981507
TI  - Ethnic-Specific Normative Reference Values for Echocardiographic LA and LV Size,
      LV Mass, and Systolic Function: The EchoNoRMAL Study.
AB  - OBJECTIVES: This study sought to derive age-, sex-, and ethnic-appropriate adult
      reference values for left atrial (LA) and left ventricular (LV) dimensions and
      volumes, LV mass, fractional shortening, and ejection fraction (EF) derived from
      geographically diverse population studies. BACKGROUND: The current recommended
      reference values for measurements from echocardiography may not be suitable to
      the diverse world population to which they are now applied. METHODS: Population
      based datasets of echocardiographic measurements from 22,404 adults without
      clinical cardiovascular or renal disease, hypertension, or diabetes were combined
      in an individual person data meta-analysis. Quantile regression was used to
      derive reference values at the 95th percentile (upper reference value [URV]) and
      fifth percentile (lower reference value [LRV]) of each measurement against age
      (treated as linear), separately within sex and ethnic groups. RESULTS: The URVs
      for left ventricular end-diastolic volume (LVEDV), LV end-systolic volume, and LV
      stroke volume (SV) were highest in Europeans and lowest in South Asians.
      Important sex and ethnic differences remained after indexation by body surface
      area or height for these measurements, as well as for the LRV for SV. LVEDV and
      SV decreased with increasing age for all groups. Importantly, the LRV for EF
      differed by ethnicity; there was a clear apparent difference between Europeans
      and Asians. The URVs for LV end-diastolic diameter and LV end-systolic diameter
      were higher for Europeans than those for East Asian, South Asian, and African
      people, particularly among men. Similarly, the URVs for LA diameter and volume
      were highest for Europeans. CONCLUSIONS: Sex- and/or ethnic-appropriate
      echocardiographic reference values are indicated for many measurements of LA and
      LV size, LV mass, and EF. Reference values for LV volumes and mass also differ
      across the age range.

PMID- 25981512
TI  - Borderline pulmonary pressures in scleroderma - a 'pre-pulmonary arterial
      hypertension' condition?
AB  - Patients with systemic sclerosis may develop borderline pulmonary arterial
      pressure. The clinical relevance of this condition is not always clear. Reported
      data support the evidence that this subgroup may represent an intermediate stage
      between normal pulmonary arterial pressure and manifest pulmonary arterial
      hypertension, a serious complication in scleroderma. Recognizing the clinical
      relevance of borderline pulmonary arterial pressure increase in scleroderma
      patients, future studies should aim for clear evidence for diagnostic and
      therapeutic algorithms for this population. 

PMID- 25981513
TI  - Birth preparedness and complication readiness among recently delivered women in
      chamwino district, central Tanzania: a cross sectional study.
AB  - BACKGROUND: Unacceptably high maternal mortality rates remain a challenge in
      developing countries such as Tanzania. Birth Preparedness and Complication
      Readiness is among the key interventions that can reduce maternal mortality.
      Despite this, its status in Tanzania is not well documented. We assessed the
      practice and determinants of Birth preparedness and complication readiness among
      recently delivered women in Chamwino district, Central Tanzania. METHODS: A
      community based cross-sectional study was conducted to women who delivered two
      years prior to survey in January 2014 at Chamwino district, Tanzania. Woman was
      considered as prepared for birth and its complication if she reported at least
      three of these; know expected date of delivery, saved money, identified a skilled
      birth attendant/health facility, mode of transport and Identified two compatible
      blood donors. Descriptive, bivariate and multivariable logistic regression
      analyses were performed at P value < 0.05 level of significance. RESULTS: We
      interviewed 428 women whose median age (IQR) was 26.5 (22-33) years. About 249
      (58.2 %) of the respondents were considered as prepared for birth and its
      complications. After controlling for confounding and clustering effect,
      significant determinants of birth preparedness and complication readiness were
      found to be maternal education (AOR = 2.26, 95 % CI; 1.39, 3.67), spouse
      employment (AOR = 2.18, 95 % CI; 1.46, 3.25), booking at ANC (AOR = 2.03, 95 %
      CI; 1.11, 3.72), Four or more antenatal visits, (AOR = 1.94, 95 % CI; 1.17, 3.21)
      and knowledge of key danger signs (AOR = 4.16, 95 % CI; 2.32, 7.45). Prepared for
      birth was found to be associated with institutional delivery (AOR = 2.45, 95 %
      CI; 1.12, 5.34). CONCLUSION: The proportion of women who prepared for birth and
      its complications were found to be low. District reproductive and child health
      coordinator should emphasis on early and frequent antenatal care visits, since
      they were among predictors of birth preparedness and complication readiness.

PMID- 25981514
TI  - Donor-acceptor star-shaped conjugated macroelectrolytes: synthesis, light
      harvesting properties, and self-assembly-induced Forster resonance energy
      transfer.
AB  - A novel series of donor-acceptor star-shaped conjugated macroelectrolytes (CMEs),
      denoted as 4FTs, including anionic carboxylic acid sodium groups (4FNaT), neutral
      diethanolamine groups (4FNOHT), and cationic ammonium groups (4FNBrT), were
      designed, synthesized, and explored as an excellent platform to investigate the
      impact of various polar pendent groups on self-assembly behaviors. The resulting
      CMEs with donor-acceptor star-shaped architectures exhibited distinct light
      harvesting properties. The interactions between 4FTs and TrNBr, a star-shaped
      monodisperse CME grafted with cationic quaternary ammonium side chains, were
      investigated in H2O and CH3OH using steady-state, time-resolved fluorescence,
      dynamic light scattering (DLS), and transmission electron microscopy (TEM).
      Highly favored energy transfer has been proven by the excellent spectral overlap
      between TrNBr fluorescence and 4FTs absorptions which can be tuned by adjusting
      the pendent polar groups and solvents. It is suggested that self-assembled
      structures are formed between TrNBr and 4FNaT, while there is no obvious change
      for TrNBr/4FNOHT and TrNBr/4FNBrT in both H2O and CH3OH at low concentrations
      (<10(-6) M). This result is confirmed by the change of the TrNBr and 4FTs
      fluorescence properties and the time-resolved fluorescence data. The overall
      results manifest that at low concentrations the self-assembly between TrNBr and
      4FTs is dominated by the electrostatic interactions. This study suggests that the
      functionalization of pendent polar groups of star-shaped CMEs has proven to be
      effective to modulate the self-assembly behaviors in dilute solutions and thus
      provide a strategy to further manage the optoelectronic properties. 

PMID- 25981516
TI  - Primary sclerosing cholangitis: a clinical update.
AB  - INTRODUCTION: Primary sclerosing cholangitis (PSC) is a progressive cholestatic
      disorder that ultimately can lead to cirrhosis, liver failure, malignancy and
      death. It is strongly associated with inflammatory bowel disease (IBD), and
      though a rare disease, its incidence is increasing. There are no proven medical
      therapies for PSC. SOURCES OF DATA: Ovid Medline was utilised to search for
      articles with keywords 'sclerosing cholangitis' and 'cholangiocarcinoma' and
      containing titles 'primary sclerosing cholangitis', and references of these
      papers were cross-referenced for further relevant manuscripts. AREAS OF
      AGREEMENT: PSC is a rare disease, and there is a strong association with risk
      loci within the major histocompatibility complex and other genes common to other
      autoimmune diseases. PSC is a premalignant condition, associated with higher
      rates of hepatobiliary and colorectal cancer in patients with ulcerative colitis
      (UC). AREAS OF CONTROVERSY: The pathogenesis is unclear, and competing theories
      exist surrounding toxic bile acids, enhanced homing of particular T cells from
      the gut to the liver and increased passage of toxins to the liver through a
      permeable bowel wall. It is unclear whether the higher rate of colonic cancer in
      PSC/UC occurs in PSC/Crohn's disease. Ursodeoxycholic acid therapy reduces liver
      enzymes but has not been shown to improve survival. It may reduce the prevalence
      of bowel cancer. GROWING POINTS: Recent genetic studies have revealed new risk
      loci, pointing to the importance of the immune system and its interaction with
      the biome. AREAS TIMELY FOR DEVELOPING RESEARCH: On the basis of the genetic
      studies discussed earlier, novel agents are being developed and trialled in the
      treatment of PSC.

PMID- 25981515
TI  - Periostin: its role in asthma and its potential as a diagnostic or therapeutic
      target.
AB  - Accumulating evidence shows that periostin, a matricellular protein, is involved
      in many fundamental biological processes such as cell proliferation, cell
      invasion, and angiogenesis. Changes in periostin expression are commonly detected
      in various cancers and pre-cancerous conditions, and periostin may be involved in
      regulating a diverse set of cancer cell activities that contribute to
      tumorigenesis, cancer progression, and metastasis. Periostin has also been shown
      to be involved in many aspects of allergic inflammation, such as eosinophil
      recruitment, airway remodeling, development of a Th2 phenotype, and increased
      expression of inflammatory mediators. In an in vivo model, bronchoalveolar lavage
      (BAL) fluid obtained from ovalbumin-challenged mice was found to contain
      significantly higher levels of periostin compared to BAL samples from control
      mice. To date, the molecular mechanisms involving periostin in relation to asthma
      in humans have not been fully elucidated. This review will focus on what is known
      about periostin and its role in the pathophysiological mechanisms that mediate
      asthma in order to evaluate the potential for periostin to serve as a biomarker
      and therapeutic target for the detection and treatment of asthma, respectively. 

PMID- 25981517
TI  - Compounds Combining Aminoadamantane and Monoterpene Moieties: Cytotoxicity and
      Mutagenic Effects.
AB  - A series of secondary amines combining monoterpenoid and aminoadamantane moieties
      have been synthesized. Their cytotoxic activity against human cancer cells CEM
      13, MT-4, and U-937 has been studied for the first time. Most of the obtained
      compounds exhibited a significant cytotoxic activity with the median cytotoxic
      dose (CTD50) ranging from 6 to 84 uM. The most promising results were obtained
      for compound 2b which was synthesized from 1-aminoadamantane and (-)-myrtenal and
      revealed a high activity against all tumor lines used (CTD50 = 12 / 21 uM) along
      with low toxicity with respect to MDCK cells (CTD50 = 1500 uM). The synthesized
      amines do not exert the genotoxic effect on cells of the biosensor strain based
      on recombinant E. coli cells bearing the pRAC-gfp plasmid.

PMID- 25981518
TI  - alpha-Aminoisobutyric Acid Leads a Fluorescent syn-bimane LASER Probe Across the
      Blood-brain Barrier.
AB  - Penetration of the blood brain barrier (BBB) by appropriate fluorescent probes
      remains a challenge in optical imaging and diagnostics. We designed, synthesized
      and observed the in vivo BBB penetration of a LASER syn-bimane probe. Results
      demonstrate that the Aib transporter unit in our probe may lead a fluorescent
      bimanyl moiety across the BBB. 

PMID- 25981519
TI  - Prediction models need appropriate internal, internal-external, and external
      validation.

PMID- 25981520
TI  - A Ratiometric Sensor Using Single Chirality Near-Infrared Fluorescent Carbon
      Nanotubes: Application to In Vivo Monitoring.
AB  - Advances in the separation and functionalization of single walled carbon
      nanotubes (SWCNT) by their electronic type have enabled the development of
      ratiometric fluorescent SWCNT sensors for the first time. Herein, single
      chirality SWCNT are independently functionalized to recognize either nitric oxide
      (NO), hydrogen peroxide (H(2)O(2)), or no analyte (remaining invariant) to create
      optical sensor responses from the ratio of distinct emission peaks. This
      ratiometric approach provides a measure of analyte concentration, invariant to
      the absolute intensity emitted from the sensors and hence, more stable to
      external noise and detection geometry. Two distinct ratiometric sensors are
      demonstrated: one version for H(2)O(2), the other for NO, each using 7,6
      emission, and each containing an invariant 6,5 emission wavelength. To
      functionalize these sensors from SWCNT isolated from the gel separation
      technique, a method for rapid and efficient coating exchange of single chirality
      sodium dodecyl sulfate-SWCNT is introduced. As a proof of concept, spatial and
      temporal patterns of the ratio sensor response to H(2)O(2) and, separately, NO,
      are monitored in leaves of living plants in real time. This ratiometric optical
      sensing platform can enable the detection of trace analytes in complex
      environments such as strongly scattering media and biological tissues.

PMID- 25981521
TI  - Activity of the porcine gonadotropin-releasing hormone receptor gene promoter is
      partially conferred by a distal gonadotrope specific element (GSE) within an
      upstream enhancing region, two proximal GSEs and a retinoid X receptor binding
      site.
AB  - BACKGROUND: Regulation of gonadotropin-releasing hormone (GnRH) receptor (GnRHR)
      numbers on gonadotropes within the anterior pituitary gland represents a critical
      point for control of reproductive function. Binding of GnRH to its receptor
      regulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) release
      and levels of this G-protein coupled receptor on the surface of gonadotropes
      determines their sensitivity to GnRH pulses. While transcriptional regulation of
      this gene has been studied in mice, rats, humans and sheep, little is known about
      its regulation in the pig, an important agricultural species and human research
      model. METHODS: We isolated 5118 bp of 5' flanking sequence for the porcine GnRHR
      gene and generated luciferase reporter vectors. Deletion and mutation constructs
      were evaluated in gonadotrope-derived alphaT3-1 cells to determine regions
      important for gene transcription. Additionally, electrophoretic mobility shift
      assays (EMSAs) were performed to identify transcription factors binding to the
      GnRHR promoter. RESULTS: Transient transfections revealed that the GnRHR promoter
      was functional in alphaT3-1 cells but not in cells of non-gonadotrope origin.
      Mutation of the highly conserved gonadotrope specific element (GSE) located at 
      179/-171 of proximal promoter completely ablated luciferase activity, whereas
      mutation of another GSE at -315/-310 reduced activity by 34%. Consistent with
      this, EMSAs using alphaT3-1 nuclear extracts and a steroidogenic factor (SF)1
      antibody confirmed SF1 binding to both GSEs. EMSAs also demonstrated that a
      retinoid X receptor (RXR) binding site at -279/-274 binds RXRalpha and RXRbeta
      and mutation of this site eliminated promoter activity. Transient transfection of
      alphaT3-1 cells with reporter vectors containing selective removal of 5' flanking
      region for the porcine GnRHR gene indicated that the -1915/-1431 segment was
      important for promoter activity. Definition of this region via transfection
      assays and EMSAs revealed an upstream enhancing region located at -1779/-1667
      that increases porcine GnRHR gene expression in alphaT3-1 cells and includes a
      SF1 binding site at -1760/-1753. CONCLUSIONS: Porcine GnRHR promoter activity in
      alphaT3-1 cells is partially conferred by a distal GSE, two proximal GSEs and a
      RXR binding site. Basal gonadotrope expression of the porcine GnRHR gene uniquely
      involves three GSEs and RXR is newly identified as a regulator of GnRHR promoter
      activity.

PMID- 25981522
TI  - The coil orientation dependency of the electric field induced by TMS for M1 and
      other brain areas.
AB  - BACKGROUND: The effectiveness of transcranial magnetic stimulation (TMS) depends
      highly on the coil orientation relative to the subject's head. This implies that
      the direction of the induced electric field has a large effect on the efficiency
      of TMS. To improve future protocols, knowledge about the relationship between the
      coil orientation and the direction of the induced electric field on the one hand,
      and the head and brain anatomy on the other hand, seems crucial. Therefore, the
      induced electric field in the cortex as a function of the coil orientation has
      been examined in this study. METHODS: The effect of changing the coil orientation
      on the induced electric field was evaluated for fourteen cortical targets. We
      used a finite element model to calculate the induced electric fields for thirty
      six coil orientations (10 degrees resolution) per target location. The effects on
      the electric field due to coil rotation, in combination with target site anatomy,
      have been quantified. RESULTS: The results confirm that the electric field
      perpendicular to the anterior sulcal wall of the central sulcus is highly
      susceptible to coil orientation changes and has to be maximized for an optimal
      stimulation effect of the motor cortex. In order to obtain maximum stimulation
      effect in areas other than the motor cortex, the electric field perpendicular to
      the cortical surface in those areas has to be maximized as well. Small
      orientation changes (10 degrees) do not alter the induced electric field
      drastically. CONCLUSIONS: The results suggest that for all cortical targets,
      maximizing the strength of the electric field perpendicular to the targeted
      cortical surface area (and inward directed) optimizes the effect of TMS.
      Orienting the TMS coil based on anatomical information (anatomical magnetic
      resonance imaging data) about the targeted brain area can improve future results.
      The standard coil orientations, used in cognitive and clinical neuroscience,
      induce (near) optimal electric fields in the subject-specific head model in most
      cases.

PMID- 25981523
TI  - Association of chemical constituents and pollution sources of ambient fine
      particulate air pollution and biomarkers of oxidative stress associated with
      atherosclerosis: A panel study among young adults in Beijing, China.
AB  - Ambient particulate air pollution has been associated with increased oxidative
      stress and atherosclerosis, but the chemical constituents and pollution sources
      behind the association are unclear. We investigated the associations of various
      chemical constituents and pollution sources of ambient fine particles (PM2.5)
      with biomarkers of oxidative stress in a panel of 40 healthy university students.
      Study participants underwent repeated blood collections for 12 times before and
      after relocating from a suburban campus to an urban campus with high air
      pollution levels in Beijing, China. Air pollution data were obtained from central
      air-monitoring stations, and plasma levels of oxidized low-density lipoprotein
      (Ox-LDL) and soluble CD36 (sCD36) were determined in the laboratory (n=464).
      Linear mixed-effects models were used to estimate the changes in biomarkers in
      association with exposure variables. PM2.5 iron and nickel were positively
      associated with Ox-LDL (p<0.05). For each interquartile range increase in iron (1
      day, 0.51 MUg/m(3)) and nickel (2-day, 2.5 ng/m(3)), there were a 1.9% [95%
      confidence interval (CI): 0.2%, 3.7%] increase and a 1.8% (95% CI: 0.2%, 3.4%)
      increase in Ox-LDL, respectively. We also found that each interquartile range
      increase in calcium (1-day, 0.7 MUg/m(3)) was associated with a 4.8% (95% CI:
      0.7%, 9.1%) increase in sCD36. Among the pollution sources, PM2.5 from traffic
      emissions and coal combustion were suggestively and positively associated with Ox
      LDL. Our findings suggest that a subset of metals in airborne particles may be
      the major air pollution components that contribute to the increased oxidative
      stress associated with atherosclerosis.

PMID- 25981524
TI  - Different serotypes of dengue viruses differently regulate the expression of the
      host cell antigen processing machinery.
AB  - Dengue virus (DV) infection demonstrates an intriguing virus-induced
      intracellular membrane alteration that results in the augmentation of major
      histocompatibility complex (MHC) class I-restricted antigen presentation. As
      oppose to its biological function in attracting CD8(+) T-cells, this phenomenon
      appears to facilitate the immune evasion. However, the molecular events that
      attribute to the dysregulation of the antigen presenting mechanism (APM) by DV
      remain obscure. In this study, we aimed to characterize the host cell APM upon
      infection with all serotypes of whole DV. Cellular RNA were isolated from
      infected cells and the gene expressions of LMP2, LMP7, TAP1, TAP2, TAPBP, CALR,
      CANX, PDIA3, HLA-A and HLA-B were analyzed via quantitative PCR. The profiles of
      the gene expression were further validated. We showed that all four DV serotypes
      modulate host APM at the proteasomal level with DV2 showing the most prominent
      expression profile. 

PMID- 25981525
TI  - A prospective, active haemovigilance study with combined cohort analysis of
      19,175 transfusions of platelet components prepared with amotosalen-UVA
      photochemical treatment.
AB  - BACKGROUND AND OBJECTIVES: A photochemical treatment process (PCT) utilizing
      amotosalen and UVA light (INTERCEPT(TM) Blood System) has been developed for
      inactivation of viruses, bacteria, parasites and leucocytes that can contaminate
      blood components intended for transfusion. The objective of this study was to
      further characterize the safety profile of INTERCEPT-treated platelet components
      (PCT-PLT) administered across a broad patient population. MATERIALS AND METHODS:
      This open-label, observational haemovigilance programme of PCT-PLT transfusions
      was conducted in 21 centres in 11 countries. All transfusions were monitored for
      adverse events within 24 h post-transfusion and for serious adverse events (SAEs)
      up to 7 days post-transfusion. All adverse events were assessed for severity
      (Grade 0-4), and causal relationship to PCT-PLT transfusion. RESULTS: Over the
      course of 7 years in the study centres, 4067 patients received 19,175 PCT-PLT
      transfusions. Adverse events were infrequent, and most were of Grade 1 severity.
      On a per-transfusion basis, 123 (0.6%) were classified an acute transfusion
      reaction (ATR) defined as an adverse event related to the transfusion. Among
      these ATRs, the most common were chills (77, 0.4%) and urticaria (41, 0.2%).
      Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion
      (<0.1%). No case of transfusion-related acute lung injury, transfusion-associated
      graft-versus-host disease, transfusion-transmitted infection or death was
      attributed to the transfusion of PCT-PLT. CONCLUSION: This longitudinal
      haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a
      low rate of ATRs, and a safety profile consistent with that previously reported
      for conventional platelet components.

PMID- 25981526
TI  - Visual perceptions of male obesity: a cross-cultural study examining male and
      female lay perceptions of obesity in Caucasian males.
AB  - BACKGROUND: Obesity is now common and this may have altered visual perceptions of
      what constitutes a 'normal' and therefore healthy weight. The present study
      examined cross-cultural differences in male and female participants' ability to
      visually identify the weight status of photographed Caucasian males. METHODS:
      Five hundred and fifty three male and female young adults from the US (high
      obesity prevalence), UK and Sweden (lower obesity prevalence) participated in an
      online study. Participants judged the weight status of a series of photographed
      healthy weight, overweight and obese (class I) Caucasian males and rated the
      extent to which they believed each male should consider losing weight. RESULTS:
      There was a strong tendency for both male and female participants to
      underestimate the weight status of the photographed overweight and obese males.
      Photographed males were frequently perceived as being of healthier weight than
      they actually were. Some modest cross-cultural differences were also observed; US
      participants were worse at recognising obesity than UK participants (p < 0.05)
      and were also significantly more likely to believe that the photographed obese
      males did not need to consider losing weight, in comparison to both the UK and
      Swedish participants (ps < 0.05). No cross-cultural differences were observed for
      perceptions or attitudes towards the photographed healthy weight or overweight
      males. CONCLUSIONS: The weight status of overweight and obese (class I) Caucasian
      males is underestimated when judged by males and females using visual information
      alone. This study provides initial evidence of modest cross-cultural differences
      in attitudes toward, and the ability to recognise, obesity in Caucasian males.

PMID- 25981529
TI  - Editorial: Controversies and Current Approaches in the Diagnosis of Prediabetes
      and Diabetes Mellitus.

PMID- 25981528
TI  - Patients' perception of own efforts versus clinically observed outcomes of non
      surgical periodontal therapy in a Norwegian population: an observational study.
AB  - BACKGROUND: Most periodontal intervention studies have focused on biomedical
      qualities like change in pocket depth and clinical attachment levels. Very few
      studies have described patient response in terms of how patients' general lives
      are affected by disease, treatment, and communication with therapy providers.
      Thus the aim of the present study was to investigate patient response to
      systematic periodontal information, motivation and treatment strategy (primary
      aim) by comparing the patients' perception of own efforts and results with those
      clinically registered in a trans-sectional, observational study (secondary aim).
      METHODS: One year after treatment of 184 patients, 152 completed a questionnaire
      covering aspects of received oral health information and instruction,
      expectations, communication with the therapeutic team, behavioral change, self
      perceived outcomes and satisfaction. RESULTS: More than 90% of the patients were
      satisfied with the interaction with the specialist team. 98% were satisfied with
      the information and instruction they had been given. 84% said that the
      information had been necessary to make them change their behavior towards better
      oral hygiene. Pain and discomfort, as well as bleeding were reduced substantially
      from before to after treatment, and 28 patients reported to have stopped smoking.
      In all questions regarding well-being there were statistically significant
      changes towards positive impact following therapy. CONCLUSIONS: Periodontal
      treatment, including customized information and education on the etiology and
      pathogenesis, prevention and treatment as well as maintenance of periodontal
      diseases resulted in a high degree of short- and long term compliance, and very
      good patient centered outcomes, which again had a positive impact on the
      patients' satisfaction. The patient centered outcomes correlated mostly with the
      compared clinical endpoints. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01318928.

PMID- 25981527
TI  - CGGBP1 mitigates cytosine methylation at repetitive DNA sequences.
AB  - BACKGROUND: CGGBP1 is a repetitive DNA-binding transcription regulator with
      target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1
      LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however
      remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism
      of transcriptional repression. Concordantly, gene-rich regions typically carry
      lower levels of CpG methylation than the repetitive elements. It is well known
      that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG
      methylation constitute a transcriptional silencing and retrotransposon
      inactivating mechanism. RESULTS: Here, we have studied genome-wide CpG
      methylation with or without CGGBP1-depletion. By high throughput sequencing of
      bisulfite-treated genomic DNA we have identified CGGBP1 to be a negative
      regulator of CpG methylation at repetitive DNA sequences. In addition, we have
      studied CpG methylation alterations on Alu and L1 retrotransposons in CGGBP1
      depleted cells using a novel bisulfite-treatment and high throughput sequencing
      approach. CONCLUSIONS: The results clearly show that CGGBP1 is a possible
      bidirectional regulator of CpG methylation at Alus, and acts as a repressor of
      methylation at L1 retrotransposons.

PMID- 25981530
TI  - Oxidant/antioxidant effects of chronic exposure to predator odor in prefrontal
      cortex, amygdala, and hypothalamus.
AB  - The incidence of anxiety-related diseases is increasing these days, hence there
      is a need to understand the mechanisms that underlie its nature and consequences.
      It is known that limbic structures, mainly the prefrontal cortex and amygdala,
      are involved in the processing of anxiety, and that projections from prefrontal
      cortex and amygdala can induce activity of the hypothalamic-pituitary-adrenal
      axis with consequent cardiovascular changes, increase in oxygen consumption, and
      ROS production. The compensatory reaction can include increased antioxidant
      enzymes activities, overexpression of antioxidant enzymes, and genetic shifts
      that could include the activation of antioxidant genes. The main objective of
      this study was to evaluate the oxidant/antioxidant effect that chronic anxiogenic
      stress exposure can have in prefrontal cortex, amygdala, and hypothalamus by
      exposition to predator odor. Results showed (a) sensitization of the HPA axis
      response, (b) an enzymatic phase 1 and 2 antioxidant response to oxidative stress
      in amygdala, (c) an antioxidant stability without elevation of oxidative markers
      in prefrontal cortex, (d) an elevation in phase 1 antioxidant response in
      hypothalamus. Chronic exposure to predator odor has an impact in the metabolic
      REDOX state in amygdala, prefrontal cortex, and hypothalamus, with oxidative
      stress being prevalent in amygdala as this is the principal structure responsible
      for the management of anxiety. 

PMID- 25981531
TI  - The AKT signaling pathway sustains the osteogenic differentiation in human dental
      follicle cells.
AB  - Signaling transduction pathways are established by interactions between growth
      factors, protein kinases, and transcription factors, and they play a crucial role
      in tooth development. Precursor cells of the dental follicle (DFCs) are used for
      in vitro studies about molecular mechanisms during periodontal development.
      Previous studies have already shown that the growth factor BMP2 and the
      transcription factor EGR1 are involved in the osteogenic differentiation in DFCs
      while interactions with protein kinase-based pathways remain elusive. In this
      current study, we investigated the role of the AKT kinase signaling pathway for
      the osteogenic differentiation in DFCs. The AKT signaling pathway was activated
      in DFCs after the induction of the osteogenic differentiation by BMP2. The
      inhibition of AKT in DFCs repressed the differentiation and the expression of the
      transcription factor EGR1. Interestingly, EGR1 bound to the phosphorylated form
      of SMAD1/5 (pSMAD). The binding of pSMAD to EGR1 was increased after the
      induction with BMP2. Moreover, the overexpression EGR1 increased the osteogenic
      differentiation of DFCs. Our results suggest that the AKT signaling pathway
      submits the BMP2-dependent osteogenic differentiation in DFCs via the expression
      of the transcription factor EGR1. 

PMID- 25981532
TI  - Evidence for inhibition of nitric oxide and inducible nitric oxide synthase in
      Caco-2 and RAW 264.7 cells by a Maillard reaction product [5-(5,6-dihydro-4H
      pyridin-3-ylidenemethyl)furan-2-yl]-methanol.
AB  - We have recently isolated and characterized the chemical structure of a bioactive
      Maillard reaction product, [5-(5,6-dihydro-4H-pyridin-3-ylidenemethyl)furan-2-yl]
      methanol (F3-A), from an aqueous glucose (Glc) and lysine (Lys) Maillard reaction
      (MR) model system. Here, we investigate further the mechanisms for anti
      inflammatory effects of this product in Caco-2 and RAW 264.7 cells. The anti
      inflammatory capacity of F3-A recovered from Glc-Lys MR mixture and a synthesized
      product were compared with those of the specific inducible nitric oxide synthase
      (iNOS) inhibitor, aminoguanidine (AG), and the nuclear factor-kappa B (NF-kappaB)
      inhibitor, pyrrolidine dithiocarbamate (PDTC). F3-A produced a dose-dependent
      inhibition of extracellular nitric oxide (NO) production and iNOS translation in
      Caco-2 cells induced with interferon gamma (IFN-gamma) and phorbol 12-myristate
      13-acetate (PMA), and these effects were more potent than those obtained with AG.
      Moreover, a combination of F3-A and AG to attenuate intestinal inflammation was
      additive. However, F3-A inhibited only intracellular NO production in RAW 264.7
      cells and did not inhibit COX-2 or NF-kappaB in either cell line. We conclude
      that the anti-inflammatory properties of F3-A are cell specific, working through
      different mechanism between macrophages and intestinal cells. 

PMID- 25981534
TI  - Effects of metalloprotease anthrax lethal factor on its peptide-based inhibitor
      R9LF-1.
AB  - The metalloprotease lethal factor (LF) from Bacillus anthracis plays a vital role
      in anthrax toxin action, and thus becomes a target for anti-anthrax therapy.
      Following the guidelines based on existing metalloprotease inhibitors, we
      designed a 'first-generation' LF inhibitor R9LF-1. This inhibitor was shown to be
      very stable by itself in a wide range of pH and temperature and able to inhibit
      LF activity in vitro. However, as we reported previously in the presence of LF,
      this inhibitor was degraded to a small molecular weight species, resulting in a
      significantly decreased ability to protect MAPKK from cleavage by LF as well as
      to protect murine macrophages from lethal toxin. In order to elucidate this
      unusual phenomenon to build solid basis for high-efficiency LF inhibitor
      development, we performed extensive research to study the effect of LF on its
      peptide-based inhibitor. Effects of temperature and incubation period of time on
      generation of the smaller peptide (short version R9LF-1) by LF as well as its
      catalytic domain were analyzed. We found that LF degraded R9LF-1 with maximum
      efficiency in the pH range of 7.0-8.5, which correlates well with the range of LF
      enzymatic activity with its native substrate. The degradation showed a deviation
      from normal hyperbolic kinetics but a similarity to the kinetics profile of an
      enzyme-catalyzed reaction with positive cooperativity. The short version R9LF-1
      had decreased inhibitory activity toward LF; surprisingly, BIAcore results
      suggested a better affinity for its binding to LF. In addition, R9LF-1 was not
      hydrolyzed by other common proteases, such as chymotrypsin and pepsin, suggesting
      hydrolysis of the bond between amino acid and hydroxamate groups is unique to LF.
      This study calls for caution when designing peptide-based LF inhibitors and when
      interpreting effects of these types of inhibitors. 

PMID- 25981533
TI  - Phylogeny and expression pattern of starch branching enzyme family genes in
      cassava (Manihot esculenta Crantz) under diverse environments.
AB  - Starch branching enzyme (SBE) is one of the key enzymes involved in starch
      biosynthetic metabolism. In this study, six SBE family genes were identified from
      the cassava genome. Phylogenetic analysis divided the MeSBE family genes into
      dicot family A, B, C, and the new group. Tissue-specific analysis showed that
      MeSBE2.2 was strongly expressed in leaves, stems cortex, and root stele, and
      MeSBE3 had high expression levels in stem cortex and root stele of plants in the
      rapid growth stage under field condition, whereas the expression levels of
      MeSBE2.1, MeSBE4, and MeSBE5 were low except for in stems cortex. The
      transcriptional activity of MeSBE2.2 and MeSBE3 was higher compared with other
      members and gradually increased in the storage roots during root growth process,
      while the other MeSBE members normally remained low expression levels. Expression
      of MeSBE2.2 could be induced by salt, drought, exogenous abscisic acid, jasmonic
      acid, and salicylic acid signals, while MeSBE3 had positive response to drought,
      salt, exogenous abscisic acid, and salicylic acid in leaves but not in storage
      root, indicating that they might be more important in starch biosynthesis pathway
      under diverse environments. 

PMID- 25981535
TI  - Intracellular angiotensin (1-7) increases the inward calcium current in
      cardiomyocytes. On the role of PKA activation.
AB  - The influence of intracellular administration of angiotensin (1-7) (Ang 1-7) on
      the inward calcium current was investigated in myocytes isolated from the left
      ventricle of Wistar Kyoto rat hearts using the patch-clamp technique. The results
      indicated: (1) the intracellular administration of Ang (1-7) (100 nM) enhanced
      the peak inward calcium current (I Ca); (2) the intracellular administration of
      A779 (100 nM) which a Mas receptor inhibitor, abolished the effect of Ang (1-7)
      on the calcium current; (3) the activation of PKA and consequent phosphorylation
      of calcium channels seems to be the mechanism involved in the increment of
      calcium current induced by the heptapeptide because the intracellular dialysis of
      the PKA inhibitor suppressed the effect of the heptapeptide; (4) the effect of
      Ang (1-7) was not related to its secretion into the extracellular space;
      (5)intracellular dialysis of Ang II (100 nM) has an opposite effect and reduced
      the peak I Ca; (6) extracellular administration of Ang II (100 nM) to cells
      previously dialyzed with Ang (1-7) also reduced the peak I Ca previously enhanced
      by Ang (1-7); and (7) intracellular Ang (1-7) reduced the heart cell volume.
      Implications for heart contractility were discussed. 

PMID- 25981536
TI  - Functions of miR-1 and miR-133a during the postnatal development of masseter and
      gastrocnemius muscles.
AB  - The present study investigated the function of miR-1 and miR-133a during the
      postnatal development of mouse skeletal muscles. The amounts of miR-1 and miR
      133a were measured in mouse masseter and gastrocnemius muscles between 1 and 12
      weeks after birth with real-time polymerase chain reaction and those of HDACs,
      MEF2, MyoD family, MCK, SRF, and Cyclin D1 were measured at 2 and 12 weeks with
      Western blotting. In both the masseter and gastrocnemius muscles, the amount of
      miR-1 increased between 1 and 12 weeks, whereas the amount of HADC4 decreased
      between 2 and 12 weeks. In the masseter muscle, those of MEF2, MyoD, Myogenin,
      and MCK increased between 2 and 12 weeks, whereas, in the gastrocnemius muscle,
      only those of MRF4 and MCK increased. The extent of these changes in the masseter
      muscle was greater than that in the gastrocnemius muscle. The amounts of miR
      133a, SRF, and Cyclin D1 did not change significantly in the masseter muscle
      between 1 and 12 weeks after birth. By contrast, in the gastrocnemius muscle, the
      amounts of miR-133a and Cyclin D1 increased, whereas that of SRF decreased. Our
      findings suggest that the regulatory pathway of miR-1 via HDAC4 and MEF2 plays a
      more prominent role during postnatal development in the masseter muscle than in
      the gastrocnemius muscle, whereas that of miR-133a via SRF plays a more prominent
      role in the gastrocnemius muscle than in the masseter muscle. 

PMID- 25981537
TI  - Involvement of PRIP (Phospholipase C-Related But Catalytically Inactive Protein)
      in BMP-Induced Smad Signaling in Osteoblast Differentiation.
AB  - Phospholipase C-related but catalytically inactive protein (PRIP) was first
      isolated as an inositol 1,4,5-trisphosphate binding protein. We generated PRIP
      gene-deficient mice which exhibited the increased bone mineral density and
      trabecular bone volume, indicating that PRIP is implicated in the regulation of
      bone properties. In this study, we investigated the possible mechanisms by which
      PRIP plays a role in bone morphogenetic protein (BMP) signaling, by analyzing the
      culture of primary cells isolated from calvaria of two genotypes, the wild type
      and a mutant. In the mutant culture, enhanced osteoblast differentiation was
      observed by measuring alkaline phosphatase staining and activity. The promoter
      activity of Id1 gene, responding immediately to BMP, was also more increased.
      Smad1/5 phosphorylation in response to BMP showed an enhanced peak and was more
      persistent in mutant cells, but the dephosphorylation process was not different
      between the two genotypes. The luciferase assay using calvaria cells transfected
      with the Smad1 mutated as a constitutive active form showed increased
      transcriptional activity at similar levels between the genotypes. The expression
      of BMP receptors was not different between the genotypes. BMP-induced
      phosphorylation of Smad1/5 was robustly decreased in wild type cells, but not in
      mutant cells, by pretreatment with DB867, an inhibitor of methyltransferase of
      inhibitory Smad6. Furthermore, BMP-induced translocation of Smad6 from nucleus to
      cytosol was not much observed in PRIP-deficient cells. These results indicate
      that PRIP is implicated in BMP-induced osteoblast differentiation by the negative
      regulation of Smad phosphorylation, through the methylation of inhibitory Smad6.

PMID- 25981538
TI  - Effects of plant antimicrobial phenolic compounds on virulence of the genus
      Pectobacterium.
AB  - Pectobacterium spp. are among the most devastating necrotrophs, attacking more
      than 50% of angiosperm plant orders. Their virulence strategy is based mainly on
      the secretion of exoenzymes that degrade the cell walls of their hosts, providing
      nutrients to the bacteria, but conversely, exposing the bacteria to plant defense
      compounds. In the present study, we screened plant-derived antimicrobial
      compounds, mainly phenolic acids and polyphenols, for their ability to affect
      virulence determinants including motility, biofilm formation and extracellular
      enzyme activities of different Pectobacteria: Pectobacterium carotovorum, P.
      brasiliensis, P. atrosepticum and P. aroidearum. In addition, virulence assays
      were performed on three different plant hosts following exposure of the bacteria
      to selected phenolic compounds. These experiments showed that cinnamic, coumaric,
      syringic and salicylic acids and catechol can considerably reduce disease
      severity, ranging from 20 to 100%. The reduced disease severity was not only the
      result of reduced bacterial growth, but also of a direct effect of the compounds
      on important bacterial virulence determinants, including pectolytic and
      proteolytic exoenzyme activities, that were reduced by 50-100%. This is the first
      report revealing a direct effect of phenolic compounds on virulence factors in a
      wide range of Pectobacterium strains. 

PMID- 25981540
TI  - Structural characterization of flavonoid C- and O-glycosides in an extract of
      Adhatoda vasica leaves by liquid chromatography with quadrupole time-of-flight
      mass spectrometry.
AB  - RATIONALE: Adhatoda vasica Nees is a well-known Ayurvedic medicinal plant,
      belonging to the family Acanthaceae. This study aims to seek identification and
      characterization of flavonoid C- and O-glycosides in the aqueous fraction of the
      plant leaves. METHODS: A method was developed for simultaneous characterization
      of flavonoids and their glycosides using high-pressure liquid chromatography with
      quadrupole time-of-flight mass spectrometry (HPLC/ESI-QTOF-MS/MS). The
      chromatographic separation was carried on an Agilent Poroshell 120 EC-C18 column
      (4.6 * 150 mm, 2.7 um) operated with 0.1% formic acid aqueous solution and
      methanol as the mobile phase. RESULTS: The fragmentations of the studied [M-H](-)
      ions of C-glycosides were shown to be cross-ring cleavages of the glycoside
      moiety [M-H-(60/90/120)](-) whereas O-glycosides were shown to eliminate the
      sugar moiety (Y0 (-) or [Y0 -H](-) ) from the aglycone unit; 6-C-glycosides
      exhibited [M-H-18](-) , a characteristic ion, and also a higher abundance of
      (0,3) X6 or 8 ions in comparison to 8-C glycosides; flavonoid 6,8-di-C-glycosides
      exhibited cross-ring cleavages of the sugar attached to the C-6 position
      preferentially. CONCLUSIONS: This method was successfully applied for analysis of
      flavonoids and their glycosides in Adhatoda vasica leaves. A total of 29
      compounds were tentatively identified including 17 C-, nine O-glycosides and
      three flavonoids.

PMID- 25981539
TI  - The effect of lysophosphatidic acid during in vitro maturation of bovine cumulus
      oocyte complexes: cumulus expansion, glucose metabolism and expression of genes
      involved in the ovulatory cascade, oocyte and blastocyst competence.
AB  - BACKGROUND: In the cow, lysophosphatidic acid (LPA) acts as an auto-/paracrine
      factor, through its receptors LPAR1-4, on oocytes and cumulus cells during in
      vitro maturation (IVM). The aim of the present work was to determine the effect
      of LPA during IVM of bovine oocytes on: 1) oocyte maturation; 2) apoptosis of
      COCs; 3) expression of genes involved in developmental competence and apoptosis
      in bovine oocytes and subsequent blastocysts; 4) cumulus expansion and expression
      of genes involved in the ovulatory cascade in cumulus cells; 5) glucose
      metabolism and expression of genes involved in glucose utilization in cumulus
      cells; 6) cleavage and blastocyst rates on Day 2 and Day 7 of in vitro culture,
      respectively. METHODS: Cumulus-oocyte complexes (COCs) were matured in vitro in
      the presence or absence of LPA (10(-5) M) for 24 h. Following maturation, we
      determined: oocyte maturation stage, cumulus expansion, COCs apoptosis and
      glucose and lactate levels in the maturation medium. Moreover, COCs were either
      used for gene expression analysis or fertilized in vitro. The embryos were
      cultured until Day 7 to assess cleavage and blastocyst rates. Oocytes, cumulus
      cells and blastocysts were used for gene expression analysis. RESULTS:
      Supplementation of the maturation medium with LPA enhanced oocyte maturation
      rates and stimulated the expression of developmental competence-related factors
      (OCT4, SOX2, IGF2R) in oocytes and subsequent blastocysts. Moreover, LPA reduced
      the occurrence of apoptosis in COCs and promoted an antiapoptotic balance in the
      transcription of genes involved in apoptosis (BAX and BCL2) either in oocytes or
      blastocysts. LPA increased glucose uptake by COCs via augmentation of GLUT1
      expression in cumulus cells as well as stimulating lactate production via the
      enhancement of PFKP expression in cumulus cells. LPA did not affect cumulus
      expansion as visually assessed, however, it stimulated upstream genes of cumulus
      expansion cascade, AREG and EREG. CONCLUSIONS: Supplementation of the maturation
      medium with LPA improves oocyte maturation rates, decreases extent of apoptosis
      in COCs and sustains the expression of developmental competence related factors
      during oocyte maturation and subsequently affects gene expression profile at the
      blastocyst stage. We also demonstrate that LPA directs glucose metabolism toward
      the glycolytic pathway during IVM.

PMID- 25981541
TI  - Determining the suitability of mass spectrometry for understanding the
      dissolution processes involved with pharmaceutical tablets.
AB  - RATIONALE: A current challenge for analytical chemists is the development of the
      measurement systems and approaches required to understand dynamic processes such
      as tablet dissolution. The design and development of oral tablets could be
      improved by the availability of detailed information about the rates of release
      of the individual tablet components. Small footprint mass spectrometry (MS)
      systems are gaining use for on-line reaction monitoring because of their ability
      to rapidly determine multiple reactant, intermediate, and product species. We
      have therefore assessed the utility of such MS systems to the study of
      dissolution processes. METHODS: Aqueous dissolution media containing phosphate
      and other non-volatile buffer salts were pumped from a standard USPII dissolution
      vessel through an active splitter and back. The splitter sampled the dissolution
      stream and diluted it into a make-up flow which was pumped to a small single
      quadrupole mass spectrometer. Single ion monitoring was used to quantify the ions
      of interest. Three different bio-relevant dissolution media were studied to gauge
      the effect of the sample matrix. RESULTS: Individual dissolution profiles were
      obtained from a tablet containing three drugs, and lactose as the soluble filler.
      This was successfully demonstrated with three different bio-relevant media
      designed to reflect the pH of the different sections of the human gastro
      intestinal tract. Component concentrations as low as 0.06 ug/mL (representing 1%
      dissolution) were detected. The MS dissolution profiles correlated with the
      visual observation of tablet dissolution. MS gave linear responses with
      concentration for the individual components, although analysis of the tablet
      solution indicated that ion suppression is an area for further investigation.
      CONCLUSIONS: An on-line MS system was used to determine the individual
      dissolution profiles of three drugs and lactose as they were released from the
      same tablet. The level of each of these components in solution was determined
      every 10 seconds, and each had a similar release profile. The dissolution
      profiles were determined using inorganic buffer solutions at three different bio
      relevant pHs.

PMID- 25981543
TI  - Matrix-assisted laser desorption/ionisation quadrupole ion trap time-of-flight
      mass spectrometry of novel shape-persistent macrocycles.
AB  - RATIONALE: Shape-persistent macrocycles (SPMs) represent innovative molecular
      building blocks for the development of highly organised supramolecular
      architectures with application in nanotechnology, chemistry, catalysis and
      optoelectronics. Systematic mass spectrometric characterisation of SPMs and their
      collision-activated decay is not available to date. METHODS: Characterisation of
      alkoxy-decorated SPMs was performed by matrix-assisted laser
      desorption/ionisation quadrupole ion trap time-of-flight mass spectrometry (MALDI
      QIT-TOFMS) and collision-induced dissociation (CID). RESULTS: Laser excitation of
      SPMs leads to the formation of stable cation radicals which show characteristic
      fragmentation patterns. All the product ions formed were identified.
      Photoelectrons generated during the MALDI process and full-ring conjugation were
      found to be fundamental for the formation of molecular cation radicals and their
      stabilisation, respectively. Formation of supramolecular aggregates of SPMs by pi
      pi stacking was proven. SPMs are suitable motifs for the preparation of novel
      fullerene-based donor-acceptor systems. CONCLUSIONS: Alkoxy-decorated SPMs
      represent promising electron-donating building blocks that can be exploited in
      electronics and optoelectronics for the development of robust and highly
      efficient laser-activated supramolecular switches.

PMID- 25981542
TI  - Development and characterization of novel 8-plex DiLeu isobaric labels for
      quantitative proteomics and peptidomics.
AB  - RATIONALE: Relative quantification of proteins via their enzymatically digested
      peptide products determines disease biomarker candidate lists in discovery
      studies. Isobaric label-based strategies using TMT and iTRAQ allow for up to 10
      samples to be multiplexed in one experiment, but their expense limits their use.
      The demand for cost-effective tagging reagents capable of multiplexing many
      samples led us to develop an 8-plex version of our isobaric labeling reagent,
      DiLeu. METHODS: The original 4-plex DiLeu reagent was extended to an 8-plex set
      by coupling isotopic variants of dimethylated leucine to an alanine balance group
      designed to offset the increasing mass of the label's reporter group. Tryptic
      peptides from a single protein digest, a protein mixture digest, and
      Saccharomyces cerevisiae lysate digest were labeled with 8-plex DiLeu and
      analyzed via nanospray liquid chromatography/tandem mass spectrometry
      (nanoLC/MS(2) ) on a Q-Exactive Orbitrap mass spectrometer. Characteristics of 8
      plex DiLeu-labeled peptides, including quantitative accuracy and fragmentation,
      were examined. RESULTS: An 8-plex set of DiLeu reagents with 1 Da spaced
      reporters was synthesized at a yield of 36%. The average cost to label eight 100
      ug peptide samples was calculated to be approximately $15. Normalized collision
      energy tests on the Q-Exactive revealed that a higher-energy collisional
      dissociation value of 27 generated the optimum number of high-quality spectral
      matches. Relative quantification of DiLeu-labeled peptides yielded normalized
      median ratios accurate to within 12% of their expected values. CONCLUSIONS: Cost
      effective 8-plex DiLeu reagents can be synthesized and applied to relative
      peptide and protein quantification. These labels increase the multiplexing
      capacity of our previous 4-plex implementation without requiring high-resolution
      instrumentation to resolve reporter ion signals.

PMID- 25981544
TI  - Effects of calcium complexation on heparin-like disaccharides. A combined
      theoretical, tandem mass spectrometry and ultraviolet experiment.
AB  - RATIONALE: In order to shed light on the influence of the Ca(2+) metal cation on
      the structure of heparin-like (Hp) disaccharides, we have explored the gas-phase
      structures of both [Hp, -2H](2-) and [Ca(Hp), -3H](-) ions by coupling
      experimental and theoretical methods. METHODS: The goal of this work was to (i)
      provide new evidence of the metal influence on the Hp structure, which can have
      important biological consequences, and (ii) to study the usefulness of metal
      complexation for the analytical distinction of Hp isomers. Collision-induced
      dissociation (CID) and ultraviolet photodissociation (UVPD) fragments, as well as
      optical spectra recorded in the gas phase for both [Hp, -2H](2-) and [Ca(Hp), 
      3H](-) complexes were compared for I-H, II-S and III-S isomers of Hp. RESULTS: In
      the case of CID fragmentation, a change in the fragmentation pattern was observed
      upon calcium complexation, with respect to deprotonated Hp. CONCLUSIONS:
      Remarkably, when optical spectra are compared in the UV range, the metal effect
      on the carboxylic group absorption can be detected by an unambiguous blue-shift
      (~20 nm).

PMID- 25981545
TI  - Taxonomic relationships of pollens from matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry data using multivariate
      statistics.
AB  - RATIONALE: Matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) has been suggested as a promising tool for the investigation of pollen, but
      the usefulness of this approach for classification and identification of pollen
      species has to be proven by an application to samples of varying taxonomic
      relations. METHOD: MALDI-MS in combination with hierarchical cluster analysis
      (HCA) and principal component analysis (PCA) was used to delineate taxonomic
      relations between plants based on pollen biochemistry. To assess the robustness
      of the approach, pollen of 74 species of the plant orders Fagales and Coniferales
      were probed. RESULTS: Discrimination at the levels of plant order and genus were
      achieved using the whole spectral range. In many cases, different species of the
      same genus could be distinguished. The sources of the spectral/chemical
      differences at the genus level can be understood using PCA. Specifically, typical
      mass regions for exact genus detection were identified. CONCLUSIONS: Our results
      indicate that the chemical information represented by MALDI-TOFMS data is useful
      for reconstructing taxonomic relationships and is complementary to other chemical
      information on pollen from other spectroscopic data.

PMID- 25981546
TI  - Insights into the binding sites of sulforaphane on insulin studied by
      electrospray ionization mass spectrometry.
AB  - RATIONALE: Sulforaphane (SFN) is a natural isothiocyanate, known to reduce the
      risk of cancer and also aortic damage and diabetic cardiomyopathy induced by type
      2 diabetes, etc. A more detailed knowledge on the direct interaction of SFN with
      insulin and its binding sites is necessary for better understanding the role of
      SFN on diabetes. METHODS: Liquid chromatography/electrospray ionization mass
      spectrometry (LC/ESI-MS) and in-source fragmentation experiments were performed
      on a Thermo Exactive orbitrap mass spectrometer. The solution of insulin and SFN
      was incubated and analyzed by mass spectrometry. Isotopic distribution pattern,
      accurate mass values and theoretical product ions were used to analyze the mass
      spectrometry data. The nature of binding of SFN and its binding sites with
      insulin were evaluated by LC/MS data. RESULTS: ESI-MS analysis of the incubated
      solution of insulin and SFN showed 1:1 and 1:2 complexes of [Insulin-SFN]. LC/MS
      analysis revealed that the [Insulin+SFN] complexes were due to covalent binding
      of SFN at two different sites. The in-source fragmentation experiments revealed
      that the SFN is binding to the NH2 groups of N-terminal amino acids of A and B
      chains of insulin. Further study of SFN with insulin reduced with dithiothreitol
      (DTT) showed exclusive modification of cysteines with SFN. CONCLUSIONS: The
      interaction of SFN was studied with insulin using ESI-MS. SFN is found to bind
      covalently with the free NH2 group of the N-terminal of the A and B chains of
      insulin. However, when insulin is reduced SFN preferably binds to SH groups of
      cysteines. Hence, the present study helps in the understanding of the binding
      sites of SFN on insulin.

PMID- 25981547
TI  - Atmospheric pressure anion mass spectrometry: electron affinities and activation
      energies of thermal electron attachment - perfluoromethylcyclohexane, C7F14.
AB  - RATIONALE: Perfluorocarbons such as perfluoromethylcyclohexane (c-C6 F11 -CF3 )
      are important man-made chemicals that have many uses including plasma processing,
      blood substitutes and atmospheric tracers. It is important to know the kinetics
      and thermodynamics of the reactions of thermal electrons with these molecules
      since they are potentially harmful greenhouse gases that can accumulate in the
      atmosphere. METHODS: The least-squares fits of the temperature dependence of
      electron-capture detection and atmospheric pressure negative ion mass
      spectrometry to a kinetic model are used to determine the electron affinities of
      c-C6 F11 -CF3 , activation energies for the formation of c-C6 F10 -CF3 , and c-C6
      F11 anions and single bond dissociation energies. These are supported by semi
      empirical quantum mechanical calculations. These techniques were previously used
      to characterize superoxide, NO and SF6 anions. RESULTS: The literature electron
      affinities: (eV) c-C6 F11 -CF3 , 1.06, c-C6 F10 -CF3 , 3.9, c-C6 F11 , 3.5 and
      D(R1-CF3 ), 3.8; D(R-F), 4.3 are supported. Additional electron affinities for c
      C6 F11 -CF3 , from 0.5 to 1.5 eV are assigned to excited states. The ground state
      electron affinity is 3.0(2) eV from the photodetachment threshold. Pseudo one
      dimensional anionic Morse potentials illustrating the mechanism for the reaction
      of thermal electrons with c-C6 F11 -CF3 are presented. The major anion peaks in
      perfluorokerosene-L are identified. An experimental setup for studying thermal
      electron capture reactions at variable temperatures, pressures and concentrations
      proposed by Herder in 2004 is presented. CONCLUSIONS: There are multiple anions
      of c-C6 F11 -CF3 more stable than the neutral. Electron-capture detection and
      atmospheric pressure negative ion mass spectrometry are effective general methods
      for determining multiple electron affinities similar to the photodetachment,
      flowing afterglow, magnetron, negative surface ionization, swarm and beam
      procedures. Semi-empirical theoretical calculations support experimental results.
      Additional mass analysis studies of reactions of c-C6 F11 -CF3 with electrons
      over a wide range of temperatures, pressures and electron energies are desirable.

PMID- 25981548
TI  - Application of super-resolution reconstruction of sparse representation in mass
      spectrometry imaging.
AB  - RATIONALE: Mass Spectrometry Imaging (MSI) is useful for analyzing biological
      samples directly, as a spatially resolved, label-free technique. Here we present
      a method for super-resolution reconstruction of sparse representation to improve
      resolution of MSI data. METHODS: Air Flow-Assisted Ionization Mass Spectrometry
      Imaging (AFAI-MSI) was used to acquire MSI data from ink samples, thyroid tumour
      samples, rat renal biopsies, and rat brain biopsy samples. Super-resolution
      reconstruction of sparse representation was adopted for the collected MSI data.
      RESULTS: After comparison of the reconstructed high-resolution image and the
      original high-resolution image, it is found that super-resolution reconstruction
      image is closer to the original high-resolution image than the image obtained
      with the interpolation method, and the highest Peak Signal-to-Noise Ratio (PSNR)
      difference value is over 1.4dB. Therefore, the application of the super
      resolution reconstruction technique, based on sparse representation MSI, is
      feasible and effective. CONCLUSIONS: The method proposed here not only improves
      the resolution of MSI in post-data processing, but also acquires fewer sampling
      points at the same resolution, thereby greatly reducing the sampling time, with
      great application value for large-volume sample MSI, high-resolution MSI, etc.

PMID- 25981549
TI  - Generation of aroE overexpression mutant of Bacillus megaterium for the
      production of shikimic acid.
AB  - BACKGROUND: Shikimic acid, the sole chemical building block for the antiviral
      drug oseltamivir (Tamiflu(r)), is one of the potent pharmaceutical intermediates
      with three chiral centers. Here we report a metabolically engineered recombinant
      Bacillus megaterium strain with aroE (shikimate dehydrogenase) overexpression for
      the production of shikimic acid. RESULTS: In a 7 L bioreactor, 4.2 g/L shikimic
      acid was obtained using the recombinant strain over 0.53 g/L with the wild type.
      The enhancement of total shikimate dehydrogenase activity was 2.13-fold higher
      than the wild type. Maximum yield of shikimic acid (12.54 g/L) was obtained with
      fructose as carbon source. It was isolated from the fermentation broth using
      amberlite IRA-400 resin and 89% purity of the product was achieved. CONCLUSION:
      This will add up a new organism in the armory for the fermentation based
      production which is better over plant based extraction and chemical synthesis of
      shikimic acid.

PMID- 25981550
TI  - Use of ultrasound guidance to improve the safety of percutaneous dilatational
      tracheostomy: a literature review.
AB  - Patients in ICUs frequently require tracheostomy for long-term ventilator
      support, and the percutaneous dilatational tracheostomy (PDT) method is preferred
      over surgical tracheostomy. The use of ultrasound (US) imaging to guide ICU
      procedures and interventions has recently emerged as a simple and noninvasive
      tool. The current evidence regarding the applications of US in PDT is
      encouraging; however, the exact role of US-guided dilatational tracheostomy (US
      PDT) remains poorly defined. In this review, we describe the best available
      evidence concerning the safety and efficacy of US-PDT and briefly delineate the
      general principles of US image generation for the airway and of US-PDT
      procedures. 

PMID- 25981551
TI  - Posterior circulation cerebral hyperperfusion syndrome after high flow external
      carotid artery to middle cerebral artery bypass.
AB  - We present the first report, to our knowledge, in which revascularization of the
      middle cerebral artery (MCA) with a high flow extracranial-intracranial procedure
      resulted in symptomatic hyperemia of the posterior circulation. Cerebral
      hyperperfusion syndrome (CHS) is a poorly understood phenomenon that is
      classically seen in the distribution of a revascularized artery. A 37-year-old
      woman presented with a 3 month history of cognitive and speech difficulties,
      persistent headaches, weakness, numbness, and paresthesia which was worse in the
      right extremities and face. She was found to have bilateral watershed infarcts
      worse in the left cerebral hemisphere, severe bilateral stenosis of the
      supraclinoid internal carotid artery, and a small left superior hypophyseal
      aneurysm. The patient underwent left cerebral hemisphere revascularization with a
      high flow external carotid artery to MCA bypass with aneurysm trapping. During
      skin closure, significant changes were seen in her bilateral upper extremity
      motor-evoked potentials. The patient's postoperative exam was noted for an
      intermittent inability to follow commands, bilateral upper extremity weakness,
      vertical nystagmus, and alogia that all dramatically improved with strict blood
      pressure control. Postoperative perfusion imaging revealed posterior circulation
      hyperemia. This patient highlights the potential for hyperemic complications
      outside the revascularized arterial territory. Strict blood pressure control is
      recommended in order to prevent and manage hyperemia-associated symptoms.
      Improving our understanding of CHS may assist in identifying at risk patients and
      at risk arterial territories in order to optimize CHS prevention and management
      strategies.

PMID- 25981553
TI  - Purinergic Signalling in the Reproductive System.
AB  - Purinergic effects in vivo are local, specific, transient, and affect target
      cells in a paracrine or autocrine manner. Purinergic signalling is involved in
      the regulation of numerous functions in the male and female reproductive tract
      organs. Analysis of functional expression of purinoceptors suggests that P2Y2
      receptors are involved in the regulation of luminal fluid secretion in vivo; P2X1
      and P2X2 in the regulation of smooth muscle cell contraction of blood vessels and
      tubular organs; P2X2 in the regulation of sperm cell maturation; P2X3 in
      activation of sensory nerve fibers involved in reflex activities and pain; P2X4
      in the regulation of tight junctional resistance and epithelial transport in
      female reproductive tract epithelia, and in the regulation of luminal
      acidification in the epididymis, vas deferens and probably the vagina and
      ectocervix; P2Y1 and P2Y2 in the regulation of cell proliferation; P2X5 and P2X7A
      in the regulation of epithelial cell terminal differentiation and apoptosis; and
      A1 receptors in the regulation of sperm cell capacitation. Translational studies
      suggested that cellular levels of the P2X7A receptor could be used as a biomarker
      for the early detection of breast, ectocervix, endocervix, endometrial and
      bladder cancers. Data also suggested that the P2X7A mechanism could be used as a
      pharmaceutical target for the prevention and treatment of epithelial neoplasia
      through the induction of apoptosis. 

PMID- 25981552
TI  - Right temporal lobe variant of frontotemporal dementia.
AB  - We present two women with the right temporal lobe variant (RTLV) of
      frontotemporal dementia (FTD) and analyse the clinical features that are
      determined by the anatomical distribution of atrophy. Each of our patients
      displayed different clinical and radiological profiles which were in line with
      findings reported by other authors. One of two patients carries a novel mutation
      in the granulin gene. FTD is heterogeneous with regard to clinical manifestation,
      genetics, distribution of cortical atrophy and underlying disease. Its clinical
      manifestations are related to the distribution of the cortical atrophy. The RTLV
      of FTD is an uncommon entity. There is no consensus about its name despite the
      fact that its clinical and radiological features are well-defined and distinguish
      it from other types of FTD including semantic dementia. 

PMID- 25981555
TI  - Effectiveness of universal parental support interventions addressing children's
      dietary habits, physical activity and bodyweight: A systematic review.
AB  - OBJECTIVES: The evidence regarding effectiveness of parental support
      interventions targeting children's health behaviours is weak. We aimed to review:
      1) effectiveness of universal parental support interventions to promote dietary
      habits, physical activity (PA) or prevent overweight and obesity among children 2
      18years and 2) effectiveness in relation to family socio-economic position.
      METHODS: Thirty five studies from 1990 to 2013 were identified from major
      databases. Quality was assessed by four criteria accounting for selection and
      attrition bias, fidelity to intervention, and outcome measurement methodology,
      categorizing studies as strong, moderate or weak. RESULTS: Four intervention
      types were identified: face-to-face counselling, group education, information
      sent home, and telephone counselling. Face-to-face or telephone counselling was
      effective in changing children's diet, while there was only weak evidence for
      improvement in PA. Sending home information was not effective. Concerning body
      weight, group education seemed more promising than counselling. Intervention
      effectiveness was generally higher in younger compared to older children. In
      groups with low socio-economic position, group-based approaches appeared
      promising. CONCLUSION: In the future efforts should be made to improve reporting
      of intervention content, include a power calculation for the main outcome, the
      use of high quality outcome assessment methodology, and a follow-up period of at
      least 6months.

PMID- 25981557
TI  - Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6
      hydroxy-dopamine-induced apoptosis.
AB  - BACKGROUND AIMS: Stem cells derived from the dental pulp of human exfoliated
      deciduous teeth (SHEDs) have unique neurogenic properties that could be
      potentially exploited for therapeutic use. The importance of paracrine SHED
      signaling for neuro-regeneration has been recognized, but the exact mechanisms
      behind these effects are presently unknown. In the present study, we investigated
      the neuro-protective potential of exosomes and micro-vesicles derived from SHEDs
      on human dopaminergic neurons during oxidative stress-induced by 6-hydroxy
      dopamine (6-OHDA). METHODS: ReNcell VM human neural stem cells were
      differentiated into dopaminergic neurons and treated with 100 MUmol/L of 6-OHDA
      alone or in combination with exosomes or micro-vesicles purified by
      ultracentrifugation from SHEDs cultivated in serum-free medium under two
      conditions: in standard two-dimensional culture flasks or on laminin-coated micro
      carriers in a bioreactor. Real-time monitoring of apoptosis was performed with
      the use of time-lapse confocal microscopy and the CellEvent Caspase-3/7 green
      detection reagent. RESULTS: Exosomes but not micro-vesicles derived from SHEDs
      grown on the laminin-coated three-dimensional alginate micro-carriers suppressed
      6-OHDA-induced apoptosis in dopaminergic neurons by approximately 80% throughout
      the culture period. Strikingly, no such effects were observed for the exosomes
      derived from SHEDs grown under standard culture conditions. CONCLUSIONS: Our
      results suggest that exosomes derived from SHEDs are considered as new potential
      therapeutic tool in the treatment of Parkinson's disease.

PMID- 25981558
TI  - In vitro characterization of human hair follicle dermal sheath mesenchymal
      stromal cells and their potential in enhancing diabetic wound healing.
AB  - BACKGROUND AIMS: Little is published on the characterization and therapeutic
      potential of human mesenchymal cells derived from hair follicle (HF) dermal
      sheath (DS). In this study, we isolated and characterized HF DS-mesenchymal
      stromal cells (DS-MSCs) with respect to the bone marrow mesenchymal stromal cells
      (BM-MSCs). We further tested if DS-MSC-conditioned medium (CM), like what was
      previously reported for BM-MSC CM, has superior wound-healing properties, in both
      in vitro and in vivo wound models compared with skin fibroblast CM. METHODS: DS
      MSCs were isolated from HF and cultured in vitro to assess long-term growth
      potential, colony-forming efficiency (CFE), expression of CD surface markers and
      differentiation potential. The cytokine expression of DS-MSC CM was determined
      through an antibody-based protein array analysis. The wound-healing effects of
      the CM were tested in vitro with the use of human cell cultures and in vivo with
      the use of a diabetic mouse wound model. RESULTS: In vitro results revealed that
      DS-MSCs have high growth capacity and CFE while displaying some phenotypes
      similar to BM-MSCs. DS-MSCs strongly expressed many surface markers expressed in
      BM-MSCs and could also differentiate into osteoblasts, chondrocytes and
      adipocytes. DS-MSCs secreted significantly higher proportions of paracrine
      factors such as interleukin-6 (IL-6), IL-8 and growth-related oncogene. DS-MSC-CM
      demonstrated enhanced wound-healing effects on human skin keratinocytes,
      fibroblasts and endothelial cells in vitro, and the wound-healing time in
      diabetic mice was found to be shorter, compared with vehicle controls.
      CONCLUSIONS: Human HF DS stromal cells demonstrated MSC-like properties and might
      be an alternative source for therapeutic use in wound healing.

PMID- 25981556
TI  - Longitudinal active living research to address physical inactivity and sedentary
      behaviour in children in transition from preadolescence to adolescence.
AB  - BACKGROUND: Children can be highly active and highly sedentary on the same day!
      For instance, a child can spend a couple of hours playing sports, and then spend
      the rest of the day in front of a screen. A focus on examining both physical
      activity and sedentary behaviour throughout the day and in all seasons in a year
      is necessary to generate comprehensive evidence to curb childhood obesity. To
      achieve this, we need to understand where within a city are children active or
      sedentary in all seasons. This active living study based in Saskatoon, Canada,
      aims to understand the role played by modifiable urban built environments in
      mitigating, or exacerbating, seasonal effects on children's physical activity and
      sedentary behaviour in a population of children in transition from preadolescence
      to adolescence. METHODS/DESIGN: Designed as an observational, longitudinal
      investigation this study will recruit 800 Canadian children 10-14 years of age.
      Data will be obtained from children representing all socioeconomic categories
      within all types of neighbourhoods built in a range of urban designs. Built
      environment characteristics will be measured using previously validated
      neighbourhood audit and observational tools. Neighbourhood level socioeconomic
      variables customized to Saskatoon neighbourhoods from 2011 Statistics Canada's
      National Household Survey will be used to control for neighbourhood social
      environment. The validated Smart Cities Healthy Kids questionnaire will be
      administered to capture children's behaviour and perception of a range of factors
      that influence their activity, household (including family socioeconomic
      factors), parental, peer and neighbourhood influence on independent mobility. The
      outcome measures, different intensities of physical activity and sedentary
      behaviour, will be collected using global positioning system equipped
      accelerometers in all four seasons. Each accelerometry cycle will be matched with
      weather data obtained from Environment Canada. Extensive weather data will be
      accessed and classified into one of six distinct air mass categories for each day
      of accelerometry. Computational and spatial analytical techniques will be
      utilized to understand the multi-level influence of environmental exposures on
      physical activity and sedentary behaviour in all seasons. DISCUSSION: This
      approach will help us understand the influence of urban environment on children's
      activity, thus paving the way to modify urban spaces to increase physical
      activity and decrease sedentary behaviour in children in all four seasons. Lack
      of physical activity and rising sedentariness is associated with rising childhood
      obesity, and childhood obesity in turn is linked to many chronic conditions over
      the life course. Understanding the interaction of children with urban spaces will
      reveal new knowledge, and when translated to actions will provide a strong basis
      for informing future urban planning policy.

PMID- 25981559
TI  - Prevalence and resistance patterns of commensal S. aureus in community-dwelling
      GP patients and socio-demographic associations. A cross-sectional study in the
      framework of the APRES-project in Austria.
AB  - BACKGROUND: The aim of the present study was to assess the prevalence and
      resistance of commensal S. aureus in the nasal microbiota of community-dwelling
      persons in Austria, as well as to identify possible associations with socio
      demographic factors. Multi-drug resistance in this population was additionally
      studied. METHOD: This cross-sectional study was conducted within the context of
      the European APRES project. In nine European countries, nasal swabs were
      collected from 32,206 general practice patients who received care for non
      infectious reasons. In Austria, 20 GPs attempted to recruit 200 consecutive
      patients without infectious diseases, with each patient completing demographic
      questionnaires as well as providing a nose swab sample. Isolation,
      identification, and resistance testing of S. aureus were performed. Statistical
      analyses included subgroup analyses and logistic regression models. RESULTS: 3309
      nose swabs and corresponding questionnaires from Austrian subjects were analyzed.
      S. aureus was identified in 16.6 % (n = 549) of nose swabs, of which 70.1 % were
      resistant against one or more antibiotics, mainly penicillin. S. aureus carrier
      status was significantly associated with male sex (OR 1.6; 1.3-2.0), younger age
      (OR 1.3; 1.0-1.8), living in a rural area (OR 1.4; 1.1-1.7) and working in the
      healthcare sector (OR 1.5; 1.0-2.1). Multi-drug resistances were identified in
      13.7 % (n = 75) of the S. aureus carriers and 1.5 % (n = 8) tested positive for
      MRSA. The highest resistance rate was observed against penicillin (64.8 %),
      followed by azithromycin (13.5 %) and erythromycin with 13.3 %. CONCLUSION: This
      study describes the prevalence and resistance patterns of commensal S. aureus in
      community-dwelling persons in Austria and shows that differences exist between
      socio-demographic groups. Demographic associations have been found for S. aureus
      carriers but not for carriers of resistant S. aureus strains. Only two thirds of
      S. aureus strains were found to be resistant against small spectrum penicillin.
      As it is recognized that one of the corner stones for the containment of
      antibiotic resistance is the appropriate prescription of antibiotics in the
      outpatient sector, this finding lends support to the avoidance of prescription of
      broad-spectrum antibiotics to treat S. aureus infections in the community.

PMID- 25981560
TI  - The influence of CTLA-4 single nucleotide polymorphisms on acute kidney allograft
      rejection in Turkish patients.
AB  - Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface protein, which down
      regulates the immune response at CTLA-4/CD28/B7 pathway. We aimed to investigate
      the influence of the -318 C/T, +49 A/G, -1661 A/G and CT60A/G, and CTLA-4 gene
      polymorphisms on acute rejection of kidney allograft in Turkish patients. The
      study design was a case-control study that consists of three groups: Group 1 (n =
      34) represented the kidney transplant (Ktx) recipients who experienced acute
      rejection, Group 2 (n = 47) was randomly assigned Ktx recipients without acute
      rejection, and Group 3 (n = 50) consisting of healthy volunteers to evaluate the
      normal genomic distribution. The polymerase chain reaction-restriction fragment
      length polymorphism technique was used to determine the polymorphisms. Genotype
      and allele frequencies among three groups denoted similar distributions for +49
      A/G, -1661 A/G, and CT60A/G. Conversely, -318 C/T genotype was three times more
      frequent in the acute rejection group than in the non-rejection group (OR = 3.45;
      95%CI = 1.18-10.1, p = 0.015) and two times more frequent than the healthy
      control group (OR = 2.45; 95% CI = 0.98 - 6.11, p = 0.047). Additionally, having
      a T allele at -318 position was significantly associated with acute rejection
      (0.147 vs. 0.043, OR = 3.45; 95% CI = 1.13-10.56, p = 0.02). 318C/T gene
      polymorphism and T allelic variant were found to be associated with increased
      acute rejection risk in Turkish kidney allograft recipients.

PMID- 25981554
TI  - A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
AB  - BACKGROUND: Bronchoscopy is frequently nondiagnostic in patients with pulmonary
      lesions suspected to be lung cancer. This often results in additional invasive
      testing, although many lesions are benign. We sought to validate a bronchial
      airway gene-expression classifier that could improve the diagnostic performance
      of bronchoscopy. METHODS: Current or former smokers undergoing bronchoscopy for
      suspected lung cancer were enrolled at 28 centers in two multicenter prospective
      studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in
      epithelial cells collected from the normal-appearing mainstem bronchus to assess
      the probability of lung cancer. RESULTS: A total of 639 patients in AEGIS-1 (298
      patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of
      43% of bronchoscopic examinations were nondiagnostic for lung cancer, and
      invasive procedures were performed after bronchoscopy in 35% of patients with
      benign lesions. In AEGIS-1, the classifier had an area under the receiver
      operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73
      to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95%
      CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to
      0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI,
      36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity
      of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2,
      independent of lesion size and location. In 101 patients with an intermediate
      pretest probability of cancer, the negative predictive value of the classifier
      was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic
      examination. CONCLUSIONS: The gene-expression classifier improved the diagnostic
      performance of bronchoscopy for the detection of lung cancer. In intermediate
      risk patients with a nondiagnostic bronchoscopic examination, a negative
      classifier score provides support for a more conservative diagnostic approach.
      (Funded by Allegro Diagnostics and others; AEGIS-1 and AEGIS-2 ClinicalTrials.gov
      numbers, NCT01309087 and NCT00746759.).

PMID- 25981561
TI  - Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension
      Associated with Congenital Heart Disease.
AB  - This study aims to estimate plasma levels of acylated ghrelin in children with
      pulmonary hypertension (PH) associated with congenital heart disease (CHD) and to
      correlate the levels of acylated ghrelin with endothelin-1 (ET-1), nitric oxide
      (NO), and clinical hemodynamic parameters. We investigated the plasma
      concentration of acylated ghrelin, ET-1, NO, and the hemodynamic parameters in 20
      children with CHD, 20 children with PH-CHD, and 20 normal children. Plasma
      acylated ghrelin and NO levels were significantly higher in CHD group than in
      control subjects (P < 0.001). Moreover, plasma-acylated ghrelin, ET-1, and NO
      levels were significantly elevated in PH-CHD group compared with the CHD group (P
      < 0.05). In PH-CHD children, plasma-acylated ghrelin levels correlated positively
      with pulmonary artery systolic pressure (PASP; r = 0.740, P < 0.001), pulmonary
      artery diastolic pressure (PADP; r = 0.613, P = 0.004), right ventricular
      systolic pressure (RVSP; r = 0.642, P = 0.002), mean pulmonary arterial
      hypertension (mPAP; r = 0.685, P = 0.001), right ventricle diameter (RVD; r =
      0.473, P = 0.035), pulmonary artery trunk diameter (PAD; r = 0.613, P = 0.004),
      NO (r = 0.463, P = 0.04), and ET-1 (r = 0.524, P = 0.018). Plasma-acylated
      ghrelin levels were elevated both in CHD and in PH-CHD. Increased acylated
      ghrelin levels correlated positively with ET-1, NO, PASP, PADP, RVSP, mPAP, RVD,
      and PAD. Acylated ghrelin may be a new biomarker of PH-CHD.

PMID- 25981562
TI  - Evaluating the Safety of Intraoperative Antiarrhythmics in Pediatric Cardiac
      Surgery Patients.
AB  - Cardiac arrhythmias occurring during the intraoperative period for cardiac
      surgery have been associated with excess morbidity and mortality. Several
      antiarrhythmics have been utilized for the management of intraoperative
      arrhythmias. These antiarrhythmic medications can cause undesirable adverse
      outcomes in the intensive care setting. The incidence and treatment of adult
      intraoperative arrhythmias have been studied. In addition, the prevalence, risk
      factors, and optimal treatment of pediatric postoperative arrhythmias have also
      been studied. However, the literature has not been published on intraoperative
      antiarrhythmia treatment during pediatric cardiac surgery. The purpose of this
      study was to determine the safety of intraoperative antiarrhythmic medications
      utilized in pediatric cardiac surgery patients. This was a retrospective review
      of all patients who received an intraoperative antiarrhythmic in the
      cardiovascular operating room at Texas Children's Hospital. Patients were
      included if they underwent cardiovascular surgery from November 2008 to July 2013
      and were excluded if antiarrhythmics were given intraoperatively for other
      indications (i.e., esmolol for hypertension) or if patients were older than 18
      years of age. Safety of antiarrhythmic treatment was determined by the absence or
      presence of adverse events. Control or recurrence of the arrhythmia was analyzed
      as a secondary measure to help determine antiarrhythmic efficacy. A total of 45
      patients were identified (53.3 % male). Patients were a median of 0.52 years at
      the time of surgery. Primary surgery types were tetralogy of Fallot repair (n =
      6; 13.3 %) and ventricular septal defect closure (n = 5, 11.1 %). Thirty-one
      patients (68.9 %) had documented adverse events after the administration of
      antiarrhythmics. Most of these adverse events occurred after the administration
      of amiodarone (n = 16; 51.6 %) followed by esmolol (n = 15; 48.4 %). Fifty-one
      percent of the arrhythmias resolved in the operating room (n = 23), and nearly
      half (n = 19) of all patients were discharged home on an antiarrhythmic
      medication. A high incidence of adverse events was associated with intraoperative
      administration of antiarrhythmic medications.

PMID- 25981563
TI  - The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility
      Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population.
AB  - Conotruncal heart defects (CTHDS) are a subgroup of congenital heart
      malformations that are considered to be a folate-sensitive birth defect. It has
      been hypothesized that polymorphisms in genes that code for key enzymes in the
      folate pathway may alter enzyme activity, leading to disruptions in folate
      metabolism and thus may influence the risk of such heart defects. This study was
      designed to investigate the association of six selected folate-metabolizing gene
      polymorphisms with the risk of non-syndromic CTHDs in an Indian population. This
      was a case-control study involving 96 cases of CTHDs and 100 control samples,
      ranging in age from birth to 18 years. Genotyping using Sanger sequencing was
      performed for six single nucleotide polymorphisms of genes involved in folate
      metabolism. Logistic regression analyses revealed that for the 5,10
      methylenetetrahydrofolate (MTHFR) A1298C polymorphism, the CC variant homozygote
      genotype was associated with a significantly increased risk of CTHDs. The results
      of this study support an association between the inherited MTHFR A1298C genotype
      and the risk of CTHDs in an Indian population.

PMID- 25981564
TI  - Under-recognition of Low Blood Pressure Readings in Patients with Duchenne
      Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD), a recessive sex-linked hereditary disorder, is
      characterized by degeneration, atrophy, and weakness of skeletal and cardiac
      muscle. The purpose of this study was to document the prevalence of abnormally
      low resting BP recordings in patients with DMD in our outpatient clinic. The
      charts of 31 patients with DMD attending the cardiology clinic at Rush University
      Medical Center were retrospectively reviewed. Demographic data, systolic,
      diastolic, and mean blood pressures along with current medications,
      echocardiograms, and documented clinical appreciation and management of low blood
      pressure were recorded in the form of 104 outpatient clinical visits. Blood
      pressure (BP) was classified as low if the systolic and/or mean BP was less than
      the fifth percentile for height for patients aged <=17 years (n = 23). For
      patients >=18 years (n = 8), systolic blood pressure (SBP) <90 mmHg or a mean
      arterial pressure (MAP) <60 mmHg was recorded as a low reading. Patients with
      other forms of myopathy or unclear diagnosis were excluded. Statistical analysis
      was done using PASW version 18. BP was documented at 103 (99.01 %) outpatient
      encounters. Low systolic and mean BP were recorded in 35 (33.7 %) encounters.
      This represented low recordings for 19 (61.3 %) out of a total 31 patients with
      two or more successive low recordings for 12 (38.7 %) patients. Thirty-one low BP
      encounters were in patients <18 years old. Hispanic patients accounted for 74
      (71.2 %) visits and had low BP recorded in 32 (43.2 %) instances. The patients
      were non-ambulant in 71 (68.3 %) encounters. Out of 35 encounters with low BP, 17
      patients (48.6 %) were taking heart failure medication. In instances when
      patients had low BP, 22 (66.7 %) out of 33 echocardiography encounters had normal
      left ventricular ejection fraction. Clinician comments on low BP reading were
      present in 11 (10.6 %) encounters, and treatment modification occurred in only 1
      (1 %) patient. Age in years (p = .031) and ethnicity (p = .035) were independent
      predictors of low BP using stepwise multiple regression analysis. Low BP was
      recorded in a significant number of patient encounters in patients with DMD. Age
      17 years or less and Hispanic ethnicity were significant predictors associated
      with low BP readings in our DMD cohort. Concomitant heart failure therapy was not
      a statistically significant association. There is a need for enhanced awareness
      of low BP in DMD patients among primary care and specialty physicians. The
      etiology and clinical impact of these findings are unclear but may impact
      escalation of heart failure therapy.

PMID- 25981565
TI  - Heterogeneity of Ventricular Sympathetic Nervous Activity is Associated with
      Clinically Relevant Ventricular Arrhythmia in Postoperative Patients with
      Tetralogy of Fallot.
AB  - This study aimed to clarify whether there is an association between ventricular
      sympathetic nervous activity (SNA) and clinically relevant ventricular arrhythmia
      (a run of >= 3 consecutive ventricular beats, RVA) in postoperative patients with
      tetralogy of Fallot (TOF). We performed a retrospective study in a national
      referral center of pediatric cardiology in Japan. Twenty-four postoperative TOF
      patients (13 males, median age 17 years) undergoing myocardial (123)I
      metaiodobenzylguanidine (MIBG) scintigraphy were included. We measured the heart
      to-mediastinum ratio (HMR) and washout ratio (WR) from planar MIBG myocardial
      scintigraphy. Tomographic images and polar maps were generated with 20 segments.
      The standard deviation of percentage uptake of 20 segments (SD-uptake) as an
      index of heterogeneous MIBG uptake to the ventricular myocardium was calculated.
      We compared these MIBG-derived variables with the patients' clinical profiles,
      including ECG findings and hemodynamics. Eight of 24 patients had RVA (RVA
      group), and the other 16 did not have RVA (non-RVA group). There were no
      significant differences in the HMR (1.9 +/- 0.5 vs. 2.2 +/- 0.4) and WR (50 +/- 5
      vs. 42 +/- 10) between the two groups. SD-uptake was significantly higher in the
      RVA group than in the non-RVA group (15 +/- 3 vs. 12 +/- 3, p = 0.03). QT
      dispersion (ms) was also higher in the RVA group than in the non-RVA group (53 +/
      23 vs. 44 +/- 18, p = 0.04). Multivariate logistic regression showed that SD
      uptake and QT dispersion were independent predictors in the RVA group (p = 0.02,
      p = 0.03). In addition to greater QT dispersion, heterogeneous SNA is associated
      with RVA in TOF patients postoperatively.

PMID- 25981566
TI  - Incomplete RV Remodeling After Transcatheter ASD Closure in Pediatric Age.
AB  - Published data showing the intermediate effect of transcatheter device closure of
      atrial septal defect (ASD) in the pediatric age-group are scarce. The objective
      of the study was to assess the effects of transcatheter ASD closure on right and
      left ventricular functions by tissue Doppler imaging (TDI). The study included 37
      consecutive patients diagnosed as ASD secundum by transthoracic echocardiography
      and TEE and referred for transcatheter closure at Cairo University Specialized
      Pediatric Hospital, Egypt, from October 2010 to July 2013. Thirty-seven age- and
      sex-matched controls were selected. TDI was obtained using the pulsed Doppler
      mode, interrogating the right cardiac border (the tricuspid annulus) and lateral
      mitral annulus, and myocardial performance index (MPI) was calculated at 1-, 3-,
      6- and 12-month post-device closure. Transcatheter closure of ASD and
      echocardiographic examinations were successfully performed in all patients. There
      were no significant differences between two groups as regards the age, gender,
      weight or BSA. TDI showed that patients with ASD had significantly prolonged
      isovolumetric contraction, relaxation time and MPI compared with control group.
      Decreased tissue Doppler velocities of RV and LV began at one-month post-closure
      compared with the controls. Improvement in RVMPI and LVMPI began at 1-month post
      closure, but they are still prolonged till 1 year. Reverse remodeling of right
      and left ventricles began 1 month after transcatheter ASD closure, but did not
      completely normalize even after 1 year of follow-up by tissue Doppler imaging.

PMID- 25981567
TI  - Exercise Performance in Children and Young Adults After Complete and Incomplete
      Repair of Congenital Heart Disease.
AB  - Few previous studies have addressed exercise capacity in patients with corrected
      congenital heart disease (CHD) and significant anatomical residua. The aim of
      this study was to determine the aerobic fitness and peak cardiac function of
      patients with corrected CHD with complete or incomplete repairs, as determined by
      resting echocardiography. Children, adolescents and young adults (<40 years) with
      CHD from both sexes, who had previously undergone biventricular corrective
      therapeutic interventions (n = 73), and non-CHD control participants (n = 76)
      underwent cardiopulmonary exercise testing. The CHD group was further divided
      according to the absence/presence of significant anatomical residua on a resting
      echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and
      cardiac function were compared between groups using linear regression and
      analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory
      threshold were significantly lower in CHD patients compared with controls (all p
      < 0.01). Compared with the complete repair group, the incomplete repair group had
      a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as %
      predicted) and a higher VE/VCO2 ratio (all p <= 0.05). Peak oxygen consumption
      was comparable between the subgroups. Patients after corrected CHD have lower
      peak and submaximal exercise parameters. Patients with incomplete repair of their
      heart defect had decreased aerobic fitness, with evidence of impaired peak
      cardiac function and lower pulmonary perfusion. Patients that had undergone a
      complete repair had decreased aerobic fitness attributed only to deconditioning.
      These newly identified differences explain why in previous studies, the lowest
      fitness was seen in patients with the most hemodynamically significant heart
      malformations. 

PMID- 25981568
TI  - Functional Analysis of Two Novel Mutations in TWIST1 Protein Motifs Found in
      Ventricular Septal Defect Patients.
AB  - The aim of this study was to investigate the possible genetic effect of sequence
      variations in TWIST1 on the pathogenesis of ventricular septal defect in humans.
      We examined the coding region of TWIST1 in a cohort of 196 Chinese people with
      non-syndromic ventricular septal defect patients and 200 healthy individuals as
      the controls. We identified two novel potential disease-associated mutations,
      NM_000474.3:c.247G>A (G83S) and NM_000474.3:c.283A>G (S95G). Both of them were
      identified for the first time and were not observed in the 200 controls without
      congenital heart disease. Using a dual-luciferase reporter assay, we showed that
      both of the mutations significantly down-regulated the repressive effect of
      TWIST1 on the E-cadherin promoter. Furthermore, a mammalian two-hybrid assay
      showed that both of the mutations significantly affected the interaction between
      TWIST1 and KAT2B. New mutations in the transcription factor TWIST1 that affect
      protein function were identified in 1.0 % (2/196) of Chinese patients with
      ventricular septal defect. Our data show, for the first time, that TWIST1 has a
      potential causative effect on the development of ventricular septal defect. 

PMID- 25981569
TI  - The impact of inpatient rivaroxaban versus warfarin on hospital-based outcomes
      when used for stroke prevention in patients with anticoagulant naive, new-onset
      nonvalvular atrial fibrillation.

PMID- 25981570
TI  - Prolonged intra-aortic balloon pump support in biventricular heart failure
      induces right ventricular reverse remodeling.
AB  - BACKGROUND: Right ventricular dysfunction is associated with high morbidity and
      mortality in candidates for left ventricular assist device (LVAD) implantation or
      cardiac transplantation. METHODS: We examined the effects of prolonged intra
      aortic balloon pump (IABP) support on right ventricular, renal and hepatic
      functions in patients presenting with end-stage heart failure. RESULTS: Between
      March 2008 and June 2013, fifteen patients (mean age = 49.5 years; 14 men) with
      end-stage systolic heart failure (HF), contraindications for any life saving
      procedure (conventional cardiac surgery, heart transplantation, LVAD
      implantation) and right ventricular dysfunction were supported with the IABP. The
      patients remained on IABP support for a mean of 73 +/- 50 days (median 72, range
      of 13-155). We measured the echocardiographic and hemodynamic changes in right
      ventricular function, and the changes in serum creatinine and bilirubin
      concentrations before and during IABP support. Mean right atrial pressure
      decreased from 12.7 +/- 6.5 to 3.8 +/- 3.3 (P < 0.001) and pulmonary artery
      pressure decreased from 35.7 +/- 10.6 to 25 +/- 8.4 mmHg (P = 0.001), while
      cardiac index increased from 1.5 +/- 0.4 to 2.2 +/- 0.7 l/m(2)/min (P = 0.003)
      and right ventricular stroke work index from 485 +/- 228 to 688 +/- 237 mmHg *
      ml/m(2) (P = 0.043). Right ventricular end-diastolic diameter decreased from 34.0
      +/- 6.5 mm to 27.8 +/- 6.2 mm (P < 0.001) and tricuspid annular systolic tissue
      Doppler velocity increased from 9.6 +/- 2.4 cm/s to 11.1 +/- 2.3 cm/s (P =
      0.029). Serum creatinine and bilirubin decreased from 2.1 +/- 1.3 to 1.4 +/- 0.6
      mg/dl and 2.0 +/- 1.0 to 0.9 +/- 0.5 mg/dl, respectively (P = 0.002 and P <
      0.001, respectively). CONCLUSIONS: Prolonged IABP support of patients presenting
      with end-stage heart failure and right ventricular dysfunction induced
      significant improvement in right ventricular and peripheral organ function.

PMID- 25981571
TI  - The influence of autonomic nervous system on the conduction system and heart
      muscle. Do different inhaled bronchodilators cause different tachyarrhythmias?

PMID- 25981572
TI  - Ticagrelor-related gout: An underestimated side effect.

PMID- 25981573
TI  - Novel microRNAs involved in regulation of cardiac fibrosis.

PMID- 25981574
TI  - Cardioembolic acute myocardial infarction associated with apical ballooning:
      Considerations.

PMID- 25981575
TI  - A successful retrieval of entrapped guidewire with a novel "jailed-wire
      technique".

PMID- 25981576
TI  - First case of subcutaneous implantable cardioverter-defibrillator extrusion.

PMID- 25981577
TI  - Pericardial effusion and heart failure.

PMID- 25981578
TI  - Circulating corin concentrations are related to infarct size in patients after ST
      segment elevation myocardial infarction.

PMID- 25981579
TI  - A Very Rare Cerebral Complication of Chemotherapy in a Young Girl: A Difficult
      Diagnosis.
AB  - Sagittal sinus thrombosis (SST) induced by chemotherapy is exceptional. We
      describe here a new case following the fourth cure of chemotherapy based on
      cisplatin, bleomycin and etoposide in a 16-year-old patient with no obvious risk
      factors. Through this uncommon case which forms part of cerebral venous sinus
      thrombosis (CVST), we propose to study the pathophysiology, the diagnosis and the
      management of this entity. The exclusion of the other causes of CVST is important
      not only for the therapeutic implication but also for the prognosis. Then,
      accurate documentation of each case induced by chemotherapy is needed to further
      understanding. 

PMID- 25981580
TI  - Characterization of a Thermostable Uricase Isolated from Bacillus firmus DWD-33
      and its Application for Uric Acid Quantification in Human Serum.
AB  - A thermostable uricase identified in Bacillus firmus DWD-33, which was isolated
      for the first time from soil, with an apparent molecular weight of 33.5 kDa was
      stable against oxidants and SDS. The highest expression yields were obtained in
      medium containing 0.8% maltose and 1.2% soybean powder as carbon and nitrogen
      sources, respectively. Enzyme purification increased the specific activity about
      24-fold with 27% recovery. As compared with other microbial uricases, the pure
      enzyme showed a high thermostability. The Vmax was 387 umol/L/min, the turnover
      number (Kcat) was 21.8x10(3) s(-1) and the catalytic efficiency (Kcat /Km) was
      2.76x10(8) s(-1)M(-1). The enzyme was stable from pH 7.0 to 10.0 and up to 70 
      degrees C and the optimal conditions were 50  degrees C and pH 8.0. Mg(2+)
      significantly enhanced the enzymatic activity, while Hg(2+), EDTA, and o
      phenanthroline greatly suppressed the activity. Mg(2+) might be the uricase
      cofactor, as the enzyme activity was restored after its addition to EDTA-chelated
      enzyme. Inhibition of the enzyme by the copper- chelating agent 2,9-dimethyl-1,10
      phenanthroline suggests that this enzyme belongs to the cuprouricase-type. The
      purified uricase retained 72% and 82% of its original activity after incubation
      with 0.5% H2O2 and 0.5% SDS for 6 h, respectively. It was possible to determine
      uric acid in human sera with the enzyme with none of the tested uric acid analogs
      being a competitive substrate, indicating a high specificity of uricase with
      respect to uric acid measurement in vitro for uric acid concentration up to 500
      umol/L. 

PMID- 25981581
TI  - Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating
      ROS-mediated MAPKs and PI3K/AKT signaling pathways.
AB  - Both phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein
      kinase (MAPK) signaling cascades play an important role in cell proliferation,
      survival, angiogenesis, and metastasis of tumor cells. In the present report, we
      investigated the effects of licochalcone A (LA), a flavonoid extracted from
      licorice root, on the PI3K/AKT/mTOR and MAPK activation pathways in human gastric
      cancer BGC-823 cells. LA increased reactive oxygen species (ROS) levels, which is
      associated with the induction of apoptosis as characterized by positive Annexin V
      binding and activation of caspase-3, and cleavage of poly-ADP-ribose polymerase
      (PARP). Inhibition of ROS generation by N-acetylcysteine (NAC) significantly
      prevented LA-induced apoptosis. Interestingly, we also observed that LA caused
      the activation of ERK, JNK, and p38 MAPK in BGC-823 cells. The antitumour
      activity of LA-treated BGC-823 cells was significantly distinct in KM mice in
      vivo. All the findings from our study suggest that LA can interfere with MAPK
      signaling cascades, initiate ROS generation, induce oxidative stress and
      consequently cause BGC cell apoptosis. 

PMID- 25981583
TI  - Amberinone, a new guaianolide from Amberboa ramosa.
AB  - The Amberboa is a medicinally important genus present in the family Asteraceae;
      members of this genus are mainly distributed in Pakistan and India. It has been
      used in different systems of traditional medicines for different diseases.
      Amberinone (1), a new sesquiterpene lactone, has been isolated from the ethyl
      acetate (EtOAc) soluble fraction of Amberboa ramosa together with chrysin (2),
      quercitine (3), eriodictyol (4) and keamferol (5). This is the first report of
      these compounds from this species. The structures of the isolated compounds have
      been elucidated by 1D and 2D (1)H (13)C NMR spectroscopy. 

PMID- 25981582
TI  - A functional variant at miRNA-122 binding site in IL-1alpha 3' UTR predicts risk
      and HPV-positive tumours of oropharyngeal cancer.
AB  - BACKGROUND: Genetic polymorphisms in the 3' untranslated regions (3' UTRs)
      targeted by miRNAs alter the strength of miRNA binding in a manner that affects
      the behaviour of individual miRNAs. An insertion (Ins)/deletion (Del)
      polymorphism (rs3783553) in the 3' UTR of IL-1alpha may disrupt a binding site
      for miRNA-122. IL-1alpha plays an important role in inflammation, immunity and
      defense against infection. Thus, we hypothesised that the rs3783553 polymorphism
      affects individual susceptibility to human papillomavirus (HPV)-associated oral
      squamous cell carcinoma (OSCC). METHODS: We genotyped the rs3783553 polymorphism;
      and determined HPV16 L1 serology, tumour HPV16 DNA and serum IL-1alpha
      expression. Univariate/multivariable logistic regression models were used to
      calculate associations. RESULTS: We found that HPV16 L1 seropositivity alone was
      associated with an increased risk of OSCC (Odds ratio (OR), 3.1; 95% confidence
      interval (CI), 2.1-4.6), and the risk of HPV16-associated OSCC was modified by
      the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and
      Del/Del genotype for the rs3783553 had the highest risk of OSCC when using
      patients with HPV16 L1 seronegativity and Ins/Del+Ins/Ins genotypes as a
      comparison group. Notably, that effect modification was particularly pronounced
      in several subgroups (e.g. SCCOP, never-smokers and never-drinkers). The patients
      with Del/Del genotype were approximately 3.0 times more likely to have HPV16
      positive squamous cell carcinoma of the oropharynx (SCCOP) tumours compared to
      those patients with Ins/Del+Ins/Ins genotypes. Additionally, functional relevance
      of this variant was characterised to explore the genotype-phenotype correlation.
      CONCLUSION: These results suggest that IL-1alpha 3' UTR rs3783553 polymorphism
      may be functional and influence susceptibility to HPV16-associated OSCC,
      particularly for SCCOP. Validation of our findings is warranted.

PMID- 25981584
TI  - Cobalt protoporphyrin represses osteoclastogenesis through blocking multiple
      signaling pathways.
AB  - Cobalt protoporphyrin (CoPP) is a metallo-protoporphyrin that works as a powerful
      inducer of heme oxigenase-1 (HO-1) in various tissues and cells. Our recent
      studies have demonstrated that induction of HO-1 by several reagents inhibited
      differentiation and activation of osteoclasts (OCLs), which are multinucleated
      bone resorbing cells. However, the effects of CoPP on osteoclastogenesis remain
      to be elucidated. In this study, we report that CoPP inhibits receptor activator
      of nuclear factor kappaB ligand (RANKL)-induced OCL formation in a dose dependent
      manner. Importantly, CoPP had little cytotoxicity, but rather enhanced cell
      proliferation of OCLs. CoPP suppressed the protein levels of nuclear factor of
      activated T cells cytoplasmic-1 (NFATc1) as well as those of OCLs markers such as
      Src and cathepsin K, which are transcriptionally regulated by NFATc1 in mature
      OCLs. Western blot analyses also showed that CoPP abolished RANKL-stimulated
      phosphorylation of several major signaling pathways such as IkappaB, Akt, ERK,
      JNK and p38 MAPKs in OCL precursor cells. Thus, our results show that CoPP
      represses osteoclastogenesis through blocking multiple signaling pathways. 

PMID- 25981585
TI  - A community-based participatory research methodology to address, redress, and
      reassess disparities in respiratory health among First Nations.
AB  - BACKGROUND: To date, determinants of respiratory health in First Nations people
      living on reserves and means of addressing and redressing those determinants have
      not been well established. Hence the Saskatchewan First Nations Lung Health
      Project (FNLHP) is a new prospective cohort study of aboriginal people being
      conducted in two First Nations reserves to evaluate potential health determinants
      associated with respiratory outcomes. Using the population health framework (PHF)
      of Health Canada, instruments designed with the communities, joint ownership of
      data, and based on the 4-phase concept of the First Nations Regional Longitudinal
      Health Survey, the project aims to evaluate individual factors, contextual
      factors, and principal covariates on respiratory outcomes. The objective of this
      report is to clearly describe the methodology of (i) the baseline survey that
      consists of two components, an interviewer-administered questionnaire and
      clinical assessment; and (ii) potential intervention programs; and present
      descriptive results of the baseline data of longitudinal FNLHP. METHODS: The
      study is being conducted over 5 years (2012-2017) in two phases, baseline and
      longitudinal. Baseline survey has been completed and consisted of (i) an
      interviewer-administered questionnaire-based evaluation of individual and
      contextual factors of importance to respiratory health (with special focus on
      chronic bronchitis, chronic obstructive pulmonary disease, asthma and obstructive
      sleep apnea), and (ii) clinical lung function and allergy tests with the consent
      of study participants. The address-redress phase consists of potential
      intervention programs and is currently being rolled out to address-at community
      level (via green light program and environmental study), and redress-at policy
      level (via obesity reduction and improved diagnosis and treatment of obstructive
      sleep apnea) the issues that have been identified by the baseline data. RESULTS:
      Interviewer-administered surveys were conducted in 2012-2013 and collected data
      on 874 individuals living in 406 households from two reserve communities located
      in Saskatchewan, Canada. Four hundred and forty six (51%) females and 428 (49%)
      males participated in the FNLHP. CONCLUSIONS: The information from this project
      will assist in addressing and redressing many of the issues involved including
      the provision of adequate housing, health lifestyle practices, and in planning
      for health service delivery.

PMID- 25981586
TI  - Single-molecule sequencing reveals the molecular basis of multidrug-resistance in
      ST772 methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause
      of hospital-associated infection, but there is growing awareness of the emergence
      of multidrug-resistant lineages in community settings around the world. One such
      lineage is ST772-MRSA-V, which has disseminated globally and is increasingly
      prevalent in India. Here, we present the complete genome sequence of DAR4145, a
      strain of the ST772-MRSA-V lineage from India, and investigate its genomic
      characteristics in regards to antibiotic resistance and virulence factors.
      RESULTS: Sequencing using single-molecule real-time technology resulted in the
      assembly of a single continuous chromosomal sequence, which was error-corrected,
      annotated and compared to nine draft genome assemblies of ST772-MRSA-V from
      Australia, Malaysia and India. We discovered numerous and redundant resistance
      genes associated with mobile genetic elements (MGEs) and known core genome
      mutations that explain the highly antibiotic resistant phenotype of DAR4145.
      Staphylococcal toxins and superantigens, including the leukotoxin Panton
      Valentinin Leukocidin, were predominantly associated with genomic islands and the
      phage phi-IND772PVL. Some of these mobile resistance and virulence factors were
      variably present in other strains of the ST772-MRSA-V lineage. CONCLUSIONS: The
      genomic characteristics presented here emphasize the contribution of MGEs to the
      emergence of multidrug-resistant and highly virulent strains of community
      associated MRSA. Antibiotic resistance was further augmented by chromosomal
      mutations and redundancy of resistance genes. The complete genome of DAR4145
      provides a valuable resource for future investigations into the global
      dissemination and phylogeography of ST772-MRSA-V.

PMID- 25981589
TI  - The fiscal crisis in the health sector: Patterns of cutback management across
      Europe.
AB  - PURPOSE: The article investigates trends in health sector cutback management
      strategies occurred during the ongoing financial and fiscal crisis across Europe.
      SETTING: A European-wide survey to top public healthcare managers was conducted
      in ten different countries to understand their perception about public sector
      policy reactions to the financial and economic crisis; answers from 760
      respondents from the healthcare sector (30.7% response rate) were analyzed.
      METHOD: A multinomial logistic regression was used to assess the characteristics
      of respondents, countries' institutional healthcare models and the trend in
      public health resources availability during the crisis associated to the decision
      to introduce unselective cuts, targeted cuts or efficiency savings measures.
      RESULTS: Differentiated responses to the fiscal crisis that buffeted public
      finances were reported both across and within countries. Organizational position
      of respondents is significant in explaining the perceived cutback management
      approach introduced, where decentralized positions detect a higher use of linear
      cuts compared to their colleagues working in central level organizations.
      Compared to Bismark-like systems Beveridge-like ones favour the introduction of
      targeted cuts. Postponing the implementation of new programmes and containing
      expenses through instruments like pay freezes are some of the most popular
      responses adopted, while outright staff layoffs or reduction of frontline
      services have been more selectively employed. CONCLUSION: To cope with the
      effects of the fiscal crisis healthcare systems are undergoing important changes,
      possibly also affecting the scope of universal coverage.

PMID- 25981590
TI  - Integrated health and social care in England--Progress and prospects.
AB  - This paper reviews recent policy initiatives in England to achieve the closer
      integration of health and social care. This has been a policy goal of successive
      UK governments for over 40 years but overall progress has been patchy and
      limited. The coalition government has a new national framework for integrated
      care and variety of new policy initiatives including the 'pioneer' programme, the
      introduction of a new pooled budget--the 'Better Care Fund'--and a new programme
      of personal commissioning. Further change is likely as the NHS begins to develop
      new models of care delivery. There are significant tensions between these very
      different policy levers and styles of implementation. It is too early to assess
      their combined impact. Expectations that integration will achieve substantial
      financial savings are not supported by evidence. Local effort alone will be
      insufficient to overcome the fundamental differences in entitlement, funding and
      delivery between the NHS and the social care system. With a national election set
      to take place in May 2015, all political parties are committed to the integration
      of health and social care but clear evidence about the best means to achieve it
      is likely to remain as elusive as ever.

PMID- 25981588
TI  - Effects of dimethyloxalylglycine on wound healing of palatal mucosa in a rat
      model.
AB  - BACKGROUND: Rapid wound healing of oral soft tissue may reduce the opportunity of
      infection and discomfort of patients. Previous studies have demonstrated that
      enhancement of angiogenesis is an effective way to accelerate wound repair. In
      this study, to enhance angiogenesis and healing of palatal wounds,
      dimethyloxalylglycine (DMOG) was applied to a rat palatal wound model. DMOG is
      known to inhibit oxygen-dependent degradation of hypoxia inducible factor-1 alpha
      (HIF-1alpha), which can lead to up-regulation of angiogenesis markers, favoring
      wound repair. We also evaluated the effects of DMOG on cell migration and HIF
      1alpha expression of rat palatal (RP) cells. Furthermore, mRNA and protein
      expression of vascular endothelial growth factor (VEGF) were analyzed in DMOG
      treated RP cells. METHODS: Primary cultures of rat palatal (RP) cells were
      obtained from Sprague-Dawley (SD) rats. Effects of DMOG on cell viability and
      migration of RP cells were evaluated by using a formazan and culture insert,
      respectively. VEGF mRNA was observed by real-time PCR, and VEGF and HIF-1alpha
      proteins were detected by Western blotting. For the animal study, excisional
      wounds, 3 mm in diameter, were made at the central part of the palate of SD rats.
      DMOG with hyaluronic acid ointment was topically applied three times during 1
      week, and then wound closures were quantitated photographically and
      histologically. RESULTS: DMOG was cytotoxic to RP cells at concentrations higher
      than 2 mM and did not affect cell migration at non-cytotoxic concentrations. mRNA
      and protein expression of VEGF were significantly stimulated by DMOG treatment.
      The protein level of HIF-1alpha was also stabilized in RP cells by DMOG. In the
      animal study, groups treated with 1 mg/ml DMOG showed an increase of rat palatal
      wound contractures. CONCLUSIONS: DMOG enhanced wound healing of rat palatal
      mucosa, which was likely due to the angiogenic effect of the agent.

PMID- 25981587
TI  - Evaluation of 11C-acetate and 18F-FDG PET/CT in mouse multidrug resistance gene-2
      deficient mouse model of hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) remains a global health problem with
      unique diagnostic and therapeutic challenges, including difficulties in
      identifying the highest risk patients. Previous work from our lab has established
      the murine multidrug resistance-2 mouse (MDR2) model of HCC as a reasonable
      preclinical model that parallels the changes seen in human inflammatory
      associated HCC. The purpose of this study is to evaluate modalities of PET/CT in
      MDR2(-/-) mice in order to facilitate therapeutic translational studies from
      bench to bedside. METHODS: 18F-FDG and 11C-acetate PET/CT was performed on 12 m
      MDR2(-/-) mice (n = 3/tracer) with HCC and 12 m MDR2(-/+) control mice (n =
      3/tracer) without HCC. To compare PET/CT to biological markers of HCC and
      cellular function, serum alpha-fetoprotein (AFP), lysophosphatidic acid (LPA),
      cAMP and hepatic tumor necrosis factor alpha (TNFalpha) were quantified in 3-12 m
      MDR2(-/-) (n = 10) mice using commercially available ELISA analysis. To translate
      results in mice to patients 11C-acetate PET/CT was also performed in 8 patents
      suspected of HCC recurrence following treatment and currently on the liver
      transplant wait list. RESULTS: Hepatic18F-FDG metabolism was not significantly
      increased in MDR2(-/-) mice. In contrast, hepatic 11C-acetate metabolism was
      significantly elevated in MDR2(-/-) mice when compared to MDR2(-/+) controls.
      Serum AFP and LPA levels increased in MDR2(-/-) mice contemporaneous with the
      emergence of HCC. This was accompanied by a significant decrease in serum cAMP
      levels and an increase in hepatic TNFalpha. In patients suspected of HCC
      recurrence there were 5 true positives, 2 true negatives and 1 suspected false
      11C-acetate negative. CONCLUSIONS: Hepatic 11C-acetate PET/CT tracks well with
      HCC in MDR2(-/-) mice and patients with underlying liver disease. Consequently
      11C-acetate PET/CT is well suited to study (1) HCC emergence/progression in
      patients and (2) reduce animal numbers required to study new chemotherapeutics in
      murine models of HCC.

PMID- 25981591
TI  - CDH1 germ-line missense mutation identified by multigene sequencing in a family
      with no history of diffuse gastric cancer.
AB  - Germ-line mutation in CDH1 gene is associated with high risk for Hereditary
      Diffuse Gastric Cancer (HDGC) and Infiltrative Lobular Carcinoma (ILC). Although
      somatic CDH1 mutations were also detected in ILC with a frequency ranging from 10
      to 56%, CDH1 alterations in more frequent infiltrative ductal carcinoma (IDC)
      appear to be rare, and no association with germ-line CDH1 mutation and IDC has
      been established. Here we report the case of a woman diagnosed with IDC at
      39years of age, presenting extensive familial history of cancer at multiple sites
      with early-age onset and with no case of HDGC. Deep sequencing have revealed CDH1
      missense mutation c.1849G>A (p.Ala617Thr) in heterozygous and four BRCA2 single
      nucleotide polymorphism in homozygosis. In this family, the mutation c.1849G>A in
      the CDH1 gene is not related to HDGC nor ILC. Therefore, here we highlight that
      multigene analysis is important to detect germ-line mutations and genetic
      variants in patients with cancers at multiple sites in the family, even if
      inconclusive genetic counseling can be offered, since hereafter, medical
      awareness will be held.

PMID- 25981592
TI  - Identification and characterisation of synaptonemal complex genes in monotremes.
AB  - The platypus and echidna are the only extant species belonging to the clade of
      monotremata, the most basal mammalian lineage. The platypus is particularly well
      known for its mix of mammalian and reptilian characteristics and work in recent
      years has revealed this also extends to the genetic level. Amongst the monotreme
      specific features is the unique multiple sex chromosome system (5X4Y in the
      echidna and 5X5Y in the platypus), which forms a chain in meiosis. This raises
      questions about sex chromosome organisation at meiosis, including whether there
      has been changes in genes coding for synaptonemal complex proteins which are
      involved in homologous synapsis. Here we investigate the key structural
      components of the synaptonemal complex in platypus and echidna, synaptonemal
      complex proteins 1, 2 and 3 (SYCP1, SYCP2 and SYCP3). SYCP1 and SYCP2 orthologues
      are present, conserved and expressed in platypus testis. SYCP3 in contrast is
      highly diverged, but key residues required for self-association are conserved,
      while those required for tetramer stabilisation and DNA binding are missing. We
      also discovered a second SYCP3-like gene (SYCP3-like) in the same region.
      Comparison with the recently published Y-borne SYCP3 amino acid sequences
      revealed that SYCP3Y is more similar to SYCP3 in other mammals than the monotreme
      autosomal SYCP3. It is currently unclear if these changes in the SYCP3 gene
      repertoire are related to meiotic organisation of the extraordinary monotreme sex
      chromosome system. 

PMID- 25981593
TI  - Molecular cloning and characterization of the matricellular protein
      Sparc/osteonectin in flatfish, Scophthalmus maximus, and its developmental stage
      dependent transcriptional regulation during metamorphosis.
AB  - SPARC/osteonectin is a multifunctional matricellular glycoprotein, which is
      expressed in embryonic and adult tissues that undergo active proliferation and
      dynamic morphogenesis. Recent studies indicate that Sparc expression appears
      early in development, although its function and regulation during development are
      largely unknown. In this report, we describe the isolation, characterization,
      post-embryonic developmental expression and environmental thermal regulation of
      sparc in turbot. The full-length turbot sparc cDNA contains 930 bp and encodes a
      protein of 310 amino acids, which shares 77, 75 and 80% identity with human, frog
      and zebrafish, respectively. Results of whole-mount in situ hybridization reveal
      a dynamic expression profile during post-embryonic turbot development. Sparc is
      expressed differentially in the cranioencephalic region; mainly in jaws,
      branchial arches, fin folds and rays of caudal, dorsal and anal fins.
      Furthermore, ontogenetic studies demonstrated that Sparc gene expression is
      dynamically regulated during post-embryonic turbot development, with high
      expression during stage-specific post-embryonic remodeling. Additionally, the
      effect of thermal environmental conditions on turbot development and on
      ontogenetic sparc expression was evaluated.

PMID- 25981594
TI  - Effect of MTHFR, TGFbeta1, and TNFB polymorphisms on osteoporosis in rheumatoid
      arthritis patients.
AB  - Diseases of the immune and the skeletal systems should be studied together for
      the deep interaction between them. Many studies consider osteoporosis (OP) as a
      risk factor for the prediction of disease progression in rheumatoid arthritis
      (RA). The aim of this research is to study the effect of four single nucleotide
      polymorphisms (SNPs) on RA patients with and without OP. The examined SNPs (MTHFR
      (C677T, and A1298C), TGFbeta1 (T869C), and TNFB (A252G)) were tested by
      genotyping 17 RA patients with OP and 72 RA patients without OP. Associations
      were tested using four models (multiplicative, dominant, recessive, and co
      dominant). The studied SNPs were not significantly associated with the risk of OP
      in RA. MTHFR, TGFbeta1, and TNFB polymorphisms don't appear to be clinically
      useful genetic markers for predicting RA severity in Egyptian women population.

PMID- 25981596
TI  - Perceptions of Italian student nurses of the concept of professional respect
      during their clinical practice learning experience.
AB  - This research explored the perceptions of third-year undergraduate nursing
      students in Italy in relation to the perceptions they had about factors that
      promoted or diminished the development of professional identity and the
      professional respect in themselves, and in nursing during their clinical
      training. Clinical training was meaningful to develop specific knowledge,
      communication skills, and interpersonal and inter-professional relationships in
      the area considered. It was also found to be equally important to have good role
      models to foster the moral development and build a solid professional identity
      for nursing students. Building a professional identity is an ongoing process and
      depends on social contexts and on the students' development of the ability to act
      morally. In this framework, student nurses have to be strongly supported to
      develop their identity as moral agents in spite of the conflicting demands on
      them in hostile settings that often do not make them feel respected for their
      actions. Based on our evidence, we identified two conceptual areas: positive role
      models and supportive working environments; both have to be strongly connected
      each other if the student nurses have to develop a strong respect for the ethical
      values of their profession. 

PMID- 25981595
TI  - Bacterial xylose isomerases from the mammal gut Bacteroidetes cluster function in
      Saccharomyces cerevisiae for effective xylose fermentation.
AB  - BACKGROUND: Xylose isomerase (XI) catalyzes the conversion of xylose to xylulose,
      which is the key step for anaerobic ethanolic fermentation of xylose. Very few
      bacterial XIs can function actively in Saccharomyces cerevisiae. Here, we
      illustrate a group of XIs that would function for xylose fermentation in S.
      cerevisiae through phylogenetic analysis, recombinant yeast strain construction,
      and xylose fermentation. RESULTS: Phylogenetic analysis of deposited XI sequences
      showed that XI evolutionary relationship was highly consistent with the bacterial
      taxonomic orders and quite a few functional XIs in S. cerevisiae were clustered
      with XIs from mammal gut Bacteroidetes group. An XI from Bacteroides valgutus in
      this cluster was actively expressed in S. cerevisiae with an activity comparable
      to the fungal XI from Piromyces sp. Two XI genes were isolated from the
      environmental metagenome and they were clustered with XIs from environmental
      Bacteroidetes group. These two XIs could not be expressed in yeast with activity.
      With the XI from B. valgutus expressed in S. cerevisiae, background yeast strains
      were optimized by pentose metabolizing pathway enhancement and adaptive evolution
      in xylose medium. Afterwards, more XIs from the mammal gut Bacteroidetes group,
      including those from B. vulgatus, Tannerella sp. 6_1_58FAA_CT1, Paraprevotella
      xylaniphila and Alistipes sp. HGB5, were individually transformed into S.
      cerevisiae. The known functional XI from Orpinomyces sp. ukk1, a mammal gut
      fungus, was used as the control. All the resulting recombinant yeast strains were
      able to ferment xylose. The respiration-deficient strains harboring B. vulgatus
      and Alistipes sp. HGB5 XI genes respectively obtained specific xylose consumption
      rate of 0.662 and 0.704 g xylose gcdw(-1) h(-1), and ethanol specific
      productivity of 0.277 and 0.283 g ethanol gcdw(-1) h(-1), much comparable to
      those obtained by the control strain carrying Orpinomyces sp. ukk1 XI gene.
      CONCLUSIONS: This study demonstrated that XIs clustered in the mammal gut
      Bacteroidetes group were able to be expressed functionally in S. cerevisiae and
      background strain anaerobic adaptive evolution in xylose medium is essential for
      the screening of functional XIs. The methods outlined in this paper are
      instructive for the identification of novel XIs that are functional in S.
      cerevisiae.

PMID- 25981597
TI  - Immersive simulated reality scenarios for enhancing students' experience of
      people with learning disabilities across all fields of nurse education.
AB  - Poor preparation of nurses, regarding learning disabilities can have devastating
      consequences. High-profile reports and the Nursing and Midwifery Council
      requirements led this University to introduce Shareville into the undergraduate
      and postgraduate nursing curriculum. Shareville is a virtual environment
      developed at Birmingham City University, in which student nurses learn from
      realistic, problem-based scenarios featuring people with learning disabilities.
      Following the implementation of the resource an evaluation of both staff and
      student experience was undertaken. Students reported that problem-based scenarios
      were sufficiently real and immersive. Scenarios presented previously
      unanticipated considerations, offering new insights, and giving students the
      opportunity to practise decision-making in challenging scenarios before
      encountering them in practice. The interface and the quality of the graphics were
      criticised, but, this did not interfere with learning. Nine lecturers were
      interviewed, they generally felt positively towards the resource and identified
      strengths in terms of blended learning and collaborative teaching. The evaluation
      contributes to understandings of learning via simulated reality, and identifies
      process issues that will inform the development of further resources and their
      roll-out locally, and may guide other education providers in developing and
      implementing resources of this nature. There was significant parity between
      lecturers' expectations of students' experience of Shareville. 

PMID- 25981599
TI  - Fellow-eye neovascularization in unilateral retinal angiomatous proliferation in
      a Korean population.
AB  - PURPOSE: To evaluate the incidence of fellow-eye neovascularization in retinal
      angiomatous proliferation (RAP) in a Korean population and associated risk
      factors. METHOD: This retrospective, observational study included 81 eyes (81
      patients) diagnosed with unilateral RAP who were followed up for >=12 months. The
      RAP diagnosis was based on an indocyanine green angiography reviewed by two
      retinal specialists. In fellow eyes experiencing neovascularization, the period
      between RAP diagnosis and neovascularization was compared between eyes with and
      without reticular pseudodrusen. RESULTS: The mean age (+/-standard deviation) of
      the 81 patients was 74.7 +/- 6.1 years. The mean follow-up period was 27.8 +/-
      12.4 months. Fellow-eye neovascularization was noted in 31 patients (38.3%), and
      24 of these (77.4%) was a RAP subtype. Fellow-eye involvement was noted within 12
      months in 13 eyes (16.0%). The period between diagnosis and fellow-eye
      neovascularization was significantly shorter in eyes with reticular pseudodrusen
      (mean 13.8 +/- 8.5 months) than in eyes without reticular pseudodrusen (mean 21.2
      +/- 9.1 months; p = 0.031). CONCLUSION: In our cohort of unilateral RAP patients,
      fellow-eye neovascularization was noted in 38.3% in 27.8 months. The presence of
      reticular pseudodrusen in the fellow eye was closely associated with relatively
      early onset.

PMID- 25981598
TI  - Diffuse alveolar damage associated mortality in selected acute respiratory
      distress syndrome patients with open lung biopsy.
AB  - INTRODUCTION: Diffuse alveolar damage (DAD) is the pathological hallmark of acute
      respiratory distress syndrome (ARDS), however, the presence of DAD in the
      clinical criteria of ARDS patients by Berlin definition is little known. This
      study is designed to investigate the role of DAD in ARDS patients who underwent
      open lung biopsy. METHODS: We retrospectively reviewed all ARDS patients who met
      the Berlin definition and underwent open lung biopsy from January 1999 to January
      2014 in a referred medical center. DAD is characterized by hyaline membrane
      formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell
      injury. Clinical data including baseline characteristics, severity of ARDS,
      clinical and pathological diagnoses, and survival outcomes were analyzed.
      RESULTS: A total of 1838 patients with ARDS were identified and open lung
      biopsies were performed on 101 patients (5.5 %) during the study period. Of these
      101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of
      56.5 % and severe of 26.7 %. The hospital mortality rate was not significant
      difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81). Of
      the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients
      had DAD according to biopsy results. The proportion of DAD were 76.5 % (13/17) in
      mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is
      no significant difference between the three groups (p = 0.113). Pathological
      findings of DAD patients had a higher hospital mortality rate than non-DAD
      patients (71.9 % vs 45.5 %, p = 0.007). Pathological findings of DAD (odds ratio:
      3.554, 95 % CI, 1.385-9.12; p = 0.008) and Sequential Organ Failure Assessment
      score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187-1.707; p<0.001) were
      significantly and independently associated with hospital mortality. The baseline
      demographics and clinical characteristics were not significantly different
      between DAD and non-DAD patients. CONCLUSIONS: The correlation of pathological
      findings of DAD and ARDS diagnosed by Berlin definition is modest. A pathological
      finding of DAD in ARDS patients is associated with hospital mortality and there
      are no clinical characteristics that could identify DAD patients before open lung
      biopsy.

PMID- 25981601
TI  - Targeting Molecular Chaperones for the Treatment of Cystic Fibrosis: Is It a
      Viable Approach?
AB  - Cystic Fibrosis (CF) is largely caused by protein misfolding and the loss of
      function of a plasma membrane anion channel known as the cystic fibrosis
      transmembrane conductance regulator (CFTR). The most common CF-causing mutation,
      F508del, leads to severe conformational defect in CFTR. The cellular chaperone
      machinery plays an important role in CFTR biogenesis and quality control.
      Multiple attempts have been made to improve the cell surface functional
      expression of the mutant CFTR by modulating the expression of components of the
      cellular chaperone machinery. The efficacy of such an approach has been low
      largely due to the severe intrinsic folding defects of the F508del CFTR.
      Moreover, the impact of chaperone perturbation on the chaperone machinery itself
      and on other physiologically important proteins might lead to potentially severe
      side effects. Approaches aimed at disrupting chaperone-CFTR interactions show
      greater efficacy, and are compatible with small-molecule drug discovery and gene
      therapy. Combination between chaperone modulators and F508del correctors might
      further enhance potency and specificity. As molecular chaperones play important
      roles in regulating inflammation and immunity, they can be potential targets for
      controlling airway infection and inflammation in patients. If such effects can be
      synergized with chaperone-mediated regulation of CFTR biogenesis and quality
      control, more efficacious therapeutics will be developed to combat CF lung
      disease. 

PMID- 25981600
TI  - Pain perception in acute model mice of Parkinson's disease induced by 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP).
AB  - BACKGROUND: Pain is the most prominent non-motor symptom observed in patients
      with Parkinson's disease (PD). However, the mechanisms underlying the generation
      of pain in PD have not been well studied. We used a 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced mouse model of PD to analyze the relationship
      between pain sensory abnormalities and the degeneration of dopaminergic neurons.
      RESULTS: The latency to fall off the rotarod and the total distance traveled in
      round chamber were significantly reduced in MPTP-induced PD mice, consistent with
      motor dysfunction. MPTP-treated mice also showed remarkably shorter nociceptive
      response latencies compared to saline-treated mice and the subcutaneous injection
      of L-3,4-dihydroxyphenylalanine (L-DOPA) partially reversed pain hypersensitivity
      induced by MPTP treatment. We found that degeneration of cell bodies and fibers
      in the substantia nigra pars compacta and the striatum of MPTP-treated mice. In
      addition, astrocytic and microglial activation was seen in the subthalamic
      nucleus and neuronal activity was significantly increased in the striatum and
      globus pallidus. However, we did not observe any changes in neurons, astrocytes,
      and microglia of both the dorsal and ventral horns in the spinal cord after MPTP
      treatment. CONCLUSIONS: These results suggest that the dopaminergic nigrostriatal
      pathway may have a role in inhibiting noxious stimuli, and that abnormal
      inflammatory responses and neural activity in basal ganglia is correlated to pain
      processing in PD induced by MPTP treatment.

PMID- 25981602
TI  - Perspectives On Membrane-associated Progesterone Receptors As Prospective
      Therapeutic Targets.
AB  - Progesterone receptor membrane components 1 and 2, neudesin, and neuferricin
      belong to the membraneassociated progesterone receptor (MAPR) family. Recently,
      sex steroid membrane receptors have gained attention because of their potential
      involvement in sex hormone-mediated rapid non-genomic effects, which cannot
      currently be explained by the genomic action of nuclear receptors. Progesterone
      may increase cell proliferation and survival via nongenomic effects including the
      activation of the mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol 3- kinase (PI3K) pathways through MAPRs. Moreover, the
      unique expression of MAPRs suggests that they could be used as biomarkers and
      drug targets for sex steroid-related cancers and other diseases. In this review,
      we summarize the physiological roles of the MAPRs, provide a comprehensive
      overview of their progesterone-mediated non-genomic actions, and discuss new
      insights into their potential as therapeutic targets.

PMID- 25981603
TI  - ISCHEMIRs: Finding a Way Through the Obstructed Cerebral Arteries.
AB  - MicroRNAs (miRNAs) are small (19-25 nucleotides) non-coding single-stranded RNAs
      that control post-transcriptional gene expression. miRNAs are abundantly
      expressed in the brain, where they play key roles during neuronal
      differentiation, synaptogenesis, and plasticity. It is also becoming increasingly
      evident that miRNAs are involved in the etiology of several neurological
      disorders. Mounting evidence indicates that miRNAs have the ability to regulate
      the expression profiles of genes in signaling pathways associated with
      cerebrovascular diseases such as ischemic stroke, subarachnoid hemorrhage, and
      vascular dementia. For instance, miR-21 is involved in ischemic stroke pathology
      through atherosclerosis and provides neuroprotection by its anti-apoptotic
      features. miR-497 induces neuronal death and miR-210 is upregulated in hypoxic
      cells. Deregulated expression of miRNAs in response to ischemic stroke has
      enabled the use of miRNA as an efficient non-invasive biomarker. Antagomirs are
      often effective against neuronal apoptosis and can induce neuroregeneration
      following ischemia. Moreover, the advent of systems biology has introduced novel
      computational tools to identify the link between miRNAs, target genes and
      transcription factors involved in the stroke pathology and its treatment. This
      review describes the emerging role of miRNAs in neuroprotection and focuses on a
      subset of miRNAs that act as central players in ischemic stroke. 

PMID- 25981604
TI  - Liver Disease and Hepatocellular Carcinoma in Alcoholics: The Role of Anticraving
      Therapy.
AB  - Alcohol is the main risk factor for death and disability. The treatment of
      alcohol dependence (AD) is a complex activity as the variables are numerous;
      however, those which must necessarily be taken into account are the type of AD,
      the internal comorbidities and the presence of any psychiatric comorbidity. Liver
      problems are one of the most common causes of alcohol-related liver damage. 45%
      of deaths from cirrhosis are alcohol-related. Thus, the treatment of AD must
      often deal with a more or less severe liver disease, which influences the choice
      of anticraving drug. As chronic liver disease is often present, and as in a
      substantial proportion of cases, because there is a correlation with viral
      infections or with hepatocellular carcinoma (HCC), it is clear that hepatologists
      should make use of nonhepatotoxic molecules. In cases of mild liver disease, all
      available drugs might be used, but we recommend caution because the liver is
      usually fragile due to the harmful abuse of alcohol. In the advanced liver
      disease, the choice of treatment is reduced. A psychosocial approach such as
      attending support groups could be the first choice. In cases of compensated
      cirrhosis with or without HCC, or in cases of HCC without cirrhosis, metadoxine,
      acamprosate and baclofen can be used. In decompensated forms the only drug tested
      to date has been baclofen. In alcohol-related liver disease a professional team
      with hepato-alcohologists is also necessary, especially for liver transplantation
      programs. 

PMID- 25981605
TI  - Antimuscarinics in the Treatment of OAB: Is there a First-Line and a Second-Line
      Choice?
AB  - Antimuscarinics are currently the mainstay of pharmacotherapy of the overactive
      bladder (OAB) syndrome. Several meta-analyses have confirmed their efficacy in
      comparison with placebo, although the clinical significance of differences in
      parameters recorded in clinical trials has been questioned. Trials examining the
      effect of antimuscarinics on outcomes which matter to the patients, such as
      subjective cure/improvement rates, quality of life parameters and cost
      effectiveness are relatively limited. Also, comparative studies between the
      various available drugs have been designed to support the registration
      requirements and rarely provide information critical for a physician who needs to
      assess the best first-line choice for the specific patient, or even a second-line
      management. Data which might be useful for clinicians who would embark on
      tailoring the management of OAB for the individual patient could be found in
      systematic reviews/meta-analyses, cost-effectiveness studies and studies
      investigating the patients' adherence to treatment and persistence with
      pharmacotherapy for OAB. In addition, patient co-morbidities and concurrent
      treatments should be taken into consideration in conjunction with the safety
      profile of each antimuscarinic. Available evidence suggests that the use of ER
      formulations of antimuscarinics is favoured over the IR formulations when
      concerning best balance between efficacy and adverse events, cost-effectiveness,
      adherence and persistence with treatment. 

PMID- 25981606
TI  - Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or
      Finasteride?
AB  - Benign prostatic hyperplasia (BPH) is a potentially progressive disease which is
      commonly associated with bothersome lower urinary tract symptoms (LUTS) and might
      result in complications, such as acute urinary retention and BPH-related surgery.
      In the current medical therapy scenario for LUTS attributed to BPH, only one
      class of drugs, 5-alpha reductase inhibitors (5ARIs), has been found to be
      effective in reducing the risk of disease progression. The two 5ARIs that are
      currently available include finasteride and dutasteride. These two drugs have
      different pharmacokinetic and pharmacodynamic properties. Greater suppression of
      dehydrotestosterone is achieved by dutasteride (>90% dutasteride vs 70%
      finasteride) which theoretically should correlate with greater efficacy in
      alleviating urinary symptoms. Unfortunately, this hypothesis has not yet been
      clinically demonstrated. The pertinent literature is scarce and heterogeneous and
      produces low scientific levels of evidence. The present review article aims to
      evaluate the comparative head-to-head studies in order to evaluate if the
      hypothetical clinical differences between dutasteride and finasteride do exist.
      Pharmacological treatment with either drug results in similar symptom
      improvements; however dutasteride seems to have a better profile in reducing the
      risk of prostate surgery and acute urinary retention (AUR). More studies are
      necessary to better evaluate both the clinical and pharmacoeconomic profile of
      the two 5ARIs. 

PMID- 25981607
TI  - Deep Vein Thrombosis and Pulmonary Embolism in the Apixaban Era: From Bench to
      Bedside.
AB  - BACKGROUND: The traditional treatment of venous thromboembolism (VTE) with
      heparin and warfarin has numerous limitations. New oral anticoagulants represent
      the promising alternative with the potential to overcome the limitations of
      traditional treatment. OBJECTIVE: Apixaban is an oral factor Xa inhibitor with a
      rapid onset of action and predictable pharmacokinetics that allows a fixed dose
      regimen. With this characteristic apixaban overcomes many limitations and
      simplifies treatment of VTE eliminating the need for initial parenteral
      anticoagulant therapy and laboratory monitoring. RESULTS: Fixed-dose regimen of
      oral apixaban alone is as effective as conventional treatment regimen and is
      associated with a clinically relevant reduction of major bleeding. Extended
      anticoagulation with apixaban with either a treatment dose (5 mg twice daily) or
      thromboprophylactic dose (2.5 mg twice daily) reduces the risk of recurrent
      venous thromboembolism without increase in the rate of major bleeding.
      CONCLUSION: Therefore, apixaban provides a simple, effective and safe alternative
      to conventional acute or long-term treatment of VTE.

PMID- 25981608
TI  - Endogenous Retroelements in Cellular Senescence and Related Pathogenic Processes:
      Promising Drug Targets in Age-Related Diseases.
AB  - Endogenous retroelements (ERs) represent nearly half of the human genome.
      Considered up to recent years as "functionless" DNA sequences, they are now known
      to be involved in important cellular functions such as stress response and
      generation of non coding regulatory RNAs. Moreover, an increasing amount of data
      supports the idea of ERs as key players in cellular senescence and in different
      senescence-related pathogenic cellular processes, including those leading to
      inflammation, cancer and major age-related multifactorial diseases. The
      involvement of ERs in these biological mechanisms can suggest new therapeutic
      strategies in neoplasms, inflammatory/autoimmune diseases and in different age
      related pathologies, such as macular degeneration, diabetes, cardiovascular
      diseases and major age-related neurodegenerative disorders. The therapeutic
      approaches which can be suggested range from a set of well-known, common drugs
      that have been shown to modulate ERs activity, to immune therapy against ER
      derived tumor antigens, to more challenging strategies such as those based on
      anti-ERs RNA interference.

PMID- 25981609
TI  - An Integrative Review on Role and Mechanisms of Ghrelin in Stress, Anxiety and
      Depression.
AB  - Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells
      of gastric oxyntic mucosa to stimulate appetite and food intake along with
      regulation of growth hormone and insulin secretion; glucose and lipid metabolism;
      gastrointestinal motility; blood pressure, heart rate and neurogenesis.
      Furthermore, peripherally (after crossing the blood brain barrier) as well as
      centrally synthesized ghrelin (in the hypothalamus) regulates diverse functions
      of central nervous system including stress-associated behavioral functions.
      Exposure to stress alters the ghrelin levels and alteration in ghrelin levels
      significantly affects neuro-endocrinological parameters; metabolism-related
      physiology, behavior and mood. Studies have shown both anxiolytic and anxiogenic
      role of ghrelin suggesting its dual role in modulating anxiety-related behavior.
      However, it is proposed that increase in ghrelin levels during stress condition
      is an endogenous stress coping behavior and increased ghrelin levels may be
      required to prevent excessive anxiety. In preclinical and clinical studies, an
      elevation in ghrelin levels during depression has been correlated with their
      antidepressant activities. Ghrelin-induced modulation of stress and associated
      conditions has been linked to alteration in hypothalamic-pituitary-adrenal (HPA)
      axis; autonomic nervous system (mainly sympathetic nervous system and
      serotonergic neurotransmission. A reciprocal relationship has been reported
      between corticotropin-releasing hormone (CRH) and ghrelin as ghrelin increases
      the release of CRH, ACTH and corticosteroids; while CRH decreases the expression
      of ghrelin. Similarly, ghrelin increases the serotonin turnover and in turn,
      serotonin controls ghrelin signaling to modulate anxiety-related behavior. The
      present review discusses the dual role of ghrelin in stress and related
      behavioral disorders along with possible mechanisms.

PMID- 25981610
TI  - Advances in Inhibitors of FXa.
AB  - Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism
      (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for
      people's morbidity and mortality and have severely affected the people's quality
      of life all over the world. According to WHO statistics, an average of 17 million
      people are killed by the thromboembolic diseases each year globally. Therefore,
      the prevention and treatment of thromboembolic diseases have received widespread
      attention in recent years. Based on thrombotic mechanism, anti-thrombotic drugs
      are mainly divided into anticoagulants, antiplatelet agents and direct
      thrombolytic drugs. In particular, anticoagulants such as vitamin K antagonists
      (VKAs), unfractionated heparin (UFH), and low-molecular-weight heparins (LMWHs)
      have become the main therapies for pre-treatment of thromboembolic disorders.
      However, the limitations of traditional anticoagulants such as slow onset of
      action, dose-adjusted requirement, drug-drug and drug-food interactions have
      restricted their improvement in the clinical treatment. The mechanism of the
      thromboembolic disorders has indicated that coagulation factor Xa (fXa) plays a
      pivotal role in the blood coagulation cascade. Thus, selective inhibition of fXa
      by diminishing the amplified generation of thrombin without affecting the pre
      existing thrombin levels can provide better antithrombotic effect, thereby
      causing less impairment of primary hemostasis. In this paper, we mainly introduce
      the recent advances of fXa inhibitors, with focus on their biological activity
      and structure-activity relationship (SAR) information. In particular, the
      inspirations from the structures of the fXa inhibitors and their future direction
      are highlighted. 

PMID- 25981612
TI  - Long-term results of pancreaticoduodenectomy with superior mesenteric and portal
      vein resection for ductal adenocarcinoma in the head of the pancreas.
AB  - INTRODUCTION: The benefit of pancreaticoduodenectomy (PD) with superior
      mesenteric-portal vein resection (PVR) for pancreatic adenocarcinoma (PA) is
      still controversial in terms of morbidity, mortality and survival. We conducted a
      retrospective study to analyze outcomes of PD with PVR in a Spanish tertiary
      centre. METHODS: Between 2002 and 2012, 10 patients underwent PVR (PVR+ group)
      and 68 standard PD (PVR- group). Morbidity, mortality, overall survival (OS) and
      disease-free survival (DFS) were compared between PVR+ and PVR- group. Prognostic
      factors were identified by a Cox regression model. RESULTS: Postoperative
      mortality was 5% (4/78), all patients in PVR- group. Morbidity was higher in the
      PVR- group compared to PVR+ (63 vs. 30%, P=.004). OS at 3 and 5 years was 43 and
      43% in PVR+ group, 35 and 29% in PVR- group (P=.07). DFS at 3 and 5 years DFS
      were 28 and 15% in PVR+ group, 25 and 20% in PVR- group (P=.84). Median survival
      was 23.1 months in PVR- group, and 22.8 months in PVR+ group (P=.73). Factors
      related with OS were absence of adjuvant treatment (OR 2.9, 95%IC: 1.39-6.14,
      P=.003), R1 resection (OR 2.3, 95%IC: 1.2-4.43, P=.006), preoperative CA 19.9
      level >= 170 UI/mL (OR 2.3, 95%IC: 1.22-4.32, P=.01). DFS risk factors were R1
      resection (OR 2.6, 95%IC: 1.41-4.95, P=.002); moderate or poor tumor
      differentiation grade (OR 2.7, 95%IC: 1.23-6.17, P=.01); N1 lymph node status (OR
      1.8, 95%IC: 1.02-3.19, P=.04); CA 19.9 level >= 170 UI/mL (OR 2.4, 95%IC: 1.30
      4.54, P=.005). CONCLUSIONS: PVR for PA can be performed safely. Patients with PVR
      have a comparable survival to patients undergoing standard PD if disease-free
      margins can be obtained.

PMID- 25981613
TI  - Results of transanal endorrectal descent in Hirschprung's disease.
AB  - OBJECTIVE: To present our experience of patients with Hirschsprung disease (HD)
      operated by transanal endorrectal descent (TED). METHODS: A retrospective study
      performed of TEDs. We correlate fundamentally the aganglionic segment length
      with: Complications, need for colostomy and surgical approach. RESULTS: Between
      2003 and 2012 we performed 73 TED (57 men), 78.6% diagnosed in the neonatal
      period. The aganglionic segment length evidenced in the enema was correlated with
      surgical findings in 68.9% of cases, being higher in the short forms than in the
      long segments (80.9 vs. 44%, P<.001). Four patients required preoperative
      colostomy. The mean age of surgery was 6.3 months (4.5 to 33.7). Short forms
      represented 64.4% of cases. The abdominal approach was necessary in 10 patients,
      9 of these were long/total colonic aganglionic segment. Postoperative
      enterocolitis presented in 10,9% (9 patients), with no relation with the length
      of aganglionic or the existence of residual dysplasia. Obstructions occurred in
      19.2% of the long form or pancolonic forms. Currently, of the evaluable patients,
      5 present constipationand 12 present occasional leakage. CONCLUSIONS: TED is the
      surgery of choice for patients with HD. The majority can be handled by
      preoperative "nursing" without colostomy. The diagnostic tests of choice are
      manometry with suction biopsy. No significant correlation was found between
      enterocolitis and length of aganglionic segment, although we observed a drastic
      reduction of postoperative enterocolitis, since the introduction of technical
      changes, such as the use of postoperative rectal tubes and the posterior section
      of the cuff muscles.

PMID- 25981614
TI  - Emotional insecurity in the family and community and youth delinquency in
      Northern Ireland: a person-oriented analysis across five waves.
AB  - BACKGROUND: Over one billion children are exposed worldwide to political violence
      and armed conflict. Currently, conclusions about bases for adjustment problems
      are qualified by limited longitudinal research from a process-oriented, social
      ecological perspective. In this study, we examined a theoretically-based model
      for the impact of multiple levels of the social ecology (family, community) on
      adolescent delinquency. Specifically, this study explored the impact of
      children's emotional insecurity about both the family and community on youth
      delinquency in Northern Ireland. METHODS: In the context of a five-wave
      longitudinal research design, participants included 999 mother-child dyads in
      Belfast (482 boys, 517 girls), drawn from socially-deprived, ethnically
      homogenous areas that had experienced political violence. Youth ranged in age
      from 10 to 20 and were 12.18 (SD = 1.82) years old on average at Time 1.
      FINDINGS: The longitudinal analyses were conducted in hierarchical linear
      modeling (HLM), allowing for the modeling of interindividual differences in
      intraindividual change. Intraindividual trajectories of emotional insecurity
      about the family related to children's delinquency. Greater insecurity about the
      community worsened the impact of family conflict on youth's insecurity about the
      family, consistent with the notion that youth's insecurity about the community
      sensitizes them to exposure to family conflict in the home. CONCLUSIONS: The
      results suggest that ameliorating children's insecurity about family and
      community in contexts of political violence is an important goal toward improving
      adolescents' well-being, including reduced risk for delinquency.

PMID- 25981611
TI  - Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.
AB  - Intrinsic immune responses to acute leukemia are inhibited by a variety of
      mechanisms, such as aberrant antigen expression by leukemia cells, secretion of
      immunosuppressive cytokines and expression of inhibitory enzymes in the tumor
      microenvironment, expansion of immunoregulatory cells, and activation of immune
      checkpoint pathways, all leading to T cell dysfunction and/or exhaustion.
      Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to
      evade immune recognition and destruction by cytotoxic T lymphocytes. Thus,
      blockade of immune checkpoints has emerged as a highly promising approach to
      augment innate anti-tumor immunity in order to treat malignancies. Most evidence
      for the clinical efficacy of this immunotherapeutic strategy has been seen in
      patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies
      have recently revolutionized treatment of this lethal disease with otherwise
      limited treatment options. To meet the high demand for new treatment strategies
      in acute leukemia, clinical testing of these promising therapies is commencing.
      Herein, we review the biology of multiple inhibitory checkpoints (including CTLA
      4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion
      by acute leukemias. In addition, we discuss the current state of preclinical and
      clinical studies of immune checkpoint inhibition in acute leukemia, which seek to
      harness the body's own immune system to fight leukemic cells.

PMID- 25981616
TI  - Global governmentality: Biosecurity in the era of infectious diseases.
AB  - This paper uses Foucault's concept of governmentality to examine relationships
      between globalisation, the threat of infectious diseases and biosecurity. It
      draws attention to forms of calculated practices which Foucault notes as
      technologies of power that aim to foster positive demographic and economic trends
      in societies through the apparatus of security. These practices are employed at
      the global level with similar ambitions; hence, we adopt the term global
      governmentality. We discuss the applications of global governmentality by actors
      in the global core through the apparatus of security and (neo)liberal economic
      practices. We then provide examples of resistance/contestation from actors mainly
      in the global periphery through discussions of viral sovereignty; access to
      essential medicines, including HIV drugs; and health for all as a human right. We
      conclude that despite the core-periphery power asymmetry and competing paradigms,
      these developments tend to complement and/or regulate the phenomenon termed
      global governmentality, which is made evident by the tremendous successes in
      global health. 

PMID- 25981615
TI  - Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory
      responses by promoting MEKK2 ubiquitination in macrophages.
AB  - NDR/LATS kinase family is highly conserved from yeast to human. It remains
      unknown whether the members of this family function in innate immune responses.
      Here we demonstrate that Stk38 negatively regulates TLR9-mediated immune
      responses in macrophages. Stk38 constitutively associates with ubiquitin E3
      ligase Smurf1, and facilitates Smurf1-mediated MEKK2 ubiquitination and
      degradation. MEKK2 is required for CpG-induced ERK1/2 activation, TNF-alpha and
      IL-6 production but not required for LPS-induced TNF-alpha and IL-6 production.
      Accordingly, Stk38 deficiency increases CpG-induced ERK1/2 activation, TNF-alpha
      and IL-6 production without significantly affecting LPS-induced TNF-alpha and IL
      6 production. Stk38-deficient mice produce more TNF-alpha and IL-6, and display
      increased lethality than control wild-type mice upon E. coli infection. Stk38
      deficient mice are also more susceptible to CLP-induced sepsis than control mice.
      Thus, Stk38 is important in limiting inflammatory cytokine production and
      necessary for protecting host from inflammatory injury during infection, possibly
      by negatively regulating TLR9 signalling. 

PMID- 25981617
TI  - Influence of glioma cells on a new co-culture in vitro blood-brain barrier model
      for characterization and validation of permeability.
AB  - The blood-brain barrier plays an important role in protecting the brain from
      injury and diseases, but also restrains the delivery of potential therapeutic
      drugs for the treatment of brain illnesses, such as tumors. Glioma is most common
      cancer type of central nervous system in adults and the most lethal in children.
      The treatment is normally poor and ineffective. To better understand the ability
      of drug delivery systems to permeate this barrier, a blood-brain barrier model
      using human brain endothelial cells and a glioma cell line is herein proposed.
      The consistent trans-endothelial electrical values, immunofluorescence and
      scanning electronic microscopy showed a confluent endothelial cell monolayer with
      high restrictiveness. Upon inclusion of glioma cell line, the trans-endothelial
      electrical resistance decreased, with consequent increase of apparent
      permeability of fluorescein isothiocyanate dextran used as model drug, revealing
      a reduction of the barrier robustness. In addition, it was demonstrated a cell
      shape modification in the co-culture, with loss of tight junctions. The
      microenvironment of co-cultured model presented significant increase of of
      CCL2/MCP-1 and IL-6 production, correlating with the modulation of permeation.
      The results encourage the use of the proposed in vitro model as a screening tool
      when performing drugs permeability for the treatment of disorders among the
      central nervous system. 

PMID- 25981618
TI  - Evaluation of spin freezing versus conventional freezing as part of a continuous
      pharmaceutical freeze-drying concept for unit doses.
AB  - Spin-freezing as alternative freezing approach was evaluated as part of an
      innovative continuous pharmaceutical freeze-drying concept for unit doses. The
      aim of this paper was to compare the sublimation rate of spin-frozen vials versus
      traditionally frozen vials in a batch freeze-dryer, and its impact on total
      drying time. Five different formulations, each having a different dry cake
      resistance, were tested. After freezing, the traditionally frozen vials were
      placed on the shelves while the spin-frozen vials were placed in aluminum vial
      holders providing radial energy supply during drying. Different primary drying
      conditions and chamber pressures were evaluated. After 2h of primary drying, the
      amount of sublimed ice was determined in each vial. Each formulation was
      monitored in-line using NIR spectroscopy during drying to determine the
      sublimation endpoint and the influence of drying conditions upon total drying
      time. For all tested formulations and applied freeze-drying conditions, there was
      a significant higher sublimation rate in the spin-frozen vials. This can be
      explained by the larger product surface and the lower importance of product
      resistance because of the much thinner product layers in the spin frozen vials.
      The in-line NIR measurements allowed evaluating the influence of applied drying
      conditions on the drying trajectories.

PMID- 25981619
TI  - Understanding the impact of microcrystalline cellulose physicochemical properties
      on tabletability.
AB  - The quality by design (QbD) initiative is promoting a better understanding of
      excipient performance and the identification of critical material attributes
      (CMAs). Despite microcrystalline cellulose (MCC) being one of the most popular
      direct compression binders, only a few studies attempted identifying its CMAs.
      These studies were based either on a limited number of samples or on MCC produced
      on a small scale and/or in conditions that deviate from those normally
      encountered in production. The present work utilizes multivariate analyses first
      to describe a large database of MCCs produced on a commercial scale, including an
      overview of their physicochemical properties, and secondly to correlate the most
      significant material attributes with tabletability. Particle size and moisture
      content are often considered as the most common if not the sole CMAs with regard
      to MCC performance in direct compression. The evaluation of more than 80 neat
      MCCs and the performance of selected samples in a model formulation revealed the
      importance of other potential critical attributes such as tapped density. Drug
      product developers and excipient suppliers should work together to identify these
      CMAs, which may not always be captured by the certificate of analysis. 

PMID- 25981620
TI  - Prolonged survival after diagnosis of brain metastasis from breast cancer:
      contributing factors and treatment implications.
AB  - OBJECTIVE: The prognosis of breast cancer-derived brain metastasis is poor, but
      new drugs and recent therapeutic strategies have helped extend survival in
      patients. Prediction of therapeutic responses and outcomes is not yet possible,
      however. In a retrospective study, we examined prognostic factors in patients
      with breast cancer-derived brain metastasis, and we tested the prognostic utility
      of a breast cancer-specific Graded Prognostic Assessment in these patients.
      METHODS: Sixty-three patients diagnosed with brain metastasis from breast cancer
      treated surgically and adjuvantly were included. We examined clinical variables
      per primary tumor subtype: ER+/HER2- (luminal), HER2+ (human epidermal growth
      factor receptor type 2-enriched) or ER-/PR-/HER2- (triple negative). We also
      categorized patients' breast cancer-specific Graded Prognostic Assessment scores
      and analyzed post-brain metastasis survival time in relation to these categories.
      RESULTS: The breast cancers comprised the following subtypes: luminal, n = 18;
      human epidermal growth factor receptor type 2-enriched, n = 27 and triple
      negative, n = 18; median survival per subtype was 11, 37 and 3 months,
      respectively. Survival of human epidermal growth factor receptor type 2-enriched
      patients was longer, though not significantly (P = 0.188), than that of luminal
      patients. Survival of triple-negative patients was significantly short (vs. human
      epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky
      performance status, HER2 status and the disease-free interval (from initial
      treatment to first recurrence) were shown to be significant prognostic factors
      (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+:
      relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk
      1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores
      reflected disease-free intervals and survival times. CONCLUSIONS: Our data
      indicate that breast cancer-specific Graded Prognostic Assessment-based
      prediction will be helpful in determining appropriate therapeutic strategies for
      patients with brain metastasis from breast cancer.

PMID- 25981621
TI  - A multicenter retrospective analysis of sequential treatment of abiraterone
      acetate followed by docetaxel in Japanese patients with metastatic castration
      resistant prostate cancer.
AB  - OBJECTIVE: Abiraterone acetate and docetaxel are promising treatment options for
      metastatic castration-resistant prostate cancer patients. However, the optimal
      sequencing of these agents is unclear, and no previous reports discuss Japanese
      metastatic castration-resistant prostate cancer patients. The purpose of this
      analysis is to reveal the outcomes of Japanese metastatic castration-resistant
      prostate cancer patients treated with abiraterone acetate followed by docetaxel.
      METHODS: We retrospectively reviewed Japanese Phase 1 and Phase 2 trials of
      metastatic castration-resistant prostate cancer patients treated with abiraterone
      acetate until disease progression and subsequently treated with docetaxel. The
      primary outcome measure was the rates of prostate-specific antigen declines ?30
      and ?50%, respectively, with docetaxel. Secondary outcome measures included
      progression-free survival with docetaxel, and overall survival after initiation
      of abiraterone acetate and docetaxel. We performed correlation analysis between
      previous prostate-specific antigen response to abiraterone acetate and subsequent
      prostate-specific antigen response to docetaxel. RESULTS: We identified 15
      patients had experienced disease progression with abiraterone acetate and
      subsequently were treated with docetaxel. Prostate-specific antigen declines ?30
      and ?50% with docetaxel were observed in five patients (33%) and two patients
      (13%), respectively. The median progression-free survival with docetaxel was 3.7
      months (95% confidence interval: 2.9-4.6). The median overall survival from
      initiation of docetaxel and abiraterone acetate were 14.4 months (95% confidence
      interval: 6.3-22.4), and 25.7 months (95% confidence interval: 20.1-30.7),
      respectively. No significant correlation was observed between these prostate
      specific antigen responses (Pearson r = 0.206, P = 0.46). CONCLUSION: The
      efficacy of docetaxel in Japanese mCRPC patients that was resistant to
      abiraterone acetate was modest. The prostate-specific antigen response to
      previous abiraterone acetate could not predict the efficacy of subsequent
      docetaxel. Larger prospective trials are needed to validate these findings.

PMID- 25981622
TI  - One hundred supracricoid laryngectomies with cricohyoidoepiglottopexy: do we
      achieve better local control?
AB  - OBJECTIVE: Supracricoid laryngectomy with cricohyoidoepiglottopexy has been known
      to be able to cope with tumor excisions with minimal margins. Extended resection
      may result in a limited margin and may impair the prognosis. We conducted a
      clinicopathologic analysis of local recurrence in supracricoid laryngectomy with
      cricohyoidoepiglottopexy patients. METHODS: Between 1997 and 2013, 100 patients
      with glottic cancers underwent supracricoid laryngectomy with
      cricohyoidoepiglottopexy. The clinicopathologic findings were evaluated. We also
      analyzed: (i) cancer-specific and overall survival rates, (ii) the correlation
      between locoregional recurrence and overall survival, (iii) T staging and larynx
      preservation rates and (iv) previous radiation history and larynx preservation
      rates. RESULTS: Local recurrence was recognized in eight of the 100 patients
      (8%); all were initially staged as T3 or T4. Recurrence was identified in the
      submucosal regions of the ipsilateral arytenoid and/or infraglottis. Six patients
      were salvaged by completion total laryngectomy except two. Cancer-specific
      survival at 5 years was 93%; overall survival at 5 years was 89%. There was no
      significant difference between overall survival and locoregional recurrence.
      There was a significant difference between larynx preservation in T1-2 and T3-4
      patients. There was no significant difference between larynx preservation and the
      previous radiation therapy status. CONCLUSIONS: Our experience convinced us of
      the clinical potential of supracricoid laryngectomy with cricohyoidoepiglottopexy
      as one of the effective options for functional larynx preservation. Supracricoid
      laryngectomy with cricohyoidoepiglottopexy is the most suitable for unfavorable
      T2 and T3a cases and is applicable for appropriately selected radiation-failed
      patients. Thorough pre-operative evaluation, proper surgical techniques and
      careful follow-up are prerequisites for the success of supracricoid laryngectomy
      with cricohyoidoepiglottopexy.

PMID- 25981623
TI  - Evaluation of prognostic factors after radical prostatectomy in pT3b prostate
      cancer patients in Japanese population.
AB  - OBJECTIVE: The purpose of the current study was to evaluate prognostic factors
      after radical prostatectomy for prostate cancer patients with seminal vesicle
      invasion (pT3b) in the Japanese population. METHODS: Between January 2005 and
      December 2011, 814 patients underwent radical prostatectomy without neoadjuvant
      hormonal therapy at our institutions. Among these patients, 31 were (3.8%)
      presented with pT3b. Kaplan-Meier method was used to determine biochemical
      recurrence-free, disease-specific and overall survival of patients in this group.
      Proportional hazards models were used to determine predictors of biochemical
      recurrence-free survival. RESULTS: The median follow-up period was 60 months
      (range, 9-108 months). During follow-up, 23 patients (74.2%) experienced
      biochemical recurrence, and the overall 3-year probability of freedom from
      biochemical recurrence was 29%. However, only one patient died of the disease,
      and the 5-year overall survival was 92%. In multivariate analysis, age at the
      time of surgery was the only significant variable for predicting biochemical
      recurrence after radical prostatectomy (P = 0.0356, hazard ratio = 0.92, 95%
      confidence interval = 0.851-0.994). CONCLUSIONS: Patients with seminal vesicle
      invasion of pathological specimens after radical prostatectomy have high
      biochemical recurrence, but the survival was favorable especially in light of
      current multimodal treatment regimens. However, patients with younger age at the
      time of surgery, in particular, should receive multimodal treatments to improve
      their outcome.

PMID- 25981624
TI  - Motives of Dutch persons aged 50 years and older to accept vaccination: a
      qualitative study.
AB  - BACKGROUND: Elderly in several European countries are currently being vaccinated
      against influenza and pneumococcal disease, and various reasons have been put
      forward to expand these programs. To successfully immunize the older adult
      population, however, it is crucial for the target group to accept such
      interventions. This study aims to elucidate the motives of Dutch persons aged >=
      50 years for accepting vaccination. METHODS: Thirteen focus groups were composed
      with persons aged 50 years and older. A semi-structured topic list with open
      ended questions was used to guide the focus groups. The transcripts were analyzed
      according the principles of thematic survey. By an inductive process, the main
      themes and related subthemes were extracted from the responses. RESULTS: Eight
      themes were found to play an important role in accepting vaccination: healthy
      aging; usefulness of vaccination in older age; risk of getting an infectious
      disease; vaccine characteristics; severity of the disease and its implications;
      the experiences of previous vaccinations; the influence of healthcare workers and
      other people; and the need for information. CONCLUSIONS: This qualitative study
      reveals that acceptance of vaccination is not based on a single argument. The
      most important one appears to be the risk of getting an infectious disease. In
      that light, vaccination campaigns may emphasize the susceptibility of older
      adults. It is also advisable to consider the usefulness of vaccination in older
      age as an overall argument. A tailored approach to offering vaccination may be
      considered. Further research would be needed to determine the relative importance
      of the factors identified in this study.

PMID- 25981625
TI  - Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry for
      Quantitative Analysis of Glycans Labeled with Multiplex Carbonyl-Reactive Tandem
      Mass Tags.
AB  - Recently developed carbonyl-reactive aminoxy tandem mass tag (aminoxyTMT)
      reagents enable multiplexed characterization and quantitative comparison of
      structurally complex glycans between different biological samples. Compared to
      some previously reported isotopic labeling strategies for glycans, the use of the
      aminoxyTMT method features a simple labeling procedure, excellent labeling
      efficiency, and reduced spectral complexity at the MS(1) level. Presence of the
      tertiary amine functionality in the reporter region of the aminoxyTMT labels
      leads to increased ionization efficiency of the labeled glycans thus improving
      electrospray ionization (ESI)-mass spectrometry (MS) detection sensitivity. The
      use of the labeling reagent also makes electrophoretic separation of the labeled
      neutral and acidic glycans feasible. In this work, we characterized the ESI and
      collision induced dissociation (CID) behavior of the aminoxyTMT-labeled neutral
      and sialylated glycans. For the high-mannose N-glycans and small sialylated
      oligosaccharides, CID fragmentation of [M + Na + H](2+) provides the most
      informative MS(2) spectra for both quantitative and qualitative analysis. For
      complex N-glycans, MS(3) of the protonated Y1(H) ion can be used for relative
      quantification without interference from the HexNAc fragments. Online capillary
      electrophoresis (CE)-ESI-MS/MS analyses of multiplexed aminoxyTMT-labeled human
      milk oligosaccharides (HMOs) and different types of N-glycans released from
      glycoprotein standards were demonstrated. Improved resolution and quantification
      accuracy of the labeled HMO isomers was achieved by coupling CE with traveling
      wave ion mobility (TWIM)-CID-MS/MS. N-Glycans released from human serum protein
      digests were labeled with six-plex aminoxyTMT and subjected to CE-ESI-MS/pseudo
      MS(3) analysis, which demonstrated the potential utility of this glycan relative
      quantification platform for more complex biological samples. 

PMID- 25981626
TI  - Re: Kim NK, Nam W, Kim HJ. Comparison of miniplates and biodegradable plates in
      reconstruction of the mandible with a fibular free flap.

PMID- 25981627
TI  - Management and maintenance of the airway in cervical necrotising fasciitis: a
      retrospective analysis of 15 cases.
AB  - Cervical necrotising fasciitis is a progressive deep infection of the neck
      associated with high mortality, and skillful management of the airway is critical
      for operations under general anaesthesia. Tracheostomy under local anaesthesia
      has been considered the gold standard of airway management in patients with deep
      neck infections, but it may be difficult or impossible in advanced cases. We
      report here our experience over 6 years (January 2008 and December 2013) during
      which a total of 15 patients was diagnosed with cervical necrotising fasciitis.
      Of 6 patients, admitted between January 2008 and March 2010, 5 had routine
      tracheostomy under local anaesthesia, 1 had direct laryngoscopy intubation, and 9
      who were admitted between Spring 2010 and December 2013 were treated with
      nasotracheal intubation. Postoperatively all patients were given moderate
      sedation and analgesia. Nasotracheal intubation was continued until the infection
      had been controlled. During intubation patency of the endotracheal tube was
      maintained by humidification with a continuous pump of 0.45% sodium chloride and
      suction. All 15 patients (10 men and 5 women, mean age 62 years, range 36-93)
      required an emergency drainage procedure under general anaesthesia. Fourteen of
      the 15 had evidence of compromise of the airway, but emergency intervention was
      not required. Since Spring 2010, 9 consecutive patients had required nasotracheal
      intubation, including 7 video laryngoscopies and 2 fibreoptic bronchoscopies. No
      other interventions were required. Patients were intubated postoperatively from 3
      to 14 days, and there were no problems with the airway. Advanced techniques for
      control of the airway have a high rate of success in patients with necrotising
      fasciitis and could be an appropriate alternative to a traditional airway.
      Postoperative sedation and analgesia should be considered as routine management
      of pain and anxiety. 

PMID- 25981628
TI  - Red or white? Use of high colour-rendering index, light-emitting diodes in
      monitoring of free flaps of the head and neck.

PMID- 25981629
TI  - 'Emigration is a matter of self-preservation. The working conditions . . . are
      killing us slowly': qualitative insights into health professional emigration from
      Ireland.
AB  - BACKGROUND: Achieving a sustainable health workforce involves training and
      retaining sufficient staff to deliver health services. The Irish health workforce
      is characterised by a high level of emigration of Irish-trained staff and a heavy
      reliance on internationally trained staff. This paper presents qualitative
      findings from a mixed-method study of doctors, nurses and midwives who have
      recently emigrated from Ireland. METHODS: Using Facebook, this study elicited 556
      (388 completed) responses to an exploratory mixed-method online survey in July
      2014. Respondents provided rich responses to two free-text questions, one on
      health worker return (N = 343) and another on health professional emigration (N =
      209) from the source country (Ireland). RESULTS: Respondents emigrated because of
      difficult working conditions in the Irish health system (long working hours,
      uncertain career progression), which compared poorly with conditions in the
      destination country. Respondents' experiences in the destination country
      vindicated the decision to emigrate and complicated the decision to return. Their
      return to Ireland was contingent upon significant reform of the Irish health
      system and an improvement in working conditions, expressed, for example, as:
      'It's not about the money, it's about respect . . . we love working in medicine,
      but we love our families and health more' (RD283). CONCLUSIONS: This paper
      highlights that doctors, nurses and midwives are emigrating from Ireland in
      search of better working conditions, clear career progression pathways and a
      better practice environment. The question for the source country is whether it
      can retain and attract back emigrant doctors, nurses and midwives by matching
      their expectations.

PMID- 25981630
TI  - Minimum network constraint on reverse engineering to develop biological
      regulatory networks.
AB  - Reconstructing the topological structure of biological regulatory networks from
      microarray expression data or data of protein expression profiles is one of major
      tasks in systems biology. In recent years, various mathematical methods have been
      developed to meet this task. Here, based on our previously reported reverse
      engineering method, we propose a new constraint, i.e., the minimum network
      constraint, to facilitate the reconstruction of biological networks. Three well
      studied regulatory networks (the budding yeast cell cycle network, the fission
      yeast cell cycle network, and the SOS network of Escherichia coli) were used as
      the test sets to verify the performance of this method. Numerical results show
      that the biological networks prefer to use the minimal networks to fulfill their
      functional tasks, making it possible to apply minimal network criteria in the
      network reconstruction process. Two scenarios were considered in the
      reconstruction process: generating data using different initial conditions; and
      generating data from knock out and over-expression experiments. In both cases,
      network structures are revealed faithfully in a few steps using our approach. 

PMID- 25981631
TI  - A spatial-temporal transmission model and early intervention policies of 2009
      A/H1N1 influenza in South Korea.
AB  - We developed a spatial-temporal model of the 2009 A/H1N1 influenza pandemic in
      the Seoul metropolitan area (SMA), which is located in the north-west of South
      Korea and is the second-most complex metropolitan area worldwide. This multi
      patch influenza model consists of a SEIAR influenza transmission model and flow
      model between two districts. This model is based on the daily confirmed cases of
      A/H1N1 influenza collected by the Korea Center for Disease Control and Prevention
      from April 27 to September 15, 2009 and the daily commuting data from 33
      districts of SMA reported in the 2010 Population and Housing Census (PHC). We
      analyzed the spread patterns of 2009 influenza in the SMA by the reproductive
      numbers and geographic information systems. During the early period of novel
      influenza pandemics, when pharmaceutical interventions are lacking, non
      pharmaceutical public health interventions will be the most critical strategies
      for impeding the spread of influenza and delaying an epidemic. Using the spatial
      temporal model developed herein, we also investigated the impact of non
      pharmaceutical public health interventions, isolation and/or commuting
      restrictions, on the incidence reduction in various scenarios. Our model provides
      scientific evidence for predicting the spread of disease and preparedness for a
      future pandemic. 

PMID- 25981632
TI  - Cancer might be a failed response to renegade mitochondria.

PMID- 25981633
TI  - Ribosome binding site libraries and pathway modules for shikimic acid synthesis
      with Corynebacterium glutamicum.
AB  - BACKGROUND: The shikimic acid (SA) pathway is a fundamental route to synthesize
      aromatic building blocks for cell growth and metabolic processes, as well as for
      fermentative production of various aromatic compounds. Genes encoding enzymes of
      SA pathway are not continuous on genome and they are differently regulated.
      RESULTS: In this study, efforts were made to construct continuous genetic modules
      of SA pathway that are regulated by a same Ptac promoter. Firstly, aro genes
      [aroG (NCgl2098), aroB (NCgl1559), aroD (NCgl0408) and aroE (NCgl1567)] from
      Corynebacterium glutamicum and ribosome binding site (RBS) libraries that were
      tailored for the above genes were obtained, and the strength of each RBS in the 4
      libraries was quantified. Secondly, 9 genetic modules were built up from the RBS
      libraries, a previously characterized ribozyme insulator (RiboJ) and
      transcriptional promoter (Ptac) and terminator, and aroG, aroB, aroD and aroE.
      The functionality and efficiency of the constructed genetic modules were
      evaluated in C. glutamicum by determination of SA synthesis. Results showed that
      C. glutamicum RES167DeltaaroK carrying a genetic module produced 4.3 g/L of SA,
      which was 54 folds higher compared to that of strain RES167DeltaaroK (80 mg/L,
      without the genetic module) during fermentation in 250-mL flasks. The same strain
      produced 7.4, and 11.3 g/L of SA during 5-L batch and fed-batch fermentations,
      respectively, which corresponding to SA molar yields of 0.39 and 0.24 per mole
      sucrose consumption. CONCLUSION: These results demonstrated that the constructed
      SA pathway modules are effective in increasing SA synthesis in C. glutamicum, and
      they might be useful for fermentative production of aromatic compounds derived
      from SA pathway.

PMID- 25981634
TI  - Is skin autofluorescence a marker of metabolic memory in pregnant women with
      diabetes?
AB  - AIM: To determine whether skin autofluorescence can help to detect those who have
      previously had abnormal glucose levels among women referred for diabetes during
      pregnancy. METHODS: Using an advanced glycation end product reader (AGE
      Reader(tm) (;) DiagnOptics BV, Groningen, the Netherlands), we measured forearm
      skin autofluorescence at 24-30 weeks of gestation in all women who were referred
      to our Nutrition Diabetology unit for diabetes during pregnancy. RESULTS: The
      study included 230 women (200 with gestational diabetes and 30 with pre
      gestational diabetes, of whom 21 had Type 1 and nine had Type 2 diabetes) and a
      reference group of 22 normoglycaemic non-pregnant women. Skin autofluorescence
      was significantly higher in women with pre-gestational diabetes (1.97 +/- 0.44
      arbitary units) compared with gestational diabetes (1.77 +/- 0.32 arbitary units;
      P = 0.003) and lower in the reference group (1.60 +/- 0.32 arbitary units; P =
      0.009 vs all pregnant women). Among women with gestational diabetes, 71 had a
      history of hyperglycaemia (i.e. gestational diabetes or macrosomia in a previous
      pregnancy or discovery of diabetes before 24th gestational week in the present
      pregnancy). These women had higher levels of skin autofluorescence (1.83 +/- 0.35
      arbitary units) than women with gestational diabetes without previous history of
      hyperglycaemia (1.73 +/- 0.30 arbitary units; P = 0.04, non-significant, adjusted
      for age). Skin autofluorescence increased with the number of criteria present for
      previous hyperglycaemia (P for trend = 0.008) and was significantly associated
      with having two or three criteria for hyperglycaemia after adjusting for age (P =
      0.02). CONCLUSIONS: Skin autofluorescence could reflect previous long-term
      hyperglycaemia in pregnant women, and could therefore be a marker of metabolic
      memory.

PMID- 25981635
TI  - 18F-fluorodeoxyglucose positron emission tomography for predicting tumor response
      to radiochemotherapy in nasopharyngeal carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the value of (18)F
      fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting tumor
      response to radiochemotherapy in nasopharyngeal carcinoma (NPC). MATERIALS AND
      METHODS: From July 2012 to March 2014, 46 NPC patients who had undergone PET
      scanning before receiving definitive intensity-modulated radiotherapy (IMRT)
      treatment in our hospital were enrolled. Factors potentially affecting tumor
      response to treatment were studied by multiple logistic regression analysis.
      RESULTS: After radiochemotherapy, 32 patients had a clinical complete response
      (CR), making the CR rate 69.6%. Multiple logistic regression analysis
      demonstrated that the maximal standard uptake value (SUV max) of the primary
      tumor was the only factor related to tumor response (p = 0.001), and that the
      logistic model had a high positive predictive value (90.6%). The area under the
      receiver operating characteristic (ROC) curve was 0.809, with a best cutoff
      threshold at 10.05. Patients with SUV max <= 10 had a higher CR rate than those
      with SUV max > 10 (p < 0.001). CONCLUSION: The SUV max of the primary tumor
      before treatment is an independent predictor of tumor response in NPC.

PMID- 25981636
TI  - Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two
      Children with X-CGD - Importance of Timing.
AB  - We report on a series of sequential events leading to long-term survival and cure
      of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma
      retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life
      threatening infections requiring hematopoietic stem cell transplantation (HSCT)
      but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following
      GT both children completely resolved invasive Aspergillus nidulans infections.
      However, one child developed dual insertional activation of ecotropic viral
      integration site 1 (EVI1) and signal transducer and activator of transcription 3
      (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite
      resistance to mismatched allo-HSCT with standard myeloablative conditioning,
      secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and
      disappearance of MDS. The other child did not develop MDS despite expansion of a
      clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and
      was cured by early standard allo-HSCT. The slowly developing dominance of clones
      harboring integrations in MDS1-EVI1 may guide clinical intervention strategies,
      i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential
      for both children to survive and to clear therapy-refractory infections, and
      future GT with safer lentiviral self-inactivated (SIN) vectors may offer a
      therapeutic alternative for X-CGD patients suffering from life-threatening
      infections and lacking HLA-identical HSC donors. 

PMID- 25981637
TI  - Gene Manipulation of Human Embryonic Stem Cells by In Vitro-Synthesized mRNA for
      Gene Therapy.
AB  - The difficulty in producing genetically modified human embryonic stem cells
      (hESCs) limits research on their applications. Virus-based gene transfer is not
      safe for clinical use, whereas DNAbased non-viral methods are not efficient or
      safe, and mRNA-based methods are useful for genetic manipulation. In this study,
      we easily obtained multiple types and large amounts of in vitro-synthesized mRNA
      by PCR. The efficiency of different transfection methods was studied by flow
      cytometry. The effect of different mRNA modifications on protein translation
      efficiency and dynamics of luciferase mRNA expression in hESCs were studied using
      a bioluminescence imaging system. The pluripotency of hESCs after transfection
      was studied by immunofluorescence. In vitro-synthesized pancreatic-duodenal
      homeobox 1 (PDX1) mRNA was used to induce the differentiation of hESCs into
      insulin-producing cells. We found that electroporation is the most efficient
      transfection method, and it produces more than 95% transgene expression in
      multiple hESC lines. Synthesized mRNA with a combination of a polyA tail, cap and
      base analogues is more efficiently translated into protein in hESCs compared with
      single-modified mRNA. Transfection of mRNA into hESCs by trypsinizing the cells
      into single-cell suspensions did not affect their pluripotency, and multiple
      types of mRNAs can be transfected into hESCs efficiently. We found that PDX-1
      mRNA transfection significantly improved the expression level of genes related to
      beta cells and differentiated cells that express insulin and C-peptide. ELISA
      analysis validate the insulin secretion of islet-like cell clusters in response
      to glucose stimulation. Our results indicate that electroporation of in vitro
      synthesized mRNA is useful for genetic manipulation of hESCs and differentiation
      of hESCs into particular cell types, and this finding will pave the way for
      clinical applications of this method. 

PMID- 25981638
TI  - Development of customized positioning guides using computer-aided design and
      manufacturing technology for orthognathic surgery.
AB  - PURPOSE: The purpose of this study was to devise a method for producing
      customized positioning guides for translating virtual plans to actual
      orthognathic surgery, and evaluation of the feasibility and validity of the
      devised method. METHODS: Patients requiring two-jaw orthognathic surgery were
      enrolled and consented before operation. Two types of positioning guides were
      designed and fabricated using computer-aided design and manufacturing technology:
      One of the guides was used for the LeFort I osteotomy, and the other guide was
      used for positioning the maxillomandibular complex. The guides were fixed to the
      medial side of maxilla. For validation, the simulation images and postoperative
      cone beam computed tomography images were superimposed using surface registration
      to quantify the difference between the images. The data were presented in root
      mean-square difference (RMSD) values. RESULTS: Both sets of guides were
      experienced to provide ideal fit and maximal contact to the maxillary surface to
      facilitate their accurate management in clinical applications. The validation
      results indicated that RMSD values between the images ranged from 0.18 to 0.33 mm
      in the maxilla and from 0.99 to 1.56 mm in the mandible. The patients were
      followed up for 6 months or more, and all of them were satisfied with the
      results. CONCLUSION: The proposed customized positioning guides are practical and
      reliable for translation of virtual plans to actual surgery. Furthermore, these
      guides improved the efficiency and outcome of surgery. This approach is
      uncomplicated in design, cost-effective in fabrication, and particularly
      convenient to use.

PMID- 25981641
TI  - A note on the full-neighborhood search of Kaandorp and Koole (2007).
AB  - We give an efficient method for enumerating Kaandorp and Koole's (2007; Health
      Care Mgmt Sci 10:217-229) "full neighborhood" of candidate improvement schedules
      employed by their algorithm's local search for the optimal outpatient appointment
      schedule. A proposition is given that the first appointment interval is always
      used in the optimal schedule; this allows convenient indexing within our method. 

PMID- 25981640
TI  - Urban health indicators and indices--current status.
AB  - Though numbers alone may be insufficient to capture the nuances of population
      health, they provide a common language of appraisal and furnish clear evidence of
      disparities and inequalities. Over the past 30 years, facilitated by high speed
      computing and electronics, considerable investment has been made in the
      collection and analysis of urban health indicators, environmental indicators, and
      methods for their amalgamation. Much of this work has been characterized by a
      perceived need for a standard set of indicators. We used publication databases
      (e.g. Medline) and web searches to identify compilations of health indicators and
      health metrics. We found 14 long-term large-area compilations of health
      indicators and determinants and seven compilations of environmental health
      indicators, comprising hundreds of metrics. Despite the plethora of indicators,
      these compilations have striking similarities in the domains from which the
      indicators are drawn--an unappreciated concordance among the major collections.
      Research with these databases and other sources has produced a small number of
      composite indices, and a number of methods for the amalgamation of indicators and
      the demonstration of disparities. These indices have been primarily used for
      large-area (nation, region, state) comparisons, with both developing and
      developed countries, often for purposes of ranking. Small area indices have been
      less explored, in part perhaps because of the vagaries of data availability, and
      because idiosyncratic local conditions require flexible approaches as opposed to
      a fixed format. One result has been advances in the ability to compare large
      areas, but with a concomitant deficiency in tools for public health workers to
      assess the status of local health and health disparities. Large area assessments
      are important, but the need for small area action requires a greater focus on
      local information and analysis, emphasizing method over prespecified content.

PMID- 25981639
TI  - The glutamate transport inhibitor DL-Threo-beta-Benzyloxyaspartic acid (DL-TBOA)
      differentially affects SN38- and oxaliplatin-induced death of drug-resistant
      colorectal cancer cells.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death globally
      and new biomarkers and treatments are severely needed. METHODS: Here, we employed
      HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to
      investigate whether altered expression of the high affinity glutamate
      transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with
      the resistant phenotypes. Analyses included real-time quantitative PCR,
      immunoblotting and immunofluorescence analyses, radioactive tracer flux
      measurements, and biochemical analyses of cell viability and glutathione content.
      Results were evaluated using one- and two-way ANOVA and Students two-tailed t
      test, as relevant. RESULTS: In SN38-resistant HCT116 and LoVo cells, SLC1A1
      expression was down-regulated ~60 % and up-regulated ~4-fold, respectively, at
      both mRNA and protein level, whereas SLC1A3 protein was undetectable. The changes
      in SLC1A1 expression were accompanied by parallel changes in DL-Threo-beta
      Benzyloxyaspartic acid (TBOA)-sensitive, UCPH101-insensitive [(3)H]-D-Aspartate
      uptake, consistent with increased activity of SLC1A1 (or other family members),
      yet not of SLC1A3. DL-TBOA co-treatment concentration-dependently augmented loss
      of cell viability induced by SN38, while strongly counteracting that induced by
      oxaliplatin, in both HCT116 and LoVo cells. This reflected neither altered
      expression of the oxaliplatin transporter Cu(2+)-transporter-1 (CTR1), nor
      changes in cellular reduced glutathione (GSH), although HCT116 cell resistance
      per se correlated with increased cellular GSH. DL-TBOA did not significantly
      alter cellular levels of p21, cleaved PARP-1, or phospho-Retinoblastoma protein,
      yet altered SLC1A1 subcellular localization, and reduced chemotherapy-induced p53
      induction. CONCLUSIONS: SLC1A1 expression and glutamate transporter activity are
      altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate
      transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and
      augments CRC cell death induced by SN38, while attenuating that induced by
      oxaliplatin. These findings may point to novel treatment options in treatment
      resistant CRC.

PMID- 25981643
TI  - Preparation of longitudinal sections of hair samples for the analysis of cocaine
      by MALDI-MS/MS and TOF-SIMS imaging.
AB  - Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI)
      for the analysis of intact hair is a powerful tool for the detection of drugs of
      abuse in toxicology and forensic applications. Here we present a quick, easy, and
      reproducible method of preparing longitudinal sections of single hairs. This
      method improves the accessibility of chemicals embedded in the hair matrix for
      molecular imaging with mass spectrometry. The images obtained from a single,
      sectioned hair sample show molecular distributions in the exposed medulla,
      cortex, and a portion of the cuticle observed as a narrow layer surrounding the
      cortex. Using MALDI-MS/MS imaging, the distribution of cocaine was observed
      throughout five longitudinally sectioned drug-user hair samples. The images
      showed the distribution of the product ion at m/z 182, derived from the precursor
      ion of cocaine at m/z 304. MetA-SIMS images of longitudinally sectioned hair
      samples showed a more detailed distribution of cocaine at m/z 304,
      benzoylecgonine the major metabolite of cocaine at m/z 290 and other drugs such
      as methadone which was observed at m/z 310. Chronological information of drug
      intake can be obtained more sensitively. The chronological detail is in hours
      rather than months, which is of great interest in clinical as well as forensic
      applications.

PMID- 25981642
TI  - A mixed method feasibility study of a patient- and family-centred advance care
      planning intervention for cancer patients.
AB  - BACKGROUND: Advance care planning (ACP) is a process whereby values and goals are
      sensitively explored and documented to uphold patients' wishes should they become
      incompetent to make decisions in the future. Evidenced-based, effective
      approaches are needed. This study sought to assess the feasibility and
      acceptability of an ACP intervention informed by phase 1 findings and assessed
      the suitability of measures for a phase 3 trial. METHODS: Prospective,
      longitudinal, mixed methods study with convenience sampling. A skilled
      facilitator conducted an ACP intervention with stage III/IV cancer patients and
      invited caregivers. It incorporated the vignette technique and optional
      completion/integration of ACP documents into electronic medical records (EMR).
      Quantitative and qualitative data were collected concurrently, analysed
      separately, and the two sets of findings converged. RESULTS: Forty-seven percent
      consent rate with 30 patients and 26 caregivers completing the intervention.
      Ninety percent of patient participants had not or probably not written future
      care plans. Compliance with assessments was high and missing responses to items
      low. Small- to medium-sized changes were observed on a number of patients and
      caregiver completed measures, but confidence intervals were typically wide and
      most included zero. An increase in distress was reported; however, all believed
      the intervention should be made available. Eleven documents from nine patients
      were incorporated into EMR. ACP may not be furthered because of intervention
      inadequacies, busy lives, and reluctance to plan ahead. CONCLUSIONS: In this
      phase 2 study we demonstrated feasibility of recruitment and acceptability of the
      ACP intervention and most outcome measures. However, patient/family preferences
      about when and whether to document ACP components need to be respected. Thus
      flexibility to accommodate variability in intervention delivery, tailored to
      individual patient/family preferences, may be required for phase 3 research.

PMID- 25981644
TI  - [Leanness, obesity, and breast cancer risk-different impact of body weight on
      breast cancer risk according to women's life stages].
AB  - Numerous epidemiological studies, although not all, in Western countries have
      reported a possible differential impact of BMI on breast cancer risk in women of
      various lifestages. Among premenopausal women, a number of epidemiological
      studies in Western populations suggested a weak inverse association between BMI
      and breast cancer risk. Conversely, there exists substantial evidence for a
      statistically significant positive association between body weight and breast
      cancer risk among postmenopausal women. The cumulative exposure to estrogen
      throughout a woman's life is one of the significant risk factors for breast
      cancer. After menopause, adipose tissue is a major source of estrogen. Therefore,
      an increase in body fat after menopause is one of the possible explanations for
      the positive association of body weight with the development of breast cancer. To
      evaluate the impact of body weight on the risk of breast cancer, we need to
      consider the role of adipose tissue in the development and differentiation of
      normal mammary glands. Special attention should be paid to women in their
      twenties and/or during their lactation periods when the development of normal
      mammary glands is significant. Further studies are needed to investigate the
      association between BMI and breast cancer risk, considering the role of body fat
      in the development of mammary glands. 

PMID- 25981645
TI  - [Helicobacter pylori infection and Hyperglycemia/Diabetes are associated with an
      increased risk of Gastric Cancer].
AB  - Although mortality rates owing to gastric cancer have gradually decreased, the
      morbidity rates are still high in Japan. Helicobacter pylori(H. pylori)infection
      is an important risk factor for gastric cancer, although most individuals with an
      H. pylori infection do not develop this malignancy. Therefore, it is speculated
      that other risk factors including lifestyle contribute to the enhanced risk of
      gastric cancer posed by H. pylori infection. It is also noteworthy that the
      prevalence of prediabetes and diabetes has dramatically increased in Japan, and
      cancer is now considered a possible complication of the latter. However, there
      have been very few epidemiological studies evaluating the relationship between
      diabetes and gastric cancer in Japan. The Hisayama Study, which is a prospective
      cohort study conducted in a Japanese community, demonstrated that the incidence
      of gastric cancer significantly increased with elevated fasting plasma glucose
      levels. A modest increase in hemoglobin A1c levels was also a significant risk
      factor for gastric cancer even after adjusting for other risk factors, including
      H. pylori infection. Moreover, among subjects who had both a high hemoglobin A1c
      level and H. pylori infection, the risk of gastric cancer increased
      synergistically. These findings suggest that even prediabetic hyperglycemia is a
      significant risk factor for gastric cancer in the general Japanese population.
      Early identification of hyperglycemia and an appropriate behavioral and
      therapeutic approach may help prevent gastric cancer in Japan where there is a
      high incidence of both this malignancy and diabetes.

PMID- 25981646
TI  - [Chemoprevention of colorectal cancer for broad clinical use in the future].
AB  - Establishment of preemptive medicine might be useful against the growing burden
      among colorectal cancer patients. Currently, we are trying to develop effective
      chemopreventive drugs not only for improving public health(i e, cancer morbidity
      and mortality), but also for better health economics and medical services. We
      have evaluated the suppressive effects of aspirin in subjects with a moderate-to
      high risk of developing colorectal cancer through a randomized-controlled trial.
      For the first time, the efficacy of aspirin has been shown in Asian patients with
      adenomatous polyposis and recurrent colorectal tumors after endoscopic
      polypectomy. In this manuscript, we would like to show a good example of drug
      repositioning in cancer-preventive clinical trials and to discuss the future use
      of cancer-preventive agents. 

PMID- 25981647
TI  - [Prostate cancer prevention].
AB  - Environmental factors, mainly diet, play an important role in the development of
      prostate cancer. A previous study identified fat and calcium as risk factors, and
      lycopene, selenium, soy isoflavone, and vitamin E as preventive factors for the
      development of prostate cancer. However, many previous studies were observational
      or in vitro/in vivo based, and enough evidence in a large-scale randomized study
      has not been provided. In the study of food, not only the intake but also the
      metabolism is important. For soy isoflavone, analysis of enterobacterial flora
      concerned with its metabolism to equol is in progress. 

PMID- 25981648
TI  - [Genome-cohort studies for the development of personalized cancer prevention
      programs in Japan].
AB  - One of the most important roles of molecular epidemiology is to investigate gene
      environment interactions in order to provide data for personalized risk
      modification. A case-control study conducted in Aichi showed that an aldehyde
      dehydrogenase- 2(ALDH2)polymorphism together with cigarette smoking significantly
      affects the risk of lung cancer. The main purpose of this large-scale genome
      cohort study of healthy individuals is to confirm that these factors are
      associated with the development of diseases and to set optimal thresholds for the
      environmental factors. The Japan Multi-Institutional Collaborative Cohort(J
      MICC)Study was launched in 2005. It has recruited 100,600 healthy participants up
      to the end of 2014, and plans to follow them until 2025. Although Japanese genome
      cohort studies, including the J-MICC Study, the Japan Public Health Center-based
      Prospective(JPHC)Study, and the Tohoku Medical Megabank Organization Study,
      consist of different research teams with different financial resources,
      collaboration to standardize the data collection format for successful pooled
      analysis is being discussed. 

PMID- 25981649
TI  - [Indication of alternate-day treatment with S-1 in patients with oral cancer].
AB  - The recommended S-1 chemotherapy schedule for head and neck cancer is daily
      treatment for 4 weeks, followed by 2 weeks of rest. However, this can lead to
      adverse events and sometimes treatment withdrawal. Alternate-day treatment with a
      pyrimidine anticancer agent is reported to reduce adverse events without
      compromising anticancer activity. We examined the indication of alternate-day
      treatment with S-1 for oral cancer. Fifteen patients(3 men and 12 women; average
      age: 81.3 years)with oral squamous cell carcinoma started consecutive-day
      treatment with S-1. Treatment had to be interrupted after 0.5-10 courses because
      of grade >2 myelosuppression, hepatorenal and electrolyte disorder, and grade 1
      digestive toxicity. After a recovery period of 8-168 days from adverse events,
      alternate-day treatment with S-1 was started. Adverse events on this regimen were
      grade 2 leucopenia and hyperbilirubinemia in some patients. It was possible for
      10 of the patients to continue this treatment for longer than 1 year or until
      death, but 5 patients could not continue because of a recurrence of a renal or
      electrolyte disorder, pneumonia, or disease progression. It is thought that
      alternate-day treatment with S-1 reduces the incidence of adverse events compared
      to consecutive-day treatment, and can allow continuous administration.
      Alternateday treatment with S-1 for female patients aged over 80 years with grade
      1 leucopenia and/or thrombocytopenia before administration may help to maintain
      their quality of life. 

PMID- 25981650
TI  - [Adjuvant hormonal treatment for estrogen receptor-positive breast cancer-a
      questionnaire survey conducted by Japanese breast cancer society-authorized
      facilities in Hokkaido].
AB  - According to the Japanese Breast Cancer Society national breast cancer
      registration, 71.8%of breast cancer cases reported in 2004 and 79.8% of cases
      reported in 2010 were estrogen receptor(ER)positive. The frequency of ER-positive
      breast cancer is increasing annually in Japan. Many clinical trials have proven
      that adjuvant hormonal treatment affects both progression- free survival and
      overall survival in ER-positive breast cancer cases. However, some clinical
      questions remain, including those regarding the definition of preoperative
      hormonal treatment, appropriate dosage period, and therapeutic drug choice. In
      January 2013, we conducted a questionnaire survey of 53 medical doctors engaged
      in breast cancer treatment at 15 Japanese Breast Cancer Society-authorized
      facilities in Hokkaido. This survey included 6 clinical questions about
      preoperative hormonal treatment, 5 clinical questions about postoperative
      hormonal treatment for premenopausal breast cancer, and 4 clinical questions
      about postoperative hormonal treatment for postmenopausal breast cancer. We
      obtained replies from 35 medical doctors at 27 facilities. The response rate was
      66%. We accumulated and analyzed these data. The discussion of questionnaire
      results in the medical administration field facilitates the sharing of
      information regarding differences in the approaches of different facilities to
      breast cancer patients. As a result, standardization of the breast cancer medical
      treatment system in this area has been accomplished. 

PMID- 25981651
TI  - [Hange-Shashin-to for preventing diarrhea during afatinib therapy].
AB  - Afatinib is an epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR
      TKI). In a randomized phase III study(Lux- Lung 3 study)employing patients
      harboring EGFR mutations, patients administered afatinib show a significantly
      longer progression free survival time(PFS)than those administeredcombination
      chemotherapy comprising cisplatin andpemetrexed . However, most of the
      patients(95.2%)treatedwith afatinib experiencedd iarrhea. In the present report,
      16 patients with EGFR mutations were treatedby afatinib at our institution from
      May 2014 to December 2014. Twelve patients were administered a diarrhea
      prevention herbal medicine, Hange-shashin-to. Seven of 12 patients(58%)had no
      diarrhea during the 28 days of therapy. All 4 of the patients who did not receive
      Hange-shashin-to experienced diarrhea above Grade 1 within 6 days of starting
      therapy. The rate of diarrhea differed significantly between the patients
      receiving and not receiving Hangeshashin- to. In conclusion, preventive
      administration of Hange-shashin-to may reduce the occurrence of diarrhea during
      afatinib treatment. 

PMID- 25981652
TI  - [Examination of UGT1A1 polymorphisms and irinotecan-induced neutropenia in
      patients with Colorectal cancer].
AB  - Irinotecan is an effective drug in the treatment of colorectal cancer. However,
      there are reports of an association between certain UGT1A1 genetic polymorphisms
      and the development of adverse reactions(such as neutropenia)related to
      irinotecan metabolism. We retrospectively investigated UGT1A1 genetic
      polymorphisms and the occurrences of irinotecan-induced neutropenia in 25
      patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic
      polymorphisms in these patients yielded the following classifications: a wild
      type group( *1/*1)comprising 13 patients(52%), a heterozygous group(*1/ *28,
      *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2
      patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group,
      30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4
      neutropenia only occurred in the homozygous group. These results suggest that a
      dose reduction of irinotecan should be considered for patients who fall into the
      homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such
      patients might be susceptible to grade 4 neutropenia. 

PMID- 25981653
TI  - [Risk factors for predicting severe leukopenia induced by docetaxel plus
      prednisolone in patients with Castration-Resistant Prostate cancer].
AB  - The purpose of this study was to extract the risk factors for GradeB3 leukopenia
      induced by docetaxel plus prednisolone (DP)therapy administered to patients with
      castration-resistant prostate cancer. Rates of 59% for GradeB3 leukopenia and 11%
      for FN were observed. On multivariate analysis, the pretreatment white blood cell
      count(OR=0.502, 95%CI: 0.292- 0.862, p=0.01)was significantly associated with
      severe leukopenia induced by DP therapy. In addition, on univariate analysis, the
      pretreatment platelet count, disease extent, and bilirubin level were significant
      factors. We consider it necessary to immediately treat patients with these risks
      with G-CSF. 

PMID- 25981654
TI  - [Characteristics of and risk factors for interstitial pneumonia due to TS-1(R)
      capsule administration-case reviews from a drug use results survey on Non-Small
      Cell Lung cancer patients and spontaneous reports].
AB  - A drug use results survey for the TS-1(R)capsule was conducted on patients with
      non-small cell lung cancer. A total of 1,784 patients were registered for the
      survey, 1,669 of whomwere evaluated for safety. The incidence of adverse drug
      reactions was 67.9%(1,134/1,669). The overall incidence of interstitial pneumonia
      was 1.38%(23/1,669), while it was 1.34% in patients treated with TS-1(R)
      alone(14/1,046). The risk factors for interstitial pneumonia according to this
      survey included allergic predisposition, concomitant diseases(including
      interstitial pneumonia), past medical history(including interstitial pneumonia),
      and combination with anticancer drugs(excluding cisplatin). Among the spontaneous
      reports of interstitial pneumonia as an adverse drug reaction from physicians,
      test images were available in 39 cases. These images were analyzed by the Safety
      Review Committee for interstitial pneumonia, consisting of external medical
      experts. In addition, the imaging patterns, settings of occurrence, and patient's
      backgrounds were reviewed. Twenty-five of the 39 cases were assessed to be
      possible interstitial pneumonia, of which 10 were confirmed to have an imaging
      pattern of diffuse alveolar damage. Based on the above findings, it is essential
      to check the patient's medical history for conditions such as lung disorder
      through a medical interview and an imaging test, prior to starting treatment with
      TS-1(R). 

PMID- 25981655
TI  - [Successful treatment of relapsed and refractory multiple myeloma by using
      clarithromycin-lenalidomide, low-dose dexamethasone(BiRd), and melphalan
      prednisolone(MP)].
AB  - The development of novel agents has markedly improved the prognosis of multiple
      myeloma(MM). However, salvage therapies for patients with MM that is refractory
      to novel agents and conventional chemotherapies have not been established.
      Herein, we describe successful treatments for such patients with the combination
      of clarithromycin, lenalidomide, and lowdose dexamethasone(BiRd)with or without
      melphalan and prednisolone(MP). Although its duration was relatively short, the
      remission is important in terms of the salvage strategy until the second
      generation of novel agents becomes available. 

PMID- 25981656
TI  - [Successful treatment of high-dose methotrexate-induced oliguric acute renal
      failure by using a combination of hemodialysis filtration and direct
      hemoperfusion].
AB  - A 64-year-old man with central nervous system metastases from systemic non
      Hodgkin lymphoma was treated with high- dose intravenous methotrexate(MTX 3.5
      g/m2). The patient subsequently developed oliguric acute renal failure 12 hours
      after MTX initiation, and his serum MTX level was 163 mM at 26 hours.
      Hemodialysis filtration(HDF)combined with direct hemoperfusion(DHP)was initiated
      at 45hours. Seven sessions of combined HDF and DHP and 2 courses of HDF alone
      were performed, and the mean MTX extraction rates were 68.2% and 74.3%,
      respectively. The patient experienced severe respiratory failure, febrile
      neutropenia, myelosuppression, and oral mucositis. However, his urine output
      began to improve on day 7 after MTX initiation, and his renal function gradually
      recovered. His serum MTX level declined to 0.04 mM on day 23 after MTX
      initiation. In the present case, we immediately initiated HDF and DHP and
      successfully treated the patient for MTX-induced renal failure. 

PMID- 25981657
TI  - [A case of primary testicular diffuse large B-cell lymphoma with a p53 gene point
      mutation].
AB  - A 52-year-old man with bilateral swelling in the scrotum was referred to the
      department of urology in our hospital in January 2013. Pathological examination
      of the scrotum revealed diffuse large B-cell lymphoma(DLBCL). Immunohistochemical
      staining revealed p53 overexpression, and polymerase chain reaction-single strand
      conformation polymorphism(PCRSSCP) revealed a point mutation in exon 7 of the p53
      gene. Rituximab plus cyclophosphamide, doxorubicin hydrochloride, vincristine,
      and prednisolone(R-CHOP)therapy and intrathecal prophylaxis were initiated. After
      three courses of R-CHOP therapy, high-dose cytarabine was administered, followed
      by peripheral blood stem cell harvesting. Busulfan, etoposide, and Ara
      C(BEA)therapy was then administered, followed by autologous peripheral blood stem
      cell transplantation(auto- PBSCT). Primary testicular lymphoma(PTL)is a rare,
      clinically aggressive form of extranodal lymphoma, and there is a high incidence
      rate of relapse in the central nervous system(CNS). The vast majority of cases
      are histologically DLBCL. The p53 mutation is an independent marker of poor
      prognosis in patients with DLBCL treated with R-CHOP therapy. Our patient has
      been disease free for 17 months after auto-PBSCT with high-dose chemotherapy,
      which results in a greater level of penetration into the CNS. 

PMID- 25981658
TI  - [A case of Paclitaxel-induced peripheral neuropathy successfully treated with
      duloxetine].
AB  - Here, we report about a 60-year-old woman with metastatic breast cancer who was
      successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine.
      She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was
      ultimately discontinued because of grade 3 peripheral neuropathy detected on day
      15, according to the CTCAE (v4.0). She was administered duloxetine on day 90
      after the end of the previous therapy because of the peripheral neuropathy.
      Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX
      administration on her request. Further trials are required to confirm the
      efficacy of duloxetine. 

PMID- 25981659
TI  - [A case of lung cancer with small intestine metastasis with perforative
      peritonitis as the initial symptom].
AB  - Herein, we report a case oflung cancer with metastasis to the small intestine,
      with perforative peritonitis as the initial symptom. An 82-year-old man who had
      undergone subtotal gastrectomy and Roux-en-Y anastomosis for gastric cancer 8
      years previously was admitted to our hospital with abdominal pain. We diagnosed
      the patient with gastrointestinal perforation, and a chest computed
      tomography(CT)scan showed a mass in the right lung. A laparotomy revealed a 4*3
      cm sized intestinal tumor and intestinal perforation in the immediate vicinity
      ofthe anastomotic site. Segmentectomy ofthe small intestine was performed.
      Histological examination indicated that the tumor specimen was squamous cell
      carcinoma. Four months later, an abdominal CT scan showed multiple liver
      metastases, and the patient died 6 months after the operation because ofcachexia.
      At autopsy, a diagnosis ofsmall intestine metastatic tumor originating from
      squamous cell carcinoma of the lung was made. Although small intestine metastasis
      from lung cancer is rare, it should be considered when progressive abdominal
      symptoms are observed. 

PMID- 25981660
TI  - [Six-year survival with recurrent intrahepatic cholangiocarcinoma achieved by
      simple S-1 administration].
AB  - We report here a rare case of a patient with recurrent intrahepatic
      cholangiocarcinoma that was treated with simple S-1 chemotherapy, who is still
      alive 6 years later. A liver tumor was identified in segments 5 to 6 in a 60-year
      old male asymptomatic hepatitis B carrier. The tumor was diagnosed as
      hepatocellular carcinoma by MRI and CT. However, following its resection by
      extended posterior segmentectomy of the liver, pathological findings identified
      it as an intrahepatic cholangiocarcinoma. The surgical margin was cancer
      negative. No additional adjuvant chemotherapy was administered because of the
      patient 's impaired renal function. When tumor recurrence was found by MRI 30
      months later, an additional liver resection was planned but a laparotomy was
      eventually performed. This was because intraoperative findings revealed
      Glissonian sheath invasion with involvement of the umbilical portion. S-1
      treatment(100mg/body/day)was started. Although the dose had to be reduced(mostly
      75mg/body/day)due to hyperbilirubinemia and there were some interruptions in the
      regimen, in total of 42 g of S-1 was administered. The patient is currently still
      alive, 6 years after the detection of the tumor recurrence. This represents a
      rare case in patients with intrahepatic cholangiocarcinoma. 

PMID- 25981661
TI  - [Two cases of pancreatic cancer treated with FOLFIRINOX regimen and G-CSF
      prophylaxis at the standard therapeutic dose].
AB  - Recently, novel therapeutic regimens, such as FOLFIRINOX, have been demonstrated
      to show promising anti-cancer activity and to be superior to single-agent
      gemcitabine for unresectable pancreatic cancer patients with good performance
      status. In this study, we report 2 cases of pancreatic cancer treated with
      FOLFIRINOX and G-CSF prophylaxis at the standard therapeutic dose, after
      treatment with gemcitabine and S-1 chemotherapy failed. It has been reported that
      grade 3-4 neutropenia frequently occurs in patients treated with the FOLFIRINOX
      regimen. Furthermore, granulocyte colony-stimulating factor(G-CSF) has not been
      recommended for helping with neutropenia in pancreatic cancer patients treated
      with FOLFIRINOX: however, prophylactic use of G-CSF is recommended for cancer
      patients who are at high risk of neutropenic events. On the other hand, modified
      FOLFIRINOX(no bolus 5-FU)has demonstrated an improved safety profile with
      maintained efficacy, and further randomized studies to compare the overall
      survivals of the modified FOLFIRINOX versus FOLFIRINOX regimen and G-CSF
      prophylaxis are hence needed in the future.

PMID- 25981662
TI  - [A case of stage IV b pancreatic head cancer that was resected because of a good
      response to chemotherapy].
AB  - The prognosis of Stage IV b pancreatic cancer is extremely poor; the mean
      survival time is 2-4 months. However, new anticancer agents can improve the
      outcome of advanced pancreatic cancer. We present the case of a 50-year-old
      female patient with Stage IV b pancreatic head cancer with invasion to the
      superior mesenteric vein(SMV)and multiple liver metastases. The patient received
      S-1 as first-line chemotherapy. Three months later, a further CT scan showed
      reduction of the pancreatic tumor, disappearance of the liver metastases, and
      reduction in SMV invasion. Therefore, a subtotal stomach-preserving
      pancreatoduodenectomy with partial SMV resection was performed. Following
      surgery, the patient received S-1 chemotherapy again. However, lung metastasis
      appeared. Despite the initiation of gemcitabine(GEM)treatment, the patient
      developed metastases in other parts of the lung and the abdominal wall. She died
      46 months after surgery, but it is noteworthy that the liver metastases were
      manageable. The combination of chemotherapy and surgery was effective in
      prolonging survival in this patient with Stage IV b pancreatic head cancer. 

PMID- 25981663
TI  - [A case of gastric cancer in which grade 2 treatment effects were obtained with
      preoperative two-week S-1 administration].
AB  - In our hospital, a clinical trial on the effects of preoperative 2-week S-1
      administration for advanced gastric cancer is being conducted. A7 5-year-old man
      presented to our hospital with a type 2 tumor(poorly differentiated
      adenocarcinoma)in the pyloric antrum. Subpyloric lymph node enlargement and a c
      T2(MP), N1, M0, Stage II A tumor (according to the gastric cancer handling
      agreement, 14th edition)were diagnosed, and S-1(100mg/day)was subsequently
      administered for 14 days. On day 15, we performed laparoscopy-assisted distal
      gastrectomy, with D2 dissection. Analysis of the resected specimen, ie the
      primary tumor and metastatic lymph nodes, confirmed the effect of the treatment
      as Grade 2, and revealed a type 2 gastric cancer of 30*20mm in size; this tumor
      was downstaged to yp-T1b(SM), N1, Stage I B. No adverse events associated with
      perioperative S-1 were observed, and the postoperative course was good. At the
      latest follow-up(6 years after treatment), no recurrence was observed. 

PMID- 25981664
TI  - [Transvaginal ultrasound-guided core needle biopsy for residual potentially
      malignant ovarian tumors in cases with severe peritoneal adhesion and frozen
      pelvis requiring polysurgery].
AB  - A multiparous woman in her 40s had advanced peritoneal adhesions and frozen
      pelvis from 3 previous surgeries. Endometrial ovarian cysts also remained. After
      the last surgery, imaging showed cysts with a septum and enhanced moieties in the
      Douglas pouch. Highly invasive surgery was anticipated, and the patient underwent
      a transvaginal ultrasound-guided core needle biopsy(TVCNB, 16-gauge needle)with
      full awareness of the risks involved. The histopathological diagnosis was
      adenocarcinoma. We inserted a ureteral stent and performed an S-shaped colon
      resection and standard ovarian cancer surgery after preoperative chemotherapy.
      TVCNB in this case was less invasive and easier to perform than other exploratory
      procedures, and has a low risk of iatrogenic intraperitoneal dissemination even
      if the tumor is malignant. Chemotherapy can be administered before surgery if
      malignancy is detected. In summary, TVCNB is a useful alternative method for
      conducting exploratory operations. 

PMID- 25981665
TI  - Structural Insights into the Dynamic Process of beta2-Adrenergic Receptor
      Signaling.
AB  - G-protein-coupled receptors (GPCRs) transduce signals from the extracellular
      environment to intracellular proteins. To gain structural insight into the
      regulation of receptor cytoplasmic conformations by extracellular ligands during
      signaling, we examine the structural dynamics of the cytoplasmic domain of the
      beta2-adrenergic receptor (beta2AR) using (19)F-fluorine NMR and double electron
      electron resonance spectroscopy. These studies show that unliganded and inverse
      agonist-bound beta2AR exists predominantly in two inactive conformations that
      exchange within hundreds of microseconds. Although agonists shift the equilibrium
      toward a conformation capable of engaging cytoplasmic G proteins, they do so
      incompletely, resulting in increased conformational heterogeneity and the
      coexistence of inactive, intermediate, and active states. Complete transition to
      the active conformation requires subsequent interaction with a G protein or an
      intracellular G protein mimetic. These studies demonstrate a loose allosteric
      coupling of the agonist-binding site and G-protein-coupling interface that may
      generally be responsible for the complex signaling behavior observed for many
      GPCRs. 

PMID- 25981666
TI  - Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.
AB  - Cells adapt to temperature shifts by adjusting levels of lipid desaturation and
      membrane fluidity. This fundamental process occurs in nearly all forms of life,
      but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily
      conserved Caenorhabditis elegans gene acdh-11 (acyl-CoA dehydrogenase [ACDH])
      facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH
      deficiency causes the most common inherited disorders of fatty acid oxidation,
      with syndromes that are exacerbated by hyperthermia. Heat upregulates acdh-11
      expression to decrease fat-7 expression. We solved the high-resolution crystal
      structure of ACDH-11 and established the molecular basis of its selective and
      high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12
      chain fatty acids and prevents these fatty acids from activating nuclear hormone
      receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat
      adaptation by linking temperature shifts to regulation of lipid desaturase levels
      and membrane fluidity via an unprecedented mode of fatty acid signaling. 

PMID- 25981668
TI  - Characterization of complex phase steel using backscattered electron images with
      controlled collection angles.
AB  - For optimizing the microstructure of complex phase (CP) steels, characterization
      using scanning electron microscopy (SEM) is powerful because it allows
      observations from very low to high magnification. SEM specimens of steels are
      often etched in order to distinguish between the different phases by producing
      topographic information. This is however an 'indirect' method of
      characterization, which does not give precise structural information. We have
      developed a new technique for the selective imaging of the martensite (M) phase
      in a ferritic (F)-M complex phase steel. Backscattered electron (BSE) images at
      15-20 kV were recorded by systematically changing the collection angle theta,
      where theta is measured from the specimen surface. When theta was 30-45 degrees ,
      strong channeling contrast was observed. For lower values of theta, it is the low
      energy loss electrons that mainly contribute to the contrast. As theta increases,
      the M phase exhibits brighter contrast. When theta exceeds 60 degrees , a
      selective imaging of the M phase is achieved. This is not because martensite has
      a larger mean atomic number than ferrite, but is due to the fact that martensite
      has a high crystallographic defect density. Anomalously bright M contrast is due
      to multiple scattering of BSE due to the high density of planar defects and
      dislocations. Low angle BSE allows high resolution characterization of complex
      microstructures, while high angle BSE gives quantitative assessment of the
      distribution and the volume fraction of the martensite phase. 

PMID- 25981667
TI  - The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated
      Phosphorylation.
AB  - The circadian timing system synchronizes cellular function by coordinating
      rhythmic transcription via a transcription-translational feedback loop. How the
      circadian system regulates gene expression at the translational level remains a
      mystery. Here, we show that the key circadian transcription factor BMAL1
      associates with the translational machinery in the cytosol and promotes protein
      synthesis. The mTOR-effector kinase, ribosomal S6 protein kinase 1 (S6K1), an
      important regulator of translation, rhythmically phosphorylates BMAL1 at an
      evolutionarily conserved site. S6K1-mediated phosphorylation is critical for
      BMAL1 to both associate with the translational machinery and stimulate protein
      synthesis. Protein synthesis rates demonstrate circadian oscillations dependent
      on BMAL1. Thus, in addition to its critical role in circadian transcription,
      BMAL1 is a translation factor that links circadian timing and the mTOR signaling
      pathway. More broadly, these results expand the role of the circadian clock to
      the regulation of protein synthesis. 

PMID- 25981670
TI  - Fe3O4 nanoflakes in an N-doped carbon matrix as high-performance anodes for
      lithium ion batteries.
AB  - Fe3O4 nanoflakes in an N-doped carbon matrix (Fe3O4 NF@NC) were prepared by
      solvothermal synthesis of Fe3O4 nanoflakes and in situ polymerization of pyrrole
      on the surface of Fe3O4 followed by heat treatment. The Fe3O4 NF@NC is composed
      of Fe3O4 nanoflakes with a width of 50-60 nm and a thickness of 10 nm dispersed
      in the N-doped carbon matrix. The carbon content varies from 18% to 50% on
      controlling the amount of pyrrole added, therefore the Fe3O4 NF@NC with 44%
      carbon content performs the best. Due to the cooperation of the two-dimensional
      (2D) structure of Fe3O4 nanoflakes and the N-doped carbon matrix, the obtained
      Fe3O4 NF@NC (44% carbon content) exhibits electrochemical performance with a
      reversible capacity of 1046 mA h g(-1) at 0.2 C (1 C = 924 mA g(-1)) over 200
      cycles, 662 mA h g(-1) at 1 C after 500 cycles and 600 mA h g(-1) at 5 C over 200
      cycles. 

PMID- 25981669
TI  - Development of Timd2 as a reporter gene for MRI.
AB  - PURPOSE: To assess the potential of an MRI gene reporter based on the ferritin
      receptor Timd2 (T-cell immunoglobulin and mucin domain containing protein 2),
      using T1- and T2-weighted imaging. METHODS: Pellets of cells that had been
      modified to express the Timd2 transgene, and incubated with either iron-loaded or
      manganese-loaded ferritin, were imaged using T1- and T2-weighted MRI. Mice were
      also implanted subcutaneously with Timd2-expressing cells and the resulting
      xenograft tissue imaged following intravenous injection of ferritin using T2
      weighted imaging. RESULTS: Timd2-expressing cells, but not control cells, showed
      a large increase in both R2 and R1 in vitro following incubation with iron-loaded
      and manganese-loaded ferritin, respectively. Expression of Timd2 had no effect on
      cell viability or proliferation; however, manganese-loaded ferritin, but not iron
      loaded ferritin, was toxic to Timd2-expressing cells. Timd2-expressing xenografts
      in vivo showed much smaller changes in R2 following injection of iron-loaded
      ferritin than the same cells incubated in vitro with iron-loaded ferritin.
      CONCLUSION: Timd2 has demonstrated potential as an MRI reporter gene, producing
      large increases in R2 and R1 with ferritin and manganese-loaded ferritin
      respectively in vitro, although more modest changes in R2 in vivo. Manganese
      loaded apoferritin was not used in vivo due to the toxicity observed in vitro.
      Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance.

PMID- 25981671
TI  - Third-party disability in carers of people with dysphagia following non-surgical
      management for head and neck cancer.
AB  - PURPOSE: Third-party disability pertains to the consequences of a person's
      impairment which impacts on the functioning and ability of their family members
      or significant others. With the emergence of research demonstrating the pervasive
      effects of dysphagia following head and neck cancer (HNC) on the carer, the aim
      of this study was to identify the International Classification of Functioning,
      Disability and Health (ICF) domains and categories that describe the third-party
      disability of carers of people with dysphagia following HNC. METHOD: Twelve
      carers of people with dysphagia following HNC participated in individual semi
      structured, in-depth interviews. Categories and sub-categories identified from
      the qualitative analysis were mapped to the ICF using the established linking
      rules. RESULTS: The majority of the categories and sub-categories from the
      qualitative analysis were successfully linked to the ICF with most linking to the
      Activities and Participation component. A number of contextual factors were also
      identified as impacting on the functioning of carers. CONCLUSIONS: The ICF can be
      successfully used to describe the third-party disability in carers of people with
      dysphagia following HNC management. This information could be used by clinicians,
      researchers and policy makers to help establish evidence-based guidelines that
      include carers in the assessment and management of dysphagia associated with HNC.
      IMPLICATIONS FOR REHABILITATION: Clinical levels of distress and reduced quality
      of life have been associated with caring for a person with dysphagia following
      head and neck cancer. The flow-on effects of dysphagia experienced by a carer or
      close family member can be understood as a third-party disability, which impacts
      on their functioning, activities and participation in the context of the
      environment and personal factors. Using the ICF to describe the indirect effects
      of dysphagia on the carer may help to guide the assessment and support of this
      population, and advocate for the inclusion of the concerns of the carer in
      dysphagia management.

PMID- 25981672
TI  - Synergistically Improved Anti-tumor Efficacy by Co-delivery Doxorubicin and
      Curcumin Polymeric Micelles.
AB  - P-gp mediated drug efflux has been recognized as a major obstacle limiting the
      success of cancer chemotherapy. To overcome this issue, doxorubicin (DOX) and
      curcumin (Cur; P-gp inhibitor and apoptosis inhibitor) co-encapsulated pegylated
      polymeric micelles ((DOX+Cur)-PMs) were designed, prepared and characterized to
      simultaneously deliver chemotherapeutic drug and multidrug resistance (MDR)
      modulator to tumor sites. The (DOX+Cur)-PMs were spherical nano-size particle,
      with a loading content of 6.83%, and high colloidal stability. Co-delivery
      micelles exhibited excellent cytotoxicity by reversing MDR, promoting cellular
      uptake and enhancing cellular apoptosis in MCF7/Adr cells. The tumor growth
      inhibitory effect of (DOX+Cur)-PMs in 4T1-bearing mice was more effective
      compared with the combination solution of DOX and Cur and even DOX-PMs. In
      conclusion, simultaneous delivery of DOX and Cur by (DOX+Cur)-PMs has been
      demonstrated to be a promising approach for overcoming MDR and improving
      antitumor efficacy. 

PMID- 25981673
TI  - Identification of Sex-Specific Markers Reveals Male Heterogametic Sex
      Determination in Pseudobagrus ussuriensis.
AB  - Comprehending sex determination mechanism is a first step for developing sex
      control breeding biotechnologies in fish. Pseudobagrus ussuriensis, one of bagrid
      catfishes in Bagridae, had been observed to have about threefold size dimorphism
      between males and females, but its sex determination mechanism had been unknown.
      In this study, we firstly used the amplified fragment length polymorphism (AFLP)
      based screening approach to isolate a male-specific DNA fragment and thereby
      identified a 10,569 bp of male-specific sequence and a 10,365 bp of female
      related sequence by genome walking in the bagrid catfish, in which a substantial
      genetic differentiation with 96.35 % nucleotide identity was revealed between
      them. Subsequently, a high differentiating region of 650 bp with only 70.26 %
      nucleotide identity was found from the corresponding two sequences, and three
      primer pairs of male-specific marker, male and female-shared marker with
      different length products in male and female genomes, and female-related marker
      were designed. Significantly, when these markers were used to identify genetic
      sex of the bagrid catfish, only male individuals was detected to amplify the male
      specific marker fragment, and female-related marker was discovered to produce
      dosage association in females and in males. Our current data provide significant
      genetic evidence that P. ussuriensis has heterogametic XY sex chromosomes in
      males and homogametic XX sex chromosomes in females. Therefore, sex determination
      mechanism of P. ussuriensis is male heterogametic XX/XY system.

PMID- 25981675
TI  - The effect of mare's age on multiple ovulation rate, embryo recovery, post
      transfer pregnancy rate, and interovulatory interval in a commercial embryo
      transfer program in Argentina.
AB  - Advanced maternal age is an important predisposing factor on the reduction of
      reproductive efficiency. The aim of this study was to evaluate the effect of
      donor's age on several reproductive parameters in a commercial equine embryo
      transfer program. Donors were classified into 3 age groups: Group 1=fillies (3
      and 4 years old), Group 2=middle age mares (aged 5-10) and Group 3=old mares
      (aged 13-25). Embryo recovery, multiple ovulation and pregnancy rates and
      interovulatory intervals were compared amongst age groups. Group 1 (171/244,
      70.1%) and Group 2 (774/1081, 71.6%) had a higher (P<0.005) embryo recovery rate
      than Group 3 (385/701, 54.9%). Groups 2 and 3 were 2.5 and 3.4 times more likely
      to have multiple ovulations than Group 1 (P<0.05), respectively. The effect of
      age group on pregnancy rate was not significant (P>0.05). The interovulatory
      intervals length was influenced by individual mare (P<0.001), age (P<0.04), Day
      of flushing (P=0.009) and by month (P<0.012). The overall mean interovulatory
      interval of Group 1 (16.4+/-0.17 days) and Group 2 (16.6+/-0.12 days) was not
      different (P>0.05), but was shorter than the one of Group 3 (17.4+/-0.15 days;
      P<0.04). The embryo recovery rate of flushings from Groups 1 and 2 was influenced
      by the length of the previous interovulatory interval (P=0.03). 

PMID- 25981674
TI  - Direct inhibition of retinoic acid catabolism by fluoxetine.
AB  - Recent evidence from animal and human studies suggests neuroprotective effects of
      the SSRI fluoxetine, e.g., in the aftermath of stroke. The underlying molecular
      mechanisms remain to be fully defined. Because of its effects on the cytochrome
      P450 system (CYP450), we hypothesized that neuroprotection by fluoxetine is
      related to altered metabolism of retinoic acid (RA), whose CYP450-mediated
      degradation in brain tissue constitutes an important step in the regulation of
      its site-specific auto- and paracrine actions. Using traditional pharmacological
      in vitro assays, the effects of fluoxetine on RA degradation were probed in crude
      synaptosomes from rat brain and human-derived SH-SY5Y cells, and in cultures of
      neuron-like SH-SY5Y cells. Furthermore, retinoid-dependent effects of fluoxetine
      on neuronal survival following glutamate exposure were investigated in rat
      primary neurons cells using specific retinoid receptor antagonists. Experiments
      revealed dose-dependent inhibition of synaptosomal RA degradation by fluoxetine
      along with dose-dependent increases in RA levels in cell cultures. Furthermore,
      fluoxetine's neuroprotective effects against glutamate excitotoxicity in rat
      primary neurons were demonstrated to partially depend on RA signaling. Taken
      together, these findings demonstrate for the first time that the potent,
      pleiotropic antidepressant fluoxetine directly interacts with RA homeostasis in
      brain tissue, thereby exerting its neuroprotective effects. 

PMID- 25981676
TI  - Effects of non-lactating period length on the subsequent calving ease and
      reproductive performance of Holstein, Brown Swiss and the crosses.
AB  - The aim of this study was to evaluate the effects of the non-lactating period
      (NLP) length on the subsequent calving ease and reproductive performance of the
      purebred Holstein (HO), Brown Swiss (BS) and F1 crosses (BF) of these breeds. The
      NLP length was classified into four categories: D1: <45d; D2: 45-60d; D3: 60-75d;
      and D4: >75d. The lesser incidence of calving difficulty in the purebred HO and
      BF crossbred cows was recorded at D3, with no significant differences with D2
      [11.6% and 9.5%; Crude Odds Ratio (COR)=1.10 and 0.84, respectively]. However,
      the minimum incidence of calving difficulty in the purebred BS cows was at the
      same NLP length with significant differences with D2 (3.8%; COR=0.31). All
      reproductive indices of the purebred HO cows were less as the NLP length
      increased. However, lesser estimates of calving interval and days non-pregnant in
      purebred BS and BF crossbred cows were recorded at longer (D3) NLP (350 and 328d;
      112 and 133d, respectively). Purebred HO cows had decreased milk production at
      extremely short (D1) and long (D4) NLP. Purebred BS cows, however, were more
      persistent in milk production and had more consistent body condition scores
      (BCS). In conclusion, shortening the NLP of the purebred HO cows in addition to
      making minimum changes in diet composition could be an appropriate solution for
      improving reproduction. Purebred BS and BF crossbred cows were more persistent in
      milk production and tolerated the diet changes during the NLP. 

PMID- 25981677
TI  - Executive function in children with externalizing and comorbid internalizing
      behavior problems.
AB  - BACKGROUND: The goal of this study is to investigate differences in executive
      function (EF) in children with different levels of disruptive behavior problems
      (DBP). METHODS: Ninety-three children between 7 and 12 years old with DBP were
      compared to 63 normally developing peers on a battery of EF tasks that varied in
      the amount of required emotion regulation ('hot' EF). RESULTS: Differences in EF
      were found between DBP and comparison groups as indexed by hot EF tasks. Self
      reported emotion scales, in conjunction with physiological recordings of heart
      rate, confirmed that emotions were elicited during hot EF. CONCLUSIONS: Results
      suggest that difficulties in hot EF underlie externalizing problem behaviors in
      middle childhood.

PMID- 25981678
TI  - Inhibition of differentiation of monocyte to macrophages in atherosclerosis by
      oligomeric proanthocyanidins -In-vivo and in-vitro study.
AB  - Monocyte to macrophage differentiation is a key event in the progression of
      atherosclerosis. An understanding on the fundamental molecular mechanisms and the
      identification of regulatory mechanisms behind this differentiation may aid in
      the identification of new therapeutic strategies. Inhibition of this phenomenon
      will form first line of defense in the prevention and treatment of
      atherosclerosis. In the current study we explored hypercholesterolemia induced
      monocyte to macrophage differentiation in-vivo (Wistar rats) leading to
      atherosclerosis and OxyLDL, M-CSF induced monocyte differentiation in-vitro (U937
      cells). Oligomeric proanthocyanidin (OPC) isolated from Crataegus oxyacantha was
      tested for its efficacy in downregulating this differentiation and in preventing
      atherogenic disturbances. Cholesterol cholic acid diet induced an increased
      monocyte to macrophage differentiation by upregulating MCP1 and VCAM1 which
      induced the inflammatory cytokines that further substantiated the monocyte
      conversion and infiltration into the vascular walls. On addition of OxyLDL and M
      CSF to U937 cells, macrophage markers CD36 and CD 68, PPARgamma, MMP2 and 9 were
      elevated, suggesting differentiation. OPC downregulated this differentiation and
      thus could prevent the initiation of atherosclerosis. 

PMID- 25981680
TI  - Chromogenic Photonic Crystals Enabled by Novel Vapor-Responsive Shape-Memory
      Polymers.
AB  - A new type of shape-memory polymer (SMP) is developed by integrating scientific
      principles drawn from two disparate fields: the fast-growing photonic crystal and
      SMP technologies. This new SMP enables room-temperature operation for the entire
      shape-memory cycle and instantaneous shape recovery triggered by exposure to a
      variety of organic vapors. 

PMID- 25981679
TI  - miRVine: a microRNA expression atlas of grapevine based on small RNA sequencing.
AB  - BACKGROUND: miRNAs are the most abundant class of small non-coding RNAs, and they
      are involved in post-transcriptional regulations, playing a crucial role in the
      refinement of genetic programming during plant development. Here we present a
      comprehensive picture of miRNA regulation in Vitis vinifera L. plant during its
      complete life cycle. Furthering our knowledge about the post-transcriptional
      regulation of plant development is fundamental to understand the biology of such
      an important crop. RESULTS: We analyzed 70 small RNA libraries, prepared from
      berries, inflorescences, tendrils, buds, carpels, stamens and other samples at
      different developmental stages. One-hundred and ten known and 175 novel miRNAs
      have been identified and a wide grapevine expression atlas has been described.
      The distribution of miRNA abundance reveals that 22 novel miRNAs are specific to
      stamen, and two of them are, interestingly, involved in ethylene biosynthesis,
      while only few miRNAs are highly specific to other organs. Thirty-eight miRNAs
      are present in all our samples, suggesting a role in key regulatory circuit. On
      the basis of miRNAs abundance and distribution across samples and on the
      estimated correlation, we suggest that miRNA expression define organ identity. We
      performed target prediction analysis and focused on miRNA expression analysis in
      berries and inflorescence during their development, providing an initial
      functional description of the identified miRNAs. CONCLUSIONS: Our findings
      represent a very extensive miRNA expression atlas in grapevine, allowing the
      definition of how the spatio-temporal distribution of miRNAs defines organ
      identity. We describe miRNAs abundance in specific tissues not previously
      described in grapevine and contribute to future targeted functional analyses.
      Finally, we present a deep characterization of miRNA involvement in berry and
      inflorescence development, suggesting a role for miRNA-driven hormonal
      regulation.

PMID- 25981681
TI  - Human dignity and the creation of human-nonhuman chimeras.
AB  - In this work I present a detailed critique of the dignity-related arguments that
      have been advanced against the creation of human-nonhuman chimeras that could
      possess human-like mental capacities. My main claim is that the arguments so far
      advanced are incapable of grounding a principled objection against the creation
      of such creatures. I conclude that these arguments have one, or more, of the
      following problems: (a) they confuse the ethical assessment of the creation of
      chimeras with the ethical assessment of how such creatures would be treated in
      specific contexts (e.g. in the laboratory), (b) they misrepresent how a being
      could be treated solely as means towards others' ends, 

PMID- 25981682
TI  - Preparing patients at high risk of falls for discharge home after rehabilitation:
      Do we meet the guidelines?
AB  - AIM: To determine whether rehabilitation inpatients at high risk of falls receive
      adequate falls risk assessment, management and handover on discharge as per
      Australian Best Practice Guidelines. METHODS: Medical records of 121 people who
      received inpatient rehabilitation were retrospectively screened; records of 50
      people discharged home and at high falls risk (fall in last 12 months, fall
      preceding/during admission) were audited. Data extracted included falls risk
      identification during rehabilitation and in discharge documentation; falls risk
      factors assessed; and fall prevention strategies implemented. RESULTS: Discharge
      documentation correctly identified falls risk for just nine of the 50 people.
      Patients at high falls risk had a median of 8.0 (interquartile range 6-10) of 17
      risk factors. There was limited evidence of assessment for osteoporosis (n = 8),
      footwear (n = 4) and visual assessment in the previous 2 years (n = 1). Patients
      received a median of 6.5 (interquartile range 5-9) out of 16 possible strategies.
      Common strategies were mobility (n = 48), strength (n = 44) and Personal Activity
      of Daily Living training (n = 43). For 12 risk factors, if the factor was
      present, there was evidence of a strategy in more than 80% of records.
      CONCLUSIONS: There was little evidence that people at high risk of falls received
      systematic falls risk assessment during rehabilitation. When a risk was
      identified, generally a strategy was implemented. However, failure to assess some
      risk factors might have limited fall prevention strategies offered. Failure to
      adequately address risks during hospitalization could contribute to falls post
      discharge. Geriatr Gerontol Int 2016; 16: 570-576.

PMID- 25981683
TI  - Structured Benefit-risk assessment: a review of key publications and initiatives
      on frameworks and methodologies.
AB  - Introduction The conduct of structured benefit-risk assessment (BRA) of
      pharmaceutical products is a key area of interest for regulatory agencies and the
      pharmaceutical industry. However, the acceptance of a standardized approach and
      implementation are slow. Statisticians play major roles in these organizations,
      and have a great opportunity to be involved and drive the shaping of future BRA.
      Method We performed a literature search of recent reviews and initiatives
      assessing BRA methodologies, and grouped them to assist those new to BRA in
      learning, understanding, and choosing methodologies. We summarized the key points
      and discussed the impact of this emerging field on various stakeholders,
      particularly statisticians in the pharmaceutical industry. Results We provide
      introductory, essential, special interest, and further information and
      initiatives materials that direct readers to the most relevant materials, which
      were published between 2000 and 2013.  Based on recommendations in these
      materials we supply a toolkit of advocated BRA methodologies. Discussion Despite
      initiatives promoting these methodologies, there are still barriers, one of which
      being the lack of a consensus on the most appropriate methodologies among
      stakeholders. However, this opens up opportunities, for statisticians in the
      pharmaceutical industry especially, to champion appropriate BRA methodology use
      throughout the pharmaceutical product lifecycle. Conclusions This article may
      serve as a starting point for discussions and to reach a mutual consensus for
      methodology selection in a particular situation. Regulators and pharmaceutical
      industry should continue to collaborate to develop and take forward BRA
      methodologies, and by clear communication develop a mutual understanding of the
      key issues. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25981684
TI  - A Minority Stress Model for Suicidal Ideation in Gay Men.
AB  - There is a dearth of research on mechanisms underlying higher rates of suicidal
      ideation among gay men compared to heterosexual men. The purpose of this study
      was to establish the link between social/psychological predictor variables and
      suicidal ideation by testing a hypothesized minority stress model. Structural
      equation modeling was used to assess the relationships posited in the model using
      data from a community sample of 167 gay men. Model fit was adequate and
      hypothesized relationships were partially supported. Also, depressive symptoms
      partially mediated the relationship between (less) outness predicting suicidal
      ideation. These findings imply that therapeutic approaches targeting the coming
      out process may be more effective than approaches targeting internalized
      homophobia when suicidal ideation is indicated in the clinical presentation of
      gay and bisexual men. 

PMID- 25981685
TI  - Identification of MK-8133: An orexin-2 selective receptor antagonist with
      favorable development properties.
AB  - Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm
      for the treatment of insomnia and related disorders. Herein, molecules related to
      the dual orexin receptor antagonist filorexant were transformed into compounds
      that were selective for the OX2R subtype. Judicious selection of the substituents
      on the pyridine ring and benzamide groups led to 6b; which was highly potent,
      OX2R selective, and exhibited excellent development properties. 

PMID- 25981686
TI  - ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor
      (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon
      activity.
AB  - ortho-Carboranylphenoxy derivatives were synthesized and evaluated for their
      ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell
      based reporter gene assay. Among the compounds synthesized, compound 1d showed
      the most significant inhibition of hypoxia-induced HIF-1 transcriptional activity
      with the IC50 of 0.53MUM. Furthermore, compound 1h was found to possess the most
      significant inhibition of heat shock protein (HSP) 60 chaperon activity among the
      reported inhibitors: the IC50 toward the porcine heart malate dehydrogenase (MDH)
      refolding assay was 0.35MUM. 

PMID- 25981687
TI  - Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors.
AB  - Drug resistant infections are becoming common worldwide and new strategies for
      drug development are necessary. Here, we report the synthesis and evaluation of
      2,4-dinitrophenylsulfonamides, which are donors of sulfur dioxide (SO2), a
      reactive sulfur species, as methicillin-resistant Staphylococcus aureus (MRSA)
      inhibitors. N-(3-Methoxyphenyl)-2,4-dinitro-N-(prop-2-yn-1-yl)benzenesulfonamide
      (5e) was found to have excellent in vitro MRSA inhibitory potency. This compound
      is cell permeable and treatment of MRSA cells with 5e depleted intracellular
      thiols and enhanced oxidative species both results consistent with a mechanism
      involving thiol activation to produce SO2. 

PMID- 25981689
TI  - Synthesis and bioactivity of tripolinolate A from Tripolium vulgare and its
      analogs.
AB  - A new coniferol derivative, named as tripolinolate A (1), and 11 known compounds
      (2-12) were isolated from whole plants of Tripolium vulgare Nees. The structure
      of this new compound was determined as 4-(2S-methylbutyryl)-9-acetyl-coniferol
      based on its NMR and HRESIMS spectral analyses. A simple and efficient method was
      designed to prepare tripolinolate A and its 19 analogs including nine new
      chemical entities for bioactive assay. Tripolinolate A and its analog 4,9
      diacetyl-coniferol were found to be the two most active compounds that
      significantly inhibited the proliferation of different cancer cell lines with
      IC50 values ranging from 0.36 to 12.9MUM and induced apoptosis in tumor cells.
      Structure-activity relationship analysis suggested that the molecular size of
      acyl moieties at C-4 and C-9 position might have an effect on the activity of
      this type of coniferol derivatives. 

PMID- 25981688
TI  - A new antibacterial octaketide and cytotoxic phenylethanoid glycosides from
      Pogostemon cablin (Blanco) Benth.
AB  - A new octaketide, named cytosporone V (1), and two other known phenylethanoid
      glycosides (2-3), were isolated from the aerial parts of Pogostemon cablin
      (Blanco) Benth. The structure of 1 was elucidated by a combination of extensive
      spectroscopic analyses, including extensive 2D NMR and HR-MS. Compounds 1-3
      displayed weak antibacterial activity against two gram-positive bacteria,
      Bacillus subtilis and Staphylococcus aureus. All isolates were also evaluated for
      their antiproliferative activities against four human tumor cell lines (A549, SK
      OV-3, SK-MEL-2, and HCT-15). Compounds 2 and 3 showed significant cytotoxicity
      against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC50 values ranging
      from 2.73 to 9.52 MUM.

PMID- 25981690
TI  - 2-Aminoalkyl nicotinamide derivatives as pure inverse agonists of the ghrelin
      receptor.
AB  - New inverse agonists of the ghrelin receptor (ghrelinR) were obtained through
      high-throughput screening and subsequent structural modification of 2-aminoalkyl
      nicotinamide derivatives. The key structural feature to improve in vitro activity
      was the introduction of a diazabicyclo ring at the 5-position of the pyridine
      ring. The final product showed potent inverse agonist activity and, despite its
      low brain permeability, reduced food intake in both normal and obese mice. These
      results implied that peripheral ghrelinR activity is important for appetite
      control and that a peripheral ghrelinR inverse agonist could be an anti-obesity
      drug with reduced risk of central nervous system (CNS)-related side effects. 

PMID- 25981691
TI  - Posture Influence on the Pendulum Test of Spasticity in Patients with Spinal Cord
      Injury.
AB  - The study aims to investigate the influence of different postures on spasticity
      results by pendulum test in patients with spinal cord injury (SCI). The setting
      was at the University of Campinas (UNICAMP), Campinas, SP, Brazil. Five
      individuals with SCI and five individuals in the control group were included. All
      individuals went through the pendulum test in three different positions: supine,
      semi-supine at an angle of 30 degrees , and sitting up at an angle of 60 degrees
      . An electrogoniometer was attached to the right leg for measurement of knee
      joint angles. All situations were performed five times. Blood pressure was
      monitored during tests. Relaxation index (RI), normalized relaxation index (RIn),
      test duration in seconds, initial flexion angle, and resting angle were analyzed
      at three different positions. Results were compared between different positions,
      and statistically no differences were found. In individuals with SCI, RI (1.83 +/
      0.2), RIn (1.14 +/- 0.13), and test duration values (13.95 +/- 4.14), in sitting
      up position, were similar to the control group results. In sitting up position,
      patients showed spasticity reduction. However, the other two postures produce
      pain and increase blood pressure in patients with tetraplegia. Therefore, these
      postures should be avoided in patients with lesions above T6, due to possible
      autonomic dysreflexia symptoms. 

PMID- 25981692
TI  - The '16-hour rule': a giant step, but in which direction?

PMID- 25981693
TI  - The genomics of micronutrient requirements.
AB  - Healthy nutrition is accepted as a cornerstone of public health strategies for
      reducing the risk of noncommunicable conditions such as obesity, cardiovascular
      disease, and related morbidities. However, many research studies continue to
      focus on single or at most a few factors that may elicit a metabolic effect.
      These reductionist approaches resulted in: (1) exaggerated claims for nutrition
      as a cure or prevention of disease; (2) the wide use of empirically based dietary
      regimens, as if one fits all; and (3) frequent disappointment of consumers,
      patients, and healthcare providers about the real impact nutrition can make on
      medicine and health. Multiple factors including environment, host and microbiome
      genetics, social context, the chemical form of the nutrient, its
      (bio)availability, and chemical and metabolic interactions among nutrients all
      interact to result in nutrient requirement and in health outcomes. Advances in
      laboratory methodologies, especially in analytical and separation techniques, are
      making the chemical dissection of foods and their availability in physiological
      tissues possible in an unprecedented manner. These omics technologies have opened
      opportunities for extending knowledge of micronutrients and of their metabolic
      and endocrine roles. While these technologies are crucial, more holistic
      approaches to the analysis of physiology and environment, novel experimental
      designs, and more sophisticated computational methods are needed to advance our
      understanding of how nutrition influences health of individuals. 

PMID- 25981694
TI  - beta-Carotene-induced apoptosis is mediated with loss of Ku proteins in gastric
      cancer AGS cells.
AB  - High dietary intakes and high blood levels of beta-carotene are associated with a
      decreased incidence of various cancers. The anticancer effect of beta-carotene is
      related to its pro-oxidant activity. DNA repair Ku proteins, as a heterodimer of
      Ku70 and Ku80, play a crucial role in DNA double-strand break repair. Reductions
      in Ku70/80 contribute to apoptosis. Previously, we showed that reactive oxygen
      species (ROS) activate caspase-3 which induces degradation of Ku proteins. In the
      present study, we investigated the mechanism of beta-carotene-induced apoptosis
      of gastric cancer AGS cells by determining cell viability, DNA fragmentation,
      apoptotic indices (increases in cytochrome c and Bax, decrease in Bcl-2), ROS
      levels, mitochondrial membrane potential, caspase-3 activity, Ku70/80 levels, and
      Ku-DNA-binding activity of the cells treated with or without antioxidant N-acetyl
      cysteine and caspase-3 inhibitor z-DEVED-fmk. As a result, beta-carotene induced
      apoptosis (decrease in cell viability, increases in DNA fragmentation and
      apoptotic indices) and caspase-3 activation, but decreased Ku70/80 levels and Ku
      DNA-binding activity. beta-Carotene-induced alterations (increase in caspase-3
      activity, decrease in Ku proteins) and apoptosis were inhibited by N-acetyl
      cysteine and z-DEVED-fmk. Increment of intracellular and mitochondrial ROS levels
      and loss of mitochondrial membrane potential were suppressed by N-acetyl
      cysteine, but not by z-DEVED-fmk in beta-carotene-treated cells. Therefore, beta
      carotene-induced increases in ROS and caspase-3 activity may lead to reduction of
      Ku70/80 levels, which results in apoptosis in gastric cancer cells. Loss of Ku
      proteins might be the underlying mechanism for beta-carotene-induced apoptosis in
      gastric cancer cells. 

PMID- 25981695
TI  - Iron deficiency upregulates Egr1 expression.
AB  - Iron-deficient anemia is a prevalent disease among humans. We searched for genes
      regulated by iron deficiency and its regulated mechanism. cDNA microarrays were
      performed using Hepa1c1c7 cells treated with 100 MUM desferrioxamine (DFO), an
      iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20
      fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR.
      This activation was not seen by ferric ammonium citrate (FAC). DFO increased the
      transcriptional activity of Egr1-luc (-604 to +160) and serum response element
      (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced
      Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained
      ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059)
      prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk
      1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species
      (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced
      iron deficiency upregulates Egr1 in part through transcriptional activation via
      ERK and Elk-1 signals, which may be important in the regulation of cell death in
      hepatoma cells. Our study demonstrated that iron depletion controlled the
      expression of Egr1, which might contribute to decisions about cellular fate in
      response to iron deficiency. 

PMID- 25981696
TI  - The glycobiology of the CD system: a dictionary for translating marker
      designations into glycan/lectin structure and function.
AB  - The profile of cell surface molecules, the biochemical platform for cellular
      communication, can be likened to a molecular fingerprint. Historically, raising
      monoclonal antibodies by immunization with cells has been instrumental in
      obtaining tools suited for phenotyping and functional analysis. Initially for
      leukocyte antigens, the resulting cluster of differentiation (CD) nomenclature
      has become a popular system for classification. Glycans presented on proteins or
      lipids and receptors for carbohydrate structures (lectins) are part of the CD
      list. Our review presents biochemical and biomedical highlights of the respective
      CD entries. 

PMID- 25981697
TI  - Cu7 S4 Nanosuperlattices with Greatly Enhanced Photothermal Efficiency.
AB  - According to the simulation, the self-assembly of Cu7 S4 nanocrystals would
      enhance the photothermal conversion efficiency (PCE) because of the localized
      surface plasmon resonance effects, which is highly desirable for photothermal
      therapy (PTT). A new strategy to synthesize Cu7 S4 nanosuperlattices with greatly
      enhanced PCE up to 65.7% under irradiation of 808 nm near infrared light is
      reported here. By tuning the surface properties of Cu7 S4 nanocrystals during the
      synthesis via thermolysis of a new single precursor, dispersed nanoparticles
      (NPs), rod-like alignments, and nanosuperlattices are obtained, respectively. To
      explore their PTT applications, these hydrophobic nanostructures are transferred
      into water by coating with home-made amphiphilic polymer while maintaining their
      original structures. Under identical conditions, the PCE are 48.62% and 56.32%
      for dispersed NPs and rod-like alignments, respectively. As expected, when the
      nanoparticles are self-assembled into nanosuperlattices, the PCE is greatly
      enhanced up to 65.7%. This strong PCE, along with their excellent photothermal
      stability and good biocompatibility, renders these nanosuperlattices good
      candidates as PTT agents. In vitro photothermal ablation performances have
      undoubtedly proved the excellent PCE of our Cu7 S4 nanosuperlattices. This
      research offers a versatile and effective solution to get PTT agents with high
      photothermal efficiency. 

PMID- 25981699
TI  - Risk Chart for Future Mortality and Ischaemic Events Following Peripheral Bypass
      Surgery.
AB  - OBJECTIVES: A prediction model to identify determinants and quantify the risk of
      future ischaemic events in patients with peripheral arterial disease (PAD)
      provides a personal risk profile to offer individualized patient care. A risk
      chart was derived and validated in patients who received infrainguinal bypass
      surgery. METHODS: The Bypass Oral anticoagulants or Aspirin Risk Chart (BOA-RC2)
      was based on a pre-defined subgroup of the Dutch BOA trial (N = 482), the
      derivation cohort. The primary outcome event for BOA-RC2 was the composite of all
      cause death, non-fatal myocardial infarction, or non-fatal ischaemic stroke
      during a 10 year follow up. Determinants and long-term risk were identified with
      multivariate Cox regression analyses. Validation of the BOA-RC2 was performed in
      the remaining patients of the complete BOA trial cohort (N = 2,650 - 482 =
      2,168), the validation cohort. RESULTS: The primary outcome event occurred in 67%
      (321/454) of the derivation cohort and in 66% (1,371/2,083) of the validation
      cohort during a median follow up of 6.6 years. The BOA-RC2 included the following
      determinants: age, critical limb ischaemia, diabetes, and a prior vascular
      intervention. The performance of the BOA-RC2 was good with a Brier score of 0.19,
      an area under the curve of 0.73, and a Hosmer-Lemeshow statistic of p = .9.
      CONCLUSIONS: The BOA-RC2 proves to be fit for the prediction of mortality and
      major ischaemic events in patients after peripheral bypass surgery. The BOA-RC2
      can be used to adequately inform the patient about his/her risk of future events
      in an illustrative manner and stress the necessity of preventative measures, such
      as lifestyle adjustments, screening for risk factors, and drug treatments. In the
      future, the BOA-RC2 may be of interest to identify patients at high risk of
      mortality and ischaemic events for clinical research on new therapeutic options.

PMID- 25981701
TI  - Identification and characterization of aldehyde dehydrogenase 9 from Lampetra
      japonica and its protective role against cytotoxicity.
AB  - Aldehyde dehydrogenases (ALDHs), which oxidize aldehyde to corresponding acids,
      play a major role in the detoxification of various endogenous and exogenous
      aldehydes. In this study, we cloned and characterized ALDH9 (designated LjALDH9)
      from Arctic lamprey Lampetra japonica. The open reading frame of LjALDH9 was 1566
      bp, encoding 521 amino acids with a predicted molecular mass of 55.68 kDa.
      LjALDH9 protein had a signal peptide and Aldedh domain with the active site
      Cys315. In addition, LjALDH9 shares high sequence homology with ALDH9 of jawed
      vertebrates. Real-time quantitative PCR revealed that LjALDH9 was highly
      expressed in the buccal gland. A reactive LjALDH9 protein was obtained by
      prokaryotic expression, two-step-denaturing and refolding and affinity
      purification. During enzyme activity analysis of recombinant LjALDH9, we found
      that the most suitable reaction conditions were pH7.0, 16-23  degrees C and
      Mn(2+) as the activator. Our study provides theoretical proof that LjALDH9 plays
      an important role in the parasitic life phase of lamprey.

PMID- 25981700
TI  - Cloning and characterization of aquaglyceroporin genes from rainbow smelt
      (Osmerus mordax) and transcript expression in response to cold temperature.
AB  - Aquaglyceroporins (GLPs) are integral membrane proteins that facilitate passive
      movement of water, glycerol and urea across cellular membranes. In this study,
      GLP-encoding genes were characterized in rainbow smelt (Osmerus mordax mordax),
      an anadromous teleost that accumulates high glycerol and modest urea levels in
      plasma and tissues as an adaptive cryoprotectant mechanism in sub-zero
      temperatures. We report the gene and promoter sequences for two aqp10b paralogs
      (aqp10ba, aqp10bb) that are 82% identical at the predicted amino acid level, and
      aqp9b. Aqp10bb and aqp9b have the 6 exon structure common to vertebrate GLPs.
      Aqp10ba has 8 exons; there are two additional exons at the 5' end, and the
      promoter sequence is different from aqp10bb. Molecular phylogenetic analysis
      suggests that the aqp10b paralogs arose from a gene duplication event specific to
      the smelt lineage. Smelt GLP transcripts are ubiquitously expressed; however,
      aqp10ba transcripts were highest in kidney, aqp10bb transcripts were highest in
      kidney, intestine, pyloric caeca and brain, and aqp9b transcripts were highest in
      spleen, liver, red blood cells and kidney. In cold-temperature challenge
      experiments, plasma glycerol and urea levels were significantly higher in cold-
      compared to warm-acclimated smelt; however, GLP transcript levels were generally
      either significantly lower or remained constant. The exception was significantly
      higher aqp10ba transcript levels in kidney. High aqp10ba transcripts in smelt
      kidney that increase significantly in response to cold temperature in congruence
      with plasma urea suggest that this gene duplicate may have evolved to allow the
      re-absorption of urea to concomitantly conserve nitrogen and prevent freezing.

PMID- 25981702
TI  - Characterization of the arginine kinase isoforms in Caenorhabditis elegans.
AB  - Phosphagen kinases (PKs) are well-studied enzymes involved in energy homeostasis
      in a wide range of animal, protozoan, and even some bacterial species. Recent
      genome efforts have allowed comparative work on the PKs to extend beyond the
      biochemistry of individual proteins to the comparative cellular physiology and
      examining of the role of all PK family members in an organism. The sequencing of
      the Caenorhabditis elegans genome and availability of sophisticated genetic tools
      within that system affords the opportunity to conduct a detailed physiological
      analysis of the PKs from a well known invertebrate for comparison with the
      extensive work conducted on vertebrate systems. As a first step in this effort we
      have carried out a detailed molecular genetic and biochemical characterization of
      the PKs in C. elegans. Our results reveal that C. elegans has five PK genes
      encoding arginine kinases that range in catalytic efficiency (kcat/KM(Arg)) from
      (3.1+/-0.6)*10(4) to (9+/-4)*10(5) M(-1) s(-1). This range is generally within
      the range seen for arginine kinases from a variety of species. Our molecular
      genetic and phylogenetic analysis reveals that the gene family has undergone
      extensive intron loss and gain within the suborder Rhabditina. In addition,
      within C. elegans we find evidence of gene duplication and loss. The analysis
      described here for the C. elegans AKs represents one of the most complete
      biochemical and molecular genetic analysis of a PK family within a genetically
      tractable invertebrate system and opens up the possibility of conducting detailed
      physiological comparisons with vertebrate systems using the sophisticated tools
      available with this model invertebrate system.

PMID- 25981698
TI  - Ruptured Aneurysm Trials: The Importance of Longer-term Outcomes and Meta
      analysis for 1-year Mortality.
AB  - OBJECTIVE: To assess current knowledge for the management of ruptured abdominal
      aortic aneurysm (AAA), based on the 1-year outcomes of 3 recent randomised
      trials. METHODS: An individual patient data meta-analysis of three recent
      randomised trials of endovascular versus open repair, including 817 patients, was
      conducted according to a pre-specified analysis plan, report all-cause mortality
      and re-interventions at 1 year after the index event. RESULTS: Mortality across
      the 3 trials at 1-year was 38.6% for the EVAR or endovascular strategy patient
      groups and 42.8% for the open repair groups, pooled odds ratio 0.84 (95% CI 0.63
      1.11), p = .209. There was no evidence of heterogeneity in the odds ratios
      between trials. When the patients in the endovascular strategy group of the
      IMPROVE trial were restricted to those with proven rupture who were anatomically
      suitable for endovascular repair, the pooled odds ratio reduced slightly to 0.80
      (95% CI 0.56-1.16), p = .240. CONCLUSIONS: After 1 year there is a consistent but
      non-significant trend for lower mortality for EVAR or an endovascular strategy.
      Taken together with the recent gains in health economic outcomes demonstrated at
      1 year in the IMPROVE trial, the evidence suggests that endovascular repair
      should be used more widely for ruptured aneurysms.

PMID- 25981703
TI  - Divergent functions of fibroblast growth factor receptor-like 1 genes in grass
      carp (Ctenopharyngodon idella).
AB  - Fibroblast growth factor receptor-like 1 (FGFRL1) is a novel FGF receptor (FGFR)
      lacking an intracellular tyrosine kinase domain. FGFRs control the proliferation,
      differentiation and migration of cells in various tissues. However the functions
      of FGFRL1 in teleost fish are currently unknown. In this study, we report the
      identification of two fgfrl1 genes in grass carp (Ctenopharyngodon idella) that
      share 56% amino acid sequence identity. Both fgfrl1a and 1b were transcribed
      throughout embryogenesis, and mRNA levels were particularly high during
      somitogenesis. Using in situ hybridization, fgfrl1a transcripts were detected in
      notochord, somites, brain and eye at 14, 24 and 36 h post fertilization (hpf). In
      contrast, fgfrl1b was transcribed mainly in the endoderm at 14 hpf, in the gut
      and proctodeum at 24 hpf, and in the lens, pharyngeal arch and proctodeum at 36
      hpf. In adult fish, fgfrl1a was abundantly expressed in heart, brain and muscle,
      while fgfrl1b was expressed strongly in eye, muscle and gill. Furthermore, both
      genes were significantly (p<0.05) up-regulated in muscle and brain during
      starvation and returned to normal levels rapidly after re-feeding. Exogenous
      treatment with different doses of human growth hormone down-regulated the
      expression of both genes in brain and muscle (p<0.05). These results suggest that
      Fgfrl1a and 1b play divergent roles in regulating growth and development in grass
      carp.

PMID- 25981704
TI  - Dielectric, thermal and mechanical properties of zirconium silicate reinforced
      high density polyethylene composites for antenna applications.
AB  - A low cost and low dielectric loss zirconium silicate (ZrSiO4) reinforced HDPE
      (high-density polyethylene) composite has been developed for antenna
      applications. The 0-3 type composite is prepared by dispersing ZrSiO4 fillers for
      various volume fractions (0.1 to 0.5) in the HDPE matrix by the melt mixing
      process. The composite shows good microwave dielectric properties with a relative
      permittivity of 5.6 and a dielectric loss of 0.003 at 5 GHz at the maximum filler
      loading of 0.5 volume fraction. The composite exhibits low water absorption,
      excellent thermal and mechanical properties. It shows a water absorption of 0.03
      wt%, a coefficient of thermal expansion of 70 ppm per  degrees C and a room
      temperature thermal conductivity of 2.4 W mK(-1). The composite shows a tensile
      strength of 22 MPa and a microhardness of 13.9 kg mm(-2) for the filler loading
      of 0.5 volume fraction. The HDPE-ZrSiO4 composites show good dielectric, thermal
      and mechanical properties suitable for microwave soft substrate applications. A
      microstrip patch antenna is designed and fabricated using the HDPE-0.5 volume
      fraction ZrSiO4 substrate and the antenna parameters are investigated. 

PMID- 25981705
TI  - Obstetrician-Gynecologists' Practices, Statistical Literacy, and Risk
      Communication with Regard to Sexually Transmitted Infections.
AB  - In order to best care for women, obstetrician-gynecologists (ob-gyns) must be
      able to diagnose and treat sexually transmitted infections (STIs), as well as
      effectively communicate risks regarding STIs. This article provides a narrative
      review of studies primarily conducted by the Research Department at the American
      College of Obstetricians and Gynecologists, about missed opportunities for STI
      risk communication. Missed opportunities include the omission or partial
      completion of STI risk assessment and counseling, failure to offer screening or
      testing, lack of follow-up on STI testing/vaccination refusals, and a failure to
      comply with existing guidelines. We also discuss knowledge level, time
      constraints, and gaps in statistical literacy as barriers to STI communication.
      The aim of this article is to highlight common barriers to risk communication,
      discuss their potential impact, and suggest means by which these obstacles can be
      addressed. Future directions for training, education, and research are discussed.

PMID- 25981706
TI  - Sexual Behaviors, Healthcare Interactions, and HIV-Related Perceptions Among
      Adults Age 60 Years and Older: An Investigation by Race/Ethnicity.
AB  - BACKGROUND: Older adults are remaining sexually active for longer periods of
      time, underscoring the need to assess sexual activity patterns in this group and
      identify differences by race/ethnicity, some of which may have implications for
      the development and implementation of sexual risk reduction interventions.
      METHODS: Using data from the 2010 National Social Life, Health, and Aging
      Project, this study examined responses from 1,429 adults aged 60 years and older.
      Multinomial logistic regression compared sexual behaviors, health-related
      indicators, interactions with healthcare professionals, and HIV-related
      perceptions across participants' race/ethnicity. RESULTS: Approximately 81% of
      participants self-reported as non-Hispanic white, 10.59% as African American, and
      8.05% as Hispanic. On average, participants were 69.9 years of age. In the
      previous year, 49.3% of participants engaged in sexual intercourse; only 3% used
      condoms. The majority of participants (83.1%) visited a physician at least twice
      in the previous year, 30.9% had discussed sex with a physician since turning 50,
      and 14.2% had been tested for HIV. Relative to non-Hispanic whites, African
      Americans were more likely to be divorced (OR=3.23, P<0.001) or widowed (OR=2.90,
      P<0.001); have more lifetime sexually transmitted infection (STI) diagnoses
      (OR=1.67, P=0.030); and have paid for sex (OR=2.83, P=0.002). Although African
      Americans had greater perceived risk for HIV infection (OR=1.66, P=0.046), they
      were less likely to have discussed sex with a physician since turning 50
      (OR=0.45, P=0.009). CONCLUSION: Contextualized interventions to improve patient
      provider communication and proactive screening behaviors in sexually-active and
      aging African Americans are needed.

PMID- 25981707
TI  - Current tuberculin reactivity of schoolchildren in the Central African Republic.
AB  - BACKGROUND: The tuberculin skin test (TST) is the recommended method for
      screening for Mycobacterium tuberculosis infection in many countries. We used
      this technique to assess bacillus Calmette-Guerin (BCG) status and to estimate
      the current prevalence and annual rate of latent tuberculosis infection in
      schoolchildren in the Central African Republic. METHODS: Two tuberculin units of
      0.1 ml purified protein derivative TR23 were injected intradermally into the left
      forearm of 2710 children attending school in Bangui and Ombella M'Poko. The
      induration size was interpreted at cut-off points of >= 5 mm, >= 10 mm and >= 15
      mm. The annual infection rate was estimated as the average number of infections
      in the study sample each year between birth and the time of the survey. RESULTS:
      Overall, there was no reaction to the TST (no induration) in 71.7 % (95 CI, 68.3
      75.3 %) of BCG-vaccinated children and 82.9 % (95 CI, 74.1-91.4 %) of non
      vaccinated children. The proportions of children who gave a TST reaction above >=
      10 mm and >= 15 mm cut-off was 18.4 % (95 % CI, 16.8-20.1 %) and 8.9 % (95 % CI,
      7.8-10.0 %), respectively. The proportions of TST reaction above these cut-offs
      were 19.6 % (95 % CI, 17.4-21.9 %) and 8.1 % (95 % CI, 6.7-9.6 %), respectively.
      The annual infection rate was 0.8 % at the cut-off point of >= 15 mm. CONCLUSION:
      This study provides updated data on rates of tuberculosis infection in the
      Central African Republic. It is remarkable that most of the children had negative
      tuberculin reactivity. More studies are required to understand the factors that
      determine the low tuberculin reactivity in this population.

PMID- 25981708
TI  - Income related inequalities in avoidable mortality in Norway: A population-based
      study using data from 1994-2011.
AB  - OBJECTIVE: The aim of this study was to measure income-related inequalities in
      avoidable, amenable and preventable mortality in Norway over the period 1994
      2011. METHODS: We undertook a register-based population study of Norwegian
      residents aged 18-65 years between 1994 and 2011, using data from the Norwegian
      Income Register and the Cause of Death Registry. Concentration indices were used
      to measure income-related inequalities in avoidable, amenable and preventable
      mortality for each year. We compared the trend in income-related inequality in
      avoidable mortality with the trend in income inequality, measured by the Gini
      coefficient for income. RESULTS: Avoidable, amenable and preventable deaths in
      Norway have declined over time. There were persistent pro-poor socioeconomic
      inequalities in avoidable, amenable and preventable mortality, and the degree of
      inequality was larger in preventable mortality than in amenable mortality
      throughout the period. The income-avoidable mortality association was positively
      correlated with income inequalities in avoidable mortality over time. There was
      little or no relationship between variations in the Gini coefficient due to tax
      reforms and socioeconomic inequalities in avoidable mortality. CONCLUSIONS:
      Income-related inequalities in avoidable, amenable and preventable mortality have
      remained relatively constant between 1994 and 2011 in Norway. They were mainly
      correlated with the relationship between income and avoidable mortality rather
      than with variations in the Gini coefficient of income inequality.

PMID- 25981709
TI  - Peripheral conduit and resistance artery function are improved following a
      single, 1-h bout of peristaltic pulse external pneumatic compression.
AB  - INTRODUCTION: External pneumatic compression (EPC) is being employed for a
      widening range of clinical and non-clinical populations. However, EPC devices
      vary markedly in treatment pressures, duty cycles and application sites, and the
      acute effects of whole limb, lower pressure EPC on peripheral vascular function
      have not been determined. PURPOSE: The purpose of this study was to determine the
      acute effects of a single bout of peristaltic pulse EPC on peripheral conduit and
      resistance artery function. METHODS: Twenty (n = 20; males = 12 and females = 8)
      young and apparently healthy subjects (aged 26.1 +/- 8.2 years) participated in
      this study. A sequential EPC device with five inflation zones arranged linearly
      and inflating distal to proximal along the lower limbs was employed with target
      inflation pressures of 70 mmHg for 1 h. Flow-mediated dilation (FMD) of the
      brachial and popliteal arteries was evaluated with ultrasound before and after
      EPC. Venous occlusion plethysmography was employed to evaluate limb blood flow at
      rest and during reactive hyperemia (RH) in the forearm (FBF) and calf (CBF)
      before and after EPC. RESULTS: Peak RH CBF was increased by 9 % after EPC (P <
      0.05), whereas peak RH FBF (-10 %) did not change significantly (P > 0.25).
      Normalized popliteal artery FMD post-EPC (2.24 +/- 1.41) was significantly higher
      than pre-EPC (1.36 +/- 0.67, P = 0.015) and post-sham (1.58 +/- 0.86, P = 0.032)
      values. Similarly, normalized brachial artery FMD post-EPC (1.47 +/- 0.32) was
      significantly higher than pre-EPC (1.11 +/- 0.41, P = 0.004) and post-sham (0.99
      +/- 0.27, P = 0.026) values. CONCLUSION: Acutely, whole limb, lower pressure EPC
      improves conduit artery endothelial function systemically, but only improves RH
      blood flow locally (i.e., compressed limbs).

PMID- 25981710
TI  - Twenty-five years of ambulatory laparoscopic cholecystectomy.
AB  - It is accepted by the surgical community that laparoscopic cholecystectomy (LC)
      is the technique of choice in the treatment of symptomatic cholelithiasis.
      However, more controversial is the standardization of system implementation in
      Ambulatory Surgery because of its different different connotations. This article
      aims to update the factors that influence the performance of LC in day surgery,
      analyzing the 25 years since its implementation, focusing on the quality and
      acceptance by the patient. Individualization is essential: patient selection
      criteria and the implementation by experienced teams in LC, are factors that
      ensure high guarantee of success. 

PMID- 25981711
TI  - Can Normal Fracture Healing Be Achieved When the Implant Is Retained on the Basis
      of Infection? An Experimental Animal Model.
AB  - BACKGROUND: Infection after open fractures is a common complication. Treatment
      options for infections developed after intramedullary nailing surgery remain a
      topic of controversy. We therefore used a rat fracture model to evaluate the
      effects of infection on osseous union when the implant was maintained.
      QUESTIONS/PURPOSES: In a rat model, (1) does infection alter callus strength; (2)
      does infection alter the radiographic appearance of callus; and (3) does
      infection alter the histological properties of callus? METHODS: An open femoral
      fracture was created and fixed with an intramedullary Kirschner wire in 72 adult
      male Sprague-Dawley rats, which were divided into two study groups. In the
      infection group, the fracture site was contaminated with Staphylococcus aureus
      (36 animals), whereas in the control group, there was no bacterial contamination
      (36 animals). No antibiotics were used either for prophylaxis or for treatment.
      We performed biomechanical (maximum torque causing failure and stiffness),
      radiographic (Lane and Sandhu scoring for callus formation), and histologic
      (scoring for callus maturity) assessments at 3 and 6 weeks. The number of
      bacteria colonies on the femur, wire, and soft tissue inside knee were compared
      to validate that we successfully created an infection model. The number of
      bacteria colonies in the soft tissue inside the knee was higher in the infection
      group after 6 weeks than after the third week, demonstrating the presence of
      locally aggressive infection. RESULTS: Infection decreased callus strength at 6
      weeks. Torque to failure (299.07 +/- 65.53 Nmm versus 107.20 +/- 88.81, mean
      difference with 95% confidence interval, 192 [43-340]; p = 0.007) and stiffness
      at 6 weeks (11.28 +/- 2.67 Nmm versus 2.03 +/- 1.68, mean difference with 95%
      confidence interval, 9 [3-16]; p = 0.004) both were greater in the control group
      than in the group with infection. Radiographic analysis at 6 weeks demonstrated
      the fracture line was less distinct (Lane and Sandhu score of 2-3) in the
      infection group and complete union was observed (Lane and Sandhu score of 3-4) in
      the control group (p = 0.001). Semiquantitative histology scores were not
      different between the noninfected controls and the rats with infection (score 10
      versus 9). CONCLUSIONS: Retaining an implant in the presence of an underlying
      infection without antibiotic treatment leads to weaker callus and impedes callus
      maturation compared with noninfected controls in a rat model. Future studies
      might evaluate whether antibiotic treatment would modify this result. CLINICAL
      RELEVANCE: This model sets the stage for further investigations that might study
      the influence of different interventions on fracture healing in implant
      associated osteomyelitis. Future observational studies might also evaluate the
      histological properties of callus in patients with osteomyelitis.

PMID- 25981712
TI  - Orthopaedic Healthcare Worldwide: Using Clinical Practice Guidelines in Clinical
      Decision Making.

PMID- 25981713
TI  - Does Arthroplasty Provide Better Outcomes Than Internal Fixation At Mid- and Long
      term Followup? A Meta-analysis.
AB  - BACKGROUND: Arthroplasty has been shown to be superior regarding low risk of
      reoperation and better function score to internal fixation for treatment of
      displaced femoral neck fractures at short-term followup. However, there are
      unanswered questions regarding the efficacy of arthroplasty in the longer term
      compared with internal fixation. QUESTIONS/PURPOSES: We performed a meta-analysis
      comparing arthroplasty (hemiarthroplasty or THA) with internal fixation in
      patients with displaced femoral neck fractures with respect to (1) mortality, (2)
      reoperation, (3) functional recovery, and (4) complications, including only
      randomized trials with a minimum of 4 years followup. METHODS: Computerized
      databases, including PubMed (MEDLINE), EMBASE, Cochrane Register of Controlled
      Trials databases, and Web of ScienceTM were searched for studies published from
      the inception date for each database to March 2014. Eleven randomized controlled
      trials that compared arthroplasty (either hemiarthroplasty or THA) with internal
      fixation for treatment of patients with a femoral neck fracture were included in
      our analysis. The quality of the trials was assessed according to the Cochrane
      Handbook and meta-analyses were conducted using RevMan 5.2 software from the
      Cochrane Collaboration. The heterogeneity among studies was evaluated by the I
      squared index (I2) and publication bias was assessed using forest plots. RESULTS:
      There were no differences between the internal fixation and arthroplasty groups
      for patient mortality at mid-term (48.4% vs 46.8%) or long-term followup (83.2%
      vs 81.5%). Arthroplasty was associated with a lower risk of reoperation at mid
      term (7.2% vs 39.8%; relative risk [RR]=0.10; 95% CI, 0.06-0.07) and at long-term
      followup (14.3% vs 43.8%; RR=0.10; 95% CI, 0.06-0.07). Arthroplasty was
      associated with better functional recovery at mid-term followup (standard mean
      difference [SMD]=0.55; 95% CI, 0.02-1.09), whereas function at long-term followup
      (SMD=0.14; 95% CI, -0.35 to 0.62) was not different between the arthroplasty and
      internal fixation groups. There were no significant differences in subsequent
      ipsilateral fractures (1.5% vs 1.2%; RR=2.18; 95% CI, 0.32-14.67; p=0.42) and
      deep infections (2.7% vs 2.9%; RR=0.89; 95% CI, 0.40-2.01; p=0.78) between
      patients treated with arthroplasty and internal fixation. CONCLUSIONS: Based on
      our results, we found that compared with internal fixation, arthroplasty may
      result in a lower rate of subsequent reoperation at mid- and long-term followup,
      and better mid-term functional recovery. Future studies should investigate the
      mid- and long-term results of THAs compared with hemiarthroplasty.

PMID- 25981714
TI  - Extrinsic Muscle Forces Affect Ankle Loading Before and After Total Ankle
      Arthroplasty.
AB  - BACKGROUND: Joint loading conditions have an effect on the development and
      management of ankle osteoarthritis and on aseptic loosening after total ankle
      arthroplasty (TAA). Apart from body weight, compressive forces induced by muscle
      action may affect joint loading. However, few studies have evaluated the
      influence of individual muscles on the intraarticular pressure distribution in
      the ankle. QUESTION/PURPOSES: The purpose of this study was to measure
      intraarticular pressure distribution and, in particular, (1) to quantify the
      effect of individual muscle action on peak-pressure magnitude; and (2) to
      identify the location of the center of pressure in the weightbearing native
      ankles and ankles that had TAA. METHODS: Peak pressure and intraarticular center
      of pressure were quantified during force alterations of four muscle groups
      (peronei, tibialis anterior, tibialis posterior, and triceps surae) in 10
      cadaveric feet. The pressure was measured with a pressure sensitive array before
      and after implantation of a three-component mobile-bearing TAA prosthesis. Linear
      mixed-effects models were calculated and the y-intercept (b0) and the slope (b1)
      of the regression were used to quantify the size of the effect. RESULTS: Mean
      maximum peak pressures of 2 MPa (+/- 2.6 MPa) and 6.2 MPa (+/- 3.6 MPa) were
      measured for the native and TAA joint respectively. The triceps surae greatly
      affect the magnitude of peak pressure in the native ankle (slope b1 = 0.174; p =
      0.001) and TAA joint (slope b1 = 0.416; p = 0.001). Furthermore, the force of
      most muscles caused a posterior and lateral shift of the center of pressure in
      both conditions. CONCLUSIONS: Our results suggest that muscle force production
      has the potential to alter the pressure distribution in the native ankles and
      those with and TAA. CLINICAL RELEVANCE: Our study results help us to understand
      the effect of muscle forces on joint loading conditions which could be used in
      muscle training strategies and the design of better prosthetic components.
      Physical therapy or guided exercises may provide the potential to relieve areas
      in the joint that show signs of early osteoarthritis or reduce the contact stress
      on prosthetic components, potentially reducing the risk of TAA failure
      attributable to wear.

PMID- 25981715
TI  - Are Volar Locking Plates Superior to Percutaneous K-wires for Distal Radius
      Fractures? A Meta-analysis.
AB  - BACKGROUND: Distal radius fractures are common, costly, and increasing in
      incidence. Percutaneous K-wire fixation and volar locking plates are two of the
      most commonly used surgical treatments for unstable dorsally displaced distal
      radius fractures. However, there is uncertainty regarding which of these
      treatments is superior. QUESTIONS/PURPOSES: We performed a meta-analysis of
      randomized controlled trials to determine whether patients treated with volar
      locking plates (1) achieved better function (2) attained better wrist motion, (3)
      had better radiographic outcomes, and (4) had fewer complications develop than
      did patients treated with K-wires for dorsally displaced distal radius fractures.
      METHODS: We performed a comprehensive search of MEDLINE (inception to 2014,
      October Week 2), EMBASE (inception to 2014, Week 42), and the Cochrane Central
      Register of Controlled Trials to identify relevant randomized controlled trials;
      we supplemented these searches with manual searches. We included studies of
      extraarticular and intraarticular distal radius fractures. Adjunctive external
      fixation was acceptable as long as the intent was to use only K-wires where
      possible and external fixation was used in less than 25% of the procedures. We
      considered a difference in the DASH scores of 10 as the minimal clinically
      important difference. We performed quality assessment with the Cochrane Risk of
      Bias tool and evaluated the strength of recommendations using the Grades of
      Recommendation, Assessment, Development and Evaluation (GRADE) approach. Seven
      randomized trials with a total of 875 participants were included in the meta
      analysis. RESULTS: Patients treated with volar locking plates had slightly better
      function than did patients treated with K-wires as measured by their DASH scores
      at 3 months (mean difference [MD], 7.5; 95% CI, 4.4-10.6; p < 0.001) and 12
      months (MD, 3.8; 95% CI, 1.2-6.3; p = 0.004). Neither of these differences
      exceeded the a priori-determined threshold for clinical importance (10 points).
      There was a small early advantage in flexion and supination in the volar locking
      plate group (3.7 degrees  [95% CI, 0.3 degrees -7.1 degrees ; p = 0.04] and 4.1
      degrees  [95% CI, 0.6 degrees -7.6 degrees ; p = 0.02] greater, respectively) at
      3 months, but not at later followups (6 or 12 months). There were no differences
      in radiographic outcomes (volar tilt, radial inclination, and radial height)
      between the two interventions. Superficial wound infection was more common in
      patients treated with K-wires (8.2% versus 3.2%; RR = 2.6; p = 0.001), but
      otherwise no difference in complication rates was found. CONCLUSIONS: Despite the
      small number of studies and the limitations inherent in a meta-analysis, we found
      that volar locking plates show better DASH scores at 3- and 12-month followups
      compared with K-wires for displaced distal radius fractures in adults; however,
      these differences were small and unlikely to be clinically important. Further
      research is required to better delineate if there are specific radiographic,
      injury, or patient characteristics that may benefit from volar locking plates in
      the short term and whether there are any differences in long-term outcomes and
      complications. LEVEL OF EVIDENCE: Level I, therapeutic study.

PMID- 25981716
TI  - Frequent femoral neck osteolysis with Birmingham mid-head resection resurfacing
      arthroplasty in young patients.
AB  - BACKGROUND: Mid-head resection total hip resurfacing arthroplasty was promoted as
      an alternative to traditional total hip resurfacing for patients with poor
      femoral head bone quality or abnormal femoral head morphology, because those
      patients are at high risk of failure with traditional total hip resurfacing. It
      is a large-headed metal-on-metal device that uses a short, bone-conserving stem.
      Good performance of the implant has been reported at short-term followup, but no
      information on the implant performance in the mid- or long-term is available.
      QUESTIONS/PURPOSES: In this study, we report (1) on the mid-term implant
      survivorship and hip scores in a single nondesigner surgeon series. Because of
      the occurrence of femoral neck osteolysis and pseudotumor in a subgroup of
      patients, we also investigated the following: (2) Were there any preoperative
      parameters that are associated with osteolysis? (3) Could we differentiate the
      osteolysis group from the others on the basis of implant component sizes,
      positions, and radiologic parameters? (4) Could we differentiate the osteolysis
      group from the others on the basis of metal ion levels? METHODS: Between 2006 and
      2011, one surgeon performed a total of 49 Birmingham Mid-head Resection total hip
      resurfacing arthroplasties in 47 patients. The general indications for this
      procedure were young patients who were considered suitable for hip resurfacing
      arthroplasty but had avascular necrosis, large cysts, or severe deformity of the
      femoral head. Clinical followup including Oxford Hip Score (OHS) and UCLA hip
      scores were available preoperatively and at a mean of 6 years (range, 3-8 years)
      on all patients (100%), radiographic followup on 45 of 47 (96%), MRIs on 18
      (38%), and metal ion levels on 37 (79%). Mean age at surgery was 50 years.
      Spearman's correlation was used to test the association between femoral neck
      osteolysis and preoperative parameters, implant component sizes and positions,
      and blood metal ion levels. RESULTS: We found 100% survival. Patients' median OHS
      was 46 of 48 (range, 35-48) and UCLA 8 of 10 (range, 4-10). However, 16% of the
      hips (seven of 45) demonstrated osteolysis in the femoral neck. Of the
      preoperative parameters, the osteolysis was associated with low weight (r = 
      0.337, p = 0.031) and to a lesser degree with female sex (r = 0.275, p = 0.067).
      Radiologically, the osteolysis was strongly associated with the presence of a
      pseudotumor on MRI (r = 0.663, p = 0.004). We could not differentiate the
      osteolysis group from the rest of the cohort on the basis of the implant sizes or
      radiographic implant component positions. The cohort's median whole blood cobalt
      was 1.77 ppb (range, 0.18-10.27 ppb) and chromium 1.88 ppb (range 0.36-10.09
      ppb). There was no difference in the metal ion levels between the osteolysis
      group and the rest of the cohort. CONCLUSIONS: The high rate of silently
      developing femoral neck osteolysis associated with this implant is concerning and
      is expected to cause a high rate of failure at longer followup. We have
      instituted a program of annual clinical and radiologic followup for this group of
      patients. We have stopped implanting this device and recommend against its use.
      LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 25981718
TI  - Patient-specific anisotropic model of human trunk based on MR data.
AB  - There are many ways to generate geometrical models for numerical simulation, and
      most of them start with a segmentation step to extract the boundaries of the
      regions of interest. This paper presents an algorithm to generate a patient
      specific three-dimensional geometric model, based on a tetrahedral mesh, without
      an initial extraction of contours from the volumetric data. Using the information
      directly available in the data, such as gray levels, we built a metric to drive a
      mesh adaptation process. The metric is used to specify the size and orientation
      of the tetrahedral elements everywhere in the mesh. Our method, which produces
      anisotropic meshes, gives good results with synthetic and real MRI data. The
      resulting model quality has been evaluated qualitatively and quantitatively by
      comparing it with an analytical solution and with a segmentation made by an
      expert. Results show that our method gives, in 90% of the cases, as good or
      better meshes as a similar isotropic method, based on the accuracy of the volume
      reconstruction for a given mesh size. Moreover, a comparison of the Hausdorff
      distances between adapted meshes of both methods and ground-truth volumes shows
      that our method decreases reconstruction errors faster.

PMID- 25981719
TI  - Resisting the binarism of victim and agent: Critical reflections on 20 years of
      scholarship on young women and heterosexual practices in South African contexts.
AB  - The last 20 years have seen a proliferation of research, spurred by the
      imperatives of the HIV epidemic and reportedly high rates of gender-based
      violence, on heterosexual practices in the South African context. Research has
      focused on how poverty, age and gender within specific cultural contexts shape
      sexual agency and provide a context for unequal, coercive and violent practices
      for young women. This paper takes stock of what we currently 'know' about
      heterosex and critically reflects on the political and ideological effects of
      such research, specifically in the light of young women's agency. A primary
      concern is that efforts to address gender inequality and the normative gender
      practices that shape inequitable heterosexual practices may have functioned to
      reproduce the very discourses that underpin such inequalities. The paper
      'troubles' the victim-agency binarism as it has been played out in South African
      research on heterosex, raising concerns about how the research may reproduce
      gendered, classed and raced othering practices and discourses and bolstered
      regulatory and disciplinary responses to young women's sexualities. The paper
      argues for critical, feminist self-reflexivity that should extend to re-thinking
      methodologies entrenched in frameworks of authority and surveillance. 

PMID- 25981717
TI  - Different dynamin blockers interfere with distinct phases of synaptic endocytosis
      during stimulation in motoneurones.
AB  - KEY POINTS: Neurotransmitter release requires a tight coupling between synaptic
      vesicle exocytosis and endocytosis with dynamin being a key protein in that
      process. We used imaging techniques to examine the time course of endocytosis at
      mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded
      reporter of the synaptic vesicle cycle. We separated two sequential phases of
      endocytosis taking place during the stimulation train: early and late
      endocytosis. Freshly released synaptic vesicle proteins are preferentially
      retrieved during the early phase, which is very sensitive to dynasore, an
      inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at
      the plasma membrane before the stimulation are preferentially retrieved during
      the late phase, which is very sensitive to myristyl trimethyl ammonium bromide
      (MitMAB), an inhibitor of the dynamin-phospholipid interaction. ABSTRACT:
      Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter
      release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin
      (spH) transgenic mice, we have used imaging to study exo- and endocytosis
      occurring simultaneously during nerve stimulation. We observed two endocytosis
      components, which occur sequentially during stimulation. The early component of
      endocytosis apparently internalizes spH molecules freshly exocytosed. This
      component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In
      contrast, this early component was resistant to myristyl trimethyl ammonium
      bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid
      membranes. The late component of endocytosis is likely to internalize spH
      molecules that pre-exist at the plasma membrane before stimulation starts. This
      component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or
      other key endocytic proteins to phospholipid membranes. Our study suggests the co
      existence of two sequential synaptic endocytosis steps taking place during
      stimulation that are susceptible to pharmacological dissection: an initial step,
      preferentially sensitive to dynasore, that internalizes vesicular components
      immediately after they are released, and a MiTMAB-sensitive step that
      internalizes vesicular components pre-existing at the plasma membrane surface. In
      addition, we report that post-stimulus endocytosis also has several components
      with different sensitivities to dynasore and MiTMAB.

PMID- 25981720
TI  - Preparation for mass casualty incidents.
AB  - Mass casualty incidents are events where the number of injured patients exceeds
      the resources of the health care institution to the degree that care may not be
      available or may be limited for a portion of the casualties. Mass casualty
      incidents are increasing in frequency throughout the United States. Managing mass
      casualty incidents has not traditionally been part of the nursing curriculum;
      however, our changing world requires us to become educated and prepared to
      respond to these scenarios. This article focuses on intentional explosive
      disasters and the nursing and institutional response to these incidents. This
      information is of value to nursing professionals and other health care providers.

PMID- 25981721
TI  - Nonaccidental trauma: guidance for nurses in the pediatric intensive care unit.
AB  - Each year thousands of children are hospitalized for traumatic injuries
      associated with physical abuse. Nurses in the pediatric intensive care unit must
      be knowledgeable and skilled in caring for the physical, psychological,
      emotional, social, and developmental needs of such children and their families.
      This article provides direction for pediatric nurses working in the critical care
      setting. Specifically, it describes the nursing care of children in a pediatric
      intensive care unit where the mechanism of nonaccidental injury is blunt force to
      the head, abdomen, or musculoskeletal system, based on standards put forth by the
      American Association of Critical-Care Nurses. 

PMID- 25981722
TI  - Trauma in the geriatric population.
AB  - Injury in older adults is a looming public health crisis. This article provides a
      broad overview of geriatric trauma across the continuum of care. After a review
      of the epidemiology of geriatric trauma, optimal approaches to patient care are
      presented for triage and transport, trauma team activation and initial
      assessment, inpatient management, and injury prevention. Special emphasis is
      given to assessment of frailty, advanced care planning, and transitions of care. 

PMID- 25981723
TI  - Trauma resuscitation and monitoring: military lessons learned.
AB  - Over the past 13 years, the military health care system has made improvements
      that are associated with an unprecedented survival rate for severely injured
      casualties. Monitoring for indications of deterioration as the critically injured
      patient moves across the continuum of care is difficult given the limitations of
      routinely used vital signs. Research by both military and civilian researchers is
      revolutionizing monitoring, with an increased focus on noninvasive, continuous,
      dynamic measurements to provide earlier, more sensitive indications of the
      patient's perfusion status.

PMID- 25981724
TI  - Advances in cerebral monitoring for the patient with traumatic brain injury.
AB  - A brief overview of the most common invasive and noninvasive monitoring tools
      collectively referred to using the term "multimodal monitoring" is provided.
      Caring for the critically ill patient with traumatic brain injury requires
      careful monitoring to prevent or reduce secondary brain injury. Concurrent to the
      growth of the subspecialty of neurocritical care, there has been a concerted
      effort to discover novel mechanisms to monitor the physiology of brain injury.
      The past 2 decades have witnessed an exponential growth in neurologic monitoring
      in terms of intracranial pressure, blood flow, metabolism, oxygenation, advanced
      neuroimaging, and electrophysiology. 

PMID- 25981725
TI  - Considerations for neuroprotection in the traumatic brain injury population.
AB  - Traumatic brain injury can occur very quickly, but the sequelae of the injury can
      be life ending or life altering. Aside from prevention, the primary injury cannot
      be controlled; however, health care workers can influence the amount of secondary
      injury to the brain. This article describes potential neuroprotective methods,
      such as cooling, craniectomy, and medications, to help to save the brain. 

PMID- 25981726
TI  - Pain management in military trauma.
AB  - The wounded warrior requires immediate care, and at times, evacuation from
      injury. Care may be self-regulated, or may require more advanced care under the
      direction of medics or advanced practitioners, including physicians and surgeons.
      While survivability is the immediate priority, pain management has become a
      military initiative, recognizing that poor management of acute pain may lead to
      the development of chronic pain and post-traumatic stress disorder. This article
      reviews current initiatives used in current conflict situations, as well as those
      in continued care following initial stabilization. 

PMID- 25981727
TI  - Evidence-based Treatments for Military-related Posttraumatic Stress Disorder in a
      Veterans Affairs Setting.
AB  - Posttraumatic stress disorder (PTSD) can have a significant negative impact on
      the physical, emotional, and mental health of individuals. This article discusses
      the prevalence, risk factors, and diagnostic criteria for PTSD. Given the high
      incidence of PTSD in the Veteran population, much attention has been given to
      assessment and treatment issues. Treatment options for PTSD, including the 2 most
      effective treatments, prolonged exposure and cognitive processing therapy, are
      discussed. Special issues concerning the treatment of Veterans are also reviewed.

PMID- 25981728
TI  - Intimate partner violence: the role of nurses in protection of patients.
AB  - Intimate partner violence (IPV) is a worldwide epidemic that has been prevalent
      in society since biblical times. IPV affects women long after the abuse stops,
      with victims of IPV having generalized worsening of health, including depression
      and increased thoughts of suicide and suicide attempts. It is not uncommon for
      victims of IPV to be killed by their partner. Through regular screening and
      education clinicians can detect the violence before it is too late. Health care
      professionals have a unique opportunity to stop the cycle of abuse by
      intervening, promoting safety, and preventing the death of IPV victims. 

PMID- 25981729
TI  - Blast injury: impact on brain and internal organs.
AB  - Blast trauma can kill or injure by multiple different mechanisms, not all of
      which may be obvious on initial presentation. Patients injured by blast effects
      should be treated as having multisystem trauma and managed according to Advanced
      Trauma Life Support guidelines. For the most severely injured patients, damage
      control resuscitation should be practiced until definitive hemorrhage control has
      been achieved. Patients with blast injuries may present in mass-casualty episodes
      that can overwhelm local resources. This article reviews some specific injuries,
      as well as the importance of mild traumatic brain injury. The importance of
      rehabilitation is discussed. 

PMID- 25981730
TI  - The complex nature of trauma.

PMID- 25981731
TI  - Development of the Transferable Potentials for Phase Equilibria Model for
      Hydrogen Sulfide.
AB  - The transferable potentials for phase equilibria force field is extended to
      hydrogen sulfide. The pure-component and binary vapor-liquid equilibria with
      methane and carbon dioxide and the liquid-phase relative permittivity are used
      for the parametrization of the Lennard-Jones (LJ) and Coulomb interactions, and
      models with three and four interaction sites are considered. For the three-site
      models, partial point charges are placed on the sites representing the three
      atoms, while the negative partial charge is moved to an off-atom site for the
      four-site models. The effect of molecular shape is probed using either only a
      single LJ interaction site on the sulfur atom or adding sites also on the
      hydrogen atoms. This procedure results in four distinct models, but only those
      with three LJ sites can accurately reproduce all properties considered for the
      parametrization. These two are further assessed for predictions of the liquid
      phase structure, the lattice parameters and relative permittivity for the face
      centered-cubic solid, and the triple point. An effective balance between LJ
      interactions and the dipolar and quadrupolar terms of the first-order
      electrostatic interactions is struck in order to obtain a four-site model that
      describes the condensed-phase properties and the phase equilibria with high
      accuracy. 

PMID- 25981732
TI  - Recalibration of auditory phonemes by lipread speech is ear-specific.
AB  - Listeners quickly learn to label an ambiguous speech sound if there is lipread
      information that tells what the sound should be (i.e., phonetic recalibration
      Bertelson, Vroomen, & de Gelder (2003)). We report the counter-intuitive result
      that the same ambiguous sound can be simultaneously adapted to two opposing
      phonemic interpretations if presented in the left and right ear. This is strong
      evidence against the notion that phonetic recalibration involves an adjustment of
      abstract phoneme boundaries. It rather supports the idea that phonetic
      recalibration is closely tied to the sensory specifics of the learning context. 

PMID- 25981733
TI  - Philosophers' biased judgments persist despite training, expertise and
      reflection.
AB  - We examined the effects of framing and order of presentation on professional
      philosophers' judgments about a moral puzzle case (the "trolley problem") and a
      version of the Tversky & Kahneman "Asian disease" scenario. Professional
      philosophers exhibited substantial framing effects and order effects, and were no
      less subject to such effects than was a comparison group of non-philosopher
      academic participants. Framing and order effects were not reduced by a forced
      delay during which participants were encouraged to consider "different variants
      of the scenario or different ways of describing the case". Nor were framing and
      order effects lower among participants reporting familiarity with the trolley
      problem or with loss-aversion framing effects, nor among those reporting having
      had a stable opinion on the issues before participating the experiment, nor among
      those reporting expertise on the very issues in question. Thus, for these
      scenario types, neither framing effects nor order effects appear to be reduced
      even by high levels of academic expertise. 

PMID- 25981734
TI  - Differential Potential of Pharmacological PARP Inhibitors for Inhibiting Cell
      Proliferation and Inducing Apoptosis in Human Breast Cancer Cells.
AB  - BRCA1/2-mutant cells are hypersensitive to inactivation of poly(ADP-ribose)
      polymerase 1 (PARP-1). We recently showed that inhibition of PARP-1 by NU1025 is
      strongly cytotoxic for BRCA1-positive BT-20 cells, but not BRCA1-deficient SKBr-3
      cells. These results raised the possibility that other PARP-1 inhibitors,
      particularly those tested in clinical trials, may be more efficacious against
      BRCA1-deficient SKBr-3 breast cancer cells than NU1025. Thus, in the presented
      study the cytotoxicity of four PARP inhibitors under clinical evaluation
      (olaparib, rucaparib, iniparib and AZD2461) was examined and compared to that of
      NU1025. The sensitivity of breast cancer cells to the PARP-1 inhibition strongly
      varied. Remarkably, BRCA-1-deficient SKBr-3 cells were almost completely
      insensitive to NU1025, olaparib and rucaparib, whereas BRCA1-expressing BT-20
      cells were strongly affected by NU1025 even at low doses. In contrast, iniparib
      and AZD2461 were cytotoxic for both BT-20 and SKBr-3 cells. Of the four tested
      PARP-1 inhibitors only AZD2461 strongly affected cell cycle progression.
      Interestingly, the anti-proliferative and pro-apoptotic potential of the tested
      PARP-1 inhibitors clearly correlated with their capacity to damage DNA. Further
      analyses revealed that proteomic signatures of the two studied breast cancer cell
      lines strongly differ, and a set of 197 proteins was differentially expressed in
      NU1025-treated BT-20 cancer cells. These results indicate that BT-20 cells may
      harbor an unknown defect in DNA repair pathway(s) rendering them sensitive to
      PARP-1 inhibition. They also imply that therapeutic applicability of PARP-1
      inhibitors is not limited to BRCA mutation carriers but can be extended to
      patients harboring deficiencies in other components of the pathway(s).

PMID- 25981735
TI  - Pearls and pitfalls of imaging metastatic disease from pancreatic adenocarcinoma:
      a systematic review.
AB  - Pancreatic adenocarcinoma is a systemic disease due to the presence of metastatic
      disease at the time of diagnosis and local recurrence as well as distant
      metastatic disease after treatment in a majority of patients. Recognition of
      these metastatic sites may help in accurate staging and assessment of therapeutic
      response. The authors discuss and illustrate imaging findings of metastatic
      disease from pancreatic adenocarcinoma in different organ systems with emphasis
      on entities that can mimic metastatic pancreatic cancer. 

PMID- 25981736
TI  - Tuberculosis in evolution.

PMID- 25981738
TI  - Clinical application of whole-genome sequencing in patients with primary
      immunodeficiency.

PMID- 25981737
TI  - TNF-related apoptosis-inducing ligand (TRAIL) regulates midline-1, thymic stromal
      lymphopoietin, inflammation, and remodeling in experimental eosinophilic
      esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is an inflammatory disorder of the
      esophagus defined by eosinophil infiltration and tissue remodeling with resulting
      symptoms of esophageal dysfunction. TNF-related apoptosis-inducing ligand (TRAIL)
      promotes inflammation through upregulation of the E3 ubiquitin-ligase midline-1
      (MID1), which binds to and deactivates the catalytic subunit of protein
      phosphatase 2Ac, resulting in increased nuclear factor kappaB activation.
      OBJECTIVE: We sought to elucidate the role of TRAIL in EoE. METHODS: We used
      Aspergillus fumigatus to induce EoE in TRAIL-sufficient (wild-type) and TRAIL
      deficient (TRAIL(-/-)) mice and targeted MID1 in the esophagus with small
      interfering RNA. We also treated mice with recombinant thymic stromal
      lymphopoietin (TSLP) and TRAIL. RESULTS: TRAIL deficiency and MID1 silencing with
      small interfering RNA reduced esophageal eosinophil and mast cell numbers and
      protected against esophageal circumference enlargement, muscularis externa
      thickening, and collagen deposition. MID1 expression and nuclear factor kappaB
      activation were reduced in TRAIL(-/-) mice, whereas protein phosphatase 2Ac
      levels were increased compared with those seen in wild-type control mice. This
      was associated with reduced expression of CCL24, CCL11, CCL20, IL-5, IL-13, IL
      25, TGFB, and TSLP. Treatment with TSLP reconstituted hallmark features of EoE in
      TRAIL(-/-) mice and recombinant TRAIL induced esophageal TSLP expression in vivo
      in the absence of allergen. Post hoc analysis of gene array data demonstrated
      significant upregulation of TRAIL and MID1 in a cohort of children with EoE
      compared with that seen in controls. CONCLUSION: TRAIL regulates MID1 and TSLP,
      inflammation, fibrosis, smooth muscle hypertrophy, and expression of inflammatory
      effector chemokines and cytokines in experimental EoE.

PMID- 25981739
TI  - Peripheral blood eosinophilia and hypersensitivity reactions among patients
      receiving outpatient parenteral antibiotics.
AB  - BACKGROUND: Although drug-induced peripheral eosinophilia complicates
      antimicrobial therapy, little is known about its frequency and implications.
      OBJECTIVE: We aimed to determine the frequency and predictors of antibiotic
      induced eosinophilia and subsequent hypersensitivity reactions (HSRs). METHODS:
      We evaluated a prospective cohort of former inpatients receiving intravenous
      antibiotic therapy as outpatients with at least 1 differential blood count. We
      used multivariate Cox proportional hazards models with time-varying antibiotic
      treatment indicators to assess the effect of demographic data and antibiotic
      exposures on eosinophilia and subsequent HSRs, including documented rash, renal
      injury, and liver injury. Possible drug rash with eosinophilia and systemic
      symptoms (DRESS) syndrome cases were identified and manually validated. RESULTS:
      Of 824 patients (60% male; median age, 60 years; median therapy duration, 41
      days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of
      726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin,
      rifampin, and linezolid was associated with a higher hazard of having
      eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with
      eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n
      = 13). Patients with eosinophilia were significantly more likely to have rash
      (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P < .0001) and renal injury (HR,
      2.13; 95% CI, 1.36-3.33; P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92
      3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4
      (57%) were receiving vancomycin. CONCLUSIONS: Drug-induced eosinophilia is common
      with parenteral antibiotics. Although most patients with eosinophilia do not have
      an HSR, eosinophilia increases the hazard rate of having rash and renal injury.
      DRESS syndrome was more common than previously described.

PMID- 25981740
TI  - The risk factor age in normotensive patients with pulmonary embolism:
      Effectiveness of age in predicting submassive pulmonary embolism, cardiac injury,
      right ventricular dysfunction and elevated systolic pulmonary artery pressure in
      normotensive pulmonary embolism patients.
AB  - INTRODUCTION: Right ventricular dysfunction (RVD), submassive pulmonary embolism
      (PE), elevated systolic pulmonary artery pressure (sPAP), elevated cardiac
      troponin I (cTnI) and old age are well-known risk factors for poor outcome in
      acute normotensive PE. The aim of this analysis was to calculate age cut-off
      values to predict submassive PE, cardiac injury, RVD and elevated sPAP in
      normotensive PE patients. METHODS: Retrospective analysis of clinical,
      laboratory, radiological and echocardiographic data of normotensive PE patients
      (2006-2011) was performed. Receiver operating characteristic (ROC) curves and
      Youden indexes were used to test the effectiveness of using patients' ages at the
      PE event to predict a submassive PE, cardiac injury (elevated cTnI >0.1ng/ml),
      RVD and elevated sPAP (>30mmHg) in normotensive PE patients and to calculate
      optimal cut-off values. Patients >76years were compared to those aged <=76years.
      RESULTS: 129 normotensive PE patients (59.7% women) met the inclusion criteria
      and were included in this analysis. The optimal cut-off value for patient ages to
      predict submassive PE, cardiac injury (elevated cTnI >0.1ng/ml), RVD and elevated
      sPAP (>30mmHg) was 76.5, 81.5, 66.5 and 66.5years, respectively, with moderate
      effectiveness (AUC 0.69, 0.58, 0.71 and 0.69, respectively). Patients >76years
      old had higher percentages of submassive PE (91.1% vs. 63.1%, P=0.000680), RVD
      (91.1% vs. 58.3%, P=0.000119), sPAP (42.64+/-16.70 vs. 29.24+/-17.56mmHg,
      P=0.000044) and cTnI (0.22+/-0.40 vs. 0.10+/-0.25ng/ml, P=0.00488). CONCLUSIONS:
      Age is an important prognostic factor in acute normotensive PE. In addition to
      cTn and RVD, age should be taken into account in determining the risk
      stratification for acute PE.

PMID- 25981741
TI  - Construct validity of the Groningen Frailty Indicator established in a large
      sample of home-dwelling elderly persons: Evidence of stability across age and
      gender.
AB  - BACKGROUND: The primary objective of the present study was to evaluate the
      validity of the Groningen Frailty Indicator (GFI) in a sample of Dutch elderly
      persons participating in LifeLines, a large population-based cohort study.
      Additional aims were to assess differences between frail and non-frail elderly
      and examine which individual characteristics were associated with frailty.
      METHODS: By December 2012, 5712 elderly persons were enrolled in LifeLines and
      complied with the inclusion criteria of the present study. Mann-Whitney U or
      Kruskal-Wallis tests were used to assess the variability of GFI-scores among
      elderly subgroups that differed in demographic characteristics, morbidity,
      obesity, and healthcare utilization. Within subgroups Kruskal-Wallis tests were
      also used to examine differences in GFI-scores across age groups. Multivariate
      logistic regression analyses were performed to assess associations between
      individual characteristics and frailty. RESULTS: The GFI discriminated between
      subgroups: statistically significantly higher GFI-median scores (interquartile
      range) were found in e.g. males (1 [0-2]), the oldest old (2 [1-3]), in elderly
      who were single (1 [0-2]), with lower socio economic status (1 [0-3]), with
      increasing co-morbidity (2 [1-3]), who were obese (2 [1-3]), and used more
      healthcare (2 [1-4]). Overall age had an independent and statistically
      significant association with GFI scores. Compared with the non-frail, frail
      elderly persons experienced statistically significantly more chronic stress and
      more social/psychological related problems. In the multivariate logistic
      regression model, psychological morbidity had the strongest association with
      frailty. CONCLUSION: The present study supports the construct validity of the GFI
      and provides an insight in the characteristics of (non)frail community-dwelling
      elderly persons participating in LifeLines.

PMID- 25981744
TI  - Genetic predisposition and its impact on natural history of idiopathic acute and
      acute recurrent pancreatitis in children.
AB  - BACKGROUND: Genetic predisposition in paediatric idiopathic acute, acute
      recurrent pancreatitis and its consequences are unknown. We studied frequency of
      genetic markers in acute, acute recurrent, chronic pancreatitis and their impact
      on natural history. METHODS: Over a period of 2 years 68 consecutive children
      with pancreatitis (35.3% acute, 32.3% acute recurrent, 32.3% chronic) and 25
      controls were recruited in a single centre. Common mutations for serine-protease
      inhibitor (SPINK1 N34S), protease-inhibitor (PRSS1 R122H) and cystic fibrosis
      transmembrane conductance regulator (CFTR DeltaF508, 5T) were analysed. RESULTS:
      Mean age was 13.4+/-2.5 years. Overall, 30 cases (SPINK1 N34S n=26, CFTR 5T n=4)
      and 1 control (SPINK1 N34S) had mutations (p=0.0001). The prevalence of SPINK1
      N34S mutation was similar in chronic and acute recurrent pancreatitis (45%). Six
      children with severe acute pancreatitis had SPINK1 N34S mutations (25%, p<0.05),
      and 4 were homozygous. On follow-up 5 acute pancreatitis patients with mutations
      and 1 without mutations developed chronic pancreatitis (p=0.004); 8 cases of
      acute recurrent pancreatitis progressed to chronic pancreatitis (38%); of these
      66.7% had mutations vs. 16.7% who did not (p=0.03). CONCLUSIONS: Almost 50% of
      idiopathic chronic, acute recurrent and 33% of acute pancreatitis in children are
      genetically predisposed. Presence of genetic mutations in acute and recurrent
      acute pancreatitis increases the risk of developing chronic pancreatitis.

PMID- 25981742
TI  - A standardized randomized 6-month aerobic exercise-training down-regulated pro
      inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon
      growth-related genes.
AB  - There is considerable support for the view that aerobic exercise may confer
      cognitive benefits to mild cognitively impaired elderly persons. However, the
      biological mechanisms mediating these effects are not entirely clear. As a
      preliminary step towards informing this gap in knowledge, we enrolled older
      adults confirmed to have mild cognitive impairment (MCI) in a 6-month exercise
      program. Male and female subjects were randomized into a 6-month program of
      either aerobic or stretch (control) exercise. Data collected from the first 10
      completers, aerobic exercise (n=5) or stretch (control) exercise (n=5), were used
      to determine intervention-induced changes in the global gene expression profiles
      of the aerobic and stretch groups. Using microarray, we identified genes with
      altered expression (relative to baseline values) in response to the 6-month
      exercise intervention. Genes whose expression were altered by at least two-fold,
      and met the p-value cutoff of 0.01 were inputted into the Ingenuity Pathway
      Knowledge Base Library to generate gene-interaction networks. After a 6-month
      aerobic exercise-training, genes promoting inflammation became down-regulated,
      whereas genes having anti-inflammatory properties and those modulating immune
      function or promoting neuron survival and axon growth, became up-regulated (all
      fold change>=+/-2.0, p<0.01). These changes were not observed in the stretch
      group. Importantly, the differences in the expression profiles correlated with
      significant improvement in maximal oxygen uptake (VO2max) in the aerobic program
      as opposed to the stretch group. We conclude that three distinct cellular
      pathways may collectively influence the training effects of aerobic exercise in
      MCI subjects. We plan to confirm these effects using rt-PCR and correlate such
      changes with the cognitive phenotype. 

PMID- 25981745
TI  - Dysregulation of clathrin promotes thyroid cell growth and contributes to
      multinodular goiter pathogenesis.
AB  - A germline mutation (A339V) in thyroid transcription factor-1 (TITF1/NKX2.1) was
      shown to be associated with multinodular goiter (MNG) and papillary thyroid
      carcinoma (PTC) pathogenesis. The overexpression of A339V TTF1 significantly
      promoted hormone-independent growth of the normal thyroid cells, representing a
      cause of MNG and/or PTC. Nevertheless, the underlying mechanism still remains
      unclear. In this study, we used liquid chromatography (LC)-tandem mass
      spectrometry (MS/MS)-based shotgun proteomics comparing the global protein
      expression profiles of normal thyroid cells (PCCL3) that overexpressed the wild
      type or A339V TTF1 to identify key proteins implicated in this process. Proteomic
      pathway analysis revealed that the aberrant activation of epidermal growth factor
      (EGF) signaling is significantly associated with the overexpression of A339V TTF1
      in PCCL3, and clathrin heavy chain (Chc) is the most significantly up-regulated
      protein of the pathway. Intriguingly, dysregulated Chc expression facilitated a
      nuclear accumulation of pStat3, leading to an enhanced cell proliferation of the
      A339V clones. Down-regulation and abrogation of Chc-mediated cellular
      trafficking, respectively, by knocking-down Chc and ectopic expression of a
      dominant-negative (DN) form of Chc could significantly reduce the nuclear pStat3
      and rescue the aberrant cell proliferation of the A339V clones. Subsequent
      expression analysis further revealed that CHC and pSTAT3 are co-overexpressed in
      66.7% (10/15) MNG. Taken together, our results suggest that the A339V TTF1 mutant
      protein up-regulates the cellular expression of Chc, resulting in a constitutive
      activation of Stat3 pathway, and prompting the aberrant growth of thyroid cells.
      This extensive growth signal may promote the development of MNG. 

PMID- 25981743
TI  - Trans-synaptic zinc mobilization improves social interaction in two mouse models
      of autism through NMDAR activation.
AB  - Genetic aspects of autism spectrum disorders (ASDs) have recently been
      extensively explored, but environmental influences that affect ASDs have received
      considerably less attention. Zinc (Zn) is a nutritional factor implicated in
      ASDs, but evidence for a strong association and linking mechanism is largely
      lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues
      social interaction in two independent mouse models of ASD. In mice lacking
      Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation
      induced by clioquinol (a Zn chelator and ionophore) improves social interaction.
      Postsynaptic Zn is mainly derived from presynaptic pools and activates NMDA
      receptors (NMDARs) through postsynaptic activation of the tyrosine kinase Src.
      Clioquinol also improves social interaction in mice haploinsufficient for the
      transcription factor Tbr1, which accompanies NMDAR activation in the amygdala.
      These results suggest that trans-synaptic Zn mobilization induced by clioquinol
      rescues social deficits in mouse models of ASD through postsynaptic Src and NMDAR
      activation. 

PMID- 25981747
TI  - Management of immune-mediated cytopenias in pregnancy.
AB  - Immune-mediated cytopenias are a well-described complication of pregnancy.
      Appropriate recognition and treatment are important in order to limit maternal
      and fetal morbidity and mortality. First line treatment options are fairly well
      established for these entities. Refractory disease may be difficult to manage
      because treatment choices are limited by known or unestablished risk to the
      fetus. While the use of new agents, such as romiplostim and rituximab, has been
      reported, their safety in pregnancy is not known. This article summarizes immune
      cytopenias seen in pregnant patients, and it also discusses management of these
      cytopenias, and provides practical strategies for the treatment of these
      challenging conditions. 

PMID- 25981746
TI  - Clostridium sordellii genome analysis reveals plasmid localized toxin genes
      encoded within pathogenicity loci.
AB  - BACKGROUND: Clostridium sordellii can cause severe infections in animals and
      humans, the latter associated with trauma, toxic shock and often-fatal
      gynaecological infections. Strains can produce two large clostridial cytotoxins
      (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile,
      Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin
      production remains uncharacterised. RESULTS: Phylogenetic analysis of the genome
      sequences of 44 strains isolated from human and animal infections in the UK, US
      and Australia placed the species into four clades. Although all strains
      originated from animal or clinical disease, only 5 strains contained LCC genes: 4
      strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin
      positive strains were found within one clade. Where present, tcsL and tcsH were
      localised in a pathogenicity locus, similar to but distinct from that present in
      C. difficile. In contrast to C. difficile, where the LCCs are chromosomally
      localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our
      data suggest gain and loss of entire toxigenic plasmids in addition to horizontal
      transfer of the pathogenicity locus. A high quality, annotated sequence of
      ATCC9714 reveals many putative virulence factors including neuraminidase,
      phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are
      highly conserved between all strains studied. CONCLUSIONS: Genome analysis of C.
      sordellii reveals that the LCCs, the major virulence factors, are localised on
      plasmids. Many strains do not contain the LCC genes; it is probable that in
      several of these cases the plasmid has been lost upon laboratory subculture. Our
      data are consistent with LCCs being the primary virulence factors in the majority
      of infections, but LCC-negative strains may precipitate certain categories of
      infection. A high quality genome sequence reveals putative virulence factors
      whose role in virulence can be investigated.

PMID- 25981748
TI  - The real reason for having a meibomian lipid layer covering the outer surface of
      the tear film - A review.
AB  - This review critically evaluates a broad range of literature in order to show the
      relationship between meibum, tear lipids and the tear film lipid layer (TFLL).
      The relationship of meibum composition to dry eye syndrome is briefly discussed.
      The review also explores the interactions between aqueous and the TFLL by
      examining the correlations between meibomian lipids and lipids extracted from
      whole tears, and by considering protein adsorption to the TFLL from the aqueous.
      Although it is clear to the authors that a normal tear film resists evaporation,
      an emerging idea from the literature is that the main purpose of the TFLL is to
      allow the spread of the tear film and to prevent its collapse onto the ocular
      surface, rather than to be an evaporative blanket. Current models on the possible
      structure of the TFLL are also examined.

PMID- 25981749
TI  - Expression characterization, genomic structure and function analysis of fish
      ubiquitin-specific protease 18 (USP18) genes.
AB  - In mammals, USP18 (ubiquitin-specific protease 18) is an interferon (IFN)
      inducible protein and plays a role in regulation of IFN response upon viral
      infection. In this study, we first cloned a USP18 homologous gene from virally
      infected crucian carp (Carassius auratus) blastula embryonic (CAB) cells, and
      later found in other fish species including zebrafish. All fish USP18 genes have
      10 exons and 9 introns comparable to 11 exons and 10 introns in non-fish
      vertebrates. Expression analysis revealed that fish USP18 was significantly
      induced in vitro and in vivo by IFN and IFN stimuli. Using promoter-driven
      luciferase reporter assay system to explore the molecular mechanism underlying
      fish USP18 expression, fish USP18 was identified as a typical interferon (IFN)
      stimulated gene (ISG). Intracellular poly(I:C)-triggered zebrafish USP18
      expression was regulated through RLR-IFN pathway, which was consistent with the
      fact that fish USP18 gene promoter contained two typical IFN-stimulated response
      elements (ISREs). Further mutation assays revealed that the distant ISRE motif
      primarily contributed to the induction of zebrafish USP18 by fish IFN and IFN
      stimuli. Functionally, fish USP18 inhibited poly(I:C)- and IFN-triggered
      activation of a common ISRE-containing promoter, and attenuated transcriptional
      expression of some ISGs including Stat1 and PKZ by recombinant IFN. Finally, we
      found that fish USP18 protein was expressed in cytoplasm and exhibited an ability
      to interact with ISG15. These results indicate that fish USP18 likely exerts its
      function similar to mammalian homologs. 

PMID- 25981750
TI  - Elevated serum monocyte chemoattractant protein-1 levels and its genetic
      polymorphism is associated with diabetic retinopathy in Chinese patients with
      Type 2 diabetes.
AB  - AIM: Previous studies have reported that monocyte chemoattractant protein-1 (MCP
      1) is involved in inflammatory and metabolic diseases. The purpose of this study
      is to investigate the role of MCP-1 in the pathogenesis of diabetic retinopathy
      (DR) in Han Chinese patients with Type 2 diabetes. METHODS: Serum levels of MCP-1
      protein in patients classified as diabetic without retinopathy (DWR) and DR,
      including NPDR and PDR, were assayed by enzyme-linked immunosorbent assay.
      Genomic DNA from 198 DWR patients, 176 NPDR patients and 143 PDR patients were
      genotyped by using a PCR restriction fragment length polymorphism (PCR-RFLP)
      assay. RESULTS: MCP-1 serum levels were significantly higher in NPDR and PDR
      patients than in the DWR patients. The frequencies of the GG genotype and G
      allele of the single nucleotide polymorphism (SNP) were significantly increased
      in DR patients compared with DWR patients. Further subgroup analysis was
      performed to test whether there was an association between the PDR or NPDR and
      DWR groups. Significantly higher frequencies of the GG genotype and G allele were
      observed in PDR and NPDR patients compared with DWR patients. Furthermore, the 25
      patients with PDR were divided into three groups according to the genotype of the
      tested SNP. The expression of the MCP-1 gene was higher in the GG genotype group
      compared with the other two groups. CONCLUSIONS: The results suggested that the 
      2518 GG genotype and G allele of MCP-1 are associated with an increased risk of
      PDR in the Chinese Han population. This polymorphism may influence the expression
      of the MCP-1 gene, which may play an important role in the pathogenesis of DR.

PMID- 25981751
TI  - pH-triggered drug release from biodegradable microwells for oral drug delivery.
AB  - Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their
      application as an oral drug delivery system using the amorphous sodium salt of
      furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication
      of microwells with an inner diameter of 240 MUm and a height of 100 MUm. The
      microwells were filled with ASSF using a modified screen printing technique,
      followed by coating of the microwell cavities with a gastro-resistant lid of
      Eudragit(r) L100. The release behavior of ASSF from the coated microwells was
      investigated using a MU-Diss profiler and a UV imaging system, and under
      conditions simulating the changing environment of the gastrointestinal tract.
      Biorelevant gastric medium (pH 1.6) was employed, after which a change to
      biorelevant intestinal release medium (pH 6.5) was carried out. Both MU-Diss
      profiler and UV imaging release experiments showed that sealing of microwell
      cavities with an Eudragit(r) layer prevented drug release in biorelevant gastric
      medium. An immediate release of the ASSF from coated microwells was observed in
      the intestinal medium. This pH-triggered release behavior demonstrates the future
      potential of PLLA microwells as a site-specific oral drug delivery system. 

PMID- 25981752
TI  - Fabrication and initial testing of the MUDBS: a novel Deep Brain Stimulation
      electrode with thousands of individually controllable contacts.
AB  - High frequency electrical stimulation of deep brain structures such as the
      subthalamic nucleus in Parkinson's disease or thalamus for essential tremor is
      used clinically to reduce symptom severity. Deep brain stimulation activates
      neurons in specific brain structures and connection pathways, overriding aberrant
      neural activity associated with symptoms. While optimal deep brain stimulation
      might activate a particular neural structure precisely, existing deep brain
      stimulation can only generate roughly-spherical regions of activation that do not
      overlap with any target anatomy. Additionally, side effects linked to stimulation
      may be the result of limited control over placement of stimulation and its
      subsequent spread out of optimal target boundaries. We propose a novel lead with
      thousands of individually controllable contacts capable of asymmetric stimulation
      profiles. Here we outline the design motivation, manufacturing process, and
      initial testing of this new electrode design, placing it on track for further
      directional stimulation studies. 

PMID- 25981754
TI  - Designing drugs that overcome antibacterial resistance: where do we stand and
      what should we do?
AB  - INTRODUCTION: In recent years, infections caused by multidrug-resistant bacterial
      pathogens have become a huge issue to public healthcare systems. Indeed, the
      misuse of antibiotics has led to, over the past 30 years, the emergence of a
      number of resistant bacterial strains including Staphylococcus aureus, Neisseria
      gonorrhoeae, Escherichia coli and Mycobacterium tuberculosis. Unfortunately,
      efforts to produce new antibiotics have not been sufficient to cope with the
      emergence of these new antibiotic-resistant (AR) strains. AREAS COVERED: There is
      an urgent need to invent and employ unconventional strategies for antimicrobial
      drug development to tackle the rising global threats imposed by the spread of
      antimicrobial resistance. Herein, the authors discuss these novel design
      strategies and provide their expert perspective on the subject. EXPERT OPINION:
      To deal with the growing threat of AR, it is important to cut down the use of
      antibiotics to the very minimum to diminish the risk of unknown drug-resistant
      bacteria and increase antibacterial vaccination programs. Furthermore, it is
      important to develop new classes of antibiotics that can deal with multidrug
      resistant bacterial pathogens.

PMID- 25981753
TI  - Sudden cardiac death rates in an Australian population: a data linkage study.
AB  - OBJECTIVE: The aim of the present study was to develop criteria to identify
      sudden cardiac death (SCD) and estimate population rates of SCD using
      administrative mortality and hospital morbidity records in Western Australia.
      METHODS: Four criteria were developed using place, death within 24 h, principal
      and secondary diagnoses, underlying and associated cause of death, and/or
      occurrence of a post mortem to identify SCD. Average crude, age-standardised and
      age-specific rates of SCD were estimated using population person-linked
      administrative data. RESULTS: In all, 9567 probable SCDs were identified between
      1997 and 2010, with one-third aged >= 35 years having no prior admission for
      cardiovascular disease. SCD was more frequent in men (62.1%). The estimated
      average annual crude SCD rate for the period was 34.6 per 100 000 person-years
      with an average annual age-standardised rate of 37.8 per 100 000 person-years.
      Age-specific standardised rates were 1.1 per 100 000 person-years and 70.7 per
      100 000 person-years in people aged 1-34 and >= 35 years, respectively. Ischaemic
      heart disease (IHD) was recorded as the underlying cause of death in
      approximately 80% of patients aged >= 35 years, followed by valvular heart
      disease and heart failure. IHD was the most common cause of death in those aged 1
      34 years, followed by unspecified cardiomyopathy and dysrhythmias. CONCLUSIONS:
      Administrative morbidity and mortality data can be used to estimate rates of SCD
      and therefore provide a suitable methodology for monitoring SCD over time. The
      findings highlight the magnitude of SCD and its potential for public health
      prevention.

PMID- 25981755
TI  - Changes in Family Relationships among Substance Abusing Runaway Adolescents: A
      Comparison between Family and Individual Therapies.
AB  - Eligible adolescents (12-17 years old) were recruited from a short-term crisis
      shelter for runaway adolescents in a large Midwestern city. Adolescents (N = 179)
      were randomly assigned to Ecologically-Based Family Therapy (EBFT, n = 61), the
      Community Reinforcement Approach (CRA, n = 57), or brief Motivational Enhancement
      Therapy (MET, n = 61) with the primary focus on substance abuse. A significant
      increase in perceived family cohesion and a significant reduction in perceived
      family conflict were found among all treatment conditions from baseline to the 24
      month follow-up. Adolescents who received EBFT demonstrated more improvement in
      family cohesion after treatment than those who received CRA or MET, and more
      reduction in family conflict during treatment than those who received MET. 

PMID- 25981756
TI  - Analytical Method for Measuring Cosmogenic (35)S in Natural Waters.
AB  - Cosmogenic sulfur-35 in water as dissolved sulfate ((35)SO4) has successfully
      been used as an intrinsic hydrologic tracer in low-SO4, high-elevation basins.
      Its application in environmental waters containing high SO4 concentrations has
      been limited because only small amounts of SO4 can be analyzed using current
      liquid scintillation counting (LSC) techniques. We present a new analytical
      method for analyzing large amounts of BaSO4 for (35)S. We quantify efficiency
      gains when suspending BaSO4 precipitate in Inta-Gel Plus cocktail, purify BaSO4
      precipitate to remove dissolved organic matter, mitigate interference of radium
      226 and its daughter products by selection of high purity barium chloride, and
      optimize LSC counting parameters for (35)S determination in larger masses of
      BaSO4. Using this improved procedure, we achieved counting efficiencies that are
      comparable to published LSC techniques despite a 10-fold increase in the SO4
      sample load. (35)SO4 was successfully measured in high SO4 surface waters and
      groundwaters containing low ratios of (35)S activity to SO4 mass demonstrating
      that this new analytical method expands the analytical range of (35)SO4 and
      broadens the utility of (35)SO4 as an intrinsic tracer in hydrologic settings. 

PMID- 25981757
TI  - Effects of an anabolic steroid (Durateston) on testicular angiogenesis in
      peripubertal stallions.
AB  - The aim of this study was to determine the effect of the anabolic steroid
      testosterone on the testicular vascularization, angiogenesis and expression of
      angiogenic factors, and their receptors in testes of peripubertal stallions.
      Seven peripubertal stallions were treated with Durateston and castrated either 4
      (treatment group 1 [TG1]) or 12 weeks (TG2) after the last injection. The
      castration of seven untreated control stallions (control group [CG]) took place
      within the same time. In the testicular specimens, volume density (VD), numerical
      density (ND), and area of vessels were determined morphometrically.
      Immunohistochemically, the expression of vascular endothelial growth factor
      (VEGF) and its receptor VEGF-R2; angiopoietin 2 (Ang2) and its receptor Tie2 as
      well as of transforming growth factor alpha (TGF-alpha) was investigated.
      Morphometrically, the VD of TG1 (P = 0.000) and TG2 (P = 0.001) vessels and the
      ND of arterioles and venules and capillaries were higher (TG1, TG2: P < 0.05),
      and the area of capillary cross sections was smaller (TG1, TG2: P < 0.05) than
      that in the CG. Compared to TG2 horses, TG1 animals showed a higher (P < 0.05) VD
      and ND of vascular structures and a smaller (P < 0.05) area of capillary cross
      sections. In numerous vascular structures, especially of TG1, the TGF-alpha and,
      to a less extent, the Ang2 and VEGF-R2 expression was significantly higher (P <
      0.05) than that in the CG. Sertoli cells in TG2 were characterized by a
      significantly higher expression (P < 0.05) of VEGF-R2 than in the CG. In summary,
      the most and smallest vessels could be detected in the testes of TG1. Most likely
      this is explainable by the highest expression of some angiogenic factors (TGF
      alpha, Ang2) and receptors (VEGF-R2) investigated. This expression behavior may
      be stimulated by testosterone. As a significant decrease of morphometric
      parameters could be detected in TG2 compared to TG1, the stimulatory effect of
      testosterone seems to be temporary.

PMID- 25981759
TI  - Subhepatic appendicitis masquerading as acute cholecystitis: a lesson learnt!

PMID- 25981760
TI  - Comparison of myocardial F-18 FDG uptake between overnight and non-overnight
      fasting in non-diabetic healthy subjects.
AB  - PURPOSE: To evaluate whether an overnight or non-overnight fast for suppressing
      physiological FDG uptake by the myocardium is better in non-diabetic healthy
      subjects before F-18 FDG PET/CT studies. MATERIALS AND METHODS: One hundred two
      subjects who underwent whole-body F-18 FDG PET/CT for routine health checkups
      were retrospectively reviewed. For quantitative assessment, a region of interest
      was drawn around the entire left ventricle visible in the axial view containing
      the highest visual uptake in order to measure the maximum standardized uptake
      value (SUV max). FDG uptake in the myocardium was visually graded as follows:
      grade 0 = minimal, 1 = mostly minimal or mild, 2 = mostly intense or moderate,
      and 3 = homogeneously intense. Adequate suppression of myocardial uptake was
      quantitatively defined as a SUV max <= 5.0 and grade 0 by visual assessment.
      RESULTS: With regard to the SUV max, myocardial uptake was not different between
      the overnight and the non-overnight fasting subjects (P = 0.753). In subjects who
      had adequate suppression of myocardial uptake, no significant difference was
      observed between the overnight and non-overnight fasting subjects either in terms
      of visual or quantitative assessment (P = 0.539 and P = 0.678, respectively).
      CONCLUSION: Both overnight and non-overnight fasts are not adequate for
      suppressing the physiological uptake of FDG by the myocardium.

PMID- 25981761
TI  - Characterizing cognitive impairment in multiple sclerosis: an essential step
      towards prediction and prevention.

PMID- 25981763
TI  - Immunohistochemistry relative to gravity: a simple method to retain information
      about gravity for immunolocalization and histochemistry.
AB  - We describe a simple method to preserve information about a plant organ's
      orientation relative to the direction of the gravity vector during sample
      processing for immunolocalization or histochemical analysis of cell biological
      processes. This approach has been used in gravity stimulated roots of Arabidopsis
      thaliana and Zea mays to study PIN3 relocalization, study the asymmetrical
      remodeling of the actin network and the cortical microtubule array, and to reveal
      the asymmetrical expression of the auxin signaling reporter DR5::GUS. This method
      enables the rapid analysis of a large number of samples from a variety of
      genotypes, as well as from tissue that may be too thick for microscopy in live
      plants. 

PMID- 25981762
TI  - Four-dimensional MRI using three-dimensional radial sampling with respiratory
      self-gating to characterize temporal phase-resolved respiratory motion in the
      abdomen.
AB  - PURPOSE: To develop a four-dimensional MRI (4D-MRI) technique to characterize the
      average respiratory tumor motion for abdominal radiotherapy planning. METHODS: A
      continuous spoiled gradient echo sequence was implemented with 3D radial
      trajectory and 1D self-gating for respiratory motion detection. Data were
      retrospectively sorted into different respiratory phases based on their temporal
      locations within a respiratory cycle, and each phase was reconstructed by means
      of a self-calibrating CG-SENSE program. Motion phantom, healthy volunteer and
      patient studies were performed to validate the respiratory motion detected by the
      proposed method against that from a 2D real-time protocol. RESULTS: The proposed
      method successfully visualized the respiratory motion in phantom and human
      subjects. The 4D-MRI and real-time 2D-MRI yielded comparable superior-inferior
      (SI) motion amplitudes (intraclass correlation = 0.935) with up-to one pixel mean
      absolute differences in SI displacements over 10 phases and high cross
      correlation between phase-resolved displacements (phantom: 0.985; human: 0.937
      0.985). Comparable anterior-posterior and left-right displacements of the tumor
      or gold fiducial between 4D and real-time 2D-MRI were also observed in the two
      patients, and the hysteresis effect was shown in their 3D trajectories.
      CONCLUSION: We demonstrated the feasibility of the proposed 4D-MRI technique to
      characterize abdominal respiratory motion, which may provide valuable information
      for radiotherapy planning.

PMID- 25981765
TI  - Quantification of root gravitropic response using a constant stimulus feedback
      system.
AB  - Numerous software packages now exist for quantifying root growth responses, most
      of which analyze a time resolved sequence of images ex post facto. However, few
      allow for the real-time analysis of growth responses. The system in routine use
      in our lab allows for real-time growth analysis and couples this to positional
      feedback to control the stimulus experienced by the responding root. This
      combination allows us to overcome one of the confounding variables in studies of
      root gravity response. Seedlings are grown on standard petri plates attached to a
      vertical rotating stage and imaged using infrared illumination. The angle of a
      particular region of the root is determined by image analysis, compared to the
      prescribed angle, and any corrections in positioning are made by controlling a
      stepper motor. The system allows for the long-term stimulation of a root at a
      constant angle and yields insights into the gravity perception and transduction
      machinery not possible with other approaches. 

PMID- 25981764
TI  - A flat embedding method to orient thin biological samples for sectioning.
AB  - Microscopy is an important tool used for biological research and has played a
      crucial role toward understanding of cellular mechanisms and protein function.
      However, specific steps in processing of biological samples for microscopy
      warrant improvements to consistently generate data that can more reliably help in
      explaining mechanisms underlying complex biological phenomenon. Due to their
      small and fragile nature, some biological specimens such as Arabidopsis thaliana
      roots are vulnerable to damage during long sample preparation steps. Moreover,
      when specimens with a small diameter (typically less than 100 MUm) are embedded
      in conventional silicone mold or capsule embedding, it is not only difficult to
      locate their orientation inside the capsule but also a challenge to obtain good
      median longitudinal sections. Specimen orientation in particular is crucial
      because understanding certain plant biological processes such as gravitropism
      rely on precisely knowing spatial information of cells and tissues of the plant
      organ being studied. Here we present a simple embedding technique to properly
      orient small plant organs so that the desired sectioning plane is achieved. This
      method is also inexpensive and can be accomplished with only minimal equipment
      and supplies. 

PMID- 25981766
TI  - Analysis of gravitropic setpoint angle control in Arabidopsis.
AB  - The history of research on gravitropism has been largely confined to the primary
      root-shoot axis and to understanding how the typically vertical orientation
      observed there is maintained. Many lateral organs are gravitropic too and are
      often held at specific non-vertical angles relative to gravity. These so-called
      gravitropic setpoint angles (GSAs) are intriguing because their maintenance
      requires that root and shoot lateral organs are able to effect tropic growth both
      with and against the gravity vector. This chapter describes methods and
      considerations relevant to the investigation of mechanisms underlying GSA
      control. 

PMID- 25981767
TI  - Imaging of dynamic ion signaling during root gravitropism.
AB  - Gravitropic signaling is a complex process that requires the coordinated action
      of multiple cell types and tissues. Ca(2+) and pH signaling are key components of
      gravitropic signaling cascades and can serve as useful markers to dissect the
      molecular machinery mediating plant gravitropism. To monitor dynamic ion
      signaling, imaging approaches combining fluorescent ion sensors and confocal
      fluorescence microscopy are employed, which allow the visualization of pH and
      Ca(2+) changes at the level of entire tissues, while also providing high
      spatiotemporal resolution. Here, I describe procedures to prepare Arabidopsis
      seedlings for live cell imaging and to convert a microscope for vertical stage
      fluorescence microscopy. With this imaging system, ion signaling can be monitored
      during all phases of the root gravitropic response. 

PMID- 25981768
TI  - Live cell imaging of cytoskeletal and organelle dynamics in gravity-sensing cells
      in plant gravitropism.
AB  - Plants sense gravity and change their morphology/growth direction accordingly
      (gravitropism). The early process of gravitropism, gravity sensing, is supposed
      to be triggered by sedimentation of starch-filled plastids (amyloplasts) in
      statocytes such as root columella cells and shoot endodermal cells. For several
      decades, many scientists have focused on characterizing the role of the
      amyloplasts and observed their intracellular sedimentation in various plants.
      Recently, it has been discovered that the complex sedimentary movements of the
      amyloplasts are created not only by gravity but also by cytoskeletal/organelle
      dynamics, such as those of actin filaments and the vacuolar membrane. Thus, to
      understand how plants sense gravity, we need to analyze both amyloplast movements
      and their regulatory systems in statocytes. We have developed a vertical-stage
      confocal microscope that allows multicolor fluorescence imaging of amyloplasts,
      actin filaments and vacuolar membranes in vertically oriented plant tissues. We
      also developed a centrifuge microscope that allows bright-field imaging of
      amyloplasts during centrifugation. These microscope systems provide new insights
      into gravity-sensing mechanisms in Arabidopsis. 

PMID- 25981758
TI  - Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del
      CFTR.
AB  - BACKGROUND: Cystic fibrosis is a life-limiting disease that is caused by
      defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR)
      protein activity. Phe508del is the most common CFTR mutation. METHODS: We
      conducted two phase 3, randomized, double-blind, placebo-controlled studies that
      were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in
      combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of
      age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR
      mutation. In both studies, patients were randomly assigned to receive either
      lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with
      ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary
      end point was the absolute change from baseline in the percentage of predicted
      forced expiratory volume in 1 second (FEV1) at week 24. RESULTS: A total of 1108
      patients underwent randomization and received study drug. The mean baseline FEV1
      was 61% of the predicted value. In both studies, there were significant
      improvements in the primary end point in both lumacaftor-ivacaftor dose groups;
      the difference between active treatment and placebo with respect to the mean
      absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0
      percentage points (P<0.001), which corresponded to a mean relative treatment
      difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of
      pulmonary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups
      than in the placebo group; the rate of events leading to hospitalization or the
      use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as
      well. The incidence of adverse events was generally similar in the lumacaftor
      ivacaftor and placebo groups. The rate of discontinuation due to an adverse event
      was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those
      who received placebo. CONCLUSIONS: These data show that lumacaftor in combination
      with ivacaftor provided a benefit for patients with cystic fibrosis homozygous
      for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others;
      TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.).

PMID- 25981769
TI  - Auxin carrier and signaling dynamics during gravitropic root growth.
AB  - Plant growth relates to gravity, ensuring that roots grow downwards into the soil
      and shoots expand aerially. The phytohormone auxin mediates tropistic growth
      responses, such as root gravitropism. Gravity perception in the very tip of the
      roots triggers carrier-dependent, asymmetric redistribution of auxin, leading to
      differential auxin responses and growth regulation at the upper and lower root
      flanks. This cellular, asymmetry-breaking event will eventually lead to root
      bending towards the gravity vector. Here, we show how to investigate auxin
      signaling and auxin carrier dynamics during root gravitropic response, using a
      chambered cover glass in combination with a confocal live cell imaging approach.
      To exemplify this method, we used established lines expressing transcriptional
      and translational green fluorescent protein (GFP) fusions to the auxin responsive
      promoter element DR5rev and the prominent auxin carrier PIN-FORMED2 (PIN2),
      respectively. Transgenic seedlings were placed and grown in the chambered cover
      glasses, enabling defined gravitropic stimulations prior to imaging. This method
      is optimal for inverted microscopes and significantly reduces stressful
      manipulations during specimen preparation. 

PMID- 25981770
TI  - Imaging and quantitative methods for studying cytoskeletal rearrangements during
      root development and gravitropism.
AB  - High-resolution imaging of cytoskeletal structures paves the way for standardized
      methods to quantify cytoskeletal organization. Here we provide a detailed
      description of the analysis performed to determine the microtubule patterns in
      gravistimulated roots, using the recently developed software tool MicroFilament
      Analyzer. 

PMID- 25981771
TI  - Methods for RNA profiling of gravi-responding plant tissues.
AB  - Plant transcriptional responses to gravity stimulation by reorientation are among
      the fastest measured in any tissue or species. Upon reorientation, changes in
      abundance of specific mRNAs can be measured within seconds or minutes, for
      plastid or nuclear encoded genes, respectively. Identifying fast gravity-induced
      transcripts has been made possible by the development of high-throughput
      technology for qualitative and quantitative RNA analysis. RNA profiling has
      undergone further rapid development due to its enormous potential in basic
      sciences and medical applications. We describe here the current and most widely
      used methods to profile the changes in an entire transcriptome by high-throughput
      sequencing of RNA fractions (RNAseq) and single gene transcript analysis using
      real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

PMID- 25981772
TI  - Proteomic approaches and their application to plant gravitropism.
AB  - Proteomics is a powerful technique that allows researchers a window into how an
      organism responds to a mutation, a specific environment, or at a distinct point
      during development by quantifying relative protein abundance and
      posttranslational modifications. Here, we describe methods for the proteomic
      analysis of Arabidopsis thaliana tissue. Extraction protocols are provided for
      isolation of soluble, plasma membrane, and tonoplast proteins. In addition, basic
      analysis and quality metrics for MS/MS data are discussed. The protocols outlined
      have the potential to unlock new avenues of research that are not possible
      through basic genetics or transcriptomic approaches. By combining proteomic
      information with known gene regulatory patterns, researchers can gain a complete
      picture of how molecular pathways, such as those required for gravitropism, are
      initiated, regulated, and terminated. 

PMID- 25981773
TI  - Assays for root hydrotropism and response to water stress.
AB  - Roots of most terrestrial plants show hydrotropic curvature when exposed to a
      moisture gradient. Though this root response is difficult to visualize in the
      soil habitat, there are reports of hydrotropism as an inherent response of
      primary roots of different plant species, such as Arabidopsis thaliana, Pisum
      sativum, and Zea mays L., from in vitro system studies. Many plant species use
      hydrotropism as a mechanism of avoidance to water stress. The actively growing
      root tip has the ability to change its direction towards greater water
      availability by differential growth in the elongation zone. The study of this
      tropic response has been challenged by the interaction of gravitropism,
      thigmotropism and possibly phototropism. It is hard to visualize hydrotropic
      curvature in vitro unless all other stimuli are neutralized by the presence of a
      moisture gradient. In this chapter, we describe methods for preparation of two
      assay systems used to visualize hydrotropic curvature in the primary roots of
      Arabidopsis and one moisture gradient system used for maize root seedlings. 

PMID- 25981774
TI  - Evaluating mechano-transduction and touch responses in plant roots.
AB  - Mechanical forces can be imposed on plants either from the environment, through
      factors such as the weather, mechanical properties of the soil and animal
      movement, or through the internal forces generated by the interplay between
      turgor-driven growth and the rigid plant cell wall. Such mechanical cues have
      profound effects on plant growth and development leading to responses ranging
      from directional growth patterns as seen, e.g., in tendrils coiling around
      supports, to the reprogramming of entire developmental programs. Thus, assays to
      assess mechanical sensitivity and response provide important tools for helping
      understand a wide range of plant physiological and developmental responses. Here,
      we describe simple assays to monitor mechanical response in the plant root system
      focusing on the quantification of root skewing, waving and obstacle avoidance. 

PMID- 25981775
TI  - Expressing and characterizing mechanosensitive channels in Xenopus oocytes.
AB  - The oocytes of the African clawed frog (Xenopus laevis) comprise one of the most
      widely used membrane protein expression systems. While frequently used for
      studies of transporters and ion channels, the application of this system to the
      study of mechanosensitive ion channels has been overlooked, perhaps due to a
      relative abundance of native expression systems. Recent advances, however, have
      illustrated the advantages of the oocyte system for studying plant and bacterial
      mechanosensitive channels. Here we describe in detail the methods used for
      heterologous expression and characterization of bacterial and plant
      mechanosensitive channels in Xenopus oocytes. 

PMID- 25981776
TI  - Flowering shoots of ornamental crops as a model to study cellular and molecular
      aspects of plant gravitropism.
AB  - Flowering shoots offer a very convenient and excellent model system for in-depth
      study of shoot gravitropism in regular stems rather than in special aboveground
      organs, showing how plants cope with the force of gravity on Earth and change in
      orientation. Regarding the emerging notion that roots and shoots execute their
      gravitropic bending by different mechanisms, the use of flowering shoots offers
      additional confirmation for the suggested shoot-sensing mechanisms initially
      found in Arabidopsis. As a part of confirming this mechanism, studying this
      unique model system also enabled elucidation of the sequence of events operating
      in gravity signalling in shoots. Hence, using the system of flowering shoots
      provided an additional dimension to our understanding of shoot gravitropism and
      its hormonal regulation, which has been less advanced than root gravitropism.
      This is particularly important since the term "shoots" includes various
      aboveground organs. Hence, unlike other aboveground organs such as pulvini, the
      asymmetric growth in response to change in shoot orientation is accompanied in
      cut ornamental spikes by a continuous growth process. This chapter provides an
      overview of the basic methods, specifically developed or adapted from other
      graviresponding systems, for determining the main components which play a key
      role in gravistimulation signalling in flowering shoots. 

PMID- 25981777
TI  - Studying molecular changes during gravity perception and response in a single
      cell.
AB  - Early studies revealed a highly predictable pattern of gravity-directed growth
      and development in Ceratopteris richardii spores. This makes the spores a
      valuable model system for the study of how a single cell senses and responds to
      the force of gravity. Gravity regulates both the direction and magnitude of a
      trans-cell calcium current in germinating spores, and the orientation of this
      current predicts the polarization of spore development. Molecular techniques have
      been developed to evaluate the transcriptomic and proteomic profiles of spores
      before and after gravity establishes the polarity of their development. Here we
      describe these techniques, along with protocols for sterilizing the spores,
      sowing them in a solid or liquid growth media, and evaluating germination. 

PMID- 25981778
TI  - Live cell and immuno-labeling techniques to study gravitational effects on single
      plant cells.
AB  - The constant force of gravity plays a primordial role in the ontogeny of all
      living organisms. Plants, for example, develop their roots and shoots in
      accordance with the direction of the gravitational vector. Any change in the
      magnitude and/or the direction of gravity has an important impact on the
      development of tissues and cells. In order to understand how the gravitational
      force affects plant cell growth and differentiation, we established two
      complementary experimental procedures with which the effect of hyper-gravity on
      single plant cell development can be assessed. The single model cell system we
      used is the pollen tube or male gametophyte which, because of its rapid growth
      behavior, is known for its instant response to external stresses. The
      physiological response of the pollen tube can be assessed in a quantitative
      manner based on changes in the composition and spatial distribution of its cell
      wall components and in the precisely defined pattern of its very dynamic
      cytoplasmic streaming. Here, we provide a detailed description of the steps
      required for the immuno-localization of various cell wall components using
      microwave-assisted techniques and we explain how live imaging of the
      intracellular traffic can be achieved under hyper-gravity conditions. 

PMID- 25981779
TI  - Use of high gradient magnetic fields to evaluate gravity perception and response
      mechanisms in plants and algae.
AB  - Magnetic gradients have the valuable property of exerting a repulsive
      ponderomotive force onto diamagnetic compounds. A carefully designed gradient and
      proper positioning of biological material can be used to manipulate gravisensing
      organelles such as amyloplasts of higher plants and other statoliths such as the
      BaSO4-filled vesicles of Characean algae. This chapter describes the main
      considerations of magnetic gradients and their application as a localized force
      field to manipulate (sort) cellular organelles based on their magnetic
      properties. Many of the inferences from such activities have yet to be
      investigated. 

PMID- 25981780
TI  - Use of microgravity simulators for plant biological studies.
AB  - Simulated microgravity and partial gravity research on Earth is highly convenient
      for every space biology researcher due to limitations of access to spaceflight.
      However, the use of ground-based facilities for microgravity simulation is far
      from simple. Microgravity simulation usually results in the need to consider
      additional environmental parameters which appear as secondary effects in the
      generation of altered gravity. These secondary effects may interfere with gravity
      alteration in the changes observed in the biological processes under study.
      Furthermore, ground-based facilities are also capable of generating hypergravity
      or fractional gravity conditions, which are worth being tested and compared with
      the results of microgravity exposure. Multiple technologies (2D clinorotation,
      random positioning machines, magnetic levitators or centrifuges), experimental
      hardware (proper use of containers and substrates for the seedlings or cell
      cultures), and experimental requirements (some life support/environmental
      parameters are more difficult to provide in certain facilities) should be
      collectively considered in defining the optimal experimental design that will
      allow us to anticipate, modify, or redefine the findings provided by the scarce
      spaceflight opportunities that have been (and will be) available. 

PMID- 25981781
TI  - Conducting plant experiments in space.
AB  - The growth and development of plants during spaceflight have important
      implications for both basic and applied research supported by NASA and other
      international space agencies. While there have been many reviews of plant space
      biology, the present chapter attempts to fill a gap in the literature on the
      actual process and methods of performing plant research in the spaceflight
      environment. The author has been a principal investigator on six spaceflight
      projects and has another two space experiments in development. These experiences
      include using the US Space Shuttle, the former Russian space station Mir, and the
      International Space Station, utilizing the Space Shuttle and Space X as launch
      vehicles. While there are several ways to obtain a spaceflight opportunity, this
      review focuses on using the NASA peer-reviewed sciences approach to get an
      experiment manifested for flight. Three narratives for the implementation of
      plant space biology experiments are considered from rapid turnaround of a few
      months to a project with new hardware development that lasted 6 years. The many
      challenges of spaceflight research include logistical and resource constraints
      such as crew time, power, cold stowage, and data downlinks, among others.
      Additional issues considered are working at NASA centers, hardware development,
      safety concerns, and the engineering versus science culture in space agencies.
      The difficulties of publishing the results from spaceflight research based on
      such factors as the lack of controls, limited sample size, and the indirect
      effects of the spaceflight environment also are summarized. Finally, lessons
      learned from these spaceflight experiences are discussed in the context of
      improvements for future space-based research projects with plants. 

PMID- 25981782
TI  - Spaceflight exploration in plant gravitational biology.
AB  - Before there was access to space, all experiments on plant tropisms were
      conducted upon the background of gravity. The gravity vector could be disrupted,
      such as with clinorotation and random positioning machines, and by manipulating
      incident angles of root growth with respect to gravity, such as with Darwin's
      plants on slanted plates, but gravity could not be removed from the experimental
      equation. Access to microgravity through spaceflight has opened new doors to
      plant research. Here we provide an overview of some of the methodologies of
      conducting plant research in the unique spaceflight environment. 

PMID- 25981783
TI  - Hypergravity experiments to evaluate gravity resistance mechanisms in plants.
AB  - Hypergravity generated by centrifugal acceleration is the only practical method
      to modify the magnitude of gravitational acceleration for a sufficient duration
      on Earth and has been used to analyze the nature and mechanism of graviresponse,
      particularly gravity resistance, in plants. Plant organs are generally resistant
      to gravitational acceleration. Hypergravity produced from centrifugation speeds
      in the range of 10-300 * g, which is easily produced by a benchtop centrifuge, is
      often used during plant experiments. After centrifugation, the plant material is
      fixed with suitable fixatives in appropriate sample storage containers such as
      the Chemical Fixation Bag. The material is then analyzed with a variety of
      methods, depending on the purpose of the experiment. Plant material fixed with
      the RNAlater((r)) solution can be sequentially used for determining the
      mechanical properties of the cell wall, for RNA extraction (which is necessary
      for gene expression analysis), for estimating the enzyme activity of the cell
      wall proteins, and for determining the levels as well as the compositions of cell
      wall polysaccharides. The plant material can also be used directly for
      microscopic observation of cellular components such as cortical microtubules.

PMID- 25981784
TI  - Consumer Acceptability of Cucumber Pickles Produced by Fermentation in Calcium
      Chloride Brine for Reduced Environmental Impact.
AB  - Fermentation of cucumbers in calcium chloride (CaCl2 ) brine has been proposed as
      an alternative process to reduce the environmental impact of traditional, high
      salt fermentations. The objective of this research was to determine whether
      consumer acceptability of pickle products would be impacted by fermentation and
      storage of cucumbers in CaCl2 brine. Cucumbers were fermented and stored with
      0.1M CaCl2 or 1M sodium chloride (NaCl) in open-air, 3000 gal tanks at a
      commercial facility and processed into hamburger dill chips containing 0.38M
      NaCl. Cucumbers fermented in CaCl2 required additional desalting to reduce CaCl2
      concentrations to that of current products. Consumers (n = 101) showed no
      significant preference for pickles from different fermentation treatments,
      whether stored for 2 mo (P = 0.75) or 8 mo (P = 0.68) prior to processing. In
      contrast, NaCl fermented pickles were preferred over CaCl2 fermented pickles
      stored for 10 mo and desalted only once (P < 0.01). A series of preference tests
      indicated that the taste of CaCl2 was not the factor affecting consumer
      preference, and the 50% detection threshold of CaCl2 in dill pickle chips was
      found to be 61.8 +/- 7.6 mM, indicating that processors could potentially use
      CaCl2 fermentations with a single desalting step. Consumer liking of flavor (n =
      73) was not influenced by fermentation in CaCl2 or by 23 or 35 mM CaCl2 in
      finished products (P > 0.05), but variability in texture decreased consumer
      liking (P < 0.05). Although promising, individual fermentation variability and
      texture quality of CaCl2 fermented products should be further evaluated prior to
      broad implementation of this process. 

PMID- 25981786
TI  - Underutilization of IV nitrates in the treatment of acute heart failure.
AB  - Acute heart failure (AHF) is a growing public health concern with high inhospital
      mortality and costs. Clinical practice guidelines, underpinned by positive
      randomized controlled trials, recommend the early use of intravenous (IV)
      nitrates in the treatment of AHF. However, the "real-world" usage of IV nitrates
      has not been clearly defined. The objective of this study was to examine the use
      of IV nitrates in the treatment of AHF as recommended by clinical practice
      guidelines. A case-record analysis was conducted of all admissions with AHF at a
      large teaching hospital. Of the 81 AHF patients (mean age 77 +/- 11, mean SBP 130
      +/- 27 mmHg) enrolled for this analysis, only 5 (6%) received IV nitrates at the
      time of AHF admission. Forty (49%, mean age 77 +/- 11, mean SBP 131 +/- 27 mmHg)
      of these 81 patients met the guideline criteria for suitability for IV nitrates
      and only 5 (12%) of these received them during this admission. Patients who
      received IV nitrates were more likely to have higher blood pressure and all had
      myocardial ischemia as a precipitant. Seventy-five (93%) of the total population
      received loop diuretics on admission. Overall, this study shows that loop
      diuretics remain the first-line therapy in AHF with little use of IV nitrates,
      despite recommendations from clinical practice guidelines. 

PMID- 25981785
TI  - Bi-component T2 * analysis of bound and pore bone water fractions fails at high
      field strengths.
AB  - Osteoporosis involves the degradation of the bone's trabecular architecture,
      cortical thinning and enlargement of cortical pores. Increased cortical porosity
      is a major cause of the decreased strength of osteoporotic bone. The majority of
      cortical pores, however, are below the resolution limit of MRI. Recent work has
      shown that porosity can be evaluated by MRI-based quantification of bone water.
      Bi-exponential T2 * fitting and adiabatic inversion preparation are the two most
      common methods purported to distinguish bound and pore water in order to quantify
      matrix density and porosity. To assess the viability of T2 * bi-component
      analysis as a method for the quantification of bound and pore water fractions, we
      applied this method to human cortical bone at 1.5, 3, 7 and 9.4 T, and validated
      the resulting pool fractions against micro-computed tomography-derived porosity
      and gravimetrically determined bone densities. We also investigated alternative
      methods: two-dimensional T1 -T2 * bi-component fitting by incorporation of
      saturation recovery, one- and two-dimensional fitting of Carr-Purcell-Meiboom
      Gill (CPMG) echo amplitudes, and deuterium inversion recovery. The short-T2 *
      pool fraction was moderately correlated with porosity (R(2)  = 0.70) and matrix
      density (R(2)  = 0.63) at 1.5 T, but the strengths of these associations were
      found to diminish rapidly as the field strength increased, falling below R(2)  =
      0.5 at 3 T. The addition of the T1 dimension to bi-component analysis only
      slightly improved the strengths of these correlations. T2 *-based bi-component
      analysis should therefore be used with caution. The performance of deuterium
      inversion recovery at 9.4 T was also poor (R(2)  = 0.50 vs porosity and R(2)  =
      0.46 vs matrix density). The CPMG-derived short-T2 fraction at 9.4 T, however,
      was highly correlated with porosity (R(2)  = 0.87) and matrix density (R(2)  =
      0.88), confirming the utility of this method for independent validation of bone
      water pools.

PMID- 25981787
TI  - A dopamine-modulated neural circuit regulating aversive taste memory in
      Drosophila.
AB  - Taste memories allow animals to modulate feeding behavior in accordance with past
      experience and avoid the consumption of potentially harmful food [1]. We have
      developed a single-fly taste memory assay to functionally interrogate the neural
      circuitry encoding taste memories [2]. Here, we screen a collection of Split-GAL4
      lines that label small populations of neurons associated with the fly memory
      center-the mushroom bodies (MBs) [3]. Genetic silencing of PPL1 dopamine neurons
      disrupts conditioned, but not naive, feeding behavior, suggesting these neurons
      are selectively involved in the conditioned taste response. We identify two PPL1
      subpopulations that innervate the MB alpha lobe and are essential for aversive
      taste memory. Thermogenetic activation of these dopamine neurons during training
      induces memory, indicating these neurons are sufficient for the reinforcing
      properties of bitter tastant to the MBs. Silencing of either the intrinsic MB
      neurons or the output neurons from the alpha lobe disrupts taste conditioning.
      Thermogenetic manipulation of these output neurons alters naive feeding response,
      suggesting that dopamine neurons modulate the threshold of response to appetitive
      tastants. Taken together, these findings detail a neural mechanism underlying the
      formation of taste memory and provide a functional model for dopamine-dependent
      plasticity in Drosophila. 

PMID- 25981789
TI  - Metagenome Sequencing of the Hadza Hunter-Gatherer Gut Microbiota.
AB  - Through human microbiome sequencing, we can better understand how host
      evolutionary and ontogenetic history is reflected in the microbial function.
      However, there has been no information on the gut metagenome configuration in
      hunter-gatherer populations, posing a gap in our knowledge of gut microbiota (GM)
      host mutualism arising from a lifestyle that describes over 90% of human
      evolutionary history. Here, we present the first metagenomic analysis of GM from
      Hadza hunter-gatherers of Tanzania, showing a unique enrichment in metabolic
      pathways that aligns with the dietary and environmental factors characteristic of
      their foraging lifestyle. We found that the Hadza GM is adapted for broad
      spectrum carbohydrate metabolism, reflecting the complex polysaccharides in their
      diet. Furthermore, the Hadza GM is equipped for branched-chain amino acid
      degradation and aromatic amino acid biosynthesis. Resistome functionality
      demonstrates the existence of antibiotic resistance genes in a population with
      little antibiotic exposure, indicating the ubiquitous presence of environmentally
      derived resistances. Our results demonstrate how the functional specificity of
      the GM correlates with certain environment and lifestyle factors and how
      complexity from the exogenous environment can be balanced by endogenous
      homeostasis. The Hadza gut metagenome structure allows us to appreciate the co
      adaptive functional role of the GM in complementing the human physiology,
      providing a better understanding of the versatility of human life and
      subsistence. 

PMID- 25981790
TI  - The many colours of 'the dress'.
AB  - There has been an intense discussion among the public about the colour of a
      dress, shown in a picture posted originally on Tumblr
      (http://swiked.tumblr.com/post/112073818575/guys-please-help-me-is-this-dress
      white-and; accessed on 10:56 am GMT on Tue 24 Mar 2015). Some people argue that
      they see a white dress with golden lace, while others describe the dress as blue
      with black lace. Here we show that the question "what colour is the dress?" has
      more than two answers. In fact, there is a continuum of colour percepts across
      different observers. We measured colour matches on a calibrated screen for two
      groups of observers who had reported different percepts of the dress.
      Surprisingly, differences between the two groups arose mainly from differences in
      lightness, rather than chromaticity of the colours they adjusted to match the
      dress. We speculate that the ambiguity arises in the case of this particular
      image because the distribution of colours within the dress closely matches the
      distribution of natural daylights. This makes it more difficult to disambiguate
      illumination changes from those in reflectance. 

PMID- 25981788
TI  - The Ran-GTP gradient spatially regulates XCTK2 in the spindle.
AB  - Ran is a small GTP binding protein that was originally identified as a regulator
      of nucleocytoplasmic transport [1] and subsequently found to be important for
      spindle formation [2-5]. In mitosis, a gradient of Ran-GTP emanates from
      chromatin and diminishes toward spindle poles [6]. Ran-GTP promotes spindle self
      organization through the release of importin-bound spindle assembly factors
      (SAFs), which stimulate microtubule (MT) nucleation and organization and regulate
      MT dynamics [7-9]. Although many SAFs are non-motile MT-associated proteins, such
      as NuMA, TPX2, and HURP [7, 10-12], Ran also controls motor proteins, including
      Kid and HSET/XCTK2 [13, 14]. The Kinesin-14 XCKT2 is important for spindle
      assembly and pole organization [15-20], and Ran-GTP is proposed to promote XCKT2
      MT crosslinking activity by releasing importin alpha/beta from a bipartite
      nuclear localization signal (NLS) located in the tail domain [14]. Here, we show
      that the Ran-GTP gradient spatially regulates XCTK2 within the spindle. A
      flattened Ran-GTP gradient blocked the ability of excess XCTK2 to stimulate
      bipolar spindle assembly and resulted in XCTK2-mediated bundling of free MTs.
      These effects required the XCTK2 tail, which promoted the motility of XCTK2
      within the spindle independent of the Ran-GTP gradient. In addition, the turnover
      kinetics of XCTK2 were spatially controlled: they were faster near the poles
      relative to the chromatin, but not with a mutant XCTK2 that cannot bind to
      importin alpha/beta. Our results support a model in which the Ran-GTP gradient
      spatially coordinates motor localization with motility to ensure efficient
      spindle formation. 

PMID- 25981792
TI  - Asymmetries in blue-yellow color perception and in the color of 'the dress'.
AB  - The perception of color poses daunting challenges, because the light spectrum
      reaching the eye depends on both the reflectance of objects and the spectrum of
      the illuminating light source. Solving this problem requires sophisticated
      inferences about the properties of lighting and surfaces, and many striking
      examples of 'color constancy' illustrate how our vision compensates for
      variations in illumination to estimate the color of objects (for example [1-3]).
      We discovered a novel property of color perception and constancy, involving how
      we experience shades of blue versus yellow. We found that surfaces are much more
      likely to be perceived as white or gray when their color is varied along bluish
      directions, compared with equivalent variations along yellowish (or reddish or
      greenish) directions. This selective bias may reflect a tendency to attribute
      bluish tints to the illuminant rather than the object, consistent with an
      inference that indirect lighting from the sky and in shadows tends to be bluish.
      The blue-yellow asymmetry has striking effects on the appearance of images when
      their colors are reversed, turning white to yellow and silver to gold, and helps
      account for the variation among observers in the colors experienced in 'the
      dress' image that recently consumed the internet. Observers variously describe
      the dress as blue-black or white-gold, and this has been explained by whether the
      dress appears to be in direct lighting or shade (for example [5]). We show that
      these individual differences and potential lighting interpretations also depend
      on the special ambiguity of blue, for simply reversing the image colors causes
      almost all observers to report the lighter stripes as yellowish.

PMID- 25981791
TI  - Behavioral responses to a repetitive visual threat stimulus express a persistent
      state of defensive arousal in Drosophila.
AB  - The neural circuit mechanisms underlying emotion states remain poorly understood.
      Drosophila offers powerful genetic approaches for dissecting neural circuit
      function, but whether flies exhibit emotion-like behaviors has not been clear. We
      recently proposed that model organisms may express internal states displaying
      "emotion primitives," which are general characteristics common to different
      emotions, rather than specific anthropomorphic emotions such as "fear" or
      "anxiety." These emotion primitives include scalability, persistence, valence,
      and generalization to multiple contexts. Here, we have applied this approach to
      determine whether flies' defensive responses to moving overhead translational
      stimuli ("shadows") are purely reflexive or may express underlying emotion
      states. We describe a new behavioral assay in which flies confined in an enclosed
      arena are repeatedly exposed to an overhead translational stimulus. Repetitive
      stimuli promoted graded (scalable) and persistent increases in locomotor velocity
      and hopping, and occasional freezing. The stimulus also dispersed feeding flies
      from a food resource, suggesting both negative valence and context
      generalization. Strikingly, there was a significant delay before the flies
      returned to the food following stimulus-induced dispersal, suggestive of a slowly
      decaying internal defensive state. The length of this delay was increased when
      more stimuli were delivered for initial dispersal. These responses can be
      mathematically modeled by assuming an internal state that behaves as a leaky
      integrator of stimulus exposure. Our results suggest that flies' responses to
      repetitive visual threat stimuli express an internal state exhibiting canonical
      emotion primitives, possibly analogous to fear in mammals. The mechanistic basis
      of this state can now be investigated in a genetically tractable insect species. 

PMID- 25981793
TI  - Polarized cell motility induces hydrogen peroxide to inhibit cofilin via cysteine
      oxidation.
AB  - Mesenchymal cell motility is driven by polarized actin polymerization [1].
      Signals at the leading edge recruit actin polymerization machinery to promote
      membrane protrusion, while matrix adhesion generates tractive force to propel
      forward movement. To work effectively, cell motility is regulated by a complex
      network of signaling events that affect protein activity and localization. H2O2
      has an important role as a diffusible second messenger [2], and mediates its
      effects through oxidation of cysteine thiols. One cell activity influenced by
      H2O2 is motility [3]. However, a lack of sensitive and H2O2-specific probes for
      measurements in live cells has not allowed for direct observation of H2O2
      accumulation in migrating cells or protrusions. In addition, the identities of
      proteins oxidized by H2O2 that contribute to actin dynamics and cell motility
      have not been characterized. We now show, as determined by fluorescence lifetime
      imaging microscopy, that motile cells generate H2O2 at membranes and cell
      protrusions and that H2O2 inhibits cofilin activity through oxidation of
      cysteines 139 (C139) and 147 (C147). Molecular modeling suggests that C139
      oxidation would sterically hinder actin association, while the increased negative
      charge of oxidized C147 would lead to electrostatic repulsion of the opposite
      negatively charged surface. Expression of oxidation-resistant cofilin impairs
      cell spreading, adhesion, and directional migration. These findings indicate that
      H2O2 production contributes to polarized cell motility through localized cofilin
      inhibition and that there are additional proteins oxidized during cell migration
      that might have similar roles. 

PMID- 25981794
TI  - Oxygen sensing coordinates photomorphogenesis to facilitate seedling survival.
AB  - Successful emergence from the soil is essential for plant establishment in
      natural and farmed systems. It has been assumed that the absence of light in the
      soil is the preeminent signal perceived during early seedling development,
      leading to a distinct morphogenic plan (skotomorphogenesis) [1], characterized by
      traits providing an adaptive advantage until emergence and photomorphogenesis.
      These traits include suppressed chlorophyll synthesis, promotion of hypocotyl
      elongation, and formation of a closed apical hook that protects the stem cell
      niche from damage [2, 3]. However, absence of light by itself is not a sufficient
      environmental signal for early seedling development [4, 5]. Reduced oxygen levels
      (hypoxia) can occur in water-logged soils [6-8]. We therefore hypothesized that
      below-ground hypoxia may be an important, but thus far undiscovered, ecological
      component regulating seedling development. Here, we show that survival and
      establishment of seedlings following darkness depend on their ability to sense
      hypoxia, through enhanced stability of group VII Ethylene Response Factor
      (ERFVII) transcription factors. Hypoxia is perceived as a positive environmental
      component in diverse taxa of flowering plants, promoting maintenance of
      skotomorphogenic traits. Hypoxia greatly enhances survival once light is
      perceived, while oxygen is necessary for the subsequent effective completion of
      photomorphogenesis. Together with light perception, oxygen sensing therefore
      allows an integrated response to the complex and changing physical
      microenvironment encountered during early seedling growth. We propose that plants
      monitor the soil's gaseous environment after germination, using hypoxia as a key
      external cue to protect the stem cell niche, thus ensuring successful rapid
      establishment upon emergence above ground. 

PMID- 25981795
TI  - Striking individual differences in color perception uncovered by 'the dress'
      photograph.
AB  - 'The dress' is a peculiar photograph: by themselves the dress' pixels are brown
      and blue, colors associated with natural illuminants, but popular accounts
      (#TheDress) suggest the dress appears either white/gold or blue/black. Could the
      purported categorical perception arise because the original social-media question
      was an alternative-forced-choice? In a free-response survey (N = 1401), we found
      that most people, including those naive to the image, reported white/gold or
      blue/black, but some said blue/brown. Reports of white/gold over blue/black were
      higher among older people and women. On re-test, some subjects reported a switch
      in perception, showing the image can be multistable. In a language-independent
      measure of perception, we asked subjects to identify the dress' colors from a
      complete color gamut. The results showed three peaks corresponding to the main
      descriptive categories, providing additional evidence that the brain resolves the
      image into one of three stable percepts. We hypothesize that these reflect
      different internal priors: some people favor a cool illuminant (blue sky),
      discount shorter wavelengths, and perceive white/gold; others favor a warm
      illuminant (incandescent light), discount longer wavelengths, and see blue/black.
      The remaining subjects may assume a neutral illuminant, and see blue/brown. We
      show that by introducing overt cues to the illumination, we can flip the dress
      color.

PMID- 25981797
TI  - Optimization of insulin pump therapy based on high order run-to-run control
      scheme.
AB  - BACKGROUND AND OBJECTIVES: Continuous subcutaneous insulin infusion (CSII) pump
      is widely considered a convenience and promising way for type 1 diabetes mellitus
      (T1DM) subjects, who need exogenous insulin infusion. In the standard insulin
      pump therapy, there are two modes for insulin infusion: basal and bolus insulin.
      The basal-bolus therapy should be individualized and optimized in order to keep
      one subject's blood glucose (BG) level within the normal range; however, the
      optimization procedure is troublesome and it perturb the patients a lot.
      Therefore, an automatic adjustment method is needed to reduce the burden of the
      patients, and run-to-run (R2R) control algorithm can be used to handle this
      significant task. METHODS: In this study, two kinds of high order R2R control
      methods are presented to adjust the basal and bolus insulin simultaneously. For
      clarity, a second order R2R control algorithm is first derived and studied.
      Furthermore, considering the differences between weekdays and weekends, a seventh
      order R2R control algorithm is also proposed and tested. RESULTS: In order to
      simulate real situation, the proposed method has been tested with uncertainties
      on measurement noise, drifts, meal size, meal time and snack. The proposed method
      can converge even when there are +/-60 min random variations in meal timing or +/
      50% random variations in meal size. CONCLUSIONS: According to the robustness
      analysis, one can see that the proposed high order R2R has excellent robustness
      and could be a promising candidate to optimize insulin pump therapy.

PMID- 25981796
TI  - Oncology patients overwhelmingly support tissue banking.
AB  - BACKGROUND: Translational biomedical research relies on the availability of human
      tissue to explore disease aetiology and prognostic factors, with the objective of
      developing better targeted treatments. The establishment of biobanks poses
      ongoing ethical considerations in relation to donors. This is a quantitative
      study exploring medical oncology patients' preferences for contributing to tissue
      biobanks. METHODS: The objectives of this study were to explore oncology
      patients' preferences about tissue banking, including: 1) willingness to donate;
      2) factors influencing donation decisions; 3) preferences about the use of
      donated tissue including permission systems, data linkage, and communication
      about research findings to donors. A cross-sectional survey was conducted in two
      tertiary oncology outpatient clinics. Eligible patients were approached by
      volunteers to complete a touchscreen survey in waiting rooms or while receiving
      intravenous therapy. Consenting participants completed demographic questions and
      received up to 12 previously validated items exploring preferences for donating
      tissue. RESULTS: 224 oncology outpatients participated over a ten month period
      (69.1 % consent rate; 64.4 % completion rate). Most participants were female (54
      %), were a mean age of 62 years, and diagnosed with breast (26 %) and bowel (20
      %) cancer. Most participants indicated willingness to donate tissue (84 %) and
      for their sample to be stored for future use (96 %). Participants preferred a
      blanket consent approach (71 %), samples to be linked to medical records (62 %)
      and for general results of the research (79 %) to be provided to them. Factors
      influencing willingness to donate tissue included personal (85 %) or familial
      health benefits (88 %) and a sense of duty to future patients (82 %).
      CONCLUSIONS: The overwhelming majority of oncology patients are willing to
      participate in a tissue bank, providing some support to explore 'opt-out' models
      of consent. To enhance patient acceptability, tissue banking programs should: (i)
      consider allowing blanket informed consent as well as opt-in models of consent;
      (ii) develop protocols allowing feedback of information about samples in line
      with patient preferences; (iii) provide clear information to potential donors
      about the benefits arising from donation.

PMID- 25981798
TI  - High broad-band photoresponsivity of mechanically formed InSe-graphene van der
      Waals heterostructures.
AB  - High broad-band photoresponsivity of mechanically formed InSe-graphene van der
      Waals heterostructures is achieved by exploiting the broad-band transparency of
      graphene, the direct bandgap of InSe, and the favorable band line up of InSe with
      graphene. The photoresponsivity exceeds that for other van der Waals
      heterostructures and the spectral response extends from the near-infrared to the
      visible spectrum. 

PMID- 25981799
TI  - Fluorescence analysis of NOM degradation by photocatalytic oxidation and its
      potential to mitigate membrane fouling in drinking water treatment.
AB  - This study examined the photocatalytic oxidation of natural organic matter (NOM)
      as a method to mitigate membrane fouling in drinking water treatment. ZnO and
      TiO2 photocatalysts were tested in concentrations ranging from 0.05 g L(-1) to
      0.5 g L(-1). Fluorescence peaks were used as the primary method to characterize
      the degradation of three specific NOM components - fulvic acid-like humic
      substances, humic acid-like humic substances, and protein-like substances during
      photocatalytic oxidation. Fluorescence peaks and Liquid Chromatography-Organic
      Carbon Detection (LC-OCD) analysis indicated that higher NOM degradation was
      obtained by photocatalytic oxidation with ZnO than with TiO2. Treatment of the
      feed water by ZnO photocatalytic oxidation was successful in reducing
      considerably the extent of hydraulically reversible and irreversible membrane
      fouling during ultrafiltration (UF) compared to feed water treatment with TiO2.
      Fouling during UF of water subjected to photocatalytic oxidation appeared to be
      caused by low molecular weight constituents of NOM generated during
      photocatalytic oxidation.

PMID- 25981800
TI  - Electrochemical oxidation of 2,4,5-trichlorophenoxyacetic acid by metal-oxide
      coated Ti electrodes.
AB  - Electrochemical oxidation of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) over
      metal-oxide-coated Ti anodes, i.e., Ti/SnO2-Sb/Ce-PbO2, Ti/SnO2-Sb and Ti/RuO2,
      was examined. The degradation efficiency of over 90% was attained at 20 min at
      different initial concentrations (0.5-20 mg L(-1)) and initial pH values (3.1
      11.2). The degradation efficiencies of 2,4,5-T on Ti/SnO2-Sb/Ce-PbO2, Ti/SnO2-Sb
      and Ti/RuO2 anodes were higher than 99.9%, 97.2% and 91.5% at 30 min,
      respectively, and the respective total organic carbon removal ratios were 65.7%,
      54.6% and 37.2%. The electrochemical degradation of 2,4,5-T in aqueous solution
      followed pseudo-first-order kinetics. The compounds, i.e., 2,5
      dichlorohydroquinone and 2,5-dihydroxy-p-benzoquinone, have been identified as
      the main aromatic intermediates by liquid chromatography-mass spectrometry. The
      results showed that the energy efficiencies of 2,4,5-T (20 mg L(-1)) degradation
      with Ti/SnO2-Sb/Ce-PbO2 anode at the optimal current densities from 2 to 16 mA
      cm(-2) ranged from 8.21 to 18.73 kWh m(-3).

PMID- 25981801
TI  - Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells
      exposed to heavy metals.
AB  - Heavy metals are common environmental toxicants with adverse effects on steroid
      biosynthesis. The importance of mitochondria has been recognized in cytotoxic
      mechanism of heavy metals on Leydig cells these years. But it is still poorly
      known. Our previous study reported that dihydrolipoamide dehydrogenase (DLD)
      located on the mitochondria was significantly decreased in Leydig cells exposed
      to cadmium, which suggested that DLD might be involved in the cytotoxic effects.
      Therefore, the altered expression of DLD was validated in rats and R2C cells
      exposed to cadmium, manganese and lead, and the role of DLD in the steroid
      synthesis pathway cAMP/PKA-ERK1/2 was investigated in this study. With a low
      expression of DLD, heavy metals dramatically reduced the levels of steroid
      hormone by inhibiting the activation of cAMP/PKA, PKC signaling pathway and the
      steroidogenic enzymes StAR, CYP11A1 and 3beta-HSD. After knockdown of DLD in R2C
      cells, progesterone synthesis was reduced by 40%, and the intracellular
      concentration of cAMP, protein expression of StAR, 3beta-HSD, PKA, and the
      phosphorylation of ERK1/2 were also decreased. These results highlight that DLD
      is down-regulation and related to steroid biosynthesis in Leyig cells exposed to
      heavy metals; cAMP/PKA act as downstream effector molecules of DLD, which
      activate phosphorylation of ERK1/2 to initiate the steroidogenesis. 

PMID- 25981802
TI  - Age-associated brain regions in gliomas: a volumetric analysis.
AB  - Both age of patients and tumor location are associated with tumor origin, genetic
      characteristics, and prognosis. The objective of this study was to investigate
      the relationship between tumor location and age at diagnosis in a large cohort of
      patients with a primary diagnosis of glioma. We consecutively enrolled a cohort
      of 200 adults with glioblastoma and another cohort of 200 adults with diffuse low
      grade gliomas. The magnetic resonance images of all tumors were manually
      segmented and then registered to a standard brain space. By using voxel-by-voxel
      regression analysis, specific brains regions associated with advanced age at
      tumor diagnosis were localized. In the low-grade gliomas cohort, the brain
      regions associated with advanced age at tumor diagnosis were mainly located in
      the right middle frontal region, while a region in the left temporal lobe,
      particularly at the subgranular zone, was associated with lower age at tumor
      diagnosis. In the glioblastoma cohort, the brain regions associated with advanced
      age at tumor diagnosis were mainly located in the temporal lobe, particularly at
      the posterior region of the subventricular zones. A region in the left inferior
      frontal region was associated with lower age at tumor diagnosis. Significant
      differences in the age of patients were found between tumors located in the
      identified regions and those located elsewhere in both cohorts. The current study
      demonstrated the correlation between tumor location and age at diagnosis, which
      implies differences in the origin of gliomas in young and older patients. 

PMID- 25981803
TI  - Radiosensitivity enhancement of radioresistant glioblastoma by epidermal growth
      factor receptor antibody-conjugated iron-oxide nanoparticles.
AB  - The epidermal growth factor receptor deletion variant EGFRvIII is known to be
      expressed in a subset of patients with glioblastoma (GBM) tumors that enhances
      tumorigenicity and also accounts for radiation and chemotherapy resistance.
      Targeting the EGFRvIII deletion mutant may lead to improved GBM therapy and
      better patient prognosis. Multifunctional magnetic nanoparticles serve as a
      potential clinical tool that can provide cancer cell targeted drug delivery,
      imaging, and therapy. Our previous studies have shown that an EGFRvIII-specific
      antibody and cetuximab (an EGFR- and EGFRvIII-specific antibody), when
      bioconjugated to IONPs (EGFRvIII-IONPs or cetuximab-IONPs respectively), can
      simultaneously provide sensitive cancer cell detection by magnetic resonance
      imaging (MRI) and targeted therapy of experimental GBM. In this study, we
      investigated whether cetuximab-IONPs can additionally allow for the
      radiosensitivity enhancement of GBM. Cetuximab-IONPs were used in combination
      with single (10 Gy * 1) or multiple fractions (10 Gy * 2) of ionizing radiation
      (IR) for radiosensitization of EGFRvIII-overexpressing human GBM cells in vitro
      and in vivo after convection-enhanced delivery (CED). A significant GBM antitumor
      effect was observed in vitro after treatment with cetuximab-IONPs and subsequent
      single or fractionated IR. A significant increase in overall survival of nude
      mice implanted with human GBM xenografts was found after treatment by cetuximab
      IONP CED and subsequent fractionated IR. Increased DNA double strands breaks
      (DSBs), as well as increased reactive oxygen species (ROS) formation, were felt
      to represent the mediators of the observed radiosensitization effect with the
      combination therapy of IR and cetuximab-IONPs treatment. 

PMID- 25981804
TI  - Donation after Circulatory Death Renal Allografts--Does Donor Age Greater than 50
      Years Affect Recipient Outcomes?
AB  - PURPOSE: Donation after circulatory death renal allografts are associated with
      excellent outcomes. We performed a retrospective chart review to investigate the
      impact of donor age on postoperative and intermediate term outcomes. MATERIALS
      AND METHODS: We compared recipient outcomes of donation after circulatory death
      allografts from donors older vs younger than 50 years. A total of 118 single
      donations after circulatory death renal transplants were performed at our
      institution between July 2006 and September 2013. Outcome variables (creatinine
      clearance, readmission rate, length of hospital stay, delayed graft function,
      graft loss and rejection) were compared between the 2 age categories using the
      Student t-test and the Pearson chi-square test. Independent prognosticators of
      creatinine clearance at 12 months were assessed with multivariate linear
      regression modeling. RESULTS: Mean +/- SD recipient age was 53.8 +/- 14.7 years
      and 45.8% of donation after circulatory death donors were older than 50 years.
      Median followup was 21 months (range 1 to 87). Recipients of kidney transplants
      from donation after circulatory death donors older than 50 years demonstrated
      lower creatinine clearance at 1 month (mean 50.3 +/- 25.3 vs 72.7 +/- 31.7 ml per
      minute, p <0.001), 3 months (62.5 +/- 22.9 vs 87.9 +/- 36.4, p <0.001) and 1 year
      (66.2 +/- 26.8 vs 87.8 +/- 38.7, p = 0.013). However, the 2 groups did not differ
      with regard to delayed graft function, graft loss, hospital readmissions or
      length of hospital stay. Multivariate linear regression demonstrated that donor
      age, recipient age, recipient gender and cold ischemia time were independent
      predictors of creatinine clearance at 12 months. CONCLUSIONS: Recipients of
      allografts from donors older than 50 years showed inferior renal function at 1
      year but the 2 groups had similar graft survival and short-term outcomes. Longer
      followup is required to determine long-term allograft survival.

PMID- 25981805
TI  - Understanding the Performance of Active Surveillance Selection Criteria in
      Diverse Urology Practices.
AB  - PURPOSE: We used data from MUSIC (Michigan Urological Surgery Improvement
      Collaborative) to evaluate the performance of published selection criteria for
      active surveillance in diverse urology practice settings. MATERIALS AND METHODS:
      For several active surveillance guidelines we calculated the proportion of men
      meeting each set of selection criteria who actually entered active surveillance,
      defined as the sensitivity of the guideline. After identifying the most sensitive
      guideline for the entire cohort we compared demographic and tumor characteristics
      between patients who met this guideline and entered active surveillance, and
      those who received initial definitive therapy. RESULTS: Of 4,882 men with newly
      diagnosed prostate cancer 18% underwent active surveillance. When applied to the
      entire cohort, the sensitivity of published guidelines ranged from 49% in Toronto
      to 62% at Johns Hopkins. At a practice level the sensitivity of Johns Hopkins
      criteria varied widely from 27% to 84% (p <0.001). Compared with men undergoing
      active surveillance, those meeting Johns Hopkins criteria who received definitive
      therapy were younger (p <0.001) and more likely to have a positive family history
      (p = 0.003), lower prostate specific antigen (p <0.001), a greater number of
      positive cores (2 vs 1) on biopsy (p <0.001) and a higher cancer volume in
      positive core(s) (p = 0.002). CONCLUSIONS: The sensitivity of published active
      surveillance selection criteria varies widely across diverse urology practices.
      Among patients meeting the most stringent criteria those who received initial
      definitive therapy had characteristics suggesting greater cancer risk,
      underscoring the nuanced clinical factors that influence treatment decisions.

PMID- 25981806
TI  - Antisynthetase syndrome: a review of etiopathogenesis, diagnosis and management.
AB  - Antisynthetase syndrome is a group of closely related rare diseases which
      clinically manifest with inflammatory myopathies, interstitial lung disease,
      inflammatory arthritis, skin hyperkeratosis (mechanic's hands) and Raynaud
      phenomenon. The pathophysiology of antisynthetase syndrome is not entirely
      understood, but genetic predisposition, viral infections and medication use may
      play a role. Certain antisynthetase antibodies are associated with various
      clinical presentations and a lower burden of inflammatory myopathies. Patients
      with antisynthetase syndrome have a worse prognosis than patients with pure
      inflammatory myopathies mainly because of interstitial lung disease. Future
      research should further investigate the pathogenesis of antisynthetase syndrome
      which could identify new therapeutic targets. It will be also important to study
      whether patients with AS are at increased risk of cancer and whether certain
      antisynthetase antibodies have any association with the risk of malignancy. 

PMID- 25981807
TI  - Understanding barriers to involving community midwives in identifying research
      participants; experience of the first steps randomised controlled trial.
AB  - OBJECTIVE: to explore barriers to the involvement of community midwives in
      identifying women in early pregnancy as potential participants in the first steps
      study, a randomised controlled trial of a new intervention to provide health and
      parenting support to potentially vulnerable women. DESIGN: descriptive
      qualitative investigation using semi-structured audio-recorded interviews.
      SETTING: community midwifery offices. PARTICIPANTS: volunteer sample of 13
      community midwives. MEASUREMENT: themes derived from content analysis. FINDINGS:
      understanding of their role in the research process was unclear to many midwives.
      Confusion arose about the difference between potential participant identification
      and trial recruitment. There were concerns about the eligibility criteria and it
      was suggested that there was insufficient time during booking appointments, and
      sometimes insufficient information, to determine potential eligibility. Midwives
      had concerns about some aspects of the intervention, which incorporated routine
      midwifery care, and had expectations that women may not like a group programme.
      This may have led some not to mention the trial. They were, however positive
      about the programme's potential for beneficial impacts on mothers and infants.
      KEY CONCLUSIONS: dedicated research midwives may be the best option if research
      studies need to identify potential participants early in pregnancy, so that they
      can communicate with all their colleagues. IMPLICATIONS FOR PRACTICE: if
      community midwives are asked to be involved in time-critical research they are
      likely to need additional local resources and support.

PMID- 25981808
TI  - Weight gain in healthy pregnant women in relation to pre-pregnancy BMI, diet and
      physical activity.
AB  - OBJECTIVE: to explore gestational weight gain in healthy women in relation to pre
      pregnancy Body Mass Index, diet and physical activity. DESIGN: a cross-sectional
      survey was conducted among 455 healthy pregnant women of all gestational ages
      receiving antenatal care from an independent midwife in the Netherlands. Weight
      gain was assessed using the Institute of Medicine (IOM) guidelines and classified
      as below, within, or above the guidelines. A multinomial regression analysis was
      performed with weight gain classifications as the dependent variable (within IOM
      guidelines as reference). Independent variables were pre-pregnancy Body Mass
      Index, diet (broken down into consumption of vegetables, fruit and fish) and
      physical activity (motivation to engage in physical activity, pre-pregnancy
      physical activity and decline in physical activity during pregnancy). Covariates
      were age, gestational age, parity, ethnicity, family income, education, perceived
      sleep deprivation, satisfaction with pre-pregnancy weight, estimated prepregnancy
      body mass index, smoking, having a weight gain goal and having received weight
      gain advice from the midwife. FINDINGS: forty-two per cent of the women surveyed
      gained weight within the guidelines. Fourteen per cent of the women gained weight
      below the guidelines and 44 per cent gained weight above the guidelines. Weight
      gain within the guidelines, compared to both above and below the guidelines, was
      not associated with pre-pregnancy Body Mass Index nor with diet. A decline in
      physical activity was associated with weight gain above the guidelines (OR 0.54,
      95 per cent CI 0.33-0.89). Weight gain below the guidelines was seen more often
      in women who perceived a greater sleep deprivation (OR 1.20, 95 per cent CI 1.02
      1.41). Weight gain above the guidelines was seen less often in Caucasian women in
      comparison to non-Caucasian women (OR 0.22, 95 per cent CI 0.08-0.56) and with
      women who did not stop smoking during pregnancy (OR 0.49, 95 per cent CI 0.25
      0.95). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: a decline in physical
      activity was the only modifiable factor in our population associated with weight
      gain above the gain recommended by the guidelines. Prevention of reduced physical
      activity during pregnancy seems a promising approach to promoting healthy weight
      gain. Interventions to promote healthy weight gain should focus on all women,
      regardless of pre-pregnancy body mass index.

PMID- 25981809
TI  - Actions of cAMP on calcium sensitization in human detrusor smooth muscle
      contraction.
AB  - OBJECTIVES: To clarify the effect of cAMP on the Ca(2+) -sensitized smooth muscle
      contraction in human detrusor, as well as the role of novel exchange protein
      directly activated by cAMP (Epac) in cAMP-mediated relaxation. MATERIALS AND
      METHODS: All experimental protocols to record isometric tension force were
      performed using alpha-toxin-permeabilized human detrusor smooth muscle strips.
      The mechanisms of cAMP-mediated suppression of Ca(2+) sensitization activated by
      10 MUm carbachol (CCh) and 100 MUm GTP were studied using a selective rho kinase
      (ROK) inhibitor, Y-27632, and a selective protein kinase C (PKC) inhibitor, GF
      109203X. The relaxation mechanisms were further probed using a selective protein
      kinase A (PKA) activator, 6-Bnz-cAMP and a selective Epac activator, 8-pCPT-2'-O
      Me-cAMP. RESULTS: We observed that CCh-induced Ca(2+) sensitization was inhibited
      by cAMP in a concentration-dependent manner. GF-109203X (10 MUm) but not Y-27632
      (10 MUm) significantly enhanced the relaxation effect induced by cAMP (100 MUm).
      6-Bnz-cAMP (100 MUm) predominantly decreased the tension force in comparison with
      8-pCPT-2'-O-Me-cAMP (100 MUm). CONCLUSIONS: We showed that cAMP predominantly
      inhibited the ROK pathway but not the PKC pathway. The PKA-dependent pathway is
      dominant, while Epac plays a minor role in human detrusor smooth muscle Ca(2+)
      sensitization.

PMID- 25981810
TI  - Treatment with two different doses of sonidegib in patients with locally advanced
      or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double
      blind phase 2 trial.
AB  - BACKGROUND: Patients with advanced basal cell carcinoma have limited treatment
      options. Hedgehog pathway signalling is aberrantly activated in around 95% of
      tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling
      inhibitor, in patients with advanced basal cell carcinoma. METHODS: BOLT is an
      ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients
      had locally advanced basal cell carcinoma not amenable to curative surgery or
      radiation or metastatic basal cell carcinoma. Patients were randomised via an
      automated system in a 1:2 ratio to receive 200 mg or 800 mg oral sonidegib daily,
      stratified by disease, histological subtype, and geographical region. The primary
      endpoint was the proportion of patients who achieved an objective response,
      assessed in the primary efficacy analysis population (patients with fully
      assessable locally advanced disease and all those with metastatic disease) with
      data collected up to 6 months after randomisation of the last patient. This trial
      is registered with ClinicalTrials.gov, number NCT01327053. FINDINGS: Between July
      20, 2011, and Jan 10, 2013, we enrolled 230 patients, 79 in the 200 mg sonidegib
      group, and 151 in the 800 mg sonidegib group. Median follow-up was 13.9 months
      (IQR 10.1-17.3). In the primary efficacy analysis population, 20 (36%, 95% CI 24
      50) of 55 patients receiving 200 mg sonidegib and 39 (34%, 25-43) of 116
      receiving 800 mg sonidegib achieved an objective response. In the 200 mg
      sonidegib group, 18 (43%, 95% CI 28-59) patients who achieved an objective
      response, as assessed by central review, were noted among the 42 with locally
      advanced basal cell carcinoma and two (15%, 2-45) among the 13 with metastatic
      disease. In the 800 mg group, 35 (38%, 95% CI 28-48) of 93 patients with locally
      advanced disease had an objective response, as assessed by central review, as did
      four (17%, 5-39) of 23 with metastatic disease. Fewer adverse events leading to
      dose interruptions or reductions (25 [32%] of 79 patients vs 90 [60%] of 150) or
      treatment discontinuation (17 [22%] vs 54 [36%]) occurred in patients in the 200
      mg group than in the 800 mg group. The most common grade 3-4 adverse events were
      raised creatine kinase (five [6%] in the 200 mg group vs 19 [13%] in the 800 mg
      group) and lipase concentration (four [5%] vs eight [5%]). Serious adverse events
      occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150
      patients in the 800 mg group. INTERPRETATION: The benefit-to-risk profile of 200
      mg sonidegib might offer a new treatment option for patients with advanced basal
      cell carcinoma, a population that is difficult to treat. FUNDING: Novartis
      Pharmaceuticals Corporation.

PMID- 25981811
TI  - The role of regorafenib in metastatic colorectal cancer.

PMID- 25981812
TI  - Stereotactic ablative radiotherapy versus lobectomy for operable stage I non
      small-cell lung cancer: a pooled analysis of two randomised trials.
AB  - BACKGROUND: The standard of care for operable, stage I, non-small-cell lung
      cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling.
      Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown
      promising results, but two independent, randomised, phase 3 trials of SABR in
      patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow
      accrual. We aimed to assess overall survival for SABR versus surgery by pooling
      data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies
      were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were
      randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node
      dissection or sampling. We did a pooled analysis in the intention-to-treat
      population using overall survival as the primary endpoint. Both trials are
      registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986).
      FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to
      surgery). Median follow-up was 40.2 months (IQR 23.0-47.3) for the SABR group and
      35.4 months (18.9-40.7) for the surgery group. Six patients in the surgery group
      died compared with one patient in the SABR group. Estimated overall survival at 3
      years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the
      surgery group (hazard ratio [HR] 0.14 [95% CI 0.017-1.190], log-rank p=0.037).
      Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and
      80% (65-97) in the surgery group (HR 0.69 [95% CI 0.21-2.29], log-rank p=0.54).
      In the surgery group, one patient had regional nodal recurrence and two had
      distant metastases; in the SABR group, one patient had local recurrence, four had
      regional nodal recurrence, and one had distant metastases. Three (10%) patients
      in the SABR group had grade 3 treatment-related adverse events (three [10%] chest
      wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No
      patients given SABR had grade 4 events or treatment-related death. In the surgery
      group, one (4%) patient died of surgical complications and 12 (44%) patients had
      grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than
      one patient in the surgery group were dyspnoea (four [15%] patients), chest pain
      (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could
      be an option for treating operable stage I NSCLC. Because of the small patient
      sample size and short follow-up, additional randomised studies comparing SABR
      with surgery in operable patients are warranted. FUNDING: Accuray Inc,
      Netherlands Organisation for Health Research and Development, NCI Cancer Center
      Support, NCI Clinical and Translational Science Award.

PMID- 25981813
TI  - Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned
      interim analysis of an international, open-label trial.
AB  - BACKGROUND: The Hedgehog pathway inhibitor vismodegib has shown clinical benefit
      in patients with advanced basal cell carcinoma and is approved for treatment of
      patients with advanced basal cell carcinoma for whom surgery is inappropriate.
      STEVIE was designed to assess the safety of vismodegib in a situation similar to
      routine practice, with a long follow-up. METHODS: In this multicentre, open-label
      trial, adult patients with histologically confirmed locally advanced basal cell
      carcinoma or metastatic basal cell carcinoma were recruited from regional
      referral centres or specialist clinics. Eligible patients were aged 18 years or
      older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0
      2, and adequate organ function. Patients with locally advanced basal cell
      carcinoma had to have been deemed ineligible for surgery. All patients received
      150 mg oral vismodegib capsules once a day on a continuous basis in 28-day
      cycles. The primary objective was safety (incidence of adverse events until
      disease progression or unacceptable toxic effects), with assessments on day 1 of
      each treatment cycle (28 days) by principal investigator and coinvestigators at
      the site. Efficacy variables were assessed as secondary endpoints. The safety
      evaluable population included all patients who received at least one dose of
      study drug. Patients with histologically confirmed basal cell carcinoma who
      received at least one dose of study drug were included in the efficacy analysis.
      An interim analysis was pre-planned after 500 patients achieved 1 year of follow
      up. This trial is registered with ClinicalTrials.gov, number NCT01367665. The
      study is still ongoing. FINDINGS: Between June 30, 2011, and Nov 6, 2014, we
      enrolled 1227 patients. At clinical cutoff (Nov 6, 2013), 499 patients (468 with
      locally advanced basal cell carcinoma and 31 with metastatic basal cell
      carcinoma) had received study drug and had the potential to be followed up for 12
      months or longer. Treatment was discontinued in 400 (80%) patients; 180 (36%) had
      adverse events, 70 (14%) had progressive disease, and 51 (10%) requested to stop
      treatment. Median duration of vismodegib exposure was 36.4 weeks (IQR 17.7-62.0).
      Adverse events happened in 491 (98%) patients; the most common were muscle spasms
      (317 [64%]), alopecia (307 [62%]), dysgeusia (269 [54%]), weight loss (162
      [33%]), asthenia (141 [28%]), decreased appetite (126 [25%]), ageusia (112
      [22%]), diarrhoea (83 [17%]), nausea (80 [16%]), and fatigue (80 [16%]). Most
      adverse events were grade 1 or 2. We recorded serious adverse events in 108 (22%)
      of 499 patients. Of the 31 patients who died, 21 were the result of adverse
      events. As assessed by investigators, 302 (66.7%, 62.1-71.0) of 453 patients with
      locally advanced basal cell carcinoma had an overall response (153 complete
      responses and 149 partial responses); 11 (37.9%; 20.7-57.7) of 29 patients with
      metastatic basal cell carcinoma had an overall response (two complete responses,
      nine partial responses). INTERPRETATION: This study assessed the use of
      vismodegib in a setting representative of routine clinical practice for patients
      with advanced basal cell carcinoma. Our results show that treatment with
      vismodegib adds a novel therapeutic modality from which patients with advanced
      basal cell carcinoma can benefit substantially. FUNDING: F Hoffmann-La Roche.

PMID- 25981815
TI  - Second-line dovitinib in metastatic endometrial cancer.

PMID- 25981814
TI  - Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non
      mutated advanced or metastatic endometrial cancer: a non-randomised, open-label,
      two-group, two-stage, phase 2 study.
AB  - BACKGROUND: Activating FGFR2 mutations are found in 10-16% of primary endometrial
      cancers and provide an opportunity for targeted therapy. We assessed the safety
      and activity of dovitinib, a potent tyrosine-kinase inhibitor of fibroblast
      growth factor receptors, VEGF receptors, PDGFR-beta, and c-KIT, as second-line
      therapy both in patients with FGFR2-mutated (FGFR2(mut)) endometrial cancer and
      in those with FGFR2-non-mutated (FGFR2(non-mut)) endometrial cancer. METHODS: In
      this phase 2, non-randomised, two-group, two-stage study, we enrolled adult women
      who had progressive disease after first-line chemotherapy for advanced or
      metastatic endometrial cancer from 46 clinical sites in seven countries. We
      grouped women according to FGFR2 mutation status and gave all women dovitinib
      (500 mg per day, orally, on a 5-days-on and 2-days-off schedule) until disease
      progression, unacceptable toxicity, death, or study discontinuation for any other
      reason. The primary endpoint was proportion of patients in each group who were
      progression-free at 18 weeks. For each group, the second stage of the trial
      (enrolment of 20 additional patients) could proceed if at least eight of the
      first 20 treated patients were progression free at 18 weeks. Activity was
      assessed in all enrolled patients and safety was assessed in all patients who
      received at least one dose of dovitinib. The completed study is registered with
      ClinicalTrials.gov, number NCT01379534. FINDINGS: Of 248 patients with FGFR2
      prescreening results, 27 (11%) had FGFR2(mut) endometrial cancer. Between Feb 17,
      2012, and Dec 13, 2013, we enrolled 22 patients in the FGFR2(mut) group and 31
      patients in the FGFR2(non-mut) group. Seven (31.8%, 95% CI 13.9-54.9) patients in
      the FGFR2(mut) group and nine (29.0%, 14.2-48.0) in the FGFR2(non-mut) group were
      progression-free at 18 weeks. On the basis of predefined criteria, neither group
      continued to stage two: seven (35%) of the first 20 patients in the FGFR2(mut)
      group were progression free at 18 weeks, as were five (25%) of the first 20 in
      the FGFR2(mut) population. Rates of treatment-emergent adverse events were
      similar between groups and events were most frequently gastrointestinal. Overall,
      the most common grade 3 or 4 adverse events suspected to be related to the study
      drug were hypertension (nine patients; 17%) and diarrhoea (five; 9%). The most
      frequently reported serious adverse events suspected to be related to study drug
      were pulmonary embolism (four patients; 8%), vomiting (four; 8%), dehydration
      (three; 6%), and diarrhoea (three; 6%). Only one death was deemed to be treatment
      related: one patient in the FGFR2(non-mut) group died from cardiac arrest with
      contributing reason of pulmonary embolism (grade 4, suspected to be study drug
      related) 4 days previously. INTERPRETATION: Second-line dovitinib in FGFR2(mut)
      and FGFR2(non-mut) advanced or metastatic endometrial cancer had single-agent
      activity, although it did not reach the prespecified study criteria. Observed
      treatment effects seemed independent of FGFR2 mutation status. These data should
      be considered exploratory and additional studies are needed. FUNDING: Novartis
      Pharmaceuticals.

PMID- 25981816
TI  - Systemic therapy for advanced basal cell carcinoma.

PMID- 25981817
TI  - SABR in early operable lung cancer: time for evidence.

PMID- 25981818
TI  - Regorafenib plus best supportive care versus placebo plus best supportive care in
      Asian patients with previously treated metastatic colorectal cancer (CONCUR): a
      randomised, double-blind, placebo-controlled, phase 3 trial.
AB  - BACKGROUND: In the international randomised phase 3 CORRECT trial (NCT01103323),
      regorafenib significantly improved overall survival versus placebo in patients
      with treatment-refractory metastatic colorectal cancer. Of the 760 patients in
      CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess
      regorafenib in a broader population of Asian patients with refractory metastatic
      colorectal cancer than was studied in CORRECT. METHODS: In this randomised,
      double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25
      hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we
      recruited Asian patients aged 18 years or older with progressive metastatic
      colorectal cancer who had received at least two previous treatment lines or were
      unable to tolerate standard treatments. Patients had to have an Eastern
      Cooperative Oncology Group performance status of 0 or 1, life expectancy of at
      least 3 months, and adequate bone marrow, liver, and renal function, without
      other uncontrolled medical disorders. We randomly allocated patients (2:1; with a
      computer-generated unicentric randomisation list [prepared by the study funder]
      and interactive voice response system; block size of six; stratified by
      metastatic site [single vs multiple organs] and time from diagnosis of metastatic
      disease [<18 months vs >=18 months]) to receive oral regorafenib 160 mg once
      daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were
      also to receive best supportive care. Participants, investigators, and the study
      funder were masked to treatment assignment. The primary endpoint was overall
      survival, and we analysed data on an intention-to-treat basis. This trial is
      registered with ClinicalTrials.gov, number NCT01584830. FINDINGS: Between April
      29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204
      patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a
      median follow-up of 7.4 months (IQR 4.3-12.2), overall survival was significantly
      better with regorafenib than it was with placebo (hazard ratio 0.55, 95% CI 0.40
      0.77, one-sided p=0.00016; median overall survival 8.8 months [95% CI 7.3-9.8] in
      the regorafenib group vs 6.3 months [4.8-7.6] in the placebo group). Drug-related
      adverse events occurred in 132 (97%) of 136 regorafenib recipients and 31 (46%)
      of 68 placebo recipients. The most frequent grade 3 or higher regorafenib-related
      adverse events were hand-foot skin reaction (22 [16%] of 136 patients in the
      regorafenib group vs none in the placebo group), hypertension (15 [11%] vs two
      [3%] of 68 patients in the placebo group), hyperbilirubinaemia (nine [7%] vs one
      [1%]), hypophosphataemia (nine [7%] vs none), alanine aminotransferase
      concentration increases (nine [7%] vs none), aspartate aminotransferase
      concentration increases (eight [6%] vs none), lipase concentration increases (six
      [4%] vs one [1%]), and maculopapular rash (six [4%] vs none). Drug-related
      serious adverse events occurred in 12 (9%) patients in the regorafenib group and
      three (4%) in the placebo group. INTERPRETATION: This phase 3 trial is the second
      to show an overall survival benefit with regorafenib compared with placebo in
      patients with treatment-refractory metastatic colorectal cancer, substantiating
      the role of regorafenib as an important treatment option for patients whose
      disease has progressed after standard treatments. In this trial, preceding
      standard treatments did not necessarily include targeted treatments. Adverse
      events were generally consistent with the known safety profile of regorafenib in
      this setting. FUNDING: Bayer HealthCare Pharmaceuticals.

PMID- 25981819
TI  - Tail wags the dog: activity of krait natriuretic peptide is determined by its C
      terminal tail in a natriuretic peptide receptor-independent manner.
AB  - Natriuretic peptides (NPs) are potent vasoactive hormones, which maintain
      pressure-volume homoeostasis. Snake venom NPs exhibit distinct biological
      activity compared with mammalian NPs due to subtle changes in their sequences. We
      recently identified a new NP from krait venom (KNP), with an unusual 38-residue
      long C-terminal tail, which has a propensity to form an alpha-helix. KNP mediates
      vasodilation via NP receptor (NPR) independent mechanisms on pre-contracted
      aortic strips in contrast with classical NPs. The infusion of KNP in
      anaesthetized rats resulted in a prolonged and sustained drop in blood pressure
      (BP) and heart rate (HR) with no renal effects in contrast with mammalian
      counterparts. Deletion mutant studies have revealed the presence of two
      functional segments in KNP, namely Ring and Helix. Although the Ring interacts
      with NPR, its contribution to the activity of KNP is shown to be negligible as
      both KNP and Helix elicit equipotent endothelium-dependent vasorelaxation.
      Further, KNP and Helix signalled through endothelial nitric oxide (NO) to mediate
      NPR-independent vasodilation. Thus, KNP exhibits non-canonical characteristics
      through its C-terminal tail, despite a functional NP ring. The present study has
      altered the paradigm of NP biology through the understanding of structure
      function relationships and may serve as a lead for the design of novel
      hypotensive agents. 

PMID- 25981820
TI  - Isoprenylated flavonoids from the root bark of Morus alba and their
      hepatoprotective and neuroprotective activities.
AB  - A new isoprenylated flavonoid, 2S-5,7,2',4'-tetrahydroxy-3',5'-di-(gamma,gamma
      dimethylallyl)flavanone, sanggenol Q (1), along with seven known isoprenylated
      flavonoids, sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5),
      sanggenon F (6), sanggenol O (7), and sanggenon N (8), three known Diels-Alder
      type adducts, sanggenon G (9), mulberrofuran G (10), and mulberrofuran C (11),
      and a known benzofuran, moracin E (12), were isolated from the root bark of Morus
      alba using silica gel, ODS, and Sephadex LH-20 column chromatography. Chemical
      structures were determined based on spectroscopic data analyses including NMR,
      MS, CD, and IR. For the first time, compounds 1 and 7 were isolated from the root
      bark of M. alba. All compounds were evaluated for hepatoprotective activity on t
      BHP-induced oxidative stress in HepG2 cells and neuroprotective activity on
      glutamate-induced cell death in HT22 cells. Compounds 1, 4, 8, 10, and 11 showed
      protective effects on t-BHP-induced oxidative stress with EC50 values of 6.94 +/-
      0.38, 30.32 +/- 6.82, 23.45 +/- 4.72, 15.31 +/- 2.21, and 0.41 +/- 0.48 MUM,
      respectively, and compounds 1, 2, 10, 11, and 12 showed protective effects on
      glutamate-induced cell death with EC50 values of 5.54 +/- 0.86, 34.03 +/- 7.71,
      19.71 +/- 0.71, 16.50 +/- 7.82, and 1.02 +/- 0.13 MUM, respectively. 

PMID- 25981821
TI  - Immune modulation of glycosaminoglycan derived from P. lewisi in TNF-alpha
      stimulated cells.
AB  - Poecilocoris lewisi (Korean name: "Kwangdaenolinjae") is a red-striped gold stink
      bug (insect) which has been used as a crude drug in traditional medicine of East
      Asia and Korea. In this study, ethanol extract and glycosaminoglycan from P.
      lewisi (Pl GAG), as an active substance among its components, were investigated
      for their potential anti-inflammatory actions. They were found to be a potent
      inducer of nitric oxide (NO) production from calf pulmonary artery endothelial
      (CPAE) cells and a stimulator of endothelial nitric oxide synthase in a dose
      dependent manner. The anti-inflammatory activities were also evaluated by
      determining the level of adhesion molecules related to atherogenesis and pro
      inflammatory cytokines, such as vascular cell adhesion molecule-1 (VCAM-1),
      intercellular adhesion molecule-1 (ICAM-1), secretory phospholipase A2, and
      prostaglandin E2, stimulated by tumor necrosis factor (TNF)-alpha in human
      umbilical vein endothelial cells (HUVEC). They also showed inhibitory effects on
      vascular endothelial growth factor (VEGF) production in HUVECs. Matrix
      metalloproteinases (MMP-2 and 9) were also inhibited by treatment with this
      extract or glycosaminoglycan. Furthermore, this GAG showed cytotoxicity against
      CT-26 colon cancer cells whereas having no cytotoxicity in CHO normal cells.
      Monosaccharide (amino, acidic, neutral monosaccharides) composition of used GAG
      was characterized by trimethylsilylated GC-MS analysis method. 

PMID- 25981822
TI  - Stimulated emission in cryogenic samples doped with free-base tetraazaporphine.
AB  - Thin cryogenic samples of inert gas solids doped with free-base tetraazaporphine
      (H2TAP) were irradiated with a tunable pulsed laser. Under resonant electronic
      excitation of the guest, specific vibronic transitions of the fluorescence
      spectra were found to be strongly enhanced with only a moderate increase of the
      laser power. This enhancement is due to stimulated emission (SE). The
      characteristics of SE bands are described in the three hosts (Ar, N2, and Ne)
      explored, as well as their excitation spectra. SE is observed in transitions
      involving different vibrational modes of the guest, depending on the host and the
      electronic excitation. The results are discussed in comparison with previous
      works on other tetrapyrrolic molecules trapped in inert gas matrices. From this
      comparison the key features required to observe SE are deduced to be: (1) SE can
      be obtained with various tetrapyrrolic molecules; (2) free-base molecules are
      preferable to their metallo-counterparts; (3) the results highlight a specific
      molecular vibrational mode involved in the process; and (4) cryogenic crystal
      structures are also of importance in the detection of SE. 

PMID- 25981823
TI  - Oligomerization of neutral peptides derived from the JC virus agnoprotein through
      a cysteine residue.
AB  - The JC virus is the causative agent of progressive multifocal
      leukoencephalopathy. The viral genome encodes a multifunctional protein known as
      agnoprotein which is essential for viral proliferation and reported to possess
      the oligomerization sequence. However, the structural relationship with the
      oligomerization is unclear. We synthesized 23 amino acid residue neutral peptides
      derived from the JC virus agnoprotein, Lys22 to Asp44. The secondary structures
      of these peptides were beta-sheet in aqueous buffer that converted to a helical
      structure in a hydrophobic environment. These peptides interestingly formed
      dimers and oligomers under oxidizing conditions. The oligomerization was
      facilitated by addition of bismaleimides and the derivative without thiol group
      did not form such oligomers. These results suggest that Agno(22-44) could be
      transmembrane and one disulfide bond between Cys40 triggers the oligomerization. 

PMID- 25981825
TI  - Current practice in and considerations for personalized medicine in lung cancer:
      From the patient's molecular biology to patient values and preferences.
AB  - Both at the individual and health system levels, the burden of complex illnesses
      associated with and which rise in mid- to later life, such as cancer, is expected
      to increase further. The advent of personalized medicine, or the use of a
      patient's genetic profile to guide medical decisions, is touted to substantially
      improve drug tolerance and efficacy and, in so doing, also improve the
      effectiveness and efficiency of oncological care. Amidst the hype and hope
      surrounding personalized cancer care, there is increasing concern about its
      unnecessary, unintended effects especially with regards to the financial burden
      of targeted therapies using specialty drugs. In this paper, we take a patient
      centered perspective on the therapeutic benefits of personalized medicine as well
      as the limitations of current practice and its psychological and financial
      toxicities by focusing on advanced-stage lung cancer. We argue that the modest
      clinical benefits of targeted therapy, premium prices for many specialty drugs
      and the narrow focus on the genetic constitution of individual patients run the
      risk of undercutting personalized lung cancer care's contribution to realizing
      health and non-health outcomes. We discuss the contribution of grading the
      financial burden of treatment and seamless integration of palliative care as key
      action areas regarding patients' access to and appropriateness of care given
      patients' needs and preferences. 

PMID- 25981824
TI  - Age-specific epidemic waves of influenza and respiratory syncytial virus in a
      subtropical city.
AB  - Both influenza and respiratory syncytial virus (RSV) are active throughout the
      year in subtropical or tropical regions, but few studies have reported on age
      specific seasonal patterns of these viruses. We examined the age-specific
      epidemic curves of laboratory-confirmed cases of influenza A (subtyped into
      seasonal A(H1N1), A(H3N2), and pandemic virus A(H1N1)pdm09), influenza B and
      respiratory syncytial virus (RSV), in subtropical city Hong Kong from 2004 to
      2013. We found that different types and subtypes of influenza showed similar two
      peak patterns across age groups, with one peak in winter and another in
      spring/summer. Age differences were found in epidemic onset time and duration,
      but none could reach statistical significance (p > 0.05). Age synchrony was found
      in epidemic peak time for both cool and warm seasons. RSV showed less clear
      seasonal patterns and non-synchronized epidemic curves across age. In conclusion,
      age synchrony was found in influenza seasonal epidemics and the 2009 pandemic,
      but not in RSV. None of the age groups consistently appear as the driving force
      for seasonal epidemics of influenza and RSV in Hong Kong.

PMID- 25981826
TI  - The defect level and ideal thermal conductivity of graphene uncovered by residual
      thermal reffusivity at the 0 K limit.
AB  - Due to its intriguing thermal and electrical properties, graphene has been widely
      studied for potential applications in sensor and energy devices. However, the
      reported value for its thermal conductivity spans from dozens to thousands of W
      m(-1) K(-1) due to different levels of alternations and defects in graphene
      samples. In this work, the thermal diffusivity of suspended four-layered graphene
      foam (GF) is characterized from room temperature (RT) down to 17 K. For the first
      time, we identify the defect level in graphene by evaluating the inverse of
      thermal diffusivity (termed "thermal reffusivity": Theta) at the 0 K limit. By
      using the Debye model of Theta = Theta0 + C* e(-theta/2T) and fitting the Theta-T
      curve to the point of T = 0 K, we identify the defect level (Theta0) and
      determine the Debye temperature of graphene. Theta0 is found to be 1878 s m(-2)
      for the studied GF and 43-112 s m(-2) for three highly crystalline graphite
      materials. This uncovers a 16-43-fold higher defect level in GF than that in
      pyrolytic graphite. In GF, the phonon mean free path solely induced by defects
      and boundary scattering is determined as 166 nm. The Debye temperature of
      graphene is determined to be 1813 K, which is very close to the average
      theoretical Debye temperature (1911 K) of the three acoustic phonon modes in
      graphene. By subtracting the defect effect, we report the ideal thermal
      diffusivity and conductivity (kappaideal) of graphene presented in the 3D foam
      structure in the range of 33-299 K. Detailed physics based on chemical
      composition and structure analysis are given to explain the kappaideal-T profile
      by comparing with those reported for suspended graphene. 

PMID- 25981827
TI  - Cooperative Crystallization of Heterometallic Indium-Chromium Metal-Organic
      Polyhedra and Their Fast Proton Conductivity.
AB  - Metal-organic polyhedra (MOPs) or frameworks (MOFs) based on Cr(3+) are
      notoriously difficult to synthesize, especially as crystals large enough to be
      suitable for characterization of the structure or properties. It is now shown
      that the co-existence of In(3+) and Cr(3+) induces a rapid crystal growth of
      large single crystals of heterometallic In-Cr-MOPs with the [M8L12] (M=In/Cr,
      L=dinegative 4,5-imidazole-dicarboxylate) cubane-like structure. With a high
      concentration of protons from 12 carboxyl groups decorating every edge of the
      cube and an extensive H-bonded network between cubes and surrounding H2O
      molecules, the newly synthesized In-Cr-MOPs exhibit an exceptionally high proton
      conductivity (up to 5.8*10(-2) S cm(-1) at 22.5  degrees C and 98% relative
      humidity, single crystal).

PMID- 25981828
TI  - Introduction to progress and promise of epigenetics for diagnosis and therapy in
      cancer.

PMID- 25981830
TI  - Pediatric anesthesia--concerns about neurotoxicity.

PMID- 25981829
TI  - Whole exome sequencing in a case of sporadic multiple meningioma reveals shared
      NF2, FAM109B, and TPRXL mutations, together with unique SMARCB1 alterations in a
      subset of tumor nodules.
AB  - Meningiomas are common intracranial tumors derived from arachnoid cells. Multiple
      meningiomas are occasionally present even in patients with no history of
      neurofibromatosis type 2, a condition that can cause the formation of this
      neoplasm. Previous studies have shown that most multiple meningiomas are
      monoclonal in origin. In this study, exome sequencing was performed on four
      meningiomas and the corresponding peripheral blood DNA from a 61-year-old woman
      with sporadic multiple meningioma. At least three common mutational events (at
      the NF2, FAM109B, and TPRXL genes) were detected in the tumors' DNA when they
      were compared with the lymphocyte DNA from the patient as control. Additionally,
      an array of unique mutations was detected in each tumor, including in SMARCB1 in
      two of the samples, a gene whose alteration leads to the development of
      meningioma. Mutations in other genes, such as IRS4, GULP1, NHSL1, and C10orf53,
      accounted for one alteration in each meningioma nodule. Our data suggest a
      monoclonal origin of the meningiomas in this patient, although the numerous
      alterations contained in each sample indicated multiple secondary variable
      changes in each tumor nodule. Whether the alterations described in this work are
      drivers of tumorigenesis or are simply passengers requires further study. 

PMID- 25981831
TI  - Reply: To PMID 25432448.

PMID- 25981832
TI  - The new oral anticoagulants in oral and maxillofacial surgery.

PMID- 25981833
TI  - Bad split: anatomic or technical problem?

PMID- 25981834
TI  - Reply: To PMID 25149670.

PMID- 25981835
TI  - An Old Man's Story.

PMID- 25981836
TI  - Effect of dexmedetomidine on preventing agitation and delirium after
      microvascular free flap surgery: a randomized, double-blind, control study.
AB  - PURPOSE: To determine whether dexmedetomidine sedation in the postanesthesia care
      unit (PACU) could decrease agitation and delirium after free flap surgery.
      MATERIALS AND METHODS: Eighty patients were randomly divided into 2 groups. In
      the experimental group, dexmedetomidine was given at an hourly infusion rate of
      0.5 MUg/kg for 1 hour before the operation was completed and continued in the
      PACU at 0.2 to 0.7 MUg/kg continuously until the next morning. In the control
      group, normal saline was given during the same periods. Patients in the 2 groups
      received sufentanil and midazolam for sedation and pain relief when necessary.
      Agitation was monitored with the Riker Sedation-Agitation Scale in the PACU and
      delirium was monitored with the Confusion Assessment Method for the Intensive
      Care Unit for 5 days postoperatively. RESULTS: The overall incidence of agitation
      was similar between the 2 groups. However, when the influence of patient shifting
      was excluded, the incidence of agitation in the dexmedetomidine group was
      apparently lower than that in the control group (10.3 vs 30%; P = .029). No
      difference was found in the occurrence of delirium between the experimental and
      control groups (5.1 vs 12.5%; P = .432). CONCLUSION: Dexmedetomidine does not
      change the overall incidence of agitation after free flap surgery; however, it
      does decrease agitation after PACU admission. It does not prevent delirium within
      5 days postoperatively.

PMID- 25981837
TI  - Increasing the accuracy of orbital reconstruction with selective laser-melted
      patient-specific implants combined with intraoperative navigation.
AB  - PURPOSE: Advances in technology have allowed increasing degrees of accuracy in
      the treatment of orbital deformities. The purpose of this study was to compare
      the accuracy of pre-bent titanium mesh (PBTM) and selective laser-melted patient
      specific implants (PSIs) in unilateral orbital reconstruction after traumatic
      injury. The authors hypothesized that selective laser-melted PSIs would more
      accurately reconstruct the orbit. MATERIALS AND METHODS: A retrospective review
      of 34 cases of primary reconstruction of unilateral orbital fractures treated
      using selective laser-melted PSIs (group 1, n = 17) or PBTM (group 2, n = 17) was
      performed. The primary outcome measurements were orbital volume excess and the
      anterior, medial, and posterior intraorbital angles. The Mann-Whitney U test was
      used to assess the difference in orbital volume and angular deviation between the
      2 groups. The level of statistical significance was set at .05. All P values were
      2-sided. RESULTS: The comparison of mean values for the 2 groups showed
      significant differences for the anterior angle (PBTM: mean, 11.3; standard
      deviation [SD], 1.8; PSI: mean, 4.1; SD, 0.7; P = .001), but not the medial
      (PBTM: mean, 11.6; SD, 2.0; PSI: mean, 8.2; SD, 1.9; P = .170) and posterior
      (PBTM: mean, 10.8, SD, 2.8; PSI: mean, 8.2, SD, 1.4; P = .760) angles between the
      unaffected and reconstructed orbits. The postoperative difference in volume
      between the unaffected and reconstructed orbits differed significantly between
      the 2 study groups (PBTM: mean, 0.6; SD, 0.1; PSI: mean, 0.4; SD, 0.1; P = .029).
      CONCLUSION: The results of this study suggest that complex orbital fractures can
      be reconstructed with an even higher degree of accuracy with selective laser
      melted PSIs than with PBTM.

PMID- 25981838
TI  - V-stand--a versatile surgical platform for oromandibular reconstruction using a 3
      dimensional virtual modeling system.
AB  - PURPOSE: The challenge of oromandibular reconstruction (OMR) after oncologic
      resections has been repeatedly addressed in the literature. Although final
      oncologic margins can be decided only during surgery, various attempts have been
      made to create an ideal and accurate platform for OMR. The purpose of this
      article is to present the V-stand, a versatile surgical platform for OMR using a
      3-dimensional (3D) virtual modeling system. MATERIALS AND METHODS: Seventeen
      patients requiring an OMR were included in the study. A presurgical computed
      tomogram was obtained and virtual resection and reconstruction with a free
      fibular flap were planned using 3D virtual surgery software. The mandible was
      reconstructed intraoperatively using the V-stand, which served as a template for
      the lower border of the mandible and the lateral aspects of the stand were fixed
      to the proximal mandibular segments using 2-mm titanium screws. RESULTS:
      Patients' average age was 53 years (5 to 72 yr). Median follow-up was 19 months
      (2 to 35 months). All reconstructed mandibles resulted in good function and
      esthetics. CONCLUSIONS: The V-stand offers a safe and time-efficient method for
      OMR. It provides an excellent means for accurate spatial positioning of a fibular
      free flap. The V-stand preserves the original dimensions of the reconstructed
      mandible and can overcome surgical ablation modifications because it is not
      dependent on the precision of the resection, but rather provides a mold for the
      entire mandible.

PMID- 25981839
TI  - Histomorphometric and microtomographic evaluation of the effects of hyperbaric
      oxygen and systemic ozone, used alone and in combination, on calvarial defect
      healing in rats.
AB  - PURPOSE: The aim of this study was to compare the efficacy of hyperbaric oxygen
      and systemic ozone, used separately and in combination, on the healing of bone
      defects. MATERIAL AND METHODS: Sixty male Wistar rats were divided into 4 groups
      (n = 15) according to treatment (control, hyperbaric oxygen [HBO], ozone [O], and
      HBO plus O [HBO-O]) and divided further into 3 subgroups according to day of
      sacrifice (postsurgical days 5, 15, and 30). Surgery was performed under general
      anesthesia to create a critical-size bone defect (5 mm in diameter) in the
      cranium. After sacrifice, microtomographic images of all samples were recorded,
      and histomorphometric analysis was performed. RESULTS: Histologic and radiologic
      measurements showed that the values of all experimental groups were higher than
      those of the control group. Histologic scores for all experimental groups were
      statistically higher than those for the control group day 30 (O, P = .045; HBO, P
      = .049; HBO-O, P = .042). Histologic scores also were statistically higher for
      the HBO group on day 5 (P = .045) and day 15 (P = .009) compared with the control
      group. Microtomographic scores were higher for the experimental groups than for
      the control group, with statistically significant differences for group O on day
      5 (P = .033) and day 30 (P = .0045) and for group HBO on day 15 (P = .005).
      Histologic and radiologic analyses showed positive correlations. CONCLUSION:
      Within the limitations of this study, the use of hyperbaric oxygen and ozone,
      separately and in combination, were shown to be effective in increasing bone
      healing. Combined usage was no more effective in stimulating bone healing than
      separate usage.

PMID- 25981840
TI  - Immediate-type hypersensitivity reactions due to antituberculosis drugs: a
      successful readministration protocol.
AB  - BACKGROUND: Little is known about drug hypersensitivity reactions from
      antituberculosis drugs. OBJECTIVE: To determine the frequency, risk factors, and
      characteristics of immediate-type hypersensitivity reactions from first-line
      antituberculosis drugs and to evaluate the usefulness of a readministration
      protocol for culprit drugs in this group of patients. METHODS: The study
      population consisted of patients with tuberculosis who were hospitalized and
      treated in the authors' hospital in 2011. Demographics and disease and treatment
      characteristics of patients with immediate-type hypersensitivity from
      antituberculosis drugs were compared with the other patients. Culprit drugs were
      readministered gradually according to a defined protocol to patients with
      immediate-type hypersensitivity. RESULTS: Tree hundred seventy-nine patients were
      included in the study. Eighteen immediate-type hypersensitivity reactions were
      detected in 13 patients (3.43%). The only identified risk factor was female sex
      (odds ratio 4.085). Isoniazid, rifampicin, pyrazinamide, and ethambutol were
      readministered in 11 patients and rifampicin was readministered in 2 patients,
      with 6- to 8-step protocols for each drug. Only in 2 patients did allergic
      reactions with rifampicin develop during the procedure. In these patients, after
      treatment and complete remission of allergic symptoms, the last tolerated dose
      was administered and the protocol was completed with the same adjustments.
      CONCLUSION: Immediate-type allergic reactions from antituberculosis drugs are not
      rare and not related to disease or treatment characteristics. The protocols used
      in this study provide a useful and safe method for readministration of culprit
      drugs to patients with antituberculosis drug hypersensitivity.

PMID- 25981842
TI  - The relationship between first-trimester subchorionic hematoma, cervical length,
      and preterm birth.
AB  - OBJECTIVE: The objective of the study was to evaluate the association between a
      sonographically diagnosed subchorionic hematoma (SCH) in the first trimester and
      subsequent midtrimester cervical length and preterm birth. STUDY DESIGN: In this
      cohort study, 512 women with an SCH on their first-trimester ultrasound were
      compared with 1024 women without a first-trimester SCH. All women underwent
      routine transvaginal cervical length measurement between 18 and 22 weeks. Women
      with multifetal gestation, cerclage, or a uterine anomaly were excluded. A
      multivariable linear regression was performed to assess the independent
      association of SCH with cervical length, and a logistic regression was done to
      determine whether the presence of SCH was associated with preterm birth
      independent of the cervical length. RESULTS: In a univariable analysis, the
      presence of a SCH was significantly associated with a shorter mean cervical
      length as well as a cervical length less than the 10th percentile (4.27 cm vs
      4.36 cm, P = .038; 1.9% vs 0.5%, P = .006, respectively). Preterm birth also was
      more common in women with an SCH (12.5% vs 7.3%, P = .001). Even after adjusting
      for potentially confounding factors, a significant negative association existed
      between the presence of an SCH and cervical length (centimeters) (linear
      regression coefficient, -0.08; 95% confidence interval, -0.17 to -0.005). In a
      multivariable regression, SCH remained associated with preterm birth, even with
      cervical length entered into the equation as a covariate (adjusted odds ratio,
      1.58; 95% confidence interval, 1.09-2.32). CONCLUSION: First-trimester SCH is
      associated with both a shorter cervical length and preterm birth. Our data
      suggest, however, that mechanisms other than cervical shortening may be involved
      in preterm birth among women with SCH.

PMID- 25981841
TI  - The SWI/SNF chromatin remodelling complex: Its role in maintaining genome
      stability and preventing tumourigenesis.
AB  - Genes encoding subunits of the two SWI/SNF chromatin remodelling complexes (BAF
      and PBAF) are mutated in almost 20% of all human cancers. In addition to a role
      in regulating transcription, recent work from our laboratory and others
      identified roles for both complexes in DNA damage responses and the maintenance
      of sister chromatid cohesion, which may have profound impacts on genome stability
      and contribute to its role as a tumour suppressor. Here, we review some of the
      transcription-independent functions of the SWI/SNF chromatin remodelling complex
      and discuss these in light of their potential relevance to tumourigenesis. 

PMID- 25981843
TI  - Predictors of 30-day readmission and impact of same-day discharge in laparoscopic
      hysterectomy.
AB  - OBJECTIVE: The objective of the study was to identify the predischarge predictors
      of 30-day readmission and the impact of same-day discharge after laparoscopic
      hysterectomy. STUDY DESIGN: Patients undergoing only laparoscopic hysterectomy
      with or without bilateral salpingo-oophorectomy participated in the study.
      RESULTS: The 30-day readmission rate was 3.1% (277 of 8890). Factors predictive
      of higher rates of readmission were diabetes (4.4% vs 3.0%; P = .03), chronic
      obstructive pulmonary disease (8.5% vs 3.1%; P = .02), disseminated cancer (20%
      vs 3.1%; P < .001), chronic steroid use (7.1% vs 3.1%; P = .03), daily alcohol
      use of more than 2 drinks (12.5% vs 2.5%; P = .04), and bleeding disorder (10.8%
      vs 3%; P = .001). Operative factors included surgical time of 2 hours or greater
      (3.5% vs 2.7%; P = .014). After surgery, patients had a higher rate of
      readmission when they experienced any 1 or more complications prior to discharge,
      (6.9% vs 3.1%; P = .01) as well as any complication after discharge (3.6% vs
      1.6%; P = .01). Infections (35.7%) and surgical complications (24.2%) were the
      most common reasons of readmissions. Of these patients, 20.9% were discharged the
      same day (n = 1855) and had a similar rate of readmission (2.6% vs 3.2%; P =
      n.s.). Laparoscopic hysterectomy readmission score (LHRS) can be calculated by
      assigning 1 point to diabetes, chronic obstructive pulmonary disease,
      disseminated cancer, chronic steroid use, bleeding disorder, length of surgery of
      2 hours or longer, and 2 points to any postoperative complication prior to
      discharge. Readmission rates for the LHRS score were score 1 (2.4%), score 2
      (3.3%), score 3 (5.8%), or score 4 (9.5%). CONCLUSION: The overall readmission
      rate after laparoscopic hysterectomy is low. Patients discharged the same day
      have similar rates of readmission. Higher LHRS is indicative of higher rates of
      readmission and may identify a population not suitable for same-day discharge and
      in need of higher vigilance to prevent readmissions.

PMID- 25981844
TI  - Blood volume determination in obese and normal-weight gravidas: the hydroxyethyl
      starch method.
AB  - OBJECTIVE: The impact of obesity on maternal blood volume in pregnancy has not
      been reported. We compared the blood volumes of obese and normal-weight gravidas
      using a validated hydroxyethyl starch (HES) dilution technique for blood volume
      estimation. STUDY DESIGN: Blood volumes were estimated in 30 normal-weight
      (pregravid body mass index [BMI] <25 kg/m(2)) and 30 obese (pregravid BMI >35
      kg/m(2)) gravidas >34 weeks' gestation using a modified HES dilution technique.
      Blood samples obtained before and 10 minutes after HES injection were analyzed
      for plasma glucose concentrations after acid hydrolysis of HES. Blood volume was
      calculated from the difference between glucose concentrations measured in
      hydrolyzed plasma. RESULTS: Obese gravidas had higher pregravid and visit BMI
      (mean [SD]): pregravid (41 [4] vs 22 [2] kg/m(2), P = .001); visit (42 [4] vs 27
      [2] kg/m(2), P = .001), but lower weight gain (5 [7] vs 12 [4] kg, P = .001) than
      normal-weight women. Obese gravidas had similar estimated total blood volume to
      normal-weight women (8103 +/- 2452 vs 6944 +/- 2830 mL, P = .1), but lower blood
      volume per kilogram weight (73 +/- 22 vs 95 +/- 30 mL/kg, P = .007). CONCLUSION:
      Obese gravidas have similar circulating blood volume, but lower blood volume per
      kilogram body weight, than normal-weight gravidas near term.

PMID- 25981845
TI  - Differential expression of plasma microRNA in preeclamptic patients at delivery
      and 1 year postpartum.
AB  - OBJECTIVE: Preeclampsia (PE) is a hypertensive disorder of pregnancy
      characterized by widespread maternal endothelial dysfunction. Although clinical
      signs subside following delivery, long-term risks associated with PE include
      hypertension, stroke, and cardiovascular disease. MicroRNAs (miRNAs) are emerging
      as critical regulators of biological function, and while alterations to the
      miRNAome have been described in the context of pregnancy and PE, the postpartum
      implications of PE on miRNA expression is unknown. The goal of this study was to
      characterize circulating miRNA profiles at the time of delivery and at 1 year
      postpartum for women who did and did not develop PE. STUDY DESIGN: Using a
      targeted reverse transcription polymerase chain reaction approach, selected
      miRNAs putatively involved in the pathophysiology of PE were examined in 17
      normotensive control and 13 PE maternal plasma samples at the time of delivery
      and 1 year postpartum. Ingenuity Pathway Analysis was used to map putative
      messenger RNA targets of differentially expressed miRNA to global molecular
      networks based on gene function. RESULTS: Significant increases (P < .05) in 7
      miRNAs with antiangiogenic, inflammatory, and apoptotic functions (miR-98-5p, miR
      222-3p, miR-210-3p, miR-155-5p, miR-296-3p, miR-181a-5p, miR-29b-3p) were evident
      in maternal plasma at the time of severe PE compared to time-matched controls.
      Plasma samples from individuals who developed mild PE exhibited no changes
      compared to control samples for the subset of miRNAs analyzed here. Differential
      expression of plasma miRNA at the time of delivery for women with PE were largely
      resolved at 1 year postpartum, and reduced expression of only miR-221-3p (P <
      .05) was evident. Network analysis of putative targets of differentially
      regulated miRNA identified 11 interacting networks with enrichment for proteins
      involved in cardiovascular disease, organ system development and function, and
      cell signaling and interaction. CONCLUSION: The systemic effect of PE on maternal
      systems is evident in the circulating miRNAome with substantial alterations in
      miRNA expression in women who develop severe PE. In addition we provide novel
      evidence of disruption to miR-221 expression 1 year postpartum following a
      pregnancy complicated by PE compared to normotensive time-matched controls, which
      may allude to persistent inflammation in these women after delivery.

PMID- 25981847
TI  - Relationship between obstetricians' cognitive and affective traits and delivery
      outcomes among women with a prior cesarean.
AB  - OBJECTIVE: We sought to investigate the relationship between obstetricians'
      cognitive traits and delivery outcomes among women with a prior cesarean
      delivery. STUDY DESIGN: A total of 94 obstetricians completed 5 standardized
      psychometric scales: Reflective Coping, Proactive Coping, Multiple Stimulus Types
      Ambiguity Tolerance (MSTAT), Need for Cognition, and State-Trait Anxiety
      Inventory. Scores were analyzed by quartile. Delivery data were collected for
      primiparas with 1 prior low transverse cesarean delivery and a term, cephalic
      singleton. We used chi(2) tests and random effects logistic regression to examine
      the relationship between obstetricians' cognitive traits and their patients'
      frequency of trial of labor after cesarean (TOLAC) and vaginal birth after
      cesarean (VBAC). RESULTS: Of 1502 eligible patients, 22.6% underwent TOLAC. Women
      were more likely to undergo TOLAC when cared for by physicians with scores in the
      highest quartile of the proactive coping (33.6% vs 19.6%; P < .001), MSTAT (29.2%
      vs 21.0%; P = .002), and Need for Cognition (27.9% vs 21.5%; P = .02)
      assessments, or in the lowest quartile for anxiety assessment (28.0% vs 20.6%; P
      = .001). Similarly, those with high proactive coping (18.0% vs 11.3%; P = .001),
      high MSTAT (16.6% vs 11.8%; P = .03), and low anxiety (19.2% vs 10.4%; P < .001)
      had greater VBAC rates. Random effects regression analyses revealed physicians
      with high proactive coping remained significantly more likely to have patients
      undergo TOLAC (adjusted odds ratio, 1.86; 95% confidence interval, 1.10-3.14) and
      those with low anxiety remained significantly more likely to have patients
      experience VBAC (adjusted odds ratio, 2.08; 95% confidence interval, 1.28-3.37).
      CONCLUSION: There is an increased likelihood of TOLAC and VBAC for women
      delivered by physicians with more proactive coping and less anxiety.

PMID- 25981846
TI  - Referring survivors of endometrial cancer and complex atypical hyperplasia to
      bariatric specialists: a prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to describe the acceptability of
      bariatric referrals when offered by gynecologic oncologists to women with a
      history of complex atypical hyperplasia or early-stage endometrial cancer and to
      detail compliance with referrals and weight loss attempts that are initiated 3
      months after the referral. STUDY DESIGN: Obese women with complex atypical
      hyperplasia or early-stage endometrial cancer were approached for inclusion in
      this prospective cohort study. Those women who were not in the care of a
      bariatric specialist were offered a medical referral with or without a surgical
      referral. A survey was administered at inclusion and after 3 months. RESULTS: Of
      121 women who were approached, 106 women were consented. Women reported that it
      was acceptable for their gynecologic oncologist to discuss weight loss (91.09%)
      and that a 10% loss of body weight would be beneficial (86.14%). Six women were
      already in the care of a bariatric specialist. Of the remaining 100 women, 43
      accepted a referral: 35 of 100 medical and 8 of 66 surgical referrals that were
      offered. At 3 months, 17 women complied with a referral (16 medical and 1
      surgical), and 59 women had initiated any weight loss attempt. On multivariate
      analysis, a higher initial weight (P = .0403), Charlson Comorbidity Index >=5 (P
      = .0278), and shorter time from surgery to bariatric referral (P = .0338)
      predicted acceptance of a referral. CONCLUSION: Weight-loss counseling is well
      received by these women. After being offered bariatric referral, only 17% comply,
      but most women (59%) subsequently initiate a weight loss attempt. Referrals
      should be offered early in the course of cancer care to maximize acceptance.

PMID- 25981848
TI  - The use of mechanical bowel preparation in laparoscopic gynecologic surgery: a
      decision analysis.
AB  - OBJECTIVE: The use of mechanical bowel preparation prior to laparoscopy is common
      in gynecology, but its use may affect the rates of perioperative events and
      complications. Our objective was to compare different mechanical bowel
      preparations using decision analysis techniques to determine the optimal
      preparation prior to laparoscopic gynecological surgery. STUDY DESIGN: A decision
      analysis was constructed modeling perioperative outcomes with the following
      mechanical bowel preparations: magnesium citrate, sodium phosphate, polyethylene
      glycol, enema, and no bowel preparation. Comparisons were made using published
      utility values. Secondary analyses included the percentages that had 1 or more
      preoperative events and 1 or more intra- or postoperative complications. RESULTS:
      Overall, the highest utility values were for no bowel preparation (0.98) and
      magnesium citrate (0.97), whereas the other values were as follows: enema (0.95),
      sodium phosphate (0.94), and polyethylene glycol (0.91). The difference between
      no bowel preparation and magnesium citrate was less than the published minimally
      important differences for utilities, so there is likely no real difference
      between these strategies. The probability of having at least 1 preoperative event
      was lowest for no bowel preparation (1%), whereas the probability of having at
      least 1 intra- or postoperative complication was lowest with magnesium citrate
      (8%). CONCLUSION: The highest utilities were seen with no bowel preparation, but
      the absolute difference between no bowel preparation and magnesium citrate was
      less than the minimally important difference. With similar overall utilities, our
      model raises questions as to whether mechanical bowel preparation is a necessary
      step prior to laparoscopic gynecological surgery. However, if a surgeon prefers a
      bowel preparation, magnesium citrate is the preferred option.

PMID- 25981849
TI  - MRI evaluation of maternal cardiac displacement in pregnancy: implications for
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: The purpose of this study was to determine, with the use of cardiac
      magnetic resonance imaging, whether there is vertical displacement of the heart
      during pregnancy. Cardiopulmonary resuscitation guidelines during pregnancy
      recommend placing the hands 2-3 cm higher on the sternum than in nonpregnant
      individuals. This recommendation is based on the presumption that the heart is
      displaced superiorly by the diaphragm during the third trimester. Whether there
      is true cardiac displacement because of the expanding uterus in pregnancy remains
      unknown. STUDY DESIGN: A total of 34 healthy female volunteers 18-35 years old
      were enrolled prospectively from 2010-2012 at 2 tertiary care centers. The
      conditions of all participants were evaluated with cardiac magnetic resonance
      imaging in the one-half left lateral decubitus position during the third
      trimester of pregnancy and again at a minimum of 3 months after delivery
      (surrogate for the nonpregnant state). Superior displacement of the heart was
      determined by measurement of the distance between the inferior aspect of the
      clavicular heads and the coronary sinus at both time points. RESULTS: The study
      population included 34 women (mean age, 29 +/- 3 years; body mass index, 24 +/- 4
      kg/m(2)). The mean gestational age at third-trimester imaging was 237 +/- 16 days
      (34 weeks +/- 16 days); the mean number of days for postpartum imaging (baseline)
      was 107 +/- 25 days (16 weeks +/- 25 days). There was no statistical difference
      between the cardiac position at baseline (10.1 +/- 1.2 cm) and during the third
      trimester (10.3 +/- 1.1 cm; P = .22). CONCLUSION: Contrary to popular assumption,
      there is no significant vertical displacement of the heart in the third trimester
      of pregnancy relative to the nonpregnant state. Accordingly, there is no need to
      alter hand placement for chest compressions during cardiopulmonary resuscitation
      in pregnancy.

PMID- 25981850
TI  - Conversion of Society for Maternal-Fetal Medicine abstract presentations to
      manuscript publications.
AB  - OBJECTIVE: We sought to evaluate the rate of conversion of Society for Maternal
      Fetal Medicine (SMFM) annual meeting abstract presentations to full manuscript
      publications over time. STUDY DESIGN: Full manuscript publications corresponding
      to all SMFM oral abstracts 2003 through 2010 inclusive, and SMFM poster abstracts
      in 2003, 2005, 2007, and 2009 were manually searched in PubMed. An abstract was
      considered to "match" a full publication if the abstract and publication titles
      as well as main methods and results were similar and the abstract first author
      was a publication author. In cases of uncertainty, the abstract-publication match
      was reviewed by a second physician researcher. Time to publication, publication
      rates over time, and publication rates among US vs non-US authors were examined.
      PubMed identification numbers were also collected to determine if >1 abstract
      contributed to a manuscript. Data were analyzed using Wilcoxon rank sum, analysis
      of variance, t test, and logistic regression. RESULTS: In all, 3281 abstracts
      presented at SMFM over the study period, including 629 orals (63 main plenary, 64
      fellows plenary, 502 concurrent), were reviewed. Of 3281, 1780 (54.3%) were
      published, generating 1582 unique publications. Oral abstracts had a consistently
      higher rate of conversion to publications vs posters (77.1% vs 48.8%, P < .001).
      The median time to publication was 19 (interquartile range, 9-36) months, and was
      significantly shorter for orals vs posters (11 vs 21 months, P < .001). Over the
      study period, rates of publication of orals remained constant, but rates of
      publication of posters were lower in 2007 and 2009 compared to 2003 and 2005.
      Publications related to SMFM abstracts were published in 194 different journals,
      most commonly American Journal of Obstetrics and Gynecology (39.8%), Obstetrics
      and Gynecology (9.7%), and Journal of Maternal-Fetal and Neonatal Medicine
      (6.5%). Publication rates were higher if the abstract's first author was
      affiliated with a non-US institution (64.8% vs 51.1%, P < .001) and if the
      abstract received an award (82.7% vs 53.3%, P < .001). In regression models, oral
      presentation at SMFM, first author affiliation with a non-US institution,
      submission for American Journal of Obstetrics and Gynecology SMFM special issue,
      and year of abstract presentation at SMFM were associated with full manuscript
      publication. CONCLUSION: From 2003 through 2010, full manuscript publication
      rates of SMFM abstracts were high and consistent, and time to publication
      decreased/improved across the study period for oral presentations.

PMID- 25981851
TI  - The risk of fetal death in nonanomalous pregnancies affected by polyhydramnios.
AB  - OBJECTIVE: The objective of the study was to evaluate the ongoing risk of
      intrauterine fetal demise (IUFD) in nonanomalous pregnancies affected by
      polyhydramnios. STUDY DESIGN: We analyzed a retrospective cohort of all
      singleton, nonanomalous births in California between 2005 and 2008 as recorded in
      a statewide birth certificate registry. We included all births between 24+0 and
      41+6 weeks' gestational age, excluding multiple gestations, major congenital
      anomalies, and pregnancies affected by oligohydramnios. Polyhydramnios was
      identified by International Classification of Diseases, ninth revision, codes.
      chi(2) tests were used to compare the dichotomous outcomes, and multivariable
      logistic regression analyses were then performed to control for potential
      confounders. We analyzed the data for pregnancies affected and unaffected by
      polyhydramnios. The IUFD risk was expressed as a rate per 10,000. RESULTS: The
      risk of IUFD in pregnancies affected by polyhydramnios was greater at every
      gestational age compared with unaffected pregnancies. The IUFD risk in
      pregnancies affected by polyhydramnios was more than 7 times higher than
      unaffected pregnancies at 37 weeks at a rate of 18.0 (95% confidence interval
      [CI], 9.0-32.6) vs 2.4 (95% CI, 2.0-2.5) and was 11-fold higher by 40 weeks'
      gestational age at a rate of 66.3 (95% CI, 10.8-68.6) vs 6.0 (95% CI, 5.1-6.3) in
      unaffected pregnancies. When adjusted for multiple confounding variables, the
      presence of polyhydramnios remained associated with an increased odds of IUFD in
      nonanomalous singleton pregnancies, with an adjusted odds ratio of 5.5 (95% CI,
      4.1-7.6). CONCLUSION: Ongoing risk of IUFD is greater in low-risk pregnancies
      affected by polyhydramnios at all gestational ages compared with unaffected
      pregnancies with the greatest increase in risk at term. Although further study is
      needed to explore the underlying etiology of polyhydramnios in these cases, the
      identification of polyhydramnios alone may warrant increased antenatal
      surveillance.

PMID- 25981852
TI  - Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome.
AB  - Rett syndrome, a prototypical neurological disorder caused by loss of function of
      the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2) gene, is
      associated with a severely disordered breathing pattern and reduced ventilatory
      CO2 sensitivity. In a mouse model of Rett syndrome (MeCP2 knockout), re
      introduction of the MeCP2 gene selectively in astrocytes rescues normal
      respiratory phenotype. In the present study we determined whether the metabolic
      and/or signalling functions of astrocytes are affected by testing the hypotheses
      that in conditions of MeCP2 deficiency, medullary astrocytes are unable to
      produce/release appropriate amounts of lactate or detect changes in PCO2/[H(+) ],
      or both. No differences in tonic or hypoxia-induced release of lactate from the
      ventral surface of the medulla oblongata or cerebral cortex in brain slices of
      MeCP2-knockout and wild-type mice were found. In brainstem slices of wild-type
      mice, respiratory acidosis triggered robust elevations in [Ca(2+) ]i in
      astrocytes residing near the ventral surface of the medulla oblongata. The
      magnitude of CO2 -induced [Ca(2+) ]i responses in medullary astrocytes was
      markedly reduced in conditions of MeCP2 deficiency, whereas [Ca(2+) ]i responses
      to ATP were unaffected. These data suggest that (i) metabolic function of
      astrocytes in releasing lactate into the extracellular space is not affected by
      MeCP2 deficiency, and (ii) MeCP2 deficiency impairs the ability of medullary
      astrocytes to sense changes in PCO2/[H(+) ]. Taken together with the evidence of
      severely blunted ventilatory sensitivity to CO2 in mice with conditional MeCP2
      deletion in astroglia, these data support the hypothesis of an important role
      played by astrocytes in central respiratory CO2 /pH chemosensitivity.

PMID- 25981854
TI  - The Cognitive Social Network in Dreams: Transitivity, Assortativity, and Giant
      Component Proportion Are Monotonic.
AB  - For five individuals, a social network was constructed from a series of his or
      her dreams. Three important network measures were calculated for each network:
      transitivity, assortativity, and giant component proportion. These were
      monotonically related; over the five networks as transitivity increased,
      assortativity increased and giant component proportion decreased. The relations
      indicate that characters appear in dreams systematically. Systematicity likely
      arises from the dreamer's memory of people and their relations, which is from the
      dreamer's cognitive social network. But the dream social network is not a copy of
      the cognitive social network. Waking life social networks tend to have positive
      assortativity; that is, people tend to be connected to others with similar
      connectivity. Instead, in our sample of dream social networks assortativity is
      more often negative or near 0, as in online social networks. We show that if
      characters appear via a random walk, negative assortativity can result,
      particularly if the random walk is biased as suggested by remote associations. 

PMID- 25981853
TI  - Paenibacillin A, a new 2(1H)-pyrazinone ring-containing natural product from the
      endophytic bacterium Paenibacillus sp. Xy-2.
AB  - A new 2(1H)-pyrazinone ring-containing natural product, paenibacillin A (1),
      together with five known diketopiperazine derivatives 2-6 and two known
      isoflavones 7-8, was isolated from the culture of an endophytic bacterium
      Paenibacillus sp. Xy-2. The structure of compound 1 was elucidated by extensive
      spectral methods, including UV, IR, HR-ESI-MS, 1D and 2D NMR and ECD experiments.
      Compound 1 exhibited moderate cytotoxicity against HL-60 cell line with IC50
      value of 50.48 MUM.

PMID- 25981855
TI  - Draft genome sequence of the novel strain Pseudomonas sp. 10B238 with potential
      ability to produce antibiotics from deep-sea sediment.
AB  - Pseudomonas sp. 10B238 was a putatively novel species of Pseudomonas, isolated
      from a deep-sea sediment of the South China Sea, which had the genetic potential
      to produce secondary metabolites related to nonribosomal peptides (NRPs), as well
      as showed moderate antimicrobial activities. Here we report a high quality draft
      genome of Pseudomonas sp. 10B238, which comprises 4,933,052bp with the G+C
      content of 60.23%. A total of 11 potential secondary metabolite biosynthetic gene
      clusters were predicted, including a NRP for new peptide siderophore. And many
      anaerobic respiratory terminal enzymes were found for life in deep-sea
      environments. Our results may provide insights into biosynthetic pathway for
      antimicrobial bioactive compounds and be helpful to understand the physiological
      characteristic of this species. 

PMID- 25981856
TI  - Measurement of Bacterial Bioluminescence Intensity and Spectrum: Current Physical
      Techniques and Principles.
AB  - : Bioluminescence is light production by living organisms, which can be observed
      in numerous marine creatures and some terrestrial invertebrates. More
      specifically, bacterial bioluminescence is the "cold light" produced and emitted
      by bacterial cells, including both wild-type luminescent and genetically
      engineered bacteria. Because of the lively interplay of synthetic biology,
      microbiology, toxicology, and biophysics, different configurations of whole-cell
      biosensors based on bacterial bioluminescence have been designed and are widely
      used in different fields, such as ecotoxicology, food toxicity, and environmental
      pollution. This chapter first discusses the background of the bioluminescence
      phenomenon in terms of optical spectrum. Platforms for bacterial bioluminescence
      detection using various techniques are then introduced, such as a photomultiplier
      tube, charge-coupled device (CCD) camera, micro-electro-mechanical systems
      (MEMS), and complementary metal-oxide-semiconductor (CMOS) based integrated
      circuit. Furthermore, some typical biochemical methods to optimize the analytical
      performances of bacterial bioluminescent biosensors/assays are reviewed, followed
      by a presentation of author's recent work concerning the improved sensitivity of
      a bioluminescent assay for pesticides. Finally, bacterial bioluminescence as
      implemented in eukaryotic cells, bioluminescent imaging, and cancer cell
      therapies is discussed.

PMID- 25981857
TI  - Perturbation Experiments: Approaches for Metabolic Pathway Analysis in
      Bioreactors.
AB  - In the last decades, targeted metabolic engineering of microbial cells has become
      one of the major tools in bioprocess design and optimization. For successful
      application, a detailed knowledge is necessary about the relevant metabolic
      pathways and their regulation inside the cells. Since in vitro experiments cannot
      display process conditions and behavior properly, process data about the cells'
      metabolic state have to be collected in vivo. For this purpose, special
      techniques and methods are necessary. Therefore, most techniques enabling in vivo
      characterization of metabolic pathways rely on perturbation experiments, which
      can be divided into dynamic and steady-state approaches. To avoid any process
      disturbance, approaches which enable perturbation of cell metabolism in parallel
      to the continuing production process are reasonable. Furthermore, the fast
      dynamics of microbial production processes amplifies the need of parallelized
      data generation. These points motivate the development of a parallelized approach
      for multiple metabolic perturbation experiments outside the operating production
      reactor. An appropriate approach for in vivo characterization of metabolic
      pathways is presented and applied exemplarily to a microbial L-phenylalanine
      production process on a 15 L-scale.

PMID- 25981858
TI  - Immunological factors and liver fibrosis in pediatric liver transplant
      recipients.
AB  - BACKGROUND: The aim of our study was to retrospectively assess any correlation
      between graft fibrosis and selected immunological factors in pediatric liver
      transplant recipients. MATERIAL AND METHODS: The study was performed on 33
      patients after living related donor transplantation, divided into 2 groups
      depending on history of acute rejection episodes after transplantation. We
      assessed liver biopsies for presence of fibrosis, signs of antibody-mediated
      rejection, inflammatory infiltrations, and changes in bile ducts. We correlated
      these findings with assessment of anti-HLA antibodies. RESULTS: Among 14 patients
      with ACR, a history fibrosis was found in 8 patients (57%). In 19 patients
      without a history of ACR, fibrosis was found in 9 patients (47%). Anti-HLA
      antibodies were found in 47% of patients with fibrosis and in only 18.75% of
      patients without fibrosis. Among 3 patients with signs of antibody-mediated
      rejection, all had fibrosis in the graft 2 years after transplantation. We did
      not find any patient with chronic rejection or ductopenia. CONCLUSIONS: We
      suggest that there is a correlation between ACR and development of graft fibrosis
      present in liver grafts from recipients with normal liver biochemistry. Anti-HLA
      antibodies class II seems to be most important in development of fibrosis.

PMID- 25981860
TI  - The Accuracy of Clinical Diagnosis of Oral Lesions and Patient-Specific Risk
      Factors that Affect Diagnosis.
AB  - PURPOSE: To examine the rate of discrepancy between clinical impression and
      histologic diagnosis of oral lesions in patients undergoing biopsy examination
      and to determine whether there are patient-specific variables associated with a
      higher rate of discrepancy. MATERIALS AND METHODS: The authors designed and
      implemented a retrospective cohort study that consisted of patients who underwent
      biopsy examination of oral lesions from 2005 through 2013 by oral and
      maxillofacial surgeons at the Massachusetts General Hospital. Accuracy was
      determined by comparing the clinical impression with the final histologic
      diagnosis. Clinical and histologic diagnoses were categorized as premalignant or
      malignant (group 1) or benign (group 2). The primary outcome variable was
      concordance (yes vs no) between clinical impression and histopathologic
      diagnosis. The effect of individual predictor variables (age, gender, duration,
      American Society of Anesthesiology status, cancer history, radiation therapy
      history, medications, alcohol abuse, and tobacco history) on outcome also was
      evaluated through univariate and multivariate regression analyses. RESULTS: The
      study sample was composed of 1,003 oral lesions (74 pathologically confirmed
      premalignant or malignant and 929 benign) from patients with a mean age of 44.8
      years. Of the lesions evaluated, concordance between exact clinical and
      histologic diagnoses was found in 61% of cases. Overall, the clinical impression,
      reported as benign versus premalignant or malignant, was 48.6% sensitive and
      98.1% specific. Clinicians accurately identified lesions as benign in 95.9% of
      cases. The most common of these were fibromas (positive predictive value [PPV],
      99.2%), mucoceles (PPV, 98.1%), and squamous papillomas (PPV, 96.3%). Several
      independent risk factors were associated with discrepancy: radiation therapy
      history (P = .0102), male gender (P = .0381), and patient age (P = .0468).
      CONCLUSION: The results of this study suggest that the clinical impression,
      although highly accurate for common benign conditions, is not an acceptable
      alternative to definitive biopsy findings in other cases, particularly in cases
      of premalignancy or malignancy. In addition, patients with identified independent
      risk factors (age, gender, and radiation therapy) should receive timely biopsy
      examination.

PMID- 25981859
TI  - Inhibition of MEK confers hypersensitivity to X-radiation in the context of BRAF
      mutation in a model of childhood astrocytoma.
AB  - PURPOSE: Curative therapy for childhood glioma presents challenges when complete
      resection is not possible. Patients with recurrent low-grade tumors or anaplastic
      astrocytoma may receive radiation treatment; however, the long-term sequellae
      from radiation treatment can be severe. As many childhood gliomas are associated
      with activation of BRAF, we have explored the combination of ionizing radiation
      with MEK inhibition in a model of BRAF-mutant anaplastic astrocytoma.
      EXPERIMENTAL DESIGN: The regulation of TORC1 signaling by BRAF was examined in BT
      40 (BRAF mutant) and BT-35 (BRAF wild type) xenografts, in a cell line derived
      from the BT-40 xenograft and two adult BRAF mutant glioblastoma cell lines. The
      effect of MEK inhibition (selumetinib), XRT (total dose 10 Gy as 2 Gy daily
      fractions), or the combination of selumetinib and XRT was evaluated in
      subcutaneous BT-40 xenografts. RESULTS: Inhibition of MEK signaling by
      selumetinib suppressed TORC1 signaling only in the context of the BRAF-mutant
      both in vitro and in vivo. Inhibition of MEK signaling in BT-40 cells or in
      xenografts lead to a complete suppression of FANCD2 and conferred
      hypersensitivity to XRT in BT-40 xenografts without increasing local skin
      toxicity. CONCLUSIONS: Selumetinib suppressed TORC1 signaling in the context of
      BRAF mutation. Selumetinib caused a rapid downregulation of FANCD2 and markedly
      potentiated the effect of XRT. These data suggest the possibility of potentiating
      the effect of XRT selectively in tumor cells by MEK inhibition in the context of
      mutant BRAF or maintaining tumor control at lower doses of XRT that would
      decrease long-term sequelae.

PMID- 25981861
TI  - What Is the IBCSOMS?

PMID- 25981864
TI  - We Privileged Few.

PMID- 25981863
TI  - Insurance Status, an Important Predictor of Oral Cancer Surgery Outcomes.
AB  - PURPOSE: Patients without insurance, or using Medicaid, generally have a lower
      socioeconomic status. They have less access to screening and regular medical
      care, resulting in later diagnosis of oral cancer. This study examined the
      association between insurance status and the likelihood of complications after
      head and neck cancer surgery. MATERIALS AND METHODS: A retrospective cross
      sectional study was implemented to determine whether patients' insurance status
      is associated with increased complications and length of stay after oral cancer
      surgery. Patients were grouped into 4 cohorts: 1) private insurance, 2) Medicare,
      3) Medicaid, and 4) uninsured. Patients were stratified further to consider age,
      gender, initial staging, pre-existing comorbidities, and social history. Data
      were analyzed with chi(2) test, 1-way analysis of variance, odds ratios, and
      binary logistic regression. RESULTS: This study consisted of 89 surgically
      treated patients. The uninsured and Medicaid groups had the highest incidence of
      postoperative complications. Uninsured patients, followed by the Medicare cohort,
      were the most likely to have an extended length of stay. CONCLUSION: Uninsured
      and Medicaid patients are at increased probability for major and minor
      complications after head and neck cancer surgery. Uninsured patients also showed
      the greatest tendency for a prolonged length of hospital stay. This could reflect
      their lack of preventive care, increased use of tobacco and alcohol, presentation
      with more advanced disease, and delays in initiating treatment.

PMID- 25981865
TI  - Response to Radcliffe et al.

PMID- 25981862
TI  - Use of Intraoperative Navigation for Minimally Invasive Retrieval of a Broken
      Dental Needle.
AB  - This report describes a case of needle breakage during an inferior alveolar nerve
      block to perform a restorative dental procedure on a 13-year-old patient. The
      needle was removed in a minimally invasive fashion using a Medtronic
      StealthStation S7 surgical navigation system and custom interocclusal splint to
      allow for stable, identically repeatable positioning of the mandible. This report
      adds another example of the utility of image-guided surgery for the removal of
      foreign bodies from the head and neck region in a minimally invasive fashion. 

PMID- 25981867
TI  - Mechanisms of microcystin-LR-induced cytoskeletal disruption in animal cells.
AB  - Microcystin-LR (MC-LR), a potent hepatotoxin produced by certain bloom-forming
      cyanobacteria, covalently binds to serine/threonine protein phosphatases and acts
      as an efficient inhibitor of this group of enzymes. MC-LR induces oxidative
      stress and the unfolded protein response in multiple cell types, leading to
      apoptosis through the mitochondrial and endoplasmic reticulum pathways.
      Histologic lesions of acute MC-LR toxicosis exhibit membrane blebbing, cell
      rounding and dissociation, indicating that this toxin may exert hepatotoxic
      effects by causing cytoskeletal disruption. Both in vivo and in vitro studies
      have revealed that exposure of human, mouse, or rat hepatocytes to MC-LR induces
      the rearrangement or collapse of the three components of the cytoskeleton. In
      addition, multiple cytoskeletal and cytoskeleton-associated proteins have been
      found to be affected by MC-LR. This review summarizes the increasing information
      in the literature pertaining to the molecular mechanisms of MC-LR-induced
      cytoskeletal disruption and may increase our understanding of its toxicity. 

PMID- 25981866
TI  - EPR spectroscopy of chlorpromazine-induced free radical formation in normal human
      melanocytes.
AB  - The purpose of this study was to estimate the effect of chlorpromazine on free
      radical concentration in HEMn-DP melanocytes using electron paramagnetic
      resonance (EPR) spectroscopy. It was found that chlorpromazine at concentrations
      of 1 * 10(-7) and 1 * 10(-6) M contributed to the formation of free radicals (g
      values ~2) in a dose-dependent manner. The increase in free radical formation was
      accompanied by an increase in cytotoxicity, as shown by a tetrazolium assay.
      Homogeneous broadening of EPR lines, slow spin-lattice relaxation processes, and
      strong dipolar interactions characterized all the tested cellular samples. The
      performed examination of free radical formation in cells exposed to different
      chlorpromazine concentrations confirmed the usefulness of electron paramagnetic
      resonance spectroscopy to determine the effect of a drug on free radical
      production in a cellular model system in vitro.

PMID- 25981868
TI  - Endogenous contrast T1rho cardiac magnetic resonance for myocardial fibrosis in
      hypertrophic cardiomyopathy patients.
AB  - BACKGROUND: Late gadolinium enhancement (LGE) is a standard method to evaluate
      myocardial fibrosis, but restricted due to contrast agent contraindications. Non
      contrast T1rho can generate endogenous contrast, and detect fibrosis in chronic
      myocardial infarction. However, T1rho for hypertrophic cardiomyopathy (HCM)
      patients is still unreported. The present study aimed to investigate T1rho for
      fibrotic assessment and the clinical implication in HCM patients. METHODS: 18 HCM
      patients and 8 controls underwent T1rho, cine, and LGE cardiac magnetic resonance
      (CMR). T1rho relaxation time maps were created. Left ventricular (LV) parameters
      assessed included wall thickness, wall thickening, chamber volumes, ejection
      function, and fibrotic size. New York Heart Association (NYHA) functional
      classification was conducted. RESULTS: Hyper-T1rho value was identified in 12 HCM
      patients, consistent with LGE. The mean T1rho values of controls, LGE-negative
      patients, and remote myocardium of LGE-positive patients were 42.2+/-1.6ms,
      43.9+/-2.5ms, and 42.5+/-1.2ms respectively, and these values showed no
      significant difference (all p>0.05). T1rho-3-SD and T1rho-4-SD fibrotic sizes
      (32.5+/-14.0% and 25.1+/-11.5%) did not differ from LGE fibrotic size (28.1+/
      11.2%) (both p>0.05). For the fibrotic size, T1rho-3-SD method obtained the
      strongest correlation with LGE (r=0.88, p<0.001), and T1rho-4-SD obtained the
      minimal mean difference with LGE (-3.1%; -15.2 to 9.1%), compared with other SDs.
      All the fibrotic sizes assessed by both methods correlated directly with LV
      maximal end-diastolic thickness (all p<0.05). Negative correlation was found
      between T1rho-4-SD fibrotic size and LV ejection fraction (r=-0.49, p=0.11).
      T1rho-4-SD fibrotic size showed positive correlation with NYHA class (r=0.46,
      p=0.13). CONCLUSIONS: T1rho CMR has potential to detect fibrosis in HCM patients.
      4-SD may be the appropriate threshold for assessment.

PMID- 25981869
TI  - Hyaluronic Acid/Poly-l-Lysine Multilayers as Reservoirs for Storage and Release
      of Small Charged Molecules.
AB  - Polyelectrolyte multilayer films are nowadays very attractive for bioapplications
      due to their tunable properties and ability to control cellular response. Here we
      demonstrate that multilayers made of hyaluronic acid and poly-l-lysine act as
      high-capacity reservoirs for small charged molecules. Strong accumulation within
      the film is explained by electrostatically driven binding to free charges of
      polyelectrolytes. Binding and release mechanisms are discussed based on charge
      balance and polymer dynamics in the film. Our results show that transport of
      molecules through the film-solution interface limits the release rate. The
      multilayers might serve as an effective platform for drug delivery and tissue
      engineering due to high potential for drug loading and controlled release. 

PMID- 25981870
TI  - Confined Flocculation of Ionic Pollutants by Poly(L-dopa)-Based Polyelectrolyte
      Complexes in Hydrogel Beads for Three-Dimensional, Quantitative, Efficient Water
      Decontamination.
AB  - The development of simple and recyclable adsorbents with high adsorption capacity
      is a technical imperative for water treatment. In this work, we have successfully
      developed new adsorbents for the removal of ionic pollutants from water via
      encapsulation of polyelectrolyte complexes (PECs) made from positively charged
      poly(allylamine hydrochloride) (PAH) and negatively charged poly(l-3,4
      dihydroxyphenylalanine) (PDopa), obtained via the self-polymerization of l-3,4
      dihydroxyphenylalanine (l-Dopa). Given the outstanding mass transport through the
      hydrogel host matrixes, the PDopa-PAH PEC guests loaded inside can effectively
      and efficiently remove various ionic pollutants, including heavy metal ions and
      ionic organic dyes, from water. The adsorption efficiency of the PDopa-PAH PECs
      can be quantitatively correlated to and tailored by the PDopa-to-PAH molar ratio.
      Because PDopa embodies one catechol group, one carboxyl group, and one amino
      group in each repeating unit, the resulting PDopa-PAH PECs exhibit the largest
      capacity of adsorption of heavy metal ions compared to available adsorbents.
      Because both PDopa and PAH are pH-sensitive, the PDopa-PAH PEC-loaded agarose
      hydrogel beads can be easily and completely recovered after the adsorption of
      ionic pollutants by adjusting the pH of the surrounding media. The present
      strategy is similar to the conventional process of using PECs to flocculate ionic
      pollutants from water, while in our system flocculation is confined to the
      agarose hydrogel beads, thus allowing easy separation of the resulting adsorbents
      from water. 

PMID- 25981871
TI  - Health complaints and wind turbines: The efficacy of explaining the nocebo
      response to reduce symptom reporting.
AB  - BACKGROUND: A number of people are reporting an environmental sensitivity to sub
      audible windfarm sound (infrasound), characterised by the experience of recurrent
      non-specific symptoms. A causal link between exposure and symptoms is not
      indicated by empirical evidence. Research indicates symptoms may be explained by
      the nocebo response, whereby health concerns and negative expectations, created
      from social discourse and media reports, trigger symptom reporting. OBJECTIVE:
      The experimental aim was to test whether providing a nocebo explanation for
      symptoms, to individuals reporting symptomatic experiences during infrasound
      exposure, would ameliorate symptoms during further exposure. METHOD: Sixty-six
      volunteers were randomly assigned to nocebo explanation or biological explanation
      groups. Participants were concurrently exposed to infrasound and audible windfarm
      sound, while reporting on current symptoms and mood, during two exposure
      sessions. Preceding session one, participants watched a presentation integrating
      media warnings about purported health risks posed by windfarm infrasound. Before
      session two, nocebo explanation participants viewed material outlining how nocebo
      responding could explain symptom reporting. Instead biological explanation
      participants watched material presenting pathophysiological theories for
      symptoms. RESULTS: During session one, participants reported increased symptoms
      and mood deterioration from baseline assessment. During session two symptom
      reporting and mood deterioration was maintained by biological explanation
      participants, while mood and symptoms reported by nocebo explanation participants
      returned to baseline levels. CONCLUSION: Results indicate that providing an
      explanation of the nocebo response, followed by exposure to infrasound, has the
      potential to operate as an intervention to reduce symptomatic experiences in
      people reporting symptoms attributed to windfarm generated infrasound.

PMID- 25981872
TI  - Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels
      of placental tissue, maternal and umbilical cord blood.
AB  - Human hemochromatosis protein (HFE), a major histocompatibility complex class I
      like integral membrane protein, participates in the down regulation of intestinal
      iron absorption by binding to transferrin receptor (TR). HFE competes with
      transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On
      the other hand, a lack of HFE increases the intestinal absorption of iron
      similarly to iron deficiency associated with increasing in absorption and
      deposition of lead. During pregnancy, placenta cannot prevent transfer lead to
      the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in
      children. The aim of this study was to determine the association between the
      maternal HFE H63D single-nucleotide polymorphism and lead levels in placental
      tissue, maternal blood and umbilical cord bloods. The study population comprised
      93 mother-placenta pairs. Venous blood from mother was collected to investigate
      lead levels and HFE polymorphism that was detected by standard PCR-RFLP
      technique. Cord bloods and placentas were collected for lead levels which were
      analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype
      frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6%
      heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed
      that the placental tissue, umbilical cord and maternal blood lead levels of
      mothers with HD+DD genotypes were significantly higher than those with HH
      genotype (p<0.05). The present study indicated for the first time that mothers
      with H63D gene variants have higher lead levels of their newborn's placentas and
      umbilical cord bloods. 

PMID- 25981873
TI  - Bio-Enabled Gold Superstructures with Built-In and Accessible Electromagnetic
      Hotspots.
AB  - The bio-enabled synthesis of a novel class of surface enhanced Raman scattering
      probes is presented for functional imaging with built-in and accessible
      electromagnetic hotspots formed between densely packed satellites grown on a
      plasmonic core. The superstructures serve as nanoscale sensors to
      spatiotemporally map intravesicular pH changes along endocytic pathways inside
      live cells. 

PMID- 25981874
TI  - Deltamethrin, a pyrethroid insecticide, could be a promising candidate as an
      anticancer agent.
AB  - Cancer is the one of the leading causes of death, whose incidences is increasing
      day by day. Various types of anticancer agents are used for its treatment, but
      unfortunately none of them is able to treat the cancer. Thus, the exploration of
      novel mechanistic pathways of existing molecules may help to develop more
      effective anticancer agents. Deltamethrin, at low concentration, is a safe
      pyrethroid insecticide that is widely used in the agriculture and home pest
      control. Recent in vitro and in vivo studies have shown that the deltamethrin
      have the potential to induce apoptogenic signaling pathways which plays an
      important role in the mechanism of anticancer action. Thus, deltamethrin thereof
      could have the potential to develop as an anticancer agent. Further both in vitro
      and in vivo evaluation of the therapeutic and toxic effects of this compound is
      needed for starting of clinical trial. 

PMID- 25981875
TI  - Anorexia nervosa, seasonality, and polyunsaturated fatty acids.
AB  - Anorexia nervosa is a serious neurobehavioral disorder marked by semistarvation,
      extreme fear of weight gain, frequently hyperactivity, and low body temperature.
      The etiology remains unknown. We present a speculation that a primary causative
      factor is that polyunsaturated fatty acids are skewed to prevent oxidative damage
      in phospholipid membranes. This causes a change in the trade off of oxidation
      protection vs homeoviscous adaptation to lower temperatures, which sets off a
      metabolic cascade that leads to the rogue state of anorexia nervosa. 

PMID- 25981876
TI  - An electronic approach to minimising moisture-associated skin damage in ostomy
      patients.
AB  - Marked developments in the design of ostomy appliances in recent years have
      revolutionised stoma care and management but the prevalence of peristomal skin
      complications continues to be problematic with incidence rates ranging from 10%
      to 70%. Despite requisite pre and post-operative education for new patients,
      complications continue to arise - even under the close supervision of specialist
      nurses. Prolonged exposure of the skin to high pH stoma effluent is widely
      accepted as a key contributor to the onset of moisture-associated skin disease
      and it is our hypothesis that a "smart wafer", employing electrochemical
      manipulation of local pH, could mitigate some of the issues currently plaguing
      ostomy management. Current electrochemical research strategies translatable to
      stoma care are presented and their possible implementations critically appraised.

PMID- 25981877
TI  - Metformin as possible therapy of pulmonary arterio venous malformation in HHT
      patients.
AB  - Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an
      autosomic dominant disorder, which is characterized by the development of
      multiple arteriovenous malformations. Pulmonary arteriovenous malformations may
      either rupture or be responsible for a right-to-left shunting leading to
      paradoxical embolism causing stroke or cerebral abscess. Metformin may harbor a
      pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other
      mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing
      negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either
      directly or via the AMPK pathway and preventing from pulmonary hypertension
      development and (d) diminushin oxidative stress. An animal model could be
      experimented to show its effects on PAVM formation. Metformin could also be
      tested in human individuals, particularly in patients presenting a diffuse HHT
      type with tiny PAVM. Metformin may be indicated as a prophylactic or curative
      therapy in HHT patients presenting with initial lung involvement. Metformin may
      be proposed to prevent from pulmonary arteriovenous malformation development and
      subsequent related complications. 

PMID- 25981878
TI  - The effects of chronic exercise training status on motor unit activation and
      deactivation control strategies.
AB  - This study examined the mechanomyographic (MMGRMS) amplitude-force relationships
      for 5 (age = 19.20 +/- 0.45 years) aerobically trained (AT), 5 (age = 25 +/- 4.53
      years) resistance-trained (RT) and 5 (age = 21.20 +/- 2.17 years) sedentary (SED)
      individuals. Participants performed an isometric trapezoidal muscle action at 60%
      maximal voluntary contraction of the leg extensors that included linearly
      increasing, steady force, and linearly decreasing muscle actions. MMG and
      skinfold thickness were recorded from the vastus lateralis. b and a terms were
      calculated from the natural log-transformed MMGRMS-force relationships (linearly
      increasing and decreasing segments) for each participant. An average of MMGRMS
      was calculated for the entire steady force segment. The b terms for the RT (0.727
      +/- 0.334) and SED (0.622 +/- 0.281) were significantly greater (P < 0.05) than
      the AT (0.159 +/- 0.223) and were greater during the linearly increasing (0.622
      +/- 0.426) than decreasing (0.383 +/- 0.269) segments when collapsed across
      segments and training status, respectively. MMGRMS during the steady force
      segment and skinfold thicknesses were not different among training statuses (P =
      0.106, P = 0.142). Motor unit (MU) activation strategies were influenced as a
      function of exercise training status and muscle action. Future research is needed
      to fully understand the implications of these changes in MU control strategies as
      a result of chronic exercise training on exercise and athletic performance.

PMID- 25981879
TI  - Baicalein attenuates renal fibrosis by inhibiting inflammation via down
      regulating NF-kappaB and MAPK signal pathways.
AB  - Baicalein is a natural flavonoid that possesses notable anti-inflammatory
      effects. In this study, we detected whether baicalein protects against
      inflammatory response in unilateral ureteral obstruction mice model to ameliorate
      tubulointerstitial fibrosis. Baicalein treatment significantly attenuated
      tubulointerstitial fibrosis by markedly reducing fibronectin and collagen-I. The
      downregulation of alpha-smooth muscle actin and upregulation of E-cadherin
      indicated that the epithelial-mesenchymal transition process was suppressed.
      Furthermore, baicalein administration blocked the infiltration of macrophages and
      lymphocytes, as evidenced by the significantly reduced CD68 and CD3 positive
      cells. Meanwhile, the mRNA expression of the pro-inflammatory cytokines tumor
      necrosis factor-alpha, interleukin-1beta, and monocyte chemotactic protein in
      baicalein-treated groups was markedly reduced compared with the vehicle-treated
      group. More importantly, unilateral ureteral obstruction induced the activation
      of NF-kappaB and mitogen-activated protein kinase signal pathways to switch on
      inflammatory response to aggravate kidney fibrosis, but these effects were
      mitigated by baicalein. These data demonstrate that baicalein could inhibit
      inflammatory process via inactivation of NF-kappaB and MAPK signal pathways to
      execute its anti-fibrotic actions in obstructive kidney disease. 

PMID- 25981881
TI  - A cross-hospital cost and quality assessment system by extracting frequent
      physician order set from a nationwide Health Insurance Research Database.
AB  - PURPOSE: Clinical pathways fall under the process perspective of health care
      quality. For care providers, clinical pathways can be compared to improve health
      care quality. The objective of this study was to design a convenient physician
      order set comparison system based on claim records from the National Health
      Insurance Research Database (NHIRD) of Taiwan. METHODS: Data were retrieved from
      the NHIRD for the period of 2003-2007 for frequent physician order sets found in
      hospital surgical hernia repair inpatient claim records. The derived frequent
      physician order sets were divided into five frequency thresholds: 80%, 85%, 90%,
      95% and 100%. A consistency index was defined and calculated to understand each
      care providers' adherence to clinical pathways. In addition, the average count of
      physician orders, average amount of cost, Charlson comorbidity index, and
      recurrence rate were calculated; these variables were considered in frequent
      physician order sets comparison. RESULTS: Records for 3262 patients from 257
      hospitals were retrieved. The frequent physician order sets of various frequency
      thresholds, Charlson comorbidities, and recurrence rates were extracted and
      computed for comparison among hospitals. A recurrence rate threshold of 2% was
      established to separate low and high quality of herniorrhaphy at each hospital.
      Univariable analysis showed that low recurrence rate was associated with high
      consistency index (70.99+/-23.88 vs. 52.60+/-20.30; P<.001), few surgeons at each
      hospital (3.50+/-4.41 vs. 7.09+/-6.57; P<.001), and non-medical center facility
      type (P=.042). A multivariable Cox regression analysis indicated an association
      of low recurrence rates with consistency index only (one percentage increased:
      OR=0.973; CI: 0.957-0.990; P=.002). CONCLUSIONS: The proposed system leveraged
      the claim records to generate frequent physician order sets at hospitals, thus
      solving the difficulty in obtaining clinical pathway data. This allows medical
      professionals and management to conveniently and effectively compare and query
      similarities and differences in clinical pathways among hospitals.

PMID- 25981880
TI  - The role of Cyclin G1 in cellular proliferation and apoptosis of human epithelial
      ovarian cancer.
AB  - Cyclin G1 plays an essential role in the development of human carcinoma. Here, we
      characterized the clinical significance of Cyclin G1 and investigated its role in
      cellular proliferation and apoptosis of epithelial ovarian cancer (EOC). Western
      blot was used to evaluate the expression of Cyclin G1 in nine fresh EOC tissues
      and three fresh normal ovarian tissues. Immunohistochemistry analysis was
      performed on formalin-fixed paraffin-embedded section of 119 cases of EOCs. Using
      cell counting kit (CCK)-8 and colony formation assays, we analyzed the effect of
      Cyclin G1 in cellular proliferation of EOC. Besides, the immunofluorescence and
      flow cytometry analysis was performed to study the role of Cyclin G1 in cellular
      apoptosis of EOC. We found Cyclin G1 was up-regulated in EOC tissues compared
      with the normal ovary tissues. Cyclin G1 expression in EOC was closely correlated
      with differentiation grade (P = 0.009) and malignant tumor cells in ascites (P =
      0.009). The Kaplan-Meier curve showed that higher expression of Cyclin G1 was
      associated with significantly shorter survival in EOC patients. Multivariate
      analysis suggested Cyclin G1 expression was an independent prognostic factor for
      overall survival. CCK-8 and colony formation assays revealed that depletion of
      Cyclin G1 inhibited the proliferation and clone formation. Combined
      immunofluorescence and flow cytometry analysis showed that silencing of Cyclin G1
      with shRNA could promote apoptosis of ovarian cancer cells. Additionally, the
      result of immunoprecipitation test showed Cyclin G1 interacted with CDK2 in EOC
      cells. In summary, our findings suggest that Cyclin G1 may be involved in the
      prognosis of EOC patients and be a useful therapeutic target for EOC.

PMID- 25981882
TI  - Longlook: initial outcomes of a longitudinal integrated rural clinical placement
      program.
AB  - OBJECTIVE: To assess outcomes in terms of academic performance and subsequent
      career choice in medical students undertaking a longitudinal integrated rural
      clinical placement. DESIGN: This was a retrospective, observational, cohort
      study. SETTING: The 'Longlook' program is a longitudinal integrated rural
      clinical placement run collaboratively by Griffith University, Queensland Rural
      Medical Education and Queensland Health as part of the Griffith medical program.
      PARTICIPANTS: Participants in this study were students completing years 3 and 4
      in the Griffith medical program between 2010 and 2013. Assessment data were
      available for 683 participants, and internship location was available for all 472
      students allocated within Queensland (87% of graduated students). INTERVENTIONS:
      Introduction of Longlook program. MAIN OUTCOME MEASURES: The primary outcome
      measures were performance in overall and clinical assessments, and intern
      location (rural versus urban). RESULTS: When performance in prior year was taken
      into account, there were no statistically significant differences in academic
      performance in year 3 or 4 for rural and urban students. Of Longlook students who
      have graduated, 31/46 (67%) have undertaken internship at a rural location
      compared with 63/426 (15%) for urban hospital-based students (odds ratio 11.91;
      95% confidence interval 6.08-23.32). CONCLUSIONS: We have demonstrated that it is
      feasible to implement a parallel longitudinal integrated rural clinical placement
      in an established conventional postgraduate medical program and provide similar
      learning outcomes. Initial findings suggest that this experience is translating
      into positive outcomes in terms of future careers in rural settings. There is a
      need to reappraise the structure of initiatives aimed at promoting rural careers
      in medicine.

PMID- 25981883
TI  - Dangers of vaccine refusal near the herd immunity threshold: a modelling study.
AB  - BACKGROUND: Childhood vaccination remains the focus of heated public debate.
      Parents struggle to understand the potential risks associated with vaccination
      but both parents and physicians assume that they understand the risks associated
      with infection. This study was done to characterise how modern vaccination
      practices have altered patient risks from infection. METHODS: In this modelling
      study, we use mathematical analysis to explore how modern-era vaccination
      practices have changed the risks of severe outcomes for some infections by
      changing the landscape for disease transmission. We show these effects using
      published data from outbreaks in the USA for measles, chickenpox, and rubella.
      Calculation of risk estimation was the main outcome of this study. FINDINGS: Our
      calculations show that negative outcomes are 4.5 times worse for measles, 2.2
      times worse for chickenpox, and 5.8 times worse for rubella than would be
      expected in a pre-vaccine era in which the average age at infection would have
      been lower. INTERPRETATION: As vaccination makes preventable illness rarer, for
      some diseases, it also increases the expected severity of each case. Because
      estimates of case risks rely on data for severity generated during a pre-vaccine
      era they underestimate negative outcomes in the modern post-vaccine
      epidemiological landscape. Physicians and parents should understand when making
      decisions about their children's health and safety that remaining unvaccinated in
      a predominantly vaccine-protected community exposes their children to the most
      severe possible outcomes for many preventable diseases. FUNDING: None.

PMID- 25981884
TI  - Herd immunity and the herd severity effect.

PMID- 25981885
TI  - Bovine in vitro reproduction models can contribute to the development of (female)
      fertility preservation strategies.
AB  - Recent increases in the number of successful cancer treatments have stimulated
      interest in fertility preservation strategies in women of reproductive age and in
      prepubertal girls. However, research on the application of such programs under
      clinical conditions suffers from the scarce availability of human tissue for
      research purposes and from concurrent relevant ethical issues. To partly address
      this problem, this review focuses on the possibilities of ruminant in vitro
      models providing additional insights into several aspects of fertility
      preservation, ranging from preantral follicle collection to oocyte and follicle
      cryopreservation, to noninvasive quality assessment, and to follicle culture.
      After a brief introduction, we discuss currently available techniques involved in
      (human) fertility preservation, together with their inherent advantages and
      limitations. On the basis of literature, we describe specific points for
      improvement or urgent additional research, such as (1) the lack of noninvasive
      methods to assess viability and developmental capacity of preantral follicles
      (either isolated or "in situ"); (2) autotransplantation and cryopreservation of
      ovarian cortex and follicles; (3) ischemia, follicular burnout, and graft
      rejection as major causes of preantral follicle loss; and (4) the development of
      routine in vitro follicle culture methods. Within each section, an overview is
      given of similar available techniques in (ruminant) assisted reproduction, with
      suggestions as to where and how these research models might contribute to fill
      the identified gaps. After the identification of the remaining issues in the
      development of integrated fertility preservation strategies, available ruminant
      in vitro models are introduced, described, and matched to these challenges to
      define common grounds for reproductive research. Ruminant in vitro models are
      increasingly considered as being very relevant for human preimplantation
      reproductive research. Because ruminant in vitro models are not hampered by
      restrictive ethical constraints, they will undoubtedly boost research progress in
      fertility preservation. At the end of the review, future common research goals
      are proposed through which human and animal scientists can meet and hasten the
      development of integrated fertility preservation strategies. 

PMID- 25981886
TI  - Current methods for the synthesis of homogeneous antibody-drug conjugates.
AB  - Development of efficient and safe cancer therapy is one of the major challenges
      of the modern medicine. Over the last few years antibody-drug conjugates (ADCs)
      have become a powerful tool in cancer treatment with two of them, Adcetris(r)
      (brentuximab vedotin) and Kadcyla(r) (ado-trastuzumab emtansine), having recently
      been approved by the Food and Drug Administration (FDA). Essentially, an ADC is a
      bioconjugate that comprises a monoclonal antibody that specifically binds tumor
      surface antigen and a highly potent drug, which is attached to the antibody via
      either cleavable or stable linker. This approach ensures specificity and efficacy
      in fighting cancer cells, while healthy tissues remain largely unaffected.
      Conventional ADCs, that employ cysteine or lysine residues as conjugation sites,
      are highly heterogeneous. This means that the species contain various populations
      of the ADCs with different drug-to-antibody ratios (DARs) and different drug load
      distributions. DAR and drug-load distribution are essential parameters of ADCs as
      they determine their stability and efficacy. Therefore, various drug-loaded forms
      of ADCs (usually from zero to eight conjugated molecules per antibody) may have
      distinct pharmacokinetics (PK) in vivo and may differ in clinical performance.
      Recently, a significant progress has been made in the field of site-specific
      conjugation which resulted in a number of strategies for synthesis of the
      homogeneous ADCs. This review describes newly-developed methods that ensure
      homogeneity of the ADCs including use of engineered reactive cysteine residues
      (THIOMAB), unnatural amino acids, aldehyde tags, enzymatic transglutaminase- and
      glycotransferase-based approaches and novel chemical methods. Furthermore, we
      briefly discuss the limitation of these methods emphasizing the need for further
      improvement in the ADC design and development.

PMID- 25981887
TI  - Novel thermosensitive in situ gel based on poloxamer for uterus delivery.
AB  - Side effects and drug residues are major concerns affecting hormone therapy of
      bovine reproductive diseases. Fertility-promoting intrauterine infusion liquid
      (FPL), an effective alternative to hormone therapy, is associated with short
      retention time and low therapeutic efficacy. To address these problems, we
      developed a thermosensitive in situ gel based on poloxamer 407 for local uterine
      administration. To achieve the desired gelling temperature and enhance local
      retention property, we added poloxamer 188 and HPMC to the formulation containing
      poloxamer 407 and FPL. After screening was performed, the optimized formulation
      showed good temperature sensitivity in vitro and in vivo. Gelation temperature
      was approximately 27 degrees C. In vitro release tests showed that icariin (the
      major active compound in FPL) was slow released from in situ forming gel. After
      the gel was locally administered, uterine and ovarian indexes were significantly
      increased in the gel group compared with the control group (P<0.05). The serum
      estradiol level of the gel group was significantly higher than that of the
      control group (P<0.01). Histological evaluation did not show mucosa irritation in
      the gel group. Therefore, the proposed in situ forming gel system based on
      poloxamer 407 is a promising local drug delivery system to treat bovine uterine
      diseases. 

PMID- 25981888
TI  - Strain induced fragility transition in metallic glass.
AB  - Relaxation dynamics are the central topic in glassy physics. Recently, there is
      an emerging view that mechanical strain plays a similar role as temperature in
      altering the relaxation dynamics. Here, we report that mechanical strain in a
      model metallic glass modulates the relaxation dynamics in unexpected ways. We
      find that a large strain amplitude makes a fragile liquid become stronger,
      reduces dynamical heterogeneity at the glass transition and broadens the loss
      spectra asymmetrically, in addition to speeding up the relaxation dynamics. These
      findings demonstrate the distinctive roles of strain compared with temperature on
      the relaxation dynamics and indicate that dynamical heterogeneity inherently
      relates to the fragility of glass-forming materials. 

PMID- 25981890
TI  - A potent and selective calcitonin gene-related peptide (CGRP) receptor
      antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation:
      Role of CGRP in orofacial pain.
AB  - Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal
      distribution, which involve the masticatory musculature, the temporomandibular
      joint or both. Their pathophysiology remains unclear, as inflammatory mediators
      are thought to be involved, and clinically TMD presents pain and sometimes
      limitation of function, but often appears without gross indications of local
      inflammation, such as visible edema, redness and increase in temperature.
      Calcitonin gene-related peptide (CGRP) has been implicated in other pain
      disorders with trigeminal distribution, such as migraine, of which TMD shares a
      significant co-morbidity. CGRP causes activation and sensitization of trigeminal
      primary afferent neurons, independent of any inflammatory mechanisms, and thus
      may also be involved in TMD. Here we used a small molecule, selective CGRP
      receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous
      nociceptive facial grooming behaviors, neuronal activation in the trigeminal
      nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of
      acute orofacial masseteric muscle pain that we have developed, as a surrogate of
      acute TMD. We show that CFA masseteric injection causes significant spontaneous
      orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and
      release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a
      significant reduction in these spontaneous orofacial pain behaviors. Also, at 2
      and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal
      nucleus, used as a marker of neuronal activation, was much lower on both
      ipsilateral and contralateral sides after pre-treatment with MK-8825. There was
      no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be
      involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in
      the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic
      efficacy in the treatment of TMD, as they do with migraine. 

PMID- 25981891
TI  - Early bronchiolitis obliterans syndrome shows an abnormality of perfusion not
      ventilation in lung transplant recipients.
AB  - Long-term survival of lung transplant patients is limited, principally because of
      Bronchiolitis Obliterans Syndrome (BOS). BOS is primarily classified based on
      airflow obstruction however there is recent data to suggest that the rejection
      process can lead to a restrictive ventilatory defect with involvement of the
      pulmonary vasculature. This study evaluates perfusion heterogeneity in different
      BOS stages by measuring the relative dispersion (RD) of an arterial spin
      labelling MRI blood flow image. Acinar ventilation heterogeneity (Sacin) was
      determined using the Multiple Breath Nitrogen Washout technique. In 24 post
      transplant patients with a range of severity in BOS status, Sacin increased as
      BOS level rose from stage 0 to stage 3. In contrast, RD-perfusion was not
      elevated at BOS 1 and 2 combined compared to BOS 0 and becoming elevated only at
      BOS-3. However, RD-perfusion in BOS-0p was elevated compared to BOS-0, without an
      increase in Sacin. These results suggest that BOS-0p is different in nature from
      other BOS stages. 

PMID- 25981892
TI  - Family history of autoimmune diseases is associated with an increased risk of
      autism in children: A systematic review and meta-analysis.
AB  - BACKGROUND: We conducted a systematic review and meta-analysis to summarize the
      current evidence on the relationship between family history of autoimmune
      diseases (ADs) and risk of autism in children, as current evidence suggests
      inconsistent results. METHODS: We identified relevant studies by searching
      PubMed, EmBase, and Web of Science databases up to Dec 2014. Risk estimates from
      individual studies were pooled using random-effects models. Sub-groups analyses
      were conducted by some study-level factors. Publication bias was assessed by
      funnel plots, Egger's regression test and Begg-Mazumdar test. RESULTS: A total of
      11 articles were included in the meta-analysis, including 3 cohort studies, 6
      case-control studies, and 2 cross-sectional studies. The meta-analysis showed
      that family history of all ADs combined was associated with a 28% (95% CI: 12
      48%) higher risk of autism in children. For some specific ADs, evidence synthesis
      for risk of autism in children showed a statistically significant association
      with family history of hypothyroidism (OR=1.64, 95% CI: 1.07-2.50), type 1
      diabetes (OR=1.49, 95% CI: 1.23-1.81), rheumatoid arthritis (OR=1.51, 95% CI:
      1.19-1.91), and psoriasis (OR=1.59, 95% CI: 1.28-1.97). The results varied in
      some subgroups. CONCLUSION: An overall increased risk of autism in children with
      family history of ADs was identified. More mechanistic studies are needed to
      further explain the association between family history of ADs and increased risk
      of autism in children.

PMID- 25981889
TI  - Current status of fluid biomarkers in mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) affects millions of people annually and is
      difficult to diagnose. Mild injury is insensitive to conventional imaging
      techniques and diagnoses are often made using subjective criteria such as self
      reported symptoms. Many people who sustain a mTBI develop persistent post
      concussive symptoms. Athletes and military personnel are at great risk for repeat
      injury which can result in second impact syndrome or chronic traumatic
      encephalopathy. An objective and quantifiable measure, such as a serum biomarker,
      is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments,
      and would further elucidate mTBI pathophysiology. The majority of TBI biomarker
      research focuses on severe TBI with few studies specific to mild injury. Most
      studies use a hypothesis-driven approach, screening biofluids for markers known
      to be associated with TBI pathophysiology. This approach has yielded limited
      success in identifying markers that can be used clinically, additional candidate
      biomarkers are needed. Innovative and unbiased methods such as proteomics,
      microRNA arrays, urinary screens, autoantibody identification and phage display
      would complement more traditional approaches to aid in the discovery of novel
      mTBI biomarkers. 

PMID- 25981893
TI  - Type 1 diabetes is not associated with an increased prevalence of hepatic
      steatosis.
AB  - AIM: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2
      diabetes. Recently, it has been suggested that NAFLD is also frequently
      associated with Type 1 diabetes and diabetic complications. In this study, we set
      out to determine whether Type 1 diabetes was associated with liver fat content
      measured using magnetic resonance imaging. METHODS: One hundred and twenty-eight
      patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67
      participants without diabetes were included in this study. Hepatic steatosis was
      defined as a liver fat content > 5.5%. RESULTS: People with Type 1 diabetes and
      controls were similar for age and BMI. Liver fat content was significantly higher
      in patients with Type 2 diabetes than in patients with Type 1 diabetes and
      controls. In the control group, nine people (13.4%) had steatosis compared with
      six (4.7%) patients with Type 1 diabetes (P = 0.04). Among patients with Type 2
      diabetes group, 166 (62.8%) had steatosis. In multivariate analysis that included
      patients with Type 1 diabetes and participants without diabetes, steatosis was
      associated only with BMI, whereas age, sex, statin therapy and Type 1 diabetes
      were not. In patients with Type 1 diabetes, there was no correlation between
      liver fat content and estimated glomerular filtration rate or carotid intima
      media thickness. CONCLUSIONS: Our data showed that Type 1 diabetes was not
      associated with an increased prevalence of steatosis. Moreover, our study
      provided no specific arguments concerning a link between liver fat content and
      diabetic complications in patients with Type 1 diabetes.

PMID- 25981895
TI  - Measurement Invariance Across Parent and Self-Ratings of Extremely Low Birth
      Weight Survivors and Normal Birth Weight Controls in Childhood and Adolescence on
      the Child Behavior Checklist and Youth Self-Report.
AB  - OBJECTIVE: This study examined the measurement invariance of the Child Behavior
      Checklist (CBCL) and Youth Self-Report (YSR) DSM-oriented scales between
      extremely low birth weight (ELBW) and normal birth weight (NBW) youth. METHODS: 
      The sample included 158 ELBW survivors and 145 matched, NBW controls at 8 and 12
      16 years of age. RESULTS: Strict invariance was established at 8 years for parent
      reported CBCL attention-deficit hyperactivity, conduct, and oppositional defiant
      scales, though invariance could not be established for affective problems at 8 or
      12-16 years. Strict invariance was observed between 12-16-year-old ELBW and NBW
      groups on attention-deficit hyperactivity, anxiety, and oppositional defiant CBCL
      and YSR scales. Invariance could not be established for youth-reported conduct
      problems. CONCLUSIONS: While the majority of CBCL/YSR DSM-oriented subscales
      assess the same concepts in both ELBW and NBW children and adolescents across
      parent and youth reports, this may not be the case for affective and conduct
      problems.

PMID- 25981894
TI  - Mitochondrial activity in gametes and transmission of viable mtDNA.
AB  - BACKGROUND: The retention of a genome in mitochondria (mtDNA) has several
      consequences, among which the problem of ensuring a faithful transmission of its
      genetic information through generations despite the accumulation of oxidative
      damage by reactive oxygen species (ROS) predicted by the free radical theory of
      ageing. A division of labour between male and female germ line mitochondria was
      proposed: since mtDNA is maternally inherited, female gametes would prevent
      damages by repressing oxidative phosphorylation, thus being quiescent genetic
      templates. We assessed mitochondrial activity in gametes of an unusual biological
      system (doubly uniparental inheritance of mitochondria, DUI), in which also sperm
      mtDNA is transmitted to the progeny, thus having to overcome the problem of
      maintaining genetic information viability while producing ATP for swimming.
      RESULTS: Ultrastructural analysis shows no difference in the conformation of
      mitochondrial cristae in male and female mature gametes, while mitochondria in
      immature oocytes exhibit a simpler internal structure. Our data on
      transcriptional activity in germ line mitochondria show variability between sexes
      and different developmental stages, but we do not find evidence for
      transcriptional quiescence of mitochondria. Our observations on mitochondrial
      membrane potential are consistent with mitochondria being active in both male and
      female gametes. CONCLUSIONS: Our findings and the literature we discussed may be
      consistent with the hypothesis that template mitochondria are not functionally
      silenced, on the contrary their activity might be fundamental for the inheritance
      mechanism. We think that during gametogenesis, fertilization and embryo
      development, mitochondria undergo selection for different traits (e.g.
      replication, membrane potential), increasing the probability of the transmission
      of functional organelles. In these phases of life cycle, the great reduction in
      mtDNA copy number per organelle/cell and the stochastic segregation of mtDNA
      variants would greatly improve the efficiency of selection. When a higher mtDNA
      copy number per organelle/cell is present, selection on mtDNA deleterious mutants
      is less effective, due to the buffering effect of wild-type variants. In our
      opinion, a combination of drift and selection on germ line mtDNA population,
      might be responsible for the maintenance of viable mitochondrial genetic
      information through generations, and a mitochondrial activity would be necessary
      for the selective process.

PMID- 25981896
TI  - Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as
      primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk
      breast cancer: results of the phase II CAPRICE study.
AB  - Anthracycline and taxane-based primary chemotherapy (PCT) is the standard
      treatment for high-risk breast cancer (HRBC). However, conventional
      anthracyclines are not commonly used in elderly patients or those prone to
      cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy,
      but less cardiotoxicity than conventional anthracyclines. We conducted a phase II
      single-arm trial to assess the efficacy and safety of PCT based on PLD followed
      by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients
      with stage II-IIIB breast cancer and at least one risk factor for developing
      cardiotoxicity initiated PLD 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 4
      weeks for four cycles, followed by 80 mg/m(2) weekly PTX for 12. Close cardiac
      monitoring was performed. Primary endpoint was the pathological complete response
      rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty
      four per cent of patients were older than 65 years, 64 % suffered from
      hypertension, and 10 % had prior cardiac disease. In an intention-to-treat
      analysis, breast pCR was 32 % (95 % CI 19.5-46.7 %) and pCR in breast and axilla
      was 24 % (95 % CI 12.1-35.8 %). At diagnosis only, 26 % of patients were
      candidates for breast conservative surgery, which increased to 58.7 % after PCT.
      No significant decrease in left ventricular ejection fraction was seen. PLD
      followed by PTX was feasible in a fragile population of patients who were not
      candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to
      standard therapy and could therefore be an option for elderly patients or
      cardiotoxicity-prone who present HRBC. 

PMID- 25981897
TI  - Determining issues of importance for the evaluation of quality of life and
      patient-reported outcomes in breast cancer: results of a survey of 1072 patients.
AB  - Identifying key issues for patients is central to assessing treatment for cancer,
      especially when evaluating health-related quality of life (QL) and patient
      reported outcomes (PROs). This study was conducted to provide enhanced content
      validity support by incorporating the views of a large number of patients with
      breast cancer. This methodological study used an anonymous, cross-sectional,
      electronic web-based survey of 1072 patients with a diagnosis of breast cancer.
      Patients ranked the importance of 21 issues on a 5-point scale. Issues included
      general, physical, functional, psychosocial, and summative items. Analysis was
      also performed by four key factors (age group, time since diagnosis, adjuvant
      treatment or not, and tumor extent). All of the top five issues rated as either
      "very important" or "important" were global issues-rather than symptoms-such as
      maintaining quality of life (ranked in these two highest categories by 99 % of
      patients), maintaining independence (97 %), and ability to perform normal
      activities (97 %). The abilities to concentrate and to be able to sleep (97 and
      96 %, respectively) were ranked above specific breast cancer symptoms. Specific
      symptoms included within the top ten highest ranked items were fatigue,
      depression, anxiety, shortness of breath, and pain. This is the largest analysis
      of evidence-based data determining support for content validity for QL and PROs
      provided by patients with breast cancer. While symptoms are important to
      patients, the survey also demonstrates that PRO measures that only evaluate
      symptoms are not fully responding to patient-expressed needs. These results
      provide confidence in the content of quality of life measures for large groups of
      patients with breast cancer, including the new Breast Cancer Symptom Scale (BCSS)
      questionnaire. 

PMID- 25981898
TI  - TP53 germline mutation may affect response to anticancer treatments: analysis of
      an intensively treated Li-Fraumeni family.
AB  - Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited disorder
      associated with the occurrence of a wide spectrum of early-onset malignancies,
      the most prevalent being breast cancer and sarcoma. The presence of TP53 germline
      mutations in the majority of LFS patients suggests a genetic basis for the cancer
      predisposition. No special recommendations for the treatment of LFS patients have
      been made to date, except that of minimizing radiation. We hypothesized that TP53
      germline mutations may be associated not only with cancer predisposition, but
      also with lack of response to chemo- and radiotherapy. Here, we present an
      Austrian LFS family whose members were intensively treated with chemo- and
      radiotherapy due to cancers that occurred at a predominantly young age, including
      eight breast cancers in six patients. Material from seven family members was
      screened for p53 mutation by Sanger sequencing and immunohistochemistry. A rare
      missense mutation in the tetramerization domain of exon 10 of the TP53 gene was
      found to segregate with malignant disease in this family. Lack of response to
      various chemotherapies and radiotherapy could be ascertained by histopathology of
      surgical specimens after neoadjuvant treatment, by cancer relapse occurring while
      receiving adjuvant systemic treatment and by the occurrence of second primaries
      in areas of adjuvant radiation. Our observations suggest that current standards
      of cancer treatment may not be valid for patients with LFS. In patients with TP53
      germline mutation, cytotoxic treatment may bear not only the risk of tumor
      induction but also the risk of treatment failure. 

PMID- 25981900
TI  - Status of estrogen receptor 1 (ESR1) gene in mastopathy predicts subsequent
      development of breast cancer.
AB  - Mastopathy is a common disease of the breast likely associated with elevated
      estrogen levels and a putative risk factor for breast cancer. The role of
      estrogen receptor alpha (ESR1) in mastopathy has not been investigated
      previously. Here, we investigated the prevalence of ESR1 gene amplification in
      mastopathy and its prediction for breast cancer. Paraffin-embedded tissues from
      58 women with invasive breast cancer were analyzed. For all women, tissues with
      mastopathy taken at least 1.5 years before first diagnosis of breast cancer were
      available. Tissue from 46 women with mastopathy without a diagnosis of breast
      carcinoma in the observed time frame (12-18 years) was used as control.
      Fluorescence in situ hybridization analysis revealed that ESR1 was amplified in
      nine of 58 (15.5 %) breast cancers. All ESR1-amplified breast cancers were
      strongly positive for estrogen receptor with ER immunohistochemistry.
      Interestingly, in women with ESR1 amplification in breast cancer, the
      amplification was detectable in mastopathic tissues prior to the first diagnosis
      of breast cancer but was absent in tissues from women with mastopathy who did not
      develop breast cancer. Our study suggests that ESR1 gene amplification is an
      early event in breast pathology and might be a helpful predictive marker to
      identify patients at high risk of developing breast cancer. 

PMID- 25981899
TI  - Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT
      trial).
AB  - Chemotherapy-related amenorrhea (CRA) is associated with infertility and
      menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause
      amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA
      in approximately 50 % of all premenopausal recipients [1]. 410 patients enrolled
      on the APT Trial, a single-arm phase 2 adjuvant study of 12 weeks of paclitaxel
      and trastuzumab followed by nine months of trastuzumab monotherapy. Eligible
      patients had <=3 cm node-negative HER2 + breast cancers. Premenopausal enrollees
      were asked to complete menstrual surveys every 3-12 months for 72 months. Women
      who responded to at least one survey at least 15 months after chemotherapy
      initiation (and who did not undergo hysterectomy and/or bilateral oophorectomy or
      receive ovarian suppressing medications prior to 15 months) were included in this
      analysis. A participant was defined as having amenorrhea in follow-up if her self
      reported last menstrual period at last follow-up was greater than 12 months prior
      to the survey. Among the 64 women in the evaluable population (median age at
      study entry 44 years, range 27-52 years), the median time between chemotherapy
      initiation and last menstrual survey was 51 months (range 16-79). 18 of 64 women
      (28 %, 95 % CI 18-41 %) were amenorrheic at that time point. Amenorrhea rates
      among premenopausal women treated with adjuvant paclitaxel and trastuzumab for
      early stage breast cancer appear lower than those seen historically with standard
      alkylator-based breast cancer regimens. Future studies are needed to understand
      the impact of this regimen on related issues of fertility and menopausal
      symptoms. 

PMID- 25981901
TI  - Correlating transcriptional networks with pathological complete response
      following neoadjuvant chemotherapy for breast cancer.
AB  - We aimed to investigate the association between gene co-expression modules and
      responses to neoadjuvant chemotherapy in breast cancer by using a systematic
      biological approach. The gene expression profiles and clinico-pathological data
      of 508 (discovery set) and 740 (validation set) patients with breast cancer who
      received neoadjuvant chemotherapy were analyzed. Weighted gene co-expression
      network analysis was performed and identified seven co-regulated gene modules.
      Each module and gene signature were evaluated with logistic regression models for
      pathological complete response (pCR). The association between modules and pCR in
      each intrinsic molecular subtype was also investigated. Two transcriptional
      modules were correlated with tumor grade, estrogen receptor status, progesterone
      receptor status, and chemotherapy response in breast cancer. One module that
      constitutes upregulated cell proliferation genes was associated with a high
      probability for pCR in the whole (odds ratio (OR) = 5.20 and 3.45 in the
      discovery and validation datasets, respectively), luminal B, and basal-like
      subtypes. The prognostic potentials of novel genes, such as MELK, and pCR-related
      genes, such as ESR1 and TOP2A, were identified. The upregulation of another gene
      co-expression module was associated with weak chemotherapy responses (OR = 0.19
      and 0.33 in the discovery and validation datasets, respectively). The novel gene
      CA12 was identified as a potential prognostic indicator in this module. A systems
      biology network-based approach may facilitate the discovery of biomarkers for
      predicting chemotherapy responses in breast cancer and contribute in developing
      personalized medicines. 

PMID- 25981902
TI  - Loss of PTEN expression is associated with aggressive behavior and poor prognosis
      in Middle Eastern triple-negative breast cancer.
AB  - PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling
      pathway which is involved in the pathogenesis of many different tumor types and
      serves as a prognostic marker in breast cancer. However, the significance of the
      role of PTEN in Middle Eastern ethnic breast cancer has not been explored
      especially with the fact that breast cancer originating from this ethnic
      population tend to behave more aggressively than breast cancer in the west. In
      this study, we analyzed PTEN alteration in a tissue microarray format containing
      more than 1000 primary breast cancers with clinical follow-up data. Tissue
      Microarray sections were analyzed for protein expression and copy number change
      using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN
      immunostaining was observed in 77 % of the cases. PTEN loss was significantly
      associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor
      recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN
      loss in triple-negative breast cancers was significantly associated with rapid
      tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN
      deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression
      occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may
      potentially lead to an aggressive behavior of tumor cells through stimulation of
      tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as
      potential therapeutic target in triple-negative breast cancers since loss of its
      expression is shown to be significantly associated with this aggressive subtype
      of breast cancer. 

PMID- 25981903
TI  - A multi-organisation aged care emergency service for acute care management of
      older residents in aged care facilities.
AB  - This case study describes a multi-organisation aged care emergency (ACE) service.
      The service was designed to enable point-of-care assessment and management for
      older people in residential aged care facilities (RACFs). Design of the ACE
      service involved consultation and engagement of multiple key stakeholders. The
      ACE service was implemented in a large geographical region of a single Medicare
      Local (ML) in New South Wales, Australia. The service was developed over several
      phases. A case control pilot evaluation of one emergency department (ED) and four
      RACFs revealed a 16% reduction in presentations to the ED as well as reductions
      in admission to the hospital following ED presentation. Following initial pilot
      work, the ACE service transitioned across another five EDs and 85 RACFs in the
      local health district. The service has now been implemented in a further 10 sites
      (six metropolitan and four rural EDs) across New South Wales. Ongoing evaluation
      of the implementation continues to show positive outcomes. The ACE service offers
      a model shown to reduce ED presentations and admissions from RACFs, and provide
      quality care with a focus on the needs of the older person.

PMID- 25981904
TI  - Drug-induced movement disorders.
AB  - INTRODUCTION: Drug-induced movement disorders (DIMDs) can be elicited by several
      kinds of pharmaceutical agents. The major groups of offending drugs include
      antidepressants, antipsychotics, antiepileptics, antimicrobials, antiarrhythmics,
      mood stabilisers and gastrointestinal drugs among others. AREAS COVERED: This
      paper reviews literature covering each movement disorder induced by commercially
      available pharmaceuticals. Considering the magnitude of the topic, only the most
      prominent examples of offending agents were reported in each paragraph paying a
      special attention to the brief description of the pathomechanism and therapeutic
      options if available. EXPERT OPINION: As the treatment of some DIMDs is quite
      challenging, a preventive approach is preferable. Accordingly, the use of the
      offending agents should be strictly limited to appropriate indications and they
      should be applied in as low doses and as short duration as the patient's
      condition allows. As most of DIMDs are related to an unspecific adverse action of
      medications in the basal ganglia and the cerebellum, future research should focus
      on better characterisation of the neurochemical profile of the affected
      functional systems, in addition to the development of drugs with higher
      selectivity and better side-effect profile.

PMID- 25981906
TI  - DNA Labeling Generates a Unique Amplification Probe for Sensitive
      Photoelectrochemical Immunoassay of HIV-1 p24 Antigen.
AB  - Photoelectrochemical (PEC) immunoassay is an attractive methodology as it allows
      for an elegant and sensitive protein assay. However, advanced PEC immunoassay
      remains challenging and the established amplifications rely almost exclusively on
      the labeling of various enzymes, which usually suffer the inferior stabilities.
      Here we report the development and validation of the DNA labeling that leads to a
      unique amplification probe for the sensitive PEC immunoassay of HIV-1 capsid
      protein, p24 antigen, an important biomarker of human immune deficiency virus
      (HIV). Following the sandwich immunobinding, the DNA tags could be released and
      the subsequent dipurinization of the oligonucleotide strands enables the easy
      oxidation of free nucleobases at a CdTe quantum dots (QDs) modified ITO
      transducer. Such DNA tags induced PEC amplification and readout permits the
      exquisite assay of HIV-1 p24 antigen with high sensitivity. As compared to the
      existing method of enzymatic labeling, the easy preparation and stability of
      these labels make them very suitable for PEC amplification. Another merit of this
      method is that it separates the immunobinding from the PEC transducer, which
      eliminates the commonly existing affection during the biorecognition processes.
      This work paves a new route for the PEC immunoassay of HIV-1 p24 antigen and
      provides a general format for the PEC biomolecular detection by means of the DNA
      labeling. 

PMID- 25981907
TI  - UV-A and UV-C light induced hydrophilization of dental implants.
AB  - OBJECTIVES: Wettability is increasingly considered to be an important factor
      determining biological responses to implant materials. In this context, the
      purpose of this study was to compare the dynamic wettability of dental implants
      made from different bulk materials and modified by different surface
      modifications, and to analyze the respective changes of wettability upon
      irradiating these implants by UV-A or UV-C light. METHODS: Four original screw
      type implants were investigated: One grit-blasted/acid-etched and one anodically
      oxidized titanium, one zirconia and one polyetheretherketone implant.
      Additionally, experimental, screwless, machined titanium cylinders were included
      in the study. Part of that cylinders and of blasted/etched implants were further
      modified by a magnetron-sputtered photocatalytic anatase thin film. Scanning
      electron microscopy was used to investigate the surface micro- and
      nanostructures. Samples were treated by UV-A (382nm, 25mWcm(-2)) and UV-C (260nm,
      15mWcm(-2)) for entire 40min, respectively, and their wettability was quantified
      by dynamic contact angle (CA) analysis from multi-loop Wilhelmy experiments.
      RESULTS: All implants are characterized by submicron- and nanosized surface
      features. Unexposed implants were hydrophobic (CA>90 degrees ). Upon UV-A, solely
      the implants with anatase coating became superhydrophilic (CA<5 degrees ). Upon
      UV-C, the blasted/etched implants turned superhydrophilic, the anodized titanium
      and the zirconia implants were considerably (CA=34 degrees  and 27 degrees ,
      respectively) and the PEEK implants slightly (CA=79 degrees ) hydrophilized.
      SIGNIFICANCE: The wettability of implant surfaces can be improved by UV
      irradiation. The efficiency of UV-A and UV-C irradiation to lower the CA by
      photocatalysis or photolysis, however, is strongly dependent on the specific
      material and surface. Thus, attempts to photofunctionalize these surfaces by
      irradiation is expected to result in a different pattern of bioresponses.

PMID- 25981909
TI  - Characteristics and Fate of Systemic Artery Aneurysm after Kawasaki Disease.
AB  - OBJECTIVE: To determine the long-term outcome of systemic artery aneurysms (SAAs)
      after Kawasaki disease (KD). STUDY DESIGN: We investigated the characteristics
      and the fate of SAAs in 20 patients using medical records and angiograms. The age
      of onset of KD ranged from 1 month to 20 months. The interval from the onset of
      KD to the latest angiogram ranged from 16 months to 24 years. The regression rate
      of peripheral artery aneurysm and the frequency of stenotic lesions were analyzed
      by the Kaplan-Meier method in 11 patients who had undergone initial angiography
      within 4 months. RESULTS: The mean duration of fever was 24 +/- 12 days. All 20
      patients had at least 1 symmetric pair of aneurysms in bilateral peripheral
      arteries, and 16 patients had multiple SAAs. The distributions of SAAs was as
      follows: brachial artery, 30; common iliac artery, 20; internal iliac artery, 21;
      abdominal aortic aneurysm, 7; and others, 29. The frequencies of regression of
      SAA and of the occurrence of stenotic lesions at 20 years after the onset of KD
      were 51% and 25%, respectively (n = 42). The diameter of all SAAs in the acute
      phase leading to stenotic lesions in the late period was >10 mm. CONCLUSION: SAAs
      occurred symmetrically and were multiple in younger infants and those with severe
      acute vasculitis. The fate of SAAs resembles that of coronary artery aneurysms,
      and depends on the diameter during the acute phase. Larger SAAs can lead to
      stenotic lesions in the late period.

PMID- 25981908
TI  - High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.
AB  - BACKGROUND: Whether noninvasive ventilation should be administered in patients
      with acute hypoxemic respiratory failure is debated. Therapy with high-flow
      oxygen through a nasal cannula may offer an alternative in patients with
      hypoxemia. METHODS: We performed a multicenter, open-label trial in which we
      randomly assigned patients without hypercapnia who had acute hypoxemic
      respiratory failure and a ratio of the partial pressure of arterial oxygen to the
      fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy,
      standard oxygen therapy delivered through a face mask, or noninvasive positive
      pressure ventilation. The primary outcome was the proportion of patients
      intubated at day 28; secondary outcomes included all-cause mortality in the
      intensive care unit and at 90 days and the number of ventilator-free days at day
      28. RESULTS: A total of 310 patients were included in the analyses. The
      intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow
      oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the
      noninvasive-ventilation group (P=0.18 for all comparisons). The number of
      ventilator-free days at day 28 was significantly higher in the high-flow-oxygen
      group (24+/-8 days, vs. 22+/-10 in the standard-oxygen group and 19+/-12 in the
      noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for
      death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with
      standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78)
      with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS: In
      patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with
      high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in
      significantly different intubation rates. There was a significant difference in
      favor of high-flow oxygen in 90-day mortality. (Funded by the Programme
      Hospitalier de Recherche Clinique Interregional 2010 of the French Ministry of
      Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

PMID- 25981910
TI  - Representation of particle motion in the auditory midbrain of a developing
      anuran.
AB  - In bullfrog tadpoles, a "deaf period" of lessened responsiveness to the pressure
      component of sounds, evident during the end of the late larval period, has been
      identified in the auditory midbrain. But coding of underwater particle motion in
      the vestibular medulla remains stable over all of larval development, with no
      evidence of a "deaf period." Neural coding of particle motion in the auditory
      midbrain was assessed to determine if a "deaf period" for this mode of
      stimulation exists in this brain area in spite of its absence from the vestibular
      medulla. Recording sites throughout the developing laminar and medial principal
      nuclei show relatively stable thresholds to z-axis particle motion, up until the
      "deaf period." Thresholds then begin to increase from this point up through the
      rest of metamorphic climax, and significantly fewer responsive sites can be
      located. The representation of particle motion in the auditory midbrain is less
      robust during later compared to earlier larval stages, overlapping with but also
      extending beyond the restricted "deaf period" for pressure stimulation. The
      decreased functional representation of particle motion in the auditory midbrain
      throughout metamorphic climax may reflect ongoing neural reorganization required
      to mediate the transition from underwater to amphibious life. 

PMID- 25981913
TI  - Self-Assembling Peptides Form Immune Suppressive Amyloid Fibrils Effective in
      Autoimmune Encephalomyelitis.
AB  - Amyloidogenic proteins have long been linked to neurodegenerative diseases.
      However, amyloid fibrils composed of six amino acids are protective in an animal
      model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis
      (EAE). The reduction of pro-inflammatory cytokines, decrease in the number of
      inflammatory foci in the parenchyma and meninges of the brain and spinal cord,
      and amelioration of the neurological signs of EAE when amyloid fibril-forming
      hexapeptides are administered reveal that some fibrils provide benefit. The
      therapeutic activity of the amyloid fibrils arise from diverse pathways that
      include binding of pro-inflammatory mediators in the plasma, reduction of IL-6,
      TNF-alpha, and IFN-gamma levels, and induction of type 1 interferon (IFN). Type 1
      IFN has been used widely as a therapeutic agent for the treatment of MS and has
      been shown to be therapeutic in EAE with adoptive transfer of Th1 lymphocytes.
      However, type 1 IFN is known to exacerbate EAE with adoptive transfer of Th17
      lymphocytes. Indeed, the amyloid fibril-forming peptide Tau 623-628 was
      therapeutic in Th1 adoptively transferred EAE, but ineffective in Th17 adoptively
      transferred EAE. However, the therapeutic effect of Tau 623-628 was restored in
      IFN-alpha/beta receptor (IFNAR) knockout mice, indicating that other immune
      pathways independent of type 1 IFN induction play a role in the amelioration of
      EAE. Moreover, Amylin 28-33, a polar, non-ionizable peptide that does not form
      fibrils as rapidly as Tau 623-628, induces a small fraction of type 1 IFN
      compared to Tau 623-628 and is therapeutic in Th17 EAE. The diverse immunological
      pathways modulated by the self-assembling hexapeptides are under investigation
      with a goal to develop novel, safe, and potent therapeutics for
      neuroinflammation. 

PMID- 25981911
TI  - Identification and characterisation of putative seminal fluid proteins from male
      reproductive tissue EST libraries in tiger beetles.
AB  - BACKGROUND: The study of proteins transferred through semen can provide important
      information for biological questions such as adaptive evolution, the origin of
      new species and species richness. The objective of this study was to identify
      seminal fluid proteins (SFPs) that may contribute to the study of the
      reproductive system of tiger beetles (cicindelids), a group of more than 2,500
      species distributed worldwide that occupy a great diversity of habitats. RESULTS:
      Two cDNA libraries were constructed from the male gonads of Calomera littoralis
      and Cephalota litorea. Expressed sequence tags (ESTs) were analysed by
      bioinformatics approaches and 14 unigenes were selected as candidate SFPs, which
      were submitted to Reverse Transcription Polymerase Chain Reaction (RT-PCR) to
      identify patterns of tissue-specific expression. We have identified four novel
      putative SFPs of cicindelids, of which similarity searches did not show
      homologues with known function. However, two of the protein classes (immune
      response and hormone) predicted by Protfun are similar to SFPs reported in other
      insects. Searches for homology in other cicindelids showed one lineage specific
      SFPs (rapidly evolving proteins), only present in the closely related species C.
      littoralis and Lophyra flexuosa and two conserved SFP present in other tiger
      beetles species tested. CONCLUSIONS: This work represents the first
      characterisation of putative SFPs in Adephagan species of the order Coleoptera.
      The results will serve as a foundation for further studies aimed to understand
      gene (and protein) functions and their evolutionary implications in this group of
      ecologically relevant beetles.

PMID- 25981912
TI  - The Computational Complexity of Valuation and Motivational Forces in Decision
      Making Processes.
AB  - The concept of value is fundamental to most theories of motivation and decision
      making. However, value has to be measured experimentally. Different methods of
      measuring value produce incompatible valuation hierarchies. Taking the agent's
      perspective (rather than the experimenter's), we interpret the different
      valuation measurement methods as accessing different decision-making systems and
      show how these different systems depend on different information processing
      algorithms. This identifies the translation from these multiple decision-making
      systems into a single action taken by a given agent as one of the most important
      open questions in decision making today. We conclude by looking at how these
      different valuation measures accessing different decision-making systems can be
      used to understand and treat decision dysfunction such as in addiction. 

PMID- 25981916
TI  - Are we developing walkable suburbs through urban planning policy? Identifying the
      mix of design requirements to optimise walking outcomes from the 'Liveable
      Neighbourhoods' planning policy in Perth, Western Australia.
AB  - BACKGROUND: Planning policy makers and practitioners are requesting clearer
      guidance on the 'essential' ingredients as assessed by public health researchers
      to ensure suburban neighbourhood environments are designed to promote active
      living behaviours such as walking. OBJECTIVES: To identify the combination of
      design requirements from the 'Liveable Neighbourhoods' (LN) planning policy in
      Perth, Western Australia that were optimally supportive of walking. METHODS: K
      means cluster analysis identified groups of developments with homogeneous LN
      features from its community design (CD), movement network (MN), lot layout (LL)
      and public parkland (PP) elements. Walking behaviours measured using the
      Neighbourhood Physical Activity Questionnaire were compared between participants
      resident in the different clusters, adjusting for demographic characteristics,
      self-selection factors, stage of construction and scale of development. RESULTS:
      Compared with participants living in the referent cluster of 'poor CD and PP
      developments' those living in: 'MN and LL developments' had higher odds of doing
      any (OR = 1.74; 95 % CI = 1.22, 2.48) and >=60 min walking for recreation (WR)
      (OR = 2.05; 1.46, 2.88); 'PP developments' had increased odds of doing any WR (OR
      = 3.53; 2.02, 6.17), >=60 min WR (OR = 3.37; 1.98, 5.74) and any total walking
      (TW) (OR = 2.35; 1.36, 4.09); 'CD-MN developments' had increased odds of doing
      any walking for transport (WT) (OR = 2.64; 1.38, 5.06), >=60 min WT (OR = 1.98;
      1.09, 3.61), any TW (OR = 1.71; 1.44, 2.03), >=60 min TW (OR = 1.77; 1.14, 2.76)
      and >=150 min TW (OR = 1.47; 1.15, 1.86). CONCLUSIONS: This study is the first to
      have empirically identified a mix of specific and distinguishing planning policy
      neighbourhood design requirements to optimise walking outcomes. These findings
      will assist in the assessment of urban plans for greenfield suburban developments
      designed to promote walking and physical activity.

PMID- 25981914
TI  - Ultrashort echo time magnetization transfer (UTE-MT) imaging of cortical bone.
AB  - Magnetization transfer (MT) imaging is one way to indirectly assess pools of
      protons with fast transverse relaxation. However, conventional MT imaging
      sequences are not applicable to short T2 tissues such as cortical bone.
      Ultrashort echo time (UTE) sequences with TE values as low as 8 us can detect
      signals from different water components in cortical bone. In this study we aim to
      evaluate two-dimensional UTE-MT imaging of cortical bone and its application in
      assessing cortical bone porosity as measured by micro-computed tomography (MUCT)
      and biomechanical properties. In total, 38 human cadaveric distal femur and
      proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical
      bone for quantitative UTE-MT MR imaging, MUCT, and biomechanical testing. Off
      resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets
      (Deltaf) were calculated and compared with porosity assessed with MUCT, as well
      as elastic (modulus, yield stress, and strain) and failure (ultimate stress,
      failure strain, and energy) properties, using Pearson correlation and linear
      regression. A moderately strong negative correlation was observed between OSR and
      MUCT porosity (R(2)  = 0.46-0.51), while a moderate positive correlation was
      observed between OSR and yield stress (R(2)  = 0.25-0.30) and failure stress
      (R(2)  = 0.31-0.35), and a weak positive correlation (R(2)  = 0.09-0.12) between
      OSR and Young's modulus at all off-resonance saturation frequencies. OSR
      determined with the UTE-MT sequence provides quantitative information on cortical
      bone and is sensitive to MUCT porosity and biomechanical function.

PMID- 25981917
TI  - Differential proteomic analysis on the effects of 2-methoxy-1,4-naphthoquinone
      towards MDA-MB-231 cell line.
AB  - BACKGROUND: We have previously reported the anti-metastatic effects of 2-methoxy
      1,4-naphthoquinone (MNQ) against MDA-MB-231 cell line. PURPOSE: To investigate
      the molecular mechanism underlying the anti-metastatic effects of MNQ towards MDA
      MB-231 cell line via the comparative proteomic approach. STUDY DESIGN/METHODS:
      Differentially expressed proteins in MNQ-treated MDA-MB-231 cells were identified
      by using two-dimensional gel electrophoresis coupled with tandem mass
      spectrometry. Proteins and signalling pathways associated with the identified MNQ
      altered proteins were studied by using Western blotting. RESULTS: Significant
      modulation of MDA-MB-231 cell proteome was observed upon treatment with MNQ in
      which the expressions of 19 proteins were found to be downregulated whereas
      another eight were upregulated (>1.5 fold, p < 0.05). The altered proteins were
      mainly related to cytoskeletal functions and regulations, mRNA processing,
      protein modifications and oxidative stress response. Notably, two of the
      downregulated proteins, protein S100-A4 (S100A4) and laminin-binding protein
      (RPSA) are known to play key roles in driving metastasis and were verified using
      Western blotting. Further investigation using Western blotting also revealed that
      MNQ decreased the activations of pro-metastatic ERK1/2 and NF-kappaB signalling
      pathways. Moreover, MNQ was shown to stimulate the expression of the metastatic
      suppressor, E-cadherin. CONCLUSION: This study reports a proposed mechanism by
      which MNQ exerts its anti-metastatic effects against MDA-MB-231 cell line. The
      findings from this study offer new insights on the potential of MNQ to be
      developed as a novel anti-metastatic agent.

PMID- 25981918
TI  - Protective effect of Wuzhi tablet (Schisandra sphenanthera extract) against
      cisplatin-induced nephrotoxicity via Nrf2-mediated defense response.
AB  - Cisplatin is a potent anti-cancer agent for various types of tumors. However, the
      clinical use of cisplatin is often limited by its nephrotoxicity. This study
      reports that WZ tablet (WZ, a preparation of an ethanol extract of Schisandra
      sphenanthera) mitigates cisplatin-induced toxicity in renal epithelial HK-2 cells
      and in mice. Pretreatment of HK-2 cells with WZ ameliorated cisplatin-induced
      cytotoxicity caused by oxidative stress, as was demonstrated by reductions in the
      levels of reactive oxygen species (ROS) and increased levels of glutathione
      (GSH). WZ facilitated the nuclear accumulation of the transcription factor NF-E2
      related factor 2 (Nrf2) and the subsequent expression of its target genes such as
      NAD(P)H: quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and glutamate
      cysteine ligase (GCL). Protective effects of WZ on cisplatin-induced
      nephrotoxicity were also observed in mice. WZ attenuated cisplatin-induced renal
      dysfunction, structural damage and oxidative stress. The nuclear accumulation of
      Nrf2 and its target genes were increased by WZ treatment. Taken together, these
      findings demonstrated WZ have a protective effect against cisplatin-induced
      nephrotoxicity by activation of the Nrf2 mediated defense response, which is of
      significant importance for therapeutic intervention in cisplatin induced renal
      injury.

PMID- 25981919
TI  - Sensitivity of apoptosis-resistant colon cancer cells to tanshinones is mediated
      by autophagic cell death and p53-independent cytotoxicity.
AB  - BACKGROUND: Multidrug resistance (MDR) develops in nearly all patients with colon
      cancer. The reversal of MDR plays an important role in the success of colon
      cancer chemotherapy. One of the commonest mechanisms conferring MDR is the
      suppression of apoptosis in cancer cells. PURPOSE: This study investigated the
      sensitivity of cryptotanshinone (CTS) and dihydrotanshinone (DTS), two lipophilic
      tanshinones from a traditional Chinese medicine Salvia miltiorrhiza, in apoptosis
      resistant colon cancer cells. METHODS: Cell viability was measured by MTT assay.
      Cell cycle distribution and apoptosis were determined by flow cytometry. Protein
      levels were analyzed by western blot analysis. The formation of acidic vesicular
      organelles was visualized by acridine orange staining. RESULTS: Experimental
      results showed that multidrug-resistant colon cancer cells SW620 Ad300 were
      sensitive to both CTS and DTS in terms of cell death, but with less induction of
      apoptosis when compared with the parental cells SW620, suggesting that other
      types of cell death such as autophagy could occur. Indeed, the two tanshinones
      induced more LC3B-II accumulation in SW620 Ad300 cells with increased autophagic
      flux. More importantly, cell viability was increased after autophagy inhibition,
      indicating that autophagy induced by the two tanshinones was pro-cell death.
      Besides, the cytotoxic actions of the two tanshinones were p53-independent, which
      could be useful in inhibiting the growth of apoptosis-resistant cancer cells with
      p53 defects. CONCLUSION: The current findings strongly indicate that both CTS and
      DTS could inhibit the growth of apoptosis-resistant colon cancer cells through
      induction of autophagic cell death and p53-independent cytotoxicity. They are
      promising candidates to be further developed as therapeutic agents in the
      adjuvant therapy for colon cancer, especially for the apoptosis-resistant cancer
      types.

PMID- 25981920
TI  - Capillin, a major constituent of Artemisia capillaris Thunb. flower essential
      oil, induces apoptosis through the mitochondrial pathway in human leukemia HL-60
      cells.
AB  - BACKGROUND: Natural products are one of the most important sources of drugs used
      in pharmaceutical therapeutics. Screening of several natural products in the
      search for novel anticancer agents against human leukemia HL-60 cells led us to
      identify potent apoptosis-inducing activity in the essential oil fraction from
      Artemisia capillaris Thunb. flower. METHODS: The cytotoxic effects of extracts
      were assessed on human leukemia HL-60 cells by XTT assay. Induction of apoptosis
      was assessed by analysis of DNA fragmentation and nuclear morphological change.
      The plant name was checked with the plant list website
      (http://www.theplantlist.org). RESULTS: A purified compound from the essential
      oil fraction from Artemisia capillaris Thunb. flower that potently inhibited cell
      growth in human leukemia HL-60 cells was identified as capillin. The cytotoxic
      effect of capillin in cells was associated with apoptosis. When HL-60 cells were
      treated with 10(-6) M capillin for 6 h, characteristic features of apoptosis such
      as DNA fragmentation and nuclear fragmentation were observed. Moreover,
      activation of c-Jun N-terminal kinase (JNK) was detected after treatment with
      capillin preceding the appearance of characteristic properties of apoptosis.
      Release of cytochrome c from mitochondria was also observed in HL-60 cells that
      had been treated with capillin. CONCLUSION: Capillin induces apoptosis in HL-60
      cells via the mitochondrial apoptotic pathway, which might be controlled through
      JNK signaling. Our results indicate that capillin may be a potentially useful
      anticancer drug that could enhance therapeutic efficacy.

PMID- 25981921
TI  - Comparative studies of polydatin and resveratrol on mutual transformation and
      antioxidative effect in vivo.
AB  - BACKGROUND: Polydatin and resveratrol are extractives of radix or rhizoma of
      Polygonum cuspidatum, and as the glycoside forms, it is a natural precursor of
      resveratrol. PURPOSE: In this study, we aimed to explore the mutual
      transformation between polydatin and resveratrol in rats, and to compare the
      antioxidative effect of them in vivo. STUDY DESIGN: In this study, we analyzed
      the serum molar concentration of polydatin and resveratrol after oral
      administration in rats and evaluated the anti-oxidative stress effects of them
      using a mouse model. METHODS: Rats were orally administered polydatin or
      resveratrol and the concentration of them in serum were analyzed by high
      performance liquid chromatography (HPLC). Their antioxidative effect was compared
      in mice with oxidative stress cardiomyopathy induced by doxorubicin (DOX).
      RESULTS: The results showed that polydatin and resveratrol could mutually
      transform in vivo, the molar concentration of polydatin in serum was always
      averagely 3.35 and 4.28 times as much as resveratrol after oral administration of
      polydatin and resveratrol at 200 mg/kg, respectively. Both polydatin and
      resveratrol could significantly decrease the content of malonydialdehyde (MDA),
      promote the activities of total superoxide dismutase (T-SOD), catalase (CAT) and
      glutathione peroxidase (GSH-Px) in plasma, and increase the content of
      glutathione (GSH) in myocardial tissue. The effect of polydatin surpassed
      resveratrol, particularly embodied in increasing the activities of T-SOD and CAT,
      and the content of GSH. CONCLUSION: It illustrates that polydatin is the main
      substance in serum after intragastric administration with polydatin or
      resveratrol, and the mutual transformation between polydatin and resveratrol
      keeps balance; they both have the ability of antioxidative stress in vivo, and
      polydatin has a better effect than resveratrol, which hints that polydatin may be
      a substitute for resveratrol in antioxidant for clinical use.

PMID- 25981922
TI  - Marsdenia tenacissima extract enhances gefitinib efficacy in non-small cell lung
      cancer xenografts.
AB  - PURPOSE: The stem of Marsdenia tenacissima (Roxb.) Wight et Arn. has long been
      used as a medicine to treat cancer in China. Our previous in vitro results showed
      that Marsdenia tenacissima extract (MTE) overcomes gefitinib resistance in non
      small cell lung cancer (NSCLC) cells. However, it is unknown whether MTE could
      enhance gefitinib efficacy in vivo. The present study was intended to investigate
      the in vivo anti-tumour activity of MTE combined with gefitinib. METHODS: Human
      NSCLC H460 (K-ras mutation) or H1975 cells (EGFR T790M mutation) were
      subcutaneously inoculated into nude mice. Tumour volume and body weight were
      measured regularly. Resected tumours were weighed after the animals were
      sacrificed. Immunoblotting or immunohistochemistry was used to assess the
      cellular proliferation and apoptosis in xenograft tumour tissue. Expression of
      the EGFR downstream pathways and c-Met were measured with western blot analysis
      to explore possible mechanisms. RESULTS: MTE (5, 10, 20 g/kg) dose-dependently
      reduced tumour growth and induced cell apoptosis. MTE suppressed EGFR related
      signals, and 20 g/kg was the most effective dose. Low-dose MTE (5 g/kg)
      significantly enhanced gefitinib efficacy in resistant H460 and H1975 xenografts.
      The combination inhibited tumour proliferation and induced cell apoptosis in both
      resistant NSCLC xenografts. Constitutive activation of the PI3K/Akt and MEK/ERK
      pathways is related to EGFR-TKI resistance. Accordingly, phosphorylation of
      PI3K/Akt/mTOR and ERK1/2 was suppressed after combination treatment.
      Simultaneously, cross-talked c-Met and EGFR were also prominently lowered in the
      presence of MTE combined with gefitinib. CONCLUSION: The present results suggest
      that the combination of MTE and gefitinib may be a promising therapeutic approach
      to enhance gefitinib efficacy in resistant NSCLC.

PMID- 25981923
TI  - Dioscin and methylprotodioscin isolated from the root of Asparagus
      cochinchinensis suppressed the gene expression and production of airway MUC5AC
      mucin induced by phorbol ester and growth factor.
AB  - BACKGROUND: The root of Asparagus cochinchinensis (Lour.) Merr. has been utilized
      as mucoregulators and expectorants for controlling the airway inflammatory
      diseases in folk medicine. HYPOTHESIS/PURPOSE: We investigated whether dioscin
      and methylprotodioscin isolated from the root of Asparagus cochinchinensis
      (Lour.) Merr. suppress the gene expression and production of airway MUC5AC mucin
      induced by phorbol ester and growth factor. STUDY DESIGN: Confluent NCI-H292
      cells were pretreated with dioscin or methylprotodioscin for 30 min and then
      stimulated with EGF or PMA for 24 h. The MUC5AC mucin gene expression was
      measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA.
      RESULTS: (1) Dioscin and methylprotodioscin suppressed the expression of MUC5AC
      mucin gene induced by EGF or PMA; (2) dioscin suppressed the production of MUC5AC
      mucin induced by either EGF at 10(-5) M (p < 0.05) and 10(-6) M (p < 0.05) or PMA
      at 10(-4) M (p < 0.05), 10(-5) M (p < 0.05) and 10(-6) M (p < 0.05); (3)
      methylprotodioscin also suppressed the production of MUC5AC mucin induced by
      either EGF at 10(-4) M (p < 0.05) or PMA at 10(-4) M (p < 0.05). CONCLUSION:
      These results suggest that dioscin and methylprotodioscin isolated from the root
      of Asparagus cochinchinensis suppress the gene expression and production of
      MUC5AC mucin, by directly acting on airway epithelial cells, and the results are
      consistent with the traditional use of Asparagus cochinchinensis as remedy for
      diverse inflammatory pulmonary diseases.

PMID- 25981924
TI  - Pharmacokinetic synergy from the taxane extract of Taxus chinensis improves the
      bioavailability of paclitaxel.
AB  - BACKGROUND: Taxus chinensis (Pilger) Rehd is widely distributed in China and the
      northern hemisphere, and the most popular medicinal component isolated from Taxus
      chinensis is paclitaxel (PTX), which has now become the first-line
      chemotherapeutic drug for breast cancer and ovarian cancer. Oral administration
      of pure PTX as a potential anti-cancer agent is compromised by low
      bioavailability. HYPOTHESIS/PURPOSE: In the clinical practice of traditional
      Chinese medicine, drug co-administration in the form of mixtures or formula could
      achieve pharmacokinetic/pharmacodynamic synergies. In this study, we aimed to
      investigate whether there exist any 'inherent' phytochemical synergy from Taxus
      chinensis extract that could improve PTX bioavailability. STUDY DESIGN:
      Pharmacokinetic study of PTX after oral administration of Taxus chinensis
      extracts or single PTX was performed. In addition, comparative cytotoxic studies
      were carried out on the MCF-7 breast cancer cell lines. METHODS: The plasma
      concentrations of PTX were determined using a validated high performance
      chromatography tandem mass spectrometry method. The cytotoxicity was compared
      using the MTT assay. RESULTS: Oral administration of taxane fractions isolated
      from Taxus chinensis (containing 17.2% PTX) could achieve remarkably higher blood
      concentration and systemic exposure of PTX in rats, while the retention of PTX
      was significantly improved. Further tissue distribution analysis revealed that
      the penetration of PTX into major tissues was drastically increased compared with
      that of single PTX. In addition, in MCF-7 cells, the co-existing components in
      taxane mixtures could strengthen the inhibitory effects of PTX on tumor cell
      proliferation. CONCLUSION: Together, these results support that administration of
      PTX in the form of taxane mixtures may become a novel approach to improve the
      poor bioavailability of PTX. Moreover, the inherent synergy from Taxus chinensis
      taxane extracts promises a novel strategy to strengthen PTX efficacy.

PMID- 25981925
TI  - Metabolite identification strategy of non-targeted metabolomics and its
      application for the identification of components in Chinese multicomponent
      medicine Abelmoschus manihot L.
AB  - Identification of multicomponent in traditional Chinese medicine (TCM) is complex
      and time-consuming. The inspection of the full-scan mass chromatograms was
      usually performed manually, which is labor-intensive. It is difficult to
      distinguish low response signals from complex chemical background. Furthermore,
      this process is typically based on earlier knowledge of the chemical composition
      of TCM, and those molecules that have not been characterized earlier were thus
      ignored. In this paper, a strategy using UPLC-MS combined with pattern
      recognition analysis was developed to simplify and quicken the identification of
      multicomponent in Abelmoschus manihot (L.) Medik. First, complex signals obtained
      by UPLC-MS were processed using automated data mining algorithm and further
      processed with multivariate chemometric methods. Multicomponent in Abelmoschus
      manihot L. can be clearly displayed in S- and VIP-plot. Using this method, 320
      peaks which present in Abelmoschus manihot L. were detected. In the next step,
      accurate mass spectra of the characteristic markers acquired by QTOF MS were used
      to estimate their elemental formulae and enable structure identification. By
      searching in METLIN database, 41 components were tentatively identified in
      Abelmoschus manihot L. Our results showed that UPLC-MS based-pattern recognition
      analysis approach can be used to quickly identify TCM multicomponent and for
      standardization of herbal preparations. 

PMID- 25981926
TI  - Novel sequential stress model for functional dyspepsia: Efficacy of the herbal
      preparation STW5.
AB  - BACKGROUND: Many screening procedures for agents with potential usefulness in
      functional dyspepsia (FD) rely on animals exposed to stress early in life
      (neonatal maternal separation, NMS) or in adulthood (restraint stress, RS).
      PURPOSE: Since many clinical cases of FD have been associated with stress in
      early life followed by stress in adulthood, a sequential model simulating the
      clinical situation is described. To explore the validity of the model, the
      efficacy of STW5, a multicomponent herbal preparation of proven usefulness in FD,
      was tested. STUDY DESIGN/METHODS: A sequential stress model established where
      rats are exposed to NMS after birth followed later by RS in adulthood. Stress
      hormones and ghrelin were measured in plasma, while responsiveness of stomach
      fundus strips to smooth muscle stimulants and relaxants was assessed ex-vivo. The
      effectiveness of treatment with STW5 a few days before and during exposure to RS
      in preventing changes induced by the stress model is reported and compared to its
      efficacy when used in animals subjected to RS alone. RESULTS: Responses to both
      stimulants and relaxants were reduced to various extents in the studied models,
      but treatment with STW5 tended to normalize gastric responsiveness. Plasma levels
      of ghrelin, corticosterone releasing factor, and corticosterone were raised by RS
      as well as the sequential model. Treatment with STW5 tended to prevent the
      deranged parameters. CONCLUSION: The sequential stress model has a place in drug
      screening for potential usefulness in FD as it simulates more the clinical
      setting. Furthermore, the findings shed more light on the mechanisms of action of
      STW5 in FD.

PMID- 25981927
TI  - Safety and efficacy of the switch to generic mycophenolate mofetil and tacrolimus
      in heart transplant patients.
AB  - BACKGROUND: Generic immunosuppressants may offer economic advantages, but their
      use is still controversial. At our center, 55 heart transplant patients were
      switched from CellCept((r)) to Myfenax Teva((r)) (MT) (n = 51, 18% female, 8.1 +/
      6.6 yr post-transplantation) and/or Prograf((r)) to Tacrolimus Sandoz((r)) (TS)
      (n = 17, 41% female, 6.6 +/- 5.8 yr post-transplantation). METHODS: We conducted
      an acute monitoring and a retrospective follow-up with regard to safety and
      efficacy. Acute cellular rejections (ACRs) on endomyocardial biopsies (EMBs) four
      wk after the MT switch were specifically compared to a matched retrospective
      control group. RESULTS: Tacrolimus C0 levels (TS switch) as well as hemoglobin,
      leukocytes, and thrombocytes (MT switch) did not change (p = NS) during the three
      wk after each respective switch (8.7 +/- 2.9 vs. 8.4 +/- 1.9 MUg/L, 129.1 +/-
      12.6 vs. 130.1 +/- 12.8 g/L, 6.3 vs. 6.2 * 10(9) /L, and 217.4 +/- 56.6 vs. 219.3
      +/- 61.8 * 10(9) /L, respectively). 0% of the EMBs in the MT switch vs. 3% of the
      EMBs in the control group showed ACR>grade 1R (p = NS). After six months,
      survival was 96% (MT switch) and 100% (TS switch), and the frequency of severe
      ACR was low. Safety parameters measured at the next annual follow-up were also
      stable following each switch. CONCLUSION: Switching to MT and/or TS several years
      after heart transplantation appeared safe in the short-term perspective, showing
      no detectable changes in tacrolimus C0 levels, safety or efficacy, during an
      average follow-up of six months.

PMID- 25981928
TI  - Pressure ulcer and patient characteristics--A point prevalence study in a
      tertiary hospital of India based on the European Pressure Ulcer Advisory Panel
      minimum data set.
AB  - BACKGROUND: Pressure ulcers is a frequent problem in hospitalized patients.
      Several prevalence studies have been conducted across the globe. Little
      information is available regarding prevalence of pressure ulcers in India.
      PURPOSE: The aim was to identify the prevalence of pressure ulcers in one of the
      tertiary hospital in northern India and the factors associated with its
      development. DESIGN: A cross sectional point prevalence study. INSTRUMENTS:
      European Pressure Ulcer Advisory Panel (EPUAP) data collection form. METHODS:
      Ethics approval was obtained prior to start of the study. Total of 358 patients
      were enrolled in the study. All patients above 18 years of age admitted in
      intensive care units and wards were included in the study. Patients admitted in
      emergency, day care, coronary care unit were excluded because of their short
      duration of hospital stay (varies from 24 to 72 h usually). All patients admitted
      before midnight on the predetermined day were included. The Braden scale was used
      to identify the risk of developing pressure ulcers. European Pressure ulcer
      advisory panel (EPUAP) minimum data set was used to collect prevalence data.
      RESULTS: The overall prevalence rate was 7.8%.The sacrum and heel were more
      commonly affected. Grade III pressure ulcers were the most common (42.8%).
      CONCLUSION: The pressure ulcer prevalence rate in our hospital was lower than
      that published in international studies. Severe forms of pressure ulcers were
      commonly encountered This data provides background information that may help us
      in developing protocols for applying effective practices for prevention of
      pressure ulcers.

PMID- 25981929
TI  - Segregation versus colocalization: orthogonally functionalized binary
      micropatterned substrates regulate the molecular distribution in focal adhesions.
AB  - Orthogonally functionalized binary micropatterned substrates are produced using a
      novel protocol. The use of adequate peptido-mimetics enables an unprecedented
      segregation of purified alphavbeta3 and alpha5beta1 integrins in adjacent
      microislands and evidences the preference of U2OS cells to colocalize such
      receptors. Moreover, this tendency can be altered by varying the geometry and
      composition of the micropatterns. 

PMID- 25981930
TI  - Mycoplasma hyopneumoniae infections in peri-weaned and post-weaned pigs in
      Belgium and The Netherlands: Prevalence and associations with climatic
      conditions.
AB  - Mycoplasma hyopneumoniae (M. hyo) is an important pathogen in modern intensive
      pig farming in Europe. The objectives of the present study were (1) to use the
      tracheobronchial swab (TBS) technique to obtain data on the distribution of M.
      hyo infections in recently weaned pigs in Belgium and The Netherlands, and (2) to
      look for associations between infection prevalence and specific climatic
      conditions. One hundred and seventy-six pig herds were randomly selected and 30
      piglets sampled on each farm: 18 at 3-5 weeks of age and 12 at 6-11 weeks. Mucus
      collected from the tracheobronchial bifurcation and suspended in saline was
      subjected to PCR analysis for M. hyo. In 27% of herds (n= 44) at least one piglet
      tested positive for M. hyo at 3-5 weeks of age, and 29% (n= 47) at 6-11 weeks of
      age. The individual animal prevalence at the two ages was 7.1% and 10.9%,
      respectively. The probability of 3-5 week old piglets being M. hyo-positive was
      negatively associated with the precipitation rate (odds ratio [OR] = 0.971)
      during the week preceding the sampling. In the older post-weaning group, the odds
      of being M. hyo-positive at piglet level were significantly affected by season
      (OR of detection during autumn compared to summer 20.9). Thus, under Belgian and
      Dutch field conditions, piglets may be infected with M. hyo very early in life,
      with prevalence increasing further during the post-weaning period.

PMID- 25981931
TI  - The use of antimicrobial agents in broiler chickens.
AB  - Antimicrobial agents are essential tools for treating and controlling bacterial
      infections in poultry production. Veterinarians have a huge responsibility when
      using antimicrobials in poultry producing meat and eggs for human consumption.
      The term 'judicious use' of antimicrobials implies the optimal selection of drug,
      dose and duration of antimicrobial treatment, along with a reduction in
      inappropriate and excessive use as a means of slowing the emergence of
      antimicrobial resistance. The proper use of antimicrobials depends on the
      knowledge of interrelationships between bacteria, antimicrobial, host and
      consumer. This article reviews the anatomical-physiological features of poultry
      relating to drug disposition as well as the pharmacological and therapeutic
      characteristics of the most commonly used antimicrobials in broiler chickens.
      Doses frequently employed for flock treatment are presented as are accepted
      withdrawal times. 

PMID- 25981932
TI  - Anti-tumour effect of metformin in canine mammary gland tumour cells.
AB  - Metformin is an oral hypoglycaemic drug used in type 2 diabetes. Its
      pharmacological activity reportedly involves mitochondrial respiratory complex I,
      and mitochondrial respiratory complex inhibitors have a strong inhibitory effect
      on the growth of metastatic canine mammary gland tumour (CMGT) cell lines. It is
      hypothesised that metformin has selective anti-tumour effects on metastatic CMGT
      cells. The aim of this study was to investigate the in vitro effect of metformin
      on cell growth, production of ATP and reactive oxygen species (ROS), and the AMP
      activated protein kinase (AMPK) mammalian target of rapamycin (mTOR) pathway in
      two CMGT clonal cell lines with different metastatic potential. In addition,
      transcriptome analysis was used to determine cellular processes disrupted by
      metformin and in vivo anti-tumour effects were examined in a mouse xenograft
      model. Metformin inhibited CMGT cell growth in vitro, with the metastatic clone
      (CHMp-5b) displaying greater sensitivity. ATP depletion and ROS elevation were
      observed to a similar extent in the metastatic and non-metastatic (CHMp-13a) cell
      lines after metformin exposure. However, subsequent AMPK activation and mTOR
      pathway inhibition were prominent only in metformin-insensitive non-metastatic
      cells. Microarray analysis revealed inhibition of cell cycle progression by
      metformin treatment in CHMp-5b cells, which was further confirmed by Western
      blotting and cell cycle analysis. Additionally, metformin significantly
      suppressed tumour growth in xenografted metastatic CMGT cells. In conclusion,
      metformin exhibited an anti-tumour effect in metastatic CMGT cells through AMPK
      independent cell cycle arrest. Its mechanism of action differed in the non
      metastatic clone, where AMPK activation and mTOR inhibition were observed.

PMID- 25981933
TI  - Veterinary interventional oncology: from concept to clinic.
AB  - Interventional radiology (IR) involves the use of contemporary imaging modalities
      to gain access to different structures in order to deliver materials for
      therapeutic purposes. Veterinarians have been expanding the use of these
      minimally invasive techniques in animals with a variety of conditions involving
      all of the major body systems. Interventional oncology (IO) is a growing
      subspecialty of IR in human medicine used (1) to restore patency to malignant
      obstructions through endoluminal stenting, (2) to provide dose escalations to
      tumors without increasing systemic chemotherapy toxicities via superselective
      transarterial chemotherapy delivery, (3) to stop hemorrhage or reduce blood flow
      to tumors via transarterial embolization or chemoembolization, and (4) to provide
      therapies for those cancers with no safe or effective alternative options. This
      review provides a brief introduction to a few of the techniques currently
      available to veterinarians for cancer treatment. For each technique, the concept
      for improved palliation, patient quality of life, or tumor control is presented,
      followed by the most current veterinary clinical information available. Although
      promising, more studies will be necessary to determine if veterinary IO will
      provide the same benefits as has already been demonstrated in oncology care in
      humans. 

PMID- 25981934
TI  - Inflammation and cancer: till death tears them apart.
AB  - Advances in biotechnology have enabled the collection of an immeasurable amount
      of information from genomic, transcriptomic, metabolomic and proteomic studies of
      tumours within their microenvironments. The dissection of cytokine and chemokine
      networks has provided new clues to the interactions between cancer cells and
      their surrounding inflammatory landscape. To bridge the gap between chronic
      inflammation and cancer, dynamic participants in the tumour microenvironment have
      been identified, including tumour-associated macrophages (TAMs) and regulatory T
      cells (Tregs). Both of these cell types are notable for their ability to cause
      immunosuppressive conditions and support the evasion of tumour immune
      surveillance. It is clear now that the tumour-promoting inflammatory environment
      has to be included as one of the major cancer hallmarks. This review explores the
      recent advances in the understanding of cancer-related inflammation and how this
      is being applied to comparative oncology studies in humans and domestic species,
      such as the dog.

PMID- 25981935
TI  - Serum amyloid A, haptoglobin, and ferritin in horses with colic: Association with
      common clinicopathological variables and short-term outcome.
AB  - Equine colic may be associated with an acute phase response (APR). Measurement of
      acute phase proteins (APPs) allows the detection of an APR and may help
      clinicians in monitoring the disease; however, the role of APPs in colic is
      unclear. This study aimed to evaluate the clinical usefulness of serum amyloid A
      (SAA), haptoglobin and ferritin in combination with an extended
      clinicopathological profile in equine colic. The medical records of 54 horses
      were retrospectively selected. Horses were grouped based on outcome (survivors
      vs. non-survivors), diagnosis (ischaemic/strangulating vs. non-ischaemic/non
      strangulating), and treatment (medical treatment vs. surgery). Laboratory data
      were compared, and a logistic regression analysis was performed for outcome
      prediction upon admission. A high percentage of horses had abnormal SAA (29/54),
      haptoglobin (20/54), and ferritin (31/54) concentrations. In particular,
      haptoglobin was below the reference interval in 13/54 horses. Non-survivors had
      significantly decreased haptoglobin and increased ferritin concentrations
      compared with survivors. The ischaemic/strangulating group had significantly
      increased creatinine and ferritin and decreased haptoglobin concentrations
      compared with the non-ischaemic/non-strangulating group. Creatinine was the only
      significant predictor of mortality in the regression analysis. In conclusion,
      APPs including SAA, haptoglobin, and ferritin combined with clinicopathological
      variables may help clinicians to understand the pathogenesis of APR and underline
      potential complications of equine colic. The reduction in haptoglobin
      concentration may suggest haemolysis or muscle fibre damage; ferritin may
      indicate alteration in iron metabolism and tissue damage. Further prospective
      studies are needed to assess diagnostic and prognostic values of APPs in colic
      horses. 

PMID- 25981936
TI  - Polycyclic aromatic hydrocarbons in soils from urban to rural areas in Nanjing:
      Concentration, source, spatial distribution, and potential human health risk.
AB  - Polycyclic aromatic hydrocarbons (PAHs) have become a major type of pollutant in
      urban areas and their degree of pollution and characteristics of spatial
      distribution differ between various regions. We conducted a comprehensive study
      about the concentration, source, spatial distribution, and health risk of 16 PAHs
      from urban to rural soils in Nanjing. The mean total concentrations of 16 PAHs
      (?16PAHs) were 3330 ng g(-1) for urban soils, 1680 ng g(-1) for suburban soils,
      and 1060 ng g(-1) for rural soils. Five sources in urban, suburban, and rural
      areas of Nanjing were identified by positive matrix factorization. Their relative
      contributions of sources to the total soil PAH burden in descending order was
      coal combustion, vehicle emissions, biomass burning, coke tar, and oil in urban
      areas; in suburban areas the main sources of soil PAHs were gasoline engine and
      diesel engine, whereas in rural areas the main sources were creosote and biomass
      burning. The spatial distribution of soil PAH concentrations shows that old urban
      districts and commercial centers were the most contaminated of all areas in
      Nanjing. The distribution pattern of heavier PAHs was in accordance with ?16PAHs,
      whereas lighter PAHs show some special characteristics. Health risk assessment
      based on toxic equivalency factors of benzo[a]pyrene indicated a low
      concentration of PAHs in most areas in Nanjing, but some sensitive sites should
      draw considerable attention. We conclude that urbanization has accelerated the
      accumulation of soil PAHs and increased the environmental risk for urban
      residents.

PMID- 25981937
TI  - Tracing metal sources in core sediments of the artificial lake An-Dong, Korea:
      Concentration and metal association.
AB  - The concentration and source of trace metals in the artificial lake An-Dong,
      which has widespread abandoned mines and a Zn smelter upstream of the drainage
      basin, were investigated. Soils (18ea), stream waters (15ea) and sediments (15ea)
      in the main channel and five tributaries downstream of the Zn smelter towards the
      lake (~ 50 km downstream) were collected. And two core sediments were also taken
      from the middle of the lake. All samples were analyzed for trace metals in bulk
      and in a 1N HCl-leached fraction. Although the soil and stream sediments
      consisted mostly of sand-sized grains, concentrations of metals (Cu, Zn, Cd and
      Pb) were very high in all samples, including soils, stream waters and sediments
      at sites near the Zn smelter. However the metal concentrations decreased rapidly
      downstream, suggesting that the area of impact of the smelter lies within 5 km.
      Highly enriched metal concentrations were also found in dated core sediments from
      the lake; while the highest concentrations of Co, Ni, As, Cu, Zn, Cd and Pb were
      detected in the bottom of the sediment core (dated 1980) they decreased towards
      2000, and only Cu, Zn and Cd concentrations increased again in present-day
      samples. Since the temporal variation in metal concentrations appeared consistent
      with historical variation in ore mining and Zn smelter production rates, a model
      combining the production rates of each was developed, which estimated 3%, 12% and
      7% contributions from Zn smelter compared to ore mining production rate to levels
      of Cu, Cd and Zn, respectively, suggesting the different pathways by different
      sources. In addition, analysis of Cd/Zn and Cu/Zn ratios showed that
      contamination from ore mining decreased from 1980 to 2000, and smelting processes
      were most likely responsible for metal enrichment (Cu, Cd and Zn) from 2000 to
      the present.

PMID- 25981938
TI  - Technological and life cycle assessment of organics processing odour control
      technologies.
AB  - As more municipalities and communities across developed world look towards
      implementing organic waste management programmes or upgrading existing ones,
      composting facilities are emerging as a popular choice. However, odour from these
      facilities continues to be one of the most important concerns in terms of cost &
      effective mitigation. This paper provides a technological and life cycle
      assessment of some of the different odour control technologies and treatment
      methods that can be implemented in organics processing facilities. The
      technological assessment compared biofilters, packed tower wet scrubbers, fine
      mist wet scrubbers, activated carbon adsorption, thermal oxidization, oxidization
      chemicals and masking agents. The technologies/treatment methods were evaluated
      and compared based on a variety of operational, usage and cost parameters. Based
      on the technological assessment it was found that, biofilters and packed bed wet
      scrubbers are the most applicable odour control technologies for use in organics
      processing faculties. A life cycle assessment was then done to compare the
      environmental impacts of the packed-bed wet scrubber system, organic (wood-chip
      media) bio-filter and inorganic (synthetic media) bio-filter systems. Twelve
      impact categories were assessed; cumulative energy demand (CED), climate change,
      human toxicity, photochemical oxidant formation, metal depletion, fossil
      depletion, terrestrial acidification, freshwater eutrophication, marine
      eutrophication, terrestrial eco-toxicity, freshwater eco-toxicity and marine eco
      toxicity. The results showed that for all impact categories the synthetic media
      biofilter had the highest environmental impact, followed by the wood chip media
      bio-filter system. The packed-bed system had the lowest environmental impact for
      all categories. 

PMID- 25981939
TI  - Cost saving potential in cardiovascular hospital costs due to reduction in air
      pollution.
AB  - OBJECTIVE: We describe a methodological framework to estimate potential cost
      savings in Belgium for a decrease in cardiovascular emergency admissions
      (ischemic heart disease (IHD), heart rhythm disturbances (HRD), and heart
      failure) due to a reduction in air pollution. METHODS: Hospital discharge data on
      emergency admissions from an academic hospital were used to identify cases,
      derive risk functions, and estimate hospital costs. Risk functions were derived
      with case-crossover analyses with weekly average PM10, PM2.5, and NO2 exposures.
      The risk functions were subsequently used in a micro-costing analysis approach.
      Annual hospital cost savings for Belgium were estimated for two scenarios on the
      decrease of air pollution: 1) 10% reduction in each of the pollutants and 2)
      reduction towards annual WHO guidelines. RESULTS: Emergency admissions for IHD
      and HRD were significantly associated with PM10, PM2.5, and NO2 exposures the
      week before admission. The estimated risk reduction for IHD admissions was 2.44%
      [95% confidence interval (CI): 0.33%-4.50%], 2.34% [95% CI: 0.62%-4.03%], and
      3.93% [95% CI: 1.14%-6.65%] for a 10% reduction in PM10, PM2.5, and NO2
      respectively. For Belgium, the associated annual cost savings were estimated at ?
      5.2 million, ? 5.0 million, and ? 8.4 million respectively. For HRD, admission
      risk could be reduced by 2.16% [95% CI: 0.14%-4.15%], 2.08% [95% CI: 0.42%
      3.70%], and 3.46% [95% CI: 0.84%-6.01%] for a 10% reduction in PM10, PM2.5, and
      NO2 respectively. This corresponds with a potential annual hospital cost saving
      in Belgium of ? 3.7 million, ? 3.6 million, and ? 5.9 million respectively. If
      WHO annual guidelines for PM10 and PM2.5 are met, more than triple these amounts
      would be saved. DISCUSSION: This study demonstrates that a model chain of case
      crossover and micro-costing analyses can be applied in order to obtain estimates
      on the impact of air pollution on hospital costs.

PMID- 25981940
TI  - Transport of TiO2 nanoparticles in soil in the presence of surfactants.
AB  - This paper aimed to investigate the influences of surfactants on the nanoparticle
      transport behavior in soil. The transport behaviors of TiO2 nanoparticles (nTiO2)
      in soil with three different surfactants, including Triton X-100 (TX-100), sodium
      dodecylbenzene sulfonate (SDBS) and cationic cetyl trimethylammonium bromide
      (CTAB) were studied. Results showed that all the three surfactants decreased the
      mobility of nTiO2 in soil column, which were mainly caused by the strong
      adsorption of surfactants on soil and nTiO2. The inhibition order was as follows:
      CTAB>SDBS>TX-100. Combined effect experiments showed that when solution ionic
      strength (IS) increased, TX-100 or CTAB inhibited the mobility of nTiO2 in soil.
      However, the effect of SDBS on nTiO2 transport shifted from inhibition to
      facilitation when IS increased from 0.1 to 5mM. This was mainly attributed to the
      decreasing adsorption of SDBS on soil with increased IS, whereas the adsorption
      of TX-100 and CTAB was independent of IS. This innovative information motivates
      further insight into the role of surfactants on nanoparticle transport behavior
      in soil. 

PMID- 25981941
TI  - Fate of sulfonamide resistance genes in estuary environment and effect of
      anthropogenic activities.
AB  - With the exacerbating problem of antibiotic resistance, antibiotic resistance
      genes (ARGs) as emerging contaminants are found at elevated levels in inland
      aquatic environments, especially in regions of intensive agricultural and urban
      activity. However, little quantitative data exist on the migration and
      attenuation of ARGs in estuary ecosystem, which is central to predicting their
      fate after release into marine environment. Moreover, the relevance of multiple
      chemical contaminants and water quality constituents should be understood to
      amplify and attenuate antibiotic resistance levels. To determine the prevalence
      and examine the fate of sulfonamide ARGs (sul-ARGs) in two estuaries under
      different effects of anthropogenic activities, we analyzed the sul-ARGs (sul1,
      sul2, and sul3), class 1 integrons (int1), and bacterial biomass in surface water
      samples from Daliaohe and Liaohe river estuaries. We also evaluated five types of
      antibiotics, heavy metals, and various bulk water quality constituents. Results
      showed that sul-ARGs were widespread in Daliaohe and Liaohe river estuaries, but
      the distribution did not correlate with the concentration of sulfonamides.
      Significant reduction in the abundance of sul-ARGs was also observed with
      increased salinity. Nevertheless, the trend in the change of concentrations of
      sul-ARGs was different in the two estuaries. Statistical analysis of the results
      indicated that several metals were significantly and positively correlated with
      sul-ARGs. Pearson's correlation coefficients were higher than those determined
      between antibiotic residues and sul-ARGs. Furthermore, the relative abundance of
      sul-ARGs was significantly and positively correlated with the relative abundance
      of int1 which suggested that the propagation of sul-ARGs was facilitated by class
      1 integrons in estuaries. 

PMID- 25981942
TI  - Land use and land cover changes in Zezere watershed (Portugal)--Water quality
      implications.
AB  - To understand the relations between land use allocation and water quality
      preservation within a watershed is essential to assure sustainable development.
      The land use and land cover (LUC) within Zezere River watershed registered
      relevant changes in the last decades. These land use and land cover changes
      (LUCCs) have impacts in water quality, mainly in surface water degradation caused
      by surface runoff from artificial and agricultural areas, forest fires and burnt
      areas, and caused by sewage discharges from agroindustry and urban sprawl. In
      this context, the impact of LUCCs in the quality of surface water of the Zezere
      watershed is evaluated, considering the changes for different types of LUC and
      establishing their possible correlations to the most relevant water quality
      changes. The results indicate that the loss of coniferous forest and the increase
      of transitional woodland-shrub are related to increased water's pH; while the
      growth in artificial surfaces and pastures leads mainly to the increase of
      soluble salts and fecal coliform concentration. These particular findings within
      the Zezere watershed, show the relevance of addressing water quality impact
      driven from land use and should therefore be taken into account within the
      planning process in order to prevent water stress, namely within watersheds
      integrating drinking water catchments. 

PMID- 25981943
TI  - GHG and black carbon emission inventories from Mezquital Valley: The main energy
      provider for Mexico Megacity.
AB  - The greenhouse gases and black carbon emission inventory from IPCC key category
      Energy was accomplished for the Mezquital Valley, one of the most polluted
      regions in Mexico, as the Mexico City wastewater have been continuously used in
      agricultural irrigation for more than a hundred years. In addition,
      thermoelectric, refinery, cement and chemistry industries are concentrated in the
      southern part of the valley, near Mexico City. Several studies have reported air,
      soil, and water pollution data and its main sources for the region.
      Paradoxically, these sources contaminate the valley, but boosted its economic
      development. Nevertheless, no research has been done concerning GHG emissions, or
      climate change assessment. This paper reports inventories performed by the 1996
      IPCC methodology for the baseline year 2005. Fuel consumption data were derived
      from priority sectors such as electricity generation, refineries, manufacturing &
      cement industries, transportation, and residential use. The total CO2 emission
      result was 13,894.9 Gg, which constituted three-quarters of Hidalgo statewide
      energy category. The principal CO2 sources were energy transformation (69%) and
      manufacturing (19%). Total black carbon emissions were estimated by a bottom-up
      method at 0.66 Gg. The principal contributor was on-road transportation (37%),
      followed by firewood residential consumption (26%) and cocked brick manufactures
      (22%). Non-CO2 gas emissions were also significant, particularly SO2 (255.9 Gg),
      which accounts for 80% of the whole Hidalgo State emissions. Results demonstrated
      the negative environmental impact on Mezquital Valley, caused by its role as a
      Megacity secondary fuel and electricity provider, as well as by the presence of
      several cement industries.

PMID- 25981944
TI  - Occurrence of cyclophosphamide and ifosfamide in aqueous environment and their
      removal by biological and abiotic wastewater treatment processes.
AB  - Cytostatic drug residues in the aqueous environment are of concern due to their
      possible adverse effects on non-target organisms. Here we report the occurrence
      and removal efficiency of cyclophosphamide (CP) and ifosfamide (IF) by biological
      and abiotic treatments including advanced oxidation processes (AOPs).
      Cyclophosphamide was detected in hospital wastewaters (14-22,000 ng L(-1)),
      wastewater treatment plant influents (19-27 ng L(-1)) and effluent (17 ng L(-1)),
      whereas IF was detected only in hospital wastewaters (48-6800 ng L(-1)). The
      highest removal efficiency during biological treatment (attached growth biomass
      in a flow through bioreactor) was 59 +/- 15% and 35 +/- 9.3% for CP and IF,
      respectively. Also reported are the removal efficiencies of both compounds from
      wastewater using hydrodynamic cavitation (HC), ozonation (O3) and/or UV, either
      individually or in combination with hydrogen peroxide (H2O2). Hydrodynamic
      cavitation did not remove CP and IF to any significant degree. The highest
      removal efficiencies: 99 +/- 0.71% for CP and 94 +/- 2.4% for IF, were achieved
      using UV/O3/H2O2 at 5 g L(-1) for 120 min. When combined with biological
      treatment, removal efficiencies were >99% for both compounds. This is the first
      report of combined biological and AOP treatment of CP and IF from wastewater with
      a removal efficiency >99%.

PMID- 25981945
TI  - Effects of ketamine on psychomotor, sensory and cognitive functions relevant for
      driving ability.
AB  - Ketamine is a dissociative anesthetic. The misuse of ketamine as a recreational
      drug has increased over the last decade, especially in rave parties or clubs.
      Short-term ketamine pilot protocols have been undertaken for treatment-resistant
      depressive clients. In this study, we review and comment on the evidence relating
      to the potential of ketamine as a causative/contributory factor in traffic
      accidents. To determine the causal role of ketamine in traffic accidents, a
      literature search on the psychomotor, cognitive, visual and perceptual functions
      related to safe driving was conducted. Furthermore, to interpret related data
      better, an overview of ketamine and its congeners' clinical pharmacology issues,
      recreational psychoactive effects, and identification in biological specimens is
      also provided. 

PMID- 25981947
TI  - The interplay of holistic shape, local feature and color information in object
      categorization.
AB  - Although it is widely accepted that colors facilitate object and scene
      recognition under various circumstances, several studies found no effects of
      color removal in tasks requiring categorization of briefly presented animals in
      natural scenes. In this study, three experiments were performed to test the
      assumption that the discrepancy between empirical data is related to variations
      of the available meaningful global information such as object shapes and
      contextual cues. Sixty-one individuals categorized chromatic and achromatic
      versions of intact and scrambled images containing either cars or birds. While
      color removal did not affect the classification of intact stimuli, the
      recognition of moderately scrambled achromatic images was more difficult. This
      effect was accompanied by amplitude modulations of occipital event-related
      potentials emerging from approximately 150ms post-stimulus. Our results indicate
      that colors facilitate stimulus classification, but this effect becomes prominent
      only in cases when holistic processing is not sufficient for stimulus
      recognition. 

PMID- 25981946
TI  - Engineering strategies for the fermentative production of plant alkaloids in
      yeast.
AB  - Microbial hosts engineered for the biosynthesis of plant natural products offer
      enormous potential as powerful discovery and production platforms. However, the
      reconstruction of these complex biosynthetic schemes faces numerous challenges
      due to the number of enzymatic steps and challenging enzyme classes associated
      with these pathways, which can lead to issues in metabolic load, pathway
      specificity, and maintaining flux to desired products. Cytochrome P450 enzymes
      are prevalent in plant specialized metabolism and are particularly difficult to
      express heterologously. Here, we describe the reconstruction of the sanguinarine
      branch of the benzylisoquinoline alkaloid pathway in Saccharomyces cerevisiae,
      resulting in microbial biosynthesis of protoberberine, protopine, and
      benzophenanthridine alkaloids through to the end-product sanguinarine, which we
      demonstrate can be efficiently produced in yeast in the absence of the associated
      biosynthetic enzyme. We achieved titers of 676 MUg/L stylopine, 548 MUg/L cis-N
      methylstylopine, 252 MUg/L protopine, and 80 MUg/L sanguinarine from the
      engineered yeast strains. Through our optimization efforts, we describe genetic
      and culture strategies supporting the functional expression of multiple plant
      cytochrome P450 enzymes in the context of a large multi-step pathway. Our results
      also provided insight into relationships between cytochrome P450 activity and
      yeast ER physiology. We were able to improve the production of critical
      intermediates by 32-fold through genetic techniques and an additional 45-fold
      through culture optimization.

PMID- 25981948
TI  - Dabigatran Concentration: Variability and Potential Bleeding Prediction In "Real
      Life" Patients With Atrial Fibrillation.
AB  - Routine laboratory monitoring is currently not recommended in patients receiving
      dabigatran despite its considerable variation in plasma concentration. However,
      in certain clinical situations, measurements of the dabigatran effect may be
      desirable. We aimed to assess the variability of dabigatran trough and peak
      concentration and explore the potential relationship between dabigatran
      concentration and adverse events. We included 44 patients with atrial
      fibrillation who started treatment with dabigatran 150 mg (D150) or 110 mg (D110)
      twice daily. They contributed 170 trough and peak blood samples that were
      collected 2-4 and 6-8 weeks after dabigatran initiation. Plasma dabigatran
      concentration was measured by LC-MS/MS and indirectly, by selected coagulation
      tests. D110 patients were older (74 +/- 7 versus 68 +/- 6 years), had lower
      creatinine clearance (68 +/- 21 versus 92 +/- 24 mL/min) and higher CHA2 DS2 
      VASc score (3.1 +/- 1.3 versus 2.3 +/- 0.9) compared to D150 patients (all p <
      0.05), but both had similar dabigatran concentrations in both trough and peak
      samples. Dabigatran concentrations varied less in trough than in peak samples
      (17.0 +/- 13.6 versus 26.6 +/- 19.2%, p = 0.02). During the 12-month follow-up, 4
      patients on D150 and 6 on D110 suffered minor bleeding. There was no major
      bleeding or thromboembolic event. Patients with bleeding had significantly higher
      average trough dabigatran concentrations (93 +/- 36 versus 72 +/- 62 MUg/L, p =
      0.02) than patients without bleeding, while peak dabigatran values had no
      predictive value. Dabigatran dose selection according to the guidelines resulted
      in appropriate trough concentrations with acceptable repeatability. High trough
      concentrations may predispose patients to the risk of minor bleeding.

PMID- 25981949
TI  - Outcomes of curative nephrectomy against renal cell carcinoma based on a central
      pathological review of 914 specimens from the era of cytokine treatment.
AB  - BACKGROUND: The purpose of this study was to determine the state of modern
      practice with regard to renal cell carcinoma (RCC) outcomes and to assess the
      effects on survival of such clinical and pathological factors such as
      histological subtype (HS) and nuclear grade by conducting a central pathological
      review based on the current World Health Organization classification and the
      staging system of the American Joint Committee on Cancer/Union for International
      Cancer Control. METHODS: We collected glass slides and clinical data sets for 914
      cases of RCC treated with curative nephrectomy from 1995 to 2000. Overall (OS),
      cancer-specific (CSS), and relapse-free (RFS) survival were compared for HS and
      nuclear grades determined by a central pathology review board comprising 5 board
      certified pathologists, pathological staging, and a variety of clinical factors.
      RESULTS: The 5 and 7-year CSS in this study were 96 and 93 %, respectively,
      values superior to those reported in Western countries. Concordance between the
      original and reviewed HS and nuclear grades were 90.9 and 21.1 %, respectively.
      HS correlated with OS (P = 0.043) but was not an independent prognostic factor in
      the multivariate analysis (P = 0.820). Tumor size, Fuhrman grade, and
      infiltration type were common independent prognostic factors for OS, CSS, and
      RFS. CONCLUSIONS: This study revealed RCC outcomes in the era of cytokine
      treatment for metastasis. Central pathological review is an essential component
      of a multicenter study with long-term follow-up. Tumor size, Fuhrman grade, and
      infiltration type had much greater effects than HS on survival after curative
      nephrectomy.

PMID- 25981950
TI  - Post-operative pulmonary and shoulder function after sternal reconstruction for
      patients with chest wall sarcomas.
AB  - BACKGROUND: Sternal resection is occasionally required for patients with
      malignant tumors, particularly sarcomas, in the sternal region. Few reports have
      described post-operative respiratory and shoulder function after sternal
      resection for patients with bone and soft-tissue sarcomas. METHODS: Eight
      consecutive patients with bone and soft tissue sarcomas requiring sternal
      resection were the focus of this study. Chest wall was reconstructed with a non
      rigid or semi-rigid prosthesis combined, in most cases, with soft tissue flap
      reconstruction. Clinical outcomes investigated included complications, shoulder
      function, evaluated with Musculoskeletal Tumor Society-International Symposium of
      Limb Salvage system, and respiratory function, evaluated by use of spirometry.
      RESULTS: The anterior chest wall was reconstructed with non-rigid strings for 3
      patients and with polypropylene mesh for 5. There were no severe post-operative
      complications, for example surgical site infection or pneumonia. All 3 patients
      with non-rigid reconstruction experienced paradoxical breathing, whereas none
      with polypropylene mesh did so. Post-operatively, FEV(1)% was unchanged but %VC
      was significantly reduced (p = 0.01), irrespective of the reconstruction method
      used (strings or polypropylene mesh). Shoulder function was not impaired.
      CONCLUSIONS: Among patients undergoing sternal resection, post-operative shoulder
      function was excellent. Pulmonary function was slightly restricted, but not
      sufficiently so to interfere with the activities of daily living (ADL).
      Paradoxical breathing is a slight concern for non-rigid reconstruction.

PMID- 25981951
TI  - Contralateral limb deficit seven months after ACL-reconstruction: an analysis of
      single-leg hop tests.
AB  - BACKGROUND: Following ACL-reconstruction, the non-injured leg (NIL) is used as a
      reference to assess injured leg (IL) recovery. However, deficits have been
      reported in the NIL questioning its use as a reference. The aim of this study is
      to assess whether NIL deficits are present while jumping after ACL
      reconstruction. METHODS: Thirteen males who had undergone ACL-reconstruction and
      16 healthy subjects took part in the experiment. Jumping performance was assessed
      during a single and a triple hop for distance. Jumping performance, kinematic and
      kinetic data were recorded during single leg squat jumps. Values for both the NIL
      and the IL were compared to those of a control group (CG). RESULTS: Jumping
      performance for single and triple hop for distance and single leg squat jump was
      lower in the NIL than in the CG (p=0.004, p=0.002, and p=0.016, respectively).
      During the squat jump, the knee joint was more extended and the ankle plantar
      flexion was greater at take-off while the peak total moment was 15% lower in the
      NIL than in the CG (p=0.002, p=0.002, and p=0.009, respectively). We found
      consistent evolutions in the NIL and the IL compared to the CG for jumping
      performance, initial joint angles, and peak total moment during the squat jump,
      but the opposite was found for the ankle and knee joint angles at squat jump take
      off. CONCLUSIONS: Jumping strategies are impaired in the NIL after ACL-R during
      jump tasks with some deficits matching those observed in the IL and some specific
      to the NIL. LEVEL OF EVIDENCE: III, Case control study.

PMID- 25981952
TI  - Impact of cancer and chemotherapy on autonomic nervous system function and
      cardiovascular reactivity in young adults with cancer: a case-controlled
      feasibility study.
AB  - BACKGROUND: Preliminary evidence suggests cancer- and chemotherapy-related
      autonomic nervous system (ANS) dysfunction may contribute to the increased
      cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However,
      the reliability of these findings may have been jeopardized by inconsistent
      participant screening and assessment methods. Therefore, good laboratory
      practices must be established before the presence and nature of cancer-related
      autonomic dysfunction can be characterized. The purpose of this study was to
      assess the feasibility of conducting concurrent ANS and cardiovascular
      evaluations in young adult cancer patients, according to the following criteria:
      i) identifying methodological pitfalls and proposing good laboratory practice
      criteria for ANS testing in cancer, and ii) providing initial physiologic
      evidence of autonomic perturbations in cancer patients using the composite
      autonomic scoring scale (CASS). METHODS: Thirteen patients (mixed diagnoses) were
      assessed immediately before and after 4 cycles of chemotherapy. Their results
      were compared to 12 sex- and age-matched controls. ANS function was assessed
      using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia
      and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test)
      reactivity. Cardiovascular reactivity during exercise was assessed using a
      modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria
      addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy
      assessment potential, iv) test performance/tolerability, and v) identification
      and minimizing the influence of potentially confounding medication. T-tests and
      repeated measures ANOVAs were used to assess between- and within-group
      differences at baseline and follow-up. RESULTS: The overall success rate in
      achieving our feasibility criteria was 98.4 %. According to the CASS, there was
      evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in
      18.2 % of patients at follow-up, compared to 0 % of controls at baseline or
      follow-up. CONCLUSIONS: Results from our feasibility assessment suggest that the
      investigation of ANS function in young adult cancer patients undergoing
      chemotherapy is possible. To the best of our knowledge, this is the first study
      to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any
      cancer population. Moreover, we provide evidence of cancer- and chemotherapy
      related parasympathetic dysfunction - as a possible contributor to the
      pathogenesis of CV disease in cancer survivors.

PMID- 25981953
TI  - The Neuroprotective Effect of Tetramethylpyrazine Against Contusive Spinal Cord
      Injury by Activating PGC-1alpha in Rats.
AB  - Tetramethylpyrazine (TMP) has been suggested to have neuroprotective effects
      against spinal cord injury (SCI); however, few studies have examined these
      effects and the corresponding mechanism. Therefore, the present study aimed to
      investigate the neuroprotective effect and underlying mechanism of TMP against
      contusive SCI. Adult male Sprague-Dawley rats were randomly divided into Sham,
      normal saline (NS) and TMP groups. Each group was divided into subgroups
      according to the time of sacrifice: 1, 3, 7, 14, 21 and 28 days post-injury.
      Laminectomy was performed in all groups, followed by contusive SCI establishment
      in the TMP and NS groups. TMP (80 mg/kg) was injected thereafter daily from 3 to
      7 days post-injury in the TMP group, which was replaced by equal volume of normal
      saline in the NS group. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale
      was measured at different time points post-injury to appraise locomotor
      functional recovery. Quantitative real-time PCR and immunofluorescence were used
      to assess the spatio-temporal expression of peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha (PGC-1alpha), while western blot was adopted to
      detect the effect of TMP on PGC-1alpha. Neural apoptotic changes and neuronal
      survival were evaluated using the TUNEL method and Nissl staining, respectively.
      TMP treatment markedly increased PGC-1alpha expression, neuronal survival and BBB
      locomotor scores, while also reducing neural apoptosis. These results demonstrate
      that TMP is neuroprotective against contusive SCI, with the inhibition of neural
      apoptosis and increase of neuronal survival. The sustained expression of PGC
      1alpha may partially contribute to the TMP-mediated neuroprotective effect. 

PMID- 25981954
TI  - D1 Antagonists and D2 Agonists Have Opposite Effects on the Metabolism of
      Dopamine in the Rat Striatum.
AB  - The striatum is known to possess high levels of D1-like and D2-like receptors
      (D1Rs and D2Rs, respectively). We have previously shown that selective inhibition
      of D1Rs increases the dopaminergic metabolic response and proposed that this
      effect is associated with the concomitant activation of postsynaptic D2Rs by
      endogenous dopamine (DA). Here, we examined whether activation of D2Rs modulates
      the metabolism and synthesis of DA in the striatum. We used male Wistar rats to
      evaluate the effects of the systemic administration of a D2R agonist
      (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these
      compounds with pargyline on the inhibition of monoamine oxidase. DA and L-3,4
      dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-L-phenylalanine (L
      DOPA) content were measured using high performance liquid chromatography. The
      systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg,
      significantly (P < 0.05) increased DOPAC levels and the DOPAC/DA ratio. At 2, 4
      and 8 mg/kg, the administration of bromocriptine alone significantly (P < 0.05)
      decreased DOPAC levels, L-DOPA content and the DOPAC/DA ratio, whereas at 2
      mg/kg, it decreased DA levels. In both groups, co-administration of either SCH
      23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA
      ratio by approximately 70 % compared to the levels observed in the control
      groups. In conclusion, administration of the D2R agonist bromocriptine decreased
      dopaminergic synthesis and metabolism in the striatum; in contrast,
      administration of the D1R antagonist SCH-23390 induced the opposite effects. 

PMID- 25981955
TI  - Implications of soil mixing for NAPL source zone remediation: Column studies and
      modeling of field-scale systems.
AB  - Soil remediation is often inhibited by subsurface heterogeneity, which constrains
      contaminant/reagent contact. Use of soil mixing techniques for reagent delivery
      provides a means to overcome contaminant/reagent contact limitations.
      Furthermore, soil mixing reduces the permeability of treated soils, thus
      extending the time for reactions to proceed. This paper describes research
      conducted to evaluate implications of soil mixing on remediation of non-aqueous
      phase liquid (NAPL) source zones. The research consisted of column studies and
      subsequent modeling of field-scale systems. For column studies, clean influent
      water was flushed through columns containing homogenized soils, granular zero
      valent iron (ZVI), and trichloroethene (TCE) NAPL. Within the columns, NAPL
      depletion occurred due to dissolution, followed by either column-effluent
      discharge or ZVI-mediated degradation. Complete removal of TCE NAPL from the
      columns occurred in 6-8 pore volumes of flow. However, most of the TCE (>96%) was
      discharged in the column effluent; less than 4% of TCE was degraded. The low
      fraction of TCE degraded is attributed to the short hydraulic residence time (<4
      days) in the columns. Subsequently, modeling was conducted to scale up column
      results. By scaling up to field-relevant system sizes (>10 m) and reducing
      permeability by one-or-more orders of magnitude, the residence time could be
      greatly extended, potentially for periods of years to decades. Model output
      indicates that the fraction of TCE degraded can be increased to >99.9%, given
      typical post-mixing soil permeability values. These results suggest that
      remediation performance can be greatly enhanced by combining contaminant
      degradation with an extended residence time.

PMID- 25981956
TI  - Enteric purinergic signaling: Shaping the "brain in the gut".

PMID- 25981957
TI  - Identification and characterization of parasitism genes from the pinewood
      nematode Bursaphelenchus xylophilus reveals a multilayered detoxification
      strategy.
AB  - The migratory endoparasitic nematode Bursaphelenchus xylophilus, which is the
      causal agent of pine wilt disease, has phytophagous and mycetophagous phases
      during its life cycle. This highly unusual feature distinguishes it from other
      plant-parasitic nematodes and requires profound changes in biology between modes.
      During the phytophagous stage, the nematode migrates within pine trees, feeding
      on the contents of parenchymal cells. Like other plant pathogens, B. xylophilus
      secretes effectors from pharyngeal gland cells into the host during infection. We
      provide the first description of changes in the morphology of these gland cells
      between juvenile and adult life stages. Using a comparative transcriptomics
      approach and an effector identification pipeline, we identify numerous novel
      parasitism genes which may be important for the mediation of interactions of B.
      xylophilus with its host. In-depth characterization of all parasitism genes using
      in situ hybridization reveals two major categories of detoxification proteins,
      those specifically expressed in either the pharyngeal gland cells or the
      digestive system. These data suggest that B. xylophilus incorporates effectors in
      a multilayer detoxification strategy in order to protect itself from host defence
      responses during phytophagy. 

PMID- 25981960
TI  - Longitudinal changes in free-water within the substantia nigra of Parkinson's
      disease.
AB  - There is a clear need to develop non-invasive markers of substantia nigra
      progression in Parkinson's disease. We previously found elevated free-water
      levels in the substantia nigra for patients with Parkinson's disease compared
      with controls in single-site and multi-site cohorts. Here, we test the hypotheses
      that free-water levels in the substantia nigra of Parkinson's disease increase
      following 1 year of progression, and that baseline free-water levels in the
      substantia nigra predict the change in bradykinesia following 1 year. We
      conducted a longitudinal study in controls (n = 19) and patients with Parkinson's
      disease (n = 25). Diffusion imaging and clinical data were collected at baseline
      and after 1 year. Free-water analyses were performed on diffusion imaging data
      using blinded, hand-drawn regions of interest in the posterior substantia nigra.
      A group effect indicated free-water values were increased in the posterior
      substantia nigra of patients with Parkinson's disease compared with controls (P =
      0.003) and we observed a significant group * time interaction (P < 0.05). Free
      water values increased for the Parkinson's disease group after 1 year (P =
      0.006), whereas control free-water values did not change. Baseline free-water
      values predicted the 1 year change in bradykinesia scores (r = 0.74, P < 0.001)
      and 1 year change in Montreal Cognitive Assessment scores (r = -0.44, P = 0.03).
      Free-water in the posterior substantia nigra is elevated in Parkinson's disease,
      increases with progression of Parkinson's disease, and predicts subsequent
      changes in bradykinesia and cognitive status over 1 year. These findings
      demonstrate that free-water provides a potential non-invasive progression marker
      of the substantia nigra. 

PMID- 25981959
TI  - De novo point mutations in patients diagnosed with ataxic cerebral palsy.
AB  - Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but
      frequently considered to be caused by birth asphyxia. Genetic investigations are
      rarely performed in patients with cerebral palsy and there is little proven
      evidence of genetic causes. As part of a large project investigating children
      with ataxia, we identified four patients in our cohort with a diagnosis of ataxic
      cerebral palsy. They were investigated using either targeted next generation
      sequencing or trio-based exome sequencing and were found to have mutations in
      three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo
      and associated with increased paternal age. The mutations were shown to be
      pathogenic using a combination of bioinformatics analysis and in vitro model
      systems. This work is the first to report that the ataxic subtype of cerebral
      palsy can be caused by de novo dominant point mutations, which explains the
      sporadic nature of these cases. We conclude that at least some subtypes of
      cerebral palsy may be caused by de novo genetic mutations and patients with a
      clinical diagnosis of cerebral palsy should be genetically investigated before
      causation is ascribed to perinatal asphyxia or other aetiologies. 

PMID- 25981961
TI  - Expanding the spectrum of neuronal pathology in multiple system atrophy.
AB  - Multiple system atrophy is a sporadic alpha-synucleinopathy that typically
      affects patients in their sixth decade of life and beyond. The defining clinical
      features of the disease include progressive autonomic failure, parkinsonism, and
      cerebellar ataxia leading to significant disability. Pathologically, multiple
      system atrophy is characterized by glial cytoplasmic inclusions containing
      filamentous alpha-synuclein. Neuronal inclusions also have been reported but
      remain less well defined. This study aimed to further define the spectrum of
      neuronal pathology in 35 patients with multiple system atrophy (20 male, 15
      female; mean age at death 64.7 years; median disease duration 6.5 years, range
      2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal
      inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions,
      were determined across a wide spectrum of brain regions. A correlation matrix of
      pathologic severity also was calculated between distinct anatomic regions of
      involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus,
      forebrain and thalamus, anterior cingulate and neocortex, and white matter of
      cerebrum, cerebellum, and corpus callosum). The major finding was the
      identification of widespread neuronal inclusions in the majority of patients, not
      only in typical disease-associated regions (striatum, substantia nigra), but also
      within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain
      and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of
      region-specific susceptibility, independent of the clinical phenotype, and the
      severity of pathology was duration-dependent. Neuronal inclusions also were
      identified in regions not previously implicated in the disease, such as within
      cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy
      followed the stepwise anatomic progression of Lewy body-spectrum disease
      inclusion pathology in 25.7% of patients with multiple system atrophy, including
      a patient with visual hallucinations. Further, the presence of Lewy body-like
      inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was
      associated with cognitive impairment (P = 0.002). However, several cases had the
      presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus,
      deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease.
      Finally, interregional correlations (rho >= 0.6) in pathologic glial and neuronal
      lesion burden suggest shared mechanisms of disease progression between both
      discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types
      (neuronal and glial inclusions in frontal cortex and white matter, respectively).
      These findings suggest that in addition to glial inclusions, neuronal pathology
      plays an important role in the developmental and progression of multiple system
      atrophy. 

PMID- 25981958
TI  - Parallel basal ganglia circuits for voluntary and automatic behaviour to reach
      rewards.
AB  - The basal ganglia control body movements, value processing and decision-making.
      Many studies have shown that the inputs and outputs of each basal ganglia
      structure are topographically organized, which suggests that the basal ganglia
      consist of separate circuits that serve distinct functions. A notable example is
      the circuits that originate from the rostral (head) and caudal (tail) regions of
      the caudate nucleus, both of which target the superior colliculus. These two
      caudate regions encode the reward values of visual objects differently: flexible
      (short-term) values by the caudate head and stable (long-term) values by the
      caudate tail. These value signals in the caudate guide the orienting of gaze
      differently: voluntary saccades by the caudate head circuit and automatic
      saccades by the caudate tail circuit. Moreover, separate groups of dopamine
      neurons innervate the caudate head and tail and may selectively guide the
      flexible and stable learning/memory in the caudate regions. Studies focusing on
      manual handling of objects also suggest that rostrocaudally separated circuits in
      the basal ganglia control the action differently. These results suggest that the
      basal ganglia contain parallel circuits for two steps of goal-directed behaviour:
      finding valuable objects and manipulating the valuable objects. These parallel
      circuits may underlie voluntary behaviour and automatic skills, enabling animals
      (including humans) to adapt to both volatile and stable environments. This
      understanding of the functions and mechanisms of the basal ganglia parallel
      circuits may inform the differential diagnosis and treatment of basal ganglia
      disorders. 

PMID- 25981963
TI  - The MDM4/MDM2-p53-IGF1 axis controls axonal regeneration, sprouting and
      functional recovery after CNS injury.
AB  - Regeneration of injured central nervous system axons is highly restricted,
      causing neurological impairment. To date, although the lack of intrinsic
      regenerative potential is well described, a key regulatory molecular mechanism
      for the enhancement of both axonal regrowth and functional recovery after central
      nervous system injury remains elusive. While ubiquitin ligases coordinate
      neuronal morphogenesis and connectivity during development as well as after
      axonal injury, their role specifically in axonal regeneration is unknown.
      Following a bioinformatics network analysis combining ubiquitin ligases with
      previously defined axonal regenerative proteins, we found a triad composed of the
      ubiquitin ligases MDM4, MDM2 and the transcription factor p53 (encoded by TP53)
      as a putative central signalling complex restricting the regeneration program.
      Indeed, conditional deletion of MDM4 or pharmacological inhibition of MDM2/p53
      interaction in the eye and spinal cord promote axonal regeneration and sprouting
      of the optic nerve after crush and of supraspinal tracts after spinal cord
      injury. The double conditional deletion of MDM4-p53 as well as MDM2 inhibition in
      p53-deficient mice blocks this regenerative phenotype, showing its dependence
      upon p53. Genome-wide gene expression analysis from ex vivo fluorescence
      activated cell sorting in MDM4-deficient retinal ganglion cells identifies the
      downstream target IGF1R, whose activity and expression was found to be required
      for the regeneration elicited by MDM4 deletion. Importantly, we demonstrate that
      pharmacological enhancement of the MDM2/p53-IGF1R axis enhances axonal sprouting
      as well as functional recovery after spinal cord injury. Thus, our results show
      MDM4-MDM2/p53-IGF1R as an original regulatory mechanism for CNS regeneration and
      offer novel targets to enhance neurological recovery.media
      1vid110.1093/brain/awv125_video_abstractawv125_video_abstract. 

PMID- 25981962
TI  - First effects of rising amyloid-beta in transgenic mouse brain: synaptic
      transmission and gene expression.
AB  - Detecting and treating Alzheimer's disease, before cognitive deficits occur, has
      become the health challenge of our time. The earliest known event in Alzheimer's
      disease is rising amyloid-beta. Previous studies have suggested that effects on
      synaptic transmission may precede plaque deposition. Here we report how relative
      levels of different soluble amyloid-beta peptides in hippocampus, preceding
      plaque deposition, relate to synaptic and genomic changes. Immunoprecipitation
      mass spectrometry was used to measure the early rise of different amyloid-beta
      peptides in a mouse model of increasing amyloid-beta ('TASTPM', transgenic for
      familial Alzheimer's disease genes APP/PSEN1). In the third postnatal week,
      several amyloid-beta peptides were above the limit of detection, including
      amyloid-beta40, amyloid-beta38 and amyloid-beta42 with an intensity ratio of
      6:3:2, respectively. By 2 months amyloid-beta levels had only increased by 50%
      and although the ratio of the different peptides remained constant, the first
      changes in synaptic currents, compared to wild-type mice could be detected with
      patch-clamp recordings. Between 2 and 4 months old, levels of amyloid-beta40 rose
      by ~7-fold, but amyloid-beta42 rose by 25-fold, increasing the amyloid
      beta42:amyloid-beta40 ratio to 1:1. Only at 4 months did plaque deposition become
      detectable and only in some mice; however, synaptic changes were evident in all
      hippocampal fields. These changes included increased glutamate release
      probability (P < 0.001, n = 7-9; consistent with the proposed physiological
      effect of amyloid-beta) and loss of spontaneous action potential-mediated
      activity in the cornu ammonis 1 (CA1) and dentate gyrus regions of the
      hippocampus (P < 0.001, n = 7). Hence synaptic changes occur when the amyloid
      beta levels and amyloid-beta42:amyloid-beta40 ratio are still low compared to
      those necessary for plaque deposition. Genome-wide microarray analysis revealed
      changes in gene expression at 2-4 months including synaptic genes being strongly
      affected but often showing significant changes only by 4 months. We thus
      demonstrate that, in a mouse model of rising amyloid-beta, the initial deposition
      of plaques does not occur until several months after the first amyloid-beta
      becomes detectable but coincides with a rapid acceleration in the rise of amyloid
      beta levels and the amyloid-beta42:amyloid-beta40 ratio. Prior to acceleration,
      however, there is already a pronounced synaptic dysfunction, reflected as changes
      in synaptic transmission and altered gene expression, indicating that restoring
      synaptic function early in the disease progression may represent the earliest
      possible target for intervention in the onset of Alzheimer's disease. 

PMID- 25981964
TI  - Loss of endophilin-B1 exacerbates Alzheimer's disease pathology.
AB  - Endophilin-B1, also known as Bax-interacting factor 1 (Bif-1, and encoded by
      SH3GLB1), is a multifunctional protein involved in apoptosis, autophagy and
      mitochondrial function. We recently described a unique neuroprotective role for
      neuron-specific alternatively spliced isoforms of endophilin-B1. To examine
      whether endophilin-B1-mediated neuroprotection could be a novel therapeutic
      target for Alzheimer's disease we used a double mutant amyloid precursor protein
      and presenilin 1 (APPswe/PSEN1dE9) mouse model of Alzheimer's disease and
      observed that expression of neuron-specific endophilin-B1 isoforms declined with
      disease progression. To determine if this reduction in endophilin-B1 has a
      functional role in Alzheimer's disease pathogenesis, we crossed endophilin-B1(-/
      ) mice with APPswe/PSEN1dE9 mice. Deletion of endophilin-B1 accelerated disease
      onset and progression in 6-month-old APPswe/PSEN1dE9/endophilin-B1(-/-) mice,
      which showed more plaques, astrogliosis, synaptic degeneration, cognitive
      impairment and mortality than APPswe/PSEN1dE9 mice. In mouse primary cortical
      neuron cultures, overexpression of neuron-specific endophilin-B1 isoforms
      protected against amyloid-beta-induced apoptosis and mitochondrial dysfunction.
      Additionally, protein and mRNA levels of neuron-specific endophilin-B1 isoforms
      were also selectively decreased in the cerebral cortex and in the synaptic
      compartment of patients with Alzheimer's disease. Flow sorting of synaptosomes
      from patients with Alzheimer's disease demonstrated a negative correlation
      between amyloid-beta and endophilin-B1 levels. The importance of endophilin-B1 in
      neuronal function was further underscored by the development of synaptic
      degeneration and cognitive and motor impairment in endophilin-B1(-/-) mice by 12
      months. Our findings suggest that endophilin-B1 is a key mediator of a feed
      forward mechanism of Alzheimer's disease pathogenesis where amyloid-beta reduces
      neuron-specific endophilin-B1, which in turn enhances amyloid-beta accumulation
      and neuronal vulnerability to stress. 

PMID- 25981965
TI  - Global and regional functional connectivity maps of neural oscillations in focal
      epilepsy.
AB  - Intractable focal epilepsy is a devastating disorder with profound effects on
      cognition and quality of life. Epilepsy surgery can lead to seizure freedom in
      patients with focal epilepsy; however, sometimes it fails due to an incomplete
      delineation of the epileptogenic zone. Brain networks in epilepsy can be studied
      with resting-state functional connectivity analysis, yet previous investigations
      using functional magnetic resonance imaging or electrocorticography have produced
      inconsistent results. Magnetoencephalography allows non-invasive whole-brain
      recordings, and can be used to study both long-range network disturbances in
      focal epilepsy and regional connectivity at the epileptogenic zone. In
      magnetoencephalography recordings from presurgical epilepsy patients, we
      examined: (i) global functional connectivity maps in patients versus controls;
      and (ii) regional functional connectivity maps at the region of resection,
      compared to the homotopic non-epileptogenic region in the contralateral
      hemisphere. Sixty-one patients were studied, including 30 with mesial temporal
      lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31
      controls, patients with epilepsy had decreased resting-state functional
      connectivity in widespread regions, including perisylvian, posterior temporo
      parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global
      connectivity was related to longer duration of epilepsy and higher frequency of
      consciousness-impairing seizures (P < 0.01, linear regression). Furthermore,
      patients with increased regional connectivity within the resection site (n = 24)
      were more likely to achieve seizure postoperative seizure freedom (87.5% with
      Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or
      decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi
      square). Widespread global decreases in functional connectivity are observed in
      patients with focal epilepsy, and may reflect deleterious long-term effects of
      recurrent seizures. Furthermore, enhanced regional functional connectivity at the
      area of resection may help predict seizure outcome and aid surgical planning. 

PMID- 25981966
TI  - Food environments are relevant to recruitment and adherence in dietary
      modification trials.
AB  - Few studies have examined the built environment's role in recruitment to and
      adherence in dietary intervention trials. Using data from a randomized dietary
      modification trial of urban Latina breast cancer survivors, we tested the
      hypotheses that neighborhood produce access could act as a potential barrier
      and/or facilitator to recruitment, and that a participant's produce availability
      would be associated with increased fruit/vegetable intake, one of the
      intervention's targets. Eligible women who lived within a higher produce
      environment had a non-significant trend towards being more likely to enroll in
      the trial. Among enrollees, women who had better neighborhood access to produce
      had a non-significant trend toward increasing fruit/vegetable consumption. As
      these were not a priori hypotheses to test, we consider these analyses to be
      hypothesis generating and not confirmatory. Results suggest that participants'
      food environment should be considered when recruiting to and assessing the
      adherence of dietary intervention studies. 

PMID- 25981969
TI  - FcgammaR dependent mechanisms of cytotoxic, agonistic, and neutralizing antibody
      activities.
AB  - Given the widespread use of antibodies of the immunoglobulin G (IgG) class as
      cytotoxic, immunomodulatory, and neutralizing agents in the therapy of malignant,
      infectious, and autoimmune diseases, understanding the molecular and cellular
      mechanisms responsible for their therapeutic activity is of major importance.
      While Fcgamma receptors (FcgammaR) have well-appreciated roles as effectors of
      cytotoxic IgG activity, it has only recently become clear that the functionality
      of immunomodulatory and neutralizing IgG preparations also depends on cellular
      FcgammaRs. Here, we review current models of IgG activity in infectious and
      inflammatory settings, and examine the importance of cell type-specific
      expression of FcgammaRs in determining functional outcome. We discuss how this
      knowledge may be used to improve the activity of therapeutic antibody
      preparations and outline important areas of focus for future research. 

PMID- 25981970
TI  - Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1)
      provide insights into the role of sequence and conformation in Laskowski
      mechanism inhibition.
AB  - Laskowski inhibitors regulate serine proteases by an intriguing mode of action
      that involves deceiving the protease into synthesizing a peptide bond. Studies
      exploring naturally occurring Laskowski inhibitors have uncovered several
      structural features that convey the inhibitor's resistance to hydrolysis and
      exceptional binding affinity. However, in the context of Laskowski inhibitor
      engineering, the way that various modifications intended to fine-tune an
      inhibitor's potency and selectivity impact on its association and dissociation
      rates remains unclear. This information is important as Laskowski inhibitors are
      becoming increasingly used as design templates to develop new protease inhibitors
      for pharmaceutical applications. In this study, we used the cyclic peptide,
      sunflower trypsin inhibitor-1 (SFTI-1), as a model system to explore how the
      inhibitor's sequence and structure relate to its binding kinetics and function.
      Using enzyme assays, MD simulations and NMR spectroscopy to study SFTI variants
      with diverse sequence and backbone modifications, we show that the geometry of
      the binding loop mainly influences the inhibitor's potency by modulating the
      association rate, such that variants lacking a favourable conformation show
      dramatic losses in activity. Additionally, we show that the inhibitor's sequence
      (including both the binding loop and its scaffolding) influences its potency and
      selectivity by modulating both the association and the dissociation rates. These
      findings provide new insights into protease inhibitor function and design that we
      apply by engineering novel inhibitors for classical serine proteases, trypsin and
      chymotrypsin and two kallikrein-related peptidases (KLK5 and KLK14) that are
      implicated in various cancers and skin diseases. 

PMID- 25981971
TI  - Microinvasive breast cancer: pathological parameters, cancer subtypes
      distribution, and correlation with axillary lymph nodes invasion. Results of a
      large single-institution series.
AB  - BACKGROUND: Microinvasive breast cancer is a rare entity in which an invasive
      component not exceeding 1 mm is found, mostly in a ductal carcinoma in situ
      setting. Its diagnosis can be difficult and must rely upon immunohistochemistry
      markers. Many studies have analyzed pathological characteristics of this cancer
      to delineate its biological profile and possibly identify risk factors of
      axillary lymph nodes infiltration, which might be present and therefore
      clinically relevant. Starting from a relative large number of cases we aimed to
      analyze pathological data, cancer subtypes distribution, and their correlation to
      nodal metastasis, comparing our results to the existing recent literature.
      METHODS: All cases of microinvasive breast cancer were retrieved from
      institutional database from 1992 to 2014. Pathological parameters were analyzed
      for entire cohort. Moreover, cases submitted to standardized sentinel node biopsy
      in a restricted period, 2000-2014, were selected to correlate pathology and
      cancer subtype to axillary lymph nodes status. RESULTS: 174 cases (1.4 % of
      operated breast cancers) were evaluated in the larger period, 1992-2014. Neither
      specific pathological parameters were expressed nor a peculiar cancer subtype was
      represented. 126 cases were selected for axillary staging analysis. Eighteen
      cases (14.3 %) had lymph nodes metastasis, 10 ITCs (7.9 %), 3 micrometastases
      (2.4 %), and 5 macrometastases (4 %). An associated intraductal component of
      carcinoma over 20 mm in maximum dimension resulted significant at multivariate
      analysis, but only if including ITCs, while this risk factor was not reproduced
      for micro- and macrometastases only. CONCLUSIONS: Microinvasive breast cancer
      does not seem to have specific pathological and biological traits. An associated
      intraductal component of carcinoma >20 mm in size is a specific risk factor for
      ITCs nodal metastasis. Its clinical significance is anyway limited and therefore
      sentinel node biopsy should be performed case by case and not routinely.

PMID- 25981967
TI  - Immune mechanisms in inflammatory and degenerative eye disease.
AB  - It has recently been recognized that pathology of age-associated degenerative eye
      diseases such as adult macular degeneration (AMD), glaucoma and diabetic
      retinopathy, have strong immunological underpinnings. Attempts have been made to
      extrapolate to age-related degenerative disease insights from inflammatory
      processes associated with non-infectious uveitis, but these have not yet been
      sufficiently informative. Here we review recent findings on the immune processes
      underlying uveitis and those that have been shown to contribute to AMD,
      discussing in this context parallels and differences between overt inflammation
      and para-inflammation in the eye. We propose that mechanisms associated with
      ocular immune privilege, in combination with paucity of age-related antigen(s)
      within the target tissue, dampen what could otherwise be overt inflammation and
      result in the para-inflammation that characterizes age-associated
      neurodegenerative disease. 

PMID- 25981972
TI  - Erratum to: Unique miRNome during anthesis in drought-tolerant indica rice var.
      Nagina 22.

PMID- 25981968
TI  - Regulatory T cell identity: formation and maintenance.
AB  - T regulatory (Treg) cells are central to the maintenance of immune homeostasis.
      The transcription factor forkhead box P3 (Foxp3) is essential for specifying the
      Treg cell lineage during development, and continued expression of Foxp3 in mature
      Treg cells is necessary for suppressive function. Loss of Foxp3 expression in
      Treg cells is associated with autoimmune pathology. Here, we review recent
      insights into the mechanisms that maintain Treg cell stability and function, and
      place these findings within the broader understanding of mechanisms that
      establish Treg cell identity during development. We integrate emerging principles
      in Treg cell lineage maintenance with the mechanisms that allow Treg cells to
      sense and respond to varied inflammatory environments, and outline important
      areas of future inquiry in this context. 

PMID- 25981973
TI  - The importance of intimate partner violence and suicidal ideation in pregnant
      women.

PMID- 25981974
TI  - Enhanced optical transmission and Fano resonance through a nanostructured metal
      thin film.
AB  - Artificial and engineered nanostructures expand the degrees of freedom with which
      one can manipulate the intricate interplay of light and matter. Certain
      nanostructural arrangements in the excited state enable the efficient
      electromagnetic coupling of propagating light with localized fields. Here, we
      demonstrate that light transmitted through a nanostructured metal thin film
      without any apertures can be significantly enhanced. Distinct asymmetric Fano
      resonances are observed in the zero-order transmission spectra using an
      incoherent light source. The transmission efficiency surpasses that of a metal
      thin film with the same area and thickness at the resonance maxima. The
      transmission minima and the sharp resonance maxima bear a strong resemblance to
      the extraordinary optical transmission observed in sub-wavelength nanohole array
      structures The resonance wavelength closely matches the nanostructural
      periodicity. The sensitivity of the resonances to the surrounding medium and the
      transmission efficiency demonstrate the potential for use in energy harvesting,
      imaging, optical processing and sensing applications. 

PMID- 25981975
TI  - Simultaneous enhancement in mechanical strength, electrical conductivity, and
      electromagnetic shielding properties in PVDF-ABS blends containing PMMA wrapped
      multiwall carbon nanotubes.
AB  - A unique approach was adopted to drive the multiwall carbon nanotubes (MWNTs) to
      the interface of immiscible PVDF-ABS blends by wrapping the nanotubes with a
      mutually miscible homopolymer (PMMA). A tailor made interface with an improved
      stress transfer was achieved in the blends with PMMA wrapped MWNTs. This
      manifested in an impressive 108% increment in the tensile strength and 48%
      increment in the Young's modulus with 3 wt% PMMA wrapped MWNTs in striking
      contrast to the neat blends. As the PMMA wrapped MWNTs localized at the interface
      of PVDF-ABS blends, the electrical conductivity could be tuned with respect to
      only MWNTs, which were selectively localized in the PVDF phase, driven by
      thermodynamics. The electromagnetic shielding properties were assessed using a
      vector network analyser in a broad range of frequency, X-band (8-12 GHz) and Ku
      band (12-18 GHz). Interestingly, enhanced EM shielding was achieved by this
      unique approach. The blends with only MWNTs shielded the EM waves mostly by
      reflection however, the blends with PMMA wrapped MWNTs (3 wt%) shielded mostly by
      absorption (62%). This study opens new avenues in designing materials, which show
      simultaneous improvement in mechanical, electrical conductivity and EM shielding
      properties. 

PMID- 25981976
TI  - Quantitative description of thermodynamic and kinetic properties of the platelet
      factor 4/heparin bonds.
AB  - Heparin is the most important antithrombotic drug in hospitals. It binds to the
      endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin
      complexes which may cause a severe immune-mediated adverse drug reaction, so
      called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have
      been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin
      complexes have not been clearly understood. In this study, single molecule force
      spectroscopy (SMFS) is utilized to characterize the interaction of PF4 with
      heparins of defined length (5-, 6-, 8-, 12-, and 16-mers). Analysis of the force
      distance curves shows that PF4/heparin binding strength rises with increasing
      heparin length. In addition, two binding pathways in the PF4/short heparins (<=8
      mers) and three binding pathways in the PF4/long heparins (>=8-mers) are
      identified. We provide a model for the PF4/heparin complexes in which short
      heparins bind to one PF4 tetramer, while long heparins bind to two PF4 tetramers.
      We propose that the interaction between long heparins and PF4s is not only due to
      charge differences as generally assumed, but also due to hydrophobic interaction
      between two PF4s which are brought close to each other by long heparin. This
      complicated interaction induces PF4/heparin complexes more stable than other
      ligand-receptor interactions. Our results also reveal that the boundary between
      antigenic and non-antigenic heparins is between 8- and 12-mers. These
      observations are particularly important to understand processes in which PF4
      heparin interactions are involved and to develop new heparin-derived drugs. 

PMID- 25981978
TI  - Mechanistic Insight into the Stereochemical Control of Lactide Polymerization by
      Salan-Aluminum Catalysts.
AB  - Alkyl aluminum complexes of chiral salan ligands assembled around the 2,2'
      bipyrrolidine core form as single diastereomers that have identical
      configurations of the N donors. Active catalysts for the polymerization of
      lactide were formed upon the addition of benzyl alcohol. Polymeryl exchange
      between enantiomorphous aluminum species had a dramatic effect on the tacticity
      of the poly(lactic acid) (PLA) in the polymerization of racemic lactide (rac-LA):
      The enantiomerically pure catalyst of the nonsubstituted salan ligand led to
      isotactic PLA, and the racemic catalyst exhibited lower stereocontrol. The
      enantiomerically pure catalyst of the chloro-substituted salan ligand led to PLA
      with a slight tendency toward heterotacticity, whereas the racemic catalyst led
      to PLA of almost perfect heterotacticity following an insertion/auto
      inhibition/exchange mechanism. 

PMID- 25981977
TI  - Calcium Channel Mutations in Cardiac Arrhythmia Syndromes.
AB  - Voltage gated calcium channels are essential for cardiac physiology by serving as
      sarcolemma- restricted gatekeepers for calcium in cardiac myocytes. Activation of
      the L-type voltagegated calcium channel provides the calcium entry required for
      excitation-contraction coupling and contributes to the plateau phase of the
      cardiac action potential. Given these critical physiological roles, subtle
      disturbances in L-type channel function can lead to fatal cardiac arrhythmias.
      Indeed, numerous human arrhythmia syndromes have been linked to mutations in the
      L-type channel leading to gain-of-function or loss-of-function mutations. In this
      review, we discuss the current state of knowledge regarding these mutations
      present in Timothy Syndrome, Long and Short QT Syndromes, Brugada Syndrome and
      Early Repolarization Syndrome. We discuss the pathological consequences of the
      mutations, the biophysical effects of the mutations on the channel as well as
      possible therapeutic considerations and challenges for future studies.

PMID- 25981979
TI  - MDCT of interatrial septum.
AB  - ECG-gated cardiac multidetector row computed tomography (MDCT) allows precise
      analysis of the interatrial septum (IAS). This pictorial review provides a
      detailed description of the normal anatomy, variants and abnormalities of the IAS
      such as patent foramen ovale, congenital abnormalities such as atrial septal
      defects as well as tumors and tumoral-like processes that develop on the IAS. 

PMID- 25981980
TI  - Paediatric use of melatonin (Author reply to D. J. Kennaway).

PMID- 25981981
TI  - Nanoparticle analysis of cancer cells by light transmission spectroscopy.
AB  - We have measured the optical properties of cancer and normal whole cells and
      lysates using light transmission spectroscopy (LTS). LTS provides both the
      optical extinction coefficient in the wavelength range from 220 to 1100nm and (by
      spectral inversion using a Mie model) the particle distribution density in the
      size range from 1 to 3000nm. Our current work involves whole cells and lysates of
      cultured human oral cells in liquid suspension. We found systematic differences
      in the optical extinction between cancer and normal whole cells and lysates,
      which translate to different particle size distributions (PSDs) for these
      materials. Specifically, we found that cancer cells have distinctly lower
      concentrations of nanoparticles with diameters less than 100nm and have higher
      concentrations of particles with diameters from 100 to 1000nm-results that hold
      for both whole cells and lysates. We also found a power-law dependence of
      particle density with diameter over several orders of magnitude. 

PMID- 25981982
TI  - Intramural oesophageal bronchogenic cyst: a rare pathological finding.

PMID- 25981983
TI  - In vivo efficacy of human recombinant factor IX produced by the human hepatoma
      cell line HuH-7.
AB  - INTRODUCTION: Post-translational modifications of the CHO-cell-derived
      recombinant human factor IX (FIX) currently used for the treatment of hemophilia
      B (HB) are different from plasma derived FIX. Our previous studies described a
      rFIX (HIX) having better profile of post-translational modifications than rFIX
      produced by CHO cells. The aim of the study consisted to verify the improved post
      translational modifications effect of HIX on in vivo recovery. MATERIALS AND
      METHODS: HIX has been produced in a bioreactor and then purified from
      supernatants. In vitro activation and activity were evaluated measured by
      thrombin generation tests (TGT) and compared to commercial molecules,
      Benefix((r)) , Mononine((r)) . The three molecules were then administrated (i.v.)
      to FIX-knockout mice and two minutes after injection, blood samples were
      collected and subjected to human FIX-specific-ELISA and TGT. RESULTS: The
      clotting function of HIX, activation courses of HIX by FXIa and FVIIa-TF complex
      appear normal as did activation of Benefix((r)) , Mononine((r)) and TG constants
      of each FIX were equivalent. After injection to HB mice, circulating HIX did not
      present any significant difference in term of antigen value with Benefix((r)) .
      Intriguingly, TGT were clearly exhibiting a better velocity for HIX than
      Benefix((r)) and Mononine((r)) . These data suggested that HIX may improve in
      vivo coagulant efficacy in comparison with the two commercial FIX injected at the
      same dose. CONCLUSION: The study shows that HuH-7-derived-rFIX has better in vivo
      haemostatic activity in hemophilia B mice compared to the reference rFIX molecule
      despite similar in vivo recovery rates, suggesting that HuH-7 cells could
      represent an effective cellular system for production of rFIX.

PMID- 25981984
TI  - Effect of the season on the free phytoprostane content in Cornicabra extra virgin
      olive oil from deficit-irrigated olive trees.
AB  - BACKGROUND: The effect of regulated deficit irrigation (RDI) on the phytoprostane
      (PhytoP) content in extra virgin olive (Olea europaea L., cv. Cornicabra) oil
      (EVOO) was studied. During the 2012 and 2013 seasons, T0 plants were irrigated at
      100% ETc, while T1 and T2 plants were irrigated avoiding water deficit during
      phases I and III of fruit growth and saving water during the non-critical
      phenological period of pit hardening (phase II), developing a more severe water
      deficit in T2 plants. In 2013, a fourth treatment (T3) was also performed, which
      was similar to T2 except that water saving was from the beginning of phase II to
      15 days after the end of phase II. RESULTS: 9-F1t -PhytoP, 9-epi-9-F1t -PhytoP, 9
      epi-9-D1t -PhytoP, 9-D1t -PhytoP, 16-B1 -PhytoP and 9-L1 -PhytoP were present in
      Cornicabra EVOO, and their contents increased in the EVOO from RDI plants.
      CONCLUSION: Deficit irrigation during pit hardening or for a further period of 2
      weeks thereafter to increase irrigation water saving is clearly critical for EVOO
      composition because of the enhancement of free PhytoPs, which have potential
      beneficial effects on human health. The response of individual free PhytoPs to
      changes in plant water status was not as perceptible as expected, preventing
      their use as biomarkers of water stress.

PMID- 25981985
TI  - T1 and T2 values of human neonatal blood at 3 Tesla: Dependence on hematocrit,
      oxygenation, and temperature.
AB  - PURPOSE: Knowledge of blood T1 and T2 is of major importance in many applications
      of MRI in neonates. However, to date, there has not been a systematic study to
      examine neonatal blood T1/T2 relaxometry. This present study aims to investigate
      this topic. METHODS: Using freshly collected blood samples from human umbilical
      cord, we performed in vitro experiments under controlled physiological conditions
      to measure blood T1 and T2 at 3 Tesla (T) and their dependence on several
      factors, including hematocrit (Hct), oxygenation (Y) and temperature. RESULTS:
      The arterial T1 in neonates was 1825 +/- 184 ms (Hct = 0.42 +/- 0.08), longer
      than that of adult blood. Neonatal blood T1 was strongly dependent on Hct (P <
      0.001) and Y (P = 0.005), and the dependence of T1 on Y was more prominent at
      higher Hct. The arterial T2 of neonatal blood was 191 ms at an Hct of 0.42, which
      was also longer than adult blood. Neonatal blood T2 was positively associated
      with blood oxygenation and negatively associated with hematocrit level, and can
      be characterized by an exchange model. Neonatal blood T1 was also positively
      associated with temperature (P < 0.001). CONCLUSION: The values provided in this
      report may provide important reference and calibration information for sequence
      optimization and quantification of in vivo neonatal MRI studies.

PMID- 25981986
TI  - Characterization of flavonoid glycosides from rapeseed bee pollen using a
      combination of chromatography, spectrometry and nuclear magnetic resonance with a
      step-wise separation strategy.
AB  - To identify the structures of flavonoid glycosides in bee pollen collected from
      rapeseed plants (Brassica napus L.), we utilised an approach that combined liquid
      chromatography-diode array detector-electrospray ionization-mass spectrometry (LC
      DAD-ESI-MS) and nuclear magnetic resonance (NMR) technology with a step-wise
      separation strategy. We identified four constituents of high purity in rape bee
      pollen samples: (1) quercetin-3-O-beta-D-glucosyl-(2->l)-beta-glucoside, (2)
      kaempferol-3, 4'-di-O-beta-D-glucoside, (3) 5, 7, 4'-trihydroxy-3'-methoxyflavone
      3-O-beta-D-sophoroside and (4) kaempferol-3-O-beta-D-glucosyl-(2->l)-beta-D
      glucoside. This study will also provide useful reference standards for
      qualification and quantification of four flavonoid glycosides in natural
      products.

PMID- 25981987
TI  - Family with Legius syndrome (neurofibromatosis type 1-like syndrome).
AB  - Legius syndrome (Online Mendelian Inheritance in Man no. 611431) or
      neurofibromatosis type 1 (NF1)-like syndrome was first reported by Legius et al.
      in 2007. We herein report the first instance of Legius syndrome occurring in two
      female siblings in Japan. Both individuals presented cafe-au-lait macules and
      freckling. Mutation analysis revealed a mutation of c.349C>T resulting in
      p.Arg117* in the SPRED1 gene as the cause of the Legius syndrome. The National
      Institutes of Health criteria for NF1 are insufficient to rule out the condition.
      For this reason, and because the clinical course of each condition is quite
      different, we stress the need to differentiate Legius syndrome from NF1 clearly. 

PMID- 25981988
TI  - Upfront treatment of high-risk neuroblastoma with a combination of 131I-MIBG and
      topotecan.
AB  - BACKGROUND: (131)I-metaiodobenzylguanidine ((131) I-MIBG) has a significant anti
      tumor effect against neuroblastoma (NBL). Topotecan (TPT) can act as a radio
      sensitizer and can up-regulate (131) I-MIBG uptake in vitro in NBL. AIM:
      Determine the efficacy of the combination of (131) I-MIBG with topotecan in newly
      diagnosed high-risk (HR) NBL patients. METHODS: In a prospective, window phase II
      study, patients with newly diagnosed high-risk neuroblastoma were treated at
      diagnosis with two courses of (131) I-MIBG directly followed by topotecan (0.7
      mg/m(2) for 5 days). After these two courses, standard induction treatment (four
      courses of VECI), surgery and myeloablative therapy (MAT) with autologous stem
      cell transplantation (ASCT) was given. Response was measured after two courses of
      (131) I-MIBG-topotecan and post MAT and ASCT. Hematologic toxicity and harvesting
      of stem cells were analysed. Topoisomerase-1 activity levels were analysed in
      primary tumor material. RESULTS: Sixteen patients were included in the study;
      median age was 2.8 years. MIBG administered activity (AA) (median and range) of
      the first course was 0.5 (0.4-0.6) GBq/kg (giga Becquerel/kilogram) and of the
      second course 0.4 (0.3-0.5) GBq/kg. The overall objective response rate (ORR)
      after 2 * MIBG/TPT was 57%, the primary tumor RR was 94%, and bone marrow RR was
      43%. The ORR post MAT and ASCT was 57%. Hematologic grade four toxicity: after
      first and second (131) I-MIBG (platelets 25/33%, neutrophils 13/33%, and
      hemoglobin 25/7%). Topoisomerase-1 activity levels were increased in 10/10 (100%)
      measured tumors. CONCLUSIONS: Combination therapy with MIBG-topotecan is an
      effective window treatment in newly diagnosed high-risk neuroblastoma patients.

PMID- 25981989
TI  - Endometrial metastasis of lung adenocarcinoma: a report of two cases.
AB  - BACKGROUND: The female genital tract is an uncommon site of involvement for
      extragenital malignancies. Ovarian, vaginal, and cervical metastasis has been
      described in the literature. Uterine corpus and, particularly, endometrial
      involvement are exceedingly rare. As the incidence of lung cancer is rising in
      the female population, metastatic uterine involvement by lung cancer is also
      being reported in the medical literature. Here, we report two cases of
      endometrial metastasis from primary lung adenocarcinoma. CASE REPORT: The first
      case is a 55-year-old woman diagnosed with stage III lung adenocarcinoma who
      received initial treatment with sequential chemotherapy and radiotherapy, which
      resulted in complete response to treatment. However, patient was found to have
      recurrence soon after completion of initial treatment. Biopsy of a hypermetabolic
      lesion confirmed endometrial metastasis. The second case is a 51-year-old woman
      who presented with stage IV lung adenocarcinoma with metastasis to the uterus.
      EGFR mutation analysis of the lung mass and endometrial biopsy revealed epidermal
      growth factor receptor L858R mutation in exon 21. She had a positive response to
      EGFR-directed treatment of all areas of disease, including the uterus.
      CONCLUSIONS: Uterine metastasis from lung adenocarcinoma is uncommon and
      difficult to differentiate from primary uterine cancer. The possibility of lung
      cancer metastasis should be considered in patients who have adenocarcinoma on
      biopsy of uterine lesions.

PMID- 25981990
TI  - Review of the radiation exposure during screening of surgically implanted central
      venous access devices.
AB  - PURPOSE: Ionizing radiation is used for the insertion of surgically implanted
      venous access devices (SIVADs) with children at the highest risk of cumulative
      radiation effects from these procedures. This study examines the radiation dose
      in a pediatric population during intraoperative radiological screening. METHODS:
      A retrospective study looked at all pediatric patients in a tertiary hospital
      between January 2008 and January 2014 who had a surgically implanted venous
      access device inserted using intraoperative fluoroscopy. Patient demographics,
      reason for SIVAD insertion, the type and method of insertion, fluoroscopy time
      and radiation dose area product were determined. RESULTS: A total of 505 patients
      had 682 SIVADs inserted, with 123 patients receiving multiple SIVAD over the six
      year period. There were two types of SIVAD inserted, 492 were totally implanted
      venous access devices (TIVAD) and 190 were tunneled central venous catheters
      (cuffed central line). Five hundred seven of the SIVAD inserted recorded the dose
      area product and fluoroscopy time. The median time for screening was 5seconds
      (range 1 to 275seconds) and the median dose area product was 0.00352mGym(2)
      (range 0.000001mGym(2) to 0.28mGym(2)). Of the 507 SIVAD that recorded the
      radiation data, 479 were open surgical cut-down insertion and 27 were
      percutaneous insertion. Percutaneously inserted surgically implanted venous
      access devices (mean 0.0060mGym(2)) had a longer dose area product than open
      insertion (mean 0.0034mGym(2); p=0.05). CONCLUSION: Screening of SIVAD involves
      low levels of radiation exposure and is comparable to a chest x-ray or a
      transatlantic flight. The excess lifetime cancer risk to patients is estimated to
      be very low and is considered to be outweighed by the benefits of insertion. Open
      surgical cut-down insertion has a significantly reduced radiation exposure
      compared to percutaneous techniques. Although radiation dose is higher with
      percutaneous procedures, the clinical effects are considered minimal, and the
      resultant radiation risk is estimated to be very low. Radiation dose should not
      determine technique of insertion of SIVAD.

PMID- 25981991
TI  - A new approach for persistent cloaca: Laparoscopically assisted anorectoplasty
      and modified repair of urogenital sinus.
AB  - PURPOSE: The aim of this study is to describe the surgical technique and evaluate
      midterm outcomes of the technique: laparoscopically assisted anorectoplasty
      (LAARP) and modified repair of urogenital sinus. METHOD: Seven patients with
      persistent cloaca underwent LAARP and modified repair of urogenital sinus between
      November 2005 and December 2010. The ages of the patients at the time of
      operation were 6 months to 15 years. Distal colostogram and micturating cystogram
      were performed preoperatively to identify the type of persistent cloaca. The
      rectal pouch was above the pubococcygeal line in all patients. The operations
      were carried out using 3 trocars. CO2 pressure was maintained at 8-12 mm Hg.
      RESULT: Laparoscopically assisted anorectoplasty and modified repair of
      urogenital sinus were successfully performed in all cases. Mean operation time
      was 125.7+/-8.4 minutes (range, 110-135 minutes). Intraoperative blood loss was
      minimal. There were no intraoperative complications. Follow-up was obtained in
      all patients. The median follow-up period was 5.7+/-2.1years (range, 4-9 years).
      Mucosal prolapse occurred in 2 cases (28.6%). No urethrovaginal fistula, acquired
      anorectal atresia or urethral injury was observed. Only 1 patient (14.3%) was
      incontinent of urine occasionally but urine retention or vesicoureteral reflux
      was not observed. Two patients (28.5%) had 2-4 stools per day but no social
      problem. Only 1 patient (14.3%) had constipation and required laxatives.
      CONCLUSION: Anoplasty, vaginoplasty and urethroplasty can be performed
      simultaneously in patients with persistent cloaca through LAARP and modified
      repair of urogenital sinus.

PMID- 25981992
TI  - Which properties of cutinases are important for applications?
AB  - Cutinases (EC 3.1.1.74) are extracellular enzymes that belong to alpha/beta
      hydrolases. They are serine esterases with the classical Ser-His-Asp triad
      similar to several lipases and serine proteases. In nature, cutinases catalyse
      the hydrolysis of the polyesters of the cuticle and the suberin layers, which
      protect plant surfaces. Cutinase production is typical for plant pathogenic
      fungi, but also, bacterial cutinases and cutinases from plant pollen have been
      discovered. Cutinases are promiscuous esterases catalysing reactions with a wide
      range of different substrates, such as short-chain soluble esters, water
      insoluble medium and long-chain triacylglycerols, polyesters and waxes. In the
      current work, an overview is given on suggested applications of cutinases in the
      textile industry, in laundry detergents, in processing of biomass and food, in
      biocatalysis and in detoxification of environmental pollutants. The applications
      are discussed from the point of view of cutinase properties-which properties of
      cutinases are already advantageous and which would be desired. In addition,
      improvements that have been made on cutinase performance by protein and reaction
      engineering are reviewed. 

PMID- 25981993
TI  - Elucidating carbon uptake from vinyl chloride using stable isotope probing and
      Illumina sequencing.
AB  - Vinyl chloride (VC), a known human carcinogen, is a common and persistent
      groundwater pollutant at many chlorinated solvent contaminated sites. The
      remediation of such sites is challenging because of the lack of knowledge on the
      microorganisms responsible for in situ VC degradation. To address this, the
      microorganisms involved in carbon assimilation from VC were investigated in a
      culture enriched from contaminated site groundwater using stable isotope probing
      (SIP) and high-throughput sequencing. The mixed culture was added to aerobic
      media, and these were amended with labeled ((13)C-VC) or unlabeled VC ((12)C-VC).
      The cultures were sacrificed on days 15, 32, and 45 for DNA extraction. DNA
      extracts and SIP ultracentrifugation fractions were subject to sequencing as well
      as quantitative PCR (qPCR) for a functional gene linked to VC-assimilation
      (etnE). The gene etnE encodes for epoxyalkane coenzyme M transferase, a critical
      enzyme in the pathway for VC degradation. The relative abundance of phylotypes
      was compared across ultracentrifugation fractions obtained from the (13)C-VC- and
      (12)C-VC-amended cultures. Four phylotypes were more abundant in the heavy
      fractions (those of greater buoyant density) from the (13)C-VC-amended cultures
      compared to those from the (12)C-VC-amended cultures, including Nocardioides,
      Brevundimonas, Tissierella, and Rhodoferax. Therefore, both a previously
      identified VC-assimilating genus (Nocardioides) and novel microorganisms were
      responsible for carbon uptake. Enrichment of etnE with time was observed in the
      heavy fractions, and etnE sequences illustrated that VC-assimilators harbor
      similar Nocardioides-like etnE. This research provides novel data on the
      microorganisms able to assimilate carbon from VC. 

PMID- 25981994
TI  - Detection of 2,4-dinitrotoluene and 2,4,6-trinitrotoluene by an Escherichia coli
      bioreporter: performance enhancement by directed evolution.
AB  - The use of bacterial bioreporters for the detection of buried landmines and other
      explosive devices has been promoted for over 25 years, and several bacterial
      sensor strains capable of detecting traces of either 2,4,6-trinitrotoluene (2,4,6
      TNT) or 2,4-dinitrotoluene (2,4-DNT) have since been reported. In all cases,
      however, detection sensitivity failed to reach the levels required to reliably
      sense the minute concentrations of 2,4-DNT vapors expected to exist in the soil
      above buried landmines. Here, we report on the application of a directed
      evolution process to enhance the performance of a previously described E. coli
      based bioreporter harboring a plasmid-borne genetic fusion between the yqjF gene
      promoter and either luxCDABE or gfp genes, generating bioluminescent or
      fluorescent signals, respectively, in the presence of either 2,4,6-TNT or its
      main "signature" compound, 2,4-DNT. We have performed four sequential rounds of
      random mutagenesis to the yqjF promoter region, yielding a fourth-generation
      sensor that displayed significantly improved 2,4-DNT detection characteristics
      compared to the wild-type and to previous generations. Luminescence intensity in
      the presence of aqueous 2,4-DNT increased over 3000-fold, response ratios were
      improved over 50-fold, detection threshold was reduced by 75 %, and response time
      was cut down to half. These features were manifested also upon exposure to 2,4
      DNT vapors or to 2,4-DNT and 2,4,6-TNT buried in sand. An analysis of the point
      mutations accumulated in the course of this process indicated that the major
      contributors to these effects were manipulations of the -35 element of the yqjF
      gene promoter.

PMID- 25981995
TI  - Elimination of carbon catabolite repression in Clostridium acetobutylicum--a
      journey toward simultaneous use of xylose and glucose.
AB  - The industrial Gram-positive anaerobe Clostridium acetobutylicum is a valued
      acetone, butanol, and ethanol (ABE) solvent producer that is able to utilize a
      vast array of carbon sources in fermentation. When glucose is present in the
      growth medium, however, C. acetobutylicum, like many Gram-positive organisms,
      exhibits biphasic growth characteristics in which glucose is used preferentially
      over secondary carbon sources, a phenomenon known as carbon catabolite repression
      (CCR). The secondary carbon source is only utilized when the supply of glucose is
      exhausted, resulting in inefficient use of complex carbon sources. As biofuel
      production is sought from cheap feedstock, attention has turned to
      lignocellulosic biomass. Growth of C. acetobutylicum on lignocellulose, however,
      can be limited by CCR. Here, we present a method to relieve the inhibitory effect
      of CCR and allow simultaneous utilization of the lignocellulosic sugars of
      glucose and xylose by C. acetobutylicum. First, we utilized an in vivo gene
      reporter assay to demonstrate that an identified 14-nucleotide catabolite
      responsive element (CRE) sequence was sufficient to introduce CCR-mediated
      transcriptional inhibition, while subsequent mutation of the CRE sequence
      relieved the inhibitory effect. Next, we demonstrated that C. acetobutylicum
      harboring a CRE-less plasmid-borne xylose and pentose phosphate pathway operon
      afforded a 7.5-fold increase in xylose utilization in the presence of glucose as
      compared to a wild-type CRE plasmid-borne operon, effectively overcoming native
      CCR effects. The methodology presented here should translate to other members of
      Clostridium that exhibit CCR to enable simultaneous utilization of a vast array
      of carbon sources. 

PMID- 25981996
TI  - Bacterial community diversity in municipal waste landfill sites.
AB  - Little is known about the bacterial diversity of landfills and how environmental
      factors impact the diversity. In this study, PCR-based 454 pyrosequencing was
      used to investigate the bacterial communities of ten landfill leachate samples
      from five landfill sites in China. A total of 137 K useable sequences from the V3
      V6 regions of the 16S rRNA gene were retrieved from 205 K reads. These sequences
      revealed the presence of a large number of operational taxonomic units (OTUs) in
      the landfills (709-1599 OTUs per sample). The most predominant bacterial
      representatives in the landfills investigated, regardless of geographic area,
      included Gammaproteobacteria, Firmicutes, and Bacteroidetes. The phyla
      Fusobacteria and Tenericutes were also found for the first time to be predominant
      in the landfills. The phylum Fusobacteria predominated (51.5 and 48.8%) in two
      semi-arid landfills, and the phylum Tenericutes dominated (30.6%) at one humid,
      subtropical landfill. Further, a large number of Pseudomonas was detected in most
      samples, comprising the dominant group and accounting for 40.9 to 92.4% of the
      total abundance. Principal component analysis (PCA) and cluster analysis based on
      OTU abundance showed that the abundant taxa separated the bacterial community.
      Canonical correlation analysis (CCA) suggested that precipitation and landfilling
      age significantly impact on the bacterial community structure. The bacterial
      community function (e.g., cellulolytic bacteria, sulfate-reducing bacteria (SRB),
      sulfate-oxidizing bacteria, and xenobiotic organic compound (XOC)-degrading
      bacteria) was also diverse, but the pattern is unclear.

PMID- 25981997
TI  - Effects of beta-cyclodextrin and methyl jasmonate on the production of vindoline,
      catharanthine, and ajmalicine in Catharanthus roseus cambial meristematic cell
      cultures.
AB  - Long-term stable cell growth and production of vindoline, catharanthine, and
      ajmalicine of cambial meristematic cells (CMCs) from Catharanthus roseus were
      observed after 2 years of culture. C. roseus CMCs were treated with beta
      cyclodextrin (beta-CD) and methyl jasmonate (MeJA) individually or in combination
      and were cultured both in conventional Erlenmeyer flasks (100, 250, and 500 mL)
      and in a 5-L stirred hybrid airlift bioreactor. CMCs of C. roseus cultured in the
      bioreactor showed higher yields of vindoline, catharanthine, and ajmalicine than
      those cultured in flasks. CMCs of C. roseus cultured in the bioreactor and
      treated with 10 mM beta-CD and 150 MUM MeJA gave the highest yields of vindoline
      (7.45 mg/L), catharanthine (1.76 mg/L), and ajmalicine (58.98 mg/L),
      concentrations that were 799, 654, and 426 % higher, respectively, than yields of
      CMCs cultured in 100-mL flasks without elicitors. Quantitative reverse
      transcription (RT)-PCR showed that beta-CD and MeJA upregulated transcription
      levels of genes related to the biosynthesis of terpenoid indole alkaloids (TIAs).
      This is the first study to report that beta-CD induced the generation of NO,
      which plays an important role in mediating the production of TIAs in C. roseus
      CMCs. These results suggest that beta-CD and MeJA can enhance the production of
      TIAs in CMCs of C. roseus, and thus, CMCs of C. roseus have significant potential
      to be an industrial platform for production of bioactive alkaloids.

PMID- 25981998
TI  - Distribution and population structure characteristics of microorganisms in urban
      sewage system.
AB  - The sewage system functions as an important public infrastructure. The survived
      microbial population inside the sewage system plays an important role in the
      biochemical process during wastewater transportation within the system. The study
      aims to investigate the microbial communities spatial distribution inside
      manholes and sewage pipes by using the massive parallel 454 pyrosequencing
      combined with denaturing gradient gel electrophoresis of V1-V3 regions of 16S
      rRNA. The microbial structure, distribution characteristic, taxonomic composition
      analysis, and compositional overlaps of the microbial community both were
      conducted. The result indicated that the changes in microbial diversity exhibited
      a consistent trend with average dehydrogenase activity. Proteobacteria,
      Firmicutes, and Anaerolineae were the dominant bacteria in the sewage system. The
      microbial community exhibited distinguishing characteristics in comparison with
      fecal, surface water, and wastewater treatment process. Parachlamydia
      acanthamoebae, Zymophilus paucivorans, and uncultured Epsilon proteobacterium
      were mainly found at the upper position of the manhole, while Microbacterium sp.
      was mainly found at the lower position. Longilinea, Georgenia, and Desulforhabdus
      were mainly observed in the sewage pipe. The microbial bacteria that survived in
      the anaerobic environment (i.e., sulfate reduction bacteria groups) exhibited a
      significant positive relationship with anaerobic crucial environmental factors in
      the redundancy analysis. 

PMID- 25981999
TI  - A novel method to produce armored double-stranded DNA by encapsulation of MS2
      viral capsids.
AB  - With the rapid development of molecular diagnostic techniques, there is a growing
      need for quality controls and standards with favorable properties to monitor the
      entire detection process. In this study, we describe a novel method to produce
      armored hepatitis B virus (HBV) and human papillomavirus (HPV) DNA for use in
      nucleic acid tests, which was confirmed to be stable, homogeneous, noninfectious,
      nuclease resistant, and safe for shipping. We demonstrated that MS2 bacteriophage
      could successfully package double-stranded DNA of 1.3-, 3-, 3.5-, and 6.5-kb
      length into viral capsids with high reassembly efficiency. This is the first
      application of RNA bacteriophage MS2 as a platform to encapsulate double-stranded
      DNA, forming virus-like particles (VLPs) which were indistinguishable from native
      MS2 capsids in size and morphology. Moreover, by analyzing the interaction
      mechanism of pac site and the MS2 coat protein (CP), we found that in addition to
      the recognized initiation signal TR-RNA, TR-DNA can also trigger spontaneous
      reassembly of CP dimers, providing a more convenient and feasible method of
      assembly. In conclusion, this straightforward and reliable manufacturing approach
      makes armored DNA an ideal control and standard for use in clinical laboratory
      tests and diagnostics, possessing prospects for broad application, especially
      providing a new platform for the production of quality controls for DNA viruses. 

PMID- 25982000
TI  - Both BAT1 and ARO8 are responsible for unpleasant odor generation in halo
      tolerant yeast Zygosaccharomyces rouxii.
AB  - Soy sauce yeast Zygosaccharomyces rouxii plays a central role in the production
      of flavor compounds in soy sauce, while the flor-forming strain spoils its
      quality by producing 2-methylpropanoic acid, 2-methylbutanoic acid, and 3
      methylbutanoic acid, which have an unpleasant odor. To investigate the
      relationship between flor formation and unpleasant odor, we measured the volatile
      compounds that accumulated under various growth conditions. As a result, marked
      amounts of 2-methylpropanoic acid, 2-methylbutanoic acid, or 3-methylbutanoic
      acid accumulated in synthetic medium containing valine, isoleucine, or leucine,
      respectively, under aerobic growth conditions. These results implied that the
      unpleasant compounds were produced from their corresponding branched chain amino
      acid (BCAA) when the cell was placed under aerobic condition through flor
      formation. The first step in BCAA catabolism and the last step in BCAA anabolism
      are both catalyzed by a BCAA transaminase. A mutant lacking the BCAA transaminase
      gene, BAT1, resulted in valine and isoleucine auxotrophy, while a mutant lacking
      both BAT1 and the alpha-aminoadipate aminotransferase gene, ARO8, resulted in
      valine, isoleucine, and leucine auxotrophy. Although the bat1? aro8? double
      mutant formed flor similarly to the wild-type strain, the mutant exhibited less
      unpleasant odor generation. These results suggest that the interconversion
      between 4-methyl-2-oxopentanoate and leucine is catalyzed by both Bat1p and Aro8p
      in Z. rouxii. Taken together, these results indicate that flor formation is not
      seemed to be directly linked to unpleasant odor generation. These findings
      encourage us to breed flor-forming yeasts without an unpleasant odor. 

PMID- 25982001
TI  - Biopolymers for sample collection, protection, and preservation.
AB  - One of the principal challenges in the collection of biological samples from air,
      water, and soil matrices is that the target agents are not stable enough to be
      transferred from the collection point to the laboratory of choice without
      experiencing significant degradation and loss of viability. At present, there is
      no method to transport biological samples over considerable distances safely,
      efficiently, and cost-effectively without the use of ice or refrigeration.
      Current techniques of protection and preservation of biological materials have
      serious drawbacks. Many known techniques of preservation cause structural
      damages, so that biological materials lose their structural integrity and
      viability. We review applications of a novel bacterial preservation process,
      which is nontoxic and water soluble and allows for the storage of samples without
      refrigeration. The method is capable of protecting the biological sample from the
      effects of environment for extended periods of time and then allows for the easy
      release of these collected biological materials from the protective medium
      without structural or DNA damage. Strategies for sample collection, preservation,
      and shipment of bacterial, viral samples are described. The water-soluble polymer
      is used to immobilize the biological material by replacing the water molecules
      within the sample with molecules of the biopolymer. The cured polymer results in
      a solid protective film that is stable to many organic solvents, but quickly
      removed by the application of the water-based solution. The process of
      immobilization does not require the use of any additives, accelerators, or
      plastifiers and does not involve high temperature or radiation to promote
      polymerization. 

PMID- 25982002
TI  - Increased short-range and long-range functional connectivity in first-episode,
      medication-naive schizophrenia at rest.
AB  - OBJECTIVE: Schizophrenia is conceived as a disconnection syndrome and anatomical
      distance may affect functional connectivity (FC) in schizophrenia patients.
      However, whether and how anatomical distance affects FC remains unclear in first
      episode, medication-naive schizophrenia at rest. METHODS: Forty-nine
      schizophrenia patients and 50 age-, sex-, and education-matched healthy controls
      underwent resting-state functional magnetic resonance imaging scanning. Regional
      FC strength was computed for each voxel in the brain, which was further divided
      into short-range and long-range FC strength. RESULTS: The patients exhibited
      increased short-range positive FC strength in the left superior medial frontal
      gyrus, and increased long-range positive FC strength in the right angular gyrus
      and bilateral posterior cingulate cortex (PCC)/precuneus compared with the
      controls. Further seed-based FC analysis showed that the left superior medial
      frontal gyrus had increased short-range FC with the right inferior frontal gyrus,
      while the right angular gyrus and bilateral PCC/precuneus had increased long
      range FC with the prefrontal gyrus. No significant correlation was observed
      between abnormal FC strength and clinical variables in the patient group.
      CONCLUSIONS: The findings reveal a pattern of increased anatomical distance
      affecting FC in the patients, with the results of increased short-range positive
      FC strength in the anterior default-mode network (DMN) and increased long-range
      positive FC strength in the posterior DMN in schizophrenia, and highlight the
      importance of the DMN in the neurobiology of schizophrenia.

PMID- 25982003
TI  - Polyphosphate: A Morphogenetically Active Implant Material Serving as Metabolic
      Fuel for Bone Regeneration.
AB  - The initial mineralization centers during human bone formation onto osteoblasts
      are composed of CaCO3 . Those bioseeds are enzymatically formed via carbonic
      anhydrase(s) in close association with the cell surface of the osteoblasts.
      Subsequently, the bicarbonate/carbonate anions are exchanged non-enzymatically by
      inorganic phosphate [Pi ]. One source for the supply of Pi is polyphosphate
      [polyP] which is a physiological polymer, formed in the osteoblasts as well as in
      the platelets. The energy-rich acid anhydride bonds within the polyP chain are
      cleaved by phosphatase(s); during this reaction free-energy might be released
      that could be re-used, as metabolic fuel, for the maintenance of the steady-state
      concentrations of the substrates/products during mineralization. Finally it is
      outlined that polyP, as a morphogenetically active scaffold, is even suitable for
      3D cell printing. 

PMID- 25982004
TI  - Magnesium Status and Its Relationship with C-Reactive Protein in Obese Women.
AB  - This study assessed the relationship between magnesium status and C-reactive
      protein concentration in obese and nonobese women. This cross-sectional study
      included 131 women, aged between 20 and 50 years, who were divided into two
      groups: obese (n=65) and control (n=66) groups. Magnesium intake was monitored
      using 3-day food records and NutWin software version 1.5. The plasma,
      erythrocyte, and urinary magnesium concentrations were determined by flame atomic
      absorption spectrophotometry. C-reactive protein concentration in serum was
      measured by immunoturbidimetric assay. The mean values of the magnesium content
      in the diet were lower than those recommended, though there was no significant
      difference between groups (p>0.05). The mean concentrations of plasma and
      erythrocyte magnesium were within the normal range, with no significant
      difference between groups (p>0.05). Urinary excretion of this mineral was less
      than the reference values in both groups, with no significant difference
      (p>0.05). The mean concentration of serum C-reactive protein was within the
      normal range in both groups, with no significant difference (p>0.05). There was a
      positive correlation between urinary magnesium and serum C-reactive protein
      (p=0.015). Obese patients ingest low dietary magnesium content, which seems to
      induce hypomagnesuria as a compensatory mechanism to keep plasma concentrations
      of the mineral at adequate levels. The study shows a positive correlation between
      urinary magnesium concentrations and serum C-reactive protein, suggesting the
      influence of hypomagnesuria on this inflammatory protein in obese women.

PMID- 25982005
TI  - Effect of rural practice observation on the anxiety of medical students.
AB  - INTRODUCTION: The aim of this study is to identify the level and causes of
      anxiety of sixth year medical students related to working in a rural area and the
      effect of a 1-day mobile rural health service observation on their anxiety.
      METHODS: In the Ondokuz Mayis University Medical School in Samsun, Turkey, 212
      students participated in a 1-day mobile rural health service led by a family
      physician. Between June 2011 and June 2013, during their family medicine
      internship, each student completed a structured questionnaire and a State-Trait
      Anxiety Inventory (STAI) before and after the observation. RESULTS: A total of
      85.8% of the students preferred to work in an urban area compared to 14.2%, who
      preferred a rural area. Currently, 89.6% of the students live in an urban area
      while 84.4% had lived in an urban area during most of their childhood. A total of
      18.5% had no opinion about living conditions in a rural area, 71.7% thought they
      would be able to deal with the challenges, and 52.4% said the idea of working in
      a rural area made them anxious. Those students who had lived in a rural area as a
      child were found to be less anxious about working in a rural area. The
      association between the preferred work area and the student's anxiety about
      working in a rural area was statistically significant (<i>p</i><0.001). Of the
      students, 76.8% thought that rural areas are more difficult places to work; a
      major reason for this as stated by 76.4% was the desire to have access to easy
      transportation. Difficult living conditions was noted by the students as their
      main reason for not wanting to work in a rural areas. Of the students, 77.8%
      answered that the 1-day rural health service observation positively affected
      their perspective on working in a rural area. There were 102 (48.1%) anxious
      students before the observation and the total decreased to 87 (41%) after the
      observation. CONCLUSIONS: Difficult living conditions were the main reason for
      students' anxiety about working in a rural area. Most of the students answered
      that the curriculum positively affected their perspective. Medical schools should
      provide students with the rural primary care environment experience, which would
      decrease their anxiety.

PMID- 25982006
TI  - Alexithymia level and response to computer-based training in cognitive behavioral
      therapy among cocaine-dependent methadone maintained individuals.
AB  - BACKGROUND: Alexithymia, a characteristic marked by poor ability to identify,
      define and communicate emotions, has been associated with poorer treatment
      outcome, including traditional clinician delivered CBT. Computerized cognitive
      behavioral therapy (CBT4CBT), an effective adjunct to treatment, may provide a
      means of conveying skills without requiring interaction with a clinician.
      METHODS: Seventy-three methadone maintained, cocaine dependent individuals
      participating in an 8-week randomized clinical trial comparing standard methadone
      maintenance to methadone maintenance plus CBT4CBT completed the Toronto
      Alexithymia Scale (TAS-20) at pretreatment, post-treatment, and follow-ups
      conducted one, two, and 6 months after treatment. RESULTS: There were no
      statistically significant differences on baseline TAS-20 scores by multiple
      demographic and substance use variables including gender and substance use
      severity. Higher TAS-20 scores were associated with somewhat higher levels of
      distress as measured by the Beck Depression Inventory and multiple Brief Severity
      Index scales. TAS-20 scores remained relatively stable throughout the duration of
      treatment and follow-up. Indicators of treatment process, including treatment
      retention, adherence and therapeutic alliance, were not significantly correlated
      with TAS-20 scores. There was a significant interaction of alexithymia and
      treatment condition, such that individuals with higher baseline scores on the TAS
      20 submitted significantly higher percentages of cocaine-negative urine
      toxicology specimens and reported a higher percentage of abstinence days, and
      longer periods of consecutive abstinence within treatment when assigned to
      CBT4CBT compared with treatment as usual. CONCLUSIONS: These findings suggest
      that individuals with increased alexithymia may benefit from computerized CBT;
      possibly via reduced demands on interpersonal skills and interactions associated
      with computerized therapies.

PMID- 25982007
TI  - Clinician-delivered contingency management increases engagement and attendance in
      drug and alcohol treatment.
AB  - OBJECTIVE: This study examined the impact of a low-cost contingency management
      (CM) delivered by program clinicians on treatment attendance and utilization for
      patients enrolled in outpatient psychosocial substance abuse treatment. METHODS:
      The study used a pre-posttest design to compare substance abuse patients who
      received Reinforcement-Based Treatment (RBT) plus low cost CM (n=130; RBT+CM) to
      patients who received RBT only (n=132, RBT). RBT+CM participants received a $10
      incentive for returning to treatment the day following intake assessment (day
      one), and a $15 incentive for attending treatment on day five following
      admission. RBT clients received standard care intervention without the addition
      of the CM procedures. Groups were compared on proportion of participants who
      returned to treatment on day one, mean days of treatment attendance, individual
      sessions attended, and treatment utilization during the first week and the first
      month following treatment admission. RESULTS: Both the RBT+CM and RBT group
      participants returned to the clinic on day one at high rates (95% versus 89%,
      respectively). However, the RBT group participants were more likely to attend the
      intake assessment only (i.e., never return to treatment) compared to the RBT+CM
      participants. Additionally, the RBT+CM participants attended significantly more
      treatment days, attended more individual counseling sessions, and had higher
      rates of overall treatment utilization compared to the RBT participants during
      the one week and one month following treatment admission. CONCLUSIONS: Findings
      support the feasibility and effectiveness of a CM intervention delivered by
      clinicians for increasing treatment attendance and utilization in a community
      substance abuse program.

PMID- 25982008
TI  - The association between the duration of postoperative acute kidney injury and in
      hospital mortality in critically ill patients after non-cardiac surgery: an
      observational cohort study.
AB  - OBJECTIVES: The severity of acute kidney injury (AKI) has been a well-known
      predictor for in-hospital mortality. Whether AKI duration could predict in
      hospital mortality is not clear. This study determines the association between
      the in-hospital mortality and AKI duration in patients after non-cardiac surgery.
      MATERIALS AND METHODS: Surgical patients who were admitted to the ICU were
      enrolled. AKI cases were defined using KDIGO guidelines and categorized according
      to the tertiles of AKI duration (1st tertile: 2 days, 2nd tertile: 3-6 days and
      3rd tertile: 7 days). The adjusted hazard ratios (HRs) for in-hospital mortality
      are compared to those without AKI. The predictability of mortality is accessed by
      calculating the area under the curve (AUC) for the receiver operating
      characteristic (ROC) curve. RESULTS: From a total of 318 postoperative patients,
      98 developed AKI (1st tertile: 34 cases, 2nd tertile: 30 cases and 3rd tertile:
      34 cases) and 220 had no AKI. The in-hospital mortality rates are 6.8% (non-AKI),
      50% (1st tertile), 46.7% (2nd tertile) and 47% (3rd tertile). The HR's for in
      hospital mortality are 7.92, 6.68 and 1.68, compared to the non-AKI group (p =
      0.006, 0.021 and 0.476). Cumulative in-hospital survival rates are significantly
      different for the non-AKI group and the AKI groups (p < 0.001). The AUC for AKI
      duration and stage together (0.804) is higher than that for AKI stage and AKI
      duration alone (0.803 and 0.777) (both ps < 0.001). CONCLUSION: In addition to
      severity, the duration of AKI may be a predictor of in-hospital mortality in
      patients, after non-cardiac surgery.

PMID- 25982009
TI  - Mixed mucoepidermoid carcinoma and adenocarcinoma of the lung: Two cases with
      unusual histologic features.
AB  - We herein report two cases of non-small cell lung cancer with unusual histologic
      patterns, comprising mixed mucoepidermoid carcinoma and adenocarcinoma. Both
      cases presented identical genetic mutations in each histologic component of the
      tumor; specifically, one case possessed an ALK-rearrangement and the other case
      presented a deletion in exon 19 of the EGFR gene. The two current cases, as well
      as an additional case that we previously reported, were all identified as being a
      specific type of mixed lung cancer with driver mutations typically encountered in
      conventional lung adenocarcinomas. Our findings support the supposition that
      different histological components in mixed-histology lung cancer are clonally
      related. Accordingly, extensive tissue sampling is necessary to avoid overlooking
      minor adenocarcinomatous components, as patients with mixed lung cancer could
      potentially benefit from treatment with tyrosine kinase inhibitors. 

PMID- 25982010
TI  - Platinum derivatives alone, a reasonable option to treat locally advanced non
      small cell lung cancer with chemo-radiotherapy.

PMID- 25982011
TI  - Is the current diagnostic algorithm reliable for selecting cases for EGFR- and
      KRAS-mutation analysis in lung cancer?
AB  - OBJECTIVES: Adenocarcinoma (ADC) of the lung may harbor EGFR- or KRAS-mutations,
      which are relevant for treatment decisions. There is no consensus on the
      percentages of EGFR- and KRAS-mutations that are allowed to be missed by a
      diagnostic algorithm, although a percentage of less than 1% for EGFR-mutations
      has been suggested. The current guidelines do not advise to perform EGFR-mutation
      analysis in unequivocal squamous cell carcinoma (SqCC). For KRAS-mutations no
      threshold for missing cases is suggested yet. To improve segregation between ADC
      and SqCC in small samples, the classification of lung cancer was updated in 2011,
      adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm.
      In this study we examined how many cases with an EGFR- or KRAS-mutation in our
      database would have been missed, if the current guideline for selecting cases for
      mutation analysis would have been applied. MATERIALS AND METHODS: From an
      institutional lung cancer database of specimens analyzed for EGFR- and KRAS
      mutations (n=816), cases harboring a mutation without being treated prior with an
      EGFR-TKI were selected (n=336). Corresponding original histological diagnoses and
      IHC for TTF-1, p63 and PAS-D were collected. Cases with SqCC on HE or with an IHC
      pattern favoring SqCC were reassessed according to the criteria of the 2011
      classification. RESULTS: From the 336 cases 70% had a KRAS-mutation and 30% an
      EGFR-mutation. The number of cases with SqCC on HE and/or an IHC-profile favoring
      SqCC was 12. After the reassessment six specimens (1.8%) would not have been
      tested for EGFR-/KRAS-mutations, if the current diagnostic algorithm had been
      used: 2.0% of EGFR-mutations and 1.7% KRAS-mutations. All six cases were NSCLC
      with an IHC-profile favoring SqCC. CONCLUSION: Most NSCLC-cases with EGFR- and
      KRAS-mutations are selected by the current diagnostic algorithm. As a small but
      relevant fraction is missed, there is room for improvement.

PMID- 25982013
TI  - Spatial illustration of health-care workforce accessibility index in China: How
      far has our 2009 health-care reform brought us?
AB  - OBJECTIVE: The objective of the study was to evaluate the effectiveness of
      China's health-care reform from 2009 to 2011 by examining China's annual health
      care workforce statistics of 2008 and 2011. DESIGN: The design of the study was a
      secondary data analysis. MAIN OUTCOME MEASURE: The main outcome measure used was
      the Primary Health Care Worker Accessibility Index (PHCWA). RESULTS: The
      statistics illustrated the impact health-care reform had on the provision of
      primary health care in rural areas. The results showed that the health-care
      reform of 2009 generally improved access to the primary health-care workforce in
      all 28 areas (range of increase: 13.18-324.0%). However, an increasing disparity
      in regional health care based on the increase of the standard deviations of PHCWA
      (range of increase: 36.44-77.10%) may be an issue that policy-makers and analysts
      will have to face. CONCLUSIONS: Concerted policy efforts from both the provincial
      and central governments are needed to narrow the gaps. Regional development
      should not only focus on the economic aspect, but also account for the fact that
      the adequate provision of primary health care is part of the infrastructure that
      makes development possible and sustainable.

PMID- 25982012
TI  - Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR
      inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with
      brain metastases.
AB  - In-frame fusion KIF5B (the-kinesin-family-5B-gene)-RET transcripts have been
      characterized in 1-2% of non-small cell lung cancers and are known oncogenic
      drivers. The RET tyrosine kinase inhibitor, vandetanib, suppresses fusion
      induced, anchorage-independent growth activity. In vitro studies have shown that
      vandetanib is a high-affinity substrate of breast cancer resistance protein
      (Bcrp1/Abcg2) but is not transported by P-glycoprotein (P-gp), limiting its blood
      brain barrier penetration. A co-administration strategy to enhance the brain
      accumulation of vandetanib by modulating P-gp/Abcb1- and Bcrp1/Abcg2-mediated
      efflux with mTOR inhibitors, specifically everolimus, was shown to increase the
      blood-brain barrier penetration. We report the first bench-to-bedside evidence
      that RET inhibitor combined with an mTOR inhibitor is active against brain
      metastatic RET-rearranged lung cancer and the first evidence of blood-brain
      barrier penetration. A 74-year-old female with progressive adenocarcinoma of the
      lung (wild-type EGFR and no ALK rearrangement) presented for therapy options. A
      deletion of 5'RET was revealed by FISH assay, indicating RET-gene rearrangement.
      Because of progressive disease in the brain, she was enrolled in a clinical trial
      with vandetanib and everolimus (NCT01582191). Comprehensive genomic profiling
      revealed fusion of KIF5B (the-kinesin-family-5B-gene) and RET, in addition to
      AKT2 gene amplification. After two cycles of therapy a repeat MRI brain showed a
      decrease in the intracranial disease burden and PET/CT showed systemic response
      as well. Interestingly, AKT2 amplification seen is a critical component of the
      PI3K/mTOR pathway, alterations of which has been associated with both de novo and
      acquired resistance to targeted therapy. The addition of everolimus may have both
      overcome the AKT2 amplification to produce a response in addition to its direct
      effects on the RET gene. Our case report forms the first evidence of blood-brain
      barrier penetration by vandetanib in combination with everolimus. Further
      research is required in this setting. 

PMID- 25982014
TI  - Full-Body MRI in Patients With an Implantable Cardioverter-Defibrillator: Primary
      Results of a Randomized Study.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of patients with conventional
      implantable cardioverter-defibrillators (ICD) is contraindicated. OBJECTIVES:
      This multicenter, randomized trial evaluated safety and efficacy of a novel ICD
      system specially designed for full-body MRI without restrictions on heart rate or
      pacing dependency. The primary safety objective was >90% freedom from MRI-related
      events composite endpoint within 30 days post-MRI. The primary efficacy endpoints
      were ventricular pacing capture threshold and ventricular sensing amplitude.
      METHODS: Subjects received either a single- or dual-chamber ICD. In a 2:1
      randomization, subjects either underwent MRI at 1.5-T of the chest, cervical, and
      head regions to maximize radiofrequency exposure up to 2 W/kg specific absorption
      rate and gradient field exposure to 200 T/m/s per axis (MRI group, n = 175), or
      they underwent a 1-h waiting period without MRI (control group, n = 88). A subset
      of MRI patients underwent ventricular fibrillation induction testing post-MRI to
      characterize defibrillation function. RESULTS: In 42 centers, 275 patients were
      enrolled (76% male, age 60.4 +/- 13.8 years). The safety endpoint was met with
      100% freedom from the composite endpoint (p < 0.0001). Both efficacy endpoints
      were met with minimal differences in the proportion of MRI and control patients
      who demonstrated a <=0.5 V increase in ventricular pacing capture threshold (100%
      MRI vs. 98.8% control, noninferiority p < 0.0001) or a <=50% decrease in R-wave
      amplitude (99.3% MRI vs. 98.8% control, noninferiority p = 0.0001). A total of 34
      ventricular tachyarrhythmia/ventricular fibrillation episodes (20 induced; 14
      spontaneous) occurred in 24 subjects post-MRI, with no observed effect on
      sensing, detection, or treatment. CONCLUSIONS: This is the first randomized
      clinical study of an ICD system designed for full-body MRI at 1.5-T. These data
      support that the system is safe and the MRI scan does not adversely affect
      electrical performance or efficacy. (Confirmatory Clinical Trial of the Evera MRI
      System for Conditionally-Safe MRI Access; NCT02117414).

PMID- 25982015
TI  - Safe MRI in Patients With an Upgraded (Conditional) Implantable Cardioverter
      Defibrillator: The Beneficial Tip of a Troublesome Iceberg.

PMID- 25982016
TI  - Frailty in advanced heart failure: a systematic review.
AB  - Frailty is a common geriatric syndrome of increased vulnerability to adverse
      events. The prevalence of frailty among chronic heart failure (CHF) is high and
      confers a greater risk of adverse events including falls, hospitalisation and
      mortality. There have been few studies assessing frailty in CHF. A review of the
      key databases was conducted from 2004 to 2014 including the key search terms
      'frail elderly' and 'heart failure'. The following electronic databases were
      searched: Medline, Cumulative Index for Nursing and Allied Health and Academic
      Search Complete, with reference lists being manually searched. Articles were
      included if frailty was assessed using a valid measuring tool in a population
      with a confirmed diagnosis of CHF. The search yielded a total of 393 articles
      with 8 articles being selected for review. The prevalence of frailty among those
      with CHF was high, ranging from 18 to 54 %. The frailty phenotype and geriatric
      assessments tools were the most common frailty measures utilised; high rates of
      co-morbidity, hospitalisation and mortality were identified. Frailty is common in
      CHF and is associated with adverse outcomes. 

PMID- 25982017
TI  - Investigating failure behavior and origins under supposed "shear bond" loading.
AB  - PURPOSE: This study evaluated failure behavior when resin-composite cylinders
      bonded to dentin fractured under traditional "shear" testing. Failure was
      assessed by scaling of failure loads to changes in cylinder radii and fracture
      surface analysis. Three stress models were examined including failure by: bonded
      area; flat-on-cylinder contact; and, uniformly-loaded, cantilevered-beam.
      METHODS: Nine 2-mm dentin occlusal dentin discs for each radii tested were
      embedded in resin and bonded to resin-composite cylinders; radii (mm)=0.79375;
      1.5875; 2.38125; 3.175. Samples were "shear" tested at 1.0mm/min. Following
      testing, disks were finished with silicone carbide paper (240-600grit) to remove
      residual composite debris and tested again using different radii. Failure
      stresses were calculated for: "shear"; flat-on-cylinder contact; and, bending of
      a uniformly-loaded cantilevered beam. Stress equations and constants were
      evaluated for each model. Fracture-surface analysis was performed. RESULTS:
      Failure stresses calculated as flat-on-cylinder contact scaled best with its
      radii relationship. Stress equation constants were constant for failure from the
      outside surface of the loaded cylinders and not with the bonded surface area or
      cantilevered beam. Contact failure stresses were constant over all specimen
      sizes. Fractography reinforced that failures originated from loaded cylinder
      surface and were unrelated to the bonded surface area. CONCLUSIONS: "Shear bond"
      testing does not appear to test the bonded interface. Load/area "stress"
      calculations have no physical meaning. While failure is related to contact
      stresses, the mechanism(s) likely involve non-linear damage accumulation, which
      may only indirectly be influenced by the interface.

PMID- 25982018
TI  - Effect of different enamel matrix derivative proteins on behavior and
      differentiation of endothelial cells.
AB  - OBJECTIVES: Enamel matrix derivative (EMD) is an effective biomaterial for
      periodontal tissue regeneration and might stimulate angiogenesis. In order to
      clarify mechanisms underlying its biological activity, we separated two EMD
      fractions with different molecular weight protein components and investigated
      their effects on human umbilical vein endothelial cells (HUVECs) in vitro.
      METHODS: Fraction Low-Molecular Weight (LMW) included proteins with a molecular
      weight (M.W.)<8kDa. Fraction LMW-depleted included proteins with M.W.>8kDa and
      lower than approximately 55kDa. The effect of EMD fractions on
      proliferation/viability, apoptosis, migration and expression of angiopoetin-2
      (ang-2), von Willebrand factor (vWF), E-selectin, intracellular adhesion
      molecules 1 (ICAM-1), vascular endothelial growth factor (VEGF) receptors Flt-1
      and KDR was investigated. RESULTS: The proliferation/viability of HUVECs was
      inhibited by both LMW and LMW-depleted at concentrations 100MUg/ml, whereas EMD
      slightly increased cell proliferation/viability. The expression of all
      investigated proteins was up-regulated by EMD. However, differences in the effect
      of EMD fractions on the protein expression were observed. The effect of LMW
      depleted on the expression of ICAM-1 and E-selectin was markedly higher compared
      to LMW. In contrast, the expression of vWF and VEGF receptors Flt-1 and KDR was
      primarily affected LMW than by LMW depleted. The expression of ang-2 was not
      influenced by LMW and LMW-depleted. HUVECs migration was stimulated more strongly
      by LMW than by EMD and LMW-depleted. CONCLUSION: Our in vitro study shows that
      the proteins composing EMD have different and specific biological activities and
      consequently have the ability to cover different aspects of EMD's biological and
      clinical effects.

PMID- 25982019
TI  - Clinical pathway for early discharge after complete primary repair of exstrophy
      and epispadias by using a spica cast.
AB  - INTRODUCTION/OBJECTIVE: Secure closure of the pubic diastasis during bladder
      exstrophy and epispadias repair decreases the abdominal wall tension at the time
      of reconstruction. Pelvic osteotomies are routinely performed at the time of
      abdominal wall and bladder reconstruction in order to more easily facilitate
      pubic symphyseal diastasis approximation. Postoperative pelvic immobilization is
      performed by methods that include modified Buck's traction, modified Bryant's
      traction, and spica casting. People undergoing closure often require inpatient
      hospitalization for 2-8 weeks because of the pelvic immobilization. The present
      study examined the findings from a clinical pathway for early discharge after
      complete primary repair of exstrophy (CPRE) and proximal epispadias repair with
      spica casting. METHODS: The present study is a retrospective review of patients
      that underwent pelvic osteotomies with spica casting at the time of CPRE or
      proximal epispadias repair from November 2006 to March 2013. All patients had
      anterior innominate osteotomies and spica cast pelvic immobilization. RESULTS:
      Pelvic osteotomies and spica cast pelvic immobilization were performed on 17
      children. The median postoperative stay was 6.0 days and the subdivided results
      are in Table. No children experienced an abdominal or orthopedic complication. A
      few children required minor cast adjustments to relieve pressure. After cast
      removal, no skin breakdown, pressure necrosis, or nerve palsy were found. The
      median length of casting without pinning was 31 (26-48) days. DISCUSSION: The use
      of spica cast pelvic immobilization after exstrophy and epispadias repair is safe
      and allows for earlier discharge when compared to other methods of pelvic
      immobilization. However, although the family appreciates early discharge and
      additional bonding, the priority is the success of the closure. The present
      findings demonstrate, and are corroborated by other spica cast publications, that
      spica casting is as effective as modified Bryant's traction or modified Buck's
      traction. The success rates for CPRE with spica casting are similar to published
      staged repairs and have the benefit of allowing for bladder cycling, which
      potentially enables better bladder growth and development. If success and
      complication rates are comparable amongst the different pelvic immobilization
      groups, then variables including hospital length of stay and cost become
      appropriate comparisons. CONCLUSION: The shortened discharge time, along with a
      significant decrease in acuity of care leads to significant decreases in hospital
      costs. Additional hospital stay when using modified Bryant's traction or modified
      Buck's traction with external fixation will accrue significant hospital costs.

PMID- 25982020
TI  - Inflammatory myofibroblastic tumour of the bladder in children: a review.
AB  - INTRODUCTION: Inflammatory myofibroblastic tumours of the bladder (IMTB) are
      rare, and feature a benign and reactive proliferation of myofibroblasts. 25% of
      the reported IMTB cases in the literature occur in children. The present study
      presents a review of IMTB in children. DISCUSSION: The data from 42 reported
      cases of paediatric IMTB in the world literature are summarised, including two
      recent cases from the present centre. Paediatric IMTB equally affects males and
      females. It mainly presents with haematuria, dysuria or abdominal pain. Lesions
      can vary in size, but mean size is 5.5 cm. Mean age is 7.5 years. The aetiology
      of IMTB is poorly understood, but includes infective or traumatic aetiologies, or
      a possible clonal lesion. IMTB may specifically show clonal gene rearrangements
      involving the anaplastic lymphoma kinase (ALK-1) gene. To differentiate IMTB from
      rhabdomyosarcoma, tissue diagnosis and careful histological analysis are
      essential. Tumour biopsy can be achieved by a transurethral approach or a
      transcutaneous approach with ultrasound guidance. Between 35 and 89% of cases of
      IMTB express ALK-1 by immunohistochemistry. ALK-1 expression is much less common
      in other bladder soft tissue tumours. ALK-1 is thus useful in the diagnosis of
      IMTB. The treatment of choice for IMTB is complete surgical resection of the
      lesion. In children, no proven recurrent or metastatic IMTB episodes are reported
      after excision. However IMTB recurrences are reported in adults, likely due to
      incomplete excision. Follow-up after excision is therefore recommended.
      CONCLUSIONS: Paediatric IMTB is uncommon. Tissue biopsy is essential for
      diagnosis. Careful histological assessment is required to differentiate IMTB from
      malignant paediatric bladder tumours such as rhabdomyosarcoma. ALK-1 expression
      is useful in confirming the diagnosis of IMTB. Treatment of choice is complete
      surgical resection of the lesion. Recurrence is reported in adult IMTB. Follow-up
      is therefore recommended.

PMID- 25982021
TI  - Do Vacuoles Obscure the Evidence for Auxin Homeostasis?

PMID- 25982022
TI  - The 5'-UTR intron of the midgut-specific BmAPN4 gene affects the level and
      location of expression in transgenic silkworms.
AB  - Introns are important for regulating gene expression. BmAPN4, which has a 5'-UTR
      upstream intron (5 UI), is specifically expressed in the entire silkworm midgut.
      In our previous study, the promoter region upstream of the 5 UI of BmAPN4 was
      cloned and identified as the P3 promoter (P3P) with activity only in the anterior
      midgut. In this study, the sequence consisting of the P3P and the 5 UI was cloned
      and named as P3P+5 UI. A transgenic vector was constructed in which EGFP was
      controlled by P3P+5 UI. Transgenic P3+5 UI silkworms were generated by embryo
      microinjection. RT-PCR showed P3P+5 UI activity throughout the larval stage.
      Intense green fluorescence was seen only in the entire midgut of P3+5 UI
      silkworms and expression was confirmed by RT-PCR. qPCR revealed that expression
      of EGFP in the anterior midgut of P3+5 UI silkworms was 64% higher than in P3
      silkworms, indicating the 5 UI sustained intron-mediated enhancement of gene
      expression. These results suggested that the BmAPN4 5 UI affected the level and
      site of expression. The 5 UI was cloned and added behind P2P, another specific
      promoter with activity only in the anterior midgut of silkworm, to construct the
      P2P+5 UI and transgenic P2+5 UI silkworms. Expression patterns were the same for
      P2P+5 UI and P2P, suggesting that the 5UI of BmAPN4 did not affect P2P. This
      study found that the BmAPN4 5 UI affected the amount and location of gene
      expression. Its influence appeared to be dependent on a specific promoter.

PMID- 25982023
TI  - The multi-tasking gut epithelium of insects.
AB  - The insect gut epithelium plays a vital role in multiple processes, including
      nutrition, immunity and osmoregulation. Recent research is revealing the
      molecular and biochemical basis of these functions. For example, the pattern of
      nutrient acquisition by the gut epithelium is integrated into the overall
      regulation of nutrient allocation, as illustrated by evidence for systemic
      controls over expression of key genes coding digestive enzymes and transporters
      in carbohydrate acquisition; and the abundance and diversity of microorganisms in
      the gut lumen is regulated by multiple molecular properties of the gut epithelial
      cells, including the synthesis of enzymes that produce reactive oxygen species
      and anti-microbial peptides. These traits are underpinned by the function of the
      gut epithelium as a selective barrier which mediates the controlled movement of
      water, ions, metabolites and macromolecules between the gut lumen and insect
      tissues. Breakdown of the gut epithelial barrier has been implicated in muscle
      paralysis of insects at low temperatures (chill coma) and in aging. The key
      challenge for future research is to understand how the multiple functions of the
      insect gut epithelium are integrated by signaling interactions among epithelial
      cells, the gut microbiota and other insect organs. 

PMID- 25982024
TI  - The clinical epidemiology and malignancies associated with Streptococcus bovis
      biotypes in 506 cases of bloodstream infections.
AB  - OBJECTIVES: To determine the incidence of Streptococcus bovis (Sb) biotypes
      causing bacteraemia and associated malignancies. METHODS: This is a retrospective
      analysis of patients with Sb bacteraemia, pulled out from a prospective
      surveillance protocol of bacteraemia cases, in three areas of Spain (1990-2013):
      a cattle area (Lugo), a fishing area (Ferrol) and an urban area (Barcelona).
      Colonoscopy and Sb biotypes (Sb-I and Sb-II) were determined in most cases.
      RESULTS: 506 patients with Sb bacteraemia; mean age 68.1 (+/-14.1) years, and
      66.2% were males. The cattle area, compared with the fishing and urban areas, had
      higher incidence of bacteraemia by SbI (40.29 vs 9.38 vs 6.15 cases/10(6) person
      years, P < 0.001) and bacteraemia by Sb-II (29.07 vs 9.84 vs 13.37 cases/10(6)
      person-years, P < 0.001). The Sb-I cases (n = 224), compared with Sb-II cases (n
      = 270), had greater rates of endocarditis (77.6% vs 9.6%, P < 0.001) and
      colorectal neoplasm (CRN) (50.9% vs 16.6%, P < 0.001), and smaller rates of
      biliary tract infection (2.2% vs 29.6%, P < 0.001) and non-colorectal malignancy
      (8.9% vs 31.4%, P < 0.001). CONCLUSION: There was a link between the cattle area
      and higher incidence of Sb bacteraemia. Sb-I differed from Sb-II cases in
      clinical findings and associated malignancies. Colonoscopy is mandatory in cases
      of endocarditis or bacteraemia caused by Sb-I.

PMID- 25982026
TI  - Twenty-one days of isolation: A prospective observational cohort study of an
      Ebola-exposed hot zone community in Liberia.
AB  - BACKGROUND: As West Africa continues to suffer from a deadly Ebola epidemic, the
      national health sectors struggle to minimize the damages and stop the spread of
      disease. METHODS: A cohort of inhabitants of a small village and an Ebola hot
      zone in Sinoe County of Liberia was followed on a day-by-day basis to search for
      new cases and to minimize the spread of Ebola to the other community members or
      to other regions. Technical, clinical, and humanistic aspects of the response are
      discussed in this report. RESULTS: Of the 22 confirmed Ebola cases in Sinoe
      County since the beginning of outbreak (June 16, 2014), 7 cases were inhabitants
      of Polay Town, a small village 5.5 miles east of Greenville, the Sinoe County
      capital. After the last wave of outbreak at the beginning of December, enhanced
      response activity provided essential coordination and mobilized the resources to
      stop the epidemic. Despite unprotected contacts in crowded houses, no new cases
      were detected among the contact families, or in the surrounding houses or
      communities. CONCLUSIONS: Strong national mobilization in a decentralized but
      harmonized system at the community level has been of great value in controlling
      the epidemic in Liberia. The major interventions include epidemiological
      surveillance, public information dissemination, effective communication, case
      management, and infection control.

PMID- 25982027
TI  - Retrospective detection of the hidden spread of OXA-48-producing Klebsiella
      pneumoniae in a French teaching hospital.

PMID- 25982028
TI  - Change in ocean subsurface environment to suppress tropical cyclone
      intensification under global warming.
AB  - Tropical cyclones (TCs) are hazardous natural disasters. Because TC
      intensification is significantly controlled by atmosphere and ocean environments,
      changes in these environments may cause changes in TC intensity. Changes in
      surface and subsurface ocean conditions can both influence a TC's
      intensification. Regarding global warming, minimal exploration of the subsurface
      ocean has been undertaken. Here we investigate future subsurface ocean
      environment changes projected by 22 state-of-the-art climate models and suggest a
      suppressive effect of subsurface oceans on the intensification of future TCs.
      Under global warming, the subsurface vertical temperature profile can be
      sharpened in important TC regions, which may contribute to a stronger ocean
      coupling (cooling) effect during the intensification of future TCs. Regarding a
      TC, future subsurface ocean environments may be more suppressive than the
      existing subsurface ocean environments. This suppressive effect is not spatially
      uniform and may be weak in certain local areas. 

PMID- 25982025
TI  - A novel meningococcal outer membrane vesicle vaccine with constitutive expression
      of FetA: A phase I clinical trial.
AB  - OBJECTIVES: Outer membrane vesicle (OMV) vaccines are used against outbreaks of
      capsular group B Neisseria meningitidis (MenB) caused by strains expressing
      particular PorA outer membrane proteins (OMPs). Ferric enterobactin receptor
      (FetA) is another variable OMP that induces type-specific bactericidal
      antibodies, and the combination of judiciously chosen PorA and FetA variants in
      vaccine formulations is a potential approach to broaden protection of such
      vaccines. METHODS: The OMV vaccine MenPF-1 was generated by genetically modifying
      N. meningitidis strain 44/76 to constitutively express FetA. Three doses of 25
      MUg or 50 MUg of MenPF-1 were delivered intra-muscularly to 52 healthy adults.
      RESULTS: MenPF-1 was safe and well tolerated. Immunogenicity was measured by
      serum bactericidal assay (SBA) against wild-type and isogenic mutant strains.
      After 3 doses, the proportion of volunteers with SBA titres >=1:4 (the putative
      protective titre) was 98% for the wild-type strain, and 77% for the strain 44/76
      FetA(on)PorA(off) compared to 51% in the strain 44/76 FetA(off)PorA(off),
      demonstrating that vaccination with MenPF-1 simultaneously induced FetA and PorA
      bactericidal antibodies. CONCLUSION: This study provides a proof-of-concept for
      generating bactericidal antibodies against FetA after OMV vaccination in humans.
      Prevalence-based choice of PorA and FetA types can be used to formulate a vaccine
      for broad protection against MenB disease.

PMID- 25982029
TI  - A component of the mitochondrial outer membrane proteome of T. brucei probably
      contains covalent bound fatty acids.
AB  - A subclass of eukaryotic proteins is subject to modification with fatty acids,
      the most common of which are palmitic and myristic acid. Protein acylation allows
      association with cellular membranes in the absence of transmembrane domains. Here
      we examine POMP39, a protein previously described to be present in the outer
      mitochondrial membrane proteome (POMP) of the protozoan parasite Trypanosoma
      brucei. POMP39 lacks canonical transmembrane domains, but is likely both
      myristoylated and palmitoylated on its N-terminus. Interestingly, the protein is
      also dually localized on the surface of the mitochondrion as well as in the
      flagellum of both insect-stage and the bloodstream form of the parasites. Upon
      abolishing of global protein acylation or mutation of the myristoylation site,
      POMP39 relocates to the cytosol. RNAi-mediated ablation of the protein neither
      causes a growth phenotype in insect-stage nor bloodstream form trypanosomes. 

PMID- 25982030
TI  - Zoonotic Enterocytozoon bieneusi genotypes in Pere David's deer (Elaphurus
      davidianus) in Henan, China.
AB  - Enterocytozoon bieneusi is a zoonotic pathogen of the phylum Microspora that
      infects humans as well as a variety of animal species worldwide. While molecular
      epidemiologic studies have characterized this parasite in various hosts, isolates
      from many susceptible hosts have not yet been examined. In this study, E.
      bieneusi was isolated from 47 Pere David's deer (Elaphurus davidianus) in Henan,
      China and characterized via PCR analysis of the internal transcribed spacer (ITS)
      gene. E. bieneusi was detected in 16 out of 47 (34.0%) fecal specimens examined.
      Sequence analysis of the ITS revealed six known genotypes: type IV (4), EbpC (4),
      EbpA (4), BEB6 (2), COS-I (1), and COS-II (1). Of these, type IV, EbpC, and EbpA
      are known to cause human microsporidiosis worldwide, whereas the remaining
      genotypes are generally specific to ruminants. The present study indicated that
      Pere David's deer are naturally infected with E. bieneusi, predominantly with
      zoonotic genotypes, and may pose a risk for human transmission. 

PMID- 25982032
TI  - Twice- rather than once-daily basal insulin is associated with better glycaemic
      control in Type 1 diabetes mellitus 12 months after skills-based structured
      education in insulin self-management.
AB  - AIM: This study investigates the relationship between basal insulin regimen and
      glycaemic outcomes 12 months after skills-based structured education in the UK
      Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.
      METHOD: Retrospective analysis of data from 892 DAFNE participants from 11 UK
      centres. RESULTS: Mean HbA1c 12 months after DAFNE was lower in those using twice
      rather than once-daily basal insulin after correcting for differences in
      baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1)
      mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7
      to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less
      good baseline control, HbA1c  >= 58 mmol/mol, who switched from once- to twice
      daily basal insulin. There was no difference in the 12-month HbA1c between users
      of glargine, detemir and NPH insulin after correcting for other variables.
      Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12
      months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23
      events/patient year in twice-daily basal insulin users. In the group with
      greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in
      twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88
      3.36, P = 0.110). CONCLUSION: After structured education in adults with Type 1
      diabetes mellitus, use of basal insulin twice rather than once daily was
      associated with lower HbA1c , independent of insulin type, with significant
      reductions in severe hypoglycaemia and ketoacidosis in all groups.

PMID- 25982031
TI  - A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial
      activity.
AB  - Malaria caused by the Plasmodium parasites continues to be an enormous global
      health problem owing to wide spread drug resistance of parasites to many of the
      available antimalarial drugs. Therefore, development of new classes of
      antimalarial agents is essential to effectively treat malaria. In this study, the
      efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic
      acid, and their synthetic derivatives was assessed for antimalarial activity.
      Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N
      benzyl derivatives showed excellent activity against P. falciparum parasites with
      IC50 values of 0.36 to 2.6 uM. Interestingly, N-dehydroabietylbenzamide showed
      potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100
      uM) to mammalian cells; thus, this compound can be an important antimalarial
      drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50
      value of ~82 uM. Several carboxylic group-derivatives of abietic acid were
      moderately active with IC50 values of ~8.2 to ~13.3 uM. These results suggest
      that a detailed understanding of the structure-activity relationship of abietane
      diterpenoids might provide strategies to exploit this class of compounds for
      malaria treatment.

PMID- 25982033
TI  - Optimization and planning of operating theatre activities: an original definition
      of pathways and process modeling.
AB  - BACKGROUND: The Operating Room (OR) is a key resource of all major hospitals, but
      it also accounts for up 40% of resource costs. Improving cost effectiveness,
      while maintaining a quality of care, is a universal objective. These goals imply
      an optimization of planning and a scheduling of the activities involved. This is
      highly challenging due to the inherent variable and unpredictable nature of
      surgery. METHODS: A Business Process Modeling Notation (BPMN 2.0) was used for
      the representation of the "OR Process" (being defined as the sequence of all of
      the elementary steps between "patient ready for surgery" to "patient operated
      upon") as a general pathway ("path"). The path was then both further standardized
      as much as possible and, at the same time, keeping all of the key-elements that
      would allow one to address or define the other steps of planning, and the
      inherent and wide variability in terms of patient specificity. The path was used
      to schedule OR activity, room-by-room, and day-by-day, feeding the process from a
      "waiting list database" and using a mathematical optimization model with the
      objective of ending up in an optimized planning. RESULTS: The OR process was
      defined with special attention paid to flows, timing and resource involvement.
      Standardization involved a dynamics operation and defined an expected operating
      time for each operation. The optimization model has been implemented and tested
      on real clinical data. The comparison of the results reported with the real data,
      shows that by using the optimization model, allows for the scheduling of about
      30% more patients than in actual practice, as well as to better exploit the OR
      efficiency, increasing the average operating room utilization rate up to 20%.
      CONCLUSIONS: The optimization of OR activity planning is essential in order to
      manage the hospital's waiting list. Optimal planning is facilitated by defining
      the operation as a standard pathway where all variables are taken into account.
      By allowing a precise scheduling, it feeds the process of planning and, further
      up-stream, the management of a waiting list in an interactive and bi-directional
      dynamic process.

PMID- 25982034
TI  - Chronic diseases, medical history and familial cancer, and risk of leukemia and
      non-Hodgkin's lymphoma in an adult population: a case-control study.
AB  - PURPOSE: This investigation was aimed at evaluating the association between
      chronic diseases, medical history and familial cancer, and the risk of developing
      hematological malignancies. METHODS: Data were drawn from a population-based case
      control study carried out to assess the risk of non-Hodgkin's lymphoma and
      leukemia in an adult population exposed to environmental air pollution in
      Northern Italy. Each case was classified according to the WHO ICD-O-3
      classification. Statistical analyses were performed by multivariable
      unconditional logistic regression in 573 interviewed subjects (199 lymphoid
      cases, 95 myeloid cases, and 279 healthy controls). RESULTS: Lymphoid
      malignancies were associated with a history of gastroduodenal ulcer (OR 2.1, 95 %
      CI 1.2-3.6), rheumatoid arthritis (OR 4.4, 95 % CI 1.3-19.0), anemia (OR 3.3, 95
      % CI 1.2-9.3), cholecystectomy (OR 2.9, 95 % CI 1.0-8.0), heavy diagnostic X-ray
      exposure (OR 2.1, 95 % CI 1.3-3.7), and a familial risk of non-Hodgkin's lymphoma
      (OR 10.1, 95 % CI 1.3-458). Myeloid malignancies were associated with non
      neoplastic thyroid diseases (OR 6.2, 95 % CI 1.7-35.6) and anemia (OR 6.8, 95 %
      CI 2.0-23.1). Subgroup analysis highlighted an excess risk of MALT in patients
      with gastroduodenal ulcer (OR 5.3, 95 % CI 1.04-23.7) and of AML in patients with
      rheumatoid arthritis (OR 6.9, 95 % CI 1.2-38.1), and of MDS in subjects exposed
      to heavy diagnostic X-ray (OR 3.4, 95 % CI 1.03-11.2) when the analysis was
      restricted to irradiation of pelvis, abdomen, or thorax. CONCLUSIONS: Most
      observed associations confirm results from previous studies. The higher risk of
      lymphoid malignancies among patients with a history of cholecystectomy needs
      further investigations.

PMID- 25982035
TI  - Involvement of G9A-like protein (GLP) in the development of mouse preimplantation
      embryos in vitro.
AB  - G9A-like protein (GLP) plays an important role in mouse early embryonic
      development. Glp-deficient embryos exhibit severe growth retardation and defects
      that lead to lethality at approximately Embryonic Day 9.5. In the present study
      we investigated the effect of microinjection of Glp-specific short interference
      (si) RNA into mouse zygotes on in vitro embryonic development. Knockdown of Glp
      induced abnormal embryonic development and reduced blastocyst formation.
      Expression of the pluripotency markers octamer-binding transcription factor 4
      (Oct4), SRY (sex determining region Y)-box 2 (Sox2) and Nanog was also
      significantly decreased in Glp-deficient embryos. The apoptotic index and
      expression of two pro-apoptotic genes, namely Caspase 3 and Caspase 9, were
      increased in Glp-deficient embryos. Moreover, methylation levels of dimethylated
      H3K9 (H3K9me2) were decreased in Glp-knockdown embryos. In conclusion, the
      results of the present study suggest that Glp deficiency suppresses H3K9me2
      modification and hinders mouse embryo development in vitro.

PMID- 25982036
TI  - A synopsis of drugs currently in preclinical and early clinical development for
      the treatment of benign prostatic hyperplasia.
AB  - INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common disease among men
      and significantly impacts quality of life by causing lower urinary tract symptoms
      (LUTS). Current medical therapies are not always adequate in controlling LUTS or
      slowing disease progression, and there is unmet need for new effective
      therapeutic options. AREAS COVERED: The authors review the standard current
      medical therapies for BPH which include the use of alpha-1 blockers, 5-alpha
      reductase inhibitors, combination therapy and PDE inhibitors. Following this, the
      authors then discuss new therapies that are currently undergoing preclinical and
      clinical investigation. EXPERT OPINION: Existing preclinical and clinical trials
      have highlighted many promising therapies to treat BPH. Further investigation
      with larger clinical trials is needed to establish these drugs as standard
      therapies. As the number of drugs in the arsenal against BPH continues to grow,
      providers and patients will have to engage in a discussion that weighs the risks
      and benefits of each therapy.

PMID- 25982037
TI  - Differences in nephrotoxicity risk and renal effects among anti-viral therapies
      against hepatitis B.
AB  - BACKGROUND: Results are conflicting with respect to the renal effects of anti
      viral agents used for hepatitis B virus infection. AIM: To compare short and long
      term renal effects in real-life settings and to determine risk factors for renal
      impairment during treatment. METHODS: 2221 treatment-naive patients were
      enrolled. Among these, 895 (302 lamivudine, 27 telbivudine, 282 entecavir, 273
      tenofovir and 11 adefovir initiated patients) had 'repeated measures' of
      creatinine (baseline, 1st, 6th, 12th and 24th month of treatment). Telbivudine
      and adefovir groups were excluded from further analysis because of the low number
      of patients. We calculated the glomerular filtration rate (GFR) using the
      Modification of Diet in Renal Disease (MDRD) formula at each time point.
      Hypophosphataemia was also recorded. Risk factors for renal impairment were
      analysed. RESULTS: Tenofovir caused a decline in GFR at each time point when
      compared to baseline levels. However, lamivudine and entecavir did not change
      GFR. GFR-shifting from >=90 to 60-89 mL/min/1.73 m(2) was comparable among
      groups. The proportion of patients whose baseline creatinine increased more than
      25% was comparable among all anti-virals. GFR showed a decline in patients who
      switched from entecavir to tenofovir. One patient with compensated cirrhosis
      needed to change from tenofovir because of renal safety. Seven and three patients
      developed transient hypophosphataemia in the tenofovir and lamivudine groups,
      respectively. CONCLUSIONS: Although tenofovir caused a decline in GFR,
      differences between the anti-viral agents do not appear to be so impressive. In
      patients with and without renal risk factors at baseline, there is no impact of
      anti-virals, including tenofovir.

PMID- 25982038
TI  - Label-Free Fluorescent Copper Nanoclusters for Genotyping of Deletion and
      Duplication of Duchenne Muscular Dystrophy.
AB  - Real applications in clinical diagnosis of label-free fluorescent copper
      nanoclusters (CuNCs) are demonstrated. Double-strand DNA (dsDNA) can act as an
      effective template for the formation of CuNCs, which can be used to distinguish
      the deletion or duplication genotypes of Duchenne muscular dystrophy (DMD) due to
      different fluorescent intensities. After PCR, the DMD amplicons reacted with
      copper ion by reduction of ascorbic acid and generated fluorescence. The exons of
      the DMD gene were taken as the model analytes for genetic diagnosis. In this
      sensing system, the deletion type does not show fluorescence; on the other hand,
      the duplication type emits higher fluorescence than normal type. Parameters of
      this sensing system were optimized, including PCR conditions, levels of copper
      ion and ascorbate, and reaction time. The DMD-dominated exons 45, 46, and 47 were
      detected, and the method was applied to six samples of DMD patients. The results
      were consistent with those of the multiplex ligation-dependent probe
      amplification method. This strategy was feasible to detect all exons of this
      disease. 

PMID- 25982039
TI  - Universal health coverage: progressive taxes are key.

PMID- 25982040
TI  - Platelet interaction with erythrocytes and propensity to aggregation in essential
      thrombocythaemia.

PMID- 25982041
TI  - Financing universal health coverage--effects of alternative tax structures on
      public health systems: cross-national modelling in 89 low-income and middle
      income countries.
AB  - BACKGROUND: How to finance progress towards universal health coverage in low
      income and middle-income countries is a subject of intense debate. We
      investigated how alternative tax systems affect the breadth, depth, and height of
      health system coverage. METHODS: We used cross-national longitudinal fixed
      effects models to assess the relationships between total and different types of
      tax revenue, health system coverage, and associated child and maternal health
      outcomes in 89 low-income and middle-income countries from 1995-2011. FINDINGS:
      Tax revenue was a major statistical determinant of progress towards universal
      health coverage. Each US$100 per capita per year of additional tax revenues
      corresponded to a yearly increase in government health spending of $9.86 (95% CI
      3.92-15.8), adjusted for GDP per capita. This association was strong for taxes on
      capital gains, profits, and income ($16.7, 9.16 to 24.3), but not for consumption
      taxes on goods and services (-$4.37, -12.9 to 4.11). In countries with low tax
      revenues (<$1000 per capita per year), an additional $100 tax revenue per year
      substantially increased the proportion of births with a skilled attendant present
      by 6.74 percentage points (95% CI 0.87-12.6) and the extent of financial coverage
      by 11.4 percentage points (5.51-17.2). Consumption taxes, a more regressive form
      of taxation that might reduce the ability of the poor to afford essential goods,
      were associated with increased rates of post-neonatal mortality, infant
      mortality, and under-5 mortality rates. We did not detect these adverse
      associations with taxes on capital gains, profits, and income, which tend to be
      more progressive. INTERPRETATION: Increasing domestic tax revenues is integral to
      achieving universal health coverage, particularly in countries with low tax
      bases. Pro-poor taxes on profits and capital gains seem to support expanding
      health coverage without the adverse associations with health outcomes observed
      for higher consumption taxes. Progressive tax policies within a pro-poor
      framework might accelerate progress toward achieving major international health
      goals. FUNDING: Commission of the European Communities (FP7-DEMETRIQ), the
      European Union's HRES grants, and the Wellcome Trust.

PMID- 25982042
TI  - Saving lives with high-flow nasal oxygen.

PMID- 25982043
TI  - Change is good! The Journal of Surgical Research: 2014-2015.

PMID- 25982044
TI  - Hypoparathyroidism after total thyroidectomy: incidence and resolution.
AB  - BACKGROUND: Parathyroid hormone (PTH) levels are often measured after thyroid
      surgery and are used to detect patients at risk for postoperative
      hypoparathyroidism. However, there is a lack of consensus in the literature about
      how to define the recovery of parathyroid gland function and when to classify
      hypoparathyroidism as permanent. The goals of this study were to determine the
      incidence of low postoperative PTH in total thyroidectomy patients and to monitor
      their time course to recovery of parathyroid gland function. METHODS: We
      identified 1054 consecutive patients who underwent a total or completion
      thyroidectomy from January, 2006-December, 2013. Low PTH was defined as a PTH
      measurement <10 pg/mL immediately after surgery. Patients were considered to be
      permanently hypoparathyroid if they had not recovered within 1 y. Recovery of
      parathyroid gland function was defined as PTH >=10 pg/mL and no need for
      therapeutic calcium or activated vitamin D (calcitriol) supplementation to
      prevent hypocalcemic symptoms. RESULTS: Of 1054 total thyroidectomy patients, 189
      (18%) had a postoperative PTH <10 pg/mL. Of those 189 patients, 132 (70%) showed
      resolution within 2 mo of surgery. Notably, 9 (5%) resolved between 6 and 12 mo.
      At 1 y, 20 (1.9%) were considered to have permanent hypoparathyroidism.
      Surprisingly, 50% of those patients had recovery of PTH levels yet still required
      supplementation to avoid symptoms. CONCLUSIONS: Most patients with a low
      postoperative PTH recover function quickly, but it can take up to 1 y for full
      resolution. Hypoparathyroidism needs to be defined not only by PTH levels but
      also by medication requirements.

PMID- 25982046
TI  - Timing of computed tomography scans to identify pediatric postappendectomy
      abscesses.

PMID- 25982045
TI  - Kidney Disease Improving Global Outcomes guidelines and parathyroidectomy for
      renal hyperparathyroidism.
AB  - BACKGROUND: Patients with end-stage renal disease develop hypocalcemia, resulting
      in secondary hyperparathyroidism (SHPT). No clear criterions exist to aid in
      surgical decision making for SHPT. The 2009 Kidney Disease Improving Global
      Outcomes (KDIGO) guidelines provide target ranges for serum calcium, phosphate,
      and parathyroid hormone (PTH) levels in patients with end-stage renal disease.
      Parathyroidectomy can help achieve these targets. The study purpose was to
      examine how parathyroidectomy for SHPT impacts KDIGO targets during immediate and
      long-term follow-up and to evaluate KDIGO categorization with receipt of
      additional surgical intervention. METHODS: A retrospective review of a
      prospective parathyroidectomy database was performed. Included patients had SHPT,
      were on dialysis, and underwent parathyroidectomy. Calcium, phosphate, and PTH
      values were classified as below, within, or above KDIGO targets. RESULTS: Between
      2000 and 2013, 36 patients with SHPT met criteria. Subtotal parathyroidectomy was
      performed in 89%, total parathyroidectomy in 11%. Follow-up time was 54 +/- 7 mo.
      Eight patients (22%) required additional surgery. Twenty-eight patients (76%)
      were alive at the last follow-up. At the last-follow up, patients had phosphate
      (46%), and PTH (17%) above KDIGO ranges. Factors associated with reoperation were
      assessed. Patient PTH within or above target immediately postoperative had a
      higher rate of reoperation (P < 0.01). At the last follow-up, higher phosphate (P
      = 0.054) and PTH (P < 0.001) were associated with higher reoperation rates, but
      calcium (P = 0.33) was not. CONCLUSIONS: PTH and phosphate levels above KDIGO
      indices were associated with additional surgical intervention. Many patients had
      laboratory indices above range at the last follow up, suggesting more patients
      had persistent or recurrent disease than those who underwent reoperation.
      Patients may benefit from more aggressive medical and/or surgical management.

PMID- 25982047
TI  - Hepatic microvascular changes in rat abdominal compartment syndrome.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) is associated with an increased
      rate of multiple organ dysfunction and is an independent marker for mortality.
      Our objective was to develop an animal model to study the mechanisms of tissue
      and microvascular injury associated with ACS at the microscopic level. MATERIALS
      AND METHODS: ACS was established in rats with CO2 insufflation at 20 mm Hg for 2
      h, with an abdominal cast. Sinusoidal perfusion, inflammatory response, and cell
      death were quantified in exteriorized livers. Respiratory and renal dysfunction
      were assessed biochemically and morphologically. Myeloperoxidase levels, a marker
      of neutrophil activation, were measured in the liver, lung, and small intestine.
      RESULTS: Continuously perfused sinusoids were significantly lower in the ACS
      group (81.4 +/- 2.2% versus 99.6% +/- 0.50), with an increase in nonperfused and
      intermittently perfused sinusoids (P < 0.05). Hepatocellular death and the number
      of activated leukocytes in postsinusoidal venules showed 7- and 18-fold
      increases, respectively, in the ACS group (P < 0.05). A significant increase in
      blood urea nitrogen levels in experimental rats was also observed.
      Myeloperoxidase levels were found to be 8-fold higher in lungs of ACS rats
      relative to control (P < 0.05), as well as statistically significant increase in
      the pCO2 and decrease in pH of ACS rats. CONCLUSIONS: We have successfully
      developed a model of ACS with documented evidence of renal and respiratory
      dysfunction. In addition, we have microscopy-confirmed evidence of early
      inflammatory changes and perfusion deficits in the liver with a concomitant
      increase in cell death in the ACS group.

PMID- 25982048
TI  - Pasta Fortified with Potato Juice: Structure, Quality, and Consumer Acceptance.
AB  - The potential of potato juice in relieving gastrointestinal disorders has already
      been proven. Work continues on implementation of this active component into
      products that are widely consumed. In this article, results of an attempt to
      fortify pasta with potato juice are presented and discussed. Fortification is
      performed using fresh and dried juice. The influence of the addition on culinary
      properties of the final product, such as cooking weight and cooking loss, as well
      as microstructure, color, texture, and consumer acceptance were evaluated. It was
      found that potato juice can be used for fortification of pasta both in its fresh
      and dried forms, however the effects on different responses depend on the potato
      juice form used. The addition of potato juice influenced the color of the product
      reducing its lightness and shifting color balances from green to red, yellow
      color saturation was decreased as well. Changes in color were more significant in
      the case of fresh juice addition. The firmness and microstructure of pasta was
      also influenced. The surface microstructure of pasta containing fresh potato
      juice was different from that of the other 2 products being a likely explanation
      of the lower cooking loss observed in its case. In contrast, the consistency of
      dough was strengthened by addition of dried potato juice. Principal components
      analysis indicated that the color change had the most pronounced effect on
      consumer acceptance. Other physicochemical changes were slightly less
      significant. Nevertheless, sensory evaluation proved that functional pasta
      produced with fresh potato juice finds consumer acceptance comparable with that
      of classic pasta. 

PMID- 25982049
TI  - Autonomic control of post-air-breathing tachycardia in Clarias gariepinus
      (Teleostei: Clariidae).
AB  - The African catfish (Clarias gariepinus) is a teleost with bimodal respiration
      that utilizes a paired suprabranchial chamber located in the gill cavity as an
      air-breathing organ. Like all air-breathing fishes studied to date, the African
      catfish exhibits pronounced changes in heart rate (f H) that are associated with
      air-breathing events. We acquired f H, gill-breathing frequency (f G) and air
      breathing frequency (f AB) in situations that require or do not require air
      breathing (during normoxia and hypoxia), and we assessed the autonomic control of
      post-air-breathing tachycardia using an infusion of the beta-adrenergic
      antagonist propranolol and the muscarinic cholinergic antagonist atropine. During
      normoxia, C. gariepinus presented low f AB (1.85 +/- 0.73 AB h(-1)) and a
      constant f G (43.16 +/- 1.74 breaths min(-1)). During non-critical hypoxia (PO2 =
      60 mmHg), f AB in the African catfish increased to 5.42 +/- 1.19 AB h(-1) and f G
      decreased to 39.12 +/- 1.58 breaths min(-1). During critical hypoxia (PO2 = 20
      mmHg), f AB increased to 7.4 +/- 1.39 AB h(-1) and f G decreased to 34.97 +/-
      1.78 breaths min(-1). These results were expected for a facultative air breather.
      Each air breath (AB) was followed by a brief but significant tachycardia, which
      in the critical hypoxia trials, reached a maximum of 143 % of the pre-AB f H
      values of untreated animals. Pharmacological blockade allowed the calculation of
      cardiac autonomic tones, which showed that post-AB tachycardia is predominantly
      regulated by the parasympathetic subdivision of the autonomic nervous system.

PMID- 25982050
TI  - Interaction of physical function, quality of life and depression in Amyotrophic
      lateral sclerosis: characterization of a large patient cohort.
AB  - BACKGROUND: Due to lack of any curative therapy for ALS, symptomatic treatment
      and maintenance of quality of life (QoL) is very important. We aimed to
      characterize the affected domains of QoL in ALS patients and to identify factors
      which are associated with reduced QoL and increased depression. METHODS: 159 ALS
      patients answered standardized questionnaires (Beck Depression Inventory-II, SF
      36 Health Survey questionnaire, revised ALS functional rating scale). Multiple
      regression analysis was used to identify correlations between clinical features
      of ALS patients and depression/QoL scores. In addition, QoL data from ALS
      patients were compared to age-matched reference values representing the German
      normal population. RESULTS: QoL of ALS patients was reduced in nearly all SF-36
      categories. Progression of physical impairment was positively correlated with
      depression but reduced QoL scores only in items directly related to physical
      function. However, QoL was considerably influenced by depression, independently
      from physical impairment. Regarding distinct patient characteristics one of the
      most interesting findings was that increasing age was correlated with
      significantly worse QoL results regarding social functioning. CONCLUSIONS:
      Depressive symptoms had a strong influence on QoL, hence their detection and
      treatment is of particular importance. Different domains of QoL are differently
      affected in subgroups of ALS patients. Being aware of these differences can be
      valuable for both ALS professional and family caregivers and physicians.

PMID- 25982051
TI  - Target-directed screening of the bioactive compounds specifically binding to
      beta2-adrenoceptor in Semen brassicae by high-performance affinity
      chromatography.
AB  - The bioactive ingredients in Semen sinapis were rapidly screened by immobilized
      beta2-adrenoceptor (beta2-AR) and target-directed molecular docking. The methods
      involved the attachment of beta2-AR using any amino group in the receptor, the
      simultaneous separation and identification of the retention compounds by high
      performance affinity chromatography; the binding mechanism of the interesting
      compound to the receptor was investigated by zonal elution and molecular docking.
      Sinapine in Semen sinapis was proved to be the bioactive compound that
      specifically binds to the immobilized receptor. The association constant of
      sinapine to beta2-AR was determined to be 1.36 * 10(5)  M(-1) with a value of
      1.27 * 10(-6)  M for the number of binding sites. Ionic bond was believed to be
      the driving force during the interaction between sinapine and beta2-AR. It is
      possible to become a powerful alternative for rapid screening of bioactive
      compounds from a complex matrix such as traditional Chinese medicine and further
      investigation on the drug-receptor interaction.

PMID- 25982052
TI  - Immediate hypersensitivity caused by cetylpyridinium chloride in a throat spray.

PMID- 25982053
TI  - Cardiac response to early conversion from calcineurin inhibitor to everolimus in
      renal transplant recipients--a three-yr serial echocardiographic substudy of the
      randomized controlled CENTRAL trial.
AB  - BACKGROUND: In transplant recipients, calcineurin inhibitors (CNIs) are
      associated with adverse cardiac effects while mTOR inhibitors have been reported
      to be beneficial. We performed a randomized controlled trial (RCT) in de novo
      renal transplant recipients examining cardiac responses of everolimus vs. CNI.
      METHODS: This was a substudy of the three-yr CENTRAL study, an RCT on safety and
      efficacy of early (week 7 post-engraftment) conversion from cyclosporine A (CsA)
      to everolimus vs. continued CsA. Thirty-nine recipients [median age 64 yr, (range
      31-81)] completed echocardiographic evaluations at baseline, one, and three yr.
      RESULTS: After three yr, there was no difference between groups in left ventricle
      (LV) diastolic function, LV systolic function, LV morphology, and blood pressure
      response. We observed a relevant decrease in LV mass (CsA; 9.6%, p = 0.008, vs.
      everolimus; 7.0% reduction, p = 0.15), stabilized LV diastolic function, and a
      trend toward lower systolic blood pressure with 6 mmHg decrease in both arms
      (CsA, p = 0.08; everolimus, p = 0.14). Diastolic blood pressure was significantly
      reduced (8 mmHg decrease, p = 0.002) only in everolimus patients. CONCLUSIONS:
      After three-yr follow-up, no clinically relevant effect on cardiac function of an
      early conversion from CsA to an everolimus-based immunosuppressive regimen was
      detected in de novo renal transplant recipients.

PMID- 25982055
TI  - Identifying words that emerge into consciousness: Effects of word valence and
      unconscious previewing.
AB  - Words with negative valence capture attention and this increase in attentional
      resources typically enhances perceptual processing. Recently, data using
      continuous flash suppression (CFS) appear to contradict this. In prior research
      when Chinese words were unconsciously presented in CFS and contrast was raised
      until the word was identified, RTs to identify words with negative valence were
      slower than RTs to words with neutral valence. This result might be limited to
      situations where a logographic writing system is used and could reflect a type of
      cognitive aftereffect where previewing the word causes habituation. Data (N=60)
      indicate that results generalize from a logographic (Chinese) to an orthographic
      writing system (English). In addition, when words were previewed in CFS RTs were
      slowed for words with negative valence relative to words with neutral valence and
      this was reversed when words were shown binocularly. Implications for theories of
      unconscious word processing and cognitive aftereffects are discussed. 

PMID- 25982054
TI  - Increasing the Permeability of the Blood-brain Barrier in Three Different Models
      in vivo.
AB  - AIMS: Blood-brain barrier (BBB) plays significant roles in the circumstance
      maintains for the central nervous system (CNS). The dysfunction of the BBB could
      occur in all pathological conditions of CNS diseases, such as ischemic stroke,
      cerebral edema, or inflammatory disorders. However, the comparisons among
      different animal models with a broken BBB in vivo are still need to be further
      studied. METHODS: Here we used three different mice models in vivo, including
      MCAO induce, LPS treatment, and cold injury to mimic the situation in clinic. The
      permeability of BBB in three models was detected by perfusion of Evan's blue dye.
      The functional proteins of the BBB including claudin-5, VE-cadherin, and caveolin
      1 were compared in three different models in vivo. RESULTS: With the
      hyperpermeability of Evan's blue in the three models, both claudin-5 and VE
      cadherin were decreased, while the expression of caveolin-1 was increased. Our
      study showed that BBB dysfunction induced by MCAO in mice was relatively stable,
      reliable, and moderate compared with LPS or cold injury-induced BBB permeability
      models, although the procedural time was generally long and operation complexity
      was hard. Moreover, our study also found that the model of the increased BBB
      permeability by cold injury was severe in the regional cerebral tissue and the
      model treated with LPS was mild in the global cerebral tissue. The operation of
      the two models in vivo was easy, quick, and stable. CONCLUSION: The MCAO model
      was the most suitable for studying the permeability of BBB among the three models
      in vivo.

PMID- 25982056
TI  - Reset a task set after five minutes of mindfulness practice.
AB  - This study aimed to evaluate the impact of a brief mindfulness practice on
      reducing the carryover effect caused by a previous task set and to determine the
      mechanism for its effectiveness. Experiment 1 showed that a memorized color
      interfered with subsequent visual search as a singleton distractor only when
      color was a defining feature for the search target. In Experiment 2, three
      interventions (scene-viewing, distraction, and mindfulness practice) were
      implemented across three groups for five minutes between two blocks; color was
      relevant to search in the first block and irrelevant in the second. Only the
      mindfulness group showed a non-significant carryover effect. Experiment 3
      demonstrated that the scene-viewing participants continued adopting a suppressive
      mode of attentional control on a previously distracting color during letter
      judgment. In contrast, mindfulness practice could reset a task set. Mindfulness
      practice could enhance concentration in the present moment via reconfiguring the
      mode of attentional control. 

PMID- 25982057
TI  - Meditation-induced cognitive-control states regulate response-conflict
      adaptation: Evidence from trial-to-trial adjustments in the Simon task.
AB  - Here we consider the possibility that meditation has an immediate impact on
      information processing. Moreover, we were interested to see whether this impact
      affects attentional input control, as previous observations suggest, or the
      handling of response conflict. Healthy adults underwent a brief single session of
      either focused attention meditation (FAM), which is assumed to increase top-down
      control, or open monitoring meditation (OMM), which is assumed to weaken top-down
      control, before performing a Simon task-which assesses conflict-resolution
      efficiency. While the size of the Simon effect (reflecting the efficiency of
      handling response conflict) was unaffected by type of meditation, the amount of
      dynamic behavioral adjustments (i.e., trial-to-trial variability of the Simon
      effect: the Gratton effect) was considerably smaller after OMM than after FAM.
      Our findings suggest that engaging in meditation instantly creates a cognitive
      control state that has a specific impact on conflict-driven control adaptations. 

PMID- 25982058
TI  - Involvement of soluble scavenger receptor A in suppression of T cell activation
      in patients with chronic hepatitis B.
AB  - BACKGROUND: Scavenger receptor A (SRA) is expressed predominantly in phagocytic
      cells playing an essential role in the host immune defense against invading
      microorganisms. Our previous study reported the presence of SRA in a soluble form
      in patients with infection of hepatitis B viruses (HBV). However, the association
      of soluble SRA with stages of HBV infection and the immune response induced by
      HBV is not fully determined. METHODS: In this study, we detected soluble SRA in
      serum from 29 chronic hepatitis B (CHB) patients, 28 chronic HBV carriers in the
      immune tolerant (IT) stage, 33 in the HBeAg-negative inactive carrier (IC) stage,
      and 22 healthy controls (HCs), respectively. We further analyzed the correlation
      of detected soluble SRA to inflammation and serum viral load. In addition, we
      investigated the regulatory role of soluble SRA in T cell activation, especially
      in CD8(+) T cell response to HBV peptide. RESULTS: We demonstrated that Median
      levels of serum soluble SRA in CHB and IT patients were significantly higher than
      those of IC patients and HCs. Additionally, the concentrations of soluble SRA
      were negatively correlated with alanine transaminase levels in CHB patients. We
      also found that serum concentration of SRA was decreased during telbivudine
      treatment. Expressed SRA extracellular domain suppressed HBV core peptide
      stimulated interferon-gamma and tumor necrosis factor-alpha production in CD8(+)
      T cells, and it bound to T cells in a higher frequency in CHB patients than in
      HCs. Furthermore, we observed that naive human T cells stimulated by anti-CD3 and
      CD28 antibodies in the presence of the recombinant SRA protein had reduced
      activation and proliferation. CONCLUSION: In summary, we determined the level of
      soluble SRA in different stages of CHB patients. SRA might inhibit T cell
      proliferation and activation as a soluble form. These results not only revealed a
      previously unknown feature of soluble SRA in CHB patients but also provided broad
      understanding of SRA in T cell activation.

PMID- 25982063
TI  - Intrathecal enzyme replacement therapy improves motor function and survival in a
      preclinical mouse model of infantile neuronal ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a group of related hereditary
      lysosomal storage disorders characterized by progressive loss of neurons in the
      central nervous system resulting in dementia, loss of motor skills, seizures and
      blindness. A characteristic intralysosomal accumulation of autofluorescent
      storage material occurs in the brain and other tissues. Three major forms and
      nearly a dozen minor forms of NCL are recognized. Infantile-onset NCL (CLN1
      disease) is caused by severe deficiency in a soluble lysosomal enzyme, palmitoyl
      protein thioesterase-1 (PPT1) and no therapy beyond supportive care is available.
      Homozygous Ppt1 knockout mice reproduce the known features of the disease,
      developing signs of motor dysfunction at 5 months of age and death around 8
      months. Direct delivery of lysosomal enzymes to the cerebrospinal fluid is an
      approach that has gained traction in small and large animal models of several
      other neuropathic lysosomal storage diseases, and has advanced to clinical
      trials. In the current study, Ppt1 knockout mice were treated with purified
      recombinant human PPT1 enzyme delivered to the lumbar intrathecal space on each
      of three consecutive days at 6 weeks of age. Untreated PPT1 knockout mice and
      wild-type mice served as additional controls. Four enzyme concentration levels
      (0, 2.6, 5.3 and 10.6 mg/ml of specific activity 20 U/mg) were administered in a
      volume of 80 MUl infused over 8 min. Each group consisted of 16-20 mice. The
      treatment was well tolerated. Disease-specific survival was 233, 267, 272, and
      284days for each of the four treatment groups, respectively, and the effect of
      treatment was highly significant (p<0.0001). The timing of motor deterioration
      was also delayed. Neuropathology was improved as evidenced by decreased
      autofluorescent storage material in the spinal cord and a decrease in CD68
      staining in the cortex and spinal cord. The improvements in motor function and
      survival are similar to results reported for preclinical studies involving other
      lysosomal storage disorders, such as CLN2/TPP1 deficiency, for which
      intraventricular ERT is being offered in clinical trials. If ERT delivery to the
      CSF proves to be efficacious in these disorders, PPT1 deficiency may also be
      amenable to this approach.

PMID- 25982064
TI  - Molecular phenotype of tissue-nonspecific alkaline phosphatase with a proline
      (108) to leucine substitution associated with dominant odontohypophosphatasia.
AB  - Hypophosphatasia (HPP) is a genetic disease characterized by defective
      calcification of hard tissues such as bone and teeth accompanying deficiency of
      serum alkaline phosphatase (ALP) activity. Its development results from various
      mutations in the ALPL gene encoding tissue-nonspecific ALP (TNSALP). HPP is known
      to be transmitted in an autosomal recessive or autosomal dominant manner. A point
      mutation (c.323C>T) in the ALPL gene leading to a proline to leucine substitution
      at position 108 of TNSALP was first reported in a patient diagnosed with odonto
      HPP (M Herasse et al., J Med Genet 2003;40:605-609), although the effects of this
      mutation on the TNSALP molecule have not been elucidated. To understand the
      molecular basis of this dominantly transmitted HPP, we first characterized TNSALP
      (P108L) by expressing it in COS-1 cells transiently. In contrast to wild-type
      TNSALP (WT), TNSALP (P108L) showed virtually no ALP activity. When coexpressed
      with TNSALP (WT), TNSALP (P108L) significantly inhibited the enzyme activity of
      TNSALP (WT), confirming that this mutant TNSALP exerts a dominant negative effect
      on TNSALP (WT). Using immunofluorescence and digestion with phosphatidylinositol
      specific phospholipase C, we demonstrated that TNSALP (P108L) was anchored to the
      cell surface via glycosylphosphatidylinositol-like TNSALP (WT) in a Tet-On CHO
      cell expression system. Consistent with this, TNSALP (P108L) acquired endo-beta-N
      acetylglucosaminidase H resistance and sialic acids, as evidenced by glycosidase
      treatments. Importantly, TNSALP (WT) largely formed a functional dimeric
      structure, while TNSALP (P108L) was found to be present as a monomer in the cell.
      This indicates that the molecular structure of TNSALP is affected by a missense
      mutation at position 108, which is in contact with the active site, such that it
      no longer assembles into the functional dimeric form. Collectively, these results
      may explain why TNSALP (P108L) loses its ALP activity, even though it is able to
      gain access to the cell surface. 

PMID- 25982065
TI  - Various lamin A/C mutations alter expression profile of mesenchymal stem cells in
      mutation specific manner.
AB  - Various mutations in LMNA gene, encoding for nuclear lamin A/C protein, lead to
      laminopathies and contribute to over ten human disorders, mostly affecting
      tissues of mesenchymal origin such as fat tissue, muscle tissue, and bones.
      Recently it was demonstrated that lamins not only play a structural role
      providing communication between extra-nuclear structures and components of cell
      nucleus but also control cell fate and differentiation. In our study we assessed
      the effect of various LMNA mutations on the expression profile of mesenchymal
      multipotent stem cells (MMSC) during adipogenic and osteogenic differentiation.
      We used lentiviral approach to modify human MMSC with LMNA-constructs bearing
      mutations associated with different laminopathies--G465D, R482L, G232E, R527C,
      and R471C. The impact of various mutations on MMSC differentiation properties and
      expression profile was assessed by colony-forming unit analysis, histological
      staining, expression of the key differentiation markers promoting adipogenesis
      and osteogenesis followed by the analysis of the whole set of genes involved in
      lineage-specific differentiation using PCR expression arrays. We demonstrate that
      various LMNA mutations influence the differentiation efficacy of MMSC in mutation
      specific manner. Each LMNA mutation promotes a unique expression pattern of genes
      involved in a lineage-specific differentiation and this pattern is shared by the
      phenotype-specific mutations.

PMID- 25982067
TI  - Multiclassifier system with hybrid learning applied to the control of
      bioprosthetic hand.
AB  - In this paper the problem of recognition of the intended hand movements for the
      control of bio-prosthetic hand is addressed. The proposed method is based on
      recognition of electromiographic (EMG) and mechanomiographic (MMG) biosignals
      using a multiclassifier system (MCS) working in a two-level structure with a
      dynamic ensemble selection (DES) scheme and original concepts of competence
      function. Additionally, feedback information coming from bioprosthesis sensors on
      the correct/incorrect classification is applied to the adjustment of the
      combining mechanism during MCS operation through adaptive tuning competences of
      base classifiers depending on their decisions. Three MCS systems operating in
      decision tree structure and with different tuning algorithms are developed. In
      the MCS1 system, competence is uniformly allocated to each class belonging to the
      group indicated by the feedback signal. In the MCS2 system, the modification of
      competence depends on the node of decision tree at which a correct/incorrect
      classification is made. In the MCS3 system, the randomized model of classifier
      and the concept of cross-competence are used in the tuning procedure.
      Experimental investigations on the real data and computer-simulated procedure of
      generating feedback signals are performed. In these investigations classification
      accuracy of the MCS systems developed is compared and furthermore, the MCS
      systems are evaluated with respect to the effectiveness of the procedure of
      tuning competence. The results obtained indicate that modification of competence
      of base classifiers during the working phase essentially improves performance of
      the MCS system and that this improvement depends on the MCS system and tuning
      method used. 

PMID- 25982069
TI  - Examining the levels of BDNF and cortisol in children and adolescent victims of
      sexual abuse--a preliminary study.
AB  - BACKGROUND: Previous reports have suggested the biological and psychological
      effects of trauma induced by cortisol and brain-derived neurotrophic factor
      (BDNF). The present study compared the levels of BDNF, cortisol, and
      adrenocorticotropic hormone (ACTH) in children and adolescent victims of sexual
      abuse to those without a trauma history. METHODS: The study was conducted in the
      Department of Child Psychiatry at Dicle University. The study included 44
      children (M/F: 12/32) aged between 8 and 17years who experienced sexual abuse
      with 42 age-and gender-matched children who did not have a history of trauma.
      Cortisol, ACTH, and BDNF levels were measured using ELISA. RESULTS: Cortisol
      levels were higher and BDNF levels were significantly lower in the victims of
      sexual abuse compared to the control group. The mean time that elapsed from the
      initial sexual abuse occurrence until the date of examination was 22.7+/
      21.7months. The evaluation of the relationship between this time span and
      cortisol levels revealed that cortisol levels decreased with increasing time
      after trauma. Cortisol and BDNF levels were lower in the victims who experienced
      multiple sexual assaults. CONCLUSIONS: The results of the present study suggest
      that cortisol and BDNF could be biological molecular mediators of the effects of
      trauma on biological and psychological systems. This is the first report on the
      effects of cortisol and BDNF induced trauma in child and adolescent victims of
      sexual abuse.

PMID- 25982068
TI  - Expression of myostatin in early postnatal mouse masseter and rectus femoris
      muscles.
AB  - AIMS: Myostatin (Mstn) is a member of the transforming growth factor-beta (TGF
      beta) family that inhibits muscle differentiation. In this study, we aimed to
      identify the relationships between Mstn, thyroid hormone receptor alpha
      (TRalpha), and myosin heavy chain (MyHC) isoform expression during early
      postnatal development. METHODS: We investigated the expression of Mstn, TRalpha,
      and MyHCs (embryonic, slow, IIa, IIb, and IIx) using quantitative real-time RT
      PCR and ELISA (Mstn) in postnatal mouse muscles between day 0 and day 10. We also
      examined the correlations between Mstn, TR and MyHCs during the early development
      of mouse masseter muscle (MM) and rectus femoris muscle (RFM). RESULTS: Distinct
      Mstn mRNA expression patterns were observed in the two muscles despite nearly non
      significant changes in the Mstn protein abundance in MM. The expression pattern
      of the TRalpha mRNA in the MM differed from that observed in the RFM. The
      expression of MyHC IIa, IIb and IIx mRNAs increased in the MM and decreased in
      the RFM from day 0 to day 10, whereas embryonic fiber MyHC mRNA expression was
      similar in both muscle types. Principal component analysis showed the existence
      of a correlation between: (1) TRalpha and MyHC, (2) Mstn and MyHC, and (3)
      TRalpha and Mstn in MM. The correlations were different in RFM and MM. Cluster
      analyses identified the distinct clusters: cluster 1, days 0-4 for the MM and day
      0 for the RFM; cluster 2, day 6 for the MM and day 2 for the RFM; and cluster 3,
      days 8-10 for the MM and days 4-10 for the RFM. CONCLUSIONS: These data suggest
      that TRalpha influences MyHC expression in both muscle types. In addition, Mstn
      has a limited effect in the MM related to the expression of individual MyHCs, as
      opposed to its role in the RFM, at early postnatal developmental stages. TRalpha
      could be involved in regulating both the temporal expression of MyHCs and Mstn at
      the early postnatal stages in the MM and RFM.

PMID- 25982066
TI  - Rapid 3-D delineation of cell nuclei for high-content screening platforms.
AB  - High-resolution three-dimensional (3-D) microscopy combined with multiplexing of
      fluorescent labels allows high-content analysis of large numbers of cell nuclei.
      The full automation of 3-D screening platforms necessitates image processing
      algorithms that can accurately and robustly delineate nuclei in images with
      little to no human intervention. Imaging-based high-content screening was
      originally developed as a powerful tool for drug discovery. However, cell
      confluency, complexity of nuclear staining as well as poor contrast between
      nuclei and background result in slow and unreliable 3-D image processing and
      therefore negatively affect the performance of studying a drug response. Here, we
      propose a new method, 3D-RSD, to delineate nuclei by means of 3-D radial
      symmetries and test it on high-resolution image data of human cancer cells
      treated by drugs. The nuclei detection performance was evaluated by means of
      manually generated ground truth from 2351 nuclei (27 confocal stacks). When
      compared to three other nuclei segmentation methods, 3D-RSD possessed a better
      true positive rate of 83.3% and F-score of 0.895+/-0.045 (p-value=0.047).
      Altogether, 3D-RSD is a method with a very good overall segmentation performance.
      Furthermore, implementation of radial symmetries offers good processing speed,
      and makes 3D-RSD less sensitive to staining patterns. In particular, the 3D-RSD
      method performs well in cell lines, which are often used in imaging-based HCS
      platforms and are afflicted by nuclear crowding and overlaps that hinder feature
      extraction. 

PMID- 25982070
TI  - Clinicians with dyslexia: a systematic review of effects and strategies.
AB  - BACKGROUND: For educators, an awareness of the impact of dyslexia on learners in
      the clinical workplace is vital: first, to be able to identify whether dyslexia
      may underlie certain traits and behaviours; and second, to be able to provide
      appropriate advice and support when dyslexia is identified. We reviewed the
      primary research evidence concerning the effects of dyslexia on clinicians (in or
      after training) in the workplace, and adaptive strategies ('workarounds') that
      are presently in use. METHODS: A systematic search of literature was undertaken,
      followed by a narrative review of studies selected as meeting the inclusion
      criteria. The review used a priori research questions and focused on studies
      based on primary research evidence. RESULTS: The review identified five key
      studies on qualified doctors or nurses with dyslexia. The impact of dyslexia on
      doctors can include: writing and calculating prescriptions, writing patient
      notes, and prioritising and making referrals. Strategies to minimise the effects
      of dyslexia include the use of adaptive technologies, the need for more time for
      mentors and supervisors, and an awareness of 'enabling' and 'disabling'
      environments. An awareness of the impact of dyslexia on learners in the clinical
      workplace is vital DISCUSSION: The difficulties associated with dyslexia are
      varied and may be unexpected. Medical educators must therefore be aware of
      dyslexia and its impact. When supporting a trainee with dyslexia, there is
      guidance available but educators may struggle to identify strategies and
      resources that are evidence based, so further research is required.

PMID- 25982071
TI  - A self adaptive hybrid enhanced artificial bee colony algorithm for continuous
      optimization problems.
AB  - The artificial bee colony (ABC) algorithm is one of popular swarm intelligence
      algorithms that inspired by the foraging behavior of honeybee colonies. To
      improve the convergence ability, search speed of finding the best solution and
      control the balance between exploration and exploitation using this approach, we
      propose a self adaptive hybrid enhanced ABC algorithm in this paper. To evaluate
      the performance of standard ABC, best-so-far ABC (BsfABC), incremental ABC
      (IABC), and the proposed ABC algorithms, we implemented numerical optimization
      problems based on the IEEE Congress on Evolutionary Computation (CEC) 2014 test
      suite. Our experimental results show the comparative performance of standard ABC,
      BsfABC, IABC, and the proposed ABC algorithms. According to the results, we
      conclude that the proposed ABC algorithm is competitive to those state-of-the-art
      modified ABC algorithms such as BsfABC and IABC algorithms based on the benchmark
      problems defined by CEC 2014 test suite with dimension sizes of 10, 30, and 50,
      respectively. 

PMID- 25982072
TI  - A plain X-ray in peritoneal dialysis-related peritonitis.

PMID- 25982073
TI  - Does lactate account for all of the increase in anion gap in cases of metformin
      induced lactic acidosis?

PMID- 25982074
TI  - Optimization of 2,4-diamino-5-fluoropyrimidine derivatives as protein kinase C
      theta inhibitors with mitigated time-dependent drug-drug interactions and P-gp
      liability.
AB  - Protein kinase C theta (PKCtheta) plays a critical role in T cell signaling and
      has therapeutic potential for T cell-mediated diseases such as transplant
      rejection and rheumatoid arthritis. Here, a series of 2,4-diamino-5
      fluoropyrimidine derivatives were prepared and evaluated for their inhibition of
      PKCtheta. Of these compounds, 14f was found to exhibit potent PKCtheta inhibitory
      activity and significantly weak CYP3A4 time-dependent inhibition (TDI) and P
      glycoprotein (P-gp) liability.

PMID- 25982075
TI  - Discovery of biphenyl-aryl ureas as novel VEGFR-2 inhibitors. Part 4: exploration
      of diverse hinge-binding fragments.
AB  - VEGFR-2 plays an essential role in angiogenesis and is an important target for
      cancer therapy. A series of biphenyl-aryl ureas were synthesized and evaluated as
      novel VEGFR-2 inhibitors. The pyridine, methylamine carbonyl pyridine and
      pivaloyl amide pyridine were introduced as novel hinge binding fragment. The
      majority of title compounds displayed potent VEGFR-2 inhibition. In particular,
      L1, L9, W14 and W15 exhibited significant enzymatic inhibitory activity with IC50
      values of 0.36nM, 0.22nM, 0.15nM and 0.14nM. Compounds L1, L9 and W15 displayed
      potent antiproliferative activity against A549 and SMMC-7721 cells. SAR study
      suggested that incorporation of 3-trifluoromethyl and methylamine carbonyl on
      terminal pyridine could improve VEGFR-2 inhibitory activity. Molecular docking
      illustrated that urea moiety formed two critical hydrogen bonds with the DFG
      residues of VEGFR-2. The results indicated that these biphenyl-aryl ureas could
      serve as promising lead compounds for further optimization.

PMID- 25982076
TI  - Systematic assessment of scaffold hopping versus activity cliff formation across
      bioactive compound classes following a molecular hierarchy.
AB  - Scaffold hopping and activity cliff formation define opposite ends of the
      activity landscape feature spectrum. To rationalize these events at the level of
      scaffolds, active compounds involved in scaffold hopping were required to contain
      topologically distinct scaffolds but have only limited differences in potency,
      whereas compounds involved in activity cliffs were required to share the same
      scaffold but have large differences in potency. A systematic search was carried
      out for compounds involved in scaffold hopping and/or activity cliff formation.
      Results obtained for compound data sets covering more than 300 human targets
      revealed clear trends. If scaffolds represented multiple but fewer than 10 active
      compounds, nearly 90% of all scaffolds were exclusively involved in hopping
      events. With increasing compound coverage, the fraction of scaffolds involved in
      both scaffold hopping and activity cliff formation significantly increased to
      more than 50%. However, ~40% of the scaffolds representing large numbers of
      active compounds continued to be exclusively involved in scaffold hopping. More
      than 200 scaffolds with broad target coverage were identified that consistently
      represented potent compounds and yielded an abundance of scaffold hops in the low
      nanomolar range. These and other subsets of scaffolds we characterized are of
      prime interest for structure-activity relationship (SAR) exploration and compound
      design. Therefore, the complete scaffold classification generated in the course
      of our analysis is made freely available.

PMID- 25982077
TI  - Chemistry and biology of protein and inositol phosphorylation.

PMID- 25982078
TI  - Design, synthesis, and biological evaluation of a series of alkoxy-3
      indolylacetic acids as peroxisome proliferator-activated receptor gamma/delta
      agonists.
AB  - A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome
      proliferator-activated receptor (PPAR) agonists. Structure-activity relationship
      study indicated that PPARalpha/gamma/delta activities were dependent on the
      nature of the hydrophobic group, the attachment position of the alkoxy linker to
      the indole ring, and N-alkylation of indole nitrogen. Some compounds presented
      significant PPARgamma/delta activity and molecular modeling suggested their
      putative binding modes in the ligand binding domain of PPARgamma. Of these,
      compound 51 was selected for in vivo study via an evaluation of microsomal
      stability in mouse and human liver. Compound 51 lowered the levels of fasting
      blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When
      compound 51 was treated, hepatic triglycerides level and the size of adipocytes
      in white adipose tissue of db/db mice were also reduced as opposed to treatment
      with rosiglitazone. Taken together, compound 51 shows high potential warranting
      further studies in models for diabetes and related metabolic disorders and may be
      in use as a chemical tool for the understanding of PPAR biology.

PMID- 25982079
TI  - Differences in physical activity domains, guideline adherence, and weight history
      between metabolically healthy and metabolically abnormal obese adults: a cross
      sectional study.
AB  - BACKGROUND: Despite the accepted health consequences of obesity, emerging
      research suggests that a significant segment of adults with obesity are
      metabolically healthy (MHO). To date, MHO individuals have been shown to have
      higher levels of physical activity (PA), but little is known about the importance
      of PA domains or the influence of weight history compared to their metabolically
      abnormal (MAO) counterpart. OBJECTIVE: To evaluate the relationship between PA
      domains, PA guideline adherence, and weight history on MHO. METHODS: Pooled
      cycles of the National Health and Nutritional Examination Survey (NHANES) 1999
      2006 (>=20 y; BMI >= 30 kg/m(2); N = 2,753) and harmonized criteria for metabolic
      syndrome (MetS) were used. Participants were categorized as "inactive" (no
      reported PA), "somewhat active" (>0 to < 500 metabolic equivalent (MET)
      min/week), and "active" (PA guideline adherence, >= 500 MET min/week) according
      to each domain of PA (total, recreational, transportation and household).
      Logistic and multinomial regressions were modelled for MHO and analyses were
      adjusted for age, sex, education, ethnicity, income, smoking and alcohol intake.
      RESULTS: Compared to MAO, MHO participants were younger, had lower BMI, and were
      more likely to be classified as active according to their total and recreational
      PA level. Based on total PA levels, individuals who were active had a 70% greater
      likelihood of having the MHO phenotype (OR = 1.70, 95% CI: 1.19-2.43); however,
      once stratified by age (20-44 y; 45-59 y; and; >=60 y), the association remained
      significant only amongst those aged 45-59 y. Although moderate and vigorous PA
      were inconsistently related to MHO following adjustment for covariates, losing
      >=30 kg in the last 10 y and not gaining >=10 kg since age 25 y were significant
      predictors of MHO phenotype for all PA domains, even if adherence to the PA
      guidelines were not met. CONCLUSION: Although PA is associated with MHO, the
      beneficial effects of PA may be moderated by longer-term changes in weight.
      Longitudinal analysis of physical activity and weight change trajectories are
      necessary to isolate the contribution of duration of obesity, PA behaviours, and
      longer-term outcomes amongst MHO individuals.

PMID- 25982081
TI  - Emotional Intelligence of Women Who Experience Domestic Violence.
AB  - Violence in family constitutes serious social and psychological problem with
      harmful consequences leading, among others, to changes in emotional functioning
      of victim and, secondarily, also perpetrator. The aim of this study was to
      examine emotional intelligence of women experiencing domestic violence. INTE,
      i.e. Polish version of "Assessing Emotional Scale" by Schutte, was used to study
      two groups of women. Study (criterion) group included 40 women aged 23-47 years
      (mean age 35.28) using assistance of Crisis Intervention Centre due to
      experienced domestic violence. Reference (control) group was well-matched in
      terms of socio-demographic characteristics and consisted of 140 women not
      experiencing domestic violence. Study women experiencing domestic violence have
      significantly lower scores on all INTE indicators (general score, Factor I and
      Factor II). Women not experiencing domestic violence achieved significantly
      higher scores on Factor I than on Factor II. In this group all INTE components
      (general score, Factor I, Factor II) are positively correlated, whereas in group
      of women experiencing domestic violence there is no significant correlation
      between Factor I and Factor II and coefficients are lower. Emotional intelligence
      of study women experiencing domestic violence is lower than emotional
      intelligence of women not experiencing domestic violence. Their abilities and
      skills making up emotional intelligence are also less developed. The internal
      structure of emotional intelligence of study women experiencing domestic violence
      differs from emotional intelligence of women not experiencing domestic violence.
      It seems advisable to consider emotional intelligence in the process of providing
      women experiencing domestic violence with psychosocial help.

PMID- 25982080
TI  - The Association Between Breastfeeding Exposure and Duration, Neuropsychological
      Deficits, and Psychopathic Personality Traits in Offspring: The Moderating Role
      of 5HTTLPR.
AB  - A wealth of research has revealed that a shorter duration of breastfeeding during
      infancy can increase the risk of various maladaptive traits, including
      neuropsychological deficits. Despite the number of studies that have been
      conducted on the topic, few studies have explored whether the effects of
      breastfeeding on neuropsychological functioning and personality features persist
      into adulthood. Furthermore, very little research to date has examined whether
      this relationship is moderated by specific indicators of genetic risk. The
      current study examines the direct and interactive effects of breastfeeding
      experiences and the serotonin transporter polymorphism (5HTTLPR) on
      neuropsychological deficits and psychopathic personality traits. Using data from
      the National Longitudinal study of Adolescent Health, we find that no exposure to
      breastfeeding and a shorter duration of breastfeeding significantly increase the
      risk of exhibiting neuropsychological deficits during adolescence and early
      adulthood as well as psychopathic personality traits during adulthood. The
      results also reveal a number of gene * environment interactions between 5HTTLPR,
      breastfeeding exposure and breastfeeding duration in the prediction of
      neuropsychological deficits, but not in the prediction of psychopathic
      personality traits.

PMID- 25982082
TI  - The Formation of Marijuana Risk Perception in a Population of Substance Abusing
      Patients.
AB  - Risk perception has been shown to be protective with regard to marijuana use.
      Notably, the risk perception of marijuana in individuals with substance abuse
      problems varies significantly from that of the general public. Understanding how
      risk perception is formed in substance users could explain these differences and
      help predict the consequences of policy changes. Using this framework, we
      explored risk perception and its formation in a sample of substance abusing
      veterans. Semi-structured interviews were conducted with veterans who were
      receiving treatment for substance abuse. Interviews were recorded digitally,
      transcribed verbatim, and analyzed using inductive thematic analysis. A prominent
      perspective among the 31 participants was that marijuana is significantly
      different from other drugs because it is safe, not addictive, not associated with
      physical withdrawal, and has less overt behavioral effects than other substances.
      Many of these participants drew upon their own innocuous experiences with the
      drug in developing this perspective, more so than information from any other
      source. A contrasting narrative emphasized marijuana's capacity to cause negative
      social consequences, act as a gateway to the use of other, more harmful
      substances, and cause paranoia or worsen psychosis. In conclusion, individual
      experience with marijuana featured more prominently in informing risk perception
      than any other source of information. Our results and previous literature suggest
      that the significant disconnect between the individual experiences of substance
      users and the current clinical and legal policy towards marijuana may weaken the
      legitimacy of public policy or the authority of the medical community. 

PMID- 25982083
TI  - Psychopathological Predictors of Indirect Self-Destructiveness in Patients with
      Schizophrenia.
AB  - Behaviours causing harm to the individual are generally called self-destructive
      behaviours. For some time now, direct/acute self-destructiveness has been
      distinguished from indirect/chronic self-destructiveness. Indirectly self
      destructive behaviours occur not only in healthy people (examined in most of the
      studies) but also in mentally ill individuals, which has not been researched. The
      aim of this study has been to explore psychopathological (clinical) predictors of
      indirect self-destructiveness in patients with schizophrenia. Research was
      conducted among 200 patients suffering from paranoid schizophrenia (Sc)
      (according to ICD-10); average age: 37.15 (27-58) years. To assess indirect self
      destructiveness, the Polish version of the "Chronic Self-Destructiveness Scale"
      was applied, whereas, to examine psychopathological characteristics, the Polish
      version of the "Minnesota Multiphasic Personality Inventory-2" was used. The
      correlation-regression procedure was followed. There were many statistically
      significant correlations, among which the strongest association occurred between
      indirect self-destructiveness and Sc and paranoia (Pa) scales (0.522 and 0.435
      respectively). Significant predictors were found to be schizophrenia (Sc; R:
      0.545; beta: 0.412), lack of ego mastery, conative (Sc2b; R: 0.633; beta: 0.632),
      and persecutory ideas (Pa1; R: 0.506; beta: 0.335). schizophrenic disorders were
      a predictor explaining the indirect self-destructiveness syndrome in the
      patients. That aspect of psycho(patho)logical functioning, i.e. indirect self
      destructiveness, which is strongly associated with schizophrenic and paranoid
      symptoms/disorders, should be considered in therapeutic work as well.

PMID- 25982084
TI  - Fruit calcium accumulation coupled and uncoupled from its transpiration in
      kiwifruit.
AB  - Accumulation of Ca in several fleshy fruit is often supposed to depend, among
      others, by climatic variables driving fruit transpiration. This study tests the
      whole causal chain hypothesis: VPD -> fruit transpiration -> Ca accumulation.
      Also there are evidences that relationship between fruit transpiration and Ca
      content is not always clear, hence the hypothesis that low VPD reduces the
      fraction of xylemic water destined to transpiration was tested by examining the
      water budget of fruit. Attached fruits of Actinidia deliciosa were subjected to
      Low (L) and High (H) VPD. Their transpiration was measured from early after fruit
      set to day 157 after full bloom (DAFB). Fruits were picked at 70, 130 and 157
      DAFB for Ca and K determinations and for water budget analysis. Cumulative
      transpired water was ~ 70 g and ~ 16 g H2O f(-1) in HVPD and LVPD, respectively.
      Calcium accumulated linearly (R(2) = 0.71) with cumulative transpiration when VPD
      was high, while correlation was weaker (R(2) = 0.24) under LVPD. Under low VPD
      the fraction of xylem stream destined to transpiration declined to 40-50%.
      Results suggest that Ca accumulation is coupled to cumulative transpiration under
      high VPD because under that condition cumulative transpiration equals xylem
      stream (which carry the nutrient). At LVPD, Ca gain by fruit is uncoupled from
      transpiration because ~ 60% of the xylemic water is needed to sustain fruit
      growth. Results will apply to most fruits (apples, tomatoes, capsicum, grapes
      etc.) since most suffer Ca deficiency disorders and grow in changing environments
      with variable VPD, also they could be supportive for the implementation of fruit
      quality models accounting also for mineral compositions and for a
      reinterpretation of certain field practices aimed at naturally improve fruit Ca
      content.

PMID- 25982085
TI  - Testosterone and obesity.
AB  - Testosterone is a key hormone in the pathology of metabolic diseases such as
      obesity. Low testosterone levels are associated with increased fat mass
      (particularly central adiposity) and reduced lean mass in males. These
      morphological features are linked to metabolic dysfunction, and testosterone
      deficiency is associated with energy imbalance, impaired glucose control, reduced
      insulin sensitivity and dyslipidaemia. A bidirectional relationship between
      testosterone and obesity underpins this association indicated by the hypogonadal
      obesity cycle and evidence weight loss can lead to increased testosterone levels.
      Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose
      control and energy utilization are apparent and often tissue specific with
      differential effects noted in different regional fat depots, muscle and liver to
      potentially explain the mechanisms of testosterone action. Testosterone
      replacement therapy demonstrates beneficial effects on measures of obesity that
      are partially explained by both direct metabolic actions on adipose and muscle
      and also potentially by increasing motivation, vigour and energy allowing obese
      individuals to engage in more active lifestyles. The degree of these beneficial
      effects may be dependent on the treatment modality with longer term
      administration often achieving greater improvements. Testosterone replacement may
      therefore potentially be an effective adjunctive treatment for weight management
      in obese men with concomitant hypogonadism. 

PMID- 25982086
TI  - Spinal and supraspinal N-methyl-D-aspartate and melanocortin-1 receptors
      contribute to a qualitative sex difference in morphine-induced hyperalgesia.
AB  - Morphine elicits a paradoxical state of increased pain sensitivity, known as
      morphine-induced hyperalgesia (MIH), which complicates its clinical efficacy. We
      have previously shown that systemic injections of N-methyl-d-aspartate receptor
      (NMDAR) and melanocortin-1 receptor (MC1R) antagonists sex-dependently reverse
      MIH during morphine infusion (40mg/kg/24h) in male and female mice, respectively.
      This qualitative sex difference is ovarian hormone dependent, as NMDAR
      antagonists reverse MIH in ovariectomized females but are rendered ineffective
      following progesterone injection in OVX mice. Here, we utilized intrathecal and
      intracerebroventricular injection paradigms to assess the contribution of spinal
      and supraspinal receptors to this sex difference in male and female CD-1 mice.
      Specifically, we injected NMDAR and MC1R selective antagonists, MK-801 and MSG606
      respectively, during morphine infusion. Results illustrated that both spinal and
      supraspinal MK-801 and MSG606 selectively reversed MIH in males and females,
      respectively, during morphine infusion. Furthermore, while MK-801 reversed MIH in
      ovariectomized (OVX) females, MSG606 was most effective in doing so in this same
      group following an acute subcutaneous progesterone injection. The present studies
      thus indicate that both spinal and supraspinal NMDARs and MC1Rs underlie the
      qualitative sex difference observed during morphine infusion in mice, and that
      the receptors in these loci are also sensitive to sex steroidal modulation. 

PMID- 25982087
TI  - Homer1a-dependent recovery from depression-like behavior by photic stimulation in
      mice.
AB  - A significant number of depressed people are resistant to drug therapy. Promising
      alternative therapy may be brain stimulation achievable by diverse methods. In a
      mouse model of depression, we previously investigated the mechanisms by which
      repetitive transcranial magnetic stimulation (rTMS) reverses depression-like
      behavior, and found an essential involvement of the immediate early gene product
      Homer1a. Home1a is known to be expressed not just by rTMS but also by photic
      stimulation (PS) via activation of the retino-geniculo-cortical pathway,
      suggesting that PS may have an antidepressant effect. This was tested by using a
      two-phase version of forced swimming (FS), in which the first phase consists of a
      10-min swimming for 5 consecutive days and the second phase takes place at a 4
      week interval for testing behavior. During the 4-week period, PS was applied
      everyday (300lx, 2Hz for 6h daily). After the last swimming, the brains were
      removed and subjected to quantitative RT-PCR and electrophysiological analysis.
      The 4-week-long PS alleviated depression-like behavior to the extent comparable
      to that obtained with rTMS previously. Homer1a expression was drastically reduced
      by FS and recovered by PS. Consistently with our previous studies, activity of
      the large conductance calcium-activated potassium (BK) channel was facilitated by
      PS in a Homer1a-dependent manner. PS may thus have a potential utility for
      depression therapy. Furthermore, given that Homer1a is implicated in various
      neuropsychiatric disorders, brain stimulations that induce Homer1a expression,
      such as rTMS or PS, may have a wider applicability than currently thought. 

PMID- 25982088
TI  - Ready to give up on life: The lived experience of elderly people who feel life is
      completed and no longer worth living.
AB  - In the Netherlands, there has been much debate on the question whether elderly
      people over 70 who are tired of life and who consider their life to be completed,
      should have legal options to ask for assisted dying. So far there has been little
      research into the experiences of these elderly people. In order to develop
      deliberate policy and care that targets this group of elderly people, it is
      necessary to understand their lifeworld. The aim of this paper is to describe the
      phenomenon 'life is completed and no longer worth living' from a lifeworld
      perspective, as it is lived and experienced by elderly people. Between April to
      December 2013, we conducted 25 in-depth interviews. A reflective lifeworld
      research design, drawing on the phenomenological tradition, was used during the
      data gathering and data analysis. The essential meaning of the phenomenon is
      understood as 'a tangle of inability and unwillingness to connect to one's actual
      life', characterized by a permanently lived tension: daily experiences seem
      incompatible with people's expectations of life and their idea of whom they are.
      While feeling more and more disconnected to life, a yearning desire to end life
      is strengthened. The experience is further explicated in its five constituents:
      1) a sense of aching loneliness; 2) the pain of not mattering; 3) the inability
      to express oneself; 4) multidimensional tiredness; and 5) a sense of aversion
      towards feared dependence. This article provides evocative and empathic lifeworld
      descriptions contributing to a deeper understanding of these elderly people and
      raises questions about a close association between death wishes and depression in
      this sample. 

PMID- 25982089
TI  - Conservative treatment of traumatic shoulder instability: a case series study.
AB  - PURPOSE: The aim of this case series study was to evaluate the efficacy of a
      rehabilitative approach to restoring stability, range of motion, and function of
      shoulder joint in non-operated adults presenting a first episode of traumatic
      anterior shoulder dislocation. METHODS: In this case series study, we evaluated
      patients aged from 20 to 44 years, with diagnosis of first episode of traumatic
      anterior shoulder dislocation. All participants underwent a conservative
      treatment protocol, lasting 3 months. The primary outcome measure was the Rowe
      score for instability. Follow-up evaluations were done at 3, 6, 12, and 24
      months. RESULTS: We evaluated 32 participants mean aged 27.94 +/- 2.23 years. At
      the baseline (T 0), the participants had a mean Rowe score of instability of
      44.53 +/- 7.00 SD, where 81.25% had a poor score and 18.75% had a fair score. At
      24 months (T 4), the Rowe score for instability was 79.84 +/- 6.66 SD. 21.88% of
      patients had a fair score, 71.87% had a good score, and 6.25% had an excellent
      score. CONCLUSIONS: We showed that our rehabilitative approach seems to be
      effective in the conservative management of shoulder instability in adults with
      first episode of traumatic anterior shoulder dislocation, not involved in sport
      activity, and not overhead workers.

PMID- 25982090
TI  - Prognostic factors of extracorporeal shock wave therapy for tendinopathies.
AB  - INTRODUCTION: Extracorporeal shock wave therapy is very widely used for the
      management of tendinopathies and plantar fasciitis. AIM: The aim of the study is
      to determine whether there are prognostic factors that may influence the outcome
      of extracorporeal shock wave therapy for these diseases. METHODS: Three hundred
      fifty-five patients were analyzed 2 months after shock wave treatment for rotator
      cuff tendinitis, epicondylitis, Achilles tendinopathy, trocanteritis, jumper's
      knee or plantar fasciitis. We recorded the epidemiological, clinical and
      treatment protocol, and these data were correlated with treatment outcome.
      RESULTS: Clinical improvement was achieved in 45.9 % of these patients. We
      discovered that laterality different to the dominant limb (p < 0.0001) and
      repeated shock wave treatments (p = 0.004) are prognostic factors in an
      unsuccessful therapy, while being male (p = 0.015) and a high body mass index (p
      = 0.004) are factors for success. We found no differences in relation to age,
      diet, blood type, work or sport activity, presence of co-morbidities, drugs, type
      of tendinopathy, density of energy delivered and other physiotherapy treatment.
      Knowledge of these prognostic factors may lead to improved insight for physicians
      and physiotherapists to predict the extent of the recovery and adjust
      rehabilitation and patient expectations accordingly.

PMID- 25982091
TI  - Processing of semen by density gradient centrifugation selects spermatozoa with
      longer telomeres for assisted reproduction techniques.
AB  - The ends of eukaryotic chromosomes contain specialized chromatin structures
      called telomeres, the length of which plays a key role in early human embryonic
      development. Although the effect of sperm preparation techniques on major sperm
      characteristics, such as concentration, motility and morphology have been
      previously documented, the possible status of telomere length and its relation
      with sperm preparation techniques is not well-known for humans. The aim of this
      study was to investigate the role of density gradient centrifugation in the
      selection of spermatozoa with longer telomeres for use in assisted reproduction
      techniques in 105 samples before and after sperm processing. After density
      gradient centrifugation, the average telomere length of the sperm was
      significantly longer (6.51 +/- 2.54 versus 5.16 +/- 2.29, P < 0.01), the average
      motile sperm rate was significantly higher (77.9 +/- 11.8 versus 44.6 +/- 11.2, P
      < 0.01), but average DNA fragmentation rate was significantly lower (11.1 +/- 5.9
      versus 25.9 +/- 12.9, P < 0.01) compared with raw semen. Additionally, telomere
      length was positively correlated with semen sperm count (rs = 0.58; P < 0.01). In
      conclusion, density gradient centrifugation is a useful technique for selection
      of sperm with longer telomeres. 

PMID- 25982092
TI  - Impact of ovarian endometrioma on ovarian responsiveness and IVF: a systematic
      review and meta-analysis.
AB  - In this systematic review and meta-analysis, the effect of ovarian endometrioma
      on ovarian responsiveness to stimulation and on assisted reproduction outcomes
      was evaluated. Nine published studies (1039 cases) were included. The number of
      oocytes retrieved (mean difference [MD] -1.50; 95% CI, -2.84 to -0.15, P = 0.03),
      metaphase II (MII) oocytes retrieved (MD -3.61; 95% CI -4.44 to -2.78, P <
      0.00001) and total embryos formed (MD -0.66; 95% CI -1.13 to -0.18, P = 0.007)
      were significantly lower in women with ovarian endometrioma than the control
      group. Gonadotrophin dose, duration of stimulation, number of good-quality
      embryos, implantation rate, clinical pregnancy rate and live birth rate were
      similar. Comparisons between ovaries with endometriomas and healthy ovaries of
      the same individuals were also made. Number of oocytes retrieved, MII oocytes
      retrieved and total embryos formed were not statistically significantly different
      between the affected ovaries and contralateral normal ovaries. Observational
      studies showed that ovarian endometrioma was associated with fewer oocytes
      retrieved, fewer MII oocytes retrieved and fewer total formed embryos. Clinical
      pregnancy rate and live birth rates were not affected. Intra-patient comparisons
      in women with unilateral endometrioma suggested the number of oocytes retrieved,
      MII oocytes retrieved and total embryos formed were similar. 

PMID- 25982093
TI  - The impact of food intake and social habits on embryo quality and the likelihood
      of blastocyst formation.
AB  - The aim of this study was to evaluate the influence of patients' lifestyle
      factors and eating habits on embryo development. A total of 2659 embryos
      recovered from 269 patients undergoing intracytoplasmic sperm injection cycles
      were included. The frequency of intake of food items and social habits were
      registered and its influences on embryo development evaluated. The consumption of
      cereals, vegetables and fruits positively influenced the embryo quality at the
      cleavage stage. The quality of the embryo at the cleavage stage was also
      negatively correlated with the consumption of alcoholic drinks and smoking
      habits. The consumption of fruits influenced the likelihood of blastocyst
      formation, which was also positively affected by the consumption of fish. Being
      on a weight-loss diet and consumption of red meat had a negative influence on the
      likelihood of blastocyst formation. The likelihood of blastocyst formation was
      also negatively influenced by the consumption of alcoholic drinks and by smoking
      habits. The consumption of red meat and body mass index had a negative effect on
      the implantation rate and the likelihood of pregnancy. In addition, being on a
      weight-loss diet had a negative influence on implantation rate. Our evidence
      suggests a possible relationship between environmental factors and ovary biology.

PMID- 25982094
TI  - Effect of embryo freezing on perinatal outcome after assisted reproduction
      techniques: lessons from the Latin American Registry of Assisted Reproduction.
AB  - Embryo cryopreservation is an integral part of assisted reproduction techniques;
      it allows the sequential transfer of all embryos, thus diminishing the risk of
      multiple pregnancies and associated perinatal complications. To address concerns
      about the safety of this procedure, neonatal outcome after 43,070 fresh embryo
      transfers was compared with 12,068 frozen-thawed embryo transfers (FET). After
      adjusting for maternal age, gestational age, embryo development at time of
      transfer, number of babies born and gestational order, FET was not found to be
      associated with an increase in perinatal mortality (odds ratio [OR] 1.72, 95%
      confidence interval [CI] 0.81 to 3.62); preterm birth (OR 1.05, 95% CI 0.93 to
      1.18); or extreme preterm birth (OR 0.82, 95% CI 0.64 to 1.06). Furthermore,
      after correcting for known confounding factors, FET was found to be associated
      with an increase in neonatal weight of 39.7 g (95% CI 1.54 to 64.10; P < 0.0001).
      Embryo cryopreservation was, therefore, not associated with an increase in the
      risk of poor perinatal outcome. 

PMID- 25982095
TI  - Live births in women with recurrent hydatidiform mole and two NLRP7 mutations.
AB  - Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic
      development and excessive proliferation of the trophoblast. Recessive mutations
      in NLRP7 are responsible for recurrent HM (RHM). Women with recessive NLRP7
      mutations fail to have normal pregnancies from spontaneous conceptions with the
      exception of three out of 131 reported patients. Because there is no treatment
      for RHM and maternal-effect genes are needed in the oocytes to sustain normal
      embryonic development until the activation of the embryonic genome, one patient
      with recessive NLRP7 mutations tried ovum donation and achieved a successful
      pregnancy. This study reports three additional live births from donated ova to
      two patients with recessive NLRP7 mutations. The occurrence of two live births
      from spontaneous conceptions to two other patients is also reported. The
      reproductive outcomes and mutations of all reported patients were reviewed and it
      was found that live births are associated with some missense mutations expected
      to have mild functional consequences on the protein. The data support a previous
      observation that ovum donation appears the best management option for these
      patients to achieve normal pregnancies and provide an explanation for the rare
      occurrence of live births from natural spontaneous conceptions in patients with
      two NLRP7 mutations. 

PMID- 25982096
TI  - Homocysteine facilitates LOX-1 activation and endothelial death through the
      PKCbeta and SIRT1/HSF1 mechanism: relevance to human hyperhomocysteinaemia.
AB  - HHcy (hyperhomocysteinaemia) is one of the major risk factors for cardiovascular
      diseases. A high concentration of Hcy (homocysteine) induces endothelial
      dysfunction by activating endothelial oxidative stress. LOX-1 (lectin-like
      oxidized low-density lipoprotein receptor 1) plays a vital role in regulating the
      progression of atherosclerotic lesions. LOX-1 activation causes endothelial
      apoptosis and inflammation. The mechanism is still unclear as to whether Hcy
      affects human endothelial LOX-1 expression. LOX-1 expression level was confirmed
      by Western blotting assay in Hcy-treated endothelial cells. L-Methionine was used
      for HHcy induction in animals. Our results suggested that Hcy increased PKCbeta
      (protein kinase Cbeta) activation to enhance the LOX-1 expression level. The up
      regulation of PKCbeta phosphorylation subsequently causes ROS (reactive oxygen
      species) formation and SIRT1 (sirtuin 1) degradation through a proteasome
      dependent mechanism, thereby mitigating the activity of SIRT1 by deacetylating
      HSF1 (heat-shock transcription factor 1). We also found that NOX2 is a key NAPDH
      oxidase isoform responsible for the Hcy-caused ROS formation. The overexpression
      of SIRT1 and HSF1 reduced the Hcy-induced LOX-1 activation. Silencing PKCbeta
      function also reduced LOX-1 activation and endothelial apoptosis caused by Hcy.
      Our hypothesis was supported by analysing the data from methionine-induced HHcy
      affected animals. Our data indicate a new direction for LOX-1 regulation by the
      modulation of the PKCbeta/NAPDH oxidase/SIRT1/HSF1 mechanism. Our findings might
      provide a novel route for developing new therapeutic treatments for HHcy. 

PMID- 25982097
TI  - The exaggerated inflammatory response in Behcet's syndrome: identification of
      dysfunctional post-transcriptional regulation of the IFN-gamma/CXCL10 IP-10
      pathway.
AB  - The mechanisms underlying the exaggerated inflammatory response in Behcet's
      syndrome (BS) remain poorly understood. We investigated the response of CD14(+)
      blood monocytes to interferon (IFN)-gamma, focusing on the chemokine CXCL10.
      Chemokine synthesis and release were analysed at a protein and mRNA level
      following stimulation with IFN-gamma. Findings in BS patients were compared with
      25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus
      erythematosus (SLE) disease control patients. BS monocytes produced significantly
      more CXCL10 protein than HC monocytes from 2 h following IFN-gamma stimulation,
      despite equivalent quantities of mRNA, suggesting more efficient translation.
      This was significantly more pronounced in BS with high disease activity and in
      those with ocular and neurological clinical manifestations. The imbalance between
      CXCL10 protein and mRNA expression was not observed in either RA or SLE patients,
      and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2).
      Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not
      show abnormal tumour necrosis factor (TNF)-alpha release. Sucrose density
      gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated
      RNA showed equal proportions in BS and HC samples, suggesting that the difference
      between BS and HC may be due to reduced negative control of CXCL10 translation in
      BS at a post-initiation level. We conclude that BS monocytes have dysfunctional
      post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of
      CXCL10 protein upon IFN-gamma stimulation. As CXCL10 is a chemokine that recruits
      mononuclear cells, this abnormality may contribute to the exaggerated
      inflammatory responses that characterizes BS. 

PMID- 25982098
TI  - Digital slide viewing for primary reporting in gastrointestinal pathology: a
      validation study.
AB  - Despite the increasing availability of digital slide viewing, and numerous
      advantages associated with its application, a lack of quality validation studies
      is amongst the reasons for poor uptake in routine practice. This study evaluated
      primary digital pathology reporting in the setting of routine subspecialist
      gastrointestinal pathology, commonplace in most tissue pathology laboratories and
      representing one of the highest volume specialties in most laboratories.
      Individual digital and glass slide diagnoses were compared amongst three
      pathologists reporting in a gastrointestinal subspecialty team, in a prospective
      series of 100 consecutive diagnostic cases from routine practice in a large
      teaching hospital laboratory. The study included a washout period of at least 6
      months. Discordant diagnoses were classified, and the study evaluated against
      recent College of American Pathologists (CAP) recommendations for evaluating
      digital pathology systems for diagnostic use. The study design met all 12 of the
      CAP recommendations. The 100 study cases generated 300 pairs of diagnoses,
      comprising 100 glass slide diagnoses and 100 digital diagnoses from each of the
      three study pathologists. 286 of 300 pairs of diagnoses were concordant,
      representing intraobserver concordance of 95.3 %, broadly comparable to rates
      previously published in this field. In ten of the 14 discordant pairs, the glass
      slide diagnosis was favoured; in four cases, the digital diagnosis was favoured,
      but importantly, the 14 discordant intraobserver diagnoses were considered to be
      of minor clinical significance. Interobserver, or viewing modality independent,
      concordance was found in 94 of the total of 100 study cases, providing a
      comparable baseline discordance rate expected in any second viewing of pathology
      material. These overall results support the safe use of digital pathology in
      primary diagnostic reporting in this setting.

PMID- 25982099
TI  - The antimetastatic drug NAMI-A potentiates the phenylephrine-induced contraction
      of aortic smooth muscle cells and induces a transient increase in systolic blood
      pressure.
AB  - The ruthenium-based drug imidazolium trans
      imidazoledimethylsulphoxidetetrachlorido ruthenate (NAMI-A) is a novel antitumour
      drug under clinical evaluation. In this study, NAMI-A is tested on aortic rings
      in vitro and on the systolic blood pressure in vivo with the aim of evaluating
      its effects on smooth muscle cells and, more in general, on the vascular system.
      Pre-incubation of aortic rings with 10 uM NAMI-A for 10 min potentiates the
      contraction induced by phenylephrine (PE). The reduction of the B max value of
      [(3)H]-prazosin bound to NAMI-A-treated aortic rings and the ability of NAMI-A to
      displace [(3)H]-prazosin and [(3)H]-IP3 binding by 25 and 42%, respectively,
      suggest the involvement of alpha1-adrenoceptor in mediating the effects on smooth
      muscle cells. NAMI-A also decreases the number of maximal sites of [(3)H]
      prazosin bound to kidney membrane preparation from 34 to 24 fmol/mg proteins. A
      single i.p. dose (105 mg/kg) or a repeated treatment for 6 consecutive days (17
      mg/kg/day) in Wistar rats increases the systolic blood pressure, respectively, 1
      h and 3 days after treatment, and the responsiveness of rat aortic rings to PE.
      Atomic absorption spectroscopy confirms the presence of ruthenium in the aortic
      rings excised from the treated rats. These findings suggest monitoring the
      cardiovascular parameters when the drug is used in humans for treating cancer
      patients, particularly if the drug is associated with chemicals that are
      potentially active at the cardiovascular level.

PMID- 25982102
TI  - Phase stability and Raman vibration of the molybdenum ditelluride (MoTe2)
      monolayer.
AB  - The phase stability and phase transition of transition metal dichalcogenide (TMD)
      monolayer materials have attracted tremendous attention due to their attractive
      diverse potential applications. Here, first-principles calculations based on
      density-functional theory are carried out to study the newly synthesized MoTe2
      monolayer. A phase different from the semiconducting trigonal prismatic structure
      and octahedral coordinated structure is found to be stable at room temperature in
      a free standing state, as evidenced by phonon spectrum analysis and molecular
      dynamic simulation. Raman vibrations of all the possible phases are calculated to
      provide additional information for the distinction of different phases in the
      experiment. 

PMID- 25982100
TI  - Insights into the structure-activity relationships of chiral 1,2
      diaminophenylalkane platinum(II) anticancer derivatives.
AB  - The structure-activity relationships of chiral 1,2-diaminophenylalkane
      platinum(II) anticancer derivatives are studied, including interactions with
      telomeric- and genomic-like DNA sequences, the pKa of their diaqua species,
      structural properties obtained from DFT calculations and resonant X-ray emission
      spectroscopy. The binding modes of the compounds to telomeric sequences were
      elucidated, showing no major differences with conventional cis-platinum(II)
      complexes like cisplatin, supporting that the cis-square planar geometry governs
      the binding of small Pt(II) complexes to G4 structures. Double-stranded DNA
      platination kinetics and acid-base constants of the diaqua species of the
      compounds were measured and compared, highlighting a strong steric dependence of
      the DNA-binding kinetics, but independent to stereoisomerism. Structural features
      of the compounds are discussed on the basis of dispersion-corrected DFT, showing
      that the most active series presents conformers for which the platinum atom is
      well devoid of steric hindrance. If reactivity indices derived from conceptual
      DFT do not show evidences for different reactivity between the compounds, RXES
      experiments provide new insight into the availability of platinum orbitals for
      binding to nucleophiles. 

PMID- 25982101
TI  - Low-energy Resistive Random Access Memory Devices with No Need for a Compliance
      Current.
AB  - A novel resistive random access memory device is designed with SrTiO3/
      La2/3Sr1/3MnO3 (LSMO)/MgAl2O4 (MAO)/Cu structure, in which metallic epitaxial
      LSMO is employed as the bottom electrode rather than traditional metal materials.
      In this device, the critical external compliance current is no longer necessary
      due to the high self-resistance of LSMO. The LMSO bottom electrode can act as a
      series resistor to offer a compliance current during the set process. Besides,
      the device also has excellent switching features which are originated in the
      formation of Cu filaments under external voltage. Therefore it provides the
      possibility of reducing power consumption and accelerating the commercialization
      of resistive switching devices. 

PMID- 25982103
TI  - Correction: Synthesis-atomic structure-properties relationships in metallic
      nanoparticles by total scattering experiments and 3D computer simulations: case
      of Pt-Ru nanoalloy catalysts.

PMID- 25982104
TI  - Do asymptomatic patients have normal function after percutaneous fixation of the
      posterior pelvic ring? A case-control pilot study.
AB  - BACKGROUND: Following treatment of a posterior pelvic disruption, residual
      deformity or associated injuries can adversely affect functional recovery. No
      study has been performed on gait and functional outcome after closed reduction
      and percutaneous screw fixation (CRPSF) of posterior pelvic disruption in
      clinically asymptomatic patients. The purpose of this study was to determine if
      gait and functional outcome are different from normal in asymptomatic patients
      with a posterior pelvic injury after CRPSF, serving as a pilot study in this
      regard. METHODS: Six asymptomatic patients with no grossly evident gait
      abnormality, treated by CRPSF for a posterior pelvic disruption, were included in
      the study (SG). A control group (CG) of six healthy volunteers was created. All
      participants completed the 12-Item Short Form Health Survey version 2 (SF-12v2),
      the Majeed Pelvic Score (MPS), and the Iowa Pelvic Score (IPS). In addition, the
      participants' gait was analyzed. RESULTS: Pelvic drop was significantly smaller
      on the uninjured side in the SG when compared to the injured side in the SG.
      There was no significant difference between the injured and uninjured side for
      other gait parameters within the SG. Knee angle at initial contact was
      significantly greater on the injured side when compared to the CG. The SG scored
      statistically worse than the CG on the Physical Component Summary part of the SF
      12v2. However, when evaluated by age group using national mean scores, the SG
      differences were minimal. All six patients in our study scored "excellent" on
      both MPS and IPS. CONCLUSIONS: Despite having subclinical alterations in gait,
      asymptomatic pelvic ring injured patients show minimal, if any, evidence of
      impaired functional outcome following successful reduction of a posterior pelvic
      disruption treated by CRPSF.

PMID- 25982105
TI  - Rhodium(I)-Catalyzed Sequential C(sp)-C(sp(3)) and C(sp(3))-C(sp(3)) Bond
      Formation through Migratory Carbene Insertion.
AB  - A Rh(I)-catalyzed three-component reaction of tert-propargyl alcohol, diazoester,
      and alkyl halide has been developed. This reaction can be considered as a carbene
      involving sequential alkyl and alkynyl coupling, in which C(sp)-C(sp(3)) and
      C(sp(3))-C(sp(3)) bonds are built successively on the carbenic carbon atom. The
      Rh(I)-carbene migratory insertion of an alkynyl moiety and subsequent alkylation
      are proposed to account for the two separate C-C bond formations. This reaction
      provides an efficient and tunable method for the construction of all-carbon
      quaternary center.

PMID- 25982106
TI  - Cardiac Resynchronization Therapy in the Autumn of Life.

PMID- 25982107
TI  - Predict, Protect, Prevent: Working Toward a Personalized Approach to Heart
      Failure Prevention.

PMID- 25982108
TI  - Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced
      Ejection Fraction.
AB  - OBJECTIVES: The objective of this clinical trial was to assess the safety and
      efficacy of carotid BAT in advanced HF. BACKGROUND: Increased sympathetic and
      decreased parasympathetic activity contribute to heart failure (HF) symptoms and
      disease progression. Baroreflex activation therapy (BAT) results in centrally
      mediated reduction of sympathetic outflow and increased parasympathetic activity.
      METHODS: Patients with New York Heart Association (NYHA) functional class III HF
      and ejection fractions <=35% on chronic stable guideline-directed medical therapy
      (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They
      were randomly assigned to receive ongoing GDMT alone (control group) or ongoing
      GDMT plus BAT (treatment group) for 6 months. The primary safety end point was
      system- and procedure-related major adverse neurological and cardiovascular
      events. The primary efficacy end points were changes in NYHA functional class,
      quality-of-life score, and 6-minute hall walk distance. RESULTS: One hundred
      forty-six patients were randomized, 70 to control and 76 to treatment. The major
      adverse neurological and cardiovascular event-free rate was 97.2% (lower 95%
      confidence bound 91.4%). Patients assigned to BAT, compared with control group
      patients, experienced improvements in the distance walked in 6 min (59.6 +/- 14 m
      vs. 1.5 +/- 13.2 m; p = 0.004), quality-of-life score (-17.4 +/- 2.8 points vs.
      2.1 +/- 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for
      change in distribution). BAT significantly reduced N-terminal pro-brain
      natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days
      hospitalized for HF (p = 0.08). CONCLUSIONS: BAT is safe and improves functional
      status, quality of life, exercise capacity, N-terminal pro-brain natriuretic
      peptide, and possibly the burden of heart failure hospitalizations in patients
      with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the
      Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart
      Failure] Study; NCT01720160).

PMID- 25982109
TI  - Does Age Influence Cardiac Resynchronization Therapy Use and Outcome?
AB  - OBJECTIVES: This study sought to describe the use of CRT-D and its association
      with survival for older patients. BACKGROUND: Many patients who receive cardiac
      resynchronization therapy with defibrillator (CRT-D) in practice are older than
      those included in clinical trials. METHODS: We identified patients undergoing ICD
      implantation in the National Cardiovascular Disease Registry (NCDR) ICD registry
      from 2006 to 2009, who also met clinical trial criteria for CRT, including left
      ventricular ejection fraction (LVEF) <=35%, QRS >=120 ms, and New York Heart
      Association (NYHA) functional class III or IV. NCDR registry data were linked to
      the social security death index to determine the primary outcome of time to death
      from any cause. We identified 70,854 patients from 1,187 facilities who met prior
      trial criteria for CRT-D. The mean age of the 58,147 patients receiving CRT-D was
      69.4 years with 6.4% of patients age 85 or older. CRT use was 80% or higher among
      candidates in all age groups. Follow-up was available for 42,285 patients age
      >=65 years at 12 months. RESULTS: Receipt of CRT-D was associated with better
      survival at 1 year (82.1% vs. 77.1%, respectively) and 4 years (54.0% vs. 46.2% ,
      respectively) than in those receiving only an ICD (p < 0.001). The CRT
      association with improved survival was not different for different age groups (p
      = 0.86 for interaction). CONCLUSIONS: More than 80% of older patients undergoing
      ICD implantation who were candidates for a CRT-D received the combined device.
      Mortality in older patients undergoing ICD implantation was high but was lower
      for those receiving CRT-D.

PMID- 25982110
TI  - The Hospitalization Burden and Post-Hospitalization Mortality Risk in Heart
      Failure With Preserved Ejection Fraction: Results From the I-PRESERVE Trial
      (Irbesartan in Heart Failure and Preserved Ejection Fraction).
AB  - OBJECTIVES: The aim of this study was to investigate prognosis in patients with
      heart failure (HF) with preserved ejection fraction and the causes of
      hospitalization and post-hospitalization mortality. BACKGROUND: Although
      hospitalizations in patients with HF with preserved ejection fraction are common,
      there are limited data from clinical trials on the causes of admission and the
      influence of hospitalizations on subsequent mortality risk. METHODS: Patients (n
      = 4,128) with New York Heart Association functional class II to IV HF and left
      ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in
      Heart Failure and Preserved Ejection Fraction). A blinded events committee
      adjudicated cardiovascular hospitalizations and all deaths using predefined and
      standardized definitions. The risk for death after HF, any-cause, or non-HF
      hospitalization was assessed using time-dependent Cox proportional hazard models.
      RESULTS: A total of 2,278 patients had 5,863 hospitalizations during the 49
      months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For
      any-cause hospitalizations, 26.5% of patients died during follow-up, with an
      incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an
      adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall,
      53.6% of hospitalizations were classified as cardiovascular and 43.7% as
      noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of
      initial (17.6%) and overall (21.1%) hospitalizations, although, after HF
      hospitalization, a substantially higher proportion of readmissions were due to
      primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41%
      deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs.
      The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57)
      relative to patients who were not hospitalized for HF and was greater in those
      with longer durations of hospitalization. There were 1,593 patients with only non
      HF hospitalizations, 21% of whom died during follow-up, with an incident
      mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25
      (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the
      first 30 days and declined over time for all hospitalization categories. Patients
      not hospitalized for HF or for any cause had observed incident mortality rates of
      3.8 and 1.3 deaths per 100 PYs, respectively. CONCLUSIONS: In I-PRESERVE, HFpEF
      patients hospitalized for any reason, and especially for HF, were at high risk
      for subsequent death, particularly early. The findings support the need for
      careful attention in the post-discharge time period including attention to
      comorbid conditions. Among those hospitalized for HF, the high mortality rate and
      increased proportion of readmissions due to HF (highest during the first 30
      days), suggest that this group would be an appropriate target for investigation
      of new interventions.

PMID- 25982111
TI  - Older Adults, "Malignant" Left Ventricular Hypertrophy, and Associated Cardiac
      Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset
      Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular
      Health Study).
AB  - OBJECTIVES: This study hypothesized that biomarkers of subclinical myocardial
      injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N
      terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart
      failure (HF) risk among older adults with left ventricular hypertrophy (LVH).
      BACKGROUND: The natural history of LVH, an important risk factor for HF, is
      heterogeneous. METHODS: NT-proBNP and hs-cTnT were measured at baseline and after
      2 to 3 years in older adults without prior HF or myocardial infarction in the CHS
      (Cardiovascular Health Study). LVH and left ventricular ejection fraction were
      determined by echocardiography. HF events were adjudicated over a median of 13.1
      years and classified as preserved or reduced left ventricular ejection fraction
      (heart failure with preserved ejection fraction or heart failure with reduced
      ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles,
      and by LVH and longitudinal increase in each biomarker was estimated using Cox
      regression. RESULTS: Prevalence of LVH was 12.5% among 2,347 participants with
      complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8
      fold higher among participants with LVH and in the highest biomarker tertile,
      compared with those with low biomarker levels without LVH (NT-proBNP, hazard
      ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR:
      3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher
      among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43
      to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were
      approximately 3-fold more likely to develop HF, primarily HFrEF, compared with
      those without LVH and with stable biomarkers. CONCLUSIONS: The combination of LVH
      with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase,
      identifies older adults at highest risk for symptomatic HF, especially HFrEF.
      These biomarkers may characterize sub-phenotypes in the transition from LVH to HF
      and suggest modifiable targets for prevention.

PMID- 25982112
TI  - Hospitalizations and Prognosis in Elderly Patients With Heart Failure and
      Preserved Ejection Fraction: Time to Treat the Whole Patient.

PMID- 25982115
TI  - The Ubiquitin Ligase SCF(Ucc1) Acts as a Metabolic Switch for the Glyoxylate
      Cycle.
AB  - Despite the crucial role played by the glyoxylate cycle in the virulence of
      pathogens, seed germination in plants, and sexual development in fungi, we still
      have much to learn about its regulation. Here, we show that a previously
      uncharacterized SCF(Ucc1) ubiquitin ligase mediates proteasomal degradation of
      citrate synthase in the glyoxylate cycle to maintain metabolic homeostasis in
      glucose-grown cells. Conversely, transcription of the F box subunit Ucc1 is
      downregulated in C2-compound-grown cells, which require increased metabolic flux
      for gluconeogenesis. Moreover, in vitro analysis demonstrates that oxaloacetate
      regenerated through the glyoxylate cycle induces a conformational change in
      citrate synthase and inhibits its recognition and ubiquitination by SCF(Ucc1),
      suggesting the existence of an oxaloacetate-dependent positive feedback loop that
      stabilizes citrate synthase. We propose that SCF(Ucc1)-mediated regulation of
      citrate synthase acts as a metabolic switch for the glyoxylate cycle in response
      to changes in carbon source, thereby ensuring metabolic versatility and
      flexibility.

PMID- 25982113
TI  - Structural Basis for Receptor Activity-Modifying Protein-Dependent Selective
      Peptide Recognition by a G Protein-Coupled Receptor.
AB  - Association of receptor activity-modifying proteins (RAMP1-3) with the G protein
      coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective
      recognition of the peptides calcitonin gene-related peptide (CGRP) and
      adrenomedullin (AM) that have diverse functions in the cardiovascular and
      lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown.
      We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound
      CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 A resolutions,
      respectively. The peptides similarly occupy a shared binding site on CLR with
      conformations characterized by a beta-turn structure near their C termini rather
      than the alpha-helical structure common to peptides that bind related GPCRs. The
      RAMPs augment the binding site with distinct contacts to the variable C-terminal
      peptide residues and elicit subtly different CLR conformations. The structures
      and accompanying pharmacology data reveal how a class of accessory membrane
      proteins modulate ligand binding of a GPCR and may inform drug development
      targeting CLR:RAMP complexes.

PMID- 25982114
TI  - BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription
      Factors in Acute Myeloid Leukemia.
AB  - The bromodomain and extraterminal (BET) protein BRD4 is a validated drug target
      in leukemia, yet its regulatory function in this disease is not well understood.
      Here, we show that BRD4 chromatin occupancy in acute myeloid leukemia closely
      correlates with the hematopoietic transcription factors (TFs) PU.1, FLI1, ERG,
      C/EBPalpha, C/EBPbeta, and MYB at nucleosome-depleted enhancer and promoter
      regions. We provide evidence that these TFs, in conjunction with the lysine
      acetyltransferase activity of p300/CBP, facilitate BRD4 recruitment to their
      occupied sites to promote transcriptional activation. Chemical inhibition of BET
      bromodomains was found to suppress the functional output of each hematopoietic
      TF, thereby interfering with essential lineage-specific transcriptional circuits
      in this disease. These findings reveal a chromatin-based signaling cascade
      comprised of hematopoietic TFs, p300/CBP, and BRD4 that supports leukemia
      maintenance and is suppressed by BET bromodomain inhibition.

PMID- 25982116
TI  - A Protein Kinase C Phosphorylation Motif in GLUT1 Affects Glucose Transport and
      is Mutated in GLUT1 Deficiency Syndrome.
AB  - Protein kinase C has been implicated in the phosphorylation of the
      erythrocyte/brain glucose transporter, GLUT1, without a clear understanding of
      the site(s) of phosphorylation and the possible effects on glucose transport.
      Through in vitro kinase assays, mass spectrometry, and phosphospecific
      antibodies, we identify serine 226 in GLUT1 as a PKC phosphorylation site.
      Phosphorylation of S226 is required for the rapid increase in glucose uptake and
      enhanced cell surface localization of GLUT1 induced by the phorbol ester 12-O
      tetradecanoyl-phorbol-13-acetate (TPA). Endogenous GLUT1 is phosphorylated on
      S226 in primary endothelial cells in response to TPA or VEGF. Several naturally
      occurring, pathogenic mutations that cause GLUT1 deficiency syndrome disrupt this
      PKC phosphomotif, impair the phosphorylation of S226 in vitro, and block TPA
      mediated increases in glucose uptake. We demonstrate that the phosphorylation of
      GLUT1 on S226 regulates glucose transport and propose that this modification is
      important in the physiological regulation of glucose transport. 

PMID- 25982117
TI  - A Non-Canonical Function of Gbeta as a Subunit of E3 Ligase in Targeting GRK2
      Ubiquitylation.
AB  - G protein-coupled receptors (GPCRs) comprise the largest family of cell surface
      receptors, regulate a wide range of physiological processes, and are the major
      targets of pharmaceutical drugs. Canonical signaling from GPCRs is relayed to
      intracellular effector proteins by trimeric G proteins, composed of alpha, beta,
      and gamma subunits (Galphabetagamma). Here, we report that G protein beta
      subunits (Gbeta) bind to DDB1 and that Gbeta2 targets GRK2 for ubiquitylation by
      the DDB1-CUL4A-ROC1 ubiquitin ligase. Activation of GPCR results in PKA-mediated
      phosphorylation of DDB1 at Ser645 and its dissociation from Gbeta2, leading to
      increase of GRK2 protein. Deletion of Cul4a results in cardiac hypertrophy in
      male mice that can be partially rescued by the deletion of one Grk2 allele. These
      results reveal a non-canonical function of the Gbeta protein as a ubiquitin
      ligase component and a mechanism of feedback regulation of GPCR signaling. 

PMID- 25982118
TI  - Implication of microRNA deregulation in the response of vertebrates to endocrine
      disrupting chemicals.
AB  - Micro ribonucleic acids (miRNAs) are recently discovered small regulatory
      molecules that control messenger RNA (mRNA) translation in plants and animals and
      have been implicated in a variety of hormone-related physiological pathways.
      Estrogens, thyroid hormones, and gonadotropins are all known to act on miRNA
      abundance to cause major shifts in cellular activity, physiology, and homeostatic
      control mechanisms. Research on cancer biology has also recently considered miRNA
      as therapeutic targets, because the deregulation of specific miRNAs in various
      tissues has been correlated with tumorigenesis and other carcinogenic responses.
      Because many pharmaceuticals are considered to be endocrine-disrupting chemicals
      (EDCs), their effects on miRNAs may be important to our understanding of basic
      physiological control and phenotypic outcomes of wildlife exposed to EDCs.
      Presented is a brief overview of the synthesis, control, and action of miRNAs,
      focusing on endocrine systems. The antidepressant fluoxetine will be used as an
      example for miRNA studies in aquatic species, one of the few examples in
      ecotoxicology. Given the mounting evidence that miRNAs are regulated by hormones,
      a clear need exists to investigate the potential for environmental EDCs to
      deregulate miRNA expression and action.

PMID- 25982119
TI  - Hepatic Vascular Control in Liver Transplant and Application in Gastrointestinal
      Surgery.
AB  - Complete control of the hepatic vasculature is routine during liver
      transplantation and sometimes required in general surgical cases. Knowledge of
      approach and management to hepatic vasculature control can be lifesaving. This
      article offers our systematic approach to controlling hepatic vasculature, where
      these techniques can be applied in trauma, general surgical, and transplant
      settings. 

PMID- 25982120
TI  - A Simple Method to Evaluate Whether Pancreas Texture Can Be Used to Predict
      Pancreatic Fistula Risk After Pancreatoduodenectomy.
AB  - INTRODUCTION: Soft pancreas is one of the most important risk factor for
      postoperative pancreatic fistula after pancreatoduodenectomy. The aim of this
      study is to investigate whether pancreatic attenuation index utilized to assess
      the pancreatic texture with computed tomography can be used to predict the risk
      of developing a clinically relevant postoperative pancreatic fistula after
      pancreatoduodenectomy. METHODS: We reviewed 76 consecutive patients undergoing
      pancreatoduodenectomy between 2012 and 2014. The pancreatic attenuation index is
      found by dividing the pancreas density by the spleen density achieved with non
      enhanced computed tomography. The independent predictors of clinically relevant
      postoperative pancreatic fistula were investigated. RESULTS: Clinically relevant
      postoperative pancreatic fistula occurred in 13 patients (17.1%). The group of
      patients with postoperative pancreatic fistula is compared with the group of
      patients without postoperative pancreatic fistula in terms of age, gender, body
      mass index, the American Society of Anesthesiologists (ASA) score, smoking,
      alcohol consumption, medical comorbidities, preoperative biliary drainage, type
      of anastomosis, and pancreatic duct size and pancreatic attenuation index.
      Univariate analyses have shown a significant difference in relation to chronic
      obstructive pulmonary disease and pancreatic attenuation index. The multivariate
      analyses showed that only pancreatic attenuation index was associated with a high
      postoperative pancreatic fistula rate (P = 0.012). CONCLUSION: A preoperative non
      contrast computed tomography scan evaluating pancreatic attenuation index could
      help to predict the occurrence of clinically significant postoperative pancreatic
      fistula after pancreatoduodenectomy.

PMID- 25982121
TI  - Two decades to diagnose bilateral congenital choanal atresia: is this delay
      acceptable?

PMID- 25982122
TI  - Utility of a Paediatric Bleeding Questionnaire as a screening tool for von
      Willebrand disease in apparently healthy children.
AB  - von Willebrand disease (VWD), an inherited bleeding disorder caused by deficiency
      or dysfunction of von Willebrand factor (VWF) is diagnosed when a personal and
      often a family history of excessive mucocutaneous bleeding is present along with
      abnormal laboratory studies. An accurate assessment of haemorrhagic symptoms is
      key in suspecting VWD but presents a challenge especially in children due to
      overlap between normal and abnormal bleeding. Bleeding questionnaire (BQ) scores
      have been validated in adults and have recently been validated in children with
      VWD for assessing bleeding severity. However, there are limited data supporting
      their use prospectively in healthy children with bleeding complaints. AIM: The
      objectives of this study were to obtain normative data from children and validate
      a paediatric BQ (PBQ) to determine the discriminative ability of its total score
      and its individual components for identifying children likely to have VWD.
      METHODS: The PBQ was administered to 1281 multiethnic, healthy children between
      30 days and 18 years of age presenting to a general paediatric office and to 35
      children with VWD based on VWF antigen, activity and multimer pattern. RESULTS:
      When children with total BQ scores of 3 or more were predicted to have VWD, the
      sensitivity was 97.2%, the specificity was 97.1%, the positive predictive value
      was 48.6% and the negative predictive value was 99.9%. CONCLUSIONS: The PBQ may
      help discriminate a significant bleeding history from trivial bleeding, may be
      integrated into the primary care algorithm for evaluating children suspected with
      VWD.

PMID- 25982124
TI  - Generation mean analysis of grain quality traits in selected rice populations
      derived from different amylose characteristics.
AB  - BACKGROUND: Genetic analysis using generation mean analysis is a tool for
      designing the most appropriate breeding approaches to developing varieties of
      rice. It estimates the gene actions that control quantitative traits, as well as
      the additive, dominance and epistatic effects. This study was conducted using
      three rice populations that were derived from parental lines with different
      amylose content. The aim was to partition the gene actions using generation mean
      analysis for the selected populations. RESULTS: A scaling test was carried out to
      evaluate the fulfilment of the additive-dominance model. Non-allelic interaction
      was observed for milled grain length, length-to-width ratio and milled rice
      recovery of all populations evaluated. An additive-dominance model was not
      adequate for amylose, gel consistency, grain length, grain width, milled grain
      width and head rice recovery, thus epistasis was involved in the populations
      evaluated. The importance of additive gene action was observed for grain length,
      milled grain length and milled rice recovery for populations of high- and low
      amylose parents. However, populations with intermediate- and high-amylose parents
      and intermediate- and low-amylose parents shared almost similar dominance gene
      actions for most of the physical grain quality traits. CONCLUSION: These results
      suggested that delayed selection is the best approach for traits governed by
      dominance and epistasis effects. Meanwhile, the traits that were governed by
      additive effects should undergo thorough selection at an early stage.

PMID- 25982123
TI  - Mechanistic studies of the tyrosinase-catalyzed oxidative cyclocondensation of 2
      aminophenol to 2-aminophenoxazin-3-one.
AB  - Tyrosinase (EC 1.14.18.1) catalyzes the monophenolase and diphenolase reaction
      associated with vertebrate pigmentation and fruit/vegetable browning. Tyrosinase
      is an oxygen-dependent, dicopper enzyme that has three states: Emet, Eoxy, and
      Edeoxy. The diphenolase activity can be carried out by both the met and the oxy
      states of the enzyme while neither mono- nor diphenolase activity results from
      the deoxy state. In this study, the oxidative cyclocondensation of 2-aminophenol
      (OAP) to the corresponding 2-aminophenoxazin-3-one (APX) by mushroom tyrosinase
      was investigated. Using a combination of various steady- and pre-steady state
      methodologies, we have investigated the kinetic and chemical mechanism of this
      reaction. The kcat for OAP is 75 +/- 2s(-1), K(OAP)M = 1.8 +/- 0.2mM, K(O2)M =25
      +/- 4 MUM with substrates binding in a steady-state preferred fashion. Stopped
      flow and global analysis support a model where OAP preferentially binds to the
      oxy form over the met (k7 ? k1). For the met form, His269 and His61 are the
      proposed bases, while the oxy form uses the copper-peroxide and His61 for the
      sequential deprotonation of anilinic and phenolic hydrogens. Solvent KIEs show
      proton transfer to be increasingly rate limiting for kcat/K(OAP)M as [O2] -> 0
      MUM (1.38 +/- 0.06) decreasing to 0.83 +/- 0.03 as [O2] -> infinity reflecting a
      partially rate limiting MU-OH bond cleavage (E met) and formation (E oxy)
      following protonation in the transition state. The coupling and cyclization
      reactions of o-quinone imine and OAP pass through a phenyliminocyclohexadione
      intermediate to APX, forming at a rate of 6.91 +/- 0.03 MUM(-1)s(-1) and 2.59E-2
      +/- 5.31E-4s(-1). Differences in reactivity attributed to the anilinic moiety of
      OAP with o-diphenols are discussed.

PMID- 25982125
TI  - Influence of muscle fiber orientation on water and metabolite relaxation times,
      magnetization transfer, and visibility in human skeletal muscle.
AB  - PURPOSE: To gain a deeper understanding of the influence of skeletal muscle fiber
      orientation on metabolite visibility, magnetization transfer from water, and
      water proton relaxation rates in (1)H MR spectra. METHODS: Non-water-suppressed
      MR spectroscopy was performed in tibialis anterior muscle (TA) of 10 healthy
      adults, with the TA oriented either parallel or at the magic angle to the 3T
      field. Spectra were acquired with metabolite-cycled PRESS, and water inversion
      from 50 to 2510 ms before excitation. Water proton T2 relaxation was sampled with
      STEAM with echo times from 12 to 272 ms. RESULTS: Apparent concentrations of
      total creatine (tCr), taurine, and trimethylammonium compounds were reduced by
      29% to 67% when TA was parallel to B0. Both tCr peak areas were strongly
      correlated to the methylene peak splitting. Magnetization transfer rates from
      water to tCr CH3 were not significantly different between orientations. Water T1s
      were similar between orientations, but T2s were statistically significantly
      shorter by 1 ms in the parallel orientation (P = 0.002). CONCLUSION: Muscle
      metabolite visibilities in MR spectroscopy and water T2 times depend
      substantially on muscle fiber orientation relative to B0 . In contrast,
      magnetization transfer rates appear to depend on muscle composition, rather than
      fiber orientation.

PMID- 25982126
TI  - Phytochemical analysis and antioxidant potential of the leaves of Garcinia
      travancorica Bedd.
AB  - Phytochemical analysis of the leaves of Garcinia travancorica, a hitherto
      uninvestigated endemic species to the Western Ghats of south India, resulted in
      isolation and characterisation of the polyisoprenylated benzophenones 7-epi
      nemorosone (1) and garcinol (2) along with biflavonoids GB-1a (3), GB-1 (4), GB-2
      (5), morelloflavone (6) and morelloflavone-7"-O-beta-D-glycoside or fukugiside
      (7). The compounds were identified using various spectroscopic techniques, mainly
      through NMR and MS. The methanol extract and the biflavonoids 3, 4, 5 and 7
      showed potential in vitro antioxidant activities. The IC50 value of the 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of compound 7 was
      8.34 +/- 2.12 MUg/mL, comparable to that of standard ascorbic acid (3.2 +/- 0.50
      MUg/mL). In the superoxide radical scavenging assay, compound 7 gave IC50 value
      of 6.95 +/- 1.33 MUg/mL close to standard ascorbic acid with IC50 value of 5.8 +/
      0.25 MUg/mL. Validated HPTLC estimation revealed G. travancorica as a rich
      source of morelloflavone-7"-O-beta-D-glycoside (7.12% dry wt. leaves).

PMID- 25982127
TI  - Optimal evaluation time point for patch testing to predict skin irritation of
      commercial topical drugs.
AB  - To develop patch testing (PT) that better reflects the skin irritation resulting
      from repeated applications, we methodically classified PT results and examined
      correlations between these results with results from repeated application tests.
      A total of 115 commercial topical drugs were used for patch testing. In two
      groups of 30 healthy individuals with normal back skin, 55 or 60 commercial
      topical drugs were applied to the back for 24 h. Skin reactions were scored for
      each group at 2 and 24 h after patch removal. Based on time-dependent changes in
      skin reaction at each evaluation time, PT results were classified into six
      different types. For repeated application testing, a total of 17 products with
      different types of PT results were selected. A total of 104 healthy individuals
      divided into three groups (n = 22-52 each) received application of 6-7 test
      materials, differing for each group, for 3 weeks on both arms. Incidences of
      positive symptoms induced by repeated drug application excluding transient
      erythema showed a greater correlation with reaction levels at 24 h after patch
      removal than 2 h after patch removal. Many test materials that triggered a high
      incidence of positive symptoms after repeated application also exhibited erythema
      or greater reaction up to 24 h after patch removal. PT offers a useful test
      system for predicting skin irritation that develops after repeated application of
      topical drug. Moreover, assessment at 24 h after patch removal is suggested as
      the optimal evaluation time point to reflect the results of repeated application
      tests. 

PMID- 25982128
TI  - Allelic variants in the PRR37 gene and the human-mediated dispersal and
      diversification of sorghum.
AB  - KEY MESSAGE: Allele phylogenetic analysis of the sorghum flowering-time gene
      PRR37 provided new insight into the human-mediated selection of a key adaptive
      gene that occurred during sorghum's diversification and worldwide dispersal. The
      domestication and spread of the tropical cereal sorghum is associated with the
      historic movement of humans. We show that an allelic series at PRR37 (pseudo
      response regulator 37), a circadian clock-associated transcription factor, was
      selected in long-day ecosystems worldwide to permit floral initiation and grain
      production. We identified a series of loss-of-function (photoperiod-insensitive)
      alleles encoding truncated PRR37 proteins, alleles with key amino acid
      substitutions in the pseudo-receiver domain, and a novel splice variant in which
      the pseudo-receiver domain is truncated. Each PRR37 allelic variant was traced to
      a specific geographic location or specialized agronomic type. We present a
      graphical model that shows evidence of human selection and gene flow of the PRR37
      allelic variants during the global dispersal and agronomic diversification of
      sorghum. With the recent identification of the Ghd7 gene as an important
      regulator of flowering date in sorghum, we briefly examine whether loss-of
      function Ghd7 allelic variants were selected prior to the human-mediated movement
      of sorghum from its equatorial center of origin to temperate climates worldwide.

PMID- 25982129
TI  - Comparative mapping of quantitative trait loci for Fusarium head blight
      resistance and anther retention in the winter wheat population Capo * Arina.
AB  - KEY MESSAGE: Fusarium resistance in Arina is highly quantitative and governed by
      multiple small effect QTL. Anther retention has a high correlation with FHB
      susceptibility and appears a practicable indirect selection target for enhancing
      FHB resistance. The Swiss winter wheat cultivar Arina possesses a high resistance
      level constituted by a number of small to medium effect QTL reported from three
      independent mapping populations. Yet these overlap only for one resistance QTL on
      the long arm of chromosome 1B. The present study characterized Fusarium head
      blight (FHB) resistance in a population of 171 recombinant inbred lines from a
      cross between Arina (resistant) and Capo (moderately resistant). The population
      was evaluated for FHB resistance under field conditions for 3 years.
      Additionally, we phenotyped anther retention, plant height and flowering date to
      analyze their association with resistance. Lines with a low proportion of
      retained anthers after flowering and tall plants were significantly less
      diseased, while flowering date had no association with FHB severity. QTL analysis
      identified eight small to medium effect QTL for FHB severity, of which QTL on
      1BS, 3B, 4AL and 6BL likely correspond to resistance alleles already detected in
      previously studied Arina populations. QTL for anther retention mapped to 4AL, 6BL
      and 5AS. Notably, QTL on 4AL and 6BL overlapped with QTL for FHB severity. A
      single small effect QTL for plant height was detected on 5AS and no QTL was
      identified for flowering date. Genotypes having three or four resistance alleles
      in combination showed a good resistance level, indicating pyramiding resistance
      QTL as a powerful approach for breeding resistant cultivars. Selection for rapid
      and complete anther extrusion appears promising as an indirect selection
      criterion for enhancing FHB resistance.

PMID- 25982131
TI  - Genetic characterization and expression analysis of wheat (Triticum aestivum)
      line 07OR1074 exhibiting very low polyphenol oxidase (PPO) activity.
AB  - KEY MESSAGE: Characterized novel mutations present at Ppo loci account for the
      substantial reduction of the total kernel PPO activity present in a putative null
      Ppo - A1 genetic background. Wheat (Triticum aestivum) polyphenol oxidase (PPO)
      contributes to the time-dependent discoloration of Asian noodles. Wheat contains
      multiple paralogous and orthologous Ppo genes, Ppo-A1, Ppo-D1, Ppo-A2, Ppo-D2,
      and Ppo-B2, expressed in wheat kernels. To date, wheat noodle color improvement
      efforts have focused on breeding cultivars containing Ppo-D1 and Ppo-A1 alleles
      conferring reduced PPO activity. A major impediment to wheat quality improvement
      is a lack of additional Ppo alleles conferring reduced kernel PPO. In this study,
      a previously reported very low PPO line, 07OR1074, was found to contain a novel
      allele at Ppo-A2 and null alleles at the Ppo-A1 and Ppo-D1 loci. To examine the
      impact of each mutation upon kernel PPO, populations were generated from crosses
      between 07OR1074 and the hard white spring wheat cultivars Choteau and Vida.
      Expression analysis using RNA-seq demonstrated no detectable Ppo-A1 transcripts
      in 07OR1074 while Ppo-D1 transcripts were present at less than 10% of that seen
      in Choteau and Vida. Novel markers specific for the Ppo-D1 and Ppo-A2 mutations
      discovered in 07OR1074, along with the Ppo-A1 STS marker, were used to screen
      segregating populations. Evaluation of lines indicated a substantial genotypic
      effect on PPO with Ppo-A1 and Ppo-D1 alleles contributing significantly to total
      PPO in both populations. These results show that the novel mutations in Ppo-A1
      and Ppo-D1 present in 07OR1074 are both important to lowering overall wheat seed
      PPO activity and may be useful to produce more desirable and marketable wheat
      based products.

PMID- 25982130
TI  - A QTL with major effect on reducing leaf rust severity on the short arm of
      chromosome 1A of wheat detected across different genetic backgrounds and diverse
      environments.
AB  - KEY MESSAGE: Selection for QLr.cau - 1AS (a major QTL detected in wheat for
      reducing leaf rust severity) based on the DNA marker gpw2246 was as effective as
      selection for Lr34 based on cssfr5. Leaf rust is an important disease of wheat
      worldwide. Utilization of slow-rusting resistance constitutes a strategy to
      sustainably control this disease. The American wheat cultivar Luke exhibits slow
      leaf-rusting resistance at the adult plant stage. The objectives of this study
      were to detect and validate QTL for the resistance in Luke. Three winter wheat
      populations were used, namely, 149 recombinant inbred lines (RILs) derived from
      the cross Luke * Aquileja, 307 RILs from Luke * AQ24788-83, and 80 F2:3 families
      selected from Lingxing66 * KA298. Aquileja and Lingxing66 are highly susceptible
      to leaf rust. AQ24788-83 shows high (susceptible) infection type but contains the
      slow-rusting gene Lr34 as diagnosed by the gene-specific marker cssfr5. KA298, an
      F9 RIL selected from Luke * AQ24788-83, contains Lr34 and QLr.cau-1AS (a major
      QTL originated from Luke, this study). These wheats were evaluated for leaf rust
      in 12 field and greenhouse environments involving four locations and five
      seasons. Genotyping was done using simple sequence repeat (SSR) and diversity
      arrays technology markers. Of the detected QTLs, QLr.cau-1AS was significant
      consistently across all the genetic backgrounds, test environments, and likely a
      wide range of pathogen races. QLr.cau-1AS explained 22.3-55.2% of leaf rust
      phenotypic variation, being comparable to Lr34 in effect size. A co-dominant SSR
      marker (gpw2246, http://wheat.pw.usda.gov/GG2/index.shtml ) was identified to be
      tightly linked to QLr.cau-1AS. Selection based on gpw2246 for QLr.cau-1AS was as
      effective as the selection based on cssfr5 for Lr34. QLr.cau-1AS will be helpful
      for increasing the genetic diversity of slow leaf-rusting resistance in wheat
      breeding programs.

PMID- 25982132
TI  - Stability and genetic control of morphological, biomass and biofuel traits under
      temperate maritime and continental conditions in sweet sorghum (Sorghum
      bicolour).
AB  - KEY MESSAGE: Eight morphological, biomass and biofuel traits were found with high
      broad-sense heritability and 18 significant QTLs discovered including one locus
      controlling the stem juice trait for sorghum grown in Denmark and China. Sweet
      sorghum with tall plant, fast maturation and high stem Brix content can be bred
      as a biofuel crop for Northern Europe. Sweet sorghum (Sorghum bicolour), a native
      tropical C4 crop, has attracted interest as a bioenergy crop in northern
      countries due to its juice-rich stem and high biomass production. Little is known
      about the traits important for its adaptation to high altitude climatic
      conditions and their genetic controls. Recombinant inbred lines derived from a
      cross between a sweet and a grain kaoliang sorghum were used in five field trials
      in Denmark and in China to identify the stability and genetic controls of
      morphological, biomass and biofuel traits during three consecutive summers with
      short duration, cool temperatures and long days. Eight out of 15 traits were
      found with high broad-sense heritability. Strong positive correlations between
      plant height and biomass traits were observed, while Brix and juice content were
      under different genetic controls. Using newly developed PAV (presence and absence
      variant) markers, 53 QTLs were detected, of which 18 were common for both
      countries, including a locus controlling stem juice (LOD score = 20.5, r (2) =
      37.5 %). In Denmark, the heading stage correlated significantly with biomass and
      morphology traits, and two significant maturity QTLs detected on chromosomes
      SBI01 and SBI02 co-localised with QTLs previously associated with early-stage
      chilling tolerance, suggesting that accelerating maturation might be a means of
      coping with low-temperature stress. Our results suggest that selection for tall
      and fast maturating sorghum plants combined with high Brix content represents a
      high potential for breeding bioenergy crop for Northern Europe.

PMID- 25982133
TI  - Effect of subanaesthetic ketamine on plasma and saliva cortisol secretion.
AB  - BACKGROUND: The commonality between chronic conditions that are treated with low
      dose ketamine, such as specific chronic pain conditions, depression, and post
      traumatic stress disorder, can be found in relation to the stress system,
      particularly the hypothalamus-pituitary-adrenal axis. In this study we assess the
      effect of ketamine on the stress system by measuring plasma and saliva cortisol
      production during and following exposure to low-dose ketamine. METHODS: In a
      double-blind, randomized, placebo-controlled study, the influence of
      subanaesthetic ketamine (0.29 mg kg(-1) h(-1) for 1 h, followed by 0.57 mg kg(-1)
      h(-1) for another hour) was studied with repeated plasma and saliva cortisol
      samples in 12 healthy male volunteers. A pharmacokinetic-pharmacodynamic model
      was used to describe the circadian rhythm-dependent ketamine-induced production
      of cortisol. RESULTS: The endogenous mean baseline cortisol production was 7.9
      (SE 1.5) nM min(-1). Consistent with the circadian rhythm, cortisol production
      decayed by 1.25 nM min(-1) h(-1). Ketamine doubled the cortisol production at a
      concentration of 165 (SE 35) ng ml(-1). The salivary cortisol concentration
      closely mirrored the plasma concentration and was exponentially related to the
      plasma concentration with, at 100 ng ml(-1) ketamine, a saliva:plasma ratio of
      0.036 (se 0.006). CONCLUSIONS: Ketamine has an appreciable effect on cortisol
      production. This may impact on critical physiological and psychological
      functions. CLINICAL TRIAL REGISTRATION: This study was registered in the Dutch
      Trial Register under number NTR2717 at www.trialregister.nl.

PMID- 25982134
TI  - Higher fibrinogen concentrations for reduction of transfusion requirements during
      major paediatric surgery: A prospective randomised controlled trial.
AB  - BACKGROUND: Hypofibrinogenaemia is one of the main reasons for development of
      perioperative coagulopathy during major paediatric surgery. The aim of this study
      was to assess whether prophylactic maintenance of higher fibrinogen
      concentrations through administration of fibrinogen concentrate would decrease
      the volume of transfused red blood cell (RBCs). METHODS: In this prospective,
      randomised, clinical trial, patients aged 6 months to 17 yr undergoing
      craniosynostosis and scoliosis surgery received fibrinogen concentrate (30 mg kg(
      1)) at two predefined intraoperative fibrinogen concentrations [ROTEM((r)) FIBTEM
      maximum clot firmness (MCF) of <8 mm (conventional) or <13 mm (early
      substitution)]. Total volume of transfused RBCs was recorded over 24 h after
      start of surgery. RESULTS: Thirty children who underwent craniosynostosis surgery
      and 19 children who underwent scoliosis surgery were treated per protocol. During
      craniosynostosis surgery, children in the early substitution group received
      significantly less RBCs (median, 28 ml kg(-1); IQR, 21 to 50 ml kg(-1)) compared
      with the conventional fibrinogen trigger of <8 mm (median, 56 ml kg(-1); IQR, 28
      to 62 ml kg(-1)) (P=0.03). Calculated blood loss as per cent of estimated total
      blood volume decreased from a median of 160% (IQR, 110-190%) to a median of 90%
      (IQR, 78-110%) (P=0.017). No significant changes were observed in the scoliosis
      surgery population. No bleeding events requiring surgical intervention,
      postoperative transfusions of RBCs, or treatment-related adverse events were
      observed. CONCLUSIONS: Intraoperative administration of fibrinogen concentrate
      using a FIBTEM MCF trigger level of <13 mm can be successfully used to
      significantly decrease bleeding, and transfusion requirements in the setting of
      craniosynostosis surgery, but not scoliosis. CLINICAL TRIAL REGISTRY NUMBER:
      ClinicalTrials.gov NCT01487837.

PMID- 25982135
TI  - Clinical features and induction outcome of childhood acute lymphoblastic leukemia
      in a lower/middle income population: A multi-institutional report from Pakistan.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer of
      childhood. Some evidence suggests differences in clinical and cytogenetic
      characteristics of ALL based on geographic and ethnic variations. However, data
      on ALL characteristics and early outcome of therapy from low/middle-income
      countries such as Pakistan are scanty. PROCEDURE: A prospective, multi
      institutional cohort study in Karachi enrolled 646 newly diagnosed children with
      ALL over 3 years. Standard forms were used to collect demographic, clinical, and
      laboratory data at presentation and at the end of induction. RESULTS: Of the
      total, 66.1% (n = 427) were males. Median age was 6 (mean +/- SE 6.87 +/- 0.16;
      range 0.16-18) years. The most common clinical presentation was fever (88.7%).
      BPC-ALL was diagnosed in 78.5%, while 17.5% had T-ALL; 28.8% had a WBC >50 *
      10(9) /L. With 316 patients karyotyped, hypodiploidy and hyperdiploidy were seen
      in 5.1% and 10.7%, respectively. Of those tested, ETV6-RUNX1 translocation was
      detected in 13.2%, while BCR-ABL1 translocation and MLL gene rearrangements were
      seen in 7.3% and 4.6%, respectively. The cumulative loss to follow up before and
      during induction was 12.8% (n = 83) and 11.5% (n = 74) died before or during this
      phase. Induction was successfully completed by only 75.6% (n = 489) of the entire
      cohort and 69.6% (n = 450) achieved remission. CONCLUSION: These patients had ALL
      with higher risk features than that reported from developed countries. One
      quarter failed to complete induction chemotherapy. This suboptimal result
      requires further study and development of innovative interventions, particularly
      focusing on the causes and solutions for late referral, abandonment, and
      infections.

PMID- 25982136
TI  - Effects of ivabradine on cardiac electrophysiology in dogs with age-related
      atrial fibrillation.
AB  - BACKGROUND: Ivabradine is an inhibitor of mixed Na+-K+ current that could combine
      with HCN channels to reduce the transmembrane velocity of funny current (If),
      heart rate, and cardiac efficiency, and thus be used for the treatment of
      cardiovascular diseases such as chronic heart failure. As an ion channel blocker,
      Ivabradine is also a potential antiarrhythmic agent. MATERIAL/METHODS: Twelve
      aging dogs (8-10 years old) underwent rapid atrial pacing for 2 months to induce
      age-related AF in this study. The dogs were randomly divided into the Ivabradine
      group and aging-AF group. The effects of Ivabradine on the electrophysiological
      parameters, including the effective refractory period (ERP) of the pulmonary
      veins and atrium, duration of AF, and inducing rate of AF, were investigated.
      RESULTS: As compared to the aging-AF group, the ERPs of the left superior
      pulmonary vein (139.00+/-4.18 ms vs. 129.00+/-4.08 ms, P=0.005) and left auricle
      (135.00+/-3.53 ms vs. 122.00+/-4.47 ms, P=0.001) were significantly increased,
      while the duration of AF (46.60+/-5.07 s vs. 205.40+/-1.14 s, P=0.001) and
      inducing rate of AF (25% vs. 60%, P=0.001) were significantly decreased.
      CONCLUSIONS: Ivabradine could effectively reduce the inducing rate of AF, and
      thus be used as an upstream drug for the prevention of age-related AF.

PMID- 25982137
TI  - Establishment of evanescent wave fiber-optic immunosensor method for detection
      bluetongue virus.
AB  - The evanescent wave fiber immunosensors (EWFI) technique was developed for the
      real-time rapidly sensitive and specific detection of the monoclonal antibody 3E2
      of BTV. The outer-core protein VP7 of BTV was labled on the surface of the
      exposed fiber-optic core. The monoclonal antibody 3E2 of BTV VP7 were added and
      then the goat ant-rat IgG conjugated with Cy3 was captured. After the 532nm pulse
      (excitation source) reached the fiber probe, evanescent wave was generated, which
      excited the Cy3 bound to the immuno-complex and produced the fluorescent signal,
      which was changed into electrical signals read through computer. The preliminary
      results suggested that a detection limit of 10ng/ml was measured for the
      monoclonal antibody 3E2, which is equal to the sensitivity of ELISA. The 3E2
      sample was specifically detected through the EWFI assay in 15min, and the fiber
      can be recycled at least ten times through TEA solution condition. This developed
      EWFI was a real-time rapidly sensitive and specific way for the detection of BTV
      antibodies. 

PMID- 25982138
TI  - The Effect of Caffeine on Diaphragmatic Activity and Tidal Volume in Preterm
      Infants.
AB  - OBJECTIVE: To determine the effect of caffeine on diaphragmatic activity, tidal
      volume (Vt), and end-expiratory lung volume (EELV) in preterm infants. STUDY
      DESIGN: Using transcutaneous electromyography of the diaphragm (dEMG), we
      measured diaphragmatic activity from 30 minutes before (baseline) to 3 hours
      after administration of an intravenous caffeine-base loading dose in 30
      spontaneously breathing preterm infants (mean gestational age, 29.1 +/- 1.3
      weeks), most of whom were on noninvasive respiratory support. Diaphragmatic
      activity was expressed as the percentage change in dEMG amplitude, area under the
      curve, respiratory rate, and inspiratory and expiratory times. Using respiratory
      inductive plethysmography, we measured changes in Vt and EELV from baseline.
      These outcome variables were calculated at 8 fixed time points after caffeine
      administration (5, 15, 30, 60, 90, 120, 150, and 180 minutes) and compared with
      baseline. RESULTS: Caffeine administration resulted in rapid (within 5 minutes)
      increases in dEMG amplitude (median, 43%; IQR, 24%-63%; P < .001) and area under
      the curve (median, 28%; IQR, 14%-48%; P < .001). Vt also increased by a median of
      30% (IQR, 7%-48%), and this change was significantly correlated with the change
      in dEMG amplitude (r = 0.67; P < .001). These effects were relatively stable
      until 120 minutes after caffeine administration. Caffeine did not consistently
      impact EELV, respiratory rate, or inspiratory and expiratory times. CONCLUSION:
      Caffeine treatment results in a rapid and sustained increase in diaphragmatic
      activity and Vt in preterm infants.

PMID- 25982139
TI  - Unmistakable Morphology? Infantile Malignant Osteopetrosis Resembling Juvenile
      Myelomonocytic Leukemia in Infants.
AB  - The initial clinical and hematologic presentation of infantile malignant
      osteopetrosis may be indistinguishable from that of juvenile myelomonocytic
      leukemia in infants. Timely radiographic imaging, however, allows straightforward
      delineation of these 2 severe diseases and facilitates immediate initiation of
      appropriate therapy. 

PMID- 25982140
TI  - Extracorporeal Membrane Oxygenation in Pediatric Trisomy 21: 30 Years of
      Experience from the Extracorporeal Life Support Organization Registry.
AB  - OBJECTIVES: To describe the use of extracorporeal membrane oxygenation (ECMO) in
      patients with trisomy 21 (T21), to identify risk factors for hospital mortality,
      and to compare outcomes with those of patients without T21. STUDY DESIGN:
      Children under age 18 years registered in the Extracorporeal Life Support
      Organization Registry were included. Comparisons between patients with T21 and
      patients without T21 were performed using the chi(2) or Wilcoxon rank-sum test
      and multivariable logistic regression. RESULTS: The study cohort included 623
      patients with T21 and 46 239 patients without T21. The prevalence of T21 was
      13.5/1000 patients receiving ECMO. ECMO utilization in patients with T21
      increased over time, with 60% of cases occurring in the last decade. There was no
      significant difference in survival between patients without T21 and those with
      T21 (63% vs 57%; P = .23). In patients with T21, independent risk factors for
      mortality before cannulation were a cardiac indication for ECMO support and
      milrinone use (P <= .001 for both). Multivariable risk factors for mortality on
      ECMO included hemorrhagic, neurologic, renal, and pulmonary complications (P <
      .04 for all). CONCLUSION: The use of ECMO in patients with T21 has increased over
      time. Patients with a cardiac indication for ECMO have higher mortality compared
      with those supported for respiratory indications. Despite differences in
      indications for ECMO, patients with T21 have similar hospital survival as those
      without T21; thus, by itself, a diagnosis of T21 should not be considered a risk
      factor for in-hospital mortality when contemplating ECMO cannulation.

PMID- 25982141
TI  - Body Mass Index Accuracy in Preadolescents: Can We Trust Self-Report or Should We
      Seek Parent Report?
AB  - OBJECTIVES: To assess the accuracy of self- and parent-report of weight, height,
      and body mass index (BMI) in children between 8 and 12 years of age and to
      determine whether self- or parent-report should be preferred for preadolescents'
      subjective measures. STUDY DESIGN: Through at-home questionnaires, 875
      preadolescent children (44% boys; 56% girls) and their parents (N = 821) were
      asked to report the children's weight and height. Objective weight and height
      were measured at school by trained interviewers. RESULTS: Correlations between
      objective, self-reported, and parent-reported measures were strong for weight,
      height, and BMI, but children and parents generally underestimated the children's
      weight by about 1 kg, their height by less than 1 cm, and their BMI by less than
      0.25 kg/m(2). The magnitude of the underestimation varied by age, sex, and BMI
      category, with older children, girls, and children in the overweight and obese
      BMI categories underestimating their weight to a greater extent. Weight estimates
      provided by girls' parents tended to be lower than the real values more often
      than those of boys' parents. CONCLUSIONS: Children and parents are likely to
      misreport children's weight, height, and BMI. For most youths aged 8 years of age
      and older, self-report appears as accurate as parent-report and could, therefore,
      be used interchangeably.

PMID- 25982142
TI  - Clinical Presentation and Five-Year Therapeutic Management of Very Early-Onset
      Inflammatory Bowel Disease in a Large North American Cohort.
AB  - OBJECTIVE: To evaluate the presentation, therapeutic management, and long-term
      outcome of children with very early-onset (VEO) (<= 5 years of age) inflammatory
      bowel disease (IBD). STUDY DESIGN: Data were obtained from an inception cohort of
      1928 children with IBD enrolled in a prospective observational registry at
      multiple centers in North America. RESULTS: One hundred twelve children were <= 5
      years of age with no child enrolled at <1 year of age. Of those, 42.9% had
      Crohn's disease (CD), 46.4% ulcerative colitis (UC), and 10.7% had IBD
      unclassified. Among the children with CD, children 1-5 years of age had more
      isolated colonic disease (39.6%) compared with 6- to 10-year-olds (25.3%, P =
      .04), and 11- to 16-year-olds (22.3%, P < .01). The change from a presenting
      colon-only phenotype to ileocolonic began at 6-10 years. Children 1-5 years of
      age with CD had milder disease activity (45.8%) at diagnosis compared with the
      oldest group (28%, P = .01). Five years postdiagnosis, there was no difference in
      disease activity among the 3 groups. However, compared with the oldest group, a
      greater proportion of 1- to 5-year-olds with CD were receiving corticosteroids (P
      < .01) and methotrexate (P < .01), and a greater proportion of 1- to 5-year-olds
      with UC were receiving mesalamine (P < .0001) and thiopurine immunomodulators (P
      < .0002). CONCLUSIONS: Children with VEO-CD are more likely to have mild disease
      at diagnosis and present with a colonic phenotype with change to an ileocolonic
      phenotype noted at 6-10 years of age. Five years after diagnosis, children with
      VEO-CD and VEO-UC are more likely to have been administered corticosteroids and
      immunomodulators despite similar disease activity in all age groups. This may
      suggest development of a more aggressive disease phenotype over time.

PMID- 25982143
TI  - Association of Adiponectin with Adolescent Cardiovascular Health in a Dietary
      Intervention Study.
AB  - OBJECTIVE: To investigate whether an infancy-onset, low saturated fat-oriented
      dietary intervention influences serum adiponectin concentration in adolescents,
      and to study the association of adiponectin with subclinical markers of vascular
      health, and cardio-metabolic risk factors. STUDY DESIGN: The longitudinal,
      randomized Special Turku Coronary Risk Factor Intervention Project aimed to
      modify child's dietary fat quality replacing saturated fat with unsaturated fat.
      Serum adiponectin (n = 521) along with weight, height, high-density lipoprotein
      cholesterol, C-reactive protein (CRP), triglycerides, and insulin were measured
      at age 15 years. Adiposity was assessed using body mass index, waist
      circumference, and abdominal fat thickness measured with ultrasound. Metabolic
      syndrome was defined according to International Diabetes Foundation criteria.
      Vascular ultrasound measures including carotid intima-media thickness (IMT) were
      assessed. RESULTS: Adiponectin concentrations were similar in the intervention
      and control groups (P = .16). Adiponectin associated with carotid IMT (r = -0.13,
      P = .005), high-density lipoprotein cholesterol (r = 0.18, P < .0001),
      triglycerides (r = -0.16, P = .0004), CRP (r = -0.10, P = .02), insulin (r = 
      0.14, P = .002), and adiposity (r = -0.18-0.24, P <= .0001). When adjusted for
      adiposity indices, the association with carotid IMT was only marginally diluted
      (P = .03-.06), but the associations with insulin and CRP became nonsignificant.
      Adolescents with adiponectin <=median had 4-fold risk of metabolic syndrome than
      peers with adiponectin >median (CI 1.8-10.2, P = .0001). CONCLUSIONS: In healthy
      adolescents, low serum adiponectin is related with carotid IMT and metabolic
      syndrome. We found no evidence that repeated low saturated fat-oriented dietary
      counseling would influence serum adiponectin in adolescence. TRIAL REGISTRATION:
      Registered with ClinicalTrials.gov: NCT00223600.

PMID- 25982144
TI  - 5-Aminolevulinic acid-mediated sonodynamic therapy induces anti-tumor effects in
      malignant melanoma via p53-miR-34a-Sirt1 axis.
AB  - BACKGROUD: Malignant melanoma is a very refractory skin tumor due to its high
      metastasis, poor prognosis, and insensitivity to chemotherapy. Sonodynamic
      therapy has recently evolved as a potential method to treat cancers. In this
      study, 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) was used to
      treat malignant melanoma in vivo. OBJECTIVE: To investigate whether ALA-SDT
      induces anti-tumor effects in malignant melanoma and to see if miRNAs are
      involved in this process. METHODS: Tumor transplantation experiments in BALB/c
      nude mice were used to assess anti-tumor effects after ALA-SDT treatment. Cell
      apoptosis was evaluated by TUNEL assays and cell proliferation was measured using
      immunohistochemisty with anti-PCNA antibody. Microarray analysis was performed to
      measure miRNAs expressions. Endogenous miR-34a and its upstream and downstream
      genes were assayed by real-time PCR. Western blottings were used to determine
      these protein expressions. Intracellular ROS levels were detected by measuring
      the fluorescence intensity of DCF. RESULTS: Tumor transplantation experiments
      revealed that ALA-SDT could inhibit mouse melanoma cell proliferation and tumor
      growth. Compared with the control group, TUNEL assays revealed that apoptosis was
      increased and proliferation was inhibited in the SDT group. Real-time PCR
      analysis showed 14-fold increase of miR-34a expression in the SDT group compared
      to the control group. In addition, ALA-SDT significantly increased intracellular
      ROS levels in vitro, which were almost inhibited by the ROS scavenger NAC. Also,
      the mRNA, total protein, and acetylation levels of p53 were increased, whereas
      some downstream anti-apoptotic or pro-proliferative factors of miR-34a such as
      BCL2, CCND1, CDK6, and SIRT1 were decreased in the SDT group compared with the
      control, ALA alone, and ultrasound alone groups. When miR-34a was inhibited in
      vitro, the protein expressions of BCL2, CCND1, CDK6, and SIRT1 recovered. By
      targeting SIRT1, which inhibits p53 acetylation, miR-34a promoted the
      transcriptional activity of p53, and finally led to increased expression of miR
      34a itself. Therefore, the p53, miR-34a, and SIRT1 constituted a positive
      feedback loop. CONCLUSION: ALA-SDT showed synergistic anti-tumor effects in
      malignant melanoma by constituting a positive feedback loop of p53-miR-34a-Sirt1
      axis.

PMID- 25982145
TI  - Mutation analyses of patients with dyschromatosis symmetrica hereditaria: Ten
      novel mutations of the ADAR1 gene.

PMID- 25982146
TI  - Update on autosomal recessive congenital ichthyosis: mRNA analysis using hair
      samples is a powerful tool for genetic diagnosis.
AB  - Research on the molecular genetics and pathomechanisms of autosomal recessive
      congenital ichthyosis (ARCI) has advanced considerably and several causative
      genes and molecules underlying the disease have been identified. Three major ARCI
      phenotypes are harlequin ichthyosis (HI), lamellar ichthyosis (LI), and
      congenital ichthyosiform erythroderma (CIE). Skin barrier defects are involved in
      the pathogenesis of ARCI. In this review, the causative genes of ARCI and its
      phenotypes as well as recent advances in the field are summarized. The known
      causative molecules underlying ARCI include ABCA12, TGM1, ALOXE3, ALOX12B,
      NIPAL4, CYP4F22, PNPLA1, CERS3, and LIPN. It is important to examine genetic
      associations and to elucidate the pathomechanisms of ARCI to establish effective
      therapies and beneficial genetic counseling. Next-generation sequencing is a
      promising method that enables the detection of causative disease mutations, even
      in cases of unexpected concomitant genetic diseases. For genetic diagnosis,
      obtaining mRNA from hair follicle epithelial cells, which are analogous to
      keratinocytes in the interfollicular epidermis, is convenient and minimally
      invasive in patients with ARCI. We confirmed that our mRNA analysis method using
      hair follicle samples can be applied not only to keratinization disorders, but
      also to other genetic diseases in the dermatology field. Studies that suggest
      potential next-generation therapies using ARCI model mice are also reviewed. 

PMID- 25982147
TI  - Notch down-regulation in regenerated epidermis contributes to enhanced expression
      of interleukin-36alpha and suppression of keratinocyte differentiation during
      wound healing.
AB  - BACKGROUND: Notch signaling controls a number of cellular processes, including
      cell fate decisions, proliferation, differentiation, and survival/apoptosis, in
      multiple tissues. In the epidermis, Notch1 functions as a molecular switch that
      controls the transition of cells from an undifferentiated state into a
      differentiated state. OBJECTIVE: To clarify the functions of Notch in the
      regenerated epidermis during wound healing. METHODS: Wounds on mouse skin were
      immunostained. To investigate the functions of Notch, Notch was inhibited in
      primary keratinocytes by treatment with a gamma-secretase inhibitor and by small
      interfering RNA-mediated knockdown, and was activated by a recombinant adenovirus
      approach. RESULTS: Notch1 and Notch2 were down-regulated in the regenerated
      epidermis during wound healing. To clarify the significance of this down
      regulation, we examined its effect on expression of the interleukin (IL)-1 family
      of proinflammatory cytokines because wounds are exposed to pathogens from the
      outside world. Among the IL-1 family, IL-36alpha expression was induced by Notch
      inhibition. This was consistent with the decreased IL-36alpha expression in Notch
      overexpressing keratinocytes. Notch down-regulation in the regenerated epidermis
      may reinforce defense against stress from the outside world by inducing IL
      36alpha expression. Next, we examined the effects of Notch down-regulation on
      keratinocyte growth and differentiation. Notch down-regulation did not alter
      keratinocyte proliferation. On the other hand, Notch1 down-regulation suppressed
      induction of spinous layer-specific keratins (keratin1 and keratin10) in
      keratinocytes, which was consistent with the decreased expression of these
      keratins in the regenerated epidermis. The reduced levels of these keratins would
      increase cellular flexibility. CONCLUSION: Notch down-regulation in the epidermis
      appears to contribute to tissue regeneration during wound healing.

PMID- 25982148
TI  - Semantic Search in the Remote Associates Test.
AB  - Searching through semantic memory may involve the use of several retrieval cues.
      In a verbal fluency task, the set of available cues is limited and every
      candidate word is a target. Individuals exhibit clustering behavior as predicted
      by optimal foraging theory. In another semantic search task, the remote
      associates task (RAT), three cues are presented and a single target word has to
      be found. Whereas the task has been widely studied as a task of creativity or
      insight problem solving, in this article, the RAT is treated as a semantic
      retrieval task and assessed from the perspective of information foraging theory.
      Experiments are presented that address the superadditive combination of cues and
      the anti-clustering behavior in the recall sequence. A new type of search
      behavior in the RAT is put forward that involves maximizing the difference in
      activation between target and distractors. This type of search is advantageous
      when the target is weak and cue patches are contaminated with strong competitors.

PMID- 25982150
TI  - Impact of pre-treatment with somatostatin analogs on surgical management of
      acromegalic patients referred to a single center.
AB  - First-line treatment of patients with growth hormone secreting adenomas is
      surgical resection. Disease control can be obtained by surgery (one or multiple
      steps), in case followed by medical treatment or adjuvant radiation therapy
      (radiosurgery or radiotherapy). The impact of pre-surgical treatment with
      somatostatin analogs (SSAs) on surgical outcome is still controversial. The aim
      of this study is to retrospectively evaluate the impact of SSA pre-treatment on
      biochemical outcome and post-surgical hypopituitarism in a consecutive surgical
      series from a single referral centre, with data covering 17 years' experience and
      to investigate the possible predictive value of early postoperative insulin-like
      factor 1 (IGF-I) on long-term biochemical control. Data from 68 acromegalic
      patients were revised. Endocrinological long-term follow-up (minimum 6 months)
      was available for 57 patients. Eighty-eight percent of patients received a single
      step surgical treatment (single surgery, with or without adjuvant medical
      therapy). The remaining 12% underwent a multi-step strategy: redo-surgery (three
      macroadenomas) and/or radiation (four macro- and two microadenomas). Pre-surgical
      SSA treatment was performed in 77.9% and resulted in a significant lowering of
      basal IGF-I values (p = 0.0001). Early post-surgical IGF-I was significantly
      lower in patients biochemically controlled with single surgery alone (p = 0.016)
      and after overall treatment strategies (p = 0.005). Normalization of GH and IGF-I
      was obtained in 56.1%, and normalization of either one of them in 27.8% of
      patients. No major surgery-related complications occurred. Post-treatment
      hypopituitarism occurred in 11.9% and was lower in SSA pre-treated patients. Our
      results well compare with other recently published series. Very early post
      surgical IGF-I improvement might be a useful predictor for biochemical disease
      control. Moreover, our results suggest that pre-surgical treatment with
      somatostatin analogs seems to prevent hypopituitarism.

PMID- 25982151
TI  - Low risk of coronary artery disease in patients with acromegaly.
AB  - The aims of this study are to determine the prevalence of coronary
      atherosclerosis in acromegalic patients and to investigate the relationship
      between the coronary artery calcium score (CS) and acromegaly status and clinical
      parameters [Framingham risk score (FRS)]. Fifty-six acromegalic patients and
      paired non-acromegalic volunteers were stratified according to the FRS into low-,
      intermediate-, and high-risk groups. CS was assessed using multidetector computed
      tomography. The patients were considered to have controlled or active acromegaly
      at the time they were submitted to evaluation. Sixty-six percent of acromegalic
      patients exhibited arterial hypertension, 36 % had diabetes mellitus, and 34 %
      had hypercholesterolemia. The median FRS and the median risk for cardiovascular
      event within the next 10 years were similar in the acromegalics and the controls.
      The median total CS and CS >75th percentile didn't differ significantly between
      these groups. In patients with controlled acromegaly, a low, intermediate, or
      high FRS risk was observed in 86, 14, and 0 %, respectively. In patients with
      active disease, a low, intermediate, or high FRS risk was verified in 94, 3, and
      3 %, respectively, and differences between the controlled and active groups were
      not significant. Seventy-two percent of the patients had total CS = 0, and there
      were no differences between the controlled and active groups. The risk of
      coronary artery disease in acromegalic patients, determined according to FRS and
      CS, is low despite the high prevalence of metabolic abnormalities.

PMID- 25982152
TI  - Correlates of fractures in elderly, diabetic outpatients.
AB  - It is widely recognized that patients presenting diabetes are at increased risk
      for fractures. In a retrospective case-control study, 101 cases were selected
      from medical charts of outpatients older than 70 with diabetes mellitus and a
      fracture within the past 5 years. Glycosylated hemoglobin (HbA1c) had been
      measured within 4 months around the assessment. Each case was matched for sex and
      age with one control, diabetic patient with no fracture. HbA1c level was similar
      in both groups. Patients with fractures presented significantly lower BMIs than
      controls, and had a higher rate of declared osteoporosis and comorbidity. A small
      number of cases were using vitamin D supplements while more were treated with
      benzodiazepine, opiates and Selective serotonin reuptake inhibitors (SSRI). This
      study suggests that, rather than the tight control of blood glucose, other
      factors such as medication and comorbidity could be associated with fracture risk
      in elderly diabetics. 

PMID- 25982154
TI  - The evolution of prolonged life after reproduction.
AB  - Why females of some species cease ovulation before the end of their natural
      lifespan is a longstanding evolutionary puzzle. For many species in captivity,
      post-reproductive life is simply an epiphenomenon of lengthened lifespan. Yet in
      natural populations of humans as well as some cetaceans and insects, reproductive
      senescence occurs much faster than somatic aging and females exhibit prolonged
      post-reproductive lifespans (PRLSs). Determining the mechanisms and functions
      that underpin PRLSs has proved a significant challenge. Here we bring together
      both classic and modern hypotheses proposed to explain PRLSs and discuss their
      application to both human and nonhuman animals. By taking an integrative and
      broad taxonomic approach we highlight the need to consider multiple interacting
      explanations for the evolution of PRLSs. 

PMID- 25982153
TI  - Hybrid zones: windows on climate change.
AB  - Defining the impacts of anthropogenic climate change on biodiversity and species
      distributions is currently a high priority. Niche models focus primarily on
      predicted changes in abiotic factors; however, species interactions and adaptive
      evolution will impact the ability of species to persist in the face of changing
      climate. Our review focuses on the use of hybrid zones to monitor responses of
      species to contemporary climate change. Monitoring hybrid zones provides insight
      into how range boundaries shift in response to climate change by illuminating the
      combined effects of species interactions and physiological sensitivity. At the
      same time, the semipermeable nature of species boundaries allows us to document
      adaptive introgression of alleles associated with response to climate change. 

PMID- 25982155
TI  - Have We Given Up on Breast Cancer Metastasis? Global Trends in Breast Cancer
      Metastasis Research Productivity.

PMID- 25982156
TI  - Assessing the Quality of Death and Dying in an Integrated Health Care System in
      Rural Pennsylvania.
AB  - CONTEXT: With growing emphasis on improving the value of health care, there is
      increased scrutiny of quality outcomes and high health expenditures during the
      final months of life. OBJECTIVES: The purpose of this project is to answer 1) how
      do next of kin (NOK) perceive the quality of their loved ones' dying and death;
      2) are there patient and NOK characteristics that predict lower quality; and 3)
      are there structural aspects of care associated with lower quality? METHODS: A
      mailed survey was administered to a stratified random sample of NOK of Geisinger
      Health System patients who had died in the past year. The Quality of Death and
      Dying, the General Anxiety Disorder seven-item scale, the Patient Health
      Questionnaire eight-item depression scale, and selected questions from the
      Toolkit of Instruments to Measure End of Life Care were used. RESULTS: There were
      672 respondents. Significant predictors of Quality of Death and Dying score were
      number of doctors involved in care (P = 0.0415), location of death (P < 0.0001),
      frequency of receiving confusing or contradictory information (P < 0.0001),
      illness progression (P = 0.0343), Patient Health Questionnaire-2 score (P =
      0.0148), and General Anxiety Disorder seven-item scale score (P < 0.0070).
      CONCLUSION: Several findings suggest that factors such as NOK depression and
      anxiety, prolonged illness, dying in the hospital, receipt of conflicting
      information, and confusion around the doctor in charge are associated with lower
      quality of the dying and death experience for NOK. Further investigation is
      warranted to facilitate high-quality measurement and the use of measurement
      results to improve care.

PMID- 25982157
TI  - The eye as a window to a rare disease: ectopia lentis and homocystinuria, a
      Pakistani perspective.
AB  - Non-traumatic ectopia lentis has been associated with genetic diseases in a
      European population; however, no data are present in regards to this in a
      Pakistani demographic. In third world countries such as Pakistan, due to the lack
      of screening tests, this disease has the potential to remain undiagnosed till a
      later age, at which point the eye through the finding of ectopia lentis has
      potential to lead to the right diagnosis. Our purpose was to investigate
      Pakistani patients presenting with ectopia lentis who have underlying
      homocystinuria and establish a relationship between the two. Additionally, we
      elicited various systemic and ophthalmic features in these settings. Ten
      Pakistani patients presenting with decreased vision and ectopia lentis with
      concomitant homocystinuria were included in the study. Assessment of systemic and
      ophthalmic features was performed. All patients presented with visual
      deterioration. All 20 (100 %) eyes had ectopia lentis, of which, 15 (75 %) eyes
      had inferior subluxation, whereas five (25 %) eyes had anterior subluxation of
      the crystalline lens. Ectopia lentis and homocystinuria appear to have a strong
      correlation in Pakistani population. Ectopia lentis has the potential to serve as
      an important clue to its diagnosis, which may in turn lead to decreased morbidity
      if diagnosed in a timely fashion.

PMID- 25982158
TI  - Predictability of Sirius dual-scanning corneal tomography in the measurement of
      corneal power after photorefractive surgery.
AB  - Determining an accurate central corneal power (K) measurement is crucial for
      calculating the intraocular lens power in patients who are undergoing cataract
      extraction. The ideal method for measuring K is to use a device that works
      independently of the refractive surgery information. The Scheimpflug camera
      system offers a promising means of measuring the true corneal power after
      keratorefractive surgery. In this study, we investigated the accuracy of this
      system in measuring central corneal power after photorefractive corneal surgery
      by comparing it to the theoretically derived central corneal power by history
      method. A total of 120 eyes of 65 (35 females and 30 males) patients were
      included in this study. The mean change of refraction at the spectacle plane was
      3.75 D, whereas the mean change of refraction at the corneal plane was 3.37 D.
      Using the Sirius dual-scanning corneal tomography, the mean change in corneal
      power was 3.96 D. No significant differences were detected between the mean post
      operative corneal power measured by the Sirius tomographer and the mean change in
      refraction at the corneal plane calculated clinically (P = 0.076) and the
      correlation was found to be high (0.913). This study suggests that Sirius dual
      scanning corneal tomography offers high predictability when measuring the central
      5 mm corneal power in patients who have had myopic corneal photorefractive
      surgery.

PMID- 25982159
TI  - Grip strength and mortality: a biomarker of ageing?

PMID- 25982161
TI  - Maternal Medicine. Preface: Issue 29.5.

PMID- 25982162
TI  - Self- and rater-assessed effectiveness of "thinking-aloud" and "regular" morning
      report to intensify young physicians' clinical skills.
AB  - BACKGROUND: This study compared the effects of the "thinking aloud" (TA) morning
      report (MR), which is characterized by sequential and interactive case discussion
      by all participants, with "regular" MR for clinical skill training of young
      physicians. METHODS: Between February 2011 and February 2014, young physicians
      [including postgraduate year-1 (PGY1) residents, interns, and clerks) from our
      hospital were sequentially enrolled and followed for 3 months. The self- and
      rater-assessed educational values of two MR models for building up clinical
      skills of young physicians were compared. RESULTS: The junior (intern and clerk)
      attendees had higher self-assessed educational values scores and reported post
      training application frequency of skills trained by TA MR compared with the
      senior (PGY1 resident) attendees. Higher average and percentage of increased
      overall rater-assessed OSCE scores were noted among the regular MR senior
      attendees and TA MR junior attendees than in their corresponding control groups
      (regular MR junior attendees and TA MR senior attendees). Interestingly, regular
      MRs provided additional beneficial effects for establishing the "professionalism,
      consulting skills and organization efficiency" aspects of clinical skills of
      senior/junior attendees. Moreover, senior and junior attendees benefited the most
      by participating in seven sessions of regular MR and TA MR each month,
      respectively. CONCLUSION: TA MR effectively trains junior attendees in basic
      clinical skills, whereas regular MR enhances senior attendees' "work reports,
      professionalism, organizational efficiency, skills in dealing with controversial
      and professional issues." Undoubtedly, all elements of the two MR models should
      be integrated together to ensure patient safety and good discipline among young
      physicians.

PMID- 25982163
TI  - Appendectomy timing: Will delayed surgery increase the complications?
AB  - BACKGROUND: This study investigated whether the time from emergency room
      registration to appendectomy (ETA) would affect the incidence of perforation and
      postoperative complications in patients with acute appendicitis. METHODS:
      Patients who underwent an appendectomy at the Ren-Ai branch of Taipei City
      Hospital between January 2010 and October 2012 were retrospectively reviewed.
      Their demographics, white blood cell count, C-reactive protein, body temperature,
      computed tomography scan usage, operation method, pathology report, postoperative
      complication, length of hospital stay, and ETA were abstracted. Multivariate
      analysis was performed to search the predictors, including ETA, of outcomes for
      the perforation and postoperative complication rates. RESULTS: A total of 236
      patients were included in the study. Perforation occurred in 12.7% (30/236) and
      postoperative complications developed in 24.1% (57/236) of these patients. There
      were 121 patients with ETA <8 hours, 88 patients with ETA of 8-24 hours, and 27
      patients with ETA >24 hours; patients with ETA >24 hours had significantly longer
      hospital stay. Univariate analysis showed that perforated patients were
      significantly older, and had higher C-reactive protein level, longer hospital
      stay, and higher complication rate. Patients who developed postoperative
      complications were significantly older, and had higher neutrophil count, less use
      of computed tomography, and higher open appendectomy rate. After multivariate
      analysis, age >=55 years was the only predictor for perforation [odds ratio (OR)
      = 3.65; 95% confidence interval (CI), 1.54-8.68]; for postoperative
      complications, age >=55 years (OR = 1.65; 95% CI, 1.84-3.25), perforated
      appendicitis (OR = 3.17; 95% CI, 1.28-7.85), and open appendectomy (OR = 3.21;
      95% CI, 1.36-7.58) were associated. ETA was not a significant predictor in both
      analyses. CONCLUSION: In our study, it was observed that although longer ETA was
      associated with longer hospitalization, ETA was not correlated with postoperative
      complications. Our results inclined toward the position that appendectomy can be
      performed as a semielective surgery.

PMID- 25982164
TI  - Cerebrospinal fluid protein dynamic driver network: At the crossroads of brain
      tumorigenesis.
AB  - To get a better understanding of the ongoing in situ environmental changes
      preceding the brain tumorigenesis, we assessed cerebrospinal fluid (CSF) proteome
      profile changes in a glioma rat model in which brain tumor invariably developed
      after a single in utero exposure to the neurocarcinogen ethylnitrosourea (ENU).
      Computationally, the CSF proteome profile dynamics during the tumorigenesis can
      be modeled as non-smooth or even abrupt state changes. Such brain tumor
      environment transition analysis, correlating the CSF composition changes with the
      development of early cellular hyperplasia, can reveal the pathogenesis process at
      network level during a time before the image detection of the tumors. In our
      controlled rat model study, matched ENU- and saline-exposed rats' CSF proteomics
      changes were quantified at approximately 30, 60, 90, 120, 150 days of age (P30,
      P60, P90, P120, P150). We applied our transition-based network entropy (TNE)
      method to compute the CSF proteome changes in the ENU rat model and test the
      hypothesis of the critical transition state prior to impending hyperplasia. Our
      analysis identified a dynamic driver network (DDN) of CSF proteins related with
      the emerging tumorigenesis progressing from the non-hyperplasia state. The DDN
      associated leading network CSF proteins can allow the early detection of such
      dynamics before the catastrophic shift to the clear clinical landmarks in
      gliomas. Future characterization of the critical transition state (P60) during
      the brain tumor progression may reveal the underlying pathophysiology to device
      novel therapeutics preventing tumor formation. More detailed method and
      information are accessible through our website at
      http://translationalmedicine.stanford.edu.

PMID- 25982165
TI  - Mesenchymal stromal cells and the innate immune response.
AB  - Mesenchymal stromal cells (MSC) have been exploited for their immunomodulatory
      properties in the treatment of a number of immune-based disorders, including
      Graft versus Host Disease (GvHD) and type 1 diabetes. The mechanisms for inducing
      therapeutic effect still remain largely unknown however, with research focused on
      understanding how MSCs interact with individual immune cell subsets. Within this
      review we address what is known about the interactions of MSCs with cells of the
      innate immune system, how they respond to their microenvironment and how this
      relates to therapeutic effects we see both within in vivo animal models and in
      clinical trials. 

PMID- 25982166
TI  - The diverse origins of the human gene pool.
AB  - Analyses of the genomes of Neanderthals and Denisovans, the closest evolutionary
      relatives of present-day humans, suggest that our ancestors were part of a web of
      now-extinct populations linked by limited, but intermittent or sometimes perhaps
      even persistent, gene flow. 

PMID- 25982167
TI  - Non-coding RNA: X chromosome inactivation unravelled.

PMID- 25982168
TI  - Disease genetics: Network effects of disease mutations.

PMID- 25982170
TI  - Ageing: Heterochromatin disorganization associated with premature ageing.

PMID- 25982160
TI  - Prognostic value of grip strength: findings from the Prospective Urban Rural
      Epidemiology (PURE) study.
AB  - BACKGROUND: Reduced muscular strength, as measured by grip strength, has been
      associated with an increased risk of all-cause and cardiovascular mortality. Grip
      strength is appealing as a simple, quick, and inexpensive means of stratifying an
      individual's risk of cardiovascular death. However, the prognostic value of grip
      strength with respect to the number and range of populations and confounders is
      unknown. The aim of this study was to assess the independent prognostic
      importance of grip strength measurement in socioculturally and economically
      diverse countries. METHODS: The Prospective Urban-Rural Epidemiology (PURE) study
      is a large, longitudinal population study done in 17 countries of varying incomes
      and sociocultural settings. We enrolled an unbiased sample of households, which
      were eligible if at least one household member was aged 35-70 years and if
      household members intended to stay at that address for another 4 years.
      Participants were assessed for grip strength, measured using a Jamar dynamometer.
      During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause
      mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial
      infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia
      or chronic obstructive pulmonary disease (COPD), hospital admission for any
      respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury
      due to fall, and fracture. Study outcomes were adjudicated using source documents
      by a local investigator, and a subset were adjudicated centrally. FINDINGS:
      Between January, 2003, and December, 2009, a total of 142,861 participants were
      enrolled in the PURE study, of whom 139,691 with known vital status were included
      in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%)
      of 139,691 participants died. After adjustment, the association between grip
      strength and each outcome, with the exceptions of cancer and hospital admission
      due to respiratory illness, was similar across country-income strata. Grip
      strength was inversely associated with all-cause mortality (hazard ratio per 5 kg
      reduction in grip strength 1.16, 95% CI 1.13-1.20; p<0.0001), cardiovascular
      mortality (1.17, 1.11-1.24; p<0.0001), non-cardiovascular mortality (1.17, 1.12
      1.21; p<0.0001), myocardial infarction (1.07, 1.02-1.11; p=0.002), and stroke
      (1.09, 1.05-1.15; p<0.0001). Grip strength was a stronger predictor of all-cause
      and cardiovascular mortality than systolic blood pressure. We found no
      significant association between grip strength and incident diabetes, risk of
      hospital admission for pneumonia or COPD, injury from fall, or fracture. In high
      income countries, the risk of cancer and grip strength were positively associated
      (0.916, 0.880-0.953; p<0.0001), but this association was not found in middle
      income and low-income countries. INTERPRETATION: This study suggests that
      measurement of grip strength is a simple, inexpensive risk-stratifying method for
      all-cause death, cardiovascular death, and cardiovascular disease. Further
      research is needed to identify determinants of muscular strength and to test
      whether improvement in strength reduces mortality and cardiovascular disease.
      FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

PMID- 25982171
TI  - Ethnicity and risk of lower limb amputation in people with Type 2 diabetes: a
      prospective cohort study.
AB  - AIM: Lower limb amputation is a serious complication of diabetic foot disease and
      there are unexplained ethnic variations in incidence. This study investigates the
      risk of amputation among different ethnic groups after adjusting for demographic,
      socio-economic status and clinical variables. METHODS: We used primary care data
      from a large national multi-ethnic cohort of patients with Type 2 diabetes in New
      Zealand and linked hospital records. The primary outcome was time from initial
      data collection to first lower limb amputation. Demographic variables included
      age of onset and duration since diabetes diagnosis, gender, ethnicity and socio
      economic status. Clinical variables included smoking status, height and weight,
      blood pressure, HbA1c , total cholesterol/HDL ratio and albuminuria. Cox
      proportional hazards models were used. RESULTS: There were 892 lower limb
      amputations recorded among 62 002 patients (2.11 amputations per 1000 person
      years), followed for a median of 7.14 years (422 357 person-years). After
      adjusting for demographic and socio-economic variables and compared with
      Europeans, Maori had the highest risk [hazard ratio (HR) 1.84 (95%CI:1.54-2.19)],
      whereas East Asians [HR 0.18, (0.08-0.44)] and South Asians [HR 0.39 (0.22-0.67)]
      had the lowest risk. Adjusting for available clinical variables reduced the
      differences but they remained substantial [HR 1.61 (1.35-1.93), 0.23 (0.10-0.56)
      and 0.48 (0.27-0.83), respectively]. CONCLUSIONS: Ethnic groups had significantly
      different risk of lower limb amputation, even after adjusting for demographic and
      some major clinical risk factors. Barriers to care should be addressed and
      intensive prevention strategies known to reduce the incidence of lower limb
      amputations could be prioritized to those at greatest risk.

PMID- 25982172
TI  - Identification of glucose-6-phosphate transporter as a key regulator functioning
      at the autophagy initiation step.
AB  - Autophagy is a catabolic process involving autophagosome formation via lysosome.
      However, the initiation step of autophagy is largely unknown. We found an
      interaction between ULK1 and ATG9 in mammalian cells and utilized the interaction
      to identify novel regulators of autophagy upstream of ULK1. We established a cell
      based screening assay employing bimolecular fluorescence complementation. By
      performing gain-of-function screening, we identified G6PT as an autophagy
      activator. G6PT enhanced the interaction between N-terminal Venus-tagged ULK1 and
      C-terminal Venus-tagged ATG9, and increased autophagic flux independent of its
      transport activity. G6PT negatively regulated mTORC1 activity, demonstrating that
      G6PT functions upstream of mTORC1 in stimulating autophagy. 

PMID- 25982174
TI  - Idiopathic calcified apical aneurysm of the left ventricle in an asymptomatic
      adult.

PMID- 25982173
TI  - Depression and sexual risk behaviours among people who inject drugs: a gender
      based analysis.
AB  - Background Although many people who inject drugs (PID) contend with
      comorbidities, including high rates of mental illness, limited attention has been
      given to the differences in comorbidities among men and women or the potential
      links between psychiatric disorders and HIV risk behaviours. We sought to
      longitudinally examine associations between depression and HIV-related sexual
      risk behaviours among PID, stratified by gender. METHODS: Data were derived from
      a prospective cohort of PID in Vancouver, Canada between December 2005 and
      November 2009. Using generalised estimating equations, we examined the
      relationship between depressive symptoms and two types of sexual HIV risk
      behaviours: engaging in unprotected sex; and having multiple sexual partners. All
      analyses were stratified by self-reported gender. RESULTS: Overall, 1017 PID
      participated in this study, including 331 (32.5%) women. At baseline, women
      reported significantly higher depressive symptoms than men (P<0.001). In
      multivariate generalised estimating equations analyses, after adjustment for
      potential social, demographic and behavioural confounders, more severe depressive
      symptomology remained independently associated with engaging in unprotected sex
      [adjusted odds ratio (AOR)=1.62, 95% confidence interval (CI): 1.18-2.23] and
      having multiple sexual partners (AOR=1.54, 95% CI: 1.09-2.19) among women, but
      was only marginally associated with having multiple sexual partners among men
      (AOR=1.18, 95% CI: 0.98-1.41). CONCLUSIONS: These findings call for improved
      integration of psychiatric screening and treatment services within existing
      public health initiatives designed for PID, particularly for women. Efforts are
      also needed to address sexual risk-taking among female PID contending with
      clinically significant depression.

PMID- 25982175
TI  - Predicting successful percutaneous coronary intervention in patients with chronic
      total occlusion: the incremental value of a novel morphological parameter
      assessed by computed tomography.
AB  - To study the relationship between percutaneous coronary intervention (PCI)
      success and various morphological index evaluated by coronary computed tomography
      angiography (CCTA) in patients with coronary chronic total occlusion (CTO). 272
      Consecutive patients with 281 CTO lesions diagnosed by CCTA and invasive coronary
      angiography were prospectively enrolled. The luminal attenuation of proximal
      segment of CTO lesions was measured. Other parameters, like lesion length,
      coronary calcium score, torturous course, stump morphology were also recorded.
      The attenuation of the proximal segment of CTO lesions was significantly higher
      in PCI failure group than it was in PCI success group (88 +/- 19.7 vs. 70.2 +/-
      13, p < 0.001). Lesion length in PCI failure group was longer than those in PCI
      success group (20.4 +/- 11.2 vs. 15.1 +/- 5.85 mm, p < 0.001) and lesions in PCI
      failure group were more heavily calcified than lesions in PCI success group
      (Agatston score 61 vs. 5.7, p < 0.001). The attenuation of the proximal segment
      of CTO lesions, along with occlusion length and total coronary calcium score were
      significant independent predictors of PCI failure. The attenuation of the
      proximal segment of CTO lesions, along with occlusion length and total coronary
      calcium score as assessed by CCTA have predictive value for PCI outcomes.

PMID- 25982176
TI  - Evaluation of right and left heart mechanics in patients with chronic
      thromboembolic pulmonary hypertension before and after pulmonary
      thromboendarterectomy.
AB  - The aim of the present study was to evaluate of the right and left heart
      mechanics by two-dimensional (2D) speckle tracking echocardiography (STE) in
      chronic thromboembolic pulmonary hypertension (CTEPH) patients before and after
      pulmonary thromboendarterectomy (PTE). A total of 40 consecutive CTEPH patients
      (mean age 49.3 +/- 13.5 years, 27 female) were included. 2D STE was performed in
      all patients before, and 3 months, after PTE. 12 months of prognostic data were
      also recorded via the use of telephone calls. Postoperative 6-minute walk test
      (6MWT) distances were significantly longer than preoperative values (410.5 +/-
      61.5 vs. 216.6 +/- 131.4 m, p < 0.001). Postoperative left ventricular (LV) and
      right ventricular (RV) systolic functions (LV EF, TAPSE, RVS) were similar
      compared to preoperative values. While postoperative RV, right atrial (RA) and
      systolic pulmonary artery pressure measurements were significantly lower, LV and
      left atrial (LA) measurements were higher than preoperative values. Postoperative
      LV and RV global longitudinal strain (GLS) measurements were significantly higher
      than preoperative values. Postoperative LV global radial and circumferential
      strain measurements were similar to preoperative values. While postoperative RA
      reservoir and conduit functions were significantly higher, postoperative LA
      reservoir and conduit functions were similar to preoperative values. Correlation
      analysis revealed that baseline 6MWT distances were correlated with LV GLS, RV
      GLS, and RA reservoir and conduit functions in the preoperative and postoperative
      periods. 2D STE indices may help the clinician in assessing the effect of PTE on
      cardiac functions and may also be used for follow-up data in CTEPH patients.

PMID- 25982177
TI  - Multisite clickable modification of proteins using lipoic acid ligase.
AB  - Approaches that allow bioorthogonal and, in turn, site-specific chemical
      modification of proteins present considerable opportunities for modulating
      protein activity and stability. However, the development of such approaches that
      enable site-selective modification of proteins at multiple positions, including
      internal sites within a protein, has remained elusive. To overcome this void, we
      have developed an enzymatic approach for multisite clickable modification based
      on the incorporation of azide moieties in proteins using lipoic acid ligase
      (LplA). The ligation of azide moieties to the model protein, green fluorescent
      protein (GFP), at the N-terminus and two internal sites using lipoic acid ligase
      was shown to proceed efficiently with near-complete conversion. Modification of
      the ligated azide groups with poly(ethylene glycol) (PEG), alpha-d
      mannopyranoside, and palmitic acid resulted in highly homogeneous populations of
      protein-polymer, protein-sugar, and protein-fatty acid conjugates. The
      homogeneity of the conjugates was confirmed by mass spectrometry (MALDI-TOF) and
      SDS-PAGE electrophoresis. In the case of PEG attachment, which involved the use
      of strain-promoted azide-alkyne click chemistry, the conjugation reaction
      resulted in highly homogeneous PEG-GFP conjugates in less than 30 min. As further
      demonstration of the utility of this approach, ligated GFP was also covalently
      immobilized on alkyne-terminated self-assembled monolayers. These results
      underscore the potential of this approach for, among other applications, site
      specific multipoint protein PEGylation, glycosylation, fatty acid modification,
      and protein immobilization. 

PMID- 25982178
TI  - Hypoxia regulates proliferation of acute myeloid leukemia and sensitivity against
      chemotherapy.
AB  - Reduced oxygen partial pressure (pO2, hypoxia) is an important component of the
      bone marrow microenvironment and the hematopoietic stem cell niche. It is unclear
      whether this applies to the leukemic stem cell as well and if differences in pO2
      between the normal hematopoetic and the leukemic stem cell niche exits. Here, we
      demonstrate that while there is no detectable difference in the hypoxic level of
      bone marrow infiltrated by acute myeloid leukemia (AML) and healthy bone marrow,
      physiological hypoxia of 1% O2 itself leads to cell cycle arrest of AML blasts
      (both cell lines and primary AML samples) in the G0/G1 phase with upregulation of
      p27 and consecutive decrease of cells in the S phase. Hence, susceptibility of
      AML blasts toward cytarabine as S phase dependent drug is significantly decreased
      as shown by decreased cytotoxicity in vitro. In addition, cells exposed to
      hypoxia activate PI3K/Akt and increase expression of anti-apoptotic XIAP.
      Inhibition of PI3K can restore cytarabine sensitivity of AML blasts at hypoxic
      conditions. In conclusion, hypoxia mediated effects encountered in the bone
      marrow might contribute to chemoresistance of AML blasts. 

PMID- 25982179
TI  - Perturbation of cellular oxidative state induced by dichloroacetate and arsenic
      trioxide for treatment of acute myeloid leukemia.
AB  - The incidence of acute myeloid leukemia (AML) is rising and the outcome of
      current therapy, which has not changed significantly in the last 40 years, is
      suboptimal. Cellular oxidative state is a credible target to selectively
      eradicate AML cells, because it is a fundamental property of each cell that is
      sufficiently different between leukemic and normal cells, yet its aberrancy
      shared among different AML cells. To this end, we tested whether a short-time
      treatment of AML cells, including cells with FLT3-ITD mutation, with sub-lethal
      dose of dichloroacetate (DCA) (priming) followed by pharmacologic dose of arsenic
      trioxide (ATO) in presence of low-dose DCA could produce insurmountable level of
      oxidative damage that kill AML cells. Using cellular cytotoxicity, apoptotic and
      metabolic assays with both established AML cell lines and primary AML cells, we
      found that priming with DCA significantly potentiated the cytotoxicity of ATO in
      AML cells in a synergistic manner. The combination decreased the mitochondrial
      membrane potential as well as expression of Mcl-1 and GPx in primary AML cells
      more than either drug alone. One patient with AML whose disease was refractory to
      several lines of prior treatments was treated with this combination, and
      tolerated it well. These data suggest that targeting cellular redox balance in
      leukemia may provide a therapeutic option for AML patients with
      relapsed/refractory disease. 

PMID- 25982180
TI  - Serum vitamin D level is associated with disease severity and response to
      ursodeoxycholic acid in primary biliary cirrhosis.
AB  - BACKGROUND: Serum vitamin D levels are associated with bone complications in
      patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a
      nonskeletal role of vitamin D in various autoimmune and liver diseases. AIM: To
      investigate the clinical relevance of vitamin D levels in PBC, especially their
      association with the therapeutic effects of ursodeoxycholic acid (UDCA). METHODS:
      Consecutive PBC patients were retrospectively reviewed. 25-hydroxyvitamin D
      [25(OH)D] levels were determined in frozen serum samples collected before
      initiation of UDCA treatment. Response to UDCA was evaluated by Paris-I and
      Barcelona criteria. Logistic regressions were performed to identify the treatment
      response-associated parameters. RESULTS: Among 98 patients, the mean serum
      25(OH)D concentration was 17.9 +/- 7.6 ng/mL. 25(OH)D levels decreased with
      increasing histological stage (P = 0.029) and were negatively correlated with
      bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31
      patients failed to achieve complete response according to Paris-I criteria. The
      baseline 25(OH)D level was significantly lower in nonresponders (14.8 +/- 6.4 vs.
      19.3 +/- 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated
      with an increased risk of incomplete response independent of advanced stages (OR
      = 3.93, 95% CI = 1.02-15.19, P = 0.047). Similar results were obtained when
      biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D
      levels were lower in patients who subsequently suffered death or liver
      transplantation (12.1 +/- 4.6 vs. 18.4 +/- 7.6 ng/mL, P = 0.023). CONCLUSIONS:
      25(OH)D level is associated with biochemical and histological features in PBC.
      Pre-treatment vitamin D status is independently related to subsequent response to
      UDCA. Our results suggest that vitamin D status may have important clinical
      significance in PBC.

PMID- 25982181
TI  - Emerging tyrosine kinase inhibitors for the treatment of renal cancer.
AB  - INTRODUCTION: Since both cytotoxic and cytokine therapy were not able to improve
      the prognosis of advanced renal cell carcinoma (RCC), this tumor has been a good
      model for the development of new biological agents in the past decade. Five VEGF
      receptor (VEGFR) and two mammalian target of rapamycin (mTOR) inhibitors are
      currently available for treatment of this disease but several issues need to be
      resolved such as a better definition of prognosis, the overcome of resistance and
      the best therapy for less frequent histologies. AREAS COVERED: This review
      focuses on new tyrosine kinase inhibitors (TKIs) under investigation in these
      patients. Study design, phase of investigation, result and emerging toxicities
      were reported for each molecule. Combination trials involving TKIs with other
      strategies such as immunotherapy were also covered. EXPERT OPINION: Despite the
      development of more potent and more specific VEGFR TKIs, all tumors ultimately
      develop resistance to therapy and a plateau has been reached in terms of overall
      survival. Current research effort to develop new agents aims at overcoming both
      the primary and the acquired resistance to anti-VEGFR TKIs focusing on new
      molecular pathways. The ultimate goal is not only to improve patient outcome but
      to achieve durable complete remission. Several pitfalls that have been
      responsible for failure of other compounds remain, especially the lack of strong
      predictive biomarkers and the use of inappropriate tumor assessment criteria that
      may not accurately capture response to these new therapies.

PMID- 25982182
TI  - Marinesco-Sjogren syndrome caused by a new SIL1 frameshift mutation.

PMID- 25982183
TI  - Differentiating primary central nervous system (CNS) lymphoma from "butterfly
      glioma": A case report.

PMID- 25982184
TI  - Primary atypical melanocytoma arising from the cavernous sinus in a child.
AB  - INTRODUCTION: Primary melanocytic lesions of the central nervous system originate
      from leptomeningeal melanocytes, with a spectrum ranging from well-differentiated
      benign meningeal melanocytomas to malignant melanomas. Atypical melanocytomas are
      borderline tumors, which have clinical and pathological characteristics between
      benign melanocytomas and malignant melanomas. Melanocytomas are rare in children
      and infrequently arise from the cavernous sinus. Approximately five patients with
      such an origin site have been reported. MATERIALS AND METHODS: We report a 15
      year-old girl with an atypical melanocytoma arising from the cavernous sinus. She
      underwent partial resection of the tumor and postoperative gamma knife surgery
      (GKS). She is stable 39 months after surgery. CONCLUSION: We discuss the first
      pediatric case with an intracranial atypical melanocytoma arising from the
      cavernous sinus.

PMID- 25982186
TI  - Arylnaphthalene and aryltetralin-type lignans in hairy root cultures of Linum
      perenne, and the stereochemistry of 6-methoxypodophyllotoxin and one
      diastereoisomer by HPLC-MS and NMR spectroscopy.
AB  - INTRODUCTION: Hairy root cultures of Linum sp. are an alternative for the high
      production of lignans. Linum perenne is known to produce arylnaphthalene-type
      lignans such as justicidin B, isojusticidin and diphyllin. OBJECTIVE: To
      elucidate the presence of aryltetralin-type lignan diastereoisomers, besides the
      known arylnaphthalene-type lignans, in hairy roots of Linum perenne, and to
      determine the configurations of one diastereoisomer of 6-methoxypodophyllotoxin
      (6-MPTOX). METHODS: Lignans from hairy root cultures of Linum perenne were
      extracted and separated by HPLC. Arylnaphthalene-type lignans were identified by
      LC-MS, according to the literature. Two diastereoisomers of aryltetralin-type
      lignans were analysed by mass spectrometry and NMR spectroscopy. RESULTS:
      Numerous arylnaphthalene-type lignans (diphyllin-2-hexose-pentose, diphyllin-3
      pentose and diphyllin-hexose) were identified in hairy root cultures.
      Methoxypodophyllotoxin, an aryltetralin-type lignan, was also identified, as well
      as one diastereoisomer. This aryltetralin-type lignan could be derived via 7
      hydroxymatairesinol as a hypothetical biosynthetic pathway. The stereochemical
      configurations of aryltetralin isomers were determined. CONCLUSION:
      Arylnaphthalene and two diastereoisomers of aryltetralin-type lignans are
      produced in Linum perenne hairy root cultures. Matairesinol, the precursor of
      justicidin B, also seems to be converted into 6-MPTOX via 7-hydroxymatairesinol.
      This is the first report of the stereochemical configurations of an aryltetralin
      type lignan other than podophyllotoxin (PTOX).

PMID- 25982185
TI  - Liraglutide is neurotrophic and neuroprotective in neuronal cultures and
      mitigates mild traumatic brain injury in mice.
AB  - Traumatic brain injury (TBI), a brain dysfunction for which there is no present
      effective treatment, is often caused by a concussive impact to the head and
      affects an estimated 1.7 million Americans annually. Our laboratory previously
      demonstrated that exendin-4, a long-lasting glucagon-like peptide 1 receptor (GLP
      1R) agonist, has neuroprotective effects in cellular and animal models of TBI.
      Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP
      1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI
      (mTBI). Liraglutide promoted dose-dependent proliferation in SH-SY5Y cells and in
      a GLP-1R over-expressing cell line at reduced concentrations. Pre-treatment with
      liraglutide rescued neuronal cells from oxidative stress- and glutamate
      excitotoxicity-induced cell death. Liraglutide produced neurotrophic and
      neuroprotective effects similar to those of exendin-4 in vitro. The
      cAMP/PKA/pCREB pathway appears to play an important role in this neuroprotective
      activity of liraglutide. Furthermore, our findings in cell culture were well
      translated in a weight drop mTBI mouse model. Post-treatment with a clinically
      relevant dose of liraglutide for 7 days in mice ameliorated memory impairments
      caused by mTBI when evaluated 7 and 30 days post trauma. These data cross
      validate former studies of exendin-4 and suggest that liraglutide holds
      therapeutic potential for the treatment of mTBI. Exendin-4, a long-lasting
      glucagon-like peptide 1 receptor (GLP-1R) agonist, has neuroprotective effects in
      cellular and animal models of traumatic brain injury (TBI). Here, we demonstrate
      neurotrophic and neuroprotective effects of a different GLP-1R agonist,
      liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI).
      Liraglutide promoted dose-dependent proliferation in SH-SY5Y cells and in a GLP
      1R over-expressing cell line at reduced concentrations. Pretreatment with
      liraglutide rescued neuronal cells from oxidative stress- and glutamate
      excitotoxicity-induced cell death. Liraglutide produced neurotrophic and
      neuroprotective effects similar to those of exendin-4 in vitro, likely involving
      the cAMP/PKA/pCREB pathway. Our findings in cell culture were well-translated in
      a weight-drop mTBI mouse model. Post-treatment with a clinically relevant dose of
      liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI.

PMID- 25982187
TI  - Social support among HIV-positive and HIV-negative adolescents in Umlazi, South
      Africa: changes in family and partner relationships during pregnancy and the
      postpartum period.
AB  - BACKGROUND: Pregnancy is common among adolescents in South Africa, yet the social
      experiences of adolescents during the pregnancy and postpartum period remain
      understudied in this context. We aimed to explore how adolescent women's
      discovery and disclosure of both their pregnancy and HIV status affected their
      relationships with family members and sexual partners, with a particular focus on
      whether and how support changed throughout this time period. METHODS: We
      conducted in-depth semi-structured interviews with 15 HIV-positive and HIV
      negative adolescent women who were either pregnant or had delivered in the last
      18 months from one urban clinic in Umlazi, South Africa. Interviews were
      audiotaped, transcribed, translated, and coded for analysis. RESULTS: Young women
      described stress and instability in their relationships with family and partners
      during pregnancy and the postpartum period, though prior to and during HIV-status
      disclosure women generally experienced less stress than in disclosing their
      pregnancy to family members and partners. After a destabilizing period
      immediately following pregnancy disclosure, families became and remained the
      primary source of material and emotional support for the young women. Women
      discussed heightened closeness with their partners during pregnancy, but few
      women had close relationships with their partners postpartum. Support experiences
      did not differ by HIV status. CONCLUSION: Programs should be aware of the
      relative importance of pregnancy-related concerns over HIV-related concerns in
      this population of young women. Engaging family members is critical in ensuring
      social support for this population of young pregnant women, and in encouraging
      timely initiation of antenatal care.

PMID- 25982188
TI  - Risk of deep vein thrombosis and pulmonary embolism after heart transplantation:
      clinical outcomes comparing upper extremity deep vein thrombosis and lower
      extremity deep vein thrombosis.
AB  - INTRODUCTION: Heart transplant patients have risk factors that place them at
      higher risk for acute venous thromboembolism (VTE), which includes deep vein
      thrombosis (DVT) and pulmonary embolism (PE), than the general population. We
      assessed for rate of VTE and incidence of PE-related mortality among heart
      transplant patients. MATERIALS AND METHODS: A total of 1258 heart transplant
      patients were evaluated for the development of VTE. The diagnosis of DVT was made
      by Duplex ultrasonography, and PE was diagnosed by computerized tomography
      pulmonary angiography or ventilation-perfusion radionuclide scan. PE-related
      mortality was assessed at one yr, three yr, and five yr post-transplant. RESULTS:
      A total of 117 (9.3%) patients were diagnosed with DVT, including 65 of 117
      (55.5%) with lower extremity DVT (LEDVT) and 52 of 117 (44.4%) with upper
      extremity DVT (UEDVT). A total of 24 (1.9%) patients experienced PE with seven
      (29.2%) resulting deaths. The rate of LEDVT and UEDVT was similar (55.5% vs.
      44.4%); however, the incidence of PE was greater for those with LEDVT (23.1% vs.
      7.7%; p = 0.04). Patients with PE had lower survival over the five-yr follow-up
      period compared to those with DVT only (67% vs. 81%; p = 0.51). CONCLUSION: Heart
      transplant patients have a high incidence of VTE despite current best practice,
      indicating a need for a more aggressive approach to thromboprophylaxis.

PMID- 25982189
TI  - Three-year prognosis of first-ever primary pontine hemorrhage in a hospital-based
      registry.
AB  - Our aim was to evaluate the mortality rate of primary pontine hemorrhage (PPH)
      and to determine the factors related to the prognosis. Limited data exist on the
      long-term prognosis and determinants of death in patients with PPH in China. Our
      study analyzed consecutive cases of first-ever PPH from April 2007 to March 2011
      in a hospital-based stroke registry. Mortality rates during 30 day and 3 year
      follow-ups were analyzed. We used the Kaplan-Meier method to estimate the event
      rates and binary logistic regression analysis, and Cox proportional hazard
      regression analysis to identify predictors of short-term and long-term prognosis,
      respectively. A total of 76 patients were identified, 44 (57.89%) were men. Both
      30 day and 3 year overall mortalities in men were higher than women but this
      different was not statistically significant. Coma on admission, hematoma ? 4 mL
      and a massive hemorrhage were significantly related to 30 day mortality of PPH.
      Multivariate Cox proportional hazard regression revealed that coma on admission
      (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.16-4.13; p = 0.02) and
      hematoma ? 4 mL (HR 2.23; 95% CI 1.25-3.96; p = 0.01) were independent predictors
      of 3 year mortality. In conclusion, the short-term mortality rate and factors
      related to the prognosis of Chinese patients with PPH are similar to those
      reported for other populations. A low Glasgow coma scale score on admission and a
      large hematoma volume may be related to poor 3 year prognosis after PPH.

PMID- 25982190
TI  - Field deployment of loop-mediated isothermal amplification for centralized mass
      screening of asymptomatic malaria in Zanzibar: a pre-elimination setting.
AB  - BACKGROUND: Molecular tools for detection of low-density asymptomatic Plasmodium
      infections are needed in malaria elimination efforts. This study reports results
      from the hitherto largest implementation of loop-mediated isothermal
      amplification (LAMP) for centralized mass screening of asymptomatic malaria in
      Zanzibar. METHODS: Healthy individuals present and willing to participate in
      randomly selected households in 60 villages throughout Zanzibar were screened for
      malaria by rapid diagnostic tests (RDT). In 50% of the study households,
      participants were asked to provide 60 MUL of finger-prick blood for additional
      LAMP screening. LAMP was conducted in two centralized laboratories in Zanzibar,
      by trained technicians with limited or no previous experience of molecular
      methods. The LAMP assay was performed with Loopamp(TM) MALARIA Pan/Pf Detection
      Kit (Eiken Chemical Company, Japan). Samples positive for Plasmodium genus (Pan)
      LAMP were re-tested using Plasmodium falciparum-specific LAMP kits. RESULTS:
      Paired RDT and LAMP samples were available from 3983 individuals. The prevalence
      of asymptomatic malaria was 0.5% (CI 95% 0.1-0.8) and 1.6% (CI 95% 1.1-2.2) by
      RDT and Pan-LAMP, respectively. LAMP detected 3.4 (CI 95% 2.2-5.2) times more
      Plasmodium positive samples than RDT. DNA contamination was experienced, but
      solved by repetitive decontamination of all equipment and reagents. CONCLUSIONS:
      LAMP is a simple and sensitive molecular tool, and has potential in active
      surveillance and mass-screening programmes for detection of low-density
      asymptomatic malaria in pre-elimination settings. However, in order to deploy
      LAMP more effectively in field settings, protocols may need to be adapted for
      processing larger numbers of samples. A higher throughput, affordable closed
      system would be ideal to avoid contamination.

PMID- 25982191
TI  - Defining cachexia in a renal population.

PMID- 25982193
TI  - Evaluation of the efficacy of antibacterial medical gloves in the ICU setting.
AB  - BACKGROUND: Inappropriate use of medical gloves may support microbial
      transmission. New strategies could increase the safety of medical gloves without
      the risk of patient and surface contamination. AIM: To compare the efficacy of
      synthetic antibacterial nitrile medical gloves coated with polyhexamethylen
      biguanid hydrochloride (PHMB) on the external surface with identical non
      antibacterial medical gloves in reducing glove contamination after common patient
      care measures in an intensive care unit (ICU) setting. METHODS: ICU staff wore
      either standard or antibacterial gloves during patient care activities. The
      number of bacteria on gloves was measured semi-quantitatively immediately after
      the performance of four clinical activities. FINDINGS: There was a significant
      difference in mean bacterial growth [colony-forming units (cfu)] between control
      gloves and antibacterial gloves {60 [standard deviation (SD) 23] vs 16 (SD 23)
      cfu/glove imprint, P < 0.001}. In three of the four clinical activities
      (intravenous fluid handling, oral toilet and physiotherapy), the antibacterial
      gloves had significantly less bacterial contamination compared with the control
      gloves (P = 0.011 and <0.001, respectively). Although antibacterial gloves showed
      lower bacterial contamination after changing linen compared with control gloves,
      the difference was not significant (P = 0.311). CONCLUSION: This study showed
      that use of antibacterial medical gloves significantly reduced bacterial
      contamination after typical patient care activities in 57% of the investigated
      clinical activities (P < 0.01). The use of antibacterial medical gloves may
      support reduction of cross-contamination in the ICU setting.

PMID- 25982194
TI  - Potential for the enhanced detection, identification, and subsequent treatment of
      periprosthetic joint infection using MALDI-TOF MS analysis of sonicate fluid.

PMID- 25982195
TI  - Supercubooctahedron (Cs6Cl)2Cs5[Ga15Ge9Se48] Exhibiting Both Cation and Anion
      Exchange.
AB  - A novel type of supertetrahedral connectivity is exhibited by the 72-atom
      discrete supercubooctahedron in (Cs6Cl)2Cs5[Ga15Ge9Se48] (1), which undergoes
      both cation and anion exchange, as revealed by unambiguous single-crystal X-ray
      diffraction data. Electronic-structure studies helped to understand the Ge/Ga
      distribution.

PMID- 25982196
TI  - Analysis of oligosaccharide sequences of trace Caulophyllum robustum saponins by
      direct infusion multiple-stage tandem mass spectrometry.
AB  - The saponins in Caulophyllum robustum have not yet been fully characterized.
      Furthermore these saponins are often present in trace amounts and are
      structurally complex. Here, a simple direct infusion electrospray ion trap
      multiple-stage tandem mass spectrometry (DI-ESI-IT-MS(n)) method was described
      for the characterization of trace C. robustum saponins. Eight reference saponins
      from the C. robustum hairy root were investigated by DI-ESI-IT-MS(n) in positive
      ion mode. Some fragmentation approaches were proposed through analysis of the
      [M+Na](+) ions: (1) preferential cleavage of the C-28 ester glycosidic bond to
      provide complementary [Y0alpha+Na](+) and [Balpha+Na](+) ions for bidesmosidic
      saponins; (2) diagnostically neutral loss of CO2 from free carboxyl groups at C
      28 for monodesmosidic saponins; and (3) the ion intensity ratio between
      [C2beta+Na](+) and [B2beta+Na](+), which is sensitive to the structural
      differences between the two isomeric beta-sugar chains (Glc -> (2)Ara and Glc ->
      (3)Ara). The DI-ESI-IT-MS(n) method was successfully used for the analysis of
      trace C. robustum saponins with [M+Na](+) ions at m/z 1745.6, 1729.5, 1583.7,
      1567.7, 1421.7 and 1405.7. This article highlights the discovery and
      identification of complex alpha- and beta-oligosaccharide moieties in
      Caulophyllum saponins by glycosidic product ions along with cross ring cleavage
      product ions. Five oligosaccharide moieties were unambiguously or tentatively
      identified as Rha -> (4)Glc -> (6)Glc -> (4)Rha -> (4)Glc -> (6)Glc, Glc ->
      (4)Glc -> (6)Glc -> (4)Rha -> (4)Glc -> (6)Glc, Rha -> Glc -> Glc (Glc) ->
      (2,3)Ara, Glc -> Glc (Glc) -> (2,3)Ara and Glc (Glc) -> (2,3)Ara. Accuracy of the
      analytical procedure was demonstrated by structural identification of two
      saponins isolated using 1D and 2D-NMR spectroscopy. The DI-ESI-IT-MS(n) method
      facilitates rapid discovery and analysis of trace Caulophyllum saponins and is a
      powerful and practical tool for structural characterization of complex
      oligosaccharide moieties in triterpene saponins.

PMID- 25982197
TI  - High performance liquid chromatography-electrospray ionization-mass spectrometry
      with programmed ionization mode switching and time segment scanning approach for
      quantifying multi-components in traditional complex herbal medicines, Qiong-Yu
      Gao as an example.
AB  - An improved high performance liquid chromatography-electrospray ionization-mass
      spectrometry (HPLC-ESI-MS) method was developed to quantitatively evaluate the
      holistic quality of traditional complex herbal medicines (CHMs). Qiong-Yu-Gao
      (QYG), a classical CHM consisting of Rehmanniae Radix, Poriae and Ginseng Radix,
      was used as an example. Thirty-eight major components (including six pairs of
      epimers/isomers) belonging to five chemical types, i.e., iridoid glycosides,
      phenethylacohol glycosides, furfural derivatives, ginsenosides and triterpenoid
      acids, were selected as marker compounds. Programmed ionization mode switching
      and time segment scanning were designed to improve the sensitivity of the MS
      detection concerning the diverse chemical features of the analytes. The reference
      compounds of the analytes were individually injected directly into MS to optimize
      the ionization cone voltage and to select monitoring ion of each analyte. Nine
      channels with eight time segments were determined for monitoring the thirty-eight
      analytes, among which six were detected in positive and thirty-two in negative
      ion modes respectively. Higher signal-to-noise ratios of the analytes were
      achieved when compared with full time scanning. In addition, the linearity,
      precision, accuracy and stability of the method were also validated. The
      established method was applied for the quantitative evaluation of QYG samples
      prepared with three different methods. Obvious difference in the contents of
      thirty-eight components, in particular the original ginsenosides, degraded
      ginsenosides and furfural derivatives, was found among these QYG samples. All
      these results demonstrated that the established HPLC-ESI-MS with programmed
      ionization mode switching and time segment scanning approach is very suitable for
      the standardization investigation of CHMs. 

PMID- 25982198
TI  - Current technologies for the endoscopic assessment of duodenal villous pattern in
      celiac disease.
AB  - Currently, standard endoscopy is not considered enough reliable for the
      evaluation of celiac disease, neither to drive biopsy sampling. The diagnostic
      reliability of the endoscopic assessment of celiac disease has been increased by
      the recent advancement of software and hardware technologies. Several endoscopic
      technologies have been investigated so far for the diagnostic evaluation of
      celiac disease, including: water-immersion techniques, dye-based and dye-less
      chromoendoscopy techniques (Narrow band imaging; Fujinon Intelligeng Chromo
      Endoscopy; I-scan); optical coherence tomography; confocal laser endomicroscopy;
      high-resolution magnification endoscopy; videocapsule endoscopy; enteroscopy.
      Such a technologic improvement brought us to higher diagnostic possibilities in
      the evaluation and management of CD. A wider application of advanced diagnostic
      endoscopic techniques is therefore warranted to decrease the number of
      misdiagnoses and related healthcare costs of celiac disease. 

PMID- 25982199
TI  - An efficient detection of epileptic seizure by differentiation and spectral
      analysis of electroencephalograms.
AB  - Epilepsy is a critical neurological disorder resulting from abnormal hyper
      excitability of neurons in the brain. Studies have shown that epilepsy can be
      detected in electroencephalography (EEG) recordings of patients suffering from
      seizures. The performance of EEG-based epileptic seizure detection relies largely
      on how well one can extract features from an EEG that characterize seizure
      activity. Conventional feature extraction methods using time-series analysis,
      spectral analysis and nonlinear dynamic analysis have advanced in recent years to
      improve detection. The computational complexity has also increased to obtain a
      higher detection rate. This study aimed to develop an efficient feature
      extraction method based on Hjorth's mobility to reduce computational complexity
      while maintaining high detection accuracy. A new feature extraction method was
      proposed by computing the spectral power of Hjorth's mobility components, which
      were effectively estimated by differentiating EEG signals in real-time. Using EEG
      data in five epileptic patients, this method resulted in a detection rate of
      99.46% between interictal and epileptic EEG signals and 99.78% between normal and
      epileptic EEG signals, which is comparable to most advanced nonlinear methods.
      These results suggest that the spectral features of Hjorth's mobility components
      in EEG signals can represent seizure activity and may pave the way for developing
      a fast and reliable epileptic seizure detection method.

PMID- 25982200
TI  - Developing non-technical ward-round skills.
AB  - BACKGROUND: Conducting clinical 'rounds' is one of the most onerous and important
      duties that every junior doctor is expected to perform. There is evidence that
      newly qualified doctors are not adequately prepared by their undergraduate
      experiences for this task. The aim of this study was to analyse the challenges
      pertaining to non-technical skills that students would face during ward rounds,
      and to create a model that facilitates the transition from medical student to
      doctor. METHODS: A total of 217 final-year medical students completed a simulated
      ward round. Free-text responses were analysed using template analysis applying an
      a priori template developed from the literature by the research team. This drew
      on the generic categories of non-technical skills suggested by Flin et al.
      RESULTS: Ninety-seven per cent of students agreed or strongly agreed that the
      simulated ward round improved their insight into the challenges of ward rounds
      and their perceived ability to work efficiently as an active member of the ward
      round. The responding students (206) submitted written feedback describing the
      learning that they planned to use: 800 learning points were recorded, and all
      could be categorised into one of seven non-technical skills. Conducting clinical
      'rounds' is one of the most onerous and important duties that every junior doctor
      is expected to perform DISCUSSION: We believe that improved task efficiency and
      insight into the challenges of the ward round gained by medical students will
      lead to an enhancement in performance during clinical rounds, and will have a
      positive impact on patient safety. We would suggest that undergraduate medical
      schools consider this model in the preparation for the clinical practice element
      of the curriculum.

PMID- 25982201
TI  - Recruiting polycomb to chromatin.
AB  - Polycomb group (PcG) proteins are key regulators in establishing a
      transcriptional repressive state. Polycomb Repressive Complex 2 (PRC2), one of
      the two major PcG protein complexes, is essential for proper differentiation and
      maintenance of cellular identity. Multiple factors are involved in recruiting
      PRC2 to its genomic targets. In this review, we will discuss the role of DNA
      sequence, transcription factors, pre-existing histone modifications, and RNA in
      guiding PRC2 towards specific genomic loci. The DNA sequence itself influences
      the DNA methylation state, which is an important determinant of PRC2 recruitment.
      Other histone modifications are also important for PRC2 binding as PRC2 can
      respond to different cellular states via crosstalk between histone modifications.
      Additionally, PRC2 might be able to sense the transcriptional status of genes by
      binding to nascent RNA, which could also guide the complex to chromatin. In this
      review, we will discuss how all these molecular aspects define a local chromatin
      state which controls accurate, cell-type-specific epigenetic silencing by PRC2.
      This article is part of a Directed Issue entitled: Epigenetics dynamics in
      development and disease. 

PMID- 25982202
TI  - Role of transcription factor Sp1 in the 4-O-methylhonokiol-mediated apoptotic
      effect on oral squamous cancer cells and xenograft.
AB  - Recently, biphenolic components derived from the Magnolia family have been
      studied for anti-cancer, anti-stress, and anti-inflammatory pharmacological
      effects. However, the pharmacological mechanism of action of 4-O-methylhonokiol
      (MH) is not clear in oral cancer. The aim of this study was to investigate the
      role of MH in apoptosis and its molecular mechanism in oral squamous cell
      carcinoma (OSCC) cell lines, HN22 and HSC4, as well as tumor xenografts. Here, we
      demonstrated that MH decreased cell growth and induced apoptosis in HN22 and HSC4
      cells through the regulation of specificity protein 1 (Sp1). We employed several
      experimental techniques such as MTS assay, DAPI staining, PI staining, Annexin
      V/7-ADD staining, RT-PCR, western blot analysis, immunocytochemistry,
      immunohistochemistry, TUNEL assay and in vivo xenograft model analysis. MH
      inhibited Sp1 protein expression and reduced Sp1 protein levels via both
      proteasome-dependent protein degradation and inhibition of protein synthesis in
      HN22 and HSC4 cells; MH did not alter Sp1 mRNA levels. We found that MH directly
      binds Sp1 by Sepharose 4B pull-down assay and molecular modeling. In addition,
      treatment with MH or knocking down Sp1 expression suppressed oral cancer cell
      colony formation. Moreover, MH treatment effectively inhibited tumor growth and
      Sp1 levels in BALB/c nude mice bearing HN22 cell xenografts. These results
      indicated that MH inhibited cell growth, colony formation and also induced
      apoptosis via Sp1 suppression in OSCC cells and xenograft tumors. Thus, MH is a
      potent anti-cancer drug candidate for oral cancer. 

PMID- 25982203
TI  - Dynamic changes of DNA epigenetic marks in mouse oocytes during natural and
      accelerated aging.
AB  - Aging is a complex time-dependent biological process that takes place in every
      cell and organ, eventually leading to degenerative changes that affect normal
      biological functions. In the past decades, the number of older parents has
      increased significantly. While it is widely recognized that oocyte aging poses
      higher birth and reproductive risk, the exact molecular mechanisms remain largely
      elusive. DNA methylation of 5-cytosine (5mC) and histone modifications are among
      the key epigenetic mechanisms involved in critical developmental processes and
      have been linked to aging. However, the impact of oocyte aging on DNA
      demethylation pathways has not been examined. The recent discovery of Ten-Eleven
      Translocation (TET) family proteins, thymine DNA glycosylase (TDG) and the
      demethylation intermediates 5hmC, 5fC and 5caC has provided novel clues to
      delineate the molecular mechanisms in DNA demethylation. In this study, we
      examined the cellular level of modified cytosines (5mC, 5hmC, 5fC and 5caC) and
      Tet/Tdg expression in oocytes obtained from natural and accelerated oocyte aging
      conditions. Here we show all the DNA demethylation marks are dynamically
      regulated in both aging conditions, which are associated with Tet3 over
      expression and Tdg repression. Such an aberrant expression pattern was more
      profound in accelerated aging condition. The results suggest that DNA
      demethylation may be actively involved in oocyte aging and have implications for
      development of potential drug targets to rejuvenate aging oocytes. This article
      is part of a Directed Issue entitled: Epigenetics dynamics in development and
      disease. 

PMID- 25982204
TI  - Headache determines quality of life in idiopathic intracranial hypertension.
AB  - BACKGROUND: The effect of idiopathic intracranial hypertension (IIH) on quality
      of life (QOL) is poorly understood. Our objectives were to compare QOL in IIH to
      the normal UK population; to investigate QOL changes with treatment of IIH, using
      a weight loss intervention, and to determine which clinical factors influence
      QOL. METHODS: This was a prospective cohort evaluation of QOL, using the 36-Item
      Short Form (SF-36) Health Survey questionnaire, before and after a therapeutic
      dietary intervention which resulted in significant reduction in body mass index
      (BMI), intracranial pressure (ICP), papilloedema, visual acuity, perimetric mean
      deviation (Humphrey 24-2) and headache (six-item headache impact test (HIT-6) and
      headache diary). Baseline QOL was compared to an age and gender matched
      population. The relationship between each clinical outcome and change in QOL was
      evaluated. RESULTS: At baseline, QOL was significantly lower in IIH compared to
      an age and gender matched population in most domains, p < 0.001. Therapeutic
      weight loss led to a significant improvement in 10 out of 11 QOL domains in
      conjunction with the previously published data demonstrating significant
      improvement in papilloedema, visual acuity, perimetry and headache (p < 0.001)
      and large effect size. Despite significant improvement in clinical measures only
      headache correlated significantly (p < 0.001) with improving QOL domains.
      CONCLUSIONS: QOL in IIH patients is significantly reduced. It improved with
      weight loss alongside significant improvement in clinical measures and headache.
      However, headache was the only clinical outcome that correlated with enhanced
      QOL. Effective headache management is required to improve QOL in IIH.

PMID- 25982205
TI  - Immunological features of T cells induced by human telomerase reverse
      transcriptase-derived peptides in patients with hepatocellular carcinoma.
AB  - Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme required for
      telomere elongation. In this study, we investigated the safety and immunogenicity
      of an hTERT-derived peptide (hTERT461) as a vaccine and characterized the hTERT
      specific T cell responses induced. Fourteen hepatocellular carcinoma (HCC)
      patients were enrolled in the study. The hTERT-derived peptide was emulsified in
      incomplete Freund's adjuvant and administered via subcutaneous immunization three
      times biweekly. The maximum toxicity observed was grade 2 according to the common
      terminology criteria and mainly consisted of skin reactions at the site of
      vaccination. The vaccination induced hTERT-specific immunity in 71.4% of patients
      and 57.1% of patients administered with hTERT461 peptide-specific T cells could
      prevent HCC recurrence after vaccination. In phenotypic analysis, the post
      vaccinated increase in hTERT-specific T cells was due to an increase in cells
      with the effector memory phenotype, with the potential to produce multiple
      cytokines. Seven hTERT-specific T cell receptors were obtained from the
      vaccinated patients, showing their cytotoxic activities to hTERT-derived peptide
      bearing cells. In conclusion, the safety and effects of immune boosting by
      hTERT461 peptide have shown the potential of the peptide to provide clinical
      benefits in HCC patients. 

PMID- 25982207
TI  - Updates on Aspergillus, Pneumocystis and other opportunistic pulmonary mycoses.
AB  - Mycoses are serious diseases with potentially fatal outcome. The introduction of
      immunosuppressive treatments and life support techniques has led to a growing
      prevalence of different degrees of immunosuppression. Compromised immune response
      is the primary risk factor for the development of opportunistic mycoses. Early
      diagnosis and treatment are crucial for improving prognosis. However, isolation
      in cultures or identification using antigen detection techniques cannot
      distinguish between colonization and invasive infection, and the clinical status
      of the patient often prevents biopsy sampling. Clinicians thus find themselves in
      an uncertain position, requiring them to quickly recognize clinical and
      radiological signs and interpret microbiological results in context. The aim of
      this review is to provide a general overview of the profile of patients
      susceptible to these infections, the role of the immune system and, in more
      detail, the major diagnostic developments that have gained most acceptance and
      recognition among the scientific community. 

PMID- 25982206
TI  - Bevacizumab radiosensitizes non-small cell lung cancer xenografts by inhibiting
      DNA double-strand break repair in endothelial cells.
AB  - The aims of this study were to evaluate the effects of biweekly bevacizumab
      administration on a tumor microenvironment and to investigate the mechanisms of
      radiosensitization that were induced by it. Briefly, bevacizumab was administered
      intravenously to Balb/c nude mice bearing non-small cell lung cancer (NSCLC)
      H1975 xenografts; in addition, bevacizumab was added to NSCLC or endothelial
      cells (ECs) in vitro, followed by irradiation (IR). The anti-tumor efficacy, anti
      angiogenic efficacy and repair of DNA double-strand breaks (DSBs) were evaluated.
      The activation of signaling pathways was determined using immunoprecipitation
      (IP) and WB analyses. Finally, biweekly bevacizumab administration inhibited the
      growth of H1975 xenografts and induced vascular normalization periodically.
      Bevacizumab more significantly increased cellular DSB and EC apoptosis when
      administered 1 h prior to 12 Gy/1f IR than when administered 5 days prior to IR,
      thereby inhibiting tumor angiogenesis and growth. In vitro, bevacizumab more
      effectively increased DSBs and apoptosis prior to IR and inhibited the clonogenic
      survival of ECs but not NSCLC cells. Using IP and WB analyses, we confirmed that
      bevacizumab can directly inhibit the phosphorylation of components of the
      VEGR2/PI3K/Akt/DNA-PKcs signaling pathway that are induced by IR in ECs. In
      conclusion, bevacizumab radiosensitizes NSCLC xenografts mainly by inhibiting DSB
      repair in ECs rather than by inducing vascular normalization. 

PMID- 25982208
TI  - Purtscher retinopathy: to treat or not to treat?
AB  - PURPOSE: To report a case of Purtscher retinopathy and its therapeutic approach.
      METHODS: In this observational case report, complete ophthalmologic examination
      was performed, including best-corrected visual acuity (BCVA) testing, slit-lamp
      biomicroscopy, dilated fundus examination, spectral-domain optical coherence
      tomography (OCT), fluorescein angiography (FA), and Humphrey 24-2 visual field
      testing. RESULTS: The patient complained of right eye diminished visual acuity 48
      hours after a car accident, with severe thoracic and abdominal blunt trauma but
      no direct ocular trauma. The BCVA was counting fingers at 1 meter, anterior
      segment examination was unremarkable, and the fundus showed cotton-wool spots and
      Purtscher flecken. Macular OCT revealed subretinal fluid with neurosensorial
      retinal detachment. The FA showed peripapillary and parafoveal leakage and visual
      field testing presented a central scotoma. We opted for an observation-only
      approach. Follow-up revealed a progressive reabsorption of the subretinal fluid
      with complete resolution of the macular neurosensorial retinal detachment after 2
      weeks. After 2 months of follow-up, BCVA was 20/25 and the OCT revealed atrophic
      changes, with no subretinal fluid. The favorable outcome in terms of BCVA
      persisted at 4 and 6 months follow-up, although the central scotoma did not
      improve significantly. CONCLUSIONS: The characterization of both acute and late
      stage lesions provides a valuable insight to a better characterization of this
      rare disease. Despite a favorable response with a conservative therapeutic
      approach, structural and functional late stage sequelae influence the final
      visual outcome.

PMID- 25982209
TI  - Multimodality imaging of retinal astrocytoma.
AB  - PURPOSE: Cross-characterization of retinal astrocytomas (RA) using ocular
      diagnostic imaging techniques. METHODS: Fundus photography, fluorescein
      angiography, optical coherence tomography, fundus autofluorescence images, and
      ultrasonography were used to define characteristics of RA. RESULTS: Thirteen
      patients had sporadic RA and 12 had tuberous sclerosis. Of the latter, 1 patient
      had multiple (n = 14), bilateral tumors and was excluded so as not to skew the
      analysis. Of those patients with a solitary RA, 63% were juxtapapillary. All were
      white to yellow. A mulberry-shaped surface was observed in 33%. Fluorescein
      angiography revealed intrinsic tumor vessels and late diffuse tumor staining in
      42%. Optical coherence tomography revealed cells spreading from the tumor surface
      into the vitreous (75%), intraretinal fluid (25%), and multiple, ovoid
      hypolucencies within the tumor stroma (54%). Fundus autofluorescent imaging
      revealed that hypolucencies were hyperautofluorescent and solid tumor stroma
      appeared hypoautofluorescent. B-scan imaging revealed moderate to high internal
      tumor reflectivity (100%) with orbital shadowing (46%). Optical coherence
      tomography revealed a mean tumor thickness of 0.8 mm. Ultrasound imaging showed a
      mean thickness of 1.4 mm (range 1.0-1.7). Of the 21 patients subsequently
      followed in our centers, no tumor growth was noted (mean 54 months, range 1-96).
      CONCLUSIONS: This study reveals unique characteristics of RA and suggests that RA
      were most commonly amelanotic, moderate to high echoic, <=1.7 mm in thickness,
      near the optic disc, and nonprogressive. When observed, a mulberry-shaped surface
      was pathognomonic.

PMID- 25982210
TI  - Long-term (>8 years) evaluation of progression in patients with low-pressure
      glaucoma.
AB  - PURPOSE: To describe the long-term clinical course of patients with low-pressure
      glaucoma (LPG) and to assess the risk factors for disease progression. METHODS:
      The Wills Eye Glaucoma Research Center retrospectively reviewed the charts of LPG
      patients with documented follow-up of >8 years between 2000 and 2013. Medical
      records were evaluated for systemic diseases, family history of glaucoma, best
      corrected visual acuity, refractive error, treatments, central corneal thickness
      (CCT), intraocular pressure (IOP), IOP change after pupil dilation, optic disc
      evaluation, visual field (VF) mean deviation (MD), VF grading, and time to
      progression. Progression was determined when both disc and VF appeared to have
      worsened. RESULTS: From 850 charts classified as LPG between 2000 and 2013, 49
      eyes of 49 patients were included in our analysis. The mean ( +/- SD) follow-up
      time was 9.3 ( +/- 1.9) years. Glaucoma progressed in 25 eyes and remained stable
      in 24 eyes over the follow-up period. Eyes with progression had higher peak IOP
      (p = 0.043). There was a trend towards progression in patients with thinner CCT
      (p = 0.085) and disc hemorrhage (p = 0.098). Estimated annual change in MD was 
      0.57 dB in the progressing group and -0.10 dB in the stable group (p<0.0001).
      CONCLUSIONS: Nearly half of the patients with LPG showed glaucoma progression
      despite treatment after >8 years. High peak IOP was a significant risk factor for
      progression. Identifying patients at risk may warrant closer follow-up and more
      aggressive treatment in order to preserve visual function in patients with LPG.

PMID- 25982211
TI  - Vogt-Koyanagi-Harada disease after stapedotomy.
AB  - PURPOSE: To report on Vogt-Koyanagi-Harada disease that occurred after
      stapedotomy. METHODS: Case report. RESULTS: A 46-year-old woman developed
      bilateral choroiditis, papillitis, and serous retinal detachment 10 days after an
      uneventful surgical stapedotomy. The diagnosis was confirmed on the basis of the
      clinical features, fundus fluorescein angiography and optical coherence
      tomography findings, and a clinical course with subsequent involvement of the
      anterior segment, uveitis relapses with serous retinal detachment, and negative
      laboratory work-up for uveitis. CONCLUSIONS: Vogt-Koyanagi-Harada disease may
      appear after an uneventful surgical intervention of stapedotomy, suggesting that
      surgical trauma in the inner ear, a melanocyte-containing organ, may induce an
      inflammatory response within the eye.

PMID- 25982212
TI  - High-intensity focused ultrasound treatment in refractory glaucoma patients:
      results at 1 year of prospective clinical study.
AB  - PURPOSE: To evaluate the safety and efficacy of the ultrasonic circular cyclo
      coagulation procedure using high-intensity focused ultrasound by a miniaturized
      annular device containing 6 piezoceramic transducers in patients with refractory
      glaucoma. METHODS: This was a prospective interventional noncomparative study of
      20 eyes of 20 patients with refractory glaucoma. All eyes were treated with 6
      activated transducers operating at 21 MHz. Ultrasound biomicroscopy and a
      complete ophthalmic examination were performed before the procedure and at 1 day,
      1 week, and 1, 3, 6, and 12 months after the procedure. Primary outcomes were
      surgical success (defined as intraocular pressure (IOP) reduction from baseline
      >=20% and IOP >5 mm Hg) at the last follow-up visit. Secondary outcomes were mean
      IOP at each follow-up visit compared to baseline, medication use, complications,
      and re-interventions. RESULTS: Intraocular pressure was significantly reduced
      (p<0.01) from a mean preoperative value of 36.4 +/- 5.7 mm Hg to a mean
      postoperative value of 22.5 +/- 10.3 mm Hg at 12 months. Four patients needed to
      be re-treated. The mean IOP reduction achieved was 38%. Surgical success was
      achieved in 13 of 20 eyes (65%). No major intraoperative or postoperative
      complications occurred. CONCLUSIONS: Ultrasonic circular cyclo-coagulation using
      high-intensity focused ultrasound delivered by a circular miniaturized device
      containing 6 piezoceramic transducers is an effective and well-tolerated method
      to reduce IOP in patients with refractory glaucoma.

PMID- 25982213
TI  - Meta-analysis of surgical approaches to the treatment of parotid pleomorphic
      adenomas and recurrence rates.
AB  - INTRODUCTION: Different types of surgical management of pleomorphic adenoma of
      the parotid gland are associated with different recurrence rates. MATERIAL AND
      METHODS: A systematic review of literature until 2014 with meta-analysis was
      conducted. Inclusion criteria were original studies of patients with surgical
      management for pleomorphic adenoma of the parotid gland and recurrence rates,
      with a median follow-up period of 5 years. The Newcastle-Ottawa Quality
      Assessment Scale (NOQAS) was used to assess the quality. RESULTS: Sixteen studies
      were included. Four studies show a low recurrence rate (0.01, 95% confidence
      interval [CI] = 0.00-0.02) after total parotidectomy. Twelve studies show a low
      recurrence rate (0.02, 95% CI = 0.01-0.03) after superficial parotidectomy. Six
      studies show a low recurrence rate (0.02, 95% CI = 0.01-0.04) after limited
      parotidectomy. Six studies demonstrate a low recurrence rate (0.01, 95% CI = 0.00
      0.04) after extracapsular dissection. Five studies report a low-to-medium
      recurrence rate (0.08, 95% CI = 0.03-0.14) after extracapsular enucleation.
      CONCLUSION: Information about recurrence rates, times of recurrence in relation
      to type of surgical treatment, and significance of capsule rupture is very poor.
      With regard to recurrence rates and surgical approaches, the types of operations
      that show the lowest recurrence rate are total parotidectomy and extracapsular
      dissection. Controversies over surgical treatment of PA of parotid gland remain,
      and the safest surgical method for the removal of this tumors has not been
      identified.

PMID- 25982215
TI  - Discordance between Risk Factors and Coronary Artery Calcium: Implications for
      Guiding Treatment Strategies in Primary Prevention Settings.
AB  - Preventive efforts including smoking cessation campaigns, increased awareness of
      healthy lifestyle habits, risk factor modification, and the appropriate use of
      statins have been successful in reducing cardiovascular mortality over the last
      decade. The coronary artery calcium (CAC) scan has reliably been an additive
      predictor to traditional risk estimation methods, partly because of the
      heterogeneity between risk factor burden and atherosclerotic burden. The focus of
      this review is to highlight this heterogeneity by focusing on groups in which
      risk factor burden and subclinical atherosclerosis burden, as measured by CAC,
      are discordant. In high-risk groups with 0 CAC, the event rates are consistently
      low; in low-risk groups with elevated CAC (CAC>100), the event rates are
      consistently high. We conclude with our clinical perspective of the considerable
      heterogeneity between risk factors and atherosclerotic burden in the context of
      the 2013 ACC/AHA cholesterol treatment and risk assessment guidelines. 

PMID- 25982216
TI  - Low Fitness in Midlife: A Novel Therapeutic Target for Heart Failure with
      Preserved Ejection Fraction Prevention.
AB  - Heart failure (HF) with preserved ejection fraction (HFpEF) is common and
      recalcitrant to any medical therapy, highlighting the need for novel strategies
      focused on its prevention. Recent studies have shown that low cardiorespiratory
      fitness (CRF) in middle age identifies a subgroup of individuals at particularly
      high risk for HF, particularly HFpEF. These findings suggest that low CRF in
      middle age represents an upstream marker for late-life HFpEF. Furthermore,
      evidence from recent epidemiological studies suggests that low CRF associated
      risk for HFpEF appears to be modifiable with improvement in CRF. The primary
      objective of this review is to provide an overview of the potential mechanisms
      through which exercise training and improvement in CRF may protect against the
      transition from a low fit stage to clinical HFpEF among at-risk sedentary, middle
      age adults. 

PMID- 25982214
TI  - International study of perceived neighbourhood environmental attributes and Body
      Mass Index: IPEN Adult study in 12 countries.
AB  - BACKGROUND: Ecological models of health behaviour are an important conceptual
      framework to address the multiple correlates of obesity. Several single-country
      studies previously examined the relationship between the built environment and
      obesity in adults, but results are very diverse. An important reason for these
      mixed results is the limited variability in built environments in these single
      country studies. Therefore, the aim of this study was to examine associations
      between perceived neighbourhood built environmental attributes and BMI/weight
      status in a multi-country study including 12 environmentally and culturally
      diverse countries. METHODS: A multi-site cross-sectional study was conducted in
      17 cities (study sites) across 12 countries (Australia, Belgium, Brazil, China,
      Colombia, Czech Republic, Denmark, Mexico, New Zealand, Spain, the UK and USA).
      Participants (n = 14222, 18-66 years) self-reported perceived neighbourhood
      environmental attributes. Height and weight were self-reported in eight
      countries, and measured in person in four countries. RESULTS: Three environmental
      attributes were associated with BMI or weight status in pooled data from 12
      countries. Safety from traffic was the most robust correlate, suggesting that
      creating safe routes for walking/cycling by reducing the speed and volume of
      traffic might have a positive impact upon weight status/BMI across various
      geographical locations. Close proximity to several local destinations was
      associated with BMI across all countries, suggesting compact neighbourhoods with
      more places to walk related to lower BMI. Safety from crime showed a curvilinear
      relationship with BMI, with especially poor crime safety being related to higher
      BMI. CONCLUSIONS: Environmental interventions involving these three attributes
      appear to have international relevance and focusing on these might have
      implications for tackling overweight/obesity.

PMID- 25982217
TI  - Chemical prophylaxis to prevent venous thromboembolism in morbid obesity:
      literature review and dosing recommendations.
AB  - Pharmacologic prophylaxis of deep vein thrombosis and venous thromboembolism
      (VTE) is an important aspect of medical care, particularly in the inpatient
      setting. Low-molecular weight heparins, heparin, and fondaparinux are commonly
      used agents to prevent VTE, each of which has well established dosing regimens in
      patients with normal body mass index. Dosing of these medications in morbidly
      obese populations (BMI > 40 kg/m(2)) is not as clearly defined in guidelines.
      This article reviews published data to support specific dosing regimens and
      monitoring strategies of these agents in this population. The most validated
      parenteral agent to prevent VTE in morbidly obese hospitalized patients is
      enoxaparin, dosed at 40 mg subcutaneously (SC) twice daily. If unfractionated
      heparin is utilized for prophylaxis in morbidly obese patients, a dose of 7500
      units SC three times daily should be considered. Monitoring of anti-factor Xa
      levels to guide prophylactic dosing is an option, although the utility of this
      lab test is limited, as target anti-Xa ranges for VTE prophylaxis have not been
      universally defined and trials have not shown a clear link between anti-factor Xa
      levels and bleeding or thrombotic events. Additional studies are needed to
      clearly define the most appropriate dosing strategies in patients with moderate
      obesity (BMI 35-40 mg/m(2)) and those with extreme obesity (BMI > 60 mg/m(2)).

PMID- 25982218
TI  - Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis
      (IAP).
AB  - Exosomes are endosomal-derived nanovesicles released by normal and tumor cells
      which have been shown to transfer functionally active protein, lipids, mRNAs and
      miRNAs between cells. Varying in molecular profiles, biological roles, functional
      roles and protein contents, exosomes have been described as "multi-purpose
      carriers" playing a role in supporting the survival and growth of tumor cells.
      The IAP Survivin has been found to be present in tumor exosomes. However, the
      existence of other IAPs in tumor exosomes is still unknown. Survivin, cIAP1,
      cIAP2 and XIAP mRNA and protein are differently expressed in a panel of tumor
      cell lines: DLCL2, HeLa, MCF-7, Panc-1, and PC3. Exosomes were isolated from
      conditioned media collected from the cells from which RNA and protein were
      extracted. Our results provide evidence that like Survivin, XIAP, cIAP1 and cIAP2
      proteins are found in tumor exosomes. The mRNA expression, however, is
      differentially expressed across the tumor cell lines. The presence of these
      bioactive molecules in exosomes may not only serve as warning signals, but also
      play a role in providing protection to the cancer cells against changes that are
      constantly occurring in the tumor microenvironment. 

PMID- 25982219
TI  - In vitro assays and clinical trials in red blood cell aging: Lost in translation.
AB  - The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse
      outcomes when transfusing long-term-stored EC are highly controversial issues.
      Whereas the definition of a short-term-stored EC or a long-term-stored EC is
      unclear in clinical trials, data based on in vitro storage assays can help
      defining a limit in addition of the expiration date. The present review merges
      together these data in order to highlight an EC age cut-off and points out
      potential misleading consideration. The analysis of in vitro data highlights the
      presence of reversible and irreversible storage lesions and demonstrates that red
      blood cells (RBC) exhibit two limits during storage: one around 2 weeks and
      another one around 4 weeks of storage. Of particular importance, the first
      lesions to appear, i.e. the reversible ones, are per se reversible once
      transfused, whereas the irreversible lesions are not. In clinical trials, the EC
      age cut-off for short-term storage is in general fewer than 14 days (11 +/- 4
      days) and more disperse for long-term-stored EC (17 +/- 13 days), regardless the
      clinical outcomes. Taking together, EC age cut-off in clinical trials does not
      totally fall into line of in vitro aging data, whereas it is the key criteria in
      clinical studies. Long-term-stored EC considered in clinical trials are not
      probably old enough to answer the question: "Does transfusion of long-term-stored
      EC (older than 4 weeks) result in worse clinical outcomes?" Depending on ethical
      concerns and clinical practices, older EC than currently assayed in clinical
      trials should have to be considered. These two worlds trying to understand the
      aging of erythrocytes and the impact on patients do not seem to speak the same
      language. 

PMID- 25982220
TI  - Tracheal intubation in patients with anticipated difficult airway using Boedeker
      intubation forceps and McGrath videolaryngoscope.
AB  - BACKGROUND: Videolaryngoscopes with sharp angulated blades improve the view of
      the vocal cords but this does not necessarily result in higher success rates of
      intubation The aim of this study was to evaluate the efficacy of using Boedeker
      intubation forceps in conjunction with McGrath Series 5 Videolaryngoscope (MVL)
      in patients with predictors for difficult intubation. METHODS: The study was
      conducted at the Department of Anaesthesia, Copenhagen University Hospital from
      September to December 2013. Patients with one or more predictors of difficult
      intubation scheduled for general anaesthesia were assessed for eligibility.
      Patients were intubated using Boedeker intubation forceps and MVL. The primary
      endpoint was time to intubation. The secondary endpoints were intubation success
      rate, number of intubation attempts, intubation conditions and post-operative
      hoarseness. RESULTS: Thirty-three patients were assessed for eligibility, and 25
      patients were included in the study with a median SARI score of 3 (IQR 3-4).
      Twenty-two (88%, 95% confidence interval [74-100%]) of the patients were
      successfully intubated by the method with a median time to intubation of 115 s
      (IQR 78-247). Steering and advancement of the tube were reported as acceptable in
      21 (84%) and 22 cases (88%), respectively, and excellent in 10 cases (45%) for
      both measures. Ten cases (40%) were intubated on the first attempt. There were
      three cases (12%) of failed intubation; in these cases, successful intubation was
      obtained by using a styletted tube. CONCLUSION(S): Most patients with anticipated
      difficult intubation can be successfully intubated with Boedeker intubation
      forceps and MVL. However, endotracheal tube placement failed in 3/25 patients
      despite a good laryngeal view.

PMID- 25982221
TI  - Brain processing of a configural vs elemental odor mixture in the newborn rabbit.
AB  - Organisms are surrounded throughout life by chemically complex odors. How
      individuals process an odorant within a mixture or a mixture as a whole is a key
      question in neuroethology and chemical senses. This question is addressed here by
      using newborn rabbits, which can be rapidly conditioned to a new stimulus by
      single association with the mammary pheromone. After conditioning to ethyl maltol
      (odorant B), pups behaviorally respond to B and an A'B' mixture (68/32 ratio) but
      not to ethyl isobutyrate (odorant A) or an AB mixture (30/70 ratio). This
      suggests elemental and configural perception of A'B' and AB, respectively. We
      then explored the neural substrates underlying the processing of these mixtures
      with the hypothesis that processing varies according to perception. Pups were
      pseudoconditioned or conditioned to B on postnatal day 3 before exposure to B,
      A'B' or AB on day 4. Fos expression was not similar between groups (mainly in the
      olfactory bulb and posterior piriform cortex) suggesting a differential
      processing of the stimuli that might reflect either stimulus complexity or
      conditioning effect. Thus, the ratio of components in A'B' vs AB leads to
      differential activation of the olfactory system which may contribute to elemental
      and configural percepts of these mixtures. In addition, together with recent
      behavioral data, this highlights that configural perception occurs even in
      relatively immature animals, emphasizing the value of the newborn rabbit for
      exploration of odor mixture processing from molecules to brain and behavior.

PMID- 25982224
TI  - Does food and fluid texture consumption relate to dietary intake in preschool
      children with cerebral palsy?

PMID- 25982223
TI  - Cross-cultural adaptation and validation of the Japanese version of the new Knee
      Society Scoring System for osteoarthritic knee with total knee arthroplasty.
AB  - BACKGROUND: The purposes of this study were to translate the new Knee Society
      Score (KSS) into Japanese and to evaluate the construct and content validity,
      test-retest reliability, and internal consistency of the Japanese version of the
      new KSS. METHODS: The Japanese version of the KSS was developed according to
      cross-cultural guidelines by using the "translation-back translation" method to
      ensure content validity. KSS data were then obtained from patients who had
      undergone total knee arthroplasty (TKA). The psychometric properties evaluated
      were as follows: for feasibility, response rate, and floor and ceiling effects;
      for construct validity, internal consistency using Cronbach's alpha, and
      correlations with quality of life. Construct validity was evaluated by using
      Spearman's correlation coefficient to quantify the correlation between the KSS
      and the Japanese version of the Oxford 12-item Knee Score or Short Form 36 Health
      Survey (SF-36) questionnaires. RESULTS: The Japanese version of the KSS was sent
      to 93 consecutive osteoarthritic patients who underwent primary TKA in our
      institution. Fifty-five patients completed the questionnaires and were included
      in this study. Neither a floor nor ceiling effect was observed. The reliability
      proved excellent in the majority of domains, with intraclass correlation
      coefficients of 0.65-0.88. Internal consistency, assessed by Cronbach's alpha,
      was good to excellent for all domains (0.78-0.94). All of the four domains of the
      KSS correlated significantly with the Oxford 12-item Knee Score. The activity and
      satisfaction domains of the KSS correlated significantly with all and the
      majority of subscales of the SF-36, respectively, whereas symptoms and
      expectation domains showed significant correlations only with bodily pain and
      vitality subscales and with the physical function, bodily pain, and vitality
      subscales, respectively. CONCLUSIONS: The Japanese version of the new KSS is a
      valid, reliable, and responsive instrument to capture subjective aspects of the
      functional symptoms and abilities of patients who undergo TKA.

PMID- 25982222
TI  - Multimodal connectivity mapping of the human left anterior and posterior lateral
      prefrontal cortex.
AB  - Working memory is essential for many of our distinctly human abilities, including
      reasoning, problem solving, and planning. Research spanning many decades has
      helped to refine our understanding of this high-level function as comprising
      several hierarchically organized components, some which maintain information in
      the conscious mind, and others which manipulate and reorganize this information
      in useful ways. In the neocortex, these processes are likely implemented by a
      distributed frontoparietal network, with more posterior regions serving to
      maintain volatile information, and more anterior regions subserving the
      manipulation of this information. Recent meta-analytic findings have identified
      the anterior lateral prefrontal cortex, in particular, as being generally engaged
      by working memory tasks, while the posterior lateral prefrontal cortex was more
      strongly associated with the cognitive load required by these tasks. These
      findings suggest specific roles for these regions in the cognitive control
      processes underlying working memory. To further characterize these regions, we
      applied three distinct seed-based methods for determining cortical connectivity.
      Specifically, we employed meta-analytic connectivity mapping across task-based
      fMRI experiments, resting-state BOLD correlations, and VBM-based structural
      covariance. We found a frontoparietal pattern of convergence which strongly
      resembled the working memory networks identified in previous research. A contrast
      between anterior and posterior parts of the lateral prefrontal cortex revealed
      distinct connectivity patterns consistent with the idea of a hierarchical
      organization of frontoparietal networks. Moreover, we found a distributed network
      that was anticorrelated with the anterior seed region, which included most of the
      default mode network and a subcomponent related to social and emotional
      processing. These findings fit well with the internal attention model of working
      memory, in which representation of information is processed according to an
      anteroposterior gradient of abstract-to-concrete representations.

PMID- 25982225
TI  - Role of hydration in phosphatidylcholine reverse micelle structure and gelation
      in cyclohexane: a molecular dynamics study.
AB  - In this work, we employ all-atom molecular dynamics simulations to examine the
      hydration response of phospholipid reverse micelles in cyclohexane. This ternary
      phospholipid-water-cyclohexane system is an important organogel forming system
      and the focus of this study is on gaining insight on the factors governing the
      gelation transition. We map the contributions rising from specific lipid-lipid
      and lipid-water interactions, and their response to increasing aggregate size and
      changes in water-to-lipid ratio. We find that, opposed to phospholipid-heptane
      organogels, in cyclohexane, lipid bridging and hydrogen bond driven stabilization
      of the lipid head group packing is at minor role in dictating the reverse micelle
      structural transitions corresponding to the organosol-organogel phase transition
      in this system. Instead, increasing the lipid head hydration changes the lipid
      packing factor directly which leads to gelation through the formation of long,
      wormlike micelles. Furthermore, the confined environment in the reverse micellar
      cores slows down the water dynamics significantly in comparison to fully hydrated
      phospholipid bilayers and at low water-to-lipid ratios this slow-down is even
      more significant. The findings map the role of hydration at microscopic level in
      these systems and could enable tailoring reverse micellar systems for
      applications relying on the structure and dynamics of the reverse micelles.
      Examples include such as drug transport, nanotemplating, or confined chemistry in
      the reverse micelle core water space, e.g., in catalysis. 

PMID- 25982226
TI  - [Health-related quality of life evaluation of elderly aged 65 years and over
      living at home].
AB  - BACKGROUND: To assess health-related quality of life in French adults aged 65
      years and over, living at home, with a specific self-administered questionnaire,
      the LEIPAD, cross-culturally adapted in French. METHODS: Elderly completed socio
      demographic and medical questionnaires, a questionnaire about negative life
      events during the last 12 months and the LEIPAD. RESULTS: Data of 195 subjects
      (mean age: 72.6 years, men: 56.5%) were analyzed. The response rates to the
      LEIPAD scales were superior to 90%. Elderly reported on the whole a good health
      related quality of life. Age had a negative effect on quality on life, which
      deteriorates over years. Age was correlated to the scales "Physical function",
      "Self-care", "Cognitive functioning" and "Sexual functioning". Elderly
      hospitalized in the last year had worse quality of life with a significant
      difference for "Physical function" scale. The number of health problems was
      positively correlated to "Physical function" scale. Elderly declaring at least
      one health problem had worse quality of life for this scale. Problems in couple,
      materials and financial problems had also negative effects on health-related
      quality of life. CONCLUSION: Our study highlights a good health-related quality
      of life for the majority of these adults aged 65 years and over, as well as the
      negative effect of age, health, couple, materials and financial problems on their
      quality of life.

PMID- 25982227
TI  - Improvement of the immune efficacy of carbohydrate vaccines by chemical
      modification on the GM3 antigen.
AB  - Tumor cells often display aberrant levels and patterns of cell surface
      glycosylation, which provides a potential opportunity to develop carbohydrate
      based anticancer vaccines for cancer immunotherapy. However, one of the most
      addressed challenges in this field is the low efficiency of the carbohydrate
      vaccination due to poor immunogenicity of carbohydrate antigens. In this article,
      a number of structure-modified GM3 antigen analogues were designed and chemically
      synthesized. The modified GM3 antigens were conjugated to protein carriers for
      vaccination. The vaccination results on mice show that the modification on the
      GM3 antigen could improve the efficiency of the vaccination, and in particular,
      two glycoconjugates (3-KLH and 8-KLH) elicited higher titers of anti-GM3
      antibodies than the unmodified GM3-protein conjugate (2-KLH) did.

PMID- 25982228
TI  - Multicolor Fluorescence Writing Based on Host-Guest Interactions and Force
      Induced Fluorescence-Color Memory.
AB  - A new strategy is reported for multicolor fluorescence writing on thin solid
      films with mechanical forces. This concept is illustrated by the use of a green
      fluorescent pentiptycene derivative 1, which forms variably colored fluorescent
      exciplexes: a change from yellow to red was observed with anilines, and
      fluorescence quenching (a change to black) occurred in the presence of
      benzoquinone. Mechanical forces, such as grinding and shearing, induced a
      crystalline-to-amorphous phase transition in both the pristine and guest-adsorbed
      solids that led to a change in the fluorescence color (mechanofluorochromism) and
      a memory of the resulting color. Fluorescence drawings of five or more colors
      were created on glass or paper and could be readily erased by exposure to air and
      dichloromethane fumes. The structural and mechanistic aspects of the observations
      are also discussed. 

PMID- 25982229
TI  - Fractal Nature of Metallic and Insulating Domain Configurations in a VO2 Thin
      Film Revealed by Kelvin Probe Force Microscopy.
AB  - We investigated the surface work function (WS) and its spatial distribution for
      epitaxial VO2/TiO2 thin films using Kelvin probe force microscopy (KPFM). Nearly
      grain-boundary-free samples allowed observation of metallic and insulating
      domains with distinct WS values, throughout the metal-insulator transition. The
      metallic fraction, estimated from WS maps, describes the evolution of the
      resistance based on a two-dimensional percolation model. The KPFM measurements
      also revealed the fractal nature of the domain configuration. 

PMID- 25982230
TI  - Solar Urticaria.

PMID- 25982231
TI  - A Comprehensive Approach to Tobacco Dependence Interventions.
AB  - Tobacco smoking remains the leading preventable cause of death and illness in the
      United States. Smoking cessation is particularly relevant for individuals with
      chronic obstructive pulmonary disease because it is known from multiple studies
      that individuals who quit smoking experience an initial improvement in pulmonary
      function, a decreased rate of normal age-related decline in FEV1, a lower risk of
      hospital admission, and improved survival. Tobacco dependence must be recognized
      as a chronic disease, and comprehensive treatment for the tobacco-dependent
      patient with chronic obstructive pulmonary disease begins with a physician's
      inquiry into smoking and encouragement to quit, followed by an assessment of the
      level of dependence and the severity of withdrawal symptoms during previous quit
      attempts. Combination pharmacotherapy is recommended for the initial treatment of
      most smokers, especially those with moderate to high baseline levels of tobacco
      dependence. The patient's history, combined with his or her personal preference,
      can guide the clinician in initiating an appropriate treatment regimen. Given the
      chronic nature of tobacco dependence, clinicians must anticipate relapses and the
      need for recurrent, long-term follow-up. Comprehensive tobacco treatment
      consultation should be sought whenever possible for patients with high levels of
      tobacco dependence and multiple relapses or failed quit attempts. 

PMID- 25982232
TI  - Proton microbeam radiotherapy with scanned pencil-beams--Monte Carlo simulations.
AB  - Irradiation, delivered by a synchrotron facility, using a set of highly
      collimated, narrow and parallel photon beams spaced by 1 mm or less, has been
      termed Microbeam Radiation Therapy (MRT). The tolerance of healthy tissue after
      MRT was found to be better than after standard broad X-ray beams, together with a
      more pronounced response of malignant tissue. The microbeam spacing and
      transverse peak-to-valley dose ratio (PVDR) are considered to be relevant
      biological MRT parameters. We investigated the MRT concept for proton microbeams,
      where we expected different depth-dose profiles and PVDR dependences, resulting
      in skin sparing and homogeneous dose distributions at larger beam depths, due to
      differences between interactions of proton and photon beams in tissue. Using the
      FLUKA Monte Carlo code we simulated PVDR distributions for differently spaced 0.1
      mm (sigma) pencil-beams of entrance energies 60, 80, 100 and 120 MeV irradiating
      a cylindrical water phantom with and without a bone layer, representing human
      head. We calculated PVDR distributions and evaluated uniformity of target
      irradiation at distal beam ranges of 60-120 MeV microbeams. We also calculated
      PVDR distributions for a 60 MeV spread-out Bragg peak microbeam configuration.
      Application of optimised proton MRT in terms of spot size, pencil-beam
      distribution, entrance beam energy, multiport irradiation, combined with relevant
      radiobiological investigations, could pave the way for hypofractionation
      scenarios where tissue sparing at the entrance, better malignant tissue response
      and better dose conformity of target volume irradiation could be achieved,
      compared with present proton beam radiotherapy configurations.

PMID- 25982233
TI  - Using molecular biomarkers and traditional morphometric measurements to assess
      the health of slimy sculpin (Cottus cognatus) from streams with elevated selenium
      in North-Eastern British Columbia.
AB  - Canadian fish-based environmental effects monitoring programs use individual and
      population-level endpoints to assess aquatic health. Impacts of coal mining and
      selenium (Se) exposure were assessed in slimy sculpin (Cottus cognatus) from
      reference streams located both inside and outside of a coal zone, and from 1
      stream with a history of coal mining, using traditional environmental effects
      monitoring endpoints. In addition, physical characteristics of the streams and
      benthic macro-invertebrate communities were assessed. To determine whether the
      assessment of effects could be improved by including molecular markers, real-time
      polymerase chain reaction assays were optimized for genes associated with
      reproduction (vtg, esr1, star, cyp19a1, and gys2), and oxidative and cellular
      stress (sod1, gpx, gsr, cat, and hsp 90). Water Se levels exceeded guidelines in
      the stream with historical mining (4 MUg/L), but benthic macroinvertebrates did
      not exceed dietary thresholds (2-3 MUg/g dry wt). Whole-body Se levels were above
      British Columbia's tissue guideline in fish from all streams, but only above the
      draft US Environmental Protection Agency (USEPA) criterion (7.91 MUg/g dry wt) at
      the reference stream inside the coal zone. Some markers of cellular and oxidative
      stress were elevated in fish liver at the exposed site (sod1, gpx), but some were
      lower (cat, sod1, gpx, gsr, hsp90) in the gonads of fish inside the coal zone.
      Some of the differences in gene expression levels between the reference and
      impacted sites were sex dependent. Based on benthic macroinvertebrate
      assessments, the authors hypothesize that traditional and molecular differences
      in slimy sculpin at impacted sites may be driven by food availability rather than
      Se exposure. The present study is the first to adapt molecular endpoints in the
      slimy sculpin for aquatic health assessments.

PMID- 25982234
TI  - Parenteral nutrition-associated liver disease and lipid emulsions.
AB  - Parenteral nutrition-associated liver disease (PNALD) is a particularly important
      problem in patients who need this type of nutritional support for a long time.
      Prevalence of the condition is highly variable depending on the series, and its
      clinical presentation is different in adults and children. The etiology of PNALD
      is not well defined, and participation of several factors at the same time has
      been suggested. When a bilirubin level >2 mg/dl is detected for a long time,
      other causes of liver disease should be ruled out and risk factors should be
      minimized. The composition of lipid emulsions used in parenteral nutrition is one
      of the factors related to PNALD. This article reviews the different types of
      lipid emulsions and the potential benefits of emulsions enriched with omega-3
      fatty acids.

PMID- 25982235
TI  - Effects of knee position on blood loss following total knee arthroplasty: a
      randomized, controlled study.
AB  - OBJECTIVE: Blood loss following total knee arthroplasty is a serious side-effect
      of surgery and impacts on patient recovery and quality of life. The aim of this
      study was to assess the effect of postoperative knee position during recovery on
      blood loss and range of motion. METHODS: One hundred consecutive patients, with
      stage III or IV degenerative osteoarthritis, were enrolled in the study and
      randomized equally between two treatment groups: flexion and extension. In the
      flexion group, the affected leg was elevated postoperatively by 45 degrees  at
      the hip, with 45 degrees  flexion at the knee, while patients in the extension
      group had the knee extended fully. Blood loss, pre- and postoperative hemoglobin
      levels, and range of motion were recorded together with duration of hospital stay
      and complications. RESULTS: Calculated blood loss, hidden blood loss, and
      postoperative hemoglobin levels between the two groups were significantly
      different, with patients in the flexion group experiencing lower blood loss than
      those in the extension group (P < 0.05). After 6-week rehabilitation, patients
      from both groups attained a similar range of motion in the joint. Duration of
      hospital stay was shorter in the flexion group by 1.6 days. Wound infection rates
      were similar in both groups, and we observed no proven deep vein thrombosis.
      CONCLUSIONS: Postoperative elevation of the hip by 45 degrees , with 45 degrees 
      knee flexion, is an effective and simple method of reducing blood loss and
      hospital stay following unilateral primary total knee arthroplasty.

PMID- 25982236
TI  - Oral Rehydration Therapy and Feeding Replaces Total Parenteral Nutrition: A
      Clinical Vignette.
AB  - A 27-year-old patient with spina bifida and a high output loss of water and
      electrolytes from her ileostomy was successfully liberated from dependency on
      total parenteral nutrition and intravenous fluid and electrolyte replacement by
      the use of a rice-based oral rehydration therapy (ORT). This allowed her to
      return home to the care of her mother. We suggest that ORT can be effective in
      the context of modern high-technology settings, as well as in resource-poor
      situations. 

PMID- 25982237
TI  - Capsule Commentary on Aysola et al., Asking the Patient About Patient-Centered
      Medical Homes: A Qualitative Analysis.

PMID- 25982238
TI  - Lymph node grafting in the treatment of upper limb lymphoedema: a clinical trial.
AB  - BACKGROUND: Microvascular lymph node transfer has been shown to improve the
      severity of lymphoedema. However, microvascular surgery is not suitable for all
      patients. Simple lymph node grafting does not require general anaesthetic or
      significant surgical resources and is a technique that has been tested in animal
      models only until this point. Our hypothesis is that the transplanted lymph nodes
      integrate into the lymphovascular system and function as a 'pump', directly
      pumping interstitial fluid back into the venous system. METHODS: We hypothesized
      that lymph node grafting would improve lymphoedema with a low risk of
      complications. The procedure was performed in a day surgery setting under local
      anaesthetic with sedation. Two lymph nodes were harvested from the groin and
      grafted into subcutaneous tissue on the volar aspect of the affected limb at
      supratrochlear and wrist levels. RESULTS: We found that nine of 10 patients
      reported a subjective and/or functional improvement in their lymphoedema,
      including an improvement in hand function and tissue feel. Truncal cone
      calculation volumes showed an overall decrease in affected limb volume of 89.7 mL
      (standard deviation = 136.5). Furthermore, follow-up lymphoscintigram imaging on
      one patient demonstrated viability and function of the implanted node.
      CONCLUSIONS: We conclude that this is a safe procedure and should be further
      investigated as an alternative to a microsurgical procedure as a treatment for
      upper limb lymphoedema. Further research with a larger sample size is needed to
      confirm the findings of this pilot study.

PMID- 25982239
TI  - The Platelet Function Analyser (PFA)-100 and von Willebrand disease: a story well
      over 16 years in the making.

PMID- 25982240
TI  - Impact of Injection-Guiding Techniques on the Effectiveness of Botulinum Toxin
      for the Treatment of Focal Spasticity and Dystonia: A Systematic Review.
AB  - OBJECTIVE: To conduct a systematic review of the impact of different injection
      guiding techniques on the effectiveness of botulinum toxin type A (BoNT-A) for
      the treatment of focal spasticity and dystonia. DATA SOURCES: MEDLINE via PubMed,
      Academic Search Premier, PASCAL, The Cochrane Library, Scopus, SpringerLink, Web
      of Science, EM Premium, and PsycINFO. STUDY SELECTION: Two reviewers
      independently selected studies based on predetermined inclusion criteria. DATA
      EXTRACTION: Data relating to the aim were extracted. Methodological quality was
      graded independently by 2 reviewers using the Physiotherapy Evidence Database
      assessment scale for randomized controlled trials (RCTs) and the Downs and Black
      evaluation tool for non-RCTs. Level of evidence was determined using the modified
      Sackett scale. DATA SYNTHESIS: Ten studies were included. Seven were randomized.
      There was strong evidence (level 1) that instrumented guiding (ultrasonography
      [US], electrical stimulation [ES], electromyogram [EMG]) was more effective than
      manual needle placement for the treatment of spasmodic torticollis, upper limb
      spasticity, and spastic equinus in patients with stroke, and spastic equinus in
      children with cerebral palsy. Three studies provided strong evidence (level 1) of
      similar effectiveness of US and ES for upper and lower limb spasticity in
      patients with stroke, and spastic equinus in children with cerebral palsy, but
      there was poor evidence or no available evidence for EMG or other instrumented
      techniques. CONCLUSIONS: These results strongly recommend instrumented guidance
      of BoNT-A injection for the treatment of spasticity in adults and children (ES or
      US), and of focal dystonia such as spasmodic torticollis (EMG). No specific
      recommendations can be made regarding the choice of instrumented guiding
      technique, except that US appears to be more effective than ES for spastic
      equinus in adults with stroke.

PMID- 25982241
TI  - A comparative computationally study about the defined M(II) pincer hydrogenation
      catalysts (M = Fe, Ru, Os).
AB  - The mechanism of acetonitrile and methyl benzoate catalytic hydrogenation using
      pincer catalysts M(H)2 (CO)[NH(C2 H4 PiPr2 )2 ] (1M) and M(H)(CO)[N(C2 H4 PiPr2
      )2 ] (2M) (M = Fe, Ru, Os) has been computed at various levels of density
      functional theory. The computed equilibrium between 1Fe and 2Fe agrees perfectly
      with the experimental observations. On the basis of the activation barriers and
      reaction energies, the best catalysts for acetonitrile hydrogenation are 1Fe/2Fe
      and 1Ru/2Ru, and the best catalysts for methyl benzoate hydrogenation are
      1Ru/2Ru. The best catalysts for the dehydrogenation of benzyl alcohol are
      1Ru/2Ru. It is to note that the current polarizable continuum model is not
      sufficient in modeling the solvation effect in the energetic properties of these
      catalysts as well as their catalytic properties in hydrogenation reaction, as no
      equilibrium could be established between 1Fe and 2Fe. Comparison with other
      methods and procedures has been made. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25982242
TI  - Contact-free physiological monitoring using a markerless optical system.
AB  - PURPOSE: Physiological noise remains a major problem in MRI, particularly at
      higher imaging resolutions and field strengths. The aim of this work was to
      investigate the feasibility of using an MR-compatible in-bore camera system to
      perform contactless monitoring of cardiac and respiratory information during MRI
      of human subjects. METHODS: An MR-compatible camera was mounted on an eight
      channel head coil. Video data of the skin was processed offline to derive cardiac
      and respiratory signals from the pixel signal intensity and from head motion in
      the patient head-feet direction. These signals were then compared with data
      acquired simultaneously from the pulse oximeter and the respiratory belt.
      RESULTS: The cardiac signal computed using the average image pixel intensity
      closely resembled the signal obtained using the pulse oximeter. Trigger intervals
      obtained from both systems matched to within 50 ms (one standard deviation). The
      respiratory signal computed from small in-plane movements closely matched the
      signal obtained from the respiratory belt. Simultaneous MR imaging did not appear
      to have an effect on the physiological signals acquired by means of the contact
      free monitoring system. CONCLUSION: Contact-free monitoring of human subjects to
      obtain cardiac and respiratory information is feasible using a small camera and
      light emitting diode mounted on the head coil of an MRI scanner.

PMID- 25982243
TI  - Prolidase-dependent mechanism of (Z)-8,9-epoxyheptadeca-1,11,14-triene-induced
      inhibition of collagen biosynthesis in cultured human skin fibroblasts.
AB  - The effects of polyolefinic compound from roots of Cirsium palustre, (Z)-8,9
      epoxyheptadeca-1,11,14-triene (EHT) on collagen biosynthesis, prolidase activity,
      expression of insulin-like growth factor receptor (IGF-IR), beta1 integrin, MAP
      kinases (pERK1/2), the transcription factors such as nuclear factor kappa B (NF
      kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha) were evaluated in human
      dermal fibroblasts treated with micromolar concentrations (40-200 MUM) for 24 h.
      It was found that EHT-dependent inhibition of collagen biosynthesis was
      accompanied by parallel inhibition in prolidase activity. Since IGF-I is the most
      potent regulator of both processes and prolidase is regulated by beta1 integrin
      signalling, the effect of EHT on IGF-IR and beta1 integrin receptor expressions
      were evaluated. Exposure of the cells to EHT contributed to distinct increase in
      IGF-IR and slight increase in beta1 integrin receptor expressions. It was
      accompanied by decrease in expression of pERK1/2, HIF-1alpha and NF-kappaB. EHT
      dependent inhibition of collagen biosynthesis results from inhibition of
      prolidase activity, the enzyme involved in collagen biosynthesis.

PMID- 25982244
TI  - Use of procalcitonin, C-reactive protein and white blood cell count to
      distinguish between lower limb erysipelas and deep vein thrombosis in the
      emergency department: A prospective observational study.
AB  - Early differentiation of erysipelas from deep vein thrombosis (DVT) based solely
      on clinical signs and symptoms is challenging. There is a lack of data regarding
      the usefulness of the inflammatory biomarkers procalcitonin (PCT), C-reactive
      protein (CRP) and white blood cell (WBC) count in the diagnosis of localized
      cutaneous infections. Herein, we investigated the diagnostic value of
      inflammatory markers in a prospective at-risk patient population. This is an
      observational quality control study including consecutive patients presenting
      with a final diagnosis of either erysipelas or DVT. The association of PCT
      (MUg/L) and CRP (mg/L) levels and WBC counts (g/L) with the primary outcome was
      assessed using logistic regression models with area under the receiver-operator
      curve. Forty-eight patients (erysipelas, n = 31; DVT, n = 17) were included.
      Compared with patients with DVT, those with erysipelas had significantly higher
      PCT concentrations. No significant differences in CRP concentrations and WBC
      counts were found between the two groups. At a PCT threshold of 0.1 MUg/L or
      more, specificity and positive predictive values (PPV) for erysipelas were 82.4%
      and 85.7%, respectively, and increased to 100% and 100% at a threshold of more
      than 0.25 MUg/L. Levels of PCT also correlated with the severity of erysipelas,
      with a stepwise increase according to systemic inflammatory response syndrome
      criteria. We found a high discriminatory value of PCT for differentiation between
      erysipelas and DVT, in contrast to other commonly used inflammatory biomarkers.
      Whether the use of PCT levels for early differentiation of erysipelas from DVT
      reduces unnecessary antibiotic exposure needs to be assessed in an interventional
      trial. 

PMID- 25982246
TI  - The role of primary tumor resection in neuroblastoma: When and how much?

PMID- 25982245
TI  - Peptide-based inhibition of IkappaB kinase/nuclear factor-kappaB pathway protects
      against diabetes-associated nephropathy and atherosclerosis in a mouse model of
      type 1 diabetes.
AB  - AIMS/HYPOTHESIS: The canonical nuclear factor-kappaB (NF-kappaB) pathway mediated
      by the inhibitor of NF-kappaB kinase (IKK) regulates the transcription of
      inflammatory genes involved in the pathogenesis of diabetes, from the early phase
      to progression and final complications. The NF-kappaB essential modulator binding
      domain (NBD) contained in IKKalpha/beta is essential for IKK complex assembly. We
      therefore investigated the functional consequences of targeting the IKK-dependent
      NF-kappaB pathway in the progression of diabetes-associated nephropathy and
      atherosclerosis. METHODS: Apolipoprotein E-deficient mice with diabetes induced
      by streptozotocin were treated with a cell-permeable peptide derived from the
      IKKalpha/beta NBD region. Kidneys and aorta were analysed for morphology,
      leucocyte infiltrate, collagen, NF-kappaB activity and gene expression. In vitro
      studies were performed in renal and vascular cells. RESULTS: NBD peptide
      administration did not affect the metabolic severity of diabetes but resulted in
      renal protection, as evidenced by dose-dependent decreases in albuminuria, renal
      lesions (mesangial expansion, leucocyte infiltration and fibrosis), intranuclear
      NF-kappaB activity and proinflammatory and pro-fibrotic gene expression.
      Furthermore, peptide treatment limited atheroma plaque formation in diabetic mice
      by decreasing the content of lipids, leucocytes and cytokines and increasing
      plaque stability markers. This nephroprotective and anti-atherosclerotic effect
      was accompanied by a decline in systemic T helper 1 cytokines. In vitro, NBD
      peptide prevented IKK assembly/activation, p65 nuclear translocation, NF-kappaB
      regulated gene expression and cell proliferation induced by either high glucose
      or inflammatory stimulation. CONCLUSIONS/INTERPRETATION: Peptide-based inhibition
      of IKK complex formation attenuates NF-kappaB activation, suppresses inflammation
      and retards the progression of renal and vascular injury in diabetic mice, thus
      providing a feasible approach against diabetes inflammatory complications.

PMID- 25982247
TI  - Ayurvedic doshas as predictors of sleep quality.
AB  - BACKGROUND: The 3 Ayurvedic constitutional types or Doshas--vata, pitta, and
      kapha--are responsible for homeostasis and health. The doshas determine various
      functions, including sleep. According to the Ayurvedic texts, sleep is caused by
      increased kapha and insomnia by increased vata or pitta, which may follow
      physical or mental exertion, or disease. The present study was carried out to
      determine whether this relationship could be found using contemporary
      standardized questionnaires. MATERIAL/METHODS: In this cross-sectional single
      group study, 995 persons participated (646 males; group average age +/-S.D.,
      49.1+/-15.2 years). Participants were attending a 1-week residential yoga program
      in northern India. Participants were assessed for dosha scores using a Tridosha
      questionnaire and the quality of sleep in the preceding week was self-rated using
      a sleep rating questionnaire. RESULTS: Multiple linear regression analyses were
      used to determine if each dosha acted as a predictor of quality and quantity of
      sleep. Vata scores significantly predicted the time taken to fall asleep
      [p<0.01], and the feeling of being rested in the morning [p<0.001]; with higher
      vata scores being associated with a longer time to fall asleep and a lesser
      feeling of being rested in the morning. Kapha scores significantly predicted day
      time somnolence [p<0.05] and the duration of day-time naps in minutes [p<0.05],
      with higher kapha scores being associated with longer day-time naps. CONCLUSIONS:
      The results suggest that the doshas can influence the quality and quantity of
      sleep.

PMID- 25982248
TI  - Expression, purification and immobilization of recombinant AiiA enzyme onto
      magnetic nanoparticles.
AB  - AiiA is a "28-kDa lactonase" from Gram-positive Bacillus sp. 240B1. The enzyme
      can hydrolyze and inactivate a variety of acyl homoserine lactones (AHLs), quorum
      sensor molecules involve in bacterial quorum sensing (QS). AiiA is a strong
      candidate for the development of bio-decontaminating agent that can disrupt QS in
      industrial and environmental samples. However, commercial application of AiiA
      suffer from several limitations including high cost of production of enzyme and
      lack of efficient recovery mean(s) of enzyme from the application environment for
      its reuse. In this study we have cloned, expressed and purified recombinant AiiA
      (r-AiiA) enzyme. The purified enzyme was covalently immobilized onto magnetic
      nanoparticles (MNPs) and the quorum quenching ability of r-AiiA-MNP
      nanobiocatalyst was evaluated in aqueous buffer. Our results show that r-AiiA
      MNPs (a) can hydrolyze 3O-C10AHL and inhibit QS in aqueous buffer, (b) can be
      recovered from the reaction mixture using external magnetic field, and (c) can be
      reused multiple times to hydrolyze 3O-C10AHL in aqueous buffer. Results of this
      study can be used to develop a formulation of AiiA enzyme for industrial
      applications. 

PMID- 25982249
TI  - Assessment of Biventricular Function by Three-Dimensional Speckle-Tracking
      Echocardiography in Secondary Mitral Regurgitation after Repair with the
      MitraClip System.
AB  - BACKGROUND: The goal of this study was to determine changes in left ventricular
      (LV) and right ventricular (RV) function with three-dimensional (3D) speckle
      tracking echocardiography (STE) after percutaneous mitral valve repair with the
      MitraClip system in high-risk surgical patients with moderate to severe or severe
      secondary mitral regurgitation (MR). METHODS: Thirty-two patients with MR
      undergoing MitraClip were prospectively included. Patients underwent two
      dimensional (2D) and 3D transthoracic echocardiography before clip implantation
      and after 6-month follow-up. LV and RV longitudinal strain was obtained by 2D STE
      and 3D STE. LV circumferential, radial, and area strain was calculated by 3D STE.
      Data analysis was performed offline. RESULTS: At 6-month follow-up, significant
      improvements were seen in LV 2D global longitudinal strain (P < .005), 3D global
      longitudinal strain (P = .0002), and 3D area strain (P = .0001). Overall,
      significant improvements were also seen in 3D RV ejection fraction (P < .05) and
      3D RV free-wall longitudinal strain (P < .05). A poor increase in LV strain after
      clip implantation (P = NS) occurred in patients with pronounced preexisting RV
      dysfunction. The areas under the receiver operating characteristic curves for LV
      and RV 3D speckle-tracking echocardiographic parameters showed high
      discriminative values (range, 0.87-0.91) in predicting unfavorable outcomes with
      persistent symptoms (New York Heart Association class > II) after the procedure.
      CONCLUSIONS: Three-dimensional STE showed overall LV and RV strain improvement
      after clip implantation as well as lower postprocedural LV strain values in
      patients with worse preexisting RV function. These findings could help in guiding
      MR treatment strategies, suggesting different therapies in the presence of marked
      RV impairment or anticipating the procedure in case of evolving RV dysfunction.

PMID- 25982250
TI  - Modulation of mgrB gene expression as a source of colistin resistance in
      Klebsiella oxytoca.
AB  - Gene modifications in the PmrAB and PhoPQ two-component regulatory systems, as
      well as inactivation of the mgrB gene, are known to be causes of colistin
      resistance in Klebsiella pneumoniae. The objective of this study was to
      characterise the mechanism involved in colistin resistance in a Klebsiella
      oxytoca isolate. A K. oxytoca clinical isolate showing resistance to colistin was
      recovered in Cali, Colombia. The pmrA, pmrB, phoP, phoQ and mgrB genes were
      amplified and sequenced. Wild-type mgrB genes from K. pneumoniae and K. oxytoca
      were cloned, and corresponding recombinant plasmids were used for complementation
      assays. By analysing the mgrB gene of the K. oxytoca isolate and its flanking
      sequences, an insertion sequence (IS) of 1196bp was identified in its promoter
      region. The insertion was located between nucleotides -39 and -38 when referring
      to the start codon of the mgrB gene, thus negatively interfering with expression
      of the mgrB gene by modifying its promoter structure. This IS was very similar to
      ISKpn26 (99% nucleotide identity) belonging to the IS5 family. Complementation
      assays with mgrB genes from wild-type K. pneumoniae or K. oxytoca restored full
      susceptibility to colistin. In conclusion, here we identified the mechanism
      involved in colistin resistance in a K. oxytoca isolate. Modulation of mgrB gene
      expression was the key factor for this acquired resistance to colistin. 

PMID- 25982251
TI  - The pathogenesis of inflammation and cancer in the gastrointestinal tract: from
      basic science to translational medicine.

PMID- 25982252
TI  - Carbon fiber intramedullary nails reduce artifact in postoperative advanced
      imaging.
AB  - OBJECTIVE: This study assessed whether radiolucent carbon fiber reinforced
      polyetheretherketone (CFR-PEEK) intramedullary nails decreased hardware artifact
      on magnetic resonance imaging (MRI) and computed tomography (CT) in vitro and in
      an oncologic patient population. MATERIALS AND METHODS: In vitro and clinical
      evaluations were done. A qualitative assessment of metal artifact was performed
      using CFR-PEEK and titanium nail MRI phantoms. Eight patients with a femoral or
      tibial prophylactic CFR-PEEK nail were retrospectively identified. All patients
      had postoperative surveillance imaging by MRI, CT, and were followed for a median
      20 months (range, 12-28 months). CFR-PEEK images were compared to images from a
      comparative group of patients with titanium femoral intramedullary nails who had
      a postoperative MRI or CT. A musculoskeletal-trained radiologist graded
      visualization of the cortex, corticomedullary junction, and bone-muscle
      interface, on T1-weighted (T1W), STIR, and contrast-enhanced T1-weighted fat
      saturated (T1W FS) sequences of both groups with a five-point scale, performing
      independent reviews 4 months apart. Statistical analysis used the Wilcoxon rank
      sum test and a weighted kappa. RESULTS: Substantially less MRI signal loss
      occurred in the CFR-PEEK phantom than in the titanium phantom simulation,
      particularly as the angle increased with respect to direction of the static
      magnetic field. CFR-PEEK nails had less MRI artifact than titanium nails on
      scored T1W, STIR, and contrast-enhanced T1W FS MRI sequences (p <= 0.03). The
      mean weighted kappa was 0.64, showing excellent intraobserver reliability between
      readings. CONCLUSIONS: CFR-PEEK intramedullary nail fixation is a superior
      alternative to minimize implant artifact on MRI or CT imaging for patients
      requiring long bone fixation.

PMID- 25982253
TI  - An aggressive case of pseudomyogenic haemangioendothelioma of bone with
      pathological fracture and rapidly progressive pulmonary metastatic disease: case
      report and review of the literature.
AB  - Pseudomyogenic haemangioendothelioma (PMH) is a rare recently described vascular
      tumour typically presenting with soft tissue disease in distal extremities of
      young adults. Multi-focal and multi-layered involvement is commonly recognised.
      The majority of cases described so far have shown an indolent clinical course and
      distant metastatic spread is rare. We report a case of PMH in an 82-year-old male
      diagnosed following a pathological fracture of the distal tibia. Further bone
      lesions were identified in the fibula, patella and distal femur. The patient was
      found to have multiple nodules suspicious for pulmonary metastases on a CT scan
      at the time of diagnosis that showed significant progression at a follow-up scan
      4 weeks later. To our knowledge, this is the first reported case of PMH
      presenting with a pathological fracture. The rapid progression of bone and
      distant metastatic disease in this case is highly unusual given the typically
      indolent clinical course reported in the literature to date. 

PMID- 25982254
TI  - Depressive-like behavior induced by tumor necrosis factor-alpha is attenuated by
      m-trifluoromethyl-diphenyl diselenide in mice.
AB  - A growing body of evidence associates activation of immune system with depressive
      symptoms. Accordingly, pro-inflammatory cytokines, such as tumor necrosis factor
      alpha (TNF-alpha), have been shown to play a pivotal role in the pathophysiology
      of depression. The aim of this study was to evaluate the effectiveness of acute
      and subchronic treatments with (m-CF3-PhSe)2 to prevent the depressive-like
      behavior induced by intracerebroventricular injection of TNF-alpha in mice. TNF
      alpha induced depressive-like behavior in the forced swimming test (FST) and tail
      suspension test (TST) (0.1 and 0.001 fg/5 MUL/site, respectively) without
      changing locomotor activity, performed in the locomotor activity monitor (LAM).
      Acute (0.01-50 mg/kg; intragastric (i.g.); 30 min) and subchronic (0.01 and 0.1
      mg/kg; i.g.; 14 days) treatments with (m-CF3-PhSe)2 at low doses were effective
      against the effect of TNF-alpha in the FST and TST. Nuclear factor-kappaB (NF
      kappaB) and p38 mitogen-activated protein kinase (p38 MAPK), important proteins
      in TNF-activated signaling, were determined in the prefrontal cortex and
      hippocampus of mouse. TNF-alpha (0.1 fg/5 MUL/site) increased NF-kappaB levels
      and p38 MAPK activation in both brain areas and acute (10 mg/kg; i.g.) and
      subchronic (0.01 mg/kg; i.g.) treatments with (m-CF3-PhSe)2 were effective in
      attenuating this increase. Although more studies are necessary to indicate this
      compound as a therapeutic alternative to depression, the antidepressant-like and
      anti-inflammatory effects of (m-CF3-PhSe)2 demonstrated herein may support it as
      an interesting molecule in the search for new drugs to treat depressive disorders
      that have been largely linked to immune process and inflammation.

PMID- 25982255
TI  - Causes of Individual Differences in Animal Exploration and Search.
AB  - Numerous studies have documented individual differences in exploratory tendencies
      and other phenomena related to search, and these differences have been linked to
      fitness. Here, I discuss the origins of these differences, focusing on how
      experience shapes animal search and exploration. The origin of individual
      differences will also depend upon the alternatives to exploration that are
      available. Given that search and exploration frequently carry significant costs,
      we might expect individuals to utilize cues indicating the potential net payoffs
      of exploration versus the exploitation of known acts. Informative cues could
      arise from both recent and early-life experiences, from both the social and
      physical environment. Open questions are the extent to which an individual's
      exploratory tendencies are fixed throughout life versus being flexibly adjusted
      according to prevailing conditions and the actions of other individuals, and the
      extent to which individual differences in exploration extend across domains and
      are independent of other processes. 

PMID- 25982257
TI  - Latent Pathways Identification by Microarray Expression Profiles in Thyroid
      Associated Ophthalmopathy Patients.
AB  - This study aimed to screen potential genes related to thyroid-associated
      ophthalmopathy (TAO) and get a further understanding about the pathogenesis of
      this disease. GSE9340 was downloaded from Gene Expression Omnibus, including
      eight thyroid tissue samples from hyperthyroid patients without TAO and ten ones
      from hyperthyroid patients with TAO. The differentially expressed genes (DEGs)
      were identified by the linear models for microarray data package. And their
      potential functions were predicted by Gene Ontology (GO) and pathway enrichment
      analyses. Furthermore, protein-protein interaction (PPI) was obtained from the
      Search Tool for the Retrieval of Interacting Genes database, and the PPI network
      was visualized with Cytoscape. Then, module analysis was performed by the
      Molecular Complex Detection analysis. Additionally, the potential pathway
      interactions were identified by Latent Pathway Identification Analysis. Totally,
      511 upregulated and 507 downregulated DEGs in TAO were screened. Some DEGs (e.g.,
      UBE2C) were related to cell cycle, and DEGs encoding proteasome (e.g., PSMA1,
      PSMC5, PSMC4, and PSMD1) were related to negative regulation of ubiquitin-protein
      ligase activity. Several upregulated DEGs encoding signal recognition particle
      (e.g., SRP14, SRP54, and SRP9) were found to be enriched in protein export
      pathway. Furthermore, some pathways (e.g., ribosome and protein export) had
      interactions. The DEGs related to cell cycle (e.g., UBE2C), DEGs encoding
      proteasome (e.g., PSMA1, PSMC5, PSMC4, and PSMD1) and signal recognition particle
      (e.g., SRP14, SRP54, and SRP9), as well as pathways of ribosome, protein export
      and retinol metabolism, might play key roles in the development of TAO. 

PMID- 25982258
TI  - Cytological and Immunocytochemical Features of Merkel Cell Carcinoma on Fine
      Needle Cytology Samples: A Study of 22 Cases.
AB  - Merkel cell carcinoma (MCC) is an uncommon neuroendocrine small cell tumor
      derived from the transformation of the homonymous cells in the basal layer of the
      epidermis. MCC has a generally aggressive course, with a high tendency for local
      recurrence, lymph node involvement, and distant metastasis. Fine needle cytology
      (FNC) and immunocytochemistry were used as diagnostic procedures for 22 cases of
      MCC presented at our institute. All cases of MCC were successfully diagnosed on
      FNC. Among all of the monoclonal antisera used (CD56, CK20, CK MNF116, neuron
      specific enolase (NSE), synaptophysin, and chromogranin), NSE and CD56 showed the
      highest frequency of positivity. The accuracy of the cytological diagnosis was
      100% compared to the corresponding previous or subsequent pathological diagnoses.
      FNC and immunocytochemistry represent excellent and accurate diagnostic methods
      to distinguish MCC from other small-cell malignant entities.

PMID- 25982259
TI  - Acalculous cholecystitis associated with hemorrhagic fever with renal syndrome.
AB  - Hantaviruses are responsible for various types of hemorrhagic fevers depending on
      the involved subtype. In Europe, Puumala virus is responsible for an epidemic
      nephropathy. This infection can be complicated by severe abdominal pain. A rarely
      reported cause of this presenting symptom is acalculous cholecystitis, which must
      be integrated in the clinicobiological spectrum and should not lead to a surgical
      sanction. Its presence seems to be correlated with the severity of the disease,
      whose main pathophysiological phenomenon is plasma leakage induced by a
      microvascular endothelial dysfunction. We report the case of a young male patient
      who presented with severe hantavirus infection complicated by acalculous
      cholecystitis. 

PMID- 25982260
TI  - Association between microbiological and serological prevalence of human
      pathogenic Yersinia spp. in pigs and pig batches.
AB  - Pigs are the main reservoir of human pathogenic Y. enterocolitica, and the
      microbiological and serological prevalence of this pathogen differs between pig
      farms. The infection status of pig batches at moment of slaughter is unknown
      while it is a possibility to classify batches. A relation between the presence of
      human pathogenic Yersinia spp. and the presence of antibodies could help to
      predict the infection of the pigs prior to slaughter. Pigs from 100 different
      batches were sampled. Tonsils and pieces of diaphragm were collected from 7047
      pigs (on average 70 pigs per batch). The tonsils were analyzed using a direct
      plating method and the meat juice collected from the pieces of diaphragm was
      analyzed by Enzyme Linked ImmunoSorbent Assay. The microbiological and
      serological results were compared using a mixed-effects logistic regression at
      pig and batch level. Yersinia spp. were found in 2031 (28.8%) pigs, antibodies
      were present in 4692 (66.6%) pigs. According to the logistic regression, there
      was no relation at pig level between the presence of Yersinia spp. in tonsils and
      the presence of antibodies. Contrarily, at batch level, a mean activity value of
      37 Optical Density (OD)% indicated a Yersinia spp. positive farm and the
      microbiological prevalence in pig batches could be estimated before shipment to
      the slaughterhouse. This offers the opportunity to classify batches based on
      their potential risk to contaminate carcasses with human pathogenic Yersinia spp.

PMID- 25982261
TI  - Prevalence and characterization of Salmonella in pigs from conventional and
      organic farms and first report of S. serovar 1,4,[5],12:i:- from Korea.
AB  - This study compared the prevalence of Salmonella spp. and their antimicrobial
      susceptibilities in pigs from conventional and organic farms during 2012-2013 in
      Korea and characterized them by molecular methods. Altogether, 100 nontyphoid
      Salmonella were isolated: 47 from 1324 pigs (3.5%) from conventional farms and 53
      from 641 pigs (8.3%) from organic farms. The most frequent serovar was
      Typhimurium (49%) followed by Panama (24%), 1,4,[5],12:i:- (5%), and Virchow
      (5%). Overall, the isolates were most often resistant to tetracycline (75%)
      followed by ampicillin (66%), streptomycin (57%), and gentamicin (44%). The
      prevalence of antimicrobial resistance, multi-drug resistance phenotype, and
      resistance to tetracycline, ampicillin, and gentamicin were significantly higher
      in swine Salmonella from conventional farms than those from organic farms. The
      most common resistance pattern was ampicillin-gentamicin-tetracycline (n=16). All
      eight ceftiofur-resistant Salmonella identified produced CTX-M-15. Overall,
      decreased susceptibility to ciprofloxacin was observed in 39 isolates. Among
      them, a single isolate was positive for qnrS1 gene. An insertion sequence ISEcp1
      was detected upstream of blaCTX-M gene in all isolates. The spread of blaCTX-M-15
      gene was attributed to combination of clonal expansion and horizontal
      dissemination mediated by IncHI2 plasmid. Multilocus variable number of tandem
      repeats analysis demonstrated clonal dissemination of S. Typhimurium and S.
      1,4,[5],12:i:- strains in pigs. To our knowledge, this is the first report of
      blaCTX-M-15 gene in S. Virchow from pigs and qnrS1 gene in S. Rissen from
      animals. This study also reports the first occurrence of Salmonella serovar
      1,4,[5],12:i:- from Korea and CTX-M-15 producing Salmonella from pigs in Korea. 

PMID- 25982262
TI  - Administration of a maple syrup extract to mitigate their hepatic inflammation
      induced by a high-fat diet: a transcriptome analysis.
AB  - Effects of the administration of maple syrup extract (MSX) on hepatic gene
      expression were investigated in mice fed a high-fat diet. Gene annotation
      enrichment analysis based on gene ontology revealed some changes in the
      expression of genes related to lipid metabolism and the immune response in MSX
      fed mice. Detailed analysis of these data indicated that MSX ingestion mitigates
      hepatic inflammation. 

PMID- 25982264
TI  - Hyperglycemia associated with seizure control in status epilepticus.
AB  - BACKGROUND: Status epilepticus (SE) is a serious neurological condition and has a
      high mortality rate. Factors associated with seizure control measures in
      nonneurointensive care units (non-NICU) are limited. METHODS: Adult patients
      diagnosed with SE at Khon Kaen hospital, Thailand from October 1st, 2010 to
      September 30th, 2012 were enrolled. Patients were categorized as having
      controlled seizures and having uncontrolled seizures. Controlled seizures were
      defined as seizures that were aborted without any recurrence, while uncontrolled
      seizures were defined as unstoppable or recurrent seizures. Clinical factors were
      analyzed to find factors associated with uncontrolled SE. RESULTS: During the
      study period, there were 211 patients diagnosed with SE. Of those, 57 patients
      (27.01%) were in the group with controlled SE. Plasma glucose and serum albumin
      were two significant factors with adjusted ORs (95% CI) of 1.008 (1.001, 1.027)
      and 0.166 (0.059, 0.466) that differentiated patients with controlled seizures
      from patients with uncontrolled seizures. Central nervous system infections and
      cardiac arrests were also completely associated with the uncontrolled SE in the
      multivariate logistic analysis. CONCLUSIONS: In the etiology of SE, high plasma
      glucose and low serum albumin levels were associated with uncontrolled seizures
      in patients with SE in the non-NICU setting. This article is part of a Special
      Issue entitled "Status Epilepticus".

PMID- 25982263
TI  - Impact of graphene oxide on viability of Chinese hamster ovary and mouse hepatoma
      MH-22A cells.
AB  - The evaluation of the cyto- and bio-compatibility is a critical step in the
      development of graphene oxide (GO) as a new promising material for in vivo
      biomedical applications. In this study, we report the impact of GO, with and
      without the addition of bovine serum albumin, on healthy (Chinese hamster ovary)
      and a cancer (mouse hepatoma MH-22A) cells viability and the estimation of the
      intracellular distribution of GO inside the cells in vitro. The viability tests
      were performed using a colony formation assay. The intracellular distribution of
      GO was estimated using Raman spectroscopy and imaging. The viability of both cell
      lines decreased with increasing concentration of graphene oxide (12.5-50.0
      MUg/ml): in the case of Chinese hamster ovary cells viability decreased from 44%
      to 11%, in the case of mouse hepatoma MH-22A cells--from 22% to 3%. These cell
      lines significantly differed in their response to GO and GO-BSA formulations. The
      results of viability tests correlate with results of atomic force microscopy and
      Raman spectroscopy and imaging findings. The GO influence on cell morphology
      changes, cell structure, cells colony growth dynamics and GO accumulation inside
      the cells was higher in the case of mouse hepatoma MH-22A cells.

PMID- 25982265
TI  - Genetic mutations associated with status epilepticus.
AB  - This paper reports the results of a preliminary search of the literature aimed at
      identifying the genetic mutations reported to be strongly associated with status
      epilepticus. Genetic mutations were selected for inclusion if status epilepticus
      was specifically mentioned as a consequence of the mutation in standard genetic
      databases or in a case report or review article. Mutations in 122 genes were
      identified. The genetic mutations identified were found in only rare conditions
      (sometimes vanishingly rare) and mostly in infants and young children with
      multiple other handicaps. Most of the genetic mutations can be subdivided into
      those associated with cortical dysplasias, inborn errors of metabolism,
      mitochondrial disease, or epileptic encephalopathies and childhood syndromes.
      There are no identified 'pure status epilepticus genes'. The range of genes
      underpinning status epilepticus differs in many ways from the range of genes
      underpinning epilepsy, which suggests that the processes underpinning status
      epilepticus differ from those underpinning epilepsy. It has been frequently
      postulated that status epilepticus is the result of a failure of 'seizure
      termination mechanisms', but the wide variety of genes affecting very diverse
      biochemical pathways identified in this survey makes any unitary cause unlikely.
      The genetic influences in status epilepticus are likely to involve a wide range
      of mechanisms, some related to development, some to cerebral energy production,
      some to diverse altered biochemical pathways, some to transmitter and membrane
      function, and some to defects in networks or systems. The fact that many of the
      identified genes are involved with cerebral development suggests that status
      epilepticus might often be a system or network phenomenon. To date, there are
      very few genes identified which are associated with adult-onset status
      epilepticus (except in those with preexisting neurological damage), and this is
      disappointing as the cause of many adult-onset status epilepticus cases remains
      obscure. It has been suggested that idiopathic adult-onset status epilepticus
      might often have an immunological cause but no gene mutations which relate to
      immunological mechanisms were identified. Overall, the clinical utility of what
      is currently known about the genetics of status epilepticus is slight and the
      findings have had little impact on clinical treatment despite what has been a
      very large investment in money and time. New genetic technologies may result in
      the identification of further genes, but if the identified genetic defects confer
      only minor susceptibility, this is unlikely to influence therapy. It is also
      important to recognize that genetics has social implications in a way that other
      areas of science do not. This article is part of a Special Issue entitled "Status
      Epilepticus". 

PMID- 25982266
TI  - Prediction of rhythmic and periodic EEG patterns and seizures on continuous EEG
      with early epileptiform discharges.
AB  - BACKGROUND: Continuous EEG (cEEG) is necessary to document nonconvulsive seizures
      (NCS), nonconvulsive status epilepticus (NCSE), as well as rhythmic and periodic
      EEG patterns of 'ictal-interictal uncertainty' (RPPIIU) including periodic
      discharges, rhythmic delta activity, and spike-and-wave complexes in neurological
      intensive care patients. However, cEEG is associated with significant recording
      and analysis efforts. Therefore, predictors from short-term routine EEG with a
      reasonably high yield are urgently needed in order to select patients for
      evaluation with cEEG. OBJECTIVE: The aim of this study was to assess the
      prognostic significance of early epileptiform discharges (i.e., within the first
      30 min of EEG recording) on the following: (1) incidence of ictal EEG patterns
      and RPPIIU on subsequent cEEG, (2) occurrence of acute convulsive seizures during
      the ICU stay, and (3) functional outcome after 6 months of follow-up. METHODS: We
      conducted a separate analysis of the first 30 min and the remaining segments of
      prospective cEEG recordings according to the ACNS Standardized Critical Care EEG
      Terminology as well as NCS criteria and review of clinical data of 32
      neurological critical care patients. RESULTS: In 17 patients with epileptiform
      discharges within the first 30 min of EEG (group 1), electrographic seizures were
      observed in 23.5% (n = 4), rhythmic or periodic EEG patterns of 'ictal-interictal
      uncertainty' in 64.7% (n = 11), and neither electrographic seizures nor RPPIIU in
      11.8% (n = 2). In 15 patients with no epileptiform discharges in the first 30 min
      of EEG (group 2), no electrographic seizures were recorded on subsequent cEEG,
      RPPIIU were seen in 26.7% (n = 4), and neither electrographic seizures nor RPPIIU
      in 73.3% (n = 11). The incidence of EEG patterns on cEEG was significantly
      different between the two groups (p = 0.008). Patients with early epileptiform
      discharges developed acute seizures more frequently than patients without early
      epileptiform discharges (p = 0.009). Finally, functional outcome six months after
      discharge was significantly worse in patients with early epileptiform discharges
      (p=0.01). CONCLUSIONS: Epileptiform discharges within the first 30 min of EEG
      recording are predictive for the occurrence of ictal EEG patterns and for RPPIIU
      on subsequent cEEG, for acute convulsive seizures during the ICU stay, and for a
      worse functional outcome after 6 months of follow-up. This article is part of a
      Special Issue entitled Status Epilepticus.

PMID- 25982267
TI  - Influence of nutritional and physicochemical variables on PHB production from raw
      glycerol obtained from a Colombian biodiesel plant by a wild-type Bacillus
      megaterium strain.
AB  - Biodegradable polymers are currently viable alternatives to traditional synthetic
      polymers. For instance, polyhydroxybutyrate (PHB) is intracellularly produced and
      accumulated by Bacillus species, among others. This study reports several wild
      type Bacillus strains with the ability to accumulate PHB using raw glycerol from
      biodiesel production as the sole carbon source. Out of 15 strains from different
      sources, B. megaterium B2 was selected as the most promising strain for further
      statistical optimization of the medium composition. Plackett-Burman and central
      composite designs were used to establish key variables and optimal culture
      conditions for PHB production using both 250-mL shake flasks and a 7.5-L
      bioreactor. Temperature and concentrations of glycerol and Na2HPO4 are the
      experimental variables with the most significant influence on PHB production by
      B2. After 14 hours of fermentation in shake flasks with optimized medium, B2
      produced 0.43 g/L of PHB with a 34% accumulation in the cells. In contrast, under
      the same conditions, a maximum PHB concentration of 1.20 g/L in the bioreactor
      was reached at 11 hours. These values correspond to a 48% and 314% increase in
      PHB production compared to the initial culture conditions. These results suggest
      the potential of B2 as a PHB producer using raw glycerol, which is an
      inexpensive, abundant and readily available carbon source.

PMID- 25982268
TI  - Transplantation of Photoreceptor Precursors Isolated via a Cell Surface Biomarker
      Panel From Embryonic Stem Cell-Derived Self-Forming Retina.
AB  - Loss of photoreceptors due to retinal degeneration is a major cause of
      untreatable blindness. Cell replacement therapy, using pluripotent stem cell
      derived photoreceptor cells, may be a feasible future treatment. Achieving safe
      and effective cell replacement is critically dependent on the stringent selection
      and purification of optimal cells for transplantation. Previously, we
      demonstrated effective transplantation of post-mitotic photoreceptor precursor
      cells labelled by fluorescent reporter genes. As genetically labelled cells are
      not desirable for therapy, here we developed a surface biomarker cell selection
      strategy for application to complex pluripotent stem cell differentiation
      cultures. We show that a five cell surface biomarker panel
      CD73(+)CD24(+)CD133(+)CD47(+)CD15(-) facilitates the isolation of photoreceptor
      precursors from three-dimensional self-forming retina differentiated from mouse
      embryonic stem cells. Importantly, stem cell-derived cells isolated using the
      biomarker panel successfully integrate and mature into new rod photoreceptors in
      the adult mouse retinae after subretinal transplantation. Conversely, unsorted or
      negatively selected cells do not give rise to newly integrated rods after
      transplantation. The biomarker panel also removes detrimental proliferating cells
      prior to transplantation. Notably, we demonstrate how expression of the biomarker
      panel is conserved in the human retina and propose that a similar selection
      strategy will facilitate isolation of human transplantation-competent cells for
      therapeutic application.

PMID- 25982269
TI  - Monoclonal antibodies to HLA-E bind epitopes carried by unfolded beta2 m-free
      heavy chains.
AB  - Since HLA-E heavy chains accumulate free of their light beta2 -microglobulin
      (beta2 m) subunit, raising mAbs to folded HLA-E heterodimers has been difficult,
      and mAb characterization has been controversial. Herein, mAb W6/32 and 5 HLA-E
      restricted mAbs (MEM-E/02, MEM-E/07, MEM-E/08, DT9, and 3D12) were tested on
      denatured, acid-treated, and natively folded (both beta2 m-associated and beta2 m
      free) HLA-E molecules. Four distinct conformations were detected, including
      unusual, partially folded (and yet beta2 m-free) heavy chains reactive with mAb
      DT9. In contrast with previous studies, epitope mapping and substitution scan on
      thousands of overlapping peptides printed on microchips revealed that mAbs MEM
      E/02, MEM-E/07, and MEM-E/08 bind three distinct alpha1 and alpha2 domain
      epitopes. All three epitopes are linear since they span just 4-6 residues and are
      "hidden" in folded HLA-E heterodimers. They contain at least one HLA-E-specific
      residue that cannot be replaced by single substitutions with polymorphic HLA-A,
      HLA-B, HLA-C, HLA-F, and HLA-G residues. Finally, also the MEM-E/02 and 3D12
      epitopes are spatially distinct. In summary, HLA-E-specific residues are
      dominantly immunogenic, but only when heavy chains are locally unfolded.
      Consequently, the available mAbs fail to selectively bind conformed HLA-E
      heterodimers, and HLA-E expression may have been inaccurately assessed in some
      previous oncology, reproductive immunology, virology, and transplantation
      studies. 

PMID- 25982270
TI  - Crystal structure of the C-terminal domain of tubulin-binding cofactor C from
      Leishmania major.
AB  - Tubulin-binding cofactor C stimulates GTPase activity and contributes to the
      release of the heterodimeric alpha/beta-tubulin from a super-complex of tubulin
      monomers and two ancillary cofactors. We have determined the 2.2 A resolution
      crystal structure of the C-terminal domain of tubulin-binding cofactor C from
      Leishmania major based on single wavelength anomalous dispersion measurements
      targeting a selenomethionine derivative. Although previously predicted to consist
      of two domains the structure is best described as a single domain dominated by a
      right-handed beta-helix of five turns that form a triangular prism. One face of
      the prism is covered by the C-terminal residues leaving another face solvent
      exposed. Comparisons with an orthologous human GTPase activating protein match
      key residues involved in binding nucleotide and identify the face of the beta
      helix fold likely involved in interacting with the beta-tubulin:GTP complex. 

PMID- 25982272
TI  - Stromal fibroblasts facilitate cancer cell invasion by a novel invadopodia
      independent matrix degradation process.
AB  - Metastatic invasion of tumors into peripheral tissues is known to rely upon
      protease-mediated degradation of the surrounding stroma. This remodeling process
      uses complex, actin-based, specializations of the plasma membrane termed
      invadopodia that act both to sequester and release matrix metalloproteinases.
      Here we report that cells of mesenchymal origin, including tumor-associated
      fibroblasts, degrade substantial amounts of surrounding matrix by a mechanism
      independent of conventional invadopodia. These degradative sites lack the
      punctate shape of conventional invadopodia to spread along the cell base and are
      reticular and/or fibrous in character. In marked contrast to invadopodia, this
      degradation does not require the action of Src kinase, Cdc42 or Dyn2. Rather,
      inhibition of Dyn2 causes a marked upregulation of stromal matrix degradation.
      Further, expression and activity of matrix metalloproteinases are differentially
      regulated between tumor cells and stromal fibroblasts. This matrix remodeling by
      fibroblasts increases the invasive capacity of tumor cells, thereby illustrating
      how the tumor microenvironment can contribute to metastasis. These findings
      provide evidence for a novel matrix remodeling process conducted by stromal
      fibroblasts that is substantially more effective than conventional invadopodia,
      distinct in structural organization and regulated by disparate molecular
      mechanisms. 

PMID- 25982271
TI  - The nucleotide excision repair protein XPC is essential for bulky DNA adducts to
      promote interleukin-6 expression via the activation of p38-SAPK.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, and many
      are potent carcinogens. Benzo[a]pyrene (B[a]P), one of the best-studied PAHs, is
      metabolized ultimately to the genotoxin anti-B[a]P-7,8-dihydrodiol-9,10-epoxide
      (BPDE). BPDE triggers stress responses linked to gene expression, cell death and
      survival. So far, the underlying mechanisms that initiate these signal
      transduction cascades are unknown. Here we show that BPDE-induced DNA damage is
      recognized by DNA damage sensor proteins to induce activation of the stress
      activated protein kinase (SAPK) p38. Surprisingly, the classical DNA damage
      response, which involves the kinases ATM and ATR, is not involved in p38-SAPK
      activation by BPDE. Moreover, the induction of p38-SAPK phosphorylation also
      occurs in the absence of DNA strand breaks. Instead, increased phosphorylation of
      p38-SAPK requires the nucleotide excision repair (NER) and DNA damage sensor
      proteins XPC and mHR23B. Interestingly, other genotoxins such as cisplatin
      (CDDP), hydrogen peroxide and ultraviolet radiation also enhance XPC-dependent
      p38-SAPK phosphorylation. In contrast, anti-benzo[c]phenanthrene-3,4-dihydrodiol
      1,2-epoxide, the DNA adducts of which are not properly recognized by NER, does
      not trigger p38-SAPK activation. As a downstream consequence, expression and
      secretion of the pro-inflammatory cytokine interleukin-6 is induced by BPDE and
      CDDP in vitro and by CDDP in the murine lung, and depends on XPC. In conclusion,
      we describe a novel pathway in which DNA damage recognition by NER proteins
      specifically leads to activation of p38-SAPK to promote inflammatory gene
      expression. 

PMID- 25982273
TI  - LASP-1: a nuclear hub for the UHRF1-DNMT1-G9a-Snail1 complex.
AB  - Nuclear LASP-1 (LIM and SH3 protein-1) has a direct correlation with overall
      survival of breast cancer patients. In this study, immunohistochemical analysis
      of a human breast TMA showed that LASP-1 is absent in normal human breast
      epithelium but the expression increases with malignancy and is highly nuclear in
      aggressive breast cancer. We investigated whether the chemokines and growth
      factors present in the tumor microenvironment could trigger nuclear translocation
      of LASP-1.Treatment of human breast cancer cells with CXCL12, EGF and HRG, and
      HMEC-CXCR2 cells with CXCL8 facilitated nuclear shuttling of LASP-1. Data from
      the biochemical analysis of the nuclear and cytosolic fractions further confirmed
      the nuclear translocation of LASP-1 upon chemokine and growth factor treatment.
      CXCL12-dependent nuclear import of LASP-1 could be blocked by CXCR4 antagonist,
      AMD-3100. Knock down of LASP-1 resulted in alterations in gene expression leading
      to an increased level of cell-junction and extracellular matrix proteins and an
      altered cytokine secretory profile. Three-dimensional cultures of human breast
      cancer cells on Matrigel revealed an altered colony growth, morphology and
      arborization pattern in LASP-1 knockdown cells. Functional analysis of the LASP-1
      knockdown cells revealed increased adhesion to collagen IV and decreased invasion
      through the Matrigel. Proteomic analysis of immunoprecipitates of LASP-1 and
      subsequent validation approaches revealed that LASP-1 associated with the
      epigenetic machinery especially UHRF1, DNMT1, G9a and the transcription factor
      Snail1. Interestingly, LASP-1 associated with UHRF1, G9a, Snail1 and di- and tri
      methylated histoneH3 in a CXCL12-dependent manner based on immunoprecipitation
      and proximity ligation assays. LASP-1 also directly bound to Snail1 which may
      stabilize Snail1. Thus, nuclear LASP-1 appears to functionally serve as a hub for
      the epigenetic machinery. 

PMID- 25982274
TI  - miR-520h is crucial for DAPK2 regulation and breast cancer progression.
AB  - MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their
      interaction with 3'untranslated region of specific target mRNAs. Although the
      dysregulation of miRNAs has been identified in human cancer, only a few of these
      miRNAs have been functionally documented in breast cancer. Thus, defining the
      important miRNA and functional target involved in chemoresistance is an urgent
      need for human breast cancer treatment. In this study, we, for the first time,
      identified a key role of miRNA 520h (miR-520h) in drug resistance. Through
      protecting cells from paclitaxel-induced apoptosis, expression of miR-520h
      promoted the drug resistance of human breast cancer cells. Bioinformatics
      prediction, compensatory mutation and functional validation further confirmed the
      essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2)
      expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and
      knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h.
      Furthermore, we observed that higher level of miR-520h is associated with poor
      prognosis and lymph node metastasis in human breast cancer patients. These
      results show that miR-520h is not only an independent prognostic factor, but is
      also a potential functional target for future applications in cancer
      therapeutics. 

PMID- 25982275
TI  - Oncogenic activation of the PI3-kinase p110beta isoform via the tumor-derived
      PIK3Cbeta(D1067V) kinase domain mutation.
AB  - Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs widely in human
      cancers. Although somatic mutations in the PI3K pathway genes PIK3CA and PTEN are
      known to drive PI3K pathway activation and cancer growth, the significance of
      somatic mutations in other PI3K pathway genes is less clear. Here, we establish
      the signaling and oncogenic properties of a recurrent somatic mutation in the
      PI3K p110beta isoform that resides within its kinase domain (PIK3Cbeta(D1067V)).
      We initially observed PIK3Cbeta(D1067V) by exome sequencing analysis of an EGFR
      mutant non-small cell lung cancer (NSCLC) tumor biopsy from a patient with
      acquired erlotinib resistance. On the basis of this finding, we hypothesized that
      PIK3Cbeta(D1067V) might function as a novel tumor-promoting genetic alteration,
      and potentially an oncogene, in certain cancers. Consistent with this hypothesis,
      analysis of additional tumor exome data sets revealed the presence of
      PIK3Cbeta(D1067V) at low frequency in other patient tumor samples (including
      renal cell carcinoma, glioblastoma multiforme, head and neck squamous cell
      carcinoma, melanoma, thyroid carcinoma and endometrial carcinoma). Functional
      studies revealed that PIK3Cbeta(D1067V) promoted PI3K pathway signaling, enhanced
      cell growth in vitro, and was sufficient for tumor formation in vivo.
      Pharmacologic inhibition of PIK3Cbeta with TGX-221 (isoform-selective p110beta
      inhibitor) specifically suppressed growth in patient-derived renal-cell carcinoma
      cells with endogenous PIK3Cbeta(D1067V) and in NIH-3T3 and human EGFR-mutant lung
      adenocarcinoma cells engineered to express this mutant PI3K. In the EGFR-mutant
      lung adenocarcinoma cells, expression of PIK3Cbeta(D1067V) also promoted
      erlotinib resistance. Our data establish a novel oncogenic form of PI3K,
      revealing the signaling and oncogenic properties of PIK3Cbeta(D1067V) and its
      potential therapeutic relevance in cancer. Our findings provide new insight into
      the genetic mechanisms underlying PI3K pathway activation in human tumors and
      indicate that PIK3Cbeta(D1067V) is a rational therapeutic target in certain
      cancers. 

PMID- 25982277
TI  - Plexin-B1 signalling promotes androgen receptor translocation to the nucleus.
AB  - Semaphorins and their receptors plexins have diverse roles in many cancers
      affecting tumour growth, metastasis and angiogenesis. Plexin-B1, the receptor for
      semaphorin4D (Sema4D), has been implicated in prostate cancer where mutation of
      the gene and overexpression of the protein occur. It is not clear, however, as to
      which of the several Sema4D-activated signalling pathways downstream of plexin-B1
      function in prostate cancer progression. We show here that Sema4D/plexin-B1
      increases the expression of androgen-responsive genes and activates the
      transcriptional activity of the androgen receptor (AR). Activation of plexin-B1
      results in phosphorylation of AR at Serine 81, a site that is phosphorylated by
      nuclear kinases. Cell fractionation and immunocytochemistry studies demonstrated
      that the proportion of cells with AR in the nucleus increases significantly upon
      Sema4D treatment. The N-terminal (AF-1) domain of AR, which contains binding
      sites for transcription regulators, is not required for this response. Depletion
      of AR suppressed Sema4D-induced anchorage-independent growth of LNCaP and LNCaP
      LN3 cells, demonstrating the functional significance of these findings. These
      results show that Sema4D/plexin-B1 signalling promotes the translocation of AR to
      the nucleus and thereby enhances AR transcriptional activity. Plexin-B1 is
      therefore a promising target for cancer therapy, especially in low androgen
      situations such as those imposed by androgen deprivation therapy. 

PMID- 25982276
TI  - MALT1 is required for EGFR-induced NF-kappaB activation and contributes to EGFR
      driven lung cancer progression.
AB  - The transcription factor nuclear factor kappa B (NF-kappaB) has been implicated
      in having a crucial role in the tumorigenesis of many types of human cancers.
      Although epidermal growth factor receptor (EGFR) can directly activate NF-kappaB,
      the mechanism by which EGFR induces NF-kappaB activation and the role of NF
      kappaB in EGFR-associated tumor progression is still not fully defined. Herein,
      we found that mucosa-associated lymphoid tissue 1 (MALT1) is involved in EGFR
      induced NF-kappaB activation in cancer cells, and that MALT1 deficiency impaired
      EGFR-induced NF-kappaB activation. MALT1 mainly functions as a scaffold protein
      by recruiting E3 ligase TRAF6 to IKK complex to activate NF-kappaB in response to
      EGF stimulation. Functionally, MALT1 inhibition shows significant defects in EGFR
      associated tumor malignancy, including cell migration, metastasis and anchorage
      independent growth. To further access a physiological role of MALT1-dependent NF
      kappaB activation in EGFR-driven tumor progression, we generated triple
      transgenic mouse model (tetO-EGFR(L858R); CCSP-rtTA; Malt1(-/-)), in which mutant
      EGFR-driven lung cancer was developed in the absence of MALT1 expression. MALT1
      deficient mice show significantly less lung tumor burden when compared with its
      heterozygous controls, suggesting that MALT1 is required for the progression of
      EGFR-induced lung cancer. Mechanistically, MALT1 deficiency abolished both NF
      kappaB and STAT3 activation in vivo, which is a result of a defect of interleukin
      6 production. In comparison, MALT1 deficiency does not affect tumor progression
      in a mouse model (LSL-K-ras(G12D); CCSP-Cre; Malt1(-/-)) in which lung cancer is
      induced by expressing a K-ras mutant. Thus, our study has provided the cellular
      and genetic evidence that suggests MALT1-dependent NF-kappaB activation is
      important in EGFR-associated solid-tumor progression. 

PMID- 25982278
TI  - IFNgamma induces oxidative stress, DNA damage and tumor cell senescence via
      TGFbeta/SMAD signaling-dependent induction of Nox4 and suppression of ANT2.
AB  - Cellular senescence provides a biological barrier against tumor progression,
      often associated with oncogene-induced replication and/or oxidative stress,
      cytokine production and DNA damage response (DDR), leading to persistent cell
      cycle arrest. While cytokines such as tumor necrosis factor-alpha (TNFalpha) and
      interferon gamma (IFNgamma) are important components of senescence-associated
      secretome and induce senescence in, for example, mouse pancreatic beta-cancer
      cell model, their downstream signaling pathway(s) and links with oxidative stress
      and DDR are mechanistically unclear. Using human and mouse normal and cancer cell
      models, we now show that TNFalpha and IFNgamma induce NADPH oxidases Nox4 and
      Nox1, reactive oxygen species (ROS), DDR signaling and premature senescence.
      Unlike mouse tumor cells that required concomitant presence of IFNgamma and
      TNFalpha, short exposure to IFNgamma alone was sufficient to induce Nox4, Nox1
      and DDR in human cells. siRNA-mediated knockdown of Nox4 but not Nox1 decreased
      IFNgamma-induced DDR. The expression of Nox4/Nox1 required Janus kinase
      (JAK)/signal transducers and activators of transcription (STAT) signaling and the
      effect was mediated by downstream activation of transforming growth factor-beta
      (TGFbeta) secretion and consequent autocrine/paracrine activation of the
      TGFbeta/Smad pathway. Furthermore, the expression of adenine nucleotide
      translocase 2 (ANT2) was suppressed by IFNgamma contributing to elevation of ROS
      and DNA damage. In contrast to mouse B16 cells, inability of TC-1 cells to
      respond to IFNgamma/TNFalpha by DDR and senescence correlated with the lack of
      TGFbeta and Nox4 response, supporting the role of ROS induced by NADPH oxidases
      in cytokine-induced senescence. Overall, our data reveal differences between
      cytokine effects in mouse and human cells, and mechanistically implicate the
      TGFbeta/SMAD pathway, via induction of NADPH oxidases and suppression of ANT2, as
      key mediators of IFNgamma/TNFalpha-evoked genotoxicity and cellular senescence. 

PMID- 25982282
TI  - Frequent promoter hypermethylation of PTPRT increases STAT3 activation and
      sensitivity to STAT3 inhibition in head and neck cancer.
AB  - Signal transducer and activator of transcription 3 (STAT3) overactivation is a
      common event in many cancers, including head and neck squamous cell carcinoma
      (HNSCC), where STAT3 represents a promising therapeutic target. HNSCC is not
      characterized by frequent kinase mutations, in contrast to some malignancies
      where mutational activation of kinases upstream of STAT3 is common. Instead,
      STAT3 may be activated by loss-of-function of negative regulators of STAT3,
      including by promoter hypermethylation of PTPRT. Here we first analyzed The
      Cancer Genome Atlas data and determined that the PTPRT promoter is frequently
      hypermethylated in several cancers, including HNSCC (60.1% of tumors analyzed) in
      association with downregulation of PTPRT mRNA expression and upregulation of
      pSTAT3 expression. These findings were confirmed in an independent cohort of
      HNSCC tumors by methylation-specific PCR and immunohistochemistry. We demonstrate
      that PTPRT promoter methylation and gene silencing is reversible in HNSCC cells,
      leading to PTPRT-specific downregulation of pSTAT3 expression. We further show
      that PTPRT promoter methylation is significantly associated with sensitivity to
      STAT3 inhibition in HNSCC cells, suggesting that PTPRT promoter methylation may
      serve as a predictive biomarker for responsiveness to STAT3 inhibitors in
      clinical development. 

PMID- 25982281
TI  - Opportunities and challenges provided by crosstalk between signalling pathways in
      cancer.
AB  - During evolution, connections between the major signalling pathways were
      established to provide cells with an ability to deal with perturbations of
      homeostasis. However, these feedback and crosstalk mechanisms can become a
      liability in the treatment of cancer, as the inhibition of one cancer-relevant
      signalling pathway can lead to the activation of a secondary survival pathway
      that interferes with cancer drug efficacy. In this review, we discuss connections
      between signalling pathways in relation to cancer therapy and we evaluate the use
      of genetic approaches to identify pathway crosstalk. We also discuss how insight
      into connections between signalling pathways can be exploited to design powerful
      synthetic lethal drug combination therapies for the treatment of cancer. 

PMID- 25982280
TI  - Scribble acts as an oncogene in EMU-myc-driven lymphoma.
AB  - Scribble complex proteins maintain apicobasal polarity, regulate cell fate
      determination and function as tumour suppressors in epithelial tissue. Despite
      evidence that the function of Scribble is maintained in the lymphocyte lineage,
      we still understand little about its role as a tumour suppressor in
      haematological malignancies. Using the EMU-myc model of Burkitt's lymphoma we
      investigated the role of Scribble in lymphomagenesis. We found that contrary to
      its well-documented tumour suppressor role in epithelial tissue, loss of Scribble
      expression delayed the expansion of peripheral B cells and delayed the onset of
      EMU-myc-driven lymphoma. This was despite upregulated ERK phosphorylation levels
      in Scribble-deficient tumours, which are associated with loss of Scribble
      expression and the development of more aggressive Burkitt's lymphoma.
      Interestingly, the developmental stage of lymphoma was unaffected by Scribble
      expression challenging any role for Scribble in fate determination in the
      haematopoetic lineage. These data provide evidence for oncogenic properties of
      Scribble in Myc-driven B-cell lymphomagenesis, reinforcing recent findings that
      overexpression of a mutant form of Scribble can act as an oncogene in epithelial
      cells. Our results support the growing appreciation that the tumour regulatory
      functions of Scribble, and other polarity protein family members, are context
      dependent. 

PMID- 25982279
TI  - Targeting JAK kinase in solid tumors: emerging opportunities and challenges.
AB  - Various human malignancies are characterized by excessive activation of the Janus
      family of cytoplasmic tyrosine kinases (JAK) and their associated transcription
      factors STAT3 and STAT5. In the majority of solid tumors, this occurs in response
      to increased abundance of inflammatory cytokines in the tumor microenvironment
      prominently produced by infiltrating innate immune cells. Many of these cytokines
      share common receptor subunits and belong to the interleukin (IL)-6/IL-11, IL
      10/IL-22 and IL-12/IL-23 families. Therapeutic inhibition of the JAK/STAT3
      pathway potentially offers considerable benefit owing to the capacity of
      JAK/STAT3 signaling to promote cancer hallmarks in the tumor and its environment,
      including proliferation, survival, angiogenesis, tumor metabolism while
      suppressing antitumor immunity. This is further emphasized by the current
      successful clinical applications of JAK-specific small molecule inhibitors for
      the treatment of inflammatory disorders and hematopoietic malignancies. Here we
      review current preclinical applications for JAK inhibitors for the treatment of
      solid cancers in mice, with a focus on the most common malignancies emanating
      from oncogenic transformation of the epithelial mucosa in the stomach and colon.
      Emerging data with small molecule JAK-specific adenosine triphosphate-binding
      analogs corroborate genetic findings and suggest that interference with the
      JAK/STAT3 pathway may suppress the growth of the most common forms of sporadic
      colon cancers that arise from mutations of the APC tumor suppressor gene.
      Likewise inhibition of cytokine-dependent activation of the JAK/STAT3 pathway may
      also afford orthogonal treatment opportunities for other oncogene-addicted cancer
      cells that have gained drug resistance. 

PMID- 25982283
TI  - IMP3 promotes stem-like properties in triple-negative breast cancer by regulating
      SLUG.
AB  - IMP3 (insulin-like growth factor-2 mRNA binding protein 3) is an oncofetal
      protein whose expression is prognostic for poor outcome in several cancers.
      Although IMP3 is expressed preferentially in triple-negative breast cancer
      (TNBC), its function is poorly understood. We observed that IMP3 expression is
      significantly higher in tumor initiating than in non-tumor initiating breast
      cancer cells and we demonstrate that IMP3 contributes to self-renewal and tumor
      initiation, properties associated with cancer stem cells (CSCs). The mechanism by
      which IMP3 contributes to this phenotype involves its ability to induce the stem
      cell factor SOX2. IMP3 does not interact with SOX2 mRNA significantly or regulate
      SOX2 expression directly. We discovered that IMP3 binds avidly to SNAI2 (SLUG)
      mRNA and regulates its expression by binding to the 5' UTR. This finding is
      significant because SLUG has been implicated in breast CSCs and TNBC. Moreover,
      we show that SOX2 is a transcriptional target of SLUG. These data establish a
      novel mechanism of breast tumor initiation involving IMP3 and they provide a
      rationale for its association with aggressive disease and poor outcome. 

PMID- 25982284
TI  - Atorvastatin and fenofibrate combination induces the predominance of the large
      HDL subclasses and increased apo AI fractional catabolic rates in New Zealand
      white rabbits with exogenous hypercholesterolemia.
AB  - The anti-atherogenic properties of high-density lipoproteins (HDLs) may be
      related to their structure and metabolism. The HDL physicochemical
      characteristics that determine their plasma clearance during treatment with
      statins and fibrates are not well understood. In this study, we analyzed HDL-apo
      AI fractional catabolic rates (FCRs), size distributions, and the lipid
      composition of the HDL subclasses in New Zealand white rabbits with exogenous
      dyslipidemia that received low doses of atorvastatin and fenofibrate.
      Hypercholesterolemia decreased only partially with the combination of both drugs.
      HDL size distribution shifted toward larger particles among the groups of rabbits
      that received atorvastatin, fenofibrate, or their combination, compared with both
      the control group and the dyslipidemic group. The HDL subclasses were
      significantly rich in cholesterol in each of the groups compared with controls.
      The structural changes noted in the HDL subclasses were not associated with
      impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy
      and the drug combination group were all associated with a higher apo AI FCR value
      compared with both the dyslipidemic rabbits and the control group. In conclusion,
      the combination of atorvastatin and fenofibrate induced a more favorable HDL
      subclass profile than did the individual use of these drugs. Similarly, the apo
      AI FCR values were augmented in every group receiving drug treatment (either
      monotherapy or combination therapy) in the setting of hypercholesterolemia. The
      anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may
      be enhanced by the structural and metabolic modifications induced by the
      combination of atorvastatin and fenofibrate. 

PMID- 25982285
TI  - Association of chromosome 19 to lung cancer genotypes and phenotypes.
AB  - The Chromosome 19 Consortium, a part of the Chromosome-Centric Human Proteome
      Project (C-HPP, http://www.C-HPP.org ), is tasked with the understanding
      chromosome 19 functions at the gene and protein levels, as well as their roles in
      lung oncogenesis. Comparative genomic hybridization (CGH) studies revealed
      chromosome aberration in lung cancer subtypes, including ADC, SCC, LCC, and SCLC.
      The most common abnormality is 19p loss and 19q gain. Sixty-four aberrant genes
      identified in previous genomic studies and their encoded protein functions were
      further validated in the neXtProt database ( http://www.nextprot.org/ ). Among
      those, the loss of tumor suppressor genes STK11, MUM1, KISS1R (19p13.3), and BRG1
      (19p13.13) is associated with lung oncogenesis or remote metastasis. Gene
      aberrations include translocation t(15, 19) (q13, p13.1) fusion oncogene BRD4
      NUT, DNA repair genes (ERCC1, ERCC2, XRCC1), TGFbeta1 pathway activation genes
      (TGFB1, LTBP4), Dyrk1B, and potential oncogenesis protector genes such as NFkB
      pathway inhibition genes (NFKBIB, PPP1R13L) and EGLN2. In conclusion, neXtProt is
      an effective resource for the validation of gene aberrations identified in
      genomic studies. It promises to enhance our understanding of lung cancer
      oncogenesis. 

PMID- 25982286
TI  - Direct conjugation of peptides and 5-hydroxymethylcytosine in DNA.
AB  - Recent discovery of functional 5-hydroxymethylcytosine in vertebrate genomes
      prompted for elaboration of methods to localize this modification at the
      nucleotide resolution level. Among several covalent modification-based
      approaches, atypical activity of cytosine-5 DNA methyltransferases to couple
      small molecules to 5-hydroxymethylcytosine stands out for acceptance of broad
      range of ligands. We went further to explore the possibility for
      methyltransferase-maintained coupling of compounds possessing autonomous
      functions. Functionalization of DNA was achieved by direct conjugation of
      chemically synthesized peptides of regular structure. Sequence, residue, and
      position-specific coupling of DNA containing 5-hydroxymethylcytosine and
      different peptides has been demonstrated, with the nature of the resulting
      conjugates confirmed by protease treatment and mass spectrometry. Coupling
      products were compatible with affinity-driven separation from the unmodified DNA.
      This approach highlights an emerging avenue toward the enzymatic, sequence
      specific DNA functionalization, enabling a single step merge of the DNA and
      peptide moieties into a bifunctional entity. 

PMID- 25982287
TI  - Assessing exploitation experiences of girls and boys seen at a Child Advocacy
      Center.
AB  - The primary aim of this study was to describe the abuse experiences of sexually
      exploited runaway adolescents seen at a Child Advocacy Center (N=62). We also
      sought to identify risk behaviors, attributes of resiliency, laboratory results
      for sexually transmitted infection (STI) screens, and genital injuries from
      colposcopic exams. We used retrospective mixed-methods with in-depth forensic
      interviews, together with self-report survey responses, physical exams and chart
      data. Forensic interviews were analyzed using interpretive description analytical
      methods along domains of experience and meaning of sexual exploitation events.
      Univariate descriptive statistics characterized trauma responses and health
      risks. The first sexual exploitation events for many victims occurred as part of
      seemingly random encounters with procurers. Older adolescent or adult women
      recruited some youth working for a pimp. However, half the youth did not report a
      trafficker involved in setting up their exchange of sex for money, substances, or
      other types of consideration. 78% scored positive on the UCLA PTSD tool; 57%
      reported DSM IV criteria for problem substance use; 71% reported cutting
      behaviors, 75% suicidal ideation, and 50% had attempted suicide. Contrary to
      common depictions, youth may be solicited relatively quickly as runaways, yet
      exploitation is not always linked to having a pimp. Avoidant coping does not
      appear effective, as most patients exhibited significant symptoms of trauma.
      Awareness of variations in youth's sexual exploitation experiences may help
      researchers and clinicians understand potential differences in sequelae, design
      effective treatment plans, and develop community prevention programs. 

PMID- 25982288
TI  - Systematic review: the prevention of oesophageal stricture after endoscopic
      resection.
AB  - BACKGROUND: Extensive endoscopic resections for the treatment of early
      oesophageal neoplasia can result in fibro-inflammatory strictures that require
      repeated interventions, which significantly alter the patients' quality of life.
      AIMS: To review current evidence about the prevention of oesophageal strictures
      following endoscopic resections. METHODS: Systematic search of PubMed and Embase
      from inception to March 2015 using appropriate keywords. All original
      publications in English were included, and articles on the treatment of
      oesophageal stricture were excluded. RESULTS: Of the 461 hits, 62 studies were
      included in the analysis. Among the wound-protective strategies, polyglycolic
      acid sheets showed the most convincing evidence with a 37.5% stricture rate and
      excellent safety. Regenerative medicine, using cell sheets of autologous
      keratinocytes, resulted in a 25% stricture rate, although with cost and
      availability concerns. Among anti-proliferative treatment modalities, steroid
      treatment, either endoscopically injected triamcinolone in the resection wound or
      orally administered prednisolone, proved effective with an overall stricture rate
      of 13.5%, with safety concerns regarding late oesophageal perforations and
      infectious morbidity. Among mechanical treatment options, poorly effective and
      high-risk preventive balloon dilation tend to be replaced by prophylactic covered
      stent, with 18-28% stricture rates. CONCLUSIONS: Although oral or locally
      injected steroids are promising options, no currently available technique is
      sufficiently efficient and devoid of significant safety concerns to recommend its
      routine use for the prevention of strictures after extensive endoscopic
      resection. Improving our knowledge in the mechanisms of oesophageal wound healing
      will guide the development of novel methods for stricture prevention.

PMID- 25982289
TI  - Gastrointestinal Autoimmunity Associated With Loss of Central Tolerance to
      Enteric alpha-Defensins.
AB  - BACKGROUND & AIMS: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
      (APECED) is an autoimmune disorder characterized by chronic mucocutaneous
      candidiasis, hypoparathyroidism, and adrenal insufficiency, but patients also
      develop intestinal disorders. APECED is an autosomal recessive disorder caused by
      mutations in the autoimmune regulator (AIRE, which regulates immune tolerance)
      that allow self-reactive T cells to enter the periphery. Enteric alpha-defensins
      are antimicrobial peptides secreted by Paneth cells. Patients with APECED
      frequently have gastrointestinal symptoms and seroreactivity against secretory
      granules of Paneth cells. We investigated whether enteric alpha-defensins are
      autoantigens in humans and mice with AIRE deficiency. METHODS: We analyzed
      clinical data, along with serum and stool samples and available duodenal biopsies
      from 50 patients with APECED collected from multiple centers in Europe. Samples
      were assessed for expression of defensins and other molecules by quantitative
      reverse transcription polymerase chain reaction and flow cytometry; levels of
      antibodies and other proteins were measured by immunohistochemical and immunoblot
      analyses. Histologic analyses were performed on biopsy samples. We used Aire(-/-)
      mice as a model of APECED, and studied the effects of transferring immune cells
      from these mice to athymic mice. RESULTS: Enteric defensins were detected in
      extraintestinal tissues of patients with APECED, especially in medullary thymic
      epithelial cells. Some patients with APECED lacked Paneth cells and were
      seropositive for defensin-specific autoantibodies; the presence of autoantibodies
      correlated with frequent diarrhea. Aire(-/-) mice developed defensin-specific T
      cells. Adoptive transfer of these T cells to athymic mice resulted in T-cell
      infiltration of the gut, loss of Paneth cells, microbial dysbiosis, and the
      induction of T-helper 17 cell-mediated autoimmune responses resembling those
      observed in patients with APECED. CONCLUSIONS: In patients with APECED, loss of
      AIRE appears to cause an autoimmune response against enteric defensins and loss
      of Paneth cells. Aire(-/-) mice developed defensin-specific T cells that cause
      intestinal defects similar to those observed in patients with APECED. These
      findings provide a mechanism by which loss of AIRE-mediated immune tolerance
      leads to intestinal disorders in patients with APECED.

PMID- 25982291
TI  - Eye movements as probes of lexico-semantic processing in a patient with primary
      progressive aphasia.
AB  - Eye movement trajectories during a verbally cued object search task were used as
      probes of lexico-semantic associations in an anomic patient with primary
      progressive aphasia. Visual search was normal on trials where the target object
      could be named but became lengthy and inefficient on trials where the object
      failed to be named. The abnormality was most profound if the noun denoting the
      object could not be recognized. Even trials where the name of the target object
      was recognized but not retrieved triggered abnormal eye movements, demonstrating
      that retrieval failures can have underlying associative components despite intact
      comprehension of the corresponding noun. 

PMID- 25982290
TI  - Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies,
      Mechanisms, and Outlook.
AB  - The community of microorganisms within the human gut (or microbiota) is critical
      to health and functions with a level of complexity comparable to that of an organ
      system. Alterations of this ecology (or dysbiosis) have been implicated in a
      number of disease states, and the prototypical example is Clostridium difficile
      infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to
      durably alter the gut microbiota of the recipient and has shown efficacy in the
      treatment of patients with recurrent CDI. There is hope that FMT may eventually
      prove beneficial for the treatment of other diseases associated with alterations
      in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome,
      and metabolic syndrome, to name a few. Although the basic principles that
      underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are
      becoming apparent, further research is needed to understand the possible role of
      FMT in these other conditions. Although relatively simple to perform, questions
      regarding both short-term and long-term safety as well as the complex and rapidly
      evolving regulatory landscape has limited widespread use. Future work will focus
      on establishing best practices and more robust safety data than exist currently,
      as well as refining FMT beyond current "whole-stool" transplants to increase
      safety and tolerability. Encapsulated formulations, full-spectrum stool-based
      products, and defined microbial consortia are all in the immediate future. 

PMID- 25982292
TI  - In vitro inhibition effect of some coumarin compounds on purified human serum
      paraoxonase 1 (PON1).
AB  - Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein
      associated, calcium-dependent enzyme that hydrolyses aromatic esters,
      organophosphates and lactones and can protect the low-density lipoprotein against
      oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic
      coumarin derivatives (1-20) on purified PON1 activity was investigated. Among
      these compounds, derivatives 11-20 are water soluble. In investigated compounds,
      compounds 6 and 13 were found the most active (IC50 = 35 and 34 uM) for PON1,
      respectively. The present study has demonstrated that PON1 activity is very
      highly sensitive to studied coumarin derivatives. 

PMID- 25982293
TI  - Management of the aortic arch and descending thoracic aorta for acute type A
      dissection: Moving away from the "less is more" paradigm.

PMID- 25982294
TI  - Protecting the neonatal brain: Finding, treating, and preventing seizures.

PMID- 25982295
TI  - Four-branched graft with stent hybrid prosthesis for single-stage treatment of
      chronic aortic arch pathology.

PMID- 25982297
TI  - SPIRITT: A Randomized, Multicenter, Phase II Study of Panitumumab with FOLFIRI
      and Bevacizumab with FOLFIRI as Second-Line Treatment in Patients with
      Unresectable Wild Type KRAS Metastatic Colorectal Cancer.
AB  - BACKGROUND: Second-line treatment with chemotherapy and anti-epidermal growth
      factor receptor or anti-vascular endothelial growth factor antibodies improves
      outcomes in patients with wild type Kirsten rat sarcoma viral oncogene homolog
      (KRAS) metastatic colorectal cancer (mCRC). The choice of biological agent in
      second-line mCRC remains unclear. In this randomized, phase II estimation trial,
      we compared FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) in combination
      with panitumumab or bevacizumab in patients with disease progression during
      oxaliplatin-based chemotherapy and bevacizumab. PATIENTS AND METHODS: One hundred
      eighty-two patients were randomized to FOLFIRI with panitumumab or bevacizumab.
      The primary end point was progression-free survival (PFS). Secondary end points
      included overall survival (OS), objective response rate (ORR), and safety.
      RESULTS: PFS was similar between arms, with a hazard ratio (HR) of 1.01 (95%
      confidence interval [CI], 0.68-1.50; P = .97). Median PFS was 7.7 months (95% CI,
      5.7-11.8) in the panitumumab arm and 9.2 months (95% CI, 7.8-10.6) in the
      bevacizumab arm. OS was also similar between arms, with an HR of 1.06 (95% CI,
      0.75-1.49; P = .75). Median OS was 18.0 months (95% CI, 13.5-21.7) in the
      panitumumab arm and 21.4 months (95% CI, 16.5-24.6) in the bevacizumab arm. ORR
      was 32% (95% CI, 23%-43%) in the panitumumab arm and 19% (95% CI, 11%-29%) in the
      bevacizumab arm. Skin disorders, diarrhea, hypomagnesemia, hypokalemia,
      dehydration, and hypotension were more frequent in the panitumumab arm.
      Neutropenia was more frequent in the bevacizumab-containing arm. CONCLUSION:
      Panitumumab or bevacizumab with FOLFIRI as second-line treatment had efficacy
      similar in patients whose disease progressed during oxaliplatin-based
      chemotherapy with bevacizumab, with expected toxicities. The development of more
      accurate biomarkers might help caregivers and patients to better choose between
      therapies for individual patients.

PMID- 25982296
TI  - Manganese homeostasis in the nervous system.
AB  - Manganese (Mn) is an essential heavy metal that is naturally found in the
      environment. Daily intake through dietary sources provides the necessary amount
      required for several key physiological processes, including antioxidant defense,
      energy metabolism, immune function and others. However, overexposure from
      environmental sources can result in a condition known as manganism that features
      symptomatology similar to Parkinson's disease (PD). This disorder presents with
      debilitating motor and cognitive deficits that arise from a neurodegenerative
      process. In order to maintain a balance between its essentiality and
      neurotoxicity, several mechanisms exist to properly buffer cellular Mn levels.
      These include transporters involved in Mn uptake, and newly discovered Mn efflux
      mechanisms. This review will focus on current studies related to mechanisms
      underlying Mn import and export, primarily the Mn transporters, and their
      function and roles in Mn-induced neurotoxicity. Though and essential metal,
      overexposure to manganese may result in neurodegenerative disease analogous to
      Parkinson's disease. Manganese homeostasis is tightly regulated by transporters,
      including transmembrane importers (divalent metal transporter 1, transferrin and
      its receptor, zinc transporters ZIP8 and Zip14, dopamine transporter, calcium
      channels, choline transporters and citrate transporters) and exporters
      (ferroportin and SLC30A10), as well as the intracellular trafficking proteins
      (SPCA1 and ATP12A2). A manganese-specific sensor, GPP130, has been identified,
      which affords means for monitoring intracellular levels of this metal. 

PMID- 25982299
TI  - Twice cutting method reduces tibial cutting error in unicompartmental knee
      arthroplasty.
AB  - BACKGROUND: Bone cutting error can be one of the causes of malalignment in
      unicompartmental knee arthroplasty (UKA). The amount of cutting error in total
      knee arthroplasty has been reported. However, none have investigated cutting
      error in UKA. The purpose of this study was to reveal the amount of cutting error
      in UKA when open cutting guide was used and clarify whether cutting the tibia
      horizontally twice using the same cutting guide reduced the cutting errors in
      UKA. METHODS: We measured the alignment of the tibial cutting guides, the first
      cut cutting surfaces and the second cut cutting surfaces using the navigation
      system in 50 UKAs. Cutting error was defined as the angular difference between
      the cutting guide and cutting surface. RESULTS: The mean absolute first-cut
      cutting error was 1.9 degrees  (1.1 degrees  varus) in the coronal plane and 1.1
      degrees  (0.6 degrees  anterior slope) in the sagittal plane, whereas the mean
      absolute second-cut cutting error was 1.1 degrees  (0.6 degrees  varus) in the
      coronal plane and 1.1 degrees  (0.4 degrees  anterior slope) in the sagittal
      plane. Cutting the tibia horizontally twice reduced the cutting errors in the
      coronal plane significantly (P<0.05). CONCLUSION: Our study demonstrated that in
      UKA, cutting the tibia horizontally twice using the same cutting guide reduced
      cutting error in the coronal plane.

PMID- 25982298
TI  - A comprehensive in vivo kinematic, quantitative MRI and functional evaluation
      following ACL reconstruction--A comparison between mini-two incision and
      anteromedial portal femoral tunnel drilling.
AB  - BACKGROUND: Multiple techniques are used for femoral tunnel drilling in ACL
      reconstruction, including the Mini-two Incision Method (MT) and Anteromedial
      Portal Technique (AM). Both techniques allow for independent placement of the
      femoral tunnel, though there are no reports comparing kinematics and cartilage
      health after these reconstructions. We hypothesized that both techniques would
      result in the restoration of normal knee kinematics and show no evidence of early
      cartilage degeneration. METHODS: A total of 20 patients were evaluated one year
      after ACL reconstruction, including 10 patients after MT and 10 patients after
      AM. MR-imaging was acquired bilaterally with the knee loaded in extension and
      flexion to evaluate the kinematics of the reconstructed knee compared with the
      normal knee. Quantitative cartilage imaging was obtained and compared with 10
      matched control subjects. The Marx Activity Rating Scale and KOOS survey were
      administered. RESULTS: The tibia was positioned significantly more anteriorly in
      extension and flexion relative to the contralateral knee for the MT group. The
      tibial position in the AM group was not significantly different from the
      patient's contralateral knee. T1rho values in the central-medial tibia were
      significantly elevated in the MT group compared with the Control group. KOOS
      Symptom scores were significantly better for the MT group compared with the AM
      group. CONCLUSIONS: We have observed in vivo differences in knee kinematics and
      early cartilage degeneration between patients following MT and AM ACL
      reconstructions. Both techniques allow for anatomic ACL reconstruction, though
      the MT group shows significant early differences compared with the patient's
      normal knee.

PMID- 25982300
TI  - The UK National Ligament Registry Report 2015.

PMID- 25982301
TI  - An Integrative Literature Review of the Factors That Contribute to Professional
      Nurses and Midwives Making Sound Clinical Decisions.
AB  - PURPOSE: To identify available literature concerning the factors that contribute
      to nurses and midwives making sound clinical decisions. METHOD: This is an
      integrative literature review. FINDINGS: Thirty-eight articles revealed four main
      domains that influence nurses' and midwives' clinical decision making-nurses and
      midwives' personal characteristics (n = 30), e.g., clinical experience;
      organizational factors (n = 26), e.g., colleagues; patient characteristics (n =
      26), e.g., physical and clinical status; and environmental factors (n = 9), e.g.,
      time. These four domains of factors combined influence sound clinical decision
      making in the context of nursing and midwifery. CONCLUSIONS: Understanding the
      role of the factors influencing clinical decision making will help to improve
      patient and health outcomes. PRACTICE IMPLICATIONS: Further understanding about
      the extent of the impact some factors have on clinical decision making is needed.

PMID- 25982302
TI  - Preparing general practitioners to receive cancer patients following treatment in
      secondary care: a qualitative study.
AB  - BACKGROUND: Many patients consider the interface between secondary and primary
      care difficult, and in particular, the transition of care between these different
      parts of the healthcare system presents problems. This interface has long been
      recognized as a critical point for quality of care. The purpose of our study is
      to formulate solutions to problems identified by cancer patients and healthcare
      professionals during the transition from hospital back to general practice on
      completion of primary treatment for cancer. METHODS: A qualitative study based on
      focus groups at a seminar for professionals in both primary and secondary
      healthcare. Participants discussed solutions to problems which had previously
      been identified in patient interviews and in focus groups with general
      practitioners (GPs), hospital doctors, and nursing staff. The data were analyzed
      using framework analysis. RESULTS: Solutions, endorsed by all groups at the
      seminar to improve transition back to general practice after primary treatment
      for cancer, were: 1) To add nurses' discharge letters addressing psychosocial
      matters to medical discharge letters; 2) To send medical discharge letters
      earlier from some hospital departments to GPs; 3) To provide plans and future
      affiliations for patients when they leave a department, and 4) To arrange a
      return visit to general practice dedicated to discussion of the patients' cancer
      disease and the treatment experience. CONCLUSIONS: The transition of care of
      cancer patients appears too complex to be coordinated by administrative standards
      alone. We recommend that healthcare professionals are more engaged and present in
      the coordination of care across organizational boundaries.

PMID- 25982303
TI  - Yolk-Shell Porous Microspheres of Calcium Phosphate Prepared by Using Calcium L
      Lactate and Adenosine 5'-Triphosphate Disodium Salt: Application in Protein/Drug
      Delivery.
AB  - A facile and environmentally friendly approach has been developed to prepare yolk
      shell porous microspheres of calcium phosphate by using calcium L-lactate
      pentahydrate (CL) as the calcium source and adenosine 5'-triphosphate disodium
      salt (ATP) as the phosphate source through the microwave-assisted hydrothermal
      method. The effects of the concentration of CL, the microwave hydrothermal
      temperature, and the time on the morphology and crystal phase of the product are
      investigated. The possible formation mechanism of yolk-shell porous microspheres
      of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and
      ibuprofen (IBU) are used to explore the application potential of yolk-shell
      porous microspheres of calcium phosphate in protein/drug loading and delivery.
      The experimental results indicate that the as-prepared yolk-shell porous
      microspheres of calcium phosphate have relatively high protein/drug loading
      capacity, sustained protein/drug release, favorable pH-responsive release
      behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the
      yolk-shell porous microspheres of calcium phosphate have promising applications
      in various biomedical fields such as protein/drug delivery. 

PMID- 25982304
TI  - The role of the concept of biologically effective dose (BED) in treatment
      planning in radiosurgery.
AB  - Radiosurgery (RS) treatment times vary, even for the same prescription dose, due
      to variations in the collimator size, the number of iso-centres/beams/arcs used
      and the time gap between each of these exposures. The biologically effective dose
      (BED) concept, incorporating fast and slow components of repair, was used to show
      the likely influence of these variables for Gamma Knife patients with Vestibular
      Schwannomas. Two patients plans were selected, treated with the Model B Gamma
      Knife, these representing the widest range of treatment variables; iso-centre
      numbers 3 and 13, overall treatment times 25.4 and 129.6 min, prescription dose
      14 Gy. These were compared with 3 cases treated with the Perfexion((r)) Gamma
      Knife. The iso-centre number varied between 11 and 18, treatment time 35.7 - 74.4
      min, prescription dose 13 Gy. In the longer Model B Gamma Knife treatment plan
      the 14 Gy iso-dose was best matched by the 58 Gy2.47 iso-BED line, although
      higher and lower BED values were associated with regions on the prescription iso
      dose. The equivalent value for the shorter treatment was 85 Gy2.47. BED volume
      histograms showed that a BED of 85 Gy2.47 only covered ~65% of the target in the
      plan with the longer overall treatment time. The corresponding BED values for the
      3 cases, treated with the Perfexion((r)) Gamma Knife, were 59.5, 68.5 and 71.5
      Gy2.47. In conclusion BED calculations, taking account of the repair of sublethal
      damage, may indicate the importance of reporting overall time to reflect the
      biological effectiveness of the total physical dose applied.

PMID- 25982305
TI  - Acceptability of financial incentives for breastfeeding: thematic analysis of
      readers' comments to UK online news reports.
AB  - BACKGROUND: Whilst it is recommended that babies are breastfed exclusively for
      the first six months, many mothers do not maintain breastfeeding for this length
      of time. Previous research confirms that women and midwives value financial
      incentives for breastfeeding, but limited research has explored the wider
      acceptability of these interventions to the general public. This paper examines
      opinion towards financial incentives for breastfeeding using reader responses to
      UK on-line media coverage of a study undertaken in this area. METHODS: This study
      used netnography to undertake a thematic analysis of 3,373 reader comments posted
      in response to thirteen articles, published in November 2013, which reported
      findings from a feasibility study of financial incentives for breastfeeding. All
      articles were published on one of six UK news websites that achieved a monthly
      audience of at least five million viewers across laptop and desktop computers and
      mobile devices during April-May 2013. RESULTS: Nine analytical themes were
      identified, with a majority view that financial incentives for breastfeeding are
      unacceptable. These themes cover a range of opinions: from negligent parents
      unable to take responsibility for their own actions; through to psychologically
      vulnerable members of society who should be protected from coercion and
      manipulation; to capable and responsible women who can, and should be allowed to,
      make their own decisions. Many views focused on the immediate costs of the
      intervention, concluding that this was something that was currently unaffordable
      to fund (e.g. by the NHS). Others contrasted the value of the incentive against
      other 'costs' of breastfeeding. There was some consideration of the issue of cost
      effectiveness and cost-saving, where the potential future benefit from initial
      investment was identified. Many commenters identified that financial incentives
      do not address the many structural and cultural barriers to breastfeeding.
      CONCLUSIONS: Overall, those commenting on the on-line UK news articles viewed
      financial incentives for breastfeeding as unacceptable and that alternative,
      structural, interventions were likely to be more effective. Further consideration
      of how best to conduct internet-based qualitative research to elicit opinion
      towards public health issues is required.

PMID- 25982306
TI  - Microarray-based genotyping and detection of drug-resistant HBV mutations from
      620 Chinese patients with chronic HBV infection.
AB  - BACKGROUND: Research has shown that hepatitis B virus (HBV) genotypes are closely
      linked to the clinical manifestations, treatment, and prognosis of the disease.
      OBJECTIVE: To study the association between genotype and drug-resistant HBV
      mutations in 620 Chinese patients with chronic HBV infection. METHODS: HBV DNA
      levels were determined using real-time quantitative PCR in plasma samples.
      Microarrays were performed for the simultaneous detection of HBV genotypes
      (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the
      samples analyzed using microarrays was selected randomly and the data were
      confirmed using direct DNA sequencing. RESULTS: Most samples were genotype C
      (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient
      samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of
      these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)
      resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations
      (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and
      either adefovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out
      of the 620 patient samples, 64.0% (397/620) were also detected with the precore
      stop-codon mutation (G1896A) by microarray assay. CONCLUSION: The results of the
      current study revealed that the prevalence of nucleotide analogs (NA)-resistance
      in Chinese hospitalized HBV-positive patients was so low that intensive
      nucleotide analogs (NA)-resistance testing before nucleotide analog (NA)
      treatment might not be required. In addition, the present study suggests that
      chronic HBV patients with genotype C were infected with fitter viruses and had an
      increased prevalence of nucleotide analogs (NA)-resistance mutations compared to
      genotype B virus.

PMID- 25982308
TI  - Advanced Cancer in the Canadian Breast Screening Trials.

PMID- 25982307
TI  - Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3
      glomerulopathy.
AB  - C3 glomerulopathy (C3G) defines a group of untreatable ultra-rare renal diseases
      caused by uncontrolled activation of the alternative complement pathway. Nearly
      half of patients progress to end stage renal failure within 10 years. Cp40, a
      second-generation compstatin analog in clinical development, is a 14 amino-acid
      cyclic peptide that selectively inhibits complement activation in humans and non
      human primates by binding to C3 and C3b. We hypothesized that by targeting C3
      Cp40 would provide an effective treatment for C3G. By investigating its effects
      in vitro using multiple assays of complement activity, we show that Cp40 prevents
      complement-mediated lysis of sheep erythrocytes in sera from C3G patients,
      prevents complement dysregulation in the presence of patient-derived
      autoantibodies to the C3 and C5 convertases, and prevents complement
      dysregulation associated with disease-causing genetic mutations. In aggregate,
      these data suggest that Cp40 may offer a novel and promising therapeutic option
      to C3G patients as a disease-specific, targeted therapy. As such, Cp40 could
      represent a major advance in the treatment of this disease. 

PMID- 25982309
TI  - Multiple Object Tracking Reveals Object-Based Grouping Interference in Children
      with ASD.
AB  - The multiple object tracking (MOT) paradigm has proven its value in targeting a
      number of aspects of visual cognition. This study used MOT to investigate the
      effect of object-based grouping, both in children with and without autism
      spectrum disorder (ASD). A modified MOT task was administered to both groups, who
      had to track and distinguish four targets that moved randomly amongst four
      distracters, irrespective of the grouping condition. No group difference was
      revealed between children with and without ASD: both showed adequate MOT
      abilities and a similar amount of grouping interference. Implications of the
      current result are considered for previous MOT studies, the developmental
      trajectory of perceptual grouping, and the idea of heightened sensitivity to task
      characteristics in ASD.

PMID- 25982310
TI  - Vocational Rehabilitation Service Patterns and Outcomes for Individuals with
      Autism of Different Ages.
AB  - Young adults with autism spectrum disorders (ASD) often experience employment
      difficulties. Using Rehabilitation Service Administration data (RSA-911), this
      study investigated the service patterns and factors related to the employment
      outcomes of individuals with ASD in different age groups. Hierarchical logistic
      regression analyses were conducted to examine the effects of demographic and
      vocational rehabilitation (VR) service variables on employment outcomes in each
      age group. The results show that transition youth made up the largest portion of
      VR service users among the ASD population, yet they have the worst employment
      outcomes across all age groups. Factors that are significantly associated with
      increased odds for employment in each age group were identified. Implications
      from systemic, practical, and research perspectives are also provided. 

PMID- 25982312
TI  - Andragogy: a medical student's response.

PMID- 25982311
TI  - Reduction of Aggressive Episodes After Repeated Transdermal Nicotine
      Administration in a Hospitalized Adolescent with Autism Spectrum Disorder.
AB  - Aggression remains a major cause of morbidity in patients with autism spectrum
      disorder (ASD). Current pharmacotherapy for aggression is not always effective
      and is often associated with morbidity. Nicotinic acetylcholinergic
      neurotransmission may play a prominent role in ASD pathophysiology based on human
      and animal studies, and preclinical studies show nicotine administration can
      reduce aggression-related behaviors. Transdermal nicotine has been used to treat
      agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we
      report the use of transdermal nicotine as an adjunctive medication to treat
      aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently
      well tolerated, and reduced the need for emergency medication and restraint.
      These findings suggest further study of transdermal nicotine for aggression
      comorbid with ASD is warranted. 

PMID- 25982313
TI  - Shoshin Beriberi in Critically-Ill patients: case series.
AB  - Thiamine plays a fundamental role in cellular metabolism. The classical syndrome
      caused by thiamine deficiency is beriberi, and its fulminant variant, once
      considered an uncommon finding, is now encountered among the critically ill.We
      present a case series of four critically ill non-septic non-alcoholic patients
      with severe lactic acidosis and refractory cardio-circulatory collapse caused by
      acute fulminant beriberi, which drastically responded to thiamine
      administration.In critical care settings, increased awareness of this life
      threatening but reversible condition is a requirement, especially among patients
      receiving parenteral nutrition and those with unexplained recalcitrant lactic
      acidosis. 

PMID- 25982314
TI  - GermlncRNA: a unique catalogue of long non-coding RNAs and associated regulations
      in male germ cell development.
AB  - Spermatogenic failure is a major cause of male infertility, which affects
      millions of couples worldwide. Recent discovery of long non-coding RNAs (lncRNAs)
      as critical regulators in normal and disease development provides new clues for
      delineating the molecular regulation in male germ cell development. However, few
      functional lncRNAs have been characterized to date. A major limitation in
      studying lncRNA in male germ cell development is the absence of germ cell
      specific lncRNA annotation. Current lncRNA annotations are assembled by
      transcriptome data from heterogeneous tissue sources; specific germ cell
      transcript information of various developmental stages is therefore under
      represented, which may lead to biased prediction or fail to identity important
      germ cell-specific lncRNAs. GermlncRNA provides the first comprehensive web-based
      and open-access lncRNA catalogue for three key male germ cell stages, including
      type A spermatogonia, pachytene spermatocytes and round spermatids. This
      information has been developed by integrating male germ transcriptome resources
      derived from RNA-Seq, tiling microarray and GermSAGE. Characterizations on lncRNA
      associated regulatory features, potential coding gene and microRNA targets are
      also provided. Search results from GermlncRNA can be exported to Galaxy for
      downstream analysis or downloaded locally. Taken together, GermlncRNA offers a
      new avenue to better understand the role of lncRNAs and associated targets during
      spermatogenesis. Database URL: http://germlncrna.cbiit.cuhk.edu.hk/

PMID- 25982315
TI  - GraP: platform for functional genomics analysis of Gossypium raimondii.
AB  - Cotton (Gossypium spp.) is one of the most important natural fiber and oil crops
      worldwide. Improvement of fiber yield and quality under changing environments
      attract much attention from cotton researchers; however, a functional analysis
      platform integrating omics data is still missing. The success of cotton genome
      sequencing and large amount of available transcriptome data allows the
      opportunity to establish a comprehensive analysis platform for integrating these
      data and related information. A comprehensive database, Platform of Functional
      Genomics Analysis in Gossypium raimondii (GraP), was constructed to provide multi
      dimensional analysis, integration and visualization tools. GraP includes updated
      functional annotation, gene family classifications, protein-protein interaction
      networks, co-expression networks and microRNA-target pairs. Moreover, gene set
      enrichment analysis and cis-element significance analysis tools are also provided
      for gene batch analysis of high-throughput data sets. Based on these effective
      services, GraP may offer further information for subsequent studies of functional
      genes and in-depth analysis of high-throughput data. GraP is publically
      accessible at http://structuralbiology.cau.edu.cn/GraP/, with all data available
      for downloading. 

PMID- 25982316
TI  - Silk structure and degradation.
AB  - To investigate the structure of silk and its degradation properties, we have
      monitored the structure of silk using scanning electron microscopy and frozen
      sections. Raw silk and degummed raw silk were immersed in four types of
      degradation solutions for 156 d to observe their degradation properties. The
      subcutaneous implants in rats were removed after 7, 14, 56, 84, 129, and 145 d
      for frozen sectioning and subsequent staining with hematoxylin and eosin (H.E.),
      DAPI, Beta-actin and Collagen I immunofluorescence staining. The in vitro weight
      loss ratio of raw silk and degummed raw silk in water, PBS, DMEM and DMEM
      containing 10% FBS (F-DMEM) were, respectively, 14%/11%, 12.5%/12.9%,
      11.1%/14.3%, 8.8%/11.6%. Silk began to degrade after 7 d subcutaneous
      implantation and after 145 d non-degraded silk was still observed. These findings
      suggest the immunogenicity of fibroin and sericin had no essential difference. In
      the process of in vitro degradation of silk, the role of the enzyme is not
      significant. The in vivo degradation of silk is related to phagocytotic activity
      and fibroblasts may be involved in this process to secrete collagen. This study
      also shows the developing process of cocoons and raw silk. 

PMID- 25982317
TI  - Effects of CaCl2 hydrothermal treatment of titanium implant surfaces on early
      epithelial sealing.
AB  - Improvement of oral epithelial adhesion to titanium (Ti) may significantly
      enhance the efficacy of dental implants. We aimed to investigate whether calcium
      chloride (CaCl2) hydrothermally treated (HT) Ti could promote sealing of the peri
      implant epithelium (PIE) around the implant. Right maxillary first molars were
      extracted from rats and replaced with either CaCl2-HT implants (Ca-HT group),
      distilled water-HT implants (DW-HT group), or untreated implants (Cont group).
      After 4 weeks, the implant-PIE interface of the Ca-HT group exhibited a band of
      immunoreactive laminin-332, similar to the tooth-junctional epithelium interface,
      which was absent in the Cont and DW-HT groups at the upper portion. We also
      investigated the effect of Ca-HT on the attachment of rat oral epithelial cells
      (OECs). OEC adherence onto Ca-HT Ti plates was stronger with higher expression
      levels of adhesion proteins compared with Cont and DW-HT groups. These results
      indicate that HT with CaCl2 improves the integration of soft tissue cells with
      the Ti implant at 4 weeks after implantation, which might facilitate the
      development of a soft tissue barrier around the implant. 

PMID- 25982318
TI  - Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on
      ultrasmall MnO nanoparticles.
AB  - Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI)
      contrast agent in clinical diagnosis, but generally induces the risk of
      nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III)
      chelates. To develop a novel positive MRI contrast agent with low toxicity and
      high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn
      chelation and conjugated with cRGD as active targeting function to tumor.
      Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by
      alpha,beta-poly(aspartic acid)-based graft polymer containing PEG and DOPA
      moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with
      a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such
      nanoscaled contrast agent integrated passive- and active-targeting function to
      tumor, and its efficient accumulation behavior in tumor was verified by in vivo
      distribution study. At the same time, the PEG moiety played a role of hydrophilic
      coating to improve the biocompatibility and stability under storing and
      physiological conditions, and especially might guarantee enough circulation time
      in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing
      MRI signal for as-fabricated contrast agent while cell viability assay proved its
      acceptable cytotoxicity for MRI application. On the whole, the as-fabricated
      PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO
      nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor.

PMID- 25982320
TI  - Intravenous IgG (IVIG) and subcutaneous IgG (SCIG) preparations have comparable
      inhibitory effect on T cell activation, which is not dependent on IgG
      sialylation, monocytes or B cells.
AB  - IVIG modulates T cell activation in vitro and inflammatory-autoimmune conditions
      in vivo. Sialylation of IgG, Fc receptor interactions, modulation of
      monocyte/macrophage/B cell functions have been implicated in IVIG effects.
      Subcutaneous IgG (SCIG) therapy is increasingly used for IgG replacement but
      whether these preparations share the effects of IVIG on T cell modulation is not
      documented. We compared the potency of SCIG-HizentraTM (20% IgG preparation) with
      IVIG-Privigen(r) (10% IgG) for T cell inhibition, and assessed the involvement of
      IgG sialylation, monocytes and B cells in this process. Human PBMCs or sorted
      cells were cultured 3-7 days, and T cells were stimulated with immobilized anti
      CD3 mAb or Candida antigen. Thymidine incorporation into DNA was quantitated and
      cytokines assayed by ELISA/Luminex(r) assay. IVIG and SCIG both dose-dependently
      (1-20mg/ml) inhibited (up to >80%) T cell proliferation to anti-CD3 mAb. Response
      to Candida albicans was comparably inhibited by IVIG and SCIG by 50-80% at
      10mg/ml with inhibition even at 3mg/ml (P<0.05). These effects were not affected
      by depletion of sialic acid containing IgG using neuraminidase treatment or
      lectin affinity chromatography. With anti-CD3 or Candida stimulation, IL-1beta,
      IL-2, IL-5, IL-6, IL-13, GMCSF, TNF-alpha, interferon-gamma (with anti-CD3) and
      IL-17 (with Candida) levels were suppressed by IVIG or SCIG, with no effect on IL
      4, IL-10, IL-12, IL-15 or TGFbeta. Monocytes or B cells were not required for IgG
      induced suppression of proliferation, in fact depletion of monocytes potentiated
      the IgG-induced inhibition. Reconstitution with monocytes restored the original
      inhibitory effect. These data show that IVIG (Privigen(r)) and SCIG (HizentraTM)
      have comparable inhibitory effects on T cell activation, which do not require
      sialylation of IgG. Inhibition is independent of monocytes or B cells. There is a
      potent suppression of multiple effector cytokines. Like IVIG, SCIG therapy is
      expected to show immunomodulatory activity.

PMID- 25982319
TI  - Peptide ligand structure and I-Aq binding avidity influence T cell signaling
      pathway utilization.
AB  - Factors that drive T cells to signal through differing pathways remain unclear.
      We have shown that an altered peptide ligand (A9) activates T cells to utilize an
      alternate signaling pathway which is dependent upon FcRgamma and Syk. However, it
      remains unknown whether the affinity of peptide binding to MHC drives this
      selection. To answer this question we developed a panel of peptides designed so
      that amino acids interacting with the p6 and p9 predicted MHC binding pockets
      were altered. Analogs were tested for binding to I-A(q) using a competitive
      binding assay and selected analogs were administered to arthritic mice. Using the
      collagen-induced arthritis (CIA) model, arthritis severity was correlated with T
      cell cytokine production and molecular T cell signaling responses. We establish
      that reduced affinity of interaction with the MHC correlates with T cell
      signaling through the alternative pathway, leading ultimately to secretion of
      suppressive cytokines and attenuation of arthritis. 

PMID- 25982321
TI  - Endoliths in Lithophaga lithophaga shells--Variation in intensity of infestation
      and species occurrence.
AB  - Pronounced differences with respect to the extent of infestation and the degree
      of Lithophaga lithophaga shell damage inflicted by euendolithic taxa at two sites
      in the Adriatic Sea representing different productivity conditions, are
      described. Shells collected from the eastern part of Kastela Bay, which is
      characterized by higher primary productivity, have significantly more shell
      damage then the shell collected from a site on the outer coast of the island of
      Ciovo exposed to the oligotrophic Adriatic Sea. The presence of endoliths and
      their perforations were detected in different layers of the shell, including
      solidly mineralized parts of the skeleton and within the organic lamellae
      incorporated into the shell. Phototrophic endoliths were not observed in the
      specimens. The most serious damage to L. lithophaga shells was the boring
      clionaid sponge Pione vastifica, which was more common in shells collected from
      Kastela. 

PMID- 25982322
TI  - Association between NR4A2 genetic variation and schizophrenia: A comprehensive
      systematic review and meta-analysis.
AB  - The homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation
      has been implicated as a risk factor for schizophrenia (SZ). Nevertheless, the
      results are inconclusive. We conducted a comprehensive systematic review and meta
      analysis to quantify the impact of NR4A2 variation on the risk of SZ. All
      eligible case-control studies published up to September 2014 were identified by
      searching PubMed OVID, EBSCO, PsycINFO and ISI web of knowledge. Pooled odds
      ratio with 95% confidence interval were used to access the strength of
      association in fixed- or random-effects model. Seven studies that reported 17
      variants with a total of 3027 participants were included. Of these variants, five
      ones (rs143618355, rs199674295, c.366-369 del TAC, c.-469delG and P4) were
      present only in cases, and three ones (rs35479735, rs3832066 and rs397706674)
      were available for meta-analysis. Overall, there was no significant association
      between the three variants and SZ risk under allele model, dominant model and
      recessive model. The results failed to reveal significant link between NR4A2
      polymorphism and SZ risk. However, large-sized and well-designed studies are
      warranted to validate our findings. 

PMID- 25982323
TI  - Reduction of Nfia gene expression and subsequent target genes by binge alcohol in
      the fetal brain.
AB  - The objective of the present study was to investigate the changes in gene
      expression in the fetal brain (forebrain and hippocampus) caused by maternal
      binge alcohol consumption. Pregnant C57BL/6J mice were treated intragastrically
      with distilled phosphate-buffered saline (PBS) or ethanol (2.9 g/kg) from
      embryonic day (ED) 8-12. Microarray analysis revealed that a significant number
      of genes were altered at ED 18 in the developing brain. Specifically, in
      hippocampus, nuclear factor one alpha (Nfia) and three N-methyl-D-aspartate
      (Nmda) receptors (Nmdar1, Nmdar2b, and Nmdar2d) were down-regulated. The
      transcription factor Nfia controls gliogenesis, cell proliferation and Nmda
      induced neuronal survival by regulating the expression of target genes. Some of
      the Nfia-target gene (Aldh1a, Folh1, Gjb6, Fgf1, Neurod1, Sept4, and Ntsr2)
      expressions were also altered as expected. These results suggest that the altered
      expression of Nfia and Nmda receptors may be associated with the etiology of
      fetal alcohol syndrome (FAS). The data presented in this report will contribute
      to the understanding of the molecular mechanisms associated with the effects of
      alcohol in FASD individuals.

PMID- 25982324
TI  - Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of
      GABAergic interneurons in the spinal cord of neuropathic rats.
AB  - Although tianeptine, an atypical antidepressant has been reported to have
      antinociceptive effects, the mode of action is different from that of tricyclic
      antidepressants despite structural similarities. We examined the antiallodynic
      effect of intrathecal tianeptine in neuropathic pain rats and determined the
      involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic
      interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve
      ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5
      HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before
      delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on
      the activity of tianeptine. GAD expression and GABA concentrations were assessed.
      Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL
      rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect
      of tianeptine. Both GAD65 expression and the GABA concentration in the spinal
      cord were decreased in neuropathic rats but were increased by tianeptine.
      Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord.
      Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic
      interneurons together with GAD65 plays a role in the activity of tianeptine at
      the spinal cord level.

PMID- 25982325
TI  - Fronto-temporo-occipital activity changes with age during a visual working memory
      developmental study in children, adolescents and adults.
AB  - The present report analyzes differences in cerebral sources among several age
      groups with respect to the encoding, maintenance and recognition of stimuli
      during a visual working memory task. Differential intensity of involvement of
      anterior and posterior areas during working memory processing is expected at
      different ages. For that, 168 subjects between 6 and 26 years old performed a
      visual delayed match-to-sample task. The sample was subdivided into 5 age groups,
      and the cerebral sources were analyzed with sLORETA, comparing the groups two-by
      two. The results showed that at younger ages more posterior regions are involved
      in working memory processing, while in adulthood more anterior regions are
      involved. Maintaining the visual item in memory showed some common activated
      areas with stimulus matching, indicating similar neural mechanisms involved in
      holding and selecting the target stimulus. 

PMID- 25982326
TI  - Altered glycaemia differentially modulates efflux transporter expression and
      activity in hCMEC/D3 cell line.
AB  - The unique phenotype of blood-brain barrier (BBB) endothelium is partly
      maintained by abundant expression of ATP-binding cassette superfamily of efflux
      transporters that strictly restrict the CNS access to toxic substances including
      xenobiotics in circulation. Previously, we have shown that diabetes-related
      altered glycemic conditions differentially affect and compromise BBB integrity.
      However, the impact of diabetes on BBB efflux transporters is less understood. In
      this study, we examined the effects of single or repeated episodes of hypo-and
      hyperglycemia on major BBB efflux transporters expression/function in human
      cerebromicrovascular endothelial cell line (hCMEC/D3). Cells were exposed to
      normal (5.5 mM), hypo (2.2 mM) or hyper (25 or 35 mM)-glycemic media containing D
      glucose for 12h (acute) or two 3h episodes/day of hypo- or hyperglycemia with an
      intercalated 2h normalglycemic exposure for 3 days ("glycemic variability", see
      Methods). Acute hypoglycemic exposure (12h) up-regulated BBB endothelial mRNA and
      protein expression of P-glycoprotein, BCRP and other multidrug resistance
      associated proteins (MRP1 and 4) paralleled by an increase in transporter
      specific efflux activity (~ 2-fold vs. control). Although, 12h hyperglycemia did
      not affect the efflux transporter expression (except for MRP4), a significant
      increase in BCRP activity was observed. By contrast, DNA microarray data revealed
      that repeated hyperglycemic episodes (but not hypoglycemia) significantly up
      regulate P-glycoprotein expression and activity. Thus, this study suggests a
      differential impact of altered glycemic conditions on major BBB drug efflux
      transporters expression/function, sensitive to the length of exposure (acute vs.
      repeated), with an implication for altered CNS drug disposition in diabetic
      population.

PMID- 25982328
TI  - Immobilized photosensitizers for antimicrobial applications.
AB  - Photodynamic antimicrobial chemotherapy (PACT) is a very promising alternative to
      conventional antibiotics for the efficient inactivation of pathogenic
      microorganisms; this is due to the fact that it is virtually impossible for
      resistant strains to develop due to the mode of action employed. PACT employs a
      photosensitizer, which preferentially associates with the microorganism, and is
      then activated with non-thermal visible light of appropriate wavelength(s) to
      generate high localized concentrations of reactive oxygen species (ROS),
      inactivating the microorganism. The concept of using photosensitizers immobilized
      on a surface for this purpose is intended to address a range of economic,
      ecological and public health issues. Photosensitising molecules that have been
      immobilized on solid support for PACT applications are described herein.
      Different supports have been analyzed as well as the target microorganism and the
      effectiveness of particular combinations of support and photosensitizer. 

PMID- 25982329
TI  - Benzaldehyde Schiff bases regulation to the metabolism, hemolysis, and virulence
      genes expression in vitro and their structure-microbicidal activity relationship.
AB  - There is an urgent need to develop new antibacterial agents because of multidrug
      resistance by bacteria and fungi. Schiff bases (aldehyde or ketone-like
      compounds) exhibit intense antibacterial characteristics, and are therefore,
      promising candidates as antibacterial agents. To investigate the mechanism of
      action of newly designed benzaldehyde Schiff bases, a series of high-yielding
      benzaldehyde Schiff bases were synthesized, and their structures were determined
      by NMR and MS spectra data. The structure-microbicidal activity relationship of
      derivatives was investigated, and the antibacterial mechanisms were investigated
      by gene assays for the expression of functional genes in vitro using Escherichia
      coli, Staphylococcus aureus, and Bacillus subtilis. The active compounds were
      selective for certain active groups. The polar substitution of the R2 group of
      the amino acids in the Schiff bases, affected the antibacterial activity against
      E. coli and S. aureus; specific active group at the R3 or R4 groups of the
      acylhydrazone Schiff bases could improve their inhibitory activity against these
      three tested organisms. The antibacterial mechanism of the active benzaldehyde
      Schiff bases appeared to regulate the expression of metabolism-associated genes
      in E. coli, hemolysis-associated genes in B. subtilis, and key virulence genes in
      S. aureus. Some benzaldehyde Schiff bases were bactericidal to all the three
      strains and appeared to regulate gene expression associated with metabolism,
      hemolysis, and virulence, in vitro. The newly designed benzaldehyde Schiff bases
      possessed unique antibacterial activity and might be potentially useful for
      prophylactic or therapeutic intervention of bacterial infections. 

PMID- 25982327
TI  - How to routinely collect data on patient-reported outcome and experience measures
      in renal registries in Europe: an expert consensus meeting.
AB  - Despite the potential for patient-reported outcome measures (PROMs) and
      experience measures (PREMs) to enhance understanding of patient experiences and
      outcomes they have not, to date, been widely incorporated into renal registry
      datasets. This report summarizes the main points learned from an ERA-EDTA QUEST
      funded consensus meeting on how to routinely collect PROMs and PREMs in renal
      registries in Europe. In preparation for the meeting, we surveyed all European
      renal registries to establish current or planned efforts to collect PROMs/PREMs.
      A systematic review of the literature was performed. Publications reporting
      barriers and/or facilitators to PROMs/PREMs collection by registries were
      identified and a narrative synthesis undertaken. A group of renal registry
      representatives, PROMs/PREMs experts and patient representatives then met to (i)
      share any experience renal registries in Europe have in this area; (ii) establish
      how patient-reported data might be collected by understanding how registries
      currently collect routine data and how patient-reported data is collected in
      other settings; (iii) harmonize the future collection of patient-reported data by
      renal registries in Europe by agreeing upon preferred instruments and (iv) to
      identify the barriers to routine collection of patient-reported data in renal
      registries in Europe. In total, 23 of the 45 European renal registries responded
      to the survey. Two reported experience in collecting PROMs and three stated that
      they were actively exploring ways to do so. The systematic review identified 157
      potentially relevant articles of which 9 met the inclusion criteria and were
      analysed for barriers and facilitators to routine PROM/PREM collection. Thirteen
      themes were identified and mapped to a three-stage framework around establishing
      the need, setting up and maintaining the routine collection of PROMs/PREMs. At
      the consensus meeting some PROMs instruments were agreed for routine renal
      registry collection (the generic SF-12, the disease-specific KDQOLTM-36 and EQ-5D
      5L to be able to derive quality-adjusted life years), but further work was felt
      to be needed before recommending PREMs. Routinely collecting PROMs and PREMs in
      renal registries is important if we are to better understand what matters to
      patients but it is likely to be challenging; close international collaboration
      will be beneficial.

PMID- 25982330
TI  - Novel water soluble neutral vanadium(IV)-antibiotic complex: Antioxidant,
      immunomodulatory and molecular docking studies.
AB  - A novel water soluble five coordinate oxovanadium(IV) complex,
      [VO(C16H15N4O8S)HSO4] incorporating cefuroxime, a cephalosporin group of
      antibiotic have been prepared from an interaction of vanadyl sulfate and
      cefuroxime in aqueous solution. The compound was characterized by Fourier
      transform infrared spectroscopy (FTIR), CHN microanalyses, ultraviolet-visible
      spectroscopy (UV-Vis), fast atom bombardment (FAB) mass spectrometry and
      thermogravimetric analysis (TGA). Density Functional Theory (DFT) computation
      using Gaussian 09 program at B3LYP level revealed a distorted square pyramidal
      energy optimized geometry for the vanadyl(IV) complex. The molecular docking
      studies show that the interaction between the vanadium complex and protein
      receptor, clathrin is dominated by hydrophobic forces. The experimental (1)H
      nuclear magnetic resonance (NMR) features of the analogous Zn(II) complex matched
      well with the theoretically computed values further affirming the distorted
      square pyramidal geometry for the vanadyl(IV) complex. Cyclic voltammetry
      revealed a metal centered single-electron oxidation-reduction response for
      VO(IV)/VO(V) couple. The antioxidant activity of the vanadium(IV)-complex vis-a
      vis the antibiotic has been assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      method. The vanadium complex showed comparatively better radical scavenging
      ability compared to the antibiotic cefuroxime. The antimicrobial activity of the
      compound has been assayed for five different microbial strains using minimum
      inhibitory concentration (MIC) method. Immunomodulatory studies carried out using
      phagocytosis index, myeloperoxidase release and cytokine assay indicated the
      vanadium(IV)-complex to be immunosuppressant. The cytotoxicity of the compound
      was evaluated by MTT (3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium
      bromide) reduction assay. 

PMID- 25982331
TI  - Synthesis, and structure-activity relationship for C(4) and/or C(5) thienyl
      substituted pyrimidines, as a new family of antimycobacterial compounds.
AB  - Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution
      of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis
      of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from
      commercially available 5-bromopyrimidine. All new pyrimidines were found to be
      active in micromolar concentrations in vitro against H37Rv, avium, terrae,
      rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The
      data for acute in vivo toxicity in mice have been obtained for these compounds
      which appear to be promising antitubercular agents. 

PMID- 25982332
TI  - A transgenic mouse model for the in vivo bioluminescence imaging of the
      expression of the lysophosphatidic acid receptor 3: relevance for inflammation
      and uterine physiology research.
AB  - Lysophosphatidic acid (LPA) is a lipid-derived signaling molecule that plays key
      roles in diverse biological processes including inflammation and uterine
      remodeling. Although the function of LPA and its receptors has been extensively
      studied using knock-out mice, the temporal-spatial expression of LPA receptors is
      less well-characterized. To gain further insight into the dynamic regulation of
      LPA receptor 3 (Lpar3) expression in vivo by bioluminescence imaging, we
      generated and characterized mice transgenic for a putative Lpar3 promoter
      fragment. A non-coding region of the Lpar3 gene immediately upstream of the start
      site was subcloned adjacent to the luciferase gene. Promoter activity was
      determined by in vitro luciferase assays, in vivo bioluminescent imaging or by
      semi-quantitative real-time PCR. The air-pouch model was used to investigate
      Lpar3 promoter activity in the context of inflammation. The putative Lpar3
      promoter fragment behaved similarly to the endogenous promoter in vitro and in
      vivo. In male mice, elevated levels of Lpar3-induced luciferase activity were
      observed in the testis. In female mice, the basal level of luciferase activity in
      the uterus significantly increased during pseudopregnancy. Moreover, luciferase
      activity was upregulated by TNF-alpha in the air-pouch model. We report the
      identification of a functional Lpar3 promoter fragment and the generation of a
      transgenic mouse model to investigate the regulation of Lpar3 promoter activity
      non-invasively in vivo by bioluminescence imaging. This mouse model is a valuable
      tool for reproductive biology and inflammation research as well as other
      biological processes in which this receptor is involved. 

PMID- 25982333
TI  - Placental claudin expression and its regulation by endogenous sex steroid
      hormones.
AB  - Tight junctions (TJs) form continuous intercellular contacts controlling the
      paracellular transportation across the cell-to-cell junction. TJ components
      include the peripheral protein zonula occludens-1 (ZO-1), junctional adhesion
      molecules (JAMs), and integral proteins such as occludin and claudins. Among the
      junction proteins, claudins play a major role in regulation of paracellular
      electrolyte transportation. This study explores the expression and distribution
      of tight junctions and their regulation during pregnancy. To study the regulation
      of claudin family, we examined expression of mouse placental tight junction
      proteins, including claudin-1 to -24, with real-time PCR and Western blotting and
      distribution of tight junction proteins with immunohistochemistry. Pregnant
      C57/BL6 mice were used in this study. The pregnant mice were divided into three
      groups depending on pregnant day (on days 12, 16, and 20 of gestation). Regarding
      the transcription levels, claudin-1, claudin-2, claudin-4, and claudin-5
      expression levels were relatively high compared to other claudin family in all
      periods of pregnancy. Claudin-4 and 5 expressions, which reduce ion permeability,
      were increased over a period of time. However, claudin-2 expression, that is the
      responsive protein for a decrease in paracellular conductance, was decreased.
      Following this modulation of expression during mid-term pregnancy, we identified
      endogenous hormonal modulation of claudin family using estrogen receptor
      antagonist ICI 182,780 and progesterone receptor antagonist RU-486. After
      administration of ICI and RU-486, expression of claudin-4 mRNA and protein was
      increased. In addition, immunohistochemistry was performed to identify their
      localization for inferring permeability in placenta. Due to the function of
      claudins as effectors of ion transport at the end of regulatory pathways, they
      must be transducing proteins that modulate the function of claudins and thus link
      the physiologic inputs to the final effectors. This study will provide the
      claudin expressions and their localization in the mouse placenta, and their
      regulation by endogenous hormones. Taken together, the results of this study may
      contribute to assuming the roles and regulatory mechanism of these tight junction
      genes regarding maternal-fetal ion transportation in the placenta. 

PMID- 25982334
TI  - Engaging in research: challenges and opportunities for health library and
      information professionals.
AB  - This year's virtual issue (the 6th in the series) has been published to coincide
      with the European Association for Health Information and Libraries' (EAHIL) 2015
      workshop (10-12 June, Edinburgh): Research-Minded: Understanding, Supporting,
      Conducting Research. This event is being run in collaboration with the
      International Conference of Animal Health Information Specialists and the
      International Clinical Librarian Conference. Although research has always been a
      central part of any librarian's role, until recently health librarians and
      library users and funding bodies assumed that librarians were 'midwives' - there
      to assist students, clinicians, academics and managers set up and carry out their
      research. The notion of the librarian as a professional with a research agenda,
      who understands research methods, submits research grants, and publishes, is a
      relatively new perspective. If librarians are to take an evidence-based approach
      to their profession they need to acquire research skills. This is the rationale
      for the 2015 EAHIL workshop. To support the workshop, this virtual issue contains
      six original articles published in Health Information and Libraries Journal over
      the last 2 years that demonstrate the range of research activities carried out by
      health librarians, as well as a review article and articles from each of the
      three feature columns. All articles included in this virtual issue are available
      free online.

PMID- 25982335
TI  - Erratum to: The Contribution of the Cerebellum in the Hierarchial Development of
      the Self.

PMID- 25982336
TI  - Correction of concealed penis with preservation of the prepuce.
AB  - INTRODUCTION: By definition, congenital concealed penis presents at birth.
      Children are usually referred to physicians because of parental anxiety caused by
      their child's penile size. OBJECTIVE: Several surgical procedures have been
      described to treat this condition, but its correction is still technically
      challenging. The present study reports a simple surgical approach, which allows
      preservation of the prepuce. PATIENTS AND METHODS: During the last 6 years, 18
      children with concealed penis (according to the classification by Maizels et al.)
      have been treated in the present department (mean age 4.5 years, range 3-12
      years). Patients with other conditions that caused buried penis were excluded
      from the study. The operation was performed through a longitudinal midline
      ventral incision, which was extended hemi-circumferentially at the penile base.
      The dysgenetic dartos was identified and its distal part was resected. Dissection
      of the corpora cavernosa was carried down to the suspensory ligament, which was
      sectioned. Buck's fascia was fixed to Scarpa's fascia and shaft skin was
      approximated in the midline. Penoscrotal angle was fashioned by Z-plasty or V-Y
      plasty. RESULTS: The median follow-up was 24 months (range 8-36). The
      postoperative edema was mild and resolved within a week. All children had good to
      excellent outcomes. The median pre-operative to postoperative difference in
      penile length in the flaccid state was 2.6 cm (range 2.0-3.5). No serious
      complications or recurrent penile retraction were noted. DISCUSSION: Recent
      literature mostly suggests that concealed penis is due to deficient proximal
      attachments of dysgenetic dartos. Consequences of this include: difficulties in
      maintaining proper hygiene, balanitis, voiding difficulties with prepuce
      ballooning and urine spraying, and embarrassment among peers. Surgical treatment
      for congenital concealed penis is warranted in children aged 3 years or older.
      The basis of the technique is the perception that in boys with congenital
      concealed penis, the penile integuments are normal but they have abnormal
      attachments, and that incision of the skin and dartos will allow the shaft to
      extend. Furthermore, incisions of the fundiform and suspensory ligaments
      facilitate this maneuver. With this technique, the blood supply of the penile
      skin is not interrupted and postoperative lymphedema, a difficult complication to
      deal with, is prevented. One major advantage is the preservation of the prepuce,
      giving a normal penile appearance and an excellent cosmetic result. CONCLUSION:
      The method proposed here is simple and has no serious complications. It is
      suggested that this condition be treated in pre-school-aged children in order to
      prevent psychological impairment.

PMID- 25982337
TI  - Retroperitoneal laparoscopy management for ureteral fibroepithelial polyps
      causing hydronephrosis in children: a report of five cases.
AB  - INTRODUCTION: Hydronephrosis is a common disease in children and may be caused by
      ureteral fibroepithelial polyps (UFP). Ureteral fibroepithelial polyps are rare
      in children and are difficult to precisely diagnose before surgery. Surgical
      treatment for symptomatic UFP is recommended. At the present institution,
      retroperitoneal laparoscopy has been used to treat five boys with UFP since 2006.
      OBJECTIVE: To highlight the significance of UFP as an etiological factor of
      hydronephrosis in children and evaluate the applicative value of retroperitoneal
      laparoscopy in the treatment of children with UFP. METHODS: Between 2006 and 2013
      five boys underwent retroperitoneal laparoscopy at the present institution. They
      were identified with UFP by review of the clinical database. Detailed data were
      collected, including: radiographic studies, gross anatomical pathology, and
      pathology and radiology reports. All boys had been followed up at least every 6
      months. RESULTS: All of the boys were aged between 7 and 16 years (mean 9.8
      years). The main symptoms were flank pain (all five) and hematuria (three).
      Radiographic examination showed that all of the boys presented with incomplete
      ureteral obstruction and hydronephrosis. The ureteral fibroepithelial polyps were
      located near the left UPJ or the left proximal ureter. All of the boys had the
      UFP removed: three underwent retroperitoneal laparoscopic dismembered Anderson
      Hynes pyeloplasty and polypectomy, and two had retroperitoneal laparoscopic
      ureteral anastomosis. These polyps were all on the left side and between 15 and
      35 mm in length (mean 22 mm) (Figure). All of the boys recovered well and were
      discharged from hospital. The postoperative histological report confirmed that
      the specimens were UFP. Hydronephrosis was periodically assessed by
      ultrasonography (using the same method as pre-surgical ultrasonography) after
      surgery. Mean follow-up was 33 months (range 6-58 months) and no complications
      were found afterwards. CONCLUSIONS: Ureteral fibroepithelial polyps are rare but
      rather important as they can cause UPJ obstruction, which often manifests as
      hydronephrosis. It is most important to confirm the site of ureteral obstruction
      before surgery as this may have an effect on the surgical management. It is
      recommended that UFP be successfully managed in children with retroperitoneal
      laparoscopy.

PMID- 25982338
TI  - Therapeutic superiority of combined propranolol with short steroids course over
      propranolol monotherapy in infantile hemangioma.
AB  - Infantile hemangiomas are the most common benign childhood tumor that may have
      functional and/or cosmetic complications. We aimed to compare the clinical
      efficacy of propranolol alone and propranolol primed with systemic
      corticosteroids on the outcome of infantile hemangioma. A prospective randomized
      study included 40 infants aged less than 9 months with cutaneous hemangiomas.
      Patients were randomly assigned into two groups: group A were given oral
      prednisolone for the initial 2 weeks combined with oral propranolol, while group
      B were given oral propranolol alone for 6 months. The median age of the studied
      patients was 4.5 months (ranged 4 weeks-8 months). Sequential determination of
      the dimensions of the hemangiomas based on direct measurement and photographic
      analysis were performed. A significant reduction in the size of the lesions was
      found in group A in the 2-, 4-, and 8-week evaluation compared to group B (p <
      0.001) with no statistical difference in the ultimate 6 month response (p =
      0.134). Multiple logistic regression showed that early treatment before 6 months
      of age (OR 9.82, p = 0.007) and combined treatment with propranolol and
      prednisolone (OR 10.71, p = 0.006) were the predictors of best response.
      CONCLUSION: Combining propranolol with corticosteroids gives a faster response
      and should be considered in treating life- or function-threatening hemangiomas.

PMID- 25982339
TI  - Cancer susceptibility syndromes in children in the area of broad clinical use of
      massive parallel sequencing.
AB  - Children diagnosed with cancer are considered for inherited cancer susceptibility
      testing according to well-established clinical criteria. With increasing efforts
      to personalize cancer medicine, comprehensive genome analyses will find its way
      into daily clinical routine in pediatric oncology. Whole genome and exome
      sequencing unavoidably generates incidental findings. The somatic "molecular make
      up" of a tumor genome may suggest a germline mutation in a cancer susceptibility
      syndrome. At least two mechanisms are well-known, (a) chromothripsis (Li-Fraumeni
      syndrome) and (b) a high total number of mutational events which exceeds that of
      other samples of the same tumor type (defective DNA mismatch repair). Hence,
      pediatricians are faced with the fact that genetic events within the tumor genome
      itself can point toward underlying germline cancer susceptibility. Whenever
      genetic testing including next-generation sequencing (NGS) is initiated, the
      pediatrician has to inform about the benefits, risks, and alternatives, discuss
      the possibility of incidental findings and its disclosure, and to obtain informed
      consent prior to testing. CONCLUSIONS: Genetic testing and translational research
      in pediatric oncology can incidentally uncover an underlying cancer
      susceptibility syndrome with implications for the entire family. Pediatricians
      should therefore increase their awareness of chances and risks that accompany the
      increasingly wide clinical implementation of NGS platforms.

PMID- 25982342
TI  - Mapping the intriguing transient morphologies and the demixing behavior in
      PS/PVME blends in the presence of rod-like nanoparticles.
AB  - The demixing behavior, transient morphologies and mechanism of phase separation
      in PS/PVME blends were greatly altered in the presence of a very low
      concentration of rod-like particles (multiwall carbon nanotubes, MWNTs). This
      phenomenon is due to the specific interaction of one of the phases (PVME) with
      the anisotropic MWNTs, which creates a heterogeneous environment in the blend.
      This specific interaction alters the chain dynamics in the interfacial region as
      against the bulk. A comprehensive analysis using isochronal temperature sweep was
      performed to understand the demixing temperature in the blends. The evolution of
      phase morphology as a function of time and temperature was assessed by polarizing
      optical microscopy (POM), atomic force microscopy (AFM) and scanning electron
      microscopy (SEM). The addition of MWNTs increased the rheological demixing
      temperature and the spinodal temperature in almost all the compositions. The
      intriguing transient morphologies were mapped, which varied from nucleation and
      growth to coalescence-induced viscoelastic phase separation (C-VPS) in PVME-rich
      blends, to spinodal decomposition in the near-critical compositions, to transient
      gel-induced VPS (T-VPS) in the PS-rich compositions. Mapping of the morphology
      development displayed two types of fracture mechanisms: ductile fracture for near
      critical compositions and brittle fracture for off-critical composition. The
      change in the phase separation mechanism in the presence of MWNTs was due to the
      variation in dynamic asymmetry brought about by these anisotropic particles. All
      these observations were correlated by POM, SEM and AFM studies. The length of the
      cooperatively rearranging region (CRR), as evaluated using modulated differential
      scanning calorimetry (MDSC) measurements, was found to be composition
      independent. The observed variation of effective glass transition of PVME (low Tg
      component) on blending with PS (high Tg component) and by the addition of MWNTs
      accounts for the dynamic heterogeneity introduced by MWNTs in the system. 

PMID- 25982341
TI  - Food and fluid texture consumption in a population-based cohort of preschool
      children with cerebral palsy: relationship to dietary intake.
AB  - AIM: To determine the texture constitution of children's diets and its
      relationship to oropharyngeal dysphagia (OPD), dietary intake, and gross motor
      function in young children with cerebral palsy (CP). METHOD: A cross-sectional,
      population-based cohort study comprising 99 young children with CP (65 males, 35
      females) aged 18 to 36 months (mean age 27mo; Gross Motor Function Classification
      System [GMFCS] level I, n=45; II, n=13; III, n=14; IV, n=10; V, n=17). CP
      subtypes were classified as spastic unilateral (n=35), spastic bilateral (n=49),
      dyskinetic (n=5), and other (n=10), in accordance with the criteria of the
      Surveillance of Cerebral Palsy in Europe. Habitual dietary intake of food
      textures, energy, and water were determined from parent-completed 3-day weighed
      food records. Parent-reported feeding ability of food textures was reported on
      the Pediatric Evaluation of Disability Inventory and a feeding questionnaire. OPD
      was classified based on clinical feeding assessment using the Dysphagia Disorders
      Survey (rated by a certified assessor, KAB) and a subjective Swallowing Safety
      Recommendation (classified by a paediatric speech pathologist, KAB). RESULTS:
      Food/fluid textures were modified for 39% of children. Children with poorer gross
      motor function tended to receive a greater proportion of energy from fluids
      (GMFCS levels IV-V: beta=0.9, p=0.002) in their diets and fewer chewable foods
      (level III: beta=-0.7, p=0.03; levels IV-V: beta=-1.8, p<0.001) compared to level
      I to II participants. Fluids represented a texture for which children frequently
      had OPD and the texture most frequently identified as unsafe (or recommended for
      instrumental assessment). INTERPRETATION: These findings indicate that swallowing
      safety, feeding efficiency, and energy/water intake should be considered when
      providing feeding recommendations for children with CP.

PMID- 25982340
TI  - Comparison of epidemiology and clinical characteristics of infections by human
      parechovirus vs. those by enterovirus during the first month of life.
AB  - Human parechoviruses (HPeV) have been recently recognized as important viral
      agents in paediatric infections. The aims of this study were to investigate the
      HPeV infection prevalence in infants <1 month in Spain and, secondly, to analyse
      the clinical and epidemiological characteristics of the infected patients
      compared with those infected by enterovirus (EV). Infants <1 month with
      neurological or systemic symptoms were included in a multicentre prospective
      study. EV and HPeV detection by RT-PCR and genotyping were performed in
      cerebrospinal fluids (CSF), sera or throat swabs. Out of the total of 84 infants
      studied during 2013, 32 were EV positive (38 %) and 9 HPeV positive (11 %). HPeV
      3 was identified in eight cases and HPeV-5 in one. Mean age of HPeV-positive
      patients was 18 days. Diagnoses were fever without source (FWS) (67 %), clinical
      sepsis (22 %) and encephalitis (11 %). Leukocytes in blood and CSF were normal.
      Pleocytosis (p = 0.03) and meningitis (p = 0.001) were significantly more
      frequent in patients with EV infections than with HPeV. CONCLUSIONS: Although
      HPeV-3 infections were detected less frequently than EV, they still account for
      approximately 10 % of the cases analysed in infants younger than 1 month. HPeV-3
      was mainly associated with FWS and without leukocytosis and pleocytosis in CSF.
      In these cases, HPeV screening is desirable to identify the aetiologic agent and
      prevent unnecessary treatment and prolonged hospitalization.

PMID- 25982343
TI  - Rapid HIV test in family practice.
AB  - BACKGROUND: The 2010-2014 HIV/AIDS French program recommends using HIV rapid
      diagnostic tests in family practice. Our aim was to assess the acceptability and
      feasibility of the RDT in family practice in France. METHODS: The first part of
      this study was to determine the opinions of family practitioners (FPs) concerning
      the news guidelines for screening and the possible use of rapid HIV tests in
      their practice. The second part was a feasibility study of the actual use of
      rapid HIV tests given to FPs during six months. The third part was a qualitative
      analysis of experience feedback to determine the impediments to using rapid HIV
      tests. RESULTS: Seventy-seven percent of the 352 FPs interviewed were favorable
      to rapid HIV tests use. The three main impediments were: misinterpretation of
      test result, complexity of quality control, and lack of training: 23 of the 112
      FPs having volunteered to evaluate the rapid HIV tests followed the required
      training session. Sixty-nine tests were handed out, and three rapid HIV tests
      were used; the qualitative study involved 12 FPs. The participants all agreed on
      the difficult use of rapid HIV tests in daily practice. The main reasons were:
      too few opportunities or requests for use, complex handling, difficulties in
      proposing the test, fear of having to announce seropositivity, significantly
      longer consultation. CONCLUSION: Although FPs are generally favorable to rapid
      HIV tests use in daily practice, the feasibility and contribution of rapid HIV
      tests are limited in family practice.

PMID- 25982344
TI  - Facile synthesis of acridines via Pd(0)-diphosphine complex-catalyzed tandem
      coupling/cyclization protocol.
AB  - A facile and efficient approach for the synthesis of a variety of acridines via
      the tandem coupling/cyclization of substituted 2-bromobenzaldehydes and anilines
      is described. The reaction can be accomplished with ease in the presence of a
      catalytic amount of Pd2(dba)3 and diphosphine ligand dppf, providing a broad
      range of substituted acridines in good to excellent yields (up to 99%). The Lewis
      acid, AlCl3, is required to promote the cyclization for less electron-rich
      anilines. 

PMID- 25982345
TI  - Reply to letter to the editor concerning: Regulation of testicular descent.

PMID- 25982346
TI  - Structures of the metallic and superconducting high pressure phases of solid CS2.
AB  - First principles structural prediction and molecular dynamics (MD) calculations
      have been performed to examine the structures responsible for the recently
      reported metallic and superconducting phases of highly compressed CS2. The low
      pressure experimental molecular crystal structure was found to be metastable and
      transformed into a disordered structure above 10 GPa. At 60 GPa, the predicted
      low energy structures show molecular CS2 is separated into C and S dominant
      regions. A crystalline structure with the P21/m symmetry was found to be most
      stable from 60 to 120 GPa. The structure is formed from alternate layers of
      hexagonal C rings and S 2D-square-nets linked by C-S bonds. A non-crystalline
      structure with similar features structure is also predicted by MD calculations.
      Electron-phonon coupling calculations show this crystalline phase is
      superconductive. Contrary to the suggestions made from the experiments, no
      magnetism was found in all predicted low enthalpy high pressure structures.
      Moreover, the theoretical results do not support the proposal on the existence of
      hypervalent 6-coordinated carbon at 120 GPa.

PMID- 25982347
TI  - LC-MS-based metabolite profiling of methanolic extracts from the medicinal and
      aromatic species Mentha pulegium and Origanum majorana.
AB  - INTRODUCTION: There has been increasing interest dedicated to the phenolic
      compounds with a view to their antioxidant and healthy properties. Recent studies
      have focused on plants from the Lamiaceae family with special interest in
      phenolic compounds antioxidant potential. OBJECTIVE: The metabolite profile of
      methanolic extracts from two Lamiacea medicinal plants was investigated.
      MATERIALS AND METHODS: Mentha pulegium and Origanum majorana methanolic extracts
      were analysed using reversed-phase ultra-high-performance liquid chromatography
      (RP-UHPLC) coupled to electrospray ionisation quadrupole time-of-flight mass
      spectrometry (ESI-QTOF-MS) detection in the negative ion mode. RESULTS: A total
      of 85 metabolites were characterised from different families, such as organic
      acids and derivatives, amino acids and derivatives, nucleosides, phenolic
      compounds as well as other polar metabolites, by using the MS and MS/MS
      information provided by the QTOF-MS. However, the total phenols and flavonoids
      were also quantified spectrophotometrically and they registered higher amounts in
      Mentha pulegium than in Origanum majorana extract. Gallocatechin was the major
      compound in M. pulegium extract whereas quercetin dimethyl ether, jaceidin and
      dihydrokaempferide were the major ones in O. majorana extract. CONCLUSION: The
      distribution of phenolic compounds in the methanolic extract showed a variation
      among studied plants. Mentha pulegium can be considered as a source of
      gallocatechin.

PMID- 25982349
TI  - Researchers identify mutations in familial pulmonary fibrosis.

PMID- 25982350
TI  - Calcium-sensing receptors linked to development of asthma.

PMID- 25982348
TI  - Quantification of atrial dynamics using cardiovascular magnetic resonance: inter
      study reproducibility.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) offers quantification of
      phasic atrial functions based on volumetric assessment and more recently, on CMR
      feature tracking (CMR-FT) quantitative strain and strain rate (SR) deformation
      imaging. Inter-study reproducibility is a key requirement for longitudinal
      studies but has not been defined for CMR-based quantification of left atrial (LA)
      and right atrial (RA) dynamics. METHODS: Long-axis 2- and 4-chamber cine images
      were acquired at 9:00 (Exam A), 9:30 (Exam B) and 14:00 (Exam C) in 16 healthy
      volunteers. LA and RA reservoir, conduit and contractile booster pump functions
      were quantified by volumetric indexes as derived from fractional volume changes
      and by strain and SR as derived from CMR-FT. Exam A and B were compared to assess
      the inter-study reproducibility. Morning and afternoon scans were compared to
      address possible diurnal variation of atrial function. RESULTS: Inter-study
      reproducibility was within acceptable limits for all LA and RA volumetric, strain
      and SR parameters. Inter-study reproducibility was better for volumetric indexes
      and strain than for SR parameters and better for LA than for RA dynamics. For the
      LA, reservoir function showed the best reproducibility (intraclass correlation
      coefficient (ICC) 0.94-0.97, coefficient of variation (CoV) 4.5-8.2%), followed
      by conduit (ICC 0.78-0.97, CoV 8.2-18.5%) and booster pump function (ICC 0.71
      0.95, CoV 18.3-22.7). Similarly, for the RA, reproducibility was best for
      reservoir function (ICC 0.76-0.96, CoV 7.5-24.0%) followed by conduit (ICC 0.67
      0.91, CoV 13.9-35.9) and booster pump function (ICC 0.73-0.90, CoV 19.4-32.3).
      Atrial dynamics were not measurably affected by diurnal variation between morning
      and afternoon scans. CONCLUSIONS: Inter-study reproducibility for CMR-based
      derivation of LA and RA functions is acceptable using either volumetric, strain
      or SR parameters with LA function showing higher reproducibility than RA function
      assessment. Amongst the different functional components, reservoir function is
      most reproducibly assessed by either technique followed by conduit and booster
      pump function, which needs to be considered in future longitudinal research
      studies.

PMID- 25982352
TI  - Bioinformatics drives the applications of next-generation sequencing in
      translational biomedical research.

PMID- 25982351
TI  - Incidence and early outcomes associated with pre-transplant antivimentin
      antibodies in the cardiac transplantation population.
AB  - BACKGROUND: In cardiac transplant recipients, the development of antibodies to
      the endothelial intermediate filament protein vimentin (antivimentin antibodies,
      AVA) has been associated with rejection and poor outcomes. However, the incidence
      of these antibodies prior to transplantation and their association with early
      rejection has not been investigated. METHODS: Pre-transplant serum was analyzed
      from 50 patients who underwent de novo cardiac transplant at Johns Hopkins
      Hospital from 2004 to 2012. Demographic, one-yr rejection, and survival data were
      obtained from the transplant database. RESULTS: The incidence of pre-transplant
      AVA was 34%. AVA-positive patients were younger (p = 0.03), and there was an a
      trend toward incidence in females (p = 0.08). Demographic data were similar among
      both groups. AVA positivity did not predict rejection in the first year post
      transplant. There was no difference in rejection-free graft survival (53 vs. 52%,
      p = 0.85) at one yr. Similarly, there was no difference in graft survival at one
      yr (82 vs. 88%, p = 0.56) or graft survival at a median follow-up of 23 and 26
      months, respectively (76 vs. 85%, p = 0.41). CONCLUSIONS: AVA is common in the
      cardiac pre-transplant population with a higher incidence in the young. The
      presence of detectable AVA did not correlate with early post-transplant rejection
      or graft survival.

PMID- 25982354
TI  - Do ultrasound findings of levator ani "avulsion" correlate with anatomical
      findings: A multicenter cadaveric study.
AB  - AIMS: This study aimed to validate the levator "avulsion" injury as seen on
      ultrasound against anatomical dissection in the same cadaver. METHODS:
      Puboviseral muscle (PVM) anatomy of female cadavers was studied using 3D
      translabial ultrasonography and an "avulsion" confirmed per standard
      recommendations [Dietz HP. Aust N Z J Obstet Gynaecol 53:220-230, 2013]. Cadavers
      were then dissected to determine the macroscopic attachment or detachment of the
      PVM and the dimensions including the PVM symphysis gap and PVM attachment depth.
      Intra and inter-observer reliability of USS findings and anatomical measurements
      were assessed using the Cohen's kappa and Bland & Altman plots respectively.
      McNemar's and Mann-Whitney U tests were used to compare imaging and cadaveric
      dissection findings. RESULTS: "Avulsions" were seen on imaging in 11/30 (36.7%)
      cadavers; the defect was bilateral in 1/30 (3.3%) and unilateral in 10/30
      (33.3%). No "avulsion" was found at dissection (McNemar's chi(2)  = 60.0, P <
      0.001). An additional thirty-nine cadavers were dissected with no "avulsion"
      identified. A narrower PVM insertion depth was strongly associated with
      "avulsion" on ultrasound (mean: 4.79 mm vs. 6.32 mm, Z = -3.191, P = 0.001).
      Intra- and inter-observer agreement was perfect (K = 1.0 +/- 0.0) and good (K =
      0.85 +/- 0.142) for anatomical "avulsions" and USS, respectively. CONCLUSIONS:
      There is a clear difference between anatomical and USS findings. The imaged
      appearance of an "avulsion" does not represent a true anatomical "avulsion" as
      confirmed on dissection. The term "avulsion" is misrepresentative and should not
      be used to describe this imaging finding. Moreover, further attempts at
      surgically repairing this defect should be avoided, at least until there is a
      better understanding of its pathophysiology. Neurourol. Urodynam 35:683-688,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25982353
TI  - Two cases of sporotrichosis of the right upper extremity in right-handed patients
      with diabetes mellitus.
AB  - BACKGROUND: Sporothrix species have proved to show high degrees of endemicity.
      Sporothrix globosa is the only pathogenic Sporothrix species that has till date
      been reported from China, where it is endemic in the northeastern provinces.
      AIMS: We report two cases of lymphocutaneous sporotrichosis with diabetes
      mellitus as underlying disease in patients from the non-endemic area of China.
      METHODS: A 59-year-old farmer and a 60-year-old gardener were admitted in
      February and June 2014, respectively. Both patients were right-handed men and
      presented with progressive plaques and nodules, which they had for several years,
      involving the right upper extremity. Skin biopsy from the granuloma was taken and
      cultured on Sabouraud medium, and molecular identification based on the
      calmodulin region was performed. Antifungal susceptibility testing was also
      performed with the microdilution method. RESULTS: Biopsy of the lesions showed
      the presence of infectious granuloma. The fungal cultures were identified as
      Sporothrix globosa by conventional methods, and confirmed by molecular
      identification. A subsequent course of oral antifungal therapy with low dosage of
      itraconazole was well tolerated and resolved the infection. CONCLUSIONS:
      Identification of fungal species and antifungal susceptibility testing are
      mandatory for epidemiological and therapeutic reasons. Early diagnosis of
      sporotrichosis is essential to prevent those sequelae when the disease progresses
      and provides highly effective methods for treating this emerging disease.
      Avoiding the exposure to plant material potentially contaminated with fungal
      spores should be recommended, especially in immunocompromised patients.

PMID- 25982355
TI  - Hepatothorax: a rare presentation to the trauma surgeon.

PMID- 25982356
TI  - Pigment organisation in the membrane-intrinsic major light-harvesting complex of
      Amphidinium carterae: Structural characterisation of the peridinins and
      chlorophylls a and c2 by resonance Raman spectroscopy and from sequence analysis.
AB  - The structures and environments of the protein-bound peridinins (Pers) and
      chlorophylls (Chls) a/c2 in the membrane-intrinsic major light-harvesting complex
      of the dinoflagellate Amphidinium carterae (LHCAmph) are characterised using
      resonance Raman (RR) spectroscopy with 11 excitation wavelengths, at 77K. The
      excitation-dependent variation in the CC stretching mode (nu1) suggests the
      presence of three Pers with conjugation lengths over 8 double bonds (dBs), and
      one diadinoxanthin, between 413.7 and 528.7nm. Two Perred species are revealed on
      excitation at 550 and 560nm. These Perred species exhibit anomalously low nu1
      values, together with notable resonant enhancement of lactone ring-breathing and 
      deformation modes. To discern protein-specific effects, the RR spectra are
      compared to that of Per in polar (acetonitrile), polarisable (toluene) and polar
      protic (ethanol) solvents. Resonantly enhanced lactone, ring-breathing (942cm(
      1)) and ring-deformation (~650cm(-1)), modes are identified both in solution, and
      in the protein, and discussed in the context of the mixing of the S1 and S2
      states, and formation of the intramolecular charge-transfer (ICT) state. In the
      Chl-absorbing region, two sets of Chl c2's, and (at least) six Chl a's can be
      differentiated. With a pigment ratio of 5-6 (Chl a):2 (Chl c2):5-6 (Per):1 Ddx
      determined from the fit to the RT absorption and 77K RR spectra, sequence
      comparison of LHCAmp to LHCII, and the diatom LHC, fucoxanthin-chlorophyll-a/c
      protein (FCP), a template for the conserved pigment binding sites is proposed, to
      fill the paucity of structural information in the absence of a crystal structure
      for LHCAmph. 

PMID- 25982357
TI  - Solution structure of the NDH-1 complex subunit CupS from Thermosynechococcus
      elongatus.
AB  - The cyanobacterial multi-subunit membrane protein complex NDH-1 is both
      structurally and functionally related to Complex I of eubacteria and
      mitochondria. In addition to functions in respiration and cyclic electron
      transfer around photosystem I (PSI), the cyanobacterial NDH-1 complex is involved
      in a unique mechanism for inorganic carbon concentration. Although the crystal
      structures of the similar respiratory Complex I from Thermus thermophilus and
      Escherichia coli are known, atomic structural information is not available for
      the cyanobacterial NDH-1 complex yet. In particular, the structures of those
      subunits that are not homologous to Complex I will help to understand their
      distinct functions. The 15.7kDa protein CupS is a small soluble subunit of the
      complex variant NDH-1MS, which is thought to play a role in CO2 conversion. Here,
      we present the NMR structure of CupS from Thermosynechococcus elongatus, which is
      the very first structure of a specific cyanobacterial NDH-1 complex subunit. CupS
      shares a structural similarity with members of the Fasciclin protein superfamily.
      The structural comparison to Fasciclin type proteins based on known NMR
      structures and protein sequences of human TGFBIp, MPB70 from Mycobacterium bovis,
      and Fdp from Rhodobacter sphaeroides, together with a virtual docking model of
      CupS and NdhF3, provide first insight into the specific binding of CupS to the
      NDH-1MS complex at atomic resolution. 

PMID- 25982358
TI  - Effects of low molecular weight hyaluronan combined with carprofen on canine
      osteoarthritis articular chondrocytes and cartilage explants in vitro.
AB  - Intra-articular injection with non-steroidal anti-inflammatory drugs (NSAIDs) is
      used to treat inflammatory joint disease, but the side effects of NSAIDs include
      chondrotoxicity. Hyaluronan has shown positive effects on chondrocytes by
      reducing apoptosis and increasing proteoglycan synthesis. The purposes of this
      study were to evaluate the effects of low molecular weight hyaluronan (low MW
      HA), carprofen 25 mg/ml, carprofen 12.5 mg/ml, and a combination of HA and
      carprofen on canine osteoarthritis (OA) articular chondrocytes and a cartilage
      explant model in terms of cell viability, extracellular matrix remaining, and
      gene expression after exposure. In chondrocyte culture, MTT assay was used to
      evaluate the chondrotoxicity of IC50 and IC80 of carprofen with HA. In cartilage
      explant culture, two kinds of extracellular matrix (uronic acid and collagen)
      remaining in cartilage were used to evaluate cartilage damage for 14 d after
      treatment. Expression of COL2A1, AGG, and MMP3 was used to evaluate the synthesis
      and degradation of the matrix for 7 d after treatment. In chondrocyte culture,
      low MW HA could preserve OA chondrocyte viability but could not reduce the
      chondrotoxicity level of carprofen (P < 0.05). In explant culture, low MW HA
      combined with 12.5 mg/ml carprofen caused less destruction of uronic acid and
      collagen structure when compared with the control (P < 0.05). Low MW HA caused
      high expression levels of COL2A1 and AGG in OA cartilage (P < 0.05); HA combined
      with carprofen resulted in higher COL2A1 and AGG expression levels than carprofen
      alone.

PMID- 25982359
TI  - Coexisting congenital dysfibrinogenemia with a novel mutation in fibrinogen gamma
      chain (gamma322 Phe->Ile, Fibrinogen Beijing) and haemophilia B in a family.
AB  - INTRODUCTION: Both congenital dysfibrinogenemia and haemophilia B (HB) are rare
      coagulopathies caused by mutations within the fibrinogen and F9 genes
      respectively. AIM: To investigate the pathogenesis of combined dysfibrinogenemia
      with HB in a family. METHODS: Coagulation assays, factor IX (FIX) activity (one
      stage method), fibrinogen activity (Clauss method), antigen (immunoturbidimetry),
      fibrinogen polymerization and fibrinolysis velocity were measured. The sequences
      of fibrinogen genes and F9 were amplified by PCR and analysed by sequencing.
      RESULTS: The proband, a 16-year-old boy with HB (FIX 2 IU dL(-1) ), also had
      persistently low Clauss fibrinogen level (0.64-0.65 g L(-1) ) with normal antigen
      level (2.23 g L(-1) ). The mother had a FIX 45 IU dL(-1) and similarly discrepant
      low Clauss fibrinogen (0.79 g L(-1) ) to antigen levels (2.23 g L(-1) ). Thrombin
      time for both were either slightly prolonged or at boundary value. Genetic
      analysis of the proband and the mother identified similar mutations in the FGG
      gene (heterozygous c.1042T>A resulting in p.Phe348Ile or gammaPhe322Ile in the
      mature protein) and in the F9 gene (c.1243del p.His415Metfs*11 and c.1245T>A
      p.His415Gln). The father had no fibrinogen or F9 gene mutations. Plasma
      fibrinogen polymerization was delayed, but fibrinolysis velocity was normal in
      the proband and his mother. CONCLUSION: To our knowledge, this is the first
      report of a family with combined novel dysfibrinogen (Fibrinogen Beijing) and HB
      with bleeding manifestations.

PMID- 25982360
TI  - Prenatal diagnosis of Pierre Robin Sequence: accuracy and ability to predict
      phenotype and functional severity.
AB  - OBJECTIVE: To assess the outcome of fetuses who had sonographic features
      suggestive of Pierre Robin Sequence (PRS). METHOD: All prenatal ultrasounds that
      mentioned 'posterior cleft palate', or 'micro or retrognathia' or 'PRS' over 13
      and 20 years, respectively, at two obstetrical centers were reviewed. Medical
      records for children with isolated PRS monitored over 20 years at a PRS referral
      center for prenatal anomalies and the severity of neonatal feeding and
      respiratory functional disorders were utilized for comparison. RESULTS: From a
      prenatal ultrasound database of 166 000 cases, 157 had one or more of the
      sonographic signs suggestive of PRS and had follow-up available. Of them, 33
      (21%) had confirmed PRS, 9 (6%) were normal and 115 (73%) had chromosomal
      aberrations, associated malformations or neurological anomalies. Visualization of
      a posterior cleft palate in addition to retro-micrognathia had a positive
      predictive value of 100% for PRS. The distribution of functional severity grades
      was similar in cases suspected prenatally as in 238 cases of PRS followed in the
      referral center in Necker Hospital. CONCLUSION: Only a minority of cases of fetal
      retrognathia have complete PRS; the majority have other severe conditions.
      Prenatal prediction of functional severity of isolated PRS is not possible.

PMID- 25982361
TI  - Attitudes on fertility issues in breast cancer patients: an Italian survey.
AB  - BACKGROUND: Fertility issues should be discussed with young women before the
      start of any anticancer treatment. The study is aimed to investigate the attitude
      on fertility among Italian oncologists and breast surgeons dealing with BCa, and
      to report the consensus achieved on specific statements. METHODS: One hundred and
      sixty-two panelists anonymously expressed an opinion through a web-based platform
      on 19 statements based on the Delphi method. RESULTS: Ninety-one percent of
      oncologists considered important to discuss with patients about fertility issues
      and 83% believed estrogens could stimulate the growth of hidden cancer cells in
      ER(+) tumors. Difficulties in accessing fertility preservation procedures were
      mainly due to patients' reluctance, but also to lack of coordination with the
      assisted reproduction specialists. No full consensus was reached on the
      prognostic role of pregnancy after BCa. Fifty-four percent of oncologists
      declared that pregnancy does not affect oncologic prognosis. Treatment with GnRHa
      during chemotherapy was considered the only mean for preserving ovarian function.
      CONCLUSIONS: Fertility preservation in BCa patients is a well-accepted practice
      among Italian oncologists. A poor knowledge of this specific issue emerged from
      the survey, even if a certain degree of agreement was observed on most fertility
      related issues.

PMID- 25982362
TI  - Scheduling GnRH antagonist cycles by a short course of oral estradiol
      administration during early follicular phase: a comparative study with non
      scheduled cycles.
AB  - This hypothesis generating study investigated whether GnRH antagonist cycles can
      be scheduled by a short course of oral estradiol administration during the
      follicular phase without impairing treatment outcome. Thirty-five women who
      underwent follicular phase estrogen scheduling (ES) of GnRH antagonist cycles
      were retrospectively matched for age and number of prior failed cycles with 35
      women who underwent unscheduled GnRH antagonist cycles. ES group was given 6
      mg/day estradiol orally from cycle day 2 until (including) one day before the
      scheduled start of stimulation. Gonadotropins were started on cycle days 2-3 in
      the control group. Flexible GnRH antagonist protocol was employed in both groups.
      ES group received estradiol for a median of 5 days. Total gonadotropin
      consumption was similar but one more GnRH antagonist injection was required in
      the ES group. Endometrial thickness on the day of hCG injection was increased in
      the ES group (12 versus 10 mm, p < 0.01). Number of oocytes, metaphase II oocytes
      and transferred embryos were similar. Embryo implantation rates were 44.8% versus
      34.4% (p = 0.3), and clinical pregnancy rates were 48.6% versus 37.1%, (p = 0.33)
      in the ES and control groups, respectively. All women in the ES group had oocyte
      retrieval and embryo transfer within the desired period. 

PMID- 25982364
TI  - Effects of non-amputative wide local excision on the local control and prognosis
      of in situ and invasive subungual melanoma.
AB  - Subungual melanomas (SUM) are rare, and amputation is often required. Non
      amputative wide local excision (WLE) of the nail unit with the periosteum of the
      distal phalanx, followed by skin graft, has been accepted for in situ or SUM of
      0.5 mm or less thickness. However, previous reports have included a limited
      number of cases, and not all more than 0.5-mm thick SUM exhibit invasion or
      attachment to the distal phalanx. The aim of the present study was to investigate
      the local recurrence and prognosis for in situ, minimally invasive and invasive
      SUM that were treated using WLE. We retrospectively reviewed 50 patients with in
      situ (n = 48) or minimally invasive SUM (n = 2) (in situ or minimally invasive
      group) and 12 patients with more than 0.5-mm thick invasive SUM (invasive group)
      who were treated using WLE. All patients survived the follow-up period (24-207
      months), although four patients with in situ SUM experienced local recurrence at
      the lateral margin and re-excision was required. In the invasive group, no
      patients experienced local recurrence, although one patient (8.3%) developed
      nodal metastasis at 86 months and regional lymph node dissection was required.
      WLE may provide acceptable local control for in situ and intermediate thickness
      SUM, without compromising the vital prognosis. However, a larger randomized
      prospective study with long-term follow up is required to evaluate adequately the
      risks associated with a non-amputative WLE for in situ and invasive SUM. 

PMID- 25982365
TI  - Caution is recommended prior to sildenafil use in vascular anomalies.
AB  - Since publication of a single case report of lymphatic malformation improvement
      during sildenafil therapy for pulmonary hypertension, sildenafil use has
      propagated across multiple vascular anomalies diagnoses. Vascular anomalies are
      rare conditions, often with poor long-term outcomes from available therapies,
      making these patients vulnerable to novel therapy use. We have retrospectively
      reviewed 14 children with vascular anomalies treated with sildenafil. None of
      these patients reported improvement of disease while on treatment and some
      reported side effects including infections and bleeding. Pending more convincing
      prospective data, we recommend caution prior to sildenafil use for vascular
      anomalies.

PMID- 25982363
TI  - Biology-Driven Gene-Gene Interaction Analysis of Age-Related Cataract in the
      eMERGE Network.
AB  - Bioinformatics approaches to examine gene-gene models provide a means to discover
      interactions between multiple genes that underlie complex disease. Extensive
      computational demands and adjusting for multiple testing make uncovering genetic
      interactions a challenge. Here, we address these issues using our knowledge
      driven filtering method, Biofilter, to identify putative single nucleotide
      polymorphism (SNP) interaction models for cataract susceptibility, thereby
      reducing the number of models for analysis. Models were evaluated in 3,377
      European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a
      study site of the Electronic Medical Records and Genomics (eMERGE) Network, using
      logistic regression. All statistically significant models from the Marshfield
      Clinic were then evaluated in an independent dataset of 4,311 individuals (742
      controls, 3,569 cases), using independent samples from additional study sites in
      the eMERGE Network: Mayo Clinic, Group Health/University of Washington,
      Vanderbilt University Medical Center, and Geisinger Health System. Eighty-three
      SNP-SNP models replicated in the independent dataset at likelihood ratio test P <
      0.05. Among the most significant replicating models was rs12597188 (intron of
      CDH1)-rs11564445 (intron of CTNNB1). These genes are known to be involved in
      processes that include: cell-to-cell adhesion signaling, cell-cell junction
      organization, and cell-cell communication. Further Biofilter analysis of all
      replicating models revealed a number of common functions among the genes
      harboring the 83 replicating SNP-SNP models, which included signal transduction
      and PI3K-Akt signaling pathway. These findings demonstrate the utility of
      Biofilter as a biology-driven method, applicable for any genome-wide association
      study dataset. 

PMID- 25982366
TI  - Admission glucose and risk of early death in non-diabetic patients with ST
      segment elevation myocardial infarction: a meta-analysis.
AB  - BACKGROUND: Impaired admission glucose (AG) is considered to significantly
      increase risk on both early and late death of the patients with ST-segment
      elevation myocardial infarction (STEMI), especially for non-diabetic patients;
      however, some reports contradict the relationship. We therefore conducted a meta
      analysis to clarify this issue. MATERIAL/METHODS: PubMed, EMBASE, Web of Science,
      and Cochrane Library databases were systematically searched to identify all
      related prospective cohort studies. The relative risks (RR) with their 95%
      confidence interval (CI) were pooled quantitatively. RESULTS: The pooled RR of
      early outcome events indicated patients with glucose concentrations >=6.1-11.1
      mmol/L had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. The pooled RR
      of late outcome events indicated that the patients with glucose concentrations
      >=7.8-11.1 mmol/L had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based
      on in-hospital or 30-day survivors. CONCLUSIONS: High AG may be a helpful
      prognostic marker of significantly increased risk on early death in non-diabetic
      patients with STEMI, and has an explicit but prognostic adverse impact on long
      term mortality but not early mortality in these patients.

PMID- 25982367
TI  - Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal
      Neurons Are Controlled by a Medial Septal Glutamatergic Circuit.
AB  - Before the onset of locomotion, the hippocampus undergoes a transition into an
      activity-state specialized for the processing of spatially related input. This
      brain-state transition is associated with increased firing rates of CA1 pyramidal
      neurons and the occurrence of theta oscillations, which both correlate with
      locomotion velocity. However, the neural circuit by which locomotor activity is
      linked to hippocampal oscillations and neuronal firing rates is unresolved. Here
      we reveal a septo-hippocampal circuit mediated by glutamatergic (VGluT2(+))
      neurons that is activated before locomotion onset and that controls the
      initiation and velocity of locomotion as well as the entrainment of theta
      oscillations. Moreover, via septo-hippocampal projections onto alveus/oriens
      interneurons, this circuit regulates feedforward inhibition of Schaffer
      collateral and perforant path input to CA1 pyramidal neurons in a locomotion
      dependent manner. With higher locomotion speed, the increased activity of medial
      septal VGluT2 neurons is translated into increased axo-somatic depolarization and
      higher firing rates of CA1 pyramidal neurons. VIDEO ABSTRACT.

PMID- 25982368
TI  - The loss in expectation of life after colon cancer: a population-based study.
AB  - BACKGROUND: To demonstrate how assessment of life expectancy and loss in
      expectation of life can be used to address a wide range of research questions of
      public health interest pertaining to the prognosis of cancer patients. METHODS:
      We identified 135,092 cases of colon adenocarcinoma diagnosed during 1961-2011
      from the population-based Swedish Cancer Register. Flexible parametric survival
      models for relative survival were used to estimate the life expectancy and the
      loss in expectation of life. RESULTS: The loss in expectation of life for males
      aged 55 at diagnosis was 13.5 years (95 % CI 13.2-13.8) in 1965 and 12.8 (12.4
      13.3) in 2005. For males aged 85 the corresponding figures were 3.21 (3.15-3.28)
      and 2.10 (2.04-2.17). The pattern was similar for females, but slightly greater
      loss in expectation of life. The loss in expectation of life is reduced given
      survival up to a certain time point post diagnosis. Among patients diagnosed in
      2011, 945 life years could potentially be saved if the colon cancer survival
      among males could be brought to the same level as for females. CONCLUSION:
      Assessment of loss in expectation of life facilitates the understanding of the
      impact of cancer, both on individual and population level. Clear improvements in
      survival among colon cancer patients have led to a gain in life expectancy,
      partly due to a general increase in survival from all causes.

PMID- 25982369
TI  - Diffuse idiopathic skeletal hyperostosis (DISH) of the elbow: a controlled
      radiological study.
AB  - BACKGROUND: Extraspinal manifestations of diffuse idiopathic skeletal
      hyperostosis (DISH) have been described previously. We aimed to assess the
      prevalence of elbow hyperostotic spurs, to search for sites discriminating for
      elbow DISH and to analyze the effect of physical activities, handedness and sex.
      METHODS: Out of 284 patients hospitalized for extraskeletal disorders, 85
      patients (33 with and 52 without thoracospinal DISH) agreed to bilateral elbow X
      rays in two projections. Clinical information was collected by a standardized
      questionnaire and X-rays were graded blindly. RESULTS: A total of 400
      hyperostotic spurs (210 unilateral, 95 bilateral) were present at 11 predefined
      sites. The most frequent sites affected were the olecranon (20.8%), lateral
      epicondyle (17.8%) and medial epicondyle (15.5%). In carriers of thoracospinal
      DISH significantly more hyperostotic spurs were present at the lateral and medial
      epicondyle compared to non-DISH carriers (OR 4.01 [95% CI 1.35-12.34] and 2.88
      [1.03-8.24], respectively). The olecranon, lateral and medial epicondyle
      contributed significantly to the classification of elbow DISH (OR 22.2 [4.1
      144.7], 9.6 [1.9-61.2] and 10.1 [2.2-52.1], respectively). The prevalence of
      elbow hyperostotic spurs was higher in 45 patients with a history of heavy
      physical activities (24.4% versus 18.0%, OR 1.48 [1.17-1.86]), at the right elbow
      (24.2% versus 18.6%, OR 1.39 [1.11-1.75]) and in 62 males (22.8% versus 17.6%, OR
      1.38 [1.06-1.81]). CONCLUSIONS: Hyperostotic spurs at the olecranon, lateral and
      medial epicondyle had the highest prevalence and disclosed the most pronounced
      discrimination for elbow DISH. Mechanical factors such as physical activities and
      handedness, and sex influenced the formation of these spurs.

PMID- 25982370
TI  - 6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells
      and enhance the efficacy of T cell immunotherapy in tumor-bearing mice.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of
      immature myeloid cells that suppress effector T cell responses and can reduce the
      efficacy of cancer immunotherapies. We previously showed that ultra-small polymer
      nanoparticles efficiently drain to the lymphatics after intradermal injection and
      target antigen-presenting cells, including Ly6c(hi) Ly6g(-) monocytic MDSCs (Mo
      MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra
      small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used
      in the treatment of myelogenous leukemia, with the aim of killing Mo-MDSCs in
      tumor-bearing mice and thus enhancing T cell-mediated anti-tumor responses. We
      found that 2 days post-injection in tumor-bearing mice (B16-F10 melanoma or E.G7
      OVA thymoma), MC-TG depleted Mo-MDSCs in the spleen, Ly6c(lo) Ly6g(+)
      granulocytic MDSCs (G-MDSCs) in the draining LNs, and Gr1(int) Mo-MDSCs in the
      tumor. In both tumor models, MC-TG decreased the numbers of circulating Mo- and G
      MDSCs, as well as of Ly6c(hi) macrophages, for up to 7 days following a single
      administration. MDSC depletion was dose dependent and more effective with MC-TG
      than with equal doses of free TG. Finally, we tested whether this MDSC-depleting
      strategy might enhance cancer immunotherapies in the B16-F10 melanoma model. We
      found that MC-TG significantly improved the efficacy of adoptively transferred,
      OVA-specific CD8(+) T cells in melanoma cells expressing OVA. These findings
      highlight the capacity of MC-TG in depleting MDSCs in the tumor microenvironment
      and show promise in promoting anti-tumor immunity when used in combination with T
      cell immunotherapies.

PMID- 25982371
TI  - Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and
      immunogenicity in a phase I clinical study.
AB  - We report on the safety and immunogenicity of idiotypic DNA vaccination in a
      phase I, non-randomised, open-label study in patients with multiple myeloma. The
      study used DNA fusion gene vaccines encoding patient-specific single chain
      variable fragment, or idiotype (Id), linked to fragment C (FrC) of tetanus toxin.
      Patients in complete or partial response following high-dose chemotherapy and
      autologous stem cell transplant were vaccinated intramuscularly with 1 mg DNA on
      six occasions, beginning at least 6 months post-transplant; follow-up was to week
      52. Fourteen patients were enrolled on study and completed vaccinations.
      Idiotypic DNA vaccines were well tolerated with vaccine-related adverse events
      limited to low-grade constitutional symptoms. FrC- and Id-specific T-cell
      responses were detected by ex vivo ELISPOT in 9/14 and 3/14 patients,
      respectively. A boost of pre-existing anti-FrC antibody (Ab) was detected by
      ELISA in 8/14 patients, whilst anti-Id Ab was generated in 1/13 patients.
      Overall, four patients (29 %) made an immune response to FrC and Id, with six
      patients (43 %) responding to FrC alone. Over the 52-week study period, serum
      paraprotein was undetectable, decreased or remained stable for ten patients (71
      %), whilst ongoing CR/PR was maintained for 11 patients (79 %). The median time
      to progression was 38.0 months for 13/14 patients. Overall survival was 64 %
      after a median follow-up of 85.6 months.

PMID- 25982372
TI  - Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients
      with hepatitis C virus-related hepatocellular carcinoma: a phase 1 dose
      escalation clinical trial.
AB  - BACKGROUND: We previously reported overexpression of heat-shock protein (HSP) 70
      in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) using proteomic
      profiling and immunohistochemical staining (IHS). This suggested that HSP70 could
      be a molecular target for treatment of HCC. METHODS: Twelve patients with HCV
      related HCC were enrolled in a phase 1 clinical trial. Dendritic cells (DCs)
      transfected with HSP70 mRNA (HSP70-DCs) induced by electroporation were injected
      intradermally. Patients were treated three times every 3 weeks. The number of
      HSP70-DCs injected was 1 * 10(7) as the lowest dose, then 2 * 10(7) as the medium
      dose, and then 3 * 10(7) as the highest dose. Immunological analyses were
      performed. FINDINGS: No adverse effects of grade III/IV, except one grade III
      liver abscess at the 3 * 10(7) dose, were observed. Thus, we added three more
      patients to confirm whether 3 * 10(7) is an appropriate dose. Eventually, we
      chose 3 * 10(7) as the recommended dose of DCs. Complete response (CR) without
      any recurrence occurred in two patients, stable disease in five, and progression
      of disease in five. The two patients with CR have had no recurrence for 44 and 33
      months, respectively. IHS in one patient who underwent partial hepatectomy showed
      infiltration of CD8+ T cells and granzyme B in tumors, indicating that the
      dominant immune effector cells were cytotoxic T lymphocytes with tumor-killing
      activity. INTERPRETATION: This study demonstrated that HSP70-DCs therapy is both
      safe and feasible in patients with HCV-related HCC. Further clinical trials
      should be considered.

PMID- 25982373
TI  - Organ-specific monocyte activation in necrotizing pancreatitis in mice.
AB  - BACKGROUND: Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory
      response syndrome. We investigated the underlying changes of monocytes using
      different activation markers. MATERIALS AND METHODS: A retrograde injection of 2
      mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice
      induced NAP, whereas sham-operated animals (SOP) were treated with saline. After
      6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin
      6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid
      were examined. Isolation of mononuclear cells from the blood, spleen, and liver
      and the subsequent determination of macrophages (F4/80) and their activation
      marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell
      sorting (FACS analyses). RESULTS: After pancreatitis induction, pancreatic
      enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P < 0.001) and histologic
      pancreatic damage (SOP 0.80 +/- 1.92, NAP 19.6 +/- 0.64, P < 0.001) developed
      instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h
      after onset (6 h albumin SOP 132.0 +/- 12.0 MUg/mL, NAP 267.2 +/- 49.6 MUg/mL; P
      < 0.05; MPO SOP 0.23 +/- 0.20 ng/mL, NAP 11.29 +/- 3.12 ng/mL, P < 0.01). Blood
      levels of interleukin 6 increased after 12-24 h (12 h SOP 584 +/- 300 pg/mL; NAP
      2169 +/- 942 pg/mL, P < 0.05), whereas monocytes increased fourfold within 48 h
      (P < 0.05). Furthermore, pancreatitis increased the percentage of activated
      monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b
      51,654%/82,146%). Similar observations were made for monocytes from the liver and
      spleen. CONCLUSIONS: Although inflammatory mediators increased during 24 h after
      pancreatitis induction, monocyte activation lasted for at least 48 h. The latter
      is not limited to blood but also detected in isolated liver and spleen monocytes.

PMID- 25982374
TI  - Hyperbaric oxygen effects on neuronal apoptosis associations in a traumatic brain
      injury rat model.
AB  - BACKGROUND: The neuroprotective mechanisms of hyperbaric oxygen (HBO) therapy on
      traumatic brain injury (TBI) remain unclear, especially neuronal apoptosis
      associations such as the expression of tumor necrosis factor alpha (TNF-alpha),
      transforming growth-interacting factor (TGIF), and TGF-beta1 after TBI. The aim
      of this study was to investigate the neuroprotective effects of HBO therapy in a
      rat model of TBI. MATERIALS AND METHODS: The experimental rats were randomly
      divided into three groups as follows: TBI + normobaric air (21% O2 at one
      absolute atmosphere), TBI + HBO, and sham-operated normobaric air. The TBI + HBO
      rats received 100% O2 at 2.0 absolute atmosphere for 1 h immediately after TBI.
      Local and systemic TNF-alpha expression, neuropathology, levels of the neuronal
      apoptosis-associated proteins TGIF and TGF-beta1, and functional outcome were
      evaluated 72 h after the onset of TBI. RESULTS: Compared to the TBI control
      groups, the running speed of rats on the TreadScan after TBI was significantly
      attenuated by HBO therapy. The TBI-induced local and systemic TNF-alpha
      expression, neuronal damage score, and neuronal apoptosis were also significantly
      reduced by HBO therapy. Moreover, HBO treatment attenuated the expression of TGIF
      but increased TGF-beta1 expression in neurons. CONCLUSIONS: We concluded that
      treatment of TBI with HBO during the acute phase of injury can decrease local and
      systemic proinflammatory cytokine TNF-alpha production, resulting in
      neuroprotective effects. We also suggest that decreased levels of TGIF and
      increased levels of TGF-beta in the injured cortex leading to decreased neuronal
      apoptosis is one mechanism by which functional recovery may occur.

PMID- 25982375
TI  - Inpatient outcomes after elective versus nonelective ventral hernia repair.
AB  - BACKGROUND: Patients who present emergently with hernia-related concerns may
      experience increased morbidity with repair when compared with those repaired
      electively. We sought to characterize the outcomes of patients who undergo
      elective and nonelective ventral hernia (VH) repair using a large population
      based data set. MATERIALS AND METHODS: The Nationwide Inpatient Sample was
      queried for primary International Classification of Diseases, Ninth Revision
      codes associated with VH repair (years 2008-2011). Outcomes were inhospital
      mortality and the occurrence of a preidentified complication. Multivariable
      analysis was performed to determine the risk factors for complications and
      mortality after both elective and nonelective VH repair. RESULTS: We identified
      74,151 VH repairs performed during the study interval. Of these procedures, 67.3%
      were elective and 21.6% were performed laparoscopically. Nonelective repair was
      associated with a significantly higher rate of morbidity (22.5% versus 18.8%, P <
      0.01) and mortality (1.8% versus 0.52, P < 0.01) than elective repair. Elective
      repairs were more likely to occur in younger patients, Caucasians, and were more
      likely to be performed laparoscopically. Logistic modeling revealed that female
      gender, Caucasian race, elective case status, and laparoscopic approach were
      independently associated with a lower probability of complications and mortality.
      Minority status and Medicaid payer status were associated with increased
      probability of nonelective admission. CONCLUSIONS: Patients undergoing elective
      VH repair in the United States tend to be younger, Caucasian, and more likely to
      have a laparoscopic repair. Nonelective VH is associated with a substantial
      increase in morbidity and mortality. We recommend that patients consider elective
      repair of VHs because of the increased morbidity and mortality associated with
      nonelective repair.

PMID- 25982376
TI  - The novel tumor angiogenic factor, adrenomedullin-2, predicts survival in
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Tumor angiogenesis has been demonstrated to have an important role in
      the development, progression, and metastasis of pancreas cancer. Adrenomedullin-2
      (ADM2) is a calcitonin gene-related peptide that has recently been shown to be a
      novel tumor angiogenesis factor, acting via mitogen-activated protein
      kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinase/Akt, and
      vascular endothelial growth factor/vascular endothelial growth factor-2 signaling
      pathways. Through the use of tissue microarray (TMA) technology, we hypothesize
      that ADM2 is an important tumor angiogenesis factor in pancreatic cancer.
      METHODS: Multiple TMAs were created using tissue from pancreatic cancer patients
      resected between January 1996 and December 2006. Core tissue samples of formalin
      fixed, paraffin-embedded blocks of pancreatic cancer tissue were collected
      through an institutional review board-approved protocol and linked to available
      clinicopathologic data. Two TMAs consisting of 112 and 60 patients with
      pancreatic adenocarcinoma were studied for ADM2 protein expression using a
      quantitative, automated immunofluorescent microscopy system, a technology that
      removes potential observer bias in TMA analysis. The results were analyzed using
      independent Student t-test, chi-square, log-rank regression, and Kaplan-Meier
      methods. RESULTS: One hundred sixteen patients were identified for complete
      analysis, and 56 patients had complete survival data. Median follow-up for
      survivors was 14.5 mo. Total cellular levels of ADM2 were found to be a predictor
      of survival in pancreatic cancer. Low ADM2 levels were associated with a higher 5
      y survival compared with high ADM2 levels (18% versus 6%, P = 0.05). Median
      survival was also worse in high ADM2 expressers (18.7 versus 8.6 mo). In
      accordance with prior-published pancreatic cancer data, a worse histologic grade
      (P = 0.001), tumor (T) stage (P = 0.009), and overall disease stage (P = 0.004),
      all portended a worse survival. CONCLUSIONS: For the first time, we have
      demonstrated that high levels of ADM2 expression predict a poorer survival in
      patients with pancreatic adenocarcinoma. This suggests a possible role of ADM2 in
      pancreas cancer and as a novel biomarker that predicts poorer survival.
      Additional study of ADM2 in pancreatic cancer will help reveal its true
      angiogenic role in pancreas cancer and its potential role as a novel therapeutic
      target.

PMID- 25982378
TI  - Association of haematological parameters with bone mineral density in elderly
      diabetic women.
AB  - OBJECTIVES: In this study, we aimed to evaluate whether an association exists
      between complete blood count (CBC) parameters and bone mineral density (BMD) in
      elderly females with type 2 diabetes mellitus (T2DM) and to estimate the
      differences in BMD in T2DM. METHODS: The medical records of female patients who
      had been referred for BMD analysis to a tertiary hospital in Ankara, Turkey were
      reviewed. RESULTS: A total of 275 women (66 with T2DM, 209 without T2DM; mean age
      72.1 +/- 5.4 years) were included in study. White blood cell (WBC) counts, lumbar
      spine BMD (LSBMD) and femoral neck BMD (FNBMD) were found to be significantly
      higher in T2DM. There was an inverse association between haematocrit (Hct) and
      LSBMD in diabetic group (r =  - 0.330; P = 0.008). CONCLUSION: Diabetic patients
      had higher BMD levels. Regardless of the mechanisms, Hct could be a readily
      available potential candidate to identify diabetic patients with osteoporosis.

PMID- 25982379
TI  - New perspectives on lenticulostriate vasculopathy in neonates.

PMID- 25982380
TI  - Intramyocardial Delivery of Notch Ligand-Containing Hydrogels Improves Cardiac
      Function and Angiogenesis Following Infarction.
AB  - Myocardial infarction (MI) is the leading cause of death worldwide. Notch1
      signaling plays a critical role in cardiac development, in survival, cardiogenic
      lineage commitment, differentiation of cardiac stem/progenitor cells, and in
      regenerative responses following myocardial injury. The objective of this study
      was the evaluation of the therapeutic effect of delivering the Notch ligand
      containing hydrogels in a rat model of MI. Self-assembling peptide (SAP)
      hydrogels were functionalized with a peptide mimic of the Notch1 ligand Jagged1
      (RJ). In rats subjected to experimental MI, delivery of RJ-containing hydrogel to
      the infarcted heart resulted in improvement in cardiac function back to sham
      operated levels. A significant decrease in fibrosis and an increase in the
      endothelial vessel area and Ki67 expression were also observed in rats treated
      with the RJ hydrogels compared to untreated rats or rats treated with unmodified
      or scrambled peptide hydrogels. This study demonstrates the functional benefit of
      Notch1-activating peptide delivered in SAP hydrogels for cardiac repair.

PMID- 25982382
TI  - Cystic Fibrosis Frequently Asked Questions: Question 4: What is the appropriate
      duration of therapy for respiratory exacerbations in Cystic Fibrosis patients
      infected with Pseudomonas aeruginosa?

PMID- 25982383
TI  - Quantitative time-course proteome analysis of Mesorhizobium loti during nodule
      maturation.
AB  - Rhizobia are nitrogen-fixing bacteria that establish a symbiotic relationship
      with leguminous plants. To understand the mechanism by which rhizobia alter their
      metabolism to establish successful nitrogen-fixing symbiotic relationship with
      hosts, Lotus japonicus were inoculated with Mesorhizobium loti. Bacteroids were
      isolated from nodules harvested at 2weeks (the early stage of nodule
      development), and at 3 and 4weeks (the intermediate stage of nodule development)
      post-inoculation. Using a quantitative time-course proteome analysis, we
      quantified the variations in the production of 537 proteins in M. loti bacteroids
      during the course of nodule maturation. The results revealed significant changes
      in the carbon and amino acid metabolisms by M. loti upon differentiating into
      bacteroids. Furthermore, our findings suggested that M. loti enters a nitrogen
      deficient condition during the early stages of nodule development, and then a
      nitrogen-rich condition during the intermediate stages of nodule development. In
      addition, our data indicated that M. loti assimilated ammonia during the
      intermediate stages of nodule development. Our results provide new insights into
      the course of physiological transitions undergone by M. loti during nodule
      maturation. 

PMID- 25982381
TI  - DNA methylation changes in the placenta are associated with fetal manganese
      exposure.
AB  - Adequate micronutrient intake, including manganese (Mn), is important for fetal
      development. Both Mn deficiencies and excess exposures are associated with later
      life disease, and Mn accumulates in the placenta. Placental functional
      alterations may alter fetal programming and lifelong health, and we hypothesized
      that prenatal exposures to Mn may alter placental function through epigenetic
      mechanisms. Using Illumina's HumanMethylation450 BeadArray, DNA methylation of
      >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn
      associations assessed genome-wide via omnibus test (p=0.045). 713 loci were
      associated with Mn exposure (p<0.0001). Five significantly differentially
      methylated (p<1.3*10(-7)) loci reside in neurodevelopmental, fetal growth and
      cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was
      associated with birth weight; for every 10% increase in methylation, lower birth
      weights were observed, with an average decrease of 293.44g. Our observations
      suggest a link between prenatal micronutrient levels, placental epigenetic status
      and birth weight, although these preliminary results require validation. 

PMID- 25982384
TI  - Quantitative comparison of CrkL-SH3 binding proteins from embryonic murine brain
      and liver: Implications for developmental signaling and the quantification of
      protein species variants in bottom-up proteomics.
AB  - A major aim of proteomics is to comprehensively identify and quantify all protein
      species variants from a given biological source. However, in spite of its
      tremendous utility, bottom-up proteomic strategies can do little to provide true
      quantification of distinct whole protein species variants given its reliance on
      proteolysis. This is particularly true when molecular size information is lost as
      in gel-free proteomics. Crk and CrkL comprise a family of adaptor proteins that
      couple upstream phosphotyrosine signals to downstream effectors by virtue of
      their SH2 and SH3 domains respectively. Here we compare the identification and
      quantification of CrkL-SH3 binding partners between embryonic murine brain and
      liver. We also uncover and quantify tissue-specific variants in CrkL-SH3 binding
      proteins. 

PMID- 25982385
TI  - LC-MS-based serum metabolomic analysis reveals dysregulation of
      phosphatidylcholines in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers
      with poor prognosis. Here, we carried out liquid chromatography-quadrupole time
      of-flight mass spectrometry (LC-Q-TOF-MS)-based untargeted metabolomic analysis
      of ESCC serum samples. Statistical analysis resulted in the identification of 652
      significantly dysregulated molecular features in serum from ESCC patients as
      compared to the healthy subjects. Phosphatidylcholines were identified as a major
      class of dysregulated metabolites in this study suggesting potential perturbation
      of phosphocholine metabolism in ESCC. By using a targeted MS/MS approach both in
      positive and negative mode, we were able to characterize and confirm the
      structure of seven metabolites. Our study describes a quantitative LC-MS approach
      for characterizing dysregulated lipid metabolism in ESCC. BIOLOGICAL
      SIGNIFICANCE: Altered metabolism is a hallmark of cancer. We carried out (LC-MS)
      based untargeted metabolomic profiling of serum from esophageal squamous cell
      carcinoma (ESCC) patients to characterize dysregulated metabolites.
      Phosphatidylcholine metabolism was found to be significantly altered in ESCC. Our
      study illustrates the use of mass spectrometry-based metabolomic analysis to
      characterize molecular alterations associated with ESCC. This article is part of
      a Special Issue entitled: Proteomics in India.

PMID- 25982386
TI  - Multicenter experiment for quality control of peptide-centric LC-MS/MS analysis -
      A longitudinal performance assessment with nLC coupled to orbitrap MS analyzers.
AB  - Proteomic technologies based on mass spectrometry (MS) have greatly evolved in
      the past years, and nowadays it is possible to routinely identify thousands of
      peptides from complex biological samples in a single LC-MS/MS experiment. Despite
      the advancements in proteomic technologies, the scientific community still faces
      important challenges in terms of depth and reproducibility of proteomics
      analyses. Here, we present a multicenter study designed to evaluate long-term
      performance of LC-MS/MS platforms within the Spanish Proteomics Facilities
      Network (ProteoRed-ISCIII). The study was performed under well-established
      standard operating procedures, and demonstrated that it is possible to attain
      qualitative and quantitative reproducibility over time. Our study highlights the
      importance of deploying quality assessment metrics routinely in individual
      laboratories and in multi-laboratory studies. The mass spectrometry data have
      been deposited to the ProteomeXchange Consortium with the data set identifier
      PXD000205.This article is part of a Special Issue entitled: HUPO 2014. 

PMID- 25982387
TI  - Proteomic analysis of Plasmodium falciparum induced alterations in humans from
      different endemic regions of India to decipher malaria pathogenesis and identify
      surrogate markers of severity.
AB  - India significantly contributes to the global malaria burden and has the largest
      population in the world at risk of malaria. This study aims to analyze
      alterations in the human serum proteome as a consequence of non-severe and severe
      infections by the malaria parasite Plasmodium falciparum to identify markers
      related to disease severity and to obtain mechanistic insights about disease
      pathogenesis and host immune responses. In discovery phase of the study, a
      comprehensive quantitative proteomic analysis was performed using gel-based (2D
      DIGE) and gel-free (iTRAQ) techniques on two independent mass spectrometry
      platforms (ESI-Q-TOF and Q-Exactive mass spectrometry), and selected targets were
      validated by ELISA. Proteins showing altered serum abundance in falciparum
      malaria patients revealed the modulation of different physiological pathways
      including chemokine and cytokine signaling, IL-12 signaling and production in
      macrophages, complement cascades, blood coagulation, and protein ubiquitination
      pathways. Some muscle related and cytoskeletal proteins such as titin and
      galectin-3-binding protein were found to be up-regulated in severe malaria
      patients. Hemoglobin levels and platelet counts were also found to be drastically
      lower in severe malaria patients. Identified proteins including serum amyloid A,
      C-reactive protein, apolipoprotein E and haptoglobin, which exhibited sequential
      alterations in their serum abundance in different severity levels of malaria,
      could serve as potential predictive markers for disease severity. To the best of
      our information, we report here the first comprehensive analysis describing the
      serum proteomic alterations observed in severe P. falciparum infected patients
      from different malaria endemic regions of India. This article is part of a
      Special Issue entitled: Proteomics in India.

PMID- 25982388
TI  - The human RBPome: from genes and proteins to human disease.
AB  - RNA binding proteins (RBPs) play a central role in mediating post transcriptional
      regulation of genes. However less is understood about them and their regulatory
      mechanisms. In this study, we construct a catalogue of 1344 experimentally
      confirmed RBPs. The domain architecture of RBPs enabled us to classify them into
      three groups - Classical (29%), Non-classical (19%) and unclassified (52%). A
      higher percentage of proteins with unclassified domains reveals the presence of
      various uncharacterised motifs that can potentially bind RNA. RBPs were found to
      be highly disordered compared to Non-RBPs (p<2.2e-16, Fisher's exact test),
      suggestive of a dynamic regulatory role of RBPs in cellular signalling and
      homeostasis. Evolutionary analysis in 62 different species showed that RBPs are
      highly conserved compared to Non-RBPs (p<2.2e-16, Wilcox-test), reflecting the
      conservation of various biological processes like mRNA splicing and ribosome
      biogenesis. The expression patterns of RBPs from human proteome map revealed that
      ~40% of them are ubiquitously expressed and ~60% are tissue-specific. RBPs were
      also seen to be highly associated with several neurological disorders, cancer and
      inflammatory diseases. Anatomical contexts like B cells, T-cells, foetal liver
      and foetal brain were found to be strongly enriched for RBPs, implying a
      prominent role of RBPs in immune responses and different developmental stages.
      The catalogue and meta-analysis presented here should form a foundation for
      furthering our understanding of RBPs and the cellular networks they control, in
      years to come. This article is part of a Special Issue entitled: Proteomics in
      India.

PMID- 25982389
TI  - Maternal micronutrient deficiency leads to alteration in the kidney proteome in
      rat pups.
AB  - Maternal nutritional deficiency significantly perturbs the offspring's physiology
      predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate
      are two such micronutrients, whose deficiency leads to elevated homocysteine
      levels. We earlier generated B12 and/or folate deficient rat models and using
      high-throughput proteomic approach, showed that maternal vitamin B12 deficiency
      modulates carbohydrate and lipid metabolism in the liver of pups through
      regulation of PPAR signaling pathway. In this study, using similar approach, we
      identified 26 differentially expressed proteins in the kidney of pups born to
      mothers fed with vitamin B12 deficient diet while only four proteins were
      identified in the folate deficient group. Importantly, proteins like
      calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in
      the functioning of the kidney were upregulated in B12 deficient group. Our
      results hint towards a larger effect of vitamin B12 deficiency compared to that
      of folate presumably due to greater elevation of homocysteine in vitamin B12
      deficient group. In view of widespread vitamin B12 and folate deficiency and its
      association with several diseases like anemia, cardiovascular and renal diseases,
      our results may have large implications for kidney diseases in populations
      deficient in vitamin B12 especially in vegetarians and the elderly people.This
      article is part of a Special Issue entitled: Proteomics in India.

PMID- 25982390
TI  - The processing of food stimuli in abnormal eating: a systematic review of
      electrophysiology.
AB  - To update the knowledge about attentional processing of food stimuli, a
      systematic review of electrophysiological studies was conducted using PubMed,
      PsychInfo and Web of Knowledge (2000-2014). Twenty-one studies were included into
      a qualitative synthesis. Presentation of food and control pictures was used to
      analyze event-related potentials related to sensory processing and motivated
      attention. Results show consistent attentional bias towards food pictures
      compared with neutral pictures for patient and control groups. Group comparisons
      between individuals with abnormal-eating and healthy-eating participants were
      more inconsistent. Results suggest that temporal differences in the millisecond
      range are essential for the understanding of visual food processing. In obesity,
      early attention engagement to food is followed by relatice disengagement. Loss of
      control eating, as well as external and emotional eating, are associated with a
      sustained maintenance of attention towards high-caloric food. There is a lack of
      studies in anorexia nervosa, bulimia nervosa and binge eating disorder.

PMID- 25982391
TI  - The effect of Hop (Humulus lupulus L.) on early menopausal symptoms and hot
      flashes: A randomized placebo-controlled trial.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy of Hop on early menopausal
      symptoms and hot flashes. METHODS: In this randomized controlled trial, 120 women
      were randomly allocated into two groups, receiving the Hop or placebo tablets for
      12 weeks. Early menopausal symptoms were assessed using Greene scale and hot
      flashes were recorded in a diary before, and 4, 8 and 12 weeks after
      intervention. RESULTS: The mean Greene score was significantly lower in the Hop
      group than the placebo group at the end of weeks 4 (adjusted difference: -10.0,
      95% confidence interval: -11.1--8.9), 8 (-18.6, -20.1--17.1) and 12 (-23.4, -25.1
      -21.6). The number of hot flashes was significantly lower in the Hop group than
      the control group during the weeks 4 (-8.4, -9.8--7.1), 8 (-17.1, -14.9--19.3)
      and 12 (-23.8, -21.1--26.4). CONCLUSIONS: Hop effectively reduced the early
      menopausal symptoms. CLINICAL TRIAL REGISTRATION: This study was approved (code
      91209) by the Ethic Committee of Tabriz university of Medical Sciences and
      registered at the Iranian registry of clinical trials, with IRCT 2013010110324N7
      on April 2013.

PMID- 25982392
TI  - Women's use of complementary and alternative medicine in pregnancy: Narratives of
      transformation.
AB  - BACKGROUND: Pregnancy and childbirth constitute a time of transition in women's
      lives. Many women turn to complementary and alternative medicines (CAM) during
      pregnancy. However, little is known about women's experiences of CAM in relation
      to their pregnancy and childbirth journey. METHODS: a narrative study aimed to
      gain insight into the experiences of women who use CAM in pregnancy and to
      explore the contribution CAM made to their pregnancy and childbirth journey.
      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. RESULTS: This paper
      presents some findings from this research which reveals a narrative genre that
      can be defined as transformational. CAM has a positive transformational effect on
      women's experience of pregnancy and childbirth. CONCLUSION: Women's narratives
      illustrate the positive impact of CAM on the subjective experiences of pregnancy
      and childbirth.

PMID- 25982393
TI  - Targeting of multiple oncogenic signaling pathways by Hsp90 inhibitor alone or in
      combination with berberine for treatment of colorectal cancer.
AB  - There is a wide range of drugs and combinations under investigation and/or
      approved over the last decade to treat colorectal cancer (CRC), but the 5-year
      survival rate remains poor at stages II-IV. Therefore, new, more-efficient drugs
      still need to be developed that will hopefully be included in first-line therapy
      or overcome resistance when it appears, as part of second- or third-line
      treatments in the near future. In this study, we revealed that heat shock protein
      90 (Hsp90) inhibitors have high therapeutic potential in CRC according to
      combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and
      chemical genomic database of Connectivity Map (CMap). We found that second
      generation Hsp90 inhibitor, NVP-AUY922, significantly downregulated the
      activities of a broad spectrum of kinases involved in regulating cell growth
      arrest and death of NVP-AUY922-sensitive CRC cells. To overcome NVP-AUY922
      induced upregulation of survivin expression which causes drug insensitivity, we
      found that combining berberine (BBR), a herbal medicine with potency in
      inhibiting survivin expression, with NVP-AUY922 resulted in synergistic
      antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells.
      Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells
      with the combination of NVP-AUY922 and BBR caused cell growth arrest through
      inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated
      suppression of Pin1-beta-catenin-cyclin D1 signaling pathway. Finally, we found
      that the expression level of Hsp90 in tumor tissues of CRC was positively
      correlated with CDK4 and Pin1 expression levels. Taken together, these results
      indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple
      oncogenic signaling pathways of CRC. 

PMID- 25982394
TI  - Particle design of drug delivery system.

PMID- 25982397
TI  - A first survey on the biochemical composition of egg yolk and lysozyme-like
      activity of egg envelopment in the cuttlefish Sepia officinalis from the Northern
      Adriatic Sea (Italy).
AB  - The cuttlefish Sepia officinalis is an important fishery resource in the Northern
      Adriatic Sea (Italy). During reproduction, fertilised eggs are released by adult
      females in coastal waters and embryo development can take over two months. During
      this period, embryos rely on nutrients and other substances, such as immune
      factors, provided by the female in egg yolk. In cephalopods in general, and
      specifically in the common cuttlefish, little information is available on yolk
      biochemical composition and substances included in egg envelopment. In the
      present study, the main biochemical components of egg yolk and the presence of
      antimicrobial substances in egg envelopment of S. officinalis were determined for
      the first time. Statistically significant differences in total egg weight and egg
      yolk weight were observed among batches from different females. Egg and yolk
      weights were positively correlated, with yolk representing the 13% (+/-5%) of the
      total egg weight. Total proteins were the main biochemical component (46%) of egg
      yolk, followed by total carbohydrates plus glycogen (39%) and lipids (15%).
      Statistically significant differences among batches were recorded in egg yolk
      total protein amounts, lipids, carbohydrates and glycogen, but no correlations
      were found between egg yolk weight and the biochemical components. The Petri dish
      and the quantitative spectrophotometric assays revealed the presence of lysozyme
      like activity in egg gelatinous envelopment.

PMID- 25982395
TI  - Structural, functional, and evolutionary aspects of galectins in aquatic
      mollusks: From a sweet tooth to the Trojan horse.
AB  - Galectins constitute a conserved and widely distributed lectin family
      characterized by their binding affinity for beta-galactosides and a unique
      binding site sequence motif in the carbohydrate recognition domain (CRD). In
      spite of their structural conservation, galectins display a remarkable functional
      diversity, by participating in developmental processes, cell adhesion and
      motility, regulation of immune homeostasis, and recognition of glycans on the
      surface of viruses, bacteria and protozoan parasites. In contrast with mammals,
      and other vertebrate and invertebrate taxa, the identification and
      characterization of bona fide galectins in aquatic mollusks has been relatively
      recent. Most of the studies have focused on the identification and domain
      organization of galectin-like transcripts or proteins in diverse tissues and cell
      types, including hemocytes, and their expression upon environmental or infectious
      challenge. Lectins from the eastern oyster Crassostrea virginica, however, have
      been characterized in their molecular, structural and functional aspects and some
      notable features have become apparent in the galectin repertoire of aquatic
      mollusks. These including less diversified galectin repertoires and different
      domain organizations relative to those observed in vertebrates, carbohydrate
      specificity for blood group oligosaccharides, and up regulation of galectin
      expression by infectious challenge, a feature that supports their proposed
      role(s) in innate immune responses. Although galectins from some aquatic mollusks
      have been shown to recognize microbial pathogens and parasites and promote their
      phagocytosis, they can also selectively bind to phytoplankton components,
      suggesting that they also participate in uptake and intracellular digestion of
      microalgae. In addition, the experimental evidence suggests that the protozoan
      parasite Perkinsus marinus has co-evolved with the oyster host to be selectively
      recognized by the oyster hemocyte galectins over algal food or bacterial
      pathogens, thereby subverting the oyster's innate immune/feeding recognition
      mechanisms to gain entry into the host cells. 

PMID- 25982396
TI  - Identification and expression analysis on bactericidal permeability-increasing
      protein/lipopolysaccharide-binding protein of blunt snout bream, Megalobrama
      amblycephala.
AB  - Bactericidal permeability-increasing protein (BPI) and lipopolysaccharide-binding
      protein (LBP) belong to the lipid transfer protein/lipopolysaccharide-binding
      protein family and play a critical role in the innate immune response to Gram
      negative bacteria. In the present study, a novel BPI/LBP from blunt snout bream,
      Megalobrama amblycephala (maBPI/LBP) was isolated by RACE techniques. The open
      reading frame (ORF) of maBPI/LBP gene encoded a polypeptide of 474 amino acids
      with a putative 18-aa hydrophobic signal peptide. Structurally, the maBPI/LBP
      showed highly similar to those of BPI/LBPs from invertebrate and teleost, LBPs
      and BPIs from mammal, which contained an N-terminal BPI/LBP/CETP domain BPI1 with
      a LPS-binding domain, a C-terminal BPI/LBP/CETP domain BPI2, and proline-rich
      domain. The homologous identities of deduced amino acid sequences displayed that
      the maBPI/LBP possessed significant similarity (96.61% and 90.07%) with those of
      grass carp and common carp, respectively. The recombinant protein of maBPI/LBP
      showed effectively kill Gram-negative bacteria. The maBPI/LBP gene was expressed
      in a wide range of normal tested tissues, with the highest expression levels in
      the kidney. The experiments revealed that the mRNA expression of maBPI/LBP in
      spleen considerably up-regulated from 2 h to 8 h post LPS stimulation, and peaked
      rapidly at 2 h (7.40-fold, P < 0.05), which confirmed that maBPI/LBP was the
      absolute sensitive to LPS stimulation. Furthermore, the level of maBPI/LBP mRNA
      expression reached the maximum for a second time at 24 h after LPS stimulation.
      These results suggested that maBPI/LBP was a constitutive and inducible acute
      phase protein contributing to the host immune defense against pathogenic
      bacterial infection in M. amblycephala. This study will further our understanding
      of the function of BPI/LBP and the molecular mechanism of innate immunity in
      teleost.

PMID- 25982398
TI  - Molecular characterization and immune response expression of the QM gene from the
      scallop Chlamys farreri.
AB  - The scallop Chlamys farreri is an important aquaculture species in northern
      China. However, the sustainable development of the scallop industry is currently
      threatened by several pathogens that cause mass mortality of this mollusk.
      Therefore, a complete understanding of the immune response mechanisms involved in
      host-virus interactions is necessary. This study reports a novel QM gene from C.
      farreri. This gene was first identified as a putative tumor suppressor gene from
      human and then confirmed to participate in several functions, including immune
      response. The QM gene from C. farreri (CfQM) was identified by suppression
      subtractive hybridization, and its full-length (763 bp) cDNA was obtained through
      rapid amplification of cDNA ends. The cDNA of CfQM contained a short 5'-UTR of 22
      bp and a 3'-UTR of 84 bp. Its ORF comprised 657 nucleotides that encode 218 amino
      acids with a molecular weight of approximately 28.3 kDa and an isoelectric point
      of 10.06. The deduced amino acid sequence of CfQM contained a series of conserved
      functional motifs that belong to the QM family. Phylogenetic analysis revealed
      that CfQM was closely related to other mollusk QM proteins, and altogether they
      form a mollusk QM protein subfamily that displays evolutionary conservation from
      yeast to human. The tissue-specific expression and transcriptional regulation of
      CfQM were investigated by quantitative real-time PCR in response to bacterial
      (Vibrio anguillarum) and viral (acute viral necrobiotic virus) challenges. The
      transcript level of CfQM was high in all of the examined tissues in a
      constitutive manner. The highest and lowest expression levels of CfQM were
      measured in the hepatopancreas and hemocyte, respectively. Upon bacterial and
      viral challenges, the relative mRNA expression of CfQM sharply increased at 6 h
      post-infection (hpi) and then normalized at 48 hpi. These findings suggest that
      CfQM can respond to and protect against pathogen challenge. To the best of our
      knowledge, this study is the first report of the QM gene from scallop. The
      results presented herein provided new insights into the molecular basis of host
      pathogen interactions in C. farreri.

PMID- 25982400
TI  - Development and function of pearl-sacs grown from regenerated mantle graft tissue
      in the black-lip pearl oyster, Pinctada margaritifera (Linnaeus, 1758).
AB  - Current pearl grafting techniques were developed in the early 1900s and have
      changed little since. They involve the sacrifice of donor pearl oysters to
      provide graft tissue (saibo) that is implanted into host oysters. This study
      assessed the feasibility of using regenerated graft tissue for pearl production
      in the 'black-lip' pearl oyster, Pinctada margaritifera. Twelve days after
      grafting with regenerated graft tissue, there was complete encapsulation of the
      nucleus by the fully developed pearl-sac and the first layer of organic matrix
      had been secreted. Sixteen days after grafting, the pearl-sac was completely
      integrated with host tissue. The epithelial cells in the pearl-sac continued to
      secrete the organic matrix layer but there were no signs of nacre deposition at
      this stage. However, after three months of culture, nuclei in oysters grafted
      with regenerated mantle tissue were completely covered with nacre. The average
      nacre thickness on pearls produced from regenerated (0.547 +/- 0.01 mm, n = 8)
      and normal (0.532 +/- 0.01 mm, n = 8) mantle tissue did not differ significantly
      (p > 0.05). Nacre secretion rates, over the 80 day period subsequent to pearl-sac
      formation were 6.84 +/- 0.1 MUm day(-1) and 6.66 +/- 0.1 MUm day(-1) for oysters
      grafted with regenerated and normal mantle tissue, respectively. These means were
      not significantly different (p = 0.258). Our results clearly show that
      regenerated mantle tissue can function successfully as saibo for pearl production
      in P. margaritifera. This finding could provide significant benefits to pearl
      farmers and a basis for further development of current pearl grafting practices.

PMID- 25982399
TI  - Interaction study of a novel Macrobrachium rosenbergii effector caspase with B2
      and capsid proteins of M. rosenbergii nodavirus reveals their roles in apoptosis.
AB  - Apoptosis is an essential immune response to protect invertebrates from virus
      infected cells. In shrimp, virus infection has been reported to induce apoptosis.
      Macrobrachium rosenbergii (Mr) was considered to be a disease-resistant host when
      compared to penaeid shrimps. Caspase-3 was classified as an executioner caspase
      which played a key role in virus-induced apoptosis. In this study, an effector
      caspase gene of M. rosenbergii (Mrcasp) was cloned and characterized. The open
      reading frame (ORF) of Mrcasp was 957 nucleotide encoding 318 amino acid with a
      deduced molecular mass of 35.87 kDa. RT-PCR analysis showed the presence of
      Mrcasp in all examined tissues. The phylogenetic tree indicated that Mrcasp was
      closely related with caspase 3 of shrimp. The functions of the Mrcasp, B2 and
      capsid proteins of M. rosenbergii nodavirus (MrNV) were assayed in Sf-9 cells.
      The results showed that Mrcasp induce apoptotic morphology cells; however, capsid
      protein of MrNV could inhibit apoptotic cells whereas B2 could neither induce nor
      inhibit apoptotic cells by DAPI staining. The protein interaction between Mrcasp
      and viral MrNV structure revealed that Mrcasp did not bind to B2 or capsid
      protein whereas B2 and capsid proteins could bind directly to each other. This
      study reported a novel sequence of a full-length Mrcasp and its functional
      studies indicated that Mrcasp could induce apoptotic cells. Our data is the first
      report demonstrating the direct protein-protein interaction between capsid
      protein and B2 protein of MrNV.

PMID- 25982401
TI  - Transcriptomic analysis of Mandarin fish brain cells infected with infectious
      spleen and kidney necrosis virus with an emphasis on retinoic acid-inducible gene
      1-like receptors and apoptosis pathways.
AB  - Infectious spleen and kidney necrosis virus (ISKNV) has caused significant
      economic losses in the cultured Mandarin fish (Siniperca chuatsi) industry. The
      molecular mechanisms that underlie the pathogenesis of the viral infection remain
      poorly understood. In this study, deep RNA sequencing technique was used to
      analyze the transcriptomic profiles of Mandarin fish brain cells (CPB) at
      progressive time points after ISKNV infection. A total of 96,206,040 clean data
      from 98,235,240 sequence reads were obtained. These raw data were assembled into
      66,787 unigenes. Among these unigenes, 33,225 and 29,210 had significant hit the
      Nr and SwissProt databases where they matched 27,537and 19,638 unique protein
      accessions, respectively. In the samples harvested at 24 or 72 h post of the
      infection, a total of 10,834 or 7584 genes were differentially expressed in
      infected CPB cells compared to non-infected cells, including 5445 or 3766 up
      regulated genes and 5389 or 3818 down-regulated genes, respectively. In addition,
      12 differentially expressed genes (DEGs) were validated by quantitative PCR.
      These DEGs were involved in many pathways of viral pathogenesis. Further analysis
      of the major DEGs genes involved in the RLRs and apoptosis pathways revealed some
      interesting findings. In the RLRs pathway, ISKNV infection inhibited the
      activation of NF-kappaB via over expression of the IKKB-alpha and IKKB-beta and
      lessened expression of interleukin-1 receptor-associated kinase 4 (IRAK4). In the
      apoptosis pathway, ISKNV infection could induce apoptosis mainly via tumor
      necrosis factor (TNF) mediated extrinsic pathway. The cellular apoptosis induced
      by ISKNV infection was confirmed using annexinV-FITC/PI and DAPI staining
      methods.

PMID- 25982402
TI  - Understanding the cephalopod immune system based on functional and molecular
      evidence.
AB  - Cephalopods have the most advanced circulatory and nervous system among the
      mollusks. Recently, they have been included in the European directive which state
      that suffering and pain should be minimized in cephalopods used in
      experimentation. The knowledge about cephalopod welfare is still limited and
      several gaps are yet to be filled, especially in reference to pathogens,
      pathologies and immune response of these mollusks. In light of the requirements
      of the normative, in addition to the ecologic and economic importance of
      cephalopods, in this review we update the work published to date concerning
      cephalopod immune system. Significant advances have been reached in relation to
      the characterization of haemocytes and defensive mechanisms comprising cellular
      and humoral factors mainly, but not limited, in species of high economic value
      like Sepia officinalis and Octopus vulgaris. Moreover, the improvement of
      molecular approaches has helped to discover several immune-related
      genes/proteins. These immune genes/proteins include antimicrobial peptides,
      phenoloxidases, antioxidant enzymes, serine protease inhibitor,
      lipopolysaccharide-induced TNF-alpha factor, Toll-like receptors, lectins, even
      clusters of differentiation among others. Most of them have been found in
      haemocytes but also in gills and digestive gland, and the characterization as
      well as their precise role in the immune response of cephalopods is still pending
      to be elucidated. The assessment of immune parameters in cephalopods exposed to
      contaminants is just starting, but the negative impact of some pollutants on the
      immune response of the common octopus has been reported. This review summarizes
      the current status of our knowledge about the cephalopod immune system that seems
      to be far from simply. On the contrary, the advances gained to date point out a
      complex innate immunity in cephalopods. 

PMID- 25982403
TI  - Molecular profiles and pathogen-induced transcriptional responses of prawn B cell
      lymphoma-2 related ovarian killer protein (BOK).
AB  - In this study, we have reported a molecular characterization of the first B cell
      lymphoma-2 (BCL-2) related ovarian killer protein (BOK) from freshwater prawn
      Macrobrachium rosenbergii (Mr). BOK is a novel pro-apoptotic protein of the BCL-2
      family that entails in mediating apoptosis to remove cancer cells. A cDNA
      sequence of MrBOK was identified from the prawn cDNA library and its full length
      was obtained by internal sequencing. The coding region of MrBOK yields a
      polypeptide of 291 amino acids. The analysis revealed that MrBOK contains a
      transmembrane helix at V(261)-L(283) and a putative BCL-2 family domain at V(144)
      W(245). MrBOK also possessed four putative BCL-2 homology domains including BH1,
      BH2, BH3 and weak BH4. The BH3 contains 21 binding sites and among them five
      residues are highly conserved with the aligned BOK proteins. The homology
      analysis showed that MrBOK shared maximum similarity with the Caligus
      rogercresseyi BOK A. The topology of the phylogenetic tree was classified into
      nine sister groups which includes BOK, BAK, BAX, BAD, BCL-2, BCL-XL, NR13 and MCL
      members. The BOK protein group further sub-grouped into vertebrate and
      invertebrate BOK, wherein MrBOK located within insect monophyletic clad of
      invertebrate BOK. The secondary structural analysis showed that MrBOK contains 11
      alpha-helices (52.2%) which are connected over random coils (47.7%). The 3D
      structure of MrBOK showed three central helices (alpha6, alpha7 and alpha8) which
      formed the core of the protein and are flanked on one side by alpha1, alpha2 and
      alpha3, and on the other side by alpha4, alpha5 and alpha11. MrBOK mRNA is
      expressed most abundantly (P < 0.05) in ovary compared to other tissues taken for
      analysis. Hence ovary was selected to study the possible roles of MrBOK mRNA
      regulation upon bacterial (Aeromonas hydrophila and Vibrio harveyi) and viral
      [white spot syndrome virus (WSSV) and M. rosenbergii nodovirus] infection. During
      bacterial and viral infection, the highest MrBOK mRNA transcription was varied at
      different time points. In bacterial infected ovary tissue, the highest mRNA
      expression was at 24 h post-infection, whereas in viral infection, the expression
      was highest at 48 h post-infection. Thus we can conclude that MrBOK functions as
      an apoptotic protein in intracellular programmed cell-death pathway to counteract
      the anti-apoptotic proteins released by bacterial and viral pathogens at the time
      of infection. This is the first study that emphasizes the importance of BOK
      during bacterial and viral infection in crustacean.

PMID- 25982404
TI  - ORF75 of megalocytivirus RBIV-C1: A global transcription regulator and an
      effective vaccine candidate.
AB  - Megalocytivirus, a DNA virus belonging to the Iridoviridae family, is a severe
      pathogen to a wide range of marine and freshwater fish. In this study, using
      turbot (Scophthalmus maximus) as a host model, we examined the immunoprotective
      property of one megalocytivirus gene, ORF75, in the form of DNA vaccine (named
      pORF75). Immunofluorescence microscopy and RT-PCR analysis showed that P444, the
      protein encoded by ORF75, was naturally produced in the tissues of turbot during
      megalocytivirus infection, and that the vaccine gene in pORF75 was expressed in
      fish cells transfected with pORF75 and in the tissues of turbot immunized with
      pORF75. Following vaccination of turbot with pORF75, a high level of survival
      (73%) was observed against a lethal megalocytivirus challenge. Consistently,
      viral replication in the vaccinated fish was significantly inhibited. Immune
      response analysis showed that pORF75-vaccinated fish (i) exhibited upregulated
      expression of the genes involved in innate and adaptive immunity, (ii) possessed
      specific memory immune cells that showed significant response to secondary
      antigen stimulation, and (iii) produced specific serum antibodies which, when co
      introduced into turbot with megalocytivirus, blocked viral replication.
      Furthermore, whole-genome transcriptome analysis revealed that ORF75 knockdown
      altered the transcription of 43 viral genes. Taken together, these results
      indicate that ORF75 encoded a highly protective immunogen that is also a global
      transcription regulator of megalocytivirus.

PMID- 25982405
TI  - Developing tools for the study of molluscan immunity: The sequencing of the
      genome of the eastern oyster, Crassostrea virginica.
AB  - The eastern oyster, Crassostrea virginica, provides important ecological and
      economical services, making it the target of restoration projects and supporting
      a significant fishery/aquaculture industry with landings valued at more than $100
      million in 2012 in the United States of America. Due to the impact of infectious
      diseases on wild, restored, and cultured populations, the eastern oyster has been
      the focus of studies on host-pathogen interactions and immunity, as well as the
      target of selective breeding efforts for disease resistant oyster lines. Despite
      these efforts, relatively little is known about the genetic basis of resistance
      to diseases or environmental stress, not only in eastern oyster, but also in
      other molluscan species of commercial interest worldwide. In order to develop
      tools and resources to assist in the elucidation of the genomic basis of traits
      of commercial, biological, and ecological interest in oysters, a team of genome
      and bioinformatics experts, in collaboration with the oyster research community,
      is sequencing, assembling, and annotating the first reference genome for the
      eastern oyster and producing an exhaustive transcriptome from a variety of oyster
      developmental stages and tissues in response to a diverse set of environmentally
      relevant stimuli. These transcriptomes and reference genome for the eastern
      oyster, added to the already available genome and transcriptomes for the Pacific
      oyster (Crassostrea gigas) and other bivalve species, will be an essential
      resource for the discovery of candidate genes and markers associated with traits
      of commercial, biological, and ecologic importance in bivalve molluscs, including
      those related to host-pathogen interactions and immunity.

PMID- 25982406
TI  - Identification of a myeloperoxidase-like ortholog from rock bream (Oplegnathus
      fasciatus), deciphering its transcriptional responses to induced pathogen stress.
AB  - Myeloperoxidases (MPOs) are heme-linked oxidative stress-generating enzymes found
      abundantly in azurophilic granules of polymorphonuclear neutrophils. Mature MPOs
      act as potent antimicrobial agents by producing hypohalous acids using hydrogen
      peroxide and halide ions as substrates. These acids can readily oxidize reactive
      groups of biomolecules on invading microbes. In this study, we identified and
      characterized a homolog of MPO from rock bream (Oplegnathus fasciatus),
      designated as RbMPO. We analyzed the RbMPO gene for its basal expression level in
      physiologically important tissues and for transcriptional changes under different
      pathogenic stress conditions. The complete coding sequence of RbMPO consisted of
      2652 nucleotides encoding an 884 amino acid sequence with a predicted molecular
      mass of 99.7 kDa. Our in silico analysis confirmed the typical MPO domain
      arrangement in RbMPO, including the propeptide, large chain and heavy chain,
      along with the heme peroxidase signature. Intriguingly, a C1q domain was also
      identified in the C-terminal region of the derived amino acid sequence. Most of
      the known functionally important residues of MPOs are found to be well conserved
      in RbMPO, showing a close evolutionary relationship with other teleostan MPOs,
      particularly with that of mandarin fish. RbMPO exhibited a ubiquitous basal
      expression in physiologically relevant tissues, with particularly high expression
      levels in blood cells. Basal transcript levels of RbMPO in gill and spleen
      tissues were found to change upon different pathogen or pathogen-derived mitogen
      stimulation, with detectable inductive responses. Together, these data suggest
      the potential involvement of RbMPO in the innate immune response in rock bream.

PMID- 25982407
TI  - Effects of bisphenol A and 17beta-estradiol on vascular endothelial growth factor
      A and its receptor expression in the non-cancer and cancer ovarian cell lines.
AB  - Tumours secrete several pro-angiogenic factors, among which vascular endothelial
      growth factor (VEGF) and its receptor (VEGF-R) are the most extensively studied
      but not in ovarian cancer cells. The study was designed to investigate the effect
      of bisphenol A (BPA) (environmental oestrogen) and of 17beta-estradiol (E2)
      (endogenous estrogen) on the gene (real-time PCR) and protein (Western blotting)
      expression of VEGF-R2 and VEGF-A in human non-cancer (HOSEpiC) and ovarian cancer
      cell lines (SKOV-3 and OVCAR-3). In addition, VEGF-A levels were measured in
      culture supernatants using a colorimetric assay. Cells were exposed to BPA (1, 40
      and 100 nM) or 17beta-estradiol (0.1, 10 and 40 nM) for 3 to 48 h. Since
      differential expression levels of basal oestrogen receptor (ERalpha and ERbeta)
      between non-cancer and cancer cell lines may affect the response to oestrogens,
      receptor expression was measured both at the gene and protein levels. Basal
      ERbeta expression was similar in all cell lines, and ERalpha expression was
      significantly higher in the SKOV-3 cell line. Basal VEGF-R2 expression was higher
      in cancer than non-cancer cell lines, and in contrast, VEGF-A expression was
      significantly lower in both SKOV-3 and OVCAR-3 cancer cell lines. Exposure of non
      cancer cells to BPA and E2 was associated with a significant increase in VEGF-R2
      expression but had no effect on VEGF-A expression or secretion. In contrast,
      exposure of cancer cells to BPA, but not E2, increased VEGF-R2 and VEGF-A
      expression and secretion. In conclusion, (1) BPA and E2 regulated VEGF-R2 and
      VEGF-A expression differently in non-cancer and cancer cells, and (2) BPA has a
      direct stimulatory effect on VEGF-R2 and VEGF-A expression in both, while E2
      appears to be uninvolved in the regulation of VEGF-R2 and VEGF-A expression in
      cancer cells. Graphical Abstract A schematic representation showing BPA and E2
      action on VEGF-R2 and VEGF-A expression in non-cancer (HOSEpiC) and cancer cells
      (SKOV-3, OVCAR-3).

PMID- 25982408
TI  - Investigation of citric acid-glycerol based pH-sensitive biopolymeric hydrogels
      for dye removal applications: A green approach.
AB  - Hydrogels are three dimensional polymeric structure with segments of hydrophilic
      groups. The special structure of hydrogels facilitates the diffusion of solutes
      into the interior network and possess numerous ionic and non-ionic functional
      groups, which can absorb or trap ionic dyes from waste water. The present
      investigation was devoted to the synthesis of a series of citric acid and
      glycerol based pH sensitive biopolymeric hydrogels using a solventless green
      approach via condensation polymerization in the presence of acidic medium. The
      formations of hydrogels were confirmed using various spectral investigations
      viz., FT-IR, (1)H and (13)C NMR. The thermal properties of various hydrogels have
      been studied using TGA, DTA and DSC analysis. The rationalized relationship was
      noticed with increasing of pH from 4.0 to 10.0. The surface morphologies of
      hydrogels were analyzed using SEM technique which was well supported from the
      results of swelling studies. Methylene blue has been selected as a cationic dye
      for its removal from various environmental sources using pH-sensitive
      biopolymeric hydrogels. The results of dye removal revealed that glycerol based
      biopolymeric hydrogels have shown an excellent dye removal capacity. Hence, the
      synthesized pH sensitive biopolymeric hydrogels have an adaptability with pH
      tuned properties might have greater potential opening in various environmental
      applications viz., metal ion removal, agrochemical release, purification of
      water, dye removal etc. 

PMID- 25982409
TI  - Fabrication of zirconia composite membrane by in-situ hydrothermal technique and
      its application in separation of methyl orange.
AB  - The main objective of the work was preparation of zirconia membrane on a low cost
      ceramic support through an in-situ hydrothermal crystallization technique for the
      separation of methyl orange dye. To formulate the zirconia film on the ceramic
      support, hydrothermal reaction mixture was prepared using zirconium oxychloride
      as a zirconia source and ammonia as a precursor. The synthesized zirconia powder
      was characterized by X-ray diffractometer (XRD), N2 adsorption/desorption
      isotherms, Thermogravimetric analysis (TGA), Fourier transform infrared analysis
      (FTIR), Energy-dispersive X-ray (EDX) analysis and particle size distribution
      (PSD) to identify the phases and crystallinity, specific surface area, pore
      volume and pore size distribution, thermal behavior, chemical composition and
      size of the particles. The porosity, morphological structure and pure water
      permeability of the prepared zirconia membrane, as well as ceramic support were
      investigated using the Archimedes' method, Field emission scanning electron
      microscopy (FESEM) and permeability. The specific surface area, pore volume, pore
      size distribution of the zirconia powder was found to be 126.58m(2)/g, 3.54nm and
      0.3-10um, respectively. The porosity, average pore size and pure water
      permeability of the zirconia membrane was estimated to be 42%, 0.66um and
      1.44*10(-6)m(3)/m(2)skPa, respectively. Lastly, the potential of the membrane was
      investigated with separation of methyl orange by means of flux and rejection as a
      function of operating pressure and feed concentration. The rejection was found to
      decrease with increasing the operating pressure and increases with increasing
      feed concentrations. Moreover, it showed a high ability to reject methyl orange
      from aqueous solution with a rejection of 61% and a high permeation flux of
      2.28*10(-5)m(3)/m(2)s at operating pressure of 68kPa. 

PMID- 25982411
TI  - Experience- and age-mediated oviposition behaviour in the yellow fever mosquito
      Stegomyia aegypti (=Aedes aegypti).
AB  - In repeated behaviours such as those of feeding and reproduction, past
      experiences can inform future behaviour. By altering their behaviour in response
      to environmental stimuli, insects in highly variable landscapes can tailor their
      behaviour to their particular environment. In particular, female mosquitoes may
      benefit from plasticity in their choice of egg-laying site as these sites are
      often temporally variable and clustered. The opportunity to adapt egg-laying
      behaviour to past experience also exists for mosquito populations as females
      typically lay eggs multiple times throughout their lives. Whether experience and
      age affect egg-laying (or oviposition) behaviour in the mosquito Stegomyia
      aegypti (=Aedes aegypti) (Diptera: Culicidae) was assessed using a wind tunnel.
      Initially, gravid mosquitoes were provided with a cup containing either repellent
      or well water. After ovipositing in these cups, the mosquitoes were blood-fed and
      introduced into a wind tunnel. In this wind tunnel, an oviposition cup containing
      repellent was placed in the immediate vicinity of the gravid mosquitoes. A cup
      containing well water was placed at the opposite end of the tunnel so that if the
      females flew across the chamber, they encountered the well water cup, in which
      they readily laid eggs. Mosquitoes previously exposed to repellent cups became
      significantly more likely to later lay eggs in repellent cups, suggesting that
      previous experience with suboptimal oviposition sites informs mosquitoes of the
      characteristics of nearby oviposition sites. These results provide further
      evidence that mosquitoes modify behaviour in response to environmental
      information and are demonstrated in a vector species in which behavioural
      plasticity may be ecologically and epidemiologically meaningful. 

PMID- 25982410
TI  - Protein Synthesis with Ribosomes Selected for the Incorporation of beta-Amino
      Acids.
AB  - In an earlier study, beta3-puromycin was used for the selection of modified
      ribosomes, which were utilized for the incorporation of five different beta-amino
      acids into Escherichia coli dihydrofolate reductase (DHFR). The selected
      ribosomes were able to incorporate structurally disparate beta-amino acids into
      DHFR, in spite of the use of a single puromycin for the selection of the
      individual clones. In this study, we examine the extent to which the structure of
      the beta3-puromycin employed for ribosome selection influences the regio- and
      stereochemical preferences of the modified ribosomes during protein synthesis;
      the mechanistic probe was a single suppressor tRNA(CUA) activated with each of
      four methyl-beta-alanine isomers (1-4). The modified ribosomes were found to
      incorporate each of the four isomeric methyl-beta-alanines into DHFR but
      exhibited a preference for incorporation of 3(S)-methyl-beta-alanine (beta-mAla;
      4), i.e., the isomer having the same regio- and stereochemistry as the O
      methylated beta-tyrosine moiety of beta3-puromycin. Also conducted were a
      selection of clones that are responsive to beta2-puromycin and a demonstration of
      reversal of the regio- and stereochemical preferences of these clones during
      protein synthesis. These results were incorporated into a structural model of the
      modified regions of 23S rRNA, which included in silico prediction of a H-bonding
      network. Finally, it was demonstrated that incorporation of 3(S)-methyl-beta
      alanine (beta-mAla; 4) into a short alpha-helical region of the nucleic acid
      binding domain of hnRNP LL significantly stabilized the helix without affecting
      its DNA binding properties.

PMID- 25982413
TI  - Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced
      synaptic plasticity gene expression changes and memory impairment.
AB  - The amnesic potential of scopolamine is well manifested through synaptic
      plasticity gene expression changes and behavioral paradigms of memory impairment.
      However, the underlying mechanism remains obscure and consequently ideal
      therapeutic target is lacking. In this context, chromatin-modifying enzymes,
      which regulate memory gene expression changes, deserve major attention.
      Therefore, we analyzed the expression of chromatin-modifying enzymes and recovery
      potential of enzyme modulators in scopolamine-induced amnesia. Scopolamine
      administration drastically up-regulated DNA methyltransferases (DNMT1) and HDAC2
      expression while CREB-binding protein (CBP), DNMT3a and DNMT3b remained
      unaffected. HDAC inhibitor sodium butyrate and DNMT inhibitor Aza-2'deoxycytidine
      recovered scopolamine-impaired hippocampal-dependent memory consolidation with
      concomitant increase in the expression of synaptic plasticity genes Brain-derived
      neurotrophic factor (BDNF) and Arc and level of histone H3K9 and H3K14
      acetylation and decrease in DNA methylation level. Sodium butyrate showed more
      pronounced effect than Aza-2'deoxycytidine and their co-administration did not
      exhibit synergistic effect on gene expression. Taken together, we showed for the
      first time that scopolamine-induced up-regulation of chromatin-modifying enzymes,
      HDAC2 and DNMT1, leads to gene expression changes and consequent decline in
      memory consolidation. Our findings on the action of scopolamine as an epigenetic
      modulator can pave a path for ideal therapeutic targets. We propose the following
      putative pathway for scopolamine-mediated memory impairment; scopolamine up
      regulates hippocampal DNMT1 and HDAC2 expression, induces methylation and
      deacetylation of BDNF and Arc promoter, represses gene expression and eventually
      impairs memory consolidation. On the other hand, Aza-2 and NaB inhibit DNMT1 and
      HDAC2 respectively, up-regulate BDNF and Arc expression and recover memory
      consolidation. We elucidate the action of scopolamine as an epigenetic modulator
      and hope that DNMT1 and HDAC2 would be ideal therapeutic targets for memory
      disorders.

PMID- 25982412
TI  - Transcranial direct current stimulation in obsessive-compulsive disorder:
      emerging clinical evidence and considerations for optimal montage of electrodes.
AB  - BACKGROUND: Neuromodulation techniques for obsessive-compulsive disorder (OCD)
      treatment have expanded with greater understanding of the brain circuits
      involved. Transcranial direct current stimulation (tDCS) might be a potential new
      treatment for OCD, although the optimal montage is unclear. OBJECTIVE: To perform
      a systematic review on meta-analyses of repetitive transcranianal magnetic
      stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to
      identify brain stimulation targets for future tDCS trials and to support the
      empirical evidence with computer head modeling analysis. METHODS: Systematic
      reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the
      tDCS computational analysis, we employed head models with the goal of optimally
      targeting current delivery to structures of interest. RESULTS: Only three
      references matched our eligibility criteria. We simulated four different
      electrodes montages and analyzed current direction and intensity. CONCLUSION:
      Although DBS, rTMS and tDCS are not directly comparable and our theoretical
      model, based on DBS and rTMS targets, needs empirical validation, we found that
      the tDCS montage with the cathode over the pre-supplementary motor area and extra
      cephalic anode seems to activate most of the areas related to OCD.

PMID- 25982414
TI  - GC-MS analysis of two types of mixed oils, a comparison of composition and
      weathering patterns.
AB  - In order to compare the effects of weathering on two types of mixed oil,
      simulated weathering experiments were performed. The first sample was a mixture
      of two fresh oils and the second sample was a mixture of one fresh oil and
      another oil sample that had undergone a serious weathering process. Comparative
      studies evaluated decay rates and changes in diagnostic ratios of some
      fingerprinting biomarkers. Results showed that the mixing process affected the
      weathering rate of some compounds in the oils and also that certain diagnostic
      ratios are more suitable for estimating mixing proportions. A Pr/n-C17 versus
      Ph/n-C18 plot can be used to identify the end-numbers of mixed oils and the
      (C13+C14)/(C25+C26) ratio is a useful diagnostic ratio to detect the degree of
      weathering. Finally, hopane, sterane, and alkylated PAH fingerprints were found
      to give useful insights about the sources of the mixed oils. 

PMID- 25982415
TI  - Environmental conditions influence tissue regeneration rates in scleractinian
      corals.
AB  - Natural and anthropogenic factors may influence corals' ability to recover from
      partial mortality. To examine how environmental conditions affect lesion healing,
      we assessed several water quality parameters and tissue regeneration rates in
      corals at six reefs around St. Thomas, US Virgin Islands. We hypothesized that
      sites closer to developed areas would have poor water quality due to proximity to
      anthropogenic stresses, which would impede tissue regeneration. We found that
      water flow and turbidity most strongly influenced lesion recovery rates. The most
      impacted site, with high turbidity and low flow, recovered almost three times
      slower than the least impacted site, with low turbidity, high flow, and low
      levels of anthropogenic disturbance. Our results illustrate that in addition to
      lesion-specific factors known to affect tissue regeneration, environmental
      conditions can also control corals' healing rates. Resource managers can use this
      information to protect low-flow, turbid nearshore reefs by minimizing sources of
      anthropogenic stress. 

PMID- 25982416
TI  - Exploring S1 plasticity and probing S1' subsite of mammalian aminopeptidase
      N/CD13 with highly potent and selective aminobenzosuberone inhibitors.
AB  - In order to probe the S1 and S1' mammalian aminopeptidase N subsites, racemic 1-
      or 4-substituted 7-aminobenzocyclohepten-6-one derivatives were synthesized and
      evaluated for their ability to inhibit mammalian aminopeptidase N. We focused on
      improving the physicochemical and ADME properties of this series by targeting
      lipophilicity and LELP score. Some 4-heteroaryl substituted analogues displayed
      reduced lipophilicity and enhanced inhibition potency with Ki values in the
      nanomolar range.

PMID- 25982417
TI  - A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids
      effects on inflammatory markers in colorectal cancer.
AB  - BACKGROUND: Cancer and inflammation are closely related and an exacerbated
      inflammatory process can lead to tumor progression and a worse prognosis for the
      patient with cancer. Scientific literature has shown evidence that n-3
      polyunsaturated fatty acids (PUFA) have anti-inflammatory action, and for this
      reason could be useful as an adjuvant in the treatment of some cancers.
      OBJECTIVE: A systematic review and meta-analysis of the literature was conducted
      until September, 2014, to evaluate the effects of n-3 PUFA on inflammatory
      mediators in colorectal cancer (CRC) patients. PATIENTS AND METHODS: Clinical
      trials were systematically searched in three electronic databases and screening
      reference lists. Random meta-analysis model was used to calculate the overall and
      stratified effect sizes. RESULTS: Nine trials, representing 475 patients with
      CRC, evaluated effects of n-3 PUFA on cytokines (n = 6) and/or acute phase
      proteins (n = 5) levels. n-3 PUFA reduce the levels of IL-6 (SMD -2.34; 95% CI 
      4.37, -0.31; p = 0.024) and increase albumin (SMD 0.31; 95% CI 0.06, 0.56; p =
      0.014) in overall analyses. In stratified analyses, reduction in IL-6 levels
      occurs in surgical patients that received 0.2 g/kg of fish oil parenterally at
      postoperative period (SMD -0.65; 95% CI -1.06, -0.24; p = 0.002), while, increase
      in albumin concentration occurs in surgical patients that received >= 2.5 g/d of
      EPA + DHA orally at preoperative period (SMD 0.34; 95% CI 0.02, 0.66; p = 0.038).
      In patients undergoing chemotherapy, the supplementation of 0.6 g/d of EPA + DHA
      during 9 week reduces CRP levels (SMD -0.95; 95% CI -1.73, -0.17; p = 0.017), and
      CRP/albumin ratio (SMD -0.95; 95% CI -1.73, -0.18; p = 0.016). CONCLUSIONS: The
      results suggest benefits on some inflammatory mediators with the use of n-3 PUFA
      on CRC patients, but these benefits are specific to certain supplementation
      protocols involving duration, dose and route of administration, and also, the
      concomitant anti-cancer treatment adopted.

PMID- 25982418
TI  - Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal
      in Iminium Ion Activation.
AB  - Substituting N-methylpyrrole for N-methyindole in secondary-amine-catalysed
      Friedel-Crafts reactions leads to a curious erosion of enantioselectivity. In
      extreme cases, this substrate dependence can lead to an inversion in the sense of
      enantioinduction. Indeed, these closely similar transformations require two
      structurally distinct catalysts to obtain comparable selectivities. Herein a
      focussed molecular editing study is disclosed to illuminate the structural
      features responsible for this disparity, and thus identify lead catalyst
      structures to further exploit this selectivity reversal. Key to effective
      catalyst re-engineering was delineating the non-covalent interactions that
      manifest themselves in conformation. Herein we disclose preliminary validation
      that intermolecular aromatic (CH-pi and cation-pi) interactions between the
      incipient iminium cation and the indole ring system is key to rationalising
      selectivity reversal. This is absent in the N-methylpyrrole alkylation, thus
      forming the basis of two competing enantio-induction pathways. A simple L-valine
      catalyst has been developed that significantly augments this interaction. 

PMID- 25982419
TI  - Molecular identification of Botrytis cinerea, Botrytis paeoniae and Botrytis
      pseudocinerea associated with gray mould disease in peonies (Paeonia lactiflora
      Pall.) in Southern Chile.
AB  - BACKGROUND: In Chile, the peony is the most important ornamental flower exported
      from the country. Gray mould is a phytopathological problem of this crop. This
      disease is caused by Botrytis cinerea and Botrytis paeoniae. AIMS: We carried out
      the first survey of Botrytis species associated with peony gray mould in Southern
      Chile to estimate the diversity of these pathogens. METHODS: Diseased peony
      leaves were collected from seven locations in Southern Chile covering a distance
      of 300km. The Botrytis isolates obtained were studied by morphological and
      molecular methods. Finally, a PCR assay using primers based on the necrosis and
      ethylene-inducing protein gene (nep1) was used to specifically identify B.
      paeoniae. RESULTS: Seventeen isolates belonging to Botrytis genus were obtained,
      and all of them were pathogenic to peonies when inoculated in plants grown in a
      greenhouse. Morphological analyses showed that four isolates shared common
      characteristics, which distinguish them from the rest. Homology and phylogenetic
      analysis of G3PDH, as well as determination of the Bc-hch allele, allowed us to
      identify 12 isolates as B. cinerea, 4 as B. paeoniae and one isolate as Botrytis
      pseudocinerea. The PCR assay was found to be specific to B. paeoniae, amplifying
      a single band of 470bp. CONCLUSIONS: Three Botrytis species involved in peony
      gray mould disease are present in Chile. This is the first time that both B.
      paeoniae and B. pseudocinerea have been reported to be present in the country and
      also that they affect peonies. Finally, to our knowledge, the PCR based method
      herein described is the first of its kind to be used to identify B. paeoniae.

PMID- 25982420
TI  - Cytotoxic activity and induction of inflammatory mediators of the
      methanol:chloroform extract of Fusarium moniliforme.
AB  - BACKGROUND: Fusarium moniliforme is a phytopathogenic facultative fungus with a
      cosmopolitan distribution in all types of climates, and has a wide host range,
      including, among others, bean, rice, wheat and sorghum crops. There is a current
      lack of knowledge regarding the potential of these fungi, so it is considered to
      be of great importance to obtain information related to the biological activity
      of extracts and secondary metabolites. AIMS: An evaluation of the role of
      methanol:chloroform extract of F. moniliforme in the production of inflammatory
      cytokines and their cytotoxic activity. METHODS: The production of nitric oxide
      was analyzed by the Griess method, the production of cytokines using ELISA, and
      the effects of the extract on cell cycle and induction of apoptosis by flow
      cytometry. RESULTS: The extract of F. moniliforme was seen to be able to
      stimulate nitric oxide (NO) production in J774A.1 cells, as well as to produce
      cytokines such as, IL-1beta, IL-6, and TNF-alpha. It was also observed that the
      extract of F. moniliforme produces activity on cell cycle modulation and
      apoptosis when tested in carcinogenic cell lines. CONCLUSIONS: The results
      obtained from this study open the possibility of obtaining and identifying
      metabolites of the extract of F. moniliforme that can be evaluated for possible
      use in cancer therapy.

PMID- 25982421
TI  - Proper use of medical language: Main problems and solutions.
AB  - Medical language should be characterized by its precision, emotional neutrality
      and stability. The effective communication of results of scientific studies
      depends on compliance with current standards of drafting and style; texts with
      defects can hinder interest in the findings. In this study, we discuss some of
      the most common problems and errors in medical language, including the abuse of
      abbreviations and foreign words, the use of improper words, syntax errors and
      solecisms, the most common errors in titles and the abuse of capital letters and
      the gerund. Investigators have effective tools for dealing with these problems,
      such as quality texts, critical dictionaries of questions and difficulties with
      the Spanish language and various drafting and style manuals. 

PMID- 25982422
TI  - Ovarian hyperstimulation syndrome after gonadotropin-releasing hormone agonist
      triggering and "freeze-all": in-depth analysis of genetic predisposition.
AB  - PURPOSE: We report on the results of the whole-genome analysis performed in a
      patient who developed severe ovarian hyperstimulation syndrome (OHSS) following
      gonadotropin-releasing hormone (GnRH) agonist triggering in a "freeze-all"
      protocol. METHODS: A 30-year-old patient with polycystic ovary syndrome who
      developed severe early-onset OHSS with clinical ascites, and slight renal and
      hepatic dysfunction was admitted for monitoring and treatment with cabergoline
      and intravenous albumin. Exome sequencing to assess for any known genetic
      predisposition for OHSS was performed. RESULTS: No known genetic variants
      associated with OHSS predisposition were found. CONCLUSIONS: Case reports of
      severe OHSS following a "freeze-all" strategy are starting to arise, showing that
      OHSS has not been completely eliminated with this approach. Further studies
      should be conducted to confirm if such cases may be due to genetic predisposition
      or not.

PMID- 25982423
TI  - Rescue intra-arterial chemotherapy following retinoblastoma recurrence after
      initial intra-arterial chemotherapy.
AB  - PURPOSE: To determine the efficacy of rescue intra-arterial chemotherapy (IAC)
      for retinoblastoma recurrence following failed initial IAC. METHODS:
      Retrospective, non-comparative, interventional case series of 12 eyes in 12
      patients. INTERVENTION: Rescue IAC employed chemotherapy agents of melphalan
      (5mg, 7.5mg) alone or with additional topotecan (1mg). MAIN OUTCOME MEASURE:
      Tumor control and globe salvage. RESULTS: The median patient age at initial
      presentation was 16 months. At initial examination, the International
      Classification of Retinoblastoma grouping was group B (n=1), group D (n=7), or
      group E (n=4). The initial IAC was primary in 5 cases (42%) and secondary
      following failure of intravenous chemotherapy in 7 (58%). In all cases, initial
      IAC was delivered using melphalan 3mg (n=3), melphalan 5mg (n=7), or combination
      melphalan 5mg/topotecan 1mg (n=2) for a median of 3 cycles. The mean interval
      from initial IAC to recurrence necessitating rescue IAC was 5 months (median 4,
      range 2-10 months). Of the 12 patients, 3 (25%) had undergone previous
      enucleation of the opposite eye and the rescue IAC was planned for the only
      remaining eye. Rescue IAC was delivered for recurrent solid tumor (n=1),
      recurrent subretinal seeds (n=7), recurrent vitreous seeds (n=1), or combination
      recurrent subretinal/vitreous seeds (n=3). IAC was technically successful through
      the ophthalmic artery in 9 cases (75%) or the middle meningeal artery in 3 (25%).
      Rescue IAC involved median 3 cycles (mean 3, range 2-4 cycles) of higher dose
      melphalan in 4 cases (33%) or combination melphalan/topotecan in 8 (67%). At mean
      follow-up of 20 months (median 14 months, range 7-36 months), complete tumor
      control was achieved in 9 eyes (75%) and globe salvage in 8 eyes (67%). Of the 3
      failure eyes, all were initially groups D or E, previously treated with initial
      IAC, and 2 had previous intravenous chemotherapy. There were 4 eyes that came to
      enucleation for persistent subretinal/vitreous seeds (n=3) or neovascular
      glaucoma without viable tumor (n=1). There was no case of cerebrovascular stroke,
      systemic metastasis, or death. CONCLUSION: Rescue IAC following retinoblastoma
      recurrence after initial IAC provided tumor control in 75% of cases and globe
      salvage in 67%. Rescue IAC can be considered in children who fail initial IAC,
      especially if the opposite eye has been enucleated.

PMID- 25982425
TI  - [Bacterial flora in blepharitis].
AB  - INTRODUCTION: Blepharitis has multiple, poorly defined origins. The goal of this
      study was to investigate the bacterial flora present in patients affected with
      blepharitis in comparison with healthy subjects, so as to understand the role of
      bacterial etiologies in blepharitis. MATERIALS AND METHODS: Fifty-four patients
      with blepharitis and 50 healthy controls participated in this study. Swabs were
      obtained and analyzed qualitatively and quantitatively for bacteria. A subgroup
      of 16 people (9 with blepharitis and 7 controls) also were investigated for
      Demodex. RESULTS: The percentages of the positive cultures and the number of
      colonies/case were clearly higher for patients with blepharitis in comparison
      with healthy controls. Bacteria were isolated for 81% of cases versus 38% for
      controls, with a mean of 39 colonies versus 4.4 colonies for controls.
      Corynebacterium sp. were the most common microorganisms isolated from patients
      with blepharitis (53.7% for cases versus 18% for controls, P<0.01), and the
      bacterial load was 15 times higher (37.4 col/case versus 2.6 col/case). C.
      macginleyi was the most common Corynebacteria (33% versus 6%, P<0.01). S.
      epidermidis: 35.1% versus 16% (P=0.02) with 11.3 col/case versus 1.6 col/case. S.
      aureus: 13% versus 0% (P=0.01) with 24.7 col/case versus 0. We did not find a
      significant difference for Propionibacterium acnes: 14.8% versus 14% with 4.7
      col/case versus 5.1 col/case, or for Demodex, with 22.2% versus 28.6%.
      CONCLUSION: Corynebacterium sp. and especially C. macginleyi seem to participate
      actively in the physiopathology of blepharitis. S. epidermidis and S. aureus also
      remain associated with this pathology.

PMID- 25982424
TI  - Socioeconomic and psychological impact of treatment for unilateral intraocular
      retinoblastoma.
AB  - PURPOSE: To identify the socioeconomic and psychosocial impacts of clinical
      treatment decisions for advanced unilateral intraocular retinoblastoma. DESIGN:
      Retrospective observational case series. METHODS:  SETTING: institutional study
      at Alexandria Main University Hospital. STUDY POPULATION: records of 66
      unilateral retinoblastoma cases treated from May 2005 to May 2013 were
      retrospectively reviewed. Sixty cases were eligible (International Intraocular
      Retinoblastoma Classification [IIRC] group C, D or E). PROCEDURES: two treatment
      groups were compared: enucleation vs. salvage treatment. Salvage treatment eyes
      were further subdivided based on IIRC group. Six socioeconomic parameters
      (financial burden, financial impact, psychological, social, medical and tumor
      impacts) were scored. Parameter scores ranged from 0 to 3, for overall score
      range 0 (no adverse impact) to 18 (severe adverse impact). MAIN OUTCOME MEASURES:
      derived Socioeconomic scores were correlated with treatment and outcomes.
      RESULTS: The enucleation group (28 eyes) had a median overall Socioeconomic score
      of 4/18, significantly lower than the salvage treatment group (32 eyes), median
      score 11/18 (P<0.01). Socioeconomic score varied with IIRC group. Attempted eye
      salvage failed in 25 children, due to uncontrolled tumor (44%) and socioeconomic
      impact of cumulative therapies (56%). Treatment duration and Socioeconomic score
      were higher for the 5 children in the salvage treatment group who developed
      metastatic disease compared to those without metastasis (P<0.01). CONCLUSIONS:
      The socioeconomic and psychosocial impacts of attempted ocular salvage for
      unilateral intraocular retinoblastoma are severe, in comparison to primary
      enucleation. Primary enucleation is a good treatment for unilateral
      retinoblastoma.

PMID- 25982426
TI  - Antimicrobial Susceptibility-Guided Therapy Versus Empirical Concomitant Therapy
      for Eradication of Helicobacter pylori in a Region with High Rate of
      Clarithromycin Resistance.
AB  - BACKGROUND: Nonbismuth quadruple (concomitant) regimen is recommended for first
      line empirical Helicobacter pylori (HP) eradication treatment when clarithromycin
      resistance is more than 15-20%. Our objective was to evaluate the efficacy and
      tolerability of concomitant versus antimicrobial susceptibility-guided treatment
      in an area with high rates of clarithromycin resistance. METHODS: Three hundred
      consecutive HP-infected patients received antimicrobial susceptibility-guided
      therapy or empirical concomitant therapy for 10 days. The concomitant regimen was
      omeprazole (20 mg/12 hour), amoxicillin (1 g/12 hour), clarithromycin (500 mg/12
      hour), and metronidazole (500 mg/12 hour) (OACM). Patients diagnosed by culture
      received one of three combinations of antibiotics based on susceptibility
      results: omeprazole, amoxicillin, and clarithromycin (OAC); omeprazole,
      amoxicillin, and levofloxacin (OAL); or omeprazole, amoxicillin, and
      metronidazole (OAM), at the aforementioned doses (and 500 mg/12 hour in the case
      of levofloxacin). Eradication was confirmed with a (13)C urea breath test, 6
      weeks after treatment. Adverse events and adherence were assessed with
      questionnaires and reviewing medication sachets. RESULTS: The mean age was 50
      years, 59% were women, and 14% had peptic ulcers. Concomitant and antimicrobial
      susceptibility-guided eradication rates were, respectively, 87% and 94% by
      intention-to-treat (p = .08) and 89% and 95% (p = .08) per protocol per-protocol
      analysis. Adverse effects were reported in 31% of patients on OACM and 15% of
      those on susceptibility-guided therapy (p < .05). CONCLUSIONS: For HP eradication
      in a region with high rates of multiple drug resistance, antimicrobial
      susceptibility-guided therapy is more effective than empirical concomitant
      therapy.

PMID- 25982427
TI  - Direct ophthalmoscopy: teaching in primary care.

PMID- 25982428
TI  - Predicting risk of entry into foster care from early childhood experiences: A
      survival analysis using LONGSCAN data.
AB  - This study examined whether a multi-domain model of maltreatment informed by an
      ecological framework-including factors related to the child, caregiver, family,
      neighborhood, and dimensions of maltreatment experience-predicted entry into
      foster care between the ages of 4 and 18 among children with no prior foster care
      experience. To determine which factors predict entry into foster care, secondary
      data analyses were conducted utilizing a sub-sample from LONGSCAN (Longitudinal
      Studies of Child Abuse and Neglect) of 942 children and their primary caregivers.
      Results demonstrate that there are important predictors for entry into out-of
      home placement across multiple ecological domains. Characteristics related to
      child, caregiver, and family characteristics, and neighborhood context, as well
      as dimensions of maltreatment (particularly emotional maltreatment), predicted
      risk of placement in out-of-home care. Implications for child welfare practice
      are discussed. This examination of the effects of multiple ecological domains
      adds to our understanding of children's risk of removal and entry into out-of
      home placement. 

PMID- 25982430
TI  - Pseudoarthrosis rates in anterior cervical discectomy and fusion: a meta
      analysis.
AB  - BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is a commonly
      performed procedure for patients presenting with cervical radiculopathy,
      myelopathy, or deformity. A systematic literature review and meta-analysis of
      pseudoarthrosis rates associated with ACDF with plate fixation have not been
      previously performed. PURPOSE: The purpose of this study was to identify all
      prospective studies reporting pseudoarthrosis rates for ACDF with plate fixation.
      STUDY DESIGN/SETTING: This study is based on a systematic review and meta
      analysis. PATIENT SAMPLE: Studies reporting pseudoarthrosis rates in patients who
      received one-, two-, or three-level ACDF surgeries were included. OUTCOME
      MEASURES: Outcomes of interest included reported pseudoarthrosis events after
      ACDF with plate fixation. METHODS: We conducted a MEDLINE, SCOPUS, Web of
      Science, and EMBASE search for studies reporting complications for ACDF with
      plate fixation. We recorded pseudoarthrosis events from all included studies. A
      meta-analysis was performed to calculate effect summary mean values, 95%
      confidence intervals (CIs), Q statistics, and I(2) values. Forest plots were
      constructed for each analysis group. RESULTS: Of the 7,130 retrieved articles, 17
      met the inclusion criteria. The overall pseudoarthrosis rate was 2.6% (95% CI:
      1.3-3.9). Use of autograft fusion (0.9%, 95% CI: -0.4 to 2.1) resulted in a
      reduced pseudoarthrosis rate compared with allograft fusion procedures (4.8%, 95%
      CI: 1.7-7.9). Studies were separated based on the length of follow-up: 12 to 24
      and greater than 24 months. These groups reported rates of 3.1% (95% CI: 1.2-5.0)
      and 2.3% (95% CI: 0.1-4.4), respectively. Studies performing single-level ACDF
      yielded a rate of 3.7% (95% CI: 1.6-5.7). Additionally, there was a large
      difference in the rate of pseudoarthrosis in randomized controlled trials (4.8%,
      95% CI: 2.6-7.0) versus prospective cohort studies (0.2%, 95% CI: -0.1 to 0.5),
      indicating that the extent of follow-up criteria affects the rate of
      pseudoarthrosis. CONCLUSIONS: This review represents a comprehensive estimation
      of the actual incidence of pseudoarthrosis across a heterogeneous group of
      surgeons, patients, and ACDF techniques. The definition of pseudoarthrosis varied
      significantly within the literature. To ensure its diagnosis and prevent
      sequelae, standardized criteria need to be established. This investigation sets
      the framework for surgeons to understand the impact of surgical techniques on the
      rate of pseudoarthrosis.

PMID- 25982431
TI  - Thoracic paraspinal desmoid-type fibromatosis.

PMID- 25982432
TI  - Rare complication of Chiari Type 1 malformation: cervical kyphosis.

PMID- 25982429
TI  - Nuclear transport factors: global regulation of mitosis.
AB  - The unexpected repurposing of nuclear transport proteins from their function in
      interphase to an equally vital and very different set of functions in mitosis was
      very surprising. The multi-talented cast when first revealed included the import
      receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a
      subset of nuclear pore proteins. In this review, we report that recent years have
      revealed new discoveries in each area of this expanding story in vertebrates: (a)
      The cast of nuclear import receptors playing a role in mitotic spindle regulation
      has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an
      export receptor, are involved in different aspects of spindle assembly. Importin
      beta and transportin also regulate nuclear envelope and pore assembly. (b) The
      role of nucleoporins has grown to include recruiting the key microtubule
      nucleator - the gamma-TuRC complex - and the exportin Crm1 to the mitotic
      kinetochores of humans. Together they nucleate microtubule formation from the
      kinetochores toward the centrosomes. (c) New research finds that the original
      importin beta/RanGTP team have been further co-opted by evolution to help
      regulate other cellular and organismal activities, ranging from the actual
      positioning of the spindle within the cell perimeter, to regulation of a newly
      discovered spindle microtubule branching activity, to regulation of the
      interaction of microtubule structures with specific actin structures. (d) Lastly,
      because of the multitudinous roles of karyopherins throughout the cell cycle, a
      recent large push toward testing their potential as chemotherapeutic targets has
      begun to yield burgeoning progress in the clinic. 

PMID- 25982433
TI  - A rare cause of back pain: simple bone cyst in the lumbar vertebra.

PMID- 25982434
TI  - Spinal intramedullary metastasis as the first manifestation of lung cancer.

PMID- 25982435
TI  - A rare case of thoracolumbar aspergillosis involving T10-L5.

PMID- 25982436
TI  - Extranodal non-Hodgkin's lymphoma with multiple vertebral and hepatic lesions
      without involvement of lymph nodes.

PMID- 25982437
TI  - A rare case of atypical noncontiguous multiple spinal tuberculosis.

PMID- 25982438
TI  - Multiple spinal myxopapillary ependymomas presented with back pain.

PMID- 25982439
TI  - Dorsal transdural migration of a sequestered intradural lumbar disc.

PMID- 25982440
TI  - Spinal metastasis of medulloblastoma in adults.

PMID- 25982441
TI  - The large scale antibacterial, antifungal and anti-phage efficiency of Petamcin
      A: new multicomponent preparation for skin diseases treatment.
AB  - BACKGROUND: Human and animal skin diseases of bacterial, fungal and viral nature
      and their complications are widespread and globally cause a serious trouble.
      Their prevalence is increasing mainly due to drug resistance. Consequently,
      demand has increased for new effective antimicrobial drugs, which also should be
      less toxic, possess a wider spectrum of action and be economically more
      beneficial. The goal was to investigate antibacterial, antifungal and anti-phage
      activity of Petamcin-A-a new multicomponent preparation. It contains acetic acid
      and hexamethylenetetramine as main active antimicrobial components, as well as
      phosphatidylcholine, tocopheryl acetate and glycerol as excipients. METHODS:
      Bacteriostatic activity and minimal inhibitory concentrations of the preparation
      against various test-organisms were determined by agar well diffusion assay.
      Antifungal activity was tested by agar dilution assay. To explore anti-phage
      activity double agar overlay plaque assay was used. Nystatin, chlorhexidine and
      acetic acid were used as control agents for comparative analysis. Statistical
      analysis was done with GraphPad Prism 5.03 or R 3.1.0 software. RESULTS: The
      results showed a higher activity of Petamcin-A against all bacterial and fungal
      test strains compared with its components or control agents. The preparation was
      more effective against tested gram-positive bacteria than gram-negative ones.
      Petamcin-A expressed bactericidal activity against almost all test strains. In
      addition, the preparation demonstrated high activity against T4 phage of
      Escherichia coli C-T4 completely inhibiting its growth. 5-fold diluted Petamcin-A
      also exhibited considerable activity reducing phage concentration by 2.6 Log10.
      CONCLUSIONS: Petamcin-A has a high antimicrobial activity against all tested
      strains of bacteria, yeasts and moulds. The preparation also exhibited high anti
      phage activity. Moreover, taking into account that Petamcin-A has no observable
      toxicity on skin and its components are not expensive, it can be advantageous for
      management of various skin medical conditions.

PMID- 25982442
TI  - Foam-like compression behavior of fibrin networks.
AB  - The rheological properties of fibrin networks have been of long-standing
      interest. As such there is a wealth of studies of their shear and tensile
      responses, but their compressive behavior remains unexplored. Here, by
      characterization of the network structure with synchronous measurement of the
      fibrin storage and loss moduli at increasing degrees of compression, we show that
      the compressive behavior of fibrin networks is similar to that of cellular
      solids. A nonlinear stress-strain response of fibrin consists of three regimes:
      (1) an initial linear regime, in which most fibers are straight, (2) a plateau
      regime, in which more and more fibers buckle and collapse, and (3) a markedly
      nonlinear regime, in which network densification occurs by bending of buckled
      fibers and inter-fiber contacts. Importantly, the spatially non-uniform network
      deformation included formation of a moving "compression front" along the axis of
      strain, which segregated the fibrin network into compartments with different
      fiber densities and structure. The Young's modulus of the linear phase depends
      quadratically on the fibrin volume fraction while that in the densified phase
      depends cubically on it. The viscoelastic plateau regime corresponds to a mixture
      of these two phases in which the fractions of the two phases change during
      compression. We model this regime using a continuum theory of phase transitions
      and analytically predict the storage and loss moduli which are in good agreement
      with the experimental data. Our work shows that fibrin networks are a member of a
      broad class of natural cellular materials which includes cancellous bone, wood
      and cork. 

PMID- 25982444
TI  - Challenges of pastoral cattle production in a sub-humid zone of Nigeria.
AB  - PURPOSE: More than 80 % of the 20 million heads of Nigerian cattle are kept by
      pastoral households. As such, optimal herd management is important in maintaining
      human nutrition, livelihoods and socio-cultural balance. This study was conducted
      to contribute to discussions on emerging challenges of the Nigerian livestock
      sector and to estimate herd prevalence, relative incidence, case fatality and
      impact on livelihood of cattle diseases in pastoral areas. METHODS: Participatory
      epidemiological approaches: listing; pairwise ranking; proportional piling;
      matrix scoring and probing were used to collect data through focus group
      interviews with Fulani herdsmen from selected pastoral areas of the country.
      RESULTS: The main cattle production problems were as follows: conversion of land
      used for cattle routes into crop fields, cattle rustling and water scarcity with
      median scores for impact on livelihood being 19, 17 and 16%, respectively. Animal
      diseases were fourth in the list of problems, and diseases reported to have
      significant impacts on livelihood were trypanosomiasis (25%), contagious bovine
      pleuropneumonia (15%), foot and mouth disease (13%) and fascioliasis (13%). High
      relative incidence rates were reported for trypanosomiasis (27%), fascioliasis
      (24%) and foot and mouth disease (19%). CONCLUSION: Change of land use and
      rustling indicate weaknesses in the producers' institutional environments. Water
      scarcity, limited access to veterinary services and substandard drugs supplied by
      vendors were identified as key factors contributing to persistence and frequent
      outbreaks of diseases. The paper revealed a greater importance of land
      constraints and rustling relative to disease and highlighted policy issues on
      management of natural resources and livestock development given challenges
      associated with pastoralism and insecurity in Nigeria.

PMID- 25982443
TI  - Feeding behavior of feedlot-finished young bulls fed diets containing peanut
      cake.
AB  - The objective of this study was to evaluate the feeding behavior of feedlot
      finished young bulls fed diets containing peanut cake instead of soybean meal. A
      total of 32 Nellore young bulls with an initial body weight of 390 +/- 43.5 kg
      were distributed in a completely randomized design. The animals were individually
      housed in stalls and fed Tifton 85 hay with four concentrate mixtures containing
      0, 33, 66, or 100% peanut cake substituting for soybean meal. The diets were
      formulated to be isonitrogenous (with 15% crude protein) and isocaloric (with 65%
      total digestible nutrients), with a 40:60 forage:concentrate ratio, in the form
      of total mixed diet. The experimental period was 90 days, and data were collected
      every 28 days. Feeding behavior was assessed by means of observation and
      recording of the daily time spent feeding, ruminating, and idling, quantification
      of the periods and calculation of variables related to mastication
      characteristics as well as feeding and rumination efficiencies. Substitution of
      soybean meal for peanut cake in the diets caused a linear decrease in the intake
      of dry matter and neutral detergent fiber but did not affect the behavioral
      activities of the young bulls. Peanut cake may therefore replace up to 100% of
      soybean meal in the diet of feedlot-finished young Nellore bulls because it does
      not affect the feeding behavior of these animals.

PMID- 25982445
TI  - Monte Carlo calculations of the HPGe detector efficiency for radioactivity
      measurement of large volume environmental samples.
AB  - A fully detailed Monte Carlo geometrical model of a High Purity Germanium
      detector with a (152)Eu source, packed in Marinelli beaker, was developed for
      routine analysis of large volume environmental samples. Then, the model
      parameters, in particular, the dead layer thickness were adjusted thanks to a
      specific irradiation configuration together with a fine-tuning procedure.
      Thereafter, the calculated efficiencies were compared to the measured ones for
      standard samples containing (152)Eu source filled in both grass and resin
      matrices packed in Marinelli beaker. From this comparison, a good agreement
      between experiment and Monte Carlo calculation results was obtained highlighting
      thereby the consistency of the geometrical computational model proposed in this
      work. Finally, the computational model was applied successfully to determine the
      (137)Cs distribution in soil matrix. From this application, instructive results
      were achieved highlighting, in particular, the erosion and accumulation zone of
      the studied site. 

PMID- 25982446
TI  - Molecular dynamics simulations of the transport of reactive oxygen species by
      mammalian and plant aquaporins.
AB  - BACKGROUND: Aquaporins are responsible for water transport across lipid
      membranes. They are also able to transport reactive oxygen species, playing an
      important role in redox signaling. Certain plant aquaporins have even the ability
      to be regulated by oxidative stress. However, the underlying mechanisms are still
      not fully understood. METHODS: Here, molecular dynamics simulations were employed
      to determine the activation free energies related to the transport of reactive
      oxygen species through both mammalian and plant aquaporin models. RESULTS AND
      CONCLUSIONS: Both aquaporins may transport hydrogen peroxide (H2O2) and the
      protonated form of superoxide radicals (HO2). The solution-to-pore transfer free
      energies were low for small oxy-radicals, suggesting that even highly reactive
      hydroxyl radicals (HO) might have access to the pore interior and oxidize amino
      acids responsible for channel selectivity. In the plant aquaporin, no significant
      change in water permeability was observed upon oxidation of the solvent-exposed
      disulfide bonds at the extracellular region. During the simulated time scale, the
      existence of a direct oxidative gating mechanism involving these disulfide bonds
      could not be demonstrated. GENERAL SIGNIFICANCE: Simulation results may improve
      the understanding of redox signaling mechanisms and help in the interpretation of
      protein oxidative labeling experiments.

PMID- 25982448
TI  - Outcome and risk factor analysis of patients who underwent open infrarenal aortic
      aneurysm repair.
AB  - INTRODUCTION: The aim of this study was to evaluate the short- and long-term
      outcomes in patients who underwent open infrarenal aortic aneurysm repair.
      METHODS: Consecutive patients who underwent open repair of infrarenal aortic
      aneurysms at our institution from July 1(st) 1990 to June 30(th) 2012 were
      reviewed from a prospective collected departmental database. Short-term outcomes
      included 30-day mortality and peri-operative complications. Independent risk
      factors to predict 30-day mortality were identified. Long-term survival and
      secondary interventions were also reported. RESULTS: Three hundred and eighty
      three patients (317 males, median age 72 years with a range of 15-90 years)
      underwent open infrarenal aortic aneurysm repair during the period, of whom 266
      (69.5%) were elective, 18 (4.7%) were urgent for symptomatic but nonruptured
      cases, and 99 (25.8%) were emergency procedures for ruptured aneurysms. Mean
      aneurysm size was 6.5 cm (ranging from 2.5 cm to15 cm). All patients were
      followed up for at least 24 months with a mean follow up period 163 months.
      Overall 30-day mortality was 11.0% (36.4% for ruptured cases, 11.1% for
      symptomatic cases, and 1.5% for elective cases; p < 0.001). Preexisting renal
      disease and ruptured aneurysms were independent risk factors for 30-day mortality
      (p = 0.001 and p = 0.006 respectively). Systemic complications included 50
      cardiac events, 52 respiratory events, six renal events, three cerebral vascular
      accidents, and one deep vein thrombosis/pulmonary embolism. Local complications
      included two anastomotic/graft hemorrhage, 10 distal thrombosis/embolisms, five
      bowel ischemias, one spinal cord ischemia, and 17 wound complications. The
      ruptured group presented survival rates of 53.5%, 50.5%, 47.5%, 42.3%, 38.0%,
      21.9%, and 12.5% at 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, and 15
      years, respectively; while nonruptured survival rates were 91.5%, 88.0%, 83.7%,
      78.3%, 73.0%, 43.0%, and 25.3%, respectively (log rank p < 0.001). For those who
      died 30 days after the operation, only six patients (1.8%) died from aneurysm
      related mortality. A total of three (0.9%) patients underwent late re
      interventions, one for late aorto-enteric fistulae and two for anastomotic
      pseudoaneurysms. CONCLUSION: In the current era of endovascular repair, open
      infrarenal aneurysm repair is effective and durable, and has very low secondary
      interventions rates.

PMID- 25982447
TI  - MicroRNA-19a regulates lipopolysaccharide-induced endothelial cell apoptosis
      through modulation of apoptosis signal-regulating kinase 1 expression.
AB  - BACKGROUND: MicroRNAs, small non-encoding RNAs that post-transcriptionally
      modulate expression of their target genes, have been implicated as critical
      regulatory molecules in endothelial cells. RESULTS: In the present study, we
      found that overexpression of miR-19a protects endothelial cells from
      lipopolysaccharide (LPS)-induced apoptosis through the apoptosis signal
      regulating kinase 1 (ASK1)/p38 pathway. Quantitative real-time PCR demonstrated
      that the expression of miR-19a in endothelial cell was markedly down-regulated by
      LPS stimulation. Furthermore, LPS-induced apoptosis was significantly inhibited
      by over-expression of miR-19a. Finally, both a luciferase reporter assay and
      western blot analysis showed that ASK1 is a direct target of miR-19a.
      CONCLUSIONS: MiR-19a regulates ASK1 expression by targeting specific binding
      sites in the 3' untranslated region of ASK1 mRNA. Overexpression of miR-19a is an
      effective method to protect against LPS-induced apoptosis of endothelial cells.

PMID- 25982449
TI  - Is LigaSure a safe cystic duct sealer? An ex vivo study.
AB  - BACKGROUND: To compare the efficacy and safety of both mechanical methods (clips)
      and electrosurgical instruments, harmonic scalpel (HS) and LigaSure (LS), for
      securing the cystic duct during laparoscopic cholecystectomy (LC). METHODS:
      During the study period from October 2010 to October 2012, 458 patients with
      gallbladder stones underwent LC. A total of 38 patients were excluded from the
      study for different reasons. The gallbladder was excised laparoscopically through
      the traditional method. The gallbladder specimens of the patients were divided
      into three equal groups randomly, and the distal part of the cystic duct was
      sealed ex vivo using ligaclips (Group A), HS (Group B), and LS (Group C). The
      gallbladders were then connected to a pneumatic tourniquet device and we very
      gradually increased the pressure with air. The bursting pressure of the cystic
      duct (CDBP) was measured and differences between the three groups were
      calculated. RESULTS: The mean CDBP was 329.7 +/- 38.8 mmHg in the ligaclip group,
      358.0 +/- 33.1 mmHg in the HS group, and 219.7 +/- 41.2 mmHg in the LS group. A
      comparison of the mean CDBP between the groups indicated the superiority of HS
      over ligaclip and LS. CDBP was significantly higher in the ligaclips group
      compared with the LS group (p <0.001). HS and ligaclips were found to be safe
      sealers as their mean CDBP was found to be higher (>195 mmHg) than the maximum
      common bile duct pressure, whereas for LS the CDBP range was 150-297 mmHg,
      indicating that it is not safe for sealing. CONCLUSION: HS is a safe alternative
      to clips. In fact, it was even safer than clips. By contrast, LS is not safe for
      cystic duct sealing.

PMID- 25982450
TI  - Gliotoxin production by Aspergillus fumigatus strains from animal environment.
      Micro-analytical sample treatment combined with a LC-MS/MS method for gliotoxin
      determination.
AB  - In this study, gliotoxin production by Aspergillus fumigatus strains from animal
      environment is studied. Moreover, a rapid, easy and environment-friendly micro
      analytical sample treatment procedure coupled with LC-MS/MS was applied for the
      determination of gliotoxin from A. fumigatus cultures. The ability of gliotoxin
      production by 143 strains was assayed in yeast extract sucrose agar, and 1 ml of
      chloroform was used for toxin extraction without further clean-up. Mean
      recoveries at two spiking levels (2500 and 7000 ng/g; n = 6) were 100.3 +/- 6.6 %
      relative SD (RSD) and 92.4 +/- 3.8 % RSD. Repeatability and within-laboratory
      reproducibility for different concentration levels of gliotoxin (25 to 1000
      ng/ml; n = 12) ranged from 0.3 to 5.4 % RSD and from 3.9 to 12.7 % RSD,
      respectively. The detection limit of the analytical method was 3.5 ng/g. The
      ability for gliotoxin production by A. fumigatus revealed that 61.5 % of the
      strains were able to produce the toxin at levels ranging from LOQ to 3430.5 ng/g.
      However, all the tested samples had similar percentages of producing strains
      (81.8 to 86.6 %). The micro-analytical sample treatment coupled with LC-MS/MS
      detection is a precise and useful methodology for determining gliotoxin from
      fungal extracts of A. fumigatus and allows working both fast and safely and also
      reducing the effect on the environment. This toxin plays a critical role in the
      pathobiology of A. fumigatus, and its presence in animal environments could
      affect animal health and productivity; in addition, there are risks of
      contamination for rural workers during handling and storage of animal feedstuffs.

PMID- 25982451
TI  - Dehydroeffusol effectively inhibits human gastric cancer cell-mediated
      vasculogenic mimicry with low toxicity.
AB  - Accumulated data has shown that various vasculogenic tumor cells, including
      gastric cancer cells, are able to directly form tumor blood vessels via
      vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating
      progression and metastasis of malignant tumors. Therefore, tumor vasculogenic
      mimicry is a rational target for developing novel anticancer therapeutics.
      However, effective antitumor vasculogenic mimicry-targeting drugs are not
      clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl
      phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb
      Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric
      cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low
      toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion,
      migration, and invasion. Molecular mechanistic studies revealed that
      dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master
      gene VE-cadherin and reduced adherent protein exposure on the cell surface by
      inhibiting gene promoter activity. In addition, dehydroeffusol significantly
      decreased the expression of a key vasculogenic gene matrix metalloproteinase 2
      (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together,
      our results showed that dehydroeffusol effectively inhibited gastric cancer cell
      mediated vasculogenic mimicry with very low toxicity, suggesting that
      dehydroeffusol is a potential drug candidate for anti-gastric cancer
      neovascularization and anti-gastric cancer therapy. 

PMID- 25982452
TI  - Anything to Stay Alive: The Challenges of a Campaign for an Experimental Drug.
AB  - Drug-resistant tuberculosis (TB) has a high mortality rate. Most medicines used
      to treat it are poorly tested and have terrible side effects. Activists have
      campaigned for patients with drug-resistant TB to have access to experimental
      drugs, particularly one called bedaquiline, before these have been approved by
      regulatory authorities such as the Food and Drug Administration (FDA) in the
      United States (US) and the Medicines Control Council (MCC) in South Africa. Some
      activists have also campaigned for bedaquiline to be approved by regulatory
      authorities before testing of the drug is completed. These campaigns raise
      ethical concerns about whether patients should be offered experimental,
      unapproved, medicines for the treatment of life-threatening illnesses, and if
      authorities should approve drugs for life-threatening illnesses when vital
      questions about safety and efficacy remain outstanding. 

PMID- 25982453
TI  - Risk factors for colonization with extended-spectrum beta-lactamase producing
      Enterobacteriaceae in healthcare students on clinical assignment abroad: A
      prospective study.
AB  - BACKGROUND: The increase of antibiotic resistance in clinically important
      bacteria is a worldwide threat, especially in healthcare environments.
      International travel is a risk factor for gut colonization with extended-spectrum
      beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk for healthcare
      students of being colonized with ESBL-PE when participating in patient-related
      work abroad has not been previously investigated. METHODS: Swedish healthcare
      students travelling for pre-clinical and clinical courses outside Scandinavia
      submitted faecal samples and survey data before and after travel. The faecal
      samples were screened for ESBL-PE and carbapenemase-producing Enterobacteriaceae
      (CPE). Screening results and survey data were analysed to identify risk factors
      for colonization. RESULTS: In the 99 subjects who submitted a full set of
      samples, 35% were colonized with a new ESBL-PE strain during travel. No CPE was
      found. The most important risk factor for ESBL-PE colonization was travel
      destination, and the highest colonization rate was found in the South-East Asia
      region. Antibiotic treatment during travel was an independent risk factor for
      ESBL-PE colonization but patient-related work was not significantly associated
      with an increased risk. CONCLUSIONS: Patient-related work abroad was not a risk
      factor for ESBL-PE suggesting that transmission from patients is uncommon. Pre
      travel advice on avoiding unnecessary antibiotic treatment during travel is
      recommended.

PMID- 25982454
TI  - Effectiveness of maxillary protraction using facemask with or without maxillary
      expansion: a systematic review and meta-analysis.
AB  - OBJECTIVES: Class III therapy using a face mask is a common approach for
      treatment of a deficient maxilla and reverse overbite. Usually, maxillary
      protraction is combined with transverse palatal expansion using intraoral
      appliances. The purpose of this study was to systematically review the
      effectiveness of face mask therapy in combination with concepts of palatal
      expansion and compression. MATERIAL AND METHODS: A systematic review and meta
      analysis were performed to identify studies that address class III treatment
      using a face mask. The search was carried out using common electronic databases
      as well as hand search. Both screening and study eligibility analysis were
      performed with consideration of PRISMA and Cochrane Guidelines for systematic
      reviews. Several terms describing class III face mask treatment were searched.
      Particular attention was paid to new strategies of enhancing maxillary
      protraction. RESULTS: The initial search identified 2048 studies. After a
      thorough selection process, a total of 22 articles met the inclusion criteria.
      After assessment of the individual quality scoring of each article, eight studies
      were provided for meta-analysis of the cephalometric parameters. The statistical
      analysis of treatment changes advocates a positive influence on sagittal
      maxillary development, which is not primarily influenced by transverse expansion.
      Dental side effects are more distinct when no expansion was carried out. For the
      concept of alternating activation/deactivation of the expansion appliance (alt
      RAMEC), two articles of high methodological scoring were identified. They
      indicate an enhancement of face mask treatment. CONCLUSIONS: The findings are
      consistent with results of previous literature studies regarding the efficiency
      of class III face mask treatment. A further need for more randomized controlled
      studies was identified especially with regard to the new concept of alternating
      maxillary expansion and compression, which showed a positive influence on the
      maxillary protraction based on two studies. CLINICAL RELEVANCE: Class III therapy
      using extraoral face mask anchorage is effective for maxillary protraction. The
      recently discussed new protocols potentially improve this treatment.

PMID- 25982455
TI  - Overexpression of BCL2 and BAX following BFM induction therapy predicts ch-ALL
      patients' poor response to treatment and short-term relapse.
AB  - PURPOSE: The identification of childhood acute lymphoblastic leukemia (ch-ALL)
      patients who are at a higher risk of chemotherapy resistance and relapse is
      essential for successful treatment decisions, despite the application of novel
      therapies. The aim of the study is the evaluation of BCL2 and BAX expression for
      the prognosis of ch-ALL patients treated with Berlin-Frankfurt-Munster (BFM)
      backbone protocol. METHODS: Bone marrow specimens were obtained at the time of
      diagnosis and on day 33 following BFM treatment induction from 82 ch-ALL
      patients, as well as from 63 healthy children. Following extraction, total RNA
      was reverse transcribed and BCL2 and BAX expression levels were determined by
      qPCR. RESULTS: BCL2 expression and BCL2/BAX ratio were strongly upregulated in ch
      ALL compared to healthy children and were correlated with favorable prognostic
      disease features. Increased levels of BCL2 and BAX expression were associated
      with disease remission, as ch-ALL patients with lower expression ran a
      significantly higher risk of M2-M3 response, positive MRD and poor survival
      outcome. Moreover, the upregulation of BCL2 and BAX following BFM treatment
      induction was shown to represent an independent predictor of patients' short-term
      relapse, which was further confirmed in ch-ALL patients with favorable prognostic
      markers. CONCLUSIONS: In conclusion, BCL2 and BAX could be effectively used for
      an enhanced prediction of BFM-treated patients' outcome.

PMID- 25982456
TI  - Long-term outcome in children with infantile spasms treated with vigabatrin: A
      cohort of 180 patients.

PMID- 25982457
TI  - Invitation to participate in the EpiNet-First trials.

PMID- 25982458
TI  - In response to: Long-term outcome in children with infantile spasms treated with
      vigabatrin: A cohort of 180 patients.

PMID- 25982459
TI  - Unexpected furanose/pyranose equilibration of N-glycosyl sulfonamides, sulfamides
      and sulfamates.
AB  - De-protected arabino N-glycosyl sulfamides, sulfonamides and sulfamates were
      found to mutarotate and convert from the furanose to the thermodynamically more
      stable pyranose form in aqueous solution. The presence of a strongly electron
      withdrawing group in the alkyl chain stopped mutarotation and furanose/pyranose
      equilibration, allowing the isolation of the first unprotected furanose N
      glycosyl sulfonamide. 

PMID- 25982460
TI  - Erratum: Genomes and phenomes of a population of outbred rats and its
      progenitors.
AB  - [This corrects the article DOI: 10.1038/sdata.2014.11.]. 

PMID- 25982461
TI  - Preliminary discussion on the value of (18)F-FDG PET/CT in the diagnosis and
      early staging of non-mycosis fungoides/Sezary's syndrome cutaneous malignant
      lymphomas.
AB  - OBJECTIVE: To discuss the value of (18)F-fluorodeoxyglucose-positron emission
      tomography ((18)F-PET/CT) scans in the diagnosis and early staging of non-mycosis
      fungoides/Sezary's syndrome cutaneous malignant lymphomas (non-MF/SS CML).
      MATERIALS AND METHODS: A total of 18 cases with non-MF/SS CML, confirmed by
      pathology or on clinical grounds, were analyzed in this study. The sensitivity of
      CT and PET/CT scans in the diagnosis of primary skin lesions, as well as the
      sensitivity, specificity, accuracy, positive predictive value, and negative
      predictive value of CT and PET/CT scans in the diagnosis of lymph nodes (LNs) and
      other organs (except skin and LNs) were calculated. RESULTS: The diagnostic
      sensitivity of CT and PET/CT scans in the diagnosis of primary skin lesions was
      82.4% (14/17) and 100% (17/17), respectively. The diagnostic sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of CT and PET/CT scans in the diagnosis of LN lesions were 55.6% (5/9), 88.9%
      (8/9), 72.2% (13/18), 83.3% (5/6), 66.7% (8/12), and 88.9% (8/9), 100% (9/9),
      94.4% (17/18), 100% (8/8), 90.0% (9/10), respectively. The diagnostic value of
      the CT and PET/CT scans in the diagnosis of involvement of other organs, were
      40.4% (2/5), 100% (13/13), 83.3 (15/18), 100% (2/2), 81.3% (13/16) and 80.6%
      (4/5), 100% (13/13), 94.4% (17/18), 100% (3/3), 92.9% (13/14), respectively.
      CONCLUSIONS: (18)F-FDG PET/CT has high value in the diagnosis and early staging
      of non-MF/SS CMLs.

PMID- 25982462
TI  - Dietary fatty acid intakes are related to the risk of ulcerative colitis: a case
      control study.
AB  - INTRODUCTION: The role of dietary fatty acids in ulcerative colitis (UC)
      pathogenesis has been shown in animal models; however, human studies are rare. We
      hypothesized that there might be a relationship between dietary fatty acid
      composition and the risk of developing incident UC. MATERIAL AND METHODS:
      Overall, 62 new cases of UC and 124 healthy age and sex-matched controls were
      studied. Information on usual diet was measured by a validated country-specific
      food frequency questionnaire (FFQ). Logistic regression analysis adjusting for
      potential confounding variables was carried out to compare dietary fatty acid
      intakes between cases and controls. RESULTS: We found positive associations
      between dietary intake of total fat (P value for trend <0.01), oleic acid (P
      value for trend <0.01), saturated fatty acid (SAFA) (P value for trend = 0.02),
      total polyunsaturated fatty acid (PUFA) (P value for trend = 0.04), and trans fat
      (P value for trend <0.01). CONCLUSION: Our results showed that higher
      consumptions of total fats, oleic acid, SAFAs, total PUFAs, trans fat, MUFAs, and
      linoleic acid are significantly associated with increased risk for UC; however,
      no statistically significant associations were detected between the risk of
      disease and n-3 PUFAs and cholesterol intake.

PMID- 25982463
TI  - Unusual presentation of endometrioid adenocarcinoma arising in colonic
      endometriosis. A case report.

PMID- 25982465
TI  - Vulvar inflammation as the presenting sign of Crohn's disease.

PMID- 25982464
TI  - Short-term clinical outcomes of robot-assisted intersphincteric resection and low
      rectal resection with double-stapling technique for cancer: a case-matched study.

PMID- 25982466
TI  - Intestinal spirochetosis: an unusual cause of IBD flare-up during anti-TNF
      therapy.

PMID- 25982467
TI  - Recurrent volvular herniation of the ileal pouch: a case report and literature
      review.

PMID- 25982468
TI  - Role of intraoperative frozen section for assessing distal resection margin after
      anterior resection.
AB  - BACKGROUND AND AIMS: The use of neoadjuvant long-course chemoradiotherapy (LCRT),
      shorter distal safety margins (DSMs) and stapled or intersphincteric resections
      has increased sphincter preservation rates. While intraoperative frozen section
      (IOFS) is not mandatory, it helps achieve negative distal resection margins
      (DRMs). Our aim was to audit the role of IOFS for DRM assessment while performing
      sphincter-saving rectal surgery and to identify those subgroups that would
      benefit the most from IOFS analysis. METHODS: Patients who underwent rectal
      cancer surgery between 2009 and 2013 were identified from a prospectively
      maintained database. Patients who intraoperatively underwent an IOFS for DRM
      assessment were included in the study. Factors associated with a positive margin
      on IOFS were analysed. The sensitivity and specificity of IOFS were also
      assessed. RESULTS: Of 250 patients, who had an anterior resection with an IOFS,
      12 had an involved DRM. Of these patients, eight were involved by adenocarcinoma,
      two by acellular mucin, one by moderate dysplasia and one by adenoma confirmed on
      paraffin section. Positive margins had a 100 % intervention rate. There were two
      false negative on IOFS. IOFS had a sensitivity of 85.17 % with a specificity of
      100 % and a negative predictive value of 99.16 %. Specimens with a positive IOFS
      were lower rectal (P < 0.05), poorly differentiated and post LCRT locally
      advanced tumours. CONCLUSIONS: IOFS to confirm negative DRM is recommended in
      lower rectal tumours irrespective of DSM. It can be considered for locally
      advanced post LCRT poorly differentiated mid rectal tumours and avoided for upper
      rectal tumours.

PMID- 25982469
TI  - A single bout of whole-leg, peristaltic pulse external pneumatic compression
      upregulates PGC-1alpha mRNA and endothelial nitric oxide sythase protein in human
      skeletal muscle tissue.
AB  - NEW FINDINGS: What is the central question of this study? Does 60 min of
      peristaltic pulse external pneumatic compression (EPC) alter gene and protein
      expression patterns related to metabolism, vascular biology, redox balance and
      inflammation in vastus lateralis biopsy samples? What is the main finding and its
      importance? A single bout of EPC transiently upregulates PGC-1alpha mRNA, while
      also upregulating endothelial nitric oxide synthase protein and nitric oxide
      metabolite concentrations in vastus lateralis biopsy samples. We investigated
      whether a single 60 min bout of whole-leg, lower pressure external pneumatic
      compression (EPC) altered select vascular, metabolic, antioxidant and
      inflammation-related mRNAs. Ten participants (eight male, two female; aged 22.0
      +/- 0.4 years) reported to the laboratory 4 h postprandial, and vastus lateralis
      muscle biopsies were obtained before (PRE) and 1 and 4 h after EPC treatment.
      Messenger RNA expression was analysed using real-time RT-PCR, and significant
      mRNA findings were investigated further by Western blot analysis of respective
      protein concentrations. Peroxisome proliferator-activated receptor gamma
      coactivator-1alpha (PGC-1alpha) mRNA increased by 77% 1 h following EPC compared
      with PRE levels (P = 0.005), but no change in protein concentration 1 or 4 h post
      EPC was observed. Increases in endothelial nitric oxide sythase (eNOS) mRNA
      (+44%) and superoxide dismutase 2 (SOD2) mRNA (+57%) 1 h post-EPC as well as an
      increase in interleukin-10 mRNA (+132%) 4 h post-EPC compared with PRE levels
      were observed, but only approached significance (P = 0.076, 0.077 and 0.074,
      respectively). Interestingly, eNOS protein (+40%, P = 0.025) and nitrate and
      nitrite (NOx) concentrations (+69%, P = 0.025) increased 1-4 h post-EPC.
      Moreover, SOD2 protein tended to increase from PRE to 4 h post-EPC (+43%, P =
      0.074), although no changes in tissue 4-hydroxnonenal levels was observed. An
      acute bout of EPC transiently upregulates PGC-1alpha mRNA, while also
      upregulating eNOS protein and NOx concentrations in vastus lateralis biopsy
      samples. Future research should characterize the origin of these responses (e.g.
      vascular or muscle fibre cells) and how the acute effects of EPC application on
      gene and protein expression observed herein are associated with functional
      improvements (e.g. metabolism, vascular function) in acute and chronic models.

PMID- 25982471
TI  - Validating a human biotelemetry system for use in captive blue wildebeest
      (Connochaetes taurinus).
AB  - We fitted two blue wildebeest (Connochaetes taurinus) with modified versions of
      the EquivitalTM EQ02 wireless monitoring system to evaluate if the device could
      accurately measure heart rate and respiration rate in this species whilst
      anaesthetized as well as whilst fully conscious in captivity. Whilst under
      anaesthesia, we monitored each animal's heart rate and respiration rate using the
      EquivitalTM biotelemetry belt, a Cardell((r)) veterinary monitor and manual
      measurements. The animals were also administered doxapram hydrochloride
      (Dopram((r)) ) and adrenaline intravenously at different times to stimulate
      changes in respiration and heart rate, respectively. Once 30 minutes of
      monitoring was completed, we reversed the anaesthetic and left the animals in
      captivity for 24 hours whilst wearing the EquivitalTM belts. After 24 hr, we
      repeated the anaesthesia and monitoring as well as the administration of the
      doxapram hydrochloride and adrenaline. Intraclass Correlation Coefficients (ICC)
      calculated between all three monitoring methods showed moderate to excellent
      agreements for heart rate on both days (ICC: 0.73-0.98). ICCs calculated between
      the three methods for respiration rate showed good to excellent agreement between
      the Equivital belt and the other two methods (0.82-0.92) with the exception of
      occasions when only poor to fair agreements were found between the Cardell((r))
      measurements and manual measurements. Heart rate and respiration rate were also
      found to increase with motion while animals were in captivity. The results
      indicate that a modified version of the EquivitalTM EQ02 system can be used as a
      potential biotelemetry device for measuring heart and respiration rate in captive
      blue wildebeest.

PMID- 25982472
TI  - [Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates
      in relation to placental impairment severity].
AB  - INTRODUCTION: Intrauterine growth restriction (IUGR) and prematurity have been
      associated with increased perinatal morbidity and mortality and also with
      cardiovascular foetal programming. However, there are few studies on the impact
      of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in
      pre-term infants. OBJECTIVES: To determine differences in neonatal morbidity,
      mortality and cord blood biomarkers of cardiovascular dysfunction between pre
      term placenta-related IUGR and non-IUGR new-borns, and to analyse their
      relationship with the severity of IUGR according to foetal Doppler evaluation.
      MATERIAL AND METHODS: Prospective cohort study: pre-term infants with placenta
      related IUGR and matched pre-term infants without IUGR. A Doppler scan was
      performed, and placenta-IUGR was classified according to severity. Comparative
      analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood
      levels of biomarkers of cardiovascular dysfunction was performed. RESULTS: IUGR
      new-borns present lower weight, length, head circumference, and Apgar score at
      birth, as well as increased neonatal and cardiovascular dysfunction biomarker
      levels, compared with pre-term new-borns without IUGR. These differences increase
      with the severity of IUGR determined by prenatal umbilical artery Doppler scan.
      CONCLUSIONS: Placenta-related-IUGR pre-term infants, irrespective of gestational
      age, present increased neonatal morbidity and mortality that is significantly
      proportional to the severity of IUGR. Placental impairment and severity also
      determine levels of cardiovascular dysfunction biomarkers at birth.

PMID- 25982473
TI  - [A consequence of alcohol abuse].

PMID- 25982474
TI  - [Ultrasound of the urinary system].
AB  - Ultrasound techniques are able to provide a fairly complete examination of the
      urinary system, achieving a high sensitivity in relevant-pathology detection,
      especially in the kidney, bladder and prostate. Early detection of pathologies
      such as tumors or urinary tract obstructions, sometimes even before their
      clinical manifestation, has improved their management and prognosis in many
      cases. This, added to its low cost and harmlessness, makes ultrasound ideal for
      early approaches and follow-up of a wide number of urinary system pathologies. In
      this article, the ultrasound characteristics of the main urinary system
      pathologies that can be diagnosed by this technique, are reviewed. 

PMID- 25982475
TI  - [RS3PE syndrome: An update on its treatment using the presentation of a case].
AB  - The present study was undertaken in order to try to clarify certain aspects of
      RS3PE syndrome, for which there is no unanimity of opinion in the current
      literature. An attempt will be made to clarify the best and most suitable drug
      for treatment, and the dosage duration. In order to do this, a literature search
      was performed, and a review is presented of the 108 cases collected. In 95% cases
      glucocorticoids were the most used, with prednisone in being used in 68.5% of
      cases. Although there is no unanimity criteria regarding the dosage and duration,
      73.8% cases were treated with a prednisone dose from 15 to 20 mg/day (median 18.2
      mg/day, SD 8.9). Two-thirds (66.1%) of cases were treated for 3 to 6 months
      (median 5.3 months, SD 3.8). A case is presented that serves as a common thread
      of these observations.

PMID- 25982476
TI  - Alternative technique for nipple-areola complex reconstruction with poor skin
      condition.
AB  - BACKGROUND: Reconstruction of the nipple-areola complex (NAC) is generally the
      final step in breast reconstruction. NAC reconstructions are frequently
      complicated by scars, which are a common complication of radical surgery.
      Sometimes, radiotherapy further complicates these cases. METHODS: Under these
      conditions, we present an alternative technique with a better chance of ensuring
      the vitality of the reconstructed NAC. We evaluated in a 35-patient group (G1)
      the average healing time, the subjective perception (aesthetics satisfaction),
      projection and diameter of the NAC as measures of the aesthetic and safety of the
      results compared with those of a control group 2 who underwent traditional
      techniques reconstruction. RESULTS: We present the following results: an average
      post-op projection of 5 +/- 2 mm in group 1 and 8 +/- 2 mm in group 2; good
      stability over a 12-month period: lower reduction of the NAC projection
      (cumulative values within 2 mm) has been 80% in group 1 and 68.57% in the control
      group G2. A faster full recovery has been observed without post-operative
      complications in group 1 (11 +/- 2 days) versus group 2 (14 +/- 2 days) with
      minor complications. Other parameters were good in measures and comparable in
      both groups. CONCLUSION: According to our data, this technique appears to ensure
      a good aesthetic result with acceptable stability over time. Moreover, healing
      process appears to be faster and less complicated in the experimental group.

PMID- 25982477
TI  - Down-regulation of 14-3-3beta exerts anti-cancer effects through inducing ER
      stress in human glioma U87 cells: Involvement of CHOP-Wnt pathway.
AB  - We previously identified 14-3-3beta as a tumor-specific isoform of 14-3-3 protein
      in astrocytoma, but its functional role in glioma cells and underlying mechanisms
      are poorly understood. In the present study, we investigated the effects of 14-3
      3beta inhibition in human glioma U87 cells using specific targeted small
      interfering RNA (siRNA). The results showed that 14-3-3beta is highly expressed
      in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3beta by
      Si-14-3-3beta transfection significantly decreased the cell viability but
      increased the LDH release in a time-dependent fashion in U87 cells, and these
      effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition,
      14-3-3beta knockdown induced ER stress in U87 cells, as evidenced by ER calcium
      release, increased expression of XBP1S mRNA and induction of ER related pro
      apoptotic factors. Down-regulation of 14-3-3beta significantly decreased the
      nuclear localization of beta-catenin and inhibited Topflash activity, which was
      shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were
      used to inhibit CHOP and Wnt, respectively. The results showed that the anti
      cancer effects of 14-3-3beta knockdown in U87 cells were mediated by increased
      expression of CHOP and followed inhibition of Wnt/beta-catenin pathway. In
      summary, the remarkable efficiency of 14-3-3beta knockdown to induce apoptotic
      cell death in U87 cells may find therapeutic application for the treatment of
      glioma patients. 

PMID- 25982478
TI  - A novel splice variant of human L-selectin encodes a soluble molecule that is
      elevated in serum of patients with rheumatic diseases.
AB  - L-selectin, a type I membrane protein, is a leukocyte adhesion molecule that
      mediates both lymphocyte homing to peripheral lymph nodes and leukocyte
      accumulation at sites of inflammation. L-selectin is rapidly shed from the cell
      surface after cellular activation, and the ectodomain thus released is thought to
      account for high levels of soluble L-selectin in serum. In this study, we report
      the identification of a novel, naturally occurring isoform of the human L
      selectin gene. Sequence analysis revealed that this isoform is generated by an
      alternative splicing event: the 7th exon of the human L-selectin gene, which
      encodes the region containing the transmembrane domain, is excluded, predicting a
      soluble protein product. The mRNA for this splice variant was expressed in
      lymphoid organs, where conventional L-selectin mRNA was also expressed.
      Activating T cells increased the variant mRNA and its ratio to the membrane form.
      Soluble L-selectin translated from the variant mRNA was present in human serum,
      albeit at a much lower level than that arising from ectodomain shedding, and was
      markedly elevated in patients with various rheumatic diseases, including
      rheumatoid arthritis and systemic lupus erythematosus. These observations
      indicate that some of the soluble L-selectin present in human serum arises
      through alternative splicing, which may be upregulated during lymphocyte
      activation in patients with various clinical conditions. 

PMID- 25982480
TI  - Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens-Johnson
      syndrome and toxic epidermal necrolysis.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and
      life-threatening cutaneous adverse drug reactions. While there is no established
      therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v.
      immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still
      controversial because total doses of IVIG used vary greatly from one study to
      another. The aim of this study was to evaluate the efficacy of IVIG,
      administrated for 5 days consecutively, in an open-label, multicenter, single-arm
      study in patients with SJS or TEN. IVIG (400 mg/kg per day) administrated for 5
      days consecutively was performed as an additional therapy to systemic steroids in
      adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated.
      Parameters to assess clinical outcome were enanthema including ophthalmic and
      oral lesions, cutaneous lesions and general condition. These parameters were
      scored and recorded before and after IVIG. We enrolled five patients with SJS and
      three patients with TEN who did not respond sufficiently to systemic steroids
      before IVIG administration. All of the patients survived and the efficacy on day
      7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin
      lesions and enanthema in the patients in whom IVIG therapy was effective. Serious
      side-effects from the use of IVIG were not observed. IVIG (400 mg/kg per day)
      administrated for 5 days consecutively seems to be effective in patients with SJS
      or TEN. IVIG administrated together with steroids should be considered as a
      treatment modality for patients with refractory SJS/TEN. Further studies are
      needed to define the therapeutic efficacy of IVIG. 

PMID- 25982479
TI  - The 'Early Developmental Stages of Psychopathology (EDSP) study': a 20-year
      review of methods and findings.
AB  - PURPOSE: The "Early Developmental Stages of Psychopathology (EDSP)" study is a
      prospective-longitudinal study program in a community sample (Munich, Germany) of
      adolescents and young adults. The program was launched in 1994 to study the
      prevalence and incidence of psychopathological syndromes and mental disorders, to
      describe the natural course and to identify vulnerability and risk factors for
      onset and progression as well as psychosocial consequences. This paper reviews
      methods and core outcomes of this study program. METHODS: The EDSP is based on an
      age-stratified random community sample of originally N = 3021 subjects aged 14-24
      years at baseline, followed up over 10 years with up to 3 follow-up waves. The
      program includes a family genetic supplement and nested cohorts with lab
      assessments including blood samples for genetic analyses. Psychopathology was
      assessed with the DSM-IV/M-CIDI; embedded dimensional scales and instruments
      assessed vulnerability and risk factors. RESULTS: Beyond the provision of age
      specific prevalence and incidence rates for a wide range of mental disorders,
      analyses of their patterns of onset, course and interrelationships, the program
      identified common and diagnosis-specific distal and proximal vulnerability and
      risk factors including critical interactions. CONCLUSIONS: The EDSP study
      advanced our knowledge on the developmental pathways and trajectories, symptom
      progression and unfolding of disorder comorbidity, highlighting the dynamic
      nature of many disorders and their determinants. The results have been
      instrumental for defining more appropriate diagnostic thresholds, led to the
      derivation of symptom progression models and were helpful to identify promising
      targets for prevention and intervention.

PMID- 25982483
TI  - Bone health and nutrition: Introduction to the special issue.

PMID- 25982481
TI  - Single-dose local simvastatin injection improves implant fixation via increased
      angiogenesis and bone formation in an ovariectomized rat model.
AB  - BACKGROUND: Statins have been reported to promote bone formation. However, taken
      orally, their bioavailability is low to the bones. Implant therapies require a
      local repair response, topical application of osteoinductive agents, or
      biomaterials that promote implant fixation. MATERIAL/METHODS: The present study
      evaluated the effect of a single local injection of simvastatin on screw fixation
      in an ovariectomized rat model of osteoporosis. RESULTS: Dual-energy X-ray
      absorptiometry, micro-computed tomography, histology, and biomechanical tests
      revealed that 5 and 10 mg simvastatin significantly improved bone mineral density
      by 18.2% and 22.4%, respectively (P<0.05); increased bone volume fraction by
      51.0% and 57.9%, trabecular thickness by 16.4% and 18.9%, trabeculae number by
      112.0% and 107.1%, and percentage of osseointegration by 115.7% and 126.3%; and
      decreased trabeculae separation by 34.1% and 36.6%, respectively (all P<0.01).
      Bone mineral apposition rate was significantly increased (P<0.01). Furthermore,
      implant fixation was significantly increased (P<0.05), and bone morphogenetic
      protein 2 (BMP2) expression was markedly increased. Local injection of a single
      dose of simvastatin also promoted angiogenesis. Vessel number, volume, thickness,
      surface area, and vascular volume per tissue volume were significantly increased
      (all P<0.01). Vascular endothelial growth factor (VEGF), VEGF receptor-2, von
      Willebrand factor, and platelet endothelial cell adhesion molecule-1 expression
      were enhanced. CONCLUSIONS: A single local injection of simvastatin significantly
      increased bone formation, promoted osseointegration, and enhanced implant
      fixation in ovariectomized rats. The underlying mechanism appears to involve
      enhanced BMP2 expression and angiogenesis in the target bone.

PMID- 25982482
TI  - Acute and subchronic toxicity of 20  kHz and 60  kHz magnetic fields in rats.
AB  - Despite increasing use of intermediate frequency (IF) magnetic fields (MFs) in
      occupational and domestic settings, scientific evidence necessary for health risk
      assessments of IF MF is insufficient. Male and female Crl:CD(SD) rats (12 per sex
      per group) were exposed to 20 kHz, 0.20 mT(root mean square, rms) or 60 kHz, 0.10
      mT(rms) sinusoidal MFs for 22 h day(-1) for 14 days (acute) or 13 weeks
      (subchronic). Experiments were duplicated for each frequency to ensure outcome
      reproducibility, and examinations were blinded for quality assurance. All rats
      survived without significant clinical signs until the end of experiments. Some
      changes in body weight between the MF-exposed and control groups were observed
      over the course of exposure, although the directions of the changes were
      inconsistent and not statistically significant after subchronic exposure. There
      were significant differences between MF-exposed and control groups in some organ
      weights and parameters in hematology and clinical chemistry, but these were minor
      in magnitude and not repeated in duplicate experiments. Histopathological
      findings reflecting toxicity were sporadic. Frequencies of other findings were
      similar to historic data in this rat strain, and findings had no specific
      relationship to changes in organ weight or parameters of hematology and clinical
      chemistry in each animal. The changes observed throughout this study were
      considered biologically isolated and were attributable to chance associations
      rather than to MF exposure. The results, in particular the histopathological
      evidence, indicate an absence of toxicity in IF MF-exposed rats and do not
      support the hypothesis that IF MF exposure produces significant toxicity.

PMID- 25982484
TI  - Chronic myelomonocytic leukaemia associated with acquired haemophilia A: case
      report and literature review.

PMID- 25982485
TI  - The influence of tumour blood perfusion variability on thermal damage during
      nanoparticle-assisted thermal therapy.
AB  - PURPOSE: This study investigates the influence of blood perfusion variability
      within a tumour and the surrounding healthy tissue during nanoparticle-assisted
      thermal therapy. It seeks to define ideal therapeutic parameters for a wide range
      of perfusion rates to attain the desired thermal damage. MATERIAL AND METHODS:
      Pennes' bioheat model and the Arrhenius model are used to evaluate the thermal
      damage for a two-dimensional tumour surrounded by healthy tissue. A wide range of
      tumour perfusion rates were modelled, ranging from moderate to high perfusion in
      both a homogenously and a heterogeneously perfused tumour. RESULTS: For low
      perfusion rates, a temporal variation in blood perfusion does not critically
      influence the thermal damage. For moderately and highly perfused tumours,
      temporal variation in blood perfusion extends the thermal damage zone by 25-52%
      compared to a constant perfusion rate. For the tumour size and perfusion
      conditions under consideration, the ideal therapeutic parameters were found to be
      irradiation intensity of 1 W/cm(2), and irradiation duration of 105-150 s, for a
      nanoparticle volume fraction of 0.001%. CONCLUSIONS: It is concluded for low
      perfusion rates that due to shorter therapeutic duration, nanoparticle-assisted
      thermal therapy is relatively insensitive to changes in the perfusion rate during
      the therapy. For moderately and highly perfused tumours, a constant perfusion
      under-predicts the real thermal damage zone. This study concludes that for
      moderately and highly perfused tumours the spatial as well as temporal blood
      perfusion dynamics should be carefully accounted for to get a realistic estimate
      of thermal damage zone.

PMID- 25982486
TI  - Very late bioresorbable vascular scaffold thrombosis: a new clinical entity.

PMID- 25982487
TI  - Severe intraventricular dynamic gradient following transcatheter aortic valve
      implantation: suicide ventricle?

PMID- 25982489
TI  - Estimating emissions from adhesives and sealants uses and manufacturing for
      environmental risk assessments.
AB  - Regulation (EC) No 1907/2006 concerning the Registration, Evaluation,
      Authorisation and Restriction of Chemicals (REACH) requires that environmental
      exposure assessments be performed for all uses of dangerous substances that are
      marketed in the European Union in quantities above 10 tons per year. The
      quantification of emissions to the environment is a key step in this process.
      This publication describes the derivation of release factors and gives guidance
      for estimating use rates for quantifying the emissions from the manufacturing and
      application of adhesives and sealants. Release factors available for coatings and
      paints are read across to adhesives or sealants based on similarities between
      these 2 product groups with regard to chemical composition and to processing
      during manufacturing and application. The granular emission scenarios in these
      documents are mapped to the broad emission scenarios for adhesives or sealants.
      According to the mapping, the worst-case release factors for coatings or paints
      are identified and assigned to the adhesives or sealants scenarios. The resulting
      10 specific environmental release categories (SPERCs) for adhesives and sealants
      are defined by differentiating between solvent and nonsolvent ingredients and
      between water-borne and solvent-borne or solvent-free products. These cover the
      vast majority of the production processes and uses and are more realistic than
      the 5 relevant emission estimation defaults provided in the REACH guidance. They
      are accompanied with adhesive or sealant consumption rates in the EU and with
      guidance for estimating conservative substance use rates at a generic level. The
      approach of combining conservative SPERC release factors with conservative
      estimates of substance rates is likely to yield emission estimates that tend to
      overpredict actual releases. Because this qualifies the approach for use in lower
      tier environmental exposure assessment, the Association of the European Adhesive
      & Sealant Industry (FEICA) SPERCs are available in several exposure assessment
      tools that are used under REACH. Given the limited regional variation in the
      manufacturing and use processes of adhesives and sealants, the SPERCs may be
      applicable for emission estimation not only in the EU but also in other regions.

PMID- 25982488
TI  - Affective context interferes with brain responses during cognitive processing in
      borderline personality disorder: fMRI evidence.
AB  - Emotion dysregulation in borderline personality disorder (BPD) is associated with
      loss of cognitive control in the face of intense negative emotion. Negative
      emotional context may interfere with cognitive processing through the
      dysmodulation of brain regions involved in regulation of emotion, impulse
      control, executive function and memory. Structural and metabolic brain
      abnormalities have been reported in these regions in BPD. Using novel fMRI
      protocols, we investigated the neural basis of negative affective interference
      with cognitive processing targeting these regions. Attention-driven Go No-Go and
      X-CPT (continuous performance test) protocols, using positive, negative and
      neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior
      cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task,
      using images from the International Affective Pictures System, targeted the
      hippocampus (HIP). Participants comprised 23 women with BPD, who were compared
      with 15 healthy controls. When Negative>Positive faces were compared in the Go No
      Go task, BPD subjects had hyper-activation relative to controls in areas
      reflecting task-relevant processing: the superior parietal/precuneus and the
      basal ganglia. Decreased activation was also noted in the OFC, and increased
      activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper
      activation in task-relevant areas: the superior parietal/precuneus and the ACC.
      In the stimulus-driven Episodic Memory task, BPD subjects had decreased
      activation relative to controls in the HIP, ACC, superior parietal/precuneus, and
      dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for
      retrieval of Negative>Positive pictures, reflecting impairment of task-relevant
      functions. Negative affective interference with cognitive processing in BPD
      differs from that in healthy controls and is associated with functional
      abnormalities in brain networks reported to have structural or metabolic
      abnormalities. Task demands exert a differential effect on the cognitive response
      to negative emotion in BPD compared with control subjects.

PMID- 25982491
TI  - Dynamic model of nonmedical opioid use trajectories and potential policy
      interventions.
AB  - BACKGROUND: Nonmedical use of pharmaceutical opioid analgesics (POA) increased
      dramatically over the past two decades and remains a major health problem in the
      United States, contributing to over 16 000 accidental poisoning deaths in 2010.
      OBJECTIVES: To create a systems-oriented theory/model to explain the historical
      behaviors of interest, including the various populations of nonmedical opioid
      users and accidental overdose mortality within those populations. To use the
      model to explore policy interventions including tamper-resistant drug
      formulations and strategies for reducing diversion of opioid medicines. METHODS:
      A system dynamics model was constructed to represent the population of people who
      initiate nonmedical POA usage. The model incorporates use trajectories including
      development of use disorders, transitions from reliance on informal sharing to
      paying for drugs, transition from oral administration to tampering to facilitate
      non-oral routes of administration, and transition to heroin use by some users, as
      well as movement into and out of the population through quitting and mortality.
      Empirical support was drawn from national surveys (NSDUH, TEDS, MTF, and ARCOS)
      and published studies. RESULTS: The model was able to replicate the patterns seen
      in the historical data for each user population, and the associated overdose
      deaths. Policy analysis showed that both tamper-resistant formulations and
      interventions to reduce informal sharing could significantly reduce nonmedical
      user populations and overdose deaths in the long term, but the modeled effect
      sizes require additional empirical support. CONCLUSION: Creating a theory/model
      that can explain system behaviors at a systems level scale is feasible and
      facilitates thorough evaluation of policy interventions.

PMID- 25982492
TI  - An Elephant in the Consultation Room?: Configuring Down Syndrome in British
      Antenatal Care.
AB  - This article is based on an ethnographic study of prenatal screening for Down
      syndrome in two British health care institutions. Drawing on observations of
      everyday hospital life and interviews with health care professionals, I identify
      how a discussion of Down syndrome is avoided during prenatal screening
      consultations. This relative silence is created and upheld because of three
      things: (1) the British public is considered as knowing what Down syndrome is;
      (2) the organization of care dictates that the condition is not classified as
      important enough to justify an explanation within consultations; and (3)
      professionals frequently admit to having minimal knowledge of Down syndrome. This
      absence, together with the condition being categorized as a risk or problem,
      helps produce and uphold its status as a negative pregnancy outcome. I conclude
      by highlighting the contributions that this article has for anthropologically
      exploring how ideas around disability intersect with the proliferation of
      reproductive technologies.

PMID- 25982493
TI  - Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X
      Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism.
AB  - Farnesoid X receptor (FXR) plays an important role in the regulation of
      cholesterol, lipid, and glucose metabolism. Recently, several studies on the
      molecular basis of FXR antagonism have been reported. However, none of these
      studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our
      previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a
      novel nonsteroidal FXR ligand was designed and used as a lead for structural
      modification. In total, 39 new trisubstituted isoxazole derivatives were designed
      and synthesized, which led to pharmacological profiles ranging from agonist to
      antagonist toward FXR. Notably, compound 5s (4'-[(3-{[3-(2-chlorophenyl)-5-(2
      thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic
      acid), containing a thienyl-substituted isoxazole ring, displayed the best
      antagonistic activity against FXR with good cellular potency (IC50 =12.2 +/- 0.2
      MUM). Eventually, this compound was used as a probe in a molecular dynamics
      simulation assay. Our results allowed us to propose an essential molecular basis
      for FXR antagonism, which is consistent with a previously reported antagonistic
      mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be
      important for the future design of nonsteroidal antagonists of FXR.

PMID- 25982494
TI  - Effectiveness of a low contrast load CT angiography protocol in octogenarians and
      nonagenarians being evaluated for transcatheter aortic valve replacement.
AB  - INTRODUCTION: Transcatheter aortic valve replacement (TAVR) typically requires
      computed tomographic angiography (CTA) for aortoiliofemoral assessment to
      determine feasibility of a transfemoral approach, although many candidates being
      considered for TAVR are at increased risk of contrast-induced nephropathy (CIN).
      OBJECTIVE: To determine the feasibility and safety of a load contrast load CTA
      protocol in octogenarians and nonagenarians at risk of CIN. APPROACH: We
      evaluated 54 consecutive octogenarians and nonagenarians considered for TAVR who
      underwent CTA using a standard contrast protocol (n=21) versus a protocol
      incorporating low-dose contrast in patients at risk of CIN (n=33). We compared
      clinical characteristics, CTA image quality (score 1-4) and interpretability, and
      clinical outcomes, including CIN and vascular complications. RESULTS: The mean
      age was 88.5+/-4.0 years, 37% were male, and chronic renal insufficiency was
      common in both the standard and low-dose contrast cohorts (57% vs. 70%, P=.39).
      The low-dose contrast protocol was associated with a significantly less contrast
      volume compared to standard contrast protocol (127+/-18 ml vs 76+/-55 ml,
      P<.001). Individuals imaged using low-dose (n=16) versus standard (n=17) contrast
      protocols received 80% less contrast volume (23+/-10 vs. 125+/-23 ml, P<.001).
      There was similar graded image quality (3.8+/-0.4 vs. 3.9+/-0.3, P=.76) and
      interpretability (100% for each, P=1.0) between standard and low-dose contrast
      protocol groups. There was no significant difference in rates of CIN after CTA
      between standard and low-dose contrast protocol groups (10% vs. 3%, P=.55), with
      no CIN events in those imaged by low-dose CTA. There were no major vascular
      injuries associated with TAVR or pigtail insertion, no major bleeding for CTA,
      and no noninterpretable studies in all patients. CONCLUSION: In this proof-of
      principle study, a low-dose contrast protocol appears feasible and safe in
      octogenarians and nonagenarians undergoing screening for TAVR, and results in
      significant reduction in contrast load as compared to a standard contrast
      protocol without observed differences in image quality or safety.

PMID- 25982495
TI  - Vesical varices: an unusual presentation of portal hypertension.
AB  - We present a case of vesical varices manifesting as hematuria in a patient with
      severe portal hypertension. Vesical varices are an uncommon type of ectopic
      varices in patients with portal hypertension and are usually seen in patients who
      have undergone prior interventions that alter portal pressure dynamics. Our case
      demonstrates that this unusual entity was present in a patient without prior
      intervention and serves as reminder to assess for ectopic varices in order to
      mitigate or prevent associated morbidity. 

PMID- 25982496
TI  - Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by
      TNF-alpha and PGE2 and is crucial for liver transplant tolerance.
AB  - The role of mesenchymal stromal cells (MSCs) in the modulation of liver
      transplant tolerance has attracted significant interest. However, the interaction
      between MSCs and Kupffer cells (KCs) has received little attention, and the
      effect of this interaction on liver transplant tolerance remains unclear. KCs
      were cultured in the presence and absence of MSCs. After 24 h, cells were treated
      with lipopolysaccharide (LPS), after which the production of cytokines and the
      expression of surface antigens were measured for cell function identification.
      Moreover, the effects of the KCs and the prostaglandin E2 (PGE2) levels produced
      by the MSCs were determined using an experimental rat liver transplantation
      model. Blood and liver samples were collected at three time points after
      transplantation for further analysis. After LPS treatment, when compared with the
      KC single cultures, the expression of pro-inflammatory cytokines (IL-1beta, IL-6,
      MHC-II, CD40, CD80, and CD86) in the coculture system was down-regulated, whereas
      the expression of anti-inflammatory cytokines (TGF-beta, IL-4, PGE2, and IL-10)
      was markedly increased. These data indicate that MSCs can reprogram the phenotype
      of KCs. However, KCs treated with miR/TNF-alpha (tumor necrosis factor) plasmid
      prior to coculture to inhibit the production of TNF-alpha resulted in an
      inhibition of the reprogramming effect of MSCs. Moreover, overexpression of PGE2
      in MSCs increased the effect of MSCs on KC reprogramming. After rat liver
      transplantation, allograft recipients that received MSCs showed better allograft
      tolerance when compared with rats in which KC function was inhibited.
      Furthermore, rats treated with MSCs overexpressing PGE2 demonstrated the best
      liver tolerance of all of the groups tested. MSCs reprogram the phenotype of KCs
      through TNF-alpha and PGE2, and this process is crucial for the immunomodulatory
      function of MSCs in liver transplantation.

PMID- 25982497
TI  - Incidental diagnosis of an asymptomatic adult-onset Alexander disease by brain
      magnetic resonance imaging for preoperative evaluation.

PMID- 25982498
TI  - Steroid-responsive autoimmune encephalopathy associated with autoimmune
      thyroiditis (SREAT) presenting with myoclonus-dystonia syndrome.

PMID- 25982500
TI  - Altered resting state functional network connectivity in children absence
      epilepsy.
AB  - Altered functional connectivity has been associated with the influence of
      epileptic activity. Abnormalities in connectivity, particularly in dorsal
      attention (DAN), salience (SN) and default mode (DMN) networks, might contribute
      to the loss of consciousness during seizures and cognitive deficits in patients
      with children absence epilepsy (CAE). The objective of the present study was to
      identify whether the functional network connectivity (FNC) is changed between
      patients with CAE and healthy controls. Using independent component analysis,
      twelve resting state networks (RSNs) were identified in resting state functional
      magnetic resonance imaging data sets in eighteen CAE patients and twenty-one
      healthy controls. Analyses of the group differences in FNC strength were
      conducted, controlling for age and gender effects. The findings showed that some
      functional networks were clustered into two subgroups, correlated within
      subgroups and antagonized with each other. Compared with the controls, patients
      with CAE demonstrated abnormal FNC strength among three networks: DMN, DAN and
      SN. In addition, the antagonism of two subgroups was altered. These results might
      reflect the underlying neuronal functional impairment or altered integration
      among these RSNs in CAE, suggesting that the abnormal functional connectivity is
      likely to imply the pathological mechanism associated with the accumulative
      influence of epileptic activity. These findings contribute to the understanding
      of the behavior abnormality in CAE, such as disturbed executive and attentional
      functions and the loss of consciousness during absence seizures. 

PMID- 25982501
TI  - An autopsy case of elderly-onset acute necrotizing encephalopathy secondary to
      influenza.

PMID- 25982499
TI  - The genetic spectrum and the evaluation of CADASIL screening scale in Chinese
      patients with NOTCH3 mutations.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited small artery disease caused by
      NOTCH3 gene mutation. Here we report clinical, pathological and genetic profiles
      of 29 newly-diagnosed CADASIL patients, evaluation of the CADASIL scale in
      Chinese CADASIL patients, and reanalysis of all reported mainland Chinese
      patients with identified NOTCH3 gene mutation. We found two novel mutations
      (p.C134G and p.C291Y) and 13 reported NOTCH3 mutations in the newly-diagnosed
      group. CADASIL scale score was less than the cutoff score in 19 of 53 Chinese
      patients with NOTCH3 mutation, generating only a sensitivity of 64.1%. At the
      time of study, the total number of genetically confirmed CADASIL cases reached
      158 from 97 unrelated mainland Chinese families, with 9/97 (9.3%) sporadic
      patients. The NOTCH3 gene mutation profile showed 43 mutations, with hotspots in
      exon 4, followed by exon 3. The considerable variability in onset age and CADASIL
      scale score in patients carrying the same NOTCH3 missense mutation suggested no
      obvious phenotype-genotype correlation. In conclusion, we report two novel
      mutations which expand the NOTCH3 mutational spectrum. Exons 4 and 3 are hotspots
      in mainland Chinese patients with NOTCH3 mutation. The low sensitivity of CADASIL
      scale in our patients group indicated that the CADASIL scale should be refined
      according to the clinical characteristics of Chinese CADASIL patients when used
      in Chinese populations. 

PMID- 25982502
TI  - Arterial spin-labeling magnetic resonance imaging for diagnosis of early seizure
      after stroke.

PMID- 25982503
TI  - Goodpasture syndrome and posterior reversible encephalopathy syndrome.

PMID- 25982504
TI  - Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model
      of amyotrophic lateral sclerosis.
AB  - BACKGROUND: High-dose of methylcobalamin promotes nerve regeneration in rats with
      acrylamide neuropathy. A double-blind controlled trial suggested that high-dose
      methylcobalamin could increase compound muscle action potentials in patients with
      amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is
      now on-going in ALS (Clinicaltrial.govNCT00444613). We attempted to study whether
      high-dose methylcobalamin can improve symptoms or retard progression of motor
      dysfunction in the wobbler mouse model of ALS. METHODS: After initial diagnosis
      of the disease at the postnatal age of 3-4 weeks, wobbler mice received
      methylcobalamin (3 or 30 mg/kg, n=10/group) or vehicle (n=10), daily for 4 weeks
      by intraperitoneal administration in a blinded fashion. We compared clinical
      symptoms and pathological changes among all groups. Vitamin B12 concentrations
      were measured in the serum, the skeletal muscle and the spinal cord of three
      groups (n=5/group). RESULTS: In comparison with vehicle, mice treated with ultra
      high dose (30 mg/kg) of methylcobalamin significantly inhibited muscle weakness
      and contracture in the forelimb, and increased the weight of the bicep muscles
      and the number of musculocutaneous nerves. Methylcobalamin-treated mice
      significantly elevated vitamin B12 concentrations of the serum, the bicep muscle
      and the spinal cord compared to vehicle. CONCLUSION: Our results suggest that
      treatment with methylcobalamin could delay progression of motor symptoms and
      neuropathological changes in wobbler mouse motor neuron disease if very high
      doses are used.

PMID- 25982505
TI  - EMAS position statement: Non-hormonal management of menopausal vasomotor
      symptoms.
AB  - AIM: To review non-hormonal therapy options for menopausal vasomotor symptoms.
      The current EMAS position paper aims to provide to provide guidance for managing
      peri- and postmenopausal women who cannot or do not wish to take menopausal
      hormone therapy (MHT). MATERIAL AND METHODS: Literature review and consensus of
      expert opinion. RESULTS: Non-hormonal management of menopausal symptoms includes
      lifestyle modifications, diet and food supplements, non-hormonal medications and
      application of behavioral and alternative medicine therapies. There is
      insufficient or conflicting evidence to suggest that exercise, supplements or a
      diet rich in phytoestrogens are effective for vasomotor menopausal symptoms.
      Selective serotonin-reuptake inhibitors (SSRIs), serotonin norepinephrine
      reuptake inhibitors (SNRIs) and gabapentin could be proposed as alternatives to
      MHT for menopausal symptoms, mainly hot flushes. Behavioral therapies and
      alternative medicine interventions have been tried, but the available evidence is
      still limited. CONCLUSIONS: A number of interventions for non-hormonal management
      of menopausal vasomotor symptoms are now available. For women who cannot or do
      not wish to take estrogens, non-hormonal management is now a realistic option.

PMID- 25982506
TI  - Optogenetic control of nerve growth.
AB  - Due to the limited regenerative ability of neural tissue, a diverse set of
      biochemical and biophysical cues for increasing nerve growth has been
      investigated, including neurotrophic factors, topography, and electrical
      stimulation. In this report, we explore optogenetic control of neurite growth as
      a cell-specific alternative to electrical stimulation. By investigating a broad
      range of optical stimulation parameters on dorsal root ganglia (DRGs) expressing
      channelrhodopsin 2 (ChR2), we identified conditions that enhance neurite
      outgrowth by three-fold as compared to unstimulated or wild-type (WT) controls.
      Furthermore, optogenetic stimulation of ChR2 expressing DRGs induces directional
      outgrowth in WT DRGs co-cultured within a 10 mm vicinity of the optically
      sensitive ganglia. This observed enhancement and polarization of neurite growth
      was accompanied by an increased expression of neural growth and brain derived
      neurotrophic factors (NGF, BDNF). This work highlights the potential for
      implementing optogenetics to drive nerve growth in specific cell populations.

PMID- 25982507
TI  - Quantitative characterization of gene regulation by Rho dependent transcription
      termination.
AB  - Rho factor dependent transcription termination (RTT) is common within the coding
      sequences of bacterial genes and it acts to couple transcription and translation
      levels. Despite the importance of RTT for gene regulation, its effects on mRNA
      and protein concentrations have not been quantitatively characterized. Here we
      demonstrate that the exogenous cfp gene encoding the cyan fluorescent protein can
      serve as a model for gene regulation by RTT. This was confirmed by showing that
      Psu and bicyclomycin decrease RTT and increase full length cfp mRNAs (but
      remarkably they have little effect on protein production). We then use cfp to
      characterize the relationship between its protein and full length mRNA
      concentrations when the translation initiation rate is varied by sequence
      modifications of the translation initiation region (TIR). These experiments
      reveal that the fold change in protein concentration (RP) and the fold change in
      full length mRNA concentration (Rm) have the relationship RP~Rm(b), where b is a
      constant. The average value of b was determined from three separate data sets to
      be ~3.6. We demonstrate that the above power law function can predict how
      altering the translation initiation rate of a gene in an operon will affect the
      mRNA concentrations of downstream genes and specify a lower bound for the
      associated changes in protein concentrations. In summary, this study defines a
      simple phenomenological model to help program expression from single genes and
      operons that are regulated by RTT, and to guide molecular models of RTT. 

PMID- 25982508
TI  - Apolipoprotein a1 increases mitochondrial biogenesis through AMP-activated
      protein kinase.
AB  - Apolipoprotein a1, which is a major lipoprotein component of high-density
      lipoprotein (HDL), was reported to decrease plasma glucose in type 2 diabetes.
      Although recent studies also have shown that apolipoprotein a1 is involved in
      triglyceride (TG) metabolism, the mechanisms by which apolipoprotein a1 modulates
      TG levels remain largely unexplored. Here we demonstrated that apolipoprotein a1
      increased mitochondrial DNA and mitochondria contents through sustained AMPK
      activation in myotubes. This resulted in enhanced fatty acid oxidation and
      attenuation of free fatty acid-induced insulin resistance features in skeletal
      muscle. The increment of mitochondria was mediated through induction of
      transcription factors, such as peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha (PGC-1alpha) and nuclear transcription factor 1 (NRF-1). The
      inhibition of AMPK by a pharmacological agent inhibited the induction of
      mitochondrial biogenesis. Increase of AMPK phosphorylation by apolipoprotein a1
      occurs through activation of upstream kinase LKB1. Finally, we confirmed that
      scavenger receptor Class B, type 1 (SR-B1) is an important receptor for
      apolipoprotein a1 in stimulating AMPK pathway and mitochondrial biogenesis. Our
      study suggests that apolipoprotein a1 can alleviate obesity related metabolic
      disease by inducing AMPK dependent mitochondrial biogenesis. 

PMID- 25982509
TI  - Inhibition of glutamate regulated calcium entry into leukemic megakaryoblasts
      reduces cell proliferation and supports differentiation.
AB  - Human megakaryocytes release glutamate and express glutamate-gated Ca(2+)
      permeable N-methyl-D-aspartate receptors (NMDARs) that support megakaryocytic
      maturation. While deregulated glutamate pathways impact oncogenicity in some
      cancers, the role of glutamate and NMDARs in megakaryocytic malignancies remains
      unknown. The aim of this study was to determine if NMDARs participate in Ca(2+)
      responses in leukemic megakaryoblasts and if so, whether modulating NMDAR
      activity could influence cell growth. Three human cell lines, Meg-01, Set-2 and K
      562 were used as models of leukemic megakaryoblasts. NMDAR components were
      examined in leukemic cells and human bone marrow, including in megakaryocytic
      disease. Well-established NMDAR modulators (agonists and antagonists) were
      employed to determine NMDAR effects on Ca(2+) flux, cell viability, proliferation
      and differentiation. Leukemic megakaryoblasts contained combinations of NMDAR
      subunits that differed from normal bone marrow and the brain. NMDAR agonists
      facilitated Ca(2+) entry into Meg-01 cells, amplified Ca(2+) responses to
      adenosine diphosphate (ADP) and promoted growth of Meg-01, Set-2 and K-562 cells.
      Low concentrations of NMDAR inhibitors (riluzole, memantine, MK-801 and AP5; 5
      100MUM) were weakly cytotoxic but mainly reduced cell numbers by suppressing
      proliferation. The use-dependent NMDAR inhibitor, memantine (100MUM), reduced
      numbers and proliferation of Meg-01 cells to less than 20% of controls (IC50
      20MUM and 36MUM, respectively). In the presence of NMDAR inhibitors cells
      acquired morphologic and immunophenotypic features of megakaryocytic
      differentiation. In conclusion, NMDARs provide a novel pathway for Ca(2+) entry
      into leukemic megakaryoblasts that supports cell proliferation but not
      differentiation. NMDAR inhibitors counteract these effects, suggesting a novel
      opportunity to modulate growth of leukemic megakaryoblasts. 

PMID- 25982510
TI  - Conditionally replicating HIV and SIV variants.
AB  - Conditionally replicating human immunodeficiency virus (HIV) and simian
      immunodeficiency virus (SIV) variants that can be switched on and off at will are
      attractive tools for HIV and SIV research. We constructed HIV and SIV variants in
      which the natural transcription control mechanism was replaced by the doxycycline
      (dox)-inducible Tet-On gene expression mechanism. These HIV-rtTA and SIV-rtTA
      variants are fully replication-competent, but replication is critically dependent
      on dox administration. We here describe how the dox-dependent virus variants may
      improve the safety of live-attenuated virus vaccines and how they can be used to
      study the immune responses that correlate with vaccine-induced protection.
      Furthermore, we review how these variants were initially designed and
      subsequently optimized by spontaneous viral evolution. These efforts yielded
      efficiently replicating and tightly dox-controlled HIV-rtTA and SIV-rtTA variants
      that replicate in a variety of cell and tissue culture systems, and in human
      immune system (HIS) mice and macaques, respectively. These viruses can be used as
      a tool in HIV and SIV biology studies and in vaccine research. We review how HIV
      rtTA and SIV-rtTA were used to study the role of the viral TAR and Tat elements
      in virus replication. 

PMID- 25982511
TI  - Identification of miRNAs Involved in the Protective Effect of Sevoflurane
      Preconditioning Against Hypoxic Injury in PC12 Cells.
AB  - The mechanism of sevoflurane preconditioning-induced neuroprotection is poorly
      understood. This study was aimed at identifying microRNAs (miRNAs) involved in
      the protective effect of sevoflurane preconditioning against hypoxic injury using
      the miRCURYTM LNA Array. The screened differentially expressed miRNAs were
      further validated using qRT-PCR. Finally, after transfection of miRNA (miR-101a
      or miR-34b) mimics or inhibitor, MTT and flow cytometry assays were used to
      evaluate cell survival and apoptosis in sevoflurane preconditioning. qRT-PCR
      confirmed the changes in expression of differentially expressed miRNAs that were
      screened by the microarray: down-regulation of rno-miR-101a, rno-miR-106b, and
      rno-miR-294 and up-regulation of rno-miR-883, rno-miR-16, and rno-miR-34b. MiR
      101a and miR-34b were the most differentially expressed miRNAs. Sevoflurane
      preconditioning-inhibited apoptosis and preconditioning-enhanced cell viability
      of PC12 cells were significantly attenuated by transfection of miR-101a mimetic
      or miR-34b inhibitors, but were significantly enhanced by transfection of miR-34b
      mimetic. Therefore, a number of miRNAs, including miR-101a and miR-34b, might
      play important roles in the neuroprotection induced by sevoflurane
      preconditioning. Such miRNAs might provide novel targets for preventive and
      therapeutic strategies against cerebral ischemia-reperfusion injury.

PMID- 25982512
TI  - Chronic Cerebral Ischemia Induces Downregulation of A1 Adenosine Receptors During
      White Matter Damage in Adult Mice.
AB  - The role of A1 adenosine receptors (A1ARs) in the white matter under chronic
      cerebral ischemic conditions remains unclear. Here, we used right unilateral
      common carotid artery occlusion (rUCCAO) to construct a chronic cerebral ischemic
      mouse model. A1AR expression and proteolipid protein (PLP, a marker of white
      matter myelination) in the corpus callosum were observed by immunoreaction and
      immunohistochemistry, respectively. Pro-inflammatory interleukin-1beta (IL-1beta)
      and anti-inflammatory interleukin-10 (IL-10) levels were determined by ELISA. The
      Morris water maze test was employed to detect cognitive impairment. A1AR
      expression significantly decreased in the rUCCAO group as compared with the sham
      control group on weeks 2, 4, and 6, respectively. IL-10 levels in the rUCCAO
      group significantly declined on week 6, while there was no significant change in
      IL-1beta expression. PLP expression significantly decreased in the rUCCAO group
      on weeks 2, 4, and 6. Moreover, latency time for the Morris water maze test
      significantly increased in the rUCCAO group on weeks 4 and 6, while the number of
      platform location crossing significantly decreased in the rUCCAO group on weeks
      2, 4, and 6. In conclusion, this study provides the first evidence that chronic
      cerebral ischemia appears to induce A1AR downregulation and inhibition of IL-10
      production, which may play key roles in the neuropathological mechanisms of
      ischemic white matter lesions. These data will facilitate future studies in
      formulating effective therapeutic strategies for ischemic white matter lesions.

PMID- 25982513
TI  - Loss of TSS1 in hypervirulent Coxiella burnetii 175, the causative agent of Q
      fever in French Guiana.
AB  - In French Guiana, the unique Coxiella burnetii circulating genotype 17 causes 24%
      of community-acquired pneumonia, the highest prevalence ever described. To
      explain this unusual virulence, we performed a comparative genomic analysis of
      strain Cb175, which was isolated from a patient from French Guiana. Cb175 has a
      greater number of mutations in genes involved in metabolism compared with the
      Nine Mile I strain. We found a 6105bp fragment missing in Cb175, which
      corresponds to the Type 1 secretion systems (T1SS) hlyCABD operon region. This
      deletion was detected by a specific qPCR in the 8 other strains available from
      this territory an in none of 298C.burnetii strains from other areas and other
      genotypes (8/8 vs 0/298, Fisher's exact test, p<0.0000001). Loss of genes
      implicated in secretion systems has been observed in other epidemic bacterial
      strains. Thus, the virulence of Cb175 may be linked to this genome reduction. 

PMID- 25982514
TI  - Maternal obesity and development of the preterm newborn at 2 years.
AB  - AIM: To evaluate to what extent extremely preterm children (<28 weeks'
      gestational age) of overweight (BMI 25-29) or obese (BMI >=30) women are at
      increased risk of adverse development at 2 years measured with the Bayley Scales
      of Infant Development II in a multicenter prospective cohort study. METHODS:
      Heights and prepregnancy weights of the mothers of 852 preterm born children were
      collected and included in multinomial logistic regression models. RESULTS:
      Compared to newborns born to mothers with normal BMIs, newborns of obese mothers,
      but not those of overweight mothers, were more likely to have Bayley Scales
      indices more than 3 standard deviations below the reference mean (mental: OR =
      2.1; 95% CI: 1.3, 3.5) (motor: OR = 1.7; 95% CI: 1.1, 2.7). These associations
      were even more prominent in children who did not have the intermittent or
      sustained systemic inflammation profile previously shown to be associated with
      severely impaired development (mental: OR = 4.6; 95% CI: 1.6, 14) (motor: OR =
      3.7; 95% CI: 1.5, 8.9). CONCLUSION: Maternal obesity is associated with an
      increased risk of impaired offspring development. Some of this impaired
      development cannot be attributed to confounding due to immaturity, socio-economic
      correlates or neonatal systemic inflammation.

PMID- 25982517
TI  - Treating acute pancreatitis: what's new?
AB  - The medical treatment of acute pancreatitis continues to focus on supportive
      care, including fluid therapy, nutrition, and antibiotics, all of which will be
      critically reviewed. Pharmacologic agents that were previously studied were found
      to be ineffective likely due to a combination of their targets and flaws in trial
      design. Potential future pharmacologic agents, particularly those that target
      intracellular calcium signaling, as well as considerations for trial design will
      be discussed. As the incidence of acute pancreatitis continues to increase,
      greater efforts will be needed to prevent hospitalization, readmission and
      excessive imaging in order to reduce overall healthcare costs. Primary prevention
      continues to focus on post-endoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis and secondary prevention on cholecystectomy for biliary pancreatitis
      as well as alcohol and smoking abstinence. 

PMID- 25982515
TI  - Overcoming the effects of false positives and threshold bias in graph theoretical
      analyses of neuroimaging data.
AB  - Graph theory (GT) is a powerful framework for quantifying topological features of
      neuroimaging-derived functional and structural networks. However, false positive
      (FP) connections arise frequently and influence the inferred topology of
      networks. Thresholding is often used to overcome this problem, but an appropriate
      threshold often relies on a priori assumptions, which will alter inferred network
      topologies. Four common network metrics (global efficiency, mean clustering
      coefficient, mean betweenness and smallworldness) were tested using a model
      tractography dataset. It was found that all four network metrics were
      significantly affected even by just one FP. Results also show that thresholding
      effectively dampens the impact of FPs, but at the expense of adding significant
      bias to network metrics. In a larger number (n=248) of tractography datasets,
      statistics were computed across random group permutations for a range of
      thresholds, revealing that statistics for network metrics varied significantly
      more than for non-network metrics (i.e., number of streamlines and number of
      edges). Varying degrees of network atrophy were introduced artificially to half
      the datasets, to test sensitivity to genuine group differences. For some network
      metrics, this atrophy was detected as significant (p<0.05, determined using
      permutation testing) only across a limited range of thresholds. We propose a
      multi-threshold permutation correction (MTPC) method, based on the cluster
      enhanced permutation correction approach, to identify sustained significant
      effects across clusters of thresholds. This approach minimises requirements to
      determine a single threshold a priori. We demonstrate improved sensitivity of
      MTPC-corrected metrics to genuine group effects compared to an existing approach
      and demonstrate the use of MTPC on a previously published network analysis of
      tractography data derived from a clinical population. In conclusion, we show that
      there are large biases and instability induced by thresholding, making
      statistical comparisons of network metrics difficult. However, by testing for
      effects across multiple thresholds using MTPC, true group differences can be
      robustly identified. 

PMID- 25982516
TI  - The Image and Data Archive at the Laboratory of Neuro Imaging.
AB  - The LONI Image and Data Archive (IDA)(1) is a repository for sharing and long
      term preservation of neuroimaging and biomedical research data. Originally
      designed to archive strictly medical image files, the IDA has evolved over the
      last ten years and now encompasses the storage and dissemination of neuroimaging,
      clinical, biospecimen, and genetic data. In this article, we report upon the
      genesis of the IDA and how it currently securely manages data and protects data
      ownership. 

PMID- 25982518
TI  - Aldolases Utilize Different Oligomeric States To Preserve Their Functional
      Dynamics.
AB  - Aldolases are essential enzymes in the glycolysis pathway and catalyze the
      reaction cleaving fructose/tagatose 1,6-bisphosphate into dihydroxyacetone
      phosphate and glyceraldehyde 3-phosphate. To determine how the aldolase motions
      relate to its catalytic process, we studied the dynamics of three different class
      II aldolase structures through simulations. We employed coarse-grained elastic
      network normal-mode analyses to investigate the dynamics of Escherichia coli
      fructose 1,6-bisphosphate aldolase, E. coli tagatose 1,6-bisphosphate aldolase,
      and Thermus aquaticus fructose 1,6-bisphosphate aldolase and compared their
      motions in different oligomeric states. The first one is a dimer, and the second
      and third are tetramers. Our analyses suggest that oligomerization not only
      stabilizes the aldolase structures, showing fewer fluctuations at the subunit
      interfaces, but also allows the enzyme to achieve the required dynamics for its
      functional loops. The essential mobility of these loops in the functional
      oligomeric states can facilitate the enzymatic mechanism, substrate recruitment
      in the open state, bringing the catalytic residues into their required
      configuration in the closed bound state, and moving back to the open state to
      release the catalytic products and repositioning the enzyme for its next
      catalytic cycle. These findings suggest that the aldolase global motions are
      conserved among aldolases having different oligomeric states to preserve its
      catalytic mechanism. The coarse-grained approaches taken permit an unprecedented
      view of the changes in the structural dynamics and how these relate to the
      critical structural stabilities essential for catalysis. The results are
      supported by experimental findings from many previous studies. 

PMID- 25982520
TI  - Adult plasticity of cold tolerance in a continental-temperate population of
      Drosophila suzukii.
AB  - Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a worldwide emerging
      pest of soft fruits, but its cold tolerance has not been thoroughly explored. We
      determined the cold tolerance strategy, low temperature thermal limits, and
      plasticity of cold tolerance in both male and female adult D. suzukii. We reared
      flies under common conditions (long days, 21 degrees C; control) and induced
      plasticity by rapid cold-hardening (RCH, 1h at 0 degrees C followed by 1h
      recovery), cold acclimation (CA, 5 days at 6 degrees C) or acclimation under
      fluctuating temperatures (FA). D. suzukii had supercooling points (SCPs) between 
      16 and -23 degrees C, and were chill-susceptible. 80% of control flies were
      killed after 1h at -7.2 degrees C (males) or -7.5 degrees C (females); CA and FA
      improved survival of this temperature in both sexes, but RCH did not. 80% of
      control flies were killed after 70 h (male) or 92 h (female) at 0 degrees C, and
      FA shifted this to 112 h (males) and 165 h (females). FA flies entered chill coma
      (CTmin) at approximately -1.7 degrees C, which was ca. 0.5 degrees C colder than
      control flies; RCH and CA increased the CTmin compared to controls. Control and
      RCH flies exposed to 0 degrees C for 8h took 30-40 min to recover movement, but
      this was reduced to <10 min in CA and FA. Flies placed outside in a field cage in
      London, Ontario, were all killed by a transient cold snap in December. We
      conclude that adult phenotypic plasticity is not sufficient to allow D. suzukii
      to overwinter in temperate habitats, and suggest that flies could overwinter in
      association with built structures, or that there may be additional cold tolerance
      imparted by developmental plasticity.

PMID- 25982519
TI  - Effect of novel restorative materials and retention slots on fracture resistance
      of endodontically-treated teeth.
AB  - OBJECTIVES: The aim of this study was to evaluate the fracture resistance of
      endodontically-treated teeth restored with nano-hybrid composite resin, bulk-fill
      flowable and short fibre-reinforced-composite in the absence/presence of
      retention slots. MATERIALS AND METHODS: One hundred and ten extracted non-carious
      human mandibular molars received endodontic treatment followed by mesio
      occlusodistal (MOD) cavities with 3 +/- 0.2 mm thicknesses of buccal and lingual
      walls. Teeth were divided into two main groups according to the retention slot
      preparation. The dove-tail retention slots were prepared on the middle of
      opposite buccal and lingual walls to create mechanical interlocking. Each group
      was further divided into four sub-groups according to restorative material types:
      control (no restoration), nano-hybrid composite resin (FiltekTM Z550), bulk-fill
      flowable (FiltekTM Bulk Fill) and short fibre-reinforced-composite (everX
      PosteriorTM). Restored teeth were subjected to compressive load at a strain rate
      of 1 mm/min. The data were statistically analysed using two-way ANOVA and Tukey's
      test for multiple comparisons. RESULTS: The fracture resistance was significantly
      affected by the presence of the retentive slots and restorative material (p <
      0.05). Restored teeth with retentive slots significantly increased the fracture
      resistance compared with restored teeth without retentive slots (p < 0.05). Short
      fibre-reinforced-composite with retentive slot cavities had significantly higher
      fracture resistance values compared with the other test groups (p < 0.05).
      CONCLUSIONS: The preparation of retention slots may increase the fracture
      resistance of endodontically-treated teeth, especially, when restored with short
      fibre-reinforced composite. The use of short fibre-reinforced composite with
      retentive slots could be an alternative technique to prevent cuspal fracture on
      endodontically-treated teeth with MOD cavity.

PMID- 25982521
TI  - The pleiotropic allatoregulatory neuropeptides and their receptors: A mini
      review.
AB  - Juvenile hormones (JH) are highly pleiotropic insect hormones essential for post
      embryonic development. The circulating JH titer in the hemolymph of insects is
      influenced by enzymatic degradation, binding to JH carrier proteins, uptake and
      storage in target organs, but evidently also by rates of production at its site
      of synthesis, the corpora allata (CA). The multiple processes in which JH is
      involved alongside the critical significance of JH in insect development
      emphasize the importance for elucidating the control of JH production. Production
      of JH in CA cells is regulated by different factors: by neurotransmitters, such
      as dopamine and glutamate, but also by allatoregulatory neuropeptides originating
      from the brain and axonally transported to the CA where they bind to their G
      protein-coupled receptors (GPCRs). Different classes of allatoregulatory peptides
      exist which have other functions aside from acting as influencers of JH
      production. These pleiotropic neuropeptides regulate different processes in
      different insect orders. In this mini-review, we will give an overview of
      allatotropins and allatostatins, and their recently characterized GPCRs with a
      view to better understand their modes of action and different action sites. 

PMID- 25982522
TI  - Outcomes when congenital heart disease is diagnosed antenatally versus
      postnatally in the UK: a retrospective population-based study.
AB  - BACKGROUND: For major congenital heart disease, the benefits of antenatal
      diagnosis on some post-natal measures have been suggested. However, findings have
      been inconclusive and focus on short term outcome measures alone with little data
      from a UK population. Our aim is to describe differences in reported outcomes for
      patients born with isolated Hypoplastic Left Heart Syndrome or Transposition of
      the Great Arteries in a UK population, following either antenatal or postnatal
      diagnosis. METHODS: Retrospective population-based study with case note review
      covering a 15 year period (1st January 1998 to 31st December 2012) in the British
      county of Leicestershire. Cases were identified from two local registers: the
      East Midlands and South Yorkshire Congenital Anomaly Register and a list of
      surgical patient held by the East Midlands Congenital Heart Centre. RESULTS: In
      total 52 cases of Hypoplastic Left Heart Syndrome or Transposition of the Great
      Arteries were identified with 24 (46.2%) diagnosed antenatally. Maximum and
      minimum follow up was 181 and 16 months respectively. Median follow up was 83
      months (IQR: 44-111). The risk of intubation in the postnatal period (OR: 4.64,
      95% CI: 1.40 - 15.32) was greater in cases of Hypoplastic Left Heart Syndrome or
      Transposition of the Great Arteries diagnosed after birth when compared to those
      diagnosed antenatally. There was a non-significant increase in the risk of
      metabolic acidosis in the postnatal period (OR: 12.5, 95% CI: 0.64 - 245.46). No
      differences in mortality or long-term outcomes were demonstrated between
      antenatally and postnatally diagnosed cohorts. CONCLUSIONS: These results confirm
      data from American and European populations that, for a British population, an
      antenatal diagnosis of a major congenital heart disease can have a favourable
      impact on some postnatal outcome measures. There appears to be no evidence that
      time of diagnosis impacts on long-term outcome measures.

PMID- 25982523
TI  - Pharmacokinetics of cefuroxime after intravenous, intramuscular, and subcutaneous
      administration to dogs.
AB  - Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single
      intravenous, intramuscular, and subcutaneous administration at a dosage of 20
      mg/kg. Blood samples were withdrawn at predetermined times over a 12-h period.
      Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by
      compartmental analysis. Peak plasma concentration (Cmax ), time-to-peak plasma
      concentration (Tmax ), and bioavailability for the intramuscular and subcutaneous
      administration were (mean +/- SD) 22.99 +/- 7.87 MUg/mL, 0.43 +/- 0.20 h, and
      79.70 +/- 14.43% and 15.37 +/- 3.07 MUg/mL, 0.99 +/- 0.10 h, and 77.22 +/-
      21.41%, respectively. Elimination half-lives and mean residence time for the
      intravenous, intramuscular, and subcutaneous administration were 1.12 +/- 0.19 h
      and 1.49 +/- 0.21 h; 1.13 +/- 0.13 and 1.79 +/- 0.24 h; and 1.04 +/- 0.23 h and
      2.21 +/- 0.23 h, respectively. Significant differences were found between routes
      for Ka , MAT, Cmax , Tmax , t1/2(a) , and MRT. T > MIC = 50%, considering a MIC
      of 1 MUg/mL, was 11 h for intravenous and intramuscular administration and 12 h
      for the subcutaneous route. When a MIC of 4 MUg/mL is considered, T > MIC = 50%
      for intramuscular and subcutaneous administration was estimated in 8 h.

PMID- 25982524
TI  - [Tamsulosin efficacy and safety for conservative management of renal colic:
      systematic review and meta-analysis of randomized controlled trials].
AB  - BACKGROUND AND OBJECTIVE: The aim is to evaluate tamsulosin efficacy and safety
      on the expulsion of distal ureteral stones compared to a standard therapy.
      MATERIAL AND METHODS: Systematic searches were conducted on PubMed, SCOPUS and
      The Cochrane Library so as to identify randomized and controlled clinical trials
      in patients treated with tamsulosin with ureteral stone expulsion and adverse
      events published until 2014 December, without language restriction. Treatment
      effect was calculated along with the 95% confidence interval (95% CI), using the
      variance inverse method for random effects. Heterogeneity was determined by I(2).
      Publication bias was assessed by Egger test. RESULTS: The search identified 480
      articles. Thirty-eight met the selection criteria, a total of 3,107 patients. The
      relative risk (RR) of expulsion was 1.53 (95% CI 1.38-1.69; I(2)=71%.), while the
      RR of adverse effects was 1.79 (95% CI 1.19-2,71; I(2)=0). CONCLUSIONS:
      Tamsulosin treatment seems to bring on the expulsion of distal ureteral stones,
      although at the expense of an appreciable risk of side effects.

PMID- 25982525
TI  - A Comparison of Human Narrative Coding of Redemption and Automated Linguistic
      Analysis for Understanding Life Stories.
AB  - The majority of life narrative research is performed using trained human coders.
      In contrast, automated linguistic analysis is oft employed in the study of verbal
      behaviors. These two methodological approaches are directly compared to determine
      the utility of automated linguistic analysis for the study of life narratives. In
      a study of in-person interviews (N = 158) and a second study of life stories
      collected online (N = 242), redemption scores are compared to the output of the
      Linguistic Inquiry and Word Count (Pennebaker, Francis & Booth, 2001).
      Additionally, patterns of language are found using exploratory principal
      components analysis. In both studies, redemption scores are modestly correlated
      with some LIWC categories and unassociated with the components. Patterns of
      language do not replicate across samples, indicating that the structure of
      language does not extend to a broader population. Redemption scores and
      linguistic components are independent predictors of life satisfaction up to 3
      years later. These studies converge on the finding that human-coded redemption
      and automated linguistic analysis are complementary and nonredundant methods of
      analyzing life narratives, and considerations for the study of life narratives
      are discussed.

PMID- 25982526
TI  - A Mimivirus Enzyme that Participates in Viral Entry.
AB  - Mimivirus was initially identified as a bacterium because its dense, 125-nm-long
      fibers stained Gram-positively. These fibers probably play a role during the
      infection of some host cells. The normal hosts of Mimivirus are unknown, but in
      the laboratory Mimivirus is usually propagated in amoeba. The structure of R135,
      a major component of the fibrous outer layer of Mimivirus, has been determined to
      2-A resolution. The protein's structure is similar to that of members of the
      glucose-methanol-choline oxidoreductase family, which have an N-terminal FAD
      binding domain and a C-terminal substrate recognition domain. The closest homolog
      to R135 is an aryl-alcohol oxidase that participates in lignin biodegradation of
      plant cell walls. Thus R135 might participate in the degradation of their normal
      hosts, including some lignin-containing algae. 

PMID- 25982527
TI  - Structural Insights into the Molecular Recognition between Cerebral Cavernous
      Malformation 2 and Mitogen-Activated Protein Kinase Kinase Kinase 3.
AB  - Cerebral cavernous malformation 2 (CCM2) functions as an adaptor protein
      implicated in various biological processes. By interacting with the mitogen
      activated protein kinase MEKK3, CCM2 either mediates the activation of MEKK3
      signaling in response to osmotic stress or negatively regulates MEKK3 signaling,
      which is important for normal cardiovascular development. However, the molecular
      basis governing CCM2-MEKK3 interaction is largely unknown. Here we report the
      crystal structure of the CCM2 C-terminal part (CCM2ct) containing both the five
      helix domain (CCM2cts) and the following C-terminal tail. The end of the C
      terminal tail forms an isolated helix, which interacts intramolecularly with
      CCM2cts. By biochemical studies we identified the N-terminal amphiphilic helix of
      MEKK3 (MEKK3-nhelix) as the essential structural element for CCM2ct binding. We
      further determined the crystal structure of CCM2cts-MEKK3-nhelix complex, in
      which MEKK3-nhelix binds to the same site of CCM2cts for CCM2ct intramolecular
      interaction. These findings build a structural framework for understanding CCM2ct
      MEKK3 molecular recognition. 

PMID- 25982529
TI  - Efficient estimation of three-dimensional covariance and its application in the
      analysis of heterogeneous samples in cryo-electron microscopy.
AB  - Single-particle cryogenic electron microscopy (cryo-EM) is a powerful tool for
      the study of macromolecular structures at high resolution. Classification allows
      multiple structural states to be extracted and reconstructed from the same
      sample. One classification approach is via the covariance matrix, which captures
      the correlation between every pair of voxels. Earlier approaches employ computing
      intensive resampling and estimate only the eigenvectors of the matrix, which are
      then used in a separate fast classification step. We propose an iterative scheme
      to explicitly estimate the covariance matrix in its entirety. In our approach,
      the flexibility in choosing the solution domain allows us to examine a part of
      the molecule in greater detail. Three-dimensional covariance maps obtained in
      this way from experimental data (cryo-EM images of the eukaryotic pre-initiation
      complex) prove to be in excellent agreement with conclusions derived by using
      traditional approaches, revealing in addition the interdependencies of ligand
      bindings and structural changes. 

PMID- 25982528
TI  - Signal transduction in histidine kinases: insights from new structures.
AB  - Histidine kinases (HKs) are major players in bacterial signaling. There has been
      an explosion of new HK crystal structures in the last 5 years. We globally
      analyze the structures of HKs to yield insights into the mechanisms by which
      signals are transmitted to and across protein structures in this family. We
      interpret known enzymological data in the context of new structural data to show
      how asymmetry across the dimer interface is a key feature of signal transduction
      in HKs, and discuss how different HK domains undergo asymmetric to symmetric
      transitions during signal transduction and catalysis. A thermodynamic framework
      for signaling that encompasses these various properties is presented, and the
      consequences of weak thermodynamic coupling are discussed. The synthesis of
      observations from enzymology, structural biology, protein engineering, and
      thermodynamics paves the way for a deeper molecular understanding of HK signal
      transduction. 

PMID- 25982530
TI  - Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate
      Ligands.
AB  - Interactions of the chemokine CCL5 (RANTES) with glycosaminoglycans (GAGs) are
      crucial to the CCL5-mediated inflammation process. However, structural
      information on interactions between CCL5 and longer GAG fragments is lacking. In
      this study, the interactions between oligosaccharides derived from chondroitin
      sulfate and a dimeric variant of CCL5 were investigated using solution nuclear
      magnetic resonance. The data indicate that, in addition to the BBXB motif in the
      40s loop, GAGs also contact residues in the N loop in a manner similar to
      interactions between chemokine and the receptor N terminus, leading to possible
      stabilization of the dimer. Using 2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl
      tagged hexasaccharides, the binding orientation of the hexasaccharides was shown
      to be highly dependent on the sulfation pattern of the N-acetyl galactosamine
      groups. Finally, a model of the CCL5 dimer complexed to chondroitin sulfate
      hexasaccharides was constructed using paramagnetic relaxation enhancement and
      intra- and intermolecular nuclear Overhauser effect constraints. 

PMID- 25982531
TI  - 'There's a letter called ef' on Challenges and Repair in Interpreter-Mediated
      Tests of Cognitive Functioning in Dementia Evaluations: A Case Study.
AB  - In the Scandinavian countries Sweden, Denmark, Norway, and Finland, the number of
      first generation migrants reaching an old age, who will be in need of age-related
      health-care, is rapidly increasing. This situation poses new demands on health
      care facilities, such as memory clinics, where patients with memory problems and
      other dementia symptoms are referred for examination and evaluation. Very many
      elderly people with a foreign background require the assistance of an interpreter
      in their encounter with health-care facilities. The use of, and work by an
      interpreter is crucial in facilitating a smooth assessment. However,
      interpreters, clinicians, as well as patients and their companions, may be faced
      with many challenges during the evaluation procedure. The aim of this case-study
      is to highlight some of the challenges that occur in relation to a specific
      activity within the dementia evaluation, namely the test of cognitive
      functioning. Special attention will be paid to the phenomenon 'repair', i.e.,
      participants' joint attempts to solve upcoming difficulties during the course of
      interaction. Results show that sources of trouble may be related to the lack of
      cultural, linguistic, and educational adaptation of the test to the patient, and
      to interpreter and clinician practises. Findings will be discussed in terms of
      test-validity, clinician and interpreter training, and the institutional goals
      and constraints of the dementia evaluation. The methodology Conversation Analysis
      has been used to conduct a highly detailed analysis of participants' practices
      and actions during the administration of the test. 

PMID- 25982532
TI  - Loneliness of Older Immigrant Groups in Canada: Effects of Ethnic-Cultural
      Background.
AB  - This study aimed to explore the loneliness of several groups of older immigrants
      in Canada compared to native-born older adults. Data from the Canadian General
      Social Survey, Cycle 22 (N older adults = 3,692) were used. The dependent
      variable is the 6 item De Jong Gierveld loneliness scale. Determinants of
      loneliness included country of birth, ethnic background (cultural context);
      belongingness (community context) and social networks (social context). Results
      showed that only some immigrant groups are significantly lonelier than older
      adults born in Canada. Immigrants with similar language and culture are not
      lonelier; while those from countries that differ in native language/culture are
      significantly higher on loneliness. Multivariate analyses showed the importance
      of cultural background, of composition of the network of relatives and friends,
      and of local participation and feelings of belonging to the Canadian society in
      explaining loneliness of older immigrants. 

PMID- 25982533
TI  - Bring stem cell therapies to cure intervertebral disc degeneration to the
      forefront.

PMID- 25982534
TI  - Isolation and characterization of meniscus derived stem cells from rabbit as a
      possible treatment for damaged meniscus.
AB  - BACKGROUND: The successful surgical restoration of damaged meniscus has been a
      challenge, largely owing to a lack of characterization of meniscus cells and
      their precursors. Numerous strategies to repair or replace meniscus have achieved
      only limited success. Several recent studies have shown beneficial effect of
      mesenchymal stem cells in meniscus repair. The objective of our study was to
      characterize meniscus derived mesenchymal stem cells in terms of, colony
      formation, proliferation, multi potency and self-renewal capacity. METHODS:
      Mesenchymal stem cells were isolated from menisci, patellar tendon and bone
      marrow of rabbits. The multi differentiating potential, colony, morphology and
      proliferation were studied in vitro. The expression of differential markers was
      studied by immunocytochemistry, qPCR and western blotting. RESULTS: Three groups
      of cells appeared similar in colony formation and morphology. All of them were
      found to express high levels of stem cell markers including SSEA-4, Nanog and
      nucleostemin. High level of collagen II expression was detected in meniscus
      derived stem cells. Moreover, these cells appeared to have a pronounced tendency
      to chondrogenic differentiation under specialized culture conditions.
      CONCLUSIONS: Meniscus-derived mesenchymal stem cells (MMSCs) possessed all the
      necessary criteria of stem cells, including clonogenicity, self-renewal and
      multipotent differentiation capacity and possessed a tendency to differentiate
      into chondrocytes. Our results offer new insights into the biology of meniscus
      cells, and may assist in future strategies to treat damaged meniscus.

PMID- 25982535
TI  - QuantiGene Plex Represents a Promising Diagnostic Tool for Cell-of-Origin
      Subtyping of Diffuse Large B-Cell Lymphoma.
AB  - Emerging therapies targeting the molecularly distinct GCB and non-GCB/ABC
      subtypes of diffuse large B-cell lymphoma (DLBCL) have created the need to
      develop an accurate subtyping assay for routine use. We investigated the
      potential of QuantiGene Plex (QGP)-branched DNA signal amplification assay-for
      DLBCL subtyping. We performed in silico analysis of public DLBCL datasets to
      develop and validate a naive Bayes classifier, and migrated the resulting 21-gene
      classifier to QGP and real-time quantitative PCR (qPCR) assays. Forty DLBCL
      formalin-fixed, paraffin-embedded tumors of known subtype (20 per subtype by gene
      expression profiling of paired fresh-frozen tissues) were reclassified, and
      results for QGP (on 38/40 for 21/21 targets) and qPCR (on 40/40 samples for 19/21
      targets) compared for recapitulation of microarray data and classification
      accuracy. The 21-gene bayesian classifier achieved mean area under the curve
      values >0.9 on independent validation. QGP showed a higher correlation with
      microarray data (mean R(2) = 0.66 +/- 0.05 versus 0.34 +/- 0.07; P < 0.0001) and
      classification accuracy (92.1% versus 78.9%). The proportion of validated targets
      was also higher for QGP (85.7% versus 47.4%). The QGP protocol was rapid and
      simple to perform, at a cost similar to qPCR. These promising preliminary results
      strongly support ongoing work to develop a QGP companion diagnostic assay for
      DLBCL subtyping.

PMID- 25982536
TI  - Acid Chloride Synthesis by the Palladium-Catalyzed Chlorocarbonylation of Aryl
      Bromides.
AB  - We report a palladium-catalyzed method to synthesize acid chlorides by the
      chlorocarbonylation of aryl bromides. Mechanistic studies suggest the combination
      of sterically encumbered PtBu3 and CO coordination to palladium can rapidly
      equilibrate the oxidative addition/reductive elimination of carbon-halogen bonds.
      This provides a useful method to assemble highly reactive acid chlorides from
      stable and available reagents, and can be coupled with subsequent nucleophilic
      reactions to generate new classes of carbonylated products. 

PMID- 25982537
TI  - Impact of Physical Resistance Training on the Sexual Function of Women with
      Polycystic Ovary Syndrome.
AB  - INTRODUCTION: There is a need for specific measures to address overall care in
      women with polycystic ovary syndrome (PCOS). Physical resistance training (PRT)
      has been shown to improve certain body parameters. However, the effect of PRT on
      the sexual function of PCOS women has not been evaluated. AIM: The study aimed to
      assess sexual function and emotional status of PCOS women after 16 weeks of PRT.
      METHODS: This case-control study involved 43 women with PCOS and 51 control
      ovulatory women, aged 18-37 years. All women were subjected to a supervised PRT
      protocol for 16 weeks and evaluated at the end of the program. Sexual function
      was assessed at baseline and after PRT protocol. MAIN OUTCOME MEASURES: The main
      outcome measure used was the Female Sexual Function Index (FSFI). RESULTS: Of the
      43 women with PCOS, 30 (69.70%) had a basal total FSFI score <= 26.55 and 24 of
      them (58.54%) had a score <= 26.55 after PRT (P = 0.08). Of the 51 control women,
      32 (62.7%) and 27 (52.9%) had FSFI scores < 26.55 at baseline and after PRT,
      respectively (P = 0.06). Control women experienced a significant improvement in
      pain domain score after PRT (P < 0.03). PCOS women experienced significant
      increases in total score and in the desire, excitement and lubrication domains
      after PRT (P < 0.01 each). After PRT, there was a significant difference between
      the PCOS and control groups in the sexual desire domain (4.09 +/- 1.29 vs. 3.75
      +/- 1.42, P = 0.04). Significantly fewer women in the PCOS group were at risk of
      depression (P < 0.01) and anxiety (P < 0.02) after than before PRT, whereas the
      differences in the control group were not significant. Mean depression and
      anxiety scores were reduced significantly in both the PCOS (P < 0.01 each) and
      control (P < 0.01) groups. CONCLUSIONS: PRT significantly enhanced total score
      and the desire, excitement, and lubrication domains of the FSFI in PCOS women.
      PRT reduced pain, and total depression and anxiety scores in both groups.

PMID- 25982538
TI  - [Eye injury with an intraocular foreign body].

PMID- 25982539
TI  - Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for
      moderate to severe plaque psoriasis: A randomized, double-blind, noninferiority
      trial (SCULPTURE).
AB  - BACKGROUND: Secukinumab has demonstrated high, sustained efficacy in psoriasis to
      52 weeks on a fixed-interval regimen. OBJECTIVE: We sought to compare a
      retreatment-as-needed versus a fixed-interval regimen. METHODS: In this double
      blind study, adults with moderate to severe plaque psoriasis were randomized 1:1
      to subcutaneous secukinumab at 300 mg (n = 484) or 150 mg (n = 482) weekly from
      baseline until week 4, and at week 8. At week 12, patients achieving 75% or more
      improvement from baseline Psoriasis Area and Severity Index score (PASI 75) were
      rerandomized to 2 dose levels of secukinumab retreatment as needed (n = 217, 300
      mg; n = 206, 150 mg) or fixed interval (n = 217; n = 203). Primary end point was
      noninferiority of retreatment as needed versus fixed interval for maintaining
      PASI 75 to week 52. RESULTS: Secukinumab induced high responses by week 12 (84.4%
      91.1% PASI 75 responders). From week 12 to week 52, more patients on fixed
      interval (78.2%, 300 mg; 62.1%, 150 mg) maintained PASI 75 versus retreatment as
      needed (67.7%; 52.4%); statistical noninferiority of retreatment as needed was
      not established. Overall safety, including very low incidences of treatment
      emergent anti-drug antibodies (<0.5%), was similar between regimens. LIMITATIONS:
      The primary end point was developed without any known precedent. CONCLUSION:
      Secukinumab fixed interval showed clear benefit versus the study-specified
      retreatment-as-needed regimen for maintaining efficacy. Both regimens exhibited
      safety consistent with previous trials. The potential of retreatment as needed
      with secukinumab warrants further investigation.

PMID- 25982540
TI  - Dermoscopy of black skin: A cross-sectional study of clinical and dermoscopic
      features of melanocytic lesions in individuals with type V/VI skin compared to
      those with type I/II skin.
AB  - BACKGROUND: The identification of "normal" dermoscopic patterns of acquired
      melanocytic nevi provides better diagnostic accuracy for melanoma in people with
      black skin. OBJECTIVE: We sought to describe melanocytic lesions (numbers and
      anatomic distributions) in skin types V and VI compared with skin types I and II,
      according to the Fitzpatrick classification. We sought to identify differences in
      dermoscopic findings in acquired melanocytic nevi (global pattern, pigment and
      color distribution) between the groups. METHODS: We conducted cross-sectional,
      prospective, and consecutive data collection in 2 dermatologic outpatient
      clinics, between October 8, 2010, and March 20, 2013. From the 501 volunteers,
      480 participants fulfilled the eligibility criteria. A total of 460 acquired
      melanocytic nevi were selected for dermoscopic analysis. RESULTS: Individuals
      with skin type V/VI had fewer melanocytic lesions than those with skin type I/II
      (15.08 vs 7.90; P = .032), and the anatomic distribution in the first group was
      predominantly on the face and acral sites (P < .001). The acquired melanocytic
      nevi in the skin type V/VI group were associated with the reticular pattern (P <
      .0001), with a tendency toward central hyperpigmentation (P = .0025).
      LIMITATIONS: The choice of a single representative nevus per patient is a
      limitation. CONCLUSIONS: Acquired melanocytic nevi in individuals with skin type
      V/VI have a distinct dermoscopic pattern from those with skin type I/II.

PMID- 25982541
TI  - Synthesis, antimicrobial activity and toxicity of analogs of the scorpion venom
      BmKn peptides.
AB  - Two analogs of the natural peptide BmKn1 and four of BmKn2 found in the venom of
      the scorpion Buthus martensii Karsh have been synthesized and tested to compare
      their antimicrobial and hemolytic activity with the natural ones. Modifications
      of the natural sequence were done on the hydrophobic side of the alpha helix by
      increasing the size and hydrophobicity of the residues with alanine (BmKn2A1),
      valine (BmKn2V1) and leucine (BmKn2L1) respectively, and on the hydrophilic side
      by increasing the charge from +2 to +3 with two lysines (BmKn2K7). In order to
      study observed peptide aggregation, two peptides with one (BmKn1-6Lys) and two
      (BmKn1L2K2) positive charges respectively in the hydrophobic side have been also
      designed. Results show that the valine substituted analog BmKn2V1 and lysine
      substituted analog BmKn2K7 have in general, the highest antibiotic and hemolytic
      activity of the group. Introduction of one positive charge on the hydrophobic
      side shows a significant increase in antibacterial activity compared with the
      original sequence except for Bacillus and Enterobacter where, unexpectedly, the
      activity flats-off. In contrast, the analog with two positive charges has minimal
      antibacterial or hemolytic activity. 

PMID- 25982542
TI  - Debate, Discussion, or Dialogue.

PMID- 25982543
TI  - Holotranscobalamin Levels in Children with Helicobacter pylori Infection.
AB  - BACKGROUND: The purpose of this study was to evaluate the association between
      vitamin B12 levels and Helicobacter Pylori infection and to examine the clinical
      usefulness of holotranscobalamin (holoTC) measurement in children. MATERIALS AND
      METHODS: Thirty patients between 6 and 15 years of age, who were diagnosed as H.
      pylori infected by C(14) urea breath test, and 26 controls were enrolled in the
      study. Tests for complete blood count, serum vitamin B12 and folate, plasma total
      homocysteine, and holoTC levels were performed in each patient in the study and
      control groups. RESULTS: Mean plasma holoTC concentrations were significantly
      lower in children with H. pylori infection before treatment (median 23.7 pmol/L
      (12.9-37.1 pmol/L)) versus after treatment (median 38.2 pmol/L (21.2-61.4
      pmol/L)) and controls (median 36.1 pmol/L (12.6-58.7 pmol/L)). CONCLUSIONS: The
      findings of our study suggest that H. pylori infection has a reversible negative
      effect on vitamin B12 status reflected in a decreased level of plasma holoTC that
      normalizes upon treatment of the infection, while no change is observed in total
      plasma vitamin B12 .

PMID- 25982545
TI  - Colorimetric detection of the flux of hydrogen peroxide released from living
      cells based on the high peroxidase-like catalytic performance of porous PtPd
      nanorods.
AB  - One-dimensional PtPd porous nanorods (PtPd PNRs) were successfully synthesized
      through a bromide-induced galvanic replacement reaction between Pd nanowires and
      K2PtCl6. The PtPd PNRs were porous and alloy-structured with Pt/Pd atomic ratio
      up to 1:1 which were demonstrated by spectroscopic methods. We had also proved
      that the nanorods could function as peroxidase mimetic for the detection of H2O2,
      with the detection limit of 8.6 nM and the linear range from 20 nM to 50 mM. The
      result demonstrated that PtPd PNRs exhibited much higher affinity to H2O2 over
      other peroxidase mimetics due to synergistically integrating highly catalytic
      activity of two metals. On the basis of the peroxidase-like activity, the PtPd
      PNRs were used as a signal transducer to develop a novel and simple colorimetric
      method for the study of the flux of H2O2 released from living cell. By using
      3,3,5,5-tetramethylbenzidine as substrate, the H2O2 concentration could be
      distinguished by naked-eye observation without any instrumentation or complicated
      design. The method developed a new platform for a reliable collection of
      information on cellular reactive oxygen species release. And the nanomaterial
      could be used as a power tool for a wide range of potential applications in
      biotechnology and medicine.

PMID- 25982544
TI  - Evaluating early administration of the hydroxymethylglutaryl-CoA reductase
      inhibitor simvastatin in the prevention and treatment of delirium in critically
      ill ventilated patients (MoDUS trial): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: The incidence of delirium in ventilated patients is estimated at up
      to 82%, and it is associated with longer intensive care and hospital stays, and
      long-term cognitive impairment and mortality. The pathophysiology of delirium has
      been linked with inflammation and neuronal apoptosis. Simvastatin has pleiotropic
      properties; it penetrates the brain and, as well as reducing cholesterol, reduces
      inflammation when used at clinically relevant doses over the short term. This is
      a single centre randomised, controlled trial which aims to test the hypothesis
      that treatment with simvastatin will modify delirium incidence and outcomes.
      METHODS/DESIGN: The ongoing study will include 142 adults admitted to the Watford
      General Hospital Intensive Care Unit who require mechanical ventilation in the
      first 72 hours of admission. The primary outcome is the number of delirium- and
      coma-free days in the first 14 days. Secondary outcomes include incidence of
      delirium, delirium- and coma-free days in the first 28 days, days in delirium and
      in coma at 14 and 28 days, number of ventilator-free days at 28 days, length of
      critical care and hospital stay, mortality, cognitive decline and healthcare
      resource use. Informed consent will be taken from patient's consultee before
      randomisation to receive either simvastatin (80 mg) or placebo once daily. Daily
      data will be recorded until day 28 after randomisation or until discharge from
      the ICU if sooner. Surviving patients will be followed up on at six months from
      discharge. Plasma and urine samples will be taken to investigate the biological
      effect of simvastatin on systemic markers of inflammation, as related to the
      number of delirium- and coma-free days, and the potential of cholinesterase
      activity and beta-amyloid as predictors of the risk of delirium and long-term
      cognitive impairment. DISCUSSION: This trial will test the efficacy of
      simvastatin on reducing delirium in the critically ill. If patients receiving the
      statin show a reduced number of days in delirium compared with the placebo group,
      the inflammatory theory implicated in the pathogenesis of delirium will be
      strengthened. TRIAL REGISTRATION: The trial was registered with the International
      Standard Randomised Controlled Trial Registry ( ISRCTN89079989 ) on 26 March
      2013.

PMID- 25982546
TI  - Toxicokinetics and tissue distribution of cadmium-based Quantum Dots in the
      marine mussel Mytilus galloprovincialis.
AB  - Environmental health hazards of Quantum Dots (QDs) are of emergent concern, but
      limited data is available about their toxicokinetics (TK) and tissue distribution
      in marine bivalves. This study investigated the QDs behavior in seawater, their
      TK and tissue distribution in Mytilus galloprovincialis, in comparison with
      soluble Cd. Mussels were exposed to CdTe QDs and soluble Cd for 21 days at 10
      MUgCd L(-1) followed by a 50 days depuration. TK of QDs in mussels is related to
      the homo-aggregate uptake, surface charge, aggregation and precipitation as key
      factors. There were tissue- and time-dependent differences in the TK of both Cd
      forms, and soluble Cd is the most bioavailable form. Digestive gland is a
      preferential site for QDs storage and both Cd forms are not eliminated by mussels
      (t1/2>50 days). Results indicate that the TK model of CdTe QDs in marine mussels
      is distinct from their soluble counterparts. 

PMID- 25982547
TI  - Pollutant threshold concentration determination in marine ecosystems using an
      ecological interaction endpoint.
AB  - The threshold concentrations of pollutants are determined by extrapolating single
      species effect data to community-level effects. This assumes the most sensitive
      endpoint of the life cycle of individuals and the species sensitivity
      distribution from single-species toxic effect tests, thus, ignoring the
      ecological interactions. The uncertainties due to this extrapolation can be
      partially overcome using the equilibrium point of a customized ecosystem. This
      method incorporates ecological interactions and integrates the effects on growth,
      survival, and ingestion into a single effect measure, the equilibrium point
      excursion in the customized ecosystem, in order to describe the toxic effects on
      plankton. A case study showed that the threshold concentration of copper
      calculated with the endpoint of the equilibrium point was 10 MUg L(-1), which is
      significantly different from the threshold calculated with a single-species
      endpoint. The endpoint calculated using this method provides a more relevant
      measure of the ecological impact than any single individual-level endpoint. 

PMID- 25982548
TI  - Comprehensive evaluation of pharmaceuticals and personal care products (PPCPs) in
      typical highly urbanized regions across China.
AB  - This study evaluated the occurrence of 36 PPCPs in urban river water samples
      collected from Beijing, Changzhou and Shenzhen. Twenty-eight compounds were
      detected. Compounds found with highest median concentrations included:
      sulfadimethoxine (164 ng/L), sulpiride (77.3 ng/L), atenolol (52.9 ng/L), and
      indomethacin (50.9 ng/L). Antibiotic was the predominant class detected and
      contributed about half of the overall PPCPs contamination level. Effluents from
      wastewater treatment plants (WWTPs) were demonstrated to be the predominant
      pathways through which PPCPs entering into aquatic environment in all
      investigated areas. The ratio of persistent PPCPs like sulpiride and
      carbamazepine was identified to be feasible in tracing their contamination
      sources in rivers. Concentrations of most detected PPCPs showed significant
      positive correlations with total nitrogen and total phosphorus. Two groups of
      representative PPCPs were selected as the chemical indicators for predicting the
      overall PPCPs contamination, based on the significant correlations between PPCPs.

PMID- 25982549
TI  - Spatial analysis of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (Sea-Nine 211)
      concentrations and probabilistic risk to marine organisms in Hiroshima Bay,
      Japan.
AB  - We analyzed the spatial distribution of an antifouling biocide, 4,5-dichloro-2-n
      octyl-4-isothiazolin-3-one (Sea-Nine 211) in the surface water and sediments of
      Hiroshima Bay, Japan to determine the extent of contamination by this biocide. A
      quantitative estimate of the environmental concentration distribution (ECD) and
      species sensitivity distributions (SSDs) for marine organisms were derived by
      using a Bayesian statistical model to carry out a probabilistic ecological risk
      analysis, such as calculation of the expected potentially affected fraction
      (EPAF). The spatial distribution analysis supported the notion that Sea-Nine 211
      is used mainly for treatment of ship hulls in Japan. The calculated EPAF suggests
      that approximately up to a maximum of 0.45% of marine species are influenced by
      the toxicity of Sea-Nine 211 in Hiroshima Bay. In addition, estimation of the
      ecological risk with a conventional risk quotient method indicated that the risk
      was a cause for concern in Hiroshima Bay. 

PMID- 25982550
TI  - Cervical Cancer Stigma in Rural Kenya: What Does HIV Have to Do with It?
AB  - Cervical cancer is a leading cause of cancer-related death amongst women in sub
      Saharan Africa, largely due to the lack of early screening and treatment. In
      addition to poor access to screening services, inadequate uptake of available
      services is a barrier to early identification of precancerous lesions. Given that
      cervical cancer is caused by a sexually transmitted virus and is associated with
      HIV positivity, stigma is one of the potential barriers to the utilization of
      cervical cancer programs in sub-Saharan Africa. We conducted a cross-sectional
      survey of 419 women attending health facilities in rural western Kenya to measure
      levels of cervical cancer and HIV stigma and to measure the associations between
      cervical cancer stigma, HIV stigma, and HIV status. Women who qualified for
      cervical cancer screening were asked to complete an oral questionnaire using a
      modified 9-point HIV stigma scale. Low cervical cancer stigma was reported in
      this study, with only 85/419 (20.3 %) of respondents answering yes to at least
      one cervical cancer stigma question. However, cervical cancer stigma was highly
      correlated with HIV stigma (correlation coefficient 0.72) and was significantly
      lower in HIV-positive women (p < 0.001). Reducing cervical cancer stigma in the
      general population is an important part of promoting screening in sub-Saharan
      Africa. 

PMID- 25982551
TI  - Multifunctional gold nanostar-based nanocomposite: Synthesis and application for
      noninvasive MR-SERS imaging-guided photothermal ablation.
AB  - We report here the design and facile synthesis of multifunctional gold nanostars
      based nanocomposites (MGSNs) through direct organosilica coating onto anisotropic
      gold nanostars followed by the conjugation of Gd chelates. The as-synthesized
      MGSNs possess strong NIR absorbance, SERS signal and enhanced T1-MR imaging
      capability with excellent dispersivity and uniform size, as well as great
      photothermal stability and Raman stability under photothermal conditions.
      Importantly, MGSNs present excellent performance in vivo after their intravenous
      injection for both MR and SERS imaging and the high efficiency for killing tumor
      cells through photothermal ablation with NIR irradiation. A combination of the
      high spatial resolution of MR and the exciting sub-cell-level sensitivity and
      resolution of SERS can provide comprehensive information about the tumor to
      achieve the optimized therapeutic outcome. Therefore, MGSNs are of great
      potential as a multifunctional nanoplatform for MR-SERS bimodal imaging-guided,
      focused photothermal tumor therapy. 

PMID- 25982552
TI  - Dual-targeting and pH/redox-responsive multi-layered nanocomplexes for smart co
      delivery of doxorubicin and siRNA.
AB  - Multi-layered nanocomplexes (MLNs) were designed here to provide smart co
      delivery of doxorubicin (DOX) and vascular endothelial growth factor (VEGF)
      siRNA. The electrostatically self-assembled MLNs were constructed by TAT peptide
      modified mesoporous silica nanoparticles (TAT-MSN) as the cationic core for DOX
      loading, poly(allylamine hydrochloride)-citraconic anhydride (PAH-Cit) as the
      anionic inner layer, and galactose-modified trimethyl chitosan-cysteine (GTC)
      conjugate as the cationic outer layer to encapsulate siRNA. Their strong
      stability at pH 7.4 and 6.5 protected siRNA from degradation in the blood and
      tumor microenvironment. Galactose ligands on the GTC outer layers effectively
      facilitated the internalization of MLNs through receptor-mediated endocytosis.
      Afterwards, the endosomal/lysosomal acidity (pH 5.0) triggered the charge
      reversal of PAH-Cit, thereby inducing the disassembly of MLNs and their escape to
      the cytosol. Cytoplasmic glutathione further accelerated siRNA release through
      cleaving disulfide bonds in GTC layers, leading to high silencing efficiencies.
      Meanwhile, the exposed DOX-loaded cores were transported into the nuclei by
      virtue of TAT peptide and exhibited sustained release thereafter. As a result,
      potent antitumor efficacies of MLNs were noted following intravenous injection at
      a low dose with no apparent toxicity detected. Therefore, MLNs served as an
      effective and safe vector to maximize synergistic effect of chemodrugs and
      therapeutic genes. 

PMID- 25982553
TI  - Pentraxin-3 as a local inflammatory marker in chronic spontaneous urticaria.
AB  - BACKGROUND: The pentraxin family plays an important role in the acute phase
      response to immune-inflammatory processes. The short pentraxin, C-reactive
      protein (CRP) is a marker of chronic spontaneous urticaria (CSU) activity,
      reflecting the systemic effects of inflammatory mediators associated with the
      disease. It is known, that the long pentraxin, pentraxin 3 (PTX3) is produced at
      the sites of inflammation, therefore may better reflect activity of the local
      inflammatory processes. To assess the relevance of PTX3 in CSU patients and its
      association with CRP. METHODS: Plasma PTX3 and serum CRP concentrations were
      measured in patients with CSU of varying severity as well as in the healthy
      subjects. RESULTS: The concentrations of PTX3 and CRP were significantly
      increased in more severe CSU patients, when compared to mild CSU and the healthy
      controls. There was a significant correlation between concentrations of PTX3 and
      CRP. CONCLUSIONS: In contrast to CRP, PTX3 is produced at the sites of
      inflammation, therefore it seems that elevated PTX3 may result from activation of
      cells involved in local urticarial processes. Finally, the correlation between
      these two pentraxins suggests that they may be upregulated by the same mechanisms
      associated with acute phase response in CSU.

PMID- 25982554
TI  - Staphylococcus aureus induces IL-8 expression through its lipoproteins in the
      human intestinal epithelial cell, Caco-2.
AB  - Staphylococcus aureus can cause the intestinal inflammatory diseases. However,
      little is known about the molecular mechanism of S. aureus infection in the
      intestine. In the present study, we investigated whether S. aureus could
      stimulate human intestinal epithelial cells triggering inflammation. When the
      human intestinal epithelial cell-line, Caco-2, and the primary colon cells were
      stimulated with ethanol-inactivated S. aureus, IL-8 expression was induced in a
      dose-dependent manner. The inactivated S. aureus preferentially stimulated Toll
      like receptor (TLR) 2 rather than TLR4. Lipoproteins, lipoteichoic acid (LTA),
      and peptidoglycan (PGN) are considered as potential TLR2 ligands of S. aureus.
      Interestingly, S aureus lipoproteins and Pam2CSK4 mimicking Gram-positive
      bacterial lipoproteins, but not LTA and PGN of S. aureus, significantly induced
      IL-8 expression in Caco-2 cells. Furthermore, lipoprotein-deficient S. aureus
      mutant strain failed to induce IL-8 production. Collectively, these results
      suggest that S. aureus stimulates the human intestinal epithelial cells to induce
      the chemokine IL-8 production through its lipoproteins, potentially contributing
      the development of intestinal inflammation.

PMID- 25982555
TI  - Muscular interleukin-6 differentially regulates skeletal muscle adaptation to
      high-fat diet in a sex-dependent manner.
AB  - Interleukin-6 (IL-6) is now known to be not only a major cytokine controlling the
      immune system but also basic physiological variables such as body weight and
      metabolism. We recently reported that muscle-specific interleukin-6 deletion
      influences body weight and body fat in a sex-dependent manner in mice. When
      compared with littermate floxed controls, males gained less weight whereas
      females gained more weight after a 12-week high-fat diet treatment (HFD). We
      herewith report gender-differences of HFD treatment on fast and slow skeletal
      muscle in muscle-specific IL-6 deficient mice. While gross muscle architecture
      was normal, in males, HFD resulted in an increased proportion of medium-large
      size myofibers which was prevented by muscle IL-6 deletion. No modifications of
      fiber size were observed in females. HFD induced a fiber-type switching in
      tibialis muscle, increasing the proportion of fast-oxidative fibers and
      decreasing the fast-glycolytic fibers in female mice which were dependent on
      muscle IL-6. No changes of fiber types were detected in males. Finally, HFD was
      associated with increased collagen deposition in both sexes and muscle types.
      However, this effect was only associated to the presence of muscular IL-6 only on
      the slow soleus muscle in males. The results demonstrate sex-dependent effects of
      both HFD and muscle IL-6 deficiency in skeletal muscle. 

PMID- 25982556
TI  - Room temperature NO2 sensing: what advantage does the rGO-NiO nanocomposite have
      over pristine NiO?
AB  - In recent years, there has been increasing interest in synthesis of reduced
      graphene oxide (rGO)-metal oxide semiconductor (MOS) nanocomposites for room
      temperature gas sensing applications. Generally, the sensitivity of a MOS can be
      obviously enhanced by the incorporation of rGO. However, a lack of knowledge
      regarding how rGO can enhance gas-sensing performances of MOSs impedes its
      sensing applications. Herein, in order to get an insight into the sensing
      mechanism of rGO-MOS nanocomposites and further improve the sensing performances
      of NiO-based sensors at room temperature, an rGO-NiO nanocomposite was
      synthesized. Through a comparison study on room temperature NO2 sensing of rGO
      NiO and pristine NiO, an inverse gas-sensing behavior in different NO2
      concentration ranges was observed and the sensitivity of rGO-NiO was enhanced
      obviously in the high concentration range (7-60 ppm). Significantly, the
      stimulating effect of rGO on the recovery rate was confirmed by the sensing
      characteristics of rGO-NiO that was advantageous for the development of NO2
      sensors at room temperature. By comprehending the electronic interactions between
      the rGO-MOS nanocomposite and the target gas, this work may open up new
      possibilities for further improvement of graphene-based hybrid materials with
      even higher sensing performances. 

PMID- 25982558
TI  - Insights into the stimulatory mechanism of 2-aminoethoxydiphenyl borate on TREK-2
      potassium channel.
AB  - 2-Aminoethoxydiphenyl borate (2-APB) has been recently identified as a common
      agonist of TWIK-related K(+) channel (TREK)/TRAAK channels, a subfamily of two
      pore domain K(+) (K2P) channels. TREK-2 displays much higher sensitivity to 2-APB
      compared with TREK-1, despite that these two channels share the highest homology
      among K2P members. However, the structural basis for their difference in response
      to 2-APB still remains unknown. Here we identified that the cytosolic C-terminus
      (Ct) domain plays a dominant role in controlling the stimulatory effects of 2-APB
      on TREK-2 channel. The distal Ct region negatively regulates the effect of 2-APB,
      while the proximal Ct is sufficient to evoke the full 2-APB activation of the
      channel. Further mapping within the proximal Ct revealed that His368 is required
      for 2-APB activation, and the cooperation of the other non-conserved residues is
      also necessary. We also identified a secondary active site for 2-APB, which is
      located at the bottom of the transmembrane segment M2. Finally, we demonstrated
      that key residues or domains required for 2-APB activation are not involved in
      the gating mechanism of the selectivity filter. In summary, we reveal a unique
      modulatory model of TREK-2-Ct that distinguishes it from TREK-1 in high
      sensitivity to 2-APB. The cooperation of the non-conserved residues within the
      proximal Ct of TREK-2 plays a dominant role in the 2-APB-induced channel opening,
      whereas the distal Ct negatively regulates the process.

PMID- 25982557
TI  - Differential expression of CaMKII isoforms and overall kinase activity in rat
      dorsal root ganglia after injury.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) decodes neuronal activity
      by translating cytoplasmic Ca(2+) signals into kinase activity that regulates
      neuronal functions including excitability, gene expression, and synaptic
      transmission. Four genes lead to developmental and differential expression of
      CaMKII isoforms (alpha, beta, gamma, delta). We determined mRNA levels of these
      isoforms in the dorsal root ganglia (DRG) of adult rats with and without nerve
      injury in order to determine if differential expression of CaMKII isoforms may
      contribute to functional differences that follow injury. DRG neurons express mRNA
      for all four isoforms, and the relative abundance of CaMKII isoforms was
      gamma>alpha>beta=delta, based on the CT values. Following ligation of the 5th
      lumbar (L5) spinal nerve (SNL), the beta isoform did not change, but mRNA levels
      of both the gamma and alpha isoforms were reduced in the directly injured L5
      neurons, and the alpha isoform was reduced in L4 neurons, compared to their
      contemporary controls. In contrast, expression of the delta isoform mRNA
      increased in L5 neurons. CaMKII protein decreased following nerve injury in both
      L4 and L5 populations. Total CaMKII activity measured under saturating Ca(2+)/CaM
      conditions was decreased in both L4 and L5 populations, while autonomous CaMKII
      activity determined in the absence of Ca(2+) was selectively reduced in
      axotomized L5 neurons 21days after injury. Thus, loss of CaMKII signaling in
      sensory neurons after peripheral nerve injury may contribute to neuronal
      dysfunction and pain.

PMID- 25982559
TI  - Reduced severity of ischemic stroke and improvement of mitochondrial function
      after dietary treatment with the anaplerotic substance triheptanoin.
AB  - Triheptanoin, an oily substance, consists of glycerol bound to three molecules of
      heptanoic acid, a C7 odd-chain fatty acid. A triheptanoin-rich diet has
      anaplerotic effects because heptanoate metabolism yields succinate which delivers
      substrates to the Krebs cycle. While previous studies on the effects of
      triheptanoin focused on metabolic disorders and epilepsy, we investigated
      triheptanoin's effect on ischemic stroke. Mice were fed a triheptanoin-enriched
      diet for 14days; controls received soybean oil. Only mice fed triheptanoin had
      measurable quantities of odd-numbered fatty acids in the plasma and brain.
      Transient ischemia was induced in the brain by occlusion of the middle cerebral
      artery (MCAO) for 60min. One day later, mice were tested for neurological
      function (chimney, rotarod and corner tests) which was found to be better
      preserved in the triheptanoin group. Microdialysis demonstrated that the strong,
      neurotoxic increase of extracellular glutamate, which was observed in the mouse
      striatum during MCAO, was strongly reduced in triheptanoin-fed mice while glucose
      levels were not affected. Triheptanoin diet reduced the infarct area in stroked
      mice by about 40%. In ex vivo-experiments with isolated mitochondria, ischemia
      was found to cause a reduction of mitochondrial respiratory activity. This
      reduction was attenuated by triheptanoin diet in complex II and IV. In parallel
      measurements, ATP levels and mitochondrial membrane potential were reduced in
      control animals but were preserved in triheptanoin-fed mice. We conclude that
      triheptanoin-fed mice which sustained an experimental stroke had a significantly
      improved neurological outcome. This beneficial effect is apparently due to an
      improvement of mitochondrial function and preservation of the cellular energy
      state. Our findings identify triheptanoin as a promising new dietary agent for
      neuroprotection.

PMID- 25982560
TI  - Relationships between diet-related changes in the gut microbiome and cognitive
      flexibility.
AB  - Western diets are high in fat and sucrose and can influence behavior and gut
      microbiota. There is growing evidence that altering the microbiome can influence
      the brain and behavior. This study was designed to determine whether diet-induced
      changes in the gut microbiota could contribute to alterations in anxiety, memory
      or cognitive flexibility. Two-month-old, male C57BL/6 mice were randomly assigned
      high-fat (42% fat, 43% carbohydrate (CHO), high-sucrose (12% fat, 70% CHO
      (primarily sucrose) or normal chow (13% kcal fat, 62% CHO) diets. Fecal
      microbiome analysis, step-down latency, novel object and novel location tasks
      were performed prior to and 2weeks after diet change. Water maze testing for long
      and short-term memory and cognitive flexibility was conducted during weeks 5-6
      post-diet change. Some similarities in alterations in the microbiome were seen in
      both the high-fat and high-sucrose diets (e.g., increased Clostridiales), as
      compared to the normal diet, but the percentage decreases in Bacteroidales were
      greater in the high-sucrose diet mice. Lactobacillales was only significantly
      increased in the high-sucrose diet group and Erysipelotrichales was only
      significantly affected by the high-fat diet. The high-sucrose diet group was
      significantly impaired in early development of a spatial bias for long-term
      memory, short-term memory and reversal training, compared to mice on normal diet.
      An increased focus on the former platform position was seen in both high-sucrose
      and high-fat groups during the reversal probe trials. There was no significant
      effect of diet on step-down, exploration or novel recognitions. Higher
      percentages of Clostridiales and lower expression of Bacteroidales in high-energy
      diets were related to the poorer cognitive flexibility in the reversal trials.
      These results suggest that changes in the microbiome may contribute to cognitive
      changes associated with eating a Western diet.

PMID- 25982561
TI  - Neural correlates of audiovisual temporal processing--comparison of temporal
      order and simultaneity judgments.
AB  - Multisensory integration is one of the essential features of perception. Though
      the processing of spatial information is an important clue to understand its
      mechanisms, a complete knowledge cannot be achieved without taking into account
      the processing of temporal information. Simultaneity judgments (SJs) and temporal
      order judgments (TOJs) are the two most widely used procedures for explicit
      estimation of temporal relations between sensory stimuli. Behavioral studies
      suggest that both tasks recruit different sets of cognitive operations. On the
      other hand, empirical evidence related to their neuronal underpinnings is still
      scarce, especially with regard to multisensory stimulation. The aim of the
      current fMRI study was to explore neural correlates of both tasks using paradigm
      with audiovisual stimuli. Fifteen subjects performed TOJ and SJ tasks grouped in
      18-second blocks. Subjects were asked to estimate onset synchrony or temporal
      order of onsets of non-semantic auditory and visual stimuli. Common areas of
      activation elicited by both tasks were found in the bilateral fronto-parietal
      network, including regions whose activity can be also observed in tasks involving
      spatial selective attention. This can be regarded as an evidence for the
      hypothesis that tasks involving selection based on temporal information engage
      the similar regions as the attentional tasks based on spatial information. The
      direct contrast between the SJ task and the TOJ task did not reveal any regions
      showing stronger activity for SJ task than in TOJ task. The reverse contrast
      revealed a number of left hemisphere regions which were more active during the
      TOJ task than the SJ task. They were found in the prefrontal cortex, the parietal
      lobules (superior and inferior) and in the occipito-temporal regions. These
      results suggest that the TOJ task requires recruitment of additional cognitive
      operations in comparison to SJ task. They are probably associated with forming
      representations of stimuli as separate and temporally ordered sensory events.

PMID- 25982562
TI  - Contribution and interaction of kinin receptors and dynorphin A in a model of
      trigeminal neuropathic pain in mice.
AB  - Infraorbital nerve constriction (CION) causes hypersensitivity to facial
      mechanical, heat and cold stimulation in rats and mice and is a reliable model to
      study trigeminal neuropathic pain. In this model there is evidence that
      mechanisms operated by kinin B1 and B2 receptors contribute to heat hyperalgesia
      in both rats and mice. Herein we further explored this issue and assessed the
      role of kinin receptors in mechanical hyperalgesia after CION. Swiss and C57Bl/6
      mice that underwent CION or sham surgery or dynorphin A (1-17) administration
      were repeatedly submitted to application of either heat stimuli to the snout or
      mechanical stimuli to the forehead. Treatment of the animals on the fifth day
      after CION surgery with DALBK (B1 receptor antagonist) or HOE-140 (B2 receptor
      antagonist), both at 0.01-1MUmol/kg (i.p.), effectively reduced CION-induced
      mechanical hyperalgesia. Knockout mice for kinin B1, B2 or B1/B2 receptors did
      not develop heat or mechanical hyperalgesia in response to CION. Subarachnoid
      dynorphin A (1-17) delivery (15nmol/5MUL) also resulted in orofacial heat
      hyperalgesia, which was attenuated by post-treatment with DALBK (1 and 3MUmol/kg,
      i.p.), but was not affected by HOE-140. Additionally, treatment with an anti
      dynorphin A antiserum (200MUg/5MUL, s.a.) reduced CION-induced heat hyperalgesia
      for up to 2h. These results suggest that both kinin B1 and B2 receptors are
      relevant in orofacial sensory nociceptive changes induced by CION. Furthermore,
      they also indicate that dynorphin A could stimulate kinin receptors and this
      effect seems to contribute to the maintenance of trigeminal neuropathic pain.

PMID- 25982564
TI  - Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis.
AB  - Traumatic brain injury (TBI) is a major risk factor for dementia. Recently, TBI
      has also been suggested as a risk factor for frontotemporal dementia (FTD), and
      plasma immunoreactivity to the TAR-DNA binding protein 43 (TDP-43) has been
      observed in both patients with acute TBI and long-term survivors of this
      condition. We used a population-based study to estimate and compare the risk of
      FTD in individuals with and without TBI. Furthermore, we used a rat model of TBI
      to show that increased TDP-43 proteolysis following TBI produces FTD-like
      impairments, including abnormal limb-clasping, and impaired performances in the
      Morris water maze. We recruited 24,585 patients who received ambulatory or
      hospital care for TBI and 122,925 patients without TBI for this study. Each
      individual was investigated for 4years to evaluate FTD development, and data were
      analyzed by Cox proportional hazard regression. In the TBI rat model, behavior
      and TDP-43 inclusions were assessed following intracranial administration of a
      caspase-3 inhibitor or vehicle. FTD was more likely to occur in the TBI group
      than in the group without TBI (adjusted hazard ratio, 4.43; 95% confidence
      interval, 3.85-5.10; P<0.001). Rats developed behavioral impairments similar to
      those in patients with FTD after TBI. Further, the behavioral impairments were
      likely associated with TDP-43 short fragment mislocalization and accumulation.
      Our findings suggest that in humans, TBI is associated with a greater occurrence
      of FTD. Moreover, clinical FTD manifestations may be associated with TDP-43
      proteolysis, since impaired behaviors in TBI rats were reminiscent of those in
      humans with FTD.

PMID- 25982563
TI  - Sensory neuron subpopulation-specific dysregulation of intracellular calcium in a
      rat model of chemotherapy-induced peripheral neuropathy.
AB  - The purpose of the present study was to test the prediction that the unique
      manifestation of chemotherapeutic-induced peripheral neuropathy (CIPN) would be
      reflected in a specific pattern of changes in the regulation of the intracellular
      Ca(2+) concentration ([Ca(2+)]i) in subpopulations of cutaneous neurons. To test
      this prediction, we characterized the pattern of changes in mechanical
      nociceptive threshold associated with paclitaxel administration (2mg/kg, iv,
      every other day for four days), as well as the impact of target of innervation
      and paclitaxel treatment on the regulation of [Ca(2+)]i in subpopulations of
      putative nociceptive and non-nociceptive neurons. Neurons innervating the
      glabrous and hairy skin of the hindpaw as well as the thigh were identified with
      retrograde tracers, and fura-2 was used to assess changes in [Ca(2+)]i.
      Paclitaxel was associated with a persistent decrease in mechanical nociceptive
      threshold in response to stimuli applied to the glabrous skin of the hindpaw, but
      not the hairy skin of the hindpaw or the thigh. However, in both putative
      nociceptive and non-nociceptive neurons, resting [Ca(2+)]i was significantly
      lower in neurons innervating the thigh after treatment. The magnitude of the
      depolarization-evoked Ca(2+) transient was also lower in putative non-nociceptive
      thigh neurons. More interestingly, while paclitaxel had no detectable influence
      on either resting or depolarization-evoked Ca(2+) transients in putative non
      nociceptive neurons, in putative nociceptive neurons there was a subpopulation
      specific decrease in the duration of the evoked Ca(2+) transient that was largely
      restricted to neurons innervating the glabrous skin. These results suggest that
      peripheral nerve length alone, does not account for the selective distribution of
      CIPN symptoms. Rather, they suggest the symptoms of CIPN reflect an interaction
      between the toxic actions of the therapeutic and unique properties of the neurons
      deleteriously impacted.

PMID- 25982565
TI  - Predicting developmental outcomes in premature infants by term equivalent MRI:
      systematic review and meta-analysis.
AB  - BACKGROUND: This study aims to determine the prognostic accuracy of term MRI in
      very preterm born (<=32 weeks) or low-birth-weight (<=1500 g) infants for long
      term (>18 months) developmental outcomes. METHODS: We performed a systematic
      review searching Central, Medline, Embase, and PsycInfo. Two independent
      reviewers performed study selection, data extraction, and quality assessment. We
      documented sensitivity and specificity for three different MRI findings (white
      matter abnormalities (WMA), brain abnormality (BA), and diffuse excessive high
      signal intensity (DEHSI)), related to developmental outcomes including cerebral
      palsy (CP), visual and/or hearing problems, motor, neurocognitive, and behavioral
      function. Using bivariate meta-analysis, we estimated pooled sensitivity and
      specificity and plotted summary receiver operating characteristic (sROC) curves
      for different cut-offs of MRI. RESULTS: We included 20 papers published between
      2000 and 2013. Quality of included studies varied. Pooled sensitivity and
      specificity values (95 % confidence interval (CI)) for prediction of CP combining
      the three different MRI findings (using normal/mild vs. moderate/severe cut-off)
      were 77 % (53 to 91 %) and 79 % (51 to 93 %), respectively. For prediction of
      motor function, the values were 72 % (52 to 86 %) and 62 % (29 to 87 %),
      respectively. Prognostic accuracy for visual and/or hearing problems,
      neurocognitive, and/or behavioral function was poor. sROC curves of the
      individual MRI findings showed that presence of WMA provided the best prognostic
      accuracy whereas DEHSI did not show any potential prognostic accuracy.
      CONCLUSIONS: This study shows that presence of moderate/severe WMA on MRI around
      term equivalent age can predict CP and motor function in very preterm or low
      birth-weight infants with moderate sensitivity and specificity. Its ability to
      predict other long-term outcomes such as neurocognitive and behavioral
      impairments is limited. Also, other white matter related tests as BA and DEHSI
      demonstrated limited prognostic value. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42013006362.

PMID- 25982566
TI  - Increased risk of pneumonia associated with angiotensin-converting enzyme (CD143)
      rs4340 polymorphism.
AB  - The study aims to investigate the genetic association between rs4340 polymorphism
      at intron 16 of the angiotensin-converting enzyme (CD143) gene and pneumonia
      predisposition. Electronic database of PubMed, Embase, and CNKI (China National
      Knowledge Infrastructure) was searched for the studies addressing the association
      between CD143 rs4340 genotypes and pneumonia risk. The odds ratio (OR) with its
      95 % confidence interval (CI) was employed to estimate the association. In total,
      ten case-control studies, including 1239 pneumonia cases and 2400 healthy
      controls, met the inclusion criteria. Our results showed a significant
      association between rs4340 SNP and pneumonia risk using the recessive model (OR
      1.43, 95 % CI 1.20-1.70). A significantly increased risk was also indicated under
      the recessive model in Asian populations (OR 1.63, 95 % CI 1.16-2.30), Caucasian
      populations (OR 1.34, 95 % CI 1.09-1.65), community-acquired pneumonia (OR 1.42,
      95 % CI 1.16-1.75) rather than nosocomial pneumonia (OR 1.47, 95 % CI 0.97-2.23).
      However, further studies with gene-gene and gene-environmental interactions
      should be considered to confirm this association. 

PMID- 25982567
TI  - Oxidative stress levels are correlated with P15 and P16 gene promoter methylation
      in myelodysplastic syndrome patients.
AB  - Oxidative stress and abnormal DNA methylation have been implicated in some types
      of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are
      observed in MDS patients, we analyzed the correlation of intracellular levels of
      peroxides, superoxide anion, and glutathione (GSH), as well as ratios of
      peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene
      promoters in bone marrow leukocytes from MDS patients. Compared to controls,
      these patients had lower GSH content, higher peroxide levels, peroxides/GSH and
      superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16
      gene promoters. Moreover, patients with methylated P15 gene had higher oxidative
      stress levels than patients without methylation (peroxides: 460 +/- 42 MIF vs 229
      +/- 25 MIF, p = 0.001; superoxide: 383 +/- 48 MIF vs 243 +/- 17 MIF, p = 0.022;
      peroxides/GSH: 2.50 +/- 0.08 vs 1.04 +/- 0.34, p < 0.001; superoxide/GSH: 1.76 +/
      0.21 vs 1.31 +/- 0.10, p = 0.007). Patients with methylated P16 and at least one
      methylated gene had higher peroxide levels as well as peroxides/GSH ratio than
      patients without methylation. Interestingly, oxidative stress levels allow the
      discrimination of patients without methylation from ones with methylated P15,
      methylated P16, or at least one methylated (P15 or P16) promoter. Taken together,
      these findings support the hypothesis that oxidative stress is correlated with
      P15 and P16 hypermethylation. 

PMID- 25982568
TI  - Chronotherapeutic treatments for depression in youth.
AB  - Chronotherapeutics such as wake therapy and bright light therapy are well
      established methods in treating adults with depressive disorders and are
      additionally beneficent for sleep regulation. Few studies concerning
      chronotherapeutics in juvenile depression exist, though the established
      treatments are insufficient and sleep disorders often co-occur. In this study, we
      investigate the impact of two types of chronotherapeutics on depressive symptoms
      and sleep behavior in a juvenile setting. Juvenile inpatients (n = 62) with
      moderate to severe depressive symptoms took part in either a combined setting
      consisting of one night wake therapy followed by 2 weeks bright light therapy or
      in a setting of bright light therapy alone. Depressive symptoms, general
      psychopathology, clinical impression and sleep behavior were measured before
      (T1), directly after (T2) and 2 weeks after intervention (T3). Depressive
      symptoms decreased while sleep quality increased in both groups. The bright light
      therapy alone group showed further improvement at T3 in regards to depressive
      symptoms. Correlation analyses indicated significant negative correlations
      between sleep quality and awaking after restorative sleep with the depressive
      symptoms. However, only awaking after restorative sleep had a predictive impact
      on treatment outcome. The present study provides first evidence for a positive
      impact of chronotherapeutic interventions on treatment outcome in depressed
      juvenile inpatients. Bright light therapy seems to stabilize and further enhance
      reduction of depressive symptoms during follow-up, whereas one night wake therapy
      does not have an additional long-lasting impact on depressive symptoms and sleep
      parameters.

PMID- 25982569
TI  - Biomphalaria straminea (Mollusca: Planorbidae) as an intermediate host of
      Drepanocephalus spp. (Trematoda: Echinostomatidae) in Brazil: a morphological and
      molecular study.
AB  - Species of trematodes belonging to the genus Drepanocephalus are intestinal
      parasites of piscivorous birds, primarily cormorants (Phalachrocorax spp.), and
      are widely reported in the Americas. During a 4-year malacological study
      conducted on an urban lake in Brazil, 27-collar-spined echinostome cercariae were
      found in 1665/15,459 (10.7 %) specimens of Biomphalaria straminea collected. The
      cercariae were identified as Drepanocephalus spp. by sequencing the 18S (SSU)
      rDNA, ITS1/5.8S rDNA/ITS2 (ITS), 28S (LSU) rDNA region, cytochrome oxidase
      subunit 1 (CO1), and nicotinamide adenine dinucleotide dehydrogenase subunit 1
      (ND1) markers. In experimental life cycle studies, metacercariae developed in
      laboratory-reared guppies (Poecilia reticulata); however, attempts to infect
      birds and rodents were unsuccessful. Two closely related morphotypes of cercariae
      were characterized. One species, identified by molecular markers as a genetic
      variant of Drepanocephalus auritus (99.9 % similarity at SSU, ITS, LSU; 97.2 % at
      CO1; 95.8 % at ND1), differs slightly from an archived North American isolate of
      this species also sequenced as part of this study. A second species, putatively
      identified as Drepanocephalus sp., has smaller cercariae and demonstrates
      significant differences from D. auritus at the CO1 (11.0 %) and ND1 (13.6 %)
      markers. Aspects related to the morphological taxonomic identification of 27
      collar-spined echinostome metacercariae are briefly discussed. This is the first
      report of the involvement of molluscs of the genus Biomphalaria in the
      transmission of Drepanocephalus and the first report of D. auritus in South
      America.

PMID- 25982570
TI  - Cytokine signature and antibody-mediated response against fresh and attenuated
      Anisakis simplex (L3) administration into Wistar rats: implication for anti
      allergic reaction.
AB  - The third larval stage (L3) of Anisakis simplex (Anisakidae) is one of the
      zoonotic parasitic nematodes in the musculature and visceral organs of marine
      fishes belonging to family Moronidae. The consumption of these high-commercial
      value fish is widespread in many countries around the Mediterranean Sea including
      Egypt. The presence of these larvae in fish muscles poses a potential consumer
      hazard due to the parasite's ability to cause anisakidosis. Forty-two out of 60
      (70%) of the European seabass Dicentrarchus labrax were found to be naturally
      infected by L3 of A. simplex in the form of encapsulated juveniles in the fish
      musculature. Morphological examination of recovered parasites by light and
      scanning electron microscopy showed that, in general, all specimens examined
      closely resembled A. simplex (L3). To evaluate the allergenicity of this
      nematode, white blood cell count; levels of T helper 1 (Th1) [interferon (IFN)
      gamma and tumor necrosis factor (TNF)-alpha)], Th2 [IL-4, IL-5, and IL-6], and
      Th17 [IL-17] related cytokines; total IgE and IgG antibodies; and nitric oxide
      (NO) were measured in the plasma of Wistar rats sensitized by oral inoculation
      with fresh, frozen, and heat-treated A. simplex L3 or rats intraperitoneally
      injected with L3 crude extract. Rats sensitized with fresh and frozen L3 larvae
      produced significantly higher levels of IFN-gamma, IL-5, IL-17, and total IgE as
      compared to control rats. Heat-treated larvae administration resulted in a
      significant rise of IFN-gamma, TNF-alpha, IL-5, and total IgE in comparison to
      control rats. Intraperitoneal sensitizations enhanced release of IFN-gamma, TNF
      alpha, and total IgE. Oral sensitization led to a significant production of NO.
      Thereby, frozen or cooked larval L3 cannot inhibit the release of Th-related
      cytokines and IgE, which might impact on the overall anti-parasitic immunity.

PMID- 25982571
TI  - Factors that influence the shedding of Blastocystis cysts in an irritable bowel
      syndrome (IBS) patient--an evidence-based case study.
AB  - Blastocystis is one of the most common gut parasites found in the intestinal
      tract of humans and animals. We have previously reported the irregular shedding
      of Blastocystis cysts in stools from infected patients. In the present study, we
      assess the factors influencing shedding patterns from a Blastocystis ST3-infected
      IBS patient. The stools samples were voluntarily submitted for examination for a
      period of 30 days from Blastocystis ST3-infected IBS patient. A questionnaire on
      the factors that could influence the shedding pattern of the cysts was designed
      to assess the following information: (a) the frequency of frequenting the toilet
      in a day, (b) the timing of frequenting the toilet, (c) the stool forms, (d) the
      type of mood the patient was in when frequenting the toilet and (e) food intake.
      A total of 79 stool samples were collected for 30 days. The highest number of
      cysts recorded when the patient visited the toilet three times a day was 22.2 *
      10(6) cysts/g. Frequenting the toilet between 6 a.m. to 11.59 a.m. showed the
      highest number of cysts, i.e. 21.7 * 10(6) cysts/g. Semi-solid forms showed the
      highest cyst count, i.e. 2.00 * 10(6) cysts/g. Irregular shedding of cysts was
      seen in 10 out of 30 days where the widest range recorded on day 17 was between 0
      to 1.2 * 10(6) cysts/g. The average daily cyst count on days of emotional
      fluctuations was from 0 to 5.13 * 10(6) cysts/g. In conclusion, the study
      confirms that there are factors influencing shedding patterns of Blastocystis,
      and these have important implications when it comes to diagnosis and transmission
      of the parasite.

PMID- 25982573
TI  - Destructive effect of gamma irradiation on Echinococcus granulosus metacestodes.
AB  - Current options for treatment of cystic echinococcosis (CE), including
      chemotherapeutics and surgical approaches, are not satisfactory in certain cases
      of resistant cysts in vulnerable or inaccessible organs. Therefore, potential
      means of therapy are needed. The present work evaluated the effect of gamma
      irradiation on mestacestode causing CE. Metacestode of Echinococcus granulosus
      were exposed to 15, 30, and 60 Gy irradiation and examined after 24 h for
      viability, morphologic, and ultrastuctural alterations by light and electron
      microscopy. Apoptosis was determined by caspase-3 activity by colorimetric assay
      and immunohistochemistry. The irradiated metacestodes showed loss of viability,
      damage of protoscolices, formation of lipid droplets and vacuoles, and separation
      of the germinal layer. Apoptosis was prominent after irradiation. Our results
      suggested that gamma irradiation have therapeutic potential in CE. Moreover,
      understanding the destructive effect of irradiation may help in developing
      prophylactic measures against CE. Further studies are needed to test the efficacy
      of ionizing radiation in long-term animal models.

PMID- 25982572
TI  - Suitable in vitro culture of Eimeria bovis meront II stages in bovine colonic
      epithelial cells and parasite-induced upregulation of CXCL10 and GM-CSF gene
      transcription.
AB  - We here established a suitable in vitro cell culture system based on bovine
      colonic epithelial cells (BCEC) for the development of Eimeria bovis merozoites I
      and the characterization of early parasite-induced innate epithelial host cell
      reactions as gene transcription of proinflammatory molecules. Both primary and
      permanent BCEC (BCEC (rim) and BCEC(perm)) were suitable for E. bovis merozoite I
      invasion and subsequent development of meronts II leading to the release of
      viable merozoites II. E. bovis merozoite II failed to develop any further neither
      into gamont nor oocyst stages in BCEC in vitro. E. bovis merozoite I induced
      innate epithelial host cell reactions at the level of CXC/CCL chemokines (CXCL1,
      CXCL8, CXCL10, CCL2), IL-6, and GM-CSF gene transcription. Overall, both BCEC
      types were activated by merozoite I infections since they showed significantly
      enhanced gene transcript levels of the immunomodulatory molecules CXCL10 and GM
      CSF. However, gene transcription profiles of BCEC(prim) and BCEC(perm) revealed
      different reaction patterns in response to merozoite I infection with regard to
      quality and kinetics of chemokine/cytokine gene transcription. Although both BCEC
      types equally showed most prominent responses for CXCL10 and GM-CSF, the
      induction of CXCL1, CXCL8, CCL2, and IL-6 gene transcripts varied qualitatively
      and quantitatively. Our results demonstrate that BCEC seem capable to respond to
      E. bovis merozoite I infection by the upregulation of CXCL10 and GM-CSF gene
      transcription and therefore probably contribute to host innate effector
      mechanisms against E. bovis.

PMID- 25982574
TI  - New records of species of Philometra (Nematoda: Philometridae) from marine fishes
      off New Caledonia, including P. cephalopholidis sp. n. from Cephalopholis
      sonnerati (Serranidae).
AB  - Two different species of Philometra Costa, 1845 were collected from marine
      perciform fishes, the tomato hind Cephalopholis sonnerati (Valenciennes)
      (Serranidae) and the painted sweetlips Diagramma pictum (Thunberg) (Haemulidae),
      from off New Caledonia, South Pacific. Nematodes (only males) from the gonad of
      C. sonnerati represent a new taxon, P. cephalopholidis sp. n., which is mainly
      characterized by almost equally long spicules (length 186-228 MUm), the shape and
      structure of the gubernaculum with a dorsally lamellate distal tip, and the
      structure of the caudal end. The nematodes (only gravid females) from abdominal
      tissues of D. pictum may represent an undescribed species, but, because of the
      absence of conspecific males, they could not be specifically identified.
      Philometra cephalopholidis is the sixth nominal species of this genus recorded
      from fishes off New Caledonia and the thirteenth species of these parasites
      described from fishes of the family Serranidae.

PMID- 25982575
TI  - Amelioration of some immunological disorders caused by the faeces of the dominant
      true house dust mites in El-Minia Governorate, Egypt.
AB  - BACKGROUND: House dust mites (HDMs) faeces are the main factor involved in
      respiratory disorder. The true HDMs, Dermatophagoides pteronyssinus and D.
      farinae, detected in the samples collected from the house dust are the most
      important causes of allergic disorders such as asthma. OBJECTIVE: The aim of this
      investigation was to study the curcuma and karkade amelioration of the allergenic
      immunological disorder, especially some cytokines, IgE and ROS, caused by the
      faeces of the dominant true HDM, D. pteronyssinus and D. farinae in valley and
      desert houses in EL-Minia Governorate, respectively. METHODS: HDM cultures,
      faeces isolation, plant extraction and ELISA techniques were used. Male albino
      rats were classified into control, inhaled, and treated groups. RESULTS: The
      present immunological study on the dominant allergenic true HDMs, D.
      pteronyssinus and D. farinae, revealed that significantly higher serum levels of
      TNF-alpha, IL-1beta, IL-4, IL-13 and IgE were found in rats treated with both D.
      pteronyssinus and D. farinae faeces than the other groups. In addition,
      statistical analysis of ROS data showed significant difference between the
      curcuma- and karkade-treated groups and either the control or the faeces-treated
      groups (P<0.05). CONCLUSIONS: Some immunological disturbances caused by repeated
      exposure to the faeces of two dominant allergenic true HDM species (D.
      pteronyssinus and D. farinae) in the valley and desert houses could be
      ameliorated by curcuma and karkade.

PMID- 25982576
TI  - Study of SH2D1A gene mutation in paediatric patients with B-cell lymphoma.
AB  - BACKGROUND: X-linked lymphoproliferative disease (XLP) is an often fatal
      inherited immunodeficiency disorder characterised by fulminant infectious
      mononucleosis, acquired haemophagocytic lymphohistiocytosis,
      dysgammaglobulinaemia and malignant lymphoma. Given the paucity of data on the
      genetic stratification of XLP gene mutations in paediatric patients diagnosed
      with B-cell lymphoma, we sought to determine the existence of such association in
      the present study. METHODS: We studied 20 male subjects diagnosed with non
      Hodgkin B-cell lymphoma. RESULTS: Eleven patients had laboratory evidence of EBV
      infection by serology and quantitative PCR. The SH2D1A gene analysis was negative
      in all patients. CONCLUSIONS: This is the first study to analyse the SH2D1A gene
      mutations in Iranian paediatric patients diagnosed with lymphoma. Although we
      could not demonstrate such an association in our cohort of patients, larger,
      multi-centre studies are required to extend and confirm our early findings.

PMID- 25982577
TI  - Exposure to pets and risk of sensitisation to house dust mite, cat and dog
      allergens in a pre-school children population of an Andalusian seaside town.

PMID- 25982578
TI  - Analysis of FOXP3 gene in children with allergy and autoimmune diseases.
AB  - BACKGROUND: Allergy and autoimmunity are important immunological entities
      underlying chronic diseases in children. In some cases both entities develop
      simultaneously in the same patient. FOXP3 gene codes for a transcription factor
      involved in regulation of the immune system. Considering that regulatory T cells
      are involved in controlling immunological disease development, and the relevant
      role of FOXP3 in this kind of T cells, the objective of this study was to analyse
      the FOXP3 gene in the most prevalent autoimmune diseases and/or allergies in
      childhood in a European population. METHODS: A total of 255 Caucasian
      individuals, 95 controls and 160 patients diagnosed with allergic, autoimmune or
      both diseases were included in this study. The molecular analysis of FOXP3 was
      performed by DNA sequencing following the recommendations for quality of the
      European Molecular Genetics Quality Network. Genomic DNA was extracted from
      peripheral blood of all participants and was amplified using the polymerase chain
      reaction. After the visualisation of the amplified fragments by agarose gel
      electrophoresis, they were sequenced. RESULTS: Thirteen different polymorphisms
      in FOXP3 gene were found, seven of which had not been previously described. The
      mutated allele of SNP 7340C>T was observed more frequently in the group of male
      children suffering from both allergic and autoimmune diseases simultaneously
      (p=0.004, OR=16.2 [1.34-195.15]). CONCLUSIONS: In this study we identified for
      first time genetic variants of FOXP3 that are significantly more frequent in
      children who share allergic and autoimmune diseases. These variants mainly affect
      regulatory sequences that could alter the expression levels of FOXP3 modifying
      its function including its role in Treg cells.

PMID- 25982579
TI  - Urinary leukotriene and Bcl I polymorphism of glucocorticoid receptor gene in
      preschoolers with recurrent wheezing and high risk of asthma.
AB  - BACKGROUND: Urinary leukotriene (LTE4) is an important marker of airway
      inflammation presence. A relationship between single nucleotide polymorphism in
      the glucocorticoid receptor (GCR) gene promoter (Bcl I polymorphism), development
      of asthma and sensitivity to glucocorticoids has been hypothesised. OBJECTIVE: To
      explore the possible association between the Bcl I polymorphism and baseline
      levels of urinary LTE4 in preschoolers with recurrent wheezing episodes. We
      prospectively enrolled and classified 86 preschoolers based on the risk of
      developing asthma (by the Asthma Predictive Index [API]). METHODS: At admission
      standardised questionnaires for demographics and respiratory illness
      characteristics were completed. The Bcl I polymorphism of the GCR was determined
      by a PCR-RFLP assay from blood samples, and urinary leukotriene was assessed from
      urine samples by an enzyme immunoassay. RESULTS: We enrolled 86 preschoolers (46
      with positive API and 40 with negative API). There were no statistical
      differences in demographic, respiratory illnesses and wheezing episodes
      characteristics between both groups. Also, the prevalence of Bcl I polymorphism
      was similar between positive vs. negative API groups (34.8% vs. 38.9% for
      homozygote GG, 56.5% vs. 52.8% for heterozygote GC, 8.7% vs. 8.3% for homozygote
      CC, respectively, p=0.94). However, urinary LTE4 (median [IQR]) was higher in
      preschoolers with positive than negative API (7.18 [5.57-8.96pg/ml] vs. 6.42
      [3.96-8.07pg/ml], p=0.02, respectively). CONCLUSIONS: In our population, wheezing
      preschoolers with positive API exhibit higher levels of urinary LTE4 than those
      with negative API; but there were no differences in Bcl I polymorphism of the
      GCR.

PMID- 25982580
TI  - Diamine oxidase levels in different chronic urticaria phenotypes.
AB  - BACKGROUND: Diamine oxidase (DAO) is a polyamine-degrading enzyme also implicated
      in histamine metabolism. Chronic urticaria (CU) has a wide spectrum of clinical
      presentations and causes. Anisakis sensitisation associated chronic urticaria
      (CU+) has been characterised as a phenotype with different clinical and
      immunological characteristics and possibly associated with previous acute
      parasitism. We aimed to analyse serum DAO levels in different CU phenotypes. We
      further analysed the possible association of DAO with fish eating habits.
      METHODS: We studied 35 CU+ patients and 39 non-sensitised CU patients (CU-) as
      well as 19 controls. We analysed fish-eating frequency as well as fish intake
      associated exacerbation of CU (FIAE) or gastro-intestinal complaints (GI). DAO
      levels were further analysed with respect to lymphoproliferative responses,
      cytokine and specific IgE production. RESULTS: DAO levels were not different
      between CU and controls, but were significantly higher in CU+ than in CU-. CU+
      patients with FIAE had lower DAO levels, but no differences were detected in
      patients with GI. DAO levels correlated positively with oily and canned fish
      consumption in CU-. In CU+, DAO levels correlated positively with specific
      Anisakis IgE, percentages of proliferation in Anisakis stimulated peripheral
      blood lymphocytes, serum IL-2 and IL-6, but correlated negatively with mitogen
      stimulated TGF-beta in supernatants. CONCLUSIONS: DAO levels in CU depend on fish
      eating habits and in CU+ on the amount of specific IgE production. In the CU+
      phenotype, lower levels of DAO predispose to urticaria exacerbation after fish
      intake, probably due to a relative insufficient enteric availability of this
      enzyme.

PMID- 25982581
TI  - Molecular-based diagnosis of respiratory allergic diseases in children from
      Curitiba, a city in Southern Brazil.
AB  - BACKGROUND: Prevalence of respiratory allergic diseases has increased worldwide.
      Identification of the aeroallergens involved in allergenic sensitisation is
      important for diagnosis, treatment and prevention. OBJECTIVE: To verify the
      molecular pattern of sensitisation to aeroallergens in patients with allergic
      respiratory diseases using microarray technique for specific IgE antibody
      detection. METHODS: Cross-sectional study of 101 children with allergic rhinitis
      was followed in an outpatient clinic. All patients had positive skin prick tests
      (SPT) to at least one of the following antigens: Dermatophagoides pteronyssinus,
      Blomia tropicalis, Blattella germanica, Lolium multiflorum, and dog and cat
      epithelium. Serum specific IgE antibodies (sIgE) to mites, animal epithelia,
      fungi, cockroach and pollens components were determined by ImmunoCAP ISAC.
      RESULTS: sIgE to group 1 and 2 mite allergens showed higher positive rates: Der p
      1 (74.2%), Der p 2 (73.3%), Der f 1 (74.2%), Der f 2 (72.3%). sIgE to animal
      epithelia were less frequent, Can f 1, Can f 2, Can f 3 in 4.9%, 2.9%, 1.9%
      respectively and Fel d 1, Fel d 2, Fel d 4 in 16.8%, 0.9% and 1.9%. respectively.
      Sensitisation to fungi and cockroach were rare, except for Bla g 7, to which
      16.8% were positive. There was no significant recognition for tree pollens group.
      For grass, sIgE were detected to Cyn d 1 in 16.8%, Phl p 1 and Phl p 4 in 14.8%
      and 12.9%, respectively. CONCLUSION: Knowing that the pattern of allergic
      sensitisation varies according to environment and population, our results
      reinforce the need for local studies, using molecular-based diagnosis.

PMID- 25982582
TI  - Management of clinical stage I testicular seminoma: active surveillance versus
      adjuvant chemotherapy.
AB  - PURPOSE: Surveillance after orchiectomy alone has become popular in the
      management of clinical stage I nonseminomatous germ cell testicular tumors (CSI
      NSGCTT), and adjuvant chemotherapy has been accepted in high-risk CSI NSGCTT.
      Because of the late toxicity of standard radiotherapy in CSI testicular seminoma
      (SGCTT), this therapeutic approach has been accepted also in the management of
      CSI SGCTT. In the current study, we analyzed single-center experience with risk
      adapted therapeutic approaches (active surveillance and adjuvant chemotherapy) in
      patients with CSI SGCTT. PATIENTS AND METHODS: The study analyzed a total of 90
      patients collected at a single center from April 2008 to March 2015 with CSI
      SGCTT who were stratified into two groups according to risk-adapted therapeutic
      approaches. RESULTS: In the group A (low-risk CSI SGCTT-no rete testis invasion,
      tumor size <4 cm, pT1 stage), which consisted of 74 patients who underwent
      surveillance, relapse occurred in seven (9.5 %) patients after a mean follow-up
      of 14.5 months. In the group B (high-risk CSI SGCTT-rete testis invasion, tumor
      size >4 cm or pT >= 2 stage), which consisted of 16 patients who were treated
      with adjuvant chemotherapy, relapse occurred in two (12.5 %) patients after a
      mean follow-up of 13.8 months. Overall survival of patients in both groups was
      100 %. The statistically significant difference in progression-free survival
      between these two groups was not found. CONCLUSIONS: Radiotherapy is currently
      not recommended as an adjuvant treatment in CSI SGCTT patients. The benefit of
      using risk-adapted therapeutic approaches in CSI SGCTTs patients is evident.

PMID- 25982583
TI  - The effect of lanthanum carbonate on metabolic acidosis in patients with chronic
      kidney disease stage IV, V and V-D.
AB  - PURPOSE: Hyperphosphatemia and metabolic acidosis are frequently encountered in
      advanced chronic kidney disease (CKD) patients. Correction of metabolic acidosis
      in patients with advanced CKD leads to a decrease in the progression of renal
      impairment and improves nutritional outcomes. Lanthanum carbonate is used for
      control of hyperphosphatemia. This study evaluated the effect of lanthanum
      carbonate on metabolic acidosis in CKD IV-V patients and in patients on dialysis.
      METHODS: Retrospective data of patients in whom lanthanum carbonate therapy was
      initiated were collected from 2009 to 2013 in a single dialysis center. Of the 79
      patients in whom lanthanum carbonate was introduced, 51 patients were included in
      the analysis. Of the 51 patients, 39 patients received chronic hemodialysis, two
      patients received peritoneal dialysis therapy, and 10 patients had stage IV-V CKD
      not on dialysis. The primary outcome was the serum bicarbonate change after the
      introduction of lanthanum carbonate. RESULTS: There was a significant increase in
      mean serum bicarbonate concentration of 2.79 mmol/L (p <= 0.001) compared to
      baseline. The increase remained in the CKD IV-V patients (2.50 mmol/L, p = 0.005)
      and in the patients on dialysis (2.81 mmol/L, p < 0.001). Serum bicarbonate
      remained higher (p > 0.05) than baseline up to 6 months after lanthanum carbonate
      introduction. CONCLUSION: In this study, lanthanum carbonate introduction
      increased serum bicarbonate concentration in a small sample of CKD IV-V patients
      and in patients on dialysis. Further studies are needed to confirm this effect
      and investigate whether the correction of metabolic acidosis by using lanthanum
      carbonate in CKD IV-V patients can improve clinical outcomes.

PMID- 25982584
TI  - Continence Index: a new screening questionnaire to predict the probability of
      future incontinence in older women in the community.
AB  - PURPOSE: Urinary incontinence (UI) is a chronic, costly condition that impairs
      quality of life. To identify older women most at risk, the Medical Epidemiologic
      and Social Aspects of Aging (MESA) datasets were mined to create a set of
      questions that can reliably predict future UI. METHODS: MESA data were collected
      during four household interviews at approximately 1 year intervals. Factors
      associated with becoming incontinent at the second interview (HH2) were
      identified using logistic regression (construction datasets). Based on p values
      and odds ratios, eight potential predictive factors with their 256 combinations
      and corresponding prediction probabilities formed the Continence Index. Its
      predictive and discriminatory capability was tested against the same cohort's
      outcome in the fourth survey (HH4 validation datasets). Sensitivity analysis,
      area under receiver operating characteristic (ROC) curve, predicted probabilities
      and confidence intervals were used to statistically validate the Continence
      Index. RESULTS: Body mass index, sneezing, post-partum UI, urinary frequency,
      mild UI, belief of developing UI in the future, difficulty stopping urinary
      stream and remembering names emerged as the strongest predictors of UI. The
      confidence intervals for prediction probabilities strongly agreed between
      construction and validation datasets. Calculated sensitivity, specificity, false
      positive and false-negative values revealed that the areas under the ROCs (0.802
      and 0.799) for the construction and validation datasets, respectively, indicated
      good discriminatory capabilities of the index as a predictor. CONCLUSION: The
      Continence Index will help identify older women most at risk of UI in order to
      apply targeted prevention strategies in women that are most likely to benefit.

PMID- 25982585
TI  - Hypofractionated radiation therapy for treatment of bladder carcinoma in patients
      aged 90 years and more: A new paradigm to be explored?
AB  - INTRODUCTION: There are only scarce data on the optimal management of patients
      who present with a bladder carcinoma and who are aged 90 years and older.
      PATIENTS AND METHODS: We retrospectively reviewed records from radiotherapy
      departments from two university hospitals, two private centers and one public
      center to identify patients who underwent radiotherapy for bladder cancer over
      the past decade and who were aged 90 years or older. From 2003 to 2013, 14
      patients aged 90 years or older receiving RT for bladder malignant tumors were
      identified. RESULTS: Mean age was 92.7 years. Ten patients (71 %) had a general
      health status altered (PS 2-3) at the beginning of RT. A total of 14 RT courses
      were delivered, including six treatments (43 %) with curative intent and eight
      treatments (57 %) with palliative intent. Palliative intent mainly encompassed
      hemostatic RT (36 %). At last follow-up, two patients (14 %) experienced complete
      response, one patient (7 %) experienced partial response, three patients (21 %)
      had their disease stable, and three patients (21 %) experienced tumor
      progression, of whom two patients with the progression of symptoms. There was no
      reported high-grade acute local toxicity in 14 patients (100 %). One patient
      experienced delayed grade 2 toxicity with pain and lower urinary tract symptoms.
      At last follow-up, seven patients (50 %) were deceased. Cancer was the cause of
      death for five patients. CONCLUSION: Hypofractionated radiotherapy remains
      feasible for nonagenarians with bladder cancer. Further investigations including
      analysis of geriatric comorbidities and impact of treatments on quality of life
      should be conducted.

PMID- 25982587
TI  - Liver disease in pregnancy.
AB  - Liver disease in pregnancy, either pre-existing or pregnancy specific, can be
      associated with a significant risk of maternal and fetal morbidity and mortality.
      Here, we review the presentation, management and perinatal outcomes of common
      causes of liver disease. 

PMID- 25982588
TI  - Uterine Transplantation: Ethical Considerations within Middle Eastern
      Perspectives.
AB  - The field of reproductive medicine witnessed a breakthrough in September 2014
      with the first successful live birth post uterine transplantation. This success
      represents the culmination of decades' worth of research on infertility and
      reproductive medicine. This subject of infertility gathers special attention in
      the Middle East, as childbearing is given paramount importance in the family
      unit. And as with any new medical advancement, Middle Eastern people look to
      their religious authorities for guidance. This paper describes the various
      ethical quandaries related to uterine transplantation, from a perspective of the
      religious and societal factors that are unique to the Middle East, and embeds
      them within the conversation of its alternative solutions.

PMID- 25982586
TI  - Identification and analysis of novel salt responsive candidate gene based SSRs
      (cgSSRs) from rice (Oryza sativa L.).
AB  - BACKGROUND: Majority of the Asian people depend on rice for nutritional energy.
      Rice cultivation and yield are severely affected by soil salinity stress
      worldwide. Marker assisted breeding is a rapid and efficient way to develop
      improved variety for salinity stress tolerance. Genomic microsatellite markers
      are an elite group of markers, but there is possible uncertainty of linkage with
      the important genes. In contrast, there are better possibilities of linkage
      detection with important genes if SSRs are developed from candidate genes. To the
      best of our knowledge, there is no such report on SSR markers development from
      candidate gene sequences in rice. So the present study was aimed to identify and
      analyse SSRs from salt responsive candidate genes of rice. RESULTS: In the
      present study, based on the comprehensive literature survey, we selected 220
      different salt responsive genes of rice. Out of them, 106 genes were found to
      contain 180 microsatellite loci with, tri-nucleotide motifs (56%) being most
      abundant, followed by di-(41%) and tetra nucleotide (2.8%) motifs. Maximum loci
      were found in the coding sequences (37.2%), followed by in 5'UTR (26%), intron
      (21.6%) and 3'UTR (15%). For validation, 19 primer sets were evaluated to detect
      polymorphism in diversity analysis among the two panels consisting of 17 salt
      tolerant and 17 susceptible rice genotypes. Except one, all primer sets exhibited
      polymorphic nature with an average of 21.8 alleles/primer and with a mean PIC
      value of 0.28. Calculated genetic similarity among genotypes was ranged from 19%
      89%. The generated dendrogram showed 3 clusters of which one contained entire 17
      susceptible genotypes and another two clusters contained all tolerant genotypes.
      CONCLUSION: The present study represents the potential of salt responsive
      candidate gene based SSR (cgSSR) markers to be utilized as novel and remarkable
      candidate for diversity analysis among rice genotypes differing in salinity
      response.

PMID- 25982589
TI  - C-5 Propynyl Modifications Enhance the Mechanical Stability of DNA.
AB  - Increased thermal or mechanical stability of DNA duplexes is desired for many
      applications in nanotechnology or -medicine where DNA is used as a programmable
      building block. Modifications of pyrimidine bases are known to enhance thermal
      stability and have the advantage of standard base-pairing and easy integration
      during chemical DNA synthesis. Through single-molecule force spectroscopy
      experiments with atomic force microscopy and the molecular force assay we
      investigated the effect of pyrimidines harboring C-5 propynyl modifications on
      the mechanical stability of double-stranded DNA. Utilizing these complementary
      techniques, we show that propynyl bases significantly increase the mechanical
      stability if the DNA is annealed at high temperature. In contrast, modified DNA
      complexes formed at room temperature and short incubation times display the same
      stability as non-modified DNA duplexes. 

PMID- 25982590
TI  - Bioequivalence of oral and intravenous carbamazepine formulations in adult
      patients with epilepsy.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and comparative pharmacokinetics
      (PK) of intravenous and oral carbamazepine. METHODS: In this phase 1, open-label
      study, adult patients with epilepsy on a stable oral carbamazepine dosage (400
      2,000 mg/day) were converted to intravenous carbamazepine (administered at 70% of
      the oral dosage). A 28-day outpatient period preceded an up to 10-day inpatient
      period and a 30-day follow-up period. Intravenous carbamazepine was administered
      over 15 or 30 min every 6 h on days 1-7; some patients in the 15-min group were
      eligible to receive four 2- to 5-min (rapid) infusions on day 8. Patients
      underwent blood sampling to determine the area under the concentration-time curve
      (AUC) for carbamazepine and metabolite carbamazepine-10,11-epoxide following oral
      (day 0) and intravenous carbamazepine administration (days 1, 7, and 8).
      Bioequivalence was evaluated in patients with normal renal function (creatinine
      clearance >80 ml/min). Safety assessments were conducted through day 38. RESULTS:
      Ninety-eight patients enrolled and 77 completed the PK component. The mean daily
      oral and intravenous carbamazepine dosage for 64 PK-evaluable patients with
      normal renal function was 962.5 and 675.1 mg (70% of oral dosage), respectively.
      Steady-state minimum concentration (C(min)) and overall exposure (AUC0-24) for
      intravenous carbamazepine infused over 30, 15, or 2-5 min were similar to oral
      carbamazepine. The 90% confidence intervals (CIs) for the ratios of the adjusted
      means for AUC0-24, maximum concentration (Cmax), and C(min) were within the 80%
      125% bioequivalence range for 30-min intravenous infusions versus oral
      administration, but exceeded the upper limit for Cmax for the 15-min and rapid
      infusions. All intravenous carbamazepine infusions were well tolerated.
      SIGNIFICANCE: Intravenous carbamazepine infusions (70% of oral daily dose) of 30
      , 15-, and 2- to 5-min duration, given every 6 h, maintained patients' plasma
      carbamazepine concentrations. Intravenous carbamazepine 30-min infusions were
      bioequivalent to oral carbamazepine in patients with normal renal function; rapid
      infusions were well-tolerated in this study.

PMID- 25982592
TI  - Puncture mechanics of soft solids.
AB  - Gels and other soft elastic networks are a ubiquitous and important class of
      materials whose unique properties enable special behavior, but generally elude
      characterization due to the inherent difficulty in manipulating them. An example
      of such behavior is the stability of gels to large local deformations on their
      surface. This paper analyzes puncture of model soft materials with particular
      focus on the force response to deep indentation and the critical load for
      material failure. Large-strain behavior during deep indentation is described with
      a neo-hookean contact model. A fracture process zone model is applied to the
      critical load for puncture. It is found that the indenter geometry influences the
      size of the fracture process zone, resulting in two distinct failure regimes:
      stress-limited and energy-limited. The methods outlined in this paper provide a
      simple means for measuring Young's modulus, E, as well as the material's maximum
      cohesive stress, sigma0, fracture energy, Gamma0, and the intrinsic length scale
      linking the two, l0, all without requiring specialized sample preparation. 

PMID- 25982591
TI  - Catheter ablation of pediatric AV nodal reentrant tachycardia: results in small
      children.
AB  - BACKGROUND: AV nodal reentrant tachycardia (AVNRT) is commonly encountered in
      pediatric patients. Definite treatment can be achieved by catheter ablation. The
      purpose of the study was to evaluate the efficacy and safety of AVNRT ablation
      focusing on children with a body weight <=25 kg. PATIENTS AND RESULTS: Catheter
      ablation of AVNRT was attempted in 253 patients. Median age was 12.5 years;
      median body weight was 48.7 kg. 25 (9.9 %) children had a body weight <=25 kg.
      Congenital heart disease was present in 6 patients (2.4 %). Procedural success
      was achieved in 98 % using radiofrequency, in 100 % using cryoenergy alone, and
      in 94 % using both energy sources. In patients with a body weight <=25 kg,
      success was achieved in 96 %. In patients <=25 kg, fluoroscopy and procedure
      duration did not differ from those >25 kg. The rate of major complications was
      significantly higher in the patients <=25 kg (12 vs. 2.2 %, p = 0.04). Permanent
      AV block after RF ablation occurred in 2 patients with congenital heart disease
      and one infant with a body weight of 8.7 kg. CONCLUSIONS: Catheter ablation of
      AVNRT in children and adolescents was safe and effective. Infants and small
      children with a body weight <=25 kg had a higher prevalence of serious
      complications. This should alert physicians in decision making toward catheter
      ablation in these patients. In patients with congenital heart disease and
      different anatomy of the cardiac conduction system, operators must be aware of an
      increased risk for AV block.

PMID- 25982593
TI  - Hibernoma as an incidental finding on (18)F-FDG-PET/CT in lymphoma patient follow
      up.

PMID- 25982594
TI  - Biomechanical gait features associated with hip osteoarthritis: Towards a better
      definition of clinical hallmarks.
AB  - Critical appraisal of the literature highlights that the discriminative power of
      gait-related features in patients with hip osteoarthritis (OA) has not been fully
      explored. We aimed to reduce the number of gait-related features and define the
      most discriminative ones comparing the three-dimensional gait analysis of 20
      patients with hip osteoarthritis (OA) with those of 17 healthy peers. First,
      principal component analysis was used to reduce the high-dimensional gait data
      into a reduced set of interpretable variables for further analysis, including
      tests for group differences. These differences were indicative for the selection
      of the top 10 variables to be included into linear discriminant analysis models
      (LDA). Our findings demonstrated the successful data reduction of hip
      osteoarthritic-related gait features with a high discriminatory power. The
      combination of the top variables into LDA models clearly separated groups, with a
      maximum misclassification error rate of 19%, estimated by cross-validation.
      Decreased hip/knee extension, hip flexion and internal rotation moment were gait
      features with the highest discriminatory power. This study listed the most
      clinically relevant gait features characteristics of hip OA. Moreover, it will
      help clinicians and physiotherapists understand the movement pathomechanics
      related to hip OA useful in the management and design of rehabilitation
      intervention.

PMID- 25982596
TI  - Gas-containing gallstones: a radiological finding.

PMID- 25982595
TI  - Position paper from the Spanish Society of Rheumatology on biosimilar drugs.
AB  - A biosimilar (BS) is a biological drug that contains a version of the active
      substance of an already authorized original biological product. The BSs are
      marketed after patent period of the original drug has ended and once it has been
      demonstrated that the differences regarding the innovative medicine have no
      relevant effect on its safety or clinical efficacy. The Spanish Society of
      Rheumatology, in line with the European Medicines Agency, considers that because
      of its nature and complexity of production, a BS cannot be considered to be the
      same as a generic drug. The Spanish Society of Rheumatology expresses an
      unequivocal commitment to the sustainability of the health system in our country
      and our steadfast alignment with all measures designed to ensure continuity,
      without reducing the quality of care. Therefore, we believe that the advent of
      BSs will likely facilitate access of patients with rheumatic diseases to the
      biological drugs. This article reviews the European Medicines Agency requirements
      for authorization, the Spanish legal framework and controversies on BS and
      presents the position paper of the Spanish Society of Rheumatology on these
      drugs. 

PMID- 25982597
TI  - Interesterified fat or palm oil as substitutes for partially hydrogenated fat
      during the perinatal period produces changes in the brain fatty acids profile and
      increases leukocyte-endothelial interactions in the cerebral microcirculation
      from the male offspring in adult life.
AB  - We investigated whether maternal intake of normolipidic diets with distinct fatty
      acid (FA) compositions alters the lipidic profile and influences the inflammatory
      status of the adult offsprings' brains. C57BL/6 female mice during pregnancy and
      lactation received diets containing either soybean oil (CG), partially
      hydrogenated vegetable fat rich in trans-fatty acids (TG), palm oil (PG), or
      interesterified fat (IG). After weaning, male offspring from all groups received
      control diet. The FA profile was measured in the offspring's brains at post-natal
      days 21 and 90. Brain functional capillary density as well as leukocyte
      endothelial interactions in the cerebral post-capillary venules was assessed by
      intravital fluorescence microscopy at post-natal day 90. Inflammation signaling
      was evaluated through toll-like receptor 4 (TLR4) content in brain of the adult
      offspring. In the 21-day old offspring, the brains of the TG showed higher levels
      of trans FA and reduced levels of linoleic acid (LA) and total n-6
      polyunsaturated fatty acids (PUFA). At post-natal day 90, TG and IG groups showed
      reduced levels of eicosapentaenoic acid (EPA) and total n-3 PUFA tended to be
      lower compared to CG. The offspring's brains exhibited an altered
      microcirculation with increased leukocyte rolling in groups TG, PG and IG and in
      TG group increased leukocyte adhesion. The TLR4 content of TG, IG and PG groups
      only tended to increase (23%; 20% and 35%, respectively). Maternal consumption of
      trans FA, palm oil or interesterified fat during pregnancy and lactation can
      trigger the initial steps of inflammatory pathways in the brain of offspring in
      adulthood.

PMID- 25982599
TI  - Antifungal effect of Trachyspermum ammi against susceptible and fluconazole
      resistant strains of Candida albicans.
AB  - OBJECTIVE: Trachyspermum ammi (T. ammi) has been known as having many therapeutic
      properties and its antimicrobial activity has currently received a renewed
      interest. This study aimed to verify the effectiveness of T. ammi essential oil
      to inhibit the growth of Candida albicans (C. albicans) strains isolated from
      HIV(+) patients with oropharyngeal candidiasis (OPC). MATERIALS AND METHODS: The
      essential oil was obtained by hydrodistillation in a Clevenger apparatus and
      analyzed by gas chromatography. Susceptibility tests were expressed as inhibition
      zone by the disk diffusion method and minimal inhibitory concentration (MIC) and
      minimal fungicidal concentration (MFC) by the broth microdilution method.
      RESULTS: Thymol (63.4%), p-cymene (19%) and gamma-terpinen (16.9%) were found as
      the most abundant constituents. The disk diffusion results revealed that 67% of
      oral C. albicans isolates were susceptible, 9% susceptible-dose dependent and 24%
      resistant to fluconazole. In the broth microdilution method, 68% of isolates were
      susceptible, 5% susceptible-dose dependent and 27% resistant to fluconazole. The
      increase in concentration led to a significant reduction in yeasts that were
      growing in exponential phase. In addition, with increasing in T. ammi oil
      concentration, the time of remaining cells in lag phase was significantly
      increased. CONCLUSION: This study showed that all clinical C. albicans isolates
      were susceptible to T. ammi essential oil, indicating a significant reduction in
      the yeast growth in exponential phase.

PMID- 25982600
TI  - [Current concepts in breast cancer].

PMID- 25982602
TI  - [Ocular Trauma Score comparison with open globe receiving early or late care
      attention].
AB  - BACKGROUND: The Ocular Trauma Score (OTS) is a scale that estimates the prognosis
      of injured eyes after treatment, whose results are consistent with those of
      longitudinal studies. The time between injury presentation and initial care has
      been described as a prognostic factor for visual outcome, but the OTS features of
      eyes receiving early or late care after trauma have not been compared. MATERIAL
      AND METHODS: Non-experimental, comparative, retrospective, cross sectional study.
      Patients from either gender, aged 5-80 years, with open globe trauma, without
      previous diseases that reduced visual acuity or previous intraocular surgery were
      included. The distribution of the OTS variables was identified. The sample was
      divided in two: group 1 (time between trauma occurrence and initial care <= 24
      hours) and 2 (time > 24 hours). The frequency of OTS categories of unfavorable
      prognosis (1-3) was compared between groups (chi(2)). RESULTS: 138 eyes of 138
      patients, mean age 28.8 years, 65.2% male. The evolution time ranged 2-480 hours
      (mean 39.9); 103 eyes were assigned to group 1 (74.6%), and 35 to group 2
      (25.4%). The proportion of categories 1-3 in group 1 (82.5%, n = 85) did not
      differ from that in group 2 (80%, n = 28; p = 1.0). CONCLUSION: The proportion of
      OTS categories with unfavorable prognosis did not show significant differences
      between the eyes who received care before or after 24 hours that could contribute
      to a different outcome, besides the delay in starting treatment.

PMID- 25982601
TI  - [Efficacy of dorzolamide in reducing retinal thickness after photocoagulation in
      diabetic macular oedema].
AB  - BACKGROUND: Focal photocoagulation interrupts vascular leakage in diabetic
      macular edema, and allows the retinal pigment epithelium to withdraw fluid that
      thickens the retina; this mechanism could be enhanced by dorzolamida, a topical
      carbonic anhydrase inhibitor. OBJECTIVE: To determine the efficacy of dorzolamida
      compared against placebo, in reducing retinal thickness after focal
      photocoagulation, in eyes with diabetic macular oedema. MATERIAL AND METHODS:
      Experimental, comparative, prospective, longitudinal, double blind study in
      diabetics with focal macular oedema treated with photocoagulation. Treated eyes
      were randomly assigned three weeks after the procedure to receive dorzolamide
      (group 1) or placebo (group 2), three times daily during three weeks. Means of
      visual acuity, center point thickness and macular volume were compared 3 and 6
      weeks after photocoagulation within groups (Wilcoxon's t) and between groups
      (Mann-Whitneys's U). RESULTS: Sixty-nine eyes form patients aged 58.3 +/- 8.3
      years; 37 were assigned to group 1 and 42 to group 2. Mean center point thickness
      changed from 178.4 +/- 34MUm to 170 +/- 29.1MUm in group 1 (p = 0.04), and from
      179.2 +/- 22.4MUm to 178.6 +/- 20.8MUm in group 2 (p = 0.7); mean macular volume
      changed from 7.63 +/- 0.52mm(3) to 7.50 +/- 0.50mm(3) in group 1 (p = 0.02) and
      from 7.82 +/- 0.43mm(3) to 7.76 +/- 0.42mm(3) in group 2 (p = 0.014).
      CONCLUSIONS: The efficacy of dorzolamide was higher than that of placebo, to
      reduce retinal thickness after focal photocoagulation in diabetics with macular
      oedema.

PMID- 25982603
TI  - [Ultrasound-guided continuous infraclavicular block for hand surgery: technical
      report arm position for perineural catheter placement].
AB  - BACKGROUND: Continuous perineural infusion of local anesthetic provides better
      postoperative analgesia than intravenous administration of opioids or NSAIDs in
      upper limb surgery. The infraclavicular approach is a good option due to the
      muscular stability to catheter; the abduction of the arm apparently makes more
      superficial the brachial plexus and which elevates clavicle cephalad. AIM: The
      aim of this study was to identify whether the abduction of the arm for to
      decreases the skin-plexus distance, facilitating it catheter insertion in a
      perineural way for a better analgesia. This relation between the arm and the
      colocation of catheter has not yet been established. MATERIAL AND METHODS: We
      included 58 adult patients, undergoing forearm and hand surgery, initially
      divided into two groups, adduction and abduction. It was placed continuous
      infraclavicular block guided by ultrasound, it allow the catheter tip was
      adjacent to the posterior cord. In the group patients with high technical
      difficulties were allowed to reposition the arm abduction, recording number of
      punctures, redirects, ease of insertion of the catheter and skin-plexus distance.
      RESULTS: The abduction of the arm moved the clavicle toward cephalad and
      separated it from the linear transducer, this allowed to maneuver the needle
      right angle and redirect it, the distance skin-plexus did not decrease
      significantly with arm position. CONCLUSIONS: Arm abduction allows better
      scanning facilitates the infraclavicular puncture and catheter introduction.

PMID- 25982598
TI  - The evolving roles of pericyte in early brain injury after subarachnoid
      hemorrhage.
AB  - Despite accumulated understanding on the mechanisms of early brain injury and
      improved management of subarachnoid hemorrhage (SAH), it is still one of the
      serious and refractory health problems around the world. Traditionally, pericyte,
      served as capillary contraction handler, is recently considered as the main
      participant of microcirculation regulation in SAH pathophysiology. However,
      accumulate evidences indicate that pericyte is much more than we already know.
      Therefore, we briefly review the characteristics, regulation pathways and
      functions of pericyte, aim to summarize the evolving new pathophysiological roles
      of pericyte that are implicated in early brain injury after SAH and to improve
      our understanding in order to explore potential novel therapeutic options for
      patients with SAH. This article is part of a Special Issue entitled SI: Cell
      Interactions In Stroke. 

PMID- 25982605
TI  - [Clinical and epidemiological characteristics of humeral supracondylar fractures
      in pediatric patients in a Regional General Hospital].
AB  - BACKGROUND: Supracondylar humerus fractures are common in children between 5-7
      years of age and more frequent in the males, 90-95% of these fractures are in
      extension mechanism, the urgency of immediate attention is to prevent
      complications and sequelae. OBJECTIVE: To establish the clinical and
      epidemiological profile of supracondylar humerus fractures, in a General Regional
      Hospital from the Instituto Mexicano del Seguro Social in Yucatan Mexico, during
      2011-2013. MATERIAL AND METHODS: A cross-sectional study. Strength association
      was measured by odds ratios and statistical significance with chi(2) test, p
      value was considered in < 0.05 RESULTS: 56 cases were analyzed, the mean age was
      2.6 +/- 5.33 years, the mechanism of injury was falling over at home, male gender
      is associated with extent injure mechanism (OR 5.6, 95% CI 1.0-30.1, p = 0.03),
      we observed that at most time elapsed between injury and medical means more
      hospital days (r = 0.40; p = 0.002), surgical treatment was established in 44
      cases (78.6%), 18 (40.9%) with closed technique and placement of cloves and 26
      (59.1%) with open reduction, in 100% cross configuration was used, ten
      complications were reported. CONCLUSIONS: Supracondylar humerus fractures are a
      common injury in children, males are more likely to be injured by extension, and
      the speed in medical treatment is an important issue.

PMID- 25982604
TI  - [Unstable thorax fixation with bioabsorbable plates and screws. Presentation of
      some cases].
AB  - BACKGROUND: Flail chest is managed with mechanical ventilation or inhalation
      therapy, and analgesia. Mechanical ventilations carry risks by themselves and
      disengage with the external fixators so they must be operated to improve lung
      ventilatory mechanics and cleaning. Little has been published on the use of
      bioabsorbable material and its evolution in the setting of flail chest. MATERIAL
      AND METHODS: A material that did had to be retired, that presented the
      malleability of titanium and its inflammatory reaction was minimal and could be
      handled in both adults and children was investigated. Here is shown a descriptive
      study of patients with flail chest under rib fixation with plates and
      bioabsorbable screws. RESULTS: 18 cases are presented, aged 33-74 years, three
      with bilateral flail chest; fixation was performed between days 1-21 of the
      accident. In cases that showed no fractures pelvic limbs, gait next day restarted
      fi ng in all cases improved mechanical ventilation, pain decreased, none has so
      far presented reaction material. CONCLUSIONS: Flail chest has a high (16.3%)
      mortality when no management provides the pathophysiology of the condition (pain,
      poor mechanical ventilation, alveolar edema-pulmonary contusion). The use of
      bioabsorbable material has no side effects attributable to material which is
      another option for rib fixation.

PMID- 25982606
TI  - [Association analysis of SNP-63 and indel-19 variant in the calpain-10 gene with
      polycystic ovary syndrome in women of reproductive age].
AB  - BACKGROUND: Polycystic ovary syndrome is a complex and heterogeneous disease
      involving both reproductive and metabolic problems. It has been suggested a
      genetic predisposition in the etiology of this syndrome. The identification of
      calpain-10 gene (CAPN10) as the first candidate gene for type 2 diabetes
      mellitus, has focused the interest in investigating their possible relation with
      the polycystic ovary syndrome, because this syndrome is associated with
      hyperinsulinemia and insulin resistance, two metabolic abnormalities associated
      with type 2 diabetes mellitus. OBJECTIVE: To investigate if there is association
      between the SNP-63 and the variant indel-19 of the CAPN10 gene and polycystic
      ovary syndrome in women of reproductive age. MATERIAL AND METHODS: This study
      included 101 women (55 with polycystic ovary syndrome and 46 without polycystic
      ovary syndrome). The genetic variant indel-19 was identified by electrophoresis
      of the amplified fragments by PCR, and the SNP-63 by PCR-RFLP. RESULTS: The
      allele and genotype frequencies of the two variants do not differ significatly
      between women with polycystic ovary syndrome and control women group. The
      haplotype 21 (defined by the insertion allele of indel-19 variant and C allele of
      SNP-63) was found with higher frequency in both study groups, being more frequent
      in the polycystic ovary syndrome patients group, however, this difference was not
      statistically significant (p = 0.8353). CONCLUSIONS: The results suggest that SNP
      63 and indel-19 variant of the CAPN10 gene do not represent a risk factor for
      polycystic ovary syndrome in our patients group.

PMID- 25982607
TI  - [Acetazolamide in the resolution of cerebrospinal fluid cutaneous fistula after
      peridural analgesia: case report].
AB  - BACKGROUND: Cerebrospinal fluid cutaneous fistula following spinal anesthesia is
      a serious and rare complication which mandates prompt diagnosis, although the
      treatment modalities are not well codified. CLINICAL CASE: Female aged 50 with a
      stage IIB cervical carcinoma; a peridural catheter was passed at lumbar level;
      three days after surgery, refers severe headache and to corroborate leakage
      cerebrospinal fluid through the puncture. The prescription was antibiotics and
      acetazolamide 250mg every 8hours for five days with favorable evolution.
      CONCLUSION: In this case, management with acetazolamide and suture of the fistula
      inhibits cerebrospinal fluid leakage without blood patch.

PMID- 25982608
TI  - [Gastro-bronchial fistula major complication of sleeve gastrectomy].
AB  - BACKGROUND: Gastrobronchial fistula is a rare complication in gastroesophageal
      surgical procedures. It is difficult to diagnose and handling is complex.
      Therefore, there have been developments for non-surgical alternatives to
      obliterate minor fistula mortality. Endoscopic treatment is an option for
      patients with small fistulas or in serious condition. CLINICAL CASE: A 38 year
      old woman with evidence of gastrobronchial fistula postoperated of gastric
      sleeve, diagnosed during the postoperative period due to clinical variegated was
      initially handled as infectious respiratory symptoms; once the fistulous path was
      established, the intention was to close the path using endoclips. However, adding
      hemopneumothorax, drainage tube placement and thoracotomy were required. It was
      decided to chose a prosthetic esophageal endoscopic management of
      polytetraflouroethylene and fibrin as last therapy, because the patient had
      systemic inflammatory response syndrome, with favorable response to endoscopic
      management. DISCUSSION: Bariatric surgery has shown satisfactory results,
      however, the complexity of the procedure favors severe complications such as the
      present case. Gastrobronchial fistulas represent a diagnostic and therapeutic
      challenge, this is considering from a conservative management to endoscopic
      procedures, as in our patient. CONCLUSION: Although gastrobronchial fistulas are
      a rare complication, the use of endoscopy in resolution should be a first class
      weapon in its management, since it offers a lower morbidity in a patient with
      habitual respiratory symptoms that are difficult to control, with satisfactory
      results in the medium and long term.

PMID- 25982609
TI  - [Hepatocellular carcinoma originated in the caudate lobe. Surgical strategy for
      resection. A propos of a case].
AB  - BACKGROUND: Hepatocellular carcinoma originating from the caudate lobe has a
      worse prognosis than other hepatocellular carcinoma in another segment of the
      liver. An isolated caudate lobe resection of the liver represents a significant
      technical challenge. Caudate lobe resection can be performed along with a
      lobectomy or as an isolated liver resection. There are very few reports about
      isolated caudate lobe liver resection. We report a case of successful isolated
      resection of hepatocellular carcinoma in the caudate lobe with excellent long
      term survival. CLINICAL CASE: A 74 years old female with 8cm mass lesion in the
      caudate lobe without clinical or biochemical evidence of liver cirrhosis, serum
      alpha-fetoprotein 3.7 U/l, and negative hepatitis serology was evaluated for
      surgery. Complete resection of the lesion in 270minutes with Pringle maneuver for
      13minutes was satisfactorily performed. Patient was discharged ten days after
      surgery without complications. Patient is currently asymptomatic, without
      deterioration of liver function and 48 month tumor free survival after the
      procedure. CONCLUSION: Isolated caudate lobe resection is an uncommon but
      technically possible procedure. In order to achieve a successful resection, one
      must have a detailed knowledge of complete liver anatomy. Tumor free margins must
      be obtained to provide long survival for these patients who have a malignancy in
      this anatomic location.

PMID- 25982610
TI  - [Emphysematous gastritis secondary to gastric mucormycosis].
AB  - BACKGROUND: Mucormycosis is a rare fungal infection of the mucorales order, which
      affects mostly immunocompromised patients. The association with emphysematous
      gastritis is rare and often fatal produced by gas -forming bacteria. We report
      the case of a trauma patient with type 1 diabetes mellitus, and diabetic
      ketoacidosis complicated with gastric mucormycosis associated with emphysematous
      gastritis. CLINICAL CASE: A male aged 32 who is involved in a car accident, who
      suffered head trauma, is admitted to the Intensive Care Unit, presenting diabetic
      ketoacidosis and upper gastrointestinal bleeding. An endoscopy was performed and
      an erosive esophagitis Class C, ischemia and gastric necrosis was found. A
      computed tomography scan showed emphysematous gastritis and gastric necrosis. He
      underwent total gastrectomy with a histopathology report of gastric mucormycosis.
      After the surgical procedure the patient died because of sepsis secondary to
      pulmonary mucormycosis DISCUSSION: Mucormycosis is a rare fungical disease which
      infrequently affects the gastrointestinal tract, being the stomach the most
      affected site. The mortality is high if the diagnosis is not done promptly and
      appropriate treatment is given. CONCLUSION: Suspecting its existence is necessary
      in patients with immunocompromised status to diagnose and provide timely
      treatment to increase survival, because of its high mortality.

PMID- 25982611
TI  - [Spontaneous cholecystocutaneous fistula].
AB  - BACKGROUND: Spontaneous cholecystocutaneous fistula is defined as a gallbladder
      communication with the external environment through the abdominal wall rupture;
      the first reports were written in the seventeenth century by Thilesus. During the
      past 50 years 25 cases have been reported. CLINICAL CASE: We report a case of a
      30-year-old woman presented with a five-year history of biliary colic, six months
      prior to medical assessment presents outlet of biliary material and gallstones
      spontaneously in the right upper quadrant. Fistulogram was performed without
      evidence of obstruction, subsequently cholecystectomy and resection of the
      fistula was performed. DISCUSSION: The biliary fistulas are an abnormal
      communication from the gallbladder into another surface, is a rare condition in
      our day as it only occurs in 10% of patients with gallbladder lithiasis; while
      spontaneous cholecystocutaneous fistula clinic is more than evident. It is
      imperative perform studies like ultrasound, tomography, and fistulogram. The
      mainstay of treatment is cholecystectomy, resection of the fistula and repair of
      abdominal wall defect. CONCLUSION: The incidence of cholecystocutaneous fistula
      today is minimal and it seems that the current trend is to become an entity
      anecdotal, the approach subcostal abdominal examination remains as the first
      choice. The laparoscopic approach is an option reserved for the experienced
      surgeon.

PMID- 25982612
TI  - [L-lactate as a serum marker of intestinal ischemia in patients with complicated
      intestinal obstruction].
AB  - BACKGROUND: The intestinal obstruction secondary to internal hernia is a
      diagnostic challenge. The absence of specific symptoms and signs during clinical
      examination often lead to underestimation of the severity and early surgical
      treatment. The purpose of this article is to review the clinical presentation of
      two patients with internal hernia, describe the clinical, biochemical and
      radiological findings, with emphasis on the L-lactate as an early serum marker of
      intestinal ischemia. CLINICAL CASES: Case 1: female, 44 years history of
      urolithiasis and 2 cesarean sections. Case 2: female, 86 year old with a history
      of open cholecystectomy, incisional and bilateral inguinal hernia repair with
      mesh placement. Both admitted with abdominal pain and intestinal obstruction
      data. The only significant laboratory finding was elevation of L-lactate. The
      abdominal films showed air-fluid levels, dilated loops of small intestine and
      colon. Abdominal contrast tomography showed free abdominal fluid id, internal
      hernia and torque of mesentery. In both cases, exploratory laparotomy was
      performed with bowel resection of ischemic segments, with uneventful recovery.
      CONCLUSIONS: Intestinal ischemia secondary to internal hernia is difficult lt to
      diagnose. In patients with a high suspicion, signs of intestinal obstruction by
      plain radiography, the elevation of L-lactate, could help in the early diagnosis
      of intestinal ischemia and immediate surgical treatment.

PMID- 25982613
TI  - [Cecal perforation secondary to surgical drainage. A case report].
AB  - BACKGROUND: The use of surgical drains in abdominal surgery is still today
      controversial. While accepting their role in certain circumstances, their
      systematic use advocated by other schools, is not fully accepted. We present a
      case of secondary blind drilling drainage tube perineum following an
      abdominoperineal amputation of the rectum that forced a surgical repair in a
      neoplastic patient CLINICAL CASE: This is a patient who underwent abdomino
      perineal resection for rectal neoplasia. It was decided to leave a silicone-type
      drain tube for perineum and in late postoperative he presented cecum perforation
      due to traumatic introduction thereof into the cecal light, which forced his
      reoperation and surgical repair. DISCUSSION: There is a tendency to use less and
      less drains in abdominal surgery, although there are certain occasions when it
      becomes inevitable. On the other hand it entails morbidity associated with its
      use that significantly complicates and delays the recovery of the patient. It is
      accepted that is not useful to prevent the occurrence of fistulas, although it
      contributes to its early detection. CONCLUSIONS: The cecal perforation due to
      drain is a rare complication which must always be taken into account, and that
      perhaps could be avoided by using soft and less rigid drains.

PMID- 25982614
TI  - [Eccentric strength training for the rotator cuff tendinopathies with subacromial
      impingement. Current evidence].
AB  - BACKGROUND: Rotator cuff tears are the leading cause of pain and functional
      disability of the shoulder. Conservative treatment is an essential part of their
      management. Despite the limited evidence, rehabilitation is the mainstay of the
      treatment for rotator cuff tears associated to impingement syndrome. There are
      current reports on the utility of strengthening with resistance, particularly by
      eccentric exercise. OBJECTIVE: This report aims to present an overview of the
      efficacy of eccentric exercises in tendinopathies and current evidence of its
      benefit in rotator cuff tears. METHODS AND RESULTS: We describe the information
      available in tendinopathy and analyzed four studies published on eccentric
      strengthening for rotator cuff tears. There is theoretical evidence about its
      usefulness in this pathology, but only a controlled clinical trial has been
      published with data on improvement in strength but not in pain or functionality.
      CONCLUSIONS: More studies are needed with better methodological designs in order
      to generate evidence of their utility and recommendation.

PMID- 25982615
TI  - [The dimension of the paradigm of complexity in health systems].
AB  - This article presents elements to better understand health systems from the
      complety paradigm, innovative perspective that offers other ways in the
      conception of the scientific knowledge prevalent away from linear, characterized
      by the arise of emerging dissociative and behaviors, based on the intra and trans
      disciplinarity concepts such knowledges explain and understand in a different way
      what happens in the health systems with a view to efficiency and effectiveness.
      The complexity paradigm means another way of conceptualizing the knowledge, is
      different from the prevalent epistemology, is still under construction does not
      separate, not isolated, is not reductionist, or fixed, does not solve the
      problems, but gives other bases to know them and study them, is a different
      strategy, a perspective that has basis in the systems theory, informatics and
      cybernetics beyond traditional knowledge, the positive logics, the newtonian
      physics and symmetric mathematics, in which everything is centered and balanced,
      joint the "soft sciences and hard sciences", it has present the Social
      Determinants of Health and organizational culture. Under the complexity paradigm
      the health systems are identified with the following concepts: entropy,
      neguentropy, the thermodynamic second law, attractors, chaos theory, fractals,
      selfmanagement and self-organization, emerging behaviors, percolation,
      uncertainty, networks and robusteness; such expressions open new possibilities to
      improve the management and better understanding of the health systems, giving
      rise to consider health systems as complex adaptive systems.

PMID- 25982616
TI  - [The origin of the "simplified gastric bypass"].

PMID- 25982617
TI  - Carta al editor.

PMID- 25982618
TI  - Digging Deeper: A Case Study of Farmer Conceptualization of Ecosystem Services in
      the American South.
AB  - The interest in improved environmental sustainability of agriculture via
      biodiversity provides an opportunity for placed-based research on the
      conceptualization and articulation of ecosystem services. Yet, few studies have
      explored how farmers conceptualize the relationship between their farm and nature
      and by extension ecosystem services. Examining how farmers in the Southern
      Piedmont of South Carolina discuss and explain the role of nature on their farm,
      we create a detail-rich picture of how they perceive ecosystem services and their
      contributions to the agroeconomy. Using 34 semi-structured interviews, we
      developed a detail-rich qualitative portrait of these farmers' conceptualizations
      of ecosystem services. Farmers' conceptualization of four ecosystem services:
      provisioning, supporting, regulating, and cultural are discussed, as well as
      articulation of disservices. Results of interviews show that most interviewees
      expressed a basic understanding of the relationship between nature and
      agriculture and many articulated benefits provided by nature to their farm.
      Farmers referred indirectly to most services, though they did not attribute
      services to biodiversity or ecological function. While farmers have a general
      understanding and appreciation of nature, they lack knowledge on specific ways
      biodiversity benefits their farm. This lack of knowledge may ultimately limit
      farmer decision-making and land management to utilize ecosystem services for
      environmental and economic benefits. These results suggest that additional
      communication with farmers about ecosystem services is needed as our
      understanding of these benefits increases. This change may require collaboration
      between conservation biology professionals and extension and agriculture
      professionals to extended successful biomass provisioning services to other
      ecosystem services. 

PMID- 25982619
TI  - Compost Amendment Enhances Natural Revegetation of a Mediterranean Degraded
      Agricultural Soil.
AB  - A vegetation analysis was carried out on a degraded agricultural soil of the
      Mediterranean area (Campania region, southern Italy) in order to study the
      effects of different fertilization practices (quality compost, mineral
      fertilizers, mixed fertilization, and no fertilization) on the whole spontaneous
      vegetation community. The study was performed for two consecutive years at three
      different scales (species level, community structure, and community properties),
      using three different units of abundance (number of individuals, biomass, and
      cover of each species). The observations were carried out in spring, after 5 and
      6 years of soil treatments, on a total area of 4 m(2) for each soil treatment and
      in each year. The different fertilization practices did not determine changes in
      species composition; however, the relative abundance of dominant species
      increased in compost and mixed fertilized soils, particularly in the second year
      of observation. Although the dominance and diversity were unaffected by the
      different fertilization practices, the total biomass and total number of
      individuals increased in compost-amended soils. These results indicate the
      effectiveness of soil quality compost amendments to enhance natural revegetation,
      a key step in the recovery of degraded areas.

PMID- 25982620
TI  - Erratum to: Riparian Land-Use and Rehabilitation: Impact on Organic Matter Input
      and Soil Respiration.

PMID- 25982622
TI  - Understand, respect and restore anatomy as close as possible!

PMID- 25982621
TI  - The relationship between the presence of depressive symptoms and the severity of
      self-reported knee pain in the middle aged and elderly.
AB  - PURPOSE: Knee pain is a very common symptom of knee osteoarthritis (OA), and
      identification of the major contributors to knee pain is important to establish
      management plans for patients with knee OA. Among the potential contributors, we
      hypothesized that coexisting depressive symptoms might increase the severity of
      knee pain because the increased cytokine levels and neurotransmitter changes
      related to depression are known to influence the threshold of physical pain
      perception. Therefore, a possible relationship between self-reported depressive
      symptoms and self-reported knee pain has been explored. Additionally, we sought
      to determine factors influencing the severity of knee pain in a middle-aged and
      elderly Korean population using data from the fifth Korean National Health and
      Nutrition Examination Survey. METHODS: In total, 6599 persons aged >=50 years
      were evaluated in terms of the radiographic severity of OA and pain severity
      using 10-point numerical rating scales. Depressive mood was assessed using a
      polar question: "Had the subject felt despair or depression every day for more
      than 2 weeks during the past year?" RESULTS: The Kellgren-Lawrence knee OA grade,
      depression, gender, educational level, household income, smoking status, marital
      status, living place, comorbidity status, BMI, and age were identified by
      multiple linear regression as variables affecting knee pain severity. The
      presence of depressive symptoms was associated with an increased risk of severe
      knee pain (odds ratio 2.55 [95 % confidence interval 1.77-3.66]). After
      stratifying the group in terms of the radiographic severity of knee OA, the
      relationship with depression persisted in the minimal (2.89 [1.90-4.32]) and
      moderate OA subgroups (2.29 [1.33-3.94]), but not in the severe OA subgroup.
      CONCLUSIONS: Severe knee pain was independently associated with the presence of
      depressive symptoms in middle-aged and elderly Korean subjects. This suggests
      that screening for and treatment of depression may help improve knee pain in
      elderly individuals. LEVEL OF EVIDENCE: II.

PMID- 25982623
TI  - Professional football can be considered a healthy sport?
AB  - PURPOSE: This study aimed to compare the results of knee MRIs of former football
      players with no previous knee surgeries with non-regular practitioners of impact
      sports, matched by age and sex, and combine these results with other variables
      such as current quality of life and pain in the knees. METHODS: The study
      participants were 16 male former professional football players and 21 male
      volunteers from different non-sports professional areas. All participants
      underwent bilateral magnetic resonances. Specific knee evaluations with regard to
      osteoarthritis and quality of life were performed in both groups by applying the
      Knee Injury and Osteoarthritis Outcome Score (KOOS) subjective questionnaires and
      SF-36, respectively. RESULTS: The between-group comparison revealed significant
      differences on: pain, symptoms, and quality of life related to the knee in KOOS
      subscales; physical aspects and vitality subscale of SF-36; and former soccer
      players had worst magnetic resonances scores than controls. CONCLUSION: Results
      of this study indicate probable specific adverse effects associated with
      participating in professional football. LEVEL OF EVIDENCE: Cross-sectional study,
      Level III.

PMID- 25982624
TI  - Arthroscopic anterior talofibular ligament repair for lateral instability of the
      ankle.
AB  - Although several arthroscopic procedures for lateral ligament instability of the
      ankle have been reported recently, it is difficult to augment the reconstruction
      by arthroscopically tightening the inferior extensor retinaculum. There is also
      concern that when using the inferior extensor retinaculum, this is not strictly
      an anatomical repair since its calcaneal attachment is different to that of the
      calcaneofibular ligament. If a ligament repair is completed firmly, it is
      unnecessary to add argumentation with inferior extensor retinaculum. The authors
      describe a simplified technique, repair of the lateral ligament alone using a
      lasso-loop stitch, which avoids additionally tighten the inferior extensor
      retinaculum. In this paper, it is described an arthroscopic anterior talofibular
      ligament repair using lasso-loop stitch alone for lateral instability of the
      ankle that is likely safe for patients and minimal invasive. LEVEL OF EVIDENCE:
      Therapeutic study, Level V.

PMID- 25982625
TI  - The Elbow Self-Assessment Score (ESAS): development and validation of a new
      patient-reported outcome measurement tool for elbow disorders.
AB  - PURPOSE: To develop and validate an elbow self-assessment score considering
      subjective as well as objective parameters. METHODS: Each scale of the American
      Shoulder and Elbow Surgeons-Elbow Score, the Broberg and Morrey rating system
      (BMS), the Patient-Rated Elbow Evaluation (PREE) Questionnaire, the Mayo Elbow
      Performance Score (MEPS), the Oxford Elbow Score (OES) and the Quick Disabilities
      of the Arm, Shoulder and Hand (Quick-DASH) was analysed, and after matching of
      the general topics, the dedicated items underwent a fusion to the final ESAS's
      item and a score containing 22 items was created. In a prospective clinical
      study, validity, reliability and responsiveness in physically active patients
      with traumatic as well as degenerative elbow disorders were evaluated. RESULTS:
      Validation study included 103 patients (48 women, 55 men; mean age 43 years). A
      high test-retest reliability was found with intraclass correlation coefficients
      of at least 0.71. Construct validity and responsiveness were confirmed by
      correlation coefficients of -0.80 to -0.84 and 0.72-0.84 (p <0.05). Correlation
      coefficients of the ESAS and well-established elbow rating systems BMS, PREE,
      MEPS, OES and Quick-DASH were between 0.70 and 0.90 (p < 0.05). CONCLUSIONS: With
      this novel Elbow Self-Assessment Score (ESAS), a valid and reliable instrument
      for a qualitative self-assessment of subjective and objective parameters (e.g.
      range of motion) of the elbow joint is demonstrated. Quantitative measurement of
      elbow function may not longer be limited to specific elbow disorders or patient
      groups. The ESAS seems to allow for a broad application in clinical research
      studying elbow patients and may facilitate the comparison of treatment results in
      elbow disorders. The treatment efficacy can be easily evaluated, and treatment
      concepts could be reviewed and revised. LEVEL OF EVIDENCE: Diagnostic study,
      Level III.

PMID- 25982626
TI  - Clinical outcome after total knee replacement.

PMID- 25982627
TI  - Group a rotavirus and norovirus genotypes circulating in the northeastern Brazil
      in the post-monovalent vaccination era.
AB  - Group A rotaviruses (RVA) and noroviruses (NoV) are the leading cause of acute
      gastroenteritis (AGE) worldwide. Childhood diarrhea deaths and hospital
      admissions have declined since the introduction of the monovalent (G1P[8])
      vaccine (Rotarix((r)) [RV1]) in the National Immunization Program in Brazil in
      2006. This study aims to investigate the epidemiological profile of NoV and RVA
      infections from children with AGE in the Northeastern region of Brazil in the
      post vaccine season. Two-hundred fecal samples collected from children up to 10
      years old in Fortaleza, Ceara between 2008-2009 were screened for the presence of
      RVA and NoV. Positive samples were genotyped and sequenced. The RVA screening
      revealed 12% prevalence and all RVA strains belonged to G2P[4] genotype.
      Phylogenetic analysis based on the 11 RVA genome segments sequenced from eight
      samples revealed a DS-1-like genotype constellation: I2-R2-C2-M2-A2-N2-T2-E2-H2.
      For NoV screening, the prevalence observed was 17% and the following genotypes
      were detected: GII.4 (59%), GII.12 (17%), GII.6 (9%), GII.3 (6%), and GII.? (9%).
      At least four different NoVs genotypes and two RVA G2P[4] variants were
      identified circulating in the Northeastern region of Brazil. RVA phylogenetic
      analysis suggests that the RVA G2P[4] strains might have originated from
      intragenogroup reassortment events. Whether the genetic modifications observed in
      these contemporary G2P[4] RVA strains may impact the long-term effectiveness of
      the current vaccination programs remains to be explored. These data reinforce the
      importance of surveillance for monitoring the emergence of new strains of RVA and
      NoV and their impact on cases of acute gastroenteritis.

PMID- 25982628
TI  - Successful response of refractory type I adult-onset pityriasis rubra pilaris
      with ustekinumab and acitretin combination therapy.

PMID- 25982630
TI  - Anti-tumor activities of active ingredients in Compound Kushen Injection.
AB  - Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment
      of tumors, inflammation and other diseases in traditional Chinese medicine.
      Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from
      Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are
      matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological
      activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic
      and cardiovascular protective effects. Recent evidence shows that these compounds
      also produce anti-cancer actions, such as inhibiting cancer cell proliferation,
      inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis,
      inducing cell differentiation, inhibiting cancer metastasis and invasion,
      reversing multidrug resistance, and preventing or reducing chemotherapy- and/or
      radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this
      review, we summarize recent progress in studying the anti-cancer activities of
      MT, OMT and CKI and their potential molecular targets, which provide clues and
      references for further study. 

PMID- 25982632
TI  - The use of short-term central venous catheters for optimizing continuous infusion
      of coagulation factor concentrate in haemophilia patients undergoing major
      surgical procedures.
AB  - INTRODUCTION: Continuous infusion (CI) of clotting factors has facilitated
      surgical procedures and intensive replacement therapy in haemophilia patients.
      This procedure could, however, be further optimized by using a short-term central
      venous catheter (CVCs) instead of via peripheral venous access. AIM: In this
      paper, we present our results on using a short-term CVC in haemophilia patients
      during major surgical operations. METHODS: In total, 40 patients with haemophilia
      A or B (37 and 3, respectively), aged 21-81 years, underwent 67 surgeries with 65
      CVCs. Patients requiring intensive treatment lasting over 5 days had the
      indications for CVC placement. The catheters were placed by experienced
      anaesthesiologists in the operating theatre under general anaesthesia and
      following activated partial thromboplastin time correction. RESULTS: No
      interruption of CI was observed and only one catheter had to be removed
      prematurely due to a suspected infection. There were no signs found for
      prosthesis or wound infection, nor was there any thrombosis documented.
      CONCLUSION: Our study produced encouraging results regarding the use of short
      term CVCs in haemophilia patients. Even though our patient sample was small, the
      data corroborates short-term CVCs to be safe and convenient for factor
      concentrate delivery in CI during major surgical operations.

PMID- 25982633
TI  - Sustainability: orthopaedic surgery wait time management strategies.
AB  - PURPOSE: The purpose of this paper is to examine Canadian organizational and
      systemic factors that made it possible to keep wait times within federally
      established limits for at least 18 months. DESIGN/METHODOLOGY/APPROACH: The
      research design is a multiple cases study. The paper selected three cases: Case 1
      - staff were able to maintain compliance with requirements for more than 18
      months; Case 2 - staff were able to meet requirements for 18 months, but unable
      to sustain this level; Case 3 - staff were never able to meet the requirements.
      For each case the authors interviewed persons involved in the strategies and
      collected documents. The paper analysed systemic and organizational-level
      factors; including governance and leadership, culture, resources, methods and
      tools. FINDINGS: Findings indicate that the hospital that was able to maintain
      compliance with the wait time requirements had specific characteristics: an
      exclusive mandate to do only hip and knee replacement surgery; motivated staff
      who were not distracted by other concerns; and a strong team spirit.
      ORIGINALITY/VALUE: The authors' research highlights an important gradient between
      three cases regarding the factors that sustain waiting times. The paper show that
      the hospital factory model seems attractive in a super-specialized surgery
      context. However, patients are selected for simple surgeries, without
      complications, and so this cannot be considered a unique model.

PMID- 25982631
TI  - The role of the dynorphin/kappa opioid receptor system in anxiety.
AB  - Anxiety disorders are the most common and prevalent forms of psychiatric disease,
      although the biological basis of anxiety is not well understood. The
      dynorphin/kappa opioid receptor system is widely distributed in the central
      nervous system and has been shown to play a critical role in modulating mood and
      emotional behaviors. In the present review, we summarize current literature
      relating to the role played by the dynorphin/kappa opioid receptor system in
      anxiety and kappa opioid receptor antagonists as potential therapeutic agents for
      the treatment of anxiety disorders. 

PMID- 25982634
TI  - Patient assessment of primary care physician communication: segmentation
      approach.
AB  - PURPOSE: The purpose of this paper is to examine how patient assessment of
      primary care physician (PCP) communication is related to patient satisfaction
      with the PCP, patient perception of PCP professional competence, patient
      assessment of the relationship with the doctor and patient demographic
      characteristics using a segmentation approach. DESIGN/METHODOLOGY/APPROACH: The
      authors surveyed 514 adult patients waiting for appointments with their PCPs in
      two US primary care clinics. A latent class analysis was used to identify
      mutually exclusive unobserved homogeneous classes of patients. FINDINGS: The
      authors identified three distinct classes/groups with regard to patient
      assessment of physician communication and the physician-patient relationship. The
      largest group (53 percent of the sample) assessed their PCP communication and
      other doctor-patient relationship aspects as excellent. However, 37 percent
      provided mostly negative assessments, expressed high general dissatisfaction with
      the physician and disagreed with the statement that their PCP was well qualified
      to manage their health problems. These patients were on average more educated and
      affluent and the group included more males. About 10 percent of patients
      expressed generally lower satisfaction with the PCP, though their dissatisfaction
      was not as extreme as in the highly dissatisfied group. RESEARCH
      LIMITATIONS/IMPLICATIONS: Further studies are needed to help physicians develop
      skills to communicate with different patients. ORIGINALITY/VALUE: Patient
      segmentation can be an important tool for healthcare quality improvement
      particularly for emerging approaches to primary care such as patient-centered
      care.

PMID- 25982635
TI  - Implementing hospital quality assurance policies in Iran: balancing licensing,
      annual evaluation, inspections and quality management systems.
AB  - PURPOSE: The purpose of this paper is to provide an overview of applied hospital
      quality assurance (QA) policies in Iran. DESIGN/METHODOLOGY/APPROACH: A mixed
      method (quantitative data and qualitative document analysis) study was carried
      out between 1996 and 2010. FINDINGS: The QA policy cycle forms a tight monitoring
      system to assure hospital quality by combining mandatory and voluntary methods in
      Iran. The licensing, annual evaluation and grading, and regulatory inspections
      statutorily implemented by the government as a national package to assure and
      improve hospital care quality, while implementing quality management systems
      (QMS) was voluntary for hospitals. The government's strong QA policy legislation
      role and support has been an important factor for successful QA implementation in
      Iran, though it may affected QA assessment independency and validity. Increased
      hospital evaluation independency and repositioning, updating standards,
      professional involvement and effectiveness studies could increase QA policy
      impact and maturity. PRACTICAL IMPLICATIONS: The study highlights the current QA
      policy implementation cycle in Iranian hospitals. It provides a basis for further
      quality strategy development in Iranian hospitals and elsewhere. It also raises
      attention about finding the optimal balance between different QA policies, which
      is topical for many countries. ORIGINALITY/VALUE: This paper describes
      experiences when implementing a unique approach, combining mandatory and
      voluntary QA policies simultaneously in a developing country, which has invested
      considerably over time to improve hospital quality. The experiences with a mixed
      obligatory/voluntary approach and comprehensive policies in Iran may contain
      lessons for policy makers in developing and developed countries.

PMID- 25982636
TI  - Small and big quality in health care.
AB  - PURPOSE: The purpose of this paper is to clarify healthcare quality's ontological
      and epistemological foundations; and examine how these lead to different
      measurements and technologies. DESIGN/METHODOLOGY/APPROACH: Conceptual analysis.
      FINDINGS: Small quality denotes conformance to ex ante requirements. Big quality
      includes product and service design, based on customer requirements and
      expectations. Healthcare quality can be divided into three areas: clinical
      decision making; patient safety; and patient experience, each with distinct
      measurement and improvement technologies. PRACTICAL IMPLICATIONS: The conceptual
      model is expected to bring clarity to constructing specific definitions,
      measures, objectives and technologies for improving healthcare.
      ORIGINALITY/VALUE: This paper claims that before healthcare quality can be
      defined, measured and integrated into systems, it needs to be clearly separated
      into ontologically and epistemologically different parts.

PMID- 25982637
TI  - Service quality framework for clinical laboratories.
AB  - PURPOSE: The purpose of this paper is to illustrate a service quality framework
      that enhances service delivery in clinical laboratories by gauging medical
      practitioner satisfaction and by providing avenues for continuous improvement.
      DESIGN/METHODOLOGY/APPROACH: The case study method has been used for conducting
      the exploratory study, with focus on the Mauritian public clinical laboratory. A
      structured questionnaire based on the SERVQUAL service quality model was used for
      data collection, analysis and for the development of the service quality
      framework. FINDINGS: The study confirms the pertinence of the following service
      quality dimensions within the context of clinical laboratories: tangibility,
      reliability, responsiveness, turnaround time, technology, test reports,
      communication and laboratory staff attitude and behaviour. PRACTICAL
      IMPLICATIONS: The service quality framework developed, termed LabSERV, is vital
      for clinical laboratories in the search for improving service delivery to medical
      practitioners. ORIGINALITY/VALUE: This is a pioneering work carried out in the
      clinical laboratory sector in Mauritius. Medical practitioner expectations and
      perceptions have been simultaneously considered to generate a novel service
      quality framework for clinical laboratories.

PMID- 25982638
TI  - Roadmap for developing a national quality indicator set for general practice.
AB  - PURPOSE: The purpose of this paper is to describe a national, comprehensive
      quality indicator set to support delivering high-quality clinical care in Irish
      general practice. DESIGN/METHODOLOGY/APPROACH: Potential general practice quality
      indicators were identified through a literature review. A modified two-stage
      Delphi process was used to rationalise international indicators into an indicator
      set, involving both experts from key stakeholder groups (general practitioners
      (GPs), practice nurses, practice managers, patient and health policy
      representatives) and predominantly randomly selected GPs. An illustrative
      evaluation approach was used to road test the indicator set and supporting
      materials. FINDINGS: In total, 80 panellists completed the two Delphi rounds and
      staff in 13 volunteer practices participated in the road test. The original 171
      indicators was reduced to 147 during the Delphi process and further reduced to 68
      indicators during the road test. The indicators were set out in 14 sub-domains
      across three areas (practice infrastructure, practice processes and procedures,
      and practice staff). Practice staff planned 77 quality improvement activities
      after their assessment against the indicators and 31 (40 per cent) were completed
      with 44 (57 per cent) ongoing and two (3 per cent) not advanced after a six-month
      road test. A General Practice Indicators of Quality indicator set and support
      materials were produced at the conclusion. PRACTICAL IMPLICATIONS: It is
      important and relatively easy to customise existing quality indicators to a
      particular setting. The development process can be used to raise awareness, build
      capacity and drive quality improvement activity in general practices.
      ORIGINALITY/VALUE: The authors describe in detail a method to develop general
      practice quality indicators for a regional or national population from existing
      validated indicators using consensus, action research and an illuminative
      evaluation.

PMID- 25982639
TI  - Clinical pathways in China - an evaluation.
AB  - PURPOSE: Clinical pathways (CPs) are multidisciplinary care plans with essential
      care steps for patients with specific clinical problems. CPs were introduced in
      China in 2009 to assure quality, reduce risks, increase resource efficiency and
      control costs. The purpose of this paper is to present a Chinese public hospital
      case study where a CP pilot was undertaken to evaluate two main outcomes: length
      of stay and hospitalization costs for a tertiary hospital from 2010 to 2012 using
      a mixed-methods approach. DESIGN/METHODOLOGY/APPROACH: Data were drawn from
      hospital records and in-depth interviews with hospital staff in a Shanxi Province
      tertiary hospital, northern China. FINDINGS: The authors found that the main
      objectives: to standardize treatment procedures by reducing length of stay and
      containing costs, were not fully achieved. Staff implementing CPs clearly
      encountered several barriers; i.e., managers did not see the pilot as a useful
      managerial instrument but were still driven by revenue generation. Physicians,
      too, lacked incentive to follow the guidelines due to income concerns. PRACTICAL
      IMPLICATIONS: The authors point to the daunting challenges brought about by
      perverse incentives embedded in the country's health system. The authors argue
      that concerted efforts are needed to undertake difficult health policy reforms in
      China. ORIGINALITY/VALUE: The authors present the first empirical study in the
      English-language literature that examines China's ongoing CP pilots from a micro
      perspective. The authors combine qualitative and quantitative methods and reveal
      the hospital-level dynamics in its implementation.

PMID- 25982640
TI  - An improvement project within urological care.
AB  - PURPOSE: The purpose of this paper is to describe staff experiences in an on
      going improvement project regarding patients with ureteral stones.
      DESIGN/METHODOLOGY/APPROACH: A qualitative descriptive study based on eight group
      interviews and 48 narratives, was performed. Data were analysed using qualitative
      content analysis. Trustworthiness was ensured by using a well-documented
      improvement process method during six months. FINDINGS: The results formed three
      categories: an absent comprehensive view; complexity; and vulnerability within
      the organisation. A holistic perspective regarding urological care at the micro-,
      meso- and macro-levels is needed to improve planning and caring processes.
      RESEARCH LIMITATIONS/IMPLICATIONS: This study includes one team (six members,
      different health professionals) within the same urology department. PRACTICAL
      IMPLICATIONS: Results show that staff need information, such as guidelines and
      support throughout the improvement work to deliver high-quality care. Moreover,
      there is a need for evidence-based guidelines at national level to support
      improvement work. SOCIAL IMPLICATIONS: Healthcare staff need to pay attention to
      all team member needs to improve urological care. Organisational and managerial
      aspect are needed to support clear and common goals regarding healthcare
      improvement work. ORIGINALITY/VALUE: Urological improvement projects, generally,
      are lacking, which is why this study is important to improve nephrolithiasis
      patient care.

PMID- 25982641
TI  - Antimicrobial activity and cytotoxicity of nanofibrous mats immobilized with
      polysaccharides-rectorite based nanogels.
AB  - Rectorite (REC)-encapsulated lysozyme (LY)-alginate (ALG) nanogels (NGs) were
      prepared by adding ALG-REC composites suspensions into LY solutions at the mass
      ratio of 1:2. The morphology of the NGs and the NGs-assembled nanofibrous mats
      were studied by transmission electron microscope and field emission scanning
      electron microscopy, respectively. The composition of NGs-immobilized nanofibrous
      mats was detected by X-ray photoelectron spectroscopy. The NGs-assembled
      nanofibrous mats with the addition of REC could enhance the inhibition against
      Escherichia coli and Staphylococcus aureus. Additionally, NGs-coated mats reduced
      the toxicity of cellulose mats on mouse lung fibroblasts using MTT assay.
      Besides, the addition of REC in the NGs improved the cell compatibility of NGs
      assembled nanofibrous mats. 

PMID- 25982642
TI  - Biochemical, molecular and outcome analysis of eight chinese asymptomatic
      individuals with methyl malonic acidemia detected through newborn screening.
AB  - Methyl malonic academia (MMA) is characterized by abnormal accumulation of methyl
      malonic acid in body fluids. Patients usually have a variety of clinical symptoms
      including recurrent vomiting, metabolic acidosis, developmental delay, seizure,
      or death. However, a few cases where the patients have no symptom are also
      reported. Here, we conducted clinical, biochemical, and molecular analysis of
      eight Chinese patients identified through newborn screening between 2003 and
      2013. All the patients had significantly higher blood propionylcarnitine (C3)
      concentrations, ratio of propionylcarnitine/acetylcarnitine (C3/C2); and their
      urine methyl malonic acid and methylcitric acid (MCA) excretions were remarkably
      higher than normal at diagnosis and during follow-ups. In addition, five
      different known mutations were identified in seven of the eight patients in
      either MUT or MMACHC. All these mutations were expected to produce defective
      proteins that would result in decreased or even total loss of methyl malonyl-CoA
      mutase activity. However, normal outcomes were found in all patients in physical
      growth, intellectual performance and cerebral MRI analysis at diagnosis (range,
      14-53 days) and during follow-ups (range, 1.8-10 years). Our study is the first
      report of Chinese MMA patients with increased secretion of methyl malonic acid
      and molecular defects in MUT or MMACHC yet remain asymptomatic.

PMID- 25982644
TI  - The EAPCI Dual AntiPlatelet Therapy survey: the difficult translation of
      scientific evidence in clinical interventional practice.

PMID- 25982645
TI  - Transcoronary sinus catheter interventions: back in the repertoire?

PMID- 25982646
TI  - EuroIntervention at ten years.

PMID- 25982647
TI  - Mapping interventional cardiology in Europe: proceedings of the 3rd Summit of the
      European Association of Percutaneous Cardiovascular Interventions.

PMID- 25982648
TI  - European expert consensus on rotational atherectomy.
AB  - The interest in rotational atherectomy (RA) has increased over the past decade as
      a consequence of more complex and calcified coronary stenoses being attempted
      with percutaneous coronary interventions. Yet adoption of RA is hampered by
      several factors: amongst others, by the lack of a standardised protocol. This
      European expert consensus document stems from the awareness of the large
      heterogeneity in the protocols adopted to perform rotational atherectomy. The
      objective of the present document is to provide some points of consensus among
      highly experienced operators on the most controversial steps of RA in an attempt
      to build the basis of a standardised and universally accepted protocol. 

PMID- 25982650
TI  - Dual antiplatelet therapy duration after coronary stenting in clinical practice:
      results of an EAPCI survey.
AB  - AIMS: Our aim was to report on a survey initiated by the European Association of
      Percutaneous Cardiovascular Interventions (EAPCI) concerning opinion on the
      evidence relating to dual antiplatelet therapy (DAPT) duration after coronary
      stenting. METHODS AND RESULTS: Results from three randomised clinical trials were
      scheduled to be presented at the American Heart Association Scientific Sessions
      2014 (AHA 2014). A web-based survey was distributed to all individuals registered
      in the EuroIntervention mailing list (n=15,200) both before and after AHA 2014. A
      total of 1,134 physicians responded to the first (i.e., before AHA 2014) and 542
      to the second (i.e., after AHA 2014) survey. The majority of respondents
      interpreted trial results consistent with a substantial equipoise regarding the
      benefits and risks of an extended versus a standard DAPT strategy. Two
      respondents out of ten believed extended DAPT should be implemented in selected
      patients. After AHA 2014, 46.1% of participants expressed uncertainty about the
      available evidence on DAPT duration, and 40.0% the need for clinical guidance.
      CONCLUSIONS: This EAPCI survey highlights considerable uncertainty within the
      medical community with regard to the optimal duration of DAPT after coronary
      stenting in the light of recent reported trial results. Updated recommendations
      for practising physicians to guide treatment decisions in routine clinical
      practice should be provided by international societies.

PMID- 25982649
TI  - Radioprotective lightweight caps in the interventional cardiology setting: a
      randomised controlled trial (PROTECT).
AB  - AIMS: The aim of this study was to test the radioprotection efficacy and comfort
      of newer bilayer barium sulphate-bismuth oxide composite (XPF) caps in an
      interventional cardiology setting. METHODS AND RESULTS: Operators were randomly
      assigned to wear standard fabric (n=59), 0.3 mm (n=74), or 0.5 mm (n=64) lead
      equivalent XPF caps. Radiation doses were measured by using dosimeters placed
      outside and underneath the caps. Wearing comfort was assessed at the end of each
      measurement on a visual analogue scale (VAS) (0-100, with 100 indicating optimal
      comfort). Procedural data did not differ between the XPF and standard groups.
      Mean standard, XPF 0.3 mm, and XPF 0.5 mm cap weights were 12.5 g, 118.4 g, and
      123.7 g, respectively. VAS comfort ratings of the standard and XPF caps did not
      differ significantly (p=0.272). The mean radiation protection was 12.0%, 95% CI:
      4.9-19.1% (standard caps, n=35), 91.5%, 95% CI: 87.4-95.6% (XPF 0.3 mm caps,
      n=45) and 97.1%, 95% CI: 92.5-100% (XPF 0.5 mm caps, n=44) (p<=0.001 for all
      group comparisons). Using the XPF caps, a cumulative total radiation dose
      reduction by almost factor 10 was evident (272 procedures, 22,310 MUSv outside
      the XPF caps, 2,770 MUSv inside the caps). CONCLUSIONS: Lightweight XPF caps show
      comparable comfort to standard fabric caps, but provide substantial radiation
      protection during fluoroscopy-guided cardiac interventions.

PMID- 25982651
TI  - Intravascular ultrasound evaluation of JETSTREAM atherectomy removal of
      superficial calcium in peripheral arteries.
AB  - AIMS: Endovascular treatment of calcified femoral-popliteal disease is
      challenging. We sought to evaluate the mechanism of lumen gain when using the
      JETSTREAM Atherectomy System to treat calcified peripheral artery lesions.
      METHODS AND RESULTS: The JETSTREAM Calcium Study was a prospective, single-arm,
      multicentre study to evaluate the JETSTREAM Atherectomy System for severely
      calcified femoral-popliteal artery lesions, i.e., patients with claudication and
      lesions with superficial calcium >90 degrees  and >5 mm in length as determined
      by intravascular ultrasound (IVUS). The 2.1 mm catheter was used in this study
      without distal protection. Fifty-five patients underwent angiographic screening:
      26 (45%) met IVUS inclusion criteria. Angiographic calcium was moderate in eight
      cases and severe in 14, with no available data for four cases. Visual diameter
      stenosis was 86+/-9% pre-treatment, 37+/-13% post atherectomy, and 10+/-6% post
      adjunctive treatment (adjunctive PTA+stenting in eight and adjunct PTA alone in
      16). IVUS showed lumen area increased from 6.6+/-3.7 mm2 to 10.0+/-3.6 mm2
      (p=0.001): calcium reduction was responsible for 86+/-23% of the lumen increase.
      Although the superficial calcium arc did not change (151+/-70 degrees  to 146+/
      71 degrees , p=0.83), the arc of reverberation increased (23+/-20 degrees  to
      65+/-40 degrees , p=0.006), indicating device-related modification of calcium.
      Adjunctive balloon angioplasty was performed in 62% of the lesions, and stent
      implantation in 31%. In 11 cases with adjunctive balloon dilation, the MLA
      increased from 7.1 (6.4, 7.8) mm2 post atherectomy to 11.9 (10.3, 13.5) mm2 post
      balloon (p<0.001) without flow-limiting dissection. No major adverse events
      occurred up to 30 days post procedure in either the study group or the patients
      who were excluded from the analysis. CONCLUSIONS: The JETSTREAM Atherectomy
      System increased lumen dimensions in moderately or severely calcified femoral
      popliteal lesions by removing superficial calcium without major complications.

PMID- 25982652
TI  - Symplicity multi-electrode radiofrequency renal denervation system feasibility
      study.
AB  - AIMS: The aim of this study was to test the safety and performance of the
      SymplicityTM multi-electrode radio-frequency renal denervation system which was
      designed to reduce procedure time during renal denervation. METHODS AND RESULTS:
      The multi-electrode radiofrequency renal denervation system feasibility study is
      a prospective, non-randomised, open label, feasibility study that enrolled 50
      subjects with hypertension. The study utilises a new renal denervation catheter
      which contains an array of four electrodes mounted in a helical configuration at
      90 degrees from each other to deliver radiofrequency energy simultaneously to all
      four renal artery quadrants for 60 seconds. The protocol specified one renal
      denervation treatment towards the distal end of each main renal artery with
      radiofrequency energy delivered for 60 seconds per treatment. Total treatment
      time for both renal arteries was two minutes. The 12-month change in office
      systolic blood pressure (SBP) and 24-hour SBP was -19.2+/-25.2 mmHg, p<0.001, and
      -7.6+/-20.0 mmHg, p=0.020, respectively. There were three patients with access
      site complications, none of which was related to energy delivery; all were
      treated successfully. No new renal artery stenosis or hypertensive emergencies
      occurred. CONCLUSIONS: The Symplicity multi-electrode radiofrequency renal
      denervation system was associated with a significant reduction in SBP at 12
      months and minimal complications whilst it also reduced procedure time. TRIAL
      REGISTRATION: NCT01699529.

PMID- 25982653
TI  - Central pulse pressure predicts BP reduction after renal denervation in patients
      with treatment-resistant hypertension.
AB  - AIMS: Enhanced vascular ageing is associated with elevated central pulse pressure
      (cPP), an independent predictor of cardiovascular (CV) events. Although
      antihypertensive treatment strategies are effective, high residual CV risk
      remains indicative of advanced and largely irreversible vascular damage. Renal
      denervation (RDN) has been shown to reduce blood pressure (BP) to various extents
      in patients with treatment-resistant hypertension (TRH). We hypothesised that cPP
      predicts BP reduction after RDN. METHODS AND RESULTS: Sixty-three patients with
      true TRH underwent catheter-based RDN using the Symplicity FlexTM catheter and
      were followed for six months. At baseline, cPP was assessed by pulse wave
      analysis (SphygmoCorTM). Patients were stratified according to their median cPP
      (55 mmHg), and called "low cPP" (below the median) or "high cPP" (above the
      median). Office BP reduction six months after RDN was greater (-22+/-19/-13+/-11
      vs. -12+/-20/-5+/-13 mmHg, p=0.038/0.014) and 24-hr ambulatory blood pressure
      (ABP) reduction tended to be greater (-11+/-13/-8+/-10 vs. -3+/-18/-4+/-10 mmHg,
      p=0.070/0.112) in patients with low cPP compared to those with high cPP. Only cPP
      (beta=0.687, p=0.001) and baseline systolic BP (beta=-0.564, p<0.001) were
      independent determinants of office systolic BP reduction after RDN. CONCLUSIONS:
      Our data suggest that cPP, indicative of the degree of large arterial stiffening,
      may be helpful to identify responders to RDN.

PMID- 25982654
TI  - Initial experience with therapeutic geometric modification of the carotid bulb
      for true resistant hypertension.
AB  - The contribution of carotid baroreceptor feedback in preventing or potentially
      contributing to the essential hypertensive cascade is poorly understood. It is
      clear the carotid sinus nerve action potentials are triggered by carotid bulb
      stretch rather than pressure and are only sustained during pulsatile increases in
      pressure. In addition, the carotid baroreceptor negative feedback is gradually
      extinguished in hypertension patients (a phenomenon known as "resetting"). We
      report a case of significant reduction in blood pressure in a patient with true
      resistant hypertension after change in the carotid bulb pulsatile strain patterns
      following the implant of an intravascular prosthesis. 

PMID- 25982655
TI  - Transcatheter creation of a reverse Potts shunt in a patient with severe
      pulmonary arterial hypertension associated with Moyamoya syndrome.

PMID- 25982656
TI  - Novel approaches to composite endpoints in clinical trials.

PMID- 25982657
TI  - How should I treat a patient with refractory angina and a single stenosis with
      normal FFR but abnormal CFR?

PMID- 25982658
TI  - Cognitive activity, cognitive function, and brain diffusion characteristics in
      old age.
AB  - The objective of this work was to test the hypotheses that a) more frequent
      cognitive activity in late life is associated with higher brain diffusion
      anisotropy and lower trace of the diffusion tensor, and b) brain diffusion
      characteristics partially mediate the association of late life cognitive activity
      with cognition. As part of a longitudinal cohort study, 379 older people without
      dementia rated their frequency of participation in cognitive activities,
      completed a battery of cognitive function tests, and underwent diffusion tensor
      imaging. We used tract-based spatial statistics to test the association between
      late life cognitive activity and brain diffusion characteristics. Clusters with
      statistically significant findings defined regions of interest in which we tested
      the hypothesis that diffusion characteristics partially mediate the association
      of late life cognitive activity with cognition. More frequent cognitive activity
      in late life was associated with higher level of global cognition after
      adjustment for age, sex, education, and indicators of early life cognitive
      enrichment (p = 0.001). More frequent cognitive activity was also related to
      higher fractional anisotropy in the left superior and inferior longitudinal
      fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p <
      0.05, FWE-corrected). After controlling for fractional anisotropy or trace from
      these regions, the regression coefficient for the association of late life
      cognitive activity with cognition was reduced by as much as 26 %. These findings
      suggest that the association of late life cognitive activity with cognition may
      be partially mediated by brain diffusion characteristics.

PMID- 25982661
TI  - Alcohol use disorders: tracts, twins, and trajectories.

PMID- 25982660
TI  - Brain development in heavy-drinking adolescents.
AB  - OBJECTIVE: Heavy alcohol use during adolescence may alter the trajectory of
      normal brain development. The authors measured within-subject changes in regional
      brain morphometry over longer intervals and in larger samples of adolescents than
      previously reported and assessed differences between adolescents who remained
      nondrinkers and those who drank heavily during adolescence as well as differences
      between the sexes. METHOD: The authors examined gray and white matter volume
      trajectories in 134 adolescents, of whom 75 transitioned to heavy drinking and 59
      remained light drinkers or nondrinkers over roughly 3.5 years. Each underwent MRI
      scanning two to six times between ages 12 and 24 and was followed for up to 8
      years. The volumes of the neocortex, allocortex, and white matter structures were
      measured using atlas-based parcellation with longitudinal registration. Linear
      mixed-effects models described differences in trajectories of heavy drinkers and
      nondrinkers over age; secondary analyses considered the contribution of other
      drug use to identified alcohol use effects. RESULTS: Heavy-drinking adolescents
      showed accelerated gray matter reduction in cortical lateral frontal and temporal
      volumes and attenuated white matter growth of the corpus callosum and pons
      relative to nondrinkers. These results were largely unchanged when use of
      marijuana and other drugs was examined. Male and female drinkers showed similar
      patterns of development trajectory abnormalities. CONCLUSIONS: Longitudinal
      analysis enabled detection of accelerated typical volume decline in frontal and
      temporal cortical volumes and attenuated growth in principal white matter
      structures in adolescents who started to drink heavily. These results provide a
      call for caution regarding heavy alcohol use during adolescence, whether heavy
      drinking is the sole cause or one of several in these alterations in brain
      development.

PMID- 25982662
TI  - Elucidating the relationship between superoxide anion levels and lifespan using
      an enhanced two-photon fluorescence imaging probe.
AB  - We report a new reversible fluorescent two-photon (TP) probe (PY-CA) with high TP
      absorption cross section and pH-independent fluorescence response, which allow
      monitoring of O2(-) fluxes dynamically, selectively and sensitively. The imaging
      results indicate that O2(-) at high levels can shorten the life of Caenorhabditis
      elegans. 

PMID- 25982663
TI  - An assessment of fiscal space for health in Bhutan.
AB  - Several factors are expected to put a strain on health financing in Bhutan. In a
      predominantly public-financed healthcare, ensuring that the health system gains
      sufficient fiscal space to ensure the sustainability of its financing is a
      critical policy concern. This fiscal space assessment bases its analysis on
      national surveys and statistics, international databases and review of official
      documents and reports. Assuming that the government health spending will continue
      to respond in the same way to growth as in the period 2002-2012, Bhutan can
      expect to see a robust increase in government investments in health. If
      elasticity of health expenditure with respect to GDP does not change
      significantly, projections indicate that per-capita government spending for
      health could more than double in the period 2012 to 2019. This increase from
      Ngultrum 2632 in 2012 to Ngultrum 6724 in 2019 could correspond to government
      health spending from 2.65% of GDP to 3.98% of GDP in the respective years. The
      country, however, needs to closely monitor and ensure that government investment
      in healthcare keeps pace with the growth of the national economy. Along with
      this, supplementary resources for healthcare could be explored through earmarked
      taxes and by generating efficiency gains. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 25982659
TI  - Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain
      Activity During Behavioral Control in a Genome-Wide Methylation Analysis.
AB  - OBJECTIVE: The genetic component of alcohol use disorder is substantial, but
      monozygotic twin discordance indicates a role for nonheritable differences that
      could be mediated by epigenetics. Despite growing evidence associating
      epigenetics and psychiatric disorders, it is unclear how epigenetics,
      particularly DNA methylation, relate to brain function and behavior, including
      drinking behavior. METHOD: The authors carried out a genome-wide analysis of DNA
      methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and
      validated differentially methylated regions. After validation, the authors
      characterized these differentially methylated regions using personality trait
      assessment and functional MRI in a sample of 499 adolescents. RESULTS:
      Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was
      associated with alcohol use disorder. The authors found association of PPM1G
      hypermethylation with early escalation of alcohol use and increased
      impulsiveness. They also observed association of PPM1G hypermethylation with
      increased blood-oxygen-level-dependent response in the right subthalamic nucleus
      during an impulsiveness task. CONCLUSIONS: Overall, the authors provide first
      evidence for an epigenetic marker associated with alcohol consumption and its
      underlying neurobehavioral phenotype.

PMID- 25982664
TI  - A Phytochemical-Halogenated Quinoline Combination Therapy Strategy for the
      Treatment of Pathogenic Bacteria.
AB  - With the continued rise of drug-resistant bacterial infections coupled with the
      current discouraging state of the antibiotic pipeline, the need for new
      antibacterial agents that operate through unique mechanisms compared with
      conventional antibiotics and work in synergy with other agents is at an all-time
      high. We have discovered that gallic acid, a plant-derived phytochemical,
      dramatically potentiates the antibacterial activities of several halogenated
      quinolines (up to 11,800-fold potentiation against Staphylococcus aureus) against
      pathogenic bacteria, including drug-resistant clinical isolates. S. aureus
      demonstrated the highest sensitivity towards gallic acid-halogenated quinoline
      combinations, including one halogenated quinoline that demonstrated potentiation
      of biofilm eradication activity against a methicillin-resistant S. aureus (MRSA)
      clinical isolate. During our studies, we also demonstrated that these halogenated
      quionlines operate through an interesting metal(II) cation-dependent mechanism
      and display promising mammalian cytotoxicity.

PMID- 25982665
TI  - Sporadic Gastric Hyperplastic Polyposis with Superimposed Multifocal
      Adenocarcinoma, an Extremely Rare Case Report and Review of the Literature.

PMID- 25982666
TI  - Plasma heat shock protein 27 is increased in renal dysfunction and habitual
      smoking in a Japanese general population.
AB  - BACKGROUND: Heat shock proteins (HSPs) work as "chaperones" to affect protein
      folding of newly synthesized or denatured proteins. HSP 27 plays an important
      role in coronary artery disease or renal disease as the result of oxidative
      stress. Although habitual smoking is well known to induce oxidative stress, there
      is no epidemiological evidence between plasma HSP 27 and renal dysfunction or
      smoking habits. METHODS: A total of 451 residents (167 men and 284 women, age
      65.7 years) underwent a history and physical examination, and determination of
      blood chemistries, including plasma levels of HSP 27. HSP 27 levels were measured
      by using enzyme-linked immunosorbent assay kits. RESULTS: Elevated HSP 27 levels
      were independently associated with estimated glomerular filtration rate (eGFR)
      (p<0.001) and smoking habits (p<0.05). HSP 27 levels were significantly decreased
      stratified by groups of eGFR (p<0.001 for trend) by analysis of co-variance
      (ANCOVA) adjusted for age, sex, and smoking habits. HSP 27 levels were increased
      with more smoking of cigarettes. In particular, HSP 27 levels were increased in
      the heavy smokers (>=20cigarettes/day) by ANCOVA adjusted for age, sex, and eGFR
      compared with non-smokers and light smokers (p<0.05 for trend). CONCLUSIONS: The
      present study demonstrated that HSP 27 levels were strongly related to renal
      dysfunction and habitual smoking in a dose-response manner in a Japanese general
      population.

PMID- 25982667
TI  - Major cardiac event risk scores estimated with gated myocardial perfusion imaging
      in Japanese patients with coronary artery disease.
AB  - BACKGROUND: A Heart Risk Table has been reported as the first risk score based on
      nuclear cardiology to predict cardiac event rates in Japanese patients. However,
      there are no risk scores estimating risk of major cardiac events (MCEs) except
      severe heart failure. METHODS: We retrospectively investigated 2579 patients with
      known or suspected coronary artery disease (CAD) who underwent rest (201)Tl and
      stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed
      tomography between October 2004 and March 2011 and who had data on a 3-year
      follow-up. The perfusion images were analyzed with 20 segments of a five-point
      visual scoring model to estimate summed defect scores. The endpoint was the onset
      of MCEs consisting of cardiac death, non-fatal myocardial infarction and unstable
      angina pectoris. RESULTS: During the 3-year follow-up, 171 patients (6.6%)
      experienced MCEs comprising cardiac death (n=78), non-fatal myocardial infarction
      (n=30), and unstable angina pectoris (n=63). The multivariate logistic regression
      analysis indicated age, diabetes, estimated glomerular filtration rate (eGFR),
      and summed stress scores (SSS) as independent predictors of the MCEs and age,
      stress ejection fraction, eGFR, and SSS as independent predictors of cardiac
      death. Those four predictors and coefficients corresponding to them were used to
      make two different risk equations: MCE risk (%/3 years)=1/{1+Exp[-(
      3.176+0.018*age+0.602*diabetes-0.022*eGFR+0.051*SSS)]}*100 and cardiac death risk
      (%/3 years)=1/{1+Exp[-(-2.602+0.031*age-0.031*eGFR+0.038*SSS-0.029*stress
      ejection fraction)]}*100. CONCLUSION: The risk scores obtained from this study
      are useful to predict MCEs in Japanese patients with CAD and are expected to be
      useful for management and informed consent of high-risk CAD patients.

PMID- 25982668
TI  - Clinical outcomes of the intra-aortic balloon pump for resuscitated patients with
      acute myocardial infarction complicated by cardiac arrest.
AB  - BACKGROUND: The aim of this study was to investigate the clinical effects of
      intra-aortic balloon pump (IABP) in patients who received cardiopulmonary
      resuscitation (CPR) before procedure. METHODS AND RESULTS: Between November 2005
      and April 2014, 49,542 patients were enrolled in a prospective cohort study for
      acute myocardial infarction (AMI) in Korea (KAMIR). CPR was performed in 1700
      patients with cardiac arrest. Patients were excluded from the study if they had
      not undergone a coronary angiogram, if extracorporeal membrane oxygenation or
      thrombolysis was performed, and if mechanical complications presented. The
      primary end point was 1-month all-cause mortality. A total of 883 patients in the
      IABP group and 476 in the control group were included. During the 1-month follow
      up, all-cause death occurred in 749 patients (55.1%). The IABP group was
      predominantly male and had a higher prevalence of ST-segment elevation MI and a
      higher risk of coronary lesions including left main disease and three-vessel
      disease. Glycoprotein IIb/IIIa inhibitor was administered less in the non-IABP
      group. In the total population, the IABP group had worse outcomes in terms of
      mortality rates after multivariate analysis [hazard ratio (HR) 1.22, 95%
      confidence interval (CI) 1.02-1.47, p=0.034] without increasing the incidence of
      recurrent MI, stroke, and major bleeding. After propensity matching with a pair
      of 452 patients, no significant differences were observed in baseline
      characteristics or clinical outcomes (HR 1.21, 95% CI 0.93-1.57, p=0.158).
      CONCLUSION: The use of IABP did not show clinical benefits in patients with AMI
      complicated by severe cardiogenic shock after propensity matching analysis.

PMID- 25982669
TI  - Evaluation of the safety and efficacy of TY-51924 in patients with ST elevated
      acute myocardial infarction - Early phase II first in patient pilot study.
AB  - BACKGROUND: In myocardial ischemia-reperfusion injuries, the involvement of the
      Na(+)/H(+) exchanger (NHE) is considered to be one of the pathogenic mechanisms
      following reperfusion. TY-51924 is a novel hydrophilic NHE inhibitor with a lower
      risk of central neurotoxicity than previous NHE inhibitors. This open-label, dose
      escalating study was undertaken to investigate the safety, efficacy, and
      pharmacokinetics of TY-51924 in patients with ST-elevation myocardial infarction
      (STEMI). METHODS: Consent was obtained from a total of 30 patients with first
      anterior STEMI. After 12 patients were determined to be ineligible, the remaining
      18 patients, each of whom was undergoing primary percutaneous coronary
      intervention (pPCI), received TY-51924 intravenously up to 10, 20, or 30mg/kg as
      the low-, medium-, or high-dose groups, respectively (n=6 in each group). The
      primary endpoints were safety (up to 7 days) and plasma drug concentration. The
      myocardial salvage index (MSI) was measured by (201)Tl/(123)I-beta-methyl-p
      iodophenyl pentadecanoic acid single photon emission computed tomography (SPECT)
      3-5 days after pPCI. RESULTS: No side effects were observed. Plasma drug
      concentrations increased dose-dependently, and were subsequently eliminated
      rapidly. MSIs were 0.118, 0.335, and 0.192 in the low-, medium-, and high-dose
      groups, respectively. In additional analysis, the combined MSIs in the medium-
      and high-dose groups were significantly higher than those in the low-dose group,
      in patients with a longer time from symptom onset to reperfusion (p=0.0247).
      CONCLUSIONS: No side effects were observed even at the highest dose with this
      novel hydrophilic NHE inhibitor. Therefore, TY-51924 is thought to be safe in
      patients with STEMI, even at the highest dose. Potential cardioprotective effects
      of intravenous TY-51924 might be expected based on the results obtained for the
      MSIs using SPECT at 20-30mg/kg. However, further large-scale, double-blind,
      placebo-controlled clinical studies are required to confirm the efficacy and
      safety implied in the current study.

PMID- 25982670
TI  - Low left atrial appendage flow velocity predicts recurrence of atrial
      fibrillation after catheter ablation of persistent atrial fibrillation.
AB  - BACKGROUND: Recurrence after catheter ablation of persistent atrial fibrillation
      (AF) remains an unsolved issue. This study aimed to explore the association
      between the left atrial appendage peak flow velocity (LAAV) and AF recurrence
      after ablation in persistent AF patients. METHODS: Fifty-three consecutive
      patients who underwent an initial catheter ablation of persistent AF were
      enrolled [age, 65+/-10 years; male, 42 (79%)]. The LAAV was obtained by
      transesophageal echocardiography before ablation. All the patients underwent
      pulmonary vein isolation and were followed up for 12 months. The LAAV and other
      clinical factors (AF duration, CHA2DS2VASc score, left atrial diameter, left
      atrial volume, and left ventricular ejection fraction) were tested using a Cox
      proportional hazards regression analysis as predictors of AF recurrence during
      the 1-year follow-up. RESULTS: AF recurrence occurred in 16 (30%) patients. The
      patients with AF recurrences had lower LAAVs (23.3+/-7.2cm/s vs. 33.3+/-15.1cm/s,
      p=0.002) than those without AF recurrence. In the multivariable analysis, a low
      LAAV independently predicted AF recurrence (hazard ratio, 3.04; 95% confidence
      interval, 1.05-8.79; p=0.040). A Kaplan-Meier analysis also demonstrated a lower
      survival rate free from AF recurrence in the low LAAV group than in the high LAAV
      group (p=0.030). CONCLUSION: A low LAAV was associated with AF recurrence after
      the initial catheter ablation of persistent AF.

PMID- 25982671
TI  - Thyroid function on admission and outcome in patients hospitalized for acute
      decompensated heart failure.
AB  - BACKGROUND: Although thyroid dysfunction is a known prognostic factor for
      cardiovascular disease, the relationship between thyroid function and prognosis
      in patients with acute decompensated heart failure (ADHF) is poorly understood.
      Herein, we investigated the association between thyroid hormone levels and
      outcome in patients hospitalized for ADHF. METHODS: We evaluated 270 hospitalized
      ADHF patients with thyroid hormone levels measured at admission between April
      2007 and May 2012. RESULTS: The median (interquartile range) thyroid stimulating
      hormone, free triiodothyronine (fT3), and free thyroxine were 2.79 (1.49
      4.96)MUU/ml, 2.32 (1.93-2.75)pg/ml, and 14.0 (12.1-15.7)pg/dl, respectively.
      Receiver operating characteristic (ROC) curve analysis was applied to assess
      their prognostic value for in-hospital outcome. The fT3 had the most favorable
      performance, with an area under the ROC curve of 0.791 (optimal cutoff point
      <=2.05; sensitivity 85.0%; specificity 72.0%). Although patients in the low fT3
      group (<=2.05) had higher age and lower body mass index, there were no
      significant differences with respect to systolic blood pressure and heart rate
      between the groups. In multivariate analysis adjusted for various markers of
      disease severity and amiodarone use, low fT3 level was independently associated
      with higher in-hospital mortality (odds ratio 14.4; p<0.001). In addition, the
      probability of 1-year total death among patients with low fT3 was significantly
      higher than that among patients with normal fT3 (log-rank p<0.001). CONCLUSIONS:
      Low fT3 level was associated with adverse outcomes in patients hospitalized for
      ADHF. Thyroid hormone measurements might be useful in the risk stratification of
      ADHF patients.

PMID- 25982672
TI  - Highly reproductive Escherichia coli cells with no specific assignment to the UAG
      codon.
AB  - Escherichia coli is a widely used host organism for recombinant technology, and
      the bacterial incorporation of non-natural amino acids promises the efficient
      synthesis of proteins with novel structures and properties. In the present study,
      we developed E. coli strains in which the UAG codon was reserved for non-natural
      amino acids, without compromising the reproductive strength of the host cells.
      Ninety-five of the 273 UAG stop codons were replaced synonymously in the genome
      of E. coli BL21(DE3), by exploiting the oligonucleotide-mediated base-mismatch
      repair mechanism. This genomic modification allowed the safe elimination of the
      UAG-recognizing cellular component (RF-1), thus leaving the remaining 178 UAG
      codons with no specific molecule recognizing them. The resulting strain B
      95.DeltaA grew as vigorously as BL21(DE3) in rich medium at 25-42 degrees C, and
      its derivative B-95.DeltaADeltafabR was better adapted to low temperatures and
      minimal media than B-95.DeltaA. UAG was reassigned to synthetic amino acids by
      expressing the specific pairs of UAG-reading tRNA and aminoacyl-tRNA synthetase.
      Due to the preserved growth vigor, the B-95.DeltaA strains showed superior
      productivities for hirudin molecules sulfonated on a particular tyrosine residue,
      and the Fab fragments of Herceptin containing multiple azido groups.

PMID- 25982673
TI  - Sarcomeres Pattern Proprioceptive Sensory Dendritic Endings through UNC
      52/Perlecan in C. elegans.
AB  - Sensory dendrites innervate peripheral tissues through cell-cell interactions
      that are poorly understood. The proprioceptive neuron PVD in C. elegans extends
      regular terminal dendritic branches between muscle and hypodermis. We found that
      the PVD branch pattern was instructed by adhesion molecule SAX-7/L1CAM, which
      formed regularly spaced stripes on the hypodermal cell. The regularity of the SAX
      7 pattern originated from the repeated and regularly spaced dense body of the
      sarcomeres in the muscle. The extracellular proteoglycan UNC-52/Perlecan linked
      the dense body to the hemidesmosome on the hypodermal cells, which in turn
      instructed the SAX-7 stripes and PVD dendrites. Both UNC-52 and hemidesmosome
      components exhibited highly regular stripes that interdigitated with the SAX-7
      stripe and PVD dendrites, reflecting the striking precision of subcellular
      patterning between muscle, hypodermis, and dendrites. Hence, the muscular
      contractile apparatus provides the instructive cues to pattern proprioceptive
      dendrites. 

PMID- 25982674
TI  - Decrease in Cell Volume Generates Contractile Forces Driving Dorsal Closure.
AB  - Biological tissues must generate forces to shape organs and achieve proper
      development. Such forces often result from the contraction of an apical acto
      myosin meshwork. Here we describe an alternative mechanism for tissue
      contraction, based on individual cell volume change. We show that during
      Drosophila dorsal closure (DC), a wound healing-related process, the contraction
      of the amnioserosa (AS) is associated with a major reduction of the volume of its
      cells, triggered by caspase activation at the onset of the apoptotic program of
      AS cells. Cell volume decrease results in a contractile force that promotes
      tissue shrinkage. Estimating mechanical tensions with laser dissection and using
      3D biophysical modeling, we show that the cell volume decrease acts together with
      the contraction of the actin cable surrounding the tissue to govern DC kinetics.
      Our study identifies a mechanism by which tissues generate forces and movements
      by modulating individual cell volume during development. 

PMID- 25982675
TI  - BK Channels Alleviate Lysosomal Storage Diseases by Providing Positive Feedback
      Regulation of Lysosomal Ca2+ Release.
AB  - Promoting lysosomal trafficking represents a promising therapeutic approach for
      lysosome storage diseases. Efficient Ca(2+) mobilization from lysosomes is
      important for lysosomal trafficking. Ca(2+) release from lysosomes could generate
      a negative potential in the lumen to disturb subsequent Ca(2+) release in the
      absence of counter ion flux. Here we report that lysosomes express big
      conductance Ca(2+)-activated potassium (BK) channels that form physical and
      functional coupling with the lysosomal Ca(2+) release channel, TRPML1. Ca(2+)
      release via TRPML1 causes BK activation, which in turn facilitates further
      lysosomal Ca(2+) release and membrane trafficking. Importantly, BK overexpression
      rescues the impaired TRPML1-mediated Ca(2+) release and abnormal lysosomal
      storage in cells from Niemann-Pick C1 patients. Therefore, we have identified a
      lysosomal K(+) channel that provides a positive feedback mechanism to facilitate
      TRPML1-mediated Ca(2+) release and membrane trafficking. Our findings suggest
      that upregulating BK may be a potential therapeutic strategy for certain
      lysosomal storage diseases and common neurodegenerative disorders. 

PMID- 25982676
TI  - The Triple-Repeat Protein Anakonda Controls Epithelial Tricellular Junction
      Formation in Drosophila.
AB  - In epithelia, specialized tricellular junctions (TCJs) mediate cell contacts at
      three-cell vertices. TCJs are fundamental to epithelial biology and disease, but
      only a few TCJ components are known, and how they assemble at tricellular
      vertices is not understood. Here we describe a transmembrane protein, Anakonda
      (Aka), which localizes to TCJs and is essential for the formation of tricellular,
      but not bicellular, junctions in Drosophila. Loss of Aka causes epithelial
      barrier defects associated with irregular TCJ structure and geometry, suggesting
      that Aka organizes cell corners. Aka is necessary and sufficient for accumulation
      of Gliotactin at TCJs, suggesting that Aka initiates TCJ assembly by recruiting
      other proteins to tricellular vertices. Aka's extracellular domain has an unusual
      tripartite repeat structure that may mediate self-assembly, directed by the
      geometry of tricellular vertices. Conversely, Aka's cytoplasmic tail is
      dispensable for TCJ localization. Thus, extracellular interactions, rather than
      TCJ-directed intracellular transport, appear to mediate TCJ assembly. 

PMID- 25982677
TI  - Diabetic foot ulcer--A review on pathophysiology, classification and microbial
      etiology.
AB  - As the prevalence of diabetes is increasing globally, secondary complications
      associated to this endocrinal disorder are also ascending. Diabetic foot ulcers
      are potentially modifying complications. Disruption of harmony in glucose
      homeostasis causes hyperglycemic status, results in activation of certain
      metabolic pathways which in their abnormal state subsequently leads to
      development of vascular insufficiency, nerve damages headed by ulceration in
      lower extremity due to plantar pressures and foot deformity. Insult to foot
      caused by trauma at the affected site goes unnoticeable to patient due to loss of
      sensation. Among the above mention causes, resistance to infection is also
      considered as chief modulator of pathophysiological image of diabetic foot
      lesions. Healing as well as non-healing nature of ulcer relies upon the wound
      microbial communities and the extent of their pathogenicity. A validated
      classification system of foot ulcer is primarily necessary for clinicians in
      management of diabetic foot problems. Another aspect which needs management is
      proper identification of causative pathogen causing infection. The way of
      approaches presently employed in the diagnosis for treatment of foot ulcer
      colonized by different microbes is conventional techniques. Conventional
      diagnostic methods are widely acceptable since decades. But in recent years newly
      invented molecular techniques are exploring the use of 16S ribosomal regions
      specific to prokaryotes in bacterial identification and quantification. Molecular
      techniques would be a better choice if engaged, in finding the specific species
      harboring the wound. 

PMID- 25982678
TI  - The impact of thiamine supplementation on blood pressure, serum lipids and C
      reactive protein in individuals with hyperglycemia: a randomised, double-blind
      cross-over trial.
AB  - BACKGROUND: The adverse effects of hyperglycemia may be potentiated when it is
      accompanied with hypertension and dyslipidemia. This study assessed the effects
      of high dose thiamine on blood pressure, serum lipids and C-reactive protein (hs
      CRP) in individuals with impaired glucose metabolism. METHODS: This was a double
      blind, randomised trial, where 12 hyperglycemic subjects (10 cases of impaired
      glucose tolerance and 2 new cases of type 2 diabetes mellitus) received both
      placebo and thiamine capsules (3 * 100 mg/day) for six weeks in a cross-over
      manner. Anthropometric measurements, systolic and diastolic blood pressure (SBP &
      DBP), serum cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, hs-CRP
      and thiamine status were evaluated at the start, after three weeks and on the
      completion of each arm. RESULTS: DBP was significantly decreased in participants
      consuming thiamine supplements for six weeks (67.9 +/- 5.8 mm Hg) relative to
      baseline (71.4 +/- 7.4 mm Hg, p=0.005) and week 3 (70.9. +/- 5.8 mm Hg, p=0.02).
      This was accompanied with a tendency toward a lower SBP at week six relative to
      baseline (116.5 +/- 11.0 vs. 120.7 +/- 15.3 mm Hg, p=0.06). Also, mean arterial
      pressure (MAP) determined in the supplement arm after six weeks was significantly
      lower than baseline (84.1 +/- 6.5 vs. 87.8 +/- 9.0, p=0.005). These variables did
      not change in the placebo arm. No significant change was detected in the
      supplement or placebo arms when lipid profile and hs-CRP were assessed.
      CONCLUSION/INTERPRETATION: High dose thiamine supplementation may have beneficial
      effects on the blood pressure of individuals with hyperglycemia at early stages,
      and may have a role in the prevention of further vascular complications. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12611000051943.

PMID- 25982679
TI  - Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment
      of glioblastoma.
AB  - Glioblastoma is the most frequent primary malignant brain tumor in adults.
      Despite treatments including surgery, radiotherapy and chemotherapy by oral
      Temozolomide (TMZ), the prognosis of patients with glioblastoma remains very
      poor. We hypothesized that a polyethylene glycol dimethacrylate (PEG-DMA)
      injectable hydrogel would provide a sustained and local delivery of TMZ. The
      hydrogel photopolymerized rapidly (<2min) and presented a viscous modulus
      (~10kPa). TMZ release kinetic presented two phases: a linear burst release of 45%
      of TMZ during the first 24h, followed by a logarithmic release of 20% over the
      first week. The in vivo tolerability study showed that the unloaded hydrogel did
      not induce apoptosis in mice brains nor increased microglial activation. In vivo,
      the anti-tumor efficacy of TMZ-hydrogel was evaluated on xenograft U87MG tumor
      bearing nude mice. The tumor weight of mice treated with the photopolymerized TMZ
      hydrogel drastically decreased compared with all other groups. Higher apoptosis
      (located at the center of the tumor) was also observed. The present study
      demonstrates the potential of a photopolymerizable TMZ-loaded hydrogel to treat
      glioblastoma. 

PMID- 25982680
TI  - Development of a gene-activated scaffold platform for tissue engineering
      applications using chitosan-pDNA nanoparticles on collagen-based scaffolds.
AB  - Biomaterial scaffolds that support cell infiltration and tissue formation can
      also function as platforms for the delivery of therapeutics such as drugs,
      proteins, and genes. As burst release of supraphysiological quantities of
      recombinant proteins can result in adverse side effects, the objective of this
      study was to explore the potential of a series of collagen-based scaffolds,
      developed in our laboratory, as gene-activated scaffold platforms with potential
      in a range of tissue engineering applications. The potential of chitosan, a
      biocompatible material derived from the shells of crustaceans, as a gene delivery
      vector was assessed using mesenchymal stem cells (MSCs). A transfection
      efficiency of >45% is reported which is similar to what is achieved with
      polyethyleneimine (PEI), a non-viral gold standard vector, without causing
      cytotoxic side effects. When the optimised chitosan nanoparticles were
      incorporated into a series of collagen-based scaffolds, sustained transgene
      expression from MSCs seeded on the scaffolds was maintained for up to 28days and
      interestingly the composition of the scaffold had an effect on transfection
      efficiency. These results demonstrate that by simply varying the scaffold
      composition and the gene (or combinations thereof) chosen; the system has
      potential for a myriad of therapeutic applications. 

PMID- 25982681
TI  - Nuclear localization of MUC1 extracellular domain in breast, head and neck, and
      colon cancer.
AB  - BACKGROUND: The glycoprotein MUC1 is overexpressed and underglycosylated in
      cancer cells. MUC1 is translated as a single polypeptide that undergoes
      autocleavage into 2 subunits (the extracellular domain and the cytoplasmic tail),
      and forms a stable heterodimer at the apical membrane of normal epithelial cells.
      The MUC1 cytoplasmic tail localizes to the cytoplasm of transformed cells and is
      targeted to the nucleus. AIMS: To study the expression of the MUC1 extracellular
      subunit in cell nuclei of neoplastic breast, head and neck, and colon samples.
      MATERIALS AND METHODS: 330 primary tumor samples were analyzed: 166 invasive
      breast carcinomas, 127 head and neck tumors, and 47 colon tumors; 10 benign
      breast disease (BBD) and 40 normal specimens were also included. A standard
      immunohistochemical method with antigen retrieval was performed. Nuclear
      fractions from tissue homogenates and breast cancer cell lines (ZR-75, MDA-MB
      231, MCF7, and T47D) were obtained and analyzed by Western blotting (WB). The
      anti-MUC1 extracellular subunit monoclonal antibody HMFG1 was used for
      immunohistochemistry. RESULTS: 37/166 breast cancer specimens, 5/127 head and
      neck cancer specimens, 2/47 colon cancer samples, and 3/10 BBD samples showed
      immunohistochemical staining at the nuclear level. No nuclear reaction was
      detected in normal samples. By WB, breast and colon cancer purified nuclear
      fractions showed reactivity at 200 kDa in 3/30 breast and 3/20 colon cancer
      samples as well as purified nuclear fractions obtained from breast cancer cell
      lines. CONCLUSIONS: This study shows that the MUC1 extracellular domain might be
      translocated to the cell nucleus in breast, head and neck, and colon cancer as
      well as BBD.

PMID- 25982682
TI  - Germ cell tumors overexpress the candidate therapeutic target cyclin B1
      independently of p53 function.
AB  - Germ cell tumors (GCTs) generally express wild-type p53 protein. Rare p53
      mutations may be associated with cisplatin resistance. There is growing interest
      in the role of cyclins as targets for GCTs. Cyclin B1 is involved in G2/M
      transition and its overexpression has been reported in tumors carrying
      nonfunctional p53. Conversely, cyclin B1-specific small interfering RNAs have
      been shown to dramatically reduce tumor proliferation. We investigated whether a
      subset of chemotherapy-resistant GCTs overexpressed cyclin B1 as a result of
      nonfunctional p53, as this would make cyclin B1 a potential therapeutic target.
      Our data showed that GCTs consistently overexpressed cyclin B1 independently of
      their responsiveness to chemotherapy or the presence of p53 mutations. Cyclin B1
      was overexpressed by GCT cell lines carrying functional p53. Cyclin B1-specific
      small interfering RNAs only slightly reduced the proliferation of JAR and JEG-3
      placental choriocarcinoma cells. Further research into targeting cyclin B1 could
      provide a novel intervention for GCTs. 

PMID- 25982683
TI  - Identifying novel biomarkers of gastric cancer through integration analysis of
      single nucleotide polymorphisms and gene expression profile.
AB  - PURPOSE: Single nucleotide polymorphisms (SNPs) are an important cause of
      functional variation in proteins leading to tumorigenesis. We aimed to identify
      candidate biomarkers with polymorphisms in gastric cancer (GC). METHODS: The SNP
      microarray profile GSE29996 including 50 GC samples and 50 normal controls, and
      gene expression data GSE56807 consisting of 5 GC samples and 5 controls were
      downloaded from the Gene Expression Omnibus database. After preprocessing of raw
      data, GC-associated SNPs were identified using the Cochran-Armitage trend test,
      and differentially expressed genes (DEGs) were screened out using the limma
      package in R. Significant DEGs with risk associated SNP loci were screened using
      the Fisher combination test. Gene ontology function and pathway enrichment
      analyses were performed for DEGs with risk associated SNP loci by GenCLip online
      tool. Transcriptional regulatory analysis was also conducted for transcription
      factor and target DEGs. RESULTS: A total of 79 DEGs with risk associated SNP loci
      were identified from GC samples compared with normal controls. These DEGs were
      mainly enriched in anatomical structure development, including embryo
      development. Additionally, DEGs were significantly involved in the NO1 pathway,
      including actin, alpha 1, skeletal muscle (ACTA1). In the regulatory network,
      transcription factor forkhead box L1 (FOXL1) regulated 26 DEGs with risk
      associated SNP loci, including Iroquois homeobox 1 (IRX1) rs11134044, sex
      determining region Y (SRY)-box1 (SOX1) rs9549447 and msh homeobox 1 (MSX1)
      rs41451149. CONCLUSIONS: IRX1, SOX1 and MSX1 with risk associated SNP loci may
      serve as candidate biomarkers for diagnosis and prognosis of GC.

PMID- 25982684
TI  - Alpha-methylacyl-CoA racemase and hepsin as urinary prostate cancer markers.
AB  - BACKGROUND: Because of the numerous limitations of prostate-specific antigen
      (PSA), alpha-methylacyl-CoA racemase (AMACR) and hepsin have recently been
      suggested as potential biomarkers in prostate cancer (PC). This report presents a
      comparison study of the presence of AMACR and hepsin in urine collected before
      and after digital rectal examination (DRE) as a previously suggested diagnostic
      marker for PC. METHODS: Seventy-six urine samples (38 before and 38 after
      prostate massage) from patients with benign prostate hyperplasia (BPH) and 66
      urine samples (33 before and 33 after prostate massage) from patients with PC
      were analyzed. PC was confirmed by prostate biopsy. Urinary levels of AMACR and
      hepsin were determined by ELISA and related to the tumor stage, Gleason score and
      PSA level. RESULTS: AMACR and hepsin levels in urine collected after prostate
      massage were higher only in the PC group. There were no correlations between
      AMACR levels, hepsin levels, tumor stage and Gleason score. AMACR and hepsin did
      not differentiate between BPH and PC with better true positive and false negative
      rates than serum PSA. CONCLUSIONS: AMACR and hepsin were unable to diagnose PC
      with better true positive and false negative rates than PSA. An additional
      procedure combined with other markers should be applied for the reliable
      diagnosis of PC.

PMID- 25982685
TI  - When in Rome, do as the Romans do?

PMID- 25982686
TI  - Aqueductal Stenosis Has a New Dimension--Aspergillosis: A Rare Case Report and
      Review of the Literature.
AB  - BACKGROUND: Cerebral aspergillosis, often encountered in immunocompromised
      patients, is almost always fatal despite radical surgical and medical management
      and frequently is a finding at autopsy. Attempts at fungal isolation often are
      unsuccessful, and a high index of radiologic suspicion is necessary. CASE
      DESCRIPTION: A premature, 5-month-old female infant, born via normal vaginal
      delivery, presented with a progressive increase in head size since birth, delayed
      developmental milestones, and intermittent vomiting for 1 month. There was no
      history of trauma and no evidence of diabetes mellitus or hypertension, family
      history of tuberculosis, gestational diabetes, jaundice, or febrile eruptions.
      Neonatal jaundice was present after day 1, remained for 2 days, and was treated
      with phototherapy. Findings of the general and systemic examinations were
      unremarkable. Findings of a neurologic examination revealed a hypoactive infant
      with papilledema and extensor plantar bilaterally. Computed tomography scan of
      brain showed hydrocephalus attributable to aqueductal stenosis. On endoscopic
      third ventriculostomy, dense, friable, whitish yellow, nonvascular masses were
      encountered in the third ventricle, obstructing it. Her endoscopic third
      ventriculostomy success score was 10 + 0 + 10 = 20%. Histopathologic examination
      and culture revealed Aspergillus flavus. A week later, a medium-pressure
      ventriculoperitoneal shunt was done, and voriconazole was added. RESULTS: At
      discharge on the 7th postoperative day, 4 weeks and 12 weeks later (ie, first and
      second follow-up) the child was active, playful, and feeding normally. The first
      reported case of an aqueductal stenosis due to aspergillosis was in 2000 by van
      Landeghem FK et al. (Clin Neuropathol 19:26-29, 2000). To the best of our
      knowledge, this may only be the second reported case of hydrocephalus
      attributable to aqueductal stenosis caused by Aspergillosis. In conclusion,
      aspergillosis should not be ruled out as a differential diagnosis in aqueductal
      stenosis, even when the patient seems to be immunocompetent.

PMID- 25982687
TI  - Clinical Outcomes of Daptomycin for Vancomycin-resistant Enterococcus Bacteremia.
AB  - PURPOSE: In light of recent evidence suggesting enhancement of daptomycin
      activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other
      beta-lactam antibiotics, we evaluated the safety profile and clinical efficacy of
      daptomycin with and without concomitant beta-lactam antimicrobials in the
      treatment of VRE (faecium or faecalis) bacteremia from multiple centers across
      the United States. METHODS: Data were collected retrospectively as part of a
      larger multicenter registry (The Cubicin Outcomes Registry and Experience).
      Efficacy and clinical outcomes in patients with VRE bacteremia who received at
      least 3 days of daptomycin with or without concomitant beta-lactams were
      analyzed. Although all the cases involved daptomycin-susceptible VRE, additional
      analysis was performed to examine whether the adjunctive beta-lactam would play a
      more pivotal role in cases where the daptomycin MIC was in the upper limit of the
      susceptibility range, indicating that daptomycin monotherapy efficacy may be
      relatively compromised compared with cases with lower daptomycin MICs. FINDINGS:
      Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients
      had at least one significant comorbidity, such as solid-organ or bone marrow
      transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical
      illness (36%) requiring care in an intensive care unit. Overall treatment success
      was 86% (n = 225/262), and treatment success for patients taking concomitant beta
      lactams was 86% (n = 105/122). Logistic regression identified treatment failure
      to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated
      daptomycin MIC (3-4 ug/mL) (odds ratio = 3.23, P = 0.013). No significant
      increase in clinical failure was seen among patients with elevated daptomycin MIC
      who received concomitant beta-lactam therapy (clinical success, 88% vs 79% for
      MIC <=2 vs 3-4 ug/mL, respectively; P = 0.417). Of 262 patients, 33 (13%)
      experienced >=1 adverse event possibly related to daptomycin (increased creatine
      kinase in 8 patients). IMPLICATIONS: Overall, daptomycin was effective and well
      tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC
      of 3 to 4 ug/mL. Concomitant beta-lactam therapy with daptomycin may improve
      clinical outcomes in this setting. Further studies are needed to characterize the
      potential benefit of concomitant beta-lactams with daptomycin.

PMID- 25982689
TI  - Within-island speciation with an exceptional case of distinct separation between
      two sibling lizard species divided by a narrow stream.
AB  - Delimitation of genetic and geographic boundaries between species is a focus of
      evolutionary biology. In this study, we demonstrated fine-scale differentiation
      of Takydromus formosanus species complex comprising four insular endemics on
      Taiwan Island. Phylogeny and ancestral range reconstruction based on
      mitochondrial DNA sequences of 430 Takydromus lizards (405 lizards of this
      complex throughout their distribution range, and 25 lizards from 11 other
      species) indicated that the major branching process occurred within Taiwan, which
      represented a solid evidence of within-island speciation on this small island. We
      further demonstrated an exceptional case of a pair of sister species, T.
      viridipunctatus and T. luyeanus, that were separated by a narrow stream with a
      width of only 15m. This pattern might be one of the narrowest contact zones ever
      documented in terrestrial vertebrates. To evaluate the level of genetic
      introgression between these sister species, a fine-scale collection of another
      382 lizards was conducted along a transect line across the stream. A total of 13
      microsatellite markers and mtDNA genotyping was used to detect a low proportion
      of hybrids (5.7-9.9% from STRUCTURE, and 2.3% from DAPC). Our results indicated
      that the two clades are highly differentiated across this extremely short
      distance. 

PMID- 25982688
TI  - Activation of tumour cell ECM degradation by thrombin-activated platelet
      membranes: potentially a P-selectin and GPIIb/IIIa-dependent process.
AB  - The promotion of tumour metastasis by platelets may occur through several
      mechanisms including the induction of a more metastatic phenotype in tumour cells
      and assisted extravasation of circulating tumour cells. Whilst the mechanisms
      underlying platelet-assisted extravasation have been extensively studied, much
      less attention has been paid to the mechanisms underlying platelet promotion of
      an aggressive phenotype within a tumour cell population. Herein, we demonstrate
      in vitro that MDA-MB-231 breast carcinoma cells incubated with washed thrombin
      activated platelet membranes adopt a Matrigel-degrading phenotype in a dose- and
      contact time-dependent manner. The same phenotypic change was observed with three
      other human tumour cell lines of diverse anatomical origin. Moreover, tumour cell
      lines that had been cultured with washed thrombin-activated platelet membranes
      had a greater metastatic capacity when injected into mice. This in vivo effect
      was reliant upon a co-incubation period of >2 h implying a mechanism involving
      more than platelet membrane binding that occurred within 5 min. Upon further
      investigation it was found that simultaneous blocking of the platelet-membrane
      proteins P-selectin and GPIIb/IIIa prevented interactions between platelet
      membranes and MDA-MB-231 cells but also significantly reduced the ability of
      tumour cells to degrade Matrigel. These results confirm that platelets induce a
      more aggressive phenotype in tumour cells but also identify the platelet proteins
      involved in this effect. P-selectin and GPIIb/IIIa also play a role in assisting
      tumour cell extravasation and, thus, are ideal targets for the therapeutic
      intervention of both stages of platelet-assisted metastasis.

PMID- 25982690
TI  - A multilocus analysis provides evidence for more than one species within Eugenes
      fulgens (Aves: Trochilidae).
AB  - The status of subspecies in systematic zoology is the focus of controversy.
      Recent studies use DNA sequences to evaluate the status of subspecies within
      species complexes and to recognize and delimit species. Here, we assessed the
      phylogenetic relationships, the taxonomic status of the proposed subspecies, and
      the species limits of the monotypic hummingbird genus Eugenes (E. fulgens with
      traditionally recognized subspecies E. f. fulgens, E. f. viridiceps, and E. f.
      spectabilis), using nuclear (Beta Fibrinogen BFib, Ornithine Decarboxylase ODC,
      and Muscle Skeletal Receptor Tyrosine Kinase MUSK) and mitochondrial (NADH
      dehydrogenase subunit 2 ND2, NADH dehydrogenase subunit 4 ND4, and Control Region
      CR) markers. We performed Bayesian and Bayesian Phylogenetics and Phylogeography
      analyses and found genetic differences between the three groups, suggesting the
      existence of two cryptic species (E. fulgens and E. viridiceps) and one
      phenotypically differentiated species (E. spectabilis). Our analyses show that
      the E. viridiceps and E. fulgens groups are more closely related with one another
      than with E. spectabilis. 

PMID- 25982691
TI  - Plasma membrane targeting by short chain sphingolipids inserted in liposomes
      improves anti-tumor activity of mitoxantrone in an orthotopic breast carcinoma
      xenograft model.
AB  - Mitoxantrone (MTO) is clinically used for treatment of various types of cancers
      providing an alternative for similarly active, but more toxic chemotherapeutic
      drugs such as anthracyclines. To further decrease its toxicity MTO was
      encapsulated into liposomes. Although liposomal drugs can accumulate in target
      tumor tissue, they still face the plasma membrane barrier for effective
      intracellular delivery. Aiming to improve MTO tumor cell availability, we used
      short chain lipids to target and modulate the tumor cell membrane, promoting MTO
      plasma membrane traversal. MTO was encapsulated in liposomes containing the short
      chain sphingolipid (SCS), C8-Glucosylceramide (C8-GluCer) or C8
      Galactosylceramide (C8-GalCer) in their bilayer. These new SCS-liposomes
      containing MTO (SCS-MTOL) were tested in vivo for tolerability, pharmacokinetics,
      biodistribution, tumor drug delivery by intravital microscopy and efficacy, and
      compared to standard MTO liposomes (MTOL) and free MTO. Liposomal encapsulation
      decreased MTO toxicity and allowed administration of higher drug doses. SCS-MTOL
      displayed increased clearance and lower skin accumulation compared to standard
      MTOL. Intratumoral liposomal drug delivery was heterogeneous and rather limited
      in hypoxic tumor areas, yet SCS-MTOL improved intracellular drug uptake in
      comparison with MTOL. The increased MTO availability correlated well with the
      improved antitumor activity of SCS-MTOL in a MDAMB-231 breast carcinoma model.
      Multiple dosing of liposomal MTO strongly delayed tumor growth compared to free
      MTO and prolonged mouse survival, whereas among the liposomal MTO treatments, C8
      GluCer-MTOL was most effective. Targeting plasma membranes with SCS improved MTO
      tumor availability and thereby therapeutic activity and represents a promising
      approach to improve MTO-based chemotherapy. 

PMID- 25982692
TI  - Plasma N-terminal pro-B-type natriuretic peptide concentration in healthy retired
      racing Greyhounds.
AB  - BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac
      biomarker whose plasma concentration is high in some dogs with cardiopulmonary
      disease. NT-proBNP is a diagnostic tool that can be used to help determine if a
      patient has congestive heart failure. Greyhounds have functional heart murmurs,
      relative cardiomegaly, and high serum cTnI concentration. OBJECTIVES: The purpose
      of the study was to evaluate the plasma concentration of NT-proBNP in healthy
      Greyhounds and compare it to non-Greyhound dogs. METHODS: We prospectively
      evaluated healthy client-owned dogs including retired racing Greyhounds and non
      Greyhounds. Plasma was obtained and transferred into tubes containing a protease
      inhibitor and submitted for a specific NT-proBNP ELISA assay. RESULTS: The plasma
      NT-proBNP concentration in Greyhounds was significantly higher than in non
      Greyhound control dogs (946 vs 632 pmol/L; P < .005); 46% of Greyhounds had NT
      proBNP > 1000 pmol/L. CONCLUSIONS: Plasma NT-proBNP concentration in Greyhounds
      is high and should be interpreted with caution.

PMID- 25982693
TI  - High rate of sickle cell anaemia in Sub-Saharan Africa underlines the need to
      screen all children with severe anaemia for the disease.
AB  - AIM: Neonatal screening for sickle cell anaemia is not common practice in the
      Democratic Republic of Congo, and we determined the prevalence in children with
      unknown electrophoresis of haemoglobin and anaemia. METHODS: A cross-sectional
      study was conducted in four hospitals in the country's capital Kinshasa. RESULTS:
      We screened 807 patients with anaemia (Hb < 6 g/dL) for sickle cell disease. The
      overall mean age at presentation was 42.7 months +/- 29.7 months, and most
      patients (76.3%) were less than five years of age, with a peak incidence at seven
      to 36 months of age (45%). The median age at the first transfusion was 29 months
      (range 4-159 months). Of these 807 children, 36 (4.5%) were homozygous for
      haemoglobin S disease and 45 (5.6%) were heterozygotes. The proportion of
      patients with homozygous sickle cell anaemia was slightly higher in children with
      a medical history of hand foot syndrome, in children who had received more than
      three transfusions and in children up to 36 months of age at their first
      transfusion. CONCLUSION: The high prevalence of sickle cell anaemia in children
      in Sub-Saharan Africa underlines the need for neonatal screening or, if that is
      not possible, screening of all children with severe anaemia to identify patients
      with the disease and provide early management.

PMID- 25982694
TI  - Evolution of the hippocampus in reptiles and birds.
AB  - Although the hippocampus is structurally quite different among reptiles, birds,
      and mammals, its function in spatial memory is said to be highly conserved. This
      is surprising, given that structural differences generally reflect functional
      differences. Here I review this enigma in some detail, identifying several
      evolutionary changes in hippocampal cytoarchitecture and connectivity. I
      recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes,
      and the tuatara Sphenodon) that differs substantially from the pattern of
      organization observed in the turtle/archosaur lineage, which includes
      crocodilians and birds. Although individual subdivisions of the hippocampus are
      difficult to homologize between these two patterns, both lack a clear homolog of
      the mammalian dentate gyrus. The strictly trilaminar organization of the
      ancestral amniote hippocampus was gradually lost in the lineage leading to birds,
      and birds expanded the system of intrahippocampal axon collaterals, relative to
      turtles and lizards. These expanded collateral axon branches resemble the
      extensive collaterals in CA3 of the mammalian hippocampus but probably evolved
      independently of them. Additional examples of convergent evolution between birds
      and mammals are the loss of direct inputs to the hippocampus from the primary
      olfactory cortex and the general expansion of telencephalic regions that
      communicate reciprocally with the hippocampus. Given this structural convergence,
      it seems likely that some similarities in the function of the hippocampus between
      birds and mammals, notably its role in the ability to remember many different
      locations without extensive training, likewise evolved convergently. The
      currently available data do not allow for a strong test of this hypothesis, but
      the hypothesis itself suggests some promising new research directions.

PMID- 25982695
TI  - Mixed infections reveal virulence differences between host-specific bee
      pathogens.
AB  - Dynamics of host-pathogen interactions are complex, often influencing the
      ecology, evolution and behavior of both the host and pathogen. In the natural
      world, infections with multiple pathogens are common, yet due to their
      complexity, interactions can be difficult to predict and study. Mathematical
      models help facilitate our understanding of these evolutionary processes, but
      empirical data are needed to test model assumptions and predictions. We used two
      common theoretical models regarding mixed infections (superinfection and co
      infection) to determine which model assumptions best described a group of fungal
      pathogens closely associated with bees. We tested three fungal species,
      Ascosphaera apis, Ascosphaera aggregata and Ascosphaera larvis, in two bee hosts
      (Apis mellifera and Megachile rotundata). Bee survival was not significantly
      different in mixed infections vs. solo infections with the most virulent pathogen
      for either host, but fungal growth within the host was significantly altered by
      mixed infections. In the host A. mellifera, only the most virulent pathogen was
      present in the host post-infection (indicating superinfective properties). In M.
      rotundata, the most virulent pathogen co-existed with the lesser-virulent one
      (indicating co-infective properties). We demonstrated that the competitive
      outcomes of mixed infections were host-specific, indicating strong host
      specificity among these fungal bee pathogens. 

PMID- 25982697
TI  - Vaccine-induced Abeta-specific CD8+ T cells do not trigger autoimmune
      neuroinflammation in a murine model of Alzheimer's disease.
AB  - BACKGROUND: Active immunization against Abeta was reported to have a therapeutic
      effect in murine models of Alzheimer's disease. Clinical Abeta vaccination trial
      AN1792 was interrupted due to the development in 6 % of the patients of
      meningoencephalitis likely involving pro-inflammatory CD4(+) T cells. However,
      the potential implication of auto-aggressive anti-Abeta CD8(+) T cells has been
      poorly investigated. METHODS: Potential MHC-I-restricted Abeta-derived epitopes
      were first analyzed for their capacity to recruit functional CD8(+) T cell
      responses in mouse models. Their impact on migration of CD8(+) T cells into the
      brain parenchyma and potential induction of meningoencephalitis and/or neuronal
      damage was investigated upon vaccination in the APPPS1 mouse model of AD.
      RESULTS: We identified one nonamer peptide, Abeta33-41, which was naturally
      processed and presented in association with H-2-D(b) molecule on neurons and
      CD11b(+) microglia. Upon optimization of anchor residues for enhanced binding to
      H-2-D(b), immunization with the modified Abeta33-41NP peptide elicited Abeta
      specific IFNgamma-secreting CD8(+) T cells, which are cytotoxic towards Abeta
      expressing targets. Whereas T cell infiltration in the brain of APPPS1 mice is
      dominated by CD3(+)CD8(-) T cells and increases with disease evolution between 4
      and 7 months of age, a predominance of CD3(+)CD8(+) over CD3(+)CD8(-) cells was
      observed in 6- to 7-month-old APPPS1 but not in WT animals, only after
      vaccination with Abeta33-41NP. The number of CD11b(+) mononuclear phagocytes,
      which significantly increases with age in the brain of APPPS1 mice, was reduced
      following immunization with Abeta33-41NP. Despite peripheral activation of Abeta
      specific CD8(+) cytotoxic effectors and enhanced infiltration of CD8(+) T cells
      in the brain of Abeta33-41NP-immunized APPPS1 mice, no clinical signs of severe
      autoimmune neuroinflammation were observed. CONCLUSIONS: Altogether, these
      results suggest that Abeta-specific CD8(+) T cells are not major contributors to
      meningoencephalitis in response to Abeta vaccination.

PMID- 25982698
TI  - Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.
AB  - BACKGROUND: Obesity can cause pathological changes in organs. We determined the
      effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm
      providing organ protection, on mouse heart. METHODS: Seven-week old CD1 male mice
      were randomly assigned to control, HFD and intermittent fasting groups. Control
      mice had free access to regular diet (RD). RD was provided every other day to
      mice in the intermittent fasting group. Mice in HFD group had free access to HFD.
      Their left ventricles were harvested 11 months after they had been on these diet
      regimens. RESULTS: HFD increased cardiomyocyte cross-section area and fibrosis.
      HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule
      associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD
      increased the phospho-glycogen synthase kinase-3beta (GSK-3beta) at Ser9, a sign
      of GSK-3beta inhibition. Nuclear GATA binding protein 4 and yes-associated
      protein, two GSK-3beta targeting transcription factors that can induce
      hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on
      intermittent fasting did not have these changes except for the increased active
      caspase 3 and decreased ratio of LC3II/LC3I. CONCLUSIONS: These results suggest
      that chronic HFD induces myocardial hypertrophy and fibrosis, which may be
      mediated by GSK-3beta inhibition.

PMID- 25982699
TI  - Magnetic resonance imaging reveals altered distribution of hepatic fat in
      children with type 1 diabetes compared to controls.
AB  - INTRODUCTION: Children with type 1 diabetes have been identified as a risk group
      for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total
      hepatic fat fraction and fat distribution across Couinaud segments in children
      with type 1 diabetes and controls and the relation of hepatic fat to plasma and
      anthropometric parameters. METHODS: Hepatic fat fraction and fat distribution
      across Couinaud segments were measured with magnetic resonance imaging (MRI) in
      22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric
      data were collected. RESULTS: No children had NAFLD. Children with type 1
      diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls
      (median 1.8%), and their fat had a different segmental distribution. The fat
      fraction of segment V was the most representative of the liver as a whole. An
      incidental finding was that diabetes patients treated with multiple daily
      injections of insulin (MDI) had a fat distribution more similar to controls than
      patients with continuous subcutaneous insulin infusion (CSII). CONCLUSIONS: In
      children with type 1 diabetes, NAFLD may be less common than recent studies have
      suggested. Children with type 1 diabetes may have a lower fat fraction and a
      different fat distribution in the liver than controls. Diabetes treatment with
      MDI or CSII may affect liver fat, but this needs to be confirmed in a larger
      sample of patients. The heterogeneity of hepatic fat infiltration may affect
      results when liver biopsy is used for diagnosing fatty liver.

PMID- 25982701
TI  - Selection of solid-state forms: challenges, opportunities, lessons learned and
      adventures from recent years.

PMID- 25982700
TI  - The prevalence and risk of metabolic syndrome and its components among people
      with posttraumatic stress disorder: a systematic review and meta-analysis.
AB  - OBJECTIVE: People with posttraumatic stress disorder (PTSD) have a higher
      mortality than the general population, mainly due to cardiovascular diseases
      (CVD). Metabolic syndrome (MetS) and its components are highly predictive of CVD.
      The aim of this meta-analysis was to describe pooled frequencies of MetS and its
      components in people with PTSD and to compare MetS prevalence in PTSD versus the
      general population. METHOD: Medline, PsycARTICLES, Embase and CINAHL were
      searched until 02/2015 for cross-sectional and baseline data of longitudinal
      studies in adults with PTSD. Two independent reviewers conducted the searches and
      extracted data. Random effects meta-analysis with a relative risk, subgroups and
      meta-regression analyses were employed. RESULTS: Overall, 9 studies met the
      inclusion criteria including 9,673 individuals in midlife with PTSD and 6852
      general population controls. The pooled MetS prevalence was 38.7% (95% CI = 32.1%
      45.6%; Q = 52.1, p < 0.001; N = 9; n = 9,673; age range = 44-61 years). Abdominal
      obesity was observed in 49.3% (95% CI = 29.7%-69.0%), hyperglycemia in 36.1% (95%
      CI = 18.8%-55.6%), hypertriglyceridemia in 45.9% (95% CI = 12.2%-81.9%), low high
      density-lipoprotein-cholesterol in 46.4% (95% CI = 26.4%-67.0%) and hypertension
      in 76.9% (95% CI = 67.9%-84.8%). The MetS prevalence was consistently high across
      geographical regions, settings or populations (war veterans or not). Compared
      with matched general population controls, people with PTSD had an almost double
      increased risk for MetS (RR = 1.82; 95% CI = 1.72-1.92; p < 0.001). Most analyses
      were not statistically heterogeneous. CONCLUSIONS: MetS is highly prevalent in
      people with PTSD. Routine screening and multidisciplinary management of medical
      and behavioral conditions is needed. Future research should focus on how cardio
      metabolic outcomes are moderated by clinical and treatment characteristics and
      genetic factors.

PMID- 25982702
TI  - Exosomes: Potent regulators of tumor malignancy and potential bio-tools in
      clinical application.
AB  - Multiple lines of evidence indicate that exosomes, as efficient messengers in
      cell-to-cell communication, play pleiotropic roles in regulating tumor
      malignancy. The cargos (proteins, mRNAs, and miRNAs) carried by exosomes can be
      functionally delivered between different types of cells and even transferred to
      distant locations, influencing the biological activities of tumor and non-tumor
      cells and promoting tumor growth, invasion, metastasis, angiogenesis, and drug
      resistance. Tumor-associated exosomes have been identified in biological (plasma,
      urine, saliva) and pathological (malignant effusions, pleural effusions, ascites)
      fluids from cancer patients. The contents of exosomes may vary depending on tumor
      types and status. Detection of exosomes in biofluids of cancer patients may
      represent a promising strategy to gain pathogenic information and to select
      specific biomarkers for the diagnosis and prognosis of cancer. Utilization of
      exosomes as delivery vehicles for siRNAs and therapeutic drugs brings out new
      concepts such as biomimetics in cancer treatment. In this review, we will mainly
      discuss emerging roles of exosomes in tumor invasion, metastasis, angiogenesis,
      and drug resistance and potential clinical application of exosomes as biomarkers
      and therapeutic tools. 

PMID- 25982703
TI  - Distance from practice moderates the relationship between patient management
      involving nurse telephone triage consulting and patient satisfaction with care.
AB  - The ESTEEM trial was a randomised-controlled trial of telephone triage
      consultations in general practice. We conducted exploratory analyses on data from
      9154 patients from 42 UK general practices who returned a questionnaire
      containing self-reported ratings of satisfaction with care following a request
      for a same-day consultation. Mode of care was identified through case notes
      review. There were seven main types: a GP face-to-face consultation, GP or nurse
      telephone triage consultation with no subsequent same day care, or a GP or nurse
      telephone triage consultation with a subsequent face-to-face consultation with a
      GP or a nurse. We investigated the contribution of mode of care to patient
      satisfaction and distance between the patient's home and the practice as a
      potential moderating factor. There was no overall association between patient
      satisfaction and distance from practice. However, patients managed by a nurse
      telephone consultation showed lowest levels of satisfaction, and satisfaction for
      this group of patients increased the further they lived from the practice. There
      was no association between any of the other modes of management and distance from
      practice. 

PMID- 25982704
TI  - Therapeutic landscapes and wellbeing in later life: Impacts of blue and green
      spaces for older adults.
AB  - This paper extends the concept of therapeutic landscapes by investigating how
      green and blue spaces affect older adult health and wellbeing. We draw on
      interview data from participants aged 65-86 years old who described their
      everyday experiences with green and especially blue spaces across Metro
      Vancouver, Canada. Landscapes embedded with therapeutic qualities included parks,
      gardens, street greenery, lakes, and the ocean. Interactions with these spaces
      influenced participants' perceived physical, mental, and social health. Issues of
      safety, accessibility, and personal perception complicated this relationship.
      Overall, the findings indicate that nature plays a nuanced and influential role
      in the everyday lives of older adults. Better understanding how older adults
      experience health and landscape is critical towards developing everyday contact
      with nature that can improve quality of life for ageing populations. 

PMID- 25982705
TI  - Psychosexual therapy and education in patients treated for cancer of the head and
      neck.
AB  - It is now widely accepted that cancer is a chronic disease, and in this context
      we have previously highlighted shortcomings in the assessment of problems with
      intimacy and sexuality in patients treated for cancer of the head and neck. In
      this paper we introduce established strategies for the diagnosis and treatment of
      psychosexual problems to support these patients, and describe our early
      experiences of their use. We include brief narratives and case reports to show
      how they have made a difference to patients and their partners. 

PMID- 25982706
TI  - Performance of the WeNMR CS-Rosetta3 web server in CASD-NMR.
AB  - We present here the performance of the WeNMR CS-Rosetta3 web server in CASD-NMR,
      the critical assessment of automated structure determination by NMR. The CS
      Rosetta server uses only chemical shifts for structure prediction, in
      combination, when available, with a post-scoring procedure based on unassigned
      NOE lists (Huang et al. in J Am Chem Soc 127:1665-1674, 2005b, doi:
      10.1021/ja047109h). We compare the original submissions using a previous version
      of the server based on Rosetta version 2.6 with recalculated targets using the
      new R3FP fragment picker for fragment selection and implementing a new annotation
      of prediction reliability (van der Schot et al. in J Biomol NMR 57:27-35, 2013,
      doi: 10.1007/s10858-013-9762-6), both implemented in the CS-Rosetta3 WeNMR
      server. In this second round of CASD-NMR, the WeNMR CS-Rosetta server has
      demonstrated a much better performance than in the first round since only
      converged targets were submitted. Further, recalculation of all CASD-NMR targets
      using the new version of the server demonstrates that our new annotation of
      prediction quality is giving reliable results. Predictions annotated as weak are
      often found to provide useful models, but only for a fraction of the sequence,
      and should therefore only be used with caution.

PMID- 25982708
TI  - Rh(V) -Nitrenoid as a Key Intermediate in Rh(III) -Catalyzed Heterocyclization by
      C-H Activation: A Computational Perspective on the Cycloaddition of Benzamide and
      Diazo Compounds.
AB  - A mechanistic study of the substituent-dependent ring formations in Rh(III) 
      catalyzed C-H activation/cycloaddition of benzamide and diazo compounds was
      carried out by using DFT calculations. The results indicated that the
      decomposition of the diazo is facilitated upon the formation of the five-membered
      rhodacycle, in which the Rh(III) center is more electrophilic. The insertion of
      carbenoid into Rh-C(phenyl) bond occurs readily and forms a 6-membered
      rhodacycle, however, the following C-N bond formation is difficult both
      kinetically and thermodynamically by reductive elimination from the Rh(III)
      species. Instead, the Rh(V) -nitrenoid intermediate could be formed by migration
      of the pivalate from N to Rh, which undergoes the heterocyclization much more
      easily and complementary ring-formations could be modulated by the nature of the
      substituent at the alpha-carbon. When a vinyl is attached, the stepwise 1,3
      allylic migration occurs prior to the pivalate migration and the 8-membered ring
      product will be formed. On the other hand, the pivalate migration becomes more
      favorable for the phenyl-contained intermediate because of the difficult 1,3
      allylic migration accompanied by dearomatization, thus the 5-membered ring
      product was formed selectively.

PMID- 25982707
TI  - Potassium urinary excretion and dietary intake: a cross-sectional analysis in 8
      10 year-old children.
AB  - BACKGROUND: Data from studies assessing the intake of potassium, and the
      concomitant sodium-to-potassium ratio are limited. The aim of this study was to
      evaluate potassium and sodium-to-potassium ratio intake in 8-10 year-old
      children. METHODS: A cross-sectional survey was carried out from January to June
      2014 and data from 163 children (81 boys) were included. Potassium intake was
      estimated by 24-h urine collection and coefficient of creatinine was used to
      validate completeness of urine collections. Urinary sodium and sodium-to
      potassium ratio were also analysed. A 24-h dietary recall was used to provide
      information on dietary sources of potassium. Height and weight were measured
      according to international standards. RESULTS: The mean urinary potassium
      excretion was 1701 +/- 594 mg/day in boys, and 1682 +/- 541 mg/day in girls (p =
      0.835); 8.0% of children met the WHO recommendations for potassium intake. The
      mean sodium excretion was 2935 +/- 1075 mg/day in boys and 2381 +/- 1045 mg/day
      in girls (p <0.001) and urinary sodium-to-potassium ratio was 3.2 +/- 1.4 in
      boys, and 2.5 +/- 1.1 in girls (p = 0.002). The mean fruit and vegetable intake
      was 353.1 +/- 232.5 g/day in boys, and 290.8 +/- 213.1 g/day in girls (p =
      0.101). CONCLUSIONS: This study reported a low compliance of potassium intake
      recommendations in 8-10 year-old children. Health promotion interventions are
      needed in order to broaden public awareness of potassium inadequacy and to
      increase potassium intake.

PMID- 25982709
TI  - Global survey of the diagnostic evaluation and management of cryptogenic ischemic
      stroke.
AB  - BACKGROUND: About 25% of ischemic strokes are categorized as cryptogenic (i.e. of
      unknown cause), but few data exist about the extent of diagnostic testing or
      treatment. We undertook an international survey to characterize current
      diagnostic evaluation and antithrombotic management of patients with cryptogenic
      ischemic stroke in 2014. AIMS/HYPOTHESIS: To determine the type of diagnostic
      evaluation undertaken for cryptogenic ischemic stroke and antithrombotic
      management and to compare across global regions. METHODS: An 18-question online
      survey was sent to 995 physicians involved in stroke care in 61 countries.
      Countries were separated into World Bank global regions and income groups.
      Diagnostic tests were considered routine if performed in >75% of patients at a
      center. RESULTS: Three hundred one completed surveys were received from 48
      countries (response rate ~30%). The majority (82%) of hospitals were from high
      income countries and mainly from Europe and Central Asia (56%) and North America
      (19%). For ischemic stroke patients, magnetic resonance imaging is routinely
      obtained at 36% of hospitals (highest in North America, 58%). Among cryptogenic
      stroke patients, transesophageal echocardiography is routinely performed in 17%
      of hospitals. More than 24 hour cardiac rhythm monitoring is done routinely at
      relatively few (17%) hospitals (highest in North America, 33%). Intracranial
      arterial imaging is done routinely at 70% of hospitals, with no significant
      regional differences. Antiplatelet therapies are routinely prescribed for
      secondary prevention at 94% of hospitals. CONCLUSIONS: Based on self-selected
      respondents from a large number of international stroke centers, transesophageal
      echocardiography and prolonged (>24 h) cardiac rhythm monitoring are not
      routinely performed in cryptogenic stroke patients, even in high-income
      countries. Antiplatelet therapy is the global standard for secondary prevention
      of cryptogenic stroke.

PMID- 25982710
TI  - [Neurodegenerative diseases 2014-2019: A plan without perineum].

PMID- 25982711
TI  - How does image noise affect actual and predicted human gaze allocation in
      assessing image quality?
AB  - A central research question in natural vision is how to allocate fixation to
      extract informative cues for scene perception. With high quality images,
      psychological and computational studies have made significant progress to
      understand and predict human gaze allocation in scene exploration. However, it is
      unclear whether these findings can be generalised to degraded naturalistic visual
      inputs. In this eye-tracking and computational study, we methodically distorted
      both man-made and natural scenes with Gaussian low-pass filter, circular
      averaging filter and Additive Gaussian white noise, and monitored participants'
      gaze behaviour in assessing perceived image qualities. Compared with original
      high quality images, distorted images attracted fewer numbers of fixations but
      longer fixation durations, shorter saccade distance and stronger central fixation
      bias. This impact of image noise manipulation on gaze distribution was mainly
      determined by noise intensity rather than noise type, and was more pronounced for
      natural scenes than for man-made scenes. We furthered compared four high
      performing visual attention models in predicting human gaze allocation in
      degraded scenes, and found that model performance lacked human-like sensitivity
      to noise type and intensity, and was considerably worse than human performance
      measured as inter-observer variance. Furthermore, the central fixation bias is a
      major predictor for human gaze allocation, which becomes more prominent with
      increased noise intensity. Our results indicate a crucial role of external noise
      intensity in determining scene-viewing gaze behaviour, which should be considered
      in the development of realistic human-vision-inspired attention models. 

PMID- 25982712
TI  - Material properties derived from three-dimensional shape representations.
AB  - Retinal image structure is due to a complex mixture of physical sources that
      includes the surface's 3D shape, light-reflectance and transmittance properties,
      and the light field. The visual system can somehow discriminate between these
      different sources of image structure and recover information about the objects
      and surfaces in the scene. There has been significant debate about the nature of
      the representations that are used to derive surface reflectance properties such
      as specularity (gloss). Specularity could be derived either directly from 2D
      image properties or by exploiting information that can only be derived from
      representations in which 3D shape has been made explicit. We recently provided
      evidence that 3D shape information can play a critical role in the perception of
      material specularity, but the shape manipulation in our prior study also
      significantly changed 2D image properties (Marlow, Todorovic, & Anderson, 2015).
      Here, we held fixed all monocularly visible 2D image properties and manipulated
      3D shape stereoscopically. When binocularly fused, the depicted 3D shapes induced
      striking transformations in the surfaces' apparent material properties, which
      vary from matte to 'metallic'. Our psychophysical measurements of perceived
      specularity reveal that 3D shape information can play a critical role in material
      perception for both singly-curved surfaces and more complex geometries that curve
      in two directions. These results provide strong evidence that the perception of
      material specularity can depend on physical constraints derived from
      representations in which three-dimensional shape has been made explicit. 

PMID- 25982713
TI  - Facilitatory mechanisms of specular highlights in the perception of depth.
AB  - We investigated whether specular highlights facilitate the perception of shape
      from shading in a search paradigm and how highlights interact with shading to
      facilitate this perception. Our results indicated that stimuli containing
      highlights led to shorter searching time with the dependence on the light source
      direction (top lights make searching faster), suggesting that highlights indeed
      facilitate shape-from-shading processing. To examine how highlight processing
      interacts with shading processing, we tested unnatural stimuli for which the
      lighting directions for shading and highlights were inconsistent. The results
      indicated that unnatural highlights (bright spots) placed in a direction
      inconsistent with the shading either decrease or do not alter searching time.
      This suggests that highlights may facilitate, and not suppress, shading
      processing. With more physically plausible highlights generated from image-based
      lighting, we also observed facilitation with consistent highlights, but no change
      with inconsistent highlights. Finally, we examined whether highlights indeed work
      to facilitate depth perception in a discrimination task. The results showed that
      correct discrimination of depth increases when highlights are added to shading
      even when their lighting directions are inconsistent. These results indicate that
      specular highlights facilitate shading processing, and do not suppress it even
      when the highlights are placed in a direction inconsistent with shading. The
      results also elucidate the lighting constraints of the visual system. 

PMID- 25982714
TI  - Dynamic composite faces are processed holistically.
AB  - Holistic processing is considered one of the hallmarks of face recognition.
      Recent studies using the composite task claim to show a lack of holistic
      processing for dynamic faces, however they only presented moving faces in the
      learning phase and tested with static composite images. So while previous
      research has addressed the question of whether moving faces influence the
      processing of subsequently viewed static faces, the question of whether moving
      faces are processed holistically remains unanswered. We address that question
      here. In our study participants learned faces in motion and were tested on moving
      composite faces, or learned static faces and were tested on static composite
      faces. We found a clear composite effect for both upright static and dynamic
      faces, with no significant difference in the magnitude of those effects. Further,
      there was no evidence of composite or motion effects in inverted conditions,
      ruling out low level or other motion signal properties as explanations of
      performance in upright faces. Together, these results show that upright moving
      faces are processed holistically, in a similar manner to static faces, extending
      decades of research with static faces and confirming the importance of holistic
      processing to familiar face recognition. 

PMID- 25982715
TI  - The art of braking: Post saccadic oscillations in the eye tracker signal decrease
      with increasing saccade size.
AB  - Recent research has shown that the pupil signal from video-based eye trackers
      contains post saccadic oscillations (PSOs). These reflect pupil motion relative
      to the limbus (Nystrom, Hooge, & Holmqvist, 2013). More knowledge about video
      based eye tracker signals is essential to allow comparison between the findings
      obtained from modern systems, and those of older eye tracking technologies (e.g.
      coils and measurement of the Dual Purkinje Image-DPI). We investigated PSOs in
      horizontal and vertical saccades of different sizes with two high quality video
      eye trackers. PSOs were very similar within observers, but not between observers.
      PSO amplitude decreased with increasing saccade size, and this effect was even
      stronger in vertical saccades; PSOs were almost absent in large vertical
      saccades. Based on this observation we conclude that the occurrence of PSOs is
      related to deceleration at the end of a saccade. That PSOs are saccade size
      dependent and idiosyncratic is a problem for algorithmic determination of saccade
      endings. Careful description of the eye tracker, its signal, and the procedure
      used to extract saccades is required to enable researchers to compare data from
      different eye trackers. 

PMID- 25982716
TI  - Perceptual grouping determines haptic contextual modulation.
AB  - Since the early phenomenological demonstrations of Gestalt principles, one of the
      major challenges of Gestalt psychology has been to quantify these principles.
      Here, we show that contextual modulation, i.e. the influence of context on target
      perception, can be used as a tool to quantify perceptual grouping in the haptic
      domain, similar to the visual domain. We investigated the influence of target
      flanker grouping on performance in haptic vernier offset discrimination. We
      hypothesized that when, despite the apparent differences between vision and
      haptics, similar grouping principles are operational, a similar pattern of
      flanker interference would be observed in the haptic as in the visual domain.
      Participants discriminated the offset of a haptic vernier. The vernier was
      flanked by different flanker configurations: no flankers, single flanking lines,
      10 flanking lines, rectangles and single perpendicular lines, varying the degree
      to which the vernier grouped with the flankers. Additionally, we used two
      different flanker widths (same width as and narrower than the target), again to
      vary target-flanker grouping. Our results show a clear effect of flankers:
      performance was much better when the vernier was presented alone compared to when
      it was presented with flankers. In the majority of flanker configurations,
      grouping between the target and the flankers determined the strength of
      interference, similar to the visual domain. However, in the same width
      rectangular flanker condition we found aberrant results. We discuss the results
      of our study in light of similarities and differences between vision and haptics
      and the interaction between different grouping principles. We conclude that in
      haptics, similar organization principles apply as in visual perception and argue
      that grouping and Gestalt are key organization principles not only of vision, but
      of the perceptual system in general.

PMID- 25982717
TI  - Clutter perception is invariant to image size.
AB  - Two experiments evaluated the effect of retinal image size on the proto-object
      model of visual clutter perception. Experiment 1 had 20 participants order 90
      small images of random-category real-world scenes from least to most cluttered.
      Aggregating these individual rankings into a single median clutter ranking and
      comparing it to a previously reported clutter ranking of larger versions of the
      identical scenes yielded a Spearman's rho=.953 (p<.001), suggesting that relative
      clutter perception is largely invariant to image size. We then applied the proto
      object model of clutter perception to these smaller images and obtained a clutter
      estimate for each. Correlating these estimates with the median behavioral ranking
      yielded a Spearman's rho=.852 (p<.001), which we showed in a comparative analysis
      to be better than six other methods of estimating clutter. Experiment 2
      intermixed large and small versions of the Experiment 1 scenes and had
      participants (n=18) again rank them for clutter. We found that median clutter
      rankings of these size-intermixed images were essentially the same as the small
      and large median rankings from Experiment 1, suggesting size invariance in
      absolute clutter perception. Moreover, the proto-object model again successfully
      captured this result. We conclude that both relative and absolute clutter
      perception is invariant to retinal image size. We further speculate that clutter
      perception is mediated by proto-objects-a preattentive level of visual
      representation between features and objects-and that using the proto-object model
      we may be able to glimpse into this pre-attentive world. 

PMID- 25982718
TI  - A comparison of spatial frequency tuning for judgments of eye gaze and facial
      identity.
AB  - Humans use the direction of eye gaze and facial identity to make important social
      judgments. We carried out the first measurements of spatial frequency (SF) tuning
      for judgments of eye gaze, and compared SF tuning for judgments of facial
      identity and eye gaze. In Experiment 1, participants discriminated between
      leftward and rightward shifts of gaze, or between two male faces or two female
      faces. Faces were masked with visual noise that blocked one of 10 SF bands. For
      each task and masking SF, we measured contrast thresholds for human observers,
      and used an ideal observer to measure the amount of visual information available
      to perform the task. As in previous research, low to mid SFs were most important
      for judgments of facial identity. Mid to high SFs were most important for
      judgments of eye gaze, and the highest SF important for these judgments was
      higher than that for identity. In Experiment 2, participants discriminated
      horizontal and vertical shifts of gaze. The highest SF important for judgments of
      gaze did not differ between the horizontal and vertical axes. However, SFs above
      and below this value were more important for judgments of vertical shifts of gaze
      than for horizontal shifts of gaze. These results suggest that the visual system
      relies on higher SFs for judgments of eye gaze than for judgments of facial
      identity, and that SF tuning is broader for judgments of vertical shifts of gaze
      than for horizontal shifts of gaze. 

PMID- 25982719
TI  - Assessing the precision of gaze following using a stereoscopic 3D virtual reality
      setting.
AB  - Despite the ecological importance of gaze following, little is known about the
      underlying neuronal processes, which allow us to extract gaze direction from the
      geometric features of the eye and head of a conspecific. In order to understand
      the neuronal mechanisms underlying this ability, a careful description of the
      capacity and the limitations of gaze following at the behavioral level is needed.
      Previous studies of gaze following, which relied on naturalistic settings have
      the disadvantage of allowing only very limited control of potentially relevant
      visual features guiding gaze following, such as the contrast of iris and sclera,
      the shape of the eyelids and--in the case of photographs--they lack depth. Hence,
      in order to get full control of potentially relevant features we decided to study
      gaze following of human observers guided by the gaze of a human avatar seen
      stereoscopically. To this end we established a stereoscopic 3D virtual reality
      setup, in which we tested human subjects' abilities to detect at which target a
      human avatar was looking at. Following the gaze of the avatar showed all the
      features of the gaze following of a natural person, namely a substantial degree
      of precision associated with a consistent pattern of systematic deviations from
      the target. Poor stereo vision affected performance surprisingly little (only in
      certain experimental conditions). Only gaze following guided by targets at larger
      downward eccentricities exhibited a differential effect of the presence or
      absence of accompanying movements of the avatar's eyelids and eyebrows.

PMID- 25982721
TI  - Neuromodulation of the Cervical Dorsal Root Ganglion for Upper Extremity Complex
      Regional Pain Syndrome-Case Report.
AB  - OBJECTIVE: Targeting the dorsal column, spinal cord stimulation (SCS) serves as a
      treatment method for complex regional pain syndrome (CRPS). Certain anatomical
      pain distributions are difficult to treat with traditional SCS, including the
      distal extremities. We present a case where stimulation of the dorsal root
      ganglion (DRG) was performed to treat CRPS in the distal upper extremity. CASE
      REPORT: A 43-year-old female underwent a right elbow arthroscopy with open
      reduction and internal fixation after sustaining a radial head fracture. Several
      months after her surgery, she experienced hyperesthesia, skin color changes,
      decreased range of motion, weakness distal to the right olecranon, and was
      diagnosed with CRPS. Aggressive physical therapy, nonsteroidal anti-inflammatory
      drugs (NSAIDs), and neuropathic agents provided mild relief. Open capsular
      release, hardware removal, and chondral debridement of the elbow did not provide
      alleviation. A diagnostic stellate ganglion block provided complete relief for
      two weeks. A therapeutic block allowed one day of relief, followed by recurrence
      of her symptoms. She underwent an SCS trial for treatment. Scar tissue in the
      posterior epidural space prevented catheter advancement, causing it to exit the
      C6 foramen. Incidental stimulation of the DRG occurred. RESULTS: On follow-up,
      patient reported >70% relief of her pain. On the visual analog scale, her maximal
      pain decreased from 8/10 to 4/10, with resolution of her initial symptoms and
      ability to perform all of her activities of daily living. CONCLUSION: To our
      knowledge, this is the only reported case of utilizing DRG stimulation for CRPS
      of the distal upper extremity. Neuromodulation of the DRG appears to be an
      effective option for targeting painful areas in CRPS.

PMID- 25982720
TI  - Defibrillator implantations for primary prevention in the United States:
      Inappropriate care or inadequate documentation: Insights from the National
      Cardiovascular Data ICD Registry.
AB  - BACKGROUND: Prior studies have reported that more than 20% of implantable
      cardioverter-defibrillator (ICD) implantations in the United States do not adhere
      to trial-based criteria. OBJECTIVE: We sought to investigate the patient
      characteristics associated with not meeting the inclusion criteria of the
      clinical trials that have demonstrated the efficacy of primary prevention ICDs.
      METHODS: Using data from the National Cardiovascular Data Registry's ICD
      Registry, we identified patients who received ICDs for primary prevention from
      January 2006 to December 2008. We determined whether patients met the inclusion
      criteria of at least 1 of the 4 ICD primary prevention trials: Multicenter
      Automatic Defibrillator Implantation Trial (MADIT), MADIT-II, Sudden Cardiac
      Death in Heart Failure Trial (SCD-HeFT), and the Multicenter Unsustained
      Tachycardia Trial (MUSTT). RESULTS: Among 150,264 patients, 86% met criteria for
      an ICD implantation based on trial data. The proportion of patients who did not
      meet trial-based criteria increased as age decreased. In multivariate analysis,
      the significant predictors for not meeting trial criteria included prior cardiac
      transplantation (odds ratio [OR] 2.1), pediatric electrophysiology operator (OR
      2.0), and high-grade atrioventricular conduction disease (OR 1.4). CONCLUSION:
      Among National Cardiovascular Data Registry registrants receiving first-time ICDs
      for primary prevention, the majority met trial-based criteria. Multivariate
      analyses suggested that many patients who did not meet the trial-based criteria
      may have had clinical circumstances that warranted ICD implantation. These
      findings caution against the use of trial-based indications to determine site
      quality metrics that could penalize sites that care for younger patients. The
      planned incorporation of appropriate use criteria into the ICD registry may
      better characterize patient- and site-level quality and performance.

PMID- 25982722
TI  - An ultrasensitive squamous cell carcinoma antigen biosensing platform utilizing
      double-antibody single-channel amplification strategy.
AB  - A novel electrochemical immunosensor was developed for ultrasensitive detection
      of squamous cell carcinoma antigen (SCCA), which was based on the double-antibody
      single-channel amplification strategy. For the first time, human immunoglobulin
      antibody (anti-HIgG) was used as the supporting framework to amplify the loading
      quantity of SCCA antibody (anti-SCCA). In this strategy, SCCA can be detected
      without using mesoporous nanometers to amplify the signal. In addition, Pd
      icosahedrons were first used as the connecter to immobilize the antibodies and
      strengthen the sensitivity. Only one touch point exists under the limited
      condition between a sphere and another shape in geometry, thus the Pd icosahedron
      is an excellent candidate as the role of connecter. Gold nanoparticles (Au NPs)
      decorated with mercapto-functionalized graphene sheets (Au@GS) were synthesized
      as the transducing materials. The fabricated immunosensor exhibited an excellent
      detection limit of 2.8 pg/mL and wide linear range of 0.01-5 ng/mL. This kind of
      immunosensor would provide a potential application in clinical diagnosis.

PMID- 25982723
TI  - New biosensor for detection of copper ions in water based on immobilized
      genetically modified yeast cells.
AB  - Contamination of water by heavy metals represents a potential risk for both
      aquatic and terrestrial organisms, including humans. Heavy metals in water
      resources can come from various industrial activities, and drinking water can be
      ex-post contaminated by heavy metals such as Cu(2+) from house fittings (e.g.,
      water reservoirs) and pipes. Here, we present a new copper biosensor capable of
      detecting copper ions at concentrations of 1-100 MUM. This biosensor is based on
      cells of a specifically modified Saccharomyces cerevisiae strain immobilized in
      alginate beads. Depending on the concentration of copper, the biosensor beads
      change color from white, when copper is present in concentrations below the
      detection limit, to pink or red based on the increase in copper concentration.
      The biosensor was successfully tested in the determination of copper
      concentrations in real samples of water contaminated with copper ions. In
      contrast to analytical methods or other biosensors based on fluorescent proteins,
      the newly designed biosensor does not require specific equipment and allows the
      quick detection of copper in many parallel samples.

PMID- 25982724
TI  - Towards intrinsic graphene biosensor: A label-free, suspended single crystalline
      graphene sensor for multiplex lung cancer tumor markers detection.
AB  - Graphene biosensors reported so far are based on polycrystalline graphene flakes
      which are anchored on supporting substrates. The influence of grain boundary and
      the scattering from substrate drastically degrade the properties of graphene and
      conceal the performance of intrinsic graphene as a sensor. Here we report a label
      free biosensor based on suspended single crystalline graphene (SCG), which can
      get rid of grain boundary and substrate scattering, revealing the biosensing
      mechanism of intrinsic graphene for the first time. Monolayer SCG flakes were
      derived from low pressure chemical vapor deposition (LPCVD) method. Multiplex
      detection of three different lung cancer tumor markers was realized. The
      suspended structure can largely improve the sensitivity and detection limit (0.1
      pg/ml) of the sensor, and the single crystalline nature of SCG enable the
      biosensor to have superior uniformity compared to polycrystalline ones. The SCG
      sensors exhibit superb specificity and large linear detection range from 1 pg/ml
      to 1 MUg/ml, showing the prominent advantages of graphene as a sensing material.

PMID- 25982725
TI  - An ultrasensitive DNA biosensor based on covalent immobilization of probe DNA on
      fern leaf-like alpha-Fe2O3 and chitosan Hybrid film using terephthalaldehyde as
      arm-linker.
AB  - In this work, a novel electrochemical DNA biosensor has been developed based on
      the hybrid film of fern leaf-like alpha-Fe2O3 microparticles and chitosan (CS).
      The fern leaf-like alpha-Fe2O3 microparticles were synthesized via a facile
      template-free hydrothermal method, and their morphologies were characterized by X
      ray diffraction, energy dispersive spectrometry, scanning electron microscope,
      and transmission electron microscope. Electrochemical characterization assays
      revealed that the hybrid film modified electrode had remarkable synergistic
      effects of the large accessible surface area and high electrical conductivity of
      semiconductive Fe2O3, and the good film stability of CS. Based on the rich amino
      groups on CS, the CS-Fe2O3 hybrid film was employed as a functional matrix for
      probe DNA immobilization using terephthalaldehyde (TPA) as a bifunctional arm
      linker. The hybridization capacity of the developed biosensor was evaluated with
      electrochemical impedance spectroscopy (EIS) using [Fe(CN)6](3-/4-) as the
      indicating probe. A wide dynamic detection range from 1.0 * 10(-14) to 1.0 * 10(
      10)M with ultralow detection limit of 5.6 * 10(-15)M was achieved for the target
      DNA. The hybridization selectivity experiments further revealed that the
      biosensor could discriminate fully complementary sequences from one-base
      mismatched, three-base mismatched, and non-complementary sequences. Moreover, the
      biosensor showed the advantage of good regeneration ability and reproducibility.

PMID- 25982726
TI  - Novel multifunction-integrated molecular beacon for the amplification detection
      of DNA hybridization based on primer/template-free isothermal polymerization.
AB  - Molecular beacon (MB) is widely explored as a signaling probe in powerful
      biosensing systems, for example, enzyme-assisted strand displacement
      amplification (SDA)-based system. The existing polymerization-based amplification
      system is often composed of recognition element, primer, template and
      fluorescence reporter. To develop a new MB sensing system and simply the signal
      amplification design, we herein attempted to propose a multifunctional integrated
      MB (MI-MB) for the polymerization amplification detection of target DNA via
      introducing a G-rich fragment into the loop of MB without using any exogenous
      auxiliary oligonucleotide probe. Utilizing only one MI-MB probe, the p53 target
      gene could trigger the cycles of hybridization/polymerization/displacement,
      resulting in amplification of the target hybridization event. Thus, the p53 gene
      can be detected down to 5 * 10(-10)M with the linear response range from 5 * 10(
      10)M to 4 * 10(-7)M. Using the MI-MB, we could readily discriminate the point
      mutation-contained p53 from the wild-type one. As a proof-of-concept study, owing
      to its simplicity and multifunction, including recognition, replication,
      amplification and signaling, the MI-MB exhibits the great potential for the
      development of different biosensors for various biomedical applications,
      especially, for early cancer diagnosis.

PMID- 25982727
TI  - DNA nanostructures based biosensor for the determination of aromatic compounds.
AB  - Graphite electrode was modified using multi-walled carbon nanotubes (MWCNT),
      chitosan (CS), glutaraldehyde (GTA) and DNA nanostructures (nsDNA). DNA
      nanostructures of 50 nm in size were produced from single DNA template sequence
      using a simple two step procedure and were confirmed using TEM and AFM analysis.
      The modified electrode was applied to the electrochemical detection of aromatic
      compounds using EIS. The modified electrode was characterized using differential
      pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS) and cyclic
      voltammetry (CV). For comparison, electrochemical results derived from single
      stranded (50 bp length) and double stranded (50 bp length) DNA based biosensors
      were used. The results indicate that the modified electrode prior to nsDNA
      immobilization provides a viable platform that effectively promotes electron
      transfer between nsDNA and the electrode. The mode of binding between the nsDNA
      and aromatic compounds was investigated using EIS, indicating that the dominant
      interaction is non-covalent. nsDNA based biosensor was observed to act as an
      efficient biosensor in selective and sensitive identification of aromatic
      compounds.

PMID- 25982728
TI  - Label-free detection of ApoE4-mediated beta-amyloid aggregation on single
      nanoparticle uncovering Alzheimer's disease.
AB  - Beta amyloid (Abeta) deposition is a pathological milestone of Alzheimer's
      disease (AD). This is facilitated by an isoform of Apolipoprotein E4 (ApoE4),
      which is a dominant risk factor for AD. However, current in vitro Abeta
      aggregation assays were performed in extreme conditions not linked to
      physiological conditions, to understand the mechanism of Abeta induced
      neurotoxicity. Here, we present a simple method for the ApoE4-mediated Abeta
      aggregation at physiological conditions using single gold nanoparticle based on
      localized surface plasmon resonance (LSPR). It can be directly observed by dark
      field microscope or even by the naked eye. Following LSPR principles, we used
      ApoE4 inducing Abeta42 self-assemblies on gold nanoparticles (AuNPs) surface via
      their surface charge interaction. Using physiologically mimic cerebrospinal
      fluid, we determined a detection limit of 1.5 pM for Abeta42 corresponding to the
      ~2.9 nm LSPR-peak shift under ApoE4. Interestingly, the result also shows that
      ApoE4 induces the aggregation of Abeta42 more specifically and rapidly than that
      of Abeta40. This is the first biomimetic platform for real-time detection of
      Abeta aggregation, mimicking biological conditions, which can be used to
      investigate AD directly.

PMID- 25982729
TI  - General approach for electrochemical detection of persistent pharmaceutical
      micropollutants: Application to acetaminophen.
AB  - We propose in this work a general and versatile methodology for electrochemical
      monitoring of persistent pharmaceutical micropollutants. The system presented is
      based on an electroactive and electropolymerized hapten (mimetic molecule of the
      pollutant to be detected) and a specific antibody that competitively binds either
      the hapten or the pollutant. The current delivered by the device depends on this
      competitive equilibrium and therefore on the pollutant's concentration. The
      determination of the pharmaceutical product operates within minutes, using square
      wave voltammetry without labeling or addition of a reactant in solution; the
      competitive hapten/antibody transduction produces a "signal-on" (a current
      increase). Applied to acetaminophen, this electrochemical immunosensor presents a
      very low detection limit of ca. 10 pM, (S/N=3) and a very high selectivity
      towards structural analogs (aspirin, BPA, and piperazine) even in a mixture.

PMID- 25982730
TI  - Facile electrochemical detection of botulinum neurotoxin type E using a two-step
      proteolytic cleavage.
AB  - Facile electrochemical methods for measuring protease concentration or protease
      activity are essential for point-of-care testing of toxic proteases. However,
      electrochemical detection of proteases, such as botulinum neurotoxin type E
      (BoNT/E), that cleave a peptide bond between two specific amino acid residues is
      challenging. This study reports a facile and sensitive electrochemical method for
      BoNT/E detection. The method is based on a two-step proteolytic cleavage using a
      target BoNT/E light chain (BoNT/E-LC) and an externally supplemented
      exopeptidase, L-leucine-aminopeptidase (LAP). BoNT/E-LC cleaves a peptide bond
      between arginine and isoleucine in IDTQNRQIDRI-4-amino-1-naphthol (oligopeptide
      AN) to generate isoleucine-AN. Subsequently, LAP cleaves a bond between
      isoleucine and AN to liberate a free electroactive AN species. The liberated AN
      participates in electrochemical-chemical-chemical (ECC) redox cycling involving
      Ru(NH3)6(3+), AN, and a reducing agent, which allows a high signal amplification.
      Electrochemical detection is carried out without surface modification of indium
      tin oxide electrodes. We show that dithiothreitol is beneficial for enhancing the
      enzymatic activity of BoNT/E-LC and also for achieving a fast ECC redox cycling.
      An incubation temperature of 37 degrees C and the use of phosphate buffered
      saline (PBS) buffer resulted in optimal signal-to-background ratios for efficient
      BoNT/E detection. BoNT/E-LC could be detected at concentrations of approximately
      2.0 pg/mL, 0.2, and 3 ng/mL after 4h, 2h, and 15 min incubation in PBS buffer,
      respectively, and approximately 0.3 ng/mL after 2-h incubation in bottled water.
      The method developed could be applied in fast, sensitive, and selective detection
      of any protease that cleaves a peptide bond between two specific amino acid
      residues.

PMID- 25982731
TI  - Enhancement of antibacterial properties of silver nanoparticles-ceftriaxone
      conjugate through Mukia maderaspatana leaf extract mediated synthesis.
AB  - Green synthesis of nanoparticles with low range of toxicity and conjugation to
      antibiotics has become an attractive area of research for several biomedical
      applications. Nanoconjugates exhibited notable increase in biological activity
      compared to free antibiotic molecules. With this perception, we report the
      biosynthesis of silver nanoparticles using aqueous extract of leaves of Mukia
      maderaspatana and subsequent conjugation of the silver nanoparticles to
      antibiotic ceftriaxone. The leaves of this plant are known to be a rich source of
      phenolic compounds with high antioxidant activity that are used as reducing
      agents. The size, morphology, crystallinity, composition of the synthesized
      silver nanoparticles and conjugation of ceftriaxone to silver nanoparticles were
      studied using analytical techniques. The activity of the conjugates against
      Bacillus subtilis (MTCC 1790), Klebsiella pneumoniae (MTCC 3384), Staphylococcus
      aureus (ATCC 25923), and Salmonella typhi (MTCC 3224) was compared to ceftriaxone
      and unconjugated nanoparticles using disc diffusion method. The effect of silver
      nanoparticles on the reduction of biofilms of Pseudomonas fluorescens (MTCC 6732)
      was determined by micro plate assay method. The antioxidant activities of
      extract, silver nitrate, silver nanoparticles, ceftriaxone and conjugates of
      nanoparticles were evaluated by radical scavenging 1, 1- diphenyl-2
      picrylhydrazyl test. Ultraviolet visible spectroscopy and Fourier transform
      infrared spectroscopy confirmed the formation of metallic silver nanoparticles
      and conjugation to ceftriaxone. Atomic force microscopy, transmission electron
      microscopy and particle size analysis showed that the formed particles were of
      spherical morphology with appreciable nanosize and the conjugation was confirmed
      by slight increase in surface roughness. The results thus showed that the
      conjugation of ceftriaxone with silver nanoparticles has better antioxidant and
      antimicrobial effects than ceftriaxone and unconjugated nanoparticles. It can be
      suggested that M. maderaspatana mediated nanoparticle-ceftriaxone conjugate can
      be used effectively in the production of potential antioxidant and antimicrobial
      agents. The present study offers a significant overview to the development of
      novel antimicrobial nanoparticles. 

PMID- 25982732
TI  - PathRings: a web-based tool for exploration of ortholog and expression data in
      biological pathways.
AB  - BACKGROUND: High-throughput methods are generating biological data on a vast
      scale. In many instances, genomic, transcriptomic, and proteomic data must be
      interpreted in the context of signaling and metabolic pathways to yield testable
      hypotheses. Since humans can interpret visual information rapidly, a means for
      interactive visual exploration that lets biologists interpret such data in a
      comprehensive and exploratory manner would be invaluable. However, humans have
      limited memory capacity. Current visualization tools have limited viewing and
      manipulation capabilities to address complex data analysis problems, and visual
      exploratory tools are needed to reduce the high mental workload imposed on
      biologists. RESULTS: We present PathRings, a new interactive web-based, scalable
      biological pathway visualization tool for biologists to explore and interpret
      biological pathways. PathRings integrates metabolic and signaling pathways from
      Reactome in a single compound graph visualization, and uses color to highlight
      genes and pathways affected by input data. Pathways are available for multiple
      species and analysis of user-defined species or input is also possible. PathRings
      permits an overview of the impact of gene expression data on all pathways to
      facilitate visual pattern finding. Detailed pathways information can be opened in
      new visualizations while maintaining the overview, that form a visual exploration
      provenance. A dynamic multi-view bubbles interface is designed to support
      biologists' analytical tasks by letting users construct incremental views that
      further reflect biologists' analytical process. This approach decomposes complex
      tasks into simpler ones and automates multi-view management. CONCLUSIONS:
      PathRings has been designed to accommodate interactive visual analysis of
      experimental data in the context of pathways defined by Reactome. Our new
      approach to interface design can effectively support comparative tasks over
      substantially larger collection than existing tools. The dynamic interaction
      among multi-view dataset visualization improves the data exploration. PathRings
      is available free at http://raven.anr.udel.edu/~sunliang/PathRings and the source
      code is hosted on Github: https://github.com/ivcl/PathRings .

PMID- 25982733
TI  - Occurrence and risk assessment of pharmaceuticals and personal care products and
      endocrine disrupting chemicals in reclaimed water and receiving groundwater in
      China.
AB  - Groundwater recharge using reclaimed water is considered a promising method to
      alleviate groundwater depletion. However, pollutants in reclaimed water could be
      recharged into groundwater during this process, thereby posing a risk to
      groundwater and human health. In this study, 12 cities in northern China were
      selected for reclaimed water and groundwater sampling. Analysis of the samples
      revealed the presence of nine pharmaceutical and personal care products (PPCPs)
      and five endocrine disrupting compounds (EDCs). In reclaimed water, all the PPCPs
      and EDCs were found, with sulpiride (SP) and estriol (E3) being most frequently
      detected. In groundwater samples, only ketoprofen (KP), mefenamic acid (MA),
      nalidixic acid (NA) and SP were detected among PPCPs, while bisphenol-A (BPA) was
      dominant among the target EDCs. The risk quotients (RQs) of all target PPCPs and
      EDCs except 17alpha-ethinyl estradiol (EE2) and E3 were below 1 in groundwater
      samples, indicating that EE2 and E3 deserve priority preferential treatment
      before recharging. 

PMID- 25982734
TI  - A lucrative technique to reduce Ni toxicity in Raphanus sativus plant by
      phosphate amendment: Special reference to plant metabolism.
AB  - Nickel (Ni) contamination is one of the serious environmental problems. It
      creates hazard in soil environment and also in crop quality. In the present
      study, response of Raphanus sativus (radish) to Ni (50mgkg(-1) soil) under
      different concentrations (100, 200, 500 and 1000 DAPmgkg(-1) soil) of phosphate
      as soil amendment was investigated after 40 days of growth. Ni-treated plants
      without amendment showed reduction in their growth as a result of appreciable
      decrease in the photosynthetic activity. Under this treatment, Ni accumulation
      significantly enhanced lipid peroxidation and level of oxidants showing oxidative
      stress and it was also associated with decrease in the activities of
      antioxidative enzymes except super oxide dismutase (SOD). Application of
      phosphate in Ni contaminated soil resulted into significant improvement in plant
      growth. Under phosphate amendment, the status of oxidative biomarkers: SOR, TBARS
      and H2O2 were under control by the higher activity of antioxidants: APX, CAT,
      POD, GST and DHAR compared to Ni contaminated soil without amendment. Principal
      component analysis (PCA) was performed to show the significant changes in
      biochemical traits under control and phosphate amendment. The values of PS II
      transient kinetics: Phi-E0, Psi-0 and PIABS increased and values of energy
      fluxes: ABC/RC, Tro/RC, Eto/RC and Dio/RC decreased in plants grown in Ni
      contaminated soil under phosphate amendment as compared to without amendment.
      Among all doses of phosphate amendment soil amended at 500mg DAPkg(-)(1) soil the
      yield of plant was the highest and Ni accumulation was the lowest. As compared to
      plants grown in Ni treated soil without amendment the yield of plant at 500mg
      DAPkg(-1) soil showed about 70% increment and the reduction in Ni accumulation
      was 63% in shoot and 64% in root. Because of these beneficial effects this
      technique can be easily applied at metal contaminated agricultural fields to
      reduce food chain contamination and to improve food quality. 

PMID- 25982736
TI  - Conformation of poly(ethylene oxide) dissolved in the solvate ionic liquid
      [Li(G4)]TFSI.
AB  - The conformation of 38 kDa PEO in a solvate ionic liquid (SIL), lithium
      tetraglyme bis(trifluoromethane-sulfonyl)amide ([Li(G4)]TFSI) from dilute to
      concentrated solution regimes has been determined by small angle neutron
      scattering and rheology. SANS analysis reveals that [Li(G4)]TFSI is better than a
      theta solvent (theta-good) for PEO. The variation of the radius of gyration (Rg)
      and viscosity as a function of polymer concentration allow the overlap
      concentrations, c* and c**, to be identified at 13 mg mL(-1) and 50 mg mL(-1),
      respectively, which are similar to values reported previously for conventional
      ionic liquids. Unlike water and conventional ionic liquids, [Li(G4)]TFSI cannot
      form hydrogen bonds with PEO. Thermal gravimetric analysis indicates that the
      solvation of PEO by [Li(G4)]TFSI is a consequence of PEO forming coordinate bonds
      with the lithium by displacing the anion, but without displacing the glyme
      molecule. 

PMID- 25982735
TI  - Travel distances, socioeconomic characteristics, and health disparities in
      nonurgent and frequent use of Hospital Emergency Departments in South Carolina: a
      population-based observational study.
AB  - BACKGROUND: Nonurgent use of hospital emergency departments (ED) is a
      controversial topic. It is thought to increase healthcare costs and reduce
      quality, but is also considered a symptom of unequal access to health care. In
      this article, we investigate whether convenience (as proxied by travel distances
      to the hospital ED and to the closest federally qualified health center) is
      associated with nonurgent ED use, and whether evidence of health disparities
      exist in the way vulnerable populations use the hospital ED for medical care in
      South Carolina. METHODS: Our data includes 6,592,501 ED visits in South Carolina
      between 2005 and 2010 from the South Carolina Budget Control Board and Office of
      Research and Statistics. All ED visits by South Carolina residents with unmasked
      variables and nonmissing urgency measures, or approximately 76% of all ED visits,
      are used in the analysis. We perform multivariable linear regressions to estimate
      correlations between (1) travel distances and observable sociodemographic
      characteristics and (2) measures of nonurgent ED use or frequent nonurgent ED
      use, as defined by the New York University ED Algorithm. RESULTS: Patients with
      commercial private insurance, self-pay patients, and patients with other payment
      sources have lower measures of nonurgent ED use the further away the ED facility
      is from the patients' home address. Vulnerable populations, particularly African
      American and Medicaid patients, have higher measures of nonurgent ED scores, and
      are more frequent users of the ED for both nonurgent and urgent reasons in South
      Carolina. At the same time, African Americans visit the hospital ED for medical
      conditions with higher primary care-preventable scores. CONCLUSIONS: Contrary to
      popular belief, convenient access (in terms of travel distances) to hospital ED
      is correlated with less-urgent ED use among privately insured patients and self
      pay patients in South Carolina, but not publicly insured patients. Unequal access
      to primary care appears to exist, as suggested by African American patients' use
      of the hospital ED for primary care-treatable conditions while experiencing more
      frequent and more severe primary care-preventable conditions.

PMID- 25982737
TI  - Multiscale entropy analysis of resting-state magnetoencephalogram with tensor
      factorisations in Alzheimer's disease.
AB  - Tensor factorisations have proven useful to model amplitude and spectral
      information of brain recordings. Here, we assess the usefulness of tensor
      factorisations in the multiway analysis of other brain signal features in the
      context of complexity measures recently proposed to inspect multiscale dynamics.
      We consider the "refined composite multiscale entropy" (rcMSE), which computes
      entropy "profiles" showing levels of physiological complexity over temporal
      scales for individual signals. We compute the rcMSE of resting-state
      magnetoencephalogram (MEG) recordings from 36 patients with Alzheimer's disease
      and 26 control subjects. Instead of traditional simple visual examinations, we
      organise the entropy profiles as a three-way tensor to inspect relationships
      across temporal and spatial scales and subjects with multiway data analysis
      techniques based on PARAFAC and PARAFAC2 factorisations. A PARAFAC2 model with
      two factors was appropriate to account for the interactions in the entropy tensor
      between temporal scales and MEG channels for all subjects. Moreover, the PARAFAC2
      factors had information related to the subjects' diagnosis, achieving a cross
      validated area under the ROC curve of 0.77. This confirms the suitability of
      tensor factorisations to represent electrophysiological brain data efficiently
      despite the unsupervised nature of these techniques. This article is part of a
      Special Issue entitled 'Neural data analysis'.

PMID- 25982738
TI  - Embryology of Phyllonoma (Phyllonomaceae, Aquifoliales): characteristics and
      character evolution.
AB  - Phyllonoma, the sole genus of Phyllonomaceae (Aquifoliales) consisting of four
      Central American species, has not been well-characterized morphologically.
      Following a previous study of flower and inflorescence morphology, I here report
      the embryology of the genus based on P. tenuidens and compare its characteristics
      with those of other aquifolialean families, namely, Aquifoliaceae,
      Cardiopteridaceae, Helwingiaceae, and Stemonuraceae. Comparisons indicate that
      although Phyllonoma resembles all the other families embryologically, it more
      closely resembles Aquifoliaceae and Helwingiaceae in lacking a vascular bundle in
      its integument and bearing ab initio Cellular endosperm. The genus especially
      resembles Helwingiaceae by possessing a tenuinucellate ovule. This result
      corroborates molecular and floral morphological evidence, supporting the
      distinctness of Phyllonoma as a family and its sister-group relationship to East
      Asian Helwingiaceae. However, Phyllonoma is clearly distinguished from
      Helwingiaceae by seed coat structure. In Phyllonoma, the seeds (dispersed in
      berries) have a thick seed coat composed of irregularly enlarged, thick-walled
      exotestal cells, whereas the seeds (dispersed in drupes) have a thin membranous
      seed coat in Helwingiaceae. Taken together with earlier information on
      pollination (entomophily in Phyllonoma versus ambophily in Helwingiaceae),
      embryological evidence shows that distinct evolution has occurred in reproductive
      characters relating to pollination and seed dispersal in Phyllonoma. 

PMID- 25982739
TI  - Endophytic colonization of barley (Hordeum vulgare) roots by the nematophagous
      fungus Pochonia chlamydosporia reveals plant growth promotion and a general
      defense and stress transcriptomic response.
AB  - Plant crop yields are negatively conditioned by a large set of biotic and abiotic
      factors. An alternative to mitigate these adverse effects is the use of fungal
      biological control agents and endophytes. The egg-parasitic fungus Pochonia
      chlamydosporia has been traditionally studied because of its potential as a
      biological control agent of plant-parasitic nematodes. This fungus can also act
      as an endophyte in monocot and dicot plants, and has been shown to promote plant
      growth in different agronomic crops. An Affymetrix 22K Barley GeneChip was used
      in this work to analyze the barley root transcriptomic response to P.
      chlamydosporia root colonization. Functional gene ontology (GO) and gene set
      enrichment analyses showed that genes involved in stress response were enriched
      in the barley transcriptome under endophytism. An 87.5% of the probesets
      identified within the abiotic stress response group encoded heat shock proteins.
      Additionally, we found in our transcriptomic analysis an up-regulation of genes
      implicated in the biosynthesis of plant hormones, such as auxin, ethylene and
      jasmonic acid. Along with these, we detected induction of brassinosteroid
      insensitive 1-associated receptor kinase 1 (BR1) and other genes related to
      effector-triggered immunity (ETI) and pattern-triggered immunity (PTI). Our study
      supports at the molecular level the growth-promoting effect observed in plants
      endophytically colonized by P. chlamydosporia, which opens the door to further
      studies addressing the capacity of this fungus to mitigate the negative effects
      of biotic and abiotic factors on plant crops.

PMID- 25982741
TI  - Purification and characterization of halo-alkali-thermophilic protease from
      Halobacterium sp. strain HP25 isolated from raw salt, Lake Qarun, Fayoum, Egypt.
AB  - A total of 33 halophilic protease producers were isolated from different salt
      samples collected from Emisal salt company at Lake Qarun, Fayoum, Egypt. Of these
      strains, an extremely halophilic strain that grew optimally at 30 % (w/v) NaCl
      was characterized and identified as Halobacterium sp. strain HP25 based on 16S
      rRNA gene sequencing and phenotypic characterization. A halo-alkali-thermophilic
      protease was purified in three successive steps from the culture supernatant. The
      purified halophilic protease consisted of a single polypeptide chain with a
      molecular mass of 21 kDa and was enriched 167-fold to a specific activity of 6350
      U mg(-1). The purified enzyme was active over a broad pH range from 6.0 to 11.0,
      with maximum activity at pH 8.0, exhibited a broad temperature range from 30 to
      80  degrees C with optimum activity at 60  degrees C, and was active at salt
      concentrations ranging from 5 to 25 % (w/v), with optimum activity at 17 % NaCl
      (w/v). The K M and V max values of the purified halophilic protease with casein
      as a substrate were 523 ug mL(-1) and 2500 ug min(-1) mL(-1), respectively. In
      addition, this enzyme was stable in the tested organic solvents and laundry
      detergents such methanol, propanol, butanol, hexane, Persil and Ariel. The
      unusual properties of this enzyme allow it to be used for various applications,
      such as the ripening of salted fish. Furthermore, its stability and activity in
      the presence of organic solvents and detergents also allow the use of this enzyme
      for further novel applications and as an additive in detergent formulations.

PMID- 25982740
TI  - Increases of heat shock proteins and their mRNAs at high hydrostatic pressure in
      a deep-sea piezophilic bacterium, Shewanella violacea.
AB  - When non-extremophiles encounter extreme environmental conditions, which are
      natural for the extremophiles, stress reactions, e.g., expression of heat shock
      proteins (HSPs), are thought to be induced for survival. To understand how the
      extremophiles live in such extreme environments, we studied the effects of high
      hydrostatic pressure on cellular contents of HSPs and their mRNAs during growth
      in a piezophilic bacterium, Shewanella violacea. HSPs increased at high
      hydrostatic pressures even when optimal for growth. The mRNAs and proteins of
      these HSPs significantly increased at higher hydrostatic pressure in S. violacea.
      In the non-piezophilic Escherichia coli, however, their mRNAs decreased, while
      their proteins did not change. Several transcriptional start sites (TSSs) for HSP
      genes were determined by the primer extension method and some of them showed
      hydrostatic pressure-dependent increase of the mRNAs. A major refolding target of
      one of the HSPs, chaperonin, at high hydrostatic pressure was shown to be RplB, a
      subunit of the 50S ribosome. These results suggested that in S. violacea, HSPs
      play essential roles, e.g., maintaining protein complex machinery including
      ribosomes, in the growth and viability at high hydrostatic pressure, and that, in
      their expression, the transcription is under the control of sigma(32). 

PMID- 25982742
TI  - The phylogeny and evolutionary history of the Lesion Simulating Disease (LSD)
      gene family in Viridiplantae.
AB  - The Lesion Simulating Disease (LSD) genes encode a family of zinc finger proteins
      that play a role in programmed cell death (PCD) and other biological processes,
      such as plant growth and photosynthesis. In the present study, we report the
      reconstruction of the evolutionary history of the LSD gene family in
      Viridiplantae. Phylogenetic analysis revealed that the monocot and eudicot genes
      were distributed along the phylogeny, indicating that the expansion of the family
      occurred prior to the diversification between these clades. Sequences encoding
      proteins that present one, two, or three LSD domains formed separate groups. The
      secondary structure of these different LSD proteins presented a similar
      composition, with the beta-sheets being their main component. The evolution by
      gene duplication was identified only to the genes that contain three LSD domains,
      which generated proteins with equal structure. Moreover, genes encoding proteins
      with one or two LSD domains evolved as single-copy genes and did not result from
      loss or gain in LSD domains. These results were corroborated by synteny analysis
      among regions containing paralogous/orthologous genes in Glycine max and Populus
      trichocarpa. The Ka/Ks ratio between paralogous/orthologous genes revealed that a
      subfunctionalization process possibly could be occurring with the LSD genes,
      explaining the involvement of LSD members in different biological processes, in
      addition to the negative regulation of PCD. This study presents important novelty
      in the evolutionary history of the LSD family and provides a basis for future
      research on individual LSD genes and their involvement in important pathway
      networks in plants. 

PMID- 25982743
TI  - Inheritance of Pantoea type III secretion systems through both vertical and
      horizontal transfer.
AB  - The type III secretion system (T3SS) is an extracellular apparatus used by many
      Gram-negative bacteria to deliver effector proteins directly into plant and
      animal cells, thereby facilitating host-specific association. Strains of the
      enterobacterial genus, Pantoea, have been isolated from a wide variety of hosts,
      including plants, insects, and humans, yet it is unclear whether the T3SS may be
      involved in these associations. In this study, we use comparative genomics and
      phylogenetic methods to examine the origin and distribution of T3SSs in 35
      sequenced environmental and clinical strains of Pantoea. We began our analysis by
      examining the distribution of the previously characterized plant cell-specific
      PSI-1 and animal cell-specific PSI-2 of the plant pathogenic Pantoea stewartii
      subsp. stewartii DC283 (PstDC283), and showed that both had a somewhat limited
      distribution. Our analysis, however, identified two variants of a unique plant
      cell-specific T3SS (PSI-1a and PSI-1b) in six Pantoea strains, including a
      clinical isolate. Our genome analysis of PstDC283 also identified a third T3SS
      that we named PSI-3, which has a similar genetic content and organization to the
      Salmonella, animal cell-specific SPI-2 system. Phylogenetic analysis of all three
      systems suggests that the PSI-1 system has been inherited vertically, whereas the
      newly identified PSI-1a and PSI-1b systems have been acquired independently from
      other genera within the Enterobacteriaceae. PSI-2 appears to have been acquired
      horizontally as far back as the Erwinia/Pantoea common ancestor, with evidence of
      more recent horizontal acquisition of the PSI-3 system. Our results suggest that
      Pantoea is a relatively old plant pathogen that has lost and subsequently
      regained different plant-associated T3SSs. This work has broad implications for
      understanding the host-associating capacity of Pantoea strains, and reveals the
      propensity for Pantoea isolates to exchange pathogenicity determinants with human
      pathogenic members of the Enterobacteriaceae. 

PMID- 25982744
TI  - The ARF, AUX/IAA and GH3 gene families in citrus: genome-wide identification and
      expression analysis during fruitlet drop from abscission zone A.
AB  - Completion of the whole genome sequencing of citrus enabled us to perform genome
      wide identification and functional analysis of the gene families involved in
      agronomic traits and morphological diversity of citrus. In this study, 22 CitARF,
      11 CitGH3 and 26 CitAUX/IAA genes were identified in citrus, respectively.
      Phylogenetic analysis revealed that all the genes of each gene family could be
      subdivided into three groups and showed strong evolutionary conservation. The GH3
      and AUX/IAA gene families shrank and ARF gene family was highly conserved in the
      citrus genome after speciation from Arabidopsis thaliana. Tissue-specific
      expression profiles revealed that 54 genes were expressed in at least one tissue
      while just 5 genes including CitARF07, CitARF20, CitGH3.04, CitAUX/IAA25 and
      CitAUX/IAA26 with very low expression level in all tissues tested, suggesting
      that the CitARF, CitGH3 and CitAUX/IAA gene families played important roles in
      the development of citrus organs. In addition, our data found that the expression
      of 2 CitARF, 4 CitGH3 and 4 AUX/IAA genes was affected by IAA treatment, and 7
      genes including, CitGH3.04, CitGH3.07, CitAUX/IAA03, CitAUX/IAA04, CitAUX/IAA18,
      CitAUX/IAA19 and CitAUX/IAA23 were related to fruitlet abscission. This study
      provides a foundation for future studies on elucidating the precise role of
      citrus ARF, GH3 and AUX/IAA genes in early steps of auxin signal transduction and
      open up a new opportunity to uncover the molecular mechanism underlying citrus
      fruitlet abscission. 

PMID- 25982745
TI  - Hepatocyte fate upon TGF-beta challenge is determined by the matrix environment.
AB  - Primary hepatocytes are a versatile tool to investigate all aspects of liver
      function, and frequently used in drug development and testing. Upon TGF-beta
      challenge, hepatocytes either undergo an epithelial to mesenchymal transition
      (EMT) or apoptosis: culture on stiff collagen (monolayer) results in EMT whereas
      hepatocytes in a soft collagen matrix (sandwich) undergo programmed cell death.
      In this study, we analyzed the transcriptional programs triggered by TGF-beta
      under different culture conditions. Our results indicate that TGF-beta initiates
      an identical transcription profile in hepatocytes irrespective of the cellular
      environment. The fact that we nevertheless observe two vastly different
      phenotypes indicates that the matrix environment rather than the TGF-beta induced
      expression signature is the major determinant of the hepatocellular response. To
      confirm the impact of the surrounding matrix environment on the hepatocytes'
      phenotype in response to TGF-beta signaling, we studied the effect of Snail
      overexpression and knockout in both culture conditions. Neither genetic
      manipulation showed an impact on hepatocytes' fate upon TGF-beta treatment,
      confirming the crucial role of the surrounding matrix. Our findings provide novel
      insights into the hepatocellular basis of the fate decision between EMT and
      apoptotic cell death, and might explain why liver cells can react in very
      different manners to identical stimuli when tissue remodeling has changed the
      matrix environment, as occurs in a fibrotic liver. 

PMID- 25982746
TI  - Isolation of genes conferring salt tolerance from Piriformospora indica by random
      overexpression in Escherichia coli.
AB  - Piriformospora indica, a root endophytic fungus identified in the Indian Thar
      desert, colonizes the roots of plants and provides resistance towards biotic
      stress as well as tolerance to abiotic stress in the plants. Despite its positive
      impact on the host, little is known about the P. indica genes that are involved
      in salt stress tolerance. Therefore this study was conducted to identify and
      isolate high salinity-tolerance genes from P. indica. Thirty-six salinity
      tolerance genes were obtained by functional screening, based on random over
      expression of a P. indica cDNA library in Escherichia coli grown on medium
      supplemented with 0.6 M NaCl. The salinity tolerance conferred by these 36 genes
      in bacteria was further confirmed by using another strain of E. coli (DH5alpha)
      transformants. However when the expression of these 36 genes was analysed in P.
      indica using quantitative RT-PCR, we found only six genes were up-regulated by
      salt stress. These six genes are involved in different cellular processes, such
      as metabolism, energy and biosynthetic processes, DNA repair, regulation of
      protein turnover, transport and salt stress tolerance. This work presents the
      basis for further molecular analyses of the mechanisms of salt tolerance in P.
      indica and for the use of this endophyte to confer salt tolerance to plants.

PMID- 25982747
TI  - Chitinolytic Streptomyces vinaceusdrappus S5MW2 isolated from Chilika lake, India
      enhances plant growth and biocontrol efficacy through chitin supplementation
      against Rhizoctonia solani.
AB  - A chitinolytic actinomycete Streptomyces vinaceusdrappus S5MW2 was isolated from
      water sample of Chilika lake, India and identified using 16S rRNA gene
      sequencing. It showed in vitro antifungal activity against the sclerotia
      producing pathogen Rhizoctonia solani in a dual culture assay and by chitinase
      enzyme production in a chitin supplemented minimal broth. Moreover, isolate S5MW2
      was further characterized for biocontrol (BC) and plant growth promoting features
      in a greenhouse experiment with or without colloidal chitin (CC). Results of
      greenhouse experiment showed that CC supplementation with S5MW2 showed a
      significant growth of tomato plants and superior disease reduction as compared to
      untreated control and without CC treated plants. Moreover, higher accumulation of
      chitinase also recovered in the CC supplemented plants. Significant effect of CC
      also concurred with the Analysis of Variance of greenhouse parameters. These
      results show that the a marine antagonist S5MW2 has BC efficiency against R.
      solani and chitinase enzyme played important role in plant resistance. 

PMID- 25982748
TI  - Purification and partial characterization of a thermostable antimicrobial protein
      from Bacillus subtilis FB123.
AB  - Antimicrobial proteins/peptides have attracted much attention because of their
      potential use in the industrial setting. In the present study, a thermostable
      antimicrobial protein (BSAMP) was purified from the culture supernatant of
      Bacillus subtilis FB123 by ammonium sulfate precipitation, gel chromatography on
      Sephacryl S-200 High Resolution, and ion exchange chromatography on DEAE
      Sepharose Fast Flow column. The molecular weight of the purified BSAMP was 54
      kDa, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      both in the absence and presence of beta-mercaptoethanol. Its isoelectric point
      was determined to be 5.24 by isoelectric focusing electrophoresis. Periodic acid
      Schiff staining revealed BSAMP to be a glycoprotein. Maximum activity was
      obtained at pH 6.0, with over 79% maximum activity retained at pH 3.0-5.0 and pH
      7.0-9.0, respectively. BSAMP was shown to be highly thermostable, as its activity
      did not change obviously after treatment at 100  degrees C. However, it was
      partially sensitive to papain, trypsin, and alkali proteases. Finally, the
      bacterial protein exhibited broad-spectrum antimicrobial activity against several
      pathogenic organisms. These findings suggested that BSAMP should be further
      developed as a natural antibacterial agent for disease prevention in aquiculture
      and agriculture.

PMID- 25982750
TI  - Pain Assessment Strategies in Home Care and Nursing Homes in Mid-Norway: A Cross
      sectional Survey.
AB  - The prevalence of pain ranges from 27.8% to 86.5% in nursing homes and 42% to 50%
      in home care. Pain assessment is the first step toward effective pain management.
      The aim of this study was to explore the use of pain assessment strategies
      (verbal, numeric, and observation rating scales and standardized questions) in
      home care and nursing homes. The study was a descriptive cross-sectional survey.
      Health care providers who were responsible for the patients' medications replied
      to a questionnaire. In-home care and nursing homes in 11 randomly selected
      municipalities in Mid-Norway were included. Three hundred ninety-two individuals
      were included in this study (70% response rate): 271 (69%) from nursing homes and
      121 (31%) from home care. The respondents working in home care had a higher
      educational level than those in working in nursing homes. Pain assessment
      instruments were not used frequently in nursing homes and home care. Verbal and
      numeric rating scales were used significantly more frequently in home care than
      in nursing homes. Registered nurses (RNs) in nursing homes used standardized
      questions significantly more often than did RNs in home care. RNs and social
      educators in home care self-reported less competence in treating the patients'
      total pain experience than did those in nursing homes. Workplace (working in home
      care) and regular training in the use of pain assessment tools explained more
      than 20% of the variation in the use of pain assessment tools. Regular training
      in the use of pain assessment tools is needed for health care workers in home
      care and nursing homes. 

PMID- 25982751
TI  - Depth of anaesthesia monitoring during procedural sedation and analgesia: a
      systematic review protocol.
AB  - BACKGROUND: Procedural sedation and analgesia (PSA) is used to attenuate the pain
      and distress that may otherwise be experienced during diagnostic and
      interventional medical or dental procedures. As the risk of adverse events
      increases with the depth of sedation induced, frequent monitoring of level of
      consciousness is recommended. Level of consciousness is usually monitored during
      PSA with clinical observation. Processed electroencephalogram-based depth of
      anaesthesia (DoA) monitoring devices provide an alternative method to monitor
      level of consciousness that can be used in addition to clinical observation.
      However, there is uncertainty as to whether their routine use in PSA would be
      justified. Rigorous evaluation of the clinical benefits of DoA monitors during
      PSA, including comprehensive syntheses of the available evidence, is therefore
      required. One potential clinical benefit of using DoA monitoring during PSA is
      that the technology could improve patient safety by reducing sedation-related
      adverse events, such as death or permanent neurological disability. We
      hypothesise that earlier identification of lapses into deeper than intended
      levels of sedation using DoA monitoring leads to more effective titration of
      sedative and analgesic medications, and results in a reduction in the risk of
      adverse events caused by the consequences of over-sedation, such as hypoxaemia.
      The primary objective of this review is to determine whether using DoA monitoring
      during PSA in the hospital setting improves patient safety by reducing the risk
      of hypoxaemia (defined as an arterial partial pressure of oxygen below 60 mmHg or
      percentage of haemoglobin that is saturated with oxygen [SpO(2)] less than 90 %).
      Other potential clinical benefits of using DoA monitoring devices during sedation
      will be assessed as secondary outcomes. METHODS/DESIGN: Electronic databases will
      be systematically searched for randomized controlled trials comparing the use of
      depth of anaesthesia monitoring devices with clinical observation of level of
      consciousness during PSA. Language restrictions will not be imposed. Screening,
      study selection and data extraction will be performed by two independent
      reviewers. Disagreements will be resolved by discussion. Meta-analyses will be
      performed if suitable. DISCUSSION: This review will synthesise the evidence on an
      important potential clinical benefit of DoA monitoring during PSA within hospital
      settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017251.

PMID- 25982749
TI  - Aging-related anatomical and biochemical changes in lymphatic collectors impair
      lymph transport, fluid homeostasis, and pathogen clearance.
AB  - The role of lymphatic vessels is to transport fluid, soluble molecules, and
      immune cells to the draining lymph nodes. Here, we analyze how the aging process
      affects the functionality of the lymphatic collectors and the dynamics of lymph
      flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of
      matrix proteins, and smooth muscle cells in aged collectors resulting in a
      decrease in contraction frequency, systolic lymph flow velocity, and pumping
      activity, as measured in vivo in lymphatic collectors. Functionally, this
      impairment also translated into a reduced ability for in vivo bacterial transport
      as determined by time-lapse microscopy. Ultrastructural and proteomic analysis
      also indicates a decrease in the thickness of the endothelial cell glycocalyx and
      loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis
      mapped an aging-related increase in the glycation and carboxylation of
      lymphatic's endothelial cell and matrix proteins. Functionally, these
      modifications translate into apparent hyperpermeability of the lymphatics with
      pathogen escaping from the collectors into the surrounding tissue and a decreased
      ability to control tissue fluid homeostasis. Altogether, our data provide a
      mechanistic analysis of how the anatomical and biochemical changes, occurring in
      aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and
      pathogen transport. 

PMID- 25982752
TI  - Transition of serine residues to the D-form during the conversion of ovalbumin
      into heat stable S-ovalbumin.
AB  - Ovalbumin, a major protein in chicken egg white, is converted into a more
      thermostable molecular form, known as S-ovalbumin, during the storage of shell
      eggs. Our previous X-ray crystallographic study indicated that S-ovalbumin
      contains three D-Ser residues (S164, S236, and S320), which may account for its
      thermostability. Here, we confirmed the presence of these D-Ser residues in
      ovalbumin using a technique combining deuterium labeling of alpha-protons of
      amino acids and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Ovalbumin from chicken egg white and recombinant ovalbumin were incubated for
      approximately 12 days at pH 9.5 and 37 degrees C. They were then hydrolyzed in
      DCl/D2O vapor, derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F),
      and analyzed by LC-MS/MS. A time-dependent increase in the D-Ser contents in
      native ovalbumin was observed over a period of 7 days, reaching approximately 8%.
      This corresponds to a value of three serine residues per molecule, and is
      consistent with the prediction based on our previous crystallographic analysis.
      Nearly identical results were obtained with recombinant ovalbumin. We then used
      this technique to investigate whether D-amino acid residues could arise within
      other proteins under mild alkaline conditions and detected small but significant
      amounts of D-Ala and/or D-Ser residues that increased in a time-dependent manner
      in some proteins.

PMID- 25982753
TI  - Enantioselective analysis of D- and L-amino acids from mouse macrophages using
      high performance liquid chromatography.
AB  - The intrinsic D-amino acid profile of mouse macrophages extracted from the
      peritoneal cavity was analyzed using high performance liquid chromatography. Six
      D-amino acids (D-Asp, D-Ser, D-Ala, D-Leu, D-Gln and D-Lys) were detected in cell
      lysates of mouse macrophages. The content and the D/D+L ratio differed depending
      on the type of D-amino acid and were approximately 3.5-22 nmol/g cells, and
      approximately 1-20%, respectively. The D-amino acid composition of RAW 264.7
      cells, which is a model macrophage cell line, was similar to that of the mouse
      macrophage. These results suggest that macrophages and RAW 264.7 cells with
      macrophage-like functions have a similar D-amino acid profile.

PMID- 25982754
TI  - Allergic contact dermatitis caused by topical antiacne drugs.
AB  - Acne is a chronic inflammatory disease for which a long-lasting therapy, very
      often with topical drugs, is necessary. Despite the fact that several topical
      antiacne drugs (in particular, tretinoin, benzoyl peroxide, clindamycin and
      erythromycin) are used for many years, often on broad skin surfaces and for long
      periods of time, their potential for contact sensitization is low. Their
      potential for phototoxic and photoallergic reactions is also low. Much more
      frequent is irritant contact dermatitis caused by some of these drugs, in
      particular, retinoids and benzoyl peroxide, for which the short contact therapy
      has been recently suggested. 

PMID- 25982756
TI  - Assembly of Mesoporous Metal-Organic Framework Templated by an Ionic
      Liquid/Ethylene Glycol Interface.
AB  - We propose a facile room-temperature synthesis of a metal-organic framework (MOF)
      with a bimodal mesoporous structure (3.9 and 17-28 nm) in an ionic liquid
      (IL)/ethylene glycol (EG) mixture. The X-ray diffraction analysis reveals that
      MOF formation can be efficiently promoted by the presence of the EG/IL interface
      at room temperature. The MOFs with mesoporous networks are characterized by SEM
      and TEM. The formation mechanism of the mesoporous MOF in EG/IL mixture is
      investigated. It is proposed that the EG nanodroplets in the IL work as templates
      for the formation of the large mesopores. The as-synthesized mesoporous metal
      organic framework is an effective and reusable heterogeneous catalyst to catalyze
      the aerobic oxidation of benzylic alcohols. 

PMID- 25982755
TI  - Familial neonatal seizures in 36 families: Clinical and genetic features
      correlate with outcome.
AB  - OBJECTIVE: We evaluated seizure outcome in a large cohort of familial neonatal
      seizures (FNS), and examined phenotypic overlap with different molecular lesions.
      METHODS: Detailed clinical data were collected from 36 families comprising two or
      more individuals with neonatal seizures. The seizure course and occurrence of
      seizures later in life were analyzed. Families were screened for KCNQ2, KCNQ3,
      SCN2A, and PRRT2 mutations, and linkage studies were performed in mutation
      negative families to exclude known loci. RESULTS: Thirty-three families fulfilled
      clinical criteria for benign familial neonatal epilepsy (BFNE); 27 of these
      families had KCNQ2 mutations, one had a KCNQ3 mutation, and two had SCN2A
      mutations. Seizures persisting after age 6 months were reported in 31% of
      individuals with KCNQ2 mutations; later seizures were associated with frequent
      neonatal seizures. Linkage mapping in two mutation-negative BFNE families
      excluded linkage to KCNQ2, KCNQ3, and SCN2A, but linkage to KCNQ2 could not be
      excluded in the third mutation-negative BFNE family. The three remaining families
      did not fulfill criteria of BFNE due to developmental delay or intellectual
      disability; a molecular lesion was identified in two; the other family remains
      unsolved. SIGNIFICANCE: Most families in our cohort of familial neonatal seizures
      fulfill criteria for BFNE; the molecular cause was identified in 91%. Most had
      KCNQ2 mutations, but two families had SCN2A mutations, which are normally
      associated with a mixed picture of neonatal and infantile onset seizures.
      Seizures later in life are more common in BFNE than previously reported and are
      associated with a greater number of seizures in the neonatal period. Linkage
      studies in two families excluded known loci, suggesting a further gene is
      involved in BFNE.

PMID- 25982762
TI  - Peer reviewers: "What are they thinking?".

PMID- 25982757
TI  - Does a diet low in FODMAPs reduce symptoms associated with functional
      gastrointestinal disorders? A comprehensive systematic review and meta-analysis.
AB  - BACKGROUND: Functional gastrointestinal symptoms such as abdominal pain,
      bloating, distension, constipation, diarrhea and flatulence have been noted in
      patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).
      The diversity of symptoms has meant that finding an effective treatment has been
      challenging with most treatments alleviating only the primary symptom. A novel
      treatment option for IBS and IBD currently generating much excitement is the low
      fermentable, oligo-, di-, mono-saccharides and polyol (FODMAP) diet. The aim of
      this meta-analysis was to determine the evidence of the efficacy of such a diet
      in the treatment of functional gastrointestinal symptoms. METHODS: Electronic
      databases were searched through to March 2015 to identify relevant studies.
      Pooled odds ratios (ORs) and 95 % confidence intervals were calculated for the
      effect of a low FODMAP diet on the reduction in IBS [Symptoms Severity Score
      (SSS)] score and increase in IBS quality of life (QOL) score for both randomized
      clinical trials (RCTs) and non-randomized interventions using a random-effects
      model. RESULTS: Six RCTs and 16 non-randomized interventions were included in the
      analysis. There was a significant decrease in IBS SSS scores for those
      individuals on a low FODMAP diet in both the RCTs (OR 0.44, 95 % CI 0.25-0.76; I
      (2) = 35.52, p = 0.00) and non-randomized interventions (OR 0.03, 95 % CI 0.01
      0.2; I (2) = 69.1, p = 0.02). In addition, there was a significant improvement in
      the IBS-QOL score for RCTs (OR 1.84, 95 % CI 1.12-3.03; I (2) = 0.00, p = 0.39)
      and for non-randomized interventions (OR 3.18, 95 % CI 1.60-6.31; I (2) = 0.00, p
      = 0.89). Further, following a low FODMAP diet was found to significantly reduce
      symptom severity for abdominal pain (OR 1.81, 95 % CI 1.13-2.88; I (2) = 0.00, p
      = 0.56), bloating (OR 1.75, 95 % CI 1.07-2.87; I (2) = 0.00, p = 0.45) and
      overall symptoms (OR 1.81, 95 % CI 1.11-2.95; I (2) = 0.00, p = 0.4) in the RCTs.
      In the non-randomized interventions similar findings were observed. CONCLUSION:
      The present meta-analysis supports the efficacy of a low FODMAP diet in the
      treatment of functional gastrointestinal symptoms. Further research should ensure
      studies include dietary adherence, and more studies looking at greater number of
      patients and long-term adherence to a low FODMAP diet need to be conducted.

PMID- 25982763
TI  - Getting what we pay for.

PMID- 25982764
TI  - Internationally recruited nurses' experiences in England: A survey approach.
AB  - BACKGROUND: Over the past few years, there has been an impetus to recruit
      internationally registered nurses to work in the National Health Service (NHS) to
      avert the labor shortage inherent in the United Kingdom. PURPOSE: To determine
      internationally registered nurses' perception of discrimination, support, and
      their adjustment to a new environment in the NHS in England. METHODS: A
      descriptive survey was used. Data were collected from 188 internationally
      recruited nurses using a questionnaire approach from 15 National Health Service
      hospitals in England. Data were analyzed using chi-square, Fisher exact, or
      Kruskal-Wallis tests. RESULTS: The study had a 21% response rate. There were
      81.9% females and 18.1% males who participated in the survey. A mean score of
      7.55 and standard deviation of 6.82 were calculated for the number of years of
      experience of working in the NHS. The findings revealed many statistical
      differences between the different ethnic groups used in the study. Generally,
      internationally recruited nurses from Africa, in particular, perceived
      discrimination to be evident in the workplace, the support they received was
      limited, and their adjustment to a new environment was the weakest in comparison
      with the other internationally recruited nurses from the different data sets.
      CONCLUSION: Although the needs of all internationally recruited nurses should be
      considered, it would appear that the needs of African nurses are the greatest
      because the study found that they experienced challenges in the working
      environment in the NHS.

PMID- 25982765
TI  - An eHealth education intervention to promote healthy lifestyles among nurses.
AB  - BACKGROUND: Nurses often do not adhere to health-promoting lifestyles,
      compromising their health status and quality of care. This study aimed to
      evaluate health-promoting effects of an eHealth intervention among nurses
      compared with conventional handbook learning. METHODS: This controlled
      before/after study enrolled 105 nurses, 55 in an experimental group and 60 in a
      control group, for 3 months of intervention. Both groups completed pre- and
      postintervention questionnaires of the Health-Promoting Lifestyle Profile and
      Short-Form Health Survey. Subjects' height, weight, and body mass index were
      recorded. DISCUSSION: The eHealth education intervention had the effect of
      significantly increasing nurses' postintervention Health-Promoting Lifestyle
      Profile total scores. No significant changes were observed in the
      postintervention scores of the control group subjects. The experimental group
      also had significant postintervention decreases in BMI, but no similar changes
      were observed in the control group. CONCLUSIONS: Tailored eHealth education is an
      effective and accessible intervention for enhancing health-promoting behavior
      among nurses.

PMID- 25982766
TI  - Essential elements of the relationship between the nurse and the person with
      advanced and terminal cancer: A meta-ethnography.
AB  - OBJECTIVE: The purpose of this study was to understand how the nurse-patient
      relationship is interpreted by nurses and patients with advanced and terminal
      cancer (ATC) and which aspects of this relationship are perceived to be the most
      valuable for patients. METHODS: A literature search was conducted using the
      Cumulative Index to Nursing and Allied Health (CINAHL), PubMed, and PsycINFO
      databases and was supported by reviewing reference lists. Nine articles were
      selected, and the quality of them was assessed using the Critical Appraisal
      Skills Program. A synthesis was performed following the seven-stage meta
      ethnography described by Noblit and Hare. RESULTS: Four primary themes were
      derived from the synthesis: (a) being with and being for the person with ATC, (b)
      time is required for establishing the relationship, (c) the influence of the
      primary actors in the relationship: the nurse and the person with ATC, and (d)
      the effects of the relationship on both the nurse and the person with ATC.
      Finally, an explanatory model of the relationship between the nurse and the
      patient with ATC was developed, which shows that the relationship is an
      interpersonal process with several key elements including familiarity with one
      another, reciprocity, respect, and confidence. The nurses and patients with ATC
      perceive that their relationship is important and beneficial. The patients demand
      a helping and caring relationship focused on them as persons, not only as
      patients. CONCLUSIONS: Patients with ATC and nurses consider their relationship
      to be important and beneficial. An approach to caring focused on patients as
      persons should be fostered among health care professionals and students.

PMID- 25982767
TI  - Professional autonomy and work setting as contributing factors to depression and
      absenteeism in Canadian nurses.
AB  - OBJECTIVES: The prevalence of major depression in Canadian nurses is double the
      national average for working women. The present study sought to delineate the
      role of professional autonomy, health care setting, and work environment
      characteristics as risk factors for depression and absenteeism in female nurses.
      METHODS: A cross-sectional, secondary analysis was conducted on a large
      representative sample of female nurses working in hospitals and other settings
      across Canada (N = 17,437). Univariate and multivariate analyses were used to
      test the hypothesis that work environment factors are significant determinants of
      major depression and absenteeism in female nurses after accounting for other risk
      factors. RESULTS: Experiencing a major depressive episode in the past 12 months
      was significantly associated with lower autonomy (odds ratio [OR] = 0.93), higher
      job strain (OR = 2.2), being a licensed practical nurse (OR = 0.82), and working
      in a nonhospital setting (OR = 1.5). Higher absenteeism was associated with the
      same variables as well as having less control over one's work schedule.
      CONCLUSIONS: Efforts to increase autonomy of nurses and reduce job strain may
      help to address the high prevalence of major depression in this professional
      group.

PMID- 25982768
TI  - Electronic personal health record use among registered nurses.
AB  - INTRODUCTION: Nurses promote self-care and active participation of individuals in
      managing their health care, yet little is known about their own use of electronic
      personal health records (ePHRs). The purpose of this study was to examine factors
      associated with ePHR use by nurses for their own health management. METHODS: A
      total of 664 registered nurses working in 12 hospitals in the Maryland and
      Washington DC area participated in an online survey from December 2013 to January
      2014. Multiple logistic regression models identified factors associated with ePHR
      use. RESULTS: More than a third (41%; 95% confidence interval [CI], 0.37-0.44) of
      the respondents were ePHR users. There was no variation between ePHR users and
      nonusers by demographic or job-related information. However, ePHR users were more
      likely to be active health care consumers (i.e., have a chronic medical condition
      and take prescribed medications; odds ratio [OR] = 1.64; 95% CI, 1.06-2.53) and
      have health care providers who used electronic health records for care (OR =
      3.62; 95% CI, 2.45-5.36). CONCLUSIONS: Nurses were proactive in managing their
      chronic medical conditions and prescribed medication use with ePHRs. ePHR use by
      nurses can be facilitated by increasing use of electronic health records.

PMID- 25982769
TI  - A proposed conceptual model of nursing and population health.
AB  - OBJECTIVE: To describe a Conceptual Model of Nursing and Population Health about
      the intersection of nursing and population health. METHODS: Review of literature
      and derivation of a new conceptual model. RESULTS: The conceptual model concepts
      are upstream factors, population factors, health care system factors, nursing
      activities, and population health outcomes. Nursing activities mediate the
      indirect relations of upstream, population, and health care system factors with
      population health outcomes; in addition, health care system factors and nursing
      activities are directly related to population health outcomes. Implications for
      research methods, revisions in all levels of nursing education, and population
      focused advances in nursing practice are identified. CONCLUSION: The strength of
      the model is its emphasis on attainment of the highest possible quality of life
      for populations, by means of nursing activities directed to promote or restore
      and maintain wellness across the life course and to prevent disease.

PMID- 25982771
TI  - Validity and model-based reliability of the Work Organisation Assessment
      Questionnaire among nurses.
AB  - BACKGROUND: The Work Organisation Assessment Questionnaire (WOAQ) was developed
      as part of a risk assessment tool for the manufacturing setting (Griffiths, Cox,
      Karanika, Khan, Tomas, 2006). The WOAQ was used in this study to assess its
      validity and model-based reliability among Australian nurses using a conventional
      second-order and a bifactor confirmatory factor analysis (CFA). METHODS: This
      article reports a study of Australian participants (N = 312) to validate a
      multidimensional measure of the WOAQ. Data were collected from a group of
      Australian community nurses. CFA was performed comparing a conventional second
      order model and a bifactor model of one WOAQ summative factor and its five
      subfactors, which together described the most common issues of work design and
      management in organizations. A group of close fit indices that include relatively
      greater penalties for model complexity (i.e., the root mean square error of
      approximation, Non-normed Fit Index, and the Akaike Information Criterion) were
      chosen to interpret the results. RESULTS: The results of reliability and validity
      analysis revealed some evidence for the summative measure of the WOAQ. Results
      indicate that the questionnaire is a valid and reliable scale, but some
      subfactors are more plausible than others within the Australian nursing
      community. CONCLUSION: The study provides future researchers some guidance for
      bifactor modeling in organizational studies of this type. The WOAQ provides
      flexibility to measure risk assessment and management procedures.

PMID- 25982772
TI  - Conceptualizing surrogate decision making at end of life in the intensive care
      unit using cognitive task analysis.
AB  - BACKGROUND: Surrogate decision makers (SDMs) face difficult decisions at end of
      life (EOL) for decisionally incapacitated intensive care unit (ICU) patients.
      PURPOSE: To identify and describe the underlying psychological processes of
      surrogate decision making for adults at EOL in the ICU. METHODS: Qualitative case
      study design using a cognitive task analysis interviewing approach. Participants
      were recruited from October 2012 to June 2013 from an academic tertiary medical
      center's ICU located in the rural Northeastern United States. Nineteen SDMs for
      patients who had died in the ICU completed in-depth semistructured cognitive task
      analysis interviews. DISCUSSION: The conceptual framework formulated from data
      analysis reveals that three underlying, iterative, psychological dimensions (gist
      impressions, distressing emotions, and moral intuitions) impact an SDM's judgment
      about the acceptability of either the patient's medical treatments or his or her
      condition. CONCLUSION: The framework offers initial insights about the underlying
      psychological processes of surrogate decision making and may facilitate enhanced
      decision support for SDMs.

PMID- 25982773
TI  - Human papillomavirus vaccination uptake and completion as a preventive health
      measure among female adolescents.
AB  - BACKGROUND: National coverage for the human papillomavirus (HPV) vaccine falls
      short of the targeted goals for Healthy People 2020 with disparities in
      completion rates noted in minority adolescent female populations. The purpose of
      this study was to provide a review of the literature on HPV vaccination uptake
      and completion rates among female minority adolescents as well as a discussion of
      the financial and policy dimensions of HPV vaccination with implications that
      impact uptake and completion rates. METHODS: By reviewing the literature, the
      authors show that the two human papillomavirus (HPV) vaccines, Gardasil and
      Cervarix, have presented unprecedented opportunities to prevent morbidity and
      mortality from cervical cancer. CONCLUSION: The authors recommend that nurses and
      advanced practice nurses take an active role at the point of care to educate
      families about HPV vaccination. Nursing interventions for practice changes are
      provided to improve vaccination initiation and completion rates in disadvantaged
      populations.

PMID- 25982775
TI  - Free energy pathways of a multistable liquid crystal device.
AB  - The planar bistable device [Tsakonas et al., Appl. Phys. Lett., 2007, 90, 111913]
      is known to have two distinct classes of stable equilibria: the diagonal and
      rotated solutions. We model this device within the two-dimensional Landau-de
      Gennes theory, with a surface potential and without any external fields. We
      systematically compute a special class of transition pathways, referred to as
      minimum energy pathways, between the stable equilibria that provide new
      information about how the equilibria are connected in the Landau-de Gennes free
      energy landscape. These transition pathways exhibit an intermediate transition
      state, which is a saddle point of the Landau-de Gennes free energy. We
      numerically compute the structural details of the transition states, the optimal
      transition pathways and the free energy barriers between the equilibria, as a
      function of the surface anchoring strength. For strong anchoring, the transition
      pathways are mediated by defects whereas we get defect-free transition pathways
      for moderate and weak anchoring. In the weak anchoring limit, we recover a cusp
      catastrophe situation for which the rotated state acts as a transition state
      connecting two different diagonal states. 

PMID- 25982770
TI  - Social networks and future direction for obesity research: A scoping review.
AB  - Despite significant efforts to decrease obesity rates, the prevalence of obesity
      continues to increase in the United States. Obesity risk behaviors including
      physical inactivity, unhealthy eating, and sleep deprivation are intertwined
      during daily life and are difficult to improve in the current social environment.
      Studies show that social networks-the thick webs of social relations and
      interactions-influence various health outcomes, such as HIV risk behaviors,
      alcohol consumption, smoking, depression, and cardiovascular mortality; however,
      there is limited information on the influences of social networks on obesity and
      obesity risk behaviors. Given the complexities of the biobehavioral pathology of
      obesity and the lack of clear evidence of effectiveness and sustainability of
      existing interventions that are usually focused on an individual approach,
      targeting change in an individual's health behaviors or attitude may not take
      sociocontextual factors into account; there is a pressing need for a new
      perspective on this problem. In this review, we evaluate the literature on social
      networks as a potential approach for obesity prevention and treatment (i.e., how
      social networks affect various health outcomes), present two major social network
      data analyses (i.e., egocentric and sociometric analysis), and discuss
      implications and the future direction for obesity research using social networks.

PMID- 25982774
TI  - Brief motivational intervention for heavy drinking mandated and voluntary
      freshmen: A 1-year follow-up assessment.
AB  - BACKGROUND: Alcohol abuse among freshmen university students is a major public
      health issue with associated costs to individuals and the society of substantial
      morbidity, high-risk negative behaviors (e.g., blackouts, rape, suicide, and
      violence), and mortality. This longitudinal study compared the effectiveness of a
      brief motivational intervention (MI) in decreasing alcohol consumption and
      related consequences among mandated students and voluntary students. Readiness to
      change drinking behaviors was compared between the groups. METHODS: Eligible
      participants (710 voluntary and 190 mandated, N = 900) received MI at baseline
      and again at 2 weeks with boosters at 3, 6, and 12 months. Repeated-measures
      analysis of variance was used to compare the two groups. RESULTS: Alcohol use and
      related consequences in both groups decreased significantly between baseline and
      12 months. At baseline, a significantly larger percent of students from the
      mandated group than the voluntary group were in the action stage of change (52.1%
      vs. 27.5%), and a significantly smaller percentage of mandated students were in
      the precontemplation stage (p < .0001). DISCUSSION: MI effects were sustained
      over 12 months. Alcohol consumption and related consequences decreased
      significantly among the freshmen who were mandated to attend the program as well
      as among students who volunteered to participate in the study. The findings
      support the importance of advanced practice nurses conducting MI as an
      intervention with college students.

PMID- 25982776
TI  - In-vivo three-dimensional knee kinematics during daily activities in dogs.
AB  - The canine knee is morphologically similar to the human knee and thus dogs have
      been used in experimental models to study human knee pathology. To date, there is
      limited data of normal canine 3D knee kinematics during daily activities. The
      objective of this study was to characterize 3D in-vivo femorotibial kinematics in
      normal dogs during commonly performed daily activities. Using single-plane
      fluoroscopy, six normal dogs were imaged performing walk, trot, sit, and stair
      ascent activities. CT-generated bone models were used for kinematic measurement
      using a 3D-to-2D model registration technique. Increasing knee flexion angle was
      typically associated with increasing tibial internal rotation, abduction and
      anterior translation during all four activities. The precise relationship between
      flexion angle and these movements varied both within and between activities.
      Significant differences in axial rotation and coronal angulation were found at
      the same flexion angle during different phases of the walk and trot. This was
      also found with anterior tibial translation during the trot only. Normal canine
      knees accommodate motion in all planes; precise kinematics within this envelope
      of motion are activity dependent. This data establishes the characteristics of
      normal 3D femorotibial joint kinematics in dogs that can be used as a comparison
      for future studies.

PMID- 25982777
TI  - Rare case of iliopsoas hernia: incidental finding at laparoscopic total
      extraperitoneal hernia repair.

PMID- 25982779
TI  - IgM interference in the Abbott iVanco immunoassay: A case report.

PMID- 25982778
TI  - Development and validation of a method using supported liquid extraction for
      aldosterone determination in human plasma by LC-MS/MS.
AB  - BACKGROUND: Accurate quantitation of aldosterone is essential for screening,
      diagnosis and subtype classification in primary aldosteronism. A simple,
      sensitive method for aldosterone in human plasma using supported liquid
      extraction (SLE) in combination with liquid chromatography tandem mass
      spectrometry (LC-MS/MS) was developed and validated. METHODS: Plasma samples were
      diluted with water containing d7-aldosterone as internal standard. The samples
      were extracted with methyl-tert-butyl-ether (MTBE) on SLE cartridges. Separation
      was carried out on a Luna C18 (2) column using a methanol-water gradient.
      Detection was performed in the negative electrospray multiple reaction monitoring
      (MRM) quantitation. The use of water-based calibrators was evaluated against
      calibrators prepared in steroid-free serum. RESULTS: The assay was linear up to
      3265pmol/L with an LOQ of approximately 40pmol/L. Within-run and between-run
      precision for plasma aldosterone were less than 10% except at low level near LOQ
      but were still less than 14.7% (Westgard's desirable specification). The mean
      recovery of the analyte added to plasma was greater than 97.7% and matrix effects
      were less than 4%. Comparison with another LC-MS/MS method was performed on a
      more sensitive instrument (ABSciex TQ 5500) and gave the equation API
      3000=0.957*TQ 5500+12.6, linear regression r(2)=0.974 (n=43). An estimation of
      the reference interval for adults was established on a group of healthy
      volunteers (n=53). Calibration with water-based calibrators was validated and can
      be used for measurement of aldosterone by LC-MS/MS. CONCLUSIONS: This method is
      reliable, easy to perform on plasma specimens in a clinical environment and is
      attractive because of its simplicity.

PMID- 25982780
TI  - Targeted next-generation sequencing identifies novel compound heterozygous
      mutations of DYNC2H1 in a fetus with short rib-polydactyly syndrome, type III.
AB  - A 26-year-old woman with a past history of fetal skeletal dysplasia was referred
      to our institution at 24weeks of gestation following a routine sonographic
      diagnosis of short limbs in the fetus. A fetal ultrasound showed short limbs, a
      narrow thorax, short ribs with marginal spurs, and polydactyly. Conventional
      cytogenetics analysis of cultured amniocytes demonstrated that the fetal
      karyotype was normal. Using targeted exome sequencing of 226 known genes
      implicated in inherited skeletal dysplasia, we identified compound heterozygous
      mutations in the DYNC2H1 gene in the fetus with short rib-polydactyly syndrome,
      type III (SRPS III), c.1151 C>T(p.Ala384Val) and c.4351 C>T (p.Gln1451*), which
      were inherited from paternally and maternally, respectively. These variants were
      further confirmed using Sanger sequencing and have not been previously reported.
      To our knowledge, this is the first report of DYNC2H1 mutations causing SRPS III,
      in the Chinese population. Our findings expand the number of reported cases of
      this rare disease, and indicate that targeted next-generation sequencing (NGS) is
      an accurate, rapid, and cost-effective method in the genetic diagnosis of fetal
      skeletal dysplasia. 

PMID- 25982781
TI  - Is the imbalance between pro-angiogenic and anti-angiogenic factors associated
      with preeclampsia?
AB  - BACKGROUND: Preeclampsia (PE) is a multisystem disease characterized by the
      development of hypertension and proteinuria. Although PE etiology is not fully
      known, the placenta seems to play a central role in the development of disease.
      The inadequate placentation process results in a change in angiogenic factors
      levels, such as vascular endothelial growth factor (VEGF), placental growth
      factor (PlGF), soluble form of endoglin (s-Eng) and soluble form of vascular
      endothelial growth factor receptor type 1 (sFlt-1). OBJECTIVE: The aim of this
      review was to clarify if the imbalance between pro-angiogenic and anti-angiogenic
      factors is associated with PE. CONCLUSION: It is known that inadequate
      placentation process is the primary mechanism suggested for PE occurrence and
      angiogenic factors are involved in this process. The state-of-the-art suggests
      that progress in grasp the imbalance of pro-angiogenic and anti-angiogenic
      factors is essential for the improvement of knowledge about PE. The development
      of prospective, longitudinal studies with serial determinations of these factors
      throughout pregnancy is needed to better assess the relevance of these markers
      for understanding the etiology, prevention, diagnosis, prognosis and treatment of
      this challenging disease.

PMID- 25982782
TI  - [Report of the French "conference nationale de l'echographie obstetricale et
      foetale" (CNEOF)-- recommendations for focused prenatal ultrasound].
AB  - The conference has among its functions, to promote a quality assurance policy for
      obstetrics and foetal ultrasound scans by participating in the development of an
      information strategy for the professionals and the public on the interest and
      limits of these techniques, and in the development of rules for good practice.
      Thus, the conference produced in 2005 a good practice's recommendations report
      concerning the screening of ultrasound scans, with an actualised version in 2015,
      and has published in 2014 a similar report concerning second line prenatal
      ultrasound. The conference complements these recommendations by characterizing
      the third type of ultrasound scan, the "focused ultrasound scan", which is a
      daily tool for every practitioner in obstetrics. 

PMID- 25982783
TI  - Multiple cutaneous squamous cell carcinoma in cutaneous sarcoidosis.

PMID- 25982784
TI  - HTLV-1 viral RNA is detected rarely in plasma of HTLV-1 infected subjects.
AB  - Plasma of patients infected with HTLV-1 is considered non-infectious but
      detection of HTLV-1 genomic RNA in plasma has been recently reported. The aim of
      this project was to detect and quantify HTLV-1 RNA in plasma and assess its
      potential value in diagnosis and prognosis. RNA from 1 ml of plasma from 65
      subjects infected with HTLV-1 (27 asymptomatic carriers [AC]), 17 patients with
      HTLV-1-associated myelopathy (HAM/TSP), 14 with adult T-cell leukemia/lymphoma
      (ATLL), two co-infected with HIV, and five with other HTLV-1-associated disease,
      was extracted and reverse transcribed. HTLV-1 specific nested PCR was performed
      using primers to amplify the conserved Tax region. All samples were run in
      quadruplicate, nested PCR products were detected by gel electrophoresis. HTLV-1
      RNA was detected in plasma from 18 (28%) patients, always at a very low copy
      number (3-13 copies viral cDNA per milliliter of plasma). Mean values of HTLV-1
      proviral load did not differ between patients in whom HTLV-1 RNA was detected and
      patients in whom it was not possible to detect HTLV-1 RNA in plasma. HTLV-1
      genomic RNA can be detected in the plasma of a minority of patients but not at a
      level or frequency to be useful clinically or diagnostically. Lack of
      transmission of HTLV-1 by plasma is due to the rare presence of HTLV-1 virions,
      regardless of any other factor.

PMID- 25982785
TI  - Intravesical migration of a Chinese intrauterine device and secondary stone
      formation: diagnostic investigation and laparoscopic management.

PMID- 25982786
TI  - Ultrasonographic evaluation of urethrovesical junction mobility: correlation with
      type of delivery and stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: A relationship between urinary incontinence and
      hypermobility of the urethrovesical junction (UVJ) during pregnancy has been
      described. The aim of the study was to compare the effects of vaginal delivery
      (VD) and caesarean section (CS) on UVJ mobility. METHODS: The retrovesical angle
      (RVA) and the anterior angle between the UVJ and the pubic bone, the pubovesical
      angle (PVA), were evaluated ultrasonographically in controls and pregnant women
      during their first pregnancy between 38 and 40 weeks, and then re-evaluated 6
      weeks and 6 months after delivery. All patients completed a validated
      questionnaire (ICIQ-SF). Differences between and within groups were assessed with
      Student's t test, the chi-squared test for trend, and one-way two-tailed analysis
      of variance with Scheffe's post-hoc test. The correlation between PVA and RVA was
      evaluated using the Spearman R correlation. The positive predictive value,
      negative predictive value, sensitivity and specificity for the prediction of
      stress urinary incontinence (SUI) symptoms were also determined. RESULTS:
      Included in the study were 42 controls and 217 pregnant women. PVA at rest,
      during cough and Valsalva manoeuvre was significantly higher in pregnant women
      than in controls and in women 6 weeks after VD in comparison with women who had
      undergone CS. Patients affected by SUI showed a significantly higher PVA. RVA did
      not differ between subjects affected or not by SUI symptoms. PVA and RVA were not
      correlated with each other. CONCLUSIONS: PVA and RVA are increased in pregnant
      women in comparison with controls. In patients undergoing VD, PVA is restored
      significantly later than in those undergoing CS. The change in RVA after
      pregnancy and delivery seems to persist longer than the change in PVA.

PMID- 25982787
TI  - Successful use of ring pessary with support for advanced pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Support pessaries are not recommended for patients
      with advanced prolapse. This study aimed to explore the efficacy of the ring
      pessary with support for the treatment of advanced pelvic organ prolapse (POP).
      METHODS: We conducted this prospective study on pessary fittings performed
      between November 2013 and September 2014 at the Department of Obstetrics and
      Gynecology, Peking Union Medical College Hospital (PUMCH), Beijing. A total of
      109 patients with stage III or IV POP completed a detailed history. A successful
      fitting was defined as the continued use of the device for over 3 months from the
      initial fitting. Data were analyzed with the Wilcoxon rank-sum test, independent
      sample t tests, continuity correction chi(2) tests, and Fisher's exact test.
      RESULTS: A total of 74.3 % (81/109) of the patients were successfully fitted with
      the ring pessary with support at the initial visit. Among those women with a
      successful initial fitting, the failure rate was less than 10 % (8/81) at 3
      months. Furthermore, 82.7 % (67/81) of the patients were able to manage the
      pessary by themselves. Seven patients experienced vaginal erosion. There was no
      association of prolapse stage and the predominant prolapse compartment with
      pessary trial outcome. The average vaginal length of the patients with successful
      pessary use was 7.58 cm. CONCLUSIONS: The ring pessary with support was
      successfully fitted in patients with advanced POP with a high success rate and
      few complications. Older patients were more likely to prefer the ring pessary
      with support due to its convenient use.

PMID- 25982788
TI  - Intake ratio of 131I to 137Cs derived from thyroid and whole-body doses to
      Fukushima residents.
AB  - This study deals with the intake ratio of (131)I to (137)Cs that allows for the
      utilisation of late whole-body measurements to reconstruct the internal thyroid
      doses to Fukushima residents. The ratio was derived from the thyroid dose
      distribution of children and the effective dose distribution of adults based on
      the assumption that various age groups of persons inhaled the two nuclides at the
      same activity ratio and at around the same time, while taking into account age
      dependent ventilation rates. The two dose distributions were obtained from
      residents of Iitate village and Kawamata town, located northwest of Fukushima
      Daiichi nuclear power plant (FDNPP). As a result, the intake ratios for the
      residents were 2-3, which was much smaller than the activity ratio observed in
      air sampling. A main reason for this discrepancy presumably lies in the
      relatively smaller thyroid uptake for iodine in the Japanese subjects than that
      in the reference persons on whom the biokinetic model promulgated by
      International Commission on Radiological Protection is based. The actual intake
      ratio of the two nuclides is believed to have been higher south of the FDNPP;
      however, this would depend on which of three significant plume events dominantly
      contributed to the intake for individuals. Further studies are needed to clarify
      this issue as a part of the reconstruction of early internal doses related to the
      FDNPP accident. 

PMID- 25982789
TI  - Facing increasing challenges.

PMID- 25982790
TI  - Collaboration of local government and experts responding to increase in
      environmental radiation level due to the nuclear disaster: focusing on their
      activities and latest radiological discussion.
AB  - Activities were introduced in Kashiwa city in the Tokyo metropolitan area to
      correspond to the elevated environmental radiation level after the disaster of
      the Fukushima Daiichi nuclear power plant. These were based on a strong
      cooperation between local governments and experts. Ambient dose rate and
      radioactivity of foodstuff produced inside of the city have been monitored.
      Representative ambient dose rates around living environments have almost already
      become their original levels of the pre-accident because of the decontamination
      activity, natural washout and effective half-lives of radioactivity. The internal
      annual dose due to radioactive cesium under the policy of 'Local Production for
      Local Consumption' is estimated as extremely low comparing the variation range
      due to natural radioactivity. Systematic survey around a retention basin has been
      started. All of these latest monitoring data would be one of the core information
      for the policy making as well as a cost-benefit discussion and risk
      communication.

PMID- 25982791
TI  - The global economic crisis, household income and pre-adolescent overweight and
      underweight: a nationwide birth cohort study in Japan.
AB  - BACKGROUND: We hypothesized that children from lower income households and in
      households experiencing a negative income change in connection to the global
      economic crisis in 2008 would be at increased risk of adverse weight status
      during the subsequent years of economic downturn. METHODS: Data were obtained
      from a nationwide longitudinal survey comprising all children born during 2 weeks
      of 2001. For 16,403 boys and 15,206 girls, information about anthropometric
      measurements and household characteristics was collected from 2001 to 2011 on
      multiple occasions. Interactions between the crisis onset (September 2008) and
      household income group, as well as the crisis onset and a >30% negative income
      change in connection to the crisis, were assessed with respect to risk of
      childhood over- and underweight. RESULTS: Adjusted for household and parental
      characteristics, boys and girls in the lower household income quartiles had a
      larger increase in risk of overweight after the crisis onset relative to their
      peers in the highest income group. (Odds ratio (95% confidence interval) for
      interaction term in boys=1.23 (1.02-1.24); girls=1.35 (1.23-1.49) comparing the
      lowest with the highest income group.) Among girls, an interaction between the
      crisis onset and a >30% negative change in household income with respect to risk
      of overweight was observed (odds ratio for interaction term=1.23 (1.09-1.38)).
      Girls from the highest income group had an increased risk of underweight after
      the crisis onset compared with girls from the lowest income group. CONCLUSIONS:
      Boys and girls from lower household income groups and girls from households
      experiencing a negative income change in connection to the global economic crisis
      in 2008, may be at increased risk of overweight. Vulnerability to economic
      uncertainty could increase risk of overweight in preadolescence.

PMID- 25982792
TI  - Examination of whether early weight loss predicts 1-year weight loss among those
      enrolled in an Internet-based weight loss program.
AB  - One-month weight loss (WL) predicts posttreatment WL in face-to-face
      interventions; however, whether this holds true within Internet programs is
      unknown. This study examined whether 4-week WL predicts WL following a 12-week
      Internet program and at 6 and 12 months follow-up. A total of 181 participants
      (body mass index=33.4+/-5.5 kg m(-)(2); 83.1% female) received a 12-week behavior
      based Internet WL program consisting of weekly video lessons. Participants were
      given a daily WL, calorie and physical-activity goal and asked to enter these
      data on the study website weekly. Personalized feedback was provided. Using 4
      week WL, individuals were categorized as 'early nonresponders' (<2.0% WL) or
      'early responders' (?2.0% WL). Early nonresponders had significantly lower WL
      than early responders at 3 (-1.3+/-3.8% vs -6.3+/-4.3%), 6 (-1.7+/-5.1% vs -5.8+/
      5.2%) and 12 months (-0.05+/-6.8% vs -2.7+/-6.3%, P<0.05). The odds of achieving
      a ?5% WL were 8.5 (95% confidence interval (CI), 3.3-22.1), 3.4 (95% CI, 1.4-8.3)
      and 2.6 (95% CI, 0.93-7.4) times lower in early nonresponders, compared with
      early responders at 3, 6 and 12 months, respectively. Compared with early
      responders, early nonresponders viewed fewer video lessons and self-monitored
      less often across the 12-week intervention (P<0.05). This study provides initial
      evidence that a 4-week WL of <2.0% places an individual at an increased risk of
      failing to achieve clinically significant WL following an Internet program. 

PMID- 25982794
TI  - Cinobufagin exerts anti-proliferative and pro-apoptotic effects through the
      modulation ROS-mediated MAPKs signaling pathway.
AB  - Cinobufagin (CBG) is a cardiotoxic bufanolide steroid secreted by the skin and
      parotid venom glands of the Asiatic toad Bufo bufo gargarizans (called Chan-Su).
      Although CBG is known to exhibit anti-cancer activities, very little is known
      about its potential mechanism(s) of action. In this study, we investigated
      whether CBG mediates its effect through the modulation of the mitogen-activated
      protein kinases (MAPKs) signaling pathway in human multiple myeloma (MM) U266
      cells. We found that CBG caused the significant activation of ERK, JNK and p38
      MAPK in U266 cells. CBG showed much higher cytotoxicity against U266 cells as
      compared to peripheral blood mononuclear cells (PBMC). Induction of CBG increased
      reactive oxygen species (ROS) generation from mitochondria, which is associated
      with the induction of apoptosis as characterized by increased sub-G1 DNA contents
      of cell cycle, positive Annexin V binding, activation of caspase-3 and cleavage
      of PARP. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly
      prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis. CBG also
      down-regulated the expression of various downstream gene products that mediate
      cell proliferation, survival, angiogenesis and metastasis. Interestingly, ERK,
      JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation
      and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation
      and PARP cleavage in U266 cells. Taken together, these findings suggest that CBG
      can act as a potent anticancer agent against MM and possibly exerts its effects
      through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the
      activation of caspase-3 in U266 cells. 

PMID- 25982793
TI  - The academic penalty for gaining weight: a longitudinal, change-in-change
      analysis of BMI and perceived academic ability in middle school students.
AB  - BACKGROUND/OBJECTIVES: Worse educational outcomes for obese children regardless
      of academic ability may begin early in the life course. This study tested whether
      an increase in children's relative weight predicted lower teacher- and child
      perceived academic ability even after adjusting for standardized test scores.
      SUBJECTS/METHODS: Three thousand three hundred and sixty-two children
      participating in the Early Childhood Longitudinal Study-Kindergarten Cohort were
      studied longitudinally from fifth to eighth grade. Heights, weights, standardized
      test scores in maths and reading, and teacher and self-ratings of ability in
      maths and reading were measured at each wave. Longitudinal, within-child linear
      regression models estimated the impact of a change in body mass index (BMI) z
      score on change in normalized teacher and student ratings of ability in reading
      and maths, adjusting for test score. RESULTS: A change in BMI z-score from fifth
      to eighth grade was not independently associated with a change in standardized
      test scores. However, adjusting for standardized test scores, an increasing BMI z
      score was associated with significant reductions in teacher's perceptions of
      girls' ability in reading (-0.12, 95% confidence interval (CI): -0.23, -0.03,
      P=0.03) and boys' ability in math (-0.30, 95% CI: -0.43, -0.17, P<0.001). Among
      children who were overweight at fifth grade and increased in BMI z-score, there
      were even larger reductions in teacher ratings for boys' reading ability (-0.37,
      95% CI: -0.71, -0.03, P=0.03) and in girls' self-ratings of maths ability (-0.47,
      95% CI: -0.83, -0.11, P=0.01). CONCLUSIONS: From fifth to eighth grade, increase
      in BMI z-score was significantly associated with worsening teacher perceptions of
      academic ability for both boys and girls, regardless of objectively measured
      ability (standardized test scores). Future research should examine potential
      interventions to reduce bias and promote positive school climate.

PMID- 25982795
TI  - Acute liver injury attenuation of a novel recombinant sTNFR through blocking
      hepatic apoptosis.
AB  - CONTEXT: Tumor necrosis factor (TNF) alpha plays a key role in acute liver injury
      (ALI) induced by injection of d-galactosamine (D-Gal)/lipopolysaccharide (LPS). A
      novel recombinant trimeric sTNFRII, sTNFRII-gAD, has been tested to be effective
      in ameliorating ALI, when administered prior to ALI establishment. This study
      aims to validate the protective effect of sTNFRII-gAD when given after ALI setup
      and further explore its effect on hepatic apoptosis. MATERIALS AND METHODS: The
      treatments were carried out concomitantly with ALI establishment with clinically
      approved sTNFRII-Fc (the dimeric sTNFRII) as a positive control. Lethality, liver
      weight, and serum alanine transaminase were measured, and histological analysis
      was performed to evaluate liver injury induced by D-Gal/LPS. Additionally,
      Terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) and
      Western blot analyses of caspase-3 were used to examine hepatocellular apoptosis.
      RESULTS: sTNFRII-gAD given after D-Gal/LPS injection turned out to attenuate
      animal mortality significantly (p < 0.01), and had better hepatic protection. In
      terms of apoptosis, both sTNFRII-gAD and sTNFRII-Fc displayed noticeable
      improvement of apoptosis evidenced by dramatic decline of active caspase-3
      compared to the control group. CONCLUSIONS: The results demonstrated that sTNFRII
      gAD therapeutically diminished the lethality induced by D-Gal/LPS, possibly
      through blocking hepatic apoptosis initiated by TNFalpha. Of note, sTNFRII-gAD
      was superior to sTNFRII-Fc in some respects, indicating a promising alternative
      for the therapeutic strategy against the diseases associated with excessive
      TNFalpha.

PMID- 25982797
TI  - The critical molecular interconnections in regulating apoptosis and autophagy.
AB  - Apoptosis and autophagy are both highly regulated biological processes that have
      important roles in development, differentiation, homeostasis, and disease. These
      processes may take place independently, with autophagy being cytoprotective for
      preventing cells from apoptosis and apoptosis blocking autophagy. But in most
      circumstances, both may be induced sequentially with autophagy preceding
      apoptosis. The simultaneous activation of both processes has been observed not
      only in experimental settings but also in pathophysiological conditions. In fact,
      these two pathways are tightly connected with each other by substantial
      interplays between them, enabling the coordinated regulation of cell fates by
      these two pathways. They share some common upstream signaling components, and
      some components of one pathway may play important roles in the other, and vice
      versa. Such proteins represent the critical interconnections of the two pathways,
      which seem to determine the cell for survival or death. Here several critical
      molecular interconnections between apoptosis and autophagy pathways are reviewed,
      with their action mechanisms being highlighted. 

PMID- 25982796
TI  - Heme-mediated inhibition of Bach1 regulates the liver specificity and transience
      of the Nrf2-dependent induction of zebrafish heme oxygenase 1.
AB  - The induction of the gene encoding heme oxygenase 1 (Hmox1, HO-1) by Nrf2 is
      unique compared with other Nrf2 targets. We previously showed that the Nrf2a
      mediated induction of zebrafish hmox1a was liver specific and transient. We
      screened transcription factors that could repress the induction of hmox1a but not
      other Nrf2a targets and concluded that Bach1b was a prime candidate. In bach1b
      knocked-down larvae, the induction of hmox1a was observed ectopically in nonliver
      tissues and persisted longer than normal fish, suggesting that Bach1 is the only
      regulator for both the liver-specific and transient induction of hmox1a. Co
      knockdown of bach1b with its co-ortholog bach1a enhanced these effects. To
      determine why Bach1 could not repress the hmox1a induction in the liver, we
      analyzed the effects of a heme biosynthesis inhibitor, succinylacetone, and a
      heme precursor, hemin. Succinylacetone decreased the Nrf2a-mediated hmox1a
      induction, whereas pre-treatment with hemin caused ectopic induction of hmox1a in
      nonliver tissues, implying that the high heme levels in the liver may release the
      repressive activity of Bach1. Our results suggested that Bach1 regulates the
      liver specificity and transience of the Nrf2a-dependent induction of hmox1a and
      that heme mediates this regulation through Bach1 inhibition based on its level in
      each tissue. 

PMID- 25982798
TI  - Low anthropometric measures and mortality--results from the Malmo Diet and Cancer
      Study.
AB  - AIM: To study the association between anthropometric measures: body mass index
      (BMI), percent body fat, waist circumference (WC), waist-to-hip ratio (WHR),
      waist-to-height ratio (WHtR), waist-to-hip-to-height ratio (WHHR), and A Body
      Shape Index (ABSI); to see if individuals in the lowest 5 percentiles for these
      measures have an increased risk of mortality. METHODS: A population-based
      prospective cohort study (10,304 men and 16,549 women), the Malmo Diet and Cancer
      study (MDC), aged 45-73 years. RESULTS: During a mean follow-up of 14 +/- 3
      years, 2,224 men and 1,983 women died. There was a significant increased
      mortality risk after adjustments for potential confounders in the group with the
      5% lowest BMI (referent 25%-75%); hazard ratios (HR) with 95% confidence
      intervals were 1.33 (1.10-1.61) for women and 1.27 (1.07-1.52) for men. A similar
      significant increased mortality risk was seen with the 5% lowest percent body
      fat, HR 1.31 (1.07-1.60) for women and 1.25 (1.04-1.50) for men. Women with an
      ABSI in the lowest 5 percentiles had a lower mortality risk HR 0.64 (0.48-0.85).
      CONCLUSION: These results imply that BMI or percent body fat could be used to
      identify lean individuals at increased mortality risk.

PMID- 25982799
TI  - Role of tumor necrosis factor alpha in the pathogenesis of atrial fibrillation: A
      novel potential therapeutic target?
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice and a major cause of morbidity and mortality. Although the fundamental
      mechanisms underlying AF remain incompletely understood, atrial remodeling,
      including structural, electrical, contractile, and autonomic remodeling, has been
      demonstrated to contribute to the substrate for AF maintenance. Accumulating
      evidence shows that tumor necrosis factor alpha (TNF-alpha) plays exceedingly
      important roles in atrial remodeling. This article reviews recent advances in the
      roles of TNF-alpha in the pathogenesis of AF, elucidates the related mechanisms,
      and exploits its potential usefulness as a novel therapeutic target. 

PMID- 25982800
TI  - Reply to "Effectiveness and safety of extracranial carotid stent placement: A
      nationwide self-controlled case-series study".

PMID- 25982801
TI  - Prostate genetic score (PGS-33) is independently associated with risk of prostate
      cancer in the PLCO trial.
AB  - BACKGROUND: To investigate the ability of the prostate genetic score (PGS-33), a
      germ-line biomarker of prostate cancer (PCa) risk, to categorize men
      participating in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer
      Screening Trial. METHODS: We obtained the genetic data from the Cancer Genetic
      Markers of Susceptibility (CGEMS), a nested case control study examining germ
      line DNA in the screened arm of the PLCO trial. A PGS-33 was calculated based on
      their genotype at 33 PCa associated single nucleotide polymorphisms (SNPs). The
      primary outcome was the diagnosis of PCa and primary predictor was PGS-33.
      RESULTS: We identified 2,244 subjects (no cancer, N = 1017) and cases (N = 1227).
      The PGS-33 (P<0.001), prostate specific antigen (PSA; P < 0.001), family history
      of PCa (< 0.001), abnormal digital rectal exam (DRE, P < 0.001), and history of
      ever smoking (P = 0.037) were associated with a PCa diagnosis. In multivariable
      analysis, the log (PGS-33) was associated with PCa diagnosis with an odds ratio
      of 1.68 (95% CI 1.36-2.08, P < 0.001), log (PSA) (OR 8.2; 95% CI 6.75-10.04, P <
      0.001), and family history of PCa (OR 2.01; 95% CI 1.26-3.20, P = 0.003). PGS-33
      quartiles noted an increasing rate of PCa detection in addition to PSA: 43.2%
      (Q1), 47.8% (Q2), 58.8% (Q3), and 69.4 (Q4) (P < 0.001) and improvement in PSA
      performance (P < 0.001). CONCLUSIONS: Germ-line DNA in the form of the PGS-33 is
      able to risk stratify men regarding their risk of PCa. The PGS-33 may have
      implications regarding who may benefit most from PCa screening and possibly add
      to PSA performance.

PMID- 25982802
TI  - Predicting Hip Fracture Type With Cortical Bone Mapping (CBM) in the Osteoporotic
      Fractures in Men (MrOS) Study.
AB  - Hip fracture risk is known to be related to material properties of the proximal
      femur, but fracture prediction studies adding richer quantitative computed
      tomography (QCT) measures to dual-energy X-ray (DXA)-based methods have shown
      limited improvement. Fracture types have distinct relationships to predictors,
      but few studies have subdivided fracture into types, because this necessitates
      regional measurements and more fracture cases. This work makes use of cortical
      bone mapping (CBM) to accurately assess, with no prior anatomical presumptions,
      the distribution of properties related to fracture type. CBM uses QCT data to
      measure the cortical and trabecular properties, accurate even for thin cortices
      below the imaging resolution. The Osteoporotic Fractures in Men (MrOS) study is a
      predictive case-cohort study of men over 65 years old: we analyze 99 fracture
      cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly
      selected from 5994. To our knowledge, this is the largest QCT-based predictive
      hip fracture study to date, and the first to incorporate CBM analysis into
      fracture prediction. We show that both cortical mass surface density and
      endocortical trabecular BMD are significantly different in fracture cases versus
      cohort, in regions appropriate to fracture type. We incorporate these regions
      into predictive models using Cox proportional hazards regression to estimate
      hazard ratios, and logistic regression to estimate area under the receiver
      operating characteristic curve (AUC). Adding CBM to DXA-based BMD leads to a
      small but significant (p < 0.005) improvement in model prediction for any
      fracture, with AUC increasing from 0.78 to 0.79, assessed using leave-one-out
      cross-validation. For specific fracture types, the improvement is more
      significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 for trochanteric
      fractures and 0.76 to 0.82 for femoral neck fractures. In contrast, adding DXA
      based BMD to a CBM-based predictive model does not result in any significant
      improvement.

PMID- 25982803
TI  - The Effect of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy Surgery on Dietary
      Intake, Food Preferences, and Gastrointestinal Symptoms in Post-Surgical Morbidly
      Obese Lebanese Subjects: A Cross-Sectional Pilot Study.
AB  - BACKGROUND: Data on gastrointestinal (GI) and dietary changes following bariatric
      surgery are scarce in the Middle Eastern region. The objective of this work was
      to retrospectively compare dietary intake, food preferences, and GI symptoms in
      subjects with extreme obesity after Roux-en-Y gastric bypass (RYGB) and sleeve
      gastrectomy (SG). METHODS: Sixty subjects equally divided between RYGB and SG
      with a postoperative period of >=6 months were recruited for a retrospective, non
      randomized, and observational study. All subjects completed three questionnaires
      (GI symptoms, food preferences, and quantitative food frequency questionnaire
      (FFQ)) and three 24-h recalls. RESULTS: At one year postoperatively, both
      surgical groups showed similar percentage of excess weight loss that exceeded
      50%. In addition, percentage of carbohydrate, protein, and sugar intake from
      total energy, frequency of daily consumption from the eight food categories and
      daily energy intake were comparable between surgical groups. RYGB subjects
      consumed significantly more fruits and juices from total energy (P < 0.05)
      whereas SG subjects tended to consume more sweets and desserts. Heartburn (P <
      0.001), regurgitation (P < 0.01), nausea (P < 0.01), vomiting (P < 0.001), and
      constipation (P < 0.05) were significantly more frequent among SG subjects.
      Flatulence (P < 0.001) and diarrhea (P < 0.05), as well as dizziness (P < 0.001),
      and fast heartbeat (P < 0.05) after eating were significantly more frequent after
      RYGB. CONCLUSIONS: There were no major differences in dietary intake and food
      preferences between RYGB and SG groups. There was a trend for sweet-eating in SG
      subjects with less dumping symptoms to suggest different mechanisms of action for
      each procedure, which might impact eating behavior.

PMID- 25982804
TI  - Dual Intragastric Balloon: Single Ambulatory Center Spanish Experience with 60
      Patients in Endoscopic Weight Loss Management.
AB  - BACKGROUND: Many obese patients fail conventional medical management and decline
      bariatric surgery. Less invasive weight loss options such as intragastric
      balloons may provide an opportunity to reach this large number of untreated
      patients. The aim of this study was to investigate the safety and effectiveness
      of the Dual Intragastric Balloon (DIGB) in the treatment of obese patients, as
      well as the impact of degree of obesity, age, and gender. METHODS: The study was
      conducted at the Bariatric Endoscopy Unit of the Madrid Sanchinarro University
      Hospital. Sixty patients (11 men, 49 women) underwent endoscopic placement of a
      DIGB filled with a total of 900 cc of saline (450 cc in each balloon) for at
      least 6 months, along with regular counseling from a multidisciplinary team.
      Study outcomes included: change in body weight (TBWL), % of loss of initial body
      weight (%TBWL), % of excess body weight loss (%EWL), and adverse events. RESULTS:
      Initial BMI 38.8 kg/m(2) decreased 6.1 units, with mean TBWL, %TBWL, and %EWL of
      16.6 kg, 15.4 %, and 47.1 %, respectively. We found no difference in %TBWL
      between grade of obesity, age or sex, but morbidly obese patients demonstrated
      greater TBWL, and women and less obese subjects obtained higher %EWL. The DIGB
      was generally well tolerated, with one early removal for patient intolerance, one
      early deflation without migration, and one gastric perforation. Fourteen patients
      had small, clinically insignificant ulcers or erosions noted at the time of
      removal. CONCLUSIONS: The present study shows that the DIGB was easy to use,
      resulted in significant weight loss, safe, and well tolerated.

PMID- 25982805
TI  - Biliopancreatic Diversion for Severe Obesity: Long-Term Effectiveness and
      Nutritional Complications.
AB  - BACKGROUND: Bariatric surgery is currently the treatment of choice for those
      patients with severe obesity, but the procedure of choice is not clearly
      established. We describe weight loss and nutritional parameters in severely obese
      patients after biliopancreatic diversion for 10 years of follow-up. METHODS:
      Patients were followed by the same multidisciplinary team, and data are shown for
      10 years. Bariatric Analysis and Reporting Outcome System (BAROS) questionnaire,
      data regarding the evolution of obesity-related diseases, and nutritional
      parameters are reported. RESULTS: Two hundred ninety-nine patients underwent
      biliopancreatic diversion, 76.1 % women, initial BMI 50.1 kg/m(2) (7.2). Weight
      loss was maintained throughout 10 years with EWL% around 65 % and EBMIL% around
      70 %. More than 80 % of the patients showed EWL higher than 50 %. Blood pressure,
      glucose metabolism, and lipid profile clearly improved after surgery. Mean
      nutritional parameters remained within the normal range during follow-up. Protein
      malnutrition affected less than 4 % and anemia up to 16 %. Fat-soluble vitamin
      levels decreased along the time, with vitamin D deficiency in 61.5 % of patients.
      No significant differences were found either in nutritional parameters or weight
      loss regarding gastrectomy or gastric preservation, or common limb length longer
      or shorter than 55 cm CONCLUSIONS: Biliopancreatic diversion is an effective
      surgical procedure in terms of weight loss, quality of life, and evolution of
      obesity-related diseases. Nutritional deficiencies are less frequent than feared
      for a malabsorptive procedure, but must be taken into account, especially for fat
      soluble vitamins.

PMID- 25982808
TI  - Stereoselective synthesis of organosulfur compounds incorporating N-aromatic
      heterocyclic motifs and quaternary carbon centers via a sulfa-Michael triggered
      tandem reaction.
AB  - A novel sulfa-Michael addition (SMA)-triggered tandem reaction was developed by
      combining a SMA reaction with a simultaneous rearomatization process utilizing a
      less reactive carbonyl group as an intramolecular electrophile partner, which
      provided a unique synthetic route to access various organosulfur compounds
      incorporating an N-aromatic heterocyclic motif and quaternary carbon centers. 

PMID- 25982807
TI  - A Systematic Review of Bariatric Surgery in Patients with Liver Cirrhosis.
AB  - Nonalcoholic steatohepatitis is becoming a common cause of liver cirrhosis and a
      significant number of patients undergoing bariatric surgery suffer with it. There
      is currently lack of consensus among surgeons regarding safety of bariatric
      surgery in patients with liver cirrhosis and the best bariatric procedure in
      these patients. This review investigates published English language scientific
      literature systematically in an attempt to answer these questions. Eleven studies
      that reported experience of bariatric surgery in cirrhotic obese patients were
      included in this review. This review shows an acceptably higher overall risk of
      complications and perioperative mortality with bariatric surgery in cirrhotic
      patients. Surgeons must discuss the possibility of an unexpected intraoperative
      diagnosis of cirrhosis preoperatively with all bariatric surgery patients and
      agree on a course of action. 

PMID- 25982806
TI  - Changes in Bone Metabolism in Morbidly Obese Patients After Bariatric Surgery: A
      Meta-Analysis.
AB  - BACKGROUND: The aim is to evaluate via meta-analysis bone metabolism and bone
      mineral density (BMD) in morbidly obese patients before and after bariatric
      surgery. METHODS: We searched Medline, EMBASE, and the Cochrane Library for
      relevant studies published before January 2014. The following outcomes were
      evaluated: serum calcium, serum parathyroid hormone (PTH), serum 25
      hydroxyvitamin D [25(OH)D], serum or urinary N-telopeptide (NTX), bone-specific
      alkaline phosphatase (BSAP), and bone mineral density (BMD). RESULTS: Ten
      studies, including 344 patients, met our inclusion criteria. Results showed a
      significant decrease in serum calcium (MD = -0.10, 95 %CI -0.14 to -0.07, P <
      0.00001) and increase in serum PTH (MD = 12.41, 95 %CI 6.51 to 18.31, P <
      0.00001) but no significant difference in serum 25(OH)D (MD = 1.35, 95 %CI -1.12
      to 3.83, P = 0.28) following bariatric surgery. There were significant increases
      in serum or urinary NTX (MD = 18.49, 95 %CI 3.33 to 33.66, P = 0.02) and BSAP (MD
      = 7.47, 95 %CI 0.21 to 14.72, P = 0.04) but a significant decrease in BMD (MD = 
      0.08, 95 %CI -0.13 to -0.04, P < 0.00001) after bariatric surgery. CONCLUSION:
      BMD was significantly decreased, while bone turnover was elevated, and bone
      remodeling was accelerated following bariatric surgery. Basal bone metabolism
      should be evaluated preoperatively. To prevent secondary hyperparathyroidism and
      bone loss, calcium and vitamin D should be monitored closely and supplemented
      accordingly after the surgery.

PMID- 25982809
TI  - Physicochemical characteristics and desulphurization activity of pyrolusite
      blended activated coke.
AB  - In this study, a novel activated coke (AC-P) was prepared by the blending method
      using bituminous coal as the raw material and pyrolusite as the catalyst. The
      physicochemical properties of prepared activated coke (AC) were characterized by
      BET, Fourier-Transform Infrared Spectroscopy, X-ray photoelectron spectroscopy
      and X-ray diffraction. The results indicated that the blended pyrolusite had a
      slight effect on the structural properties of AC, while the oxygenated functional
      groups on AC were increased and MnO2 and Fe2O3 in pyrolusite were reduced to MnO
      and Fe on the AC-P samples, respectively. All the AC-P samples significantly
      improved the removal of SO2, with the highest sulphur capacity (153 mg/g) for the
      AC blended with 8 wt% pyrolusite, which was 57.7% higher than that of the blank
      activated cock. This could be mainly attributed to the change in surface chemical
      properties of the AC-P samples and the active catalytic components in pyrolusite
      for the catalytic oxidation of SO2 in desulphurization process. 

PMID- 25982810
TI  - Longitudinal investigation of the relationship between family history of
      psychosis and affective disorders and Child Behavior Checklist ratings in
      clinical high-risk adolescents.
AB  - This is the first study to investigate whether positive family history (FH) of
      psychosis and affective disorders moderates the relationship between child
      diagnostic status and parent-reported social and behavioral problems on the Child
      Behavior Checklist (CBCL) in clinical high-risk adolescents. This longitudinal
      investigation assessed 122 participants (mean age=14.25+/-1.8years) from three
      groups (at-risk, other personality disorders, non-psychiatric controls) at
      baseline and one year follow-up. As predicted, there was a main effect of FH for
      a number of CBCL scales indicating higher scores for adolescents with positive
      FH. The findings also demonstrate a significant Diagnostic Status*Family History
      interaction for several behavioral scales providing support for FH as a
      concurrent and longitudinal moderator of the relationship between diagnostic
      status and CBCL scales. The moderating effect is present for areas of functioning
      associated with depression, anxiety, social adjustment, thought problems,
      attention problems, and aggressive behavior. The findings also indicate that both
      positive and negative symptoms are related to the genetic vulnerability for
      developing psychosis in clinical high-risk individuals, particularly those
      symptoms reflective of emotional, attentional, and interpersonal functioning. The
      present findings are novel and have significant clinical and research
      implications. This investigation provides a platform for future studies to
      clarify further the role of FH in clinical high-risk individuals and contributes
      to integration of this knowledge in the development of early intervention and
      prevention approaches in at-risk populations for the emergence of severe mental
      illness.

PMID- 25982811
TI  - Motivational deficits in early schizophrenia: prevalent, persistent, and key
      determinants of functional outcome.
AB  - Negative symptoms, in particular motivational deficits, are reported as
      impediments to functional recovery in patients with schizophrenia. This study
      examined the prevalence of motivational deficits in patients early in the
      illness, and the impact these deficits have on community functioning. Patients
      with schizophrenia between the ages of 18 and 35years, and within 5years of
      initiating antipsychotic treatment were included in the present investigation
      (N=166). The impact of motivation and cognition on concurrent and longitudinal
      functioning was evaluated. Motivational impairments were found in more than 75%
      of participants, and were not associated with receipt of social support. These
      deficits served as the most robust and reliable predictor of functional outcome,
      while neurocognition demonstrated significantly weaker associations with outcome.
      When considered together, motivational deficits demonstrated a reliable link with
      concurrent and longitudinal functioning, with cognition not offering any
      independent predictive value. Moreover, motivation was found to mediate the
      relationship between cognition and outcome. Changes in motivation were linked to
      changes in functioning; however, this was not the case for changes in cognitive
      performance. Motivation emerged as a significant predictor of functioning even
      after selected demographic and clinical characteristics (e.g., positive symptoms)
      were accounted for. These data indicate that motivational deficits are prevalent
      in patients with schizophrenia, even in the early stages of the illness, and
      these deficits stand as one of the most robust barriers to people with
      schizophrenia achieving functional recovery. Greater understanding of the
      mechanisms underlying these deficits is critical to effective treatment
      innovation. 

PMID- 25982812
TI  - Possibilities and challenges of online, social media, and mobile technologies for
      psychosis treatment.

PMID- 25982813
TI  - Free thyroxine levels are associated with cognitive abilities in subjects with
      early psychosis.
AB  - INTRODUCTION: Subjects with a psychotic disorder show mild to moderate cognitive
      impairment, which is an important determinant of functional outcome. The
      underlying biological process of cognitive impairment in psychosis is unclear. We
      aimed to explore whether hypothalamic-pituitary-thyroid axis hormones or thyroid
      autoimmunity modulate cognitive functioning in subjects with early psychosis.
      METHODS: We studied 70 patients with a psychotic disorder (<3years of illness)
      and a control group of 37 healthy subjects (HS). Plasma levels of thyroid
      stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs)
      and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was
      performed with the MATRICS Cognitive Consensus Cognitive Battery. We also
      explored the relationship between thyroid variables and cognition in three
      subgroups of psychotic patients: psychosis not otherwise specified, affective
      psychosis (bipolar disorder or schizoaffective disorder) and non-affective
      psychosis (schizophrenia or schizophreniphorm disorder). RESULTS: In patients
      with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were
      associated with better cognitive performance in attention/vigilance and overall
      cognition. The relationship between FT4 levels and the attention/vigilance domain
      remained significant in a multivariate analysis after adjusting for education
      level, age, gender, substance use, and benzodiazepine and antipsychotic
      treatments. We did not find a significant association between FT4 and cognitive
      performance in HS. In the exploratory analysis by psychotic subtypes, subjects
      with affective psychosis had increased FT4 levels and better cognitive profile
      than those with non-affective psychosis. CONCLUSIONS: Our study suggests that FT4
      levels are associated with cognitive abilities (attention/vigilance and overall
      cognition) in individuals with early psychosis.

PMID- 25982816
TI  - The TGF-beta Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to
      Bone.
AB  - Transforming growth factor-beta (TGF-beta) regulates the expression of genes
      supporting breast cancer cells in bone, but little is known about prostate cancer
      bone metastases and TGF-beta. Our study reveals that the TGFBR1 inhibitor SD208
      effectively reduces prostate cancer bone metastases. TGF-beta upregulates in
      prostate cancer cells a set of genes associated with cancer aggressiveness and
      bone metastases, and the most upregulated gene was PMEPA1. In patients, PMEPA1
      expression decreased in metastatic prostate cancer and low Pmepa1 correlated with
      decreased metastasis-free survival. Only membrane-anchored isoforms of PMEPA1
      interacted with R-SMADs and ubiquitin ligases, blocking TGF-beta signaling
      independently of the proteasome. Interrupting this negative feedback loop by
      PMEPA1 knockdown increased prometastatic gene expression and bone metastases in a
      mouse prostate cancer model. 

PMID- 25982817
TI  - Repression by H-NS of genes required for the biosynthesis of the Vibrio cholerae
      biofilm matrix is modulated by the second messenger cyclic diguanylic acid.
AB  - Expression of Vibrio cholerae genes required for the biosynthesis of
      exopolysacchide (vps) and protein (rbm) components of the biofilm matrix is
      enhanced by cyclic diguanylate (c-di-GMP). In a previous study, we reported that
      the histone-like nucleoid structuring (H-NS) protein represses the transcription
      of vpsA, vpsL and vpsT. Here we demonstrate that the regulator VpsT can disrupt
      repressive H-NS nucleoprotein complexes at the vpsA and vpsL promoters in the
      presence of c-di-GMP, while H-NS could disrupt the VpsT-promoter complexes in the
      absence of c-di-GMP. Chromatin immunoprecipitation-Seq showed a remarkable trend
      for H-NS to cluster at loci involved in biofilm development such as the rbmABCDEF
      genes. We show that the antagonistic relationship between VpsT and H-NS regulates
      the expression of the rbmABCDEF cluster. Epistasis analysis demonstrated that
      VpsT functions as an antirepressor at the rbmA/F, vpsU and vpsA/L promoters.
      Deletion of vpsT increased H-NS occupancy at these promoters while increasing the
      c-di-GMP pool had the opposite effect and included the vpsT promoter. The
      negative effect of c-di-GMP on H-NS occupancy at the vpsT promoter required the
      regulator VpsR. These results demonstrate that c-di-GMP activates the
      transcription of genes required for the biosynthesis of the biofilm matrix by
      triggering a coordinated VpsR- and VpsT-dependent H-NS antirepression cascade. 

PMID- 25982819
TI  - Forensic age estimation through evaluation of the apophyseal ossification of the
      iliac crest in Western Chinese.
AB  - The criminal age estimation procedures have gained greatest significance to date,
      a reliable age diagnostics may depend on data of skeletal maturation from
      different socioeconomic status. In order to establish the iliac crest apophysis
      as a possible criterion for forensic age estimation in a different socioeconomic
      status, and to examine the pace of ossification for the iliac crest apophysis in
      Western Chinese, one thousand seven hundreds and seventy-seven conventional
      pelvic radiographs relating to West China Han group routinely taken between
      January 2010 and June 2012 have been sighted. The data was analysed with
      separation of the sexes. The results indicated that stage 2a was last observed in
      females at the age of 17.00 and in males at the age of 18.01, stage 3a was first
      achieved in females at the age of 14.46 and in males at the age of 15.31, stage 4
      was observed between 17.95 and 25.98 years for male and between 18.36 and 25.95
      years for female. By comparison with previous studies, our research indicated
      that Western Chinese presents a delaying development for the iliac crest
      apophysis. Furthermore, the present study with eight stages of ossification for
      the iliac crest offers a valuable alternative method of estimation of 18 years of
      age for Western Chinese. 

PMID- 25982818
TI  - Stabilization of proteins in solid form.
AB  - Immunogenicity of aggregated or otherwise degraded protein delivered from depots
      or other biopharmaceutical products is an increasing concern, and the ability to
      deliver stable, active protein is of central importance. We review
      characterization approaches for solid protein dosage forms with respect to
      metrics that are intended to be predictive of protein stability against
      aggregation and other degradation processes. Each of these approaches is
      ultimately motivated by hypothetical connections between protein stability and
      the material property being measured. We critically evaluate correlations between
      these properties and stability outcomes, and use these evaluations to revise the
      currently standing hypotheses. Based on this we provide simple physical
      principles that are necessary (and possibly sufficient) for generating solid
      delivery vehicles with stable protein loads. Essentially, proteins should be
      strongly coupled (typically through H-bonds) to the bulk regions of a phase
      homogeneous matrix with suppressed beta relaxation. We also provide a framework
      for reliable characterization of solid protein forms with respect to stability. 

PMID- 25982820
TI  - Assessing trace element contamination in Fildes Peninsula (King George Island)
      and Ardley Island, Antarctic.
AB  - King George Island, situated in the South Shetland Islands archipelago, is one of
      the most visited sites in Antarctica. This has contributed to a high density of
      scientific stations and shelters in the region, especially in Fildes Peninsula.
      In order to evaluate the natural and anthropogenic sources of trace elements (As,
      Cd, Cu, Zn, Pb and Hg) soil and moss samples were collected from different sites
      in January 2013. In general, the results revealed homogeneous concentrations
      (MUgg(-)(1)) for each element in the majority of collected samples (As: 3.8+/
      1.4; Cd: 0.4+/-0.9; Cu: 34+/-4; Zn: 115+/-13; Pb: 20+/-5; Hg; 0.011+/-0.009).
      However, some samples in specific areas of Fildes Bay showed the existence of
      local anthropogenic activities that have contributed to the enrichment of
      contaminants in soils and moss samples that correlated to one another (e.g. Pb:
      1101MUgg(-)(1)). Human presence is linked to examples of contamination and
      environmental perturbation, making essential the implementation of this type of
      study in order to understand and protect unique places in Antarctica. 

PMID- 25982821
TI  - Stable isotope variations in benthic primary producers along the Bosphorus
      (Turkey): A preliminary study.
AB  - The Bosphorus Strait is a dynamic and complex system. Recent evidences showed
      nitrogen and heavy metal concentrations to follow opposite patterns across the
      Strait, suggesting a complex spatial organisation of the anthropogenic
      disturbance in this system. Here, we provide isotopic information on the origin
      and transportation of dissolved nitrogen along the Bosphorus. C and N isotopic
      and elemental analyses were performed on specimens of Ulva lactuca and associated
      epiphytes sampled in five locations across the Strait. Variations in C and N
      isotopic signatures were observed in U. lactuca, pointing to a decrease in the
      availability of anthropogenic organic dissolved nitrogen along a north-south
      direction. Conversely, epiphytes did not show isotopic or elemental patterns
      across the Strait. These results suggest that preliminary stable isotope surveys
      in extended costal systems basing on U. lactuca can represent a valuable tool to
      focus meaningful targets and hypotheses for pollution studies in the
      Mediterranean region. 

PMID- 25982822
TI  - Association of circulating levels of neopterin with non-culprit plaque
      vulnerability in CAD patients an angiogram, optical coherent tomography and
      intravascular ultrasound study.
AB  - BACKGROUND: Neopterin is a pteridine derivative secreted by activated
      macrophages. Previous studies have shown that neopterin plays a pivotal role in
      coronary artery disease (CAD); however, the relationship between circulating
      neopterin and non-culprit plaque vulnerability in patients with CAD remains
      unclear. In this study, we investigated the correlation of neopterin and
      vulnerable plaque features in patients with CAD. METHODS: One hundred and thirty
      non-culprit plaques from 81 patients with CAD were assessed by angiogram and
      optical coherence tomography (OCT) as well as intravascular ultrasound (IVUS)
      imaging. According to the median value of serum neopterin (10.61 nmol/L),
      patients were divided into a low neopterin group (n = 40, <median) and a high
      neopterin group (n = 41, >=median). Plaque characteristics were compared between
      the two groups. RESULTS: Compared with the low neopterin group, OCT findings
      showed that patients in the high neopterin group had thinner fibrous cap
      thickness (FCT) (90.02 +/- 52.96 MUm vs. 124.69 +/- 65.23 MUm, P = 0.004) and
      more thin-cap fibroatheroma (TCFA) (38.0% vs. 13.6%, P = 0.002). Microvessel and
      plaque rupture were more frequently observed in the high neopterin group (P =
      0.004 and P = 0.005, respectively). IVUS findings showed that plaque burden was
      greater in the high neopterin group than that in the low neopterin group (P =
      0.005). CONCLUSIONS: Neopterin was positively associated with vulnerable plaque
      features including TCFA, thinner fibrous cap, plaque rupture, greater plaque
      burden and frequent microvessel occurrence in CAD patients.

PMID- 25982823
TI  - Flow-mediated dilation: An evolving method.

PMID- 25982824
TI  - Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and
      Hypertrophy Caused by Chronic Pressure Overload.
AB  - BACKGROUND: Caloric restriction (CR) prevents senescent changes, in which
      reactive oxygen species (ROS) have a critical role. Left ventricular (LV)
      hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR
      alters cardiac redox state and hypertrophy from chronic pressure overload.
      METHODS AND RESULTS: Male c57BL6 mice were subjected to ascending aortic
      constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40%
      restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC
      and was continued for 4 weeks. Two weeks after constriction, AAC increased LV
      wall thickness, impaired transmitral flow velocity, and augmented myocyte
      hypertrophy and fibrosis, in association with enhancement of BNP and collagen III
      expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in
      cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and
      mitochondrial ROS production were elevated. These changes were significantly
      attenuated in the CR + AAC group. Additionally, in antioxidant systems,
      myocardial glutathione peroxidase and superoxide dismutase activities were
      enhanced in the CR + AAC group. CONCLUSIONS: Chronic pressure overload increased
      cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis.
      Short-term CR suppressed oxidative stress and improved cardiac function,
      suggesting that short-term CR could be a useful strategy to prevent pressure
      overload-induced cardiac injury.

PMID- 25982825
TI  - The Importance of NLRP3 Inflammasome in Heart Failure.
AB  - Patients with heart failure continue to suffer adverse health consequences
      despite advances in therapies over the past 2 decades. Identification of novel
      therapeutic targets that may attenuate disease progression is therefore needed.
      The inflammasome may play a central role in modulating chronic inflammation and
      in turn affecting heart failure progression. The inflammasome is a complex of
      intracellular interaction proteins that trigger maturation of proinflammatory
      cytokines interleukin-1beta and interleukin-18 to initiate the inflammatory
      response. This response is amplified through production of tumor necrosis factor
      alpha and activation of inducible nitric oxide synthase. The purpose of this
      review is to discuss recent evidence implicating this inflammatory pathway in the
      pathophysiology of heart failure. 

PMID- 25982826
TI  - Nurse-Enhanced Computerized Cognitive Training Increases Serum Brain-Derived
      Neurotropic Factor Levels and Improves Working Memory in Heart Failure.
AB  - BACKGROUND: Memory loss is common in heart failure (HF) patients, but few
      interventions have been tested to treat it. The objective of this study was to
      evaluate efficacy of a cognitive training intervention, Brain Fitness, to improve
      memory, serum brain-derived neurotropic factor (BDNF) levels, working memory,
      processing speed, executive function, instrumental activities of daily living,
      mobility, depressive symptoms, and health-related quality of life. METHODS AND
      RESULTS: Twenty-seven HF patients were randomly assigned to Brain Fitness and
      health education active control interventions. Data were collected at baseline
      and 8 and 12 weeks. Linear mixed models analyses were completed. Patients in the
      Brain Fitness group were older with lower ejection fraction. At 12 weeks, a group
      by time interaction effect was found for serum BDNF levels (P = .011): serum BDNF
      levels increased among patients who completed Brain Fitness and decreased among
      patients who completed health education. No differences were found in memory, but
      a group by time interaction (P = .046) effect was found for working memory.
      CONCLUSIONS: Findings support efficacy of Brain Fitness in improving working
      memory and serum BDNF levels as a biomarker of intervention response. A
      randomized controlled study is needed among a larger more diverse group of HF
      patients.

PMID- 25982827
TI  - Association of Hypocalcemia With Mortality in Hospitalized Patients With Heart
      Failure and Chronic Kidney Disease.
AB  - BACKGROUND: Chronic kidney disease--mineral and bone disorders (CKD-MBD) are
      associated with vascular calcification and abnormal electrolytes that lead to
      cardiovascular disease and mortality. CKD-MBD is identified by imbalances in
      serum calcium (Ca), phosphate, and parathyroid hormone (PTH). Although the
      relation of phosphate and PTH with the prognosis of HF patients has been
      reported, the association of Ca with prognosis in patients with heart failure
      (HF) and CKD remains unclear. METHODS AND RESULTS: We examined 191 patients
      admitted for HF and CKD (estimated glomerular filtration rate <60 mL min(-1) 1.73
      m(-2)), and they were divided into 2 groups based on levels of corrected Ca: low
      Ca (Ca <8.4 mg/dL; n = 32) and normal-high Ca (8.4 <=Ca; n = 159). We compared
      laboratory and echocardiographic findings, as well as followed cardiac and all
      cause mortality. The low-Ca group had 1) higher levels of alkaline phosphatase
      (308.9 vs. 261.0 U/L; P = .026), 2) lower levels of 1,25-dihydroxy vitamin D
      (26.1 vs. 45.0 pg/mL; P = .011) and hydrogen carbonate (22.4 vs. 24.5 mmol/L; P =
      .031), and 3) a tendency to have a higher PTH level (87.5 vs. 58.6 pg/mL; P =
      .084). In contrast, left and right ventricular systolic function, estimated
      glomerular filtration rate, urine protein, phosphate, sodium, potassium,
      magnesium, and zinc did not differ between the 2 groups. In the Kaplan-Meier
      analysis, cardiac and all-cause mortality were significantly higher in the low-Ca
      group than in the normal-high-Ca group (P < .05). In the multivariable Cox
      proportional hazard analyses, hypocalcemia was an independent predictor of all
      cause mortality in HF and CKD patients (P < .05). CONCLUSIONS: Hypocalcemia was
      an independent predictor of all-cause mortality in HF and CKD patients.

PMID- 25982828
TI  - [Allopurinol-induced DRESS complicated by hemophagocytic lymphohistiocytosis].
AB  - BACKGROUND: Drug hypersensitivity syndrome is among the most severe drug
      hypersensitivity reactions and in rare cases it may progress to hemophagocytic
      lymphohistiocytosis. Herein, we report a case of allopurinol-induced drug
      reaction with eosinophilia and systemic symptoms complicated by hemophagocytic
      lymphohistiocytosis. CASE REPORT: An 18-year-old girl presented with
      maculopapular rash associated with cervical lymphadenopahy appearing 3 weeks
      after treatment with allopurinol. Her hemodynamic status at admission was
      unstable. Cutaneous examination revealed an itchy maculopapular rash, which was
      purpuric at certain sites, together with facial edema. The diagnosis of drug
      hypersensitivity was suggested and was confirmed by histological examination of a
      skin biopsy. Allopurinol was stopped. Two weeks later, however, eosinophilia was
      noted. Further, four days after discontinuation of allopurinol, in view of the
      laboratory signs of bicytopenia, hyponatremia, hypertriglyceridemia and
      hyperferritinaemia, as well as the presence of hemophagocytosis in bone marrow, a
      diagnosis was made of lymphohistiocytosis hemophagocytic syndrome complicating a
      drug reaction with eosinophilia and systemic symptoms. Moreover, viral serology
      tests were negative. The patient was given intravenous immunoglobulin and the
      outcome was good. DISCUSSION: The literature contains only very few reports of
      drug reaction with eosinophilia and systemic symptoms complicated by
      hemophagocytic lymphohistiocytosis. The incriminated drugs were vancomycin,
      lamotrigine and phenobarbital. To our knowledge, there has only been one report
      of allopurinol-induced drug reaction with eosinophilia and systemic symptoms
      complicated by hemophagocytic lymphohistiocytosis.

PMID- 25982829
TI  - Translating Cognitive Behavioral Therapy for Anxious Youth to Rural-Community
      Settings via Tele-Psychiatry.
AB  - This study aimed to determine the feasibility of translating cognitive behavioral
      therapy for anxious youth to rural-community settings via tele-psychiatry
      training. A 20-week group-supervision training program was delivered to ten
      different groups from different agencies within Northern Ontario. Each group
      consisted of four to nine clinicians with child therapy background not specific
      to CBT (n = 78, 51% social workers, 49% other mental health disciplines).
      Clinicians were each required to treat an anxious youth under supervision.
      Changes in clinician knowledge and youth internalizing symptoms were measured.
      Northern Ontario clinicians showed significant gains on a child CBT-related
      knowledge test (t (1, 52) = -4.6, p < .001). Although youth treated by these
      clinicians showed a significant decrease in anxiety symptoms, possible response
      bias and the lack of a comparison group mandate further studies before
      generalizing our findings. Nevertheless, training local therapists in anxiety
      focused CBT for children via a group supervision based tele-psychiatry model
      appears to be a feasible and well-received approach to knowledge translation to
      rural settings.

PMID- 25982830
TI  - Leadership and Licensure for Drug Treatment and the Implementation of Co
      Occurring Disorder Treatment in Community Mental Health Centers.
AB  - Using a random sample of 48 outpatient mental health programs in low-income and
      racial and ethnic minority communities, this study examined directorial
      leadership, drug treatment licensure, and implementation of evidence-based
      protocols and practices to address co-occurring mental health and substance abuse
      disorders (COD). Understanding of findings was enhanced with focus groups at six
      clinics. Most programs (81 %) offered COD treatment. Directorial leadership was
      positively associated with COD treatment (beta = 0.253, p = 0.047, 95 % CI 0.003,
      0.502) and COD supervision and training (beta = 0.358, p = 0.002, 95 % CI 0.142,
      0.575). Licensure was negatively associated with COD treatment (beta = -0.235, p
      = 0.041, 95 % CI -0.460, -0.010) and COD supervision and training (beta = -0.195,
      p = 0.049, 95 % CI -0.389, -0.001). Although lack of financial integration may
      limit the effect of licensing on COD treatment implementation, the response of
      leaders to regulation, funding, and human resources issues may encourage COD
      treatment practices. Implications for leadership interventions and policy are
      discussed in the context of health care reform.

PMID- 25982831
TI  - Does Gender Explain the Relationship Between Occupation and Suicide? Findings
      from a Meta-Analytic Study.
AB  - This report investigated whether suicide risk by occupational groups differed for
      males and females. We examined this using a sub-set of articles examined in a
      recent meta-analysis and stratified by gender. For certain occupational groups,
      males and females had a similar risk of suicide (the military, community service
      occupations, managers, and clerical workers). There was some indication of gender
      differences for other occupations (technicians, plant and machine operators and
      ship's deck crew, craft and related trades workers, and professionals), although
      these did not reach statistical significance. These findings highlight the
      complexity of the relationship between occupation and suicide and suggest the
      possible role of a range of individual, work-related and social-environmental
      risk factors that may differ for males and females.

PMID- 25982832
TI  - Impact of the Syrian Crisis on the Hospitalization of Syrians in a Psychiatric
      Setting.
AB  - Determine the impact of the Syrian crisis on the hospitalization of Syrians in a
      psychiatric setting. All Syrians admitted to a psychiatric hospital in Lebanon
      between the 1st of January 2009 and the 31st of December 2013 were included.
      Number of admissions, psychiatric disorders and demographic and clinical data
      relative to patients were compared between those admitted before and after the
      crisis. 44 patients were admitted before the crisis and 106 after it. The
      distribution of diagnosis varied significantly after the crisis (p = 0.056) with
      the majority of patients being admitted for schizophrenia (37.7 %). The
      prevalence of suicidal ideation was higher after the crisis (p = 0.03) but
      suicidal attempts, need for electroconvulsive therapy and length of
      hospitalization did not differ significantly between both groups. Clinicians
      should be aware of the possible burden of mental illness in Syrians after the
      beginning of the Syrian crisis. 

PMID- 25982833
TI  - Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to
      cocaine within the reward circuit.
AB  - The subthalamic nucleus (STN) is a critical component of a complex network
      controlling motor, associative and limbic functions. High-frequency stimulation
      (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian
      patients and can also reduce their treatment-induced addictive behaviors.
      Preclinical studies have shown that STN HFS decreases motivation for cocaine
      while increasing that for food, highlighting its influence on rewarding and
      motivational circuits. However, the cellular substrates of these effects remain
      unknown. Our objectives were to characterize the cellular consequences of STN HFS
      with a special focus on limbic structures and to elucidate how STN HFS may
      interfere with acute cocaine effects in these brain areas. Male Long-Evans rats
      were subjected to STN HFS (130 Hz, 60 MUs, 50-150 MUA) for 30 min before an acute
      cocaine injection (15 mg/kg) and sacrificed 10 min following the injection.
      Neuronal reactivity was analyzed through the expression of two immediate early
      genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN
      HFS only activated c-Fos in the globus pallidus and the basolateral amygdala,
      highlighting a possible role on emotional processes via the amygdala, with a
      limited effect by itself in other structures. Interestingly, and despite some
      differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos
      response induced by acute cocaine in the striatum. By preventing the cellular
      effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing
      properties of the drug, which is in line with the inhibitory effect of STN HFS on
      the rewarding and reinforcing properties of cocaine.

PMID- 25982834
TI  - Unexpected cellular players in Rett syndrome pathology.
AB  - Rett syndrome is a devastating neurodevelopmental disorder, primarily caused by
      mutations of methyl CpG-binding protein 2 (MeCP2). Although the genetic cause of
      disease was identified over a decade ago, a significant gap still remains in both
      our clinical and scientific understanding of its pathogenesis. Neurons are known
      to be primary players in pathology, with their dysfunction being the key in Rett
      syndrome. While studies in mice have demonstrated a clear causative - and
      potential therapeutic - role for neurons in Rett syndrome, recent work has
      suggested that other tissues also contribute significantly to progression of the
      disease. Indeed, Rett syndrome is known to present with several common peripheral
      pathologies, such as osteopenia, scoliosis, gastrointestinal problems including
      nutritional defects, and general growth deficit. Mouse models assessing the
      potential role of non-neuronal cell types have confirmed both roles in disease
      and potential therapeutic targets. A new picture is emerging in which neurons
      both initiate and drive pathology, while dysfunction of other cell types and
      peripheral tissues exacerbate disease, possibly amplifying further neurologic
      problems, and ultimately result in a positive feedback loop of progressively
      worsening symptoms. Here, we review what is known about neuronal and non-neuronal
      cell types, and discuss how this new, integrative understanding of the disease
      may allow for additional clinical and scientific pathways for treating and
      understanding Rett syndrome.

PMID- 25982837
TI  - In situ coating makes it easier for children to swallow and tolerate tablets and
      capsules.
AB  - AIM: Getting children to swallow tablets and capsules is a challenge, and factors
      that influence their ability to swallow include taste, smell and texture. The aim
      of this study was to explore how well paediatric patients tolerated and accepted
      the MedCoat((r)) in situ coating for tablets and capsules. METHODS: A
      nonrandomised intervention study was performed at the Astrid Lindgren Children's
      Hospital, Karolinska University Hospital, Sweden. We identified 78 paediatric
      patients, 43 females and 35 males, who had problems swallowing tablets and
      capsules and evaluated their abilities with questionnaires. The median age of the
      patients was nine years old, and the range was two to 17 years old. RESULTS:
      Swallowing ability and palatability was improved by in situ coating. The results
      showed that 66 of 77 paediatric patients (86%, 95% confidence interval: 76-93%)
      were able to take the drugs they had been prescribed after in situ coating.
      Swallowing improved in 87% of cases, and palatability improved in 85% of cases.
      CONCLUSION: A study of 77 paediatric patients with a median age of nine years,
      and a range of two to 17 years, found that 86% were able to take the tablets and
      capsules they had been prescribed after they were coated with the MedCoat.

PMID- 25982836
TI  - Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker
      Initiative.
AB  - Despite growing research efforts, no reliable biomarker currently exists for the
      diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are
      urgently needed to improve diagnostic accuracy, prognostic guidance and also to
      serve as efficacy measures or surrogates of target engagement for future clinical
      trials. We here review candidate fluid biomarkers for MSA and provide
      considerations for further developments and harmonization of standard operating
      procedures. A PubMed search was performed until April 24, 2015 to review the
      literature with regard to candidate blood and cerebrospinal fluid (CSF)
      biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for
      eligibility. The final list included 60 studies assessing fluid biomarkers in
      patients with MSA. Most studies have focused on alpha-synuclein, markers of
      axonal degeneration or catecholamines. Their results suggest that combining
      several CSF fluid biomarkers may be more successful than using single markers, at
      least for the diagnosis. Currently, the clinically most useful markers may
      comprise a combination of the light chain of neurofilament (which is consistently
      elevated in MSA compared to controls and Parkinson's disease), metabolites of the
      catecholamine pathway and proteins such as alpha-synuclein, DJ-1 and total-tau.
      Beyond future efforts in biomarker discovery, the harmonization of standard
      operating procedures will be crucial for future success. 

PMID- 25982838
TI  - Meaning creation and employee engagement in home health caregivers.
AB  - The purpose of this study is to contribute to an understanding on how home health
      caregivers experience engagement in their work, and specifically, how aspects of
      home healthcare work create meaning associated with employee engagement. Although
      much research on engagement has been conducted, little has addressed how
      individual differences such as worker orientation influence engagement, or how
      engagement is experienced within a caregiving context. The study is based on a
      qualitative study in two home homecare organisations in Denmark using a think
      aloud data technique, interviews and observations. The analysis suggests
      caregivers experience meaning in three relatively distinct ways, depending on
      their work orientation. Specifically, the nature of engagement varies across
      caregivers oriented towards being 'nurturers', 'professionals', or 'workers', and
      the sources of engagement differ for each of these types of caregivers. The
      article contributes by (i) advancing our theoretical understanding of employee
      engagement by emphasising meaning creation and (ii) identifying factors that
      influence meaning creation and engagement of home health caregivers, which should
      consequently affect the quality of services provided home healthcare patients. 

PMID- 25982835
TI  - Reactive astrocytes and therapeutic potential in focal ischemic stroke.
AB  - Astrocytes are specialized and the most abundant cell type in the central nervous
      system (CNS). They play important roles in the physiology of the brain.
      Astrocytes are also critically involved in many CNS disorders including focal
      ischemic stroke, the leading cause of brain injury and death in patients. One of
      the prominent pathological features of a focal ischemic stroke is reactive
      astrogliosis and glial scar formation. Reactive astrogliosis is accompanied with
      changes in morphology, proliferation, and gene expression in the reactive
      astrocytes. This study provides an overview of the most recent advances in
      astrocytic Ca(2+) signaling, spatial, and temporal dynamics of the morphology and
      proliferation of reactive astrocytes as well as signaling pathways involved in
      the reactive astrogliosis after ischemic stroke based on results from
      experimental studies performed in various animal models. This review also
      discusses the therapeutic potential of reactive astrocytes in focal ischemic
      stroke. As reactive astrocytes exhibit high plasticity, we suggest that
      modulation of local reactive astrocytes is a promising strategy for cell-based
      stroke therapy. 

PMID- 25982839
TI  - Comparable calcium handling of human iPSC-derived cardiomyocytes generated by
      multiple laboratories.
AB  - Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs)
      are being increasingly used to model human heart diseases. hiPSC-CMs generated by
      earlier aggregation-based methods (i.e., embryoid body) often lack functional
      sarcoplasmic reticulum (SR) Ca stores characteristic of mature mammalian CMs.
      Newer monolayer-based cardiac differentiation methods (i.e., Matrigel sandwich or
      small molecule-based differentiation) produce hiPSC-CMs of high purity and yield,
      but their Ca handling has not been comprehensively investigated. Here, we studied
      Ca handling and cytosolic Ca buffering properties of hiPSC-CMs generated
      independently from multiple hiPSC lines at Stanford University, Vanderbilt
      University and University of Wisconsin-Madison. hiPSC-CMs were cryopreserved at
      each university. Frozen aliquots were shipped, recovered from cryopreservation,
      plated at low density and compared 3-5days after plating with acutely-isolated
      adult rabbit and mouse ventricular CMs. Although hiPSC-CM cell volume was
      significantly smaller, cell capacitance to cell volume ratio and cytoplasmic Ca
      buffering were not different from rabbit-CMs. hiPSC-CMs from all three
      laboratories exhibited robust L-type Ca currents, twitch Ca transients and
      caffeine-releasable SR Ca stores comparable to adult CMs. Ca transport by
      sarcoendoplasmic reticulum Ca ATPase (SERCA) and Na/Ca exchanger (NCX) was
      similar in all hiPSC-CM lines, but slower compared to rabbit-CMs. However, the
      relative contribution of SERCA and NCX to Ca transport of hiPSC-CMs was
      comparable to rabbit-CMs. Ca handling maturity of hiPSC-CMs increased from 15 to
      21days post-induction. We conclude that hiPSC-CMs generated independently from
      multiple iPSC lines using monolayer-based methods can be reproducibly recovered
      from cryopreservation and exhibit comparable and functional SR Ca handling. 

PMID- 25982840
TI  - Anatomical organization of the visual dorsal ventricular ridge in the chick
      (Gallus gallus): Layers and columns in the avian pallium.
AB  - The dorsal ventricular ridge (DVR) is one of the main components of the sauropsid
      pallium. In birds, the DVR is formed by an inner region, the nidopallium, and a
      more dorsal region, the mesopallium. The nidopallium contains discrete areas that
      receive auditory, visual, and multisensory collothalamic projections. These
      nidopallial nuclei are known to sustain reciprocal, short-range projections with
      their overlying mesopallial areas. Recent findings on the anatomical organization
      of the auditory DVR have shown that these short-range projections have a columnar
      organization that closely resembles that of the mammalian neocortex. However, it
      is unclear whether this columnar organization generalizes to other areas within
      the DVR. Here we examine in detail the organization of the visual DVR, performing
      small, circumscribed deposits of neuronal tracers as well as intracellular
      fillings in brain slices. We show that the visual DVR is organized in three main
      laminae, the thalamorecipient nucleus entopallium; a dorsally adjacent
      nidopallial lamina, the intermediate nidopallium; and a contiguous portion of the
      ventral mesopallium, the mesopallium ventrale. As in the case of the auditory
      DVR, we found a highly topographically organized system of reciprocal
      interconnections among these layers, which was formed by dorsoventrally oriented,
      discrete columnar bundles of axons. We conclude that the columnar organization
      previously demonstrated in the auditory DVR is not a unique feature but a general
      characteristic of the avian sensory pallium. We discuss these results in the
      context of a comparison between sauropsid and mammalian pallial organization.

PMID- 25982841
TI  - Combined Effect of Ultrasound and Ozone on Bacteria in Water.
AB  - The aim of this study is to assess the synergetic effect of combined ultrasound
      and ozone treatment on the biological disinfection of water on a large-scale
      application using viable plate counts and flow cytometry. Escherichia coli B
      bacteria in saline suspension was treated using a commercially available combined
      ultrasound and ozone system (USO3 (Ultrasonic Systems Gmbh)) for 16 min. Two
      analytical methods were used to assess the results in terms of live and dead
      cells in the bulk liquid: standard viable plate counting recorded in terms of
      colony forming units per milliliter and flow cytometry. In the latter case 1 mL
      of bacterial suspension was stained simultaneously with the fluorescent stains
      SYTO9 and propidium iodide (PI). Transmission electron microscopy was used to
      generate images identifying the biological effects of different treatments using
      ultrasound and ozone on bacterial cell walls. Results demonstrated that treatment
      with ozone alone (1 mg/L) resulted in a significant reduction (93%) in the number
      of live cells after 16 min treatment whereas ultrasound alone showed only a small
      reduction (24%). However, a combination of ozone and ultrasound showed a
      synergistic effect and enhanced the inactivation to 99% after 4 min. A combined
      ultrasound and ozone treatment of bacterial suspensions using a commercial system
      affords a promising method for water disinfection that is better than treatment
      using either method alone. Standard viable plate count analysis is normally used
      to assess the effectiveness of disinfection treatments; however flow cytometry
      proved to be a more sensitive method to determine the actual effects in terms of
      not only live and dead cells but also damaged cells. This type of analysis (cell
      damage) is difficult if not impossible to achieve using traditional plate
      counting methodology.

PMID- 25982842
TI  - Medicago spp. as potential sources of bioactive isoflavones: Characterization
      according to phylogenetic and phenologic factors.
AB  - A high variety of plant species are often proposed as potential natural sources
      of specific bioactive components, with emphasis in phenolic compounds. However,
      the ability to produce a determined phytochemical might be variable, even among
      species with close phylogeny. Furthermore, the metabolic dynamics vary greatly
      according to phenologic factors. Herein, it was verified whether isoflavone
      production in Medicago spp. is more associated with phylogenetic or phenologic
      determinants, to define the optimal productive conditions. Isoflavone profiles
      were characterized in field-grown Medicago species in three phenologic stages.
      Isoflavones were extracted by matrix solid-phase dispersion method and analyzed
      using high-performance liquid chromatography coupled with a diode-array detector.
      The obtained data were evaluated by a generalized linear model (GLM) and linear
      discriminant analysis (LDA). Formononetin, genistein and irilone were the most
      abundant isoflavones, reaching values higher than those present in acknowledged
      plant sources like soy or red clover. Outputs from GLM and LDA indicate that the
      phylogenetic factors are the most defining criteria. This study promotes Medicago
      spp. as potential isoflavone sources, particularly because the effects of these
      compounds are highly dependent on their type and concentration, with potential
      application as foodstuff, feedstuff, or in the nutraceutical and pharmaceutical
      industry. 

PMID- 25982843
TI  - Beneficial effect of the CXCL12-3'A variant for patients undergoing hematopoietic
      stem cell transplantation from unrelated donors.
AB  - The present study aimed to assess the impact of the CXCL12 gene polymorphism
      (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from
      unrelated donors. Toxic complications were less frequent among patients
      transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151,
      p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively).
      Logistic regression analyses confirmed a role of donor A allele (OR=0.509,
      p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition,
      age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was
      independently protective while female to male transplantation and HLA
      compatibility were not significant. The incidence of aGvHD (grades I-IV) was
      lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous
      genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic
      markers with a decreased risk of aGvHD were also seen in multivariate analyses (A
      allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA
      compatibility seemed to play less protective role (p<0.1) while recipient age and
      donor-recipient gender relation were not significant. Moreover, CXCL12-3'-A
      positive patients were less prone to early HHV-6 reactivation (2/34 vs. 19/69,
      p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome
      of unrelated HSCT. 

PMID- 25982844
TI  - Correlation of Interleukin-6 levels and lectins during Schistosoma haematobium
      infection.
AB  - Urogenital schistosomiasis caused by Schistosoma haematobium induces a Th2 immune
      response, including expression of Interleukin-6. IL-6 confers protection from
      experimental Schistosoma-induced pulmonary hypertension and modulates production
      of mannose-binding lectin (MBL) and other lectins. We studied IL-6 levels in
      schistosomiasis and its effect on lectins production. Elevated IL-6 levels
      occurred in cases, compared to controls. IL-6 correlated with the lectins MBL,
      ficolin-2 and Collectin Kidney-1 (CL-K1) in cases, but correlated inversely in
      controls. The study shows that IL-6 levels are elevated in individuals infected
      with urogenital schistosomiasis. IL-6 was also found to be correlated with the
      production of lectins in S. haematobium infection. A similar correlation between
      IL-6 and MBL was observed during visceral leishmaniasis. 

PMID- 25982845
TI  - Calcitonin gene-related peptide cooperates with substance P to inhibit
      melanogenesis and induces apoptosis of B16F10 cells.
AB  - Skin is the largest organ in human body and works as biologically active barrier
      to provide critical preservation of body homeostasis. The skin is highly
      innervated by a plenitude of nerve fiber subpopulations, each carrying one or
      more neuronal mediators. Melanocyte itself also intimately contact with nerve
      fibers to form 'synaptic-like structure' and its functions may be directly
      regulated by the mediators contained in terminals of intra-epidermal nerve
      fibers. Clinical and biochemical studies have suggested that calcitonin gene
      related peptide (CGRP) is involved in vitiligo skin. The present study was
      designed to investigate the effect of CGRP on epidermal melanocytes. After
      treatment with CGRP ranging from 0 to 500 ng/mL for 48 h, tyrosinase activity and
      melanogenesis were with little changes compared to treatment with medium only in
      B16F10 cells. Treatment with 500 ng/mL of CGRP cooperates with substance P (SP)
      (0.1-10 nM) to decrease tyrosinase activity and decrease melanin biosynthesis in
      B16F10 cells in a concentration-dependent manner. Furthermore, CGRP (8-37)
      antagonizes the synergistic effect of CGRP. The effect of CGRP on the cell
      apoptosis was examined. Treatments with 0-500 ng/mL of CGRP for 24 h, the
      expression levels of cleaved caspase-3, total caspase-3, cleaved caspase-9 and
      total caspase-9 were increased in a concentration-dependent manner. And 500 ng/mL
      of CGRP induced B16F10 cell apoptosis showed by TUNEL assay. In addition, Bax
      expression was up-regulated and Bcl-2 down-regulated in response to CGRP
      treatment. Hence, the Bax/Bcl-2 ratio was significantly increased. These in vitro
      observations indicate the pro-apoptotic impact of CGRP on B16F10 cell.

PMID- 25982846
TI  - The betac receptor family - Structural insights and their functional
      implications.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3)
      and IL-5 are members of a small family of cytokines that share a beta receptor
      subunit (betac). These cytokines regulate the growth, differentiation, migration
      and effector function activities of many hematopoietic cells in bone marrow,
      blood and sites of inflammation. Excessive or aberrant signaling can result in
      chronic inflammatory conditions and myeloid leukemias. The crystal structures of
      the GM-CSF ternary complex, the IL-5 binary complex and the very recent IL-3
      receptor alpha subunit build upon decades of structure-function studies, giving
      new insights into cytokine-receptor specificity and signal transduction.
      Selective modulation of receptor function is now a real possibility and the
      structures of the betac receptor family are being used to discover novel and
      disease-specific therapeutics. 

PMID- 25982847
TI  - Successful early postpartum support linked to management, informational, and
      relational continuity.
AB  - OBJECTIVE: to explore ways in which parents experience support from health
      professionals in the early postpartum period and understand how parenting support
      is related to management, informational, and relational continuity. DESIGN: a
      qualitative study consisting of focus group interviews followed by deductive
      content analysis. SETTING AND PARTICIPANTS: a large city in Sweden; 18 women and
      16 men. FINDINGS: study participants reported that parenting support occurs by
      providing consistent advice; indicating who to ask when care questions arise;
      enabling access to the care system when needs surface; providing sufficient
      information about self-management for mother or baby; involving parents in
      discharge planning; distributing information that empowers parents; enabling
      team/clinical care consistency; and appointing persons in the care system who can
      foster parents' feelings of trust--in short: by enabling management,
      informational, and relational continuity. KEY CONCLUSIONS: care continuity
      experiences lead to perceived parenting support in the early postpartum period.
      Effective health care organisations within the postpartum care system must embody
      these types of continuity: management, informational, and relational. There is a
      need for researchers to design tools for measuring continuity and for
      policymakers to enable coherence and co-ordination among professionals.
      IMPLICATIONS FOR PRACTICE: identify parents' needs so that health professionals
      can plan for parents' first few weeks at home and ensure that parents get access
      to appropriate care.

PMID- 25982848
TI  - A critical evaluation of whether recombination in virus-resistant transgenic
      plants will lead to the emergence of novel viral diseases.
AB  - In the evaluation of the potential impacts of first-generation genetically
      modified (GM) crops, one of the most complex issues has been whether the
      expression of viral sequences would lead to the emergence of novel viruses, which
      could occur through recombination between transgene mRNA and that of an infecting
      non-target virus. Here, we examine this issue, focusing on Cucumber mosaic virus
      (CMV), which is a particularly pertinent choice, as it is both a major plant
      pathogen and also the virus with which this question has been studied in the most
      detail. Using recent results on recombination in CMV, we employ a novel framework
      giving particular prominence to the formulation of the risk hypothesis and to
      hypothesis testing via examination of the potential pathway to harm. This allows
      us to conclude with greater certainty that the likelihood of this potential harm,
      the emergence of novel viruses, is low. 

PMID- 25982849
TI  - Self-expandable metal stents versus plastic stents for malignant biliary
      obstruction: a meta-analysis.
AB  - BACKGROUND: Malignant biliary obstruction frequently portends a poor prognosis.
      Palliative treatment with stenting is often required to alleviate symptoms and
      potentially prevent adverse events. OBJECTIVES: The aims of our study were (1) to
      evaluate the clinical difference between self-expandable metal stents (SEMSs) and
      plastic stents (PSs) in both hilar and distal malignant biliary obstruction on
      occlusion rate and 30-day mortality rate (primary outcomes) and stent insertion
      success rate, therapeutic failure, reintervention rate, and adverse events
      (secondary outcomes); (2) to compare unilateral stenting with bilateral stenting
      in hilar malignant obstruction in terms of occlusion rate and 30-day mortality
      rate (primary outcomes) and insertion success rate, therapeutic failure, and
      adverse events (secondary outcomes). METHODS: PubMed, Embase, and Cochrane
      databases were searched for studies that provided data about malignant biliary
      obstruction and stent therapy. We included randomized, controlled trials (RCT),
      prospective observational cohort, and retrospective case-control studies. The
      quality of each included RCT study was assessed by the Jadad scale. Mantel
      Haenszel odds ratios (ORs) and mean differences were calculated by using a random
      effects model. RESULTS: Nineteen studies involving 1989 patients (1045 SEMSs and
      944 PSs) were included for the comparison of SEMSs and PSs. We also included 7
      studies that compared unilateral with bilateral stenting involving 634 patients
      (346 unilateral and 268 bilateral). Our meta-analysis confirmed that SEMSs are
      associated with a statistically significant lower risk of occlusion compared with
      PSs in the short term (OR 0.27; 95% confidence interval [CI], 0.13-0.60) and long
      term (OR 0.38; 95% CI, 0.28-0.53). SEMSs had a lower 30-day occlusion rate than
      PSs in both hilar malignant obstruction (OR 0.16; 95% CI, 0.04-0.62) and distal
      malignant obstruction (OR 0.36; 95% CI, 0.14-0.93). SEMSs had a lower long-term
      occlusion rate compared with PSs in hilar malignant obstruction (OR 0.28; 95% CI,
      0.19-0.39) and distal malignant obstruction (OR 0.42; 95% CI, 0.27-0.64). The 30
      day mortality rate was similar with SEMSs and PSs (OR 0.74; 95% CI, 0.47-1.17).
      Therapeutic failure was more likely when using PSs (13%) compared with SEMSs (7%)
      (OR 0.43; 95% CI, 0.27-0.67). SEMSs required fewer reinterventions compared with
      PSs (mean difference, -0.49; 95% CI, -0.8 to -0.19). The incidence of cholangitis
      was statistically lower with SEMSs (8% vs 21%) (OR 0.41; 95% CI, 0.22-0.76).
      Bilateral stenting for hilar obstruction was not associated with a lower
      obstruction rate than unilateral stenting (OR 1.49; 95% CI, 0.77-2.89) or a lower
      30-day mortality rate (OR 0.73; 95% CI, 0.29-1.79). There was no statistical
      difference in therapeutic failure (OR 1.47; 95% CI, 0.77-2.89) or cholangitis
      incidence (OR 0.61; 95% CI, 0.27-1.38). CONCLUSION: SEMSs are associated with a
      statistically significantly lower occlusion rate, less therapeutic failure, less
      need for reintervention, and lower cholangitis incidence. There was no
      statistically significant difference in occlusion rate, therapeutic failure, and
      cholangitis incidence with bilateral stenting. Guideline recommendations may need
      to be modified to reflect clear and compelling data demonstrating the benefit of
      SEMSs in patients with malignant biliary obstruction. Bilateral stenting should
      be avoided because it has no benefit over unilateral stenting in terms of
      occlusion rate or therapeutic failure.

PMID- 25982850
TI  - Alloyed ZnS-CuInS2 Semiconductor Nanorods and Their Nanoscale Heterostructures
      for Visible-Light-Driven Photocatalytic Hydrogen Generation.
AB  - A promising photocatalytic system in the form of heterostructured nanocrystals
      (HNCs) is presented wherein alloyed ZnS-CuInS2 (ZCIS) semiconductor nanorods are
      decorated with Pt and Pd4 S nanoparticles. This is apparently the first report on
      the colloidal preparation and photocatalytic behavior of ZCIS-Pt and ZCIS-Pd4 S
      nanoscale heterostructures. Incorporation of Pt and Pd4 S cocatalysts leads to
      considerable enhancement of the photocatalytic activity of ZCIS for visible-light
      driven hydrogen production. 

PMID- 25982851
TI  - A control system analysis of the dynamic response of N-methyl-D-aspartate
      glutamate receptors to alcoholism and alcohol withdrawal.
AB  - BACKGROUND: N-methyl-D-Aspartate (NMDA) and its receptors (NMDAR) play a critical
      role in glutamatergic neurotransmission. Ethanol molecules inhibit these
      receptors, and if the brain is exposed to ethanol chronically, NMDA-induced
      glutamatergic changes can result in physical dependence to ethanol in order to
      sustain normal brain function. In these cases, removal of ethanol from the system
      results in excitotoxic withdrawal. One compensatory mechanism the brain uses to
      regulate extracellular glutamate concentration is modulating the number of NMDARs
      at the synapse. Previous work has shown that the number of functional NMDARs at
      the synapse can be changed by three mechanisms: additional receptors can be
      synthesized and inserted, receptors can be recruited to the synapse from
      extrasynaptic regions, or the functionality of existing receptors can be
      modified. METHODS: In this study, we consider the dynamic relocation control of
      NMDARs in response to chronic alcoholism and withdrawal. Specifically, we (1)
      propose and construct a mathematical model of the relocation control as a
      negative feedback system with an explicit set point, (2) investigate the effect
      of various ethanol consumption and withdrawal profiles on the NMDAR population,
      and (3) propose and calculate quantitative measures for the extent of withdrawal
      based on modeled NMDAR populations. RESULTS: A relocation-only model with an
      explicit set point was developed. The model was shown to apply across a wide
      range of controller parameters. The results suggest that withdrawal severity does
      not depend upon the dynamics involved in the development of dependence, and that
      regulating the blood alcohol level throughout the progression of withdrawal can
      minimize excitotoxic withdrawal symptoms. CONCLUSIONS: The negative feedback
      control system produced characteristic behaviors of NMDAR populations in response
      to simulations of alcohol dependence and abrupt withdrawal. The model can also
      predict the severity of excitotoxic withdrawal following various alcohol
      consumption and/or withdrawal patterns in order to generate testable hypotheses
      regarding ameliorating withdrawal.

PMID- 25982852
TI  - The Danish fat tax-Effects on consumption patterns and risk of ischaemic heart
      disease.
AB  - OBJECTIVE: To examine the effects on consumption and risk of ischemic heart
      disease (IHD) of the Danish fat tax, effective from October 2011 to January 2013.
      METHODS: We used comprehensive retail outlet data on the sale of twelve foodstuff
      categories targeted by the fat tax. Data covered January 2010 to July 2013. IHD
      risk was assessed by modelling first the effect of changes in intake of
      monounsaturated, polyunsaturated and saturated fat and dietary cholesterol on
      serum cholesterol and subsequently modelling the resulting changes in risk of IHD
      using two different methods. RESULTS: The total sale of the included foodstuffs
      decreased by 0.9%. The fat tax was associated with marginal changes in population
      risk of IHD. One estimate suggests an increased population risk of IHD by 0.2%
      and the other estimate suggests that the risk of IHD decreased by 0.3%.
      CONCLUSIONS: The Danish fat tax had a marginal effect on population consumption
      of fat and risk of IHD. Fat taxes have to be carefully designed to prevent
      possible adverse effects from outweighing its beneficial effects on health
      outcomes. Policymakers must therefore be more ambitious in relation to food
      taxes, e.g. by implementing more comprehensive tax-subsidy schemes.

PMID- 25982853
TI  - ProtDCal: A program to compute general-purpose-numerical descriptors for
      sequences and 3D-structures of proteins.
AB  - BACKGROUND: The exponential growth of protein structural and sequence databases
      is enabling multifaceted approaches to understanding the long sought sequence
      structure-function relationship. Advances in computation now make it possible to
      apply well-established data mining and pattern recognition techniques to these
      data to learn models that effectively relate structure and function. However,
      extracting meaningful numerical descriptors of protein sequence and structure is
      a key issue that requires an efficient and widely available solution. RESULTS: We
      here introduce ProtDCal, a new computational software suite capable of generating
      tens of thousands of features considering both sequence-based and 3D-structural
      descriptors. We demonstrate, by means of principle component analysis and Shannon
      entropy tests, how ProtDCal's sequence-based descriptors provide new and more
      relevant information not encoded by currently available servers for sequence
      based protein feature generation. The wide diversity of the 3D-structure-based
      features generated by ProtDCal is shown to provide additional complementary
      information and effectively completes its general protein encoding capability. As
      demonstration of the utility of ProtDCal's features, prediction models of N
      linked glycosylation sites are trained and evaluated. Classification performance
      compares favourably with that of contemporary predictors of N-linked
      glycosylation sites, in spite of not using domain-specific features as input
      information. CONCLUSIONS: ProtDCal provides a friendly and cross-platform
      graphical user interface, developed in the Java programming language and is
      freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . ProtDCal
      introduces local and group-based encoding which enhances the diversity of the
      information captured by the computed features. Furthermore, we have shown that
      adding structure-based descriptors contributes non-redundant additional
      information to the features-based characterization of polypeptide systems. This
      software is intended to provide a useful tool for general-purpose encoding of
      protein sequences and structures for applications is protein classification,
      similarity analyses and function prediction.

PMID- 25982854
TI  - TELELAP ALF-X Robotic-assisted Laparoscopic Hysterectomy: Feasibility and
      Perioperative Outcomes.
AB  - STUDY OBJECTIVE: To show the safety, feasibility, and perioperative outcomes of
      total TELELAP ALF-X hysterectomy (SOFAR S.p.A., ALF-X Surgical Robotics
      Department, Trezzano Rosa, Milan, Italy). DESIGN: Phase II study (Canadian Task
      Force II-2). SETTING: Catholic University of the Sacred Heart, Rome, Italy.
      PATIENTS: From October 2013 to May 2014, 80 women underwent total TELELAP ALF-X
      hysterectomy. The study population was divided into 2 groups according to
      surgical procedures: total hysterectomy +/- bilateral salpingo-oophorectomy
      (group 1) and endometrial cancer patients staged with pelvic lymphadenectomy
      (group 2). INTERVENTIONS: Total TELELAP ALF-X hysterectomy +/- bilateral salpingo
      oophorectomy with or without pelvic lymphadenectomy. MEASUREMENTS AND MAIN
      RESULTS: The median age was 51 years (range, 48-79), and the median body mass
      index was 24 kg/m(2) (range, 17.3-34.2). Forty-five patients (56.2%) had previous
      surgery. The median operative time was 140 minutes (range, 58-320) in group 1 and
      197 minutes (range, 129-290) in group 2 (p < .001). The median docking time was 8
      minutes (range, 3-25). During the study period, a significant trend in operative
      time reduction was observed. Procedures were successfully performed without
      conversion in 93.7% of cases. We observed 2 (2.5%) intraoperative complications,
      3 (3.7%) conversions to standard laparoscopy, and 2 (2.5%) to laparotomy. The
      median time to discharge was 2 days (range, 1-5). One patient (1.2%) was
      readmitted in the early postoperative period. CONCLUSION: As new technology
      evolves, critical appraisal of patient-related outcomes, use, cost, and access to
      minimally invasive hysterectomy must remain a priority. Despite the relative
      small number of our series, we showed the feasibility and safety of total TELELAP
      ALF-X hysterectomy for benign and malignant disease.

PMID- 25982855
TI  - Phosphohistone-H3 (PHH3) is prognostic relevant in Merkel cell carcinomas but
      Merkel cell polyomavirus is a more powerful prognostic factor than AJCC clinical
      stage, PHH3, Ki-67 or mitotic indices.
AB  - Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV)
      have better prognosis than those without MCPyV. The relationship between mitotic
      index (MI) and MCC outcome has remained elusive because of the difficulty in
      differentiating mitotic cells from apoptotic ones. We evaluated the role of
      phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV
      positive or -negative MCC patients, and assessed its prognostic value in
      comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE)
      staining. We compared the prognostic value of PHH3 mitotic index with that of MI
      by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive
      immunoreactivity was mostly observed in mitotic figures. Multivariate analysis
      significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the
      American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51)
      were observed as significantly independent prognostic factors for OS. PHH3
      positive cell counts/10 HPF was a slightly significant independent prognostic
      factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in
      MCC patients are useful in prognostication, although MCPyV-infection is a more
      powerful prognostic factor in MCCs than the AJCC scheme on proliferation or
      mitotic indices. 

PMID- 25982856
TI  - Curative endoscopic submucosal dissection of large nonpolypoid superficial
      neoplasms in ulcerative colitis (with videos).
AB  - BACKGROUND: Endoscopic resection of superficial neoplasms in inflammatory bowel
      disease (IBD) is appropriate if a complete resection can be achieved. However,
      EMR is ineffective for large, nonpolypoid neoplasms in IBD due to submucosal
      fibrosis, and no data are available on the efficacy of endoscopic submucosal
      dissection (ESD). OBJECTIVE: To assess ESD feasibility and efficacy for large,
      nonpolypoid neoplasms in patients with IBD. DESIGN: Prospective case series.
      SETTING: Multicenter: Italian and Japanese centers. PATIENTS: Consecutive
      patients with long-standing ulcerative colitis and a superficial nonpolypoid
      neoplasm, >20 mm within the colitic mucosa. INTERVENTION: Neoplasm
      characterization and delineation by chromoscopy and narrow-band imaging. ESD
      performed according to the standard technique. MAIN OUTCOME MEASUREMENTS:
      Feasibility, safety, curative resection rates. RESULTS: Nine patients with 10
      neoplasms were included (7 and 3 in the Italian and Japanese centers,
      respectively). Neoplasms were laterally spreading tumors-non-granular in 5 cases,
      in the left side of the colon in 7, had median size of 33 mm, and were associated
      with scar in 5 cases. Margin delineation was difficult in 5 cases. Submucosal
      fibrosis was present in 9 cases. ESD was en bloc with negative margins (R0) in 8
      cases, and curative in 7. No endoscopic invisible dysplasia or cancer was found
      during the follow-up (median 24 months, range 6-72 months) at the resection site
      and elsewhere within the colitic mucosa. LIMITATIONS: Small series. CONCLUSION:
      ESD achieves curative resections in patients with IBD, but the procedure is
      difficult because of the high prevalence of submucosal fibrosis. Patients need to
      be accurately evaluated before resection and adhere to strict long-term follow
      ups.

PMID- 25982857
TI  - Brain structural alterations associated with young women with subthreshold
      depression.
AB  - Neuroanatomical abnormalities in patients with major depression disorder (MDD)
      have been attracted great research attention. However, the structural alterations
      associated with subthreshold depression (StD) remain unclear and, therefore,
      require further investigation. In this study, 42 young women with StD, and 30
      matched non-depressed controls (NCs) were identified based on two-time Beck
      Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region
      of interest method were used to investigate altered gray matter volume (GMV) and
      white matter volume (WMV) among a non-clinical sample of young women with StD.
      VBM results indicated that young women with StD showed significantly decreased
      GMV in the right inferior parietal lobule than NCs; increased GMV in the
      amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the
      posterior cingulate cortex and precuneus. Together, structural alterations in
      specific brain regions, which are known to be involved in the fronto-limbic
      circuits implicated in depression may precede the occurrence of depressive
      episodes and influence the development of MDD. 

PMID- 25982858
TI  - The relationship between TNF alpha gene polymorphisms (-238/-308), TNF RII VNTR
      (p75) and outcomes of hepatitis B virus infection in Tunisian population.
AB  - The present study was undertaken to investigate the association between Hepatitis
      B Virus (HBV) infection and polymorphisms of tumour necrosis factor alpha TNF
      alpha -308 G>A, TNF-alpha -238 G>A and TNF RII VNTR (p75) gene promoter in a
      Tunisian population. Blood samples were collected from 100 Tunisian patients with
      HBV infection, 45 with Chronic Hepatitis (CH), 36 with Liver Cirrhosis (LC), 15
      with Hepatocellular Carcinoma (HCC) and 200 healthy individuals of similar
      ethnicity. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping
      of the analysed polymorphisms was performed using Amplified Refractory Mutation
      System-Polymerase Chain Reaction (ARMS-PCR), Restriction Fragment Length
      Polymorphism (RFLP) and Variable Number Tandem Repeat PCR (PCR-VNTR). The variant
      homozygotes -308 GG were associated with 50% decreased risk of HBV chronic
      infection (GG vs AA+GA; p=0.010; OR=0.50; 95%CI=0.29-0.85). However, the carriers
      of minor allele -308 A have higher risk (1.5 times) to develop a chronic
      infection than other patients (p=0.027; OR=1.46; 95%CI=1.04-2.06). The minor
      allele of -238 polymorphism was positively associated with virus resistance and
      the development of chronic infection (p=0.043; OR=1.42; 95%CI =1.01 1.99). The
      distribution of -308, -238 and TNF RII VNTR (p75) among the three groups differed
      significantly. For HCC groups, there were statistically significant differences
      in allele distribution in -308, -238 respectively in which A allele remains a
      risk factor for HBV evolution to HCC (p=0.008 and p=0.026). Haplotype analysis
      revealed that TNF-alpha (-308A; -238A) was significantly associated to HBV
      chronic infection and moreover to disease aggravation to HCC stage. Our findings
      imply that variations in the genes governing the levels of constitutive and
      inducible TNF-alpha and TNF RII might be an important risk factor, which could
      explain the variable outcomes of HBV infection. 

PMID- 25982859
TI  - Transcription factor hlh-2/E/Daughterless drives expression of alpha integrin ina
      1 during DTC migration in C. elegans.
AB  - Integrins are involved in a vast number of cell behaviors due to their roles in
      adhesion and signaling. The regulation of integrin expression is of particular
      interest as a mechanism to drive developmental events and for the role of altered
      integrin expression profiles in cancer. Dynamic regulation of the expression of
      integrin receptors is required for the migration of the distal tip cell (DTC)
      during gonadogenesis in Caenorhabditis elegans. alpha integrin ina-1 is required
      for DTC motility, yet is up-regulated by an unknown mechanism. Analysis of the
      promoter for alpha integrin ina-1 identified two E-box sequences that are
      required for ina-1 expression in the DTC. Knockdown of transcription factor hlh
      2, an established E-box binding partner and ortholog of E/Daughterless, prevented
      expression of a transcriptional fusion of the ina-1 promoter to RFP and blocked
      DTC migration. Similarly, knockdown of hlh-2 also prevented expression of a
      translational fusion of the genomic ina-1 gene to GFP while blocking DTC
      migration. Knockdown of HLH-2 binding partner MIG-24 also reduced ina-1
      expression and DTC migration. Overall, these results show that the transcription
      factor hlh-2 is required for up-regulation of ina-1 at the onset of DTC
      migration. 

PMID- 25982861
TI  - Spectrum of mutations in the ATP binding domain of ATP7B gene of Wilson Disease
      in a regional Indian cohort.
AB  - Wilson disease is an autosomal recessive disorder of abnormal copper accumulation
      in the liver, brain, kidney and cornea, resulting in hepatic and neurological
      abnormalities, which results from impaired ATP7B protein function due to
      mutations in candidate ATP7B gene, till date more than 500 disease causing
      mutations were found. In India most disease causing mutations were identified in
      ATP-BD. DNA samples of the 101 WD cases and 100 control population were analyzed
      for mutations. 11 mutations were identified in 57 chromosomes. Three novel
      mutations, c.3310T>A (p.Cys1104Ser), c.3337C>A (p.Leu1113Met) on exon 15 and
      c.3877G>A (p.Glu1293Lys) on exon 18 were identified for the first time in the
      ATP7B gene. Two mutations, c.3121C>T (p.Arg1041Trp) and c.3128T>C (p.Leu1043Pro)
      on exon 14 were discovered for the first time in Indian Wilson disease patients.
      Four previously reported mutations c.3008C>T, c.3029A>G on exon 13, c.3182G>A on
      exon 14 and c.3809A>G on exon 18 from South India were also found in this study.
      Our research has enriched the spectrum of mutations of the ATP7B gene in the
      south Indian population. The detection of new mutations in the ATP7B gene can aid
      in genetic counseling and clinical or/prenatal diagnosis.

PMID- 25982862
TI  - The Ty1-copia LTR retroelement family PARTC is highly conserved in conifers over
      200 MY of evolution.
AB  - Long Terminal Repeat retroelements (LTR-RTs) are a major component of many plant
      genomes. Although well studied and described in angiosperms, their features and
      dynamics are poorly understood in gymnosperms. Representative complete copies of
      a Ty1-copia element isolate in Picea abies and named PARTC were identified in six
      other conifer species (Picea glauca, Pinus sylvestris, Pinus taeda, Abies
      sibirica, Taxus baccata and Juniperus communis) covering more than 200 million
      years of evolution. Here we characterized the structure of this element, assessed
      its abundance across conifers, studied the modes and timing of its amplification,
      and evaluated the degree of conservation of its extant copies at nucleotide level
      over distant species. We demonstrated that the element is ancient, abundant,
      widespread and its paralogous copies are present in the genera Picea, Pinus and
      Abies as an LTR-RT family. The amplification leading to the extant copies of
      PARTC occurred over long evolutionary times spanning 10s of MY and mostly took
      place after the speciation of the conifers analyzed. The level of conservation of
      PARTC is striking and may be explained by low substitution rates and limited
      removal mechanisms for LTR-RTs. These PARTC features and dynamics are
      representative of a more general scenario for LTR-RTs in gymnosperms quite
      different from that characterizing the vast majority of LTR-RT elements in
      angiosperms. 

PMID- 25982860
TI  - IFNA2: The prototypic human alpha interferon.
AB  - The human interferon alpha2 (IFNalpha2) was the first highly active IFN subtype
      to be cloned in the early eighties. It was also the first IFN and the first
      cytokine to be produced and commercialized by the pharmaceutical industry. Ipso
      facto it became the favorite IFNalpha subtype for academic researchers. For this
      fortunate reason IFNalpha2 has been at the origin of most discoveries related to
      the mechanism of action of type I interferons. 

PMID- 25982863
TI  - The MTNR1B gene polymorphism rs10830963 is associated with gestational diabetes
      in a Brazilian population.

PMID- 25982864
TI  - [Item 237 - UE 8 Acrosyndromes (Raynaud's phenomenon, erythermalgia,
      acrocyanosis, frostbite, digital ischemia)].

PMID- 25982867
TI  - A systematic approach to implementing and evaluating clinical guidelines: The
      results of fifteen years of Preventive Child Health Care guidelines in the
      Netherlands.
AB  - Preventive Child Health Care (PCHC) services are delivered to all children in the
      Netherlands by approximately 5500 doctors, nurses and doctor's assistants. In
      1996, The Dutch Ministry of Health, Welfare and Sports asked for the development
      of evidence-based PCHC guidelines. Since 1998, twenty-five guidelines have been
      published. Levels of implementation affect outcomes and so implementation and
      evaluation of the actual use of guidelines are essential. At the outset, there
      was a national implementation plan with six main activities: a) determinant
      analysis before the implementation of a guideline, b) innovation strategies
      tailored to the determinants, c) dissemination to all professionals, d) ongoing
      evaluation of the awareness and use of the guidelines, e) trained implementation
      coordinator(s) in each PCHC organization and f) a national help desk. The
      awareness and use of the guidelines in random samples of doctors, nurses and
      doctor's assistants were surveyed using questionnaires. The respondents stated
      (on a 7-point scale) the proportion of all children they had exposed to given
      core elements in a guideline. The aim is for at least 90% of the professionals to
      be aware of the guideline and for 80% to perform the core elements for all (or
      nearly all) children. The six main activities, with the exception of ongoing
      evaluation, were gradually put into place, albeit only gradually, between 1998
      and 2015 for all guidelines. In 2012, the use of individual core elements in all
      guidelines, dating from before 2012, varied from 28% to 100%. One guideline met
      both criteria of 90% awareness and 80% use, and three guidelines nearly met these
      criteria. Looking back on fifteen years of PCHC guidelines, we may conclude that
      the guidelines produced recently are implemented in accordance with the national
      implementation plan. Unfortunately, the evaluation of guideline use continues to
      be a difficulty. 

PMID- 25982865
TI  - [Item 299 - UE 9 Epithelial skin tumors and melanoma].

PMID- 25982868
TI  - The effect of a severe health shock on work behavior: Evidence from different
      health care regimes.
AB  - In this paper, we use the policy variation of two different types of health
      insurance in the US and in Denmark - employer-provided and universal insurance
      combined with substantial differences in expected and actual medical out-of
      pocket expenditures - to explore the effect of new severe health shocks on the
      labor force participation of older workers. Our results not only provide insight
      into how relative disease risk affects labor force participation at older ages,
      but also into how different types of health care and health insurance systems
      affect individual decisions of labor force participation. Although employer-tied
      health insurance and greater out-of-pocket medical expenditures give US Americans
      greater incentives to continue to work, we find only small differences in the
      work response between the two countries. We provide compelling evidence that our
      somewhat counterintuitive finding is the result of differential mortality and
      baseline health differences coupled with distinct treatment regimes under the
      respective health care systems. 

PMID- 25982866
TI  - [Ulceration or erosion of the oral and/or genital mucosa].

PMID- 25982869
TI  - Globalization, democracy, and child health in developing countries.
AB  - Good health is crucial for human and economic development. In particular poor
      health in childhood is of utmost concern since it causes irreversible damage and
      has implications later in life. Recent research suggests globalization is a
      strong force affecting adult and child health outcomes. Yet, there is much
      unexplained variation with respect to the globalization effect on child health,
      in particular in low- and middle-income countries. One factor that could explain
      such variation across countries is the quality of democracy. Using panel data for
      70 developing countries between 1970 and 2009 this paper disentangles the
      relationship between globalization, democracy, and child health. Specifically the
      paper examines how globalization and a country's democratic status and historical
      experience with democracy, respectively, affect infant mortality. In line with
      previous research, results suggest that globalization reduces infant mortality
      and that the level of democracy in a country generally improves child health
      outcomes. Additionally, democracy matters for the size of the globalization
      effect on child health. If for example Cote d'Ivoire had been a democracy in the
      2000-2009 period, this effect would translate into 1200 fewer infant deaths in an
      average year compared to the situation without democracy. We also find that
      nutrition is the most important mediator in the relationship. To conclude,
      globalization and democracy together associate with better child health in
      developing countries. 

PMID- 25982870
TI  - Potential sexual transmission of Trypanosoma cruzi in mice.
AB  - Infection with the protozoan parasite Trypanosoma cruzi, the etiologic agent of
      human Chagas disease, results in life-long infection. Infective trypomastigotes
      circulate in the bloodstream and have the capacity to infect any cell type,
      including reproductive tissue. This study sought to assess the potential for
      sexual transmission of T. cruzi in an experimental mouse model. The conditions
      used in this study, in which acutely infected males and immunosuppressing the
      females, created a worst-case scenario allowing for the greatest chance of
      measuring transmission through intercourse. Male BALB/c mice were infected and
      mated with uninfected females, and the females were subsequently examined for T.
      cruzi tissue parasitism. A single transmission event of 61 total matings was
      observed, indicating a low but non-zero risk potential for male-to-female sexual
      transmission of T. cruzi. 

PMID- 25982871
TI  - Cost analysis of long-term outcomes of an urban mental health court.
AB  - Multiple studies have demonstrated decreased recidivism and increased treatment
      engagement for individuals with serious mental illness involved in Mental Health
      Courts (MHC). However, the limited availability of social and fiscal resources
      requires an analysis of the relationship between a program's effectiveness and
      its costs. Outcome costs associated with a sample of 105 participants discharged
      for more than 1 year - and grouped by completion status - were compared to an
      eligible sample not enrolled (n=45). Transactional costs analysis (TCA) was used
      to calculate outcomes associated with treatment, arrest, and confinement in the
      12-month post-MHC. Total outcome costs for the Successful Group ($16,964)
      significantly differed from the Unsuccessful ($32,258) and Compare Groups
      ($39,870). Costs associated with the higher number of arrests for those in the
      Compare Group created the largest differences. Total cost savings between
      Successful and Compare (M=$22,906) equated to $916,240 and savings between
      Unsuccessful and Compare (M=$7612) were $494,708. The total combined cost savings
      for participants in the 12-month post-MHC period was $1,411,020. While it is
      important to understand that MHCs and the individuals that they serve vary and
      these results are for a felony-level court, policy makers and researchers can use
      these results to guide their decision-making. 

PMID- 25982872
TI  - Artificial collagen-filament scaffold promotes axon regeneration and long tract
      reconstruction in a rat model of spinal cord transection.
AB  - Traumatically injured spinal cord (SC) displays structural damage that includes
      discontinuity of long tracts and cavitations. Axonal regrowth beyond the lesion
      is necessary to achieve functional recovery following SC injury. We report here
      the development of an artificial collagen-filament (CF) scaffold to replace the
      SC in 8-week-old female Fisher rats. Axonal sprouting and regrowth was very rapid
      following grafting of the CF. One week after implantation, the scaffold was
      filled with cells of host origin and with regenerated axons. Histological
      examination of SC adjacent to the scaffold showed little cavity formation or
      fibrous scarring. Eight weeks after implantation, myelinated nerve fibers were
      found in the scaffold and 10-25 % of rubrospinal tracts were repaired. Four to
      six weeks after transplantation, motor evoked potentials were recorded in CF
      grafted rats but were not detectable in non-grafted rats. Electrophysiological
      and histological examinations revealed the grafted CF was likely to function as a
      nerve tract. In addition, these results suggest that collagen fibers may provide
      a permissive microenvironment for the elongation of SC axons and to support the
      process of spinal cord regeneration. 

PMID- 25982873
TI  - Genomic heterogeneity in multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable malignancy in majority of patients
      characterized by clonal proliferation of plasma cells. To date, treatment is
      established based on general conditions and age of patients. However, MM is a
      heterogeneous disease, featured by various subtypes and different outcomes. Thus,
      the understanding of MM biology is currently a major challenge to eventually cure
      the disease. During the last decade, karyotype studies and gene expression
      profiling have identified robust prognostic markers as well as a widespread
      genomic landscape. More recently, studies of epigenetic, transcriptional
      modifications and next generation sequencing have allowed characterization of
      critical genes and pathways, clonal heterogeneity and mutational profiles
      involved in myelomagenesis. Altogether, these findings constitute important tools
      to develop new targeted and personalized therapies in MM.

PMID- 25982874
TI  - An automated transition state search using classical trajectories initialized at
      multiple minima.
AB  - Very recently, we proposed an automated method for finding transition states of
      chemical reactions using dynamics simulations; the method has been termed
      Transition State Search using Chemical Dynamics Simulations (TSSCDS) (E. Martinez
      Nunez, J. Comput. Chem., 2015, 36, 222-234). In the present work, an improved
      automated search procedure is developed, which consists of iteratively running
      different ensembles of trajectories initialized at different minima. The
      iterative TSSCDS method is applied to the complex C3H4O system, obtaining a total
      of 66 different minima and 276 transition states. With the obtained transition
      states and paths, statistical RRKM calculations and Kinetic Monte Carlo
      simulations are carried out to study the fragmentation dynamics of propenal,
      which is the global minimum of the system. The kinetic simulations provide a
      (three-body dissociation)/(CO elimination) ratio of 1.49 for an excitation energy
      of 148 kcal mol(-1), which agrees well with the corresponding value obtained in
      the photolysis of propenal at 193 nm (1.1), suggesting that at least these two
      channels: three-body dissociation (to give H2 + CO + C2H2) and CO elimination
      occur on the ground electronic state. 

PMID- 25982875
TI  - Positional obstructive sleep apnea in bariatric surgery patients: risk factor for
      postoperative cardiopulmonary complications?
AB  - BACKGROUND: Up to 80 % of the bariatric surgery (BS) patients suffer from
      obstructive sleep apnea (OSA). BS patients with moderate to severe OSA (apnea
      hypopnea index (AHI) >=15) are usually treated with continuous positive airway
      pressure (CPAP). This is not indicated in mild OSA patients (AHI <15). However,
      >50 % of patients with mild OSA have positional OSA (POSA); their AHI is at least
      twice as high in supine sleeping position than in other positions. Since many
      patients sleep in supine position for surgical safety reasons after BS,
      evaluating the AHI in this position might be more relevant in this group. The aim
      of this study is to evaluate the postoperative cardiopulmonary complication rate
      in mild OSA patients with and without POSA. Secondary aim is to evaluate
      predictive factors for POSA. METHODS: A single-institute retrospective analysis
      was achieved with all consecutive patients who underwent primary laparoscopic
      Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy between 2006 and
      2014. All patients with an AHI between 5 and 15 were included. Postoperative
      complications were compared between POSA and non-POSA patients. Predictive
      factors were evaluated through univariate and multivariable logistic regression
      analysis. RESULTS: A total of 277 patients, 153 with and 124 without POSA, were
      included. After BS, three patients (1.1 %) experienced severe cardiopulmonary
      complications. No significant difference was found between POSA and non-POSA
      patients. In multivariate analysis, age and BMI were found to be negative
      predictors for POSA. CONCLUSION: In terms of 30-day postoperative cardiopulmonary
      outcome, CPAP therapy is not indicated in mild (P)OSA patients scheduled for BS.

PMID- 25982876
TI  - Wastewater treatment in the pulp-and-paper industry: A review of treatment
      processes and the associated greenhouse gas emission.
AB  - Pulp-and-paper mills produce various types of contaminants and a significant
      amount of wastewater depending on the type of processes used in the plant. Since
      the generated wastewaters can be potentially polluting and very dangerous, they
      should be treated in wastewater treatment plants before being released to the
      environment. This paper reviews different wastewater treatment processes used in
      the pulp-and-paper industry and compares them with respect to their contaminant
      removal efficiencies and the extent of greenhouse gas (GHG) emission. It also
      evaluates the impact of operating parameters on the performance of different
      treatment processes. Two mathematical models were used to estimate GHG emission
      in common biological treatment processes used in the pulp-and-paper industry.
      Nutrient removal processes and sludge treatment are discussed and their
      associated GHG emissions are calculated. Although both aerobic and anaerobic
      biological processes are appropriate for wastewater treatment, their combination
      known as hybrid processes showed a better contaminant removal capacity at higher
      efficiencies under optimized operating conditions with reduced GHG emission and
      energy costs. 

PMID- 25982877
TI  - Factors Affecting Dimensional Accuracy of 3-D Printed Anatomical Structures
      Derived from CT Data.
AB  - Additive manufacturing and bio-printing, with the potential for direct
      fabrication of complex patient-specific anatomies derived from medical scan data,
      are having an ever-increasing impact on the practice of medicine. Anatomic
      structures are typically derived from CT or MRI scans, and there are multiple
      steps in the model derivation process that influence the geometric accuracy of
      the printed constructs. In this work, we compare the dimensional accuracy of 3-D
      printed constructs of an L1 vertebra derived from CT data for an ex vivo cadaver
      T-L spine with the original vertebra. Processing of segmented structures using
      binary median filters and various surface extraction algorithms is evaluated for
      the effect on model dimensions. We investigate the effects of changing CT
      reconstruction kernels by scanning simple geometric objects and measuring the
      impact on the derived model dimensions. We also investigate if there are
      significant differences between physical and virtual model measurements. The 3-D
      models were printed using a commercial 3-D printer, the Replicator 2 (MakerBot,
      Brooklyn, NY) using polylactic acid (PLA) filament. We found that changing
      parameters during the scan reconstruction, segmentation, filtering, and surface
      extraction steps will have an effect on the dimensions of the final model. These
      effects need to be quantified for specific situations that rely on the accuracy
      of 3-D printed models used in medicine or tissue engineering applications. 

PMID- 25982878
TI  - Multi-channel EEG signal feature extraction and pattern recognition on horizontal
      mental imagination task of 1-D cursor movement for brain computer interface.
AB  - Brain computer interfaces (BCIs), based on multi-channel electroencephalogram
      (EEG) signal processing convert brain signal activities to machine control
      commands. It provides new communication way with a computer by extracting
      electroencephalographic activity. This paper, deals with feature extraction and
      classification of horizontal mental task pattern on 1-D cursor movement from EEG
      signals. The hemispherical power changes are computed and compared on alpha &
      beta frequencies and horizontal cursor control extracted with only mental
      imagination of cursor movements. In the first stage, features are extracted with
      the well-known average signal power or power difference (alpha and beta) method.
      Principal component analysis is used for reducing feature dimensions. All
      features are classified and the mental task patterns are recognized by three
      neural network classifiers which learning vector quantization, multilayer neural
      network and probabilistic neural network due to obtaining acceptable good results
      and using successfully in pattern recognition via k-fold cross validation
      technique. 

PMID- 25982879
TI  - Approaching atrial septal defects in pulmonary hypertension.
AB  - Atrial septal defects (ASDs) are one of the most frequent congenital cardiac
      malformations, accounting for about 8-10% of all congenital heart defects. The
      prevalence of pulmonary arterial hypertension (PAH) in adults with an ASD is 8
      10%. Different clinical PAH scenarios can be encountered. At one end of the
      spectrum are adults with no or only mild pulmonary vascular disease and a large
      shunt. These are patients who can safely undergo shunt closure. In the elderly,
      mild residual pulmonary hypertension after shunt closure is the rule. At the
      other end of the spectrum are adults with severe, irreversible pulmonary vascular
      disease, shunt reversal and chronic cyanosis, that is, Eisenmenger syndrome.
      These are patients who need to be managed medically. The challenge is to properly
      classify ASD patients with PAH falling in between the two ends of the spectrum as
      the ones with advanced, but reversible pulmonary vascular disease amenable to
      repair, versus the ones with progressive pulmonary vascular disease not
      responding to shunt closure. There are concerns that adults with progressive
      pulmonary vascular disease have worse outcomes after shunt closure than patients
      not undergoing shunt closure. Due to the correlation of pulmonary vascular
      changes and pulmonary hemodynamics, cardiac catheterization is used in the
      decision-making process. It is important to consider the hemodynamic data in the
      context of the clinical picture, the defect anatomy and further noninvasive tests
      when evaluating the option of shunt closure in these patients. 

PMID- 25982880
TI  - Nuclear cardiac myosin light chain 2 modulates NADPH oxidase 2 expression in
      myocardium: a novel function beyond muscle contraction.
AB  - Recent studies demonstrated that NADPH oxidase 2 (NOX2) expression in myocardium
      after ischemia-reperfusion (IR) is significantly upregulated. However, the
      underlying mechanisms remain unknown. This study aims to determine if nuclear
      cardiac myosin light chain 2 (MYL2), a well-known regulatory subunit of myosin,
      functions as a transcription factor to promote NOX2 expression following
      myocardial IR in a phosphorylation-dependent manner. We examined the
      phosphorylation status of nuclear MYL2 (p-MYL2) in a rat model of myocardial IR
      (left main coronary artery subjected to 1 h ligation and 3 h reperfusion) injury,
      which showed IR injury and upregulated NOX2 expression as expected, accompanied
      by elevated H2O2 and nuclear p-MYL2 levels; these effects were attenuated by
      inhibition of myosin light chain kinase (MLCK). Next, we explored the functional
      relationship of nuclear p-MYL2 with NOX2 expression in H9c2 cell model of hypoxia
      reoxygenation (HR) injury. In agreement with our in vivo findings, HR treatment
      increased apoptosis, NOX2 expression, nuclear p-MYL2 and H2O2 levels, and the
      increases were ameliorated by inhibition of MLCK or knockdown of MYL2. Finally,
      molecular biology techniques including co-immunoprecipitation (Co-IP), chromatin
      immunoprecipitation (ChIP), DNA pull-down and luciferase reporter gene assay were
      utilized to decipher the molecular mechanisms. We found that nuclear p-MYL2 binds
      to the consensus sequence AGCTCC in NOX2 gene promoter, interacts with RNA
      polymerase II and transcription factor IIB to form a transcription preinitiation
      complex, and thus activates NOX2 gene transcription. Our results demonstrate that
      nuclear MYL2 plays an important role in IR injury by transcriptionally
      upregulating NOX2 expression to enhance oxidative stress in a phosphorylation
      dependent manner.

PMID- 25982881
TI  - Myocardial mitochondrial dysfunction in mice lacking adiponectin receptor 1.
AB  - Hypoadiponectinemia is an independent predictor of cardiovascular disease,
      impairs mitochondrial function in skeletal muscle, and has been linked to the
      pathogenesis of Type 2 diabetes. In models of Type 2 diabetes, myocardial
      mitochondrial function is impaired, which is improved by increasing serum
      adiponectin levels. We aimed to define the roles of adiponectin receptor 1
      (AdipoR1) and 2 (AdipoR2) in adiponectin-evoked regulation of mitochondrial
      function in the heart. In isolated working hearts in mice lacking AdipoR1,
      myocardial oxygen consumption was increased without a concomitant increase in
      cardiac work, resulting in reduced cardiac efficiency. Activities of
      mitochondrial oxidative phosphorylation (OXPHOS) complexes were reduced,
      accompanied by reduced OXPHOS protein levels, phosphorylation of AMP-activated
      protein kinase, sirtuin 1 activity, and peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC-1alpha) signaling. Decreased ATP/O ratios
      suggested myocardial mitochondrial uncoupling in AdipoR1-deficient mice, which
      was normalized by lowering increased mitochondrial 4-hydroxynonenal levels
      following treatment with the mitochondria-targeted antioxidant Mn (III) tetrakis
      (4-benzoic acid) porphyrin. Lack of AdipoR2 did not impair mitochondrial function
      and coupling in the heart. Thus, lack of AdipoR1 impairs myocardial mitochondrial
      function and coupling, suggesting that impaired AdipoR1 signaling may contribute
      to mitochondrial dysfunction and mitochondrial uncoupling in Type 2 diabetic
      hearts. 

PMID- 25982882
TI  - Depressive symptoms predict the quality of sleep in patients with partial
      epilepsy--A combined retrospective and prospective study.
AB  - INTRODUCTION: Epilepsy is one of the most common neurological diseases and has
      many detrimental effects on the patients' well-being as well as sleep quality.
      The aim of this study was to assess the subjective quality of sleep and
      influencing factors on subjective sleep quality in patients with partial epilepsy
      using a combined retrospective and prospective study design. METHODS: We
      conducted a combined retrospective and prospective study in patients with partial
      epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17
      female, 15 male; mean age: 40.41 +/- 12.67 years, range: 20-64) with partial
      epilepsy (mean duration of epilepsy diagnosis: 18.31 +/- 13.26 years) and 32
      healthy gender-matched and age-matched controls. All patients filled out a
      seizure diary for 90 days, which included the number, duration, and type (partial
      vs. secondary generalized) of epileptic seizures and intake of antiepileptic and
      sleep medications. At baseline, all participants completed the Pittsburgh Sleep
      Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory
      (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI
      score of >= 5. RESULTS: Twenty-three patients (72%) reported 15.17 +/- 25.54
      seizures in the previous three months, and nine (28%) patients reported being
      seizure-free. During the 90-day diary period, twenty-two patients (69%)
      documented a total of 319 epileptic seizures, while ten patients (31%) reported
      that they were seizure-free. The mean PSQI score of all patients was 4.88 +/-
      2.92 (range: 1-14) and the mean ESS score was 5.25 +/- 2.98 (range: 0-10). The
      mean PSQI score of the control group was 3.25 +/- 1.57 (range: 1-6), and their
      mean ESS score was 6.72 +/- 3.48 (range: 0-14). The comparison of the two groups
      showed a significantly higher PSQI score in the patient group (t = 2.778, p =
      0.008), but no statistically significant difference regarding their ESS score (t
      = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers
      showed a significantly lower PSQI (2.69 +/- 1.08 vs. 7.06 +/- 2.49; p < 0.001)
      and BDI scores (2.38 +/- 2.50 vs. 9.63 +/- 7.63; p < 0.002) than poor sleepers.
      Linear regression analysis showed that the BDI score was the significant
      predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS
      score (estimate: 0.2251; p = 0.0321). CONCLUSION: In patients with partial
      epilepsy, a higher depression score was the best predictor for a poor subjective
      sleep quality and increased daytime sleepiness.

PMID- 25982883
TI  - Seizure occurrence and the circadian rhythm of cortisol: a systematic review.
AB  - PURPOSE: Stress is the seizure precipitant most often reported by patients with
      epilepsy or their caregivers. The relation between stress and seizures is
      presumably mediated by stress hormones such as cortisol, affecting neuronal
      excitability. Endogenous cortisol is released in a circadian pattern. To gain
      insight into the relation between the circadian rhythm of cortisol and seizure
      occurrence, we systematically reviewed studies on the diurnal distribution of
      epileptic seizures in children and adults and linked the results to the circadian
      rhythm of cortisol. METHODS: A structured literature search was conducted to
      identify relevant articles, combining the terms 'epilepsy' and 'circadian seizure
      distribution', plus synonyms. Articles were screened using predefined selection
      criteria. Data on 24-hour seizure occurrence were extracted, combined, and
      related to a standard circadian rhythm of cortisol. RESULTS: Fifteen relevant
      articles were identified of which twelve could be used for data aggregation.
      Overall, seizure occurrence showed a sharp rise in the early morning, followed by
      a gradual decline, similar to cortisol rhythmicity. The occurrence of generalized
      seizures and focal seizures originating from the parietal lobe in particular
      followed the circadian rhythm of cortisol. CONCLUSIONS: The diurnal occurrence of
      epileptic seizures shows similarities to the circadian rhythm of cortisol. These
      results support the hypothesis that circadian fluctuations in stress hormone
      level influence the occurrence of epileptic seizures.

PMID- 25982884
TI  - Social cognition dysfunctions in patients with epilepsy: Evidence from patients
      with temporal lobe and idiopathic generalized epilepsies.
AB  - BACKGROUND AND AIM: Despite an extensive literature on cognitive impairments in
      focal and generalized epilepsy, only a few number of studies specifically
      explored social cognition disorders in epilepsy syndromes. The aim of our study
      was to investigate social cognition abilities in patients with temporal lobe
      epilepsy (TLE) and in patients with idiopathic generalized epilepsy (IGE).
      MATERIALS AND METHODS: Thirty-nine patients (21 patients with TLE and 18 patients
      with IGE) and 21 matched healthy controls (HCs) were recruited. All subjects
      underwent a basic neuropsychological battery plus two experimental tasks
      evaluating emotion recognition from facial expression (Ekman-60-Faces test, Ek
      60F) and mental state attribution (Story-based Empathy Task, SET). In particular,
      the latter is a newly developed task that assesses the ability to infer others'
      intentions (i.e., intention attribution - IA) and emotions (i.e., emotion
      attribution - EA) compared with a control condition of physical causality (i.e.,
      causal inferences - CI). RESULTS: Compared with HCs, patients with TLE showed
      significantly lower performances on both social cognition tasks. In particular,
      all SET subconditions as well as the recognition of negative emotions were
      significantly impaired in patients with TLE vs. HCs. On the contrary, patients
      with IGE showed impairments on anger recognition only without any deficit at the
      SET task. DISCUSSION: Emotion recognition deficits occur in patients with
      epilepsy, possibly because of a global disruption of a pathway involving frontal,
      temporal, and limbic regions. Impairments of mental state attribution
      specifically characterize the neuropsychological profile of patients with TLE in
      the context of the in-depth temporal dysfunction typical of such patients.
      CONCLUSION: Impairments of socioemotional processing have to be considered as
      part of the neuropsychological assessment in both TLE and IGE in view of a
      correct management and for future therapeutic interventions.

PMID- 25982886
TI  - The Epilepsy Foundation is the Voice of People with Epilepsy and Their Families.

PMID- 25982885
TI  - Maternal immune activation increases seizure susceptibility in juvenile rat
      offspring.
AB  - Epidemiological data suggest a relationship between maternal infection and a high
      incidence of childhood epilepsy in offspring. However, there is little
      experimental evidence that links maternal infection with later seizure
      susceptibility in juvenile offspring. Here, we asked whether maternal immune
      challenge during pregnancy can alter seizure susceptibility and seizure
      associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated
      with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and
      16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated
      in male offspring. Four groups were studied, including normal control (NS-NS),
      prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA)
      groups. Our results demonstrated that maternal LPS exposure caused long-term
      reactive astrogliosis and increased seizure susceptibility in juvenile rat
      offspring. Compared to the juvenile seizure group, animals in the "two-hit" group
      showed exaggerated astrogliosis, followed by worsened spatial learning ability in
      adulthood. In addition, prenatal immune challenge alone led to spatial learning
      impairment in offspring but had no effect on anxiety. These data suggest that
      prenatal immune challenge causes a long-term increase in juvenile seizure
      susceptibility and exacerbates seizure-induced brain injury, possibly by priming
      astroglia. 

PMID- 25982887
TI  - Developing a Tailored Smoking Cessation Intervention for Rheumatoid Arthritis
      Patients.
AB  - PURPOSE: Smoking is associated with an increased risk of comorbidities in
      rheumatoid arthritis (RA) and may reduce the efficacy of anti-rheumatic
      therapies. Smoking cessation is therefore an important goal in RA. Our previous
      qualitative research identified five RA-related barriers to smoking cessation:
      lack of support; limited knowledge of the relationship between smoking and RA;
      uncontrolled pain; inability to exercise; and using smoking as a coping strategy.
      The aim of this article is to describe the process of developing a smoking
      cessation intervention for RA patients based on these themes. METHODS: A
      comprehensive review of the literature on smoking cessation was undertaken. A
      tailored smoking cessation programme was designed to address each RA-specific
      barrier. A meeting was convened with key staff of Arthritis New Zealand to
      develop a consensus on feasible design to deliver a smoking cessation programme
      based on existing best practice and smoking cessation resources, and tailored
      within existing Arthritis New Zealand service delivery frameworks. RESULTS: A
      three-month intervention was designed to be delivered by trained arthritis
      educators, with the following key components: nicotine replacement therapy for
      eight weeks; a telephone or face-to-face interview with each patient to determine
      their individual specific RA-related barriers to smoking cessation; and
      individualized education and support activities which addressed these barriers.
      The intervention also included three follow-up telephone calls; a support
      website; and 12 weekly smoking cessation advice emails. CONCLUSIONS: A RA
      specific smoking cessation invention was developed, matching support to specific
      issues within each patient's experience. A pilot study is in progress to evaluate
      the programme's efficacy. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25982888
TI  - Pruritic, Indurated Lesions on a Man's Forearms.

PMID- 25982889
TI  - Supramolecular self-assembly of linear oligosilsesquioxanes on mica--AFM surface
      imaging and hydrophilicity studies.
AB  - Linear oligomeric [2-(carboxymethylthio)ethylsilsesquioxanes] (LPSQ-COOH) adsorb
      spontaneously on muscovite mica and form smooth, well-ordered lamellar structures
      at the liquid-solid interface. Side carboxylic groups, having donor-acceptor
      character with regard to hydrogen bonds, are engaged both in multipoint molecule
      to-substrate interactions and intermolecular cross-linking. The unique
      arrangement of silsesquioxane macromolecules, with COOH groups situated at the
      interface with air, produces highly hydrophilic surfaces of good thermal and
      solvolytic stability. Supramolecular assemblies of LPSQ-COOH were studied using
      atomic force microscopy (AFM), angle-resolved X-ray photoelectron spectroscopy
      (ARXPS) and attenuated total reflectance (ATR) FTIR spectroscopy. Comparative
      height profile analysis combined with ATR-FTIR studies of the spectral regions
      characteristic of carboxylic groups and C1s core level envelope by XPS confirmed
      specific interactions between LPSQ-COOH and mica. 

PMID- 25982890
TI  - Non-hormonal targets underlying endometriosis: A focus on molecular mechanisms.
AB  - Endometriosis is regarded as a hormone-dependent disease. Current therapeutic
      approaches to treating this common gynecological disorder mainly depend on
      surgical and hormonal interventions, but the high rate of disease recurrence as
      well as the side effects related to such therapies make it difficult for patients
      to recover completely. Molecular evidence has recently suggested that the source
      of endometriosis can be both hormone-dependent and influenced by the
      dysregulation of some signaling cascades. In this review, we focus on the non
      hormonal triggers of endometriosis and the pre-clinical compounds designed to
      correct these signaling defects in order to achieve a better understanding of the
      disease as well as novel approaches to treating it.

PMID- 25982891
TI  - Systematic method for initial rapid analysis of maxillofacial computed tomography
      scans for surgeons in training.
AB  - BACKGROUND: Reading maxillofacial computed tomography (CT) scans is a basic skill
      for any surgeon who operates on the face. A standard systematic approach for how
      to read a maxillofacial CT scan from a surgeon's perspective is lacking in
      literature, particularly for those in the early stages of training. We present a
      method of initial rapid analysis which our residents in training have responded
      to and report to be conceptually simple to apply. METHODS: The senior author
      reviewed over 250 consults for face trauma and performed a detailed composite of
      the most common elements of each consult as well as the clinically relevant
      decision points. These elements were then bundled into a conceptual sketch of the
      skull-face-mandible with an accompanying standardized clinical data list. The new
      residents were then guided through a systematic approach to reading the scans
      while sketching the injuries identified. The authors then performed a survey to
      establish if the new method was helpful to early learners prior to and after
      adoption of the method. The survey consisted of five questions regarding the
      utility of the method for analysis of reading maxillofacial CT. RESULTS: In
      total, seven residents were surveyed; 100% thought the technique made reading
      facial CT easier, 100% thought this method was easy to teach to junior residents
      and 86% found the analysis of facial CT easier and helped their surgical decision
      making. CONCLUSION: We present a systematic method for surgeons to evaluate
      facial CT scans. This is the first published account of methodology for
      maxillofacial CT analysis for surgeons.

PMID- 25982893
TI  - High-resolution melting analysis of HPV-16L1 gene methylation: A promising method
      for prognosing cervical cancer.
AB  - OBJECTIVE: Methylation-sensitive high-resolution melting (MS-HRM) is a new
      technique for DNA methylation analysis, but it is rarely used for the detection
      of viral DNA methylation. In this study, we investigated the HPV-16L1 gene
      methylation that is detected by MS-HRM as a potential biomarker for prognosing
      cervical dysplasia and cancer. DESIGN AND METHODS: A total of 114 HPV-16 infected
      patients (normal (17), CIN1 (25), CIN2 (29), CIN3 (32), SCC (11)) who underwent
      liquid-based cytology test and biopsy were included in this study. 17 cases with
      HPV-16 infection and negative cytologic and histologic results served as the
      control group. The HPV-16L1 gene methylation statuses of these samples were
      investigated using a methylation-sensitive high-resolution melting (MS-HRM) assay
      after bisulfite modification. RESULTS: The HPV-16L1 gene methylation statuses of
      all the 114 specimens were successfully detected by MS-HRM, and we observed
      increasing methylation levels in severe lesions, as determined using histologic
      assays. In addition, the methylation levels of CIN2+ (CIN2, CIN3 and SCC) were
      significantly higher than that of CIN2- (normal and CIN1, P<0.001). When taking
      CIN2+ as the reference, our HPV-16L1 DNA methylation assay achieved 91.7%
      sensitivity and 59.5% specificity, respectively. CONCLUSIONS: The results of the
      present work demonstrated that HPV-16L1 gene methylation was closely associated
      with cervical precancerosis and cancer. Moreover, using MS-HRM to detect HPV-16L1
      gene methylation may be a powerful assay for the triage of HPV-16-positive
      females, which could identify patients with high risk of invasive cancer.

PMID- 25982892
TI  - Improved biomechanical and biological outcomes in the MRL/MpJ murine strain
      following a full-length patellar tendon injury.
AB  - Musculoskeletal injuries greatly affect the U.S. population and current clinical
      approaches fail to restore long-term native tissue structure and function. Tissue
      engineering is a strategy advocated to improve tendon healing; however, the field
      still needs to establish biological benchmarks for assessing the effectiveness of
      tissue-engineered structures. Investigating superior healing models, such as the
      MRL/MpJ, offers the opportunity to first characterize successful healing and then
      apply experimental findings to tissue-engineered therapies. This study seeks to
      evaluate the MRL/MpJ's healing response following a central patellar tendon
      injury compared to wildtype. Gene expression and histology were assessed at 3, 7,
      and 14 days following injury and mechanical properties were measured at 2, 5, and
      8 weeks. Native patellar tendon biological and mechanical properties were not
      different between strains. Following injury, the MRL/MpJ displayed increased
      mechanical properties between 5 and 8 weeks; however, early tenogenic expression
      patterns were not different between the strains. Furthermore, expression of the
      cyclin-dependent kinase inhibitor, p21, was not different between strains,
      suggesting an alternative mechanism may be driving the healing response. Future
      studies will investigate collagen structure and alignment of the repair tissue
      and characterize the complete healing transcriptome to identify mechanisms
      driving the MRL/MpJ response.

PMID- 25982895
TI  - Modeling of surface cleaning by cavitation bubble dynamics and collapse.
AB  - Surface cleaning using cavitation bubble dynamics is investigated numerically
      through modeling of bubble dynamics, dirt particle motion, and fluid material
      interaction. Three fluid dynamics models; a potential flow model, a viscous
      model, and a compressible model, are used to describe the flow field generated by
      the bubble all showing the strong effects bubble explosive growth and collapse
      have on a dirt particle and on a layer of material to remove. Bubble deformation
      and reentrant jet formation are seen to be responsible for generating
      concentrated pressures, shear, and lift forces on the dirt particle and high
      impulsive loads on a layer of material to remove. Bubble explosive growth is also
      an important mechanism for removal of dirt particles, since strong suction forces
      in addition to shear are generated around the explosively growing bubble and can
      exert strong forces lifting the particles from the surface to clean and sucking
      them toward the bubble. To model material failure and removal, a finite element
      structure code is used and enables simulation of full fluid-structure interaction
      and investigation of the effects of various parameters. High impulsive pressures
      are generated during bubble collapse due to the impact of the bubble reentrant
      jet on the material surface and the subsequent collapse of the resulting toroidal
      bubble. Pits and material removal develop on the material surface when the
      impulsive pressure is large enough to result in high equivalent stresses
      exceeding the material yield stress or its ultimate strain. Cleaning depends on
      parameters such as the relative size between the bubble at its maximum volume and
      the particle size, the bubble standoff distance from the particle and from the
      material wall, and the excitation pressure field driving the bubble dynamics.
      These effects are discussed in this contribution. 

PMID- 25982894
TI  - Quantification of mevalonate-5-phosphate using UPLC-MS/MS for determination of
      mevalonate kinase activity.
AB  - OBJECTIVES: Mevalonate kinase deficiency, a rare autosomal recessive
      autoinflammatory disease, is caused by mutations in the MVK gene encoding
      mevalonate kinase (MK). MK catalyzes the phosphorylation of mevalonic acid to
      mevalonate-5-phosphate (MVAP) in the pathway of isoprenoid and sterol synthesis.
      The disease phenotype correlates with residual activity ranging from <0.5% for
      mevalonic aciduria to 1-7% for the milder hyperimmunoglobulinemia D and periodic
      fever syndrome (HIDS). Hence, assessment of loss-of-function requires high
      accuracy measurements. We describe a method using isotope dilution UPLC-MS/MS for
      precise and sensitive determination of MK activity. DESIGN AND METHODS: Wild-type
      MK and the variant V261A, which is associated with HIDS, were recombinantly
      expressed in Escherichia coli. Enzyme activity was determined by formation of
      MVAP over time quantified by isotope dilution UPLC-MS/MS. The method was
      validated according to the FDA Guidance for Bioanalytical Method Validation.
      RESULTS: Sensitivity for detection of MAVP by UPLC-MS/MS was improved by
      derivatization with butanol-HCl (LLOQ, 5.0 fmol) and the method was linear from
      0.5 to 250 MUmol/L (R(2) > 0.99) with a precision of >= 89% and an accuracy of +/
      2.7%. The imprecision of the activity assay, including the enzymatic reaction
      and the UPLC-MS/MS quantification, was 8.3%. The variant V261A showed a
      significantly decreased activity of 53.1%. CONCLUSION: Accurate determination of
      MK activity was enabled by sensitive and reproducible detection of MVAP using
      UPLC-MS/MS. The novel method may improve molecular characterization of MVK
      mutations, provide robust genotype-phenotype correlations, and accelerate
      compound screening for drug candidates restoring variant MK activity.

PMID- 25982896
TI  - Acute myocardial infarction activates distinct inflammation and proliferation
      pathways in circulating monocytes, prior to recruitment, and identified through
      conserved transcriptional responses in mice and humans.
AB  - AIMS: Monocytes play critical roles in tissue injury and repair following acute
      myocardial infarction (AMI). Specifically targeting inflammatory monocytes in
      experimental models leads to reduced infarct size and improved healing. However,
      data from humans are sparse, and it remains unclear whether monocytes play an
      equally important role in humans. The aim of this study was to investigate
      whether the monocyte response following AMI is conserved between humans and mice
      and interrogate patterns of gene expression to identify regulated functions.
      METHODS AND RESULTS: Thirty patients (AMI) and 24 control patients (stable
      coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group)
      underwent AMI by surgical coronary ligation. Myocardial injury was quantified by
      magnetic resonance imaging (human) and echocardiography (mice). Peripheral
      monocytes were isolated at presentation and at 48 h. RNA from separated monocytes
      was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a
      significant peripheral monocytosis in both species that positively correlated
      with the extent of myocardial injury. Analysis of the monocyte transcriptome
      following AMI demonstrated significant conservation and identified inflammation
      and mitosis as central processes to this response. These findings were validated
      in both species. CONCLUSIONS: Our findings show that the monocyte transcriptome
      is conserved between mice and humans following AMI. Patterns of gene expression
      associated with inflammation and proliferation appear to be switched on prior to
      their infiltration of injured myocardium suggesting that the specific targeting
      of inflammatory and proliferative processes in these immune cells in humans are
      possible therapeutic strategies. Importantly, they could be effective in the
      hours after AMI.

PMID- 25982897
TI  - Clinically relevant anatomical parameters of the replaced right hepatic artery
      (RRHA).
AB  - PURPOSE: Vascular anatomy of the liver is subjected to many variations. The most
      common hepatic artery (HA) replacement is the right hepatic artery (RRHA).
      Variations of the HA are particularly important consideration when choosing the
      best surgical procedure or if radiological abdominal intervention is required. In
      this study, we evaluated the anatomical details of the RRHA origin. METHODS:
      Retrospective investigation of clinical data from 1569 patients who underwent an
      abdominal MDCT was performed. The anatomy of RRHA origin was described based on
      four parameters measured: D--the distance between SMA origin and the RRHA origin,
      L--the lumen at the place of origin, AH--the origin angle from the SMA in
      horizontal plane, and AV--the origin angle from the SMA in vertical plane.
      RESULTS: RRHA arising from SMA was detected in 10.13 % of cases (159/1569) and
      its anatomy was subjected to variations. Mean (+/-SD) of parameters D, L, AH and
      AV was 27.34 mm +/- 6.83, 3.29 mm +/- 1.17, 97.27o +/- 26.69 and 89.73o +/-
      20.81, respectively. Values of parameters D and L were significantly higher in
      males compared to females. CONCLUSION: Although radiologists are not always aware
      of the clinical significance of the RRHA origin, the evaluation of its anatomy is
      thought to help reduce the risk of inadvertent vascular injury, especially in
      pancreatoduodenectomy. Detection and evaluation of the RRHA does not necessarily
      require angio-CT examination. Our study demonstrated that the MDCT, the standard
      imaging modality for diagnosing the abdominal symptoms, is sufficient to provide
      the knowledge of the HA abnormalities.

PMID- 25982898
TI  - Pigmented squamous cell carcinoma of the cheek and its dermoscopic features.

PMID- 25982899
TI  - Human calicivirus occurrence among outpatients with diarrhea in Beijing, China,
      between April 2011 and March 2013.
AB  - Human caliciviruses (HuCVs), including noroviruses (NoVs) and sapoviruses (SaVs),
      are the most common cause of diarrhea in adults and the second most common cause
      of diarrhea in children. Between April 2011 and March 2013, 3,832 fecal specimens
      were collected from outpatients with diarrhea from 17 hospitals in Beijing,
      China, and 669 specimens (17.5%) were positive for HuCV. Of the 287 HuCV-positive
      specimens, 263 (91.6%) were identified to be NoV, 23 (8.0%) were identified to be
      SaV, and one (0.3%) was identified to be a mixed infection of NoV and SaV. Of the
      263 NoV-positive specimens, 237 (90.1%) were NoV GII, 21 (8.0%) were NoV GI, and
      5 (1.9%) were a combination of NoV GI and GII. Among the 216 sequenced GII
      positive samples, GII.4 was the most common genotype (70.4%, 152/216), followed
      by GII.13 (9.3%, 20/216). GII.4 Sydney_2012 was first detected in August 2012 and
      replaced GII.4 Den Haag_2006b as the predominant variant between September 2012
      and March 2013. With the emergence of the GII.4 Sydney_2012 variant, 44.6% more
      patients with diarrhea visited the 17 hospitals (9,931 cases) than in the
      previous year (6,866 cases) between October and December 2012.

PMID- 25982900
TI  - 40th annual meeting-nice, france june 9-13, 2015: oral presentations.

PMID- 25982901
TI  - 40th annual meeting - nice, france june 9 - 13, 2015.

PMID- 25982902
TI  - WCAPP presentations.

PMID- 25982903
TI  - WCAPP - oral podium presentations.

PMID- 25982905
TI  - Household coping strategies for delivery and related healthcare cost: findings
      from rural Bangladesh.
AB  - OBJECTIVES: This study aims to measure the economic costs of maternal
      complication and to understand household coping strategies for financing maternal
      healthcare cost. METHODS: A household survey of the 706 women with maternal
      complication, of whom 483 had normal delivery, was conducted to collect data at 6
      weeks and 6 months post-partum. Data were collected on socio-economic information
      of the household, expenditure during delivery and post-partum, coping strategies
      adopted by households and other related information. RESULTS: Despite the high
      cost of health care associated with maternal complications, the majority of
      families were capable of protecting consumption on non-health items. Around one
      third of households spent more than 20% of their annual household expenditure on
      maternal health care. Almost 50% were able to avoid catastrophic spending because
      of the coping strategies that they relied on. In general, households appeared
      resilient to short-term economic consequences of maternal health shocks, due to
      the availability of informal credit, donations from relatives and selling assets.
      While richer households fund a greater portion of the cost of maternal health
      care from income and savings, the poorer households with severe maternal
      complication resorted to borrowing from local moneylenders at high interest,
      which may leave them vulnerable to financial difficulties. CONCLUSION: Financial
      protection, especially for the poor, may benefit households against economic
      consequences of maternal complication.

PMID- 25982906
TI  - The impact of discussing exercise test results of young asthmatic children on
      adherence to maintenance medication.
AB  - OBJECTIVE: Parents' awareness of their child's asthma may improve by discussing
      an exercise challenge test (ECT) result with them. We investigated the influence
      of discussing an ECT result with parents on adherence to inhaled maintenance
      medication, parental illness perceptions and medication beliefs in young
      asthmatic children. METHODS: A total of 79 children, 4-7 years old and enrolled
      in our standard comprehensive asthma care program, performed an ECT to assess
      exercise induced bronchoconstriction (EIB). The result of the ECT was immediately
      discussed with the parents. Median medication adherence level was measured with
      electronic medication loggers from six weeks before the ECT till six weeks
      afterwards. Parental beliefs about medicines and illness perceptions were
      measured with the Beliefs about Medicines Questionnaire (BMQ) and the Brief
      Illness Perceptions Questionnaire (B-IPQ). RESULTS: The median baseline adherence
      level was high (83%) and showed a small significant decline after the ECT. There
      was no significant difference in the decrease in median adherence level between
      the children with or without EIB. Most parents (82.1%) showed a positive
      necessity-concern ratio at baseline, as measured with the BMQ. There was no
      clinical relevant change in medication concerns and necessity scores or in
      illness perceptions. CONCLUSION: Discussing ECT results with parents does not
      modify median adherence levels to inhaled maintenance medication nor medication
      beliefs of highly adherent young asthmatic children who are already enrolled in a
      comprehensive asthma care program.

PMID- 25982907
TI  - Insulin therapy in hyperglycemic children with severe acute asthma.
AB  - OBJECTIVES: The aim of this study was to assess the effect of intravenous (IV)
      insulin administration in children with severe acute asthma (SAA) and
      hyperglycemia on IV salbutamol consumption and length of stay (LOS) in a
      pediatric intensive care unit (PICU). METHODS: Retrospective, descriptive study
      of the clinical course before and after implementation of an insulin protocol for
      the treatment of hyperglycemia (i.e. blood glucose >8 mmol/L or 144 mg/dL,
      respectively) in the PICU of a tertiary care university hospital. Admissions
      between 1994 and 2010 were reviewed. The insulin protocol was introduced in 2006.
      RESULTS: A total of 131 pediatric patients with SAA complicated by hyperglycemia
      requiring IV salbutamol were included. Severity of illness before and after
      implementation of the insulin protocol did not significantly differ. The insulin
      treated patient group had significantly higher maximum blood glucose levels and
      higher cumulative IV salbutamol dose than the non-treated group. There were no
      differences between these groups in the duration of IV salbutamol administration
      and LOS. CONCLUSIONS: In view of the lack of difference in outcomes and
      considering that the insulin protocol is labor-intensive, the question is whether
      this protocol is efficacious for the treatment of pediatric SAA associated with
      hyperglycemia.

PMID- 25982908
TI  - A label fusion method using conditional random fields with higher-order
      potentials: Application to hippocampal segmentation.
AB  - OBJECTIVE: The objective of this study is to develop a probabilistic modeling
      framework for segmenting structures of interest from a collection of atlases. We
      present a label fusion method that is based on minimizing an energy function
      using graph-cut techniques. METHODS AND MATERIALS: We use a conditional random
      field (CRF) model that allows us to efficiently incorporate shape, appearance and
      context information. This model is characterized by a pseudo-Boolean function
      defined on unary, pairwise and higher-order potentials. Given a subset of
      registered atlases in the target image for a particular region of interest (ROI),
      we first derive an appearance-shape model from these registered atlases. The
      unary potentials combine an appearance model based on multiple features with a
      label prior using a weighted voting method. The pairwise terms are defined from a
      Finsler metric that minimizes the surface of separation between voxels whose
      labels are different. The higher-order potentials used in our framework are based
      on the robust P(n) model proposed by Kohli et al. The higher-order potentials
      enforce label consistency in cliques; hence, the proposed method can be viewed as
      an approach to integrate high-level information with images based on low-level
      features. To evaluate the performance and the robustness of the proposed label
      fusion method, we employ two available databases of T1-weighted (T1W) magnetic
      resonance (MR) images of human brains. We compare our approach with other label
      fusion methods in the automatic hippocampal segmentation from T1W-MR images.
      RESULTS: Our label fusion method yields mean Dice coefficients of 0.829 and 0.790
      for the two databases used with mean times of approximately 80 and 160s,
      respectively. CONCLUSIONS: We introduce a new label fusion method based on a CRF
      model and on ROIs. The CRF model is characterized by a pseudo-Boolean function
      defined on unary, pairwise and higher-order potentials. The proposed Boolean
      function is representable by graphs. A globally optimal binary labeling is found
      using a st-mincut algorithm in each ROI. We show that the proposed approach is
      very competitive with respect to recently reported methods.

PMID- 25982909
TI  - Sentiment analysis in medical settings: New opportunities and challenges.
AB  - OBJECTIVE: Clinical documents reflect a patient's health status in terms of
      observations and contain objective information such as descriptions of
      examination results, diagnoses and interventions. To evaluate this information
      properly, assessing positive or negative clinical outcomes or judging the impact
      of a medical condition on patient's well being are essential. Although methods of
      sentiment analysis have been developed to address these tasks, they have not yet
      found broad application in the medical domain. METHODS AND MATERIAL: In this
      work, we characterize the facets of sentiment in the medical sphere and identify
      potential use cases. Through a literature review, we summarize the state of the
      art in healthcare settings. To determine the linguistic peculiarities of
      sentiment in medical texts and to collect open research questions of sentiment
      analysis in medicine, we perform a quantitative assessment with respect to word
      usage and sentiment distribution of a dataset of clinical narratives and medical
      social media derived from six different sources. RESULTS: Word usage in clinical
      narratives differs from that in medical social media: Nouns predominate. Even
      though adjectives are also frequently used, they mainly describe body locations.
      Between 12% and 15% of sentiment terms are determined in medical social media
      datasets when applying existing sentiment lexicons. In contrast, in clinical
      narratives only between 5% and 11% opinionated terms were identified. This proves
      the less subjective use of language in clinical narratives, requiring adaptations
      to existing methods for sentiment analysis. CONCLUSIONS: Medical sentiment
      concerns the patient's health status, medical conditions and treatment. Its
      analysis and extraction from texts has multiple applications, even for clinical
      narratives that remained so far unconsidered. Given the varying usage and
      meanings of terms, sentiment analysis from medical documents requires a domain
      specific sentiment source and complementary context-dependent features to be able
      to correctly interpret the implicit sentiment.

PMID- 25982910
TI  - How can [Mo(IV)(CN)6](2-), an apparently octahedral (d)(2) complex, be
      diamagnetic? Insights from quantum chemical calculations and magnetic
      susceptibility measurements.
AB  - Quantum chemical calculations are employed to elucidate the origin of a puzzling
      diamagnetism for a hexacyanomolybdate(IV) anion, [Mo(CN)6](2-), which was
      previously reported by Szklarzewicz et al. [Inorg. Chem., 2007, 46, 9531-9533].
      The diamagnetism is surprising because for the octahedral (d)(2) complex one
      would rather expect a (paramagnetic) triplet ground state, clearly favored over a
      (diamagnetic) singlet state by an exchange interaction between two d electrons in
      the t2g orbitals. Nevertheless, the present calculations reveal that the minimum
      energy structure of isolated [Mo(CN)6](2-) is not an octahedron, but a trigonal
      prism; the latter geometry allows maximization of a sigma-donation from the
      cyanides to the electron-deficient Mo(iv) center. Unlike for the octahedron, for
      the trigonal prism structure the singlet and triplet spin states are close in
      energy to within a few kcal mol(-1). Although the actual relative energy of the
      two spin states turns out to be method-dependent, the complete active space
      calculations (CASPT2; with the appropriate choice of the IPEA shift parameter)
      can reproduce the singlet ground state, in agreement with the experimentally
      observed diamagnetism. Moreover, magnetic measurements reveal a slight increase
      of the magnetic susceptibility with the increase of temperature from 100 to 300
      K, suggesting an admixture of a thermally induced paramagnetism (possibly due to
      Boltzmann population of the low-energy triplet state) on top of the dominant
      diamagnetism. Our prediction that the geometry of [Mo(CN)6](2-) should
      significantly deviate from the ideal octahedron, not only in the gas phase, but
      also in a periodic DFT model of the crystalline phase, as well as the
      experimentally confirmed diamagnetic properties, does not agree with the
      previously reported ideal octahedral structure. We suggest that this crystal
      structure might have been determined incorrectly (e.g., due to overlooked
      merohedral twinning or superstructure properties) and it should be re
      investigated.

PMID- 25982911
TI  - The deregulated expression of miR-125b in acute myeloid leukemia is dependent on
      the transcription factor C/EBPalpha.

PMID- 25982912
TI  - Interhospital spread of NDM-7-producing Klebsiella pneumoniae belonging to ST437
      in Spain.
AB  - This study describes an interhospital spread of carbapenem-resistant Klebsiella
      pneumoniae (CRKP) producing NDM-7 carbapenemase that started in December 2013 in
      Madrid, Spain. NDM-7-producing CRKP were isolated from urine, rectal swabs or
      blood samples from seven patients admitted to three different hospitals (Hospital
      Universitario La Paz, Hospital de Cantoblanco and Hospital Central de la Cruz
      Roja). The isolates were resistant to all antimicrobials tested except colistin
      and fosfomycin. One blood isolate was susceptible to minocycline and tigecycline
      but was resistant to fosfomycin. All isolates were closely related by pulsed
      field gel electrophoresis (PFGE) and DiversiLab((r)) analysis and belonged to
      multilocus sequence typing (MLST) sequence type 437. In addition, blaNDM-7,
      blaTEM-1, blaCTX-M-15 and aac(3)-IIa were identified. Family contacts of the
      index case were negative for NDM-producing bacteria. The outbreak occurred in two
      separate waves and the cases associated with Hospital de Cantoblanco had been
      admitted to the same room. Environmental samples from the trap of a sink and a
      shower in this room were positive for NDM-7-producing CRKP. To our knowledge,
      this is the first reported worldwide outbreak of NDM-7-producing CRKP. No
      relationship with the Indian continent, the Balkans or the Middle East could be
      established. Frequent transfer of aged or chronically ill patients between the
      facilities involved may have favoured the spread of NDM-7-producing CRKP. The
      spread of the second wave in Hospital de Cantoblanco probably occurred as a
      result of transmission from an environmental reservoir. 

PMID- 25982913
TI  - Review of meta-analyses of vancomycin compared with new treatments for Gram
      positive skin and soft-tissue infections: Are we any clearer?
AB  - Vancomycin has been considered the standard of care for treatment of Gram
      positive skin and soft-tissue infections (SSTIs). Its value has been questioned
      over the last decade owing to well acknowledged limitations in efficacy and
      tolerability and the emergence of newer meticillin-resistant Staphylococcus
      aureus (MRSA)-active antibacterial agents. However, no single agent has shown
      better results versus vancomycin in SSTI trials. The aim of this review was to
      identify and summarise data from meta-analyses (MAs) for the treatment of Gram
      positive and MRSA SSTIs. A systematic search identified 21 published MAs
      examining the use of newer antibiotics and vancomycin in SSTIs. In terms of
      clinical and microbiological efficacy, linezolid (in Gram-positive and MRSA
      SSTIs) and telavancin (in MRSA SSTIs) were shown to be more effective than
      vancomycin. The safety of newer antimicrobials in general was comparable with
      vancomycin, except for telavancin, which was associated with more severe adverse
      events (AEs), and tigecycline owing to an all-cause mortality imbalance observed
      in all infections but not confirmed in SSTIs. Specific AEs were related to the
      use of newer agents, such as nephrotoxicity for telavancin, creatine
      phosphokinase elevations for daptomycin, and thrombocytopenia with linezolid.
      Some evidence suggests that daptomycin could be associated with reduced treatment
      duration, and linezolid with reduced length of intravenous treatment and hospital
      length of stay compared with vancomycin. Considering the limitations of this type
      of research and the comparative efficacy results demonstrated in head-to-head
      randomised controlled trials, data are still not sufficient to support the
      widespread use of new agents over vancomycin. 

PMID- 25982914
TI  - Genotype-specific prevalence of heterogeneous vancomycin-intermediate
      Staphylococcus aureus in Asian countries.
AB  - Although heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) has
      been increasingly reported, the true prevalence of hVISA is unclear, especially
      in Asia. In this study, the genotype-specific prevalence of hVISA among
      meticillin-resistant S. aureus (MRSA) clinical isolates collected from Asian
      countries was determined. Among MRSA collections from South Korea, Taiwan, Hong
      Kong, Thailand, the Philippines, Vietnam, India and Sri Lanka in the ANSORP
      surveillance study during 2004 and 2006, isolates with a vancomycin minimum
      inhibitory concentration of >=0.25mg/L were randomly selected. After screening by
      macro Etest, hVISA was confirmed using the modified population analysis profile
      method. MRSA isolates were typed by spa tying and multilocus sequence typing
      (MLST). Among 462 MRSA isolates, 16 (3.5%) were confirmed as hVISA. The
      proportion of hVISA was highest in South Korea and Vietnam (both 7.0%), followed
      by Thailand (3.2%) and Taiwan (1.9%). spa type t601 belonging to clonal complex
      (CC) 5 showed the highest proportion of hVISA (33.3%), and hVISA accounted for
      6.9% among isolates of t002 belonging to CC5. Among CC239 isolates, only those of
      t037 were hVISA (1.6%). Among isolates of community-associated MRSA genotypes,
      hVISA was found only in those of t437 (4.8%) belonging to CC59, and no hVISA was
      found among those of CC30 or CC72. The prevalence of hVISA in the Asian region
      differed by country and was dependent upon the genotype of MRSA strains. It
      suggests that differences in hVISA prevalence between countries can be affected
      by the genotype distribution of MRSA strains. 

PMID- 25982915
TI  - Is tigecycline a suitable option for Clostridium difficile infection? Evidence
      from the literature.
AB  - Clostridium difficile infection (CDI) has become the most frequent cause of
      nosocomial infectious diarrhoea in developed countries, causing an increase in
      mortality, recurrences or treatment failure. In the search for new and more
      effective drugs, researchers recently turned their attention to tigecycline, a
      broad-spectrum antibiotic of the glycylglycine class available as an intravenous
      formulation for human use, which has also shown in vitro activity against C.
      difficile. We performed a literature review of articles addressing in vitro as
      well as in vivo studies and case reports on the effectiveness of tigecycline,
      whose use is promising especially in light of its high faecal excretion. The
      available evidence suggests that tigecycline could play a role as an alternative
      therapeutic option for critically ill patients or cases of refractory CDI. 

PMID- 25982916
TI  - Changes in the pharmacokinetics of teicoplanin in patients with hyperglycaemic
      hypoalbuminaemia: Impact of albumin glycosylation on the binding of teicoplanin
      to albumin.
AB  - There is large interindividual variability in serum teicoplanin (TEIC)
      concentrations after administration of a loading dose, and the factors that
      influence the pharmacokinetics of TEIC are disputed. The aim of this study was to
      clarify changes in the pharmacokinetics of TEIC that occur in patients with
      hyperglycaemia as well as the impact of albumin glycosylation on the
      pharmacokinetics of TEIC. This study consisted of retrospective and prospective
      investigations. The pharmacokinetic parameters of TEIC were retrospectively
      compared between patients receiving TEIC treatment. Ninety-four patients were
      divided into four groups according to their serum albumin and blood glucose
      concentrations [(i) hyperglycaemic hypoalbuminaemia (albumin<3.0g/dL) (n=16);
      (ii) non-hyperglycaemic hypoalbuminaemia (n=29); (iii) hyperglycaemic
      normoalbuminaemia (albumin>=3.0g/dL) (n=9); and (iv) non-hyperglycaemic
      normoalbuminaemia (n=40)]. In addition, the concentration of glycosylated albumin
      was prospectively determined in 28 patients. At 12h after administration of a
      loading dose, patients with hyperglycaemic hypoalbuminaemia displayed
      significantly lower serum TEIC concentrations (P<0.05) and higher TEIC volume of
      distribution (Vd) (P<0.05) than the other three groups, whereas TEIC clearance
      did not differ significantly among the groups. In addition, the percentage of
      glycosylated albumin was significantly correlated with the association constant
      (Ka) of TEIC for albumin (r=0.53, P=0.004) and the Vd (r=0.41, P=0.031). These
      results suggest that hyperglycaemic hypoalbuminaemia lowers the serum TEIC
      concentration, which is attributable to the decreased Ka and increased Vd of TEIC
      by albumin glycosylation. 

PMID- 25982917
TI  - Early goal-directed therapy vs usual care in the treatment of severe sepsis and
      septic shock: a systematic review and meta-analysis.
AB  - Sepsis is a common and high-burden healthcare problem with a mortality exceeding
      20 % in severe sepsis and nearly 50 % when septic shock is present. Early goal
      directed therapy (EGDT) is recommended by sepsis guidelines as the standard of
      care following a landmark study by Rivers et al. alongside other observational
      studies. Three recent randomized controlled trials have questioned the Rivers'
      results. The objective of our systematic review was to assess the effectiveness
      of EGDT in reducing the mortality of severe sepsis or septic shock. Relevant
      primary studies were identified by searching the MEDLINE and EMBASE databases and
      the Cochrane Central Register of Controlled Clinical Trials to identify
      randomized controlled trials assessing the effectiveness of EGDT for sepsis. Data
      from all trials were combined and analyzed using a random effects model. Five
      studies, enrolling a total of 4033 patients, were included in the meta-analysis.
      In-hospital mortality did not differ between the two treatment groups (RR 0.93,
      95 % CI 0.77-1.11, P = 0.42), although moderate heterogeneity between studies was
      noted (I (2) = 48 %). A non-significant trend toward reduction in 60-day
      mortality in the EGDT group was noted (RR 0.93, 95 % CI 0.82-1.05, P = 0.22, I
      (2) = 24 %). Heterogeneity between trials precludes a definitive conclusion on
      the utility of EGDT in severe sepsis. Until further evidence is available, it is
      reasonable to consider EGDT in the care of patients with severe sepsis and septic
      shock.

PMID- 25982918
TI  - Non-vitamin K oral anticoagulants in patients with pulmonary embolism: a
      systematic review and meta-analysis of the literature.
AB  - Limited information exists on the safety and efficacy of non-vitamin K oral
      anticoagulants (NOACs) in patients with pulmonary embolism (PE). The aim of this
      study is to evaluate the difference in the safety and efficacy of the NOACs in
      comparison to the standard treatment in patients presenting with deep vein
      thrombosis (DVT) and with PE using data from randomized controlled trials.
      MEDLINE and EMBASE databases were searched. Differences in the efficacy
      (recurrent VTE or death-related VTE) and in the safety (major bleeding) outcome
      were expressed as risk ratio (RR) with 95% confidence intervals (95% CI).
      Heterogeneity among the studies was assessed. Six studies (27,023 patients) were
      included. NOACs appeared to have a similar efficacy and safety compared to VKAs
      in patients presenting with PE and with DVT with a non-significant heterogeneity
      between the groups (efficacy: RR 0.90, 95% CI 0.72, 1.13 in PE patients and 0.93,
      95% CI 0.75, 1.16 in DVT patients; chi2 0.04, p = 0.84; safety: RR 0.49, 95% CI
      0.26, 0.95 in PE patients and 0.74 95% CI 0.51, 1.06 in DVT; chi2 1.10, p =
      0.29). Our results suggest that the efficacy and safety of the NOACs compared to
      VKAs is similar between patients with PE and DVT.

PMID- 25982919
TI  - Metabolic syndrome in castration-resistant prostate cancer patients treated with
      abiraterone.
AB  - BACKGROUND: Metabolic syndrome (MS) has not yet been studied in castration
      resistant prostate cancer (CRPC) men treated with novel hormonal therapies. The
      study aims to assess the impact of MS on outcome from time starting abiraterone.
      PATIENTS AND METHODS: We retrospectively evaluated a consecutive series of
      metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as
      defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the
      time of initiation of abiraterone, during treatment and follow-up. RESULTS: Sixty
      seven of 178 patients evaluated (37.6%) met MS criteria at baseline, before
      abiraterone initiation, whereas for 11 (9.9%) without MS before treatment with
      abiraterone this occurred during treatment. Median PFS was equal to 4.7 months
      for patients with MS versus 9 months for those without MS. Patients with MS had
      an increased risk of 71% of progression or death for all causes than patients
      without MS (HR = 1.7, 95% CI [1.2-2.4], P = 0.03). Median OS was 14.7 months and
      22.3 months in patients with and without MS, respectively. After adjusting for
      covariates, MS resulted not significantly associated to OS (HR = 1.42, 95% CI
      [0.91-2.22], P = 0.073). CONCLUSIONS: The presence of MS is a significant risk
      factor for shorter PFS in CRPC patients treated with abiraterone, even if it does
      not show a significant impact on OS. A prospective evaluation is warranted.

PMID- 25982920
TI  - Statin use prior to angiography for the prevention of contrast-induced acute
      kidney injury: a meta-analysis of 19 randomised trials.
AB  - AIMS: A systematic review and a meta-analysis were performed to define better the
      role of statin use prior to angiography in preventing contrast-induced acute
      kidney injury (CI-AKI). METHODS AND RESULTS: MEDLINE, Embase, Cochrane Library,
      references from review articles, and conference proceedings were searched, with
      no language restriction, for randomised controlled trials (RCT) evaluating the
      use of statin therapy prior to angiography for the prevention of CI-AKI. Nineteen
      RCTs including 7,161 patients were identified. The pooled analysis demonstrated a
      significant reduction in the incidence of CI-AKI in patients treated with statin
      prior to invasive angiography when compared with control (RR 0.52; 95% CI: 0.40
      0.67). Patients with chronic kidney disease stage 3 or worse were largely
      underrepresented in these trials, and statin therapy did not significantly reduce
      the risk of CI-AKI in the three studies which enrolled a patient population with
      a mean eGFR of <60 ml/min (RR 0.54; 95% CI: 0.2-1.42). CONCLUSIONS: This meta
      analysis suggests a potential benefit for statin use prior to angiography to
      reduce the incidence of CI-AKI. Additional research is needed to define better
      the benefits of statin therapy prior to angiography to prevent CI-AKI, especially
      in high-risk patients with chronic kidney disease who were largely
      underrepresented in the available trials.

PMID- 25982921
TI  - Impact of post-dilation on the acute and one-year clinical outcomes of a large
      cohort of patients treated solely with the Absorb Bioresorbable Vascular
      Scaffold.
AB  - AIMS: We sought to determine the impact of post-dilation (PD) on clinical
      outcomes in a large cohort of patients treated only with the Absorb Bioresorbable
      Vascular Scaffold (BVS). METHODS AND RESULTS: We evaluated all consecutive
      patients enrolled in the multicentre, single-arm ABSORB EXTEND study up to June
      2013. The study allowed treatment of up to two coronaries (diameter 2.0 to 3.8
      mm) and the use of overlapping (lesion length <=28 mm). Patients with severe
      lesion calcification/tortuosity were excluded. Aggressive lesion predilation
      (balloon to artery ratio of 0.9-1.0) was mandatory, and PD was left to the
      operator's discretion. Patients were grouped according to whether PD was
      performed or not, and the one-year incidences of MACE and scaffold thrombosis
      were compared. A total of 768 patients were enrolled in the study; PD was
      performed in 526 (68.4%). There were no significant differences between the PD
      group and non-PD group in the majority of baseline characteristics, including the
      presence of moderate calcification and of B2/C lesions. Lesion length was similar
      (12.3+/-5.1 mm vs. 12.1+/-5.3 mm, p=0.6), as was RVD (2.6 mm for both groups,
      p=0.2). Residual in-scaffold stenosis (15.5+/-6.4% with PD, 15.0+/-6% without PD,
      p=0.3) and the need for bail-out scaffold/stent (4.2% with PD, 4.6% without PD,
      p=0.8) were comparable. Acute gain was higher in the non-PD group (1.14+/-0.3 mm
      vs. 1.21+/-0.4 mm, p=0.02). Clinical device success was 98.9% in both groups. At
      one year, there was no difference in MACE (5.4% in the PD group vs. 2.5% in the
      non-PD group, p=0.1). All individual components of TLR, death, and MI were
      similar as well as definite/probable scaffold thrombosis between the two groups.
      CONCLUSIONS: These results reflect very similar final angiographic and clinical
      results achieved with or without post-dilation in the treatment of low to
      moderately complex coronary lesions. Therefore, post-dilation should be performed
      whenever needed to optimise acute results.

PMID- 25982922
TI  - Short-Term Effect of Estrogen on Human Bone Marrow Fat.
AB  - Bone marrow fat, an unique component of the bone marrow cavity increases with
      aging and menopause and is inversely related to bone mass. Sex steroids may be
      involved in the regulation of bone marrow fat, because men have higher bone
      marrow fat than women and clinical observations have suggested that the variation
      in bone marrow fat fraction is greater in premenopausal compared to
      postmenopausal women and men. We hypothesized that the menstrual cycle and/or
      estrogen affects the bone marrow fat fraction. First, we measured vertebral bone
      marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a
      week during 1 month in 10 regularly ovulating women. The vertebral bone marrow
      fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p
      = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, -0.01 to 0.04)
      during the luteal phase (p = 0.091). To determine the effect of estrogen on bone
      marrow fat, we measured vertebral bone marrow fat fraction every week for 6
      consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of
      oral 17-beta estradiol treatment (2 mg/day). Bone marrow fat fraction decreased
      by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI,
      0.34 to 0.51) during 17-beta estradiol administration (p < 0.001) and increased
      again after cessation. During 17-beta estradiol administration the bone formation
      marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone
      resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx)
      decreased (p < 0.001). In conclusion, we described the variation in vertebral
      bone marrow fat fraction among ovulating premenopausal women. And among
      postmenopausal women, we demonstrated that 17-beta estradiol rapidly reduces the
      marrow fat fraction, suggesting that 17-beta estradiol regulates bone marrow fat
      independent of bone mass.

PMID- 25982923
TI  - Influence of biofilms on heavy metal immobilization in sustainable urban drainage
      systems (SuDS).
AB  - This paper physically and numerically models the influence of biofilms on heavy
      metal removal in a gravel filter. Experimental flow columns were constructed to
      determine the removal of Cu, Pb and Zn by gabbro and dolomite gravel lithologies
      with and without natural biofilm from sustainable urban drainage systems (SuDS).
      Breakthrough experiments showed that, whilst abiotic gravel filters removed up to
      51% of metals, those with biofilms enhanced heavy metal removal by up to a
      further 29%, with Cu removal illustrating the greatest response to biofilm
      growth. An advection-diffusion equation successfully modelled metal tracer
      transport within biofilm columns. This model yielded a permanent loss term (k)
      for metal tracers of between 0.01 and 1.05, correlating well with measured data
      from breakthrough experiments. Additional 16S rRNA clone library analysis of the
      biofilm indicated strong sensitivity of bacterial community composition to the
      lithology of the filter medium, with gabbro filters displaying Proteobacteria
      dominance (54%) and dolomite columns showing Cyanobacteria dominance (47%). 

PMID- 25982924
TI  - Metal-free C(3)-H arylation of coumarins promoted by catalytic amounts of
      5,10,15,20-tetrakis(4-diethylaminophenyl)porphyrin.
AB  - The metal-free C-H arylation of coumarins was achieved in the presence of
      catalytic amounts of 5,10,15,20-tetrakis(4-diethylaminophenyl)porphyrin. This
      mild and environmentally friendly Meerwein arylation provided facile access to a
      broad variety of 3-arylcoumarins in synthetically useful yields. 

PMID- 25982925
TI  - A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine.
AB  - Neurodegenerative disorders are one of the leading causes of death among the
      elderly. Therapeutic approaches with a single target have proven unsuccessful in
      treating these diseases. Structural combination of multi-functional compounds may
      lead to a molecule with multiple properties. In this study, we designed and
      synthesized T-006, a novel analog derived from two multi-functional
      neuroprotective chemicals, tetramethylpyrazine and J147. The methoxyphenyl group
      of J147 was replaced by tetramethylpyrazine. Bioactivity evaluation showed that T
      006 at very low concentrations had multi-functional neuroprotective effects
      including rescuing iodoacetic acid-induced neuronal loss, preventing oxidative
      stress-induced neurotoxicity and reducing glutamate-induced excitotoxicity in
      vitro. Most importantly, T-006 significantly ameliorated memory impairments in
      APP/PS1 transgenic mice. These multiple functions of a single molecule suggest
      that T-006 is a promising novel neuroprotective agent for treating various
      neurodegenerative disorders, including and in particular Alzheimer's disease. 

PMID- 25982927
TI  - Healthy Eating and Barriers Related to Social Class. The case of vegetable and
      fish consumption in Norway.
AB  - The article examines the constraints on healthy eating by exploring whether
      barriers such as taste, competence, time, price, quality and limited selection
      reduce consumption of vegetables and fish among Norwegians. In order to
      understand the socio-economic gradient of healthy diets, the study examines how
      these barriers are related to specific class positions. Regular consumption of
      both fish and vegetables are recommended by health authorities, and they are
      broadly perceived as healthy foods by Norwegians. Nevertheless, more than half of
      the population consumes vegetables less frequently than daily, and the average
      consumption of fish is far below the recommended two to three dinner portions of
      fish on a weekly basis. Informed by Bourdieu's theories of social class, this
      article argues for two overarching barriers related to food consumption, food
      knowledge and perceived food quality by consumers, and it finds that barriers are
      tied to scarcity of cultural, economic and social capital. A survey of 2000
      respondents subjected to multiple linear regression analysis and factor analysis
      (PCA) provides the evidence for this study. 

PMID- 25982926
TI  - Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin
      Proteinase Inhibitors in Parkinson's Disease.
AB  - Neuroinflammation is thought to contribute to cell death in neurodegenerative
      disorders, but the factors involved in the inflammatory process are not
      completely understood. Proteinase-activated receptor-2 (PAR2) expression in brain
      is increased in Alzheimer's disease and multiple sclerosis, but the status of
      PAR2 in Parkinson's disease is unknown. This study examined expression of PAR2
      and endogenous proteinase activators (trypsin-2, mast cell tryptase) and
      proteinase inhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistant
      to neurodegeneration in Parkinson's disease at different Braak alpha-synuclein
      stages of the disease in post-mortem brain. In normal aged brain, expression of
      PAR-2, trypsin-2, and serpin-A5 and serpin-A13 was found in neurons and
      microglia, and alterations in the amount of immunoreactivity for these proteins
      were found in some brain regions. Namely, there was a decrease in neurons
      positive for serpin-A5 in the dorsal motor nucleus, and serpin-A13 expression was
      reduced in the locus coeruleus and primary motor cortex, while expression of
      PAR2, trypsin-2 and both serpins was reduced in neurons within the substantia
      nigra. There was an increased number of microglia that expressed serpin-A5 in the
      dorsal motor nucleus of vagus and elevated numbers of microglia that expressed
      serpin-A13 in the substantia nigra of late Parkinson's disease cases. The number
      of microglia that expressed trypsin-2 increased in primary motor cortex of
      incidental Lewy body disease cases. Analysis of Parkinson's disease cases alone
      indicated that serpin-A5 and serpin-A13, and trypsin-2 expression in midbrain and
      cerebral cortex was different in cases with a high incidence of L-DOPA-induced
      dyskinesia and psychosis compared to those with low levels of these treatment
      induced side effects. This study showed that there was altered expression in
      brain of PAR2 and some proteins that can control its function in Parkinson's
      disease. Given the role of PAR2 in neuroinflammation, drugs that mitigate these
      changes may be neuroprotective when administered to patients with Parkinson's
      disease. 

PMID- 25982928
TI  - Managing young children's snack food intake. The role of parenting style and
      feeding strategies.
AB  - One major contributor to the problem of childhood overweight and obesity is the
      over-consumption of foods high in fat, salt and sugar, such as snack foods. The
      current study aimed to examine young children's snack intake and the influence of
      feeding strategies used by parents in the context of general parenting style.
      Participants were 611 mothers of children aged 2-7 years who completed an online
      questionnaire containing measures of general parenting domains and two particular
      feeding strategies, restriction and covert control. It was found that greater
      unhealthy snack intake was associated with higher restriction and lower covert
      control, while greater healthy snack intake was associated with lower restriction
      and higher covert control. Further, the feeding strategies mediated the
      association between parental demandingness and responsiveness and child snack
      intake. These findings provide evidence for the differential impact of
      controlling and positive parental feeding strategies on young children's snack
      intake in the context of general parenting. 

PMID- 25982929
TI  - A low incidence of iodine-induced hyperthyroidism following administration of
      iodinated contrast in an iodine-deficient region.
AB  - OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced
      thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study
      was to determine the incidence of iodinated contrast-induced thyrotoxicosis and
      to determine whether thyrotoxicosis was more common in patients >=70 years
      compared to those <70 years of age. DESIGN: A prospective study of adult patients
      undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS:
      Thyroid function tests (TFTs) and urine iodine measurements were performed prior
      to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from
      baseline were analysed. RESULTS: A total of 102 patients were included in the
      final analysis. Overall, TSH levels dropped (P = 0.0002), and free T3 (FT3 )
      levels increased (P = 0.04) between baseline and week 4 with normalization by
      week 8; however, these changes were not considered clinically significant. No
      significant differences in free T4 (FT4 ) occurred in the overall group (P =
      0.82). There were no differences in TFTs between baseline and 4 or 8 weeks for
      those patients aged <70 compared to >=70 years. Two patients developed new
      subnormal TSH values. Of these, one had a 90-mm follicular variant papillary
      thyroid carcinoma diagnosed while the other had a normal thyroid assessment and
      TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients
      developed subclinical hyperthyroidism following a standard dose of iodinated
      contrast for CT investigations. Given the low incidence of iodine-induced
      thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid
      function testing in our region.

PMID- 25982930
TI  - Moh Daha, the organizer.

PMID- 25982931
TI  - Redesigned Escherichia coli cytosine deaminase: a new facet of suicide gene
      therapy.
AB  - BACKGROUND: The Escherichia coli cytosine deaminase (CD)/5-fluorocytosine (5-FC)
      approach emerges as a potential aid for suicide gene therapy in the field of
      modern cancer treatment. However, the poor binding affinity of CD towards 5-FC
      compared to the natural substrate cytosine limits its application for successful
      suicide gene therapy. Redesigning a bacterial mutant CD with site-directed
      mutagenesis showed higher potency compare to wild-type CD (wtCD) in vitro. In the
      present study, we conducted a comparative analysis of F186W mutant and wtCD in a
      human lung cancer cell line (A549). METHODS AND RESULTS: A comparative
      investigation was initiated with cell viability analyses by MTT and trypan blue
      dye exclusion assays on A549 cells transfected with wtCD and F186W genes. The
      mode of cell death was confirmed by acridine Orange/ethidium Bromide dual
      staining. Furthermore, flow cytometric assessments were performed by cell cycle
      analysis and caspase 3 assay. The experimental results showed a drug dependent
      decrease in cell viability; interestingly, mutant (F186W) reached IC50 at a much
      lower concentration of prodrug (5-FC) than wtCD. Cell cycle analysis showed that
      G1 arrest of a larger population of 5-FC treated F186W transfected cells, in
      contrast to that of wtCD under similar conditions. The caspase 3 assay revealed
      progression and execution of apoptosis. CONCLUSIONS: We report a novel bacterial
      CD mutant that provided a superior alternate to the wtCD suicide gene. The F186W
      mutant required a much lower dose of 5-FC to reach its IC50 , thus minimizing the
      systemic side effects of large doses of 5-FC as required for wtCD.

PMID- 25982932
TI  - Ketamine and suicidal ideation in depression: Jumping the gun?
AB  - Depression and suicide are known to be intricately entwined but the
      neurobiological basis underlying this association is yet to be understood.
      Ketamine is an N-methyl d-aspartate (NMDA) receptor antagonist used for induction
      and maintenance of general anaesthesia but paradoxically its euphoric effects
      lead to its classification under drugs of abuse. The serendipitous finding of
      rapid-onset antidepressant action of subanaesthetic dosing with ketamine by
      intravenous infusion has sparked many preclinical and clinical investigations. A
      remarkable suppression of suicidal ideation was also reported in depressed
      patients. This review focuses on the clinical trials on ketamine that reported
      remedial effects in suicidal ideation in depression and addresses also the
      molecular mechanisms underlying the antidepressant and psychotomimetic actions of
      ketamine. The neuropsychiatric profile of subanaesthetic doses of ketamine
      encourages its use in the management of suicidal ideation that could avert
      emergent self-harm or suicide. Finally, the need for neuroimaging studies in
      suicidal patients to identify the brain region specific and temporal effects of
      ketamine, and the possibility of employing ketamine as an experimental tool in
      rodent-based studies to study the mechanisms underlying suicidal behaviour are
      highlighted. 

PMID- 25982933
TI  - Kaempferol and inflammation: From chemistry to medicine.
AB  - Inflammation is an important process of human healing response, wherein the
      tissues respond to injuries induced by many agents including pathogens. It is
      characterized by pain, redness and heat in the injured tissues. Chronic
      inflammation seems to be associated with different types of diseases such as
      arthritis, allergies, atherosclerosis, and even cancer. In recent years natural
      product based drugs are considered as the novel therapeutic strategy for
      prevention and treatment of inflammatory diseases. Among the different types of
      phyto-constituents present in natural products, flavonoids which occur in many
      vegetable foods and herbal medicines are considered as the most active
      constituent, which has the potency to ameliorate inflammation under both in vitro
      and in vivo conditions. Kaempferol is a natural flavonol present in different
      plant species, which has been described to possess potent anti-inflammatory
      properties. Despite the voluminous literature on the anti-inflammatory effects of
      kaempferol, only very limited review articles has been published on this topic.
      Hence the present review is aimed to provide a critical overview on the anti
      inflammatory effects and the mechanisms of action of kaempferol, based on the
      current scientific literature. In addition, emphasis is also given on the
      chemistry, natural sources, bioavailability and toxicity of kaempferol. 

PMID- 25982934
TI  - Catecholate siderophore esterases Fes, IroD and IroE are required for
      salmochelins secretion following utilization, but only IroD contributes to
      virulence of extra-intestinal pathogenic Escherichia coli.
AB  - Salmochelins are glucosylated forms of enterobactin (enterochelin) and contribute
      to the virulence of Salmonella enterica and some extra-intestinal pathogenic
      Escherichia coli (ExPEC). Fes, IroD and IroE esterases degrade salmochelins and
      enterobactin to release iron. We investigated the apparently redundant role of
      these esterases in virulence and in salmochelin production and utilization of the
      ExPEC strain chi7122. The DeltairoD, DeltafesDeltairoD and
      DeltafesDeltairoDDeltairoE mutants displayed attenuated virulence phenotypes in
      an avian systemic infection model. Growth of DeltafesDeltairoD and
      DeltafesDeltairoDDeltairoE mutants was severely reduced in the presence of
      conalbumin, and although enterobactin was produced, no salmochelins were detected
      in the culture supernatants of these mutants. Elimination of catecholate
      synthesis via an entA deletion in a DeltafesDeltairoDDeltairoE restored growth in
      the presence of conalbumin, but only partially restored the virulence of the
      strain. Salmochelin production was reestablished by reintroducing active
      esterases. Intracellular accumulation of cyclic mono-glucosylated enterobactin
      was observed in the triple mutant DeltafesDeltairoDDeltairoE, and deletion of
      fepC, required for catecholate import into the cytoplasm, restored salmochelin
      detection in supernatants. These results suggest that in the absence of
      esterases, cyclic salmochelins are synthesized and secreted, but remain cell
      bound after internalization indicating that esterase-mediated degradation is
      required for re-secretion of catecholate siderophore molecules following their
      utilization. 

PMID- 25982935
TI  - Silver nanoparticles decorated anatase TiO22nanotubes for removal of
      pentachlorophenol from water.
AB  - One-dimensional nanotubes are promising materials for environmental applications.
      In this study, anatase TiO2 nanotubes (TNTs) were fabricated using an alkaline
      hydrothermal method at 130 degrees C and then calcinated at 400 degrees C for 2h.
      Ag nanoparticles were photo-deposited onto the TNTs for enhanced photodegradation
      of pentachlorophenol (PCP) under simulated solar light. The samples were
      characterized using transmission electron microscopy, physical adsorption of
      nitrogen, X-ray diffraction, X-ray photoelectron spectroscopy and UV-Visible
      diffuse reflectance spectroscopic techniques. The as-synthesized TNTs showed
      tubular structures with the outer and inner diameter of 9-10 and 5-6 nm,
      respectively. The results showed that metallic Ag nanoparticles were uniformly
      dispersed on the TNTs surface, and Ag/TNTs exhibited significant visible-light
      absorption. After 180 min irradiation, about 99% PCP was removed by Ag/TNTs (5.4
      at.%), compared to 54.3% by P25 and 59.4% by pure TNTs. This is attributed to the
      synergistic effects between Ag nanoparticles acting as traps to effectively
      capture the photo-generated electrons, and the localized surface plasmon
      resonance (LSPR) of Ag nanoparticles promoting the absorption of visible light.
      The intermediates during the PCP photodegradation were systematically analyzed,
      ruling out the existence of high toxic polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans. Ag/TNTs showed excellent stability even after five
      cycles.

PMID- 25982936
TI  - Efficient arsenic(V) and arsenic(III) removal from acidic solutions with Novel
      Forager Sponge-loaded superparamagnetic iron oxide nanoparticles.
AB  - Nowadays, there is a wide variety of arsenic decontamination processes being
      adsorption processes the most efficient. In this concern, superparamagnetic iron
      oxide nanoparticles (SPION) have been proposed as an appropriate system to
      improve arsenic adsorption from acidic wastewater. The number of mines, the
      amount of ore processed, and thus the amount of mine (acid) wastewaters have been
      rapidly increased in recent decades. For this reason, arsenic removal from
      contaminated water is an important goal to accomplish environmental regulations.
      It is noteworthy that aggregation of these nanoparticles has been detected as the
      main difficulty, hindering the promising adsorption. In order to overcome this
      drawback, it is proposed a system to avoid aggregation based on nanoparticles
      dispersion into an appropriate supporting material. To this purpose, SPION have
      been fixed on a cellulosic sponge achieving a decrease of the aggregation state,
      an increase of the active centers, and consequently, arsenic adsorption
      increases. Experimental results report a lower aggregation of supported SPION
      over sponge than the observed in the non supported nanoparticles. At this point,
      a remarkable improvement in the sponge system adsorption capacity is observed in
      comparison with superparamagnetic nanoparticles in suspension, reaching
      adsorption capacities about 2.1 mmol As/g SPION and 12.1 mmol As/g SPION for
      arsenite and arsenate, respectively at pH 3.8. Then, the developed system not
      only amends the aggregation problem but also keep their nanoproperties intact,
      making the system a suitable one for arsenic removal in acidic wastewater
      treatment.

PMID- 25982937
TI  - Anisotropic wetting properties on various shape of parallel grooved
      microstructure.
AB  - It has been revealed experimentally that some superhydrophobic surfaces in
      nature, such as rice leaf, show strong anisotropic wetting behavior. In this
      work, based on a thermodynamic approach, the effects of profile shape of parallel
      grooved microstructure on free energy (FE) with its barrier (FEB) and equilibrium
      contact angle (ECA) with its hysteresis (CAH) for various orientations of
      different parallel micro texture surface have been systematically investigated in
      detail. The results indicated that the anisotropy of wetting properties strongly
      depended on the specific topographical features and wetting state. In particular,
      a paraboloidal profile of parallel micro-texture surface is used as an important
      example to theoretically establish the relationship between surface geometry and
      anisotropic wetting behavior for optimal design, showing that the wetting
      behavior of the composite state is similar to that of the non-composite state and
      the anisotropy will possibly be appeared with the decrease of height or intrinsic
      contact angle of paraboloidal profile of micro texture. 

PMID- 25982938
TI  - Atom transfer radical polymerization to fabricate monodisperse poly[glycidyl
      methacrylate-co-poly (ethylene glycol) methacrylate] microspheres and its
      application for protein affinity purification.
AB  - Poly[glycidyl methacrylate-co-poly (ethylene glycol) methacrylate] microspheres
      for the first time were successfully synthesized by atom transfer radical
      polymerization (ATRP) method at room temperature. The co-polymerization approach
      was investigated to delicately control the microsphere morphology and size
      distribution by reaction conditions including solvent percentage, monomer loading
      and rotation speed. The results show that the average size of the microspheres is
      ~5.7 MUm with coexistence of epoxy, hydroxyl and ether groups, which provide
      plentiful functional sites for protein anchoring. The mechanism of the
      microsphere formation is proposed. The microsphere successfully demonstrates its
      unique application for affinity purification of proteins, in which the functional
      epoxy group facilitates a simple and efficient protein covalent immobilization to
      purify immunoglobulin G on the microspheres, while the hydrophilic poly (ethylene
      glycol) motif can repulse nonspecific protein adsorption for good specificity.
      This microspheres can be used in broad protein biosensors due to their abundant
      functional groups and high surface to volume ratio.

PMID- 25982939
TI  - Has neonatal dialysis become morally obligatory? Lessons from Baby Doe.

PMID- 25982940
TI  - White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria.
AB  - l-2-Hydroxyglutaric aciduria (l-2-HGA) is a rare inborn error of metabolism.
      Mainly, patients with this disorder exhibit neurological symptoms and
      characteristic neuroradiological findings, such as subcortical white matter
      abnormalities, which are believed to be caused by the toxicity of the
      accumulation of l-2-hydroxyglutaric acid. A genotype-first approach of the whole
      exome sequence was used to identify compound heterozygous mutations, c.584A>G
      (p.Y195C) and c.772T>C (p.C258R), in L2HGDH, the gene responsible for this
      disorder, in an adult patient with intellectual disability and intractable
      epilepsy. A retrospective assay confirmed the increased concentrations of 2
      hydroxyglutaric acid in the urine. These results suggested that neuroradiological
      findings of subcortical white matter abnormalities are characteristic of l-2-HGA
      and that clinical exome sequencing has sufficient power to compensate for
      insufficient clinical evaluations. 

PMID- 25982941
TI  - Pituitary tumor risk in relation to mobile phone use: A case-control study.
AB  - BACKGROUND: The number of mobile phone users has grown rapidly, which has
      generated mounting public concern regarding possible health hazards. This study
      aims to assess pituitary tumor risk, as it has rarely been investigated. MATERIAL
      AND METHODS: A case-control study was conducted with 80 eligible cases identified
      from all five university hospitals in Finland and frequency-matched 240 controls
      from the national population register. Controls were matched to cases by age,
      sex, region of residence and date of interview. A detailed history of mobile
      phone use was obtained using a structured interview. Several indicators of mobile
      phone use were assessed using conditional logistic regression. RESULTS: A reduced
      odds ratio was seen among regular mobile phone users [OR 0.39, 95% confidence
      interval (CI) 0.21, 0.72] relative to never/non-regular users, possibly
      reflecting methodological limitations. Pituitary tumor risk was not increased
      after 10 or more years since first use (OR 0.69, 95% CI 0.25, 1.89). The risk was
      not increased in relation to duration, cumulative hours of use, or cumulative
      number of calls. The results were similar for analog and digital phones.
      CONCLUSIONS: We found no excess risk associated with self-reported short- or
      medium-term use of mobile phones. This is consistent with most of the published
      studies. However, uncertainties remained for longer duration of use, as a very
      small proportion of study participants reported use beyond 10 years.

PMID- 25982942
TI  - Curcumin alleviates cisplatin-induced learning and memory impairments.
AB  - The present study has been designed to investigate the role of curcumin on
      cisplatin-inducedcognitive impairment and to reveal mechanisms of cisplatin's
      detrimental actions on cognition in rats. Animals were treated with cisplatin
      (5mg/kg/week) and/or curcumin (300mg/kg/day) for 5weeks. Morris water maze test
      was used to assess spatial learning and memory. Enzymatic activities of
      acetylcholinesterase (AChE) and superoxide dismutase (SOD) were evaluated from
      hippocampus and plasma samples, and malondialdehyde (MDA), which is the end
      product of lipid peroxidation, was determined by a colorimetric method. Our
      results showed that cisplatin (5mg/kg/week, 5weeks) caused learning and memory
      deficits, elevated MDA content, decreased SOD activity in the hippocampus and
      plasma, and AChE activity in the hippocampus. Curcumin improved learning and
      memory in rats with administration of cisplatin. In addition, curcumin
      significantly reduced the level of MDA and increased the activities of SOD and
      AChE. Taken together, our findings indicate that curcumin ameliorates cisplatin
      induced spatial learning and memory impairment, possibly through restored
      cholinergic function and enhanced oxidative status. 

PMID- 25982943
TI  - High trait anxiety during adolescence interferes with discriminatory context
      learning.
AB  - Persistent adult anxiety disorders often begin in adolescence. As emphasis on
      early treatment grows, we need a better understanding of how adolescent anxiety
      develops. In the current study, we used a fear conditioning paradigm to identify
      disruptions in cue and context threat-learning in 19 high anxious (HA) and 24 low
      anxious (LA) adolescents (12-17years). We presented three neutral female faces
      (conditioned stimulus, CS) in three contingent relations with an unconditioned
      stimulus (UCS, a shrieking female scream) in three virtual room contexts. The
      degree of contingency between the CSs and the UCSs varied across the rooms: in
      the predictable scream condition, the scream followed the face on 100% of trials;
      in the unpredictable scream condition, the scream and face appeared randomly and
      independently of each other; in the no-scream condition the CS was presented in
      the absence of any UCS. We found that the LA adolescents showed higher levels of
      fear-potentiated startle to the faces relative to the rooms. This difference was
      independent of the contingency condition. The HA adolescents showed non
      differential startle between the CSs, but, in contrast to previous adult data,
      across both cue types displayed lowest startle to the unpredictable condition and
      highest startle to the no-scream condition. Our study is the first to examine
      context conditioning in adolescents, and our results suggest that high trait
      anxiety early in development may be associated with an inability to disambiguate
      the signalling roles of cues and contexts, and a mislabelling of safety or
      ambiguous signals. 

PMID- 25982944
TI  - Transgene expression in Penaeus monodon cells: evaluation of recombinant
      baculoviral vectors with shrimp specific hybrid promoters.
AB  - It has been realized that shrimp cell immortalization may not be accomplished
      without in vitro transformation by expressing immortalizing gene in cells. In
      this process, efficiency of transgene expression is confined to the ability of
      vectors to transmit gene of interests to the genome. Over the years,
      unavailability of such vectors has been hampering application of such a strategy
      in shrimp cells. We report the use of recombinant baculovirus mediated
      transduction using hybrid promoter system for transgene expression in lymphoid
      cells of Penaeus monodon. Two recombinant baculovirus vectors with shrimp viral
      promoters (WSSV-Ie1 and IHHNV-P2) were constructed (BacIe1-GFP and BacP2-GFP) and
      green fluorescent protein (GFP) used as the transgene. The GFP expression in
      cells under the control of hybrid promoters, PH-Ie1 or PH-P2, were analyzed and
      confirmed in shrimp cells. The results indicate that the recombinant baculovirus
      with shrimp specific viral promoters (hybrid) can be employed for delivery of
      foreign genes to shrimp cells for in vitro transformation. 

PMID- 25982946
TI  - Leishmania donovani influenced cytokines and Toll-like receptors expression among
      Sudanese visceral leishmaniasis patients.
AB  - Leishmaniasis remains a serious health problem. The outcome of Leishmania
      infection depends on the early innate response. In this study, whole blood
      samples of 40 patients with visceral leishmaniasis (VL), 10 leishmanin skin test
      negative (LST-ve) controls and 10 leishmanin skin test-positive (LST+ve) controls
      were stimulated by live L. donovani promastigotes. Also, THP1 human cell line was
      infected with L. donovani. The production of interleukin 10 (IL-10), tumour
      necrosis factor alpha (TNF) and interferon gamma (IFNG) cytokines was measured,
      and the expression of Toll-like receptors (TLR2, TLR4 and TLR9) was done in the
      blood samples and also in the THP1 cell line. IL-10 was found to be higher in
      LST+ve controls compared with VL patients. TNF was moderately produced with no
      variation between patients, controls and THP1 cells. IFNG was higher in LST+ve
      controls also in THP1 cells. TLR4 and TLR9 were found to be highly expressed in
      patients with VL. L. donovani increases the expression of TLR4 and TLR9 in
      patients with VL and TLR2 in THP1 cells, suggesting a TLRs relation in induction
      of a mixed cytokine response. TLR9 was markedly recognized by L. donovani DNA.

PMID- 25982945
TI  - Conformational Changes of the Clamp of the Protein Translocation ATPase SecA.
AB  - Post-translational protein translocation across the bacterial plasma membrane is
      mediated by the interplay of the SecA ATPase and the protein-conducting SecY
      channel. SecA consists of several domains, including two nucleotide-binding
      domains (NBD1 and NBD2), a polypeptide cross-linking domain (PPXD), a helical
      scaffold domain (HSD), and a helical wing domain (HWD). PPXD, HSD, and NBD2 form
      a clamp that positions the polypeptide substrate above the channel so that it can
      be pushed into the channel by a two-helix finger of the HSD. How the substrate is
      accommodated in the clamp during translocation is unclear. Here, we report a
      crystal structure of Thermotoga maritima SecA at 1.9 A resolution. Structural
      analysis and free-energy calculations indicate that the new structure represents
      an intermediate state during the transition of the clamp from an open to a closed
      conformation. Molecular dynamics simulations show that closure of the clamp
      occurs in two phases, an initial movement of PPXD, HSD, and HWD as a unit,
      followed by a movement of PPXD alone toward NBD2. Simulations in the presence of
      a polypeptide chain show that the substrate associates with the back of the clamp
      by dynamic hydrogen bonding and that the clamp is laterally closed by a conserved
      loop of the PPXD. Mutational disruption of clamp opening or closure abolishes
      protein translocation. These results suggest how conformational changes of SecA
      allow substrate binding and movement during protein translocation.

PMID- 25982947
TI  - Consequence of climate mitigation on the risk of hunger.
AB  - Climate change and mitigation measures have three major impacts on food
      consumption and the risk of hunger: (1) changes in crop yields caused by climate
      change; (2) competition for land between food crops and energy crops driven by
      the use of bioenergy; and (3) costs associated with mitigation measures taken to
      meet an emissions reduction target that keeps the global average temperature
      increase to 2  degrees C. In this study, we combined a global computable general
      equilibrium model and a crop model (M-GAEZ), and we quantified the three impacts
      on risk of hunger through 2050 based on the uncertainty range associated with 12
      climate models and one economic and demographic scenario. The strong mitigation
      measures aimed at attaining the 2  degrees C target reduce the negative effects
      of climate change on yields but have large negative impacts on the risk of hunger
      due to mitigation costs in the low-income countries. We also found that in a
      strongly carbon-constrained world, the change in food consumption resulting from
      mitigation measures depends more strongly on the change in incomes than the
      change in food prices.

PMID- 25982948
TI  - Differentials in vitamin A supplementation among preschool-aged children in
      Ethiopia: evidence from the 2011 Ethiopian Demographic and Health Survey.
AB  - BACKGROUND: Vitamin A supplementation is one of the best proven, safest and most
      cost-effective interventions in public health. However, childhood vitamin A
      supplementation has not reached adequate levels of coverage in developing
      countries. This study aimed to identify factors associated with childhood vitamin
      A supplementation in Ethiopia. STUDY DESIGN: Cross-sectional study with
      stratified, two-stage cluster design. METHODS: Analysis of data from the 2011
      Ethiopian Demographic and Health Survey (EDHS) was used to identify factors
      associated with childhood vitamin A supplementation. Data for 9276 children aged
      6-59 months were included in the analysis. Binary and multivariable logistic
      regression models were used. RESULTS: Over half [54.5%, 95% confidence interval
      (CI) 53.48-55.51%] of children aged 6-59 months had received vitamin A
      supplementation in the last six months. Regional differences were found, ranging
      from 28.1% in Somali to 83.2% in Tigray (P < 0.001). Children in the poorest
      wealth index category [adjusted odds ratio (AOR) 0.60, 95% CI 0.47-0.77],
      children with mothers who did not attend any antenatal care (ANC) appointments
      (AOR 0.56, 95% CI 0.48-0.67), infants aged 6-11 months (AOR 0.52, 95% CI 0.42
      0.65), children with mothers who did not have a postnatal medical check-up (AOR
      0.69, 95% CI 0.56-0.86) and children with mothers who had not worked in the last
      year (AOR 0.86, 95% CI 0.76-0.97) were less likely to have received vitamin A
      supplementation in the last six months. CONCLUSION: Coverage of childhood vitamin
      A supplementation was not optimum in Ethiopia and regional differences were
      found. Lack of a maternal postnatal medical check-up, lack of ANC attendance,
      poorest wealth index, mother who had not worked in the last year and infant in
      youngest age group were associated with lower odds of receiving vitamin A
      supplementation over the last six months. Provision and promotion of ANC and
      postnatal care, and strengthening routine immunization activity, especially among
      infants in the youngest age group, are recommended to increase coverage of
      childhood vitamin A supplementation.

PMID- 25982949
TI  - Molecular signals required for the establishment and maintenance of
      ectomycorrhizal symbioses.
AB  - Ectomycorrhizal (ECM) symbioses are among the most widespread associations
      between roots of woody plants and soil fungi in forest ecosystems. These
      associations contribute significantly to the sustainability and sustainagility of
      these ecosystems through nutrient cycling and carbon sequestration.
      Unfortunately, the molecular mechanisms controlling the mutual recognition
      between both partners are still poorly understood. Elegant work has demonstrated
      that effector proteins from ECM and arbuscular mycorrhizal (AM) fungi regulate
      host defenses by manipulating plant hormonal pathways. In parallel, genetic and
      evolutionary studies in legumes showed that a 'common symbiosis pathway' is
      required for the establishment of the ancient AM symbiosis and has been recruited
      for the rhizobia-legume association. Given that genes of this pathway are present
      in many angiosperm trees that develop ectomycorrhizas, we propose their potential
      involvement in some but not all ECM associations. The maintenance of a successful
      long-term relationship seems strongly regulated by resource allocation between
      symbiotic partners, suggesting that nutrients themselves may serve as signals.
      This review summarizes our current knowledge on the early and late signal
      exchanges between woody plants and ECM fungi, and we suggest future directions
      for decoding the molecular basis of the underground dance between trees and their
      favorite fungal partners. 

PMID- 25982950
TI  - Fluorescence Quenching of Perylene DBPI Dye by Colloidal Low-Dimensional Gold
      Nanoparticles.
AB  - The interaction of a perylene DBPI dye [N,N-bis(2,5-di-tert-butylphenyl)-3,4:9,10
      perylenebis(dicarboximide)] with aqueous colloidal gold nanoparticles (AuNPs) was
      studied using steady state fluorescence quenching measurements. The Stern-Volmer
      quenching rate constant (Ksv) was calculated as ~2.2 * 10(8) and ~1.072 * 10(9)
      M(-1) in ethanol and ethylene glycol respectively. From fluorescence quenching
      data, the static quenching and energy transfer play a significant role in the
      fluorescence quenching of DBPI with AuNPs. The apparent association constant
      (Kapp) was calculated as ~1.4 * 10(9) (EtOH)and ~3.7 * 10(9) M(-1) (ethylene).
      Due to AuNPs interaction with DBPI, the average aggregated colloidal AuNPs size
      is increased from ~53.39 nm (before interaction) to ~94.12 nm (after
      interaction).

PMID- 25982951
TI  - Carbon tetrachloride-induced liver injury in mice is tissue factor dependent.
AB  - Tissue factor (TF) is a membranous glycoprotein that activates the coagulation
      system when blood vessels or tissues are damaged. TF was up-regulated in
      monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. The present
      study aimed to test the hypothesis that TF-dependent fibrin deposition occurs in
      liver toxicity induced by CCl4 in mice. Pericentral deposition of TF and fibrin
      is induced after CCl4-induced liver toxicity. The toxicity was evaluated by
      determination of serum activities of ALT, AST and ALP as well as GSH content and
      histopathological changes. The results showed that injection of mice with TF
      antisense deoxyoligonucleotide (TF-AS) prevented the accumulation of TF and
      fibrin in the hepatic tissues. Furthermore, it significantly restored blood
      biochemical parameters, GSH content and distorted histopathological features
      caused by CCl4. The current study demonstrates that TF activation is associated
      with CCl4-induced liver injury. Furthermore, administration of TF-AS successfully
      prevented this type of liver injury. 

PMID- 25982952
TI  - More than little old women....

PMID- 25982953
TI  - Inhibitory effect of quercetin in the formation of advance glycation end products
      of human serum albumin: An in vitro and molecular interaction study.
AB  - Non-enzymatic glycation entails the reaction between the carbonyl group of a
      sugar with the amino group of a protein giving rise to Schiff base and Amadori
      products. The formation of advanced glycation end products (AGEs) leads to the
      generation of free radicals, which play an important role in the pathophysiology
      of ageing and diabetes. Bioavailable dietary antioxidants like quercetin (QC) are
      thought to inhibit AGEs formation. This study was aimed to investigate the effect
      of quercetin on AGE formation and features the glycation of human serum albumin
      (HSA) and its characterization by various spectroscopic techniques. The effect of
      quercetin, against the formation of AGEs was studied using a glycated human serum
      albumin product, haemoglobin-delta-gluconolactone, and aminoguanidine. The
      results were then corroborated with estimation of protein oxidation, lipid
      peroxidation and comet assay. On the basis of the experimental data,
      computational docking studies were then performed to understand the location of
      the site of quercetin binding and its best bound conformation with respect to
      human serum albumin. Through this study we have demonstrated the mechanism of
      formation of AGE and its inhibition by quercetin. We have also suggested that the
      supplementation with dietary antioxidants like quercetin might protect against
      free radical toxicity. 

PMID- 25982954
TI  - Biocompatibility of biomimetic multilayered alginate-chitosan/beta-TCP scaffold
      for osteochondral tissue.
AB  - Biomimetic three-layered monolithic scaffold (TLS) intended for treatment of
      osteochondral defects was fabricated by using freeze drying method. The
      multilayered material was prepared with chitosan (C) and alginate (A)
      polyelectrolyte complex (CA/PEC) as a cartilaginous layer, a combination of
      CA/PEC (60 wt%) and beta-tricalcium phosphate (beta-TCP) (40 wt%) as an
      intermediate layer and a combination of CA/PEC (30 wt%) and beta-TCP (70 wt%) as
      a subchondral layer in order to mimic the inherent gradient structure of healthy
      osteochondral tissue. Characterization of the scaffolds was performed using
      Fourier transform infrared (FT-IR) spectroscopy analysis, swelling and scanning
      electron microscopy (SEM) tests. In vitro cytotoxicity assay with L929 cells and
      EpiDerm skin irritation test (SIT) using the EpiDerm reconstructed human
      epidermal (RHE) model were performed to analyze biocompatibility of the
      scaffolds. Characterization results showed that there were strong ionic
      interactions among chitosan, alginate and beta-TCP and the layers showed
      interconnected porous structure with different swelling ratios. The relative cell
      viability and SIT results were greater than 70% indicating that the scaffolds are
      considered nontoxic according to the International Organization for
      Standardization (ISO) standard. All results taken together, biomimetic TLS can be
      considered to be suitable for osteochondral applications.

PMID- 25982955
TI  - Capillary electrophoretic methods applied to the investigation of peptide
      complexes.
AB  - This article gives an overview of the applications of capillary electrophoretic
      methods to investigate the non-covalent interactions of peptides (peptide
      complexes) with variable middle- and high-molecular-mass receptors (ligands) as
      well as with small ions and molecules in the period 2007-2014. Different modes of
      capillary electrophoretic methods, such as mobility shift (vacancy) affinity
      capillary electrophoresis, multiple injection affinity capillary electrophoresis,
      partial filling affinity capillary electrophoresis, Hummel-Dryer method, vacancy
      peak method and (continuous) frontal analysis capillary electrophoresis, are
      briefly described and their applicability to determination of binding constants
      of peptide complexes is discussed. In addition, the detailed experimental
      conditions of individual applications and the values of binding constants of the
      particular peptide complexes are presented. 

PMID- 25982956
TI  - Gold-Catalyzed Cycloisomerization and Diels-Alder Reaction of 1,4,9-Dienyne
      Esters to 3 a,6-Methanoisoindole Esters with Pro-Inflammatory Cytokine Antagonist
      Activity.
AB  - A synthetic method to prepare 3a,6-methanoisoindole esters efficiently by gold(I)
      catalyzed tandem 1,2-acyloxy migration/Nazarov cyclization followed by Diels
      Alder reaction of 1,4,9-dienyne esters is described. We also report the ability
      of one example to inhibit binding of tumor necrosis factor-alpha (TNF-alpha) to
      the tumor necrosis factor receptor 1 (TNFR1) site and TNF-alpha-induced nuclear
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) activation in
      cell at a half-maximal inhibitory concentration (IC50 ) value of 6.6 MUM. Along
      with this is a study showing the isoindolyl derivative to exhibit low toxicity
      toward human hepatocellular liver carcinoma (HepG2) cells and its possible mode
      of activity based on molecular modeling analysis. 

PMID- 25982957
TI  - Cumulative role of rare and common putative functional genetic variants at NPAS3
      in schizophrenia susceptibility.
AB  - Schizophrenia may be considered a human-specific disorder arisen as a maladaptive
      by-product of human-specific brain evolution. Therefore, genetic variants
      involved in susceptibility to schizophrenia may be identified among those genes
      related to acquisition of human-specific traits. NPAS3, a transcription factor
      involved in central nervous system development and neurogenesis, seems to be
      implicated in the evolution of human brain, as it is the human gene with most
      human-specific accelerated elements (HAEs), i.e., .mammalian conserved regulatory
      sequences with accelerated evolution in the lineage leading to humans after human
      chimpanzee split. We hypothesize that any nucleotide variant at the NPAS3 HAEs
      may lead to altered susceptibility to schizophrenia. Twenty-one variants at these
      HAEs detected by the 1000 genomes Project, as well as five additional variants
      taken from psychiatric genome-wide association studies, were genotyped in 538
      schizophrenic patients and 539 controls from Galicia. Analyses at the haplotype
      level or based on the cumulative role of the variants assuming different
      susceptibility models did not find any significant association in spite of enough
      power under several plausible scenarios regarding direction of effect and the
      specific role of rare and common variants. These results suggest that, contrary
      to our hypothesis, the special evolution of the NPAS3 HAEs in Homo relaxed the
      strong constraint on sequence that characterized these regions during mammalian
      evolution, allowing some sequence changes without any effect on schizophrenia
      risk.

PMID- 25982958
TI  - An autopsy case of fatal repellent air freshener poisoning.
AB  - We describe a first fatal case of repellent air freshener ingestion. A 79-year
      old Japanese man with Alzheimer-type senile dementia orally ingested repellent
      air freshener containing three surfactants: polyoxyethylene 9-lauryl ether,
      polyoxyethylene (40) hydrogenated castor oil, and lauric acid amidopropyl amine
      oxide (weight ratio of 1.3%). About 1h after the collapse, he was in
      cardiopulmonary arrest and subsequently died 10h after his arrival. The forensic
      autopsy performed 5.5h after death revealed the 380ml of stomach contents with a
      strong mint perfume identical to that of the repellent air freshener and the
      findings of acute death. Toxicologically, 9.1MUg/ml and 558.2MUg/ml of
      polyoxyethylene 9-lauryl ether were detected from the serum and stomach contents
      taken at autopsy. Generally, ingestion of anionic or non-ionic surfactants have
      been considered as safe. However, because the patient suffered from cardiac
      insufficiency with a low dose of repellent air freshener ingestion, medical staff
      members must evaluate the elderly patient for cardiac and circulatory problems
      regardless of the ingested dose. Not only medical and nursing staff members, but
      also families who are obliged to care for elderly persons must be vigilant to
      prevent accidental ingestion of toxic substances generally used in the household.

PMID- 25982959
TI  - MMP and TIMP temporal gene expression during osteocytogenesis.
AB  - Osteocytes within bone differentiate from osteoblast precursors which reside in a
      mineralised extracellular matrix (ECM). Fully differentiated osteocytes are
      critical for bone development and function but the factors that regulate this
      differentiation process are unknown. The enzymes primarily responsible for ECM
      remodelling are matrix metalloproteinases (MMP); however, the expression and role
      of MMPs during osteocytogenesis is undefined. Here we used MLO-A5 cells to
      determine the temporal gene expressions of the MMP family and their endogenous
      inhibitors--tissue inhibitors of metalloproteinases (TIMPs) during
      osteocytogenesis. RT-qPCR revealed expression of 14 Mmps and 3 Timps in MLO-A5
      cells. Mmp2, Mmp23 and Mmp28 were decreased concurrent with mineralisation onset
      (P < 0.05*). Mmp14 and Mmp19 mRNAs were also significantly increased at day 3 (P
      < 0.05*) before returning to baseline levels at day 6. Decreased expressions of
      Timp1, Timp2 and Timp3 mRNA were observed by day 6 compared to day 0 (P < 0.05*).
      To examine whether these changes are linked to osteocytogenesis, we determined
      Mmp/Timp mRNA expressions in mineralisation-limited conditions. RT-qPCR revealed
      that the previously observed decreases in Mmp2, Mmp23 and Mmp28 were not observed
      in these mineralisation-limited cultures, therefore closely linking these MMPs
      with osteocyte differentiation. Similarly, we found differential expression of
      Timp1, Timp2 and Timp3 mRNA in mineralisation-restricted cultures (P < 0.05*). In
      conclusion, we have identified several members of the MMP/TIMP families as
      regulators of ECM remodelling necessary for the acquisition of the osteocyte
      phenotype.

PMID- 25982961
TI  - British Icons and Catholic perfidy--Anglo-Saxon historiography and the battle for
      Crimean War nursing.
AB  - Taking as its starting point Carr's view that historical narrative reflects the
      preoccupations of the time in which it is written and Foucault's concept of
      consensual historical discourse as the outcome of a social struggle in which the
      victor suppresses or at least diminishes contrary versions of historical events
      in favour of their own, this paper traces and discusses the historical narrative
      of British nursing in the Crimean war and, in particular, three competing
      narratives that have arisen in the latter half of the 20th century and the first
      decade of the 21st. These are the established narrative surrounding Florence
      Nightingale, the new narrative surrounding Mary Seacole and an Irish narrative
      surrounding the role of the Sisters of Mercy. It is argued that the increased
      vehemence of the debate surrounding these narratives is representative of the
      changes that have taken place in British society. However, we also argue that the
      Irish narrative and its critique are reflective of deep-rooted Anglo-Protestant
      attitudes articulated by Nightingale and uncritically accepted by subsequent
      historians even in modern British historiography. 

PMID- 25982960
TI  - Leisure-time physical activity and mortality in a multiethnic prospective cohort
      study: the Northern Manhattan Study.
AB  - PURPOSE: To examine whether the survival benefit of exercise is modified by
      obesity. METHODS: In the Northern Manhattan Study, we collected baseline
      sociodemographics and cardiovascular disease risk factors. The primary exposure
      was leisure-time physical activity (LTPA) and the outcomes were total, vascular,
      and nonvascular deaths (non-VaD). LTPA was defined as any versus none and
      metabolic equivalent score category (total activity weighted by intensity). We
      used Cox models to estimate the hazard ratios (HRs) and 95% confidence intervals
      (CIs). RESULTS: A total of 3298 participants (mean age 69 years, 52% Hispanic,
      63% women) were followed over a mean of 11.8 years with 1589 total deaths (641
      vascular, 819 nonvascular). Any activity (adjusted HR: 0.84, 95% CI: 0.75-0.94)
      was associated with reduced risk of all-cause mortality and non-VaD, but not VaD.
      We found an interaction (P < .05) of LTPA with body mass index (BMI) less than 30
      for all-cause and vascular mortality. Any LTPA was associated with reduced all
      cause mortality (adjusted HR: 0.77, 95% CI: 0.68-0.87) and VaD (adjusted HR:
      0.79, 95% CI: 0.65-0.97) only among those with BMI less than 30. CONCLUSIONS: We
      found no evidence of an independent survival benefit of LTPA among those with BMI
      more than 30. The health benefits of exercise should be considered in the context
      of obesity.

PMID- 25982962
TI  - Time-dependent mechanical-electrical coupled behavior in single crystal ZnO
      nanorods.
AB  - Nanoscale time-dependent mechanical-electrical coupled behavior of single crystal
      ZnO nanorods was systematically explored, which is essential for accessing the
      long-term reliability of the ZnO nanorod-based flexible devices. A series of
      compression creep tests combined with in-situ electrical measurement was
      performed on vertically-grown single crystal ZnO nanorods. Continuous measurement
      of the current (I)-voltage (V) curves before, during, after the creep tests
      revealed that I is non-negligibly increased as a result of the time-dependent
      deformation. Analysis of the I-V curves based on the thermionic emission
      diffusion theory allowed extraction of nanorod resistance, which was shown to
      decrease as time-dependent deformation. Finally, based on the observations in
      this study, a simple analytical model for predicting the reduction in nanorod
      resistance as a function of creep strain that is induced from diffusional
      mechanisms is proposed, and this model was demonstrated to be in an excellent
      agreement with the experimental results. 

PMID- 25982963
TI  - Insulin attenuates arsenic-induced neurite outgrowth impairments by activating
      the PI3K/Akt/SIRT1 signaling pathway.
AB  - Arsenic neurotoxicity has a broad range of adverse effects on human health, which
      are induced in part by inhibition of neurite outgrowth. Insulin has been reported
      to promote neurite extension. The present study investigated whether insulin can
      protect neurons from impaired neurite outgrowth induced by arsenic, and examined
      the signaling pathway involved in this action. The study demonstrated that NaAsO2
      caused inhibition of neurite outgrowth in differentiated SH-SY5Y cells indicating
      its neurotoxicity. This inhibitory effect of NaAsO2 was attenuated by insulin. It
      was found that blocking PI3K or Akt by selective inhibitors canceled the
      protective effect of insulin against NaAsO2-induced neurite outgrowth impairment
      suggesting the essential role of active PI3K and Akt in insulin's protective
      action. Inhibition of GSK3, which mimics an effect of insulin stimulation, had no
      effect on the impairment of neurite outgrowth by NaAsO2 implying that the insulin
      protective action is probably not due to its mediation of GSK3 inhibition
      ability. Moreover, NaAsO2 decreased the Akt activity, as it caused reduction in
      Akt phosphorylation, and downregulated expression of SIRT1. Additionally, the
      reduction of these signals by NaAsO2 was attenuated by insulin. Taken together,
      these results show that insulin attenuates arsenic-induced neurite outgrowth
      impairment possibly via activation of PI3K/Akt/SIRT1 signaling, and arsenic may
      exert neurite outgrowth inhibition through a mechanism involving reduction of
      signaling molecules downstream from insulin, PI3K/Akt/SIRT1. Our findings raise
      the possibility of using insulin to combat arsenic neurotoxicity. 

PMID- 25982964
TI  - Relationships, autonomy and legal capacity: Mental capacity and support
      paradigms.
AB  - Within law and legal scholarship there are different models of legal personality
      and legal capacity. The most well known of these emphasises individual
      rationality, and is distilled into the medico-legal concept of 'mental capacity'.
      In connection with the UN Convention on the Rights of Persons with Disabilities
      (CRPD) a new approach to legal personality is being developed, emphasising
      relationships of support and recognition of universal legal capacity. Recent
      scholarship on both 'mental capacity' and CRPD approaches to legal capacity has
      drawn from feminist writings on relational autonomy. In this paper, I use this
      scholarship on relational autonomy to explore the differences between these
      approaches to legal capacity. I argue that the approach connected with the CRPD
      offers a refreshing take on the importance of relationships of support in
      exercising legal capacity. However, despite their pronounced differences,
      especially in relation to the legitimacy of coercion, there are remarkable
      similarities in the underlying challenges for each approach: the extent to which
      others can 'know' our authentic and autonomous selves, and the inextricable
      relationships of power that all forms of legal capacity are embedded within. 

PMID- 25982965
TI  - A realistic approach to assessing mental health laws' compliance with the UNCRPD.
AB  - This article argues that a more realistic view should be taken of the
      implications of the Convention on the Rights of Persons with Disabilities for
      mental health law than the view taken by the UN monitoring committee, in its
      General Comment on Equal Recognition Before the Law, in 2014. This more realistic
      interpretation would not forbid reliance on the concept of mental capacity in the
      law. Nor would it forbid legislation that authorises substitute decision-making
      or involuntary treatment. Less radical reforms, it is suggested, could promote
      Convention compliance. These reforms would shift mental health law away from
      reliance on over-broad concepts like "mental disorder" or "mental disability",
      but would still permit use of legal standards that rely on specific impairments
      in mental function that are relevant to a person's capacity to make particular
      decisions or perform specific tasks. Strong efforts would be required to promote
      supported decision-making, and respect advance directives, but substitute
      decision-making and treatment without consent would be permitted in exceptional
      circumstances, subject to appropriate safeguards and independent review. Under
      this interpretation, those measures would not constitute discrimination in the
      law on the ground of disability, or denial of equal recognition before the law.
      This approach, it is argued, is more likely to generate positive responses from
      state parties in terms of law reform. 

PMID- 25982966
TI  - Optimal programs of pathway control: dissecting the influence of pathway topology
      and feedback inhibition on pathway regulation.
AB  - BACKGROUND: Adjusting the capacity of metabolic pathways in response to rapidly
      changing environmental conditions is an important component of microbial
      adaptation strategies to stochastic environments. In this work, we use advanced
      dynamic optimization techniques combined with theoretical models to study which
      reactions in pathways are optimally targeted by regulatory interactions in order
      to minimize the regulatory effort that is required to adjust the flux through a
      complex metabolic network. Moreover, we analyze how constraints in the speed at
      which an organism can respond on a proteomic level influences these optimal
      targets of pathway control. RESULTS: We find that limitations in protein
      biosynthetic rates have a strong influence. With increasing protein biosynthetic
      rates the regulatory effort targeting the initial enzyme in a pathway is reduced
      while the regulatory effort in the terminal enzyme is increased. Studying the
      impact of allosteric regulation for different pathway topologies, we find that
      the presence of feedback inhibition by products of metabolic pathways allows
      organisms to reduce the regulatory effort that is required to control a metabolic
      pathway in all cases. In a linear pathway this even leads to the case where the
      sole transcriptional regulatory control of the terminal enzyme is sufficient to
      control flux through the entire pathway. We confirm the utilization of these
      pathway regulation strategies through the large-scale analysis of transcriptional
      regulation in several hundred prokaryotes. CONCLUSIONS: This work expands our
      knowledge about optimal programs of pathway control. Optimal targets of pathway
      control strongly depend on the speed at which proteins can be synthesized.
      Moreover, post-translational regulation such as allosteric regulation allows to
      strongly reduce the number of transcriptional regulatory interactions required to
      control a metabolic pathway across different pathway topologies.

PMID- 25982968
TI  - Application of the holmium laser lithotripsy for bladder stones under local
      anaesthesia: a prospective analysis.
AB  - PURPOSE: The purpose of this study is to determine the feasibility and the
      results of intracorporal holmium laser (HL) lithotripsy in patients with bladder
      calculus under local anaesthesia. MATERIALS AND METHODS: From January 2009 to
      August 2012, 46 patients underwent HL lithotripsy for bladder calculus under
      local anaesthesia. Twelve patients who had associated medical comorbidity also
      underwent the procedure. The pain was evaluated with 10-point visual analogue
      scale during and 1 h after completion of the procedure. Foley catheter was
      inserted at the end of procedure in all the patients. RESULTS: In the present
      study, the mean stone size was 2.1 cm (1.1-4.2 cm) and the mean operative time
      was 43 min (range 23-57 min). All patients were rendered stone-free in a single
      sitting except one patient. The mean pain score intraoperatively and in the
      postoperative period was 3.84 and 1.47, respectively. There was no major
      complication during surgery. The procedure was well tolerated and most of the
      patients were discharged on the same day. After the follow-up period of 3 months,
      all patients were asymptomatic except one patient who developed a soft stricture
      in the bulbar urethra and was managed by internal urethrotomy. CONCLUSIONS:
      Bladder stones can be safely managed by HL lithotripsy under local anaesthesia
      with a high success rate and minimal morbidity. The procedure is even feasible in
      high-risk patients with medical comorbidities without extra risk.

PMID- 25982967
TI  - Q&A: insulin secretion and type 2 diabetes: why do beta-cells fail?

PMID- 25982969
TI  - Vector Analysis of Corneal Astigmatism After Combined Femtosecond-Assisted
      Phacoemulsification and Arcuate Keratotomy.
AB  - PURPOSE: To evaluate the outcomes of femtosecond-assisted arcuate keratotomy
      combined with cataract surgery in eyes with low to moderate corneal astigmatism.
      DESIGN: Retrospective, interventional case series. METHODS: This study included
      patients who underwent combined femtosecond-assisted phacoemulsification and
      arcuate keratotomy between March 2013 and August 2013. Keratometric astigmatism
      was evaluated before and 2 months after the surgery. Vector analysis of the
      astigmatic changes was performed using the Alpins method. RESULTS: Overall, 54
      eyes of 54 patients (18 male and 36 female; mean age, 68.8 +/- 11.4 years) were
      included. The mean preoperative (target-induced astigmatism) and postoperative
      astigmatism was 1.33 +/- 0.57 diopters (D) and 0.87 +/- 0.56 D, respectively (P <
      .001). The magnitude of error (difference between surgically induced and target
      induced astigmatism) (-0.13 +/- 0.68 D), as well as the correction index (ratio
      of surgically induced and target-induced astigmatism) (0.86 +/- 0.52),
      demonstrated slight undercorrection. The angle of error was very close to 0,
      indicating no significant systematic error of misaligned treatment. However, the
      absolute angle of error showed a less favorable range (17.5 +/- 19.2 degrees),
      suggesting variable factors such as healing or alignment at an individual level.
      There were no intraoperative or postoperative complications. CONCLUSIONS:
      Combined phacoemulsification with arcuate keratotomy using femtosecond laser
      appears to be a relatively easy and safe means for management of low to moderate
      corneal astigmatism in cataract surgery candidates. Misalignment at an individual
      level can reduce its effectiveness. This issue remains to be elucidated in future
      studies.

PMID- 25982970
TI  - Lamellar Hole-Associated Epiretinal Proliferation in Comparison to Epiretinal
      Membranes of Macular Pseudoholes.
AB  - PURPOSE: To compare immunocytochemical and ultrastructural characteristics of
      "lamellar hole-associated epiretinal proliferation" in lamellar macular holes
      with "conventional epiretinal membrane" in macular pseudoholes. DESIGN: A
      consecutive observational case series, laboratory investigation. METHODS: We
      analyzed surgically excised flat-mounted internal limiting membrane specimens and
      epiretinal membrane specimens removed from 25 eyes of 25 patients with lamellar
      macular holes (11 eyes) and macular pseudoholes (14 eyes) using interference and
      phase-contrast microscopy, immunocytochemistry, and transmission electron
      microscopy. By spectral-domain optical coherence tomography, epiretinal material
      of homogenous reflectivity without contractive properties was categorized as
      lamellar hole-associated epiretinal proliferation, whereas tractional epiretinal
      membranes presenting contractive properties were termed conventional epiretinal
      membrane. RESULTS: Lamellar hole-associated epiretinal proliferation was seen in
      73% of eyes with lamellar macular hole. Eyes with macular pseudohole presented
      with conventional epiretinal membrane. In lamellar hole-associated epiretinal
      proliferation, positive immunoreactivity for anti-glial fibrillary acidic
      protein, hyalocyte markers, and anti-collagen type I and III was seen. In
      contrast, specimens of macular pseudoholes were positive for alpha-smooth muscle
      actin and anti-glial fibrillary acidic protein, predominantly. Cellular
      ultrastructure showed that lamellar hole-associated epiretinal proliferation of
      lamellar macular holes mainly consisted of fibroblasts and hyalocytes, whereas
      myofibroblasts dominated in conventional epiretinal membranes of macular
      pseudoholes. CONCLUSIONS: Cells within lamellar hole-associated epiretinal
      proliferation appear to originate from vitreous and possess less contractive
      properties than cells of conventional epiretinal membranes. Our findings point to
      differences in pathogenesis in a subgroup of lamellar macular holes presenting
      lamellar hole-associated epiretinal proliferation on the retinal surface.

PMID- 25982971
TI  - Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in
      Patients With Molecularly Confirmed Bardet-Biedl Syndrome.
AB  - PURPOSE: To describe a series of patients with Bardet-Biedl syndrome (BBS) and
      predominantly retinal cone dysfunction, a previously only rarely reported
      association. DESIGN: Retrospective observational case series. METHODS: Seven
      patients with clinically proven Bardet-Biedl syndrome had undergone detailed
      ocular phenotyping, which included fundus examination, Goldmann visual fields,
      fundus autofluorescence imaging (FAF), optical coherence tomography (OCT), and
      electroretinography (ERG). Mutational screening in the BBS genes was performed
      either by direct Sanger sequencing or targeted next-generation sequencing.
      RESULTS: All 7 patients had proven BBS mutations; 1 had a cone dystrophy
      phenotype on ERG and 6 had a cone-rod pattern of dysfunction. Macular atrophy was
      present in all patients, usually with central hypofluorescence surrounded by a
      continuous hyperfluorescent ring on fundus autofluorescence imaging. OCT
      confirmed loss of outer retinal structure within the atrophic areas. No clear
      genotype-phenotype relationship was evident. CONCLUSIONS: Patients with Bardet
      Biedl syndrome usually develop early-onset retinitis pigmentosa. In contrast, the
      patients described herein, with molecularly confirmed Bardet-Biedl syndrome,
      developed early cone dysfunction, including the first reported case of a cone
      dystrophy phenotype associated with the disorder. The findings significantly
      expand the phenotype associated with Bardet-Biedl syndrome.

PMID- 25982972
TI  - Increased Fundus Autofluorescence and Progression of Geographic Atrophy Secondary
      to Age-Related Macular Degeneration: The GAIN Study.
AB  - PURPOSE: To define the role of increased fundus autofluorescence (FAF), a
      surrogate for lipofuscin content, as a risk factor for progression of geographic
      atrophy (GA). DESIGN: Prospective natural history cohort study, the GAIN
      (Characterization of geographic atrophy progression in patients with age-related
      macular degeneration). METHODS: setting: Single-center study conducted in
      Barcelona, Spain. PATIENTS: After screening of 211 patients, 109 eyes of 82
      patients with GA secondary to age-related macular degeneration and a minimum
      follow-up of 6 months were included. OBSERVATION PROCEDURES: Lipofuscin content
      was classified independently by 2 masked observers according to FAF patterns
      described previously. Bivariate, stratified, and multivariable analyses were used
      to explore the associations between GA growth and independent variables.
      Mediation analysis was used to evaluate the contribution of FAF patterns to GA
      progression. MAIN OUTCOME: Progression of GA in mm(2)/year as measured with FAF.
      RESULTS: Median follow-up was 18 months (range, 6-42). Median GA growth was 1.61
      mm(2)/year. FAF, baseline area of atrophy, and time of follow-up were
      independently associated with GA progression (P < .004). FAF patterns and
      baseline area of atrophy were strongly associated (P < .0001), suggesting
      potential confounding. Mediation analysis suggested that most of the effect of
      FAF patterns on GA growth was actually caused by baseline area of atrophy.
      CONCLUSIONS: FAF patterns, baseline area of atrophy, and time of follow-up were
      associated with GA progression. However, FAF patterns seem to be a consequence
      (not a cause) of enlarging atrophy and their effect on GA progression seems
      mostly driven by baseline area of atrophy.

PMID- 25982973
TI  - Identification of Drusen Characteristics in Age-Related Macular Degeneration by
      Polarization-Sensitive Optical Coherence Tomography.
AB  - PURPOSE: To describe qualitative characteristics of drusen in eyes with
      nonadvanced age-related macular degeneration (AMD) using polarization-sensitive
      optical coherence tomography (OCT). DESIGN: Cross-sectional study. METHODS:
      Twenty-five eyes of 25 patients with early to intermediate (nonadvanced) AMD were
      imaged with polarization-sensitive OCT using macular volume scans. All individual
      drusen in each B-scan were manually delineated by experts certified by a reading
      center and graded for 6 different morphologic characteristics based on a defined
      classification scheme, including the presence of internal depolarizing structures
      and associated depolarizing foci. With the use of a custom-made software, the
      central B-scan of each individual druse was selected and used to analyze its
      location, diameter, and characteristics and assess the prevalence of the
      different features and relations between them. RESULTS: Using the macular volume
      scans, 6224 individual drusen could be identified, including their position
      within the retina, their characteristics, and their association with any
      pigmentary alterations. The most common drusen type was a convex-shaped druse
      with homogeneous medium internal reflectivity and no depolarizing contents (55.3%
      of drusen). A total of 30.5% of the drusen exhibited internal depolarizing
      material; 0.3% presented overlying hyperreflective foci, and in 54.5% the foci
      were also depolarizing. Significant correlations were found between the diameter
      of the drusen and their distribution throughout the retina, shape, homogeneity of
      internal reflectivity, presence of internal depolarizing characteristics, and
      presence of overlying foci (P < .001 each). Significant relations were found
      between reflectivity, homogeneity, and polarization-sensitive internal
      characteristics (P < .001). CONCLUSIONS: Polarization-sensitive OCT reveals
      characteristic morphologic features of different druse types highlighting the
      pathophysiological spectrum of early to intermediate AMD.

PMID- 25982975
TI  - Pseudogene-Expressed RNAs: Emerging Roles in Gene Regulation and Disease.
AB  - Pseudogenes have for long been considered as non-functional relics littering the
      human genome. Only now, it is becoming apparent that many pseudogenes are
      transcribed into long noncoding RNAs, some with proven biological functions.
      Here, we review the current knowledge of pseudogenes and their widespread
      functional properties with an emphasis on pseudogenes that have been functionally
      investigated in greater detail. Pseudogenes are emerging as a novel class of long
      noncoding RNAs functioning, for example, through microRNA sponging and chromatin
      remodeling. The examples discussed herein underline that pseudogene-encoded RNAs
      are important regulatory molecules involved in diseases such as cancer. 

PMID- 25982974
TI  - Developing a climate-based risk map of fascioliasis outbreaks in Iran.
AB  - The strong relationship between climate and fascioliasis outbreaks enables the
      development of climate-based models to estimate the potential risk of
      fascioliasis outbreaks. This work aims to develop a climate-based risk map of
      fascioliasis outbreaks in Iran using Ollerenshaw's fascioliasis risk index
      incorporating geographical information system (GIS). Using this index, a risk map
      of fascioliasis outbreaks for the entire country was developed. We determined
      that the country can be divided into 4 fascioliasis outbreak risk categories.
      Class 1, in which the Mt value is less than 100, includes more than 0.91 of the
      country's area. The climate in this class is not conducive to fascioliasis
      outbreaks in any month. Dryness and low temperature in the wet season (December
      to April) are the key barriers against fascioliasis outbreaks in this class. The
      risk map developed based on climatic factors indicated that only 0.03 of the
      country's area, including Gilan province in the northern region of Iran, is
      highly suitable to fascioliasis outbreaks during September to January. The Mt
      value is greater than 500 in this class. Heavy rainfall in the summer and fall,
      especially in Rasht, Astara and Bandar Anzaly (>= 1000 mm/year), creates more
      suitable breeding places for snail intermediate hosts.

PMID- 25982976
TI  - Understanding the Complex Circuitry of lncRNAs at the X-inactivation Center and
      Its Implications in Disease Conditions.
AB  - Balanced gene expression is a high priority in order to maintain optimal
      functioning since alterations and variations could result in acute consequences.
      X chromosome inactivation (X-inactivation) is one such strategy utilized by
      mammalian species to silence the extra X chromosome in females to uphold a
      similar level of expression between the two sexes. A functionally versatile class
      of molecules called long noncoding RNA (lncRNA) has emerged as key regulators of
      gene expression and plays important roles during development. An lncRNA that is
      indispensable for X-inactivation is X-inactive specific transcript (Xist), which
      induces a repressive epigenetic landscape and creates the inactive X chromosome
      (Xi). With recent advents in the field of X-inactivation, novel positive and
      negative lncRNA regulators of Xist such as Jpx and Tsix, respectively, have
      broadened the regulatory network of X-inactivation. Xist expression failure or
      dysregulation has been implicated in producing developmental anomalies and
      disease states. Subsequently, reactivation of the Xi at a later stage of
      development has also been associated with certain tumors. With the recent influx
      of information about lncRNA biology and advancements in methods to probe lncRNA,
      we can now attempt to understand this complex network of Xist regulation in
      development and disease. It has become clear that the presence of an extra set of
      genes could be fatal for the organism. Only by understanding the precise ways in
      which lncRNAs function can treatments be developed to bring aberrations under
      control. This chapter summarizes our current understanding and knowledge with
      regard to how lncRNAs are orchestrated at the X-inactivation center (Xic), with a
      special focus on how genetic diseases come about as a consequence of lncRNA
      dysregulation. 

PMID- 25982977
TI  - Open source tools for large-scale neuroscience.
AB  - New technologies for monitoring and manipulating the nervous system promise
      exciting biology but pose challenges for analysis and computation. Solutions can
      be found in the form of modern approaches to distributed computing, machine
      learning, and interactive visualization. But embracing these new technologies
      will require a cultural shift: away from independent efforts and proprietary
      methods and toward an open source and collaborative neuroscience. 

PMID- 25982978
TI  - Theory of mind and social functioning in patients with temporal lobe epilepsy.
AB  - OBJECTIVE: This study aimed to explore the effects of theory of mind (ToM) and
      related potential risk factors, including cognitive functions, psychiatric
      status, and seizure-related clinical variables, on social functioning in patients
      with temporal lobe epilepsy (TLE). METHODS: Sixty-seven patients with intractable
      TLE who were potential candidates for epilepsy surgery and 30 matched controls
      were included. All participants completed four tasks measuring different levels
      of ToM (False Belief, Faux Pas Recognition, Implication Stories, and Visual
      Cartoon), the Symptom Checklist-90-Revised (SCL-90-R), the Social and
      Occupational Functioning Scale for Epilepsy (SOFSE), and neuropsychological
      tests. RESULTS: The patients exhibited impairments in both basic and advanced
      ToM. Multiple regression analyses revealed the following: (1) the SOFSE total
      score was significantly predicted by the Faux Pas Recognition (FPR), Global
      Severity Index (GSI) score of the SCL-90-R, and Full-Scale intelligence quotient
      (IQ) of the Wechsler Adult Intelligence Scale (WAIS), which accounted for 38%,
      11%, and 8% of the variance, respectively; and (2) the FPR was a significant
      predictor of all SOFSE subscales, whereas the GSI score contributed substantially
      to the Interpersonal Relationships, Communication, and Occupation subscales of
      the SOFSE. SIGNIFICANCE: Advanced ToM, measured by impaired faux pas recognition,
      is a relatively strong predictor of poor social functioning in surgical
      candidates for intractable TLE. Identifying ToM impairment may help plan
      nonpharmacologic treatment for improving social functions in patients with
      intractable TLE.

PMID- 25982979
TI  - New isotopic evidence of lead contamination in wheat grain from atmospheric
      fallout.
AB  - Crops could accumulate trace metals by soil-root transfer and foliar uptake from
      atmospheric fallout, and an accurate assessment of pollution sources is a
      prerequisite for preventing heavy metal pollution in agricultural products. In
      this study, we examined Pb isotope rates to trace the sources of Pb in wheat
      grain grown in suburbs. Results showed that, even in zones with scarcely any air
      pollution spots, atmospheric fallout was still a considerable source of Pb
      accumulation in wheat. The concentration of Pb in wheat grain has poor
      correlation with that in farm soil. The Pb concentration in wheat grains with
      dust in bran coat was significantly higher than that in wheat grains, which
      indicates that Pb may accumulate by foliar uptake. The Pb isotope rate has
      obvious differences between the soil and atmospheric fallout, and scatter ratio
      is significantly closer between the wheat grain and atmospheric fallout.
      Atmospheric fallout is a more significant source of Pb concentration in wheat
      grains than in soil. As far as we know, this is the first study on the main
      sources of lead in grain crop (wheat) samples with isotope. This study aims to
      improve our understanding of the translocation of foliar-absorbed metals to
      nonexposed parts of plants. 

PMID- 25982980
TI  - Assessment of water quality in urban streams based on larvae of Hydropsyche
      angustipennis (Insecta, Trichoptera).
AB  - Hydropsyche angustipennis (Insecta, Trichoptera) larvae were used as indicators
      of stream contamination in the city of Lodz, Poland. The larvae of H.
      angustipennis were present at 9 sampling sites established for this study.
      Significant differences between the sampling sites were noted for environmental
      parameters as well as concentration of chemicals in water and biodiversity of
      aquatic invertebrates. Statistical analyses showed significant correlations
      between quantity and quality of water pollutants and density of H. angustipennis
      larvae, concentration of metals in larval bodies, and the appearance of
      morphological anomalies in tracheal gills and anal papillae. In comparison to
      literature data, the level of contaminants in water, including heavy metals, for
      each of the studied streams of Lodz was surprisingly low while concentration of
      these metals in the whole bodies of H. angustipennis larvae was very high. Some
      of the heavy metals present in the water might be identified only after
      conducting analyses of their concentration in the larval bodies. Therefore, long
      life cycle of H. angustipennis and heavy metal tolerance with a possibility of
      their accumulation in the larval bodies may constitute a support to traditional
      chemical assessment of water quality or traditional biomonitoring.

PMID- 25982981
TI  - Using pre-screening methods for an effective and reliable site characterization
      at megasites.
AB  - This paper illustrates the usefulness of pre-screening methods for an effective
      characterization of polluted sites. We applied a sequence of site
      characterization methods to a former Soviet military airbase with likely fuel and
      benzene, toluene, ethylbenzene, and xylene (BTEX) contamination in shallow
      groundwater and subsoil. The methods were (i) phytoscreening with tree cores;
      (ii) soil gas measurements for CH4, O2, and photoionization detector (PID); (iii)
      direct-push with membrane interface probe (MIP) and laser-induced fluorescence
      (LIF) sensors; (iv) direct-push sampling; and (v) sampling from soil and from
      groundwater monitoring wells. Phytoscreening and soil gas measurements are rapid
      and inexpensive pre-screening methods. Both indicated subsurface pollution and
      hot spots successfully. The direct-push sensors yielded 3D information about the
      extension and the volume of the subsurface plume. This study also expanded the
      applicability of tree coring to BTEX compounds and tested the use of high
      resolution direct-push sensors for light hydrocarbons. Comparison of screening
      results to results from conventional soil and groundwater sampling yielded in
      most cases high rank correlation and confirmed the findings. The large-scale
      application of non- or low-invasive pre-screening can be of help in directing and
      focusing the subsequent, more expensive investigation methods. The rapid pre
      screening methods also yielded useful information about potential remediation
      methods. Overall, we see several benefits of a stepwise screening and site
      characterization scheme, which we propose in conclusion.

PMID- 25982982
TI  - Changes in water quality of treated sewage effluents by their receiving
      environments in Tablas de Daimiel National Park, Spain.
AB  - The Tablas de Daimiel National Park (TDNP), a floodplain wetland located in the
      Upper Guadiana Basin (central Spain), receives pollution from wastewater
      treatment plants (WWTPs) discharging their treated sewage effluents (TSEs) to
      tributary channels to the wetland. The TSEs suffer transformations on their way
      to the TDNP, but the water quality is controlled only at the point of discharge.
      In this work, we analyse the change in water quality of the TSE from four urban
      WWTPs in the surroundings of the TDNP (Alcazar de San Juan, Daimiel, Manzanares
      and Villarrubia de los Ojos towns). The water samples were taken at the outlet of
      the plants and in the receiving environments, to analyse the water quality
      transformation of the TSE. The different discharge configurations of each WWTP
      have been related with the water quality transformation of their TSE, to
      interpret the influence of the hydro-geomorphology in the improvement or
      deterioration of the water quality of TSE. We found that the discharge of TSE
      into slow flow channels with macrophyte vegetation facilitates water self
      purification but, with time, the accumulation of sludge in the beds of the
      effluents tends to be the cause of the deterioration of the water quality. 

PMID- 25982983
TI  - Investigation of the available technologies and their feasibility for the
      conversion of food waste into fish feed in Hong Kong.
AB  - Food waste is the largest constituent of municipal solid waste in Hong Kong, but
      food waste recycling is still in its infancy. With the imminent saturation of all
      landfill sites by 2020, multiple technologies are needed to boost up the food
      waste recycling rate in Hong Kong. Conversion of food waste into animal feeds is
      prevalent in Japan, South Korea, and Taiwan, treating over 40 % of their recycled
      food waste. This direction is worth exploring in Hong Kong once concerns over
      food safety are resolved. Fortunately, while feeding food waste to pigs and
      chickens poses threats to public health, feeding it to fish is considered low
      risk. In order to examine the feasibility of converting food waste into fish feed
      in Hong Kong, this paper investigates the market demand, technical viability,
      feed quality, regulatory hurdles, and potential contribution. The results show
      that a significant amount of food waste can be recycled by converting it into
      fish feed due to the enormous demand from feed factories in mainland China. Two
      conversion technologies, heat drying and black soldier fly bioconversion, are
      studied extensively. Black soldier fly bioconversion is preferable because the
      end-product, insect powder, is anticipated to gain import approval from mainland
      China. The authors suggest further research efforts to speed up its application
      for food waste recycling in urban cities. 

PMID- 25982984
TI  - Dynamics of microbiological parameters, enzymatic activities and worm biomass
      production during vermicomposting of effluent treatment plant sludge of bakery
      industry.
AB  - This paper reports the changes in microbial parameters and enzymatic activities
      during vermicomposting of effluent treatment plant sludge (ETPS) of bakery
      industry spiked with cow dung (CD) by Eisenia fetida. Six vermibins containing
      different ratios of ETPS and CD were maintained under controlled laboratory
      conditions for 15 weeks. Total bacterial and total fungal count increased upto
      7th week and declined afterward in all the bins. Maximum bacterial and fungal
      count was 31.6 CFU * 10(6) g(-1) and 31 CFU * 10(4) g(-1) in 7th week. Maximum
      dehydrogenase activity was 1921 MUg TPF g(-1) h(-1) in 9th week in 100 % CD
      containing vermibin, whereas maximum urease activity was 1208 MUg NH4 (-)N g(-1)
      h(-1) in 3rd week in 100 % CD containing vermibin. The enzyme activity and
      microbial counts were lesser in ETPS containing vermibins than control (100 %
      CD). The growth and fecundity of the worms in different vermibins were also
      investigated. The results showed that initially biomass and fecundity of the
      worms increased but decreased at the later stages due to non-availability of the
      palatable feed. This showed that quality and palatability of food directly affect
      biological parameters of the system.

PMID- 25982985
TI  - Improvement of anaerobic digestion of waste-activated sludge by using H2O2
      oxidation, electrolysis, electro-oxidation and thermo-alkaline pretreatments.
AB  - Disintegration of municipal waste-activated sludge (WAS) is regarded as a
      prerequisite of the anaerobic digestion process to reduce sludge volume and
      improve biogas yield. Pretreatment of WAS using thermo-alkaline (TA), H2O2
      oxidation, electrolysis and electro-oxidation (EO) processes were investigated
      and compared in term of COD solubilization and biogas production. For each
      pretreatment, the influences of different operational variables were studied in
      detail. At optimum conditions, EO gave the maximum COD solubilization (28 %). The
      effects of pretreatments under the optimum conditions on anaerobic digestion were
      experienced with biochemical methane potential assay. Significant increases in
      biogas yield up to 78 and 40 % were observed respectively in the EO and TA
      pretreated samples compared to raw sludge. Results clearly revealed that the
      application of EO is a significant alternative method for the improvement of WAS
      anaerobic digestion.

PMID- 25982986
TI  - Airborne mineral components and trace metals in Paris region: spatial and
      temporal variability.
AB  - A variety of mineral components (Al, Fe) and trace metals (V, Cr, Mn, Ni, Cu, Zn,
      Cd, Pb) were simultaneously measured in PM2.5 and PM10 fractions at three
      different locations (traffic, urban, and suburban) in the Greater Paris Area
      (GPA) on a daily basis throughout a year. Mineral species and trace metal levels
      measured in both fractions are in agreement with those reported in the literature
      and below the thresholds defined by the European guidelines for toxic metals (Cd,
      Ni, Pb). Size distribution between PM2.5 and PM10 fractions revealed that mineral
      components prevail in the coarse mode, while trace metals are mainly confined in
      the fine one. Enrichment factor analysis, statistical analysis, and seasonal
      variability suggest that elements such as Mn, Cr, Zn, Fe, and Cu are attributed
      to traffic, V and Ni to oil combustion while Cd and Pb to industrial activities
      with regional origin. Meteorological parameters such as rain, boundary layer
      height (BLH), and air mass origin were found to significantly influence element
      concentrations. Periods with high frequency of northern and eastern air masses
      (from high populated and industrialized areas) are characterized by high metal
      concentrations. Finally, inner city and traffic emissions were also evaluated in
      PM2.5 fraction. Significant contributions (>50 %) were measured in the traffic
      site for Mn, Fe, Cr, Zn, and Cu, confirming that vehicle emissions contribute
      significantly to their levels, while in the urban site, the lower contributions
      (18 to 33 %) for all measured metals highlight the influence of regional sources
      on their levels.

PMID- 25982987
TI  - Effect of passivator on Cu form transformation in pig manure aerobic composting
      and application in soil.
AB  - A sequential extraction approach was used to evaluate the effects of various
      combinations of passivators (sepiolite, phosphate rock, and coal fly ash) on the
      concentration and speciation of Cu in swine manure aerobic compost along with
      soil to which the compost had been applied. The results indicate that the various
      passivators altered the bound forms of Cu in pig manure and soil; the
      concentrations of exchangeable and Fe-Mn-bound Cu decreased, whereas the residual
      Cu concentration increased, indicating that Cu transformed to low-availability
      forms after the passivator treatments. The concentrations of the carbonate-bound
      and organic-bound Cu varied widely. Among all treatments, the treatment of the
      control + straw + sepiolite + coal fly ash (2.5 %) + phosphate rock (5.0 %)
      resulted in the most efficient passivation of Cu; the percentage of residual Cu
      reached 3.91-21.14 %, obviously surpassing the percentage for the control without
      passivation. The treatment of the control + straw + sepiolite + phosphate rock
      (2.5 %) resulted in the lowest residual Cu fraction (0.85 %) among passivator
      treatments. These results show that the addition of suitable combinations of
      passivators to the composting process reduced the availability of Cu and the risk
      of Cu pollution during the application of composted pig manure to soil.
      Passivation also decreased the Cu content of Apium graveolens.

PMID- 25982988
TI  - Anniston community health survey: Follow-up and dioxin analyses (ACHS-II)-
      methods.
AB  - High serum concentrations of polychlorinated biphenyls (PCBs) have been reported
      previously among residents of Anniston, Alabama, where a PCB production facility
      was located in the past. As the second of two cross-sectional studies of these
      Anniston residents, the Anniston Community Health Survey: Follow-Up and Dioxin
      Analyses (ACHS-II) will yield repeated measurements to be used to evaluate
      changes over time in ortho-PCB concentrations and selected health indicators in
      study participants. Dioxins, non-ortho PCBs, other chemicals, heavy metals, and a
      variety of additional clinical tests not previously measured in the original ACHS
      cohort will be examined in ACHS-II. The follow-up study also incorporates a
      questionnaire with extended sections on diet and occupational history for a more
      comprehensive assessment of possible exposure sources. Data collection for ACHS
      II from 359 eligible participants took place in 2014, 7 to 9 years after ACHS.

PMID- 25982989
TI  - Polychlorinated biphenyls and organochlorine pesticides in surface sediments from
      the sand flats of Shuangtaizi Estuary, China: levels, distribution, and possible
      sources.
AB  - Levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs)
      in sediments from the sandy flat system of Shuangtaizi Estuary, the highest
      latitude estuary in China, were investigated to identify their possible sources
      and potential ecological risk. The concentrations of 28 PCBs and 18 OCPs ranged
      from 1.83 to 36.68 ng g(-1) dw (mean 10.53 ng g(-1) dw) and from 0.02 to 14.57 ng
      g(-1) dw (mean 5.65 ng g(-1) dw), respectively. Generally, these organic
      pollutants showed an obvious spatial distribution, and relatively high levels
      were found at the high-tidal zone near river mouths. Compositional analyses
      indicated that tetra-PCBs were dominant for PCBs, whereas heptachlor was
      identified to be prevalent for OCPs in surficial sediment in the sand flats of
      Shuangtaizi Estuary. Overall, Shuangtaizi Estuary had moderate PCB and OCP levels
      in the sand flat sediments and posed a low ecological hazard to aquatic biota.
      Our results indicated that the sediment PCBs came from nonpoint deposition, such
      as atmospheric contribution and river input, for light chlorinated congeners and
      point source deposition, such as the industrial sources along river flow, for
      highly chlorinated congeners, whereas OCPs originate mainly from old residuals
      and new usage of pesticides in agriculture and aquaculture. 

PMID- 25982990
TI  - Colcemid treatment during oocyte maturation improves preimplantation development
      of cloned pig embryos by influencing meiotic progression and cytoplasmic
      maturation.
AB  - The objective of this study was to examine the effects of colcemid treatment
      during oocyte in vitro maturation (IVM) and embryonic development after
      parthenogenetic activation (PA) and somatic-cell nucleus transfer (SCNT) in pigs.
      Immature oocytes were treated with colcemid from 0 to 22, 38 to 42, or 0 to 22 hr
      followed by 38 to 42 hr during IVM (designated as COL0-22, COL38-42, and COL0
      22/38-42, respectively). The proportion of oocytes reaching the germinal vesicle
      (GV)/GV breakdown (GVBD) stage after 22 hr of IVM was higher in COL0-22 (98.4%)
      than in controls not exposed to colcemid (68.7%). The proportion of metaphase-II
      (MII) oocytes after 30 hr of IVM was higher in control (79.6%) than in COL0-22
      oocytes (61.7%); overall nuclear progression to the MII stage was not influenced
      by colcemid treatment by the end of the IVM period (93.8, 86.7, 86.8, and 84.8%
      for control, COL0-22, COL38-42, and COL0-22/38-42, respectively). COL0-22 oocytes
      showed higher intra-oocyte glutathione content (1.7 vs. 1.0-1.3 pixels/oocyte)
      and increased blastocyst formation after PA (68.7% vs. 42.5-52.2%) and SCNT
      (39.4% vs. 16.3-28.6%) than control, COL38-42, and COL0-22/38-42 oocytes.
      Colcemid treatment for 0-22 and 0-22/38-42 hr of IVM also stimulated the
      expression of cyclin-dependent kinase 1 (CDK1), proliferating cell nuclear
      antigen (PCNA), and extracellular signal-regulated kinase 2 (ERK2) mRNAs. Our
      results thus demonstrate that the presence of colcemid during the early stage of
      IVM stimulates preimplantation development of PA and SCNT porcine embryos by
      improving the cytoplasmic microenvironment.

PMID- 25982991
TI  - Gas sensing using porous materials for automotive applications.
AB  - Improvements in the efficiency of combustion within a vehicle can lead to
      reductions in the emission of harmful pollutants and increased fuel efficiency.
      Gas sensors have a role to play in this process, since they can provide real time
      feedback to vehicular fuel and emissions management systems as well as reducing
      the discrepancy between emissions observed in factory tests and 'real world'
      scenarios. In this review we survey the current state-of-the-art in using porous
      materials for sensing the gases relevant to automotive emissions. Two broad
      classes of porous material - zeolites and metal-organic frameworks (MOFs) - are
      introduced, and their potential for gas sensing is discussed. The adsorptive,
      spectroscopic and electronic techniques for sensing gases using porous materials
      are summarised. Examples of the use of zeolites and MOFs in the sensing of water
      vapour, oxygen, NOx, carbon monoxide and carbon dioxide, hydrocarbons and
      volatile organic compounds, ammonia, hydrogen sulfide, sulfur dioxide and
      hydrogen are then detailed. Both types of porous material (zeolites and MOFs)
      reveal great promise for the fabrication of sensors for exhaust gases and vapours
      due to high selectivity and sensitivity. The size and shape selectivity of the
      zeolite and MOF materials are controlled by variation of pore dimensions,
      chemical composition (hydrophilicity/hydrophobicity), crystal size and
      orientation, thus enabling detection and differentiation between different gases
      and vapours. 

PMID- 25982992
TI  - The effect of wind turbine noise on sleep and quality of life: A systematic
      review and meta-analysis of observational studies.
AB  - Noise generated by wind turbines has been reported to affect sleep and quality of
      life (QOL), but the relationship is unclear. Our objective was to explore the
      association between wind turbine noise, sleep disturbance and quality of life,
      using data from published observational studies. We searched Medline, Embase,
      Global Health and Google Scholar databases. No language restrictions were
      imposed. Hand searches of bibliography of retrieved full texts were also
      conducted. The reporting quality of included studies was assessed using the
      STROBE guidelines. Two reviewers independently determined the eligibility of
      studies, assessed the quality of included studies, and extracted the data. We
      included eight studies with a total of 2433 participants. All studies were cross
      sectional, and the overall reporting quality was moderate. Meta-analysis of six
      studies (n=2364) revealed that the odds of being annoyed is significantly
      increased by wind turbine noise (OR: 4.08; 95% CI: 2.37 to 7.04; p<0.00001). The
      odds of sleep disturbance was also significantly increased with greater exposure
      to wind turbine noise (OR: 2.94; 95% CI: 1.98 to 4.37; p<0.00001). Four studies
      reported that wind turbine noise significantly interfered with QOL. Further,
      visual perception of wind turbine generators was associated with greater
      frequency of reported negative health effects. In conclusion, there is some
      evidence that exposure to wind turbine noise is associated with increased odds of
      annoyance and sleep problems. Individual attitudes could influence the type of
      response to noise from wind turbines. Experimental and observational studies
      investigating the relationship between wind turbine noise and health are
      warranted. 

PMID- 25982993
TI  - Inspiratory muscle training in patients with diabetic autonomic neuropathy: a
      randomized clinical trial.
AB  - AIMS AND METHODS: We evaluated the effects of an 8-week inspiratory muscle
      training (IMT, n = 5) or placebo IMT (P-IMT, n = 5) on maximal respiratory
      pressures, pulmonary function, functional capacity, and cardiac autonomic control
      in patients with type 2 diabetes and diabetic autonomic neuropathy (DAN). RESULTS
      AND CONCLUSIONS: The IMT group had a greater increase in maximum inspiratory
      pressure as compared to P-IMT (p < 0.05). The IMT improved inspiratory muscle
      strength in patients with DAN.

PMID- 25982994
TI  - Platelet destruction in immune thrombocytopenia. Understanding the mechanisms.
AB  - Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by
      isolated thrombocytopenia. A dysfunctional proliferation of autoreactive T cells
      is suggested to be responsible for the loss of tolerance to self-platelet
      antigens in ITP patients. Autoreactive T cells induce uncontrolled proliferation
      of autoantibody producing B cells leading to persistent anti-platelet
      autoimmunity in some ITP patients. The autoimmune response causes an increased
      destruction of platelets by antibody-mediated phagocytosis, complement activation
      but also by T cell mediated cytotoxicity. In addition, abnormalities in
      thrombopoiesis and insufficient platelet production due to antibody or T cell
      mediated megakaryocyte inhibition and destruction contribute to the
      pathophysiology of ITP. These various effector cell responses may account for the
      heterogeneity in the clinical manifestation of ITP and also, to success or
      failure of different treatment strategies. A better understanding of the
      mechanisms behind ITP will hopefully allow for better diagnostic and,
      particularly, therapeutic strategies in the future. 

PMID- 25982995
TI  - Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by
      inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen
      induced arthritis.
AB  - Our aim is to elucidate the effects of osteoproteogerin (OPG) on cartilage
      destruction in rats as a model of collagen-induced arthritis (CIA). To establish
      the CIA model, Sprague Dawley rats were injected with bovine type II collagen
      solution subcutaneously via the tails. Adenovirus-mediated OPG (Ad-OPG) was then
      injected intra-articularly either at the beginning of CIA (early OPG treatment)
      or one week after CIA establishment (late OPG treatment); vehicle or Ad-green
      fluorescent protein were injected as controls. The rats were killed 4 weeks after
      treatment. Ankle-joint sections were obtained for histology. Serum samples were
      collected for enzyme-linked immunosorbent assay. Safranin O staining showed that
      proteoglycan loss was inhibited in the early and late Ad-OPG groups. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining revealed
      that both early and late Ad-OPG treatments significantly prevented chondrocyte
      apoptosis in CIA rats. Furthermore, disintegrin and metalloproteinase with
      thrombospondin motif-5 expression decreased remarkably in the early and late OPG
      treatment groups. However, the cartilage destruction score, cartilage oligomeric
      matrix protein level and caspase-3 expression were only decreased in the early Ad
      OPG treatment group. Additionally, ankle-joint swelling and the interleukin-1beta
      expression level in CIA rats were not notably altered by Ad-OPG treatment. Taken
      together, our results suggest that early Ad-OPG treatment has potent protective
      effects against cartilage destruction during rheumatoid arthritis progression,
      mainly by reducing proteoglycan loss and chondrocyte apoptosis. 

PMID- 25982996
TI  - Clinical management of radicular pain.
AB  - This review provides an overview of the diagnosis and treatment strategies for
      the management of radicular pain. While it is not as common as axial spinal pain,
      radicular pain combines the advantage of leveraging appropriate diagnostic
      strategies and definitive treatments with well-informed outcome measures.
      Multiple diagnostic measures include not only history and physical examination,
      but also imaging. The treatment modalities include pharmacologic management,
      physical and rehabilitation measures, interventional techniques and surgical
      treatments. Here, the authors describe the prevalence and pathophysiology of
      radicular pain, risk factors, diagnostic strategies, treatment modalities and the
      evidence for these management strategies. Finally, the authors show the efficacy
      of conservative management, despite surgical management being the gold standard. 

PMID- 25982997
TI  - Inefficient induction and spread of seeded tau pathology in P301L mouse model of
      tauopathy suggests inherent physiological barriers to transmission.

PMID- 25982998
TI  - Integrin beta6 can be translationally regulated by eukaryotic initiation factor
      4E: Contributing to colonic tumor malignancy.
AB  - It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin
      alphavbeta6 can contribute to malignant behavior of colon cancer. We have found
      that integrin alphavbeta6 and eIF4E were co-expressed and positively correlated
      in colon cancer tissues. Recently, deregulation of the protein synthesis
      apparatus has begun to gain attention as a major participant in cancer
      development and progression. However, the regulation of integrin beta6 expression
      at translational level has never been investigated before. In present study, gene
      silencing technique for eIF4E by small interfering RNA (siRNA) was used in all
      the subsequent experiments, in order to investigate whether eIF4E could
      translationally regulate expression of integrin beta6 in colon cancer SW480 and
      HT-29 cell lines. Additionally, the subsequent effects of eIF4E knockdown on
      cellular malignant behavior were observed. siRNA in SW480 and HT-29
      transfectants. Subsequently, protein expression of beta6 was markedly suppressed,
      while mRNA expression of beta6 showed no significant variation before and after
      eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate
      the expression of beta6, without effect on beta6 mRNA expression. More
      importantly, after treated with eIF4E siRNA, cellular migratory capacity on
      fibronectin of HT-29 and beta6-transfected SW480 as well as their survival to 5
      FU was decreased distinctly. Expression of integrin beta6 could be
      translationally regulated by eIF4E, which subsequently contributed to tumor
      malignancy through enhancing cellular migration, survival, anti-apoptosis, and
      chemoresistance of colon cancer in vitro. Thus, targeting eIF4E in integrin
      alphavbeta6 expressing tumors can be a potential therapeutic strategy for
      patients with colon cancer.

PMID- 25982999
TI  - The expression of TTF-1 and Napsin A in early-stage lung adenocarcinoma
      correlates with the results of surgical treatment.
AB  - Non-small cell lung cancer (NSCLC) accounts for 80 % of lung cancers, and lung
      adenocarcinoma (ADC) is one of the main types of NSCLC. Although there are
      several studies on the relationship between lung ADC immunohistochemical
      diagnostic markers (thyroid transcription factor 1 (TTF-1) and Napsin A) and
      survival, some aspects of those studies could be improved. We examined the
      significance of the commonly used lung ADC diagnostic markers, including TTF-1,
      Napsin A, and CK7, in the prognosis of early-stage lung ADC. One hundred and
      nineteen cases of early-stage lung ADC (N0) were selected from the prospective
      database of lung cancer (Jan 2000 to Dec 2009). The expression levels of TTF-1,
      Napsin A, and CK7 in inventoried specimens were analyzed using tissue microarray
      (TMA) and immunohistochemical (IHC) analysis, and the effect of the expression
      level of each marker on patients' survival was examined. The diagnostic
      sensitivity and specificity of each marker for lung ADC were as follows: TTF-1,
      87.0 and 90.1 %; Napsin A, 72.2 and 90.4 %; and CK7, 94.6 and 76.0 %,
      respectively. Patients with high expression levels of TTF-1 and Napsin A, and
      high co-expression levels of TTF-1/Napsin A had better survival rates than those
      with low levels of expression (P < 0.05). The expression levels of CK7 were not
      related to patients' survival. Multivariate analysis showed that the expression
      levels of Napsin A and TTF-1/Napsin A are independent prognostic factors for
      survival. The IHC detection of TTF-1 and Napsin A in specimens should be
      routinely performed in postoperative early-stage lung ADC patients. Its
      significance lies not only in the differential diagnosis, but also in determining
      the prognosis.

PMID- 25983000
TI  - Differential expression and alternative splicing of cell cycle genes in imatinib
      treated K562 cells.
AB  - Cancer progression often involves the disorder of the cell cycle, and a number of
      effective chemotherapeutic drugs have been shown to induce cell cycle arrest. The
      purpose of this study was to comprehensively investigate the effects of imatinib
      on the expression profile of cell cycle genes in the chronic myeloid leukemia
      (CML) K562 cell line. In addition, we also investigated alternative splicing of
      the cell cycle genes affected by imatinib, since an important relationship has
      been shown to exist between RNA splicing and cell cycle progression. Exon array
      analysis was performed using total RNA purified from normal and imatinib-treated
      K562 cells. We identified 185 differentially expressed genes and 277 alternative
      splicing events between the two cell groups. A detailed analysis by reverse
      transcription-PCR (RT-PCR) of key genes confirmed the experimental results of the
      exon array. These results suggested that treatment of K562 cells with imatinib
      shifts the expression and alternative splicing profiles of several cell cycle
      related genes. Importantly, these findings may help improve imatinib treatment
      strategies in patients with CML and may be useful for imatinib resistance
      research and CML drug development.

PMID- 25983001
TI  - Cellular prion protein contributes to LS 174T colon cancer cell carcinogenesis by
      increasing invasiveness and resistance against doxorubicin-induced apoptosis.
AB  - As the cellular prion protein (PrP(C)) has been implicated in carcinogenesis, we
      aimed to investigate the effects of cancer cell-specific PrP(C) overexpression
      from the invasion, metastasis, and apoptosis aspects, by performing cell motility
      assays, cell proliferation assays under anchorage-dependent and anchorage
      independent conditions, and apoptosis evasion when subjected to multiple anti
      cancer drugs. Overexpression of PrP(C) in LS 174T was achieved by stable
      transfection. PrP(C) overexpression was shown to increase cell proliferation in
      anchorage-dependent and anchorage-independent manners, as shown by more viable
      cells in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay, more colonies formed in soft agar assay and increased resistance to
      anoikis in poly-2-hydroxyethyl methacrylate-coated surface. PrP(C) overexpression
      also increased cell motility and invasiveness of LS 174T. Cell adhesion to
      extracellular matrix using collagen- and fibronectin-coated surfaces revealed
      increased cell attachment in LS 174T cells overexpressing PrP(C). Analysis of
      apoptotic and necrotic cells by propidium iodide/annexin V-fluorescein
      isothiocyanate microscopy and 7-amino-actinomycin D/annexin V-phycoerythrin flow
      cytometry revealed that PrP(C) overexpression attenuated doxorubicin-induced
      apoptosis. Human apoptosis antibody array with 35 apoptosis-related proteins
      revealed that three inhibitor of apoptosis proteins (IAPs)-survivin, X-linked
      inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis
      protein-1 (cIAP-1)-were upregulated in LS 174T cells overexpressing PrP(C) in
      doxorubicin-induced apoptosis. In conclusion, the overexpression of PrP(C) could
      enhance the invasiveness and survival of LS 174T colorectal cancer cells,
      indicating that PrP(C) plays a role in colorectal cancer biology.

PMID- 25983002
TI  - Inhibition of LDHA suppresses tumor progression in prostate cancer.
AB  - A key hallmark of cancer cells is their altered metabolism, known as Warburg
      effect. Lactate dehydrogenase A (LDHA) executes the final step of aerobic
      glycolysis and has been reported to be involved in the tumor progression.
      However, the function of LDHA in prostate cancer has not been studied. In current
      study, we observed overexpression of LDHA in the clinical prostate cancer samples
      compared with benign prostate hyperplasia tissues as demonstrated by
      immunohistochemistry and real-time qPCR. Attenuated expression of LDHA by siRNA
      or inhibition of LDHA activities by FX11 inhibited cell proliferation, migration,
      invasion, and promoted cell apoptosis of PC-3 and DU145 cells. Mechanistically,
      decreased Warburg effect as demonstrated by reduced glucose consumption and
      lactate secretion and reduced expression of MMP-9, PLAU, and cathepsin B were
      found after LDHA knockdown or FX11 treatment in PC-3 and DU145 cells. Taken
      together, our study revealed the oncogenic role of LDHA in prostate cancer and
      suggested that LDHA might be a potential therapeutic target.

PMID- 25983003
TI  - Metformin use improves the survival of diabetic combined small-cell lung cancer
      patients.
AB  - Metformin has been reported having potential anticancer effect on kinds of solid
      tumors, but its role in combined small-cell lung cancer (C-SCLC) remains
      indistinct. This study aimed to explore whether metformin use has a prognosis
      benefit in diabetic C-SCLC patients. A total of 259 C-SCLC patients with diabetes
      were enrolled in our study. The clinicopathological parameters and survival data
      were collected and analyzed. The correlation between metformin use and
      clinicopathological characters was analyzed. Univariate and multivariate analyses
      were performed to investigate the prognostic significance of metformin use for C
      SCLC. The metformin was used in 120 (46.3 %) patients. Our data showed that the
      metformin use decreased C-SCLC recurrence rate (p = 0.001). The median overall
      survival (OS) and disease-free survival (DFS) were significantly better in the
      metformin use group compared to non-metformin group (OS 19.0 vs 11.5 months, p <
      0.001; DFS 10.5 vs 7.0 months, p < 0.001). Multivariate analyses indicated that
      metformin use was an independent prognostic factor for OS and DFS (p = 0.001 vs p
      = 0.018). The metformin use improved the long-term outcome of C-SCLC patients
      with diabetes, which might be considered a potential useful prognostic indicator
      and anticancer drug.

PMID- 25983004
TI  - MiR-183 promotes growth of non-small cell lung cancer cells through FoxO1
      inhibition.
AB  - Non-small cell lung cancer (NSCLC) is a prevalent cancer in lung of high
      incidence. NSCLCs often appear to be fast growing, which renders comprehension of
      the mechanisms underlying the growth of NSCLC extremely critical. Previous study
      has addressed a role of microRNA (miR) family member, miR-183, in the regulation
      of the invasiveness of NSCLC, whereas the role of miR-183 in the growth control
      of NSCLC is not clear. Here, we analyzed the regulation of FoxO1 by miR-183 in
      vitro using luciferase-reporter assay. We also analyzed the effects of miR-183 on
      NSCLC cell growth in vitro using a microculture tetrazolium (MTT) assay and in
      vivo by visualizing tumor growth using bioluminescence assay. We found that
      overexpression of miR-183 in NSCLC cells decreased FoxO1 protein levels, whereas
      inhibition of miR-183 increased FoxO1 protein levels without affecting FoxO1
      transcripts. Moreover, miR-183 bound to FoxO1 mRNA to prevent its translation
      through its 3'untranslated region (UTR). Furthermore, administration of miR-183
      suppressed FoxO1 levels in NSCLC, resulting in a significant increase in NSCLC
      growth in vitro and in vivo, while administration of antisense of miR-183
      significantly increased FoxO1 levels in NSCLC resulting in a significant decrease
      in NSCLC growth. Taken together, our data demonstrate that miR-183/FoxO1 axis may
      be a novel therapeutic target for regulating the growth of NSCLC.

PMID- 25983005
TI  - Outcomes of Platinum-Sensitive Small-Cell Lung Cancer Patients Treated With
      Platinum/Etoposide Rechallenge: A Multi-Institutional Retrospective Analysis.
AB  - Small-cell lung cancer has a high chemotherapeutic sensitivity but with
      disappointing outcome results. Patients with "sensitive disease" are those who
      respond to treatment with a long relapse-free interval (RFI): in these cases
      rechallenge with first-line chemotherapy might represent a therapeutic
      opportunity. Our largest retrospective experience confirmed that rechallenge is
      feasible with interesting outcome results; there are no statistical differences
      between RFI and outcome. INTRODUCTION: Patients with small-cell lung cancer
      (SCLC) that progresses after first-line (FL) chemotherapy have a poor prognosis
      and second-line (SL) chemotherapy has limited efficacy. Patients whose disease
      relapses/progresses > 90 days after FL platinum-based treatment are considered
      platinum-sensitive and could be rechallenged with a similar regimen. We conducted
      a multicenter retrospective analysis to evaluate outcomes of SCLC patients
      rechallenged with platinum/etoposide. PATIENTS AND METHODS: Records of all SCLC
      patients treated in 7 institutions between January 2007 and December 2011 were
      reviewed. The primary end point was overall survival from the time of rechallenge
      (OS-R); secondary end points were progression-free survival (PFS) and overall
      survival from the time of diagnosis (OS-D). Survival curves were calculated using
      the Kaplan-Meier method. RESULTS: Of the 2000 SCLC patients identified, 112
      (5.6%) had sensitive disease treated with rechallenge platinum/etoposide; 65%
      were men with a median age of 64 years. At the time of diagnosis, 44% of patients
      had limited disease, 82% had an Eastern Cooperative Oncology Group performance
      status of 0 to 1. A median of 4 cycles of rechallenge was administered. Tumor
      response was 3% for complete response and 42% for partial response, 19% of
      patients maintained stable disease, 27% progressive disease, and 9% were not
      evaluable. Median PFS from the time of rechallenge was 5.5 months (95% confidence
      interval [CI], 4.4-6.3). Median OS-R and OS-D were 7.9 months (95% CI, 6.9-9.7)
      and 21.4 months (95% CI, 19.8-24.1), respectively. Subgroup analysis according to
      relapse-free interval (90-119 vs. 120-149 vs. > 150 days) did not show any
      statistically significant difference in PFS or OS-R. CONCLUSION: The outcome for
      SL chemotherapy for SCLC is poor. Rechallenge platinum/etoposide is a reasonable
      option with potentially better outcomes than standard chemotherapy.

PMID- 25983006
TI  - Shared Decision Making in Pediatrics: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Little is known about the impact of interventions to support shared
      decision making (SDM) with pediatric patients. OBJECTIVES: To summarize the
      efficacy of SDM interventions in pediatrics on patient-centered outcomes. DATA
      SOURCES: We searched Ovid Medline, Ovid Embase, Ovid Cochrane Library, Web of
      Science, Scopus, and Ovid PsycInfo from database inception to December 30, 2013,
      and performed an environmental scan. STUDY ELIGIBILITY CRITERIA: We included
      interventions designed to engage pediatric patients, parents, or both in a
      medical decision, regardless of study design or reported outcomes. STUDY
      APPRAISAL AND SYNTHESIS METHODS: We reviewed all studies in duplicate for
      inclusion, data extraction, and risk of bias assessment. Meta-analysis was
      performed on 3 outcomes: knowledge, decisional conflict, and satisfaction.
      RESULTS: Sixty-one citations describing 54 interventions met eligibility
      criteria. Fifteen studies reported outcomes such that they were eligible for
      inclusion in meta-analysis. Heterogeneity across studies was high. Meta-analysis
      revealed SDM interventions significantly improved knowledge (standardized mean
      difference [SMD] 1.21, 95% confidence interval [CI] 0.26 to 2.17, P = .01) and
      reduced decisional conflict (SMD -1.20, 95% CI -2.01 to -0.40, P = .003).
      Interventions showed a nonsignificant trend toward increased satisfaction (SMD
      0.37, 95% CI -0.04 to 0.78, P = .08). LIMITATIONS: Included studies were
      heterogeneous in nature, including their conceptions of SDM. CONCLUSIONS AND
      IMPLICATIONS OF KEY FINDINGS: A limited evidence base suggests that pediatric SDM
      interventions improve knowledge and decisional conflict, but their impact on
      other outcomes is unclear. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO
      CRD42013004761
      (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004761).

PMID- 25983007
TI  - PROTEOMIC ANALYSIS OF UBIQUITINATED PROTEINS FROM DELTAMETHRIN-RESISTANT AND
      SUSCEPTIBLE STRAINS OF THE DIAMONDBACK MOTH, Plutella Xylostella L.
AB  - Ubiquitin, a small protein consisting of 76 amino acids, acts in protein
      degradation, DNA repair, signal transduction, transcriptional regulation, and
      receptor control through endocytosis. Using proteomics, we compared the
      differentially ubiquitinated proteins between a deltamethrin-resistant (DR)
      strain and a deltamethrin-sensitive (DS) strain in third-instar larvae of the
      diamondback moth. We used polyubiquitin affinity beads to enrich ubiquitinated
      proteins and then performed one-dimensional SDS-PAGE separation and mass
      spectrometric identification. In the DR strain, We found 17 proteins that were
      upregulated (relative to the DS strain), including carbonic anhydrase family
      members, ADP ribosylation factor 102F CG11027-PA, protein kinase 61C,
      phospholipase A2 , dihydrolipoamide dehydrogenase, tyrosine hydroxylase, and heat
      shock proteins, and five proteins that were downregulated in the DS strain,
      including carboxylesterase and DNA cytosine-5 methyltransferase. These results
      were also verified by qPCR. The differentially ubiquitinated proteins/enzymes
      were mainly responsible for protein binding, catalytic activity, and molecular
      transducer activity. These results improve our understanding of the relationship
      between protein ubiquitination and the deltamethrin stress response. 

PMID- 25983008
TI  - The Relationship Between Level of Adherence to Automatic Wireless Remote
      Monitoring and Survival in Pacemaker and Defibrillator Patients.
AB  - BACKGROUND: Remote monitoring (RM) technology embedded within cardiac rhythm
      devices permits continuous monitoring, which may result in improved patient
      outcomes. OBJECTIVES: This study used "big data" to assess whether RM is
      associated with improved survival and whether this is influenced by the type of
      cardiac device and/or its degree of use. METHODS: We studied 269,471 consecutive
      U.S. patients implanted between 2008 and 2011 with pacemakers (PMs), implantable
      cardioverter-defibrillators (ICDs), or cardiac resynchronization therapy (CRT)
      with pacing capability (CRT-P)/defibrillation capability (CRT-D) with wireless
      RM. We analyzed weekly use and all-cause survival for each device type by the
      percentage of time in RM (%TRM) stratified by age. Socioeconomic influences on
      %TRM were assessed using 8 census variables from 2012. RESULTS: The group had
      implanted PMs (n = 115,076; 43%), ICDs (n = 85,014; 32%), CRT-D (n = 61,475;
      23%), and CRT-P (n = 7,906; 3%). When considered together, 127,706 patients (47%)
      used RM, of whom 67,920 (53%) had >=75%TRM (high %TRM) and 59,786 (47%) <75%TRM
      (low %TRM); 141,765 (53%) never used RM (RM None). RM use was not affected by age
      or sex, but demonstrated wide geographic and socioeconomic variability. Survival
      was better in high %TRM versus RM None (hazard ratio [HR]: 2.10; p < 0.001), in
      high %TRM versus low %TRM (HR: 1.32; p < 0.001), and also in low %TRM versus RM
      None (HR: 1.58; p < 0.001). The same relationship was observed when assessed by
      individual device type. CONCLUSIONS: RM is associated with improved survival,
      irrespective of device type (including PMs), but demonstrates a graded
      relationship with the level of adherence. The results support the increased
      application of RM to improve patient outcomes.

PMID- 25983009
TI  - Remote Monitoring of Implantable Cardioverter-Defibrillators: A Systematic Review
      and Meta-Analysis of Clinical Outcomes.
AB  - BACKGROUND: Remote monitoring (RM) of implantable cardioverter-defibrillators
      (ICD) is an established technology integrated into clinical practice. One recent
      randomized controlled trial (RCT) and several large device database studies have
      demonstrated a powerful survival advantage for ICD patients undergoing RM
      compared with those receiving conventional in-office (IO) follow-up. OBJECTIVES:
      This study sought to conduct a systematic published data review and meta-analysis
      of RCTs comparing RM with IO follow-up. METHODS: Electronic databases and
      reference lists were searched for RCTs reporting clinical outcomes in ICD
      patients who did or did not undergo RM. Data were extracted from 9 RCTs,
      including 6,469 patients, 3,496 of whom were randomized to RM and 2,973 to IO
      follow-up. RESULTS: In the RCT setting, RM demonstrated clinical outcomes
      comparable with office follow-up in terms of all-cause mortality (odds ratio
      [OR]: 0.83; p = 0.285), cardiovascular mortality (OR: 0.66; p = 0.103), and
      hospitalization (OR: 0.83; p = 0.196). However, a reduction in all-cause
      mortality was noted in the 3 trials using home monitoring (OR: 0.65; p = 0.021)
      with daily verification of transmission. Although the odds of receiving any ICD
      shock were similar in RM and IO patients (OR: 1.05; p = 0.86), the odds of
      inappropriate shock were reduced in RM patients (OR: 0.55; p = 0.002).
      CONCLUSIONS: Meta-analysis of RCTs demonstrates that RM and IO follow-up showed
      comparable overall outcomes related to patient safety and survival, with a
      potential survival benefit in RCTs using daily transmission verification. RM
      benefits include more rapid clinical event detection and a reduction in
      inappropriate shocks.

PMID- 25983010
TI  - Remote Monitoring and Outcomes in Pacemaker and Defibrillator Patients: Big Data
      Saving Lives?

PMID- 25983011
TI  - Social living mitigates the costs of a chronic illness in a cooperative
      carnivore.
AB  - Infection risk is assumed to increase with social group size, and thus be a cost
      of group living. We assess infection risk and costs with respect to group size
      using data from an epidemic of sarcoptic mange (Sarcoptes scabiei) among grey
      wolves (Canis lupus). We demonstrate that group size does not predict infection
      risk and that individual costs of infection, in terms of reduced survival, can be
      entirely offset by having sufficient numbers of pack-mates. Infected individuals
      experience increased mortality hazards with increasing proportions of infected
      pack-mates, but healthy individuals remain unaffected. The social support of
      group hunting and territory defence are two possible mechanisms mediating
      infection costs. This is likely a common phenomenon among other social species
      and chronic infections, but difficult to detect in systems where infection status
      cannot be measured continuously over time. 

PMID- 25983012
TI  - Three dimensional graphene based materials: Synthesis and applications from
      energy storage and conversion to electrochemical sensor and environmental
      remediation.
AB  - With superior electrical/thermal conductivities and mechanical properties, two
      dimensional (2D) graphene has become one of the most intensively explored carbon
      allotropes in materials science. To exploit the inherent properties fully, 2D
      graphene sheets are often fabricated or assembled into functional architectures
      (e.g. hydrogels, aerogels) with desired three dimensional (3D) interconnected
      porous microstructures. The 3D graphene based materials show many excellent
      characteristics including increased active material per projected area,
      accessible mass transport or storage, electro/thermo conductivity,
      chemical/electrochemical stability and flexibility. It has paved the way for
      practical requirements in electronics, adsorption as well as catalysis related
      system. This review shows an extensive overview of the main principles and the
      recent synthetic technologies about fabricating various innovative 3D graphene
      based materials. Subsequently, recent progresses in electrochemical energy
      devices (lithium/lithium ion batteries, supercapacitors, fuel cells and solar
      cells) and hydrogen energy generation/storage are explicitly discussed. The up to
      date advances for pollutants detection and environmental remediation are also
      reviewed. Finally, challenges and outlooks in materials development for energy
      and environment are suggested. 

PMID- 25983014
TI  - The role of rhinovirus in children hospitalized for acute respiratory disease,
      Santa Fe, Argentina.
AB  - Human rhinoviruses (HRVs) were historically considered upper airway pathogens.
      However, they have recently been proven to cause infections in the lower
      respiratory tract, resulting in hospitalization of children with pneumonia,
      bronchiolitis, and chronic pulmonary obstruction. In this report, HRV frequency
      and seasonality are described together with patient clinical-epidemiological
      aspects. From a total of 452 surveyed samples, the HRV nucleic acids was detected
      in 172 (38.1%) and found in every month of the study year. 60% of inpatients with
      acute respiratory infection (ARI) associated with HRV were under 6 months of age
      and 31% had a clinical history, being preterm birth and recurrent wheezing the
      prevailing conditions. The most frequent discharge diagnoses were pneumonia
      (35.2%), bronchiolitis (32.4%), and bronchitis (12.4%). Fifteen point nine
      percent of patients required admission into intensive care units. The results
      obtained in this study demonstrated the association between HRV and children
      hospitalizations caused by ARI.

PMID- 25983013
TI  - The influence of partnership on contraceptive use among HIV-infected women
      accessing antiretroviral therapy in rural Uganda.
AB  - OBJECTIVE: The objective was to determine individual and dyadic factors
      associated with effective contraceptive use among human immunodeficiency virus
      (HIV)-infected women accessing antiretroviral therapy (ART) in rural Uganda.
      STUDY DESIGN: HIV-infected women enrolled in the Uganda AIDS Rural Treatment
      Outcomes cohort completed questionnaires (detailing sociobehavioral
      characteristics, sexual and reproductive history, contraceptive use, fertility
      desires) and phlebotomy (October 2011-March 2013). We describe prevalence of
      effective contraceptive use (i.e., consistent condom use and/or oral
      contraceptives, injectable hormonal contraception, intrauterine device, female
      sterilization) in the previous 6 months among sexually active, nonpregnant women
      (18-40 years). We assessed covariates of contraceptive use using multivariable
      logistic regression. RESULTS: A total of 362 women (median values: age 30 years,
      CD4 count 397 cells/mm(3), 4.0 years since ART initiation) were included. Among
      284 sexually active women, 50% did not desire a(nother) child, and 51% had a
      seroconcordant partner. Forty-five percent (n=127) reported effective
      contraceptive use, of whom 57% (n=72) used condoms, 42% (n=53) injectables, 12%
      (n=15) oral contraceptives and 11% (n=14) other effective methods. Dual
      contraception was reported by 6% (n=8). Only "partnership fertility desire" was
      independently associated with contraceptive use; women who reported that neither
      partner desired a child had significantly increased odds of contraceptive use
      (adjusted odds ratio: 2.40, 95% confidence interval: 1.07-5.35) compared with
      women in partnerships where at least one partner desired a child. CONCLUSIONS:
      Less than half of sexually active HIV-infected women accessing ART used effective
      contraception, of which 44% (n=56) relied exclusively on male condoms,
      highlighting a continued need to expand access to a wider range of longer-acting
      female-controlled contraceptive methods. Association with partnership fertility
      desire underscores the need to include men in reproductive health programming.
      IMPLICATIONS STATEMENT: Less than half of sexually active HIV-infected women
      accessing ART in rural Uganda reported using effective contraception, of whom 44%
      relied exclusively on the male condom. These findings highlight the need to
      expand access to a wider range of longer-acting, female-controlled contraceptive
      methods for women seeking to limit or space pregnancies. Use of contraception was
      more likely when both the male and female partner expressed concordant desires to
      limit future fertility, emphasizing the importance of engaging men in
      reproductive health programming.

PMID- 25983015
TI  - Trends in stroke admissions to a Tanzanian hospital over four decades: a
      retrospective audit.
AB  - AIMS: The aim of this study was to record stroke admissions to a tertiary
      referral hospital in Tanzania over four decades. METHODS: We audited the medical
      records held at a large teaching and tertiary referral hospital in northern
      Tanzania over four decades. We collected records for the years 1974-1976, 1984
      1986, 1994-1995 and 2008. All patients admitted as inpatients with a primary
      diagnosis of stroke were included in the study. Data collected included age, sex,
      stroke subtype, predominant side of symptoms and survival to discharge. RESULTS:
      The number of stroke admissions rose from just four in the three-year period 1974
      1976 (mean 1.3 cases annually) to 153 cases annually in 2008. The mean age of
      those admitted rose steadily during this period, as did the proportion of females
      admitted. CONCLUSIONS: The burden of stroke on health services in Tanzania
      appears to have increased rapidly. If this increase is to be slowed, then
      sustainable primary preventative measures to target known stroke risk factors
      will be required.

PMID- 25983016
TI  - Successful treatment of Bowen's disease with ingenol mebutate 0.05% gel.

PMID- 25983017
TI  - In vitro effects induced by diesel exhaust at an air-liquid interface in a human
      lung alveolar carcinoma cell line A549.
AB  - The present study examined the effects induced in vitro in human adenocarcinoma
      derived alveolar basal epithelial A549 cells by diesel particulate matter (DPM)
      administered into the culture medium or by diesel exhaust administered at an air
      liquid interface. When A549 cells were exposed to DPM in the culture medium, cell
      proliferation was inhibited at doses of 10-100 MUg/mL; generation of interleukin
      (IL)-8 and the antioxidant enzyme, heme oxygenase-1 (HO-1), were inhibited at a
      dose of 100 MUg/mL, and hydroxyl radicals were produced, but could be inhibited
      by catalase or superoxide dismutase. In contrast, when A549 cells were exposed to
      diesel exhaust, cell proliferation was inhibited in the absence, but not in the
      presence, of a diesel particulate filter (DPF); in the absence of a DPF IL-8 was
      produced in the same amount as in the control cells but was suppressed in the
      presence of a DPF; HO-1 mRNA was transiently over-expressed in the presence of a
      DPF, and it was also increased slightly produced in the absence of a DPF but
      statistically not significant in the presence of a DPF, and it was also increased
      slightly produced in the absence of a DPF but statistically not significant; HO-1
      was transiently produced independent of the absence or the presence of a DPF; and
      hydroxyl radicals were weakly produced, even in the presence of a DPF but could
      be inhibited by catalase or superoxide dismutase. It is thus suggested that
      oxidative stress may be induced by exposure to DPM or diesel exhaust and thereby
      exerts cytotoxic effect. The introduction of a DPF is effective to protect cells
      from the toxicity of diesel exhaust presumably by suppression of an oxidative
      stress.

PMID- 25983018
TI  - Sex-related neurogenesis decrease in hippocampal dentate gyrus with depressive
      like behaviors in sigma-1 receptor knockout mice.
AB  - Male sigma-1 receptor knockout (sigma1R(-/-)) mice showed depressive-like
      phenotype with deficit in the survival of newly generated neuronal cells in the
      hippocampal dentate gyrus (DG), but female sigma1R(-/-) mice did not. The level
      of serum estradiol (E2) at proestrus or diestrus did not differ between female
      sigma1R(-/-) mice and wild-type (WT) mice. Ovariectomized (OVX) female sigma1R(-/
      ) mice, but not WT mice, presented the same depressive-like behaviors and
      neurogenesis decrease as male sigma1R(-/-) mice. Treatment of male sigma1R(-/-)
      mice with E2 could alleviate the depressive-like behaviors and rescue the
      neurogenesis decrease. In addition, E2 could correct the decline in the density
      of NMDA-activated current (INMDA) in granular cells of DG and the phosphorylation
      of NMDA receptor (NMDAr) subtype 2B (NR2B) in male sigma1R(-/-) mice, which was
      associated with the elevation of Src phosphorylation. The neuroprotection and
      antidepressant effects of E2 in male sigma1R(-/-) mice were blocked by the
      inhibitor of Src or NR2B. The NMDAr agonist showed also the neuroprotection and
      antidepressant effects in male sigma1R(-/-) mice, which were insensitive to the
      Src inhibitor. On the other hand, either the deprivation of E2 or the inhibition
      of Src in female sigma1R(-/-) mice rather than WT mice led to a distinct decline
      in INMDA and NR2B phosphorylation. Similarly, the Src inhibitor could cause
      neurogenesis decrease and depressive-like behaviors in female sigma1R(-/-) mice,
      but not in WT mice. These results indicate that the sigma1R deficiency impairs
      neurogenesis leading to a depressive-like phenotype, which is alleviated by the
      neuroprotection of E2. 

PMID- 25983020
TI  - Activation of GABA-A receptors during postnatal brain development increases
      anxiety- and depression-related behaviors in a time- and dose-dependent manner in
      adult mice.
AB  - Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during
      postnatal development can have long-lasting consequences for later life behavior,
      like the individual's response to stress. However, it is unclear which postnatal
      windows of sensitivity to GABA-ergic modulations are associated with what later
      life behavioral outcomes. Therefore, we sought to determine whether neonatal
      activation of the GABA-A receptor during two postnatal periods, an early window
      (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety-
      and depression-related behaviors in male mice in later life. To this end, mice
      were treated with either saline or muscimol (50, 100, 200, 300 and 500MUg/kg)
      during the early and late postnatal periods. An additional group of mice was
      treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to
      adulthood male mice were exposed to behavioral tests to measure anxiety- and
      depression-related behaviors. Baseline and stress-induced corticosterone (CORT)
      levels were also measured. The results indicate that early postnatal and to a
      lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol
      increased anxiety-like behavior and stress-induced CORT levels in adults.
      Moreover, the early postnatal treatment with muscimol increased depression-like
      behavior with increasing baseline CORT levels. The anxiogenic and depression-like
      later-life consequences could be antagonized by bicuculline. Our findings suggest
      that GABA-A receptor signaling during early-life can influence anxiety- and
      depression-related behaviors in a time- and dose-dependent manner in later life.
      Our findings help to increase insight in the developmental mechanisms
      contributing to stress-related disorders. 

PMID- 25983019
TI  - Prefrontal cortical GABA abnormalities are associated with reduced hippocampal
      volume in major depressive disorder.
AB  - Hippocampal volume reduction has been related to treatment-resistant depression
      (TRD) and is hypothesized to reflect impaired amino-acid neurotransmission. To
      better understand the role of amino acid neurotransmission in hippocampal volume
      deficits, and subsequent resistance to treatment, this study investigated the
      relationship between hippocampal volumes and GABA levels in the anterior
      cingulate cortex (ACC), previously associated with TRD. Thirty-three medication
      free major depressive disorder (MDD; 14 TRD and 19 non-TRD) and 26 healthy
      controls (HC) subjects were studied. Participants underwent high-resolution
      magnetic resonance imaging (MRI) to estimate hippocampal volume and proton MR
      spectroscopy ((1)H MRS) to measure ACC GABA levels. MDD patients, with known ACC
      GABA levels, were divided into two groups: MDD Low GABA and MDD High GABA. We
      found a significant reduction in hippocampal volume in the MDD Low GABA group
      compared to MDD High GABA (p<0.001) and HC (p=0.01). The relationship between
      hippocampal volume and cortical GABA was population (i.e. MDD group) and region
      specific (i.e. prefrontal cortex). Comparing TRD, non-TRD and HC groups, there
      was a main effect of group on hippocampal volume (p=0.04), which post hoc
      analysis revealed as smaller hippocampal volume in TRD subjects than in non-TRD
      (p=0.05) and HC groups (p=0.03). No hippocampal volume differences between non
      TRD and HC groups. The data provides insight into the role of prefrontal
      neurochemical deficits in the limbic structural abnormalities observed in MDD. In
      addition, it replicates the relationship between TRD and smaller hippocampal
      volumes. 

PMID- 25983021
TI  - Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy
      in patients with curatively resected stage II or III colon cancer (JFMC41-1001
      C2: JOIN trial).
AB  - PURPOSE: Adjuvant FOLFOX is a widely accepted standard therapy for resected colon
      cancer. The incidence of grade 3-4 peripheral sensory neuropathy (PSN) was 12.4
      and 5.7 % in the MOSAIC and Eastern MASCOT trials, while that of grade 3-4
      allergic reactions (AR) was 2.9 and 3.1 %, respectively. The JFMC41-1001-C2 trial
      (JOIN trial) investigated the tolerability of modified FOLFOX6 (mFOLFOX6) in
      Japanese colon cancer patients. METHODS: Twelve cycles of mFOLFOX6 were given to
      patients with the same eligibility criteria as in the MOSAIC study: stage II or
      III curatively resected colon cancer, performance status of 0-1, aged 20 years or
      older, starting mFOLFOX6 within 7 weeks of surgery, and adequate organ function.
      The primary endpoints were the incidence of PSN persisting for >=8 days that
      interfered with daily activities and the incidence of grade 3-4 AR. The target
      sample size was 800. RESULTS: From November 2010 to March 2012, 882 patients were
      enrolled at 198 institutions. Safety was analyzed in 828 patients with finalized
      data out of 848 patients receiving mFOLFOX6. The incidence of PSN persisting >=8
      days was 3.3 % [95 % confidence interval (CI) 2.2-4.7], while that of grade 3-4
      AR was 1.7 % (95 % CI 0.9-2.8). The treatment completion rate was 67.0 %. The
      median total dosage of oxaliplatin was 811.1 mg/m(2). The overall incidence of
      grade 3-4 PSN was 5.8 %. Interstitial pneumonitis occurred in one patient. There
      were no treatment-related deaths. CONCLUSIONS: Adjuvant mFOLFOX6 is tolerable for
      Japanese patients with colon cancer.

PMID- 25983022
TI  - Double-blind, placebo-controlled, randomized phase II study of TJ-14
      (Hangeshashinto) for infusional fluorinated-pyrimidine-based colorectal cancer
      chemotherapy-induced oral mucositis.
AB  - PURPOSE: Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of
      prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy
      induced oral mucositis (COM). We conducted a double-blind, placebo-controlled,
      randomized comparative trial to investigate whether TJ-14 prevents and controls
      COM in patients with colorectal cancer. METHODS: Ninety-three patients with
      colorectal cancer who developed moderate-to-severe COM (WHO grade ?1) during any
      cycle of chemotherapy using FOLFOX, FOLFIRI, and/or XELOX treatment were randomly
      assigned to receive either TJ-14 (n = 46) or placebo (n = 47). Patients received
      the administration of placebo or TJ-14 for 2 weeks at the start of the next
      course of chemotherapy. Patients were assessed three times per week for safety
      and for COM incidence and its severity using the WHO grading. RESULTS: Ninety
      eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were
      included in the analysis after the key-opening. Although the incidence of grade
      ?2 oral mucositis was lower for patients treated with TJ-14 compared to those
      treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p =
      0.41). The median duration of grade ?2 mucositis was 5.5 versus 10.5 days (p =
      0.018). No difference in other treatment toxicity was observed between the two
      groups, and patients exhibited high compliance in dosing administration.
      CONCLUSION: The present study results did not meet the primary endpoint. However,
      TJ-14 demonstrated a significant effect in the treatment of grade ?2 mucositis in
      patients with colorectal cancer compared to the placebo.

PMID- 25983024
TI  - Examination of the double-deficit hypothesis with adolescents and young adults
      with dyslexia.
AB  - The double-deficit hypothesis (DDH) of the developmental dyslexias (Wolf and
      Bowers, Journal of Educational Psychology, 91, 415-438, 1999) was investigated
      with 149 adolescents and young adults (age range = 16 to 24 years) with dyslexia.
      Confirmatory factor analysis indicated that a two-factor model with separate
      naming speed (NS) and phonological awareness (PA) constructs was superior to a
      one-factor model, supporting the assumption within the DDH that NS is a source of
      reading dysfunction separable from PA. Hierarchical multiple regression analyses
      resulted in findings that were only partially supportive of the DDH. NS was
      predictive of word reading, spelling, and reading fluency beyond PA and verbal
      intellectual ability, but not pseudoword reading and timed and untimed reading
      comprehension. Examination of DDH subtypes did not support the core assumption of
      the DDH that the double-deficit subtype would have more impaired reading skills
      than both of the single-deficit subtypes. The NS deficit subtype was found to be
      more prevalent than the double-deficit and PA deficit subtypes within the
      subgroup of dyslexics with impairment in reading fluency. Overall results
      provided mixed support for the DDH and pointed to the need for the inclusion of
      additional abilities within theories of the underlying mechanisms disrupted in
      dyslexia.

PMID- 25983023
TI  - Association of fludarabine pharmacokinetic/dynamic biomarkers with donor
      chimerism in nonmyeloablative HCT recipients.
AB  - PURPOSE: Fludarabine monophosphate (fludarabine) is an integral component of many
      reduced-intensity conditioning regimens for hematopoietic cell transplantation
      (HCT). Fludarabine's metabolite, 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara
      A), undergoes cellular uptake and activation to form the active cytotoxic
      metabolite fludarabine triphosphate (F-ara-ATP), which inhibits cellular DNA
      synthesis in CD4(+) and CD8(+) cells. In this study, we evaluated whether
      fludarabine-based pharmacologic biomarkers were associated with clinical outcomes
      in HCT recipients. METHODS: Participants with hematologic diseases were
      conditioned with fludarabine and low-dose total body irradiation (TBI) followed
      by allogeneic HCT and post-grafting immunosuppression. After fludarabine
      administration, we evaluated pharmacological biomarkers for fludarabine-F-ara-A
      area under the curve (AUC) and the ratio of circulating CD4(+) and CD8(+) cells
      (CD4(+)/CD8(+) ratio) after fludarabine administration-in 102 patients; F-ara-ATP
      accumulation rate in enriched CD4(+) and CD8(+) cells was evaluated in 36 and 34
      patients, respectively. RESULTS: Interpatient variability in the pharmacological
      biomarkers was high, ranging from 3.7-fold (F-ara-A AUC) to 39-fold (F-ara-ATP in
      CD8(+) cells). Circulating CD8(+) cells were more sensitive to fludarabine
      administration. A population pharmacokinetic-based sampling schedule successfully
      allowed for estimation of F-ara-A AUC in this outpatient population. There was a
      poor correlation between the F-ara-AUC and the F-ara-ATP accumulation rate in
      CD4(+) (R (2) = 0.01) and CD8(+) cells (R (2) = 0.00). No associations were seen
      between the four biomarkers and clinical outcomes (day +28 donor T cell
      chimerism, acute graft-versus-host disease (GVHD), neutrophil nadirs,
      cytomegalovirus reactivation, chronic GVHD, relapse, non-relapse mortality, or
      overall mortality). CONCLUSIONS: Considerable interpatient variability exists in
      pharmacokinetic and fludarabine-based biomarkers, but these biomarkers are not
      associated with clinical outcomes in fludarabine/TBI-conditioned patients.

PMID- 25983025
TI  - Routes of drug delivery into the nail apparatus: Implications for the efficacy of
      topical nail solutions in onychomycosis.
AB  - The route of antifungal drug entry into the nail plate and the underlying nail
      bed plays an important role in determining the efficacy of therapy. Oral
      antifungal agents reach the nail bed and nail plate by being ingested and
      achieving antifungal levels in the blood stream that are well in excess of the
      minimum inhibitory concentration. The reticular circulation at the distal end of
      the digit enables the drug to reach the nail bed, the proximal matrix and the
      lateral nail folds. The drug then diffuses into the proximal, ventral and lateral
      nail plate. The primary route of drug delivery for topical lacquers is
      transungual, with drug applied to the dorsal aspect of the nail plate and
      penetrating to the underlying nail bed. The new topical agents approved in the US
      for the treatment of onychomycosis are solutions with lower viscosity and
      increased nail penetration characteristics; therefore, these agents penetrate
      through the transungual route, but also through the space between the nail plate
      and the nail bed. This subungual route is an important method of drug delivery
      and is able to in part circumvent the thickness of the nail plate. 

PMID- 25983026
TI  - First use of an expandable sheath and transcaval access for transcatheter Edwards
      SAPIEN 3 aortic valve implantation.
AB  - AIMS: We aimed to describe the first percutaneous transcaval TAVI in Europe using
      the expandable introducer sheath (eSheath; Edwards Lifesciences, Irvine, CA, USA)
      for implantation of an Edwards SAPIEN 3 aortic valve (23 mm). METHODS AND
      RESULTS: A 72-year-old male patient presented with dyspnoea (NYHA III) in part
      due to severe aortic stenosis. Concomitant diseases were severe peripheral artery
      disease, severe chronic obstructive pulmonary disease (GOLD IV) and renal
      insufficiency, such that neither a transfemoral nor a transapical approach was
      considered favourable. An eSheath was introduced into the abdominal aorta via the
      femoral vein and the inferior vena cava. TAVI was then performed according to
      standard procedures. After TAVI, the veno-arterial junction was occluded with a 6
      mm AMPLATZER Muscular VSD Occluder (St. Jude Medical, St. Paul, MN, USA) using an
      8.5 Fr AgilisTM sheath (St. Jude Medical) inside the TAVI sheath. Aortography
      showed no retroperitoneal accumulation of contrast media. The femoral vein access
      site was closed using two prepositioned sutures (ProGlide; Abbott Vascular, Santa
      Clara, CA, USA). A CT scan the following day showed no retroperitoneal
      haemorrhage. CONCLUSIONS: Percutaneous transcaval venous access to the aorta may
      provide a new access strategy for TAVI in otherwise ineligible patients and
      appears safe with expandable sheath technology.

PMID- 25983027
TI  - First-in-man evaluation of the novel balloon delivery system STENTYS Xposition S
      for the self-apposing coronary artery stent: impact on longitudinal geographic
      miss during stenting.
AB  - AIMS: A novel balloon delivery system (BDS) for the self-apposing STENTYS
      sirolimus-eluting stent (SES) has been developed for highly precise longitudinal
      stent positioning and deployment. The aim of this first-in-man study is to report
      the quantitative coronary analysis (QCA) angiography and optical coherence
      tomography (OCT) results as well as the 30-day clinical outcomes of the STENTYS
      Xposition S SES. METHODS AND RESULTS: We included 25 patients (mean age 66.1+/
      10.7 years) with stable coronary artery disease (24%) or acute coronary syndrome
      (including STEMI in 40%). The device was successfully placed at the intended site
      in all cases (100%), without procedural complications. Longitudinal geographic
      miss (entire lesion length [on QCA] not completely covered by the stent) was not
      observed. Pre-procedural MLD on QCA was 1.30+/-0.74 mm and post-procedural MLD
      was 2.74+/-0.44 mm, p<0.001 (acute gain 1.44+/-0.70 mm). OCT analyses showed a
      low percentage of malapposed stent struts directly post stent placement (2.4%),
      which further decreased after post-dilatation (0.6%, p=0.013), while mean stent
      area increased (from 9.7 mm2 to 10.5 mm2, p<0.001). At 30-day clinical follow-up,
      one (4%) major adverse cardiac event (MACE) was observed. One acute stent
      thrombosis (ST) occurred immediately post procedure in a STEMI patient which was
      related to inadequate medication therapy. CONCLUSIONS: This first-in-man study
      demonstrated that the use of the novel STENTYS Xposition S balloon delivery
      system is feasible with a high technical success rate without longitudinal
      geographical miss. Stent strut malapposition rate directly after STENTYS
      placement was low and improved further after post-dilatation.

PMID- 25983028
TI  - Thirty-day VARC-2 and performance data of a new self-expanding transcatheter
      aortic heart valve.
AB  - AIMS: Transcatheter aortic valve therapy has become an established procedure for
      patients at high risk for surgical valve replacement. The BIOVALVE-I study aims
      to assess the safety and performance of a novel self-expanding transcatheter
      heart valve. METHODS AND RESULTS: In this prospective, single-centre, first-in
      human study, 13 patients with severe aortic stenosis suitable for transfemoral
      transcatheter aortic valve implantation were enrolled. Mean logistic EuroSCORE
      was 14.4+/-3.7% and mean STS PROM score was 4.3+/-1.6%. The primary endpoint, 30
      day early safety composite per VARC-2, was observed in two patients (15.4%, one
      life-threatening bleeding and one valve-in-valve procedure). The implant was
      aborted in two patients due to unsuitable aortic anatomy. Overall, device success
      was obtained in nine patients (69.2%, two aborted implants, one valve-in-valve
      procedure and one patient with moderate aortic regurgitation). As determined by
      an independent core laboratory, all but one patient had less than moderate total
      aortic regurgitation at 30-day follow-up, mean aortic gradient was 6.7+/-2.3 mmHg
      and effective orifice area 1.8+/-0.3 cm. Pacemakers were implanted in three
      patients (23.1%), and no death, stroke, myocardial infarction or acute kidney
      failure was observed. CONCLUSIONS: In this first-in-human study, the feasibility
      of implantation of the BIOVALVE system and its re-sheathing functionality was
      demonstrated, and short-term safety data were encouraging. Larger studies are
      required to confirm the performance of the device.

PMID- 25983030
TI  - Lipase-modified pH-responsive microgel-based optical device for triglyceride
      sensing.
AB  - Lipase-modified pH-responsive poly(N-isopropylacrylamide)-based microgels were
      synthesized. An optical device was subsequently fabricated by sandwiching the
      enzyme loaded responsive microgels between two thin Au layers, and their response
      to triolein, a model triglyceride, was investigated. The device's response
      depended on the triglyceride concentration, demonstrating its potential
      application as a triglyceride biosensor. 

PMID- 25983029
TI  - Genome-wide Survey of Runs of Homozygosity Identifies Recessive Loci for Bone
      Mineral Density in Caucasian and Chinese Populations.
AB  - Runs of homozygosity (ROHs), in which both parental alleles are identical, have
      been proposed to have recessive effects on multiple human complex diseases.
      Osteoporosis is a common complex disease characterized by low bone mineral
      density (BMD), which is highly heritable. And recessive loci that contribute to
      BMD variations have been identified. In this study, we performed a genome-wide
      ROHs association study using our SNP array data from three GWAS samples including
      4,900 subjects from Caucasian and Chinese populations. Significant results were
      further subjected to replication in 3,747 additional subjects. ROHs associated
      with BMD were also tested for associations with osteoporotic fractures in a GWAS
      fracture sample. Combining results from all the samples, we identified 697
      autosomal regions with ROHs. Among these, we detected genome-wide significant
      associations between BMD and 6 ROHs, including ROH1q31.3, 1p31.1, 3q26.1,
      11q12.1, 21q22.1 and 15q22.3 (combined P = 6.29 * 10(-5)-3.17 * 10(-8)).
      Especially, ROH1p31.1 was found to be associated with increased risk of
      osteoporotic hip fractures (odds ratio [OR] = 3.71, P = 0.032). To investigate
      the functional relevance of the identified ROHs, we performed cis-expression
      quantitative trait locus (eQTL) analysis in lymphoblast cell lines. Three ROHs,
      including ROH1p31.1, 11q12.1, and 15q22.3, were found to be significantly
      associated with mRNA expression levels of their nearby genes (PeQTL < 0.05). In
      summary, our findings reveal that ROHs could play as recessive-acting
      determinants contributing to the pathogenesis of osteoporosis. Further molecular
      and functional studies are needed to explore and clarify the potential mechanism.

PMID- 25983031
TI  - A prospective analysis of high-dose-rate endobronchial brachytherapy in the
      palliation of obstructive symptoms in lung cancer patients: A single-institution
      experience.
AB  - PURPOSE: Obstructive symptoms that affect quality of life (QOL) are commonly
      caused by endobronchial disease in many patients with locally advanced,
      inoperable lung cancer. High-dose-rate endobronchial brachytherapy (HDREBBT) has
      been used to palliate these symptoms, yet its role is not well defined in the
      literature. METHODS AND MATERIALS: Ninety-eight patients with locally advanced,
      inoperable lung cancer received HDREBBT. They were prospectively followed for
      survival, QOL, and toxicity endpoints. QOL measures were captured using the
      Quality of Life Questionnaire-Lung Cancer 30 and -Lung Cancer 13. RESULTS: At 1
      year follow-up, no significant toxicities were seen. Overall survival was 13.4%
      at 12 months (mean 192 days). Performance status, additional treatment after
      HDREBBT and treatment intent affected overall survival on univariate analysis (p
      < 0.05). Mean hemoptysis-free survival for all patients was 232.3 days, cough
      free survival was 140.3 days, and dyspnea-free survival was 173.5 days. There was
      no impact of any treatment- or patient-related factors of these outcomes on
      multivariate analysis, including additional treatment modalities and HDREBBT
      dose. CONCLUSIONS: HDREBBT is a safe and effective way to palliate endobronchial
      symptoms. Additional external-beam radiation therapy, chemotherapy, or
      chemoradiation after HDREBBT improves survival, but does not affect QOL measures.

PMID- 25983032
TI  - High CD133 Expression Is Associated with Worse Prognosis in Patients with
      Glioblastoma.
AB  - The CD133 antigen has been identified as a putative stem cell marker in gliomas.
      However, the prognostic significance of CD133 expression in glioblastoma patients
      remained controversial. A meta-analysis of published data was performed to
      comprehensively assess the prognostic role of CD133 expression in glioblastoma
      patients. Publications assessing the prognostic significance of CD133 expression
      in glioblastoma patients were identified in PubMed, Embase, and Web of Science up
      to November 2014. The pooled hazard ratio (HR) with 95% confidence interval (95%
      CI) was calculated using meta-analysis to evaluate the prognostic significance of
      CD133 expression in glioblastoma. Ten studies with a total of 715 glioblastoma
      patients were included into the meta-analysis. Overall, high CD133 expression was
      associated with poorer overall survival in patients with glioblastoma (HR = 1.96,
      95% CI 1.46-2.64, P < 0.001). In addition, high CD133 expression was also
      associated with poorer progression-free survival in patients with glioblastoma
      (HR = 2.03, 95% CI 1.43-2.88, P < 0.001). Meta-analyses of studies with high
      quality showed that high CD133 expression was associated with both poorer overall
      survival (HR = 2.39, 95% CI 1.77-3.23, P < 0.001) and poorer progression-free
      survival (HR = 2.17, 95% CI 1.60-2.94, P < 0.001) in patients with glioblastoma.
      Meta-analysis of studies with adjusted estimates further showed that high CD133
      expression was an independent prognostic factor of glioblastoma. High CD133
      expression is associated with worse prognosis in patients with glioblastoma. More
      prospective studies with well-design are needed to confirm this finding.

PMID- 25983035
TI  - Education and Risk of Dementia: Dose-Response Meta-Analysis of Prospective Cohort
      Studies.
AB  - Educational level has been regarded as one of the most widely accepted risk
      factors in the epidemiological studies for dementia, despite with discordant
      qualitative results. However, the dose-response relation between education and
      incident dementia was still unknown. To quantitatively evaluate the association
      between exposure level to high and low education and risk of dementia, we
      searched PubMed, EMBASE, and the Cochrane Library up to November 2014 and
      references of retrieved literatures. Specific prospective cohort studies, in
      which educational attainment was categorized into at least three levels, were
      included. Newcastle-Ottawa scale was used to assess the quality of included
      studies. Fifteen prospective cohort studies with 55655 for low education and
      eight prospective cohort studies with 20172 for high education were included. In
      the qualitative analysis, both low and high education showed a dose-response
      trend with risk of dementia and Alzheimer's disease (AD). In the quantitative
      analysis, the dementia risk was reduced by 7 % for per year increase in education
      (RR, 0.93; 95 % CI, 0.92-0.94; p for overall trend = 0.000; p for nonlinearity =
      0.0643). Nonetheless, we did not find statistically significant association
      between per year decrease in education and dementia (RR, 1.03; 95 % CI, 0.96
      1.10; p for overall trend = 0.283; p for nonlinearity = 0.0041) or AD (RR, 1.03;
      95 % CI, 0.97-1.10; p for overall trend = 0.357; p for nonlinearity = 0.0022).
      Both low and high education showed a trend of dose-response relation with risk of
      dementia and AD. The dementia risk was reduced by 7 % for per year increase in
      education.

PMID- 25983036
TI  - Region-specific alterations of AMPA receptor phosphorylation and signaling
      pathways in the pilocarpine model of epilepsy.
AB  - Disturbances in glutamatergic transmission and signaling pathways have been
      associated with temporal lobe epilepsy (TLE) in humans. However, the profile of
      these alterations within specific regions of the hippocampus and cerebral cortex
      has not yet been examined. The pilocarpine model in rodents reproduces the main
      features of TLE in humans. The present study aims to characterize specific
      alterations of the glutamatergic transmission and signaling pathways in the
      dorsal (DH) and ventral hippocampus (VH) and temporal cortex (Ctx) of male adult
      Wistar rats 60 days after pilocarpine treatment (chronic period). The western
      blotting analyzes show a decrease of AMPA glutamate receptor subunit (GluA1)
      Ser(845) phosphorylation; reduction of ERK1 and PKA activity; up-regulation of
      GFAP and down-regulation of the glutamate transporter EAAT2 expression in the DH.
      In contrast, in the VH it was observed a decrease of GluA1-Ser(831)
      phosphorylation and JNKp54 and PKC activity. In the Ctx, only ERK1
      phosphorylation/activity decreased. The level of GluA1-Ser(845) phosphorylation
      and PKA activity (DH) and the level of GluA1-Ser(831) phosphorylation and PKC
      activity (VH) appear to be correlated, respectively. These findings suggest a
      differential imbalance of the signaling pathways involved in the site-specific
      phosphorylation of AMPA receptor in the hippocampus. Furthermore, we suggest that
      dorsal hippocampus is probably more susceptible to the impairment of glutamate
      uptake and gliose, since only this area displayed a significant decrease of EAAT2
      and increment of GFAP. Taken together, our study suggests that specific
      neurochemical alterations take place in hippocampal sub regions. This approach
      may be valuable for understanding the onset of seizures and the alterations of
      neuronal excitability in specific regions and may help to establish therapeutic
      targets for treatment of this neuropathology. 

PMID- 25983033
TI  - HO-1 Signaling Activation by Pterostilbene Treatment Attenuates Mitochondrial
      Oxidative Damage Induced by Cerebral Ischemia Reperfusion Injury.
AB  - Ischemia reperfusion (IR) injury (IRI) is harmful to the cerebral system and
      causes mitochondrial oxidative stress. The antioxidant response element (ARE)
      mediated antioxidant pathway plays an important role in maintaining the redox
      status of the brain. Heme oxygenase-1 (HO-1), combined with potent AREs in the
      promoter of HO-1, is a highly effective therapeutic target for protection against
      cerebral IRI. Pterostilbene (PTE), a natural dimethylated analog of resveratrol
      from blueberries, is a strong natural antioxidant. PTE has been shown to be
      beneficial for some nervous system diseases and may regulate HO-1 signaling. This
      study was designed to investigate the protective effects of PTE on cerebral IRI
      and to elucidate potential mechanisms underlying those effects. Mouse brains and
      cultured HT22 neuron cells were subjected to IRI. Prior to this procedure, the
      brains or cells were exposed to PTE in the absence or presence of the HO-1
      inhibitor ZnPP or HO-1 small interfering RNA (siRNA). PTE conferred a cerebral
      protective effect, as shown by increased neurological scores, viable neurons and
      decreased brain edema as well as a decreased ion content and apoptotic ratio in
      vivo. PTE also increased the cell viability and decreased the lactate
      dehydrogenase (LDH) leakage and apoptotic ratio in vitro. ZnPP and HO-1 siRNA
      both blocked PTE-mediated cerebral protection by inhibiting HO-1 signaling and
      further inhibited two HO-1 signaling-related antioxidant molecules: NAD(P)H:
      quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs), which are
      induced by PTE. PTE also promoted a well-preserved mitochondrial membrane
      potential (MMP), mitochondria complex I activity, and mitochondria complex IV
      activity, increased the mitochondrial cytochrome c level, and decreased the
      cytosolic cytochrome c level. However, this PTE-elevated mitochondrial function
      was reversed by ZnPP or HO-1 siRNA treatment. In summary, our results demonstrate
      that PTE treatment attenuates cerebral IRI by reducing IR-induced mitochondrial
      oxidative damage through the activation of HO-1 signaling.

PMID- 25983034
TI  - N(epsilon)-Carboxymethyl Modification of Lysine Residues in Pathogenic Prion
      Isoforms.
AB  - The most prominent hallmark of prion diseases is prion protein conversion and the
      subsequent deposition of the altered prions, PrP(Sc), at the pathological sites
      of affected individuals, particularly in the brain. A previous study has
      demonstrated that the N-terminus of the pathogenic prion isoform (PrP(Sc)) is
      modified with advanced glycation end products (AGEs), most likely at one or more
      of the three Lys residues (positions 23, 24, and 27) in the N-terminus
      (23KKRPKP28). The current study investigated whether N(epsilon)
      (carboxymethyl)lysine (CML), a major AGE form specific to Lys residues produced
      by nonenzymatic glycation, is an AGE adduct of the N-terminus of PrP(Sc). We show
      that CML is linked to at least one Lys residue at the N-terminus of PrP(Sc) in
      263K prion-infected hamster brains and at least one of the eight Lys residues
      (positions 101, 104, 106, 110, 185, 194, 204, and 220) in the proteinase K (PK)
      resistant core region of PrP(Sc). The nonenzymatic glycation of the Lys
      residue(s) of PrP(Sc) with CML likely occurs in the widespread prion-deposit
      areas within infected brains, particularly in some of the numerous tyrosine
      hydroxylase-positive thalamic and hypothalamic nuclei. CML glycation does not
      occur in PrP(C) but is seen in the pathologic PrP(Sc) isoform. Furthermore, the
      modification of PrP(Sc) with CML may be closely involved in prion propagation and
      deposition in pathological brain areas.

PMID- 25983037
TI  - Characterization of diferuloylated pectic polysaccharides from quinoa
      (Chenopodium quinoa WILLD.).
AB  - In plants belonging to the order of Caryophyllales, pectic neutral side chains
      can be substituted with ferulic acid. The ability of ferulic acid to form intra-
      and/or intermolecular polysaccharide cross-links by dimerization was shown by the
      isolation and characterization of diferulic acid oligosaccharides from
      monocotyledonous plants. In this study, two diferulic acid oligosaccharides were
      isolated from the enzymatic hydrolyzate of seeds of the dicotyledonous
      pseudocereal quinoa by gel permeation chromatography and preparative HPLC and
      unambiguously identified by LC-MS(2) and 1D/2D NMR spectroscopy. The isolated
      oligosaccharides are comprised of 5-5- and 8-O-4-diferulic acid linked to the O2
      position of the nonreducing residue of two (1->5)-linked arabinobioses. To get
      insight into the structure and the degree of phenolic acid substitution of the
      diferuloylated polysaccharides, polymeric sugar composition, glycosidic linkages,
      and polysaccharide-bound monomeric phenolic acids and diferulic acids were
      analyzed. This study demonstrates that diferulic acids are involved into
      intramolecular and/or intermolecular cross-linking of arabinan chains and may
      have a major impact on cell wall architecture of quinoa and other dicotyledonous
      plants of the order of Caryophyllales. 

PMID- 25983038
TI  - Repair of transposable phage Mu DNA insertions begins only when the E. coli
      replisome collides with the transpososome.
AB  - We report a new cellular interaction between the infecting transposable phage Mu
      and the host Escherichia coli replication machinery during repair of Mu
      insertions, which involves filling-in of short target gaps on either side of the
      insertion, concomitant with degradation of extraneous long flanking DNA (FD)
      linked to Mu. Using the FD as a marker to follow repair, we find that after
      transposition into the chromosome, the unrepaired Mu is indefinitely stable until
      the replication fork arrives at the insertion site, whereupon the FD is rapidly
      degraded. When the fork runs into a Mu target gap, a double strand end (DSE) will
      result; we demonstrate fork-dependent DSEs proximal to Mu. These findings suggest
      that Pol III stalled at the transpososome is exploited for co-ordinated repair of
      both target gaps flanking Mu without replicating the intervening 37 kb of Mu,
      disassembling the stable transpososome in the process. This work is relevant to
      all transposable elements, including retroviral elements like HIV-1, which share
      with Mu the common problem of repair of their flanking target gaps. 

PMID- 25983039
TI  - Health-related quality of life in children with objectively diagnosed staple food
      allergy assessed with a disease-specific questionnaire.
AB  - AIM: Among Swedish children of 0-12 years old, we investigated various food
      allergy-related exposures associated with health-related quality of life using a
      food allergy-specific questionnaire among children allergic to the staple foods
      cow's milk, hen's egg and/or wheat, and contextualised worse food allergy
      associated health-related quality of life using a generic questionnaire versus
      controls. METHODS: In total, 85 children with objectively diagnosed allergy to
      the staple foods were included as cases, and 94 children matched for age and sex
      were included as controls. We administered a food allergy-specific parent
      completed questionnaire originally developed by EuroPrevall to cases only, and a
      generic health-related quality of life questionnaire (EuroQol Health
      Questionnaire, 5 Dimensions; EQ 5-D); to both cases and controls. RESULTS: Hen's
      egg was the most common offending staple food, affecting 76% of cases.
      Approximately 7% of cases were allergic to all three staple foods. Parent
      reported respiratory and cardiovascular symptoms were associated with worse
      health-related quality of life. Elements of disease severity [previous
      anaphylaxis (p < 0.001); epinephrine autoinjector prescription (p < 0.003)] were
      negatively associated with health-related quality of life. Cases had worse health
      related quality of life measured by the EQ-5D compared to controls (p < 0.01).
      CONCLUSION: The use of a disease-specific questionnaire revealed that disease
      severity in children with objectively diagnosed allergy to the staple foods cow's
      milk, hen's egg and/or wheat is associated with worse health-related quality of
      life. The use of a generic questionnaire confirmed that cases have worse health
      related quality of life than controls.

PMID- 25983040
TI  - Generation and tumor recognition properties of two human monoclonal antibodies
      specific to cell surface anionic phospholipids.
AB  - Phosphatidylserine (PS) and other anionic phospholipids, which become exposed on
      the surface of proliferating endothelial cells, tumor cells and certain
      leukocytes, have been used as targets for the development of clinical-stage
      biopharmaceuticals. One of these products (bavituximab) is currently being
      investigated in Phase 3 clinical trials. There are conflicting reports on the
      ability of bavituximab and other antibodies to recognize PS directly or through
      beta-2 glycoprotein 1, a serum protein that is not highly conserved across
      species. Here, we report on the generation and characterization of two fully
      human antibodies directed against phosphatidylserine. One of these antibodies
      (PS72) bound specifically to phosphatidylserine and to phosphatidic acid, but did
      not recognize other closely related phospholipids, while the other antibody
      (PS41) also bound to cardiolipin. Both PS72 and PS41 stained 8/9 experimental
      tumor models in vitro, but both antibodies failed to exhibit a preferential tumor
      accumulation in vivo, as revealed by quantitative biodistribution analysis. Our
      findings indicate that anionic phospholipids are exposed and accessible in most
      tumor types, but cast doubts about the possibility of efficiently targeting
      tumors in vivo with PS-specific reagents. 

PMID- 25983042
TI  - Neurological disease in human and canine leishmaniasis--clinical features and
      immunopathogenesis.
AB  - Leishmaniasis is a vectorborne disease caused by Leishmania protozoa, which is a
      major health problem and a neglected disease common in many regions of the world.
      Leishmania is an intracellular parasite transmitted by sand flies that causes
      clinical manifestations ranging from a severe and potentially fatal disease named
      visceral leishmaniasis to less severe but in many cases disfiguring diseases that
      mainly affect the skin or mucosal tissues, known as cutaneous leishmaniasis.
      Despite the detection of Leishmania parasites in the brain and cerebrospinal
      fluid of human patients and dogs, epidemiological data, as well as information
      about the mechanisms of central and peripheral nervous system alterations, are
      poorly described. This review is focused on the current knowledge about the
      neurological manifestations and immunopathogenic mechanisms in human patients and
      animals infected with Leishmania. 

PMID- 25983041
TI  - A phase II study of the HDAC inhibitor SB939 in patients with castration
      resistant prostate cancer: NCIC clinical trials group study IND195.
AB  - BACKGROUND: SB939 is a potent oral inhibitor of class 1, 2, and 4 histone
      deacetylases (HDACs). These three HDAC classes are highly expressed in castration
      resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We
      designed a phase II study of SB939 in men with metastatic CRPC. METHODS: Patients
      received SB939 60 mg on alternate days three times per week for 3 weeks on a 4
      week cycle. Primary endpoints were PSA response rate (RR) and progression-free
      survival (PFS). Secondary endpoints included objective response rate and
      duration; overall survival; circulating tumor cell (CTC) enumeration and safety.
      Exploratory correlative studies of the TMPRSS2-ERG fusion and PTEN biomarkers
      were also performed. RESULTS: Thirty-two patients were enrolled of whom 88 % had
      received no prior chemotherapy. The median number of SB939 cycles administered
      was three (range 1-8). Adverse events were generally grade 1-2, with five pts
      experiencing one or more grade three event. One patient died due to myocardial
      infarction. A confirmed PSA response was noted in two pts (6 %), lasting 3.0 and
      21.6 months. In patients with measurable disease there were no objective
      responses. Six patients had stable disease lasting 1.7 to 8.0 months. CTC
      response (from >=5 at baseline to <5 at 6 or 12 weeks) occurred in 9/14 evaluable
      patients (64 %). CONCLUSION: Although SB939 was tolerable at the dose/schedule
      given, and showed declines in CTC in the majority of evaluable patients, it did
      not show sufficient activity based on PSA RR to warrant further study as a single
      agent in unselected patients with CRPC.

PMID- 25983044
TI  - Ecological network analysis for carbon metabolism of eco-industrial parks: a case
      study of a typical eco-industrial park in Beijing.
AB  - Energy production and industrial processes are crucial economic sectors
      accounting for about 62% of greenhouse gas (GHG) emissions globally in 2012. Eco
      industrial parks are practical attempts to mitigate GHG emissions through
      cooperation among businesses and the local community in order to reduce waste and
      pollution, efficiently share resources, and help with the pursuit of sustainable
      development. This work developed a framework based on ecological network analysis
      to trace carbon metabolic processes in eco-industrial parks and applied it to a
      typical eco-industrial park in Beijing. Our findings show that the entire
      metabolic system is dominated by supply of primary goods from the external
      environment and final demand. The more carbon flows through a sector, the more
      influence it would exert upon the whole system. External environment and energy
      providers are the most active and dominating part of the carbon metabolic system,
      which should be the first target to mitigate emissions by increasing
      efficiencies. The carbon metabolism of the eco-industrial park can be seen as an
      evolutionary system with high levels of efficiency, but this may come at the
      expense of larger levels of resilience. This work may provide a useful modeling
      framework for low-carbon design and management of industrial parks.

PMID- 25983045
TI  - The systems perspective at the crossroads between chemistry and biology.
AB  - During the last century a number of authors pointed to the inherently systemic
      and dynamic nature of the living, yet their message was largely ignored by the
      mainstream of the scientific community. Tibor Ganti was one of those early
      pioneers, proposing a theoretical framework to understand the living principles
      in terms of chemical transformation cycles and their coupling. The turn of the
      century then brought with it a novel 'systems' paradigm, which shined light on
      all that previous work and carried many implications for the way we conceive of
      chemical and biological complexity today. In this article tribute is paid to some
      of those seminal contributions, highlighting the importance of adopting a systems
      view in present chemistry, particularly if plausible mechanisms of chemical
      evolution toward the first living entities want to be unraveled. We examine and
      put in perspective recent discoveries in the emerging subfield of 'prebiotic
      systems chemistry', reaching the conclusion that the functional coupling of
      protocellular subsystems (i.e., protometabolism, protogenome and membrane
      compartment) is the most challenging target to make qualitative advances in the
      problem of the origins of life. For the long-awaited goal of assembling an
      autonomous protocell from its most basic molecular building blocks, we further
      suggest that a systems integrative strategy should be considered from the
      earliest synthetic steps, already at the level of monomer precursors, opening the
      way to biogenesis. 

PMID- 25983043
TI  - Impact of Pretransplantation (18)F-fluorodeoxy Glucose-Positron Emission
      Tomography Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation
      for Non-Hodgkin Lymphoma.
AB  - Assessment with (18)F-fluorodeoxy glucose (FDG)-positron emission tomography
      (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be
      prognostic for outcomes. Patients with chemotherapy-sensitive non-Hodgkin
      lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International
      Blood and Marrow Transplantation Registry between 2007 and 2012 were included.
      Pre-HCT PET status (positive versus negative) was determined by the reporting
      transplantation centers. We analyzed 336 patients; median age was 55 years and
      60% were males. Follicular lymphoma (n = 104) was more common than large cell (n
      = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n =
      78); two thirds of the cohort received reduced-intensity conditioning; one half
      had unrelated donor grafts. Patients underwent PET scanning a median of 1 month
      (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET
      negative. At 3 years, relapse/progression, progression-free survival (PFS), and
      overall survival (OS) in PET-positive versus PET-negative groups were 40% versus
      26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73,
      respectively. On multivariate analysis, a positive pretransplantation PET was
      associated with an increased risk of relapse/progression (risk ratio [RR], 1.86;
      P = .001) but was not associated with increased mortality (RR, 1.29, 95%
      confidence interval [CI], .96 to 1.7; P = .08), therapy failure (RR, 1.32; 95%
      CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18;
      P = .22). PET status conferred no influence on graft-versus-host disease. A
      positive PET scan before HCT is associated with increased relapse risk but should
      not be interpreted as a barrier to a successful allograft. PET status does not
      appear to predict survival after allogeneic HCT for NHL.

PMID- 25983046
TI  - Tipping the mutation-selection balance: Limited migration increases the frequency
      of deleterious mutants.
AB  - Typical mutation-selection models assume well-mixed populations, but dispersal
      and migration within many natural populations is spatially limited. Such
      limitations can lead to enhanced variation among locations as different types
      become clustered in different places. Such clustering weakens competition between
      unlike types relative to competition between like types; thus, the rate by which
      a fitter type displaces an inferior competitor can be affected by the spatial
      scale of movement. In this paper, we use a birth-death model to show that limited
      migration can affect asexual populations by creating competitive refugia. We use
      a moment closure approach to show that as population structure is introduced by
      limiting migration, the equilibrial frequency of deleterious mutants increases.
      We support and extend the model through stochastic simulation, and we use a
      spatially explicit cellular automaton approach to corroborate the results. We
      discuss the implications of these results for standing variation in structured
      populations and adaptive valley crossing in Wright's "shifting balance" process. 

PMID- 25983047
TI  - Use of a Microsoft Excel based add-in program to calculate plasma sinistrin
      clearance by a two-compartment model analysis in dogs.
AB  - Assessment of renal function by means of plasma clearance of a suitable marker
      has become standard procedure for estimation of glomerular filtration rate (GFR).
      Sinistrin, a polyfructan solely cleared by the kidney, is often used for this
      purpose. Pharmacokinetic modeling using adequate software is necessary to
      calculate disappearance rate and half-life of sinistrin. The purpose of this
      study was to describe the use of a Microsoft excel based add-in program to
      calculate plasma sinistrin clearance, as well as additional pharmacokinetic
      parameters such as transfer rates (k), half-life (t1/2) and volume of
      distribution (Vss) for sinistrin in dogs with varying degrees of renal function. 

PMID- 25983048
TI  - Analysis of the S1 gene of the avian infectious bronchitis virus (IBV) reveals
      changes in the IBV genetic groups circulating in southern Thailand.
AB  - The new variants of the avian infectious bronchitis virus (IBV) produce a range
      of symptoms and cause global economic losses to the poultry industry. We
      investigated the S1 glycoprotein of 24 recent IBV isolates from chickens and
      demonstrated that two predominant genetic groups were circulating in southern
      Thailand between 2008 and 2013. Seven IBV variants, isolated from 2008 to 2009,
      were clustered in the Thailand THA001 group I while 15 IBV variants, isolated
      from 2009 to 2013, were classified into the QX-like group II. Moreover, a single
      isolate from a broiler was categorized into the Massachusetts-type, and an
      isolate from a layer belonged to the 4/91 type virus. Interestingly, both the IBV
      groups I and II were isolated from native chickens (62.5%) and caused a range of
      symptoms. Our results indicate that the QX-like viruses were predominant after
      2009, replacing the THA001 type viruses. Furthermore, native chickens may
      contribute to the epidemiology of IB. 

PMID- 25983049
TI  - Arsenic (As) contamination: A major risk factor in Xinjiang Uyghur autonomous
      region of China.
AB  - Xinjiang province is one of the unhealthiest region in China due to natural as
      well as man-made activities. Here soil and water having high concentration of
      multi-metals especially arsenic content in the soil and water is a major threat
      to the peoples which suffers regularly from arsenic contamination therefore
      multiple diseases and illness is the common phenomenon. Therefore this area
      urgently needed a comprehensive assessment by governmental and nongovernmental
      organization to cope up with this problem and find a miracle solution which can
      remediate soil and water quality. There peoples suffers much for the above
      mentioned reason. 

PMID- 25983050
TI  - Perception of Genetic Testing for Deafness and Factors Associated with Interest
      in Genetic Testing Among Deaf People in a Selected Population in Sub-Saharan
      Africa.
AB  - Understanding the perceptions of genetic testing by members of the deaf community
      may help in planning deafness genetics research, especially so in the context of
      strong adherence to cultural values as found among native Africans. Among Yorubas
      in Nigeria, deafness is perceived to be caused by some offensive actions of the
      mother during pregnancy, spiritual attack, and childhood infections. We studied
      attitudes towards, and acceptance of genetic testing by the deaf community in
      Nigeria. Structured questionnaires were administered to individuals sampled from
      the Vocational Training Centre for the Deaf, the religious Community, and
      government schools, among others. The main survey items elicited information
      about the community in which the deaf people participate, their awareness of
      genetic testing, whether or not they view genetic testing as acceptable, and
      their understanding of the purpose of genetic testing. There were 150 deaf
      participants (61.3 % males, 38.7 % females) with mean age of 26.7 years +/-9.8. A
      majority of survey respondents indicated they relate only with other members of
      the deaf community (78 %) and reported believing genetic testing does more good
      than harm (79.3 %); 57 % expressed interest in genetic testing. Interest in
      genetic testing for deafness or in genetic testing in pregnancy was not related
      to whether respondents relate primarily to the deaf or to the hearing community.
      However, a significantly higher number of male respondents and respondents with
      low education reported interest in genetic testing.

PMID- 25983051
TI  - Experiences of Women Who Underwent Predictive BRCA 1/2 Mutation Testing Before
      the Age of 30.
AB  - This qualitative interview study focuses on the experiences of a sample of
      British female BRCA 1/2 carriers who had predictive testing before the age of 30,
      which is the minimum age for breast screening in the UK. Following appropriate
      informed consent procedures participants were recruited through the Cancer
      Genetics Service for Wales. Semi-structured interviews were conducted face-to
      face with seven participants, transcribed in full and analyzed using thematic
      analysis. The motives for testing and perceived advantages described by
      participants were similar to those identified in previous studies with older
      participants, such as increased awareness and knowledge and feeling more in
      control. However some of the perceived disadvantages were specific to younger
      women, including feeling pressured to make important life decisions earlier than
      they would have liked, such as about family planning and risk reducing surgery.
      Participants also reported feeling abandoned or forgotten because of lack of
      ongoing clinical contact, or feeling "stuck waiting" for screening to begin.
      However, none felt that these disadvantages were a reason to regret having
      testing. Findings in this small study suggest that having BRCA 1/2 predictive
      testing can have positive outcomes for young women even though they may be unable
      to access interventions such as breast screening. However it may be helpful to
      encourage young women during pre-test counseling to explore the decisions and
      choices they may face. These young women could benefit from ongoing support and
      follow up and increased interaction with healthcare professionals. 

PMID- 25983052
TI  - Parents' Perspectives on Variants of Uncertain Significance from Chromosome
      Microarray Analysis.
AB  - Chromosomal microarray analysis (CMA) for unexplained anomalies and developmental
      delay has improved diagnosis rates, but results classified as variants of
      uncertain significance (VUS) may challenge both clinicians and families. We
      explored the impact of such results on families, including parental knowledge,
      understanding and interpretation. Semi-structured telephone interviews were
      conducted with parents (N = 14) who received genetic counseling for a VUS in
      their child. Transcripts were analyzed through an iterative coding process.
      Participants demonstrated a range of recall and personal interpretation regarding
      whether test results provided a causal explanation for their children's health
      issues. Participants maintained contradictory interpretations, describing results
      as answers while maintaining that little clarification of their child's condition
      had been provided. Reported benefits included obtaining medical services and
      personal validation. Parents described adaptation/coping processes similar to
      those occurring after positive test results. Recall of terminology, including
      "VUS" and precise CMA abnormalities, was poor. However, most demonstrated
      conceptual understanding of scientific uncertainty. All participants expressed
      intentions to return for recommended genetics follow-up but had misconceptions
      about how this would occur. These results provide insight into the patient-and
      family experience when receiving uncertain genomic findings, emphasize the
      importance of exploring uncertainty during the communication process, and
      highlight areas for potential attention or improvement in the clinical encounter.

PMID- 25983053
TI  - Process and pattern in cichlid radiations - inferences for understanding
      unusually high rates of evolutionary diversification.
AB  - The cichlid fish radiations in the African Great Lakes differ from all other
      known cases of rapid speciation in vertebrates by their spectacular trophic
      diversity and richness of sympatric species, comparable to the most rapid
      angiosperm radiations. I review factors that may have facilitated these
      radiations and compare these with insights from recent work on plant radiations.
      Work to date suggests that it was a coincidence of ecological opportunity,
      intrinsic ecological versatility and genomic flexibility, rapidly evolving
      behavioral mate choice and large amounts of standing genetic variation that
      permitted these spectacular fish radiations. I propose that spatially orthogonal
      gradients in the fit of phenotypes to the environment facilitate speciation
      because they allow colonization of alternative fitness peaks during clinal
      speciation despite local disruptive selection. Such gradients are manifold in
      lakes because of the interaction of water depth as an omnipresent third spatial
      dimension with other fitness-relevant variables. I introduce a conceptual model
      of adaptive radiation that integrates these elements and discuss its
      applicability to, and predictions for, plant radiations. 

PMID- 25983055
TI  - Synthesis, FTIR, UV-Vis and Photoluminescence characterizations of
      triethanolamine passivated CdO nanostructures.
AB  - In this study, triethanolamine (TEOA) capped CdO nanostructures had been
      synthesized by wet chemical method annealed at 648K were reported. The
      structural, morphological and optical properties of the samples were studied by X
      ray diffraction (XRD), Field emission scanning electron microscopy (FESEM) with
      energy dispersive spectra (EDS) analysis, Fourier transform infrared (FTIR)
      spectroscopy, UV-Vis spectroscopy and Photoluminescence (PL) techniques. The XRD
      spectrum showed that all the samples were cubic in structure. The presence of
      functional groups and chemical bonding had been confirmed by FTIR. UV-Vis
      measurements showed decreased band gap energy for TEOA capped CdO, when compared
      with uncapped CdO. The PL spectra of the CdO systems showed the red emission. 

PMID- 25983054
TI  - A novel baseline hepatitis B virus sequencing-based strategy for predicting
      adefovir antiviral response.
AB  - Adefovir dipivoxil (ADV) is used as first-line monotherapy or rescue therapy in
      chronic hepatitis B (CHB) patients. In this study, we sought to identify
      nucleotide changes in the reverse transcriptase (RT) of hepatitis B virus (HBV)
      at baseline and explore their predictive value for ADV antiviral response. Ultra
      deep pyrosequencing (UDPS) was utilized to determine HBV genetic variability
      within the RT region at baseline and during a 48-week ADV therapy. According to
      the viral load at the end of ADV treatment, all patients were classified into
      responders (HBV DNA level reduction of ? 3 log 10 IU/mL) and suboptimal
      responders (HBV DNA level reduction of <3 log 10 IU/mL). Based on UDPS data at
      baseline, we identified 11 nucleotide substitutions whose combination frequency
      was significantly associated with the antiviral response among 36 CHB patients in
      the study group. However, the baseline distribution and frequency of rt181 and
      rt236 substitutions known to confer ADV resistance was a poor predictor for the
      antiviral response. Compared with baseline serum HBeAg, HBV-DNA and ALT levels,
      the baseline HBV sequence-based model showed higher predictive accuracy for ADV
      response. In an independent cohort of 31 validation patients with CHB, the
      sequence-based model provided greater predictive potency than the HBeAg/HBV
      DNA/ALT and the HBeAg/HBV-DNA/ALT/sequence combinations. Taken together, we
      confirm the presence of ADV resistance variants in treatment-naive patients and
      firstly unravel the predictive value of the baseline mutations in the HBV RT
      region for ADV antiviral response.

PMID- 25983056
TI  - Changes in spectrochemical and catalytic properties of biopolymer anchored Cu(II)
      and Ni(II) catalysts by electron beam irradiation.
AB  - Chitosan (a biopolymer) anchored Cu(II) and Ni(II) Schiff base complexes,
      [M(OIAC)Cl2] (M: Cu/Ni and OIAC: ([2-oxo-1H-indol-3-ylidene]amino)chitosan) were
      electron beam irradiated by different doses (100 Gy, 1 kGy and 10 kGy). The
      electron beam has shown potential impact on biopolymer's support, in detail chain
      linking and chain scissoring, as evidenced by viscosity studies, FT-IR and X-ray
      diffraction spectroscopic techniques. Due to these structural changes, thermal
      properties of the complexes were found to be changed. The surface of these
      heterogeneous complexes was also effectually altered by electron beam. As a
      consequence, pores and holes were created as probed by SEM technique. The
      catalytic activity of both non-irradiated and irradiated complexes was
      investigated in the aerobic oxidation of cyclohexane using hydrogen peroxide
      oxidant. The catalytic ability of the complexes was enhanced significantly after
      irradiation as the result of surface changes. The reusability of the complexes
      was also greatly affected because of the structural variations in polymeric
      support. In terms of both better catalytic activity along with the reusability, 1
      kGy is suggested as the best dose to attain adequate increase in catalytic
      activity and good reusability.

PMID- 25983057
TI  - SERS investigations on orientation of 2-bromo-3-methyl-1,4-dimethoxy-9,10
      anthraquinone on silver nanoparticles.
AB  - Silver nanoparticles (Ag NPs) were prepared by solution combustion method with
      urea as fuel. Silver nanoparticles were characterized by UV-visible spectroscopy,
      X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques.
      Surface-enhanced Raman scattering (SERS) of 2-bromo-3-methyl-1,4-dimethoxy-9,10
      anthraquinone (BMDMAQ) adsorbed on silver nanoparticles was investigated. The
      orientation of BMDMAQ on silver nanoparticles was inferred from nRs and SERS
      spectral features. Density functional theory (DFT) calculation was also performed
      to study the theoretical performance. The observed spectral features such as the
      high intensity of C-H out-of-plane bending mode and ring C-C stretching mode
      revealed that BMDMAQ adsorbed on silver surface through 'stand-on' orientation.
      Anthraquinone (AQ) derivatives have wide biomedical application which includes
      laxatives, antimalarials and antineoplastics used in the treatment of cancer.
      This present study would help to identify the interaction of drug molecules with
      DNA. 

PMID- 25983058
TI  - Molecular dynamics simulation and TDDFT study of the structures and UV-vis
      absorption spectra of MCT-beta-CD and its inclusion complexes.
AB  - In this research, the inclusion ratios and inclusion constants of MCT-beta
      CD/PERM and MCT-beta-CD/CYPERM inclusion complexes were measured by UV-vis and
      fluorescence spectroscopy. The inclusion ratios are both 1:1, and the inclusion
      constants are 60 and 342.5 for MCT-beta-CD/PERM and MCT-beta-CD/CYPERM,
      respectively. The stabilities of inclusion complexes were investigated by MD
      simulation. MD shows that VDW energy plays a vital role in the stability of
      inclusion complex, and the destruction of inclusion complex is due to the
      increasing temperature. The UV-vis absorption spectra of MCT-beta-CD and its
      inclusion complexes were studied by time-dependent density functional theory
      (TDDFT) method employing BLYP-D3, B3LYP-D3 and M06-2X-D3 functionals. BLYP-D3
      well reproduces the UV-vis absorption spectrum and reveals that the absorption
      bands of MCT-beta-CD mainly arise from n->pi(*) and n->sigma(*) transition, and
      those of inclusion complexes mainly arise from intramolecular charge transfer
      (ICT). ICT results in the shift of main absorption bands of MCT-beta-CD. 

PMID- 25983059
TI  - Enhanced photo-catalytic activity of Sr and Ag co-doped TiO2 nanoparticles for
      the degradation of Direct Green-6 and Reactive Blue-160 under UV & visible light.
AB  - This work is focused on sol-gel synthesis of silver and strontium co-doped TiO2
      nanoparticles and their utilization as photo-catalysts in degradation of two
      textile dyes. Effect of pH, intensity of light, amount of photo-catalyst,
      concentration of dye, sensitizers, etc., were studied to optimize conditions for
      obtaining enhanced photo-catalytic activity of synthesized nanoparticles. XRD,
      BET, HR-TEM, EDAX and UV-Vis (diffused reflectance mode) techniques were used to
      characterize the nanoparticles. Interestingly, band gap of Sr and Ag co-doped
      TiO2 nanoparticles showed considerable narrowing (2.6 eV) when compared to Ag
      doped TiO2 (2.7 eV) and undoped TiO2 (3.17 eV) nanoparticles. Incorporation of Ag
      and Sr in the lattice of TiO2 could bring isolated energy levels near conduction
      and valence bands thus narrowing band gap. The XRD analysis shows that both Ag
      and Sr nanoparticles are finely dispersed on the surface of titania framework,
      without disturbing its crystalline structure. TEM images indicate that
      representative grain sizes of Ag-doped TiO2 & Sr and Ag co-doped TiO2
      nanoparticles are in the range of 8-20 nm and 11-25 nm, respectively. Effective
      degradation of Direct Green-6 (DG-6) and Reactive Blue-160 (RB-160) under UV and
      visible light has been achieved using the photo-catalysts. Sr and Ag co-doped
      TiO2 photo-catalysts showed higher catalytic activity during degradation process
      in visible region when compared to Ag-doped and undoped TiO2 nanoparticles which
      could be attributed to the interactive effect caused by band gap narrowing and
      enhancement in charge separation. For confirming degradation of the dyes, total
      organic carbon (TOC) content was monitored periodically.

PMID- 25983060
TI  - Theoretical calculations of a compound formed by Fe(+3) and tris(catechol).
AB  - Phenolic compounds generally have special smell, easily soluble in water, organic
      solvents (alcohols, esters, chloroform, ethyl acetate), in aqueous solutions of
      bases, colorless or colorful, crystalline and amorphous materials. Phenols form
      colorful complexes when they form compounds with heavy metals. In this study, the
      structural properties of a compound formed by catechol and Fe(+3) are
      investigated theoretically. The electronic and thermodynamic properties of the
      complex were also investigated in gas phase and organic solvents at B3LYP/6
      31+G(d,p) and B3LYP/6-311++G(d,p) basis set. The formation of Fe-tris(catechol)
      complex compound is exothermic, and it is difficult to obtain the complex as the
      temperature increases. The observed and calculated FT-IR and geometric parameters
      spectra are in good agreement with empirical. 

PMID- 25983061
TI  - Detection of glutathione within single erythrocyte of different ages and
      pathological state using microfluidic chips coupled with laser induced
      fluorescence.
AB  - As a major factor participating in the organism antioxidation and detoxification
      process, GSH is of vital importance to human beings. Detecting GSH content in
      single cells is significant to diagnosis and prevention of many diseases. In this
      work, the amount of GSH within single erythrocytes was detected and analyzed via
      statistical analysis. All erythrocytes tested were collected from people in
      different ages and people of different pathological states. The correlation
      between GSH level, age and pathological state were investigated. Results showed
      that the GSH level in erythrocytes decreased with the ages of patients increased.
      There was little difference between the GSH level in erythrocytes from people who
      had chronic diseases (hyperglycemia, hyperlipidemia and hypertension) and from
      healthy people. However, the GSH level in erythrocytes from people who had
      inflammation (myocarditis, nephritis and gastritis) was generally higher than
      that from the healthy people. This study provides basic data for researches of
      cell senescence and cytopathic effect and is helpful to diagnosis and prevention
      of diseases. In addition, it also provides a simple and effective method for
      rapid GSH detection within single cell. 

PMID- 25983062
TI  - P2X7 receptor is critical in alpha-synuclein--mediated microglial NADPH oxidase
      activation.
AB  - Activated microglia are commonly observed in individuals with neurodegenerative
      disorders, including Parkinson's disease (PD) and are believed to contribute to
      neuronal death. This process occurs at least due partially to nicotinamide
      adenine dinucleotide phosphate oxidase (PHOX) activation, which leads to the
      production of superoxide and oxidative stress. alpha-Synuclein (alpha-Syn), a key
      protein implicated in PD pathogenesis, can activate microglia, contributing to
      death of dopaminergic neurons. Here, microglial cells (BV2) and primary cultured
      microglia were used to study the role that the purinergic receptor P2X7 plays in
      recognizing alpha-Syn and promoting PHOX activation. We demonstrate that both
      wild type and A53T mutant alpha-Syn readily activate PHOX, with the A53T form
      producing more rapid and sustained effects,that is, oxidative stress and cellular
      injuries. Furthermore, this process involves the activation of phosphoinositide 3
      kinase (PI3K)/AKT (protein kinase B) pathway. Thus, it is concluded that
      stimulation of the microglial P2X7 receptor by extracellular alpha-Syn, with
      PI3K/AKT activation and increased oxidative stress, could be an important
      mechanism and a potential therapeutic target for PD. 

PMID- 25983064
TI  - On the Extreme Oxidation States of Iridium.
AB  - It has recently been suggested that the oxidation states of Ir run from the
      putative -III in the synthesized solid Na3 [Ir(CO)3 ] to the well-documented +IX
      in the species IrO4 (+) . Furthermore, [Ir(CO)3 ](3-) was identified as an 18
      electron species. A closer DFT study now finds support for this picture: The
      orbitals spanned by the 6s,6p,5d orbitals of the iridium are all occupied.
      Although some have considerable ligand character, the deviations from 18 e leave
      the orbital symmetries unchanged. The isoelectronic systems from Os(-IV) to Au(
      I) behave similarly, suggesting further possible species. To paraphrase Richard
      P. Feynmann "there is plenty of room at the bottom". 

PMID- 25983063
TI  - Chlorpyrifos and malathion have opposite effects on behaviors and brain size that
      are not correlated to changes in AChE activity.
AB  - Organophosphates, a type of neurotoxicant pesticide, are used globally for the
      treatment of pests on croplands and are therefore found in a large number of
      conventional foods. These pesticides are harmful and potentially deadly if
      ingested or inhaled in large quantities by causing a significant reduction in
      acetylcholinesterase (AChE) activity in the central and peripheral nervous
      system. However, much less is known about the effects of exposure to small
      quantities of the pesticides on neural systems and behavior during development.
      In the current study we used zebrafish larvae in order to determine the effects
      of two of the most widely used organophosphates, chlorpyrifos and malathion, on
      zebrafish behavior and AChE activity. Embryos and larvae were exposed to the
      organophosphates during different time points in development and then tested at 5
      days post-fertilization for behavioral, neurodevelopmental and AChE
      abnormalities. The results of the study indicate that chlorpyrifos and malathion
      cause opposing behaviors in the larvae such as swim speed (hypoactivity vs.
      hyperactivity) and rest. Additionally, the pesticides affect only certain
      behaviors, such as thigmotaxis, during specific time points in development that
      are unrelated to changes in AChE activity. Larvae treated with malathion but not
      chlorpyrifos also had significantly smaller forebrain and hindbrain regions
      compared to controls by 5 days post-fertilization. We conclude that exposure to
      very low concentrations of organophosphate pesticides during development cause
      abnormalities in behavior and brain size. 

PMID- 25983065
TI  - Multivariable robust adaptive sliding mode control of an industrial boiler
      turbine in the presence of modeling imprecisions and external disturbances: A
      comparison with type-I servo controller.
AB  - To guarantee the safety and efficient performance of the power plant, a robust
      controller for the boiler-turbine unit is needed. In this paper, a robust
      adaptive sliding mode controller (RASMC) is proposed to control a nonlinear multi
      input multi-output (MIMO) model of industrial boiler-turbine unit, in the
      presence of unknown bounded uncertainties and external disturbances. To overcome
      the coupled nonlinearities and investigate the zero dynamics, input-output
      linearization is performed, and then the new decoupled inputs are derived. To
      tackle the uncertainties and external disturbances, appropriate adaption laws are
      introduced. For constructing the RASMC, suitable sliding surface is considered.
      To guarantee the sliding motion occurrence, appropriate control laws are
      constructed. Then the robustness and stability of the proposed RASMC is proved
      via Lyapunov stability theory. To compare the performance of the purposed RASMC
      with traditional control schemes, a type-I servo controller is designed. To
      evaluate the performance of the proposed control schemes, simulation studies on
      nonlinear MIMO dynamic system in the presence of high frequency bounded
      uncertainties and external disturbances are conducted and compared. Comparison of
      the results reveals the superiority of proposed RASMC over the traditional
      control schemes. RAMSC acts efficiently in disturbance rejection and keeping the
      system behavior in desirable tracking objectives, without the existence of
      unstable quasi-periodic solutions. 

PMID- 25983066
TI  - Evaluation of delamination in drilling of bone.
AB  - In this paper, delamination of bone associated with drilling is investigated
      using design of experiments. Experiments have been planned based on L25 design of
      the orthogonal arrays with different conditions of drill bit, spindle speed and
      feed rate. Regression analysis is used to develop a mathematical model of
      delamination as a function of bone drilling process parameters. Analysis of
      variance (ANOVA) is carried out to find the significance of the developed model
      along with the percentage contribution of each factor on delamination. Optimum
      setting of bone drilling parameters for minimum delamination is determined using
      Taguchi optimization methodology. Finally, the results obtained are validated by
      conducting confirmation experiments. 

PMID- 25983067
TI  - Varying behavior of different window sizes on the classification of static and
      dynamic physical activities from a single accelerometer.
AB  - Accuracy of systems able to recognize in real time daily living activities
      heavily depends on the processing step for signal segmentation. So far, windowing
      approaches are used to segment data and the window size is usually chosen based
      on previous studies. However, literature is vague on the investigation of its
      effect on the obtained activity recognition accuracy, if both short and long
      duration activities are considered. In this work, we present the impact of window
      size on the recognition of daily living activities, where transitions between
      different activities are also taken into account. The study was conducted on nine
      participants who wore a tri-axial accelerometer on their waist and performed some
      short (sitting, standing, and transitions between activities) and long (walking,
      stair descending and stair ascending) duration activities. Five different
      classifiers were tested, and among the different window sizes, it was found that
      1.5 s window size represents the best trade-off in recognition among activities,
      with an obtained accuracy well above 90%. Differences in recognition accuracy for
      each activity highlight the utility of developing adaptive segmentation criteria,
      based on the duration of the activities. 

PMID- 25983068
TI  - Sensitivities of biomechanical assessment methods for fracture healing of long
      bones.
AB  - There is a controversy as to whether the biomechanical methods are feasible to
      assess fracture healing of long bones. This paper investigated the sensitivities
      of two biomechanical methods, torsion and bending, for assessing fracture healing
      of long bones; both a simplified beam model and finite element model of an
      artificial femur were employed. The results demonstrated that, in the initial
      healing stage, the whole-bone stiffness of the fractured bone is extremely
      sensitive to the variation of the callus stiffness at the fracture site; when the
      shear (or Young's) modulus of the callus reaches 15% that of the intact bone, the
      whole-bone stiffness rises up to 90% that of the intact bone. After that, the
      whole-bone torsional (or bending) stiffness increases slowly; it becomes less
      sensitive to the variation of the callus stiffness. These results imply that the
      whole-bone stiffness is of limited reliability to assess the healing quality
      particular at late stages of the healing process. The simplified model in this
      paper provided a theoretical framework to explain why the whole-bone stiffness is
      insensitive to the healing process of fractured long bones in the late stage of
      healing. The conclusions obtained from the simplified model were verified with
      the finite element simulations of the artificial femur. 

PMID- 25983069
TI  - The developmental trajectory of disruptive behavior in Down syndrome, fragile X
      syndrome, Prader-Willi syndrome and Williams syndrome.
AB  - The aim of this study was to investigate the developmental trajectories of verbal
      aggression, physical aggression, and temper tantrums in four genetic syndrome
      groups. Participants were part of the Australian Child to Adult Development Study
      (ACAD), which collected information from a cohort of individuals with an
      intellectual disability at five time points over 18 years. Data were examined
      from a total of 248 people with one of the four following syndromes: Down
      syndrome, Fragile X syndrome, Prader-Willi syndrome, or Williams syndrome.
      Changes in behaviors were measured using validated items from the Developmental
      Behavior Checklist (DBC). The results indicate that, while verbal aggression
      shows no evidence of diminishing with age, physical aggression, and temper
      tantrums decline with age before 19 years for people with Down syndrome, Fragile
      X syndrome, and William syndrome; and after 19 years for people with Prader-Willi
      syndrome. These findings offer a somewhat more optimistic outlook for people with
      an intellectual disability than has previously been suggested. Research is needed
      to investigate the mechanisms predisposing people with PWS to persistence of
      temper tantrums and physical aggression into adulthood.

PMID- 25983070
TI  - Optical differentiation between malignant and benign lymphadenopathy by EBUS
      using grey scale texture analysis.

PMID- 25983072
TI  - MY APPROACH to detecting and managing peripheral artery disease.

PMID- 25983073
TI  - MY APPROACH to the patient with peripartum cardiomyopathy.

PMID- 25983071
TI  - Behavioral influences on cardiac arrhythmias.
AB  - Stress can trigger both ventricular and atrial arrhythmias, as evidenced by
      epidemiological, clinical, and laboratory studies, through its impact on
      autonomic activity. Chronic stress also increases vulnerability to arrhythmias.
      Novel therapies aimed at decreasing the psychological and physiological response
      to stress may decrease arrhythmia frequency and improve quality of life. 

PMID- 25983074
TI  - Sudden cardiac death: We are not there yet.

PMID- 25983075
TI  - MY APPROACH to the patient with right ventricular failure.

PMID- 25983076
TI  - Heritability estimates for somatic traits determined perinatally with the twin
      method.
AB  - The aim of this study was to establish estimates for heritability of somatic
      traits determined perinatally with the twin method. The studied material,
      including 1263 twin pairs live-born at various stages of prenatal life, i.e.
      between the 22nd and 41st week of gestation, was collected at the Department of
      Perinatology and Gynecology, Poznan University of Medical Sciences, between 2002
      and 2009. The zygosity of 821 pairs of same-sex twins was determined at the
      Laboratory of Molecular Genetics in Poznan using analysis of single and multiple
      nucleotide polymorphisms. The proportion of phenotypic variance explained by
      genetic variability was determined using heritability indices based on intrapair
      variances and correlations. Analysis of these indices revealed that genetic
      variability predominated over environmental variability in determining the
      phenotypic variance of all studied traits. Heritability was the highest for body
      weight and shoulder width. The high values of heritability coefficients
      documented in our study were to a certain extent associated with an inconsistency
      of the assumption on the additive effect of genetic and environmental effects.
      While analyzing the phenotypic variance of a trait, the role of genotype
      environment interactions and covariance cannot be ignored, as these are their
      effects which increase the genetic variance and related coefficients of
      heritability. Therefore, it can be concluded that the genotypic component of the
      phenotypic variance of the trait is enhanced by the effects of various
      environmental factors. 

PMID- 25983077
TI  - The male-taller norm: Lack of evidence from a developing country.
AB  - In general, women prefer men taller than themselves; this is referred to as the
      male-taller norm. However, since women are shorter than men on average, it is
      difficult to determine whether the fact that married women are on average shorter
      than their husbands results from the norm or is a simple artifact generated by
      the shorter stature of women. This study addresses the question by comparing the
      rate of adherence to the male-taller norm between actual mating and hypothetical
      random mating. A total of 7954 actually married couples are drawn from the last
      follow-up of the Indonesian Family Life Survey, a nationally representative
      survey. Their heights were measured by trained nurses. About 10,000 individuals
      are randomly sampled from the actual couples and randomly matched. An alternative
      random mating of about 100,000 couples is also performed, taking into account an
      age difference of 5 years within a couple. The rate of adherence to the male
      taller norm is 93.4% for actual couples and 88.8% for random couples. The
      difference between the two figures is statistically significant, but it is
      emphasized that it is very small. The alternative random mating produces a rate
      of 91.4%. The male-taller norm exists in Indonesia, but only in a statistical
      sense. The small difference suggests that the norm is mostly explained by the
      fact that women are shorter than men on average. 

PMID- 25983079
TI  - A modified Glenn shunt reduces right ventricular stroke work during left
      ventricular assist device therapy.
AB  - OBJECTIVES: Right ventricular (RV) failure is a major cause of morbidity and
      mortality after left ventricular assist device (LVAD) placement and remains hard
      to predict. We hypothesized that partial surgical exclusion of the RV with a
      modified Glenn shunt during LVAD treatment would reduce RV stroke work. METHODS:
      An LVAD was implanted in eight pigs and a modified Glenn shunt was constructed. A
      conductance pressure-volume catheter was placed in the right ventricle through
      the apex. Haemodynamic data and pressure-volume loops were obtained at the
      following time periods: (i) baseline, (ii) open shunt, (iii) LVAD with closed
      shunt and (iii) LVAD and open shunt. RESULTS: During LVAD therapy, the right
      atrial (RA) pressure increased from 9 mmHg (9-9) to 15 mmHg (12-15), P = 0.01. RV
      stroke volume increased from 30 ml (29-40) to 51 ml (42-53), P < 0.01. Also, RV
      stroke work increased to 708 mmHg ml (654-1193) from 535 mmHg ml (424-717), P =
      0.04, compared with baseline. During LVAD therapy in combination with a Glenn
      shunt, the RA pressure decreased from 15 mmHg (12-15) to 10 mmHg (7-11) when
      compared with LVAD therapy only, P = 0.01. A decrease in RV stroke work from 708
      mmHg ml (654-1193) to 465 mmHg ml (366-711), P = 0.04, was seen when the LVAD was
      combined with a shunt, not significantly different from the baseline value (535
      mmHg ml). The developed pressure in the right ventricle decreased from 29 mmHg
      (26-32) to 21 mmHg (20-24), P < 0.01. The pressure-volume loops of the RV show a
      significant reduction of RV stroke work during the use of the shunt with LVAD
      treatment. CONCLUSIONS: A modified Glenn shunt reduced RV volumes, RV stroke work
      and RA pressure during LVAD therapy in an experimental model of heart failure in
      pigs.

PMID- 25983078
TI  - Chronic hypoxia in pregnancy affected vascular tone of renal interlobar arteries
      in the offspring.
AB  - Hypoxia during pregnancy could affect development of fetuses as well as
      cardiovascular systems in the offspring. This study was the first to demonstrate
      the influence and related mechanisms of prenatal hypoxia (PH) on renal interlobar
      arteries (RIA) in the 5-month-old male rat offspring. Following chronic hypoxia
      during pregnancy, phenylephrine induced significantly higher pressor responses
      and greater vasoconstrictions in the offspring. Nitric oxide mediated vessel
      relaxation was altered in the RIA. Phenylephrine-stimulated free intracellular
      calcium was significantly higher in the RIA of the PH group. The activity and
      expression of L-type calcium channel (Cav1.2), not T-type calcium channel
      (Cav3.2), was up-regulated. The whole-cell currents of calcium channels and the
      currents of Cav1.2 were increased compared with the control. In addition, the
      whole-cell K(+) currents were decreased in the offspring exposed to prenatal
      hypoxia. Activity of large-conductance Ca(2+)-activated K(+) channels and the
      expression of MaxiKalpha was decreased in the PH group. The results provide new
      information regarding the influence of prenatal hypoxia on the development of the
      renal vascular system, and possible underlying cellular and ion channel
      mechanisms involved. 

PMID- 25983080
TI  - Development of a prediction model and risk score for procedure-related
      complications in patients undergoing percutaneous computed tomography-guided lung
      biopsy.
AB  - OBJECTIVES: To propose a risk score predicting the potential occurrence of
      procedure-related complications in patients undergoing computed tomography (CT)
      guided lung biopsy. METHODS: Institution review board approval was obtained. A
      total of 342 CT-guided lung biopsies were retrospectively evaluated taking into
      account procedure-related complications and associated risk factors, including
      patient gender and age, previous radiation therapy (RT) and/or chemotherapy
      (CHT), lesion size, depth and location, incomplete pulmonary fissures, associated
      diffuse lung diseases, previous pneumothorax (PNX), lung volumes, punctured
      fissures, thoracic access, needle size and operator experience. Complications
      were assessed on chest X-ray and/or CT scans. Stepwise logistic regression was
      used to identify risk factors, to evaluate their correlation with procedure
      related complications and to calculate models of risk (MoRs). RESULTS: PNX
      requiring chest tube placement occurred in 39 patients (11.4%), high-grade
      pulmonary parenchymal haemorrhage occurred in 62 patients (18.1%) and haemothorax
      occurred in 12 patients (3.5%). Risk factors increasing the incidence of
      complications were lesion size (P = 0.01), lesion depth (P = 0.01) and incomplete
      pulmonary fissures (P = 0.01); previous chemo-radiation therapy was correlated to
      a lower incidence of complications (P = 0.01). MoR for PNX was as follows: risk
      base line = 60%; age = +0.15%/year; punctured fissures = +20%; incomplete
      fissures = +9%; previous CHT/RT = -10%. MoR for parenchymal haemorrhage was as
      follows: risk base line = 20%, lesion depth = +0.8%/mm; age = +0.25%/year;
      incomplete fissures = +15%. MoR for haemothorax was as follows: risk base line =
      1%; previous PNX = +20%; incomplete fissures = 7%; both previous PNX and
      incomplete fissures = +67%. CONCLUSION: This study provides MoRs to predict the
      risk of complications in patients undergoing CT-guided percutaneous lung
      biopsies.

PMID- 25983081
TI  - An unexpected case of a hydatid cyst on the mitral valve mimicking infective
      endocarditis.

PMID- 25983082
TI  - The ubiquitin-like modifier FAT10 in antigen processing and antimicrobial
      defense.
AB  - The ubiquitin-like modifier (ULM) HLA-F adjacent transcript 10 (FAT10) is encoded
      in the MHC locus, is up-regulated during dendritic cell maturation, is highly
      expressed in lymphoid tissues, and strongly induced by interferon (IFN)-gamma and
      tumor necrosis factor (TNF)-alpha. FAT10 is the only ULM known to date which
      directly targets its hundreds of substrates for degradation by the proteasome.
      This implies a role for FAT10 in antigen presentation. Indeed, fusion of FAT10 to
      viral proteins enhanced their presentation along the proteasome dependent MHC
      class I presentation pathway. In this review we discuss the FAT10 conjugation
      system as an alternative and distinct pathway for MHC class I and II antigen
      processing. Furthermore, we review the recent finding that FAT10 plays a role in
      antimicrobial defense against intracellular pathogens. 

PMID- 25983083
TI  - Identifying and Applying for Professional Development Funding.
AB  - Participation in ongoing professional development can be critical for maintaining
      up-to-date knowledge in your field, as well as preparing for promotions and job
      changes. Career development activities may include formal classroom education,
      web-based courses, on-the-job training, workshops and seminars, professional
      conferences, and self-study programs. Developing a career development plan,
      cultivating a team to support your goals, and actively pursuing continuing
      education and skill-building opportunities are important across all career
      stages. However, the financial cost of these opportunities can often place them
      beyond reach. In this commentary, we summarize several potential sources for
      career development funding as well as best practices for completing the
      application process. 

PMID- 25983084
TI  - An Iterative Process for Developing and Evaluating a Computer-Based Prostate
      Cancer Decision Aid for African American Men.
AB  - BACKGROUND: The disproportionate burden of prostate cancer (PrCA) among African
      American (AA) men amplifies the need for informed decisions about PrCA screening.
      To create a computer-based decision aid (CBDA) for increasing prostate knowledge,
      decision self-efficacy, and intention to make an informed decision, the study
      implemented an iterative approach to develop a culturally appropriate CBDA.
      METHOD: A short CBDA prototype containing PrCA information and interactive
      activities was developed. A sample of 21 AA men aged 37 to 66 years in South
      Carolina participated in one of seven 90-minute focus groups and completed a 36
      item survey. Updates were made to the CBDA based on participant feedback. The
      CBDA and heuristic evaluation surveys were then distributed to six expert
      reviewers. Ten men were also randomly selected from our sample population to
      participate in interviews regarding usability of the CBDA. RESULTS: Participants
      and expert reviewers expressed consensus on many features of the CBDA, but some
      suggested changes to the format and graphics in order to enhance the CBDA's
      effectiveness. Development and evaluation processes and implications are
      discussed. CONCLUSIONS: Using CBDAs for informed decision making may be
      appropriate for AA men. It is important to engage the community and experts in an
      iterative development process to ensure that a CBDA is relevant for priority
      populations.

PMID- 25983085
TI  - Against Colorectal Cancer in Our Neighborhoods, a Community-Based Colorectal
      Cancer Screening Program Targeting Low-Income Hispanics: Program Development and
      Costs.
AB  - BACKGROUND: Colorectal cancer is the second leading cause of cancer-related death
      in the United States. Despite universal screening recommendations, screening
      rates in the United States remain suboptimal, especially among the poor, the
      uninsured, recent immigrants, and Hispanics. This article describes the
      development of a large community-based colorectal cancer screening program
      designed to address these disparities. METHOD: The Against Colorectal Cancer in
      our Neighborhoods program is a bilingual, evidence-based, theory-guided,
      multicomponent community screening intervention, targeting the uninsured and
      developed using a systematic planning process. It combines community health
      worker-led outreach, bilingual and culturally tailored community education, and
      no-cost screening with provision of the fecal immunochemical test or colonoscopy
      and navigation services. A detailed process and outcome evaluation is planned.
      Program development cost calculated prospectively (in 2011 dollars) using a
      societal perspective and micro-costing methods was $243,278, of which $180,344
      was direct cost. DISCUSSION: The detailed description of the development
      processes and costs of this health promotion program targeting low-income
      Hispanics will inform health program decision makers about the resource
      requirements for planning and developing new programs to reduce disease burden in
      communities.

PMID- 25983086
TI  - Diffusion tensor imaging study on radiation-induced brain injury in
      nasopharyngeal carcinoma during and after radiotherapy.
AB  - AIMS AND BACKGROUND: The aim of this study was to monitor the mircostructure
      change of temporal lobe during the acute and subacute stage of radiation-induced
      brain injury using magnetic resonance diffusion tensor imaging (DTI) in
      nasopharyngeal carcinoma patients. METHODS AND STUDY DESIGN: Eighty patients
      diagnosed with nasopharyngeal carcinoma and treated with the first radiotherapy
      from July 2010 to May 2012 were enrolled. Routine brain magnetic resonance
      imaging (MRI) and DTI were conducted in all patients before and during
      radiotherapy (radiation dose was 20, 40, and 60 Gy, respectively). The MRI and
      DTI were also performed in the 1st, 2nd, and 3rd month after radiotherapy in 47
      cases of 80 patients. The apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) of DTI during different stages were dynamically observed and
      analyzed. RESULTS: The ADC values were increased and the FA values were decreased
      with the increase of radiation dose (20, 40, and 60 Gy) during the radiotherapy,
      but there was no significant difference in ADC value or FA value between before
      and during radiotherapy (p>0.05). Compared with before radiotherapy, the ADC
      values were significantly increased and the FA values were significantly
      decreased at the 1st month, 2nd month, and 3rd month after radiotherapy (all
      p<0.05). CONCLUSIONS: Diffusion tensor imaging reflects the microstructure change
      of radiation-induced brain injury in the acute and subacute stage, which provides
      an objective basis for early intervention of potential irreversible brain injury
      in the late delayed stage, and has important significance for improving the
      overall efficacy of radiotherapy.

PMID- 25983087
TI  - Identification of the interaction network of hub genes for melanoma treated with
      vemurafenib based on microarray data.
AB  - AIMS AND BACKGROUND: The objective of this study was to identify possible
      biomarkers and to explore the mechanisms of suppression of vemurafenib on
      melanoma progression. METHODS: GSE42872 affymetrix microarray data were
      downloaded from the Gene Expression Omnibus database for further analysis.
      Differentially expressed genes (DEGs) between vehicle-treated samples and
      vemurafenib-treated samples were identified. Gene ontology and pathway enrichment
      analysis of DEGs were performed, followed by protein-protein interaction (PPI)
      network construction. Furthermore, the functional modules of the PPI network were
      screened using BioNet analysis tool. Finally, Kyoto Encyclopedia of Genes and
      Genomes pathway enrichment analysis was performed for DEGs in the module.
      RESULTS: In total, 794 upregulated transcripts corresponding to 214 genes and 977
      downregulated transcripts corresponding to 325 genes were screened. The
      downregulated DEGs were significantly enriched in pathways such as cell cycle,
      DNA replication, and p53 signaling pathway. Upregulated DEGs were significantly
      enriched in phosphatidylinositol signaling system and inositol phosphate
      metabolism. Significantly enriched functions of downregulated DEGs were mitotic
      cell cycle, nuclear division, DNA metabolic process, cell cycle, and mitosis.
      Upregulated DEGs were mainly enriched in single multicellular organism process
      and multicellular organismal process. Moreover, cell division cycle 6, checkpoint
      kinase 1 (CHEK1), E2F transcription factor 1 (E2F1), epidermal growth factor
      receptor (EGFR), and phosphoinositide-3-kinase, regulatory subunit 1-alpha
      (PIK3R1) of the module were remarkably enriched in pathways such as cell cycle,
      apoptosis, focal adhesion, and DNA replication. CONCLUSIONS: Cell division cycle
      6, CHEK1, E2F1, EGFR, and PIK3R1 of the module and their relative pathways, cell
      cycle, and focal adhesion might play important roles of suppression of
      vemurafenib on melanoma progression.

PMID- 25983088
TI  - Breakthrough pain management in patients undergoing radiotherapy: a national
      survey on behalf of the Palliative and Supportive Care Study Group.
AB  - AIMS: To assess the contribution of radiation oncologists in Italy in current
      management of breakthrough pain (BtP). METHODS: In 2012, the Palliative and
      Supportive Care Study Group of the Italian Association of Radiation Oncology
      (AIRO) proposed a survey. All Italian radiation oncologists were individually
      invited to complete an online questionnaire regarding their management of BtP in
      patients undergoing radiotherapy treatment. RESULTS: A total of 303 Italian
      radiation oncologists (of 330 who had access to the Web site) completed the
      questionnaire over an 8-month period. Some important differences were shown in
      pain intensity assessment by validated measurement scales, as well as in setting
      and prescribing analgesic therapy to prevent procedural pain. These differences
      were also reviewed and discussed related to international guidelines and data
      available from the literature. CONCLUSIONS: Compared to other medical
      professionals, the involvement of radiation oncologists in cancer pain management
      remains marginal, at least in Italy. More than 70% of radiation oncologists
      directly optimized the analgesic therapy during the treatment course and more
      than 50% implemented specific treatment for BtP. However, the ability of the
      radiation oncologist to manage BtP could be improved. In order to increase the
      consciousness of systematic symptom measurement and to spread the knowledge of
      the best type of analgesic drugs to be used, training events promoted by national
      associations, such as AIRO, and a collaborative multidisciplinary approach of the
      management of cancer pain will be promoted.

PMID- 25983089
TI  - Enhanced protective immunity derived from dendritic cells with phagocytosis of
      CD40 ligand transgene-engineered apoptotic tumor cells via increased dendritic
      cell maturation.
AB  - AIMS AND BACKGROUND: Dendritic cells (DCs) play a pivotal role in regulating CD8+
      cytotoxic T-lymphocyte (CTL) responses. Currently, DC vaccines have been used in
      experimental animal models and clinical trials for evaluation of antitumor
      immunity. However, their efficacy is limited, warranting the improvement of DC
      based cancer vaccines. CD40 ligand (CD40L) stimulates DC activation and
      maturation via CD40-CD40L interaction. We demonstrated that DCs that had
      phagocytized apoptotic tumor cells induced antitumor immunity. METHODS: We
      generated CD40L-expressing (EG7-CD40L) and the control (EG7-Null) EG7 tumor cells
      by transfection of EG7 tumor cells with CD40L-expressing adenoviral vector
      AdVCD40L and the control vector AdV(pLpA), respectively. We also generated DC
      vaccines (DC-EG7/CD40L and the control DC-EG7/Null) using DCs with phagocytosis
      of irradiated EG7-CD40L and EG7-Null tumor cells, and assessed their phenotype
      and immunogenicity by flow cytometry and animal studies in C57BL/6 mice. RESULTS:
      We demonstrate that an irradiation of 9000-rad induced Annexin V-expressing cell
      apoptosis in most (~75%) tumor cells, and provide evidence for phagocytosis of
      apoptotic tumor cells by flow cytometry and confocal microscopy. The DC-EG7/CD40L
      cells showed higher expression of DC maturation markers (Ia(b), CD40, CD80, and
      CD86) and peptide/major histocompatibility complex I than the control DC-EG7/Null
      cells. In addition, DC-EG7/CD40L vaccine stimulates more efficient (0.97%) tumor
      specific CTL responses than DC-EG7/Null cells (0.31%). Furthermore, 80% (4/5) of
      mice immunized with DC-EG7/CD40L vaccine become tumor-free after EG7 tumor cell
      challenge, whereas DC-EG7/Null vaccine only delays immunized mouse death.
      CONCLUSIONS: Dendritic cells that have phagocytized CD40L-expressing apoptotic
      tumor cells appear to offer new strategies in DC cancer vaccines.

PMID- 25983090
TI  - Supraclavicular and infraclavicular lymph node delineation in breast cancer
      patients: a proposal deriving from a comparative study.
AB  - AIMS AND BACKGROUND: Current advances in radiotherapy for breast cancer require
      knowledge of the anatomy of irradiated areas to minimize geographic miss and
      spare organs at risk. This study aimed at defining a contouring approach for
      supraclavicular (SC) and infraclavicular (IC) nodes after mastectomy or
      conservative surgery in patients with breast cancer. METHODS AND STUDY DESIGN: In
      15 patients, SC and IC nodes were contoured on computed tomography slices
      according to Madu et al and Dijkema et al. After analyzing relapse sites, as
      reported by Reed et al, our approach was defined. The 3 methods were compared in
      all patients, quantifying differences in contours by percentage overlap (PO).
      RESULTS: In our approach, SC node delineation is similar to Madu et al in the
      ventral and medial landmarks, but includes the lateral SC nodes described by
      Dijkema et al. The lateral landmarks are the scalenus anterior and medius muscle
      lateral border and the clavicle. Dorsal boundaries are the scalenus anterior and
      medius muscle ventral and lateral surfaces and the subclavian artery ventral
      border. In IC node delineation, major differences emerged in cranial and dorsal
      limits which, in our approach, are the pectoralis minor muscle upper edge and the
      subclavian axillary artery ventral side. Our mean and median volumes and POs were
      between the other 2 methods. CONCLUSIONS: This study contributes to standardizing
      draining node contouring, so as to reduce variability and minimize geographic
      miss.

PMID- 25983091
TI  - Clinical implications of serum hypoxia inducible factor-1alpha and vascular
      endothelial growth factor in lung cancer.
AB  - AIMS AND BACKGROUND: Hypoxia inducible factor 1alpha (HIF-1alpha) and vascular
      endothelial growth factor (VEGF) have been deemed as key in angiogenesis of lung
      cancer. The aim of this study was to investigate diagnostic and prognostic values
      of HIF-1alpha and VEGF in patients with lung cancer. METHODS: From May 1, 2011,
      to April 20, 2014, blood samples and/or pleural effusions were collected from 100
      patients with lung cancer, 18 patients with tuberculosis, 47 patients with
      community-acquired pneumonia, and 29 healthy controls. The pretreatment levels of
      HIF-1alpha and VEGF were measured by enzyme-linked immunoassays. Patients with
      lung cancer were followed up during the period of this study and survival times
      were recorded for analysis. RESULTS: We detected that the levels of serum and
      pleural HIF-1alpha in lung cancer were significantly higher than those in the
      tuberculosis population, and that the VEGF expressions were not significantly
      different between malignancy and benign diseases. An area under the curve of
      pleural HIF-1alpha (0.877 +/- 0.053) showed a high ability to differentiate lung
      cancer from benign diseases. The significant negative predictors of survival in
      the univariate analysis were performance status (gt;1), no anticancer therapy,
      low serum albumin, advanced stage, and serum high level of VEGF (gt;324.17
      pg/mL), while in the multivariate Cox regression analysis, only the pretreatment
      serum level of VEGF, stage, and anticancer therapy were identified as independent
      prognostic factors. CONCLUSIONS: The overexpression of HIF-1alpha especially in
      pleural effusion may be an angiogenic factor for distinguishing malignancy from
      tuberculosis, and the pretreatment level of serum VEGF may be an independent
      predictor of survival.

PMID- 25983092
TI  - Pathway crosstalk analysis of high-metastasis lung cancer cells.
AB  - BACKGROUND: The aim of this study was to investigate the important role of
      pathway crosstalk and pathway dysfunction in the high-metastasis process of lung
      cancer cells, by using the microarray expression profiles of lung cancer cells at
      different metastasis levels. METHODS: The gene expression profile GSE10096 was
      downloaded from the Gene Expression Omnibus database, including 4 nonmetastasis
      samples, 3 low-metastasis samples (M1) and 3 high-metastasis samples (M5) of lung
      cancer cells. After the conversion from probe level to expression values using
      Jetset, the data were identified by limma package in R language to screen
      differentially expressed genes (DEGs). The pathways of DEGs were further enriched
      by the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein
      interaction (PPI) network of genes related to the core pathway (pathway in
      cancer) and its neighbor pathways was constructed. Based on the PPI network,
      significantly changed pathway crosstalk and pathways were analyzed. RESULTS:
      Compared with those in the M1 lung cancer cells, the pathways hsa00564
      (glycerophospholipid metabolism) and hsa0098 (metabolism of xenobiotics by
      cytochrome P450) of the M5 lung cancer cells showed significant functional
      changes. The dysfunction of pathway crosstalk mainly occurred between pathways
      hsa0098 and hsa04916 (melanogenesis pathway) and other pathways. CONCLUSIONS: The
      results of our analysis indicate the significance of pathway crosstalk
      dysfunction and pathway dysfunction of M1 and M5 lung cancer cells as shown by
      bioinformatics methods. The present findings have the potential to lead to the
      study of the mechanisms of lung cancer in future.

PMID- 25983093
TI  - Very elderly (>80 years), frail patients with muscle-invasive bladder cancer and
      comorbidities: is curative irradiation feasible?
AB  - PURPOSE: To evaluate clinical results in elderly and frail patients with bladder
      cancer treated with curative conformal irradiation alone. METHODS: The records of
      ambulatory frail elderly patients, age >80 years, Charlson Comorbidity Index
      (CCI) >5, with invasive bladder cancer, were retrospectively analyzed. The
      patients were irradiated with curative intent. Acute and late toxicities were
      evaluated. RESULTS: A total of 27 ambulatory patients were treated. Median age
      was 84.5 years and a median CCI of 6.5 was recorded. Median delivered radiation
      dose was 64 Gy. All patients completed the planned treatment. Grade 1-2
      gastrointestinal (GI) and genitourinary (GU) toxicities were observed in 55.5% of
      patients (15/27). At the last follow-up, no late G3+ toxicities have been
      observed, with G1-2 toxicities reported in 11.1% of patients (3/27). Higher
      values of CCI were associated with higher acute GU/GI toxicities; there was a
      correlation between CCI and acute GU toxicity (r = 0.43, p = 0.027). The mean
      survival time was 23.5 months (95% confidence interval 20.9-26.1) and no median
      was reached. Locoregional disease-free events and metastasis-free survival showed
      a 2-year actuarial rate of 90% and 87%, respectively, with an actuarial 2-year
      overall survival of 84.5%. CONCLUSIONS: Our results demonstrate safety and
      feasibility of curative radiation therapy in very elderly and frail patients with
      bladder cancer using 3D conformal radiation therapy.

PMID- 25983094
TI  - Concurrent versus sequential chemoradiotherapy for esophageal cancer among
      Chinese population: a meta-analysis.
AB  - AIMS AND BACKGROUND: Esophageal cancer can cause substantial mortality and there
      is controversy about the effectiveness of concurrent and sequential
      chemoradiotherapy (CRT) for this disease. METHODS AND STUDY DESIGN: Based on
      established criteria, we searched electronic databases including PubMed, Excerpta
      Medica Database (Embase), China National Knowledge Infrastruction (CNKI),
      Wanfang, and Weipu databases up to March 2014 to collect eligible studies.
      Relative risks (RRs) and their 95% confidence intervals (CIs) were calculated. Q
      and I2 test were applied to test statistical heterogeneities among studies.
      Publication bias of total effective rate was evaluated through a funnel plot and
      sensitive analysis was conducted. RESULTS: We identified 10 Chinese studies
      including 1024 esophageal cancer patients. The RRs of total effective rate and 1
      , 2-, and 3-year survival rate for concurrent versus sequential CRT were 1.15
      (95% CI 1.07 to 1.24), 1.15 (95% CI 1.05 to 1.26), 1.44 (95% CI 1.21 to 1.73),
      and 1.66 (95% CI 1.37 to 2.01), respectively, all with statistically significant
      differences (p<0.05). With regards to incidence of leukocytopenia, the RR for
      concurrent versus sequential CRT was 1.14 (95% CI 1.03 to 1.26) with significant
      difference (p<0.05). However, the RR of incidence of radiation esophagitis was
      1.09 (95% CI 0.96 to 1.22) for concurrent versus sequential CRT without
      significant differences (p = 0.17). CONCLUSIONS: Concurrent CRT was superior to
      sequential CRT for esophageal cancer management among Chinese people. Though
      higher toxic effects were revealed in concurrent CRT, it was tolerable.
      Therefore, concurrent CRT could be applied into esophageal cancer treatments for
      Chinese patients.

PMID- 25983096
TI  - Smoking in Italy 2013-2014, with a focus on the young.
AB  - AIMS: To update smoking prevalence trends in Italy among adult and young
      populations; to determine the recent spread, particularly among young smokers, of
      roll-your-own (RYO) cigarettes (which cost approximately half the price of
      manufactured cigarettes); and to evaluate the effects of 2013 legislation
      increasing the minimum tobacco purchasing age from 16 to 18 years in Italy.
      METHODS: Two surveys on smoking were conducted in 2013 and 2014 in Italy, on a
      total sample of 6052 individuals, representative each year of the national
      population aged >=15 years, where we collected data on type of tobacco most
      frequently smoked and on the perception of the enforcement of the tobacco sales
      to-minors legislation. RESULTS: A total of 21.1% of the population surveyed were
      smokers (25.5% of men and 17.0% of women). Prevalence of current smoking among
      young participants (15-24 years) was 19.9% (21.7% of male participants and 18.0%
      of female participants). Overall, 6.9% of smokers, and 13.3% of young smokers,
      reported RYO cigarettes as the most frequently smoked tobacco product. More than
      80% of Italian adults had never seen a tobacco retailer refuse to sell cigarettes
      to minors (i.e., aged <18 years) or request their identification or age.
      CONCLUSIONS: Although adult and young smoking prevalence rates substantially
      decreased over the last few decades, neither of them have significantly changed
      since 2007. Use of RYO cigarettes is increasing, particularly among the young.
      Our study highlights the need to equalize the costs of different types of tobacco
      products and to improve the enforcement of the current tobacco sales-to-minors
      legislation.

PMID- 25983095
TI  - Docetaxel, capecitabine and concurrent radiotherapy for gastric cancer patients
      with postoperative locoregional recurrence.
AB  - AIMS AND BACKGROUND: This study aimed to assess the efficacy of concurrent
      chemoradiotherapy (CCRT) with docetaxel and capecitabine versus docetaxel and
      capecitabine chemotherapy for gastric cancer patients with postoperative
      locoregional recurrence. METHODS: From 2008 to 2011, 81 patients with
      locoregional recurrence after curative resection of gastric cancer were enrolled.
      Thirty-nine (CCRT group) received involved-field radiotherapy with oral
      capecitabine (twice daily, 5 days/week) and intravenous infusion of docetaxel
      (once weekly). The remaining 42 patients (chemotherapy group) were treated with
      oral capecitabine (twice daily, days 1-14) followed by intravenous infusion of
      docetaxel (days 1 and 8). The overall response rate, overall symptom control
      rate, toxicity or adverse reactions, and overall survival (OS) were compared.
      RESULTS: The overall response rate (CR+PR) was significantly higher in the CCRT
      group (79.5%) than the chemotherapy group (54.8%). In CCRT individuals, the
      control rates for bleeding, pain, and dysphagia/obstruction were 87.5%, 75%, and
      71.4%, respectively, versus 63.2%, 50%, and 28.6% in the chemotherapy group. CCRT
      patients had a better symptom control rate than the chemotherapy group (52.5% vs.
      80%). Adverse reactions were nonsignificantly more severe in CCRT patients.
      Finally, median OS was longer in the CCRT vs. chemotherapy group (14.2 vs. 6.4
      months). CONCLUSIONS: Involved-field radiotherapy with docetaxel and capecitabine
      was effective and well tolerated. These findings provide further insight into the
      role of CCRT in gastric cancer. However, this was not a randomized controlled
      study and the number of patients was relatively small, suggesting that cautious
      interpretation of cumulative estimates is warranted.

PMID- 25983097
TI  - Three-dimensional ultrasound-based target volume delineation and consequent dose
      calculation in prostate cancer patients with bilateral hip replacement: a report
      of 4 cases.
AB  - AIM: To investigate the role of 3D ultrasound (3D-US) in target volume
      delineation in prostate cancer radiotherapy. METHODS: Four patients with
      intermediate risk prostate cancer and metal artifacts on planning computed
      tomography (CT) due to previous bilateral hip replacement underwent 3D-US with
      the Clarity platform (Clarity System, Elekta, Stockholm, Sweden) to allow for
      image-guided procedures. Ultrasound and CT images were coregistered to allow for
      better delineation of the prostate gland and organs at risk (OAR). Electron
      density override (EDO) and standard electron density (EDS) methods were compared
      for appropriate dose calculation. RESULTS: 3D-US and planning CT minimized image
      artifacts, providing better evidence of patient anatomy, particularly regarding
      soft tissue visualization. Prostate gland and seminal vesicles were better
      delineated, particularly in the posterior aspect. Anterior rectal wall and
      bladder neck were more visible. No difference was found in terms of average
      planning target volume dose, D15%, or D25% for rectum or D15%, D25%, or D35% of
      bladder between EDO and EDS. CONCLUSIONS: 3D-US proved to be a viable tool for
      target volume and OAR visualization in patients with prostate cancer with hip
      prostheses.

PMID- 25983098
TI  - Evaluation of transforming growth factor-beta2 for radiation-induced diarrhea
      after pelvic radiotherapy.
AB  - AIMS AND BACKGROUND: Radiotherapy (RT) plays a central role in the management of
      cancers located in the abdomen and pelvis. However, radiation-induced toxicity
      remains a major concern for patients receiving RT to the abdominopelvic region.
      In this context, our study aims to evaluate the use of transforming growth factor
      (TGF)-beta2-enriched formula for amelioration of radiation-induced diarrhea for
      patients undergoing pelvic RT. METHODS AND STUDY DESIGN: Between September 2013
      and September 2014, 86 malnourished patients undergoing RT for pelvic cancers who
      received oral nutritional supplementation with or without TGF-beta2-enriched
      formula were assessed retrospectively in 3 groups. Oral diphenoxylate-atropine
      tablets were used at onset of diarrhea in all groups. Kruskal-Wallis and chi
      square tests were used in the comparison of continuous and categorical variables,
      respectively. RESULTS: Patients receiving nutritional supplemention with TGF
      beta2-enriched formula (groups I and II) experienced a significantly lower median
      number of diarrhea episodes compared to patients receiving nutritional
      supplementation with other products (group III), which was statistically
      significant (p<0.05). Also, number of patients experiencing grade 2 and grade 3
      diarrhea was significantly lower in groups I and II compared to group III
      (p<0.05). CONCLUSIONS: Nutritional supplemention with TGF-beta2-enriched formula
      offers amelioration of radiation-induced diarrhea for patients receiving pelvic
      RT. Since this is the first study assessing the use of nutritional
      supplementation with TGF-beta2-enriched formula for patients undergoing pelvic
      RT, future prospective studies are needed to confirm the results.

PMID- 25983099
TI  - Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT): a
      representative literature review occasioned by a rare IMT of the transverse colon
      in a 9-year-old child.
AB  - AIMS AND BACKGROUND: Inflammatory pseudotumor (IPT) and inflammatory
      myofibroblastic tumor (IMT) represent different entities. However, it is only in
      recent years that this has been taken into increasing consideration. Some authors
      still use both terms synonymously or interchangeably. Inflammatory
      myofibroblastic tumor is a real neoplasm because of the proliferation of
      myofibroblastic cells. Inflammatory pseudotumor is a more inflammatory reactive
      or regenerative entity and shows an overlapping with immunoglobulin G4-related
      disease. METHODS AND STUDY DESIGN: To analyze the current situation, 443
      publications from the last 5 years (2009 to February 2014) were included. Reports
      involved 938 patients and 956 organ sites. The age distribution is twin peaked
      with one maximum in childhood and the other between 50 and 60 years of age. This
      distribution is questionable due to the more frequent occurrence of IPT in the
      liver and of IMT in the lung. Inflammatory pseudotumors mainly occur in older
      patients; IMTs in children and young adults. RESULTS AND CONCLUSIONS: The liver
      and biliary tract were the most commonly affected of all body regions, at 32%.
      This was followed by the lung, including the respiratory tract, at 27%, and by
      the gastrointestinal tract, at 10%. Lesions of the large bowel, as in the present
      case of a 9-year-old boy, are very rare. There were organ-related as well as
      nonspecific clinical symptoms, such as fever, weight loss, and fatigue.
      Laboratory test results revealed anemia and elevated inflammation-dependent
      parameters. The patterns in medical imaging are variable and nonspecific.
      Morphology often suggests a malignant process. For this reason, therapy in most
      cases is surgical, but this is required more often in IMTs. Many IPTs could be
      treated conservatively.

PMID- 25983100
TI  - Evaluation of melanoma features and their relationship with nodal disease: the
      importance of the pathological report.
AB  - BACKGROUND: The pathological features of melanoma biopsies can provide
      significant prognostic information that can help the surgeon evaluate the risk of
      nodal disease. The aim of this study was to attempt to determine the relationship
      between pathological features of primary melanoma and nodal disease, by sentinel
      node biopsy (SNB) and complete node dissection (CND). METHODS: A retrospective
      analysis was completed of patients who underwent SNB at AC Camargo Cancer Center,
      Sao Paulo, Brazil, between 2000 and 2010. RESULTS: A total of 697 patients were
      evaluated. By univariate analysis, it was found that histology, Clark level,
      Breslow depth, mitotic index, ulceration, regression, lymphatic and perineural
      invasion and satellitosis were significantly associated with SNB positivity. In
      the multivariate analysis, it was found that Breslow depth, mitotic index,
      ulceration, regression, lymphatic invasion and satellitosis were significant
      factors. In patients with a positive SNB, the primary tumor site, Clark level and
      Breslow depth greater than 2 mm were significantly related to non-sentinel node
      (NSN) positivity by univariate analysis. By multivariate analysis, Breslow depth
      greater than 2 mm was the only primary tumor feature that was significantly
      related (p = 0.038). CONCLUSIONS: The indication of SNB should not be based
      solely on Breslow depth and ulceration or mitotic index. A complete evaluation of
      the pathological report should improve the identification of high-risk patients.

PMID- 25983102
TI  - Primary mucosal malignant melanoma of the cervix: case report and review of the
      literature.
AB  - The incidence of primary mucosal malignant melanoma (PMMM) is 1.3% among all
      malignant melanomas (MM). Cervical involvement is very rare; the number of cases
      of cervical PMMM reported so far is around 80. In our patient, a dark color, 2-cm
      diameter, nonulcerated tumor formation was observed upon examination of the
      cervix. Tumoral tissue consisted of atypical melanocytic cells containing
      numerous mitotic figures. In immunochemical studies, S-100, Melan-A, and HMB-45
      positivity were observed. The tumor was 20 mm in invasion depth, Breslow IV, and
      FIGO stage IB1. Radical surgery was followed by adjuvant radiotherapy, and
      subsequently interferon treatment was applied. Examination and scans 20 months
      after surgery were free from tumor. 

PMID- 25983101
TI  - ANXA1 silencing increases the sensitivity of cancer cells to low-concentration
      arsenic trioxide treatment by inhibiting ERK MAPK activation.
AB  - AIMS AND BACKGROUND: Arsenic trioxide (ATO), an antitumor agent, is widely used
      for treating acute promyelocytic leukemia (APL), in which it induces apoptosis.
      In most solid tumors, ATO disturbs the cell cycle instead of inducing apoptosis.
      We aimed to determine the exact mechanism underlying the different response of
      APL to ATO compared with the response of solid tumors. METHODS: A proteomics
      based screening was used to identify the ATO-associated proteins in the human
      esophageal squamous cell carcinoma cell line, Eca109. The expression levels of
      Annexin A1 (ANXA1) in 4 different types of cancer cells were determined by
      quantitative reverse transcription polymerase chain reaction and Western
      blotting. Human esophageal squamous cell carcinoma cell line Eca109 and
      pancreatic carcinoma cell line BxPC3 cells were transfected with siRNAs targeting
      ANXA1 and scrambled control siRNA. Cell proliferation was evaluated by methyl
      thiazolyl tetrazolium assay. RESULTS: After verification of the mRNA and protein
      levels in 4 cancer cell lines, ANXA1 and lamin A/B were validated to have
      increased expression levels after low-concentration ATO treatment. Lower
      concentrations of ATO, which has no effect on proliferation of cancer cells,
      induced apoptosis after ANXA1 silencing. Furthermore, overexpression of ANXA1
      induced by ATO resulted in activation of extracellular signal-regulated kinase
      (ERK) mitogen-activated protein kinases (MAPKs), rendering cancer cells resistant
      to the agent. In addition, PD98059, a specific ERK inhibitor, increased the
      sensitivity of cancer cells to a lower concentration of ATO treatment.
      CONCLUSIONS: Taken together, these data indicate that overexpression of ANXA1
      induced by low-concentration ATO makes cancer cells more resistant to the agent
      via activated ERK MAPKs. Specific silencing of ANXA1 increased the sensitivity of
      cancer cells to ATO treatment.

PMID- 25983104
TI  - Host preferences of immature Dermacentor reticulatus (Acari: Ixodidae) in a
      forest habitat in Germany.
AB  - Dermacentor reticulatus is widespread throughout Europe and is expanding its
      range in several European countries. It is associated with a number of different
      pathogens. Its role in the transmission of disease to humans is currently small;
      however, it might play an important role in the maintenance of pathogens in
      enzootic cycles. The ecology of D. reticulatus, especially of the immatures, is
      not well known. In this study, ticks from small mammals, caught in a capture-mark
      release study between May 2012 and October 2014 in a unique woodland area close
      to Karlsruhe, Germany, were collected. The main host species trapped were the
      yellow-necked mouse (Apodemus flavicollis) and the bank vole (Myodes glareolus).
      Small mammal populations showed high variability in their density between the
      study years, which is probably due to harsh winter conditions in 2012/2013 and
      missing mast leading to high winter mortality. Larvae and nymphs of D.
      reticulatus were predominantly found in July and August, respectively, and the
      infestation rates among the different small mammal species suggest a host
      preference of D. reticulatus for M. glareolus. 

PMID- 25983103
TI  - Radiotherapy for head and neck cancer in Lombardy: a survey by the Lombardy Group
      of the Italian Association for Radiation Oncology.
AB  - AIMS: In 2013, a survey was conducted to analyze the available resources and
      their use in the radiation treatment of patients with malignancies of the head
      and neck region in Lombardy, on behalf of the Lombardy group of the Italian
      Association of Radiation Oncology. METHODS: A questionnaire was sent to 26 of 34
      radiotherapy centers active in the region. Two centers were excluded because they
      did not treat head and neck cancers (Besta Neurological Institute and Cyberknife
      center), 4 had started their activity in 2013 or late 2012, and 2 satellite
      centers had their results included in the main center's response. Items
      investigated included number of patients with head and neck cancer treated in
      2012, general technical issues, and integration with surgery and chemotherapy.
      RESULTS: Twenty-four questionnaires were returned (92% response rate). There was
      a good consistency on the use of radiotherapy in different settings, whereas
      integration with chemotherapy showed more heterogeneous data. Treatment
      techniques were 3D conformal radiotherapy or intensity-modulated radiotherapy
      with image-guided radiotherapy in most cases and a low rate of treatment-related
      death was observed. CONCLUSIONS: This survey provides important data on the use
      of radiotherapy resources for patients with head and neck cancer in Lombardy. The
      data offer the opportunity to further investigate issues that could better
      standardize head and neck cancer treatment and allocate resources across the
      region.

PMID- 25983105
TI  - EMPIRE: a highly parallel semiempirical molecular orbital program: 2: periodic
      boundary conditions.

PMID- 25983106
TI  - A comprehensive analysis of P...pi pnicogen bonds: substitution effects and
      comparison with Br...pi halogen bonds.
AB  - Ab initio calculations were carried out in a systematic investigation of P...pi
      pnicogen-bonded complexes XH2P...C2H2/C2H4 and FH2P...C2R2/C2R4 for X = H, CH3,
      OH, CN, Br, Cl, NO2, F, and R = F, CH3, as well as corresponding Br...pi halogen
      bonded complexes XBr...C2H2. Both the electron-withdrawing and electron-donating
      substituents in the electron acceptor have enhancing effects on the strength of
      P...pi interactions. The electron-donating group in the electron donor leads to
      strengthening while the electron-withdrawing group leads to weakening of P...pi
      interactions. The studied P...pi and Br...pi interactions are similar and are
      typically "closed-shell" non-covalent character in nature. Moreover, analyses of
      natural bond orbital and density difference of molecular formation indicated that
      charge transfer and polarization also play important roles in P...pi
      interactions. The substituents have direct effects on the molecular electrostatic
      potential, and the charge transfer amount and extent of polarization of the
      P...pi interaction are also specific to each substituent. 

PMID- 25983107
TI  - Identification of microRNAs associated with sexual maturity in rainbow trout
      brain and testis through small RNA deep sequencing.
AB  - MicroRNAs are ubiquitous, short, non-coding RNA molecules that function as post
      transcriptional regulators of gene expression in a variety of biological
      processes. In order to further our understanding of the microRNA hierarchy in the
      reproductive axis of male teleosts, four small RNA libraries were constructed,
      and sequenced from the testis and brain of sexually mature adults and immature
      juvenile rainbow trout (Oncorhynchus mykiss) using Illumina small-RNA deep
      sequencing. We obtained 56,632,987; 39,870,661; 82,454,370; and 53,143,465 high
      quality, filtered reads for immature testis, mature testis, immature brain, and
      mature brain, respectively. Among the libraries, 433 known mature piscine miRNAs
      were identified, with 124 and 116 significantly differentially expressed miRNAs
      found between sexually immature/mature testes and immature/mature brain tissues,
      respectively. Among these differentially expressed miRNAs, miR-129, -130c, -135b,
      -140, -146a, -192, -199a, -16, and, -19b showed higher abundance in the testis
      whereas miR-10b, -183, -199, -375, -1937, and miR-nov210 were more abundant in
      the brain. In silico target prediction of these differentially expressed miRNAs
      suggested their putative roles in the sexual maturation of male rainbow trout.

PMID- 25983108
TI  - Nanosized microporous crystals: emerging applications.
AB  - This review highlights recent developments in the synthesis and unconventional
      applications of nanosized microporous crystals including framework (zeolites) and
      layered (clays) type materials. Owing to their microporous nature nanosized
      zeolites and clays exhibit novel properties, different from those of bulk
      materials. The factors controlling the formation of nanosized microporous
      crystals are first revised. The most promising approaches from the viewpoint of
      large-scale production of nanosized zeolites and clays are discussed in depth.
      The preparation and advanced applications of nanosized zeolites and clays in free
      (suspension and powder forms) and fixed (films) forms are summarized. Further the
      review emphasises the non-conventional applications of new porous materials. A
      comprehensive analysis of the emerging applications of microporous nanosized
      crystals in the field of semiconductor industry, optical materials, chemical
      sensors, medicine, cosmetics, and food industry is presented. Finally, the future
      needs and perspectives of nanosized microporous materials (zeolites and clays)
      are addressed. 

PMID- 25983109
TI  - Intravitreal aflibercept for ranibizumab-resistant exudative age-related macular
      degeneration with choroidal vascular hyperpermeability.
AB  - PURPOSE: To investigate anatomical responses and visual changes in cases of
      exudative age-related macular degeneration (AMD) with choroidal vascular
      hyperpermeability (CVH) that responded poorly to multiple ranibizumab injections
      and were treated with intravitreal aflibercept. DESIGN: Retrospective comparative
      study. PARTICIPANTS: Twenty-five consecutive patients attending the outpatient
      clinic of the University of Tokyo Hospital who showed an insufficient response to
      multiple intravitreal ranibizumab injections and were switched to intravitreal
      aflibercept injections between March and June 2013. All patients were treated
      with intravitreal aflibercept in a treat-and-extend regimen and followed up for
      at least 12 months. METHODS: Presence or absence of CVH was determined by
      indocyanine green angiography. Changes of best-corrected visual acuity (BCVA) and
      central retinal thickness (CRT) at 12 months were compared between the CVH (+)
      AMD and CVH (-) AMD eyes. RESULTS: The improvement in logMAR BCVA at 12 months
      was larger in the CVH (-) AMD eyes than in the CVH (+) AMD eyes (-0.18 vs -0.026;
      P = 0.0089, t-test). The changes in CRT did not differ significantly between the
      groups (-122 +/- 101 MUm in the CVH (-) AMD eyes and -159 +/- 118 MUm in the CVH
      (+) AMD eyes; P = 0.44, t-test). The proportion of the eyes without intraretinal
      or subretinal fluid or hemorrhage was 88% in the CVH (-) AMD and 67% in the CVH
      (+) AMD (P = 0.21, t-test). CONCLUSIONS: Compared with AMD without CVH, AMD with
      CVH showed poorer visual gain resulting from intravitreal aflibercept treatment.

PMID- 25983110
TI  - A conserved WW domain-like motif regulates invariant chain-dependent cell-surface
      transport of the NKG2D ligand ULBP2.
AB  - Malignant cells expressing NKG2D ligands on their cell surface can be directly
      sensed and killed by NKG2D-bearing lymphocytes. To ensure this immune
      recognition, accumulating evidence suggests that NKG2D ligands are trafficed via
      alternative pathways to the cell surface. We have previously shown that the NKG2D
      ligand ULBP2 traffics over an invariant chain (Ii)-dependent pathway to the cell
      surface. This study set out to elucidate how Ii regulates ULBP2 cell-surface
      transport: We discovered conserved tryptophan (Trp) residues in the primary
      protein sequence of ULBP1-6 but not in the related MICA/B. Substitution of Trp to
      alanine resulted in cell-surface inhibition of ULBP2 in different cancer cell
      lines. Moreover, the mutated ULBP2 constructs were retained and not degraded
      inside the cell, indicating a crucial role of this conserved Trp-motif in
      trafficking. Finally, overexpression of Ii increased surface expression of wt
      ULBP2 while Trp-mutants could not be expressed, proposing that this Trp-motif is
      required for an Ii-dependent cell-surface transport of ULBP2. Aberrant soluble
      ULBP2 is immunosuppressive. Thus, targeting a distinct protein module on the
      ULBP2 sequence could counteract this abnormal expression of ULBP2.

PMID- 25983111
TI  - The function of ultra-large von Willebrand factor multimers in high shear flow
      controlled by ADAMTS13.
AB  - The paradigm that platelet aggregation, which contributes to bleeding arrest and
      also to thrombovascular disorders, initiates after signaling-induced platelet
      activation has been refuted in past recent years. Platelets can form aggregates
      independently of activation when soluble von Willebrand factor (VWF) is present
      and the shear rate exceeds a certain threshold where active A1 domains become
      exposed in soluble VWF multimers and can bind to platelet glycoprotein Ib.
      Subsequently - fostering each other - VWF can self-assemble into large nets
      combining with platelets into large conglomerates, which are entirely reversible
      when they enter a flow region with shear rates below the threshold. In addition
      the threshold changes from approximately 20 000 s-1 in wall parallel flow to
      approximately 10 000 s-1 in stagnation point flow. VWF containing ultra-large
      multimers - as when just released from endothelial storage sites - has been shown
      to have the highest binding potential to platelets and to each other, thus
      facilitating rapid platelet accrual to sites of vessel injury and exposed
      subendothelial structures, i.e. collagen. The VWF nets as well as the platelet
      VWF conglomerates are controlled by the cleaving protease ADAMTS13 within minutes
      under high shear flow. Therewith the hemostatic potential is delivered where
      needed and the thrombogenic potential is highly controlled twofold: by flow and
      enzymatic proteolytic cleavage.

PMID- 25983112
TI  - The walk-bicycle: A new assistive device for Parkinson's patients with freezing
      of gait?
AB  - BACKGROUND: Previous studies reported a preserved ability to cycle in freezers,
      creating opportunities for restoring mobility and independence. However, use of a
      bicycle is not always feasible. Here, we investigated the effectiveness of a
      "walk-bicycle" in reducing freezing of gait (FOG). METHODS: Eighteen Parkinson
      patients with FOG performed the following tasks, each four times, with and
      without the walk-bicycle: (1) normal walking; (2) walking with small steps, at
      normal speed; (3) walking with small steps, as rapidly as possible. RESULTS:
      Seven patients showed FOG during walking without the walk-bicycle. In those
      patients, the walk-bicycle afforded a 12% reduction of time frozen (p = 0.026).
      In 11 patients no FOG was observed during walking without the walk-bicycle. Two
      of them showed FOG when using the walk-bicycle. CONCLUSIONS: The walk-bicycle may
      help to reduce FOG in some patients, but not in all. Future studies need to
      evaluate its usefulness in a home environment.

PMID- 25983113
TI  - Mechanistic basis of adaptive maternal effects: egg jelly water balance mediates
      embryonic adaptation to acidity in Rana arvalis.
AB  - Environmental stress, such as acidification, can challenge persistence of natural
      populations and act as a powerful evolutionary force at ecological time scales.
      The ecological and evolutionary responses of natural populations to environmental
      stress at early life-stages are often mediated via maternal effects. During early
      life-stages, maternal effects commonly arise from egg coats (the extracellular
      structures surrounding the embryo), but the role of egg coats has rarely been
      studied in the context of adaptation to environmental stress. Previous studies on
      the moor frog Rana arvalis found that the egg coat mediated adaptive divergence
      along an acidification gradient in embryonic acid stress tolerance. However, the
      exact mechanisms underlying these adaptive maternal effects remain unknown. Here,
      we investigated the role of water balance and charge state (zeta potential) of
      egg jelly coats in embryonic adaptation to acid stress in three populations of R.
      arvalis. We found that acidic pH causes severe water loss in the egg jelly coat,
      but that jelly coats from an acid-adapted population retained more water than
      jelly coats from populations not adapted to acidity. Moreover, embryonic acid
      tolerance (survival at pH 4.0) correlated with both water loss and charge state
      of the jelly, indicating that negatively charged glycans influence jelly water
      balance and contribute to embryonic adaptation to acidity. These results indicate
      that egg coats can harbor extensive intra-specific variation, probably
      facilitated in part via strong selection on water balance and glycosylation
      status of egg jelly coats. These findings shed light on the molecular mechanisms
      of environmental stress tolerance and adaptive maternal effects. 

PMID- 25983114
TI  - Diet specialization in a generalist population: the case of breeding great tits
      Parus major in the Mediterranean area.
AB  - The analysis of diet specialization provides key information on how different
      individuals deal with similar food and habitat constraints within populations.
      Characterizing parental diet specialization at the moment of breeding, and the
      consistency of these preferences under different levels of effort, may help us to
      understand why parents exploit alternative resources. We investigated these
      questions in a species commonly considered a generalist: a breeding population of
      Mediterranean great tits Parus major. Our aim was to determine whether they are
      specialists or generalists at the pair level, and the consistency of this
      behaviour under different levels of effort. Using proportional similarity and
      mean pairwise overlap indices, we found that parents showed great variability in
      prey selection between territories. That is, they displayed a small niche
      overlap. Interestingly, the most specialized breeding pairs showed a tendency to
      have larger broods. Additionally, we experimentally manipulated brood size and
      found that parents showed high short-term consistency in their foraging
      behaviour. They precisely adjusted the number of provisioning trips to the number
      of nestlings, while they were unable to modify prey proportions or prey size
      after brood size was changed. We can therefore characterize their foraging
      strategies as highly consistent. Our results suggest that although the great tit
      may be considered a generalist at the species or population level, there was a
      tendency for trophic specialization among breeding pairs. This high inter- and
      intrapopulation plasticity could account for their great success and wide
      distribution. 

PMID- 25983115
TI  - Effect of irrigation fluid temperature on core body temperature and inflammatory
      response during arthroscopic shoulder surgery.
AB  - PURPOSE: This study was designed to evaluate the influence of irrigation fluid on
      the patients' physiological response to arthroscopic shoulder surgery. METHODS:
      Patients who were scheduled for arthroscopic shoulder surgery were prospectively
      included in this study. They were randomly assigned to receive warm arthroscopic
      irrigation fluid (Group W, n = 33) or room temperature irrigation fluid (Group
      RT, n = 33) intraoperatively. Core body temperature was measured at regular
      intervals. The proinflammatory cytokines TNF-alpha, IL-1, IL-6, and IL-10 were
      measured in drainage fluid and serum. RESULTS: The changes of core body
      temperatures in Group RT were similar with those in Group W within 15 min after
      induction of anesthesia, but the decreases in Group RT were significantly greater
      after then. The lowest temperature was 35.1 +/- 0.4  degrees C in Group RT and
      35.9 +/- 0.3  degrees C in Group W, the difference was statistically different (P
      < 0.05). Hypothermia occurred in 31 out of 33 subjects in Group RT (31/33; 94 %),
      but was significantly lower in Group W (9/24; 27 %; P < 0.05). Serum TNF-alpha
      changes were undetectable postoperatively. No statistical significant differences
      in serum IL-1 and serum IL-10 levels were observed between groups. Serum IL-6
      levels were significantly lower in Group W (P < 0.05). The levels of the above
      cytokines in drainage fluid were all significantly lower in Group W after surgery
      (P < 0.05). CONCLUSION: Hypothermia occurs more often in arthroscopic shoulder
      surgery by using room temperature irrigation fluid compared with warm irrigation
      fluid. And local inflammatory response is significantly reduced by using warm
      irrigation fluid. It seems that warm irrigation fluid is more recommendable for
      arthroscopic shoulder surgery.

PMID- 25983116
TI  - Quercetin protects necrotic insult and promotes apoptosis by attenuating the
      expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells.
AB  - The receptor for advanced glycation end-products (RAGE) is a multiligand member
      of the immunoglobulin superfamily, which plays an important role in maintaining
      cellular homeostasis. It is normally expressed on immune cells, including
      macrophages, monocytes, dendritic cells and T cells to maintain homeostasis, but
      highly upregulated at sites of vascular pathology. Accumulating evidence suggest
      that the elevated expression of RAGE and its ligand HMGB-1 was found in various
      types of cancer. The accumulation of RAGE and its ligand high-mobility group box
      proteins-1 (HMGB1) activates complex signaling network for cell survival and
      evades apoptosis. Therefore, targeting the RAGE-mediated signaling could be the
      promising strategies for the therapeutic potential of cancer. This study was
      aimed to examine the biological potential of quercetin on the regulation of RAGE-
      and HMGB1-mediated activation of NF-kappaB and induction of apoptotic cell death
      in MCF-7 cells. Our findings demonstrate that quercetin inhibits the expression
      of RAGE and HMGB1 in MCF-7 cells. In addition, quercetin protects necrotic insult
      and augments apoptosis in MCF-7 cells. Taken together, these results suggest that
      quercetin plays an important role in modulating RAGE and HMGB1 signaling and
      induces apoptotic cell death in MCF-7 cells.

PMID- 25983117
TI  - A population-based study of progression to metastatic prostate cancer in
      Australia.
AB  - BACKGROUND: We used population-based data from the New South Wales Central Cancer
      Registry (CCR) to describe the patterns of progression to metastatic disease in
      Australian men diagnosed with non-metastatic prostate cancer. METHODS: Data for
      all non-metastatic prostate cancer cases diagnosed 1993-2002 and followed to the
      end of 2007 were analysed. The outcome was progression to metastatic disease,
      identified by metastatic episode notifications in the CCR or by prostate cancer
      death. Factors associated with metastatic disease progression were identified
      using Cox regression models. RESULTS: Of the 32,643 men with non-metastatic
      prostate cancer at diagnosis 43.1% had localised disease, 5.1% had regional
      spread and 51.9% had unknown stage. After a median of 6.8 years of follow-up 6708
      cases (20.6%) had developed distant metastases. The risk of developing metastatic
      disease was significantly higher for those with regional (adjusted HR=2.65, 95%
      CI: 2.40-2.93) or unknown initial stage (adjusted HR=1.70, 95% CI: 1.61-1.80),
      for older men (65-74 years: HR=1.43, 95% CI: 1.33-1.53; >74 years: HR=2.73, 95%
      CI: 2.55-2.93), and those living in inner regional (HR=1.11, 95% CI: 1.04-1.18)
      or rural areas (HR=1.24, 95% CI: 1.14-1.36) or more disadvantaged areas (middle
      tertile: HR=1.09, 95% CI: 1.02-1.16; most disadvantaged: HR=1.12, 95% CI: 1.04
      1.19). The risk of developing metastatic disease decreased over calendar time
      (adjusted HR=0.98, 95% CI: 0.97-0.99 per year). CONCLUSIONS: After a median
      follow-up of 6.8 years more than 1 in 5 men diagnosed with non-metastatic
      prostate cancer developed distant metastases. This estimate of the overall risk
      of developing metastatic disease in the population, and the geographical
      disparities identified, can inform the planning of required cancer services.

PMID- 25983118
TI  - Waxman et al in NEJM does not disprove defensive practices in the ED.

PMID- 25983119
TI  - A comparison of the ETView VivaSight SL against a fiberoptic bronchoscope for
      nasotracheal intubation of multitrauma patients during resuscitation. A
      randomized, crossover, manikin study.

PMID- 25983120
TI  - Hounsfield units in pseudosubarachnoid hemorrhage-an old yet fascinating tool.

PMID- 25983121
TI  - Esophageal dissecans: a rare life-threatening presentation of recurrent pemphigus
      vulgaris.
AB  - Esophagitis dissecans superficialis (EDS) is a rare condition characterized by
      sloughing of the mucosal layer of the esophageal lining, usually triggered by an
      environmental/immune insult. It is associated with blistering diseases such as
      pemphigus vulgaris (PV), bullous pemphigoid, and epidermolysis bullosa. Oral
      mucosa is the most commonly (50%) affected site in PV, but esophageal involvement
      has only been rarely reported. The most common presentation of EDS includes
      dysphagia and odynophagia, but overt gastrointestinal bleeding is a distinctly
      uncommon. We present a unique case of EDS presenting with melena in which
      diagnostic endoscopy enabled to diagnose and establish link with patient's remote
      history of PV. Early suspicion and identification of this treatable condition can
      reduce morbidity and mortality in these patient populations by decreasing
      severity and recurrence of bleeding.

PMID- 25983122
TI  - Acute neurocysticercosis presenting as suicidal ideation.
AB  - This is a case of a 36-year-old Spanish-speaking Hispanic man who was brought to
      a busy suburban New Jersey emergency department (ED) by family members for
      altered mental status. By report, patient was noted by family to be "not acting
      normal" at home, when he went into his bathroom and locked the door. A brief time
      thereafter, he emerged smelling of bleach and with confused speech. The family
      surmised that he tried to commit suicide by drinking bleach and emergently
      brought the patient to the ED.

PMID- 25983123
TI  - Validation of the SYNTAX revascularization index to quantify reasonable level of
      incomplete revascularization after percutaneous coronary intervention.
AB  - Incomplete revascularization is common after percutaneous coronary intervention
      (PCI). Whether a "reasonable" degree of incomplete revascularization is
      associated with a similar favorable long-term prognosis compared with complete
      revascularization remains unknown. We sought to quantify the proportion of
      coronary artery disease burden treated by PCI and evaluate its impact on outcomes
      using a new prognostic instrument-the Synergy Between PCI with Taxus and Cardiac
      Surgery (SYNTAX) Revascularization Index (SRI). The baseline SYNTAX score (bSS),
      the residual SYNTAX score, and the delta SYNTAX score (DeltaSS) were determined
      from 888 angiograms of patients enrolled in the prospective SYNTAX trial. The SRI
      was then calculated for each patient using the following formula: SRI =
      (DeltaSS/bSS]) * 100. Outcomes were examined according to the proportion of
      revascularized myocardium (SRI = 100% [complete revascularization], 50% to <100%,
      and <50%). The Youden index for the SRI was computed to identify the best cutoff
      for 5-year all-cause mortality. The mean bSS was 28.4 +/- 11.5, and after PCI,
      the mean DeltaSS was 23.8 +/- 10.9 and the mean residual SYNTAX score was 4.5 +/-
      6.9. The mean SRI was 85.3 +/- 21.2% and was 100% in 385 patients (43.5%), <100%
      to 50% in 454 patients (51.1%), and <50% in 48 patients (5.4%). Five-year adverse
      outcomes, including death, were inversely proportional to the SRI. An SRI cutoff
      of <70% (present in 142 patients [16.0%] after PCI) had the best prognostic
      accuracy for prediction of death and, by multivariable analysis, was an
      independent predictor of 5-year mortality (hazard ratio [HR] 4.13, 95% confidence
      interval [CI] 2.79 to 6.11, p <0.0001). In conclusion, the SRI is a newly
      described method for quantifying the proportion of coronary artery disease burden
      treated by PCI. The SRI is a useful tool in assessing the degree of
      revascularization after PCI, with SRI >=70% representing a "reasonable" goal for
      patients with complex coronary artery disease. 

PMID- 25983124
TI  - Reply: To PMID 25499404.

PMID- 25983125
TI  - Comparison of outcomes and presentation in men-versus-women with bicuspid aortic
      valves undergoing aortic valve replacement.
AB  - Gender disparities in short- and long-term outcomes have been documented in
      cardiac and valvular heart surgery. However, there is a paucity of data regarding
      these differences in the bicuspid aortic valve (BAV) population. The aim of this
      study was to examine gender-specific differences in short- and long-term outcomes
      after surgical aortic valve (AV) replacement in patients with BAV. A
      retrospective analysis was performed in 628 consecutive patients with BAV who
      underwent AV surgery from April 2004 to December 2013. To reduce bias when
      comparing outcomes by gender, propensity score matching obtained on the basis of
      potential confounders was used. Women with BAV who underwent AV surgery presented
      with more advanced age (mean 60.7 +/- 13.8 vs 56.3 +/- 13.6 years, p <0.001) and
      less aortic regurgitation (29% vs 44%, p <0.001) and had a higher risk for in
      hospital mortality (mean Ambler score 3.4 +/- 4.4 vs 2.5 +/- 4.0, p = 0.015).
      After propensity score matching, women received more blood products
      postoperatively (48% vs 34%, p = 0.028) and had more prolonged postoperative
      lengths of stay (median 5 days [interquartile range 5 to 7] vs 5 days
      [interquartile range 4 to 6], p = 0.027). Operative, discharge, and 30-day
      mortality and overall survival were not significantly different. In conclusion,
      women with BAV who underwent AV surgery were older, presented with less aortic
      regurgitation, and had increased co-morbidities, lending higher operative risk.
      Although women received more blood products and had significantly longer lengths
      of stay, short- and long-term outcomes were similar.

PMID- 25983126
TI  - Earlobe crease shapes and cardiovascular events.
AB  - Earlobe crease (ELC) has been linked to coronary artery disease; however,
      systematic evaluations of the earlobe and its relation to ischemic stroke are
      lacking. The objectives were to define the ELC using a single-blind approach and
      to determine through multivariate analysis its association with cardiovascular
      events (CVEs) comprising coronary, ischemic cerebrovascular, and peripheral
      vascular diseases. A single-blind cross-sectional study was performed in 2
      phases: (1) an initial study (n = 300) to define ELC classification criteria and
      (2) a confirmation stage (n = 1,000) to analyze ELC association with CVEs. Each
      of the participants' pinnae were photographed and classified blindly by joint
      decision according to ELC's inclination, length, depth, and bilateralism.
      Patients' medical histories were reviewed for age, cardiovascular risk factors,
      and CVEs. The concordance rate after the classification of all photographs was
      89.6%. The first phase did not find any correlation between the different depth
      degrees or vertical creases and CVEs. The second stage concluded that diagonal
      bilateral ELC prevalence in patients with CVEs was 43% compared with 29% in the
      control patients (p <0.001). The multivariate analysis showed an association
      between ELC and CVEs (odds ratio 1.45, 95% confidence interval [CI] 1.08 to 1.93,
      p = 0.012), with a sensitivity and specificity of 43% and 70%, respectively.
      Ischemic stroke alone was also associated with diagonal bilateral ELC (odds ratio
      1.67, 95% confidence interval 1.1 to 2.51, p = 0.015). In conclusion, diagonal
      bilateral ELC is independently associated with CVEs in the hospitalized
      population. An independent association with ischemic stroke has also been
      demonstrated for the first time.

PMID- 25983127
TI  - Importance and feasibility of creating hypertrophic cardiomyopathy centers in
      developing countries: the experience in India.
AB  - Hypertrophic cardiomyopathy (HC) is a relatively common genetic heart disease
      responsible for mortality and morbidity at all ages. Using contemporary treatment
      advances, such as implantable defibrillators, surgical myectomy, heart
      transplant, and modern defibrillation for out-of-hospital cardiac arrest, it is
      now possible to reduce HC-related mortality considerably to 0.5% per year, less
      than expected in the general US adult population. However, in much of the
      developing world, HC has not yet become a priority given the many other cardiac
      conditions, such as coronary artery disease and systemic hypertension, so
      prevalent in the most populous countries such as China and India. Management of
      HC is best achieved in dedicated centers within institutions, such as previously
      demonstrated in the United States, Canada, some European countries, and
      Australia. This model has recently been introduced for the first time in India at
      the Amrita Institute of Medical Sciences and Research in Kochi, Kerala, in which
      a robust program focused on HC has emerged. This novel initiative, created
      despite the many obstacles in the Indian health care system, is an important step
      forward and is reported here detail. 

PMID- 25983128
TI  - Comparison of Contrast Volume, Radiation Dose, Fluoroscopy Time, and Procedure
      Time in Previously Published Studies of Rotational Versus Conventional Coronary
      Angiography.
AB  - Conventional coronary angiography (CA) with static imaging is limited by the
      ability to properly select the optimal acquisition angle, vessel foreshortening,
      and significant radiation exposure. Rotational coronary angiography (RA) acquires
      coronary images in a multitude of viewing angles during a single injection by
      means of a moving gantry that rapidly completes a predefined arc. This study
      compares procedural characteristics of CA and RA. Electronic search of databases
      such as OVID, Medline, and PubMed was conducted to identify studies comparing
      procedural characteristics of CA and RA. End points for analysis included
      contrast volume, radiation dose by dose area product, radiation dose by air
      kerma, fluoroscopy time, and procedure time. Studies were assessed for quality
      and bias and were included if they compared coronary imaging of both the right
      and left coronary systems with CA and RA, included one of the end points of
      interest, and were in English. A total of 11 studies consisting of 940 patients
      who underwent RA and 976 who underwent CA were included in the final analysis.
      Contrast volume, radiation dose by dose area product, and radiation dose by air
      kerma were all found to be significantly lower with RA compared with CA. There
      was a statistically significant increase in fluoroscopy time, although this was
      not clinically significant, and there was no difference in procedure time. RA
      angiography is a feasible alternative to CA and offers reductions in contrast
      used and radiation exposure. 

PMID- 25983129
TI  - Biodiversity mediates top-down control in eelgrass ecosystems: a global
      comparative-experimental approach.
AB  - Nutrient pollution and reduced grazing each can stimulate algal blooms as shown
      by numerous experiments. But because experiments rarely incorporate natural
      variation in environmental factors and biodiversity, conditions determining the
      relative strength of bottom-up and top-down forcing remain unresolved. We
      factorially added nutrients and reduced grazing at 15 sites across the range of
      the marine foundation species eelgrass (Zostera marina) to quantify how top-down
      and bottom-up control interact with natural gradients in biodiversity and
      environmental forcing. Experiments confirmed modest top-down control of algae,
      whereas fertilisation had no general effect. Unexpectedly, grazer and algal
      biomass were better predicted by cross-site variation in grazer and eelgrass
      diversity than by global environmental gradients. Moreover, these large-scale
      patterns corresponded strikingly with prior small-scale experiments. Our results
      link global and local evidence that biodiversity and top-down control strongly
      influence functioning of threatened seagrass ecosystems, and suggest that
      biodiversity is comparably important to global change stressors. 

PMID- 25983131
TI  - Acute meningoencephalitis associated with echovirus 9 infection in Sri Lanka,
      2009.
AB  - The aetiology of acute meningoencephalitis in Sri Lankan children and adults is
      poorly understood. This study was carried out to determine pathogens responsible
      for meningoencephalitis in Sri Lanka. A hospital-based cross-sectional study was
      performed using cerebrospinal fluid samples (22 adult and 17 pediatric) collected
      from August to December 2009 from patients clinically diagnosed with acute
      meningoencephalitis at two tertiary care hospitals in Sri Lanka. Routine
      microbiology for bacterial pathogens together with in-house RT-PCR and PCR assays
      for the detection of dengue viruses, Japanese encephalitis virus, West Nile
      virus, chikungunya virus, enteroviruses, mumps virus, measles virus, herpes
      simplex viruses types 1 and 2, and varicella zoster virus were performed.
      Bacterial pathogens were not isolated from any patient specimens. However, from
      nine of the paediatric patients aged 1 month to 10 years (mean age 5.2 years)
      echovirus 9 (E-9; family Picornaviridae, genus Enterovirus,species Enterovirus B
      ) was detected by RT-PCR. All nine patients presented with fever, six had
      headache, and seven had vomiting. Neck stiffness indicating meningitis was
      present in six of the patients. Phylogenetic analysis of partial VP1 and VP4-VP2
      genes showed these E-9 strains to be most closely related to E-9 strains detected
      in CSF from Korea and France in 2005 and 2006. The remaining patients were
      negative for all other viruses tested. E-9 was the most common cause of acute
      meningoencephalitis in the tested paediatric population from Sri Lanka in 2009,
      which likely reflects circulation of this E-9 strain between Europe and Asia over
      several years.

PMID- 25983130
TI  - Secretome protein signature of human gastrointestinal stromal tumor cells.
AB  - Strategies for correct diagnosis, treatment evaluation and recurrence prediction
      are important for the prognosis and mortality rates among cancer patients. In
      spite of major improvements in clinical management, gastrointestinal stromal
      tumors (GISTs) can still be deadly due to metastasis and recurrences, which
      confirms the unmet need of reliable follow-up modalities. Tumor-specific
      secreted, shed or leaked proteins (collectively known as secretome) are
      considered promising sources for biomarkers, and suitable for detection in
      biofluids. Herein, we stimulated cell secretion in the imatinib-sensitive GIST882
      cell line and profiled the secretome, collected as conditioned media, by using a
      shotgun proteomics approach. We identified 764 proteins from all conditions
      combined, 51.3% being predicted as classically/non-classically secreted. The
      protein subsets found were dependent on the stimulatory condition. The
      significant increase in protein release by the classical pathway was strongly
      associated with markers already found in other cancer types. Furthermore, most of
      the released proteins were non-classically released and overlapped to a high
      degree with proteins of exosomal origin. Imatinib pre-treatment radically changed
      these secretory patterns, which can have clinical implications when investigating
      biomarkers in imatinib-treated versus non-treated GIST patients. Our results
      show, for the first time, that GISTs contain a secretome signature. In the search
      for suitable biomarkers in the more complex GIST patient samples, this study aids
      in the understanding of basic GIST secretome characteristics. 

PMID- 25983132
TI  - Various effects of fluorescent bacteria of the genus Pseudomonas containing ACC
      deaminase on wheat seedling growth.
AB  - The study evaluates the effect of rhizobacteria having 1-aminocyclopropane-1
      carboxylate deaminase (ACCd) on the development of wheat seedlings. This enzyme
      has been proposed to play a key role in microbe-plant association. Three
      fluorescent pseudomonads containing this deaminase were selected from 70 strains
      of pseudomonads isolated from rhizosphere of wheat (Triticum aestivum L.) and
      rape (Brassica napus L.). These bacteria, varied significantly in the ability to
      both biosynthesize auxins and hydrolyze ACC. Among them, Pseudomonas
      brassicacearum subsp. brassicacearum strain RZ310 presented the highest
      activities of ACC deaminase during 96h of growth in liquid Dworkin and Foster
      (DF) salt medium. Additionally, this rape rhizosphere strain did not produce
      indoles. Two other isolates, Pseudomonas sp. PO283 and Pseudomonas sp. PO366,
      secreted auxins only in the presence of their precursor. Phylogenetic analysis of
      the 16S rRNA gene and four other protein-encoding genes indicated that these
      wheat rhizosphere isolates belonged to the fluorescent Pseudomonas group.
      Moreover, the effects of these strains on wheat seedling growth under in vitro
      conditions were markedly dependent on both their cell suspensions used to grain
      inoculation and nutrient conditions. Strains tested had beneficial influence on
      wheat seedlings mainly at low cell densities. In addition, access to nutrients
      markedly changed bacteria action on cereal growth. Their presence generally
      favored the positive effects of pseudomonads on length and the estimated
      biomasses of wheat coleoptiles. Despite these general rules, impacts of each
      isolate on the growth parameters of cereal seedlings were unique. 

PMID- 25983133
TI  - Automatic evidence quality prediction to support evidence-based decision making.
AB  - BACKGROUND: Evidence-based medicine practice requires practitioners to obtain the
      best available medical evidence, and appraise the quality of the evidence when
      making clinical decisions. Primarily due to the plethora of electronically
      available data from the medical literature, the manual appraisal of the quality
      of evidence is a time-consuming process. We present a fully automatic approach
      for predicting the quality of medical evidence in order to aid practitioners at
      point-of-care. METHODS: Our approach extracts relevant information from medical
      article abstracts and utilises data from a specialised corpus to apply supervised
      machine learning for the prediction of the quality grades. Following an in-depth
      analysis of the usefulness of features (e.g., publication types of articles),
      they are extracted from the text via rule-based approaches and from the meta-data
      associated with the articles, and then applied in the supervised classification
      model. We propose the use of a highly scalable and portable approach using a
      sequence of high precision classifiers, and introduce a simple evaluation metric
      called average error distance (AED) that simplifies the comparison of systems. We
      also perform elaborate human evaluations to compare the performance of our system
      against human judgments. RESULTS: We test and evaluate our approaches on a
      publicly available, specialised, annotated corpus containing 1132 evidence-based
      recommendations. Our rule-based approach performs exceptionally well at the
      automatic extraction of publication types of articles, with F-scores of up to
      0.99 for high-quality publication types. For evidence quality classification, our
      approach obtains an accuracy of 63.84% and an AED of 0.271. The human evaluations
      show that the performance of our system, in terms of AED and accuracy, is
      comparable to the performance of humans on the same data. CONCLUSIONS: The
      experiments suggest that our structured text classification framework achieves
      evaluation results comparable to those of human performance. Our overall
      classification approach and evaluation technique are also highly portable and can
      be used for various evidence grading scales.

PMID- 25983134
TI  - Differential expression of extracellular thiol groups of moderately thermophilic
      Sulfobacillus thermosulfidooxidans and extremely thermophilic Acidianus
      manzaensis grown on S(0) and Fe (2.).
AB  - Bio-oxidation of elemental sulfur (S(0)) is very important in bioleaching and
      sulfur cycle. S(0) was proposed to be first activated by reacting with reactive
      thiol groups (-SH) of outer membrane proteins, forming -S n H (n >= 2) complexes.
      The differential expression of -SH of moderately thermophilic Sulfobacillus
      thermosulfidooxidans and extremely thermophilic Acidianus manzaensis grown on
      Fe(2+) and S(0) was investigated by synchrotron radiation-based scanning
      transmission X-ray microscopy (STXM) imaging and micro-beam X-ray fluorescence
      (MU-XRF) mapping. The STXM imaging and MU-XRF mapping of extracellular -SH were
      based on the analysis of Ca(2+) bound on the cell. By comparing Ca(2+) of the
      cells with and without labeling by Ca(2+), the distribution and content of thiol
      groups were obtained. The results showed that, for both S. thermosulfidooxidans
      and A. manzaensis, the expression of extracellular -SH of S(0)-grown cells was
      higher than that of Fe(2+)-grown cells. Statistical analysis indicated that the
      expression of extracellular -SH for S. thermosulfidooxidans and A. manzaensis
      grown on S(0) was 2.37 times and 2.14 times, respectively, to that on Fe(2+).
      These results evidently demonstrate that the extracellular thiol groups are most
      probably involved in elemental sulfur activation and oxidation of the acidophilic
      sulfur-oxidizing microorganisms. 

PMID- 25983135
TI  - Cell damage detection using Escherichia coli reporter plasmids: fluorescent and
      colorimetric assays.
AB  - Bacterial reporter assays are powerful tools used to study the effect of
      different compounds that affect the physiology of cellular processes. Most
      bacterial reporters are luciferase based and can be monitored in real time. In
      the present study we designed and implemented two sets of Escherichia coli
      bacterial reporter assays, using a multicopy plasmid system. Each reporter strain
      was constructed using either green fluorescent protein or beta-galactosidase
      (LacZ) proteins. The designed reporter strains are capable of responding in a
      specific manner to molecules that either oxidative stress, or membrane, protein,
      or DNA damage. In order to respond to the desired stimulus, promoter sequences
      from E. coli were used. These sequences correspond to the promoter of the major
      catalase (KatG) activated with cellular oxidative damage, the promoter of the
      beta-hydroxydecanoyl-ACP dehydrase (FabA) which is activated with membrane
      perturbation, the promoter of DNA recombinase (RecA) which is activated by DNA
      lesions. For protein misfolding, the promoter of the heat-shock responsive
      chaperon (DnaK) was used. Our constructs displayed activation to damage from
      specific stimuli, and low response to nonspecific stimuli was detected. Our
      results suggest that these types of bacterial reporter strains can be used in
      semiquantitative (fluorometric) and qualitative (beta-galactosidase activity)
      studies of different xenobiotic substances and pollutants. 

PMID- 25983136
TI  - Carotid bypass for carotid occlusion.
AB  - The 2-year risk of ipsilateral ischemic stroke following internal carotid artery
      occlusion (ICAO) in a patient undergoing maximal medical therapy is 5-8% per
      year. While medical therapy may reduce the risk of stroke, it does not completely
      eliminate it. Since the 1985 extracranial-intracranial (EC-IC) bypass study,
      additional trials have been conducted to further investigate the usefulness of EC
      IC bypass surgery in more selected patients with cerebral ischemia and impaired
      hemodynamic reserve. These important studies will be briefly reviewed in this
      article, as well as a discussion regarding the utility of bypass surgery for ICAO
      in current clinical practice. In addition, a short discussion regarding the
      pathophysiology of carotid occlusion will be presented. We will also highlight
      our own institutional patient selection criteria based on the latest methods for
      hemodynamic assessment, as well as our intraoperative flow assisted surgical
      techniques (FAST), and post-operative patient follow-up.

PMID- 25983137
TI  - Maternal and feto-placental phenotypes of early-onset severe preeclampsia.
AB  - OBJECTIVE: To characterize maternal and feto-placental phenotypes of severe
      preeclampsia that trigger early-onset delivery. METHODS: A retrospective cohort
      review of pregnant women receiving care from 2000 to 2010. Subjects with early
      onset severe preeclampsia delivering between 20 and 32 weeks were identified
      excluding multiple gestations or major anomalies. We defined indications for
      delivery as maternal (i.e. severe headache or abnormal laboratory parameters),
      feto-placental (i.e. non-reassuring tracing) or mixed (i.e. both maternal and
      feto-placental factors). To characterize the groups, demographic, clinical,
      laboratory, ultrasound and pathology data were abstracted. Statistical analysis
      was conducted. RESULTS: We identified 164 subjects meeting inclusion criteria.
      Indications for delivery were maternal (57.3%), feto-placental (29.9%) or mixed
      (12.8%). Compared to neonates delivered for maternal indications, birthweight was
      significantly lower among neonates delivered for feto-placental or mixed
      indications (p < 0.001). While placental findings were largely similar between
      groups, abnormal cord insertion was more common in subjects delivered for feto
      placental factors (p = 0.02). Women delivered for maternal indications had more
      significant lab abnormalities than women delivered for feto-placental or mixed
      indications. CONCLUSION: In attempting to classify early-onset severe
      preeclampsia by delivery indication, we found patterns to suggest that feto
      placental and maternal phenotypes of disease may have distinct pathophysiologic
      underpinnings.

PMID- 25983138
TI  - Relationship between interpregnancy interval and cervical length in high-risk
      women.
AB  - OBJECTIVE: Our objective was to evaluate the relationship between the
      interpregnancy interval (IPI) and next-pregnancy mid-trimester cervical length
      (CL) in women at high risk for recurrent spontaneous preterm birth (SPTB).
      METHODS: Retrospective review identified high-risk women, defined as a prior SPTB
      <36 weeks, who began scheduled serial transvaginal sonographic CL screening at 16
      18 weeks gestation between December 2008 and November 2010. All CL assessment
      ended by 22(6/7) weeks, and weekly 17-alpha hydroxyprogesterone caproate, 250 mg
      IM, was recommended to all patients. Details of the prior and current pregnancy
      were collected, and regression models were used to evaluate the relationship
      between IPI and CL shortening. RESULTS: One hundred and eight women with
      singleton gestations and a qualifying SPTB underwent CL screening. The mean (SD)
      birth gestational age (GA) of the last pregnancy was 25 (10) weeks, the median
      IPI was 613 (range 49-6038) days, and the mean (SD) delivery GA in the current
      pregnancy was 36 (5.3) weeks. Linear regression found no significant relationship
      between the IPI and the GA of the current birth (p = 0.98). There was a weak
      significant relationship between IPI and shortest CL (p = 0.04). However, after
      controlling for the GA of the prior pregnancy, this relationship was non
      significant (p = 0.13). CONCLUSIONS: IPI does not predict next birth outcome or
      next-pregnancy mid-trimester CL in high-risk women managed with progesterone and
      ultrasound-indicated cerclage.

PMID- 25983139
TI  - Age might confound the impact of the transmembrane 6 superfamily member 2 E167K
      polymorphism on hepatic fibrosis in hepatitis C virus-infected patients.

PMID- 25983140
TI  - Classic crush and DK crush stenting techniques.
AB  - Clinical data have supported the advantages of the double kissing (DK) crush
      technique, which consists of stenting the side branch (SB), balloon crush, first
      kissing, stenting the main vessel (MV) and final kissing balloon inflation, for
      complex coronary bifurcation lesions compared to other stenting techniques.
      Careful rewiring from the proximal cell of the MV stent to make sure the wire is
      in the true lumen of the SB stent is key to acquiring optimal angiographic
      results. Balloon anchoring from the MV, alternative inflation and each kissing
      inflation using large enough non-compliant balloons at high pressure, and the
      proximal optimisation technique are mandatory to improve both angiographic and
      clinical outcomes. Stratification of a given bifurcation lesion is recommended
      before decision making.

PMID- 25983141
TI  - Differences between the left main and other bifurcations.
AB  - The left main is the largest bifurcation of the coronary tree and is, therefore,
      easier to access. Nevertheless, the risks of untoward consequences associated
      with the loss of the side branch are much higher. Although the usual technical
      strategies implemented in coronary bifurcations can generally be applied to left
      main lesions, several inherent characteristics (the ostial position of the main
      branch, the size of the side branch, the amount of calcification, the angle which
      is often in a T shape, the use of stents of variable suitability, the crucial
      role of POT) need to be taken into account in order to achieve optimal acute and
      long-term results. 

PMID- 25983142
TI  - CABG, stents, or hybrid procedures for left main disease?
AB  - Coronary artery bypass graft (CABG) surgery, including grafting of the left
      internal mammary artery (LIMA) to the left anterior descending artery (LAD) with
      additional vein or IMA grafts to other vessels, remains the standard technique
      for treatment of three-vessel coronary artery disease in patients with an
      intermediate or high SYNTAX score. Unprotected left main coronary disease is most
      often found in association with multivessel disease. In these patients, CABG has
      long been considered the gold standard for revascularisation. However, the
      evidence is being challenged by technological and procedural advances in
      percutaneous coronary intervention. Especially in patients with low to
      intermediate anatomic complexity of left main disease, PCI can be an effective
      and durable treatment option. Left main bifurcation lesions, however, remain a
      challenging subset for PCI due to possible plaque shift and occlusion of a major
      side branch. While there is general agreement that coronary bypass
      revascularisation using the LIMA to the LAD provides the best long-term
      prognostic benefit, a combination of CABG to the LAD and PCI of the remaining
      lesions, a hybrid approach, takes advantage of the survival benefit of the LIMA
      to LAD bypass, while minimising invasiveness and lowering morbidity by avoiding
      median sternotomy, rib retraction, aortic manipulation, and cardiopulmonary
      bypass. In particular, elderly patients with severe concomitant diseases may
      benefit from this approach by avoiding CPB. 

PMID- 25983143
TI  - The EXCEL and NOBLE trials: similarities, contrasts and future perspectives for
      left main revascularisation.
AB  - Unprotected left main coronary artery (ULMCA) stenosis has relatively high
      prevalence and exposes patients to a high risk for adverse cardiovascular events.
      The optimal revascularisation strategy (coronary artery bypass surgery [CABG] or
      percutaneous coronary intervention [PCI]) for patients with complex coronary
      artery disease is a topic of continuing debate. The introduction of the newer
      generation drug-eluting stents (DES) -with documented improvements in both safety
      and efficacy- has prompted the interventional community to design two new
      dedicated randomised trials comparing CABG and PCI: the NOBLE (Coronary Artery
      Bypass Grafting Vs Drug Eluting Stent Percutaneous Coronary Angioplasty in the
      Treatment of Unprotected Left Main Stenosis) and EXCEL (Evaluation of XIENCE
      Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness
      of Left Main Revascularization) trials. The aims of the present review are to
      describe the similarities and contrasts between these two trials as well to
      explore their future implications in ULMCA treatment. 

PMID- 25983144
TI  - When and how to perform the provisional approach for distal LM stenting.
AB  - Despite the tremendous developments that have been made in the field of
      interventional cardiology over the past few decades, the percutaneous treatment
      of left main (LM) bifurcation still remains challenging. The provisional one
      stent approach for LM bifurcation showed more favourable outcomes compared to the
      double-stenting technique. Consequently, it has been the preferred strategy in
      the majority of LM bifurcation stenosis. However, due to the large myocardial
      burden of the side branch, the risk of haemodynamic collapse after main vessel
      stenting has always existed. To reduce the risk of side branch occlusion and for
      proper selection of this strategy, it is acknowledged that meticulously performed
      IVUS evaluation of the side branch ostium is helpful. A fractional flow reserve
      measurement of the angiographically jailed side branch could also lead to the
      avoidance of an unnecessary complex intervention. However, as the overall data
      were derived from observational studies, further larger randomised trials would
      be necessary to assess the optimal provisional one-stent strategy for LM
      bifurcation. 

PMID- 25983145
TI  - Which technique for double stenting in unprotected left main bifurcation coronary
      lesions?
AB  - Unprotected left main (LM) bifurcation coronary lesions are challenging for
      interventionists because these lesions are associated with relatively poor
      outcomes after percutaneous coronary intervention (PCI). Although the single
      stent technique is a default treatment strategy for LM bifurcation lesions,
      elective double stenting is still used in patients with severely diseased side
      branches. The crush technique and its variants, the culotte technique and the
      simultaneous kissing stent technique, are applicable for distal LM disease, but
      none of these has proven to be superior to the others. Good long-term clinical
      outcomes are closely related to procedural success and optimisation of the
      stenting technique. The use of kissing balloon inflation during any double-stent
      technique is known to be an independent predictor of good angiographic and
      clinical outcomes by avoiding incomplete apposition or expansion. Moreover,
      procedural guidance using intravascular ultrasound may improve outcomes by
      helping to determine the appropriate stenting technique and optimise the stent
      procedure. Therefore, more attention should be paid to optimising the chosen
      technique than to choosing among techniques. 

PMID- 25983146
TI  - Dedicated stents for distal left main stenting.
AB  - Left main (LM) coronary bifurcation lesions have different anatomic features from
      non-LM bifurcation lesions. Dedicated bifurcation devices might facilitate
      percutaneous coronary intervention (PCI) of LM bifurcations and improve
      procedural and clinical outcomes. In this review we will discuss the available
      clinical data on dedicated bifurcation devices for the treatment of LM
      bifurcation lesions. Furthermore, we will try to discuss all the theoretical
      advantages and potential drawbacks of these devices in terms of their use in the
      LM. 

PMID- 25983147
TI  - Anatomy and function relation in the coronary tree: from bifurcations to
      myocardial flow and mass.
AB  - The study of the structure-function relation of coronary bifurcations is
      necessary not only to understand the design of the vasculature but also to use
      this understanding to restore structure and hence function. The objective of this
      review is to provide quantitative relations between bifurcation anatomy or
      geometry, flow distribution in the bifurcation and degree of perfused myocardial
      mass in order to establish practical rules to guide optimal treatment of
      bifurcations including side branches (SB). We use the scaling law between flow
      and diameter, conservation of mass and the scaling law between myocardial mass
      and diameter to provide geometric relations between the segment diameters of a
      bifurcation, flow fraction distribution in the SB, and the percentage of
      myocardial mass perfused by the SB. We demonstrate that the assessment of the
      functional significance of an SB for intervention should not only be based on the
      diameter of the SB but also on the diameter of the mother vessel as well as the
      diameter of the proximal main artery, as these dictate the flow fraction
      distribution and perfused myocardial mass, respectively. The geometric and flow
      rules for a bifurcation are extended to a trifurcation to ensure optimal therapy
      scaling rules for any branching pattern. 

PMID- 25983148
TI  - Bioresorbable vascular scaffolds in left main coronary artery disease.
AB  - Currently, the use of bioresorbable vascular scaffolds (BRS) for the treatment of
      left main (LM) coronary artery disease has to be considered investigational.
      However, some early evidence from case reports supports the feasibility of BRS
      implantation in selected cases and shows good angiographic and clinical results
      with current-generation BRS devices. However, before the routine use of BRS for
      LM disease can be advocated, more data on long-term safety and efficacy and
      larger scaffold designs are essential. 

PMID- 25983149
TI  - Is there a need for dedicated devices?
AB  - Although the provisional approach is recommended over a systematic two-stent
      approach in bifurcation lesions, an a priori two-stent approach may be considered
      in certain specific anatomies in a minority of cases. Virtual bench test and
      intravascular imaging studies have provided essential insights into the technical
      aspects of bifurcation stenting and led to recommendations on how to optimise
      both the provisional and the two-stent strategies. Dedicated bifurcation stents
      may further optimise the procedural and clinical outcomes of both strategies.
      However, randomised data are sparse and more randomised trials are needed to
      provide evidence as to whether these dedicated devices will indeed improve
      procedural and clinical outcomes. 

PMID- 25983150
TI  - The Axxess stent.

PMID- 25983151
TI  - The Tryton Side Branch Stent.

PMID- 25983152
TI  - The STENTYS Self-Apposing(r) stent.

PMID- 25983153
TI  - The Nile CroCo and Nile PAX stents.

PMID- 25983154
TI  - The ABS mother-daughter platforms.

PMID- 25983155
TI  - The BiOSS stent.

PMID- 25983156
TI  - Technology limitations of BRS in bifurcations.
AB  - Recommended techniques for bifurcation stenting continue to be revised with
      specific attention to bioresorbable scaffolds (BRS). Optimal procedural success
      and long-term outcomes with BRS can perhaps be improved with careful attention to
      implantation techniques. Good vessel preparation is imperative for optimal
      expansion of the scaffold, and proper vessel sizing is necessary to ensure
      compliance with scaffold expansion limits and preservation of proper scaffold
      function. The European Bifurcation Club (EBC) recommends provisional stenting for
      the majority of bifurcation lesions: permanent metallic stents are sized
      according to the distal vessel diameter, with subsequent post-dilatation of the
      proximal vessel to ensure stent apposition in the proximal main vessel. Recent
      BRS-specific modifications to the EBC recommendation suggest that selecting the
      scaffold size based on the diameter of the proximal main vessel can mitigate the
      risk of overexpansion and potential strut fracture. Expansion of the BRS requires
      a thoughtful balance between the risk of malapposition associated with
      underdeployment and the risk of strut fracture due to overdeployment. Post
      dilatation of scaffolds should be performed, always respecting the maximum
      expansion limit, to correct any potential scaffold malapposition and minimise
      flow disturbances. Finally, dual antiplatelet therapy plays an important role in
      BRS bifurcation treatment to avoid thromboembolic events. 

PMID- 25983157
TI  - Pathological aspects of bioresorbable stent implantation.
AB  - The treatment of obstructive coronary artery disease has been revolutionised by
      the advent of drug-eluting stent therapy. However, concerns remain about
      complications late after stent implantation including late stent thrombosis,
      hypersensitivity reactions and neoatherosclerosis. In this respect, the
      introduction of fully bioresorbable stents (BRS)--which resorb over time and
      leave the arterial wall free of any metal constraints--represents a potentially
      important disruptive technology. However, although the concept is intuitively
      attractive, a thorough understanding of the histopathological changes seen after
      BRS implantation and an appreciation of comparative changes versus existing metal
      stent technologies are vital to guide BRS clinical usage. In this respect,
      translational investigation of polymer chemistry, biomedical engineering, as well
      as in vitro and in vivo testing in animal models is an important undertaking.
      This article will review the pathological aspects of BRS implantation with a
      focus on acute and chronic vascular reactions derived from preclinical animal
      studies, including insights from in vivo imaging. Finally, potential future
      directions of this novel therapeutic approach will be discussed.

PMID- 25983158
TI  - Bioresorbable scaffolds on the bench.
AB  - Bioresorbable scaffolds (BRS) in bifurcations have all of the potential
      advantages of BRS in non-bifurcating lesions and, in addition, the absorption of
      side branch (SB) ostial struts may at least partially release the branch from
      "jail". Polymeric BRS struts may break when post-dilated beyond their safe limits
      and multiple fractures may lead to adverse clinical events. Bench testing
      provides insights into the behaviour of different BRS in bifurcations and helps
      the interventional cardiologist to choose, deliver and post-dilate appropriately.
      Bench testing of polymeric BRS must be in a water bath at 37oC as polymer
      performance is temperature sensitive. Balloon dilatation through the side of a
      BRS or a durable metallic stent causes distortion corrected by mini-kissing
      balloon post-dilatation (mini-KBPD) where the SB balloon extends only a short
      distance into the main branch (MB), limiting the length of MB scaffold exposed to
      the inflation of two balloons. The safe pressure threshold for SB dilatation of a
      3.0 mm Absorb scaffold with a 3.0 mm non-compliant balloon is 10 atm and for mini
      KBPD with two 3.0 mm balloons it is 5 atm. Strategies such as culotte, crush and
      simultaneous kissing scaffolds (SKS) may not be appropriate for the current
      Absorb scaffold. 

PMID- 25983159
TI  - Lessons from the GHOST-EU registry.
AB  - Bifurcations are increasingly being treated with bioresorbable vascular scaffolds
      (BVS) and accounted for about 25% of patients treated in the large multicentre
      GHOST-EU registry. This registry, along with bench testing, has provided a
      glimpse of the techniques and limitations of treating bifurcations with BVS. The
      provisional strategy remains the default approach to bifurcation treatment with
      BVS. If correctly performed, SB dilatation, T-kissing inflation, crossover to
      side branch stenting and elective double stenting are feasible without causing
      scaffold disruption. Theoretically, when the scaffolds are resorbed, the normal
      bifurcation anatomy, flow and vascular function will be restored, while jailed
      SBs will be liberated. However, data from the GHOST-EU registry are awaited to
      confirm the long-term safety and efficacy of BVS in coronary bifurcations. 

PMID- 25983160
TI  - Treatment of bioresorbable scaffold failure.
AB  - Bioresorbable scaffolds (BRS) are a promising new interventional treatment
      strategy for coronary artery disease (CAD). They are intended to overcome some of
      the shortcomings of metal drug-eluting stents (DES), mainly late reinterventions
      which occur at a consistent rate after one year and have not been reduced by the
      use of local drug elution. Initial experience in non-complex lesions established
      efficacy in opening the vessel and the concept of bioresorption. However, with
      the use of BRS in more complex lesions, the incidence of BRS failure, including
      both scaffold restenosis and thrombosis, has also increased. Therefore,
      understanding of both the pathophysiology and of the available treatment options
      of scaffold failure remains an important issue in ensuring procedural and long
      term clinical success. 

PMID- 25983161
TI  - Impact of local flow haemodynamics on atherosclerosis in coronary artery
      bifurcations.
AB  - Coronary artery bifurcations are susceptible to atherosclerosis as a result of
      the unique local flow patterns and the subsequent endothelial shear stress (ESS)
      environment that are conducive to the development of plaques. Along the lateral
      walls of the main vessel and side branches, a distinct flow pattern is observed
      with local low and oscillatory ESS, while high ESS develops at the flow divider
      (carina). Histopathologic studies have shown that the distribution of plaque at
      bifurcation regions is related to the local ESS patterns. The local ESS profile
      also influences the outcome of percutaneous coronary interventions in bifurcation
      lesions. A variety of invasive and non-invasive imaging modalities have enabled
      3D reconstruction of coronary bifurcations and thereby detailed local ESS
      assessment by computational fluid dynamics. Highly effective strategies for
      treatment and ultimately prevention of atherosclerosis in coronary bifurcations
      are anticipated with the use of advanced imaging and computational fluid dynamic
      techniques. 

PMID- 25983162
TI  - What about the risk of thrombosis with bioresorbable scaffolds?
AB  - Bioresorbable scaffolds promise to counteract late thrombosis by the absence of
      residual foreign material over time and the restoration of functional endothelial
      coverage. However, although currently available data are controversial, initial
      post-marketing studies have raised some concerns about the putative increased
      early thrombogenicity of bioresorbable scaffolds as compared to currently
      available second-generation drug-eluting stents. This article focuses on
      incidence rates, putative mechanisms and prevention strategies of scaffold
      thrombosis. 

PMID- 25983163
TI  - When and how to use BRS in bifurcations?
AB  - Bioresorbable coronary scaffolds (BRS) may offer potential advantages compared to
      metallic DES, aiming to restore vessel patency without implanting a permanent
      prosthesis, which may be especially important for bifurcation treatment. On the
      other hand, there are some inherent limitations, which may impact on the
      widespread use of BRS. In the current article we discuss the bench testing data
      and initial clinical results on BRS use in bifurcation lesions presented during
      European Bifurcation Club (EBC) meetings and review some of the limited number of
      published real-world registry results. 

PMID- 25983164
TI  - The future of BRS in bifurcations.
AB  - Bioresorbable scaffolds (BRS) provide a new tool for percutaneous treatment of
      coronary stenosis. Initially, relatively simple coronary artery lesions were
      treated with this novel technology; nowadays, we have gained more experience with
      a wide variety of lesions, including bifurcation lesions. Data are limited in
      terms of the use of BRS in coronary bifurcation lesions, although it has been
      demonstrated that over time the bioresorbable struts are replaced by a tissue
      bridge resembling a "neo-carina". Furthermore, data are emerging about the
      endothelial shear stress (ESS) alterations and blood flow patterns after scaffold
      implantation. It is likely that ESS and blood flow determinations will guide
      correct future bifurcation techniques. In the future, BRS with thinner struts and
      more resistant to fracture are likely to improve bifurcation treatment with BRS. 

PMID- 25983165
TI  - Definitions and classifications of bifurcation lesions and treatment.
AB  - This article introduces the new terminology proposed by the European Bifurcation
      Club in order to simplify the identification, description, localisation and
      measurement of coronary bifurcation lesions as well as the selection of
      appropriate treatment strategies. A bifurcation lesion is a coronary artery
      narrowing occurring adjacent to, and/or involving, the origin of a significant
      side branch that you do not want to lose. The very simple Medina classification
      is intended for exchange and clinical research purposes. It is combined with a
      clear side branch definition and is associated with multiple measurement and
      imaging modalities, which take into account the complexity of lesions and
      treatments. Dedicated angiography as well as 3D angiography and multislice
      computed tomography are absolutely necessary for measurement of the bifurcation
      angles. The MADS (Main, Across, Distal, Side) classification is based on the
      final position of the stents in the bifurcation and on the order in which stents
      are implanted according to a strategy reflecting lesion and technique complexity.
      Although this classification still seems exhaustive, it does not involve the
      numerous guide and balloon manoeuvres, which would require a thorough a
      posteriori electronic classification of all inherent specific technical details. 

PMID- 25983166
TI  - Lessons from the real bench: non-BRS.
AB  - Bench testing of stents used in bifurcations can provide information on the
      general properties that influence performance including crossing profile, radial
      strength, recoil, flexibility and radiopacity. Problems with device delivery can
      be clarified. Bench testing identified that side branch dilatation caused stent
      distortion and elucidated correction strategies. Bench testing led to a stent
      design change adding connectors between hoops to help overcome the clinical
      problem of longitudinal distortion. Testing on the bench can determine best
      deployment strategies and showed that a two-step post-dilatation strategy
      produced the best deployment with "crush" stenting. Scanning electron microscopy
      showed that withdrawal of a coronary guidewire trapped between a stent (or
      scaffold) and a mock arterial wall during a provisional side branch stenting
      strategy caused only mild linear polymer coating damage. Stent fracture can cause
      adverse clinical events and our repetitive bend test identified the stents most
      resistant to fracture. Causes of obstruction of the passage of a balloon over a
      wire through the side of a stent include damage to the catheter tip, complex cell
      geometry and inadvertent passage of a wire behind a strut. Bench testing plays a
      major role in validation of computer modelling of bifurcation treatments and flow
      alterations. 

PMID- 25983167
TI  - Virtual bench testing to study coronary bifurcation stenting.
AB  - Virtual bench testing is a numerical methodology which has been applied to the
      study of coronary interventions. It exploits the amazing growth of computer
      performance for scientific calculation and makes it possible to simulate very
      different and complex multiphysics environments and processes, including coronary
      bifurcation stenting. The quality of prediction from any computer model is very
      sensitive to the quality of the input data and assumptions. This also holds true
      in stent virtual bench testing. This paper reviews the state of the art in the
      field of bifurcation stenting modelling and identifies the current advantages and
      limitations of this methodology. 

PMID- 25983168
TI  - Patient-specific computer modelling of coronary bifurcation stenting: the John
      Doe programme.
AB  - John Doe, an 81-year-old patient with a significant distal left main (LM)
      stenosis, was treated using a provisional stenting approach. As part of an
      European Bifurcation Club (EBC) project, the complete stenting procedure was
      repeated using computational modelling. First, a tailored three-dimensional (3D)
      reconstruction of the bifurcation anatomy was created by fusion of multislice
      computed tomography (CT) imaging and intravascular ultrasound. Second, finite
      element analysis was employed to deploy and post-dilate the stent virtually
      within the generated patient-specific anatomical bifurcation model. Finally,
      blood flow was modelled using computational fluid dynamics. This proof-of-concept
      study demonstrated the feasibility of such patient-specific simulations for
      bifurcation stenting and has provided unique insights into the bifurcation
      anatomy, the technical aspects of LM bifurcation stenting, and the positive
      impact of adequate post-dilatation on blood flow patterns. Potential clinical
      applications such as virtual trials and preoperative planning seem feasible but
      require a thorough clinical validation of the predictive power of these computer
      simulations. 

PMID- 25983169
TI  - Coronary bifurcations as you have never seen them: the Visible Heart(r)
      Laboratory bifurcation programme.
AB  - The Visible Heart(r) Laboratory is an original experimental laboratory in which
      harvested animal hearts are resuscitated and connected to a support machine in
      order to beat outside the animal body. Resuscitated animal hearts may be exposed
      to various types of endovascular intervention under full, multimodality
      inspection. This unique experimental setting allows the performance of
      percutaneous coronary intervention (PCI) in a setting which resembles a standard
      catheterisation laboratory set-up, and contemporaneously allows unique
      multimodality imaging. For these reasons, the performance of PCI on bifurcations
      in the Visible Heart(r) Laboratory may improve the knowledge of the dynamic stent
      deformations and stent-vessel wall interactions associated with the different
      steps of the various techniques for bifurcation stenting. Furthermore, the
      collected images may also serve as a novel educative resource for physicians. The
      performance of bifurcation stenting in the Visible Heart(r) Laboratory is a
      promising experimental setting to gain novel information regarding any existing
      or future PCI technique to treat coronary bifurcations. 

PMID- 25983170
TI  - The need for dedicated bifurcation quantitative coronary angiography (QCA)
      software algorithms to evaluate bifurcation lesions.
AB  - Single-vessel quantitative coronary angiography (QCA) software is inaccurate when
      used in bifurcation lesions due to the specific anatomical characteristics of
      bifurcations, including the natural step-down in diameters after every
      bifurcation. Dedicated bifurcation QCA software has been developed to overcome
      the limitations of single-vessel QCA in bifurcations. A phantom validation study
      has shown the superior accuracy of these bifurcation QCA algorithms compared to
      the single-vessel QCA software. These QCA software algorithms are currently
      highly recommended to assess bifurcation lesions. 

PMID- 25983171
TI  - Image-based assessment of fractional flow reserve.
AB  - Pressure-derived fractional flow reserve (FFR) is an index of the haemodynamic
      significance of a coronary lesion. Numerous studies have provided robust evidence
      that FFR-guided percutaneous coronary intervention is associated with better
      clinical outcomes and reduces the need for repeat revascularisation. Although FFR
      is regarded as the gold standard for assessing lesion severity, it has limited
      clinical applications, mainly because it is a relatively expensive and time
      consuming procedure. To overcome these limitations, several computational-based
      methodologies have been developed which enable estimation of the FFR in three
      dimensional models derived from anatomic imaging data. Multislice computed
      tomographic coronary angiography and quantitative coronary angiography have been
      proposed for coronary reconstruction and computational evaluation of the FFR. In
      this review article, we describe the currently available methodologies for the
      computational estimation of FFR, present evidence derived from their clinical
      evaluations, stress their limitations, and discuss their potential value in
      clinical practice. 

PMID- 25983172
TI  - IVUS in bifurcation stenting: what have we learned?
AB  - Coronary angiography is unable to visualise the atherosclerotic involvement of
      the arterial wall. Bifurcation lesions are particularly difficult to assess by
      angiography because overlapping mother and daughter vessels often obscure the
      lesion and carina. On the contrary, IVUS imaging allows for precise, real-time,
      cross-sectional assessment of all bifurcation lesion segments, enabling
      measurements of luminal and vessel areas. Moreover, IVUS evaluation of stent
      expansion, apposition and edge problems is also superior to angiographic
      assessment. In spite of the lack of adequately powered randomised trials, there
      is growing evidence from large registries and meta-analyses showing better acute
      and long-term outcomes of DES implantation guided by IVUS, in comparison to
      angiography-guided procedures. In this review, we summarise current scientific
      evidence, the European Society of Cardiology recommendations and the European
      Bifurcation Club consensus for the use of IVUS in bifurcation stenting. 

PMID- 25983173
TI  - Coronary fractional flow reserve in bifurcation stenoses: what have we learned?
AB  - Fractional flow reserve (FFR) is a useful tool for the evaluation of coronary
      bifurcation lesions. FFR can guide treatment strategy, simplify the procedure and
      reduce unnecessary complex interventions. However, the application of FFR to
      complex bifurcation lesions requires a comprehensive understanding of its roles
      and potential pitfalls. Furthermore, FFR should be interpreted in the context of
      complex bifurcation anatomy and physiology rather than as a simple number.
      Finally, it should be recalled that the ischaemic burden is more important than
      the presence of ischaemia, and the risk/benefit of a complex intervention should
      be incorporated into the treatment decision after FFR measurement. 

PMID- 25983174
TI  - OCT for bifurcation stenting: what have we learned?
AB  - Treatment of bifurcation lesions by percutaneous coronary intervention (PCI)
      shows major variation in complexity. Intravascular optical coherence tomography
      (OCT) provides high-resolution images of the pathoanatomy, thrombus, wires and
      stent positions during the procedure. This information may prove crucial in
      optimising PCI results and clinical outcomes after complex bifurcation treatment.
      Mounting evidence confirms the feasibility of OCT in bifurcations, and specific
      steps where OCT may be advantageous in guiding bifurcation PCI have been
      identified. Awaiting major clinical outcome trials, OCT has already entered the
      European guidelines for myocardial revascularisation. This paper aims to provide
      an overview of the potential clinical use of OCT in bifurcations. 

PMID- 25983175
TI  - The treatment of coronary bifurcations: a true art form.

PMID- 25983176
TI  - New implication of three-dimensional optical coherence tomography in optimising
      bifurcation PCI.
AB  - With the advance of optical coherence tomography (OCT) technology, three
      dimensional (3D) reconstruction based on the optical coherence tomography has
      become feasible. In bifurcation lesions, 3D OCT may guide positioning of the wire
      through the appropriate (distal) cells. The early studies suggested that such a
      guidance strategy could reduce the incidence of malapposition in bifurcation
      lesions. The pre-installed "real-time" 3D OCT on the console will promote the
      utilisation of 3D assessment in bifurcation treatment and possibly establish the
      clinical benefit of such guidance in the near future when investigated in a
      prospective study. 

PMID- 25983177
TI  - The story of plaque shift and carina shift.
AB  - Side branch (SB) occlusion is one of the most serious complications of main
      vessel (MV) stenting. Although plaque shift has been considered the major
      mechanism of SB occlusion, recent studies have suggested carina shift to be the
      more important cause. Considering the recent pressure wire as well as
      intravascular ultrasonography studies, the relationship between carina shift and
      plaque shift in SB occlusion can be described as follows. The anatomical
      compromise of the SB after MV stenting is not as functionally significant as it
      appears, because it is mostly explained by carina shift, which is not the major
      cause of functional compromise. Superimposition of plaque shift over carina shift
      appears to be the mechanism of haemodynamically significant SB stenosis. Plaque
      is shifted mostly from the proximal MV, which explains why the plaque burden of
      the proximal MV is a significant risk factor of SB functional compromise or
      occlusion. 

PMID- 25983178
TI  - The story of side branch predilatation before provisional stenting.
AB  - Bifurcation lesions remain a therapeutic challenge and present an increased risk
      of complications. It also seems clear that the provisional stenting strategy,
      using only one drug-eluting stent in the main vessel (MV), is the first choice of
      treatment for most patients. However, provisional stenting is not a unitary
      approach, and diverse technical possibilities such as the use of final kissing
      balloon inflation, or the type of drug-eluting stent implanted at the MV may
      influence the outcome of the procedure. In the context of provisional stenting,
      predilation of the side branch (SB) before MV stent implantation is another
      manoeuvre which could facilitate the performance of this technique. However, SB
      predilation has generated many controversies and it has been discussed at length
      during several sessions of the European Bifurcation Club meetings. In this paper
      we analyse the advantages and disadvantages of side branch predilation as well as
      the most relevant articles dealing with this topic. We conclude that predilation
      of the SB is in many cases probably not needed, but may be considered in order to
      simplify the procedure. Predilation of the SB is recommended when SB compromise
      after MV stenting is highly anticipated, such as in long ostial SB lesions or
      heavily calcified lesions. 

PMID- 25983179
TI  - Final kissing balloon inflation: the whole story.
AB  - Final kissing balloon inflation (KBI) after provisional bifurcation stenting has
      failed to provide clear clinical benefit except for a decrease in side branch
      stenosis, while a significant reduction of major adverse cardiac events has been
      documented in two-stent deployment. The optimisation of KBI in terms of proximal
      optimisation technique, appropriate guidewire re-crossing, minimal balloon
      overlapping, and balloon size selection may overcome the drawbacks of
      conventional KBI by: 1) correcting the proximal malapposition expected from
      fractal geometry; 2) optimising side branch ostium strut opening while conserving
      a bifurcation area free of malapposition at both the carina and the side branch
      ostium; and 3) optimising the geometry, velocity fields and shear rate. 

PMID- 25983180
TI  - Technical aspects of the provisional side branch stenting strategy.
AB  - Provisional side branch (SB) stenting is the recommended treatment strategy in
      the vast majority of bifurcation lesions. Over the past 10 years, advances in
      fundamental knowledge have led to a better understanding and to improvements of
      this technical approach. This strategy has reached maturity, and long-term
      clinical results are now comparable to those of non-bifurcation lesions. This
      paper describes in detail simple rules and tips and tricks which may help
      physicians in daily practice to use provisional side branch (SB) stenting as the
      gold standard treatment for the majority of bifurcation lesions. 

PMID- 25983181
TI  - The EuroIntervention coronary bifurcation treatment supplement.

PMID- 25983182
TI  - Technical aspects of the T And small Protrusion (TAP) technique.
AB  - The T and small protrusion (TAP) technique is a modification of provisional T
      stenting aimed at optimising "bail-out" SB stent implantation in bifurcated
      coronary lesions treated using the "provisional" approach. The main strengths of
      the TAP stenting technique are: compatibility with 6 Fr guiding catheters, full
      coverage of the side branch ostium, and facilitation of final kissing balloon
      inflation. The main drawback of TAP is related to the creation of a single layer
      stent strut neocarina of variable length. In this paper, we review the technical
      aspects which should be considered in order to achieve TAP stenting successfully
      in the case of "bail-out" need for side branch stenting. Furthermore, we report
      the technical details which may help in the practice of TAP stenting in complex
      bifurcated lesions with the anticipated high probability of requiring double
      stenting. Although no large trial has investigated this technique, the clinical
      results reported so far look promising. 

PMID- 25983183
TI  - When is a two-stent technique needed and which technique should then be used for
      bifurcation coronary lesions?
AB  - Although the guidelines recommend the provisional one-stent technique as a
      default technique for bifurcation coronary lesions, there are cases of
      bifurcations with large side branches (SB), difficult access and with ostial and
      diffuse disease extending more than 5 mm into the SB, where a two-stent strategy
      might be the best treatment option. Due to the inherent advantages and
      disadvantages of each two-stent technique, an appropriate technique should be
      selected according to each patient's clinical condition, bifurcation morphology
      and the operator's experience. Good long-term prognosis is most likely ensured by
      successful performance of each procedural step during the initial stenting. 

PMID- 25983184
TI  - Technical aspects of the culotte technique.
AB  - The culotte technique provides near perfect coverage of the carina and side
      branch ostium at the expense of an excess of metal covering the proximal end. It
      can be used in almost all true bifurcation lesions, but should be avoided in
      bifurcations when there is a large mismatch between the proximal main branch and
      the side branch diameters. The main disadvantage of this technique is that
      rewiring of both branches through the stent struts is required, which can be
      difficult, technically demanding, and time-consuming. 

PMID- 25983185
TI  - Subretinal transplantation of retinal pigment epithelium overexpressing fibulin-5
      inhibits laser-induced choroidal neovascularization in rats.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      elderly. Choroidal neovascularization (CNV) is the abnormal angiogenesis that
      causes severe visual loss in AMD. Fibulin-5 (Fbln5), which functions as an
      angiogenesis inhibitor, plays an important role in the pathogenesis of AMD. Here,
      we investigated whether subretinal transplantation of Fbln5-overexpressing
      retinal pigment epithelial (RPE) cells can inhibit CNV in vivo. Adult Long-Evans
      rats were used in this study. CNV was induced by laser photocoagulation. One week
      after laser-induced CNV, RPE cells expressing pZlen-Fbln5-IRES-GFP or the control
      pZlen-IRES-GFP vectors were transplanted into the subretinal space of the right
      and left eyes, respectively. CNV was evaluated using fundus photography, fundus
      fluorescein angiography (FFA), and hematoxylin and eosin staining. We found that
      CNV occurred at 1 week after photocoagulation, reaching peak activity at 3 weeks
      and remaining at a high level at 4-5 weeks after photocoagulation. Transplanted
      RPE cells survived for at least 4 weeks and migrated toward the retina.
      Subretinal transplantation of Fbln5-overexpressing RPE cells resulted in a
      significant reduction in the total area of leakage and the number of leakage
      spots compared with transplantation of RPE cells expressing only green
      fluorescent protein. Our findings suggest that subretinal transplantation of
      Fbln5-overexpressing RPE cells inhibits laser-induced CNV in rats and thus
      represents a promising therapy for the treatment of AMD. 

PMID- 25983186
TI  - Expression of ionotropic glutamate receptors, AMPA, kainite and NMDA, in the
      pigeon retina.
AB  - Glutamate is an excitatory neurotransmitter in the vertebrate retina. A previous
      study found vesicular glutamate transporter 2 (vGluT2) mRNA in the pigeon retina,
      suggesting that bipolar and ganglion cells are glutamatergic. The present study
      examined the localization of ionotropic glutamate receptors to identify receptor
      cells in the pigeon retina using in situ hybridization histochemistry. Nine
      subunits of AMPA receptor (GluA1, GluA2, GluA3, and GluA4), kainate receptor
      (GluK1, GluK2, and GluK4), and NMDA receptor (GluN1 and GluN2A) were found to be
      expressed in the inner nuclear layer (INL) and ganglion cell layers. GluA1,
      GluA2, GluA3, and GluA4 were primarily expressed in the inner half of INL, and
      the signal intensity was strong for GluA2, GluA3, and GluA4. GluK1 was intensely
      expressed in the outer half of INL, whereas GluK2 and GluK4 were mainly localized
      in the inner half of INL. GluN1 and GluN2A were moderately expressed in the inner
      half of INL. Horizontal cells expressed GluA3 and GluA4, and ganglion cells
      expressed all subunits examined. These results suggest that the glutamatergic
      neurotransmission in the pigeon retina is similar to that in mammals. 

PMID- 25983187
TI  - The development and implementation of a brief intervention for medically admitted
      suicide attempt survivors.
AB  - OBJECTIVE: The current study endeavored to establish the feasibility and
      acceptability of a brief intervention for medically admitted suicide attempt
      survivors. METHOD: Fifty patients admitted to a Level 1 trauma center were
      recruited following a suicide attempt. The first 10 patients provided information
      on what constituted usual care, which in turn informed the creation of the
      intervention manual and research design. The next 10 patients informed refinement
      of the intervention and research procedures. The final 30 patients were
      randomized in a pre-post research design to receive the teachable moment brief
      intervention plus usual care or usual care only. Patients were assessed prior to
      randomization and 1 month later by blinded research assistants. Outcomes included
      patient satisfaction, readiness to change problematic behaviors, reasons for
      living, and suicidal ideation. RESULTS: Patients rated the brief intervention as
      "good" to "great" on all items related to client satisfaction. Significant group
      * time interactions were observed for readiness to change (beta=9.02, S.D.=3.73,
      P=.02) and reasons for living (beta=29.60, S.D.=10.22, P=.004), suggesting
      greater improvement for those patients who received the brief intervention.
      CONCLUSIONS: Patients admitted to an acute inpatient medical setting may benefit
      from a brief intervention that complements usual care by focusing specifically on
      the functional aspects of the suicide attempt in a collaborative, patient
      centered manner.

PMID- 25983189
TI  - MicroRNA transcriptome analysis identifies miR-365 as a novel negative regulator
      of cell proliferation in Zmpste24-deficient mouse embryonic fibroblasts.
AB  - Zmpste24 is a metalloproteinase responsible for the posttranslational processing
      and cleavage of prelamin A into mature laminA. Zmpste24(-/-) mice display a range
      of progeroid phenotypes overlapping with mice expressing progerin, an altered
      version of lamin A associated with Hutchinson-Gilford progeria syndrome (HGPS).
      Increasing evidence has demonstrated that miRNAs contribute to the regulation of
      normal aging process, but their roles in progeroid disorders remain poorly
      understood. Here we report the miRNA transcriptomes of mouse embryonic
      fibroblasts (MEFs) established from wild type (WT) and Zmpste24(-/-) progeroid
      mice using a massively parallel sequencing technology. With data from 19.5 *
      10(6) reads from WT MEFs and 16.5 * 10(6) reads from Zmpste24(-/-) MEFs, we
      discovered a total of 306 known miRNAs expressed in MEFs with a wide dynamic
      range of read counts ranging from 10 to over 1 million. A total of 8 miRNAs were
      found to be significantly down-regulated, with only 2 miRNAs upregulated, in
      Zmpste24(-/-) MEFs as compared to WT MEFs. Functional studies revealed that miR
      365, a significantly down-regulated miRNA in Zmpste24(-/-) MEFs, modulates
      cellular growth phenotypes in MEFs. Overexpression of miR-365 in Zmpste24(-/-)
      MEFs increased cellular proliferation and decreased the percentage of SA-beta-gal
      positive cells, while inhibition of miR-365 function led to an increase of SA
      beta-gal-positive cells in WT MEFs. Furthermore, we identified Rasd1, a member of
      the Ras superfamily of small GTPases, as a functional target of miR-365. While
      expression of miR-365 suppressed Rasd1 3' UTR luciferase-reporter activity, this
      effect was lost with mutations in the putative 3' UTR target-site. Consistently,
      expression levels of miR-365 were found to inversely correlate with endogenous
      Rasd1 levels. These findings suggest that miR-365 is down-regulated in Zmpste24(
      /-) MEFs and acts as a novel negative regulator of Rasd1. Our comprehensive miRNA
      data provide a resource to study gene regulatory networks in MEFs.

PMID- 25983190
TI  - Quantitative analysis of isomeric (l-alpha-, l-beta-, D-alpha-, D-beta-) aspartyl
      residues in proteins from elderly donors.
AB  - Homochirality is essential for life. For a long time, it was considered that d
      amino acids were excluded from living systems. In the past 30 years, however, d
      amino acids have been found in living organisms in the form of free amino acids,
      peptides and proteins, owing to advances in the analysis of optical isomers of
      amino acids. Free D-amino acids and D-amino-acid-containing peptides have been
      shown to have important physiological functions. The amount of D-aspartate (Asp)
      residues in protein spontaneously increases in metabolically inert tissues such
      as the eye and brain during aging, and may be related to cataract formation and
      the development of Alzheimer disease, suggesting that D-Asp might be a molecular
      marker of aging and age-related disorders. The presence of D-Asp in living
      organisms is thought to result from the isomerization of L-Asp residues in some
      proteins. Furthermore, the isomerization of Asp does not occur uniformly but only
      at specific sites. Therefore, it is necessary to determine the sites of isomeric
      Asp in these proteins in order to elucidate the mechanism of spontaneous Asp
      isomerization during aging. Herein, we summarize the localization and mechanism
      of D-amino acids in proteins of living tissues, and the effects of D-amino acid
      formation in proteins. Furthermore, we describe methods for the analysis of
      protein-bound D-amino acids including a conventional enantioseparation method
      based on HPLC and a new convenient method based on LC-MS that can identify the
      specific sites of D-Asp in proteins.

PMID- 25983188
TI  - Association of poor subjective sleep quality with suicidal ideation among
      pregnant Peruvian women.
AB  - OBJECTIVE: To examine the independent and joint relationships of poor subjective
      sleep quality and antepartum depression with suicidal ideation among pregnant
      women. METHODS: A cross-sectional study was conducted among 641 pregnant women
      attending prenatal care clinics in Lima, Peru. Antepartum depression and suicidal
      ideation were assessed using the Patient Health Questionnaire-9 scale. Antepartum
      subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index
      (PSQI). Logistic regression procedures were performed to estimate odds ratios
      (aOR) and 95% confidence intervals (95% CI) adjusted for confounders. RESULTS:
      Overall, the prevalence of suicidal ideation in this cohort was 16.8% and poor
      subjective sleep quality was more common among women endorsing suicidal ideation
      as compared to their counterparts who did not (47.2% vs. 24.8%, P<.001). After
      adjustment for confounders including maternal depression, poor subjective sleep
      quality (defined using the recommended criteria of PSQI global score of >5 vs.
      <=5) was associated with a 1.7-fold increased odds of suicidal ideation
      (aOR=1.67; 95% CI 1.02-2.71). When assessed as a continuous variable, each 1-unit
      increase in the global PSQI score resulted in an 18% increase in odds for
      suicidal ideation, even after adjusting for depression (aOR=1.18; 95% CI 1.08
      1.28). Women with both poor subjective sleep quality and depression had a 3.5
      fold increased odds of suicidal ideation (aOR=3.48; 95% CI 1.96-6.18) as compared
      with those who had neither risk factor. CONCLUSION: Poor subjective sleep quality
      was associated with increased odds of suicidal ideation. Replication of these
      findings may promote investments in studies designed to examine the efficacy of
      sleep-focused interventions to treat pregnant women with sleep disorders and
      suicidal ideation.

PMID- 25983192
TI  - [Multiple sclerosis and verbal episodic memory: Critical review of cognitive
      processes and their assessment].
AB  - Memory impairment, especially verbal episodic memory (VEM), represents a common
      ground for cognitive complaint in patients with multiple sclerosis (MS). Beyond
      the difficulty caused in daily life, these deficits may impact on occupational
      activities. Neuropsychological assessment of these patients has to include VEM
      tests, to describe the level of dysfunction of the different processes
      contributing to VEM and, if required, to guide adapted cognitive rehabilitation.
      The objective of the present paper is to propose a critique review of the
      literature on VEM abilities in MS. This review will present the conceptual
      references and the psychometric characteristics of the main VEM tests applied in
      MS (isolated tests or included within more general batteries developed
      specifically for MS). In a second phase, we propose an inventory of work on MS
      presented as a function of the cognitive processes involved. This approach
      provides an approach to the limitations of each conception and possible
      terminological ambiguities. Contributions to knowledge of MS memory impairments
      will be clarified, as well as the impact of the disease characteristics (MS
      forms, disease duration, EDSS). 

PMID- 25983191
TI  - Rising to the challenge of multiple Cryptococcus species and the diseases they
      cause.
AB  - Cryptococcus neoformans and Cryptococcus gattii are well-studied basidiomyceteous
      yeasts that are capable of causing disease in healthy and immunocompromised
      people. The Conference on Cryptococcus and Cryptococcosis (ICCC) is held every
      three years: the accompanying Special Issue stems from the 9th ICCC and covers a
      subset of the topics related to these fungi in detail. This conference started
      with a revised and reduced estimate of disease burden globally, in part due to
      improved treatment for HIV(+) people. However, mortality from cryptococcosis
      remains consistently high for those unfortunate to have limited access to
      therapies or without underlying immunodeficiencies. As such, there are yet still
      great distances to be covered to address antifungal drug availability, the need
      for new antifungal agents and the timing and doses of these agents in conjunction
      with antiviral therapy, underscoring the importance of continued research. A
      notable point from the 9th ICCC was the research addressing the variation in the
      pathogen and host populations. Analysis of cryptococcal strain variability,
      particularly at the molecular level, has resolved distinct lineages with the
      consequence of a taxonomic revision that divides C. neoformans and C. gattii into
      seven Cryptococcus species. Similarly, analysis of host factors in so called
      "immune-competent" individuals revealed previously unrecognized risk factors.
      Research on these species has established them as important model organisms to
      understand gene evolution and function in other fungi and eukaryotes. The stage
      is set for the refinement of research directions, leading ultimately to better
      treatment of this monophyletic clade of pathogens in the genus Cryptococcus. 

PMID- 25983193
TI  - Does Peak Inspiratory Pressure Increase in the Prone Position? An Analysis
      Related to Body Mass Index.
AB  - PURPOSE: Percutaneous nephrolithotomy is commonly performed with the patient
      prone. There is concern that the prone position, especially in obese patients,
      negatively affects ventilation due to the restriction of chest compliance and
      respiratory mechanics. We analyzed the change in airway resistance between supine
      and prone positioning of patients undergoing percutaneous nephrolithotomy.
      MATERIALS AND METHODS: We retrospectively reviewed the intraoperative respiratory
      parameters of 101 patients who underwent prone percutaneous nephrolithotomy. Peak
      inspiratory pressure was assessed with the patient supine, at several time points
      after being turned prone and at the end of the case. The change in peak
      inspiratory pressure with time was calculated. Results were stratified based on
      body mass index and data were compared using the paired t-test and Spearman rho.
      RESULTS: Of 101 patients 50 (50%) were obese (body mass index 30 kg/m(2) or
      greater). Median body mass index was 25.6 kg/m(2) in the nonobese cohort and 38.3
      kg/m(2) in the obese cohort. Average peak inspiratory pressure while supine and
      prone was 18.0 and 18.5 cm H2O in the nonobese cohort, and 25.5 and 26.6 cm H2O,
      respectively, in the obese cohort. Obese patients had significantly higher peak
      inspiratory pressure in the supine and the prone positions relative to nonobese
      patients (p <0.0001). However, there was no change in peak inspiratory pressure
      from the supine to the prone position in either cohort. CONCLUSIONS: Obese
      patients have higher baseline peak inspiratory pressure regardless of position.
      However, prone positioning does not impact peak inspiratory pressure in either
      cohort. It remains a safe and viable option.

PMID- 25983194
TI  - Patterns of Local Failure following Radiation Therapy for Prostate Cancer.
AB  - PURPOSE: Little is known about patterns of local failure following radiation
      therapy for prostate cancer. We aimed to characterize post-radiation biopsy
      findings, including the treatment effect and the zonal distribution of recurrent
      disease after radiation therapy, in men experiencing biochemical recurrence.
      MATERIALS AND METHODS: We identified patients who received post-radiation biopsy
      in the setting of biochemical recurrence following primary radiation for
      localized disease. Histological post-radiation biopsy results were categorized by
      the absence of tumor, demonstration of radiation treatment effect, failure
      (recurrent cancer) or a combination of treatment effect and failure. We described
      patterns of histological failure and compared them to the diagnostic biopsy
      findings. RESULTS: A total of 284 men underwent mapped post-radiation biopsy for
      biochemical recurrence. Mean age at initial diagnosis was 63 years and median
      prostate specific antigen was 8.2 ng/ml. Of the men 33%, 32% and 35% were
      classified at low, intermediate and high risk based on clinical CAPRA (Cancer of
      the Prostate Risk Assessment) categories. Median time to post-radiation biopsy
      was 61 months after treatment. Findings were negative in 4% of cases while we
      noted a treatment effect in 31%, failure in 45% and a combination in 20%. Failure
      rates were similar across sextants. Of 140 patients with mapped pretreatment and
      posttreatment biopsies 4% demonstrated cancer in a new location previously
      identified as negative. Gleason upgrading occurred in 43% of cases with 85%
      upgraded to 4 + 3 or higher. CONCLUSIONS: Men with rising prostate specific
      antigen after radiotherapy for prostate cancer most often experience recurrence
      in dominant tumor sites. Whether failure is due to inadequate targeting, dosing
      or intrinsic radiation resistance remains unknown to our knowledge. Further study
      is warranted.

PMID- 25983195
TI  - Neuroimmunomodulation: A new frontier of treating cardiovascular diseases.

PMID- 25983196
TI  - A probabilistic approach for a cost-benefit analysis of oil spill management
      under uncertainty: A Bayesian network model for the Gulf of Finland.
AB  - Large-scale oil accidents can inflict substantial costs to the society, as they
      typically result in expensive oil combating and waste treatment operations and
      have negative impacts on recreational and environmental values. Cost-benefit
      analysis (CBA) offers a way to assess the economic efficiency of management
      measures capable of mitigating the adverse effects. However, the irregular
      occurrence of spills combined with uncertainties related to the possible effects
      makes the analysis a challenging task. We develop a probabilistic modeling
      approach for a CBA of oil spill management and apply it in the Gulf of Finland,
      the Baltic Sea. The model has a causal structure, and it covers a large number of
      factors relevant to the realistic description of oil spills, as well as the costs
      of oil combating operations at open sea, shoreline clean-up, and waste treatment
      activities. Further, to describe the effects on environmental benefits, we use
      data from a contingent valuation survey. The results encourage seeking for cost
      effective preventive measures, and emphasize the importance of the inclusion of
      the costs related to waste treatment and environmental values in the analysis.
      Although the model is developed for a specific area, the methodology is
      applicable also to other areas facing the risk of oil spills as well as to other
      fields that need to cope with the challenging combination of low probabilities,
      high losses and major uncertainties. 

PMID- 25983197
TI  - Re: Comparison of automated versus traditional nerve conduction study methods for
      median nerve testing in a general worker population.

PMID- 25983198
TI  - Reply: To PMID 25463687.

PMID- 25983200
TI  - Physiology and evidence join in favor of prone decubitus.

PMID- 25983199
TI  - Fluorofenidone inhibits macrophage IL-1beta production by suppressing
      inflammasome activity.
AB  - Interleukin-1 beta (IL-1beta) is a potent pro-inflammatory and pro-fibrotic
      cytokine that plays an important role in renal fibrosis. Fluorofenidone (AKF-PD)
      is a novel pyridone agent that exerts a strong renal anti-fibrotic effect. We
      previously found that administration of AKF-PD could significantly attenuate IL
      1beta production in vitro and in vivo. However, the underlying mechanism is not
      fully understood. Here we show that AKF-PD has no effect on the expression of pro
      IL-1beta in activated mouse macrophages in vitro. Instead, AKF-PD inhibits the
      inflammasome, lowering caspase-1 levels and thereby decreasing cleavage of pro-IL
      1beta into IL-1beta. AKF-PD was found to block inflammasome activity induced by
      various signals, including ATP, alum crystals, and Salmonella typhimurium. These
      results provide a novel mechanistic insight into how AKF-PD exerts its anti
      inflammatory and anti-fibrotic activities, and suggest that AKF-PD might block IL
      1beta production via suppression of inflammasomes in renal fibrosis. In addition,
      the results suggest that AKF-PD may be of therapeutic potential in other
      inflammasome-related diseases. 

PMID- 25983201
TI  - [Extracorporeal membrane oxygenation ventricular support as a bridge to ablation
      in refractory cardiogenic shock refractory to tachycardia-induce cardiomyopathy].

PMID- 25983202
TI  - [Pulmonary artery leiomyosarcoma: Uncommon and difficult to diagnose].

PMID- 25983203
TI  - A new method for spike extraction using velocity selective recording demonstrated
      with physiological ENG in Rat.
AB  - BACKGROUND: This paper describes a series of experiments designed to verify a new
      method of electroneurogram (ENG) recording that enables the rate of neural firing
      within prescribed bands of propagation velocity to be determined in real time.
      Velocity selective recording (VSR) has been proposed as a solution to the problem
      of increasing the information available from an implantable neural interface
      (typically with electrodes in circumferential nerve cuffs) and has been
      successful in transforming compound action potentials into the velocity domain.
      NEW METHOD: The new method extends VSR to naturally-evoked (physiological) ENG in
      which the rate of neural firing at particular velocities is required in addition
      to a knowledge of the velocities present in the recording. RESULTS: The
      experiments, carried out in rats required individual spikes to be distinct and
      non-overlapping, which could be achieved by a microchannel or small-bore cuff. In
      these experiments, strands of rat nerve were laid on ten hook electrodes in oil
      to demonstrate the principle. COMPARISON WITH EXISTING METHOD: The new method
      generates a detailed overview of the firing rates of neurons based on their
      conduction velocity and direction of propagation. In addition it allows real time
      working in contrast to existing spike sorting methods using statistical pattern
      processing techniques. CONCLUSIONS: Results show that by isolating neural
      activity based purely on conduction velocity it was possible to determine the
      onset of direct cutaneous stimulation of the L5 dermatome.

PMID- 25983204
TI  - Individuals with chronic low back pain demonstrate delayed onset of the back
      muscle activity during prone hip extension.
AB  - Prone hip extension (PHE) is commonly used in the evaluation of the stability of
      the lumbopelvic region. There is little evidence of difference in muscle activity
      onset timing between healthy individuals and individuals with chronic low back
      pain (CLBP) during PHE. The purpose of this study was to determine if individuals
      with and without CLBP differ in the onset time of the trunk and hip extensor
      muscles activity during PHE. The participants were 20 patients with CLBP and 20
      healthy individuals. Electromyography data of the erector spinae, multifidus,
      gluteus maximus, and semitendinosus were collected during PHE using a surface
      electromyograph. Relative differences in the onset times between each muscle and
      the prime mover (i.e., the semitendinosus) were calculated. The onsets of the
      bilateral multifidus and contralateral erector spinae were significantly delayed
      in the CLBP group compared with the healthy group (p<0.001), despite the onset
      timings of leg movement not being significantly different between the groups. The
      onset times of the gluteus maximus and ipsilateral erector spinae showed no
      significant differences between the groups. These results suggest that
      individuals with CLBP use an altered, and possibly inadequate, trunk muscle
      recruitment pattern. 

PMID- 25983205
TI  - A cooperative system of silicon transport in plants.
AB  - The high accumulation of silicon (Si) protects plants from biotic and abiotic
      stresses. Two different types of Si transporter [Low Silicon 1 (Lsi1) and 2
      (Lsi2)] involved in the uptake and distribution of Si have been identified. Lsi1,
      a Si permeable channel, belongs to the Nod26-like major intrinsic protein (NIP)
      III subgroup of the aquaporin membrane protein family with a distinct
      selectivity, whereas Lsi2, an efflux Si transporter, belongs to an
      uncharacterized anion transporter family. These transporters are localized to the
      plasma membrane, but, in different plant species, show different expression
      patterns and tissue or cellular localizations that are associated with different
      levels of Si accumulation. A recent mathematical modeling study revealed that
      cooperation of Lsi1 and Lsi2, which show a polarized localization, is required
      for the efficient transport of Si in rice.

PMID- 25983206
TI  - Diversification of histone H2A variants during plant evolution.
AB  - Among eukaryotes, the four core histones show an extremely high conservation of
      their structure and form nucleosomes that compact, protect, and regulate access
      to genetic information. Nevertheless, in multicellular eukaryotes the two
      families, histone H2A and histone H3, have diversified significantly in key
      residues. We present a phylogenetic analysis across the green plant lineage that
      reveals an early diversification of the H2A family in unicellular green algae and
      remarkable expansions of H2A variants in flowering plants. We define motifs and
      domains that differentiate plant H2A proteins into distinct variant classes. In
      non-flowering land plants, we identify a new class of H2A variants and propose
      their possible role in the emergence of the H2A.W variant class in flowering
      plants.

PMID- 25983208
TI  - Bulbosum to Go: A Toolbox to Utilize Hordeum vulgare/bulbosum Introgressions for
      Breeding and Beyond.
AB  - Hordeum bulbosum L., a wild relative of barley (Hordeum vulgare L.), has been
      considered as a valuable source of genetic diversity for barley improvement.
      Since the 1990s, a considerable number of barley/H. bulbosum introgression lines
      (IL)s has been generated, with segments introgressed from H. bulbosum harboring a
      diverse set of desirable traits. However, the efficient utilization of these ILs
      has been hampered, largely due to the lack of suitable molecular tools for their
      genetic characterization and highly reduced interspecific recombination
      frequencies in the region of the introgression. In the present study, we utilized
      genotyping-by-sequencing for the detailed molecular characterization of 145 ILs.
      Genotypic information allows the genetic diversity within the set of ILs to be
      determined and a strategy was outlined to tackle the obstacle of reduced
      recombination frequencies. Furthermore, we compiled exome capture re-sequencing
      information of barley and H. bulbosum and designed an integrated barley/H.
      bulbosum sequence resource with polymorphism information on interspecific and
      intraspecific sequence variations of both species. The integrated sequence will
      be valuable for marker development in barley/H. bulbosum ILs derived from any
      barley and H. bulbosum donors. This study provides the tools for the widespread
      utilization of barley/H. bulbosum ILs in applied barley breeding and academic
      research.

PMID- 25983209
TI  - A 23-year, single-center, retrospective analysis of 36 cases of acute
      pancreatitis in pregnancy.
AB  - OBJECTIVE: To assess the incidence, causes, clinical characteristics, and
      outcomes of cases of acute pancreatitis in pregnancy (APIP). METHODS: A
      retrospective review was conducted of the medical records of pregnant women who
      were diagnosed with APIP at any point during pregnancy, labor, or the puerperium
      and attended Beijing Chaoyang Hospital, China, between January 1, 1991, and March
      31, 2014. RESULTS: Among 34 292 pregnant women admitted to the center during the
      study period, 36 patients were diagnosed with APIP. The condition developed
      during the second (9 [25%] cases) and third (22 [61%]) trimesters. The underlying
      cause was hypertriglyceridemia for 14 (39%) patients and biliary diseases for 7
      (19%). Severe acute pancreatitis was significantly more common among patients
      with hypertriglyceridemia (11/14 [79%]) than among those without
      hypertriglyceridemia (6/22 [27%]; P=0.006). Additionally, complications were
      recorded for more patients with hypertriglyceridemia (11 [79%]) than those
      without hypertriglyceridemia (4 [18%]; P<0.001). Delayed diagnosis was more
      common among patients with severe acute pancreatitis (8/17 [47%]) than among
      those with mild acute pancreatitis (3/19 [16%]; P=0.039). No maternal deaths and
      only two perinatal deaths were recorded. CONCLUSION: The overall incidence of
      APIP was low; however, hypertriglyceridemia was associated with poor outcomes.
      Early diagnosis and prompt treatment should be implemented to improve maternal
      and fetal prognosis and decrease mortality.

PMID- 25983210
TI  - Vaginal bleeding associated with antidepressants.

PMID- 25983207
TI  - SAUR Proteins as Effectors of Hormonal and Environmental Signals in Plant Growth.
AB  - The plant hormone auxin regulates numerous aspects of plant growth and
      development. Early auxin response genes mediate its genomic effects on plant
      growth and development. Discovered in 1987, small auxin up RNAs (SAURs) are the
      largest family of early auxin response genes. SAUR functions have remained
      elusive, however, presumably due to extensive genetic redundancy. However, recent
      molecular, genetic, biochemical, and genomic studies have implicated SAURs in the
      regulation of a wide range of cellular, physiological, and developmental
      processes. Recently, crucial mechanistic insight into SAUR function was provided
      by the demonstration that SAURs inhibit PP2C.D phosphatases to activate plasma
      membrane (PM) H(+)-ATPases and promote cell expansion. In addition to auxin,
      several other hormones and environmental factors also regulate SAUR gene
      expression. We propose that SAURs are key effector outputs of hormonal and
      environmental signals that regulate plant growth and development.

PMID- 25983211
TI  - The effects of resource improvement on decision-to-delivery times for cesarean
      deliveries in a Ghanaian regional hospital.
AB  - OBJECTIVE: To evaluate the effects of having a dedicated obstetric operating room
      (OR) on the decision-to-delivery interval (DDI) in a large referral hospital in
      Ghana. METHODS: An observational study was undertaken of all patients undergoing
      cesarean delivery at Ridge Regional Hospital, Accra, before (pre-OR; August
      September 2011) and after (post-OR; August-September 2012) introduction of an
      obstetric OR. The primary outcome was the DDI. RESULTS: In total, 581 cesareans
      were performed in the pre-OR period and 574 in the post-OR period. Overall, the
      median DDI decreased from 259 min (interquartile range [IQR] 161-432) in the pre
      OR period to 195 min (IQR 138-319) in the post-OR period (P<0.001). DDI was lower
      in the post-OR period than in the pre-OR period for both emergency (175 min [IQR
      126-241] vs 220 min [IQR 146-315]; P<0.001) and elective (1828 min [IQR 1432
      2985] vs 4291 min [IQR 2992-5862]; P<0.001) cesarean deliveries. Only one
      emergency cesarean-in the post-OR period-was conducted within the recommended 30
      minute timeframe. CONCLUSION: An obstetric OR lowered the DDI for cesarean
      delivery; however, a realistic timeframe for emergency cesareans in low-income
      countries remains to be determined.

PMID- 25983212
TI  - Using electronic readers to monitor progress toward elimination of mother-to
      child transmission of HIV and syphilis: An opinion piece.
AB  - Electronic readers and smartphones have the potential to standardize the
      interpretation of rapid diagnostic tests (RDTs) and provide timely surveillance
      program data. RDTs are widely used for HIV and are being increasingly used for
      syphilis screening in pregnant women. Following the WHO initiative for the
      validation of elimination of mother-to-child transmission of HIV and syphilis,
      there is a need for more extensive testing and data monitoring. However, access
      to timely and accurate data can be challenging once testing is decentralized as
      data quality at remote sites is often difficult to verify. Electronic RDT readers
      can help to ensure quality and allow automated data transmission, creating an
      opportunity for real-time surveillance to inform control strategies and assess
      intervention impact. Furthermore, by linking the data to existing supply chain
      management software, stockouts can be minimized. The present opinion piece looks
      at the opportunities and challenges of using these tools within national
      elimination programs. 

PMID- 25983213
TI  - Reliability and validity of a Chinese version of the Modified Body Image Scale in
      patients with symptomatic pelvic organ prolapse.
AB  - OBJECTIVE: To validate a Chinese version of the Modified Body Image Scale (MBIS)
      among patients with symptomatic pelvic organ prolapse. METHODS: As part of a
      validation study at a center in Beijing, China, women with symptomatic pelvic
      organ prolapse stage II or greater completed the Chinese version of the MBIS, the
      12-item Short-Form Health Survey (SF-12), and the Pelvic Organ Prolapse/Urinary
      Incontinence Sexual Questionnaire (PISQ-12). A sample of 30 women was randomly
      chosen to return 2weeks later to complete the questionnaires again. The
      reliability and validity of the MBIS were assessed. RESULTS: Overall, 52 patients
      participated. A Cronbach alpha of 0.926 demonstrated adequate internal
      consistency of the Chinese MBIS. Its reproducibility was demonstrated by
      intraclass correlation coefficient values of 0.554-0.963 (P<0.01 for all items).
      Confirmatory factor analysis supported its construct validity. The MBIS and SF-12
      scores were negatively correlated (r=-0.390; P<0.001), and the MBIS and PISQ-12
      scores were also negatively correlated (r=-0.709; P<0.001). CONCLUSION: The
      Chinese version of the MBIS is a reliable and valid tool to evaluate body image
      perception among patients with symptomatic pelvic organ prolapse.

PMID- 25983214
TI  - Human Tear Serotonin Levels Correlate with Symptoms and Signs of Dry Eye.
AB  - PURPOSE: Serotonin, a neurotransmitter known to be involved in nociceptor
      sensitization, is present in human tears. The purpose of this study was to
      correlate tear serotonin levels, as a marker of nociceptor sensitization, to
      facets of dry eye (DE), including symptoms and signs. DESIGN: Cross-sectional
      study. PARTICIPANTS: A total of 62 patients with normal eyelid and corneal
      anatomy were prospectively recruited from a Veterans Administration Ophthalmology
      Clinic over 11 months. METHODS: Dry eye symptoms (Ocular Surface Disease Index
      [OSDI]), signs (tear break-up time [TBUT], corneal staining, and Schirmer's
      score), and clinical descriptors of neuropathic ocular pain (NOP) (sensitivity to
      light or sensitivity to wind) were assessed. For tear analysis, each patient's
      tears were collected after instilling 50 MUl of sterile saline to the lower cul
      de-sac of each eye and using capillary action microcaps to collect the ocular
      wash. Tear serotonin levels were measured using enzyme-linked immunosorbent
      assay. MAIN OUTCOME MEASURES: Correlations between tear serotonin concentrations
      and DE symptoms and signs. RESULTS: The mean age of the population was 61+/-14
      years, and 84% (n = 52) of the patients were male. Serotonin concentrations
      negatively correlated with Schirmer's scores (r = -0.28; P = 0.02) but did not
      correlate with other DE parameters, such as OSDI scores, sensitivity to light or
      wind, TBUT, and staining. According to our hypothesis, we divided patients into
      groups based on both DE symptoms and aqueous tear production; serotonin
      concentrations were significantly higher in DE group 1 (OSDI >=6 and Schirmer's
      <8) compared with both DE group 2 (OSDI >=6 and Schirmer's >=8) and controls
      (OSDI <6 and Schirmer's >=8). Patients in DE group 2 more frequently reported
      sensitivity to light (64%) and wind (67%) compared with DE group 1 (40% and 60%,
      respectively) and controls (8% and 17%, respectively). CONCLUSIONS: Patients with
      DE symptoms and aqueous tear deficiency had higher tear serotonin levels compared
      with those with DE symptoms but normal tear production and those without DE
      symptoms.

PMID- 25983215
TI  - Increasing Prevalence of Myopia in Europe and the Impact of Education.
AB  - PURPOSE: To investigate whether myopia is becoming more common across Europe and
      explore whether increasing education levels, an important environmental risk
      factor for myopia, might explain any temporal trend. DESIGN: Meta-analysis of
      population-based, cross-sectional studies from the European Eye Epidemiology
      (E(3)) Consortium. PARTICIPANTS: The E(3) Consortium is a collaborative network
      of epidemiological studies of common eye diseases in adults across Europe.
      Refractive data were available for 61 946 participants from 15 population-based
      studies performed between 1990 and 2013; participants had a range of median ages
      from 44 to 78 years. METHODS: Noncycloplegic refraction, year of birth, and
      highest educational level achieved were obtained for all participants. Myopia was
      defined as a mean spherical equivalent <=-0.75 diopters. A random-effects meta
      analysis of age-specific myopia prevalence was performed, with sequential
      analyses stratified by year of birth and highest level of educational attainment.
      MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing
      years of birth and educational level. RESULTS: There was a significant cohort
      effect for increasing myopia prevalence across more recent birth decades; age
      standardized myopia prevalence increased from 17.8% (95% confidence interval
      [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939
      compared with 1940 and 1979 (P = 0.03). Education was significantly associated
      with myopia; for those completing primary, secondary, and higher education, the
      age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5),
      and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were
      more educated, this did not fully explain the cohort effect. Compared with the
      reference risk of participants born in the 1920s with only primary education,
      higher education or being born in the 1960s doubled the myopia prevalence ratio
      2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals
      born in the 1960s and completing higher education had approximately 4 times the
      reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). CONCLUSIONS: Myopia
      is becoming more common in Europe; although education levels have increased and
      are associated with myopia, higher education seems to be an additive rather than
      explanatory factor. Increasing levels of myopia carry significant clinical and
      economic implications, with more people at risk of the sight-threatening
      complications associated with high myopia.

PMID- 25983216
TI  - The REVEAL Study: Ranibizumab Monotherapy or Combined with Laser versus Laser
      Monotherapy in Asian Patients with Diabetic Macular Edema.
AB  - OBJECTIVE: The primary study hypothesis was that ranibizumab 0.5 mg monotherapy
      or combined with laser is superior to laser monotherapy based on mean average
      change in best-corrected visual acuity (BCVA) over 12 months in Asian patients
      with visual impairment resulting from diabetic macular edema (DME). DESIGN: A 12
      month, randomized, double-masked, multicenter, laser-controlled, phase III study.
      PARTICIPANTS: Three hundred ninety-six patients aged >=18 years, with type 1 or 2
      diabetes mellitus, BCVA of 78-39 Early Treatment Diabetic Retinopathy Study
      (ETDRS) letters, and visual impairment resulting from DME. METHODS: Patients were
      randomized to ranibizumab + sham laser (n = 133), ranibizumab + active laser (n =
      132), or sham injection + active laser (n = 131). Ranibizumab/sham injections
      were administered on day 1 and continued monthly. As of month 3, monthly
      injections were continued if stable vision was not reached. Treatment was
      reinitiated if BCVA decreased because of DME progression. Active/sham laser was
      administered on day 1 and thereafter according to ETDRS guidelines. MAIN OUTCOME
      MEASURES: Average change in BCVA from baseline to months 1 through 12, central
      retinal subfield thickness (CRST), and safety over 12 months. RESULTS:
      Ranibizumab monotherapy or combined with laser was superior to laser in improving
      mean average change in BCVA from baseline to months 1 through 12 (+5.9 and +5.7
      vs +1.4 letters). At month 12, greater proportion of patients gained >=15 letters
      with ranibizumab and ranibizumab + laser compared with laser (18.8% and 17.8% vs
      7.8%). Mean CRST reduced significantly from baseline to month 12 with ranibizumab
      (-134.6 MUm) and ranibizumab + laser (-171.8 MUm) versus laser (-57.2 MUm).
      Patients received a mean of 7.8 and 7.0 ranibizumab injections in the ranibizumab
      and ranibizumab + laser arms, respectively, and 1.5-1.9 active laser across
      treatment arms over 12 months. Conjunctival hemorrhage was the most common
      ocular, whereas nasopharyngitis and hypertension were the most common nonocular
      adverse events. Ranibizumab was not associated with any cases of cerebrovascular
      hemorrhage and cerebrovascular ischemia. No death related to study treatment was
      reported. CONCLUSIONS: Ranibizumab monotherapy or combined with laser showed
      superior BCVA improvements over laser treatment alone in Asian patients with
      visual impairment resulting from DME. No new ocular or nonocular safety findings
      were observed and treatment was well tolerated over 12 months.

PMID- 25983218
TI  - Clinical trials supported by the Tinnitus Research Consortium: Lessons learned,
      the Southern Illinois University experience.
AB  - The Tinnitus Research Consortium funded three clinical trials investigating
      treatments for chronic bothersome tinnitus at Southern Illinois University School
      of Medicine. The trials were designed to measure the subjective changes in
      tinnitus distress using standardized questionnaires and objective changes in
      tinnitus loudness using psychophysical matching procedures. The results of the
      first two trials have been published and are summarized here. The first trial
      investigated the effect of gabapentin on the loudness and annoyance of tinnitus
      in adults with chronic bothersome tinnitus with and without a history of acoustic
      trauma. A small but significant number of subjects reported decreased tinnitus
      annoyance that corresponded with a decrease in objective measures of tinnitus
      loudness during active drug treatment with a washout effect during placebo
      treatment. The second trial compared the effect of tinnitus retraining therapy
      (TRT) on adults with normal to near-normal hearing and chronic bothersome
      tinnitus to treatment with general counseling without acoustic enrichment.
      Significant improvements in tinnitus severity, but not in objective psychometric
      measures of tinnitus loudness, occurred in both treatment groups, however a
      greater effect was observed in the TRT group compared with the control group. The
      third trial is nearing completion and investigates the long-term results of
      tinnitus retraining therapy on chronic bothersome tinnitus in adults with hearing
      loss. Significant lessons and observations on conducting tinnitus clinical trials
      were learned from these three trials. The challenges of recruiting and retaining
      study participants is discussed. More importantly, the reliability and stability
      of the Tinnitus Handicap Inventory (THI) over long intervals is presented. The
      implications of this variability for the design and interpretation of future
      tinnitus studies is discussed. This article is part of a Special Issue entitled
      <Tinnitus>.

PMID- 25983217
TI  - High-Throughput Microfluidic Platform for 3D Cultures of Mesenchymal Stem Cells,
      Towards Engineering Developmental Processes.
AB  - The development of in vitro models to screen the effect of different
      concentrations, combinations and temporal sequences of morpho-regulatory factors
      on stem/progenitor cells is crucial to investigate and possibly recapitulate
      developmental processes with adult cells. Here, we designed and validated a
      microfluidic platform to (i) allow cellular condensation, (ii) culture 3D
      micromasses of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs)
      under continuous flow perfusion, and (ii) deliver defined concentrations of
      morphogens to specific culture units. Condensation of hBM-MSCs was obtained
      within 3 hours, generating micromasses in uniform sizes (56.2 +/- 3.9 MUm). As
      compared to traditional macromass pellet cultures, exposure to morphogens
      involved in the first phases of embryonic limb development (i.e. Wnt and FGF
      pathways) yielded more uniform cell response throughout the 3D structures of
      perfused micromasses (PMMs), and a 34-fold higher percentage of proliferating
      cells at day 7. The use of a logarithmic serial dilution generator allowed to
      identify an unexpected concentration of TGFbeta3 (0.1 ng/ml) permissive to hBM
      MSCs proliferation and inductive to chondrogenesis. This proof-of-principle study
      supports the described microfluidic system as a tool to investigate processes
      involved in mesenchymal progenitor cells differentiation, towards a
      'developmental engineering' approach for skeletal tissue regeneration.

PMID- 25983219
TI  - Item-nonspecific proactive interference in monkeys' auditory short-term memory.
AB  - Recent studies using the delayed matching-to-sample (DMS) paradigm indicate that
      monkeys' auditory short-term memory (STM) is susceptible to proactive
      interference (PI). During the task, subjects must indicate whether sample and
      test sounds separated by a retention interval are identical (match) or not
      (nonmatch). If a nonmatching test stimulus also occurred on a previous trial,
      monkeys are more likely to incorrectly make a "match" response (item-specific
      PI). However, it is not known whether PI may be caused by sounds presented on
      prior trials that are similar, but nonidentical to the current test stimulus
      (item-nonspecific PI). This possibility was investigated in two experiments. In
      Experiment 1, memoranda for each trial comprised tones with a wide range of
      frequencies, thus minimizing item-specific PI and producing a range of frequency
      differences among nonidentical tones. In Experiment 2, memoranda were drawn from
      a set of eight artificial sounds that differed from each other by one, two, or
      three acoustic dimensions (frequency, spectral bandwidth, and temporal dynamics).
      Results from both experiments indicate that subjects committed more errors when
      previously-presented sounds were acoustically similar (though not identical) to
      the test stimulus of the current trial. Significant effects were produced only by
      stimuli from the immediately previous trial, suggesting that item-nonspecific PI
      is less perseverant than item-specific PI, which can extend across noncontiguous
      trials. Our results contribute to existing human and animal STM literature
      reporting item-nonspecific PI caused by perceptual similarity among memoranda.
      Together, these observations underscore the significance of both temporal and
      discriminability factors in monkeys' STM. 

PMID- 25983220
TI  - Microvascular free tissue transfer in acute and secondary burn reconstruction.
AB  - INTRODUCTION: The mainstay of operative treatment in burns is split skin grafting
      with free tissue transfer being indicated in a minority of cases. However, free
      tissue transfer faces a number of challenges in the burns patient. These include;
      overall cardiovascular and respiratory stability of the patient, availability of
      suitable vessels for anastomosis, sufficient debridement of devitalised tissue
      and a potentially increased risk of infection. We carried out a retrospective
      study in order to determine the indications, timing, principles of flap
      selection, complications, outcomes and methods of promoting flap survival when
      free tissue transfer was utilised for burn reconstruction in our unit. MATERIALS
      AND METHODS: All patients who underwent soft tissue reconstruction for burn
      injuries with microvascular free tissue transfer between May 2002 and September
      2014 were identified from our burns database. The records of these patients were
      then retrospectively reviewed. Data extracted included, age, gender, type of
      injury, total body surface area involved, indications for free tissue transfer,
      anatomical location, timing of reconstruction, complications and flap survival.
      RESULTS: Out of a total of 8776 patients admitted for operative treatment over a
      12-year period, 23 patients required 26 free flaps for reconstruction. Out of 26
      free flaps, 23 were utilised for acute burn reconstruction while only 3 free
      flaps were utilised for secondary burn reconstruction. All 26 free flaps survived
      regardless of timing or burn injury mechanism. Complications included haematomas
      in 2 flaps and tip necrosis in 4 flaps. Two flaps required debridement and
      drainage of pus, 1 flap required redo of the venous anastomosis while 1 required
      redo of the arterial anastomosis with a vein graft. CONCLUSIONS: Free tissue
      transfer has a small but definite role within acute and secondary burn
      reconstruction surgery. Despite the complexity of the burn defects involved, free
      flaps appear to have a high success rate within this cohort of patients. This
      appears to be the case as long as the appropriate patient and flap is selected,
      care is taken to debride all devitalised tissue and due diligence paid to the
      vascular anastomosis by performing it away from the zone of injury.

PMID- 25983221
TI  - To drain or not to drain? Predictors of tube thoracostomy insertion and outcomes
      associated with drainage of traumatic hemothoraces.
AB  - INTRODUCTION: Historical data suggests that many traumatic hemothoraces (HTX) can
      be managed expectantly without tube thoracostomy (TT) drainage. The purpose of
      this study was to identify predictors of TT, including whether the quantity of
      pleural blood predicted tube placement, and to evaluate outcomes associated with
      TT versus expected management (EM) of traumatic HTXs. PATIENTS AND METHODS: A
      retrospective cohort study of all trauma patients with HTXs and an Injury
      Severity Score (ISS) >=12 managed at a level I trauma centre between April 1,
      2005 and December 31, 2012 was completed. Mixed-effects models with a subject
      specific random intercept were used to identify independent risk factors for TT.
      Logistic and log-linear regression were used to compute odds ratios (ORs) for
      mortality and empyema and percent increases in length of hospital and intensive
      care unit stay between patients managed with TT versus EM, respectively. RESULTS:
      A total of 635 patients with 749 HTXs were included in the study. Overall, 491
      (66%) HTXs were drained while 258 (34%) were managed expectantly. Independent
      predictors of TT placement included concomitant ipsilateral flail chest [OR 3.03;
      95% confidence interval (CI) 1.04-8.80; p=0.04] or pneumothorax (OR 6.19; 95% CI
      1.79-21.5; p<0.01) and the size of the HTX (OR per 10cc increase 1.12; 95% CI
      1.04-1.21; p<0.01). Although the adjusted odds of mortality were not
      significantly different between groups (OR 3.99; 95% CI 0.87-18.30; p=0.08), TT
      was associated with a 47.14% (95% CI, 25.57-69.71%; p<0.01) adjusted increase in
      hospital length of stay. Empyemas (n=29) only occurred among TT patients.
      CONCLUSIONS: Expectant management of traumatic HTX was associated with a shorter
      length of hospital stay, no empyemas, and no increase in mortality. Although EM
      of smaller HTXs may be safe, these findings must be confirmed by a large multi
      centre cohort study and randomized controlled trials before they are used to
      guide practice.

PMID- 25983222
TI  - Lactic acid production from acidogenic fermentation of fruit and vegetable
      wastes.
AB  - This work focused on the lactic acid production from acidogenic fermentation of
      fruit and vegetable wastes treatment. A long term completely stirred tank reactor
      (CSTR) lasting for 50 days was operated at organic loading rate (OLR) of 11
      gVS/(L d) and sludge retention time (SRT) of 3 days with pH controlled at 4.0 (1
      24 day) and 5.0 (25-50 day). The results indicated that high amount of
      approximately 10-20 g/L lactic acid was produced at pH of 4.0 and the
      fermentation type converted from coexistence of homofermentation and
      heterofermentation into heterofermentation. At pH of 5.0, the hydrolysis reaction
      was improved and the total concentration of fermentation products increased up to
      29.5 g COD/L. The heterofermentation was maintained, however, bifidus pathway by
      Bifidobacterium played an important role.

PMID- 25983223
TI  - Hemp hurds biorefining: A path to green L-(+)-lactic acid production.
AB  - Sugars streams generated by organosolv pretreatment of hemp hurds, cellulose (C6)
      and hemicellulose (C5) fractions, were fermented to lactic acid (LA) by Bacillus
      coagulans strains XZL4 and DSM1. Pretreatment conditions and enzymatic hydrolysis
      were optimized and B. coagulans aptness to use lignocellulosic-derived sugars as
      a carbon source was evaluated. Methanolic organosolv pretreatment with 2.5% (w/w)
      H2SO4 gave the best results in terms of glucan recovery (98%), enzymatic
      hydrolysis of pretreated biomass (70%) and hemicellulosic sugars recovery (61%).
      C6 and C5 sugars fermentation by strain XZL4 gave, high LA yields (0.90 and 0.84
      g/g), high titers (141 and 109 g/L), and high enantiomeric excess (>99%).
      Overall, 42 g of l-LA were obtained from 100 g of raw hemp hurds. These results
      can be considered promising for lignocellulosic feedstock valorization toward the
      production of polymer-grade LA.

PMID- 25983224
TI  - Physicochemical characterization of wet microalgal cells disrupted with instant
      catapult steam explosion for lipid extraction.
AB  - Instant catapult steam explosion (ICSE) was employed to disrupt wet microalgal
      cells for efficient lipid extraction. Physicochemical properties of exploded
      cells were investigated through SEM, TEM, FTIR, and TGA. The exploded cells
      increased in fractal dimension (1.53-1.65) when preheat time was prolonged from 0
      min to 5 min and in surface pore area when steam pressure was increased.
      Meanwhile, the exploded cells decreased in mean size (1.69-1.44 MUm) when the
      filling ratio of wet microalgal biomass in the preheat chamber decreased (75
      12.5%). Flash evaporation and volume expansion exploded the cell walls and
      released the cytoplasm of the microalgal cells. These phenomena decreased the
      carbohydrate content and increased the lipid content in the exploded biomass.
      However, ICSE treatment did not change the lipid compositions in the microalgal
      cells. Using isopropanol as a cosolvent significantly increased the yield of
      lipids extracted with hexane from the exploded wet microalgal biomass.

PMID- 25983225
TI  - Effects of CeO2 nanoparticles on biological nitrogen removal in a sequencing
      batch biofilm reactor and mechanism of toxicity.
AB  - The effects of CeO2 nanoparticles (CeO2 NPs) exposure on biological nitrogen
      removal in a sequencing batch biofilm reactor (SBBR) were investigated. At low
      concentration (1 mg/L), no significant effect was observed on total nitrogen (TN)
      removal. However, at high concentrations (10 and 50 mg/L), the TN removal
      efficiency reduced from 74.09% to 64.26% and 55.17%, respectively. Scanning
      electron microscope imaging showed large amounts of CeO2 NPs adsorbed on the
      biofilm, which increased the production of reactive oxygen species. The exposure
      at only 50 mg/L CeO2 NPs measurably affected the lactate dehydrogenase release.
      Confocal laser scanning microscopy showed that high concentrations of CeO2 NPs
      reduced bacterial viability. Moreover, after a short-term exposure, extracellular
      polymeric substances (EPS) were observed to increase, forming a compact matrix to
      protect the bacteria. The activities of nitrate reductase and ammonia
      monooxygenase were inhibited, but there was no significant impact on the activity
      of nitrite oxidoreductase.

PMID- 25983226
TI  - Cultivating and harvesting of marine alga Nannochloropsis oculata in local
      municipal wastewater for biodiesel.
AB  - The feasibility of using the mixture of seawater and municipal wastewater; (1)
      the wastewater before activated sludge tank, just after primary settling (BAS)
      and (2) the wastewater after activated sludge tank, just before addition of
      polymer flocculants (AAS); as culture medium for the cultivation of marine
      microalgae Nannochloropsis oculata was investigated. 10% BAS, 20% BAS and 10%
      AAS, 20% AAS, 50% AAS, 70% AAS, 100% AAS effluent loadings were well adapted to
      used wastewater. Sufficient dry weights obtained (345-406 mg L(-1)) with growth
      rates 0.37-0.45 for aerated cultures. High TN and TP removals (~74-90%) were
      achieved. Harvesting technique for grown cultures was also studied with natural
      sedimentation and pH induced flocculation. By alkalinity induced flocculation, at
      pH values of 10.50, high recovery of the cells (~80%) achieved with high
      sedimentation rates in 10 min. The flocculation efficiencies decreased,
      sedimentation rates increased with the increase of the cell concentration.

PMID- 25983227
TI  - Techno-economic analysis of advanced biofuel production based on bio-oil
      gasification.
AB  - This paper evaluates the economic feasibility of an integrated production pathway
      combining fast pyrolysis and bio-oil gasification. The conversion process is
      simulated with Aspen Plus(r) for a 2000 metric ton per day facility. Techno
      economic analysis of this integrated pathway has been conducted. A total capital
      investment of $510 million has been estimated and the minimum fuel selling price
      (MSP) is $5.59 per gallon of gasoline equivalent. The sensitivity analysis shows
      that the MSP is most sensitive to internal rate of return, fuel yield, biomass
      feedstock cost, and fixed capital investment. Monte-Carlo simulation shows that
      MSP for bio-oil gasification would be more than $6/gal with a probability of
      0.24, which indicates this pathway is still at high risk with current economic
      and technical situation. 

PMID- 25983228
TI  - A decision model for cost effective design of biomass based green energy supply
      chains.
AB  - The core driver of this study is to deal with the design of anaerobic digestion
      based biomass to energy supply chains in a cost effective manner. In this
      concern, a decision model is developed. The model is based on fuzzy multi
      objective decision making in order to simultaneously optimize multiple economic
      objectives and tackle the inherent uncertainties in the parameters and decision
      makers' aspiration levels for the goals. The viability of the decision model is
      explored with computational experiments on a real-world biomass to energy supply
      chain and further analyses are performed to observe the effects of different
      conditions. To this aim, scenario analyses are conducted to investigate the
      effects of energy crop utilization and operational costs on supply chain
      structure and performance measures. 

PMID- 25983229
TI  - Enhancing the power generation in microbial fuel cells with effective utilization
      of goethite recovered from mining mud as anodic catalyst.
AB  - Catalytic effect of goethite recovered from iron-ore mining mud was studied in
      microbial fuel cells (MFCs). Characterization of material recovered from mining
      mud confirms the recovery of iron oxide as goethite. Heat treated goethite (550 
      degrees C) and untreated raw goethite were coated on stainless-steel anode of MFC
      1 and MFC-2, respectively; whereas, unmodified stainless-steel anode was used in
      MFC-3 (control). Fivefold increment in power was obtained in MFC-1 (17.1 W/m(3)
      at 20 Omega) than MFC-3 (3.5 W/m(3)). MFC with raw goethite coated anode also
      showed enhanced power (11 W/m(3)). Higher Coulombic efficiency (34%) was achieved
      in MFC-1 than control MFC-3 (13%). Decrease in mass-transport losses and higher
      redox current during electrochemical analyses support improved electron transfer
      with the use of goethite on anode. Cheaper goethite coating kinetically
      accelerates the electron transfer between bacteria and anode, proving to be a
      novel approach for enhancing the electricity generation along with organic matter
      removal in MFC.

PMID- 25983230
TI  - Bio-harvesting and pyrolysis of the microalgae Botryococcus braunii.
AB  - The microalgae Botryococcus braunii is widely recognized as a potentially
      important biofuel-feedstock whose commercial exploitation is limited by
      difficulties with its cultivation and harvesting. In this study, two B. braunii
      strains, Kossou-4 and Overjuyo-3 were successfully cultured at a 500 l-scale for
      60-days. Harvesting by bio-flocculation with Aspergillus fumigatus at an optimum
      ratio of 1:40 of fungus to microalgal culture resulted in up to 98% recovery of
      biomass in the two strains. Ultimate analysis (C, N, H, S, ash, high heating
      value) and pyrolysis (analytical and preparative pyrolysis and GC-MS assays)
      showed that co-harvesting with fungi did not cause any impairment of the
      feedstock value of the microalgal biomass. This work represents the first report
      on the successful culturing and harvesting of these strains at a 500 l-scale
      using bio-flocculation. The use of A. fumigatus represents an efficient and
      economical method for the harvest of B. braunii for biofuel production.

PMID- 25983231
TI  - Microbiome frequency and their association with trypanosome infection in male
      Glossina morsitans centralis of Western Zambia.
AB  - Tsetse flies (Diptera: Glossinidae) are considered primary cyclical vectors that
      transmit pathogenic trypanosomes in Africa. They harbour a variety of microbes
      including Wolbachia, Sodalis and the salivary gland hypertrophy virus (SGHV)
      which are all vertically transmitted. Knowledge on tsetse microbiome and their
      interactions may identify novel strategies for tsetse fly and trypanosomiasis
      control. Area-wide application of such strategies requires an understanding of
      the natural microbiome frequency in the different species and subspecies of
      Glossina in their geographical populations. Consequently, this study determined
      the prevalence of Sodalis, Wolbachia, SGHV and trypanosome infections in Glossina
      morsitanscentralis from two sites of Western Zambia. We also explored possible
      associations of the microbes with trypanosome infections. Male G.
      morsitanscentralis samples were collected from two sites (Lyoni and Lusinina) in
      Western Zambia. The age structure of the flies at each site was determined using
      the wing fray method. DNA was extracted from the samples and analyzed for
      Wolbachia, Sodalis, SGHV and trypanosome presence using PCR. Associations and
      measures of associations between trypanosome infection and microbes in the fly
      were determined. The flies from the two locations (Lusinina, n=45 and Lyoni,
      n=24) had a similar age structure with their median fray category not being
      significantly different (p=0.698). The overall prevalence of Wolbachia was 72.5%
      (95% CI: 61.6-83.3%), Sodalis was 15.9% (95% CI: 7.1-24.8%), SGHV was 31.9% (95%
      CI: 20.6-43.2%) and Trypanosoma species was 23.2% (95% CI: 13-33.4%). The
      prevalence of Wolbachia was significantly higher in Lusinina than Lyoni
      (p=0.000). However this was not the case for Sodalis, SGHV and Trypanosoma
      species. Despite the low number of flies that were positive for both trypanosome
      and Sodalis (6; 8.7%), a statistically significant association (p=0.013; AOR 6.2;
      95% CI: 1.5-25.8) was observed in G. morsitanscentralis. The study showed that
      the prevalence of microbiota may vary within the same species of the tsetse
      depending on the geographical location as was the case of Wolbachia. Further it
      showed that infection with Sodalis could affect vector competence. The study
      concludes that Sodalis could be an ideal candidate for symbiont-mediated
      trypanosomiasis control interventions in G. morsitanscentralis. 

PMID- 25983232
TI  - In vitro levamisole selection pressure on larval stages of Haemonchus contortus
      over nine generations gives rise to drug resistance and target site gene
      expression changes specific to the early larval stages only.
AB  - There is some evidence that resistance to levamisole and pyrantel in
      trichostrongylid nematodes is due to changes in the composition of nicotinic
      acetylcholine receptors (nAChRs) which represent the drug target site. Altered
      expression patterns of genes coding for nAChR subunits, as well as the presence
      of truncated versions of several subunits, have been implicated in observed
      resistances. The studies have mostly compared target sites in worm isolates of
      very different genetic background, and hence the ability to associate the
      molecular changes with drug sensitivity alone have been clouded to some extent.
      The present study aimed to circumvent this issue by following target site gene
      expression pattern changes as resistance developed in Haemonchus contortus worms
      under laboratory selection pressure with levamisole. We applied drug selection
      pressure to early stage larvae in vitro over nine generations, and monitored
      changes in larval and adult drug sensitivities and target site gene expression
      patterns. High level resistance developed in larvae, with resistance factors of
      94-fold and 1350-fold at the IC50 and IC95, respectively, in larval development
      assays after nine generations of selection. There was some cross-resistance to
      bephenium (70-fold increase in IC95). The expression of all the putative subunit
      components of levamisole-sensitive nAChRs, as well as a number of ancillary
      protein genes, particularly Hco-unc-29.1 and -ric-3, were significantly decreased
      (up to 5.5-fold) in the resistant larvae at generation nine compared to the
      starting population. However, adult worms did not show any resistance to
      levamisole, and showed an inverse pattern of gene expression changes, with many
      target site genes showing increased expression compared to the starting
      population. A comparison of the larval/adult drug sensitivity data with the known
      relationships for field-derived isolates indicated that the adults of our
      selected population should have been highly resistant to the drug if the
      larval/adult sensitivity relationships were in accordance with previous field
      isolates. Hence, our selected worms showed a life-stage drug sensitivity pattern
      quite different to that seen in the field. The present study has highlighted an
      association between drug target site changes and resistance to levamisole in H.
      contortus larvae. However, it has also highlighted the artificial nature of the
      larval selection method with levamisole, as the resistance phenotype and the
      associated molecular changes were only observed in the drug-pressured life stage.
      The study therefore reinforces the need for caution in extrapolating larval-based
      laboratory selection outcomes to field resistances. 

PMID- 25983233
TI  - Mechanisms for overestimating acute myocardial infarct size with gadolinium
      enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and
      kinetic study.
AB  - AIMS: It remains controversial whether cardiovascular magnetic resonance imaging
      with gadolinium only enhances acutely infarcted or also salvaged myocardium. We
      hypothesized that enhancement of salvaged myocardium may be due to altered
      extracellular volume (ECV) and contrast kinetics compared with normal and
      infarcted myocardium. If so, these mechanisms could contribute to overestimation
      of acute myocardial infarction (AMI) size. METHODS AND RESULTS: Imaging was
      performed at 1.5T <= 7 days after AMI with serial T1 mapping and volumetric early
      (5 min post-contrast) and late (20 min post-contrast) gadolinium enhancement
      imaging. Infarcts were classified as transmural (>75% transmural extent) or non
      transmural. Patients with non-transmural infarctions (n = 15) had shorter
      duration of symptoms before reperfusion (P = 0.02), lower peak troponin (P =
      0.008), and less microvascular obstruction (P < 0.001) than patients with
      transmural infarcts (n = 22). The size of enhancement at 5 min was greater than
      at 20 min (18.7 +/- 12.7 vs. 12.1 +/- 7.0%, P = 0.003) in non-transmural
      infarctions, but similar in transmural infarctions (23.0 +/- 10.0 vs. 21.9 +/-
      9.9%, P = 0.21). ECV of salvaged myocardium was greater than normal (39.5 +/- 5.8
      vs. 24.1 +/- 3.1%) but less than infarcted myocardium (50.5 +/- 6.0%, both P <
      0.001). In kinetic studies of non-transmural infarctions, salvaged and infarcted
      myocardium had similar T1 at 4 min but different T1 at 8-20 min post-contrast.
      CONCLUSION: The extent of gadolinium enhancement in AMI is modulated by ECV and
      contrast kinetics. Image acquisition too early after contrast administration
      resulted in overestimation of infarct size in non-transmural infarctions due to
      enhancement of salvaged myocardium.

PMID- 25983234
TI  - Cleavable ester-linked magnetic nanoparticles for labeling of solvent-exposed
      primary amine groups of peptides/proteins.
AB  - To study the solvent-exposed lysine residues of peptides/proteins, we previously
      reported disulfide-linked N-hydroxysuccinimide ester-modified silica-coated iron
      oxide magnetic nanoparticles (NHS-SS-SiO2@Fe3O4 MNPs). The presence of a
      disulfide bond in the linker limits the use of disulfide reducing agent during
      protein digestion and allows unwanted disulfide formation between the MNPs and
      protein. In the current work, the disulfide bond was replaced with a cleavable
      ester group to synthesize NHS ester-modified SiO2@Fe3O4 MNPs. Use of the
      cleavable ester group provides an improved method for protein labeling and allows
      the use of disulfide reducing agents during protein digestion. 

PMID- 25983235
TI  - Predicting the right spacing between protein immobilization sites on self
      assembled monolayers to optimize ligand binding.
AB  - Self-assembled monolayers designed to immobilize capture antibodies are usually
      prepared using a mixture of functional and inactive linkers. Here, using low
      molar ratios (1:1 to 1:100) of the two linkers resulted in loss of binding
      capability of the anti-EGFR (epidermal growth factor receptor) antibody
      nimotuzumab, as assessed by surface plasmon resonance imaging. We then developed
      a simple theoretical model to predict the optimal surface density of the
      functional linker, taking into account the antibody size and linker diameter. A
      high (1:1000) dilution of the functional linker yielded the best results. As an
      advantage, this approach does not require chemical modification of the protein. 

PMID- 25983236
TI  - Optimization of human dendritic cell sample preparation for mass spectrometry
      based proteomic studies.
AB  - Dendritic cells (DCs) are specialized leukocytes that orchestrate the adaptive
      immune response. Mass spectrometry (MS)-based proteomic study of these cells
      presents technical challenges, especially when the DCs are human in origin due to
      the paucity of available biological material. Here, to maximize MS coverage of
      the global human DC proteome, different cell disruption methods, lysis
      conditions, protein precipitation, and protein pellet solubilization and
      denaturation methods were compared. Mechanical disruption of DC cell pellets
      under cryogenic conditions, coupled with the use of RIPA
      (radioimmunoprecipitation assay) buffer, was shown to be the method of choice
      based on total protein extraction and on the solubilization and identification of
      nuclear proteins. Precipitation by acetone was found to be more efficient than
      that by 10% trichloroacetic acid (TCA)/acetone, allowing in excess of 28% more
      protein identifications. Although being an effective strategy to eliminate the
      detergent residue, the acetone wash step caused a loss of protein
      identifications. However, this potential drawback was overcome by adding 1%
      sodium deoxycholate into the dissolution buffer, which enhanced both solubility
      of the precipitated proteins and digestion efficiency. This in turn resulted in 6
      to 11% more distinct peptides and 14 to 19% more total proteins identified than
      using 0.5M triethylammonium bicarbonate alone, with the greatest increase (34%)
      for hydrophobic proteins. 

PMID- 25983238
TI  - Joint position sense error in people with neck pain: A systematic review.
AB  - BACKGROUND: Several studies in recent decades have examined the relationship
      between proprioceptive deficits and neck pain. However, there is no uniform
      conclusion on the relationship between the two. Clinically, proprioception is
      evaluated using the Joint Position Sense Error (JPSE), which reflects a person's
      ability to accurately return his head to a predefined target after a cervical
      movement. OBJECTIVES: We focused to differentiate between JPSE in people with
      neck pain compared to healthy controls. STUDY DESIGN: Systematic review according
      to the PRISMA guidelines. METHOD: Our data sources were Embase, Medline OvidSP,
      Web of Science, Cochrane Central, CINAHL and Pubmed Publisher. To be included,
      studies had to compare JPSE of the neck (O) in people with neck pain (P) with
      JPSE of the neck in healthy controls (C). RESULTS/FINDINGS: Fourteen studies were
      included. Four studies reported that participants with traumatic neck pain had a
      significantly higher JPSE than healthy controls. Of the eight studies involving
      people with non-traumatic neck pain, four reported significant differences
      between the groups. The JPSE did not vary between neck-pain groups. CONCLUSIONS:
      Current literature shows the JPSE to be a relevant measure when it is used
      correctly. All studies which calculated the JPSE over at least six trials showed
      a significantly increased JPSE in the neck pain group. This strongly suggests
      that 'number of repetitions' is a major element in correctly performing the JPSE
      test.

PMID- 25983239
TI  - Interventional radiology residency: steps to implementation.
AB  - Implementation of an interventional radiology (IR) residency program requires
      significant planning, as well as clear communication and consensus among
      departmental and institutional stakeholders. The goal of this short article is to
      highlight key decisions and steps that are needed to launch an IR residency, and
      to illustrate a possible timeline for implementation of the integrated and
      independent IR residency models. 

PMID- 25983237
TI  - Efficacy of 'Tailored Physical Activity' on reducing sickness absence among
      health care workers: A 3-months randomised controlled trial.
AB  - AIM: The aim was to evaluate efficacy of "Tailored Physical Activity" (TPA)
      versus a reference group (REF) in reducing the number of self-reported days of
      sickness absence for health care workers in the Sonderborg Municipality. METHODS:
      In this randomised controlled trial, all participants (n = 54) received health
      guidance for 1.5 h and were randomised to TPA or REF. The primary aim was to make
      a comparison of participants' self-reported sickness absence due to
      musculoskeletal troubles measured three months after baseline. Secondary outcomes
      included anthropometric, health-related and physical capacity measures. RESULTS:
      A TPA intervention was not significantly more effective than REF in reducing
      sickness absence caused by musculoskeletal troubles. However, there were
      significant improvements for TPA participants compared to REF in reducing pain
      intensity from 47.9 mm to 21.8 mm (p < .01), increasing work ability from 7.3 to
      8.1 (p = .04) and decreasing kinesiophobia from 26.7 to 22.5 (p < .01). A trend
      towards a significant improvement was seen for aerobic capacity while no effect
      of the intervention was found on productivity, BMI or grip strength. CONCLUSION:
      This physical activity intervention is a promising initiative for health care
      workers since participants achieved a substantial effect on their experience of
      pain, on their work ability and on their fear of physical movement relating to
      pain. Moreover, a difference in aerobic capacity was apparent between the sample
      groups. TPA however, had no significant effect in reducing sickness absence days.

PMID- 25983240
TI  - Clinician and Radiologist: A Time for Realignment.

PMID- 25983241
TI  - Variations in single/two stage thyroidectomies for cancer may be due to
      differences in thyroid fine needle cytology provision.
AB  - BACKGROUND & AIMS: Recommended treatment for thyroid cancers >10 mm is single
      stage total thyroidectomy (SST). Cancers diagnosed by diagnostic lobectomy may
      need completion surgery resulting in two stage thyroidectomies (TST). We noticed
      significant variation in numbers of SST and TST between hospitals within our
      cancer network and explored reasons for this using a prospective database
      containing all cases from 2004 to 2011 (n = 1030). We therefore conducted a
      survey of thyroid cytology provision across the network during 2010-2011.
      METHODS: A central university hospital with the largest caseload (21.5% of total)
      was chosen as "benchmark". Of 14 remaining hospitals 3 were excluded from
      analysis due to low thyroid operation numbers and the remaining compared with
      benchmark. We used individual chi-squared tests with Bonferroni correction to
      explore variation in expected and observed numbers of SST/TST. Analysis of
      variance (ANOVA) was used to examine reasons for observed differences. RESULTS:
      Significant variance in SST/TST was seen between hospitals (p < 0.00001). Three
      hospitals had frequencies of SST statistically similar to reference hospital;
      each reported 201-300 thyroid cytology cases during the survey period. The
      remaining 8 had lower rates of SST, the 2 lowest performing hospitals having SST
      rates of 11% (p = 0.0004) and 9% (p < 0.0001). These eight hospitals reported
      fewer than 200 cytology cases each, shared amongst 4-7 pathologists per site.
      Differences were unrelated to patient age, gender, tumour histology or stage
      (ANOVA). Only the reference hospital had specialist cytopathologists. CONCLUSION:
      Variation in thyroid cytology provision may increase TST rates. Thyroid cytology
      should be concentrated in high volume centres with specialist thyroid
      cytopathologists.

PMID- 25983242
TI  - Previously identified patellar tendinopathy risk factors differ between elite and
      sub-elite volleyball players.
AB  - Patellar tendinopathy is the most common knee injury incurred in volleyball, with
      its prevalence in elite athletes more than three times that of their sub-elite
      counterparts. The purpose of this study was to determine whether patellar
      tendinopathy risk factors differed between elite and sub-elite male volleyball
      players. Nine elite and nine sub-elite male volleyball players performed a
      lateral stop-jump block movement. Maximum vertical jump, training history, muscle
      extensibility and strength, three-dimensional landing kinematics (250 Hz), along
      with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon
      loading were collected during each trial. Multivariate analyses of variance (P <
      0.05) assessed for between-group differences in risk factors or patellar tendon
      loading. Significant interaction effects were further evaluated using post-hoc
      univariate analysis of variance tests. Landing kinematics, neuromuscular
      activation patterns, patellar tendon loading, and most of the previously
      identified risk factors did not differ between the elite and sub-elite players.
      However, elite players participated in a higher training volume and had less
      quadriceps extensibility than sub-elite players. Therefore, high training volume
      is likely the primary contributor to the injury discrepancy between elite and sub
      elite volleyball players. Interventions designed to reduce landing frequency and
      improve quadriceps extensibility are recommended to reduce patellar tendinopathy
      prevalence in volleyball players.

PMID- 25983244
TI  - Comprehensively evaluating cis-regulatory variation in the human prostate
      transcriptome by using gene-level allele-specific expression.
AB  - The identification of cis-acting regulatory variation in primary tissues has the
      potential to elucidate the genetic basis of complex traits and further our
      understanding of transcriptomic diversity across cell types. Expression
      quantitative trait locus (eQTL) association analysis using RNA sequencing (RNA
      seq) data can improve upon the detection of cis-acting regulatory variation by
      leveraging allele-specific expression (ASE) patterns in association analysis.
      Here, we present a comprehensive evaluation of cis-acting eQTLs by analyzing RNA
      seq gene-expression data and genome-wide high-density genotypes from 471 samples
      of normal primary prostate tissue. Using statistical models that integrate ASE
      information, we identified extensive cis-eQTLs across the prostate transcriptome
      and found that approximately 70% of expressed genes corresponded to a significant
      eQTL at a gene-level false-discovery rate of 0.05. Overall, cis-eQTLs were
      heavily concentrated near the transcription start and stop sites of affected
      genes, and effects were negatively correlated with distance. We identified
      multiple instances of cis-acting co-regulation by using phased genotype data and
      discovered 233 SNPs as the most strongly associated eQTLs for more than one gene.
      We also noted significant enrichment (25/50, p = 2E-5) of previously reported
      prostate cancer risk SNPs in prostate eQTLs. Our results illustrate the benefit
      of assessing ASE data in cis-eQTL analyses by showing better reproducibility of
      prior eQTL findings than of eQTL mapping based on total expression alone.
      Altogether, our analysis provides extensive functional context of thousands of
      SNPs in prostate tissue, and these results will be of critical value in guiding
      studies examining disease of the human prostate.

PMID- 25983243
TI  - A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia.
AB  - Myoclonus-dystonia (M-D) is a rare movement disorder characterized by a
      combination of non-epileptic myoclonic jerks and dystonia. SGCE mutations
      represent a major cause for familial M-D being responsible for 30%-50% of cases.
      After excluding SGCE mutations, we identified through a combination of linkage
      analysis and whole-exome sequencing KCTD17 c.434 G>A p.(Arg145His) as the only
      segregating variant in a dominant British pedigree with seven subjects affected
      by M-D. A subsequent screening in a cohort of M-D cases without mutations in SGCE
      revealed the same KCTD17 variant in a German family. The clinical presentation of
      the KCTD17-mutated cases was distinct from the phenotype usually observed in M-D
      due to SGCE mutations. All cases initially presented with mild myoclonus
      affecting the upper limbs. Dystonia showed a progressive course, with increasing
      severity of symptoms and spreading from the cranio-cervical region to other
      sites. KCTD17 is abundantly expressed in all brain regions with the highest
      expression in the putamen. Weighted gene co-expression network analysis, based on
      mRNA expression profile of brain samples from neuropathologically healthy
      individuals, showed that KCTD17 is part of a putamen gene network, which is
      significantly enriched for dystonia genes. Functional annotation of the network
      showed an over-representation of genes involved in post-synaptic dopaminergic
      transmission. Functional studies in mutation bearing fibroblasts demonstrated
      abnormalities in endoplasmic reticulum-dependent calcium signaling. In
      conclusion, we demonstrate that the KCTD17 c.434 G>A p.(Arg145His) mutation
      causes autosomal dominant M-D. Further functional studies are warranted to
      further characterize the nature of KCTD17 contribution to the molecular
      pathogenesis of M-D.

PMID- 25983245
TI  - Biallelic mutations in the autophagy regulator DRAM2 cause retinal dystrophy with
      early macular involvement.
AB  - Retinal dystrophies are an overlapping group of genetically heterogeneous
      conditions resulting from mutations in more than 250 genes. Here we describe five
      families affected by an adult-onset retinal dystrophy with early macular
      involvement and associated central visual loss in the third or fourth decade of
      life. Affected individuals were found to harbor disease-causing variants in DRAM2
      (DNA-damage regulated autophagy modulator protein 2). Homozygosity mapping and
      exome sequencing in a large, consanguineous British family of Pakistani origin
      revealed a homozygous frameshift variant (c.140delG [p.Gly47Valfs(*)3]) in nine
      affected family members. Sanger sequencing of DRAM2 in 322 unrelated probands
      with retinal dystrophy revealed one European subject with compound heterozygous
      DRAM2 changes (c.494G>A [p.Trp165(*)] and c.131G>A [p.Ser44Asn]). Inspection of
      previously generated exome sequencing data in unsolved retinal dystrophy cases
      identified a homozygous variant in an individual of Indian origin (c.64_66del
      [p.Ala22del]). Independently, a gene-based case-control association study was
      conducted via an exome sequencing dataset of 18 phenotypically similar case
      subjects and 1,917 control subjects. Using a recessive model and a binomial test
      for rare, presumed biallelic, variants, we found DRAM2 to be the most
      statistically enriched gene; one subject was a homozygote (c.362A>T
      [p.His121Leu]) and another a compound heterozygote (c.79T>C [p.Tyr27His] and
      c.217_225del [p.Val73_Tyr75del]). DRAM2 encodes a transmembrane lysosomal protein
      thought to play a role in the initiation of autophagy. Immunohistochemical
      analysis showed DRAM2 localization to photoreceptor inner segments and to the
      apical surface of retinal pigment epithelial cells where it might be involved in
      the process of photoreceptor renewal and recycling to preserve visual function.

PMID- 25983247
TI  - Cough reduction using capsaicin: An alternative mechanistic hypothesis.

PMID- 25983246
TI  - Concurrent whole-genome haplotyping and copy-number profiling of single cells.
AB  - Methods for haplotyping and DNA copy-number typing of single cells are paramount
      for studying genomic heterogeneity and enabling genetic diagnosis. Before
      analyzing the DNA of a single cell by microarray or next-generation sequencing, a
      whole-genome amplification (WGA) process is required, but it substantially
      distorts the frequency and composition of the cell's alleles. As a consequence,
      haplotyping methods suffer from error-prone discrete SNP genotypes (AA, AB, BB)
      and DNA copy-number profiling remains difficult because true DNA copy-number
      aberrations have to be discriminated from WGA artifacts. Here, we developed a
      single-cell genome analysis method that reconstructs genome-wide haplotype
      architectures as well as the copy-number and segregational origin of those
      haplotypes by employing phased parental genotypes and deciphering WGA-distorted
      SNP B-allele fractions via a process we coin haplarithmisis. We demonstrate that
      the method can be applied as a generic method for preimplantation genetic
      diagnosis on single cells biopsied from human embryos, enabling diagnosis of
      disease alleles genome wide as well as numerical and structural chromosomal
      anomalies. Moreover, meiotic segregation errors can be distinguished from mitotic
      ones.

PMID- 25983248
TI  - Fixed ratio or lower limit of normal as cut-off value for FEV1/VC: Response to
      the letter by Vaz Fragoso et al.

PMID- 25983249
TI  - Preserving the pulmonary valve during early repair of tetralogy of Fallot:
      Anatomic substrates and surgical strategies.
AB  - OBJECTIVE: To describe the anatomy of the PV in tetralogy of Fallot (TOF) and to
      define the influence of PV anatomy on the development of surgical techniques for
      PV preservation during early repair. METHODS: The PV was evaluated in 79 anatomic
      specimens of patients with TOF who had not undergone surgery for repair, and in
      82 patients who underwent early TOF repair at our institution. New surgical
      techniques for PV preservation during early repair are described. RESULTS: The PV
      in TOF was predominantly bicuspid (n = 118 of 160; 73.7%), less frequently
      tricuspid (n = 28 of 160; 17.5%), and seldom unicuspid (n = 14 of 160; 8.8%). In
      82 cases (51.3%), the PV cusps were normal; in 78 cases (48.7%), they were
      thickened and dysplastic. Preservation of the PV was possible in 46 of 82 (56%)
      consecutive patients during TOF repair in our more recent experience, either
      using balloon dilation alone (18 of 46; 39%) or in association with other PV
      plasty procedures (28 of 46; 61%). Most bicuspid and tricuspid valves were
      salvageable, but unicuspid valves were not suitable. After a median follow-up
      time of 2.8 years (range, 0.5-6.8 years), the degree of PV regurgitation
      continued to be zero or mild in 40 patients (86%), and moderate in 6 (14%).
      CONCLUSIONS: The majority of patients with TOF (>90%) have a bicuspid or
      tricuspid PV, which is the most favorable surgical anatomy for preserving the PV,
      independent of the degree of leaflet dysplasia. The recent introduction of more
      complex PV plasty techniques, such as delamination plasty, allowed us to further
      extend the applicability of PV-preservation techniques.

PMID- 25983250
TI  - The ongoing quest for an ideal surgical repair for tetralogy of Fallot: Focus on
      the pulmonary valve.

PMID- 25983251
TI  - Why are patients being readmitted after surgery for esophageal cancer?
AB  - OBJECTIVE: Readmission after surgery is an unwanted adverse event that is costly
      to the healthcare system. We sought to evaluate factors associated with increased
      risk of readmission and to characterize the nature of these readmissions in
      patients who have esophageal cancer. METHODS: A retrospective cohort study was
      performed in 306 patients with esophageal carcinoma who underwent neoadjuvant
      chemoradiation followed by esophagectomy at Johns Hopkins Hospital between 1993
      and 2011. Logistic regression was used to identify factors associated with 30-day
      readmission. Readmissions were defined as inpatient admissions to our institution
      within 30 days of discharge. RESULTS: The median age at surgery was 61 years; the
      median postoperative length of stay was 9 days; and 48% of patients had >=1
      postoperative complication (POC). The 30-day readmission rate was 13.7% (42 of
      306). In univariate analysis, length of stay and having >=1 POC were
      significantly associated with readmission. In multivariate analysis, having >=1
      POC was significantly associated with a >2-fold increase in risk for 30-day
      readmission (odds ratio 2.35, with 95% confidence interval [1.08-5.09], P = .031)
      when controlling for age at diagnosis and length of stay. Of the 42 patients who
      were readmitted, 67% experienced POCs after surgery; 50% of patients who
      experienced POCs were readmitted for reasons related to their postoperative
      complication. The most common reasons for readmission were pulmonary issues
      (29%), anastomotic complications (20%), gastrointestinal concerns (17%), and
      venous thromboembolism (14%). CONCLUSIONS: Complications not adequately managed
      before discharge may lead to readmission. Quality improvement efforts surrounding
      venous thromboembolism prophylaxis, and discharging patients nothing-by-mouth,
      may be warranted.

PMID- 25983253
TI  - Cardiovascular surgery outcomes of patients with human immunodeficiency virus
      infection: New data in the era of combination antiretroviral therapy.

PMID- 25983254
TI  - Cardiovascular surgery outcomes of patients with HIV: New data in the era of
      combination antiretroviral therapy.

PMID- 25983255
TI  - The case for multiple arterial coronary artery bypass graft: No longer a leap of
      faith.

PMID- 25983256
TI  - The Ross procedure: Underuse or under-comprehension?

PMID- 25983257
TI  - Treatment of hemolysis with intravenous unfractionated heparin using an
      antifactor Xa-based monitoring protocol.

PMID- 25983258
TI  - Fibrinogen concentrate as first-line therapy in children undergoing cardiac
      surgery: Promising perspectives.

PMID- 25983259
TI  - Computed tomography or chest radiograph surveillance following stage I non-small
      cell lung cancer resection?

PMID- 25983260
TI  - Closing the stable door before the horse leaves.

PMID- 25983261
TI  - Malignant pericardial effusion: Different therapeutic perspectives.

PMID- 25983263
TI  - Role of EGFR mutations in lung cancers: prognosis and tumor chemosensitivity.
AB  - Lung cancers with an epidermal growth factor receptor (EGFR) gene mutation
      account for ~40 % of adenocarcinomas in East Asians and ~15 % of those in
      Caucasians and African Americans, which makes them one of the most common
      molecularly defined lung cancer subsets. The discriminative clinical and
      pathological features of lung cancers with EGFR mutations have been intensively
      studied, and the predictive role of an EGFR mutation for treatment with EGFR
      tyrosine kinase inhibitors (EGFR-TKIs) is well established. However,
      controversial issues remain regarding the clinical and therapeutic implications
      of EGFR mutations in lung cancers. These include the prognostic impact of the
      EGFR mutation, its predictive implication for successful treatment with
      anticancer agents other than EGFR-TKIs, appropriate cytotoxic agents for lung
      cancers with this mutation, and the chemosensitivity of EGFR-mutation-positive
      lung cancers after acquisition of resistance to EGFR-TKIs. In this review, we
      discuss these unanswered but important questions, referring to in vitro studies,
      basic research, retrospective analyses, and the results of phase III clinical
      trials. 

PMID- 25983265
TI  - Ferulic acid inhibits UVB-radiation induced photocarcinogenesis through
      modulating inflammatory and apoptotic signaling in Swiss albino mice.
AB  - The aim of this study was to evaluate the photochemopreventive effects of ferulic
      acid (FA) against chronic ultraviolet-B (290-320 nm) induced oxidative stress,
      inflammation and angiogenesis in the skin of Swiss albino mice. Chronic UVB
      exposure (180 mJ/cm(2) for 30 weeks; thrice in a week) induced tumor formation in
      the mice skin that showed increased expression of carcinogenic and inflammatory
      markers when compared with the control animals. The intraperitoneal (FAIP) and
      topical (FAT) administration of FA significantly reduced the incidence of UVB
      induced tumor volume and tumor weight in the mice skin. Histopathological studies
      revealed that both FAIP and FAT administration prevented the UVB-induced
      hyperplasia, squamous cell carcinoma (SCC) and dysplastic feature in the mice
      skin. Further, it has been observed that FA treatment reverted chronic UVB
      induced oxidative damage (thiobarbituric acid reactive substances, superoxide
      dismutase, catalase, glutathione peroxidase) accompanied with modulation of
      vascular endothelial growth factor (VEGF), inducible nitric oxide synthase
      (iNOS), TNF-alpha and IL-6 in the mice skin tumor. FA treatment also modulates
      mutated p53, Bcl-2 and Bax expressions in the UVB-induced mice skin tumor. Thus,
      the results of the present study indicate ferulic acid has potential against UVB
      induced carcinogenesis in the Swiss albino mice. 

PMID- 25983264
TI  - Sodium tungstate induced neurological alterations in rat brain regions and their
      response to antioxidants.
AB  - Tungsten, recognized recently as an environmental contaminant, is being used in
      arms and ammunitions as substitute to depleted uranium. We studied the effects of
      sodium tungstate on oxidative stress, few selected neurological variables like
      acetylcholinesterase, biogenic amines in rat brain regions (cerebral cortex,
      hippocampus and cerebellum) and their prevention following co-administration of N
      acetylcysteine (NAC), naringenin and quercetin. Animals were sub-chronically
      exposed to sodium tungstate (100 ppm in drinking water) and orally co
      supplemented with different antioxidants (0.30 mM) for three months. Sodium
      tungstate significantly decreased the activity of acetylcholinesterase, dopamine,
      nor-epinephrine and 5-hydroxytryptamine levels while it increased monoamine
      oxidase activity in different brain regions. Tungstate exposure produced a
      significant increase in biochemical variables indicative of oxidative stress
      while, neurological alterations were more pronounced in the cerebral cortex
      compared to other regions. Co-administration of NAC and flavonoids with sodium
      tungstate significantly restored glutathione, prevented changes in the brain
      biogenic amines, reactive oxygen species (ROS) and TBARS levels in the different
      brain regions. The protection was more prominent in the animals co-administered
      with NAC. We can thus conclude that sodium tungstate induced brain oxidative
      stress and the alterations in some neurological variables can effectively be
      reduced by co-supplementation of NAC. 

PMID- 25983266
TI  - Unstable Cervical Spine Fracture with Normal Computed Tomography Imaging.

PMID- 25983262
TI  - Translational biomarkers of acetaminophen-induced acute liver injury.
AB  - Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver
      injury, liver necrosis and liver failure. APAP-induced liver injury is associated
      with glutathione depletion, the formation of APAP protein adducts, the generation
      of reactive oxygen and nitrogen species and mitochondrial injury. The systems
      biology omics technologies (transcriptomics, proteomics and metabolomics) have
      been used to discover potential translational biomarkers of liver injury. The
      following review provides a summary of the systems biology discovery process,
      analytical validation of biomarkers and translation of omics biomarkers from the
      nonclinical to clinical setting in APAP-induced liver injury. 

PMID- 25983267
TI  - Severe poisoning after self-reported use of 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2
      methoxyphenyl)methyl]ethanamine, a novel substituted amphetamine: a case series.
AB  - Significant toxicity from amphetamine and cathinone derivatives is being
      increasingly reported. We describe a series of self-reported exposures to 2-(4
      iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25-I-NBOME or 25
      I), a novel amphetamine derivative. Ten patients with an average age of 17 years
      presented to local emergency departments (EDs) in our community after ingestion
      and/or insufflation of a drug referred to as "25-I." Of 10 patients, 6 reported
      taking 25-I alone; other substances included ethanol; 2,5-dimethoxy-4
      ethylphenethylamine; marijuana; and ketamine. Most common effects included
      tachycardia (90%), hypertension (70%), agitation (60%), and hallucinations (50%).
      The average heart rate was 123 beats per minute. Two patients were found in
      status epilepticus, and another was found unresponsive. One patient who had a
      seizure had multiple, discrete intraparenchymal hemorrhages and acute kidney
      injury. Six patients were admitted to the intensive care unit, two were treated
      in the ED and released, and 1 each was admitted to psychiatry or managed in a
      clinical decision unit and subsequently discharged. Three patients required
      emergent intubation, and all admitted patients (7/10) were given intravenous
      benzodiazepines for sedation. Urine and blood specimens were obtained from 1
      patient, which showed analytic confirmation of 25-I. In addition to
      sympathomimetic effects, methoxy and other substituent groups impart serotonergic
      effects, resulting in hallucinogenic properties. 2-(4-iodo-2,5-dimethoxyphenyl)-N
      [(2-methoxyphenyl)methyl]ethanamine appears to be extremely potent with a
      reported "dose" of 500 MUg resulting in increased potential for inadvertent
      overdose. This case series describes significant morbidity in a local cluster of
      young patients after self-reported use of 25-I, a newly identified drug of abuse.

PMID- 25983268
TI  - Frequency of ED revisits and death among older adults after a fall.
AB  - INTRODUCTION: Falls among older adults (aged >=65 years) are the leading cause of
      both injury deaths and emergency department (ED) visits for trauma. We examine
      the characteristics and prevalence of older adult ED fallers as well as the
      recurrent ED visit and mortality rate. METHODS: This was a retrospective analysis
      of a cohort of elderly fall patients who presented to the ED between 2005 and
      2011 of 2 urban, level 1 trauma, teaching hospitals with approximately 80000 to
      95000 annual visits. We examined the frequency of ED revisits and death at 3
      days, 7 days, 30 days, and 1 year controlling for certain covariates. RESULTS:
      Our cohort included 21340 patients. The average age was 78.6 years. An increasing
      proportion of patients revisited the ED over the course of 1 year, ranging from
      2% of patients at 3 days to 25% at 1 year. Death rates increased from 1.2% at 3
      days to 15% at 1 year. A total of 10728 patients (50.2%) returned to the ED at
      some point during our 7-year study period, and 36% of patients had an ED revisit
      or death within 1 year. In multivariate logistic regression, male sex and
      comorbidities were associated with ED revisits and death. CONCLUSION: More than
      one-third of older adult ED fall patients had an ED revisit or died within 1
      year. Falls are one of the geriatric syndromes that contribute to frequent ED
      revisits and death rates. Future research should determine whether falls increase
      the risk of such outcomes and how to prevent future fall and death.

PMID- 25983269
TI  - Codeine: An Under-Recognized and Easily Treated Cause of Acute Abdominal Pain.
AB  - We present 2 cases of acute abdominal pain secondary to oral codeine that
      resolved after the administration of intravenous naloxone.

PMID- 25983270
TI  - Modified shock index is a predictor for 7-day outcomes in patients with STEMI.
AB  - SUBJECT: The aim of this study was to compare the predictive values of modified
      shock index (MSI) and shock index (SI) for 7-day outcome in patients with ST
      segment elevation myocardial infarction (STEMI). METHODS: This retrospective
      study included 160 consecutive patients with STEMI and emergency percutaneous
      coronary intervention. The blood pressure (BP) and heart rate (HR) measured at
      emergency department were used to calculate SI (HR/systolic BP) and MSI (HR/mean
      artery pressure). The major adverse cardiac events (MACE) included all-cause
      mortality, life-threatening arrhythmias, cardiogenic shock, and Killip class
      within 7 days. RESULTS: Forty-nine patients had increased MSI (>=1.4), whereas 72
      had increased SI (>=0.7). Except the parameters on BP and HR, other parameters
      were similar between the normal and increased SI groups. However, the increased
      MSI group had significantly higher age (69.0 +/- 13.0 years vs 63.9 +/- 12.9
      years, P = .025) than the normal MSI group. The 7-day all-cause mortality was
      8.8%, and MACE rate was 24.4% in this study. Both increased SI and increased MSI
      predicted higher MACE rates. However, the odds ratios of increased MSI for all
      cause mortality (6.8 vs 3.4), cardiogenic shock (3.0 vs 1.6), life-threatening
      arrhythmias (9.1 vs 4.6), and MACE (6.8 vs 3.4) were higher than those of
      increased SI. Modified shock index and SI were independent factor for MACE, but
      the odds ratio of MSI was higher than of SI (3.05 vs 1.07). CONCLUSIONS: Both SI
      and MSI in emergency department could predict the all-cause mortality and MACE
      rates within 7 days in patients with STEMI, but MSI may be more accurate than SI.

PMID- 25983271
TI  - Facial nerve palsy in a 3-year-old child with severe hypertension.
AB  - We report an interesting case of a child with new-onset malignant hypertension
      (HTN) associated with facial paralysis. A review of the medical literature on
      this association and discussion of diagnostic and management aspects are
      included.

PMID- 25983272
TI  - Recurrent hypoglycemia in a toddler.
AB  - Idiopathic ketotic hypoglycemia is the most common cause of hypoglycemia in
      toddlers. This diagnosis should be considered in any hypoglycemic toddler with no
      prior history of abnormal growth who is developmentally normal when toxic
      ingestions and sepsis are inconsistent with the clinical picture. Diagnosis is
      important in preventing serious long-term sequelae and is made in the setting of
      hypoglycemia, ketonuria, and ketonemia. Therefore, checking urine and blood
      ketones is an essential part of the evaluation in any hypoglycemic toddler. We
      report the case of a 3-year-old girl with recurrent hypoglycemia secondary to
      idiopathic ketotic hypoglycemia.

PMID- 25983273
TI  - Isolation and expression of HMG-CoA synthase and HMG-CoA reductase genes in
      different development stages, tissues and treatments of the Chinese white pine
      beetle, Dendroctonus armandi (Curculionidae: Scolytinae).
AB  - We isolated two full-length cDNAs encoding 3-hydroxy-3-methyl-glutaryl coenzyme A
      synthase (HMG-S) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R) from
      the Chinese white pine beetle (Dendroctonus armandi), and carried out some
      bioinformatic analysis on the full-length nucleic acid sequences and deduced
      amino acid sequences. Differential expression of the DaHMG-S and DaHMG-R genes
      was observed between sexes (emerged adults), and within these significant
      differences among development stage, tissue distribution, fed on phloem of Pinus
      armandi and topically applied juvenile hormone (JH) III. Increase of DaHMG-S and
      DaHMG-R mRNA levels in males suggested that they may play a role in mevalonate
      pathway. Information from the present study might contribute to understanding the
      relationship between D. armandi and its semiochemical production. 

PMID- 25983274
TI  - Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and
      attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats.
AB  - Activation of the peripheral angiotensin-(1-7)/Mas axis of the renin-angiotensin
      system produces important cardioprotective actions, counterbalancing the
      deleterious actions of an overactivity of Ang II/AT1 axis. In the present study
      we evaluated whether the chronic increase in Ang-(1-7) levels in the brain could
      ameliorate cardiac disorders observed in transgenic (mRen2)27 hypertensive rats
      through actions on Mas receptor. Sprague Dawley (SD) and transgenic (mRen2)27
      hypertensive rats, instrumented with telemetry probe for arterial pressure (AP)
      measurement were subjected to 14 days of ICV infusion of Ang-(1-7) (200 ng/h) or
      Ang-(1-7) associated with Mas receptor antagonist (A779, 1 MUg/h) or 0.9% sterile
      saline (0.5 MUl/h) through osmotic mini-pumps. Ang-(1-7) infusion in (mRen2)27
      rats reduced blood pressure, normalized the baroreflex control of HR, restored
      cardiac autonomic balance, reduced cardiac hypertrophy and pre-fibrotic
      alterations and decreased the altered imbalance of Ang II/Ang-(1-7) in the heart.
      In addition, there was an attenuation of the increased levels of atrial
      natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF
      beta in the heart of (mRen2)27 rats. Furthermore, most of these effects were
      mediated in the brain by Mas receptor, since were blocked by its selective
      antagonist, A779. These data indicate that increasing Ang-(1-7) levels in the
      brain can attenuate cardiovascular disorders observed in (mRen2)27 hypertensive
      rats, probably by improving the autonomic balance to the heart due to centrally
      mediated actions on Mas receptor. 

PMID- 25983275
TI  - alpha-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF
      kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse
      model of Parkinson's disease.
AB  - The selective loss of dopaminergic neurons in Parkinson's disease (PD) is
      associated with microglial activation. Therefore, the importance of early
      therapeutic intervention to inhibit microglial activation would be an effective
      strategy to alleviate the progression of PD. alpha-Asarone, an active compound
      found in Araceae and Annonaceae plant species has been used to improve various
      disease conditions including central nervous system disorders. In the present
      study the in vitro and in vivo therapeutic effects of alpha-asarone isolated from
      the rhizome of Acorus gramineus Solander was evaluated on microglia-mediated
      neuroinflammation and neuroprotection. Lipopolysaccharide (LPS)-stimulated BV-2
      microglial cells were used to evaluate in vitro effects. 1-methyl-4 phenyl-1, 2,
      3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD was developed to study
      the neuroprotective effects of alpha-asarone in vivo. The results indicated that
      alpha-asarone significantly attenuated the LPS-stimulated increase in
      neuroinflammatory responses and suppressed pro-inflammatory cytokine production
      in BV-2 cells. Mechanistic study revealed that alpha-asarone inhibited the LPS
      stimulated activation via regulation of nuclear factor kappa-B by blocking
      degradation of inhibitor kappa B-alpha signaling in BV-2 microglial cells. In in
      vivo studies, MPTP intoxication to mice resulted in brain microglial activation
      and significant behavioral deficits. Prophylactic treatment with alpha-asarone
      suppressed microglial activation and attenuated PD-like behavioral impairments as
      assessed by the Y-maze and pole tests. Taken together, these data demonstrate
      that alpha-asarone is a promising neuroprotective agent that should be further
      evaluated and developed for future prevention and treatment of microglia-mediated
      neuroinflammatory conditions including PD. 

PMID- 25983276
TI  - Hydrogen inhalation protects against acute lung injury induced by hemorrhagic
      shock and resuscitation.
AB  - INTRODUCTION: Hemorrhagic shock followed by fluid resuscitation (HS/R) triggers
      an inflammatory response and causes pulmonary inflammation that can lead to acute
      lung injury (ALI). Hydrogen, a therapeutic gas, has potent cytoprotective,
      antiinflammatory, and antioxidant effects. This study examined the effects of
      inhaled hydrogen on ALI caused by HS/R. METHODS: Rats were subjected to
      hemorrhagic shock by withdrawing blood to lower blood pressure followed by
      resuscitation with shed blood and saline to restore blood pressure. After HS/R,
      the rats were maintained in a control gas of similar composition to room air or
      exposed to 1.3% hydrogen. RESULTS: HS/R induced ALI, as demonstrated by
      significantly impaired gas exchange, congestion, edema, cellular infiltration,
      and hemorrhage in the lungs. Hydrogen inhalation mitigated lung injury after
      HS/R, as indicated by significantly improved gas exchange and reduced cellular
      infiltration and hemorrhage. Hydrogen inhalation did not affect hemodynamic
      status during HS/R. Exposure to 1.3% hydrogen significantly attenuated the
      upregulation of the messenger RNAs for several proinflammatory mediators induced
      by HS/R. Lipid peroxidation was reduced significantly in the presence of
      hydrogen, indicating antioxidant effects. CONCLUSION: Hydrogen, administered
      through inhalation, may exert potent therapeutic effects against ALI induced by
      HS/R and attenuate the activation of inflammatory cascades.

PMID- 25983277
TI  - Genetically determined prospect to become long-lived is associated with less
      abdominal fat and in particular less abdominal visceral fat in men.
AB  - PURPOSE: familial longevity is marked by an exceptionally healthy metabolic
      profile and low prevalence of cardiometabolic disease observed already at middle
      age. We aim to investigate whether regional body fat distribution, which has
      previously shown to be associated with cardiometabolic risk, is different in
      offspring of long-lived siblings compared with controls. METHODS: our
      institutional review board approved the study, and all participants (n = 344,
      average age in years 65.6) gave written informed consent. Offspring (n = 175) of
      non-agenarian siblings were included. Their partners (n = 169) were enrolled as
      controls. For abdominal visceral adipose tissue (VAT) and subcutaneous adipose
      tissue (SAT) measurements, a single-slice 8.0 mm computed tomography (CT)
      acquisition was planned at the level of the 5th lumbar vertebra. In addition,
      participants underwent prospectively electrocardiography-triggered unenhanced
      volumetric CT of the heart. Abdominal VAT and SAT areas (cm(2)) and epicardial
      adipose tissue (EAT) volumes (ml) were acquired by semi-automated segmentation
      techniques. Linear regression analysis was performed adjusting for cardiovascular
      risk factors. RESULTS: total abdominal fat areas were smaller in male offspring
      compared with controls (353.0 versus 382.9 cm(2), P = 0.022). The association
      between low abdominal VAT areas in male offspring (149.7 versus 167.0 cm(2) in
      controls, P = 0.043) attenuated after additional adjustment for diabetes (P =
      0.078). Differences were not observed for females. EAT volumes were similar
      between offspring of long-lived siblings and controls. CONCLUSION: males who have
      genetically determined prospect to become long-lived have less abdominal fat and
      in particular less abdominal VAT compared with controls.

PMID- 25983279
TI  - Body mass index, waist circumference, visceral adiposity, and cardiometabolic
      risk profile.

PMID- 25983278
TI  - Trends of Hospitalizations in the United States from 2000 to 2012 of Patients >60
      Years With Aortic Valve Disease.
AB  - In recent years, there has been an increased emphasis on the diagnosis and
      treatment of valvular heart disease and, in particular, aortic stenosis. This has
      been driven in part by the development of innovative therapeutic options and by
      an aging patient population. We hypothesized an increase in the number of
      hospitalizations and the economic burden associated with aortic valve disease
      (AVD). Using Nationwide Inpatient Sample from 2000 to 2012, AVD-related
      hospitalizations were identified using International Classification of Diseases,
      Ninth Revision, Clinical Modification, code 424.1, as the principal discharge
      diagnosis. Overall AVD hospitalizations increased by 59% from 2000 to 2012. This
      increase was most significant in patients >80 years and those with higher burden
      of co-morbidities. The most frequent coexisting conditions were hypertension,
      heart failure, renal failure, anemia, and diabetes. Overall inhospital mortality
      of patients hospitalized for AVD was 3.8%, which significantly decreased from
      4.5% in 2000 to 3.5% in 2012 (p <0.001). The largest decrease in mortality was
      seen in the subgroup of patients who had heart failure (62% reduction), higher
      burden of co-morbidities (58% reduction), and who were >80 years (53% reduction).
      There was a substantial increase in the cost of hospitalization in the last
      decade from $31,909 to $38,172 (p <0.001). The total annual cost for AVD
      hospitalization in the United States increased from $1.3 billion in 2001 to $2.1
      billion in 2011 and is expected to increase to nearly 3 billion by 2020. The last
      decade has witnessed a significant increase in hospitalizations for AVD in the
      United States. The associated decrease in inhospital mortality and increase in
      the cost of hospitalization have considerably increased the economic burden on
      the public health system.

PMID- 25983280
TI  - Effect of correction of anemia on echocardiographic and clinical parameters in
      patients with aortic stenosis involving a three-cuspid aortic valve and normal
      left ventricular ejection fraction.
AB  - The objective of the study is to investigate the impact of anemia (defined as
      hemoglobin concentration of <12 g/dl in women and 13 g/dl in men) on prognosis
      and to study the effect of recovery from anemia on echocardiographic and clinical
      parameters in patients with aortic stenosis (AS). This was a prospective study in
      315 patients with moderate or severe AS. Patients with anemia received oral iron
      (ferrous sulfate with mucoproteose, 160 mg iron/day) and erythropoietin, if
      needed, or intravenous iron, if necessary. The following tests were performed
      before and after normalization of hemoglobin values: echocardiogram, 6-minute
      walk test, N-terminal B-type natriuretic peptide, and measures of depression,
      cognitive impairment, and dependence. Patient mean age was 74 years (SD 9). Mean
      follow-up was 25 months (SD 8). Anemia prevalence in the overall group was 22% (n
      = 70). Patients who are anemic had a higher rate of complications at follow-up
      (mortality, hospital admission, or need for valve procedure; 80% vs 62%, p =
      0.009). In total, 89% of patients recovered from anemia, with a mean time to
      recovery of 4.6 weeks (SD 1.4). Improvements were observed on echocardiographic
      parameters of peak velocity (4.1 to 3.7 m/s, p = 0.02) and mean gradient (44 to
      35 mm Hg, p = 0.02). Performance on the 6-minute walk test improved from 235 to
      303 m (p <0.001). Median N-terminal B-type natriuretic peptide value decreased
      from 612 to 189 pg/dl (p <0.001). In conclusion, patients with AS and anemia have
      a worse prognosis than those without anemia. Resolution of anemia is associated
      with improvements in echocardiographic parameters and functional status,
      suggesting that treatment of iron deficiency is a relevant option in the
      management of patients with AS, particularly in nonoperable cases.

PMID- 25983281
TI  - Significance of low plasma levels of brain-derived neurotrophic factor in
      patients with heart failure.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family,
      which regulates neuronal differentiation and functions. Low levels of BDNF are
      because of psychological stress and potentially play a role in the pathogenesis
      of depression and cognition disorders. Because psychological stress and
      depression are associated with increased risk of heart failure (HF), the
      pathogenic link between HF and psychological status has attracted clinical
      attention. We hypothesized that plasma BDNF levels might be decreased in patients
      with HF and that BDNF could be a key factor associated with HF. We evaluated
      plasma BDNF levels in 242 patients with HF and 80 subjects without HF who are age
      and gender matched. Plasma BDNF levels were significantly lower in patients with
      HF (3,712 pg/ml [2,124 to 6,180]) than those without HF (7,247 pg/ml [5,388 to
      9,255], p <0.001) and lower in patients with HF with the New York Heart
      Association functional class III than class I (p = 0.01) and class II (p <0.001).
      Log BDNF levels correlated negatively with log B-type natriuretic peptide (r = 
      0.203, p = 0.03) in patients with HF. Of 61 acute decompensated patients with HF,
      plasma BDNF levels were significantly higher at discharge (4,194 pg/ml [2,356 to
      6,916]) compared with those at admission (2,749 pg/ml [1,380 to 4,161], p =
      0.003). Multivariate logistic regression analysis identified log BDNF level as a
      significant correlate with the presence of HF (odds ratio 0.82; 95% confidence
      interval 0.76 to 0.91, p <0.001). In conclusion, plasma BDNF levels were
      decreased in patients with HF and associated with HF severity. BDNF could be a
      potentially clinically useful biomarker of HF reflecting possible cardio-neuronal
      linkage.

PMID- 25983282
TI  - [Acute pancreatitis due to venous artery malformation].

PMID- 25983283
TI  - [Two-year incidence of new immune-mediated inflammatory diseases in patients with
      inflammatory bowel disease: A study in the AQUILES cohort].
AB  - OBJECTIVE: To describe the 2-year incidence of new immune-mediated inflammatory
      diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with
      inflammatory bowel disease (IBD) included in the AQUILES study. MATERIALS AND
      METHODS: Over a 2-year period, 341 patients with IBD (53% women, mean age 40
      years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and
      indeterminate colitis (1.4%) were followed up. New diagnoses made during follow
      up were based on reports of the corresponding specialists (rheumatologists,
      ophthalmologists, and dermatologists). RESULTS: A total of 22 new diagnoses of
      immune-mediated inflammatory diseases were established in 21 patients (cumulative
      incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26
      cases per 10,000 patient-years). Most diagnoses were new cases of
      spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune
      mediated inflammatory diseases was similar in patients with Crohn's disease
      (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2
      13.6). On multivariate analysis, the incidence of new immune-mediated
      inflammatory diseases was significantly associated with a family history of IBD
      (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal
      manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2). CONCLUSIONS: In patients
      with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years
      of follow-up was 6.5%. These diseases were more frequent in patients with
      extraintestinal manifestations of IBD and a family history of IBD.

PMID- 25983284
TI  - A novel bioelectrochemical interface based on in situ synthesis of gold
      nanostructures on electrode surfaces and surface activation by Meerwein's salt. A
      bioelectrochemical sensor for glucose determination.
AB  - A novel effective bioelectrochemical sensor interface for enzyme biosensors is
      proposed. The method is based on in situ synthesis of gold nanostructures (5-15
      nm) on the thin-film electrode surface using the oleylamine (OA) method, which
      provides a high-density, stable, electrode interface nanoarchitecture. New method
      to activate the surface of the OA-stabilized nanostructured electrochemical
      interface for further functionalization with biomolecules (glucose oxidase
      enzyme) using Meerwein's salt is proposed. Using this approach a new biosensor
      for glucose determination with improved analytical characteristics: wide working
      range of 0.06-18.5mM with a sensitivity of 22.6 +/- 0.5 MUAmM(-1)cm(-2), limit of
      detection 0.02 mM, high reproducibility, and long lifetime (60 d, 93%) was
      developed. The surface morphology of the electrodes was characterized by scanning
      electron microscopy (SEM). The electrochemical properties of the interface were
      studied by cyclic voltammetry and electrochemical impedance spectroscopy using a
      Fe(II/III) redox couple. The studies revealed an increase in the electroactive
      surface area and a decrease in the charge transfer resistance following surface
      activation with Meerwein's reagent. A remarkably enhanced stability and
      reproducibility of the sensor was achieved using in situ synthesis of gold
      nanostructures on the electrode surface, while surface activation with Meerwein's
      salt proved indispensable in achieving an efficient bioelectrochemical interface.

PMID- 25983285
TI  - Posttraumatic stress disorder's dysphoria dimension and relations with
      generalized anxiety disorder symptoms.
AB  - The present study investigated symptom relations between two highly comorbid
      disorders--posttraumatic stress disorder (PTSD) and generalized anxiety disorder
      (GAD)--by exploring their underlying dimensions. Based on theory and prior
      empirical research it was expected that the dysphoria factor of PTSD would be
      more highly related to GAD. As part of a longitudinal project of mental health
      among Ohio National Guard Soldiers, 1266 subjects were administered the
      Posttraumatic Stress Disorder Checklist (PCL) and Generalized Anxiety Disorder-7
      scale (GAD-7). Confirmatory factor analyses (CFAs) were conducted to examine two
      models of PTSD and to determine which PTSD factors were more related to the GAD
      factor. The results indicate that the GAD factor was significantly more highly
      correlated with PTSD's dysphoria factor than with all other PTSD factors,
      including PTSD's reexperiencing factor, avoidance factor, and hyperarousal
      factor. Results indicate GAD was not significantly more highly correlated with
      numbing than most other factors of PTSD. The results are consistent with prior
      research. Implications of the results are discussed in regards to PTSD in DSM-5,
      comorbidity and diagnostic specificity.

PMID- 25983286
TI  - Outcomes of burns in the elderly: revised estimates from the Birmingham Burn
      Centre.
AB  - Outcomes after burn have continued to improve over the last 70 years in all age
      groups including the elderly. However, concerns have been raised that survival
      gains have not been to the same magnitude in elderly patients compared to younger
      age groups. The aims of this study were to analyze the recent outcomes of elderly
      burn injured patients admitted to the Birmingham Burn Centre, compare data with a
      historical cohort and published data from other burn centres worldwide. A
      retrospective review was conducted of all patients >=65 years of age, admitted to
      our centre with cutaneous burns, between 2004 and 2012. Data was compared to a
      previously published historical cohort (1999-2003). 228 patients were included.
      The observed mortality for the study group was 14.9%. The median age of the study
      group was 79 years, the male to female ratio was 1:1 and median Total Body
      Surface Area (TBSA) burned was 5%. The incidence of inhalation injury was 13%.
      Median length of stay per TBSA burned for survivors was 2.4 days/% TBSA.
      Mortality has improved in all burn size groups, but differences were highly
      statistically significant in the medium burn size group (10-20% TBSA, p<=0.001).
      Burn outcomes in the elderly have improved over the last decade. This reduction
      has been impacted by a reduction in overall injury severity but is also likely
      due to general improvements in burn care, improved infrastructure, implementation
      of clinical guidelines and increased multi-disciplinary support, including
      Geriatric physicians.

PMID- 25983287
TI  - Incentives for smoking cessation.
AB  - BACKGROUND: Material or financial incentives are widely used in an attempt to
      precipitate or reinforce behaviour change, including smoking cessation. They
      operate in workplaces, in clinics and hospitals, and to a lesser extent within
      community programmes. In this third update of our review we now include trials
      conducted in pregnant women, to reflect the increasing activity and resources now
      targeting this high-risk group of smokers. OBJECTIVES: To determine whether
      incentives and contingency management programmes lead to higher long-term quit
      rates. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group
      Specialised Register, with additional searches of MEDLINE, EMBASE, CINAHL and
      PsycINFO. The most recent searches were in December 2014, although we also
      include two trials published in 2015. SELECTION CRITERIA: We considered
      randomised controlled trials, allocating individuals, workplaces, groups within
      workplaces, or communities to experimental or control conditions. We also
      considered controlled studies with baseline and post-intervention measures. We
      include studies in a mixed-population setting (e.g. community-, work-,
      institution-based), and also, for this update, trials in pregnant smokers. DATA
      COLLECTION AND ANALYSIS: One author (KC) extracted data and a second (JH-B)
      checked them. We contacted study authors for additional data where necessary. The
      main outcome measure in the mixed-population studies was abstinence from smoking
      at longest follow-up, and at least six months from the start of the intervention.
      In the trials of pregnant smokers abstinence was measured at the longest follow
      up, and at least to the end of the pregnancy. MAIN RESULTS: Twenty-one mixed
      population studies met our inclusion criteria, covering more than 8400
      participants. Ten studies were set in clinics or health centres, one in Thai
      villages served by community health workers, two in academic institutions, and
      the rest in worksites. All but six of the trials were run in the USA. The
      incentives included lottery tickets or prize draws, cash payments, vouchers for
      goods and groceries, and in six trials the recovery of money deposited by those
      taking part. The odds ratio (OR) for quitting with incentives at longest follow
      up (six months or more) compared with controls was 1.42 (95% confidence interval
      (CI) 1.19 to 1.69; 17 trials, [20 comparisons], 7715 participants). Only three
      studies demonstrated significantly higher quit rates for the incentives group
      than for the control group at or beyond the six-month assessment: One five-arm
      USA trial compared rewards- and deposit-based interventions at individual and
      group level, with incentives available up to USD 800 per quitter, and
      demonstrated a quit rate in the rewards groups of 8.1% at 12 months, compared
      with 4.7% in the deposits groups. A direct comparison between the rewards-based
      and the deposit-based groups found a benefit for the rewards arms, with an OR at
      12 months of 1.76 (95% CI 1.22 to 2.53; 2070 participants). Although more people
      in this trial accepted the rewards programmes than the deposit programmes, the
      proportion of quitters in each group favoured the deposit-refund programme.
      Another USA study rewarded both participation and quitting up to USD 750, and
      achieved sustained quit rates of 9.4% in the incentives group compared with 3.6%
      for the controls. A deposit-refund trial in Thailand also achieved significantly
      higher quit rates in the intervention group (44.2%) compared with the control
      group (18.8%), but uptake was relatively low, at 10.5%. In the remaining trials,
      there was no clear evidence that participants who committed their own money to
      the programme did better than those who did not, or that contingent rewards
      enhanced success rates over fixed payment schedules. We rated the overall quality
      of the older studies as low, but with later trials (post-2000) more likely to
      meet current standards of methodology and reporting.Eight of nine trials with
      usable data in pregnant smokers (seven conducted in the USA and one in the UK)
      delivered an adjusted OR at longest follow-up (up to 24 weeks post-partum) of
      3.60 (95% CI 2.39 to 5.43; 1295 participants, moderate-quality studies) in favour
      of incentives. Three of the trials demonstrated a clear benefit for contingent
      rewards; one delivered monthly vouchers to confirmed quitters and to their
      designated 'significant other supporter', achieving a quit rate in the
      intervention group of 21.4% at two months post-partum, compared with 5.9% among
      the controls. Another trial offered a scaled programme of rewards for the
      percentage of smoking reduction achieved over the course of the 12-week
      intervention, and achieved an intervention quit rate of 31% at six weeks post
      partum, compared with no quitters in the control group. The largest (UK-based)
      trial provided intervention quitters with up to GBP 400-worth of vouchers, and
      achieved a quit rate of 15.4% at longest follow-up, compared to the control quit
      rate of 4%. Four trials confirmed that payments made to reward a successful quit
      attempt (i.e. contingent), compared to fixed payments for attending the antenatal
      appointment (non-contingent), resulted in higher quit rates. Front-loading of
      rewards to counteract early withdrawal symptoms made little difference to quit
      rates. AUTHORS' CONCLUSIONS: Incentives appear to boost cessation rates while
      they are in place. The two trials recruiting from work sites that achieved
      sustained success rates beyond the reward schedule concentrated their resources
      into substantial cash payments for abstinence. Such an approach may only be
      feasible where independently-funded smoking cessation programmes are already
      available, and within a relatively affluent and educated population. Deposit
      refund trials can suffer from relatively low rates of uptake, but those who do
      sign up and contribute their own money may achieve higher quit rates than reward
      only participants. Incentive schemes conducted among pregnant smokers improved
      the cessation rates, both at the end-of-pregnancy and post-partum assessments.
      Current and future research might continue to explore the scale, loading and
      longevity of possible cash or voucher reward schedules, within a variety of
      smoking populations.

PMID- 25983288
TI  - Different pathways of macrophage activation and polarization.
AB  - Monocytes are short-lived cells and undergo spontaneous apoptosis every day.
      Inflammatory responses may induce dramatic up-regulation of monocyte survival and
      differentiation. When monocytes are recruited to an area of infection they may
      differentiate into macrophages. In different microenvironments macrophages
      polarize into two types. The M1 or classically activated macrophages are
      characterized by the high ability to produce pro-inflammatory cytokines and the
      production of NO through the induced synthesis of iNOS. The M2 or alternatively
      activated macrophages are divided into 3 subtypes, M2 a, b and c, and they have
      anti-inflammatory properties. Mediators of M1 macrophage TLR-dependent
      polarization include transcription factors such as NF-kappaB, AP-1, PU.1,
      CCAAT/enhancer-binding protein alpha (C/EBP-alpha), STAT1 as well as interferon
      regulatory factor 5 (IRF5), while the transcription factors which promote M2
      activation include IRF4, C/EBP-beta, Kruppel-like factor 4 (KLF4), STAT6 and
      PPARgamma receptor. 

PMID- 25983289
TI  - Assessment of cytotoxic potential of root canal sealers after hardening - an ex
      vivo study.
AB  - AIM: The aim of this study was to perform a comparative assessment of the toxic
      action of root canal sealers currently on the market on human gingival
      fibroblasts after setting. MATERIAL/METHODS: The inserts with an equal quantity
      of set root canal sealers were transferred into 24-well culture dishes containing
      human gingival fibroblasts cultured in Dulbecco's Modified Eagle's Medium (DMEM)
      supplemented with 10% fetal calf serum (FCS). The dishes with materials were
      incubated at 37 degrees C, 100% humidity and in an atmosphere of 5% CO2 for 24 h.
      The cytotoxic effects of the root canal materials were measured by the
      mitochondrial succinate dehydrogenase activity in living cells using tetrazolium
      bromide (MTT assay). RESULTS: Epiphany and Sealapex exhibited high toxicity
      towards human gingival fibroblasts - 25.57% +/- 0.88 and 27.63 % +/- 2.35
      respectively (less than 30% live cells in the culture). The remaining materials
      were characterized by lack of a cytotoxic effect (over 90% of live cells in the
      culture). None of the preparations exhibited moderate or low toxicity.
      CONCLUSIONS: The majority of root canal sealers tested after hardening were well
      tolerated by human gingival fibroblasts. Only two materials were characterized by
      high toxicity: with methacrylate (Epiphany) and calcium hydroxide (Sealapex).

PMID- 25983290
TI  - Deep vein thrombosis of the lower limbs in intravenous drug users.
AB  - BACKGROUND: Addiction to intravenously administered drugs has been a serious
      epidemiological problem for years. Among the related health complications, deep
      vein thrombosis (DVT) is one of the most important. This paper provides an
      illustrative presentation of DVT in intravenous drug users (IDUs), HIV-positive
      subjects among them. METHODS: We searched PubMed, Ovid Journals, Scopus,
      ScienceDirect, Cochrane Library, Google Scholar and references from articles
      obtained. The main terms used to identify appropriate studies of DVT in IDUs were
      'intravenous drug users', 'substance-related disorders' and 'deep vein
      thrombosis'. RESULTS: No guidelines exist for DVT in intravenous drug users. As
      many as 47.6% of IDUs report having suffered from DVT. IDUs may constitute
      approx. 50% of patients under 40 years of age with DVT, this being promoted by
      multiple vein punctures, groin injections, lack of sterility, insoluble
      microparticles and other factors. The clinical appearance is more complex than in
      the general population, which also makes prognosis more difficult. HIV infection
      can worsen DVT. It often appears as proximal iliofemoral thrombosis, accompanied
      by local and general complications. Ultrasound with a compression test is an
      objective method of choice, but must often be complemented with computed
      tomography. Antithrombotic therapy in IDUs needs to be applied individually. The
      optimal method is supervised therapy at addiction treatment services.
      CONCLUSIONS: Individual and public preventive measures, among them locally
      prepared guidelines for DVT in IDUs, may be the most important processes capable
      of effectively reducing the morbidity of septic and non-septic DVT.

PMID- 25983291
TI  - [The role of the bone marrow microenvironment in the pathogenesis of multiple
      myeloma].
AB  - Multiple myeloma (MM) is one of the most common hematologic malignancies. It
      remains an incurable disease, so far. The mainstay of treatment for decades was
      pointless therapy with cytostatic agents and immunosuppressant's. Because myeloma
      is most common in the elderly population, vulnerable to aggressive therapy, non
      specific treatment approaches led to poor patient survival. Intensive study of
      MM, allowed identification of the molecular interactions between myeloma cells
      and bone marrow tumour microenvironment, responsible for the development of the
      disease and associated complications, such as osteolytic bone lesions.
      Understanding the molecular mechanisms of action of adhesion molecules, cytokines
      and signalling pathways involved in the development of myeloma, has led to
      develop of novel, targeted therapies to improve the quality of patients life and
      significantly prolong the median survival time. This paper discusses the current
      state of knowledge of signalling pathways involved in the progression of cancer
      and the destruction of bone tissue, with particular emphasis on interactions with
      the bone marrow microenvironment of the tumour. 

PMID- 25983292
TI  - [The role of the PD-1 protein in pathogenesis of autoimmune diseases, with
      particular consideration of rheumatoid arthritis and systemic lupus
      erythematosus].
AB  - Polymorphism of the PDCD1 gene for the PD-1 protein (programmed cell death 1,
      encoded by PDCD1) is significantly associated with higher incidence of autoimmune
      diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus
      (SLE), which may suggest the participation of PD-1 in the pathogenesis of these
      diseases. Over 30 single nucleotide polymorphisms (SNPs) have been identified in
      the human PDCD1 gene. SNPs in the PDCD1 gene in humans have demonstrated relevant
      associations with a higher risk of developing autoimmune diseases in certain
      ethnic groups. RA and SLE are chronic connective tissue diseases with autoimmune
      background. RA is a common form of chronic, progressive arthritis in adults. SLE
      is characterized by chronic inflammation in most of the body's tissues and
      organs, leading to a complex clinical syndrome. The pathogenesis of the
      autoimmune diseases is not well examined. However, genetic factors, immunological
      disorders and environmental factors are believed to play a decisive role in the
      occurrence of the illnesses. Complex immune system disorders are responsible for
      the development of SLE. In RA activated T cells produce cytokines such as
      interleukin 2 (IL-2) and interferon gamma (IFN-gamma) that stimulate macrophages
      and monocytes. The main role of PD-1 is inhibition of T-cell proliferation,
      inhibition of production of IL-2, interleukin 10 (IL-10) and IFN-gamma, and
      inhibition of activation of autoreactive lymphocytes. Because of the wide range
      of ligand distribution in the body, the biological significance of protein refers
      to almost all aspects of the immune response, including autoimmunology, tumour
      immunology, inflammation, transplantation, and allergy. Currently, there is
      increasing interest in the importance of PD-1 in the maintenance of immunological
      balance and its role in the development of autoimmune diseases. We summarize the
      PD-1 research in patients with RA and SLE in recent years. 

PMID- 25983293
TI  - Analysis of peripheral blood immune cells after prophylactic immunization with
      HPV-16/18 ASO4-adjuvanted vaccine.
AB  - Persistent infection with oncogenic types of human papillomavirus (HPV) is a
      causal factor for more than 99% of cervical cancers. Recently, prophylactic
      vaccines have been developed to prevent infections with cancer-associated HPV
      types (HPV16 and HPV18). The aim of this study was to analyze the changes in the
      immune system that occur within four weeks of the first dose of HPV-16/18 ASO4
      adjuvanted vaccine. Assessment of the percentages of selected cell populations in
      peripheral blood of 20 healthy volunteers vaccinated with Cervarix was performed
      using flow cytometry. The analysis revealed an increase in the proportion of
      activated B and CD4+ T helper cells and an absence of significant differences in
      cytotoxic CD8+ T lymphocytes, indicating activation of the humoral response after
      vaccination, without a significant effect on cellular response. There were no
      significant changes in the NK cell population, and there was a reduction of the
      percentage of NKT-like cells, which may result from expiry of the primary
      response at the time of analysis. The presented results are preliminary, and in
      the context of the increasing use of the anti-HPV vaccine, it would be worth
      continuing the study in larger groups of patients and at earlier and later time
      points in combination with the measurement of specific anti-HPV16 and -HPV18
      antibody levels. Such an assessment could therefore contribute not only to better
      understanding of the exact mechanism of action of the vaccine, but also to
      defining the immunological parameters that determine its effectiveness. 

PMID- 25983294
TI  - [Therapeutic potential of secondary metabolites produced in the hairy roots
      cultures].
AB  - Plants have always been a source of many valuable substances for humans. Growing
      advancement of methods of modern biotechnology, combined with genetic engineering
      techniques, gradually increase the variety of compounds obtained, the number of
      plant species used and the production efficiency. Consequently, there is an
      undebatable interest in biotechnological production of such compounds, especially
      those pharmacologically active, that can be used in treatment of neoplastic,
      viral, and many other types of diseases. Most of these compounds represent a
      diverse group of secondary metabolites. One of the effective ways of obtaining
      such molecules is the utilization of hairy roots cultures. The advantages of such
      systems make them an attractive method of obtaining important plant-derived
      compounds, creating an interesting alternative to other methods, including the
      cell suspension cultures or expensive chemical syntheses.

PMID- 25983295
TI  - [Identification of proteomic biomarkers of preeclampsia using protein microarray
      and tandem mass spectrometry].
AB  - Preeclampsia (PE) is the leading cause of death of the fetus and the mother. The
      exact pathomechanism has not so far been clarified. PE coexists with many other
      diseases, but it is often difficult to explain the association between them and
      find a clear reason for their occurrence. There are many predictive factors, but
      none are highly specific in preeclampsia. The diagnosis of preeclampsia seems to
      be very complex, which is another argument for the exploration of knowledge on
      this subject. Although many of the discoveries have hitherto been made in the
      field of proteomics, still no single specific biomarker of preeclampsia has been
      discovered. Research at the genome level is important because it can help us
      understand the genetic predisposition of patients affected by this disease.
      Nevertheless, researchers have recently become more interested in the
      pathophysiology of PE, and they are trying to answer the question: what is the
      real, direct cause of preeclampsia? Thus, the discovery of a protein that is a
      good predictor of preeclampsia development would significantly accelerate the
      medical care of pregnant women, and consequently reduce the risk of occurrence of
      HELLP syndrome and fetal death. Apart from the predictive and diagnostic
      function, such a discovery would help us to better understand the pathogenesis of
      preeclampsia and to find in the future a medical drug to suppress this disease.
      In order to make a breakthrough in this field, scientists need to use the most
      modern methods of proteomics, which allow for the analysis of small amounts of
      biological material in the shortest possible time, thereby giving a lot of
      information about existing proteins in the sample. Such optimization allows two
      methods, most commonly used by researchers: tandem mass spectrometry and protein
      microarray technique. 

PMID- 25983296
TI  - [Inhibitors of microtubule polymerization- new natural compounds as potential
      anti-cancer drugs].
AB  - Inhibitors of microtubule polymerization are compounds which, by binding to the
      tubulin dimer, prevent the normal course of cell division and lead to cell death.
      They cause inhibition of mitosis, affect the cytoskeleton and disrupt the process
      of angiogenesis. Inhibitors of microtubule polymerization include natural
      substances, synthetic and semi-synthetic analogs. They contain a group of
      compounds having the ability to bind to the vinca alkaloid and colchicine domain
      of beta-tubulin. Among them are vinca alkaloids, dolastatins and halichondrins,
      which connect to the vinca alkaloids domain, and combretastatins binding the
      colchicine site of protein. Tumor cells have greater capacity for cell
      proliferation and are also more susceptible to damage by microtubule inhibitors.
      Their action has been widely used in cancer therapy. 

PMID- 25983297
TI  - Prognostic value of HER3, PTEN and p-HER2 expression in patients with
      HER2positive breast cancer.
AB  - BACKGROUND: HER2 overexpression is an unfavorable prognostic factor in patients
      with breast cancer, but it is also a target for the monoclonal antibody
      trastuzumab, which is effective in adjuvant and palliative settings. HER2
      positivity is an inclusion criterion for immunotherapy, but it is not a positive
      predictive factor, and only half of patients benefit from the treatment. AIM: The
      aim of this study was to evaluate the prognostic and predictive value of HER3,
      PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of
      patients treated with trastuzumab in an adjuvant or palliative regimen.
      MATERIAL/METHODS: Immunohistochemical (IHC) analysis with 3 antibodies specific
      to the proteins was performed in tumor specimens obtained from 81 HER2-positive
      patients treated with trastuzumab. RESULTS: HER3 overexpression was present in
      55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0%
      and 34.6% of them, respectively. HER3 overexpression and PTEN positivity
      correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2
      positivity correlated with more advanced clinical stage of the disease (p=0.032).
      There was no correlation between the proteins' expression and survival for 31
      patients treated with trastuzumab in the palliative regimen. DISCUSSION: HER3
      overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2
      positive patients correlate with more advanced clinical stage of breast cancer.
      Expression of these proteins does not predict outcome of trastuzumab treatment.

PMID- 25983298
TI  - [Selected aspects of Clostridium difficile infection].
AB  - Clostridium difficile pathogen is a cause of the most frequent nosocomial
      infection, which is antibiotic-associated diarrhea. Antibiotic treatment causes
      disruption of the microbiome balance, which makes the gut a friendly environment
      for the pathogen. It leads to pseudomembranous colitis, toxic megacolon and even
      death. Clostridium difficile infection (CDI) is particularly dangerous to elderly
      patients, leading to the highest mortality rate. C. difficile is equipped with
      many virulence factors such as toxin A and B, binary toxin CDT, flagellum, S
      layer proteins, Cwp66 and GroEL proteins, protease Cwp84, fibronectin-binding
      protein and the ability to form biofilm and spores. Problems with anti-CDI
      therapy prompt researchers and clinicians to seek alternative ways of therapy.
      Identification of immunological epitopes in outer layer proteins and the use of
      them as antigens for anti-CDI vaccines would be a rational approach to prevent
      the disease, but unfortunately such vaccines are not available yet. In this
      article we review the course of the disease, virulence and risk factors. We
      summarize briefly epidemiological data and the latest achievements in CDI
      treatment. 

PMID- 25983299
TI  - [Selected aspects of Chlamydophila pneumoniae infections].
AB  - Chlamydophila pneumoniae was taxonomically separated from strain TWAR - an
      abbreviation of the strain isolated from humans TW-183 (material from the eye of
      a child in Taiwan in 1965) and AR-39 (material from a student's throat swab with
      acute changes within airways in Seattle in 1983). The basis of separation of the
      C. pneumoniae species was the unique structure of the elementary bodies.
      Infection caused by C. pneumoniae is often asymptomatic (60-80% of all
      infections). Symptomatic infections of the upper respiratory tract relate to
      pharyngitis, laryngitis, sinusitis and the lower respiratory tract: bronchitis
      and pneumonia. C. pneumoniae infection often transforms into a chronic,
      clinically oligo- or asymptomatic form. The chronic inflammatory process is
      associated by many authors with the pathogenesis of coronary artery disease,
      endocarditis, atherosclerosis, hypertension, vasculitis, multiple sclerosis,
      sarcoidosis, and asthma. C. pneumoniae has a specific tropism and exhibits
      cytotoxic activity towards the airway epithelium, in which it proliferates and
      destroys infected cells by lysis. Entry of these bacteria to the human body leads
      to activation of first non-specific and then specific resistance mechanisms and
      the development of a local inflammatory process. Diagnosis of C. pneumoniae
      should be confirmed only after the exclusion of typical micro-organisms causing
      respiratory infections. It is important to pay attention to the fact that the
      epidemiological data on the incidence of C. pneumoniae infections in different
      age groups of patients are variable depending on the type of diagnostic methods
      used in the research. Chlamydia are resistant to most antibiotics that are
      routinely used in respiratory tract infections. These bacteria are susceptible to
      antibiotics that disrupt the synthesis of DNA and proteins, such as macrolides,
      tetracyclines, and fluoroquinolones. 

PMID- 25983300
TI  - [The role of blood platelets in infections].
AB  - Platelets are primarily associated with their main function, hemostasis, although
      it is known that these cells also exhibit biological activity in cancer
      progression, inflammation and infectious processes. During infection platelets,
      due to the expression of specific receptors - Toll-like receptors (TLRs) - which
      recognize molecular patterns associated with pathogens - pathogen-associated
      molecular patterns (PAMPs) - are activated by the presence of microorganism
      components and/or substances released from damaged cells/tissue. Further
      antimicrobial activity of platelets is based on their capacity for phagocytosis,
      generation of reactive oxygen species (ROS), and the synthesis, storage and
      release of proteins/peptides with antimicrobial activity. Another mechanism of
      platelet action is their immunomodulatory activity. It is based mainly on the
      ability to secrete chemotactic factors allowing the accumulation of professional
      immunocompetent cells at the site of infection, thus enhancing the effective
      eradication of an infectious agent. In chronic infections, platelets, due to
      release of numerous growth factors and various cytokines, support mechanisms of
      acquired immunity. They accelerate the maturation of dendritic cells, stimulate B
      cells to be immunoglobulin-producing plasma cells and potentiate the activity of
      T cells. Unfortunately, in certain situations (the existence of specific risk
      factors) the interaction of microorganisms with activated platelets may also be
      the cause of pathology within the cardiovascular system. 

PMID- 25983301
TI  - Different body fluid volumes measured by single- and multi-frequency
      bioelectrical impedance analyzers in overweight/obese renal patients.
AB  - INTRODUCTION: Bioelectrical impedance analysis (BIA) is an affordable, non
      invasive and fast alternative method to assess body composition. The purpose of
      this study was to compare two different tetrapolar BIA devices for estimating
      body fluid volumes and body cell mass (BCM) in a clinical setting among patients
      with kidney failure. METHODS: All double measurements were performed by multi
      frequency (MF) and single-frequency (SF) BIA analyzers: a Body Composition
      Monitor (Fresenius Medical Care, Germany) and BIA-101 (Akern, Italy),
      respectively. All procedures were conducted according to the manufacturers'
      instructions (dedicated electrodes, measurement sites, positions, etc). Total
      body water (TBW), extracellular water (ECW), intracellular water (ICW) and BCM
      were compared. The study included 39 chronic kidney disease patients (stage III
      V) with a mean age of 45.8 +/- 8 years (21 men and 18 women) who had a wide range
      of BMI [17-34 kg/m2 (mean 26.6 +/-5)]. RESULTS: A comparison of results from
      patients with BMI <25 vs >=25 revealed a significant discrepancy in measurements
      between the two BIA devices. Namely, in the group with BMI <25 (n=16) acceptable
      correlations were obtained in TBW (r 0.99; p<0.01), ICW (0.92; p<0.01), BCM
      (0.68; p<0.01), and ECW (0.96 p<0.05), but those with BMI >=25 (n=23) showed a
      discrepancy (lower correlations) in TBW (r 0.82; p<0.05), ICW (0.78; p<0.05), BCM
      (0.52; p<0.05), and ECW (0.76; p<0.01). CONCLUSIONS: Since estimates of TBW, ICW
      and BCM by the present BIA devices do not differ in patients with BMI <25, they
      might be interchangeable. This does not hold true for overweight/obese renal
      patients.

PMID- 25983302
TI  - [Glycated albumin as a marker of glycemia in diabetes and its vascular
      complications].
AB  - Effective glycemic control is very important to prevent the onset and the
      progression of chronic complications in diabetic patients. It is known that
      glycation of various proteins is increased in diabetic patients compared with non
      diabetics. Among these glycated proteins, glycated hemoglobin (HbA1c) is commonly
      used as a gold standard index of glycemic control in the clinical setting.
      However, it can be unreliable in conditions affecting the lifespan of
      erythrocytes (120 days) as well as in the clinical state in which glycemic
      control alleviates or deteriorates in a short period. By overcoming the
      shortcomings of HbA1c, glycated albumin (GA) has gained interest as a useful
      index for an intermediate glycation period (2 weeks) and pathogenic protein.
      After giving a brief overview of the key role of HbA1c as a long-term glycemic
      marker, this review focuses on (a) glycation of human albumin and its main
      properties, (b) methods of GA determination, (c) the recent clinical status of GA
      as a glycemic index in diabetic patients and its association with vascular
      complications. Finally, conditions with a possible inaccurate GA level are also
      mentioned. 

PMID- 25983303
TI  - [Telomere length and transrenal DNA isolated from transplanted kidney recipients'
      urine].
AB  - Transplantation is the preferred method of end stage renal insufficiency
      treatment due to better quality of life and extended life of transplanted
      patients. Currently a non-invasive test, which evaluates the risk of acute or
      chronic rejection or deterioration of the transplanted organ's function, is being
      sought. An increase of the transrenal DNA concentration in the urine of urinary
      tract infection patients and in renal graft recipients during an episode of acute
      rejection was observed. There were also reports on shortening of telomeres in
      transplanted organ chromosomes, as the result of accelerated aging of cells, and
      its connection with the onset of chronic allograft nephropathy and the degree of
      its completion, and thus the deterioration of kidney function. The aim of this
      paper is to describe the urine genetic analysis through determining the length of
      the telomeres and the content of transrenal DNA to monitor kidney function and to
      evaluate the prevalence of acute and chronic rejection in patients after kidney
      transplantation. The genetic analysis of the biological material collected from
      patients relies on the determination of transrenal DNA content and length of DNA
      telomeres isolated from the urine of kidney recipients. The presented methods
      assume that the genetic profile of the transplanted organ recipient as well as
      kidney donor can be determined, so the source of the genetic material in the
      urine of the patient can be identified. A measurable effect of these methods' use
      would be to complement the evaluation of the prevalence of acute and chronic
      rejection and transplanted kidney function with a modern, non-invasive method,
      which is the analysis of telomere length from sediment of urine and the content
      of transrenal DNA in the urine. 

PMID- 25983305
TI  - Guidelines concordance of maintenance treatment in euthymic patients with bipolar
      disorder: Data from the national bipolar mania pathway survey (BIPAS) in mainland
      China.
AB  - BACKGROUND: Although the treatment guidelines of bipolar disorders (BPD) have
      spread more than a decade, the concordance with evidence-based guidelines was
      typically low in routine clinical practice. This study is to present the data on
      the maintenance treatment of BPD in mainland China. METHODS: One thousand and
      twenty-three patients who had experienced a euthymia were eligible for entry into
      this survey on the maintenance treatment of BPD. Guidelines disconcordance was
      determined by comparing the medication(s) that patients were prescribed with the
      recommendations in the guidelines of the Canadian Network for Mood and Anxiety
      Treatments. RESULTS: Three hundred and sixty-four patients (35.6%) had not been
      prescribed with the maintenance treatment as guidelines recommendations, and 208
      patients (20.3%) were prescribed with the antidepressants. A longer duration of
      BPD, a depressive episode at first onset, and a recent depressive or mixed
      episode significantly increased the risk for guidelines disconcordance and
      prescribing antidepressant. In contrast, a hospitalization history due to manic
      episode was associated with a significant decrease in the risk for guidelines
      disconcordance and prescribing antidepressant. LIMITATION: This study was a cross
      sectional and retrospective investigation based on medical records. CONCLUSIONS:
      Considering the potentially hazardous effects of inappropriate treatment,
      individualized psychoeducational strategies for subjects with BPD are necessary
      to enhance treatment adherence and close the gap between guidelines and clinical
      practice in mainland China.

PMID- 25983306
TI  - Folding of beta-barrel membrane proteins in lipid bilayers - Unassisted and
      assisted folding and insertion.
AB  - In cells, beta-barrel membrane proteins are transported in unfolded form to an
      outer membrane into which they fold and insert. Model systems have been
      established to investigate the mechanisms of insertion and folding of these
      versatile proteins into detergent micelles, lipid bilayers and even synthetic
      amphipathic polymers. In these experiments, insertion into lipid membranes is
      initiated from unfolded forms that do not display residual beta-sheet secondary
      structure. These studies therefore have allowed the investigation of membrane
      protein folding and insertion in great detail. Folding of beta-barrel membrane
      proteins into lipid bilayers has been monitored from unfolded forms by dilution
      of chaotropic denaturants that keep the protein unfolded as well as from unfolded
      forms present in complexes with molecular chaperones from cells. This review is
      aimed to provide an overview of the principles and mechanisms observed for the
      folding of beta-barrel transmembrane proteins into lipid bilayers, the importance
      of lipid-protein interactions and the function of molecular chaperones and
      folding assistants. This article is part of a Special Issue entitled: Lipid
      protein interactions. 

PMID- 25983304
TI  - Verbal learning impairment in euthymic bipolar disorder: BDI v BDII.
AB  - OBJECTIVES: Cognitive impairment is known to occur in bipolar disorder (BD), even
      in euthymic patients, with largest effect sizes often seen in Verbal Learning and
      Memory Tasks (VLT). However, comparisons between BD Type-I and Type-II have
      produced inconsistent results partly due to low sample sizes. METHODS: This study
      compared the performance of 183 BDI with 96 BDII out-patients on an adapted
      version of the Rey Verbal Learning Task. Gender, age, years of education, mood
      scores and age at onset were all used as covariates. Current medication and a
      variety of illness variables were also investigated for potential effects on VLT
      performance. RESULTS: BDI patients were significantly impaired relative to BDII
      patients on all five VLT outcome measures after controlling for the other
      variables [Effect Sizes=.13-.17]. The impairments seem to be unrelated to drug
      treatment and largely unrelated to illness variables, although age of onset
      affected performance on three outcome measures and number of episodes of mood
      elevation affected performance on one. LIMITATIONS: This study used historical
      healthy controls. Analysis of potential drug effects was limited by insufficient
      participants not being drug free. Cross-sectional nature of the study limited the
      analysis of the potential effect of illness variables. CONCLUSIONS: This study
      replicates earlier findings of increased verbal learning impairment in BDI
      patients relative to BDII in a substantially larger sample. Such performance
      cannot be wholly explained by medication effects or illness variables. Thus, the
      cognitive impairment is likely to reflect a phenotypic difference between bipolar
      sub-types.

PMID- 25983307
TI  - Does hydrogen bonding contribute to lipoperoxidation-dependent membrane fluidity
      variation? An EPR-spin labeling study.
AB  - This study is aimed at making clear the relationship between oxidative stress of
      the phospholipid bilayer and membrane fluidity. Di-(hydroperoxylinoleoyl)
      phosphatidylcholine (diHpLPC) was used as a highly hydroperoxidized and
      unsaturated phospholipid species in order to investigate the issue. Hydrophylic
      Interaction Liquid Chromatography-ElectroSpray Ionization-Mass Spectrometry
      (HILIC-ESI-MS) and NMR spectroscopy were employed to define the structure of the
      peroxidized phospholipid as 1-(9-hydroperoxy-10c,12t)octadecadienoyl-2-(9t,11c-13
      hydroperoxy)octadecadienoyl-sn-glycero-3-phosphorylcholine. This phospholipid's
      ability to form vesicular structures was confirmed by Sepharose 4B gel filtration
      and Dynamic Light Scattering (DLS) of its aqueous suspensions. Fatty acid
      misalignment and fluidity gradient were studied in the bilayer of both supported
      planar bilayers (SPB) and multilamellar vesicles (MLV) made of different
      DLPC/diHpLPC mixtures by means of spin labelling-EPR spectroscopy of either n
      DSPC or 3-doxylcholestane spin labels embedded in the membranes. It was found
      that diHpLPC increases both fatty acid misalignment and rigidification with
      increasing molar ratio in spite of increasing unsaturation of the fatty acid
      core. Basing on our observations, the observed ability of pure diHpLPC to form
      rigid and disordered SPB and MLV bilayers is proposed to be dependent on the
      cross bridging of oxidized linoleoyl chains by mutual hydrogen bonding of
      hydroperoxyl groups. However, the contribution to the observed overall
      rigidification of the model membranes by trans double bonds in the peroxidized
      chains should not be neglected, as a second membrane fluidity effector also
      arising from lipid peroxidation. 

PMID- 25983308
TI  - Dietary sodium and cardiovascular disease.
AB  - Although an essential nutrient, higher sodium intake is associated with
      increasing blood pressure (BP), forming the basis for current population-wide
      sodium restriction guidelines. While short-term clinical trials have achieved low
      intake (<2.0 g/day), this has not been reproduced in long-term trials (>6
      months). Guidelines assume that low sodium intake will reduce BP and reduce
      cardiovascular disease (CVD), compared to moderate intake. However, current
      observational evidence suggests a J-shaped association between sodium intake and
      CVD; the lowest risks observed with 3-5 g/day but higher risk with <3 g/day.
      Importantly, these observational data also confirm the association between higher
      intake (>5 g/day) and increased risk of CVD. Although lower intake may reduce BP,
      this may be offset by marked increases in neurohormones and other adverse effects
      which may paradoxically be adverse. Large randomised clinical trials with
      sufficient follow-up are required to provide robust data on the long-term effects
      of sodium reduction on CVD incidence. Until such trials are completed, current
      evidence suggests that moderate sodium intake for the general population (3-5
      g/day) is likely the optimum range for CVD prevention.

PMID- 25983309
TI  - Speech understanding in noise with the Roger Pen, Naida CI Q70 processor, and
      integrated Roger 17 receiver in a multi-talker network.
AB  - Roger is a digital adaptive multi-channel remote microphone technology that
      wirelessly transmits a speaker's voice directly to a hearing instrument or
      cochlear implant sound processor. Frequency hopping between channels, in
      combination with repeated broadcast, avoids interference issues that have limited
      earlier generation FM systems. This study evaluated the benefit of the Roger Pen
      transmitter microphone in a multiple talker network (MTN) for cochlear implant
      users in a simulated noisy conversation setting. Twelve post-lingually deafened
      adult Advanced Bionics CII/HiRes 90K recipients were recruited. Subjects used a
      Naida CI Q70 processor with integrated Roger 17 receiver. The test environment
      simulated four people having a meal in a noisy restaurant, one the CI user
      (listener), and three companions (talkers) talking non-simultaneously in a
      diffuse field of multi-talker babble. Speech reception thresholds (SRTs) were
      determined without the Roger Pen, with one Roger Pen, and with three Roger Pens
      in an MTN. Using three Roger Pens in an MTN improved the SRT by 14.8 dB over
      using no Roger Pen, and by 13.1 dB over using a single Roger Pen (p < 0.0001).
      The Roger Pen in an MTN provided statistically and clinically significant
      improvement in speech perception in noise for Advanced Bionics cochlear implant
      recipients. The integrated Roger 17 receiver made it easy for users of the Naida
      CI Q70 processor to take advantage of the Roger system. The listening advantage
      and ease of use should encourage more clinicians to recommend and fit Roger in
      adult cochlear implant patients.

PMID- 25983310
TI  - A randomized study of remote monitoring and fluid monitoring for the management
      of patients with implanted cardiac arrhythmia devices.
AB  - AIMS: Only limited comparative data exist on the benefits of fluid monitoring
      (FM) combined with remote monitoring (RM) regarding morbidity and mortality of
      heart failure (HF) patients. This prospective single-centre randomized pilot
      study aimed to estimate the influence of RM in combination with FM on HF
      hospitalizations as well as ventricular tachyarrhythmias and mortality. METHODS
      AND RESULTS: Patients with standard indication for implantable cardioverter
      defibrillator (ICD) or cardiac resynchronization therapy and defibrillator were
      implanted with devices capable of RM and FM, and were followed for 15 months.
      Subjects were randomly allocated to RM including OptiVol and predefined
      management of alerts (remote group), or standard in-office visits every 3 months
      (control group). A total of 176 patients (77% male; 66 +/- 12 years; left
      ventricular ejection fraction (LVEF) 32 +/- 11%; ischemic cardiomyopathy 50%; CRT
      device 50%; primary prevention 85%) were analysed. Cox proportional hazard
      analysis on the time to first HF-related hospitalization showed a hazard ratio of
      1.23 [0.62-2.44] (P = 0.551) favouring the control group. In the remote group, 13
      patients (15%) experienced ICD shocks vs. 10 patients (11%) in the control group
      (P = 0.512). The average time to first ICD shock was 212 +/- 173 days in the
      remote arm and 212 +/- 143 days in the control arm (P = 0.994). The Kaplan-Meier
      estimate of mortality after 1 year was 8.6% (eight deaths) in the remote group
      vs. 4.6% in the control group (six deaths; P = 0.502). CONCLUSION: In a single
      centre randomized pilot study of RM in combination with FM, no significant
      influence on HF-related hospitalizations, ICD shocks, or mortality was found.

PMID- 25983311
TI  - An explicit formula for the coherent SH waves' attenuation coefficient in random
      porous materials with low porosities.
AB  - In this paper, the attenuation coefficient of coherent SH waves in random porous
      material with uniformly randomly distributed elliptical cavities of different
      aspect ratios is studied. Based on an analysis of the mechanism for attenuation,
      a simple macro model for the attenuation coefficient is proposed. The macro model
      says that the attenuation coefficient can be expressed as a function of the mean
      scattering cross section and the number density of cavities at low porosities.
      Then, large-scale numerical simulations using the pre-corrected Fast Fourier
      Transform (pFFT) algorithm accelerated Boundary Element Method (BEM) are
      conducted to specify this macro model. Finally, this macro model is compared with
      four theoretical models derived for composite/porous materials with circular
      inclusions at the porosity p=3.17% and 5%. Results show this macro model agree
      well with three of them. Compared to the existing theoretical models, the form of
      this macro model is simple and has a clear physical meaning. In addition, it is
      applicable to cases with relatively complex cavities. 

PMID- 25983312
TI  - Biothiol-triggered, self-disassembled silica nanobeads for intracellular drug
      delivery.
AB  - Silica-based nanomaterials have demonstrated great potential in biomedical
      applications due to their chemical inertness. However, the degradability and
      endosomal trapping issues remain as rate-limiting barriers during their
      innovation. In this study, we provide a simple yet novel sol-gel approach to
      construct the redox-responsive silica nanobeads (ReSiNs), which could be rapidly
      disassembled upon redox gradient for intracellular drug delivery. The disulfide
      linked scaffold of the nanobead was synthesized by employing the dithiobis
      (succinimidyl propionate) to bridge (3-aminopropyl)-trimethoxysilane. Such silica
      matrix could be efficiently disrupted in response to intracellular glutathione,
      resulting in drug release and collapse of entire nanocarrier. Moreover, the
      ReSiNs exhibited insignificant cytotoxicity before and after the degradation.
      These results indicated the potential of using ReSiNs as a novel silica-based,
      biothiol-degradable nanoplatform for future drug delivery. 

PMID- 25983313
TI  - Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery
      to the brain: Preparation and in vitro investigation.
AB  - Poly(lactic acid), which has an inherent tendency to form colloidal systems of
      low polydispersity, and alkylglyceryl-modified dextran - a material designed to
      combine the non-immunogenic and stabilising properties of dextran with the
      demonstrated permeation enhancing ability of alkylglycerols - have been combined
      for the development of nanoparticulate, blood-brain barrier-permeating, non-viral
      vectors. To this end, dextran, that had been functionalised via treatment with
      epoxide precursors of alkylglycerol, was covalently linked to poly(lactic acid)
      using a carbodiimide cross-linker to form alkylglyceryl-modified dextran-graft
      poly(lactic acid). Solvent displacement and electrospray methods allowed the
      formulation of these materials into nanoparticles having a unimodal size
      distribution profile of about 100-200nm and good stability at physiologically
      relevant pH (7.4). The nanoparticles were characterised in terms of hydrodynamic
      size (by Dynamic Light Scattering and Nanoparticle Tracking Analysis), morphology
      (by Scanning Electron Microscopy and Atomic Force Microscopy) and zeta potential,
      and their toxicity was evaluated using MTT and PrestoBlue assays. Cellular uptake
      was evidenced by confocal microscopy employing nanoparticles that had been loaded
      with the easy-to-detect Rhodamine B fluorescent marker. Transwell-model
      experiments employing mouse (bEnd3) and human (hCMEC/D3) brain endothelial cells
      revealed enhanced permeation (statistically significant for hCMEC/D3) of the
      fluorescent markers in the presence of the nanoparticles. Results of studies
      using Electric Cell Substrate Impedance Sensing suggested a transient decrease of
      the barrier function in an in vitro blood-brain barrier model following
      incubation with these nanoformulations. An in ovo study using 3-day chicken
      embryos indicated the absence of whole-organism acute toxicity effects. The
      collective in vitro data suggest that these alkylglyceryl-modified dextran-graft
      poly(lactic acid) nanoparticles are promising candidates for in vivo evaluations
      that would test their capability to transport therapeutic actives to the brain. 

PMID- 25983314
TI  - Shear wave filtering in naturally-occurring Bouligand structures.
AB  - Wave propagation was investigated in the Bouligand-like structure from within the
      dactyl club of the stomatopod, a crustacean that is known to smash their heavily
      shelled preys with high accelerations. We incorporate the layered nature in a
      unitary material cell through the propagator matrix formalism while the periodic
      nature of the material is considered via Bloch boundary conditions as applied in
      the theory of solid state physics. Our results show that these materials exhibit
      bandgaps at frequencies related to the stress pulse generated by the impact of
      the dactyl club to its prey, and therefore exhibiting wave filtering in addition
      to the already known mechanisms of macroscopic isotropic behavior and toughness. 

PMID- 25983315
TI  - Influence of trace impurities on the in vitro and in vivo degradation of
      biodegradable Mg-5Zn-0.3Ca alloys.
AB  - The hydrogen evolution method and animal experiments were deployed to investigate
      the effect of trace impurity elements on the degradation behavior of high
      strength Mg alloys of type ZX50 (Mg-5Zn-0.3Ca). It is shown that trace impurity
      elements increase the degradation rate, predominantly in the initial period of
      the tests, and also increase the material's susceptibility to localized corrosion
      attack. These effects are explained on the basis of the corrosion potential of
      the intermetallic phases present in the alloys. The Zn-rich phases present in
      ZX50 are nobler than the Mg matrix, and thus act as cathodic sites. The impurity
      elements Fe and Mn in the alloy of conventional purity are incorporated in these
      Zn-rich intermetallic phases and therefore increase their cathodic efficiency. A
      design rule for circumventing the formation of noble intermetallic particles and
      thus avoiding galvanically accelerated dissolution of the Mg matrix is proposed. 

PMID- 25983316
TI  - Microstructure and micromechanics of the heart urchin test from X-ray tomography.
AB  - The microstructure of many echinoid species has long fascinated scientists
      because of its high porosity and outstanding mechanical properties. We have used
      X-ray microtomography to examine the test of Echinocardium cordatum (heart
      urchin), a burrowing cousin of the more commonly known sea urchins. Three
      dimensional imaging demonstrates that the bulk of the test is composed of only
      two distinct, highly porous, fenestrated regions (stereom), in which the
      thickness of the struts is constant. Different degrees of porosity are achieved
      by varying the spacing of the struts. Drawing an analogy to vertebrate trabecular
      bone, where for example, human bone has a connectivity density of ~1/mm(3), we
      measure up to 150,000 strut connections per mm(3). Simulations of mechanical
      loading using finite element calculations indicate that the test performs at very
      close to the optimum expected for foams, highlighting the functional link between
      structure and mechanical properties. 

PMID- 25983317
TI  - Imparting electroactivity to polycaprolactone fibers with heparin-doped
      polypyrrole: Modulation of hemocompatibility and inflammatory responses.
AB  - Hemocompatibility, anti-inflammation and anti-thrombogenicity of acellular
      synthetic vascular grafts remains a challenge in biomaterials design. Using
      electrospun polycaprolactone (PCL) fibers as a template, a coating of polypyrrole
      (PPy) was successfully polymerized onto the fiber surface. The fibers coated with
      heparin-doped PPy (PPy-HEP) demonstrated better electroactivity, lower surface
      resistivity (9-10-fold) and better anti-coagulation response (non-observable
      plasma recalcification after 30min vs. recalcification at 8-9min) as compared to
      fibers coated with pristine PPy. Red blood cell compatibility, measured by%
      hemolysis, was greatly improved on PPy-HEP-coated PCL in comparison to uncoated
      PCL (3.9+/-2.1% vs. 22.1+/-4.1%). PPy-HEP-coated PCL fibers also exhibited higher
      stiffness values (6.8+/-0.9MPa vs. 4.2+/-0.8MPa) as compared to PCL fibers, but
      similar tensile strengths. It was also observed that the application of a low
      alternating current led to a 4-fold reduction of platelet activation (as
      quantitated by CD62p expression) for the PPy-HEP-coated fibers as compared to non
      stimulated conditions. In parallel, a reduction in the leukocyte adhesion to both
      pristine PPy-coated and PPy-HEP-coated fibers was observable with AC stimulation.
      Overall, a new strategy involving the use of hemocompatible conducting polymers
      and electrical stimulation to control thrombogenicity and inflammatory responses
      for synthetic vascular graft designs was demonstrated. 

PMID- 25983318
TI  - Mexican consensus on the diagnosis and management of hepatitis C infection.

PMID- 25983319
TI  - Abscisic acid receptor PYRABACTIN RESISTANCE-LIKE 8, PYL8, is involved in glucose
      response and dark-induced leaf senescence in Arabidopsis.
AB  - Abscisic acid (ABA) receptors in plants are thought to be involved in various
      cellular processes mediated by signal transduction pathways. There are about 14
      ABA receptors in Arabidopsis, but only a few have been studied. In this study, we
      investigated the effect of the disruption and overexpression of an ABA receptor
      gene, PYL8 (At5g53160) on plant responses to glucose (Glc) and dark-induced leaf
      senescence. Expression of PYL8 was strongly reduced by Glc treatment.
      Overexpression of PYL8 in Arabidopsis resulted in significantly reduced seed
      germination and cotyledon greening under high Glc conditions, while RNAi
      transgenic lines were more insensitive to Glc stress. Activities of two Glc
      responsive genes, Arabidopsis thaliana Hexokinase 1 (AtHXK1) and ABA insensitive
      5 (ABI5) were higher in PYL8-overexpressing plants than in the wild-type (WT)
      plants after Glc treatment, whereas the transcript levels of these genes in RNAi
      plants decreased. Furthermore, PYL8-overexpressing plants displayed increased
      yellowing, membrane ion leakage, and reduced chlorophyll content due to dark
      induced senescence, and exhibited stronger expression of a group of senescence
      inducible genes than did WT. The data show that PYL8 plays essential roles in
      responses to both Glc and dark-induced senescence in A. thaliana. 

PMID- 25983320
TI  - An ABC transporter complex encoded by Aluminum Sensitive 3 and NAP3 is required
      for phosphate deficiency responses in Arabidopsis.
AB  - Phosphate is essential for cell metabolism in all organisms. As it is often
      limiting in the soil, plants have evolved various mechanisms to cope with low
      phosphate conditions. Here, we report that Aluminum Sensitive 3 and NAP3, two
      genes previously identified to function in aluminum tolerance, play a critical
      role in plant response to phosphate deficiency. Two T-DNA insertional alleles of
      ALS3 gene in Arabidopsis showed hypersensitive responses to phosphate limiting
      conditions. Compared to the wild type, als3 mutant plants exhibited more severe
      root growth inhibition and developed more root hairs under phosphate starvation.
      Interestingly, these phenotypic changes occurred only when the low-phosphate
      medium is supplemented with sucrose, suggesting that ALS3 regulates low-phosphate
      response in a sugar-dependent manner. Furthermore, NAP3, a gene encoding the
      nucleotide binding domain protein that physically interacts with ALS3, was
      implicated in the same pathway in response to low-P. The nap3 mutant showed the
      same phenotype as the als3 mutant when grown on phosphate depletion medium. We
      conclude that ALS3 and NAP3 protein form an ABC transporter complex that is
      required for sugar-dependent response to phosphate deficiency. 

PMID- 25983321
TI  - Sarcolipin and phospholamban inhibit the calcium pump by populating a similar
      metal ion-free intermediate state.
AB  - We have performed microsecond molecular dynamics (MD) simulations and protein pKa
      calculations of the muscle calcium pump (sarcoplasmic reticulum Ca(2+)-ATPase,
      SERCA) in complex with sarcolipin (SLN) to determine the mechanism by which SLN
      inhibits SERCA. SLN and its close analog phospholamban (PLN) are membrane
      proteins that regulate SERCA by inhibiting Ca(2+) transport in skeletal and
      cardiac muscle. Although SLN and PLB binding to SERCA have different functional
      outcomes on the coupling efficiency of SERCA, both proteins decrease the apparent
      Ca(2+) affinity of the pump, suggesting that SLN and PLB inhibit SERCA by using a
      similar mechanism. Recently, MD simulations showed that PLB inhibits SERCA by
      populating a metal ion-free, partially-protonated E1 state of the pump, E1.
      [Formula: see text] . X-ray crystallography studies at 40-80 mM Mg(2+) have
      proposed that SLN-bound SERCA populates E1.Mg(2+), an intermediate with Mg(2+)
      bound near transport site I. To test this proposed mode of SLN regulation, we
      performed a 0.5-MUs MD simulation of E1.Mg(2+)-SLN in a solution containing 100
      mM K(+) and 3 mM Mg(2+), with calculation of domain dynamics in the cytosolic
      headpiece and side-chain ionization and occupancy in the transport sites. We
      found that SLN increases the distance between residues E771 and D800, thereby
      rendering E1.Mg(2+) incapable of producing a competent Ca(2+) transport site I.
      Following removal of Mg(2+,) a 2-MUs MD simulation of Mg(2+)-free SERCA-SLN
      showed that Mg(2+) does not re-bind to the transport sites, indicating that SERCA
      SLN does not populate E1.Mg(2+) at physiological conditions. Instead, protein pKa
      calculations indicate that SLN stabilizes a metal ion-free SERCA state (E1.
      [Formula: see text] ) protonated at residue E771, but ionized at E309 and D800.
      We conclude that both SLN and PLB inhibit SERCA by populating a similar metal ion
      free intermediate state. We propose that (i) this partially-protonated
      intermediate serves as the consensus mechanism for SERCA inhibition by other
      members of the SERCA regulatory subunit family including myoregulin and
      sarcolamban, and (ii) this consensus mechanism is utilized to regulate Ca(2+)
      transport in skeletal and cardiac muscle, with important implications for
      therapeutic approaches to muscle dystrophy and heart failure.

PMID- 25983322
TI  - TGF-beta induced miR-132 enhances the activation of TGF-beta signaling through
      inhibiting SMAD7 expression in glioma cells.
AB  - Transforming growth factors beta (TGF-beta) pathway has been proven to play
      important roles in oncogenesis and angiogenesis of gliomas. MiR-132 might be
      related to TGF-beta signaling pathway and high miR-132 expression was reported to
      be a biomarker of poor prognosis in patients diagnosed with glioma. However, the
      expression regulation way involved in TGF-beta pathway and clinical significance
      of miR-132 have not been investigated in glioma cells. Here we reported that the
      mRNA level of miR-132 and TGF-beta concentration were both increased in patients
      with brain glioma. Correlation analysis revealed that TGF-beta concentration was
      positively correlated with mRNA level of miR-132. In addition, the mRNA level of
      miR-132 was up-regulated by TGF-beta in a concentration-dependent and time
      dependent manner. Furthermore, we found that miR-132 was involved in modulation
      of the TGF-beta signaling pathway and down-regulation of SMAD7 expression by
      directly targeting the SMAD7 3'-UTR. MiR-132 was negatively correlated with SMAD7
      in patients with brain glioma. Taken together, our results suggest that miR-132
      could be stimulated by TGF-beta and might enhance the activation of TGF-beta
      signaling through inhibiting SMAD7 expression in glioma cells. These findings
      contribute to a better understanding of the mechanism of the activation of TGF
      beta signaling by miR-132. 

PMID- 25983323
TI  - Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1alpha
      expression in C2C12 myotubes.
AB  - Exercise and caloric restriction (CR) have been reported to have anti-ageing,
      anti-obesity, and health-promoting effects. Both interventions increase the level
      of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might
      partially mediate these effects. In addition, it is thought that either 5'
      adenosine monophosphate-activated protein kinase (AMPK) or peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mediates
      the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK
      activity and PGC-1alpha expression remain unclear. Therefore, we explored whether
      DHEA in myotubes acts as an activator of AMPK and increases PGC-1alpha. DHEA
      exposure increased glucose uptake but not the phosphorylation levels of Akt and
      PKCzeta/lambda in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK
      were elevated by DHEA exposure. Finally, we found that DHEA induced the
      expression of the genes PGC-1alpha and GLUT4. Our current results might reveal a
      previously unrecognized physiological role of DHEA; the activation of AMPK and
      the induction of PGC-1alpha by DHEA might mediate its anti-obesity and health
      promoting effects in living organisms. 

PMID- 25983324
TI  - Palmitoleic acid induces the cardiac mitochondrial membrane permeability
      transition despite the presence of L-carnitine.
AB  - Although palmitoleic acid (C16:1) is associated with arrhythmias, and increases
      in an age-dependent matter, the effects of L-carnitine, which is essential for
      the transport of long-chain fatty acids into the mitochondria, are unclear. It
      has been postulated that L-carnitine may attenuate palmitate (C16:0)-induced
      mitochondrial dysfunction and the apoptosis of cardiomyocytes. The aim of this
      study was to elucidate the activity of L-carnitine in the prevention of the
      palmitoleic acid-induced mitochondrial membrane permeability transition and
      cytochrome c release using isolated cardiac mitochondria from rats. Palmitoleoyl
      CoA-induced mitochondrial respiration was not accelerated by L-carnitine
      treatment, and this respiration was slightly inhibited by oligomycin, which is an
      inhibitor of ATP synthase. Despite pretreatment with L-carnitine, the
      mitochondrial membrane potential decreased and mitochondrial swelling was induced
      by palmitoleoyl-CoA. In the presence of a combination of L-carnitine and tiron, a
      free radical scavenger, there was attenuated mitochondrial swelling and
      cytochrome c release following palmitoleoyl-CoA treatment. We concluded that
      palmitoleic acid, but not palmitate, induces the cardiac mitochondrial membrane
      permeability transition despite the presence of L-carnitine.

PMID- 25983325
TI  - Spontaneous and diet-aggravated hemolysis and its correction by probucol in SR-BI
      knockout mice with LDL-R deficiency.
AB  - BACKGROUND: High density lipoprotein receptor SR-BI plays a vital role in
      cholesterol homeostasis. Depletion of SR-BI causes plasma free cholesterol (FC)
      accumulation, which disrupts erythrocytes membrane and might induce hemolytic
      anemia. Here we explored the effects of hypercholesteremia, induced by depletion
      of low density lipoprotein receptor (LDL-R) and high fat diet (HFD) feeding, on
      plasma FC and possible hemolysis in SR-BI knockout (KO) mice, and the therapeutic
      effects of a lipid-lowering drug probucol. METHODS AND RESULTS: To determine the
      effects of LDL-R depletion, SR-BI KO mice were cross-bred with LDL-R KO mice to
      generate SR-BI/LDL-R double KO (dKO) mice. Compared to control wild type (WT), SR
      BI KO and LDL-R KO mice fed normal chow diet (NCD), dKO mice fed NCD had
      increased plasma FC and developed macrocytic anemia, splenomegaly, jaundice and
      renal tubular hemosiderin deposition, indicating spontaneous hemolysis. To
      determine the effects of HFD feeding and probucol therapy, dKO and LDL-R KO mice
      were fed HFD containing 0.5% cholesterol and 20% fat with or without 1% probucol.
      HFD further increased plasma FC and aggravated hemolysis while probucol almost
      normalized plasma FC and corrected hemolysis in dKO mice. CONCLUSION: We
      demonstrated that in SR-BI KO mice, hypercholesteremia due to LDL-R deficiency
      significantly increased plasma FC and induced spontaneous hemolysis, which could
      be further exacerbated by HFD feeding. Probucol almost normalized plasma FC and
      corrected diet-aggravated hemolysis in SR-BI KO mice with LDL-R deficiency.

PMID- 25983326
TI  - Changes in white and brown adipose tissue microRNA expression in cold-induced
      mice.
AB  - There are two classic adipose tissues in mammals, white adipose tissue (WAT) and
      brown adipose tissue (BAT). It has been well known that browning of WAT can be
      induced by cold exposure. In this study, to identify the novel cold responsive
      key miRNAs that are involved in browning, mice were housed at 6  degrees C for 10
      days, and deep sequencing of the miRNAs of WAT and BAT was performed. Our data
      showed that WAT and BAT displayed distinct expression profiles due to their
      different locations, morphology and biological function. A total of 27 BAT and 29
      WAT differentially expressed (DE) miRNAs were identified in response to cold
      stimulation, respectively (fold change >2 and false discovery rate (FDR) <0.05),
      of which, 9 were overlapped in both adipose tissues. Furthermore, the potential
      target genes of the DE miRNAs from BAT and WAT were predicted computationally,
      and the KEGG pathway analysis revealed the enrichment pathways in cold stimulated
      adipose tissues. The expression pattern of miR-144-3p/Bmpr1b/Phlda1 and miR-146a
      5p/Sphk2 were further measured by qPCR. Finally, we found that miR-146a-5p was
      significantly induced during the primary adipogenesis caused by BAT
      differentiation, whereas miR-144-3p was decreased. Our study identifies for the
      first time the novel miRNAs involved in browning of WAT by sequencing and expands
      the therapeutic approaches for combating metabolic diseases.

PMID- 25983327
TI  - Regulation of basal autophagy by transient receptor potential melastatin 7
      (TRPM7) channel.
AB  - Macroautophagy (hereafter referred to as autophagy) is a catabolic process for
      the degradation and recycling of cellular components. Autophagy digests
      intracellular components, recycling material subsequently used for new protein
      synthesis. The Ca(2+)- and Mg(2+)-permeable transient receptor potential
      melastatin 7 (TRPM7) channel underlies the constitutive Ca(2+) influx in some
      cells. Since autophagy is regulated by cytosolic Ca(2+) level, we set out to
      determine whether Ca(2+) influx through the TRPM7 channel regulates basal
      autophagy. When TRPM7 channel expression was induced from HEK293 cells in a
      nutrient-rich condition, LC3-II level increased indicating the increased level of
      basal autophagy. The effect of TRPM7 channel on basal autophagy was via
      Ca(2+)/calmodulin-dependent protein kinase kinase beta, and AMP-activated protein
      kinase pathway. In contrast, the level of basal autophagy was decreased when the
      endogenous TRPM7 channel in SH-SY5Y cells was down-regulated using short hairpin
      RNA. Similarly, an inhibitor for TRPM7 channel decreased the level of basal
      autophagy. In addition, the inhibitory effect of channel inhibitor on basal
      autophagy was reversed by increasing extracellular Ca(2+)concentration,
      suggesting that Ca(2+) influx through TRPM7 channel directly links to basal
      autophagy. Thus, our studies demonstrate the new role of TRPM7 channel-mediated
      Ca(2+) entry in the regulation of basal autophagy. 

PMID- 25983328
TI  - A quality indicator can be biased by intra-hospital heterogeneity: the case for
      quality of patient record keeping in France.
AB  - BACKGROUND: Since 2008, French health institutions providing medical, surgical
      and obstetrical care are assessed on the basis of a set of quality indicators.
      The French National Authority for Health developed a survey design in which 80
      records are randomly selected from each institution. The main aim was to assess
      the effects of internal heterogeneity of a hospital that comprises several units.
      The survey method is based on the hypothesis of intra-institution homogeneity,
      which overlooks the fact that in wide hospitals homogeneity is related to
      departments and thus leads to overall intra-hospital heterogeneity. METHODS:
      Simulated databases were created to modelise the heterogeneity of our hospital
      and computed to assess the reliance of indicator measurement. We used real data
      from a large teaching hospital having internal heterogeneity related to each
      department. RESULTS: Variance under heterogeneity was greater than under
      homogeneity (3- to 18-fold) leading to an increased size of the confidence
      interval (CI) (at 95%) from 9 (given Haute Autorite de Sante sources) to 22 (for
      greatest internal heterogeneity). CONCLUSIONS: The variations in a quality
      indicator can be explained by intra-institution heterogeneity and are not related
      to changes in the quality policy of the hospitals and may lead to errors in terms
      of pay for performance.

PMID- 25983330
TI  - Diagnosis of primary squamous cell carcinoma of the pancreas using endoscopic
      ultrasound-guided core needle biopsy.
AB  - Primary squamous cell carcinoma (SCC) of the pancreas is a particularly rare
      entity. Diagnosis of this tumor is tentatively made after ruling out metastatic
      SCC from another primary site and adenosquamous carcinoma (ASC) of the pancreas.
      Here we discuss the case of a 76-year-old woman who was found to have a solitary
      pancreatic lesion and multiple hepatic lesions. Results of computed tomography
      guided biopsy of the liver lesions were consistent with a metastatic carcinoma
      displaying squamous differentiation; therefore, an endoscopic ultrasound (EUS)
      guided core-needle biopsy (CNB) of the pancreatic mass was performed. Meticulous
      histopathological examination of the pancreatic specimen at multiple levels
      revealed moderately well-differentiated SCC with no glandular component. An
      extensive metastatic work-up did not reveal an extra-pancreatic origin for this
      SCC; hence, a diagnosis of primary SCC of the pancreas was established. To our
      knowledge, this is the first report of the diagnosis of a primary SCC of the
      pancreas using EUS-guided CNB. We believe that CNB has a diagnostic yield
      equivalent to that of fine-needle aspiration for recognizing pancreatic
      adenocarcinoma; however, when cytological examinations reveal atypical squamous
      epithelial cells suggestive of malignancy, CNB may provide a better tissue
      specimen, from which to determine the presence of a glandular component. Such an
      assessment will differentiate pancreatic SCC from ASC.

PMID- 25983329
TI  - Public attitudes towards pricing policies to change health-related behaviours: a
      UK focus group study.
AB  - BACKGROUND: Evidence supports the use of pricing interventions in achieving
      healthier behaviour at population level. The public acceptability of this
      strategy continues to be debated throughout Europe, Australasia and USA. We
      examined public attitudes towards, and beliefs about the acceptability of pricing
      policies to change health-related behaviours in the UK. The study explores what
      underlies ideas of acceptability, and in particular those values and beliefs that
      potentially compete with the evidence presented by policy-makers. METHODS: Twelve
      focus group discussions were held in the London area using a common protocol with
      visual and textual stimuli. Over 300,000 words of verbatim transcript were
      inductively coded and analyzed, and themes extracted using a constant comparative
      method. RESULTS: Attitudes towards pricing policies to change three behaviours
      (smoking, and excessive consumption of alcohol and food) to improve health
      outcomes, were unfavourable and acceptability was low. Three sets of beliefs
      appeared to underpin these attitudes: (i) pricing makes no difference to
      behaviour; (ii) government raises prices to generate income, not to achieve
      healthier behaviour and (iii) government is not trustworthy. These beliefs were
      evident in discussions of all types of health-related behaviour. CONCLUSIONS: The
      low acceptability of pricing interventions to achieve healthier behaviours in
      populations was linked among these responders to a set of beliefs indicating low
      trust in government. Acceptability might be increased if evidence regarding
      effectiveness came from trusted sources seen as independent of government and was
      supported by public involvement and hypothecated taxation.

PMID- 25983331
TI  - One more question to guide the development and implementation of Health in All
      Policies: Integrate?

PMID- 25983332
TI  - Integrating health promotion with quality improvement in a Swedish hospital.
AB  - Integration of workplace employee health promotion (HP) and occupational health
      and safety (OHS) work into organizational quality improvement systems is
      suggested as a way to strengthen HP and OHS activities in an organization. The
      aim of this article was to study what consequences integration of HP, OHS and a
      quality improvement system called kaizen has on the frequency and type of HP and
      OHS activities. A quasi-experimental study design was used where an integration
      of the three systems for HP, OHS respectively kaizen, was performed at six
      intervention units at a Swedish hospital. The remaining six units served as
      controls. Document analysis of all employees' written improvement suggestions
      (kaizen notes) during 2013 was conducted. The findings show that the intervention
      group had more suggestions concerning HP and OHS (n = 114) when compared with the
      control group (n = 78) and a greater variety of HP and OHS suggestions. In
      addition, only the intervention group had included HP aspects. In both groups,
      most kaizen notes with health consideration had a preventive focus rather than
      rehabilitative. The intervention, i.e. the integration of HP, OHS and kaizen
      work, had a favourable effect on HP and OHS work when compared with the controls.
      The results of the study support that this system can work in practice at
      hospitals. 

PMID- 25983333
TI  - Quantification of CatSper1 expression in human spermatozoa and relation to
      functional parameters.
AB  - STUDY QUESTION: Is CatSper1 expression in human spermatozoa related to semen
      parameter values and sperm functions? SUMMARY ANSWER: CatSper1 expression is
      positively related to progressive and hyperactivated (HA) motility, [Ca(2+)]i
      responsiveness to progesterone but not the acrosome reaction (AR). WHAT IS KNOWN
      ALREADY: The role of cationic channel of sperm (CatSper) in sperm functions is
      clear in animal models but less defined in human sperm cells. Current knowledge
      is mostly based on low specificity CatSper inhibitors showing agonistic and toxic
      effects on human spermatozoa and is thus of little help in clarifying the role of
      the CatSper channel in human sperm functions. STUDY DESIGN, SIZE, DURATION:
      CatSper1 protein expression was evaluated in 115 men undergoing semen analysis
      for couple infertility. CatSper1 expression was related to routine semen
      parameters, motility kinematic parameters and basal and progesterone-stimulated
      [Ca(2+)]i and the AR. PARTICIPANTS/MATERIALS, SETTING, METHODS: CatSper1
      expression was evaluated (n = 85 normozoospermic, n = 30 asthenozoospermic
      patients) by immunofluorescence coupled to flow cytometry leading to quantitative
      measurement of the percentage of ejaculated sperm cells expressing the protein.
      Semen analysis was evaluated according to World Health Organization guidelines.
      Kinematic parameters were evaluated by a computer-aided sperm analysis system.
      [Ca(2+)]i was measured by a spectrofluorimetric method in fura-2-loaded
      spermatozoa. The AR was evaluated in live sperm cells by fluorescent-labeled
      lectin. MAIN RESULTS AND THE ROLE OF CHANCE: CatSper1 protein expression in
      spermatozoa was reduced in asthenozoospermic men (mean +/- SD: 53.0 +/- 15.5%, n
      = 30 versus 67.9 +/- 17.1% in normozoospermic, n = 85, P < 0.01) and was
      significantly correlated with progressive (r = 0.36, P < 0.001), total (r = 0.35,
      P < 0.001) and HA (r = 0.41, P < 0.005) motility. In addition to a higher
      percentage of spermatozoa not expressing CatSper1, asthenozoospermic men showed a
      large number of spermatozoa with immunofluorescent signal localized outside the
      principal piece compared with those in normozoospermia. A significant positive
      correlation was found between CatSper1 protein expression and the increase of
      [Ca(2+)]i in response to progesterone (r = 0.36, P < 0.05, n = 40) but not with
      basal [Ca(2+)]i. No correlation was found with the AR, either basal or in
      response to progesterone. LIMITATIONS, REASONS FOR CAUTION: The study is partly
      descriptive. Furthermore, we cannot rule out the possibility that some round
      cells remain after a single round of 40% density gradient centrifugation or that
      this step may have removed some defective or slow swimming sperm, and therefore
      this preparation may not be representative of the entire sperm sample. Although
      our data suggest that CatSper1 may be a useful marker for infertility, and a
      possible contraceptive target, any clinical application is limited without
      further research. WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrate an
      association of CatSper1 expression with human sperm progressive and HA motility
      and provide preliminary evidence that lack of expression or mislocalization of
      CatSper1 in spermatozoa may be involved in the pathogenesis of asthenozoospermia.
      However, mechanistic studies are needed to confirm that the correlations between
      CatSper1 expression and sperm functions are causative. STUDY FUNDING/COMPETING
      INTERESTS: Supported by grants from Ministry of University and Scientific
      Research (PRIN project to E.B. and FIRB project to S.M.) and by Regione Toscana
      (to G.F.). L.T. was recipient of a grant from Accademia dei Lincei (Rome, Italy).
      The authors have no conflicts of interest to declare.

PMID- 25983334
TI  - Measuring Education and Skill.
AB  - This article reviews recent developments in measuring education and skill that
      need to be taken into account in any new initiative to monitor social mobility.
      Over the past half-century, patterns of educational participation and attainment
      have become more heterogeneous, a trend that has been accompanied by increases in
      assessment and testing practices, and the availability of electronic data sources
      and other administrative records, including official school transcripts that are
      generally held indefinitely. This article describes the most promising approaches
      to measuring education and discusses some of the possible challenges for using
      the information to study social mobility. Measures of educational concepts fall
      along at least one of several dimensions: credentials earned, qualities of the
      schools attended, the amount and nature of curricular exposure, and the
      development and acquisition of skills. Selected data sources, with an emphasis on
      school transcripts and administrative records, and their possible uses are
      described.

PMID- 25983335
TI  - Genetic variation in male sexual behaviour in a population of white-footed mice
      in relation to photoperiod.
AB  - In natural populations, genetic variation in seasonal male sexual behaviour could
      affect behavioural ecology and evolution. In a wild-source population of white
      footed mice, Peromyscus leucopus, from Virginia, U.S.A., males experiencing short
      photoperiod show high levels of genetic variation in reproductive organ mass and
      neuroendocrine traits related to fertility. We tested whether males from two
      divergent selection lines, one that strongly suppresses fertility under short
      photoperiod (responder) and one that weakly suppresses fertility under short
      photoperiod (nonresponder), also differ in photoperiod-dependent sexual behaviour
      and responses to female olfactory cues. Under short, but not long, photoperiod,
      there were significant differences between responder and nonresponder males in
      sexual behaviour and likelihood of inseminating a female. Males that were
      severely oligospermic or azoospermic under short photoperiod failed to display
      sexual behaviour in response to an ovariectomized and hormonally primed receptive
      female. However, on the day following testing, females were positive for
      spermatozoa only when paired with a male having a sperm count in the normal range
      for males under long photoperiod. Males from the nonresponder line showed
      accelerated reproductive development under short photoperiod in response to urine
      soiled bedding from females, but males from the responder line did not. The
      results indicate genetic variation in sexual behaviour that is expressed under
      short, but not long, photoperiod, and indicate a potential link between heritable
      neuroendocrine variation and male sexual behaviour. In winter in a natural
      population, this heritable behavioural variation could affect fitness, seasonal
      life history trade-offs and population growth.

PMID- 25983336
TI  - Understanding Farmer Perspectives on Climate Change Adaptation and Mitigation:
      The Roles of Trust in Sources of Climate Information, Climate Change Beliefs, and
      Perceived Risk.
AB  - Agriculture is vulnerable to climate change and a source of greenhouse gases
      (GHGs). Farmers face pressures to adjust agricultural systems to make them more
      resilient in the face of increasingly variable weather (adaptation) and reduce
      GHG production (mitigation). This research examines relationships between Iowa
      farmers' trust in environmental or agricultural interest groups as sources of
      climate information, climate change beliefs, perceived climate risks to
      agriculture, and support for adaptation and mitigation responses. Results
      indicate that beliefs varied with trust, and beliefs in turn had a significant
      direct effect on perceived risks from climate change. Support for adaptation
      varied with perceived risks, while attitudes toward GHG reduction (mitigation)
      were associated predominantly with variation in beliefs. Most farmers were
      supportive of adaptation responses, but few endorsed GHG reduction, suggesting
      that outreach should focus on interventions that have adaptive and mitigative
      properties (e.g., reduced tillage, improved fertilizer management).

PMID- 25983337
TI  - Ontogenetic Change of Signal Brightness in the Foot-Flagging Frog Species
      Staurois parvus and Staurois guttatus.
AB  - Adult individuals of several anuran species exhibit conspicuous visual displays
      during intraspecific communication. While signal properties in adults have been
      subject to an increasing number of studies, little is known about the variation
      of visual signals in juveniles and during ontogenetic changes. Foot-flagging
      signals of the Bornean frogs Staurois guttatus and S. parvus were observed in
      juveniles a few days after metamorphosis. We investigated color parameters of
      foot webbings and body coloration of individuals bred at the Vienna Zoo, and
      their relation to age and body size using spectrophotometry. Our results indicate
      that the brightness of foot webbings of S. guttatus and S. parvus increased with
      increasing age. Additionally, we compared the results with measurements of adult
      individuals from a population in Brunei and discuss possible differences related
      to diet and age as well as the habitat use of juveniles and adults. We suggest
      that the ontogenetic increase in foot-webbing brightness enhances visual
      conspicuousness and the signal-to-noise ratio of the visual signal with sexual
      maturity and potentially functions as cue to the age of the signaler.

PMID- 25983338
TI  - Big fish, little divergence: phylogeography of Lake Tanganyika's giant cichlid,
      Boulengerochromis microlepis.
AB  - The largely endemic cichlid species flocks of the East African Great Lakes are
      among the prime examples for explosive speciation and adaptive radiation.
      Speciation rates differ among cichlid lineages, and the propensity to radiate has
      been linked to intrinsic and extrinsic factors such as sexual selection and
      ecological opportunity. Remarkably, only one cichlid tribe-the Boulengerochromini
      comprises just a single species, Boulengerochromis microlepis, a predominantly
      piscivorous endemic of Lake Tanganyika and the world's largest cichlid. While the
      lineage diverged from its closest relatives at the onset of the Lake Tanganyika
      radiation >8 MYA, mitochondrial control region sequences collected in this study
      dated the most recent common ancestor of B. microlepis to ~60-110 KYA. There was
      no evidence of phylogeographic structure in the lake-wide sample. Patterns of
      genetic diversity and demographic analyses were consistent with slow and steady
      population growth throughout the reconstructed timescale. Additionally, the
      shallow divergence within the species may be related to a possibly large variance
      in reproductive success in this highly fecund species. Trophic niche space
      restriction by sympatric piscivores, lack of geographic structure, low potential
      for sexual selection arising from the monogamous mating system and extinction may
      have contributed to keeping the lineage monotypic.

PMID- 25983339
TI  - Female preferences for male traits and territory characteristics in the cichlid
      fish Tropheus moorii.
AB  - Female mate preferences for male traits and resource characteristics affect trait
      evolution and diversification. Here, we test the effects of male body traits and
      territory characteristics on within-population female preferences and on
      population-assortative mating in the cichlid Tropheus moorii. Within-population
      preferences of females were independent of male body size, coloration and
      territory size but were strongly dependent on territory quality and co-varied
      with male courtship activity. Courtship activity of individual males was
      contingent on the quality of their assigned territory, and therefore, courtship
      may not only indicate intrinsic male quality. On the basis of these results we
      suggest that female preferences for high-quality territories reinforce the
      outcome of malemale competition and ensure male mating success. Mating
      preferences of females for males of their own color variant (ascertained in a
      previous experiment) were not overturned when males of another color variant were
      presented in a superior territory, indicating that within- and between-population
      mate preferences of females depend on different cues.

PMID- 25983340
TI  - A 1.1nW Energy Harvesting System with 544pW Quiescent Power for Next Generation
      Implants.
AB  - This paper presents a nW power management unit (PMU) for an autonomous wireless
      sensor that sustains itself by harvesting energy from the endocochlear potential
      (EP), the 70-100 mV electrochemical bio-potential inside the mammalian ear. Due
      to the anatomical constraints inside the inner ear, the total extractable power
      from the EP is limited to 1.1-6.25 nW. A nW boost converter is used to increase
      the input voltage (30-55 mV) to a higher voltage (0.8 to 1.1 V) usable by CMOS
      circuits in the sensor. A pW Charge Pump circuit is used to minimize the leakage
      in the boost converter. Further, ultra-low-power control circuits consisting of
      digital implementations of input impedance adjustment circuits and Zero Current
      Switching circuits along with Timer and Reference circuits keep the quiescent
      power of the PMU down to 544 pW. The designed boost converter achieves a peak
      power conversion efficiency of 56%. The PMU can sustain itself and a duty-cyled
      ultra-low power load while extracting power from the EP of a live guinea pig. The
      PMU circuits have been implemented on a 0.18um CMOS process.

PMID- 25983341
TI  - An Integration Factor Method for Stochastic and Stiff Reaction-Diffusion Systems.
AB  - Stochastic effects are often present in the biochemical systems involving
      reactions and diffusions. When the reactions are stiff, existing numerical
      methods for stochastic reaction diffusion equations require either very small
      time steps for any explicit schemes or solving large nonlinear systems at each
      time step for the implicit schemes. Here we present a class of semi-implicit
      integration factor methods that treat the diffusion term exactly and reaction
      implicitly for a system of stochastic reaction-diffusion equations. Our linear
      stability analysis shows the advantage of such methods for both small and large
      amplitudes of noise. Direct use of the method to solving several linear and
      nonlinear stochastic reaction-diffusion equations demonstrates good accuracy,
      efficiency, and stability properties. This new class of methods, which are easy
      to implement, will have broader applications in solving stochastic reaction
      diffusion equations arising from models in biology and physical sciences.

PMID- 25983342
TI  - "I Always Kept a Job": Income Generation, Heroin Use and Economic Uncertainty in
      21st Century Detroit.
AB  - This qualitative study, based on a series of 30 in-depth interviews and 109
      economic surveys conducted with active heroin users residing in and around
      Detroit, Michigan, describes reported patterns of heroin use and income
      generation activities. In spite of lack of access to regular, legal employment,
      we found that many participants displayed a dedication to regular daily routine
      and a sense of risk management or control. These findings are discussed relative
      to past research on heroin addiction as well as recent research on the changing
      nature of employment. We argue that this sample fits somewhere in between the
      controlled or working addict, and the "junkie" or "righteous dope fiend" of urban
      lore. We draw a connection between these stable patterns of addiction and income
      generation and the demands of informal and insecure labor markets. Finally, we
      discuss the implications of these findings for further research, interventions,
      and public policy.

PMID- 25983344
TI  - Wealth gradients in early childhood cognitive development in five Latin American
      countries.
AB  - Research from the United States shows that gaps in early cognitive and non
      cognitive ability appear early in the life cycle. Little is known about this
      important question for developing countries. This paper provides new evidence of
      sharp differences in cognitive development by socioeconomic status in early
      childhood for five Latin American countries. To help with comparability, we use
      the same measure of receptive language ability for all five countries. We find
      important differences in development in early childhood across countries, and
      steep socioeconomic gradients within every country. For the three countries where
      we can follow children over time, there are few substantive changes in scores
      once children enter school. Our results are robust to different ways of defining
      socioeconomic status, to different ways of standardizing outcomes, and to
      selective non-response on our measure of cognitive development.

PMID- 25983343
TI  - The Involvement of the T1R3 Receptor Protein in the Control of Glucose Metabolism
      in Mice at Different Levels of Glycemia.
AB  - The heterodimeric protein T1R2/T1R3 is a chemoreceptor mediating taste perception
      of sugars, several amino acids, and non-caloric sweeteners in humans and many
      other vertebrate species. The T1R2 and T1R3 proteins are expressed not only in
      the oral cavity, but also in the intestine, pancreas, liver, adipose tissue, and
      in structures of the central nervous system, which suggests their involvement in
      functions other than gustatory perception. In this study, we analyzed the role of
      the T1R3 protein in regulation of glucose metabolism in experiments with the gene
      knockout mouse strain C57BL/6J-Tas1r3tm1Rfm (Tas1r3-/-), with a deletion of the
      Tas1r3 gene encoding T1R3, and the control strain C57BL/6ByJ with the intact
      gene. Glucose tolerance was measured in euglycemic or food-deprived mice after
      intraperitoneal or intragastric glucose administration. We have shown that in the
      Tas1r3-/- strain, in addition to the disappearance of taste preference for
      sucrose, glucose tolerance is also substantially reduced, and insulin resistance
      is observed. The effect of the Tas1r3 gene knockout on glucose utilization was
      more pronounced in the euglycemic state than after food deprivation. The baseline
      glucose level after food deprivation was lower in the Tas1r3-/- strain than in
      the control strain, which suggests that T1R3 is involved in regulation of
      endogenous glucose production. These data suggest that the T1R3-mediated
      glucoreception interacts with the KATP-dependent mechanisms of regulation of the
      glucose metabolism, and that the main role is likely played by T1R3 expressed in
      the pancreas and possibly in the central nervous system, but not in the
      intestinal mucosa, as it was suggested earlier.

PMID- 25983345
TI  - Polyester textile functionalization through incorporation of pH/thermo-responsive
      microgels. Part II: polyester functionalization and characterization.
AB  - A new approach to functionalize the surface of polyester textiles is described in
      this study. Functionalization was achieved by incorporating pH/temperature
      responsive polyelectrolyte microgels into the textile surface layer using UV
      irradiation. The aim of functionalization was to regulate polyester wettability
      according to ambient conditions by imparting stimuli-responsiveness from the
      microgel to the textile itself. Microgels consisted of pH/thermo-responsive
      microparticles of poly(N-isopropylacrylamide-co-acrylic acid) either alone or
      complexed with the pH-responsive natural polysaccharide chitosan. Scanning
      Electron Microscopy, X-ray Photoelectron Spectroscopy, zeta-potential
      measurements, and topographical analysis were used for surface characterization.
      Wettability of polyester textiles was assessed by dynamic wetting, water vapor
      transfer, and moisture regain measurements. One of the main findings showed that
      the polyester surface was rendered pH-responsive, both in acidic and alkaline pH
      region, owing to the microgel incorporation. With a marked relaxation in their
      structure and an increase in their microporosity, the functionalized textiles
      exhibited higher water vapor transfer rates both at 20 and 40  degrees C, and 65%
      relative humidity compared with the reference polyester. Also, at 40  degrees C,
      i.e., above the microgel Lower Critical Solution Temperature, the functionalized
      polyester textiles had lower moisture regains than the reference. Finally, the
      type of the incorporated microgel affected significantly the polyester total
      absorption times, with an up to 300% increase in one case and an up to 80%
      decrease in another case. These findings are promising for the development of
      functional textile materials with possible applications in biotechnology,
      technical, and protective clothing.

PMID- 25983346
TI  - It's Who You Work With: Effects of Workplace Shares of Nonstandard Employees and
      Women in Japan.
AB  - Previous research on workplace composition has not addressed how the share of
      nonstandard employees affects individual workers' opportunities and well-being.
      Moreover, existing studies generally assume that the effect of a group's
      numerical representation is mediated through the group's relative power and
      status within establishments. This study asks whether workplace composition
      matters when the size of each social group has little impact on its relative
      status. Specifically, I examine the economic and psychological consequences of
      the proportions of nonstandard employees and women in Japanese workplaces, where
      both groups are typically secondary workers who lack power regardless of their
      relative size. The results indicate that working in establishments with modest
      proportions of nonstandard employees enhances individuals' wages and likelihood
      of promotion, but working in those with higher proportions is detrimental.
      Conversely, the greater the share of nonstandard employees in a workplace, the
      more likely all workers are to suffer psychologically. Workplace gender
      composition is also linked to Japanese workers' reported chances of promotion and
      life satisfaction, but it is relevant to fewer worker outcomes than employment
      status composition. This analysis underscores the need to consider workplace
      demography, even if the power and status gaps between different social groups
      vary little with each group's share within establishments. In addition, the
      findings suggest that the global trend of increasing nonstandard work
      arrangements has a more extensive impact on disparities among workers than prior
      research implies.

PMID- 25983347
TI  - Scalable Total Syntheses of (-)-Hapalindole U and (+)-Ambiguine H.
AB  - The Stigonemataceae family of cyanobacteria produces a class of biogenetically
      related indole natural products that include hapalindoles and ambiguines. In this
      full account, a practical route to the tetracyclic hapalindole family is
      presented by way of an eight-step, enantiospecific, protecting-group-free total
      synthesis of (-)-hapalindole U that features an oxidative indole-enolate
      coupling. With gram-scale access to hapalindole U, the first total synthesis of
      an ambiguine alkaloid, (+)-ambiguine H, was completed via an isonitrile-assisted
      prenylation of an indole followed by a photofragmentation cascade.

PMID- 25983348
TI  - Stereochemical evaluation of bis(phosphine) copper catalysts for the asymmetric
      alkylation of 3-bromooxindoles with alpha-arylated malonate esters.
AB  - An improved method for the asymetric alkylation of 3-bromooxindoles with alpha
      arylated malonate esters is described. The asymmetric alkylation demonstrated was
      achieved up to 70% ee utilizing a copper(II) bis(phosphine) complex.

PMID- 25983349
TI  - An approach for the synthesis of nakamuric acid.
AB  - The biosynthesis of dimeric pyrrole-imidazole alkaloids is likely mediated by
      enzyme-catalyzed reversible single-electron transfer (SET) cycloaddition. We now
      show that Ir(ppy)3 can promote SET-mediated formal [2+2] and [4+2] cycloaddition
      reactions of pyrrole-imidazole alkaloids-related substrates under photolytic
      conditions. This biomimetic approach is useful for the construction of the core
      skeleton of nakamuric acid and sceptrin.

PMID- 25983350
TI  - Psychotherapies for Late-Life Depression.

PMID- 25983351
TI  - AGENT-BASED MODELS IN EMPIRICAL SOCIAL RESEARCH.
AB  - Agent-based modeling has become increasingly popular in recent years, but there
      is still no codified set of recommendations or practices for how to use these
      models within a program of empirical research. This article provides ideas and
      practical guidelines drawn from sociology, biology, computer science,
      epidemiology, and statistics. We first discuss the motivations for using agent
      based models in both basic science and policy-oriented social research. Next, we
      provide an overview of methods and strategies for incorporating data on behavior
      and populations into agent-based models, and review techniques for validating and
      testing the sensitivity of agent-based models. We close with suggested directions
      for future research.

PMID- 25983352
TI  - Academic achievement among immigrant and U.S.-born Latino adolescents:
      Associations with cultural, family, and acculturation factors.
AB  - This study examined proximal risk and protective factors that contribute to
      academic achievement among 130 Latino students. Participating students were 56.2%
      female and 35.3% foreign-born (mean age = 11.38, SD = .59). Acculturative stress,
      immigrant status, child gender, parental monitoring, traditional cultural values,
      mainstream values, and English language proficiency were explored in relation to
      academic achievement. Higher levels of parental monitoring, English language
      proficiency, and female gender were associated with higher grades, while
      mainstream values were associated with lower grades. In addition, a significant
      interaction between acculturative stress and immigrant status was found, such
      that higher acculturative stress was related to poorer grades for U.S.-born
      students in particular. Thus, parental monitoring and female gender are potential
      protective factors, while identification with mainstream values and low English
      language proficiency are risk factors for poor grades. U.S.-born students may be
      particularly vulnerable to the effects of acculturative stress.

PMID- 25983353
TI  - The Utility of the YLS/CMI-SV for Assessing Youth Offenders in Singapore.
AB  - The Youth Level of Service/Case Management Inventory-Screening Version (YLS/CMI
      SV) is designed to provide a preliminary estimate of the level of risk for
      antisocial behaviors as well as an indication of areas for intervention in youth
      offenders. This study examined the predictive validity of the YLS/CMI-SV for
      violent, nonviolent, and general recidivism in a sample of 3,264 youth offenders
      within a Singaporean context (Mfollow-up = 1,764.5 days; SDfollow-up = 521.5).
      Cox regression and Receiver Operating Characteristic analyses revealed that the
      YLS/CMI-SV is significantly predictive of general, violent, and nonviolent
      recidivism for the male youth offenders, but there were mixed results for the
      female youth offenders. Overall, these results indicated that the YLS/CMI-SV is a
      useful measure for assessing the levels of risk for male youth offenders, and
      more investigation is needed to determine the suitability of the YLS/CMI-SV for
      the female youth offenders. Its implications for clinical practice and policy are
      discussed.

PMID- 25983354
TI  - Ternary Liquid-Liquid Equilibria for Mixtures of {Ionic Liquid + Thiophene or
      Benzothiophene + Heptane} at T = 308.15 K.
AB  - In this work, the desulfurization ability of alkyl-piperidinium-based and
      phosphonium-based ionic liquids (ILs) for (thiophene or benzothiophene + heptane)
      mixtures are studied. With this aim, ternary liquid-liquid phase equilibrium data
      (LLE) have been obtained for mixtures of {IL (1) + thiophene, or benzothiophene
      (2) + heptane (3)} at T = 308.15 K and p = 101.33 kPa. For this study 1-pentyl-1
      methylpiperidinium bis{(trifluoromethyl)sulfonyl}imide, [C1C5PIP][NTf2], and
      tributylethylphosphonium diethylphosphate, [P2,4,4,4][DEP], were used. The
      suitability of these ILs as solvents for extractive desulfurization has been
      evaluated in terms of the solute distribution ratio and selectivity.
      Immiscibility was observed in the binary liquid systems of (thiophene, or
      benzothiophene + heptane) with both ILs. One of the studied ILs, [C1C5PIP][NTf2],
      shows high distribution ratios and high selectivities for extraction of sulfur
      compounds. The data obtained have been correlated with the non-random two liquid
      NRTL model. The experimental tie-lines and the phase compositions in mole
      fractions in the ternary systems were calculated with an average root mean square
      deviation of 0.0052.

PMID- 25983355
TI  - Patients' Outcome Expectations Matter in Psychological Interventions for Patients
      with Diabetes and Comorbid Depressive Symptoms.
AB  - This study examined whether patients' expectations of treatment outcome predict
      treatment completion, homework compliance, and depressive symptom improvement in
      cognitive behavior therapy (CBT) and mindfulness-based cognitive therapy (MBCT).
      Study participants were patients with diabetes and comorbid depressive symptoms
      who were randomized to 8 sessions of either CBT (n = 45) or MBCT (n = 46), both
      individually delivered. The results showed that high outcome expectations were
      predictive of post-treatment depressive symptoms in CBT and MBCT, but not of
      early and mid-treatment symptoms. Patients' outcome expectations predicted
      treatment completion in CBT and MBCT as well as homework compliance in MBCT.
      Homework compliance did not mediate the association between patients' outcome
      expectations and post-treatment depressive symptom improvement. The findings do
      not support the hypothesis that patients' expectations have an immediate impact
      on patients' mental state and partially support the notion that patients are less
      involved in treatment when they hold low expectations for improvement.

PMID- 25983357
TI  - Rural/Nonrural Differences in College Attendance Patterns.
AB  - Using data from the National Education Longitudinal Study of 1988, this study
      documented college attendance patterns of rural youth in terms of the selectivity
      of first postsecondary institution of attendance, the timing of transition to
      postsecondary education, and the continuity of enrollment. The study also
      examined how these college attendance patterns among rural students differed from
      those among their non-rural counterparts and which factors explained these
      rural/nonrural differences. Results showed that rural youth were less likely than
      their nonrural counterparts to attend a selective institution. In addition, rural
      youth were more likely to delay entry to postsecondary education, compared to
      their urban counterparts. Finally, rural students were less likely than their
      urban counterparts to be continuously enrolled in college. Much of these
      rural/nonrural disparities in college attendance patterns were explained by
      rural/nonrural differences in socioeconomic status and high school preparation.
      Policy implications, limitations of the study, and future research directions are
      also discussed.

PMID- 25983356
TI  - Application and comparison of high-speed countercurrent chromatography and high
      performance liquid chromatography in preparative enantioseparation of alpha
      substitution mandelic acids.
AB  - Preparative enantioseparations of alpha-cyclopentylmandelic acid and alpha
      methylmandelic acid by high-speed countercurrent chromatography (HSCCC) and high
      performance liquid chromatography (HPLC) were compared using hydroxypropy-beta
      cyclodextrin (HP-beta-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) as
      the chiral mobile phase additives. In preparative HPLC the enantioseparation was
      achieved on the ODS C18 reverse phase column with the mobile phase composed of a
      mixture of acetonitrile and 0.10 mol L-1 phosphate buffer at pH 2.68 containing
      20 mmol L-1 HP-beta-CD for alpha-cyclopentylmandelic acid and 20 mmol L-1 SBE
      beta-CD for alpha-methylmandelic acid. The maximum sample size for alpha
      cyclopentylmandelic acid and alpha-methylmandelic acid was only about 10 mg and 5
      mg, respectively. In preparative HSCCC the enantioseparations of these two
      racemates were performed with the two-phase solvent system composed of n-hexane
      methyl tert.-butyl ether-0.1 molL-1 phosphate buffer solution at pH 2.67
      containing 0.1 mol L-1 HP-beta-CD for alpha-cyclopentylmandelic acid (8.5:1.5:10,
      v/v/v) and 0.1 mol L-1 SBE-beta-CD for alpha-methylmandelic acid (3:7:10, v/v/v).
      Under the optimum separation conditions, total 250 mg of racemic alpha
      cyclopentylmandelic acid could be completely enantioseparated by HSCCC with HP
      beta-CD as a chiral mobile phase additive in a single run, yielding 105-110 mg of
      enantiomers with 95-98% purity and 85-90% recovery. But, no complete
      enantioseparation of alpha-methylmandelic acid was achieved by preparative HSCCC
      with either of the chiral selectors due to their limited enantioselectivity. In
      this paper preparative enantioseparation by HSCCC and HPLC was compared from
      various aspects.

PMID- 25983358
TI  - A Dynamic Directional Model for Effective Brain Connectivity using
      Electrocorticographic (ECoG) Time Series.
AB  - We introduce a dynamic directional model (DDM) for studying brain effective
      connectivity based on intracranial electrocorticographic (ECoG) time series. The
      DDM consists of two parts: a set of differential equations describing neuronal
      activity of brain components (state equations), and observation equations linking
      the underlying neuronal states to observed data. When applied to functional MRI
      or EEG data, DDMs usually have complex formulations and thus can accommodate only
      a few regions, due to limitations in spatial resolution and/or temporal
      resolution of these imaging modalities. In contrast, we formulate our model in
      the context of ECoG data. The combined high temporal and spatial resolution of
      ECoG data result in a much simpler DDM, allowing investigation of complex
      connections between many regions. To identify functionally segregated sub
      networks, a form of biologically economical brain networks, we propose the Potts
      model for the DDM parameters. The neuronal states of brain components are
      represented by cubic spline bases and the parameters are estimated by minimizing
      a log-likelihood criterion that combines the state and observation equations. The
      Potts model is converted to the Potts penalty in the penalized regression
      approach to achieve sparsity in parameter estimation, for which a fast iterative
      algorithm is developed. The methods are applied to an auditory ECoG dataset.

PMID- 25983360
TI  - Sex Differences in the Development of Social Relationships in Rhesus Macaques
      (Macaca mulatta).
AB  - Several studies have documented the importance of social bonding for the
      enhancement of individual fitness. However, little is known about how social
      relationships develop through ontogeny, and whether their development follows the
      same trajectory in males and females. Here we analyzed affiliative interactions
      (proximity, social grooming, play) combined with demographic and genetic data in
      semi-free-ranging rhesus macaques (Macaca mulatta) on Cayo Santiago over their
      first 4 yr of life (from birth to sexual maturation) to understand how these
      interactions change through development in both sexes. Generalized linear mixed
      models revealed that social behaviors mostly followed different developmental
      trajectories in males and females and were highly dependent on the social
      context. In particular, sex differences in social behavior varied through
      development depending on the partner's sex and age. Females engaged in more
      social interactions than males, especially with other females, and were more
      involved in grooming around the time of maturation. In contrast, males interacted
      more with males and age peers, especially around maturation. Sex differences in
      social behavior varied through development, but also depended on rank, partner's
      rank, and kin line, although not consistently. High-ranking individuals,
      especially older females, were generally preferred as social partners. Moreover,
      both male and female individuals interacted mostly with maternal kin, although
      males also preferred paternal kin over nonkin. Importantly, most developmental
      changes in sociality happened when individuals were ca. 2 yr old, suggesting that
      this might be a milestone in the development of sociality in rhesus macaques. The
      only notable exception to this pattern was play, which was more pronounced in
      males from the beginning of their lives. We propose that play might serve as a
      trigger of sex differences in social behavior, with sex differences emerging
      early in development and increasing through time as males and females gradually
      grow into their adult social roles.

PMID- 25983361
TI  - Hierarchical Structure of the Eysenck Personality Inventory in a Large Population
      Sample: Goldberg's Trait-Tier Mapping Procedure.
AB  - The structure of the Eysenck Personality Inventory (EPI) is poorly understood,
      and applications have mostly been confined to the broad Neuroticism,
      Extraversion, and Lie scales. Using a hierarchical factoring procedure, we mapped
      the sequential differentiation of EPI scales from broad, molar factors to more
      specific, molecular factors, in a UK population sample of over 6500 persons.
      Replicable facets at the lowest tier of Neuroticism included emotional fragility,
      mood lability, nervous tension, and rumination. The lowest order set of
      replicable Extraversion facets consisted of social dynamism, sociotropy,
      decisiveness, jocularity, social information seeking, and impulsivity. The Lie
      scale consisted of an interpersonal virtue and a behavioral diligence facet.
      Users of the EPI may be well served in some circumstances by considering its
      broad Neuroticism, Extraversion, and Lie scales as multifactorial, a feature that
      was explicitly incorporated into subsequent Eysenck inventories and is consistent
      with other hierarchical trait structures.

PMID- 25983359
TI  - MATERNAL ANXIETY SYMPTOMS AND MOTHER-INFANT SELF- AND INTERACTIVE CONTINGENCY.
AB  - Associations of maternal self-report anxiety-related symptoms with mother-infant
      4-month face-to-face play were investigated in 119 pairs. Attention, affect,
      spatial orientation, and touch were coded from split-screen videotape on a 1-s
      time base. Self- and interactive contingency were assessed by time-series
      methods. Because anxiety symptoms signal emotional dysregulation, we expected to
      find atypical patterns of mother-infant interactive contingencies, and of degree
      of stability/lability within an individual's own rhythms of behavior (self
      contingencies). Consistent with our optimum midrange model, maternal anxiety
      related symptoms biased the interaction toward interactive contingencies that
      were both heightened (vigilant) in some modalities and lowered (withdrawn) in
      others; both may be efforts to adapt to stress. Infant self-contingency was
      lowered ("destabilized") with maternal anxiety symptoms; however, maternal self
      contingency was both lowered in some modalities and heightened (overly stable) in
      others. Interactive contingency patterns were characterized by intermodal
      discrepancies, confusing forms of communication. For example, mothers vigilantly
      monitored infants visually, but withdrew from contingently coordinating with
      infants emotionally, as if mothers were "looking through" them. This picture fits
      descriptions of mothers with anxiety symptoms as overaroused/fearful, leading to
      vigilance, but dealing with their fear through emotional distancing. Infants
      heightened facial affect coordination (vigilance), but dampened vocal affect
      coordination (withdrawal), with mother's face-a pattern of conflict. The maternal
      and infant patterns together generated a mutual ambivalence.

PMID- 25983362
TI  - On Markov Earth Mover's Distance.
AB  - In statistics, pattern recognition and signal processing, it is of utmost
      importance to have an effective and efficient distance to measure the similarity
      between two distributions and sequences. In statistics this is referred to as
      goodness-of-fit problem. Two leading goodness of fit methods are chi-square and
      Kolmogorov-Smirnov distances. The strictly localized nature of these two measures
      hinders their practical utilities in patterns and signals where the sample size
      is usually small. In view of this problem Rubner and colleagues developed the
      earth mover's distance (EMD) to allow for cross-bin moves in evaluating the
      distance between two patterns, which find a broad spectrum of applications. EMD
      L1 was later proposed to reduce the time complexity of EMD from super-cubic by
      one order of magnitude by exploiting the special L1 metric. EMD-hat was developed
      to turn the global EMD to a localized one by discarding long-distance earth
      movements. In this work, we introduce a Markov EMD (MEMD) by treating the source
      and destination nodes absolutely symmetrically. In MEMD, like hat-EMD, the earth
      is only moved locally as dictated by the degree d of neighborhood system. Nodes
      that cannot be matched locally is handled by dummy source and destination nodes.
      By use of this localized network structure, a greedy algorithm that is linear to
      the degree d and number of nodes is then developed to evaluate the MEMD.
      Empirical studies on the use of MEMD on deterministic and statistical synthetic
      sequences and SIFT-based image retrieval suggested encouraging performances.

PMID- 25983363
TI  - Parallel Magnetic Resonance Imaging as Approximation in a Reproducing Kernel
      Hilbert Space.
AB  - In Magnetic Resonance Imaging (MRI) data samples are collected in the spatial
      frequency domain (k-space), typically by time-consuming line-by-line scanning on
      a Cartesian grid. Scans can be accelerated by simultaneous acquisition of data
      using multiple receivers (parallel imaging), and by using more efficient non
      Cartesian sampling schemes. To understand and design k-space sampling patterns, a
      theoretical framework is needed to analyze how well arbitrary sampling patterns
      reconstruct unsampled k-space using receive coil information. As shown here,
      reconstruction from samples at arbitrary locations can be understood as
      approximation of vector-valued functions from the acquired samples and formulated
      using a Reproducing Kernel Hilbert Space (RKHS) with a matrix-valued kernel
      defined by the spatial sensitivities of the receive coils. This establishes a
      formal connection between approximation theory and parallel imaging. Theoretical
      tools from approximation theory can then be used to understand reconstruction in
      k-space and to extend the analysis of the effects of samples selection beyond the
      traditional image-domain g-factor noise analysis to both noise amplification and
      approximation errors in k-space. This is demonstrated with numerical examples.

PMID- 25983364
TI  - Oxidative stress is a potential cost of breeding in male and female northern
      elephant seals.
AB  - The trade-off between current reproductive effort and survival is a key concept
      of life history theory. A variety of studies support the existence of this trade
      off but the underlying physiological mechanisms are not well-understood.
      Oxidative stress has been proposed as a potential mechanism underlying the
      observed inverse relationship between reproductive investment and lifespan.
      Prolonged fasting is associated with oxidative stress including increases in the
      production of reactive oxygen species, oxidative damage and inflammation.Northern
      elephant seals (NES) undergo prolonged fasts while maintaining high metabolic
      rates during breeding. We investigated NES of both sexes to assess oxidative
      stress associated with extended breeding fasts. We measured changes in the plasma
      activity or concentrations of markers for oxidative stress in 30 adult male and
      33 adult female northern elephant seals across their 1-3 month breeding fasts.
      Markers assessed included a pro-oxidant enzyme, several antioxidant enzymes,
      markers for oxidative damage to lipids, proteins and DNA, and markers for
      systemic inflammation.Plasma xanthine oxidase (XO), a pro-oxidant enzyme that
      increases production of oxidative radicals, and several protective antioxidant
      enzymes increased over breeding in both sexes. Males showed increased oxidative
      damage to lipids and DNA and increased systemic inflammation, while oxidative
      damage to proteins declined across breeding. In contrast, females showed no
      oxidative damage to lipids or DNA or changes in inflammation, but showed
      increases in oxidative damage to proteins. XO activity, antioxidant enzymes,
      oxidative damage markers, and inflammatory markers were strongly correlated in
      males but these relationships were weaker or non-existent in females.NES provide
      evidence for oxidative stress as a physiological cost of reproduction in a
      capital breeding mammal. Both sexes strongly up-regulated antioxidant defenses
      during breeding. Despite this response, and in contrast to similar duration non
      breeding fasts in previous studies on conspecifics, there was evidence of
      oxidative damage to tissues. These data demonstrate the utility of using plasma
      markers to examine oxidative stress but also suggest the necessity of measuring a
      broad suite of plasma markers to assess systemic oxidative stress.

PMID- 25983365
TI  - Young Children's Self-Concepts: Associations with Child Temperament, Mothers' and
      Fathers' Parenting, and Triadic Family Interaction.
AB  - This study explored how children's self-concepts were related to child
      temperament, dyadic parenting behavior, and triadic family interaction. At age 3,
      child temperament, mothers' and fathers' parenting behavior, and triadic (mother,
      father, and child) family interaction were observed in the homes of fifty
      families. At age 4, children's self-concepts were assessed using the Children's
      Self-View Questionnaire (Eder, 1990). Analyses revealed that temperamental
      proneness-to-distress and triadic family interaction made independent
      contributions to children's self-reported Timidity and Agreeableness. In
      contrast, dyadic parenting behavior moderated the associations between child
      temperament and children's self-reported Timidity and Agreeableness, such that
      temperament was only associated with children's self-concepts when mothers and
      fathers engaged in particular parenting behaviors. Results suggest both direct
      and interactive influences of family dynamics and child characteristics on
      children's self-concept development.

PMID- 25983366
TI  - Macroscopic Modeling of the singlet oxygen production during PDT.
AB  - Photodynamic therapy (PDT) dose, D, is defined as the absorbed dose by the
      photosensitizer during photodynamic therapy. It is proportional to the product of
      photosensitizer concentration and the light fluence. This quantity can be
      directly characterized during PDT and is considered to be predictive of
      photodynamic efficacy under ample oxygen supply. For type-II photodynamic
      interaction, the cell killing is caused by the reaction of cellular acceptors
      with singlet oxygen. The production of singlet oxygen can be expressed as etaD,
      where eta is the singlet oxygen quantum yield and is a constant under ample
      oxygen supply. For most PDT, it is desirable to also take into account the effect
      of tissue oxygenation. We have modeled the coupled kinetics equation of the
      concentrations of the singlet oxygen, the photosensitizers in ground and triplet
      states, the oxygen, and tissue acceptors along with the diffusion equation
      governing the light transport in turbid medium. We have shown that it is possible
      to express eta as a function of local oxygen concentration during PDT and this
      expression is a good approximation to predict the production of singlet oxygen
      during PDT. Theoretical estimation of the correlation between the tissue oxygen
      concentration and hemoglobin concentration, oxygen saturation, and blood flow is
      presented.

PMID- 25983367
TI  - Reconstruction of optical properties using a diffusion model for interstitial
      diffuse optical tomography.
AB  - An interstitial diffuse optical tomography (iDOT) system with multiple light
      diffusers and isotropic detectors has been developed to characterize the optical
      properties of prostate gland during photodynamic therapy (PDT). During the data
      acquisition, linear or point sources and detectors are inserted into the prostate
      gland, sequentially, and controlled by a motorized system. For our continuous
      wave (CW) iDOT system, CW measurements of optical signal are made, and the
      spatial distributions of light fluence rate can be described by the CW diffusion
      equation. Optical properties (absorption and reduced scattering coefficients) of
      the prostate gland are reconstructed by solving the inverse problem with the use
      of an adjoint model based on the CW diffusion equation. To exam our methodology,
      two and three dimensional mathematical prostate phantoms including anomalies with
      known optical properties is prepared and we compare the absorption and reduced
      scattering images reconstructed for the phantom with the known results. In the
      end, we discuss the issue of reconstruction of optical properties using human
      patient data.

PMID- 25983368
TI  - The design of a robotic multichannel platform for photodynamic therapy.
AB  - A compact robotic platform is designed for simultaneous multichannel motion
      control for light delivery and dosimetry during interstitial photodynamic therapy
      (PDT). Movements of light sources and isotropic detectors are controlled by
      individual motors along different catheters for interstitial PDT. The robotic
      multichannel platform adds feedback control of positioning for up to 16 channels
      compared to the existing dual-motor system, which did not have positioning
      encoders. A 16-channel servo motion controller and micro DC motors, each with
      high resolution optical encoder, are adopted to control the motions of up to 16
      channels independently. Each channel has a resolution of 0.1mm and a speed of
      5cm/s. The robotic platform can perform light delivery and dosimetry
      independently, allowing arbitrary positioning of light sources and detectors in
      each catheter. Up to 16 compact translational channels can be combined according
      to different operational scheme with real-time optimal motion planning. The
      characteristic of high speed and coordinating motion will make it possible to use
      short linear sources (e.g., 1- cm) to deliver uniform PDT treatment to a bulk
      tumor within reasonable time by source stepping optimization of multiple sources
      simultaneously. Advanced robotic control algorithm handles the various unexpected
      circumstance in clinical procedure, e.g., positiontorque/current control will be
      applied to prevent excessive force in the case of resistance in the fiber or
      motorized mechanism. The robotic platform is fully compatible with operation room
      (OR) environment and improves the light delivery and dosimetry in PDT. It can be
      adopted for diffusing optical tomography (DOT), spectroscopic DOT and fluorescent
      spectroscopy.

PMID- 25983369
TI  - A light blanket for intraoperative photodynamic therapy.
AB  - A novel light source - light blanket composed of a series of parallel cylindrical
      diffusing fibers (CDF) is designed to substitute the hand-held point source in
      the PDT treatment of the malignant pleural or intraperitoneal diseases. It
      achieves more uniform light delivery and less operation time in operating room.
      The preliminary experiment was performed for a 9cmx9cm light blanket composed of
      8 9-cm CDFs. The linear diffusers were placed in parallel finger-like pockets.
      The blanket is filled with 0.2 % intralipid scattering medium to improve the
      uniformity of light distribution. 0.3-mm aluminum foil is used to shield and
      reflect the light transmission. The full width of the profile of light
      distribution at half maximum along the perpendicular direction is 7.9cm and 8.1cm
      with no intralipid and with intralipid. The peak value of the light fluence rate
      profiles per input power is 11.7mW/cm2/W and 8.6mW/cm2/W respectively. The
      distribution of light field is scanned using the isotropic detector and the
      motorized platform. The average fluence rate per input power is 8.6 mW/cm2/W and
      the standard deviation is 1.6 mW/cm2/W for the scan in air, 7.4 mW/cm2/W and 1.1
      mW/cm2/W for the scan with the intralipid layer. The average fluence rate per
      input power and the standard deviation are 20.0 mW/cm2/W and 2.6 mW/cm2/W
      respectively in the tissue mimic phantom test. The light blanket design produces
      a reasonably uniform field for effective light coverage and is flexible to
      confirm to anatomic structures in intraoperative PDT. It also has great potential
      value for superficial PDT treatment in clinical application.

PMID- 25983370
TI  - Topical calcitriol prior to photodynamic therapy enhances treatment efficacy in
      non-melanoma skin cancer mouse models.
AB  - Non-melanoma skin cancers (NMSCs) such as basal cell carcinoma (BCC) and squamous
      cell carcinoma (SCC) are the most common form of human cancer worldwide, and
      their incidence is increasing. Photodynamic therapy (PDT), mediated by topically
      applied aminolevulinic acid (ALA) and subsequent exposure to light (either a
      laser or a noncoherent source), is being increasingly used for the treatment of
      dermatological disorders, including BCC and SCC. However, therapeutic responses
      of NMSCs to ALA-PDT are currently not superior to standard therapies, although
      the latter have undesirable side effects including scarring. In this study, we
      report that preconditioning of skin tumors with calcitriol (active form of
      Vitamin D; Vit D) prior to ALA-PDT, significantly improves the treatment outcome.
      In BCC and UVB-induced SCC mouse models, we identified an increase in tumor
      specific accumulation of ALA induced photosensitizer (protoporphyrin IX, PpIX)
      due to Vit D preconditioning, of up to 6-fold in vivo. In addition, increased
      expression of differentiation (145 fold, p < 0.02) and proliferation (42 fold, p
      < 0.005) markers were identified in BCC tumors, all leading to increased tumor
      destruction (18.3 fold, p < 0.03) with the combination approach, as compared to
      ALA-PDT alone. Histomorphological changes identified using hematoxylin and eosin
      staining, and results of TUNEL staining, together documented a beneficial effect
      of Vit D pretreatment upon tumor cell death. We conclude that this new
      combination approach with Vit D and ALA-PDT has great potential to achieve
      complete remission of NMSC tumors, with excellent cosmetic results and an overall
      beneficial impact upon patient care.

PMID- 25983371
TI  - Qualitative and quantitative comparison of colonic microendoscopy image features
      to histopathology.
AB  - Colorectal cancer is the second leading cause of cancer deaths in the United
      States, affecting more than 130,000 Americans every year1. Determining tumor
      margins prior to surgical resection is essential to providing optimal treatment
      and reducing recurrence rates. Colorectal cancer recurrence can occur in up to
      20% of cases, commonly within three years after curative treatment. Typically,
      when colorectal cancers are resected, a margin of normal tissue on both sides of
      the tumor is required. The minimum margin required for colon cancer is 5 cm and
      for the lower rectum 2 cm. However, usually more normal tissue is taken on both
      sides of the tumor because the blood supply to the entire segment is removed with
      the surgery and therefore the entire segment must be removed. Anastomotic
      recurrences may result from inadequate margins. Pathologists look at the margins
      to ensure that there is no residual tumor and this is usually documented in the
      pathology report. We have developed a portable, point-of-care fiber bundle
      microendoscopy imaging system for detection of abnormalities in colonic
      epithelial microstructure. The system comprises a laptop, a modified fiber bundle
      image guide with a 1mm active area diameter and custom Lab VIEW interface, and is
      approved for imaging surgically resected colon tissue at the University of
      Arkansas for Medical Sciences. The microendoscopy probe provides high-resolution
      images of superficial epithelial histology in real-time to assist surgical
      guidance and to localize occult regions of dysplasia which may not be visible.
      Microendoscopy images of freshly resected human colonic epithelium were acquired
      using the microendoscopy device and subsequently mosaicked using custom post
      processing software. Architectural changes in the glands were mapped to
      histopathology H&E slides taken from the precise location of the microendoscopy
      images. Qualitatively, glandular distortion and placement of image guide was used
      to map normal and dysplastic areas of the colonic tumor and surrounding region
      from microendoscopy images to H&E slides. Quantitative metrics for correlating
      images were also explored and were obtained by analyzing glandular diameter and
      spatial distribution as well as image texture.

PMID- 25983372
TI  - Design and validation of a diffuse reflectance and spectroscopic microendoscope
      with poly(dimethylsioxane)-based phantoms.
AB  - Many cases of epithelial cancer originate in basal layers of tissue and are
      initially undetected by conventional microendoscopy techniques. We present a
      bench-top, fiber-bundle microendoscope capable of providing high resolution
      images of surface cell morphology. Additionally, the microendoscope has the
      capability to interrogate deeper into material by using diffuse reflectance and
      broadband diffuse reflectance spectroscopy. The purpose of this multimodal
      technique was to overcome the limitation of microendoscopy techniques that are
      limited to only visualizing morphology at the tissue or cellular level. Using a
      custom fiber optic probe, high resolution surface images were acquired using
      topical proflavine to fluorescently stain non-keratinized epithelia. A 635 nm
      laser coupled to a 200 MUm multimode fiber delivers light to the sample and the
      diffuse reflectance signal was captured by a 1 mm image guide fiber. Finally, a
      tungsten-halogen lamp coupled to a 200 MUm multimode fiber delivers broadband
      light to the sample to acquire spectra at source-detector separations of 374,
      729, and 1051 MUm. To test the instrumentation, a high resolution proflavine
      induced fluorescent image of resected healthy mouse colon was acquired.
      Additionally, five monolayer poly(dimethylsiloxane)-based optical phantoms with
      varying absorption and scattering properties were created to acquire diffuse
      reflectance profiles and broadband spectra.

PMID- 25983373
TI  - Predictive performance of a seven-plex antibody array in prenatal screening for
      Down Syndrome.
AB  - We evaluated the use of multiplex antibody array methodology for simultaneous
      measurement of serum protein markers for first trimester screening of Down
      Syndrome (DS) and other pregnancy outcomes such as preeclampsia. For this
      purpose, we constructed an antibody array for indirect ("sandwich") measurement
      of seven serum proteins: pregnancy-associated plasma protein-A (PAPP-A), free
      beta subunit of human chorionic gonadotropin (fbeta-hCG), alpha-fetoprotein
      (AFP), angiopoietin-like 3 (ANGPTL3), epidermal growth factor (EGF), insulin-like
      growth factor 2 (IGFII), and superoxide dismutase 1 (SOD1). This array was tested
      using 170 DS cases and 510 matched controls drawn during the 8th-13th weeks of
      pregnancy. Data were used for prediction modelling and compared to previously
      obtained AutoDELFIA immunoassay data for PAPP-A and fbeta-hCG. PAPP-A and fbeta
      hCG serum concentrations obtained using antibody arrays were highly correlated
      with AutoDELFIA data. Moreover, DS prediction modeling using (log-MoMmed)
      antibody array and AutoDELFIA data gave comparable results. Of the other markers,
      AFP and IGFII showed significant changes in concentration, although adding these
      markers to a prediction model based on prior risk, PAPP-A and fbeta-hCG did not
      improve the predictive performance. We conclude that implementation of antibody
      arrays in a prenatal screening setting is feasible but will require additional
      first trimester screening markers. 

PMID- 25983374
TI  - Altered chromogranin A circulating levels in Meniere's disease.
AB  - OBJECTIVES: Meniere's disease (MD) is an inner ear disorder characterized by
      episodic vertigo, ear fullness, and hearing loss; usually vertigo attacks cluster
      in specific period. We studied in MD patients the circulating levels of
      chromogranin A (CgA) and vasostatin-1 (VS-1), secreted by the neuroendocrine
      system and involved in the regulation of the endothelial barrier function.
      METHODS: Serum levels were assessed in 37 MD patients and 36 controls. The ratio
      between VS-1 and CgA was calculated. RESULTS: CgA was increased in patients
      compared to controls (1.46 versus 0.67 nM, p = 0.01) while no difference was
      detected for VS-1 (0.41 versus 0.39, resp.). CgA levels in patients positively
      correlated with the frequency of vertigo spells in the previous four weeks (p =
      0.008) and negatively with the time in days from the last vertigo attack (p =
      0.018). Furthermore, the VS-1/CgA ratio negatively correlated with the frequency
      of vertigo spells (p = 0.029) and positively correlated with the time from the
      last attack (p = 0.003). CONCLUSION: The results indicate that variations of CgA
      levels, but not of VS-1, occur in the blood of patients with active MD, depending
      on the frequency of vertigo spells and the time from the last crisis.

PMID- 25983375
TI  - Responsibility without Blame: Therapy, Philosophy, Law.
AB  - I offer a philosophical account of the meaning of responsibility and the meaning
      of blame which shows how it is possible to distinguish them, in theory and in
      practice. Drawing on clinical interventions targeting problematic behaviour in
      service users with personality disorder, I explain why it is essential to
      maintain responsibility and accountability in order to enable learning and
      change, while it is essential to avoid blame. I suggest that the clinical stance
      of Responsibility without Blame be adopted within the criminal justice system, as
      a framework for addressing offending behaviour in a way which serves not only
      justice, but also reform and rehabilitation, by attending to the mental health of
      offenders while yet holding them responsible and to account.

PMID- 25983376
TI  - Observed and Reported Supportive Coparenting as Predictors of Infant-Mother and
      Infant-Father Attachment Security.
AB  - This study examined associations between supportive coparenting and infant-mother
      and infant-father attachment security. Observed and parent-reported coparenting,
      and observed maternal and paternal sensitivity were assessed in a sample of 68
      families with 3.5-month-old infants. Infant-mother and infant-father attachment
      security were assessed in the Strange Situation Procedure (Ainsworth, Blehar,
      Waters, & Wall, 1978) at 12 and 13 months of age, respectively. Observed and
      reported supportive coparenting were associated with greater attachment security
      in the infant-father, but not the infant-mother, attachment relationship. The
      link between observed coparenting and infant-father attachment remained after
      accounting for paternal sensitivity. Furthermore, child gender moderated some
      associations between coparenting and infant-parent attachment security. Among
      families with boys, observed and reported supportive coparenting was related to
      greater infant-mother and infant-father attachment security, respectively.
      Coparenting was unrelated to infant-mother or infant-father attachment security
      among families with girls. Results highlight a possible link between the
      coparental and father-child relationships and the need to consider both parent
      and child gender when examining associations between family functioning and
      attachment.

PMID- 25983377
TI  - Religious Relationships with the Environment in a Tibetan Rural Community:
      Interactions and Contrasts with Popular Notions of Indigenous Environmentalism.
AB  - Representations of Green Tibetans connected to Buddhism and indigenous wisdom
      have been deployed by a variety of actors and persist in popular consciousness.
      Through interviews, participatory mapping and observation, we explored how these
      ideas relate to people's notions about the natural environment in a rural
      community on the Eastern Tibetan plateau, in Sichuan Province, China. We found
      people to be orienting themselves towards the environment by means of three
      interlinked religious notions: (1) local gods and spirits in the landscape, which
      have become the focus of conservation efforts in the form of 'sacred natural
      sites;' (2) sin and karma related to killing animals and plants; (3) Buddhist
      moral precepts especially non-violence. We highlight the gaps between externally
      generated representations and local understandings, but also the dynamic,
      contested and plural nature of local relationships with the environment, which
      have been influenced and reshaped by capitalist development and commodification
      of natural resources, state environmental policies, and Buddhist modernist ideas.

PMID- 25983378
TI  - Opportunities and Challenges for Investigating the Environment-Migration Nexus.
AB  - Environmental change is an acknowledged factor influencing human migration.
      Analytical research regarding the relationship between the environment and human
      migration has increased in recent years yet still faces numerous hurdles, partly
      due to limited availability of suitable data. We review available data and
      methodologies for investigating the environment-migration nexus, identifying data
      inconsistencies resulting from the combination of different sources and
      illustrating the underlying reasons for them. We discuss a number of methods for
      investigating the environment-migration relationship, including frameworks and
      concepts; surveys; empirical, quantitative methods; and simulation approaches.
      Based on this overview, we offer recommendations for improved analyses of the
      environment-migration nexus including reporting data inconsistencies and
      uncertainties, combining approaches and data sources, and developing multiple
      study approaches.

PMID- 25983379
TI  - Resilience in Pre-Columbian Caribbean House-Building: Dialogue Between
      Archaeology and Humanitarian Shelter.
AB  - This paper responds to questions posed by archaeologists and engineers in the
      humanitarian sector about relationships between shelter, disasters and
      resilience. Enabled by an increase in horizontal excavations combined with high
      resolution settlement data from excavations in the Dominican Republic, the paper
      presents a synthesis of Caribbean house data spanning a millennium (1400 BP- 450
      BP). An analysis of architectural traits identify the house as an institution
      that constitutes and catalyses change in an emergent and resilient pathway. The
      "Caribbean architectural mode" emerged in a period of demographic expansion and
      cultural transition, was geographically widespread, different from earlier and
      mainland traditions and endured the hazards of island and coastal ecologies. We
      use archaeological analysis at the house level to consider the historical,
      ecological and regional dimensions of resilience in humanitarian action.

PMID- 25983380
TI  - Moving in groups: how density and unpredictable motion affect predation risk.
AB  - One of the most widely applicable benefits of aggregation is a per capita
      reduction in predation risk. Many factors can contribute to this but, for moving
      groups, an increased difficulty in tracking and targeting one individual amongst
      many has received particular attention. This "confusion effect" has been proposed
      to result from a bottleneck in information processing, a hypothesis supported by
      both modelling and experiment. If the competition for limited attention is
      localised to the particular part of the visual field where the target is located,
      prey density is likely to be the key factor rather than group numbers per se.
      Furthermore, unpredictability of prey movement may enhance confusion, but both
      factors have received insufficient attention from empiricists: undoubtedly
      because of the difficulty of experimental manipulation in natural systems. We
      used a computer-based target tracking task with human subjects to manipulate
      effects of number and density independently, in factorial combination with motion
      path predictability. Density, rather than number, drove the confusion effect in
      our experiment and acted synergistically with the unpredictability of the
      direction of motion. The experimental paradigm we present offers the potential
      for isolating other factors affecting predation success on group-living prey, and
      forging links with the psychological literature on object tracking and visual
      search.

PMID- 25983381
TI  - Brood-partitioning behaviour in unpredictable environments: hedging the bets?
AB  - Spreading reproduction across time or space can optimize fitness by minimizing
      the risks for offspring survival in varying and unpredictable environments.
      Poison frogs (Dendrobatidae) are characterized by complex spatial and
      reproductive behaviour, such as territoriality, prolonged courtship and parental
      care. The partitioning of larvae from terrestrial clutches across several water
      bodies is mainly known from species with carnivorous tadpoles that allocate their
      tadpoles in very small pools, where limited food availability is accompanied by
      an increased risk of cannibalism. However, little is known about the deposition
      behaviour of non-carnivorous species that use medium-sized to large pools. In the
      present study, we investigated whether the Neotropical poison frog Allobates
      femoralis exhibits brood-partitioning behaviour when males transport tadpoles 3
      weeks after oviposition. We sampled 30 artificial water bodies for tadpoles,
      which we genotyped at seven highly polymorphic microsatellite loci. Based on the
      reconstructed pedigree, we show that A. femoralis males distribute larvae of
      single and of successive clutches across several water bodies. The number of
      pools used was significantly associated with the number of clutches per male.
      Ninety-three percent of the males that were assigned to more than one clutch
      spread their tadpoles across several water bodies. Given the highly variable and
      unpredictable biotic and abiotic conditions in tropical rainforest, at the
      spatial scale of the study species' behaviour, we interpret this behaviour as bet
      hedging to improve offspring survival.

PMID- 25983382
TI  - Communication Efficacy and Couples' Cancer Management: Applying a Dyadic
      Appraisal Model.
AB  - The purpose of the present study was to apply Berg and Upchurch's (2007)
      developmental-conceptual model to understand better how couples cope with cancer.
      Specifically, we hypothesized a dyadic appraisal model in which proximal factors
      (relational quality), dyadic appraisal (prognosis uncertainty), and dyadic coping
      (communication efficacy) predicted adjustment (cancer management). The study was
      cross-sectional and included 83 dyads in which one partner had been diagnosed
      with and/or treated for cancer. For both patients and partners, multilevel
      analyses using the actor-partner interdependence model (APIM) indicated that
      proximal contextual factors predicted dyadic appraisal and dyadic coping. Dyadic
      appraisal predicted dyadic coping, which then predicted dyadic adjustment.
      Patients' confidence in their ability to talk about the cancer predicted their
      own cancer management. Partners' confidence predicted their own and the patient's
      ability to cope with cancer, which then predicted patients' perceptions of their
      general health. Implications and future research are discussed.

PMID- 25983383
TI  - Etisus evamuellerae, a new xanthid crab (Decapoda, Brachyura) from the Middle
      Miocene of Austria and Hungary.
AB  - On the basis of several carapaces, a new species of xanthid crab, Etisus
      evamuellerae, is described from the Middle Miocene of the Vienna (Austria) and
      Great Hungarian basins. It differs from the coeval xanthids, Xantho moldavicus
      and Pilodius vulgaris, in having a distinctly protruding front and comparatively
      longer carapace. Contrary to those two species, the new one makes up for just a
      small percentage in the decapod crustacean assemblages studied.

PMID- 25983384
TI  - Harpactoxanthopsis quadrilobata () from the Eocene of Slovakia and Italy: the
      phenomenon of inverted images of fossil heterochelous crabs.
AB  - This short note provides details on a specimen of Harpactoxanthopsis quadrilobata
      (Desmarest, 1822) deposited in the Natural History Museum of Slovak National
      Museum in Bratislava which was figured in the monograph by Lorenthey and Beurlen
      (1929). The phenomenon of inverted images of fossil heterochelous crabs in the
      literature published in the 19th century is documented on the example of H.
      quadrilobata from the Eocene of Italy.

PMID- 25983385
TI  - An advection-based model to increase the temporal resolution of PIV time series.
AB  - A numerical implementation of the advection equation is proposed to increase the
      temporal resolution of PIV time series. The method is based on the principle that
      velocity fluctuations are transported passively, similar to Taylor's hypothesis
      of frozen turbulence. In the present work, the advection model is extended to
      unsteady three-dimensional flows. The main objective of the method is that of
      lowering the requirement on the PIV repetition rate from the Eulerian frequency
      toward the Lagrangian one. The local trajectory of the fluid parcel is obtained
      by forward projection of the instantaneous velocity at the preceding time instant
      and backward projection from the subsequent time step. The trajectories are
      approximated by the instantaneous streamlines, which yields accurate results when
      the amplitude of velocity fluctuations is small with respect to the convective
      motion. The verification is performed with two experiments conducted at temporal
      resolutions significantly higher than that dictated by Nyquist criterion. The
      flow past the trailing edge of a NACA0012 airfoil closely approximates frozen
      turbulence, where the largest ratio between the Lagrangian and Eulerian temporal
      scales is expected. An order of magnitude reduction of the needed acquisition
      frequency is demonstrated by the velocity spectra of super-sampled series. The
      application to three-dimensional data is made with time-resolved tomographic PIV
      measurements of a transitional jet. Here, the 3D advection equation is
      implemented to estimate the fluid trajectories. The reduction in the minimum
      sampling rate by the use of super-sampling in this case is less, due to the fact
      that vortices occurring in the jet shear layer are not well approximated by sole
      advection at large time separation. Both cases reveal that the current
      requirements for time-resolved PIV experiments can be revised when information is
      poured from space to time. An additional favorable effect is observed by the
      analysis in the frequency domain whereby the spectrum becomes significantly less
      prone to aliasing error for the super-sampled data series.

PMID- 25983386
TI  - Performances of motion tracking enhanced Tomo-PIV on turbulent shear flows.
AB  - The motion tracking enhancement technique (MTE) is a recently introduced method
      to improve the accuracy of tomographic PIV measurements at seeding density higher
      than currently practiced. The working principle is based on the fact that the
      particle field and its projections are correlated between the two exposures.
      Therefore, information from subsequent exposures can be shared within the
      tomographic reconstruction process of a single object, which largely reduces the
      energy lost into ghost particles. The study follows a previous work based on
      synthetic particle images, showing that the MTE technique has an effect similar
      to that of increasing the number of cameras. In the present analysis, MTE is
      applied to Tomographic PIV data from two time-resolved experiments on turbulent
      shear flows: a round jet at Re = 5,000 (facq = 1,000 Hz) and a turbulent boundary
      layer at the trailing edge of an airfoil (Rec = 370,000) measured at 12,000 Hz.
      The application of MTE is extended to the case of more than two recordings. The
      performance is assessed comparing the results from a lowered number of cameras
      with respect to the full tomographic imaging system. The analysis of the jet flow
      agrees with the findings of numerical simulations provided the results are scaled
      taking into account the concept of MTE efficiency based on the volume fraction
      where ghost-pairs (Elsinga et al. 2010a) are produced. When a large fraction of
      fluid has uniform motion (stagnant fluid surrounding the jet), only a moderate
      reduction in ghost intensity is expected by MTE. Nevertheless, a visible recovery
      of reconstruction quality is observed for the 3-cameras system when MTE is
      applied making use of 3 recordings. In the turbulent boundary layer, the
      objective is set to increase the seeding density beyond current practice, and the
      experiments are performed at approximately 200,000 particles/megapixel. The
      measurement robustness is monitored with the signal-to-noise ratio S/N for the
      cross-correlation analysis. An estimate of the precision error is obtained for
      the turbulent boundary layer case following the peak height of the spatio
      temporal cross-correlation function (frozen-turbulence). The MTE approach appears
      to be essential for the increase in robustness and measurement precision at such
      seeding density.

PMID- 25983387
TI  - Promoting Health Equity Among LGBT Mid-Life and Older Adults: Revealing how LGBT
      mid-life and older adults can attain their full health potential.

PMID- 25983388
TI  - A Radial Basis Function (RBF)-Finite Difference (FD) Method for Diffusion and
      Reaction-Diffusion Equations on Surfaces.
AB  - In this paper, we present a method based on Radial Basis Function (RBF)-generated
      Finite Differences (FD) for numerically solving diffusion and reaction-diffusion
      equations (PDEs) on closed surfaces embedded in R d . Our method uses a method-of
      lines formulation, in which surface derivatives that appear in the PDEs are
      approximated locally using RBF interpolation. The method requires only scattered
      nodes representing the surface and normal vectors at those scattered nodes. All
      computations use only extrinsic coordinates, thereby avoiding coordinate
      distortions and singularities. We also present an optimization procedure that
      allows for the stabilization of the discrete differential operators generated by
      our RBF-FD method by selecting shape parameters for each stencil that correspond
      to a global target condition number. We show the convergence of our method on two
      surfaces for different stencil sizes, and present applications to nonlinear PDEs
      simulated both on implicit/parametric surfaces and more general surfaces
      represented by point clouds.

PMID- 25983390
TI  - Axioms of adaptivity.
AB  - This paper aims first at a simultaneous axiomatic presentation of the proof of
      optimal convergence rates for adaptive finite element methods and second at some
      refinements of particular questions like the avoidance of (discrete) lower
      bounds, inexact solvers, inhomogeneous boundary data, or the use of equivalent
      error estimators. Solely four axioms guarantee the optimality in terms of the
      error estimators. Compared to the state of the art in the temporary literature,
      the improvements of this article can be summarized as follows: First, a general
      framework is presented which covers the existing literature on optimality of
      adaptive schemes. The abstract analysis covers linear as well as nonlinear
      problems and is independent of the underlying finite element or boundary element
      method. Second, efficiency of the error estimator is neither needed to prove
      convergence nor quasi-optimal convergence behavior of the error estimator. In
      this paper, efficiency exclusively characterizes the approximation classes
      involved in terms of the best-approximation error and data resolution and so the
      upper bound on the optimal marking parameters does not depend on the efficiency
      constant. Third, some general quasi-Galerkin orthogonality is not only
      sufficient, but also necessary for the [Formula: see text]-linear convergence of
      the error estimator, which is a fundamental ingredient in the current quasi
      optimality analysis due to Stevenson 2007. Finally, the general analysis allows
      for equivalent error estimators and inexact solvers as well as different non
      homogeneous and mixed boundary conditions.

PMID- 25983391
TI  - An assessment of the impact of climate adaptation measures to reduce flood risk
      on ecosystem services.
AB  - Measures of climate change adaptation often involve modification of land use and
      land use planning practices. Such changes in land use affect the provision of
      various ecosystem goods and services. Therefore, it is likely that adaptation
      measures may result in synergies and trade-offs between a range of ecosystems
      goods and services. An integrative land use modelling approach is presented to
      assess such impacts for the European Union. A reference scenario accounts for
      current trends in global drivers and includes a number of important policy
      developments that correspond to on-going changes in European policies. The
      reference scenario is compared to a policy scenario in which a range of measures
      is implemented to regulate flood risk and protect soils under conditions of
      climate change. The impacts of the simulated land use dynamics are assessed for
      four key indicators of ecosystem service provision: flood risk, carbon
      sequestration, habitat connectivity and biodiversity. The results indicate a
      large spatial variation in the consequences of the adaptation measures on the
      provisioning of ecosystem services. Synergies are frequently observed at the
      location of the measures itself, whereas trade-offs are found at other locations.
      Reducing land use intensity in specific parts of the catchment may lead to
      increased pressure in other regions, resulting in trade-offs. Consequently, when
      aggregating the results to larger spatial scales the positive and negative
      impacts may be off-set, indicating the need for detailed spatial assessments. The
      modelled results indicate that for a careful planning and evaluation of
      adaptation measures it is needed to consider the trade-offs accounting for the
      negative effects of a measure at locations distant from the actual measure.
      Integrated land use modelling can help land use planning in such complex trade
      off evaluation by providing evidence on synergies and trade-offs between
      ecosystem services, different policy fields and societal demands.

PMID- 25983392
TI  - Combining exploratory scenarios and participatory backcasting: using an agent
      based model in participatory policy design for a multi-functional landscape.
AB  - While the merits of local participatory policy design are widely recognised,
      limited use is made of model-based scenario results to inform such stakeholder
      involvement. In this paper we present the findings of a study using an agent
      based model to help stakeholders consider, discuss and incorporate spatial and
      temporal processes in a backcasting exercise for rural development. The study is
      carried out in the Dutch region called the Achterhoek. Region-specific scenarios
      were constructed based on interviews with local experts. The scenarios are
      simulated in an agent based model incorporating rural residents and farmer
      characteristics, the environment and different policy interventions for realistic
      projection of landscape evolution. Results of the model simulations were
      presented to stakeholders representing different rural sectors at a workshop. The
      results indicate that illustration of the spatial configuration of landscape
      changes is appreciated by stakeholders. Testing stakeholders' solutions by way of
      model simulations revealed that the effectiveness of local interventions is
      strongly related to exogenous processes such as market competition and endogenous
      processes like local willingness to engage in multifunctional activities. The
      integration of multi-agent modelling and participatory backcasting is effective
      as it offers a possibility to initiate discussion between experts and
      stakeholders bringing together different expertise.

PMID- 25983389
TI  - Protein Crystallography from the Perspective of Technology Developments.
AB  - Early on, crystallography was a domain of mineralogy and mathematics and dealt
      mostly with symmetry properties and imaginary crystal lattices. This changed when
      Wilhelm Conrad Rontgen discovered X-rays in 1895, and in 1912 Max von Laue and
      his associates discovered X-ray irradiated salt crystals would produce
      diffraction patterns that could reveal the internal atomic periodicity of the
      crystals. In the same year the father-and-son team, Henry and Lawrence Bragg
      successfully solved the first crystal structure of sodium chloride and the era of
      modern crystallography began. Protein crystallography (PX) started some 20 years
      later with the pioneering work of British crystallographers. In the past 50-60
      years, the achievements of modern crystallography and particularly those in
      protein crystallography have been due to breakthroughs in theoretical and
      technical advancements such as phasing and direct methods; to more powerful X-ray
      sources such as synchrotron radiation (SR); to more sensitive and efficient X-ray
      detectors; to ever faster computers and to improvements in software. The
      exponential development of protein crystallography has been accelerated by the
      invention and applications of recombinant DNA technology that can yield nearly
      any protein of interest in large amounts and with relative ease. Novel methods,
      informatics platforms, and technologies for automation and high-throughput have
      allowed the development of large-scale, high efficiency macromolecular
      crystallography efforts in the field of structural genomics (SG). Very recently,
      the X-ray free-electron laser (XFEL) sources and its applications in protein
      crystallography have shown great potential for revolutionizing the whole field
      again in the near future.

PMID- 25983393
TI  - Nile Red staining of phytoplankton neutral lipids: species-specific fluorescence
      kinetics in various solvents.
AB  - Nile Red (NR) staining potentially offers a simple method for monitoring lipid
      accumulation in microalgal cultivation. However, variable staining efficiencies
      and methods have been reported. The effect of dimethyl sulfoxide (DMSO), ethylene
      glycol (EG) and glycerol on NR penetration with four different phytoplankton
      species representing different taxonomical groups was studied. Treatment with the
      solvents enhanced the NR fluorescence of the diatom Phaeodactylum tricornutum
      during kinetic fluorescence measurements, but high concentrations of solvents
      were needed. None of the solvents improved NR staining of the green alga
      Chlorella pyrenoidosa and Scenedesmus obliquus, which are known to be difficult
      to stain due to their thick and rigid cell walls. The naked Isochrysis sp. cells
      stained best without solvents. The results confirm that NR staining protocol
      needs to be optimized for each species.

PMID- 25983395
TI  - Fire blight resistance of pear genotypes from different European countries.
AB  - Several old cultivars, and breeding clones of European pear Pyrus communis L.
      originating from Belgium, England, Sweden, and Switzerland were evaluated for
      their resistance/susceptibility to fire blight. Studies were carried out during
      three consecutive years 2007-2009 in the greenhouse of Warsaw University of Life
      Sciences, Poland. Strain 691 of Erwinia amylovora was used for artificial
      infection of plants. Genotypes included in this study considerably varied in
      their resistance to fire blight. The most resistant was the old English cultivar
      'Hessle'. The other two genotypes, i.e., 'Granna Rodparon' originating from
      Sweden, and Pyrus communis FG 1606 from Switzerland were included in a group of
      low susceptible ones. The most susceptible were Cra Py H 18, Cra Py V 22 and Cra
      Py W 14 from Belgium.

PMID- 25983394
TI  - Functions and origin of plasmids in Erwinia species that are pathogenic to or
      epiphytically associated with pome fruit trees.
AB  - The genus Erwinia includes plant-associated pathogenic and non-pathogenic
      species. Among them, all species pathogenic to pome fruit trees (E. amylovora, E.
      pyrifoliae, E. piriflorinigrans, Erwinia sp. from Japan) cause similar symptoms,
      but differ in their degrees of aggressiveness, i.e. in symptoms, host range or
      both. The presence of plasmids of similar size, in the range of 30 kb, is a
      common characteristic that they possess. Besides, they share some genetic content
      with high homology in several genes associated with exopolysaccharide production
      and hence, with virulence, as well as in some other genes. Knowledge of the
      content of these plasmids and comparative genetic analyses may provide
      interesting new clues to understanding the origin and evolution of these
      pathogens and the level of symptoms they produce. Furthermore, genetic
      similarities observed among some of the plasmids (and genomes) from the above
      indicated pathogenic species and E. tasmaniensis or E. billingiae, which are
      epiphytic on the same hosts, may reveal associations that could expose the
      mechanisms of origin of pathogens. A summary of the current information on their
      plasmids and the relationships among them is presented here.

PMID- 25983397
TI  - An update on control of brown spot of pear.
AB  - Brown spot of pear is a fungal disease producing high economical losses in
      several pear-growing areas in Europe. Fungicide applications during the growing
      period either at fixed schedule or delivered according to the BSPcast forecasting
      system are not enough to control the disease under favorable conditions. New
      strategies have been introduced to control the inoculum production using
      sanitation methods. These methods are based on combinations of leaf litter
      removal during winter and biological control agent applications during late
      winter, spring and summer. These practices reduce both the inoculum pressure and
      disease levels. Therefore, the resulting optimized disease management consists of
      a combination of sanitation methods applied during the whole year with chemical
      fungicides scheduled according to the BSPcast forecasting model during the
      vegetative period. It is expected that the control of brown spot could be further
      refined upon availability of rapid methods for inoculum potential analysis.
      However, this analysis is difficult due to the variability in pathogenicity
      within the pathogen population.

PMID- 25983396
TI  - Prospects and limitations of microbial pesticides for control of bacterial and
      fungal pomefruit tree diseases.
AB  - The tree constitutes an ecosystem in which microorganisms play an essential role
      in its functionality. Interactions that microorganisms establish with plants may
      be beneficial or detrimental and are of extreme importance in the exploitation of
      trees in agriculture as crop production systems. Fruit trees, especially
      pomefruit trees including apple, pear and several ornamentals are of great
      economic importance but its production is affected by several diseases. Fungal
      and bacterial fruit tree diseases are mainly controlled with chemical fungicides
      and bactericides, but health and environmental concerns about the use of chemical
      pesticides have result in strong regulatory actions and have stimulated the
      development of beneficial microorganisms as microbial pesticides. Up to now,
      several microorganisms have been registered in different countries and in the EU
      as biocontrol agents (BCA) covering mainly fire blight, soil-borne fungal
      diseases and postharvest fruit fungal rot. The key aspects in the success of this
      technology for disease control are related to biosafety and environmental impact
      of biocontrol agents, the traceability and fate in the environment and food
      chain, the improvement by physiological, genetic engineering or the use of
      mixtures or formulations as well as the industrial production and development of
      delivery systems for treatment application to trees.

PMID- 25983398
TI  - Towards an Automated Acoustic Detection System for Free Ranging Elephants.
AB  - The human-elephant conflict is one of the most serious conservation problems in
      Asia and Africa today. The involuntary confrontation of humans and elephants
      claims the lives of many animals and humans every year. A promising approach to
      alleviate this conflict is the development of an acoustic early warning system.
      Such a system requires the robust automated detection of elephant vocalizations
      under unconstrained field conditions. Today, no system exists that fulfills these
      requirements. In this paper, we present a method for the automated detection of
      elephant vocalizations that is robust to the diverse noise sources present in the
      field. We evaluate the method on a dataset recorded under natural field
      conditions to simulate a real-world scenario. The proposed method outperformed
      existing approaches and robustly and accurately detected elephants. It thus can
      form the basis for a future automated early warning system for elephants.
      Furthermore, the method may be a useful tool for scientists in bioacoustics for
      the study of wildlife recordings.

PMID- 25983399
TI  - Discovering independent parameters in complex dynamical systems.
AB  - The transformation of a nonlinear dynamical system into a standard form by using
      one of its variables and its successive derivatives can be used to identify the
      relationships that may exist between the parameters of the original system such
      as the subset of the parameter space over which the dynamics is left invariant.
      We show how the size of the attractor or the time scale (the pseudo-period) can
      be varied without affecting the underlying dynamics. This is demonstrated for the
      Rossler and the Lorenz systems. We also consider the case when two Rossler
      systems are unidirectionally coupled and when a Lorenz system is driven by a
      Rossler system. In both cases, the dynamics of the coupled system is affected.

PMID- 25983400
TI  - Does language do more than communicate emotion?
AB  - Language can certainly communicate emotions, but growing research suggests that
      language also helps constitute emotion by cohering sensations into specific
      perceptions of "anger," "disgust," "fear," etc. The powerful role of language in
      emotion is predicted by a constructionist approach, which suggests that emotions
      occur when sensations are categorized using emotion category knowledge supported
      by language. We discuss the accumulating evidence from social cognitive,
      neuropsychological, cross-cultural, and neuroimaging studies that emotion words
      go beyond communication to help constitute emotional perceptions, and perhaps
      even emotional experiences. We look forward to current directions in research on
      emotional intelligence, emotion regulation, and psychotherapy.

PMID- 25983401
TI  - The educational potential of alcohol-related flushing among Chinese young people.
AB  - : Aim: This paper describes Chinese university students' understanding of the
      meaning of the alcohol-related flushing response and how they reacted to their
      own and someone else's flushing in a group drinking situation. Method: The
      researcher surveyed 530 Chinese university students about their understanding of
      flushing and their perception of how people respond to a person who visibly
      flushes while drinking alcohol. Findings: Most students did not know about the
      physiological cause of flushing. There were significant gender differences in
      both reactions to and perception of responses to a person who flushes. There was
      no direct relationship between flushing and drinking behaviour. CONCLUSIONS: This
      description of flushing behaviour and responses to a flushing person is discussed
      in terms of educational opportunities to change behaviours that could reduce the
      cancer related risks of this visibly at-risk group.

PMID- 25983402
TI  - Management of latent tuberculosis infection: An evidence-based approach.

PMID- 25983403
TI  - The evolution of flexible bronchoscopy: From historical luxury to utter
      necessity!!

PMID- 25983404
TI  - Indications for performing flexible bronchoscopy: Trends over 34 years at a
      tertiary care hospital.
AB  - BACKGROUND AND AIM: Due to its easy maneuverability, patient comfort and
      documented safety as an outpatient procedure, flexible bronchoscopy (FB) has
      replaced rigid bronchoscopy for routine diagnostic use. Herein, we report our 34
      year experience with outpatient performance of FB. MATERIALS AND METHODS: This
      was a retrospective analysis of all FB procedures performed between September
      1979 and November 2013 (period I: 1979-1990; period II: 1991-2000; period III:
      2001-2013) in a tertiary care hospital. Demographic profile of patients,
      indications for performing FB, and annual and seasonal trends were noted from the
      records. RESULTS: A total of 24,814 bronchoscopies were performed during the
      study period. The mean (SD) age of patients (71.6% males) was 48.4 (15.5) years.
      The number of procedures performed per decade showed an absolute increase by
      322%. The most common indication for FB was suspected bronchogenic carcinoma
      (32.2%) followed by pulmonary infections (18.6%) and interstitial lung diseases
      (13%). The proportion of annual cases due to interstitial lung diseases (3.9% in
      period I to 16.2% in period III) increased over the years, whereas disorders such
      as hemoptysis and pleural effusion showed a declining trend as an indication for
      FB. A seasonal trend was observed for diseases such as sarcoidosis, bronchogenic
      carcinoma and pulmonary infections. Six deaths were encountered during the study
      period in patients undergoing FB. CONCLUSION: FB is increasingly being performed
      in the diagnosis of respiratory disorders and is a safe outpatient procedure.
      Although bronchogenic carcinoma remains a common indication for performing FB,
      benign conditions such as pulmonary infections and sarcoidosis constitute
      important indications in the Indian scenario.

PMID- 25983405
TI  - Vascular air embolism after contrast administration on 64 row multiple detector
      computed tomography: A prospective analysis.
AB  - BACKGROUND: Vascular air embolism is being progressively reported as a nonfatal
      event with increase in use of computed tomography (CT) as a diagnostic modality.
      This study was undertaken to study the frequency and site of vascular air
      embolism in patients undergoing contrast-enhanced CT (CECT) and analyze CT
      parameters that influence its prevalence and final outcome. MATERIALS AND
      METHODS: This was a prospective study approved by departmental ethics committee.
      Presence and location of air emboli in 200 patients who underwent CT scan of
      chest on a 64 detector scanner was recorded. We analyzed the role of various
      factors that could influence the prevalence of air embolism after injection of
      contrast in CECT scans. These factors included the amount of contrast injected,
      rate of flow of injection of contrast, site of injection of contrast, and size of
      intravenous access line. RESULTS: Iatrogenic vascular air emboli were seen in 14
      patients (7% of total). The locations of air emboli were main pulmonary artery in
      12 (6% of total), left brachiocephalic vein in 3 (1.5% of total), right atrial
      appendage in 4 (2% of total), and superior vena cava (SVC) in 1 (0.5%) patient.
      There was no association between volume of contrast, flow rate, site and size of
      intravenous access, and presence of air emboli. CONCLUSION: Radiologists as well
      as referring physicians should be aware of vascular air embolism, which can occur
      after contrast injection in patients undergoing CT scan. Age, volume of contrast,
      flow rate of pressure injector, and site and size of venous cannula do not
      influence the likelihood or incidence of detection of venous air emboli on CT
      scans.

PMID- 25983407
TI  - Evaluation of short-term use of nocturnal nasal continuous positive airway
      pressure for a clinical profile and exercise capacity in adult patients with
      obstructive sleep apnea-hypopnea syndrome.
AB  - BACKGROUND AND AIM: The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a
      common chronic respiratory disease, characterized by repetitive complete or
      partial collapse of the upper airway during sleep. The clinical spectrum extends
      between stoppage of breathing, snoring, daytime somnolence, and fatigue, to
      serious cardiovascular disease, stroke, metabolic syndrome, increased morbidity,
      and mortality. We aim to evaluate the short-term use of nasal continuous positive
      airway pressure (nCPAP) therapy for the clinical profile and exercise capacity of
      patients with OSAHS. PATIENT SELECTION: Twenty patients diagnosed with moderate
      to-severe OSAHS were enrolled in the study (study group - 15; clinically and PSG
      matched control group - 5). MATERIALS AND METHODS: Each patient was clinically
      evaluated for sleep-related symptoms, and also assessed with spirometry, the six
      minute walk test (6MWT), and a symptom-limited incremental cardiopulmonary
      exercise test (CPET). The study group patients were administered nCPAP therapy
      for eight hours each night for four weeks, while the control group patients were
      just observed. They were re-assessed after four weeks and the data were
      statistically analyzed between the two groups. RESULTS: The study group patients
      showed a significant (P- < 0.05) improvement in the OSAHS symptoms-the Epworth
      sleepiness score, six-minute walk distance; duration of exercise, power output,
      peak oxygen uptake, anaerobic threshold, diastolic blood pressure, dyspnea, and
      fatigue-in comparison with the control group patients. The improvement in
      exercise capacity following nCPAP therapy was attributed to the relief of
      disabling the OSAHS symptoms and improved cardiovascular, ventilator, and
      musculoskeletal functions. CONCLUSION: All OSAHS patients must be treated with
      nCPAP.

PMID- 25983408
TI  - Correlation of severity of chronic obstructive pulmonary disease with health
      related quality of life and six-minute walk test in a rural hospital of central
      India.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients experience a
      progressive deterioration and disability leading to worsening of their health
      related quality of life (HRQoL) and functional exercise capacity. We performed
      this study to identify the correlation of HRQoL assessed by St George's
      Respiratory Questionnaire (SGRQ) and the functional exercise capacity assessed by
      the six-minute walk test (6MWT) with severity of COPD defined by the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) criteria among spirometry
      confirmed COPD patients, admitted in a tertiary care rural hospital. MATERIALS
      AND METHODS: The study included 129 spirometry-confirmed COPD patients defined by
      the GOLD criteria from a tertiary care hospital in central India. They underwent
      HRQoL measurement using the disease-specific (SGRQ). Functional exercise capacity
      was measured by 6MWT, as per the American Thoracic Society (ATS) guidelines.
      STATISTICAL ANALYSIS: We analyzed the various SGRQ scores and six-minute walk
      distance (6MWD) percentage predicted with various stages of COPD using the
      Student's t-test. The Pearson's correlation coefficient (r) was used to assess
      the relationships between various SGRQ scores and 6MWD with FEV1 % predicted.
      RESULTS: We found that COPD patients with GOLD III and IV, but not GOLD II, had
      significantly poor HRQoL measured by SGRQ, as compared to patients with mild COPD
      (GOLD I). An inverse linear relation was found between 6MWD and the severity of
      COPD. Correlation of FEV1 % predicted with various SGRQ scores varied from - 0.40
      to - 0.53, with a maximum correlation of FEV1 % predicted with an SGRQ symptom
      score (- 0.53) and SGRQ total score (- 0.50). A strong positive correlation was
      found between 6MWD and FEV1 % predicted (0.57). CONCLUSIONS: Staging COPD
      according to the GOLD guidelines does correspond to important differences in the
      HRQoL of COPD patients having severe disease, but not for mild disease, whereas,
      the functional exercise capacity of COPD patients deteriorates in a linear
      fashion with the severity of disease assessed by the GOLD staging criteria.

PMID- 25983406
TI  - A disintegrin and metalloprotease 33 polymorphism association with COPD in long
      term tobacco smokers of the ethnic Kashmiri population of India.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by an
      interaction of various environmental influences especially cigarette smoking and
      genetic determinants. The prevalence of this disease is ever increasing and
      characterization of the genetic determinants of the disease has been undertaken
      globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one
      candidate gene that has been studied. OBJECTIVE: Our objective was to investigate
      whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD
      in long-term tobacco smokers in the ethnic Kashmiri population of northern India.
      MATERIALS AND METHODS: This was a randomized case-control study, which included
      78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex
      matched long-term tobacco smokers (>20 pack years) without any evidence of COPD.
      Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2,
      and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were
      analyzed by descriptive statistics and comparative evaluation was done by
      parametric/non-parametric tests. RESULTS: The analysis of the T1, T2, and Q1
      SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes
      were significantly higher in patients with COPD in comparison with the controls
      (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the
      patients than in the controls (p = 0.177 and 0.43, respectively). CONCLUSION:
      Three SNPs of the ADAM33 gene were significantly associated with COPD in the
      Kashmiri population of India. This study establishes the possible role of ADAM33
      SNPS in the causation of COPD. Further studies across different geographical
      areas in the country will unravel the contribution of this gene in the causation
      of COPD in India.

PMID- 25983409
TI  - Evaluation of the radiological sequelae after treatment completion in new cases
      of pulmonary, pleural, and mediastinal tuberculosis.
AB  - BACKGROUND: Residual radiological lesions may persist even after successful
      treatment of tuberculosis. There is insufficient data as to the nature and
      magnitude of these opacities in the treated cases of tuberculosis. AIMS AND
      OBJECTIVES: This study evaluates the nature and magnitude of residual
      radiological opacities and of complete radiological resolution in new
      successfully treated cases of tuberculosis. DESIGN: Four hundred and forty one
      new cases of pulmonary, pleural or mediastinal tuberculosis were radiologically
      evaluated by chest x-ray, PA view, at the start and end of a successful
      treatment, which was as per the World Health Organization (WHO), Revised National
      Tuberculosis Control Program (RNTCP), and Directly Observed Treatment, Short
      Course (DOTS) guidelines. Patients with a previous history of tuberculosis or
      other lung conditions, treatment failure, retreatment cases, and multidrug
      tuberculosis (MDR-TB) cases were excluded. RESULTS: Residual x-ray lesions were
      seen in 178 cases of tuberculosis (40.36%). Complete radiological resolution was
      seen in 263 cases (59.64%). Of the residual lesions, 67.4% were parenchymal were
      parenchymal in nature, 23.59% were pleural lesions and 8.99% were mediastinal
      lesions. Out of the 126 sputum-positive cases, 70% (n = 88)had residual lesions
      on chest x-ray whereas of the 315 sputum-negative cases 28.5%, (n = 99) had
      radiological residual lesions. CONCLUSION: Residual radiological opacities are
      seen in a large proportion of treated cases of tuberculosis (40%). Pulmonary
      lesions show more residual lesions (67%) than pleural (23%) and mediastinal
      lesions (9%).

PMID- 25983410
TI  - Pulmonary hydatidosis in a tertiary care hospital.
AB  - BACKGROUND: Hydatid disease is caused by the larval stage of Echinococcus. Liver
      is the most commonly involved organ followed by the lungs. Pulmonary hydatidosis
      can be primary or secondary. The disease may be asymptomatic for several years.
      Cause of concern is the fatal anaphylaxis, which may be life threatening.
      MATERIALS AND METHODS: The present retrospective study is over a period of ten
      years (2003-2012). The demographic data including the clinical features,
      radiological findings, other organ involvement, surgical and medical management
      done and histopathological findings were compiled from the records. RESULTS:
      During the study period a total of eight cases, five male and three female, with
      age ranging from eight to 43 years were diagnosed as pulmonary hydatid disease.
      Five patients had presented with complicated cysts. Six patients had solitary
      cysts involving the lung while bilateral lung involvement was seen in two cases.
      One patient had multiple pulmonary cysts. Three patients had associated cysts in
      liver and two in spleen. Surgical lobectomy was done in four cases.
      Histopathology showed acellular laminated ectocysts in all the cases, whereas
      endocyst with brood capsules was seen in five cases. CONCLUSIONS: Pulmonary
      hydatidosis is not uncommon. Anaphylaxis, although rarely seen, may be a
      disastrous event. High index of clinical suspicion and mass awareness for
      interruption of transmission of parasite can lead to proper treatment and
      possible eradication.

PMID- 25983411
TI  - Lung ultrasound: Present and future.
AB  - The scope of lung ultrasound (LUS) in emergency and critical care settings has
      been studied extensively. LUS is easily available at bedside, free of radiation
      hazard and real time. All these features make it useful in reducing need of
      bedside X-rays and CT scan of chest. LUS has been proven to be superior to the
      bedside chest X-ray and equal to chest CT in diagnosing many pleural and lung
      pathologies. The first International Consensus Conference on Lung Ultrasound (ICC
      LUS) has given recommendations for unified approach and language in major six
      areas of LUS. The LUS diagnosis is to be given after integration of findings of
      both lungs. The BLUE protocol is first LUS-based systematic approach in
      diagnosing pleural and lung pathologies. The protocol suggested in this article
      includes history and conventional clinical assessment along with LUS features. 

PMID- 25983412
TI  - Miliary tuberculosis disease complicated by Pott's abscess in an infant: Seven
      year follow-up.
AB  - A 20-month-old boy presented with 1-year history of persistent fever, cough, and
      progressive abdominal distention. Abdominal ultrasonography showed hepatomegaly
      and multiple calcifications in the liver and spleen. Thoracic computed tomography
      showed multiple mediastinal lymph nodes and consolidation in both lungs.
      Additionally, there was a 2-cm thick retroperitoneal soft tissue mass destroying
      the T7-8 and L1-L2 vertebral bodies. The patient was preliminarily diagnosed with
      miliary tuberculosis (TB) and Pott's disease, and began administering anti-TB
      treatment consisting of isoniazid, rifampin, ethambutol, and pyrazinamide. Acid
      resistant bacilli analysis and mycobacterial culture of the biopsy specimen of
      Pott's abscess were positive. Mycobacterial culture and PCR of gastric aspirate
      were also positive. The patient's condition progressively improved with anti-TB
      treatment and he received 12 months of antiTB therapy. At the end of the
      treatment all of the patient's symptoms were relieved and he was well except for
      kyphosis. Miliary TB complicated by Pott's abscess is a very rare presentation of
      childhood TB. The presented case shows that when Pott's abscess is diagnosed and
      surgically corrected without delay, patients can recover without squeal. 

PMID- 25983413
TI  - Retropharyngeal abscess as a rare presentation of pulmonary tuberculosis.
AB  - A tubercular retropharyngeal abscess is rare in immunocompetent adults. In the
      case of a tubercular retropharyngeal abscess, it is usually due to cervical spine
      tuberculosis and is seen mostly in children. A 19-year-old female patient
      presented to our Medicine Outpatient Department (OPD) at All India Institute of
      Medical Sciences (AIIMS) with odynophagia and neck pain for two months, without
      any other constitutional symptoms. On evaluation, she was diagnosed with
      tubercular retropharyngeal abscess along with pulmonary tuberculosis, without
      involvement of the cervical spine. This patient was successfully treated by
      antituberculosis drug therapy alone, without any need for surgical drainage. 

PMID- 25983414
TI  - Paragonimus westermani infection in lung: A confounding diagnostic entity.
AB  - Paragonimiasis is a food-borne parasitic zoonosis caused by the genus
      Paragonimus. Fresh water snails, crabs, and crayfish are the first and second
      intermediate hosts, respectively. Humans acquire this infection by ingesting
      uncooked/undercooked crustaceans. Laboratory diagnosis of Paragonimiasis is done
      by demonstration of ova in the sputum/feces/pleural fluid or by serology. A case
      of pulmonary Paragonimiasis is presented herewith; the patient having been
      diagnosed with pulmonary tuberculosis earlier. The aim of this presentation is to
      highlight this entity so that it is considered in the differential diagnosis in a
      case of hemoptysis. 

PMID- 25983416
TI  - Tracheal schwannoma: Completely resected with therapeutic bronchoscopic
      techniques.
AB  - Tracheal schwannomas are rare benign tumors of the trachea. There are only a few
      reported cases in the literature. Surgeons have generally resected these tumors,
      whereas bronchoscopists have attempted to remove them bronchoscopically. We
      report a case of tracheal schwannoma which was completely resected using
      bronchoscopic techniques. 

PMID- 25983415
TI  - Laryngeal metastasis from lung cancer.
AB  - Metastatic tumors of the larynx are rare. The most common tumors metastasizing to
      the larynx are melanoma and renal cell carcinoma. Bronchogenic carcinoma
      metastasizing to the larynx has been rarely described. Herein, we report the case
      of a 49-year-old, chronic smoker, who incidentally had a laryngeal growth
      detected during flexible bronchoscopy examination for evaluation of suspected
      lung cancer. Histopathological examination of the laryngeal nodule and the biopsy
      obtained from the main bronchus growth confirmed the diagnosis of metastatic
      squamous cell carcinoma to the larynx from primary lung cancer. 

PMID- 25983417
TI  - Right ventricular thrombus with pulmonary artery aneurysm in a young male: A rare
      presentation of Behcet's disease.
AB  - We describe an adolescent patient presenting with hemoptysis. Detailed clinical
      work up of the patient showed right ventricular thrombus and bilateral pulmonary
      artery aneurysms along with the prescribed criteria for the diagnosis of Behcet's
      disease. Younger age of the patient was another distinctive feature of this case.
      Six months of therapy with cyclophosphamide and prednisolone resulted in near
      complete clinicoradiological response. 

PMID- 25983418
TI  - A rare bronchial anomaly presenting as a paracardiac mass.
AB  - Abnormal bronchi arising from trachea and main bronchi are rare and usually
      clinically silent. These bronchial variations, however, pose a significant
      diagnostic challenge related to their variable presentation and perhaps the low
      level of awareness among clinicians and radiologists. Complications including
      recurrent infections, hemoptysis, and rarely malignancies may arise, if the
      diagnosis is delayed. We came across a patient with chronic cough in whom
      endoscopic and imaging evaluation, including fine-needle aspiration cytology
      (FNAC), proved non-diagnostic. Thorough evaluation of multidetector computed
      tomography (MDCT) performed in our department, however, revealed an accessory
      cardiac bronchus with rudimentary lung parenchyma in the paracardiac location.
      This case highlights the importance of meticulous airway evaluation on MDCT in
      all patients referred with respiratory symptoms. 

PMID- 25983419
TI  - Pleuropulmonary blastoma in adolescence: A rare tumor beyond first decade of
      life.
AB  - Pleuropulmonary blastoma (PPB) is a unique dysontogenetic and a primitive
      neoplasm occuring almost exclusively in the first decade of life, as a pulmonary-
      and/or pleural-based tumor with cystic, solid, or combined cystic and solid
      features. It is characterized histologically by a primitive, variably mixed
      blastematous and sarcomatous tissues. These tumors are usually associated with a
      poor prognosis. However, with a multimodality treatment approach, the survival of
      the patient can be prolonged. We herein report two cases of PPB in adolescence, a
      rare presentation beyond first decade of life with a short review of literature. 

PMID- 25983420
TI  - EUS-B-FNA: Pulmonologist's viewpoint: Whose tube is it anyway?

PMID- 25983421
TI  - Aberrant arterial supply to left lung.

PMID- 25983422
TI  - Eluding normal variant.

PMID- 25983423
TI  - Case report: Non-small-cell lung carcinoma presenting as a foot swelling.

PMID- 25983424
TI  - Necrotic mediastinal lymph node enlargement in a middle-aged female.

PMID- 25983425
TI  - Unusual presentation of pulmonary nocardiosis as pyopneumothorax in HIV.

PMID- 25983426
TI  - Right bronchial artery from left common carotid artery: A rare anomalous origin.

PMID- 25983427
TI  - A rare case of dengue and H1N1 co-infection: A deadly duo.

PMID- 25983429
TI  - Different fractionation regimes in palliative thoracic radiotherapy: Some facets.

PMID- 25983428
TI  - Cannon-ball pulmonary metastases as a presenting feature of stomach cancer.

PMID- 25983430
TI  - Urinary neutrophil gelatinase-associated lipocalin in critically ill surgical
      cancer patients.
AB  - BACKGROUND AND AIMS: Neutrophil gelatinase-associated lipocalin (N-GAL) is an
      early biomarker of acute kidney injury (AKI) due to various etiologies. On the
      other hand, N-GAL is also elevated in patients with acute inflammatory conditions
      and in several solid neoplasms. The goal of this study was to assess the efficacy
      of N-GAL as a predictor of AKI and mortality in oncological surgical patients
      postoperatively in the intensive care unit (ICU). METHODS: This was a prospective
      cohort observation study on adult cancer patients submitted to elective or
      emergency surgeries and admitted in the ICU. Urinary N-GAL was measured at the
      first 2 h after admission. AKI incidence and other complications were assessed,
      including hospital mortality. RESULTS: A total of 22 patients were assessed (77%
      male, age 52.8 years, Acute Physiology and Chronic Health Evaluation II [APACHE
      II] 17.3) in whom the most frequent site of cancer was the gastrointestinal
      tract. AKI incidence was 13.6%. Urinary N-GAL was a predictor of AKI (22.0 ng/ml
      in patients without AKI vs. 239.1 ng/ml in patients with AKI, P < 0.001).
      Multivariate analysis showed that the main predictors of AKI were age, APACHE II,
      and N-GAL. N-GAL was also higher, although not statistically significant in
      patients who died in the hospital. CONCLUSIONS: In oncological postoperative
      patients admitted to the ICU, urinary N-GAL was an independent predictor of AKI;
      moreover, its level was higher in the deceased patients.

PMID- 25983431
TI  - Stress levels of critical care doctors in India: A national survey.
AB  - BACKGROUND: Doctors working in critical care units are prone to higher stress due
      to various factors such as higher mortality and morbidity, demanding service
      conditions and need for higher knowledge and technical skill. AIM: The aim was to
      evaluate the stress level and the causative stressors in doctors working in
      critical care units in India. MATERIALS AND METHODS: A two modality questionnaire
      based cross-sectional survey was conducted. In manual mode, randomly selected
      delegates attending the annual congress of Indian Society of Critical Care
      Medicine filled the questionnaire. In the electronic mode, the questionnaires
      were E-mailed to critical care doctors. These questionnaires were based on
      General Health Questionnaire-12 (GHQ-12). Completely filled 242 responses were
      utilized for comparative and correlation analysis. RESULTS: Prevalence of
      moderate to severe stress level was 40% with a mean score of 2 on GHQ-12 scale.
      Too much responsibility at times and managing VIP patients ranked as the top two
      stressors studied, while the difficult relationship with colleagues and sexual
      harassment were the least. Intensivists were spending longest hours in the
      Intensive Care Unit (ICU) followed by pulmonologists and anesthetists. The mean
      number of ICU bed critical care doctors entrusted with was 13.2 +/- 6.3.
      Substance abuse to relieve stress was reported as alcohol (21%), anxiolytic or
      antidepressants (18%) and smoking (14%). CONCLUSION: Despite the higher workload,
      stress levels measured in our survey in Indian critical care doctors were lower
      compared to International data. Substantiation of this data through a wider study
      and broad-based measures to improve the quality of critical care units and
      quality of the lives of these doctors is the need of the hour.

PMID- 25983432
TI  - Problems and limitations in thrombolysis of acute stroke patients at a tertiary
      care center.
AB  - AIM: (1) To evaluate the number of patients thrombolysed within 1 h of arrival to
      emergency room (ER) (2) To identify reasons for delay in thrombolysis of acute
      stroke patients. MATERIALS AND METHODS: All patients admitted to ER with symptoms
      suggestive of stroke from January 2011 to November 2013 were studied.
      Retrospective data were collected to evaluate ER to needle (door to needle time
      [DTNt]) time and reasons for delay in thrombolysis. The parameters studied (1)
      onset of symptoms to ER time, (2) ER to imaging time (door to imaging time
      [DTIt]), (4) ER to needle time (door to needle) and (5) contraindications for
      thrombolysis. RESULTS: A total of 695 patients with suspected stroke were
      admitted during study period. 547 (78%) patients were out of window period. 148
      patients (21%, M = 104, F = 44) arrived within window period (<4.5 h.). 104
      (70.27%) were contraindicated for thrombolysis. Majority were intracerebral
      bleeds. 44 (29.7%) were eligible for thrombolysis. 7 (15.9%) were thrombolysed
      within 1 h. The mean time for arrival of patients from onset of symptoms to
      hospital (symptom to door) 83 min (median - 47). The mean door to neuro-physician
      time (DTPt) was 32 min (median - 15 min). The mean DTIt was 58 min (median - 50
      min). The mean DTNt 104 (median - 100 min). CONCLUSION: Reasons for delay in
      thrombolysis are: Absence of stroke education program for common people. Lack of
      priority for triage and imaging for stroke patients.

PMID- 25983433
TI  - Metabolic acidosis during parenteral nutrition: Pathophysiological mechanisms.
AB  - Total parenteral nutrition (TPN) is associated with metabolic complications
      including metabolic acidosis (MA), one of the main disorders of acid-base
      balance. The main causes involved in the appearance of MA during TPN
      administration are the metabolism of cationic amino acids and amino acids
      containing sulfuric acid (exogenous addition), the titratable acidity of the
      infused parenteral solution, the addition of acidificant agents (hydrochloric
      acid, acetic acid), thiamine deficiency, disruption of carbohydrate and lipid
      metabolic pathways and D-fructose administration. Moreover, hypophosphatemia that
      appears during TPN therapy contributes significantly to the maintenance of MA.
      This review describes in a comprehensive way the pathophysiological mechanisms
      involved in the appearance of MA induced by intravenous administration of TPN
      products most commonly used in critically ill-patients. 

PMID- 25983434
TI  - Complications during the management of pediatric refractory status epilepticus
      with benzodiazepine and pentobarbital infusions.
AB  - The objective of this retrospective study was to evaluate complications in the
      management of refractory status epilepticus (RSE) treated with benzodiazepine and
      pentobarbital infusions. Of 28 children with RSE, eleven (39%) were treated with
      a pentobarbital infusion after failure to control RSE with a benzodiazepine
      infusion; while17 children (61%) required only a benzodiazepine infusion. The
      mean maximum pentobarbital infusion dosage was 5.2 +/- 1.8 mg/kg/h. Twenty-five
      patients received a continuous midazolam infusion with an average dosage of 0.41
      +/- 0.43 mg/kg/h. The median length of stay was longer for the pentobarbital
      group. Children requiring pentobarbital therapy were more likely to develop
      hypotension, require inotropic support, need intubation, mechanical ventilation,
      peripheral nutrition, and blood products; furthermore, they were more likely to
      develop hypertension and movement disorder after or during weaning. In
      conclusion, children with RSE who required pentobarbital therapy had a longer
      hospital stay with more complications. 

PMID- 25983435
TI  - How we managed a difficult to ventilate patient.
AB  - A 40-year-old female presented with respiratory difficulty, cough and sputum with
      blood streaking. Her right lung was destroyed, and trachea was shifted to the
      same side. On mechanical ventilation, she developed hypoxia and rise in blood
      pressure. Ventilator was not delivering set tidal volume. After looking into the
      cause, it was decided to reintubate the patient with new endotracheal tube after
      cutting bevel. Thereafter, there was successful ventilation. 

PMID- 25983436
TI  - Acute concentrated phenol dermal burns: Complications and management.
AB  - Phenol burns can result in multiple organ failure. This is a case report of acute
      severe phenol dermal burn after accidental splash of 94% phenol on 35-year-old
      patient's body who was brought to hospital after 90 min of exposure.
      Decontamination was done with high-density water and glycerol. Early
      complications in form of metabolic acidosis and acute renal failure required
      hemodialysis. Extensive protein denaturation was managed with IV albumin and high
      protein diet. Patient also developed pleural effusion and acute respiratory
      distress syndrome, but these were successfully managed by intercostal drain tube
      insertion and noninvasive ventilation. The patient survived after multiple organ
      failures and widespread burns despite the fact that it has been observed that
      outcome of phenol burns with >60(2) inches of skin affected or two or more organs
      failure involving renal system is nearly fatal. 

PMID- 25983437
TI  - Intravenous ketamine for treatment of super-refractory convulsive status
      epilepticus with septic shock: A report of two cases.
AB  - Refractory and super-refractory status epilepticus is a life-threatening
      neurological emergency, associated with high morbidity and mortality. Treatment
      should be aimed to stop seizure and to avoid cerebral damage and another
      morbidity. Published data about effectiveness, safety and outcome of various
      therapies and treatment approaches are sparse and are mainly based on small case
      series and retrospective data. Here we report successful management of two cases
      of super-refractory status epilepticus refractory to anesthetic therapy with
      midazolam and complicated by septic shock, managed successfully with ketamine
      infusion. 

PMID- 25983438
TI  - Extra corporeal carbon dioxide removal: A reliable modality in refractory
      hypercapnia to prevent invasive ventilation.
AB  - Extracorporeal carbon dioxide removal (ECCO2R) is a valid alternative to consider
      in hypercapnic respiratory failure in chronic obstructive pulmonary disease
      (COPD) patients to avoid invasive ventilation when noninvasive ventilation fails.
      Here we report a similar case, after obtaining informed consent, where a patient
      suffering from severe hypercapnic respiratory failure due to COPD, was selected
      for ECCO2R and improved remarkably. 

PMID- 25983439
TI  - Catastrophic antiphospholipid syndrome (CAPS): A rare and fatal encounter.

PMID- 25983440
TI  - Bilateral symmetrical digital gangrene of upper and lower limbs due to purpura
      fulminans caused by Streptococcus pyogenes: A rare entity.

PMID- 25983441
TI  - Congenital lobar emphysema: Intubation and ventilation strategies.

PMID- 25983442
TI  - Methylmalonic acidemia and diabetic ketoacidosis: An unusual association.

PMID- 25983443
TI  - Mortality patterns among critically ill children in a pediatric intensive care
      unit of a developing country.

PMID- 25983444
TI  - Comments on "Candida glabrata candidemia; an emerging threat in critically ill
      patients".

PMID- 25983445
TI  - Antimicrobial dosing in critically ill patients with sepsis-induced acute kidney
      injury.

PMID- 25983446
TI  - CytoSorb-friend or foe!!

PMID- 25983447
TI  - Delhi orthopaedic association 2009-2012.

PMID- 25983448
TI  - Emerging technologies in orthopaedics: Are we ready for the challenge?

PMID- 25983449
TI  - Current concepts in surgical treatment of osteosarcoma.
AB  - Osteosarcoma is the most common malignant primary neoplasm of bone. For an
      optimal oncological outcome, surgical removal of tumor is an essential component
      of its multidisciplinary treatment. Limb salvage surgery has long been
      established as the standard of care for osteosarcoma. While limb-salvaging
      techniques have acceptable rates of disease control, amputation remains a valid
      procedure in selected cases. In current orthopedic oncology practice, the focus
      is on optimizing the balance between preservation of form and function of the
      limb and adequate oncological clearance at the same time. Improving the
      functional outcome and longevity of reconstructive procedures also remains a
      challenge. 

PMID- 25983450
TI  - Risk factors and diagnosis of developmental dysplasia of hip in children.
AB  - Developmental dysplasia of hip (DDH) is one entity one occasionally comes across
      while in a busy orthopaedic or paediatric outpatient department. The knowledge of
      risk factors and awareness of the condition is must for every orthopaedic surgeon
      and paediatrician as well lest the diagnosis will be missed. An early diagnosis
      can alter the prognosis of the disease and prevent late disabilities. 

PMID- 25983451
TI  - Proximal femoral fractures: Principles of management and review of literature.
AB  - The purpose of this study was to review the principles involved in the management
      of proximal femoral fractures as reported in the literature. METHODS: A medical
      literature search in the MEDLINE (PubMed) and Cochrane database was undertaken to
      review strategies and principles in proximal femoral fracture treatment.
      Randomized control trials and meta analysis were given preference while case
      reports/small series were rejected. RESULTS AND CONCLUSIONS: Early anatomical
      reduction and surgical fixation remains the best option to reduce the risk of
      complications like non-union and avascular necrosis in treating fracture neck
      femurs. Cancellous screws continue to be the preferred treatment for fixation of
      neck femur fractures in younger population until the benefit of using sliding hip
      screws is validated by large multicentric studies. In the geriatric age group,
      early prosthetic replacement brings down the mortality and morbidity associated
      with neck femur fractures. Sliding hip screw (DHS) is the best available option
      for stable inter trochanteric fractures. The use of intramedullary nails e.g. PFN
      is beneficial in treating inter trochanteric fractures with comminution and loss
      of lateral buttress. Intramedullary implants have been proven to have increased
      success rates in subtrochanteric fractures and should be preferred over
      extramedullary plate fixation systems.

PMID- 25983452
TI  - Biomechanical investigation into the torsional failure of immature long bone.
AB  - Approximately 50% of infant and toddler long bone fractures are attributed to non
      accidental trauma; however, differentiating from benign mechanisms is subjective,
      due to an absence of evidence-based diagnostic tools. Previous studies
      investigated small ranges of rotational velocities in animal long bone models,
      although did not report the variation in the spiral fracture angle. This study
      considered the fracture angle as a potential clinical measure, correlating this
      data with a wider range of rotational velocities. The spiral fracture angle was
      measured relative to the long axis, whilst noting the narrowest diaphysial
      diameter, location of the fracture, and the extent of comminution and periosteal
      disruption. Twenty-six bones failed in spiral fracture, with the potting material
      failing in the remaining tests. All spiral fractures centred on the narrowest
      diaphysial diameter. Slower rotational velocities caused fracture angles
      approaching 45 degrees , whereas fractures at greater velocities caused fracture
      angles nearer 30 degrees . A relatively strong trend (R (2) = 0.78) is reported
      when the normalised fracture angle (against the narrowest diaphysial dimension)
      was plotted against the rotational rate. A relationship has been identified
      between the angle of spiral fracture and the rotational velocity using the
      immature bovine metatarsal model. This trend forms a scientific foundation from
      which to explore developing a diagnostic, evidence-based tool that may ultimately
      serve to assist differentiating between accidental and non-accidental injury. 

PMID- 25983453
TI  - Comparative prospective study of proximal femoral nail and dynamic hip screw in
      treatment of intertrochanteric fracture femur.
AB  - OBJECTIVES: The aim of this study was to compare the outcome of intertrochanteric
      fractures treated with Dynamic Hip Screw and Proximal Femoral nail. METHODS: This
      study was conducted on 50 cases of Intertrochanteric fractures of femur treated
      by a dynamic hip screw and proximal femoral nail. Patients were operated on
      standard fracture table under image intensifier control. RESULTS: The average age
      of the patient was 62.3 years. Most common mechanism of fracture was domestic
      fall. Twenty percent four percent had stable, 58% unstable and 18% reverse
      oblique pattern of fracture. The unstable pattern was more common in old aged
      patients with higher grade of osteoporosis. The average blood loss was 100 and
      250 ml in PFN and DHS group respectively. In PFN there were more no. of radiation
      exposure intraoperatively. The average operating time for the patients treated
      with PFN was 55 min as compared to 87 min in patients treated with DHS. Total
      complications were 15% with implant failure 6%, infection 4%, nonunion 2% and
      greater trochanter splintering 4%. In the PFN group the amount of sliding on X
      rays was less as compared to DHS. The patients treated with PFN started early
      ambulation as they had better Harris Hip Score in the early period (at 1 and 3
      month). In the long term both the implant had almost similar functional outcomes.
      CONCLUSION: The DHS was tolerated better by young patients with stable fracture
      while PFN had a better outcome with osteoporotic patients and weak bone mass and
      reverse oblique fractures.

PMID- 25983454
TI  - Humeral shaft fracture management, a prospective study; nailing or plating.
AB  - INTRODUCTION: In this fast moving & advancing era no body want to remain
      handicapped in immobilization by cast with limited movement. As our knowledge is
      growing, orthopedic implants and appliances also advancing, and creating a very
      potential options to manage fracture shaft of humerus by internal fixation either
      by plate osteosynthesis or interlocking nailing. We are here to evaluate the
      options of internal fixation; nailing and plating. MATERIAL AND METHOD: We
      prospectively evaluated the results of 30 patients having humeral Shaft fracture.
      Who were internally fixed by antegrade interlocking nailing (15) and DCP plate
      (15). Patients are followed up on average of 16-19 months and results were
      evaluated with standard protocol. RESULTS: All fractures united uneventfully with
      usual complication. However we need 2 reoperation in nailing and 1 case of
      plating for bone grafting. CONCLUSION: Internal fixation have immense use in
      providing better results in form of less deformity, early mobilization and good
      union. Plating is better option for fixation in terms of less union time, better
      joint function and lesser reoperation However Nailing is good alternative as
      minimal invasive approach, less infection, less nerve injury, less chance of
      implant failure.

PMID- 25983455
TI  - Study of patient satisfaction in a surgical unit of a tertiary care teaching
      hospital.
AB  - BACKGROUND: The hospitals have evolved from being an isolated sanatorium to a
      place with five star facilities. Patients and their relatives coming to the
      hospital not only expect world-class treatment, but also other facilities to make
      their stay comfortable in the hospital. This change in expectation has come due
      to tremendous growth of media and its exposure, as well as commercialization and
      improvement in facilities. The aim of this study was to evaluate the level of
      patient/relatives satisfaction at tertiary care teaching hospital and feedback
      from them for improvement of the same. METHODS: The study was conducted by 1.
      Review of available national and international literature on the subject. 2.
      Carrying out survey amongst 50 patients and their relatives at one of the
      surgical unit by using structured questionnaire. 3. By analyzing the data using
      appropriate statistical methods. RESULTS: Eighty two percent people were
      satisfied with the service at admission counter while 81% were satisfied with
      room preparation at the time of admission. The nursing services satisfied 80% of
      people while 92% were satisfied with explanation about disease and treatment by
      doctor. The behavior of nurses, doctors and orderlies satisfied 92, 92 and 83% of
      people. The cleanliness of toilets satisfied only 49% while diet services
      satisfied 78% of people. CONCLUSION: The five major satisfiers were behavior of
      doctors, explanation about disease and treatment, courtesy of staff at admission
      counter, behavior and cooperation of nurses. The five major dissatisfiers were
      cleanliness of toilets, quality of food, explanation about rules and regulation,
      behavior of orderlies and sanitary attendant and room preparedness.

PMID- 25983456
TI  - Intrapelvic migration of hip lag screw of proximal femoral nail-sequele to a
      paradoxical reverse Z effect and their critical analysis.
AB  - A 40-year-male treated with hip screw for unstable inter trochanteric fracture
      femur, had an implant failure after an aggressive therapy session .The Dynamic
      Condylar Screw was removed and fracture was fixed with Proximal Femoral Nail. The
      nail also failed to achieve its goal of fracture union, as a result of a unique
      type of reverse Z effect, in contradiction to expected Z effect resulting in
      intrapelvic migration of proximal hip lag screw of the proximal femoral nail. 

PMID- 25983457
TI  - Os intermetatarseum - A case report.
AB  - Accessory ossicles and sesamoid bones are skeletal variations, more commonly seen
      in the region of foot and ankle. Most such accessory and sesamoid bones remain
      asymptomatic. However overuse and trauma can make such feet symptomatic.
      Knowledge of such bony ossicles is essential in the management of patients
      presenting with foot pain. Dorsal foot pain can be caused by a symptomatic Os
      intermetatarseum - an accessory ossicle found between the bases of first and
      second metatarsals and the medial cuneiform. Its incidence has not been well
      established because of insufficient appropriate multi-centric anatomical,
      radiological and orthopaedic studies. A case of dorsal foot pain in a soccer
      player, caused by an Os intermetatarseum is reported here. A brief review of the
      literature is also presented. 

PMID- 25983458
TI  - Salvage of proximal tibia fracture treated with locked compression plate.
AB  - The treatment of displaced proximal tibial fractures is challenging. Recent
      developments in the techniques of internal fixation, including the development of
      locking plates and minimally invasive surgical techniques have revolutionaries
      the treatment of such fractures. We present a case of proximal displaced tibial
      fracture that was treated with anatomical proximal tibial locking plate using
      minimally invasive percutaneous plate osteosynthesis. Patient made uneventful
      recovery even after he sustained re-injury and plate bending and was manipulated
      under anaesthesia for the same. 

PMID- 25983459
TI  - Chronic osteomyelitis of ilium presenting as an expansile mutiloculated lytic
      lesion - A case report.
AB  - Chronic iliac osteomyelitis classically presents radiologically as an ill defined
      radiolucent lesion with moth eaten appearance along with periosteal reaction and
      sequestrum formation. Our case report presents a rare radiological picture of
      iliac bone osteomyelitis in the form of an expansile mutiloculated lytic lesion. 

PMID- 25983460
TI  - Management of osteonecrosis of proximal tibia using trabecular osteonecrotic
      rods.
AB  - Osteonecrosis of the knee is a well-described cause of acute knee pain. It can
      lead to significant functional impairment, rapid arthritic joint changes and
      subsequent collapse. Several hypotheses exist different treatment options are
      used ranging from conservative management to joint arthroplasty. The majority of
      cases involve the distal femoral condyle and to a much lesser extent the medial
      tibial plateau. We are presenting a rare case of osteonecrosis of the proximal
      tibia affecting the lateral tibial condyle in 44 years old Caucasian male which
      was treated successfully using osteonecrotic tantalum rods with 26 month follow
      up. 

PMID- 25983461
TI  - Estimation of radiographic measurements in fracture distal radius. Should we be
      using digital measuring tools?

PMID- 25983462
TI  - Outcome of arthroscopic drainage and debridement with continuous suction
      irrigation technique in acute septic arthritis.
AB  - PURPOSE: The purpose of this study was to determine the clinical course and
      functional outcome of acute septic arthritis treated by arthroscopic drainage and
      debridement with continuous suction irrigation. METHODS: Eighteen subsequent
      cases of acute septic arthritis of hip and knee were included in this study.
      Complete hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP), blood sugar, liver and kidney function test was done. Plain radiographs
      and ultrasound of affected joints were done. Joint aspirate was analyzed for gram
      staining, AFB staining, culture/sensitivity, biochemistry and cytology.
      Quantitative CRP was repeated every third day till normal CRP level was noted.
      Intravenous cloxacillin 25-50 mg/kg was started according to WHO protocol and was
      later changed to specific antibiotics after culture reports. Arthroscopic
      drainage and debridement of joints was done through standard portals and two
      tubes were placed in each joint for continuous suction and irrigation. Continuous
      suction irrigation was used till the effluent saline from the joint was clear.
      Functional outcome was documented as per Harris hip score for hips and Lysholm
      score for knee joint. Scoring was done before surgery, at one month and at three
      months. The duration of intravenous antibiotics and hospitalization was recorded.
      RESULTS: Out of eighteen cases 83.33% were males and 14.67% females. The mean age
      was 22 years (+/-12.01). The mean duration of symptoms was 4.33 days (+/-1.41).
      According to Gachter classification 88.88% of cases were stage 2 infection and
      11.12% cases in stage 1 at the time of arthroscopy. The mean duration of hospital
      stay was 14.61 days (+/-4.01). Intravenous antibiotics were given for a mean
      period of 9.33 days (+/-2.16). The mean pre-operative Harris score was 13.6 (+/
      2.07) which improved to 98 (+/-1.87) at 3 months and all the cases had painless
      normal range of movements. Mean pre-operative Lysholm score was 38.38 (+/-4.29)
      and it improved to 98.84 (+/-2.19) at 3 months. There were no sequelae of septic
      arthritis in any case. CONCLUSION: Early arthroscopic decompression and
      debridement of septic arthritis with continuous suction irrigation can eradicate
      the infection. The duration of intravenous antibiotics and the hospital stay
      required is shorter. The functional outcome of joints is satisfactory.

PMID- 25983463
TI  - Expanding the utility of modified vascularized femoral periosteal bone-flaps: An
      analysis of its form and a comparison with a conventional-bone-graft.
AB  - BACKGROUND: Vascularized medial femoral condyle (MFC) corticoperiosteal bone-flap
      is a well-accepted technique when dealing with tissue defects or infection. Its
      role in refractory conditions and in the possible use for options concerning
      modifications of this bone-flap compared to a conventional iliac bone graft
      (conventional-graft) are rarely discussed. METHODS: We reviewed 21 consecutive
      cases concerning alternatives with some modifications of original MFC bone-flap
      surgery used to treat refractory conditions with bone defects, necrosis, or
      infection in the extremities. We present our devised approaches for this
      boneflap, and especially modifications of the grafted bone (including strut bone,
      perforator to the vastus medialis muscle, and the use of one vascular pedicle for
      some bone flaps) as well as the combined use of artificial bone as hybrid bone
      transplantation. We also compared the clinical results of 21 cases that received
      a conventional-graft. RESULTS AND CONCLUSIONS: Following flap placement, 100% of
      the nonunion sites healed in an average of 2 months, which was significantly
      shorter than 5.5 months for the conventional-graft. The results showed the
      expanding possibility for options with regard to the form and options of this
      bone-flap as well as the shortening the duration of treatment, especially at the
      site of an infected distal tibia, insertion of the Achilles tendon on the
      posterior aspect of calcaneal osteomyelitis, distal end of the clavicle, clavicle
      or forearm with a bone defect, small bones with refractory conditions, and a
      femur without implant failure. However, it was not efficient for treating a
      forearm without bone defect.

PMID- 25983464
TI  - Is the femoral head dead or alive before surgery of slipped capital femoral
      epiphysis? Interest of perfusion Magnetic Resonance Imaging.
AB  - BACKGROUND: The most common complication of slipped capital femoral epiphysis
      (SCFE) is avascular necrosis (AVN) of the femoral head. Surgical treatments
      including reduction of the femoral head are considered as a risk factor for
      avascular necrosis. The purpose of this study was to investigate the role of
      perfusion Magnetic Resonance Imaging (MRI) into the surgical decision-making
      sequence. METHODS: Eighteen children with 19 slipped capital femoral epiphysis
      were retrospectively included. SFCE was unstable in nine cases and stable in ten
      cases. The slip angle was higher than 60 degrees  in 14 cases. Perfusion MRI with
      dynamic gadolinium-enhanced subtraction sequences were done in all the cases
      before and after surgical treatment. RESULTS: On nineteen hips, eight were
      devascularized before surgery. All were unstable. After surgery, six on eight had
      a complete revascularization, one had a focal necrosis and one remained
      devascularized. A postoperative devascularization with normal preoperative MRI
      was noted once. On nineteen hips, a total of three avascular necrosis occurred.
      CONCLUSION: Perfusion MRI is useful to assess preoperative and postoperative
      vascular status in SFCE. Preoperative devascularization could improve or stay
      equal after surgical treatment. Persistent devascularization could be responsible
      for avascular necrosis of the femoral head.

PMID- 25983465
TI  - Pachydermoperiostosis - a case report of complete form and literature review.
AB  - Pachydermoperiostosis, also known as Touraine-Solente-Gole syndrome/Rosenfeld
      Kloepfer syndrome/primary or idiopathic Hypertrophic osteoarthropathy, is an
      autosomal-dominant/autosomal recessive inherited disorder with variable
      expression. In its complete form, it is characterized by pachyderma (thickening
      of the facial skin), skeletal changes (periostosis), excessive sweating
      (hyperhydrosis), and acropachia (digital clubbing). We report a patient with
      skeletal symptoms, associated with pachyderma and clubbing of fingers.
      Radiographs of patient showed periosteosis of distal end of long bones. We review
      the characteristic features of this syndrome. The patient required a close follow
      up because of complications that might develop on the long-term. 

PMID- 25983466
TI  - Neurilemmoma of median nerve.
AB  - Neurilemmomas constitute one of the most common tumors of peripheral nerves.
      Rarer amongst them is their occurrence in median nerve in the region of arm. A
      sixteen-year-old female presented with painless mass in right arm which was non
      tender on palpation with positive Tinel's sign and no motor or sensory deficit in
      the affected arm. Ultrasound examination revealed an eccentrically arising mass
      of size 19 * 11 mm along median nerve. MRI study revealed a mass homogenously
      isointense on T1 weighted images and hyperintense in T2 weighted images placed
      eccentrically in relation to median nerve in arm. Excisional biopsy under loupe
      magnification was carried out which revealed the mass to be neurilemmoma. This
      slowly growing benign tumor of peripheral nerves with an incidence of 5% with 14%
      involvement of Median nerve can be enucleated from the nerve with little or no
      damage. In spite of advanced imaging studies the mass cannot be differentiated
      preoperatively from another peripheral nerve sheath tumor neurofibroma. Both
      these tumors although bearing some clinical and imaging resemblance carry
      different intraoperative findings, histopathological features and post-operative
      results. 

PMID- 25983467
TI  - Bicondylar Hoffa's fracture with patellar dislocation - a rare case.
AB  - Bicondylar Hoffa's fractures of the femur is very uncommon. Conjoint bicondylar
      Hoffa fracture with ipsilateral patellar dislocation, Bicondylar Hoffa's with
      patellar fracture and extensor mechanism rupture has been described in
      literature. We report a case of unconjoint bicondylar Hoffa's fracture with
      lateral patellar dislocation in 17-year-old male patient treated with open
      reduction and cancellous screw fixation that subsequently healed well with good
      functional outcome. 

PMID- 25983468
TI  - Anterior dislocation of hip following DHS fixation of intertrochanteric fracture:
      A case report.
AB  - Intertrochanteric fractures are commonly seen in elderly population. 90% of these
      occur following a trivial fall. Dynamic hip screw fixation is one of the most
      common modality of treatment, although intramedullary fixation devices are
      gaining popularity in recent times, especially in unstable fractures. Dislocation
      of hip following a DHS fixation of hip is a very rare complication. There are
      only two case reports which describes dislocation of hip following DHS fixation
      of an intertrochanteric fracture. Here we present a case of anterior dislocation
      of hip following DHS fixation of an intertrochanteric fracture. We also discuss
      about the possible causes of this rare complication, its management and follow
      up. 

PMID- 25983470
TI  - The term 'diaphyseal achalasia' must be changed with the term 'diaphyseal
      aclasis'.

PMID- 25983469
TI  - Closed retrograde multiple intramedullary Kirschner wires fixation for humeral
      shaft fractures with the limb flexed over an articulated support.
AB  - OBJECTIVE: To evaluate the results of multiple closed intramedullary Kirschner
      wiring via a supracondylar entry point for humeral shaft fractures. PATIENTS AND
      METHODS: The charts of 37 patients with humeral shaft fractures treated with the
      Hackethal's technique between January 2007 and December 2011 were reviewed
      retrospectively. The operation was performed with the patient lying in supine (n
      = 22) or lateral (n = 15) position. The elbow was flexed over an articulated
      support with the arm kept in a vertical position. Thirty-three patients were
      available for final evaluation with a mean follow-up delay of 14 (range, 6-24)
      months. We were concerned about fracture union, range of motion of the shoulder
      and the elbow, and complications. Final evaluation used the criteria by Qidwai.
      RESULTS: Bone union rate was 94%. Restriction of ranges of motion of the shoulder
      more than 20 degrees  was noticed in two patients due to protruding wires. Three
      patients developed limitation of elbow extension owing to backing out of the
      wires. The overall results were excellent (n = 26; 79%), good (n = 4; 12%), and
      poor (n = 3; 9%). CONCLUSION: Closed Hackethal's technique using K-wires gives
      satisfactory results in terms of bone union and elbow and shoulder function in
      selected humeral shaft fractures. The articulated support precludes the
      transolecranon traction.

PMID- 25983471
TI  - Quiz - 2014.

PMID- 25983472
TI  - Dorsal wrist ganglion: Current review of literature.
AB  - Ganglion cyst is the most common soft tissue tumour of hand. Sixty to seventy
      percent of ganglion cysts are found in the dorsal aspect of the wrist. They may
      affect any age group; however they are more common in the twenties to forties.
      Its origin and pathogenesis remains enigmatic. Non-surgical treatment is
      unreliable with a high recurrence rates. Open surgical excision leads to
      unsightly scar and poor outcome. Arthroscopy excision has shown very promising
      result with very low recurrence rate. We reviewed the current literature
      available on dorsal wrist ganglion. 

PMID- 25983473
TI  - Fracture of distal end clavicle: A review.
AB  - Management of fracture distal end clavicle has always puzzled the orthopaedic
      surgeons. Now-a-days with a relatively active lifestyle, patients want better
      results both cosmetically and functionally. Despite so much literature available
      for the management of this common fracture, there is no consensus regarding the
      gold standard treatment for this fracture. In this article, we reviewed the
      literature on various techniques of management for this fracture, both
      conservative as well as surgical, and their merits and demerits. 

PMID- 25983474
TI  - Comparison of treatment of unstable intra articular fractures of distal radius
      with locking plate versus non-locking plate fixation.
AB  - INTRODUCTION: Unstable intra articular fractures of distal radius are frequently
      being managed with open reduction and internal fixation. Of late in some
      biomechanical studies locking plates have been shown to be better in terms of
      maintenance of radiological parameters in comparison to non-locking plates. We
      conducted this study to know whether this biomechanical superiority of locking
      plates is converted in to better clinical outcomes. MATERIALS AND METHODS: A
      study was conducted in 60 patients (30 in each group) with unstable intra
      articular fractures of distal radius who were treated by open reduction and
      internal fixation with locking plates and non-locking plates. Patients were
      evaluated for radiological parameters (intra articular step off, radial height,
      radial tilt, volar tilt) and functional parameters (flexion, extension, radial
      deviation, ulnar deviation, pronation, supination grip strength) at two year
      follow up. Overall outcome was evaluated by scoring systems of Gartland and
      Werley and modified Green O' Brien. RESULTS: The change in radiological
      parameters from immediate post op to latest at two year in locking plate group
      was not significant for radial height, radial tilt, volar tilt, but ulnar
      variance whereas in non-locking plate there was significant change in radial
      height, volar tilt, ulnar variance but no significant change in radial
      inclination. In clinical and functional outcome no significant difference was
      found at two year follow up. CONCLUSIONS: Locking plates maintain the
      radiological parameters better than non-locking plates but functional outcome are
      same for both plates at two year after surgery.

PMID- 25983475
TI  - Functional anthropometric measurements of Indian pelvis.
AB  - PURPOSE: To determine the normal values of several radiographic measurements of
      hip and pelvis in individuals of Indian population. MATERIAL AND METHODS: We
      conducted a cross-sectional study of Indian population and calculated mean and
      variation seen in different parameters in Indian pelvis. We took the plain X-ray
      of randomly selected hundred patients in identical position with 20%
      magnification factor. Different parameters including acetabular inclination
      angle, cup size, tear drop position, neck shaft angle, neck offset, abductor
      lever arm and head size were drawn on the X-rays and values measured. RESULTS:
      100 subjects were taken (63 male and 37 female). The mean of acetabular
      inclination angle was 37.70 +/- 3.82 degrees  (30-47 degrees ). The mean neck
      shaft angle was131.53 +/- 7.70 degrees  (114-158) the most commonly occurring
      value was 131 degrees . The mean abductor lever arm was 38.48 mm +/- 5.77 (23-54)
      with the mode of 40. The mean cup size was 48.9 +/- 3.67 mm (34-58) with the most
      commonly occurring value as 50. The mean angle from tip of trochanter to center
      of head was 80.2 +/- 9.1 (62-110). Among all the seven parameters correlations
      were drawn. There were in all 22 correlations out of which 14 were statistically
      significant. CONCLUSION: Since there is significant difference between the neck
      shaft angles and other measurements of Indian population than to the European
      population, an evaluation in the design of the implant by the Indian
      manufacturers is recommended. Also this study proposes that the normal values of
      our own population be used as reference values in interpreting standard
      radiographs of pelvis with both hips.

PMID- 25983476
TI  - Functional evaluation of patient after arthroscopic repair of rotator cuff tear.
AB  - BACKGROUND: Rotator cuff tear is a common problem either after trauma or after
      degenerative tear in old age group. Arthroscopic repair is the current concept of
      rotator cuff repair. Here, we are trying to evaluate the functional outcome after
      arthroscopic repair of full thickness rotator cuff tear (single row) in Indian
      population. MATERIALS AND METHODS: Twenty five patients (14 males and 11 females)
      who underwent arthroscopic repair of full thickness rotator cuff tear at a single
      institution were included in the study. Postoperatively patient's shoulder was
      rated according to UCLA score, pain was graded according to the visual analog
      score. The range of motion was analysed and documented. RESULTS: The mean age of
      the patients were 50.48 years. The preoperative VAS score mode was 7 and post
      operative VAS was 1 (p value <0.001). The UCLA grading was good in 80% (n = 20),
      fair in 12% (n = 3), excellent in 8% (n = 2) and poor results were seen in none
      of the patients. The mean UCLA improved from a score of 15.84 to 30.28 with a p
      value <0.001. Mean postoperative forward flexion was 161.6 degrees , mean
      abduction was 147.6 degrees  and mean external rotation was 45.4 degrees .
      CONCLUSION: Arthroscopic repair is a good procedure for full thickness rotator
      cuff tear with minimal complications. The newer double row repair claims to be
      biomechanically superior with faster healing rates without functional advantages,
      hence we used a single row repair considering the Indian population and the cost
      effectiveness of the surgery with good to excellent results.

PMID- 25983477
TI  - Canine tooth in hand - A rare entity.
AB  - The hand plays an important role in day to day activities and is more prone for
      accidental injuries. Injuries to the hand are frequently associated with foreign
      body penetration. Many a times the foreign body is not detected at the initial
      visit and can later present with other complications. We present a case of canine
      tooth presenting as a retained foreign body in the hand following a dog bite. The
      article stresses the importance of looking for foreign bodies in penetrating hand
      injuries, even in wounds that seem to be minor in nature. 

PMID- 25983478
TI  - Post-traumatic dynamic hallux varus instability.
AB  - Acquired hallux varus secondary to traumatic disruption of the lateral joint
      structures of the 1st MTPJ is uncommon and has only been reported in the
      literature once previously.(4) We present a case of traumatic hallux varus that
      is unique since the deformity is dynamic in nature. In our patient the hallux
      remained reduced on standing weight bearing films, and luxated only during
      fluoroscopic stress testing. We also describe our surgical correction where a
      soft tissue anchor alone was utilized to stabilize the joint through repair of
      the lateral capsule and collateral ligament. One year following the described
      repair the patient reports no limitations in performing activities of daily
      living, and complains of only mild pain with recreational activities. 

PMID- 25983480
TI  - Unusual ankle fracture: A case report and literature review.
AB  - Fractures of the talus are uncommon, and talar body fractures in the sagittal
      plane are still rarer. The aim of its treatment is urgent anatomic reduction to
      restore congruency of the ankle and to reduce the risk of avascular necrosis by
      preserving any remaining blood supply. We report the case of a body talar
      fracture in sagittal plane associated with fracture of the medial malleolus in a
      young adult; the mechanism of the fracture was plantar hyperflexion, internal
      rotation and axial compression. We perform an open reduction and stabilization
      with two screws for the talus and screw the medial malleolus. At 14 months
      following the injury patient had good range of movement with little pain. The
      mechanism is discussed along with a literature review. 

PMID- 25983479
TI  - Management of recurrent multiple osteochondral lesions of the talus (OCLT) in a
      young active patient.
AB  - Management of recurrent osteochondral lesion of talus in a young active male is a
      challenging problem. We present one such case of recurrent talar osteochondral
      lesions treated by Autologous Matrix Induced Chondrogenesis (AMIC). Patient had a
      good functional outcome at short-term follow up. We also describe the technique
      and review the literature regarding this novel technique. 

PMID- 25983481
TI  - Simultaneous double interphalangeal joints dislocation in a finger in a teenager.
AB  - BACKGROUND: Simultaneous dislocation of the proximal and distal interphalangeal
      joints of the same finger is a rare event. In literature simultaneous double
      interphalangeal dislocation in the same finger has been reported only one case in
      a skeletally immature patient which was a fourteen year old male. Our case was
      twelve years old which is the youngest case in the literature that has been
      reported. CASE DESCRIPTION: A 12-year-old male injured his right ring finger
      while playing football. Examination revealed a stepladder deformity. There was no
      sign of neurovascular damage. Radiographs showed dorsal dislocation of both the
      proximal and distal interphalangeal joints. Reduction of the double dislocation
      was easily achieved by simple longitudinal traction. The finger was splinted in
      the intrinsic plus position for 3 weeks and active range of motion was then
      allowed. LITERATURE REVIEW: The most prevalent cause of injury was a sport
      accident. The left hand was less often involved than the right hand. The finger
      most often injured was the little finger followed by the ring finger, middle
      finger and the index finger. Closed reduction is the treatment of choice if there
      is no soft tissue interposition that prohibits the procedure. In most cases,
      longitudinal traction was sufficient for closed reduction. CLINICAL RELEVANCE: We
      report the second case of simultaneous proximal interphalangeal (PIP) and distal
      interphalangeal (DIP) joints dislocations in one finger in a 12-year-old non
      athletic boy; which is the youngest case in the literature, managed by closed
      reduction and early mobilization, with excellent outcome.

PMID- 25983482
TI  - Vascular leiomyoma of an extremity: Report of two cases with MRI and
      histopathologic correlation.
AB  - Vascular leiomyoma is a benign, usually solitary tumor arising from the tunica
      media of the vein. It can occur anywhere in the body wherever smooth muscle is
      present. These masses are commonly found in the uterus, urogenital tract and
      gastrointestinal tract but also less commonly in the extremities. They occur more
      often in the lower extremities than the upper extremities. Females are more
      affected than males and are generally seen in the third and fourth decades of
      life. We present magnetic resonance imaging, and histopathologic features of two
      pathology proven subcutaneous vascular leiomyomas of the hand and lower leg. 

PMID- 25983483
TI  - Use of Keratome 1-0 for percutaneous Tendo Achilles tenotomy for correction of
      equinus deformity in club foot.

PMID- 25983484
TI  - Quiz.

PMID- 25983485
TI  - Comparison of treatment of fracture midshaft clavicle in adults by external
      fixator with conservative treatment.
AB  - PURPOSE: High rate of malunion and non union in displaced fracture clavicle
      treated conservatively lead to use of different types of internal fixation
      methods which also were found to be associated with various complications.
      Moreover their superiority over conservative treatment has not been established.
      This study was designed to compare clinical outcome of conservative treatment
      with external fixator in cases with displaced midshaft clavicle fractures.
      METHODS: Fifty adult consenting cases of acute midshaft fracture clavicle,
      displaced >15 mm were included. Twenty five cases were allotted to conservative
      (group A) and external fixator (group B) each. In group A treatment was given in
      form of clavicle brace. In group B schanz pins were inserted obliquely between
      supero-inferior and anterior-posterior direction and connected with rod. The
      outcome was measured by Constant score, union time and complications. RESULTS:
      Mean radiographic union time in group A was 23.45 +/- 1.40 weeks (with 8% non
      union and 80% malunion) and in group B it was 9.36 +/- 1.49 weeks. Mean Constant
      score at 6 months in group A was 78.28 +/- 6.45 and in group B 92.72 +/- 1.48.
      Mean shortening at 6 months in group A was 19.36 mm. In group B shortening at 6
      months was noticed in three cases (6, 5, 6 mm). CONCLUSION: Close reduction of
      acute fracture mid clavicle and application of external fixator is a simple
      procedure providing the benefits of rigid fixation and undisturbed fracture
      environment. Pain relief is faster, union time is shorter and there are no
      hardware related problems.

PMID- 25983486
TI  - Management of fractures of the distal third tibia by minimally invasive plate
      osteosynthesis - A prospective series of 50 patients.
AB  - BACKGROUND: Minimally invasive plate osteosynthesis (MIPO) is an established
      technique for fixation of fractures of the distal third tibia. Our study aimed to
      manage intra articular and extraarticular fractures of the distal third tibia by
      the minimally invasive plate osteosynthesis technique and follow them
      prospectively. Clinical and radiological outcomes were studied and clinical
      indications & efficacy of the procedure reviewed. Though many studies on the
      subject have been done previously, these have been retrospective reviews or small
      series. METHODS: From May 2010 to May 2013, 50 patients of closed distal tibial
      fractures were operated by MIPO technique with a distal tibial anatomical locking
      plate having 4.5/5 proximal and 3.5/4 distal screw holes. The follow up duration
      was for 3 years. RESULTS: The mean fracture healing time was 21.4 weeks (range 16
      32 weeks) and average AOFAS score 95.06 was out of a total possible 100 points.
      At last follow up, superficial infection occurred in 5 patients (10%); deep
      infection, implant failure and malunion in 1-patient each (2%). CONCLUSION: MIPO
      technique provides good, though slightly delayed bone healing and decreases
      incidence of nonunion and need for bone grafting. This technique should be used
      in distal tibia fractures where locked nailing cannot be done like fractures with
      small distal metaphyseal fragments, vertical splits, markedly comminuted
      fractures and in fractures with intra-articular extension.

PMID- 25983487
TI  - Evaluation of proximal femoral locking plate in unstable extracapsular proximal
      femoral fractures: Surgical technique & mid term follow up results.
AB  - BACKGROUND: Stable trochanteric femur fractures can be treated successfully with
      conventional implants such as sliding hip screw, cephalomedullary nails, angular
      blade plates. However comminuted and unstable inter or subtrochanteric fractures
      with or without osteoporosis are challenging & prone to complications. The PF-LCP
      is a new implant that allows angular stability by creating fixed angle block for
      treatment of complex, comminuted proximal femoral fractures. METHOD: We reviewed
      30 patients with unstable inter or subtrochanteric fractures, which were
      stabilized with PF-LCP. Mean age of patient was 65 years, and average operative
      time was 80 min. Patients were followed up for a period of 3 years (June 2010
      June 2013). Patients were examined regularly at 3 weekly interval for signs of
      union (radiological & clinical), varus collapse (neck-shaft angle), limb
      shortening, and hardware failure. RESULT: All patients showed signs of union at
      an average of 9 weeks (8-10 weeks), with minimum varus collapse (<10 degrees ), &
      no limb shortening and hardware failure. Results were analysed using IOWA
      (Larson) hip scoring. Average IOWA hip score was 77.5. CONCLUSION: PF-LCP
      represents a feasible alternative for treatment of unstable inter- or
      subtrochanteric fractures.

PMID- 25983488
TI  - Sacroiliac tuberculosis - A neglected differential in refractory low back pain -
      Our series of 35 patients.
AB  - INTRODUCTION: Osteo-articular tuberculosis accounts for 1-3% of which 5-8%
      involves sacro-illiac joint. Isolated sacroiliac involvement is very rare. It
      usually presents as vague back pain. Plain radiographs are often inconclusive.
      Due to rarity of lesion, vague symptoms and non-conclusive X-rays the diagnosis
      is further delayed. We present a series of 35 patients presented with sacroiliac
      tuberculosis. METHODS: 35 patients were diagnosed of sacroiliac tuberculosis from
      January 2008 to December 2011. After a thorough history and clinical examination,
      patients were taken up for X-rays and MRI scans. Ultrasound guided needle
      aspiration was done from suspected area. After histological confirmation of the
      diagnosis, patients were treated with anti tubercular therapy. RESULTS:
      Persistent low back pain and difficulty with walking were noted in all patients.
      There were 21 males (60%) and 14 females and the age ranged from 22 to 55 years
      (mean: 27 years). Most of the patients (91.4%) had unilateral disease (32
      patients). Results of conservative management were good. 21 (60%) of our patients
      achieved bony ankylosis at the end of study. 9 patients did not respond to
      conservative management where surgical debridement was done. 4 of these cases had
      MDR tuberculosis. CONCLUSION: Sacroiliac tuberculosis must be kept as a
      differential in all refractory low back pain particularly in endemic areas. MRI
      is very helpful in early diagnosis of disease. In the early stages of the
      infection aspiration using a closed needle biopsy is recommended. An open biopsy
      is essential when the aspirate yields no growth. Open debridement should be done
      in those not responding to conservative management.

PMID- 25983489
TI  - Traumatic bilateral posterior hip dislocation in 10 year old male child.
AB  - Traumatic bilateral posterior hip dislocation in skeletally immature patient is
      reported very less in literature. We report a 10 yr old boy presented to us
      following farmyard injury with bilateral posterior hip dislocation, which was
      reduced manually under sedation with uneventful follow-up and complete hip range
      of motion at 2 year. 

PMID- 25983490
TI  - Disseminated synovial chondromatosis of the knee treated by open radical
      synovectomy using combined anterior and posterior approaches.
AB  - Synovial chondromatosis of the knee is a rare benign neoplasm of the synovium.
      Likewise, uncertainty on management still prevails. Though rare, it nevertheless
      warrants greater emphasis than it receives in the literature to allow correct
      diagnosis and accurate early surgical intervention. It predominantly involves the
      anterior compartment of the knee and disseminated disease is extremely rare. The
      optimal approach for surgical treatment of such an extensive synovial
      chondromatosis of knee remains unclear. Herein, we describe a case of extensive
      generalized synovial chondromatosis of the knee extending into the Baker's cyst
      in a 30 years old female. A diagnosis of synovial chondromatosis was made by
      clinical evaluation and MR imaging and confirmed by histopathological
      examination. Patient was successfully treated by open radical synovectomy of knee
      using both anterior and posterior approaches in a single step procedure. 

PMID- 25983491
TI  - Morel-Lavallee lesion in distal thigh: A case report.
AB  - It is a relatively rare condition involving a close degloving injury due to
      direct trauma with tangential force followed by the separation of the
      subcutaneous tissue from the underlying fascia. The rupture of small perforating
      vessels in this area, resulting in the formation of a cavity that filled with
      blood, lymph and fat foci, the latter being sometimes necrotic. Morel-Lavallee
      lesion was originally described in the lateral aspect of the proximal thigh,
      which is the most common site of this lesion; however other anatomic sites such
      as periscapular, lumbar and gluteal regions, ankles and knees have been described
      in the literature. Various methods of treatment has been described, but open
      debridement can result in a successful functional outcome. 

PMID- 25983492
TI  - An isolated middle cuneiform dislocation with a rare violence. Case report and
      literature review.
AB  - OBJECTIVE: To report how a case of isolated middle cuneiform dislocation is
      diagnosed mainly by suspicion and careful imaging. CLINICAL PRESENTATION AND
      INTERVENTION: A 39-year-old male presented with localized foot pain after a
      sideways compression of the foot on ground. X-rays revealed an empty middle
      cuneiform site .CT confirmed the finding of an isolated middle cuneiform
      dislocation .He had operative reduction and stabilization, followed by a good
      foot function. CONCLUSION: The diagnosis of such an injury should be kept in mind
      in patients while examining the foot injuries in general. Imaging including CT
      scan of the foot is necessary to confirm the diagnosis and to plan for the
      surgical treatment. The case was presented to highlight the need to watch out for
      them and care for them at the earliest.

PMID- 25983493
TI  - Nonoperative treatment of closed total talus dislocation without fracture: A case
      report and literature review.
AB  - Complete dislocation of the talus not accompanied by a fracture is a very rare
      injury. Most cases reported are open talus dislocations; closed dislocations are
      rarely seen. The functional prognosis is poor due to osteonecrosis of the talus
      which develops in the majority of cases. We present a case of lateral dislocation
      of the left talus in a 29-year-old road accident victim, but no fracture could be
      detected in the talus and any of malleolus. Reduction of dislocation had been
      performed in emergency by external manipulation. At 1-year follow-up, the right
      ankle was pain free and stable. Motion was satisfactory: 15 degrees  dorsal
      flexion, 30 degrees  plantar flexion; the talus didn't show subluxation and
      avascular necrosis could not be detected. 

PMID- 25983494
TI  - Delayed debridement of an open total talar dislocation reimplanted in the
      emergency room.
AB  - Open total talar dislocation is a rare but well known injury. Its management is
      controversial and fraught with complications such as infection, avascular
      necrosis, and post-traumatic osteoarthritis. We report the case of a woman
      sustaining a pure open talar dislocation reduced in the emergency room.
      Debridement was done three days after the injury in the operating room. There was
      no infection. One year after surgery she complained of occasional pain.
      Ambulation was normal. She wore regular shoes. The overall alignment of the
      ankle, hindfoot, and midfoot was normal. Movements of the tibiotalar and subtalar
      joints were not impaired. She has resumed her regular activities. Radiographs
      showed no signs of avascular necrosis. All components of the treatment strategy
      of open total dislocation should be carried out in emergency. This results in
      environment close to the original biological state. Good results can be achieved
      if infection is avoided. 

PMID- 25983495
TI  - Quiz.

PMID- 25983496
TI  - Primary repair of capsuloligamentous structures of trapeziometacarpal joint: A
      preliminary study.
AB  - BACKGROUND: Isolated trapezio-metacarpal joint dislocation is uncommon and
      challenging since controversy still exists regarding its management. DESCRIPTION:
      We present a short case series in which direct repair of trapezio-metacarpal
      ligaments was done in three patients who had isolated, unstable dislocation of
      the thumb carpometacarpal joint. All of them were engaged in tasks where no
      compromise in hand functions and grip strength was affordable. The dislocation
      was addressed primarily by repair of volar oblique and dorsoradial ligaments with
      suture anchors. The joint was immobilised in a cast for 4 weeks followed by
      gradual mobilisation. RESULTS: At an average follow up of 15 months, all the
      three patients have no restriction in the range of motion. There are no symptoms
      and signs of instability. In two patients, there is no pain at all; while one
      patient has occasional pain which is mild and does not interfere with the hand
      function. Radiographic examination showed normal joint alignment and no signs of
      subluxation or early osteoarthritis. CONCLUSION: Repair of the capsuloligamentous
      complex with suture anchors may be considered as a treatment option in unstable
      trapezio-metacarpal joint dislocations in high demand patients.

PMID- 25983497
TI  - Presentation of frozen shoulder among diabetic and non-diabetic patients.
AB  - OBJECTIVE: The literature is inconsistent regarding the level of pain and
      disability in frozen shoulder patients with or without diabetes mellitus. The aim
      of this study is to evaluate some demographic features of frozen shoulder
      patients and to look into the disparity of information by comparing the level of
      pain and disability due to frozen shoulder between diabetic and non-diabetic
      people. DESIGN: This is a prospective comparative study. People with frozen
      shoulder attending an outpatient department were selected by consecutive
      sampling. Disability levels were assessed by the Shoulder Pain & Disability Index
      (SPADI). Means of pain and disability scores were compared using unpaired t-test.
      RESULTS: Among 140 persons with shoulder pain 99 (71.4%) had frozen shoulder.
      From the participating 40 frozen shoulder patients, 26 (65%) were males and 14
      (35%) were females. Seventeen participants (42.5%) were diabetic, two (5%) had
      impaired glucose tolerance and 21 (52.5%) patients were non-diabetic. Mean
      disability scores (SPADI) were 51 +/- 15.5 in diabetic and 57 +/- 16 in non
      diabetic persons. The differences in pain and disability level were not
      statistically significance (respectively, p = 0.24 and p = 0.13 at 95% confidence
      interval). CONCLUSIONS: No difference was found in level of pain and disability
      level between frozen shoulder patients with and without diabetes.

PMID- 25983498
TI  - A study of the prevalence of osteoporosis and hypovitaminosis D in patients with
      primary knee osteoarthritis.
AB  - INTRODUCTION: Osteoarthritis and Osteoporosis are highly prevalent disease, so is
      hypovitaminosis D. We tried to find out prevalence of osteoporosis and
      hypovitaminosis D in patients suffering from primary knee Osteoarthritis. We also
      compared the prevalence of oseotoporosis between general population and patients
      of primary osteoarthritis. METHODS: Patients suffering from primary knee OA were
      taken from Rheumatology OPD of Medical College Hospital and SSKM Hospital
      Kolkata, India. For each patient age and sex matched friend or relative of same
      locality was taken in the study as controls. Hospital staffs that come from
      different part of state was taken in the study as controls. The control
      population was the representative of general population. RESULTS: Total number of
      participants in this study was 206. Out of which there were 98 cases and 108
      controls. BMD status correlates significantly with Primary OA. Serum Vitamin D3
      status correlates significantly with Osteoarthritis. Age of the patients
      correlated significantly with both BMD Status and Knee OA but not with the
      vVitamin D level. There were significant correlation between the Serum Vitamin D3
      status and BMD of the subjects. CONCLUSION: Osteoporosis is prevalent both in
      general population and patients suffering from Knee Osteoarthritis and may
      increase the disability. The matter is complicated by the fact hypovitaminosis D
      is also prevalent in the population and positively correlated with both
      Osteoporosis and osteoarthrosis, though we cannot comment on further pathogenesis
      because of cross sectional design of the study.

PMID- 25983499
TI  - Titanium elastic nailing in pediatric femoral diaphyseal fractures in the age
      group of 5-16 years - A short term study.
AB  - BACKGROUND: Management of femoral diaphyseal fracture in the age group of 5-16
      years is controversial. The purpose of this study is to demonstrate the
      effectiveness of intramedullary fixation of femoral shaft fractures by using
      titanium elastic nailing system (TENS). MATERIALS AND METHODS: Between April 2011
      and April 2014, 40 pediatric patients (31 boys, 9 girls) aged 5-16 years with
      diaphyseal femoral fractures were treated by retrograde TENS fixation. Fractures
      were classified according to system of Winquest and Hansen as Grade-I (n = 18),
      Grade-II (n = 10), Grade-III (n = 7) and compound fractures according to the
      Gustilo and Anderson's classification Grade-I (n = 3), Grade-II (n = 2). The
      final results were evaluated by using Flynn's criteria. RESULTS: The mean
      duration of follow-up was 21 months (range 3-39 months). All fractures were
      radiologically united with grade 3 callus formation at 8-10 weeks period (mean 9
      weeks) and full weight bearing was possible in a mean time of 9.5 weeks.
      According to Flynn's criteria, excellent result was found in 33 patients (82.5%)
      and satisfactory in 7 patients (17.5%). Limb lengthening was noticed in 6 cases,
      varus mal-alignment was in 4 cases and rotational mal-alignment was seen in 3
      cases. Peri-operative difficulties encountered were failure of closed reduction
      in 4 cases and cork screwing of nails in 2 cases. CONCLUSION: TENS is a safe and
      effective method for the treatment of pediatric femoral shaft fractures, because
      it is minimally invasive, relatively easy to use and shows very good functional
      and cosmetic results.

PMID- 25983500
TI  - Patellar clunk in total knee arthroplasty using modified Sigma posterior
      stabilized femoral component.
AB  - AIM: The purpose of this study was to evaluate the efficacy of the enhanced PS
      femoral component design released in 2008 by DePuy. The patellar clunk syndrome
      has been reported in a significant number of patients following total knee
      arthroplasty. Design modifications of the implant have been made to reduce the
      incidence of the patellar clunk, especially in the posterior substituted designs.
      METHODS: 130 total knee replacements performed using the enhanced PS femoral
      components were followed-up with clinical and radiographic evaluations. RESULTS:
      Patellar clunk was seen in 3 of the 130 knees (2%). This is much less than the
      incidence of patellar clunk reported until now. CONCLUSIONS: Removal of the sharp
      ridge in the intercondylar groove in the newer implant seems to have been
      effective in reducing the incidence of the patellar clunk. It also indicates that
      the sharp ridge was the most probable cause of the clunk.

PMID- 25983501
TI  - Neglected post burns contracture of hand in children: Analysis of contributory
      socio-cultural factors and the impact of neglect on outcome.
AB  - BACKGROUND: No study has ever evaluated the causes and effect of neglect on the
      outcome of post burns contractures of hand in children. METHODS: 66 hands in 61
      children (mean age 12.22 years) with a mean neglect of 11.6 years (range 5-17
      years) were assessed for the causes of neglect and the outcome of surgery.
      Average follow up was 6.6 years. The results were assessed in two groups of 5-10
      years neglect as group I and >10 years neglect as group II. RESULTS: In a total
      number of 134 contracted rays in 66 hands, the surgical procedures included local
      Z/V-Y flap (51 rays), cross finger flap (48 rays), full thickness graft (35
      rays). Additional external fixator with a distracter was used in 3 patients
      treated at a delay of 14, 16 and 17 years. 50 (81.96%) patients belonged to rural
      and slum areas. The reasons for delayed treatment included poverty - 33 patients,
      lack of awareness of surgical treatment - 16 patients; and indifference of
      parents - 12 patients. 44 (72.13%) children were illiterates. With treatment the
      average DASH score improved from 65.10 to 36.90 (p < .000) and from 68.14 to
      45.93 (p < .000) in group I and II respectively. The results were significantly
      superior in group I (p < .000). CONCLUSION: The main factors for neglect in
      treatment of post burns contracture include poverty, lack of awareness and
      illiteracy. All the patients showed significant improvement in function after the
      surgery. Contractures with higher neglect had significantly inferior outcome.

PMID- 25983502
TI  - Risk factors in cervical spondylosis.
AB  - BACKGROUND: Cervical spondylosis is essentially a degenerative disorder common
      after fourth decade. It has been seen that radiological evidence of cervical
      spondylosis do not necessarily co-relate with clinical findings. This discrepancy
      has been attributed to the morphometric dimensions of the vertebrae, age, sex,
      race, occupation, weight and height of the patients. OBJECTIVE: The objective of
      this study is to co-relate the variables like age, sex, race, occupation,
      vertebral body diameter, canal diameter, canal body ratio of cervical spine
      vertebrae with cervical spondylosis cases with normal population. METHODS: In
      this hospital based, case control, consent based, cross-sectional, clinico
      radiological study 200 individuals (controls-100, cases-100) who were subjected
      to lateral projection radiographs of cervical spine. Their age, sex, race,
      occupation, height, weight and mid-sagittal canal diameter (CD), sagittal
      vertebral body diameter (VBD) and the canal-body ratio (CBR) of the cervical
      vertebrae was recorded and analyzed statistically. RESULTS: There was no relation
      between vertebral dimensions and clinical groups. In radiculopathy group, age and
      height showed significance on univariate analysis. While only age remained
      significant on multivariate analysis. In neck pain group age, sex, and height
      showed significance on univariate analysis while in multivariate analysis age,
      sex and occupation were significant risk factors.

PMID- 25983503
TI  - Sports injury pattern in school going children in Union Territory of Chandigarh.
AB  - OBJECTIVE: To determine incidence of various types of sport injuries and other
      associated factors, among competitive sports playing school children of
      Chandigarh. DESIGN: This study is a survey based study, and spanned for a period
      of one year. School going students in age group 11-18 years of Chandigarh (Union
      Territory) India, who were in competitive sports, were included for this survey
      after taking informed consent from concerned school authorities. 33 schools
      consisting of 36.165 students were analysed in the study, 7230 students were
      found to participate in 40 different categories of sports. RESULTS: Total of 246
      filled questionnaires were analyzed making it an injury frequency of 3.40% among
      7230 participating young athletes in 12 months study duration. Estimated
      incidence rate, considering hours of exposure in practice, came out to be 48.07
      injuries per 1000 h of exposure in practice among 246 injured cases. 40.2% of the
      injured children (99/246) attributed their injury to poor ground condition while
      other 30.5% (75/246) to faulty techniques. Rest attributed their injuries to poor
      fitness levels, improper use of equipment and other reasons. Of the 33 schools
      surveyed, 27.3% (9/33) had a doctor as health professional, 9.1% (2/33) had a
      physiotherapist while 66.6% of the schools (22/33) had no health care
      professional. CONCLUSION: The incidence of sports injuries in the region is high
      as compared to the global data. The findings has highlighted the need for a
      nationwide surveillance system and then taking appropriate measures for future
      injury prevention and appropriate management.

PMID- 25983504
TI  - Is distal locking of long nails for intertrochanteric fractures necessary? A
      clinical study.
AB  - BACKGROUND: Few clinical studies have examined the utility of distal interlocking
      nails when fixing intertrochanteric fractures with intramedullary devices. In
      this study we performed a retrospective analysis comparing fixation method of
      intertrochanteric fractures with either a long unlocked cephalomedullary nail
      versus a long locked cephalomedullary nail. Our hypothesis was there would be no
      difference in device related failures or complications in stable
      intertrochanteric fractures treated with long locked or long unlocked
      cephalomedullary nails. METHODS: A retrospective chart review was performed of
      all stable intertrochanteric fractures treated with a long cephalomedullary nail
      between 2006 and 2012 at our institution. Clinical history as well as
      perioperative radiography was carefully reviewed for all subjects. AO
      classification, the use of locked or unlocked technique, and failure status was
      recorded. RESULTS: Overall, a device related failure rate of 1.8% (2/107) was
      observed for stable intertrochanteric fractures treated with long
      cephalomedullary nails. No statistical difference in failure rate was found
      between locked and unlocked nails within our studied population (0% long locked
      (0/56) versus 3.9% long unlocked (2/51), p = 0.224). CONCLUSION: This clinical
      study supports our hypothesis that long cephalomedullary nails do not need to be
      locked for stable intertrochanteric fractures. We found no difference in failure
      rates between the two approaches across 107 patients.

PMID- 25983505
TI  - Is there a safe zone to avoid superficial radial nerve injury with Kirschner wire
      fixation in the treatment of distal radius? A cadaveric study.
AB  - AIM OF THE STUDY: To determine the relation of the superficial radial nerve to
      bony land-marks and to identify a safe zone for K-wire pinning in the distal
      radius. METHOD: The superficial radial nerve was dissected in sixteen upper
      extremities of preserved cadavers. RESULTS: We found that the superficial radial
      nerve emerged from under brachioradialis at a mean distance of 8.45 (+/-1.22) cm
      proximal to the radial styloid. The mean distance from the first major branching
      point of the superficial radial nerve to the radial styloid were 4.8 +/- 0.4 cm.
      All branches of the superficial radial nerve were found to lie in the radial half
      of an isosceles triangle formed by the radial styloid, Lister's tubercle and the
      exit point of the superficial radial nerve. There is an elliptical area just
      proximal to the Lister's tubercle. This area is not crossed by any tendons or
      nerve. It is bounded by the extensor carpiradialis brevis, extensor pollicis
      longus. CONCLUSION: Pinning through the radial styloid is unsafe as the branches
      of the superficial radial nerve passe close to it. The ulnar half of the
      isosceles triangle is safe regarding the nerve. The elliptical zone just proximal
      to the Lister's tubercle is safe regarding the tendons and nerve.

PMID- 25983506
TI  - Habitual dislocation of patella: A review.
AB  - Habitual dislocation of patella is a condition where the patella dislocates
      whenever the knee is flexed and spontaneously relocates with extension of the
      knee. It is also termed as obligatory dislocation as the patella dislocates
      completely with each flexion and extension cycle of the knee and the patient has
      no control over the patella dislocating as he or she moves the knee(1). It
      usually presents after the child starts to walk, and is often well tolerated in
      children, if it is not painful. However it may present in childhood with
      dysfunction and instability. Very little literature is available on habitual
      dislocation of patella as most of the studies have combined cases of recurrent
      dislocation with habitual dislocation. Many different surgical techniques have
      been described in the literature for the treatment of habitual dislocation of
      patella. No single procedure is fully effective in the surgical treatment of
      habitual dislocation of patella and a combination of procedures is recommended. 

PMID- 25983507
TI  - Miniarthrotomy assisted percutaneous screw fixation for displaced medial
      malleolus fractures - A novel technique.
AB  - AIM: To describe here a technique of miniarthrotomy assisted percutaneous screw
      insertion for displaced Herscovici type B and C medial malleolar fractures.
      METHOD: Incision was made centred over the superomedial angle of the ankle
      mortise, about half a cm medial to tibialis anterior. Arthrotomy was done and
      reduction obtained. Percuntaneously, two 4 mm cancellous cannulated screws were
      inserted through medial malleolus. RESULTS AND CONCLUSION: This approach allows
      direct visualization of reduction, removal of entrapped soft tissue and
      preservation of saphenous vein and nerve.

PMID- 25983508
TI  - Osteosarcoma in identical twins: A case report.
AB  - Osteosarcoma (OS) is the most frequent primary malignant bone tumor, if we
      exclude myeloma, a hematologic systemic disease. OS is relatively uncommon, with
      an estimated incidence of 600 cases per year in the United States. Among siblings
      is an even rarer phenomenon, with scattered reports throughout the English
      literature(1). We report the incidence of OS in identical twins. The first case
      is a low-grade OS arisen in the proximal tibia of a 25-year-old man, treated with
      en-bloc resection and reconstruction with allograft. The second one is a high
      grade OS of the distal tibia of the 33-year-old twin, developed in a previous non
      ossifying fibroma (NOF) followed over the time. The patient was treated with neo
      adjuvant chemotherapy, en-bloc resection and reconstruction with allograft. Our
      literature review did not find any case of OS in identical twins, while 26
      reports of OS in siblings are described. 

PMID- 25983509
TI  - Non-traumatic myositis ossificans circumscripta: A diagnosis trap.
AB  - Myositis ossificans circumscripta (MOC) is a benign condition of non-neoplastic
      heterotopic bone formation in the muscle or soft tissue. Trauma plays a role in
      the development of MOC, thus, non-traumatic MOC is very rare. Although MOC may
      occur anywhere in the body, the lesions are localized predominantly in the high
      risk sites of injury, such as the thigh, buttock, and elbow. MOC can easily be
      mistaken for osteomyelitis or a malignant tumor, specifically osteosarcoma or
      soft-tissue sarcoma. We report a rare case of non-traumatic myositis ossificans
      circumscripta of thigh which appear clinically and radiologically as a malignant
      neoplasm. Despite its rarity, MOC should be contemplated in the differential
      diagnosis of malignant tumors. 

PMID- 25983510
TI  - Plant thorn synovitis of elbow in children.
AB  - Four rare cases of plant thorn synovitis of left elbow were admitted at our
      institution, which were initially misdiagnosed as partially treated septic
      arthritis of elbow or Juvenile inflammatory arthritis. All of them were of
      paediatric age group. Symptoms included pain, swelling, and decreased range of
      motion of affected joint. On examination synovitis was present in all patients.
      Roentgenograms & Ultrasonography were inconclusive in all patients, Definitive
      diagnosis was made only after arthrotomy, Thorn fragments (Acacia arabica) were
      recovered from the hypertrophied synovium & subtotal synovectomy was done and
      sent for histopathological examination. All patients improved after surgery with
      mean residual flexion deformity of 12.5 +/- 2.86 degrees . Plant thorn induced
      synovitis of elbow is rare, it must be included in the differential diagnosis of
      monoarthritis of elbow and a high index of suspicion is needed for retained thorn
      fragments in elbow joint causing synovitis. Its optimal treatment is arthrotomy,
      foreign body removal and total/subtotal synovectomy. 

PMID- 25983511
TI  - Ossification of the discoid meniscus: A case report.
AB  - Meniscal ossification, or bone formation within the substance of the meniscus, is
      a rare entity. Magnetic resonance imaging allows the unequivocal diagnosis of a
      meniscal ossification. We aimed to present a case of discoid meniscal
      ossification, which is quite rare, with the emphasis on imaging findings. 

PMID- 25983512
TI  - "A 40-year-old female with painless, slow growing prepatellar mass".
AB  - A 40-year-old woman from India presented with a mass in the front of her left
      knee which had been present for 8 months. Local examination revealed a globular
      mass of approximate size 5 cm * 4 cm * 4 cm in front of the lower pole of left
      patella. The patient was investigated with imaging studies and laboratory tests.
      Plain radiograph of the chest was normal. In addition, contrast enhanced Magnetic
      Resonance Imaging (MRI) of the left knee was performed. Based on the history,
      physical examination, laboratory and imaging studies, what is the differential
      diagnosis? 

PMID- 25983513
TI  - Evaluation of pain in bilateral total knee replacement with and without
      tourniquet; a prospective randomized control trial.
AB  - AIM: Thigh pain following tourniquet application is a common complaint in early
      post operative period following total knee arthroplasty. METHOD: Post operative
      Thigh pain was evaluated in 30 consecutive simultaneous bilateral total knee
      arthroplasty patients between July 2013 and January 2014. Patient thigh pain was
      evaluated with the VAS score. The scale was applied on first, second, third day &
      second and six weeks after surgery. RESULT: There were statistically significant
      difference in VAS score in non-tourniquet group on first, second, third post
      operative day. We did not find statistically significant difference at Second and
      Six weeks post operatively. CONCLUSION: This Randomized trial demonstrates that
      non-tourniquet use in TKA has less early postoperative pain and leads to better
      recovery.

PMID- 25983514
TI  - Recovery of knee function in the isolated MCL and combined ACL-MCL deficient
      knee.
AB  - BACKGROUND: The MCL is the prime medial stabiliser of the knee and is a commonly
      injured structure which leads to valgus instability of the knee. OBJECTIVES: We
      aim to analyse differences in recovery of knee motion and muscle function over
      one year follow up in the isolated MCL and combined ACL-MCL injured knee. We
      hypothesized that combined ACL-MCL injuries lead to greater knee motion and
      muscle function deficits at 1 year. METHODS: Isolated MCL (Group I) or combined
      ACL-MCL injuries (Group II) from 2006-2010 were included. Those with a previous
      MCL injury, injury to contralateral limb or presenting 2 weeks post-injury were
      excluded. At certain outpatient follow up intervals, we recorded pre-determined
      parameters of knee function. Follow-up was at weeks 2, 6, 12, 26, 52. RESULTS:
      The cohort included 82 patients (54 males:28 females) with a mean age of 32
      (range 16-56). Group II showed a deficit in Total Range of Movement (TROM) and
      flexion at 6 month follow up (p < 0.05). Group II showed an extension deficit at
      week 2 (p < 0.05). The Peak Torque Deficit (PTD) and Average Power Deficit (APD)
      improved for quadriceps and hamstrings across all follow up intervals (p > 0.05).
      CONCLUSION: There is a TROM and flexion deficit at 6 months in group II,
      resolving by 1 year. There was no difference in PTD or APD in either group.

PMID- 25983515
TI  - Acetabular fractures labelled poor surgical choices: Analysis of operative
      outcome.
AB  - PURPOSE: We report the surgical outcome in 52 patients with acetabular otherwise
      considered as poor surgical choices. METHODS: 43 male and 9 female patients were
      operated at a mean age of 43 years and followed up for a mean duration of 60.3
      months. There were 22 elementary fractures and 31 associated ones according to
      Letournal and Judet classification. Osteosynthesis was attempted in 48 patients
      whereas a primary total hip arthroplasty was performed in 4 patients. Outcome was
      assessed radiologically and functionally employing Harris Hip Score (HHS).
      RESULTS: Average HHS in osteosynthesis group was 82.56 +/- 12.4 with excellent to
      good results in 59.6% of the cases. Symptomatic osteoarthritis occurred in 13.5%
      of cases, avascular necrosis and severe heterotopic ossification in 7.7% each,
      infection and nerve palsy in 11.5% each. CONCLUSION: Although the complication
      rates in this series is marginally more than that reported in literature, we
      recommend that the indications of surgical fixation in acetabular fractures need
      to be extended to those which were considered poor surgical choices.

PMID- 25983516
TI  - Scurvy in pediatric age group - A disease often forgotten?
AB  - Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare
      as compared to other nutritional deficiencies, it is seldom suspected and this
      frequently leads to delayed recognition of this disorder. Children with abnormal
      dietary habits, mental illness or physical disabilities are prone to develop this
      disease. The disease spectrum of scurvy is quite varied and includes
      dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma,
      ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal
      slips are common radiological findings. High index of suspicion, detailed history
      and bilateral limb radiographs aids physician in diagnosing this eternal
      masquerader. We searched Pubmed for recent literature (2009-2014) with search
      terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and
      children" "scurvy and pediatric age group". There were a total of 36 articles
      relevant to pediatric scurvy in children (7 reviews and 29 case reports) which
      were retrieved. The review briefly recapitulates the role of vitamin C, the
      various disease manifestations and the treatment of scurvy to create awareness of
      the disease which still is reported from our country, although sporadically. The
      recent advances related to scurvy and its management in pediatric age group are
      also incorporated. 

PMID- 25983518
TI  - Total knee replacement in triple deformity with posterior subluxation of the knee
      joint.
AB  - Dislocation or subluxation following total knee arthroplasty has been extensively
      reported, but vice versa that is total knee replacement for subluxed or
      dislocated knee has not been published. Triple deformity of knee that is flexion,
      external rotation, valgus at knee associated with posterior subluxation of tibia
      occurs in rheumatoid arthritis, advanced tubercular arthritis and neglected
      posttraumatic residual dislocated knee. A 50 year old female with seropositive
      rheumatoid arthritis had the above disabling deformity in left lower limb and
      varus with medial tibial thrust in the other. Bilateral total knee arthroplasty
      was planned. Conservative method of reduction of left knee posterior subluxation
      preoperatively by 90-90 skeletal traction failed; hence patient was subjected to
      a staged bilateral total knee replacement using an innovative technique. The most
      difficult and determining initial surgical step of knee replacement in such
      dislocated/subluxed knee is reduction of posterior subluxation and gaining
      flexion at knee, as only after gaining flexion and reducing dislocated tibia,
      will we be able to do knee arthroplasty in triple deformity of knee. These knees
      are grossly unstable as most of the capsule-ligamentous structures are
      attritioned/non-existent. So, a fine balance of bone cuts and soft-tissue release
      needs to be done in a sequential manner to fine tune valgus and posterior
      subluxation correction without jeoparadising neurovascular structures. After 3
      years of knee arthroplasty the patient has painless, stable knee with good range
      of motion and is able to do all her activities, of living in a hilly terrain. 

PMID- 25983517
TI  - Polyethylene in knee arthroplasty: A review.
AB  - Polyethylene (PE) has been used extensively in knee arthroplasty since the mid
      20th century. Progress in material manufacturing and processing has led to newer
      polyethylenes over last few decades with different material properties. It has
      been established that PE wear in knee arthroplasty causes particle induced
      osteolysis which is the main reason for late failure and requires revision
      surgery. Although there are various causes of wear, the properties of PE have
      long been a matter of investigation as a contributory factor. The advent of newer
      highly cross linked PE has been shown to improve wear rates in hip arthroplasty
      but the benefits have not been shown to be of the same degree in knee
      arthroplasty. The laboratory and clinical studies so far are limited and slightly
      conflicting in their conclusions. The risks of using highly cross linked PE in
      knee arthroplasty include tibial post fracture, disruption of locking mechanism,
      liner fracture which can lead to increased wear and osteolysis. The current
      evidence suggests that highly cross linked polyethylenes should be used with
      caution and only considered in younger active patients. The results of a recently
      completed randomized trial to compare the conventional with high molecular weight
      PE in knee arthroplasty are awaited. 

PMID- 25983519
TI  - Acquired permanent dislocation of the patella in a patient with rheumatoid genu
      valgum.
AB  - A case of acquired permanent dislocation of the patella associated with severe
      genu valgum in a patient with rheumatoid arthritis (RA) is herein reported. The
      pain and genu valgum progressed because of poor RA control. The patient had no
      history of major trauma of the knee before or after the onset of RA. The most
      reasonable hypothesis to explain this patient's pathology is that occult patellar
      dislocation developed after a minor trauma and progressed to permanent
      dislocation; poor RA control then worsened both the patellar dislocation and genu
      valgum. Total knee arthroplasty (TKA) with patella reduction was successfully
      performed with release of the lateral retinaculum and extension of the extensor
      mechanism by partial snipping of the rectus femoris tendon. Two years after the
      operation, the patient exhibited improvement in her Knee Society Knee and
      Function Scores from preoperative scores of 18 and 20 to postoperative scores of
      94 and 80, respectively. Acquired permanent dislocation of the patella associated
      with severe genu valgum in patients with RA is rare. Excellent results were
      obtained with TKA, and the proximal realignment method was a useful procedure for
      patella reduction. 

PMID- 25983520
TI  - Coxa saltans caused by extraarticular synovial chondromatosis overlying an
      isolated osteochondroma of the greater trochanter: A rare aetiology.
AB  - Snapping hip is produced by intraarticular and extraarticular pathology. We
      describe a rare case of extraarticular snapping hip caused by bursal synovial
      chondromatosis overlying an osteochondroma. A 32-year-old male presented with
      swelling in his right gluteal region for 6 years associated with pain and
      snapping on movements since three months. On examination, he had an ill-defined
      10 * 6 cm swelling over the posterolateral aspect of the greater trochanter.
      Plain radiographs revealed an osteochondroma arising from the greater trochanter.
      Further imaging showed exostosis with possible haemangioma, lipoma or liquefied
      haematoma overlying it. We proceeded with excision biopsy and intraoperatively
      found a bursa with synovial chondromatosis overlying the exostosis. At the end of
      ten months follow up, patient was asymptomatic and had no snapping. We present
      this case for its rarity, clinical and radiological diagnostic challenges and for
      its unique presentation. 

PMID- 25983521
TI  - Bilateral lipoma arborescens with osteoarthritis knee: Case report and literature
      review.
AB  - Lipoma arborescens is villous proliferation of synovium and is often unilateral
      in the absence of any systemic disease. We report a case of 54 year old male
      presenting with bilateral lipoma arborescens associated with osteoarthritis. The
      diagnosis is often difficult due to similar symptomatology of lipoma arborescens
      and osteoarthritis. 

PMID- 25983522
TI  - Tardy ulnar nerve palsy after fracture non-union medial epicondyle of humerus -
      An unusual case.
AB  - Tardy ulnar nerve palsy is a chronic clinical condition characterised by delayed
      onset ulnar neuropathy. Typically tardy ulnar nerve palsy occurs as a consequence
      of non-union of lateral condyle in child resulting in cubitus valgus deformity
      which ultimately is the cause of ulnar nerve palsy. However very few literature
      are available for tardy ulnar nerve palsy as a result of old fracture of medial
      epicondyle without cubitus varus or valgus deformity. We report a rare case of
      tardy ulnar nerve in an adult male with fracture non-union of medial epicondyle
      of humerus. 

PMID- 25983523
TI  - A rare case of giant cell tumour arising from anterior cruciate ligament: Its
      diagnosis and management.
AB  - Tenosynovial giant cell tumour is a locally aggressive tumour arising from the
      synovia of the fibrous tissue surrounding the joints, tendon sheaths and tendons.
      Areas of predilection are the hand, and in the case of synovial joints, the knee
      joint is particularly affected. We describe a rare case of an intra-articular
      localized tenosynovial giant cell tumour arising from the anterior cruciate
      ligament (ACL) in a 27 year male who presented with pain and giving way of his
      left knee without prior history of any trauma. Tests for internal derangement of
      knee were negative. MRI reported an ACL tear with a heterogeneous fibrous mass
      attached to the distal part, most probably an organized haematoma. It was decided
      to do a diagnostic arthroscopy before proceeding for ACL reconstruction.
      Arthroscopy revealed a purple coloured mass attached to distal part of ACL. The
      mass was removed piecemeal using an additional posterolateral portal. ACL was
      found intact. Histopathology reported it to be tenosynovial giant cell tumour.
      The patient was asymptomatic at each subsequent follow up. It is a rare diagnosis
      which presented as an ACL tear; in such suspected cases it is prudent to perform
      a diagnostic arthroscopy before going for ACL reconstruction. 

PMID- 25983524
TI  - Reliable and reproducible technique to mark center of ankle in total knee
      arthroplasty.
AB  - AIM: Bony and soft tissue landmarks have been used in the past to determine the
      center of the ankle to facilitate the tibial cut using an extramedullary guide in
      total knee arthroplasty. However literature reports are scanty in regards to the
      most ideal method available and its reproducibility in marking the center of the
      ankle intra-operatively. METHODS: We describe a method of using an
      electrocardiogram (ECG) lead in determining the center of the ankle, thus
      facilitating the alignment of the extramedullary guide for the tibia. RESULTS:
      Using this technique, in our study the mean lateral tibial component angle was
      90.09(84.2 degrees -94.3 degrees ). The number of knees in the range of 88
      degrees -92.4 degrees  were 120 out of 122 knees (98.40%). CONCLUSION: The
      described method is reliable and cheap, with reproducibility in determining the
      tibial cut in total knee arthroplasty.

PMID- 25983526
TI  - Cumulative effects of land use on fish metrics in different types of running
      waters in Austria.
AB  - The catchment land-use composition of 249 fish sampling sites in Austrian running
      waters revealed effects on the biological integrity. Beyond correlative analysis,
      we investigated (1) which land-use category had the strongest effect on fish, (2)
      whether metrics of functional fish guilds reacted differently, (3) whether there
      were cumulative effects of land-use categories, and (4) whether effects varied in
      strength across river types. We fed 5 land-use categories into regression trees
      to predict the European Fish Index or fish metric of intolerant species (mainly
      Salmo trutta fario). Agriculture and urbanisation were the best predictors and
      indicated significant effects at levels of >23.3 and >2%, respectively. Model
      performance was R2 = 0.15 with the Fish Index and R2 = 0.46 with intolerant
      species. The tree structure showed a cumulative effect from agriculture and
      urbanisation. For the intolerant species metric, a combination of high
      percentages for agriculture and urbanisation was related to moderate status,
      whereas <7.3% agriculture were related to good status, although urbanisation was
      higher than 1.8%. Headwater river types showed stronger responses to land use
      than river types of lower gradient and turned out to be more sensitive to
      urbanisation than agriculture.

PMID- 25983525
TI  - Regenerative Engineering and Bionic Limbs.
AB  - Amputations of the upper extremity are severely debilitating, current treatments
      support very basic limb movement, and patients undergo extensive physiotherapy
      and psychological counselling. There is no prosthesis that allows the amputees
      near-normal function. With increasing number of amputees due to injuries
      sustained in accidents, natural calamities and international conflicts, there is
      a growing requirement for novel strategies and new discoveries. Advances have
      been made in technological, material and in prosthesis integration where
      researchers are now exploring artificial prosthesis that integrate with the
      residual tissues and function based on signal impulses received from the residual
      nerves. Efforts are focused on challenging experts in different disciplines to
      integrate ideas and technologies to allow for the regeneration of injured
      tissues, recording on tissue signals and feed-back to facilitate responsive
      movements and gradations of muscle force. A fully functional replacement and
      regenerative or integrated prosthesis will rely on interface of biological
      process with robotic systems to allow individual control of movement such as at
      the elbow, forearm, digits and thumb in the upper extremity. Regenerative
      engineering focused on the regeneration of complex tissue and organ systems will
      be realized by the cross-fertilization of advances over the past thirty years in
      the fields of tissue engineering, nanotechnology, stem cell science, and
      developmental biology. The convergence of toolboxes crated within each discipline
      will allow interdisciplinary teams from engineering, science, and medicine to
      realize new strategies, mergers of disparate technologies, such as biophysics,
      smart bionics, and the healing power of the mind. Tackling the clinical
      challenges, interfacing the biological process with bionic technologies,
      engineering biological control of the electronic systems, and feed-back will be
      the important goals in regenerative engineering over the next two decades.

PMID- 25983527
TI  - Low Friction CrNMPP/TiNDCMS Multilayer Coatings.
AB  - Transition metal nitrides like CrN and TiN are widely used in automotive
      applications due to their high hardness and wear resistance. Recently, we showed
      that a multilayer architecture of CrN and TiN, deposited using the hybrid-high
      power impulse magnetron sputtering (HIPIMS) and direct current magnetron
      sputtering (DCMS)-HIPIMS/DCMS deposition technique, results in coatings which
      indicate not only increased mechanical and tribological properties but also
      friction coefficients in the range of diamond-like-carbon coatings when tested at
      RT and ambient air conditions. The modulated pulsed power (MPP) deposition
      technique was used to replace the HIPIMS powered cathode within this study to
      allow for a higher deposition rate, which is based on the complex MPP pulse
      configuration. Our results on MPP/DCMS deposited CrN/TiN multilayer coatings
      indicate excellent mechanical and tribological properties, comparable to those
      obtained for HIPIMS/DCMS. Hardness values are around 25 GPa with wear rates in
      the range of 2 * 10-16 Nm/m3 and a coefficient of friction around 0.05 when
      preparing a superlattice structure. The low friction values can directly be
      correlated to the relative humidity in the ambient air during dry sliding
      testing. A minimum relative humidity of 13% is necessary to guarantee such low
      friction values, as confirmed by repeated tests, which are even obtained after
      vacuum annealing to 700  degrees C. Our results demonstrate that the co
      sputtering of high metal ion sputtering techniques and conventional DC sputtering
      opens a new field of applications for CrN/TiN coatings as high wear resistance
      and low friction coatings.

PMID- 25983528
TI  - Let's See a Boy and a Balloon: Argument Labels and Syntactic Frame in Verb
      Learning.
AB  - It is by now well established that toddlers use the linguistic context in which a
      new word-and particularly a new verb-appears to discover aspects of its meaning.
      But what aspects of the linguistic context are most useful? To begin to
      investigate this, we ask how 2-year-olds use two sources of linguistic
      information that are known to be useful to older children and adults in verb
      guessing tasks: syntactic frame, and the semantic content available in the noun
      phrases labeling the verb's arguments. We manipulate the linguistic contexts in
      which we present novel verbs to see how they use these two sources of
      information, both separately and in combination, to acquire the verb's meaning.
      Our results reveal that like older children and adults, toddlers make use of both
      syntactic frame and semantically contentful argument labels to acquire verb
      meaning. But toddlers also require these two sources of information to be
      packaged in a particular way, into a single sentence that identifies 'who did
      what to whom.'

PMID- 25983529
TI  - Considerations of a Dual-systems Model of Cognitive Development and Risky
      Driving.
AB  - The dual-systems model of adolescent risk-taking postulates that risk-taking
      during adolescence partially results from an imbalance in the development of the
      executive and the socio-emotional cognitive systems. While supported by
      behavioral and neuroanatomical data, translational research linking the model
      with real-world driving or laboratory driving simulation is sparse. This paper
      discusses the model as it relates to adolescent driving and reviews empirical
      studies that have applied it in a driving-specific context. While, the studies
      reviewed provided partial support, each lacked a critical component necessary to
      fully test the model. Thus, a strong test has yet to be implemented; however, the
      dual-systems model holds promise for advancing the understanding of teen driving
      risk and guiding applications for prevention and policy.

PMID- 25983532
TI  - The Story of Kyle.

PMID- 25983533
TI  - Cancer Survivorship Care: Summarizing the 6 Tools for Success.
AB  - With nearly 12 million cancer survivors living in the United States today
      including those receiving care within the VHA-attention is quickly shifting
      toward care of the cancer survivor. Although challenging, these authors offer
      essential tools for long-term management of this fast-growing population.

PMID- 25983531
TI  - Regulatory Considerations for the Clinical and Research Use of Transcranial
      Direct Current Stimulation (tDCS): review and recommendations from an expert
      panel.
AB  - The field of transcranial electrical stimulation (tES) has experienced
      significant growth in the past 15 years. One of the tES techniques leading this
      increased interest is transcranial direct current stimulation (tDCS). Significant
      research efforts have been devoted to determining the clinical potential of tDCS
      in humans. Despite the promising results obtained with tDCS in basic and clinical
      neuroscience, further progress has been impeded by a lack of clarity on
      international regulatory pathways. We therefore convened a group of research and
      clinician experts on tDCS to review the research and clinical use of tDCS. In
      this report, we review the regulatory status of tDCS, and we summarize the
      results according to research, off-label and compassionate use of tDCS in the
      following countries: Australia, Brazil, France, Germany, India, Iran, Italy,
      Portugal, South Korea, Taiwan and United States. Research use, off label
      treatment and compassionate use of tDCS are employed in most of the countries
      reviewed in this study. It is critical that a global or local effort is organized
      to pursue definite evidence to either approve and regulate or restrict the use of
      tDCS in clinical practice on the basis of adequate randomized controlled
      treatment trials.

PMID- 25983534
TI  - Managing Health Care After Cancer Treatment: A Wellness Plan.
AB  - Many patients and health care providers lack awareness of both the existence of,
      and treatments for, lingering distress and disability after treatment. A cancer
      survivorship wellness plan can help ensure that any referral needs for
      psychosocial and other restorative care after cancer treatment are identified.

PMID- 25983535
TI  - Autofocusing for Microscopic Images using Harris Corner Response Measure.
AB  - One of the difficulties for proper imaging in microscopic image analysis is
      defocusing. Microscopic images such as cellular images, protein images, etc. need
      properly focused image for image analysis. A small difference in focal depth
      affects the details of an object significantly. In this paper, we introduce a
      novel auto-focusing approach based on Harris Corner Response Measure (HCRM) and
      compare the performance with some existing auto-focusing methods. We perform our
      experiments on protein images as well as a simulated image stack to evaluate the
      performance of our method. Our results show that our HCRM-based technique
      outperforms other techniques.

PMID- 25983536
TI  - Environmental conditions and biotic interactions acting together promote
      phylogenetic randomness in semi-arid plant communities: new methods help to avoid
      misleading conclusions.
AB  - QUESTIONS: Molecular phylogenies are being increasingly used to better understand
      the mechanisms structuring natural communities. The prevalent theory is that
      environmental factors and biotic interactions promote the phylogenetic clustering
      and overdispersion of plant communities, respectively. However, both
      environmental filtering and biotic interactions are very likely to interact in
      most natural communities, jointly affecting community phylogenetic structure. We
      asked the following question: How do environmental filters and biotic
      interactions jointly affect the phylogenetic structure of plant communities
      across environmental gradients? LOCATION: Eleven Stipa tenacissima L. grasslands
      located along an environmental gradient from central to south-east Spain, which
      covers the core of the distribution area of this vegetation type in Europe.
      METHODS: We jointly evaluated the effects of environmental conditions and plant
      plant interactions on the phylogenetic structure -measured with the mean
      phylogenetic distance index- of the studied communities. As an indicator of
      environmental conditions, we used a PCA ordination including eight climatic
      variables. Different metrics were used to measure the following processes: i)
      competition/facilitation shifts at the entire community level (Species
      Combination index), and ii) the effect of the microclimatic amelioration provided
      by the two most important nurses on neighbours composition (similarity indices
      and comparison of the phylogenetic pattern between canopy patches and bare ground
      areas). RESULTS: Biotic interactions and, to a less extent, environmental
      conditions, affected the phylogenetic pattern of the studied communities. While
      positive plant-plant interactions (both at the community and the scale of
      individual nurses) increased phylogenetic overdispersion, higher rainfall
      increased phylogenetic clustering. The opposed effects of environmental
      conditions and biotic interactions could be the main cause of the overall random
      phylogenetic structure found in most of these communities. CONCLUSIONS: Our
      results illustrate, for the first time, how an overall random phylogenetic
      pattern may not be promoted only by the lack of influence of either environmental
      filtering or biotic interactions, but rather by their joint and opposing effects.
      They caution about making inferences about the underlying mechanisms shaping
      plant communities from the sole use of their phylogenetic pattern. We also
      provide a comprehensive set of easy-to-measure tools to avoid misleading
      conclusions when interpreting phylogenetic structure data obtained from
      observational studies.

PMID- 25983537
TI  - Empirical Transition Probability Indexing Sparse-Coding Belief Propagation (ETPI
      SCoBeP) Genome Sequence Alignment.
AB  - The advance in human genome sequencing technology has significantly reduced the
      cost of data generation and overwhelms the computing capability of sequence
      analysis. Efficiency, efficacy, and scalability remain challenging in sequence
      alignment, which is an important and foundational operation for genome data
      analysis. In this paper, we propose a two-stage approach to tackle this problem.
      In the preprocessing step, we match blocks of reference and target sequences
      based on the similarities between their empirical transition probability
      distributions using belief propagation. We then conduct a refined match using our
      recently published sparse-coding belief propagation (SCoBeP) technique. Our
      experimental results demonstrated robustness in nucleotide sequence alignment,
      and our results are competitive to those of the SOAP aligner and the BWA
      algorithm. Moreover, compared to SCoBeP alignment, the proposed technique can
      handle sequences of much longer lengths. 

PMID- 25983538
TI  - PathoQC: Computationally Efficient Read Preprocessing and Quality Control for
      High-Throughput Sequencing Data Sets.
AB  - Quality control and read preprocessing are critical steps in the analysis of data
      sets generated from high-throughput genomic screens. In the most extreme cases,
      improper preprocessing can negatively affect downstream analyses and may lead to
      incorrect biological conclusions. Here, we present PathoQC, a streamlined toolkit
      that seamlessly combines the benefits of several popular quality control software
      approaches for preprocessing next-generation sequencing data. PathoQC provides a
      variety of quality control options appropriate for most high-throughput
      sequencing applications. PathoQC is primarily developed as a module in the
      PathoScope software suite for metagenomic analysis. However, PathoQC is also
      available as an open-source Python module that can run as a stand-alone
      application or can be easily integrated into any bioinformatics workflow. PathoQC
      achieves high performance by supporting parallel computation and is an effective
      tool that removes technical sequencing artifacts and facilitates robust
      downstream analysis. The PathoQC software package is available at
      http://sourceforge.net/projects/PathoScope/. 

PMID- 25983539
TI  - Next generation distributed computing for cancer research.
AB  - Advances in next generation sequencing (NGS) and mass spectrometry (MS)
      technologies have provided many new opportunities and angles for extending the
      scope of translational cancer research while creating tremendous challenges in
      data management and analysis. The resulting informatics challenge is invariably
      not amenable to the use of traditional computing models. Recent advances in
      scalable computing and associated infrastructure, particularly distributed
      computing for Big Data, can provide solutions for addressing these challenges. In
      this review, the next generation of distributed computing technologies that can
      address these informatics problems is described from the perspective of three key
      components of a computational platform, namely computing, data storage and
      management, and networking. A broad overview of scalable computing is provided to
      set the context for a detailed description of Hadoop, a technology that is being
      rapidly adopted for large-scale distributed computing. A proof-of-concept Hadoop
      cluster, set up for performance benchmarking of NGS read alignment, is described
      as an example of how to work with Hadoop. Finally, Hadoop is compared with a
      number of other current technologies for distributed computing. 

PMID- 25983540
TI  - Computing molecular signatures as optima of a bi-objective function: method and
      application to prediction in oncogenomics.
AB  - BACKGROUND: Filter feature selection methods compute molecular signatures by
      selecting subsets of genes in the ranking of a valuation function. The
      motivations of the valuation functions choice are almost always clearly stated,
      but those for selecting the genes according to their ranking are hardly ever
      explicit. METHOD: We addressed the computation of molecular signatures by
      searching the optima of a bi-objective function whose solution space was the set
      of all possible molecular signatures, ie, the set of subsets of genes. The two
      objectives were the size of the signature-to be minimized-and the interclass
      distance induced by the signature-to be maximized-. RESULTS: We showed that: 1)
      the convex combination of the two objectives had exactly n optimal non empty
      signatures where n was the number of genes, 2) the n optimal signatures were
      nested, and 3) the optimal signature of size k was the subset of k top ranked
      genes that contributed the most to the interclass distance. We applied our
      feature selection method on five public datasets in oncology, and assessed the
      prediction performances of the optimal signatures as input to the diagonal linear
      discriminant analysis (DLDA) classifier. They were at the same level or better
      than the best-reported ones. The predictions were robust, and the signatures were
      almost always significantly smaller. We studied in more details the performances
      of our predictive modeling on two breast cancer datasets to predict the response
      to a preoperative chemotherapy: the performances were higher than the previously
      reported ones, the signatures were three times smaller (11 versus 30 gene
      signatures), and the genes member of the signature were known to be involved in
      the response to chemotherapy. CONCLUSIONS: Defining molecular signatures as the
      optima of a bi-objective function that combined the signature size and the
      interclass distance was well founded and efficient for prediction in
      oncogenomics. The complexity of the computation was very low because the optimal
      signatures were the sets of genes in the ranking of their valuation. Software can
      be freely downloaded from http://gardeux-vincent.eu/DeltaRanking.php.

PMID- 25983541
TI  - Profiling age-related epigenetic markers of stomach adenocarcinoma in young and
      old subjects.
AB  - The purpose of our study is to identify epigenetic markers that are differently
      expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The
      Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in
      methylation patterns and changes in gene and miRNA expression levels in young (n
      = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and
      653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age
      related expression patterns and 113 differentially methylated genes (DMGs),
      respectively. Our further analysis revealed that significant upregulated genes (n
      = 35) were assigned to the cell cycle, while the muscle system process (n = 27)
      and cell adhesion-related genes (n = 57) were downregulated. In addition, by
      comparing gene and miRNA expression with methylation change, we identified that
      three upregulated genes (ELF3, IL1beta, and MMP13) known to be involved in
      inflammatory responses and cell growth were significantly hypomethylated in the
      promoter region. We further detected target candidates for age-related,
      downregulated miRNAs (hsa-mir-124-3, hsa-mir-204, and hsa-mir-125b-2) in old STAD
      subjects. This is the first report of the results from a study exploring age
      related epigenetic biomarkers of STAD using high-throughput data and provides
      evidence for a complex clinicopathological condition expressed by the age-related
      STAD progression. 

PMID- 25983542
TI  - Catchment area analysis using bayesian regression modeling.
AB  - A catchment area (CA) is the geographic area and population from which a cancer
      center draws patients. Defining a CA allows a cancer center to describe its
      primary patient population and assess how well it meets the needs of cancer
      patients within the CA. A CA definition is required for cancer centers applying
      for National Cancer Institute (NCI)-designated cancer center status. In this
      research, we constructed both diagnosis and diagnosis/treatment CAs for the
      Massey Cancer Center (MCC) at Virginia Commonwealth University. We constructed
      diagnosis CAs for all cancers based on Virginia state cancer registry data and
      Bayesian hierarchical logistic regression models. We constructed a
      diagnosis/treatment CA using billing data from MCC and a Bayesian hierarchical
      Poisson regression model. To define CAs, we used exceedance probabilities for
      county random effects to assess unusual spatial clustering of patients diagnosed
      or treated at MCC after adjusting for important demographic covariates. We used
      the MCC CAs to compare patient characteristics inside and outside the CAs. Among
      cancer patients living within the MCC CA, patients diagnosed at MCC were more
      likely to be minority, female, uninsured, or on Medicaid. 

PMID- 25983543
TI  - Selecting spatial scale of covariates in regression models of environmental
      exposures.
AB  - Environmental factors or socioeconomic status variables used in regression models
      to explain environmental chemical exposures or health outcomes are often in
      practice modeled at the same buffer distance or spatial scale. In this paper, we
      present four model selection algorithms that select the best spatial scale for
      each buffer-based or area-level covariate. Contamination of drinking water by
      nitrate is a growing problem in agricultural areas of the United States, as
      ingested nitrate can lead to the endogenous formation of N-nitroso compounds,
      which are potent carcinogens. We applied our methods to model nitrate levels in
      private wells in Iowa. We found that environmental variables were selected at
      different spatial scales and that a model allowing spatial scale to vary across
      covariates provided the best goodness of fit. Our methods can be applied to
      investigate the association between environmental risk factors available at
      multiple spatial scales or buffer distances and measures of disease, including
      cancers. 

PMID- 25983544
TI  - Generalized monotone incremental forward stagewise method for modeling count
      data: application predicting micronuclei frequency.
AB  - The cytokinesis-block micronucleus (CBMN) assay can be used to quantify
      micronucleus (MN) formation, the outcome measured being MN frequency. MN
      frequency has been shown to be both an accurate measure of chromosomal
      instability/DNA damage and a risk factor for cancer. Similarly, the Agilent 4*44k
      human oligonucleotide microarray can be used to quantify gene expression changes.
      Despite the existence of accepted methodologies to quantify both MN frequency and
      gene expression, very little is known about the association between the two. In
      modeling our count outcome (MN frequency) using gene expression levels from the
      high-throughput assay as our predictor variables, there are many more variables
      than observations. Hence, we extended the generalized monotone incremental
      forward stagewise method for predicting a count outcome for high-dimensional
      feature settings. 

PMID- 25983546
TI  - Evaluating geographically weighted regression models for environmental chemical
      risk analysis.
AB  - In the evaluation of cancer risk related to environmental chemical exposures, the
      effect of many correlated chemicals on disease is often of interest. The
      relationship between correlated environmental chemicals and health effects is not
      always constant across a study area, as exposure levels may change spatially due
      to various environmental factors. Geographically weighted regression (GWR) has
      been proposed to model spatially varying effects. However, concerns about
      collinearity effects, including regression coefficient sign reversal (ie,
      reversal paradox), may limit the applicability of GWR for environmental chemical
      risk analysis. A penalized version of GWR, the geographically weighted lasso, has
      been proposed to remediate the collinearity effects in GWR models. Our focus in
      this study was on assessing through a simulation study the ability of GWR and GWL
      to correctly identify spatially varying chemical effects for a mixture of
      correlated chemicals within a study area. Our results showed that GWR suffered
      from the reversal paradox, while GWL overpenalized the effects for the chemical
      most strongly related to the outcome. 

PMID- 25983545
TI  - Evaluation of the performance of smoothing functions in generalized additive
      models for spatial variation in disease.
AB  - Generalized additive models (GAMs) with bivariate smoothing functions have been
      applied to estimate spatial variation in risk for many types of cancers. Only a
      handful of studies have evaluated the performance of smoothing functions applied
      in GAMs with regard to different geographical areas of elevated risk and
      different risk levels. This study evaluates the ability of different smoothing
      functions to detect overall spatial variation of risk and elevated risk in
      diverse geographical areas at various risk levels using a simulation study. We
      created five scenarios with different true risk area shapes (circle, triangle,
      linear) in a square study region. We applied four different smoothing functions
      in the GAMs, including two types of thin plate regression splines (TPRS) and two
      versions of locally weighted scatterplot smoothing (loess). We tested the null
      hypothesis of constant risk and detected areas of elevated risk using analysis of
      deviance with permutation methods and assessed the performance of the smoothing
      methods based on the spatial detection rate, sensitivity, accuracy, precision,
      power, and false-positive rate. The results showed that all methods had a higher
      sensitivity and a consistently moderate-to-high accuracy rate when the true
      disease risk was higher. The models generally performed better in detecting
      elevated risk areas than detecting overall spatial variation. One of the loess
      methods had the highest precision in detecting overall spatial variation across
      scenarios and outperformed the other methods in detecting a linear elevated risk
      area. The TPRS methods outperformed loess in detecting elevated risk in two
      circular areas. 

PMID- 25983547
TI  - Prediction of early breast cancer metastasis from DNA microarray data using high
      dimensional cox regression models.
AB  - BACKGROUND: DNA microarray studies identified gene expression signatures
      predictive of metastatic relapse in early breast cancer. Standard feature
      selection procedures applied to reduce the set of predictive genes did not take
      into account the correlation between genes. In this paper, we studied the
      performances of three high-dimensional regression methods - CoxBoost, LASSO
      (Least Absolute Shrinkage and Selection Operator), and Elastic net - to identify
      prognostic signatures in patients with early breast cancer. METHODS: We analyzed
      three public retrospective datasets, including a total of 384 patients with
      axillary lymph node-negative breast cancer. The Amsterdam van't Veer's training
      set of 78 patients was used to determine the optimal gene sets and classifiers
      using sensitivity thresholds resulting in mis-classification of no more than 10%
      of the poor-prognosis group. To ensure the comparability between different
      methods, an automatic selection procedure was used to determine the number of
      genes included in each model. The van de Vijver's and Desmedt's datasets were
      used as validation sets to evaluate separately the prognostic performances of our
      classifiers. The results were compared to the original Amsterdam 70-gene
      classifier. RESULTS: The automatic selection procedure reduced the number of
      predictive genes up to a minimum of six genes. In the two validation sets, the
      three models (Elastic net, LASSO, and CoxBoost) led to the definition of genomic
      classifiers predicting the 5-year metastatic status with similar performances,
      with respective 59, 56, and 54% accuracy, 83, 75, and 83% sensitivity, and 53,
      52, and 48% specificity in the Desmedt's dataset. In comparison, the Amsterdam 70
      gene signature showed 45% accuracy, 97% sensitivity, and 34% specificity. The
      gene overlap and the classification concordance between the three classifiers
      were high. All the classifiers added significant prognostic information to that
      provided by the traditional prognostic factors and showed a very high overlap
      with respect to gene ontologies (GOs) associated with genes overexpressed in the
      predicted poor-prognosis vs. good-prognosis classes and centred on cell
      proliferation. Interestingly, all classifiers reported high sensitivity to
      predict the 4-year status of metastatic disease. CONCLUSIONS: High-dimensional
      regression methods are attractive in prognostic studies because finding a small
      subset of genes may facilitate the transfer to the clinic, and also because they
      strengthen the robustness of the model by limiting the selection of false
      positive predictive genes. With only six genes, the CoxBoost classifier predicted
      the 4-year status of metastatic disease with 93% sensitivity. Selecting a few
      genes related to ontologies other than cell proliferation might further improve
      the overall sensitivity performance.

PMID- 25983548
TI  - Identifying molecular features associated with psychoneurological symptoms in
      women with breast cancer using multivariate mixed models.
AB  - Breast cancer (BC) is the second most common cancer among women. Research shows
      many women with BC experience anxiety, depression, and stress (ADS). Epigenetics
      has recently emerged as a potential mechanism for the development of depression.1
      Although there are growing numbers of research studies indicating that epigenetic
      changes are associated with ADS, there is currently no evidence that this
      association is present in women with BC. The goal of this study was to identify
      high-throughput methylation sites (CpG sites) that are associated with three
      psychoneurological symptoms (ADS) in women with BC. Traditionally, univariate
      models have been used to examine the relationship between methylation sites and
      each psychoneurological symptom; nevertheless, ADS can be treated as a cluster of
      related symptoms and included together in a multivariate linear model. Hence, an
      overarching goal of this study is to compare and contrast univariate and
      multivariate models when identifying methylation sites associated with ADS in
      women with BC. When fitting separate linear regression models for each ADS scale,
      3 among 285,173 CpG sites tested were significantly associated with depression.
      Two significant CpG sites are located on their respective genes FAM101A and
      FOXJ1, and the third site cannot be mapped to any known gene at this time. In
      contrast, the multivariate models identified 8,535 ADS-related CpG sites. In
      conclusion, when analyzing correlated psychoneurological symptom outcomes,
      multivariate models are more powerful and thus are recommended. 

PMID- 25983549
TI  - Recent Enhancements to the Genetic Risk Prediction Model BRCAPRO.
AB  - BRCAPRO is a widely used model for genetic risk prediction of breast cancer. It
      is a function within the R package BayesMendel and is used to calculate the
      probabilities of being a carrier of a deleterious mutation in one or both of the
      BRCA genes, as well as the probability of being affected with breast and ovarian
      cancer within a defined time window. Both predictions are based on information
      contained in the counselee's family history of cancer. During the last decade,
      BRCAPRO has undergone several rounds of successive refinements: the current
      version is part of release 2.1 of BayesMendel. In this review, we showcase some
      of the most notable features of the software resulting from these recent changes.
      We provide examples highlighting each feature, using artificial pedigrees
      motivated by complex clinical examples. We illustrate how BRCAPRO is a
      comprehensive software for genetic risk prediction with many useful features that
      allow users the flexibility to incorporate varying amounts of available
      information. 

PMID- 25983550
TI  - The standardized histogram shift of t2 magnetic resonance image (MRI) signal
      intensities of nephroblastoma does not predict histopathological diagnostic
      information.
AB  - The objective of this study is to assess standardized histograms of signal
      intensities of T2-weighted magnetic resonance image (MRI) modality before and
      after preoperative chemotherapy for nephroblastoma (Wilms' tumor). All analyzed
      patients are enrolled in the International Society of Paediatric Oncology (SIOP)
      2001/GPOH trial.1 The question to be answered is whether the comparison of the
      histograms can add new knowledge by comparing them with the histology of the
      tumor after preoperative chemotherapy. Twenty-three unilateral nephroblastoma
      cases were analyzed. All patients were examined by MRI before and after
      preoperative chemotherapy treatment. T2 modalities of the MRIs were selected, and
      histogram changes were compared to histopathological data available after
      surgery. Of the 23 tumors, 22 decreased in volume following chemotherapy (median 
      57.99%; range 15.65 to -90.82%). The preliminary results suggest that
      standardized histograms of signal intensities of T2 MRI in nephroblastoma is not
      predicting histopathological diagnostic information and has no implications for
      the clinical assessment for further chemotherapy. 

PMID- 25983551
TI  - Polymorphism in variable number of tandem repeats of dopamine d4 gene is a
      genetic risk factor in attention deficit hyperactive egyptian children: pilot
      study.
AB  - INTRODUCTION: The variable number of tandem repeats (VNTR) of the dopamine
      receptor D4 (DRD4) gene among humans may elucidate individual differences in
      susceptibility to neuropsychiatric diseases. Dopamine dysfunction may be involved
      with Attention Deficit Hyperactivity Disorder (ADHD) symptoms. In this study, we
      report the association between the phenotype of ADHD, a condition characterized
      by inattentiveness, hyperactivity, and impulsiveness, and a 48-base pair VNTR in
      exon 3 of the DRD4 polymorphism. SUBJECTS AND METHODS: We used a case control
      approach conducted on 29 ADHD and 31 ethnically matched control Egyptian children
      (ages 6-12 years). Cases were assessed by a psychiatric semi-structured interview
      and the Conners' Parent Rating Scale. VNTR polymorphisms of the DRD4 gene were
      done by touchdown PCR program using exon 3-specific primers followed by agarose
      gel electrophoresis. RESULTS: We observed a significant association between the
      existence of D4.4 allele of DRD4 and ADHD (P, 0.002); 6.9% of cases showed a
      single D4.4 and 10.3% showed a double D4.4 as compared to controls in whom D4.4
      has never been detected. CONCLUSION: Children with smaller number of repeat
      alleles (two to four repeats) of the DRD4 gene have higher possibility to develop
      ADHD in Egyptian children.

PMID- 25983553
TI  - Cross-disciplinary detection and analysis of network motifs.
AB  - The detection of network motifs has recently become an important part of network
      analysis across all disciplines. In this work, we detected and analyzed network
      motifs from undirected and directed networks of several different disciplines,
      including biological network, social network, ecological network, as well as
      other networks such as airlines, power grid, and co-purchase of political books
      networks. Our analysis revealed that undirected networks are similar at the basic
      three and four nodes, while the analysis of directed networks revealed the
      distinction between networks of different disciplines. The study showed that
      larger motifs contained the three-node motif as a subgraph. Topological analysis
      revealed that similar networks have similar small motifs, but as the motif size
      increases, differences arise. Pearson correlation coefficient showed strong
      positive relationship between some undirected networks but inverse relationship
      between some directed networks. The study suggests that the three-node motif is a
      building block of larger motifs. It also suggests that undirected networks share
      similar low-level structures. Moreover, similar networks share similar small
      motifs, but larger motifs define the unique structure of individuals. Pearson
      correlation coefficient suggests that protein structure networks, dolphin social
      network, and co-authorships in network science belong to a superfamily. In
      addition, yeast protein-protein interaction network, primary school contact
      network, Zachary's karate club network, and co-purchase of political books
      network can be classified into a superfamily. 

PMID- 25983552
TI  - Endogenous repair signaling after brain injury and complementary bioengineering
      approaches to enhance neural regeneration.
AB  - Traumatic brain injury (TBI) affects 5.3 million Americans annually. Despite the
      many long-term deficits associated with TBI, there currently are no clinically
      available therapies that directly address the underlying pathologies contributing
      to these deficits. Preclinical studies have investigated various therapeutic
      approaches for TBI: two such approaches are stem cell transplantation and
      delivery of bioactive factors to mitigate the biochemical insult affiliated with
      TBI. However, success with either of these approaches has been limited largely
      due to the complexity of the injury microenvironment. As such, this review
      outlines the many factors of the injury microenvironment that mediate endogenous
      neural regeneration after TBI and the corresponding bioengineering approaches
      that harness these inherent signaling mechanisms to further amplify regenerative
      efforts. 

PMID- 25983556
TI  - Computational and in vitro Investigation of miRNA-Gene Regulations in
      Retinoblastoma Pathogenesis: miRNA Mimics Strategy.
AB  - PURPOSE: Retinoblastoma (RB), a primary pediatric intraocular tumor, arises from
      primitive retinal layers. Several novel molecular strategies are being developed
      for the clinical management of RB. miRNAs are known to regulate cancer-relevant
      biological processes. Here, the role of selected miRNAs, namely, miR-532-5p and
      miR-486-3p, has been analyzed for potential therapeutic targeting in RB. METHODS:
      A comprehensive bioinformatic analysis was performed to predict the
      posttranscriptional regulators (miRNAs) of the select panel of genes [Group 1:
      oncogenes (HMGA2, MYCN, SYK, FASN); Group 2: cancer stem cell markers (TACSTD,
      ABCG2, CD133, CD44, CD24) and Group 3: cell cycle regulatory proteins (p53,
      MDM2)] using Microcosm, DIANALAB, miRBase v 18, and REFSEQ database, and RNA
      hybrid. The expressions of five miRNAs, namely, miR-146b-5p, miR-532-5p, miR-142
      5p, miR-328, and miR-486-3p, were analyzed by qRT-PCR on primary RB tumor samples
      (n = 30; including 17 invasive RB tumors and 13 noninvasive RB tumors). Detailed
      complementary alignment between 5' seed sequence of differentially expressed
      miRNAs and the sequence of target genes was determined. Based on minimum energy
      level and piCTAR scores, the gene targets were selected. Functional roles of
      these miRNA clusters were studied by using mimics in cultured RB (Y79, Weri Rb-1)
      cells in vitro. The gene targets (SYK and FASN) of the studied miRNAs were
      confirmed by qRT-PCR and western blot analysis. Cell proliferation and apoptotic
      studies were performed. RESULTS: Nearly 1948 miRNAs were identified in the in
      silico analysis, From this list, only 9 upregulated miRNAs (miR-146b-5p, miR-305,
      miR-663b, miR-299, miR-532-5p, miR-892b, miR-501, miR-142-5p, and miR-513b) and
      10 downregulated miRNAs (miR-1254, miR-328, miR-133a, miR-1287, miR-1299, miR
      375, miR-486-3p, miR-720, miR-98, and miR-122*) were found to be common with the
      RB serum miRNA profile. Downregulation of five miRNAs (miR-146b-5p, miR-532-5p,
      miR-142-5p, miR-328, and miR-486-3p) was confirmed experimentally. Predicted
      common oncogene targets (SYK and FASN) of miR-486-3p and miR-532-5p were
      evaluated for their mRNA and protein expression in these miRNA mimic-treated RB
      cells. Experimental overexpression of these miRNAs mediated apoptotic cell death
      without significantly altering the cell cycle in RB cells. CONCLUSION: Key miRNAs
      in RB pathogenesis were identified by an in silico approach. Downregulation of
      miR-486-3p and miR-532-5p in primary retinoblastoma tissues implicates their role
      in tumorigenesis. Prognostic and therapeutic potential of these miRNA was
      established by the miRNA mimic strategy.

PMID- 25983554
TI  - Reverse enGENEering of Regulatory Networks from Big Data: A Roadmap for
      Biologists.
AB  - Omics technologies enable unbiased investigation of biological systems through
      massively parallel sequence acquisition or molecular measurements, bringing the
      life sciences into the era of Big Data. A central challenge posed by such omics
      datasets is how to transform these data into biological knowledge, for example,
      how to use these data to answer questions such as: Which functional pathways are
      involved in cell differentiation? Which genes should we target to stop cancer?
      Network analysis is a powerful and general approach to solve this problem
      consisting of two fundamental stages, network reconstruction, and network
      interrogation. Here we provide an overview of network analysis including a step
      by-step guide on how to perform and use this approach to investigate a biological
      question. In this guide, we also include the software packages that we and others
      employ for each of the steps of a network analysis workflow. 

PMID- 25983557
TI  - Some correlates of electronic health information management system success in
      nigerian teaching hospitals.
AB  - Nowadays, an electronic health information management system (EHIMS) is crucial
      for patient care in hospitals. This paper explores the aspects and elements that
      contribute to the success of EHIMS in Nigerian teaching hospitals. The study
      adopted a survey research design. The population of study comprised 442 health
      information management personnel in five teaching hospitals that had implemented
      EHIMS in Nigeria. A self-developed questionnaire was used as an instrument for
      data collection. The findings revealed that there is a positive, close
      relationship between all the identified factors and EHIMS's success: technical
      factors (r = 0.564, P < 0.05); social factors (r = 0.616, P < 0.05);
      organizational factors (r = 0.621, P < 0.05); financial factors (r = 0.705, P <
      0.05); and political factors (r = 0.589, P < 0.05). We conclude that
      consideration of all the identified factors was highly significant for the
      success of EHIMS in Nigerian teaching hospitals. 

PMID- 25983555
TI  - Metagenomics: tools and insights for analyzing next-generation sequencing data
      derived from biodiversity studies.
AB  - Advances in next-generation sequencing (NGS) have allowed significant
      breakthroughs in microbial ecology studies. This has led to the rapid expansion
      of research in the field and the establishment of "metagenomics", often defined
      as the analysis of DNA from microbial communities in environmental samples
      without prior need for culturing. Many metagenomics statistical/computational
      tools and databases have been developed in order to allow the exploitation of the
      huge influx of data. In this review article, we provide an overview of the
      sequencing technologies and how they are uniquely suited to various types of
      metagenomic studies. We focus on the currently available bioinformatics
      techniques, tools, and methodologies for performing each individual step of a
      typical metagenomic dataset analysis. We also provide future trends in the field
      with respect to tools and technologies currently under development. Moreover, we
      discuss data management, distribution, and integration tools that are capable of
      performing comparative metagenomic analyses of multiple datasets using well
      established databases, as well as commonly used annotation standards. 

PMID- 25983558
TI  - Combination of rotational atherothrombectomy and Paclitaxel-coated angioplasty
      for femoropopliteal occlusion.
AB  - OBJECTIVE: The rotational atherothrombectomy with Straub Rotarex((r)) is a safe
      and efficient treatment of acute/subactute vascular occlusions. The purpose of
      this study was to evaluate the benefit of paclitaxel-coated angioplasty after
      rotational atherothrombectomy over an observation period of six months. MATERIALS
      AND METHODS: Overall, 29 patients were treated with the Rotarex catheter in
      combination with paclitaxel-coated angioplasty. All patients had acute/subacute
      and chronic occlusions of the superficial femoral artery (SFA) and/or popliteal
      arteries. The ankle-brachial index (ABI) was detected before the intervention,
      after the procedure, and after six months. Also clinical examination and
      ultrasound scans were done in the observation period. RESULTS: There were no
      technical failures. The ABI shows a significant increase from 0.52 +/- 0.17 to
      0.91 +/- 0.25 in the follow-up. By ultrasound examination, there were found two
      (6.9%) restenoses during the follow-up. There was one dissection during the
      intervention (3.5%). CONCLUSION: The rotational atherothrombectomy in combination
      with paclitaxel-coated angioplasty might be an effective and safe method with a
      promising low rate of restenosis at six months.

PMID- 25983560
TI  - Implications of Gender Difference in Coronary Calcification as Assessed by CT
      Coronary Angiography.
AB  - BACKGROUND: Arterial calcium as measured by 64-slice computed tomography coronary
      angiography (64-CT) is a reliable predictor of cardiovascular disease risk. Lipid
      rich plaques with lower degrees of calcification may pose greater risk for
      adverse coronary events than more stabilized calcified plaques as a result of the
      increased risk of plaque rupture, migration, and subsequent acute coronary
      syndrome. We sought to examine coronary artery calcium scores as measured via 64
      CT to assess the extent of calcification and plaque distribution in women
      compared to men. METHODS: A total of 138 patients referred for 64-CT were
      evaluated. Computerized tomographic angiography was performed using the GE
      LightSpeed VCT. Subgroup analysis comparing male and female data (including
      demographic data) was performed. All major coronary arteries were analyzed for
      coronary stenosis/plaque characterization as well as total vessel calcium
      (Agatston) score quantification. Patient demographics and coronary risk factors
      were recorded. RESULTS: A total of 552 coronary arteries were evaluated in 138
      patients (85 men, 53 women). The average age for females was 64.4 +/- 10.8 years
      and for males 60.0 +/- 12.8 years. The only demographic/cardiovascular risk
      factor in which the difference between men and women was significant was smoking
      history, where 23.5% of men had a history of smoking while only 9.6% of females
      endorsed having a smoking history (P < 0.044). On comparison of all total vessel
      calcium scores, males had a higher total mean calcium score than females in each
      individual vessel. The results were as follows for males versus females,
      respectively: left main total vessel calcium score 46.49 versus 16.71 (P =
      0.167); left anterior descending 265.21 versus 109.6 (P < 0.003); left circumflex
      130.5 versus 39.7 (P < 0.004); and right coronary 213.5 versus 73.8 (P < 0.01).
      The odds of having a total calcium score >100 (versus not) was 3.62 times greater
      in males relative to females, given that all the other cardiovascular risk
      factors are adjusted for (95% confidence interval: 1.37-9.54). On average, men
      had an average of 2.1 +/- 1.5 epicardial vessels with a calcium score >=11
      compared to 1.3 +/- 1.4 for women (P < 0.005). CONCLUSION: There are clear
      differences between males and females regarding total vessel calcium scores and
      therefore risk of future adverse coronary events. Males tended to have higher
      average calcium scores in each coronary artery than females with a greater
      tendency to have multiple vessel involvement. Using this information, more large
      scale, randomized controlled studies should be performed to correlate differences
      in the extent of coronary calcification with the observed variance in clinical
      presentation during coronary events between males and females as a means to
      potentially establish gender-specific therapeutic regimens.

PMID- 25983561
TI  - Substrate Modification Is a Better Predictor of Catheter Ablation Success in
      Atrial Fibrillation Than Pulmonary Vein Isolation: An LGE-MRI Study.
AB  - OBJECTIVES: Outcomes of catheter ablation of atrial fibrillation (AF) vary
      widely. We used late-gadolinium enhancement MRI (LGE-MRI) to examine the
      relationship of ablation-induced scarring in the pulmonary vein (PV) region and
      overall atrium to evaluate the role of PV encirclement and substrate modification
      in predicting outcome of catheter ablation in AF. METHODS AND RESULTS: LGE-MRI
      was performed to quantify baseline atrial fibrosis, which was classified into
      four stages (stage I with fibrosis <10%, stage II with fibrosis 10-20%, stage III
      with fibrosis 20-30%, and stage IV with fibrosis >=30%). Patients then underwent
      ablation and repeat LGE-MRI at three months to assess for ablation-induced
      scarring. PVs were studied to evaluate for complete encirclement with scar. Image
      processing was used to overlay the scar onto baseline fibrosis to assess the
      overlap and calculate residual fibrosis. A total of 172 patients were included
      with an average baseline fibrosis of 14.6 +/- 8.4%. The average number of PVs
      encircled with scar at three months was 1.2 +/- 1.3 with only 9% of patients
      having all four PVs completely encircled. The average residual fibrosis was 11.9
      +/- 7.3%. High residual fibrosis was defined as >10%. Recurrent AF was found in
      60 patients (34.9%) over a follow-up of 346 +/- 82 days. Baseline and high
      residual fibrosis were significant predictors of recurrence (hazard ratio [HR] of
      2.2; P < 0.01 and HR of 3.2; P < 0.01, respectively). The number of PV encircled
      was not a significant predictor of recurrence. CONCLUSION: LGE-MRI of ablation
      induced scarring demonstrates that chronic PV encirclement is rarely achieved.
      Procedural outcomes are better predicted by baseline atrial fibrosis and ablation
      induced substrate modification.

PMID- 25983559
TI  - Sex differences in inflammation during atherosclerosis.
AB  - Atherosclerosis is the leading cause of death in the United States and worldwide,
      yet more men die from atherosclerosis than women, and at a younger age. Women, on
      the other hand, mainly develop atherosclerosis following menopause, and
      particularly if they have one or more autoimmune diseases, suggesting that the
      immune mechanisms that increase disease in men are different from those in women.
      The key processes in the pathogenesis of atherosclerosis are vascular
      inflammation, lipid accumulation, intimal thickening and fibrosis, remodeling,
      and plaque rupture or erosion leading to myocardial infarction and ischemia.
      Evidence indicates that sex hormones alter the immune response during
      atherosclerosis, resulting in different disease phenotypes according to sex.
      Women, for example, respond to infection and damage with increased antibody and
      autoantibody responses, while men have elevated innate immune activation. This
      review describes current knowledge regarding sex differences in the inflammatory
      immune response during atherosclerosis. Understanding sex differences is critical
      for improving individualized medicine. 

PMID- 25983562
TI  - Testosterone replacement and cardiovascular safety: no straight and narrow!
AB  - The past decade has seen a tremendous increase in the number of men treated for
      hypogonadism with the expectation of symptomatic benefit. However, the long-term
      cardiovascular safety of testosterone replacement remains unknown because
      retrospective studies of testosterone replacement have been inconsistent, and
      definitive, prospective, randomized studies are lacking. The purpose of this
      review is to critically appraise the studies on testosterone replacement and
      cardiovascular outcomes. 

PMID- 25983563
TI  - Percutaneous Ventricular Assist Devices and ECMO in the Management of Acute
      Decompensated Heart Failure.
AB  - The successful treatment of acute decompensated heart failure continues to evolve
      with an increasing utilization of nondurable mechanical support devices.
      Indications for acute support have broadened to include their use as a bridge to
      recovery or decision (for durable ventricular assist devices [VADs] or heart
      transplant). Available devices have improved in terms of effectiveness, ease of
      insertion, and reduction in complications. The commonly used devices (intra
      aortic balloon pump, TandemHeart, Impella, and extracorporeal membrane
      oxygenation circuit), together with their mechanisms of action, are reviewed.
      Current considerations for support, specific to each device, are examined and
      future directions and indications for percutaneous VADs are explored. 

PMID- 25983564
TI  - Mechanical Circulatory Support and the Role of LVADs in Heart Failure Therapy.
AB  - Heart failure is epidemic in the United States with a prevalence of over 5
      million. The diagnosis carries a mortality risk of 50% at 5 years rivaling many
      diagnoses of cancer. Heart transplantation, long the "gold standard" treatment
      for end stage heart failure unresponsive to maximal medical therapy falls way
      short of meeting the need with only about 2,000 transplants performed annually in
      the United States due to donor limitation. Left ventricular devices have emerged
      as a viable option for patients as both a "bridge to transplantation" and as a
      final "destination therapy". 

PMID- 25983565
TI  - A case of chronic neutrophilic leukemia successfully treated with pegylated
      interferon alpha-2a.
AB  - Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN)
      that represents a diagnostic dilemma for both clinicians and pathologists.
      Because this disease entity is very rare, and because its diagnosis is by
      exclusion, it is important for clinical hematologists and hematopathologists to
      be familiar with CNL when approaching patients with MPNs and persistent
      neutrophilia. A woman in her 40s who was incidentally found to have leukocytosis
      was referred to the hematology service at the National Center for Cancer Care and
      Research for evaluation. Complete blood count revealed hyperleukocytosis with
      predominant neutrophilia. Peripheral blood and flow cytometry did not show any
      evidence of lymphoproliferative disorder or myeloblasts. Bone marrow aspirate and
      biopsy revealed a hypercellular marrow with myeloid hyperplasia. Cytogenetics
      revealed normal karyotype. Tests for both Janus kinase mutation JAK2 V617F and
      rearrangement of the genes BCR-ABL1, platelet-derived growth factor receptor
      alpha (PDGFRalpha), PDGFRbeta, and fibroblast growth factor receptor-1 (FGFR1)
      were negative. Thereafter, the diagnosis of CNL was reached. She was treated with
      pegylated interferon alpha-2a, with very good hematological response. To the best
      of our knowledge, this is the first case of CNL reported among the Arab
      population. 

PMID- 25983566
TI  - Cervical osteomyelitis with thoracic myelitis and meningitis in a diabetic
      patient.
AB  - A 45-year-old man with a history of untreated diabetes mellitus had a persisting
      fever, back pain, and diarrhea. The primary care physician diagnosed the patient
      with the flu and gastroenteritis. The patient developed paraplegia for two weeks
      and was admitted to another hospital. The physician in this hospital suspected
      infectious meningitis and myelitis, and administered piperacillin and steroids
      without cerebrospinal fluid (CSF) examination. On referral to our hospital, he
      presented a high fever and complete paraplegia. The lumbar puncture revealed a
      yellowish CSF, polynucleosis, and hypoglycorrhachia. Bacteria were not detected
      on Gram's staining and were not confirmed by CSF culture. Magnetic resonance
      imaging (MRI) showed no thoracolumbar lesion and suggested a cervical epidural
      abscess without any spinal cord compression. He was diagnosed as having
      osteomyelitis with meningitis and thoracic myelitis. The infection subsided with
      broad-spectrum antibiotics. After two weeks, bilateral sensorimotor disturbances
      of the upper extremities appeared. MRI findings showed the epidural abscess
      compressing the cervical spinal cord. We performed debridement of the epidural
      abscess. The infection was clinically controlled by using another antibiotic. One
      month after the infection subsided, a 360 degrees  reconstruction was performed.
      In this case, the misdiagnosis and the absence of CSF examination and culture to
      detect the pathogenic bacteria at an earlier stage in the patient's disease
      course might have led to the exacerbation of the pathology. 

PMID- 25983567
TI  - Extrahepatic biliary obstruction: an unusual presentation of hepatic sarcoidosis.
AB  - We report this case of a 63-year-old woman who presented with progressive illness
      characterized by abdominal pain, weight loss, anorexia, generalized weakness, and
      fatigue. The patient was found to have obstructive jaundice with multiple mass
      lesions in the liver, spleen, and kidney on computed tomography scan of abdomen.
      She developed cholangitis, necessitating an emergent endoscopic retrograde
      cholangiopancreatography with biliary stenting and decompression. Later, she was
      found to have hepatic sarcoidosis on wedge biopsy of the liver. Extrinsic
      compression of biliary tree from mass effect of sarcoid granulomas with
      superimposed biliary sepsis is rare. 

PMID- 25983568
TI  - On the occurrence of Ctenocheles (Decapoda, Axiidea, Ctenochelidae) in the
      Bohemian Cretaceous Basin.
AB  - Because of close morphological affinities, fossil cheliped fragments of the ghost
      shrimp Ctenocheles (Decapoda, Axiidea, Ctenochelidae) can be easily misidentified
      as remains of different decapod crustacean taxa. Re-examination of the Cretaceous
      decapods deposited in the National Museum in Prague revealed that all supposed
      specimens of the lobster genus Oncopareia found in the Middle Coniacian
      calcareous claystones of the Brezno Formation, including one of the Fritsch's
      original specimens of Stenocheles parvulus, actually belong to Ctenocheles. This
      material together with newly collected specimens from the same locality, allowed
      for erection of a new species, Ctenocheles fritschi. Its major chela possesses a
      serrated ischium and ovoid, unarmed merus; therefore, it is considered a close
      relative of the extant C. collini and C. maorianus. Ctenocheles fritschi sp. nov.
      represents the first report on the occurrence of the genus from the Bohemian
      Cretaceous Basin. It is one of the oldest records of Ctenocheles and
      simultaneously one of the best preserved fossils of the genus reported to date.
      Confusing taxonomy of S. parvulus is reviewed and shortly discussed.

PMID- 25983569
TI  - Complexity, Natural Selection and the Evolution of Life and Humans.
AB  - In this paper, I discuss the concept of complexity. I show that the principle of
      natural selection as acting on complexity gives a solution to the problem of
      reconciling the seemingly contradictory notion of generally increasing complexity
      and the observation that most species don't follow such a trend. I suggest the
      process of evolution to be illustrated by means of a schematic diagram of
      complexity versus time, interpreted as a form of the Tree of Life. The suggested
      model implies that complexity is cumulatively increasing, giving evolution a
      direction, an arrow of time, thus also implying that the latest emerging species
      will be the one with the highest level of complexity. Since the human species is
      the last species evolved in the evolutionary process seen at large, this means
      that we are the species with the highest complexity. The model implies that the
      human species constitutes an integral part of organic evolution, yet rendering us
      the exclusive status as the species of the highest complexity.

PMID- 25983570
TI  - Effect of intensive exercise in early adult life on telomere length in later life
      in men.
AB  - A career as an elite-class male athlete seems to improve metabolic heath in later
      life and is also associated with longer life expectancy. Telomere length is a
      biomarker of biological cellular ageing and could thus predict morbidity and
      mortality. The main aim of this study was to assess the association between
      vigorous elite-class physical activity during young adulthood on later life
      leukocyte telomere length (LTL). The study participants consist of former male
      Finnish elite athletes (n = 392) and their age-matched controls (n = 207).
      Relative telomere length was determined from peripheral blood leukocytes by
      quantitative real-time polymerase chain reaction. Volume of leisure-time physical
      activity (LTPA) was self-reported and expressed in metabolic equivalent hours. No
      significant difference in mean age-adjusted LTL in late life (p = 0.845) was
      observed when comparing former male elite athletes and their age-matched
      controls. Current volume of LTPA had no marked influence on mean age-adjusted LTL
      (p for trend 0.788). LTL was inversely associated with age (p = 0.004).Our study
      findings suggest that a former elite athlete career is not associated with LTL
      later in life. Key pointsA career as an elite-class athlete is associated with
      improved metabolic health in late life and is associated with longer life
      expectancy.A career as an elite-class athlete during young adulthood was not
      associated with leukocyte telomere length in later life.Current volume of leisure
      time physical activity did not influence telomere length in later life. 

PMID- 25983571
TI  - Difference between adolescent and collegiate baseball pitchers in the kinematics
      and kinetics of the lower limbs and trunk during pitching motion.
AB  - The purpose of this study was to clarify the differences between adolescent and
      collegiate baseball pitchers in the kinematic and kinetic profiles of the trunk
      and lower limbs during the pitching motion. The subjects were thirty-two
      adolescent baseball pitchers aged 12-15 years (APG) and thirty collegiate
      baseball pitchers aged 18-22 years (CPG). Three-dimensional motion analysis with
      a comprehensive lower-extremity model was used to evaluate kinematic and kinetic
      parameters during baseball pitching. The ground reaction forces (GRFs) of the
      pivot and stride legs during pitching were determined using two multicomponent
      force plates. The joint torques of hip, knee, and ankle were calculated by the
      inverse-dynamics computation of musculoskeletal human models using motion-capture
      data. To eliminate any effect of variation in body size, kinetic and GRFs data
      were normalized by dividing them by body mass. The velocity of a pitched ball was
      significantly higher (p < 0.01) in CPG (35.2 +/- 1.9 m.s(-1)) than in the APG
      (30.7 +/- 2.7 m.s(-1)). Most kinematic parameters for the lower limbs were
      similar between the CPG and the APG. Maximum Fy (toward the throwing direction)
      on the pivot leg and Fy and resultant forces on the stride leg at ball release
      were significantly greater in the CPG than in the APG (p < 0.05). Hip and knee
      joint torques on the lower limbs were significantly greater in the CPG than in
      the APG (p < 0.05). The present study indicates that the kinematics of lower
      limbs during baseball pitching are similar between adolescent and collegiate
      pitchers, but the momentum of the lower limbs during pitching is lower in
      adolescent pitchers than in collegiate ones, even when the difference in body
      mass is considered. Key pointsCollegiate baseball pitchers can generate the hip
      and knee joint torques on the pivot leg for accelerating the body
      forward.Collegiate baseball pitchers can generate the hip and knee joint torques
      to control/stabilize the stride leg in order to increase momentum on the stride
      leg during the arm acceleration phase.The kinematics of the lower limbs during
      baseball pitching are similar between adolescent and collegiate pitchers, but the
      momentum of the lower limbs during pitching is lower in adolescent pitchers than
      in collegiate ones, even when the difference in body mass is
      considered.Adolescent baseball pitchers cannot generate the hip and knee joint
      torques in the pivot and stride leg for transfer of the energy of trunk and the
      arm. 

PMID- 25983572
TI  - Predicting vertical jump height from bar velocity.
AB  - The objective of the study was to assess the use of maximum (Vmax) and final
      propulsive phase (FPV) bar velocity to predict jump height in the weighted jump
      squat. FPV was defined as the velocity reached just before bar acceleration was
      lower than gravity (-9.81 m.s(-2)). Vertical jump height was calculated from the
      take-off velocity (Vtake-off) provided by a force platform. Thirty swimmers
      belonging to the National Slovenian swimming team performed a jump squat
      incremental loading test, lifting 25%, 50%, 75% and 100% of body weight in a
      Smith machine. Jump performance was simultaneously monitored using an AMTI
      portable force platform and a linear velocity transducer attached to the barbell.
      Simple linear regression was used to estimate jump height from the Vmax and FPV
      recorded by the linear velocity transducer. Vmax (y = 16.577x - 16.384) was able
      to explain 93% of jump height variance with a standard error of the estimate of
      1.47 cm. FPV (y = 12.828x - 6.504) was able to explain 91% of jump height
      variance with a standard error of the estimate of 1.66 cm. Despite that both
      variables resulted to be good predictors, heteroscedasticity in the differences
      between FPV and Vtake-off was observed (r(2) = 0.307), while the differences
      between Vmax and Vtake-off were homogenously distributed (r(2) = 0.071). These
      results suggest that Vmax is a valid tool for estimating vertical jump height in
      a loaded jump squat test performed in a Smith machine. Key pointsVertical jump
      height in the loaded jump squat can be estimated with acceptable precision from
      the maximum bar velocity recorded by a linear velocity transducer.The
      relationship between the point at which bar acceleration is less than -9.81 m.s(
      2) and the real take-off is affected by the velocity of movement.Mean propulsive
      velocity recorded by a linear velocity transducer does not appear to be optimal
      to monitor ballistic exercise performance. 

PMID- 25983573
TI  - Hydration and thermoregulation during a half-ironman performed in tropical
      climate.
AB  - The aim of this study was to compare the core temperature (TC) and markers of
      hydration status in athletes performing a half Ironman triathlon race in hot and
      humid conditions (27.2 +/- 0.5 degrees C, relative humidity was 80 +/- 2%).
      Before and immediately after the 2012 Guadeloupe half Ironman triathlon, body
      mass and urine osmolarity (mean +/- SD) were measured in 19 well-trained male
      triathletes. TC was measured before and after the race, and at each transition
      during the event, using an ingestible pill telemetry system. Ambient temperature
      and heart rate (HR) were measured throughout the race. Mean +/- SD performance
      time was 331 +/- 36 minutes and HR was 147 +/- 16 beats.min(-1). Wet bulb globe
      temperature (WBGT) averaged 25.4 +/- 1.0 degrees C and ocean temperature was 29.5
      degrees C. The average TC at the beginning of the race (TC1) was 37.1 +/- 0.7
      degrees C; it was 37.8 +/- 0.9 degrees C after swimming (TC2), 37.8 +/- 1.0
      degrees C after cycling (TC3), and (TC4) 38.4 +/- 0.7 degrees C after running.
      Body mass significantly declined during the race by 3.7 +/- 1.9 kg (4.8 +/- 2.4%;
      p < 0.05), whereas urine osmolarity significantly increased from 491.6 +/- 300.6
      to 557.9 +/- 207.9 mosm.L(-1) (p < 0.05). Changes in body mass were not related
      to finishing TC or urine osmolarity. Ad libitum fluid intake appears applicable
      to athletes acclimatized to tropical climate, when performing a half Ironman
      triathlon in a warm and humid environment. Key pointsAd libitum fluid intake
      appears applicable to athletes acclimatized to tropical climate when performing a
      half Ironman triathlon in a warm and humid environment.The final core temperature
      average was 38.8 +/- 0.7oC after the event in these triathletes and the athletes
      showed no evidence of heat illness while competing in a warm and humid
      environment.Core temperature was dependent on both activity and anthropometry. 

PMID- 25983574
TI  - Neuromuscular and blood lactate responses to squat power training with different
      rest intervals between sets.
AB  - Studies investigating the effect of rest interval length (RI) between sets on
      neuromuscular performance and metabolic response during power training are
      scarce. Therefore, the purpose of this study was to compare maximal power output,
      muscular activity and blood lactate concentration following 1, 2 or 3 minutes RI
      between sets during a squat power training protocol. Twelve resistance-trained
      men (22.7 +/- 3.2 years; 1.79 +/- 0.08 cm; 81.8 +/- 11.3 kg) performed 6 sets of
      6 repetitions of squat exercise at 60% of their 1 repetition maximum. Peak and
      average power were obtained for each repetition and set using a linear position
      transducer. Muscular activity and blood lactate were measured pre and post
      exercise session. There was no significant difference between RI on peak power
      and average power. However, peak power decreased 5.6%, 1.9%, and 5.9% after 6
      sets using 1, 2 and 3 minutes of RI, respectively. Average power also decreased
      10.5% (1 min), 2.6% (2 min), and 4.3% (3 min) after 6 sets. Blood lactate
      increased similarly during the three training sessions (1-min: 5.5 mMol, 2-min:
      4.3 mMol, and 3-min: 4.0 mMol) and no significant changes were observed in the
      muscle activity after multiple sets, independent of RI length (pooled ES for 1
      min: 0.47, 2-min: 0.65, and 3-min: 1.39). From a practical point of view, the
      results suggest that 1 to 2 minute of RI between sets during squat exercise may
      be sufficient to recover power output in a designed power training protocol.
      However, if training duration is malleable, we recommend 2 min of RI for optimal
      recovery and power output maintenance during the subsequent exercise sets. Key
      pointsThis study demonstrates that 1 minute of RI between sets is sufficient to
      maintain maximal power output during multiple sets of a power-based exercise when
      it is composed of few repetitions and the sets are not performed until failure.
      Therefore, a short RI should be considered when designing training programs for
      the development of muscular power.Short RI may be more practical for strength
      coaches under time constraints (i.e. 1 minute of RI required only 7 minutes to
      complete an exercise session, while with 2 minutes take 12 minutes, and 17
      minutes with 3 minutes of RI).Future research is needed to examine the
      longitudinal effects of interval rest in training programs designed for the
      development of muscular power. 

PMID- 25983575
TI  - Lower extremity biomechanical relationships with different speeds in traditional,
      minimalist, and barefoot footwear.
AB  - Minimalist running footwear has grown increasingly popular. Prior studies that
      have compared lower extremity biomechanics in minimalist running to traditional
      running conditions are largely limited to a single running velocity. This study
      compares the effects of running at various speeds on foot strike pattern, stride
      length, knee angles and ankle angles in traditional, barefoot, and minimalist
      running conditions. Twenty-six recreational runners (19-46 years of age) ran on a
      treadmill at a range of speeds (2.5-4.0 m.sec(-1)). Subjects ran with four
      different footwear conditions: personal, standard, and minimalist shoes and
      barefoot. 3D coordinates from video data were collected. The relationships
      between speed, knee and ankle angles at foot strike and toe-off, relative step
      length, and footwear conditions were evaluated by ANCOVA, with speed as the co
      variate. Distribution of non-rearfoot strike was compared across shod conditions
      with paired t-tests. Non-rearfoot strike distribution was not significantly
      affected by speed, but was different between shod conditions (p < 0.05). Footwear
      condition and speed significantly affected ankle angle at touchdown, independent
      of one another (F [3,71] = 10.28, p < 0.001), with barefoot and minimalist
      running exhibiting greater plantarflexion at foot strike. When controlling for
      foot strike style, barefoot and minimalist runners exhibited greater
      plantarflexion than other conditions (p < 0.05). Ankle angle at lift-off and
      relative step length exhibited a significant interaction between speed and shod
      condition. Knee angles had a significant relationship with speed, but not with
      footwear. There is a clear influence of footwear, but not speed, on foot strike
      pattern. Additionally, speed and footwear predict ankle angles (greater
      plantarflexion at foot strike) and may have implications for minimalist runners
      and their risk of injury. Long-term studies utilizing various speeds and
      habituation times are needed. Key pointsFoot strike style does not change with
      speed, but does change with shod condition, with minimalist shoes exhibiting an
      intermediate distribution of forefoot strikes between barefoot and traditional
      shoes.Plantarflexion at touchdown does change with speed and with shoe type, with
      barefoot and minimalist shoes exhibiting a greater plantarflexion angle than
      traditional running shoes.Knee angles change with speed in all shod conditions,
      but knee flexion at touchdown is not different between shod conditions.Relative
      step length changes with speed and shod condition, but there is an interaction
      between these variables such that step length increases more quickly in
      traditional shoes as speed increases. 

PMID- 25983576
TI  - Changes of gait parameters and lower limb dynamics in recreational runners with
      achilles tendinopathy.
AB  - This study aimed to clarify the mechanical gait changes caused by achilles
      tendinopathy by comparing gait parameters and changes in hip, knee, and ankle
      moments between an experimental group (EG) and a control group (CG). Twenty
      runners with achilles tendinopathy were included in the EG (male/female: 10/10,
      age: 27.00 +/- 4.63), and 20 CG (male/female: 10/10, age: 27.25 +/- 4.33)
      participants were recruited. Subjects walked a 13-m distance at their normal
      walking speed 5 times to obtain motion analysis and joint moment data. Gait
      parameter analysis showed significant differences in double-limb support (EG:
      22.65 +/- 4.26%, CG: 20.37 +/- 4.46%), step length (EG: 0.58 +/- 0.0 7m, CG: 0.64
      +/- 0.08 m), step width (EG: 0.16 +/- 0.04 m, CG: 0.14 +/- 0.05 m), stride time
      (EG: 1.09 +/- 0.10 second, CG: 1.05 +/- 0.08 second), and walking speed (EG:
      1.09+/-0.18 m.s(-1), CG: 1.23 +/- 0.17 m.s(-1)) between the 2 groups (p < 0.05).
      Significant differences were found in hip joint moment for initial contact, mid
      stance, terminal stance, and pre-swing phases; knee joint moment for initial
      contact and pre-swing phases; and ankle joint moment for pre-swing and terminal
      swing phases (p < 0.05). Gait parameters and hip, knee, and ankle moments were
      altered in runners with achilles tendinopathy. Thus, clinical features of gait
      changes should be understood for optimal treatment of achilles tendinopathy;
      further research is required in this field. Key pointsA reduction in gait
      parameters, namely, step length, stride length, and walking speed, and an
      increase in double-limb support occurs in runners with achilles tendinopathy.A
      reduction in the hip extension moment occurs during the initial contact, as well
      as a reduction in the knee flexion moment from the mid-stance to pre-swing
      phases, a continuous decrease in the knee flexion moment from the early stance
      phase, and a reduction in the extension moment during the terminal stance phase.A
      reduction in the ankle plantar flexion moment occurs from the mid-stance phase
      and that a reduction in the dorsiflexion moment occurs during the terminal swing
      phase. 

PMID- 25983577
TI  - Body weight independently affects articular cartilage catabolism.
AB  - Although obesity is associated with osteoarthritis, it is unclear whether body
      weight (BW) independently affects articular cartilage catabolism (i.e.,
      independent from physiological factors that also accompany obesity). The primary
      purpose of this study was to evaluate the independent effect of BW on articular
      cartilage catabolism associated with walking. A secondary purpose was to
      determine how decreased BW influenced cardiovascular response due to walking.
      Twelve able-bodied subjects walked for 30 minutes on a lower-body positive
      pressure treadmill during three sessions: control (unadjusted BW), +40%BW, and 
      40%BW. Serum cartilage oligomeric matrix protein (COMP) was measured immediately
      before (baseline) and after, and 15 and 30 minutes after the walk. Heart rate
      (HR) and rate of perceived exertion (RPE) were measured every three minutes
      during the walk. Relative to baseline, average serum COMP concentration was 13%
      and 5% greater immediately after and 15 minutes after the walk. Immediately after
      the walk, serum COMP concentration was 14% greater for the +40%BW session than
      for the -40%BW session. HR and RPE were greater for the +40%BW session than for
      the other two sessions, but did not differ between the control and -40%BW
      sessions. BW independently influences acute articular cartilage catabolism and
      cardiovascular response due to walking: as BW increases, so does acute articular
      cartilage catabolism and cardiovascular response. These results indicate that
      lower-body positive pressure walking may benefit certain individuals by reducing
      acute articular cartilage catabolism, due to walking, while maintaining
      cardiovascular response. Key pointsWalking for 30 minutes with adjustments in
      body weight (normal body weight, +40% and -40% body weight) significantly
      influences articular cartilage catabolism, measured via serum COMP
      concentration.Compared to baseline levels, walking with +40% body weight and
      normal body weight both elicited significant increases in articular cartilage
      catabolism, while walking with -40% body weight did not.Cardiovascular response
      (HR and RPE) was not significantly different during walking with normal body
      weight and when compared to walking with -40% body weight. 

PMID- 25983579
TI  - An approach to identifying the effect of technique asymmetries on body alignment
      in swimming exemplified by a case study of a breaststroke swimmer.
AB  - Despite the importance of maintaining good alignment to minimize resistive drag
      in swimming there is a paucity of literature relating to the effect of technique
      asymmetries on rotations of the body about a vertical axis (yaw). The purpose of
      this paper was to present an approach to analyzing the effect of technique
      asymmetries on rotations in swimming, exemplifying the process with a case study
      of a breaststroke swimmer. The kinematics and angular kinetics of an elite female
      international breaststroke swimmer performing a 'fatigue set' of four 100m swims
      were derived from digitized three-dimensional video data using a 13 segment body
      model. Personalised anthropometric data required to quantify accurately segment
      and whole body centres of mass and segmental angular momentum were obtained by
      the elliptical zone method. Five episodes of torques producing yaw occurred in
      the stroke cycle sampled for each 100m swim of this swimmer. These torques were
      linked to bilateral differences in upper limb kinematics during 1) out-sweep; 2)
      in-sweep; 3) upper limb recovery; and lower limb kinematics during 4) Lower limb
      recovery and 5) the kick. It has been shown that by quantifying whole body
      torques, in conjunction with the kinematic movement patterns, the effect of
      technique asymmetries on body alignment can be assessed. Assessment of individual
      swimmers in this manner provides a solid foundation for planning interventions in
      strength, flexibility, and technique to improve alignment and performance. Key
      pointsA unique (not been attempted previously) study of yaw in breaststroke
      swimming that yields new knowledge of how technique and strength asymmetries
      affects body alignment.Establishes an approach to investigation of yaw in
      swimming using 3D videography and inverse dynamics.Exemplifies the approach with
      a case study. The case study illustrated the potential of the approach to enable
      detailed assessment of yaw and to explain how the yaw is produced in terms of the
      asymmetries in speed and magnitude of the swimming actions.This procedure should
      be used to identify and quantify asymmetries that might impair performance. 

PMID- 25983578
TI  - Microcurrent electrical neuromuscular stimulation facilitates regeneration of
      injured skeletal muscle in mice.
AB  - Conservative therapies, mainly resting care for the damaged muscle, are generally
      used as a treatment for skeletal muscle injuries (such as muscle fragmentation).
      Several past studies reported that microcurrent electrical neuromuscular
      stimulation (MENS) facilitates a repair of injured soft tissues and shortens the
      recovery period. However, the effects of MENS on the regeneration in injured
      skeletal muscle are still unclear. The purpose of this study was to investigate
      the effect of MENS on the regenerative process of injured skeletal muscle and to
      elucidate whether satellite cells in injured skeletal muscle are activated by
      MENS by using animal models. Male C57BL/6J mice, aged 7 weeks old, were used (n =
      30). Mice were randomly divided into two groups: (1) cardiotoxin (CTX)-injected
      (CX, n = 15) and (2) CTX-injected with MENS treatment (MX, n=15) groups. CTX was
      injected into tibialis anterior muscle (TA) of mice in CX and MX groups to
      initiate the necrosis-regeneration cycle of the muscle. TA was dissected 1, 2,
      and 3 weeks after the injection. Muscle weight, muscle protein content, the mean
      cross-sectional areas of muscle fibers, the relative percentage of fibers having
      central nuclei, and the number of muscle satellite cells were evaluated. MENS
      facilitated the recovery of the muscle dry weight and protein content relative to
      body weight, and the mean cross-sectional areas of muscle fibers in CTX-induced
      injured TA muscle. The number of Pax7-positive muscle satellite cells was
      increased by MENS during the regenerating period. Decrease in the percentages of
      fibers with central nuclei after CTX-injection was facilitated by MENS. MENS may
      facilitate the regeneration of injured skeletal muscles by activating the
      regenerative potential of skeletal muscles. Key pointsMicrocurrent electrical
      neuromuscular stimulation (MENS) facilitated the recovery of the relative muscle
      dry weight, the relative muscle protein content, and the mean cross-sectional
      areas of muscle fibers of injured TA muscle in mice.The number of satellite cells
      was increased by MENS during the regenerating phase of injured skeletal
      muscle.Decrease in the percentages of fibers with central nuclei was facilitated
      by MENS.MENS may facilitate the regeneration of injured skeletal muscles. 

PMID- 25983580
TI  - Unilateral plantar flexors static-stretching effects on ipsilateral and
      contralateral jump measures.
AB  - The aim of this study was to evaluate the acute effects of unilateral ankle
      plantar flexors static-stretching (SS) on the passive range of movement (ROM) of
      the stretched limb, surface electromyography (sEMG) and single-leg bounce drop
      jump (SBDJ) performance measures of the ipsilateral stretched and contralateral
      non-stretched lower limbs. Seventeen young men (24 +/- 5 years) performed SBDJ
      before and after (stretched limb: immediately post-stretch, 10 and 20 minutes and
      non-stretched limb: immediately post-stretch) unilateral ankle plantar flexor SS
      (6 sets of 45s/15s, 70-90% point of discomfort). SBDJ performance measures
      included jump height, impulse, time to reach peak force, contact time as well as
      the sEMG integral (IEMG) and pre-activation (IEMGpre-activation) of the
      gastrocnemius lateralis. Ankle dorsiflexion passive ROM increased in the
      stretched limb after the SS (pre-test: 21 +/- 4 degrees  and post-test: 26.5 +/-
      5 degrees , p < 0.001). Post-stretching decreases were observed with peak force
      (p = 0.029), IEMG (P<0.001), and IEMGpre-activation (p = 0.015) in the stretched
      limb; as well as impulse (p = 0.03), and jump height (p = 0.032) in the non
      stretched limb. In conclusion, SS effectively increased passive ankle ROM of the
      stretched limb, and transiently (less than 10 minutes) decreased muscle peak
      force and pre-activation. The decrease of jump height and impulse for the non
      stretched limb suggests a SS-induced central nervous system inhibitory effect.
      Key pointsWhen considering whether or not to SS prior to athletic activities, one
      must consider the potential positive effects of increased ankle dorsiflexion
      motion with the potential deleterious effects of power and muscle activity during
      a simple jumping task or as part of the rehabilitation process.Since decreased
      jump performance measures can persist for 10 minutes in the stretched leg, the
      timing of SS prior to performance must be taken into consideration.Athletes,
      fitness enthusiasts and therapists should also keep in mind that SS one limb has
      generalized effects upon contralateral limbs as well. 

PMID- 25983581
TI  - Effects of time-release caffeine containing supplement on metabolic rate,
      glycerol concentration and performance.
AB  - This study compared caffeine pharmacokinetics, glycerol concentrations, metabolic
      rate, and performance measures following ingestion of a time-release caffeine
      containing supplement (TR-CAF) versus a regular caffeine capsule (CAF) and a
      placebo (PL). Following a double-blind, placebo-controlled, randomized, cross
      over design, ten males (25.9 +/- 3.2 y) who regularly consume caffeine ingested
      capsules containing either TR-CAF, CAF, or PL. Blood draws and performance
      measures occurred at every hour over an 8-hour period. Plasma caffeine
      concentrations were significantly greater (p < 0.05) in CAF compared to TR-CAF
      during hours 2-5 and significantly greater (p = 0.042) in TR-CAF compared to CAF
      at hour 8. There were no significant differences between trials in glycerol
      concentrations (p = 0.86) or metabolic measures (p = 0.17-0.91). Physical
      reaction time was significantly improved for CAF at hour 5 (p=0.01) compared to
      PL. Average upper body reaction time was significantly improved for CAF and TR
      CAF during hours 1-4 (p = 0.04 and p = 0.01, respectively) and over the 8-hour
      period (p = 0.04 and p = 0.001, respectively) compared to PL. Average upper body
      reaction time was also significantly improved for TR-CAF compared to PL during
      hours 5-8 (p = 0.004). TR-CAF and CAF showed distinct pharmacokinetics yielding
      modest effects on reaction time, yet did not alter glycerol concentration,
      metabolic measures, or other performance measures. Key pointsTime-release
      caffeine and regular caffeine showed distinct pharmacokinetics over an 8-hour
      period following ingestion.Time-release caffeine and regular caffeine yielded
      modest effects on reaction time over an 8-hour period following ingestion.Time
      release caffeine and regular caffeine did not alter glycerol concentration,
      metabolic measures, or other performance measures over an 8-hour period following
      ingestion. 

PMID- 25983582
TI  - Oxygen consumption of elite distance runners on an anti-gravity treadmill(r).
AB  - Lower body positive pressure (LBPP), or 'anti-gravity' treadmills(r) have become
      increasingly popular among elite distance runners. However, to date, few studies
      have assessed the effect of body weight support (BWS) on the metabolic cost of
      running among elite runners. This study evaluated how BWS influenced the
      relationship between velocity and metabolic cost among 6 elite male distance
      runners. Participants ran three- 16 minute tests consisting of 4 stages of 4
      minutes at 8, 7, 6 and 5 min.mile(-1) pace (3.35, 3.84, 4.47 and 5.36 m.s(-1)),
      while maintaining an aerobic effort (Respiratory Exchange Ratio <=1.00). One test
      was run on a regular treadmill, one on an anti-gravity treadmill with 40% BWS and
      one with 20% BWS being provided. Expired gas data were collected and regression
      equations used to determine and compare slopes. Significant decreases in oxygen
      uptake (VO2) were found with each increase in BWS (p < 0.001). At 20% BWS, the
      average decrease in net VO2 was greater than proportional (34%), while at 40%
      BWS, the average net reduction in VO2 was close to proportional (38%). Across
      velocities, the slope of the relationship between VO2 and velocity
      (DeltaVO2/Deltav) was steeper with less support. The slopes at both the 20% and
      40% BWS conditions were similar, especially when compared to the regular
      treadmill. Variability in VO2 between athletes was much greater on the LBPP
      treadmill and was greater with increased levels of BWS. In this study we
      evaluated the effect of body weight support on VO2 among elite distance runners.
      We have shown that oxygen uptake decreased with support, but not in direct
      proportion to that support. Further, because of the high variability in oxygen
      uptake between athletes on the LBPP treadmill, prediction equations may not be
      reliable and other indicators (heart rate, perceived exertion or directly
      measured oxygen uptake) should be used to guide training intensity when training
      on the LBPP treadmill. Key pointsWith increasing amounts of body weight-support
      (BWS), the slope of the relationship between velocity and oxygen consumption
      (DeltaVO2/Deltav) decreases significantly. This means the change in oxygen
      consumption (VO2) is significantly smaller over a given change in velocity at
      higher amounts of BWS.There is a non-linear decrease in VO2 with increasing BWS.
      As such, with each increment in the amount of BWS provided, the reduction in VO2
      becomes increasingly smaller.This paper provides first of its kind data on the
      effects of BWS on the cost of running among highly trained, elite runners. The
      outcomes of this study are in line with previous findings among non-elite
      runners. 

PMID- 25983583
TI  - The Situated Management of Safety during Risky Sport: Learning from Skydivers'
      Courses of Experience.
AB  - The aim of this study was to determine how risks associated with skydiving can be
      managed within acceptable limits. Using "Course-of-Action" theory described by
      Theureau, four experienced skydivers viewed recordings of their jumps, from
      preparation to landing, to elicit their perceptions of these experiences. The
      sequences dealing with safety concerns were then extracted. Data analysis
      revealed seven typical sequences of activity to manage safety, labeled "To check
      the material during preparation," "To feel prepared and safe for the jump as the
      plane gains altitude," "To use the time of freefall," "To deploy the parachute,"
      "To fly safely," "To ensure a safe landing" and "To organize the structured
      packing of the parachute." These results showed how the skydivers mitigated
      safety risks through a heightened awareness of critical elements in the unfolding
      jump activity and sequences of distributed and timed concerns and actions. The
      implications for accident analysis, prevention and education for training in
      risky sports activity are provided. Key pointsThe skydivers' activity could be
      broken down into seven safety sequences.Each safety sequence was defined by
      specific involvements and directions at the very moment of the
      situation.Skydivers' safety concerns are embedded in the succession of two types
      of temporal horizon organization: immediate and short-term. 

PMID- 25983584
TI  - Expression of Heat Shock Proteins (HSPs) in Aged Skeletal Muscles Depends on the
      Frequency and Duration of Exercise Training.
AB  - The skeletal muscle in aged rats adapts rapidly following a period of exercise.
      This adaptation includes structural remodeling and biochemical changes such as an
      up-regulation of antioxidant enzymes, content of stress and heat shock proteins
      (HSPs). However, the associated molecular mechanisms mediating different types of
      exercise training-induced adaptations are not yet completely understood.
      Therefore, the purpose of this study was to investigate the effects of duration
      and frequency exercise on the expression of HSPs, antioxidant enzymes, and
      mitogen-activated protein kinase (MAPKs) in the skeletal muscles of aged rats.
      Young (3-month-old) and aged (20-month-old) male Sprague-Dawley rats were
      randomly assigned to 6 groups and extensor digitorum longus (EDL; fast twitch
      muscle fiber) and soleus (SOL; slow twitch muscle fiber) skeletal muscles were
      collected immediately. The expression pattern of HSPs in skeletal muscles was
      decreased in old groups compared with young groups. Especially, HSPs showed lower
      expression in SOL than EDL muscle. Interestingly, HSPs in aged rats was increased
      significantly after S1 (single long-duration; 1*30 min, 5 days/week for 6 weeks)
      and M1 types (multiple short-duration; 3*10 min.day(-1), 5 days.week(-1) for 6
      weeks) than S2 (single long-duration; 1*30 min, 3 days/week for 6 weeks) and M2
      (multiple short-duration; 3*10 min.day(-1), 3 days.week(-1) for 6 weeks) types of
      exercise training. Also, superoxide dismutase (SODs) showed similar expression as
      HSP did. On the contrary, the p-ERK and p-JNK were down regulated. In addition, p
      p38 level in the SOL muscle was activated markedly in all exercise groups. These
      results demonstrate that increasing of HSP expression through duration and
      frequency exercise can lead to protection and training-induced adaptation against
      aging-induced structural weakness in skeletal muscles. Key pointsThe expression
      of heat shock proteins (HSPs) in aged rats was increased significantly after
      single long-duration (S1) and multiple short-duration (M1) types than S2 and M2
      types of exercise training in soleus (SOL) skeletal muscles.Superoxide dismutase
      (SODs) showed similar expression as HSPs did. On the contrary, the p-ERK and p
      JNK were down regulated. In addition, p-p38 level in the SOL muscle was activated
      markedly in all exercise groups.Induction of HSPs and SODs by high duration and
      frequency of exercise training such as S1 and M1 types with concomitant MAPKs
      pathway depending on the type of muscles.The frequency and duration of exercise
      training could affect the functional adaptation and protection against aging
      induced structural weakness of skeletal muscles through changing expression of
      related molecules. 

PMID- 25983585
TI  - Estimation of Center of Mass Trajectory using Wearable Sensors during Golf Swing.
AB  - This study suggests a wearable sensor technology to estimate center of mass (CoM)
      trajectory during a golf swing. Groups of 3, 4, and 18 participants were
      recruited, respectively, for the purpose of three validation studies. Study 1
      examined the accuracy of the system to estimate a 3D body segment angle compared
      to a camera-based motion analyzer (Vicon(r)). Study 2 assessed the accuracy of
      three simplified CoM trajectory models. Finally, Study 3 assessed the accuracy of
      the proposed CoM model during multiple golf swings. A relatively high agreement
      was observed between wearable sensors and the reference (Vicon(r)) for angle
      measurement (r > 0.99, random error <1.2 degrees  (1.5%) for anterior-posterior;
      <0.9 degrees  (2%) for medial-lateral; and <3.6 degrees  (2.5%) for internal
      external direction). The two-link model yielded a better agreement with the
      reference system compared to one-link model (r > 0.93 v. r = 0.52, respectively).
      On the same note, the proposed two-link model estimated CoM trajectory during
      golf swing with relatively good accuracy (r > 0.9, A-P random error <1cm (7.7%)
      and <2cm (10.4%) for M-L). The proposed system appears to accurately quantify the
      kinematics of CoM trajectory as a surrogate of dynamic postural control during an
      athlete's movement and its portability, makes it feasible to fit the competitive
      environment without restricting surface type. Key pointsThis study demonstrates
      that wearable technology based on inertial sensors are accurate to estimate
      center of mass trajectory in complex athletic task (e.g., golf swing)This study
      suggests that two-link model of human body provides optimum tradeoff between
      accuracy and minimum number of sensor module for estimation of center of mass
      trajectory in particular during fast movements.Wearable technologies based on
      inertial sensors are viable option for assessing dynamic postural control in
      complex task outside of gait laboratory and constraints of cameras, surface, and
      base of support. 

PMID- 25983586
TI  - Effects of dietary Acid load on exercise metabolism and anaerobic exercise
      performance.
AB  - Dietary acid load, quantified as the potential renal acid load (PRAL) of the
      diet, affects systemic pH and acid-base regulation. In a previous cross-sectional
      study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is
      associated with higher respiratory exchange ratio (RER) values during maximal
      exercise. The purpose of the present study was to confirm the previous findings
      with a short-term dietary intervention study. Additionally, we sought to
      determine if changes in PRAL affects submaximal exercise RER (as a reflection of
      substrate utilization) and anaerobic exercise performance. Subjects underwent a
      graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise
      performance test on two occasions, once after following a low-PRAL diet and on a
      separate occasion, after a high-PRAL diet. The diets were continued as long as
      needed to achieve an alkaline or acid fasted morning urine pH, respectively, with
      all being 4-9 days in duration. RER was measured during the GXT with indirect
      calorimetry. The anaerobic performance test was a running time-to-exhaustion test
      lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to
      the high-PRAL trial (1.10 +/- 0.02 vs. 1.20 +/- 0.05, p = 0.037). The low-PRAL
      diet also resulted in a 21% greater time to exhaustion during anaerobic exercise
      (2.56 +/- 0.36 vs. 2.11 +/- 0.31 sec, p = 0.044) and a strong tendency for lower
      RER values during submaximal exercise at 70% VO2max (0.88 +/- 0.02 vs. 0.96 +/-
      0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline
      promoting) diet resulted in lower RER values during maximal-intensity exercise.
      However, the low-PRAL diet also increased anaerobic exercise time to exhaustion
      and appears to have shifted submaximal exercise substrate utilization to favor
      lipid oxidation and spare carbohydrate, both of which would be considered
      favorable effects in the context of exercise performance. Key pointsShort-term (4
      9 days) changes in the acid or alkaline promoting qualities of the diet,
      quantified as potential renal acid load (PRAL), alter systemic pH, as evidenced
      in the present study by changes in fasted morning urine pH. Low-PRAL (alkaline
      promoting) diets are characterized by high intakes of vegetables and fruits with
      limited consumption of meats, cheeses, and grains while high-PRAL diets are
      characterized by the opposite dietary pattern.An alkaline promoting (low-PRAL)
      diet increases anaerobic exercise performance, as evidenced by greater time-to
      exhaustion during high-intensity treadmill running.Preliminary evidence suggests
      that an alkaline promoting (low-PRAL) diet increases lipid oxidation and may have
      a carbohydrate-sparing effect during submaximal endurance exercise, although
      further studies are needed.In contrast to what has been observed in response to
      habitual/long-term dietary patterns, a short-term low-PRAL diet does not increase
      maximal exercise respiratory exchange ratio and even appears to lower it. This
      suggests that short-term and long-term alterations in PRAL have different
      physiologic effects on this parameter. 

PMID- 25983587
TI  - Maximal Oxygen Uptake cannot be Determined in the Incremental Phase of The
      Lactate Minimum Test on a Cycle Ergometer.
AB  - The aim of this study was to investigate the maximal oxygen uptake (VO2MAX)
      determined using the incremental phase of the lactate minimum test (LM) on a
      cycle ergometer. Fifteen trained men were submitted to a graded exercise test
      (GXT) to evaluate the VO2MAX and LM. The total durations of the GXT and LM were
      11.2+/-1.8 minutes (CI95%:10.2-12.3 minutes) and 25.3+/-3.2 minutes (CI95%:23.5
      27.0), respectively. For the variables measured at exhaustion in both the GXT and
      LM, the oxygen uptake (54.6 +/- 8.1 ml.kg(-1).min(-1) vs 50.0 +/- 7.7 ml.kg(
      1).min(-1)), carbon dioxide production (66.1 +/- 7.5 ml.kg(-1).min(-1) vs 50.4 +/
      8.0 ml.kg(-1).min(-1)), ventilation (153.9 +/- 19.0 L.min(-1) vs 129.9 +/- 22.9
      L.min(-1)), respiratory exchange ratio (1.22 +/- 0.10 vs1.01 +/- 0.05), maximal
      power output achieved (331.6 +/- 45.8 W vs 242.4 +/- 41.0 W), heart rate (183.1
      +/- 6.9 bpm vs175.9 +/- 10.6 bpm) and lactate (10.5 +/- 2.3 mmol.L(-1) vs 6.6 +/-
      2.2 mmol.L(-1)) were statistically lower in the LM (p < 0.05). However, the
      values of rating of perceived exertion (17.6 +/- 2.5 for GXT and 17.2 +/- 2.3 for
      LM) did not differ (ES = 0.12 and CV = 7.8%). There was no good agreement between
      the values of the VO2MAX from the GXT and VO2PEAK from the LM, as evidenced in
      the Bland-Altman plot (4.7 ml.kg(-1).min(-1) and 0.34 L.min(-1) of mean
      differences, respectively), as well as the high values of the upper and lower
      limits of agreement. We conclude that the VO2PEAK values obtained in the
      incremental phase of the LM underestimate the VO2MAX. Key pointsThe VO2MAX is not
      attained during the incremental phase of the lactate minimum test;The
      physiological responses at exhaustion during LM are not similar to physiological
      responses measured during GXT;There is a weak agreement between the peak VO2
      measured at exhaustion during LM and the VO2MAX measured during GXT. 

PMID- 25983588
TI  - Efflux of creatine kinase from isolated soleus muscle depends on age, sex and
      type of exercise in mice.
AB  - Elevated plasma creatine kinase (CK) activity is often used as an indicator of
      exercise-induced muscle damage. Our aim was to study effects of contraction type,
      sex and age on CK efflux from isolated skeletal muscles of mice. The soleus
      muscle (SOL) of adult (7.5-month old) female C57BL/6J mice was subjected to
      either 100 passive stretches, isometric contractions or eccentric contractions,
      and muscle CK efflux was assessed after two-hour incubation in vitro. SOL of
      young (3-month old) male and female mice was studied after 100 eccentric
      contractions. For adult females, muscle CK efflux was larger (p < 0.05) after
      eccentric contractions than after incubation without exercise (698 +/- 344 vs.
      268 +/- 184 mU.h(-1), respectively), but smaller (p < 0.05) than for young
      females after the same type of exercise (1069 +/- 341 mU.h(-1)). Eccentric
      exercise-induced CK efflux was larger in muscles of young males compared to young
      females (2046 +/- 317 vs 1069 +/- 341 mU . h(-1), respectively, p < 0.001). Our
      results show that eccentric contractions induce a significant increase in muscle
      CK efflux immediately after exercise. Isolated muscle resistance to exercise
      induced CK efflux depends on age and sex of mice. Key pointsMuscle lengthening
      contractions induce the highest CK efflux in vitro compared with similar protocol
      of isometric contractions or passive stretches.Muscle CK efflux in vitro is
      applicable in studying changes of sarcolemma permeability/integrity, a proxy of
      muscle damage, in response to muscle contractile activity.Isolated muscle
      resistance to exercise-induced CK efflux is greater in female compared to male
      mice of young age and is further increased in adult female mice. 

PMID- 25983589
TI  - Individual versus Standardized Running Protocols in the Determination of VO2max.
AB  - The purpose of this study was to determine whether an individually designed
      incremental exercise protocol results in greater rates of oxygen uptake (VO2max)
      than standardized testing. Fourteen well-trained, male runners performed five
      incremental protocols in randomized order to measure their VO2max: i) an
      incremental test (INCS+I) with pre-defined increases in speed (2 min at 8.64
      km.h(-1), then a rise of 1.44 km.h(-1) every 30 s up to 14.4 km.h(-1)) and
      thereafter inclination (0.5 degrees  every 30 s); ii) an incremental test (INCI)
      at constant speed (14.4 km.h(-1)) and increasing inclination (2 degrees  every 2
      min from the initial 0 degrees ); iii) an incremental test (INCS) at constant
      inclination (0 degrees ) and increasing speed (0.5 km.h(-1) every 30 s from the
      initial 12.0 km.h(-1)); iv) a graded exercise protocol (GXP) at a 1 degrees 
      incline with increasing speed (initially 8.64 km.h(-1) + 1.44 km.h(-1) every 5
      min); v) an individual exercise protocol (INDXP) in which the runner chose the
      inclination and speed. VO2max was lowest (-4.2%) during the GXP (p = 0.01; d =
      0.06-0.61) compared to all other tests. The highest rating of perceived exertion,
      heart rate, ventilation and end-exercise blood lactate concentration were similar
      between the different protocols (p < 0.05). The time to exhaustion ranged from 7
      min 18 sec (INCS) to 25 min 30 sec (GXP) (p = 0.01).The VO2max attained by
      employing an individual treadmill protocol does not differ from the values
      derived from various standardized incremental protocols. Key pointsThe mean
      maximum oxygen uptake during the GXP was lower than for all other
      tests.Differences in the maximum rate of oxygen uptake between the various
      protocols exhibited considerable inter-individual variation.From the current
      findings, it can be concluded that well trained athletes are able to perform an
      individually designed treadmill running protocol. 

PMID- 25983590
TI  - Negative Associations between Perceived Training Load, Volume and Changes in
      Physical Fitness in Professional Soccer Players.
AB  - The purpose of this study was to examine the usefulness of the rating of
      perceived exertion training load for monitoring changes in several aerobic
      fitness and neuromuscular performance variables during 9 weeks of soccer training
      in young professional players. Nineteen male soccer players (20.2 +/- 1.9 years)
      belonging to the same reserve team of a Spanish La Liga Club participated in this
      study. Countermovement jump (CMJ), CMJ arm swing, single leg CMJ, a sprint
      running test (i.e., 5 m and 15 m times) and an aerobic fitness running test were
      performed at the start of the pre-season (Test 1) and 9 weeks later (Test 2).
      During 9 weeks, after each training session and match, players reported their
      rating of perceived exertion (RPE) separately for respiratory (RPEres) and leg
      musculature (RPEmus) effort. The training load (TL) was calculated by multiplying
      the RPE value by the duration in minutes of each training session or match.
      Accumulated RPEmus, and associated TL, as well as accumulated training volume
      were negatively correlated with the changes in most physical fitness attributes
      after 9 weeks of training (r = -0.51 to -0.64). Present results suggest that a
      high perception of leg muscular effort associated with training sessions and
      matches, as well as an excessive accumulation of training volume (time), can
      impair the improvement in several physical fitness variables believed to be
      relevant for on-field soccer performance. Therefore, the independent assessment
      of leg muscular effort to quantify TL can be an interesting additional monitoring
      measure in soccer training. Key pointsThe purpose of this study was to examine
      the usefulness of the perceived exertion-derived TL for monitoring changes in
      several aerobic fitness and neuromuscular parameters during 9 weeks of soccer
      training in young professional players.A high perception of leg muscular effort
      associated with training and matches, as well as an excessive accumulation of
      training volume (time), can impair several physical fitness factors believed to
      be relevant for on-field soccer performance.The independent assessment of
      muscular effort to quantify TL can be an interesting additional monitoring
      measure in soccer training. 

PMID- 25983591
TI  - Biomechanical analysis of abdominal injury in tennis serves. A case report.
AB  - The serve is an important stroke in any high level tennis game. A well-mastered
      serve is a substantial advantage for players. However, because of its
      repeatability and its intensity, this stroke is potentially deleterious for upper
      limbs, lower limbs and trunk. The trunk is a vital link in the production and
      transfer of energy from the lower limbs to the upper limbs; therefore, kinematic
      disorder could be a potential source of risk for trunk injury in tennis. This
      research studies the case of a professional tennis player who has suffered from a
      medical tear on the left rectus abdominis muscle after tennis serve. The goal of
      the study is to understand whether the injury could be explained by an
      inappropriate technique. For this purpose, we analyzed in three dimensions the
      kinematic and kinetic aspects of the serve. We also performed isokinetic tests of
      the player's knees. We then compared the player to five other professional
      players as reference. We observed a possible deficit of energy transfer because
      of an important anterior pelvis tilt. Some compensation made by the player during
      the serve could be a possible higher abdominal contraction and a larger shoulder
      external rotation. These particularities could induce an abdominal overwork that
      could explain the first injury and may provoke further injuries. Key pointsIn the
      proximal-distal sequence, energy is transmitted from lower limbs to upper limps
      via trunk.The 3D analysis tool is an indispensable test for an objective
      evaluation of the kinematic in the tennis serve.Multiple evaluations techniques
      are useful for fuller comprehension of the kinematics and contribute to the
      awareness of the player's staff concerning pathologies and performance. 

PMID- 25983592
TI  - Altitude Exposure at 1800 m Increases Haemoglobin Mass in Distance Runners.
AB  - The influence of low natural altitudes (< 2000 m) on erythropoietic adaptation is
      currently unclear, with current recommendations indicating that such low
      altitudes may be insufficient to stimulate significant increases in haemoglobin
      mass (Hbmass). As such, the purpose of this study was to determine the influence
      of 3 weeks of live high, train high exposure (LHTH) at low natural altitude (i.e.
      1800 m) on Hbmass, red blood cell count and iron profile. A total of 16 elite or
      well-trained runners were assigned into either a LHTH (n = 8) or CONTROL (n = 8)
      group. Venous blood samples were drawn prior to, at 2 weeks and at 3 weeks
      following exposure. Hbmass was measured in duplicate prior to exposure and at 2
      weeks and at 3 weeks following exposure via carbon monoxide rebreathing. The
      percentage change in Hbmass from baseline was significantly greater in LHTH, when
      compared with the CONTROL group at 2 (3.1% vs 0.4%; p = 0.01;) and 3 weeks (3.0%
      vs -1.1%; p < 0.02, respectively) following exposure. Haematocrit was greater in
      LHTH than CONTROL at 2 (p = 0.01) and 3 weeks (p = 0.04) following exposure. No
      significant interaction effect was observed for haemoglobin concentration (p =
      0.06), serum ferritin (p = 0.43), transferrin (p = 0.52) or reticulocyte
      percentage (p = 0.16). The results of this study indicate that three week of
      natural classic (i.e. LHTH) low altitude exposure (1800 m) results in a
      significant increase in Hbmass of elite distance runners, which is likely due to
      the continuous exposure to hypoxia. Key pointsTwo and three weeks of LHTH
      altitude exposure (1800 m) results in a significant increase in HbmassLHTH
      altitude exposure increased Hbmass by 3.1% after 2 weeks, and 3.0% after 3 weeks
      of exposureLHTH altitude exposure may be a practical method to increase Hbmass in
      well-trained athletes. 

PMID- 25983593
TI  - A longitudinal study investigating the stability of anthropometry and soccer
      specific endurance in pubertal high-level youth soccer players.
AB  - We investigated the evolution and stability of anthropometric and soccer-specific
      endurance characteristics of 42 high-level, pubertal soccer players with high,
      average and low yo-yo intermittent recovery test level 1 (YYIR1) baseline
      performances over two and four years. The rates of improvement were calculated
      for each performance group, and intra-class correlations were used to verify
      short- and long-term stability. The main finding was that after two and four
      years, the magnitudes of the differences at baseline were reduced, although
      players with high YYIR1 baseline performance still covered the largest distance
      (e.g., low from 703 m to 2126 m; high from 1503 m to 2434 m over four years).
      Furthermore, the YYIR1 showed a high stability over two years (ICC = 0.76) and a
      moderate stability over four years (ICC = 0.59), due to large intra-individual
      differences in YYIR1 performances over time. Anthropometric measures showed very
      high stability (ICCs between 0.94 to 0.97) over a two-year period, in comparison
      with a moderate stability (ICCs between 0.57 and 0.75) over four years. These
      results confirm the moderate-to-high stability of high-intensity running
      performance in young soccer players, and suggest that the longer the follow-up,
      the lower the ability to predict player's future potential in running
      performance. They also show that with growth and maturation, poor performers
      might only partially catch up their fitter counterparts between 12 and 16 years.
      Key pointsYoung, high-level soccer players with a relatively low intermittent
      endurance capacity are capable to catch up with their better performing peers
      after four years.Individual development and improvements of anthropometric and
      physical characteristics should be considered when evaluating young soccer
      players. 

PMID- 25983594
TI  - Intra and inter-rater reliability of screening for movement impairments: movement
      control tests from the foundation matrix.
AB  - Pre-season screening is well established within the sporting arena, and aims to
      enhance performance and reduce injury risk. With the increasing need to identify
      potential injury with greater accuracy, a new risk assessment process has been
      produced; The Performance Matrix (battery of movement control tests). As with any
      new method of objective testing, it is fundamental to establish whether the same
      results can be reproduced between examiners and by the same examiner on
      consecutive occasions. This study aimed to determine the intra-rater test re-test
      and inter-rater reliability of tests from a component of The Performance Matrix,
      The Foundation Matrix. Twenty participants were screened by two experienced
      musculoskeletal therapists using nine tests to assess the ability to control
      movement during specific tasks. Movement evaluation criteria for each test were
      rated as pass or fail. The therapists observed participants real-time and tests
      were recorded on video to enable repeated ratings four months later to examine
      intra-rater reliability (videos rated two weeks apart). Overall test percentage
      agreement was 87% for inter-rater reliability; 98% Rater 1, 94% Rater 2 for test
      re-test reliability; and 75% for real-time versus video. Intraclass-correlation
      coefficients (ICCs) were excellent between raters (0.81) and within raters (Rater
      1, 0.96; Rater 2, 0.88) but poor for real-time versus video (0.23). Reliability
      for individual components of each test was more variable: inter-rater, 68-100%;
      intra-rater, 88-100% Rater 1, 75-100% Rater 2; and real-time versus video 31
      100%. Cohen's Kappa values for inter-rater reliability were 0.0-1.0; intra-rater
      0.6-1.0 for Rater 1; -0.1-1.0 for Rater 2; and -0.1-1 for real-time versus video.
      It is concluded that both inter and intra-rater reliability of tests in The
      Foundation Matrix are acceptable when rated by experienced therapists.
      Recommendations are made for modifying some of the criteria to improve
      reliability where excellence was not reached. Key pointsThe movement control
      tests of The Foundation Matrix had acceptable reliability between raters and
      within raters on different daysAgreement between observations made on tests
      performed real-time and on video recordings was low, indicating poor validity of
      use of video recordingsSome movement evaluation criteria related to specific
      tests that did not achieve excellent agreement could be modified to improve
      reliability. 

PMID- 25983595
TI  - Reliability of Three-Dimensional Linear Kinematics and Kinetics of Swimming
      Derived from Digitized Video at 25 and 50 Hz with 10 and 5 Frame Extensions to
      the 4(th) Order Butterworth Smoothing Window.
AB  - The purpose of this study was to explore the reliability of estimating three
      dimensional (3D) linear kinematics and kinetics of a swimmer derived from
      digitized video and to assess the effect of framing rate and smoothing window
      size. A stroke cycle of two high-level front crawl swimmers and one high level
      backstroke swimmer was recorded by four underwater and two above water video
      cameras. One of the front crawl swimmers was recorded and digitized at 50 Hz with
      a window for smoothing by 4(th) order Butterworth digital filter extending 10
      frames beyond the start and finish of the stroke cycle, while the other front
      crawl and backstroke swimmer were recorded and digitized at 25 Hz with the window
      extending five frames beyond the start and finish of the stroke cycle. Each
      camera view of the stroke cycle was digitized five times yielding five
      independent 3D data sets from which whole body centre of mass (CM) component
      velocities and accelerations were derived together with wrist and ankle linear
      velocities. Coefficients of reliability ranging from r = 0.942 to r = 0.999
      indicated that both methods are sufficiently reliable to identify real
      differences in net force production during the pulls of the right and left hands.
      Reliability of digitizing was better for front crawl when digitizing at 50Hz with
      10 frames extension than at 25 Hz with 5 frames extension (p < 0.01) and better
      for backstroke than front crawl (p < 0.01). However, despite the extension and
      reflection of data, errors were larger in the first 15% of the stroke cycle than
      the period between 15 and 85% of the stroke cycle for CM velocity and
      acceleration and for foot speed (p < 0.01). Key pointsAn inverse dynamics based
      on 3D position data digitized from multiple camera views above and below the
      water surface is sufficiently reliable to yield insights regarding force
      production in swimming additional to those of other approaches.The ability to
      link the force profiles to swimming actions and technique is enhanced by having
      additional data such as wrist and foot velocities that can be obtained readily
      from the digitized data.Sampling at 25 Hz with at least 5 samples before and
      after the period of interest is required for reliable data when using a 4th Order
      Butterworth Digital Filter. 

PMID- 25983596
TI  - Evaluation of Electromyographic Frequency Domain Changes during a Three-Minute
      Maximal Effort Cycling Test.
AB  - To evaluate the time course of EMG frequency changes during a three-minute
      maximal effort cycling test (3MT) session and to examine which parameter between
      mean (MNF) and median (MDF) frequency is more suitable for evaluation of changes
      in neuromuscular function throughout a 3MT. Eighteen recreationally-active men
      volunteered to participate in this study. Maximum voluntary contraction (MVC) was
      measured using a dynamometer to determine maximal EMG frequency of the vastus
      lateralis (VL) of the kicking leg during isometric knee extension. A maximal
      oxygen consumption test (VO2peak) on a cycle ergometer was performed to establish
      the appropriate load profile for the 3MT which was completed after a period of at
      least 48 hours. MNF, MDF and power output (PO) values were measured at 10-second
      epochs throughout the duration of the 3MT. Repeated measures analysis of variance
      was used to compare the changes in EMG frequency, relative to maximal values from
      the MVC, and change in PO during the testing procedure. MNF, Root Mean Square
      (RMS), and PO significantly decreased during the 3MT, while MDF did not change
      significantly. Statistically, EMG frequency and PO decreased at first and
      remained constant in response to the 3MT, which may be reflective of differing
      patterns of muscle fiber type fatigue throughout the testing session. Due to
      decreased variability, changes in neuromuscular function during this protocol may
      be better evaluated using MNF than MDF. Key pointsEMG frequency decreased
      initially and remained constant in response to all-out cycling test.The change in
      EMG frequency and power output were similar during all-out cycling test.MNF may
      be better than MDF for neuromuscular function evaluation during all-out cycling
      test due to decreased variability. 

PMID- 25983597
TI  - Investigating the Effects of Knee Flexion during the Eccentric Heel-Drop
      Exercise.
AB  - This study aimed to characterise the biomechanics of the widely practiced
      eccentric heel-drop exercises used in the management of Achilles tendinosis.
      Specifically, the aim was to quantify changes in lower limb kinematics, muscle
      lengths and Achilles tendon force, when performing the exercise with a flexed
      knee instead of an extended knee. A musculoskeletal modelling approach was used
      to quantify any differences between these versions of the eccentric heel drop
      exercises used to treat Achilles tendinosis. 19 healthy volunteers provided a
      group from which optical motion, forceplate and plantar pressure data were
      recorded while performing both the extended and flexed knee eccentric heel-drop
      exercises over a wooden step when barefoot or wearing running shoes. This data
      was used as inputs into a scaled musculoskeletal model of the lower limb. Range
      of ankle motion was unaffected by knee flexion. However, knee flexion was found
      to significantly affect lower limb kinematics, inter-segmental loads and triceps
      muscle lengths. Peak Achilles load was not influenced despite significantly
      reduced peak ankle plantarflexion moments (p < 0.001). The combination of reduced
      triceps lengths and greater ankle dorsiflexion, coupled with reduced ankle
      plantarflexion moments were used to provide a basis for previously unexplained
      observations regarding the effect of knee flexion on the relative loading of the
      triceps muscles during the eccentric heel drop exercises. This finding questions
      the role of the flexed knee heel drop exercise when specifically treating
      Achilles tendinosis. Key pointsA more dorsiflexed ankle and a flexing knee are
      characteristics of performing the flexed knee heel-drop eccentric exercise.Peak
      ankle plantarflexion moments were reduced with knee flexion, but did not reduce
      peak Achilles tendon force.Kinematic changes at the knee and ankle affected the
      triceps muscle length and resulted in a reduction in the amount of Achilles
      tendon work performed.A version of the heel-drop exercise which reduces the
      muscle length change will also reduce the amount of tendon stretch, reducing the
      clinical efficacy of the exercise. 

PMID- 25983599
TI  - Somatosensory nerve function, measured by vibration thresholds in asymptomatic
      tennis players: a pilot study.

PMID- 25983598
TI  - Heart Rate Unreliability during Interval Training Recovery in Middle Distance
      Runners.
AB  - Heart rate (HR) was tested as a reliable index for recovery management during
      interval training (IT), considering its relationship with the several factors
      involved in respiratory, metabolic and cardiovascular homeostasis. Thirteen
      runners underwent two different IT sessions: at 80% and 120% of the second
      ventilatory threshold (VT2). Throughout both sessions HR, oxygen uptake (VO2),
      carbon dioxide production (VCO2) and pulmonary ventilation (VE), were measured by
      means of a portable gas analyzer. Carbon dioxide production excess (CO2excess),
      respiratory exchange ratio (RER), oxygen pulse (OP) and oxygen debt (O2debt) were
      also estimated. A significant increase in HR values (144 versus 150 beats.min(-1)
      between the first recovery and the last, p < 0.001) was observed at 80% of the
      VT2 speed. At the over-threshold intensity, HR rose from 159 to 168 beats.min(-1)
      from the first recovery to the last (p < 0.001). OP showed a declining trend from
      the first to the last recovery at 80% at the VT2 speed (18.3 versus 16.4
      mL.beats(-1), p < 0.05) and between the first and the last recovery in tests
      performed at 120% of the VT2 speed (17.8 versus 16.3 mL.beats(-1), p < 0.05). No
      change occurred in CO2excess, VO2, RER, VE and O2debt. On the basis of our
      research, the use of fixed HR as a reliable index of the established recovery is
      inaccurate and unfit for training. The phenomenon of cardiac drift to set the
      restart timing after the repetitions, i.e. by progressively increasing HR values,
      should be taken into account by coaches. Key pointsDuring an IT session, if
      recovery time after repetitions is fixed, HR supplies a different indication
      compared to all the respiratory parameters: HR indicates an incomplete recovery
      while the other parameters do not.The use of fixed HR values as a reliable index
      of the established recovery during IT is inaccurate and it may be the cause of
      under-training.To set the restart timing after repetitions the phenomenon of
      cardiac drift should be taken into account by coaches.HR drift during recoveries
      did not appear linked to the CO2excess. 

PMID- 25983600
TI  - Cardiac biomarkers and cycling race.

PMID- 25983601
TI  - Prevention of occupational Back Pain.
AB  - This paper reviews scientific research on occupational back pain and focuses on
      prevention of this problem. It discusses some of the challenges of translating
      the evidence of this multi-factorial condition into policy. Medical science is
      currently unable to clearly distinguish between back pain caused by work and that
      possibly due to other causes but which affects the individual's capacity to work.
      Back pain affects the vast majority of people at some point in their lives and is
      very costly to both the health care system and the industry. Evidence suggests
      that heavy lifting, driving, and vibration of the whole body are linked to
      occupational back pain. Once the risk factors for occupational back pain are
      identified, an otherwise chronic and disabling condition can be prevented in the
      majority of patients. As explained in this article, three levels of prevention
      for occupational back pain have been reported as effective. Failure to implement
      preventive measures may lead to a high incidence of occupational back pain. 

PMID- 25983602
TI  - Effect of adverse childhood experiences on physical health in adulthood: Results
      of a study conducted in Baghdad city.
AB  - BACKGROUND: Studies have revealed a powerful relationship between adverse
      childhood experiences (ACEs) and physical and mental health in adulthood.
      Literature documents the conversion of traumatic emotional experiences in
      childhood into organic disease later in life. OBJECTIVE: The aim was to estimate
      the effect of childhood experiences on the physical health of adults in Baghdad
      city. SUBJECTS AND METHODS: A cross-sectional study was conducted from January
      2013 to January 2014. The study sample was drawn from Baghdad city. Multistage
      sampling techniques were used in choosing 13 primary health care centers and
      eight colleges of three universities in Baghdad. In addition, teachers of seven
      primary schools and two secondary schools were chosen by a convenient method.
      Childhood experiences were measured by applying a modified standardized ACEs
      International Questionnaire form and with questions for bonding to family and
      parental monitoring. Physical health assessment was measured by a modified
      questionnaire derived from Health Appraisal Questionnaire of Centers for Disease
      Control and Prevention. The questionnaire includes questions on cerebrovascular
      diseases, diabetes mellitus, tumor, respiratory and gastrointestinal diseases.
      RESULTS: Logistic regression model showed that a higher level of bonding to
      family (fourth quartile) is expected to reduce the risk of chronic physical
      diseases by almost the half (odds ratio = 0.57) and exposure to a high level of
      household dysfunction and abuse (fourth quartile) is expected to increase the
      risk of chronic physical diseases by 81%. CONCLUSION: Childhood experiences play
      a major role in the determination of health outcomes in adulthood, and early
      prevention of ACEs. Encouraging strong family bonding can promote physical health
      in later life.

PMID- 25983603
TI  - Is it reliable to measure the forearm blood pressure in children?
AB  - BACKGROUND: When the upper arm (UA) is inaccessible or a standard-sized blood
      pressure (BP) cuff is unavailable, some healthcare workers use the forearm (FA)
      to measure BP with a mercury sphygmomanometer. OBJECTIVE: The objective was to
      determine the accuracy of BP measurement in the arm and FA. DESIGN: Prospective,
      randomized study. SETTING: Department of Pediatrics, JNMC, Sawangi (Meghe).
      PARTICIPANTS: A total of 72 children aged 5-15 years. MEASUREMENTS: Mercury and
      Automatic (OMRON Tokyo, 108-0075 Japan) BP measurements were recorded from the
      arm and FA at 2 min intervals. RESULTS: In our study, 72 children of both sexes
      were enrolled. The mean age of the children was 10.13 +/- 2.82 years, and 48%
      were females. Pearson's correlation coefficient between FA and UA systolic BP
      (SBP) measured by mercury was 0.782, and for diastolic BP (DBP) it was 0.824.
      Similarly, Pearson's correlation coefficient between FA and UA SBP measured with
      an automated device (OMRON) was 0.843, and for DBP it was 0.846. The average
      readings for the SBP and DBP were higher in the FA than in the UA by
      approximately 3 mmHg. There was a statistically significant difference in both
      SBP and DBP. CONCLUSIONS: The FA is an acceptable method of BP monitoring when
      the UA cannot be accessed. The pressure from FA is probably higher than it would
      be from UA.

PMID- 25983604
TI  - Nigella sativa: A potential natural protective agent against cardiac dysfunction
      in patients with type 2 diabetes mellitus.
AB  - OBJECTIVES: To study the effect of Nigella sativa supplementation on cardiac
      functions in Type 2 diabetic patients treated with oral hypoglycemic agents.
      BACKGROUND: Diabetes mellitus is associated with a high risk of cardiovascular
      morbidity and mortality. A number of reported beneficial effects of N. sativa on
      cardiovascular function were the inspiration for this study. MATERIALS AND
      METHODS: Sixty patients with uncontrolled diabetes (hemoglobin A1c [HbA1c] >7%)
      and with no known cardiovascular complications were recruited from the outpatient
      diabetes clinic. They were assigned, by convenience, to two groups; the control
      group received activated charcoal as placebo while the test group received 2
      g/day of powdered N. sativa for 1-year. All patients continued with their
      standard oral hypoglycemic agents. Echocardiography was used to evaluate the
      diastolic function, systolic function, and left ventricular mass (LVM) before the
      intervention and after 6 and 12 months of the treatment. RESULTS: HbA1c decreased
      significantly in the N. sativa group but did not change in the control group.
      Echocardiographic assessment in the control group showed impairment in diastolic
      function after 12 months, but there were no significant changes in fractional
      shortening (FS) or ejection fraction (EF). Furthermore, left ventricular (LV)
      dimensions at diastole and systole, LVM, and LVM index were significantly
      increased. In N. sativa group, no significant changes were found in diastolic
      function or LVM. LV dimension at systole was decreased while FS and EF were
      significantly increased after 6 and 12 months. CONCLUSION: N. sativa
      supplementation may protect the hearts of type 2 diabetic patients from diastolic
      dysfunction while improving LV systolic function.

PMID- 25983605
TI  - Clinical presentation and causes of the delayed diagnosis of breast cancer in
      patients with pregnancy associated breast cancer.
AB  - OBJECTIVE: The objective was to assess the clinical presentation, delay of
      diagnosis, and the causes of delay in the diagnosis of patients with pregnancy
      associated breast cancer (PABC) and patients with non-PABC. PATIENTS AND METHODS:
      This was a face-to-face interview with women who had histologically confirmed BC.
      All respondents were interviewed at our hospital. RESULTS: We interviewed 56
      patients, 36 with non-PABC and 20 with PABC. Of the 20 patients with PABC, BC was
      diagnosed in 12 (60%) during pregnancy and 8 (40%) during postpartum. 18 of the
      patients (90%) with PABC presented mainly with a mass 3 (15%) with pain and
      ulcer, 5 (25%) with skin redness and thickening, 6 (30%) with nipple retraction
      and 4 (20%) with discharge 12 (60%) patients with PABC had delayed diagnosis and
      8 (40%) of this delay was due to physicians' reassurance, and 2 (10%) because of
      fear of cancer. Similarly, 35 (97%) patients with non-PABC presented with breast
      mass, 3 (8.3%) with infrequent pain 4 (11.11%) with inflammation 2 (5.55%) with
      ulcer 2 (5.55%) with nipple discharge and4 (11.11%) with thickening of the skin
      compared with PABC patients. Only 4 (11.11%) in non-PABC had delayed diagnosis,
      and for half of them the delay was due to the fear of cancer. Two patients with
      PABC and non-PABC were afraid of cancer 16.66% and 5.55%, respectively. However,
      8 (60%) of patients with PABC had delayed diagnosis compared to 0% of patients
      with non-PABC. CONCLUSION: In this study, the majority of patients with PABC or
      non-PABC presented with a breast lump. Other symptoms were more common in
      patients with PABC than in patients with non-PABC. An increased awareness of
      clinicians may help reduce delay in the diagnosis of patients with PABC.

PMID- 25983606
TI  - Three years of antibacterial consumption in Indonesian Community Health Centers:
      The application of anatomical therapeutic chemical/defined daily doses and drug
      utilization 90% method to monitor antibacterial use.
AB  - CONTEXT: Irrational use of antibacterial drugs in Community Health-Care Centers
      (CHCs) may lead to increased resistance, morbidity, and mortality. AIMS: The aim
      of this study was to determine patterns of antibacterial use at CHCs in a
      district of Indonesia and use this as data for an antibiotic policy. SETTINGS AND
      DESIGN: The observational-descriptive study was conducted in a district of
      Indonesia to obtain antibacterial use from 2008 to 2010. SUBJECTS AND METHODS:
      The data obtained from the report on the use of medicines were classified and
      processed using the anatomical therapeutic chemical (ATC) and defined daily doses
      (DDD) method, with DDD/1000 patients as a unit measurement. The number of
      patients was obtained from attending patients in that research period. The most
      abundant antibacterial drugs use segment was identified by the drug utilization
      90% (DU90%) method. STATISTICAL ANALYSIS USED: Descriptive analysis were
      performed in this study. RESULTS: Fourteen kinds of antibacterial drugs were used
      in 61 CHCs. The total of antibacterial drug use during the period 2008-2010 was
      871.36 DDD/1000 patients/day. Declining antibacterial use was observed between
      2008 and 2010. Six kinds of antibacterial drugs were the most commonly used. The
      data show that the average use per visit was as high as 24.41 DDD. CONCLUSIONS:
      Amoxicillin, sulfamethoxazole and trimethoprim are antibacterials that have to be
      reconsidered by physicians for use in the Bandung CHC. The high use of
      antibacterial drugs, as described in the study, can be used as reference to
      develop an antimicrobial stewardship program and increase awareness of
      resistance, adverse drug reaction and drug interaction of antibacterial drugs.

PMID- 25983607
TI  - Family medicine training in Saudi Arabia: Are there any variations among
      different regions?
AB  - AIMS: The aim was to compare Eastern, Makkah, and Asir regions in term of
      residents' perception of the achievement of training objectives, and to assess
      various rotations based on residents' perception. SETTINGS AND DESIGN: This cross
      sectional study was done among family medicine residents in the Eastern, Makkah,
      and Asir regions. METHODOLOGY: A questionnaire was developed by the investigator
      and validated by two experts. All residents, except R1 residents, were included.
      All data were collected by the investigator by direct contact with the residents.
      STATISTICAL ANALYSIS USED: Cronbach's alpha, analysis of variance, t-test, and
      univariate regression model as appropriate, were used. RESULTS: Reliability of
      the questionnaire was found to be 75.4%. One hundred and seven (response rate:
      83.6%) residents completed the questionnaire. There were 51 (47.7%), 27 (25.2%),
      and 29 (27.1%) residents in the program in the Eastern region, Makkah, and Asir,
      respectively. The mean age was 29.1 +/- 2.5 years; half of the residents were
      male, most of (83.2%) were married, and more than half (54.2%) of had worked in
      primary health care before joining the program. Overall, 45% of the residents
      perceived that they had achieved the training objectives. The highest rotations
      as perceived by the residents were psychiatry and otolaryngology while the lowest
      were orthopedics and ophthalmology. There were significant differences among the
      study regions with regard to the rotations in family medicine, internal medicine,
      orthopedics, general surgery, and emergency medicine. CONCLUSIONS: Overall, a
      good percentage of the residents perceived that they had achieved the training
      objectives. The rotations differed in the studied regions. Psychiatry and
      otolaryngology had the highest percentage of family medicine residents who
      perceived that they had achieved the training objectives while lowest was in
      internal medicine and obstetrics and gynecology. The highest rotations as
      perceived by the family medicine residents were psychiatry and otolaryngology
      while lowest were orthopedics and ophthalmology. Sharing of experience and
      further studies are needed to improve the program rotations.

PMID- 25983608
TI  - Why medical students do not like to join rural health service? An exploratory
      study in India.
AB  - INTRODUCTION: Inadequate, inequitable distribution of the medical workforce
      remains a challenge across the globe, and India is no exception. Odisha, a state
      in India faces a major shortage of doctors particularly in rural and remote
      areas. In order to address this challenge, it is essential to understand medical
      students' career plans, specialization preferences, choices of job location and
      sector, and views on working in rural and remote areas. This study explored the
      immediate and long-term career plans of final year medical students, their
      intended practice locations and underlying reasons for the choices. METHODOLOGY:
      A cross-sectional survey was conducted in all the medical colleges (three
      government and three private) in the state of Odisha. Through the systematic
      sampling method, data were gathered from 390 final year students. A semi
      structured questionnaire was administered to the students and data were analyzed
      using SPSS version 20. RESULTS: Of the 390 students, 290 (74.35%) were from a
      government college. The most preferred immediate career goal was postgraduation
      studies (45.9% of students in government medical schools and 54% in private).
      About 17% of government students and 9% of private students showed willingness to
      work in rural areas, in the long run. Nearly 44.5% mentioned opportunities for
      career growth, followed by the possibilities for higher education (26.8%) as
      major the factors for preferring an urban posting. Similarly, higher pay scales,
      better working conditions were major factors for preferring the private sector.
      Most of the students maintained that good housing, better salaries, and adequate
      facilities at the workplace would attract more students toward rural service.
      CONCLUSION: Since public funded medical students are not motivated to serve in
      rural settings, increasing the number of places or establishing new medical
      institutions may not be an effective solution to the issue. Approaches such as
      extended clinical apprenticeship in rural health facilities, long-term community
      engagement during medical studentship could be considered.

PMID- 25983609
TI  - Medical grand rounds in Riyadh, Saudi Arabia: Current attitudes and barriers.
AB  - BACKGROUND: Medical grand rounds (MGRs) are considered key educational tools in
      most academic medical institutions. In this multi-center cross-sectional survey,
      we tried to determine the current attitudes of local medical practitioners to
      MGRs, as well as perceived barriers. METHODOLOGY: A total of 120 physicians from
      the National Guard Hospital, King Fahad Medical City, King Khalid University
      Hospital and King Faisal Specialist Hospital participated in the survey. The
      questionnaire consisted of statements on attitudes and perceived barriers against
      participating in MGRs, as well as participants' levels of agreement. RESULTS:
      Most participants attend MGRs regularly (94.2%), claiming that it is mandatory
      (88%). Participants also agreed that MGRs were important tools for continuing
      medical education (89.2%) and that they provided an opportunity to both present
      materials and interact with their colleagues in other divisions (86.7% and 81.6%,
      respectively). The vast majority of respondents agreed that "topic review/update"
      and "inviting guest speakers" were the two most preferred suggestions for
      improving MGRs (94.2% and 92.5%, respectively). Major barriers included
      constraints of time (43.3%) and topics that were not patient-related (40.8%).
      CONCLUSION: MGRs in the major Tertiary Hospitals in Riyadh are well attended, and
      the majority of the local practitioners believe in the positive effect of MGRs in
      delivering quality and up to date medical knowledge. Time and physician-specific
      issues were identified as major barriers that needed to be addressed in order to
      maximize participation of medical staff.

PMID- 25983610
TI  - Can the diagnostic delay of oral cancer by healthcare practitioners be prevented?
      Who should bear the blame of delay?

PMID- 25983611
TI  - Erratum: Brief Arabic tobacco craving questionnaire: An investigation into
      craving and heavy smoking in Saudi Arabian males: Erratum.
AB  - [This corrects the article on p. 8 in vol. 22, PMID: 25657605.]. 

PMID- 25983612
TI  - Strengthening patient-centred communication in rural Ugandan health centres: A
      theory-driven evaluation within a cluster randomized trial.
AB  - This article describes a theory-driven evaluation of one component of an
      intervention to improve the quality of health care at Ugandan public health
      centres. Patient-centred services have been advocated widely, but such approaches
      have received little attention in Africa. A cluster randomized trial is
      evaluating population-level outcomes of an intervention with multiple components,
      including 'patient-centred services.' A process evaluation was designed within
      this trial to articulate and evaluate the implementation and programme theories
      of the intervention. This article evaluates one hypothesized mechanism of change
      within the programme theory: the impact of the Patient Centred Services component
      on health-worker communication. The theory-driven approach extended to evaluation
      of the outcome measures. The study found that the proximal outcome of patient
      centred communication was rated 10 percent higher (p < 0.008) by care seekers
      consulting with the health workers who were at the intervention health centres
      compared with those at control health centres. This finding will strengthen
      interpretation of more distal trial outcomes.

PMID- 25983613
TI  - Genetic mapping of resistance to Fusarium oxysporum f. sp. tulipae in tulip.
AB  - Fusarium oxysporum is a major problem in the production of tulip bulbs. Breeding
      for resistant cultivars through a conventional approach is a slow process due to
      the long life cycle of tulip. Until now, marker-assisted selection (MAS) has been
      hampered by the large genome size and the absence of a genetic map. This study is
      aimed at construction of the first genetic map for tulip and at the
      identification of loci associated with resistance to F. oxysporum. A cross
      pollinated population of 125 individuals segregating for Fusarium resistance was
      obtained from Tulipa gesneriana "Kees Nelis" and T. fosteriana "Cantata."
      Fusarium resistance of the mapping population was evaluated through a soil
      infection test in two consecutive years, and a spot inoculation test in which a
      green fluorescent protein tagged Fusarium strain was used for inoculation. The
      genetic maps have been constructed for the parents separately. The genetic map of
      "Kees Nelis" comprised 342 markers on 27 linkage groups covering 1707 cM, while
      the map of "Cantata" comprised 300 markers on 21 linkage groups covering 1201 cM.
      Median distance between markers was 3.9 cM for "Kees Nelis" and 3.1 cM for
      "Cantata." Six putative quantitative trait loci (QTLs) for Fusarium resistance
      were identified, derived from both parents. QTL2, QTL3, and QTL6 were significant
      in all disease tests. For the flanking markers of the QTLs, phenotypic means of
      the two allelic groups, segregating from a parent for such a marker, were
      significantly different. These markers will be useful for the development of MAS
      in tulip breeding.

PMID- 25983614
TI  - Climate and taxonomy underlie different elemental concentrations and
      stoichiometries of forest species: the optimum "biogeochemical niche".
AB  - We previously hypothesised the existence of a "biogeochemical niche" occupied by
      each plant species. Different species should have a specific elemental
      composition, stoichiometry and allocation as a consequence of their particular
      metabolism, physiology and structure (morphology) linked to their optimal
      functioning under the environmental (abiotic and biotic) conditions where they
      have evolved. We tested this hypothesis using data from the Catalan Forestry
      Inventory that covers different forest groups growing under a large climatic
      gradient. Mediterranean species that occupy hotter-drier environments have lower
      leaf N, P and K concentrations than non-Mediterranean forest species. Within a
      determined climatic biome, different species competing in the same space have
      different elemental compositions and allocations linked to their taxonomical
      differences and their phenotypic plasticity. Gymnosperms have a proportionally
      higher elemental allocation to leaves than to wood, higher C concentrations, and
      lower N, P and K concentrations mainly in the stem and branches than angiosperms.
      The differences among species are linked to asymmetrical use of different
      elements, suggesting that the biogeochemical niche is a final expression and
      consequence of long-term species adaptation to particular abiotic factors,
      ecological role (stress tolerant, ruderal, competitor), different soil occupation
      and use of resources to avoid interspecific competition, and finally of a certain
      degree of flexibility to adapt to current environmental shifts.

PMID- 25983615
TI  - A Monte Carlo method to estimate the confidence intervals for the concentration
      index using aggregated population register data.
AB  - In this paper, we introduce several statistical methods to evaluate the
      uncertainty in the concentration index (C) for measuring socioeconomic equality
      in health and health care using aggregated total population register data. The C
      is a widely used index when measuring socioeconomic inequality, but previous
      studies have mainly focused on developing statistical inference for sampled data
      from population surveys. While data from large population-based or national
      registers provide complete coverage, registration comprises several sources of
      error. We simulate confidence intervals for the C with different Monte Carlo
      approaches, which take into account the nature of the population data. As an
      empirical example, we have an extensive dataset from the Finnish cause-of-death
      register on mortality amenable to health care interventions between 1996 and
      2008. Amenable mortality has been often used as a tool to capture the
      effectiveness of health care. Thus, inequality in amenable mortality provides
      evidence on weaknesses in health care performance between socioeconomic groups.
      Our study shows using several approaches with different parametric assumptions
      that previously introduced methods to estimate the uncertainty of the C for
      sampled data are too conservative for aggregated population register data.
      Consequently, we recommend that inequality indices based on the register data
      should be presented together with an approximation of the uncertainty and suggest
      using a simulation approach we propose. The approach can also be adapted to other
      measures of equality in health.

PMID- 25983616
TI  - Empowering citizens in international governance of nanotechnologies.
AB  - The international dialogue on responsible governance of nanotechnologies engages
      a wide range of actors with conflicting as well as common interests. It is also
      characterised by a lack of evidence-based data on uncertain risks of in
      particular engineered nanomaterials. The present paper aims at deepening
      understanding of the collective decision making context at international level
      using the grounded theory approach as proposed by Glaser and Strauss in "The
      Discovery of Grounded Theory" (1967). This starts by discussing relevant concepts
      from different fields including sociological and political studies of
      international relations as well as political philosophy and ethics. This analysis
      of current trends in international law making is taken as starting point for
      exploring the role that a software decision support tool could play in multi
      stakeholder global governance of nanotechnologies. These theoretical ideas are
      then compared with the current design of the SUN Decision Support System (SUNDS)
      under development in the European project on Sustainable Nanotechnologies (SUN,
      www.sun-fp7.eu). Through constant comparison, the ideas are also compared with
      requirements of different stakeholders as expressed during a user workshop. This
      allows for highlighting discussion points for further consideration.

PMID- 25983617
TI  - Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese
      osteogenesis imperfecta family.
AB  - Osteogenesis imperfecta (OI) is a family of genetic disorders associated with
      bone loss and fragility. Mutations associated with OI have been found in genes
      encoding the type I collagen chains. People with OI type I often produce
      insufficient alpha1-chain type I collagen because of frameshift, nonsense, or
      splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter
      and mother who had both experienced two bone fractures. Because skeletal
      fragility is predominantly inherited, we focused on identifying mutations in
      COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by
      genomic DNA sequencing in the mother and daughter, but not in their relatives.
      The identification of this mutation led to the conclusion that they were affected
      by mild OI type I. Open reading frame analysis indicated that this frameshift
      mutation would truncate alpha1-chain type I collagen at residue p263
      (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The
      clinical data were consistent with the patients' diagnosis of mild OI type I
      caused by haploinsufficiency of alpha1-chain type I collagen. Combined with
      previous reports, identification of the novel mutation COL1A1-c.700delG in these
      patients suggests that additional genetic and environmental factors may influence
      the severity of OI. 

PMID- 25983618
TI  - Ancestral association between HLA and HFE H63D and C282Y gene mutations from
      northwest Colombia.
AB  - A significant association between HFE gene mutations and the HLA-A*03-B*07 and
      HLA-A*29-B*44 haplotypes has been reported in the Spanish population. It has been
      proposed that these mutations are probably connected with Celtic and North
      African ancestry, respectively. We aimed to find the possible ancestral
      association between HLA alleles and haplotypes associated with the HFE gene
      (C282Y and H63D) mutations in 214 subjects from Antioquia, Colombia. These were
      18 individuals with presumed hereditary hemochromatosis ("HH") and 196 controls.
      The HLA-B*07 allele was in linkage disequilibrium (LD) with C282Y, while HLA
      A*23, A*29, HLA-B*44, and B*49 were in LD with H63D. Altogether, our results show
      that, although the H63D mutation is more common in the Antioquia population, it
      is not associated with any particular HLA haplotype, whereas the C282Y mutation
      is associated with HLA-A*03-B*07, this supporting a northern Spaniard ancestry. 

PMID- 25983619
TI  - Clinical and molecular characterization of a Brazilian cohort of campomelic
      dysplasia patients, and identification of seven new SOX9 mutations.
AB  - Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal
      abnormality belonging to the subgroup of bent bone dysplasias. In addition to
      bowed lower limbs, CD typically includes the following: disproportionate short
      stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club
      feet. Up to three quarters of 46, XY individuals may be sex-reversed.
      Radiological signs include scapular and pubic hypoplasia, narrow iliac wings,
      spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to
      heterozygous mutations in SOX9, a major regulator of chondrocytic development. We
      present a detailed clinical and molecular characterization of nine Brazilian CD
      patients. Infants were either stillborn (n = 2) or died shortly after birth and
      presented similar phenotypes. Sex-reversal was observed in one of three
      chromosomally male patients. Sequencing of SOX9 revealed new heterozygous
      mutations in seven individuals. Six patients had mutations that resulted in
      premature transcriptional termination, while one infant had a single-nucleotide
      substitution at the conserved splice-site acceptor of intron 1. No clear genotype
      phenotype correlations were observed. This study highlights the diversity of SOX9
      mutations leading to lethal CD, and expands the group of known genetic
      alterations associated with this skeletal dysplasia. 

PMID- 25983620
TI  - Clinical significance of miR-140-5p and miR-193b expression in patients with
      breast cancer and relationship to IGFBP5.
AB  - The functional role of IGFBP5 in breast cancer is complicated. Experimental and
      bioinformatics studies have shown that IGFBP5 is targeted by miR-140-5p and miR
      193b, although this has not yet been proven in clinical samples. The aim of this
      study was to evaluate the expression of miR-140-5p and miR-193b in breast cancer
      and adjacent normal tissue and assess its correlation with IGFBP5 and the
      clinicopathological characteristics of the tumors. IGFBP5 protein expression was
      analyzed immunohistochemically and IGFBP5, miR-140 and miR-193b mRNA expression
      levels were analyzed with real-time RT-PCR. Tumor tissue had higher miR-140-5p
      expression than adjacent normal tissue (p = 0.015). Samples with no
      immunohistochemical staining for IGFBP5 showed increased miR-140-5p expression (p
      = 0.009). miR-140-5p expression was elevated in invasive ductal carcinomas (p =
      0.002), whereas basal-like tumors had decreased expression of miR-140-5p compared
      to other tumors (p = 0.008). Lymph node-positive samples showed an approximately
      13-fold increase in miR-140-5p expression compared to lymph node-negative tissue
      (p = 0.049). These findings suggest that miR-140-5p, but not miR-193b, could be
      an important determinant of IGFBP5 expression and clinical phenotype in breast
      cancer patients. Further studies are needed to clarify the expressional
      regulation of IGFBP5 by miR-140-5p. 

PMID- 25983621
TI  - Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with
      Cerebrotendinous Xanthomatosis.
AB  - Cerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by
      recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1),
      producing an alteration of the synthesis of bile acids, with an accumulation of
      cholestanol. Clinical characteristics include juvenile cataracts, diarrhea,
      tendon xanthomas, cognitive impairment and other neurological manifestations.
      Early diagnosis is critical, because treatment with chenodeoxycholic acid may
      prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX
      patients by sequencing its nine exons, exon-intron boundaries, and cDNA from
      peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the
      novel substitution c.256-1G > T that causes exon 2 skipping, leading to a
      premature stop codon in exon 3, and for the previously-known pathogenic mutation
      c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185
      1G > A that causes exon 7 skipping and the generation of a premature stop codon
      in exon 8, leading to the loss of the crucial adrenoxin binding domain of
      CYP27A1. 

PMID- 25983622
TI  - A novel c.1037C > G (p.Ala346Gly) mutation in TP63 as cause of the ectrodactyly
      ectodermal dysplasia and cleft lip/palate (EEC) syndrome.
AB  - Ectrodactyly - ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM
      604292) is a rare disorder determined by mutations in the TP63 gene. Most cases
      of EEC syndrome are associated to mutations in the DNA binding domain (DBD)
      region of the p63 protein. Here we report on a three-generation Brazilian family
      with three individuals (mother, son and grandfather) affected by EEC syndrome,
      determined by a novel mutation c.1037C > G (p.Ala346Gly). The disorder in this
      family exhibits a broad spectrum of phenotypes: two individuals were personally
      examined, one presenting the complete constellation of EEC syndrome
      manifestations and the other presenting an intermediate phenotype; the third
      affected, a deceased individual not examined personally and referred to by his
      daughter, exhibited only the split-hand/foot malformation (SHFM). Our findings
      contribute to elucidate the complex phenotype-genotype correlations in EEC
      syndrome and other related TP63-mutation syndromes. The possibility of the
      mutation c.1037C > G being related both to acro-dermato-ungual-lacrimal-tooth
      (ADULT) syndrome and SHFM is also raised by the findings here reported. 

PMID- 25983623
TI  - Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants
      with non-obstructive male infertility in a Polish population.
AB  - Spermatogenesis is a process where an important contribution of genes involved in
      folate-mediated one-carbon metabolism is observed. The aim of the present study
      was to investigate the association between male infertility and the MTHFR (677C >
      T; 1298A > C), MTR (2756A > G) and MTRR (66A > G) polymorphisms in a Polish
      population. No significant differences in genotype or allele frequencies were
      detected between the groups of 284 infertile men and of 352 fertile controls.
      These results demonstrate that common polymorphisms in folate pathway genes are
      not major risk factors for non-obstructive male infertility in the Polish
      population. 

PMID- 25983624
TI  - Genetic characterization of Uruguayan Pampa Rocha pigs with microsatellite
      markers.
AB  - In this study, we genetically characterized the Uruguayan pig breed Pampa Rocha.
      Genetic variability was assessed by analyzing a panel of 25 microsatellite
      markers from a sample of 39 individuals. Pampa Rocha pigs showed high genetic
      variability with observed and expected heterozygosities of 0.583 and 0.603,
      respectively. The mean number of alleles was 5.72. Twenty-four markers were
      polymorphic, with 95.8% of them in Hardy Weinberg equilibrium. The level of
      endogamy was low (FIS = 0.0475). A factorial analysis of correspondence was used
      to assess the genetic differences between Pampa Rocha and other pig breeds;
      genetic distances were calculated, and a tree was designed to reflect the
      distance matrix. Individuals were also allocated into clusters. This analysis
      showed that the Pampa Rocha breed was separated from the other breeds along the
      first and second axes. The neighbour-joining tree generated by the genetic
      distances DA showed clustering of Pampa Rocha with the Meishan breed. The
      allocation of individuals to clusters showed a clear separation of Pampa Rocha
      pigs. These results provide insights into the genetic variability of Pampa Rocha
      pigs and indicate that this breed is a well-defined genetic entity. 

PMID- 25983625
TI  - Chromosomal localization of microsatellite loci in Drosophila mediopunctata.
AB  - Drosophila mediopunctata has been used as a model organism for genetics and
      evolutionary studies in the last three decades. A linkage map with 48
      microsatellite loci recently published for this species showed five syntenic
      groups, which had their homology determined to Drosophila melanogaster
      chromosomes. Then, by inference, each of the groups was associated with one of
      the five major chromosomes of D. mediopunctata. Our objective was to carry out a
      genetic (chromosomal) analysis to increase the number of available loci with
      known chromosomal location. We made a simultaneous analysis of visible mutant
      phenotypes and microsatellite genotypes in a backcross of a standard strain and a
      mutant strain, which had each major autosome marked. Hence, we could establish
      the chromosomal location of seventeen loci; including one from each of the five
      major linkage groups previously published, and twelve new loci. Our results were
      congruent with the previous location and they open new possibilities to future
      work integrating microsatellites, chromosomal inversions, and genetic
      determinants of physiological and morphological variation. 

PMID- 25983626
TI  - Conservation implications of the mating system of the Pampa Hermosa landrace of
      peach palm analyzed with microsatellite markers.
AB  - Peach palm (Bactris gasipaes) is cultivated by many indigenous and traditional
      communities from Amazonia to Central America for its edible fruits, and is
      currently important for its heart-of-palm. The objective of this study was to
      investigate the mating system of peach palm, as this is important for
      conservation and breeding. Eight microsatellite loci were used to genotype 24
      open-pollinated progenies from three populations of the Pampa Hermosa landrace
      maintained in a progeny trial for genetic improvement. Both the multi-locus
      outcrossing rates (0.95 to 0.99) and the progeny level multi-locus outcrossing
      rates (0.9 to 1.0) were high, indicating that peach palm is predominantly
      allogamous. The outcrossing rates among relatives were significantly different
      from zero (0.101 to 0.202), providing evidence for considerable biparental
      inbreeding within populations, probably due to farmers planting seeds of a small
      number of open-pollinated progenies in the same plot. The correlations of
      paternity estimates were low (0.051 to 0.112), suggesting a large number of
      pollen sources (9 to 20) participating in pollination of individual fruit
      bunches. Effective population size estimates suggest that current germplasm
      collections are insufficient for long-term ex situ conservation. As with most
      underutilized crops, on farm conservation is the most important component of an
      integrated conservation strategy. 

PMID- 25983627
TI  - Developing a common bean core collection suitable for association mapping
      studies.
AB  - Because of the continuous introduction of germplasm from abroad, some collections
      have a high number of accessions, making it difficult to explore the genetic
      variability present in a germplasm bank for conservation and breeding purposes.
      Therefore, the aim of this study was to quantify and analyze the structure of
      genetic variability among 500 common bean accessions to construct a core
      collection. A total of 58 SSRs were used for this purpose. The polymorphism
      information content (PIC) in the 180 common bean accessions selected to compose
      the core collection ranged from 0.17 to 0.86, and the discriminatory power (DP)
      ranged from 0.21 to 0.90. The 500 accessions were clustered into 15 distinct
      groups and the 180 accessions into four distinct groups in the Structure
      analysis. According to analysis of molecular variance, the most divergent
      accessions comprised 97.2% of the observed genetic variability present within the
      base collection, confirming the efficiency of the selection criterion. The 180
      selected accessions will be used for association mapping in future studies and
      could be potentially used by breeders to direct new crosses and generate elite
      cultivars that meet current and future global market needs. 

PMID- 25983628
TI  - Characterization and expression analysis of WOX2 homeodomain transcription factor
      in Aegilops tauschii.
AB  - The WUSCHEL (WUS)-related homeobox (WOX) gene family coordinates transcription
      during the early phases of embryogenesis. In this study, a putative WOX2 homolog
      was isolated and characterized from Aegilops tauschii, the donor of D genome of
      Triticum aestivum. The sequence consisted of 2045 bp, and contained an open
      reading frame (ORF), encoded 322 amino acids. The predicted protein sequence
      contained a highly conserved homeodomain and the WUS-box domain, which is present
      in some members of the WOX protein family. The full-length ORF was subcloned into
      prokaryotic expression vector pET-30a, and an approximately 34-kDa protein was
      expressed in Escherichia coli BL21 (DE3) cells with IPTG induction. The molecular
      mass of the expressed protein was identical to that predicted by the cDNA
      sequence. Phylogenetic analysis suggested that Ae. tauschii WOX2 is closely
      related to the rice and maize orthologs. Quantitative PCR analysis showed that
      WOX2 from Ae. tauschii was primarily expressed in the seeds; transcription
      increased during seed development and declined after the embryos matured,
      suggesting that WOX2 is associated with embryo development in Ae. tauschii. 

PMID- 25983629
TI  - Differential expression of the pr1A gene in Metarhizium anisopliae and
      Metarhizium acridum across different culture conditions and during pathogenesis.
AB  - The entomopathogenic fungi of the genus Metarhizium have several subtilisin-like
      proteases that are involved in pathogenesis and these have been used to
      investigate genes that are differentially expressed in response to different
      growth conditions. The identification and characterization of these proteases can
      provide insight into how the fungus is capable of infecting a wide variety of
      insects and adapt to different substrates. In addition, the pr1A gene has been
      used for the genetic improvement of strains used in pest control. In this study
      we used quantitative RT-PCR to assess the relative expression levels of the pr1A
      gene in M. anisopliae and M. acridum during growth in different culture
      conditions and during infection of the sugar cane borer, Diatraea saccharalis
      Fabricius. We also carried out a pathogenicity test to assess the virulence of
      both species against D. saccharalis and correlated the results with the pattern
      of pr1A gene expression. This analysis revealed that, in both species, the pr1A
      gene was differentially expressed under the growth conditions studied and during
      the pathogenic process. M. anisopliae showed higher expression of pr1A in all
      conditions examined, when compared to M. acridum. Furthermore, M. anisopliae
      showed a greater potential to control D. saccharalis. Taken together, our results
      suggest that these species have developed different strategies to adapt to
      different growing conditions. 

PMID- 25983630
TI  - Genotoxic potential of the latex from cotton-leaf physicnut (Jatropha
      gossypiifolia L.).
AB  - Jatropha gossypiifolia L. (Euphorbiaceae), popularly known as cotton-leaf
      physicnut, is a milky shrub notable for its medicinal properties. The present
      study aimed to evaluate the toxic, cytotoxic and genotoxic effects of the latex
      of J. gossypiifolia, using Allium cepa L. as test system. Seeds of A. cepa were
      exposed to five concentrations of the latex (1.25; 2.5; 5; 10 and 20 mL/L) in
      order to evaluate parameters of toxicity (evaluation of root growth),
      cytotoxicity (mitotic index frequency) and genotoxicity (frequency of chromosome
      alterations). The latex showed a significant decrease in root mean growth value
      as well as mitotic index for the tested concentrations, except for 1.25 mL/L,
      when compared to results from the negative control. The 1.25, 2.5 and 5 mL/L
      concentrations induced significant chromo-some adherences, C-metaphases and/or
      chromosome bridges, as genotoxic effects. The significant frequency of chromosome
      bridges also indicated mutagenic potential for chromosomes of J. gossypiifolia as
      discussed in the paper. Considering that the latex is used in popular therapies,
      and that the test system A. cepa presents good correlation with tests carried out
      in mammals, it can be pointed out that its use for medicinal purposes may be
      harmful to human health especially if ingested. 

PMID- 25983631
TI  - Recombinogenic activity of Pantoprazole((r)) in somatic cells of Drosophila
      melanogaster.
AB  - Pantoprazole((r)) is one of the leading proton pump inhibitors (PPIs) used in the
      treatment of a variety of diseases related to the upper gastrointestinal tract.
      However, studies have shown an increased risk of developing gastric cancer,
      intestinal metaplasia and hyperplasia of endocrine cells with prolonged use. In
      the present study, the somatic mutation and recombination test (SMART) was
      employed to determine the mutagenic effects of Pantoprazole on Drosophila
      melanogaster. Repeated treatments with Pantoprazole were performed on 72-hour
      larvae of the standard (ST) and high bioactivation (HB) crosses at concentrations
      of 2.5, 5.0, and 10.0 MUM. In addition, doxorubicin (DXR) was administered at 0.4
      mM, as a positive control. When administered to ST descendants, total number of
      spots were statistically significant at 2.5 and 5.0 MUM concentrations. For HB
      descendants, a significant increase in the total number of spots was observed
      among the marked transheterozygous (MH) flies. Through analysis of balancer
      heterozygous (BH) descendants, recombinogenic effects were observed at all
      concentrations in descendants of the HB cross. In view of these experimental
      conditions and results, it was concluded that Pantoprazole is associated with
      recombinogenic effects in Drosophila melanogaster. 

PMID- 25983632
TI  - Enhanced tethered-flight duration and locomotor activity by overexpression of the
      human gene SOD1 in Drosophila motorneurons.
AB  - Mutation of the human gene superoxide dismutase (hSOD1) is associated with the
      fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou
      Gehrig's disease). Selective overexpression of hSOD1 in Drosophila motorneurons
      increases lifespan to 140% of normal. The current study was designed to determine
      resistance to lifespan decline and failure of sensorimotor functions by
      overexpressing hSOD1 in Drosophila's motorneurons. First, we measured the ability
      to maintain continuous flight and wingbeat frequency (WBF) as a function of age
      (5 to 50 days). Flies overexpressing hSOD1 under the D42-GAL4 activator were able
      to sustain flight significantly longer than controls, with the largest effect
      observed in the middle stages of life. The hSOD1-expressed line also had, on
      average, slower wingbeat frequencies in late, but not early life relative to age
      matched controls. Second, we examined locomotor (exploratory walking) behavior in
      late life when flies had lost the ability to fly (age >= 60 d). hSOD1-expressed
      flies showed significantly more robust walking activity relative to controls.
      Findings show patterns of functional decline dissimilar to those reported for
      other life-extended lines, and suggest that the hSOD1 gene not only delays death
      but enhances sensorimotor abilities critical to survival even in late life. 

PMID- 25983633
TI  - Neuroprotective changes in degeneration-related gene expression in the substantia
      nigra following acupuncture in an MPTP mouse model of Parkinsonism: Microarray
      analysis.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
      death of dopamine-generating cells in the substantia nigra (SN). Acupuncture
      stimulation results in an enhanced survival of dopaminergic neurons in the SN in
      Parkinsonism animal models. The present study investigated changes in gene
      expression profiles measured using whole transcript array in the SN region
      related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism model. In this model, acupuncture
      stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in
      the SN region; stimulation at non-acupoints did not suppress this decrease. Gene
      array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9,
      Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) probes that were up
      regulated in MPTP animals relative to controls were exclusively down-regulated by
      acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and
      Gm13931) probes that were down-regulated in MPTP animals compared to controls
      were exclusively up-regulated by acupuncture stimulation. These findings indicate
      that the 39 probes (12 annotated genes) affected by MPTP and acupuncture may be
      responsible for the inhibitory effects of acupuncture on degeneration-related
      gene expression in the SN following damage induced by MPTP intoxication. 

PMID- 25983634
TI  - Effects of Erosion from Mounds of Different Termite Genera on Distinct Functional
      Grassland Types in an African Savannah.
AB  - A key aspect of savannah vegetation heterogeneity is mosaics formed by two
      functional grassland types, bunch grasslands, and grazing lawns. We investigated
      the role of termites, important ecosystem engineers, in creating high-nutrient
      patches in the form of grazing lawns. Some of the ways termites can contribute to
      grazing lawn development is through erosion of soil from aboveground mounds to
      the surrounding soil surface. This may alter the nutrient status of the
      surrounding soils. We hypothesize that the importance of this erosion varies with
      termite genera, depending on feeding strategy and mound type. To test this, we
      simulated erosion by applying mound soil from three termite genera (Macrotermes,
      Odontotermes, and Trinervitermes) in both a field experiment and a greenhouse
      experiment. In the greenhouse experiment, we found soils with the highest macro
      nutrient levels (formed by Trinervitermes) promoted the quality and biomass of
      both a lawn (Digitaria longiflora) and a bunch (Sporobolus pyramidalis) grass
      species. In the field we found that soils with the highest micro nutrient levels
      (formed by Macrotermes) showed the largest increase in cover of grazing lawn
      species. By linking the different nutrient availability of the mounds to the
      development of different grassland states, we conclude that the presence of
      termite mounds influences grassland mosaics, but that the type of mound plays a
      crucial role in determining the nature of the effects.

PMID- 25983637
TI  - Squark and gluino production cross sections in [Formula: see text] collisions at
      [Formula: see text] and [Formula: see text] TeV.
AB  - We present state-of-the-art cross section predictions for the production of
      supersymmetric squarks and gluinos at the upcoming LHC run with a centre-of-mass
      energy of [Formula: see text] and [Formula: see text] TeV, and at potential
      future [Formula: see text] colliders operating at [Formula: see text] and
      [Formula: see text] TeV. The results are based on calculations which include the
      resummation of soft-gluon emission at next-to-leading logarithmic accuracy,
      matched to next-to-leading order supersymmetric QCD corrections. Furthermore, we
      provide an estimate of the theoretical uncertainty due to the variation of the
      renormalisation and factorisation scales and the parton distribution functions.

PMID- 25983638
TI  - Enveloping branes and brane-world singularities.
AB  - The existence of envelopes is studied for systems of differential equations in
      connection with the method of asymptotic splittings which allows one to determine
      the singularity structure of the solutions. The result is applied to brane-worlds
      consisting of a 3-brane in a five-dimensional bulk, in the presence of an analog
      of a bulk perfect fluid parameterizing a generic class of bulk matter. We find
      that all flat brane solutions suffer from a finite-distance singularity contrary
      to previous claims. We then study the possibility of avoiding finite-distance
      singularities by cutting the bulk and gluing regular solutions at the position of
      the brane. Further imposing physical conditions such as finite Planck mass on the
      brane and positive energy conditions on the bulk fluid, excludes, however, this
      possibility as well.

PMID- 25983640
TI  - Constraints on the [Formula: see text] form factor from analyticity and
      unitarity.
AB  - Motivated by the discrepancies noted recently between the theoretical
      calculations of the electromagnetic [Formula: see text] form factor and certain
      experimental data, we investigate this form factor using analyticity and
      unitarity in a framework known as the method of unitarity bounds. We use a QCD
      correlator computed on the spacelike axis by operator product expansion and
      perturbative QCD as input, and exploit unitarity and the positivity of its
      spectral function, including the two-pion contribution that can be reliably
      calculated using high-precision data on the pion form factor. From this
      information, we derive upper and lower bounds on the modulus of the [Formula: see
      text] form factor in the elastic region. The results provide a significant check
      on those obtained with standard dispersion relations, confirming the existence of
      a disagreement with experimental data in the region around [Formula: see text].

PMID- 25983641
TI  - Lepton flavor violation in flavored gauge mediation.
AB  - We study the anatomy and phenomenology of lepton flavor violation (LFV) in the
      context of flavored gauge mediation (FGM). Within FGM, the messenger sector
      couples directly to the MSSM matter fields with couplings controlled by the same
      dynamics that explains the hierarchies in the SM Yukawas. Although the pattern of
      flavor violation depends on the particular underlying flavor model, FGM provides
      a built-in flavor suppression similar to wave function renormalization or SUSY
      partial compositeness. Moreover, in contrast to these models, there is an
      additional suppression of left-right flavor transitions by third-generation
      Yukawas that in particular provides an extra protection against flavor-blind
      phases. We exploit the consequences of this setup for lepton flavor
      phenomenology, assuming that the new couplings are controlled by simple [Formula:
      see text] flavor models that have been proposed to accommodate large neutrino
      mixing angles. Remarkably, it turns out that in the context of FGM these models
      can pass the impressive constraints from LFV processes and leptonic electric
      dipole moments (EDMs) even for light superpartners, therefore offering the
      possibility of resolving the longstanding muon [Formula: see text] anomaly.

PMID- 25983642
TI  - The NUHM2 after LHC Run 1.
AB  - We make a frequentist analysis of the parameter space of the NUHM2, in which the
      soft supersymmetry (SUSY)-breaking contributions to the masses of the two Higgs
      multiplets, [Formula: see text], vary independently from the universal soft SUSY
      breaking contributions [Formula: see text] to the masses of squarks and sleptons.
      Our analysis uses the MultiNest sampling algorithm with over [Formula: see text]
      points to sample the NUHM2 parameter space. It includes the ATLAS and CMS Higgs
      mass measurements as well as the ATLAS search for supersymmetric jets + [Formula:
      see text] signals using the full LHC Run 1 data, the measurements of [Formula:
      see text] by LHCb and CMS together with other B-physics observables, electroweak
      precision observables and the XENON100 and LUX searches for spin-independent dark
      matter scattering. We find that the preferred regions of the NUHM2 parameter
      space have negative SUSY-breaking scalar masses squared at the GUT scale for
      squarks and sleptons, [Formula: see text], as well as [Formula: see text]. The
      tension present in the CMSSM and NUHM1 between the supersymmetric interpretation
      of [Formula: see text] and the absence to date of SUSY at the LHC is not
      significantly alleviated in the NUHM2. We find that the minimum [Formula: see
      text] with 21 degrees of freedom (dof) in the NUHM2, to be compared with
      [Formula: see text] in the CMSSM, and [Formula: see text] in the NUHM1. We find
      that the one-dimensional likelihood functions for sparticle masses and other
      observables are similar to those found previously in the CMSSM and NUHM1.

PMID- 25983643
TI  - TMDlib and TMDplotter: library and plotting tools for transverse-momentum
      dependent parton distributions.
AB  - Transverse-momentum-dependent distributions (TMDs) are extensions of collinear
      parton distributions and are important in high-energy physics from both
      theoretical and phenomenological points of view. In this manual we introduce the
      library [Formula: see text], a tool to collect transverse-momentum-dependent
      parton distribution functions (TMD PDFs) and fragmentation functions (TMD FFs)
      together with an online plotting tool, TMDplotter. We provide a description of
      the program components and of the different physical frameworks the user can
      access via the available parameterisations.

PMID- 25983645
TI  - TeO[Formula: see text] bolometers with Cherenkov signal tagging: towards next
      generation neutrinoless double-beta decay experiments.
AB  - CUORE, an array of 988 TeO[Formula: see text] bolometers, is about to be one of
      the most sensitive experiments searching for neutrinoless double-beta decay. Its
      sensitivity could be further improved by removing the background from [Formula:
      see text] radioactivity. A few years ago it was pointed out that the signal from
      [Formula: see text]s can be tagged by detecting the emitted Cherenkov light,
      which is not produced by [Formula: see text]s. In this paper we confirm this
      possibility. For the first time we measured the Cherenkov light emitted by a
      CUORE crystal, and found it to be 100 eV at the [Formula: see text]-value of the
      decay. To completely reject the [Formula: see text] background, we compute that
      one needs light detectors with baseline noise below 20 eV RMS, a value which is 3
      4 times smaller than the average noise of the bolometric light detectors we are
      using. We point out that an improved light detector technology must be developed
      to obtain TeO[Formula: see text] bolometric experiments able to probe the
      inverted hierarchy of neutrino masses.

PMID- 25983647
TI  - Sterile neutrino dark matter and low scale leptogenesis from a charged scalar.
AB  - We show that novel paths to dark matter generation and baryogenesis are open when
      the standard model is extended with three sterile neutrinos [Formula: see text]
      and a charged scalar [Formula: see text]. Specifically, we propose a new
      production mechanism for the dark matter particle-a multi-keV sterile neutrino,
      [Formula: see text]-that does not depend on the active-sterile mixing angle and
      does not rely on a large primordial lepton asymmetry. Instead, [Formula: see
      text] is produced, via freeze-in, by the decays of [Formula: see text] while it
      is in equilibrium in the early Universe. In addition, we demonstrate that, thanks
      to the couplings between the heavier sterile neutrinos [Formula: see text] and
      [Formula: see text], baryogenesis via leptogenesis can be realized close to the
      electroweak scale. The lepton asymmetry is generated either by [Formula: see
      text]-decays for masses [Formula: see text] TeV, or by [Formula: see text]
      oscillations for [Formula: see text] GeV. Experimental signatures of this
      scenario include an X-ray line from dark matter decays, and the direct production
      of [Formula: see text] at the LHC. This model thus describes a minimal, testable
      scenario for neutrino masses, the baryon asymmetry, and dark matter.

PMID- 25983650
TI  - Automated NNLL [Formula: see text] NLO resummation for jet-veto cross sections.
AB  - In electroweak-boson production processes with a jet veto, higher-order
      corrections are enhanced by logarithms of the veto scale over the invariant mass
      of the boson system. In this paper, we resum these Sudakov logarithms at next-to
      next-to-leading logarithmic accuracy and match our predictions to next-to-leading
      order (NLO) fixed-order results. We perform the calculation in an automated way,
      for arbitrary electroweak final states and in the presence of kinematic cuts on
      the leptons produced in the decays of the electroweak bosons. The resummation is
      based on a factorization theorem for the cross sections into hard functions,
      which encode the virtual corrections to the boson production process, and beam
      functions, which describe the low-[Formula: see text] emissions collinear to the
      beams. The one-loop hard functions for arbitrary processes are calculated using
      the MadGraph5_aMC@NLO framework, while the beam functions are process
      independent. We perform the resummation for a variety of processes, in particular
      for [Formula: see text] pair production followed by leptonic decays of the
      [Formula: see text] bosons.

PMID- 25983651
TI  - Modified gravity from the nonperturbative quantization of a metric.
AB  - Based on certain assumptions for the expectation value of a product of the
      quantum fluctuating metric at two points, the gravitational and scalar field
      Lagrangians are evaluated. Assuming a vanishing expectation value of the first
      order terms of the metric, the calculations are performed with an accuracy of
      second order. It is shown that such quantum corrections give rise to modified
      gravity.

PMID- 25983652
TI  - Searching for dark matter at colliders.
AB  - Dark Matter (DM) detection prospects at future [Formula: see text] colliders are
      reviewed under the assumption that DM particles are fermions of the Majorana or
      Dirac type. Although the discussion is quite general, one will keep in mind the
      recently proposed candidate based on an excess of energetic photons observed in
      the center of our Galaxy with the Fermi-LAT satellite. In the first part we will
      assume that DM interactions are mediated by vector bosons, [Formula: see text] or
      [Formula: see text]. In the case of [Formula: see text]-boson Direct Detection
      limits force only axial couplings with the DM. This solution can be naturally
      accommodated by Majorana DM but is disfavored by the GC excess. Viable scenarios
      can be instead found in the case of [Formula: see text] mediator. These scenarios
      can be tested at [Formula: see text] colliders through ISR events, [Formula: see
      text]. A sensitive background reduction can be achieved by using highly polarized
      beams. In the second part scalar particles, in particular Higgs particles, have
      been considered as mediators. The case of the SM Higgs mediator is excluded by
      limits on the invisible branching ratio of the Higgs. On the contrary
      particularly interesting is the case in which the DM interactions are mediated by
      the pseudoscalar state [Formula: see text] in two Higgs-doublet model scenarios.
      In this last case the main collider signature is [Formula: see text].

PMID- 25983653
TI  - The effective Planck mass and the scale of inflation.
AB  - Observable quantities in cosmology are dimensionless, and therefore independent
      of the units in which they are measured. This is true of all physical quantities
      associated with the primordial perturbations that source cosmic microwave
      background anisotropies such as their amplitude and spectral properties. However,
      if one were to try and infer an absolute energy scale for inflation-a priori, one
      of the more immediate corollaries of detecting primordial tensor modes-one
      necessarily makes reference to a particular choice of units, the natural choice
      for which is Planck units. In this note, we discuss various aspects of how
      inferring the energy scale of inflation is complicated by the fact that the
      effective strength of gravity as seen by inflationary quanta necessarily differs
      from that seen by gravitational experiments at presently accessible scales. The
      uncertainty in the former relative to the latter has to do with the unknown
      spectrum of universally coupled particles between laboratory scales and the
      putative scale of inflation. These intermediate particles could be in hidden as
      well as visible sectors or could also be associated with Kaluza-Klein resonances
      associated with a compactification scale below the scale of inflation. We discuss
      various implications for cosmological observables.

PMID- 25983655
TI  - A hell of a life: addiction and marginality in post-industrial Detroit.
AB  - Drawing on concepts from Foucault and Agamben, we maintain that the lives of
      daily heroin users provide a prime illustration of bare life in the zone of
      indistinction that is contemporary Detroit. First, we consider the case of
      Detroit as a stigmatized and racially segregated city, with concrete consequences
      for its residents. We then present evidence from in-depth ethnographic and
      economic interviews to illustrate the various spaces of confinement-that of
      addiction, that of economic marginality, and that of gender-occupied by these men
      and women, as well as the indeterminacy of their daily lives, captured through
      their descriptions of daily routines and interactions. We examine their
      expressions of worth as expressed in economic, emotional and moral terms.
      Finally, we draw connections between the sustained marginality of these
      individuals, as a contemporary category of homo sacer, and the policies and
      powers that both despise and depend upon them. Heroin, we contend, helps to fill
      and numb this social void, making bare life bearable, but also cementing one's
      marginality into semi-permanence.

PMID- 25983656
TI  - Trees increase their P:N ratio with size.
AB  - AIM: Phosphorus (P) tends to become limiting in aging terrestrial ecosystems, and
      its resorption efficiency is higher than for other elements such as nitrogen (N).
      We thus hypothesized that trees should store more P than those other elements
      such as N when tree size increases and that this process should be enhanced in
      slow-growing late successional trees. LOCATION: Catalan forests. METHODS: We have
      used data from the Catalan Forest Inventory that contains field data of the P and
      N contents of total aboveground, foliar and woody biomasses of the diverse
      Mediterranean, temperate and alpine forests of Catalonia (1018 sites). We used
      correlation and general lineal models (GLM) to analyze the allometric
      relationships between nutrient contents of different aboveground biomass
      fractions (foliar, branches and stems) and total aboveground biomass. RESULTS:
      Aboveground forest P content increases proportionally more than aboveground
      forest N content with increasing aboveground biomass. Two mechanisms underlie
      this. First, woody biomass increases proportionally more than foliar biomass
      having woody biomass higher P:N ratio than foliar biomass. Second, wood P:N ratio
      increases with tree size. These results are consistent with the generally higher
      foliar resorption of P than of N. Slow-growing species accumulate more P in total
      aboveground with size than fast-growing species mainly as a result of their large
      capacity to store P in wood. MAIN CONCLUSIONS: Trees may have thus developed long
      term adaptive mechanisms to store P in biomass, mainly in wood, thereby slowing
      the loss of P from the ecosystems, reducing its availability for competitors, and
      implying an increase in the P:N ratio in forest biomass with aging. This trend to
      accumulate more P than N with size is more accentuated in slow-growing, large,
      long-living species of late successional stages. This way they partly
      counterbalance the gradual decrease of P in the soil.

PMID- 25983657
TI  - Comparison of a restrictive versus liberal red cell transfusion policy for
      patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow
      failure disorders.
AB  - This is the protocol for a review and there is no abstract. The objectives are as
      follows: To assess the efficacy and safety of a restrictive versus liberal red
      cell transfusion strategy for patients with long-term bone marrow failure. These
      include myelodysplasia, acquired aplastic anaemia, and other inherited bone
      marrow failure disorders.

PMID- 25983659
TI  - European medicines agency guideline for biological medicinal products: a further
      step for a safe use of biosimilars.

PMID- 25983658
TI  - B-cell receptor-guided delivery of peptide-siRNA complex for B-cell lymphoma
      therapy.
AB  - BACKGROUND: Despite the clinical response of conventional anticancer therapy,
      including chemotherapeutic treatments, radiation therapy and corticosteroids,
      tumorigenic B-cell lymphomas show an incomplete response to clinical practices
      that result in a minimal residual disease (MRD) where few residual neoplastic
      cells undetected in vivo, replenish the cancer cell reservoir. This scenario,
      which is also shared with other cancer diseases, requires the development of
      strategies to advance in novel, selective targeting toward the tumorigenic cells
      that survive to the anticancer agents. METHODS: Here, we have taken advantage of
      the therapeutic properties of an idiotype specific peptide (pA20-36) that bind
      specifically to murine B-lymphoma cells in the setting of an anti cancer
      strategy, based on the selected delivery of electrostatic-based complex, peptide
      siRNA. To this end, two engineered, arginine rich, peptides that included the
      pA20-36 targeting sequence were designed to bind fluorescent-labelled siRNA. One
      peptide presented 9 Arg at the C-terminal of pA20-36 whereas the other included 5
      Arg at the N- and C-terminus, respectively. RESULTS: Compared to the control and
      random peptide-siRNA complexes, both pA20-36-siRNA complexes were endowed with
      the selective delivering of fluorescent-labelled siRNA toward the A20 murine B
      cell lymphoma, as evaluated by cytofluorimetry and confocal microscopy, whereas
      fluorescent-labelled siRNA alone was not internalized in the selected cells.
      Compared to peptide controls, the use of the modified pA20-36 peptides complexed
      with siRNA anti-GAPDH and anti-Bcl2 showed a down-regulation in the expression
      levels of the corresponding genes. CONCLUSIONS: Peptide-siRNA complex can be
      suitable tool for both selective peptide-driven cell targeting and gene
      silencing. In this setting, the improvement of this strategy is expected to
      provide a safe and non-invasive approach for the delivery of therapeutic
      molecules.

PMID- 25983660
TI  - CD151: Basis Sequence: Mouse.

PMID- 25983661
TI  - ALCAM: Basis Sequence: Mouse.

PMID- 25983662
TI  - Determinants of access to pediatric hospice care: A conceptual model.
AB  - One of the many difficult moments for families of children with life-limiting
      illnesses is to make the decision to access pediatric hospice care. Although
      determinants that influence families' decisions to access pediatric hospice care
      have been recently identified, the relationship between these determinants and
      access to pediatric hospice care have not been explicated or grounded in accepted
      healthcare theories or models. Using the Andersen Behavioral Healthcare
      Utilization Model, this article presents a conceptual model describing the
      determinants of hospice access. Predisposing (demographic; social support; and
      knowledge, beliefs, and values), enabling (family and community resources) and
      need (perceived and evaluated needs) factors were identified through the use of
      hospice literature. The relationships among these factors are described and
      implications of the model for future study and practice are discussed.

PMID- 25983663
TI  - Community Disasters, Psychological Trauma, and Crisis Intervention.
AB  - The current issue of International Journal of Emergency Mental Health and Human
      Resilience is focused on community disasters, the impact of trauma exposure, and
      crisis intervention. The articles incorporated include studies ranging from the
      World Trade Center disaster to Hurricane Sandy. These studies are related to
      public attitudes and beliefs about disease outbreaks, the impact of volunteerism
      following the World Trade Center attacks, alcohol misuse among police officers
      after Hurricane Katrina, posttraumatic stress disorder after Hurricane Sandy
      among those exposed to the Trade Center disaster, compassion fatigue and burnout
      among trauma workers, crisis interventions in Eastern Europe, and police
      officers' use of stress intervention services. While this scope is broad, it
      reflects the knowledge that has emerged since the Buffalo Creek and Chernobyl
      catastrophes, to the more recent Hurricane Katrina and Sandy disasters. Given the
      current threat environment, psychologists, social workers, and other providers
      need to be aware of these developments and be prepared to mitigate the impact of
      psychological trauma following community disasters, whether natural or man-made.

PMID- 25983664
TI  - The Role of Infant Temperament in Stability and Change in Coparenting Across the
      First Year of Life.
AB  - OBJECTIVE: The current study investigated the role of infant temperament in
      stability and change in coparenting behavior across the infant's first year.
      Specifically, bidirectional relations between infant temperament and coparenting
      were examined and temperament was further considered as a moderator of
      longitudinal stability in coparenting behavior. DESIGN: Fifty-six two-parent
      families were recruited to participate during their third trimester of pregnancy.
      Coparenting behavior was assessed in families' homes when infants were age 3.5
      months and in a laboratory setting at 13 months postpartum. Mothers and fathers
      also reported on their infant's temperamental difficulty at 3.5 and 13 months.
      RESULTS: Evidence for bidirectional relations between infant temperament and
      coparenting was obtained. Early infant difficulty, as reported by fathers, was
      associated with a decrease in supportive coparenting behavior across time;
      conversely, early supportive coparenting behavior was associated with a decrease
      in infant difficulty. Moreover, infant difficult temperament moderated stability
      in undermining coparenting behavior, such that undermining behavior at 3.5 months
      predicted undermining behavior at 13 months only when infants had less difficult
      temperaments. CONCLUSIONS: These findings suggest that infants may play a role in
      the early course of the family processes that shape their development. With
      respect to practice, these results suggest that early intervention in the
      coparenting subsystem is essential for families, particularly those with
      temperamentally difficult infants.

PMID- 25983665
TI  - For the Mouths of Babes: Nutrition Literacy Outreach to a Child Care Center.
AB  - Childhood obesity is at crisis levels in the United States. Risk factors for
      obesity can begin as early as infancy. Approximately 12 million children up to
      five years of age spend about 22.5 hours per week in child care centers where
      they receive a significant portion of their daily nutrition. Child care center
      personnel may not know how to select nutritious meal and snack choices. A health
      sciences librarian, a child care center director and a dietitian designed an
      outreach program on nutrition that helped child care center teachers gain
      increased nutrition literacy. The teachers indicated that they gained increased
      personal understanding of formerly confusing nutrition issues (e.g., how to read
      a nutrition label and what defines a whole grain). Teachers were also able to
      identify aspects of web sites linked from MedlinePlus that indicated the sites
      served as reliable sources of health information.

PMID- 25983666
TI  - Educating K-12 Professionals and Parents: Finding Health Information for Special
      Needs Children.
AB  - A successful partnership model between an academic health sciences library and a
      K-12 school district to provide librarians, nurses, and special education staff
      with access to health information to support special needs children and their
      parents is presented. Train-the-trainer staff sessions and a parent session were
      collaboratively developed. Funding support was used to purchase iPads for
      librarians and nurses to deliver mobile support. The results indicate the
      resources taught are being used to find health information and the school
      librarians and nurses are being sought after to assist in finding health
      information. Positive feedback from the school district indicates this model
      could be replicated in similar settings.

PMID- 25983668
TI  - An Approach to Measuring Dispersed Families with a Particular Focus on Children
      'Left Behind' by Migrant Parents: Findings from Rural South Africa.
AB  - There is growing policy and academic interest in the conditions, experiences, and
      well-being of migrant families stretched across origin and destination
      households. In South Africa, the dispersal of children and migrant parents across
      multiple households is a commonplace childhood experience. However, in common
      with the broader international context, quantitative analyses of the social and
      residential connections between children and migrant parents in South Africa have
      been limited by the lack of available data that document family arrangements from
      the perspective of more than one household. This paper describes a new data
      collection effort in the origin and destination households of migrants from rural
      KwaZulu-Natal and explains the methodology for using this data to examine
      multiple household contexts for children and parents. In order to illustrate the
      contribution that this form of data collection effort could make to family
      migration studies, the paper also presents results on the living arrangements of
      children 'left behind' by migrant parents; a potentially vulnerable group whose
      arrangements are challenging to examine with existing data sources. The empirical
      results show the majority (75%) of left behind children have previously migrated
      and a significant proportion of migrants' children (25%) were not living in their
      parent's origin or destination household. The findings highlight the need for
      careful measurement of the circumstances of left behind children and demonstrate
      the contribution of linked data for providing insights into the residential
      arrangements of migrants' children. (c) 2014 The Authors. Population, Space and
      Place published by John Wiley & Sons Ltd.

PMID- 25983667
TI  - Understanding Family Migration in Rural South Africa: Exploring Children's
      Inclusion in the Destination Households of Migrant Parents.
AB  - Despite the removal of restrictions on movement and increasing female
      participation in migration, only a minority of migrant parents in South Africa
      include their children in their destination household. Quantitative analyses of
      the circumstances in which children accompany a migrant parent have been limited
      by the lack of available data that document family arrangements from the
      perspective of more than one household. This paper uses data about members of
      rural households in a demographic surveillance population in KwaZulu-Natal and a
      linked sample survey of adult migrants to examine factors associated with
      children's inclusion in the destination household of migrant parents, analyse the
      timing and sequence of children's moves to parental destination households, and
      describe the composition of parental origin and destination households. The
      findings confirm that in contemporary South Africa, only a small percentage (14%)
      of migrants' children who are members of the parental origin household are also
      members of the parental destination household. Membership of the parental
      destination household is associated with parental characteristics and the child's
      age, but not measures of socio-economic status, and children most commonly
      migrate several years after their migrant parent. Children included in the
      destination household of migrant fathers frequently live in small households,
      which also include their mother, whereas children included in the destination
      household of migrant mothers live in larger households. This study contributes to
      understanding the contexts of children's inclusion in parental destination
      households in South Africa and demonstrates the potential of data collected in
      migrants' origin and destination households.

PMID- 25983670
TI  - Personality, Cognitive Style, Motivation, and Aptitude Predict Systematic Trends
      in Analytic Forecasting Behavior.
AB  - The decision sciences are increasingly challenged to advance methods for modeling
      analysts, accounting for both analytic strengths and weaknesses, to improve
      inferences taken from increasingly large and complex sources of data. We examine
      whether psychometric measures-personality, cognitive style, motivated cognition
      predict analytic performance and whether psychometric measures are competitive
      with aptitude measures (i.e., SAT scores) as analyst sample selection criteria. A
      heterogeneous, national sample of 927 participants completed an extensive battery
      of psychometric measures and aptitude tests and was asked 129 geopolitical
      forecasting questions over the course of 1 year. Factor analysis reveals four
      dimensions among psychometric measures; dimensions characterized by differently
      motivated "top-down" cognitive styles predicted distinctive patterns in aptitude
      and forecasting behavior. These dimensions were not better predictors of
      forecasting accuracy than aptitude measures. However, multiple regression and
      mediation analysis reveals that these dimensions influenced forecasting accuracy
      primarily through bias in forecasting confidence. We also found that these facets
      were competitive with aptitude tests as forecast sampling criteria designed to
      mitigate biases in forecasting confidence while maximizing accuracy. These
      findings inform the understanding of individual difference dimensions at the
      intersection of analytic aptitude and demonstrate that they wield predictive
      power in applied, analytic domains.

PMID- 25983671
TI  - A general formalism for the determination of the effective mass of the nanoscale
      structural inhomogeneities of the domain wall in uniaxial ferromagnets.
AB  - On the basis of the method of gyrotropic Thiele forces, we build a formalism that
      allows the determination of the effective mass of the nanoscales structural
      elements of the domain wall (DW): vertical Bloch line and Bloch point in uniaxial
      ferromagnets. As shown, the effective mass of these magnetic inhomogeneities
      depends on the value of the gyrotropic domain wall bend that is created by their
      movement. 

PMID- 25983669
TI  - Influence of a montmorency cherry juice blend on indices of exercise-induced
      stress and upper respiratory tract symptoms following marathon running--a pilot
      investigation.
AB  - BACKGROUND: Prolonged exercise, such as marathon running, has been associated
      with an increase in respiratory mucosal inflammation. The aim of this pilot study
      was to examine the effects of Montmorency cherry juice on markers of stress,
      immunity and inflammation following a Marathon. METHODS: Twenty recreational
      Marathon runners consumed either cherry juice (CJ) or placebo (PL) before and
      after a Marathon race. Markers of mucosal immunity secretory immunoglobulin A
      (sIgA), immunoglobulin G (IgG), salivary cortisol, inflammation (CRP) and self
      reported incidence and severity of upper respiratory tract symptoms (URTS) were
      measured before and following the race. RESULTS: All variables except secretory
      IgA and IgG concentrations in saliva showed a significant time effect (P <0.01).
      Serum CRP showed a significant interaction and treatment effect (P < 0.01). The
      CRP increase at 24 and 48 h post-Marathon was lower (P < 0.01) in the CJ group
      compared to PL group. Mucosal immunity and salivary cortisol showed no
      interaction effect or treatment effect. The incidence and severity of URTS was
      significantly greater than baseline at 24 h and 48 h following the race in the PL
      group and was also greater than the CJ group (P < 0.05). No URTS were reported in
      the CJ group whereas 50 % of runners in the PL group reported URTS at 24 h and 48
      h post-Marathon. CONCLUSIONS: This is the first study that provides encouraging
      evidence of the potential role of Montmorency cherries in reducing the
      development of URTS post-Marathon possibly caused by exercise-induced
      hyperventilation trauma, and/or other infectious and non-infectious factors.

PMID- 25983672
TI  - The influence of process parameters and pulse ratio of precursors on the
      characteristics of La1 - x Al x O3 films deposited by atomic layer deposition.
AB  - The influence of processing parameters of aluminum oxide (Al2O3) and lanthanum
      oxide (La2O3) gate dielectric is investigated. Trimethylaluminum (TMA) and
      tris(isopropylcyclopentadienyl) lanthanum [La(iPrCp)3] were used as precursors
      separately, and H2O was used as oxidant. The ultra-thin La1 - x Al x O3 gate
      dielectric films are deposited on p-type silicon substrates by atom layer
      deposition (ALD) for different pulse ratios of precursors. Effects of different
      La/Al precursor pulse ratios on the physical properties and electrical
      characteristics of La1 - x Al x O3 films are studied. The preliminary testing
      results indicate that the increase of La precursor pulse can improve the
      characteristics of film, which has significant effects on the dielectric
      constant, equivalent oxide thickness (EOT), electrical properties, and stability
      of film. 

PMID- 25983673
TI  - Formation of dimers of light noble atoms under encapsulation within fullerene's
      voids.
AB  - Van der Waals (vdW) He2 diatomic trapped inside buckminsterfullerene's void and
      preserving its diatomic bonding is itself a controversial phenomenon due to the
      smallness of the void diameter comparing to the He-He equilibrium distance. We
      propound a computational approach, including smaller fullerenes, C20 and C28, to
      demonstrate that encapsulation of He2 inside the studied fullerenes exhibits an
      interesting quantum behavior resulting in a binding at shorter, non-vdW
      internuclear distances, and we develop a computational model to interpret these
      He-He bonding patterns in terms of Bader's atom-in-molecule theory. We also
      conjecture a computational existence of He2@C60 on a solid basis of its
      theoretical UV absorption spectrum and a comparison with that of C60. 

PMID- 25983675
TI  - Yoga as a method of symptom management in multiple sclerosis.
AB  - Multiple Sclerosis (MS) is an immune-mediated process in which the body's immune
      system damages myelin in the central nervous system (CNS). The onset of this
      disorder typically occurs in young adults, and it is more common among women.
      Currently, there is no cure and the long-term disease progression makes
      symptomatic management critical for maintaining quality of life. Several
      pharmacotherapeutic agents are approved for treatment, but many patients seek
      complementary and alternative interventions. Reviews have been conducted
      regarding broad topics such as mindfulness-based interventions for people
      diagnosed with MS and the impact of yoga on a range of neurological disorders.
      The objective of the present review is to examine the potential benefits of yoga
      for individuals with MS and address its use in managing symptoms including pain,
      mental health, fatigue, spasticity, balance, bladder control, and sexual
      function. 

PMID- 25983674
TI  - Metabolomics analysis reveals insights into biochemical mechanisms of mental
      stress-induced left ventricular dysfunction.
AB  - Mental stress induced left ventricular dysfunction (LVD) has been associated with
      a greater risk of adverse events in coronary heart disease (CHD) patients
      independent of conventional risk indicators. The underlying biochemical
      mechanisms of this cardiovascular condition are poorly understood. Our objective
      was to use metabolomics technology to identify biochemical changes that co-occur
      with mental stress-induced LVD in patients with clinically stable CHD.
      Participants were adult CHD patients who were recruited for mental stress-induced
      myocardial ischemia screening. For this study, we randomly selected 30 patients
      representing the extremes of the mental stress-induced left ventricular ejection
      fraction (LVEF) change distribution; 15 who showed LVD (i.e. LVEF reduction >=5)
      and 15 who showed a normal left ventricular response (NLVR; i.e. a LVEF increase
      of >=5) to three mental stressors. An electrochemistry based metabolomics
      platform was used to profile pre- and post-stress serum samples yielding data for
      22 known compounds, primarily within the tyrosine, tryptophan, purine and
      methionine pathways. There were significant stress-induced changes in several
      compounds. A comparison between the NLVR and LVD groups showed significant
      effects for kynurenine (p = .036, N-acetylserotonin (p = .054), uric acid (p =
      .015), tyrosine (p = .019) and a trend for methionine (p = .065); the NLVR group
      showed a significantly greater stress-induced reduction in all of those compounds
      compared to the LVD group. Many of these biochemicals have been implicated in
      other stress-related phenomena and are plausible candidates for mechanisms
      underlying LVD in response to mental stress.

PMID- 25983676
TI  - Using neurophysiological signals that reflect cognitive or affective state: six
      recommendations to avoid common pitfalls.
AB  - Estimating cognitive or affective state from neurophysiological signals and
      designing applications that make use of this information requires expertise in
      many disciplines such as neurophysiology, machine learning, experimental
      psychology, and human factors. This makes it difficult to perform research that
      is strong in all its aspects as well as to judge a study or application on its
      merits. On the occasion of the special topic "Using neurophysiological signals
      that reflect cognitive or affective state" we here summarize often occurring
      pitfalls and recommendations on how to avoid them, both for authors (researchers)
      and readers. They relate to defining the state of interest, the
      neurophysiological processes that are expected to be involved in the state of
      interest, confounding factors, inadvertently "cheating" with classification
      analyses, insight on what underlies successful state estimation, and finally, the
      added value of neurophysiological measures in the context of an application. We
      hope that this paper will support the community in producing high quality studies
      and well-validated, useful applications. 

PMID- 25983677
TI  - A novel rat model of blast-induced traumatic brain injury simulating different
      damage degree: implications for morphological, neurological, and biomarker
      changes.
AB  - In current military conflicts and civilian terrorism, blast-induced traumatic
      brain injury (bTBI) is the primary cause of neurotrauma. However, the effects and
      mechanisms of bTBI are poorly understood. Although previous researchers have made
      significant contributions to establishing animal models for the simulation of
      bTBI, the precision and controllability of blast-induced injury in animal models
      must be improved. Therefore, we established a novel rat model to simulate blast
      wave injury to the brain. To simulate different extents of bTBI injury, the
      animals were divided into moderate and severe injury groups. The miniature
      spherical explosives (pentaerythritol tetranitrate) used in each group were of
      different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter
      in the severe injury group). A specially designed apparatus was able to precisely
      adjust the positions of the miniature explosives and create eight rats with bTBI
      simultaneously, using a single electric detonator. Neurological functions, gross
      pathologies, histopathological changes and the expression levels of various
      biomarkers were examined after the explosion. Compared with the moderate injury
      group, there were significantly more neurological dysfunctions, cortical
      contusions, intraparenchymal hemorrhages, cortical expression of S-100beta,
      myelin basic protein, neuron-specific enolase, IL-8, IL-10, inducible nitric
      oxide synthase, and HIF-1alpha in the severe injury group. These results
      demonstrate that we have created a reliable and reproducible bTBI model in rats.
      This model will be helpful for studying the mechanisms of bTBI and developing
      strategies for clinical bTBI treatment. 

PMID- 25983678
TI  - A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the
      abundant granule cells during motor control.
AB  - The cerebellar granule cells (GCs) have been proposed to perform lossless,
      adaptive spatio-temporal coding of incoming sensory/motor information required by
      downstream cerebellar circuits to support motor learning, motor coordination, and
      cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar
      neuronal network (biCNN) to selectively enable/disable the output of GCs and
      evaluate the behavioral and neural consequences during three different control
      scenarios. The control scenarios are a simple direct current motor (1 degree of
      freedom: DOF), an unstable two-wheel balancing robot (2 DOFs), and a simulation
      model of a quadcopter (6 DOFs). Results showed that adequate control was
      maintained with a relatively small number of GCs (< 200) in all the control
      scenarios. However, the minimum number of GCs required to successfully govern
      each control plant increased with their complexity (i.e., DOFs). It was also
      shown that increasing the number of GCs resulted in higher robustness against
      changes in the initialization parameters of the biCNN model (i.e., synaptic
      connections and synaptic weights). Therefore, we suggest that the abundant GCs in
      the cerebellar cortex provide the computational power during the large repertoire
      of motor activities and motor plants the cerebellum is involved with, and bring
      robustness against changes in the cerebellar microcircuit (e.g., neuronal
      connections). 

PMID- 25983679
TI  - Animal models of spontaneous activity in the healthy and impaired auditory
      system.
AB  - Spontaneous neural activity in the auditory nerve fibers and in auditory cortex
      in healthy animals is discussed with respect to the question: Is spontaneous
      activity noise or information carrier? The studies reviewed suggest strongly that
      spontaneous activity is a carrier of information. Subsequently, I review the
      numerous findings in the impaired auditory system, particularly with reference to
      noise trauma and tinnitus. Here the common assumption is that tinnitus reflects
      increased noise in the auditory system that among others affects temporal
      processing and interferes with the gap-startle reflex, which is frequently used
      as a behavioral assay for tinnitus. It is, however, more likely that the
      increased spontaneous activity in tinnitus, firing rate as well as neural
      synchrony, carries information that shapes the activity of downstream structures,
      including non-auditory ones, and leading to the tinnitus percept. The main
      drivers of that process are bursting and synchronous firing, which facilitates
      transfer of activity across synapses, and allows formation of auditory objects,
      such as tinnitus. 

PMID- 25983649
TI  - Search for long-lived particles decaying to jet pairs.
AB  - A search is presented for long-lived particles with a mass between 25 and 50
      [Formula: see text] and a lifetime between 1 and 200[Formula: see text] in a
      sample of proton-proton collisions at a centre-of-mass energy of [Formula: see
      text] TeV, corresponding to an integrated luminosity of 0.62 [Formula: see text],
      collected by the LHCb detector. The particles are assumed to be pair-produced by
      the decay of a standard model-like Higgs boson. The experimental signature of the
      long-lived particle is a displaced vertex with two associated jets. No excess
      above the background is observed and limits are set on the production cross
      section as a function of the long-lived particle mass and lifetime.

PMID- 25983680
TI  - Alterations in dendrite and spine morphology of cortical pyramidal neurons in
      DISC1-binding zinc finger protein (DBZ) knockout mice.
AB  - Dendrite and dendritic spine formation are crucial for proper brain function.
      DISC1-binding zinc finger protein (DBZ) was first identified as a Disrupted-In
      Schizophrenia1 (DISC1) binding partner. DBZ is highly expressed in the cerebral
      cortex of developing and adult rodents and is involved in neurite formation, cell
      positioning, and the development of interneurons and oligodendrocytes. The
      functional roles of DBZ in postnatal brain remain unknown; thus we investigated
      cortical pyramidal neuron morphology in DBZ knockout (KO) mice. Morphological
      analyses by Golgi staining alone in DBZ KO mice revealed decreased dendritic
      arborization, increased spine density. A morphological analysis of the spines
      revealed markedly increased numbers of thin spines. To investigate whole spine
      structure in detail, electron tomographic analysis using ultra-high voltage
      electron microscopy (UHVEM) combined with Golgi staining was performed. Tomograms
      and three-dimensional models of spines revealed that the spines of DBZ KO mice
      exhibited two types of characteristic morphology, filopodia-like spines and
      abnormal thin-necked spines having an extremely thin spine neck. Moreover,
      conventional electron microscopy revealed significantly decreased number of
      postsynaptic densities (PSDs) in spines of DBZ KO mice. In conclusion, DBZ
      deficiency impairs the morphogenesis of dendrites and spines in cortical
      pyramidal neurons. 

PMID- 25983681
TI  - Pro-social 50-kHz ultrasonic communication in rats: post-weaning but not post
      adolescent social isolation leads to social impairments-phenotypic rescue by re
      socialization.
AB  - Rats are highly social animals and social play during adolescence has an
      important role for social development, hence post-weaning social isolation is
      widely used to study the adverse effects of juvenile social deprivation and to
      induce behavioral phenotypes relevant to neuropsychiatric disorders, like
      schizophrenia. Communication is an important component of the rat's social
      behavior repertoire, with ultrasonic vocalizations (USV) serving as situation
      dependent affective signals. High-frequency 50-kHz USV occur in appetitive
      situations and induce approach behavior, supporting the notion that they serve as
      social contact calls; however, post-weaning isolation effects on the behavioral
      changes displayed by the receiver in response to USV have yet to be studied. We
      therefore investigated the impact of post-weaning isolation on socio-affective
      information processing as assessed by means of our established 50-kHz USV radial
      maze playback paradigm. We showed that post-weaning social isolation specifically
      affected the behavioral response to playback of pro-social 50-kHz but not alarm
      22-kHz USV. While group-housed rats showed the expected preference, i.e.,
      approach, toward 50-kHz USV, the response was even stronger in short-term
      isolated rats (i.e., 1 day), possibly due to a higher level of social motivation.
      In contrast, no approach was observed in long-term isolated rats (i.e., 4 weeks).
      Importantly, deficits in approach were reversed by peer-mediated re-socialization
      and could not be observed after post-adolescent social isolation, indicating a
      critical period for social development during adolescence. Together, these
      results highlight the importance of social experience for affiliative behavior,
      suggesting a critical involvement of play behavior on socio-affective information
      processing in rats. 

PMID- 25983683
TI  - The challenges and benefits of a genuine partnership between Music Therapy and
      Neuroscience: a dialog between scientist and therapist.
AB  - Collaborations between neuroscience and music therapy promise many mutual
      benefits given the different knowledge bases, experiences and specialist skills
      possessed by each discipline. Primarily, music therapists deliver music-based
      interventions on a daily basis with numerous populations; neuroscientists measure
      clinical changes in ways that provide an evidence base for progressing clinical
      care. Although recent developments suggest that partnerships between the two can
      produce positive outcomes for both fields, these collaborations are not
      considered mainstream. The following dialog between an experienced professional
      from each discipline explores the potential for collaboration, as well as the
      misconceptions that may be preventing further synergies from developing. 

PMID- 25983644
TI  - Production of [Formula: see text] and [Formula: see text] in proton-proton
      collisions at [Formula: see text] 7 TeV.
AB  - The production of the strange and double-strange baryon resonances ([Formula: see
      text], [Formula: see text]) has been measured at mid-rapidity ([Formula: see
      text][Formula: see text]) in proton-proton collisions at [Formula: see text]
      [Formula: see text] 7 TeV with the ALICE detector at the LHC. Transverse momentum
      spectra for inelastic collisions are compared to QCD-inspired models, which in
      general underpredict the data. A search for the [Formula: see text] pentaquark,
      decaying in the [Formula: see text] channel, has been carried out but no evidence
      is seen.

PMID- 25983682
TI  - Age-related striatal BOLD changes without changes in behavioral loss aversion.
AB  - Loss aversion (LA), the idea that negative valuations have a higher psychological
      impact than positive ones, is considered an important variable in consumer
      research. The literature on aging and behavior suggests older individuals may
      show more LA, although it is not clear if this is an effect of aging in general
      (as in the continuum from age 20 and 50 years), or of the state of older age
      (e.g., past age 65 years). We also have not yet identified the potential
      biological effects of aging on the neural processing of LA. In the current study
      we used a cohort of subjects with a 30 year range of ages, and performed whole
      brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens
      (VS/NAc) response during a passive viewing of affective faces with model-based
      fMRI analysis incorporating behavioral data from a validated approach/avoidance
      task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the
      VS/NAc being a central region for reward/aversion processing; (2) its activation
      to both positive and negative stimuli; (3) its reported involvement with tracking
      LA. LA from approach/avoidance to affective faces showed excellent fidelity to
      published measures of LA. Imaging results were then compared to the behavioral
      measure of LA using the same affective faces. Although there was no relationship
      between age and LA, we observed increasing neural differential sensitivity (NDS)
      of the VS/NAc to avoidance responses (negative valuations) relative to approach
      responses (positive valuations) with increasing age. These findings suggest that
      a central region for reward/aversion processing changes with age, and may require
      more activation to produce the same LA behavior as in younger individuals,
      consistent with the idea of neural efficiency observed with high IQ individuals
      showing less brain activation to complete the same task. 

PMID- 25983685
TI  - Sleep spindle alterations in patients with Parkinson's disease.
AB  - The aim of this study was to identify changes of sleep spindles (SS) in the EEG
      of patients with Parkinson's disease (PD). Five sleep experts manually identified
      SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched
      control subjects. Each SS was given a confidence score, and by using a group
      consensus rule, 901 SS were identified and characterized by their (1) duration,
      (2) oscillation frequency, (3) maximum peak-to-peak amplitude, (4) percent-to
      peak amplitude, and (5) density. Between-group comparisons were made for all SS
      characteristics computed, and significant changes for PD patients vs. control
      subjects were found for duration, oscillation frequency, maximum peak-to-peak
      amplitude and density. Specifically, SS density was lower, duration was longer,
      oscillation frequency slower and maximum peak-to-peak amplitude higher in
      patients vs. CONTROLS: We also computed inter-expert reliability in SS scoring
      and found a significantly lower reliability in scoring definite SS in patients
      when compared to controls. How neurodegeneration in PD could influence SS
      characteristics is discussed. We also note that the SS morphological changes
      observed here may affect automatic detection of SS in patients with PD or other
      neurodegenerative disorders (NDDs).

PMID- 25983684
TI  - Structural white matter changes in descending motor tracts correlate with
      improvements in motor impairment after undergoing a treatment course of tDCS and
      physical therapy.
AB  - Motor impairment after stroke has been related to the structural and functional
      integrity of corticospinal tracts including multisynaptic motor fibers and tracts
      such as the cortico-rubral-spinal and the cortico-tegmental-spinal tract.
      Furthermore, studies have shown that the concurrent use of transcranial direct
      current stimulation (tDCS) with peripheral sensorimotor activities can improve
      motor impairment. We examined microstructural effects of concurrent non-invasive
      bihemispheric stimulation and physical/occupational therapy for 10 days on the
      structural components of the CST as well as other descending motor tracts which
      will be referred to here as alternate motor fibers (aMF). In this pilot study,
      ten chronic patients with a uni-hemispheric stroke underwent Upper-Extremity Fugl
      Meyer assessments (UE-FM) and diffusion tensor imaging (DTI) for determining
      diffusivity measures such as fractional anisotropy (FA) before and after
      treatment in a section of the CST and aMF that spanned between the lower end of
      the internal capsule (below each patient's lesion) and the upper pons region on
      the affected and unaffected hemisphere. The treated group (tDCS + PT/OT) showed
      significant increases in the proportional UE-FM scores (+21%; SD 10%), while no
      significant changes were observed in an untreated comparison group. Significant
      increases in FA (+0.007; SD 0.0065) were found in the ipsilesional aMF in the
      treated group while no significant changes were found in the contralesional aMF,
      in either CST, or in any tracts in the untreated group. The FA changes in the
      ipsilesional aMF significantly correlated with the proportional change in the UE
      FM (r = 0.65; p < 0.05). The increase in FA might indicate an increase in motor
      fiber alignment, myelination, and overall fiber integrity. Crossed and uncrossed
      fibers from multiple cortical regions might be one reason why the aMF fiber
      system showed more plastic structural changes that correlate with motor
      improvements than the CST. 

PMID- 25983686
TI  - Spatial displacement of numbers on a vertical number line in spatial neglect.
AB  - Previous studies that investigated the association of numbers and space in humans
      came to contradictory conclusions about the spatial character of the mental
      number magnitude representation and about how it may be influenced by unilateral
      spatial neglect. The present study aimed to disentangle the debated influence of
      perceptual vs. representational aspects via explicit mapping of numbers onto
      space by applying the number line estimation paradigm with vertical orientation
      of stimulus lines. Thirty-five acute right-brain damaged stroke patients (6 with
      neglect) were asked to place two-digit numbers on vertically oriented lines with
      0 marked at the bottom and 100 at the top. In contrast to the expected, nearly
      linear mapping in the control patient group, patients with spatial neglect
      overestimated the position of numbers in the lower middle range. The results
      corroborate spatial characteristics of the number magnitude representation. In
      neglect patients, this representation seems to be biased towards the ipsilesional
      side, independent of the physical orientation of the task stimuli. 

PMID- 25983687
TI  - Too easy? The influence of task demands conveyed tacitly on prospective memory.
AB  - Previous research suggests that when intentions are encoded, participants
      establish an attention allocation policy based on their metacognitive beliefs
      about how demanding it will be to fulfill the prospective memory (PM) task. We
      investigated whether tacit PM demands can influence judgments about the cognitive
      effort required for success, and, as a result, affect ongoing task interference
      and PM performance. Participants performed a lexical decision task in which a PM
      task of responding to animal words was embedded. PM demands were tacitly
      manipulated by presenting participants with either typical or atypical animal
      exemplars at both instructions and practice (low vs. high tacit demands,
      respectively). Crucially, objective PM task demands were the same for all
      participants as PM targets were always atypical animals. Tacit demands affected
      participants' attention allocation policies such that task interference was
      greater for the high than low demands condition. Also, PM performance was reduced
      in the low relative to the high demands condition. Participants in the low
      demands condition who succeeded to the first target showed a subsequent increase
      in task interference, suggesting adjustment to the higher than expected demands.
      This study demonstrates that tacit information regarding the PM task can affect
      ongoing task processing as well as harm PM performance when actual demands are
      higher than expected. Furthermore, in line with the proposal that attention
      allocation is a dynamic and flexible process, we found evidence that PM task
      experience can trigger changes in ongoing task interference. 

PMID- 25983688
TI  - Prism adaptation and spatial neglect: the need for dose-finding studies.
AB  - Spatial neglect is a devastating disorder in 50-70% of right-brain stroke
      survivors, who have problems attending to, or making movements towards, left
      sided stimuli, and experience a high risk of chronic dependence. Prism adaptation
      is a promising treatment for neglect that involves brief, daily visuo-motor
      training sessions while wearing optical prisms. Its benefits extend to functional
      behaviors such as dressing, with effects lasting 6 months or longer. Because one
      to two sessions of prism adaptation induce adaptive changes in both spatial-motor
      behavior (Fortis et al., 2011) and brain function (Saj et al., 2013), it is
      possible stroke patients may benefit from treatment periods shorter than the
      standard, intensive protocol of ten sessions over two weeks-a protocol that is
      impractical for either US inpatient or outpatient rehabilitation. Demonstrating
      the effectiveness of a lower dose will maximize the availability of neglect
      treatment. We present preliminary data suggesting that four to six sessions of
      prism treatment may induce a large treatment effect, maintained three to four
      weeks post-treatment. We call for a systematic, randomized clinical trial to
      establish the minimal effective dose suitable for stroke intervention. 

PMID- 25983689
TI  - Disruption in proprioception from long-term thalamic deep brain stimulation: a
      pilot study.
AB  - Deep brain stimulation (DBS) is an excellent treatment for tremor and is
      generally thought to be reversible by turning off stimulation. For tremor, DBS is
      implanted in the ventrointermedius (Vim) nucleus of the thalamus, a region that
      relays proprioceptive information for movement sensation (kinaesthesia). Gait
      disturbances have been observed with bilateral Vim DBS, but the long-term effects
      on proprioceptive processing are unknown. We aimed to determine whether Vim DBS
      surgical implantation or stimulation leads to proprioceptive deficits in the
      upper limb. We assessed two groups of tremor subjects on measures of
      proprioception (kinaesthesia, position sense) and motor function using a robotic
      exoskeleton. In the first group (Surgery), we tested patients before and after
      implantation of Vim DBS, but before DBS was turned on to determine if
      proprioceptive deficits were inherent to tremor or caused by DBS implantation. In
      the second group (Stim), we tested subjects with chronically implanted Vim DBS ON
      and OFF stimulation. Compared to controls, there were no proprioceptive deficits
      before or after DBS implantation in the Surgery group. Surprisingly, those that
      received chronic long-term stimulation (LT-stim, 3-10 years) displayed
      significant proprioceptive deficits ON and OFF stimulation not present in
      subjects with chronic short-term stimulation (ST-stim, 0.5-2 years). LT-stim had
      significantly larger variability and reduced workspace area during the position
      sense assessment. During the kinesthetic assessment, LT-stim made significantly
      larger directional errors and consistently underestimated the speed of the robot,
      despite generating normal movement speeds during motor assessment. Chronic long
      term Vim DBS may potentially disrupt proprioceptive processing, possibly inducing
      irreversible plasticity in the Vim nucleus and/or its network connections. Our
      findings in the upper limb may help explain some of the gait disturbances seen by
      others following Vim DBS. 

PMID- 25983690
TI  - Simultaneous learning and filtering without delusions: a Bayes-optimal
      combination of Predictive Inference and Adaptive Filtering.
AB  - Predictive coding appears to be one of the fundamental working principles of
      brain processing. Amongst other aspects, brains often predict the sensory
      consequences of their own actions. Predictive coding resembles Kalman filtering,
      where incoming sensory information is filtered to produce prediction errors for
      subsequent adaptation and learning. However, to generate prediction errors given
      motor commands, a suitable temporal forward model is required to generate
      predictions. While in engineering applications, it is usually assumed that this
      forward model is known, the brain has to learn it. When filtering sensory input
      and learning from the residual signal in parallel, a fundamental problem arises:
      the system can enter a delusional loop when filtering the sensory information
      using an overly trusted forward model. In this case, learning stalls before
      accurate convergence because uncertainty about the forward model is not properly
      accommodated. We present a Bayes-optimal solution to this generic and pernicious
      problem for the case of linear forward models, which we call Predictive Inference
      and Adaptive Filtering (PIAF). PIAF filters incoming sensory information and
      learns the forward model simultaneously. We show that PIAF is formally related to
      Kalman filtering and to the Recursive Least Squares linear approximation method,
      but combines these procedures in a Bayes optimal fashion. Numerical evaluations
      confirm that the delusional loop is precluded and that the learning of the
      forward model is more than 10-times faster when compared to a naive combination
      of Kalman filtering and Recursive Least Squares. 

PMID- 25983691
TI  - miR-155 is involved in Alzheimer's disease by regulating T lymphocyte function.
AB  - Alzheimer's disease (AD) is considered the most common cause of sporadic
      dementia. In AD, adaptive and innate immune responses play a crucial role in
      clearance of amyloid beta and maintenance of cognitive functions. In addition to
      other changes in the immune system, AD alters the T-cell responses that affect
      activation of glial cells, neuronal cells, macrophages, and secretion of pro
      inflammatory cytokines. These changes in the immune system influence AD
      pathogenesis. Micro-RNA (miRNA)-155 is a multifunctional miRNA with a distinct
      expression profile. It is involved in diverse physiological and pathological
      mechanisms, such as immunity and inflammation. Recent studies indicate that miR
      155 regulates T-cell functions during inflammation. In this article, we summarize
      recent studies describing the therapeutic potential of miR-155 via regulation of
      T cells in AD. Further, we propose that regulation of miR-155 might be a new
      protective approach against AD pathogenesis. 

PMID- 25983692
TI  - Editorial: "From brain to body: the impact of nervous system declines on muscle
      performance in aging".

PMID- 25983694
TI  - Impact of a novel protein meal on the gastrointestinal microbiota and the host
      transcriptome of larval zebrafish Danio rerio.
AB  - Larval zebrafish was subjected to a methodological exploration of the
      gastrointestinal microbiota and transcriptome. Assessed was the impact of two
      dietary inclusion levels of a novel protein meal (NPM) of animal origin (ragworm
      Nereis virens) on the gastrointestinal tract (GIT). Microbial development was
      assessed over the first 21 days post egg fertilization (dpf) through 16S rRNA
      gene-based microbial composition profiling by pyrosequencing. Differentially
      expressed genes in the GIT were demonstrated at 21 dpf by whole transcriptome
      sequencing (mRNAseq). Larval zebrafish showed rapid temporal changes in microbial
      colonization but domination occurred by one to three bacterial species generally
      belonging to Proteobacteria and Firmicutes. The high iron content of NPM may have
      led to an increased relative abundance of bacteria that were related to potential
      pathogens and bacteria with an increased iron metabolism. Functional
      classification of the 328 differentially expressed genes indicated that the GIT
      of larvae fed at higher NPM level was more active in transmembrane ion transport
      and protein synthesis. mRNAseq analysis did not reveal a major activation of
      genes involved in the immune response or indicating differences in iron uptake
      and homeostasis in zebrafish fed at the high inclusion level of NPM. 

PMID- 25983693
TI  - The study of homology between tumor progression genes and members of retroviridae
      as a tool to predict target-directed therapy failure.
AB  - Oncogenes are the primary candidates for target-directed therapy, given that they
      are involved directly in the progression and resistance of tumors. However, the
      appearance of point mutations can hinder the treatment of patients with these new
      molecules, raising costs and the need to development new analogs that target the
      novel mutations. Based on an analysis of homologies, the present study discusses
      the possibility of predicting the failure of a protein as a pharmacological
      target, due to its similarities with retrovirus sequences, which have extremely
      high mutation rates. This analysis was based on the molecular evidence available
      in the literature, and widely-used and well-established PSI-BLAST, with two
      iterations and maximum of 500 aligned sequences. The possibility of predicting
      which newly-discovered genes involved in tumor progression would likely result in
      the failure of targeted therapy, using free, simple and automated bioinformatics
      tools, could provide substantial savings in the time and financial resources
      needed for long-term drug development. 

PMID- 25983695
TI  - Improved Sleep in Military Personnel is Associated with Changes in the Expression
      of Inflammatory Genes and Improvement in Depression Symptoms.
AB  - STUDY OBJECTIVES: Sleep disturbances are common in military personnel and are
      associated with increased risk for psychiatric morbidity, including posttraumatic
      stress disorder (PTSD) and depression, as well as inflammation. Improved sleep
      quality is linked to reductions in inflammatory bio-markers; however, the
      underlying mechanisms remain elusive. METHODS: In this study, we examine whole
      genome expression changes related to improved sleep in 68 military personnel
      diagnosed with insomnia. Subjects were classified into the following groups and
      then compared: improved sleep (n = 46), or non-improved sleep (n = 22) following
      three months of standard of care treatment for insomnia. Within subject
      differential expression was determined from microarray data using the Partek
      Genomics Suite analysis program and the ingenuity pathway analysis (IPA) was used
      to determine key regulators of observed expression changes. Changes in symptoms
      of depression and PTSD were also compared. RESULTS: At baseline, both groups were
      similar in demographics, clinical characteristics, and gene-expression profiles.
      The microarray data revealed that 217 coding genes were differentially expressed
      at the follow-up-period compared to baseline in the participants with improved
      sleep. Expression of inflammatory cytokines were reduced including IL-1beta, IL
      6, IL-8, and IL-13, with fold changes ranging from -3.19 to -2.1, and there were
      increases in the expression of inflammatory regulatory genes including toll-like
      receptors 1, 4, 7, and 8 in the improved sleep group. IPA revealed six gene
      networks, including ubiquitin, which was a major regulator in these gene
      expression changes. The improved sleep group also had a significant reduction in
      the severity of depressive symptoms. CONCLUSION: Interventions that restore sleep
      likely reduce the expression of inflammatory genes, which relate to ubiquitin
      genes and relate to reductions in depressive symptoms.

PMID- 25983696
TI  - Explaining interindividual differences in toddlers' collaboration with unfamiliar
      peers: individual, dyadic, and social factors.
AB  - During their third year of life, toddlers become increasingly skillful at
      coordinating their actions with peer partners and they form joint commitments in
      collaborative situations. However, little effort has been made to explain
      interindividual differences in collaboration among toddlers. Therefore, we
      examined the relative influence of distinct individual, dyadic, and social
      factors on toddlers' collaborative activities (i.e., level of coordination and
      preference for joint activity) in joint problem-solving situations with
      unfamiliar peer partners (n = 23 dyads aged M = 35.7 months). We analyzed the
      dyadic nonindependent data with mixed models. Results indicated that mothers'
      expectations regarding their children's social behaviors significantly predicted
      toddlers' level of coordination. Furthermore, the models revealed that toddlers'
      positive mutual experiences with the unfamiliar partner assessed during an
      initial free play period (Phase 1) and their level of coordination in an
      obligatory collaboration task (Phase 2) promoted toddlers' preference for joint
      activity in a subsequent optional collaboration task (Phase 3). In contrast,
      children's mastery motivation and shyness conflicted with their collaborative
      efforts. We discuss the role of parents' socialization goals in toddlers'
      development toward becoming active collaborators and discuss possible mechanisms
      underlying the differences in toddlers' commitment to joint activities, namely
      social preferences and the trust in reliable cooperation partners. 

PMID- 25983698
TI  - The enhanced Aussie Optimism Positive Thinking Skills Program: The relationship
      between internalizing symptoms and family functioning in children aged 9-11 years
      old.
AB  - The family context plays a critical role in the health of the child. This was the
      first study to examine the usefulness of the General Functioning subscale of the
      Family Assessment Device (FAD-GF) in assessing family functioning and its
      relationship to internalizing symptoms in school-aged children aged between 9 and
      11 years of age. Eight hundred and forty-seven year 4 and 5 students from 13
      schools (607 intervention students, and 240 control students) participated in the
      Aussie Optimism Positive Thinking Skills Program (AO-PTS) - a universal school
      based program targeting internalizing symptoms. Students rated how 'healthy' they
      perceived their family to be at pre-test and at 6-months follow-up. Although some
      aspects of validity and reliability could be improved, results indicated that
      perceptions of family functioning at pre-test were predictive of internalizing
      symptoms at the 6-months follow-up. The FAD-GF therefore showed promise as a
      potential measure of family functioning for children as young as 9 years old.
      Regardless of children's pre-test levels of perceived family functioning, no
      intervention effects were found on the anxiety and depression scales; this
      finding suggests that child perceptions of family functioning may act as a
      general protective factor against internalizing symptomology. 

PMID- 25983700
TI  - The uses and abuses of the coherence - correspondence distinction.
AB  - Kenneth Hammond introduced a distinction between coherence and correspondence
      criteria of rationality as a tool in the study of judgment and decision-making.
      This distinction has been widely used in the field. Yet, as this paper seeks to
      show, the relevant notions of coherence and correspondence have been
      progressively considered to be too narrow and have undergone non-trivial
      conceptual changes since their original introduction. I try to show, first, that
      the proliferation of conceptualizations of coherence and correspondence has
      created confusion in the literature and that appealing to such notions has not
      helped to elucidate discussions over the nature of rational judgment and decision
      making. Nevertheless, I also argue for a reframing of the debate. In fact, what
      seems to underlie several contemporary appeals to the notions of coherence and
      correspondence is best explained in terms of a contrast between what I call rule
      based and goal-based rationality. Whilst these categories do need further
      refinement, they do seem to be useful for organizing and understanding research
      on rational judgment and decision-making. 

PMID- 25983697
TI  - Disentangling interoception: insights from focal strokes affecting the perception
      of external and internal milieus.
AB  - Interoception is the moment-to-moment sensing of the physiological condition of
      the body. The multimodal sources of interoception can be classified into two
      different streams of afferents: an internal pathway of signals arising from core
      structures (i.e., heart, blood vessels, and bronchi) and an external pathway of
      body-mapped sensations (i.e., chemosensation and pain) arising from peripersonal
      space. This study examines differential processing along these streams within the
      insular cortex (IC) and their subcortical tracts connecting frontotemporal
      networks. Two rare patients presenting focal lesions of the IC (insular lesion,
      IL) or its subcortical tracts (subcortical lesion, SL) were tested. Internally
      generated interoceptive streams were assessed through a heartbeat detection (HBD)
      task, while those externally triggered were tapped via taste, smell, and pain
      recognition tasks. A differential pattern was observed. The IC patient showed
      impaired internal signal processing while the SL patient exhibited external
      perception deficits. Such selective deficits remained even when comparing each
      patient with a group of healthy controls and a group of brain-damaged patients.
      These outcomes suggest the existence of distinguishable interoceptive streams.
      Results are discussed in relation with neuroanatomical substrates, involving a
      fronto-insulo-temporal network for interoceptive and cognitive contextual
      integration. 

PMID- 25983699
TI  - What you learn is more than what you see: what can sequencing effects tell us
      about inductive category learning?
AB  - Inductive category learning takes place across time. As such, it is not
      surprising that the sequence in which information is studied has an impact in
      what is learned and how efficient learning is. In this paper we review research
      on different learning sequences and how this impacts learning. We analyze
      different aspects of interleaved (frequent alternation between categories during
      study) and blocked study (infrequent alternation between categories during study)
      that might explain how and when one sequence of study results in improved
      learning. While these different sequences of study differ in the amount of
      temporal spacing and temporal juxtaposition between items of different
      categories, these aspects do not seem to account for the majority of the results
      available in the literature. However, differences in the type of category being
      studied and the duration of the retention interval between study and test may
      play an important role. We conclude that there is no single aspect that is able
      to account for all the evidence available. Understanding learning as a process of
      sequential comparisons in time and how different sequences fundamentally alter
      the statistics of this experience offers a promising framework for understanding
      sequencing effects in category learning. We use this framework to present novel
      predictions and hypotheses for future research on sequencing effects in inductive
      category learning. 

PMID- 25983701
TI  - Excess success for three related papers on racial bias.
AB  - Three related articles reported that racial bias altered perceptual experience
      and influenced decision-making. These findings have been applied to training
      programs for law enforcement, and elsewhere, to mitigate racial bias. However, a
      statistical analysis of each of the three articles finds that the reported
      experimental results should be rare, even if the theoretical ideas were correct.
      The analysis estimates that the probability of the reported experimental success
      for the articles is 0.003, 0.048, and 0.070, respectively. These low
      probabilities suggest that similar future work is unlikely to produce as
      successful outcomes and indicates that readers should be skeptical about the
      validity of the reported findings and their theoretical implications. The
      reported findings should not be used to guide policies related to racial bias,
      and new experimental work is needed to judge the merit of the theoretical ideas. 

PMID- 25983702
TI  - Emotional responses to Hindustani raga music: the role of musical structure.
AB  - In Indian classical music, ragas constitute specific combinations of tonic
      intervals potentially capable of evoking distinct emotions. A raga composition is
      typically presented in two modes, namely, alaap and gat. Alaap is the note by
      note delineation of a raga bound by a slow tempo, but not bound by a rhythmic
      cycle. Gat on the other hand is rendered at a faster tempo and follows a rhythmic
      cycle. Our primary objective was to (1) discriminate the emotions experienced
      across alaap and gat of ragas, (2) investigate the association of tonic
      intervals, tempo and rhythmic regularity with emotional response. 122
      participants rated their experienced emotion across alaap and gat of 12 ragas.
      Analysis of the emotional responses revealed that (1) ragas elicit distinct
      emotions across the two presentation modes, and (2) specific tonic intervals are
      robust predictors of emotional response. Specifically, our results showed that
      the 'minor second' is a direct predictor of negative valence. (3) Tonality
      determines the emotion experienced for a raga where as rhythmic regularity and
      tempo modulate levels of arousal. Our findings provide new insights into the
      emotional response to Indian ragas and the impact of tempo, rhythmic regularity
      and tonality on it. 

PMID- 25983703
TI  - Improving working memory in children with low language abilities.
AB  - This study investigated whether working memory training is effective in enhancing
      verbal memory in children with low language abilities (LLA). Cogmed Working
      Memory Training was completed by a community sample of children aged 8-11 years
      with LLA and a comparison group with matched non-verbal abilities and age-typical
      language performance. Short-term memory (STM), working memory, language, and IQ
      were assessed before and after training. Significant and equivalent post-training
      gains were found in visuo-spatial short-term memory in both groups. Exploratory
      analyses across the sample established that low verbal IQ scores were strongly
      and highly specifically associated with greater gains in verbal STM, and that
      children with higher verbal IQs made greater gains in visuo-spatial short-term
      memory following training. This provides preliminary evidence that intensive
      working memory training may be effective for enhancing the weakest aspects of STM
      in children with low verbal abilities, and may also be of value in developing
      compensatory strategies. 

PMID- 25983704
TI  - Words putting pain in motion: the generalization of pain-related fear within an
      artificial stimulus category.
AB  - Patients with chronic pain are often fearful of movements that never featured in
      painful episodes. This study examined whether a neutral movement's conceptual
      relationship with pain-relevant stimuli could precipitate pain-related fear; a
      process known as symbolic generalization. As a secondary objective, we also
      compared experiential and verbal fear learning in the generalization of pain
      related fear. We conducted an experimental study with 80 healthy participants who
      were recruited through an online experimental management system (M age = 23.04
      years, SD = 6.80 years). First, two artificial categories were established
      wherein nonsense words and joystick arm movements were equivalent. Using a
      between-groups design, nonsense words from one category were paired with either
      an electrocutaneous stimulus (pain-US) or threatening information, while nonsense
      words from the other category were paired with no pain-US or safety information.
      During a final testing phase, participants were prompted to perform specific
      joystick arm movements that were never followed by a pain-US, although they were
      informed that it could occur. The results showed that movements equivalent to the
      pain-relevant nonsense words evoked heightened pain-related fear as measured by
      pain-US expectancy, fear of pain, and unpleasantness ratings. Also, experience
      with the pain-US evinced stronger acquisition and generalization compared to
      experience with threatening information. The clinical importance and theoretical
      implications of these findings are discussed. 

PMID- 25983705
TI  - The development of memory maintenance strategies: training cumulative rehearsal
      and interactive imagery in children aged between 5 and 9.
AB  - The current study explored the extent to which children above and below the age
      of 7 years are able to benefit from either training in cumulative rehearsal or in
      the use of interactive imagery when carrying out working memory tasks. Twenty
      four 5- to 6-year-olds nd 24 8- to 9-year olds were each assigned to one of three
      training groups who either received cumulative rehearsal, interactive imagery, or
      passive labeling training. Participants' ability to maintain material during a
      filled delay was then assessed, and the nature of the distraction that was
      imposed during this delay was varied to shed further light on the mechanisms that
      individuals used to maintain the memoranda in working memory in the face of this
      distraction. The results suggest that the rehearsal training employed here did
      improve recall by virtue of encouraging rehearsal strategies, in a way that was
      not observed among participants receiving interactive imagery training. The fact
      that these effects were not mediated by age group counts against the view that
      younger individuals are either unable to rehearse, or show impoverished verbal
      serial recall because they do not spontaneously engage in rehearsal. 

PMID- 25983706
TI  - Improving executive function in childhood: evaluation of a training intervention
      for 5-year-old children.
AB  - Executive function (EF) refers to a set of higher order cognitive processes that
      control and modulate cognition under continuously changing and multiple task
      demands. EF plays a central role in early childhood, is associated and predictive
      of important cognitive achievements and has been recognized as a significant
      aspect of school readiness. This study examines the efficacy of a group based
      intervention for 5-year-old children that focuses on basic components of EF
      (working memory, inhibitory control, cognitive flexibility). The intervention
      included 12 sessions, lasted 1 month and used low-cost materials. Seventy-five
      children took part in the study. The results indicate that the children who
      attended the intervention outperformed controls in simple and more complex EF
      tasks. Specifically, these children exhibited increased abilities to delay
      gratification, to control on-going responses, to process and update information,
      and to manage high cognitive conflict. These results suggest the possibility that
      this intervention, which may be easily implemented in educational services, can
      promote EF during preschool period before the entrance in primary school. 

PMID- 25983707
TI  - The Early Identity Exploration Scale-a measure of initial exploration in breadth
      during early adolescence.
AB  - The existing models and measurement instruments concerning identity appear to
      primarily focus on adolescence and early adulthood, and studies extending
      identity research to younger stages of life are scarce. There has been a
      particular lack of instruments measuring the early stages of identity formation,
      especially the process of exploration, which has been portrayed as a central
      process during this particular period of life. Our aim is to help fill the gap in
      the literature and facilitate further studies of the exploration process by
      providing an appropriate instrument to measure exploration in breadth during
      early adolescence. As a coherent and mature sense of identity is closely
      associated with psychosocial well-being, an effective identity exploration scale
      will enable researchers to assess the predictors of young adolescents' well
      being. We propose a model of identity exploration domains based on the literature
      and considering 12 exploration domains: physical appearance, free time, family,
      work, boyfriend-girlfriend relationships, own opinion formation, perception of
      own place in the life cycle, self-reflection, future, future family, outlook on
      life, and attitude toward rules. The study was conducted on a group of N = 454
      adolescents (50% males, M age = 13.04, SD = 0.98). Both reliability and
      structural validity, as verified by confirmatory factor analysis were
      satisfactory. The instrument is invariant across gender groups at the scalar
      level of measurement invariance. 

PMID- 25983709
TI  - Predicting self-reported research misconduct and questionable research practices
      in university students using an augmented Theory of Planned Behavior.
AB  - This study examined the utility of the Theory of Planned Behavior model,
      augmented by descriptive norms and justifications, for predicting self-reported
      research misconduct and questionable research practices in university students. A
      convenience sample of 205 research active Western Australian university students
      (47 male, 158 female, ages 18-53 years, M = 22, SD = 4.78) completed an online
      survey. There was a low level of engagement in research misconduct, with
      approximately one in seven students reporting data fabrication and one in eight
      data falsification. Path analysis and model testing in LISREL supported a
      parsimonious two step mediation model, providing good fit to the data. After
      controlling for social desirability, the effect of attitudes, subjective norms,
      descriptive norms and perceived behavioral control on student engagement in
      research misconduct and questionable research practices was mediated by
      justifications and then intention. This revised augmented model accounted for a
      substantial 40.8% of the variance in student engagement in research misconduct
      and questionable research practices, demonstrating its predictive utility. The
      model can be used to target interventions aimed at reducing student engagement in
      research misconduct and questionable research practices. 

PMID- 25983708
TI  - Content analysis of 4 to 8 year-old children's dream reports.
AB  - The role of dreaming in childhood and in adulthood are still equally enigmatic
      fields yet to be fully explored. However, while there is a consensus at least
      about the typical content and formal characteristics of adult dream reports,
      these features are still a matter of debate in the case of young children.
      Longitudinal developmental laboratory studies concluded that preschoolers' dreams
      usually depict static images about mostly animals and body states of the dreamer
      but they basically lack the active representation of the self, human characters,
      social interactions, dream emotions and motion imagery. Due to methodological
      arguments these results became the reference points in the literature of
      developmental dream research, in spite of the significantly different results of
      numerous recent and relevant studies using extra-laboratory settings. This study
      aims to establish a methodologically well-controlled and valid way to collect
      children's dreams for a representative period of time in a familiar home setting
      to serve as a comparison to the laboratory method. Pre trained parents acted as
      interviewers in the course of a 6 week-period of dream collection upon morning
      awakenings. Our results suggest that even preschoolers are likely to represent
      their own self in an active role (70%) in their mostly kinematic (82%) dream
      narratives. Their dream reports contain more human, than animal characters (70
      and 7% of all dream characters respectively), and social interactions, self
      initiated actions, and emotions are usual part of these dreams. These results are
      rather similar to those of recent extra-laboratory studies, suggesting that
      methodological issues may strongly interfere with research outcomes especially in
      the case of preschoolers' dream narratives. We suggest that nighttime awakenings
      in the laboratory setting could be crucial in understanding the contradictory
      results of dream studies in case of young children. 

PMID- 25983710
TI  - Commentary: Cafeteria diet impairs expression of sensory-specific satiety and
      stimulus-outcome learning.

PMID- 25983711
TI  - Communicating numeric quantities in context: implications for decision science
      and rationality claims.

PMID- 25983712
TI  - Gollin's (1965) levels-by-levels approach: the importance of manipulating the
      task dimension when assessing age-related changes and individual differences in
      decision making.

PMID- 25983713
TI  - Joint attention for stimuli on the hands: ownership matters.
AB  - The visual system treats the space near the hands with unique, action-related
      priorities. For example, attention orients slowly to stimuli on the hands (Taylor
      and Witt, 2014). In this article, we asked whether jointly attended hands are
      attended in the same way. Specifically, we examined whether ownership over the
      hand mattered: do we attend to our hands and the hands of others in the same way?
      Pairs of participants performed a spatial cueing task with stimuli that could be
      projected onto one partner's hands or on a control surface. Results show delayed
      orienting of attention to targets appearing on the hands, but only for the owner
      of the hands. For an observer, others' hands are like any other surface. This
      result emphasizes the importance of ownership for hand-based effects on vision,
      and in doing so, is inconsistent with some expectations of the joint action
      literature. 

PMID- 25983714
TI  - Differential impact of affective and cognitive attributes on preference under
      deliberation and distraction.
AB  - Two experiments were designed to test the hypothesis that affective information
      looms relatively larger than cognitive information when individuals are
      distracted for a period of time compared to when they engage in deliberative
      thinking. In two studies, participants were presented with information about 4
      decision alternatives: An affective alternative that scored high on affective
      attributes but low on cognitive attributes, a cognitive alternative with the
      opposite trade-off, and two fillers. They were then asked to indicate their
      attitudes toward each of four decision alternatives either immediately, after a
      period of deliberation, or after a period of distraction. The results of both
      experiments demonstrated that participants significantly preferred the affective
      alternative to the cognitive alternative after distraction, but not after
      deliberation. The implications for understanding when and how unconscious thought
      may lead to better decisions are being discussed. 

PMID- 25983715
TI  - Heartfelt empathy? No association between interoceptive awareness, questionnaire
      measures of empathy, reading the mind in the eyes task or the director task.
AB  - Interoception, defined as afferent information arising from within the body, is
      the basis of all emotional experience and underpins the 'self.' However, people
      vary in the extent to which interoceptive signals reach awareness. This trait
      modulates both their experience of emotion and their ability to distinguish
      'self' from 'other' in multisensory contexts. The experience of emotion and the
      degree of self/other distinction or overlap are similarly fundamental to empathy,
      which is an umbrella term comprising affect sharing, empathic concern and
      perspective-taking (PT). A link has therefore often been assumed between
      interoceptive awareness (IA) and empathy despite a lack of clear evidence. To
      test the hypothesis that individual differences in both traits should correlate,
      we measured IA in four experiments, using a well-validated heartbeat perception
      task, and compared this with scores on several tests that relate to various
      aspects of empathy. We firstly measured scores on the Index of Interpersonal
      Reactivity and secondly on the Questionnaire of Cognitive and Affective Empathy.
      Thirdly, because the 'simulationist' account assumes that affect sharing is
      involved in recognizing emotion, we employed the 'Reading the Mind in the Eyes
      Task' for the recognition of facial expressions. Contrary to expectation, we
      found no significant relationships between IA and any aspect of these measures.
      This striking lack of direct links has important consequences for hypotheses
      about the extent to which empathy is necessarily embodied. Finally, to assess
      cognitive PT ability, which specifically requires self/other distinction, we used
      the 'Director Task' but found no relationship. We conclude that the abilities
      that make up empathy are potentially related to IA in a variety of conflicting
      ways, such that a direct association between IA and various components of empathy
      has yet to be established. 

PMID- 25983716
TI  - Striking a balance: analyzing unbalanced event-related potential data.

PMID- 25983717
TI  - Complementary actions.
AB  - Complementary colors are color pairs which, when combined in the right
      proportions, produce white or black. Complementary actions refer here to forms of
      social interaction wherein individuals adapt their joint actions according to a
      common aim. Notably, complementary actions are incongruent actions. But being
      incongruent is not sufficient to be complementary (i.e., to complete the action
      of another person). Successful complementary interactions are founded on the
      abilities: (i) to simulate another person's movements, (ii) to predict another
      person's future action/s, (iii) to produce an appropriate incongruent response
      which differ, while interacting, with observed ones, and (iv) to complete the
      social interaction by integrating the predicted effects of one's own action with
      those of another person. This definition clearly alludes to the functional
      importance of complementary actions in the perception-action cycle and prompts us
      to scrutinize what is taking place behind the scenes. Preliminary data on this
      topic have been provided by recent cutting-edge studies utilizing different
      research methods. This mini-review aims to provide an up-to-date overview of the
      processes and the specific activations underlying complementary actions. 

PMID- 25983718
TI  - Contrasting motivational orientation and evaluative coding accounts: on the need
      to differentiate the effectors of approach/avoidance responses.
AB  - Several emotion theorists suggest that valenced stimuli automatically trigger
      motivational orientations and thereby facilitate corresponding behavior. Positive
      stimuli were thought to activate approach motivational circuits which in turn
      primed approach-related behavioral tendencies whereas negative stimuli were
      supposed to activate avoidance motivational circuits so that avoidance-related
      behavioral tendencies were primed (motivational orientation account). However,
      recent research suggests that typically observed affective stimulus-response
      compatibility phenomena might be entirely explained in terms of theories
      accounting for mechanisms of general action control instead of assuming
      motivational orientations to mediate the effects (evaluative coding account). In
      what follows, we explore to what extent this notion is applicable. We present
      literature suggesting that evaluative coding mechanisms indeed influence a wide
      variety of affective stimulus-response compatibility phenomena. However, the
      evaluative coding account does not seem to be sufficient to explain affective S-R
      compatibility effects. Instead, several studies provide clear evidence in favor
      of the motivational orientation account that seems to operate independently of
      evaluative coding mechanisms. Implications for theoretical developments and
      future research designs are discussed. 

PMID- 25983719
TI  - Remembering donald f. Steiner.

PMID- 25983720
TI  - Ascertaining the relationship between Salmonella Typhimurium and Salmonella
      4,[5],12:i:- by MLVA and inferring the sources of human salmonellosis due to the
      two serovars in Italy.
AB  - The current picture of human salmonellosis shows Salmonella Typhimurium and S.
      4,[5],12:i:- as the most common serovars in Italy. The aims of this study were to
      investigate the genetic relationship between these serovars, as well as to test
      the possibility of inferring sources of human salmonellosis due to S. Typhimurium
      and S. 4,[5],12:i:- by using multilocus variable-number tandem repeat analysis
      (MLVA) subtyping data. Single isolates from 268 human sporadic cases and 325
      veterinary isolates (from pig, cattle, chicken, and turkey) collected over the
      period 2009-2011 were typed by MLVA, and the similarities of MLVA profiles were
      investigated using different analytical approaches. Results showed that isolates
      of S. 4,[5],12:i:- were more clonal compared to S. Typhimurium and that clones of
      both serovars from different non-human sources were very close to those which
      were responsible for human infections, suggesting that source attribution by MLVA
      typing should be possible. However, using the Asymmetric Island Model it was not
      possible to obtain a confident ranking of sources responsible for human
      infections based on MLVA profiles. The source assignments provided by the model
      could have been jeopardized by the high heterogeneity found within each source
      and the negligible divergence between sources as well as by the limited source
      data available, especially for some species. 

PMID- 25983721
TI  - Molecular epidemiology of Methicillin-resistant Staphylococcus aureus in Africa:
      a systematic review.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious
      global problem, with considerable impact on patients and substantial health care
      costs. This systematic review provides an overview on the clonal diversity of
      MRSA, as well as the prevalence of Panton-Valentine leukocidin (PVL)-positive
      MRSA in Africa. A search on the molecular characterization of MRSA in Africa was
      conducted by two authors using predefined terms. We screened for articles
      published in English and French through to October 2014 from five electronic
      databases. A total of 57 eligible studies were identified. Thirty-four reports
      from 15 countries provided adequate genotyping data. CC5 is the predominant
      clonal complex in the healthcare setting in Africa. The hospital-associated MRSA
      ST239/ST241-III [3A] was identified in nine African countries. This clone was
      also described with SCCmec type IV [2B] in Algeria and Nigeria, and type V [5C]
      in Niger. In Africa, the European ST80-IV [2B] clone was limited to Algeria,
      Egypt and Tunisia. The clonal types ST22-IV [2B], ST36-II [2A], and ST612-IV [2B]
      were only reported in South Africa. No clear distinctions were observed between
      MRSA responsible for hospital and community infections. The community clones ST8
      IV [2B] and ST88-IV [2B] were reported both in the hospital and community
      settings in Angola, Cameroon, Gabon, Ghana, Madagascar, Nigeria, and Sao Tome and
      Principe. The proportion of PVL-positive MRSA carriage and/or infections ranged
      from 0.3 to 100% in humans. A number of pandemic clones were identified in
      Africa. Moreover, some MRSA clones are limited to specific countries or regions.
      We strongly advocate for more surveillance studies on MRSA in Africa. 

PMID- 25983722
TI  - Reconstructing rare soil microbial genomes using in situ enrichments and
      metagenomics.
AB  - Despite extensive direct sequencing efforts and advanced analytical tools,
      reconstructing microbial genomes from soil using metagenomics have been
      challenging due to the tremendous diversity and relatively uniform distribution
      of genomes found in this system. Here we used enrichment techniques in an attempt
      to decrease the complexity of a soil microbiome prior to sequencing by submitting
      it to a range of physical and chemical stresses in 23 separate microcosms for 4
      months. The metagenomic analysis of these microcosms at the end of the treatment
      yielded 540 Mb of assembly using standard de novo assembly techniques (a total of
      559,555 genes and 29,176 functions), from which we could recover novel bacterial
      genomes, plasmids and phages. The recovered genomes belonged to Leifsonia (n =
      2), Rhodanobacter (n = 5), Acidobacteria (n = 2), Sporolactobacillus (n = 2,
      novel nitrogen fixing taxon), Ktedonobacter (n = 1, second representative of the
      family Ktedonobacteraceae), Streptomyces (n = 3, novel polyketide synthase
      modules), and Burkholderia (n = 2, includes mega-plasmids conferring mercury
      resistance). Assembled genomes averaged to 5.9 Mb, with relative abundances
      ranging from rare (<0.0001%) to relatively abundant (>0.01%) in the original soil
      microbiome. Furthermore, we detected them in samples collected from
      geographically distant locations, particularly more in temperate soils compared
      to samples originating from high-latitude soils and deserts. To the best of our
      knowledge, this study is the first successful attempt to assemble multiple
      bacterial genomes directly from a soil sample. Our findings demonstrate that
      developing pertinent enrichment conditions can stimulate environmental genomic
      discoveries that would have been impossible to achieve with canonical approaches
      that focus solely upon post-sequencing data treatment. 

PMID- 25983724
TI  - Diffusion of solutes inside bacterial colonies immobilized in model cheese
      depends on their physicochemical properties: a time-lapse microscopy study.
AB  - During cheese processing and ripening, bacteria develop as colonies. Substrates
      and metabolites must then diffuse either from or into the colonies. Exploring how
      the inner cells of the colony access the substrates or get rid of the products
      leads to study the diffusion of solutes inside bacterial colonies immobilized in
      cheese. Diffusion limitations of substrates within the bacterial colony could
      lead to starvation for the cells in the center of the colony. This study aimed at
      better understands ripening at the colony level, by investigating how diffusion
      phenomena inside colonies vary depending on both the physicochemical properties
      of the solutes and Lactococcus lactis strain. Dextrans (4, 70, and 155 kDa) and
      milk proteins (BSA, lactoferrin and alphaS1-casein) of different sizes and
      physicochemical properties were chosen as model of diffusing solutes, and two L.
      lactis strains presenting different surface properties were immobilized as
      colonies in a model cheese. Diffusion of solutes inside and around colonies was
      experimentally followed by time-lapse confocal microscopy. Dextran solutes
      diffused inside both lactococci colonies with a non-significantly different
      effective diffusion coefficient, which depended mainly on size of the solute.
      However, whereas flexible and neutral hydrophilic polymers such as dextran can
      diffuse inside colonies whatever its size, none of the three proteins
      investigated in this study could penetrate inside lactococci colonies. Therefore,
      the diffusion behavior of macromolecules through bacterial colonies immobilized
      in a model cheese did not only depends on the size of the diffusing solutes, but
      also and mainly on their physicochemical properties. Milk caseins are probably
      first hydrolyzed by the cell wall proteases of L. lactis and/or other proteases
      present in the cheese, and then the generated peptides diffuse inside colonies to
      be further metabolized into smaller peptides and amino acids by all the cells
      located inside the colonies. 

PMID- 25983723
TI  - Distinct microbial populations are tightly linked to the profile of dissolved
      iron in the methanic sediments of the Helgoland mud area, North Sea.
AB  - Iron reduction in subseafloor sulfate-depleted and methane-rich marine sediments
      is currently a subject of interest in subsurface geomicrobiology. While iron
      reduction and microorganisms involved have been well studied in marine surface
      sediments, little is known about microorganisms responsible for iron reduction in
      deep methanic sediments. Here, we used quantitative PCR-based 16S rRNA gene copy
      numbers and pyrosequencing-based relative abundances of bacteria and archaea to
      investigate covariance between distinct microbial populations and specific
      geochemical profiles in the top 5 m of sediment cores from the Helgoland mud
      area, North Sea. We found that gene copy numbers of bacteria and archaea were
      specifically higher around the peak of dissolved iron in the methanic zone (250
      350 cm). The higher copy numbers at these depths were also reflected by the
      relative sequence abundances of members of the candidate division JS1,
      methanogenic and Methanohalobium/ANME-3 related archaea. The distribution of
      these populations was strongly correlated to the profile of pore-water Fe(2+)
      while that of Desulfobacteraceae corresponded to the pore-water sulfate profile.
      Furthermore, specific JS1 populations also strongly co-varied with the
      distribution of Methanosaetaceae in the methanic zone. Our data suggest that the
      interplay among JS1 bacteria, methanogenic archaea and Methanohalobium/ANME-3
      related archaea may be important for iron reduction and methane cycling in deep
      methanic sediments of the Helgoland mud area and perhaps in other methane-rich
      depositional environments. 

PMID- 25983725
TI  - Estimating and mapping ecological processes influencing microbial community
      assembly.
AB  - Ecological community assembly is governed by a combination of (i) selection
      resulting from among-taxa differences in performance; (ii) dispersal resulting
      from organismal movement; and (iii) ecological drift resulting from stochastic
      changes in population sizes. The relative importance and nature of these
      processes can vary across environments. Selection can be homogeneous or variable,
      and while dispersal is a rate, we conceptualize extreme dispersal rates as two
      categories; dispersal limitation results from limited exchange of organisms among
      communities, and homogenizing dispersal results from high levels of organism
      exchange. To estimate the influence and spatial variation of each process we
      extend a recently developed statistical framework, use a simulation model to
      evaluate the accuracy of the extended framework, and use the framework to examine
      subsurface microbial communities over two geologic formations. For each
      subsurface community we estimate the degree to which it is influenced by
      homogeneous selection, variable selection, dispersal limitation, and homogenizing
      dispersal. Our analyses revealed that the relative influences of these ecological
      processes vary substantially across communities even within a geologic formation.
      We further identify environmental and spatial features associated with each
      ecological process, which allowed mapping of spatial variation in ecological
      process-influences. The resulting maps provide a new lens through which
      ecological systems can be understood; in the subsurface system investigated here
      they revealed that the influence of variable selection was associated with the
      rate at which redox conditions change with subsurface depth. 

PMID- 25983727
TI  - Molecular epidemiology and genetic diversity of Listeria monocytogenes isolates
      from a wide variety of ready-to-eat foods and their relationship to clinical
      strains from listeriosis outbreaks in Chile.
AB  - Listeria monocytogenes is a pathogen transmitted through food that can cause
      severe infections in high-risk groups such as pregnant women, elderly, young
      children and immunocompromised individuals. It is a ubiquitous bacterium that can
      survive in harsh conditions, such as dry environments, at low temperatures, in
      brine conditions and at low pH values. It also has the capacity to form biofilms,
      which makes it particularly successful even in colonizing surfaces within food
      processing plants. This study analyzed the presence of L. monocytogenes in ready
      to-eat food (RTE) such as sausage, cheese, fresh salads, and other types of raw
      food. 850 samples of refrigerated and packaged food collected in 2008 and 2009
      were analyzed. It was found that 25% of these samples were contaminated with L.
      monocytogenes strains. Serotyping and virulence genes detection by polymerase
      chain reaction (PCR) identified that strains belonging to serotype 4b, and
      containing one or more genes encoded by pathogenicity island (LIPI-1), were
      significantly associated with specific food types. Furthermore, using pulse field
      gel electrophoresis (PFGE), it was possible to associate isolates from cheese
      with strains from clinical cases of listeriosis outbreaks that occurred during
      the same time period within the same geographic regions. In addition, a strong
      correlation was observed between isolates from frozen seafood and from clinical
      strains obtained from sporadic cases of listeriosis. In agreement with reports
      described in other countries, our results shown that Chilean strains of L.
      monocytogenes from food products include the most virulent serotypes, encoding
      for the main virulence genes of the LIPI-1, and were clonally related to clinical
      isolates from sporadic cases and outbreaks of listeriosis. In conclusion, we show
      that Chilean isolates of L. monocytogenes from RTE and raw food products can
      cause disease in humans, representing a public health risk that justifies
      permanent surveillance. 

PMID- 25983726
TI  - Eukaryote-like Ser/Thr protein kinase PrkA modulates sporulation via regulating
      the transcriptional factor sigma(K) in Bacillus subtilis.
AB  - Protein kinase A (PrkA), also known as AMP-activated protein kinase, functions as
      a serine/threonine protein kinase (STPK), has been shown to be involved in a
      variety of important biologic processes, including pathogenesis of many important
      diseases in mammals. However, the biological functions of PrkA are less known in
      prokaryote cells. Here, we explored the function of PrkA as well as its
      underlying molecular mechanisms using the model bacterium Bacillus subtilis168.
      When PrkA is inhibited by 9-beta-D-arabinofuranosyladenine (ara-A) in the wild
      type strain or deleted in the DeltaprkA mutant strain, we observed sporulation
      defects in B. subtilis 168, suggesting that PrkA functions as a sporulation
      related protein. Transcriptional analysis using the lacZ reporter gene
      demonstrated that deletion of prkA significantly reduced the expression of the
      transcriptional factor sigma(K) and its downstream genes. Complementation of sigK
      gene in prkA knockout mutant partially rescued the phenotype of DeltaprkA,
      further supporting the hypothesis that the decreased sigma(K) expression should
      be one of the reasons for the sporulation defect resulting from prkA disruption.
      Finally, our data confirmed that Hpr (ScoC) negatively controlled the expression
      of transcriptional factor sigma(K), and thus PrkA accelerated sporulation and the
      expression of sigma(K) by suppression of Hpr (ScoC). Taken together, our study
      discovered a novel function of the eukaryotic-like STPK PrkA in spore development
      as well as its underlying molecular mechanism in B. subtilis. 

PMID- 25983728
TI  - Modulatory effects on dendritic cells by human herpesvirus 6.
AB  - Human herpesvirus 6A and 6B are beta-herpesviruses approaching 100%
      seroprevalance worldwide. These viruses are involved in several clinical
      syndromes and have important immunomodulatory effects. Dendritic cells (DC) are
      key players in innate and adaptive immunity. Accordingly, DC are implicated in
      the pathogenesis of many human diseases, including infections. In this review the
      effects of HHV-6 infection on DC will be discussed. 

PMID- 25983729
TI  - Editorial on plants as alternative hosts for human and animal pathogens.

PMID- 25983730
TI  - A novel assay for the detection of bioactive volatiles evaluated by screening of
      lichen-associated bacteria.
AB  - Volatile organic compounds (VOCs) produced by microorganisms are known both for
      their effect on pathogens and their role as mediators in various interactions and
      communications. Previous studies have demonstrated the importance of VOCs for
      ecosystem functioning as well as their biotechnological potential, but screening
      for bioactive volatiles remained difficult. We have developed an efficient
      testing assay that is based on two multi-well plates, separated by a sealing
      silicone membrane, two tightening clamps, and variable growth media, or
      indicators. The experiment design as presented here is a novel and robust
      technique to identify positive as well as negative VOC effects on the growth of a
      target organism and to test for specific substances e.g., hydrogen cyanide which
      can be detected with a suitable indicator. While the first pre-screening assay is
      primarily based on indicator color change and visible growth diameter reduction,
      we also introduce an advanced and quantitatively precise experiment design. This
      adaptation involves qPCR-based quantification of viable target cells after
      concluding the treatment with VOCs. Therefore, we chose preselected active
      isolates and compared the partial 16S rRNA gene copy number of headspace-exposed
      E. coli with non-treated controls. Separately obtained headspace SPME and GC/MS
      based profiles of selected bacterial isolates revealed the presence of specific
      and unique signatures which suggests divergent modes of action. The assay was
      evaluated by screening 100 isolates of lung lichen-associated bacteria.
      Approximately one quarter of the isolates showed VOC-based antibacterial and/or
      antifungal activity; mainly Pseudomonas and Stenotrophomonas species were
      identified as producers of bioactive volatiles. 

PMID- 25983733
TI  - Paralytic shellfish toxin content is related to genomic sxtA4 copy number in
      Alexandrium minutum strains.
AB  - Dinoflagellates are microscopic aquatic eukaryotes with huge genomes and an
      unusual cell regulation. For example, most genes are present in numerous copies
      and all copies seem to be obligatorily transcribed. The consequence of the gene
      copy number (CPN) for final protein synthesis is, however, not clear. One such
      gene is sxtA, the starting gene of paralytic shellfish toxin (PST) synthesis.
      PSTs are small neurotoxic compounds that can accumulate in the food chain and
      cause serious poisoning incidences when ingested. They are produced by
      dinoflagellates of the genera Alexandrium, Gymnodium, and Pyrodinium. Here we
      investigated if the genomic CPN of sxtA4 is related to PST content in Alexandrium
      minutum cells. SxtA4 is the 4th domain of the sxtA gene and its presence is
      essential for PST synthesis in dinoflagellates. We used PST and genome size
      measurements as well as quantitative PCR to analyze sxtA4 CPN and toxin content
      in 15 A. minutum strains. Our results show a strong positive correlation between
      the sxtA4 CPN and the total amount of PST produced in actively growing A. minutum
      cells. This correlation was independent of the toxin profile produced, as long as
      the strain contained the genomic domains sxtA1 and sxtA4. 

PMID- 25983731
TI  - Distinct summer and winter bacterial communities in the active layer of Svalbard
      permafrost revealed by DNA- and RNA-based analyses.
AB  - The active layer of soil overlaying permafrost in the Arctic is subjected to
      dramatic annual changes in temperature and soil chemistry, which likely affect
      bacterial activity and community structure. We studied seasonal variations in the
      bacterial community of active layer soil from Svalbard (78 degrees N) by co
      extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR
      amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were
      quantified and sequenced to test for the effect of low winter temperature and
      seasonal variation in concentration of easily degradable organic matter on the
      bacterial communities. The copy number of 16S rRNA genes and transcripts revealed
      no distinct seasonal changes indicating potential bacterial activity during
      winter despite soil temperatures well below -10 degrees C. Multivariate
      statistical analysis of the bacterial diversity data (DNA and cDNA libraries)
      revealed a season-based clustering of the samples, and, e.g., the relative
      abundance of potentially active Cyanobacteria peaked in June and
      Alphaproteobacteria increased over the summer and then declined from October to
      November. The structure of the bulk (DNA-based) community was significantly
      correlated with pH and dissolved organic carbon, while the potentially active
      (RNA-based) community structure was not significantly correlated with any of the
      measured soil parameters. A large fraction of the 16S rRNA transcripts was
      assigned to nitrogen-fixing bacteria (up to 24% in June) and phototrophic
      organisms (up to 48% in June) illustrating the potential importance of nitrogen
      fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic
      bacterial activity on the soil surface. 

PMID- 25983732
TI  - The Pho regulon: a huge regulatory network in bacteria.
AB  - One of the most important achievements of bacteria is its capability to adapt to
      the changing conditions of the environment. The competition for nutrients with
      other microorganisms, especially in the soil, where nutritional conditions are
      more variable, has led bacteria to evolve a plethora of mechanisms to rapidly
      fine-tune the requirements of the cell. One of the essential nutrients that are
      normally found in low concentrations in nature is inorganic phosphate (Pi).
      Bacteria, as well as other organisms, have developed several systems to cope for
      the scarcity of this nutrient. To date, the unique mechanism responding to Pi
      starvation known in detail is the Pho regulon, which is normally controlled by a
      two component system and constitutes one of the most sensible and efficient
      regulatory mechanisms in bacteria. Many new members of the Pho regulon have
      emerged in the last years in several bacteria; however, there are still many
      unknown questions regarding the activation and function of the whole system. This
      review describes the most important findings of the last three decades in
      relation to Pi regulation in bacteria, including: the PHO box, the Pi signaling
      pathway and the Pi starvation response. The role of the Pho regulon in
      nutritional regulation cross-talk, secondary metabolite production, and
      pathogenesis is discussed in detail. 

PMID- 25983734
TI  - The Hyaluronic Acid-HDAC3-miRNA Network in Allergic Inflammation.
AB  - We previously reported the anti-allergic effect of high molecular weight form of
      hyaluronic acid (HMW-HA). In doing so, HA targets CD44 and inhibits FcepsilonRI
      signaling and cross-talk between epidermal growth factor receptor (EGFR) and
      FcepsilonRI. We previously reported the role of histone deacetylases (HDACs) in
      allergic inflammation and allergic inflammation-promoted enhanced tumorigenic
      potential. We reported regulatory role of HA in the expression of HDAC3. In this
      review, we will discuss molecular mechanisms associated with anti-allergic effect
      of HA in relation with HDACs. The role of microRNAs (miRNAs) in allergic
      inflammation has been reported. We will also discuss the role of miRNAs in
      allergic inflammation in relation with HA-mediated anti-allergic effects. 

PMID- 25983735
TI  - Emerging knowledge of the organelle outer membranes - research snapshots and an
      updated list of the chloroplast outer envelope proteins.

PMID- 25983736
TI  - GM trees with increased resistance to herbivores: trait efficiency and their
      potential to promote tree growth.
AB  - Climate change, as well as a more intensive forestry, is expected to increase the
      risk of damage by pests and pathogens on trees, which can already be a severe
      problem in tree plantations. Recent development of biotechnology theoretically
      allows for resistance enhancement that could help reduce these risks but we still
      lack a comprehensive understanding of benefits and tradeoffs with pest resistant
      GM (genetically modified) trees. We synthesized the current knowledge on the
      effectiveness of GM forest trees with increased resistance to herbivores. There
      is ample evidence that induction of exogenous Bacillus thuringiensis genes reduce
      performance of target pests whereas upregulation of endogenous resistance traits
      e.g., phenolics, generates variable results. Our review identified very few
      studies estimating the realized benefits in tree growth of GM trees in the field.
      This is concerning as the realized benefit with insect resistant GM plants seems
      to be context-dependent and likely manifested only if herbivore pressure is
      sufficiently high. Future studies of secondary pest species and resistance
      evolution in pest to GM trees should be prioritized. But most importantly we need
      more long-term field tests to evaluate the benefits and risks with pest resistant
      GM trees. 

PMID- 25983738
TI  - Competition for nitrogen between Fagus sylvatica and Acer pseudoplatanus
      seedlings depends on soil nitrogen availability.
AB  - Competition for nitrogen (N), particularly in resource-limited habitats, might be
      avoided by different N acquisition strategies of plants. In our study, we
      investigated whether slow-growing European beech and fast-growing sycamore maple
      seedlings avoid competition for growth-limiting N by different N uptake patterns
      and the potential alteration by soil N availability in a microcosm experiment. We
      quantified growth and biomass indices, (15)N uptake capacity and N pools in the
      fine roots. Overall, growth indices, N acquisition and N pools in the fine roots
      were influenced by species-specific competition depending on soil N availability.
      With inter-specific competition, growth of sycamore maple reduced regardless of
      soil N supply, whereas beech only showed reduced growth when N was limited. Both
      species responded to inter-specific competition by alteration of N pools in the
      fine roots; however, sycamore maple showed a stronger response compared to beech
      for almost all N pools in roots, except for structural N at low soil N
      availability. Beech generally preferred organic N acquisition while sycamore
      maple took up more inorganic N. Furthermore, with inter-specific competition,
      beech had an enhanced organic N uptake capacity, while in sycamore maple
      inorganic N uptake capacity was impaired by the presence of beech. Although
      sycamore maple could tolerate the suboptimal conditions at the cost of reduced
      growth, our study indicates its reduced competitive ability for N compared to
      beech. 

PMID- 25983739
TI  - The bZIP transcription factor HY5 interacts with the promoter of the monoterpene
      synthase gene QH6 in modulating its rhythmic expression.
AB  - The Artemisia annua L. beta-pinene synthase QH6 was previously determined to be
      circadian-regulated at the transcriptional level, showing a rhythmic fluctuation
      of steady-state transcript abundances. Here we isolated both the genomic sequence
      and upstream promoter region of QH6. Different regulatory elements, such as G-box
      (TGACACGTGGCA, -421 bp from the translation initiation site) which might have
      effects on rhythmic gene expression, were found. Using the yeast one-hybrid and
      electrophoretic mobility shift assay (EMSA), we confirmed that the bZIP
      transcription factor HY5 binds to this motif of QH6. Studies with promoter
      truncations before and after this motif suggested that this G-box was important
      for the diurnal fluctuation of the transgenic beta-glucuronidase gene (GUS)
      transcript abundance in Arabidopsis thaliana. GUS gene driven by the promoter
      region immediately after G-box showed an arrhythmic expression in both light/dark
      (LD) and constant dark (DD) conditions, whereas the control with G-box retained
      its fluctuation in both LD and DD. We further transformed A. thaliana with the
      luciferase gene (LUC) driven by an 1400 bp fragment upstream QH6 with its G-box
      intact or mutated, respectively. The luciferase activity assay showed that a peak
      in the early morning disappeared in the mutant. Gene expression analysis also
      demonstrated that the rhythmic expression of LUC was abolished in the hy5-1
      mutant. 

PMID- 25983737
TI  - An auxin responsive CLE gene regulates shoot apical meristem development in
      Arabidopsis.
AB  - Plant hormone auxin regulates most, if not all aspects of plant growth and
      development, including lateral root formation, organ pattering, apical dominance,
      and tropisms. Peptide hormones are peptides with hormone activities. Some of the
      functions of peptide hormones in regulating plant growth and development are
      similar to that of auxin, however, the relationship between auxin and peptide
      hormones remains largely unknown. Here we report the identification of OsCLE48, a
      rice (Oryza sativa) CLE (CLAVATA3/ENDOSPERM SURROUNDING REGION) gene, as an auxin
      response gene, and the functional characterization of OsCLE48 in Arabidopsis and
      rice. OsCLE48 encodes a CLE peptide hormone that is similar to Arabidopsis CLEs.
      RT-PCR analysis showed that OsCLE48 was induced by exogenously application of IAA
      (indole-3-acetic acid), a naturally occurred auxin. Expression of integrated
      OsCLE48p:GUS reporter gene in transgenic Arabidopsis plants was also induced by
      exogenously IAA treatment. These results indicate that OsCLE48 is an auxin
      responsive gene. Histochemical staining showed that GUS activity was detected in
      all the tissue and organs of the OsCLE48p:GUS transgenic Arabidopsis plants.
      Expression of OsCLE48 under the control of the 35S promoter in Arabidopsis
      inhibited shoot apical meristem development. Expression of OsCLE48 under the
      control of the CLV3 native regulatory elements almost completely complemented
      clv3-2 mutant phenotypes, suggesting that OsCLE48 is functionally similar to
      CLV3. On the other hand, expression of OsCLE48 under the control of the 35S
      promoter in Arabidopsis has little, if any effects on root apical meristem
      development, and transgenic rice plants overexpressing OsCLE48 are
      morphologically indistinguishable from wild type plants, suggesting that the
      functions of some CLE peptides may not be fully conserved in Arabidopsis and
      rice. Taken together, our results showed that OsCLE48 is an auxin responsive
      peptide hormone gene, and it regulates shoot apical meristem development when
      expressed in Arabidopsis. 

PMID- 25983740
TI  - Retrieving nitrogen isotopic signatures from fresh leaf reflectance spectra:
      disentangling delta(15)N from biochemical and structural leaf properties.
AB  - Linking remote sensing methodology to stable isotope ecology provides a promising
      approach to study ecological processes from small to large spatial scales. Here,
      we show that delta(15)N can be detected in fresh leaf reflectance spectra of
      field samples along a spatial gradient of increasing nitrogen input from an N2
      fixing invasive species. However, in field data it is unclear whether delta(15)N
      directly influences leaf reflectance spectra or if the relationship is based on
      covariation between delta(15)N and foliar nitrogen content or other leaf
      properties. Using a (15)N-labeling approach, we experimentally varied delta(15)N
      independently of any other leaf properties in three plant species across
      different leaf developmental and physiological states. delta(15)N could
      successfully be modeled by means of partial least squares (PLSs) regressions,
      using leaf reflectance spectra as predictor variables. PLS models explained 53
      73% of the variation in delta(15)N within species. Several wavelength regions
      important for predicting delta(15)N were consistent across species and could
      furthermore be related to known absorption features of N-containing molecular
      bonds. By eliminating covariation with other leaf properties as an explanation
      for the relationship between reflectance and delta(15)N, our results demonstrate
      that (15)N itself has an inherent effect on leaf reflectance spectra. Thus, our
      study substantiates the use of spectroscopic measurements to retrieve isotopic
      signatures for ecological studies and encourages future development. Furthermore,
      our results highlight the great potential of optical measurements for up-scaling
      isotope ecology to larger spatial scales. 

PMID- 25983741
TI  - Farm animal genetic and genomic resources from an agroecological perspective.

PMID- 25983742
TI  - Living on the edge: timing of Rand Flora disjunctions congruent with ongoing
      aridification in Africa.
AB  - The Rand Flora is a well-known floristic pattern in which unrelated plant
      lineages show similar disjunct distributions in the continental margins of Africa
      and adjacent islands-Macaronesia-northwest Africa, Horn of Africa-Southern
      Arabia, Eastern Africa, and Southern Africa. These lineages are now separated by
      environmental barriers such as the arid regions of the Sahara and Kalahari
      Deserts or the tropical lowlands of Central Africa. Alternative explanations for
      the Rand Flora pattern range from vicariance and climate-driven extinction of a
      widespread pan-African flora to independent dispersal events and speciation in
      situ. To provide a temporal framework for this pattern, we used published data
      from nuclear and chloroplast DNA to estimate the age of disjunction of 17
      lineages that span 12 families and nine orders of angiosperms. We further used
      these estimates to infer diversification rates for Rand Flora disjunct clades in
      relation to their higher-level encompassing lineages. Our results indicate that
      most disjunctions fall within the Miocene and Pliocene periods, coinciding with
      the onset of a major aridification trend, still ongoing, in Africa. Age of
      disjunctions seemed to be related to the climatic affinities of each Rand Flora
      lineage, with sub-humid taxa dated earlier (e.g., Sideroxylon) and those with
      more xeric affinities (e.g., Campylanthus) diverging later. We did not find
      support for significant decreases in diversification rates in most groups, with
      the exception of older subtropical lineages (e.g., Sideroxylon, Hypericum, or
      Canarina), but some lineages (e.g., Cicer, Campylanthus) showed a long temporal
      gap between stem and crown ages, suggestive of extinction. In all, the Rand Flora
      pattern seems to fit the definition of biogeographic pseudocongruence, with the
      pattern arising at different times in response to the increasing aridity of the
      African continent, with interspersed periods of humidity allowing range
      expansions. 

PMID- 25983743
TI  - Telomere DNA recognition in Saccharomycotina yeast: potential lessons for the co
      evolution of ssDNA and dsDNA-binding proteins and their target sites.
AB  - In principle, alterations in the telomere repeat sequence would be expected to
      disrupt the protective nucleoprotein complexes that confer stability to
      chromosome ends, and hence relatively rare events in evolution. Indeed, numerous
      organisms in diverse phyla share a canonical 6 bp telomere repeat unit (5'-TTAGGG
      3'/5'-CCCTAA-3'), suggesting common descent from an ancestor that carries this
      particular repeat. All the more remarkable, then, are the extraordinarily
      divergent telomere sequences that populate the Saccharomycotina subphylum of
      budding yeast. These sequences are distinguished from the canonical telomere
      repeat in being long, occasionally degenerate, and frequently non-G/C-rich.
      Despite the divergent telomere repeat sequences, studies to date indicate that
      the same families of single-strand and double-strand telomere binding proteins
      (i.e., the Cdc13 and Rap1 families) are responsible for telomere protection in
      Saccharomycotina yeast. The recognition mechanisms of the protein family members
      therefore offer an informative paradigm for understanding the co-evolution of DNA
      binding proteins and the cognate target sequences. Existing data suggest three
      potential, inter-related solutions to the DNA recognition problem: (i)
      duplication of the recognition protein and functional modification; (ii)
      combinatorial recognition of target site; and (iii) flexibility of the
      recognition surfaces of the DNA-binding proteins to adopt alternative
      conformations. Evidence in support of these solutions and the relevance of these
      solutions to other DNA-protein regulatory systems are discussed. 

PMID- 25983745
TI  - Evaluating a pivot-based approach for bilingual lexicon extraction.
AB  - A pivot-based approach for bilingual lexicon extraction is based on the
      similarity of context vectors represented by words in a pivot language like
      English. In this paper, in order to show validity and usability of the pivot
      based approach, we evaluate the approach in company with two different methods
      for estimating context vectors: one estimates them from two parallel corpora
      based on word association between source words (resp., target words) and pivot
      words and the other estimates them from two parallel corpora based on word
      alignment tools for statistical machine translation. Empirical results on two
      language pairs (e.g., Korean-Spanish and Korean-French) have shown that the pivot
      based approach is very promising for resource-poor languages and this approach
      observes its validity and usability. Furthermore, for words with low frequency,
      our method is also well performed. 

PMID- 25983744
TI  - An ecosystem-scale perspective of the net land methanol flux: synthesis of
      micrometeorological flux measurements.
AB  - Methanol is the second most abundant volatile organic compound in the troposphere
      and plays a significant role in atmospheric chemistry. While there is consensus
      about the dominant role of living plants as the major source and the reaction
      with OH as the major sink of methanol, global methanol budgets diverge
      considerably in terms of source/sink estimates reflecting uncertainties in the
      approaches used to model, and the empirical data used to separately constrain
      these terms. Here we compiled micrometeorological methanol flux data from eight
      different study sites and reviewed the corresponding literature in order to
      provide a first cross-site synthesis of the terrestrial ecosystem-scale methanol
      exchange and present an independent data-driven view of the land-atmosphere
      methanol exchange. Our study shows that the controls of plant growth on the
      production, and thus the methanol emission magnitude, and stomatal conductance on
      the hourly methanol emission variability, established at the leaf level, hold
      across sites at the ecosystem-level. Unequivocal evidence for bi-directional
      methanol exchange at the ecosystem scale is presented. Deposition, which at some
      sites even exceeds methanol emissions, represents an emerging feature of
      ecosystem-scale measurements and is likely related to environmental factors
      favouring the formation of surface wetness. Methanol may adsorb to or dissolve in
      this surface water and eventually be chemically or biologically removed from it.
      Management activities in agriculture and forestry are shown to increase local
      methanol emission by orders of magnitude; they are however neglected at present
      in global budgets. While contemporary net land methanol budgets are overall
      consistent with the grand mean of the micrometeorological methanol flux
      measurements, we caution that the present approach of simulating methanol
      emission and deposition separately is prone to opposing systematic errors and
      does not allow taking full advantage of the rich information content of
      micrometeorological flux measurements.

PMID- 25983746
TI  - Hepatorenal syndrome: outcome of response to therapy and predictors of survival.
AB  - Aim. Treatment of hepatorenal syndrome (HRS) in patients with liver cirrhosis is
      still challenging and characterized by a very high mortality. This study aimed to
      delineate treatment patterns and clinical outcomes of patients with HRS
      intravenously treated with terlipressin. Methods. In this retrospective single
      center cohort study, 119 patients (median [IQR]; 56.50 [50.75-63.00] years of
      age) with HRS were included. All patients were treated with terlipressin and
      human albumin intravenously. Those with response to treatment (n = 65) were
      compared to the patient cohort without improvement (n = 54). Patient
      characteristics and clinical parameters (Child stage, ascites, hepatic
      encephalopathy, HRS type I/II, and initial MELD score) were retrieved. Univariate
      analysis of factors influencing the success of terlipressin therapy and Cox
      regression analysis of factors influencing survival was carried out. Results. One
      month survival was significantly longer in the group of responders (p = 0.048).
      Cox regression analysis identified age [Hazard ratio, 95% confidence interval
      (CI); 1.05, 1.01-1.09, resp.], alcohol abuse [HR 3.05, 95% CI 1.11-8.38],
      duration of treatment [HR 0.92, 95% CI 0.88-0.96], and MELD score [HR 1.08, 95%
      CI 1.02-1.14] to be independent predictors of survival. Conclusions. Survival of
      HRS patients after treatment depends on age, etiology of liver disease, and the
      duration of treatment. 

PMID- 25983747
TI  - Molecular mechanism of local drug delivery with Paclitaxel-eluting membranes in
      biliary and pancreatic cancer: new application for an old drug.
AB  - Implantation of self-expanding metal stents (SEMS) is palliation for patients
      suffering from inoperable malignant obstructions associated with biliary and
      pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed
      because SEMS are susceptible to occlusion by tumor in-growth. We reported
      recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an
      animal model. However, little is known about the molecular mechanisms by which
      paclitaxel-eluting stents attenuate tumor growth. We investigated the signal
      transduction pathways underlying the antiproliferative effects of a paclitaxel
      eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing
      nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted
      pancreatic/cholangiocarcinoma xenograft tumors by Western blot,
      immunoprecipitation, and immunofluorescence. The quantities of paclitaxel
      released into the tumor and plasma were determined by liquid chromatography
      tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the
      tumor inhibited angiogenesis, which involved suppression of mammalian target of
      rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and
      increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal
      interaction-related expression of proteins such as CD44, SPARC, matrix
      metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM
      inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by
      suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway. 

PMID- 25983748
TI  - TLR3 Plays Significant Roles against HBV-Associated HCC.
AB  - Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in
      immune signaling and plays a crucial role in survival by being able to recognize
      various viral components including double-stranded RNA (dsRNA). The role of TLR3
      in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not
      well understood. To investigate the ability of TLR3 in regulating HBV replication
      in HCC, 80 cases of human HCC were collected and their tissue microarray was
      made. In HCC cells, the expression and location of TLR3, hepatitis-associated
      virus, and interstitial immunoreactive cells were assayed with
      immunohistochemical staining. The apoptosis of tumor cells was also detected by
      TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial
      immunoreactive cells, and cells apoptosis in HCC were investigated. In addition,
      we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting
      HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively
      related to HBsAg infection and HCC with cirrhosis and promotes interstitial
      immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15
      cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results
      indicate that TLR3 signaling activity may be involved in immune responses against
      HBV in HCC. 

PMID- 25983749
TI  - KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative
      to Molecular Biology in Colorectal Cancer?
AB  - KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to
      undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody
      therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG
      island methylator phenotype and microsatellite instability. Currently, KRAS and
      BRAF evaluation is based on molecular biology techniques such as SNaPshot or
      Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin
      embedded (FFPE) samples, immunodetection would appear to be an attractive
      alternative for detecting mutations. Thus, our objective was to assess the
      validity of KRAS and BRAF immunodetection of mutations compared with the
      genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF
      genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody
      was tested on 33 FFPE colorectal tumor samples with known KRAS status.
      Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE
      tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor
      sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely,
      BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity
      (100%) in detecting V600E mutation. Although molecular biology remains the
      reference method for detecting KRAS mutation, immunohistochemistry could be an
      attractive method for detecting BRAF V600E mutation in colorectal cancer. 

PMID- 25983751
TI  - Inhibitory effect of endostar on specific angiogenesis induced by human
      hepatocellular carcinoma.
AB  - To investigate the effect of endostar on specific angiogenesis induced by human
      hepatocellular carcinoma, this research systematically elucidated the inhibitory
      effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We
      employed fluorescence quantitative Boyden chamber analysis, wound-healing assay,
      flow cytometry examination using a coculture system, quantitative analysis of
      tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media
      (HCM) and HepG2 compared with normal hepatocyte conditioned media (NCM) and L02.
      Then, we found that endostar as a tumor angiogenesis inhibitor could potently
      inhibit human umbilical vein endothelial cell (HUVEC) migration in response to
      HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the
      lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24
      hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar
      inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In
      vivo Matrigel plug formation was also significantly reduced by endostar in HepG2
      inducing system rather than in L02 inducing system. It could be concluded that,
      at cell level, endostar inhibited the angiogenesis-related biological behaviors
      of HUVEC in response to HCC, including migration, adhesion proliferation, and
      tube formation. At animal level, endostar inhibited the angiogenesis in response
      to HCC in Matrigel matrix. 

PMID- 25983750
TI  - Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR
      196a2 on Gastric Cancer Susceptibility.
AB  - Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs
      may play important role in the development of gastric cancer. It has been
      reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are
      associated with susceptibility to gastric cancer. The published results remain
      inconclusive or even controversial. A meta-analysis was conducted to
      quantitatively assess potential association between the two common SNPs and
      gastric cancer risk. Methods. A comprehensive literature search was performed in
      multiple internet-based electronic databases. Data from 12 eligible studies were
      extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95%
      CI). Results. C allele of rs2910164 is associated with reduced gastric cancer
      risk in heterozygote model and dominant model whereas rs11614913 indicates no
      significant association. Subgroup analysis demonstrates that C allele of
      rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric
      cancer in dominant model and recessive model, respectively, while rs11614913
      increased intestinal type gastric cancer in dominant model. Conclusion. SNPs
      rs2910164 and rs11614913 might have effect on gastric cancer risk in certain
      genetic models and specific types of cancer. Further well-designed studies should
      be considered to validate the potential effect. 

PMID- 25983753
TI  - High Doses of Caffeine during the Peripubertal Period in the Rat Impair the
      Growth and Function of the Testis.
AB  - Prenatal caffeine exposure adversely affects the development of the reproductive
      organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine
      exposure would also influence physiologic gonadal changes and function during
      this critical period for sexual maturation. This study investigated the impact of
      high doses of caffeine on the testes of prepubertal male rats. A total of 45
      immature male rats were divided randomly into three groups: a control group and 2
      groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4
      weeks. Caffeine caused a significant decrease in body weight gain, accompanied by
      proportional decreases in lean body mass and body fat. The caffeine-fed animals
      had smaller and lighter testes than those of the control that were accompanied by
      negative influences on the histologic parameters of the testes. In addition,
      stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved
      from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine
      consumption can interfere with the maturation and function of the testis,
      possibly by interrupting endogenous testosterone secretion and reducing the
      sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we
      confirmed that pubertal administration of caffeine reduced testis growth and
      altered testis histomorphology. 

PMID- 25983754
TI  - The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with
      Classic Type in the Patients with Coexisting Hashimoto's Thyroiditis.
AB  - Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare
      subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the
      salivary glands. Due to its rarity, the clinicopathologic and molecular features
      of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical
      treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and
      compared to 200 consecutive patients with classic PTC. BRAF mutation was tested
      with pyrosequencing. Results. There were no significant differences in age,
      predilection for women, multifocality, extrathyroidal extension, or lymph node
      metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly
      associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp.,
      P < 0.001) and showed significantly lower rate of BRAF mutation when compared to
      classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of
      BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis.
      When we compared WLPTC and classic PTC in the patients with coexisting
      Hashimoto's thyroiditis, there were no significant differences in
      clinicopathologic characteristics or the BRAF mutational rate between the two
      groups. Conclusions. Patients with WLPTC have similar demographic, clinical,
      pathologic, and molecular characteristics to those with classic PTC coexisting
      with Hashimoto's thyroiditis. 

PMID- 25983752
TI  - Zinc transporters and zinc signaling: new insights into their role in type 2
      diabetes.
AB  - Zinc is an essential trace element that plays a vital role in many biological
      processes including growth and development, immunity, and metabolism. Recent
      studies have highlighted zinc's dynamic role as a "cellular second messenger" in
      the control of insulin signaling and glucose homeostasis. Accordingly, mechanisms
      that contribute to dysfunctional zinc signaling are suggested to be associated
      with metabolic disease states including cancer, cardiovascular disease,
      Alzheimer's disease, and diabetes. The actions of the proteins that control the
      uptake, storage, and distribution of zinc, the zinc transporters, are under
      intense investigation due to their emerging role in type 2 diabetes. The
      synthesis, secretion, and action of insulin are dependent on zinc and the
      transporters that make this ion available to cellular processes. This suggests
      that zinc plays a previously unidentified role where changes in zinc status over
      time may affect insulin activity. This previously unexplored concept would raise
      a whole new area of research into the pathophysiology of insulin resistance and
      introduce a new class of drug target with utility for diabetes pharmacotherapy. 

PMID- 25983755
TI  - Mixed viral infections circulating in hospitalized patients with respiratory
      tract infections in kuwait.
AB  - The aim of this study was to determine the frequency of viral mixed detection in
      hospitalized patients with respiratory tract infections and to evaluate the
      correlation between viral mixed detection and clinical severity. Hospitalized
      patients with respiratory tract infections (RTI) were investigated for 15
      respiratory viruses by using sensitive molecular techniques. In total, 850
      hospitalized patients aged between 3 days and 80 years were screened from
      September 2010 to April 2014. Among the 351 (47.8%) patients diagnosed with viral
      infections, viral mixed detection was identified in 49 patients (14%), with human
      rhinovirus (HRV) being the most common virus associated with viral mixed
      detection (7.1%), followed by adenovirus (AdV) (4%) and human coronavirus-OC43
      (HCoV-OC43) (3.7%). The highest combination of viral mixed detection was
      identified with HRV and AdV (2%), followed by HRV and HCoV-OC43 (1.4%). Pneumonia
      and bronchiolitis were the most frequent reason for hospitalization with viral
      mixed detection (9.1%). There were statistical significance differences between
      mixed and single detection in patients diagnosed with bronchiolitis (P = 0.002)
      and pneumonia (P = 0.019). Our findings might indicate a significant association
      between respiratory virus mixed detection and the possibility of developing more
      severe LRTI such as bronchiolitis and pneumonia when compared with single
      detection. 

PMID- 25983757
TI  - Height augmentation in 11beta-hydroxylase deficiency congenital adrenal
      hyperplasia.
AB  - CONTEXT: 11beta-hydroxylase deficiency is the second most common form of
      congenital adrenal hyperplasia. Untreated, this enzyme deficiency leads to
      virilization, hypertension, and significant height impairment. PATIENT: We
      describe a patient from abroad who first presented to us at age 7 years for
      follow-up of ambiguous genitalia. He had been investigated and treated in
      Pakistan at 3-years-of-age following presentation for bilateral cryptorchidism.
      He was found to have 46, XX karyotype, elevated 17-OH progesterone and was
      diagnosed with congenital adrenal hyperplasia. In Pakistan, the patient had
      abdominal hysterectomy, bilateral salpingoophrectomy, and was started on
      corticosteroid replacement. At 7 years, shortly after immigrating to Canada,
      height was 138 cm and BMI 19.3 kg/m(2) (+2.9 SDS and +1.7 SDS, respectively, male
      growth chart) and blood pressure was greater than the 99th percentile for age and
      height. The patient had Prader stage III - IV genital anatomy. Bone age was
      significantly advanced, yielding a severely compromised predicted final adult
      height. Biochemical evaluation was consistent with 11beta-hydroxylase deficiency
      congenital adrenal hyperplasia. INTERVENTION AND OUTCOME: In an attempt to
      improve final height, in addition to glucocorticoid replacement, this patient was
      treated with recombinant growth hormone and a third generation aromatase
      inhibitor (Letrozole) with an improvement in final height attained as compared
      with predicted height. CONCLUSIONS: This case of a 46,XX patient raised as male
      with congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency
      highlights a number of unique and difficult treatment challenges; specifically,
      the role of new therapeutic options for optimization of growth in the context of
      prior suboptimal disease management.

PMID- 25983756
TI  - Midline cervical cleft: review of an uncommon entity.
AB  - Introduction. Midline cervical cleft is a rare congenital malformation which
      nonetheless has a classic presentation. This study presents one of the largest
      single series of new patients with MCC and provides an exhaustive review and
      catalogue of publications from the international literature. Materials and
      Methods. Retrospective chart review performed in two academic medical centers and
      literature review performed with primary verification of all quoted references.
      Results. Ten patients with MCC were identified (8 boys and 2 girls). All patients
      presented with the classic findings of this congenital anomaly, and the length of
      the skin defect correlated with an increase in the patient's age. Surgical
      excision was complete in all cases. Thorough international literature review
      yielded only 195 verifiable previously reported cases. Conclusions. This is one
      of the largest series of new patients with midline cervical cleft presented in
      the world literature. Although rare (with less than 200 cases published to date)
      this entity does have a reliable presentation that should lead to rapid and
      accurate diagnosis. Complete surgical excision at an early age is appropriate
      since the anomaly increases in length commensurate with the patient's age. 

PMID- 25983759
TI  - BC Medication Management Project: Perspectives of pharmacists, patients and
      physicians.
AB  - BACKGROUND: The BC Medication Management Project (BCMMP) was developed by the BC
      Ministry of Health and the BC Pharmacy Association. This pilot project ran from
      September 2010 to January 2012. Pharmacists reviewed patients' medication
      histories, discussed best use of medications, provided education and monitored
      for adverse effects, developed a plan to deal with medication issues and created
      a best possible medication history. METHODS: To evaluate the experience of
      participating in the BCMMP, challenges and strengths of the project and the
      alignment of these experiences with the overarching goals, focus groups and
      interviews were conducted with 6 stakeholder groups. Themes were compared within
      and across stakeholder type and descriptively analyzed. RESULTS: A total of 88
      people participated in the focus groups/interviews. Pharmacists stated that
      providing BCMMP services was professionally satisfying and concurred with
      patients that the service did benefit them. However, participating in the BCMMP
      was not seen as financially sustainable by pharmacy owners, and there were
      concerns about patient selection. Physicians expressed concerns about increased
      workload associated with the BCMMP, for which they were not compensated. The
      computer system and burden of documentation were identified as the greatest
      problems. CONCLUSIONS: The BCMMP pilot project was enthusiastically received by
      pharmacists and patients who felt that it benefited patients and moved the
      pharmacy profession in a positive direction. It was widely felt that the BCMMP
      could be successful and sustainable if the identified challenges are addressed.

PMID- 25983758
TI  - Primary ovarian insufficiency in adolescents: a case series.
AB  - BACKGROUND: Primary ovarian insufficiency (POI) is characterized by 4 to 6 months
      of amenorrhea and elevated serum FSH and LH in females less than 40 years.
      Ovarian insufficiency is uncommon in pediatrics and typically results from a
      chromosomal abnormality or treatment for malignancy. Idiopathic POI in which no
      apparent precipitant is identified is even rarer. After encountering three teens
      with idiopathic POI in recent months, we utilized an informatics-enabled search
      of the electronic medical records from our hospital to identify all cases of
      idiopathic POI presenting from 1998-2013. CASES PRESENTATION: 15 girls (ages 14.4
      to 17.9 years) met criteria for idiopathic POI. At diagnosis, breast development
      ranged from Tanner stage 1 to 5; 6 of 15 patients had secondary amenorrhea. All
      patients presented in the past 11 years and 13 of 15 in the past 5 years.
      CONCLUSIONS: In this first case series of POI from the United States, we observed
      a clustering at our institution in recent years. If an increased incidence of
      idiopathic POI is identified at other institutions, further investigation into
      potential environmental and genetic precipitants is warranted.

PMID- 25983760
TI  - Adherence to statin therapy in patients with type 2 diabetes: An important
      dilemma.
AB  - BACKGROUND: Despite the importance of patients' adherence to their drug
      treatments for achieving desired therapeutic goals and the proven role 3-hydroxy
      3-methylglutaryl coenzyme A inhibitors (statins) for the health status of
      patients with cardiovascular diseases, there is not enough information regarding
      diabetic patients' adherence to statin therapy in developing countries. In this
      clinical study we aimed to assess the adherence of diabetes type 2 patients to
      statin therapy in a research based community clinic in Iran. MATERIALS AND
      METHODS: In this prospective clinical study which was done at Isfahan
      Endocrinology and Metabolism Research Center, 204 diabetic type 2 patients under
      treatment with statin were interviewed twice and their demographic data (age,
      gender, body mass index, education), statin information (type, dose) and their
      serum lipid profile were recorded. Three months after the initial visits,
      patients were assessed using pill counting method and according to patients' self
      reporting and also assessed low-density lipoprotein (LDL) cholesterol goal
      attainment <100 mg/dl. RESULTS: Adherence rate was 79.7% and 69% according to
      pill counting and self-reporting among study population. Moreover, 68.4% of
      patients achieved their LDL cholesterol goal of <100 mg/dl and adherent patients
      reached therapeutic goal significantly more than those who were considered non
      adherence to statin therapy (P < 0.01). CONCLUSION: Adherence to statin therapy,
      as reflected by pill count method, is significantly related to LDL cholesterol
      goal achievement in patients with diabetes and dyslipidemia. Pill count method
      can be used to identify patients who are nonadherent to statin therapy and at
      high risk for failure to attain LDL cholesterol goals.

PMID- 25983761
TI  - Surveillance of acute respiratory infections among outpatients: A pilot study in
      Isfahan city.
AB  - BACKGROUND: Considering that there was not any regional survey in Isfahan, Iran
      regarding the epidemiology of acute respiratory tract infections (ARTI) in
      different age groups of general population, the aim of this study was to
      determine the epidemiologic feature of ARTIs in Isfahan using multiplex
      polymerase chain reaction (PCR) method. MATERIALS AND METHODS: In this cross
      sectional study, patients aged <80 years with symptoms of ARTI were studied,
      during 2009-2010 Nasopharyngeal and dry throat swab specimens were collected and
      pathogens of ARTI was determined using multiplex real-time PCR. RESULTS: In this
      study, 455 cases with ARTI were studied. Mean age of studied population was 29.9
      +/- 18.5 (range: 0.2-80). Symptoms such as sore throat (86.3%), coryza (68.0%)
      and dry cough (54.3%) were the most common symptoms in all studied groups,
      whereas fever was the most clinical presentation of younger patients (<15 years
      old) and headache and skeletal pain were the most common symptoms of older
      patients (>15 years old). Rhinovirus was the most common cause of ARTI in
      patients aged <5 years and those aged >50 years. Influenza virus B was the most
      common cause of ARTI in patients aged 5-50 years. CONCLUSION: Our study provides
      baseline information on the epidemiologic and clinical feature of outpatients
      with ARTIs in Isfahan city. Though our findings in this pilot study could be
      helpful in diagnosis, treatment, and prevention of ARTI, planning preventive
      interventional.

PMID- 25983762
TI  - Association of 25-hydroxy Vitamin D levels with indexes of general and abdominal
      obesity in Iranian adolescents: The CASPIAN-III study.
AB  - BACKGROUND: This study aimed to determine the association of serum 25-hydroxy
      Vitamin D (25(OH)D) levels with measures of general and abdominal obesity in
      Iranian adolescents. MATERIALS AND METHODS: This nationwide cross-sectional study
      was conducted among 1090 students, aged 10-18 years, living in 27 provinces in
      Iran. Serum concentration of 25(OH)D was analyzed quantitatively by direct
      competitive immunoassay chemiluminescence method. Body mass index (BMI) and waist
      to-height ratio (WHtR) were considered as measures of generalized and abdominal
      obesity, respectively. RESULTS: Study participants consisted of 1090 adolescents
      (51.9% boy and 67.1% urban residents) with mean age, BMI, and waist circumference
      of 14.7 (2.6) years, 19.3 (4.2) kg/m(2), and 67.82 (12.23) cm, respectively. The
      median serum 25(OH)D was 13.0 ng/mL (interquartile range: 20.6). Overall, 40% of
      participants were Vitamin D deficient, and 39% were Vitamin D insufficient. Serum
      25(OH)D level was not associated with BMI and WHtR. CONCLUSION: We did not
      document any significant association between serum 25(OH)D level and
      anthropometric measures in adolescents. This finding may be because of
      considerably high prevalence of hypovitaminosis D in the study population.

PMID- 25983763
TI  - The effect of highly active antiretroviral therapy on liver function in human
      immunodeficiency virus-infected pediatric patients with or without hepatitis
      virus co-infection.
AB  - BACKGROUND: Co-infection of hepatitis virus is common in human immunodeficiency
      virus (HIV) infected adults in China. But little is known about hepatitis virus
      co-infection in pediatric HIV-infected subjects. The study aimed to investigate
      the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection
      and highly active antiretroviral therapy (HAART) on liver function of pediatric
      HIV-infected subjects. MATERIALS AND METHODS: A cohort study including 101
      pediatric HIV-infected subjects with HBV/HCV co-infection and 44 pediatric
      comparators with HIV mono-infection was carried out in Henan Province of China
      from September 2011 to September 2012. All patients received HAART for 1-year.
      HBV and HCV infection was determined by antibody tests. HIV RNA load, CD4(+) T
      cell counts and liver function were determined before and after HAART. The
      Student's t-test or a one-way ANOVA was used for normally distributed values and
      A Mann-Whitney U-test was performed for values without normal distribution using
      SPSS statistical package 18.0 (SPSS Inc.). RESULTS: After HAART for 1-year, the
      median levels of viral load were decreased to lower limit of detection in 90.34%
      pediatric HIV-infected subjects with/without HBV/HCV co-infection (P < 0.001),
      and CD4(+) T-cell counts increased significantly (P < 0.001). Compared with the
      pre-HAART, mean level of alanine aminotransferase (ALT) in each group had a
      significant increase after HAART (P < 0.01). The mean levels of ALT and aspartate
      aminotransferase (AST) in nevirapine (NVP) based HAART group increased
      significantly after HAART (P < 0.01). Mean change values of ALT and AST were
      significantly higher in the NVP based regimen group than in the efavirenz (EFV)
      based regimen group (P < 0.01). For HIV/HBV/HCV co-infected patients, mean change
      values of ALT and AST in NVP-based HAART group was significantly higher than that
      in EFV-based HAART group (P < 0.01). CONCLUSION: Highly active antiretroviral
      therapy can damage liver function in pediatric HIV-infected subjects, especially
      in those with HBV/HCV co-infection. NVP was more harmful to liver function of
      pediatric HIV-infected subjects than EFV.

PMID- 25983764
TI  - Evaluation of different aspects of power Doppler sonography in differentiating
      and prognostication of breast masses.
AB  - BACKGROUND: We conducted our study on 1110 patients with breast masses in order
      to investigate different aspects of power Doppler sonography (PDS) for
      differentiating between benign and malignant breast lesions and their
      prognostication. MATERIALS AND METHODS: This study was conducted on the women who
      were referred to the sonography units of University Hospitals for breast
      sonography and had a BIRADS-3 mass or higher in gray scale sonography. Then, PDS
      was performed for all the patients. Vascularization, number of vessels,
      resistance index (RI), pulsatility index (PI), and vascularization patterns were
      evaluated for all the lesions. We compared our radiologic findings concerning
      different histopathologic and hormonal aspects of the lesions. RESULTS: The
      differences between mean vascular density in malignant lesions concerning size of
      the tumor, histological grade, stage, and hormone receptor status were
      statistically significant. Although, there was an overlap between benign and
      malignant values. A resistive index (RI) value higher than 0.83 as a sign for
      malignancy had sensitivity equal to 75% and specificity equal to 97% (P = 0.04
      and 0.03, respectively). A PI value higher than 1.6 has a sensitivity and
      specificity value of 70% and 98%, respectively, as a malignancy sign (P = 0.02
      and 0.04, respectively). CONCLUSION: It seems that while malignant tumors have
      significantly higher number of vessels in comparison to benign one, since the
      number of vessels overlap between benign and malignant tumors, this aspect has
      little clinical usefulness in distinguishing or prognostication of breast masses.
      In contrast RI, PI, and vascularization pattern have an ability to differentiate
      and predict the prognosis of breast lesions.

PMID- 25983765
TI  - A triple-blinded, randomized, placebo-controlled trial to examine the efficacy of
      buspirone added to typical antipsychotic drugs in patients with chronic
      schizophrenia.
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that the
      addition of buspirone, a partial agonist of 5HT1A receptor, to ongoing treatment
      with typical antipsychotics would improve the positive and negative symptoms in
      patients with chronic schizophrenia. MATERIALS AND METHODS: In this study, 50
      patients including 40 male and 10 female were recruited with chronic
      schizophrenia who were inpatients at psychiatric teaching hospital or asylums,
      aged between 18 and 65 years (mean age = 47 +/- 10.02). All patients were on the
      stable dose of typical antipsychotics for at least 1-month, and their acute
      symptoms were controlled. Patients were allocated in a random fashion: 25
      patients to buspirone at 30 mg/day plus typical antipsychotic and 25 patients to
      placebo plus typical antipsychotic. The positive and negative syndrome scale
      (PANSS), Simpson-Angus extrapyramidal rating scale (SAS) and mini mental state
      examination (MMSE), were administered at baseline, and 2, 4, and 6 weeks after
      the addition of buspirone. RESULTS: The 30 mg/day buspirone was well-tolerated,
      and no clinically important adverse effects were seen. There was no statistically
      significant difference between the two groups in MMSE and SAS scales. There was a
      significant reduction in subscales of negative, general, positive, and total of
      PANSS over the 6-week trial in buspirone group. There was a statistically
      significant difference between the two groups negative subscale (mean +/-
      standard deviation [SD] = 14.08 +/- 1.4 in buspirone group) P = 0.0219, general
      subscale (mean +/- SD = 27.42 +/- 2.1 in buspirone group) P = 0.0004, and total
      subscale (mean +/- SD = 55.63 +/- 3.9 in buspirone group) P = 0.0298, of PANSS in
      the 6-week of trial. CONCLUSION: The results suggest that adjunctive treatment
      with 5HT1A agonist such as buspirone may improve the negative symptoms of
      schizophrenia. Further studies are indicated to determine the efficacy of 5HT1A
      agonist treatment in chronic schizophrenia.

PMID- 25983766
TI  - Mid-term clinical outcome of radial shortening for kienbock disease.
AB  - BACKGROUND: To evaluate the intermediate-term outcomes of radius shortening as a
      treatment for Kienbock's disease. MATERIALS AND METHODS: In a historical cohort,
      16 skeletally mature patients (9 men and 7 women) with Kienbock disease, who were
      treated with radial shortening osteotomy between 2002 and 2012, were reviewed in
      our study. The mean age of our patients was 30 (range 18-43) years old. According
      to Litchman staging, there were 7 wrists at stage II and 9 wrists at stage III (6
      at stage IIIA and 3 at stage IIIB). The data of grip strength, pain (visual
      analog scale (VAS) score), wrist range of motion (ROM), ulnar variance (according
      to Palmer method), and the Lichtman stage were gathered before and after surgery.
      We evaluated overall wrist function using the Mayo Wrist score and disabilities
      of the arm shoulder and hand (DASH) score before surgery and at the last follow
      up. RESULTS: The average of follow-up was 7 years (range from 5 to 9 years).
      Preoperative ulnar variance was -1.3 mm (range from 2.5 to 1) preoperatively. The
      mean postoperative ulnar variance was 1 mm positive (range from 0.5 to 1.5). The
      VAS pain score, the mean arc of wrist flexion and extension, and grip strength
      improved significantly preoperatively compared to after recovery from surgery.
      The Lichtman stage was unchanged in nine patients, one grade worse in six
      patients, and one grade better in one patient. The mean DASH and Mayo scores
      improved significantly postoperatively compare with preoperation. Comparing
      preoperative positive, neuter, and negative ulnar variance, there was no
      significant difference in terms of VAS, DASH, and Mayo scores as well as ROM and
      grip strength. CONCLUSION: Our study shows that radius shortening surgery
      improves pain and disability regardless of ulnar variance.

PMID- 25983767
TI  - The effect of age on result of straight leg raising test in patients suffering
      lumbar disc herniation and sciatica.
AB  - BACKGROUND: Ninety percent of all people sometimes during their lives experience
      low back pain, and 30-40% develops radicular leg pain with the sciatica
      characteristics. Although for clinical diagnosis of lumbar disc herniation (LDH)
      straight leg raising (SLR) test in 85-90% of cases indicates LDH, but in our
      practice with LDH patients this test is frequently negative despite radicular leg
      pain due to LDH. Hence, we decided to evaluate this test in LDH in different age
      groups. MATERIALS AND METHODS: All patients with leg pain referring to
      neurosurgery clinic were enrolled. Those with a history of pain other than
      sciatica excluded and SLR test and magnetic resonance imaging (MRI) of the
      lumbosacral spine performed. The patients with negative MRI findings excluded and
      finally 269 patients with true sciatica and positive MRI were included. SLR tests
      were performed for different age groups. RESULTS: Of 269 patients, 167 were male.
      The age range was 16-80 years. The most involved levels were L5-S1 (47%) and L4
      L5 (42%), respectively. The rate of positive SLR result, which was 100%, 87% and
      82% for 10-19, 20-29 and 30-39 years age group respectively. With an increment of
      age, the rate of positive test regularly declined. The chance of positive SLR in
      men is 1.3 times the women (odds ratio [OR] 2.4; 95% confidence interval [CI] =
      1.265-4.557; P = 0.007). Increasing the age has suppression effect in positivity
      of SLR so that for each 1-year the chance of SLR become 0.27 times less to become
      positive and this is also statically meaningful (OR = 0.271;95% CI = 0.188-0.391;
      P,0.001). The chance of positive SLR for patients under 60 is 5.4 folds more than
      patients above 60 years old (OR = 5.4; 95% CI = 4-8.3; P, 0.001). CONCLUSION:
      Age, sex (male), and disk level had statistically the effect on SLR positive
      test.

PMID- 25983636
TI  - A measurement of the ratio of the production cross sections for [Formula: see
      text] and [Formula: see text] bosons in association with jets with the ATLAS
      detector.
AB  - The ratio of the production cross sections for [Formula: see text] and [Formula:
      see text] bosons in association with jets has been measured in proton-proton
      collisions at [Formula: see text] with the ATLAS experiment at the Large Hadron
      Collider. The measurement is based on the entire 2011 dataset, corresponding to
      an integrated luminosity of [Formula: see text]. Inclusive and differential cross
      section ratios for massive vector bosons decaying to electrons and muons are
      measured in association with jets with transverse momentum [Formula: see text]
      and jet rapidity [Formula: see text]. The measurements are compared to next-to
      leading-order perturbative QCD calculations and to predictions from different
      Monte Carlo generators implementing leading-order matrix elements supplemented by
      parton showers.

PMID- 25983769
TI  - Pancreatic anastomosis leakage management following pancreaticoduodenectomy how
      could be manage the anastomosis leakage after pancreaticoduodenectomy?
AB  - BACKGROUND: Pancreatic anastomosis leakage and fistula formation following
      pancreaticoduodenectomy (Whipple's procedure) is a common complication. Delay in
      timely diagnosis and proper management is associated with high morbidity and
      mortality. To report our experience with management of pancreatic fistula
      following Whipple's procedure. MATERIALS AND METHODS: In this retrospective
      study, medical records of 90 patients who underwent Whipple's procedure from 2009
      to 2013 at our medical center were reviewed for documents about pancreatic
      anastomosis leakage and fistula formation. RESULTS: There were 15 patients who
      developed pancreatico-jejunal anastomosis leakage. In 6 patients (3 males and 3
      females) the leakage was mild (conservative therapy was administered), but in 9
      patients (6 males and 3 females), there was severe leakage. For the latter group,
      surgical intervention was done (2 cases underwent re-anastomosis and for 7 cases
      pancreatico-jejunal stump ligation was done along with drainage of the location).
      CONCLUSION: In severe pancreatic anastomotic leakage, it is better to intervene
      surgically as soon as possible by debridement of the distal part of the pancreas
      and ligation of the stump with nonabsorbable suture. Furthermore, debridement of
      the jejunum should be done, and the stump should be ligated thoroughly along with
      drainage.

PMID- 25983768
TI  - Tumor microsatellite instability and clinicopathologic features in Iranian
      colorectal cancer patients at risk for Lynch syndrome.
AB  - BACKGROUND: Microsatellite instability (MSI) is a mutational signature that is
      the hallmark of Lynch syndrome, and MSI testing is a cost-effective method to
      screen the disease. Since there is no enough data about MSI status and associated
      clinicopathologic features of hereditary nonpolyposis colorectal cancer (HNPCC)
      in Iran, our study is a new trial to describe them in center of Iran (Isfahan).
      MATERIALS AND METHODS: It is a descriptive retrospective study to screen HNPCC
      families using Amsterdam II criteria in Central Iran within 2000-2013. For MSI
      testing, we used a commercially available kit evaluating mononucleotide markers
      (BAT-25, BAT-26, MON0-27, NR-21 and NR-24). After a fluorescent multiplex
      polymerase chain reaction amplification of the markers, samples were sequenced to
      fragment analysis. Data analysis was performed using SPSS 16 software (SPSS Inc.,
      Chicago, IL, USA). RESULTS: Overall, 31 of 45 screened HNPCC families were
      eventually included to MSI testing. Totally, 9/31 patients (29.0%) showed MSI in
      their tumor tissues. BAT-26 was the most instable marker with instability in 7/24
      MSI tumors (29.2%). The mean age at diagnosis in microsatellite stable (MSS), MSI
      Low (MSI-L), and MSI-High (MSI-H) probands was respectively 44.7 (standard
      deviation [SD] = 11.83), 51.7 (SD = 16.17), and 36.0 (SD = 3.41) years. The most
      common tumor sites in MSS, MSI-L, and MSI-H probands were rectosigmoid (~72.8%),
      rectum (66.7%) and right colon (50.0%), respectively. Of 186 cancer patients
      among 31 HNPCC families, 86 patients (46.2%) had colorectal cancer (CRC) and 100
      patients (53.8%) had extracolonic cancers. The average of CRC affected members
      among MSS, MSI-L, and MSI-H groups of our HNPCC families was 2.2 (SD = 1.30), 3.3
      (SD = 3.21), and 4.7 (SD = 2.42) patients per family, respectively. Stomach with
      18.3% and 26.7% of all extracolonic cancers were most common involved organ in
      MSS and MSI-H families, respectively. CONCLUSION: Our different molecular results
      could be suggested to describe HNPCC families based on some new molecular
      mechanisms leading to MSS HNPCC phenotypes. Meanwhile, more evaluations within
      our population are recommended.

PMID- 25983770
TI  - Cardiovascular manifestations of anabolic steroids in association with
      demographic variables in body building athletes.
AB  - BACKGROUND: The most common drug abuse among athletes is anabolic steroids which
      lead to the development of cardiovascular diseases and sudden death. Thus, the
      aim of this study was to evaluate cardiovascular outcomes of anabolic consumption
      in body building athletes. MATERIALS AND METHODS: Totally, 267 male athletes at
      the range of 20-45 years old with the regular consumption of anabolic steroids
      for >2 months with at least once weekly. High-density lipoprotein (HDL), low
      density lipoprotein (LDL), triglyceride (TG), and hematocrit (Hct) levels were
      measured after 10 h of fasting. Data analysis was performed using K2, t-test,
      ANOVA and correlation coefficient through SPSS 17. RESULTS: There was a
      nonsignificant difference between groups regarding HDL, TG, and total
      cholesterol. There was a significant decrease in the total and categorized LDL
      and Hct levels in consumers of anabolic steroid versus nonusers (P = 0.01 and P =
      0.041, respectively). Results showed a significant increase in systolic and
      diastolic blood pressure (SBP and DBP) in anabolic steroid users which associates
      with duration of abuse (P = 0.02 and P = 0.03, respectively). No significant
      electrocardiography changes were found within the follow-up period. CONCLUSION:
      Increase in SBP or DBP is a common complication of these drugs which can lead
      serious vascular disorders. The lower LDL cholesterol level might be due to the
      higher amounts of lipid consumption in these athletes.

PMID- 25983654
TI  - Measurement of the inclusive 3-jet production differential cross section in
      proton-proton collisions at 7 TeV and determination of the strong coupling
      constant in the TeV range.
AB  - This paper presents a measurement of the inclusive 3-jet production differential
      cross section at a proton-proton centre-of-mass energy of 7 TeV using data
      corresponding to an integrated luminosity of 5[Formula: see text]collected with
      the CMS detector. The analysis is based on the three jets with the highest
      transverse momenta. The cross section is measured as a function of the invariant
      mass of the three jets in a range of 445-3270 GeV and in two bins of the maximum
      rapidity of the jets up to a value of 2. A comparison between the measurement and
      the prediction from perturbative QCD at next-to-leading order is performed.
      Within uncertainties, data and theory are in agreement. The sensitivity of the
      observable to the strong coupling constant [Formula: see text] is studied. A fit
      to all data points with 3-jet masses larger than 664 GeV gives a value of the
      strong coupling constant of [Formula: see text].

PMID- 25983771
TI  - Sentinel lymph node mapping in early stage of endometrial and cervical cancers.
AB  - BACKGROUND: The sentinel lymph node (SLN) is defined as the first chain node in
      the lymphatic basin that receives primary lymphatic flow. If the SLN is negative
      for metastatic disease, then other nodes are expected to be disease-free. SLN
      techniques have been extensively applied in the staging and treatment of many
      tumors, including melanoma, breast and vulvar cancers. This study aims to
      evaluate our technique in SLN mapping in early stage endometrial and cervical
      cancers. MATERIALS AND METHODS: We scheduled a cross-sectional pilot study for
      patients undergoing staging surgery for endometrial and cervical cancer from
      November 2012 to February 2014 in Beheshti and Sadoughi Hospitals. Our SLN
      mapping technique included 1 h preoperative or intraoperative injection of 4 ml
      of 1% methylene blue dye in the tumor site. At the time of surgery, blue lymph
      nodes were removed and labeled as SLNs. Then systematic lymph node dissection was
      completed, and all of the nodes were sent for pathologic examination concerning
      metastatic involvement. All of the sentinel nodes were first stained with
      hematoxylin and eosin and examined. Those negative in this study were then
      stained with immunohistochemistry using anti-keratin antibody. Descriptive
      statistics, sensitivity, negative predictive values (NPV), false negative (FN)
      and detection rates were calculated. RESULTS: Twenty-three patients including 62%
      endometrial and 38% cervical cancers enrolled in the study. Median of SLN count
      in the endometrial and cervical cancers was 3 and 2, respectively. Among
      endometrial and cervical cancers, detection rate of metastatic disease was 80%
      and 87.5%, respectively. The FN rate for this technique was 0 and the sensitivity
      and NPV are 100% for both endometrial and cervical cancers. CONCLUSION:
      Considering the lower risk of metastases in early stage of both endometrial and
      cervical cancers, SLN technique allows for confident and accurate staging of
      cancer.

PMID- 25983772
TI  - Serum levels of glucagon-like peptide (GLP)-1 and GLP-2 in patients with
      Hashimoto's thyroiditis.
AB  - BACKGROUND: The influence of Hashimoto's thyroiditis (HT) with subclinical
      hypothyroidism or euthyroid status on the alteration of glucagon-like peptide
      (GLP)-1 and GLP-2 levels remains uncertain. MATERIALS AND METHODS: Twenty-four
      untreated HT patients with subclinical hypothyroidism, 24 euthyroid HT patients,
      and 24 age- and gender-matched controls were enrolled in the study. The levels of
      GLP-1, GLP-2, glucose, glycated albumin, insulin, thyroid hormone, and thyroid
      autoantibodies were measured and evaluated. RESULTS: The levels of GLP-1, blood
      glucose, and triglyceride were higher in HT patients with subclinical
      hypothyroidism than in controls (all P < 0.05, respectively). However, the above
      variables, including GLP-2, were similar in euthyroid patients and controls.
      Neither GLP-1 nor GLP-2 was correlated with thyroid hormone, thyroid
      autoantibodies or metabolic parameters. CONCLUSION: The serum levels of GLP-1,
      not GLP-2, were increased in patients with subclinical hypothyroidism. Our data
      suggest that subclinical hypothyroidism affects circulating GLP-1 levels.

PMID- 25983778
TI  - Comment on: Seroprevalence of hepatitis B virus and human immunodeficiency virus
      among young prisoners.

PMID- 25983773
TI  - Specific dietary patterns and concentrations of adiponectin.
AB  - BACKGROUND: One of the adipokines mostly secreted from adipose tissue is
      adiponectin. Adiponectin is well known as the anti-diabetic, anti-obesity and
      cardio-protective factor. Present study focused on the review the previous
      studies about relationship between adherence to healthy dietary pattern,
      independent of one or two special dietary components, and concentration of
      adiponectin. MATERIALS AND METHODS: We searched in PubMed search engine from 2003
      to July 2014 using the following key words: Healthy dietary pattern,
      mediterranean dietary pattern, dietary pattern, diet intervention and adiponectin
      and adipokines. Then, we recruited 10 articles to review in the present study.
      RESULTS: Cohort studies that are examined this relationship among women showed
      the strong positive association in this regard. According to cross-sectional
      studies adherence to healthy dietary pattern like Mediterranian intervention with
      moderate weight loss had a positive association with concentration of
      adiponectin. CONCLUSION: It seems that adherents to the healthy dietary patterns
      have great levels of circulating adiponectin. However, it is not clear that
      whether the separate components of healthy dietary patterns like good sources of
      fats or protein or fibers mostly have important roles in these beneficial effects
      of such dietary patterns or not.

PMID- 25983777
TI  - Hydatid cyst with intracavitary fungal ball: Does it require lung resection?

PMID- 25983779
TI  - Bullous dermatosis of childhood induced by gemfibrozil.

PMID- 25983775
TI  - Unilateral twin tubal ectopic pregnancy in a patient following tubal surgery.
AB  - We report a spontaneous unilateral live tubal twin pregnancy in a patient with a
      history of previous ectopic pregnancy (EP) and tubal surgery. Transvaginal
      ultrasound showed one pregnancy sac containing two fetal poles with cardiac
      activity, which appeared to be sited within the right adnexum. The right tubal EP
      was removed by salpingectomy. Ultrasound findings of suspected adnexal mass and
      free liquid in the Douglas pouch along with an increased a beta-human chorionic
      gonadotrophin levels, especially in association of risk factors, can help the
      early diagnosis of EP and reduce the related mortality and morbidity. 

PMID- 25983780
TI  - Clinical outcome and influencing factor for repeat lumbar discectomy for
      ipsilateral recurrent lumbar disc herniation.
AB  - OBJECTIVE: Recurrent herniation following disc excision has been reported in 5
      15% of patients. There have been numerous studies of recurrent disc herniation,
      but these have analyzed mixed patient populations. We designed this study to
      analyze the factors that influencing the clinical results, and efficiency of
      repeat discectomy for recurrent lumbar disc herniation occurring at the same
      level and on the same side after primary discectomy. METHODS: Between 1990 and
      2011, a total of 52 patients who underwent repeat discectomy for recurrent lumbar
      disc herniation were retrospectively analyzed. Clinical outcomes were measured
      with Macnab criteria and visual analog scale (VAS score). Clinical parameters
      were also analyzed for influencing factors for outcome. RESULTS: Based on Macnab
      criteria, an excellent surgical outcome was achieved in 28 cases (54%), a good
      outcome in 22 cases (42%), a fair outcome in 1 case (2%), and a poor outcome in 1
      case (2%). Based on VAS score, 47 of 52 patients (90%) showed more than 4 score
      improvement. Age, sex, diabetes mellitus, smoking, time interval between repeat
      and primary discectomy, duration of recurrent symptoms, and extent of disc
      herniation did not significantly affect Macnab criteria and VAS score. However, a
      traumatic event showed less VAS score improvement whereas not affecting on Macnab
      criteria. CONCLUSION: Conventional open lumbar discectomy performed as repeat
      surgery for recurrent herniation showed satisfactory results. Based on the
      results of this study, repeat discectomy can be recommended for the management of
      recurrent lumbar disc herniation. Further study is needed to evaluate factors
      related to the outcomes of repeat discectomy.

PMID- 25983784
TI  - Ossified Ligamentum Flavum causing Cervical Myelopathy.
AB  - Ossification of the ligamentum flavum (OLF) causing compressive cervical
      myelopathy or radiculopathy is rare. A 50-year-old male was admitted for
      progressive hypesthesia and paresthesia of both hands and a gradually worsening
      gait. MRI and CT scans demonstrated ossification of the left ligamentum flavum
      with dural sac and cord compression at the C5-6 level. The ossified ligamentum
      flavum was removed through a subtotal laminectomy and left side foraminotomy of
      the C5-6. Postoperatively, his gait improved remarkably and the sensory symptoms
      gradually resolved. 

PMID- 25983782
TI  - Comparison of Operating Time between Stand-alone Cage and a Standard Method for a
      Single Level Cervical Disc Disease.
AB  - OBJECTIVE: Autologous bone graft with anterior plating had been a standard method
      for anterior cervical discectomy and fusion (ACDF). Drawbacks of a standard
      method were donor site problem and problem associated with anterior plate. The
      stand-alone cage was introduced to reduce such problems. However, problems
      associated with subsidence and local kyphosis at the index level (segmental
      kyphosis) still persist with stand-alone cage and a standard method would be
      required in some cases. It seems that harvest of autologous bone and anterior
      plating procedure is time consuming, but this has not been verified. The aim of
      this study was to compare the operating time between patients operated on with
      stand-alone cage versus a standard method for single-level cervical disc disease.
      METHODS: Consecutive 29 patients (M:F=18:11; mean age, 58.4+/-12.4 years), who
      had undergone ACDF for single-level disc disease by a single surgeon from
      incision to closure during 2009-2011, were selected for this retrospective study.
      Seventeen patients were operated with stand-alone cage (Group I), and twelve
      patients were with a standard method (Group II). Operating time (from incision to
      closure), estimated blood loss, clinical and radiological outcomes were compared.
      Follow-up period was 11.4+/-6.3 months. RESULTS: Operating time was not different
      between groups longer; Group I (96.1+/-28.7 minutes) and Group II (112.4+/-31.7
      minutes) (p=0.13). There was no surgery related complication. Excellent or good
      outcome was achieved in 11 and 10 patients of group I and II, respectively. Bony
      fusion was achieved in 15 and 10 patients of group I and II respectively, while
      one subsidence occurred in each group. Postoperative segmental angle at the index
      level and cervical curvature was not different between groups. No patient
      complained donor site pain at the last follow-up. CONCLUSIONS: ACDF with a
      standard method for single-level cervical disc disease was not a time-consuming
      procedure comparing stand-alone cage.

PMID- 25983776
TI  - Co-infection of invasive pulmonary aspergillosis and cutaneous Fusarium infection
      in a patient with pyoderma gangrenosum.
AB  - We report an unusual case of co-infection of invasive pulmonary aspergillosis
      (IPA) and fusarial skin infection in a patient with classic pyoderma gangrenosum
      with unknown causes, which were previously controlled with oral prednisolone,
      cyclosporine. The diagnosis was made on direct microscopy and culture of
      endobronchial washing, bronchoalveolar lavage and skin lesion biopsy. The
      treatment failed, and the patient expired 12 days following hospitalization. This
      report highlights the rarity of coexistence of IPA and a chronic fusarial skin
      infection and thereby reinforcing the physician's attention toward the
      possibility of invasive fungal infection in the immunosuppressed patients. 

PMID- 25983781
TI  - Clinical outcomes of spinal epidural abscess.
AB  - OBJECTIVE: The aim of this study is to elucidate the clinical characteristics of
      patients with spinal epidural abscess (SEA) and demonstrate the risk factors,
      treatments and neurologic outcomes. METHODS: We retrospectively reviewed the
      medical records and radiologic images of 35 patients admitted to our department
      with SEA between March 1987 and April 2011. While we performed decompressive
      laminectomy and abscess drainage on 19 patients (54.3%), and 16 patients (45.7%)
      initially received conservative therapy with antibiotics alone. Medical Research
      Council (MRC) scale was applied to estimate results objectively. RESULTS: The
      neurological outcome data showed improved MRC scale from 14 (40%) patients. 13
      (37.1%) patients showed unchanged MRC scale and 8 (22.9%) patients revealed
      worsened MRC scale at the time of discharge. The patients with surgical treatment
      showed more improved MRC scale than the patients with conservative treatment and
      this was statistically significant (p=0.001) on univariate analysis. Initially,
      patients with decreased MRC scale and rapidly progressing neurological deficit
      underwent emergency surgery within 24 hours. Patients with intact MRC scale and
      minor neurological deficit received delayed surgery or conservative management
      with antibiotics. Among 19 patients those who experienced emergent operations
      within 24 hours showed better prognosis than those who underwent delayed
      operations after 24 hours. CONCLUSION: Surgical treatment is the modality of
      choice in patients with SEA and urgent surgery especially is indicated in
      patients with neurological deficits. And early surgery is more effective in
      neurological improvements than delayed surgery and conservative management.

PMID- 25983788
TI  - Idiopathic lumbosacral spinal chronic subdural hematoma.
AB  - Reports of spontaneous spinal chronic subdural hematoma (SDH) are extremely rare.
      In the limited cases reported, the origin, symptoms and treatments are diversely
      revealed. Therefore accurate diagnoses and proper treatments are difficult to
      determine. We report a 74-year-old male presented with severe low back pain and
      both buttocks pain. Magnetic resonance imaging showed a diffuse subdural
      infiltrating mass compress nerve roots at the level of L2-S2. Emergency operation
      for decompression and excision of mass revealed spinal chronic SDH. His pain was
      subsided after the operation. We report a rare case of idiopathic lumbosacral
      spinal chronic SDH and discuss various causes and treatments. 

PMID- 25983783
TI  - Radiological analysis of symptomatic complications after bilateral laminotomy for
      lumbar spinal stenosis.
AB  - OBJECTIVE: The purpose of this study was to describe the various symptomatic
      complications following decompressive bilateral laminotomy for treating lumbar
      spinal stenosis. METHODS: Out of 878 patients who underwent decompressive
      laminotomy from 2006 through 2008, 178 patients who were able to be followed for
      a minimum of 24 months were included in this study. The mean age at the time of
      surgery was 64.4 years (range, 38-79), and the average follow-up period was 32.7
      months. The development of symptomatic complications was observed using simple
      radiographs and MR imaging during the follow-up period. Imaging and clinical
      complications were focused on postoperative spondylolisthesis, disc herniation,
      and facet cysts, and were analyzed according to developmenttime, the degree of
      symptom, and their course. RESULTS: Postoperative simple radiographs revealed
      that eight out of 178 patients (4.4%) had developed symptomatic spondylolisthesis
      and six required an interbody fusion procedure. Five patients with disc
      herniation (2.8%) at the level of the decompressive bilateral laminotomy site
      underwent another operation within 24 months after the first surgery. In two
      patients, disc herniations developed within 1 month after surgery. Three (1.7%)
      out of 178 patients showed facet cysts but all symptoms were relieved by
      conservative treatment. Spontaneous regression of the cysts was observed during
      the follow-up period. CONCLUSIONS: Although decompressive bilateral laminotomy
      for spinal stenosis is believed to effective and reduces the need for fusion,
      various symptomatic complications were observed after this procedure. It is
      important to be aware of the possibility for these various complications to
      improve the surgical outcome.

PMID- 25983786
TI  - Lymphomatoid granulomatosis with spinal involvement after childhood acute
      lymphoblastic leukemia.
AB  - Lymphomatoid granulomatosis (LYG) is a lymphoproliferative disease involving the
      lungs most frequently; however, it may also involve the kidneys, skin and
      especially the central nervous system. Unique initial presentation of spinal
      involvement is extremely rare and epidural lesion of thoracic spine has not been
      reported. The prognosis for LYG has been reported to be poor, and there currently
      exists no satisfactory established treatment protocol. The purpose of this study
      is to report a case of successful treatment with surgery and rituximab
      combination therapy in thoracic spinal LYG. 

PMID- 25983785
TI  - Late onset tuberculous spondylitis following kyphoplasty: a case report and
      review of the literature.
AB  - A 76-year-old woman with compression fracture of L1 underwent percutaneous
      balloon kyphoplasty using polymethyl methacrylate. Three years after kyphoplasty
      of L1, the patient was readmitted with severe low back pain. Magnetic resonance
      imaging revealed progressive collapse of L1 vertebra and new compression fracture
      at T12. There were no signs of infection. As conservative treatment failed,
      combined surgery consisting of anterior corpectomy of T12 and L1, interposition
      of a titanium mesh cage filled with autologous rib graft, and anterior
      instrumentation of T11-L2 was performed. Histologic examination showed
      granulomatous inflammation surrounding the cement. Polymerase chain reaction and
      culture of the specimen confirmed the diagnosis of tuberculosis. The anti
      tuberculous medications were administered for 10 months, and the patient
      recovered without any sequelae. Tuberculous spondylitis should be included in the
      differential diagnosis of spondylitis after cement augmentation. If conservative
      antibiotic therapy fails, resection of the infected bone-cement complex is
      indicated. 

PMID- 25983774
TI  - Experimental treatments for mitochondrial dysfunction in sepsis: A narrative
      review.
AB  - Sepsis is a systemic inflammatory response to infection. Sepsis, which can lead
      to severe sepsis, septic shock, and multiple organ dysfunction syndrome, is an
      important cause of mortality. Pathogenesis is extremely complex. In recent years,
      cell hypoxia caused by mitochondrial dysfunction has become a hot research field.
      Sepsis damages the structure and function of mitochondria, conversely,
      mitochondrial dysfunction aggravated sepsis. The treatment of sepsis lacks
      effective specific drugs. The aim of this paper is to undertake a narrative
      review of the current experimental treatment for mitochondrial dysfunction in
      sepsis. The search was conducted in PubMed databases and Web of Science databases
      from 1950 to January 2014. A total of 1,090 references were retrieved by the
      search, of which 121 researches met all the inclusion criteria were included.
      Articles on the relationship between sepsis and mitochondria, and drugs used for
      mitochondrial dysfunction in sepsis were reviewed retrospectively. The drugs were
      divided into four categories: (1) Drug related to mitochondrial matrix and
      respiratory chain, (2) drugs of mitochondrial antioxidant and free radical
      scavengers, (3) drugs related to mitochondrial membrane stability, (4) hormone
      therapy for septic mitochondria. In animal experiments, many drugs show good
      results. However, clinical research lacks. In future studies, the urgent need is
      to develop promising drugs in clinical trials. 

PMID- 25983787
TI  - Continuous multiple vertebral compression fractures in multiple myeloma patient.
AB  - Multiple myeloma is a B-cell origin tumor characterized by hypercalcemia,
      osteolytic bony lesions, and pathologic fractures. Back pain is one of the most
      common presenting symptoms of multiple myeloma and about 60% of patients have
      vertebral involvement at the time of diagnosis7). Minimally invasive surgeries
      such as vertebroplasty and kyphoplasty are effective to relieve pain and improve
      the quality of life when a compression fracture occurs in multiple myeloma
      patients. We report a case of continuous multiple compression fractures
      associated with multiple myeloma. We should check for the possibility of
      pathologic vertebral fractures resulting from multiple myeloma in non
      osteoporotic compression fracture patients, and especially in cases of continuous
      fracture occurring in relatively non-elderly patients, even though a history of
      trauma may be present. 

PMID- 25983789
TI  - Metronidazole induced encephalopathy with peripheral polyneuropathy in patient
      with spinal cord injury.
AB  - Metronidazole may produce a number of neurologic side effects including
      peripheral neuropathy, seizure, encephalopathy. We experienced neurological side
      effects of metronidazole. The 32-year-old female patient with spinal cord injury
      was diagnosed as encephalophathy and peripheral polyneuropathy resulting from
      complication of metronidazole. It was difficult to diagnose at first glance using
      clinical findings because of paraplegia due to spinal cord injury. But through
      magnetic resonance imaging with diffusion weighted imaging and electrophysiologic
      study, the patient showed to have characteristic abnormalities that of a person
      suffering from metronidazole-induced encephalopathy and peripheral
      polyneuropathy. Whether the symptoms were caused by a peripheral nerve lesion or
      MIE, the patient's paraplegia prevented to appear other symptoms, such as ataxic
      gait and seizure, from manifesting. In such case as this, an active
      differentiated diagnosis is crucial. 

PMID- 25983792
TI  - Outcomes of Instrumented Posterolateral Fusion for Patients Over 70 Years with
      Degenerative Lumbar Spinal Disease: A Minimum of 2 Years Follow-up.
AB  - OBJECTIVE: To determine the outcome of posterolateral fusion (PLF) for patients
      over 70 years of age with degenerative lumbar spinal disease. METHODS: The
      authors reviewed 18 patients (13 women and 5 men) over 70 years of age who
      underwent PLF with a minimum 2-years follow-up at a single institution. The
      parameters for analysis were clinical outcome, intraoperative bleeding, operating
      time, transfusion amount, fusion rate, decreased disc height at the operated
      level, and the incidence of adjacent disc degeneration. RESULTS: The mean age and
      follow-up duration were 74.1 years and 44.7 months, respectively. The mean fusion
      level was 2.5 levels. 12 patients (66.7%) reported good or excellent outcomes,
      and 4 patients complained of poor outcomes. The fusion rate was 61.1%. The rate
      of adjacent segment degeneration was 61.1%. Among all of the patients, 5 had
      decreased intervertebral disc heights compared to their initial statuses. In
      correlative comparison analyses of parameters, a significant correlation was
      observed between a "good" or better clinical outcome and fusion (p=0.034). Also,
      there were significant relationships between a "fair" or better clinical outcome
      and fusion (p=0.045) and decreased disc height at the operated level (p=0.017).
      Other factors did not have a significant relationship with the clinical outcome.
      CONCLUSIONS: Before performing instrumented PLF in patients over 70 years old,
      problems related to the low fusion rate and adjacent segment degeneration should
      be considered and relevant information should be provided to the patients and the
      family.

PMID- 25983790
TI  - A novel blasted and grooved low profile pedicle screw able to resist high
      compression bending loads.
AB  - OBJECTIVE: Polyaxial pedicle screws are a safe, useful adjunct to transpedicular
      fixation. However, the large screw head size can cause soft tissue irritation,
      high rod positioning, and facet joint injury. However, the mechanical resistance
      provided by small and low profile pedicle screws is very limited. We therefore
      developed a novel, low profile pedicle screw using grooving and blasting
      treatment that is able to resist a high compression bending load. METHODS: We
      evaluated the compression bending force to displacement and yield loads for seven
      different screw head types that differed with regard to their groove intervals
      and whether or not they had been blasted. RESULTS: The rank order of screw types
      that had the greatest compression bending force to displacement was as follows:
      (1) universal polyaxial, (2) low polyaxial with 0.1mm grooves and blasting, (3)
      low polyaxial with blasting, (4) low polyaxial with 0.15mm grooves and blasting,
      (5) low polyaxial with 0.05mm grooves and blasting, (6) low polyaxial with 0.05mm
      grooves, (7) and low polyaxial. Low polyaxial screws with 0.1mm grooves and
      blasting had the maximum yield load and highest compression bending force to
      displacement of all seven polyaxial screw head systems evaluated. CONCLUSION:
      Blasting and grooving treatment of pedicle screw heads resulted in screw heads
      with a high yield load and compression bending force relative to displacement
      because of increased friction. Low polyaxial pedicle screws with 0.1 mm grooves
      treated by blasting have mechanical characteristics similar to those of universal
      polyaxial pedicle screws.

PMID- 25983793
TI  - Clinical efficacy of bone cement augmented screw fixation for the severe
      osteoporotic spine.
AB  - OBJECTIVE: Transpedicular instrumentation of the osteoporotic spine is a
      challenge for the spine surgeon due to the probability of screw loosening and the
      potential possibility of nonunion. The purpose of this study was to evaluate the
      clinical efficacy of bone cement augmented screw fixation in patients with severe
      osteoporosis. METHODS: Between February 2004 and August 2007, 250 patients with
      severe osteoporosis (T-score on BMD < -3.0) that had screw fixation were included
      in this study. The patients were divided into two groups (Group I: 157 patients
      that underwent bone cement augmented screw fixation that had a variety of spine
      spinal diseases including fractures, and Group II: 93 patients with severe
      osteoporosis that had screw fixation without bone cement augmentation). The
      imaging and clinical features were analyzed, including bone cement augmented
      levels, fusion rate and related complications. The visual analog scale (VAS),
      Oswestry disability questionnaire (ODI) and modified MacNab's criteria were used
      for the assessment of pain and functional capacity. RESULTS: In both groups, a
      significant improvement in the VAS and ODI was achieved. 146 out of 157 patients
      (93%) in Group I and 83 out of 93 patients (90%) in Group II were graded as an
      excellent or good result according to the modified MacNab's criteria. None of the
      patients experienced serious complications. However, there were two cases with
      neurological deterioration as a result of bone cement extravasation in Group I.
      For Group II, there were five cases of screw loosening that required re-operation
      for bone cement augmentation. CONCLUSION: Whether bone cement augmentation was
      performed or not, it was possible to achieve satisfactory results in patients
      with severe osteoporosis. However, if used carefully, bone cement augmented
      transpedicular screwing can reduce screw loosening and pullout in patients with
      severe osteoporosis.

PMID- 25983791
TI  - Comparative analysis of adjacent levels of degeneration and clinical outcomes
      between conventional pedicle screws and percutaneous pedicle screws in treatment
      of degenerative disease at l3-5; a preliminary report.
AB  - OBJECTIVE: This study was conducted to compare radiologic changes and clinical
      outcomes in adjacent level of percutaneous pedicle screws with those of
      conventional (open) pedicle screws. METHODS: From January 2007 to December 2009,
      51 patients underwent L3-5 decompression and spinal fusion. Percutaneous pedicle
      screws were used in 22 patients, and open pedicle screws were used in the
      remaining patients. For estimation of instability, we performed measurements of
      change in the lordotic and adjacent segment angles. A retrospective evaluation of
      the patients' data and several assessment scales was conducted for determination
      of clinical outcomes. RESULTS: The radiological examinations revealed no
      significant differences, except the L2-3 sagittal angle change. The upper
      adjacent level angle change in the open group was larger than that in the
      percutaneous group. In the percutaneous group, the sagittal angle changed from
      9.7+/-3.0 degrees  to 11.25+/-3.6 degrees  during the follow-up periods, and in
      the open group, the sagittal angle changed from 10.8+/-4.1 degrees  to 13.6+/-4.5
      degrees . Radiological instability was observed in 5 patients (17%) in the open
      group and in 2 patients (9%) in the percutaneous group. Both groups showed
      similar clinical outcomes. CONCLUSION: We suggest that open screws have a greater
      tendency to cause degenerative change in the upper segment than percutaneous
      screws. This may be because percutaneous screw fixation causes minimal injury to
      supporting structures and preserves adjacent facet joints.

PMID- 25983648
TI  - Search for decays of stopped long-lived particles produced in proton-proton
      collisions at [Formula: see text].
AB  - A search has been performed for long-lived particles that could have come to rest
      within the CMS detector, using the time intervals between LHC beam crossings. The
      existence of such particles could be deduced from observation of their decays via
      energy deposits in the CMS calorimeter appearing at times that are well separated
      from any proton-proton collisions. Using a data set corresponding to an
      integrated luminosity of 18.6[Formula: see text] of 8[Formula: see text] proton
      proton collisions, and a search interval corresponding to 281 h of trigger
      livetime, 10 events are observed, with a background prediction of [Formula: see
      text] events. Limits are presented at 95 % confidence level on gluino and top
      squark production, for over 13 orders of magnitude in the mean proper lifetime of
      the stopped particle. Assuming a cloud model of R-hadron interactions, a gluino
      with mass [Formula: see text]1000[Formula: see text] and a top squark with mass
      [Formula: see text]525[Formula: see text] are excluded, for lifetimes between 1
      [Formula: see text]s and 1000[Formula: see text]. These results are the most
      stringent constraints on stopped particles to date.

PMID- 25983794
TI  - Traumatic Atlanto-occipital Dislocation (AOD).
AB  - OBJECTIVE: Traumatic atlanto-occipital dislocation (AOD) results from high energy
      trauma and is an uncommon and usually fatal injury due to an injury to the
      cervicomedullary junction. Recently, improved prehospital management, early
      diagnosis and effective treatment led to increasing reports of survival. This
      study of patients with AOD initial imaging modalities recognizes the clinical
      features and diagnostic considerations for a quick diagnosis. METHODS: In this
      article, five survived adult patients with traumatic AOD are presented and
      retrospectively reviewed. Diagnosis was made by lateral cervical spine x-ray,
      cervical computed tomography (CT), or magnetic resonance imaging(MRI). Treatment
      consisted of early immobilization, respiratory support, and subsequent
      occipitocervical fusion. RESULTS: Four patients were male and the other one was
      female. Three were diagnosed early and the others were delayed in confirmations.
      One was type I AOD and four were type II AOD. All patients were applied
      occipitocervical fusion. Two cases were worse; neurological states and the other
      three that showed no change. Lateral X-ray film of all patients in the
      prevertebral soft tissue swelling at the C2 level was noted. The mean thickness
      of prevertebral soft tissue C2 level was 17.88 mm(15.18 to 20.17mm). Two were in
      the normal range of dens-basion index(DBI), three showed abnormalities, and
      Power's ratio was abnormal in 3 patients. CONCLUSION: As for damages caused by a
      strong external force in patients with severe prevertebral soft tissue swelling
      at C2 level abnormaly, the doctor determines whether more should be carefully AOD
      and considers 3D CT or MRI to confirm AOD in these patients.

PMID- 25983795
TI  - Single incision percutaneous pedicle screw fixation for transforaminal lumbar
      interbody fusion.
AB  - OBJECTIVE: Percutaneous pedicle screw fixation (PPSF) offers some of the
      advantages of minimally invasive surgery. However, an additional skin incision is
      necessary in order to gain these advantages. The author recently performed a
      modified PPSF through a single skin incision and it yielded good results. Here,
      we report the single incision percutaneous pedicle screw fixation (SIPPSF).
      METHODS: The medical records of 51 patients who underwent single segment
      transforaminal lumbar interbody fusion (TLIF) with pedicle screw fixation (PSF)
      between December 2009 and December 2011 were reviewed. The patients were divided
      into 3 groups according to the PSF technique used; conventional group (Group C),
      SIPPSF (Group S) and PPSF through multiple skin incisions (Group M). Operation
      time, estimated blood loss (EBL) and pain intensity before and after the
      operation using a numeric rating scale (NRS) were evaluated. RESULTS: The number
      of patients in Group S, Group C and Group M was 25, 17 and 9, respectively. The
      NRS demonstrated a reduction in pain intensity in all the patients, and there
      were no differences in NRS scoring between the three groups. Group S showed a
      reduction in the EBL compared to Group C (p=0.001) and a reduction in the
      operation time compared to Group M(p=0.003). CONCLUSION: The author supposes that
      the type of skin incision does not correlate significantly with the clinical
      results of TLIF with PPSF. However, it can be considered that SIPPSF offers the
      advantage of avoiding an additional paramedian skin incision.

PMID- 25983639
TI  - Measurement of distributions sensitive to the underlying event in inclusive Z
      boson production in [Formula: see text] collisions at [Formula: see text] TeV
      with the ATLAS detector.
AB  - A measurement of charged-particle distributions sensitive to the properties of
      the underlying event is presented for an inclusive sample of events containing a
      [Formula: see text]-boson, decaying to an electron or muon pair. The measurement
      is based on data collected using the ATLAS detector at the LHC in proton-proton
      collisions at a centre-of-mass energy of [Formula: see text] TeV with an
      integrated luminosity of [Formula: see text] fb[Formula: see text]. Distributions
      of the charged particle multiplicity and of the charged particle transverse
      momentum are measured in regions of azimuthal angle defined with respect to the
      [Formula: see text]-boson direction. The measured distributions are compared to
      similar distributions measured in jet events, and to the predictions of various
      Monte Carlo generators implementing different underlying event models.

PMID- 25983635
TI  - Search for contact interactions and large extra dimensions in the dilepton
      channel using proton-proton collisions at [Formula: see text] 8 TeV with the
      ATLAS detector.
AB  - A search is conducted for non-resonant new phenomena in dielectron and dimuon
      final states, originating from either contact interactions or large extra spatial
      dimensions. The LHC 2012 proton-proton collision dataset recorded by the ATLAS
      detector is used, corresponding to 20 fb[Formula: see text] at [Formula: see
      text] = 8 TeV. The dilepton invariant mass spectrum is a discriminating variable
      in both searches, with the contact interaction search additionally utilizing the
      dilepton forward-backward asymmetry. No significant deviations from the Standard
      Model expectation are observed. Lower limits are set on the [Formula: see text]
      contact interaction scale [Formula: see text] between 15.4 TeV and 26.3 TeV, at
      the 95 % credibility level. For large extra spatial dimensions, lower limits are
      set on the string scale [Formula: see text] between 3.2 TeV to 5.0 TeV.

PMID- 25983796
TI  - The effect of vertebroplasty on costal pain related to osteoporotic thoracic
      compression fractures in elderly patients.
AB  - OBJECTIVE: To analyze the effect of vertebroplasty on costal pain which develops
      following osteoporotic thoracic compression fractures (OTCFs). METHODS: The
      authors reviewed the medical records of 35 patients who underwent vertebral
      augmentation for the treatment of OTCFs over a five year period. The patients
      were divided into two groups: the costalgia group included patientswho had costal
      pain after a vertebral fracture and the non-costalgia group included patients
      without costalgia. To evaluate the effect of vertebroplasty on costal pain and
      factors related to costal pain, several factors including: vertebral body
      fracture type, pedicle injury, bone mineral density, the fracture level and
      clinical outcome were confirmed with magnetic resonance imaging and chart
      reviews. RESULTS: Among 35 patients, ten patients (28.6%) complained of costal
      pain with back pain. Only five of the ten patients (50%) had improved costal pain
      after a vertebroplasty. In the remaining 5 patients, the costal pain was improved
      through the use of medication including pain killers or a costal block during the
      follow-up period. Although the incidence of wedge deformity in the costal group
      was low(10%), there was no significant relationship to the incidence of costal
      pain statistically. Pedicle injury, bone mineral density and the fracture level
      had no significant relation to costal pain. CONCLUSION: The patients with wedge
      type, OTCFs may have a low incidence of costal pain as compared to those patients
      with bi-concave and crush deformities. The vertebroplasty effect on costal pain
      may not be effective. Therefore, before doing vertebroplasty, the surgeon should
      advise patients of this potential outcome in those treated for OTCFs.

PMID- 25983798
TI  - Horner Syndrome associated with a Herniated Cervical Disc: A Case Report.
AB  - Horner syndrome (HS) occurs when there is interruption of the oculosympathetic
      pathway. The causes of HS are various, but HS originated from herniated cervical
      disc is very few. HS attributable to the lesion of the first-order neuron of
      cervical spinal cord is extremely rare. A 41-year old male was admitted for
      sudden onset of left ptosis and right side numbness. Neurological examination
      revealed ptosis, miosis and facial anhidrosis on the left side. MRI and CT scans
      demonstrated large left paramedian disc herniation with cord compression at the
      C4-5 level. The herniated disc was removed through anterior approach and his
      symptoms were improved after the operation. 

PMID- 25983800
TI  - Discal cyst of the lumbar spine: a case report.
AB  - Discal cysts are a rare cause of lumbar radiculopathy. There are only a few
      reports of this disease in medical literature. The authors describe the case of a
      40-year-old man with a lumbar discal cyst that led to radiculopathy. An
      intraspinal extradural cystic mass was responsible for low and high signal
      intensities observed in lumbar lesions on T1 and T2 weighted magnetic resonance
      images. This cyst was a grossly spherical mass with clear serous fluid, which was
      connected to an adjacent intervertebral disc. Histopathology of the cystic walls
      revealed fibrous connective tissues without specific cell linings. Clinical
      symptoms were promptly relieved after surgical resection. Further research on the
      pathophysiology and treatment of discal cysts are needed. 

PMID- 25983802
TI  - Epilogue of Texas life.

PMID- 25983799
TI  - Immediate Revision Surgery due to Post-Anterior Cervical Discectomy and Fusion
      (ACDF) Spinal Epidural Hematoma.
AB  - Anterior cervical discectomy and fusion(ACDF) is a surgical treatment for
      cervical radiculopathy and myelopathy. Though this is a common surgery, spinal
      epidural hematomas occur rarely and an immediate treatment decision and surgical
      decompression are required in this situation. In this report, we discuss the
      proper treatment of spinal epidural hematoma after ACDF. 

PMID- 25983807
TI  - Lumbar disc screening using back pain questionnaires: oswestry low back pain
      score, aberdeen low back pain scale, and acute low back pain screening
      questionnaire.
AB  - OBJECTIVE: To evaluate the usefulness of back pain questionnaires for lumbar disc
      screening among Korean young males. METHODS: We carried out a survey for lumbar
      disc screening through back pain questionnaires among the volunteers with or
      without back pain. Three types of back pain questionnaire (Oswestry Low Back Pain
      Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screeing
      Questionnaire) were randomly assigned to the examinees. The authors reviewed
      lumbar imaging studies (simple lumbar radiographs, lumbar computed tomography,
      and magnetic resolutional images), and the severity of lumbar disc herniation was
      categorized according to the guidelines issued by the Korean military
      directorate. We calculated the relationship between the back pain questionnaire
      scores and the severity of lumbar disc herniation. RESULTS: The scores of back
      pain questionnaires increased according to the severity of lumbar disc
      herniation. But, the range of scores was very vague, so it is less predictable to
      detect lumbar disc herniation using only back pain questionnaires. The
      sensitivity between the back pain questionnaires and the presence of lumbar disc
      herniation was low (16-64%). CONCLUSION: Screening of lumbar disc herniation
      using only back pain questionnaires has limited value.

PMID- 25983806
TI  - The Correlation between Insertion Depth of Prodisc-C Artificial Disc and
      Postoperative Kyphotic Deformity: Clinical Importance of Insertion Depth of
      Artificial Disc.
AB  - OBJECTIVE: This study was designed to investigate the correlation between
      insertion depth of artificial disc and postoperative kyphotic deformity after
      Prodisc-C total disc replacement surgery, and the range of artificial disc
      insertion depth which is effective in preventing postoperative whole cervical or
      segmental kyphotic deformity. METHODS: A retrospective radiological analysis was
      performed in 50 patients who had undergone single level total disc replacement
      surgery. Records were reviewed to obtain demographic data. Preoperative and
      postoperative radiographs were assessed to determine C2-7 Cobb's angle and
      segmental angle and to investigate postoperative kyphotic deformity. A formula
      was introduced to calculate insertion depth of Prodisc-C artificial disc.
      Statistical analysis was performed to search the correlation between insertion
      depth of Prodisc-C artificial disc and postoperative kyphotic deformity, and to
      estimate insertion depth of Prodisc-C artificial disc to prevent postoperative
      kyphotic deformity. RESULTS: In this study no significant statistical correlation
      was observed between insertion depth of Prodisc-C artificial disc and
      postoperative kyphotic deformity regarding C2-7 Cobb's angle. Statistical
      correlation between insertion depth of Prodisc-C artificial disc and
      postoperative kyphotic deformity was observed regarding segmental angle (p<0.05).
      It failed to estimate proper insertion depth of Prodisc-C artificial disc
      effective in preventing postoperative kyphotic deformity. CONCLUSION:
      Postoperative segmental kyphotic deformity is associated with insertion depth of
      Prodisc-C artificial disc. Anterior located artificial disc leads to lordotic
      segmental angle and posterior located artificial disc leads to kyphotic segmental
      angle postoperatively. But C2-7 Cobb's angle is not affected by artificial disc
      location after the surgery.

PMID- 25983803
TI  - Finite element analysis of the biomechanical effect of coflexTM on the lumbar
      spine.
AB  - OBJECTIVE: The biomechanical properties of the CoflexTM (Paradigm Spine, NY,
      USA), a device designed to provide dynamic stabilization without lumbar fusion,
      have not been clearly defined. The purpose of this study was to determine the
      efficacy and biomechanical effect of CoflexTM using finite element model (FEM).
      METHODS: A 3D geometric model of the L3-L5 was created by integrating
      computerized tomography (CT) images. Based on the geometric model, a 3D FEM was
      created and the CoflexTM model was incorporated into the base model. Mechanical
      load dependent on the postural changes and boundary conditions, were imposed to
      simulate various 3D physiological states. The simulation analysis included stress
      and strain distributions, intervertebral disc deformation, and the range of
      motion of the facet joint and lumbar spinous process. RESULTS: CoflexTM
      significantly restrained displacement in extension, lateral bending and
      compression of joint between the L4-5 as one in the experimental group was
      observed -1.3% of flexion, -24.5% of extension, -44.5% of lateral bending and 
      37.2%. The average intradiscal pressure of the L4-5 decreased by 63% and the
      average facet contract force of the L4-5 decreased markedly by 34% in the
      experimental group. A load of 120 MPa from extension was observed at the base of
      spinous process in the experimental group. CONCLUSION: The CoflexTM can be safely
      used for achieving functional dynamic stabilization of the lumbar vertebral
      column while preserving the intactness of the other components. However, the
      fatigue fracture of the L4 spinous process should be carefully monitored.

PMID- 25983801
TI  - Cavernous hemangioma occurred between the trapezius and splenius capitis muscle.
AB  - Hemangiomas are the most common benign tumor of soft tissue. They are frequently
      seen on the trunk and extremities. In addition, most of them exist at the skin
      and subcutaneous layer, but fewer than 1% does in the intramuscular layer. For
      the diagnostic images of the intramuscular cavernous hemangioma, ultrasound (US),
      computed tomography (CT) and magnetic resonance imaging (MRI) are used currently.
      Multiple therapeutic methods are used, but surgical excision is considered as the
      most ideal treatment. We describe the recurred cavernous hemangioma occurred
      between the trapezius and splenius capitis muscle. The mass was well demarcated
      but scattered and infiltrated into the adjacent muscle layer, therefore,
      extensive resection was unavoidable. When determining a treatment regime for the
      hemangioma, it is essential to consider the size of the mass, cosmetic and
      functional aspects of the patient. 

PMID- 25983797
TI  - Long-term Follow-up (Minimum 5 Years) Study of Single-level Posterior Dynamic
      Stabilization in Lumbar Degenerative Disease; 'Interspinous U' & 'DIAM'.
AB  - OBJECTIVES: Recently posterior dynamic stabilizations (PDS) are increased in
      degenerative lumbar disease. But, some previous studies had doubts its long term
      prognosis. Long term clinical and radiological results of PDS using interspinous
      device (Interspinous U, DIAM) were analyzed. METHODS: We have used the
      'interspinous U' and 'DIAM' for patients with lumbar spinal stenosis. We included
      single level lumbar spinal stenosis patients who completed minimum 60 months
      follow-up evaluation. All patients checked plain lateral and flexion-extension
      views at immediately after the surgery and each follow-up. The clinical outcome
      was measured by Odom's criteria. Complications including post operative
      infection, bony erosion, device fracture, device malformations, and instabilities
      were surveyed. RESULTS: We included 18 for 'Interspinous U' and 7 patients 'DIAM'
      groups. Mean follow-up durations for 'Interspinous U' and 'DIAM' were 74.6 and
      62.6 months, respectively. Satisfactory groups were 50.0% and 42.9 % for
      'Interspinous U' and 'DIAM' groups. In 'Interspinous U' group disc height ratio
      increased transiently in immediate postoperative period (from 0.18 to 0.21) and
      then, decreased significantly in last follow-up (0.18). In 'DIAM' group, disc
      height ratio increased transiently in immediate postoperative period (from 0.18
      to 0.19), and then decreased significantly in the last follow-up (0.16). Three
      (16.7%) and two (28.6%) patients undergo on a re-operation due to severe back
      pain in 'Interspinous U' and 'DIAM' groups. CONCLUSION: Long term follow up
      'Interspinous U' and 'DIAM' group showed low patient satisfaction and poor
      radiological outcomes. To ascertain the benefit of PDS compare with posterior
      screw fixation, prospective analysis with larger population and multi-center
      study will be needed.

PMID- 25983811
TI  - Correction of Coronal Imbalance in Degenerative Lumbar Spine Disease Following
      Direct Lateral Interbody Fusion (DLIF).
AB  - OBJECTIVE: The authors have recently been using a surgical technique of minimally
      invasive direct lateral interbody fusion (DLIF) for correcting of coronal
      imbalance. The purpose of this study was to evaluate the surgical outcome and
      complication of DLIF. METHODS: We undertook retrospective analysis of a
      consecutive series of 8 DLIF procedures in Degenerative lumbar spine disease
      since May 2011. Four patients underwent DLIF only, and the others underwent
      combined DLIF and posterior fixation. Data on intra- and postoperative
      complications were collected. The pre- and postoperative X-rays were reviewed. We
      investigated coronal deformity, Cobb's angle, and apical vertebral translation
      (AVT). The mean follow-up period was months with a range of 2 to 8 months.
      RESULTS: A mean preoperative coronal Cobb's angle was 21.8 degrees  (range 11.5
      32.4 degrees ). Following after DLIF, the mean Cobb's angle was decreased to 13.0
      degrees  (range 2.9-21.5 degrees ). Following additional posterior screw
      fixation, mean Cobb's angle was further decreased to 7.4 degrees  (range 2.9-13.2
      degrees ). A mean preoperative AVT was 2.0 cm(range 0.6-3.5 cm), and improved to
      1.4 cm(range 0.3-2.4 cm) and 0.8 cm(range 0.2-1.8 cm) postoperatively (DLIF and,
      posterior fixation respectively). One patient (12.5%) showed cage migration
      during follow-up period. Two patients (25%) developed motor weakness, and 4
      patients (50%) experienced postoperative thigh paresthesias or dysesthesias.
      During follow up period, motor weakness had resolved in 1 patient. Sensory
      symptoms were improved in all patients at the last follow-up. CONCLUSION:
      Degenerative lumbar disease can be effectively corrected by DLIF with acceptable
      complications.

PMID- 25983814
TI  - Cervical expansive laminoplasty with 90 degrees  box-shape double door method.
AB  - OBJECTIVE: The aim of this study is to introduce the surgical method with
      miniplate and compared the expansion rate of the spinal canal area with other
      kinds of lamina spacers. METHODS: Between June. 2008 and May 2011, we performed
      expansive cervical laminoplasty on 61 patients. We analyzed the results of these
      operations, examining type of lamina spacer used, spinal canal areas between pre-
      and postoperative CT scans, and operative methods. RESULTS: 39 patients were
      analyzed retrospectively. Miniplates were used in 21 patients with 103 levels.
      Hydroxyapatite (HA) was used in 6 patients with 29 levels, and Centerpiece(r) was
      used in 12 patients with 54 levels. The expansion area was calculated using
      Photoshop CS3(r). The expansion rate of the miniplates was 76.5%, that of HA was
      49.8%, and that obtained with Centerpiece was 50.6%. The excellent 90 degrees 
      box-shaped widening of the laminae achieved through the surgery can be checked
      easily by AP X-ray. All miniplates are positioned horizontally and parallel, and
      the lamina is seen as a pedicle of thoracic or lumbar spine due to its 90 degrees
      erect position. Neurologic improvement and clinical outcomes will be discussed.
      No complications were reported with miniplates. CONCLUSION: Box-shaped
      laminoplasty with miniplates is the widest spinal canal expansion method among
      the three types of implants examined.

PMID- 25983813
TI  - Initial clinical outcomes of minimally invasive lateral lumbar interbody fusion
      in degenerative lumbar disease: a preliminary report on the experience of a
      single institution with 30 cases.
AB  - OBJECTIVE: The object of this study was to evaluate the clinical and radiological
      outcomes of minimally invasive lateral lumbar interbody fusion. METHODS: This
      study included 30 patients who underwent minimally invasive lateral lumbar
      interbody fusion at our hospital between May 2011 and February 2012 for the
      following diagnoses: degenerative disc disease, adjacent-segment degeneration,
      degenerative spondylolisthesis and lumbar degenerative scoliosis. Pain assessment
      was reported from 0 to 10 using a subjective visual analog scale (VAS) upon
      admission and at every follow-up day. Lumbar X-rays were obtained in the standing
      position upon admission and the 1st and 5th postoperative day, and at every
      follow-up day after the operation. The heights of the intervertebral disc space
      and neural foramen were measured using an electronic caliper with the PACS
      software. The surgical outcome was assessed as excellent, good, fair or poor
      using the Odom scale at the last follow-up. RESULTS: The mean VAS for low back
      pain were 4.93+/-1.47 on admission and 2.01+/-1.35 at last follow-up,
      respectively, and for leg pain, the scores were 4.87+/-2.16 on admission and
      1.58+/-1.52 at last follow-up. The mean height of intervertebral disc space
      increased by 34% (7.93+/-2.33 preoperatively, and 11.09+/-4.33 immediately after
      surgery, p<0.01). The mean height of neural foramen also increased by 6.4%
      without any statistical significance (19.17+/-2.84 preoperatively, and 20.49+/
      4.50 immediately after the surgery). Minimally invasive lateral lumbar interbody
      fusion was successful in 27 patients (90%) at last follow-up. Surgical
      complications were reported as transient postoperative thigh sensory changes (5
      patients, 16.7%), transient psoas muscle weakness (3 patients, 10%), cage
      migration (2 patients, 6.7%), lumbar plexus injury (1 patient, 3.3%), and pain
      aggravation (1 patient, 3.3%). CONCLUSION: The minimally invasive lateral lumbar
      interbody fusion is a safe and effective procedure for treating degenerative
      lumbar disease with good outcomes and moderate complications. Further follow-up
      is necessary to establish its safety and efficacy.

PMID- 25983804
TI  - Radiological Efficacy of Cervical Lateral Mass Screw Insertion and Rod Fixation
      by Modified Magerl's Method (Yoon's Method) with Minimum 2 Years of Follow-up.
AB  - OBJECTIVE: Cervical lateral mass screw insertion and rod fixation is a useful
      method for stabilizing the cervical disease, so various modified techniques were
      present. Many surgeons had reported the biomechanical safety according to the
      screw positioning method in the cervical spine, but the modified Magerl's method
      (Yoon's method) was not well studied. So, this study assessed the radiological
      efficacy of the modified Magerl's method with long-term follow-up. METHODS: This
      study retrospectively reviewed 323 lateral mass screws of 50 patients who had
      followed-up at least 2 years. Radiologic data were analyzed as parameters of
      complications after operation, including kyphotic or lordotic change, bone
      fusion, pull-out or malposition of screw, foraminal stenosis, adjacent disc
      degeneration or aggravation, pseudoarthrosis, and vertebral artery injury.
      RESULTS: The mean follow-up period was 32 (24 to 52) months. There were kyphotic
      changes in 4.0%(2 of 50 cases). Unsuccessful bone fusion occurred in 4.0%(2 of 50
      cases). Among the 323 screws, screw pull-out (4.0%. 2 of 50cases, 3 of 323
      screws), foraminal invasion (1.2% of total screws), and facet injury (0.6% of
      total screws) occurred. CONCLUSION: The lateral mass screw insertion and rod
      fixation by the modified Magerl's method (Yoon's method) is a safe and reliable
      technique with low rate of complication related to instruments in minimum 2 years
      follow-up.

PMID- 25983812
TI  - Comparative Study between a Curved and a Wedge PEEK Cage for Single-level
      Anterior Cervical Discectomy and Interbody Fusion.
AB  - OBJECTIVE: This study evaluated the efficiency of a curved polyetheretherketone
      (PEEK) cage in comparison with a wedge PEEK cage according to radiologic and
      clinical outcomes in patients with cervical degenerative disease. METHODS: A
      total of 37 patients who suffering from cervical disc disease with radiculopathy
      or myelopathy were reviewed retrospectively. Seventeen patients were underwent
      anterior cervical discectomy and interbody fusion with a curved shape PEEK cage
      (curved cage group), and twenty patients with wedge shape PEEK cage (wedge cage
      group). Clinical assessment was graded using Odom's criteria, NDI score and VAS
      score. For radiologic analysis, disc height (DH), segmental angle (SA),
      subsidence were measured at the preoperative and last follow up. RESULTS: A
      comparison of the preoperative and postoperative results revealed improvements
      after the surgery in the DH and SA in both cage groups. The change of
      postoperative DH between the preoperative and the last follow-up in wedge cage
      group and curved cage group was 6.85% and 25.5%, respectively. The change of
      postoperative SA was 1.75 degrees  and 0.95 degrees , respectively. There was no
      statistically significant difference in the DH and SA between the 2 groups. The
      subsidence rate in the wedge cage group and curved cage group was 20% and 6%,
      respectively. CONCLUSION: The 2 different cage groups showed significant
      improvements in the disc height, segmental angle and clinical outcomes. However,
      the shape of PEEK Cage influences the tendency for subsidence. Increasing contact
      surface area and fitting into two adjacent vertebral body prevent significant
      subsidence.

PMID- 25983808
TI  - Percutaneous Disc Coagulation Therapy (PDCT) comparing with Automated
      Percutaneous Lumbar Discectomy (APLD) in Patients of Herniated Lumbar Disc
      Disease: Preliminary Report.
AB  - OBJECTIVE: Percutaneous techniques are rapidly replacing traditional open
      surgery. This is a randomized controlled trial study of clinical outcomes of
      Percutaneous Plasma Disc Coagulation Therapy (PDCT) in patients with
      HLD(herniated lumbar disc) as a new percutaneous access in comparison with
      Automated Percutaneous Lumbar Discectomy (APLD) in its clinical application and
      usefulness as a reliable alternative method. METHODS: The authors analyzed 25
      patients who underwent PDCT randomized 1:1 to 25 who underwent APLD between June,
      2010 and October, 2011. All patients had herniated lumbar disc diseases. The
      clinical outcomes were evaluated using Visual Analog Scales (VAS) score and
      MacNab's criteria. RESULTS: The age of the patients who underwent PDCT ranged
      from 29 to 88 years with a mean age of 51.8 years. The age of the APLD undergone
      patients' population ranged from 30 to 66 with a mean age of 46.0 years. The
      average preoperative VAS score in PDCT was 7.60 and 1.94 at 7months post
      operatively, and in APLD was 7.32, and 3.53 at 7 months post-operatively
      (p<0.001). In Macnab's criteria, 20 patients (80%) had achieved favorable
      improvement (excellent and good) in PDCT group. In Macnab's criteria, 16 patients
      (64%) had achieved favorable improvement in APLD group (p<0.001). CONCLUSION:
      PDCT can be considered a viable option as a new percutaneous access to herniated
      lumbar disc. PDCT showed to be more effective than APLD in this study, allowing
      stable decompression and safe minimally invasive operation to an area desired by
      the operator in lumbar disc herniation patients, although further long term
      clinical evaluations are still necessary.

PMID- 25983805
TI  - An early comparative analysis of the use of autograft versus allograft in
      anterior cervical discectomy and fusion.
AB  - OBJECTIVE: The purpose of this study is to verify the usefulness of autograft
      versus allograft in the radiographic and clinical outcome in early period after
      the surgery. METHODS: We performed a retrospective review of 38 patients who had
      undergone one- or two-level anterior cervical discectomy and fusion (ACDF) with
      rigid anterior plate fixation from March 2006 to May 2009. Interbody graft
      materials were iliac autograft (n=17) or with allograft (n=21). Fusion rate and
      graft collapse rate were assessed by radiographic analysis and clinical outcome
      was based on Odom's criteria. RESULTS: In autograft group, 13 patients achieved
      successful bone fusion (65%), whereas 7 patients (31.8%) in allograft group.
      There was statistically significant between two groups (p<0.05). Comparing
      immediate postoperative radiograph with last follow-up, the mean graft collapse
      was noted 1.3mm(15.5% change) in autograft group, whereas 2.0mm(24.7% change) in
      allograft group. There was no statistically significant collapse rate in
      autograft group (p>0.05), but statistically significant in allograft group
      (p<0.05). Clinical outcome was excellent or good in 94.1% in autograft group, and
      90.5% in allograft group. CONCLUSION: In study, anterior cervical interbody
      fusion with an allograft got a result of lower fusion rate and higher collapse
      rate compared with autograft in early period after surgery, and clinical outcome
      showed similar results in both groups.

PMID- 25983809
TI  - A PET/CT-based Morphometric Study of Spinal Canal in Korean Young Adults:
      Anteroposterior Diameter from Cervical Vertebra to Sacrum.
AB  - OBJECTIVE: To establish normative data for spinal canal AP diameter from cervical
      vertebra to sacrum in the Korean young and to assess the exposed spinal canal
      after laminectomy which was related with restenosis by post-laminectomy membrane
      formation. METHODS: From PET/CT, axial bone-window CT of 83 young adults (20-29
      years) were obtained, and we measured AP diameters of C3, C5, C7, T1, T4, T8,
      T12, L1, L3, L5 and S1. We also measured exposed AP diameter of C3, C5, C7, T1
      and T2 above imaginary line for laminectomy. RESULTS: The shortest mean AP
      diameter was at C5 (14.5+/-1.5 mm), and the longest was at S1 (17.4+/-2.3 mm). AP
      diameter increased from C3 (14.6+/-1.1 mm) to T1 (16.1+/-1.2 mm) at cervical
      spine. In the thoracic spine, the diameter gradually decreased from T1 (16.1+/
      1.2 mm) to T8 (14.6+/-1.3 mm) and increased to T12 (16.7+/-1.2 mm). The diameter
      decreased from L1 (16.7+/-1.3 mm) to L3 (15.7+/-1.9 mm), and it increased to S1
      (17.4+/-2.3 mm) at lumbar spine. Exposed AP diameter above imaginary line for
      laminectomy was the longest at C3 (4.8+/-1.2 mm) and gradually decreased to T1
      (3.3+/-0.9 mm) and T2 (0 mm). CONCLUSIONS: Spinal AP diameter was the shortest in
      the mid-cervical area (C5) and increased to the upper thoracic area. From the
      upper thoracic vertebra, the diameter gradually decreased to the mid-thoracic
      vertebra (T8) and then increased to the lower thoracic vertebra. Lumbar vertebra
      also was similar with thoracic vertebra. Below T2, there was no exposed dural sac
      after laminectomy. This means that restenosis by post-laminectomy membrane
      formation can occur above T1.

PMID- 25983810
TI  - Surgical results and risk factors for recurrence of lumbar disc herniation.
AB  - OBJECTIVE: Recurrent lumbar disc herniation has been defined as disc herniation
      at the same level, regardless of ipsilateral or contralateral herniation, with a
      pain-free interval greater than 6 months. The aim of this study is to analyze
      outcomes and identify the potential risk factors for recurrent lumbar disc
      herniation. METHODS: The authors retrospectively reviewed the cases of 178
      patients who underwent open discectomy for single-level lumbar disc herniation.
      Visual analogue scales and modified Macnab criteria were used to compare the
      clinical outcomes between the recurrent group and the non-recurrent group. Sex,
      age, discectomy level, degree of disc degeneration, type of disc herniation, pain
      free interval after first-operation, smoking status, and trauma were investigated
      as potential recurrence risk factors. RESULTS: Of the 178 patients for whom the
      authors were able to definitely assess symptomatic recurrence status, 18 patients
      (10.1%) underwent revision surgery for recurrent disc herniation. The most common
      level involved was L4-L5 (61%) and the mean period of time to recurrence was 18.7
      months (6-61 months). There were 17 cases of ipsilateral herniation and 1 case of
      contralateral herniation. The types of herniation for which revision surgery was
      done were protrusion (3 cases), and transligamentous extrusion (14 cases). There
      were five excellent, eight good, and two fair results. CONCLUSION: Repeated
      discectomy for recurrent disc herniation produced unsatisfactory outcomes.
      Factors such as sex, type of disc herniation and traumatic events were found to
      be significant risk factors.

PMID- 25983819
TI  - Unrecognized shoulder disorders in treatment of cervical spondylosis presenting
      neck and shoulder pain.
AB  - OBJECTIVE: Cervical spondylosis and shoulder disorders share with neck and
      shoulder pain. Differentiating between the two can be challenging and patient
      with combined pathologies is less likely to have pain improvement even after
      successful cervical operation. We investigated clinical characteristics of the
      patients who were diagnosed as cervical spondylosis however, were turned out to
      have shoulder disorders or the patients whose pain was solely originated from
      shoulder. METHODS: Between January 2008 and October 2009, the patients presenting
      neck and shoulder pain with diagnosis of cervical spondylosis were enrolled.
      Among them, the patients who met following inclusion criteria were grouped into
      shoulder disorder group and the others were into cervical spondylosis group.
      Inclusion criteria were as follows. (1) To have residual or unresponsive neck and
      shoulder pain despite of optimal surgical treatment due to concomitant shoulder
      disorders. (2) When the operation was cancelled for the reason that shoulder and
      neck pain was proved to be related with unrecognized shoulder disorders. The
      authors retrospectively reviewed and compared clinical characteristics, level of
      pathology, diagnosis of cervical spondylosis and shoulder disorders. RESULTS: A
      total of 96 patients were enrolled in this study. Shoulder disorder group was
      composed of 15 patients (15.8%) and needed additional orthopedic treatment.
      Cervical spondylosis group was composed of 81 patients (84.2%). There was no
      significant differences in mean age, sex ratio and major diagnosis in both
      shoulder disorder and cervical spondylosis group (p=0.33, 0.78, and 0.68
      respectively). However, the distribution of pathologic levels was found to be
      significantly different (p=0.03). In shoulder disorder group, the majority of
      lesions (15 of 19 levels, 78.9%) were located at the level of C4-5 (36.8%) and C5
      6 (42.1%). On the other hand, in cervical spondylosis group, C5-6 (39.0%) and C6
      7 (37.1%) were the most frequently observed level of lesions (80 of 105 levels,
      16.1%). CONCLUSION: It is very important for spine surgeons to perform a complete
      history taking and physical examination using the special tests, and to discover
      the underlying shoulder disorders causing of symptom in treatment of cervical
      spondylosis presenting neck and shoulder pain.

PMID- 25983816
TI  - Diagnosis of Cervical OPLL in Lateral Radiograph and MRI: Is it Reliable?
AB  - OBJECTIVE: Cervical OPLL is a relatively common cause of developing cervical
      myelopathy or radiculopathy in Asians. Cervical OPLL is sometimes missed in
      lateral radiography or MRI. In the present study, we analyzed the diagnostic
      accuracy of cervical OPLL in lateral radiography and MRI compared to CT scan.
      METHODS: This is a retrospective study of forty-six patients who underwent
      decompressive surgery anteriorly or posteriorly in our institute. All patients
      were diagnosed with cervical OPLL by CT scan. The patients were grouped into
      continuous type, segmental type, mixed type, and localized type. We then
      evaluated lateral radiographs and MRI compared to CT scans. The diagnostic
      accuracy and false negative rates in lateral radiograph and MRI were evaluated.
      RESULTS: In a total of 46 patients diagnosed with cervical OPLL in CT scans,
      diagnostic accuracy using lateral radiograph and MRI were 52.2%(24/46) and
      58.7%(27/46), respectively. In the continuous type group, diagnostic accuracy
      using lateral radiograph and MRI were 85.7%(6/7) and 100.0%(7/7). In the
      segmental type group, diagnostic accuracy using lateral radiograph and MRI were
      27.3%(6/22) and 31.8%(7/22). In the mixed type group, diagnostic accuracy was
      91.7%(11/12) in lateral radiograph and 83.3%(10/12) in MRI. In the localized
      group, diagnostic accuracy was 20.0%(1/5) in lateral radiograph and 60.0%(3/5) in
      MRI. CONCLUSION: The diagnostic accuracy of cervical OPLL using lateral
      radiograph and MRI was less than using CT scan. For the best treatment plan,
      preoperative CT scan should be performed to detect conditions of ossifications
      such as cervical OPLL.

PMID- 25983815
TI  - Comparisons of Two-level Discectomy and Fusion with Cage Alone versus Single
      level Corpectomy and Fusion with Plate in the Treatment of Cervical Degenerative
      Disc Disease.
AB  - OBJECTIVE: To compare the radiologic parameters and clinical outcomes of two
      level anterior cervical discectomy and fusion (ACDF) with cage alone versus
      single-level anterior cervical corpectomy and fusion (ACCF) with plate in the
      treatment of two-level contiguous cervical degenerative disc disease. METHODS: Of
      all 38 consecutive patients who were included in this study, 22 patients
      underwent on a two-level contiguous ACDF with cage alone (ACDF-CA group), 16
      patients underwent a single-level ACCF with plate (ACCF-P group). We compared
      following parameters between these two groups; perioperative parameters (hospital
      stays, blood loss and operation duration), clinical parameters (Japanese
      Orthopedic Association scores and Odom's criteria) and radiologic parameters
      segmental height ratio (SHR), segmental lordotic angle (SLA), global lordotic
      angle (GLA) and fusion rate). RESULTS: The amount of operative blood loss in the
      ACCF-P group was higher than in the ACDF-CA group with statistical significance
      (p<0.05). Clinical outcomes and fusion rates were similar between groups. The
      postoperative SHRs in both groups were higher than that of preoperative period
      with statistical significance; however, these values significantly decreased at
      the last follow up period. The SLA increased during the immediate postoperative
      period, and then mild decreased. The values of GLA in both groups did show
      variable differences according to each time frame. CONCLUSION: The results of
      ACDF-CA were comparable with ACCF-P with regard to clinical and radiologic
      outcomes in contiguous two-level cervical fusion. A two-level ACDF-CA as a
      treatment modality for two-level contiguous cervical disc disease may be a
      worthwhile method as an alternative to single-level ACCF-P.

PMID- 25983818
TI  - Comparative Study of the Outcomes of Percutaneous Endoscopic Lumbar Discectomy
      and Microscopic Lumbar Discectomy Using the Tubular Retractor System Based on the
      VAS, ODI, and SF-36.
AB  - OBJECTIVE: Percutaneous endoscopic lumbar discectomy (PELD) and microdiscectomy
      with the microscope endoscopic tubular retractor system(METRx-MD) are considered
      popular minimally invasive surgery (MIS) methods for the treatment of lumbar disc
      herniation. Many authors have also reported good clinical outcomes of these
      methods, but there are few comparative studies of them. This report compares the
      clinical outcomes of PELD and METRx-MD for lumbar disc herniation as MIS methods
      and discusses the efficacy of PELD. METHODS: Seventy-two patients who had
      undergone single-level unilateral discectomy using two different methods, PELD
      and METRx-MD, between 2009 and 2011 were given a follow-up examination
      prospectively. Thirty-seven of these patients underwent discectomy using PELD,
      and the remaining 35 patients underwent discectomy using METRx-MD. In addition to
      the general parameters, clinical outcomes were assessed as specific parameters
      using the Visual Analogue Scale (VAS) score, the Oswestry Disability Index (ODI),
      the Short-form 36 (SF-36), and the return-to-work time. RESULTS: Sixty-seven
      percent (25/37) of the patients in the PELD group and 74%(26/35) in the METRx-MD
      group were included in follow-up more than 6 months post-operatively. The mean
      improvements in the VAS scores for the back pain, leg pain, and ODI were 2.6,
      4.8, and 30.1% for the PELD group and 2.8, 4.6, and 33.2% for the METRx-MD group,
      respectively. The SF-36 physical health component subscale score improved from
      40.6 pre-operatively to 68.3 at the last follow-up for the PELD group post
      operatively, and from 48.5 to 65.1 in the mental component subscale (METRx-MD
      group: from 34.4 to 66.5 and from 44.87 to 56.7). Complications occurred in 3/37
      patients in the PELD group and in 2/35 patients in the METRx-MD group in the peri
      operative period. The mean return-to-work times were 37.5 days in the PELD group
      and 42.5 days in the METRx-MD group. CONCLUSION: The outcomes for the PELD group
      are comparable to those for the METRx-MD group. It can thus be concluded that
      PELD for lumbar disk herniations may be performed safely and effectively. Also,
      PELD can be considered one of the treatment modalities of lumbar disk herniation.

PMID- 25983817
TI  - Heterotopic ossification following cervical total disc replacement: iatrogenic or
      constitutional?
AB  - OBJECTIVE: To elucidate etiological factors of heterotopic ossification (HO) by
      evaluating retrospectively if HO is a unique finding following cervical total
      disc replacement (CTDR) or a finding observable following an anterior cervical
      interbody fusion (ACIF). METHODS: The authors had selected 87 patients who
      underwent anterior cervical surgery (TDR or ACIF), and could be followed up more
      than 24 months. A cervical TDR was performed using a Bryan disc or a ProDisc-C
      and an ACIF using a stand-alone cage or fibular allograft with a plate and screws
      system. The presence of HO was determined by observing plain radiography at the
      last follow up. The relation between HO occurrence and specific preoperative
      radio-logical findings (osteophyte and calcification of posterior longitudinal
      ligament (PLL)) at the index level was investigated. RESULTS: Cervical TDR was
      performed in 40 patients (43 levels) and ACIF in 47 patients (54 levels). At the
      final radiographs, HO was demonstrated at 27 levels (TDR-Bryan; 8/18, TDR-Prodisc
      C; 12/25, ACIF-cage alone; 7/29, and ACIF-plate screw; 0/25). Mean ROM at the
      last follow-up of each TDR subgroup were 7.8+/-4.7 degrees  in Bryan, 3.89+/-1.77
      degrees  in Prodisc-C, and it did not correlated with the incidence of HO. Fusion
      status of ACIF groups was observed as 2 case of grade 1, 6 of grade 2, and 21 of
      grade 3 in cage alone subgroup, and no case of grade 1, 4 of grade 2, and 21 of
      grade 3 in plate screw subgroup. Fusion status in ACIF-cage alone subgroup was
      significantly related to the HO incidence. The preoperative osteophyte at the
      operated level observed in 27 levels, and HO was demonstrated in 12 levels (TDR
      Bryan; 3/5, TDR-Prodisc-C; 2/3, ACIF-cage alone; 7/11, and ACIF-plate screw;
      0/8). Preoperative PLL calcification at the operated level was observed 22
      levels, and HO was defined at 14 levels (TDR-Bryan; 5/5, TDR-Prodisc-C; 4/5, ACIF
      cage alone; 5/7, and ACIF-plate screw; 0/5). The evidence of preoperative
      osteophyte and PLL calcification showed statistically significant relations to
      the occurrence of HO. CONCLUSION: HO was observed in both TDR and ACIF groups. HO
      was more frequently occurred in TDR group regardless of prosthesis type. In ACIF
      group, only cage alone subgroup showed HO, with relation to fusion status.
      Preoperative calcification of longitudinal ligaments and osteophyte were strongly
      related to the occurrence of HO.

PMID- 25983820
TI  - Usefulness of SPAIR Image, Fracture Line and the Adjacent Discs Change on
      Magnetic Resonance Image in the Acute Osteoporotic Compression Fracture.
AB  - OBJECTIVE: Osteoporotic compression fracture is an increasing issue in this
      community and its diagnosis depends on the magnetic resonance images (MRI).
      Although T1- and T2-weighted images (T1WI and T2WI) have high sensitivity and
      specificity, the fat suppression technique gives more clear delineation of this
      abnormalities. Accordingly, we re-evaluated its exact sensitivity and specificity
      for the imaging diagnosis of osteoporotic compression fractures in our cases. For
      additional information about the osteoporotic compression fractures, we evaluate
      the fracture lines, fluid sign and adjacent discs change on the MRI. METHODS:
      Retrospectively, total 85 patients who had been diagnosed with acute osteoporotic
      compression fracture were enrolled. They all had been underwent MRI including
      T1WI, T2WI and T2-Spectral Adiabatic Inversion Recovery (SPAIR) sequence.
      RESULTS: In this study, the incidence of high signal intensity on T2-SPAIR image
      was very high (0.9917). The fluid sign was seen in 56.7% on the SPAIR image. The
      fracture lines were more observed on the T2WI than T1WI (p=0.0062). The adjacent
      discs change on T2WI and T2-SPAIR image were higher than T1WI (p<0.001).
      CONCLUSION: For the acute osteoporotic compression fracture, T2-SPAIR image is
      the most specific sequence of the all sequences. The fluid sign is another
      suggestive finding when considered other studies. T2WI is more useful to find the
      fracture line than T1WI. Abnormal signal intensity on the adjacent discs may
      provide additional information for the acute osteoporotic compression fractures.

PMID- 25983821
TI  - Surgical results after unilateral laminectomy for the removal of spinal cord
      tumors.
AB  - OBJECTIVE: To reduce the risk of postoperative spinal instability or deformity,
      unilateral laminectomy (UL) has been recommended to remove spinal space-occupying
      lesions. The purpose of this study was to determine whether there were any
      advantages of UL for removal of spinal cord tumors. METHODS: From May 1995 to May
      2010, 94 patients with spinal cord tumors, who underwent tumor removal via UL in
      our institute, were enrolled in this study. Intramedullary spinal cord tumors
      were excluded. Simple radiographs were obtained for accessing the restoration of
      the spinal column. Spinal magnetic resonance imaging (MRI) was also obtained
      during the follow-up period to evaluate tumor recurrence. RESULTS: There were 51
      women and 43 men; their mean age was 47.8 years (range, 9-83 years). The mean
      follow-up period was 52.6 months (range, 24 month-16 years). The sites of the
      tumors were cervical in 21 cases, thoracic in 37, lumbar in 33, and sacral in 3.
      These cases included 85 intradural extramedullary (IDEM) and 9 extradural (ED)
      lesions. IDEM tumors consisted mainly of neurilemmomas (56.3%) and meningiomas
      (22.3%).Tumors were totally removed in 80 cases and subtotally removed in 14
      cases. Postoperative neurological status was improved in 53 cases, unchanged in
      31 cases, and worsened in 10 cases. During follow-up, MRI showed tumor recurrence
      in 4 patients. Histopathologically, three cases were meningiomas and one case was
      neurilemmoma. None of the patients showed spinal instability or kyphotic
      deformity at last follow-up. CONCLUSION: UL is an optimal approach for providing
      sufficient exposure of spinal cord tumors without development of postoperative
      spinal instability and regional sagittal imbalance in any location of spinal
      column. In cases of meningioma, careful long-term follow up is needed due to it's
      relatively high recurrence rate after removal via UL.

PMID- 25983822
TI  - Comparative clinical results of vertebroplasty using jamshidi(r) needle and bone
      void filler for acute vertebral compression fractures.
AB  - OBJECTIVE: Percutaneous vertebroplasty (PVP) is an effective treatment modality
      for management of osteoporotic compression fracture. However physicians sometimes
      have problems of high pressure in cement delivery and cement leakage when using
      Jamshidi(r) needle (JN). Bone void filler (BVF) has larger lumen which may
      possibly diminish these problems. This study aims to compare the radiologic and
      clinical outcome of JN and BVF for PVP. METHODS: One hundred twenty-eight
      patients were treated with PVP for osteoporotic vertebral compression fracture
      (VCF) where 46 patients underwent PVP with JN needle and 82 patients with BVF.
      Radiologic outcome such as kyphotic angle and vertebral body height (VBH) and
      clinical outcome such as visual analog scale (VAS) scores were measured after
      treatment in both groups. RESULTS: In JN PVP group, mean of 3.26 cc of
      polymethylmethacrylate (PMMA) were injected and 4.07 cc in BVF PVP group
      (p<0.001). For radiologic outcome, no significant difference in kyphotic angle
      reduction was observed between two groups. Cement leakage developed in 6 patients
      using JN PVP group and 2 patients using BVF group (p=0.025). No significant
      difference in improvement of VAS score was observed between JN and BVF PVP groups
      (p=0.43). CONCLUSION: For the treatment of osteoporotic VCF, usage of BVF for PVP
      may increase injected volume of cement, easily control the depth and direction of
      PMMA which may reduce cement leakage. However, improvement of VAS score did not
      show difference between two groups. Usage of BVF for PVP may be an alternative to
      JN PVP in selected cases.

PMID- 25983823
TI  - Patterns of epidural venous varicosity in lumbar stenosis.
AB  - OBJECTIVE: Epidural venous varicosity (congestion of the epidural vein) is rarely
      introduced as an influential factor of clinical symptoms. However, there are
      several studies suggesting that epidural venous varicosity results in neurologic
      symptoms. We would like to highlight evidence that epidural venous varicosity
      results in neurologic symptoms and the relation between epidural venous
      varicosity and neural structure observed during the surgery. Based on our
      experiences, we also propose a new classification of epidural venous varicosity.
      METHODS: 29 patients with symptomatic lumbar stenosis received microsurgical
      decompression via partial hemilaminectomy. The authors retrospectively reviewed
      all recorded intraoperative pictures and categorized patterns of venous
      varicosities with relationship to neural structures. RESULTS: Type A is
      conditions in which epidural veins are dilated but located parallel to the nerve
      root on the lateral side of the nerve root and thus do not compress the nerve
      root. Type B is conditions in which varices are located on the anterior lateral
      side of the nerve root to compress the nerve root. Type C is conditions in which
      varices are encircled around the nerve root and compressing the nerve root.
      CONCLUSION: Epidural venous varicosity is observed in most lumbar stenosis
      patients with clinical symptoms. Of the types, the types of epidural venous
      varicosity compressing nerve structures were Type B and Type C. All epidural
      venous varicosities were removed regardless of classification during operations.
      Most patients showed relief in clinical symptoms after the operation. We thought
      to epidural venous varicosity as a factor that causes clinical symptoms of lumbar
      stenosis.

PMID- 25983824
TI  - Intradural extramedullary ependymoma with spinal root attachment: a case report.
AB  - A 36-year-old female patient presented with shoulder pain experienced over a
      period of one year and progressive weakness in both legs for one month. A
      magnetic resonance imaging scan revealed an intradural extramedullary (IDEM)
      fusiform mass about 9.8 cm in length, heterogeneously enhanced at the level of C6
      T4 with spinal cord compression. At the time of surgery, the surgeon found an
      encapsulated IDEM tumor with spinal root attachment. The tumor was completely
      resected and the histologic diagnosis revealed ependymoma. The patient showed a
      favorable outcome with no recurrence at the 6-month follow-up. This paper reports
      a rare case of intradural extramedullary ependymoma with spinal root attachment. 

PMID- 25983825
TI  - Regrowing synovial chondromatosis in a cervical facet joint with radiculopathy.
AB  - Synovial chondromatosis (SC) in the spine is rare. There are few reports of
      associated cervical radiculopathy and there has not been a case reported of
      regrowing cervical SC. Here we report a 21-year-old man with a SC of a cervical
      facet joint that extended into the intervertebral foramen and compressed the
      cervical nerve root. The same symptom developed three years following the first
      operation. Computed tomography (CT) scans and Magnetic resonance imaging (MRI)
      showed multiple calcified nodules anterior to the right facet joint of C6-7 that
      extended into the intervertebral foramen. A mass removal was performed just as in
      the previous operation with a subtotal facetectomy. When vertebral SC is
      suspected, complete removal involving the bone and synovium should be considered
      as the standard treatment option. 

PMID- 25983826
TI  - Spontaneous Resolution of Non-traumatic Cervical Spinal Subdural Hematoma
      Presenting Acute Hemiparesis: A Case Report.
AB  - Spontaneous cervical SDH with no underlying pathology is a very unusual
      condition. To the best of the authors' knowledge, only two cases have been
      previously reported. A 48-year-old female patient was admitted to our emergency
      room due to severe neck pain following standing up position with rapid onset of
      hemiparesis. MRI revealed a dorsolateral subdural hematoma from C3-C5 with cord
      compression. An emergency laminectomy was planned, but motor weakness gradually
      improved during surgical preparation. The patient showed substantial clinical
      improvement and complete recovery was confirmed after 7 days of conservative
      management without surgical treatment. To determine a differential diagnosis
      distinct from other conditions such as cervical epidural hematoma, a lumbar
      spinal puncture was performed. Follow-up MRI performed 10 days after admission
      revealed complete resolution of the hematoma. We report an extremely rare case of
      spontaneous cervical spinal subdural hematoma (SDH), present a review of relevant
      literature, and discuss the etiology, pathogenesis, and prognosis of this case. 

PMID- 25983827
TI  - The complete surgical resection without the radiotherapy for a recurred
      anaplastic ependymoma at the cervicomedullary junction.
AB  - The intramedullary anaplastic ependymoma rarely occurs in the cervicomedullary
      junction. A 45-year-old woman had a history of right arm pain for several months.
      Magnetic resonance imaging (MRI) of the cervical spine demonstrated an
      intramedullary tumor with syrinx at the cervicomedullary junction. The patient
      underwent a partial resection at another institute. Neurologic deficit worsened
      after the first surgery. The follow up MRI showed that the enlarged enhancing
      tumor and syrinx still existed with the same size and configuration. Complete
      surgical resection was achieved in the revision surgery. Final histologic
      examination confirmed the diagnosis of an anaplastic ependymoma, and since
      complete surgical resection was achieved the patient did not receive adjuvant
      radiation or chemotherapy. The patient was followed-up periodically at the
      outpatient department, and at the 7 months follow-up the muscle tone of the right
      hand was normal but with mild sensory deficit, and the MRI demonstrated no
      evidence of recurrent disease. Intramedullary anaplastic ependymoma that occur in
      the cervicomedullary junction which are completely resected may be followed-up
      without adjuvant radiation or chemotherapy to attain good clinical outcome. 

PMID- 25983828
TI  - Primary malignant lymphoma in a spinal cord presenting as an epidural mass with
      myelopathy: a case report.
AB  - We report the case of a 47-year-old man who presented with progressive
      paraparesis and sphincter changes over 2 weeks. Magnetic resonance imaging
      revealed a spinal epidural mass from T9 to L2. We performed a decompressive
      laminectomy and mass removal. The histopathology was consistent with a small
      lymphocytic lymphoma. No metastatic lesion was noted in the chest and abdomen
      pelvic computerized tomography (CT) and positron emission tomography computerized
      tomography (PET-CT) scan. The final diagnosis was primary spinal lymphoma, so we
      performed chemotherapy combined with radiotherapy. At one year follow-up, he had
      no neurological deficit and no recurrence on neurologic and radiologic exams.
      Primary spinal cord lymphomas should be considered in the differential diagnosis
      of spinal cord tumors. Early surgical management is mandatory to achieve a
      recovery of neurologic function, especially if the patient has a neurological
      deficit. 

PMID- 25983829
TI  - Recurrent spinal meningioma: a case report.
AB  - Meningiomas are the second most common intradural spinal tumors accounting for
      25% of all spinal tumors. Being a slow growing and invariably benign tumor, it
      responds favorably to surgical excision. In addition, spinal meningioma has low
      recurrence rates. However, we experienced a case of intradural extramedullary
      spinal meningioma which recurred 16 years after the initial surgery on a 64-year
      old woman. She presented with progressive neurological symptoms and had a
      surgical history of removal of thoracic spinal meningioma 16 years ago due to
      bilateral low leg weakness. She underwent a second operation at the same site and
      a pale yellowish tumor was excised, which was histopathologically confirmed as
      meningothelial meningioma, compared with previously transitional type. she showed
      neurological recovery after the operation. We, therefore, report the good results
      of this recurrent intradural spinal meningioma case developed after 16 years with
      literature review. 

PMID- 25983830
TI  - Primary spinal cord astrocytoma presenting as intracranial hypertension: a case
      report.
AB  - Increased intracranial pressure (IICP) is rarely seen in association with primary
      spinal tumors. We describe a 58-year-old man who was diagnosed with a primary
      spinal cord astrocytoma, who first presented with hypesthesia, followed by
      intracranial hypertension, papilledema and blurred vision. On first admission, he
      presented with hypesthesia but without paraparesis, headache or blurred vision.
      Spinal MRI showed a relatively well-enhanced solid mass with a cystic portion at
      the cervico-thoracic level, shown histologically to be a grade I pilocytic
      astrocytoma. After gross total resection of the tumor, the patient had no
      significant neurological changes. Nine months later, the patient was admitted
      with headache, blurred vision and paraparesis. An ophthalmologic examination
      showed papilledema and lumbar tapping revealed IICP. A spinal MRI showed
      recurrence of the tumor which was found to be a glioblastoma after reexplorative
      debulking surgery. After resection, his headaches and blurred vision improved,
      but his paraparesis did not. These findings show that a primary spinal cord
      astrocytoma may cause IICP. 

PMID- 25983831
TI  - Granular cell tumor of brachial plexus mimicking nerve sheath tumor: a case
      report.
AB  - Primary tumors of the brachial plexus region are rare and granular cell tumors
      arising from the brachial plexus region is an extremely rare disease. We present
      a case of granular cell tumor arising from of the brachial plexus which appeared
      to be a usual presentation of nerve sheath tumor before the pathological
      confirmation. We report a granular cell tumor of the brachial plexus with
      literature review. Total resection is important for good clinical outcome and
      prognosis in the treatment of granular cell tumor. 

PMID- 25983832
TI  - Bilateral locked facets at lower lumbar spine without facet fracture: a case
      report.
AB  - Bilateral locked facets at L4-5 without facet fracture is a rarely known disease.
      We present a case of a 37-year-old male patient diagnosed as traumatic L4-5
      bilateral facets dislocation without facet fracture. We carried out open
      reduction, epidural hematoma removal, posterior interbody fusion. After surgery,
      we attained rapid improvement of the neurologic deficits and competent
      stabilization. 

PMID- 25983833
TI  - Sudden onset of cauda equina syndrome resulting from posterior migration of
      lumbar herniated disc without significant previous neurological signs.
AB  - While extruded disc fragments are known to migrate anteriorly, posteriorly, or
      laterally to the theca sac, posterior migration of the fragments is relatively
      rare and sudden onset of cauda equina syndrome (CES) caused by the migration is
      extremely rare. The authors experienced a case of CES that was manifested
      abruptly with sudden paraplegia caused by posterior migration of the lumbar
      intervertebral disc. A 74-year old man, who had no prior significant neurologic
      signs or trauma history, visited our emergency center with paraplegia of both
      lower extremities occurring suddenly when awakened. On magnetic resonance image
      (MRI) findings, we could detect ruptured disc herniation with severe lumbar
      stenosis at the L2-3 level. We performed an emergent decompression, and the right
      posterior migrated disc fragments at L2-3 were intraoperatively observed. The
      patient was fully recovered himself on the follow up after 3 months of the
      operation. In conclusion, early operation can result in better outcome in acute
      paraplegia caused by the posterior migrated disc fragments. 

PMID- 25983834
TI  - Delayed onset of spinal subdural hematoma after vertebroplasty for compression
      fracture: a case report.
AB  - Vertebroplasty (VP) is a well-known therapeutic modality used to treat pain
      associated with vertebral compression fractures. Major complications such as cord
      or root compression, epidural and subdural hematomas (SDH) and pulmonary emboli,
      occur in less than 1% of patients who undergo VP after compression fracture.
      Spinal SDH is an extremely rare complication that usually happens a few hours
      after the procedure. We report a case of spinal SDH that developed at two weeks
      after a successful VP. We also reviewed related literatures and discussed its
      possible pathogenesis. 

PMID- 25983835
TI  - Delayed pharyngeal extrusion of an anterior odontoid screw.
AB  - A 27-year-old woman with a type II odontoid fracture was treated by anterior
      odontoid screw fixation. Radiographic union at the fracture site was obtained 3
      months after surgery. Nearly 3 years after surgery, she presented at a local Ear,
      Nose, and Throat (ENT) clinic with a 2-month history of dysphagia. Laryngoscopy
      identified the head of the odontoid lag screw. Plain radiography showed that the
      head of the screw had migrated into the pharyngeal soft tissue. The atlantoaxial
      joint was stable, and computed tomography (CT) scans confirmed odontoid fracture
      fusion. The screw was found to be movable during endoscopy. The screw could be
      removed by using a transpharyngeal endoscopic approach under general anesthesia.
      The failure of the screw was considered to be due in part to malpositioning of
      the screw and in part to local infection. A transoropharyngeal endoscopic
      approach to remove the loose anterior odontoid screw was feasible. 

PMID- 25983836
TI  - Intradural extramedullary metastasis of small cell lung cancer: a case report.
AB  - A 60-year-old man presented with para-anesthesia and a tingling sensation in the
      saddle area. Intradural extramedullary (IDEM) tumors in conus medullaris were
      observed by radiologic studies. The patient underwent laminoplastic laminotomy at
      the T12-L2 level and subtotal removal of the tumor because of the ill-defined
      margin. Postoperatively, hypesthesia was improved up to 50%. The IDEM tumor
      revealed a metastatic cancer originated from small cell lung cancer (SCLC) by
      histologic examination, and additional studies showed multiple metastases
      including adrenal gland, brain, and bone. Clinicians need to consider IDEM
      metastasis when SCLC patients were complained of neurologic symptoms mimic
      paraneoplastic syndrome. The pathophysioloigy of IDEM metastasis may be not only
      tertiary drop metastasis, but also faster mechanisms such as direct invasion. 

PMID- 25983837
TI  - Spontaneous cervical epidural hematoma causing brown-sequard syndrome.
AB  - Spontaneous cervical epidural hematoma (SCEH) is a rare clinical entity and has a
      varied etiology. Urgent surgical decompression should be done to prevent serious
      permanent neurologic deficits. We describe a 59-year-old female who presented
      with Brown-Sequard syndrome due to spontaneous cervical epidural hematoma.
      Initially, she was misdiagnosed as cerebrovascular accident. Cervical magnetic
      resonance imaging revealed epidural hematoma to the right of the spinal cord
      extending from C3 to C6. She later underwent surgical evacuation and had complete
      restoration of neurologic function. The outcome in SCEH is essentially determined
      by the time taken from onset of the symptom to operation. Therefore, early and
      precise diagnosis such as careful history taking and MRI evaluation is mandatory.

PMID- 25983838
TI  - Screw loosening and Migration after Dynesys Implantation.
AB  - Due to the problems associated with rigid fixation, the concept of dynamic
      stabilization was introduced. Dynesys is one of the pedicle screw-based dynamic
      stabilization systems. In spite of the dynamic nature of Dynesys, there are
      concerns about the rigidity of the Dynesys system. We present a case of vertebral
      body split fracture after Dynesys implantation in a 74-year-old woman. She had
      undergone L2-L5 laminectomy and Dynesys implantation for spinal stenosis 15
      months ago. She was discharged with improvement in lower back pain and
      claudication. Follow-up X-ray images were taken at 1, 3 and 6 months and there
      was no evidence of screw migration. During the follow-up period, she received
      selective root block due to persistent leg pain. Eight months after the
      operation, she visited our hospital due to severe lower back pain. Magnetic
      resonance imaging showed the features of lumbar spondylitis from L2 to L5. Plain
      X-ray and computed tomography images showed the presence of a superiorly migrated
      screw at L5. The screws migrated superiorly into the intervertebral disc space
      creating a bony defect resembling a sagittal migrated fracture. The Dynesys
      system was removed and lumbar spondylitis was treated with antibiotics. The aim
      of the present case was to demonstrate the problems caused due to rigidity of the
      Dynesys system, when postoperative infection occurs after Dynesys implantation. 

PMID- 25983839
TI  - Unusual fatal infections after anterior cervical spine surgeries.
AB  - We report two cases of cervical spinal epidural abscess (SEA), which are related
      to anterior cervical surgeries. The first case reveals a late postoperative
      infection without any predisposing factor. The second case reveals combined
      complication of infection and instrument failure (artificial disc). Both two
      cases manifested ascending infections that are unusual courses of anterior
      cervical infections. The abscess extended upwards and, finally, caused life
      threatening bacterial meningitis. We suggest aggressive surgical interventions
      with anti-bacterial therapies in such cases. 

PMID- 25983840
TI  - Paraspinal Muscle Sparing Versus Percutaneous Screw Fixation: A Comparative
      Enzyme Study of Tissue Injury during the Treatment of L4-L5 Spondylolisthesis.
AB  - OBJECTIVE: Screw fixation via the paraspinal muscle sparing approach and by
      percutaneous screw fixation are known to diminish the risk of complications, such
      as, iatrogenic muscle injury as compared with the conventional midline approach.
      The purpose of this study was to evaluate tissue injury markers after these less
      traumatic screw fixation techniques for the treatment of L4-L5 spondylolisthesis.
      METHODS: Twenty-two patients scheduled for posterior lumbar interbody fusion
      (PLIF) at the L4-L5 segment for spondylolisthesis were prospectively studied.
      Patients were divided into two groups by screw fixation technique (Group I:
      paraspinal muscle sparing approach and Group II: percutaneous screw fixation).
      Levels of serum enzymes representing muscle injury (CK-MM and Troponin C type 2
      fast), pro-inflammatory cytokine (IL-8), and anti-inflammatory cytokine (IL-1ra)
      were analyzed using ELISA techniques on the day of the surgery and 1, 3, and 7
      days after the surgery. RESULTS: Serum CK-MM, Troponic C type 2 fast (TNNC2), and
      IL-1ra levels were significantly elevated in Group I on postoperative day 1 and
      3, and returned to preoperative levels on postoperative day 7. No significant
      intergroup difference was found between IL-8 levels despite higher concentrations
      in Group I on postoperative day 1 and 3. CONCLUSION: This study shows that
      percutaneous screw fixation procedure is the preferable minimally invasive
      technique in terms of minimizing muscle injury associated with L4-L5
      spondylolisthesis.

PMID- 25983841
TI  - Coccygodynia and coccygectomy.
AB  - OBJECTIVE: A review of the literature on coccygectomy and our patients was
      performed to assess the effectiveness of coccygectomy for chronic refractory
      coccygodynia. METHODS: An English language PubMed search was conducted with the
      terms "coccygodynia" and "coccygectomy" from January 1980 to January 2012. We
      retrospectively reviewed the medical records and performed telephone
      questionnaire on 61 patients who underwent coccygectomy at UCDMC between 1997 and
      2009. RESULTS: There were 28 case series from 1980 to 2012 for a total of 742
      patients who underwent coccygectomy following failed conservative management. The
      mean age ranged from 26.4 to 52.8 years. The most common cause was direct trauma
      (58.5%) with a male:female ratio of 1:5.2. Most patients (84%) had a good to
      excellent outcome after coccygectomy. The most common complication is wound
      infection (10.0%). The overall complication rate was 13.3%. Similarly, 84.6% of
      patients from our own surgical case series reported good to excellent outcomes
      with 11.5% wound infection. CONCLUSION: Coccygectomy is an effective treatment
      for chronic refractory coccygodynia. The surgery isrelatively simple to perform
      but precaution must be taken to avoid wound infection.

PMID- 25983842
TI  - Clinical Effects and Radiological Results of Vertebroplasty: Over a 2-year Follow
      Up Period.
AB  - OBJECTIVE: We investigated the association between clinical and radiological
      results and assessed the radiological changes according to the distribution
      pattern and amount of injected cement after vertebroplasty. METHODS: Two hundred
      and one patients underwent vertebroplasty; of these, 15 were follow up for more
      than 2 years. For radiological analysis, we grouped the patients according to
      cement distribution as follows: group 1, unilateral, unilateral distribution of
      cement; group 2, bilateral-uneven, bilateral distribution of cement but separated
      mass; and group 3, bilateral-even, bilateral single mass of cement. To compare
      radiologic with clinical results, we assessed the visual analogue scale (VAS)
      score, amount of injected cement, bone mineral density (BMD), postoperative and
      follow-up vertebral body compression ratios, and postoperative and follow-up
      kyphotic angles. RESULTS: There were 4 (26.7%) patients in group 1, 6 (40.0%) in
      group 2, and 5 (33.3%) in group 3. The mean VAS score was 5.2 preoperatively, 1.8
      postoperatively, and 3.2 at 2-year follow-up. The 2-year follow-up compression
      ratio was better in patients with even distribution of injected cement (group 2
      and 3) than group 1. However, it was not statistically insignificant (p>0.05).
      The follow-up kyphotic angle was more aggravated in the group 1 than in the other
      groups (p<0.05). CONCLUSION: Our study showed that vertebroplasty had a
      beneficial effect on pain relief, particularly in the immediate postoperative
      stage. The augmented spine tended to be more stable in the cases with increased
      amount and more even distribution of injected cement.

PMID- 25983843
TI  - Primary limited lumbar discectomy with an annulus closure device: one-year
      clinical and radiographic results from a prospective, multi-center study.
AB  - OBJECTIVE: Discectomy as a treatment for herniated lumbar discs results in
      outcomes after surgery that are not uniformly positive. Surgeons face the dilemma
      between limited nucleus removal which is associated with a higher risk of
      recurrence, or more aggressive nucleus removal which may lead to disc height loss
      and persistent back-pain. annulus closure devices may allow for the benefits of
      limited nucleus removal without the increased risk of recurrence. This is an
      interim report of an ongoing 24-month post-marketing study of the Barricaid(r)
      annulus closure device, consisting of a flexible polymer mesh that blocks the
      defect, held in place by a titanium bone anchor. METHODS: We prospectively
      enrolled 45 patients at four hospitals, and implanted the Barricaid(r) after a
      limited discectomy. annulus defect size and volume of removed nucleus were
      recorded. Reherniations were reported, pain and function were monitored and
      imaging was performed at regular intervals during 24 months of follow-up.
      RESULTS: At 12 months postsurgery, pain and function were significantly improved,
      comparing favorably to reported results from limited discectomy. Disc height has
      been well maintained. One reherniation has occurred (2.4%), which was associated
      with a misplaced device. No device fracture, subsidence or migration has been
      observed. CONCLUSION: The use of an annulus closure device may provide a
      reduction in reherniation rate for lumbar discectomy patients with large annulus
      defects who are at the greatest risk of recurrence. Using such a device should
      provide the surgeon increased confidence in minimizing nucleus removal, which, in
      turn, may preserve disc height and biomechanics, reducing degeneration and
      associated poor clinical outcomes in the long-term. A randomized multicenter
      study evaluating limited discectomy with and without the Barricaid(r) is
      currently underway, and will provide a higher level of evidence.

PMID- 25983844
TI  - Symptomatic myelopathy caused by ossification of the yellow ligament.
AB  - OBJECTIVE: This study was performed to describe the clinical presentation,
      surgical outcome in patients with symptomatic myelopathy caused by ossification
      of the yellow ligament (OYL). METHODS: The authors reviewed consequent 12
      patients in whom posterior decompressive laminectomies were performed for OYL
      from 1999 to 2005. Diagnostic imagings including simple radiographs, computed
      tomography and magnetic resonance images were performed in each case. The
      patients were reviewed to evaluate the clinical presentation, surgical outcome
      and complications of the operation. RESULTS: In all patients, OYL was located in
      the lower thoracic region and all patients presented with numbness on both limbs
      and pain. Among them, 5 patients presented with gait disturbance due to
      paraparesis and two patients had sphincter dysfunction. Decompressive laminectomy
      through a posterior approach using microscope resulted in improvement of symptoms
      in all patients, but, recovery was incomplete in a half of the patients. The mean
      postoperative Japanese orthopaedics association (JOA) score was 7.9 when compared
      with 4.9 in preoperative assessment and the mean recovery rate was 65%. Dural
      tear was noticed in four patients, so dural repair was performed, but there were
      no neurological deficits related to neural injury. CONCLUSION: OYL is an uncommon
      cause of myelopathy but it can lead to debilitating thoracic myelopathy. Careful
      decompressive laminectomy can achieve favorable results.

PMID- 25983845
TI  - Minimally invasive multilevel percutaneous pedicle screw fixation for lumbar
      spinal diseases.
AB  - OBJECTIVE: There are rare reports on the result of multilevel (>=3 levels)
      percutaneous pedicle screw fixation (PPF). The purpose of this study was to
      report the clinical experiences for multilevel PPF of the lumbar spine. METHODS:
      A total of 17 patients of lumbar spinal disease (7 degenerative diseases, 6
      infectious diseases, and 4 traumatic instabilities) underwent neural
      decompression and multilevel PPF. There were 8 men and 9 women with a mean age of
      61.4 years (range, 25-84) and a mean follow-up period of 23.2 months (range, 13
      48). The average PPF level was 3.7. A retrospective review of clinical,
      radiological, and surgical data was conducted. RESULTS: "Excellent" or "good"
      clinical results were obtained in 15 patients (88.2%) according to the Odom's
      criteria. The average improvement of visual analogue scale was 5.2 points (from
      9.3 to 4.1), and the average improvement of Oswestry Disability Index was 36.2
      (from 71.2 to 35.0) at the last visit (p<0.05). The fusion rate was 88.2%, but,
      screw loosening was occurred in 2 patients, and adjacent segmental degeneration
      was occurred in 2 patients. There was no statistical significance in the change
      of total lumbar lordotic angle. The average operation time was 5.9 hours, with an
      estimated blood loss of 550 ml and bed rest duration of 2.0 days. CONCLUSION:
      Although the current study examined a small sample with relatively short term
      follow up periods, our study results demonstrate that multilevel PPF is feasible
      and safe for selective lumbar spinal diseases.

PMID- 25983846
TI  - Occipital neuralgia after occipital cervical fusion to treat an unstable
      jefferson fracture.
AB  - In this report we describe a patient with an unstable Jefferson fracture who was
      treated by occipitocervical fusion and later reported sustained postoperative
      occipital neuralgia. A 70-year-old male was admitted to our center with a
      Jefferson fracture induced by a car accident. Preoperative lateral X-ray revealed
      an atlanto-dens interval of 4.8mm and a C1 canal anterior-posterior diameter of
      19.94mm. We performed fusion surgery from the occiput to C5 without decompression
      of C1. The patient reported sustained continuous pain throughout the following
      year despite strong analgesics. The pain dermatome was located mainly in the
      great occipital nerve territory and posterior neck. Magnetic resonance images
      revealed no evidence of cord compression, however a C1 lamina compressed dural
      sac and C2 root compression could not be excluded. We performed bilateral C2 root
      decompression via a C1 laminectomy. After decompression, bilateral C2 root
      redundancy was identified by palpation. After decompression surgery, pain was
      reduced. This case indicates that occipital neuralgia, suggesting the need for
      diagnostic block, should be considered in the differential diagnosis of patients
      with sustained occipital headache after occipitocervical fusion surgery. 

PMID- 25983847
TI  - Hibernoma in the thoracic back muscle accompanied by neurilemmoma.
AB  - Hibernoma is a very rare, benign soft fatty tumor that derived from remnants of
      fetal brown tissue. The following case of hibernoma break out occurred from a
      patient who had received surgical resection of neurilemmoma. There has never been
      a case that reported about hibernoma accompanied by neurilemmoma. It is
      anticipated that this experience would be helpful to other physicians who are
      interested in this rare type of tumor. 

PMID- 25983848
TI  - Symptomatic Epidural Gas-containing Cyst from Intervertebral Vacuum Phenomenon.
AB  - Vacuum disc phenomenon is a collection of gas in the intervertebral disc space
      but rarely causes nerve compression. However, some rare type of vacuum phenomenon
      in the spinal canal may bring about posterior gas displacement within the
      epidural space. The authors describe two patients with symptomatic epidural gas
      containing cyst that seem to be originating from vacuum phenomenon in the
      intervertebral disc, causing lumbosacral radiculopathy. Radiographic studies
      demonstrated intervertebral vacuum phenomenon and accumulation of gas in the
      lumbar epidural space compressing the dural sac and the nerve root. The nerve
      root in both patients was compressed by gas containing cyst that was surrounded
      by thin walled capsule separable from the gaseous degenerated disc space. The
      speculative mechanism of the nerve root compression is discussed. The possibility
      of gas containing cyst should be considered in case of the nerve root compression
      in which epidural gas is present. 

PMID- 25983849
TI  - Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and
      Clusiaceae Plant Species from Mexico.
AB  - The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were
      tested in vitro (50 ug/mL) against Mycobacterium tuberculosis H37Rv and HIV
      reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibited
      M. tuberculosis (>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts
      also inhibited both targets (>58.3% and >67.6%), respectively. The IC50 values
      for six selected extracts and their cytotoxicity (50 ug/mL) to human macrophages
      were then determined. Amphipterygium glaucum, A. molle, and A. simplicifolium
      fairly inhibited M. tuberculosis with IC50 of 1.87-2.35 ug/mL; but their IC50
      against HIV-RT was 59.25-97.83 ug/mL. Calophyllum brasiliense, Vismia baccifera,
      and Vismia mexicana effect on M. tuberculosis was noteworthy (IC50 3.02-3.64
      ug/mL) and also inhibited RT-HIV (IC50 26.24-35.17 ug/mL). These 6 extracts (50
      ug/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles of A.
      glaucum, A. molle, and A. simplicifolium indicated that their antimycobacterial
      activity cannot be related to masticadienonic, 3alpha, or 3beta
      hydromasticadienonic acids, suggesting that other compounds may be responsible
      for the observed activity or this might be a synergy result. The anti-HIV-RT and
      antimycobacterial activities induced by C. brasiliense can be attributed to the
      content of calanolides A, B, as well as soulatrolide. 

PMID- 25983850
TI  - Herb Network Analysis for a Famous TCM Doctor's Prescriptions on Treatment of
      Rheumatoid Arthritis.
AB  - Traditional Chinese Medicine (TCM) doctors always prescribe various herbal
      formulae tailored to individual patients. However, there is still a lack of
      appropriate methods to study the rule and potential biological basis underlying
      the numerous prescriptions. Here we developed an Herb-Compound-Target-Disease
      coherent network approach to analyze 871 herbal prescriptions from a TCM master,
      Mr. Ji-Ren Li, in his clinical practice on treatment of rheumatoid arthritis
      (RA). The core herb networks were extracted from Mr. Li's prescriptions. Then, we
      predicted target profiles of compounds in core herb networks and calculated
      potential synergistic activities among them. We further found that the target
      sets of core herbs overlapped significantly with the RA related biological
      processes and pathways. Moreover, we detected a possible connection between the
      prescribed herbs with different properties such as Cold and Hot and the Western
      drugs with different actions such as immunomodulatory and hormone regulation on
      treatment of RA. In summary, we explored a new application of TCM network
      pharmacology on the analysis of TCM prescriptions and detected the networked core
      herbs, their potential synergistic and biological activities, and possible
      connections with drugs. This work offers a novel way to understand TCM
      prescriptions in clinical practice. 

PMID- 25983851
TI  - A universal matter-wave interferometer with optical ionization gratings in the
      time-domain.
AB  - Matter-wave interferometry with atoms1 and molecules2 has attracted a rapidly
      growing interest throughout the last two decades both in demonstrations of
      fundamental quantum phenomena and in quantum-enhanced precision measurements.
      Such experiments exploit the non-classical superposition of two or more position
      and momentum states which are coherently split and rejoined to interfere3-11.
      Here, we present the experimental realization of a universal near-field
      interferometer built from three short-pulse single-photon ionization
      gratings12,13. We observe quantum interference of fast molecular clusters, with a
      composite de Broglie wavelength as small as 275 fm. Optical ionization gratings
      are largely independent of the specific internal level structure and are
      therefore universally applicable to different kinds of nanoparticles, ranging
      from atoms to clusters, molecules and nanospheres. The interferometer is
      sensitive to fringe shifts as small as a few nanometers and yet robust against
      velocity-dependent phase shifts, since the gratings exist only for nanoseconds
      and form an interferometer in the time-domain.

PMID- 25983852
TI  - A technical support tool for joint range of motion determination in functional
      diagnostics - an inter-rater study.
AB  - BACKGROUND: The examination of joint range of motion (RoM) is part of musculo
      skeletal functional diagnostics, used, for example, in occupational examinations.
      Various examination methodologies exist that have been optimized for occupational
      medical practice, which means they were reduced to the most necessary and
      feasible measures and examinations for efficiency and usability reasons. Because
      of time constraints in medical examinations in occupational settings, visual
      inspection is commonly used to quantify joint RoM. To support medical examiners,
      an inertial sensor-based measurement system (CUELA) was adapted for joint RoM
      examination in these settings. The objective of the present study was to evaluate
      the measurement tool in functional diagnostics under conditions close to clinical
      practice. METHODS: The joint RoM of twenty healthy subjects were examined by
      three physicians, who were simultaneously using the measurement tool. Physicians
      were blinded to the measurement results and the other physicians. Active RoM was
      examined on the cervical, thoracic and lumbar spine while passive RoM was
      examined on the shoulder, elbow, wrist, hip, and knee, resulting in a total of 40
      joint examination angles. The means, standard deviations, intraclass correlation
      coefficients (I C C 3,k ), and Bland-Altman-Plots were calculated using MatLab
      for statistical analysis. RESULTS: Most measurement results were in accordance
      with expected joint RoMs. All examinations showed an acceptable repeatability. In
      active RoM examinations, the ICC of inter-rater reliability varied between 0.79
      and 0.95. In passive RoM examination the ICC varied between 0.71 and 0.96, except
      examination angles at the elbow and knee extension (ICC: 0.0-0.77). CONCLUSION:
      The reliability and objectivity of active RoM examinations were improved by the
      measurement tool compared with examiners. In passive RoM examinations of upper
      and lower extremities, the increase of objectivity by the measurements was
      limited for some examination angles by external factors such as the individual
      examiner impact on motion execution or the given joint examination conditions.
      Especially the elbow joint examination requires further development to achieve
      acceptable reliability. A modification in the examination method to reduce the
      examiner impact on measurement and the implementation of a more complex
      calibration procedure could improve the objectivity and reliability of the
      measurement tool in passive joint RoM examination to be applicable on nearly the
      whole body.

PMID- 25983853
TI  - Transition of youth living with HIV from pediatric to adult-oriented healthcare:
      a review of the literature.
AB  - Due to advances in antiretroviral therapy, most HIV-infected children and youth
      now survive into adulthood. Many experts and professional societies have
      expressed concern about potential disruptions to care when youth living with HIV
      transition from pediatric to adult-oriented medical care. However, original
      research focused on this transition process is rare. The existing literature can
      be organized into the following categories: pre-transition assessments of
      anticipated barriers and concerns; studies describing provider practices during
      the transition period; and post-transition retrospective analyses after
      transition to adult care. Most studies had small sample sizes and focused on
      vertically infected youth. Further work is needed to document clinical outcomes
      after transition and to evaluate transition protocols that are in place at some
      institutions.

PMID- 25983646
TI  - Measurement of the production and lepton charge asymmetry of [Formula: see text]
      bosons in Pb+Pb collisions at [Formula: see text] with the ATLAS detector.
AB  - A measurement of [Formula: see text] boson production in lead-lead collisions at
      [Formula: see text] is presented. It is based on the analysis of data collected
      with the ATLAS detector at the LHC in 2011 corresponding to an integrated
      luminosity of 0.14 [Formula: see text] and 0.15 [Formula: see text] in the muon
      and electron decay channels, respectively. The differential production yields and
      lepton charge asymmetry are each measured as a function of the average number of
      participating nucleons [Formula: see text] and absolute pseudorapidity of the
      charged lepton. The results are compared to predictions based on next-to-leading
      order QCD calculations. These measurements are, in principle, sensitive to
      possible nuclear modifications to the parton distribution functions and also
      provide information on scaling of [Formula: see text] boson production in multi
      nucleon systems.

PMID- 25983854
TI  - Hepatitis C Virus. Strategies to Evade Antiviral Responses.
AB  - Hepatitis C virus (HCV) causes chronic liver disease and poses a major clinical
      and economic burden worldwide. HCV is an RNA virus that is sensed as non-self in
      the infected liver by host pattern recognition receptors, triggering downstream
      signaling to interferons (IFNs). The type III IFNs play an important role in
      immunity to HCV, and human genetic variation in their gene loci is associated
      with differential HCV infection outcomes. HCV evades host antiviral innate immune
      responses to mediate a persistent infection in the liver. This review focuses on
      anti-HCV innate immune sensing, innate signaling and effectors, and the processes
      and proteins used by HCV to evade and regulate host innate immunity.

PMID- 25983857
TI  - Effects of field plot size on prediction accuracy of aboveground biomass in
      airborne laser scanning-assisted inventories in tropical rain forests of
      Tanzania.
AB  - BACKGROUND: Airborne laser scanning (ALS) has recently emerged as a promising
      tool to acquire auxiliary information for improving aboveground biomass (AGB)
      estimation in sample-based forest inventories. Under design-based and model
      assisted inferential frameworks, the estimation relies on a model that relates
      the auxiliary ALS metrics to AGB estimated on ground plots. The size of the field
      plots has been identified as one source of model uncertainty because of the so
      called boundary effects which increases with decreasing plot size. Recent
      research in tropical forests has aimed to quantify the boundary effects on model
      prediction accuracy, but evidence of the consequences for the final AGB estimates
      is lacking. In this study we analyzed the effect of field plot size on model
      prediction accuracy and its implication when used in a model-assisted inferential
      framework. RESULTS: The results showed that the prediction accuracy of the model
      improved as the plot size increased. The adjusted R2 increased from 0.35 to 0.74
      while the relative root mean square error decreased from 63.6 to 29.2%.
      Indicators of boundary effects were identified and confirmed to have significant
      effects on the model residuals. Variance estimates of model-assisted mean AGB
      relative to corresponding variance estimates of pure field-based AGB, decreased
      with increasing plot size in the range from 200 to 3000 m2. The variance ratio of
      field-based estimates relative to model-assisted variance ranged from 1.7 to 7.7.
      CONCLUSIONS: This study showed that the relative improvement in precision of AGB
      estimation when increasing field-plot size, was greater for an ALS-assisted
      inventory compared to that of a pure field-based inventory.

PMID- 25983858
TI  - Avoiding treatment bias of REDD+ monitoring by sampling with partial replacement.
AB  - BACKGROUND: Implementing REDD+ renders the development of a measurement,
      reporting and verification (MRV) system necessary to monitor carbon stock
      changes. MRV systems generally apply a combination of remote sensing techniques
      and in-situ field assessments. In-situ assessments can be based on 1) permanent
      plots, which are assessed on all successive occasions, 2) temporary plots, which
      are assessed only once, and 3) a combination of both. The current study focuses
      on in-situ assessments and addresses the effect of treatment bias, which is
      introduced by managing permanent sampling plots differently than the surrounding
      forests. Temporary plots are not subject to treatment bias, but are associated
      with large sampling errors and low cost-efficiency. Sampling with partial
      replacement (SPR) utilizes both permanent and temporary plots. RESULTS: We apply
      a scenario analysis with different intensities of deforestation and forest
      degradation to show that SPR combines cost-efficiency with the handling of
      treatment bias. Without treatment bias permanent plots generally provide lower
      sampling errors for change estimates than SPR and temporary plots, but do not
      provide reliable estimates, if treatment bias occurs, SPR allows for change
      estimates that are comparable to those provided by permanent plots, offers the
      flexibility to adjust sample sizes in the course of time, and allows to compare
      data on permanent versus temporary plots for detecting treatment bias.
      Equivalence of biomass or carbon stock estimates between permanent and temporary
      plots serves as an indication for the absence of treatment bias while differences
      suggest that there is evidence for treatment bias. CONCLUSIONS: SPR is a flexible
      tool for estimating emission factors from successive measurements. It does not
      entirely depend on sample plots that are installed at the first occasion but
      allows for the adjustment of sample sizes and placement of new plots at any
      occasion. This ensures that in-situ samples provide representative estimates over
      time. SPR offers the possibility to increase sampling intensity in areas with
      high degradation intensities or to establish new plots in areas where permanent
      plots are lost due to deforestation. SPR is also an ideal approach to mitigate
      concerns about treatment bias.

PMID- 25983856
TI  - The Current State of Vaccine Development for Ocular HSV-1 Infection.
AB  - HSV-1 continues to be the leading cause of infectious corneal blindness. Clinical
      trials for vaccines against genital HSV infection have been ongoing for more than
      three decades. Despite this, no approved vaccine exists, and no formal clinical
      trials have evaluated the impact of HSV vaccines on eye health. We review here
      the current state of development for an efficacious HSV-1 vaccine and call for
      involvement of ophthalmologists and vision researchers.

PMID- 25983855
TI  - Developing novel anti-fibrotic therapeutics to modulate post-surgical wound
      healing in glaucoma: big potential for small molecules.
AB  - Ocular fibrosis leads to significant visual impairment and blindness in millions
      of people worldwide, and is one of the largest areas of unmet need in clinical
      ophthalmology. The antimetabolites, mitomycin C and 5-fluorouracil, are the
      current gold standards used primarily to prevent fibrosis after glaucoma surgery,
      but have potentially blinding complications like tissue damage, breakdown and
      infection. This review thus focuses on the development of new classes of small
      molecule therapeutics to prevent post-surgical fibrosis in the eye, especially in
      the context of glaucoma filtration surgery. We discuss recent advances and
      innovations in ophthalmic wound healing research, including antibodies, RNAi,
      gene therapy, nanoparticles, liposomes, dendrimers, proteoglycans and small
      molecule inhibitors. We also review the challenges involved in terms of drug
      delivery, duration of action and potential toxicity of new anti-fibrotic agents
      in the eye.

PMID- 25983862
TI  - Spinal cord compression from a brown tumour despite maximal medical therapy with
      cinacalcet and sevelamer.

PMID- 25983863
TI  - Thrombotic microangiopathy associated with sunitinib, a VEGF inhibitor, in a
      patient with factor V Leiden mutation.

PMID- 25983864
TI  - Rhabdomyolysis after ezetimibe/simvastatin therapy in an HIV-infected patient.

PMID- 25983859
TI  - Development of Risky Decision Making: Fuzzy-Trace Theory and Neurobiological
      Perspectives.
AB  - Developmental differences in mental representations of choices, reward
      sensitivity, and behavioral inhibition (self-control) explain greater
      susceptibility to risk taking. Ironically, relying on precise representations in
      reasoning promotes greater risk taking, but this reliance declines as adolescents
      mature. This phenomenon is known as a developmental reversal; it is called a
      reversal because it violates traditional developmental expectations of greater
      cognitive complexity with maturation. Fuzzy-trace theory (FTT) predicts reversals
      by proposing two types of mental representation (gist and verbatim), and that
      risk takers rely more on verbatim processing when making decisions. In this
      article, we describe the main tenets of FTT and explain how it can account for
      risky decision making. We also explore the neural underpinnings of development
      and decision making in the context of distinctions from FTT. FTT's predictions
      elucidate unanswered questions about risk taking, providing directions for
      research.

PMID- 25983861
TI  - Successful use of low-dose intravenous paricalcitol in the treatment of severe
      secondary hyperparathyroidism in a haemodialysis patient.

PMID- 25983865
TI  - New onset of alopecia in a young woman with end-stage renal disease.

PMID- 25983867
TI  - A patient with Henoch-Schonlein purpura and intra-alveolar haemorrhage.

PMID- 25983866
TI  - Alloimmune haemolysis in a renal transplant recipient receiving sirolimus.

PMID- 25983868
TI  - End-stage renal failure associated with congenital deafness.

PMID- 25983860
TI  - Adynamic bone disease-bone and beyond.

PMID- 25983869
TI  - Nephrotic syndrome and chronic kidney disease in a young African patient from
      Saint Thomas and Prince: what is the link?

PMID- 25983870
TI  - Viral haemorrhagic fever and a skin rash-what is the link?

PMID- 25983871
TI  - Fibrillary comma-shaped electron-dense organized glomerular deposits associated
      with cryoglobulinaemia.

PMID- 25983872
TI  - End-stage renal disease with giant bladder calculus.

PMID- 25983873
TI  - Digital necrosis after low-dose dopamine treatment.

PMID- 25983874
TI  - Intramembranous electron-dense deposits in a nephrotic patient with mixed
      connective tissue disease: unusual response to corticosteroid therapy.

PMID- 25983875
TI  - Intrarenal reflux.

PMID- 25983876
TI  - Encapsulating peritoneal sclerosis-a life-threatening condition treated
      successfully with adhesiolysis and Jones tube insertion.

PMID- 25983877
TI  - Investigation of the association between oral sodium phosphate use and kidney
      injury.

PMID- 25983878
TI  - The implications of aspirin resistance in renal failure.

PMID- 25983879
TI  - Gadolinium-based contrast agents, erythropoietin and nephrogenic systemic
      fibrosis in patients with end-stage renal failure.

PMID- 25983880
TI  - Cystatin C as a surrogate for glomerular filtration rate in the presence of
      proteinuria.

PMID- 25983881
TI  - Impact of cetuximab conventional dosing on cetuximab-induced magnesium
      concentration under haemodialysis in head and neck cancer.

PMID- 25983882
TI  - Correction of metabolic acidosis after conversion from sevelamer hydrochloride to
      lanthanum carbonate.

PMID- 25983883
TI  - Left ventricular dysfunction in the haemodialysis population.
AB  - Cardiovascular disease in the haemodialysis population continues to contribute to
      mortality and morbidity. Disorders of left ventricular geometry and function are
      highly prevalent and lead to increased mortality in this highly vulnerable
      population. Left ventricular dysfunction (LVDys), often as a result of
      hypertension, ischaemic cardiac disease or dilated cardiomyopathy, has not been
      uniformly defined in the literature making diagnosis and therapy problematic.
      Although routinely available, screening by echocardiography is critically volume
      dependent and prone to underestimation in left ventricular ejection fraction. Few
      randomized control trials are available to guide management with the majority of
      evidence requiring extrapolation from the non-dialysis population. Beyond
      medication, interventional cardiac procedures such as implantable cardiac
      defibrillator implantation and cardiac resynchronization therapy show promise.
      Conversion to alternative dialysis modalities such as peritoneal dialysis, short
      daily or nocturnal dialysis have been attempted and are actively being explored. 

PMID- 25983885
TI  - Reversible Fanconi syndrome due to lenalidomide.

PMID- 25983884
TI  - Metabolic syndrome in peritoneal dialysis patients.
AB  - Cardiovascular morbidity and mortality are common in peritoneal dialysis
      patients. Metabolic syndrome (MES) is a medical condition with a clustering of
      major risk factors for cardiovascular diseases. In this review article, the
      various diagnostic criteria used in MES are discussed. It is proposed to use a
      modified National Cholesterol Education Programme Adult Treatment Panel III (NCEP
      ATP III) criteria for the diagnosis of MES in peritoneal dialysis (PD) patients
      taking into consideration the scientific evidence and practicality. When three or
      more of the following criteria are satisfied in PD patients, obesity, high
      triglyceride, low high-density lipoprotein cholesterol (HDL-C), hypertension or
      dysglycaemia, they are diagnosed as having MES. Body mass index (BMI) with
      reference to ethnicity is suggested to replace waist circumference for diagnosing
      obesity. Epidemiology and outcome of PD patients with MES are highlighted. The
      adverse sequelae of obesity appear to be primarily due to fat mass rather than
      non-fat mass, possibly related to the pro-inflammatory effect of adipose tissue.
      Whilst there are therapies to tackle MES in PD patients, more conclusive data in
      human studies to see clinically improved outcomes with such strategies are
      needed. 

PMID- 25983886
TI  - Clinical and histological features of lupus nephritis induced by anti-TNFalpha
      therapy.
AB  - It is known that anti-TNFalpha therapy has opened a new era in treatment of
      rheumatoid arthritis, and it is emerging as a new successful treatment in the
      current rheumatologic practice. Besides, there is evidence that this therapy is
      an important cause of iatrogenic autoimmune disease. Several studies reported the
      possible onset of lupus syndrome that can be resolved with withdrawal of anti
      TNFalpha drugs. Our report describes the first lupus nephritis case developing in
      a rapidly progressive renal failure that required haemodialysis treatment in a
      patient affected with rheumatoid arthritis, treated with anti-TNFalpha therapy.
      So, we confirm the importance of a careful clinic and immunologic evaluation
      before starting anti-TNFalpha therapy. 

PMID- 25983887
TI  - Fibronectin glomerulopathy: an uncommon cause of nephrotic syndrome in systemic
      lupus erythematosus.

PMID- 25983888
TI  - Acute renal failure caused by prolonged djembe drumming.

PMID- 25983889
TI  - Antibody-mediated pure red cell aplasia (PRCA) on switching from darbepoetin alfa
      to epoetin beta: what are the implications?
AB  - We report the development of antibody-mediated pure red cell aplasia (PRCA) in a
      63-year-old man with end-stage renal disease following a switch from darbepoetin
      alfa to epoetin beta. Haemoglobin levels began to decrease 6 months after the
      switch. Increasing the epoetin beta dose produced no response and regular blood
      transfusions were required; PRCA was confirmed and epoetin beta was discontinued.
      The patient responded positively to immunosuppression; after 2 months on
      prednisone and cyclophosphamide, haemoglobin levels stabilized and no further
      transfusions were required. This case highlights the difficulty in establishing a
      cause-effect relationship where more than one erythropoiesis-stimulating agent is
      involved. 

PMID- 25983891
TI  - An unusual pulmonary complication of cytomegalovirus infection in a renal
      transplant recipient.

PMID- 25983890
TI  - Pegylated interferon alpha-2a monotherapy in a peritoneal dialysis patient with
      chronic hepatitis C.
AB  - BACKGROUND: Although pegylated interferon (PEG-IFN) is now the standard treatment
      for chronic hepatitis C, there are few reports targeting dialysis patients and
      treatment protocol for hepatitis C virus (HCV) infection has not been determined,
      particularly in patients on peritoneal dialysis. CASE: A 34-year-old woman with
      chronic hepatitis C started peritoneal dialysis because of progressive renal
      disease 2 years after peripheral blood stem cell transplantation for aplastic
      anaemia. The regimen was a single 6-h dwell of 2L glucose dialysate. Considering
      that her HCV genotype was 2a and that she was a candidate for cadaveric kidney
      transplant, we decided to treat her with PEG-IFN alpha-2a monotherapy 1 year
      after the beginning of peritoneal dialysis. We adopted a dose escalation strategy
      to minimize the total amount of PEG-IFN administration, thereby reducing the risk
      of adverse effects. Her HCV-RNA disappeared at the 17th week and sustained virus
      response was achieved thereafter. Only minor side effects were observed including
      flu-like symptoms and mild anaemia, and residual renal function remained stable
      during the treatment of 48 weeks (renal Kt/V; from 1.28 to 1.26). CONCLUSION: PEG
      IFN monotherapy with dose modification may be a safe and effective treatment for
      HCV infection in patients undergoing peritoneal dialysis.

PMID- 25983892
TI  - Urogenital mycoplasma: an emerging cause of deep wound infection after kidney
      transplantation?

PMID- 25983893
TI  - Seronegative hepatitis C-related fibrosing cholestatic hepatitis after renal
      transplant: a case report and review of the literature.

PMID- 25983894
TI  - Hyperbaric oxygen as effective adjuvant therapy in the treatmentof distal
      calcific uraemic arteriolopathy.

PMID- 25983895
TI  - A dialysis patient with blurred vision.

PMID- 25983896
TI  - Infective endocarditis in haemodialysis patients: 16-year experience at one
      institution.
AB  - Objectives. To ascertain the characteristics, outcomes and correlates of
      mortality in chronic haemodialysis patients with confirmed infective endocarditis
      (IE). Methods. Patients were identified by computerized discharge diagnosis and
      chart review of admissions to Saint Louis University hospital from January 1990
      through January 2006. Modified Duke Criteria were retrospectively applied to
      confirm the diagnosis of IE. Survivors and non-survivors were compared to
      identify clinical correlates of IE mortality. Results. We identified 59 patients
      with IE who had received dialysis for a mean duration of 52.9 +/- 58.0 months
      prior to IE diagnosis. Dialysis access comprised 28 (47.5%) catheters, 26 (44.1%)
      arteriovenous grafts, 3 (5.1%) arteriovenous fistulas and 2 (3.4%) life sites.
      The causative organisms were MRSA in 15 (25%), MSSA 12 (20%), S. Epidermidis 10
      (17%), Enterococci 8 (14%), multi-organism 6 (10%), gram negative 2 (3%) and VRE
      1 (2%). Valves involved were mitral valve in 37 (63%), aortic valve in 10 (17%),
      tricuspid valve in 3 (5%) and multiple valves in 8 (13%) cases. Patient mortality
      was 28.8% (n = 17) during hospitalization, 37.9% (n = 22) at 30 days and 63.1% (n
      = 36) at 1 year. In multivariable logistic regression, the adjusted odds ratio of
      in-hospital mortality was 3.6-fold higher in those with IE and arteriovenous
      grafts (P = 0.04, 95% CI 1.04-12.27) compared to other forms of dialysis access.
      Conclusion. Mortality of IE remains high, despite the availability of potent
      antibiotics. Patients with arteriovenous grafts who develop IE may face increased
      risk for in-hospital mortality, perhaps reflecting difficulty eradicating
      endovascular infection if a graft is involved. 

PMID- 25983897
TI  - Slow progression of chronic renal failure in a woman of short stature and leg
      deformities: what is the link?

PMID- 25983898
TI  - A rare complication of Tenckhoff catheter insertion.

PMID- 25983900
TI  - Multiple thyroid cysts as an extra-renal manifestation of ADPKD.

PMID- 25983899
TI  - Emphysematous pyelonephritis leading to end-stage renal failure.

PMID- 25983901
TI  - Heterotopic calcification.

PMID- 25983902
TI  - Ibuprofen codeine combination precipitating severe hypokalaemia in a patient with
      pre-existing type 1 renal tubular acidosis.

PMID- 25983903
TI  - Are segments of the developing world competing in end-stage renal disease (ESRD)?

PMID- 25983904
TI  - Proximal tubular dysfunction associated with tenofovir in an HVC-HIV co-infected
      patient undergoing HVC therapy.

PMID- 25983905
TI  - A new case of Finnish-type congenital nephrotic syndrome, neuromuscular symptoms
      and early death.

PMID- 25983906
TI  - Viruses may trigger allopurinol hypersensitivity syndrome.

PMID- 25983907
TI  - A case of lethal enteroviral haemolytic uraemic syndrome?

PMID- 25983908
TI  - A proposal of the simple guide regarding the conversion ratio from epoetin to
      darbepoetin alpha in treating haemodialysis patients with renal anaemia.

PMID- 25983909
TI  - Streptococcus vestibularis bacteremia following dental extraction in a patient on
      long-term hemodialysis: a case report.

PMID- 25983910
TI  - Interaction between estradiol and tacrolimus in kidney-transplanted menopausal
      women.

PMID- 25983911
TI  - Argatroban caused severe hypercholesterolaemia in a chronic haemodialysis patient
      with heparin-induced thrombocytopenia: an unreported adverse effect?

PMID- 25983912
TI  - Effect of online haemodialysis vascular access flow evaluation and pre-emptive
      intervention on the frequency of access thrombosis.
AB  - Introduction. Guidelines advocate surveillance of vascular access to reduce
      incidences of thrombosis. However, the value of online vascular access flow
      monitoring is still under debate. Methods. Through a systematic literature
      search, the effect of online access flow surveillance combined with pre-emptive
      intervention on thrombosis frequency is reviewed. Results. Due to methodological
      differences, adequate comparison of the individual study results is not possible.
      Moreover, the methodological quality of most of the included studies is not
      suitable for an adequate statistical analysis of the results. Conclusion. Until
      now, there is no conclusive evidence that online access flow evaluation has a
      significant effect on the rate of thrombosis. Future large-scale studies with
      adequate study design, adequate surveillance and intervention protocols and,
      possibly, better pre-emptive intervention alternative(s) are necessary. 

PMID- 25983913
TI  - Life at the UK renal registry-an unforgettable experience.

PMID- 25983914
TI  - Bilineal inheritance of type 1 autosomal dominant polycystic kidney disease
      (ADPKD) and recurrent fetal loss.
AB  - We report for the first time a family with type 1 ADPKD in which the marriage
      between affected non-consanguinous individuals resulted in two live-born
      heterozygous offspring and two fetuses lost in mid-pregnancy. Given a 25% chance
      for mutant compound heterozygosity in the offspring of this family, our findings
      suggest that compound heterozygosity of PKD1 mutations in humans may be
      embryonically lethal. 

PMID- 25983915
TI  - Is adenine phophorybosiltransferase deficiency a still underdiagnosed cause of
      urolithiasis and chronic renal failure? A report of two cases in a family with an
      uncommon novel mutation.
AB  - We describe two patients that had a history of recurrent renal stones and chronic
      renal insufficiency. The first case was a 51-year-old man with an adenine
      phophoribosyltransferase (APRT) deficiency who was diagnosed only after he had
      been referred for severe renal failure requiring hemodialysis. This led to a
      screening of the entire family, which identified six carriers and an additional
      affected relative (a 41-year-old man and the second case reported herein).
      Genetic analysis of the APRT gene revealed an atypical mutation previously
      described only once in a compound heterozygote. 

PMID- 25983916
TI  - Two cases of iodixanol-induced pancreatitis.

PMID- 25983917
TI  - Abrupt and durable remission of Henoch-Schonlein purpura nephritis with
      cyclosporine A.
AB  - Henoch-Schonlein purpura glomerulonephritis (HSP-GN) is a common form of systemic
      small vessel vasculitis in children. Although prognosis is usually favourable,
      the disease is occasionally associated with a risk of renal insufficiency.
      Various immunosuppressive agents have been used in patients with severe HSP-GN,
      but none have shown convincing favourable effects. We report a case of biopsy
      proven HSP-related GN in a 4-year-old girl that responded remarkably well to
      cyclosporine A (CsA), following failure to respond to other immunosuppressive
      agents. At 8 months post-CsA treatment, repeat renal biopsy findings were
      consistent with histological improvement. We conclude that CsA treatment not only
      exerts beneficial effects on resistant HSP-related GN but may also arrest
      progression of the disease. 

PMID- 25983918
TI  - Successful treatment of Henoch-Schonlein purpura nephritis with plasma exchange
      in an adult male.
AB  - Henoch-Schonlein purpura (HSP) frequently occurs in children under 15 years of
      age but is quite rare in adults. Most children who develop HSP nephritis
      completely recover from the illness, whereas up to 40% of adults have persistent
      hematuria and 10% develop chronic renal failure. Plasma exchange alone has been
      shown to be beneficial in children who have HSP nephritis. Adults have been
      treated using immunosuppressive drugs such as cyclophosphamide but effects are
      not certain. Here, we present a case of a 59-year-old white male who developed
      HSP nephritis while undergoing treatment with steroids. The patient developed
      acute renal failure with proteinuria and hematuria ~2 weeks after being initially
      diagnosed with HSP by skin biopsy. Renal biopsy showed proliferative, exudative
      glomerulonephritis involving all 20 glomeruli; some with early crescent
      formation. Immunofluorescence staining showed 3+ IgA deposits in mesangium
      suggesting HSP-induced GN. The patient's serum creatinine rose to 2.5 mg/dl with
      ~5 g of proteinuria by dipstick. Steroids were continued and the patient received
      plasma exchange treatments. Due to a very low leukocyte count, immunosuppressive
      agents were not given. Subsequently, renal function improved and the creatinine
      level came down to 1.3 mg/dl and proteinuria to <1 g/24 h. Since then, 1 year
      after this event, his serum creatinine has continued to stay at 1.2 mg/dl and he
      has trace proteinuria while taking a low-dose ACE inhibitor. This case
      illustrates the usefulness of plasma exchange in adult onset HSP nephritis, even
      without concomitant use of cytotoxic agents. 

PMID- 25983920
TI  - Obstructive nephropathy and kidney injury associated with ketamine abuse.

PMID- 25983921
TI  - Rapamycin-induced remission of Kaposi's sarcoma is not associated with expansion
      of cytotoxic T-lymphocyte subsets.
AB  - We present a case of post-transplantation Kaposi's sarcoma (KS) successfully
      treated by conversion to rapamycin. Clinical and histological resolution was
      observed within 6 months of commencing rapamycin. Also, vascular endothelial
      growth factor (VEGF) staining in the biopsy samples resolved following rapamycin
      therapy. Interestingly there was no expansion in cytotoxic T-lymphocyte (CTL)
      subsets observed during this period, as might be expected if this remission was
      due to immune reconstitution following reduction in immunosuppression. These data
      suggest that the resolution of tumour with rapamycin could be the result of the
      antiangiogenic, antiproliferative effects of rapamycin. 

PMID- 25983922
TI  - Renal failure and abdominal pain as the presenting symptoms of a rare tumor of
      the aorta masquerading as a calcified plaque.
AB  - Vascular obstructive causes must be considered in chronic renal failure with no
      obvious cause. We present the case of a 74-year-old woman with smoldering renal
      failure who undergoes a renal biopsy that did not undercover a cause. As her
      symptoms persisted and renal function worsened, her nephrologist proposed
      magnetic resonance angiography with gadolinium and prophylactic initiation of
      hemodialysis. Imaging uncovered an occlusive aortic mass, which was removed
      surgically with improvement in renal function. The case discusses the nature of
      the mass and the need to weigh the risks and benefits of MR imaging with
      gadolinium and initiation of hemodialysis against the risk of nephrogenic
      systemic fibrosis. 

PMID- 25983919
TI  - Massive uric acid nephrolithiasis with progressive renal failure due to
      spontaneous tumour lysis syndrome.
AB  - Tumour lysis syndrome (TLS) is a constellation of meta- bolic complications due
      to the rapid destruction of malignant cells, causing renal, cardiac or cerebral
      dysfunction. Electrolyte abnormalities include hyperuricaemia,
      hyperphosphataemia, hyperkalaemia and hypocalcaemia. TLS-induced renal failure is
      mainly caused by uric acid and calcium phosphate crystal deposition and usually
      develops following cytotoxic chemotherapy. Here, we present a case of spontaneous
      TLS in a patient with chronic myelomonocytic leukaemia (CMML) with massive uric
      acid stone and crystal formation and rapidly worsening renal failure. Autopsy
      revealed underlying tumourous kidney infiltration. Risk factors for occurrence of
      TLS and current therapeutic management are discussed. 

PMID- 25983923
TI  - Membranoproliferative glomerulonephritis associated with an Epstein-Barr virus
      infection.
AB  - Type 1 membranoproliferative glomerulonephritis (MPGN) is an immune complex
      mediated disorder that has been associated with certain viral infections
      including hepatitis C, hepatitis B, hepatitis G, HIV and Hantavirus. We describe
      a patient with type 1 MPGN in native kidneys and nephrotic syndrome in whom there
      was strong evidence that a primary Epstein-Barr virus (EBV) infection played a
      causative role. This patient was treated with an angiotensin 2-receptor blocker
      and the nephrotic syndrome resolved within 6 months from presentation. Our case
      report suggests that MPGN presenting with nephrotic syndrome may have a
      relatively benign course when it is associated with an acute EBV infection. 

PMID- 25983924
TI  - Permanent renal failure induced by pentastarch.
AB  - Background. Controversy exists with volume resuscitation using crystalloids or
      colloids. Renal dysfunction has been reported with some colloids and osmotic
      agents, but remains poorly defined. Patient. We report the case of a 67-year-old
      male who had normal kidney function at baseline and who developed anuric ARF in
      relation to the administration of >10 litres of 10% pentastarch. A renal biopsy
      confirmed hydropic changes in tubular cells compatible with colloid-induced
      damage. Conclusion. This case demonstrates that hydroxyethyl starch preparations
      may be associated with acute kidney injury, and one should carefully consider
      their use, especially in patients with pre-existing renal dysfunction. Osmotic
      tubular cell lesions may be long lasting and irreversible. 

PMID- 25983925
TI  - Salvage of a radiocephalic fistula by the palmar arch.
AB  - We present a child with mild problems during haemodialysis due to stenosis of the
      proximal radial artery of his radiocephalic fistula. However, his problems
      spontaneously subsided. Follow-up sonography revealed arterial occlusion proximal
      to the fistula with retrograde flow in the distal segment. Kt/V and shunt flow
      were normal. Physical examination confirmed proximal radial artery occlusion with
      collateral blood supply via the palmar arch. There were no signs of steal. To our
      knowledge this is the first description of a patient experiencing adequate
      haemodialysis with arterial occlusion proximal to a radiocephalic fistula
      salvaged by collateral arterial supply via the palmar arch. 

PMID- 25983926
TI  - Sustained low-efficiency dialysis (SLED) for acute lithium intoxication.
AB  - Acute lithium intoxication may cause serious neurologic and cardiac
      manifestations, up to the patient's death. Owing to its low molecular weight,
      relatively small volume of distribution close to that of total body water, and
      its negligible protein binding, lithium can be efficiently removed by any
      extracorporeal modality of renal replacement therapy (RRT). However, the shift
      from the intracellular to the extracellular compartment, with the inherent
      rebound phenomenon after the end of RRT, might limit the efficacy of the
      conventional, short-lasting haemodialysis. There have been no published studies
      up to now concerning the use of sustained low-efficiency dialysis (SLED) in
      lithium intoxication. This report describes a woman with a voluntary acute
      lithium ingestion of 40 tablets of lithium carbonate (8.12 mEq lithium each). The
      lithium concentration increased up to 4.18 mEq/l about 24 h after admission,
      notwithstanding treatment with intravenous crystalloids and gastric lavage. She
      developed mental status changes, oliguria, hypotension and bradycardia. We
      started SLED (8 h) with a blood flow of 200 ml/min and countercurrent dialysate
      flow of 300 ml/min. Lithium serum levels decreased by 86% during treatment, and
      the patient fully awoke recovering a normal mental status within the first 4 h of
      treatment. SLED was completed safely within the prescribed time. After the end of
      treatment, the rebound of lithium concentration was unremarkable. Renal function
      fully recovered, and the patient was transferred into a psychiatric facility 3
      days after admission. 

PMID- 25983927
TI  - Encapsulating peritoneal sclerosis following renal transplantation despite
      tamoxifen and immunosuppressive therapy.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare disease in patients who have
      undergone peritoneal dialysis (PD). We report a case of EPS following renal
      transplantation that highlights important clinical issues. Initially, a
      presumptive diagnosis of EPS was made following surgical and pathological
      findings at the time of cholecystectomy. CT imaging at this time did not confirm
      the diagnosis. The patient continued PD and commenced tamoxifen. Prior to and
      immediately following transplantation, further CT imaging demonstrated no
      evidence of EPS. Acute bowel obstruction occurred 5 months post-transplantation
      and a diagnosis of EPS was made both clinically and on CT imaging, despite
      immunosuppression and tamoxifen. The role of these therapies in managing EPS post
      transplant is discussed, in addition to the need for a high index of clinical
      suspicion to make the diagnosis. 

PMID- 25983928
TI  - BK virus induced nephritis in a boy with acute myeloid leukaemia undergoing bone
      marrow transplantation.
AB  - BK virus (BKV) is a human polyomavirus. The primary infection occurs typically
      without specific signs or symptoms. Almost 80% of adults are seropositive.
      Clinically relevant infections are usually limited to individuals who are
      immunosuppressed. After primary infection, BKV remains latent in the kidneys and
      can be reactivated in the setting of immunosuppression. BKV is associated with
      tubulointerstitial nephritis and ureteric stenosis in renal transplant
      recipients. Furthermore, BKV-induced haemorrhagic cystitis (HC) is a severe
      complication of bone marrow transplantation (BMT) in children and adults. A
      combination of HC and tubulointerstitial nephritis in a patient has not been
      reported so far. We report on an 11-year-old boy with acute myeloid leukaemia
      undergoing BMT. BKV infection was reactivated during post-transplant
      immunosuppressive therapy causing HC associated with tubulointerstitial
      nephritis. 

PMID- 25983929
TI  - Renal transplant malakoplakia: case report and review of the literature.

PMID- 25983930
TI  - Reversible bilateral optic disc swelling in a renal patient treated with
      nitrofurantoin.

PMID- 25983931
TI  - A 34-year-old man with membranous nephropathy, a rash, meningitis and ocular
      involvement.

PMID- 25983932
TI  - Diagnosis by inclusion.

PMID- 25983933
TI  - Thalidomide: a treatment option for bleeding GI angiodysplasias in dialysed
      patients.

PMID- 25983934
TI  - Acute abdomen and acute kidney injury: a common entity, a not so rare link?

PMID- 25983935
TI  - Acute renal failure and multiple sites of ischaemia: what is the unifying
      diagnosis?

PMID- 25983936
TI  - Hyperparathyroidism in a diabetic patient on dialysis.

PMID- 25983937
TI  - Von Hansemann cells and Michaelis-Gutmann bodies in a retroperitoneal mass.

PMID- 25983938
TI  - Purple urine bag syndrome (PUBS).

PMID- 25983939
TI  - Tracing chameleon: thallium-201 SPECT/CT for pheochromocytoma.

PMID- 25983940
TI  - Octreotide scanning in the detection of metastatic renal cell carcinoma.

PMID- 25983941
TI  - A mysterious 'homesickness'.

PMID- 25983942
TI  - STIR(ing) appearance of rhabdomyolysis.

PMID- 25983943
TI  - Rapid remission of minimal change disease with angiotensin II antagonist
      treatment in a type 1 diabetic patient with no diabetic nephropathy.

PMID- 25983944
TI  - The pattern of proteinuria following karate (Kumite) competitions.

PMID- 25983945
TI  - The effect of angiotensin type 1 receptor blockade on adhesion molecules in
      patients with IgA nephropathy.

PMID- 25983946
TI  - Pulse oximetry is useful for screening sleep apnoea syndrome in dialysis
      patients.

PMID- 25983948
TI  - Treatment of metformin-associated lactic acidosis with sustained low-efficiency
      daily dialysis.

PMID- 25983947
TI  - Cinacalcet in HIV haemodialysis patients.

PMID- 25983949
TI  - Foreword.

PMID- 25983950
TI  - Secondary hyperparathyroidism disease stabilization following calcimimetic
      therapy.
AB  - Standard therapy for secondary hyperparathyroidism (SHPT) includes dietary
      calcium supplementation, active vitamin D, and phosphate binders; however, these
      are often insufficient to allow patients to achieve their serum parathyroid
      hormone (PTH), calcium and calcium-phosphorus product (Ca * P) targets. Recent
      preclinical studies have demonstrated that treatment with type II calcimimetics
      that increase the sensitivity of the calcium-sensing receptor (CaR) to calcium
      can reverse the alterations in CaR and vitamin D receptor expression and
      parathyroid cell proliferation that are associated with SHPT. These data suggest
      that calcimimetic treatment could stabilize disease progression and improve
      maintenance of treatment goals. In clinical trials involving SHPT patients, the
      calcimimetic cinacalcet has been shown to decrease PTH, calcium, phosphorus and
      Ca * P. Significant improvements were seen regardless of initial disease
      severity, and benefits were maintained over the course of long-term therapy (up
      to 4 years), indicating effective disease stabilization. In conclusion,
      preclinical and clinical data provide both theoretical and empirical support for
      the use of calcimimetics in moderate and advanced SHPT to effectively stabilize
      disease. 

PMID- 25983951
TI  - Efficacy of early treatment with calcimimetics in combination with reduced doses
      of vitamin d sterols in dialysis patients.
AB  - Vitamin D is an important physiologic regulator of bone and mineral metabolism.
      In chronic kidney disease, reduced renal production of calcitriol contributes to
      secondary hyperparathyroidism (SHPT). Consequently, supplementation with vitamin
      D sterols is an important treatment for SHPT and its associated mineral and bone
      disorders. However, doses of vitamin D sterols required to suppress parathyroid
      hormone (PTH) secretion often promote hypercalcaemia and hyperphosphataemia.
      Therefore, there is a trade-off between reduced serum PTH and increased levels of
      serum calcium, phosphorus and calcium-phosphorus product. It has been suggested
      that treatment of SHPT with cinacalcet, a type II calcimimetic, with reduced
      doses of vitamin D sterols could enhance achievement of calcium and phosphorus
      treatment targets while maintaining goals for PTH. Recent clinical trials have
      evaluated this hypothesis and demonstrated that treatment with cinacalcet in
      combination with reduced doses of vitamin D sterols is an effective treatment for
      the management of SHPT. 

PMID- 25983952
TI  - The Pathophysiology of Secondary Hyperparathyroidism and the Consequences of
      Uncontrolled Mineral Metabolism in Chronic Kidney Disease: The Role of COSMOS.
AB  - The development of secondary hyperparathyroidism (SHPT) is a common complication
      of chronic kidney disease. SHPT develops as a consequence of mineral metabolism
      disturbances and is characterized by elevated serum parathyroid hormone (PTH) and
      parathyroid hyperplasia. Evidence suggests that SHPT contributes to the
      development of vascular calcification and cardiovascular disease, as well as to
      the development of renal osteodystrophy. The elevated serum calcium, phosphorus,
      calcium-phosphorus product and PTH that accompany SHPT have been independently
      associated with an increased relative risk of mortality. Despite the danger that
      these risks represent, achieving control of mineral metabolism in SHPT is
      difficult. Recent evidence from the Current Management of Secondary
      Hyperparathyroidism: Multicentre Observational Study has shown that fewer than 1
      in 10 haemodialysis patients simultaneously meet their National Kidney Foundation
      Kidney Disease Outcomes Quality Initiative targets for serum calcium, phosphorus,
      calcium-phosphorus product and PTH with standard treatments. There is therefore
      an urgent need for new strategies and novel pharmacologic therapies that improve
      control of mineral metabolism and PTH secretion in SHPT and thus reduce the
      mortality associated with this condition. 

PMID- 25983953
TI  - A new paradigm for the treatment of secondary hyperparathyroidism.
AB  - The global rise in chronic kidney disease makes secondary hyperparathyroidism
      (SHPT) a growing medical concern. Conventional therapies for treating SHPT are
      limited and include calcium-based and calcium-free phosphate binders for reducing
      serum phosphorus and vitamin D or its analogues for simultaneous stimulation of
      calcium absorption and suppression of parathyroid hormone (PTH) gene expression.
      Control of SHPT using these therapies has typically been poor. Recent studies
      have demonstrated that use of calcimimetics that reduce PTH secretion by
      increasing the sensitivity of the parathyroid gland calcium-sensing receptor to
      circulating calcium allow improved control of serum PTH, calcium, phosphorus and
      calcium-phosphorus product. This review describes experimental data and the
      clinical rationale supporting novel strategies for the integration of
      calcimimetics with conventional therapies to improve control of SHPT. 

PMID- 25983955
TI  - Potential future uses of calcimimetics in patients with chronic kidney disease.
AB  - Cinacalcet has proven effective in the treatment of secondary hyperparathyroidism
      (SHPT) in dialysis patients, and it may also have benefits in stage 3 and 4
      chronic kidney disease (CKD). The efficacy of cinacalcet in the treatment of SHPT
      was investigated in a study of 54 patients with stage 3 and 4 CKD not receiving
      dialysis. A significant number of these patients achieved at least a 30%
      reduction in parathyroid hormone (PTH) from baseline with cinacalcet therapy
      compared with placebo (56% versus 19%; P = 0.006). Another potential use of
      cinacalcet is in the treatment of persistent hyperparathyroidism (HPT) after
      kidney transplantation. The pathophysiologic considerations for persistent HPT in
      patients who have undergone renal transplantation are different from those in
      stage 3 and 4 CKD. Post-transplant patients with normal graft function often
      present with hypercalcaemia, low serum phosphorus and persistently elevated
      levels of PTH. In eight small open-label studies including a total of 83 patients
      with persistent HPT after successful kidney transplantation, cinacalcet treatment
      effectively corrected hypercalcaemia and significantly reduced elevated PTH
      levels. These studies suggest that cinacalcet therapy is an effective therapy in
      controlling hyperparathyroidism in patients with stage 3 and 4 CKD and in post
      transplant patients with persistent hyperparathyroidism. 

PMID- 25983959
TI  - Welcome address.

PMID- 25983954
TI  - Clinical outcomes in secondary hyperparathyroidism and the potential role of
      calcimimetics.
AB  - Cinacalcet, a type II calcimimetic agent that interacts with the calcium-sensing
      receptor on the parathyroid gland and increases its sensitivity to calcium, has
      proved an effective therapy for the treatment of the biochemical derangements
      that comprise uraemic secondary hyperparathyroidism. These patients experience
      high cardiovascular attrition with evidence that this is associated with vascular
      calcification, arterial stiffening and increased pulse wave velocity, and with
      some of the disturbances of bone and mineral metabolism in uraemia. Thus, it is
      possible that improved biochemical control in calcimimetic-treated patients might
      lead to better clinical outcomes. This hypothesis was investigated by
      retrospective analyses of randomized placebo-controlled phase 3 studies. The
      addition of cinacalcet to standard therapy with active vitamin D and phosphate
      binders was found to result in a 93% reduction in the rate of parathyroidectomy,
      a 54% reduction in fracture rate and 39% reduction in the rate of cardiovascular
      hospitalization, as well as improvements in some measures of quality of life.
      These encouraging results point to the need for a more robust assessment of the
      impact of cinacalcet on cardiovascular and skeletal outcomes. 

PMID- 25983956
TI  - The role of the calcium-sensing receptor in the pathophysiology of secondary
      hyperparathyroidism.
AB  - The calcium-sensing receptor (CaR), a seven-transmembrane domain receptor
      belonging to the G protein-coupled receptor family, is responsible for calcium
      mediated signalling initiated at the surface of parathyroid cells that controls
      the synthesis and secretion of parathyroid hormone (PTH). Expression of the CaR
      is downregulated in animal models of uraemia and in patients with secondary
      hyperparathyroidism (SHPT). Cinacalcet is a type II calcimimetic agent that acts
      as an allosteric modulator of CaR signalling. It has been shown in clinical
      studies to improve control of serum PTH levels and in preclinical studies to
      attenuate SHPT disease progression and parathyroid hyperplasia. Cinacalcet
      represents the first of this novel class of agents and a major advance in the
      treatment of SHPT. 

PMID- 25983961
TI  - Awards and grants.

PMID- 25983960
TI  - Paper selection committee.

PMID- 25983963
TI  - Next Congresses of the ERA-EDTA.

PMID- 25983962
TI  - Scientific programme.

PMID- 25983964
TI  - Control of severe hyperparathyroidism in dialysis patients with nodular
      hyperplasia.

PMID- 25983965
TI  - Indication and efficacy of PEIT in the management of secondary
      hyperparathyroidism.
AB  - Control of secondary hyperparathyroidism (SHPT) using active vitamin D analogues
      becomes difficult in advanced SHPT, because the enlarged parathyroid glands
      (PTGs) are resistant to medical therapy. Percutaneous ethanol injection therapy
      (PEIT) has been widely used in Japan since the 1990s as a surgical intervention
      for advanced SHPT, by selectively destroying only the enlarged glands with
      nodular hyperplasia (i.e. >0.5 cm(3), measured by ultrasonography). If there is
      only one PTG with nodular hyperplasia, PEIT will be successful with a small
      number of injections, and it then becomes possible to maintain target levels of
      parathyroid hormone by treatment with active vitamin D analogues. Recent studies
      have demonstrated that in the advanced phase of SHPT, it is desirable to perform
      PEIT when it is restricted to patients with not more than one PTG larger than 0.5
      cm(3) in terms of superior prognosis can be obtained including efficacy, low
      recurrence, and long-term remission period. 

PMID- 25983966
TI  - Medical management after parathyroid intervention.
AB  - Vitamin D or vitamin D analogues pulse therapy is seldom effective in patients
      with at least one parathyroid gland with nodular hyperplasia, and surgical
      parathyroidectomy or parathyroid intervention is indicated. In parathyroid
      interventions, especially in selective percutaneous ethanol injection therapy
      (PEIT), the enlarged parathyroid gland(s) with nodular hyperplasia is selectively
      destroyed by ethanol injection, while other glands with diffuse hyperplasia are
      managed by medical therapy. Thus, medical management, e.g., use of appropriate
      dose of vitamin D or vitamin D analogues after the PEIT procedure, is as
      important as the destruction of the hyperplastic tissue itself. Recent studies
      showed that the combination of PEIT and intravenous vitamin D pulse therapy lead
      to reduce serum PTH level and calcium-phosphorus products in haemodialysis
      patients. In this article, we focus on the importance of medical therapy after
      PEIT, and review the efficacy of the combination of PEIT and intravenous vitamin
      D pulse therapy for haemodialysis patients with secondary hyperparathyroidism. 

PMID- 25983968
TI  - Percutaneous ethanol injection therapy for advanced renal hyperparathyroidism in
      Japan: 2004 survey by the Japanese Society for Parathyroid Intervention.
AB  - Background. Marked hyperplasia of the parathyroid gland (PTG) is a characteristic
      feature of severe hyperparathyroidism in patients under chronic haemodialysis
      treatment. Percutaneous ethanol injection therapy (PEIT) is now becoming popular
      in Japan as a treatment option for secondary hyperparathyroidism (SHPT) and its
      cost is covered by the National Health Insurance (NHI) System. The Japanese
      Society for Parathyroid Intervention surveyed its membership in 2004 to revise
      the guidelines for the use of PEIT. Methods. The project was approved by the
      Executive Committee of the Society, and the primary questionnaire was addressed
      to 3268 centres (departments) affiliated with the Japanese Society for Dialysis
      Therapy. A follow-up questionnaire was sent to all the centres that responded.
      Results. Although the number of centres to which the questionnaire was sent in
      2004 was 3268, compared with 2653 in 1998, the number of responses decreased from
      1425 (53.7%) in 1998 to 962 (29.4%) in 2004. To the question of whether the
      centre performed PEIT, 114 (11.9%) answered 'Yes' and 848 (88.1%) answered 'No'
      in 2004. It was an increase from 1998 when only 83 (5.8%) of 1425 centres
      answered 'Yes'. In the 1998 survey, 612 patients underwent PEIT at 74 centres,
      and in 2004, 2098 patients underwent PEIT at 111 centres. Conclusions. PEIT may
      become the frequently performed treatment for SHPT patients who become resistant
      to medical therapy. However, the same problems as in 1998 remain unsolved; that
      is, recurrent nerve paralysis, difficulty of post-PEIT PTx and lack of evidence
      showing the long-term effectiveness of PEIT. 

PMID- 25983967
TI  - Pathophysiology of parathyroid hyperplasia in chronic kidney disease: preclinical
      and clinical basis for parathyroid intervention.
AB  - Secondary hyperparathyroidism is characterised by excessive secretion of
      parathyroid hormone and parathyroid hyperplasia, resulting in both skeletal and
      extraskeletal consequences. Recent basic and clinical studies have brought
      considerable advances in our understanding of the pathophysiology of parathyroid
      hyperplasia and have also provided practical therapeutic approaches, especially
      with regard to indications for parathyroid intervention. In this context, it is
      quite important to recognize the development of nodular hyperplasia, because the
      cells in nodular hyperplasia are usually resistant to calcitriol treatment.
      Patients with nodular hyperplasia should undergo parathyroid intervention
      including percutaneous ethanol injection therapy (PEIT). Selective PEIT of the
      parathyroid gland is an effective approach in which the enlarged parathyroid
      gland with nodular hyperplasia is 'selectively' destroyed by ethanol injection,
      and other glands with diffuse hyperplasia are then managed by medical therapy.
      With a more focused attention to applying parathyroid intervention, we can expect
      significant improvement in the management of secondary hyperparathyroidism in
      dialysis patients. 

PMID- 25983969
TI  - New clinical guidelines for selective direct injection therapy of the parathyroid
      glands in chronic dialysis patients.
AB  - In 2000, the Japanese Society for Parathyroid Intervention issued the 'Guidelines
      for percutaneous ethanol injection therapy of the parathyroid glands in chronic
      dialysis patients'. Since then, the concept of 'selective PEIT' has been well
      accepted and the number of patients treated by this method in Japan has
      increased. Recently, it has been reported that the effect of PEIT differs
      depending on the degree of nodular hyperplasia. Several new drugs have become
      available since 2000, and active vitamin D and its analogue have also been used
      for direct injection into the parathyroids. We present the new 'Guidelines for
      selective direct injection therapy of the parathyroid glands in chronic dialysis
      patients', a revised version of the 2000 Guidelines. We believe that these new
      guidelines are useful for selecting direct injection therapy in patients with
      advanced secondary hyperparathyroidism. 

PMID- 25983971
TI  - Current status of parathyroidectomy for secondary hyperparathyroidism in Japan.

PMID- 25983970
TI  - Long-term prognosis of parathyroid function in chronic dialysis patients after
      PEIT-a single-centre trial.
AB  - Background. Secondary hyperparathyroidism (SHPT) is a common complication
      observed in long-term dialysis patients. Percutaneous ethanol injection therapy
      (PEIT) of parathyroid glands (PTGs) is now established in Japan as a treatment
      option for SHPT. In this study, to elucidate the factors influencing efficacy in
      1 year and relapse following PEIT, we analysed the long-term prognosis of
      parathyroid function that is known to have the greatest effect on therapeutic
      results. Methods. The study design was a retrospective cohort study. We studied
      104 patients with SHPT, who underwent PEIT at Tokai University Hospital between
      January 1993 and December 2002, and we followed them up until January 2008. The
      effective group reached intact parathyroid hormone of 200 pg/ml or less,
      corrected calcium (Ca) of 10.5 mg/dl or less and phosphate (P) of 6.0 mg/dl or
      less. The ineffective group failed to achieve these criteria. Results. Among the
      104 patients, 66 patients (63%) fulfilled the criteria for the effective group
      within the first year of PEIT. Using the multivariate logistic regression
      analysis, the number of PTGs before PEIT was a significant risk factor to deviate
      from the criteria. At the end of the surveillance period, 31 patients (30%)
      fulfilled the criteria, and their SHPT was controlled with PEIT. Using the
      multivariate logistic regression analysis, more than three PTGs at the beginning,
      and the increase in PTGs during the observation period were significant risk
      factors to deviate from the criteria. In conclusion, superior results with PEIT
      are obtained in terms of efficacy, remission period and risk of relapse,
      regardless of the size of the gland. 

PMID- 25983972
TI  - Effects of percutaneous ethanol injection therapy on subsequent surgical
      parathyroidectomy.
AB  - Background. Renal hyperparathyroidism (RHPT) is a serious complication of long
      term dialysis treatment. Two intervention methods can be administered to treat
      RHPT, namely percutaneous ethanol injection therapy (PEIT) and a
      parathyroidectomy (PTx). PEIT is associated with a significant adverse event,
      adhesion formation. This study was performed to investigate the effect of PEIT on
      subsequent PTx. Methods. A total of 80 subjects were included in the study. The
      patients had a diagnosis of RHPT for which surgery was indicated. They were
      divided according to whether they underwent PEIT (PEIT group) or not (non-PEIT
      group). The outcomes of PTx following PEIT were evaluated. Results. There were 19
      patients in the PEIT group and 61 in the non-PEIT group. The operation time was
      significantly longer in the PEIT group but no significant differences in the
      amount of bleeding or frequency of recurrent nerve paralysis were observed. The
      intact PTH levels immediately following surgery were slightly higher in the PEIT
      group. The postoperative intact PTH levels were found to be significantly higher
      in those who received two or more courses of PEIT. The number of patients with an
      intact PTH level >60 pg/ml on postoperative Day 1 was significantly higher in the
      PEIT group. Conclusions. These findings suggested that PEIT prior to PTx can
      affect the subsequent surgical outcome due to associated adhesions and
      dissemination. For patients with a possibility of either a decreased efficacy or
      a lack of efficacy for PEIT, it is therefore important to consider PTx from the
      very beginning of the treatment. 

PMID- 25983973
TI  - Cellular changes following direct vitamin D injection into the uraemia-induced
      hyperplastic parathyroid gland.
AB  - Background. Hyperplasia of the parathyroid gland (PTG) is associated not only
      with excessive secretion of parathyroid hormone (PTH) but also with changes in
      the parathyroid cell (PTC) characteristics (i.e. hyperproliferative activity and
      low contents of vitamin D and calcium-sensing receptors). The control of PTG
      hyperplasia is most important in the management of secondary hyperparathyroidism
      (SHPT), because the advanced stage of hyperplasia is considered irreversible. For
      the better control of the PTH level in dialysis patients with such advanced SHPT,
      percutaneous vitamin D injection therapy (PDIT) under ultrasonographic guidance
      was developed and various cellular changes caused by this treatment were also
      investigated using an animal model. Methods. The PTGs of Sprague-Dawley rats,
      which had been 5/6-nephrectomized and fed a high-phosphate diet, were treated
      with the direct injections of vitamin D agents, and cellular effects focusing the
      above-mentioned characters were investigated. Results. An adequacy of the direct
      injection technique into the rats' PTGs and the successful effects of this
      treatment in various biochemical parameters were confirmed. Such characteristics
      of advanced SHPT were simultaneously improved; in particular, it was confirmed
      that this treatment may be effective in controlling PTG hyperplasia by, at least
      in part, apoptosis-induced cell death. Conclusions. A locally high level of
      vitamin D strongly may suppress PTH secretion and regress hyperplasia, which is
      involved in the induction of apoptosis in PTCs, based on the simultaneous
      improvements of cellular characters of advanced SHPT. The PTH control introduced
      by this treatment successfully ameliorated osteitis fibrosa (high bone turnover
      rate). 

PMID- 25983974
TI  - Association between long-term efficacy of cinacalcet and parathyroid gland volume
      in haemodialysis patients with secondary hyperparathyroidism.
AB  - Purpose. Secondary hyperparathyroidism with nodular hyperplasia is resistant to
      medical therapies. Cinacalcet is an effective treatment for severe secondary
      hyperparathyroidism. This multicentre retrospective study was designed to
      determine the long-term efficacy of cinacalcet in patients with nodular
      hyperplasia, the advanced type of parathyroid hyperplasia. Subjects and methods.
      The study subjects were 20 haemodialysis patients with secondary
      hyperparathyroidism. Patients with ultrasonographically confirmed large
      parathyroid glands (volume >0.5 cm(3)) were considered to have nodular
      hyperplasia (n = 8). Cinacalcet was started at the dose of 25 mg/day and titrated
      up to 100 mg/day to achieve the target intact-parathyroid hormone (iPTH) level of
      <250 pg/ml. Serum iPTH, corrected calcium, serum phosphorus, calcium * phosphorus
      product were measured and compared over the 48-week period of treatment with
      cinacalcet in all 20 patients and over 120 weeks in 6 of the patients (2 with
      nodular hyperplasia and 4 with non-nodular hyperplasia). We also examined the
      achievement rate of K/DOQI guideline treatment targets. The dosages of vitamin D
      preparation, sevelamer hydrochloride and calcium- containing phosphate binder
      were adjusted for the above target values. Results. iPTH levels were
      significantly lower at 48 weeks in both groups. However, corrected calcium
      levels, serum phosphorus levels and calcium phosphorus products were within the
      target values in the non-nodular hyperplasia group (n = 12), while the target
      value could not be achieved in the nodular hyperplasia group. In the long-term
      follow-up group, the levels of iPTH, corrected calcium, serum phosphorus and
      calcium * phosphorus products were significantly higher in nodular hyperplasia
      than in non-nodular hyperplasia. Conclusion. Our study suggests that cinacalcet
      lacks long-term efficacy in nodular hyperplasia, especially for controlling serum
      calcium and phosphorus levels. 

PMID- 25983975
TI  - Reversed whole PTH/intact PTH ratio as an indicator of marked parathyroid
      enlargement: five case studies and a literature review.
AB  - Parathyroid hormone (PTH) levels detected by intact PTH assays are generally
      higher than those detected by the whole PTH assay because the latter does not
      detect non-(1-84) PTH fragments, mainly PTH (7-84). Rare exceptions to this rule
      have been reported in patients with severe primary or secondary
      hyperparathyroidism and parathyroid carcinoma. Overproduction of an N-form of PTH
      other than PTH (1-84) has been observed in the sera of these patients. We report
      five additional cases with the reversed whole PTH/intact PTH ratio associated
      with severe hyperparathyroidism in haemodialysis patients. Three patients
      demonstrated enlargement of a single hypervascular gland, whereas the other two
      had undergone surgical parathyroidectomy and later showed recurrent
      hyperparathyroidism due to progressive autograft hyperplasia. In the case of a
      single enlarged gland, the pathological pattern and heterogeneous expression of
      parathyroid adenomatosis 1/cyclin D1 suggested it to be a single nodule of
      uraemic hyperparathyroidism rather than sporadic primary adenoma. These cases
      suggested that the reversed whole PTH/intact PTH ratio could be an indicator of
      marked parathyroid enlargement. Further studies are required to elucidate the
      clinical significance of the reversed whole PTH/intact PTH ratio in haemodialysis
      patients. 

PMID- 25983976
TI  - The whole-PTH/intact-PTH ratio is a useful predictor of severity of secondary
      hyperparathyroidism.
AB  - Background. The newer parathyroid hormone (PTH) assay, whole-PTH, uses an
      antibody that binds the region harbouring the first amino acid, making it
      specific for the complete molecule, 1-84-PTH. Especially among dialysis patients,
      it has been reported that the level of whole-PTH can be calculated as ~60% of
      their intact-PTH value. In addition, since 1-84-PTH is part of intact-PTH, the
      whole-PTH/intact-PTH ratio should not theoretically exceed 1. However, an
      abnormally high 1-84-PTH/intact-PTH ratio is reported in a few patients with
      parathyroid carcinoma, primary hyperparathyroidism and secondary
      hyperparathyroidism. In this study, we examined the correlation between the 1-84
      PTH/intact-PTH ratio and the severity of hyperparathyroidism in patients on
      haemodialysis (HD). Patients and methods. The study population comprised 196 HD
      patients (males 113, females 83, age 67.4 +/- 13.6 years, HD period 8.1 +/- 7.3
      years; mean +/- SD). The whole-PTH/intact-PTH ratio was compared in patients with
      high PTH levels (intact-PTH >=300 pg/ ml; high PTH group, n = 32), moderate PTH
      levels (intact-PTH >150-<300 pg/ml; moderate PTH group, n = 50) and low PTH
      levels (intact-PTH <150 pg/ml; low PTH group, n = 114). The ratio was also
      compared in 25 patients with at least one enlarged gland >0.5 cm(3) suggesting
      nodular hyperplasia, as determined by power Doppler ultrasonography (hyperplasia
      group) with seven patients without enlarged gland (non-hyperplasia group) and six
      patients who had undergone total parathyroidectomy (post-PTx group). Results. The
      whole-PTH/intact-PTH ratio of the high PTH group (0.68 +/- 0.1) was significantly
      higher than those of the moderate (0.61 +/- 0.1, P < 0.001) and low (0.52 +/-
      0.1, P < 0.001) groups. Moreover, the ratio was significantly higher in the
      hyperplasia group (0.70 +/- 0.1) than those in the non-hyperplasia group (0.59 +/
      0.1, P < 0.05) and post-PTx group (0.456 +/- 0.12, P < 0.001). Conclusions. The
      whole-PTH/intact-PTH ratio correlated with the severity of hyperparathyroidism.
      Our results suggest that the ratio might be a useful predictor of severity of
      secondary hyperparathyroidism in HD patients. 

PMID- 25983977
TI  - Clinical significance of parathyroid intervention on CKD-MBD management.
AB  - Recently published 'Guidelines for the management of secondary
      hyperparathyroidism in chronic dialysis patients' by the Japanese Society for
      Dialysis Therapy advocate that percutaneous ethanol injection into enlarged
      glands, which has been considered as the only alternative to parathyroidectomy
      (PTx), should be indicated in patients with a single enlarged parathyroid gland
      (estimated volume >500 mm(3), or estimated major axis >10 mm), and that PTx
      should be recommended in patients with multiple enlarged glands. Cinacalcet
      cannot achieve optimal control of chronic kidney disease-mineral bone disorder in
      all patients, and parathyroid intervention will be required in a considerable
      number of patients with refractory secondary hyperparathyroidism. 

PMID- 25983978
TI  - Foreword.

PMID- 25983979
TI  - Different treatment options in peritoneal dialysis.
AB  - Patients with end-stage renal disease (ESRD) are placed on dialysis while they
      await kidney transplantation. The mortality rate among patients with ESRD is
      high. This review outlines the importance of preservation of residual renal
      function (RRF) and supports the idea of the integrated care approach to uraemia
      where patients start on peritoneal dialysis (PD). 

PMID- 25983981
TI  - Prevalence of nephropathy in the German diabetes population-Is early referral to
      nephrological care a realistic demand today?
AB  - In Germany, diabetes mellitus in the general population has increased to ~8
      million people. The implication of this trend for future nephrological care is
      not well known, as data on this issue are rather limited. Results from different
      population-based studies suggest that microalbuminuria in diabetic patients is
      present in 20-30% of the cases. Findings from the diabetes disease management
      programme in the North-Rhine area revealed the prevalence of chronic kidney
      disease (CKD) stage II in half of the participants (CKD stage III was present in
      ~20%). Only a small proportion of this cohort (~1-2%) will reach end-stage renal
      failure, probably due to the excess mortality risks attributed to advanced kidney
      disease. Results from the QUASI-Niere registry, which reports on renal
      replacement therapy in Germany, indicate almost constant incidence and prevalence
      rates of diabetes in the last 5 years (30.6-34.2% and 23.6-27.1%, respectively).
      The high percentages of early stages of CKD in the diabetes population indicate a
      potentially high burden of future nephrological care, especially if patients are
      referred to nephrologists at an early stage. In reality, in nephrological care,
      bearing this burden is impossible without expanding the resources for this
      patient group. 

PMID- 25983980
TI  - Clinical effects of icodextrin in peritoneal dialysis.
AB  - Objective. This study reviews the relevant publications on the clinical effects
      of icodextrin in peritoneal dialysis (PD). Design. The study provides a
      systematic review of the literature (MEDLINE search with icodextrin as the
      keyword). Results. Icodextrin induces sustained transcapillary ultrafiltration
      during long dwell periods. It also stimulates increased removal of sodium by the
      peritoneal membrane, reduction of extracellular water (ECW) and total body water
      (TBW). Effects of icodextrin on blood pressure control and residual renal
      function are discrepant. Icodextrin induces a reduction in the formation of
      advanced glycation end-products, while the longitudinal changes in the peritoneal
      membrane transport are less prominent. Conclusions. Use of icodextrin in PD
      improves the sodium and fluid balance. Icodextrin is potentially more
      biocompatible, when compared with the conventional glucose solutions. The side
      effects are rare. 

PMID- 25983982
TI  - Peritoneal dialysis catheter placement technique and complications.
AB  - Background. This review describes the peritoneal dialysis (PD) catheter
      implantation techniques for the treatment of PD. The PD catheter-related
      complications still cause significant morbidity and mortality, resulting in the
      necessity to switch to haemodialysis (HD) treatment. Methods. Several catheter
      insertion techniques, using an open surgical approach, laparoscopic and
      percutaneous techniques have been employed, with their specific early and late
      complications and failure rates. Results. Despite the similar outcomes of open
      surgical versus laparoscopic techniques from randomized studies, the laparoscopic
      insertion has the major advantage of correct catheter positioning in the lower
      abdomen, with the possibility of adhesiolysis. The minimal invasive percutaneous
      insertion bears the risk of bowel perforation and catheter malpositioning, and
      the outcome of this technique is strongly related to the experience of the
      surgeon. The major complications of these implantation techniques, like bleeding,
      dialysate leakage and catheter malpositioning, and their management are discussed
      in our study. Late peritonitis remains the major drawback of PD treatment, with
      the need of temporary or permanent changeover to the HD treatment in 10% of the
      patients. Conclusions. Enrichment of the physician's interest and experience,
      along with a multidisciplinary approach to outline the optimal strategy of PD
      catheter insertion and complication of the treatment, may improve the patients'
      survival and decrease the morbidity. 

PMID- 25983984
TI  - Dialysate as food as an option for automated peritoneal dialysis.
AB  - Protein-energy malnutrition is frequently found in dialysis patients. Many
      factors play a role in its development including deficient nutrient intake as a
      result of anorexia. Peritoneal dialysis (PD) solutions containing a mixture of
      amino acids and glucose in an appropriate ratio could serve as a source of food.
      The authors of this article found that such a dialysis solution when administered
      to fasting patients who were on nightly automated peritoneal dialysis (APD), as
      part of a regular dialysis schedule, induced an acute anabolic effect. Also in PD
      patients in the fed state, dialysis solutions containing both amino acids and
      glucose were found to improve protein metabolism. It appears that the body
      responds similar to intraperitoneal and oral amino acid:dialysate as food. Like
      dietary proteins, intraperitoneal amino acids can bring about generation of
      hydrogen ions and urea as a result of oxidation. No rise of serum urea levels was
      found and serum bicarbonate remained within the normal range when a total buffer
      concentration of 40 mmol/L in the mixture was used. The use of this approach may
      be an option for PD patients who cannot fulfil dietary recommendations. 

PMID- 25983983
TI  - Monitoring of the peritoneal membrane.
AB  - Background. Indirect methods can be used to provide valuable information about
      peritoneal structure and function for the indirect analysis of peritoneal
      membrane. Methods. The focus of this paper will be on the commonly available
      tools for this purpose. First, the value and clinical relevance of CA125 as a
      marker of mesothelial cell mass in peritoneal effluent will be evaluated.
      Thereafter, monitoring the peritoneal membrane by using its properties to
      transport solutes and water will be discussed. Results. The data obtained can be
      useful for tailoring dialysis adequacy, analysis of clinical problems such as
      ultrafiltration failure or to predict the development of peritoneal sclerosis. 

PMID- 25983985
TI  - The relationship between effluent potassium due to cellular release, free water
      transport and CA125 in peritoneal dialysis patients.
AB  - Background. Recently, we found evidence of effluent potassium (K(+)) additional
      to diffusion and convection, suggesting cellular release (CR). Its relationship
      with free water transport (FWT) in stable peritoneal dialysis (PD) patients
      suggested an effect of hypertonicity of the dialysis solution leading to cell
      shrinkage. The aim of the present study was to reproduce these findings in groups
      according to PD duration and to further investigate the role of mesothelial cells
      in the observed phenomenon. Methods. Standard peritoneal permeability analyses
      done with 3.86% glucose were analysed cross-sectionally in three different
      groups: short-term (n = 53) 0-2 years PD treatment; medium-term (n = 24) 2-4
      years PD and long-term (n = 26) > 4 years PD. Results. The time courses for FWT
      and cellular release of K(+) (CR-K(+)) during the dwell were not significantly
      different among the groups. Cancer antigen (CA) 125 was highest in the short-term
      group (P <= 0.02) and had a strong positive correlation with mass transfer area
      coefficient of creatinine (MTAC-creatinine) only in the short-term group (r =
      0.62, P <= 0.01). CA125 had no relationship with either CR-K(+) or FWT, except
      for negative relationships in the short-term group (CR-K(+), r = -0.41, P <=
      0.05; FWT, r = -0.54, P <= 0.05). Conclusion. We conclude that the correlation of
      CA125 and MTAC-creatinine is dependent on PD duration and underlines the in vitro
      observation that mesothelial cells produce vasoactive substances that may
      increase the peritoneal surface area. However, CA125 is not directly related to
      CR-K(+) or FWT. Therefore, the relationship between FWT and CR-K(+) is likely to
      reflect hypertonic cell shrinkage, regardless of the duration of PD, and confirms
      our earlier findings. 

PMID- 25983986
TI  - Conventional versus biocompatible peritoneal dialysis fluids: more questions than
      answers?
AB  - The most important challenge in peritoneal dialysis (PD) is long-term
      preservation of peritoneal membrane structure and function. Introduction of
      dialysis fluids into the peritoneal cavity induces changes. These changes are
      related to duration of dialysis, occurrence of peritonitis and components of the
      dialysis solution. Bioincompatibility is considered to be the major cause of the
      development of morphological changes of the peritoneal membrane. pH neutral PD
      fluids that are low in glucose degradation products (GDP) seem to better preserve
      the peritoneal membrane and have less systemic effects than the conventional
      ones. However, the long-term effects are not clear. An overview of the effects of
      conventional PD fluids and glucose-based PD fluids with neutral pH in ex vivo and
      in vivo animal and clinical studies is presented. 

PMID- 25983987
TI  - Future technologies and techniques in peritoneal dialysis-opportunities and
      challenges ahead.
AB  - In the last 5 years, we have started to witness the emergence of new technologies
      and techniques that offer the potential for improved patient outcomes but which
      often still lack clinical demonstration and/or confirmation in well-designed,
      multicentre studies. These include biocompatible solutions, glucose sparing
      regimens, low-sodium solutions, bimodal solution formulations and continuous flow
      peritoneal dialysis (CFPD). This review discusses the potential benefits
      ascribable to each of these technologies and an analysis of the challenges that
      have to be surmounted before anyone of these candidate technologies can be
      declared as established. The demonstration of either hard clinical endpoints or
      validated surrogate endpoints is very feasible in terms of sample size
      requirements for some outcome measures, such as preservation of RRF, but will be
      much more challenging for other endpoints such as preservation of UF capacity. 

PMID- 25983989
TI  - Differences between physicians in the likelihood of referral and acceptance of
      elderly patients for dialysis influence of age and comorbidity.
AB  - Background. Incidence of dialysis in elderly patients in the Netherlands is low
      compared to other countries. This study aims to assess the impact of patients'
      age and comorbidity on the likelihood of referral and acceptance of patients for
      dialysis and whether this is affected by physician characteristics. Methods. A
      vignette study was performed on 209 primary care physicians, 162 non-nephrology
      specialists and 20 nephrologists working in northern Netherlands. Physicians were
      offered six vignettes concerning case reports of patients with end-stage renal
      disease (ESRD) and varying comorbidities or circumstances and asked about the
      likelihood of referral/acceptance of the patient in the given circumstances.
      Results. The likelihood of referral within groups of physicians varied widely,
      especially within the group of primary care physicians and non-nephrology
      specialists, but was not affected by characteristics of the physicians. The
      likelihood of referral or acceptance of patients for dialysis depended on the
      patient's age, and type and severity of comorbidity. In general, primary care
      physicians and non-nephrology specialists were less likely to refer than
      nephrologists were willing to accept. Differences within and between groups of
      physicians to accept or refer were larger for 80-year-old patients than for 65
      year-old patients. The differences were wider concerning patients with less
      severe shortness of breath and cognitive impairments and more severe diabetes and
      social impairments. Hardly any differences were found for patients with cancer.
      Conclusion. Patients' age and comorbidities affect the likelihood of referral.
      Differences between groups of physicians suggest that there is insufficient
      agreement on the extent to which these factors should affect the
      referral/acceptance of patients for dialysis. These findings underline the need
      for more research into circumstances under which patients might benefit from
      dialysis. Guidelines should be developed to improve the referral of elderly and
      less healthy patients. 

PMID- 25983988
TI  - Effects of reducing the lactate and glucose content of PD solutions on the
      peritoneum. Is the future GLAD?
AB  - Background. Long-term peritoneal dialysis (PD) may lead to functional and
      morphologic changes in the peritoneal membrane, probably because of the
      continuous exposure to conventional dialysis solutions. Methods. The morphologic
      changes include neoangiogenesis and fibrosis. The authors of this article
      developed a long-term peritoneal exposure model in rats, in which the
      morphological alterations could be induced after daily peritoneal infusion of a
      3.86% glucose/lactate-buffered conventional PD solution. Results and Conclusions.
      In the present article, a review of the model and of the results obtained with
      various available and experimental solutions is given. It appeared that high
      lactate concentrations contributed to the glucose-induced neoangiogenesis by
      pseudohypoxia. Glucose degradation products were probably more important in the
      induction of peritoneal fibrosis. The promising results of a combination of amino
      acids, glycerol and glucose, each in a low concentration, buffered with either
      pyruvate or bicarbonate/lactate, are presented and discussed. The combination of
      glycerol, amino acids and dextrose, dissolved in a bicarbonate/lactate buffer
      (GLAD), may be an option for a new generation of dialysis fluids. 

PMID- 25983990
TI  - Treatment of severe ultrafiltration failure with nonglucose dialysis solutions in
      patients with and without peritoneal sclerosis.
AB  - Introduction. Ultrafiltration failure (UFF) in peritoneal dialysis (PD) patients
      is a reflection of changes in the peritoneal membrane, which can include
      mesothelial damage, neoangiogenesis, and occasionally, peritoneal fibrosis. These
      structural changes are probably induced by the use of bioincompatible dialysis
      solutions. Therefore, we investigated the effects of the treatment with a
      combination of nonglucose dialysis solutions in patients with severe UFF.
      Methods. Ten patients with UFF (net ultrafiltration <400 mL/4 h on 3.86% glucose)
      were treated with a combination of glycerol and icodextrin with or without amino
      acid-based dialysis solutions for 3 months. Four of them were diagnosed with
      encapsulating peritoneal sclerosis (PS), proven by peritoneal biopsies. Standard
      peritoneal permeability analyses (SPA), using 3.86% glucose, were performed, and
      dialysate CA125 appearance rate (AR-CA125) was analysed at the start, after 6
      weeks and after 12 weeks. PS and non-PS patients were compared. Results. One
      patient underwent transplant after 6 weeks, one was withdrawn from PD because of
      clinical signs of encapsulating PS before the 3-month period ended. PS patients
      had been treated with PD for a longer duration than the non-PS patients (102
      versus 52 months, P = 0.05), but no differences in baseline transport parameters
      or AR-CA125 were present. During the study, no differences were observed for
      transport characteristics when the results of the whole group at 6 and 12 weeks
      were compared to baseline. For the non-PS patients, however, a significant
      increase in the transcapillary ultrafiltration rate (from 2.2 mL/min to 2.6
      mL/min, P < 0.05) and a decrease in the MTAC creatinine (from 14.3 mL/min to 12.6
      mL/min, P < 0.05) were found after 6 weeks of glucose-free treatment. Free-water
      transport, measured as the maximum dip in the dialysate-to-plasma ratio of sodium
      and as the transport through the ultrasmall pores in the first minute, tended to
      improve, but this difference did not reach significance. In addition, the AR
      CA125 increased significantly (from 2.8 U/min to 16.1 U/min, P < 0.05). Continued
      treatment did not reach statistical difference even after 3 months. No changes
      were observed in the PS patients. Conclusions. In the present study, an
      improvement of UFF in the non-PS patients was obtained by withdrawal of glucose
      based dialysis solutions. The abnormalities in PS patients are probably
      irreversible. Early withdrawal of glucose-based dialysis solutions or at least a
      marked reduction in glucose exposure should be considered in UFF patients, but
      the identification of the patients who would benefit most needs further studies. 

PMID- 25983991
TI  - Optimal predialysis care.
AB  - Management of severe chronic kidney disease (CKD) involves dealing with medical,
      nursing and psychosocial problems and therefore warrants support from a
      multidisciplinary team. In the Kidney Disease Outcomes Quality Initiative (KDOQI)
      classification system of CKD, preparation for renal replacement therapy has been
      recommended in CKD stage 4, characterized by a reduction in the estimated
      glomerular filtration rate (GFR) of <30 ml/min. In this article we share our
      approach to perfecting predialysis care. Tools are given to make an estimation of
      the progression of kidney disease. Also the prevention and treatment of metabolic
      complications and cardiovascular risk management are summarized. Finally, the
      possibilities for dialysis but even more important, aiming for pre-emptive
      transplantation, are being discussed. Using a multidisciplinary integrated care
      approach predialysis care has come of age. 

PMID- 25983992
TI  - Make the grade for Wegener's granulomatosis after kidney transplantation.
AB  - Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is a well
      described cause of multiple organ involvement including rapidly progressive pauci
      immune crescentic glomerulonephritis. Kidney transplantation (KTx) is considered
      the treatment of choice in patients with end-stage renal disease (ESRD) due to
      AAV. Patient and graft survival in AAV after KTx is favourable and comparable
      with other non-diabetic causes of ESRD. While relapse of AAV is high in dialysis
      patients (up to 50%), it decreases after KTx (8.6-22.2%). Yet, relapse may occur
      at any time after KTx and transplant involvement has been documented in at least
      25 cases. Therapeutic guidelines for the management of AAV after KTx do not exist
      and clinical management is a controversial discussion. We present two unusual
      cases of young males with smouldering AAV who recently underwent KTx at our
      hospital. Case 1 experienced repeated relapses after KTx and was finally
      successfully treated with rituximab. Case 2 received rituximab pre-emptively
      before living kidney donation and remained free of flairs. Prompted by theses two
      cases, we reviewed the literature focusing on the right point of time for
      transplantation, risk assessment, role of antineutrophil cytoplasmic antibodies,
      clinical presentation of flairs and immunosuppression in smouldering Wegener's
      granulomatosis (WG) and in relapse, including individualized treatment with
      rituximab. 

PMID- 25983993
TI  - The use of vitamin D analogues in chronic kidney diseases: possible mechanisms
      beyond bone and mineral metabolism.
AB  - Chronic kidney disease (CKD) is a common and costly medical condition, and
      currently available therapeutic options remain unsatisfactory. Vitamin D
      analogues are widely used for the bone and mineral disorder associated with CKD.
      However, accumulating evidence suggests that vitamin D analogues may have actions
      other than their effects on bone and mineral metabolism. In this article, we
      review the following aspects on the use of vitamin D analogues for the treatment
      of CKD: (1) epidemiological studies showing that patients with late-stage CKD
      have better survival than untreated patients; (2) animal studies showing that
      vitamin D analogues may retard the progression of CKD; (3) human studies on the
      anti-proteinuric and possibly renal protecting effects of vitamin D analogues in
      CKD and (4) the potential mechanisms of its therapeutic benefit. Nonetheless,
      definitive proof of the clinical benefits by randomized control trial would be
      necessary before one could advocate the routine use of vitamin D analogues for
      the treatment of CKD patients. 

PMID- 25983995
TI  - Hypokalaemia and dysmorphia, is there a link?
AB  - A 15-year-old boy with quadriplegia and facial dysmorphia was referred to the
      emergency room. This was his first episode of tetraplegia. One maternal uncle had
      exhibited the same manifestation 20 years before. Blood test revealed severe
      hypokalaemia and mild hypocalcaemia. The clinical diagnosis revealed an Andersen
      Tawil syndrome. Molecular tools allowed us to make the diagnosis of familial
      hypokalaemic periodic paralysis type 1 associated with a de novo 22q11.2
      microdeletion syndrome. Our case report emphasizes the importance of molecular
      diagnosis in genetic diseases. 

PMID- 25983994
TI  - The future of European Nephrology 'Guidelines'-a declaration of intent by
      European Renal Best Practice (ERBP).

PMID- 25983996
TI  - Rituximab in two cases of Goodpasture's syndrome.
AB  - We describe the effects of rituximab in two patients with refractory
      Goodpasture's syndrome. After one single 1000 mg dose administration, rituximab
      did not appear to improve renal function in either of our cases. Polyoma virus
      negative leukoencephalopathy, a probable toxic side effect of rituximab, was seen
      in our first patient. 

PMID- 25983997
TI  - Remission of membranoproliferative glomerulonephritis associated with a
      noncirrhotic portosystemic shunt after percutaneous transhepatic portal vein
      embolization.
AB  - We present a case of a 75-year-old man with nephrotic syndrome and renal
      insufficiency caused by immune complex-mediated secondary membranoproliferative
      glomerulonephritis. He developed hepatic encephalopathy. A congenital
      portosystemic shunt was identified, indicating a diagnosis of
      membranoproliferative glomerulonephritis with noncirrhotic portosystemic shunt.
      Proteinuria resolved after shunt ratio reduction by percutaneous transhepatic
      portal vein embolization. Renal function and histopathological findings improved
      without immunosuppressive therapy. This case emphasizes the role of a high shunt
      ratio and reduced hepatic clearance of circulating immune complexes in such
      nephropathy. Membranoproliferative glomerulonephritis with a shunt may cause
      refractory nephrotic syndrome, but embolization is effective. 

PMID- 25983998
TI  - A case of tubulointerstitial nephritis in IgG4-related systemic disease with
      markedly enlarged kidneys.
AB  - IgG4-related systemic disease, including autoimmune pancreatitis, is a multi
      organ disorder characterized by elevated serum immunoglobulin G4 (IgG4)
      concentration and IgG4-positive plasma cell infiltration. We report the case of a
      67-year-old man with IgG4-related tubulointerstitial nephritis, presenting with
      markedly enlarged kidneys and renal dysfunction. The serum IgG4 level was
      elevated with 4200 mg/dl and pathological examination revealed patchy, clearly
      fringed areas of IgG4-positive plasma cell infiltration and advanced fibrosis in
      the renal parenchyma, perirenal tissue and lymph nodes. With oral prednisolone at
      a dose of 60 mg daily, a contraction of the kidneys and an improvement of renal
      function were observed. No recurrence of the disease was observed during the
      reduction of prednisolone to 2 mg daily over 4 years. 

PMID- 25983999
TI  - Recovery of renal function after delayed percutaneous dilation of a subtotal in
      stent restenosis of the renal artery in a left solitary kidney.
AB  - In-stent restenosis of a previously atherosclerotic renal artery stenosis
      initially treated with endovascular stenting may progress to subtotal occlusion
      and loss of renal function. The clinical course of an acute occlusion is mainly
      acute oligo-anuric renal failure. Therefore, rapid diagnosis and treatment are
      critical for renal survival. Even after successful endovascular treatment, a
      close clinical monitoring, and optimized medical treatment including sufficient
      blood pressure control, lipid lowering and platelet inhibition, is mandatory to
      prolong the preservation of renal function. Here we present a patient with
      subtotal in-stent stenosis affecting the left solitary kidney and recovery of
      renal function 24 h after the revascularization procedure. 

PMID- 25984000
TI  - Life-threatening rectal bleeding due to cytomegalovirus colitis in a
      haemodialysis patient.
AB  - Cytomegalovirus (CMV) disease is a well-recognized complication in
      immunocompromised patients such as renal transplant recipients, occurring due to
      reactivation of latent infection or primary infection. It is, however, uncommon
      in immunocompetent patients. We report a haemodialysis patient who presented with
      pyrexia and life-threatening rectal bleeding due to CMV colitis, who had none of
      the classical risk factors for CMV disease, although was at risk. We review the
      literature surrounding CMV colitis in immunocompetent patients. This case
      highlights the importance of considering unusual causes for the common
      presentation of rectal bleeding in vulnerable patient populations. 

PMID- 25984001
TI  - Late recovery of renal failure after autologous haematopoietic stem cell
      transplantation for multiple myeloma: a report of two cases.
AB  - Acute renal failure is a frequent feature in patients with multiple myeloma (MM).
      MM-related renal insufficiency may improve after autologous haematopoietic stem
      cell transplantation (autoHSCT) even in patients initially requiring dialysis.
      Herein, we report on two unusual cases of late improvement in renal function
      occurring over more than 5 years after autoHSCT for MM. Clinicians must be aware
      that slow and progressive improvement in renal function may occur over years in
      patients with MM-associated renal failure. Our data underline the need for an
      aggressive treatment, including autoHSCT, in MM patients presenting with severe
      renal dysfunction. 

PMID- 25984002
TI  - High-grade urothelial carcinoma in a kidney transplant recipient with BK virus
      infection.
AB  - Bladder malignancy in the kidney transplant recipient is rare and compared with
      the general population tends to be of high grade and have an aggressive clinical
      course. In this report, we describe a case of urothelial carcinoma developing in
      a kidney transplant recipient 6 years after the diagnosis of polyomavirus
      nephropathy (PVN). BK virus (BKV) DNA was identified in urine and serum by PCR.
      The diffuse strong staining of SV40 T-antigen and p53 within both the in situ and
      invasive carcinoma suggest that BKV may play a role in the oncogenic pathway in
      this clinical setting. 

PMID- 25984003
TI  - Life-threatening adenovirus infection in a kidney transplant recipient.

PMID- 25984004
TI  - Oxaliplatin-induced acute renal failure presenting clinically as thrombotic
      microangiopathy: think of acute tubular necrosis.

PMID- 25984005
TI  - Kidney packed with fat, pus and stone-xanthogranulomatous pyelonephritis.

PMID- 25984006
TI  - Massive and rapid left ventricular calcification.

PMID- 25984007
TI  - Cutaneous horn at the puncture site of arteriovenous fistula in a haemodialysis
      patient.

PMID- 25984008
TI  - Renal impairment resulting from hypothyroidism-or impaired estimated glomerular
      filtration rate in a patient with hypothyroidsm.

PMID- 25984009
TI  - End-stage renal disease (ESRD) contributes to the increasing prevalence of herpes
      zoster.

PMID- 25984010
TI  - Hydrochlorothiazide-induced tubulointerstitial nephritis in a patient with Dent
      disease.

PMID- 25984011
TI  - Comment on: 'Lanthanum carbonate possibly responsible for acute liver failure in
      a patient with Child-Pugh stage A liver cirrhosis'.

PMID- 25984012
TI  - Clinical management of disturbances of calcium and phosphate metabolism in
      dialysis patients.
AB  - Management of chronic kidney disease-mineral bone disorder can be difficult in
      renal patients. This review aims to explain why the control of disturbed calcium,
      phosphate, parathyroid hormone and vitamin D metabolism is important in dialysis
      patients. The methods available to regulate these parameters include diet,
      phosphate binders, dialysate calcium, native vitamin D, active vitamin D
      derivatives and calcimimetics. An overview of current treatment guidelines will
      be discussed. 

PMID- 25984013
TI  - The times they are a changin'-the Internet and how it affects daily practice in
      nephrology.

PMID- 25984014
TI  - A case of bovine ketoacidosis in a lactating woman.
AB  - A 36 year-old 5 weeks postpartum lactating woman presented to the emergency room
      with severe nausea and vomiting for 48 hours. The patient was found to be in non
      diabetic ketoacidosis with a serum pH 6.9 and a HCO3 of <5mEq/L. This condition
      rapidly improved with the administration of intravenous dextrose and bicarbonate
      and with the cessation of breast feeding. The course and pathophysiology of the
      rarely described phenomenon of bovine ketosis in a human is discussed here. 

PMID- 25984015
TI  - Baking soda induced severe metabolic alkalosis in a haemodialysis patient.
AB  - Metabolic alkalosis is a rare occurence in hemodialysis population compared to
      metabolic acidosis unless some precipitating factors such as nasogastric suction,
      vomiting and alkali ingestion or infusion are present. When metabolic alkalosis
      develops, it may cause serious clinical consequences among them are sleep apnea,
      resistent hypertension, dysrhythmia and seizures. Here, we present a 54-year-old
      female hemodialysis patient who developed a severe metabolic alkalosis due to
      baking soda ingestion to relieve dyspepsia. She had sleep apnea, volume overload
      and uncontrolled hypertension due to metabolic alkalosis. Metabolic alkalosis was
      corrected and the patient's clinical condition was relieved with negative
      bicarbonate hemodialysis. 

PMID- 25984016
TI  - Anti-GBM antibody disease sans crescents with thrombotic microangiopathy.
AB  - We report a case of a 38-year-old male with acute renal failure, elevated anti
      glomerular basement membrane (anti-GBM) antibody titres, bilateral nodular lung
      opacities and hypertension. In the renal biopsy examination, whereas direct
      immunofluorescence revealed significant peripheral linear deposits of IgG typical
      of anti-GBM antibody disease (Goodpasture's disease), eosin-haemotoxylin staining
      showed glomerular and vascular changes typical of thrombotic microangiopathy
      (TMA) and without crescents. We postulate that the TMA was responsible for the
      acute renal failure and that antibodies, though demonstrable, were not adequate
      at the site of the glomerular basement membrane to elicit a crescentic response,
      because of occlusion of the vascular lumina by the thrombotic process. The
      patient remained dialysis dependent at a 3-month follow-up. 

PMID- 25984017
TI  - C1q nephropathy: a true immune complex disease or an immunologic epiphenomenon?
AB  - We describe a 16-year-old Caucasian boy who presented with steroid-sensitive
      nephrotic syndrome aged 2 years. His clinical course was one of frequent relapses
      and severe steroid dependence. To manage this, he was sequentially treated with
      levamisole, then oral cyclophosphamide before being started on ciclosporin. A
      renal biopsy performed prior to commencement of ciclosporin confirmed minimal
      change disease on light microscopy. The immunohistochemistry and electron
      microscopy findings were in keeping with this. His complement levels were normal
      and his lupus serology negative. He remained on ciclosporin therapy for 8 years
      and had two further renal biopsies to detect ciclosporin-induced renal damage.
      Both biopsies showed evidence of increasing amounts of C1q deposition on
      immunohistochemistry and the presence of immune deposits on electron microscopy.
      As he had continued negative lupus serology, this was compatible with a diagnosis
      of C1q nephropathy. In addition both biopsies had changes compatible with chronic
      mild ciclosporin nephrotoxicity. This case is the first report describing in
      detail a paediatric patient with evolving C1q nephropathy who was treated
      successfully with rituximab. We discuss the role of C1q in this
      clinicopathological entity and question its significance. 

PMID- 25984018
TI  - Acute renal failure after treatment with sunitinib in a patient with multiple
      myeloma.
AB  - Sunitinib is a multiple tyrosine kinase receptors inhibitor that is approved for
      the treatment of advanced renal cell carcinoma. Amongst its targets are fetal
      liver tyrosine kinase receptor 3 (FLT 3) and vascular endothelial growth factor
      receptor (VEGFR). Renal toxicity has not been reported from the trials, but
      several patients have been reported to develop a pre-eclampsia-like syndrome. We
      report the first case of acute tubular necrosis in a patient with multiple
      myeloma following treatment with sunitinib. 

PMID- 25984019
TI  - Olmesartan medoxomil-induced acute renal failure in a premature newborn following
      maternal exposure during pregnancy: a case report and review of the literature.
AB  - Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (AT II)
      receptor blockers (ARBs) are widely used antihypertensives with well-recognized
      renoprotective and cardioprotective effects. Although treatment with these agents
      generally does not result in adverse metabolic consequences, their use during
      human pregnancy has been associated with negative reactions. Here we report a
      premature baby with a history of oligohydramnios and maternal exposure to the ARB
      olmesartan medoxomil who was transferred to our institution with acute renal
      failure. Conservative treatment with diuretics and meticulous management of
      fluids and electrolytes resulted in an improvement in renal function in the
      patient. We conclude that olmesartan medoxomil may cause reversible renal failure
      in premature neonates. 

PMID- 25984020
TI  - Acetazolamide may provoke cyclosporine toxicity-a case report.
AB  - We describe a 58-year-old female renal transplantant recipient with standard
      cyclosporine-based immunosuppression who developed a potentially toxic
      cyclosporine concentration of 265 ng/ml after having started acetazolamide for
      severe glaucoma. The mechanism explaining the interaction between acetazolamide
      and cyclosporine remains unknown, but the concomitant use of these agents is not
      uncommon. The follow-up of cyclosporine concentrations is necessary, and the
      reduction of the cyclosporine dose is likely to be needed when patients taking
      cyclosporine are started with acetazolamide. 

PMID- 25984021
TI  - Anti-CTLA-4 (CD 152) monoclonal antibody-induced autoimmune interstitial
      nephritis.
AB  - Targeted immune-modulating agents are entering clinical practice in many
      specialties, providing novel therapeutic possibilities but introducing new
      potential toxicities. We present the first reported case, to our knowledge, of
      immune-mediated nephritis following the administration of Tremelimumab (CP-675,
      206), an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal
      antibody. High-dose steroid therapy led to a rapid improvement in renal function,
      avoiding the need for renal replacement therapy. 

PMID- 25984022
TI  - Aeromonas hydrophila sepsis with septic embolism and rhabdomyolysis in a chronic
      iron overload haemodialysis patient treated with deferoxamine.
AB  - Aeromonas infection in humans is associated with certain underlying diseases,
      especially chronic liver disease or malignancy. However, Aeromonas infection
      associated with iron overload is rarely reported. We report a case of a 47-year
      old female with end-stage renal disease on haemodialysis and on deferoxamine
      treatment for iron overload who developed Aeromonas sepsis with septic embolism
      and rhabdomyolysis. Although the patients with Aeromonas infection and
      rhabdomyolysis have been correlated with high mortality, this reported case
      survived. We suggest that a chronic haemodialysis patient on deferoxamine
      treatment for iron overload is vulnerable to Aeromonas infection. In such cases,
      the clinician should be alerted to the possibility of rhabdomyolsis, and frequent
      haemodialysis is necessary. 

PMID- 25984023
TI  - Membranous nephropathy associated with gastrointestinal stromal tumour: a case
      report.
AB  - Membranous nephropathy (MN) is a common cause of nephrotic syndrome in older
      adults. The association of MN with neoplasia has been controversial, but several
      recent studies have shown increase incidence of cancer in patients with MN [1].
      We report a case of a 49-year-old male with severe nephrotic syndrome and
      concomitant jejunal gastrointestinal stromal tumour (GIST). The combination of
      preoperative Imatinib mesylate chemotherapy and tumour excision was followed by
      complete resolution of proteinuria within 19 months, without specific treatment
      for MN. An association between MN and GIST has never previously been reported in
      the literature. 

PMID- 25984024
TI  - Chelation of gadolinium with deferoxamine in a patient with nephrogenic systemic
      fibrosis.
AB  - A 65-year-old female with biopsy-confirmed nephrogenic systemic fibrosis (NSF)
      received a kidney transplantation. Despite good kidney function, her symptoms
      continued to progress. Deferoxamine was administered intramuscularly at 500
      mg/day and later 1000 mg/day after 1 week with no adverse effects. Urine
      excretion of gadolinium increased from 6.0 MUg/day to 11.6 MUg/day and
      subsequently to 13.0 MUg/day with 500 mg/day and 1000 mg/day of deferoxamine,
      respectively. Serum levels, however, remain unchanged from 1.7 ng/ml to 1.4
      ng/ml. Although chelation therapy may have a role in the treatment of NSF,
      deferoxamine is too weak and a stronger chelator is needed. 

PMID- 25984025
TI  - Partial nephrectomy for renal cell carcinoma in an allograft kidney with limited
      functional reserve.
AB  - The increased risk of malignancies is a well-recognized complication of organ
      transplantation. When renal cell carcinoma (RCC) occurs in kidney transplant
      recipients, less than 10% of it affects the allograft. Recent experience suggests
      that partial allograft nephrectomy for tumours less than 4 cm may be considered
      the treatment of choice. We report a case of a 3.3 cm RCC discovered in a renal
      allograft. Limited allograft function was due to segmental infarction after
      transplant surgery and chronic allograft nephropathy. She underwent successful
      partial allograft nephrectomy. At 36 months post-surgery, there is no evidence of
      RCC recurrence and she remains free of renal replacement therapy. 

PMID- 25984026
TI  - Chronic hypokalaemia and nephrocalcinosis.

PMID- 25984027
TI  - Arteriovenous malformation in a kidney allograft.

PMID- 25984028
TI  - Renal failure, mental retardation and eponymous confusion.

PMID- 25984029
TI  - An incidental finding while investigating secondary hypertension: severe
      abdominal aortic pseudocoarctation.

PMID- 25984030
TI  - A renal transplant recipient with intraglomerular Candida albicans.

PMID- 25984032
TI  - Mutations in the RARE and MARE regulatory sequences of HNF1beta are not a
      frequent cause of kidney/urinary tract malformation.

PMID- 25984031
TI  - Transient blindness and seizures in severe lupus nephritis.

PMID- 25984033
TI  - Conductivity pulses needed for Diascan(r) measurements: does it cause sodium
      burden?

PMID- 25984034
TI  - Assessment and reduction of fluid overload using a body composition monitor.

PMID- 25984036
TI  - A case of adult atypical haemolytic uraemic syndrome related to anti-factor H
      autoantibodies successfully treated by plasma exchange, corticosteroids and
      rituximab.
AB  - Complement factor H auto-antibodies (CFH-ab) are a rare cause (6-10%) of atypical
      haemolytic uraemic syndrome (aHUS). All observations previously described were
      retrospective and occurred in children or teenagers. We report the first case of
      aHUS associated with anti-CFH antibodies in an adult patient who was successfully
      treated by plasma exchange, corticosteroids and rituximab. 

PMID- 25984037
TI  - Improvement of cardiac function after kidney transplantation with dilated
      cardiomyopathy and long dialysis vintage.
AB  - Patients with long dialysis vintage have low cardiac output for various reasons.
      Although kidney transplantation is known to improve cardiac mortality, patients
      are sometimes evaluated as contraindicated for transplantation because of cardiac
      risk. We successfully performed kidney transplantation for a patient with a long
      dialysis vintage and dilated cardiomyopathy. Sequential (123)I
      metaiodobenzylguanidine ((123)I-MIBG) scintigraphy suggested that amelioration of
      uraemia improved cardiac function. Kidney transplantation for patients with
      severely impaired cardiac function is safe and effective under careful
      perioperative monitoring irrespective of dialysis vintage. Sequential (123)I-MIBG
      scintigraphy can be used as an evaluation tool for the improvement in cardiac
      function. 

PMID- 25984038
TI  - Metastatic pulmonary calcification in a patient with long dialysis vintage.

PMID- 25984039
TI  - H1N1 infection and acute kidney injury in the critically ill.

PMID- 25984040
TI  - Successful cinacalcet treatment of refractory secondary hyperparathyroidism due
      to multiple lung parathyroid adenomas.
AB  - We describe a 56-year-old woman who presented with end-stage renal disease due to
      pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had
      started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However,
      intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she
      underwent a second PTx. However, therapy failed to significantly decrease iPTH
      levels. A third PTx was performed, but no pathological parathyroid tissue was
      found. Computed tomography scan indicated the presence of multiple ectopic lung
      nodules and 26 nodules were surgically removed from the left lung. Despite
      surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to
      decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the
      cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout
      the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone
      alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually
      disappeared. Bone mineral density (BMD) was improved by administration of
      cinacalcet. In conclusion, cinacalcet was effective in this patient with
      refractory and inoperable sHPT. In addition, it improves their BMD and relieves
      bone pain. 

PMID- 25984041
TI  - Treat the patient not the lab value.

PMID- 25984042
TI  - Peritubular capillary lesions in post-streptococcal acute glomerulonephritis.

PMID- 25984043
TI  - Mycotic aneurysm of the carotid artery in a chronic haemodialysis patient.

PMID- 25984044
TI  - Membranous glomerulonephritis secondary to Borrelia burgdorferi infection
      presenting as nephrotic syndrome.

PMID- 25984046
TI  - Adenine phosphoribosyltransferase (APRT) deficiency: a new genetic mutation with
      early recurrent renal stone disease in kidney transplantation.
AB  - Adenine phosphoribosyltransferase (APRT) deficiency, a rare inborn error
      inherited as an autosomic recessive trait, presents with 2,8-dihydroxyadenine
      (2,8-DHA) crystal nephropathy. We describe clinical, biochemical and molecular
      findings in a renal transplant recipient with renal failure, 2,8-DHA stones and
      no measurable erythrocyte APRT activity. Homozygous C > G substitution at -3 in
      the splicing site of exon 2 (IVS2 -3 c > g) was found in the APRT gene. The
      patient's asymptomatic brother was heterozygous for such mutation, and his APRT
      activity was 23% of controls. A splicing alteration leading to incorrect gene
      transcription and virtually absent APRT activity is seemingly associated with the
      newly identified mutation. 

PMID- 25984045
TI  - 'Reality and desire' in the care of advanced chronic kidney disease.
AB  - There is a long distance between the actual worldwide reality in advanced chronic
      kidney disease care and the desire of how these patients should be managed to
      decrease cardiovascular and general morbidity and mortality. Implementation of
      adequate infrastructures may improve clinical outcomes and increase the use of
      home renal replacement therapies (RRT). Current pitfalls should be addressed to
      optimise care: inadequate medical training for nephrological referral and RRT
      selection, late referral to nephrologists, inadequate patient education for
      choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics
      and lack of programmed RRT initiation. These deficiencies generate unintended
      consequences, such as inequality of care and limitations in patient education and
      selection-choice for RRT technique with limited use of peritoneal dialysis.
      Multidisciplinary advanced kidney disease clinics may have a direct impact on
      patient survival, morbidity and quality of life. There is a common need to reduce
      health care costs and scenarios increasing PD incidence show better efficiency.
      The following proposals may help to improve the current situation: defining the
      scope of the problem, disseminating guidelines with specific targets and quality
      indicators, optimising medical speciality training, providing adequate patient
      education, specially through the use of general decision making tools that will
      allow patients to choose the best possible RRT in accordance with their values,
      preferences and medical advice, increasing planned dialysis starts and involving
      all stakeholders in the process. 

PMID- 25984047
TI  - An expanded syndrome of dRTA with hearing loss, hyperoxaluria and beta2
      microglobulinuria.
AB  - We describe a 7-month-old male with atypical features of autosomal recessive
      distal renal tubular acidosis (dRTA) with sensorineural hearing loss.
      Uncharacteristically, he presented with mild acidosis, hypokalaemia and
      hypocalciuria as well as unilateral sensorineural hearing loss. Subsequent
      investigations led to the discovery of both hyperoxaluria and beta2
      microglobulinuria, thereby expanding the differential diagnosis to include both
      primary hyperoxaluria and Dent disease. Two mutations in the ATPV1B1 gene, one of
      which was novel, confirmed the diagnosis of dRTA. We consider the overlapping
      features of and diagnostic dilemmas involved in making a diagnosis of dRTA,
      primary hyperoxaluria and Dent disease in patients with infantile
      nephrocalcinosis. We highlight the occurrence of hyperoxaluria and low-molecular
      weight proteinuria in patients with dRTA and propose that the phenotype of
      autosomal recessive dRTA with sensorineural hearing loss be broadened to include
      both hyperoxaluria and increased urinary excretion of beta2-microglobulin. 

PMID- 25984048
TI  - Coincidental finding of Fabry's disease in a patient with IgA nephropathy.
AB  - We present the case of a woman with IgA nephropathy and concomitant Fabry's
      disease. She was referred to our hospital with proteinuria and haematuria. A
      renal biopsy showed findings indicating IgA nephropathy under light and
      immunofluorescence microscopy. Electron microscopy, however, showed laminated
      inclusion bodies characteristic of Fabry's disease. The alpha-galactosidase
      activity in her serum was low, and the diagnosis of Fabry's disease was confirmed
      by genetic analysis. Fabry's disease in a patient with IgA nephropathy is a very
      rare occurrence, and Fabry's disease diagnosed only by electron microscopy has
      not been previously reported. 

PMID- 25984049
TI  - Haemolytic uraemic syndrome associated with H1N1 influenza.
AB  - Haemolytic uraemic syndrome (HUS) is one of the two forms of thrombotic
      microangiopathies and is characterized by the triad of microangiopathic
      haemolytic anaemia, thrombocytopaenia, and acute renal failure. It has been
      associated with bacterial and viral infections as well as non-infective causes.
      We report a subject who presented with HUS associated with an influenza-like
      syndrome which was confirmed as an influenza A (H1N1) infection. There are
      reports of HUS associated with seasonal influenza, but there have been no
      reported cases of HUS after novel influenza A (H1N1) in the literature so far. 

PMID- 25984050
TI  - Diffuse alveolar haemorrhage in ANCA-negative pauci-immune crescentic
      glomerulonephritis.
AB  - Pulmonary renal syndrome (PRS) is a combination of diffuse pulmonary haemorrhage
      and glomerulonephritis (GN). Though an established form of presentation in anti
      neutrophil cytoplasmic autoantibody (ANCA)-associated GN and vasculitis, diffuse
      pulmonary haemorrhage is extremely unusual in those with ANCA-negative GN. We
      present here a case of a 76-year-old Hispanic female with stage IV chronic kidney
      disease (serum creatinine of 2 mg/dL), who presented with diffuse alveolar
      haemorrhage and nephritic syndrome. Less than 1 week prior to the full-blown PRS,
      she was treated for an apparent pneumonia as was evidenced by a right lower lobe
      infiltrate on her chest X-ray. Retrospectively, this was likely a focal pulmonary
      haemorrhage. ANCA were persistently negative, and the remainder of her
      immunologic workup was normal. Renal biopsy was diagnostic of crescentic pauci
      immune GN. The patient required a ventilator and haemodialysis support (serum
      creatinine 6 mg/dL), and was successfully treated with methylprednisolone,
      cyclophosphamide and a total of six cycles of plasmapheresis. Once her oliguria
      resolved, the creatinine plateaued at 2.7 mg/dL. Our case illustrates that
      diffuse alveolar haemorrhage can be a distinct clinical feature even in patients
      with ANCA-negative pauci-immune crescentic glomerulonephritis. 

PMID- 25984051
TI  - IgA nephropathy in a patient presenting with scleritis.
AB  - Scleritis is a very uncommon manifestation in patients with IgA nephropathy.
      Here, we report the case of a patient presenting with diffuse anterior scleritis
      in which the laboratory disclosed microscopic haematuria and nephrotic range
      proteinuria. Renal function was normal. Serology for lupus, vasculitis and
      cryoglobulinaemia was negative. Rheumatoid factor was negative, and serum C3 and
      serum C4 were on the normal range. Serology for human immunodeficiency virus
      types 1 and 2, hepatitis B, hepatitis C, syphilis, and Lyme disease was also
      negative. A renal biopsy was performed and revealed IgA nephropathy. Oral
      steroids were then started, and 6 months later, the patient was asymptomatic.
      Scleritis did not recur, and ophthalmologic examination was normal; however,
      proteinuria was still in non-nephrotic range. Renal function still remains
      normal. 

PMID- 25984052
TI  - A case of primary immune deficiency presenting with nephrotic syndrome.
AB  - Common variable immunodeficiency (CVID) is the most common form of severe
      antibody deficiency. The disorder is associated with a broad spectrum of clinical
      manifestations, including infections and chronic lung, gastrointestinal and
      autoimmune diseases. A 29-year-old female patient has had frequent sinopulmonary
      infections and gastroenteritis for the last 20 years and had been given broad
      spectrum antibiotics for treatment. Immunoglobulin (Ig) levels were at
      undetectable levels. Renal biopsy was consistent with AA amyloidosis. She is now
      under follow-up with periodic intravenous Ig treatment without any infection
      during the last 10 months. CVID must be kept in mind in patients with recurrent
      sinopulmonary infections. 

PMID- 25984053
TI  - Case report of ecstasy-induced renal venous thrombosis.
AB  - The use of 3,4-methylenedioxymethamphetamine, also known as MDMA or ecstasy, has
      been associated with vascular and end-organ damage. This case report describes,
      with histological evidence, the development renal venous thrombosis presenting
      with acute kidney injury following oral ingestion of 3,4
      methylenedioxymethamphetamine (ecstasy). 

PMID- 25984054
TI  - Progressive renal failure in a patient with lung adenocarcinoma.
AB  - We present an interesting case of a young female smoker who was hospitalized for
      shortness of breath and acute renal insufficiency (serum creatinine = 2.8 mg/dL).
      Few weeks prior to admission, she was discovered to have a right lung mass, and a
      biopsy confirmed lung adenocarcinoma. Her work-up revealed an unremarkable
      urinalysis quantitatively and on microscopic analysis. Renal ultrasound
      demonstrated enlarged bilateral unobstructed kidneys, while a nuclear scan showed
      increased activity in both kidneys. Renal biopsy established the diagnosis of
      diffuse metastatic infiltration of both kidneys from primary lung adenocarcinoma.
      Her renal function worsened despite initiation of chemotherapy. Carcinomatous
      infiltration of the kidneys is an extremely rare and unusual cause of renal
      injury that must be suspected in a patient with cancer and large kidneys. 

PMID- 25984055
TI  - Life-threatening post-thrombectomy hypotension due to residual complications from
      a translumbar catheter.
AB  - Translumbar catheters offer an alternative life-saving option in patients without
      conventional dialysis access, though their use and complication rates are poorly
      understood. We report the first case in the medical literature of a translumbar
      catheter inducing a central venous stenosis. This occult sequela converted what
      is usually a subclinical complication from an arteriovenous graft thrombectomy
      into a life-threatening one. This unusual clinical presentation highlights the
      need for clinicians to recognize the potential serious implications of
      translumbar catheter-induced occult central venous stenosis. 

PMID- 25984056
TI  - A case of CMV infection and encapsulating peritoneal sclerosis in a renal
      transplant recipient.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of
      peritoneal dialysis. It has been reported that the condition of patients with EPS
      may improve after renal transplantation. However, there are also several reports
      of EPS occurring after renal transplantation. In this report, we present a
      patient who developed EPS combined with gastrointestinal cytomegalovirus
      infection 21 months after successful renal transplantation, despite the use of
      tacrolimus and low-dose steroid as maintenance immunosuppression. 

PMID- 25984057
TI  - Peritoneal dialysis (PD) is a successful treatment after complete haemodialysis
      (HD) blood access failure complicated with superior vena cava syndrome (SVCS).
AB  - SVCS constitutes a serious clinical problem and often represents a definitive
      loss of vascular access for haemodialysis (HD). The patients must suffer numerous
      interventions in order to obtain a permanent vascular access for HD. Treatment of
      SVCS requires endovascular intervention or complex surgical revascularization. We
      present three patients with SVCS associated with central indwelling catheters for
      HD who were switched to peritoneal dialysis (PD) due to complete HD blood access
      failure, and discuss the evolution on PD. 

PMID- 25984058
TI  - Pseudo-azotaemia due to intraperitoneal urine leakage: a report of two cases.
AB  - Ascites, oliguria and increasing serum creatinine levels are often noted in
      patients with acute kidney injury. However, these presentations are also observed
      in patients with intraperitoneal urinary leakage. Bladder perforation without
      obvious trauma is sometimes mistaken for acute kidney injury. We report two cases
      of bladder perforation resembling acute kidney injury. The first case was a 37
      year-old woman with delayed intraperitoneal urinary leakage following total
      abdominal hysterectomy, and the second was a 70-year-old woman with spontaneous
      bladder perforation. Although the initial diagnosis in both cases was acute
      kidney injury, rupture of the urinary bladder was later identified. 

PMID- 25984059
TI  - Successful outcome with early renal transplantation following treatment of
      encapsulating peritoneal sclerosis.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal
      dialysis (PD) associated with cocooning of the bowel within a sheath of fibrous
      tissue causing obstruction. Uncertainty remains regarding the aetiology,
      pathogenesis and optimal treatment. The current management of EPS is largely
      based on case reports and small series, and there are limited data regarding
      outcomes of patients who have undergone renal transplantation following treatment
      for EPS. We present the case of a 28-year-old man with EPS who was treated
      surgically followed by anti-fibrotic therapy, with tamoxifen, and 7 months later
      proceeded to renal transplantation with good outcome. 

PMID- 25984060
TI  - Late presentation of toxoplasmosis in renal transplant recipients.
AB  - Toxoplasma gondii is a rare cause of infection in renal transplant recipients and
      usually occurs within 3 months of transplantation, this being the period of
      maximum immunosuppression. We report two cases of toxoplasmosis presenting
      several years after transplantation. One patient developed Toxoplasma retinitis 4
      years after renal transplantation and lost peripheral vision in his affected eye.
      Another developed cerebral toxoplasmosis 6 years following his second renal
      transplant but did not survive despite treatment. These cases highlight the need
      for a high index of suspicion of toxoplasmosis as a potential diagnosis even
      during the later stages of the post-transplant period as survival is poor without
      early recognition and treatment. 

PMID- 25984061
TI  - Rescue of renal function in a 3-year-old girl with Goodpasture's syndrome with a
      brief review of literature.
AB  - Goodpasture's syndrome has been documented in only a handful of children under
      the age of four. We describe a 3-year-old girl presenting with anaemia and renal
      failure whose kidney biopsy showed anti-glomerular basement membrane (GBM)
      disease. She was treated aggressively with pulse steroids, plasmapheresis and
      monthly infusions of cyclophosphamide. After months of aggressive
      immunosuppression, her renal function normalized, and her anti-GBM antibody
      disappeared. A year after the onset, she underwent a second kidney biopsy for
      persistent proteinuria and hypertension that surprisingly showed focal sclerosing
      glomerulonephritis, an unreported finding at this age. The biopsy showed
      deposition of antibody on the GBM despite the fact that anti-GBM antibody had
      normalized in the serum 5 months earlier. Mycophenolate mofetil was added to the
      immunosuppression at that point. At her 3-year follow-up, creatinine clearance
      was 88.4 mL/min/1.73 m(2), proteinuria was 408 mg/day and blood pressure was
      controlled with enalapril 0.2 mg/kg/day. She has not had a relapse or abnormal
      anti-GBM antibody for 30 months, but her renal prognosis remains guarded. To our
      knowledge, this is the youngest patient to have a successful rescue of renal
      function after isolated Goodpasture's syndrome. 

PMID- 25984062
TI  - Renal allograft function not impacted by extensive aortic dissection.

PMID- 25984063
TI  - Dramatic event after acute ischaemic steal syndrome following arm arteriovenous
      fistulae.

PMID- 25984064
TI  - Positron emission tomography: a precious tool in the challenge of the infected
      cysts in ADPKD.

PMID- 25984065
TI  - Glomeruloid haemangiomas associated with generalized oedema in a patient with
      atypical POEMS syndrome.

PMID- 25984066
TI  - A giant stratified lamellate stone occupying almost the entire urinary bladder.

PMID- 25984067
TI  - Not so simple renal cysts.

PMID- 25984068
TI  - Comments on the case report reported by Elmholdt et al.

PMID- 25984069
TI  - Reply.

PMID- 25984070
TI  - Twinkling sign?

PMID- 25984071
TI  - Reply.

PMID- 25984072
TI  - Nephrogenic systemic fibrosis (NSF): the role of tamoxifen.

PMID- 25984073
TI  - Intussusception of the small bowel in an adult associated with nephrotic
      syndrome.

PMID- 25984074
TI  - Obstructive uropathy due to inflammatory abdominal aortic aneurysm occurring 18
      years after surgical repair of an atherosclerotic aneurysm.

PMID- 25984075
TI  - Validity of haemoglobin A1c and glycoalbumin for an appropriate evaluation of
      glycaemic control in Japanese diabetic patients with chronic renal failure.

PMID- 25984076
TI  - The acute flank pain syndrome: a common presentation of acute renal failure in
      young males in Iceland.

PMID- 25984077
TI  - Lack of MRI neurohypophyseal bright signal in a child with congenital nephrogenic
      diabetes insipidus.

PMID- 25984078
TI  - An unexpected knock on Corrigan's secret door.
AB  - Corrigan's secret door describes a metaphorical escape route for busy physicians.
      The term was derived from the successful and exceptionally busy professional life
      of Irish physician Dominic John Corrigan (1802-80). It is claimed that Corrigan's
      outpatient clinic was so busy that he required a secret door in his consulting
      rooms to escape from the ever-growing queue of eager patients. The origins of
      this charming story are unknown, and the door may have never existed. However, at
      present, Corrigan's secret door is often quoted when busy physicians have their
      own little ways in surviving a stressful professional life. Generations of
      British-trained doctors have grown up with Corrigan's secret door, as it was
      featured in the introduction of the Oxford Handbook of Clinical Medicine.
      Accordingly, trainees as well as more senior doctors are often reminded that
      having a 'secret door' is vital in surviving in the medical profession. My own
      escape is through classical music and the violoncello, in particular. As the name
      implies, my own secret door is normally invisible to colleagues and patients.
      This little article is about a patient who found me out, and a reflection on the
      role of classical music and the cello in my professional life. 

PMID- 25984079
TI  - Saturday, june 26, 2010: poster session 1.

PMID- 25984080
TI  - Sunday, june 27, 2010: free communications.

PMID- 25984081
TI  - Saturday, june 26, 2010: free communications.

PMID- 25984082
TI  - Sunday, june 27, 2010: poster session 2.

PMID- 25984083
TI  - Monday, june 28, 2010: free communications.

PMID- 25984086
TI  - Paper selection committee.

PMID- 25984087
TI  - Welcome address.

PMID- 25984088
TI  - Awards and grants.

PMID- 25984089
TI  - Scientific programme.

PMID- 25984090
TI  - Next Congresses of the ERA-EDTA.

PMID- 25984092
TI  - Novel mutation in Wilms' tumour 1 gene associated with steroid-resistant
      nephrotic syndrome.
AB  - We report the case of a paediatric patient with steroid-resistant nephrotic
      syndrome due to a novel dominant Wilms' tumour 1 mutation. The nucleotide change
      C1184A, identified in exon 9, results in amino acid substitution Ser395Tyr.
      Genotyping of parents and healthy controls indicated that this is a de novo
      mutation not present in healthy individuals. The affected amino acid is
      evolutionarily conserved and is located in a functionally important domain of the
      protein involved in DNA binding. Molecular modelling based on crystallography
      data indicated that the substitution would have a deleterious effect on the
      protein function. 

PMID- 25984091
TI  - Three cases of late-onset oligomeganephronia.
AB  - Oligomeganephronia is classified as a subgroup of renal hypoplasia, characterized
      by histopathologic abnormalities which progress to end-stage renal disease (ESRD)
      by school age. We describe three adult cases of oligomeganephronia who have not
      yet developed ESRD. We performed a renal biopsy in all of them. The pathological
      features, consisting of a reduced number of enlarged glomeruli, were diagnostic
      of oligomeganephronia. It was assumed that the condition had not progressed to
      ESRD in the patients because the degree of loss of glomeruli may have been milder
      than that in typical cases of oligomeganephronia. 

PMID- 25984093
TI  - Minimal change disease: a variant of lupus nephritis.
AB  - Some patients with systemic lupus erythematosus (SLE) present with nephrotic
      syndrome due to minimal change disease (MCD). Histopathological diagnosis of
      patients with SLE and nephrotic-range proteinuria has shown that these patients
      present with diffuse proliferative glomerulonephritis and membranous
      glomerulonephritis, World Health Organization (WHO) classes IV and V,
      respectively, more frequently than the other classes. In the present study, we
      reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with
      SLE. A complete remission occurred after steroid treatment, which was followed by
      a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy
      showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the
      patient went into complete remission again. The association of MCD and SLE may
      not be a coincidence, and MCD should be considered as an associated SLE
      nephropathy. 

PMID- 25984094
TI  - The effects of the recommended dose of creatine monohydrate on kidney function.
AB  - We report a case of a heretofore healthy 18-year-old man who presented with a 2
      day history of nausea, vomiting and stomach ache while taking creatine
      monohydrate for bodybuilding purposes. The patient had acute renal failure, and a
      renal biopsy was performed to determine the cause of increased creatinine and
      proteinuria. The biopsy showed acute tubular necrosis. In the literature,
      creatine monohydrate supplementation and acute tubular necrosis coexistence had
      not been reported previously. Twenty-five days after stopping the creatine
      supplements, the patient recovered fully. Even recommended doses of creatine
      monohydrate supplementation may cause kidney damage; therefore, anybody using
      this supplement should be warned about this possible side effect, and their renal
      functions should be monitored regularly. 

PMID- 25984095
TI  - An elderly 'kawara' craftsman with acute kidney injury and haemoptysis: a case of
      silica-induced autoimmunity.
AB  - A 62-year-old Japanese 'kawara' (ceramic roof tile) craftsman presented with
      acute kidney injury and haemoptysis. This case met the systemic lupus
      erythematosus and microscopic polyangiitis criteria, with high titres of
      myeloperoxidase-antineutrophil cytoplasmic antibody (570 EU). Results showed the
      presence of antinuclear antibody at a high titre (1:2560), but detection of
      rheumatoid factor, anti-dsDNA, anti-SSA and anti-SSB antibodies was not apparent.
      This serology was similar to drug-induced, silicon-induced or silica-induced
      autoimmunity. The patient had been exposed to silica for > 40 years. The
      environmental aetiology of autoimmune diseases should be considered in cases that
      show atypical epidemiology and serology. 

PMID- 25984096
TI  - Progressive renal insufficiency, hypercalcaemia, bicytopaenia and a history of
      breast cancer.
AB  - Sarcoidosis can affect all organs and may mimic a variety of other diseases. In
      the absence of typical pulmonary features, extrapulmonary manifestations may be
      difficult to diagnose. We describe here the very uncommon case of a patient with
      mild pulmonal involvement but distinct renal, bone marrow and lymph node
      sarcoidosis. Treatment with glucocorticoids significantly improved kidney
      function and normalized serum calcium levels as well as the blood count. This
      case underscores the importance of sarcoidosis to be considered as a differential
      diagnosis of renal failure associated with hypercalcaemia and nephrocalcinosis.
      Bone marrow involvement should always be suspected if mono-, bi- or pancytopaenia
      coexist. 

PMID- 25984097
TI  - A case of hepatitis C virus transmission acquired through sharing a haemodialysis
      machine.
AB  - Hepatitis C virus (HCV) infection is a significant problem among haemodialysis
      populations worldwide. 'Horizontal' cross-infection between patients can occur,
      predominately through direct environmental transmission of the virus. Current
      guidelines thus recommend universal barrier precautions, however they do not
      suggest using dedicated machines for HCV-positive patients to prevent the
      'sequential' transmission of virus to those who subsequently use that machine. We
      report a case where sequential HCV transmission occurred from a patient of low
      HCV infectivity with no identifiable machine fault. We suggest that current
      guidelines should be reviewed to encourage the use of dedicated haemodialysis
      machines for HCV-positive patients. 

PMID- 25984098
TI  - Hypoglycaemic coma due to adrenal failure in a chronic haemodialysis patient.
AB  - A 62-year-old man, receiving chronic haemodialysis and suffering from alcoholic
      liver cirrhosis and chronic pancreatitis, presented with hypoglycaemic coma.
      Plasma cortisol was undetectable (< 5.5 nmol/L) with suppressed
      adrenocorticotropic hormone (ACTH), which established a diagnosis of adrenal
      failure due to ACTH deficiency. Twenty-five milligrams of oral hydrocortisone
      eradicated hypoglycaemia. Presentation of adrenal failure in this patient was
      atypical because he was hypertensive, serum electrolytes including sodium were
      normal and anaemia was unremarkable, which were all due to end-stage renal
      disease and its treatment with haemodialysis. As far as we are aware, this is the
      first case report of hypoglycaemic coma due to adrenal failure in a chronic
      haemodialysis patient. 

PMID- 25984099
TI  - A case of pulmonary dialysis-related amyloidosis with reticular opacity of the
      lung in a patient undergoing long-term dialysis.
AB  - Dialysis-related amyloidosis (DRA) is one of the most important complications in
      long-term dialysis patients. Pulmonary involvement in patients with DRA has been
      rarely described, and lung radiographic findings have not yet been reported. The
      most common chronic lung disease process in chronic dialysis patients is
      interstitial fibrosis. This is the first case report of DRA presenting in the
      lung in a manner resembling interstitial pneumonia. This case study suggests that
      interstitial pneumonia as a result of DRA should be considered when dyspnoea and
      reticular opacity of the lung are observed in patients undergoing long-term
      dialysis. 

PMID- 25984100
TI  - Beta HCG levels in a pregnant dialysis patient: a cautionary tale.
AB  - Conception is rare in patients on chronic dialysis and diagnosis is often delayed
      as it is least expected. Serum beta HCG levels are elevated in both pregnant and
      non-pregnant dialysis patients, and pregnant dialysis patients have slightly
      higher beta HCG levels when compared with normal pregnancy. This can be
      erroneously interpreted as non-viable pregnancy and so results should be viewed
      with caution. Serial beta HCG levels must be followed when non-viable pregnancy
      is suspected in a dialysis patient before contemplating termination of pregnancy
      as described in our case. 

PMID- 25984101
TI  - Ranolazine can markedly increase tacrolimus blood levels.
AB  - We report the case of a renal transplant patient on tacrolimus who developed a
      fully reversible renal failure and a doubling in serum tacrolimus closely
      associated with initiation of ranolazine (Ranexa) treatment, a new anti-angina
      drug recently introduced in Europe. 

PMID- 25984102
TI  - Progressive renal failure due to renal infiltration by BK polyomavirus and
      leukaemic cells: which is the culprit?
AB  - Renal infiltration with leukaemic cells is a common finding in patients suffering
      with chronic lymphocytic leukaemia (CLL) but rarely does it lead to significant
      renal dysfunction. Similarly, BK nephropathy is a recognized cause of graft
      failure in renal transplant recipients but rarely causes significant disease in
      native kidneys. In the few reports where leukaemic infiltration of the kidney has
      led to significant renal impairment, the pathological process causing renal
      dysfunction is not identified on biopsy. In these cases, it is unclear whether BK
      polyomavirus (BKV) nephropathy has been excluded. We describe a case of dual
      pathologies in a patient with Binet stage C CLL and deteriorating renal function
      where renal biopsy reveals leukaemic infiltration of the kidney occurring
      alongside BKV nephropathy. The relative importance of each pathology in relation
      to the rapid decline to end-stage renal failure remains unclear, but the presence
      of both pathologies appears to impart a poor prognosis. Additionally, we describe
      the novel histological finding of loss of tubular integrity resulting in tubular
      infiltration and occlusion by leukaemic cells. It is possible that the patient
      with advanced CLL is at particular risk of BK activation, and the presence of BK
      nephropathy may compromise tubular integrity allowing leukaemic cell infiltration
      and obstruction of tubules. This case bares remarkable resemblance to the first
      and only other report of its kind in the literature. It is not clear how
      available immunocytochemistry for polyoma infection is outside transplant
      centres, and it is possible that BK nephropathy is being under-diagnosed in
      patients with CLL in the context of declining renal function. At present, the
      combination of BKV nephropathy and leukaemic infiltration represents a management
      conundrum and the prognosis is poor. Further research is required in order to
      better understand the pathological process and therefore develop management
      strategies. 

PMID- 25984103
TI  - Epstein-Barr virus-associated gastric carcinoma 33 years after kidney
      transplantation.
AB  - Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a unique type of
      gastric cancer, defined as the presence of EBV in gastric tumour cells, usually
      identified by in situ hybridization. A poorly differentiated gastric
      adenocarcinoma was detected in a kidney recipient 33 years after transplantation.
      Neoplastic epithelial cells were EBV positive by in situ hybridization. Gene
      sequencing confirmed the amplicon specificity, and real-time polymerase chain
      reaction quantified 2 600 000 genomes/MUL DNA in neoplastic tissue. No cases of
      EBVaGC have been reported in solid organ transplants, thus this is the first case
      of de novo EBVaGC arising in a 65-year-old renal transplant recipient. 

PMID- 25984104
TI  - Can skin be the first site of CMV involvement preceding a systematic infection in
      a renal transplant recipient?
AB  - Cytomegalovirus (CMV) is an important and well-described opportunistic virus in
      renal transplant recipients (RTRs) with infection occurring mainly after the
      first month post-renal transplant. CMV can present as primary infection,
      reinfection or reactivation of latent disease. Skin manifestations are rare and
      variable, and diagnosis is often delayed. We present one case of skin CMV ulcer
      of perineal areas without systemic symptoms of CMV disease and a negative
      quantitative polymerase chain reaction. This case serves to illustrate the
      protean nature of CMV disease in RTR. 

PMID- 25984105
TI  - Spontaneous bilateral kidney rupture during autologous stem cell transplantation
      in a patient affected by amyloidosis.
AB  - Kidney spontaneous rupture is not a recognized complication neither for
      amyloidosis nor of autologous stem cell transplantation (ASCT). A 46-year-old
      white woman, affected by nephrotic syndrome, was diagnosed as AL amyloidosis by
      renal biopsy. We report the singular case of a bilateral spontaneous kidney
      rupture during ASCT for AL with renal rescue. 

PMID- 25984106
TI  - Nephrotic syndrome in Kimura's disease: apropos a case of the glomerular tip
      lesion in an African-Caribbean male.

PMID- 25984107
TI  - Calcineurin inhibitor-induced pain syndrome after kidney transplantation-a rare
      but disabling condition.

PMID- 25984108
TI  - Nephrotic syndrome and hepatitis due to acquired syphilis: an uncommon
      presentation of a re-emerging disease.

PMID- 25984109
TI  - Acute abdominal pain and chills in an ADPKD transplant recipient.

PMID- 25984110
TI  - Non-hereditary multiple renal cysts in unilateral kidney.

PMID- 25984111
TI  - 'Soybean sauce' peritoneal dialysate.

PMID- 25984112
TI  - Injury, failure or success? Renin-angiotensin system inhibition in acute kidney
      injury.

PMID- 25984113
TI  - Unlikely association of nephrectomy post-mRCC with anti-VEGF-induced renal TMA.

PMID- 25984114
TI  - Haemorrhagic shock induced by subcutaneous insulin injection.

PMID- 25984115
TI  - Renal thrombotic microangiopathy induced by beta-interferon.

PMID- 25984116
TI  - Membranous glomerulonephritis with superimposed ANCA-associated vasculitis:
      another case report.

PMID- 25984117
TI  - Coagulase-negative staphylococcus-oftentimes a virulent masquerader.

PMID- 25984118
TI  - Creatinine determination according to Jaffe-what does it stand for?
AB  - In 1886, Max Jaffe discovered a reaction of creatinine with picric acid in an
      alkaline environment. Although the manuscript describes the nature of a
      precipitate and does not deal with an analytical assay, Jaffe's landmark paper
      elucidated the basic principles of the creatinine determination method
      (originally developed by Otto Folin), which became immensely popular and has
      easily withstood the test of time. Despite the advent of the enzymatic creatinine
      analysis, the analytical method is still popular due to its simplicity and low
      cost. As there is no standard recipe for the 'Jaffe' method, much methodological
      variation has occurred over time. This lack of methodological standardization
      implies that even in the 21st century, improving the interchangeability of Jaffe
      results is still an issue. 

PMID- 25984119
TI  - High-dose continuous venovenous hemofiltration combined with charcoal
      hemoperfusion for methotrexate removal.

PMID- 25984120
TI  - An unusual case of severe high anion gap metabolic acidosis.
AB  - We present a case of high anion gap metabolic acidosis with an unusual aetiology
      in a 75-year-old lady with hypoglycaemia, encephalopathy and relatively preserved
      renal function. Full toxicology and biochemical analysis suggested that she had
      an inborn error of metabolism, riboflavin-responsive multiple acyl-CoA
      dehydrogenase deficiency that can predispose to severe acidosis in situations
      where calorific intake is reduced. We believe this to be one of the few published
      cases and is remarkable for the presentation in late adulthood in addition to the
      requirement for emergency haemodialysis due to the severity of the metabolic
      disturbance. 

PMID- 25984121
TI  - A case of phenotypic and serological transformation in Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is a systemic vasculitis of small- to medium-sized
      arteries, associated with necrotizing granulomata classically involving the upper
      and lower respiratory tracts and kidneys. It is usually associated with the
      presence of anti-neutrophil cytoplasmic antibodies (ANCA). ANCA-negative WG is
      usually a limited form of the disease that tends to affect organs other than the
      kidneys, often the central nervous system. We describe an unusual case presenting
      with ANCA-positive WG affecting the kidneys and upper airway that, despite
      standard treatment, demonstrated a phenotypic and serological transformation into
      an aggressive ANCA-negative WG affecting the central nervous system. 

PMID- 25984122
TI  - Minimal-change renal disease and Graves' disease: a case report and literature
      review.
AB  - OBJECTIVE: To describe a possible association between Graves' disease and
      nephrotic syndrome secondary to minimal change renal disease and to review the
      literature related to renal diseases in patients with Graves' disease. METHODS:
      The clinical, laboratory, and renal biopsy findings in a patient with Graves'
      disease and minimal change renal disease are discussed. In addition, the
      pertinent English-language literature published from 1966 to 2009, determined by
      means of a MEDLINE search, is reviewed. RESULTS: A 63-year-old man who was
      admitted to the hospital with nephrotic syndrome. Patient had a history of
      Graves' disease for last 2 years with associated ophthalmopathy. He had been
      treated with methimazole and low low-dose steroids (prednisone 5 mg daily).
      Examination revealed generalized oedemaedema and exophthalmoses. Laboratory tests
      showed 6.62 g/day of proteinuria. Antinuclear antibodies, anti-glomerular
      basement membrane antibodies, antineutrophil cytoplasmic antibody (ANCA), serum
      complement levels, cryoglobulin, hepatitis screen and serum and urine protein
      electrophoreses were normal. A kidney biopsy revealed features consistent with
      minimal change disease on light, immunofluorescence, and electron microscopy. The
      patient had an excellent clinical and laboratory response after treatment with
      steroids and near total thyroidectomy. CONCLUSIONS: To the best of our knowledge,
      this is the fourth report of the occurrence of minimal change disease in a
      patient with Graves' disease in the absence of any other immunologic disorder
      known to be associated with minimal change renal disease.

PMID- 25984123
TI  - Idiopathic or iatrogenic membranous glomerulonephritis? A case of spironolactone
      induced membranous glomerulonephritis.
AB  - Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in
      adults in the UK. In most cases, the aetiology remains unknown, although recent
      data suggested a clear mechanism of pathogenesis. In approximately a quarter of
      cases, however, a presumed cause is found, such as systemic lupus nephritis,
      malignancy, hepatitis B and various drugs. Here, we present a patient who
      developed MN soon after commencing spironolactone and whose condition persisted
      for the duration of exposure to the drug only to resolve with cessation of the
      drug. No cases of spironolactone-induced MN have been reported in the literature
      previously. 

PMID- 25984124
TI  - Spontaneous perinephric hematoma due to acquired factor X deficiency in AL
      amyloidosis.
AB  - Spontaneous perinephric hematoma (SPH) is a rare entity whose diagnosis is
      challenging because of its varied clinical presentation and lack of any specific
      etiology. We report a 34-year-old African-American male who presented with left
      flank pain and was found to have a large left perinephric hematoma, in the
      setting of undiagnosed AL amylodosis. The case illustrates that while a SPH due
      to the vascular angiopathy of amyloid is rare, when amyloidosis is associated
      with abnormal coagulation studies or bleeding at multiple sites, it should be
      considered because of its protean systemic manifestations and potential response
      to chemotherapy. 

PMID- 25984125
TI  - AA amyloidosis in a patient with Langerhans cell histiocytosis.
AB  - We report the case of a 37-year-old woman who presented with progressive renal
      dysfunction and proteinuria, in whom renal biopsy confirmed a diagnosis of AA
      amyloidosis. No evidence of chronic suppurative infection, connective tissue
      disease or malignancy was found. A past history of Langerhans cell histiocytosis
      (LCH) diagnosed in childhood was noted for which the patient had been
      successfully treated with surgical excision, corticosteroids, radiotherapy and
      chemotherapy. Renal disease in LCH is not widely recognized and thus we describe
      a patient with LCH in whom AA amyloidosis developed in the absence of any other
      established cause. 

PMID- 25984126
TI  - Encapsulating peritoneal sclerosis following a peritoneal foreign body reaction
      to Dacron fibres-a case report.
AB  - The aetiological factors and the pathophysiological mechanisms of encapsulating
      peritoneal sclerosis (EPS) have not been fully elucidated. We present a patient
      on continuous ambulatory peritoneal dialysis whose peritoneal catheter was
      exchanged due to repeated episodes of bacterial peritonitis. Immediately
      afterwards, he experienced severe abdominal pain, nausea and fever. Peritoneal
      biopsy, taken 12 days after the operation, revealed fibrotic thickening of the
      peritoneum and a foreign body inflammatory reaction to particles manifesting
      striking similarity to the Dacron fibres of the catheter cuff. Shedding of Dacron
      fibres into the peritoneum may have elicited the acute fulminant phase of the EPS
      diagnosed in this case. 

PMID- 25984127
TI  - Hot flushes, hypertension and haemodialysis.
AB  - Hypertension is common in patients with end stage renal disease. However, in
      patients non-responsive to standard measures to control the blood pressure, non
      renal causes should be considered. We present the case of a patient on
      haemodialysis with difficult to control blood pressure. 

PMID- 25984128
TI  - Intra-operative continuous renal replacement therapy during combined liver-kidney
      transplantation in two patients with primary hyperoxaluria type 1.
AB  - Liver-kidney transplantation in patients with primary hyperoxaluria type 1 (PH1)
      and a high systemic oxalate load is often complicated by oxalate deposition in
      the renal allograft and loss of renal function. Intensive pre- and post-operative
      haemodialysis (HD) cannot completely prevent rises in plasma oxalate levels
      during transplantation because of rebound from saturated oxalate stores.
      Continuous renal replacement therapy may overcome this problem. In two PH1
      patients with extensive oxalate accumulation, we found that intra-operative
      continuous venovenous haemodiafiltration effectively cleared oxalate and kept
      oxalate at relatively low levels following preoperative HD. 

PMID- 25984130
TI  - Pneumoperitoneum in peritoneal dialysis patients; one centre's experience.
AB  - The pneumoperitoneum (PP) on upright chest X-ray (CXR) usually indicates a
      perforated viscus. As peritoneal dialysis (PD) catheter provides an additional
      port of air entry into the peritoneal cavity, the incidence and clinical
      significance of PP in PD patients has been debated in the literature (a variable
      incidence from 4 to 34% has been reported in previous studies). With improvement
      in patient training and connecting devices of PD catheters, technique-related PP
      is quite rare. Following a recent patient with PP, we reviewed our 3-year data to
      evaluate the incidence and significance of this radiological sign in PD patients.
      We reviewed all upright CXRs in our PD patients from 2006 to 2008, using an
      electronic radiology database. Over 3 years, we had a total of 156 patients on
      PD. We have reviewed a total 312 upright CXRs (mean 2 X-rays per patient), which
      were performed for various clinical reasons during this period. Seven PD patients
      had 11 CXRs showing free air under the diaphragm (total incidence of PP 4% of PD
      population and 3% of CXR performed in PD patients). One patient had two episodes
      of PP with a total of four X-rays demonstrating free air. Two patients had
      surgical complications of PD catheter insertion and PP was diagnosed just after
      the insertion of PD catheter, both of them needed laparotomy. Five patients had
      incidental PP, which was possibly technique related. In four of these patients
      with incidental PP, no definite intervention was needed. However, one of these
      five patients was symptomatic. We established that the cause of PP was faulty
      technique. Aspiration of PP with a patient in the Trendelenburg position gave her
      immediate symptomatic relief. We also retrained her to prevent further episodes
      of PP. This review demonstrates the quite low and falling incidence of PP (<4% in
      a prevalent PD population) most likely due to improvement in training and
      technique. The air should not enter the peritoneal cavity in normal properly
      performed exchanges. Air under the diaphragm in a PD patient requires appropriate
      evaluation to exclude visceral perforation. After that, patient technique of PD
      exchanges should be reviewed. However, if PP persists, aspiration of air can give
      symptomatic relief. 

PMID- 25984129
TI  - Post-parathyroidectomy thyrotoxicosis and atrial flutter: a case for caution.
AB  - Despite transient hyperthyroidism reportedly occurring in ~30% of post
      parathyroidectomy (PTX) patients with primary hyperparathyroidism, it has rarely
      been described in the internal medicine literature. It occurs within days of
      surgery, is usually clinically mild or silent, and typically spontaneously
      resolves within weeks. Patients can, however, unusually present with symptoms and
      signs of thyrotoxicosis, including arrhythmias. We report a case of a
      hemodialysis patient who developed self-limited hyperthyroidism after intra
      operative thyroid manipulation and excision during PTX surgery for secondary
      hyperparathyroidism that failed medical management. The patient was symptomatic
      with agitation, restlessness and new-onset atrial flutter, which required
      electrical cardioversion and temporary beta blockade. It is important that
      clinicians be aware of this potential surgical complication, so as to not
      attribute manifestations to post-PTX divalent cation disorders (i.e. hungry bone
      syndrome), thereby allowing prompt diagnosis and treatment. Post-operative
      monitoring of thyroid function is warranted for at least some subsets of
      patients: individuals who undergo thyroid exploration and palpation as part of
      their surgery to localize the parathyroid glands, as well as those with
      underlying cardiac disease or who are otherwise at high risk from even mild
      states of hyperthyroidism. 

PMID- 25984131
TI  - An unusual presentation of atrial myxoma with haematuria and proteinuria.
AB  - Myxomas are uncommon primary cardiac tumours, usually affecting the left atrium.
      We describe an unusual presentation of cardiac myxoma with asymptomatic
      proteinuria and haematuria. Surgical excision of the tumour resulted in complete
      resolution of the urinary abnormalities. The production of antiendothelial cell
      antibodies and interleukin-6 by cardiac myxomas may be relevant as these
      substances have been implicated with the development of renal injury and
      proteinuria. 

PMID- 25984132
TI  - A case of bilateral renal masses: dilemmas in their evaluation and management.

PMID- 25984133
TI  - Fever, acute renal failure and pulmonary edema.

PMID- 25984134
TI  - Massive abdominal herniation after dual kidney transplantation.

PMID- 25984135
TI  - Hydropneumonephroureter and emphysematous cystitis.

PMID- 25984136
TI  - A case of shoulder pain post-renal transplant: an unusual etiology.

PMID- 25984137
TI  - Increased tubular creatinine secretion by remnant nephrons-unexplained but
      informative?

PMID- 25984138
TI  - Two cases of pregabalin neurotoxicity in chronic kidney disease patients.

PMID- 25984139
TI  - A neonate with severe oligo-anuric renal failure during multi-organ failure
      survived with prolonged renal replacement therapy.

PMID- 25984140
TI  - Renal tubular dysgenesis and reversible hypocalvaria after intrauterine exposure
      to an angiotensin receptor blocker.

PMID- 25984141
TI  - Coiled catheter for recurrent migration.

PMID- 25984142
TI  - Outcome of patients on haemodialysis in Khuzestan, Iran.

PMID- 25984143
TI  - Reverse PD-a rare cause of acute renal failure in a transplanted patient.

PMID- 25984145
TI  - Military nephrology-what a civilian doctor should know.
AB  - This article provides some background on military nephrology in the UK. The
      primary objective of the Defence Medical Services is the maintenance of
      operational capability of military personnel. This includes exclusion of
      nephrological diseases that might reduce renal reserve to a critical level under
      field conditions, increasing susceptibility to trauma, burns, infection and
      adverse environmental conditions and increasing the need for renal support. Renal
      failure potentially compromises not only the patient but also his comrades
      through reduced staffing and inability to execute the military mission. Safety of
      weapon systems for which the patient is responsible may be reduced. At forward
      locations, need for evacuation may put aircraft or vehicles and their crew with
      medical attendants at unnecessary risk. Regular follow-up and continuity of care
      are difficult owing to the demands of military life that include frequent
      postings and deployments. 

PMID- 25984144
TI  - Renal involvement in leishmaniasis: a review of the literature.
AB  - Leishmaniasis, an infectious disease endemic in tropical, Asian and southern
      European countries, is caused by obligate intramacrophage protozoa and is
      transmitted through the bite of infected female sandflies. More than 20
      leishmanial species are responsible for four main clinical syndromes: cutaneous
      leishmaniasis; mucocutaneous leishmaniasis; visceral leishmaniasis, also known as
      kala-azar, and post-kala-azar dermal leishmaniasis. Visceral leishmaniasis can
      present with varying clinical features and the kidney can also be involved. Both
      glomerular and tubular function can be altered and patients can develop
      proteinuria, haematuria, abnormalities in urinary concentration and acidification
      and acute and chronic renal insufficiency. Not only the disease itself but also
      the therapy administered might be responsible for the renal involvement in kala
      azar. Indeed, some of the agents with efficiency against visceral leishmaniasis,
      such as pentavalent antimonial drugs, amphotericin B, pentamidine, miltefosine,
      paromomycin and simataquine, may be associated with a high risk of renal
      toxicity. In this article, the literature on renal involvement in visceral
      leishmaniasis is reviewed. 

PMID- 25984146
TI  - Case report: a rare cause of metabolic alkalosis.
AB  - A case of a 66-year-old white man with recent onset of oedema, hypertension,
      metabolic alkalosis and profound hypokalaemia is described. The initial
      laboratorial workup showed that urinary chloride concentration and potassium
      excretion were increased, suggesting a state of hyperaldosteronism. Nonetheless,
      renin activity was low and aldosterone levels were normal. The metabolic
      alkalosis seen in this case was due to a rare cause, the ectopic
      adrenocorticotropic hormone syndrome. A literature review in the subject is
      presented. 

PMID- 25984147
TI  - Yellow jacket envenomation-related acute renal failure.
AB  - We report a 58-year-old man with multiple yellow jacket stings who developed
      urticaria, renal failure, quadriparesis, rhabdomyolysis in succession.
      Investigations revealed renal and hepatic dysfunction, proteinuria, demyelinating
      polyradiculoneuropathy, acute tubular necrosis and glomerulonephritis. He
      improved with methylprednisolone, antihypertensives and two sessions of
      haemodialysis. 

PMID- 25984148
TI  - A case of mononucleosis infectiosa presenting with cholemic nephrosis.
AB  - A 38-year-old male was admitted with fever, progressive jaundice, cervical
      lymphadenopathy, hepatomegaly and acute oliguric renal failure. Epstein-Barr
      virus (EBV) infection was diagnosed by detection of EBV-DNA in plasma and
      confirmed by EBV seroconversion. Kidney biopsy revealed acute tubular necrosis
      and abundant casts, consisting of bilirubin pigment. With conservative treatment,
      the patient fully recovered from cholemic nephrosis, an uncommon condition, not
      described after EBV infection before. 

PMID- 25984149
TI  - An unusual case of rhabdomyolysis.
AB  - We report an unusual case of rhabdomyolysis due to coturnism (food poisoning
      caused by eating quails). The patient's clinical course is described, and
      possible pathogenetic mechanisms of this syndrome are briefly discussed. 

PMID- 25984150
TI  - A rare clinical syndrome of refractory secondary hypertension, renal artery
      stenosis and erythrocytosis.
AB  - Clinical syndrome of refractory secondary hypertension, renal artery stenosis and
      secondary erythrocytosis could occur in the same patient. We report a rare case
      of refractory secondary hypertension, renal artery stenosis and primary
      erythrocytosis as an expression of polycythaemia rubra vera (PV) and suggest that
      erythrocytosis in a hypertensive renovascular occlusive disease may be primary
      due to underlying PV. This clinical syndrome should be excluded in such patients
      with refractory hypertension. 

PMID- 25984151
TI  - Rapid and sustained response to tocilizumab, anti-interleukin-6 receptor
      antibody, in a patient with nephrotic syndrome secondary to systemic juvenile
      idiopathic arthritis-related amyloidosis.
AB  - AA amyloidosis, or secondary amyloidosis, is a rare but serious complication of
      chronic inflammatory diseases. Chronic inflammatory arthritis is the commonest
      cause of AA amyloidosis and, when the latter appears, treatment can be
      frustrating. Deposition of fibrils, derived from circulating acute-phase reactant
      serum amyloid A protein (SAA), in the kidneys can lead to proteinuria and
      progressive loss of renal function. We describe the case of a 14-year-old female
      with systemic juvenile idiopathic arthritis who developed nephrotic syndrome
      secondary to AA amyloidosis; while she was unresponsive to all measures,
      including anti-tumour necrosis factor therapy, treatment with tocilizumab, an
      anti-human interleukin-6 receptor antibody, immediately normalized the SAA and
      reversed the nephrotic syndrome. We discuss this new therapeutic approach. 

PMID- 25984152
TI  - IgA-dominant Staphylococcus infection-associated glomerulonephritis: case reports
      and review of the literature.
AB  - Background and objectives. The mesangial deposition of IgA is rarely described
      with proliferative glomerulonephritis associated with Staphylococcus infection.
      Recently, this association has been increasingly recognized possibly due to the
      increased rate of Staphylococcus infection. Design setting, participants and
      measurements. We report two cases of methicillin-sensitive Staphylococcus aureus
      bacteremia associated with acute proliferative glomerulonephritis with dominant
      mesangial deposit of IgA. We searched MEDLINE (1960-2009) for similar reports. We
      pooled individual patient data and reported descriptive statistics of all
      published cases. Results. Forty-six cases were included in the final analysis.
      The mean age of presentation was 59, with a male predominance (84%). Clinical
      presentation was notable for rapidly progressive glomerulonephritis with
      nephrotic-range proteinuria and normal complement levels in 52 and 72%,
      respectively. Methicillin-resistant S. aureus (68%) was the most common pathogen
      isolated with a latent period ranging from 1 to 16 weeks. Diffuse mesangial
      proliferation was commonly found with crescentic lesions noted in 35% of the
      cases. Antimicrobial treatment was associated with renal recovery in 58% of the
      cases. Need for renal replacement therapy was significantly associated with pre
      existing diabetes, hypertension and interstitial fibrosis seen on kidney biopsy.
      Conclusions. IgA-dominant post-Staphylococcus glomerulonephritis is a rare
      clinical entity with certain unique clinical and morphologic features. It is
      difficult to differentiate from primary IgA nephropathy in cases where the
      infection is not apparent. An acute onset of rapidly progressive
      glomerulonephritis, with normal complement levels and deposition of mesangial IgA
      in an elderly patient should raise suspicion for this rare form of
      glomerulonephritis. 

PMID- 25984153
TI  - Successful treatment of non-Hodgkin's lymphoma with rituximab and dose-adjusted
      CHOP therapy in a patient with concomitant end-stage renal disease requiring
      haemodialysis.
AB  - Although malignancy is a fatal complication of end-stage renal disease (ESRD)
      requiring haemodialysis, successful treatment of haematological malignancies has
      been rarely reported. We describe the case of a 64-year-old man who presented
      with non-Hodgkin's lymphoma (NHL; clinical stage, IVB) concomitant with ESRD.
      Before chemotherapy, haemodialysis was initiated, and one course of dose-adjusted
      CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy
      followed by eight courses of rituximab therapy were administered according to the
      performance status and degree of organ dysfunction. Consequently, the patient was
      disease free for 27 months. Thus, rituximab plus CHOP combination therapy was
      effective for NHL concomitant with ESRD. 

PMID- 25984154
TI  - Vaccination and transient hepatitis B surface antigenemia.
AB  - Hepatitis B vaccination is mandatory for all hepatitis B surface antigen (HBsAg)
      negative hemodialysis (HD) patients with low hepatitis B surface antibody titers.
      We report a case of transient hepatitis B surface antigenemia, detected
      incidentally, in an HD patient after the second dose of Hepatitis B vaccine. The
      patient had to be isolated on a separate HD machine, in a separate room, until
      further investigations ruled out a true hepatitis B virus infection. This led to
      further unnecessary testing and generated great concern and anxiety for the
      patient. We present this case to emphasize that HD units should be aware of this
      phenomenon and that HBsAg testing be deferred until 4 weeks after vaccination to
      avoid HBsAg false positivity. 

PMID- 25984155
TI  - Encephalopathy caused by lanthanum carbonate.
AB  - Lanthanum carbonate is a nonaluminum, noncalcium phosphate-binding agent, which
      is widely used in patients with end-stage chronic kidney disease. Until now, no
      significant side-effects have been described for the clinical use of lanthanum
      carbonate, and there are no available clinical data regarding its tissue stores.
      Here we report the case of a 59-year-old patient who was admitted with
      confusional syndrome. The patient received 3750 mg of lanthanum carbonate daily.
      Examinations were carried out, and the etiology of the encephalopathy of the
      patient could not be singled out. The lanthanum carbonate levels in serum and
      cerebrospinal fluid were high, and the syndrome eased after the drug was removed.
      The results of our study confirm that, in our case, the lanthanum carbonate did
      cross the blood-brain barrier (BBB). Although lanthanum carbonate seems a safe
      drug with minimal absorption, this work reveals the problem derived from the
      increase of serum levels of lanthanum carbonate, and the possibility that it may
      cross the BBB. Further research is required on the possible pathologies that
      increase serum levels of lanthanum carbonate, as well as the risks and side
      effects derived from its absorption. 

PMID- 25984156
TI  - Long-term pneumoperitoneum in continuous ambulatory peritoneal dialysis (CAPD)
      caused by handling fault of Stay.Safe(r) system associated to bicaVera solution.
AB  - We found chronic pneumoperitoneum in two continuous ambulatory peritoneal
      dialysis patients from two different hospitals. Both patients used the
      Stay.Safe(r) system and bicaVera solution, whose extension tubing is not primed
      with fluid but air-filled, unlike that of the conventional solution bags. This
      fact, together with a handling fault common to both patients, resulted in the
      inflow of the air in the tubing of bicaVera bags into the peritoneal cavity
      during every exchange. We warn of this complication, which must be specifically
      pointed out during training, and we recommend providing the system with a
      mechanic device to prevent this handling fault. 

PMID- 25984157
TI  - Histological findings in two renal transplants accomplishing operational
      tolerance criteria.
AB  - Operational tolerance is defined as stable renal function in transplants without
      immunosuppression for at least 1 year. We present histological assessments of two
      patients with operational tolerance. The first withdrew immunosuppression in 2005
      and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria.
      The biopsy showed mild chronic tubulointerstitial changes without inflammation.
      The second withdrew immunosuppression in 2009 and maintains stable renal function
      (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural
      rejection and Class II anti-human leukocyte antigen antibodies were detected.
      These cases suggest that a renal biopsy may be useful to rule out subclinical
      pathology in patients with operational tolerance. 

PMID- 25984158
TI  - A painful skin rash in a patient with Stage V chronic kidney disease.

PMID- 25984160
TI  - Wunderlich's syndrome in spontaneous angiomyolipoma bleeding.

PMID- 25984159
TI  - Friendly fire.

PMID- 25984161
TI  - Hypercalcemia and large abdominal mass.

PMID- 25984163
TI  - Effects of continuous and intermittent trainings on exercise-induced hematuria
      and proteinuria in untrained adult females.

PMID- 25984162
TI  - Topical local anaesthetic cream causing persistent skin erythaema over
      haemodialysis graft.

PMID- 25984164
TI  - Hepatitis C virus transmission through sharing hemodialysis machines.

PMID- 25984165
TI  - The acute interstitial nephritis induced by azithromycin.

PMID- 25984166
TI  - Transformation of membranous nephropathy into antiglomerular-basement membrane
      glomerluonephritis.

PMID- 25984167
TI  - A dialysis patient with hyperammonaemia: inferior mesenteric-caval shunt as a
      cause of portal-systemic encephalopathy.

PMID- 25984168
TI  - Construction and DNA immunization of human renalase eukaryotic expression vector.

PMID- 25984169
TI  - Imaging in encapsulating peritoneal sclerosis.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare but very severe complication
      of long-term peritoneal dialysis (PD). Since the first reports on this disease in
      the eighties, several imaging techniques have been used for its diagnosis.
      Because of the rarity of this condition, uniformity in modality and protocols for
      abdominal imaging for diagnosis has been lacking overtime. Nowadays, computed
      tomography (CT) is most often used. In this review, we provide an overview of all
      imaging modalities that have been used overtime to diagnose EPS as a late
      complication of PD. Imaging features characteristic for EPS and advantages as
      well as shortcomings of all modalities are discussed. We believe that when EPS is
      suspected, CT with contrast enhancement should be the modality of first choice in
      clinical practice. 

PMID- 25984170
TI  - Coupled plasma filtration adsorption for the treatment of a patient with acute
      respiratory distress syndrome and acute kidney injury: a case report.
AB  - Coupled plasma filtration adsorption (CPFA) is an extracorporeal blood
      purification therapy based on non-specific pro- and anti-inflammatory mediator
      adsorption on a special resin cartridge coupled with continuous veno-venous
      haemofiltration or continuous veno-venous haemodiafiltration and is one of the
      emerging treatments for septic patients. However, in the literature, there are
      limited data about its efficacy in treating patients with acute diseases but
      without the traditional criteria for sepsis. We describe the case of a 43-year
      old male who developed acute respiratory distress syndrome secondary to pneumonia
      and acute kidney injury, whose clinical conditions rapidly improved after early
      CPFA therapy. 

PMID- 25984171
TI  - Precursor T-lymphoblastic lymphoma presenting as primary renal lymphoma with
      acute renal failure.
AB  - We report a case of acute renal failure (ARF) and bilateral nephromegaly in a
      patient with a history of Crohn's disease and treatment with azathioprine. Kidney
      biopsy revealed diffuse renal infiltration by precursor T-cell lymphoblastic
      lymphoma (T-LBL). At the time of diagnosis, no extrarenal manifestations of the
      lymphoma were detectable and therefore the lymphoma was categorized as primary
      renal lymphoma (PRL). Thus far, precursor T-LBL presenting as PRL has not been
      described before. We emphasize that in patients with ARF and bilateral renal
      enlargement, renal lymphoma is an important differential diagnostic
      consideration. 

PMID- 25984172
TI  - Is thrombotic microangiopathy a paraneoplastic phenomenon? Case report and review
      of the literature.
AB  - It is currently recognized that the pathogenesis of malignancy-associated
      thrombotic microangiopathy (TMA) is distinct from thrombotic thrombocytopenic
      purpura. This carries important implications in its classification and its
      management. Here, we report a case of occult malignancy presenting initially as
      acute kidney injury secondary to TMA and highlight the importance of considering
      an underlying malignancy in patients not responding to conventional therapy for
      TMA. 

PMID- 25984173
TI  - Acute kidney injury due to pulmonary embolism: the case for 'congestive renal
      failure'.
AB  - The development of acute kidney injury in patients with pulmonary embolism (PE)
      has not been well documented. We report a patient who developed acute oliguria in
      the setting of massive PE. Catheter embolectomy followed by ultrafiltration
      resulted in an immediate and dramatic improvement in urine output.
      Uncharacteristically, serum creatinine did not rise during the oliguric phase for
      several days until after embolectomy, and there were no metabolic derangements.
      Our observation that embolectomy and ultrafiltration helped with hemodynamics and
      renal perfusion despite decreased cardiac output suggests that right ventricular
      failure from both pressure and volume overload may have been central to this
      process. We review the older and recent literature in support of our
      observations. 

PMID- 25984174
TI  - Two novel mutations of lecithin:cholesterol acyltransferase (LCAT) gene and the
      influence of APOE genotypes on clinical manifestations.
AB  - Familial lecithin:cholesterol acyltransferase deficiency (FLD) is an autosomal
      recessive disorder characterized by corneal opacity, hemolytic anemia, low high
      density lipoprotein cholesterol (HDL-C) and proteinuria. Two novel
      lecithin:cholesterol acyltransferase (LCAT) mutations[c.278 C>T (p.Pro69Leu);
      c.950 T>C (p.Met293Thr)] were identified in a 27-year-old man and in a 30-year
      old woman, respectively. Both patients manifested corneal opacity, hemolytic
      anemia, low low-density lipoprotein cholesterol and HDL-C and proteinuria. Lipid
      deposits with vacuolar lucent appearance in glomerular basement membranes were
      observed in both cases. APOE genotype was also investigated: the first case
      results epsilon4/epsilon3, the second epsilon2/epsilon2; however, they shared a
      similar phenotype characterized by the presence of intermediate-density
      lipoproteins (IDL) remnant and the absence of lipoprotein-X. In conclusion, our
      findings suggest that APOE epsilon2/epsilon2 may not be the major determinant
      gene for the appearance of IDL in FLD patients. 

PMID- 25984175
TI  - Serum prolactin levels in a uremic child: effects of bilateral nephrectomy and
      kidney transplantation.
AB  - Elevated levels of serum prolactin (PRL) are common and well described in
      patients with chronic renal failure. We report the case of a 4-year-old girl who
      also presented with premature thelarche and transient galactorrhea. Neither
      peritoneal dialysis nor hemodialysis reduced her extremely elevated levels of
      PRL, which fluctuated from time to time, probably reflecting variations in
      lactotroph secretion rate. Bilateral nephrectomy (BN) was eventually followed by
      a progressive and significant rise in PRL levels, suggesting that even uremic
      kidneys can eliminate PRL through tubular breakdown. Kidney transplantation was
      responsible for a very abrupt normalization of PRL serum levels, much faster than
      that observed for creatinine. This confirms animal studies suggesting that
      elimination of PRL occurs both through glomerular filtration and tubular
      breakdown. We hypothesized that the seemingly precocious puberty may have
      resulted from a combination of growth hormone therapy, elevated PRL and a rise in
      estrogens through the aromatization of adrenal androgens. This case illustrates
      the impact of dialysis, BN and kidney transplantation on PRL, providing new
      knowledge on renal PRL metabolism. 

PMID- 25984176
TI  - A case of endocapillary glomerulonephritis associated with peripheral blood
      natural killer cell proliferation.
AB  - A 69-year-old male was admitted to our hospital due to rapidly progressive
      glomerulonephritis. A peripheral blood smear showed a marked increase in large
      granular lymphocytes. Flow cytometry analysis of the blood showed a marked
      increase in CD3-negative and CD56-positive natural killer (NK) cells. A renal
      biopsy showed a characteristic pathological pattern that involved endocapillary
      proliferation, a predominance of mononuclear cells and mesangiolysis.
      Prednisolone was administered, and the patient's renal function subsequently
      improved concomitant with the amelioration of NK cell proliferation. In our case,
      there was evidence of a strong association between NK cell proliferation and
      glomerulonephritis. 

PMID- 25984177
TI  - Long-term high-dose cholecalciferol in patients with heavy proteinuria.
AB  - Four patients presenting with heavy proteinuria, vitamin D deficiency and
      secondary hyperparathyroidism were treated with cholecalciferol for 1.5-3 years.
      Doses of 7143-14286 U/day were necessary to achieve the calcidiol target of >75
      nmol/L. The effect of dosing on calcidiol levels was inconsistent and there was
      no apparent relationship between changing calcidiol levels and intact parathyroid
      hormone (PTH) levels. Toxicity was not observed. This series suggests high doses
      of cholecalciferol over a prolonged period of time are necessary to achieve
      recommended calcidiol levels; however, the lack of an impact on PTH casts doubt
      on the suitability of the calcidiol target, in patients with heavy proteinuria. 

PMID- 25984178
TI  - Recurrent renal hyperparathyroidism due to parathyromatosis.
AB  - Parathyromatosis is the most severe type of recurrent secondary
      hyperparathyroidism (SHPT) after parathyroidectomy (PTX) in haemodialysis
      patients. It is difficult to completely remove all foci of parathyroid tissue and
      neck re-explorations are often required. Here, we report for the first time a
      case of recurrent SHPT due to parathyromatosis treated by radio-guided PTX. A
      haemodialysed 48-year-old woman with recurrent SHPT due to parathyromatosis was
      treated by radio-guided PTX. Preoperatively Ultrasonography, (99)Tc-SestaMIBI
      scintigraphy and magnetic resonances of the neck and thorax were performed. The
      preoperative imaging techniques detected four parathyroid nodules, while
      intraoperative gamma probe identified six nodules (three in atypical site). No
      frozen sections were performed during surgery. Post-operative intact parathyroid
      hormone levels were stabilized in the range 300-500 pg/mL during the 26 month
      follow-up by means of cinacalcet and paricalcitol therapy. In cases of
      parathyromatosis, the preoperative imaging techniques are inadequate, while
      intraoperative gamma probe is useful to detect the parathyroid tissue and allows
      a more extensive cytoreduction because it ensures the removal of undetectable and
      ectopic parathyroid foci. The operative time is reduced and frozen sections are
      unnecessary. However, the radio-guided PTX do not rule out parathyromatosis
      recurrence and complementary medical treatment is appropriate. 

PMID- 25984179
TI  - Kidney allograft failure due to acute phosphate nephropathy associated with
      severe secondary hyperparathyroidism.
AB  - Intratubular calcification is a common finding in renal allografts. However,
      possible harmful effect of this calcification is not well recognized, and
      allograft failure purely due to this condition has not been reported. We report a
      kidney transplant recipient who suffered from severe secondary
      hyperparathyroidism and unexplained early allograft failure. A diagnosis of acute
      phosphate nephropathy was made subsequently based on serial allograft biopsy
      findings. This case calls for a high index of suspicion to look for this rare
      cause of allograft dysfunction among high-risk patients. It also highlights the
      importance of good calcium-phosphate control before renal transplantation. 

PMID- 25984180
TI  - Falling through the cracks of vasculitis classification-a report of three
      patients.

PMID- 25984181
TI  - An unusual presentation of pheochromocytoma.

PMID- 25984182
TI  - Emerging role of radiological criteria for antemortem diagnosis of renal
      zygomycosis: an uncommon cause of acute renal failure.

PMID- 25984183
TI  - The risk of acute kidney injury following laparoscopic surgery in a chronic
      kidney disease patient.

PMID- 25984184
TI  - Cytomegalovirus in the transplanted kidney: a report of two cases and review of
      prophylaxis.

PMID- 25984185
TI  - Periodic fever syndrome with relapsing glomerulonephritis: a case report and
      teaching points.
AB  - We report a case of relapsing mesangial and endocapillary proliferative
      glomerulonephritis (GN) associated with a periodic fever syndrome. The patient
      presented 11 times in >4 years with acute febrile episode followed in 1-3 days by
      hematuria, thrombocytopenia and other symptoms of acute GN with variable severity
      of acute kidney injury. In three episodes, the patient required renal replacement
      therapy for 7, 10 and 2 treatments, respectively. Shortly after the acute
      symptoms of the febrile episode had resolved each time, the kidney function would
      recover and the serum creatinine would return to baseline. Two kidney biopsies
      obtained during separate episodes showed acute tubular injury along with
      morphological changes resembling post-infectious GN but with no clinical evidence
      to support an infectious etiology. Multiple treatment regimens were unable to
      control the disease. Symptoms were alleviated by rituximab but did not completely
      remit. Stable remission of the periodic fever and GN was finally achieved after
      anakinra therapy was initiated 18 months ago. Since then, the patient had several
      episodes of documented infection without high fever and nephritic kidney
      manifestations. His kidney function remained stable with normal serum creatinine.

PMID- 25984186
TI  - Smiling glomerulus reveals diagnosis in seronegative anti-glomerular basement
      membrane disease.

PMID- 25984187
TI  - Endosulfan and black urine.

PMID- 25984188
TI  - Prurigo nodularis in a woman with Stage-4 chronic kidney disease.

PMID- 25984189
TI  - A rare cause of hypokalaemia and metabolic alkalosis.

PMID- 25984190
TI  - Microscopic papillary tumor in a renal needle biopsy specimen for IgA
      nephropathy.

PMID- 25984191
TI  - Metastatic pulmonary calcification.

PMID- 25984192
TI  - Half and half nails.

PMID- 25984193
TI  - Dog walk: a simple way to improve chronic kidney disease patients' inactivity.

PMID- 25984194
TI  - Tacrolimus monotherapy in a patient with lupus flare using once-daily
      administration protocol.

PMID- 25984195
TI  - Age- and gender-adjusted eGFR to estimate baseline creatinine for RIFLE criteria.

PMID- 25984196
TI  - NDT Plus introduces the Clinical Kidney Journal.

PMID- 25984198
TI  - Scorpion sting nephropathy.
AB  - Scorpion envenomations are ubiquitous, but nephropathy is a rare manifestation,
      reported mainly from the Middle East and North Africa. Rapid venom redistribution
      from blood, delayed excretion from the kidneys, direct toxicity of venom enzymes,
      cytokine release and afferent arteriolar constriction have been seen in
      experimental animals. Haemoglobinuria, acute tubular necrosis, interstitial
      nephritis and haemolytic-uraemic syndrome have been documented in human victims
      of scorpion envenomation. Epidemiology, venom components and toxins, effects on
      the laboratory mammals especially the kidneys and reports of renal failure in
      humans are reviewed in this article. 

PMID- 25984199
TI  - Rapidly progressive renal failure-a rare presentation of granulomatous
      interstitial nephritis due to tuberculosis-case report and review of literature.
AB  - Granulomatous interstitial nephritis (GIN) is a rare manifestation of renal
      tuberculosis (TB). We report a case of rapidly progressive renal failure (RPRF),
      granulomatous inflammation of cervical lymph node and GIN as presenting
      manifestations of TB. Aspiration cytology of cervical lymph node showed
      granulomatous necrotizing inflammation with acid-fast bacilli (AFB). The renal
      biopsy and urine specimen did not show AFB. Urine polymerase chain reaction (PCR)
      for Mycobacterium tuberculosis was positive. We observe that GIN due to TB can
      present as RPRF and emphasize the value of PCR-based techniques in making a
      correct diagnosis. 

PMID- 25984197
TI  - Glycated albumin is the preferred marker for assessing glycaemic control in
      advanced chronic kidney disease.
AB  - Diabetic nephropathy is the most common aetiology of end-stage kidney disease
      (ESKD). Strict glycaemic control reduces the development and progression of
      diabetes-related complications, and there is evidence that improved metabolic
      control improves outcomes in diabetic subjects with advanced chronic kidney
      disease (CKD). Glycaemic control in people with kidney disease is complex.
      Changes in glucose and insulin homeostasis may occur as a consequence of loss of
      kidney function and dialysis. The reliability of measures of long-term glycaemic
      control is affected by CKD and the accuracy of glycated haemoglobin (HbA1c) in
      the setting of CKD and ESKD is questioned. Despite the altered character of
      diabetes in CKD, current guidelines for diabetes management are not specifically
      adjusted to this patient group. The validity of indicators of longer term
      glycaemic control has been the focus of increased recent research. This review
      discusses the current understanding of commonly used indicators of metabolic
      control (HbA1c, fructosamine, glycated albumin) in the setting of advanced CKD
      (Stages 4 and 5, glomerular filtration rate <30 mL/min/1.73m(2)). 

PMID- 25984200
TI  - A pseudo-dominant form of Gitelman's syndrome.
AB  - Gitelman's syndrome is an autosomal recessive salt losing nephropathy caused by
      inactivated mutations of the SLC12A3 gene, encoding the NaCl cotransporter of the
      distal convoluted tubule. We report a French family with five affected members
      over two generations suggesting a dominant transmission. After SLC12A3 sequencing
      of seven individuals, four mutations were detected. Pseudo-dominant transmission
      was explained by the union of a compound heterozygous woman (two mutations on one
      allele and one mutation on the other) with a heterozygous healthy man. This study
      shows the importance of complete genetic analysis of families with unusual
      presentation. 

PMID- 25984201
TI  - Haemodialysis-induced syncope due to Chiari II malformation.
AB  - Spina bifida (SB) is associated with chronic kidney disease as a result of
      vesicoureteric reflux. A proportion of patients progress to end-stage kidney
      disease (ESKD). Haemodialysis (HD) is probably the most common modality in ESKD,
      as intra-abdominal malformations and previous surgery can make peritoneal
      dialysis more challenging. The Chiari malformations also frequently occur in
      these patients. We report a case of recurrent syncope induced by HD in a patient
      with SB and the Chiari II malformation. Sparse data exist on the complications of
      HD in this patient population and on the approach to the management of dialysis
      induced syncope in these individuals. 

PMID- 25984202
TI  - C1q nephropathy in a patient with Gitelman syndrome.
AB  - Bartter syndrome can manifest in three different forms and is rarely concomitant
      with glomerular nephropathies. However, this association is more frequently
      observed in children. We report the case of a 50-year-old woman with Gitelman
      syndrome for the past 30 years who also had a nephrotic syndrome of recent
      appearance. Her renal biopsy revealed hyperplasia of the juxtaglomerular
      apparatus and mesangial deposits of C1q, with no clinical or serological evidence
      of systemic erythematous lupus. We have not found any reports of instances of
      association of Gitelman syndrome and nephrotic syndrome arising from C1q
      nephropathy in adult patients. Our case suggests the possible existence of an
      association between hypokalaemic tubular nephropathies and glomerular
      nephropathies that may cause nephrotic syndrome. 

PMID- 25984203
TI  - A 19-year-old at 37 weeks gestation with an acute acetylsalicylic acid overdose.
AB  - Acute salicylate overdose in pregnancy is potentially fatal for both the mother
      and fetus and presents a unique challenge in intensive care management. While
      suggested thresholds exist for hemodialysis in adults with toxic salicylate
      ingestion, it is unclear if these thresholds remain appropriate for the gravid
      patient, particularly given that medications such as acetylsalicylic acid may
      cross the placental barrier and accumulate in the fetal bloodstream. We describe
      a case of a gravid patient at ~37 weeks gestational age with a self-reported
      acetylsalicylic acid ingestion of 32.5 g and review prior cases of both acute and
      chronic salicylate ingestion in pregnancy in order to determine the clinical
      precedent for hemodialysis in this situation. 

PMID- 25984204
TI  - Madura's foot in a renal transplant patient: report of a case.
AB  - A 40-year-old kidney transplant male recipient was hospitalized for chronic
      abscess of the right foot in a context of immunodepression. The patient came from
      Djibouti and was in Belgium for a few days. He presented a right foot with a
      swelling localized on the first metatarsophalangeal joint which was excoriated
      (Figures 1 and 2) and was self-treated ineffectively with various local
      antiseptics for several months. He was in the operating room for an open biopsy
      done by plantar and dorsal approach to confirm the fungal infection. Treatment
      was not started with oral itraconazole because of the good evolution of the
      lesion. Pain diminished after a few days, and the patient was able to walk after
      a few weeks. 

PMID- 25984205
TI  - Extreme lactic acidosis type B associated with metformin treatment.
AB  - The elimination of metformin is exclusively through the kidneys and elevated
      plasma concentrations can cause lactic acidosis. We report a case of severe
      lactic acidosis (pH 6.60) occuring with ostensibly normal therapeutic doses of
      metformin in the setting of acute renal failure. Continuous veno-venous
      haemodiafiltration decreased plasma metformin concentrations from 266 lmol/L at
      presentation to 68 lmol/L, 21 h later. The patient improved rapidly. 

PMID- 25984206
TI  - Colonic necrosis and perforation due to calcium polystyrene sulfonate in a
      uraemic patient: a case report.
AB  - Sodium or calcium polystyrene sulfonate (Kayexalate or analog) is an ion-exchange
      resin commonly used to treat hyperkalaemia in patients with chronic kidney
      disease. It is known to cause digestive complications, such as nausea, vomiting
      and constipation. Although rare, colonic necrosis and perforation are very severe
      complications associated with the medication. In this case report, we present a
      case of calcium polystyrene sulfonate-induced colonic necrosis and perforation to
      remind clinicians of this rare, but dangerous, toxicity associated with this
      commonly used medication. 

PMID- 25984207
TI  - Successful renal transplantation in Muckle-Wells syndrome treated with anti-IL
      1beta-monoclonal antibody.
AB  - We report the first case of a 32-year-old woman with Muckle-Wells syndrome and
      biopsy-proven systemic AA amyloidosis and end-stage renal disease. She was
      treated with canakinumab 150 mg subcutaneously every 8 weeks and underwent renal
      transplantation. Fourteen months after renal transplanation, the patient had no
      flares of Muckle-Wells syndrome and no evidence of amyloidosis in the renal
      transplant under an excellent graft function and therapy with canakinumab. 

PMID- 25984208
TI  - POEMS syndrome with renal plasmacytoma and classic polyarteritis nodosa: a case
      report.
AB  - POEMS syndrome is a rare conglomeration of disorders associated with plasma cell
      dyscrasia. The acronym POEMS is derived from main features of the syndrome namely
      'polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin
      lesions'. Other clinical features include presence of sclerotic bone lesions,
      Castleman's disease, papilledema, pleural effusion, edema, ascites,
      erythrocytosis and thrombocytosis. Myeloma is the most common plasma cell
      dyscrasia associated with POEMS syndrome. Renal involvement is rare and renal
      biopsy is characterized by glomerular involvement with membranoproliferative
      glomerulonephritis and endothelial injury. We report a case of a 67-year-old male
      who presented with clinical features satisfying the diagnostic criteria of POEMS
      syndrome and had rapidly progressive renal failure. Renal biopsy showed extensive
      interstitial infiltration by plasma cells and concomitant presence of classic
      polyarteritis nodosa. Although association with small-vessel vasculitis has been
      reported in patients with POEMS syndrome, to the best of our knowledge, this is
      the first report of POEMS syndrome associated with medium-sized vessel
      vasculitis. 

PMID- 25984209
TI  - Tissue is the issue: a solitary cerebral lesion 15 years after kidney
      transplantation.
AB  - Primary toxoplasmosis and reactivation of latent infections occur in solid organ
      transplant recipients. However, solitary cerebral lesions due to toxoplasmosis
      are rare. In this case, a patient presented with a haemiparesis and a cerebral
      lesion. We expected to find cerebral post-transplant lymfoproliferative disorder
      because of positive Epstein-Barr virus by polymerase chain reaction in
      cerebrospinal fluid, but histological findings revealed Toxoplasma gondii
      bradyzoites and tachyzoites, illustrating the necessity of obtaining material for
      diagnostics in immunocompromised hosts. 

PMID- 25984210
TI  - Fibrillary glomerulonephritis: presenting as crescentic glomerulonephritis
      causing rapidly progressive renal failure.
AB  - We report an unusual case of fibrillary glomerulonephritis (FGN) presenting as
      rapidly progressive renal failure and extensive crescent formation along with
      linear staining of capillary walls of the glomeruli on immunofluorescence,
      mimicking anti-glomerular basement membrane (anti-GBM) antibody-mediated disease.
      Laboratory results for circulating anti-GBM antibodies were negative. The
      subsequent electron microscopic findings were that of presence of electron-dense
      deposits in the glomerular mesangium and capillary walls, comprising of non
      branching fibrils with an average diameter of 16 nm consistent with a diagnosis
      of FGN. This case illustrates the crucial role of electron microscopy in
      differential diagnosis of crescentic glomerulonephritis. 

PMID- 25984211
TI  - IgM antibodies towards pre-endothelial cells: strong indication for an
      association with accelerated rejection. A case report.
AB  - A 27-year-old woman developed a graft loss due to an accelerated humoral
      rejection after receiving a blood group identical, human leucocyte antigens (HLA)
      haploidentical living-related kidney, despite the fact that she did not refer any
      sensitization event before transplantation. The complement-dependent cytotoxicity
      and flow cytometry crossmatches were negative for T and B cells. Retrospectively,
      IgM antibodies against donor precursor endothelial Tie-2(+) cells were detected
      using a commercially available assay and the pre-transplant serum sample. This
      case illustrates the necessity of detection of other than the classical HLA
      directed antibodies prior organ grafting. 

PMID- 25984212
TI  - Nutcracker phenomenon presenting as loin pain haematuria syndrome.
AB  - A 19-year-old female presented with bilateral severe loin pain associated with
      recurrent macroscopic haematuria. A provisional diagnosis of loin pain haematuria
      syndrome was made; the severity and frequency of pain led to referral to the pain
      management service. Alternative diagnoses were considered. Although previous
      reports of obstruction of the left renal vein have not described pain of this
      severity, magnetic resonance angiography was performed; it showed obstruction of
      the left renal vein as it passed between the superior mesenteric artery and
      aorta, i.e. the nutcracker phenomenon. Both pain and haematuria resolved fully
      after autotransplantation. 

PMID- 25984213
TI  - Senior-Loken syndrome secondary to NPHP5/IQCB1 mutation in an Iranian family.
AB  - Senior-Loken syndrome (SLS) is a rare autosomal recessive disease characterized
      by nephronophthisis and early-onset retinal degeneration. We used a large Iranian
      family with SLS to establish a molecular genetic diagnosis. Following clinical
      evaluation, we undertook homozygosity mapping in two affected family members and
      mutational analysis in known SLS genes coinciding with regions of homozygosity.
      In a region of homozygosity coinciding with a known SLS locus on chromosome
      3q21.1, we found a homozygous non-sense mutation R332X in NPHP5/IQCB1. This is
      the first report of a molecular genetic diagnosis in an Iranian kindred with SLS.

PMID- 25984214
TI  - Hyponatraemia caused by LGI1-associated limbic encephalitis.
AB  - Limbic encephalitis (LE), once thought to be a rare paraneoplastic phenomenon, is
      increasingly diagnosed in patients without malignancy. Autoimmune LE has emerged
      as a distinct clinical entity. Autoantibodies to neuronal cell surface proteins
      have been described and may now be tested for. This has led to an exponential
      increase in the number of cases being reported. The most recently implicated
      autoantibody is to the leucine-rich anti-glioma 1 protein (LGI1). This protein is
      involved in synaptic transmission and inherited loss-of-function mutations cause
      autosomal dominant lateral temporal epilepsy. LGI1 is also expressed in specific
      tubules in the kidney. Anti-leucine-rich anti-glioma 1 protein (anti-LGI1) LE
      presents with sub acute onset of progressive neurological, cognitive and
      psychiatric disturbance. The condition is complicated in up to 60% of cases with
      severe and life threatening hyponatraemia. As well as causing significant
      morbidity, the co-existence of hyponatraemia may confuse the initial diagnosis.
      We present a case of anti-LGI1 which was complicated by hyponatraemia with a
      comprehensive review of the literature. 

PMID- 25984215
TI  - Minimal-change disease as a paraneoplastic syndrome in a patient with ovarian
      carcinoma.
AB  - Minimal-change disease (MCD) is an exceptional paraneoplastic presentation. We
      are describing the case of an ovarian paraneoplastic nephrotic syndrome. The
      kidney biopsy was consistent with MCD. Steroids and immunosuppressive therapy
      were given with no change in the nephrotic-range proteinuria. A complete
      resolution of the nephrotic syndrome was soon observed with improvement of her
      clinical condition after five cycles of chemotherapy with paclitaxel and
      carboplatin and tumor-debulking surgery. Ovarian carcinoma paraneoplastic
      nephrotic syndrome secondary to MCD is an extremely rare event, which is
      important to recognize since it is responsive to the standard chemotherapy. 

PMID- 25984216
TI  - Proteinuria and glomerular injury associated with the anti-angiogenesis drug
      VargatefTM.

PMID- 25984217
TI  - How plausible is transmission of hepatitis C virus via the haemodialysis circuit?

PMID- 25984218
TI  - Cloudy dialysate-reconsidering initial empiric therapy.

PMID- 25984219
TI  - Sepsis and a painful shoulder in a haemodialysis patient.

PMID- 25984220
TI  - Unusual skin lesions in a haemodialyzed patient.

PMID- 25984221
TI  - An elderly nursing home resident with unusual urine bag discoloration.

PMID- 25984222
TI  - Rhabdomyolysis and elevated liver function tests-what's the underlying cause?

PMID- 25984223
TI  - Successful management of angiomyolipoma of the left kidney.

PMID- 25984224
TI  - Bullous necrotizing cellulitis in kidney transplant recipient.

PMID- 25984225
TI  - Successful management of bilateral emphysematous pyelonephritis in end-stage
      polycystic kidneys: bilateral native nephrectomies and preservation of
      functioning renal transplant.

PMID- 25984226
TI  - Nutcracker phenomenon and idiopathic IgA nephropathy.

PMID- 25984227
TI  - The role of hypoxia-inducible factor-1 alpha in TEMPI syndrome.

PMID- 25984228
TI  - Common digital camera and urinary sediment analysis: a tool to be explored.

PMID- 25984229
TI  - Bilateral optic neuropathy-a rare uraemic manifestation of end-stage renal
      disease.

PMID- 25984230
TI  - An interaction between tacrolimus and pristinamycin resulting in an elevated
      tacrolimus level.

PMID- 25984231
TI  - The clinical spectrum and outcome of accidental wildfowl-mediated nicotinic plant
      poisoning.

PMID- 25984232
TI  - Reply.

PMID- 25984233
TI  - Comparing three diagnostic algorithms of posttraumatic stress in young children
      exposed to accidental trauma: an exploratory study.
AB  - BACKGROUND: Both the DSM-5 algorithm for posttraumatic stress disorder (PTSD) in
      children 6 years and younger and Scheeringa's alternative PTSD algorithm (PTSD
      AA) aim to be more developmentally sensitive for young children than the DSM-IV
      PTSD algorithm. However, very few studies compared the three algorithms
      simultaneously. The current study explores diagnostic outcomes of the three
      algorithms in young child survivors of accidental trauma. METHODS: Parents of 98
      young children (0-7 years) involved in an accident between 2006 and 2012
      participated in a semi-structured telephone interview. Child posttraumatic stress
      symptoms (PTSS) were measured with the Anxiety Disorders Interview Schedule for
      DSM-IV-Child Version (ADIS-C/P), complemented with items from the Diagnostic
      Infant and Preschool Assessment (DIPA). Descriptive statistics were used to
      analyze the characteristics of the children, accident related information and PTS
      symptoms. We compared the three PTSD algorithms in order to explore the
      diagnostic outcomes. RESULTS: A total of 9 of the children (9.2 %) showed
      substantial PTSS. Of these children 2 met the criteria of all three algorithms, 7
      met both the DSM-5 subtype for children 6 years and younger and the PTSD-AA
      algorithm, and 2 did not fully meet any of the algorithms (subsyndromal PTSD).
      CONCLUSIONS: For young children, the DSM-5 subtype for children 6 years and
      younger and the PTSD-AA algorithm appear to be better suited than the previous
      DSM-IV algorithm. It remains important that clinicians pay attention to children
      with subsyndromal PTSD.

PMID- 25984234
TI  - Automated nutrient screening system enables high-throughput optimisation of
      microalgae production conditions.
AB  - BACKGROUND: Microalgae provide an excellent platform for the production of high
      value-products and are increasingly being recognised as a promising production
      system for biomass, animal feeds and renewable fuels. RESULTS: Here, we describe
      an automated screen, to enable high-throughput optimisation of 12 nutrients for
      microalgae production. Its miniaturised 1,728 multiwell format allows multiple
      microalgae strains to be simultaneously screened using a two-step process. Step 1
      optimises the primary elements nitrogen and phosphorous. Step 2 uses Box-Behnken
      analysis to define the highest growth rates within the large multidimensional
      space tested (Ca, Mg, Fe, Mn, Zn, Cu, B, Se, V, Si) at three levels (-1, 0, 1).
      The highest specific growth rates and maximum OD750 values provide a measure for
      continuous and batch culture. CONCLUSION: The screen identified the main nutrient
      effects on growth, pairwise nutrient interactions (for example, Ca-Mg) and the
      best production conditions of the sampled statistical space providing the basis
      for a targeted full factorial screen to assist with optimisation of algae
      production.

PMID- 25984236
TI  - Indirect and direct relations between aerobic fitness, physical activity, and
      academic achievement in elementary school students.
AB  - BACKGROUND: There is evidence to suggest that increasing physical activity (PA)
      improves academic achievement (AA) in children and that aerobic fitness is
      associated with both cognitive function and AA. However, it is not known how
      these variables are interrelated and analyses with adequate control for
      socioeconomic variables are needed. It was hypothesized that PA would not
      directly affect AA but would have an indirect effect on AA through its effect on
      aerobic fitness. The purpose of this study was to test this hypothesized
      mediation using path analysis. METHODS: Cross-sectional data including AA,
      aerobic fitness, and daily PA assessed through accelerometry were collected from
      a large sample (N = 687) of 2nd and 3rd grade students. Demographic data were
      assessed via parent self-report. RESULTS: A total of 401 students wore the
      accelerometer for at least 10 hours on 3 days or more and were included in the
      final path analysis to evaluate potential relations among PA (predictor), aerobic
      fitness (mediator), and WIAT-III subtest standard scores (outcomes; i.e.,
      reading, spelling, and mathematics). Findings showed a direct effect of PA on
      aerobic fitness (b = 0.009, p < 0.001) and an indirect effect (mediation) of PA
      via fitness on math achievement (b = 0.003, p < 0.01) after controlling for
      student's grade, gender, body mass index, mother's education level, and household
      income, as well as intraclass correlations among classes and schools. Neither PA
      nor aerobic fitness were correlated with WIAT-III reading or spelling scores.
      CONCLUSIONS: Mediation analysis indicated that PA exerted an influence on math
      achievement through its effects on aerobic fitness but was not associated with
      reading or spelling achievement scores.

PMID- 25984235
TI  - Prospects for clinical use of reprogrammed cells for autologous treatment of
      macular degeneration.
AB  - Since the discovery of induced pluripotent stem cells (iPSC) in 2006, the
      symptoms of many human diseases have been reversed in animal models with iPSC
      therapy, setting the stage for future clinical development. From the animal data
      it is clear that iPSC are rapidly becoming the lead cell type for cell
      replacement therapy and for the newly developing field of iPSC-derived body organ
      transplantation. The first human pathology that might be treated in the near
      future with iPSC is age-related macular degeneration (AMD), which has recently
      passed the criteria set down by regulators for phase I clinical trials with
      allogeneic human embryonic stem cell-derived cell transplantation in humans.
      Given that iPSC are currently in clinical trial in Japan (RIKEN) to treat AMD,
      the establishment of a set of international criteria to make clinical-grade iPSC
      and their differentiated progeny is the next step in order to prepare for future
      autologous cell therapy clinical trials. Armed with clinical-grade iPSC, we can
      then specifically test for their threat of cancer, for proper and efficient
      differentiation to the correct cell type to treat human disease and then to
      determine their immunogenicity. Such a rigorous approach sets a far more relevant
      paradigm for their intended future use than non-clinical-grade iPSC. This review
      focuses on the latest developments regarding the first possible use of iPSC
      derived retinal pigment epithelial cells in treating human disease, covers data
      gathered on animal models to date and methods to make clinical-grade iPSC,
      suggests techniques to ensure quality control and discusses possible clinical
      immune responses. 

PMID- 25984237
TI  - A bibliometric analysis on tobacco regulation investigators.
AB  - BACKGROUND: To facilitate the implementation of the Family Smoking Prevention and
      Tobacco Control Act of 2009, the Federal Drug Agency (FDA) Center for Tobacco
      Products (CTP) has identified research priorities under the umbrella of tobacco
      regulatory science (TRS). As a newly integrated field, the current boundaries and
      landscape of TRS research are in need of definition. In this work, we conducted a
      bibliometric study of TRS research by applying author topic modeling (ATM) on
      MEDLINE citations published by currently-funded TRS principle investigators
      (PIs). RESULTS: We compared topics generated with ATM on dataset collected with
      TRS PIs and topics generated with ATM on dataset collected with a TRS keyword
      list. It is found that all those topics show a good alignment with FDA's funding
      protocols. More interestingly, we can see clear interactive relationships among
      PIs and between PIs and topics. Based on those interactions, we can discover how
      diverse each PI is, how productive they are, which topics are more popular and
      what main components each topic involves. Temporal trend analysis of key words
      shows the significant evaluation in four prime TRS areas. CONCLUSIONS: The
      results show that ATM can efficiently group articles into discriminative
      categories without any supervision. This indicates that we may incorporate ATM
      into author identification systems to infer the identity of an author of articles
      using topics generated by the model. It can also be useful to grantees and
      funding administrators in suggesting potential collaborators or identifying those
      that share common research interests for data harmonization or other purposes.
      The incorporation of temporal analysis can be employed to assess the change over
      time in TRS as new projects are funded and the extent to which new research
      reflects the funding priorities of the FDA.

PMID- 25984240
TI  - Luscus: molecular viewer and editor for MOLCAS.
AB  - The novel program for graphical display and editing of molecular systems, luscus,
      is described. The program allows fast and easy building and/or editing different
      molecular structures, up to several thousands of atoms large. Luscus is able to
      visualise dipole moments, normal modes, molecular orbitals, electron densities
      and electrostatic potentials. In addition, simple geometrical objects can be
      rendered in order to reveal a geometrical feature or a physical quantity. The
      program is developed as a graphical interface for the MOLCAS program package,
      however its adaptive nature makes possible to use luscus with other computational
      program packages and chemical formats. All data files are opened via simple plug
      ins which makes easy to implement a new file format in luscus. The easiness of
      editing molecular geometries makes luscus suitable for teaching students chemical
      concepts and molecular modelling. Graphical AbstractScreenshot of luscus program
      showing molecular orbital. 

PMID- 25984239
TI  - Gene expression profiling reveals potential prognostic biomarkers associated with
      the progression of heart failure.
AB  - BACKGROUND: Heart failure (HF) is the most common cause of morbidity and
      mortality in developed countries. Here, we identify biologically relevant
      transcripts that are significantly altered in the early phase of myocardial
      infarction and are associated with the development of post-myocardial infarction
      HF. METHODS: We collected peripheral blood samples from patients with ST-segment
      elevation myocardial infarction (STEMI): n = 111 and n = 41 patients from the
      study and validation groups, respectively. Control groups comprised patients with
      a stable coronary artery disease and without a history of myocardial infarction.
      Based on plasma NT-proBNP level and left ventricular ejection fraction parameters
      the STEMI patients were divided into HF and non-HF groups. Microarrays were used
      to analyze mRNA levels in peripheral blood mononuclear cells (PBMCs) isolated
      from the study group at four time points and control group. Microarray results
      were validated by RT-qPCR using whole blood RNA from the validation group.
      RESULTS: Samples from the first three time points (admission, discharge, and 1
      month after AMI) were compared with the samples from the same patients collected
      6 months after AMI (stable phase) and with the control group. The greatest
      differences in transcriptional profiles were observed on admission and they
      gradually stabilized during the follow-up. We have also identified a set of genes
      the expression of which on the first day of STEMI differed significantly between
      patients who developed HF after 6 months of observation and those who did not.
      RNASE1, FMN1, and JDP2 were selected for further analysis and their early up
      regulation was confirmed in HF patients from both the study and validation
      groups. Significant correlations were found between expression levels of these
      biomarkers and clinical parameters. The receiver operating characteristic (ROC)
      curves indicated a good prognostic value of the genes chosen. CONCLUSIONS: This
      study demonstrates an altered gene expression profile in PBMCs during acute
      myocardial infarction and through the follow-up. The identified gene expression
      changes at the early phase of STEMI that differentiated the patients who
      developed HF from those who did not could serve as a convenient tool contributing
      to the prognosis of heart failure.

PMID- 25984238
TI  - Occupancy by key transcription factors is a more accurate predictor of enhancer
      activity than histone modifications or chromatin accessibility.
AB  - BACKGROUND: Regulated gene expression controls organismal development, and
      variation in regulatory patterns has been implicated in complex traits. Thus
      accurate prediction of enhancers is important for further understanding of these
      processes. Genome-wide measurement of epigenetic features, such as histone
      modifications and occupancy by transcription factors, is improving enhancer
      predictions, but the contribution of these features to prediction accuracy is not
      known. Given the importance of the hematopoietic transcription factor TAL1 for
      erythroid gene activation, we predicted candidate enhancers based on genomic
      occupancy by TAL1 and measured their activity. Contributions of multiple features
      to enhancer prediction were evaluated based on the results of these and other
      studies. RESULTS: TAL1-bound DNA segments were active enhancers at a high rate
      both in transient transfections of cultured cells (39 of 79, or 56%) and
      transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1
      did not help distinguish TAL1-bound DNA segments as active versus inactive
      enhancers, nor did the density of regulation-related histone modifications. A
      meta-analysis of results from this and other studies (273 tested predicted
      enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4
      methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most
      accurate predictors of enhancer activity, with a success rate over 80% and a
      median threefold increase in activity. Chromatin accessibility assays and the
      histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers,
      but they have high false positive rates unless transcription factor occupancy is
      also included. CONCLUSIONS: Occupancy by key transcription factors such as TAL1,
      GATA1, SMAD1, and EP300, along with evidence of transcription, improves the
      accuracy of enhancer predictions based on epigenetic features.

PMID- 25984241
TI  - SpeckTackle: JavaScript charts for spectroscopy.
AB  - BACKGROUND: Spectra visualisation from methods such as mass spectroscopy,
      infrared spectroscopy or nuclear magnetic resonance is an essential part of every
      web-facing spectral resource. The development of an intuitive and versatile
      visualisation tool is a time- and resource-intensive task, however, most
      databases use their own embedded viewers and new databases continue to develop
      their own viewers. RESULTS: We present SpeckTackle, a custom-tailored JavaScript
      charting library for spectroscopy in life sciences. SpeckTackle is cross-browser
      compatible and easy to integrate into existing resources, as we demonstrate for
      the MetaboLights database. Its default chart types cover common visualisation
      tasks following the de facto 'look and feel' standards for spectra visualisation.
      CONCLUSIONS: SpeckTackle is released under GNU LGPL to encourage uptake and reuse
      within the community. The latest version of the library including examples and
      documentation on how to use and extend the library with additional chart types is
      available online in its public repository.

PMID- 25984243
TI  - SERPINB3 (serpin peptidase inhibitor, clade B (ovalbumin), member 3).
AB  - Review on SERPINB3, with data on DNA/RNA, on the protein encoded and where the
      gene is implicated.

PMID- 25984242
TI  - Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer's
      disease: a voxel-based lesion mapping study.
AB  - INTRODUCTION: White matter (WM) magnetic resonance imaging (MRI) hyperintensities
      are common in Alzheimer's disease (AD), but their pathophysiological relevance
      and relationship to genetic factors are unclear. In the present study, we
      investigated potential apolipoprotein E (APOE)-dependent effects on the extent
      and cognitive impact of WM hyperintensities in patients with AD. METHODS: WM
      hyperintensity volume on fluid-attenuated inversion recovery images of 201
      patients with AD (128 carriers and 73 non-carriers of the APOE epsilon4 risk
      allele) was determined globally as well as regionally with voxel-based lesion
      mapping. Clinical, neuropsychological and MRI data were collected from
      prospective multicenter trials conducted by the German Dementia Competence
      Network. RESULTS: WM hyperintensity volume was significantly greater in non
      carriers of the APOE epsilon4 allele. Lesion distribution was similar among
      epsilon4 carriers and non-carriers. Only epsilon4 non-carriers showed a
      correlation between lesion volume and cognitive performance. CONCLUSION: The
      current findings indicate an increased prevalence of WM hyperintensities in non
      carriers compared with carriers of the APOE epsilon4 allele among patients with
      AD. This is consistent with a possibly more pronounced contribution of
      heterogeneous vascular risk factors to WM damage and cognitive impairment in
      patients with AD without APOE epsilon4-mediated risk.

PMID- 25984244
TI  - Managing the advanced cancer patient in the Australian emergency department
      environment: findings from a national survey of emergency department clinicians.
AB  - BACKGROUND: Delivery of care to people with advanced cancer in the emergency
      department (ED) is complicated by competing service demands, workloads and
      physical design constraints. We explored emergency clinicians' attitudes to the
      ED environment when caring for patients who present with advanced cancer, and how
      these attitudes are affected by access to palliative care services, palliative
      care education, staff type, ED experience and patient demographic, hospital type
      and region. METHODS: We electronically surveyed clinicians from the College of
      Emergency Nursing Australasia, Australian College of Emergency Nursing and
      Australasian College for Emergency Medicine working in an Australian ED. RESULTS:
      Respondents were 444 doctors and 237 nurses. They reported overcrowding, noise,
      lack of time and privacy as barriers to care. Most (93.3%) agreed/strongly agreed
      that the dying patient should be allocated private space in ED. 73.6% (451) felt
      unable to provide a desired level of care to advanced cancer patients in ED.
      Clinician attitudes were affected by staff type, experience, ED demographic and
      hospital type, but not education in palliative care. CONCLUSIONS: ED environments
      place pressure on clinicians delivering care to people with advanced cancer.
      Integrating palliative care services in ED and redesigning EDs to better match
      its multifaceted functions should be considered.

PMID- 25984245
TI  - Erratum: Self-referred patients at the Emergency Department: patient
      characteristics, motivations, and willingness to make a copayment.
AB  - [This corrects the article DOI: 10.1186/s12245-014-0030-7.]. 

PMID- 25984246
TI  - How much hamstring graft needs to be in the femoral tunnel? A MOON cohort study.
AB  - BACKGROUND: Recent evidence that smaller hamstring graft diameter is associated
      with increased failure risk following anterior cruciate ligament (ACL)
      reconstruction has increased the popularity of graft configurations that increase
      graft diameter at the expense of graft length. A key question is how much graft
      needs to be in contact with the femoral tunnel to ensure that healing occurs. We
      hypothesize that no difference in two-year patient-reported outcomes or failure
      risk exists based on the amount of graft in the femoral tunnel. METHODS: Through
      the use of prospectively collected cohort data augmented with retrospective chart
      review, 120 of 181 consecutive patients (66.3 %) undergoing primary ACL
      reconstruction with hamstring autograft were evaluated. Patient and surgical
      factors along with pre-operative and two-year postoperative knee injury and
      osteoarthritis outcome score (KOOS) and International Knee Documentation
      Committee (IKDC) scores and whether each patient underwent revision ACL
      reconstruction during the two-year follow-up period were recorded. RESULTS: No
      differences in two-year patient-reported outcome scores were noted between
      patients with graft length in the femoral tunnel less than 25 mm and those with
      graft length in the femoral tunnel of at least 25 mm. Controlling for age, sex,
      BMI, and femoral tunnel technique, no correlation was noted between KOOS or IKDC
      scores and either the length of graft in the femoral tunnel or the contact area
      between the graft and the tunnel. CONCLUSIONS: Variation of the length of
      hamstring autograft in the femoral tunnel between 14 and 35 mm does not predict
      KOOS or IKDC scores at 2 years postoperative.

PMID- 25984247
TI  - Environmental chemicals and DNA methylation in adults: a systematic review of the
      epidemiologic evidence.
AB  - Current evidence supports the notion that environmental exposures are associated
      with DNA-methylation and expression changes that can impact human health. Our
      objective was to conduct a systematic review of epidemiologic studies evaluating
      the association between environmental chemicals with DNA methylation levels in
      adults. After excluding arsenic, recently evaluated in a systematic review, we
      identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on
      nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and
      perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic
      hydrocarbons). The selected articles reported quantitative methods to determine
      DNA methylation including immunocolorimetric assays for total content of genomic
      DNA methylation, and microarray technologies, methylation-specific quantitative
      PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA
      methylation content of genomic sites such as gene promoters, LINE-1, Alu
      elements, and others. Considering consistency, temporality, strength, dose
      response relationship, and biological plausibility, we concluded that the current
      evidence is not sufficient to provide inference because differences across
      studies and limited samples sizes make it difficult to compare across studies and
      to evaluate sources of heterogeneity. Important questions for future research
      include the need for larger and longitudinal studies, the validation of findings,
      and the systematic evaluation of the dose-response relationships. Future studies
      should also consider the evaluation of epigenetic marks recently in the research
      spotlight such as DNA hydroxymethylation and the role of underlying genetic
      variants. 

PMID- 25984248
TI  - Human Cardiac Function Simulator for the Optimal Design of a Novel Annuloplasty
      Ring with a Sub-valvular Element for Correction of Ischemic Mitral Regurgitation.
AB  - Ischemic mitral regurgitation is associated with substantial risk of death. We
      sought to: (1) detail significant recent improvements to the Dassault Systemes
      human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal
      cardiac function as well as pathologic function in the setting of posterior left
      ventricular (LV) papillary muscle infarction; and (3) debut our novel device for
      correction of ischemic mitral regurgitation. We synthesized two recent studies of
      human myocardial mechanics. The first study presented the robust and integrative
      finite element HCFS. Its primary limitation was its poor diastolic performance
      with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine
      tissue parameters. The second study derived improved diastolic myocardial
      material parameters using in vivo MRI data from five normal human subjects. We
      combined these models to simulate ischemic mitral regurgitation by
      computationally infarcting an LV region including the posterior papillary muscle.
      Contact between our novel device and the mitral valve apparatus was simulated
      using Dassault Systemes SIMULIA software. Incorporating improved cardiac geometry
      and diastolic myocardial material properties in the HCFS resulted in a realistic
      LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle
      caused regurgitant mitral valve mechanics. Implementation of our novel device
      corrected valve dysfunction. Improvements in the current study to the HCFS permit
      increasingly accurate study of myocardial mechanics. The first application of
      this simulator to abnormal human cardiac function suggests that our novel
      annuloplasty ring with a sub-valvular element will correct ischemic mitral
      regurgitation. 

PMID- 25984249
TI  - A Technical Review of Minimally Invasive Mitral Valve Replacements.
AB  - Mitral regurgitation is one of the most common forms of heart valve disorder,
      which may result in heart failure. Due to the rapid ageing of the population,
      surgical repair and replacement treatments, which have represented an effective
      treatment in the past, are now unsuitable for about half of symptomatic patients,
      who are judged high-risk. Encouraged by the positive experience with
      transcatheter aortic valves and percutaneous reconstructive mitral treatments, a
      number of research groups are currently engaged in the development of minimally
      invasive approaches for the functional replacement of the mitral valve. The first
      experiences have clearly demonstrated that the approach is feasible and
      promising, though significant progress is still required in the prostheses design
      and implantation procedures before the treatment can establish as a safe and
      effective solution. This review analyses the devices currently at a most advanced
      stage of development, describing their main features and the technical solutions
      that they adopt in order to respond to the functional requirements of the most
      challenging of the heart valves. 

PMID- 25984250
TI  - B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice.
AB  - Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor
      activator of NF-kappaB ligand (RANKL) is the key effector cytokine for
      osteoclastogenesis and bone resorption, and is moderated by its decoy receptor
      osteoprotegerin (OPG). The development of an inflammatory environment during
      aging leads to increased bone resorption and loss of bone mineral density (BMD).
      Interestingly, animal and clinical studies show that OPG is actually increased in
      aging but fails to fully compensate for endogenous RANKL. Osteoblast- and B
      lineage cells are significant sources of physiological OPG, however osteoblast
      OPG production declines with age, suggesting that elevated OPG in aging may be a
      consequence of changes in B cell function. In this study we examined BMD and
      indices of trabecular bone structure during aging, and B cell production of both
      RANKL and OPG in young and aged mice. Our data reveal significant loss of BMD and
      trabecular structure with age commensurate with significantly elevated
      concentrations of both OPG and RANKL in aged mice, and a decline in B cell
      populations in aged animals. Taken together our data suggest that B cells may be
      responsible for the elevated concentrations of OPG during aging and are essential
      to counteract excessive age-associated bone resorption. Paradoxically, B cells
      themselves likely contribute RANKL in aging and the loss of B cells with age may
      further contribute to the imbalance in OPG relative to RANKL that predisposes age
      associated bone loss.

PMID- 25984251
TI  - A Review of the Prostatic Urethral Lift for Lower Urinary Tract Symptoms: Symptom
      Relief, Flow Improvement, and Preservation of Sexual Function in Men With Benign
      Prostatic Hyperplasia.
AB  - Prostatic urethral lift (PUL) has been shown to be a safe, effective treatment
      option for lower urinary tract symptoms secondary to benign prostatic
      hyperplasia. Discomfort with PUL is similar to that with rigid cystoscopy and can
      be tolerated with local anesthesia in an office setting. Of those who are given
      voiding trials, 70-80 % of subjects do not require a catheter. Subjects often
      quickly return to pre-operative activity level with minimal absence from work.
      Symptom relief can start within 2 weeks and be sustained through 2 years. Urinary
      flow rate improvements have been shown to be durable through 2 years. The most
      common adverse effects are dysuria, hematuria, pain, and urgency which are
      typically mild to moderate and transient. Sexual function appears to be preserved
      after PUL with no reported new-onset erectile dysfunction or anejaculation
      events. The retreatment rate is reported to be 7.5 % at 2 years.

PMID- 25984252
TI  - Prevalence and Behavioral Correlates of Depression and Anxiety Among Male Sex
      Workers in Vietnam.
AB  - OBJECTIVES: This study assessed depression and anxiety symptoms, and their
      association with high-risk sexual and drug behaviors, among male sex workers in
      three Vietnamese cities. METHODS: Male sex workers ages 16 to 35 completed an
      interview that included the CES-D to assess depressive symptoms and the BAI to
      assess anxiety symptoms, as well as questions assessing drug and sexual risk
      practices. RESULTS: A majority of participants reported depressive symptomatology
      although fewer report symptoms of anxiety. Risky sexual and drug use practices
      predicted both types of symptoms. CONCLUSIONS: Mental distress is associated with
      drug and sexual risk among male sex workers.

PMID- 25984253
TI  - A BAYESIAN NONPARAMETRIC MIXTURE MODEL FOR SELECTING GENES AND GENE SUBNETWORKS.
AB  - It is very challenging to select informative features from tens of thousands of
      measured features in high-throughput data analysis. Recently, several
      parametric/regression models have been developed utilizing the gene network
      information to select genes or pathways strongly associated with a
      clinical/biological outcome. Alternatively, in this paper, we propose a
      nonparametric Bayesian model for gene selection incorporating network
      information. In addition to identifying genes that have a strong association with
      a clinical outcome, our model can select genes with particular expressional
      behavior, in which case the regression models are not directly applicable. We
      show that our proposed model is equivalent to an infinity mixture model for which
      we develop a posterior computation algorithm based on Markov chain Monte Carlo
      (MCMC) methods. We also propose two fast computing algorithms that approximate
      the posterior simulation with good accuracy but relatively low computational
      cost. We illustrate our methods on simulation studies and the analysis of
      Spellman yeast cell cycle microarray data.

PMID- 25984254
TI  - Young athletes.

PMID- 25984255
TI  - Subscapularis tears and lesser tuberosity avulsion fractures in the pediatric
      patient.
AB  - BACKGROUND: Pediatric subscapularis tears are known to be rare injuries. They are
      often associated with an avulsion fragment of the lesser tuberosity leading to
      dual description in the literature of either subscapularis tear or lesser
      tuberosity avulsion. Historically, they were managed nonoperatively; however,
      outcomes have improved with operative management. Nonoperative management often
      led to bony overgrowth at the lesser tuberosity that limited motion. The
      literature is limited to case reports and a few small case series, often not
      restricted to pediatric patients. STUDY DESIGN: Case series. LEVEL OF EVIDENCE:
      Level 5. METHODS: Radiographic and operative databases were retrospectively
      reviewed to identify pediatric patients with subscapularis tears or lesser
      tuberosity avulsions in the past 10 years. RESULTS: Five cases of pediatric
      subscapularis tears were identified that underwent operative management. Of the 5
      cases, 4 had delayed presentation. In 1 case, the lesser tuberosity fragment was
      initially missed on radiographic imaging. All patients underwent operative
      management. CONCLUSION: These cases add to the body of knowledge of a rare
      pediatric injury that is commonly missed or diagnosis delayed. The importance of
      suspicion in the adolescent male patient without instability and unrelenting
      shoulder pain is stressed. Additionally, the importance of early magnetic
      resonance imaging with suspicion as well as an axillary view of the shoulder is
      demonstrated. As with all rare entities, it is important to disseminate
      information on natural history and interventions for this injury.

PMID- 25984257
TI  - Assessment of parental knowledge and attitudes toward pediatric sports-related
      concussions.
AB  - BACKGROUND: Parents of young athletes play a major role in the identification and
      management of sports-related concussions. However, they are often unaware of the
      consequences of concussions and recommended management techniques. HYPOTHESIS:
      This study quantitatively assessed parental understanding of concussions to
      identify specific populations in need of additional education. We predicted that
      parents with increased education and prior sports- and concussion-related
      experience would have more knowledge and safer attitudes toward concussions.
      STUDY DESIGN: Cross-sectional survey. LEVEL OF EVIDENCE: Level 5. METHODS:
      Participants were parents of children brought to a pediatric hospital and 4
      satellite clinics for evaluation of orthopaedic injuries. Participants completed
      a validated questionnaire that assessed knowledge of concussion symptoms,
      attitudes regarding diagnosis and return-to-play guidelines, and previous sports-
      and concussion-related experience. RESULTS: Over 8 months, 214 parents completed
      surveys. Participants scored an average of 18.4 (possible, 0-25) on the
      Concussion Knowledge Index and 63.1 (possible, 15-75) on the Concussion Attitude
      Index. Attitudes were safest among white women, and knowledge increased with
      income and education levels. Previous sports experience did not affect knowledge
      or attitudes, but parents who reported experiencing an undiagnosed concussion had
      significantly better concussion knowledge than those who did not. CONCLUSION:
      Parents with low income and education levels may benefit from additional
      concussion-related education. CLINICAL RELEVANCE: There exist many opportunities
      for improvement in parental knowledge and attitudes about pediatric sports
      related concussions. Ongoing efforts to understand parental knowledge of
      concussions will inform the development of a strategic and tailored approach to
      the prevention and management of pediatric concussions.

PMID- 25984256
TI  - Evaluation and management of patellar instability in pediatric and adolescent
      athletes.
AB  - CONTEXT: The rising popularity and intensity of youth sports has increased the
      incidence of patellar dislocation. These sports-related injuries may be
      associated with significant morbidity in the pediatric population. Treatment
      requires understanding and attention to the unique challenges in the skeletally
      immature patient. EVIDENCE ACQUISITION: PubMed searches spanning 1970-2013. STUDY
      DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: Although
      nonoperative approaches are most often suitable for first-time patellar
      dislocations, surgical treatment is recommended for acute fixation of displaced
      osteochondral fractures sustained during primary instability and for patellar
      realignment in the setting of recurrent instability. While a variety of
      procedures can prevent recurrence, the risk of complications is not minimal.
      CONCLUSION: Patellar stabilization and realignment procedures in skeletally
      immature patients with recurrent patellar dislocation can effectively treat
      patellar instability without untoward effects on growth if careful surgical
      planning incorporates protection of growth parameters in the skeletally immature
      athlete.

PMID- 25984258
TI  - Anterior cruciate ligament injuries in pediatric athletes presenting to sports
      medicine clinic: a comparison of males and females through growth and
      development.
AB  - BACKGROUND: Limited data exist regarding the effect of the growth process on
      anterior cruciate ligament (ACL) injury risk in male versus female children.
      HYPOTHESIS: The proportion of ACL injuries/sports injuries presenting to clinic
      will vary by age, sex, and body mass index (BMI). STUDY DESIGN: Cross-sectional
      epidemiologic study. LEVEL OF EVIDENCE: Level 3. METHODS: The study group
      consisted of a randomly selected 5% probability sample of all children 5 to 17
      years of age presenting to a sports medicine clinic from January 1, 2000 to
      December 31, 2009; 2133 charts were reviewed. Data collected included
      demographics, height and weight, injury mechanism, diagnosis, treatment, previous
      injury, and organized sports. RESULTS: A total of 206 ACL tears were analyzed
      (104 girls, 102 boys). Girls were slightly older than boys (15.1 +/- 1.7 vs 14.3
      +/- 2.1 years; P < 0.01). Male-female comparison of ACL injury/total injury by
      age revealed that girls had a steeper increase by age than boys. Among 5- to 12
      year-olds, boys had a higher ACL injury/total injury ratio than girls (all P <
      0.01). Children 13 to 17 years of age showed no significant difference for sex in
      ACL injury/total injury ratio. As age advanced, the proportion of ACL
      injuries/total injuries increased for both girls (P < 0.01) and boys (P = 0.04).
      BMI was independently associated with an ACL injury (P < 0.01). CONCLUSION: The
      proportion of ACL injuries/total injuries was similar for boys and girls aged 13
      to 17 years. Girls showed a significantly steeper increase in ACL injury
      proportion versus boys through puberty. CLINICAL RELEVANCE: This study will
      increase clinician awareness of ACL injury occurrence in young male and female
      athletes 5 to 12 years of age. Injury prevention efforts should target young
      girls before the onset of puberty and before injury occurs.

PMID- 25984259
TI  - Surgical treatment of clavicle fractures in the adolescent athlete.
AB  - CONTEXT: Current literature has clearly shown that the indications for surgical
      treatment of clavicle fractures in adults are expanding. Although clavicle
      fractures in children and adolescents have traditionally been treated
      nonoperatively, surgical treatment of displaced clavicle fractures may be
      indicated for adolescent athletes. EVIDENCE ACQUISITION: A review of relevant
      articles published between 1970 and 2013 was completed using MEDLINE and the
      terms clavicle fracture and adolescent athlete. STUDY DESIGN: Clinical review.
      LEVEL OF EVIDENCE: Level 3. RESULTS: Excellent outcomes and rapid return to
      competition can be achieved with surgical management of displaced clavicle
      fractures in the adolescent athlete with high functional demands similar to those
      of their adult counterparts. Complications include hardware irritation, screw
      loosening, pin migration, peri-incisional numbness, and refracture. Athletes and
      families must be counseled regarding complications and potential need for
      secondary surgery to remove hardware. CONCLUSION: The adolescent athlete with a
      displaced, shortened, or comminuted clavicle fracture presents a unique,
      controversial dilemma for the surgeon. Earlier return to competition can be
      achieved with surgical management to restore length and alignment and may prevent
      malunion, nonunion, and poor outcomes.

PMID- 25984260
TI  - Imaging of physeal injury: overuse.
AB  - CONTEXT: As the intensity of youth participation in athletic activities continues
      to rise, the number of overuse injuries has also increased. A subset of overuse
      injuries involves the physis, which is extremely susceptible to injury. This
      paper aims to review the utility of the various imaging modalities in the
      diagnosis and management of physeal injuries in the skeletally immature
      population. EVIDENCE ACQUISITION: A search for the keywords pediatric, physis,
      growth plate, x-ray, computed tomography, magnetic resonance imaging, and overuse
      injury was performed using the PubMed database. No limits were set for the years
      of publication. Articles were reviewed for relevance with an emphasis on the
      imaging of growth plate injuries. STUDY DESIGN: Retrospective literature review.
      LEVEL OF EVIDENCE: Level 4. RESULTS: Three major imaging modalities (radiographs,
      computed tomography, and magnetic resonance imaging) complement each other in the
      evaluation of pediatric patients with overuse injuries. However, magnetic
      resonance imaging is the only modality that offers direct visualization of the
      physis, and it also offers the best soft tissue contrast for evaluating the other
      periarticular structures for concomitant injury. CONCLUSION: Imaging has an
      important role in the diagnosis of physeal injuries, and the information it
      provides has a tremendous impact on the subsequent management of these patients.

PMID- 25984261
TI  - Factors influencing ball-player impact probability in youth baseball.
AB  - BACKGROUND: Altering the weight of baseballs for youth play has been studied out
      of concern for player safety. Research has shown that decreasing the weight of
      baseballs may limit the severity of both chronic arm and collision injuries.
      Unfortunately, reducing the weight of the ball also increases its exit velocity,
      leaving pitchers and nonpitchers with less time to defend themselves. The purpose
      of this study was to examine impact probability for pitchers and nonpitchers.
      HYPOTHESIS: Reducing the available time to respond by 10% (expected from reducing
      ball weight from 142 g to 113 g) would increase impact probability for pitchers
      and nonpitchers, and players' mean simple response time would be a primary
      predictor of impact probability for all participants. STUDY DESIGN: Nineteen
      subjects between the ages of 9 and 13 years performed 3 experiments in a
      controlled laboratory setting: a simple response time test, an avoidance response
      time test, and a pitching response time test. METHODS: Each subject performed
      these tests in order. The simple reaction time test tested the subjects' mean
      simple response time, the avoidance reaction time test tested the subjects'
      ability to avoid a simulated batted ball as a fielder, and the pitching reaction
      time test tested the subjects' ability to avoid a simulated batted ball as a
      pitcher. RESULTS: Reducing the weight of a standard baseball from 142 g to 113 g
      led to a less than 5% increase in impact probability for nonpitchers. However,
      the results indicate that the impact probability for pitchers could increase by
      more than 25%. CONCLUSION: Pitching may greatly increase the amount of time
      needed to react and defend oneself from a batted ball. CLINICAL RELEVANCE: Impact
      injuries to youth baseball players may increase if a 113-g ball is used.

PMID- 25984262
TI  - Evaluation of Men's and Women's Gymnastics Injuries: A 10-Year Observational
      Study.
AB  - BACKGROUND: Injuries are common in collegiate gymnasts. Most descriptive studies
      of injury patterns in collegiate gymnasts are limited in duration or are only
      inclusive of women. HYPOTHESIS: Injury patterns in men and women differ
      significantly; women sustain a higher rate of injuries than men. STUDY DESIGN:
      Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 4. METHODS:
      Musculoskeletal and head injuries reported in the Sports Injury Monitoring System
      at a single National Collegiate Athletic Association institution for Division 1
      men's and women's gymnastics teams between 2001 and 2011 were identified. The
      variables assessed included sex, injured body part, year of eligibility, injury
      severity, surgical procedures, missed time, and team activity at the onset of
      injury. RESULTS: From 2001 to 2011, 64 male gymnasts sustained 240 injuries,
      while 55 female gymnasts sustained 201 injuries. The injury incidence was 8.78
      per 1000 athlete-exposures for men and 9.37 per 1000 athlete-exposures for women.
      Female gymnasts more commonly suffered major injuries compared with men, and more
      commonly underwent surgery after injury (24.4% of female injuries required
      surgery vs 9.2% in males). The anatomic region most often injured in men was the
      hand and wrist (24%). The anatomic region most often injured in women was the
      foot and ankle (39%). Overall, injury rates were highest in freshman-eligible
      athletes. CONCLUSION: Injury rates, overall, were similar in men and women
      gymnasts. Female gymnasts more commonly underwent surgical procedures after
      injury. Injury rates were higher in freshman-eligible athletes and decreased with
      increasing year of experience. CLINICAL RELEVANCE: Specific attention should be
      given to gymnasts transitioning into collegiate-level gymnastics; injury
      prevention strategies should focus on the ankle and foot, as well as the elbow,
      wrist, and hand.

PMID- 25984263
TI  - Unstable Surface Improves Quadriceps:Hamstring Co-contraction for Anterior
      Cruciate Ligament Injury Prevention Strategies.
AB  - BACKGROUND: Increasing quadriceps:hamstring muscular co-contraction at the knee
      may reduce the risk of anterior cruciate ligament (ACL) injury. The purpose of
      this investigation was to examine muscle activation in the quadriceps and
      hamstrings and peak kinematics of the knee, hip, and trunk when performing a
      single-leg drop (SLD) on to a Bosu ball (unstable surface) compared with on to
      the floor (stable surface). HYPOTHESES: (1) The SLD on an unstable surface would
      lower the quadriceps to hamstrings electromyographic (EMG) activation ratio (Q:H
      EMG activation ratio) compared with being performed on the floor. (2) Lower Q:H
      EMG activation ratio would be caused by a relative increase in hamstring
      activation, with no significant change in quadriceps activation. STUDY DESIGN:
      Controlled laboratory study. METHODS: Thirty-nine Division I National Collegiate
      Athletic Association (NCAA) female athletes performed 3 SLDs per leg onto a Bosu
      ball and onto the floor. Muscle activity of the vastus lateralis and lateral
      hamstrings were used to estimate peak quadriceps and hamstring activation, along
      with the Q:H EMG activation ratio. Kinematic measures at the knee, hip, and trunk
      were also estimated. Differences between landings were assessed using a 2-level
      analysis of variance (limb and surface). RESULTS: The maximum Q:H EMG activation
      ratio was significantly reduced when athletes performed an SLD onto the Bosu ball
      (20%, P < 0.001) compared with the floor. Peak hamstring activity was higher when
      athletes landed on a Bosu ball (18% higher, P = 0.029) compared with when they
      landed on the floor. CONCLUSION: Compared with landing on the floor (a stable
      surface), landing on a Bosu ball (unstable surface) changed the athlete's co
      contraction at the knee and increased hamstring activity. However, landing on a
      Bosu ball also decreased the athlete's knee flexion, which was an undesired
      effect. CLINICAL RELEVANCE: These findings highlight the potential utility of
      unstable surfaces as a training tool to reduce the risk of ACL injury in female
      athletes.

PMID- 25984264
TI  - Running habits of competitive runners during pregnancy and breastfeeding.
AB  - BACKGROUND: Running is a popular sport that may be performed safely during
      pregnancy. Few studies have characterized running behavior of competitive female
      runners during pregnancy and breastfeeding. HYPOTHESIS: Women modify their
      running behavior during pregnancy and breastfeeding. STUDY DESIGN: Observational,
      cross-sectional study. LEVEL OF EVIDENCE: Level 2. METHODS: One hundred ten
      female long-distance runners who ran competitively prior to pregnancy completed
      an online survey characterizing training attitudes and behaviors during pregnancy
      and postpartum. RESULTS: Seventy percent of runners ran some time during their
      pregnancy (or pregnancies), but only 31% ran during their third trimester. On
      average, women reduced training during pregnancy, including cutting their
      intensity to about half of their nonpregnant running effort. Only 3.9% reported
      sustaining a running injury while pregnant. Fewer than one third (29.9%) selected
      fetal health as a reason to continue running during pregnancy. Of the women who
      breastfed, 84.1% reported running during breastfeeding. Most felt that running
      had no effect on their ability to breastfeed. Women who ran during breastfeeding
      were less likely to report postpartum depression than those who did not run (6.7%
      vs 23.5%, P = 0.051), but we did not detect the same association of running
      during pregnancy (6.5% vs 15.2%, P = 0.16). CONCLUSION: Women runners reported a
      reduction in total training while pregnant, and few sustained running injuries
      during pregnancy. The effect of running on postpartum depression was not clear
      from our findings. CLINICAL RELEVANCE: We characterized running behaviors during
      pregnancy and breastfeeding in competitive runners. Most continue to run during
      pregnancy but reduce total training effort. Top reasons for running during
      pregnancy were fitness, health, and maintaining routine; the most common reason
      for not running was not feeling well. Most competitive runners run during
      breastfeeding with little perceived impact.

PMID- 25984265
TI  - Presumed testicular rupture during a college baseball game: a case report and
      review of the literature for on-field recognition and management.
AB  - Scrotal rupture during athletic competition is considered a rare occurrence;
      however, blunt trauma to the scrotum is relatively common. Protective athletic
      cups are strongly recommended for both children and adults engaging in contact
      sports as they likely limit the amount of serious injury to the scrotal contents.
      Nonetheless, should the on-field assessment by the athletic trainer, coach, or
      team physician indicate that the athlete has increased pain, ecchymosis,
      swelling, and tenderness to palpation after blunt trauma, testicular rupture
      should be suspected and prompt ultrasound and urologic assessment should be
      undertaken, as early operative intervention is necessary for testicular
      preservation. This report reviews testicular trauma during athletic competition. 

PMID- 25984267
TI  - Patterns of Utilization and Outcomes of Inpatient Psychiatric Treatment in Asian
      Americans.
AB  - Most of the knowledge of racial/ethnic disparities in mental health treatment
      utilization comes from studies examining outpatient services, and less is known
      about these disparities in inpatient services. This empirical gap may limit our
      understanding of these disparities since inpatient treatment is the most
      intensive form of specialty mental health care for patients with psychological
      disorders. We conducted a systematic chart review of 129 Asian American and 198
      White American psychiatric inpatients to examine patterns of inpatient
      psychiatric treatment utilization. Demographic and clinical data were extracted
      from admission and discharge records during a two-year timeframe. Patterns of
      diagnoses revealed that Asian American patients utilized inpatient services for
      more severe psychiatric diagnoses compared to White American patients. Despite
      this, there were no racial/ethnic differences in levels of functional impairment
      at admission, and there were no racial/ethnic differences in length of treatment
      stay. For Asian American patients, level of psychosocial functioning at admission
      predicted length of stay. A better understanding of patterns of inpatient
      treatment use is needed to meet the clinical needs of Asian Americans with
      psychiatric disorders.

PMID- 25984268
TI  - Label-free Detection of Protein Released during Platelet Activation by CNT
      Enhanced Love Mode SAW Sensors.
AB  - Platelet-rich plasma (PRP) has been applied in a series of clinical treatments.
      PRP contains high-concentrated platelets, which, when activated, could secret a
      variety of growth factors and cytokines, to promote and/or enhance healing of
      injured tissues. Non-activated platelets suspension could be prepared by an
      isolation method of centrifugation and washing currently. However, it is not
      clear whether platelets, if any, are already activated during this process and
      there is no simple method to monitor their activation accordingly. Shear
      Horizontal Surface Acoustic Wave sensors (SH-SAW, Love Mode) are promising in
      fundamental biology as well as biomedical engineering, detecting cell behaviors
      in liquid in a non-invasive, simple and quantitative manner. In this study, Love
      mode sensors are adopted for the label-free detection of protein secreted by
      platelets. Carbon nanotube (CNT) is reported as an advisable platform of both non
      specific protein adsorption and specific protein binding. For further improvement
      of Love mode sensor performance, novel CNT -coated parylene-C film is prepared on
      its surface as both the acoustic-wave-guiding layer and bio-interface layer. The
      S21 loss curves of Love mode sensors were recorded and the corresponding
      resonance frequencies were extracted. The results showed that the CNT-enhanced
      sensor possessed an increased resonance frequency shift when compared to normal
      sensor with single parylene-C film under identical collagen concentrations. Then,
      the modified sensor is used for label-free detection of protein released by
      various concentrations of platelets. The results revealed high sensitivity and
      consistency, indicating the potential of CNT-enhanced Love mode sensors in cell
      based applications.

PMID- 25984269
TI  - Parallel and Multivalued Logic by the Two-Dimensional Photon-Echo Response of a
      Rhodamine-DNA Complex.
AB  - Implementing parallel and multivalued logic operations at the molecular scale has
      the potential to improve the miniaturization and efficiency of a new generation
      of nanoscale computing devices. Two-dimensional photon-echo spectroscopy is
      capable of resolving dynamical pathways on electronic and vibrational molecular
      states. We experimentally demonstrate the implementation of molecular decision
      trees, logic operations where all possible values of inputs are processed in
      parallel and the outputs are read simultaneously, by probing the laser-induced
      dynamics of populations and coherences in a rhodamine dye mounted on a short DNA
      duplex. The inputs are provided by the bilinear interactions between the molecule
      and the laser pulses, and the output values are read from the two-dimensional
      molecular response at specific frequencies. Our results highlights how ultrafast
      dynamics between multiple molecular states induced by light-matter interactions
      can be used as an advantage for performing complex logic operations in parallel,
      operations that are faster than electrical switching.

PMID- 25984270
TI  - DELETED TEXT IN A MANUSCRIPT. GALEN ON THE EYE AND THE MARC. GR. 276.

PMID- 25984271
TI  - Serum Matrix Metalloproteinase-7 is an independent prognostic biomarker in
      advanced bladder cancer.
AB  - BACKGROUND: Urine markers have been studied extensively but there is a lack of
      blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells
      and by tumor cells and is overexpressed in a variety of epithelial and
      mesenchymal tumors. In this study, we assessed with an immunoassay we developed,
      the prognostic value of serum MMP-7 in a series of patients with advanced bladder
      cancer. METHODS: Serum samples were collected from 56 patients with advanced
      bladder cancer who were treated at the Montpellier Cancer Institute between March
      2003 and December 2004. MMP-7 was quantified in serum samples by using a
      homogeneous sandwich fluoroimmunoassay we developed based on the time resolved
      amplified cryptate emission (TRACE) technology. RESULTS: The median overall
      survival of the study population was 2.2 years (95% CI, 1.4 to 3.0) with 1- and 5
      year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%),
      respectively. High MMP-7 serum levels were associated with poor survival. Using a
      cut-off value of 11.5 ng/mL, the median overall survival was 3.0 years (95% CI,
      1.5 to 5.1) for patients with MMP-7 serum level <11.5 ng/mL and 1.3 years (95%
      CI, 0.8 to 2.5) for patients with serum level ?11.5 ng/mL. Multivariate analysis
      identified high MMP-7 serum concentration as an independent prognostic factor for
      survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4).
      CONCLUSIONS: Our results show that the MMP-7 serum concentration is an
      independent prognostic factor in patients with locally advanced and or metastatic
      bladder cancer.

PMID- 25984273
TI  - Addressing challenges of training a new generation of clinician-innovators
      through an interdisciplinary medical technology design program: Bench-to-Bedside.
AB  - Graduate medical education has traditionally focused on training future
      physicians to be outstanding clinicians with basic and clinical science research
      skills. This focus has resulted in substantial knowledge gains, but a modest
      return on investment based on direct improvements in clinical care. In today's
      shifting healthcare landscape, a number of important challenges must be overcome
      to not only improve the delivery of healthcare, but to prepare future physicians
      to think outside the box, focus on and create healthcare innovations, and
      navigate the complex legal, business and regulatory hurdles of bringing
      innovation to the bedside. We created an interdisciplinary and experiential
      medical technology design competition to address these challenges and train
      medical students interested in moving new and innovative clinical solutions to
      the forefront of medicine. Medical students were partnered with business, law,
      design and engineering students to form interdisciplinary teams focused on
      developing solutions to unmet clinical needs. Over the course of six months teams
      were provided access to clinical and industry mentors, $500 prototyping funds,
      development facilities, and non-mandatory didactic lectures in ideation, design,
      intellectual property, FDA regulatory requirements, prototyping, market analysis,
      business plan development and capital acquisition. After four years of
      implementation, the program has supported 396 participants, seen the development
      of 91 novel medical devices, and launched the formation of 24 new companies. From
      our perspective, medical education programs that develop innovation training
      programs and shift incentives from purely traditional basic and clinical science
      research to also include high-risk innovation will see increased student
      engagement in improving healthcare delivery and an increase in the quality and
      quantity of innovative solutions to medical problems being brought to market. 

PMID- 25984272
TI  - Gene expression profiling of immunomagnetically separated cells directly from
      stabilized whole blood for multicenter clinical trials.
AB  - BACKGROUND: Clinically useful biomarkers for patient stratification and
      monitoring of disease progression and drug response are in big demand in drug
      development and for addressing potential safety concerns. Many diseases influence
      the frequency and phenotype of cells found in the peripheral blood and the
      transcriptome of blood cells. Changes in cell type composition influence whole
      blood gene expression analysis results and thus the discovery of true transcript
      level changes remains a challenge. We propose a robust and reproducible
      procedure, which includes whole transcriptome gene expression profiling of major
      subsets of immune cell cells directly sorted from whole blood. METHODS: Target
      cells were enriched using magnetic microbeads and an autoMACS(r) Pro Separator
      (Miltenyi Biotec). Flow cytometric analysis for purity was performed before and
      after magnetic cell sorting. Total RNA was hybridized on HGU133 Plus 2.0
      expression microarrays (Affymetrix, USA). CEL files signal intensity values were
      condensed using RMA and a custom CDF file (EntrezGene-based). RESULTS: Positive
      selection by use of MACS(r) Technology coupled to transcriptomics was assessed
      for eight different peripheral blood cell types, CD14+ monocytes, CD3+, CD4+, or
      CD8+ T cells, CD15+ granulocytes, CD19+ B cells, CD56+ NK cells, and CD45+ pan
      leukocytes. RNA quality from enriched cells was above a RIN of eight. GeneChip
      analysis confirmed cell type specific transcriptome profiles. Storing whole blood
      collected in an EDTA Vacutainer(r) tube at 4 degrees C followed by MACS does not
      activate sorted cells. Gene expression analysis supports cell enrichment
      measurements by MACS. CONCLUSIONS: The proposed workflow generates reproducible
      cell-type specific transcriptome data which can be translated to clinical
      settings and used to identify clinically relevant gene expression biomarkers from
      whole blood samples. This procedure enables the integration of transcriptomics of
      relevant immune cell subsets sorted directly from whole blood in clinical trial
      protocols.

PMID- 25984274
TI  - Analysis of Gap in Service Quality in Drug Addiction Treatment Centers of Kerman,
      Iran, Using SERVQUAL Model.
AB  - BACKGROUND: Treatment of drug addicts is one of the main strategies of drug
      control in Iran. Client satisfaction strongly influences the success of any
      treatment program. This study aimed to explore the difference between customer
      expectations and perceptions in drug addiction treatment centers of Kerman, Iran,
      using SERVQUAL model. METHODS: Using a cross-sectional design 260 clients
      referring to drug addiction treatment centers of Kerman, were enrolled in 2012.
      From among 84 clinics, 20 centers were selected randomly. Based on the number of
      clients registered in each center, a random sample proportional to the size was
      selected and 290 subjects were invited for interviews. A well validated 22-item
      questionnaire, which measured the 5 dimensions of service quality (reliability,
      assurance, tangibility, empathy, and responsiveness), was completed by
      participants. Each item measured 2 aspects of service quality; expectations and
      perceptions. FINDINGS: Mean +/- SD (Standard deviation) age of the subjects was
      37.7 +/- 9.4. Most of them were male (87.7%). Less than half of them had an
      educational level lower than diploma. The total score of clients' expectations
      was higher than their perceptions (P < 0.001). Considering the 5 dimensions of
      the SERVQUAL model, only 1 dimension (i.e., assurance) showed no difference
      between perceptions and expectations of the participants (P = 0.134). CONCLUSION:
      There was a gap between the clients' expectations and what they actually
      perceived in the clinics. Thus, more attention should be devoted to the clients'
      views regarding service quality in addiction treatment clinics.

PMID- 25984275
TI  - The Relationship between Mental Health and Addiction to Mobile Phones among
      University Students of Shahrekord, Iran.
AB  - BACKGROUND: The risk of cell phone addiction is a social and psychological
      problem which has been proposed by psychologists, psychiatrists, and educational
      supervisors. The present study aimed to investigate the behavior of mobile phone
      addicts and mental health of university students of Shahrekord, Iran. METHODS:
      This study was an applied research survey for the purposes of this study. The
      study population yconsisted of all the students of Payame Noor University,
      Islamic Azad University, and University of Medical Sciences. The study population
      consisted of 296 students who were randomly selected from the target population.
      To collect data, two types of questionnaires were used, the Symptom Checklist-90
      R(SCL-90-R) questionnaire, and the 32-point scale questionnaire of behavior
      associated with ymobile phone use (Hooper and Zhou, 2007). Data analysis was
      performed using SPSS software, statistical analysis, frequency distribution,
      mean, one-way ANOVA, chi-square, and LSD (Least significance difference).
      FINDINGS: The results showed that university students of Shahrekord, based on the
      six categories of mobile yaddiction behaviors, were mostly placed in habitual
      behaviors (21.49%), addiction (21.49%), and intentional (21.49%) categories. By
      reviewing mental health indicators, it was found that students were affected with
      depressive disorder (17.30%), obsessive compulsive disorder (14.20%), and
      interpersonal sensitivity (13.80%). The results showed that there was a
      significant inverse relationship ybetween mental health and habitual behaviors (r
      = -0.417), dependence (r = -0.317), addiction (r = -0.330), and incontinence (r =
      -0.309) in using mobile phone (P < 0.001). CONCLUSION: Survey results showed that
      with increased and improved mental health, the student's rate of cell phone
      addiction reduced.

PMID- 25984276
TI  - Does ingestion of tincture of opium notably raise blood alcohol concentration?
AB  - BACKGROUND: Tincture of opium (TOP) is currently used for maintenance therapy in
      treatment of opioids addiction. It contains ethanol. The present study was
      conducted to assess the increase in blood alcohol concentration (BAC) in its
      users; a process which may interfere with breath-alcohol test performed by law
      enforcement or traffic police. METHODS: A total of 143 individuals were selected
      randomly from drug users who had been referred to an addiction treatment clinic.
      They were asked to undergo breath-alcohol test 15, 30, 45, and 60 min after
      taking their daily dosage of TOP. The resulting figures were statistically
      analyzed by t-test and chi-square test using SPSS for Windows. FINDINGS: The
      calculated blood ethanol concentration rose to 26.33 +/- 14.34, 29.15 +/- 6.70,
      and 33.03 +/- 8.46 in persons taking 20, 25, and 30 ml TOP respectively, 5 min
      after their drug ingestion. The figures turned into zero after 15 min.
      CONCLUSION: Users of TOP should be reassured about its alcoholic content. Its
      alcoholic content cannot produce equilibrium disturbance or notable BAC. However,
      it is recommended that users of TOP are observed in addiction treatment centers
      for 15 min after taking their drug to reach a higher degree of certainty about
      any effect of alcoholic content of TOP.

PMID- 25984277
TI  - A study of the phenomenology of psychosis induced by methamphetamine: a
      preliminary research.
AB  - BACKGROUND: Psychotic disorder due to industrial drug, such as methamphetamine
      addiction, is one of the important causes for referral to psychiatric hospital.
      Psychotic symptoms in these patients are varied. A group of researchers believe
      that methamphetamine-induced psychosis is completely similar to schizophrenia.
      Others believe that at least some cases of permanent psychotic clinical
      manifestation due to methamphetamine abuse are different from schizophrenia. In
      the present study, the existence of differences between psychotic symptoms caused
      by methamphetamine addiction and schizophrenia is investigated. METHODS: This
      study was a qualitative study. Patients with psychosis due to methamphetamine
      addiction were selected from among patients who were hospitalized in hospitals of
      the Kerman University of Medical Sciences, Iran. All patients were interviewed
      using unstructured interview based on self- reporting. Interviews were recorded
      and reviewed later. FINDINGS: Based on clinical observations, some of the
      patients with psychotic disorder due to methamphetamine showed rare symptoms that
      had been mostly reported in psychosis due to organic disorders and some of them
      showed symptoms that had not been reported before. CONCLUSION: This study showed
      that in a group of patients with methamphetamine-induced psychosis, clinical
      manifestation is different from schizophrenia.

PMID- 25984278
TI  - The Synergistic (MARATHON) Effect of Combined Methamphetamine with Sexual
      Stimulant Drugs on Increasing the Likelihood of High-Risk Sexual Behaviors.
AB  - BACKGROUND: Chronic drug abuse and sexual dysfunction specifically erectile
      dysfunction may lead drug abusers to seek over-the-counter or non-prescription
      medications, out of which Sildenafil citrate, sold as the trade name of Viagra(r)
      can be considered as a prime and important treatment. Therefore, the research
      purpose was to draw a comparison and review the role of methamphetamine abuse and
      sildenafil use in increasing the likelihood of high-risk sexual behaviors (both
      concomitant and non-concomitant use). METHODS: Hence, a total of 40 patients
      diagnosed with methamphetamine abuse were recruited through the administration of
      structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of
      Mental Disorders, 4th Edition), through purposive sampling and subsequent to
      being qualified in accordance with the selection criteria by psychologists and
      general practitioners. All the 40 drug abusers (20 methamphetamine abusers with
      concomitant use of Aphrodisiac drugs (sexual stimulant pills) and 20
      methamphetamine abusers) described their sexual risk behaviors subsequent to the
      drug use. FINDINGS: Supported the between-group difference that is to say that,
      the group with concomitant methamphetamine abuse differed significantly in all
      the items when compared with the control group. However, this group scored lower
      on the item of sexual intercourse with drug addicted prostitutes using condom and
      both groups demonstrated high pick on this item. CONCLUSION: Overall, the
      concomitant methamphetamine chronic abuse with sexual stimulant drugs generates
      Aphrodisiac drugs impulses and is found to be related to higher frequencies of
      sexual risk behaviors and sexual intercourse with addicted prostitutes.

PMID- 25984279
TI  - Serum level of plasminogen activator inhibitor type-1 in addicted patients with
      coronary artery disease.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein with
      inhibitory effects on the formation of plasmin from plasminogen by plasminogen
      activator. Thus, it prevents clot lysis in vessel walls. Several evidences prove
      the relationship between coronary artery disease and response to fibrinolytic
      therapy in patients with myocardial infarction (MI) with PAI-1 level. Opium
      addiction is one of the most important factors in causing MI and cardiovascular
      events. This is due to it causing imbalance between coagulation and
      anticoagulation factors in the blood. This study was designed and implemented to
      determine the levels of PAI-I in opium-addicted patients with coronary artery
      disease in comparison with non addicts. METHODS: In this case-control study, 160
      patients with coronary heart disease (CHD), which was confirmed by angiography
      results, were enrolled. All of the patients had a medical history, their
      creatinine levels and lipid profile were evaluated, morphine urine test was
      performed, and after that a blood sample was taken to determine the levels of PAI
      1. Thus, the 80 patients who had a positive morphine urine test result formed the
      case group, and the control group was constituted of the 80 patients with
      negative morphine test results. The two groups were matched. FINDINGS: Average
      level of PAI-1 in the control group was 2.4 +/- 2.6 and in the case group was 8.8
      +/- 9.1 and it was statistically significant (P < 0.001). The frequency of two
      vessel disease was higher in opium addicted patients than non-addicted patients
      and this was statistically significant (P = 0.030). However, the frequency of
      single vessel and three vessel disease was the same in the two groups. The two
      groups had no differences in age, lipid profile, and creatinine level. Moreover,
      females are at a higher risk of high PAI-1 levels. CONCLUSION: PAI-1 levels in
      opium addicted patients with CHD are higher than other patients. In these
      patients, the risk of atherosclerosis and MI is higher than normal.

PMID- 25984280
TI  - One decade "narcotic addicted patients with deep vein thrombosis" in st. Alzahra
      hospital of isfahan, iran.
AB  - BACKGROUND: Behavior and substance addiction is one of the risk factors for deep
      vein thrombosis (DVT). The aim of this study investigating the relationship
      between the different clinical manifestations pattern of DVT with the way, the
      amount and duration of narcotic drugs in patients admitted to St. Alzahra
      Hospital in Isfahan, Iran, during 10 years. METHODS: In a cross-sectional study
      we studied all of the patients with DVT in St. Alzahra Hospital since 2003-2013
      were studied. FINDINGS: A total of 238 (59.1%) of the patients were male and 165
      (40.9%) female. The mean age of men and women were 18.80 +/- 48 and 19.60 +/-
      3.48 years old. The mean length of staying in the hospital was 5.40 +/- 7.20
      days. Addiction among patients with DVT was 19.1%. 28.2% of men suffered from DVT
      and 6% of the women were drug addicts (P < 0.001). Among the 77 patients taking
      the drug, 53.2% were heroin, 35.1%opium, and 11.7% used other injectable drugs.
      The results showed that 19 patients (28.6%) were taking the drug once daily,
      27.3% twice a day, 6.5% three times a day, 15.6% once a week, and 26% taking the
      drug twice a week. From 403 patients, 2.2% had a problem in the upper limb, 44.4%
      in the left hand, and 55.6 in the right hand. The results showed that none of the
      77 studied patients had involvement of upper limbs, but all of them in the lower
      limb. About 11.2% of studied patients were addicted to injective drugs. Also, 6%
      were addicted to non-injectable drugs and 2% to both injectable and non
      injectable drugs. CONCLUSION: DVT has many risk factors and addiction and
      intravenously (IV) drug abuse one of the most important for this illness and this
      problem mast be noticed by health worker and physicians.

PMID- 25984281
TI  - Changes in serum biochemical factors associated with opium addiction after
      addiction desertion.
AB  - BACKGROUND: The long time use of opium has some effects on serums biochemical
      factors, the determination of this variation is a new approach in understanding
      off addiction and relive of drug abuser health. Hence in this study, these
      indicators in person who were withdrawing of opium have been studied. METHODS: In
      this cross-sectional study bloods biochemical factors such as fasting blood sugar
      (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN),
      creatinine, cholesterol, total protein, and fibrinogen in three groups serum were
      studied: (1) Who had been permanent opium users more than 2 years (case). (2)
      Dependent person who has taken one month addiction withdrawal course (control).
      (3) A healthy group that had been demographically similar to the other groups.
      FINDINGS: According to these study findings, FBS serum level in the case group is
      lower than control group. Serum level of Na, creatinine, and blood triglyceride
      (TG) in case study are higher than group control. Concentration of potassium, Ca,
      UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case
      study and group control showed no significant difference. Also, in withdrawing
      case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase
      and thrombin time decrease. CONCLUSION: According to this study not only the
      longtime use of opium but also opium with drawerin opium dependent people can
      change their serum biochemical factors. So recognition, treatment, and prevention
      of this change could be a new step in improving of health and condition of
      patients.

PMID- 25984283
TI  - Impact of smoking on speed and coordination of upper limb movement.
AB  - BACKGROUND: The purpose of this study was to determine the effect of smoking on
      speed and coordination of upper-limb movement. METHODS: A total of 62 healthy,
      young individuals were randomly selected for participation in this study. Out of
      total subjects, 31 were smokers with a mean age 20.84 years and 31 were non
      smokers with a mean age 19.97 years and placed in group A and group B,
      respectively. Plate taping test was administered to all the subjects to determine
      their speed and coordination of upper limb. FINDINGS: Student's t-test was
      applied between both groups to see the difference in their plate taping test's
      time; its t-value was 5.03. CONCLUSION: Statistical significant difference was
      seen between both the groups in the result of plate taping test, which suggests
      that smoking can affect the speed and coordination of upper limb in a negative
      way and cause its deterioration. Therefore, immediate quitting from smoking is of
      high value and requirements to have a good speed and coordination of upper-limb
      movements.

PMID- 25984282
TI  - Current research on methamphetamine: epidemiology, medical and psychiatric
      effects, treatment, and harm reduction efforts.
AB  - BACKGROUND: Methamphetamine (MA) which is known as "shisheh" in Iran is a drug
      that widely is used in many parts of the world and it is near to a decade that is
      available for the most drug users and has a considerable prevalence of use. Due
      to high abuse prevalence and very new challenging phenomenon, it is very
      important that researchers and treatment providers become more familiar with
      different aspects of MA. DISCUSSION: It has multiple neurobiological impacts on
      the nervous system, some of which are transitory and some longer lasting. MA
      activates the reward system of the brain and produces effects that are highly
      reinforcing, which can lead to abuse and dependence. Routes of administration
      that produce rapid onset of the drug's effects (i.e., smoking and injection) are
      likely to lead to more rapid addiction and more medical and psychiatric effects.
      No effective pharmacotherapies have been developed for the treatment of MA
      dependence; although, this is an area of very active research. Several behavioral
      treatments have been shown to reduce MA use, but better treatments are needed.
      CONCLUSION: Harm reduction strategies for non-treatment seeking MA users are
      needed to reduce the risk of human immunodeficiency virus and other medical
      risks. The research agenda for MA is substantial, with development of effective
      pharmacotherapies as one of the most important priorities. Appropriate and
      effective response for prevention, treatment and harm reduction services due to
      increasing problems regarding MA in Iran and some other countries in the region.

PMID- 25984285
TI  - Smoking Addiction among Dental Students of Central India.

PMID- 25984284
TI  - Persistent psychosis after abuse of high dose of zolpidem.
AB  - BACKGROUND: Zolpidem is a non-benzodiazepine medication which selectively affects
      GABA A receptors and treats insomnia. There are numerous reports of psychosis
      following the consumption of zolpidem all of which recovered after stopping the
      medication. CASE REPORT: A 27 year old male law student, who was treated with 10
      mg zolpidem due to insomnia, increased the dosage to 500 mg during 3 months. Not
      only was his insomnia remained untreated, but also he gradually became isolated,
      suspicious, and aggressive, and dropped out of university. He was then
      hospitalized in a psychiatric ward for 2 months, and was treated with
      antipsychotics and gradual discontinuation of zolpidem. With no improvement in
      psychosis and sleep improvement he was discharged. After two weeks he was
      hospitalized again and went under electroconvulsive therapy (ECT) and
      antipsychotic therapy, and was discharged with relative improvement. Now, after
      three years, he is diagnosed with schizophrenia and with modest improvements he
      is under care and treatment. CONCLUSION: Zolpidem is a fairly useful medication
      for treating sleep problems, especially improving beginning of sleep. However,
      physicians yand clinicians should consider the conditions, predispositions, and
      personal and family history of types of psychosis, alcohol and drug abuse in the
      comprehensive assessment and treatment plan for patients with insomnia.

PMID- 25984286
TI  - Socioeconomic Status and in-hospital Mortality of Acute Coronary Syndrome: Can
      Education and Occupation Serve as Preventive Measures?
AB  - BACKGROUND: Socioeconomic status (SES) can greatly affect the clinical outcome of
      medical problems. We sought to assess the in-hospital mortality of patients with
      the acute coronary syndrome (ACS) according to their SES. METHODS: All patients
      admitted to Tehran Heart Center due to 1(st)-time ACS between March 2004 and
      August 2011 were assessed. The patients who were illiterate/lowly educated (<=5
      years attained education) and were unemployed were considered low-SES patients
      and those who were employed and had high educational levels (>5 years attained
      education) were regarded as high-SES patients. Demographic, clinical,
      paraclinical, and in-hospital medical progress data were recorded. Death during
      the course of hospitalization was considered the end point, and the impact of SES
      on in-hospital mortality was evaluated. RESULTS: A total of 6246 hospitalized
      patients (3290 low SES and 2956 high SES) were included (mean age = 60.3 +/- 12.1
      years, male = 2772 [44.4%]). Among them, 79 (1.26%) patients died. Univariable
      analysis showed a significantly higher mortality rate in the low-SES group (1.9%
      vs. 0.6%; P < 0.001). After adjustment for possible cofounders, SES still showed
      a significant effect on the in-hospital mortality of the ACS patients in that the
      high-SES patients had a lower in-hospital mortality rate (odds ratio: 0.304, 95%
      confidence interval: 0.094-0.980; P = 0.046). CONCLUSIONS: This study found that
      patients with low SES were at a higher risk of in-hospital mortality due to the
      ACS. Furthermore, the results suggest the need for increased availability of jobs
      as well as improved levels of education as preventive measures to curb the
      unfolding deaths owing to coronary artery syndrome.

PMID- 25984287
TI  - Mobile phone-based education and counseling to reduce stress among patients with
      diabetes mellitus attending a tertiary care hospital of India.
AB  - BACKGROUND: Stress among diabetic patients is much more as compared to normal
      individuals. A delayed recognition of stress undoubtedly worsens the prognosis
      for survival for many diabetic patients. Hence, this study was planned to develop
      an intervention model for the reduction of stress among diabetic patients and to
      evaluate the developed intervention model in the proposed group. METHODS: This
      study was conducted in endocrinology outpatient department of a tertiary care
      hospital. Starting at random, the patients were allocated to control group and
      test group. Controls were given printed educational materials. Test group were
      counseled with intense lifestyle education using both printed materials and
      computers; they were contacted by telephones by the investigator every 3 weeks
      for 3 months and SMS were sent every week containing some educational tips.
      RESULTS: Mean age was 54 +/- 11.5 years overall ranging from 30 years to 80
      years. About two-third of participants were males with similar distribution in
      both the groups (intervention = 66%, control = 64%). Half (50%) of the
      participants lived in joint families, followed by nuclear families (40%). Most
      (83%) were married and with either graduate or above graduate education (n =
      39%). No significant difference was observed in socio-demographic characteristics
      among both control and intervention groups (P > 0.05). The average stress scores
      were similar (18.9) at baseline for control and intervention arms. At 3-month
      follow-up, however, these scores reduced to 17.05 in the intervention arm while
      they increased to 20.7 in the control arm. At 3 months follow-up, higher
      proportion of stress reduction was seen in the intervention group. CONCLUSIONS:
      Intervention in the form of intensive lifestyle education and phone calls and SMS
      significantly decrease their stress score. Mobile-based education has great
      potential to improve their mental status and increase patient-provider
      communication, and to decrease stress.

PMID- 25984288
TI  - Modes of Alphabet Letter Production during Middle Childhood and Adolescence:
      Interrelationships with Each Other and Other Writing Skills.
AB  - Although handwriting is typically taught during early childhood and keyboarding
      may not be taught explicitly, both may be relevant to writing development in the
      later grades. Thus, Study 1 investigated automatic production of the ordered
      alphabet from memory for manuscript (unjoined), cursive (joined), and keyboard
      letter modes (alphabet 15 sec) and their relationships with each other and
      spelling and composing in typically developing writers in grades 4 to 7 (N =
      113). Study 2 compared students with dysgraphia (impaired handwriting, n=27),
      dyslexia (impaired word spelling, n=40), or oral and written language learning
      disability (OWL LD) (impaired syntax composing, n=11) or controls without
      specific writing disabilities (n=10) in grades 4 to 9 (N=88) on the same alphabet
      15 modes, manner of copying (best or fast), spelling, and sentence composing. In
      Study 1, sequential multilevel model regressions of predictor alphabet 15 letter
      production/selection modes on spelling and composition outcomes, measured
      annually from grade 4 to grade 7 (ages 9 to 13 years), showed that only the
      cursive mode uniquely, positively, and consistently predicted both spelling and
      composing in each grade. For composing, in grade 4 manuscript mode was positively
      predictive and in grades 5-7 keyboard selection was. In Study 2 all letter
      production modes correlated with each other and one's best and fast sentence
      copying, spelling, and timed sentence composing. The groups with specific writing
      disabilities differed from control group on alphabet 15 manuscript mode, copy
      fast, and timed sentence composing. The dysgraphia and dyslexia groups differed
      on copying sentences in one's best handwriting, with the dysgraphia group scoring
      lower. The educational and theoretical significance of the findings are discussed
      for multiple modes and manners of letter production/selection of the alphabet
      that support spelling and composing beyond the early grades in students with and
      without specific writing disabilities.

PMID- 25984289
TI  - The prevalence of vascular calcification in patients with end-stage renal disease
      on hemodialysis: a cross-sectional observational study.
AB  - BACKGROUND: This multicenter international cross-sectional observational study
      characterized vascular and valvular calcification burden and correlations with
      pulse pressure, diabetes, hypertension, and cardiovascular diseases in prevalent
      hemodialysis patients. METHODS: We enrolled 275 consecutive adults with end-stage
      renal disease on maintenance hemodialysis for ?3 months. Coprimary endpoints were
      prevalences of: (1) echocardiographic calcification in mitral valve, aortic valve
      or mitral annulus; (2) aortoiliac tree vascular calcifications by plain lateral
      lumbar X-ray. Correlations among calcification sites and with demographics and
      comorbidities were determined. Pulse pressures were determined. RESULTS:
      Subjects' mean +/- standard deviation (SD) age was 56 +/- 15.9 years; mean (SD)
      dialysis duration was 4.5 +/- 4.3 years. Overall, 100% of echocardiographically
      imaged patients (n = 243) had calcification in aortic valve, mitral valve, or
      mitral annulus; 77.8% of X-rayed patients (n = 248) had abdominal aortic
      calcification. Radiographic abdominal aortic calcification score correlated
      significantly with calcification of aortic valve (p < 0.0001) and mitral annulus
      (p = 0.0001) but not mitral valve. Aortic valve, mitral valve, and mitral annulus
      calcification correlated significantly among themselves (p < 0.0001).
      Moderate/severe aortic valve calcification was significantly more prevalent in
      patients aged ?65 years than <65 years, men than women, and Whites than African
      Americans. Pulse pressure correlated significantly with vascular calcification
      score (p = 0.0049) but not with valvular calcification at any site. CONCLUSIONS:
      Vascular and valvular calcification are highly prevalent in the hemodialysis
      population. Peripheral vascular calcification correlates significantly with
      elevated pulse pressure and can be assessed easily using lateral lumbar X-ray.
      Further studies investigating the interaction between pulse pressure and
      development or progression of vascular calcification are of interest.

PMID- 25984290
TI  - In vivo volumetric depth-resolved vasculature imaging of human limbus and sclera
      with 1MUm swept source phase-variance optical coherence angiography.
AB  - We present nnnnnin vivo volumetric depth-resolved vasculature images of the
      anterior segment of the human eye acquired with phase-variance based motion
      contrast using a high-speed (100 kHz, 105 A-scans/s) swept source optical
      coherence tomography system (SSOCT). High phase stability SSOCT imaging was
      achieved by using a computationally efficient phase stabilization approach. The
      human corneo-scleral junction and sclera were imaged with swept source phase
      variance optical coherence angiography and compared with slit lamp images from
      the same eyes of normal subjects. Different features of the rich vascular system
      in the conjunctiva and episclera were visualized and described. This system can
      be used as a potential tool for ophthalmological research to determine changes in
      the outflow system, which may be helpful for identification of abnormalities that
      lead to glaucoma.

PMID- 25984291
TI  - Sex-specific and developmental expression of Dmrt genes in the starlet sea
      anemone, Nematostella vectensis.
AB  - BACKGROUND: The molecular mechanisms underlying sex determination and
      differentiation in animals are incredibly diverse. The Dmrt (doublesex and mab-3
      related transcription factor) gene family is an evolutionary ancient group of
      transcription factors dating to the ancestor of metazoans that are, in part,
      involved in sex determination and differentiation in numerous bilaterian animals
      and thus represents a potentially conserved mechanism for differentiating males
      and females dating to the protostome-deuterostome ancestor. Recently, the
      diversity of this gene family throughout animals has been described, but the
      expression and potential function for Dmrt genes is not well understood outside
      the bilaterians. RESULTS: Here, we report sex- and developmental-specific
      expression of all 11 Dmrts in the starlet sea anemone Nematostella vectensis.
      Nine out of the eleven Dmrts showed significant differences in developmental
      expression, with the highest expression typically in the adult stage and, in some
      cases, with little or no expression measured during embryogenesis. When
      expression was compared in females and males, seven of the eleven Dmrt genes had
      significant differences in expression with higher expression in males than in
      females for six of the genes. Lastly, expressions of two Dmrt genes with
      differential expression in each sex are located in the mesenteries and into the
      pharynx in polyps. CONCLUSIONS: Our results show that the phylogenetic diversity
      of Dmrt genes in N. vectensis is matched by an equally diverse pattern of
      expression during development and in each sex. This dynamic expression suggests
      multiple functions for Dmrt genes likely present in early diverging metazoans.
      Detailed functional analyses of individual genes will inform hypotheses regarding
      the antiquity of function for these transcription factors.

PMID- 25984293
TI  - Using The Descending Aortic Wall Thickness Measured In Transesophageal
      Echocardiography As A Risk Marker For Aortic Dissection.
AB  - OBJECTIVE: The aim of this study is to estimate whether aortic wall thickness is
      increased in patients with Aortic dissection (AD) compared to low risk control
      group and can be used in addition to aortic diameter as a risk marker of AD.
      BACKGROUND: AD occurs due to pathologies that may increase thickness of the
      aortic wall. Transesophageal echocardiography (TEE) has the ability to visualize
      both the thoracic aortic wall and lumen. Aortic diameter has been used to predict
      aortic dissection and timing of surgery, but it is not always predictive of that
      risk. METHODS: In 48 patients with AD who underwent TEE were examined
      retrospectively and compared to 48 control patients with patent foramen ovale
      (PFO). We measured aortic diameter at different levels, intimal/medial thickness
      (IMT) and complete wall thickness (CMT). Demographic data and cardiovascular risk
      factors were reviewed. The data was analyzed using ANOVA and student t test.
      RESULTS: (AD) patients were older [mean age 66 AD vs. 51 PFO], had more
      hypertension, diabetes, hyperlipidemia and Coronary artery disease. Both IMT and
      CMT in the descending aorta were increased in AD group [(1.85 vs. 1.43 mm; P=0.03
      and 2.93 vs. 2.46 mm; p=0.01). As expected the diameter of ascending aorta was
      also greater in AD (4.61 vs. 2.92 cm; P=0.004). CONCLUSIONS: CMT and IMT in the
      descending aorta detected by TEE is greater in patients with AD when compared to
      control and may add prognostic data to that of aortic diameter.

PMID- 25984294
TI  - Personal needs versus national needs: public attitudes regarding health care
      priorities at the personal and national levels.
AB  - BACKGROUND: Many stakeholders have little or no confidence in the ability of the
      public to express their opinions on health policy issues. The claim often arises
      that lay people prioritize according to their own personal experiences and may
      lack the broad perspective necessary to understand the needs of the population at
      large. In order to test this claim empirically, this study compares the public's
      priorities regarding personal insurance to their priorities regarding allocation
      of national health resources. Thus, the study should shed light on the extent to
      which the public's priorities at the national level are a reflection of their
      priorities at the personal level. METHODS: A telephone survey was conducted with
      a representative sample of the Israeli adult population aged 18 and over (n =
      1,225). The public's priorities were assessed by asking interviewees to assume
      that they were the Minister of Health and from this point of view allocate an
      additional budget among various health areas. Their priorities at the personal
      level were assessed by asking interviewees to choose preferred items for
      inclusion in their personal supplementary health insurance. RESULTS: Over half of
      the respondents (54%) expressed different personal and national priorities. In
      multivariable logistic analysis, "population group" was the only variable found
      to be statistically significant; Jews were 1.8 times more likely than Arabs to
      give a similar response to both questions. Income level was of borderline
      significance. CONCLUSIONS: At least half of the population was able to
      differentiate between their personal needs and national policy needs. We do not
      advocate a decision-making process based on polls or referendums. However, we
      believe that people should be allowed to express their priorities regarding
      national policy issues, and that decision-makers should consider these as one of
      the factors used to determine policy decisions.

PMID- 25984292
TI  - Evolution of retinoic acid receptors in chordates: insights from three lamprey
      species, Lampetra fluviatilis, Petromyzon marinus, and Lethenteron japonicum.
AB  - BACKGROUND: Retinoic acid (RA) signaling controls many developmental processes in
      chordates, from early axis specification to late organogenesis. The functions of
      RA are chiefly mediated by a subfamily of nuclear hormone receptors, the retinoic
      acid receptors (RARs), that act as ligand-activated transcription factors. While
      RARs have been extensively studied in jawed vertebrates (that is, gnathostomes)
      and invertebrate chordates, very little is known about the repertoire and
      developmental roles of RARs in cyclostomes, which are extant jawless vertebrates.
      Here, we present the first extensive study of cyclostome RARs focusing on three
      different lamprey species: the European freshwater lamprey, Lampetra fluviatilis,
      the sea lamprey, Petromyzon marinus, and the Japanese lamprey, Lethenteron
      japonicum. RESULTS: We identified four rar paralogs (rar1, rar2, rar3, and rar4)
      in each of the three lamprey species, and phylogenetic analyses indicate a
      complex evolutionary history of lamprey rar genes including the origin of rar1
      and rar4 by lineage-specific duplication after the lamprey-hagfish split. We
      further assessed their expression patterns during embryonic development by in
      situ hybridization. The results show that lamprey rar genes are generally
      characterized by dynamic and highly specific expression domains in different
      embryonic tissues. In particular, lamprey rar genes exhibit combinatorial
      expression domains in the anterior central nervous system (CNS) and the
      pharyngeal region. CONCLUSIONS: Our results indicate that the genome of lampreys
      encodes at least four rar genes and suggest that the lamprey rar complement arose
      from vertebrate-specific whole genome duplications followed by a lamprey-specific
      duplication event. Moreover, we describe a combinatorial code of lamprey rar
      expression in both anterior CNS and pharynx resulting from dynamic and highly
      specific expression patterns during embryonic development. This 'RAR code' might
      function in regionalization and patterning of these two tissues by differentially
      modulating the expression of downstream effector genes during development.

PMID- 25984295
TI  - Reproductive toxicity and meiotic dysfunction following exposure to the
      pesticides Maneb, Diazinon and Fenarimol.
AB  - The comprehensive identification and mechanistic analysis of reproductive
      toxicants constitutes one of the major hurdles in the toxicological assessment of
      chemicals originating from the large number of chemicals to be tested and the
      difficulty in examining germ cells at various stages of their development. We
      previously described the development of an assay in the roundworm Caenorhabditis
      elegans that allows the detection of chemicals bearing aneugenic activity and
      that could be used for the detection of germline toxicity. We present here new
      evidence for the reproductive toxicity of three pesticides identified in our
      germline toxicity assay: Maneb, Diazinon and Fenarimol. We show that all three
      pesticides cause an acute germline nuclear loss in exposed nematodes in a dose
      dependent fashion. The loss of germline nuclei coincides with the meiotic stage
      of pachytene during Prophase I and is dependent on the germline apoptotic
      machinery suggesting activation of a meiotic checkpoint. Further investigation
      revealed a profound dysregulation of the meiotic program revealed by (1) an
      alteration of the kinetics of double strand repair, (2) the disruption of the
      process of chromosome morphogenesis at the end of Prophase I and (3) the
      reorganization of the meiotic differentiation gradient inherent to the C. elegans
      germline following exposure to Maneb and Diazinon. These defects correlate with a
      significant increase in embryonic lethality and a corresponding decrease in the
      number of progeny. These results therefore provide strong evidence for the
      reproductive toxicity of Maneb, Diazinon and Fenarimol rooted in the alteration
      of early steps of germ cell differentiation.

PMID- 25977754
TI  - Challenges and opportunities for early-career Teaching-Focussed academics in the
      biosciences.
AB  - Twenty-seven percent of academics in UK Higher Education (HE) are in Teaching
      Focussed positions, making major contributions to undergraduate programmes in an
      era of high student expectations when it comes to teaching quality. However,
      institutional support for Teaching-Focussed academics is often limited, both in
      terms of peer networking and opportunities for career development. As four early
      career stage Teaching-Focussed academics working in a variety of institutions, we
      explore what motivated our choices to make teaching our primary academic
      activity, and the challenges that we have faced in doing so. In addition to
      highlighting the need for universities to fully recognise the achievements of
      teaching staff, we discuss the role that the various biosciences learned
      societies have in supporting Teaching-Focussed academics. We identify that there
      is a need for the learned societies to come together and pool their expertise in
      this area. The fragmented nature of the Teaching-Focussed academic community
      means that clear sources of national support are needed in order to best enable
      the next generation of bioscience educators to reach their full potential. 

PMID- 25977753
TI  - Ant-App-DB: a smart solution for monitoring arthropods activities, experimental
      data management and solar calculations without GPS in behavioral field studies.
AB  - Field studies on arthropod ecology and behaviour require simple and robust
      monitoring tools, preferably with direct access to an integrated database. We
      have developed and here present a database tool allowing smart-phone based
      monitoring of arthropods. This smart phone application provides an easy solution
      to collect, manage and process the data in the field which has been a very
      difficult task for field biologists using traditional methods. To monitor our
      example species, the desert ant Cataglyphis fortis, we considered behavior, nest
      search runs, feeding habits and path segmentations including detailed information
      on solar position and Azimuth calculation, ant orientation and time of day. For
      this we established a user friendly database system integrating the Ant-App-DB
      with a smart phone and tablet application, combining experimental data
      manipulation with data management and providing solar position and timing
      estimations without any GPS or GIS system. Moreover, the new desktop application
      Dataplus allows efficient data extraction and conversion from smart phone
      application to personal computers, for further ecological data analysis and
      sharing. All features, software code and database as well as Dataplus application
      are made available completely free of charge and sufficiently generic to be
      easily adapted to other field monitoring studies on arthropods or other migratory
      organisms. The software applications Ant-App-DB and Dataplus described here are
      developed using the Android SDK, Java, XML, C# and SQLite Database. 

PMID- 25984298
TI  - Stability of octreotide acetate decreases in a sodium bisulfate concentration
      dependent manner: compatibility study with morphine and metoclopramide
      injections.
AB  - PURPOSE: Sodium bisulfate is known to affect the stability of octreotide.
      However, the critical concentration of sodium bisulfate is not known. Therefore,
      we assessed the critical concentration of sodium bisulfate needed to preserve the
      stability of octreotide using actual drugs containing sodium bisulfate. METHODS:
      Although morphine and metoclopramide preparations are considered to be compatible
      with octreotide, some of their products are known to contain sodium bisulfate.
      Thus, octreotide was mixed with preparations of sodium bisulfate solutions at
      serial concentrations and morphine and metoclopramide preparations containing
      sodium bisulfate, and octreotide stability was then evaluated using high
      performance liquid chromatography. RESULTS: Octreotide concentrations decreased
      significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10
      days when octreotide was mixed with sodium bisulfate solutions at various
      concentrations. A significant decrease in octreotide concentrations also occurred
      when it was mixed with morphine and metoclopramide preparations containing sodium
      bisulfate and stored for 10 days; however, slight decreases were observed in the
      mixture with both preparations and were within the clinically acceptable range
      for morphine preparations. CONCLUSIONS: These results indicate that the residual
      rate of octreotide decreases with time in a sodium bisulfate concentration
      dependent manner when octreotide was mixed with morphine or metoclopramide.
      However, this incompatibility may be clinically acceptable when the final sodium
      bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used
      within 7 days.

PMID- 25984299
TI  - The Academic Surgical Collaborative: Launching a new trainee research
      collaborative.

PMID- 25984300
TI  - Serious neonatal airway obstruction with massive congenital sublingual ranula and
      contralateral occurrence.
AB  - BACKGROUND: Congenital ranulas seldom occur, with bilateral presentation and
      prenatal diagnosis reported very rarely. We believe this is the first reported
      case of a neonate with a antenally diagnosed massive congenital ranula, who went
      on to develop a non-contiguous contralateral ranula, both contributing to
      obstruction in a complex paediatric airway. CASE REPORT: A female neonate was
      born to a non-primagravid mother via a planned elective caesarean section due to
      a lower facial defect and oral cyst. Antenatal aspiration of the pseudocyst was
      performed under ultrasound guidance with limited success. In the immediate post
      natal period a poor airway was observed and the cyst was subsequently
      marsupialised. With the development of macroglossia secondary to oedema and
      tongue base collapse the airway was secured through surgical tracheostomy. A
      subsequent ultrasound scan revealed the presence of a second solitary cystic mass
      on the contralateral side. After careful excision of the contralateral
      pseudocyst, tongue function improved, with the resolution of a safe airway which
      permitted successful decannulation. A planned definitive procedure antenatally
      did not result in the anticipated improvement in function. However the subsequent
      development of a second non-contiguous pseudocyst and further surgical management
      resulted in a safe airway, improved masticator function and the ability to
      thrive. CONCLUSIONS: The prenatal diagnosis of congenital ranulas have been
      seldom reported, with no reported cases of contralateral occurrence and airway
      obstruction from an intraoral ranula. This rare case highlights the need for a
      well considered contingency plan when surgery is required for a neonatal airway
      at risk.

PMID- 25984301
TI  - Narrowing of giant gastric perforation by purse-string suture before omental
      plugging.
AB  - INTRODUCTION: Timely diagnosis of the gastroduodenal perforation usually allows
      primary repair or resection. Treatment of a large gastric perforation is more
      difficult than the common duodenal ulcer perforation by plugging and usually
      requires agastric resection. On the other hand, gastric resection fora
      hemodynamically compromised patient in sepsis hasa high rate of anastomotic
      failure and mortality. Here, we described a practical surgical technique that can
      avoid emergency gastric resection in such situations. PRESENTATION OF CASE: A 83
      year-old female admitted with peritonitis, severe sepsis and hemodynamic
      instability. After the diagnosis of hollow organ perforation and supportive
      therapy, laparotomy revealed a delayed and large (7 cm) gastric perforation.
      Instead of gastrectomy, we downsized the large defect by means of a purse-string
      suture around the perforation and made it suitable for the application of omental
      plugging. DISCUSSION: The patients with poor performance status who are not
      suitable for the gastric resection, a free omental plug fixation to the narrowed
      perforation area by a purse-string suture can overcome the problem. CONCLUSION:
      This method can be keep in mind as a damage control surgery technique in the non
      traumatic abdominal emergencies due to large gastric perforations.

PMID- 25984302
TI  - Franco Basaglia and the radical psychiatry movement in Italy, 1961-78.
AB  - This article provides a short introduction to the life and work of Italian
      radical psychiatrist and mental health reformer Franco Basaglia. A leading figure
      in the democratic psychiatry movement, Basaglia is little known and often
      misunderstood in the English-speaking world. This article will seek to address
      this by highlighting Basaglia's significant role in the struggle for both
      deinstitutionalisation and the human rights of those incarcerated in Italy's
      asylums during the 1960s and 1970s.

PMID- 25984304
TI  - Streptococcus pneumoniae sepsis in a pleural effusion smear with concomitant
      Waldenstrom's macroglobulinemia.
AB  - Usually identification of the causative bacteria for an episode of sepsis is
      achieved using microbiological culture of blood or body fluid. In the case of
      pleural effusion and fever, a microscopic examination of the pleural effusion
      smear to identify the bacteria responsible should be performed immediately to
      optimize the selection of antibiotic therapy regimen. 

PMID- 25984303
TI  - Possible FDA-approved drugs to treat Ebola virus infection.
AB  - There is currently no effective treatment for the Ebola virus (EBOV) thus far.
      Most drugs and vaccines developed to date have not yet been approved for human
      trials. Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna
      block the release of viral particles; however, their clinical dosages are much
      lower than the dosages required for effective EBOV suppression. An alpha-1,2
      glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly
      and secretion. Additionally, the estrogen receptor modulators Clomiphene and
      Toremifene prevent membrane fusion of EBOV and 50-90% of treated mice survived
      after Clomiphene/Toremifene treatments. However, the uptake efficiency of
      Clomiphene by oral administration is very low. Thus, I propose a hypothetical
      treatment protocol to treat Ebola virus infection with a cumulative use of both
      Miglustat and Toremifene to inhibit the virus effectively and synergistically.
      EBOV infection induces massive apoptosis of peripheral lymphocytes. Also,
      cytolysis of endothelial cells triggers disseminated intravascular coagulation
      (DIC) and subsequent multiple organ failures. Therefore, blood transfusions and
      active treatments with FDA-approved drugs to treat DIC are also recommended. 

PMID- 25984305
TI  - Multidisciplinary management of hypohydrotic ectodermal dysplasia - a case
      report.
AB  - Hypohydrotic ectodermal dysplasia is a hereditary disorder, which affects
      ectodermal derivatives. It manifests several abnormalities of the teeth, and is
      commonly inherited through female carriers. This case report presents a patient
      with compromised esthetics and function. A multidisciplinary approach was planned
      involving an oral pathologist, endodontist, orthodontist and a prosthodontist. 

PMID- 25984306
TI  - Induction with azacytidine followed by allogeneic hematopoietic stem cell
      transplantation in a Jehovah's Witness with acute monocytic leukemia.
AB  - We have used a hypomethylating agent instead of conventional chemotherapy to
      induce remission in a young Jehovah's Witness with acute monocytic leukemia to
      avoid severe myelosuppression and blood product support. The treatment was
      consolidated with reduced intensity allogeneic stem cell transplantation. This
      could be an alternative when transfusions must be avoided. 

PMID- 25984307
TI  - Life-threatening necrotizing myometritis, due to Group A streptococcus - still a
      life-threatening condition.
AB  - Puerperal infection with Group A streptococcus (GAS) can present with few
      symptoms and rapidly progress to a life-threatening condition. Often, the
      infection can be treated with antibiotics. Delay in diagnosis increases risk of
      sepsis, multiorgan failure, and death. GAS infection is a differential diagnose
      for all postpartum women with unexplained symptoms. 

PMID- 25984308
TI  - Maxillary Midline diastema closure after replacement of primary teeth with
      implant prosthesis.
AB  - This case shows an excellent esthetic treatment outcome using implant-retained
      crowns replacing maxillary laterals and canines in hypodontia patient with
      unusual incidence of spontaneous diastema closure after the placement of
      implants. To our knowledge, this is the first case report showing maxillary
      midline diastema closure after implant placement. 

PMID- 25984309
TI  - Apoptosis of ileal crypt epithelia after allogeneic bone marrow transplantation
      without graft-versus-host disease.
AB  - Intestinal crypt cell apoptosis may occur after allogeneic bone marrow
      transplantation without clinically overt graft-versus-host disease. We describe
      this phenomenon in a case of a 12-year-old girl who had segments of the ileum
      resected because of a relapse of acute lymphoblastic leukemia. The diagnostic
      difficulties are discussed. 

PMID- 25984310
TI  - Integrating EMDR into an evolutionary-based therapy for depression: a case study.
AB  - We present an intervention in a case of major depression, where eye movement
      desensitization and reprocessing (EMDR) therapy was integrated into an
      evolutionary-based psychotherapy for depression. At the end of the treatment and
      at follow up assessment we observed a more accepting disposition and decreased
      depressive but not anxiety symptoms. 

PMID- 25984311
TI  - Arrhythmogenic right ventricular cardiomyopathy in a patient with schizophrenia.
AB  - People with schizophrenia are at greater risk of cardiovascular morbidity and
      mortality than the general population. Arrhythmogenic right ventricular
      cardiomyopathy is a recognized cause of sudden cardiac death in young people.
      This report discusses the necessity for close cardiac evaluation to reduce
      incidence of sudden death in people with schizophrenia. 

PMID- 25984312
TI  - Endometriosis coexisting with mature cystic teratoma in the same ovary and
      ectopic pregnancy of left fallopian tube: a rare coexistence.
AB  - A coexistence of endometriosis and mature cystic teratoma in the same ovary is a
      rare occurrence although such tumors of ovaries are said to be common in the
      reproductive age group. We report a case of fimbrial ectopic pregnancy combined
      with simultaneous ipsilateral ovarian presentation of endometriosis and mature
      teratoma. 

PMID- 25984313
TI  - Disseminated Cryptococcal infection in an immunocompetent host mimicking plasma
      cell disorder: a case report and literature review.
AB  - Cryptococcosis is a potentially fatal fungal infection caused mainly by
      Cryptocococcus neoformans (CN) species and it rarely infects immunocompetent
      hosts. The outcomes are better only if the condition is suspected and diagnosed
      early and treatment is instituted. 

PMID- 25984314
TI  - Copper deficiency mimicking myelodysplastic syndrome.
AB  - Copper deficiency is a rare cause of pancytopenia that may be mistaken for
      myelodysplastic syndrome. Cytoplasmic vacuolization in erythroid and myeloid
      precursors is found on bone marrow examination. Patients with a history of
      abdominal surgery who present with anemia and neutropenia with dysplastic changes
      should have copper levels checked. 

PMID- 25984315
TI  - Delivery through perineal body and severed external anal sphincter with an intact
      vaginal orifice during a precipitous labor: a case report.
AB  - We present the case of a patient who delivered her baby through the perineal body
      with an intact vaginal introitus. Damage to the perineal body through its
      connection to the external anal sphincter can involve the rectovaginal septum
      with increased morbidity and thought to be linked to rectocele development. 

PMID- 25984316
TI  - Primary hydatid cyst of peritoneum presented as abdominal lump: a rare
      presentation.
AB  - The incidence of primary hydatid cyst of peritoneum is 2%. It can present as a
      palpable abdominal lump. The differential diagnosis is cystic ovarian tumor
      clinically and radiologically. Peritoneal hydatid disease should be included in
      differential diagnosis of sonographically diagnosed pelvic cystic lesion. 

PMID- 25984317
TI  - Natural ear rings.
AB  - Ear lobe keloids are common following ear piercing and these lesions are
      conspicuous and cosmetically unappealing. Multiple methods including surgery,
      radiotherapy, anti mitotic agents, silicone sheet, pressure clips, and
      cryotherapy have been used. The Challenge is to have a good cosmetic outcome with
      minimal recurrence. 

PMID- 25984318
TI  - Roving eye movements in a patient with hypoglycemic coma.
AB  - Roving eye movements are the sign of cortical dysfunction not involving the
      brainstem. This finding is useful in the differential diagnosis of impaired
      consciousness and indicates cerebral damage in patients with hypoglycemic coma. 

PMID- 25984320
TI  - Regenerative Medicine Research: an open access translational medicine journal.

PMID- 25984321
TI  - Chronic alcohol ingestion delays skeletal muscle regeneration following injury.
AB  - BACKGROUND: Chronic alcohol ingestion may cause severe biochemical and
      pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol
      induced events may also prime skeletal muscle for worsened, delayed, or possibly
      incomplete repair following acute injury. As alcoholics may be at increased risk
      for skeletal muscle injury, our goals were to identify the effects of chronic
      alcohol ingestion on components of skeletal muscle regeneration. To accomplish
      this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or
      water that contained 20% alcohol (v/v) for 18-20 wk. Subgroups of mice were
      injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior
      (TA) muscle to initiate degeneration and regeneration processes. Body weights and
      voluntary wheel running distances were recorded during the course of recovery.
      Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers
      of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth
      and fibrotic factors, and fibrosis. RESULTS: Body weights of injured, alcohol-fed
      mice were reduced during the first week of recovery. These mice also ran
      significantly shorter distances over the two weeks following injury compared to
      uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased
      TNFalpha and IL6 gene levels compared to controls 2 days after injury. Total
      protein oxidant stress and alterations to glutathione homeostasis were also
      evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF)
      induction was delayed in injured muscles from alcohol-fed mice which may explain,
      in part, why fiber cross-sectional area failed to normalize 14 days following
      injury. Gene levels of TGFbeta1 were induced early following injury before
      normalizing in muscle from alcohol-fed mice compared to controls. However,
      TGFbeta1 protein content was consistently elevated in injured muscle regardless
      of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and
      14 days of recovery compared to injured controls. CONCLUSIONS: Chronic alcohol
      ingestion appears to delay the normal regenerative response following significant
      skeletal muscle injury. This is evidenced by reduced cross-sectional areas of
      regenerated fibers, increased fibrosis, and altered temporal expression of well
      described growth and fibrotic factors.

PMID- 25984322
TI  - Insulin-like growth factor 1 myocardial expression decreases in chronic alcohol
      consumption.
AB  - BACKGROUND: Alcoholic cardiomyopathy (CMP) is one of the major complications of
      chronic excessive alcohol consumption. The pathogenic mechanisms implicated are
      diverse, inducing functional and structural changes in the myocardium. Insulin
      like Growth Factor 1 (IGF-1) plays an important role in modulating the cell
      cycle, and helps the differentiation and proliferation of cardiac tissue
      inhibiting apoptosis. Experimental studies have suggested the role of IGF-1 in
      alcohol-induced cardiac damage. The aim of the present study was to determine the
      effect of chronic alcohol consumption on IGF-1 myocardial expression and to
      compare this expression in cases of hypertension and other cardiac diseases.
      METHODS: We studied heart samples from human organ donors: 10 healthy donors, 16
      with hypertension, 23 with chronic alcohol consumption and 7 with other causes of
      cardiac disease. IGF-1 myocardial expression was evaluated with a specific
      immunohistochemistry assay using a semi-quantitative method. RESULTS: A
      significant decrease in IGF-1 myocardial expression was observed comparing all
      the cases included with control donors. This decrease in IGF-1 myocardial
      expression was significantly lower in the group of donors with chronic alcohol
      consumption compared to controls. On group evaluation according to the presence
      of CMP, donors with chronic alcohol consumption without CMP presented
      significantly lower IGF-1 expression than controls, whereas donors with chronic
      alcohol consumption with CMP showed a downward trend without achieving
      significance. CONCLUSIONS: Chronic alcohol consumption significantly reduces IGF
      1 myocardial expression. This decrease induced by alcohol is partially
      compensated in the presence of structural myocardial damage.

PMID- 25984323
TI  - Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle
      regeneration compared.
AB  - In tissues characterized by a high turnover or following acute injury,
      regeneration replaces damaged cells and is involved in adaptation to external
      cues, leading to homeostasis of many tissues during adult life. An understanding
      of the mechanics underlying tissue regeneration is highly relevant to
      regenerative medicine-based interventions. In order to investigate the existence
      a leitmotif of tissue regeneration, we compared the cellular aspects of
      regeneration of skin, nerve and skeletal muscle, three organs characterized by
      different types of anatomical and functional organization. Epidermis is a
      stratified squamous epithelium that migrates from the edge of the wound on the
      underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells
      whose neurites are organized in bundles, within an endoneurium of connective
      tissue; they either die upon injury or undergo remodeling and axon regrowth.
      Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle
      fibers, that can temporarily survive in broken pieces; satellite cells residing
      along the fibers form new fibers, which ultimately fuse with the old ones as well
      as with each other to restore the previous organization. Satellite cell
      asymmetrical division grants a reservoir of undifferentiated cells, while other
      stem cell populations of muscle and non-muscle origin participate in muscle
      renewal. Following damage, all the tissues analyzed here go through three phases:
      inflammation, regeneration and maturation. Another common feature is the
      occurrence of cellular de-differentiation and/or differentiation events,
      including gene transcription, which are typical of embryonic development.
      Nonetheless, various strategies are used by different tissues to replace their
      lost parts. The epidermis regenerates ex novo, whereas neurons restore their
      missing parts; muscle fibers use a mixed strategy, based on the regrowth of
      missing parts through reconstruction by means of newborn fibers. The choice of
      either strategy is influenced by the anatomical, physical and chemical features
      of the cells as well as by the extracellular matrix typical of a given tissue,
      which points to the existence of differential, evolutionary-based mechanisms for
      specific tissue regeneration. The shared, ordered sequence of steps that
      characterize the regeneration processes examined suggests it may be possible to
      model this extremely important phenomenon to reproduce multicellular organisms. 

PMID- 25984324
TI  - Cathepsins: a new culprit behind abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a fatal disease defined as an abdominal aortic
      diameter of 3.0 cm or more, where the abdominal aorta exceeds the normal diameter
      by more than 50%. Histopathological changes of AAA mainly include extracellular
      matrix (ECM) remodeling at the abdominal aorta wall, but there is lack of
      specific drugs to treat AAA. Recent studies have reported that lysosomal
      cathepsins could induce vascular remodeling and AAA formation by regulating
      vascular inflammation, medial smooth muscle cell apoptosis, neovascularization,
      and protease expression. Thus, cathepsins are expected to become a new
      therapeutic target for AAA treatment. 

PMID- 25984325
TI  - Current status of induced pluripotent stem cells in cardiac tissue regeneration
      and engineering.
AB  - Myocardial infarction (MI) is associated with damage to the myocardium which
      results in a great loss of functional cardiomyocytes. As one of the most
      terminally differentiated organs, the endogenous regenerative potentials of adult
      hearts are extremely limited and insufficient to compensate for the myocardial
      loss occurring after MI. Consequentially, exogenous regenerative strategies,
      especially cell replacement therapy, have emerged and attracted increasing more
      attention in the field of cardiac tissue regeneration. A renewable source of
      seeding cells is therefore one of the most important subject in the field.
      Induced pluripotent stem cells (iPSCs), embryonic stem cell (ESC)-like cells that
      are derived from somatic cells by reprogramming, represent a promising candidate
      due to their high potentials for self-renewal, proliferation, differentiation and
      more importantly, they provide an invaluable method of deriving patient-specific
      pluripotent stem cells. Therefore, iPSC-based cardiac tissue regeneration and
      engineering has been extensively investigated in recent years. This review will
      discuss the achievements and current status in this field, including development
      of iPSC derivation, in vitro strategies for cardiac generation from iPSCs,
      cardiac application of iPSCs, challenges confronted at present as well as
      perspective in the future. 

PMID- 25984326
TI  - Rejuvenation: an integrated approach to regenerative medicine.
AB  - The word "rejuvenate" found in the Merriam-Webster dictionary is (1) to make
      young or youthful again: give new vigor to, and (2) to restore to an original or
      new state. Regenerative medicine is the process of creating living, functional
      tissues to repair or replace tissue or organ function lost due to age, disease,
      damage, or congenital defects. To accomplish this, approaches including
      transplantation, tissue engineering, cell therapy, and gene therapy are brought
      into action. These all use exogenously prepared materials to forcefully mend the
      failed organ. The adaptation of the materials in the host and their integration
      into the organ are all uncertain. It is a common sense that tissue injury in the
      younger is easily repaired and the acute injury is healed better and faster. Why
      does the elder have a diminished capacity of self-repairing, or why does chronic
      injury cause the loss of the self-repairing capacity? There must be some critical
      elements that are involved in the repair process, but are suppressed in the elder
      or under the chronic injury condition. Rejuvenation of the self-repair mechanism
      would be an ideal solution for functional recovery of the failed organ. To
      achieve this, it would involve renewal of the injury signaling, reestablishment
      of the communication and transportation system, recruitment of the materials for
      repairing, regeneration of the failed organ, and rehabilitation of the renewed
      organ. It thus would require a comprehensive understanding of developmental
      biology and a development of new approaches to activate the critical players to
      rejuvenate the self-repair mechanism in the elder or under chronic injury
      condition. Efforts focusing on rejuvenation would expect an alternative, if not a
      better, accomplishment in the regenerative medicine. 

PMID- 25984327
TI  - Expression of tropomyosin in relation to myofibrillogenesis in axolotl hearts.
AB  - The anatomy, function and embryonic development of the heart have been of
      interest to clinicians and researchers alike for centuries. A beating heart is
      one of the key criteria in defining life or death in humans. An understanding of
      the multitude of genetic and functional elements that interplay to form such a
      complex organ is slowly evolving with new genetic, molecular and experimental
      techniques. Despite the need for ever more complex molecular techniques some of
      our biggest leaps in knowledge come from nature itself through observations of
      mutations that create natural defects in function. Such a natural mutation is
      found in the Mexican axolotl, Ambystoma mexicanum. It is a facultative neotenous
      salamander well studied for its ability to regenerate severed limbs and tail.
      Interestingly it also well suited to studying segmental heart development and
      differential sarcomere protein expression due to a naturally occurring mendelian
      recessive mutation in cardiac mutant gene "c". The resultant mutants are
      identified by their failure to beat and can be studied for extended periods
      before they finally die due to lack of circulation. Studies have shown a
      differential expression of tropomyosin between the conus and the ventricle
      indicating two different cardiac segments. Tropomyosin protein, but not its
      transcript have been found to be deficient in mutant ventricles and sarcomere
      formation can be rescued by the addition of TM protein or cDNA. Although once
      thought to be due to endoderm induction our findings indicate a translational
      regulatory mechanism that may ultimately control the level of tropomyosin protein
      in axolotl hearts. 

PMID- 25984328
TI  - Endothelial progenitor cells in cardiovascular diseases: from biomarker to
      therapeutic agent.
AB  - Regenerative medicine techniques to recover cardiac and vascular function are
      being increasingly investigated as management strategies for cardiovascular
      diseases. Circulating endothelial progenitor cells (EPCs) derived from bone
      marrow are immature cells capable of differentiating into mature endothelial
      cells and play a role in vascular reparative processes and neoangiogenesis. The
      potency of EPCs for cardiovascular regeneration has been demonstrated in many
      preclinical studies and therapeutic utility of EPCs has been evaluated in early
      phase clinical trials. However, the regenerative activity and efficiency of the
      differentiation of EPCs are still limited, and a directed differentiation method
      for EPCs cells has not been fully demonstrated. In this review, we introduce the
      role of circulating EPCs as biomarkers of cardiovascular diseases and medical
      applications of EPCs for cardiovascular regeneration. 

PMID- 25984329
TI  - Cardiac regeneration and diabetes.
AB  - The prevalence of diabetes continues to increase world-wide and is a leading
      cause of morbidity, mortality, and rapidly rising health care costs. Although
      strict glucose control combined with good pharmacological and non-pharmacologic
      interventions can increase diabetic patient life span, the frequency and
      mortality of myocardial ischemia and infarction remain drastically increased in
      diabetic patients. Therefore, more effective therapeutic approaches are urgently
      needed. Over the past 15 years, cellular repair of the injured adult heart has
      become the focus of a rapidly expanding broad spectrum of pre-clinical and
      clinical research. Recent clinical trials have achieved favorable initial
      endpoints with improvements in cardiac function and clinical symptoms following
      cellular therapy. Due to the increased risk of cardiac disease, cardiac
      regeneration may be one strategy to treat patients with diabetic cardiomyopathy
      and/or myocardial infarction. However, pre-clinical studies suggest that the
      diabetic myocardium may not be a favorable environment for the transplantation
      and survival of stem cells due to altered kinetics in cellular homing, survival,
      and in situ remodeling. Therefore, unique conditions in the diabetic myocardium
      will require novel solutions in order to increase the efficiency of cellular
      repair following ischemia and/or infarction. This review briefly summarizes some
      of the recent advances in cardiac regeneration in non-diabetic conditions and
      then provides an overview of some of the issues related to diabetes that must be
      addressed in the coming years. 

PMID- 25984330
TI  - Hypothalamic paraventricular nucleus activation contributes to neurohumoral
      excitation in rats with heart failure.
AB  - Heart failure (HF) is a serious cardiovascular disease and is characterized by
      exaggerated sympathetic activity. In this paper, we review these limited studies,
      with particular emphasis on examining the role of the paraventricular nucleus
      (PVN) in the neurohumoral excitation in HF. The PVN is an important
      neuroendocrine and preautonomic output nucleus, and is considered as the
      important central site for integration of sympathetic nerve activity.
      Accumulating evidences demonstrate that a number of neurohumoral processes are
      involved in the pathophysiology of HF, such as renin-angiotensin system (RAS),
      proinflammatory cytokines (PICs), neurotransmitters, and reactive oxygen species
      (ROS). Recent studies about neurohumoral regulation indicate that angiotensin II
      type1 receptor (AT1-R) is the important product mediated by cytoplasmic nuclear
      factor-kappa B (NF-kappaB) which is up-regulated along with elevated PICs and
      angiotensin II (ANG II) in the PVN of HF rats. These findings suggest that the NF
      kappaB mediates the cross-talk between RAS and PICs in the PVN in HF. The further
      studies indicate that the interaction between AT1-R and NF-kappaB in the PVN
      contributes to oxidative stress and sympathoexcitation by modulating
      neurotransmitters in heart failure, and the superoxide activates NF-kappaB in the
      PVN and contributes to neurohumoral excitation. In conclusion, the neurohumoral
      excitation in HF is based on the interaction of RAS, PICs, ROS, NF-kappaB and
      neurotransmitters in the PVN; and the activated NF-kappaB in the PVN modulates
      the neurotransmitters and contributes to sympathoexcitation in rats with heart
      failure. 

PMID- 25984332
TI  - Human induced pluripotent stem cell for modeling cardiovascular diseases.
AB  - The invention of the induced pluripotent stem cell (iPSC) technology allows
      patient-specific, mature somatic cells to be converted into an unlimited supply
      of pluripotent stem cells (PSCs). These iPSCs can then in turn be differentiated
      into any cell type including neurons, cardiac cells, pancreatic cells, liver
      cells, blood cells or enterocytes. Although cardiovascular disease (CVD) is a
      leading cause of death in the world, the limited cell derivation and cell number
      in cardiac tissue makes it difficult to study the CVDs using the existing cardiac
      cell model. By differentiating the patient-specific iPSCs into cardiomyocytes,
      scientists can generate iPSC-based 'disease in a dish' models and use them to
      better understand disease mechanism. Here we review the current progress in using
      iPSC-derived cardiomyocytes to model human CVDs. 

PMID- 25984331
TI  - Ischemic stroke and repair: current trends in research and tissue engineering
      treatments.
AB  - Stroke, the third leading cause of mortality, is usually associated with severe
      disabilities, high recurrence rate and other poor outcomes. Currently, there are
      no long-term effective treatments for stroke. Cell and cytokine therapies have
      been explored previously. However, the therapeutic outcomes are often limited by
      poor survival of transplanted cells, uncontrolled cell differentiation,
      ineffective engraftment with host tissues and non-sustained delivery of growth
      factors. A tissue-engineering approach provides an alternative for treating
      ischemic stroke. The key design considerations for the tissue engineering
      approach include: choice of scaffold materials, choice of cells and cytokines and
      delivery methods. Here, we review current cell and biomaterial based therapies
      available for ischemic stroke, with a special focus on tissue-engineering
      strategies for regeneration of stroke-affected neuronal tissue. 

PMID- 25984333
TI  - Isolation and characterization of endothelial progenitor cells from Rhesus
      monkeys.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are increasingly becoming a major
      focus of regenerative medicine research and practice. The present study was
      undertaken to establish an appropriate procedure for isolation and
      characterization of EPCs from Rhesus monkeys for regenerative medicine research.
      RESULT: Selective CD34+ and nonselective mononuclear EPCs were isolated from bone
      marrow and cultured under varying conditions. The results showed that
      nonselective mononuclear EPCs were a better choice for high yield of the target
      cells. The cells grew in M 200 better than in EGM-2, and supplementation with
      fetal bovine serum promoted cell proliferation; but serum level at 7.5% was
      better than at 10%. In addition, surface coating of the culture dishes with human
      fibronectin significantly improved the proliferation and ontogeny of the isolated
      EPCs. Immunocytochemistry including detection of markers CD34, CD133 and CD31 and
      double-staining for Ac-LDL and lectin verified the purity of the cultured
      mononuclear EPCs. CONCLUSION: By a thorough analysis, we established a practical
      procedure for isolation and propagation of EPCs from Rhesus monkeys. This
      procedure would help using these valuable cells for regenerative medicine
      research.

PMID- 25984334
TI  - Heart regeneration, stem cells, and cytokines.
AB  - The human heart has limited regenerative capacity, which makes the reparative
      response after the cardiac infarction quite challenging. During the last decade,
      stem cells have become promising candidates for heart repair, owing to their
      potent differentiation capacity and paracrine cytokine secretion. Among the
      different types of stem cells, mesenchymal stem cells have high proliferative
      potential and secrete numerous cytokines, growth factors, and microRNAs. The
      paracrine cytokines play important roles in cardiac regeneration,
      neovascularization, anti-apoptosis, and anti-remodeling mechanisms, among others.
      This review summarizes the cytokines secreted by stem cells and their relative
      signaling pathways, which represent key mechanisms for heart regeneration and may
      serve as a promising future therapeutic strategy for myocardial infarction
      patients. 

PMID- 25984335
TI  - Cell-based therapy in lung regenerative medicine.
AB  - Chronic lung diseases are becoming a leading cause of death worldwide. There are
      few effective treatments for those patients and less choices to prevent the
      exacerbation or even reverse the progress of the diseases. Over the past decade,
      cell-based therapies using stem cells to regenerate lung tissue have experienced
      a rapid growth in a variety of animal models for distinct lung diseases. This
      novel approach offers great promise for the treatment of several devastating and
      incurable lung diseases, including emphysema, idiopathic pulmonary fibrosis,
      pulmonary hypertension, and the acute respiratory distress syndrome. In this
      review, we provide a concise summary of the current knowledge on the attributes
      of endogenous lung epithelial stem/progenitor cells (EpiSPCs), mesenchymal stem
      cells (MSCs) and endothelial progenitor cells (EPCs) in both animal models and
      translational studies. We also describe the promise and challenges of tissue
      bioengineering in lung regenerative medicine. The therapeutic potential of MSCs
      is further discussed in IPF and chronic obstructive pulmonary diseases (COPD). 

PMID- 25984336
TI  - Promising targets of cell death signaling of NR2B receptor subunit in stroke
      pathogenesis.
AB  - Stroke is an acute cerebrovascular disease caused by acute brain artery bursting
      or cerebral embolism that leads to neuronal death and severe dysfunction of
      synaptic transmission. Neuronal damage after stroke remains a major cause of
      morbidity and mortality worldwide and affects 795 000 of lives every year in
      United States. However, effective treatments remain lacking, which makes the
      identification of new therapeutic targets a matter of great importance. N-methyl
      D-aspartate glutamate (NMDA) receptor is important both in the normal synaptic
      transmission and in the neuronal death after stroke. Accumulated evidences show
      NMDA receptor downstream effectors, such as PSD-95, DAPK1, and ERK, had been
      revealed to be linked with neuronal damage. Based on our recent studies, we
      review the promising targets of the NMDA receptor downstream signaling involved
      in stroke treatment. This review will provide the concept of NR2B downstream
      signaling in neuronal death after stroke and provide evidences for developing
      better NMDAR-based therapeutics by targeting downstream proteins. 

PMID- 25984337
TI  - Pilot study: bone marrow stem cells as a treatment for dogs with chronic spinal
      cord injury.
AB  - BACKGROUND: Chronic Spinal Cord injury is a common, severe, and medically
      untreatable disease. Since the functional outcomes of acute and experimental
      chronic spinal cord injury have been shown to improve with stem cell therapy, a
      case study was conducted to test if the application of stem cell also regenerates
      chronic SCI dysfunction. Transplantation of foetal bone marrow stem cells was
      applied in seven dogs with chronic spinal cord injury. Magnetic resonance images
      and assessments of symptoms according to the Olby scale were used to diagnose the
      severity of injury. RESULT: All dogs improved locomotor and sensory function when
      examined 90 days after surgery, and showed increased movement of the hind limbs,
      and were able to stand upright, as well as to take small steps. Tail tone was
      observed in seven dogs, pain reflexes and defecation return were observed in five
      dogs. CONCLUSION: The transplantation of bone marrow stem may be a promising,
      reliable and safe treatment for chronic spinal cord injury.

PMID- 25984338
TI  - Efficacy and cost-effectiveness of screening colonoscopy according to the adenoma
      detection rate.
AB  - BACKGROUND: The adenoma detection rate of the endoscopist has been related to the
      post-colonoscopy interval risk of colorectal cancer. OBJECTIVE: The objective of
      this article is to estimate the impact of adenoma detection rate on the long-term
      colorectal cancer prevention rate. METHODS: A Markov model was constructed to
      simulate the efficacy and cost of colonoscopy screening according to the adenoma
      detection rate of the endoscopist in 100,000 individuals. Post-colonoscopy
      interval colorectal cancer risk and the relative risk of interval cancer among
      endoscopists with different adenoma detection rates were extracted from the
      literature. A 1.5 relative risk was assumed between endoscopists with low and
      average adenoma detection rates, and a relative risk of 11 between those with
      average and high adenoma detection rates. Both efficacy and costs were projected
      over a steady-state American population. RESULTS: Screening colonoscopy performed
      by endoscopists with low adenoma detection rates resulted in a 7% absolute
      reduction in the long-term colorectal cancer incidence prevention rate as
      compared to the same procedure performed by those with an average adenoma
      detection rate (70% vs. 77%). This difference increased to 21% when comparing
      endoscopists with an average with those with a high adenoma detection rate. When
      projected on the US population, this reduced efficacy resulted in an additional
      1728 and 16,123 colorectal cancer cases and the loss of $117 million and $906
      million per year in the two scenarios, respectively. These estimates were
      sensitive to the risk of post-colonoscopy interval colorectal cancer.
      CONCLUSIONS: A substantial reduction in long-term colorectal cancer prevention
      rate may be expected when screening colonoscopy is performed by endoscopists with
      a suboptimal adenoma detection rate. A substantial saving may be expected when
      implementing policies to improve endoscopist adenoma detection rate.

PMID- 25984339
TI  - Increasing ultraviolet light exposure is associated with reduced mortality from
      Clostridium difficile infection.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is an increasingly common cause
      of inpatient mortality. Vitamin D deficiency is associated with more aggressive
      CDI. We aimed to determine if average annual ultraviolet light (UV) exposure was
      associated with mortality in patients with CDI. METHODS: We used the US National
      Inpatient Sample (NIS) from 2004-2011 to assess the mortality risk in patients
      with a diagnosis of CDI (as per ICD-9CM 008.45). Annual average state UV exposure
      was assigned to each hospitalization. Logistic regression was used to determine
      the effects of UV exposure on mortality, controlling for age, gender, race and
      other comorbidities. RESULTS: During the study period, there were 2.61 million
      hospitalizations with a diagnosis of CDI. The mortality rate was 9.0%. In
      univariate analysis, the odds ratio (OR) of inpatient mortality for the UV index
      was 0.97 (95% CI 0.95-0.99; p = 0.008) per unit of UV exposure. In a
      multivariable model adjusting for age, gender, race, Charlson-Deyo index, season
      and coexisting inflammatory bowel disease, the UV index remained a protective
      predictor, with an OR of 0.94 (95% CI 0.92-0.96; p < 0.001). In the multivariate
      model, a seasonal effect was also present, with the highest risk of inpatient
      mortality in the period from January to March (OR 1.11; 95% CI 1.08-1.14) and the
      lowest risk, from July to September (OR 0.95; 95% CI 0.92-0.98). CONCLUSIONS: An
      increase in UV exposure index is associated with a reduced risk of inpatient
      mortality in patients with CDI. A seasonal effect is also present, with the
      highest risk of death during winter months. Further studies exploring the role of
      UV light in CDI are necessary.

PMID- 25984341
TI  - Quaternized chitosans bind onto preexisting biofilms and eradicate pre-attached
      microorganisms.
AB  - Quaternized chitosans, N,N,N-trimethylchitosans (TMC) with different degree of
      quaternization were synthesized by reacting methyl iodide with chitosan. The
      reaction was confirmed by FT-IR and 1H-NMR characterization. Antimicrobial assay
      showed that the prepared TMC had potent biocidal effects against planktonic Gram
      positive bacteria Staphylococcus epidermidis, Gram-negative bacteria Escherichia
      coli, and yeast Candida albicans. Bacterial and fungal biofilms were formed on
      poly(methyl methacrylate) (PMMA) films and then treated with TMC aqueous
      solutions. Zeta potential measurement suggested that TMC bonded onto the
      preexisting biofilms. Biofilm-binding kinetics was evaluated in UV studies using
      phenyl group-labeled TMC as model compounds, which revealed that quaternized
      chitosans bonded onto the preexisting biofilms rapidly. Colony-forming unit (CFU)
      determination and SEM, confocal laser scanning microscopy (CLSM) and fluorescence
      microscopy studies demonstrated that the bonded TMC had powerful biocidal
      activities to eradicate the pre-attached bacterial and fungal cells in the
      preexisting biofilms. The biocompatibility of the TMC samples with rat skin
      fibroblast cells was evaluated in the MTT assay.

PMID- 25984340
TI  - Pure Graphene Oxide Doped Conducting Polymer Nanocomposite for Bio-interfacing.
AB  - Advanced materials that are highly biocompatible and easily modifiable with
      biomolecules are of great importance for bio-interfacing and the development of
      biodevices. Here, a biocompatible conducting polymer based nanocomposite was
      electrochemically synthesized through the electropolymerization of poly(3, 4
      ethylene dioxythiophene) (PEDOT) in the presence of graphene oxide (GO) as the
      only dopant. GO contains many negatively charged carboxyl functional groups and
      is highly dispersible in aqueous solutions, enabling its facile incorporation and
      even distribution throughout the conducting polymer. PEDOT/GO films exhibited
      minimal cytotoxicity after 24 h and supported neuron growth with significantly
      longer neurites than a control PEDOT/PSS film, indicating that the PEDOT/GO film
      provides a positive growth signal to developing neurons. While some of the
      negatively charged functional carboxyl groups of GO "dope" the PEDOT, others are
      exposed freely on the surface of the nanocomposite allowing easy
      functionalization of the PEDOT/GO composite with biomolecules. Functional laminin
      peptide, RNIAEIIKDI (p20), was covalently bound to the surface of the PEDOT/GO
      film and maintained its bioactivity, as evidenced by an increased neurite
      outgrowth from neurons cultured on the functionalized composite surface. The ease
      of biomolecule functionalization of the PEDOT/GO nanocomposite, along with its
      low electrochemical impedance, minimal toxicity and permissiveness to neuron
      growth, underlines its potential as a material for widespread biosensing, neural
      interfacing and tissue engineering applications.

PMID- 25984342
TI  - Two or three primary dose regime for Haemophilus influenzae type b conjugate
      vaccine: meta-analysis of randomized controlled trials.
AB  - Haemophilus influenzae type b (Hib) is an important cause of meningitis and
      pneumonia in children. Despite the availability of Hib conjugate vaccine, many
      countries are still to implement it in their immunization schedule. Before
      introducing the vaccine in routine immunization programs, it is important to know
      not only the cumulative efficacy but also the efficacy of each vaccine dose. The
      primary objective of this review is to find whether two primary dose schedule of
      Hib vaccine is equally efficacious as the standard three primary dose schedule. A
      highly sensitive online search was run using the terms 'Haemophilus Vaccines' or
      'Haemophilus influenzae type b' and 'conjugate vaccine', and Medline (Ovid),
      PubMed, Embase, CENTRAL and Scopus were explored for prospective randomized
      controlled studies. Data were extracted in a predesigned proforma and analyzed
      using RevMan software. Nine randomized studies were included in the analysis.
      Pooled vaccine efficacy using a fixed effects model against confirmed invasive
      Hib disease following the 3, 2 and 1 primary dose schedule were 82% [95%
      confidence interval (CI) 73-87], 79% (95% CI 54-90) and 65% (95% CI 23-84),
      respectively, and the overall efficacy was 80% (95% CI 72-85). To conclude, we
      found that Hib conjugate vaccine is highly efficacious and that the two dose
      regime is as good as the three dose regime. [The protocol was registered with
      PROSPERO (CRD42013004490)]. 

PMID- 25984343
TI  - Parallel genome-scale loss of function screens in 216 cancer cell lines for the
      identification of context-specific genetic dependencies.
AB  - Using a genome-scale, lentivirally delivered shRNA library, we performed
      massively parallel pooled shRNA screens in 216 cancer cell lines to identify
      genes that are required for cell proliferation and/or viability. Cell line
      dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The
      proliferation effect of each shRNA in each cell line was assessed by transducing
      a population of 11M cells with one shRNA-virus per cell and determining the
      relative enrichment or depletion of each of the 54,000 shRNAs after 16 population
      doublings using Next Generation Sequencing. All the cell lines were screened
      using standardized conditions to best assess differential genetic dependencies
      across cell lines. When combined with genomic characterization of these cell
      lines, this dataset facilitates the linkage of genetic dependencies with specific
      cellular contexts (e.g., gene mutations or cell lineage). To enable such
      comparisons, we developed and provided a bioinformatics tool to identify linear
      and nonlinear correlations between these features. 

PMID- 25984344
TI  - Global database of leishmaniasis occurrence locations, 1960-2012.
AB  - The leishmaniases are neglected tropical diseases of significant public health
      importance. However, information on their global occurrence is disparate and
      sparse. This database represents an attempt to collate reported leishmaniasis
      occurrences from 1960 to 2012. Methodology for the collection of data from the
      literature, abstraction of case locations and data processing procedures are
      described here. In addition, strain archives and online data resources were
      accessed. A total of 12,563 spatially and temporally unique occurrences of both
      cutaneous and visceral leishmaniasis comprise the database, ranging in geographic
      scale from villages to states. These data can be used for a variety of mapping
      and spatial analyses covering multiple resolutions. 

PMID- 25984345
TI  - Simplified data access on human skeletal muscle transcriptome responses to
      differentiated exercise.
AB  - Few studies have investigated exercise-induced global gene expression responses
      in human skeletal muscle and these have typically focused at one specific mode of
      exercise and not implemented non-exercise control models. However, interpretation
      on effects of differentiated exercise necessitate direct comparison between
      essentially different modes of exercise and the ability to identify true exercise
      effect, necessitate implementation of independent non-exercise control subjects.
      Furthermore, muscle transcriptome data made available through previous exercise
      studies can be difficult to extract and interpret by individuals that are
      inexperienced with bioinformatics procedures. In a comparative study, we
      therefore; (1) investigated the human skeletal muscle transcriptome responses to
      differentiated exercise and non-exercise control intervention, and; (2) set out
      to develop a straightforward search tool to allow for easy access and
      interpretation of our data. We provide a simple-to-use spread sheet containing
      transcriptome data allowing other investigators to easily see how mRNA of their
      gene(s) of interest behave in skeletal muscle following exercise, both endurance,
      resistance and non-exercise, to better aid hypothesis-driven question in this
      field of research. 

PMID- 25984347
TI  - The UK-DALE dataset, domestic appliance-level electricity demand and whole-house
      demand from five UK homes.
AB  - Many countries are rolling out smart electricity meters. These measure a home's
      total power demand. However, research into consumer behaviour suggests that
      consumers are best able to improve their energy efficiency when provided with
      itemised, appliance-by-appliance consumption information. Energy disaggregation
      is a computational technique for estimating appliance-by-appliance energy
      consumption from a whole-house meter signal. To conduct research on
      disaggregation algorithms, researchers require data describing not just the
      aggregate demand per building but also the 'ground truth' demand of individual
      appliances. In this context, we present UK-DALE: an open-access dataset from the
      UK recording Domestic Appliance-Level Electricity at a sample rate of 16 kHz for
      the whole-house and at 1/6 Hz for individual appliances. This is the first open
      access UK dataset at this temporal resolution. We recorded from five houses, one
      of which was recorded for 655 days, the longest duration we are aware of for any
      energy dataset at this sample rate. We also describe the low-cost, open-source,
      wireless system we built for collecting our dataset. 

PMID- 25984346
TI  - A comprehensive database of the geographic spread of past human Ebola outbreaks.
AB  - Ebola is a zoonotic filovirus that has the potential to cause outbreaks of
      variable magnitude in human populations. This database collates our existing
      knowledge of all known human outbreaks of Ebola for the first time by extracting
      details of their suspected zoonotic origin and subsequent human-to-human spread
      from a range of published and non-published sources. In total, 22 unique Ebola
      outbreaks were identified, composed of 117 unique geographic transmission
      clusters. Details of the index case and geographic spread of secondary and
      imported cases were recorded as well as summaries of patient numbers and case
      fatality rates. A brief text summary describing suspected routes and means of
      spread for each outbreak was also included. While we cannot yet include the
      ongoing Guinea and DRC outbreaks until they are over, these data and compiled
      maps can be used to gain an improved understanding of the initial spread of past
      Ebola outbreaks and help evaluate surveillance and control guidelines for
      limiting the spread of future epidemics. 

PMID- 25984348
TI  - Charting the complete elastic properties of inorganic crystalline compounds.
AB  - The elastic constant tensor of an inorganic compound provides a complete
      description of the response of the material to external stresses in the elastic
      limit. It thus provides fundamental insight into the nature of the bonding in the
      material, and it is known to correlate with many mechanical properties. Despite
      the importance of the elastic constant tensor, it has been measured for a very
      small fraction of all known inorganic compounds, a situation that limits the
      ability of materials scientists to develop new materials with targeted mechanical
      responses. To address this deficiency, we present here the largest database of
      calculated elastic properties for inorganic compounds to date. The database
      currently contains full elastic information for 1,181 inorganic compounds, and
      this number is growing steadily. The methods used to develop the database are
      described, as are results of tests that establish the accuracy of the data. In
      addition, we document the database format and describe the different ways it can
      be accessed and analyzed in efforts related to materials discovery and design. 

PMID- 25984349
TI  - The Icelandic 16-electrode electrohysterogram database.
AB  - External recordings of the electrohysterogram (EHG) can provide new knowledge on
      uterine electrical activity associated with contractions. Better understanding of
      the mechanisms underlying labor can contribute to preventing preterm birth which
      is the main cause of mortality and morbidity in newborns. Promising results using
      the EHG for labor prediction and other uses in obstetric care are the drivers of
      this work. This paper presents a database of 122 4-by-4 electrode EHG recordings
      performed on 45 pregnant women using a standardized recording protocol and a
      placement guide system. The recordings were performed in Iceland between 2008 and
      2010. Of the 45 participants, 32 were measured repeatedly during the same
      pregnancy and participated in two to seven recordings. Recordings were performed
      in the third trimester (112 recordings) and during labor (10 recordings). The
      database includes simultaneously recorded tocographs, annotations of events and
      obstetric information on participants. The publication of this database enables
      independent and novel analysis of multi-electrode EHG by the researchers in the
      field and hopefully development towards new life-saving technology. 

PMID- 25984350
TI  - Long-term observation of amphibian populations inhabiting urban and forested
      areas in Yekaterinburg, Russia.
AB  - This article presents data derived from a 36 year-long uninterrupted
      observational study of amphibian populations living in the city and vicinity of
      Yekaterinburg, Russia. This area is inhabited by six amphibian species. Based on
      a degree of anthropogenic transformation, the urban territory is divided into
      five highly mosaic zones characterized by vegetation, temperature, and a
      distinctive water pollution profile. Population data is presented year-by-year
      for the number of animals, sex ratio, and species-specific fecundity including
      the number and quality of spawns for the following amphibian species:
      Salamandrella keyserligii, Rana arvalis, R. temporaria, Lissotriton vulgaris, and
      Pelophylax ridibundus. These data provide an excellent opportunity to assess an
      urban environment from an animal population-wide perspective, as well as
      revealing the forces driving animal adaptation to the anthropogenic
      transformation of habitats. 

PMID- 25984351
TI  - Genome-wide RNAi screen for synthetic lethal interactions with the C. elegans
      kinesin-5 homolog BMK-1.
AB  - Kinesins are a superfamily of microtubule-based molecular motors that perform
      various transport needs and have essential roles in cell division. Among these,
      the kinesin-5 family has been shown to play a major role in the formation and
      maintenance of the bipolar mitotic spindle. Moreover, recent work suggests that
      kinesin-5 motors may have additional roles. In contrast to most model organisms,
      the sole kinesin-5 gene in Caenorhabditis elegans, bmk-1, is not required for
      successful mitosis and animals lacking bmk-1 are viable and fertile. To gain
      insight into factors that may act redundantly with BMK-1 in spindle assembly and
      to identify possible additional cellular pathways involving BMK-1, we performed a
      synthetic lethal screen using the bmk-1 deletion allele ok391. We successfully
      knocked down 82% of the C. elegans genome using RNAi and assayed viability in bmk
      1(ok391) and wild type strains using an automated high-throughput approach based
      on fluorescence microscopy. The dataset includes a final list of 37 synthetic
      lethal interactions whose further study is likely to provide insight into kinesin
      5 function. 

PMID- 25984352
TI  - A user-friendly database of coastal flooding in the United Kingdom from 1915
      2014.
AB  - Coastal flooding caused by extreme sea levels can be devastating, with long
      lasting and diverse consequences. Historically, the UK has suffered major
      flooding events, and at present 2.5 million properties and L150 billion of assets
      are potentially exposed to coastal flooding. However, no formal system is in
      place to catalogue which storms and high sea level events progress to coastal
      flooding. Furthermore, information on the extent of flooding and associated
      damages is not systematically documented nationwide. Here we present a database
      and online tool called 'SurgeWatch', which provides a systematic UK-wide record
      of high sea level and coastal flood events over the last 100 years (1915-2014).
      Using records from the National Tide Gauge Network, with a dataset of exceedance
      probabilities and meteorological fields, SurgeWatch captures information of 96
      storms during this period, the highest sea levels they produced, and the
      occurrence and severity of coastal flooding. The data are presented to be easily
      assessable and understandable to a range of users including, scientists, coastal
      engineers, managers and planners and concerned citizens. 

PMID- 25984353
TI  - Higher BMI is associated with reduced brain volume in heart failure.
AB  - BACKGROUND: Heart failure (HF) patients are at risk for structural brain changes
      due to cerebral hypoperfusion. Past work shows obesity is linked with reduced
      cerebral blood flow and associated with brain atrophy in healthy individuals,
      although its effects on the brain in HF are unclear. This study examined the
      association among body mass index (BMI), cerebral perfusion, and brain volume in
      HF patients. RESULTS: Eighty HF patients underwent transcranial Doppler
      sonography to quantify cerebral blood flow velocity of the middle cerebral artery
      (CBF-V of the MCA) and brain magnetic resonance imaging (MRI) to quantify total
      brain, total and subcortical gray matter, white matter volume, and white matter
      hyperintensities. Body mass index (BMI) operationalized weight status. Nearly 45%
      of HF patients exhibited a BMI consistent with obesity. Regression analyses
      adjusting for medical variables, demographic characteristics, and CBF-V of the
      MCA, showed increased BMI was associated with reduced white matter volume (p
      <.05). BMI also interacted with cerebral perfusion to impact total gray matter
      volume, but this pattern did not emerge for any other MRI indices (p < 0.05).
      CONCLUSIONS: Our findings suggest increased BMI negatively affects brain volume
      in HF, and higher BMI interacts with cerebral perfusion to impact gray matter
      volume. The mechanisms for these findings remain unclear and likely involve
      multiple physiological processes. Prospective studies are needed to elucidate the
      exact pattern and rates of brain changes in obese HF persons.

PMID- 25984355
TI  - Reasons to participate in European Society of Thoracic Surgeons database.
AB  - The process of data collection inevitably involves costs at various levels.
      Nevertheless, this effort is essential to base our knowledge and the consequent
      decision making on solid foundations. The European Society of Thoracic Surgeons
      (ESTS) database collects a large amount of data on general thoracic surgery
      derived from about 60 units representative of 11 nations. Since its beginning in
      2001, the ESTS database has contributed to increase the knowledge and the quality
      of care in our specialty. The present paper illustrates the ultimate finalities
      and the obtained results of this data collection, providing a broad overview of
      the motivations to participate to the ESTS database. 

PMID- 25984356
TI  - Research and education in thoracic surgery: the European trainees' perspective.
AB  - Thoracic surgery training within Europe is diverse and a consensus may help to
      harmonise the training. Currently, training for thoracic surgery compromises
      thoracic, cardiothoracic and aspects of general surgical training. The
      recognition of specialist degrees should be universal and equal. Between
      different nations significant differences in training exist, especially in
      general surgery rotations and in the role of oesophageal surgery. The European
      board examination for thoracic surgery is one of the key ways to achieve
      harmonisation within the European Union (EU) and internationally. Further support
      and encouragement may be beneficial to promote diverse and engaging fellowships
      and clinical exchange programmes between nations. International fellowships may
      even benefit young residents, in both clinical and academic settings. Many
      studies currently would benefit from multi-centre and multi-national design,
      enhancing the results and giving better understanding of clinical scenarios.
      Educational content provided by independent organisations should be more
      recognised as an integral part in both resident training and continuing
      development throughout surgeons' careers. During annual society meetings,
      trainees should have some sessions that are aimed at enhancing their training and
      establishing networks of international peers. 

PMID- 25984354
TI  - Applications of CRISPR-Cas9 mediated genome engineering.
AB  - Targeted mutagenesis based on homologous recombination has been a powerful tool
      for understanding the mechanisms underlying development, normal physiology, and
      disease. A recent breakthrough in genome engineering technology based on the
      class of RNA-guided endonucleases, such as clustered regularly interspaced short
      palindromic repeats (CRISPR)-associated Cas9, is further revolutionizing biology
      and medical studies. The simplicity of the CRISPR-Cas9 system has enabled its
      widespread applications in generating germline animal models, somatic genome
      engineering, and functional genomic screening and in treating genetic and
      infectious diseases. This technology will likely be used in all fields of
      biomedicine, ranging from basic research to human gene therapy. 

PMID- 25984357
TI  - Robotic lobectomy and segmentectomy for lung cancer: results and operating
      technique.
AB  - Video-assisted thoracic surgery (VATS) is a minimally invasive approach with
      several advantages over open thoracotomy for the surgery of lung cancer but also
      some limitations like rigid instruments and suboptimal vision. Robot technology
      is an evolution of manual videothoracoscopy introduced to overcome these
      limitations maintaining the advantages related to low invasiveness. More
      intuitive movements, greater flexibility and high definition three-dimensional
      vision are advantages of the robotic approach. Different studies demonstrate that
      robotic lobectomy and segmentectomy are feasible and safe with long term outcome
      similar to that of open/VATS approaches, however no randomised comparison are
      available and benefits in terms of quality of life (QOL) and pain need to be
      demonstrated yet. Several different robotic techniques are currently employed and
      differ for number of robotic arms (three versus four), the use of CO2
      insufflation, timing of utility incision and the port positioning. The four arms
      robotic approach with anterior utility incision is the technique described by the
      authors. Indications to perform robotic lung resections may be more extensive
      than those of traditional videothoracoscpic approach and includes patients with
      locally advanced disease after chemotherapy or those requiring anatomical
      segmentectomy. Learning curve of vats and robotic lung resection is similar. High
      capital and running costs are the most important disadvantages. Entry of
      competitor companies should drive down costs. 

PMID- 25984358
TI  - Nurse led Patient Education Programme for patients undergoing a lung resection
      for primary lung cancer.
AB  - There has been an increase in the number of patients undergoing lung resection
      for primary or suspected primary lung cancer in the UK due to improved staging
      techniques, dedicated thoracic surgeons and other initiatives such as
      preoperative pulmonary rehabilitation. This has had an impact on local healthcare
      resources requiring new ways of delivering thoracic surgical services. When
      considering service changes, patient reported outcomes are pivotal in terms of
      ensuring that the experience of care is enhanced and may include elements such as
      involving patients in their care, reducing the length of inpatient stay and
      reducing postoperative complications. The implementation of a thoracic surgical
      Patient Education Programme (PEP) has the potential to address these measures and
      improve the psychological and physical wellbeing of patients who require a lung
      resection. It may also assist in their care as an inpatient and to enhance
      recovery after surgery both in the short and long term. 

PMID- 25984360
TI  - Patient safety in thoracic surgery and European Society of Thoracic Surgeons
      checklist.
AB  - Improving patient safety seems to be a new interesting clinical subject but, in
      fact, it is no new. It has to do with one of the oldest ethical principles of our
      profession: curing and not harming. The important research that has been done in
      a short period of time has brought in new insight to this complex area that is
      fast developing. The creation of safety managing systems will allow coordinating
      efforts from very different, although complementary, areas to create real safety
      culture and safety climate in every organization. In the surgical settings,
      teamwork is basic to provide good quality of care. Safety leaders in every team
      have an important role in establishing priorities, summarizing proposals,
      coordinating efforts, launching new initiatives and transmitting that safety
      efforts are worth taken. Preparedness and anticipation are key points for
      avoiding most of the diverse types of patient harm that can occur. As has been
      published, a great number of errors can be avoided simply using crosscheck based
      on specialized checklist that reviews every important detail of the procedure.
      This strategy has been demonstrated very useful at other high risk industries
      such as aviation, nuclear or food management. The Safe Surgery Saves Lives
      program launched in 2002 by the WHO has taught us that improvement is possible
      using a simple checklist. More complex and detail checklist can be more adequate
      for more complex procedures and settings. The proposed ESTS checklist reviews
      different areas of possible error in deeper detail allowing the finest adjustment
      of the patient before the skin incision. It has been recently released to the
      general thoracic community and monitors its use and usefulness has to be
      warrantied. 

PMID- 25984359
TI  - Quality of life after lung resection for lung cancer.
AB  - Radical and palliative treatments for non-small cell lung cancer (NSCLC) have
      been reported to have a significant impact on the patient quality of life (QoL).
      The increasing improvements in lung cancer diagnosis and cures in recent years
      have changed the perspectives of quantity and quality of the life after cancer in
      these patients. However, despite a growing interest about patient reported
      outcome measures (PROMs) in surgical oncology, we are quite distant from a
      routine collection of QoL data after pulmonary resection for NSCLC. The presence
      of this gap is due to several reasons: the lack of validated surgical-specific
      questionnaires, the inappropriate consideration of traditional objective
      parameters as surrogates of QoL outcomes and the difficulties in dealing with
      missing items in this type of research. However, a recent the European Society of
      Thoracic Surgeons (ESTS) survey exploring the use of QoL data in our field has
      revealed that almost half of the units responding to the questionnaire collect
      QoL informations from their patients. Increased consensus and collaboration
      between surgeons are needed to include routinely PROMs in randomized controlled
      trials. The objective of this paper is to review the best available evidence
      published in the literature and regarding QoL after lung resection for cancer,
      aiming at identifying topics deserving further investigations. 

PMID- 25984361
TI  - The association between surgical volume, survival and quality of care.
AB  - Improving surgical outcomes is important to the thoracic surgical community and
      operative mortality is often used as a benchmark to gauge the quality of lung
      resection. In lung cancer surgery, increasing hospital volume is associated with
      better survival although the categorisation of procedure volume is arbitrary.
      When US and UK data are scrutinised, the association holds true for increasingly
      higher volumes up to 150 resection per year and more. The reason may be due to
      better infrastructure, better-staffed units, more resources and wider specialist
      and technology-based services in higher volume centers. For individual surgeon
      volume, reports are not consistent. However, studies suggest that surgeon sub
      specialty is an important consideration. The results of general thoracic surgeons
      and cardiac surgeons are reported to be better than general surgeons for lung
      resection surgery, and the effects of specialty training was also associated with
      an increase in the number of patients undergoing lung resection. We conclude that
      the current evidence strongly supports the association between increasing
      hospital volume with lower mortality and improved long-term survival following
      lung resection. Whilst the data presented supports centralization of lung cancer
      surgery in high volume hospitals, patient choice and the threshold of quality of
      improvement required to overcome travel and closure of local services need to be
      considered. 

PMID- 25984363
TI  - Multidisciplinary management of advanced lung neuroendocrine tumors.
AB  - The optimal clinical management of aggressive/advanced lung neuroendocrine tumors
      (NETs) is still debated, due to their rarity and the lack of prospective
      randomized studies. Results derive from retrospective mono-Institutional series,
      and few dedicated prospective trials, recently designed, are still ongoing. In
      low-grade tumors [bronchial carcinoids (BCs)] surgery, whenever feasible, remains
      the mainstay of treatment, and chemo/radiotherapy (RT) should be reserved to
      progressive diseases (PD). In case of resected N1-N2 BCs, a "watch and see"
      policy associated with a close clinical/radiological follow-up is recommended.
      Somatostatin analogs (SSA) seem to be effective in controlling BCs associated
      endocrine syndromes, while SSA antiproliferative effect has also been reported in
      the past. Targeted therapy with new drugs (Everolimus) seems to be very
      promising, but further trials are needed. Surgery alone is not sufficient to
      treat high-grade NETs: adjuvant CT is required also in early stages. Platinum
      Etoposide regimen demonstrated to be the most effective; irinotecan and other
      biological drugs are considered very promising. In conclusion, the management of
      advanced lung NETs should be individualized by multidisciplinary teams which
      include Medical and Radiation Oncologists, Surgeons, Pathologists,
      Pulmonologists, Endocrinologists, Interventional Radiologists, and the prognosis
      is mainly dependent on tumor grade and its anatomical extent. 

PMID- 25984364
TI  - Nuss technique in pectus excavatum: a mono-institutional experience.
AB  - BACKGROUND: Pectus excavatum (PE) is the most common anomaly of the anterior
      chest wall. Prior PE was corrected by a modified Ravitch operation, but since
      Nuss published his minimal technique in 1998, most surgeons have preferred this
      technique. METHODS: Since 2001 the modified Nuss procedure has routinely been
      used for correction of more than 1,500 patients at Aarhus University Hospital. In
      the time period between January 1, 2011 and January 31, 2015, 675 patients have
      been corrected. The median age was 16 years (range, 11-58 years). All patients
      had preoperatively an epidural catheter and the operations were done in general
      anaesthesia. The postoperative pain treatment was planned for 4-5 weeks and the
      patients were routinely seen in the outpatient clinic 6 weeks after surgery and
      the bars removed after 3 years. RESULTS: Four hundred-and-fifty patients had one
      bar, 216 patients with two bars and nine patients with three bars inserted. The
      median length of the bar was 10 inch. The median duration of the operation was 29
      minutes. The median postoperative stay was 3 days. No death, cardiac perforation
      or deep infection occurred and only 5% of the patients experienced a
      complication. CONCLUSIONS: The Nuss procedure should still be considered in the
      treatment of PE. To my opinion, it should be the choice for correction of PE. The
      short bar should be used to achieve the best stability of the system, to obtain a
      good cosmetic result, a reduced dysfunction motion of the chest wall and an
      increased cardiac performance.

PMID- 25984362
TI  - Lung cancer screening: identifying the high risk cohort.
AB  - Low dose computed tomography (LDCT) is a viable screening tool for early lung
      cancer detection and mortality reduction. In practice, the success of any lung
      cancer screening programme will depend on successful identification of
      individuals at high risk in order to maximise the benefit-harm ratio. Risk
      prediction models incorporating multiple risk factors have been recognised as a
      method of identifying individuals at high risk of developing lung cancer.
      Identification of individuals at high risk will facilitate early diagnosis,
      reduce overall costs and also improve the current poor survival from lung cancer.
      This review summarises the current methods utilised in identifying high risk
      cohorts for lung cancer as proposed by the Liverpool Lung Project (LLP) risk
      model, Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial risk
      models and the prediction model for lung cancer death using quintiles. In
      addition, the cost-effectiveness of CT screening and future perspective for
      selecting high risk individuals is discussed. 

PMID- 25984365
TI  - CD137 enhancement of HPV positive head and neck squamous cell carcinoma tumor
      clearance.
AB  - Standard-of-care cisplatin and radiation therapy (CRT) provides significant tumor
      control of human papillomavirus (HPV)-mediated head and neck squamous cell
      carcinomas (HNSCCs); this effectiveness depends on CRT-mediated activation of the
      patient's own immune system. However, despite good survival, patients suffer
      significant morbidity necessitating on-going studies to define novel therapies
      that alleviate this burden. Given the role of the immune system in tumor
      clearance, immune modulation may further potentiate the CRT-activated response
      while potentially decreasing morbidity. CD137, an inducible cell surface receptor
      found on activated T cells, is involved in differentiation and survival signaling
      in T cells upon binding of its natural partner (CD137L). A number of studies have
      shown the effectiveness of targeting this immune-stimulatory pathway in regards
      to tumor clearance. Here we test its role in HPV+ HNSCC tumor clearance using a
      previously characterized mouse model. We show that amplification of this
      stimulatory pathway synergizes with CRT for enhanced tumor clearance.
      Interestingly, tumor clearance is further potentiated by local tumor cell
      expression of CD137L. 

PMID- 25984367
TI  - COMPARISON OF NATURAL AND SYNTHETIC MATERIALS TO IMPROVE HEARING AFTER
      OBLITERATION OF THE MASTOID CAVITY.
AB  - BACKGROUND: Indications for removal of mastoid air cells and obliterating the
      mastoid cavity vary considerably from surgeon to surgeon. Various obliteration
      techniques have been recommended to eliminate open cavity problems. Here we
      investigated the difference between natural and synthetic filling materials to
      improve hearing after obliteration of the mastoid cavity. SETTING: Academic
      tertiary care medical centers (Al-Azhar and Ain-Shams University Hospitals).
      STUDY DESIGN: Retrospective comparative study included 60 patients divided into 2
      equal groups. METHODS: The study was conducted over 6 years from 2008-14. The
      mean follow-up time was 3.5 years. RESULTS: We found that serviceable hearing
      (<=30 dB) was obtained after surgery in 52 patients (86.6%). In cases where
      natural materials were used in reconstruction, the average gain in AC was 25.5 dB
      and in BC it was 1.1 dB, while in cases where synthetic materials were used the
      average gain in AC was 26 dB and in BC it was 0.5 dB. There was significant
      improvement in the mean postoperative AC compared to the mean preoperative AC.
      However, there was no statistically significant difference between the use of
      natural and synthetic materials in improving postoperative hearing. CONCLUSIONS:
      Both natural and synthetic materials help in improvement of hearing after
      obliteration of the mastoid cavity. There is no statistically significant
      difference between the materials.

PMID- 25984368
TI  - Autologous advanced tenon grafting combined with conjunctival flap in
      scleromalacia after pterygium excision.
AB  - Purpose. To evaluate the efficacy of autologous tenon grafting combined with
      conjunctival flap as a treatment for scleromalacia or scleral thinning after
      pterygium excision without any additional donor graft tissue. Methods. Twenty-six
      cases underwent autologous advanced tenon grafting combined with sliding or
      rotating conjunctival flap for scleromalacia after pterygium surgery ranging from
      2 years to 30 years. The extent of scleral defect measured from 2.0 mm to 6.8 mm
      in diameter. The cosmetic outcome was defined as complete resolution of
      scleromalacia or completely conjunctival reepithelialization and firm adhesion
      between subtenon and scleral tissue over scleral thinning without significant
      complications. Results. All cases achieved the covering of conjunctival and tenon
      or subtenon tissue over scleromalacia or scleral thinning with this procedure.
      Preoperative pain, inflammation, and choroidal exposure disappeared after
      surgery. Immediate postoperative complications, such as large wound dehiscence or
      reopening of the scleral wound, did not occur in any of the patients. There were
      no significant clinical complications during the mean postoperative follow-up
      period of 14.17 months in all cases. Conclusions. We obtained excellent outcome
      with fewer complications after autologous advanced tenon graft and conjunctival
      flap, without an additional donor graft, in scleromalacia or scleral thinning
      caused by previous pterygium excision. 

PMID- 25984369
TI  - Pharmacophore Modelling and 3D-QSAR Studies on N(3)-Phenylpyrazinones as
      Corticotropin-Releasing Factor 1 Receptor Antagonists.
AB  - Pharmacophore modelling-based virtual screening of compound is a ligand-based
      approach and is useful when the 3D structure of target is not available but a few
      known active compounds are known. Pharmacophore mapping studies were undertaken
      for a set of 50 N(3)-phenylpyrazinones possessing Corticotropin-releasing Factor
      1 (CRF 1) antagonistic activity. Six point pharmacophores with two hydrogen bond
      acceptors, one hydrogen bond donor, two hydrophobic regions, and one aromatic
      ring as pharmacophoric features were developed. Amongst them the pharmacophore
      hypothesis AADHHR.47 yielded a statistically significant 3D-QSAR model with 0.803
      as R (2) value and was considered to be the best pharmacophore hypothesis. The
      developed pharmacophore model was externally validated by predicting the activity
      of test set molecules. The squared predictive correlation coefficient of 0.91 was
      observed between experimental and predicted activity values of test set
      molecules. The geometry and features of pharmacophore were expected to be useful
      for the design of selective CRF 1 receptor antagonists. 

PMID- 25984370
TI  - Anaphylactoid Reaction from IV Contrast Dye Causing Ischemic Colitis with Portal
      Venous Gas.
AB  - Portal venous gas is a radiographic finding with numerous causes. The most common
      etiologies include bowel ischemia or other intra-abdominal catastrophes. The
      finding of portal venous gas carries a high mortality rate. We report the first
      case of portal venous gas associated with anaphylactoid reaction to intravenous
      contrast dye in a middle-aged woman. This was likely secondary to anaphylactoid
      induced ischemic colitis. This patient was managed conservatively and had a good
      outcome. 

PMID- 25984371
TI  - Primary lymphoma of bone presenting as spindle cell neoplasm of the vertebral
      body: a case report and review of the literature.
AB  - Spindle cell variant of lymphoma is a very rare but known disease entity that can
      mimic a sarcoma. Diagnosis can be even more challenging if the only site of the
      disease is in the bone. We report a case of primary lymphoma of bone with spindle
      cell morphology which was successfully treated with a combination of surgery,
      chemotherapy, and radiotherapy. 

PMID- 25984372
TI  - Group d salmonella urinary tract infection in an immunocompetent male.
AB  - A 62-year-old male with past medical history of benign prostatic hyperplasia
      presented to the emergency department with complaints of decreased urinary flow,
      inability to fully empty his bladder, and gross hematuria. Physical examination
      was unremarkable. Urinalysis revealed large amount of blood and more than 700
      white blood cells suggesting a urinary tract infection. Urine culture grew group
      D Salmonella greater than 100,000 colony-forming units per mL. He was prescribed
      6 weeks of trimethoprim/sulfamethoxazole and had resolution of symptoms.
      Retrospectively, he reported a 3-day history of watery diarrhea about a week
      prior to onset of urinary symptoms that was presumed to be the hematogenous
      source in this case. Urinary tract infection from nontyphoidal Salmonella (NTS)
      is rare and is usually associated with immunosuppression, chronic diseases, such
      as diabetes or structural abnormalities of the genitourinary tract. Genitourinary
      tract abnormalities previously reported in the literature that predispose to
      nontyphoidal Salmonella urinary tract infection include nephrolithiasis, chronic
      pyelonephritis, retrovesicular fistula, urethrorectal fistula, hydrocele, and
      post-TURP. We present an exceedingly uncommon case of 62-year-old male with group
      D Salmonella urinary tract infection predisposed by his history of benign
      prostatic hyperplasia. 

PMID- 25984373
TI  - Hypoglycemia-induced hemiparesis in a diabetic woman after childbirth.
AB  - A 24-year-old female with type 1 diabetes mellitus presented with hemiparesis
      induced by hypoglycemia. She was hospitalized because she has noticed a weakness
      of her right hand and leg three days after childbirth. On physical examination
      she had an expressive dysphasia and right side hemiparesis with facial drop.
      Hypoglycemia is rarely associated with hemiparesis and it is often overlooked,
      especially when it happens in patients at higher risk of other diseases
      frequently associated with hemiparesis. Although sporadical cases of hypoglycemia
      induced hemiparesis were reported, the clear pathophysiology behind this is not
      well determined. However, any individual case is important in order to increase
      the awareness of hypoglycemia as an important etiology of this condition. 

PMID- 25984374
TI  - A case of ultrasound diagnosis of fetal hiatal hernia in late third trimester of
      pregnancy.
AB  - Congenital hiatal hernia is a condition characterized by herniation of the
      abdominal organs, most commonly the stomach, through a physiological but overlax
      esophageal hiatus into the thoracic cavity. Prenatal diagnosis of this anomaly is
      unusual and only eight cases have been reported in the literature. In this paper
      we describe a case of congenital hiatal hernia that was suspected at ultrasound
      at 39 weeks' gestation, on the basis of a cystic mass in the posterior
      mediastinum, juxtaposed to the vertebral body. Postnatal upper gastrointestinal
      tract series confirmed the prenatal diagnosis. Postnatal management was planned
      with no urgency. Hiatal hernia is not commonly considered in the differential
      diagnosis of fetal cystic chest anomalies. This rare case documents the
      importance of prenatal diagnosis of this anomaly for prenatal counseling and
      postnatal management. 

PMID- 25984375
TI  - A rare initial presentation of gastric cancer with multiple osteolytic lesions.
AB  - Gastric cancer is the 12th leading cause of cancer-related deaths in the United
      States and commonly metastasizes to the bones. However, the presentation of
      gastric cancer as bony metastases without preceding gastrointestinal symptoms is
      rare which has been infrequently reported in the literature. Moreover,
      leptomeningeal carcinomatosis is an unusual complication of gastric cancer
      accounting for less than 1 percent of these patients. We present a unique case of
      a middle aged male who presented to the emergency department with worsening
      backache which started one month priorly. The only abnormal laboratory test was
      an elevated alkaline phosphatase of 154 IU/L. The imaging of his spine showed
      osteolytic lesions which on biopsy revealed signet ring cells. A small 2 cm
      ulcerated mass was found on esophagogastroduodenoscopy at the gastric cardia
      which on biopsy revealed signet ring gastric carcinoma. The patient received
      chemotherapy with capecitabine and oxaliplatin as well as radiation and showed a
      good response initially. A few months later, he presented with persistent
      worsening headaches and on brain imaging was found to have leptomeningeal
      carcinomatosis. Ten months after the diagnosis of gastric carcinoma, he passed
      away. 

PMID- 25984376
TI  - Nystagmus in laurence-moon-biedl syndrome.
AB  - Introduction. Laurence-Moon-Biedl (LMB) syndrome is a rare autosomal-recessive
      ciliopathy with manifold symptomatology. The cardinal clinical features include
      retinitis pigmentosa, obesity, intellectual delay, polydactyly/syndactyly, and
      hypogenitalism. In this paper, the authors report on three siblings with Laurence
      Moon-Biedl syndrome associated with a probable pseudocycloid form of congenital
      nystagmus. Methods. This was a case study conducted at King Khaled Hospital.
      Results. The authors assert that the nystagmus in Laurence-Moon-Biedl syndrome is
      essentially similar to idiopathic motor-defect nystagmus and the nystagmus seen
      in optic nerve hypoplasia, ocular albinism, and bilateral opacities of the ocular
      media. Conclusion. The data support the previous hypothesis that there is a
      common brain stem motor abnormality in sensory-defect and motor-defect nystagmus.

PMID- 25984377
TI  - Clinical findings and genetic expression profiling of three pigmented lesions of
      the optic nerve.
AB  - Background. Optic disk melanocytoma is a primary tumor of the optic disk that
      represents a clinical diagnostic challenge due to its similarities with melanoma.
      Purpose. The authors present three cases in which genetic expression profiling
      was used to identify tumor prognosis of optic disk melanocytoma. Case Series. In
      two cases fine-needle aspiration biopsy was performed to obtain tissue through a
      transvitreal route into the apex of the tumor while the patient underwent pars
      plana vitrectomy, laser ablation, phacoemulsification with posterior chamber
      intraocular lens implantation, and intravitreal triamcinolone acetonide. In the
      other case the tissue was obtained after definite enucleation. Conclusion.
      Genetic expression profiling is a useful diagnostic tool for classification and
      can provide vital information to the ocular oncologist regarding prognosis. 

PMID- 25984378
TI  - Dynamic Compression of the Spinal Cord by Paraspinal Muscles following Cervical
      Laminectomy: Diagnosis Using Flexion-Extension MRI.
AB  - Introduction. Flexion-extension, or kinematic, MRI has been used to identify
      dynamic spondylotic spinal cord compression not seen with traditional static MRI.
      The use of kinematic MRI to diagnose postoperative complications, specifically
      dynamic compression, is not as well documented. The authors describe a case of
      dynamic spinal cord compression by the paraspinal muscles causing worsening
      myelopathy following cervical laminectomy. This was only diagnosed with flexion
      extension MRI. Methods. The patient was a 90-year-old male presenting to the
      neurosurgery clinic with functional decline and cervical spondylotic myelopathy.
      Results. A multilevel laminectomy was performed. Following surgery the patient
      had progressive weakness and worsening myelopathy. No active cord compression was
      seen on multiple MRIs obtained in a neutral position, and flexion-extension X
      rays did not show instability. A kinematic MRI demonstrated dynamic compression
      of the spinal cord only during neck extension, by the paraspinal muscles. To
      relieve the compression, the patient underwent an instrumented fusion, with cross
      links used to buttress the paraspinal muscles away from the cord. This resulted
      in neurologic improvement. Conclusions. We describe a novel case of spinal cord
      compression by paraspinal muscles following cervical laminectomy. In individuals
      with persistent myelopathy or delayed neurologic decline following posterior
      decompression, flexion-extension MRI may prove useful in diagnosing this
      potential complication. 

PMID- 25984379
TI  - Spectrophotometric Determination of Cr(III) and Pb(II) Using Their Complexes with
      5,11,17,23-Tetra[(2-ethyl acetoethoxyphenyl)(azo)phenyl]calix[4]arene.
AB  - New complexes of 5,11,17,23-tetra[(2-ethyl
      acetoethoxyphenyl)(azo)phenyl]calix[4]arene (TEAC) with Pb(II) and Cr(III) were
      prepared in basic solution with a mixture of MeOH and H2O as solvent. The ratio
      of TEAC and metal ion in complexes was found to be 1 : 1 under investigated
      condition. The complex formation constants (based on Benesi-Hildebrand method)
      for TEAC-Pb(II) and TEAC-Cr(III) were 4.03 * 10(4) and 1.2 * 10(4), respectively.
      Additionally, the molar extinction coefficients were 5 * 10(4) and 1.42 * 10(4)
      for TEAC-Pb(II) and TEAC-Cr(III), respectively. The H-Point Standard Addition
      Method (HPSAM) has been applied for simultaneous determination of complexes
      formation of Cr(III)/Pb(II) and TEAC with concentration from 2 : 1 to 1 : 20
      (w/w). The proposed method was successfully utilized to invest lead and chromium
      contents in plating wastewater samples. The results for several analyzed samples
      were found to be in satisfied agreement with those acquired by using the
      inductively coupled plasma mass spectrometry (ICP-MS) technique. 

PMID- 25984380
TI  - System Characterization of MAHI EXO-II: A Robotic Exoskeleton for Upper Extremity
      Rehabilitation.
AB  - This paper presents the performance characterization of the MAHI Exo-II, an upper
      extremity exoskeleton for stroke and spinal cord injury (SCI) rehabilitation, as
      a means to validate its clinical implementation and to provide depth to the
      literature on the performance characteristics of upper extremity exoskeletons.
      Individuals with disabilities arising from stroke and SCI need rehabilitation of
      the elbow, forearm, and wrist to restore the ability to independently perform
      activities of daily living (ADL). Robotic rehabilitation has been proposed to
      address the need for high intensity, long duration therapy and has shown
      promising results for upper limb proximal joints. However, upper limb distal
      joints have historically not benefitted from the same focus. The MAHI Exo-II,
      designed to address this shortcoming, has undergone a static and dynamic
      performance characterization, which shows that it exhibits the requisite
      qualities for a rehabilitation robot and is comparable to other state-of-the-art
      designs.

PMID- 25984381
TI  - Clinical outcome and cost effectiveness of early tracheostomy in isolated severe
      head injury patients.
AB  - BACKGROUND: Early tracheostomy (ET) has been shown to be effective in reducing
      complications associated with prolong mechanical ventilation. The study was
      carried out to evaluate the role of ET in reducing the duration of mechanical
      ventilation, duration of intensive care unit (ICU) stay, ICU-related morbidities,
      and its overall effect on outcome, in patients with isolated severe traumatic
      brain injury (TBI). METHODS: This 7-year review included 100 ICU patients with
      isolated severe TBI requiring mechanical ventilation. ET was defined as
      tracheostomy within 7 days of TBI, and prolonged endotracheal intubation (EI) as
      EI exceeding 7 days of TBI. Of 100 patients, 49 underwent ET and 51 remained on
      prolong EI for ventilation. All patients were comparable in term of age and
      initial Glasgow Coma Scale (GCS). We evaluated groups regarding clinical outcome
      in terms of ventilator-associated pneumonia (VAP), ICU stay, and Glasgow Outcome
      Score (GOS). RESULTS: The frequency of VAP was higher in EI group relative to ET
      group (63% vs. 45%, P value 0.09). ET group showed significantly less ventilator
      days (10 days vs. 13 days, P value 0.031), ICU stay (11 days vs. 13 days, P value
      0.030), complication rate (14% vs. 18%), and mortality (8.2% vs. 17.6%). Clinical
      outcome assessed on the basis of GOS was also better in the ET group. Total
      inpatient cost was also considerably less (USD $8027) in the ET group compared
      with the EI group (USD $9961). CONCLUSIONS: In patients with severe TBI, ET
      decreases total days of ventilation and ICU stay, and is associated with a
      decrease in the frequency of VAP. ET should be considered in severe head injury
      patients requiring prolong ventilatory support.

PMID- 25984382
TI  - The combined treatment of stenting and surgery in a giant unruptured aneurysm of
      the middle cerebral artery.
AB  - BACKGROUND: This case study reports on a combined therapy of stenting and surgery
      for a giant unruptured middle cerebral artery (MCA) aneurysm with the aim of
      preserving the patency of the vessel during surgery. CASE DESCRIPTION: A 51-year
      old male presented with a sudden onset of moderate left hemiparesis and
      dysarthria. Neuro-radiological evaluations showed a giant right unruptured MCA
      aneurysm without subarachnoid hemorrhage (SAH). The cerebral angiography
      confirmed the presence of such an aneurysm producing compression of both M2
      branches with consequent slowing of the blood flow. Two weeks later, the patient
      underwent the positioning of an Enterprise stent and inside this, a flow diverter
      Silk stent. They were placed across the aneurysm and in one of the two M2
      branches with the aim of protecting them during surgical manipulation. The
      patient went immediately to surgery, where the aneurysm was resected and both M2
      branches decompressed. CONCLUSION: The combined placement of the stents allowed
      safe and successful surgical dissection of the M2 branches and clipping of the
      aneurysm without interrupting the blood flow.

PMID- 25984383
TI  - Endoscopic approaches to brainstem cavernous malformations: Case series and
      review of the literature.
AB  - BACKGROUND: Symptomatic cavernous malformations involving the brainstem are
      frequently difficult to access via traditional methods. Conventional skull-base
      approaches require significant brain retraction or bone removal to provide an
      adequate operative corridor. While there has been a trend toward limited
      employment of the most invasive surgical approaches, recent advances in
      endoscopic technology may complement existing methods to access these difficult
      to reach areas. CASE DESCRIPTIONS: Four consecutive patients were treated for
      symptomatic, hemorrhagic brainstem cavernous malformations via fully endoscopic
      approaches (endonasal, transclival; retrosigmoid; lateral supracerebellar,
      infratentorial; endonasal, transclival). Together, these lesions encompassed all
      three segments of the brainstem. Three of the patients had complete resection of
      the cavernous malformation, while one patient had stable residual at long-term
      follow up. Associated developmental venous anomalies were preserved in the two
      patients where one was identified preoperatively. Three of the four patients
      maintained stable or improved neurological examinations following surgery, while
      one patient experienced ipsilateral palsies of cranial nerves VII and VIII. The
      first transclival approach resulted in a symptomatic cerebrospinal fluid leak
      requiring re-operation, but the second did not. Although there are challenges
      associated with endoscopic approaches, relative to our prior microsurgical
      experience with similar cases, visualization and illumination of the surgical
      corridors were superior without significant limitations on operative mobility.
      CONCLUSION: The endoscope is a promising adjunct to the neurosurgeon's ability to
      approach difficult to access brainstem cavernous malformations. It allows the
      surgeon to achieve well-illuminated, panoramic views, and by combining
      approaches, can provide minimally invasive access to most regions of the
      brainstem.

PMID- 25984384
TI  - Pseudomeningocele formation following chiari decompression: 19-year retrospective
      review of predisposing and prognostic factors.
AB  - BACKGROUND: Pseudomeningocele is a known operative complication of Chiari
      decompression with significant morbidity. METHODS: A retrospective analysis of
      150 consecutive patients from November 1991 to June 2011 was conducted.
      Symptomatic pseudomeningocele was defined clinically; to meet definition it must
      have required operative intervention. Variables evaluated included sex, age, use
      of graft, and use of operative sealant. The Chi-square, Fisher test, and the two
      sample t-test were used as appropriate to determine significance. Multiple
      logistic regression was used to determine independent risk factors for
      complication. RESULTS: A total of 67.3% of patients were female, with average age
      being 39.7 years. A total of 67.3% of patients had a graft placed with the most
      common being fascia lata. Only nine patients (6%) presented with
      pseudomeningocele. Factors observed to be significantly associated with
      pseudomeningocele development were age and use of sealant. Age and sealant use
      were also independent risk factors for complication. Adjusted for the significant
      effect of age, odds for complication among patients with sealant usage were 6.67
      times those for patients without sealant. Adjusted for the significance of
      sealant usage, there is a 6% increase in odds for complication for every year
      increase in patient's age. CONCLUSIONS: A statistically significant relationship
      exists between age and sealant use and the risk of developing a postoperative
      pseudomeningocele. Emphasis and attention must be placed on meticulous closure
      technique. This information can aide in preoperative planning and patient
      selection.

PMID- 25984385
TI  - Infratentorial arteriovenous malformation associated with persistent primitive
      hypoglossal artery.
AB  - BACKGROUND: We report a case of infratentorial arteriovenous malformation (AVM)
      associated with persistent primitive hypoglossal artery (PPHA). To our knowledge,
      this is the second reported case of these combined anomalies in the English
      literature. We discuss the embryological relationship between these two
      congenital vascular anomalies. CASE DESCRIPTION: An 18-year-old girl, who
      suddenly developed severe headache and vomiting followed by loss of
      consciousness, was admitted to our hospital. A computed tomography scan showed
      intracerebellar hemorrhage with obstructive hydrocephalus. Digital subtraction
      angiography revealed an AVM in the left cerebellar hemisphere and an ipsilateral
      PPHA. After the intracranial pressure was stabilized, the AVM was surgically
      removed. AVMs develop during the 4(th) to 8(th) week of embryonic life. In
      contrast, carotid-basilar anastomoses (CBAs) including primitive hypoglossal
      arteries appear and close spontaneously by the 6(th) week of embryonic life.
      Thus, AVMs precede CBAs, and a large amount of blood flows into the adjoining AVM
      via ipsilateral CBAs. As a result, spontaneous closure of a CBA may be disturbed.
      CONCLUSION: We speculate that coexistence of infratentorial AVMs and ipsilateral
      CBAs is not incidental but inevitable.

PMID- 25984386
TI  - Neolithic trepanation decoded- A unifying hypothesis: Has the mystery as to why
      primitive surgeons performed cranial surgery been solved?
AB  - The perplexing mystery of why so many trephined skulls from the Neolithic period
      have been uncovered all over the world representing attempts at primitive cranial
      surgery is discussed. More than 1500 trephined skulls have been uncovered
      throughout the world, from Europe and Scandinavia to North America, from Russia
      and China to South America (particularly in Peru). Most reported series show that
      from 5-10% of all skulls found from the Neolithic period have been trephined with
      single or multiple skull openings of various sizes. The unifying hypothesis
      proposed by the late medical historian Dr. Plinio Prioreschi (1930-2014)
      regarding the reason for these trepanations (trephinations) is analyzed. It is
      concluded that Dr. Prioreschi's cohesive explanation to explain the phenomenon is
      valid and that his intriguing hypothesis is almost certainly correct. In the
      opinion of this author, the mystery within an enigma has been solved. 

PMID- 25984387
TI  - Comparison of equiosmolar concentrations of hypertonic saline and mannitol for
      intraoperative lax brain in patients undergoing craniotomy.
AB  - BACKGROUND: Osmotherapy is the frequently used for the treatment of intracranial
      pressure. The purpose of the study was to compare the effect of equiosmolar
      solution of 3% hypertonic saline and 20% mannitol on brain relaxation in
      supratentorial tumor surgery. METHODS: After institutional review board approval
      and written informed consent, 50 patients aged >18, Glasgow Coma Scale (GCS) >13
      with ASA physical status 1, 2, and 3 scheduled to undergo craniotomy for
      supratentorial tumors were enrolled in this prospective, randomized study.
      Patients received 5 ml/kg of either 3% hypertonic saline (n = 25) or 20% mannitol
      (n = 25). Hemodynamic variables (heart rate [HR], SBP, DBP, MBP, and central
      venous pressure [CVP]), serum electrolytes, serum osmolality, urine output, and
      fluid balance were measured. The surgeon assessed the brain condition on four
      point scale (1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain,
      and 4 = bulging brain), who was blinded to study drug. RESULTS: Brain relaxation
      was comparable in two groups and there was no significant difference (P = 0.633).
      The number of brain conditions classified as perfectly relaxed, satisfactorily
      relaxed, firm brain, and bulging brain in the HS group was 8, 13, 3, and 1,
      respectively, whereas it was 5, 17, 3, and 0, respectively, in the M group. There
      was no significant difference in hemodynamic variables between the two groups
      except CVP at 30 min (P = 048). Compared with mannitol, hypertonic saline caused
      increase in the serum osmolality at 120 min (P = 0.008) and in serum sodium at
      120 min (P = 0.001). Urine output was higher with mannitol than hypertonic saline
      (P = 0.001). CONCLUSION: 3% hypertonic saline and 20% mannitol are equally
      effective for brain relaxation in elective supratentorial tumor surgery and
      compared with mannitol, hypertonic saline was associated with less diuretic
      effect.

PMID- 25984388
TI  - Rare cerebrovascular anomalies in a patient with Cornelia De Lange Syndrome.
AB  - BACKGROUND: Cornelia De Lange (CDL) is a rare genetic syndrome characterized by
      short stature, intellectual disability, skeletal abnormalities, and distinctive
      facial features. We present a case of CDL with several rare cerebrovascular
      anatomic variants that impacted the treatment of a direct cavernous carotid
      fistula (CCF). CASE DESCRIPTION: This 32-year-old male CDL patient suffered a
      direct, traumatic CCF on the left and presented to our institution for
      endovascular management. Cerebral angiography revealed several anatomic variants,
      including hypoplastic external carotid arteries bilaterally. The vascular
      territory typically supplied by the internal maxillary arteries was fed by a
      prominent vessel arising from the internal carotid artery (ICA) in the expected
      location of the vidian artery. This anatomic variant directly impacted management
      due to retrograde filling of the fistula, necessitating coil embolization at its
      origin from the left ICA. CONCLUSION: Advance knowledge of cerebrovascular
      variants associated with CDL may help interventionalists prepare to approach such
      cases. Additionally, further inquiry into the function of proteins encoded by
      genes associated with CDL could better our understanding of vascular development
      in the brain.

PMID- 25984389
TI  - Mini titanium plates and screws for cranial bone flap fixation; an experience
      from Pakistan.

PMID- 25984390
TI  - Diagnosis and evaluation of intracranial arteriovenous malformations.
AB  - BACKGROUND: Ideal management of intracranial arteriovenous malformations (AVMs)
      remains poorly defined. Decisions regarding management of AVMs are based on the
      expected natural history of the lesion and risk prediction for peritreatment
      morbidity. Microsurgical resection, stereotactic radiosurgery, and endovascular
      embolization alone or in combination are all viable treatment options, each with
      different risks. The authors attempt to clarify the existing literature's
      understanding of the natural history of intracranial AVMs, and risk-assessment
      grading scales for each of the three treatment modalities. METHODS: The authors
      conducted a literature review of the existing AVM natural history studies and
      studies that clarify the utility of existing grading scales available for the
      assessment of peritreatment risk for all three treatment modalities. RESULTS: The
      authors systematically outline the diagnosis and evaluation of patients with
      intracranial AVMs and clarify estimation of the expected natural history and
      predicted risk of treatment for intracranial AVMs. CONCLUSION: AVMs are a
      heterogenous pathology with three different options for treatment. Accurate
      assessment of risk of observation and risk of treatment is essential for
      achieving the best outcome for each patient.

PMID- 25984391
TI  - Autologous fibrin sealant (Vivostat((r))) in the neurosurgical practice: Part I:
      Intracranial surgical procedure.
AB  - BACKGROUND: Hemorrhages, cerebrospinal fluid (CSF) fistula and infections are the
      most challenging postoperative complications in Neurosurgery. In this study, we
      report our preliminary results using a fully autologous fibrin sealant agent, the
      Vivostat((r)) system, in achieving hemostasis and CSF leakage repair during
      cranio-cerebral procedures. METHODS: From January 2012 to March 2014, 77 patients
      were studied prospectively and data were collected and analyzed. Autologous
      fibrin sealant, taken from patient's blood, was prepared with the Vivostat((r))
      system and applied on the resection bed or above the dura mater to achieve
      hemostasis and dural sealing. The surgical technique, time to bleeding control
      and associated complications were recorded. RESULTS: A total of 79 neurosurgical
      procedures have been performed on 77 patients. In the majority of cases (98%) the
      same autologous fibrin glue provided rapid hemostasis and dural sealing. No
      patient developed allergic reactions or systemic complications in association
      with its application. There were no cases of cerebral hematoma, swelling,
      infection, or epileptic seizures after surgery whether in the immediate or in
      late period follow-up. CONCLUSIONS: In this preliminary study, the easy and
      direct application of autologous fibrin sealant agent helped in controlling
      cerebral bleeding and in providing prompt and efficient dural sealing with
      resolution of CSF leaks. Although the use of autologous fibrin glue seems to be
      safe, easy, and effective, further investigations are strongly recommended to
      quantify real advantages and potential limitations.

PMID- 25984392
TI  - Recruiting Black Men Who Have Sex with Men and Women (BMSMW) in an Urban Setting
      for HIV Prevention Research.
AB  - OBJECTIVES: Concerns related to stigma and confidentiality limit HIV-related
      study recruitment and retention of Black men who have sex with men and women
      (MSMW). This paper examines lessons learned from recruitment strategies utilized
      in enrolling 437 participants between 2007 and 2011 for a randomized controlled
      trial to test a culturally specific HIV risk-reduction intervention for Black
      MSMW. METHODS: Interested respondents completed a brief screener and participants
      completed surveys at baseline and at post, 3 and 6 months follow-up. Recruitment
      patterns were assessed by examining the source of study information reported when
      respondents were asked how they learned about the study. Chi-square tests were
      then conducted to examine differences in the distribution of participants by self
      reported HIV status, age group and socio-economic status (SES) for each type of
      study information source. RESULTS: Regardless of HIV or SES, study respondents
      were more likely to have received information about the study through a service
      agency than from other sources. Participants ages 30-49 and 50+ years were most
      likely to have learned about the study from an agency (34.9% and 27.0%,
      respectively) or another participant/friend (20.1%, 23.1%) and least likely to
      have found out from bus (0.8%, 0.0%) or radio (1.3%, 0.0%) advertisements;
      whereas younger participants were more likely to have heard about the study
      through a friend/participant (23.4%) than an agency (15.4%). Although, 14.1% of
      participants' ages less than 30 years reported the Internet as their source of
      study information, this compared to just 2.7% and 4.8% for participants in the 30
      49 and 50-plus age groups. CONCLUSIONS: While agencies and referrals from
      personal networks appear to be the most significant recruitment source for
      potential HIV research participants, there is evidence that Internet based tools
      may enhance recruitment, particularly among younger Black MSMW.

PMID- 25984394
TI  - Network-Based Identification of Smoking-Associated Gene Signature for Lung
      Cancer.
AB  - This study presents a novel computational approach to identifying a smoking
      associated gene signature. The methodology contains the following steps: 1)
      identifying genes significantly associated with lung cancer survival, 2)
      selecting genes which are differentially expressed in smoker versus non-smoker
      groups from the survival genes, 3) from these candidate genes, constructing gene
      co-expression networks based on prediction logic for smokers and non-smokers, 4)
      identifying smoking-mediated differential components, i.e., the unique gene co
      expression patterns specific to each group, and 5) from the differential
      components, identifying genes directly co-expressed with major lung cancer
      hallmarks. The identified 7-gene signature could separate lung cancer patients
      into two risk groups with distinct post-operative survival (log-rank P < 0.05,
      Kaplan-Meier analysis) in four independent cohorts (n=427). It also has
      implications in the diagnosis of lung cancer (accuracy = 74%) in a cohort of
      smokers (n=164). Computationally derived co-expression patterns were validated
      with Pathway Studio and STRING 8.

PMID- 25984395
TI  - Systems Approach to Identifying Relevant Pathways from Phenotype Information in
      Dose-Dependent Time Series Microarray Data.
AB  - This study presents a novel computational approach to find relevant pathways from
      dose-dependent time series gene expression data which are significantly
      associated with a phenotype pattern pathological patterns in the comprehensive
      evaluation of database of pathways. Our system uses four steps: 1) identify a set
      of genes which change significantly in dose or time; 2) find phenotype patterns
      and gene coefficients for the genes found in step 1; 3) expand to genome-wide
      coefficients, and 4) identify pathways which are significantly relevant to a
      phenotype pattern. Our technique finds biologically relevant pathways with and
      without phenotype-constraints. Our system has been used on genome-wide expression
      profiles of mouse lungs (n=160) following aspiration of well dispersed multi
      walled carbon nanotubes (MWCNT), in order to detect MWCNT-induced lung
      inflammation and related pathways. The identified significant pathways are
      supported by evidence in the literature and biological validation.

PMID- 25984396
TI  - Another Pill, Another Test, and Another Procedure: One Resident's Reflection on
      Healthcare Cost Containment.
AB  - In the United States, healthcare expenditures have continued to rise at alarming
      rates despite numerous strategies to contain costs. One area of focus that is
      underappreciated is doctor-patient communication about expectations of treatment.
      Studies have shown that clinicians' misperceptions of assumptions about patients'
      expectations are an essential component to our nation's healthcare overuse
      problem. Strategies to address these misperceptions and assumptions as a method
      of reducing costs and providing higher-quality care to our patients are
      warranted. 

PMID- 25984397
TI  - "Perverse incentives" and the triple aim: overcoming the troubled path to
      economic integration for integrative medicine and health.

PMID- 25984393
TI  - S100A12 and the Airway Smooth Muscle: Beyond Inflammation and Constriction.
AB  - Airway inflammation, lung remodeling, and Airway Hyperresponsiveness (AHR) are
      major features of asthma and Chronic Obstructive Pulmonary Disease (COPD). The
      inflammatory response to allergens, air pollutants, and other insults is likely
      to play a key role in promoting structural changes in the lung including the
      overabundance of Airway Smooth Muscle (ASM) seen in asthmatics. These alterations
      or remodeling could, in turn, impact the immunmodulatory actions of the ASM, the
      ASM's contractile properties, and the development of AHR. New evidences suggest
      that airway inflammation and AHR are not tightly related to each other and that
      the structural component of the airway, mainly the ASM, is a chief driver of AHR.
      Members of the S100/calgranulins family have been implicated in the regulation of
      inflammation and cell apoptosis in various systems. S100A12 is highly expressed
      in neutrophils and is one of the most abundant proteins in the lungs of patients
      with asthma or COPD. Studies with genetic engineered mice with smooth muscle cell
      targeted expression of human S100A12 revealed that S100A12 reduces airway smooth
      muscle amounts and dampens airway inflammation and airway hyperreactivity in a
      model of allergic lung inflammation. Thus, targeting airway smooth muscle for
      instance through delivery of pro-apoptotic S100A12 could represent an attractive
      means to promote ASM apoptosis and to reduce ASM abundance in asthmatics.

PMID- 25984398
TI  - Moving the case for equity center stage.

PMID- 25984400
TI  - A Message From Dr Grace Dammann about States of Grace.

PMID- 25984401
TI  - Poem: a lewis Thomas view of medicine.

PMID- 25984399
TI  - Inaugural osher integrative medicine research forum: an overview.

PMID- 25984402
TI  - States of grace: a review.

PMID- 25984403
TI  - The impact of cardiac coherence on executive functioning in children with
      emotional disturbances.
AB  - OBJECTIVE: We used archival data originally collected using a quasi-experimental
      design to analyze inhibition, emotional regulation, working memory, and cognitive
      flexibility before and after an intervention of a coherence training program
      incorporating heart rate variability biofeedback. METHOD: Sixty-three
      participants, ages 7 to 14 years, were involved in the study: 30 in the treatment
      group and 33 in the control group. Split-plot analysis of variance (SPANOVA) was
      used to assess the impact of the intervention for the 4 dependent variables.
      RESULTS: SPANOVA yielded no significant differences among inhibition, emotional
      regulation, working memory, and cognitive flexibility in response to the
      coherence training intervention. CONCLUSIONS: Future research in this area would
      benefit from the use of more objective measures of executive functioning.
      Qualitative assessment of child-reported symptomatology and treatment
      acceptability on the part of students and staff would also be an area for future
      research.

PMID- 25984404
TI  - The effectiveness of a brief mind-body intervention for treating depression in
      community health center patients.
AB  - OBJECTIVE: The objective of this pilot study was to examine the effects of a
      brief, 6-week, 1.5-hour mind-body intervention for depression (MBID) in patients
      being treated for depression in 2 community health centers. DESIGN: The MBID
      taught techniques such as meditation that elicit the relaxation response (RR) in
      combination with additional resiliency-enhancing components. Clinical outcomes of
      24 depressed patients were measured pre-MBID, at completion of MBID, and 3 months
      post-MBID, using the Center for Epidemiological Studies Depression Scale (CES-D
      10), Quality of Life Scale (QoL5), SF-12 Health Survey (SF-12), and Health
      Promoting Lifestyle Profile-II (HPLP-II). RESULTS: Significant post-treatment
      improvements were shown in depressive symptoms, spiritual growth, mental health,
      and quality of life, with a median CES-D 10 change from 17.5 (interquartile ratio
      [IQR] 13.3-22) to 12 (IQR 10-17.5; P<.001); a median HPLP-II Spiritual Growth
      subscale change from 2.0 (IQR 1.8-2.3) to 2.3 (IQR 2.0-3.0; P=.002) and a median
      HPLP-II Stress Management subscale change from 2.0 (IQR 1.8-2.4) to 2.4 (IQR 2.0
      2.9; P=.027); significant improvement in median score on the QoL-5 from 53.3 (IQR
      47.5-62.5) at baseline to 63.3 at endpoint (IQR 50-70; P=.008). Three-month
      follow-up data suggest that the improvement in outcomes were sustained 3 months
      after the intervention. CONCLUSIONS: Participation in a 6-week RR-based MBID is
      associated with an improvement in depression, spiritual growth, and mental health
      among depressed community health center patients.

PMID- 25984405
TI  - Within-team Patterns of Communication and Referral in Multimodal Treatment of
      Chronic Low Back Pain Patients by an Integrative Care Team.
AB  - BACKGROUND: Nonspecific chronic low back pain (CLBP) is a highly prevalent and
      costly public health problem with few treatment options that provide consistent
      and greater than modest benefits. Treatment of CLBP is shifting from unimodal to
      multimodal and multidisciplinary approaches, including biopsychosocially-based
      complementary and integrative care. Multidisciplinary approaches require unique
      levels of communication and coordination amongst clinicians; however, to date few
      studies have evaluated patterns of communication and decision making amongst
      clinicians collaborating in the care of challenging patients with CLBP. METHODS:
      As part of an observational study evaluating the effectiveness and cost
      effectiveness of an integrative, team-based care model for the treatment of CLBP,
      we used multiple qualitative research methods to characterize within-team cross
      referral and communication amongst jointly-trained practitioners representing
      diverse biomedical and complementary disciplines. Patterns of communication and
      coordinated care are summarized for 3 cases of CLBP treated by multiple members
      (>=3) of an integrative medical team embedded within an academic hospital.
      RESULTS: Patients were aged from 36 to 88 years with varied comorbidities.
      Qualitative content analysis revealed 5 emergent themes regarding integrative
      patient care and treatment decision in this clinic: (1) the fundamental
      importance of the clinic's formal teamwork training; (2) the critical
      communicative and collaborative function of regular team meetings; (3) the
      importance to patient care goals of having the varied disciplines practicing
      "under one roof"; (4) a universal commitment to understanding and treating
      patients as whole persons; and (5) a shared philosophy of helping patients to
      help themselves. These key themes are all interconnected and form the foundation
      of the clinic's culture. CONCLUSIONS: Our qualitative findings provide context
      for current trends in enhancing patient-centered, coordinated, and team-based
      care; efforts towards better understanding interprofessional communication;
      overcoming barriers to successful collaboration; and identifying best practices
      for fostering clinical teamwork and a strong team identity. Our findings also
      support the need for further qualitative research, in combination with
      quantitative research, for evaluating the effectiveness and cost-effectiveness of
      resource-intensive integrative models for the treatment of chronic conditions.

PMID- 25984406
TI  - Vision Stations: Addressing Corrective Vision Needs With Low-cost Technologies.
AB  - Eyeglasses, required for functional vision by nearly half the world's population,
      are still needed by more than a billion people. There are a number of constraints
      on the provision of eyeglasses: product cost, durability, and appearance;
      traditional approaches to evaluating refraction; and sustainably scaling
      potential distribution methods. We offer our experience with an immigrant
      population in a US urban setting using a "Vision Station." The station allowed
      for immediate provision of adjustable glasses using self-refraction, ordering of
      custom lenses from a low-cost website, and referral to primary and eye care
      physicians for those with medical eye concerns. As with models in development by
      other groups, Vision Stations connect people with the life-changing provision of
      functional vision. 

PMID- 25984408
TI  - Scanning the global literature.

PMID- 25984407
TI  - Medication-free Alternatives for Long-term Maintenance of Bipolar Disorder: A
      Case Series.
AB  - Psychopharmacological treatment has been the mainstay in long-term maintenance of
      bipolar disorder (BD) patients for the last 60 years. Conventionally accepted
      treatment options are primarily based on expert opinion rather than on well
      executed, independently funded research. Investigation of maintaining patients
      without medications using treatment alternatives has been neglected. This
      clinical case series examines the outcomes of 7 BD patients who experienced a
      poor response or significant side effects with conventional treatment modalities.
      Patients were gradually and safely withdrawn from all medications. Treatment
      strategies were based on an individualized holistic approach using herbs,
      nutritional supplements, vitamins, amino acids, acupuncture, dietary
      recommendations, and behavioral modifications. Multiple treatment modalities were
      combined addressing the etiological causes for BD symptoms. Upon withdrawal from
      psychotropic medications, patients were free of medication-induced side effects
      and obtained psychiatric stability for at least 10 months. Further research is
      needed to investigate the long-term outcomes of BD treatment modalities based on
      well-defined successful outcome criteria, such as reduction in symptoms,
      improvement in quality of life, overall health outcomes, and cost effectiveness. 

PMID- 25984409
TI  - Integrative nursing around the globe.

PMID- 25984410
TI  - Minding the mat: moving the yoga field forward.

PMID- 25984411
TI  - Gazing with soft eyes: envisioning a responsive, integrative healthcare system.

PMID- 25984412
TI  - What is the commitment to interprofessionalism in integrative health and
      medicine?

PMID- 25984413
TI  - Reflection from the artist, virginia daley: art that heals.

PMID- 25984415
TI  - Living in health, harmony, and beauty: the dine (navajo) hozho wellness
      philosophy.
AB  - Hozho is the complex wellness philosophy and belief system of the Dine (Navajo)
      people, comprised of principles that guide one's thoughts, actions, behaviors,
      and speech. The alignment of integrative nursing principles and the Hozho
      Wellness Philosophy illustrates the power that integrative nursing offers as a
      meta-theoretical perspective that can transform our healthcare system so that it
      is inclusive and responsive to the needs of our varied populations. Integrative
      nursing offers the opportunity to re-introduce cultural wellness wisdom, such as
      Hozho, as a means to improve whole-person/whole-systems wellbeing and resilience.
      Integrative nursing, through the acceptance and validation of indigenous health
      sustaining wisdom, contributes to the delivery of effective, authentic,
      culturally tailored, whole-person/whole-system, patient-centered, relationship
      based healthcare. Highlighting the Dine Hozho philosophy re-introduces this
      philosophy to the Dine, other American Indian/Alaska Native nations, global
      indigenous cultures, and even nonindigenous people of the world as a means to
      promote and sustain global health and wellbeing. 

PMID- 25984414
TI  - Yoga adherence in older women six months post-osteoarthritis intervention.
AB  - BACKGROUND/OBJECTIVE: Osteoarthritis (OA) is a highly prevalent condition
      worldwide. Yoga is potentially a safe and feasible option for managing OA;
      however, the extent of long-term yoga adherence is unknown. The purpose of this
      study was to examine yoga adherence 6 months after participants completed an OA
      intervention program. METHODS: This follow-up study employed a cross-sectional
      descriptive design using survey, interview, and video recordings to collect both
      quantitative and qualitative data. A total of 31 participants completed and
      returned the survey, and 10 videotaped their yoga practice for 1 week and
      participated in a face-to-face interview. RESULTS: A majority of participants
      (n=19, 61%) reported that they were still practicing yoga 6 months after the
      intervention program. On average, participants reported practicing 21 to 30
      minutes of yoga per day (32%) 3 to 4 days per week (47%). "Feeling good or
      feeling better after yoga practice" (50%) and "set aside a time" (31%) were the
      most common motivating factors for yoga adherence. Dealing with health problems
      (42%), having pain (25%), and being too busy (25%) were the major barriers.
      Qualitative data revealed that participants: (1) used mindful yoga movement, (2)
      incorporated other forms of exercise and resources during yoga practice, and (3)
      created personalized yoga programs. Additionally, the participants reported less
      OA pain, increased physical endurance, and more relaxation. CONCLUSION: Many
      participants adhered to yoga practice 6 months post-intervention although not at
      the frequency and sequence as prescribed. Feeling better after practice motivated
      participants, but other factors remained key barriers.

PMID- 25984416
TI  - The Gap in Big Data: Getting to Wellbeing, Strengths, and a Whole-person
      Perspective.
AB  - BACKGROUND: Electronic health records (EHRs) provide a clinical view of patient
      health. EHR data are becoming available in large data sets and enabling research
      that will transform the landscape of healthcare research. Methods are needed to
      incorporate wellbeing dimensions and strengths in large data sets. The purpose of
      this study was to examine the potential alignment of the Wellbeing Model with a
      clinical interface terminology standard, the Omaha System, for documenting
      wellbeing assessments. OBJECTIVE: To map the Omaha System and Wellbeing Model for
      use in a clinical EHR wellbeing assessment and to evaluate the feasibility of
      describing strengths and needs of seniors generated through this assessment.
      METHODS: The Wellbeing Model and Omaha System were mapped using concept mapping
      techniques. Based on this mapping, a wellbeing assessment was developed and
      implemented within a clinical EHR. Strengths indicators and signs/symptoms data
      for 5 seniors living in a residential community were abstracted from wellbeing
      assessments and analyzed using standard descriptive statistics and pattern
      visualization techniques. RESULTS: Initial mapping agreement was 93.5%, with
      differences resolved by consensus. Wellbeing data analysis showed seniors had an
      average of 34.8 (range=22-49) strengths indicators for 22.8 concepts. They had an
      average of 6.4 (range=4-8) signs/symptoms for an average of 3.2 (range=2-5)
      concepts. The ratio of strengths indicators to signs/symptoms was 6:1 (range 2.8
      9.6). Problem concepts with more signs/symptoms had fewer strengths. CONCLUSION:
      Together, the Wellbeing Model and the Omaha System have potential to enable a
      whole-person perspective and enhance the potential for a wellbeing perspective in
      big data research in healthcare.

PMID- 25984417
TI  - Optimal healing environments.

PMID- 25984418
TI  - National training and education standards for health and wellness coaching: the
      path to national certification.
AB  - The purpose of this article is twofold: (1) to announce the findings of the job
      task analysis as well as national training and education standards for health and
      wellness coaching (HWC) that have been developed by the large-scale,
      collaborative efforts of the National Consortium for Credentialing Health and
      Wellness Coaches (NCCHWC) and (2) to invite commentary from the public. The rapid
      proliferation of individuals and organizations using the terms of health and/or
      wellness coaches and the propagation of private industry and academic coach
      training and education programs endeavoring to prepare these coaches has created
      an urgent and pressing need for national standards for use of the term health and
      wellness coach, as well as minimal requirements for training, education, and
      certification. Professionalizing the field with national standards brings a clear
      and consistent definition of health and wellness coaching and accepted practice
      standards that are uniform across the field. In addition, clear standards allow
      for uniform curricular criteria to ensure a minimal benchmark for education,
      training, and skills and knowledge evaluation of professional health and wellness
      coaches. 

PMID- 25984419
TI  - Improved clinical outcomes of patients with type 2 diabetes mellitus utilizing
      integrative medicine: a case report.
AB  - This case report demonstrates a successful approach to managing patients with
      type 2 diabetes mellitus (DM2). Botanical herbs (including Gymnema sylvestre) and
      nutrients (including alpha lipoic acid and chromium) were used alongside
      metformin to help improve insulin sensitization; however, the greatest emphasis
      of treatment for this patient centered on a low-carbohydrate, whole-foods diet
      and regular exercise that shifted the focus to the patient's role in controlling
      their disease. Research on DM2 often focuses on improving drug efficacy while
      diet and lifestyle are generally overlooked as both a preventive and curative
      tool. During the 7 months of treatment, the patient's hemoglobin A1c and fasting
      glucose significantly decreased to within normal ranges and both cholesterol and
      liver enzyme markers normalized. A significant body of evidence already exists
      advocating for disease management using various diets, including Mediterranean,
      low-carb, and low-fat vegan diets; however, no clear dietary standards have been
      established. This study supports the use of naturopathic medicine as well as
      dietary and lifestyle changes to develop the most efficacious approach for the
      treatment of DM2. 

PMID- 25984420
TI  - Scanning the global literature.

PMID- 25984421
TI  - Positive Imagery-Based Cognitive Bias Modification as a Web-Based Treatment Tool
      for Depressed Adults: A Randomized Controlled Trial.
AB  - Depression is a global health problem requiring treatment innovation. Targeting
      neglected cognitive aspects may provide a useful route. We tested a cognitive
      training paradigm using positive mental imagery (imagery cognitive bias
      modification, imagery CBM), developed via experimental psychopathology studies,
      in a randomized controlled trial. Training was delivered via the Internet to 150
      individuals with current major depression. Unexpectedly, there was no significant
      advantage for imagery CBM compared with a closely matched control for depression
      symptoms as a whole in the full sample. In exploratory analyses, compared with
      the control, imagery CBM significantly improved anhedonia over the intervention
      and improved depression symptoms as a whole for those participants with fewer
      than five episodes of depression and those who engaged to a threshold level of
      imagery. Results suggest avenues for improving imagery CBM to inform low
      intensity treatment tools for depression. Anhedonia may be a useful treatment
      target for future work.

PMID- 25984423
TI  - Diagnosis of idiopathic pulmonary fibrosis: Current issues.
AB  - Idiopathic pulmonary fibrosis (IPF) accounts for the majority of lung diseases
      classified as idiopathic interstitial pneumonia (IIP). It is considered to be
      lethal because prognosis is very poor and far worse than other types of IIP. An
      early and accurate diagnosis of IPF is critical. The diagnostic process is
      complex and requires a multidisciplinary approach involving a pulmonologist,
      radiologist and pathologist. 

PMID- 25984422
TI  - Quantitative mass spectrometry of urinary biomarkers.
AB  - The effectiveness of treatment of renal diseases is limited because the lack of
      diagnostic, prognostic and therapeutic markers. Despite the more than a decade of
      intensive investigation of urinary biomarkers, no new clinical biomarkers were
      approved. This is in part because the early expectations toward proteomics in
      biomarkers discovery were significantly higher than the capability of technology
      at the time. However, during the last decade, proteomic technology has made
      dramatic progress in both the hardware and software methods. In this review we
      are discussing modern quantitative methods of mass-spectrometry and providing
      several examples of their applications for discovery and validation of renal
      disease biomarkers. We are optimistic about future prospects for the development
      of novel of specific clinical urinary biomarkers.

PMID- 25984424
TI  - Cardiac manifestations in Behcet's disease.
AB  - Behcet's disease (BD) is a chronic inflammatory disorder, with vasculitis
      underlying the pathophysiology of its multisystemic effects. Venous pathology and
      thrombotic complications are hallmarks of BD. However, it has been increasingly
      recognised that cardiac involvement and arterial complications are also important
      aspects of the course of the disease. Cardiac lesions include pericarditis,
      endocarditis, intracardiac thrombosis, myocardial infarction, endomyocardial
      fibrosis, and myocardial aneurysm. Treatment of cardiovascular involvement in BD
      is largely empirical, and is aimed towards suppressing the vasculitis. The most
      challenging aspect seems to be the treatment of arterial aneurysms and thromboses
      due to the associated risk of bleeding. When the prognosis of cardiac involvement
      in BD is not good, recovery can be achieved through oral anticoagulation,
      immunosuppressive therapy, and colchicine use. In this review, we summarise the
      cardiovascular involvement, different manifestations, and treatment of BD. 

PMID- 25984425
TI  - A systematic review of hereditary spherocytosis reported in Chinese biomedical
      journals from 1978 to 2013 and estimation of the prevalence of the disease using
      a disease model.
AB  - Epidemiological information of hereditary spherocytosis in China is slight. This
      systematic review summarizes the number of cases of hereditary spherocytosis
      reported in China Biology Medicine disc from 1978 to 2013. In total, 2,043 cases
      were reported in the past 36 years. We describe its distribution from time and
      space. We also estimate the literature reported prevalence of hereditary
      spherocytosis by DisMod-II software, overall prevalence in China was estimated to
      be: 1.27 cases per 100,000 people in males and 1.49 cases per 100,000 people in
      females. All results suggest a stronger network of diagnosis and treatment
      including all levels of hospitals should be created to improve healthcare for
      hereditary spherocytosis and even other rare diseases in the future, meanwhile we
      can obtain more useful information for orphan drug designation purposes and make
      public health decisions regarding such diseases through the use of the burden of
      disease models. 

PMID- 25984426
TI  - A risk factor analysis on disease severity in 47 premature infants with
      bronchopulmonary dysplasia.
AB  - Bronchopulmonary Dysplasia (BPD) is a rare chronic lung disease and one of the
      most difficult complications to treat in premature infants. With the progress at
      the medical treatment level, an increasing number of BPD premature infants are
      born, meanwhile, they would be at an increasing risk for numerous complications
      and rehospitalization because BPD affects many vital organ systems. The
      pathogenesis of BPD is clearly multifactorial. As the prognosis is closely
      connected with the severity of BPD, early diagnosis and treatment are of great
      help to control the development of BPD. This article focuses on risk factors that
      could influence the severity of BPD in order to provide a reliable basis for
      early diagnosis, treatment, and better patient assessment. 

PMID- 25984427
TI  - Validation of the association of TCF7L2 and SLC30A8 gene polymorphisms with post
      transplant diabetes mellitus in Asian Indian population.
AB  - The rs7903146 and rs13266634 polymorphisms in the TCF7L2 and SLC30A8 genes,
      respectively, have been reported to be associated with type 2 diabetes. However,
      little is known about the association of these polymorphisms with post-transplant
      diabetes mellitus (PTDM). To study this linkage, we determined a distribution of
      allele and genotype frequencies in Asian Indians. 42 PTDM and 98 non-PTDM
      subjects were recruited. Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis was performed to detect for rs7903146 and
      rs13266634 polymorphisms. The clinical details and statistical analysis for PTDM
      and non-PTDM subjects were recorded. Our results observed higher frequencies of
      the minor alleles in rs7903146 and rs13266634 polymorphisms in the PTDM group
      compared to the non-PTDM subjects. The allele frequencies also found to be
      significantly associated with PTDM (rs7903146: T vs C: OR-2.6; (95%CI: 1.2-5.6);
      p = 0.01; rs13266634: T vs C: OR-2.0; (95%CI: 1.1-3.4); p = 0.01). These findings
      suggest that rs7903146 and rs13266634 polymorphisms are associated with PTDM in
      the Asian Indian population despite a relatively small study group. 

PMID- 25984428
TI  - Meconium peritonitis: Prenatal diagnosis of a rare entity and postnatal
      management.
AB  - The aims of this study were to review our therapy and outcome for meconium
      peritonitis (MP) patients, and to clarify predictors of postoperative morbidity
      and mortality. We retrospectively reviewed a total 15 patients with MP who
      received surgical intervention at our institute from December 1990 to November
      2012. Diagnosis of MP was confirmed by operative findings. We analyzed the
      relationship between outcome and patients' factors including patients'
      characteristics, prenatal diagnosis, type of MP, general condition, and surgical
      procedure. There was no relationship between outcome and the following factors:
      gender, gestational age, body weight at birth, delivery type, Apgar score,
      prenatal diagnosis, types and causes of MP, and surgical procedure. However, the
      preoperative presence of circulation deficiency and serum CRP values were
      statistically significant predictors of outcome in our MP patients. Prenatal
      diagnosis is essential for the first step of perinatal therapy for MP. Surgical
      strategy should be selected according to the information of prenatal diagnosis.
      Early surgical procedures to reduce systemic and abdominal inflammation just
      after birth may improve the outcome of severe MP cases. 

PMID- 25984430
TI  - Abdominal pregnancy: Methods of hemorrhage control.
AB  - Abdominal pregnancy is an extremely rare form of ectopic pregnancy, mostly
      occurring secondarily after tubal rupture or abortion with secondary implantation
      anywhere in the peritoneal cavity. Massive intra-abdominal hemorrhage is a life
      threatening complication associated with secondary abdominal pregnancy. Various
      methods and techniques have been reported in the literature for controlling
      hemorrhage. Here, we report a case of massive intraperitoneal haemorrhage
      following placental removal controlled by abdominal packing and review the
      literature for diagnostic and management challenges. 

PMID- 25984429
TI  - Functional recovery after acute intravenous administration of human umbilical
      cord mesenchymal stem cells in rats with cerebral ischemia-reperfusion injury.
AB  - Cell therapy is a potential approach for treatment of strokes. Mesenchymal stem
      cells (MSCs) are a potential cell source for clinical use because they are safe
      and easy to obtain. A peptide solution can promote neural regeneration.
      Previously, such a solution was stereotactically injected into the brain of rats
      with cerebral infarction, resulting in improvement in the animal's neurological
      function and reduction in the infarction volume, but the injury was relatively
      severe. The current study established a rat model of cerebral ischemia
      reperfusion (I/R) injury. MSCs isolated from Wharton's jelly of human umbilical
      cords (HUMSCs) were injected intravenously immediately after cerebral I/R
      injury(3 * 10(6) cells per rat). Twenty-four h and 14 d after surgery, animal
      behavior was evaluated using the Rogers test and infarct lesion volume was
      evaluated by 2,3,5-triphenyltetrazolium chloride staining. Fourteen d after
      surgery, brain tissues were collected at 14 d to study migration/implantation of
      HUMSCs, cellular proliferation, neural regeneration and astrocyte activation.
      Compared to cerebral I/R injury alone, HUMSC treatment improved function at 14 d
      after surgery, with no reduction in infarct volume or migration or implantation
      of cells into the damaged brain areas. Nevertheless, 14 d after surgery, HUMSC
      administration increased cellular proliferation and the level of neurofilament
      200 level and decreased the level of glial fibrillary acidic protein. After
      cerebral I/R injury, acute intravenous administration of HUMSCs could promote
      recovery by activating endogenous neural regeneration and inhibiting astrocyte
      activation, without migration and implantation directly into lesions. 

PMID- 25984431
TI  - Focal mid-ventricular anterior ballooning: An unusual pattern of Takotsubo
      cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TC) or left ventricular apical ballooning syndrome is
      typically characterized by reversible systolic dysfunction of the apical- and mid
      segments of the left ventricle. Symptoms are precipitated by intense emotional or
      physical stress, in the absence of obstructive coronary artery lesions. The most
      common presentation of TC is a transient left ventricular apical ballooning.
      However, recent case reports have described various patterns of TC associated
      with distinct regional left ventricular wall motion abnormalities. One of very
      rare these variants, referred to as a "mid-ventricular" type, is characterized by
      akinesis with or without ballooning of the mid-ventricular segment, together with
      a hyperdynamic base and apex. Using left ventriculography we describe an atypical
      form of TC with transient, focal mid-ventricular ballooning of the anterior
      segment, followed by complete resolution of ballooning, as observed by cardiac
      magnetic resonance (CMR) imaging. 

PMID- 25984432
TI  - Can Hutchinson-Gilford progeria syndrome be cured in the future?
AB  - Progeria is a rare genetic disease that manifests with progressive symptoms
      eventually leading to death. The only current treatment protocol of such patients
      is symptom based. However, recent trials are testing potential and promising
      drugs to treat the underlying genetic mutation and increase life expectancy of
      such patients. 

PMID- 25984433
TI  - Maximizing time from the constraining European Working Time Directive (EWTD): The
      Heidelberg New Working Time Model.
AB  - BACKGROUND: The introduction of the European Working Time Directive (EWTD) has
      greatly reduced training hours of surgical residents, which translates into 30%
      less surgical and clinical experience. Such a dramatic drop in attendance has
      serious implications such compromised quality of medical care. As the surgical
      department of the University of Heidelberg, our goal was to establish a model
      that was compliant with the EWTD while avoiding reduction in quality of patient
      care and surgical training. METHODS: We first performed workload analyses and
      performance statistics for all working areas of our department (operation
      theater, emergency room, specialized consultations, surgical wards and on-call
      duties) using personal interviews, time cards, medical documentation software as
      well as data of the financial- and personnel-controlling sector of our
      administration. Using that information, we specifically designed an EWTD
      compatible work model and implemented it. RESULTS: Surgical wards and operating
      rooms (ORs) were not compliant with the EWTD. Between 5 pm and 8 pm, three ORs
      were still operating two-thirds of the time. By creating an extended work shift
      (7:30 am-7:30 pm), we effectively reduced the workload to less than 49% from 4 pm
      and 8 am, allowing the combination of an eight-hour working day with a 16-hour on
      call duty; thus, maximizing surgical resident training and ensuring patient
      continuity of care while maintaining EDTW guidelines. CONCLUSION: A precise
      workload analysis is the key to success. The Heidelberg New Working Time Model
      provides a legal model, which, by avoiding rotating work shifts, assures quality
      of patient care and surgical training.

PMID- 25984434
TI  - Designing a package of sexual and reproductive health and HIV outreach services
      to meet the heterogeneous preferences of young people in Malawi: results from a
      discrete choice experiment.
AB  - BACKGROUND: This article examines young people's preferences for integrated
      family planning (FP) and HIV services in rural Malawi. Different hypothetical
      configurations for outreach services are presented using a Discrete Choice
      Experiment (DCE). Responses are analysed using Random Parameters Logit and
      Generalised Mixed Logit (GMXL) models in preference space and a GMXL model
      parameterised in willingness-to-pay space. Simulations are used to estimate the
      proportion of respondents expected to choose different service packages as
      elements are varied individually and in combination. RESULTS: Responses were
      collected from 537 young people aged 15-24. Results show that when considering
      attending an outreach service to access family planning young people value
      confidentiality and the availability of HIV services including HIV counselling
      and testing (HCT) and HIV treatment, though significant observable and
      unobservable heterogeneity is present. Female respondents and those aged 20-24
      were less concerned with service confidentiality compared to male respondents and
      those aged 15-19; respondents who were in a relationship at the time of the
      survey valued confidentiality more than those who reported being single. The
      addition of sports and recreation for young people may also be an attractive
      feature of a youth-friendly service; however, preferences for this attribute vary
      according to respondent gender. Results of the simulation modelling indicate that
      the most preferred service package is one that offers confidential services, both
      HCT and HIV treatment and sports for youth, with up to 32% of respondents
      expected to choose this service over a service where clients may have concerns
      over confidentiality, only HCT is available and there are no additional
      activities for young people. Estimates of willingness-to-pay for service
      attributes indicate that respondents were willing to pay up to USD$1.76 for
      confidentiality, USD$0.65 for a service offering both HCT and HIV treatment and
      USD$0.26 for a service including sports for youth. CONCLUSIONS: Young people were
      able to complete a complex DCE and appeared to trade between the different
      characteristics used to describe the outreach services. These findings may offer
      important insight to policy makers designing youth friendly SRH outreach services
      and providers aiming to improve the acceptability and uptake of FP services.

PMID- 25984435
TI  - Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in
      progressive solid tumors.
AB  - BACKGROUND: J591 is a monoclonal antibody that targets the external domain of the
      prostate-specific membrane antigen (PSMA). Besides prostate cancer cells, it also
      targets the neovasculature of non-prostate solid tumors. We provide an analysis
      of the antibody mass-dose dependency of lesion uptake and normal tissue
      retention, together with an assessment of lesion detectability using (111)In-J591
      imaging, compared with conventional imaging in patients with a variety of solid
      tumors. METHODS: Twenty patients in six cohorts received fixed amounts (5, 10,
      20, 40, 60, and 100 mg) of J591 in a phase I trial. A maximum of four
      administrations per patient was given, with each administration separated by 3
      weeks. All antibody administrations included 370 MBq (10 mCi) of (111)In labeled
      to 2 mg of J591 via the chelating agent DOTA. Three whole body (WB) gamma camera
      scans with at least one SPECT scan, along with multiple WB count-rate
      measurements and blood samples, were obtained for all patients. The effect of
      escalating antibody mass on lesion uptake and normal tissue retention was
      evaluated using lesion, liver, serum, and WB residence times and ratios thereof
      for each treatment cycle. Lesion detectability using (111)In-J591 imaging was
      compared to the standard imaging on a lesion-by-lesion basis. RESULTS: A total of
      170 lesions in 20 patients were detected by standard or (111)In-J591 imaging.
      (111)In-J591 targeted both skeletal and soft tissue diseases in all tumor types.
      (111)In-J591 imaging identified 74% (20/27) of skeletal lesions, 53% (18/34) of
      nodes, and 64% (70/109) of other soft tissue/organ lesions. There was increasing
      (111)In-J591 uptake in lesions with increasing antibody mass-dose, coupled with
      decreasing retention in the liver for increments up to 20 mg, and no significant
      change at higher antibody mass. CONCLUSIONS: Radiolabeled J591 antibody has
      potential as a targeting agent for solid tumor vasculature and lesion detection.
      Bone and soft tissue lesions arising from tumors of diverse origin were targeted
      by the anti-PSMA antibody J591. For the detection of lesions in these tumors by
      J591 antibody scans, an antibody mass of 20 mg is adequate. The optimal time of
      imaging is 5 to 7 days post-injection.

PMID- 25984436
TI  - Coma and cerebral imaging.
AB  - The clinical sign of coma is a common feature in critical care medicine. However,
      little information has been put forth on the correlations between coma and
      cerebral imaging methods. The purpose of the article is to compile the available
      information derived from various imaging methods and placing it in a context of
      clinical knowledge of coma and related states. The definition of coma and the
      cerebral structures responsible for consciousness are described; the mechanisms
      of cerebral lesions leading to impaired consciousness and coma are explained.
      Cerebral imaging methods provide a large array of information on the structural
      changes of brain tissue in the various diseases leading to coma. Circumscript
      lesions produce space-occupying masses that displace the brain, ultimately
      leading to various types of herniation. Generalized disease of the brain usually
      leads to diffuse brain swelling which also can cause herniation. Epileptic
      states, however, rarely are detectable by imaging methods and mandate EEG
      examinations. Another important aspect of imaging in coma is the increasing use
      of functional imaging methods, which can detect the function of loss of function
      in various areas of the brain and render information on the extent and severity
      of brain damage as well as on the prognosis of disease. The MRI methods of (1)H
      spectroscopy and diffusion tensor imaging may provide more functional information
      in the future. 

PMID- 25984437
TI  - The protection mechanism of proline from D-galactosamine hepatitis involves the
      early activation of ROS-eliminating pathway in the liver.
AB  - The oral pre-administration of proline, one on the non-essential amino acids, has
      been shown to effectively protect the liver from D-galactosamine (GalN)-induced
      liver injury and dramatically improve the survival rate. In the previous study,
      we reported that protective effect of proline involves the early activation of IL
      6/STAT-3 pathway, an anti-inflammatory and regenerative signaling in the liver.
      Reactive oxygen species (ROS) are mediator of cellular injury and play an
      important role in hepatic damage during GalN-induced hepatitis. The aim of this
      study is to investigate the effect of proline on ROS-eliminating system. The
      activities of major ROS-detoxifying enzymes, i.e., glutathione peroxidase (GP),
      glutathione reductase (GR), catalase, and the level of glutathione in the liver
      were determined. Catalase activity was significantly upregulated in proline group
      from 0 to 3 h after GalN-injection, although GP and GR were downregulated during
      this period, compared with control group. From 6 to 12 h, the level of reduced
      glutathione (GSH) was significantly higher and the ratio of GSH/oxidized
      glutathione (GSSG) tended to be higher in proline group. Consistently with this,
      at 6 h, the GR activity in the proline group was significantly higher, followed
      with the higher tendency of GP activity at 12 h. Catalase activity was also
      significantly higher at 12 h. Taken together, catalase was activated at the
      beginning, followed with the significant activation of glutathione redox system
      around 6 to 12 h in proline group. These results suggest that the elimination of
      ROS in the liver was accelerated in proline group compared with control group at
      the very early stage of GalN-induced hepatitis. 

PMID- 25984438
TI  - Interleukin-6 and microRNA profiles induced by oral bacteria in human atheroma
      derived and healthy smooth muscle cells.
AB  - BACKGROUND: Atherosclerosis is an inflammatory disease with possible
      contributions from bacterial antigens. We aimed to investigate the role of oral
      bacteria as inducers of inflammatory cascades in smooth muscle cells from carotid
      endarterectomy patients (AthSMCs) and healthy controls (HSMCs). FINDINGS:
      Inactivated Streptococcus mitis, S. sanguinis, S. gorgonii, Aggregatibacter
      actinomycetemcomitans and Porphyromonas gingivalis were used to stimulate
      inflammation in HSMCs and AthSMCs. Tumor necrosis factor-alpha (TNFalpha) was
      used as a positive control in all stimulations. Interleukin-6 (IL-6) levels were
      determined from cell culture supernatants and microRNA expression profiles from
      cells after 24 h of bacterial stimulation. Genome wide expression (GWE) analyses
      were performed after 5 h stimulation. All studied bacteria induced pro
      inflammatory IL-6 production in both SMCs. The most powerful inducer of IL-6 was
      A. actinomycetemcomitans (p < 0.001). Of the 84 studied miRNAs, expression of 9
      miRNAs differed significantly (p <= 0.001) between HSMCs and AthSMCs stimulated
      with inactivated bacteria or TNFalpha. The data was divided into two groups: high
      IL-6 producers (A. actinomytectemcomititans and TNFalpha) and low IL-6 producers
      (streptococcal strains and P. gingivalis). The expression of 4 miRNAs (miR-181
      5p, -186-5p, -28-5p and -155-5p) differed statistically significantly (p < 0.001)
      between healthy HSMCs and AthSMCs in the low IL-6 producer group. According to
      multidimensional scaling, two gene expression clusters were seen: one in HSMCs
      and one AthSMCs. CONCLUSIONS: Our results suggest that inactivated oral bacteria
      induce inflammation that is differently regulated in healthy and atherosclerotic
      SMCs.

PMID- 25984439
TI  - Do Social and Economic Policies Influence Health? A Review.
AB  - Although social and economic policies are not considered part of health services
      infrastructure, such policies may influence health and disease by altering social
      determinants of health (SDH). We review social and economic policies in the US
      that have measured health outcomes among adults in four domains of SDH including
      housing and neighborhood, employment, family strengthening/marriage, and income
      supplementation. The majority of these policies target low-income populations.
      These social policies rarely consider health as their initial mission or
      outcomes. When measuring health, the programs document mental health and physical
      health benefits more than half the time, although some effects fade with time. We
      also find considerable segregation of program eligibility by gender and family
      composition. Policy makers should design future social policies to evaluate
      health outcomes using validated health measures; to target women more broadly
      across the socioeconomic spectrum; and to consider family caregiving
      responsibilities as ignoring them can have unintended health effects.

PMID- 25984440
TI  - Adapting Evidence-Based Interventions to Meet the Needs of Adolescents Growing Up
      with HIV in South Africa: The VUKA Case Example.
AB  - The VUKA family program is one of the only evidence-based interventions to
      promote positive psychosocial outcomes in South African HIV-infected pre- and
      early adolescents and their families. In this paper, we discuss the collaborative
      process by which a multidisciplinary team of clinicians, researchers, counselors,
      and artists/educators and families adapted and developed VUKA for this population
      using community-based participatory research methods. We describe the
      intervention and explore lessons learned that may be applicable across contexts
      related to international collaboration and adapting evidence-based interventions
      so that they are likely to be acceptable, feasible, and effective in a given
      setting and country context.

PMID- 25984441
TI  - Cigarette Smoking Disparities among Sexual Minority Cancer Survivors.
AB  - OBJECTIVE: Sexual minority (i.e., lesbian, gay, and bisexual) adults smoke
      cigarettes at higher rates than heterosexual adults. Smoking after receiving a
      cancer diagnosis is a major health concern, yet risk of continued smoking among
      sexual minority cancer survivors is as yet unknown. The current study examines
      current smoking among sexual minority vs. heterosexual adult cancer survivors.
      METHOD: Data drawn from the 2010 Behavioral Risk Factor Surveillance System
      survey in five states (Alaska, California, Massachusetts, New Mexico, and
      Wisconsin) included items about sexual orientation, cancer diagnosis, and tobacco
      use. The analytic sample included 124 sexual minority and 248 propensity score
      matched heterosexual adult cancer survivors. RESULTS: Bivariate analysis showed
      that sexual minority cancer survivors had twice the odds of current smoking as
      their heterosexual counterparts (OR=2.03, 95%CI:1.09-3.80). In exploratory
      analyses stratified by sex, sexual minority disparities in prevalence of smoking
      post-cancer showed a trend toward significance among females, not males.
      CONCLUSION: The current study offers preliminary evidence that sexual minority
      status is one variable among many that must be taken into account when assessing
      health behaviors post-cancer diagnosis. Future research should identify
      mechanisms leading from sexual minority status to increased rates of smoking and
      develop tailored smoking cessation interventions.

PMID- 25984442
TI  - Immunoglobulin isotype isolated from human placental extract does not interfere
      in complement-mediated bacterial opsonization within the wound milieu.
AB  - The wound healing potency of an aqueous extract of placenta can be evaluated
      through the presence of numerous regulatory components. The presence of glycans
      was detected by thin layer chromatography and fluorophore-assisted carbohydrate
      electrophoresis. Mass spectrometric analysis revealed the existence of multiple
      fragments of immunoglobulin G (IgG). IgG was present in the extract at a
      concentration of 25.2 +/- 3.97 MUg/ml. IgG possesses anti-complementary activity
      by diverting the complement activation from target surface. Thus, effect of
      placental IgG on complement-bacteria interaction was investigated through
      classical and alternative pathway and the preparation was ascertained to be safe
      with respect to their interference in the process of bacterial opsonization. 

PMID- 25984443
TI  - Linking the SUMO protease SENP5 to neutrophil differentiation of AML cells.
AB  - In an mRNA profiling screen performed to unveil novel mechanisms of
      leukemogenesis, we found that the sentrin-specific protease 5 (SENP5) was
      significantly repressed in clinical acute myeloid leukemia when compared to
      healthy neutrophil samples. SENP5 is an enzyme that targets and cleaves small
      ubiquitin-like modifier (SUMO) residues from SUMOylated proteins. Further
      investigation with AML neutrophil differentiation cell models showed increased
      SENP5 expression upon induction of differentiation; in contrast, knocking down
      SENP5 resulted in significantly attenuated neutrophil differentiation. Our
      results support a new role of SENP5 in AML pathology, and in particular in the
      neutrophil differentiation of myeloid leukemic cells. 

PMID- 25984444
TI  - Using social media to engage adolescents and young adults with their health.
AB  - We focus on the potential of social media related to the health of adolescent and
      young adults, who are nearly ubiquitous social media users but difficult to
      engage with their health and relatively low healthcare utilizers. Opportunities
      to better engage adolescents and young adults through social media exist in
      healthcare delivery, health education and health policy. However, challenges
      remain for harnessing social media, including making a clear value proposition
      and developing evidence-based frameworks for measuring the impact of social media
      on health.

PMID- 25984445
TI  - Acute lung injury and the role of histones.
AB  - Acute respiratory distress syndrome (ARDS) in humans involves >= 200,000
      individuals in the United States, and has a mortality rate (40%) for which no
      specific drug has been approved for use in humans. We have studied experimental
      acute lung injury (ALI) in mice following airway deposition of bacterial
      lipopolysaccharide (LPS) or the recombinant mouse complement anaphylatoxin, C5a.
      As ALI developed over 6 hr, extracellular histones appeared in bronchoalveolar
      lavage fluids (BALF). Extracellular histone appearance required both C5a
      receptors (C5aR, C5L2) as well as neutrophils (PMNs) and lung macrophages, as
      genetic loss of either C5a receptor or depletion of PMNs or macrophages reduced
      histone levels found in BALF during ALI. It is possible that extracellular
      histones were derived from formation of neutrophil extracellular traps (NETs) in
      lung after PMN contact with C5a. When purified histones were delivered to lung
      via the airways, intense inflammatory injury ensued and type II cells developed
      large blebs indicating cellular damage and apoptosis. Detailed physiological
      measurements revealed severe disruption of blood/alveolar gas exchange. These
      data suggest a key role for histones in development of experimental ALI. 

PMID- 25984447
TI  - Transcriptional profiling of Foxo3a and Fancd2 regulated genes in mouse
      hematopoietic stem cells.
AB  - Functional maintenance of hematopoietic stem cells (HSCs) is constantly
      challenged by stresses like DNA damage and oxidative stress. Foxo factors,
      particularly Foxo3a, function to regulate the self-renewal of HSCs and contribute
      to the maintenance of the HSC pool during aging by providing resistance to
      oxidative stress. Fancd2-deficient mice had multiple hematopoietic defects,
      including HSC loss in early development and in response to cellular stresses
      including oxidative stress. The cellular mechanisms underlying HSC loss in Fancd2
      deficient mice include abnormal cell cycle status, loss of quiescence, and
      compromised hematopoietic repopulating capacity of HSCs. To address on a genome
      wide level the genes and pathways that are impacted by deletion of the Fancd2 and
      Foxo3a, we performed microarray analysis on phenotypic HSCs (Lin-ckit+Sca
      1+CD150+CD48-) from Fancd2 single knockout, Foxo3a single knockout and Fancd2-/
      Foxo3a-/- double-knockout (dKO) mice. Here we provide detailed methods and
      analysis on these microarray data which has been deposited in Gene Expression
      Omnibus (GEO): GSE64215.

PMID- 25984446
TI  - Graph theoretic analysis of structural connectivity across the spectrum of
      Alzheimer's disease: The importance of graph creation methods.
AB  - Graph theory is increasingly being used to study brain connectivity across the
      spectrum of Alzheimer's disease (AD), but prior findings have been inconsistent,
      likely reflecting methodological differences. We systematically investigated how
      methods of graph creation (i.e., type of correlation matrix and edge weighting)
      affect structural network properties and group differences. We estimated the
      structural connectivity of brain networks based on correlation maps of cortical
      thickness obtained from MRI. Four groups were compared: 126 cognitively normal
      older adults, 103 individuals with Mild Cognitive Impairment (MCI) who retained
      MCI status for at least 3 years (stable MCI), 108 individuals with MCI who
      progressed to AD-dementia within 3 years (progressive MCI), and 105 individuals
      with AD-dementia. Small-world measures of connectivity (characteristic path
      length and clustering coefficient) differed across groups, consistent with prior
      studies. Groups were best discriminated by the Randic index, which measures the
      degree to which highly connected nodes connect to other highly connected nodes.
      The Randic index differentiated the stable and progressive MCI groups, suggesting
      that it might be useful for tracking and predicting the progression of AD.
      Notably, however, the magnitude and direction of group differences in all three
      measures were dependent on the method of graph creation, indicating that it is
      crucial to take into account how graphs are constructed when interpreting
      differences across diagnostic groups and studies. The algebraic connectivity
      measures showed few group differences, independent of the method of graph
      construction, suggesting that global connectivity as it relates to node degree is
      not altered in early AD. 

PMID- 25984448
TI  - Appropriateness and diagnostic yield of cardiac magnetic resonance imaging from a
      tertiary referral center in the Middle East.
AB  - PURPOSE: Cardiac magnetic resonance imaging (CMRI) is a novel non-invasive
      modality with many potential indications, and was recently introduced in Lebanon.
      We sought to assess the appropriateness and diagnostic yield of CMR studies
      performed at a tertiary referral center from the Middle East since the inception
      of the program. METHODS: All patients who underwent CMR studies between January
      1(st) 2013 and June 18(th) 2014 were enrolled in this study. CMR reports were
      retrospectively reviewed. The study indication, clinical history, and findings
      were extracted and analyzed. The appropriateness of the study was judged
      according to the 2010 updated Asian Society of Cardiac Imaging guidelines.
      RESULTS: There were a total of 142 patients [mean age 42.1 (SD: 18) years, 24.6%
      females] that underwent CMR study. Two-thirds of studies were performed on an
      outpatient basis, and outside referrals constituted 16.2% of the entire cohort.
      The cardiologists referred 122 cases (86%) with main contribution from
      electrophysiology and imaging specialists. Of the 142 cases, 12 (8.4%) were not
      indicated and added little value. Of the remaining 130 appropriate studies
      (appropriateness level A8-A9), one-third had an incorrect diagnosis prior to CMR,
      and 8% had relevant findings that were missed on other studies but captured by
      CMR. Furthermore, CMR confirmed the diagnosis in 28% of the cases, provided
      relevant information on scar burden, shunt quantification, and ruled out
      infiltrative disease in the remaining patients. Also, CMR demonstrated the
      presence of scar in 45 of patients, among whom 20 (44%) had significant scar
      volume quantification (>5% of left ventricular myocardium). Finally, 9% of
      patients had a relevant extra-cardiac finding that needed further investigation.
      CONCLUSIONS: Despite the recent launch of the CMR program at our institution, the
      majority of studies were appropriately indicated, provided relevant data and were
      clinically useful. Inappropriate or uncertain studies did not provide relevant
      data, and should be further minimized to avoid unnecessary costs and downstream
      testing. Large prospective CMR database with clinical follow-up is needed to
      provide more insight about cardiovascular disease and outcomes in our population.

PMID- 25984449
TI  - Goal attainments and their discrepancies for low density lipoprotein cholesterol
      (LDL-C) and apolipoprotein B (apo B) in over 2,000 Chinese patients with known
      coronary artery disease or type 2 diabetes.
AB  - PURPOSE: Low density lipoprotein cholesterol (LDL-C) is primary treatment target
      for patients with dislipidemia. The apolipoprotein B (apo B), an emerging
      biomarker for cardiovascular risk prediction, appears to be superior to the LDL
      C. However, little is known about goal attainments and their discrepancies for
      LDL-C and apo B in Chinese patients with known CAD or DM. METHODS: A total of
      2,172 hospitalized patients with known coronary artery disease (CAD) or DM, aged
      >27 years of old, were enrolled. The success rates for apo B and LDL-C goal
      attainments were evaluated and compared by categorization and by sex. RESULTS:
      When the success rates for apo B were compared with the ones for LDL-C, the
      former was higher than the latter across all categorizations, with the
      statistically significant differences seen in all patients, CAD alone and DM
      alone (P<0.0001), but not in coexistence of CAD and DM (P=0.190). The trend
      toward to higher success rates for LDL-C and apo B goal attainments in men than
      in women were noteworthy across all categorizations although only in all patients
      and in DM alone patients were the statistically significant differences found
      (P<0.01). CONCLUSIONS: The LDL-C lags behind the apo B in goal attainments in
      Chinese patients. Whether these discrepancies are associated with the occurrence
      differences for CAD and for stroke between the East Asia and the Western
      countries warrants further study.

PMID- 25984450
TI  - Improved non-calcified plaque delineation on coronary CT angiography by sonogram
      affirmed iterative reconstruction with different filter strength and relationship
      with BMI.
AB  - PURPOSE: To prospectively compare non-calcified plaque delineation and image
      quality of coronary computed tomography angiography (CCTA) obtained with sinogram
      affirmed iterative reconstruction (IR) with different filter strengths and
      filtered back projection (FBP). METHODS: A total of 57 patients [28.1% females;
      body mass index (BMI) 29.2+/-6.5 kg/m(2)] were investigated. CCTA was performed
      using 128-slice dual-source CT. Images were reconstructed with standard FBP and
      sinogram-affirmed IR using different filter strength (IR-2, IR-3, IR-4) (SAFIRE,
      Siemens, Germany). Image quality of CCTA and a non-calcified plaque outer border
      delineation score were evaluated by using a 5-scale score: from 1= poor to 5=
      excellent. Image noise, contrast-to-noise ratio (CNR) of aortic root, left main
      (LM) and right coronary artery, and the non-calcified plaque delineation were
      quantified and compared among the 4 image reconstructions, and were compared
      between different BMI groups (BMI <28 and >=28). Statistical analyses included
      one-way analysis of variance (ANOVA), least significant difference (LSD) and
      Kruskal-Wallis test. RESULTS: There were 71.9% patients in FBP, 96.5% in IR-2,
      96.5% in IR-3 and 98.2% in IR-4 who had overall CCTA image quality >=3, and there
      were statistical differences in CCTA exam image quality score among those groups,
      respectively (P<0.001). Sixty-one non-calcified plaques were detected by IR-2 to
      IR-4, out of those 11 (18%) were missed by FBP. Plaque delineation score
      increased constantly from FBP (2.7+/-0.4) to IR-2 (3.2+/-0.3), to IR-3 (3.5+/
      0.3) up to IR-4 (4.0+/-0.4), while CNRs of the non-calcifying plaque increased
      and image noise decreased, respectively. Similarly, CNR of aortic root, LM and
      right coronary artery improved and image noise declined from FBP to IR-2, IR-3
      and IR-4. There were no significant differences of image quality and plaque
      delineation score between low and high BMI groups within same reconstruction (all
      P>0.05). Significant differences in image quality and plaque delineation scores
      among different image reconstructions both in low and high BMI groups (all
      P<0.001) were found. I4f revealed the highest image quality and plaque
      delineation score. CONCLUSIONS: IR offers improved image quality and non
      calcified plaque delineation as compared with FBP, especially if BMI is
      increasing. Importantly, 18% of non-calcified plaques were missed with FBP. IR-4
      shows the best image quality score and plaque delineation score among the
      different IR-filter strength.

PMID- 25984451
TI  - A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from
      stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting
      stent in porcine coronary arteries.
AB  - BACKGROUND: Permanent polymers in first generation drug-eluting stent (DES) have
      been imputed to be a possible cause of persistent inflammation, remodeling,
      malapposition and late stent thrombosis. We aim to describe the in vivo
      experimental result of a new polymer-free DES eluting sirolimus from stent-plus
      balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent
      (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix,
      Biosensors). METHODS: In 10 juvenile pigs, 23 coronary stents were implanted in
      the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day
      follow-up, optical coherence tomography (OCT) and histology were used to evaluate
      neointimal hyperplasia and healing response. RESULTS: According to OCT analysis,
      Focus np stents had a greater lumen area and less neointimal hyperplasia response
      than BMS and Biomatrix had. Histomorphometry results showed less neointimal
      hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition
      in Biomatrix stent compared to Focus np and BMS. CONCLUSIONS: The new polymer
      free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and
      reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28
      day follow-up in this porcine coronary model. This new polymer-free DES is
      promising and warrants further clinical studies.

PMID- 25984452
TI  - Current diagnostic and treatment strategies for Lutembacher syndrome: the pivotal
      role of echocardiography.
AB  - Lutembacher syndrome (LS) is a rare cardiac abnormality characterized by any
      combination of a congenital or iatrogenic atrial septal defect (ASD) and a
      congenital or acquired mitral stenosis (MS). Clinical features and hemodynamic
      effects of LS depend on the balance of effects of the MS and the ASD. Prognosis
      is influenced by several factors [pulmonary vascular resistance, right ventricle
      (RV) compliance, size of ASD and MS severity] but the occurrence of secondary
      pulmonary hypertension and congestive heart failure is commonly associated with
      poor outcome. Echocardiography remains the gold standard for diagnosis and
      evaluation of LS. Timely diagnosis is critical for modifying the natural course,
      by allowing patients to benefit from currently available percutaneous trans
      catheter therapies with favorable effects on the outcomes. This article is a
      review of published literature on the current diagnostic and therapeutic
      modalities for LS, focusing on the pivotal role of echocardiography as the key
      diagnostic tool. Clinical suspicion of LS should prompt extensive investigation
      with non-invasive and where possible, invasive technics. Multicenter registers
      have a potential to assist the evaluation of long term outcomes of percutaneous
      trans-catheter therapies in patients with LS. 

PMID- 25984453
TI  - Spontaneous coronary artery dissection: novel insights on diagnosis and
      management.
AB  - Spontaneous coronary artery dissection (SCAD) remains an elusive and challenging
      clinical entity 8 decades after its initial description. Very recently, our
      understanding of this rare condition has been enriched by data from large series
      of patients prospectively studied and systematically followed. In addition,
      intracoronary diagnostic techniques have provided a new window into the diagnosis
      of this elusive condition of special value in patients presenting with the
      phenotype of intramural hematoma. Spontaneous healing has been demonstrated in
      most patients during long-term follow-up. The large list of associated conditions
      has been recently updated with the novel description of concomitant fibromuscular
      dysplasia (FMD) in large arteries in many of these patients, leading to the
      suggestion of a potential causal link between both conditions. Finally, data from
      large series of patients suggest that, whenever possible, a conservative initial
      management strategy ("watchful waiting"), is indicated in most patients with this
      challenging clinical entity. 

PMID- 25984454
TI  - Traumatic right atrial pseudoaneurysm.
AB  - Pseudoaneurysm is defined as contained blood pooling due to rupture of vascular
      wall. They have higher risk of rupture and hence are usually managed
      aggressively. Trauma, infection and prior surgery are the most common etiologies
      for pseudoaneurysm of most sites. Traumatic cardiac pseudoaneurysm are rare and
      poses a diagnostic challenge to the treating physician since there is no specific
      symptoms associated with pseudoaneurysm and electrocardiogram; cardiac enzymes
      and echocardiogram may be unrevealing or inconclusive in many cases. Cross
      sectional imaging [computed tomography (CT) and magnetic resonance imaging (MRI)]
      is done in cases with high index of suspicion and is the standard modality for
      diagnosis for cardiac pseudoaneurysm. We present a case of conservatively managed
      post-traumatic right atrial pseudoaneurysm with aim to highlight the role of
      electrocardiography (ECG)-gated multidetector computed tomography (MDCT) in
      diagnosis and follow-up of this rare entity that ultimately underwent rapid
      partial thrombosis. 

PMID- 25984455
TI  - Non-identical yet similar: presentation of coronary artery disease in dizygotic
      twins.
AB  - There is a considerable debate regarding the role of genetic and the
      environmental factors in the pathogenesis of coronary artery disease (CAD). Since
      twin pairs are exposed to similar prenatal and postnatal environmental factors, a
      particular role of genetic vs. environmental factors can be evaluated by
      investigating the twins. We report a case of a dizygotic twin-pair who presented
      with simultaneous development of coronary insufficiency, and underwent coronary
      angiography and stent implantation on the same day. There were striking
      similarities and differences in certain characteristics between the presenting
      twins. We believe that the occurrence of CAD might be predetermined genetically,
      while the location of CAD lesion and its severity might be subjected to the
      modification of environmental factors among dizygotic twins. Considering the high
      risk of CAD-related fatal events in monozygotic and dizygotic twins, we recommend
      aggressive medical surveillance for a twin individual, whose co-twin has reported
      a cardiac event. 

PMID- 25984456
TI  - Salt in the wound: (18)F-fluoride positron emission tomography for identification
      of vulnerable coronary plaques.
AB  - Ischaemic vascular events occur in relation to an underlying vulnerable plaque.
      The pathological hallmarks of high-risk plaques are well described and include
      inflammation and microcalcification. To date, non-invasive imaging modalities
      have lacked the spatial resolution to detect these processes with the necessary
      precision to facilitate clinical utility. Positron emission tomography (PET)
      using targeted radiopharmaceuticals affords a highly sensitive tool for
      identifying features of interest and has been in use for several decades in
      oncological practice. Recent developments have created hybrid scanning platforms
      which add the detailed spatial resolution of computed tomography (CT) and, for
      the first time, made imaging of individual coronary plaques feasible. In this
      study we compared the utility of PET-CT using (18)F-fluoride and (18)F
      fluorodeoxglucose ((18)F-FDG) to detect high-risk or ruptured atherosclerotic
      plaques in vivo. (18)F-fluoride localized to culprit and vulnerable plaques as
      determined by a combination of invasive imaging and histological tissue
      examination. In contradistinction, (18)F-FDG analysis was compromised by non
      specific myocardial uptake that obscured the coronary arteries. We discuss the
      findings of this study, the limitations of the current approach of vulnerable
      plaque assessment and some on-going developments in cardiovascular imaging with
      (18)F-fluoride. 

PMID- 25984457
TI  - Hypertrophic cardiomyopathy: still connecting the dots between genotype and
      phenotype.

PMID- 25984458
TI  - Hemodynamic assessment of partial mechanical circulatory support: data derived
      from computed tomography angiographic images and computational fluid dynamics.
AB  - Partial mechanical circulatory support represents a new concept for the treatment
      of advanced heart failure. The Circulite Synergy Micro Pump((r)), where the
      inflow cannula is connected to the left atrium and the outflow cannula to the
      right subclavian artery, was one of the first devices to introduce this concept
      to the clinic. Using computational fluid dynamics (CFD) simulations, hemodynamics
      in the aortic tree was visualized and quantified from computed tomography
      angiographic (CTA) images in two patients. A realistic computational model was
      created by integrating flow information from the native heart and from the
      Circulite device. Diastolic flow augmentation in the descending aorta but
      competing/antagonizing flow patterns in the proximal innominate artery was
      observed. Velocity time curves in the ascending aorta correlated well with those
      in the left common carotid, the left subclavian and the descending aorta but
      poorly with the one in the innominate. Our results demonstrate that CFD may be
      useful in providing a better understanding of the main flow patterns in
      mechanical circulatory support devices. 

PMID- 25984459
TI  - Noninvasive testing strategies in symptomatic, intermediate-risk CAD patients: a
      perspective on the "PROMISE" trial and its potential implementation in clinical
      practice.
AB  - While the results of the Prospective Multicenter Imaging Study for Evaluation of
      Chest Pain trial (PROMISE trial) are negative for the primary outcome, the
      results from this large, contemporary trial of >10,000 patients provide important
      insights into clinical management of patients presenting with chest pain. The
      results reinforce that while diagnostic testing is an important component of
      modern management, its choice should be directed by a clinician in a clinical
      context and with subsequent management in mind. Based on presentation and pre
      test probability, the clinician will decide if any additional testing necessary
      is necessary and if that is the case chose the most appropriate test according to
      current guidelines, applied to the individual patient and clinical scenario. 

PMID- 25984460
TI  - Patient Delay in Accessing Breast Cancer Care in a Sub Saharan African Country:
      Uganda.
AB  - AIMS: To assess patient delay differences between early and late stage breast
      cancer among women in Uganda. STUDY DESIGN: A retrospective analytical study.
      PLACE AND DURATION OF THE STUDY: A study conducted at a tertiary teaching
      hospital. Selected patients' data available for the period between 2008 and 2011
      were included in this study. METHODOLOGY: We included 201 women with
      histologically confirmed breast cancer. The variables analysed included age,
      residence, histological subtype, stage at presentation and time delays. Ethical
      approval was obtained. RESULTS: The mean age for the early and late presenters
      was 49 and 46 years respectively (p=0.065). Rural women were more likely to
      present late. Triple negative breast cancer (TNBC) and HER2+ were the majority
      cancer subtypes for the late presenters. On average women waited for 29 months
      before they presented for specialized cancer treatment (median 12 months; range 1
      120 months). The duration of symptoms didn't differ between the two groups
      (p=0.295) and 75% of early stage presenters, reported at least 6 months after
      noticing symptoms. Only 9% of the TNBC patients presented under 3 months in
      comparison to 14 % for HER2+, 33% for Luminal B and 36% for luminal A. Overall
      23% (39/168) presented with early stage disease. CONCLUSION: Delay in seeking
      appropriate breast cancer care in Uganda was excessive, a sign of a neglected
      disease. Tumor biology factors seem to play a role in late stage presentation.
      Research in factors that lead to prolonged delay in accessing care in a resource
      poor context are needed urgently.

PMID- 25984461
TI  - Global self-rating of oral health as summary tool for oral health evaluation in
      low-resource settings.
AB  - OBJECTIVES: Global Self-Rating of Oral Health (GSROH) has numerous benefits,
      especially in resource-constrained environments with a paucity of dentists
      thereby potentially limiting administration of oral health surveys and monitoring
      of dental treatment. The aim of the study was to identify factors that could
      influence or predict poor self-ratings of oral health. MATERIALS AND METHODS: The
      study was descriptive in design. Data were collected using structured interviewer
      administered questionnaire, which had items on socio-demographic characteristics
      of the respondents and their GSROH. Oral examination was conducted to identify
      untreated dental caries, missing teeth, and mobile teeth. Data were analyzed
      using SPSS, and the P value was set at 0.05. RESULTS: There were 600
      participants; 400 were teachers constituting the non-patient population and 200
      were dental patients with age ranging from 18 to 83 years. A total of 169 (28.1%)
      participants rated their oral health as poor, including 104 patients (52.0%) and
      65 (16.2%) non-patients (P < 0.001). Having had toothache in the preceding 6
      months (62.4% vs. 16.0%, P < 0.001), mobile teeth (46.7% vs. 24.2%, P < 0.001),
      decayed teeth (49.0% vs. 21.3%, P < 0.001), missing teeth (35.0% vs. 26.1%, P =
      0.042), or DMFT score greater than zero (41.1% vs. 20.7%, P < 0.001) was
      associated with poor GSROH. Presence of mobile teeth [odds ratio (OR) = 2.68; 95%
      confidence interval (CI): 1.29, 4.23; P < 0.001] and carious teeth (OR = 2.25;
      95% CI: 1.09, 4.65; P = 0.029) were independent predictors of GSROH. CONCLUSION:
      The GSROH was able to identify individuals with or without oral conditions in the
      studied population, and thus may be used in oral health surveys to assess the
      oral health status and in monitoring of treatment outcome.

PMID- 25984463
TI  - Perception of health care providers toward geriatric oral health in Belgaum
      district: A cross-sectional study.
AB  - OBJECTIVES: To access knowledge and practices related to the oral health of
      geriatrics among the health care providers practicing in urban and rural areas.
      BACKGROUND: Older adults have identified a number of barriers that contribute to
      lack of dental service use. However, barriers that clinicians encounter in
      providing dental treatment to older adults are not as clear-cut. MATERIALS AND
      METHODS: 236 health professionals (of allopathy, ayurveda, and homeopathy) from
      urban and rural areas were assessed by means of structured questionnaire related
      to oral health practices and beliefs. RESULTS: Doctors practicing in urban areas
      assessed dental care needs more frequently (P = 0.038) and performed greater
      practices related to oral health of geriatrics (P = 0.043) than the doctors
      practicing in primary health care (PHC) centers (rural) (P = 0.038). CONCLUSION:
      Owing to the relative lack of knowledge among rural practitioners, there is a
      need to integrate primary health care with oral care in rural areas.

PMID- 25984462
TI  - Oral mucosal lesions in elderly dental patients in Sana'a, Yemen.
AB  - OBJECTIVES: With aging, the oral mucosa becomes more susceptible to external
      stimuli. The aims of this study were to obtain baseline data on the prevalence of
      oral mucosal lesions (OMLs) in a population of elderly Yemeni patients and to
      investigate differences in the presentation of these findings in relation to age,
      gender, education level, and the wearing of dentures. PATIENTS AND METHODS: The
      prevalence of OMLs was assessed by clinical examination of a sample of 310
      elderly Yemeni patients aged 60 years and older. A single examiner performed
      detailed oral examinations of the oral cavity according to international criteria
      and the World Health Organization codes. RESULTS: The overall prevalence of OMLs
      was 77.1%, with a significant difference (P < 0.05) between men (80.3%) and women
      (69.6%). The prevalence rate of OMLs indicated a significant decrease with
      advancing age. The most frequently observed lesions were fissured tongue (34.2%),
      benign tumors (17.1%), hairy tongue (16.5%), and qat-induced white lesions
      (12.6%). Hairy tongue, qat-induced white lesions, and shammah keratosis were
      associated with men (P < 0.01, P < 0.05, and P < 0.05, respectively), whereas
      geographic tongue was associated with women (P < 0.05). The presence of one or
      more lesions was significantly associated with low education level (P < 0.05).
      Certain OMLs showed a significant association with smoking and qat chewing (P <
      0.05). No association was found between the occurrence of OMLs and denture
      wearing (P > 0.05). CONCLUSIONS: The present study has shown a high prevalence of
      oral lesions among Yemeni elders.

PMID- 25984464
TI  - Systemic lycopene as an adjunct to scaling and root planing in chronic
      periodontitis patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Patients with type 2 diabetes have an increased prevalence of
      periodontitis and, in turn, periodontitis adversely affects the diabetic status.
      Oxidative stress plays a key role in affecting the pathophysiology of both the
      diseases and adjunctive systemic antioxidant therapy may have beneficial effect
      on the treatment outcome. This study was planned to compare the efficacy of
      systemic antioxidant therapy with lycopene as an adjunct to scaling and root
      planing versus scaling and root planing alone in chronic periodontitis patients
      with type 2 diabetes mellitus. MATERIALS AND METHODS: 40 diabetic subjects with
      periodontitis, attending the OP wing of the Department of Periodontics of a
      tertiary referral care hospital were randomized and equally divided into group A
      and group B. Diabetes status was recorded as per ADA guidelines and the
      periodontitis status as per American Academy of Periodontology (AAP) guidelines.
      Group A patients underwent scaling and root planing with administration of
      lycopene 8 mg and group B patients were treated with scaling and root planing
      alone. Clinical parameters like gingival index (GI), probing depth (PD), and
      clinical attachment level (CAL) were recorded. Serum markers, i.e.
      malondialdehyde (MDA) (TBARS assay) and C reactive protein (CRP) (ELISA), and
      glycated hemoglobin (HbA1c) levels were assessed at baseline and at 2 months and
      6 months post-therapy. RESULTS: Inter-group comparison showed group A giving
      statistically significant results in reducing mean serum MDA levels at 2 months
      and 6 months, and in reducing mean PD (mm) and mean HbA1c (%) levels at 2 months
      (P < 0.005). CONCLUSION: Lycopene as an adjunctive treatment was effective in
      reducing oxidative stress and restoring altered glycemic levels. Further
      longitudinal studies with a larger sample size are required to establish the role
      of lycopene in the management of chronic periodontitis.

PMID- 25984465
TI  - Age estimation using development of third molars in South Indian population: A
      radiological study.
AB  - AIM: To assess the estimation of chronological age based on the stages of third
      molar development following the eight stages (A-H) method of Demirjian et al. in
      Chennai population of South India. MATERIALS AND METHODS: A sample consisting of
      848 individuals (471 males and 377 females) aged between 14 and 30 years was
      randomly selected for the clinical evaluation and 323 orthopantomograms with
      clinically missing third molars were taken for radiological evaluation using
      Demirjian's method from a Chennai population of known chronological age and sex.
      Statistical analysis was performed using Pearson's Chi-square test and mean
      values were compared between the study groups using t-test or analysis of
      variance (ANOVA) followed by Tukey's highly significant difference (HSD). In the
      present study, P < 0.05 was considered as the level of significance. RESULTS: The
      results showed that the mean age of having clinically completely erupted
      maxillary third molars was 22.41 years in male subjects and 23.81 years in female
      subjects and that of mandibular third molars was 21.49 years in male subjects and
      23.34 years in female subjects. Mandibular third molars were clinically missing
      more often in females than in males. Eruption of mandibular third molars was
      generally ahead of the emergence of maxillary third molars into the oral cavity.
      Third molar development between male and female subjects showed statistically
      significant differences at calcification stage F and stage G in maxillary third
      molars and stage F in mandibular third molars (P < 0.05). CONCLUSION: There are
      differences indicating that maxillary and mandibular third molar eruption reached
      Demirjian's formation stages earlier in males than in females. It is suggested
      that in future studies, to increase the accuracy of age determination,
      indications of sexual maturity and ossification should also be evaluated in
      addition to third molar mineralization.

PMID- 25984466
TI  - Prevalence and characteristics of supernumerary teeth: A survey on 7348 people.
AB  - OBJECTIVE: The aim of the present study was to determine the prevalence of
      supernumerary teeth with by evaluating a large group of adult patients in Turkey
      and to investigate the characteristics of supernumerary teeth with their
      complications and treatment options. STUDY DESIGN: This descriptive and
      retrospective study was carried out in 7348 adult patients aged over 18 years
      (3212 females and 4136 males). The characteristics of the supernumerary teeth
      were noted and the diagnosis was made during clinical and radiographic
      examination with the help of panaromic, periapical, and occlusal radiography.
      Information on the demographic variables for each patient, including age and
      gender, were colleceted. MATERIALS AND METHODS: All supernumerary teeth were
      classfied under several titles such as location, position, morphology, eruption,
      clinical complications, and treatment protocols. The data obtained were subjected
      to statistical analysis. Chi-squared test was used to determine differences in
      distribution of supernumerary teeth when stratified by gender. The statistical
      significance was established by confidence interval of 95% (P <= 0.05). RESULTS:
      123 (2.14%) affected patients (69 females and 54 males) were observed with a
      female:male ratio of 1.28:1 (P < 0.05). One hundred and fifty-six supernumerary
      teeth were detected in all affected patients. CONCLUSION: Supernumerary teeth may
      be observed in adults patients with a similar frequency (2.14%) as in children
      and young adolescents, and clinicians should take measures and examine all
      patients carefully even at older ages.

PMID- 25984467
TI  - Effectiveness of probiotic, chlorhexidine and fluoride mouthwash against
      Streptococcus mutans - Randomized, single-blind, in vivo study.
AB  - AIM: To determine the short-term efficiency of probiotic, chlorhexidine, and
      fluoride mouthwashes on plaque Streptococcus mutans level at four periodic
      intervals. MATERIALS AND METHODS: This was a single-blind, randomized control
      study in which each subject was tested with only one mouthwash regimen. Fifty-two
      healthy qualified adult patients were selected randomly for the study and were
      divided into the following groups: group 1- 10 ml of distilled water, group 2- 10
      ml of 0.2% chlorhexidine mouthwash, group 3- 10 ml of 500 ppm F/400 ml sodium
      fluoride mouthwash, and group 4- 10 ml of probiotic mouthwash. Plaque samples
      were collected from the buccal surface of premolars and molars in the maxillary
      quadrant. Sampling procedure was carried out by a single examiner after 7 days,
      14 days, and 30 days, respectively, after the use of the mouthwash. All the
      samples were subjected to microbiological analysis and statistically analyzed
      with one-way analysis of variance (ANOVA) and post-hoc test. RESULTS: One-way
      ANOVA comparison among groups 2, 3, and 4 showed no statistical significance,
      whereas group 1 showed statistically significant difference when compared with
      groups 2, 3, and 4 at 7(th), 14(th), and 30(th) day. CONCLUSION: Chlorhexidine,
      sodium fluoride, and probiotic mouthwashes reduce plaque S. mutans levels.
      Probiotic mouthwash is effective and equivalent to chlorhexidine and sodium
      fluoride mouthwashes. Thus, probiotic mouthwash can also be considered as an
      effective oral hygiene regimen.

PMID- 25984468
TI  - Effects of non-surgical periodontal therapy on serum lipids and C-reactive
      protein among hyperlipidemic patients with chronic periodontitis.
AB  - AIM: To evaluate the effect of non-surgical periodontal therapy on plasma lipid
      levels in hyperlipidemic patients with chronic periodontitis. MATERIALS AND
      METHODS: After considering the inclusion and exclusion criteria, 30
      hyperlipidemic patients with chronic periodontitis in the age group of 30-70
      years, undergoing treatment in Ahmed Gasim Cardiac and Renal transplant Centre in
      north Sudan were recruited for the study. Patients were randomly assigned to the
      study and control groups. The study group received non-surgical periodontal
      therapy - oral hygiene instructions, scaling and root planing. The control group
      participants received only oral hygiene instructions. Lipid profile [total
      cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL),
      triglycerides (TG)], C-reactive protein (CRP), and periodontal parameters [Plaque
      index (PI), Gingival index (GI), probing pocket depth (PD), and attachment loss
      (ATL)] were measured and compared at baseline and after 3 months of the
      respective intervention. Between-groups analysis was done using independent "t"
      test and within-group analysis was done using dependent "t" test. RESULTS: At
      baseline, groups were comparable based on lipid profile and periodontal
      parameters. After 3 months, the control group showed significant decrease in the
      PI and GI scores while there was no significant change in the other parameters.
      However, the study group showed significant decrease in the LDL and CRP levels
      along with a significant decrease in PD, ATL, PI, and GI scores, compared to the
      baseline values. CONCLUSION: Local non-surgical periodontal therapy resulted in
      improved periodontal health, with significant decrease in the LDL and CRP levels
      in hyperlipidemic patients with chronic periodontitis. Hence, local non-surgical
      periodontal therapy may be considered as an adjunct in the control of
      hyperlipidemia, along with standard care.

PMID- 25984469
TI  - Counterfeit medication: Perception of doctors and medical wholesale distributors
      in western India.
AB  - BACKGROUND: Fake drugs and active pharmaceutical ingredients most often originate
      in emerging industrial economies before entering the global market. Health care
      workers play a crucial role in detecting and preventing the distribution of
      counterfeit medicines. AIM: The present study was conducted to assess the
      knowledge, attitude, and practice of doctors and medicine wholesale distributors
      regarding counterfeit medication in western India. MATERIALS AND METHODS: A cross
      sectional questionnaire survey was conducted among 300 participants consisting of
      100 medical practitioners, 100 dental practitioners, and 100 medical
      storekeepers. RESULTS: It was observed that medical practitioners had more
      knowledge, followed by medical storekeepers and dental practitioners (mean 2.82,
      2.52, and 2.37, respectively). Dental practitioners had the best attitude,
      followed by medical practitioners and wholesale distributors (mean 1.77, 1.76,
      and 1.55, respectively). Best practice behaviors were observed in medical
      storekeepers followed by medical practitioners and dental practitioners (mean
      1.46, 1.29, and 1.12, respectively). CONCLUSION: The study points out the need
      for designing and implementing continuing educational programs and enforcement of
      vigilant laws.

PMID- 25984470
TI  - Antimicrobial effect of calcium hydroxide as an intracanal medicament in root
      canal treatment: a literature review - Part II. in vivo studies.
AB  - The first part of this study reviewed the characteristics of calcium hydroxide
      (Ca(OH)2) and summarized the results of in vitro studies related to its
      antimicrobial effects. The second part of this review covers in vivo studies
      including human clinical studies and animal studies. The use of Ca(OH)2 as an
      intracanal medicament represented better histological results in animal studies.
      However, human clinical studies showed limited antimicrobial effects that
      microorganisms were reduced but not eliminated through the treatment, and that
      some species had resistance to Ca(OH)2. Most of clinical outcome studies
      supported that there is no improvement in healing of periapical lesions when
      Ca(OH)2 was applied between appointments. Further studies are required for the
      antimicrobial effects of Ca(OH)2, and search for the ideal material and technique
      to completely clean infected root canals should be continued. 

PMID- 25984471
TI  - Effect of intracanal medicaments used in endodontic regeneration procedures on
      microhardness and chemical structure of dentin.
AB  - OBJECTIVES: This study was performed to investigate the effects of different
      intracanal medicaments on chemical structure and microhardness of dentin.
      MATERIALS AND METHODS: Fifty human dentin discs were obtained from intact third
      molars and randomly assigned into two control groups and three treatment groups.
      The first control group received no treatment. The second control group (no
      medicament group) was irrigated with sodium hypochlorite (NaOCl), stored in humid
      environment for four weeks and then irrigated with ethylenediaminetetraacetic
      acid (EDTA). The three treatment groups were irrigated with NaOCl, treated for
      four weeks with either 1 g/mL triple antibiotic paste (TAP), 1 mg/mL
      methylcellulose-based triple antibiotic paste (DTAP), or calcium hydroxide
      [Ca(OH)2] and finally irrigated with EDTA. After treatment, one half of each
      dentin disc was subjected to Vickers microhardness (n = 10 per group) and the
      other half was used to evaluate the chemical structure (phosphate/amide I ratio)
      of treated dentin utilizing attenuated total reflection Fourier transform
      infrared spectroscopy (n = 5 per group). One-way ANOVA followed by Fisher's least
      significant difference were used for statistical analyses. RESULTS: Dentin discs
      treated with different intracanal medicaments and those treated with NaOCl + EDTA
      showed significant reduction in microhardness (p < 0.0001) and phosphate/amide I
      ratio (p < 0.05) compared to no treatment control dentin. Furthermore, dentin
      discs treated with TAP had significantly lower microhardness (p < 0.0001) and
      phosphate/amide I ratio (p < 0.0001) compared to all other groups. CONCLUSIONS:
      The use of DTAP or Ca(OH)2 medicaments during endodontic regeneration may cause
      significantly less microhardness reduction and superficial demineralization of
      dentin compared to the use of TAP.

PMID- 25984472
TI  - Evaluation of electrical impedance ratio measurements in accuracy of electronic
      apex locators.
AB  - OBJECTIVES: The aim of this paper was evaluating the ratios of electrical
      impedance measurements reported in previous studies through a correlation
      analysis in order to explicit it as the contributing factor to the accuracy of
      electronic apex locator (EAL). MATERIALS AND METHODS: The literature regarding
      electrical property measurements of EALs was screened using Medline and Embase.
      All data acquired were plotted to identify correlations between impedance and log
      scaled frequency. The accuracy of the impedance ratio method used to detect the
      apical constriction (APC) in most EALs was evaluated using linear ramp function
      fitting. Changes of impedance ratios for various frequencies were evaluated for a
      variety of file positions. RESULTS: Among the ten papers selected in the search
      process, the first-order equations between log-scaled frequency and impedance
      were in the negative direction. When the model for the ratios was assumed to be a
      linear ramp function, the ratio values decreased if the file went deeper and the
      average ratio values of the left and right horizontal zones were significantly
      different in 8 out of 9 studies. The APC was located within the interval of
      linear relation between the left and right horizontal zones of the linear ramp
      model. CONCLUSIONS: Using the ratio method, the APC was located within a linear
      interval. Therefore, using the impedance ratio between electrical impedance
      measurements at different frequencies was a robust method for detection of the
      APC.

PMID- 25984473
TI  - Effect of repetitive pecking at working length for glide path preparation using G
      file.
AB  - OBJECTIVES: Glide path preparation is recommended to reduce torsional failure of
      nickel-titanium (NiTi) rotary instruments and to prevent root canal
      transportation. This study evaluated whether the repetitive insertions of G-files
      to the working length maintain the apical size as well as provide sufficient
      lumen as a glide path for subsequent instrumentation. MATERIALS AND METHODS: The
      G-file system (Micro-Mega) composed of G1 and G2 files for glide path preparation
      was used with the J-shaped, simulated resin canals. After inserting a G1 file
      twice, a G2 file was inserted to the working length 1, 4, 7, or 10 times for four
      each experimental group, respectively (n = 10). Then the canals were cleaned by
      copious irrigation, and lubricated with a separating gel medium. Canal replicas
      were made using silicone impression material, and the diameter of the replicas
      was measured at working length (D0) and 1 mm level (D1) under a scanning electron
      microscope. Data was analysed by one-way ANOVA and post-hoc tests (p = 0.05).
      RESULTS: The diameter at D0 level did not show any significant difference between
      the 1, 2, 4, and 10 times of repetitive pecking insertions of G2 files at working
      length. However, 10 times of pecking motion with G2 file resulted in
      significantly larger canal diameter at D1 (p < 0.05). CONCLUSIONS: Under the
      limitations of this study, the repetitive insertion of a G2 file up to 10 times
      at working length created an adequate lumen for subsequent apical shaping with
      other rotary files bigger than International Organization for Standardization
      (ISO) size 20, without apical transportation at D0 level.

PMID- 25984474
TI  - Effect of resin thickness on the microhardness and optical properties of bulk
      fill resin composites.
AB  - OBJECTIVES: This study evaluated the effects of the resin thickness on the
      microhardness and optical properties of bulk-fill resin composites. METHODS: Four
      bulk-fill (Venus Bulk Fill, Heraeus Kulzer; SDR, Dentsply Caulk; Tetric N-Ceram
      Bulk Fill, Ivoclar vivadent; SonicFill, Kerr) and two regular resin composites
      (Charisma flow, Heraeus Kulzer; Tetric N-Ceram, Ivoclar vivadent) were used.
      Sixty acrylic cylindrical molds were prepared for each thickness (2, 3 and 4 mm).
      The molds were divided into six groups for resin composites. The microhardness
      was measured on the top and bottom surfaces, and the colors were measured using
      Commission Internationale d'Eclairage (CIE) L (*) a (*) b (*) system. Color
      differences according to the thickness and translucency parameters and the
      correlations between the microhardness and translucency parameter were analyzed.
      The microhardness and color differences were analyzed by ANOVA and Scheffe's post
      hoc test, and a student t-test, respectively. The level of significance was set
      to alpha = 0.05. RESULTS: The microhardness decreased with increasing resin
      thickness. The bulk-fill resin composites showed a bottom/top hardness ratio of
      almost 80% or more in 4 mm thick specimens. The highest translucency parameter
      was observed in Venus Bulk Fill. All resin composites used in this study except
      for Venus Bulk Fill showed linear correlations between the microhardness and
      translucency parameter according to the thickness. CONCLUSIONS: Within the
      limitations of this study, the bulk-fill resin composites used in this study can
      be placed and cured properly in the 4 mm bulk.

PMID- 25984475
TI  - Effects of endodontic tri-antibiotic paste on bond strengths of dentin adhesives
      to coronal dentin.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of tri-antibiotic
      paste (TAP) on microtensile bond strengths (MTBS) of dental adhesives to dentin.
      MATERIALS AND METHODS: Sixty extracted molars had their occlusal surfaces
      flattened to expose dentin. They were divided into two groups, i.e., control
      group with no dentin treatment and experimental group with dentin treatment with
      TAP. After 10 days, specimens were bonded using self-etch (Filtek P90 adhesive)
      or etch-and-rinse (Adper Single Bond Plus) adhesives and restored with composite
      resin. Teeth were sectioned into beams, and the specimens were subjected to MTBS
      test. Data were analyzed using two-way ANOVA and post hoc Tukey tests. RESULTS:
      There was a statistically significant interaction between dentin treatment and
      adhesive on MTBS to coronal dentin (p = 0.003). Despite a trend towards worse
      MTBS being noticed in the experimental groups, TAP application showed no
      significant effect on MTBS (p = 0.064). CONCLUSIONS: The etch-and-rinse adhesive
      Adper Single Bond Plus presented higher mean bond strengths than the self-etch
      adhesive Filtek P90, irrespective of the group. The superior bond performance for
      Adper Single Bond when compared to Filtek P90 adhesive was confirmed by a fewer
      number of adhesive failures. The influence of TAP in bond strength is
      insignificant.

PMID- 25984476
TI  - Effect of three different irrigation solutions applied by passive ultrasonic
      irrigation.
AB  - OBJECTIVES: This study evaluated the maximum depth and percentage of irrigant
      penetration into dentinal tubules by passive ultrasonic irrigation (PUI).
      MATERIALS AND METHODS: Thirty extracted human teeth were instrumented and divided
      into three groups. According to final irrigation regimen, 5.25% sodium
      hypochlorite (Group A, NaOCl), 2% chlorhexidine (Group B, CHX) and saline
      solution (Group C, control group) were applied with Irrisafe 20 tips (Acteon) and
      PUI. Irrigant was mixed with 0.1% rhodamine B. Sections at 2 mm, 5 mm, and 8 mm
      from the apex were examined with confocal laser scanning microscopy (CLSM). The
      percentage and maximum depth of irrigant penetration were measured. Kruskal
      Wallis test and Mann-Whitney test were performed for overall comparison between
      groups at each level and for pairwise comparison, respectively. Within a group,
      Wilcoxon test was performed among different levels. p values less than 0.05 were
      considered significant. RESULTS: In all groups, highest penetration depth and
      percentage of penetration were observed at the 8 mm level. At 2 mm level, Groups
      A and B had significantly greater depths and percentages in penetration than
      Group C (p < 0.05), but there were no significant differences between Groups A
      and B. At 5 mm level, penetration depths and percentage of penetration was not
      significantly different among the groups. CONCLUSIONS: NaOCl and CHX applied by
      PUI showed similar depth and percentage of penetration at all evaluated levels.

PMID- 25984477
TI  - Evaluation of penetration depth of 2% chlorhexidine digluconate into root
      dentinal tubules using confocal laser scanning microscope.
AB  - OBJECTIVES: This study evaluated the penetration depth of 2% chlorhexidine
      digluconate (CHX) into root dentinal tubules and the influence of passive
      ultrasonic irrigation (PUI) using a confocal laser scanning microscope (CLSM).
      MATERIALS AND METHODS: Twenty freshly extracted anterior teeth were decoronated
      and instrumented using Mtwo rotary files up to size 40, 4% taper. The samples
      were randomly divided into two groups (n = 10), that is, conventional syringe
      irrigation (CSI) and PUI. CHX was mixed with Rhodamine B dye and was used as the
      final irrigant. The teeth were sectioned at coronal, middle and apical levels and
      viewed under CLSM to record the penetration depth of CHX. The data were
      statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests. RESULTS:
      The mean penetration depths of 2% CHX in coronal, middle and apical thirds were
      138 um, 80 um and 44 um in CSI group, respectively, whereas the mean penetration
      depths were 209 um, 138 um and 72 um respectively in PUI group. Statistically
      significant difference was present between CSI group and PUI group at all three
      levels (p < 0.01 for coronal third and p < 0.001 for middle and apical thirds).
      On intragroup analysis, both groups showed statistically significant difference
      among three levels (p < 0.001). CONCLUSIONS: Penetration depth of 2% CHX into
      root dentinal tubules is deeper in coronal third when compared to middle and
      apical third. PUI aided in deeper penetration of 2% CHX into dentinal tubules
      when compared to conventional syringe irrigation at all three levels.

PMID- 25984478
TI  - The success rate of bupivacaine and lidocaine as anesthetic agents in inferior
      alveolar nerve block in teeth with irreversible pulpitis without spontaneous
      pain.
AB  - OBJECTIVES: Achieving adequate anesthesia with inferior alveolar nerve blocks
      (IANB) is of great importance during dental procedures. The aim of the present
      study was to assess the success rate of two anesthetic agents (bupivacaine and
      lidocaine) for IANB when treating teeth with irreversible pulpitis. MATERIALS AND
      METHODS: Sixty volunteer male and female patients who required root canal
      treatment of a mandibular molar due to caries participated in the present study.
      The inclusion criteria included prolonged pain to thermal stimulus but no
      spontaneous pain. The patients were randomly allocated to receive either 2%
      lidocaine with 1:80,000 epinephrine or 0.5% bupivacaine with 1:200,000
      epinephrine as an IANB injection. The sensitivity of the teeth to a cold test as
      well as the amount of pain during access cavity preparation and root canal
      instrumentation were recorded. Results were statistically analyzed with the Chi
      Square and Fischer's exact tests. RESULTS: At the final step, fifty-nine patients
      were included in the study. The success rate for bupivacaine and lidocaine groups
      were 20.0% and 24.1%, respectively. There was no significant difference between
      the two groups at any stage of the treatment procedure. CONCLUSIONS: There was no
      difference in success rates of anesthesia when bupivacaine and lidocaine were
      used for IANB injections to treat mandibular molar teeth with irreversible
      pulpitis. Neither agent was able to completely anesthetize the teeth effectively.
      Therefore, practitioners should be prepared to administer supplemental anesthesia
      to overcome pain during root canal treatment.

PMID- 25984479
TI  - Use of cone-beam computed tomography and three-dimensional modeling for
      assessment of anomalous pulp canal configuration: a case report.
AB  - Three-dimensional (3D) reconstruction of cone-beam computed tomography (CBCT)
      scans appears to be a valuable method for assessing pulp canal configuration. The
      aim of this report is to describe endodontic treatment of a mandibular second
      premolar with aberrant pulp canal morphology detected by CBCT and confirmed by 3D
      modeling. An accessory canal was suspected during endodontic treatment of the
      mandibular left second premolar in a 21 year old woman with a chief complaint of
      pulsating pain. Axial cross-sectional CBCT scans revealed that the pulp canal
      divided into mesiobuccal, lingual, and buccal canals in the middle third and
      ended as four separate foramina. 3D modeling confirmed the anomalous
      configuration of the fused root with a deep lingual groove. Endodontic treatment
      of the tooth was completed in two appointments. The root canals were obturated
      using lateral compaction of gutta-percha and root canal sealer. The tooth
      remained asymptomatic and did not develop periapical pathology until 12 months
      postoperatively. CBCT and 3D modeling enable preoperative evaluation of aberrant
      root canal systems and facilitate endodontic treatment. 

PMID- 25984480
TI  - Surgical management with intentional replantation on a tooth with palato
      radicular groove.
AB  - A palato-radicular groove (PRG) is a developmental anomaly primarily found in the
      maxillary lateral incisors. It is a potential communication path between the root
      canal and the periodontium that decreases the survival prognosis of the affected
      tooth, therefore compromising the stability of the dental structure in the oral
      cavity. The aim of this case report is to present an original technique where a
      PRG was treated by means of intracanal disinfection, PRG sealing with glass
      ionomer, replantation with intentional horizontal 180 degree rotation of the
      tooth, and an aesthetic veneer placed to provide adequate tooth morphology. The
      clinical and biological benefits of this novel technique are presented and
      discussed. 

PMID- 25984481
TI  - Statistical notes for clinical researchers: post-hoc multiple comparisons.

PMID- 25984482
TI  - Treatment after bleaching for optimal bonding.

PMID- 25984483
TI  - Cultural roles of native patient navigators for american Indian cancer patients.

PMID- 25984484
TI  - A new era for Journal of Biological Research-Thessaloniki.

PMID- 25984485
TI  - Aquatic animal resources in Prehistoric Aegean, Greece.
AB  - This paper explores the early stages in the history of fishing in the Aegean Sea
      in Greece, and highlights its formative phases and its specific characteristics
      in different points in time. This is testified by various physical remains, such
      as fish bones, fishing tools, and representations in art, which are gathered in
      the course of archaeological research. The aquatic resources in the Aegean Sea
      have been exploited and managed for millennia by communities that lived near the
      water and often made a living from it. The earliest evidence for a systematic,
      intensive exploitation of marine resources in the Aegean Sea dates to the
      Mesolithic, eleven millennia ago. In the Neolithic period, the adoption of a
      sedentary, agro-pastoral way of life led to a reduction in the intensity of
      fishing and shellfish gathering. Its importance as an economic resource remained
      high only in certain regions of rich, eutrophic waters. In the Bronze Age, an era
      of social complexity and centralized economy, the exploitation of aquatic, mostly
      marine, resources became a complex, multi-faceted activity which involved
      subsistence, industry and ideology. The range of preferred fish and invertebrate
      species, the fishing technology, and the processing of fish and shellfish in
      order to produce elaborate foods or prestige items are all traceable aspects of
      the complex relationship between humans and the aquatic resources throughout the
      prehistory of fishing and shellfish gathering in the Aegean area. The broadening
      of collaboration between archaeology and physical sciences offers new means to
      explore these issues in a more thorough and nuanced manner. 

PMID- 25984486
TI  - Reproducibility and reliability assays of the gene expression-measurements.
AB  - BACKGROUND: Reliability and reproducibility are key metrics for gene expression
      assays. This report assesses the utility of the correlation coefficient in the
      analysis of reproducibility and reliability of gene expression data. RESULTS: The
      correlation coefficient alone is not sufficient to assess equality among sample
      replicates but when coupled with slope and scatter plots expression data equality
      can be better assessed. Narrow-intervals of scatter plots should be shown as a
      tool to inspect the actual level of noise within the data. Here we propose a
      method to examine expression data reproducibility, which is based on the ratios
      of both the means and the standard deviations for the inter-treatment expression
      ratios of genes. In addition, we introduce a fold-change threshold with an inter
      replicate occurrence likelihood lower than 5% to perform analysis even when
      reproducibility is not acceptable. There is no possibility to find a perfect
      correlation between transcript and protein levels even when there is not any post
      transcriptional regulatory mechanism. We therefore propose an adjustment for
      protein abundance with that of transcript abundance based on open reading frame
      length. CONCLUSIONS: Here, we introduce a very efficient reproducibility
      approach. Our method detects very small changes in large datasets which was not
      possible through regular correlation analysis. We also introduce a correction on
      protein quantities which allows us to examine the post-transcriptional regulatory
      effects with a higher accuracy.

PMID- 25984487
TI  - Expression of relative-protein of hypoxia-inducible factor-1alpha in
      vasculogenesis of mouse embryo.
AB  - BACKGROUND: Physiological vasculogenesis in embryonic tissues share some
      important features with pathological neoangiogenesis in tumors. Linearly
      Patterned Programmed Cell Necrosis (LPPCN) and Vasculogenic Mimicry (VM) have
      been reported in tumors. The term VM refers to the aggressive tumor cells with
      CD31-negative phenotype to form Periodic Alphacid Schiff (PAS)-positive network,
      that mimics the pattern of embryonic vasculogenic networks. LPPCN had been
      observed in our laboratory, and served as a spatial infrastructure for VM and
      endothelium-dependent vessel formation. Studies have been shown that hypoxia
      inducible factor-1alpha (HIF-1alpha) can induce tumor cells to form vessel-like
      tubes and express genes associated with VM. Therefore, an analogous investigation
      has been carried out to determine if these patterns existed in mouse embryonic
      vasculogenesis. RESULTS: In this essay, the results demonstrated that the number
      of Linearly Patterned Cell Alphapoptosis (LPCA), embryo Vasculogenic MUimicry
      (embryo VM), endothelium-dependent vessels, and relative-protein of HIF-1alpha
      expression all showed time-dependent tendencies on E5.5-E9.5 (p < 0.05). The
      proteins CD133, VEGF, Twist, E-cadherin, and Vimentin showed local plexus
      distribution on E6.5-E7.5 (p < 0.05). CONCLUSIONS: LPCA and embryo VM existed in
      embryonic vasculogenesis. The relative protein of HIF-1alpha regulated the mouse
      embryonic vasculogenesis.

PMID- 25984488
TI  - First insights on the mitochondrial genetic variability of Lightiella magdalenina
      (Crustacea), the sole Mediterranean cephalocarid species.
AB  - BACKGROUND: Here we report the first insight into the mitochondrial (Cytochrome c
      Oxidase subunit I - COI and Cytochrome b - Cyt b) genetic variation of the only
      Mediterranean cephalocarid Lightiella magdalenina. FINDINGS: COI sequences
      provide a scenario of low intraspecific variability, while significant genetic
      divergence occurs between L. magdalenina and L. incisa. Interestingly, Cyt b
      sequences reveal a higher degree of intraspecific variability, with no shared
      haplotypes between the sites considered. CONCLUSIONS: In the future, COI and Cyt
      b molecular markers could be used as valuable tools to shed new light into the
      extant species within the genus Lightiella thus providing molecular support to
      the taxonomical identifications carried out on a morphological basis.

PMID- 25984489
TI  - An overview: biomolecules from microalgae for animal feed and aquaculture.
AB  - Despite being more popular for biofuel, microalgae have gained a lot of attention
      as a source of biomolecules and biomass for feed purposes. Algae farming can be
      established using land as well as sea and strategies can be designed in order to
      gain the products of specific interest in the optimal way. A general overview of
      the contributions of Algae to meet the requirements of nutrients in
      animal/aquaculture feed is presented in this study. In addition to its
      applications in animal/aquaculture feed, algae can produce a number of
      biomolecules including astaxanthin, lutein, beta-carotene, chlorophyll,
      phycobiliprotein, Polyunsaturated Fatty Acids (PUFAs), beta-1,3-glucan, and
      pharmaceutical and nutraceutical compounds which have been reviewed with respect
      to their commercial importance and current status. The review is further extended
      to highlight the adequate utilization of value added products in the feeds for
      livestock, poultry and aquaculture (with emphasis in shrimp farming). 

PMID- 25984490
TI  - Effects of the two carvone enantiomers on soil enzymes involved in the C, P, and
      N cycles.
AB  - BACKGROUND: Essential oils exert stimulatory or inhibitory effects on the size
      and activity of the soil microbial communities. Given that microbial biomass is
      the main source of soil enzymes, in this study, we examined how R-(-)- and S-(+)
      carvone affect the activity of dehydrogenase, urease, and alkaline phospho
      monoesterase, and the overall microbial activity, as expressed by soil
      respiration. Enzymatic and microbial activities were recorded every week, for a
      period of four weeks, during which the two carvone enantiomers were added twice,
      with a two-week interval, into soil samples. For all dependent variables, we
      analysed the deviations of the experimental from control values. RESULTS:
      Treatment per se had a significant effect only on urease. Its activity was
      inhibited in the S-carvone samples, while it was enhanced or inhibited, depending
      on the time of incubation, in the R-carvone ones. The activity of alkaline
      phospho-monoesterase was not affected by S-carvone, but it increased with R
      carvone. Soil respiration markedly increased in presence of the two carvones with
      highest values being recorded in the R-carvone samples. None of the temporal
      patterns of the three enzymes' activity followed the pattern of soil respiration.
      CONCLUSIONS: The significant treatment by time interactions for the activities of
      all three enzymes indicates that responses are not consistent over time; this
      suggests differently functioning or structured microbial communities. Given their
      differing effects on soil enzymes, these compounds and the aromatic plants
      bearing them could find use in sustainable agriculture for the control of soil
      enzymes and, hence, the soil processes that they are associated with.

PMID- 25984491
TI  - Renin-angiotensin system gene polymorphisms among Saudi patients with coronary
      artery disease.
AB  - BACKGROUND: The polymorphisms in the components of the renin-angiotensin system
      (RAS) are important in the development and progression of coronary artery disease
      (CAD) in some individuals. Our objectives in the present investigation were to
      determine whether three RAS polymorphisms, angiotensin-converting enzyme
      insertion/deletion (ACE I/D), angiotensin receptor II (Ang II AT2 - C3123A) and
      angiotensinogen (AGT-M235T), are associated with CAD in the Saudi population. We
      recruited 225 subjects with angiographically confirmed CAD who had identical
      ethnic backgrounds and 110 control subjects. The polymerase chain reaction
      restriction fragment length polymorphisms (RFLP) technique was used to detect
      polymorphisms in the RAS gene. RESULTS: Within the CAD group, for the ACE I/D
      genotype, DD was found in 64.4%, 26.3% carried the ID genotype, and 9.3% carried
      the II genotype. Within the control group, the DD genotype was found in 56.4%,
      23.6% carried the ID genotype, and 20% carried the II genotype. The odds ratio
      (OR) of the ACE DD vs II genotype with a 95% confidence interval (CI) was 2.45
      (1.26-4.78), with p = 0.008. For the Ang II AT2 receptor C3123A genotype, within
      the CAD group, CC was found in 39.6%, 17.8% carried the CA genotype, and 42.6%
      carried the AA genotype. Within the control group, CC was found in 39.1%, 60.9%
      carried the CA genotype, and there was an absence of the AA genotype. The OR of
      the Ang II AT2 receptor C3123A CC vs AA genotypes (95% CI) was 0.01, with p =
      0.0001. A significant association with CAD was shown. For the AGT-M235T genotype,
      within the CAD group, MM was found in 24.0%, 43.6% carried the MT genotype and
      32.4% carried the TT genotype. Within the control group, MM was found in 26.4%,
      45.5% carried the TT genotype and 28.2% carried the MT genotype. The OR of MM vs
      TT (95% CI) was 0.79 (0.43 to 1.46), which was insignificant. CONCLUSIONS: There
      is an association between the ACE I/D and Ang II AT2 receptor C3123A
      polymorphisms and CAD, however, no association was detected between the AGT M235T
      polymorphism and CAD in the Saudi population.

PMID- 25984492
TI  - The native flora of Mountain Panachaikon (Peloponnese, Greece): new records and
      diversity.
AB  - BACKGROUND: This study presents the native flora of Mountain Panachaikon (N.W.
      Peloponnese, Greece), after extensive field work (from ~700 to 1900 m) and
      critical literature review. RESULTS: The vascular native flora of Mt. Panachaikon
      comprises 757 taxa, 95 of which are Greek endemics, 79 are Balkan endemics, while
      229 taxa are reported here for the first time. The known distribution of the
      Greek endemics Alyssum montanum subsp. montanum var. graecum, Carum heldreichii,
      Cirsium heldreichii, Genista milii, Minuartia eurytanica and Seseli parnassicum
      is expanded, being reported for the first time for the floristic region of
      Peloponnese, and the number of the known populations of the Near Threatened
      Gymnospermium altaicum subsp. peloponnesiacum is increased. CONCLUSIONS: The
      study area appears to have the second highest endemism and the highest one in W.
      Greece, compared with other mountains of N. Peloponnese and Sterea Ellada, while
      22.10% of the endemics are protected and/or evaluated as Near Threatened to
      Endangered. It also exhibits a rather high proportion of Balkan endemics, in
      relation to its geographic location, and some genuine arctic-alpine taxa. These
      indicate that Mt. Panachaikon can be rendered as a plant diversity hotspot in the
      Peloponnese.

PMID- 25984493
TI  - Benthic molluscan macrofauna structure in heavily trawled sediments (Thermaikos
      Gulf, North Aegean Sea): spatiotemporal patterns.
AB  - BACKGROUND: Spatio-temporal patterns on benthic molluscan macrofauna structure
      and function (feeding guilds) were investigated in a commercial fishing ground in
      Thermaikos Gulf (N Aegean Sea). Fishery management measures in this area include
      a trawling period of 8 months per year (October to May). Macrofauna samples were
      collected before and after 30 and 120 days of the commencement of the trawling
      period (temporal axis) along a southward transect (spatial axis) and down through
      the sediment profile (vertical axis). RESULTS: Main results revealed no
      recognizable changes in community diversity and structure at temporal scales.
      This finding can probably be attributed to the fact that the examined communities
      are subjected to continuous disturbances deriving from multiple natural and
      anthropogenic stressors acting simultaneously in Thermaikos Gulf. Molluscan
      assemblages were already stressed before the commencement of the trawling period,
      indicating that the time period in which bottom trawling is prohibited is not
      sufficient for the recovery of benthic communities. Significant shifts in the
      trophic structure of molluscan assemblages were also detected. The direct
      mortality of herbivorous species and the loss of filter feeding organisms may be
      attributed to the passage of the fishing gear and to sediment re-suspension,
      respectively. Trawling disturbance may have created the observed vertical
      patterns of the community structure since hauling induces profound changes in the
      geochemical profile of the sediment. CONCLUSIONS: Our findings sustained the
      notion that bottom trawling, alongside with other types of human induced
      stressors, can have considerable effects on the structure and function of the
      benthic domain. Therefore, our results highlighted the need of an Ecosystem Based
      Fishery Management (EBFM) perspective in Thermaikos Gulf to ensure both fisheries
      and ecosystem sustainability.

PMID- 25984494
TI  - In the wild hybridization of annual Datura species as unveiled by morphological
      and molecular comparisons.
AB  - BACKGROUND: The present work aimed to verify whether intermediate variants were
      natural crosses between Datura species (D. stramonium forms and D. ferox). Their
      existence has been long ago insinuated but has not been studied using
      morphological features and molecular tools. The variants differed in stem
      coloring, upper bearing forks, and fruit characters. RESULTS: Principal
      Components Analysis of 11 morphological characteristics showed that D. ferox and
      D. stramonium (forms stramonium and tatula) were quite different and the putative
      hybrids were intermittent. The D. ferox * D. stramonium f. tatula was closer to
      the latter of its parents. Sequencing analysis revealed identical amplified trnL
      intron in all variants and a 100% homology with D. stramonium accession number
      EU580984.1 suggested that this plastid cannot discern Datura variants. However,
      genomic analysis with URP markers indicated that the hybrids had >60% genetic
      makeup similarity with both parents suggesting that the intermediate variants
      were putative inter-specific hybrids. Moreover, the dendrogram stemmed from
      cluster analysis of the fingerprint profile of variants placed D. stramonium and
      D. ferox in different branches indicating their genetic differentiation from each
      other as well as from their hybrids. CONCLUSIONS: The findings suggest that the
      natural hybridization of annual Datura species occurs. Extrapolating, this
      hybridization could be the first step for speciation. More possibly, it can alter
      population composition, its weediness and adaptability to local conditions.

PMID- 25984496
TI  - Gametogenic cycle of Crassostrea gigas in contrasting Mediterranean habitats:
      marine (Gulf of Tunis) and continental (Bizert lagoon) culture sites.
AB  - BACKGROUND: The gametogenic cycle of Crassostrea gigas, a species imported into
      the Mediterranean for aquaculture, has been studied (May 2005 to July 2006) in
      two contrasting habitats of Tunisia: the Bizert lagoon, where oyster farms have
      been developed since 1970, and the Gulf of Tunis, where oysters have been
      experimentally farmed during this study, to assess the potential of this latter
      marine area for sustaining oyster-culture. RESULTS: The sexual cycle of the
      species was described through the histological examination of the gonads, the
      estimation of oocytes diameter, and the assessment of its condition and gonadal
      condition indices. The applied techniques gave similar results. The gametogenic
      cycle of C. gigas was precocious and more intense in oysters farmed within the
      lagoon than in the marine area, considering as well gonadal growth, maturation
      stages and gametes release. CONCLUSIONS: The obtained results are probably
      related with the different environmental conditions of the studied habitats,
      temperature and food supply, in particular. The sexual cycle of the species was
      successfully completed in the marine area, stressing the invasive character of C.
      gigas.

PMID- 25984495
TI  - Movements of a juvenile Crowned Eagle (Harpyhaliaetus coronatus) tracked by
      satellite telemetry in central Argentina.
AB  - BACKGROUND: A juvenile Crowned Eagle was tagged at its nest with a satellite
      transmitter. The Crowned Eagle (Harpyhaliaetus coronatus) is one of the most
      unknown raptor species from the American continent. Their current distribution
      ranges from central Brazil to central Argentina, with a total population of 350
      1500 individuals across this large area, being thus largely fragmented. RESULTS:
      During the three years of tracking the bird concentrated its movements in a range
      spanning for 12845 km(2), but concentrating mainly in four smaller areas
      accounting for 3073 km(2). The locations were recorded mainly over shrubland
      habitats (86.5%), whereas other habitats used were different types of mosaics
      that included cropland and natural vegetation (forest, shrubland or grassland)
      close to wetlands. CONCLUSIONS: The home-range estimated for this individual
      during the whole period was 12845 km(2) (according to 95% fixed kernel). However,
      the bird concentrated most of its movements in smaller areas (as defined above),
      that accounted for a total of 3073 km(2) (50% fixed kernel). During these three
      years, most of the locations of the juvenile solitary Crowned Eagle were recorded
      over shrubland habitats (86.5% of the locations). Understanding in a more
      detailed way the juvenile ranging behaviour and habitat preferences would be of
      great importance for the conservation of the Crowned Eagle.

PMID- 25984497
TI  - Use of the comet assay technique for quick and reliable prediction of in vitro
      response to chemotherapeutics in breast and colon cancer.
AB  - BACKGROUND: Determination of response to chemotherapy is a major requirement of
      personalized medicine. Resistance, whether developed or native, critically
      affects a treatment's success. Single Cell Gel lectrophoresis - also known as a
      comet assay - is used to detect DNA damage at the level of individual eukaryotic
      cells. We assessed the use of comet assays in determining response to
      chemotherapeutic drugs that are widely used in breast and colon cancer. RESULTS:
      We treated human breast and colon cancer cell lines with melphalan, cisplatin,
      mechlorethamine or doxorubicin, as monotherapies. Drug activities varied even in
      the same cancer types, further demonstrating the heterogeneity of different
      cancer types. CONCLUSION: The comet assay technique can provide reliable and
      quick results with minimum requirements and is applicable to a wide variety of
      drugs.

PMID- 25984498
TI  - Effect of mixotrophic growth on the ultrastructure and fatty acid composition of
      the diatom Synedra acus from Lake Baikal.
AB  - BACKGROUND: Interest in studies concerning the effect of organic carbon sources
      on the growth of diatoms is largely aimed at subsequent physiological changes
      occurring in their cells. There are no data on structural changes in the
      cytoplasm and their relationship with changes in the composition of fatty acids
      in the course of mixotrophic culturing of freshwater diatoms. To elucidate the
      role of lipids in the growth of diatom cells in autotrophic and mixotrophic
      cultures, it is necessary to obtain information on the distribution of fatty
      acids among intracellular compartments and on possible ultrastructural changes in
      the cells. RESULTS: In this study, the results demonstrated that Synedra acus
      cells cultured in the presence of 80 mM glycerol contained lipid bodies of
      increased size, while cells from cultures supplemented with 40 mM glucose
      accumulated polysaccharide (chrysolaminarin) granules. An increase in the
      relative amounts of palmitic and stearic acids was revealed at the exponential
      growth phase of S. acus in the medium with 80 mM glycerol, which was indicative
      of the accumulation of fatty acids contained in triacylglycerols. CONCLUSIONS:
      Synedra acus subsp. radians have an ability to proliferate in the presence of
      high concentrations of organic substances and their transport into cells is
      evidence for its high adaptation potential, which, along with other factors,
      accounts for the dominance of this diatom in the spring-summer plankton of the
      oligotrophic Lake Baikal.

PMID- 25984499
TI  - Comparing the two Greek archipelagos plant species diversity and endemism
      patterns highlight the importance of isolation and precipitation as biodiversity
      drivers.
AB  - BACKGROUND: Greece has two island archipelagos, the Aegean and the Ionian, which
      host a rich array of plants and wildlife, particularly endemic and threatened
      plant species. Despite the long history of island biogeographic studies in the
      Aegean, similar studies in the Ionian remain limited, with the two island
      archipelagos rarely being compared. RESULTS: The Aegean and Ionian archipelagos
      share many features, especially regarding total plant diversity, but exhibit
      different patterns of endemism. For instance, when considering similarly sized
      islands, those in the Ionian host as many as, if not more, species compared to
      the Aegean. In contrast, the Ionian Islands are poor in endemics (particularly
      narrow range endemics, such as single island or regional endemics) and threatened
      taxa, compared to the Aegean Islands. In the Ionian, endemics only persist on the
      largest islands, and form a very small proportion of the species pool, compared
      to the Aegean archipelago. CONCLUSIONS: The lack of endemism might be attributed
      to the more recent separation of the Ionian Islands from the mainland and the
      shorter distance separating them from the mainland. In addition, the Ionian
      Islands receive higher levels of precipitation and are typically covered by
      denser and higher vegetation than the Aegean Islands. These conditions favour
      greater total species richness, but tend to lead to higher numbers of common
      species compared to threatened and endemic taxa. This study demonstrates that
      both isolation and precipitation serve as biodiversity drivers, influencing plant
      species diversity and endemism patterns, of the two Greek archipelagos.

PMID- 25984500
TI  - Correction: in the wild hybridization of annual datura species as unveiled by
      morphological and molecular comparisons.

PMID- 25984502
TI  - New gastropod records for the Eastern Mediterranean Sea and one new alien
      (Emarginula decorata Deshayes, 1863) for the Mediterranean Sea from NW Aegean
      Sea, Greece.
AB  - BACKGROUND: The NW Aegean Sea has a complex topography, high quality waters,
      oligotrophic to eutrophic conditions, is connected with estuaries and wetlands,
      is of high ecological interest, harbours all the types of human activities and
      yet few researchers work on its marine biodiversity. With this study, the
      contribution to the knowledge of the Hellenic and Eastern Mediterranean gastropod
      biodiversity of the studied families is continued, and an expansion of the search
      in other substrates and deeper waters of the NW Aegean Sea with emphasis on the
      minor in size species during the period from October 2008 to January 2014.
      RESULTS: Thirty seven species belonging to seven families (Cerithiopsidae,
      Fissurellidae, Phasianellidae, Scissurellidae, Siliquariidae, Skeneidae, and
      Triphoridae) were identified and their biodiversity was compared with the current
      checklists of marine gastropod molluscs for the Hellenic Seas based on previous
      surveys. In this collection of gastropods, one species (Emarginula decorata
      Deshayes, 1863) is a new alien for the Mediterranean Sea, 14 species are new for
      the Eastern Mediterranean Sea and 16 species are new for the Hellenic fauna (with
      the one above mentioned alien species included). The main identification
      characteristics and ecological information such as habitat, distribution, alien
      expansion paths to the NW Aegean Sea and origin of the species are given and
      discussed. CONCLUSIONS: The Hellenic gastropod biodiversity of the studied
      families was enriched with 37 new records for the N Aegean Sea, out of which 16
      are new for Greece, 14 are new for the Eastern Mediterranean Sea while one
      (Emarginula decorata) is a new alien for the Mediterranean Sea.

PMID- 25984501
TI  - Antioxidant effect of a polyphenol-rich grape pomace extract on motility,
      viability and lipid peroxidation of thawed bovine spermatozoa.
AB  - BACKGROUND: Grape extracts of the Greek species Vitis vinifera possess potent
      antioxidant properties in vitro. The freeze/thaw process and the preparation of
      semen during assisted reproductive techniques can adversely affect the functional
      integrity of spermatozoa. The objective was to assess the effect of three
      different concentrations (1 MUg ml(-1), 2 MUg ml(-1) and 5 MUg ml(-1)) of a
      polyphenol-rich grape pomace extract on motility, viability, acrosomal and lipid
      peroxidation status of thawed bovine spermatozoa after 2 and 4 hrs of incubation.
      RESULTS: The results indicate that the percentage of "Rapid" spermatozoa remained
      significantly increased (p <0.05) in the presence of 5 MUg ml(-1) of the extract,
      compared to the control after 2 hrs of incubation. Additionally, the incubation
      of spermatozoa with 2 MUg ml(-1) and 5 MUg ml(-1) of the extract for 2 hrs
      resulted in a significantly better maintenance of viable spermatozoa with intact
      acrosome (p <0.05). The other parameters did not show statistically significant
      changes. Moreover, the presence of 2 MUg ml(-1) and 5 MUg ml(-1) of the extract
      kept the levels of Malondialdehyde (MDA) production in significantly lower level,
      compared to the other groups, after 2 hrs and 4 hrs of incubation (p <0.05).
      Particularly, a dose-dependent effect was noticed after 2 hrs of incubation.
      CONCLUSIONS: Our results suggest that the grape pomace extract exerts a powerful
      antioxidant role, by suppressing lipid peroxidation, and provides protection in
      terms of motility and acrosomal integrity, which are correlated with in vivo
      fertility. The optimal extract concentration is 5 MUg ml(-1).

PMID- 25984503
TI  - A review of the biology of Australian halophilic anostracans (Branchiopoda:
      Anostraca).
AB  - Australia has two species of Artemia: A. franciscana introduced to salt works and
      apparently not spreading, and parthenogenetic Artemia presently spreading widely
      through southwestern Australia. In addition, and unique to Australia, there are
      18 described species of Parartemia in hypersaline lakes. All Parartemia use a
      lock and key mechanism in amplexus and hence have distinctive antennal-head
      features in males and thoracic modifications in females. Various factors,
      including climatic fluctuations and isolation, contribute to a far higher
      diversity in the southwest of the continent. There are few congeneric occurrences
      of Parartemia possibly due to their consuming largely uniform allochthonous
      organic matter rather than multisized planktonic algae. In P. zietziana there are
      2-3 cohorts a year each persisting 3-9 months. Up to 80% of assimilation is used
      in respiration and at times energy balance is negative, which accounts for its
      continuous mortality, inconsistent growth rates and unpredictable recruitment.
      Many species are as osmotically competent as Artemia, but are at a disadvantage
      in hypersaline waters >250 g L(-1) as they lack the haemoglobin of Artemia.
      Parartemia acidiphila and P. contracta live in markedly acid waters to pH 3.5,
      where dissolved carbonate and bicarbonate are unavailable, and hence they must
      have evolved an additional proton pump to produce ATP from endogenous CO2.
      Occurrences of some species have been severely curtailed by lake salinisation
      (which includes acidification and changes in hydroperiod), so that their
      continued existence is in doubt. A few species of the otherwise freshwater
      Branchinella occur in mainly hyposaline waters. 

PMID- 25984504
TI  - Cell culture, sex determination and single cell cloning of ovine transgenic
      satellite cells in vitro.
AB  - BACKGROUND: This study was performed to describe the basic methods to isolate and
      culture of primary satellite cells (PSCs) obtained from 50 to 60-day-old sheep
      fetuses, single cell cloning of transfected PSCs and sexing of ovine PSCs based
      on the ZFY/ZFX, amelogenin and high-motility-group (HMG) box sequences. RESULTS:
      Three-step enzymatic digestion method increased PSCs isolation from tissue and
      reduced the damage of cells during long time incubation with enzymes. The results
      of cloning showed that the 103 and 81 clones (from a total of 184 clones) were
      derived from feeder and bFGF treatment, respectively. The overall sexing
      efficiency in the present study was 100%. Southern blot results of sex
      determination were in complete agreement with PCR-amplified bands which confirmed
      that the HMG box of SRY gene amplified from the ovine genome and that was
      specific for male. CONCLUSIONS: We successfully isolated and cultured sheep
      primary satellite cells via mechanical and enzymatic disaggregation. Our finding
      demonstrated that use of feeder and addition of bFGF to the culture medium
      improved cloning efficiency. The results of sex detection demonstrated that these
      methods can be applied to detect the sex of primary satellite cells and to
      determine the sex of sheep embryo prior to produce sheep embryos by somatic cell
      nuclear transfer technique in vitro. Nevertheless, our findings suggested that
      sex determination of satellite cells base on amelogenin sequence can be accurate,
      relatively simple, rapid, and inexpensive.

PMID- 25984505
TI  - The ecology of Dunaliella in high-salt environments.
AB  - Halophilic representatives of the genus Dunaliella, notably D. salina and D.
      viridis, are found worldwide in salt lakes and saltern evaporation and
      crystallizer ponds at salt concentrations up to NaCl saturation. Thanks to the
      biotechnological exploitation of D. salina for beta-carotene production we have a
      profound knowledge of the physiology and biochemistry of the alga. However,
      relatively little is known about the ecology of the members of the genus
      Dunaliella in hypersaline environments, in spite of the fact that Dunaliella is
      often the main or even the sole primary producer present, so that the entire
      ecosystem depends on carbon fixed by this alga. This review paper summarizes our
      knowledge about the occurrence and the activities of different Dunaliella species
      in natural salt lakes (Great Salt Lake, the Dead Sea and others), in saltern
      ponds and in other salty habitats where members of the genus have been found. 

PMID- 25984506
TI  - Antimicrobial residual effects of irrigation regimens with maleic acid in
      infected root canals.
AB  - BACKGROUND: The success of endodontic treatment depends largely on the control of
      microorganisms present in infected root canals. The aim of this study was to
      determine the residual antimicrobial activity of several final irrigation
      protocols with 7% maleic acid (MA) alone and combined with chlorhexidine (CHX),
      cetrimide (CTR) or both, in root canals infected with Enterococcus faecalis.
      Biofilms of E. faecalis were grown in uniradicular roots for 4 weeks. A total of
      72 specimens were divided into 5 experimental groups according to the final
      irrigation regime used: Group 1: 2.5% NaOCl; Group 2: 7% MA; Group 3: 7% MA +
      0.2% CTR; Group 4: 7% MA + 2% CHX; Group 5: 7% MA + 0.2% CTR + 2% CHX; and
      CONTROL GROUP: 0.9% saline solution. Twelve roots (2/group) that were
      instrumented and not infected served as negative or sterility controls. The
      proportion of ungrown samples over 60 days was evaluated using non-parametric
      Kaplan-Meier survival analysis. Differences among groups were tested using the
      log-rank test (p< 0.05). RESULTS: The association of MA with CHX and CHX + CTR as
      final irrigating solutions showed the best results, 5 and 4 samples out of 12,
      respectively, and without differences between them (p = 0.928), followed by 7% MA
      + 0.2% CTR with 7 out of 12. The 7% MA (11/12) group showed significant
      differences with respect to the groups in which MA was combined with CHX (p <
      0.005) and CHX + CTR (p < 0.005). CONCLUSION: Final irrigating solutions of 7% MA
      combined with 2% CHX or 2% CHX + 0.2% CTR were found to effectively improve
      antimicrobial root canal disinfection.

PMID- 25984507
TI  - Paralia (Bacillariophyta) stowaways in ship ballast: implications for
      biogeography and diversity of the genus.
AB  - BACKGROUND: The genus Paralia Heiberg is one of the most recognizable, widely
      distributed and commonly reported diatoms from contemporary coastal marine
      environments and ship ballast. Species discovery has historically been made in
      diatoms through the recognition of morphological discontinuities between
      specimens, first using light and later electron microscopy. However, recently,
      morphologically semi-cryptic species of Paralia were delineated using genetic
      analyses, among mostly tropical and subtropical sites. RESULTS: Ten morphological
      characters of the frustules and sequence fragments from the nuclear genome
      (conserved 18S regions of ribosomal RNA and the variable internal transcribed
      spacer [ITS]), and from the RuBisCo large subunit (rbcL) gene of the chloroplast
      genome were examined. Frustule morphology did not segregate species, however,
      comparisons of sequence fragments and ITS2 secondary structures yielded a new
      species from North American waters, P. guyana (with four genodemes), and another
      widely-distributed species, P. marina. The latter was lecto- and epitypified here
      because it is most similar to specimens in the type preparation BM1021
      representing Smith's concept of the species. Paralia marina and certain genodemes
      of P. guyana were morphologically cryptic. Only those genodemes of P. guyana that
      possess prickly separation valves could be morphologically distinguished from P.
      marina with relative confidence in SEM preparations. All clones established from
      chains isolated from the ballast sediment of the ships sailing along the Atlantic
      coast of North America belonged to P. guyana. All DNA sequences of preserved
      Paralia chains recovered from the three trans-Atlantic voyages (TAVs) samples
      arriving to eastern Canada from Europe shared 100% identity with P. marina.
      CONCLUSION: First, if the [Formula: see text] = 130592 P. marina cells per
      ballast tank at the end of the TAVs represents their abundance in ballast tanks
      of similar crossings and following mid-ocean ballast water exchange, then this
      diatom, if de-ballasted, exerts a strong and continued propagule pressure on
      Eastern Canadian coasts. Despite this, as of 2009, P. marina was found only in
      Cheticamp, Nova Scotia, Canada. Second, genetic analysis readily segregated
      cryptic and semi-cryptic taxa of Paralia, highlighting the usefulness of the
      molecular approach to species recognition, e.g., in programs monitoring alien
      introductions.

PMID- 25984508
TI  - Assessment of the microbiological quality of fresh produce on sale in Sicily,
      Italy: preliminary results.
AB  - BACKGROUND: Fresh produce occupies an increasingly important place in the human
      food supply because of its health-promoting nutritional properties. Most fresh
      produce is eaten raw or after minimal processing and, consequently, pathogen
      contamination can represent a serious health risk. There has been an increase in
      foodborne outbreaks and cases associated with fresh produce, but literature data
      about the prevalence of pathogen contamination are inconsistent. This study was
      undertaken to assess the hygienic quality and the prevalence of the most common
      bacterial pathogens in fresh produce sold in retail markets in Sicily. A total of
      125 samples of different types of vegetables were examined by standardized
      microbiological methods. RESULTS: The aerobic mesophilic count ranged between 2
      log and 7 log cfu g(-1) and the Enterobacteriaceae counts between < 1 log and 6
      log cfu g(-1), with statistically significant differences between unprocessed and
      minimally processed products (p < 0.05). Escherichia coli was detected only in
      leaf vegetables at a concentration of 2 log - 3 log cfu g(-1). Enterococci were
      found at a concentration of 2 log - 4 log cfu g(-1). Coagulase positive
      Staphylococci and sulphite-reducing Clostridia were not detected in any sample.
      Three samples tested positive for Listeria monocytogenes, Yersinia enterocolitica
      and Salmonella veneziana. CONCLUSION: Our study provides updated data on the
      microbiological quality of retail vegetables and confirms the need to implement
      strategies to increase microbial safety of fresh produce.

PMID- 25984510
TI  - EvidenceToPrograms.com: A Toolkit to Support Evidence-Based Programming for
      Seniors.

PMID- 25984509
TI  - Development of a Custom-Designed, Pan Genomic DNA Microarray to Characterize
      Strain-Level Diversity among Cronobacter spp.
AB  - Cronobacter species cause infections in all age groups; however neonates are at
      highest risk and remain the most susceptible age group for life-threatening
      invasive disease. The genus contains seven species:Cronobacter sakazakii,
      Cronobacter malonaticus, Cronobacter turicensis, Cronobacter muytjensii,
      Cronobacter dublinensis, Cronobacter universalis, and Cronobacter condimenti.
      Despite an abundance of published genomes of these species, genomics-based
      epidemiology of the genus is not well established. The gene content of a diverse
      group of 126 unique Cronobacter and taxonomically related isolates was determined
      using a pan genomic-based DNA microarray as a genotyping tool and as a means to
      identify outbreak isolates for food safety, environmental, and clinical
      surveillance purposes. The microarray constitutes 19,287 independent genes
      representing 15 Cronobacter genomes and 18 plasmids and 2,371 virulence factor
      genes of phylogenetically related Gram-negative bacteria. The Cronobacter
      microarray was able to distinguish the seven Cronobacter species from one another
      and from non-Cronobacter species; and within each species, strains grouped into
      distinct clusters based on their genomic diversity. These results also support
      the phylogenic divergence of the genus and clearly highlight the genomic
      diversity among each member of the genus. The current study establishes a
      powerful platform for further genomics research of this diverse genus, an
      important prerequisite toward the development of future countermeasures against
      this foodborne pathogen in the food safety and clinical arenas. 

PMID- 25984511
TI  - Full-range public health leadership, part 1: quantitative analysis.
AB  - BACKGROUND: Workforce and leadership development are central to the future of
      public health. However, public health has been slow to translate and apply
      leadership models from other professions and to incorporate local perspectives in
      understanding public health leadership. PURPOSE: This study utilized the full
      range leadership model in order to examine public health leadership.
      Specifically, it sought to measure leadership styles among local health
      department directors and to understand the context of leadership in local health
      departments. METHODS: Leadership styles among local health department directors
      (n = 13) were examined using survey methodology. Quantitative analysis methods
      included descriptive statistics, boxplots, and Pearson bivariate correlations
      using SPSS v18.0. FINDINGS: Self-reported leadership styles were highly
      correlated to leadership outcomes at the organizational level. However, they were
      not related to county health rankings. Results suggest the preeminence of leader
      behaviors and providing individual consideration to staff as compared to
      idealized attributes of leaders, intellectual stimulation, or inspirational
      motivation. IMPLICATIONS: Holistic leadership assessment instruments such as the
      multifactor leadership questionnaire can be useful in assessing public health
      leaders' approaches and outcomes. Comprehensive, 360-degree reviews may be
      especially helpful. Further research is needed to examine the effectiveness of
      public health leadership development models, as well as the extent that public
      health leadership impacts public health outcomes.

PMID- 25984512
TI  - Dual mode antibacterial activity of ion substituted calcium phosphate
      nanocarriers for bone infections.
AB  - Nanotechnology has tremendous potential for the management of infectious diseases
      caused by multi-drug resistant bacteria, through the development of newer
      antibacterial materials and efficient modes of antibiotic delivery. Calcium
      phosphate (CaP) bioceramics are commonly used as bone substitutes due to their
      similarity to bone mineral and are widely researched upon for the treatment of
      bone infections associated with bone loss. CaPs can be used as local antibiotic
      delivery agents for bone infections and can be substituted with antibacterial
      ions in their crystal structure to have a wide spectrum, sustained antibacterial
      activity even against drug resistant bacteria. In the present work, a dual mode
      antibiotic delivery system with antibacterial ion substituted calcium deficient
      hydroxyapatite (CDHA) nanoparticles has been developed. Antibacterial ions such
      as zinc, silver, and strontium have been incorporated into CDHA at concentrations
      of 6, 0.25-0.75, and 2.5-7.5 at. %, respectively. The samples were found to be
      phase pure, acicular nanoparticles of length 40-50 nm and width 5-6 nm
      approximately. The loading and release profile of doxycycline, a commonly used
      antibiotic, was studied from the nanocarriers. The drug release was studied for 5
      days and the release profile was influenced by the ion concentrations. The
      release of antibacterial ions was studied over a period of 21 days. The ion
      substituted CDHA samples were tested for antibacterial efficacy on Staphylococcus
      aureus and Escherichia coli by MIC/MBC studies and time-kill assay. AgCDHA and
      ZnCDHA showed high antibacterial activity against both bacteria, while SrCDHA was
      weakly active against S. aureus. Present study shows that the antibiotic release
      can provide the initial high antibacterial activity, and the sustained ion
      release can provide a long-term antibacterial activity. Such dual mode antibiotic
      and antibacterial ion release offers an efficient and potent way to treat an
      incumbent drug resistant infection. 

PMID- 25984513
TI  - Escherichia coli Isolated from Urinary Tract Infections of Lebanese Patients
      between 2005 and 2012: Epidemiology and Profiles of Resistance.
AB  - The early treatment of urinary tract infections (UTIs) is directly related to
      decrease in morbidity, which makes the empirical treatment of great importance.
      Recently, beta lactamases of several types have emerged as significant mechanisms
      of resistance in Gram-negative bacilli, especially Escherichia coli. Our aim was
      to study the urinary E. coli isolated from Lebanese patients and to characterize
      their mechanisms of resistance. The study analyzed data between 2005 and 2012 of
      UTIs caused by E. coli. The mechanisms of resistance were characterized by
      phenotypic and genotypic methods and the pulsed-field gel electrophoresis (PFGE)
      was used to determine the different bacterial clusters. As expected, the highest
      incidence was observed with E. coli (60.53-73.98%) followed by K. pneumoniae
      (5.32-8.33%). ICU isolates were constantly associated with the lowest rates of
      susceptibility to extended-spectrum cephalosporins, ciprofloxacin, as well as
      most of the tested antibiotics. A 100% occurrence of CTX-M in extended-spectrum
      beta-lactamase (ESBL)-producing isolates was recorded, followed by TEM, SHV, and
      OXA. In addition, 15.9% harbored 4 different ESBL enzymes and only 13 isolates
      (14.8%) harbored only one enzyme (CTX-M). Over the years, the simultaneous
      susceptibility of E. coli to ceftazidime and ciprofloxacin decreased from 62.5%
      in 2006 to 48.7% in 2012. PFGE results demonstrated that 10 clusters were 32
      generated, denoting diversity among detected isolates. Understanding the
      epidemiology of resistance is 33 instrumental for the implementation of
      recommendations for the management of antimicrobials, infection 34 control
      measures, as well as active surveillance and antimicrobial stewardship. 

PMID- 25984514
TI  - Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal
      transitions in malignant tumors: An update.
AB  - Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial
      cell in an elongated cell with mesenchymal phenotype, which can occur in
      physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound
      healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The
      proliferation rate, metastasizing and recurrence capacity, as also the
      individualized response at chemotherapics, in both epithelial and mesenchymal
      malignant tumors is known to be influenced by reversible switch between EMT and
      mesenchymal-to-epithelial transition (MET). Although much research work has
      already been done in these fields, the specific molecular pathways of EMT,
      relating to the tumor type and tumor localization, are yet to be elucidated. In
      this paper, based on the literature and personal experience of the authors, an
      update in the field of EMT vs MET in epithelial and mesenchymal tumors is
      presented. The authors tried to present the latest data about the particularities
      of these processes, and also of the so-called endothelial-to-mesenchymal
      transition, based on tumor location. The EMT-angiogenesis link is discussed as a
      possible valuable parameter for clinical follow-up and targeted therapeutic
      oncologic management. The paper begins with presentation of the basic aspects of
      EMT, its classification and assessment possibilities, and concludes with
      prognostic and therapeutic perspectives. The particularities of EMT and MET in
      gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and
      cholangiocarcinomas, and lung, breast and prostate cancers, respectively in
      sarcomas and gastrointestinal stromal tumors are presented in detail. 

PMID- 25984515
TI  - Management of distal humeral coronal shear fractures.
AB  - Coronal shear fractures of the distal humerus are rare, complex fractures that
      can be technically challenging to manage. They usually result from a low-energy
      fall and direct compression of the distal humerus by the radial head in a hyper
      extended or semi-flexed elbow or from spontaneous reduction of a posterolateral
      subluxation or dislocation. Due to the small number of soft tissue attachments at
      this site, almost all of these fractures are displaced. The incidence of distal
      humeral coronal shear fractures is higher among women because of the higher rate
      of osteoporosis in women and the difference in carrying angle between men and
      women. Distal humeral coronal shear fractures may occur in isolation, may be part
      of a complex elbow injury, or may be associated with injuries proximal or distal
      to the elbow. An associated lateral collateral ligament injury is seen in up to
      40% and an associated radial head fracture is seen in up to 30% of these
      fractures. Given the complex nature of distal humeral coronal shear fractures,
      there is preference for operative management. Operative fixation leads to stable
      anatomic reduction, restores articular congruity, and allows initiation of early
      range-of-motion movements in the majority of cases. Several surgical exposure and
      fixation techniques are available to reconstruct the articular surface following
      distal humeral coronal shear fractures. The lateral extensile approach and
      fixation with countersunk headless compression screws placed in an anterior-to
      posterior fashion are commonly used. We have found a two-incision approach
      (direct anterior and lateral) that results in less soft tissue dissection and
      better outcomes than the lateral extensile approach in our experience. Stiffness,
      pain, articular incongruity, arthritis, and ulnohumeral instability may result if
      reduction is non-anatomic or if fixation fails. 

PMID- 25984516
TI  - Cardiovascular risk factors for acute stroke: Risk profiles in the different
      subtypes of ischemic stroke.
AB  - Timely diagnosis and control of cardiovascular risk factors is a priority
      objective for adequate primary and secondary prevention of acute stroke.
      Hypertension, atrial fibrillation and diabetes mellitus are the most common risk
      factors for acute cerebrovascular events, although novel risk factors, such as
      sleep-disordered breathing, inflammatory markers or carotid intima-media
      thickness have been identified. However, the cardiovascular risk factors profile
      differs according to the different subtypes of ischemic stroke. Atrial
      fibrillation and ischemic heart disease are more frequent in patients with
      cardioembolic infarction, hypertension and diabetes in patients with lacunar
      stroke, and vascular peripheral disease, hypertension, diabetes, previous
      transient ischemic attack and chronic obstructive pulmonary disease in patients
      with atherothrombotic infarction. This review aims to present updated data on
      risk factors for acute ischemic stroke as well as to describe the usefulness of
      new and emerging vascular risk factors in stroke patients. 

PMID- 25984518
TI  - Multidetector computed tomography of temporomandibular joint: A road less
      travelled.
AB  - This article reviews the imaging anatomy of temporomandibular joint (TMJ),
      describes the technique of multi-detector computed tomography (MDCT) of the TMJ,
      and describes in detail various osseous pathologic afflictions affecting the
      joint. Traumatic injuries affecting the mandibular condyle are most common,
      followed by joint ankylosis as a sequel to arthritis. The congenital anomalies
      are less frequent, hemifacial microsomia being the most commonly encountered
      anomaly involving the TMJ. Neoplastic afflictions of TMJ are distinctly uncommon,
      osteochondroma being one of the most common lesions. MDCT enables comprehensive
      evaluation of osseous afflictions of TMJ, and is a valuable tool for surgical
      planning. Sagittal, coronal and 3D reformatted images well depict osseous TMJ
      lesions, and their relationship to adjacent structures. 

PMID- 25984517
TI  - Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and
      management.
AB  - Tick-borne encephalitis is an infection of central nervous system caused by tick
      borne encephalitis virus transmitted to humans predominantly by tick bites.
      During the last few decades the incidence of the disease has been increasing and
      poses a growing health problem in almost all endemic European and Asian
      countries. Most cases occur during the highest period of tick activity, in
      Central Europe mainly from April to November. Tick-borne encephalitis is more
      common in adults than in children. Clinical spectrum of the disease ranges from
      mild meningitis to severe meningoencephalitis with or without paralysis. Rare
      clinical manifestations are an abortive form of the disease and a chronic
      progressive form. A post-encephalitic syndrome, causing long-lasting morbidity
      that often affects the quality of life develops in up to 50% of patients after
      acute tick-borne encephalitis. Clinical course and outcome vary by subtype of
      tick-borne encephalitis virus (the disease caused by the European subtype has
      milder course and better outcome than the disease caused by Siberian and Far
      Easter subtypes), age of patients (increasing age is associated with less
      favorable outcome), and host genetic factors. Since clinical features and
      laboratory results of blood and cerebrospinal fluid are nonspecific, the
      diagnosis must be confirmed by microbiologic findings. The routine laboratory
      confirmation of the tick-borne encephalitis virus infection is based mainly on
      the detection of specific IgM and IgG antibodies in serum (and cerebrospinal
      fluid), usually by enzyme-linked immunosorbent assay. There is no specific
      antiviral treatment for tick-borne encephalitis. Vaccination can effectively
      prevent the disease and is indicated for persons living in or visiting tick-borne
      encephalitis endemic areas. 

PMID- 25984519
TI  - Intraoperative laparoscopic complications for urological cancer procedures.
AB  - AIM: To structure the rate of intraoperative complications that requires an
      intraoperative or perioperative resolution. METHODS: We perform a literature
      review of Medline database. The research was focused on intraoperative
      laparoscopic procedures inside the field of urological oncology. General rate of
      perioperative complications in laparoscopic urologic surgery is described to be
      around 12.4%. Most of the manuscripts published do not make differences between
      pure intraoperative, intraoperative with postoperative consequences and
      postoperative complications. RESULTS: We expose a narrative statement of
      complications, possible solutions and possible preventions for most frequent
      retroperitoneal and pelvic laparoscopic surgery. We expose the results with the
      following order: retroperitoneal laparoscopic surgery (radical nephrectomy,
      partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic
      laparoscopic surgery (radical prostatectomy and radical cystectomy). CONCLUSION:
      Intraoperative complications vary from different series. More scheduled reports
      should be done in order to better understand the real rates of complications.

PMID- 25984520
TI  - Pedunculated colonic lipoma prolapsing through the anus.
AB  - Colorectal lipomas are the second most common benign tumors of the colon. These
      masses are typically incidental findings with over 94% being asymptomatic.
      Symptoms-classically abdominal pain, bleeding per rectum and alterations in bowel
      habits-may arise when lipomas become larger than 2 cm in size. Colonic lipomas
      are most often noted incidentally by colonoscopy. They may also be identified by
      abdominal imaging such as computed tomography or magnetic resonance imaging. We
      report a case of a sixty-one years old male who presented to our emergency room
      with a 6.7 cm * 6.3 cm soft tissue mucosal mass protruding transanally. The
      patient was stable with a benign abdominal examination. The mass was initially
      thought to be a rectal prolapse; however, a limited digital rectal exam was able
      to identify this as distinct from the anal canal. Since the mass was irreducible,
      it was elected to be resected under anesthesia. At surgery, manipulation of the
      mass identified that the lesion was pedunculated with a long and thickened stalk.
      A laparoscopic linear cutting stapler was used to resect the mass at its stalk.
      Pathology showed a polypoid submucosal lipoma of the colon with overlying
      ulceration and necrosis. We report this case to highlight this rare but possible
      presentation of colonic lipomas; an incarcerated, trans-anal mass with features
      suggesting rectal prolapse. Trans-anal resection is simple and effective
      treatment. 

PMID- 25984521
TI  - Small bowel diverticulitis with severe anemia and abdominal pain.
AB  - The current case report is related to a male patient with diabetes, obesity [body
      mass index (BMI) 33], hypertension and recurrence of anemia associated to melena
      and deep asthenia. M.P., a 60-year-old obese individual, was referred to our
      department by the primary care unit (PCU) of our hospital for severe anemia
      (Hemoglobin 6.5 g/dL) associated to episodes of melena and abdominal pain. In the
      past 5 mo the patient referred to the local hospital 3 times for episodes of
      melena (hemoglobin levels showed anemia 9.8 g/dL) but the main
      gastroenterological exams were completely negative (colonoscopy and gastroscopy).
      The PCU of our Hospital, after stabilization of the main parameters and blood
      transfusion for the low levels of hemoglobin, referred the patient to
      gastroenterologists: the patient was subjected to both colonoscopy and
      gastroscopy that were negative. Due to the condition of acute severe hemorrhage
      the patient, during the first 3 h from the access to the PCU, was subjected to
      arteriography that did not reveal any hemorrhagic foci or vascular alterations.
      The video capsule for the study of the small bowel showed the presence of blood
      beginning from the third portion of duodenum but deep gastroscopy did not reveal
      it. The patient was then subjected to double balloon endoscopy that revealed a
      severe diverticulosis of the small bowel with blood from the diverticula. The
      entero-tomografia computerizzata confirmed the diagnosis and revealed an
      extension of the diverticula for almost the entire small bowel (no diverticula in
      the colon). The patient was subjected to wide spectrum antibiotic therapy with
      resolution of the symptoms and stabilization of hemoglobin levels. The surgeon
      suggests no indication to surgery for the wide area involved from the disease and
      potential high risk of complication due to the high BMI. At home, the patient
      started a monthly therapy with rifaximin and probiotics associated to mesalazine.
      At present, after 12 mo from the last episode of hemorrhage, the patient is in
      good clinical condition, reduced his body weight of about 7 kg and the hemoglobin
      levels appear in slow progressive increase (last measurement 13.2 g/dL). 

PMID- 25984522
TI  - Extremely unusual case of gastrointestinal trichobezoar.
AB  - Trichobezoars (hair ball) are usually located in the stomach, but may extend
      through the pylorus into the duodenum and small bowel (Rapunzel syndrome).
      Rapunzel syndrome remains uncommon; with fewer than 40 cases reported. To the
      best of our knowledge, this case may be the first well-documented case with a
      length of 75 cm. They are almost always associated with trichotillomania and
      trichophagia or other psychiatric disorders. In the literature several treatment
      options are proposed, including removal by conventional laparotomy, laparoscopy
      and endoscopy. Herein, we are reporting an interesting case of an 18-year
      mentally retarded girl with history of trichotillomania and trichophagia who
      presented to our emergency department with a history of central abdominal pain
      associated with vomiting and constipation for five days. An examination showed a
      trichobezoar requiring emergent surgical intervention, and indicating the need
      for psychiatric treatment. The trichobezoar was treated successfully by
      laparoscopy. 

PMID- 25984523
TI  - Congenital pulmonary airway malformation: A report of two cases.
AB  - Congenital pulmonary airway malformation (CPAM), previously known as congenital
      cystic adenomatoid malformation is a congenital disorder of the lung similar to
      bronchopulmonary sequestration. In CPAM, usually an entire lobe of lung is
      replaced by a non-working cystic piece of abnormal lung tissue. This abnormal
      tissue will never function as normal lung tissue. The underlying cause for CPAM
      is not known. It occurs in approximately 1 in every 30000 pregnancies. The
      association between CPAM and malignancy has been well documented. There is a
      small risk (0.7%) of malignant transformation within the cyst. So early diagnosis
      and surgical resection is important to prevent the grave complications. Herein,
      we are reporting two interesting cases of CPAM and one belonged to Type II and
      other belonged to Type III of Stocker's classification. 

PMID- 25984524
TI  - Composite pheochromocytoma masquerading as solid-pseudopapillary neoplasm of
      pancreas.
AB  - Pheochromocytoma and ganglioneuroma form rare composite tumours of the adrenal
      medulla comprising less than 3% of all sympathoadrenal tumours. We present a case
      of intraoperatively detected adrenal medullary tumour of composite
      pheochromocytoma and ganglioneuroma diagnosed on histopathology, in a
      normotensive patient. A 50-year-old male with a past history of chronic
      obstructive pulmonary disease presented with abdominal pain and significant
      weight loss since one month. Ultrasound and contrast-enhanced computed tomography
      abdomen revealed a large lobulated lesion in the distal body and tail of pancreas
      suggestive of solid and papillary neoplasm of body and tail of pancreas. Intra
      operatively, a 15 cm * 10 cm solid lesion with cystic areas was seen arising from
      the left lower pole of the adrenal gland pushing the pancreas which appeared
      unremarkable. In our case, exploratory laparotomy with tumour excision was done.
      Extensive sectioning and microscopic examination of this adrenal tumour confirmed
      a diagnosis of composite Pheochromocytoma with Ganglioneuroma on histopathology.
      Immunophenotyping with S-100 further supported the diagnosis. The goal of this
      report is to increase the awareness of this rare disease and to further identify
      its variable presentation. 

PMID- 25984526
TI  - Corrigendum to "Synergistic effects of toxic elements on heat shock proteins".

PMID- 25984525
TI  - Neurotensin branched peptide as a tumor-targeting agent for human bladder cancer.
AB  - Despite recent advances in multimodal therapy, bladder cancer still ranks ninth
      in worldwide cancer incidence. New molecules which might improve early diagnosis
      and therapeutic efficiency for tumors of such high epidemiological impact
      therefore have very high priority. In the present study, the tetrabranched
      neurotensin peptide NT4 was conjugated with functional units for cancer-cell
      imaging or therapy and was tested on bladder cancer cell lines and specimens from
      bladder cancer surgical resections, in order to evaluate its potential for
      targeted personalized therapy of bladder cancer. Fluorophore-conjugated NT4
      distinguished healthy and cancer tissues with good statistical significance (P <
      0.05). NT4 conjugated to methotrexate or gemcitabine was cytotoxic for human
      bladder cancer cell lines at micromolar concentrations. Their selectivity for
      bladder cancer tissue and capacity to carry tracers or drugs make NT4 peptides
      candidate tumor targeting agents for tracing cancer cells and for personalized
      therapy of human bladder cancer. 

PMID- 25984527
TI  - Indoor Air Quality and Respiratory Health among Malay Preschool Children in
      Selangor.
AB  - Indoor air quality (IAQ) has been the object of several studies due to its
      adverse health effects on children. Methods. A cross-sectional comparative study
      was carried out among Malay children in Balakong (2 studied preschools) and Bangi
      (2 comparative preschools), Selangor, with the aims of determining IAQ and its
      association with respiratory health. 61 and 50 children aged 5-6 years were
      selected as studied and comparative groups. A questionnaire was used to obtain an
      exposure history and respiratory symptoms. Lung function test was carried out.
      IAQ parameters obtained include indoor concentration of particulate matter (PM),
      volatile organic compounds (VOCs), carbon monoxide (CO), carbon dioxide (CO2),
      temperature, air velocity (AV), and relative humidity. Results. There was a
      significant difference between IAQ in studied and comparative preschools for all
      parameters measured (P < 0.001) except for CO2 and AV. Studied preschools had
      higher PM and CO concentration. FVC, FEV1, FVC% and FEV1% predicted values were
      significantly lower among studied group. Exposures to PM, VOCs, and CO were
      associated with wheezing. Conclusion. The finding concluded that exposures to
      poor IAQ might increase the risk of getting lung function abnormality and
      respiratory problems among study respondents. 

PMID- 25984528
TI  - Recent advances and future perspective in microbiota and probiotics.

PMID- 25984529
TI  - Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Function of Allogeneic
      Activated Vgamma9Vdelta2 T Lymphocytes In Vitro.
AB  - BACKGROUND: Human umbilical cord mesenchymal stem cells (UC-MSCs) can regulate
      the function of immune cells. However, whether and how UC-MSCs can modulate the
      function of Vgamma9Vdelta2 T cells has not been fully understood. METHODS: The
      PBMCs or Vgamma9Vdelta2 T cells were activated and expanded with pamidronate
      (PAM) and interleukin-2 (IL-2) with or without the presence UC-MSCs. The effects
      of UC-MSCs on the proliferation, cytokine expression, and cytotoxicity of
      Vgamma9Vdelta2 T cells were determined by flow cytometry. The effects of UC-MSCs
      on Fas-L, TRAIL-expressing Vgamma9Vdelta2 T cells, and Vgamma9Vdelta2 T cell
      apoptosis were determined by flow cytometry. RESULTS: UC-MSCs inhibited
      Vgamma9Vdelta2 T cell proliferation in a dose-dependent but cell-contact
      independent manner. Coculture with UC-MSCs reduced the frequency of IFNgamma+ but
      increased granzyme B+ Vgamma9Vdelta2 T cells. UC-MSCs inhibited the cytotoxicity
      of Vgamma9Vdelta2 T cells against influenza virus H1N1 infected A549 cells and
      also reduced the frequency of Fas-L+, TRAIL+ Vgamma9Vdelta2 T cells but failed to
      modulate the apoptosis of Vgamma9Vdelta2 T cells. CONCLUSIONS: These results
      indicated that UC-MSCs efficiently suppressed the proliferation and cytotoxicity
      of Vgamma9Vdelta2 T cells and modulated their cytokine production. Fas-L and
      TRAIL were involved in the regulation. Cell contact and apoptosis of
      Vgamma9Vdelta2 T cells were not necessary for the inhibition.

PMID- 25984530
TI  - A Comprehensive Systems Biological Study of Autophagy-Apoptosis Crosstalk during
      Endoplasmic Reticulum Stress.
AB  - One of the most important tasks of a living organism is to maintain its genetic
      integrity with respect to stress. Endoplasmic reticulum (ER) has a crucial role
      in sensing cellular homeostasis by controlling metabolism, proteostasis, and
      several signaling processes. ER stressors can induce autophagy-dependent
      survival; however excessive level of stress results in apoptotic cell death.
      Although many molecular components of these networks have already been
      discovered, the analysis of the dynamical features of the regulatory network of
      life-or-death decision is still lacking. Our goal was to incorporate both
      theoretical and molecular biological techniques to explore the autophagy
      apoptosis crosstalk under ER stress. Using various levels of different ER
      stressors we confirmed that the control network always generated an evidently
      detectable autophagy-dependent threshold for apoptosis activation. We explored
      the features of this threshold by introducing both autophagy activators and
      inhibitors, and transient treatment with excessive level of ER stressor was also
      performed. Our experimental data were also supported by a stochastic approach.
      Our analysis suggests that even if the switch-like characteristic of apoptosis
      activation is hardly seen on population level the double negative feedback loop
      between autophagy and apoptosis inducers introduces bistability in the control
      network. 

PMID- 25984531
TI  - Implants in urogynecology.

PMID- 25984532
TI  - Constitutive NF- kappa B Activation Underlines Major Mechanism of Drug Resistance
      in Relapsed Refractory Diffuse Large B Cell Lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is the most common subtype of B cell non
      Hodgkin's lymphoma (NHL), encompassing 30-40% of the estimated 70,000 cases of
      NHL in 2014 in the USA. Despite major improvements with immune-chemotherapy, the
      fraction of patients who still succumb to a refractory or relapsed disease
      remains high. This review addresses whether the better understanding of the
      biology of DLBCL defines new therapeutic avenues that may overcome the emerging
      resistance of this disease to traditional immune-chemotherapy, such as rituximab
      in combination with traditional chemotherapy agents. Emerging targeted therapy
      for relapsed refractory DLBCL encompasses more complex molecular abnormalities
      involving signaling pathways other than NF-kappaB as mechanism of resistance to
      immune-chemotherapy. Our review suggests that NF-kappaB pathway is an important
      crossroad where other pathways converge as phenotype of resistance that emerges
      in patients who fail frontline and salvage immune-chemotherapy. Future efforts
      should aim at targeting the role of NF-kappaB resistance in clinical trials,
      where novel agents like lenalidomide and proteasome inhibitors with established
      activity in this perspective will be an important component in combination
      therapy, along with new monoclonal antibody, BTK-inhibitors, and other novel
      therapy agents. 

PMID- 25984533
TI  - A Novel Loss-of-Sclerostin Function Mutation in a First Egyptian Family with
      Sclerosteosis.
AB  - Sclerosteosis is a rare autosomal recessive condition characterized by increased
      bone density. Mutations in SOST gene coding for sclerostin are linked to
      sclerosteosis. Two Egyptian brothers with sclerosteosis and their apparently
      normal consanguineous parents were included in this study. Clinical evaluation
      and genomic sequencing of the SOST gene were performed followed by in silico
      analysis of the resulting variation. A novel homozygous frameshift mutation in
      the SOST gene, characterized as one nucleotide cytosine insertion that led to
      premature stop codon and loss of functional sclerostin, was identified in the two
      affected brothers. Their parents were heterozygous for the same mutation. To our
      knowledge this is the first Egyptian study of sclerosteosis and SOST gene causing
      mutation. 

PMID- 25984534
TI  - Extramedullary manifestation in multiple myeloma bears high incidence of poor
      cytogenetic aberration and novel agents resistance.
AB  - Extramedullary disease (EMD) in multiple myeloma (MM) patients is an uncommon
      event and more attention was directed toward the feature of these patients.
      Cytogenetic aberration is an important characteristic of MM and is associated
      with patients' outcome. In this study, we aimed to compare the cytogenetic
      abnormality of patients with and without extramedullary manifestation, and to
      analyze the clinical outcomes of novel agents in EMD patients. We retrospectively
      investigated data from 41 MM patients. Our analyses showed del(17p13) in 31% of
      EMD versus 13% of medullary disease (P = 0.03) and amp(1q21) in 55% versus 32% (P
      = 0.019). No differences were shown in del(13q14) and t(4;14). 24/27 patients
      with EMD at diagnosis responded to the novel agents-containing regimens. However,
      when relapsed, 70% of patients did not benefit from the sequential use of novel
      agents as salvage therapy. In 14 patients who developed EMD at relapse phase,
      only 2 patients responded to novel agents therapy. Median overall survival of
      patients with extramedullary manifestations was 30 months, in comparison to 104
      months for patients without EMD (P = 0.002). Patients with extramedullary
      manifestation bore high incidence of poor cytogenetic aberration and novel agents
      resistance. 

PMID- 25984535
TI  - Clinical characteristics of autism spectrum disorder in Israel: impact of ethnic
      and social diversities.
AB  - Despite the increased global prevalence and recognition of autistic spectrum
      disorder (ASD), it is still scarcely reported in the Arab world. Though Israel
      has a higher prevalence of ASD, a previous national survey of patients diagnosed
      between 1972 and 2004, demonstrated that 98% of them were of Jewish ancestry. The
      disproportional low number of Arab children with ASD in Israel is unclear but may
      reflect lower awareness and cultural bias. In the present study we collected
      clinical and demographic characteristics of 200 children with ASD from Arab and
      Jewish sectors in Israel that were evaluated in two child development centers. We
      compared the incidence and the medical comorbidity of autism between these two
      ethnics groups. The medical and psychiatric comorbidity profile in these children
      was similar to the worldwide published studies. In the present study the
      prevalence of autism in the Arab sector in Israel was similar to that of the
      Jewish sector. The Arab patients presented with more severe autistic
      manifestations and higher incidence of mental retardation, familial members with
      autism, and consanguinity (P < 0.05), while in the Jewish sector milder forms
      (such as Asperger syndrome and PDD-NOS) were more frequent. This discrepancy
      might be explained by both genetic and cultural factors. 

PMID- 25984536
TI  - Biomarker as a research tool in linking exposure to air particles and respiratory
      health.
AB  - Some of the environmental toxicants from air pollution include particulate matter
      (PM10), fine particulate matter (PM2.5), and ultrafine particles (UFP). Both
      short- and long-term exposure could result in various degrees of respiratory
      health outcomes among exposed persons, which rely on the individuals' health
      status. METHODS: In this paper, we highlight a review of the studies that have
      used biomarkers to understand the association between air particles exposure and
      the development of respiratory problems resulting from the damage in the
      respiratory system. Data from previous epidemiological studies relevant to the
      application of biomarkers in respiratory system damage reported from exposure to
      air particles are also summarized. RESULTS: Based on these analyses, the findings
      agree with the hypothesis that biomarkers are relevant in linking harmful air
      particles concentrations to increased respiratory health effects. Biomarkers are
      used in epidemiological studies to provide an understanding of the mechanisms
      that follow airborne particles exposure in the airway. However, application of
      biomarkers in epidemiological studies of health effects caused by air particles
      in both environmental and occupational health is inchoate. CONCLUSION: Biomarkers
      unravel the complexity of the connection between exposure to air particles and
      respiratory health.

PMID- 25984537
TI  - Updates in the management of diabetic macular edema.
AB  - Diabetes mellitus is a chronic disease which has multiple effects on different
      end-organs, including the retina. In this paper, we discuss updates on diabetic
      macular edema (DME) and the management options. The underlying pathology of DME
      is the leakage of exudates from retinal microaneurysms, which trigger subsequent
      inflammatory reactions. Both clinical and imaging techniques are useful in
      diagnosing, classifying, and gauging the severity of DME. We performed a
      comprehensive literature search using the keywords "diabetes," "macula edema,"
      "epidemiology," "pathogenesis," "optical coherence tomography," "intravitreal
      injections," "systemic treatment," "hypertension," "hyperlipidemia," "anemia,"
      and "renal disease" and collated a total of 47 relevant articles published in
      English language. The main modalities of treatment currently in use comprise
      laser photocoagulation, intravitreal pharmacological and selected systemic
      pharmacological options. In addition, we mention some novel therapies that show
      promise in treating DME. We also review systemic factors associated with
      exacerbation or improvement in DME. 

PMID- 25984538
TI  - Herpes murine model as a biological assay to test dialyzable leukocyte extracts
      activity.
AB  - Human dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low
      molecular-weight peptides that are released on disruption of peripheral blood
      leukocytes from healthy donors. DLEs improve clinical responses in infections,
      allergies, cancer, and immunodeficiencies. Transferon is a human DLE that has
      been registered as a hemoderivate by Mexican health authorities and
      commercialized nationally. To develop an animal model that could be used
      routinely as a quality control assay for Transferon, we standardized and
      validated a murine model of cutaneous HSV-1 infection. Using this model, we
      evaluated the activity of 27 Transferon batches. All batches improved the
      survival of HSV-1-infected mice, wherein average survival rose from 20.9% in
      control mice to 59.6% in Transferon-treated mice. The activity of Transferon
      correlated with increased serum levels of IFN-gamma and reduced IL-6 and TNF
      alpha concentrations. Our results demonstrate that (i) this mouse model of
      cutaneous herpes can be used to examine the activity of DLEs, such as Transferon;
      (ii) the assay can be used as a routine test for batch release; (iii) Transferon
      is produced with high homogeneity between batches; (iv) Transferon does not have
      direct virucidal, cytoprotective, or antireplicative effects; and (v) the
      protective effect of Transferon in vivo correlates with changes in serum
      cytokines. 

PMID- 25984540
TI  - Comparison of prescribing indicators of academic versus non-academic specialist
      physicians in Urmia, Iran.
AB  - OBJECTIVE: As chief prescribers, physicians could have a key role in rational
      drug use. Core prescribing indicators of all physicians have been evaluated in
      the Islamic Republic of Iran for several years, but no study has assessed the
      effects of academic status of doctors on their prescribing behaviors. We aimed to
      compare prescribing indicators of two groups of academic and non-academic
      specialist physicians working in Urmia, Iran. METHODS: In this cross-sectional
      study, prescribing indicators of the total number of 37 academic and 104 non
      academic specialist physicians in six medical specialties (infectious diseases,
      psychiatry, otorhinolaryngology, gynecology, pediatrics and general surgery) were
      studied during 2012 using Rx-analyzer, a dedicated computer application. A set of
      five quality indicators was used based on the World Health Organization and
      International Network for Rational Use of Drugs recommendations. FINDINGS:
      Totally, 709,771 medications in 269,660 prescriptions were studied. For academic
      and non-academic specialist physicians, the average number of medications per
      prescription was 2.26 and 2.65, respectively. Similarly, patients' encounters
      with injectable pharmaceuticals were 17.37% and 26.76%, respectively. The
      corresponding figures for antimicrobial agents were 33.12% and 45.46%,
      respectively. The average costs of every prescription were 6.53 and 3.30 United
      States Dollar for academic and non-academic specialist physicians, respectively.
      All the above-mentioned differences were statistically significant. CONCLUSION:
      Better prescribing patterns were observed in academic specialist physicians.
      However, they prescribed medications that were more expensive, while the reason
      was not investigated in this study. Further studies may reveal the exact causes
      of these differences.

PMID- 25984539
TI  - Vitamin D deficiency contributes to the reduction and impaired function of naive
      CD45RA+ regulatory T cell in chronic heart failure.
AB  - The effect of vitamin D pertinent to cardiovascular health on the heart itself is
      considered to shift toward an anti-inflammatory response in chronic heart failure
      (CHF); however, its underlying mechanism is not completely understood. In this
      study, we demonstrated that plasma 25(OH)D level, negatively associated with NT
      ProBNP, correlated with the decreased Treg in CHF compared to the patients with
      other cardiovascular diseases and healthy and older donors. Naive Treg cell
      (CD4(+)CD45RA(+)Foxp3(lo)T) subset, rather than whole Treg cells, contributes to
      the reduction of Treg in CHF. 1,25(OH)2D treatment maintained partial expression
      of CD45RA on CD4(+)T cell after alphaCD3/CD28 monoclonal antibodies activation
      and ameliorated the impaired CD4(+)CD45RA(+)T cell function from CHF patients
      through upregulating Foxp3 expression and IL-10 secretion in vitro. Low level of
      vitamin D receptor (VDR) was detected in CD4(+)CD45RA(+)T cell of CHF than
      control, while 1,25(OH)2D treatment increased the VDR expression to exert its
      immunosuppression on T cell. The results of this study might provide tangible
      evidence to our knowledge of the impact of vitamin D supplementation on naive
      Tregs, which may offer new means of preventing and treating CHF. 

PMID- 25984541
TI  - Evaluation of productivity in Iranian pharmaceutical companies: A DEA-based
      Malmquist approach and panel data analysis.
AB  - OBJECTIVE: In this study, we aimed to assess comparative productivity of 21
      pharmaceutical companies in Iran during 2000-2013. METHODS: To evaluate the
      productivity trend of pharmaceutical companies in Iran, we used data envelopment
      analysis-based Malmquist index. "Total assets" and "capital stock" as inputs and
      "net sales" and "net profit" as outputs extracted from Tehran stock exchange,
      were selected to be included in the analysis. This method provides the
      possibility for analyzing the performance of each company in term of productivity
      changes over time. We also used an estimation generalized least square panel data
      model to identify the factors that might affect productivity of pharmaceutical
      companies in Iran using EViews 7 and Deep 2.1 software. FINDINGS: The mean total
      productivity during all years of the study was 0.9829, which indicates the
      improvement in their overall productivity. The results, over the 13-year period,
      indicated that the range of productivity changes in pharmaceutical companies,
      that were included in this study, was between 0.884 and 1.098. Panel data model
      indicated that age of company could positively (t = 4.765978, P < 0.001) and
      being located in cities other than Tehran (the capital) could negatively (t = 
      5.369549, P < 0.001) affect the productivity of pharmaceutical companies. The
      analysis showed the new policy (brand-generic scheme) and also the type of
      ownership did not have a significant effect on the productivity of pharmaceutical
      companies. CONCLUSION: In this study, pharmaceutical productivity trends were
      fluctuated that could be due to the sub-optimal attention of policy makers and
      managers of pharmaceutical companies toward long-term strategic planning,
      focusing on productivity improvement.

PMID- 25984542
TI  - The comparative study of intravenous Ondansetron and sub-hypnotic Propofol dose
      in control and treatment of intrathecal Sufentanil-induced pruritus in elective
      caesarean surgery.
AB  - OBJECTIVE: Pruritus is a common and disturbing side effect of neuraxial opioids
      after cesarean section. The purpose of this study was to compare the efficacy of
      intravenous ondansetron and sub-hypnotic dose of propofol in control and
      treatment of intrathecal sufentanil induced pruritus in cesarean surgery.
      METHODS: Totally, 90 parturient with American Society of Anesthesiology physical
      status grade I-II, undergoing spinal anesthesia with 2.5 MUg sufentanil and 10 mg
      bupivacaine 0.5% were enrolled to this randomized, prospective, double-blind
      study. The women were randomly assigned to two groups who received 8 mg
      ondansetron or 10 mg propofol to treat pruritus grade >=3. The patient was
      evaluated after 5 min and in the lack of successful treatment, the doses of two
      drugs repeated and if the pruritus is on-going, the exact treatment with naloxone
      was done. FINDINGS: The incidence of pruritus was 69.3%. Both groups were well
      matched. The peak time pruritus was 30-75 min after injection. The percentage of
      individuals consumed naloxone were 6.8% and 15.9% in ondansetron and propofol
      groups, respectively (P = 0.18). The mean score of satisfaction (according to
      visual analog scale criteria) was 9.09 +/- 1.1 in ondansetron group and 9.3 +/-
      1.07 in the propofol group (P = 0.39). CONCLUSION: Ondansetrone and sub-hypnotic
      dose of propofol are both safe and well-tolerated. Due to their same efficacy in
      the treatment of intrathecal sufentanil-induced pruritus, they can be widely used
      in clinical practice.

PMID- 25984543
TI  - Identification of possible adverse drug reactions in clinical notes: The case of
      glucose-lowering medicines.
AB  - OBJECTIVE: Through manual review of clinical notes for patients with type 2
      diabetes mellitus attending a Danish diabetes center, the aim of the study was to
      identify adverse drug reactions (ADRs) associated with three classes of glucose
      lowering medicines: "Combinations of oral blood-glucose lowering medicines"
      (A10BD), "dipeptidyl peptidase-4 (DDP-4) inhibitors" (A10BH), and "other blood
      glucose lowering medicines" (A10BX). Specifically, we aimed to describe the
      potential of clinical notes to identify new ADRs and to evaluate if sufficient
      information can be obtained for causality assessment. METHODS: For observed
      adverse events (AEs) we extracted time to onset, outcome, and suspected
      medicine(s). AEs were assessed according to World Health Organization-Uppsala
      Monitoring Centre causality criteria and analyzed with respect to suspected
      medicines, type of ADR (system organ class), seriousness and labeling status.
      FINDINGS: A total of 207 patients were included in the study leading to the
      identification of 163 AEs. 14% were categorized as certain, 60% as
      probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two
      were serious: peripheral edema associated with sitagliptin and stomach ulcer
      associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with
      "other blood glucose lowering medications," the remaining 2 (13%) with "DDP-4
      inhibitors." CONCLUSION: Clinical notes could potentially reveal unlabeled ADRs
      associated with prescribed medicines and sufficient information is generally
      available for causality assessment. However, manual review of clinical notes is
      too time-consuming for routine use and hence there is a need for developing
      information technology (IT) tools for automatic screening of patient records with
      the purpose to detect information about potentially serious and unlabeled ADRs.

PMID- 25984544
TI  - Usefulness of Danaparoid sodium in patients with Heparin-induced thrombocytopenia
      after cardiac surgery.
AB  - OBJECTIVE: Thrombocytopenia is a common problem in cardiovascular surgery
      patients. However, heparin-induced thrombocytopenia (HIT) is a rare but life
      threatening complication of prophylaxis or treatment with heparin. Prompt
      management of HIT with an alternative anticoagulant is necessary due to the
      extreme risk of thrombotic complications. Therefore, we evaluated the effects of
      danaparoid in the treatment of HIT in patients with cardiac surgery who are at
      moderate to high risk of HIT. METHODS: A prospective observational study
      involving 418 postcardiac surgery patients who received unfractionated heparin
      and low-molecular weight heparin was conducted in an educational tertiary cardiac
      care hospital in Iran. All patients were assessed for HIT type II based on
      thrombocytopenia and pretest clinical scoring system, the "4T's" score. HIT
      patients were treated with 1500-2500 units intravenous bolus danaparoid sodium
      followed by 200-400 units/h for a mean of 5 days. Successful response to
      danaparoid therapy, defined as augmentation in platelet count and improvement of
      thrombotic events was assessed in all patients treated with danaparoid. FINDINGS:
      According to pretest clinical score (4T's), the probability of HIT was high in 14
      (3.3%) patients and intermediate in three ones (0.7%). 15 patients with HIT were
      treated with danaparoid. One death occurred in danaparoid-treated group due to
      persistent thrombocytopenia. The rest of patients were treated successfully with
      danaparoid without any major thrombotic complication. CONCLUSION: According to
      our data and the previous studies', HIT can be managed prosperously with
      danaparoid in postcardiac surgery patients. However, with the absence of any
      increase in platelet count after 3-5 days of danaparoid therapy and/or the
      occurrence of a new thrombotic event, danaparoid cross-reactivity with heparin
      should be suspected.

PMID- 25984545
TI  - Different doses of intravenous Magnesium sulfate on cardiovascular changes
      following the laryngoscopy and tracheal intubation: A double-blind randomized
      controlled trial.
AB  - OBJECTIVE: Laryngoscopy and intratracheal intubation may cause acute hemodynamic
      instabilities due to catecholamine release. Magnesium sulfate (MgSO4) prevents
      catecholamine release and results in bradycardia and vasodilatation, so can be
      used to diminish complications of laryngoscopy and intubation in doses > 50
      mg/kg. The aim of this study was to compare the different doses of MgSO4 used to
      improve cardiovascular instabilities due to laryngoscopy and intratracheal
      intubation. METHODS: In this double-blind randomized controlled trial, 120
      patients undergoing elective surgery were divided equally into four groups (n =
      30) and received different doses of MgSO4 as case groups (Group I: 30 mg/kg,
      Group II: 40 mg/kg, Group III: 50 mg/kg) or the equal volume of normal saline as
      a control group. The patients' hemodynamic status was recorded at baseline,
      before laryngoscopy and in 1, 3, 5, and 10 minutes after laryngoscopy.
      Bradycardia, tachycardia, hypertension, hypotension, ST-T changes, arrhythmias,
      and duration of extubation and laryngoscopy were also recorded. FINDINGS: There
      was no significant difference in heart rate between four groups (Pbaseline =
      0.46, Ppreoperation = 0.55, P1 min = 0.86, P3 min = 0.30, P5 min = 0.63, P10 min
      = 0.74). Systolic, diastolic and mean arterial pressures were statistically
      significant less at 1, 3, and 5 minutes after intubation in comparison with other
      times of following-up in the three groups received MgSO4 than the control group.
      CONCLUSION: The use of MgSO4 in doses less than 50 mg/kg can be effective to
      reduce cardiovascular instability related to laryngoscopy and tracheal
      intubation.

PMID- 25984546
TI  - Polypharmacy in the elderly.
AB  - OBJECTIVE: The objective was to assess the frequency of polypharmacy and
      potential complications among local seniors. METHODS: A cross-sectional
      convenience sample of 59 adults aged above 65 years was interviewed at Cuyahoga
      county (U.S. state of Ohio) senior programs. Polypharmacy was defined as more
      than five prescribed medications. Primary outcomes were frequent missed doses,
      one or more duplicate drug/s, and equal or more than one contraindicated drug
      combinations. FINDINGS: Among seniors with the mean age of 76.9 years (25.4%
      male), 40.6% used multiple pharmacies and 35.6% had polypharmacy. Of all seniors
      with polypharmacy, about 57% had contraindicated drug combinations. Polypharmacy
      was associated with duplication (P = 0.02), but not frequent missed doses (P =
      0.20). CONCLUSION: As shown by this study, polypharmacy was associated with
      duplicated therapy and contraindicated drug combinations. Improved communications
      among seniors, physicians, and pharmacists is necessary to minimize adverse
      consequences of polypharmacy.

PMID- 25984547
TI  - Midazolam premedication for Ketamine-induced emergence phenomenon: A prospective
      observational study.
AB  - OBJECTIVE: Ketamine administration is known to induce hemodynamic pressor
      response and psychomimetic effects which could be attenuated by appropriate
      premedication. The present study was designed to evaluate the effect of midazolam
      on hemodynamic stability and postoperative emergence phenomenon following
      ketamine anesthesia. METHODS: This was a prospective observational study
      including 30 adult patients with American Society of Anesthesiologists physical
      grades I and II scheduled for elective short surgeries under ketamine anesthesia.
      Patients were premedicated with midazolam (0.02 mg/kg intravenously) before the
      ketamine induction (1 mg/kg intravenously). Demographic data and hemodynamic
      variables were observed during the perioperative period. Pain score by visual
      analog scale score and psychomimetic effects were recorded postoperatively.
      FINDINGS: The mean +/- standard deviation of heart rate, systolic blood pressure,
      diastolic blood pressure, and respiratory rate were decreased postoperatively
      (85.3 +/- 11.4, 120.7 +/- 8.2, 79.2 +/- 5.5, 13.5 +/- 1.8, respectively) compared
      to intraoperative period (88.53 +/- 14.1, 123.83 +/- 13.8, 83 +/- 9.1, 14.13 +/-
      2.0, respectively). There was statistically significant decrease in systolic (P =
      0.03) and diastolic (P = 0.002) blood pressure, but not with heart rate and
      respiratory rate. Eighty percent of patients had no pain at 1/2 hour and 1 hour,
      while this increased to 90% at 2 hours postoperatively. Mild emergence delirium
      was noted in 13.3% and 16.7% at 1/2 hour and 1 hour, respectively, which
      decreased to 13.3% at 2 hours. Dreams were noticed in 20%, 27% and 10% of
      patients at 1/2 hour, 1 and 2 hours after surgery, respectively. CONCLUSION:
      Midazolam premedication in ketamine anesthesia effectively attenuated the
      hemodynamic pressor response and postoperative emergence phenomenon. Hence, the
      combination of midazolam with ketamine can be safely used for short surgical
      painful procedures in adults.

PMID- 25984548
TI  - Knowledge, awareness, and perception of contraception among senior pharmacy
      students in Malaysia: A pilot study.
AB  - OBJECTIVE: This study aimed to assess the knowledge, awareness, and perception of
      contraception among senior pharmacy students of a public sector university in
      Malaysia. METHODS: A cross-sectional, questionnaire-based study was conducted
      among senior pharmacy students. The pretested questionnaire was used to collect
      data from the participants over the period of 1-month. The questionnaire was
      divided into four sections, for gathering the information about students'
      demographic data, and their knowledge, attitudes, and perception toward
      contraception. Data were statistically analyzed using SPSS version 20. FINDINGS:
      The response rate was 68.6%. The results showed that the contraceptive knowledge
      was comparatively higher in year four students (P < 0.001), married respondents
      (P < 0.001) and those taking elective courses (P = 0.022) as compared to their
      respective counterparts. Majority of the students were well aware and had a
      positive perception about contraception. CONCLUSION: Overall findings reflect
      that the majority of the students had good knowledge, perception, and awareness
      about contraception. The study recommends future studies to be conducted covering
      different pharmacy schools across the country to further establish the results.

PMID- 25984549
TI  - Multiple cutaneous necrotic lesions associated with Interferon beta-1b injection
      for multiple sclerosis treatment: A case report and literature review.
AB  - Multiple sclerosis (MS) is a chronic and debilitating inflammatory autoimmune
      disorder of the central nervous system. MS patients may experience severe local
      inflammatory skin reactions during disease-modifying therapy with subcutaneously
      injected interferon-beta-1b (IFN-beta). We report the case of a 49-year-old woman
      with relapsing-remitting MS, who developed multiple cutaneous necrotic ulcers on
      both arms and thighs after 3 months of treatment with subcutaneous IFN-beta-1b.
      The biopsy specimens showed skin and subcutaneous tissue necrosis. We diagnosed
      the skin lesions as cutaneous necrotic ulcerations associated with IFN-beta-1b
      injection. The treatment included ending the use of subcutaneously injected IFN
      beta-1b and switching to intramuscularly injected IFN-beta-1a because of the
      multiple cutaneous necrotic ulcers. The injection of IFN-beta-1b in the areas
      with lesions was stopped, and the patient's clinical condition improved with the
      addition of routine wound care, surgical debridement, and skin grafting. This
      report is intended to raise awareness about severe adverse skin reactions which
      may rarely occur with subcutaneous IFN-beta-1b injection. Early recognition and
      correction of the injection technique and switching to other forms of interferon
      can help to prevent these complications. 

PMID- 25984550
TI  - Contextual learning of L2 word meanings: Second language proficiency modulates
      behavioural and ERP indicators of learning.
AB  - New word learning occurs incidentally through exposure to language. Hypothesizing
      that effectiveness of contextual word learning in a second language (L2) depends
      on the quality of existing lexical semantic knowledge, we tested more and less
      proficient adult bilinguals in an incidental word learning task. One day after
      being exposed to rare words in an L2 (English) reading task, the bilinguals read
      sentences with the newly-learned words in the sentence-final position, followed
      by related or unrelated meaning probes. Both proficiency groups showed some
      learning through faster responses on related trials and a frontal N400 effect
      observed during probe word reading. However, word learning was more robust for
      the higher-proficiency group, who showed a larger semantic relatedness effect in
      unfamiliar contexts and a canonical N400 (central-parietal). The results suggest
      that the ability to learn the meanings of new words from context depends on the
      L2 lexical semantic knowledge of the reader.

PMID- 25984551
TI  - Without his shirt off he saved the child from almost drowning: interpreting an
      uncertain input.
AB  - Unedited speech and writing often contains errors, e.g., the blending of
      alternative ways of expressing a message. As a result comprehenders are faced
      with decisions about what the speaker may have intended, which may not be the
      same as the grammatically-licensed compositional interpretation of what was said.
      Two experiments investigated the comprehension of inputs that may have resulted
      from blending two syntactic forms. The results of the experiments suggest that
      readers and listeners tend to repair such utterances, restoring them to the
      presumed intended structure, and they assign the interpretation of the corrected
      utterance. Utterances that are repaired are expected to also be acceptable when
      they are easy to diagnose/repair and they are "familiar", i.e., they correspond
      to natural speech errors. The results of the experiments established a continuum
      ranging from outright linguistic illusions with no indication that listeners and
      readers detected the error (the inclusion of almost in A passerby rescued a child
      from almost being run over by a bus.), to a majority of unblended interpretations
      for doubled quantifier sentences (Many students often turn in their assignments
      late) to only a third undoubled implicit negation (I just like the way the
      president looks without his shirt off.) The repair or speech error reversal
      account offered here is contrasted with the noisy channel approach (Gibson et
      al., 2013) and the good enough processing approach (Ferreiera et al., 2002).

PMID- 25984552
TI  - Acidosis Sensing Receptor GPR65 Correlates with Anti-Apoptotic Bcl-2 Family
      Member Expression in CLL Cells: Potential Implications for the CLL
      Microenvironment.
AB  - The tumor microenvironment is generally an acidic environment, yet the effect of
      extracellular acidosis on chronic lymphocytic leukemia (CLL) is not well
      established. Here we are the first to report that the extracellular acid sensing
      G-protein coupled receptor, GPR65, is expressed in primary CLL cells where its
      level correlate strongly with anti-apoptotic Bcl-2 family member levels. GPR65
      expression is found normally within the lymphoid lineage and has not been
      previously reported in CLL. We demonstrate a wide range of GPR65 mRNA expression
      among CLL 87 patient samples. The correlation between GPR65 mRNA levels and Bcl-2
      mRNA levels is particularly strong (r=0.8063, p= <0.001). The correlation extends
      to other anti-apoptotic Bcl-2 family members, Mcl-1 (r=0.4847, p=0.0010) and Bcl
      xl (r=0.3411, p=0.0252), although at lower levels of significance. No correlation
      is detected between GPR65 and levels of the pro-apoptotic proteins BIM, PUMA or
      NOXA. GPR65 expression also correlates with the favorable prognostic marker of
      13q deletion. The present findings suggest the acid sensing receptor GPR65 may be
      of significance to allow CLL tolerance of extracellular acidosis. The correlation
      of GPR65 with Bcl-2 suggests a novel cytoprotective mechanism that enables CLL
      cell adaptation to acidic extracellular conditions. These findings suggest the
      potential value of targeting GPR65 therapeutically.

PMID- 25984553
TI  - Intention Tremor of the Legs in Essential Tremor: Prevalence and Clinical
      Correlates.
AB  - OBJECTIVE: To estimate the prevalence and assess the clinical correlates of
      intention tremor in the legs in essential tremor (ET) patients. BACKGROUND: The
      cerebellar features of ET are of growing interest to clinical neurologists. Arm
      tremor has an intentional component in many ET patients. Intention tremor in the
      legs, however, has never been systematically evaluated. METHODS: One-hundred
      twenty-eight ET patients were enrolled in a clinical-epidemiological study at
      Columbia University. A videotaped neurological examination included 10 toe-to
      target movements with each foot. Videotapes were independently reviewed by two
      movement disorder neurologists who noted the presence vs. absence of intentional
      leg tremor. Two patients underwent quantitative computerized tremor analysis to
      study the physiological characteristics of the tremor. RESULTS: Thirty-five
      patients (27.3%) had intentional leg tremor; in 21, tremor was unilateral and in
      14 it was bilateral. The 35 patients with intentional leg tremor did not differ
      from the remaining 93 patients in their clinical characteristics. Analyses
      comparing the 14 patients with bilateral intentional leg tremor to the 93
      patients with no intentional leg tremor showed trends towards longer disease
      duration and more severe intentional arm tremor in the former. Tremor analysis
      showed a 3-fold increase in average tremor amplitude from movement onset to the
      point just prior to touching the target. CONCLUSIONS: Our data suggest that
      intentional leg tremor, another cerebellar feature, is common in ET patients. The
      tremor may be associated with longer disease duration and more severe intentional
      arm tremor, but these preliminary trends need to be assessed in larger study
      samples.

PMID- 25984554
TI  - Multivariate fMRI Analysis using Optimally-Discriminative Voxel-Based Analysis.
AB  - This significantly extends Multi-Voxel Pattern Analysis (MVPA) methods, such as
      the Searchlight and related methods, by building on an approach that was recently
      proposed for structural brain images, and was named Optimally-Discriminative
      Voxel-Based Analysis (ODVBA), which uses machine learning models to determine the
      optimal anisotropic filtering of images that enhances group differences. Precise
      spatial maps of activation are computed by tallying the weights of each voxel to
      all of the neighborhood in which it belongs, and significance maps are obtained
      via permutation testing. We adapt this idea to both single and multi-subject fMRI
      analysis. Both simulated data and real data from 12 adolescent subjects who
      completed a standard working memory task demonstrated the use of ODVBA in fMRI
      improves accuracy and spatial specificity of activation detection over
      Searchlight.

PMID- 25984555
TI  - Ultrasonic-heating-encoded photoacoustic tomography with virtually augmented
      detection view.
AB  - Photoacoustic (PA) imaging of arbitrarily-shaped or oriented objects may miss
      important features because PA waves propagate normal to structure boundaries and
      may miss the acoustic detectors when the detection view has a limited angular
      range. To overcome this long-standing problem, we present an ultrasonic thermal
      encoding approach that is universally applicable. We exploit the temperature
      dependence of the Grueneisen parameter and encode a confined [[What does confined
      mean here?]] voxel using heat generated by a focused ultrasonic transducer. The
      PA amplitude from the encoded voxel is increased while those from the neighboring
      voxels are unchanged. Consequently, the amplitude-increased PA waves propagate in
      all directions due to the round cross-section of the encoded region and thus can
      be received at any viewing angle on the cross-sectional plane [[Please check
      throughout the manuscript for similar places.]]. We built a mathematical model
      for the thermally encoded PA tomography, performed a numerical simulation, and
      experimentally validated the ultrasonic thermal encoding efficiency. As a proof
      of concept, we demonstrate full-view in vivo vascular imaging and compare it to
      the original linear-array PA tomography system, showing dramatically enhanced
      imaging of arbitrarily oriented blood vessels. Since ultrasonic heating can be
      focused deeply, this method can be applied to deep tissue imaging and is
      promising for full-view imaging of other features of biomedical interest, such as
      tumor margins.

PMID- 25984556
TI  - Insulin-like growth factor (IGF) signaling in tumorigenesis and the development
      of cancer drug resistance.
AB  - One of the greatest obstacles to current cancer treatment efforts is the
      development of drug resistance by tumors. Despite recent advances in diagnostic
      practices and surgical interventions, many neoplasms demonstrate poor response to
      adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis
      for many patients afflicted with these aggressive cancers remains bleak. The
      insulin-like growth factor (IGF) signaling axis has been shown to play critical
      role in the development and progression of various tumors. Many basic science and
      translational studies have shown that IGF pathway modulators can have promising
      effects when used to treat various malignancies. There also exists a substantial
      body of recent evidence implicating IGF signaling dysregulation in the dwindling
      response of tumors to current standard-of-care therapy. By better understanding
      both the IGF-dependent and -independent mechanisms by which pathway members can
      influence drug sensitivity, we can eventually aim to use modulators of IGF
      signaling to augment the effects of current therapy. This review summarizes and
      synthesizes numerous recent investigations looking at the role of the IGF pathway
      in drug resistance. We offer a brief overview of IGF signaling and its general
      role in neoplasia, and then delve into detail about the many types of human
      cancer that have been shown to have IGF pathway involvement in resistance and/or
      sensitization to therapy. Ultimately, our hope is that such a compilation of
      evidence will compel investigators to carry out much needed studies looking at
      combination treatment with IGF signaling modulators to overcome current therapy
      resistance.

PMID- 25984558
TI  - Genomic Analysis of the Evolution and Global Spread of Hyper-invasive
      Meningococcal Lineage 5.
AB  - BACKGROUND: The predominant model for bacterial pandemics is the emergence of a
      virulent variant that diversifies as it spreads in human populations. We
      investigated a 40-year meningococcal disease pandemic caused by the hyper
      invasive ET-5/ST-32 complex. METHODS: A global collection of Neisseria
      meningitidis isolates dating from 1969 to 2008 was whole genome sequenced (WGS)
      and analysed using a gene-by-gene approach at http://pubmlst.org/neisseria.
      FINDINGS: Analysis of WGS data identified a 'Lineage 5 pan genome' of 1940 genes,
      1752 (92%) of which were present in all isolates (Lineage 5 'core genome').
      Genetic diversity, which was mostly generated by horizontal gene transfer, was
      unevenly distributed in the genome; however, genealogical analysis of diverse and
      conserved core genes, accessory genes, and antigen encoding genes, robustly
      identified a star phylogeny with a number of sub-lineages. Most European and
      American isolates belonged to one of two closely related sub-lineages, which had
      diversified before the identification of the pandemic in the 1970s. A third,
      genetically more diverse sub-lineage, was associated with Asian isolates. Several
      isolates had acquired DNA from the related gonococcus. INTERPRETATION: These data
      were inconsistent with a single point of origin followed by pandemic spread,
      rather suggesting that the sub-lineages had diversified and spread by
      asymptomatic transmission, with multiple distinct strains causing localised
      hyperendemic outbreaks.

PMID- 25984557
TI  - MicroRNAs: Role in Hepatitis C Virus pathogenesis.
AB  - Hepatitis C virus (HCV) is a global health burden with an estimated 170-200
      million peoples chronically infected worldwide. HCV infection remains as an
      independent risk factor for chronic hepatitis, liver cirrhosis, hepatocellular
      carcinoma, and a major reason for liver transplantation. Discovery of direct
      acting antiviral (DAA) drugs have shown promising results with more than 90%
      success rate in clearing the HCV RNA in patients, although long-term consequences
      remain to be evaluated. microRNAs (miRNAs) are important players in establishment
      of HCV infection and target crucial host cellular factors needed for productive
      HCV replication and augmented cell growth. Altered expression of miRNAs is
      involved in the pathogenesis associated with HCV infection by controlling
      signaling pathways such as immune response, proliferation and apoptosis. miRNA is
      emerging as a means of communication between various cell types inside the liver.
      There is likely possibility of developing circulating miRNAs as biomarkers of
      disease progression and can also serve as diagnostic tool with potential of early
      therapeutic intervention in HCV associated end stage liver disease. This review
      focuses on recent studies highlighting the contribution of miRNAs in HCV life
      cycle and their coordinated regulation in HCV mediated liver disease progression.

PMID- 25984559
TI  - Comparing the Coronal Seal of Different Thicknesses of MTA with Gutta-Percha
      after Post Space Preparation.
AB  - INTRODUCTION: The aim of this study was to compare the coronal seal of different
      thicknesses of MTA with gutta-percha after post space preparation. MATERIALS AND
      METHODS: A total of 50 maxillary central incisors randomly divided into 5
      experimental groups (n = 8). After preparation of the root canals with step back
      technique, in groups 1 and 2, post spaces were prepared and 4 or 5 mm gutta
      percha remained in the apical, respectively. In groups 3, 4, and 5, there was 1-2
      and 3 mm MTA in the apical, respectively. The ten teeth serve as control groups.
      The teeth were connected to a bacterial microleakage evaluation system. The study
      period was 120 days and the samples were evaluated on ten-day intervals; Meier
      Kaplan technique was used for estimation of the mean time of microleakage to
      occur. Log-rank test was used for comparison of microleakage. RESULTS: Number of
      samples exhibiting microleakage in MTA was less than those of gutta-percha at all
      intervals. Means of days with no microleakage were maximum and minimum with 3 mm
      MTA and 4 mm gutta-percha, respectively. CONCLUSION: Obturation of root canals
      using the MTA technique provides a proper seal with the minimum thickness of MTA
      in teeth requiring post space preparation.

PMID- 25984560
TI  - A novel way to relate ontology classes.
AB  - The existing ontologies in the semantic web typically have anonymous union and
      intersection classes. The anonymous classes are limited in scope and may not be
      part of the whole inference process. The tools, namely, the pellet, the jena, and
      the protege, interpret collection classes as (a) equivalent/subclasses of union
      class and (b) superclasses of intersection class. As a result, there is a
      possibility that the tools will produce error prone inference results for
      relations, namely, sub-, union, intersection, equivalent relations, and those
      dependent on these relations, namely, complement. To verify whether a class is
      complement of other involves utilization of sub- and equivalent relations.
      Motivated by the same, we (i) refine the test data set of the conference ontology
      by adding named, union, and intersection classes and (ii) propose a match
      algorithm to (a) calculate corrected subclasses list, (b) correctly relate
      intersection and union classes with their collection classes, and (c) match
      union, intersection, sub-, complement, and equivalent classes in a proper
      sequence, to avoid error prone match results. We compare the results of our
      algorithms with those of a candidate reasoner, namely, the pellet reasoner. To
      the best of our knowledge, ours is a unique attempt in establishing a novel way
      to relate ontology classes. 

PMID- 25984562
TI  - Theory of partial agonist activity of steroid hormones.
AB  - The different amounts of residual partial agonist activity (PAA) of antisteroids
      under assorted conditions have long been useful in clinical applications but
      remain largely unexplained. Not only does a given antagonist often afford unequal
      induction for multiple genes in the same cell but also the activity of the same
      antisteroid with the same gene changes with variations in concentration of
      numerous cofactors. Using glucocorticoid receptors as a model system, we have
      recently succeeded in constructing from first principles a theory that accurately
      describes how cofactors can modulate the ability of agonist steroids to regulate
      both gene induction and gene repression. We now extend this framework to the
      actions of antisteroids in gene induction. The theory shows why changes in PAA
      cannot be explained simply by differences in ligand affinity for receptor and
      requires action at a second step or site in the overall sequence of reactions.
      The theory also provides a method for locating the position of this second site,
      relative to a concentration limited step (CLS), which is a previously identified
      step in glucocorticoid-regulated transactivation that always occurs at the same
      position in the overall sequence of events of gene induction. Finally, the theory
      predicts that classes of antagonist ligands may be grouped on the basis of their
      maximal PAA with excess added cofactor and that the members of each class differ
      by how they act at the same step in the overall gene induction process. Thus,
      this theory now makes it possible to predict how different cofactors modulate
      antisteroid PAA, which should be invaluable in developing more selective
      antagonists.

PMID- 25984563
TI  - Craving Ravens: Individual 'haa' Call Rates at Feeding Sites as Cues to
      Personality and Levels of Fission-Fusion Dynamics?
AB  - Common ravens aggregate in large non-breeder flocks for roosting and foraging
      until they achieve the status of territorial breeders. When discovering food,
      they produce far-reaching yells or 'haa' calls, which attract conspecifics. Due
      to the high levels of fission-fusion dynamics in non-breeders' flocks, assemblies
      of feeding ravens were long thought to represent anonymous aggregations. Yet, non
      breeders vary in their degree of vagrancy, and 'haa' calls convey individually
      distinct acoustic features, which are perceived by conspecifics. These findings
      give rise to the assumption that raven societies are based on differential social
      relationships on an individual level. We investigated the occurrence of 'haa'
      calling and individual call rates in a group of individually marked free-ranging
      ravens. Calling mainly occurred in subadult and adult females, which showed low
      levels of vagrancy. Call rates differed significantly between individuals and
      with residency status, and were correlated with calling frequency and landing
      frequency. Local ravens called more often and at higher rates, and were less
      likely to land at the feeding site than vagrant birds. The results are discussed
      with respect to individual degrees of vagrancy, which may have an impact on
      social knowledge and communication in this species.

PMID- 25984561
TI  - Vascular Aging across the Menopause Transition in Healthy Women.
AB  - Vascular aging, featuring endothelial dysfunction and large artery stiffening, is
      a major risk factor for developing cardiovascular disease (CVD). In women,
      vascular aging appears to be accelerated during the menopause transition,
      particularly around the late perimenopausal period, presumably related to
      declines in ovarian function and estrogen levels. The mechanisms underlying
      endothelial dysfunction and large artery stiffening with the menopause transition
      are not completely understood. Oxidative stress and the proinflammatory cytokine
      tumor necrosis factor-alpha contribute to endothelial dysfunction and large
      artery stiffening in estrogen-deficient postmenopausal women. Habitual endurance
      exercise attenuates the age-related increase in large artery stiffness in
      estrogen-deficient postmenopausal women and can reverse arterial stiffening to
      premenopausal levels in estrogen-replete postmenopausal women. In contrast,
      estrogen status appears to play a key permissive role in the adaptive response of
      the endothelium to habitual endurance exercise in that endothelial improvements
      are absent in estrogen-deficient women but present in estrogen-replete women. We
      review here the current state of knowledge on the biological defects underlying
      vascular aging across the menopause transition, with particular focus on
      potential mechanisms, the role of habitual exercise in preserving vascular
      health, and key areas for future research.

PMID- 25984564
TI  - Unrewarded Object Combinations in Captive Parrots.
AB  - In primates, complex object combinations during play are often regarded as
      precursors of functional behavior. Here we investigate combinatory behaviors
      during unrewarded object manipulation in seven parrot species, including kea,
      African grey parrots and Goffin cockatoos, three species previously used as model
      species for technical problem solving. We further examine a habitually tool using
      species, the black palm cockatoo. Moreover, we incorporate three neotropical
      species, the yellow- and the black-billed Amazon and the burrowing parakeet.
      Paralleling previous studies on primates and corvids, free object-object
      combinations and complex object-substrate combinations such as inserting objects
      into tubes/holes or stacking rings onto poles prevailed in the species previously
      linked to advanced physical cognition and tool use. In addition, free object
      object combinations were intrinsically structured in Goffin cockatoos and in kea.

PMID- 25984565
TI  - Chemical and Structural Aspects of Ebola Virus Entry Inhibitors.
AB  - The Ebolaviruses are members of the family Filoviridae ("filoviruses") and cause
      severe hemhorragic fever with human case fatality rates as high as 90%. Infection
      requires attachment of the viral particle to cells and triggering of membrane
      fusion between the host and viral membranes, a process that occurs in the host
      endosome and is facilitated by the envelope glycoprotein (GP). One potential
      strategy for therapeutic intervention is the development of agents (antibodies,
      peptides, and small molecules) that can interfere with viral entry aspects such
      as attachment, uptake, priming, or membrane fusion. This paper highlights recent
      developments in the discovery and evaluation of therapeutic entry inhibitors and
      identifies opportunities moving forward. 

PMID- 25984566
TI  - Putting Tuberculosis (TB) To Rest: Transformation of the Sleep Aid, Ambien, and
      "Anagrams" Generated Potent Antituberculosis Agents.
AB  - Zolpidem (Ambien, 1) is an imidazo[1,2-a]pyridine-3-acetamide and an approved
      drug for the treatment of insomnia. As medicinal chemists enamored by how
      structure imparts biological function, we found it to have strikingly similar
      structure to the antitubercular imidazo[1,2-a]pyridine-3-carboxyamides. Zolpidem
      was found to have antituberculosis activity (MIC of 10-50 MUM) when screened
      against replicating Mycobacterium tuberculosis (Mtb) H37Rv. Manipulation of the
      Zolpidem structure, notably, to structural isomers ("anagrams"), attains
      remarkably improved potency (5, MIC of 0.004 MUM) and impressive potency against
      clinically relevant drug-sensitive, multi- and extensively drug-resistant Mtb
      strains (MIC < 0.03 MUM). Zolpidem anagrams and analogues were synthesized and
      evaluated for their antitubercular potency, toxicity, and spectrum of activity
      against nontubercular mycobacteria and Gram-positive and Gram-negative bacteria.
      These efforts toward the rational design of isomeric anagrams of a well-known
      sleep aid underscore the possibility that further optimization of the imidazo[1,2
      a]pyridine core may well "put TB to rest".

PMID- 25984568
TI  - Structural Genomics Support for Infectious Disease Drug Design.

PMID- 25984567
TI  - A Potent Anti-influenza Compound Blocks Fusion through Stabilization of the
      Prefusion Conformation of the Hemagglutinin Protein.
AB  - An ultrahigh-throughput screen was performed to identify novel small molecule
      inhibitors of influenza virus replication. The screen employed a recombinant
      influenza A/WSN/33 virus expressing Renilla luciferase and yielded a hit rate of
      0.5%, of which the vast majority showed little cytotoxicity at the inhibitory
      concentration. One of the top hits from this screen, designated S20, inhibits HA
      mediated membrane fusion. S20 shows potent antiviral activity (IC50 = 80 nM) and
      low toxicity (CC50 = 40 MUM), yielding a selectivity index of 500 and
      functionality against all of the group 1 influenza A viruses tested in this
      study, including the pandemic H1N1 and avian H5N1 viruses. Mechanism of action
      studies proved a direct S20-HA interaction and showed that S20 inhibits fusion by
      stabilizing the prefusion conformation of HA. In silico docking studies were
      performed, and the predicted binding site in HA2 corresponds with the area where
      resistance mutations occurred and correlates with the known role of this region
      in fusion. This high-throughput screen has yielded many promising new lead
      compounds, including S20, which will potentially shed light on the molecular
      mechanisms of viral infection and serve as research tools or be developed for
      clinical use as antivirals.

PMID- 25984569
TI  - Nanomanufacturing of Tobacco Mosaic Virus-Based Spherical Biomaterials Using a
      Continuous Flow Method.
AB  - Nanomanufacturing of nanoparticles is critical for potential translation and
      commercialization. Continuous flow devices can alleviate this need through
      unceasing production of nanoparticles. Here we demonstrate the scaled-up
      production of spherical nanoparticles functionalized with biomedical cargos from
      the rod-shaped plant virus tobacco mosaic virus (TMV) using a mesofluidic,
      continued flow method. Production yields were increased 30-fold comparing the
      mesofluidic device versus batch methods. Finally, we produced MRI contrast agents
      of select sizes, with per particle relaxivity reaching 979,218 mM-1 s-1 at 60
      MHz. These TMV-based spherical nanoparticle MRI contrast agents are in the top
      echelon of relaxivity per nanoparticle.

PMID- 25984570
TI  - 3D Printing with Nucleic Acid Adhesives.
AB  - By relying on specific DNA:DNA interactions as a "smart glue", we have assembled
      microparticles into a colloidal gel that can hold its shape. This gel can be
      extruded with a 3D printer to generate centimeter size objects. We show four
      aspects of this material: (1) The colloidal gel material holds its shape after
      extrusion. (2) The connectivity among the particles is controlled by the binding
      behavior between the surface DNA and this mediates some control over the
      microscale structure. (3) The use of DNA-coated microparticles dramatically
      reduces the cost of DNA-mediated assembly relative to conventional DNA
      nanotechnologies and makes this material accessible for macroscale applications.
      (4) This material can be assembled under biofriendly conditions and can host
      growing cells within its matrix. The DNA-based control over organization should
      provide a new means of engineering bioprinted tissues.

PMID- 25984573
TI  - Lyophilized Silk Sponges: A Versatile Biomaterial Platform for Soft Tissue
      Engineering.
AB  - We present a silk biomaterial platform with highly tunable mechanical and
      degradation properties for engineering and regeneration of soft tissues such as,
      skin, adipose, and neural tissue, with elasticity properties in the kilopascal
      range. Lyophilized silk sponges were prepared under different process conditions
      and the effect of silk molecular weight, concentration and crystallinity on 3D
      scaffold formation, structural integrity, morphology, mechanical and degradation
      properties, and cell interactions in vitro and in vivo were studied. Tuning the
      molecular weight distribution (via degumming time) of silk allowed the formation
      of stable, highly porous, 3D scaffolds that held form with silk concentrations as
      low as 0.5% wt/v. Mechanical properties were a function of silk concentration and
      scaffold degradation was driven by beta-sheet content. Lyophilized silk sponges
      supported the adhesion of mesenchymal stem cells throughout 3D scaffolds, cell
      proliferation in vitro, and cell infiltration and scaffold remodeling when
      implanted subcutaneously in vivo.

PMID- 25984575
TI  - Multivariate Voronoi Outlier Detection for Time Series.
AB  - Outlier detection is a primary step in many data mining and analysis
      applications, including healthcare and medical research. This paper presents a
      general method to identify outliers in multivariate time series based on a
      Voronoi diagram, which we call Multivariate Voronoi Outlier Detection (MVOD). The
      approach copes with outliers in a multivariate framework, via designing and
      extracting effective attributes or features from the data that can take
      parametric or nonparametric forms. Voronoi diagrams allow for automatic
      configuration of the neighborhood relationship of the data points, which
      facilitates the differentiation of outliers and non-outliers. Experimental
      evaluation demonstrates that our MVOD is an accurate, sensitive, and robust
      method for detecting outliers in multivariate time series data.

PMID- 25984574
TI  - The Statistical Modeling of Aging and Risk of Transition Project: Data Collection
      and Harmonization Across 11 Longitudinal Cohort Studies of Aging, Cognition, and
      Dementia.
AB  - Longitudinal cognitive trajectories and other factors associated with mixed
      neuropathologies (such as Alzheimer's disease with co-occurring cerebrovascular
      disease) remain incompletely understood, despite being the rule and not the
      exception in older populations. The Statistical Modeling of Aging and Risk of
      Transition study (SMART) is a consortium of 11 different high-quality
      longitudinal studies of aging and cognition (N=11,541 participants) established
      for the purpose of characterizing risk and protective factors associated with
      subtypes of age-associated mixed neuropathologies (N=3,001 autopsies). While
      brain donation was not required for participation in all SMART cohorts, most
      achieved substantial autopsy rates (i.e., > 50%). Moreover, the studies
      comprising SMART have large numbers of participants who were followed from intact
      cognition and transitioned to cognitive impairment and dementia, as well as
      participants who remained cognitively intact until death. These data provide an
      exciting opportunity to apply sophisticated statistical methods, like Markov
      processes, that require large, well-characterized samples. Thus, SMART will serve
      as an important resource for the field of mixed dementia epidemiology and
      neuropathology.

PMID- 25984571
TI  - Nanotherapy for Cancer: Targeting and Multifunctionality in the Future of Cancer
      Therapies.
AB  - Cancer continues to be a prevalent and lethal disease, despite advances in tumor
      biology research and chemotherapy development. Major obstacles in cancer
      treatment arise from tumor heterogeneity, drug resistance, and systemic
      toxicities. Nanoscale delivery systems, or nanotherapies, are increasing in
      importance as vehicles for antineoplastic agents because of their potential for
      targeting and multifunctionality. We discuss the current field of cancer therapy
      and potential strategies for addressing obstacles in cancer treatment with
      nanotherapies. Specifically, we review the strategies for rationally designing
      nanoparticles for targeted, multimodal delivery of therapeutic agents.

PMID- 25984576
TI  - Organizing the space and behavior of semantic models.
AB  - Semantic models play an important role in cognitive science. These models use
      statistical learning to model word meanings from co-occurrences in text corpora.
      A wide variety of semantic models have been proposed, and the literature has
      typically emphasized situations in which one model outperforms another. However,
      because these models often vary with respect to multiple sub-processes (e.g.,
      their normalization or dimensionality-reduction methods), it can be difficult to
      delineate which of these processes are responsible for observed performance
      differences. Furthermore, the fact that any two models may vary along multiple
      dimensions makes it difficult to understand where these models fall within the
      space of possible psychological theories. In this paper, we propose a general
      framework for organizing the space of semantic models. We then illustrate how
      this framework can be used to understand model comparisons in terms of individual
      manipulations along sub-processes. Using several artificial datasets we show how
      both representational structure and dimensionality-reduction influence a model's
      ability to pick up on different types of word relationships.

PMID- 25984572
TI  - Design strategies and applications of circulating cell-mediated drug delivery
      systems.
AB  - Drug delivery systems, particularly nanomaterial-based drug delivery systems,
      possess a tremendous amount of potential to improve diagnostic and therapeutic
      effects of drugs. Controlled drug delivery targeted to a specific disease is
      designed to significantly improve the pharmaceutical effects of drugs and reduce
      their side effects. Unfortunately, only a few targeted drug delivery systems can
      achieve high targeting efficiency after intravenous injection, even with the
      development of numerous surface markers and targeting modalities. Thus,
      alternative drug and nanomedicine targeting approaches are desired. Circulating
      cells, such as erythrocytes, leukocytes, and stem cells, present innate disease
      sensing and homing properties. Hence, using living cells as drug delivery
      carriers has gained increasing interest in recent years. This review highlights
      the recent advances in the design of cell-mediated drug delivery systems and
      targeting mechanisms. The approaches of drug encapsulation/conjugation to cell
      carriers, cell-mediated targeting mechanisms, and the methods of controlled drug
      release are elaborated here. Cell-based "live" targeting and delivery could be
      used to facilitate a more specific, robust, and smart payload distribution for
      the next-generation drug delivery systems.

PMID- 25984577
TI  - Retraction Notice to: A Self-Produced Trigger for Biofilm Disassembly that
      Targets Exopolysaccharide.

PMID- 25984578
TI  - Michael A. Peters, M.D., 1943 to 2014.

PMID- 25984579
TI  - Robert "Chris" Wray, M.D., 1938 to 2013.

PMID- 25984580
TI  - In memory of Jean-Louis Luche.

PMID- 25984581
TI  - 2015 Alzheimer's disease facts and figures.
AB  - This report discusses the public health impact of Alzheimer's disease (AD),
      including incidence and prevalence, mortality rates, costs of care and the
      overall effect on caregivers and society. It also examines the challenges
      encountered by health care providers when disclosing an AD diagnosis to patients
      and caregivers. An estimated 5.3 million Americans have AD; 5.1 million are age
      65 years, and approximately 200,000 are age <65 years and have younger onset AD.
      By mid-century, the number of people living with AD in the United States is
      projected to grow by nearly 10 million, fueled in large part by the aging baby
      boom generation. Today, someone in the country develops AD every 67 seconds. By
      2050, one new case of AD is expected to develop every 33 seconds, resulting in
      nearly 1 million new cases per year, and the estimated prevalence is expected to
      range from 11 million to 16 million. In 2013, official death certificates
      recorded 84,767 deaths from AD, making AD the sixth leading cause of death in the
      United States and the fifth leading cause of death in Americans age 65 years.
      Between 2000 and 2013, deaths resulting from heart disease, stroke and prostate
      cancer decreased 14%, 23% and 11%, respectively, whereas deaths from AD increased
      71%. The actual number of deaths to which AD contributes (or deaths with AD) is
      likely much larger than the number of deaths from AD recorded on death
      certificates. In 2015, an estimated 700,000 Americans age 65 years will die with
      AD, and many of them will die from complications caused by AD. In 2014, more than
      15 million family members and other unpaid caregivers provided an estimated 17.9
      billion hours of care to people with AD and other dementias, a contribution
      valued at more than $217 billion. Average per-person Medicare payments for
      services to beneficiaries age 65 years with AD and other dementias are more than
      two and a half times as great as payments for all beneficiaries without these
      conditions, and Medicaid payments are 19 times as great. Total payments in 2015
      for health care, long-term care and hospice services for people age 65 years with
      dementia are expected to be $226 billion. Among people with a diagnosis of AD or
      another dementia, fewer than half report having been told of the diagnosis by
      their health care provider. Though the benefits of a prompt, clear and accurate
      disclosure of an AD diagnosis are recognized by the medical profession,
      improvements to the disclosure process are needed. These improvements may require
      stronger support systems for health care providers and their patients.

PMID- 25984583
TI  - Direct C-N Coupling in an in Situ Ligand Transformation and the Self-Assembly of
      a Tetrametallic [Ni(II)4] Staircase.
AB  - A [Ni(II)4] staircase complex was serendipitously prepared from the reaction of
      the binucleating Schiff base proligand 2,6-bis[[(3-hydroxypropyl)imino]methyl]-4
      methylphenol (H3L2) and 3,5-dimethylpyrazole (Me2pzH) with nickel(II) nitrate in
      a reaction at room temperature, initially aimed to yield a dinuclear complex.
      From a room temperature metal ion/ligand reaction, the proligand H3L2 in situ
      transformed to modified forms HL3(2-) and HL4(2-), allowing the [Ni4] formation.
      Variable-temperature magnetic behavior of a [Ni4] complex reveals
      antiferromagnetic interactions with stabilization of a diamagnetic ground state
      (ST = 0). 

PMID- 25984584
TI  - Validation of the Arabic Rowland Universal Dementia Assessment Scale (A-RUDAS) in
      elderly with mild and moderate dementia.
AB  - OBJECTIVES: Validated screening tests for dementia in Arabic are lacking. Given
      the low levels of education among elderly in the Middle East and North Africa
      region, the commonly used screening instrument, the Mini Mental State
      Examination, is not best suited. Alternatively, the Rowland Universal Dementia
      Assessment Scale (RUDAS) was especially designed to minimize the effects of
      cultural learning and education. The aim of this study was to validate the RUDAS
      in the Arabic language (A-RUDAS), evaluate its ability to screen for mild and
      moderate dementia, and assess the effect of education, sex, age, depression, and
      recruitment site on its performance. METHODS: A-RUDAS was administered to 232
      elderly aged >=65 years recruited from the communities, community-based primary
      care clinics, and hospital-based specialist clinics. Of these, 136 had normal
      cognition, and 96 had dementia. Clinicians diagnosed dementia according to the
      Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV)
      criteria. Interviewers, blind to the cognitive status of participants,
      administered A-RUDAS. The psychometric properties of A-RUDAS were examined for
      three cutoffs. RESULTS: At the cutoff of <=22, A-RUDAS exhibited good sensitivity
      (83%) and specificity (85%) with an area under the receiver operating
      characteristic curve of 83.95%. Adjusting for age, sex, education, depression,
      and recruitment site, A-RUDAS score demonstrated a high level of accuracy in
      screening for mild and moderate dementia against DSM-IV diagnosis. CONCLUSION:
      The A-RUDAS is proposed for dementia screening in clinical practice and in
      research in Arabic-speaking populations with an optimal cutoff of <=22.

PMID- 25984582
TI  - Slc5a8, a Na+-coupled high-affinity transporter for short-chain fatty acids, is a
      conditional tumour suppressor in colon that protects against colitis and colon
      cancer under low-fibre dietary conditions.
AB  - Mammalian colon harbours trillions of bacteria under physiological conditions;
      this symbiosis is made possible because of a tolerized response from the mucosal
      immune system. The mechanisms underlying this tolerogenic phenomenon remain
      poorly understood. In the present study we show that Slc5a8 (solute carrier gene
      family 5a, member 8), a Na(+)-coupled high-affinity transporter in colon for the
      bacterial fermentation product butyrate, plays a critical role in this process.
      Among various immune cells in colon, dendritic cells (DCs) are unique not only in
      their accessibility to luminal contents but also in their ability to induce
      tolerogenic phenotype in T-cells. We found that DCs exposed to butyrate express
      the immunosuppressive enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and aldehyde
      dehydrogenase 1A2 (Aldh1A2), promote conversion of naive T-cells into
      immunosuppressive forkhead box P3(+) (FoxP3(+)) Tregs (regulatory T-cells) and
      suppress conversion of naive T-cells into pro-inflammatory interferon (IFN)-gamma
      producing cells. Slc5a8-null DCs do not induce IDO1 and Aldh1A2 and do not
      generate Tregs or suppress IFN-gamma-producing T-cells in response to butyrate.
      We also provide in vivo evidence for an obligatory role for Slc5a8 in suppression
      of IFN-gamma-producing T-cells. Furthermore, Slc5a8 protects against colitis and
      colon cancer under conditions of low-fibre intake but not when dietary fibre
      intake is optimal. This agrees with the high-affinity nature of the transporter
      to mediate butyrate entry into cells. We conclude that Slc5a8 is an obligatory
      link between dietary fibre and mucosal immune system via the bacterial metabolite
      butyrate and that this transporter is a conditional tumour suppressor in colon
      linked to dietary fibre content. 

PMID- 25984585
TI  - Predrinking, alcohol use, and breath alcohol concentration: A study of young
      adult bargoers.
AB  - Predrinking (preloading, pregaming) has been found to be related to alcohol use
      and intoxication. However, most research relies on estimates of blood alcohol
      concentration and does not control for usual drinking pattern. We assessed
      whether predrinking was associated with subsequent alcohol consumption and breath
      alcohol concentration (BrAC) among 287 young adult bargoers (173 men [60.3%],
      Mage = 21.86 years, SD = 2.55 years) who were recruited in groups in an
      entertainment district of a midsized city in Ontario, Canada. We also examined
      whether predrinking by other group members interacted with individual predrinking
      in relation to amount consumed/BrAC. Adjusting for nesting of individuals within
      groups in hierarchical linear models, predrinkers were found to consume more
      drinks in the bar district and over the entire night compared to nonpredrinkers
      and had higher BrACs at the end of the night controlling for drinking pattern. A
      group- by individual-level interaction revealed that individual predrinking
      predicted higher BrACs for members of groups in which at least half of the group
      had been predrinking but not for members of groups in which less than half had
      been predrinking. This study confirms a direct link of predrinking with greater
      alcohol consumption and higher intoxication levels. Group- by individual-level
      effects suggest that group dynamics may have an important impact on individual
      drinking. Given that predrinking is associated with heavier consumption rather
      than reduced consumption at the bar, initiatives to address predrinking should
      include more effective policies to prevent intoxicated people from entering bars
      and being served once admitted.

PMID- 25984586
TI  - Anions Influence the Relaxation Dynamics of Mono-MU3-OH-Capped Triangular
      Dysprosium Aggregates.
AB  - A family of four Dy3 triangular circular helicates, namely, [Dy3(HL)3(MU3
      OH)(CH3OH)2(H2O)4]Cl1.5(OH)0.5.0.5H2O (1), [Dy3(HL)3(MU3
      OH)(CH3OH)3(H2O)2Cl]Cl.CH3OH (2), [Dy3(HL)3(MU3-OH)(CH3OH)3(H2O)2(NO3)](NO3) (3),
      and [Dy3(HL)3(MU3-OH)(CH3OH)4(ClO4)](ClO4) (4), were assembled by the reaction of
      a new acylhydrazone ligand H3L [(3-hydroxy)-N'-((8-hydroxyquinolin-2
      yl)methylene)picolinohydrazide] with different dysprosium(III) salts. These
      compounds represent the first examples of MU-Oacylhydrazone-bridged triangular
      Dy3 SMMs reported to date. Alternating-current magnetic susceptibility
      measurements revealed that compounds 1 and 2 show typical SMM behavior with the
      occurrence of multiple relaxation processes, whereas frequency-dependent
      relaxation signals without chi" peaks were observed in 3 and 4 under zero dc
      field. Such distinct dynamic behaviors are attributed to the different sizes of
      the terminal coordination solvent/anions (H2O, Cl(-), NO3(-), and ClO4(-) for 1
      4, respectively) at the Dy3 site. Here, similar deviations from the ideal
      monocapped square-antiprismatic (C4v) geometry defined by SHAPE software were
      observed around local Dy centers in 1 and 2, whereas the situation was completely
      different in 3 and 4 as a result of the presence of relatively large anions in
      the limited space defined by three intercrossing rigid hydrazone ligands. 

PMID- 25984587
TI  - In the working memory of the beholder: Art appreciation is enhanced when visual
      complexity is compatible with working memory.
AB  - What shapes art appreciation? Much research has focused on the importance of
      visual features themselves (e.g., symmetry, natural scene statistics) and of the
      viewer's experience and expertise with specific artworks. However, even after
      taking these factors into account, there are considerable individual differences
      in art preferences. Our new result suggests that art preference is also
      influenced by the compatibility between visual properties and the characteristics
      of the viewer's visual system. Specifically, we have demonstrated, using 120
      artworks from diverse periods, cultures, genres, and styles, that art
      appreciation is increased when the level of visual complexity within an artwork
      is compatible with the viewer's visual working memory capacity. The result
      highlights the importance of the interaction between visual features and the
      beholder's general visual capacity in shaping art appreciation.

PMID- 25984588
TI  - Searching for faces of different ages: Evidence for an experienced-based own-age
      detection advantage in adults.
AB  - Previous studies have shown that attention deployment in visual search tasks is
      modulated by face race and emotional expression, with a search asymmetry in favor
      of those faces that are less efficiently discriminated and recognized at the
      individual level (i.e., other-race faces and angry faces). Face age is another
      dimension affecting how faces are remembered, as it has been widely reported that
      young adults show significant deficits in recognizing other-age faces. By
      comparing adults' search efficiency for own- and other-age faces in a visual
      search task in which face age was the target feature we explored whether the
      mirror pattern of detection and recognition effects found for race biases
      generalizes to age biases, and whether search efficiency for adult and nonadult
      faces is modulated by experience accumulated with nonadult faces. Search
      efficiency was greater for adult faces than for infant (Experiment 1) or child
      faces (Experiment 2) in adults with limited experience with infants or children,
      whereas there was no sign of search asymmetry in preschool teachers who have had
      extensive recent experience with children (Experiment 2). Results indicate that
      the influence of age on attention deployment parallels the effects that this face
      attribute has on face recognition, and that both effects are experience-based.

PMID- 25984589
TI  - How far away is that? It depends on you: Perception accounts for the abilities of
      others.
AB  - Perception is believed to scale the world to reflect one's own capabilities for
      action-objects that are more effortful to obtain are perceived as further away.
      Somewhat surprisingly, perception is also influenced by observing another person
      attempt an action, even though others cannot directly alter one's own
      capabilities. It is unknown, however, whether the effects of observation reflect
      a simulation of one acting as if from the perspective of the actor, or whether
      they reflect simulation of the potential effects of the actor on the environment,
      but from the observer's own point of view. In 2 experiments, we had an actor and
      an observer view a scene from opposing viewpoints. Enhancement of the actor's
      capabilities to reach a target object caused the target to appear further from
      the observer. Thus, in addition to indexing one's own capabilities, the
      perceptual system also scales the world to account for the potential effects of
      others.

PMID- 25984590
TI  - Scalable Options for Extended Skill Building Following Didactic Training in
      Cognitive-Behavioral Therapy for Anxious Youth: A Pilot Randomized Trial.
AB  - A sizable gap exists between the availability of evidence-based psychological
      treatments and the number of community therapists capable of delivering such
      treatments. Limited time, resources, and access to experts prompt the need for
      easily disseminable, lower cost options for therapist training and continued
      support beyond initial training. A pilot randomized trial tested scalable
      extended support models for therapists following initial training. Thirty-five
      postdegree professionals (43%) or graduate trainees (57%) from diverse
      disciplines viewed an initial web-based training in cognitive-behavioral therapy
      (CBT) for youth anxiety and then were randomly assigned to 10 weeks of expert
      streaming (ES; viewing weekly online supervision sessions of an expert providing
      consultation), peer consultation (PC; non-expert-led group discussions of CBT),
      or fact sheet self-study (FS; weekly review of instructional fact sheets). In
      initial expectations, trainees rated PC as more appropriate and useful to meet
      its goals than either ES or FS. At post, all support programs were rated as
      equally satisfactory and useful for therapists' work, and comparable in
      increasing self-reported use of CBT strategies (b = .19, p = .02). In contrast,
      negative linear trends were found on a knowledge quiz (b = -1.23, p = .01) and
      self-reported beliefs about knowledge (b = -1.50, p < .001) and skill (b = -1.15,
      p < .001). Attrition and poor attendance presented a moderate concern for PC, and
      ES was rated as having the lowest implementation potential. Preliminary findings
      encourage further development of low-cost, scalable options for continued support
      of evidence-based training.

PMID- 25984591
TI  - The effects of intravenous lipid emulsion on prolongation of survival in a rat
      model of calcium channel blocker toxicity.
AB  - CONTEXT: Intravenous lipid emulsion (ILE) has been shown to ameliorate the
      toxicity of lipid-soluble agents in animal studies and clinical cases.
      OBJECTIVES: To investigate the therapeutic effects of ILE in a rat model of
      toxicity from calcium channel blockers (CCBs), including diltiazem and
      nicardipine. METHODS: Two sets of experiments of CCB poisoning were conducted. In
      the first set, 14 male Sprague-Dawley rats were sedated and treated with ILE or
      normal saline (NS), followed by continuous intravenous infusion of diltiazem (20
      mg/kg/h). In the second experiment, the study protocol was the same except the
      infusion of nicardipine (20 mg/kg/h). The total dose of infused drug and the
      duration of survival were measured. In addition, mean arterial pressure and heart
      rate were monitored. RESULTS: Survival was prolonged in the ILE group (48.4 +/-
      11.3 vs. 25.0 +/- 3.7 min; p = 0.002). Furthermore, the cumulative mean lethal
      dose of diltiazem was higher in the ILE group (16.1 +/- 3.8 mg/kg) than in the NS
      group (8.3 +/- 1.1 mg/kg) (p = 0.002). With nicardipine poisoning, survival was
      also prolonged in the ILE group (71.0 +/- 8.3 min vs. 30.6 +/- 6.1 min; p =
      0.002). The cumulative mean lethal dose was higher in the ILE group than in the
      NS group (23.7 +/- 2.8 mg/kg vs. 10.2 +/- 2.0 mg/kg; p = 0.002). CONCLUSIONS: ILE
      pretreatment prolonged survival and increased the lethal dose in a rat model of
      CCB poisoning using diltiazem and nicardipine.

PMID- 25984592
TI  - Radical Instability in Aid of Efficiency: A Powerful Route to Highly Functional
      MIDA Boronates.
AB  - The inability of the sp(3) boron in MIDA boronates to stabilize an adjacent
      radical makes possible the efficient addition of a wide array of xanthates to
      vinyl MIDA boronate, leading to highly functionalized and diverse aliphatic
      organoboron structures. The lack of radical stabilization also allows the
      exchange of the xanthate in the adducts with a bromine. In one case, the bromine
      was substituted to generate a cyclopropyl MIDA derivative. 

PMID- 25984593
TI  - Proanthocyanidins and Their Contribution to Sensory Attributes of Black Currant
      Juices.
AB  - Black currant juices from five different cultivars were analyzed for composition,
      content, and mean degree of polymerization (mDP) of proanthocyanidins (PA) by
      UPLC-MS/MS. Juices contained both procyanidins (PC) and prodelphinidins (PD), but
      the PC-% varied significantly, from 28 to 82% of the total PA. In addition, high
      PD-% was related to high mDP and total PA content. Enzyme-assisted processing
      increased significantly total PA (5-14-fold), PD-% (12-65%), and mDP (1.8-6.2
      fold) in the juices of all cultivars. Enzymatic treatment increased the contents
      of large PAs more than those of small PAs. The contents of PA and mDP were
      positively associated with the mouth-drying and puckering astringent
      characteristics. However, the PA content did not contribute to the bitter taste.
      Juices from the most bitter cultivars had the lowest contents of
      proanthocyanidins regardless of the processing method. This finding indicates the
      existence of other bitter compounds in black currants in addition to PA. 

PMID- 25984594
TI  - A genetic tool kit for cellular and behavioral analyses of insect sugar
      receptors.
AB  - Arthropods employ a large family of up to 100 putative taste or gustatory
      receptors (Grs) for the recognition of a wide range of non-volatile chemicals. In
      Drosophila melanogaster, a small subfamily of 8 Gr genes is thought to mediate
      the detection of sugars, the fly's major nutritional source. However, the
      specific roles for most sugar Gr genes are not known. Here, we report the
      generation of a series of mutant sugar Gr knock-in alleles and several composite
      sugar Gr mutant strains, including a sugar blind strain, which will facilitate
      the characterization of this gene family. Using Ca(2+) imaging experiments, we
      show that most gustatory receptor neurons (GRNs) of sugar blind flies (lacking
      all 8 sugar Gr genes) fail to respond to any sugar tested. Moreover, expression
      of single sugar Gr genes in most sweet GRNs of sugar-blind flies does not restore
      sugar responses. However, when pair-wise combinations of sugar Gr genes are
      introduced to sweet GRNs, responses to select sugars are restored. We also
      examined the cellular phenotype of flies homozygous mutant for Gr64a, a Gr gene
      previously reported to be a major contributor for the detection of many sugars.
      In contrast to these claims, we find that sweet GRNs of Gr64a homozygous mutant
      flies show normal responses to most sugars, and only modestly reduced responses
      to maltose and maltotriose. Thus, the precisely engineered genetic mutations of
      single Gr genes and construction of a sugar-blind strain provide powerful
      analytical tools for examining the roles of Drosophila and other insect sugar Gr
      genes in sweet taste. 

PMID- 25984595
TI  - Viscoelastic Emulsion Improved the Bioaccessibility and Oral Bioavailability of
      Crystalline Compound: A Mechanistic Study Using in Vitro and in Vivo Models.
AB  - The oral bioavailability of hydrophobic compound is usually limited by the poor
      aqueous solubility in the gastrointestinal (GI) tract. Various oral formulations
      were developed to enhance the systemic concentration of such molecules. Moreover,
      compounds with high melting temperature that appear as insoluble crystals imposed
      a great challenge to the development of oral vehicle. Polymethoxyflavone, an
      emerging category of bioactive compounds with potent therapeutic efficacies, were
      characterized as having a hydrophobic and highly crystalline chemical structure.
      To enhance the oral dosing efficiency of polymethoxyflavone, a viscoelastic
      emulsion system with a high static viscosity was developed and optimized using
      tangeretin, one of the most abundant polymethoxyflavones found in natural
      sources, as a modeling compound. In the present study, different in vitro and in
      vivo models were used to mechanistically evaluate the effect of emulsification on
      oral bioavailability of tangeretin. In vitro lipolysis revealed that emulsified
      tangeretin was digested and became bioaccessible much faster than unprocessed
      tangeretin oil suspension. By simulating the entire human GI tract, TNO's
      gastrointestinal model (TIM-1) is a valuable tool to mechanistically study the
      effect of emulsification on the digestion events that lead to a better oral
      bioavailability of tangeretin. TIM-1 result indicated that tangeretin was
      absorbed in the upper GI tract. Thus, a higher oral bioavailability can be
      expected if the compound becomes bioaccessible in the intestinal lumen soon after
      dosing. In vivo pharmacokinetics analysis on mice again confirmed that the oral
      bioavailability of tangeretin increased 2.3 fold when incorporated in the
      viscoelastic emulsion than unformulated oil suspension. By using the combination
      of in vitro and in vivo models introduced in this work, the mechanism that
      underlie the effect of viscoelastic emulsion on the oral bioavailability of
      tangeretin was well-elucidated. 

PMID- 25984596
TI  - Organocatalytic Asymmetric Michael/Friedel-Crafts Cascade Reaction of 3-Pyrrolyl
      oxindoles and alpha,beta-Unsaturated Aldehydes for the Construction of Chiral
      Spiro[5,6-dihydropyrido[1,2-a]pyrrole-3,3'-oxindoles].
AB  - An efficient and unprecedented organocatalytic asymmetric reaction of 3-pyrrolyl
      oxindoles with alpha,beta-unsaturated aldehydes to generate spirocyclic oxindole
      compounds was developed. The reactions were catalyzed by diphenylprolinol silyl
      ether and 2-fluorobenzoic acid via an asymmetric Michael/Friedel-Crafts cascade
      process, followed by dehydration with p-toluenesulfonic acid to afford a wide
      variety of structurally diverse spiro[5,6-dihydropyrido[1,2-a]pyrrole-3,3'
      oxindole] derivatives in high yields (up to 93%) and with high to excellent
      diastereo- and enantioselectivities (up to >99:1 dr and 97% ee). 

PMID- 25984597
TI  - In Situ Observations of Thermoreversible Gelation and Phase Separation of Agarose
      and Methylcellulose Solutions under High Pressure.
AB  - Thermoreversible sol-gel transitions of agarose and methylcellulose (MC) aqueous
      solutions on isobaric cooling or heating under high pressure up to 400 MPa have
      been investigated by in situ observations of optical transmittance and falling
      ball experiments. For agarose, which undergoes the gelation on cooling, the
      application of pressure caused a gradual rise in the cloud-point temperature over
      the whole pressure range examined, which is almost consistent with the pressure
      dependence of gelling temperature estimated by falling-ball experiments,
      suggesting that agarose gel is stabilized by compression and that the gelation
      occurs nearly in parallel with phase separation under ambient and high-pressure
      conditions. For MC, which undergoes the gelation on heating, the cloud-point
      temperature showed a slight rise with an initial elevation of pressure up to ~150
      MPa, whereas it showed a marked depression above 200 MPa. In contrast, the
      gelling temperature of MC, which is nearly identical to the cloud-point
      temperature at ambient pressure, showed a monotonous rise with increasing
      pressure up to 350 MPa, which means that MC undergoes phase separation prior to
      gelation on heating under high pressure above 200 MPa. Similar results were
      obtained for the melting process of MC gel on cooling. The unique behavior of the
      sol-gel transition of MC under high pressure has been interpreted in terms of the
      destruction of hydrophobic hydration by compression. 

PMID- 25984598
TI  - One-pot exfoliation of graphite and synthesis of nanographene/dimesitylporphyrin
      hybrids.
AB  - A simple one-pot process to exfoliate graphite and synthesize nanographene
      dimesitylporphyrin hybrids has been developed. Despite the bulky mesityl groups,
      which are expected to hinder the efficient pi-pi stacking between the porphyrin
      core and graphene, the liquid-phase exfoliation of graphite is significantly
      favored by the presence of the porphyrins. Metallation of the porphyrin further
      enhances this effect. The resulting graphene/porphyrin hybrids were characterized
      by spectroscopy (UV-visible, fluorescence, and Raman) and microscopy (STEM,
      scanning transmission electron microscopy). 

PMID- 25984599
TI  - The multi-biomarker approach for heart failure in patients with hypertension.
AB  - We assessed the predictive ability of selected biomarkers using N-terminal pro
      brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a
      multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120
      hypertensive patients with or without overt heart failure, the incremental
      predictive value of the following biomarkers was investigated: Collagen III N
      terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4,
      tumor necrosis factor-alpha (TNF-alpha), interleukin 1 receptor type I (IL1R1),
      galectin-3, cardiotrophin-1 (CT-1), transforming growth factor beta (TGF-beta)
      and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest
      discriminative value for HF was observed for NT-proBNP (area under the receiver
      operating characteristic curve (AUC)=0.873) and TGF-beta (AUC=0.878). On the
      basis of ROC curve analysis we found that CT-1>152 pg/mL, TGF-beta<7.7 ng/mL,
      syndecan>2.3 ng/mL, NT-proBNP>332.5 pg/mL, CysC>1 mg/L and NGAL>39.9 ng/mL were
      significant predictors of overt HF. There was only a small improvement in
      predictive ability of the multi-biomarker panel including the four biomarkers
      with the best performance in the detection of HF-NT-proBNP, TGF-beta, CT-1, CysC
      compared to the panel with NT-proBNP, TGF-beta and CT-1 only. Biomarkers with
      different pathophysiological backgrounds (NT-proBNP, TGF-beta, CT-1, CysC) give
      additive prognostic value for incident HF in hypertensive patients compared to NT
      proBNP alone.

PMID- 25984600
TI  - Ultrasound assessment of carotid plaque echogenicity response to statin therapy:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate in a systematic review and meta-analysis model the effect
      of statin therapy on carotid plaque echogenicity assessed by ultrasound. METHODS:
      We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and
      Cochrane Center Register) up to April, 2015, for studies evaluating the effect of
      statins on plaque echogenicity. Two researchers independently determined the
      eligibility of studies evaluating the effect of statin therapy on carotid plaque
      echogenicity that used ultrasound and grey scale median (GSM) or integrated back
      scatter (IBS). RESULTS: Nine out of 580 identified studies including 566
      patients' carotid artery data were meta-analyzed for a mean follow up of 7.2
      months. A consistent increase in the echogenicity of carotid artery plaques,
      after statin therapy, was reported. Pooled weighted mean difference % (WMD) on
      plaque echogenicity after statin therapy was 29% (95% CI 22%-36%), p<0.001,
      I2=92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and
      hsCRP as moderators, it was shown that the effects of statins on plaque
      echogenicity were related to changes in hsCRP, but not to LDL and HDL changes
      from the baseline. The effect of statins on the plaque was progressive; it showed
      significance after the first month of treatment, and the echogenicity continued
      to increase in the following six and 12 months. CONCLUSIONS: Statin therapy is
      associated with a favorable increase of carotid plaque echogenicity. This effect
      seems to be dependent on the period of treatment and hsCRP change from the
      baseline, independent of changes in LDL and HDL.

PMID- 25984602
TI  - Theoretical in-Solution Conformational/Tautomeric Analyses for Chain Systems with
      Conjugated Double Bonds Involving Nitrogen(s).
AB  - Conformational/tautomeric transformations for X=CH-CH=Y structures (X = CH2, O,
      NH and Y = NH) have been studied in the gas phase, in dichloromethane and in
      aqueous solutions. The paper is a continuation of a former study where s-cis/s
      trans conformational equilibria were predicted for analogues. The s-trans
      conformation is preferred for the present molecules in the gas phase on the basis
      of its lowest internal free energy as calculated at the B97D/aug-cc-pvqz and
      CCSD(T)CBS (coupled-cluster singles and doubles with non-iterative triples
      extrapolated to the complete basis set) levels. Transition state barriers are of
      29-36 kJ/mol for rotations about the central C-C bonds. In solution, an s-trans
      form is still favored on the basis of its considerably lower internal free energy
      compared with the s-cis forms as calculated by IEF-PCM (integral-equation
      formalism of the polarizable continuum dielectric solvent model) at the
      theoretical levels indicated. A tetrahydrate model in the supermolecule/continuum
      approach helped explore the 2solute-solvent hydrogen bond pattern. The calculated
      transition state barrier for rotation about the C-C bond decreased to 27 kJ/mol
      for the tetrahydrate. Considering explicit solvent models, relative solvation
      free energies were calculated by means of the free energy perturbation method
      through Monte Carlo simulations. These calculated values differ remarkably from
      those by the PCM approach in aqueous solution, nonetheless the same prevalent
      conformation was predicted by the two methods. Aqueous solution structure
      characteristics were determined by Monte Carlo. Equilibration of
      conformers/tautomers through water-assisted double proton-relay is discussed.
      This mechanism is not viable, however, in non-protic solvents where the
      calculated potential of mean force curve does not predict remarkable solute
      dimerization and subsequent favorable orientation. 

PMID- 25984601
TI  - Caffeic Acid phenethyl ester is a potential therapeutic agent for oral cancer.
AB  - Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per
      year, is the sixth leading cancer by cancer incidence and eighth by cancer
      related death worldwide. Oral cancer is the most common type of head and neck
      cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell
      carcinoma (OSCC). The overall five-year survival rate of OSCC patients is
      approximately 63%, which is due to the low response rate to current therapeutic
      drugs. In this review we discuss the possibility of using caffeic acid phenethyl
      ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong
      antioxidant extracted from honeybee hive propolis. Recent studies indicate that
      CAPE treatment can effectively suppress the proliferation, survival, and
      metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell
      cycle regulatory proteins, NF-kappaB function, as well as activity of matrix
      metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and
      Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and
      apoptosis in oral cancer cells. According to the evidence that aberrations in the
      EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-kappaB
      function, COX-2 activity, and MMPs activity are frequently found in oral cancers,
      and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer
      patient survival and clinical progression, we believe that CAPE treatment will be
      useful for treatment of advanced oral cancer patients. 

PMID- 25984604
TI  - Preparation and in vivo evaluation of a dutasteride-loaded solid-supersaturatable
      self-microemulsifying drug delivery system.
AB  - The purpose of this study was to prepare a dutasteride-loaded solid
      supersaturatable self-microemulsifying drug delivery system (SMEDDS) using
      hydrophilic additives with high oral bioavailability, and to determine if there
      was a correlation between the in vitro dissolution data and the in vivo
      pharmacokinetic parameters of this delivery system in rats. A dutasteride-loaded
      solid-supersaturatable SMEDDS was generated by adsorption of liquid SMEDDS onto
      Aerosil 200 colloidal silica using a spray drying process. The dissolution and
      oral absorption of dutasteride from solid SMEDDS significantly increased after
      the addition of hydroxypropylmethyl cellulose (HPMC) or Soluplus. Solid
      SMEDDS/Aerosil 200/Soluplus microparticles had higher oral bioavailability with
      6.8- and 5.0-fold higher peak plasma concentration (Cmax) and area under the
      concentration-time curve (AUC) values, respectively, than that of the equivalent
      physical mixture. A linear correlation between in vitro dissolution efficiency
      and in vivo pharmacokinetic parameters was demonstrated for both AUC and Cmax
      values. Therefore, the preparation of a solid-supersaturatable SMEDDS with HPMC
      or Soluplus could be a promising formulation strategy to develop novel solid
      dosage forms of dutasteride. 

PMID- 25984603
TI  - Chemical reactions directed Peptide self-assembly.
AB  - Fabrication of self-assembled nanostructures is one of the important aspects in
      nanoscience and nanotechnology. The study of self-assembled soft materials
      remains an area of interest due to their potential applications in biomedicine.
      The versatile properties of soft materials can be tuned using a bottom up
      approach of small molecules. Peptide based self-assembly has significant impact
      in biology because of its unique features such as biocompatibility, straight
      peptide chain and the presence of different side chain functionality. These
      unique features explore peptides in various self-assembly process. In this
      review, we briefly introduce chemical reaction-mediated peptide self-assembly.
      Herein, we have emphasised enzymes, native chemical ligation and photochemical
      reactions in the exploration of peptide self-assembly. 

PMID- 25984605
TI  - Optimization of catheter ablation of atrial fibrillation: insights gained from
      clinically-derived computer models.
AB  - Atrial fibrillation (AF) is the most common heart rhythm disturbance, and its
      treatment is an increasing economic burden on the health care system. Despite
      recent intense clinical, experimental and basic research activity, the treatment
      of AF with current antiarrhythmic drugs and catheter/surgical therapies remains
      limited. Radiofrequency catheter ablation (RFCA) is widely used to treat patients
      with AF. Current clinical ablation strategies are largely based on atrial anatomy
      and/or substrate detected using different approaches, and they vary from one
      clinical center to another. The nature of clinical ablation leads to ambiguity
      regarding the optimal patient personalization of the therapy partly due to the
      fact that each empirical configuration of ablation lines made in a patient is
      irreversible during one ablation procedure. To investigate optimized ablation
      lesion line sets, in silico experimentation is an ideal solution. 3D computer
      models give us a unique advantage to plan and assess the effectiveness of
      different ablation strategies before and during RFCA. Reliability of in silico
      assessment is ensured by inclusion of accurate 3D atrial geometry, realistic
      fiber orientation, accurate fibrosis distribution and cellular kinetics; however,
      most of this detailed information in the current computer models is extrapolated
      from animal models and not from the human heart. The predictive power of computer
      models will increase as they are validated with human experimental and clinical
      data. To make the most from a computer model, one needs to develop 3D computer
      models based on the same functionally and structurally mapped intact human atria
      with high spatial resolution. The purpose of this review paper is to summarize
      recent developments in clinically-derived computer models and the clinical
      insights they provide for catheter ablation. 

PMID- 25984606
TI  - Prediction of protein-protein interactions with clustered amino acids and
      weighted sparse representation.
AB  - With the completion of the Human Genome Project, bioscience has entered into the
      era of the genome and proteome. Therefore, protein-protein interactions (PPIs)
      research is becoming more and more important. Life activities and the protein
      protein interactions are inseparable, such as DNA synthesis, gene transcription
      activation, protein translation, etc. Though many methods based on biological
      experiments and machine learning have been proposed, they all spent a long time
      to learn and obtained an imprecise accuracy. How to efficiently and accurately
      predict PPIs is still a big challenge. To take up such a challenge, we developed
      a new predictor by incorporating the reduced amino acid alphabet (RAAA)
      information into the general form of pseudo-amino acid composition (PseAAC) and
      with the weighted sparse representation-based classification (WSRC). The
      remarkable advantages of introducing the reduced amino acid alphabet is being
      able to avoid the notorious dimensionality disaster or overfitting problem in
      statistical prediction. Additionally, experiments have proven that our method
      achieved good performance in both a low- and high-dimensional feature space.
      Among all of the experiments performed on the PPIs data of Saccharomyces
      cerevisiae, the best one achieved 90.91% accuracy, 94.17% sensitivity, 87.22%
      precision and a 83.43% Matthews correlation coefficient (MCC) value. In order to
      evaluate the prediction ability of our method, extensive experiments are
      performed to compare with the state-of-the-art technique, support vector machine
      (SVM). The achieved results show that the proposed approach is very promising for
      predicting PPIs, and it can be a helpful supplement for PPIs prediction. 

PMID- 25984607
TI  - Borrowing nuclear DNA helicases to protect mitochondrial DNA.
AB  - In normal cells, mitochondria are the primary organelles that generate energy,
      which is critical for cellular metabolism. Mitochondrial dysfunction, caused by
      mitochondrial DNA (mtDNA) mutations or an abnormal mtDNA copy number, is linked
      to a range of human diseases, including Alzheimer's disease, premature aging and
      cancer. mtDNA resides in the mitochondrial lumen, and its duplication requires
      the mtDNA replicative helicase, Twinkle. In addition to Twinkle, many DNA
      helicases, which are encoded by the nuclear genome and are crucial for nuclear
      genome integrity, are transported into the mitochondrion to also function in
      mtDNA replication and repair. To date, these helicases include RecQ-like helicase
      4 (RECQ4), petite integration frequency 1 (PIF1), DNA replication
      helicase/nuclease 2 (DNA2) and suppressor of var1 3-like protein 1 (SUV3).
      Although the nuclear functions of some of these DNA helicases have been
      extensively studied, the regulation of their mitochondrial transport and the
      mechanisms by which they contribute to mtDNA synthesis and maintenance remain
      largely unknown. In this review, we attempt to summarize recent research progress
      on the role of mammalian DNA helicases in mitochondrial genome maintenance and
      the effects on mitochondria-associated diseases. 

PMID- 25984610
TI  - [The role of alexithymia as a psychosomatic factor in psoriasis].
AB  - BACKGROUND: Alexithymia is the lack of mental representations of emotions leading
      to limited ability to understand and regulate these and can contribute to the
      development or maintenance of a psychosomatic illness. The aim of the study was
      to demonstrate that alexithymia is a feature that occurs more frequently in
      patients with psoriasis and that the coexistence of alexitimia-psoriasis is
      associated with high levels of trait anxiety. METHODS: We applied the Toronto
      Alexithymia Scale -20 (TAS-20), Inventory of state-trait anxiety (STAI) to 16
      outpatients with psoriasis of Dermatology Service of Hospital de Especialidades
      (Centro Medico Nacional Siglo XXI) and the results were compared with 25 control
      subjects. RESULTS: 25 % of patients with psoriasis presented alexitimia, while in
      the control group was 8 % (p = 0.002). Correlation between the scores of the TSA
      20 and STAI-trait (r = 0.6957, p < 0.0001) was observed. CONCLUSIONS: The
      alexitimia occurs more frequently in individuals with psoriasis than in the
      general population, and levels of trait anxiety in individuals with psoriasis are
      similar regardless of the presence of alexithymia.

PMID- 25984609
TI  - Possibility of breast cancer prevention: use of soy isoflavones and fermented soy
      beverage produced using probiotics.
AB  - The various beneficial effects of soybeans, which are rich in phytochemicals,
      have received much attention because of increasing health awareness. Soy milk
      that has been fermented using lactic acid bacteria has been used to prepare
      cheese-like products, tofu (bean-curd), and yogurt-type products. However, the
      distinct odor of soybeans has limited the acceptance of such foods, particularly
      in Western countries. In Japan, while tofu and soy milk have long been habitually
      consumed, the development of novel, palatable food products has not been easy.
      The unpleasant odor of soy milk and the absorption efficiency for isoflavones can
      be improved using a recently developed fermented soy milk beverage. Cancer has
      been the leading cause of death, and breast cancer is the most common malignancy
      among women. The most common type of breast cancer is estrogen-dependent, and the
      anti-estrogenic effects of isoflavones are known. The present review focuses on
      the characteristics of soy milk fermented using probiotics, an epidemiological
      study examining the incidence of breast cancer and soy isoflavone consumption,
      and a non-clinical study examining breast cancer prevention using fermented soy
      milk beverage. 

PMID- 25984608
TI  - Potential anti-cancer activities and mechanisms of costunolide and
      dehydrocostuslactone.
AB  - Costunolide (CE) and dehydrocostuslactone (DE) are derived from many species of
      medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have
      been reported for their wide spectrum of biological effects, including anti
      inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant,
      antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have
      caused extensive interest in researchers due to their potential anti-cancer
      activities for various types of cancer, and their anti-cancer mechanisms,
      including causing cell cycle arrest, inducing apoptosis and differentiation,
      promoting the aggregation of microtubule protein, inhibiting the activity of
      telomerase, inhibiting metastasis and invasion, reversing multidrug resistance,
      restraining angiogenesis has been studied. This review will summarize anti-cancer
      activities and associated molecular mechanisms of these two compounds for the
      purpose of promoting their research and application. 

PMID- 25984611
TI  - [Locally administered ropivacaine vs. standard analgesia for laparoscopic
      cholecystectomy].
AB  - BACKGROUND: It is unknown which analgesic modality gives better results after a
      laparoscopic cholecystectomy. The aim of this study was to compare the analgesic
      efficacy of ropivacaine for local use against that of intravenous dipyrone in
      laparoscopic cholecystectomy. METHODS: A non-inferiority randomized clinical
      trial. Fifty patients with laparoscopic cholecystectomy were included into two
      separate groups. INTERVENTION: 0.75 % ropivacaine infiltrated at the trocar
      insertion sites and in the gallbladder fossa compared with intravenous dipyrone.
      MEASUREMENTS: The primary outcome was pain, which was assessed using the visual
      analog scale during the first 24 hours. Secondary outcomes were the presence of
      adverse effects, and the need for analgesic rescue with tramadol. RESULTS: The
      visual analog scale average for pain at the conclusion of the surgery was 3.8 in
      the ropivacaine vs. 3.56 in the dipyrone groups, while at 6, 12 and 24 hours the
      values were 2.64, 1.92 and 1.28, respectively, for ropivacaine versus 2.6, 1.88
      and 1.2, respectively, for dipyrone. No adverse effects were observed in either
      group, and the two groups exhibited similar needs for analgesic rescue with
      tramadol. CONCLUSIONS: Infiltration of 0.75 % ropivacaine at the trocar insertion
      sites and the gallbladder exhibits analgesia similar to IV dipyrone during the
      first 24 hours post-laparoscopic cholecystectomy without adverse effects.

PMID- 25984612
TI  - [Endoscopic third ventriculostomy for chronic communicating hydrocephalus in
      adults].
AB  - BACKGROUND: Shunt devices to treat hydrocephalus are associated with a
      malfunction of 81 % at 12 years and 10 % of infection. The objective was to
      assess safeness and efficacy of endoscopic third ventriculostomy (ETV) for the
      treatment of chronic communicating hydrocephalus. METHODS: Eight patients with
      chronic communicating hydrocephalus were included in a period between September,
      2012 and April, 2013. X ray computed tomography scans were performed when
      patients were admitted, after the surgery, and at 30, 180 and 365 days. The
      follow-up was of 251 days (the biggest was of 459 days). The variables included
      were: age, sex, etiology, time of evolution, and the total number of shunt
      malfunctions. Conventional technique with a 30 degrees  rigid endoscope was
      performed, malfunctional shunt was removed, and a tied shunt device was placed.
      RESULTS: Four males and four females, with a mean age of 42 years (27-63 years);
      neurocysticercosis was identified in five patients (62.5 %); the evolution rate
      was of 18 years (15-30 years); the hospital stay rate was of 6.5 days (3-22
      days); the mean of previous shunt malfunctions was 4 (1-6). COMPLICATIONS:
      neuroinfection in one patient, malfunction in three patients. None of them died.
      CONCLUSIONS: ETV is a safety procedure for treating chronic communicating
      hydrocephalus; it has a success rate higher than 60 %. Neurocysticercosis showed
      better results when previous shunt malfunctions were lower than three.

PMID- 25984613
TI  - [Cytomegalovirus: congenital infection and clinical presentation in infants with
      respiratory distress syndrome].
AB  - BACKGROUND: Respiratory distress syndrome (RDS) is a multifactorial and common
      disease that varies from 15 to 50 % in the newborn, causing 50 % of mortality.
      The RDS may be associated with bacterial and viral infections, and one of the
      most common viral agents is the cytomegalovirus (CMV). In the neonatal period the
      virus incidence goes from 0.4 to 2.5 % with a seroprevalence of 50 to 75 %; the
      incidence of infection in newborn with RDS is unknown. The objective was to
      determine the frequency of CMV infection in neonates with RDS and identify the
      risk factors associated with infection. METHODS: The CMV-DNA was identified in
      plasma by quantitative PCR; maternal and neonatal variables that defined the
      clinical findings were analyzed by logistic regression.The CMV-DNA was identified
      in plasma by quantitative PCR; maternal and neonatal variables that defined the
      clinical findings were analyzed by logistic regression. RESULTS: The frequency of
      CMV infection in 197 infants with RDS was 8.6 % (95 % CI, 4.7-12.5). The
      significant variables in newborn were: neutropenia (p = 0.012), thrombocytopenia
      (p = 0.021), mottled skin (p = 0.03), and the maternal significant variable was
      cervicovaginitis (p = 0.05). CONCLUSIONS: We reported for the first time the
      highest frecuency of CMV infection in newborns with RDS and the association of
      various risk factors with CMV infection.

PMID- 25984614
TI  - [Bibliometric analysis of scientific output on influenza in Mexico, 2000-2012].
AB  - BACKGROUND: During the spring of 2009, H1N1 influenza became the first pandemic
      of the 21st century. There are no bibliometric studies in Mexico that have
      analyzed this topic in relation to the generation of Mexican knowledge. The aim
      of this article is to determine the volume and impact of Mexican scientific
      output published in journals indexed in Science Citation Index (SCI) on influenza
      from January 1, 2000, to October 1, 2012. METHODS: All the documents within SCI
      whose topic was influenza were included; in order to do this, we used the
      describers influenza or swine flu H1N1. The analysis included authorship,
      international collaboration, journals, document type, citations and address of
      correspondence. RESULTS: In 2000-2012, 241 articles related to influenza were
      published. The years with the highest number of articles were 2009 (n = 53) and
      2010 (n = 62). The journals with the highest quantity of papers were Salud
      Publica de Mexico (n = 16), PLOS ONE (n = 13), Archives of Medical Research (n =
      13) and Vaccine (n = 10). The most investigated area was infectious diseases
      (18.9 %), followed by internal medicine (14 %) and immunology (14 %),
      occupational health (13 %) and experimental medicine (12.3 %). CONCLUSION: The
      scientific output on influenza supposes near 1 % of the total of the medical
      scientific production with a decline posterior to the outbreak of 2009 pandemic
      influenza.

PMID- 25984615
TI  - [Relationship between body fat and creatinine clearence in adults with and
      without diabetes mellitus].
AB  - BACKGROUND: Obesity is a risk factor for renal damage. This study aimed to
      determine the relationship between body fat percent and creatinine clearance in
      adult patients with and without type 2 diabetes mellitus (T2DM). METHODS: An
      observational prospective cross-correlation study was carried out among adults
      with and without T2DM between 18 and 60 years of age. It was determined the time
      of evolution with T2DM, as well as fat percentage (FP), body mass index (BMI),
      creatinine clearance (Cockroft-Gault [CrCCG]), glycemia and
      micro/macroalbuminuria. The correlation between CrCCG and FP was determined by
      Spearman's test. RESULTS: 174 subjects were included in this study. Obesity by
      BMI and FP in subjects with and without T2DM was similar. Of the studied
      subjects, 12.6 % didn't have kidney damage and 50.7 % had increased risk of renal
      disease; the frequencies for stages 1-4 of kidney damage were 12.0, 20.1, 4.0 and
      0.6 %, respectively. Spearman's test showed a direct relationship between FP and
      CrCCG, higher in diabetics (r = 0.418, p < 0.0001) than in non-diabetics (p =
      0.327, p < 0.0001). CONCLUSIONS: The FP was correlated directly with the CrCCG in
      subjects with and without T2DM; therefore, we can conclude that the greater the
      kidney damage, the smaller the fat porcentage in the study sample.

PMID- 25984616
TI  - [Cultural domain of the causes of diabetes in three generations of popular
      stratum in Guadalajara, Mexico].
AB  - BACKGROUND: The growing prevalence of diabetes must be confronted in several
      ways. Establishing the generational transmission of cultural knowledge offers
      some guidelines to prevent and control the disease. Once we identify and compare
      the semantic structures of shared knowledge we lay the foundations of a
      culturally comprehensive care. The objective was to characterize the main
      elements about cultural domain of the causes of diabetes in a population of
      grandparents, parents and children belonging to popular strata in Guadalajara,
      Jalisco, Mexico. METHODS: A cognitive anthropological study performed in 104
      subjects selected randomly in Guadalajara. We applied the free listing technique
      in order to obtain the semantic model and the average of cultural knowledge on
      the causes of the disease through a consensus analysis.A cognitive
      anthropological study performed in 104 subjects selected randomly in Guadalajara.
      We applied the free listing technique in order to obtain the semantic model and
      the average of cultural knowledge on the causes of the disease through a
      consensus analysis. RESULTS: The studied groups were divided by generation:
      grandparents, parents and children. The data evidences intergenerational
      transmission, in form of a basic semantic structure, and a significant consensus
      around a single model. CONCLUSIONS: The semantic structure on the causes of the
      diabetes includes: a) the emotions, as traditional dimension; b) certain
      behaviours related with the lifestyle, as everyday dimension; c) some biomedical
      concepts, like an emergent dimension.

PMID- 25984617
TI  - [Lactate levels as a predictor of mortality in patients with septic shock].
AB  - BACKGROUND: The objective was to determine the association between serum lactate
      levels and mortality in patients with septic shock in the Emergency Room of the
      Instituto Mexicano del Seguro Social's Centro Medico Nacional Adolfo Ruiz
      Cortines. METHODS: We included the patients admitted to the Emergency Room with
      diagnosis of septic shock who had measure of serum lactate at admission during
      the period 01-12/2013; it was a case-control study. The cut-off value of serum
      lactate associated with mortality was performed using the ROC (receiver operating
      characteristic) curves. RESULTS: Sixty-seven patients were studied, out of which
      56 survived (cases) and 11 died (controls). There was no association with gender,
      age and comorbidities. The cut-off value for mortality of serum lactate was 4.9
      mmol/L. Ten patients out of 40 with lactate levels > 4.9 mmol/L, and only one out
      of 27 with lactate < 4.9 mmol/L died (p = 0.04); odds ratio was of 8.7. The
      mortality in patients with septic shock and lactate > 4.9 mmol/ is high and had a
      sensitivity of 90.9 % and specificity of 46.4 %. CONCLUSIONS: The levels of serum
      lactate greater than four are associated to an increased risk of mortality in
      patients with septic shock.

PMID- 25984618
TI  - [Bibliometric analysis of Revista Medica del IMSS in the Scopus database for the
      period between 2005-2013].
AB  - OBJECTIVE: To analyze the number of articles of Revista Medica del Instituto
      Mexicano del Seguro Social (Rev Med Inst Mex Seguro Soc) in the Scopus database
      and describe principal quantitative bibliometric indicators of scientific
      publications during the period between 2005 to 2013. METHODS: Scopus database was
      used limited to the period between 2005 to 2013. The analysis cover mainly title
      of articles with the title of Revista Medica del Instituto Mexicano del Seguro
      Social and its possible modifications. For the analysis, Scopus, Excel and Access
      were used. RESULTS: 864 articles were published during the period between 2005 to
      2013 in the Scopus database. We identified authors with the highest number of
      contributions including articles with the highest citation rate and forms of
      documents cited. We also divided articles by subjects, types of documents and
      other bibliometric indicators which characterize the publications. CONCLUSIONS:
      The use of Scopus brings the possibility of analyze with an external tool the
      visibility of the scientific production published in the Revista Medica del IMSS.
      The use of this database also contributes to identify the state of science in
      Mexico, as well as in the developing countries.

PMID- 25984619
TI  - [Socioeconomic inequality and health in Mexico].
AB  - OBJECTIVE: To establish the relationship between socioeconomic inequality and
      health problems amongst Mexican population reviewing studies with national or
      regional representation. METHODS: A literature search was performed at national
      and international databases using the following keywords: health, disease, mental
      disorders, nutrition, food, social class, social status, unemployment,
      employment, occupation, income, wage, poverty and socioeconomic status. Reports
      of national or regional surveys conducted from the nineties were included.
      RESULTS: Mostly, diseases events were more common among people from low
      socioeconomic status: anencephaly, viral infections, anemia, transit accidents by
      run over, metabolic syndrome, hypertension, affective disorder, anxiety and
      substances abuse; some malignancies, difficulties to perform activities of daily
      living, and poor perceived health status. On the opposite, as it goes down in the
      social scale, are less frequent some protective factors (e.g. fruits or
      vegetables intake and physical activity) and there is less access to medical aid
      and preventive interventions (e.g. condom use or diagnosis and treatment for HIV
      infection, hypertension or obesity). CONCLUSIONS: Socioeconomic status affects
      all living conditions; therefore, its effects are not confined to certain
      diseases, but a general precarious state of health. The conceptual and public
      policy implications related with social inequalities in health are discussed.

PMID- 25984620
TI  - [Copy number variation: markers and predictors for type 2 diabetes].
AB  - Type 2 diabetes (T2D) is a disease characterized by a deficiency in production or
      action of insulin. It is the result mainly of the interaction of the environment,
      lifestyle, as well as genetic factors. It is considered as one of the major
      health issues in the world because it affects severely the psychological well
      being and overall life quality. Recently it has been shown that DNA copy number
      variations (CNVs) are associated with several diseases, including obesity and
      T2D. The CNVs are present from 9 to 18 % of the genome and can modify the
      expression levels of mRNA and proteins encoded by genes located near their
      localization. Less is known about their contribution to the pathogenesis of
      metabolic diseases, which is necessary to characterize so that these variations
      can be potentially used as biomarkers of genetic risk CNVs of T2D. 

PMID- 25984621
TI  - [Overview of sharps injuries among health-care workers].
AB  - Sharps injuries are one of the most frequent health-care related accidents. It is
      estimated globally that 35 million workers are at risk; in Mexico there is no
      data available for this type of injuries. They are associated with lack of
      training, instrument and procedure risk, fatigue and stress. The occupational
      distribution is nurses 45 %, technicians 20 %, doctors 20 % and maintenance
      workers 5 %. The most commonly associated procedures are injection, venipuncture,
      suture, and insertion and manipulation of IV catheters. Hepatitis B is the most
      commonly transmitted agent. Emotional distress is huge as well as the cost of
      prophylaxis and follow-up. More than half of the injuries are not notified. The
      most common reasons for not reporting are: the belief that the exposure has low
      risk of infection, the lack of knowledge of reporting systems and the assumption
      that it is difficult to notify. Many strategies have been created to reduce the
      incidence of sharps injuries, such as: identifying the risk of blood exposure,
      the creation of politics to minimize the risk, the education and training to
      create a safe workplace, the enhancing of the reporting system, the use of double
      gloving and using safety-engineered sharps devices. In many countries these
      politics have reduced the incidence of sharps injuries as well as the economic
      burden. 

PMID- 25984622
TI  - [Association between anxiety and coping strategies employed by primary caregivers
      of bedridden patients].
AB  - BACKGROUND: The primary caregiver faces a set of problems derived from the
      responsibility to provide care to his patient; this leads to the creation of
      complex psychological responses that act as a mechanism known as cognitive and
      behavioral coping. The objective was to determine if there was a correlation
      between the level of anxiety and the coping strategies used by primary caregivers
      of bedridden patients. METHODS: Transversal, descriptive and correlational study.
      Beck Anxiety Inventory and the Coping Strategies Inventory were used. We used
      Spearman's rank correlation coefficient, a significance level of 0.05 and the
      statistical program SPSS, version 15. RESULTS: We included 60 primary caregivers.
      The most common score for anxiety was moderate (28 %). The most frequently used
      strategy was problem solving (average = 14.7). By relating the level of anxiety
      and coping strategies a significant correlation was obtained with problem
      solving: r = 0.260; self-criticism, r = 0.425; wishful thinking, r = 0.412; and
      social withdrawal, r = 0.453. CONCLUSIONS: The anxiety has an impact on the way
      caregivers cope; most of the population who have moderate to severe anxiety use
      desadaptive strategies focused on emotion.

PMID- 25984623
TI  - [Breast self-examination in users of the Instituto Mexicano del Seguro Social
      from Teapa, Tabasco, Mexico].
AB  - OBJECTIVE: To establish the proportion of women of 40 years-old and more, which
      perform properly breast self-examination in the Family Medical Unit 18 of the
      Instituto Mexicano del Seguro Social from Teapa, Tabasco, Mexico, in 2011.
      METHODS: Cross-sectional study in a universe of 1457 women. A random sample of
      127 women was obtained and aleatorily selected. Socio-demographic and hereditary
      variables were included and breast self-examination technique was evaluated. The
      information was taken from clinical files and check lists. Descriptive statistic
      was obtained. RESULTS: The mean age was 52.7 +/- 9.3, with a confidence interval
      of 40-80 years-old. Women with a primary-school education were the largest group,
      representing 35.4 %. Family antecedent of breast malign tumor was found in 11 %.
      The mother was the most frequent parent with this background (42.9 %). Adequate
      breast self-examination technique was observed in 0.8 %. CONCLUSIONS: The
      proportion of women that performs breast self-examination properly is very low.
      Associated factors were not found. Educative interventions are required in order
      to correct this problem.

PMID- 25984624
TI  - [Onychomycosis frequency in psoriatic patients in a tertiary care hospital].
AB  - BACKGROUND: The changes in psoriatic nails can closely resemble an onychomycosis.
      Therefore, the fungal infection may be underdiagnosed. It was investigated the
      frequency of mycosis in fingernails and toenails in 150 patients with psoriasis
      in a dermatology department. METHODS: The clinical data suggestive of
      onychomycosis were investigated. Nail scales were obtained and cultured on
      Sabouraud dextrose agar with and without antibiotic. A direct examination with
      KOH was also performed. RESULTS: Out of 150 patients, 67 (45 %) had healthy
      nails; 42 (28 %) presented onychomycosis and 41 (27 %) showed nail changes
      without infection. Fingernail changes were more associated with psoriatic
      onychopathy (82.5 %), unlike toenail changes that were more frequently caused by
      fungal infection (26.4 % vs. 9.45 % in psoriasis). Out of 20 positive cultures,
      22 fungi were isolated, of which 11 belonged to Candida spp. (50 %). As risk
      factor to develope an onychomycosis, only the psoriasis evolution time showed a
      significant difference (p = 0.033). CONCLUSIONS: In patients with psoriasis,
      fingernail disorders are mainly due to the own disease, while toenail disorders
      changes can be associated with onychomycosis. The main etiological agents were
      yeasts from the genus Candida. The only factor associated with a higher incidence
      of onychomycosis in these patients was a long lasting psoriasis.

PMID- 25984625
TI  - [Quality of life in chronic obstructive lung disease. Experience in a hospital
      from Western Mexico].
AB  - BACKGROUND: The chronic obstructive lung disease (COPD) is a common, expensive
      and preventable disease, and the evaluation of the quality of life in patients
      with the condition widens the scope of the results in their attention. The
      objective was to evaluate the health related quality of life (HRQL) according to
      the severity of the COPD. METHODS: Descriptive study. Patients with COPD
      diagnosis according with the severity and related with the HRQL measured using a
      specific questionnaire. Statistical analyses were made using c2 or ANOVA in ranks
      according with the variables. A p value = 0.05 was considered significant.
      RESULTS: 62 patients were included; 61% women. HRQL questionnaire showed the
      Activity dimension as the more negatively affected (65 +/- 24 points, p < 0.05).
      In the Impact dimension, severity groups III and IV were more affected compared
      with groups I and II (p < 0.05). There was a directly correlation between a
      better FEV1 with better HRQL results (r2-0.544 p < 0.0001). CONCLUSIONS: HRQL is
      affected and clinically meaningful in patients with a major severity degree of
      the COPD condition. The parameters that better predicts a worst HRQL was % FEV1
      and FVC.

PMID- 25984626
TI  - Cement dust exposition and bronchioalveolitis. A case report.
AB  - The goal of the current investigation was to report an unusual case of a worker
      acutely exposed to big amounts of cement dust. This exposure caused chemical
      bronchioalveolitis and dermatitis due to chromium contact. This person suffered
      the exposure when a cement deposit exploded at work. This exposed the worker to
      big amounts of cement dust. After the accident, the individual suffered dyspnea
      and bilateral basal pulmonary crackles. The subject also presented an atypical
      restrictive pattern, which could also be seen on X-rays as 1/1 q/q images of the
      classification of 2000 of the International Labour Organization (ILO), and a
      bulging of a pulmonary artery. A restrictive pattern pure atypical was observed,
      and arterial blood gas with hipoxemia. A treatment with steroids was prescribed
      and the worker showed some improvement. There is high risk of developing
      pulmonary fibrosis with the progressive evolution in stages of the
      bronchioalveolitis, even when the subject is isolated. Therefore, it would be
      very convenient to create a specialized medical center where workers that have
      this kind of accidents can have the proper care by qualified personnel. 

PMID- 25984627
TI  - [A tribute to Carl Djerassi].
AB  - On January 15, 2015, Carl Djerassi, an extraordinary personality, died at the age
      of 91 years. He was born in Vienna, Austria, on October 29, 1923. His parents
      were physicians and probably he wanted to be also a physician, but sooner than
      later he chose to be a chemist. In 1939 he arrived to live to New York with his
      mother. In 1945 he became American citizen. Part of his work is the first
      commercial antihistamine, pyribenzamine, and the first successful combined oral
      contraceptive pill. With this editorial we make a tribute to this steroid
      pioneer. 

PMID- 25984628
TI  - [Neither chikungunya nor chikunguna: chicunguna].

PMID- 25984629
TI  - [Response to the comment "neither chikungunya nor chikunguna: chicunguna"].

PMID- 25984630
TI  - [Comment on "genomics in medicine"].

PMID- 25984631
TI  - [Answer to comments regarding the article "genomics in medicine"].

PMID- 25984633
TI  - Photoalignment of an azobenzene-based chromonic liquid crystal dispersed in
      triacetyl cellulose: single-layer alignment films with an exceptionally high
      order parameter.
AB  - Single-layer thin alignment films of dye molecules are of growing importance,
      particularly for state-of-the-art LCD technology. Here we show that a sequential
      process involving the photoalignment and humidification of a chromonic liquid
      crystalline azobenzene (brilliant yellow; BY) dispersed in a triacetyl cellulose
      (TAC) matrix gives a thin alignment film with an exceptionally high order
      parameter (0.81). Spectroscopic and X-ray diffraction analyses of a BY/TAC
      composite film in each alignment process revealed that brief humidification
      triggers restructuring of the BY assembly from 1D nematic-like order to
      anisotropic 2D columnar order, resulting in the dramatic increase in the order
      parameter. 

PMID- 25984632
TI  - Glucagon-Like Peptide-1 Regulates Cholecystokinin Production in beta-Cells to
      Protect From Apoptosis.
AB  - Cholecystokinin (CCK) is a classic gut hormone that is also expressed in the
      pancreatic islet, where it is highly up-regulated with obesity. Loss of CCK
      results in increased beta-cell apoptosis in obese mice. Similarly, islet alpha
      cells produce increased amounts of another gut peptide, glucagon-like peptide 1
      (GLP-1), in response to cytokine and nutrient stimulation. GLP-1 also protects
      beta-cells from apoptosis via cAMP-mediated mechanisms. Therefore, we
      hypothesized that the activation of islet-derived CCK and GLP-1 may be linked. We
      show here that both human and mouse islets secrete active GLP-1 as a function of
      body mass index/obesity. Furthermore, GLP-1 can rapidly stimulate beta-cell CCK
      production and secretion through direct targeting by the cAMP-modulated
      transcription factor, cAMP response element binding protein (CREB). We find that
      cAMP-mediated signaling is required for Cck expression, but CCK regulation by
      cAMP does not require stimulatory levels of glucose or insulin secretion. We also
      show that CREB directly targets the Cck promoter in islets from obese
      (Leptin(ob/ob)) mice. Finally, we demonstrate that the ability of GLP-1 to
      protect beta-cells from cytokine-induced apoptosis is partially dependent on CCK
      receptor signaling. Taken together, our work suggests that in obesity, active GLP
      1 produced in the islet stimulates CCK production and secretion in a paracrine
      manner via cAMP and CREB. This intraislet incretin loop may be one mechanism
      whereby GLP-1 protects beta-cells from apoptosis.

PMID- 25984634
TI  - The Relationship between MX [3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)
      furanone], Routinely Monitored Trihalomethanes, and Other Characteristics in
      Drinking Water in a Long-Term Survey.
AB  - MX (3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) is a drinking water
      disinfection byproduct (DBP). It is a potent mutagen and is of concern to public
      health. Data on MX levels in drinking water, especially in the UK, are limited.
      Our aim was to investigate factors associated with variability of MX
      concentrations at the tap, and to evaluate if routinely measured trihalomethanes
      (THMs) are an appropriate proxy measure for MX. We conducted quarterly water
      sampling at consumers' taps in eight water supply zones in and around Bradford,
      UK, between 2007 and 2010. We collected 79 samples which were analyzed for MX
      using GC-HRMS. Other parameters such as pH, temperature, UV-absorbance and free
      chlorine were measured concurrently, and total THMs were modeled from regulatory
      monitoring data. To our knowledge this is the longest MX measurement survey
      undertaken to date. Concentrations of MX varied between 8.9 and 45.5 ng/L with a
      median of 21.3 ng/L. MX demonstrated clear seasonality with concentrations
      peaking in late summer/early fall. Multivariate regression showed that MX levels
      were associated with total trihalomethanes, UV-absorbance and pH. However, the
      relationship between TTHM and MX may not be sufficiently consistent across time
      and location for TTHM to be used as a proxy measure for MX in exposure
      assessment. 

PMID- 25984636
TI  - A combined analysis of the Frost Multidimensional Perfectionism Scale (FMPS),
      Child and Adolescent Perfectionism Scale (CAPS), and Almost Perfect Scale-Revised
      (APS-R): Different perfectionist profiles in adolescent high school students.
AB  - To investigate differences and similarities in the dimensional constructs of the
      Frost Multidimensional Perfectionism Scale (FMPS; Frost, Marten, Lahart, &
      Rosenblate, 1990), Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt,
      Boucher, Davidson, & Munro, 2000), and Almost Perfect Scale-Revised (APS-R;
      Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 938 high school students completed
      the 3 perfectionism questionnaires, as well as the Depression Anxiety Stress
      Scales (DASS; Lovibond & Lovibond, 1995). Preliminary analyses revealed commonly
      observed factor structures for each perfectionism questionnaire. Exploratory
      factor analysis of item responses from the questionnaires (combined) yielded a 4
      factor solution (factors were labeled High Personal Standards, Concerns, Doubts
      and Discrepancy, Externally Motivated Perfectionism, and Organization and Order).
      A latent class analysis of individuals' mean ratings on each of the 4 factors
      yielded a 6-class solution. Three of the 6 classes represented perfectionist
      subgroups (labeled adaptive perfectionist, externally motivated maladaptive
      perfectionist, and mixed maladaptive perfectionist), and 3 represented
      nonperfectionist subgroups (labeled nonperfectionist A, nonperfectionist B, and
      order and organization nonperfectionist). Each of the 6 subgroups was
      meaningfully associated with the DASS. Findings showed that 3 out of 10 students
      were classified as maladaptive perfectionists, and maladaptive perfectionists
      were more prevalent than adaptive perfectionists. In sum, it is evident that
      combined ratings from the FMPS, CAPS, and APS-R offer a meaningful
      characterization of perfectionism.

PMID- 25984635
TI  - Trait-based assessment of borderline personality disorder using the NEO Five
      Factor Inventory: Phenotypic and genetic support.
AB  - [Correction Notice: An Erratum for this article was reported in Vol 28(1) of
      Psychological Assessment (see record 2015-54029-001). The FFI-BPD values for
      Sample 3 in Table 2 should read 1.42 (0.44), 0.83.] The aim of the current study
      was to examine the reliability and validity of a trait-based assessment of
      borderline personality disorder (BPD) using the NEO Five-Factor Inventory.
      Correlations between the Five-Factor Inventory-BPD composite (FFI-BPD) and
      explicit measures of BPD were examined across 6 samples, including undergraduate,
      community, and clinical samples. The median correlation was .60, which was nearly
      identical to the correlation between measures of BPD and a BPD composite
      generated from the full Revised NEO Personality Inventory (i.e., NEO-BPD; r =
      .61). Correlations between FFI-BPD and relevant measures of psychiatric
      symptomatology and etiology (e.g., childhood abuse, drug use, depression, and
      personality disorders) were also examined and compared to those generated using
      explicit measures of BPD and NEO-BPD. As expected, the FFI-BPD composite
      correlated most strongly with measures associated with high levels of
      Neuroticism, such as depression, anxiety, and emotion dysregulation, and the
      pattern of correlations generated using the FFI-BPD was highly similar to those
      generated using explicit measures of BPD and NEO-BPD. Finally, genetic analyses
      estimated that FFI-BPD is 44% heritable, which is comparable to meta-analytic
      research examining genetics associated with BPD, and revealed that 71% of the
      genetic influences are shared between FFI-BPD and a self-report measure assessing
      BPD (Personality Assessment Inventory-Borderline subscale; Morey, 1991).
      Generally, these results support the use of FFI-BPD as a reasonable proxy for
      BPD, which has considerable implications, particularly for potential gene-finding
      efforts in large, epidemiological datasets that include the NEO FFI.

PMID- 25984637
TI  - The dark side of gendered language: The masculine-generic form as a cause for
      self-report bias.
AB  - Language reflects sociocultural structures, such as gender, and affects
      individuals' perceptions and cognitions. In gendered languages, male-inflected
      parts of speech are generally used for both sexes (i.e., masculine generics),
      thus proliferating stereotypes, inequality, and misattributions. We hypothesized
      that masculine-generic inflection in a questionnaire would bias women's reports
      compared with a gender-neutral inflection (e.g., "he or she"). We tested our
      prediction using an academic motivation questionnaire. We found that women
      reported lower task value and intrinsic goal orientation in the masculine-generic
      form compared with the gender-neutral form, and lower self-efficacy than men in
      the masculine-generic form. These findings suggest that questionnaires and
      surveys written in gendered languages or translated into them may contain
      construct-irrelevant variance that may undermine the validity of their scores'
      interpretations, thus risking the possibility of false conclusions.

PMID- 25984640
TI  - Palliative care: a specialty focused on the relief of suffering of individuals,
      families, communities, and populations.

PMID- 25984641
TI  - Dying for Advice: Code Status Discussions between Resident Physicians and
      Patients with Advanced Cancer--A National Survey.
AB  - BACKGROUND: Patients with treatment-resistant advanced cancer rarely benefit from
      cardiopulmonary resuscitation (CPR) but infrequently discuss end-of-life care
      with physicians until hospitalized. Admitting resident physicians may conduct
      initial code status discussions, but may elicit patients' preferences without
      providing necessary guidance. OBJECTIVE: We surveyed residents' approach to code
      status discussions to identify barriers hindering informed decision making.
      METHODS: We developed an online case-based survey and enrolled subjects via e
      mail requests to program directors. U.S. internal medicine residents (n=358;
      response rate 22.0%) from 19 programs participated. We measured respondents'
      likelihood of discussing prognosis and benefit of CPR, likelihood of offering
      code status recommendations, preference for discussing code status independent of
      attending physicians, and satisfaction with end-of-life discussions. RESULTS:
      Nearly all residents felt CPR would be unhelpful. Yet fewer than half (46.7%)
      were likely to discuss an estimate of prognosis and the value of CPR with the
      patient. Only 30% were likely to offer a recommendation on CPR. A majority (69%)
      of residents who were unwilling to offer a recommendation stated that deference
      to patient autonomy prevented them from providing guidance. Residents preferred
      to discuss code status independent of attendings, primarily due to a sense of
      responsibility. Ultimately, only a minority was satisfied with end-of-life
      discussions. CONCLUSION: U.S. internal medicine resident physicians are unlikely
      to discuss prognosis or offer recommendations on CPR in treatment-refractory
      cancer principally because of a conflict with their concept of patient autonomy.
      Given the futility associated with CPR in this setting, these data define an
      unmet need in training and practice.

PMID- 25984642
TI  - Highly efficient usage of the hydrothermal technique through the one-pot method
      to construct four Keggin-based compounds containing pendent ligands.
AB  - By utilizing two kinds of pendent organic ligands, four new Keggin-based
      compounds, [Ag(bpz)2(pz)(H2O)(H3PMo12O40)2] (), [Ag(bpz)2(H3PMo12O40)].2H2O (),
      [Ag(btz)4(PMo12O40)] () and [Ag(btz)3(PMo12O40)].H2O () (bpz = 4-butyl-1H
      pyrazole, pz = pyrazole, btz = 1-benzyl-1H-(1,2,4)triazole), were synthesized
      under hydrothermal conditions and characterized by single crystal X-ray
      diffraction. Compounds and were obtained in one-pot reaction, as well as
      compounds and . In compound , six Ag(I) ions are fused by four bpz and two pz
      molecules to form a hexa-nuclear cycle, with two coordinated water embedding
      through Ag-O bonds. The three-connected Mo13-containing PMo12 anions connect
      these cycles alternately to construct 1D chains, which are further linked by four
      connected Mo1-containing PMo12 anions to build a 3D framework of . Compound
      contains 1D Ag(I) chains, linked by four-connected Mo1-containing PMo12 and two
      connected Mo7-containing PMo12 respectively to construct a 3D structure. The pz
      ligand was not observed in . In compound , there exist [Ag(btz)4](3+) subunits,
      which are alternately connected by PMo12 anions to form a 1D chain. In compound ,
      there exists a zigzag Ag-btz chain. The adjacent chains are further linked by Ag
      C bonds and a 2D metal-organic layer is constructed. The PMo12 anions link
      adjacent layers to build a 3D framework of . The syntheses of compounds and , and
      prove that the one-pot method under hydrothermal conditions is efficient for
      pursuing even two more kinds of crystals. 

PMID- 25984638
TI  - Development of a composite trauma exposure risk index.
AB  - The high burden of exposure to chronic life adversities and trauma is quite
      prevalent, but assessment of this risk burden is uncommon in primary care
      settings. This calls for a brief, multiple dimensional mental health risk
      screening tool in primary care settings. We aimed to develop such a screening
      tool named the University of California, Los Angeles (UCLA) Life Adversities
      Screener (LADS). Using pooled data across 4 studies from the UCLA Center for
      Culture, Trauma, and Mental Health Disparities, 5 domains of mental health risk
      including perceived discrimination, sexual abuse histories, family adversity,
      intimate partner violence, and trauma histories, were identified. Regression
      models for depression (Centers for Epidemiology Studies Depression Scale) and
      posttraumatic stress disorder (Posttraumatic Diagnostic Scale), controlling for
      demographic factors, were fitted to develop a weighted continuous scale score for
      the UCLA LADS. Confirmatory factor analysis supported the 5-domain structure,
      while item response theory endorsed the inclusion of each item. Receiver
      operating characteristic analysis indicated that the score was predictive for
      classifying subjects as reaching clinical threshold criteria for either
      depression (Beck Depression Inventory-II >= 14 or Patient Health Questionnaire-9
      >= 10) or anxiety (Patient Health Questionnaire-13 >=10). An optimal cut of 0.33
      is suggested based on maximizing sensitivity and specificity of the LADS score,
      identifying patients at high risk for mental health problems. Given its
      predictive utility and ease of administration, the UCLA LADS could be useful as a
      screener to identify racial minority individuals in primary care settings who
      have a high trauma burden, needing more extensive evaluation.

PMID- 25984643
TI  - Dimensions of driving anger and their relationships with aberrant driving.
AB  - The purpose of this study was to investigate the relationship between driving
      anger and aberrant driving behaviours. An internet-based questionnaire survey was
      administered to a sample of Chinese drivers, with driving anger measured by a 14
      item short Driving Anger Scale (DAS) and the aberrant driving behaviours measured
      by a 23-item Driver Behaviour Questionnaire (DBQ). The results of Confirmatory
      Factor Analysis demonstrated that the three-factor model (hostile gesture,
      arrival-blocking and safety-blocking) of the DAS fitted the driving anger data
      well. The Exploratory Factor Analysis on DBQ data differentiated four types of
      aberrant driving, viz. emotional violation, error, deliberate violation and
      maintaining progress violation. For the anger-aberration relation, it was found
      that only "arrival-blocking" anger was a significant positive predictor for all
      four types of aberrant driving behaviours. The "safety-blocking" anger revealed a
      negative impact on deliberate violations, a finding different from previously
      established positive anger-aberration relation. These results suggest that
      drivers with different patterns of driving anger would show different behavioural
      tendencies and as a result intervention strategies may be differentially
      effective for drivers of different profiles. 

PMID- 25984644
TI  - Temporal patterns of deer-vehicle collisions consistent with deer activity
      pattern and density increase but not general accident risk.
AB  - The increasing number of deer-vehicle collisions (DVCs) across Europe during
      recent decades poses a serious threat to human health and animal welfare and
      increasing costs for society. DVCs are triggered by both a human-related and a
      deer-related component. Mitigation requires an understanding of the processes
      driving temporal and spatial collision patterns. Separating human-related from
      deer-related processes is important for identifying potentially effective
      countermeasures, but this has rarely been done. We analysed two time series of
      341,655 DVCs involving roe deer and 854,659 non-deer-related accidents (non-DVCs)
      documented between 2002 and 2011. Nonparametric smoothing and temporal parametric
      modelling were used to estimate annual, seasonal, weekly and diurnal patterns in
      DVCs, non-DVCs and adjusted DVCs. As we had access to data on both DVCs and non
      DVCs, we were able to disentangle the relative role of human-related and deer
      related processes contributing to the overall temporal DVC pattern. We found
      clear evidence that variation in DVCs was mostly driven by deer-related and not
      human-related activity on annual, seasonal, weekly and diurnal scales. A very
      clear crepuscular activity pattern with high activity after sunset and around
      sunrise throughout the year was identified. Early spring and the mating season
      between mid-July and mid-August are typically periods of high roe deer activity,
      and as expected we found a high number of DVC during these periods, although
      these patterns differed tremendously during different phases of a day. The role
      of human activity was mainly reflected in fewer DVCs on weekends than on
      weekdays. Over the ten-year study period, we estimated that DVCs increased by
      25%, whereas the number of non-DVCs decreased by 10%. Increasing deer densities
      are the most likely driver behind this rise in DVCs. Precise estimates of DVC
      patterns and their relationship to deer and human activity patterns allow
      implementation of specific mitigation measures, such as tailored driver warning
      systems or temporary speed limits. To prevent a further increase in DVCs, state
      wide measures to decrease roe deer density are required. 

PMID- 25984645
TI  - Methodological issues related to pooling results from panel studies of heart rate
      variability and its association with ambient air pollution.
AB  - Reviews of observational studies and subsequent meta-analyses are challenging to
      interpret because of potential methodological issues and biases inherent in
      studies. In reviewing panel studies of the association between heart rate
      variability and ambient air pollution we identified a number of methodological
      issues that make difficult interpreting and pooling findings from longitudinal
      studies, notably issues related to associations arising from different type of
      designs, differences in design characteristics, including study populations,
      measurements of heart rate variability (e.g., duration and condition of the
      electrocardiogram recordings), exposure assessment (e.g., types of monitoring),
      metrics of exposure used, and parameters estimated from regression models. We
      conclude that many panel studies of the association between heart rate
      variability and ambient air pollution may not be comparable to each other, and
      thus caution must be exercised to avoid misleading conclusions. 

PMID- 25984646
TI  - Attention in 3-Year-Old Children with VLBW and Relationships with Early School
      Outcomes.
AB  - AIM: To compare attention skills of children with a very low birth weight (VLBW)
      with children with a normal birth weight (NBW) when entering primary school, and
      explore the association of attention skills with school career 2 years later.
      METHODS: Participants were 151 children with VLBW and 41 with NBW. Attention was
      assessed at 3 years and 8 months of corrected age (CA) and school career at 51/2
      years of CA. Children performed two tests, parents completed three
      questionnaires, and an assessor systematically observed children's attention.
      RESULTS: Children with VLBW had significantly lower mean scores on five of the
      six measures. Significantly more children with VLBW had scores in the clinical
      range on the Child Behavior Checklist completed by the parents (13% versus 0%)
      and scores representing dysfunction on assessor observations (19% versus 2%). At
      51/2 years of age, 36% of the children with VLBW followed special education or
      had grade retention. Dysfunctional attention as observed by the assessor was most
      strongly associated with need for learning support at 51/2 years of age.
      CONCLUSIONS: At preschool age, children with VLBW have attention difficulties.
      Attentive behavior at preschool age is a predictor of school career 2 years
      later.

PMID- 25984649
TI  - Majorana transport in superconducting nanowire with Rashba and Dresselhaus spin
      orbit couplings.
AB  - The tunneling experiment is a key technique for detecting Majorana fermion (MF)
      in solid state systems. We use Keldysh non-equilibrium Green function method to
      study two-lead tunneling in superconducting nanowire with Rashba and Dresselhaus
      spin-orbit couplings. A zero-bias dc conductance peak appears in our setup which
      signifies the existence of MF and is in accordance with previous experimental
      results on InSb nanowire. Interestingly, due to the exotic property of MF, there
      exists a hole transmission channel which makes the currents asymmetric at the
      left and right leads. The ac current response mediated by MF is also studied
      here. To discuss the impacts of Coulomb interaction and disorder on the transport
      property of Majorana nanowire, we use the renormalization group method to study
      the phase diagram of the wire. It is found that there is a topological phase
      transition under the interplay of superconductivity and disorder. We find that
      the Majorana transport is preserved in the superconducting-dominated topological
      phase and destroyed in the disorder-dominated non-topological insulator phase. 

PMID- 25984647
TI  - De Novo Conception of Small Molecule Modulators Based on Endogenous Peptide
      Ligands: Pyrrolodiazepin-2-one gamma-Turn Mimics That Differentially Modulate
      Urotensin II Receptor-Mediated Vasoconstriction ex Vivo.
AB  - A proof-of-concept library of pyrrolodiazepinone small molecules was designed
      based on the Bip-Lys-Tyr motif found in a recently described modulator of the
      urotensinergic system. Solid-phase synthesis provided 13 analogues, which were
      tested for their ability to modulate selectively and differentially the potency
      (EC50) and efficacy (E(max)) of hUII and URP ex vivo in a rat aortic ring
      bioassay. Notably, at 14 MUM, pyrrolodiazepinone R-4a inhibited completely hUII
      induced contractions and increased URP-associated vasoconstriction.
      Pyrrolodiazepinone R-4a represents, to the best of our knowledge, a first-in
      class small molecule that exerts a probe-dependent effect on hUII and URP
      biological activities and proves that UT modulators of the urotensin II receptor
      (UT) can be rationally designed. The importance of the UT system in the
      pathogenesis and progression of cardiovascular diseases highlights the utility of
      pyrrolodiazepinones such as R-4a, which exhibit promising potential as tools for
      differentiating the respective roles, signaling pathways, and phenotypic outcomes
      of UII and URP in the UT system.

PMID- 25984650
TI  - Polymer Surface Engineering for Efficient Printing of Highly Conductive Metal
      Nanoparticle Inks.
AB  - An approach to polymer surface modification using self-assembled layers (SALs) of
      functional alkoxysilanes has been developed in order to improve the printability
      of silver nanoparticle inks and enhance adhesion between the metal conducting
      layer and the flexible polymer substrate. The SALs have been fully characterized
      by AFM, XPS, and WCA, and the resulting printability, adhesion, and electrical
      conductivity of the screen-printed metal contacts have been estimated by cross
      cut tape test and 4-point probe measurements. It was shown that (3
      mercaptopropyl)trimethoxysilane SALs enable significant adhesion improvements for
      both aqueous- and organic-based silver inks, approaching nearly 100% for PEN and
      PDMS substrates while exhibiting relatively low sheet resistance up to 0.1
      Omega/sq. It was demonstrated that SALs containing functional -SH or -NH2 end
      groups offer the opportunity to increase the affinity of the polymer substrates
      to silver inks and thus to achieve efficient patterning of highly conductive
      structures on flexible and stretchable substrates. 

PMID- 25984651
TI  - Periodically Grafted Amphiphilic Copolymers: Effects of Steric Crowding and
      Reversal of Amphiphilicity.
AB  - Two series of periodically clickable polyesters were prepared; one of them
      carries alkylene segments along its backbone, whereas the other carries
      poly(ethylene glycol) (PEG) segments. These polyesters were clicked with either
      MPEG-350 azide or docosyl (C22) azide to yield periodically grafted amphiphilic
      copolymers (PGACs) carrying either flexible hydrophilic or crystallizable
      hydrophobic backbone segments. The immiscibility between hydrocarbon and PEG
      segments causes both of these systems to fold in either a zigzag or hairpin-like
      conformation; the hairpin-like conformation appears to be preferred when flexible
      PEG segments are present in the backbone. The folded chains further reorganize in
      the solid state to develop a lamellar morphology that permits the collocation of
      the PEG and hydrocarbon (HC) segments within alternate domains; evidence for the
      self-segregation was gained from DSC, SAXS, and AFM studies. SAXS studies
      revealed the formation of an extended lamellar structure, whereas AFM images
      showed uniform layered morphology with layer heights that matched reasonably well
      with the interlamellar spacing obtained from the SAXS study. Labeling one
      representative PGAC, carrying crystallizable long alkylene segments in the
      backbone and pendant PEG-350 side chains, with a small mole fraction of pyrene
      fluorophore permitted the examination of the conformational transition that
      occurs upon going from a good to a poor solvent; this single-chain folded
      conformation, we postulate, is the intermediate that organizes into the lamellar
      morphology. 

PMID- 25984653
TI  - Phototherapy with blue and green mixed-light is as effective against unconjugated
      jaundice as blue light and reduces oxidative stress in the Gunn rat model.
AB  - OBJECTIVE: Phototherapy using blue light-emitting diodes (LED) is effective
      against neonatal jaundice. However, green light phototherapy also reduces
      unconjugated jaundice. We aimed to determine whether mixed blue and green light
      can relieve jaundice with minimal oxidative stress as effectively as either blue
      or green light alone in a rat model. METHODS: Gunn rats were exposed to
      phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without<440-nm
      wavelengths, FB50 (half the irradiance of filtered blue), mixed (filtered 50%
      blue and 50% green), and green (490-590 nm) LED irradiation for 24h. The effects
      of phototherapy are expressed as ratios of serum total (TB) and unbound (UB)
      bilirubin before and after exposure to each LED. Urinary 8-hydroxy-2'
      deoxyguanosine (8-OHdG) was measured by HPLC before and after exposure to each
      LED to determine photo-oxidative stress. RESULTS: Values < 1.00 indicate
      effective phototherapy. The ratios of TB and UB were decreased to 0.85, 0.89,
      1.07, 0.90, and 1.04, and 0.85, 0.94, 0.93, 0.89, and 1.09 after exposure to
      blue, filtered blue, FB50, and filtered blue mixed with green LED, respectively.
      In contrast, urinary 8-OHdG increased to 2.03, 1.25, 0.96, 1.36, 1.31, and 1.23
      after exposure to blue, filtered blue, FB50, mixed, green LED, and control,
      indicating side-effects (> 1.00), respectively. CONCLUSIONS: Blue plus green
      phototherapy is as effective as blue phototherapy and it attenuates irradiation
      induced oxidative stress. PRACTICE IMPLICATIONS: Combined blue and green spectra
      might be effective against neonatal hyperbilirubinemia.

PMID- 25984652
TI  - Circulating microRNAs are promising novel biomarkers for drug-resistant epilepsy.
AB  - MicroRNAs (miRNAs) open up a new field for molecular diagnosis for cancer and
      other diseases based on their stability in serum. However, the role of
      circulating miRNAs in plasma/serum in epilepsy diagnosis is still unclear. The
      aim of this study was to evaluate whether miRNAs can be used as biomarkers for
      drug-resistant epilepsy. We measured the differences in serum miRNA levels
      between 30 drug-resistant patients and 30 drug-responsive epilepsy patients in
      discovery and training phases using Illumina HiSeq2000 sequencing followed by
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays.
      The selected miRNAs were then validated in 77 drug-resistant epilepsy patients,
      81 drug-responsive epilepsy patients and 85 healthy controls by qRT-PCR. We found
      that circulating miRNAs are differentially expressed between drug-resistant group
      and drug-responsive group. MiR-194-5p, -301a-3p, -30b-5p, -342-5p and -4446-3p
      were significantly deregulated in drug-resistant group compared to drug
      responsive group and control group. Among these 5 miRNAs, miR-301a-3p had the
      best diagnostic value for drug-resistant epilepsy with 80.5% sensitivity and
      81.2% specificity, and was negatively associated with seizure severity. These
      provide the rationale for further confirmation studies in larger prospective
      cohorts and in other ethnics. 

PMID- 25984654
TI  - Effect of delayed cord clamping (DCC) on breathing and transition at birth in
      very preterm infants.
AB  - BACKGROUND: The effects of delayed cord clamping (DCC) on transition in preterm
      infants are important as this procedure is becoming increasingly recommended. The
      aim of this study was to compare the effects of DCC with an historical cohort.
      METHOD: In this observational study, outcomes for infants <= 29 weeks were
      compared with a group born before the introduction of DCC. The intended
      intervention was DCC for 40s. Primary outcomes were the need for resuscitation
      and intubation in infants undergoing DCC, whilst taking note of their breathing
      during the procedure. Neonatal morbidities were analysed, including the
      association between breathing during DCC and outcome. RESULTS: There were 62
      infants in the DCC group, and 62 who received immediate cord clamping (ICC).
      Maternal and infant characteristics including gestational age (p = 0.76) and
      birth weight (p = 0.74) between groups were not significantly different. 70% of
      the DCC group breathed regularly at birth. Comparing the DCC and ICC groups,
      there was no significant difference in 1 min and 5 min Apgar scores or in the
      number requiring intubation at birth (p = 0.88). Likewise, admission temperatures
      were similar (p = 0.57). There was a significant increase in the rate of chronic
      lung disease in the DCC group (p = 0.013). When comparing the infants who
      breathed during DCC with the non-breathers; the non-breathing group was more
      likely to be intubated (p = 0.01), have chronic lung disease (p = 0.02), and
      severe intraventricular haemorrhage (p = 0.02). CONCLUSION: DCC in these very
      preterm infants was well tolerated and the majority established spontaneous
      respiration whilst DCC was occurring. Infants who did not breathe during DCC had
      worse outcomes.

PMID- 25984655
TI  - Second to fourth digit ratio (2D:4D) and coronary heart disease.
AB  - INTRODUCTION: Sex steroid exposure during human development may influence disease
      susceptibility. Second to fourth digit ratio (2D:4D) is thought to be a putative
      biomarker for prenatal hormone level during foetal life. Recently there has been
      a great deal of interest in 2D:4D and risk of disease in adulthood. METHODS: We
      explored the relationship between 2D:4D ratio and coronary heart disease.
      Photocopies of the two hands of 310 males (controls: 155; patients: 155) were
      collected at Yin chuan city, in the Ningxia province of China. Left hand, right
      hand, mean hand and right minus left 2D:4D (Dr-l) were analysed. RESULTS: The
      mean values of 2D:4D ratio in patients were higher than those of CSIN controls.
      The patients showed significantly higher 2D:4D (left hand: P < 0.01; right hand,
      mean hand: P < 0.05) than controls. In patients, 2D:4D (especially left hand
      2D:4D) were inversely associated with age at diagnosis (left hand: P < 0.001;
      right hand, mean hand: P < 0.05). No association between Dr-l and age or age at
      presentation of disease was observed in the groups. CONCLUSION: 2D:4D may
      correlate particularly with risk of coronary heart disease in Chinese men.

PMID- 25984656
TI  - A Brief, Intensive Application of Multi-Family-Based Treatment for Eating
      Disorders.
AB  - There is a continued need to improve upon the efficacy and availability of
      treatments for anorexia nervosa. Family-based therapy for anorexia nervosa
      demonstrates strong empirical evidence; however, trained treatment providers are
      limited and a subsample of participants receiving the treatment fail to respond.
      The intensive family treatment program is a brief, time-limited, multi-family
      program that trains families of adolescents with eating disorders to oversee
      their adolescents' recovery at home by providing psychoeducation, skills
      training, and immersive practice over the course of a 5-day period. This article
      provide a description of the program by summarizing underlying theoretical
      principles and key therapeutic components. 

PMID- 25984657
TI  - FFLO order in ultra-cold atoms in three-dimensional optical lattices.
AB  - We investigate different ground-state phases of attractive spin-imbalanced
      populations of fermions in three-dimensional optical lattices. Detailed numerical
      calculations are performed using Hartree-Fock-Bogoliubov theory to determine the
      ground-state properties systematically for different values of density, spin
      polarization and interaction strength. We first consider the high density and low
      polarization regime, in which the effect of the optical lattice is most evident.
      We then proceed to the low density and high polarization regime where the effects
      of the underlying lattice are less significant and the system begins to resemble
      a continuum Fermi gas. We explore the effects of density, polarization and
      interaction on the character of the phases in each regime and highlight the
      qualitative differences between the two regimes. In the high-density regime, the
      order is found to be of Larkin-Ovchinnikov type, linearly oriented with one
      characteristic wave vector but varying in its direction with the parameters. At
      lower densities the order parameter develops more structures involving multiple
      wave vectors. 

PMID- 25984658
TI  - 2-Bromoethanesulfonate degradation in bioelectrochemical systems.
AB  - 2-Bromoethanesulfonate (BES) is the most reported chemical inhibitor for
      methanogenesis in laboratory-scale bioelectrochemical systems. However, there is
      doubt about BES's long-term effectiveness in microbial fuel cells (MFCs). We
      observed BES degradation in MFCs, whereas not in microbial electrolysis cells
      (MECs). Our results suggest that BES degradation is only possible under aerobic
      conditions (such as in MFCs) when some oxygen diffuses through the cathode.
      Experimental BES degradation was linked to the release of bromide (Br(-)) into
      the medium, with an average recovery of 67 +/- 16%. Microbial analysis of the
      cathodic biomass distribution revealed the presence of Pseudomonas and
      Alcaligenes genera, which are able to use sulfonates as carbon or sulfur sources
      under aerobic conditions.

PMID- 25984659
TI  - Electrochemical evaluation of poly(3,4-ethylenedioxythiophene) films doped with
      bacteria based on viability analysis.
AB  - To immobilize viable bacteria on an electrode, we present a novel and
      straightforward technique that relies on the negative zeta-potentials of bacteria
      for insertion into conducting polymers as dopants. In the present study, we
      conducted an electrochemical polymerization of poly(3,4-ethylenedioxythiophene)
      (PEDOT) doped with various gram-negative bacteria, including Pseudomonas
      aeruginosa, Escherichia coli, and Shewanella oneidensis. The PEDOT film doped
      with bacteria indicated a typical redox response, high conductivity, and
      electrochemical stability. Fluorescence microscopy confirmed that approximately
      90% of the bacteria incorporated into the PEDOT film at >0.5 MUm in thickness
      were viable.

PMID- 25984660
TI  - Autoimmune myelofibrosis and systemic lupus erythematosus in a middle-aged male
      presenting only with severe anemia: a case report.
AB  - Autoimmune myelofibrosis is a distinct clinicopathologic entity that occasionally
      occurs with autoimmune disorders such as systemic lupus erythematosus (SLE) and
      rheumatoid arthritis. Most cases of autoimmune myelofibrosis have been reported
      in female patients with a known history of SLE. We report a case of a middle-aged
      male patient with an unusual presentation of SLE and autoimmune myelofibrosis who
      presented only with severe anemia initially and was later diagnosed with SLE and
      autoimmune myelofibrosis. The patient's condition improved dramatically after
      treatment with corticosteroids.SLE and autoimmune myelofibrosis is a rare but
      potentially devastating condition. Anemia maybe the only presenting symptom in
      addition to bone marrow fibrosis and careful clinical and laboratory assessment
      is imperative. Corticosteroids maybe useful and spare patients from bone marrow
      transplantation.

PMID- 25984661
TI  - Preoperative serum CA125 levels predict the prognosis in hyperbilirubinemia
      patients with resectable pancreatic ductal adenocarcinoma.
AB  - Serum carbohydrate antigen 19-9 (CA19-9) is widely used to predict the prognosis
      for pancreatic ductal adenocarcinoma (PDAC). However, hyperbilirubinemia and the
      CA19-9 nonsecretor phenotype restrict the usage of serum CA19-9 alone. The goal
      of this study was to confirm the prognostic role of preoperative serum CA125 in
      PDAC, especially in patients with jaundice.A total of 211 patients with resected
      PDAC were eligible for this retrospective study, and were classified into 2
      groups based on serum bilirubin levels. The prognostic significance of all
      clinicopathologic factors was evaluated by univariate and multivariate analyses,
      and the performance of each factor in predicting overall survival (OS) and
      recurrence-free survival (RFS) was compared.High preoperative CA125, high TNM
      stage, and lymph node metastasis were independent risk predictors for OS and RFS
      in all patients and the 2 subgroups, but high CA19-9 was only significant when
      considering all patients and those with nonelevated bilirubin. Using time
      dependent receiver-operating characteristic analysis, better predictive
      performance for OS and RFS was observed for serum CA19-9 as compared to serum
      CA125 in these patients.High serum CA125 can independently predict poor
      prognosis. Importantly, in PDAC patients with hyperbilirubinemia, preoperative
      serum CA125 can predict the prognosis, whereas CA19-9 cannot. Preoperative CA19-9
      had better predictive performance for survival than CA125, and the performance of
      CA19-9 did not decline between all patients and those with nonelevated bilirubin,
      but was significantly affected by hyperbilirubinemia.

PMID- 25984662
TI  - Neurokinin-1 receptor antagonists in preventing postoperative nausea and
      vomiting: a systematic review and meta-analysis.
AB  - Newly developed neurokinin-1 receptor (NK-1R) antagonists have been recently
      tried in the prevention of postoperative nausea and vomiting (PONV). This
      systematic review and meta-analysis was conducted to explore whether NK-1R
      antagonists were effective in preventing PONV.The PRISMA statement guidelines
      were followed. Randomized clinical trials (RCTs) that tested the preventive
      effects of NK-1R antagonists on PONV were identified by searching EMBASE, CINAHL,
      PubMed, and the Cochrane Library databases followed by screening. Data extraction
      was performed using a predefined form and trial quality was assessed using a
      modified Jadad scale. The primary outcome measure was the incidence of PONV. Meta
      analysis was performed for studies using similar interventions. Network meta
      analysis (NMA) was conducted to compare the anti-vomiting effects of placebo,
      ondansetron, and aprepitant at different doses.Fourteen RCTs were included. Meta
      analysis found that 80 mg of aprepitant could reduce the incidences of nausea (3
      RCTs with 224 patients, pooled risk ratio (RR) = 0.60, 95% confidence interval
      (CI) = 0.47 to 0.75), and vomiting (3 RCTs with 224 patients, pooled RR = 0.13,
      95% CI = 0.04 to 0.37) compared with placebo. Neither 40 mg (3 RCTs with 1171
      patients, RR = 0.47, 95% CI = 0.37 to 0.60) nor 125 mg (2 RCTs with 1058
      patients, RR = 0.32, 95% CI = 0.13 to 0.78) of aprepitant showed superiority over
      4 mg of ondansetron in preventing postoperative vomiting. NMA did not find a dose
      dependent effect of aprepitant on preventing postoperative vomiting.Limited data
      suggested that NK-1R antagonists, especially aprepitant were effective in
      preventing PONV compared with placebo. More large-sampled high-quality RCTs are
      needed.

PMID- 25984663
TI  - Cognitive severity-specific neuronal degenerative network in charcoal burning
      suicide-related carbon monoxide intoxication: a multimodality neuroimaging study
      in Taiwan.
AB  - While carbon monoxide (CO) intoxication often triggers multiple intraneuronal
      immune- or inflammatory-related cascades, it is not known whether the
      pathological processes within the affected regions evolve equally in the long
      term. To understand the neurodegenerative networks, we examined 49 patients with
      a clinical diagnosis of CO intoxication related to charcoal burning suicide at
      the chronic stage and compared them with 15 age- and sex-matched controls.
      Reconstructions of degenerative networks were performed using T1 magnetic
      resonance imaging, diffusion-tensor imaging, and fluorodeoxyglucose positron
      emission tomography (PET). Tract-specific fractional anisotropy (FA)
      quantification of 11 association fibers was performed while the clinical
      significance of the reconstructed structural or functional networks was
      determined by correlating them with the cognitive parameters. Compared with the
      controls, the patients had frontotemporal gray matter (GM) atrophy, diffuse white
      matter (WM) FA decrement, and axial diffusivity (AD) increment. The patients were
      further stratified into 3 groups based on the cognitive severities. The spatial
      extents within the frontal-insular-caudate GM as well as the prefrontal WM AD
      increment regions determined the cognitive severities among 3 groups. Meanwhile,
      the prefrontal WM FA values and PET signals also correlated significantly with
      the patient's Mini-Mental State Examination score. Frontal hypometabolic patterns
      in PET analysis, even after adjusted for GM volume, were highly coherent to the
      GM atrophic regions, suggesting structural basis of functional alterations. Among
      the calculated major association bundles, only the anterior thalamic radiation FA
      values correlated significantly with all chosen cognitive scores. Our findings
      suggest that fronto-insular-caudate areas represent target degenerative network
      in CO intoxication. The topography that occurred at a cognitive severity-specific
      level at the chronic phase suggested the clinical roles of frontal areas.
      Although changes in FA are also diffusely distributed, different regional changes
      in AD suggested unequal long-term compensatory capacities among WM bundles. As
      such, the affected WM regions showing irreversible changes may exert adverse
      impacts to the interconnected GM structures.

PMID- 25984664
TI  - Interest of ultrasonographic assessment of diaphragmatic function in cardiac
      rehabilitation center: a case report.
AB  - Diaphragmatic paresis is a rare but recognized complication of atrial
      fibrillation ablation.A 59-year-old woman experiencing dyspnea in supine position
      and for minimal effort was admitted in a cardiac rehabilitation center. One month
      before, she was referred to a cardiac center to ablation of paroxysmal atrial
      fibrillation. After the procedure, the patient developed respiratory failure
      attributed to aspiration pneumonia and requiring mechanical ventilation.At
      admission in the rehabilitation center, M-mode ultrasonography reported an
      absence of movement of the right hemidiaphragm during quiet breathing and a
      paradoxical movement during voluntary sniffing.Chest ultrasonography can be
      useful to detect diaphragmatic dysfunction in patients suffering from dyspnea, at
      admission in a cardiac rehabilitation center. Its use should be envisaged more
      frequently.

PMID- 25984665
TI  - Prevalence and risk factors of acute lower gastrointestinal bleeding in Crohn
      disease.
AB  - Acute lower gastrointestinal bleeding (ALGIB) is a rare but potentially life
      threatening complication of Crohn disease (CD). Thus far, few studies of ALGIB in
      the context of CD have been published, most of which were case reports with
      limited value. We aimed to explore the prevalence of ALGIB in CD patients,
      evaluate risk factors for hemorrhagic CD and its recurrence, and analyze clinical
      data of the death cases.A total of 1374 CD patients registered from January 2007
      to June 2013 were examined. Medical records of 73 patients with ALGIB and 146
      matched as controls were reviewed and analyzed retrospectively. Logistic
      regression and Cox proportional hazards analyses were performed to identify risk
      factors for ALGIB and the cumulative probability of rebleeding. Kaplan-Meier
      curves with log-rank tests were used to demonstrate the cumulative survival rates
      of rebleeding.The prevalence of ALGIB was 5.31% (73/1374) in this study. In the
      univariate analysis, possible risk factors for ALGIB were duration of CD (odds
      ratio [OR] 0.60, 95% confidence interval [CI] 0.33-1.09, P = 0.095), perianal
      disease (OR 1.96, 95% CI 0.92-4.20, P = 0.082), left colon involvement (OR 2.16,
      95% CI 1.10-4.24, P = 0.025), azathioprine use >=1 year (OR 0.46, 95% CI 0.23
      0.90, P = 0.023), and previous hemorrhage history (OR 11.86, 95% CI 5.38-26.12, P
      < 0.0001). In the multivariate analysis, left colon involvement (OR 2.26, 95% CI
      1.04-4.91, P = 0.039), azathioprine use >=1 year (OR 0.44, 95% CI 0.20-0.99, P =
      0.044), and previous hemorrhage history (OR 13.04, 95% CI 5.66-30.04, P < 0.0001)
      remained independent influencing factors. Older age (HR 0.23, 95% CI 0.07-0.77, P
      = 0.018), surgical treatment (HR 0.17, 95% CI 0.06-0.50, P < 0.001), and having
      bleeding episodes >3 months ago (HR 0.24, 95% CI 0.07-0.82, P = 0.022) resulted
      to be predictors associated with rebleeding after discharge. Patients who died
      often suffered severe concomitant diseases, and the overall mortality rate was
      8.22% (6/73).We speculated that a special hemorrhagic phenotype of CD that was
      predisposed to rebleeding may exist. Further studies are warranted to investigate
      the pathogenesis and discover the optimum treatments of choice.

PMID- 25984666
TI  - Fine-needle aspirate CYFRA 21-1, an innovative new marker for diagnosis of
      axillary lymph node metastasis in breast cancer patients.
AB  - To compare the value of cytokeratin fragment 21-1 (CYFRA 21-1) concentration in
      the fine-needle biopsy aspirates (fine needle aspirate [FNA] CYFRA 21-1) with
      cytopathology of fine-needle aspiration biopsy (FNA cytology) and to assess
      whether CYFRA 21-1 concentrations from ultrasound-guided fine-needle aspiration
      biopsy (US-FNAB) specimens (FNA CYFRA 21-1) is not inferior to FNA cytology in
      the diagnosis of axillary lymph node (ALN) metastasis of breast cancer
      patients.This study received institutional review board approval, and written
      informed consent was obtained from all patients. US-FNAB was performed in 373
      ALNs from 358 patients with invasive breast cancer. Concentrations of CYFRA 21-1
      were measured from washouts of the syringe used during US-FNAB (FNA CYFRA 21-1),
      and ALN metastasis was determined using a cutoff value of 1.93 ng/mL. FNA
      cytology, intraoperative sentinel lymph node biopsy, and surgical pathology
      results were reviewed and analyzed. The noninferiority margin for the difference
      in accuracies between FNA cytology and FNA CYFRA 21-1 was set as 5%.Among 373
      ALNs, 136 (36.5%) were benign, and 237 (63.5%) were metastatic. The mean FNA
      CYFRA 21-1 was significantly higher in metastatic ALNs compared to that in benign
      ALNs (P = 0.001). For the diagnosis of ALN metastasis, the sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of FNA CYFRA 21-1 (cutoff value 1.93 ng/mL) were not significantly different from
      those of FNA cytology (P > 0.05). FNA CYFRA 21-1 reached statistical
      noninferiority to FNA cytology in terms of diagnostic accuracy for ALN
      metastasis. Of the 20 ALNs (8 metastasis, 12 benign) that showed insufficient
      results on FNA cytology, FNA CYFRA 21-1 accurately diagnosed 15 ALNs (4
      metastasis, 11 benign).The diagnostic performance of FNA CYFRA 21-1 is comparable
      with that of FNA cytology for breast cancer ALN metastasis. Our results indicate
      that FNA CYFRA 21-1, using an US-FNAB specimen, can be a useful method equal to
      FNA cytology in terms of diagnostic accuracy.

PMID- 25984667
TI  - An elevated percentage of reticulated platelet is associated with increased
      mortality in septic shock patients.
AB  - Microcirculatory changes and coagulation disturbances are thought to play a key
      role in sepsis. Some evidence suggests that the percentage of reticulated
      platelets (RP%) may be a valuable and cost-effective sepsis screening parameter.
      This was a prospective study in surgical patients to investigate the potential
      value of RP% as a predictor of mortality in septic shock patients.This was a
      prospective study conducted in a surgical critical care center of a Chinese
      tertiary care hospital. Consecutive septic shock patients were enrolled at
      admission. Age- and sex-matched non-septic patients were recruited as control
      patients. RP% was determined by flow cytometry in 68 septic shock patients and 68
      controls.Compared with survivors, septic patients who died presented with a
      significantly higher RP% (P < 0.001). The area under the receiver-operating
      characteristic curve for the RP% association with mortality was 0.867 (95 % CI
      0.780-0.953, P < 0.001). Kaplan-Meier survival curves showed that mortality risk
      was significantly different when patients were stratified based on RP% (P <
      0.001). This association was preserved in a multi-logistic regression analysis
      that included clinical confounders (P < 0.014).This prospective study
      demonstrates that increased RP% identifies septic shock patients who have a high
      risk of death. RP% has the potential to act as a marker for patient
      stratification in future clinical trials.

PMID- 25984668
TI  - Hepatic angiosarcoma may have fair survival nowadays.
AB  - Hepatic angiosarcoma (HAS) is rare but often fatal. A review of literature in
      1979 found that only 3% of the 70 patients lived for more than 2 years, but the
      survival might have been improved over the years. We conducted a retrospective
      study and reviewed the medical records of patients who visited a teaching
      hospital in Taiwan from January 2000 to August 2010 and had pathological proof of
      HAS. In addition, we conducted a review of literature and compared those who
      survived for 2 years or more to those who did not. Of the 3503 patients with
      primary liver cancer we identified, 9 had HAS, of whom 3 (33.3%) survived for 2
      years or more. One survived for 24 months without surgical resection, and the
      other two received surgery with postoperative chemotherapy and were still alive
      32 and 37 months later, respectively. Through reviewing literature, we identified
      3 more patients in Taiwan who had survived for 2 years or more. One survived for
      42 months without surgical resection, the other two received segmentectomy with
      postoperative chemotherapy or radiotherapy. We also identified 8 such cases
      outside Taiwan, including 1 who received chemotherapy without surgery and
      survived for 53 months. None of the differences in the clinical characteristics
      between those who had and had not survived for 2 years or more reached
      statistical significance. In conclusion, we believe the combination of surgery
      and adjuvant chemotherapy may be able to achieve long-term survival in some HAS
      patients nowadays, and it is even possible to achieve fair survival using
      chemotherapy alone.

PMID- 25984669
TI  - Serum Cyr61 is associated with clinical disease activity and inflammation in
      patients with systemic lupus erythematosus.
AB  - Our previous studies have shown that secreted extracellular matrix-associated
      protein Cysteine rich angiogenic inducer 61 (Cyr61), a novel proinflammatory
      factor, is involved in the pathogenesis of rheumatoid arthritis (RA). However,
      whether Cyr61 has any effect in systemic lupus erythematosus (SLE) remains
      unknown. This study aims to assess the level of serum Cyr61 and to investigate
      the association of serum Cyr61 and clinical disease activity in SLE. We found the
      level of serum Cyr61 in patients with SLE was significantly higher than healthy
      controls (P < 0.001), and Cyr61 was high expressed in renal tubule of lupus
      nephritis compared to control. The sensitivity of Cyr61 in diagnosis of SLE was
      47.3%. In receiver operating characteristic (ROC) curve analysis, the area under
      the curve (AUC) was 0.830, with a 95% confidence interval (CI) from 0.776 to
      0.885. Cyr61 was present in 60.0%, 54.5%, and 41.5% of anti-double stranded DNA
      (dsDNA), anti-antinuclear antibodies (ANA), and anti-Sm negative SLE patients,
      respectively. Serum Cyr61 levels were significantly higher in high systemic lupus
      erythematosus disease activity index (SLEDAI) group than that in low SLEDAI group
      (P = 0.003). Correlation analyzes showed a significant negative correlation
      between serum Cyr61 and complements (C3) (P = 0.015), C4 (P = 0.04). Moreover,
      increased Cyr61 level in SLE was associated with serum level of TNF-alpha,
      interleukin 6 (IL-6), and IL-17. In conclusion, serum Cyr61 was increased in
      patients with SLE which was associated with clinical disease activity and
      inflammation in SLE, suggesting Cyr61 may be a novel potential auxiliary marker
      for the diagnosis of SLE.

PMID- 25984670
TI  - Factors predicting abnormal liver function tests induced by Graves' disease
      alone: a retrospective cohort study.
AB  - Abnormal liver function tests (LFTs) are often observed in patients with Graves'
      disease (GD). To date, there are limited data demonstrating the factors or
      biochemical indexes contributing to LFT abnormalities in this patient population.
      The aim of this study was to explore factors predicting abnormal LFTs induced by
      GD alone. This was a retrospective study of 289 consecutive cases of newly
      diagnosed and untreated patients with GD. All patients were divided into abnormal
      LFTs (group A) and normal LFTs (group B). In total, 205 (70.9%) cases were found
      to have at least 1 LFT abnormality. Among them, the frequencies of ALT, AST, ALP,
      gamma-GTP, TBIL and DBIL abnormalities were 52.7%, 32.2%, 45.9%, 38.5%, 23.4%,
      2.9%, respectively, and the number of patients with 1 to 6 hepatic variable
      abnormalities were 89, 64, 30, 16, 6 and 0, respectively. Logistic regression
      analysis was used to determine predictive factors contributing to abnormal LFTs.
      A receiver operating characteristic (ROC) curve was also plotted to verify the
      accuracy of predictors. In the univariate analysis, patients in group A had
      significantly higher FT3 concentration (37.5 vs 33.4 pmol/L, P = 0.009), FT4
      concentration (85.7 vs 77.4 pmol/L, P = 0.002) and TRAb level (22.2 vs 17.4 IU/L,
      P < 0.001) when compared with those in group B. Binary logistic regression
      analysis identified higher FT4 concentration (odds ratio [OR]: 1.017, 95%
      confidence interval [CI]: 1.005-1.030, P = 0.006) and higher TRAb value (OR:
      1.038, 95% CI:1.013-1.064, P = 0.003) to be independent risk factors predicting
      abnormal LFTs. The optimal cutoffs for FT4 and TRAb to predict abnormal LFTs were
      75 pmol/L and 15 IU/L, respectively, based on ROC analysis.

PMID- 25984671
TI  - Increased levels of systolic blood pressure within the normal range are
      associated with significantly elevated risks of nonalcoholic fatty liver disease.
AB  - A positive association between hypertension or high-normal blood pressure (BP)
      and risk of nonalcoholic fatty liver disease (NAFLD) is well-known; however, no
      data have been generated exploring the risk of NAFLD within the normal range of
      BP. We aimed to assess the association between normal systolic blood pressure
      (SBP) and risk of NAFLD.A total of 27,769 subjects from 2 separate medical
      centers were included. Subjects were divided into 4 groups (G1 to G4) by SBP
      levels: G1: 90-99 mmHg, G2: 100-109 mmHg, G3: 110-119 mmHg, and G4: 120-129 mmHg.
      The prevalence, hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD
      were calculated across each group, using the G1 as reference.Higher SBP was
      observed in subjects with NAFLD than those without NAFLD. The prevalence of NAFLD
      in a cross-sectional population from G1 to G4 was 6.1%, 13.6%, 19.6%, and 25.8%,
      respectively. The HRs for NAFLD in the longitudinal population were 2.17 (95% CI
      1.60-2.93), 3.87 (95% CI 2.89-5.16), 5.81 (95% CI 4.32-7.81) for G2, G3, and G4,
      respectively. After adjusting for known confounding variables, HRs of G2 to G4
      were 1.44 (95% CI 1.06-1.96), 1.94 (95% CI 1.44-2.61), 2.38 (95% CI 1.75-3.23),
      respectively.This is the first study to demonstrate that increased levels of SBP
      within the normal range are associated with significantly elevated risks of
      NAFLD, independent of other confounding factors.

PMID- 25984672
TI  - Efficacy of coblation annuloplasty in discogenic low back pain: a prospective
      observational study.
AB  - In degenerative disc, the innervated outer annulus is confirmed to the major
      origin resulted in discogenic pain. To alleviate the discogenic pain,
      annuloplasty with electrothermal technology was proved to be effective, which
      mainly involves the thermal heating of the annulus to denature collagen fibers
      and denervate posterior annular nerve fibers. However, little is known that
      efficacy of annuloplasty with coblation technology in treating discogenic pain
      through directly interrupting nerves in outer annulus.The purpose of this study
      was to evaluate the clinical outcomes of coblation annuloplasty for the treatment
      of discogenic low back pain.In a clinical prospective observational study, 17
      consecutive patients with discogenic low back pain underwent coblation
      annuloplasty under local anesthesia. Pain visual analogue scale (VAS) scores,
      patient responses stating significant (>=50%) pain relief, and modified MacNab
      criteria were adopted to evaluate the pain intensity, degree of pain relief, and
      functional status after 6 months of follow-up.The preoperative pain VAS score was
      6.5 +/- 0.8(95% confidence interval [CI] 6.1-6.9) and the pain VAS score
      decreased to 2.9 +/- 1.6 (95% CI 2.1-3.8), 2.9 +/- 1.7 (95% CI 2.1-3.8), 3.2 +/-
      1.6 (95% CI 2.4-4.1), 3.2 +/- 1.7 (95% CI 2.4-4.2) at 1 week and 1, 3 and 6 month
      postoperatively, respectively. 12 (70.6%), 11 (64.7%), 10 (58.8%) and 10 (58.8%)
      of patients reported significant pain relief at 1 week and 1, 3 and 6 months
      postoperatively. At 1, 3, and 6 months postoperatively, the numbers of patients
      with "excellent" or "good" ratings were 13 (76.5%), 11 (64.7%), and 10 (58.8%)
      according to the modified MacNab criteria. No serious complications were
      observed.The finds show that coblation annuloplasty is an effective, safe, and
      less uncomfortable procedure in managing discogenic low back pain.

PMID- 25984673
TI  - Successful treatment of multifoci nocardial brain abscesses: a case report and
      literature review.
AB  - Brain nocardiosis is a serious opportunistic infection with high mortality. It
      exists more common in the immunocompromised hosts than the immunocompetent
      patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) has been mostly considered as
      the choice of the medical treatment. Linezolid is also newly found to be
      effective to avoid the invasive surgery. The authors reported a case of patient
      with multifoci nocardial brain abscesses who failed with the combination of
      linezolid and TMP-SMZ alone but recovered with the surgery intervention and
      sequential antibiotics for 2 years. The patient lived a high quality life without
      recurrence and complications during the 30 months follow-up.Through the
      literature review, we recommend earlier stereotactic aspiration for diagnosis,
      combination with surgery intervention and prolonged anti-infection therapy would
      improve the prognosis.

PMID- 25984674
TI  - Amiodarone use is associated with increased risk of stroke in patients with
      nonvalvular atrial fibrillation: a nationwide population-based cohort study.
AB  - Atrial fibrillation (AF), the most common sustained arrhythmia requiring
      treatment worldwide, is one of the major causes of ischemic stroke. Although
      amiodarone is commonly used for rhythm control in AF, its relationship with
      stroke has rarely been addressed.We evaluated 16,091 patients who were diagnosed
      with AF (Classification of Diseases, 9th Revision, Clinical Modification [ICD-9
      CM] 427.31 and 427.32) between 1998 and 2011; the date of AF diagnosis was set as
      the index date. Patients with a history of stroke (ICD-9-CM 430-438) who received
      amiodarone before the index date or during the following 30 days, or who
      experienced stroke within 30 days of receiving amiodarone were excluded. Finally,
      7548 patients with AF were included in this study and divided into 2 groups
      according to whether they received amiodarone (Anatomical Therapeutic Chemical
      code C01BD01) during the study period.The risk of ischemic stroke in AF patients
      receiving amiodarone was 1.81-fold (95% confidence interval [CI] 1.52-2.16), 1.79
      fold (95% CI 1.50-2.14), and 1.78-fold (95% CI 1.49-2.13) higher than in those
      who did not receive amiodarone, according to crude, Model 1, and Model 2 Cox
      proportional hazard regression models, respectively. In a demographically
      stratified analysis, the risk of ischemic stroke was significantly higher in
      patients aged <65 years, with no comorbidities, who were also taking digoxin or
      had a low CHA2DS2VASc score.Amiodarone treatment is associated with an increased
      risk of stroke in patients with AF, especially in those who have an initial low
      risk of stroke. Antiplatelet drugs and warfarin could reduce the stroke risk in
      AF patients receiving amiodarone. However, as the combination of digoxin and
      amiodarone increases the risk of stroke in these patients, the combination of
      these 2 drugs should be avoided.

PMID- 25984675
TI  - Vitamin D plasma levels and in-hospital and 1-year outcomes in acute coronary
      syndromes: a prospective study.
AB  - Deficiency in 25-hydroxyvitamin D (25[OH]D), the main circulating form of vitamin
      D in blood, could be involved in the pathogenesis of acute coronary syndromes
      (ACS). To date, however, the possible prognostic relevance of 25 (OH)D deficiency
      in ACS patients remains poorly defined. The purpose of this prospective study was
      to assess the association between 25 (OH)D levels, at hospital admission, with in
      hospital and 1-year morbidity and mortality in an unselected cohort of ACS
      patients.We measured 25 (OH)D in 814 ACS patients at hospital presentation.
      Vitamin D serum levels >30 ng/mL were considered as normal; levels between 29 and
      21 ng/mL were classified as insufficiency, and levels < 20 ng/mL as deficiency.
      In-hospital and 1-year outcomes were evaluated according to 25 (OH)D level
      quartiles, using the lowest quartile as a reference.Ninety-three (11%) patients
      had normal 25 (OH)D levels, whereas 155 (19%) and 566 (70%) had vitamin D
      insufficiency and deficiency, respectively. The median 25 (OH)D level was similar
      in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial
      infarction (NSTEMI) patients (14.1 [IQR 9.0-21.9] ng/mL and 14.05 [IQR 9.1-22.05]
      ng/mL, respectively; P = .88). The lowest quartile of 25 (OH)D was associated
      with a higher risk for several in-hospital complications, including mortality. At
      a median follow-up of 366 (IQR 364-379) days, the lowest quartile of 25 (OH)D,
      after adjustment for the main confounding factors, remained significantly
      associated to 1-year mortality (P < .01). Similar results were obtained when
      STEMI and NSTEMI patients were considered separately.In ACS patients, severe
      vitamin D deficiency is independently associated with poor in-hospital and 1-year
      outcomes. Whether low vitamin D levels represent a risk marker or a risk factor
      in ACS remains to be elucidated.

PMID- 25984676
TI  - Increased risk of Parkinson disease in patients with carbon monoxide
      intoxication: a population-based cohort study.
AB  - The present study evaluated the association of carbon monoxide intoxication (COI)
      with Parkinson disease (PD).A total of 9012 adults newly diagnosed with COI were
      enrolled in this study as the COI cohort. The control (non-COI) cohort,
      comprising 36,048 participants, was matched for each COI patient according to
      age, sex, and the year of hospitalization. We calculated the hazard ratios (HR)
      and 95% confidence intervals by using a Cox proportional hazards regression
      model.The overall incidence of PD (per 10,000 person-year) in the COI and non-COI
      cohorts was 27.4 and 2.53, respectively. After adjustment for age, sex, and
      comorbidities, the COI patients exhibited a 9.08-fold increased risk for PD. The
      COI patients without comorbidity exhibited a significantly higher risk of PD
      (adjusted HR = 15.8) than did the COI patients without comorbidity (adjusted HR =
      4.15). Patients with COI and receiving hyperbaric oxygen therapy exhibited a 14.3
      fold increased risk of PD; the adjusted HR of patients who did not receive
      hyperbaric oxygen treatment was increased 7.97-fold.The risk of PD increased in
      the COI patients and the significance increased in young people. COI is a crucial
      factor leading to PD.

PMID- 25984677
TI  - Increased risk of peripheral arterial disease after hip replacement: an 11-year
      retrospective population-based cohort study.
AB  - The correlation between hip replacement (Hip-Rep) and peripheral arterial disease
      (PAD) remains uncertain. Thus, we investigated the relationship between Hip-Rep
      and risk of developing PAD in a nationwide retrospective cohort study.National
      Health Insurance data were used to assemble a cohort of patients who were
      diagnosed from 2000 to 2011. Patients with a history of PAD were excluded. A
      total of 5284 patients who received a Hip-Rep and 21,124 matched controls were
      enrolled. We used Cox proportional hazards regression model to analyze the
      adjusted risk of developing PAD.The risk of developing PAD in the Hip-Rep group
      was 1.24-fold higher (95% CI = 1.05-1.48) than that in the control group. The
      adjusted risk of developing PAD increased with patient age; compared with
      patients aged 50 years or younger, the risk among those ages at least 80 years
      was 4.87-fold higher. Patients with diabetes exhibited the highest risk of
      developing PAD (HR = 1.58, 95% CI = 1.34-1.86). Compared with patients who had
      not received a Hip-Rep or reported any comorbidity, patients who received a Hip
      Rep were 2.45-fold more likely to develop PAD (95% CI = 1.54-3.89); the risk
      increased with the number of comorbidities.Hip-Reps might be independently linked
      with an increased risk of developing PAD. The impact of Hip-Reps on this risk was
      greater in women and patients ages 65 years and younger and within the first year
      of follow-up.

PMID- 25984678
TI  - Novel and novel de novo mutations in NTRK1 associated with congenital
      insensitivity to pain with anhidrosis: a case report.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare autosomal
      recessively inherited disorder. The main clinical features of the disorder
      consist of absence of reactions to noxious stimuli and inability to sweat under
      any conditions.In this case report, a 3-year-old Chinese boy diagnosed with CIPA
      presented with the core features of CIPA, including insensitivity to noxious
      stimuli, self-mutilation, inability to sweat, and developmental delay. Clinical
      and genetic analyses were conducted on the affected boy.Sequencing analysis
      revealed an inherited novel mutation, c.1635G>C, and a novel de novo mutation,
      c.2197G>A, in the NTRK1 gene. In silico studies suggested that the mutations
      described are detrimental to the function of the protein encoded by the NTRK1
      gene.The two novel mutations described here widen the genetic spectrum of CIPA,
      and this knowledge will benefit studies addressing this disease and pain medicine
      in the future.

PMID- 25984679
TI  - Newly designed break-apart and ASPL-TFE3 dual-fusion FISH assay are useful in
      diagnosing Xp11.2 translocation renal cell carcinoma and ASPL-TFE3 renal cell
      carcinoma: a STARD-compliant article.
AB  - The diagnosis of Xp11.2 translocation renal cell carcinoma (tRCC), which relies
      on morphology and immunohistochemistry (IHC), is often either missed in the
      diagnosis or misdiagnosed. To improve the accuracy of diagnosis of Xp11.2 tRCC
      and ASPL-TFE3 renal cell carcinoma (RCC), we investigated newly designed
      fluorescence in situ hybridization (FISH) probes (diagnostic accuracy
      study).Based on the genetic characteristics of Xp11.2 tRCC and the ASPL-TFE3 RCC,
      a new break-apart TFE3 FISH probe and an ASPL-TFE3 dual-fusion FISH probe were
      designed and applied to 65 patients with RCC who were <45 years old or showed
      suspicious microscopic features of Xp11.2 tRCC in our hospital. To test the
      accuracy of the probes, we further performed reverse transcriptase-polymerase
      chain reaction (PCR) on 8 cases for which frozen tissues were available.Among the
      65 cases diagnosed with RCC, TFE3 IHC was positive in 24 cases. Twenty-two cases
      were confirmed as Xp11.2 tRCC by break-apart TFE3 FISH, and 6 of these cases were
      further diagnosed as ASPL-TFE3 RCC by ASPL-TFE3 dual-fusion FISH detection.
      Importantly, reverse transcriptase-PCR showed concordant results with the results
      of FISH assay in the 8 available frozen cases.The break-apart and ASPL-TFE3 dual
      fusion FISH assay can accurately detect the translocation of the TFE3 gene and
      ASPL-TFE3 fusion gene and can thus serve as a valid complementary method for
      diagnosing Xp11.2 tRCC and ASPL-TFE3 RCC.

PMID- 25984680
TI  - Intra-aortic balloon pump may grant no benefit to improve the mortality of
      patients with acute myocardial infarction in short and long term: an updated meta
      analysis.
AB  - Intra-aortic balloon pump (IABP) has been extensively used in clinical practice
      as a circulatory-assist device. However, current literature demonstrated
      significantly varied indications for IABP application and prognosis.The objective
      of the study was to assess the potential benefits or risks of IABP treatment for
      acute myocardial infarction (AMI) complicated with or without cardiogenic
      shock.MEDLINE and EMBASE database were systematically searched until November
      2014, using the terms as follows: IABP, IABC (intra-aortic balloon
      counterpulsation), AMI, heart infarction, coronary artery disease, ischemic heart
      disease, and acute coronary syndrome. Only randomized controlled trials (RCTs)
      that compared the use of IABP or non-IABP support in AMI with or without
      cardiogenic shock were included. Two researchers performed data extraction
      independently, and at the mean time, the risk of bias among those RCTs was also
      assessed.Of 3026 citations, 17 studies (n = 3226) met the inclusion criteria.
      There is no significant difference between IABP group and control group on the
      short-term mortality (relative risk [RR], 0.90; 95% confidence interval [CI],
      0.77-1.06; P = 0.214) and long-term mortality (RR, 0.91; 95% CI, 0.79-1.04; P =
      0.155) in AMI patients with or without cardiogenic shock. These results were
      consistent when the analysis was performed on studies that only included patients
      with cardiogenic shock, both on short-term mortality (RR, 0.91; 95% CI, 0.77
      1.08; P = 0.293) and long-term mortality (RR, 0.95; 95% CI, 0.83-1.10; P =
      0.492). Similar result was also observed in AMI patients without cardiogenic
      shock. Furthermore, the risks of hemorrhage (RR, 1.49; 95% CI, 1.09-2.04; P =
      0.013) and recurrent ischemia (RR 0.54, 95% CI 0.37 to 0.79; P = 0.002) were
      significantly higher in IABP group compared with control group.We did not observe
      substantial benefit from IABP application in reducing the short- and long-term
      mortality, while it might promote the risks of hemorrhage and recurrent ischemia.
      Therefore, IABP may be not an optimal therapy in AMI with or without cardiogenic
      shock until more elaborate classification is used for selecting appropriate
      patients.

PMID- 25984681
TI  - Early diagnosis and successful treatment of Cryptococcus albidus keratitis: a
      case report and literature review.
AB  - Cryptococcus albidus keratitis is a rare and difficult diagnosed disease. Here we
      report a case of C albidus keratitis early diagnosed by dot hybridization assay
      and successfully treated with intrastromal injection of Amphotericin B (AB).A 45
      year-old man presented with left red eye for 2 days. The slit lamp examination
      exhibited deep corneal infiltrations. Smears and cultures were performed but
      revealed negative findings. Molecular detection of pathogens was performed by dot
      hybridization assay, and C albidus keratitis was diagnosed. Despite the
      identification of C albidus, the clinical condition still worsened due to deep
      corneal infiltration. After performing intrastromal injection of AB, the corneal
      infiltration gradually improved.C albidus is a rare cause of diseases in humans
      and should be considered as a potential pathogen of corneal ulcer. The prognosis
      of C albidus keratitis will improve if the condition is recognized early and
      treated properly.

PMID- 25984682
TI  - Patterns of depressive symptoms and social relating behaviors differ over time
      from other behavioral domains for young people with Down syndrome.
AB  - People with intellectual disabilities are at a higher risk for experiencing
      behavioral, emotional, and psychiatric problems in comparison with the general
      population. People with Down syndrome have been reported as experiencing fewer
      behavioral problems than others with intellectual disability, although still at a
      greater level than the non-intellectually disabled population, except for
      depression and Alzheimer disease. The aim of this study was to describe the
      trajectories of subscales of behavior, including depressive symptoms,
      communication disturbance, anxiety, disruptiveness, and social relating
      abilities, for young adults with Down syndrome.Families of young adults with Down
      syndrome living in Perth, Western Australia, participated in a questionnaire
      study over 8 years, 2004 (n = 255), 2009 (n = 191), and 2011 (n = 188).
      Questionnaires collected information about young person characteristics and
      family functioning. The parent-completed Developmental Behavior Checklist-Adult
      (DBC-A) and Developmental Behavior Checklist-Primary Carer Version (DBC-P) were
      used to measure emotional and behavioral problems. These measures include the
      following subscales: disruptive, communication and anxiety disturbances, self
      absorbed, antisocial, depressive, and social relating.DBC score declined from
      2004 to 2011 reflecting an improvement in behavior in the self-absorbed (coeff 
      0.011, 95% confidence interval (CI) -0.031, -0.008), anxiety (coef -0.009 95%CI 
      0.129, -0.006), communication disturbances (coeff -0.008, 95% CI -0.012, -0.005)
      and disruptive/antisocial behavior (coeff -0.013, 95% CI -0.016, -0.009)
      subscales. Subscales for depressive symptoms and social relating problems
      decreased less (coeff -0.003, 95% CI -0.007, -0.0001) (coeff -0.003 95% CI 
      0.007, 0.001). Young people who were lower functioning were reported as
      exhibiting significantly more behavioral problems across every subscale when
      compared with those who were higher functioning.Behavior of young adults with
      Down syndrome improves over time but depressive symptoms and social relating
      behavior problems persist into adulthood. It is possible that those with
      persistent depressive symptoms are at a high risk for developing depressive
      illness in adulthood. Identifying young people with Down syndrome who are at risk
      for developing depression in adult life has implications for prevention and early
      treatment.

PMID- 25984683
TI  - Does habituation differ in chronic low back pain subjects compared to pain-free
      controls? A cross-sectional pain rating ERP study reanalyzed with the ERFIA
      multilevel method.
AB  - The objective of the present study was to investigate cortical differences
      between chronic low back pain (CLBP) subjects and pain-free controls with respect
      to habituation and processing of stimulus intensity. The use of a novel event
      related fixed-interval areas (ERFIA) multilevel technique enables the analysis of
      event-related electroencephalogram (EEG) of the whole post stimulus range at a
      single trial level. This technique makes it possible to disentangle the cortical
      processes of habituation and stimulus intensity.In a cross-sectional study, 78
      individuals with CLBP and 85 pain-free controls underwent a rating paradigm of
      150 nonpainful and painful somatosensory electrical stimuli. For each trial, the
      entire epoch was partitioned into 20-ms ERFIAs, which acted as dependent
      variables in a multilevel analysis. The variability of each consecutive ERFIA
      period was modeled with a set of predictor variables, including 3 forms of
      habituation and stimulus intensity.Seventy-six pain-free controls and 65 CLBP
      subjects were eligible for analysis. CLBP subjects showed a significantly
      decreased linear habituation at 340 to 460 ms in the midline electrodes and C3
      (Ps < .05) and had a significantly more pronounced dishabituation for the regions
      of 400 to 460 ms and 800 to 820 ms for all electrodes, except for T3 and T4 (Ps <
      .05). No significant group differences for stimulus intensity processing were
      observed.In this study, group differences with respect to linear habituation and
      dishabituation were demonstrated. By means of the ERFIA multilevel technique,
      habituation effects were found in a broad post stimulus range and were not solely
      limited to peaks. This study suggests that habituation may be a key mechanism
      involved in the transition process to chronic pain. Future studies with a
      longitudinal design are required to solve this issue.

PMID- 25984684
TI  - Mechanisms and stereoselectivities of the Rh(I)-catalyzed carbenoid carbon
      insertion reaction of benzocyclobutenol with diazoester.
AB  - In this study, a density functional theory (DFT) study has been carried out to
      investigate the mechanisms of Rh(I)-catalyzed carbenoid carbon insertion into a C
      C bond reaction between benzocyclobutenol (R1) and diazoester (R2). The
      calculated results indicate that the reaction proceeds through five stages:
      deprotonation of R1, cleavage of the C-C bond, carbenoid carbon insertion,
      intramolecular aldol reaction, and protonation of the alkoxyl-Rh(I) intermediate.
      We have suggested and studied two possible pathways according to different
      coordination patterns (including ketone-type and enol-type coordination forms) in
      the fourth stage and found that the enol-type pathway is favorable, making the
      coordination mode of the Rh(I) center in the oxa-pi-allyl Rh(I) intermediate
      clear in this reaction system. Moreover, four possible protonation channels have
      been calculated in the fifth stage, and the computational results show that the
      H2O-assisted proton transfer channel is the most favorable. The first step of the
      third stage is rate-determining, and the first steps in stages 3 and 4 play
      important roles in determining the stereoselectivities. Moreover, the analyses of
      distortion/interaction, natural bond orbital (NBO), and molecular orbital (MO)
      have been performed to better understand this title reaction. Furthermore, the
      pathway corresponding to the RR configurational product is the most favorable
      path, which is consistent with the experimental result. This work should be
      helpful for understanding the detailed reaction mechanism and the origin of
      stereoselectivities of the title reaction and thus could provide valuable
      insights into rational design of more efficient catalysts for this type of
      reactions.

PMID- 25984685
TI  - Reply: Alternatively Activated M2 Macrophages Improve Autologous Fat Graft
      Survival in a Mouse Model through Induction of Angiogenesis.

PMID- 25984686
TI  - Flexural eczema versus atopic dermatitis.
AB  - Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory
      atopy is rarely tested for and found in these patients, systematically equating a
      flexural distribution of dermatitis with atopic dermatitis may too frequently
      result in misclassified diagnoses and potentially missed opportunity for
      intervention toward improving patients' symptoms and quality of life. We present
      a critical review of the available evidence for the atopic dermatitis diagnosis
      and discuss the similarities between atopic dermatitis and allergic contact
      dermatitis. Because neither flexural predilection nor atopy is specific for
      atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and
      propose an etymologic reclassification of atopic dermatitis to "atopy-related"
      dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like
      phenotype, and thus, flexural dermatitis cannot be assumed as atopic without
      further testing. Patch testing should at least be considered in cases of chronic
      or recurrent eczema regardless of the working diagnosis. 

PMID- 25984687
TI  - Cinnamon spice and everything not nice: many features of intraoral allergy to
      cinnamic aldehyde.
AB  - Intraoral allergic contact dermatitis (ACD) is an uncommonly reported entity. The
      most commonly implicated allergens are metals that are incorporated into dental
      appliances. Intraoral ACD to nonmetal allergens is even less frequently
      described. Cinnamic aldehyde is widely used as a flavoring agent in foods and
      dentifrices. However, intraoral ACD to cinnamon flavoring agents has only been
      sporadically reported. In these cases, a variety of sources have been implicated,
      including candy, chewing gum, mouthwash, lip sunscreen, cinnamon toast, volatile
      oils, and toothpaste. The clinical presentation of intraoral ACD reactions varies
      greatly, and as a result, clinicians often do not recognize the diagnosis.
      Furthermore, because patients are typically unable to provide a list of putative
      allergens, a high degree of clinical suspicion is required to make the correct
      diagnosis. We describe several patients with intraoral ACD caused by cinnamon and
      review the literature associated with this condition. 

PMID- 25984688
TI  - Systematic review on the efficacy, safety, and cost-effectiveness of topical
      calcineurin inhibitors in atopic dermatitis.
AB  - BACKGROUND: Topical calcineurin inhibitors (TCIs) are widely used as an
      alternative to topical corticosteroids (TCSs) in treating of atopic dermatitis,
      but their risk versus benefit compared with TCSs remains unclear. OBJECTIVE: We
      performed a systematic review of the efficacy, safety, and cost-effectiveness of
      TCI compared with TCS and emollients. METHODS: Published meta-analysis,
      systematic reviews, and individual studies from January 2005 to January 2015 on
      the comparative efficacy, safety, and cost-effectiveness of TCI against
      emollients and TCS were included. RESULTS: Tacrolimus is comparable to TCS in
      efficacy, safety profile, and cost-effectiveness. Pimecrolimus has a similar
      safety profile compared with TCS, emollients, and tacrolimus. It is superior to
      emollients but inferior to TCS and tacrolimus in efficacy and cost-effectiveness.
      The association of tacrolimus with malignancy remains uncertain. CONCLUSIONS:
      Tacrolimus is an efficacious and cost-effective alternative to TCS, but its
      benefits need to be weighed against its still uncertain risk for malignancy.
      Pimecrolimus is appropriate for mild atopic dermatitis when TCS or tacrolimus is
      unsuitable.

PMID- 25984689
TI  - Polysensitization and individual susceptibility to allergic contact dermatitis.
AB  - BACKGROUND: Patients with allergic contact dermatitis to 1 antigen have been
      shown to be at increased risk of developing delayed type hypersensitivity
      reactions to additional antigens. Both environmental and genetic factors likely
      influence the risk of sensitization. OBJECTIVE: The aim of this study was to
      determine whether polysensitization occurs at a higher frequency than would be
      expected based on chance and whether polysensitization occurs more often in
      subsets of patients with hand involvement and atopic dermatitis. METHODS: From a
      database of patch test results from a single practitioner, the probability of
      having positive reactions to 3 or more unrelated allergens was calculated under
      the assumption that positive reactions are independent and compared with the
      observed proportion having positive reactions to 3 or more unrelated allergens.
      The analysis was repeated excluding patients with leg involvement as a proxy for
      venous insufficiency dermatitis. The proportion of patients from the
      polysensitized and nonpolysensitized cohorts with either hand involvement or a
      history of atopic dermatitis was also calculated. CONCLUSIONS: Polysensitization
      occurs more often than expected based on chance. Polysensitized patients were
      more likely to have hand dermatitis. Atopic dermatitis was not significantly
      associated with polysensitization in this analysis. Polysensitized individuals
      may represent a phenotype with increased genetic susceptibility to sensitization.

PMID- 25984691
TI  - Significance of dermatologic findings in a cohort of depleted uranium-exposed
      veterans of Iraqi conflicts.
AB  - BACKGROUND: Depleted uranium (DU)-containing weapons have been used in military
      operations since 1991. There is interest in following veterans who were
      occupationally exposed to DU by either inhalation or retention of fragments. A
      cohort of DU-exposed Gulf War I veterans has been followed longitudinally at the
      Baltimore Veterans Administration Medical Center since 1993. OBJECTIVE: The aim
      was to monitor chronic dermatological findings associated with occupational DU
      exposure in the 2013 cohort. METHODS: Thirty-five veterans were evaluated. This
      study was reviewed and approved by the institutional review board and the
      Baltimore Veterans Administration Medical Center research service. Depleted
      uranium exposure was measured using creatinine-adjusted urine uranium
      concentrations (micrograms of uranium per gram of creatinine [MUgU/gCrea]).
      Detailed medical histories, physical examinations, and exposure histories were
      performed. RESULTS: Using a cutoff level of 0.1 MUgU/gCrea, 11 veterans were
      placed in the high-uranium exposure group, whereas 23 veterans were placed in the
      low-uranium exposure group. Retained fragments were documented in 91% of the high
      exposure group versus that in 13% of the low-exposure group (P < 0.001), and
      fragment-related scarring was significantly increased in the high-exposure group
      (P = 0.002). Other dermatological findings such as dermatitis were also assessed.
      CONCLUSIONS: Fragment retainment and related scarring was significantly increased
      in veterans exposed to high levels of DU. Continuous monitoring of this cohort
      will yield interesting dermatological findings related to DU exposure.

PMID- 25984690
TI  - Contact dermatitis in saffron workers: clinical profile and identification of
      contact sensitizers in a saffron-cultivating area of Kashmir Valley of North
      India.
AB  - BACKGROUND: Saffron, a bulbous perennial plant belonging to Iridaceae family, is
      the most expensive cultivated herb that is widely used for industrial and
      nonindustrial purposes. However, besides its attractive and valuable properties,
      contact dermatitis due to saffron is an uncommon reported entity. OBJECTIVES: The
      aims of this study were to determine the clinical pattern patch-testing profile
      of contact dermatitis in saffron workers and to identify the most common
      allergens/sensitizers. MATERIAL AND METHODS: One hundred ten saffron workers were
      patch-tested with 39 allergens, which included Indian standard series antigens,
      plant series antigens, and extracts from different parts of saffron flower.
      RESULTS: The allergens in Indian standard series accounted for 52.44% of positive
      reactions. Plant series and different parts of saffron accounted for 47.56% of
      the positive reactions. Among those patients with positive responses to the
      supplemental saffron allergens, 83.3% were of present or past relevance.
      CONCLUSIONS: The data observed in the present study confirm that the saffron
      dermatitis is a distinct clinical entity with characteristic clinical
      presentation and has a strong significance as an occupational allergen in those
      handling this plant. Patch testing with different parts of saffron flower has a
      role to play in finding out the etiological cause.

PMID- 25984693
TI  - A method for at-home lesional testing for fixed drug eruption.

PMID- 25984694
TI  - Allergic contact dermatitis to manganese in metallic implant.

PMID- 25984695
TI  - Occupational allergic contact dermatitis with secondary spreading from vitamin k3
      sodium bisulphite in a pig farmer.

PMID- 25984696
TI  - Set selection dynamical system neural networks with partial memories, with
      applications to Sudoku and KenKen puzzles.
AB  - After reviewing set selection and memory model dynamical system neural networks,
      we introduce a neural network model that combines set selection with partial
      memories (stored memories on subsets of states in the network). We establish that
      feasible equilibria with all states equal to +/- 1 correspond to answers to a
      particular set theoretic problem. We show that KenKen puzzles can be formulated
      as a particular case of this set theoretic problem and use the neural network
      model to solve them; in addition, we use a similar approach to solve Sudoku. We
      illustrate the approach in examples. As a heuristic experiment, we use online or
      print resources to identify the difficulty of the puzzles and compare these
      difficulties to the number of iterations used by the appropriate neural network
      solver, finding a strong relationship.

PMID- 25984698
TI  - Probing a cell-embedded megadalton protein complex by DNP-supported solid-state
      NMR.
AB  - Studying biomolecules at atomic resolution in their native environment is the
      ultimate aim of structural biology. We investigated the bacterial type IV
      secretion system core complex (T4SScc) by cellular dynamic nuclear polarization
      based solid-state nuclear magnetic resonance spectroscopy to validate a
      structural model previously generated by combining in vitro and in silico data.
      Our results indicate that T4SScc is well folded in the cellular setting,
      revealing protein regions that had been elusive when studied in vitro. 

PMID- 25984697
TI  - A microfluidic device for label-free, physical capture of circulating tumor cell
      clusters.
AB  - Cancer cells metastasize through the bloodstream either as single migratory
      circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters).
      Existing technologies for CTC enrichment are designed to isolate single CTCs, and
      although CTC clusters are detectable in some cases, their true prevalence and
      significance remain to be determined. Here we developed a microchip technology
      (the Cluster-Chip) to capture CTC clusters independently of tumor-specific
      markers from unprocessed blood. CTC clusters are isolated through specialized
      bifurcating traps under low-shear stress conditions that preserve their
      integrity, and even two-cell clusters are captured efficiently. Using the Cluster
      Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or
      prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their
      tumor origin and identified tissue-derived macrophages within the clusters.
      Efficient capture of CTC clusters will enable the detailed characterization of
      their biological properties and role in metastasis. 

PMID- 25984699
TI  - In vivo single-cell labeling by confined primed conversion.
AB  - Spatially confined green-to-red photoconversion of fluorescent proteins with high
      power, pulsed laser illumination is negligible, thus precluding optical selection
      of single cells in vivo. We report primed conversion, in which low-power, dual
      wavelength, continuous-wave illumination results in pronounced photoconversion.
      With a straightforward addition to a conventional confocal microscope, we show
      confined primed conversion in living zebrafish and reveal the complex anatomy of
      individual neurons packed between neighboring cells. 

PMID- 25984701
TI  - Decision Aids in Serious Illness: Moving What Works Into Practice.

PMID- 25984702
TI  - Analysis of chromosome damage by sister chromatid exchange (SCE) and redox
      homeostasis characterization on sheep flocks from Sardinian pasturelands.
AB  - Over the last decades, an increase of pollutants of diverse origin (industrial,
      military, mining, etc.) was recorded in several areas of Sardinia Island. We
      report the results of a multidisciplinary and complementary study based on
      cytogenetic and physiological analyses. The data obtained show the effects of the
      environmental impact on six sheep flocks (Sardinian breed) grazing on natural
      pasturelands next to possible polluted areas and compared to three herds grazing
      in different areas far from those potentially contaminated and used as control.
      Sister chromatid exchange (SCE) test was used as cytogenetic test to analyze
      chromosomal damages and it was performed on peripheral blood samples collected
      from 129 adult sheep (age > 4 years) randomly selected from polluted (92 animals)
      and control (37 animals) areas. Two types of cell cultures were performed:
      without (normal cultures) and with the addition of 5-BrdU. SCE-mean values
      estimated over 35 cells counted for each animal were 8.65 +/- 3.40, 8.10 +/-
      3.50, 8.05 +/- 3.08, 7.42 +/- 3.34, 9.28 +/- 3.56 and 8.38 +/- 3.29 in the
      exposed areas, whereas the average values were 7.86 +/- 3.31 in the control
      group. Significant increases (P < 0.01) of SCEs were found in three investigated
      areas of Southern Sardinia. Furthermore, sheep of the same flocks were
      characterized for blood redox homeostasis in order to define the potential
      targets of oxidative damage and to identify biomarkers of the extent of animal
      exposure to environmental contaminants. The plasma levels of Asc, Toc and Ret
      were found to be significantly lower (P < 0.001) in exposed sheep (I, II, IV and
      V) than in the control group. TAC as well as GPx and SOD activities were higher
      in control than in the exposed groups (P < 0.001). Finally, plasma levels of N
      Tyr, PC, and LPO were significantly lower (P < 0.001) in the control group than
      in the exposed groups.

PMID- 25984700
TI  - Combining tumor genome simulation with crowdsourcing to benchmark somatic single
      nucleotide-variant detection.
AB  - The detection of somatic mutations from cancer genome sequences is key to
      understanding the genetic basis of disease progression, patient survival and
      response to therapy. Benchmarking is needed for tool assessment and improvement
      but is complicated by a lack of gold standards, by extensive resource
      requirements and by difficulties in sharing personal genomic information. To
      resolve these issues, we launched the ICGC-TCGA DREAM Somatic Mutation Calling
      Challenge, a crowdsourced benchmark of somatic mutation detection algorithms.
      Here we report the BAMSurgeon tool for simulating cancer genomes and the results
      of 248 analyses of three in silico tumors created with it. Different algorithms
      exhibit characteristic error profiles, and, intriguingly, false positives show a
      trinucleotide profile very similar to one found in human tumors. Although the
      three simulated tumors differ in sequence contamination (deviation from normal
      cell sequence) and in subclonality, an ensemble of pipelines outperforms the best
      individual pipeline in all cases. BAMSurgeon is available at
      https://github.com/adamewing/bamsurgeon/. 

PMID- 25984703
TI  - Mercury in wintering seabirds, an aggravating factor to winter wrecks?
AB  - Every year, thousands of seabirds are cast ashore and are found dead along the
      coasts of North America and Western Europe. These massive mortality events called
      'winter wrecks' have generally been attributed to harsh climatic conditions and
      prolonged storms which affect bird energy balance and impact their body
      condition. Nevertheless, additional stress factors, such as contaminant body
      burden, could potentially cumulate to energy constraints and actively contribute
      to winter wrecks. However, the role played by these additional factors in seabird
      massive winter mortality has received little attention to date. In February/March
      2014, an unprecedented seabird wreck occurred along the Atlantic French coasts
      during which > 43,000 seabirds were found dead. By analyzing mercury (Hg)
      concentrations in various tissues collected on stranded birds, we tested the
      hypothesis that Hg played a significant role in this mortality. More
      specifically, we aimed to (1) describe Hg contamination in wintering seabirds
      found along the French coasts in 2014, and (2) determine if Hg concentrations
      measured in some vital organs such as kidney and brain reached toxicity
      thresholds that could have led to deleterious effects and to an enhanced
      mortality. We found some of the highest Hg levels ever reported in Atlantic
      puffins, common guillemots, razorbills and kittiwakes. Measured concentrations
      ranged from 0.8 to 3.6 MUg . g(-1) of dry weight in brain, 1.3 to 7.2 MUg . g(-1)
      in muscle, 2.5 to 13.5 MUg . g(-1) in kidney, 2.9 to 18.6 MUg . g(-1) in blood
      and from 3.1 to 19.5 MUg . g(-1) in liver. Hg concentrations in liver and brain
      were generally below the estimated acute toxicity levels. However, kidney
      concentrations were not different than those measured in the liver, and above
      levels associated to renal sub-lethal effects, suggesting a potential Hg
      poisoning. We concluded that although Hg was not directly responsible for the
      high observed mortality, it has been a major aggravating stress factor for
      emaciated birds already on the edge. Importantly, this study also demonstrated
      that total blood, which can be non-lethally collected in seabirds, can be used as
      a predictor of Hg contamination in other tissues.

PMID- 25984704
TI  - Emissions of PAHs derived from sugarcane burning and processing in Chiapas and
      Morelos Mexico.
AB  - Sugarcane burning is an agricultural practice implemented to ease farm worker
      duties; nevertheless, as a consequence, tons of particles are emitted to the
      atmosphere. Additionally, during harvesting the sugar-mills operate the whole day
      emitting hundreds of tons of pollutants. Therefore, health risks to neighboring
      population should be a major governmental concern, leading first to
      identification and quantification of toxic compounds, such as polycyclic aromatic
      hydrocarbons (PAHs). In order to establish the magnitude of the problem, four
      sampling campaigns of PM10 and PM2.5 were carried out in this study, during
      harvesting and no-harvesting seasons in two municipalities of Mexico, with
      different climatic and social conditions. Concentrations of PM10, PM2.5, and
      organic compounds were determined daily, followed by extraction, identification
      and quantification of the 17 EPA-established PAHs from all samples. The results
      showed that during harvest, the PM10 mass increased lightly in Chiapas, but
      approximately twice in Morelos, whereas total PAH concentrations increased twice
      and six times, respectively. The most abundant PAHs, namely: indene [1,2,3cd]
      pyrene, benzo[b]fluoranthene, benzo[a]pyrene and dibenzo [a,h] anthracene are
      composed of 5 or more aromatic rings. Of the total PAHs quantified, 44% to 52%
      corresponded to carcinogenic compounds, consequently, the overall carcinogenic
      potential increased twice or three times. Principal component analysis with
      varimax rotation was applied to source apportionment at each site, suggesting
      three different sources during harvesting: the combustion process in the sugar
      mill, sugarcane burning and vehicular emissions. The combustion markers for sugar
      mill are, BAA, BBF, BKF, BAP, IND and BGP, whereas for sugarcane burning were
      ANT, PHE, FLT and PYR. The results obtained indicate that processing and burning
      sugarcane are the main sources of the PAH levels measured, proving that the
      health risks are boosted during harvesting due to increases of PM and PAHs. 

PMID- 25984705
TI  - The Recommendation for Stenting in Stable Coronary Artery Disease--Ignoring the
      Evidence, Excluding the Patient: A Teachable Moment.

PMID- 25984706
TI  - Changes in Socioeconomic, Racial/Ethnic, and Sex Disparities in Childhood Obesity
      at School Entry in the United States.

PMID- 25984707
TI  - Single-cell Migration Chip for Chemotaxis-based Microfluidic Selection of
      Heterogeneous Cell Populations.
AB  - Tumor cell migration toward and intravasation into capillaries is an early and
      key event in cancer metastasis, yet not all cancer cells are imbued with the same
      capability to do so. This heterogeneity within a tumor is a fundamental property
      of cancer. Tools to help us understand what molecular characteristics allow a
      certain subpopulation of cells to spread from the primary tumor are thus critical
      for overcoming metastasis. Conventional in vitro migration platforms treat
      populations in aggregate, which leads to a masking of intrinsic differences among
      cells. Some migration assays reported recently have single-cell resolution, but
      these platforms do not provide for selective retrieval of the distinct migrating
      and non-migrating cell populations for further analysis. Thus, to study the
      intrinsic differences in cells responsible for chemotactic heterogeneity, we
      developed a single-cell migration platform so that individual cells' migration
      behavior can be studied and the heterogeneous population sorted based upon
      chemotactic phenotype. Furthermore, after migration, the highly chemotactic and
      non-chemotactic cells were retrieved and proved viable for later molecular
      analysis of their differences. Moreover, we modified the migration channel to
      resemble lymphatic capillaries to better understand how certain cancer cells are
      able to move through geometrically confining spaces. 

PMID- 25984709
TI  - Reversible Amisulpride-induced Elevation of Creatine Kinase (CK): A Case Series
      from the German AMSP Pharmacovigilance Project.
AB  - The elevation of creatine kinase (CK) levels without neuroleptic malignant
      syndrome has been reported for several antipsychotics. We present here 4 cases
      with CK elevation induced by amisulpride, which have been registered for the
      German pharmacovigilance project, Arzneimittelsicherheit in der Psychiatrie
      (AMSP). The magnitude of the CK elevation ranged between 1, 498 IU/L and 21,018
      IU/L. All 4 patients reported myalgia. In each case CK returned to normal after
      amisulpride discontinuation. In the fourth case, fluids were administered
      intravenously in order to prevent acute renal failure. None of the cases showed
      deterioration of renal function. Finally, we present recommendations for clinical
      practice.

PMID- 25984708
TI  - The Smc5-Smc6 heterodimer associates with DNA through several independent binding
      domains.
AB  - The Smc5-6 complex is required for the maintenance of genome integrity through
      its functions in DNA repair and chromosome biogenesis. However, the specific mode
      of action of Smc5 and Smc6 in these processes remains largely unknown. We
      previously showed that individual components of the Smc5-Smc6 complex bind
      strongly to DNA as monomers, despite the absence of a canonical DNA-binding
      domain (DBD) in these proteins. How heterodimerization of Smc5-6 affects its
      binding to DNA, and which parts of the SMC molecules confer DNA-binding activity
      is not known at present. To address this knowledge gap, we characterized the
      functional domains of the Smc5-6 heterodimer and identify two DBDs in each SMC
      molecule. The first DBD is located within the SMC hinge region and its adjacent
      coiled-coil arms, while the second is found in the conserved ATPase head domain.
      These DBDs can independently recapitulate the substrate preference of the full
      length Smc5 and Smc6 proteins. We also show that heterodimerization of full
      length proteins specifically increases the affinity of the resulting complex for
      double-stranded DNA substrates. Collectively, our findings provide critical
      insights into the structural requirements for effective binding of the Smc5-6
      complex to DNA repair substrates in vitro and in live cells. 

PMID- 25984710
TI  - A new approach to develop computer-aided detection schemes of digital mammograms.
AB  - The purpose of this study is to develop a new global mammographic image feature
      analysis based computer-aided detection (CAD) scheme and evaluate its performance
      in detecting positive screening mammography examinations. A dataset that includes
      images acquired from 1896 full-field digital mammography (FFDM) screening
      examinations was used in this study. Among them, 812 cases were positive for
      cancer and 1084 were negative or benign. After segmenting the breast area, a
      computerized scheme was applied to compute 92 global mammographic tissue density
      based features on each of four mammograms of the craniocaudal (CC) and
      mediolateral oblique (MLO) views. After adding three existing popular risk
      factors (woman's age, subjectively rated mammographic density, and family breast
      cancer history) into the initial feature pool, we applied a sequential forward
      floating selection feature selection algorithm to select relevant features from
      the bilateral CC and MLO view images separately. The selected CC and MLO view
      image features were used to train two artificial neural networks (ANNs). The
      results were then fused by a third ANN to build a two-stage classifier to predict
      the likelihood of the FFDM screening examination being positive. CAD performance
      was tested using a ten-fold cross-validation method. The computed area under the
      receiver operating characteristic curve was AUC = 0.779   +/-   0.025 and the
      odds ratio monotonically increased from 1 to 31.55 as CAD-generated detection
      scores increased. The study demonstrated that this new global image feature based
      CAD scheme had a relatively higher discriminatory power to cue the FFDM
      examinations with high risk of being positive, which may provide a new CAD-cueing
      method to assist radiologists in reading and interpreting screening mammograms.

PMID- 25984711
TI  - Implementation and Operational Research: Pulling the Network Together:
      Quasiexperimental Trial of a Patient-Defined Support Network Intervention for
      Promoting Engagement in HIV Care and Medication Adherence on Mfangano Island,
      Kenya.
AB  - BACKGROUND: Despite progress in the global scale-up of antiretroviral therapy,
      sustained engagement in HIV care remains challenging. Social capital is an
      important factor for sustained engagement, but interventions designed to harness
      this powerful social force are uncommon. METHODS: We conducted a
      quasiexperimental study evaluating the impact of the Microclinic Social Network
      intervention on engagement in HIV care and medication adherence on Mfangano
      Island, Kenya. The intervention was introduced into 1 of 4 similar communities
      served by this clinic; comparisons were made between communities using an
      intention-to-treat analysis. Microclinics, composed of patient-defined support
      networks, participated in 10 biweekly discussion sessions covering topics ranging
      from HIV biology to group support and group HIV status disclosure. Nevirapine
      concentrations in hair were measured before and after study. RESULTS: One hundred
      thirteen (74%) intervention community participants joined a microclinic group,
      86% of whom participated in group HIV status disclosure. Over 22-month follow-up,
      intervention community participants experienced one-half the rate of >= 90-day
      clinic absence as those in control communities (adjusted hazard ratio: 0.48; 95%
      confidence interval: 0.25 to 0.92). Nevirapine hair levels declined in both study
      arms; in adjusted linear regression analysis, the decline was 6.7 ng/mg less
      severe in the intervention arm than control arm (95% confidence interval: -2.7 to
      16.1). CONCLUSIONS: The microclinic intervention is a promising and feasible
      community-based strategy to improve long-term engagement in HIV care and possibly
      medication adherence. Reducing treatment interruptions using a social network
      approach has important implications for individual patient virologic suppression,
      morbidity, and mortality and for broader community empowerment and engagement in
      healthcare.

PMID- 25984712
TI  - Altered white matter integrity in individuals with cognitive vulnerability to
      depression: a tract-based spatial statistics study.
AB  - The microstructure of white matter in patients with major depressive disorder
      (MDD) has been demonstrated to be abnormal. However, it remains unclear whether
      these changes exist prior to the onset of disease. In this study, diffusion
      tensor imaging was used to evaluate white matter integrity in individuals who
      exhibited cognitive vulnerability to depression (CVD), MDD, and healthy controls
      (HC). Compared with the HC, MDD exhibited a lower fractional anisotropy (FA) in
      ten brain regions: the cerebral peduncle, the anterior and posterior limbs of the
      internal capsule (ALIC and PLIC), the external capsule, the retrolenticular part
      of the internal capsule (RLIC), the body and splenium of the corpus callosum, the
      superior and posterior corona radiata, and the cingulum. Moreover, CVD had
      significantly lower FA in the ALIC, the PLIC, the external capsule, the RLIC, the
      cerebral peduncle, and the superior corona radiata than did the HC. However, the
      white matter integrity was not significantly different between the CVD and MDD.
      These preliminary results indicate that alterations in the white matter observed
      in CVD may be a marker of vulnerability to MDD and that these alterations may
      exist prior to the onset of depression. 

PMID- 25984713
TI  - Influence of cellular trafficking pathway on bluetongue virus infection in ovine
      cells.
AB  - Bluetongue virus (BTV), a non-enveloped arbovirus, causes hemorrhagic disease in
      ruminants. However, the influence of natural host cell proteins on BTV
      replication process is not defined. In addition to cell lysis, BTV also exits non
      ovine cultured cells by non-lytic pathways mediated by nonstructural protein NS3
      that interacts with virus capsid and cellular proteins belonging to calpactin and
      ESCRT family. The PPXY late domain motif known to recruit NEDD4 family of HECT
      ubiquitin E3 ligases is also highly conserved in NS3. In this study using a
      mixture of molecular, biochemical and microscopic techniques we have analyzed the
      importance of ovine cellular proteins and vesicles in BTV infection. Electron
      microscopic analysis of BTV infected ovine cells demonstrated close association
      of mature particles with intracellular vesicles. Inhibition of Multi Vesicular
      Body (MVB) resident lipid phosphatidylinositol-3-phosphate resulted in decreased
      total virus titre suggesting that the vesicles might be MVBs. Proteasome mediated
      inhibition of ubiquitin or modification of virus lacking the PPXY in NS3 reduced
      virus growth. Thus, our study demonstrated that cellular components comprising of
      MVB and exocytic pathways proteins are involved in BTV replication in ovine
      cells.

PMID- 25984714
TI  - A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and
      Dengue (Novel Iminosugar Antiviral for Influenza and Dengue).
AB  - Iminosugars are capable of targeting the life cycles of multiple viruses by
      blocking host endoplasmic reticulum alpha-glucosidase enzymes that are required
      for competent replication of a variety of enveloped, glycosylated viruses.
      Iminosugars as a class are approved for use in humans with diseases such as
      diabetes and Gaucher's disease, providing evidence for safety of this class of
      compounds. The in vitro antiviral activity of iminosugars has been described in
      several publications with a subset of these demonstrating in vivo activity
      against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there
      is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy
      of iminosugars as antivirals has yet to be demonstrated in humans. In the current
      study, we report a novel iminosugar, UV-12, which has efficacy against dengue and
      influenza in mouse models. UV-12 exhibits drug-like properties including oral
      bioavailability and good safety profile in mice and guinea pigs. UV-12 is an
      example of an iminosugar with activity against multiple virus families that
      should be investigated in further safety and efficacy studies and demonstrates
      potential value of this drug class as antiviral therapeutics. 

PMID- 25984716
TI  - Submicron fungal fragments as another indoor biocontaminant in elementary
      schools.
AB  - There has been great concern about mold in school environments, but few
      comprehensive assessments of mold have been performed in such settings. Even
      spore counts or microscopic enumeration only may not be sufficient for evaluating
      fungal exposure. We explored the levels of submicron fungal fragments with
      potential heath impact due to their small size in elementary schools and
      investigated the variation in the concentrations of such particles before and
      after the rainy season. The concentrations of (1,3)-beta-D-glucan in submicron
      fungal fragments, airborne mold and bacteria, and PM10 were measured both indoors
      and outdoors in 70 classrooms at 8 elementary schools from May (before the rainy
      season) to July (after the rainy season) in 2012. Temperature and relative
      humidity were also monitored. We compared the levels of submicron fungal
      fragments among schools before and after the rainy season. The associations of
      the levels of submicron fungal fragments with other variables were analyzed.
      Overall, the concentrations of (1,3)-beta-D-glucan ranged from 10 to 347 pg m(
      3), and the indoor/outdoor ratios were greater than 1 in every school. After the
      rainy season, the (1,3)-beta-D-glucan concentrations decreased by about 35%, and
      similar significant decreases in the concentrations of airborne mold and bacteria
      and PM10 were observed. This difference was prominent for PM10 (P < 0.001). Only
      relative humidity was negatively associated with the concentration of submicron
      fungal fragments (P = 0.007). Our findings confirmed the comparable amounts of
      submicron fungal fragments in school environments. More comprehensive exposure
      assessments for smaller-sized fungal particles should be performed for better
      understanding of their health impact, particularly with regard to seasonal
      changes.

PMID- 25984715
TI  - Impact of Adenovirus E4-ORF3 Oligomerization and Protein Localization on Cellular
      Gene Expression.
AB  - The Adenovirus E4-ORF3 protein facilitates virus replication through the
      relocalization of cellular proteins into nuclear inclusions termed tracks. This
      sequestration event disrupts antiviral properties associated with target
      proteins. Relocalization of Mre11-Rad50-Nbs1 proteins prevents the DNA damage
      response from inhibiting Ad replication. Relocalization of PML and Daxx impedes
      the interferon-mediated antiviral response. Several E4-ORF3 targets regulate gene
      expression, linking E4-ORF3 to transcriptional control. Furthermore, E4-ORF3 was
      shown to promote the formation of heterochromatin, down-regulating p53-dependent
      gene expression. Here, we characterize how E4-ORF3 alters cellular gene
      expression. Using an inducible, E4-ORF3-expressing cell line, we performed
      microarray experiments to highlight cellular gene expression changes influenced
      by E4-ORF3 expression, identifying over four hundred target genes. Enrichment
      analysis of these genes suggests that E4-ORF3 influences factors involved in
      signal transduction and cellular defense, among others. The expression of mutant
      E4-ORF3 proteins revealed that nuclear track formation is necessary to induce
      these expression changes. Through the generation of knockdown cells, we
      demonstrate that the observed expression changes may be independent of Daxx and
      TRIM33 suggesting that an additional factor(s) may be responsible. The ability of
      E4-ORF3 to manipulate cellular gene expression through the sequestration of
      cellular proteins implicates a novel role for E4-ORF3 in transcriptional
      regulation.

PMID- 25984718
TI  - Single cell resolution in vivo imaging of DNA damage following PARP inhibition.
AB  - Targeting DNA repair pathways is a powerful strategy to treat cancers. To gauge
      efficacy in vivo, typical response markers include late stage effects such as
      tumor shrinkage, progression free survival, or invasive repeat biopsies. These
      approaches are often difficult to answer critical questions such as how a given
      drug affects single cell populations as a function of dose and time, distance
      from microvessels or how drug concentration (pharmacokinetics) correlates with
      DNA damage (pharmacodynamics). Here, we established a single-cell in vivo
      pharmacodynamic imaging read-out based on a truncated 53BP1 double-strand break
      reporter to determine whether or not poly(ADP-ribose) polymerase (PARP) inhibitor
      treatment leads to accumulation of DNA damage. Using this reporter, we show that
      not all PARP inhibitor treated tumors incur an increase in DNA damage. The method
      provides a framework for single cell analysis of cancer therapeutics in vivo. 

PMID- 25984719
TI  - Metabolic engineering: Biosensor keeps DOPA on track.

PMID- 25984720
TI  - An enzyme-coupled biosensor enables (S)-reticuline production in yeast from
      glucose.
AB  - Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized
      metabolites that include the pharmaceuticals codeine and morphine and their
      derivatives. Microbial synthesis of BIAs holds promise as an alternative to
      traditional crop-based manufacturing. Here we demonstrate the production of the
      key BIA intermediate (S)-reticuline from glucose in Saccharomyces cerevisiae. To
      aid in this effort, we developed an enzyme-coupled biosensor for the upstream
      intermediate L-3,4-dihydroxyphenylalanine (L-DOPA). Using this sensor, we
      identified an active tyrosine hydroxylase and improved its L-DOPA yields by 2.8
      fold via PCR mutagenesis. Coexpression of DOPA decarboxylase enabled what is to
      our knowledge the first demonstration of dopamine production from glucose in
      yeast, with a 7.4-fold improvement in titer obtained for our best mutant enzyme.
      We extended this pathway to fully reconstitute the seven-enzyme pathway from L
      tyrosine to (S)-reticuline. Future work to improve titers and connect these steps
      with downstream pathway branches, already demonstrated in S. cerevisiae, will
      enable low-cost production of many high-value BIAs. 

PMID- 25984721
TI  - Multiplexed Component Analysis to Identify Genes Contributing to the Immune
      Response during Acute SIV Infection.
AB  - Immune response genes play an important role during acute HIV and SIV infection.
      Using an SIV macaque model of AIDS and CNS disease, our overall goal was to
      assess how the expression of genes associated with immune and inflammatory
      responses are longitudinally changed in different organs or cells during SIV
      infection. To compare RNA expression of a panel of 88 immune-related genes across
      time points and among three tissues - spleen, mesenteric lymph nodes (MLN) and
      peripheral blood mononuclear cells (PBMC) - we designed a set of Nanostring
      probes. To identify significant genes during acute SIV infection and to
      investigate whether these genes are tissue-specific or have global roles, we
      introduce a novel multiplexed component analysis (MCA) method. This combines
      multivariate analysis methods with multiple preprocessing methods to create a set
      of 12 "judges"; each judge emphasizes particular types of change in gene
      expression to which cells could respond, for example, the absolute or relative
      size of expression change from baseline. Compared to bivariate analysis methods,
      our MCA method improved classification rates. This analysis allows us to identify
      three categories of genes: (a) consensus genes likely to contribute highly to the
      immune response; (b) genes that would contribute highly to the immune response
      only if certain assumptions are met - e.g. that the cell responds to relative
      expression change rather than absolute expression change; and (c) genes whose
      contribution to immune response appears to be modest. We then compared the
      results across the three tissues of interest; some genes are consistently highly
      contributing in all tissues, while others are specific for certain tissues. Our
      analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing
      genes, all of which are stimulated by type I interferon. This suggests that the
      cytokine storm during acute SIV infection is a systemic innate immune response
      against viral replication. Furthermore, these genes have approximately equal
      contributions to all tissues, making them possible candidates to be used as non
      invasive biomarkers in studying PBMCs instead of MLN and spleen during acute SIV
      infection experiments. We identified clusters of genes that co-vary together and
      studied their correlation with regard to other gene clusters. We also developed
      novel methods to faithfully visualize multi-gene correlations on two-dimensional
      polar plots, and to visualize tissue specificity of gene expression responses. 

PMID- 25984722
TI  - Gene and MicroRNA Expression Responses to Exercise; Relationship with Insulin
      Sensitivity.
AB  - BACKGROUND: Healthy individuals on the lower end of the insulin sensitivity
      spectrum also have a reduced gene expression response to exercise for specific
      genes. The goal of this study was to determine the relationship between insulin
      sensitivity and exercise-induced gene expression in an unbiased, global manner.
      METHODS AND FINDINGS: Euglycemic clamps were used to measure insulin sensitivity
      and muscle biopsies were done at rest and 30 minutes after a single acute
      exercise bout in 14 healthy participants. Changes in mRNA expression were
      assessed using microarrays, and miRNA analysis was performed in a subset of 6 of
      the participants using sequencing techniques. Following exercise, 215 mRNAs were
      changed at the probe level (Bonferroni-corrected P<0.00000115). Pathway and Gene
      Ontology analysis showed enrichment in MAP kinase signaling, transcriptional
      regulation and DNA binding. Changes in several transcription factor mRNAs were
      correlated with insulin sensitivity, including MYC, r=0.71; SNF1LK, r=0.69; and
      ATF3, r= 0.61 (5 corrected for false discovery rate). Enrichment in the 5'-UTRs
      of exercise-responsive genes suggested regulation by common transcription
      factors, especially EGR1. miRNA species of interest that changed after exercise
      included miR-378, which is located in an intron of the PPARGC1B gene.
      CONCLUSIONS: These results indicate that transcription factor gene expression
      responses to exercise depend highly on insulin sensitivity in healthy people. The
      overall pattern suggests a coordinated cycle by which exercise and insulin
      sensitivity regulate gene expression in muscle.

PMID- 25984724
TI  - Feeding Habits of Introduced Black Rats, Rattus rattus, in Nesting Colonies of
      Galapagos Petrel on San Cristobal Island, Galapagos.
AB  - Introduced rodents are responsible for ecosystem changes in islands around the
      world. In the Galapagos archipelago, their effects on the native flora and fauna
      are adverse, including the extinction of endemic rodents in some islands and the
      reduction in the reproductive success of the Galapagos petrel (Pterodroma
      phaeopygia) in its nesting zones. Understanding the feeding behavior of
      introduced rodents and their trophic interactions with native and non-native
      species on islands, can assist in the design of management strategies and
      conservation plans of invasive and endemic species respectively. Four petrel
      nesting colonies were monitored during June 2013 on San Cristobal Island (El
      Platano, El Junco, San Joaquin, and La Comuna). The feeding habits of black rats
      were evaluated by analyzing stomach contents and stable isotopes in hair. Three
      species of introduced rodents were captured. R. rattus was the most abundant at
      all sites (n=43, capture success (CS) = 55.8%), followed by the house mouse, Mus
      musculus (n = 17, CS = 37.8%), and the Norwegian rat, R. norvegicus (n = 4, CS =
      4.5%), captured only at La Comuna. The omnivorous black rat ate mostly plants
      (98%) and arthropods (2%). Intact seeds of Miconia robinsoniana were the main
      food at all sites (relative abundance=72.1%, present in 95% of the analyzed
      stomachs), showing the black rats' possible role in the archipelago as endemic
      seed dispersers. There was no evidence of petrel's intake; however, its possible
      consumption is not discarded at all. The delta15N and delta13C analysis
      corroborated the primarily herbivorous diet of black rats. The isotopic
      signatures of the three rodent species reflect the inter- and intra-specific
      differential use of food resources. Black rat showed a wider diet in La Comuna,
      which was related to a lower availability of its primary prey and its ability to
      adapt to the available resources in its habitat. 

PMID- 25984723
TI  - The Association between Mycobacterium Tuberculosis Genotype and Drug Resistance
      in Peru.
AB  - BACKGROUND: The comparison of Mycobacterium tuberculosis bacterial genotypes with
      phenotypic, demographic, geospatial and clinical data improves our understanding
      of how strain lineage influences the development of drug-resistance and the
      spread of tuberculosis. METHODS: To investigate the association of Mycobacterium
      tuberculosis bacterial genotype with drug-resistance. Drug susceptibility testing
      together with genotyping using both 15-loci MIRU-typing and spoligotyping, was
      performed on 2,139 culture positive isolates, each from a different patient in
      Lima, Peru. Demographic, geospatial and socio-economic data were collected using
      questionnaires, global positioning equipment and the latest national census.
      RESULTS: The Latin American Mediterranean (LAM) clade (OR 2.4, p<0.001) was
      significantly associated with drug-resistance and alone accounted for more than
      half of all drug resistance in the region. Previously treated patients, prisoners
      and genetically clustered cases were also significantly associated with drug
      resistance (OR's 2.5, 2.4 and 1.8, p<0.001, p<0.05, p<0.001 respectively).
      CONCLUSIONS: Tuberculosis disease caused by the LAM clade was more likely to be
      drug resistant independent of important clinical, genetic and socio-economic
      confounding factors. Explanations for this include; the preferential co-evolution
      of LAM strains in a Latin American population, a LAM strain bacterial genetic
      background that favors drug-resistance or the "founder effect" from pre-existing
      LAM strains disproportionately exposed to drugs.

PMID- 25984726
TI  - Identification of Leaf Proteins Differentially Accumulated between Wheat
      Cultivars Distinct in Their Levels of Drought Tolerance.
AB  - The drought-tolerant 'Ningchun 47' (NC47) and drought-sensitive 'Chinese Spring'
      (CS) wheat (Triticum aestivum L.) cultivars were treated with different PEG6000
      concentrations at the three-leaf stage. An analysis on the physiological and
      proteomic changes of wheat seedling in response to drought stress was performed.
      In total, 146 differentially accumulated protein (DAP) spots were separated and
      recognised using two-dimensional gel electrophoresis. In total, 101 DAP spots
      representing 77 unique proteins were identified by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry. These proteins were
      allocated to 10 groups according to putative functions, which were mainly
      involved in carbon metabolism (23.4%), photosynthesis/respiration (22.1%) and
      stress/defence/detoxification (18.2%). Some drought stress-related proteins in
      NC47, such as enolase, 6-phosphogluconate dehydrogenase, Oxygen-evolving enhancer
      protein 2, fibrillin-like protein, 2-Cys peroxiredoxin BAS1 and 70-kDa heat shock
      protein, were more upregulated than those in CS. Multivariate principal
      components analysis revealed obvious differences between the control and
      treatments in both NC47 and CS, while cluster analysis showed that the DAPs
      displayed five and six accumulation patterns in NC47 and CS, respectively.
      Protein-protein interaction network analysis showed that some key DAPs, such as 2
      Cys peroxiredoxin BAS1, RuBisCO large subunit-binding protein, 50S ribosomal
      protein L1, 6-phosphogluconate dehydrogenase, glyceraldehyde 3-phosphate
      dehydrogenase isoenzyme and 70-kDa heat shock protein, with upregulated
      accumulation in NC47, had complex interactions with other proteins related to
      amino acid metabolism, carbon metabolism, energy pathway, signal transduction,
      stress/defence/detoxification, protein folding and nucleotide metabolism. These
      proteins could play important roles in drought-stress tolerance and contribute to
      the relatively stronger drought tolerance of NC47. 

PMID- 25984728
TI  - The development of social brain functions in infancy.
AB  - One fundamental question in psychology is what makes humans such intensely social
      beings. Probing the developmental and neural origins of our social capacities is
      a way of addressing this question. In the last 10 years the field of social
      cognitive development has witnessed a surge in studies using neuroscience methods
      to elucidate the development of social information processing during infancy.
      While the use of electroencephalography (EEG)/event-related brain potentials
      (ERPs) and functional near-infrared spectroscopy (fNIRS) has revealed a great
      deal about the timing and localization of the cortical processes involved in
      early social cognition, the principles underpinning the early development of
      social brain functioning remain largely unexplored. Here I provide a framework
      that delineates the essential processes implicated in the early development of
      the social brain. In particular, I argue that the development of social brain
      functions in infancy is characterized by the following key principles: (a) self
      relevance, (b) joint engagement, (c) predictability, (d) categorization, (e)
      discrimination, and (f) integration. For all of the proposed principles, I
      provide empirical examples to illustrate when in infancy they emerge. Moreover, I
      discuss to what extent they are in fact specifically social in nature or share
      properties with more domain-general developmental principles. Taken together,
      this article provides a conceptual integration of the existing EEG/ERPs and fNIRS
      work on infant social brain function and thereby offers the basis for a principle
      based approach to studying the neural correlates of early social cognition.

PMID- 25984727
TI  - Combining Next Generation Sequencing with Bulked Segregant Analysis to Fine Map a
      Stem Moisture Locus in Sorghum (Sorghum bicolor L. Moench).
AB  - Sorghum is one of the most promising bioenergy crops. Stem juice yield, together
      with stem sugar concentration, determines sugar yield in sweet sorghum. Bulked
      segregant analysis (BSA) is a gene mapping technique for identifying genomic
      regions containing genetic loci affecting a trait of interest that when combined
      with deep sequencing could effectively accelerate the gene mapping process. In
      this study, a dry stem sorghum landrace was characterized and the stem water
      controlling locus, qSW6, was fine mapped using QTL analysis and the combined BSA
      and deep sequencing technologies. Results showed that: (i) In sorghum variety
      Jiliang 2, stem water content was around 80% before flowering stage. It dropped
      to 75% during grain filling with little difference between different internodes.
      In landrace G21, stem water content keeps dropping after the flag leaf stage. The
      drop from 71% at flowering time progressed to 60% at grain filling time. Large
      differences exist between different internodes with the lowest (51%) at the 7th
      and 8th internodes at dough stage. (ii) A quantitative trait locus (QTL)
      controlling stem water content mapped on chromosome 6 between SSR markers Ch6-2
      and gpsb069 explained about 34.7-56.9% of the phenotypic variation for the 5th to
      10th internodes, respectively. (iii) BSA and deep sequencing analysis narrowed
      the associated region to 339 kb containing 38 putative genes. The results could
      help reveal molecular mechanisms underlying juice yield of sorghum and thus to
      improve total sugar yield. 

PMID- 25984725
TI  - Inferring Broad Regulatory Biology from Time Course Data: Have We Reached an
      Upper Bound under Constraints Typical of In Vivo Studies?
AB  - There is a growing appreciation for the network biology that regulates the
      coordinated expression of molecular and cellular markers however questions
      persist regarding the identifiability of these networks. Here we explore some of
      the issues relevant to recovering directed regulatory networks from time course
      data collected under experimental constraints typical of in vivo studies. NetSim
      simulations of sparsely connected biological networks were used to evaluate two
      simple feature selection techniques used in the construction of linear Ordinary
      Differential Equation (ODE) models, namely truncation of terms versus latent
      vector projection. Performance was compared with ODE-based Time Series Network
      Identification (TSNI) integral, and the information-theoretic Time-Delay ARACNE
      (TD-ARACNE). Projection-based techniques and TSNI integral outperformed
      truncation-based selection and TD-ARACNE on aggregate networks with edge
      densities of 10-30%, i.e. transcription factor, protein-protein cliques and
      immune signaling networks. All were more robust to noise than truncation-based
      feature selection. Performance was comparable on the in silico 10-node DREAM 3
      network, a 5-node Yeast synthetic network designed for In vivo Reverse
      engineering and Modeling Assessment (IRMA) and a 9-node human HeLa cell cycle
      network of similar size and edge density. Performance was more sensitive to the
      number of time courses than to sample frequency and extrapolated better to larger
      networks by grouping experiments. In all cases performance declined rapidly in
      larger networks with lower edge density. Limited recovery and high false positive
      rates obtained overall bring into question our ability to generate informative
      time course data rather than the design of any particular reverse engineering
      algorithm. 

PMID- 25984729
TI  - Identifying Organizational Identification as a Basis for Attitudes and Behaviors:
      A Meta-Analytic Review.
AB  - Organizational identification has been argued to have a unique value in
      explaining individual attitudes and behaviors in organizations, as it involves
      the essential definition of entities (i.e., individual and organizational
      identities). This review seeks meta-analytic evidence of the argument by
      examining how this identity-relevant construct functions in the nexus of
      attitudinal/behavioral constructs. The findings show that, first, organizational
      identification is significantly associated with key attitudes (job involvement,
      job satisfaction, and affective organizational commitment) and behaviors (in-role
      performance and extra-role performance) in organizations. Second, in the classic
      psychological model of attitude-behavior relations (Fishbein & Ajzen, 1975),
      organizational identification is positioned as a basis from which general sets of
      those attitudes and behaviors are engendered; organizational identification has a
      direct effect on general behavior above and beyond the effect of general
      attitude. Third, the effects of organizational identification are moderated by
      national culture, a higher-level social context wherein the organization is
      embedded, such that the effects are stronger in a collectivistic culture than in
      an individualistic culture. Theoretical and practical implications of the
      findings and future research directions are discussed.

PMID- 25984730
TI  - Vascular endothelial growth factor (-460 C/T, +405 G/C, and +936 C/T)
      polymorphisms and endometriosis risk in Tunisian population.
AB  - The vascular endothelial growth factor (VEGF), a major angiogenic factor, is
      known to play an important role in the development of endometriosis. The aim of
      this study was to investigate the association of three VEGF (-460 C/T, +405 G/C,
      and +936 C/T) polymorphisms with the risk of endometriosis in the Tunisian
      population. This study includes 105 women with endometriosis and 150 women with
      no laparoscopic evidence of disease. Genotyping of the VEGF -460 C/T, +405 G/C,
      and +936 C/T polymorphisms were performed by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). The distribution of
      genotypes (P = 0.006) and allele (P = 0.0009) frequencies of the +936 C/T
      polymorphism was significantly different between patients and controls. Patients
      with stages III-IV endometriosis showed a higher VEGF + 936T allele frequency
      than controls (P = 0.0001). However, the distribution of genotypes and allele
      frequencies of the VEGF -460 C/T and +405 G/C polymorphisms did not differ
      significantly between endometriosis patients and controls. These findings suggest
      that the VEGF +936 C/T polymorphism may be a risk factor for endometriosis
      development and the VEGF +936 T allele is associated with an increased risk of
      stages III-IV endometriosis in the Tunisian population. 

PMID- 25984731
TI  - The prognostic utility of tests of platelet function for the detection of
      'aspirin resistance' in patients with established cardiovascular or
      cerebrovascular disease: a systematic review and economic evaluation.
AB  - BACKGROUND: The use of aspirin is well established for secondary prevention of
      cardiovascular disease. However, a proportion of patients suffer repeat
      cardiovascular events despite being prescribed aspirin treatment. It is uncertain
      whether or not this is due to an inherent inability of aspirin to sufficiently
      modify platelet activity. This report aims to investigate whether or not
      insufficient platelet function inhibition by aspirin ('aspirin resistance'), as
      defined using platelet function tests (PFTs), is linked to the occurrence of
      adverse clinical outcomes, and further, whether or not patients at risk of future
      adverse clinical events can be identified through PFTs. OBJECTIVES: To review
      systematically the clinical effectiveness and cost-effectiveness evidence
      regarding the association between PFT designation of 'aspirin resistance' and the
      risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To
      undertake exploratory model-based cost-effectiveness analysis on the use of PFTs.
      DATA SOURCES: Bibliographic databases (e.g. MEDLINE from inception and EMBASE
      from 1980), conference proceedings and ongoing trial registries up to April 2012.
      METHODS: Standard systematic review methods were used for identifying clinical
      and cost studies. A risk-of-bias assessment tool was adapted from checklists for
      prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the
      association between 'aspirin resistance', for different PFTs, and clinical
      outcomes are presented; however, heterogeneity between studies precluded pooling
      of results. A speculative economic model of a PFT and change of therapy strategy
      was developed. RESULTS: One hundred and eight relevant studies using a variety of
      PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results
      indicated that some PFTs may have some prognostic utility, i.e. a trend for more
      clinical events to be associated with groups classified as 'aspirin resistant'.
      Methodological and clinical heterogeneity prevented a quantitative summary of
      prognostic effect. Study-level effect sizes were generally small and absolute
      outcome risk was not substantially different between 'aspirin resistant' and
      'aspirin sensitive' designations. No studies on the cost-effectiveness of PFTs
      for 'aspirin resistance' were identified. Based on assumptions of PFTs being able
      to accurately identify patients at high risk of clinical events and such patients
      benefiting from treatment modification, the economic model found that a test
      treat strategy was likely to be cost-effective. However, neither assumption is
      currently evidence based. LIMITATIONS: Poor or incomplete reporting of studies
      suggests a potentially large volume of inaccessible data. Analyses were confined
      to studies on patients prescribed aspirin as sole antiplatelet therapy at the
      time of PFT. Clinical and methodological heterogeneity across studies precluded
      meta-analysis. Given the lack of robust data the economic modelling was
      speculative. CONCLUSIONS: Although evidence indicates that some PFTs may have
      some prognostic value, methodological and clinical heterogeneity between studies
      and different approaches to analyses create confusion and inconsistency in
      prognostic results, and prevented a quantitative summary of their prognostic
      effect. Protocol-driven and adequately powered primary studies are needed, using
      standardised methods of measurements to evaluate the prognostic ability of each
      test in the same population(s), and ideally presenting individual patient data.
      For any PFT to inform individual risk prediction, it will likely need to be
      considered in combination with other prognostic factors, within a prognostic
      model. STUDY REGISTRATION: This study is registered as PROSPERO
      2012:CRD42012002151. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 25984732
TI  - Toxic cyanobacterial bloom triggers in missisquoi bay, lake champlain, as
      determined by next-generation sequencing and quantitative PCR.
AB  - Missisquoi Bay (MB) is a temperate eutrophic freshwater lake that frequently
      experiences toxic Microcystis-dominated cyanobacterial blooms. Non-point sources
      are responsible for the high concentrations of phosphorus and nitrogen in the
      bay. This study combined data from environmental parameters, E. coli counts, high
      throughput sequencing of 16S rRNA gene amplicons, quantitative PCR (16S rRNA and
      mcyD genes) and toxin analyses to identify the main bloom-promoting factors. In
      2009, nutrient concentrations correlated with E. coli counts, abundance of total
      cyanobacterial cells, Microcystis 16S rRNA and mcyD genes and intracellular
      microcystin. Total and dissolved phosphorus also correlated significantly with
      rainfall. The major cyanobacterial taxa were members of the orders Chroococcales
      and Nostocales. The genus Microcystis was the main mcyD-carrier and main
      microcystin producer. Our results suggested that increasing nutrient
      concentrations and total nitrogen:total phosphorus (TN:TP) ratios approaching
      11:1, coupled with an increase in temperature, promoted Microcystis-dominated
      toxic blooms. Although the importance of nutrient ratios and absolute
      concentrations on cyanobacterial and Microcystis dynamics have been documented in
      other laboratories, an optimum TN:TP ratio for Microcystis dominance has not been
      previously observed in situ. This observation provides further support that
      nutrient ratios are an important determinant of species composition in natural
      phytoplankton assemblages. 

PMID- 25984733
TI  - "Altiarchaeales": uncultivated archaea from the subsurface.
AB  - Due to the limited cultivability of the vast majority of microorganisms,
      researchers have applied environmental genomics and other state-of-the-art
      technologies to gain insights into the biology of uncultivated Archaea and
      bacteria in their natural biotope. In this review, we summarize the scientific
      findings on a recently proposed order-level lineage of uncultivated Archaea
      called Altiarchaeales, which includes "Candidatus Altiarchaeum hamiconexum" as
      the most well-described representative. Ca. A. hamiconexum possesses a complex
      biology: thriving strictly anaerobically, this microorganism is capable of
      forming highly-pure biofilms, connecting the cells by extraordinary cell surface
      appendages (the "hami") and has other highly unusual traits, such as a double
      membrane-based cell wall. Indicated by genomic information from different
      biotopes, the Altiarchaeales seem to proliferate in deep, anoxic groundwater of
      Earth's crust bearing a potentially very important function: carbon fixation.
      Although their net carbon fixation rate has not yet been determined, they appear
      as highly abundant organisms in their biotopes and may thus represent an
      important primary producer in the subsurface. In sum, the research over more than
      a decade on Ca. A. hamiconexum has revealed many interesting features of its
      lifestyle, its genomic information, metabolism and ultrastructure, making this
      archaeon one of the best-studied uncultivated Archaea in the literature. 

PMID- 25984734
TI  - What makes a peer a peer?
AB  - OBJECTIVE: The purpose of this study was to learn more about which
      characteristics are considered important for consumers to feel that a person is
      their peer. METHODS: Forty-one participants in a jail diversion program for
      veterans were asked to rate characteristics in terms of importance for acting in
      a peer support role. Differences by gender, combat exposure, trauma history, and
      mental health and substance abuse treatment were analyzed using t tests and
      Pearson correlations. RESULTS: Having served in the military had the highest
      average rating; trauma experience second. Participants with combat experience
      were significantly more likely than those without to indicate this as an
      important characteristic. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Increasingly
      behavioral health programs are recognizing the importance of peer involvement.
      This study offers guidance on who should be designated a "peer," suggesting that
      this should vary according to the population served and be based on the
      perceptions of the consumers.

PMID- 25984735
TI  - Current status of psychiatric rehabilitation in Portugal: A national survey.
AB  - OBJECTIVE: This article reports on the current state of psychiatric
      rehabilitation in Portugal. METHOD: A paper-and-pencil survey was sent to 70
      institutions to inquire about the provision of psychiatric rehabilitation
      services and programs. RESULTS: With a response rate of 40%, 14% of institutions
      indicated that supported education was provided, 36% offered nonmainstream
      vocational training, and 29% provided supported employment; none provided
      evidence-based Individual Placement and Support. Permanent group homes in the
      community (29%) followed by transitional group homes on institutional grounds
      (18%) were the most common residential services, with supported housing services
      (14%) offered less frequently. Finally, 93% of institutions offered occupational
      activities, 61% provided multifamily psychoeducation, and 36% provided single
      family psychoeducation. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Despite recent
      national initiatives promoting effective psychiatric rehabilitation services,
      supported employment, supported education, and supported housing are not widely
      implemented in Portugal. To achieve better outcomes for clients, it is critical
      that evidence-based and promising practices be extensively disseminated.

PMID- 25984736
TI  - Working therapeutically with deaf people recovering from trauma and addiction.
AB  - OBJECTIVE: This article reviews what is known about behavioral health treatment
      of deaf persons with comorbid trauma and addiction. METHOD: We discuss how to
      work therapeutically with deaf people with comorbid trauma and addiction, both
      through a review of the literature and through clinical observations of the
      authors. The article also includes the personal stories of two people-a Deaf peer
      specialist and a hearing psychiatrist-who share their humbling stories about the
      recovery process for deaf people and the challenges of learning to become an
      effective Deaf mental health care provider. FINDINGS: Deaf people report higher
      rates of mental health problems than the general population. Although initial
      empirical work with the deaf population suggests high rates of posttraumatic
      stress disorder (PTSD) and substance use disorder (SUD), little is known about
      the rates of comorbid PTSD/SUD or how to effectively address this comorbidity in
      treatment. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Substantial work is needed
      to raise awareness of comorbid PTSD/SUD and provide treatment tools to agencies
      and providers who work with deaf clients, infusing trauma-informed care into deaf
      SUD services and SUD treatment into deaf mental health care. Fortunately, several
      endeavors are on the horizon to disseminate assessment and treatment tools to
      work with deaf people recovering from trauma and addiction.

PMID- 25984737
TI  - Health disparities among youth with type 1 diabetes: A systematic review of the
      current literature.
AB  - INTRODUCTION: Research in pediatric Type 1 diabetes (T1D) has reliably identified
      differences in health outcomes based on race/ethnicity and socioeconomic status
      (SES). Racial/ethnic minority and/or low-SES youth consistently display poorer
      physical health and psychological functioning than racial/ethnic majority and
      higher-SES youth. The purpose of this review is to better understand health
      disparities in T1D by race/ethnicity and SES, and to provide recommendations for
      researchers based on these findings. METHODS: Articles were obtained from
      PsycINFO, PubMed, and Web of Knowledge with search terms: "Type 1 diabetes,"
      "ethnic," "pediatric," "race/ethnicity," "race," "socioeconomic status," "SES,"
      and "income." Criteria for inclusion were (a) Type 1 diabetes cases, (b) child or
      adolescent samples, (c) information about health or psychosocial outcomes grouped
      by race/ethnicity or SES, (d) no intervention data, (e) peer-reviewed, (f),
      English-language, and (g) published in an academic journal. RESULTS: Twenty-seven
      articles reported on health outcomes and 4 articles reported on psychosocial
      outcomes. Across 16 studies, racial/ethnic minority youth displayed higher HbA1c
      levels compared to Caucasian youth. Eighteen studies reported that lower-SES
      youth had higher HbA1c levels than higher-SES youth. Four studies found
      racial/ethnic minority youth and lower-SES youth had poorer psychological
      functioning than Caucasian youth or higher-SES youth. DISCUSSION: Findings from
      our review suggest an association between race/ethnicity, SES, and health
      outcomes in pediatric T1D. Researchers should consider developing interventions
      that take into account factors which may place children from racial/ethnic
      minority and lower-SES backgrounds at risk for poor metabolic control and
      emotional functioning. Future research should examine causative mechanisms of
      health disparities.

PMID- 25984738
TI  - Nutrient patterns and their association with socio-demographic, lifestyle factors
      and obesity risk in rural South African adolescents.
AB  - The aim of this study was to identify and describe the diversity of nutrient
      patterns and how they associate with socio-demographic and lifestyle factors
      including body mass index in rural black South African adolescents. Nutrient
      patterns were identified from quantified food frequency questionnaires (QFFQ) in
      388 rural South African adolescents between the ages of 11-15 years from the
      Agincourt Health and Socio-demographic Surveillance System (AHDSS). Principle
      Component Analysis (PCA) was applied to 25 nutrients derived from QFFQs. Multiple
      linear regression and partial R2 models were fitted and computed respectively for
      each of the retained principal component (PC) scores on socio-demographic and
      lifestyle characteristics including body mass index (BMI) for age Z scores. Four
      nutrient patterns explaining 79% of the total variance were identified: PCI (26%)
      was characterized by animal derived nutrients; PC2 (21%) by vitamins, fibre and
      vegetable oil nutrients; PC3 (19%) by both animal and plant derived nutrients
      (mixed diet driven nutrients); and PC4 (13%) by starch and folate. A positive and
      significant association was observed with BMI for age Z scores per 1 standard
      deviation (SD) increase in PC1 (0.13 (0.02; 0.24); p = 0.02) and PC4 (0.10 (
      0.01; 0.21); p = 0.05) scores only. We confirmed variability in nutrient patterns
      that were significantly associated with various lifestyle factors including
      obesity. 

PMID- 25984739
TI  - MiRNA-194 Regulates Palmitic Acid-Induced Toll-Like Receptor 4 Inflammatory
      Responses in THP-1 Cells.
AB  - There is strong evidence to suggest that inflammatory responses link obesity and
      diseases, and the understanding of obesity-induced inflammatory mechanisms is
      central to the pathogenesis of diseases such asnonalcoholic fatty liver
      disease(NAFLD) and atherosclerosis that are modified by obesity. Based on this,
      anti-inflammatory treatments become a potential therapies for obesity-related
      diseases like NAFLD.A critical role of toll-like receptor (TLR) and its
      downstream molecules such as tumor necrosis factor receptor-associated factor
      6(TRAF6) has been documented in inflammatory response induced by fatty acid. TLR
      pathway regulation provides a new insight to controlling the inflammatory
      response induced by fatty acid. Taken together, our study was aimed to understand
      the mechanism of fatty acid-mediated inflammation and look for an effective
      target which can prevent the inflammatory response induced by obesity. In this
      study, we used the saturated fatty acid palmitic acid (PA) to activate TLR4
      signal pathway in human monocyte cells THP-1 that established an intracellular
      inflammatory model. Followed with activated TLR4, downstream molecular TRAF6 was
      upregulated and ultimately induced proinflammatory cytokine production. Based on
      this model, we also found that PA downregulated miR-194 expression with TLR4
      activation. Moreover, our results showed that key signal molecular TRAF6 is a
      target of miR-194, overexpression of miR-194 directly decreased TRAF6 expression
      and attenuated the release of proinflammatory cytokine TNF-alpha in PA-activated
      monocyte THP-1. We conclude that miR-194 negatively regulates the TLR4 signal
      pathway which is activated by PA through directly negative TRAF6 expression. 

PMID- 25984740
TI  - Impacts of Maternal Nutrition on Vascularity of Nutrient Transferring Tissues
      during Gestation and Lactation.
AB  - As the demand for food increases with exponential growth in the world population,
      it is imperative that we understand how to make livestock production as efficient
      as possible in the face of decreasing available natural resources. Moreover, it
      is important that livestock are able to meet their metabolic demands and supply
      adequate nutrition to developing offspring both during pregnancy and lactation.
      Specific nutrient supplementation programs that are designed to offset
      deficiencies, enhance efficiency, and improve nutrient supply during pregnancy
      can alter tissue vascular responses, fetal growth, and postnatal offspring
      outcomes. This review outlines how vascularity in nutrient transferring tissues,
      namely the maternal gastrointestinal tract, the utero-placental tissue, and the
      mammary gland, respond to differing nutritional planes and other specific
      nutrient supplementation regimes. 

PMID- 25984741
TI  - Suboptimal Micronutrient Intake among Children in Europe.
AB  - Adequate dietary intake of micronutrients is not necessarily achieved even in
      resource-rich areas of the world wherein overeating is a public health concern.
      In Europe, population-based data suggests substantial variability in
      micronutrient intake among children. Two independent surveys of micronutrient
      consumption among European children were evaluated. Stratified by age, the data
      regarding micronutrient intake were evaluated in the context of daily
      requirements, which are typically estimated in the absence of reliable absolute
      values derived from prospective studies. The proportion of children living in
      Europe whose intake of at least some vitamins and trace elements are at or below
      the estimated average requirements is substantial. The most common deficiencies
      across age groups included vitamin D, vitamin E, and iodine. Specific
      deficiencies were not uniform across countries or by age or gender. 
      Micronutrient intake appears to be more strongly influenced by factors other than
      access to food. Substantial portions of European children may be at risk of
      reversible health risks from inadequate intake of micronutrients. Despite the
      growing health threat posed by excess intake of calories, adequate exposure to
      vitamins, trace elements, and other micronutrients may deserve attention in
      public health initiatives to optimize growth and development in the European
      pediatric population. 

PMID- 25984743
TI  - Does an Adolescent's Accuracy of Recall Improve with a Second 24-h Dietary
      Recall?
AB  - The multiple-pass 24-h dietary recall is used in most national dietary surveys.
      Our purpose was to assess if adolescents' accuracy of recall improved when a 5
      step multiple-pass 24-h recall was repeated. Participants (n = 24), were Chinese
      American youths aged between 11 and 15 years and lived in a supervised
      environment as part of a metabolic feeding study. The 24-h recalls were conducted
      on two occasions during the first five days of the study. The four steps (quick
      list; forgotten foods; time and eating occasion; detailed description of the
      food/beverage) of the 24-h recall were assessed for matches by category.
      Differences were observed in the matching for the time and occasion step (p <
      0.01), detailed description (p < 0.05) and portion size matching (p < 0.05).
      Omission rates were higher for the second recall (p < 0.05 quick list; p < 0.01
      forgotten foods). The adolescents over-estimated energy intake on the first
      (11.3% +/- 22.5%; p < 0.05) and second recall (10.1% +/- 20.8%) compared with the
      known food and beverage items. These results suggest that the adolescents'
      accuracy to recall food items declined with a second 24-h recall when repeated
      over two non-consecutive days. 

PMID- 25984742
TI  - Redox-active selenium compounds--from toxicity and cell death to cancer
      treatment.
AB  - Selenium is generally known as an antioxidant due to its presence in
      selenoproteins as selenocysteine, but it is also toxic. The toxic effects of
      selenium are, however, strictly concentration and chemical species dependent. One
      class of selenium compounds is a potent inhibitor of cell growth with remarkable
      tumor specificity. These redox active compounds are pro-oxidative and highly
      cytotoxic to tumor cells and are promising candidates to be used in chemotherapy
      against cancer. Herein we elaborate upon the major forms of dietary selenium
      compounds, their metabolic pathways, and their antioxidant and pro-oxidant
      potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of
      inorganic selenite and organic selenocystine compounds to different cancer cells
      are presented as evidence to our perspective. Furthermore, new novel classes of
      selenium compounds specifically designed to target tumor cells are presented and
      the potential of selenium in modern oncology is extensively discussed. 

PMID- 25984744
TI  - Diet Soft Drink Consumption is Associated with the Metabolic Syndrome: A Two
      Sample Comparison.
AB  - Comparative analyses of soft drink intakes in samples from the United States and
      Europe, and assessed intakes in relation to prevalence of metabolic syndrome
      (MetS) and its individual components are currently lacking. We used data
      collected on cardiovascular health and dietary intakes in participants from two
      cross-sectional studies: the Maine-Syracuse Longitudinal Study (MSLS), conducted
      in Central New York, USA in 2001-2006 (n = 803), and the Observation of
      Cardiovascular Risk Factors in Luxembourg Study (ORISCAV-LUX), conducted in 2007
      2009 (n = 1323). Odds ratios for MetS were estimated according to type and
      quantity of soft drink consumption, adjusting for demographic, lifestyle and
      dietary factors, in both studies. In both studies, individuals who consumed at
      least one soft drink per day had a higher prevalence of MetS, than non-consumers.
      This was most evident for consumers of diet soft drinks, consistent across both
      studies. Diet soft drink intakes were also positively associated with waist
      circumference and fasting plasma glucose in both studies. Despite quite different
      consumption patterns of diet versus regular soft drinks in the two studies,
      findings from both support the notion that diet soft drinks are associated with a
      higher prevalence of MetS. 

PMID- 25984746
TI  - HPLC-DAD-MS Profiling of Polyphenols Responsible for the Yellow-Orange Color in
      Apple Juices of Different French Cider Apple Varieties.
AB  - The pigments responsible for the yellow-orange coloration of apple juices have
      remained largely unknown up to now. Four French cider apple juices were produced
      in conditions similar to those used in the cider-making industry. The oxidized
      juices, characterized using the CIE L a b parameters, displayed various colors
      depending on the apple variety and native phenolic composition. HPLC-DAD-MS
      revealed contrasting pigment profiles related to oxidized tanning and nontanning
      molecules. The latter were divided into two groups according to their polarity
      and their visible spectra. With regard to phenolic classes, flavanol monomers and
      hydroxycinnamic acids played an essential role in the formation of oxidation
      products. Interestingly, dihydrochalcones appeared to include precursors of some
      yellow compounds. Indeed, the yellow pigment phloretin xyloglucoside oxidation
      product (PXGOPj), derived from phloretin xyloglucoside, was clearly identified in
      apple juices as a xyloglucose analogue of the yellow pigment phloridzin oxidation
      product (POPj), previously characterized in a model solution by Le Guerneve et
      al. (Tetrahedron Lett. 2004, 45 (35), 6673-6677). 

PMID- 25984745
TI  - Cross-continental comparison of national food consumption survey methods--a
      narrative review.
AB  - Food consumption surveys are performed in many countries. Comparison of results
      from those surveys across nations is difficult because of differences in
      methodological approaches. While consensus about the preferred methodology
      associated with national food consumption surveys is increasing, no inventory of
      methodological aspects across continents is available. The aims of the present
      review are (1) to develop a framework of key methodological elements related to
      national food consumption surveys, (2) to create an inventory of these properties
      of surveys performed in the continents North-America, South-America, Asia and
      Australasia, and (3) to discuss and compare these methodological properties cross
      continentally. A literature search was performed using a fixed set of search
      terms in different databases. The inventory was completed with all accessible
      information from all retrieved publications and corresponding authors were
      requested to provide additional information where missing. Surveys from ten
      individual countries, originating from four continents are listed in the
      inventory. The results are presented according to six major aspects of food
      consumption surveys. The most common dietary intake assessment method used in
      food consumption surveys worldwide is the 24-HDR (24 h dietary recall),
      occasionally administered repeatedly, mostly using interview software. Only three
      countries have incorporated their national food consumption surveys into
      continuous national health and nutrition examination surveys. 

PMID- 25984747
TI  - High-Performance and Stable Gel-State Dye-Sensitized Solar Cells Using Anodic
      TiO2 Nanotube Arrays and Polymer-Based Gel Electrolytes.
AB  - Highly ordered and vertically oriented TiO2 nanotube (NT) arrays were synthesized
      with potentiostatic anodization of Ti foil and applied to fabricate gel-state dye
      sensitized solar cells (DSSCs). The open structure of the TiO2 NT facilitates the
      infiltration of the gel-state electrolyte; their one-dimensional structural
      feature provides effective charge transport. TiO2 NTs of length L=15-35 MUm were
      produced on anodization for periods of t=5-15 h at a constant voltage of 60 V,
      and sensitized with N719 for photovoltaic characterization. A commercially
      available copolymer, poly(methyl methacrylate-co-ethyl acrylate) (PMMA-EA),
      served as a gelling agent to prepare a polymer-gel electrolyte (PGE) for DSSC
      applications. The PGE as prepared exhibited a maximum conductivity of 4.58 mS cm(
      1) with PMMA-EA (7 wt %). The phase transition temperature (Tp) of the PGE
      containing PMMA-EA at varied concentrations was determined on the basis of the
      viscosities measured at varied temperatures. Tp increased with increasing
      concentration of PMMA-EA. An NT-DSSC with L=30 MUm assembled using a PGE
      containing PMMA-EA (7 wt %) exhibited an overall power conversion efficiency
      (PCE) of 6.9%, which is comparable with that of a corresponding liquid-type
      device, PCE=7.1%. Moreover, the gel-state NT-DSSC exhibited excellent thermal and
      light-soaking enduring stability: the best device retained ~90% of its initial
      efficiency after 1000 h under 1 sun of illumination at 50  degrees C, whereas its
      liquid-state counterpart decayed appreciably after light soaking for 500 h.

PMID- 25984748
TI  - Redox Non-innocent Ligand Controls Water Oxidation Overpotential in a New Family
      of Mononuclear Cu-Based Efficient Catalysts.
AB  - A new family of tetra-anionic tetradentate amidate ligands, N1,N1'-(1,2
      phenylene)bis(N2-methyloxalamide) (H4L1), and its derivatives containing electron
      donating groups at the aromatic ring have been prepared and characterized,
      together with their corresponding anionic Cu(II) complexes, [(LY)Cu](2-). At pH
      11.5, the latter undergoes a reversible metal-based III/II oxidation process at
      0.56 V and a ligand-based pH-dependent electron-transfer process at 1.25 V,
      associated with a large electrocatalytic water oxidation wave (overpotential of
      700 mV). Foot-of-the-wave analysis gives a catalytic rate constant of 3.6 s(-1)
      at pH 11.5 and 12 s(-1) at pH 12.5. As the electron-donating capacity at the
      aromatic ring increases, the overpotential is drastically reduced down to a
      record low of 170 mV. In addition, DFT calculations allow us to propose a
      complete catalytic cycle that uncovers an unprecedented pathway in which crucial
      O-O bond formation occurs in a two-step, one-electron process where the peroxo
      intermediate generated has no formal M-O bond but is strongly hydrogen bonded to
      the auxiliary ligand. 

PMID- 25984749
TI  - Ab Initio Comparison of Bonding Environments and Threshold Behavior in
      Ge(x)As10Se(90-x) and Ge(x)Sb10Se(90-x) Glass Models.
AB  - Ab initio models of Ge(x)As10Se(90-x), and Ge(x)Sb10Se(90-x) glasses are
      constructed, and their bonding environments are characterized and compared
      against each other and to recent experimental studies of equivalent glasses at
      the same stoichiometry and density. A minimum in the linear refractive index is
      found to correlate with a maximum in the number of length-one, predominantly Se,
      atomic chains for both glass types. The threshold behavior difference between
      GeAsSe and GeSbSe is shown to be due to the appearance of As-As-Se2 structural
      units beyond the MCN = 2.67 threshold in the GeAsSe glasses.

PMID- 25984750
TI  - Structural Investigation of (U0.7Pu0.3)O2-x Mixed Oxides.
AB  - Uranium-plutonium mixed oxide containing 30% of plutonium is a candidate fuel for
      several fast neutron and accelerator driven reactor systems. In this work, a
      detailed structural investigation on sol-gel synthesized stoichiometric
      U0.7Pu0.3O2.00 and substoichiometric U0.7Pu0.3O2-x, using X-ray diffraction
      (XRD), oxygen 17 magic angle spinning nuclear magnetic resonance ((17)O MAS NMR)
      and X-ray absorption spectroscopy is described. As observed by XRD, the
      stoichiometric U0.7Pu0.3O2.00 is monophasic with a lattice parameter in good
      agreement with Vegard's law, while the substoichiometric U0.7Pu0.3O2-x material
      is biphasic. Solid solution ideality in terms of a random distribution of metal
      atoms is proven for U0.7Pu0.3O2.00 with (17)O MAS NMR. X-ray absorption near-edge
      structure (XANES) spectroscopy shows the presence of plutonium(III) in
      U0.7Pu0.3O2-x. Extended X-ray absorption fine-structure (EXAFS) spectroscopy
      indicates a similar local structure around both cations, and comparison with XRD
      indicates a close similarity between uranium and plutonium local structures and
      the long-range ordering. 

PMID- 25984751
TI  - High-Pressure Stability of Energetic Crystal of Dihydroxylammonium 5,5'
      Bistetrazole-1,1'-diolate: Raman Spectroscopy and DFT Calculations.
AB  - The vibrational and structural behavior of a novel, energetic crystal,
      dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50), was examined over a
      broad pressure range to elucidate its structural and chemical stability at high
      pressures. Raman measurements were performed on single crystals compressed to 50
      GPa in a diamond anvil cell, and data were obtained over the entire frequency
      range of TKX-50 Raman activity. The Raman spectroscopy results were complemented
      by density functional theory (DFT) calculations to provide vibrational mode
      assignments and to gain insight into pressure effects on the vibrational and
      crystal response of TKX-50. Several features were observed in Raman spectra
      measured in the ranges 4-10, 10-13, and 32-36 GPa. We suggest that the changes
      between 32 and 36 GPa may be associated with a phase transformation. In addition,
      a number of vibrational modes showed intensity exchange and avoided crossing of
      vibrational frequency at various pressures, characteristic of the coupling of
      modes. Despite all these pressure effects, the compression of TKX-50 to 50 GPa
      and the subsequent release of pressure did not result in any irreversible
      spectral changes, demonstrating its remarkable chemical stability. DFT
      calculations, using the PBE functional with an empirical dispersion correction by
      the Grimme, PBE-D method, were used to calculate pressure effects on Raman
      frequencies and unit cell parameters. The calculated Raman shifts to 20 GPa are
      in good overall agreement with the measured shifts over a broad range of
      frequencies. The calculations also show that TKX-50 exhibits anisotropic
      compressibility, with a highly incompressible response along the a axis. The
      calculated bulk modulus, a measure of average stiffness, of TKX-50 is
      significantly higher than the calculated or measured bulk moduli of other
      energetic crystals. We suggest that the strong intermolecular interactions and
      the coupling of vibrational modes may potentially contribute to the shock
      insensitivity of TKX-50. This work demonstrates the robust high-pressure response
      of TKX-50, making this crystal attractive for practical applications. 

PMID- 25984752
TI  - Predicted pressure-induced spin and electronic transition in double perovskite
      R2CoMnO6 (R = rare-earth ion).
AB  - Specific first-principles calculations are performed to predict structural,
      magnetic and electronic properties of seven double perovskite R2CoMnO6 materials,
      with R being a rare-earth ion, under hydrostatic pressure. All these compounds
      are found to undergo a first-order transition from a high spin (HS) to low spin
      (LS) state at a critical pressure (whose value is dependent on the R ion). Such
      transition not only results in a significant volume collapse but also yields a
      dramatic change in electronic structure. More precisely, the HS-to-LS transition
      is accompanied by a transition from an insulator to a half-metallic state in the
      R2CoMnO6 compounds having the largest rare-earth ionic radius (i.e., Nd, Sm, Gd
      and Tb) while it induces a change from an insulator to a semiconductor having a
      narrow band gap for the smallest rare-earth ions (i.e., R = Dy, Ho and Er).
      Experiments are called for to confirm these predictions.

PMID- 25984753
TI  - Role of Anions Associated with the Formation and Properties of Silver Clusters.
AB  - Metal clusters have been very attractive due to their aesthetic structures and
      fascinating properties. Different from nanoparticles, each cluster of a
      macroscopic sample has a well-defined structure with identical composition, size,
      and shape. As the disadvantages of polydispersity are ruled out, informative
      structure-property relationships of metal clusters can be established. The
      formation of a high-nuclearity metal cluster involves the organization of metal
      ions into a complex entity in an ordered way. To achieve controllable preparation
      of metal clusters, it is helpful to introduce a directing agent in the formation
      process of a cluster. To this end, anion templates have been used to direct the
      formation of high nuclearity clusters. In this Account, the role of anions played
      in the formation of a variety of silver clusters has been reviewed. Silver ions
      are positively charged, so anionic species could be utilized to control the
      formation of silver clusters on the basis of electrostatic interactions, and the
      size and shape of the resulted clusters can be dictated by the templating anions.
      In addition, since the anion is an integral component in the silver clusters
      described, the physical properties of the clusters can be modulated by functional
      anions. The templating effects of simple inorganic anions and polyoxometales are
      shown in silver alkynyl clusters and silver thiolate clusters. Intercluster
      compounds are also described regarding the importance of anions in determining
      the packing of the ion pairs and making contribution to electron communications
      between the positive and negative counterparts. The role of the anions is
      threefold: (a) an anion is advantageous in stabilizing a cluster via balancing
      local positive charges of the metal cations; (b) an anion template could help
      control the size and shape of a cluster product; (c) an anion can be a key factor
      in influencing the function of a cluster through bringing in its intrinsic
      properties. Properties including electron communication, luminescent
      thermochromism, single-molecule magnet, and intercluster charge transfer
      associated with anion-directed silver clusters have been discussed. We intend to
      attract chemists' attention to the role that anions could play in determining the
      structures and properties of metal complexes, especially clusters. We hope that
      this Account will stimulate more efforts in exploiting new role of anions in
      various metal cluster systems. Anions can do much more than counterions for
      charge balance, and they should be considered in the design and synthesis of
      cluster-based functional materials. 

PMID- 25984754
TI  - Transfer of Direct and Moire Patterns by Reactive Ion Etching Through Ex Situ
      Fabricated Nanoporous Polymer Masks.
AB  - We present a conceptually simple approach to nanolithographic patterning
      utilizing ex situ fabricated nanoporous masks from block copolymers. The
      fabricated block copolymer (BC) masks show predictable morphology based on the
      correlation between BC composition and bulk properties, independent of
      substrates' surface properties. The masks are prepared by microtoming of
      prealigned nanoporous polymer monoliths of hexagonal morphology at controlled
      angles; they appear as 30-60 nm thick films of typical dimensions 100 MUm * 200
      MUm. Masks cut perpendicular to the cylindrical axis show monocrystalline
      hexagonal packing of 10 nm pores with a principal period of 20 nm. We demonstrate
      the transfer of the hexagonal pattern onto silicon by means of reactive ion
      etching through the masks. In addition, patterns of elliptic and slit-like holes
      on silicon are obtained by utilizing masks cut at 45 degrees  relative to the
      cylinder axis. Finally, we demonstrate the first transfer of moire patterns from
      block copolymer masks to substrate. The nanoporous masks prepared ex situ show
      outstanding long-range order and can be applied directly onto any flat substrate,
      eliminating the need for topographic and chemical surface modification, which are
      essential prerequisites for the conventional procedure of block copolymer
      directed self-assembly. The demonstrated elliptic and moire pattern transfers
      prove that the proposed ex situ procedure allows us to realize nanolithographic
      patterns that are difficult to realize by the conventional approach alone. 

PMID- 25984755
TI  - Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved
      Enhancement of Mutant beta-N-acetylhexosaminidase Activity.
AB  - In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6
      ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50
      value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives
      of the compound were synthesized that differ at the positions bearing the amino,
      ethyl, and chloro groups. Whereas the amino groups proved to be critical to its
      inhibitory activity, a variety of substitutions at the chloro position only
      increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with
      butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite
      its higher IC50, a derivative lacking the chlorine atom in the para-position was
      found to enhance enzyme activity in live patient cells a further 25% at
      concentrations >100 MUM, while showing less toxicity. These findings demonstrate
      the importance of the phenyl group in modulating the chaperoning efficacy and
      toxicity profile of the derivatives. 

PMID- 25984757
TI  - Facile Route to the Controlled Synthesis of Tetragonal and Orthorhombic SnO2
      Films by Mist Chemical Vapor Deposition.
AB  - Two types of tin dioxide (SnO2) films were grown by mist chemical vapor
      deposition (Mist-CVD), and their electrical properties were studied. A tetragonal
      phase is obtained when methanol is used as the solvent, while an orthorhombic
      structure is formed with acetone. The two phases of SnO2 exhibit different
      electrical properties. Tetragonal SnO2 behaves as a semiconductor, and thin-film
      transistors (TFTs) incorporating this material as the active layer exhibit n-type
      characteristics with typical field-effect mobility (MU(FE)) values of
      approximately 3-4 cm(2)/(V s). On the other hand, orthorhombic SnO2 is found to
      behave as a metal-like transparent conductive oxide. Density functional theory
      calculations reveal that orthorhombic SnO2 is more stable under oxygen-rich
      conditions, which correlates well with the experimentally observed solvent
      effects. The present study paves the way for the controlled synthesis of
      functional materials by atmospheric pressure growth techniques.

PMID- 25984756
TI  - Developing the Person-Environment Apathy Rating for persons with dementia.
AB  - OBJECTIVES: To develop the Person-Environment Apathy Rating (PEAR) scale that
      measures environmental stimulation and apathy in persons with dementia and to
      evaluate its psychometrics. METHOD: The PEAR scale consists of the PEAR
      Environment subscale and PEAR-Apathy subscales. The items were developed via
      literature review, field testing, expert review, and pilot testing. The construct
      validity and reliability were examined through video observation. The parent
      study enrolled 185 institutionalized residents with dementia. For this study, 96
      videos were selected from 24 participants. The PEAR-Environment subscale was
      validated using the Ambiance Scale and the Crowding Index. The PEAR-Apathy
      subscale was validated using the Neuropsychiatric Inventory (NPI)-Apathy,
      Passivity in Dementia Scale (PDS), and NPI-Depression. RESULTS: The PEAR
      Environment subscale and PEAR-Apathy subscales each consists of six items rated
      on a 1-4 scale. For validity, the Crowding Index slightly, yet significantly,
      correlated with the PEAR-Environment subscale total score and three of the
      individual scores. Ambiance Scale scores, both engaging and soothing, did not
      correlate with the PEAR-Environment subscale. The PEAR-Apathy highly correlated
      with the PDS and NPI-Apathy and moderately correlated with the NPI-Depression,
      suggesting good convergent validity and moderate discriminant validity. For
      reliability, both environment and apathy subscales demonstrated excellent
      internal consistency. Although facial expression and eye contact showed moderate
      inter-rater reliability, all other items showed good to excellent inter-rater and
      intra-rater reliability. CONCLUSION: This study has successfully developed the
      PEAR scale and established its psychometrics based on the compatible scales
      available. The PEAR scale is the first scale that concurrently assesses apathy
      and environmental stimulation, and is recommended for use in persons with
      dementia.

PMID- 25984758
TI  - Correction: Endothelial-derived oxidative stress drives myofibroblastic
      activation and calcification of the aortic valve.

PMID- 25984760
TI  - Asymmetric Landau bands due to spin-orbit coupling.
AB  - We show that the Landau bands obtained in a two-dimensional lateral semiconductor
      superlattice with spin-orbit coupling (SOC) of the Rashba/Dresselhaus type,
      linear in the electron momentum, placed in a tilted magnetic field, do not follow
      the symmetry of the spatial modulation. Moreover, this phenomenology is found to
      depend on the relative tilt of magnetic field and on the SOC type: (a) when only
      Rashba SOC exists and the magnetic field is tilted in the direction of the
      superlattice (b) Dresselhaus SOC exists and the magnetic field is tilted in the
      direction perpendicular to the superlattice. Consequently, measurable properties
      of the modulated system become anisotropic in a tilted magnetic field when the
      field is conically rotated around the z axis, at a fixed polar angle, as we
      demonstrate by calculating the resistivity and the magnetization. 

PMID- 25984759
TI  - The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave
      Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis.
AB  - Laser microdissection followed by mass spectrometry has been successfully used
      for amyloid typing. However, sample contamination can interfere with proteomic
      analysis, and overnight digestion limits the analytical throughput. Moreover,
      current quantitative analysis methods are based on the spectrum count, which
      ignores differences in protein length and may lead to misdiagnoses. Here, we
      developed a microwave-assisted filter-aided sample preparation (maFASP) method
      that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration
      unit and can accelerate the digestion process with the assistance of a microwave.
      Additionally, two parameters (P- and D-scores) based on the exponentially
      modified protein abundance index were developed to define the existence of
      amyloid deposits and those causative proteins with the greatest abundance. Using
      our protocol, twenty cases of systemic amyloidosis that were well-typed according
      to clinical diagnostic standards (training group) and another twenty-four cases
      without subtype diagnoses (validation group) were analyzed. Using this approach,
      sample preparation could be completed within four hours. We successfully subtyped
      100% of the cases in the training group, and the diagnostic success rate in the
      validation group was 91.7%. This maFASP-aided proteomic protocol represents an
      efficient approach for amyloid diagnosis and subtyping, particularly for serum
      contaminated samples. 

PMID- 25984761
TI  - Vapochromic luminescence and flexibility control of porous coordination polymers
      by substitution of luminescent multinuclear Cu(I) cluster nodes.
AB  - Two luminescent porous coordination polymers (PCPs), i.e., [Cu2(MU2-I)2ctpyz]n
      and [Cu4(MU3-I)4ctpyz]n (Cu2 and Cu4, respectively; ctpyz = cis-1,3,5
      cyclohexanetriyl-2,2',2"-tripyrazine), were successfully synthesized and
      characterized by single-crystal X-ray diffraction and luminescence spectroscopic
      measurements. Cu2 consists of rhombus-type dinuclear {Cu2I2} cores bridged by
      ctpyz ligands, while Cu4 is constructed of cubane-type tetranuclear {Cu4I4} cores
      bridged by ctpyz ligands. The void fraction of Cu4 is estimated to be 48.0%,
      which is significantly larger than that of Cu2 (19.9%). Under UV irradiation,
      both PCPs exhibit red luminescence at room temperature in the solid state
      (lambdaem values of 660 and 614 nm for Cu2 and Cu4, respectively). Although the
      phosphorescence of Cu2 does not change upon removal and/or adsorption of EtOH
      solvent molecules in the porous channels, the solid-state emission maximum of Cu4
      red-shifts by 36 nm (lambdaem = 650 nm) upon the removal of the adsorbed
      benzonitrile (PhCN) molecules from the porous channels (and vice versa). This
      large difference in the vapochromic behavior of Cu2 and Cu4 is closely related to
      the framework flexibility. The framework of Cu2 is sufficiently rigid to retain
      the porous structure without solvated EtOH molecules, whereas the porous
      structure of Cu4 collapses easily after removal of the adsorbed PhCN molecules to
      form a nonporous amorphous phase. The original vapor-adsorbed porous structure of
      Cu4 is regenerated by exposure of the amorphous solid to not only PhCN vapor but
      also tetrahydrofuran, acetone, ethyl acetate, and N,N-dimethylformamide vapors.
      The Cu4 structures with the various adsorbed solvents showed almost the same
      emission maxima as the original PhCN-adsorbed Cu4, except for DMF-adsorbed Cu4,
      which showed no luminescence probably because of weak coordination of the DMF
      vapor molecules to the Cu(I) centers of the tetranuclear {Cu4I4} core. 

PMID- 25984762
TI  - Correction method for line extraction in vision measurement.
AB  - Over-exposure and perspective distortion are two of the main factors underlying
      inaccurate feature extraction. First, based on Steger's method, we propose a
      method for correcting curvilinear structures (lines) extracted from over-exposed
      images. A new line model based on the Gaussian line profile is developed, and its
      description in the scale space is provided. The line position is analytically
      determined by the zero crossing of its first-order derivative, and the bias due
      to convolution with the normal Gaussian kernel function is eliminated on the
      basis of the related description. The model considers over-exposure features and
      is capable of detecting the line position in an over-exposed image. Simulations
      and experiments show that the proposed method is not significantly affected by
      the exposure level and is suitable for correcting lines extracted from an over
      exposed image. In our experiments, the corrected result is found to be more
      precise than the uncorrected result by around 45.5%. Second, we analyze
      perspective distortion, which is inevitable during line extraction owing to the
      projective camera model. The perspective distortion can be rectified on the basis
      of the bias introduced as a function of related parameters. The properties of the
      proposed model and its application to vision measurement are discussed. In
      practice, the proposed model can be adopted to correct line extraction according
      to specific requirements by employing suitable parameters. 

PMID- 25984763
TI  - Divergence of the response induced by xenogenic immunization in the sepsis
      survival of rats.
AB  - We have previously described that boosted natural xenoantibodies in rats cross
      react to bacteria by targeting carbohydrate antigens. This type of immunization
      is associated with reduced survival after cecal ligation and puncture (CLP). In
      the present study, we investigated further this phenomenon by immunizing Lewis
      rats with three intraperitoneal injections, every other day, of hamster blood
      compared to saline-injected control animals. One day after the last injection,
      CLP was performed to produce a low-grade sepsis. Induction of xenoantibodies was
      associated with a reduction in animal survival after CLP relative to controls
      (45% vs. 90%, p<0.01). No bacterial blood load was observed after CLP in this
      model either with or without xenoantibody enhancement, indicating that the
      augmented mortality was not mediated by a direct effect of boosted xenoantibodies
      over blood bacteria. Nevertheless, the xenoimmunization produced a systemic
      inflammatory response in all rats. Additionally, a lack of weight gain at the
      time of CLP was present in animals that died after the procedure, which was not
      observed in surviving rats and controls. The cytokine profile at the time of CLP
      in animals that died after the procedure was characterized by an increase in the
      serum level of several cytokines, particularly adipokines. In contrast, the
      cytokine profile at CLP of xenoimmunized rats that survived the procedure was
      characterized by a reduction in the level of cytokines. In conclusion, this study
      failed to show a direct effect of boosted xenoantibodies over blood bacterial
      isolates as cause for the decreased survival after CLP. However, it evidenced
      that non-infectious systemic inflammation may lead to a pattern of augmented
      cytokines, particularly adipokines, which impairs survival after subsequent CLP.
      Therefore, the profile of cytokines existing before the infectious insult appears
      more crucial than that resulting from the condition for the outcome of sepsis. 

PMID- 25984764
TI  - Metabolic and Gonadotropic Impact of Sequential Obesogenic Insults in the Female:
      Influence of the Loss of Ovarian Secretion.
AB  - The reproductive impact of persistent energy excess in the female remains
      incompletely defined, yet the escalating prevalence of obesity calls for better
      understanding of this phenomenon. Also along this line, the influence of ovarian
      hormones on the pathophysiology of obesity and its comorbidities merits further
      investigation. We study here the metabolic and gonadotropic impact of sequential
      obesogenic insults, namely postnatal overnutrition [by rearing in small litters
      (SL)] and high-fat diet (HFD) after weaning, in gonadal-intact and ovariectomized
      (OVX) female rats. In young (4 mo) females, SL or HFD similarly increased body
      weight, yet only a HFD evoked additional metabolic perturbations, some of which
      were worsened by precedent SL. In addition, HFD concomitantly decreased LH and
      estradiol levels and, when combined with SL, suppressed Kiss1 expression in the
      hypothalamic arcuate nucleus in 4-month females, whereas HFD up to 10-month also
      reduced LH responses to kisspeptin-10. OVX caused rapid deterioration of the
      metabolic profile, with overweight, increased energy intake, and deregulation of
      leptin and glucose/insulin levels, effects whose magnitude was similar to, if not
      higher than, HFD. Summation of previous obesogenic insults maximally increased
      body weight, basal leptin, insulin and glucose levels, and glucose intolerance.
      Yet OVX obliterated the inhibitory effects of overweight/HFD on gonadotropin
      levels and arcuate nucleus Kiss1 expression. Our study documents the deleterious
      consequences of sequential obesogenic insults on the female gonadotropin axis,
      which involve central impairment of the Kiss1 system. In addition, our work
      delineates the dramatic impact of the loss of ovarian secretions, as the
      menopausal model, on the metabolic profile of female rats, especially when
      combined with preceding obesogenic challenges. 

PMID- 25984765
TI  - Recognition of Double-Stranded DNA Using Energetically Activated Duplexes
      Modified with N2'-Pyrene-, Perylene-, or Coronene-Functionalized 2'-N-Methyl-2'
      amino-DNA Monomers.
AB  - Invader probes have been proposed as alternatives to polyamides, triplex-forming
      oligonucleotides, and peptide nucleic acids for recognition of chromosomal DNA
      targets. These double-stranded probes are activated for DNA recognition by +1
      interstrand zippers of pyrene-functionalized nucleotides. This particular motif
      forces the intercalating pyrene moieties into the same region, resulting in
      perturbation and destabilization of the probe duplex. In contrast, the two probe
      strands display very high affinity toward complementary DNA. The energy
      difference between the probe duplexes and recognition complexes provides the
      driving force for DNA recognition. In the present study, we explore the
      properties of Invader probes based on larger intercalators, i.e., perylene and
      coronene, expecting that the larger pi-surface area will result in additional
      destabilization of the probe duplex and further stabilization of probe-target
      duplexes, in effect increasing the thermodynamic driving force for DNA
      recognition. Toward this end, we developed protocols for 2'-N-methyl-2'-amino-2'
      deoxyuridine phosphoramidites that are functionalized at the N2'-position with
      pyrene, perylene, or coronene moieties and incorporated these monomers into
      oligodeoxyribonucleotides (ONs). The resulting ONs and Invader probes are
      characterized by thermal denaturation experiments, analysis of thermodynamic
      parameters, absorption and fluorescence spectroscopy, and DNA recognition
      experiments. Invader probes based on large intercalators efficiently recognize
      model targets. 

PMID- 25984766
TI  - Tuning Cooperativity on the Free Energy Landscape of Protein Folding.
AB  - Understanding the origin of the cooperativity seemingly inherent in a folding or
      unfolding reaction has been a major challenge. In particular, the relationship
      between folding cooperativity and stability is poorly understood. In this study,
      native state hydrogen exchange in conjunction with mass spectrometry has been
      used to explore the free energy landscape accessible to the small protein
      monellin, when the stability of the protein is varied. Mass distributions
      obtained in the EX1 limit of exchange have allowed a direct distinction between
      correlated (cooperative) and uncorrelated (noncooperative) structure-opening
      processes. Under conditions where the native protein is maximally stable, a
      continuum of partially unfolded states is gradually sampled before the globally
      unfolded state is transiently sampled. Under conditions that stabilize the
      unfolded state of the protein, the slowest structure-opening reactions leading to
      complete unfolding become cooperative. The present study provides experimental
      evidence for a gradual uphill unfolding transition on a very slow time scale, in
      the presence of a large free energy difference between the native and unfolded
      states. The results suggest that the cooperativity that manifests itself in
      protein folding and unfolding reactions carried out in the presence of denaturant
      might merely be a consequence of the effect of the denaturant on the unfolded
      state and transition state stabilities. 

PMID- 25984767
TI  - Creation of transgenic rice plants producing small interfering RNA of Rice tungro
      spherical virus.
AB  - Rice tungro spherical virus (RTSV), also known as Rice waika virus, does not
      cause visible symptoms in infected rice plants. However, the virus plays a
      critical role in spreading Rice tungro bacilliform virus (RTBV), which is the
      major cause of severe symptoms of rice tungro disease. Recent studies showed that
      RNA interference (RNAi) can be used to develop virus-resistance transgenic rice
      plants. In this report, we presented simple procedures and protocols needed for
      the creation of transgenic rice plants capable of producing small interfering RNA
      specific against RTSV sequences. Notably, our study showed that 60 out of 64
      individual hygromycin-resistant lines (putative transgenic lines) obtained
      through transformation carried transgenes designed for producing hairpin double
      stranded RNA. Northern blot analyses revealed the presence of small interfering
      RNA of 21- to 24-mer in 46 out of 56 confirmed transgenic lines. Taken together,
      our study indicated that transgenic rice plants carrying an inverted repeat of
      500-bp fragments encoding various proteins of RTSV can produce small interfering
      RNA from the hairpin RNA transcribed from that transgene. In light of recent
      studies with other viruses, it is possible that some of these transgenic rice
      lines might be resistant to RTSV.

PMID- 25984768
TI  - Expression of synthetic human tropoelastin (hTE) protein in Nicotiana tabacum.
AB  - Plant molecular farming (PMF) is an important growing prospective approach in
      plant biotechnology; it includes production of recombinant pharmaceutical and
      industrial proteins in large quantities from engineered plants. Elastin is a
      major protein component of tissues that require elasticity, it helps keep skin
      smooth as it stretches to allow normal. Elastin is used as a raw material for the
      cosmetic industry. In this work, we aimed to use plant as a bioreactor for the
      expression and production of the full human tropoelastin protein. Agrobacterium-
      mediated transient expression system into Nicotiana tabacum using syringe
      agroinfiltration was used to provide fast and convenient way to produce
      recombinant proteins with greater expression overall the plant leaf. This study
      aimed to establish an efficient and rapid system for transiently expression and
      production of human recombinant tropoelastin protein in transgenic N. tabacum
      plants. Modified elastin (ELN) gene was biosynthesized and cloned into
      pCambia1390 vector to be used into N. tabacum agroinfilteration. Optimization of
      codon usage for the human tropoelastin gene, without changing the primary
      structure of the protein was carried out to ensure high expression in tobacco
      plants. The obtained data proved that the 5(th) day post-infiltration is the
      optimum interval to obtain the maximum production of our recombinant protein.
      Southern blot analysis was able to detect 2175 bp fragment length representing
      the ELN orf (open reding frame). On the other hand, ELN -expression within
      plant's tissue was visualized by RT-PCR during the period 3-10 days post
      agroinfiltration. At the protein level, western and ELISA confirmed the
      expression of recombinant tropoelastin protein. Western blot analysis detected
      the tropoelastin protein as parent band at ~70 kDa from freshly extracted
      protein, while two degraded bands of ~55 and ~45 kDa, representing a pattern of
      tropoelastin were appeared with frozen samples. This study showed that
      biosynthetic ELN gene was successfully expressed into N. tabacum leaves using
      agroinfiltration technique.

PMID- 25984769
TI  - pH-Dependent Liquid-Liquid Phase Separation of Highly Supersaturated Solutions of
      Weakly Basic Drugs.
AB  - Supersaturated solutions of poorly aqueous soluble drugs can be formed both in
      vivo and in vitro. For example, increases in pH during gastrointestinal transit
      can decrease the aqueous solubility of weakly basic drugs resulting in
      supersaturation, in particular when exiting the acidic stomach environment.
      Recently, it has been observed that highly supersaturated solutions of drugs with
      low aqueous solubility can undergo liquid-liquid phase separation (LLPS) prior to
      crystallization, forming a turbid solution such that the concentration of the
      drug in the continuous solution phase corresponds to the amorphous solubility
      while the colloidal phase is composed of a disordered drug-rich phase. Although
      it is well established that the equilibrium solubility of crystalline weakly
      basic drugs follows the Henderson-Hasselbalch relationship, the impact of pH on
      the LLPS phenomenon or the amorphous solubility has not been explored. In this
      work, the LLPS concentration of three weakly basic compounds-clotrimazole,
      nicardipine, and atazanavir-was determined as a function of pH using three
      different methods and was compared to the predicted amorphous solubility, which
      was calculated from the pH-dependent crystalline solubility and by estimating the
      free energy difference between the amorphous and crystalline forms. It was
      observed that, similar to crystalline solubility, the experimental amorphous
      solubility at any pH follows the Henderson-Hasselbalch relation and can be
      predicted if the amorphous solubility of the free base is known. Excellent
      agreement between the LLPS concentration and the predicted amorphous solubility
      was observed. Dissolution studies of amorphous drugs showed that the solution
      concentration can reach the corresponding LLPS concentration at that pH. Solid
      state analysis of the precipitated material confirmed the amorphous nature. This
      work provides insight into the pH-dependent precipitation behavior of poorly
      water-soluble compounds and provides a fundamental basis with which to understand
      the performance of supersaturating dosage forms. 

PMID- 25984770
TI  - PATHOGENESIS AND IMMUNE RESPONSES OF FRANCISELLA TULARENSIS STRAINS IN WILD
      CAUGHT COTTONTAIL RABBITS (SYLVILAGUS SPP.).
AB  - Francisella tularensis is a highly virulent, zoonotic bacterium that causes
      significant natural disease and is of concern as an organism for bioterrorism.
      Serologic testing of wildlife is frequently used to monitor spatial patterns of
      infection and to quantify exposure. Cottontail rabbits (Sylvilagus spp.) are a
      natural reservoir for F. tularensis in the US, although very little work has been
      done experimentally to determine how these animals respond to infection; thus,
      information gathered from field samples can be difficult to interpret. We
      characterized clinical disease, bacteremia, pathology, and antibody kinetics of
      North American cottontail rabbits experimentally infected with five strains of F.
      tularensis. Rabbits were infected with four field strains, including MA00-2987
      (type A1b), WY96-3418 (type A2), KY99-3387, and OR96-0246 (type B), and with
      SchuS4 (type A1a), a widely used, virulent laboratory strain. Infection with the
      different strains of the bacterium resulted in varied patterns of clinical
      disease, gross pathology, and histopathology. Each of the type A strains were
      highly virulent, with rabbits succumbing to infection 3-13 d after infection. At
      necropsy, numerous microabscesses were observed in the livers and spleens of most
      rabbits, associated with high bacterial organ burdens. In contrast, most rabbits
      infected with type B strains developed mild fever and became lethargic, but the
      disease was infrequently lethal. Those rabbits infected with type B strains that
      survived past 14 d developed a robust humoral immune response, and F. tularensis
      was not isolated from liver, spleen, or lung of those animals. Understanding F.
      tularensis infection in a natural reservoir species can guide serosurveillance
      and generate new insights into environmental maintenance of this pathogen. 

PMID- 25984771
TI  - Comparison of Buffered, Acidified Plate Antigen to Standard Serologic Tests for
      the Detection of Serum Antibodies to Brucella abortus in Elk (Cervus canadensis).
AB  - Brucellosis (caused by the bacterium Brucella abortus) is a zoonotic disease
      endemic in wild elk (Cervus canadensis) of the Greater Yellowstone Ecosystem, US.
      Because livestock and humans working with elk or livestock are at risk, validated
      tests to detect the B. abortus antibody in elk are needed. Using the kappa
      statistic, we evaluated the buffered, acidified plate antigen (BAPA) assay for
      agreement with the results of the four serologic tests (card test [card],
      complement fixation test [CF], rivanol precipitation plate agglutination test
      [RIV], standard plate agglutination test [SPT]) that are approved by the US
      Department of Agriculture for the detection of the B. abortus antibody in elk.
      From 2006 to 2010, serum samples collected from elk within B. abortus-endemic
      areas (n = 604) and nonendemic areas (n = 707) and from elk culture-positive for
      B. abortus (n = 36) were split and blind tested by four elk serum diagnostic
      laboratories. kappa-Values showed a high degree of agreement for the card
      (0.876), RIV (0.84), and CF (0.774) test pairings and moderate agreement for the
      SPT (0.578). Sensitivities for the BAPA, card, RIV, CF, and SPT were 0.859,
      0.839, 0.899, 1.00, and 0.813, whereas specificities were 0.986, 0.993, 0.986,
      0.98, and 0.968, respectively. The positive predictive values and the negative
      predictive values were calculated for 2.6%, 8.8%, and 16.2% prevalence levels.
      These findings suggest the BAPA test is a suitable screening test for the B.
      abortus antibodies in elk.

PMID- 25984772
TI  - POTENTIAL FOR GREAT EGRETS (ARDEA ALBA) TO TRANSMIT A VIRULENT STRAIN OF
      AEROMONAS HYDROPHILA AMONG CHANNEL CATFISH (ICTALURUS PUNCTATUS) CULTURE PONDS.
AB  - Aeromonas hydrophila is a gram-negative, rod-shaped, facultative, anaerobic
      bacterium that is ubiquitous in freshwater and slightly brackish aquatic
      environments and infects fish, humans, reptiles, and birds. Recent severe
      outbreaks of disease in commercial channel catfish (Ictalurus punctatus)
      aquaculture ponds have been associated with a highly virulent A. hydrophila
      strain (VAH), which is genetically distinct from less-virulent strains. The
      epidemiology of this disease has not been determined. Given that A. hydrophila
      infects birds, we hypothesized that fish-eating birds may serve as a reservoir
      for VAH and spread the pathogen by flying to uninfected ponds. Great Egrets
      (Ardea alba) were used in this transmission model because these wading birds
      frequently prey on farmed catfish. Great Egrets that were fed VAH-infected
      catfish shed VAH in feces demonstrating their potential to spread VAH. 

PMID- 25984773
TI  - PARASITOLOGY AND SEROLOGY OF FREE-RANGING COYOTES (CANIS LATRANS) IN NORTH
      CAROLINA, USA.
AB  - Coyotes (Canis latrans) have expanded recently into the eastern US and can serve
      as a source of pathogens to domestic dogs (Canis lupus familiaris), livestock,
      and humans. We examined free-ranging coyotes from central North Carolina, US, for
      selected parasites and prevalence of antibodies against viral and bacterial
      agents. We detected ticks on most (81%) coyotes, with Amblyomma americanum
      detected on 83% of those with ticks. Fifteen (47%) coyotes were positive for
      heartworms (Dirofilaria immitis), with a greater detection rate in adults (75%)
      than juveniles (22%). Serology revealed antibodies against canine adenovirus
      (71%), canine coronavirus (32%), canine distemper virus (17%), canine parvovirus
      (96%), and Leptospira spp. (7%). We did not detect antibodies against Brucella
      abortus/suis or Brucella canis. Our results showed that coyotes harbor many
      common pathogens that present health risks to humans and domestic animals and
      suggest that continued monitoring of the coyote's role in pathogen transmission
      is warranted. 

PMID- 25984774
TI  - EPIZOOTIOLOGY OF CRANIAL ABSCESS DISEASE IN WHITE-TAILED DEER (ODOCOILEUS
      VIRGINIANUS) OF GEORGIA, USA.
AB  - Intracranial abscess disease is a cause of natural mortality for mature male
      white-tailed deer (Odocoileus virginianus). Most cases of abscesses are
      associated with bacterial infection by Trueperella (Arcanobacterium) pyogenes,
      but a complete understanding of the epidemiology of this disease is lacking. We
      quantified the effects of individual characteristics, site-specific herd
      demographics, land cover, and soil variables in estimating the probability of
      this disease. We examined 7,545 white-tailed deer from 60 sites throughout
      Georgia US for signs of cranial abscesses, the predecessor of intracranial
      abscesses, and recorded the presence or absence of cranial abscesses for each
      individual examined. We detected no cranial abscesses in 2,562 female deer but 91
      abscesses in 4,983 male deer examined (1.8%). A generalized linear mixed model,
      treating site as a random effect, was used to examine several potential
      explanatory risk factors including site-level landscape and soil characteristics
      (soil and forest type), demographic factors (deer density and male to female
      ratio), and individual host factors (deer sex and age). Model results indicated
      that the probability of a male having a cranial abscess increased with age and
      that adult sex ratio (male:female) was positively associated with this disease.
      Site-specific variables for land cover and soil types were not strongly
      associated with observations of the disease at the scale measured and a large
      amount of among-site variability remained. Given the demonstrated effect of age,
      gender, and local sex ratios but the remaining unexplained spatial variability,
      additional investigation into spatiotemporal variation of the presumed bacterial
      causative agent of cranial abscesses appears warranted. 

PMID- 25984775
TI  - Amplatzer Device in Bronchial Stump Fistula after Extrapleural Pneumonectomy.
AB  - Endoscopically superimposed Amplatzer (St. Jude Medical, St. Paul, Minnesota,
      United States) septal occluder plug was successfully used in the treatment of
      septic right main bronchus fistula having developed after extrapleural
      pneumonectomy and heated chemotherapy in two patients with malignant pleural
      mesothelioma. In the first case the method was curative and in the other
      Amplatzer served as temporary bridging allowing rehabilitation from empyema and
      sepsis. After 4.5 and 4.2 years both patients are alive with no sign of relapse
      of mesothelioma or infection. 

PMID- 25984776
TI  - Achievements of Unilateral Sympathectomy.

PMID- 25984777
TI  - Is Single Level Paravertebral Analgesia Enough for Controlling Postoperative Pain
      in VATS?

PMID- 25984778
TI  - Endobronchial Treatment of Carcinoid Tumors of the Lung.
AB  - BACKGROUND: Bronchial carcinoid tumors are known as low-grade malignancies.
      Surgery has been proposed as the best treatment of choice for lung carcinoids.
      However, less invasive treatment approaches may be considered due to low-grade
      malignancy potential of such tumors. The aim of this study was to review the
      results of endobronchial treatments of carcinoid tumors of the lung and to
      compare with the outcome after surgery. METHODS: Initial complete tumor
      eradication with an endobronchial treatment was attempted for 29 patients. Diode
      laser or argon plasma coagulation was used during these treatments. Cryotherapy
      or laser treatments were applied consecutively in patients for whom there was
      good bronchoscopic visualization of the distal and basal tumor margins and no
      evidence of bronchial wall involvement. Surgery was performed in cases of
      atypical carcinoid and in cases of nonvisualization of the basal and distal part
      of the tumor. RESULTS: Overall, 29 patients have been included (median age 58
      years; range, 23-77 years). Median follow-up has been 49 months (range, 22-94
      months). A total of 24 patients (69%) had typical carcinoid tumor, 5 patients
      (31%) had atypical carcinoid tumor. Initial endobronchial treatment provided
      complete tumor eradication in 21 of 29 patients (72%). Of the eight other
      patients (28%), two were atypical carcinoids, and underwent surgical treatment.
      There was no tumor-related death and no recurrence during the follow-up in both
      groups. There was no difference for survival or recurrence between the surgical
      and the endobronchial treatment group of patients (p > 0.05). CONCLUSION:
      Endobronchial treatment may be considered as safe, effective treatment for
      typical carcinoid tumors in the central airways. Addition of initial
      endobronchial treatment had no negative effect on the surgical outcome.

PMID- 25984779
TI  - Electrocautery versus Ultracision versus LigaSure in Surgical Management of
      Hyperhidrosis.
AB  - OBJECTIVE: The aim of the study was to evaluate the sympathectomy procedures for
      primary hyperhidrosis in terms of complications and effectiveness. METHODS: From
      January 2010 to September 2012 we performed 130 sympathectomies in 65 patients,
      27 males (42%) and 38 females (58%). Electrocoagulation was used in 20 procedures
      (15%), ultrasonic scalpel in 54 (42%), and radiofrequency dissector in 56 (43%).
      Seven patients (11%) underwent bilateral sympathectomy in the same surgical
      session, while in 58 (89%) the right surgical approach was delayed 30 days from
      the first procedure. RESULTS: We noticed 12 complications (9%): (a) chest pain in
      6 patients (4 with electrocoagulation, 1 with ultrasonic scalpel, and 1 with
      radiofrequency dissector), which disappeared in 20 +/- 1 day; (b) paresthesias in
      3 electrocoagulation patients, was solved in 23 +/- 5 days; (c) bradycardia in 1
      ultrasonic patient, normalized in 4th postoperative hour; (d) unilateral relapse
      in 2 electrocoagulation patients after the second side approach, positively
      treated in 1 patient by resurgery in video-assisted thoracoscopy (VAT). The
      quality-adjusted life year and the quality of life evaluation revealed a
      statistically significant improvement (p = 0.02) in excessive sweating and
      general satisfaction after surgery, with Ultracision and LigaSure showing better
      findings than electrocoagulation. CONCLUSION: The latest generation devices
      offered greater efficacy in the treatment of hyperhidrosis, minimizing
      complications and facilitating the resumption of normal work and social activity
      of patients.

PMID- 25984780
TI  - Racial and Ethnic Differences in Lung Cancer Surgical Stage: An STS Database
      Study.
AB  - BACKGROUND: Racial and ethnic differences in lung cancer care have been
      previously documented. These differences may be related to access to care,
      cultural differences, or fewer patients presenting with operable lung cancer. The
      relationship between race and pathologic stage of patients who undergo lung
      cancer resection has not been defined. This study estimates racial disparities in
      lung cancer stage among patients who undergo surgical resection. METHODS: The
      Society of Thoracic Surgeons (STS) database was queried for patients who
      underwent resection of non-small cell lung cancer and had complete pathologic
      staging and racial identification. Univariate and multivariate analyses were
      performed. Study end point was the pathologic stage and we evaluated its
      association with the racial and ethnic origins of the patients. RESULTS: Of
      19,173 eligible patients with non-small cell lung cancer of known pathological
      stage who underwent surgery between 2002 and 2008, the majority were Caucasian
      (17,148, 89.4%), 1,502 (7.8%) were African-American, 273 (1.4%) were Asian, and
      250 (1.3%) were Hispanic. In univariate analysis, significantly more Caucasian
      and African-American patients underwent resection of stage I/II lung cancer
      (13,929, 81.2% and 1,217, 81%, respectively) as compared with the Asian (207,
      75.2%) and Hispanic (188, 75.8%) patients (p = 0.007). Stage at operation did not
      differ between Caucasians and African-Americans. Multivariate analysis confirmed
      these findings (p = 0.03) after adjustment for age, gender, tobacco use,
      diabetes, and year of surgery. CONCLUSION: Within the STS database, patients
      identified as Asian or Hispanic had a significantly higher pathologic stage at
      the time of resection than Caucasian or African-American patients. The causes of
      these differences in the treatment of potentially curable lung cancer are unknown
      and require further investigation.

PMID- 25984781
TI  - Reply by the Authors of the Original Article.

PMID- 25984782
TI  - Correction: Parasite Prevalence Corresponds to Host Life History in a Diverse
      Assemblage of Afrotropical Birds and Haemosporidian Parasites.

PMID- 25984783
TI  - Alcohol-related emergency department admissions among adolescents in the Ghent
      and Sint-Niklaas areas.
AB  - Alcohol abuse is a major health concern. The aim of this retrospective study was
      to analyse the alcohol-related emergency department (ED) admissions among
      adolescents in all hospitals of distinct areas during a 1-year period. In each
      hospital, all ED patients with a blood alcohol concentration (BAC) of at least
      0.5 g/l were surveyed in a standardised way. Of the 3918 included patients, only
      146 (3.7%) were < 18  years. The male-to-female ratio was 1.5:1. There was a
      strong preponderance of weekend and night time admissions. Most of the patients
      were transported by ambulance (77% of 138 patients with information on this
      item). The main reason for ED admittance was depressed level of consciousness
      (64%), trauma (12%), vomiting and/or abdominal pain (12%), agitation or
      aggression (4%), syncope (4%) and psychological problems (4%). The context of the
      alcohol intoxication was related to some kind of festivity in 85%, mental
      problems in 14% and chronic abuse in 1%. Median BAC values (and range) were 2.08
      g/l (0.73-3.70 g/l) for boys and 1.51 g/l (0.73-2.90 g/l) for girls. Most
      patients (87%) could be discharged home within 24  hours. Our study confirms that
      problematic alcohol use leading to ED admissions starts in adolescence. Although
      the numbers of cases below 18 years are low when compared to adults, the
      phenomenon is alarming as it is associated with substantial health problems.
      Therefore, Belgium urgently needs a global national alcohol plan, with youngsters
      being one of the target groups.

PMID- 25984784
TI  - [Epidemiology of hip fractures and its social and economic impact. An update for
      2014].
AB  - Hip fractures (HF) following low-impact trauma are the most visible and dramatic
      consequences of osteoporosis (OP). It is estimated that within one year after HF,
      20 to 30% of the patients die, 50-60% become disabled and only 30-40% fully
      recover their previous functional levels. Therefore, its medical, societal and
      economic impact is huge and it is not fully delivered by the event itself, but
      rather by its consequences. This paper aims to update data published by Branco et
      al. 2009 about epidemiology and burden of HF, specifically to revise the national
      data. In Portugal there have been 77,083 HF reported between 2000 and 2008 with
      increasing numbers with ageing along with due associated refracture and mortality
      rates. Recent results suggest a slight change at clinical level concerning the
      pharmacological approach for the treatment of HF, however it is still important
      to stay alert to the patients' needs and to their bone mineral density losses in
      order to avoid repeating the occurrence of these events, aiming to generate
      significant benefits in terms of health outcomes and due public expenditure. 

PMID- 25984785
TI  - Saying "no" to temptation: Want-to motivation improves self-regulation by
      reducing temptation rather than by increasing self-control.
AB  - Self-regulation has been conceptualized as the interplay between controlled and
      impulsive processes; however, most research has focused on the controlled side
      (i.e., effortful self-control). The present studies focus on the effects of
      motivation on impulsive processes, including automatic preferences for goal
      disruptive stimuli and subjective reports of temptations and obstacles,
      contrasting them with effects on controlled processes. This is done by examining
      people's implicit affective reactions in the face of goal-disruptive
      "temptations" (Studies 1 and 2), subjective reports of obstacles (Studies 2 and
      3) and expended effort (Study 3), as well as experiences of desires and self
      control in real-time using experience sampling (Study 4). Across these multiple
      methods, results show that want-to motivation results in decreased impulsive
      attraction to goal-disruptive temptations and is related to encountering fewer
      obstacles in the process of goal pursuit. This, in turn, explains why want-to
      goals are more likely to be attained. Have-to motivation, on the other hand, was
      unrelated to people's automatic reactions to temptation cues but related to
      greater subjective perceptions of obstacles and tempting desires. The discussion
      focuses on the implications of these findings for self-regulation and motivation.

PMID- 25984786
TI  - Directed abstraction: Encouraging broad, personal generalizations following a
      success experience.
AB  - People with negative self-views may fail to generalize appropriately from success
      experiences (e.g., Wood, Heimpel, Newby-Clark, & Ross, 2005). We drew on theories
      regarding self-views (Swann, Griffin, Predmore, & Gaines, 1987) and abstraction
      (Semin & Fiedler, 1991), as well as past linguistic framing work (e.g., Marigold,
      Holmes, & Ross, 2007, 2010; Salancik, 1974), to create a new technique to
      encourage people with negative self-views to generalize broadly from a success
      experience to the self-concept. We call this technique directed abstraction. In
      Experiment 1, participants with negative self-views who completed a directed
      abstraction writing task following success feedback regarding a novel laboratory
      task generalized more from that success, reporting higher ability levels and
      greater expectations of future success in the relevant domain. In Experiment 2,
      directed abstraction produced similar results (including more positive self
      related affect, e.g., pride) after participants recalled a past public speaking
      success. In Experiment 3, participants high in fear of public speaking gave two
      speeches in a context designed to be challenging yet also to elicit successful
      performances. Directed abstraction helped these participants generalize from
      their success to beliefs about their abilities, expectations about the future,
      and confidence as a speaker. In Experiment 4, directed abstraction following
      success on a verbal task increased persistence in the face of failure on a
      subsequent verbal task. We discuss implications for understanding how and when
      people generalize from a success, compare directed abstraction to existing
      interventions, and suggest practical applications for this influence technique.

PMID- 25984787
TI  - Put your plan into action: The influence of action plans on agency and
      responsibility.
AB  - While action plans and intentions have been considered to be important factors
      contributing to the personal sense of causation known as agency, the present
      research is the first to empirically investigate how action plans influence
      agency. Participants in multiple studies were required to plan or not to plan
      ahead their actions. Results consistently show that on trials in which
      participants were required to plan their actions, participants experienced
      reduced agency compared to trials in which participants were not required to plan
      their actions. These results were found for both explicit agency paradigms in
      which participants were asked for their experiences of causation (Studies 1 and
      2), as well as in an implicit agency paradigm in which participants were asked to
      estimate the time between their actions and the consequences of their actions
      (Study 3). In addition, it was shown that the reduction in agency was smaller
      when plans and actions were temporally closer together (Study 4). In a final line
      of experiments we discovered that prior planning similarly reduced both the
      emotional experience of acting and feelings of responsibility in agents (Studies
      5-7). However, the direction of this effect was reversed in observers, for whom
      cues related to planning by others increased attributions of responsibility
      toward those others (Study 8).

PMID- 25984788
TI  - Awe, the small self, and prosocial behavior.
AB  - Awe is an emotional response to perceptually vast stimuli that transcend current
      frames of reference. Guided by conceptual analyses of awe as a collective
      emotion, across 5 studies (N = 2,078) we tested the hypothesis that awe can
      result in a diminishment of the individual self and its concerns, and increase
      prosocial behavior. In a representative national sample (Study 1), dispositional
      tendencies to experience awe predicted greater generosity in an economic game
      above and beyond other prosocial emotions (e.g., compassion). In follow-up
      experiments, inductions of awe (relative to various control states) increased
      ethical decision-making (Study 2), generosity (Study 3), and prosocial values
      (Study 4). Finally, a naturalistic induction of awe in which participants stood
      in a grove of towering trees enhanced prosocial helping behavior and decreased
      entitlement compared to participants in a control condition (Study 5).
      Mediational data demonstrate that the effects of awe on prosociality are
      explained, in part, by feelings of a small self. These findings indicate that awe
      may help situate individuals within broader social contexts and enhance
      collective concern.

PMID- 25984789
TI  - Living with limited time: Socioemotional selectivity theory in the context of
      health adversity.
AB  - The current research was designed to test the applicability of socioemotional
      selectivity theory (SST; Carstensen, 2006), a life span theory that posits that
      perceived time remaining in life (time perspective) is a critical determinant of
      motivation, to individuals who face foreshortened futures (limited time
      perspective) due to life-limiting medical illness. In Study 1, we investigated
      whether life goals and biases in attention and memory for valenced emotional
      stimuli differed between women living with metastatic breast cancer (n = 113;
      theoretically living under greater limited time perspective than peers without
      cancer) and similarly aged women without a cancer diagnosis (n = 50;
      theoretically living under greater expansive time perspective than peers with
      cancer) in accordance with SST. As hypothesized, metastatic group goals reflected
      greater emphasis on limited versus expansive time perspective relative to
      comparison group goals. Hypotheses regarding biases in attention and memory were
      not supported. Study 2 followed metastatic group participants over 3 months and
      revealed that, consistent with hypotheses, whereas limited time perspective goals
      predicted decreased intrusive thoughts about cancer, expansive time perspective
      goals predicted decreased perceived cancer-related benefits. Together, these
      studies suggest that SST is a useful lens through which to view some components
      of motivation and psychological adjustment among individuals confronting
      medically foreshortened futures.

PMID- 25984790
TI  - Recalibration and validation of the Charlson comorbidity index in Korean incident
      hemodialysis patients.
AB  - BACKGROUND: Weights assigned to comorbidities to predict mortality may vary based
      on the type of index disease and advances in the management of comorbidities. We
      aimed to develop a modified Charlson comorbidity index (CCI) in incident
      hemodialysis patients (mCCI-IHD), thereby improving risk stratification for
      mortality. METHODS: Data on 24,738 Koreans who received their first hemodialysis
      treatment between 2005 and 2008 were obtained from the Korean Health Insurance
      dataset. The mCCI-IHD score were calculated by summing up the weights which were
      assigned to individual comorbidities according to their relative prognostic
      significance determined by multivariate Cox proportional hazards model. The
      modified index was validated in an independent nationwide prospective cohort
      (n=1,100). RESULTS: The Cox proportional hazards model revealed that all
      comorbidities in the CCI except ulcers significantly predicted mortality. Thus,
      the mCCI-IHD included 14 comorbidities with re-assigned severity weights. In the
      validation cohort, both the CCI and the mCCI-IHD were correlated with mortality.
      However, the mCCI-IHD showed modest but significant increases in c statistics
      compared with the CCI at 6 months and 1 year. The analyses using continuous net
      reclassification improvement revealed that the mCCI-IHD improved net mortality
      risk reclassification by 24.6% (95% CI, 2.5-46.7; P=0.03), 26.2% (95% CI, 1.0
      51.4; P=0.04) and 42.8% (95% CI, 4.9-80.8; P=0.03) with respect to the CCI at 6
      months and 1 and 2 years, respectively. CONCLUSIONS: The mCCI-IHD facilitates
      better risk stratification for mortality in incident hemodialysis patients
      compared with the CCI, suggesting that it may be a preferred index for use in
      clinical practice and the statistical analysis of epidemiological studies.

PMID- 25984791
TI  - Heterogeneity of prognostic studies of 24-hour blood pressure variability:
      systematic review and meta-analysis.
AB  - In addition to mean blood pressure, blood pressure variability is hypothesized to
      have important prognostic value in evaluating cardiovascular risk. We aimed to
      assess the prognostic value of blood pressure variability within 24 hours. Using
      MEDLINE, EMBASE and Cochrane Library to April 2013, we conducted a systematic
      review of prospective studies of adults, with at least one year follow-up and any
      day, night or 24-hour blood pressure variability measure as a predictor of one or
      more of the following outcomes: all-cause mortality, cardiovascular mortality,
      all cardiovascular events, stroke and coronary heart disease. We examined how
      blood pressure variability is defined and how its prognostic use is reported. We
      analysed relative risks adjusted for covariates including the appropriate mean
      blood pressure and considered the potential for meta-analysis. Our analysis of
      methods included 24 studies and analysis of predictions included 16 studies.
      There were 36 different measures of blood pressure variability and 13 definitions
      of night- and day-time periods. Median follow-up was 5.5 years (interquartile
      range 4.2-7.0). Comparing measures of dispersion, coefficient of variation was
      less well researched than standard deviation. Night dipping based on percentage
      change was the most researched measure and the only measure for which data could
      be meaningfully pooled. Night dipping or lower night-time blood pressure was
      associated with lower risk of cardiovascular events. The interpretation and use
      in clinical practice of 24-hour blood pressure variability, as an important
      prognostic indicator of cardiovascular events, is hampered by insufficient
      evidence and divergent methodologies. We recommend greater standardisation of
      methods. 

PMID- 25984793
TI  - Novel loci for non-syndromic coarctation of the aorta in sporadic and familial
      cases.
AB  - BACKGROUND: Coarctation of the aorta (CoA) accounts for 5-8% of all congenital
      heart defects. CoA can be detected in up to 20% of patients with Ullrich-Turner
      syndrome (UTS), in which a part or all of one of the X chromosomes is absent. The
      etiology of non-syndromic CoA is poorly understood. In the present work, we test
      the hypothesis that rare copy number variation (CNV) especially on the gonosomes,
      contribute to the etiology of non-syndromic CoA. METHODS: We performed high
      resolution genome-wide CNV analysis using the Affymetrix SNP 6.0 microarray
      platform for 70 individuals with sporadic CoA, 3 families with inherited CoA
      (n=13) and 605 controls. Our analysis comprised genome wide association, CNV
      burden and linkage. CNV was validated by multiplex ligation-dependent probe
      amplification. RESULTS: We identified a significant abundance of large (>100 kb)
      CNVs on the X chromosome in males with CoA (p=0.005). 11 out of 51 (~ 22%) male
      cases had these large CNVs. Association analysis in the sporadic cohort revealed
      14 novel loci for CoA. The locus on 21q22.3 in the sporadic CoA cohort overlapped
      with a gene locus identified in all familial cases of CoA (candidate gene TRPM2).
      We identified one CNV locus within a locus with high multipoint LOD score from a
      linkage analysis of the familial cases (SEPT9); another locus overlapped with a
      region implicated in Kabuki syndrome. In the familial cases, we identified a
      total of 7 CNV loci that were exclusively present in cases but not in unaffected
      family members. CONCLUSION: Of all candidate loci identified, the TRPM2 locus was
      the most frequently implicated autosomal locus in sporadic and familial cases.
      However, the abundance of large CNVs on the X chromosome of affected males
      suggests that gonosomal aberrations are not only responsible for syndromic CoA
      but also involved in the development of sporadic and non-syndromic CoA and their
      male dominance.

PMID- 25984795
TI  - Enzymatic Catalysis Combining the Breath Figures and Layer-by-Layer Techniques:
      Toward the Design of Microreactors.
AB  - Herein, we report the fabrication of microstructured porous surfaces with
      controlled enzymatic activity by combining the breath figures and the layer-by
      layer techniques. Two different types of porous surfaces were designed based on
      fluorinated and carboxylated copolymers in combination with PS, using
      poly(2,3,4,5,6-pentafluorostyrene)-b-polystyrene (PS5F31-b-PS21) and polystyrene
      b-poly(acrylic acid) (PS19-b-PAA10) block copolymers, respectively. For
      comparative purposes, flat surfaces having similar chemistry were obtained by
      spin-coating. Poly(sodium 4-styrenesulfonate)/poly(allylamine hydrochloride)
      (PSS/PAH) multilayers incorporating alkaline phosphatase (ALP) were built on
      these porous surfaces to localize the enzyme both inside and outside of the pores
      using PS/PS5F31-b-PS21 surfaces and only inside the pores on PS/PS19-b-PAA10
      surfaces. A higher catalytic activity of ALP (about three times) was obtained
      with porous surfaces compared to the flat ones. The catalysis happens
      specifically inside the holes of PS/PS19-b-PAA10surfaces, where ALP is located.
      This opens the route for applications in microreactors. 

PMID- 25984792
TI  - Associations of Erythrocyte Fatty Acids in the De Novo Lipogenesis Pathway with
      Proxies of Liver Fat Accumulation in the EPIC-Potsdam Study.
AB  - BACKGROUND: Biomarker fatty acids (FAs) reflecting de novo lipogenesis (DNL) are
      strongly linked to the risk of cardiometabolic diseases. Liver fat accumulation
      could mediate this relation. There is very limited data from human population
      based studies that have examined this relation. OBJECTIVE: The aim of this study
      was to investigate the relation between specific FAs in the DNL pathway and liver
      fat accumulation in a large population-based study. METHODS: We conducted a cross
      sectional analysis of a subsample (n = 1,562) of the EPIC-Potsdam study, which
      involves 27,548 middle-aged men and women. Baseline blood samples have been
      analyzed for proportions of 32 FAs in erythrocyte membranes (determined by gas
      chromatography) and biomarker concentrations in plasma. As indicators for DNL,
      the DNL-index (16:0 / 18:2n-6) and proportions of individual blood FAs in the DNL
      pathway were used. Plasma parameters associated with liver fat content (fetuin-A,
      ALT, and GGT) and the algorithm-based fatty liver index (FLI) were used to
      reflect liver fat accumulation. RESULTS: The DNL-index tended to be positively
      associated with the FLI and was positively associated with GGT activity in men (p
      for trend: 0.12 and 0.003). Proportions of 14:0 and 16:0 in erythrocytes were
      positively associated with fetuin-A, whereas 16:1n-7 were positively associated
      with the FLI and GGT activity (all p for trends in both sexes at least 0.004).
      Furthermore, the proportion of 16:1n-7 was positively related to fetuin-A in
      women and ALT activity in men (all p for trend at least 0.03). The proportion of
      16:1n-9 showed positive associations with the FLI and GGT activity in men and
      fetuin-A in both sexes, whereas 18:1n-7 was positively associated with GGT
      activity in men (all p for trend at least 0.048). CONCLUSION: Findings from this
      large epidemiological study suggest that liver fat accumulation could link
      erythrocyte FAs in the DNL pathway to the risk of cardiometabolic diseases.

PMID- 25984796
TI  - A geometrical model for the Monte Carlo simulation of the TrueBeam linac.
AB  - Monte Carlo simulation of linear accelerators (linacs) depends on the accurate
      geometrical description of the linac head. The geometry of the Varian TrueBeam
      linac is not available to researchers. Instead, the company distributes phase
      space files of the flattening-filter-free (FFF) beams tallied at a plane located
      just upstream of the jaws. Yet, Monte Carlo simulations based on third-party
      tallied phase spaces are subject to limitations. In this work, an experimentally
      based geometry developed for the simulation of the FFF beams of the Varian
      TrueBeam linac is presented. The Monte Carlo geometrical model of the TrueBeam
      linac uses information provided by Varian that reveals large similarities between
      the TrueBeam machine and the Clinac 2100 downstream of the jaws. Thus, the upper
      part of the TrueBeam linac was modeled by introducing modifications to the Varian
      Clinac 2100 linac geometry. The most important of these modifications is the
      replacement of the standard flattening filters by ad hoc thin filters. These
      filters were modeled by comparing dose measurements and simulations. The
      experimental dose profiles for the 6 MV and 10 MV FFF beams were obtained from
      the Varian Golden Data Set and from in-house measurements performed with a diode
      detector for radiation fields ranging from 3  *  3 to 40  *  40 cm(2) at depths
      of maximum dose of 5 and 10 cm. Indicators of agreement between the experimental
      data and the simulation results obtained with the proposed geometrical model were
      the dose differences, the root-mean-square error and the gamma index. The same
      comparisons were performed for dose profiles obtained from Monte Carlo
      simulations using the phase-space files distributed by Varian for the TrueBeam
      linac as the sources of particles. Results of comparisons show a good agreement
      of the dose for the ansatz geometry similar to that obtained for the simulations
      with the TrueBeam phase-space files for all fields and depths considered, except
      for the 40  *  40 cm(2) field where the ansatz geometry was able to reproduce the
      measured dose more accurately. Our approach overcomes some of the limitations of
      using the Varian phase-space files. It makes it possible to: (i) adapt the
      initial beam parameters to match measured dose profiles; (ii) reduce the
      statistical uncertainty to arbitrarily low values; and (iii) assess systematic
      uncertainties (type B) by using different Monte Carlo codes. One limitation of
      using phase-space files that is retained in our model is the impossibility of
      performing accurate absolute dosimetry simulations because the geometrical
      description of the TrueBeam ionization chamber remains unknown.

PMID- 25984794
TI  - Moving to Second-Stage Treatments Faster: Identifying Midtreatment Tailoring
      Variables for Youth with Anxiety Disorders.
AB  - The current study presents an approach for empirically identifying tailoring
      variables at midtreatment of cognitive behavioral therapy (CBT) protocols for
      youth with anxiety disorders that can be used to guide moves to second-stage
      treatments. Using 2 independent data sets (Study 1 N = 240, M age = 9.86 years;
      Study 2 N = 341; M age = 9.53 years), we examined treatment response patterns
      after 8 sessions of CBT (i.e., CBT midtreatment). We identified and replicated 3
      classes of response patterns at CBT midtreatment: Early Responders, Partial
      Responders, and Nonresponders. Class membership at CBT midtreatment was
      predictive of outcome at CBT posttreatment. Receiver operating characteristics
      curves were used to derive guidelines to optimize accuracy of assignment to
      classes at CBT midtreatment. These findings support the promise of treatment
      response at CBT midtreatment to identify tailoring variables for use in
      abbreviating first-stage treatments and facilitating moves to second-stage
      treatments.

PMID- 25984798
TI  - Dissemination and Implementation of Manualized Family-Based Treatment: A
      Systematic Review.
AB  - The objective of this article was to systematically review the literature
      pertaining to the dissemination and implementation of manualized family-based
      treatment (FBT). Several studies were found looking at the dissemination of FBT
      to sites beyond those of the primary research, mainly focusing on patient
      outcomes. Alternatively, articles were found which focused primarily on
      implementation outcomes, such as the barriers and facilitating factors for FBT
      uptake, a knowledge transfer model that could be applied to improve uptake, and
      team decision-making processes. It remains important to study the implementation
      of FBT in clinical practice due to the barriers identified in the literature. 

PMID- 25984799
TI  - Selective Access to 3-Cyano-1H-indoles, 9H-Pyrimido[4,5-b]indoles, or 9H
      Pyrido[2,3-b]indoles through Copper-Catalyzed One-Pot Multicomponent Cascade
      Reactions.
AB  - Novel and selective synthetic approaches toward indole derivatives via copper
      catalyzed one-pot multicomponent cascade reactions of 1-bromo-2-(2,2
      dibromovinyl)benzenes with aldehydes and aqueous ammonia are presented.
      Intriguingly, the concentration of ammonia, the molar ratio of reagents, and the
      structural features of the aldehyde substrate serve as key factors in controlling
      the selective formation of 3-cyano-1H-indoles, 9H-pyrimido[4,5-b]indoles, or 9H
      pyrido[2,3-b]indoles. Compared with literature procedures, the synthetic
      approaches reported herein have advantages such as readily available starting
      materials, mild reaction conditions, and divergent reaction patterns toward
      different products with easily tunable selectivity. 

PMID- 25984800
TI  - Muscular Strength and Power in 3-to 7-Year-Old Children.
AB  - To determine absolute and relative (adjusted for body mass) strength, mean power,
      and mean velocity for upper and lower body resistance exercises, forty-seven
      young boys and girls participated in maximal strength testing. Healthy young boys
      and girls, ages 3- to 7-years old, were tested for one-repetition maximum (1-RM)
      strength, and 70% of 1-RM to determine mean power and mean velocity on the chest
      press and leg press exercises. Adult weight machines were modified to accommodate
      the smaller size and lower strength levels of the children. A 2 * 4 (sex * age)
      ANOVA was used to determine age and sex differences in performance. No
      interaction or sex differences were observed for any variable at any age. 1-RM
      strength, mean power, and mean velocity significantly increased across ages (p <=
      .05). When adjusted for body mass, the changes were insignificant, with one
      exception. Relative mean power for the bench press increased with age. Data
      indicated children from 3-7 years of age are capable of performing strength and
      power tests, but may require more attempts at maximal loads compared with adults.
      It appears that muscular strength and velocity during this stage of development
      are primarily dependent on increasing body mass, whereas power is influenced by
      additional variable(s). 

PMID- 25984797
TI  - Biomarkers for circadian rhythm disruption independent of time of day.
AB  - Frequent shift work causes disruption of the circadian rhythm and might on the
      long-term result in increased health risk. Current biomarkers evaluating the
      presence of circadian rhythm disturbance (CRD), including melatonin, cortisol and
      body temperature, require 24-hr ("around the clock") measurements, which is
      tedious. Therefore, these markers are not eligible to be used in large-scale
      (human) studies. The aim of the present study was to identify universal
      biomarkers for CRD independent of time of day using a transcriptomics approach.
      Female FVB mice were exposed to six shifts in a clockwise (CW) and
      counterclockwise (CCW) CRD protocol and sacrificed at baseline and after 1 shift,
      6 shifts, 5 days recovery and 14 days recovery, respectively. At six time-points
      during the day, livers were collected for mRNA microarray analysis. Using a
      classification approach, we identified a set of biomarkers able to classify
      samples into either CRD or non-disrupted based on the hepatic gene expression.
      Furthermore, we identified differentially expressed genes 14 days after the last
      shift compared to baseline for both CRD protocols. Non-circadian genes
      differentially expressed upon both CW and CCW protocol were considered useful,
      universal markers for CRD. One candidate marker i.e. CD36 was evaluated in serum
      samples of the CRD animals versus controls. These biomarkers might be useful to
      measure CRD and can be used later on for monitoring the effectiveness of
      intervention strategies aiming to prevent or minimize chronic adverse health
      effects. 

PMID- 25984801
TI  - Self-Assembly of Nanometer-Sized Boroxine Cages from Diboronic Acids.
AB  - By use of the reversible trimerization of boronic acids, the series of boroxine
      cages 3-mer, 6-mer, and 12-mer were constructed from rationally designed
      diboronic acids whose bond angles between two C-B bonds are 60 degrees , 84
      degrees , and 117 degrees , respectively. Boroxine cages 6-mer and 12-mer have
      1.5 and 2.5 nm sized cavities, respectively. 

PMID- 25984802
TI  - Balancing effectiveness with responsiveness: Therapist satisfaction across
      different treatment designs in the Child STEPs randomized effectiveness trial.
AB  - OBJECTIVE: To investigate the association between protocol design and therapist
      satisfaction in the Child STEPs Randomized Effectiveness Trial (Weisz et al.,
      2012). METHOD: Therapist report was obtained at the close of 145 cases seen by 77
      therapists, each of whom was randomized to a Standard evidence-based treatment
      (EBT), modular EBT, or usual care (UC) condition. RESULTS: Analysis of
      satisfaction items revealed 2 correlated factors representing perceived
      effectiveness and perceived responsiveness of the treatments. Therapist total
      satisfaction scores were significantly higher for cases in the modular condition
      than for those in the standard EBT or UC conditions. With regard to specific
      dimensions, the modular and UC cases were rated significantly higher than
      standard EBT cases on the Responsiveness scale, whereas modular and standard EBT
      cases were rated significantly higher than UC on the Effectiveness scale.
      Finally, increases in Effectiveness scores from first to second case were
      significantly larger for Modular cases than for cases in both other study
      conditions, and increases from first to second case in Total Satisfaction scores
      were significantly larger for modular cases than for UC cases. CONCLUSIONS:
      Therapist satisfaction with a treatment approach has independent dimensions,
      which can vary as a function of the protocol design. By virtue of being perceived
      as more effective than UC and more responsive than standard EBTs, the modular
      protocol design was also viewed as more overall satisfying than both, and
      secondary analysis suggested that these results were not due to mere first
      impressions of the protocols.

PMID- 25984803
TI  - The Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related
      Conditions (MOSAIC): Comparison of the Maudsley Model of Anorexia Nervosa
      Treatment for Adults (MANTRA) with specialist supportive clinical management
      (SSCM) in outpatients with broadly defined anorexia nervosa: A randomized
      controlled trial.
AB  - OBJECTIVE: Anorexia nervosa (AN) in adults has poor outcomes, and treatment
      evidence is limited. This study evaluated the efficacy and acceptability of a
      novel, targeted psychological therapy for AN (Maudsley Model of Anorexia Nervosa
      Treatment for Adults; MANTRA) compared with Specialist Supportive Clinical
      Management (SSCM). METHOD: One hundred forty-two outpatients with broadly defined
      AN (body mass index [BMI] <= 18.5 kg/m2) were randomly allocated to receive 20 to
      30 weekly sessions (depending on clinical severity) plus add-ons (4 follow-up
      sessions, optional sessions with dietician and with carers) of MANTRA (n = 72) or
      SSCM (n = 70). Assessments were administered blind to treatment condition at
      baseline, 6 months, and 12 months after randomization. The primary outcome was
      BMI at 12 months. Secondary outcomes included eating disorders symptomatology,
      other psychopathology, neuro-cognitive and social cognition, and acceptability.
      Additional service utilization was also assessed. Outcomes were analyzed using
      linear mixed models. RESULTS: Both treatments resulted in significant
      improvements in BMI and reductions in eating disorders symptomatology, distress
      levels, and clinical impairment over time, with no statistically significant
      difference between groups at either 6 or 12 months. Improvements in neuro
      cognitive and social-cognitive measures over time were less consistent. One SSCM
      patient died. Compared with SSCM, MANTRA patients rated their treatment as
      significantly more acceptable and credible at 12 months. There was no significant
      difference between groups in additional service consumption. CONCLUSIONS: Both
      treatments appear to have value as first-line outpatient interventions for
      patients with broadly defined AN. Longer term outcomes remain to be evaluated.

PMID- 25984805
TI  - Prospecting in the field of developmental coordination disorder.

PMID- 25984806
TI  - Ten Conferences on Developmental Coordination Disorder (DCD): A Brief Commentary
      on 20 Years of Research.

PMID- 25984807
TI  - European-French Cross-Cultural Adaptation of the Developmental Coordination
      Disorder Questionnaire and Pretest in French-Speaking Switzerland.
AB  - The Developmental Coordination Disorder Questionnaire (DCDQ'07) is a Canadian
      English instrument recommended for screening children aged 5 to 15 years who are
      at risk for developmental coordination disorder. While a Canadian-French version
      of the DCDQ'07 presently exists, a European-French version does not. AIMS: To
      produce a cross-cultural adaptation of the DCDQ'07 for use in areas of Europe
      where French is spoken and to test its cultural relevance in French-speaking
      Switzerland. METHODS: Cross-cultural adaptation was done using established
      guidelines. Cultural relevance was analyzed with cognitive interviews of thirteen
      parents of children aged 5.0 to 14.6 years (mean age: 8.5 years, SD = 3.4), using
      think-aloud and probing techniques. RESULTS: Cultural and linguistic differences
      were noted between the European-French, the Canadian-French, and the original
      versions of the DCDQ'07. Despite correct translation and expert committee review,
      cognitive interviews revealed that certain items of the European-French version
      were unclear or misinterpreted and further modifications were needed.
      CONCLUSIONS: After rewording items as a result of the outcomes of the cognitive
      interview, the European-French version of the DCDQ'07 is culturally appropriate
      for use in French-speaking Switzerland. Further studies are necessary to
      determine its psychometric properties.

PMID- 25984808
TI  - Health Promotion in a Low-income Primary School: Children with and Without DCD
      Benefit, but Differently.
AB  - Poor motor performance and reduced physical fitness are characteristic of
      children with Developmental Coordination Disorder (DCD). These features have also
      been identified more frequently among children living in low socio-economic
      circumstances. AIMS: To evaluate the outcomes of a nine-week health promotion
      program (HPP) on the motor performance and fitness levels of children (6-10
      years) with and without DCD attending a low-income primary school. METHODS: The
      HPP was designed and implemented by undergraduate physiotherapy students using
      guidelines from the World Health Organization School Health Initiative and their
      physiotherapy curriculum. Children with DCD (n = 22) and a control group without
      DCD (n = 19) participated in the evaluation. Motor skill, functional strength,
      aerobic capacity, and anaerobic power were measured at baseline and after nine
      weeks. RESULTS: Both groups of children improved on all measures at the
      conclusion of the HPP. Children with DCD showed greater improvement than the
      control group in motor performance and the control group showed greater
      improvement on one of the anaerobic fitness outcomes. CONCLUSIONS: A school-based
      HPP that focuses on increasing opportunities for physical activity may be
      effective in improving motor performance in children with DCD and can increase
      fitness levels in general.

PMID- 25984809
TI  - Pelvic organ prolapse and stress urinary incontinence, do they share the same
      risk factors?
AB  - OBJECTIVE: To determine whether there are differences in the etiologies of two of
      the most common pelvic floor disorders (PFD), pelvic organ prolapse (POP) and
      stress urinary incontinence (SUI). STUDY DESIGN: This cross-sectional descriptive
      study included 1042 women, referred to a pelvic floor unit in a tertiary Spanish
      hospital, between 2008 and 2012. Subjects at their fist visit were interviewed
      and examined generally and specifically (medical and urogynecological history).
      Collected parameters included: age, weight, height, medical and surgical
      background (including in-depth obstetrical and gynecological characteristics).
      The participants were classified into 3 different groups (POP, SUI, and mixed
      pathology). Descriptive analyses of each variable and multinomial logistic
      regression were performed to determine factors associated with POP and SUI.
      RESULTS: Patients with POP were older, thinner, with greater parity and their
      newborns tended to be heavier. Furthermore, forceps, vaginal tears and vaginal
      surgeries were more common in the POP group. In contrast, family history was an
      important factor for the development of SUI, with a 6.45-fold increase (95% CI:
      3.69-11.24). Two protective factors were identified for POP, cesarean section
      reduces the risk by 3 fold (OR=0.33) (95% CI: 0.13-0.85) whereas pelvic floor
      rehabilitation produces a 2 fold reduction (OR=0.49) (95% CI: 0.31-0.76).
      CONCLUSIONS: Our data study demonstrates differences in potential triggers and
      risk factors for POP and SUI. Cesarean section and pelvic floor rehabilitation
      have a protective effect on preventing the development of POP. Bringing up that a
      personal medical care and a specific urogynecological follow-up should be
      developed for those who are more susceptible or at risk of PFD.

PMID- 25984810
TI  - Biotemplate-directed fabrication of size-controlled monodisperse magnetic silica
      microspheres.
AB  - Biotemplating is an effective strategy to obtain morphology-controllable
      materials with structural specificity, complexity, and corresponding unique
      functions. Herein we take advantage of the unique heavy-metal-ion biosorption
      behavior of cyanobacteria cells to fabricate Fe3O4/cell composites. Meanwhile,
      cyanobacteria cells served as a biotemplate for fabricating solid and hollow
      magnetic silica microspheres (MSMs). The obtained MSMs retained the original
      morphology of the cells, and exhibited excellent monodispersity and uniform
      spherical shape with narrow size distribution. Furthermore, they demonstrated
      ferromagnetic behavior at room temperature when measured using a vibrating sample
      magnetometer. 

PMID- 25984811
TI  - Developmental Trajectories of Physical Activity, Sports, and Television Viewing
      During Childhood to Young Adulthood: Iowa Bone Development Study.
AB  - IMPORTANCE: The diverse developmental patterns of obesogenic behaviors during
      childhood and adolescence can be better understood by using new analytic
      approaches to assess the heterogeneity in variation during growth and development
      and to map the clustering of behavior patterns. OBJECTIVES: To identify distinct
      trajectories of daily time spent in moderate- to vigorous-intensity physical
      activity (MVPA) from ages 5 to 19 years and to examine the associations of MVPA
      trajectories with sports participation and television viewing trajectories.
      DESIGN, SETTING, AND PARTICIPANTS: Cohort members in the prospective population
      based Iowa Bone Development Study participated in MVPA assessments via
      accelerometry from September 16, 1998, to December 9, 2013, at ages 5, 8, 11, 13,
      15, 17, and 19 years and completed a questionnaire every 6 months on sports
      participation and daily time spent in television viewing. MAIN OUTCOMES AND
      MEASURES: Trajectories of MVPA (minutes per day), participation in organized
      sports (yes or no), and television viewing time (hours per day). RESULTS: Based
      on the data from 537 participants (50.1% females; 94.6% white), we identified 4
      MVPA trajectories: consistently inactive (14.9%), consistently active (18.1%),
      decreasing moderate physical activity (52.9%), and substantially decreasing high
      physical activity (14.1%). All participants in the consistently inactive
      trajectory also followed a trajectory of no participation in sports. The
      consistently active trajectory was associated with decreasing an already low
      television viewing trajectory (P < .001). CONCLUSIONS AND RELEVANCE: This study
      provided a nuanced look at the known decrease in MVPA during childhood and
      adolescence. Sports participation could be a critical way to avoid the
      consistently inactive pattern. Most important, we identified a subset of
      participants who maintained a seemingly healthy level of MVPA from childhood to
      young adulthood. The developmental pathways of physical activity and television
      viewing behaviors could be related. Additional studies should examine the
      determinants and health consequences of these specific MVPA trajectories.

PMID- 25984812
TI  - Osteoarthritis increases the risk of dementia: a nationwide cohort study in
      Taiwan.
AB  - Osteoarthritis (OA) and dementia are prevalent causes of disability in geriatric
      patients. To date, information on the temporal correlation between these
      progressive diseases and the risk of dementia in patients with OA is limited.
      This retrospective population-based 4-year cohort study investigated the risk of
      dementia in patients with OA. We performed a case-control matched analysis by
      using the Taiwan Longitudinal Health Insurance Database 2005. Patients were
      selected on the basis of International Classification of Diseases, Ninth
      Revision, Clinical Modification codes for OA between January 1, 2004 and December
      31, 2007. The prevalence and the adjusted hazard ratio (HR) of dementia in
      patients with and without OA were estimated. The OA cohort comprised 35,149
      patients and the non-OA cohort (comparison cohort) comprised 70,298 patients
      (1:2). The incidence of dementia was 21.7 per 10,000 person-years in the OA
      cohort and 14.7 per 10,000 person-years in the non-OA cohort. The HR for dementia
      during the follow-up period was 1.33 (95% confidence interval [CI], 1.17-1.50, P
      < 0.001) for patients with OA. The adjusted HR for dementia was 1.25 (95% CI,
      1.10-1.43, P < 0.001) for patients with OA. The results of this study indicated
      that OA is an independent risk factor for dementia.

PMID- 25984813
TI  - Large-scale parallel alignment of platelet-shaped particles through gravitational
      sedimentation.
AB  - Parallel and concentric alignment of microscopic building blocks into several
      orders of magnitude larger structures is commonly observed in nature. However, if
      similarly aligned structures are artificially produced their thickness is
      generally limited to just about one or two orders of magnitude more than the
      dimensions of the smallest element. We show that sedimentation provides a
      promising approach to manufacture solid materials consisting of well-aligned
      platelet-shaped particles while being more than 30,000 times thicker than the
      individual particle. Such sediments contain up to 28 vol% of particles without
      any further treatment and can be densified to 67 vol% particle fraction by
      subsequent unidirectional pressing. The degree of orientation of the platelet
      shaped particles within the sediments was tracked by high-energy X-ray
      diffraction measurements. The Hermans orientation parameter, a statistical
      measure of the quality of alignment, was determined to be 0.63 +/- 0.03 already
      for as-sedimented samples while the standard deviation of the orientation
      distribution of particles, another measure of average misalignment, was found to
      be (21.5 +/- 1.4) degrees . After pressing, these values further improved to
      (0.81 +/- 0.01) and (14.6 +/- 0.4) degrees , respectively. Such quality of
      alignment competes with, if not even exceeds, values reported in the literature.

PMID- 25984814
TI  - Supramolecular assembly of isocyanorhodium(I) complexes: an interplay of
      rhodium(I)...rhodium(I) interactions, hydrophobic-hydrophobic interactions, and
      host-guest chemistry.
AB  - A series of tetrakis(isocyano)rhodium(I) complexes with different chain lengths
      of alkyl substituents has been found to exhibit a strong tendency toward solution
      state aggregation upon altering the concentration, temperature and solvent
      composition. Temperature- and solvent-dependent UV-vis absorption studies have
      been performed, and the data have been analyzed using the aggregation model to
      elucidate the growth mechanism. The aggregation is found to involve extensive
      Rh(I)...Rh(I) interactions that are synergistically assisted by hydrophobic
      hydrophobic interactions to give a rainbow array of solution aggregate colors. It
      is noted that the presence of three long alkyl substituents is crucial for the
      observed cooperativity in the aggregation. Molecular assemblies in the form of
      nanoplates and nanovesicles have been observed in the hexane-dichloromethane
      solvent mixtures, arising from the different formation mechanisms based on the
      alkyl chain length of the complexes. Benzo-15-crown-5 moieties have been
      incorporated for selective potassium ion binding to induce dimer formation and
      drastic color changes, rendering the system as potential colorimetric and
      luminescent cation sensors and as building blocks for ion-controlled
      supramolecular assembly. 

PMID- 25984815
TI  - Uptake, Translocation, and Metabolism of Phenols by Submerged Rooted Macrophyte,
      Water Milfoil (Myriophyllum elatinoides).
AB  - Shoot and root uptakes of (14)C-labeled phenol (1), 4-nitrophenol (2), 4
      cyanophenol (3), 4-hydroxybenzamide (4), and 4-hydroxybenzoic acid (5) by
      Myriophyllum elatinoides were individually examined with water or sediment
      treatments using the sequestered chamber. Shoot uptake of each (14)C-phenol
      dissolved in water amounted to 21.0% (1), 14.3% (2), 12.8% (3), 4.2% (4) and
      41.7% (5) of the applied radioactivity (AR) after 96 h without significant (14)C
      translocation from shoot to root (<=0.9% AR), and the major metabolite produced
      was the glucose conjugate. On the other hand, root uptake of (14)C-phenols from
      sediment was much slower/smaller (<=6.6% AR), and (14)C transportation from root
      to shoot was scarcely observed, except for compound 5 (<=1.5% AR). For the water
      treatment, a kinetic analysis on uptake/metabolism was conducted using the
      assumed compartment. Good correlation was observed between lipophilicity and
      shoot uptake rate constants, and the electronic state of the hydroxyl group
      (sigma, sigma(-), or EHOMO(OH)) and the transformation rate constant of
      glucosidation. 

PMID- 25984816
TI  - Visible Light-Driven Artificial Molecular Switch Actuated by Radical-Radical and
      Donor-Acceptor Interactions.
AB  - We describe a visible light-driven switchable [2]catenane, composed of a
      Ru(bpy)3(2+) tethered cyclobis(paraquat-p-phenylene) (CBPQT(4+)) ring that is
      interlocked mechanically with a macrocyclic polyether consisting of electron-rich
      1,5-dioxynaphthalene (DNP) and electron-deficient 4,4'-bipyridinium (BIPY(2+))
      units. In the oxidized state, the CBPQT(4+) ring encircles the DNP recognition
      site as a consequence of favorable donor-acceptor interactions. In the presence
      of an excess of triethanolamine (TEOA), visible light irradiation reduces the
      BIPY(2+) units to BIPY((*+)) radical cations under the influence of the
      photosensitizer Ru(bpy)3(2+), resulting in the movement of the CBPQT(2(*+)) ring
      from the DNP to the BIPY((*+)) recognition site as a consequence of the formation
      of the more energetically favorable trisradical complex, BIPY((*+)) ?
      CBPQT(2(*+)). Upon introducing O2 in the dark, the BIPY((*+)) radical cations are
      oxidized back to BIPY(2+) dications, leading to the reinstatement of the
      CBPQT(4+) ring encircled around the DNP recognition site. Employing this strategy
      of redox control, we have demonstrated a prototypical molecular switch that can
      be manipulated photochemically and chemically by sequential reduction and
      oxidation. 

PMID- 25984817
TI  - The investigation of prostatic calcifications using MU-PIXE analysis and their
      dosimetric effect in low dose rate brachytherapy treatments using Geant4.
AB  - Low dose rate brachytherapy is a widely used modality for the treatment of
      prostate cancer. Most clinical treatment planning systems currently in use
      approximate all tissue to water, neglecting the existence of inhomogeneities,
      such as calcifications. The presence of prostatic calcifications may perturb the
      dose due to the higher photoelectric effect cross section in comparison to water.
      This study quantitatively evaluates the effect of prostatic calcifications on the
      dosimetric outcome of brachytherapy treatments by means of Monte Carlo
      simulations and its potential clinical consequences.Four pathological
      calcification samples were characterised with micro-particle induced x-ray
      emission (MU-PIXE) to determine their heavy elemental composition. Calcium,
      phosphorus and zinc were found to be the predominant heavy elements in the
      calcification composition. Four clinical patient brachytherapy treatments were
      modelled using Geant4 based Monte Carlo simulations, in terms of the distribution
      of brachytherapy seeds and calcifications in the prostate. Dose reductions were
      observed to be up to 30% locally to the calcification boundary, calcification
      size dependent. Single large calcifications and closely placed calculi caused
      local dose reductions of between 30-60%. Individual calculi smaller than 0.5 mm
      in diameter showed minimal dosimetric impact, however, the effects of small or
      diffuse calcifications within the prostatic tissue could not be determined using
      the methods employed in the study. The simulation study showed a varying
      reduction on common dosimetric parameters. D90 showed a reduction of 2-5%,
      regardless of calcification surface area and volume. The parameters V100, V150
      and V200 were also reduced by as much as 3% and on average by 1%. These
      reductions were also found to relate to the surface area and volume of
      calcifications, which may have a significant dosimetric impact on brachytherapy
      treatment, however, such impacts depend strongly on specific factors in the
      patient's individual treatment. These factors include the number, size,
      composition and spatial distribution of calcifications in the prostate as well as
      the distribution of brachytherapy seeds.

PMID- 25984818
TI  - A composite measure of gender and its association with risk factors in patients
      with premature acute coronary syndrome.
AB  - OBJECTIVE: To create a gender index by using principal component analyses (PCA)
      and logistic regression, and to determine the association between gender, sex,
      and cardiovascular risk factors among patients with premature acute coronary
      syndrome (ACS). METHODS: GENESIS-PRAXY is a cohort study including ACS patients
      aged 55 years or below, and with ACS recruited between 2009 and 2013 from 26
      centres across Canada, the United States, and Switzerland. A sample of 1075
      patients was used for this study. Psychosocial variables assumed to differ
      between sexes (i.e., gender related) were included in PCA. Variables identified
      on retained components were included in logistic regressions where coefficient
      estimates of variables associated with sex were used to calculate a gender score.
      Cardiovascular risk factors were assessed using self-report and chart review
      data. RESULTS: After the inclusion of 26 psychosocial variables in PCA, we
      identified 17 variables within retained components; 7 of which were associated
      with sex in logistic regression. The gender distribution revealed that half of
      women had a more androgyne or masculine gender score, and 16% of men exhibited a
      more feminine gender score. In univariable analyses, feminine gender scores and
      female sex were associated with hypertension, diabetes, family history of
      cardiovascular disease (only gender), and depressive/anxious symptoms. In
      multivariable models including both gender score and sex, feminine gender score
      but not female sex was associated with the presence of risk factors. CONCLUSIONS:
      Sex and gender are distinct constructs, and the derived gender index offers a
      current and pragmatic option to measure gender within ACS populations. Our
      results further suggest that traditional sex differences in cardiovascular
      disease risk factors may be partly explained by patient's gender-related
      characteristics.

PMID- 25984819
TI  - Altered patterns of heartbeat-evoked potentials in
      depersonalization/derealization disorder: neurophysiological evidence for
      impaired cortical representation of bodily signals.
AB  - OBJECTIVE: Core features of depersonalization/derealization disorder (DPD) are
      emotional numbing and feelings of disembodiment. Although there are several
      neurophysiological findings supporting subjective emotional numbing, the
      psychobiology of disembodiment remains unclear. METHODS: Heartbeat-evoked
      potentials (HEPs), which are considered psychophysiological indicators for the
      cortical representation of afferent signals originating from the cardiovascular
      system, were assessed in 23 patients with DPD and 24 healthy control individuals
      during rest and while performing a heartbeat perception task. RESULTS: Absolute
      HEP amplitudes did not differ between groups. Nevertheless, healthy individuals
      showed higher HEPs during the heartbeat perception task than during rest, whereas
      no such effect was found in patients with DPD (p = .031). Patients with DPD had
      higher total levels of salivary alpha-amylase than did healthy individuals
      (9626.6 [8200.0] versus 5344.3 [3745.8] kU min/l; p = .029), but there were no
      group differences in cardiovascular measures (heart rate = 76.2 [10.1] versus
      74.3 [7.5] beats/min, p = .60; normalized low-frequency heart rate variability =
      0.63 [0.15] versus 0.56 [0.15] normalized units, p = .099; low frequency/high
      frequency ratio = 249.3 [242.7] versus 164.8 [108.8], p = .10), salivary cortisol
      (57.5 [46.7] versus 55.1 [43.6] nmol min/l, p = .86), or cortisone levels (593.2
      [260.3] versus 543.8 [257.1] nmol min/l, p = .52). CONCLUSIONS: These results
      suggest altered cortical representation of afferent signals originating from the
      cardiovascular system in patients with DPD, which may be associated with higher
      sympathetic tone. These findings may reflect difficulties of patients with DPD to
      attend to their actual bodily experiences.

PMID- 25984820
TI  - Prediction of daily food intake as a function of measurement modality and
      restriction status.
AB  - OBJECTIVE: Research on eating relies on various indices (e.g., stable, momentary,
      neural) to accurately reflect food-related reactivity (e.g., disinhibition) and
      regulation (e.g., restraint) outside the laboratory. The degree to which they
      differentially predict real-world consumption remains unclear. Further, the
      predictive validity of these indices might vary depending on whether an
      individual is actively restricting intake. METHODS: We assessed food craving
      reactivity and regulation in 46 healthy participants (30 women, 18-30 years)
      using standard measurements in three modalities: a) self-reported (stable) traits
      using surveys popular in the eating literature, and b) momentary craving ratings
      and c) neural activation using aggregated functional magnetic resonance imaging
      data gathered during a food reactivity-and-regulation task. We then used these
      data to predict variance in real-world consumption of craved energy-dense
      "target" foods across 2 weeks among normal-weight participants randomly assigned
      to restrict or monitor target food intake. RESULTS: The predictive validity of
      four indices varied significantly by restriction. When participants were not
      restricting intake, momentary (B = 0.21, standard error [SE] = 0.05) and neural
      (B = 0.08, SE = 0.04) reactivity positively predicted consumption, and stable (B
      = -0.22, SE = 0.05) and momentary (B = -0.24, SE = 0.05) regulation negatively
      predicted consumption. When restricting, stable (B = 0.36, SE = 0.12) and neural
      (B = 0.51, SE = 0.12) regulation positively predicted consumption. CONCLUSIONS:
      Commonly-used indices of regulation and reactivity differentially relate to an
      ecologically-valid eating measurement, depending on the presence of restriction
      goals, and thus have strong implications for predicting real-world behaviors.

PMID- 25984821
TI  - Depression and risk of venous thromboembolism: a population-based retrospective
      cohort study.
AB  - OBJECTIVE: This study investigated the relationship between depression and the
      risk of subsequent venous thromboembolism (VTE) development. METHODS: We
      conducted a population-based retrospective cohort analysis by using data for the
      period of 2000 to 2011 from the Longitudinal Health Insurance Database 2000 of
      Taiwan. A depression cohort comprising 35,274 patients and a nondepression cohort
      comprising 70,548 patients matched according to sex, age, and index year with no
      history of VTE were evaluated. Cox proportional hazard regression analysis was
      used to assess the effects of depression and comorbidities, and the Kaplan-Meier
      method was applied to estimate the cumulative VTE incidence curves. RESULTS:
      Compared with individuals without depression, depressed patients had a 1.38-fold
      greater risk (95% confidence interval = 1.09-1.73) of developing VTE. This risk
      was significantly higher in male and younger (<=49 years) patients. In addition,
      patients with comorbidities such as hypertension, diabetes, heart failure, and
      cancer had a higher risk of depression-associated VTE that was attenuated,
      although nonsignificantly, by antidepressant use. CONCLUSIONS: The incidence of
      VTE in Taiwan is higher in depressed patients than in nondepressed patients.
      Moreover, men, people 49 years or younger, and patients with comorbidities have a
      significantly greater risk of VTE after depression.

PMID- 25984822
TI  - Unexplained acute chest pain in young adults: disease patterns and medication use
      25 years later.
AB  - BACKGROUND: Patients with unexplained chest pain are commonly revisiting an
      emergency department with various symptoms, but comprehensive long-term studies
      are lacking. METHODS: A total of 150 young adults (aged 18-40 years) with
      unexplained chest pain who presented at an emergency unit for 16 weeks in mid
      1980s were included in a prospective cohort study. An age- and sex-matched
      control group was randomly selected from the same area. Data were retrieved from
      registers that recorded death, income, education, country of birth, diagnoses,
      hospitalizations, outpatient visits, and medications dispensed. RESULTS: Patients
      with unexplained acute chest pain had lower levels of education and income and
      were more often immigrants. Long-term mortality rates did not differ between
      cases (4%) and controls (5%) during 25 years of follow-up, nor were there
      differences in diagnosis of ischemic heart disease. Patients with unexplained
      acute chest pain had more outpatient visits (median, 5 versus 2; p < .0001) and
      had more often been hospitalized (61.6% ever versus 41.8%; p < .001) during the
      follow-up period. Several disorders were more common among patients 20 to 25
      years later, including atrial fibrillation, esophageal/gastric disorders, chest
      pain, palpitations, abdominal discomfort, musculoskeletal symptoms, sleeping
      disturbance, and stress reactions (p values < .05). More patients had been given
      antihypertensives, anticoagulants, antidepressants, analgesics, and
      hypnotics/tranquilizers (p values < .05). CONCLUSIONS: Young patients admitted to
      the emergency department with unexplained acute chest pain showed no increased
      risk of mortality or ischemic heart disease during 25 years of follow-up, but
      they had higher incidence of a wide range of disorders and used more medications.
      Early identification and preventive interventions may improve health outcomes in
      these patients.

PMID- 25984823
TI  - Reaction time in adolescence, cumulative allostatic load, and symptoms of anxiety
      and depression in adulthood: the West of Scotland Twenty-07 Study.
AB  - OBJECTIVE: To examine the relation between reaction time in adolescence and
      subsequent symptoms of anxiety and depression and investigate the mediating role
      of sociodemographic measures, health behaviors, and allostatic load. METHODS:
      Participants were 705 members of the West of Scotland Twenty-07 Study. Choice
      reaction time was measured at age 16. At age 36 years, anxiety and depression
      were assessed with the 12-item General Health Questionnaire (GHQ) and the
      Hospital Anxiety and Depression Scale (HADS), and measurements were made of blood
      pressure, pulse rate, waist-to-hip ratio, and total and high-density lipoprotein
      cholesterol, C-reactive protein, albumin, and glycosolated hemoglobin from which
      allostatic load was calculated. RESULTS: In unadjusted models, longer choice
      reaction time at age 16 years was positively associated with symptoms of anxiety
      and depression at age 36 years: for a standard deviation increment in choice
      reaction time, regression coefficients (95% confidence intervals) for logged GHQ
      score, and square-root-transformed HADS anxiety and depression scores were 0.048
      (0.016-0.080), 0.064 (0.009-0.118), and 0.097 (0.032-0.163) respectively.
      Adjustment for sex, parental social class, GHQ score at age 16 years, health
      behaviors at age 36 years and allostatic load had little attenuating effect on
      the association between reaction time and GHQ score, but weakened those between
      reaction time and the HADS subscales. Part of the effect of reaction time on
      depression was mediated through allostatic load; this mediating role was of
      borderline significance after adjustment. CONCLUSIONS: Adolescents with slower
      processing speed may be at increased risk for anxiety and depression. Cumulative
      allostatic load may partially mediate the relation between processing speed and
      depression.

PMID- 25984824
TI  - Cardiovascular and cortisol reactions to acute psychological stress under
      conditions of high versus low social evaluative threat: associations with the
      type D personality construct.
AB  - OBJECTIVES: Social evaluative threat is an important factor in the cardiovascular
      response to mental stress. This study examined whether Type D personality,
      characterized by social inhibition and negative affectivity, is associated with
      an adverse cardiovascular response to a non-social and social evaluative threat.
      METHODS: A total of 2300 students were screened for Type D personality, and 130
      were selected for a nonsocial stress exposure condition (31 Type D, 30 non-Type
      D: 52% female) or a condition high in social evaluative threat (35 Type D, 34 non
      Type D: 55% female). Systolic (SBP) and diastolic blood pressure (DBP), heart
      rate (HR), and salivary cortisol were measured. RESULTS: Social evaluative threat
      resulted in higher cardiovascular responses than the nonsocial challenge (SBP, p
      = .001, eta = 0.092;DBP, p = .006, eta = 0.058;HR, p = .006, eta = 0.059). The
      greatest cardiovascular stress reactions were exhibited by Type D participants in
      the high social evaluation condition; reflected in significant group by condition
      interactions for SBP (F(1,126) = 7.29, p = .008, eta = 0.055), DBP (F(1,126) =
      5.23, p = .024, eta = 0.040), and HR (F(1,126) = 5.04, p = .027, eta = 0.038)
      reactivity. Only Type Ds in the social condition mounted a positive cortisol
      response (F(1,33) = 5.07, p = .031, eta = 0.133). CONCLUSIONS: Type D individuals
      show different stress reactions depending on the social evaluative nature of the
      stress exposure. These findings suggest that dysregulation of the stress response
      in social situations potentially increases cardiovascular disease risk.

PMID- 25984825
TI  - Injustice at work and leukocyte glucocorticoid sensitivity: findings from a cross
      sectional study.
AB  - OBJECTIVE: Organizational justice refers to perceived fairness at the workplace.
      Low organizational justice has been identified as a major source of distress and
      a predictor of poor health. Impaired regulation of immunological and inflammatory
      pathways may, in part, underlie these health effects. The present study
      investigated the association of organizational justice with leukocyte
      glucocorticoid sensitivity in vivo. METHODS: Organizational justice was assessed
      among 541 male factory workers (mean [standard deviation] age = 46 [9] years) by
      questionnaire. Cortisol release was measured at three time points before blood
      collection and summed as the area under the curve. Blood was used to assess
      leukocyte (white blood cell [WBC] count) subsets (neutrophils [%WBC], lymphocytes
      [%WBC], and the neutrophil/lymphocyte ratio). Glucocorticoid sensitivity was
      operationalized as the correlation between cortisol release and these hematologic
      parameters. Associations were adjusted for demographics, work characteristics,
      and life-style variables. RESULTS: A dose-response relationship between
      organizational justice and glucocorticoid sensitivity was found. Cortisol and
      hematologic parameters showed the expected significant association among
      individuals reporting high (all beta values >= |.26|; all p values <=.001) or
      medium organizational justice (all beta values >= |.15|; all p values <=.050),
      but not among those reporting low organizational justice (all beta values <=
      |.04|; all p values > .10). These regression slopes differed significantly
      between organizational justice groups (p values for interaction < .050).
      CONCLUSIONS: Low justice at work is associated with an impaired ability of
      endogenous cortisol to regulate leukocyte distribution in vivo. These findings
      identify a novel biological pathway by which organizational justice may affect
      health.

PMID- 25984826
TI  - Work stress, caregiving, and allostatic load: prospective results from the
      Whitehall II cohort study.
AB  - OBJECTIVES: Studies investigating health effects of work and family stress
      usually consider these factors in isolation. The present study investigated
      prospective interactive effects of job strain and informal caregiving on
      allostatic load (AL), a multisystem indicator of physiological dysregulation.
      METHODS: Participants were 7007 British civil servants from the Whitehall II
      cohort study. Phase 3 (1991-1994) served as the baseline, and Phases 5 (1997
      1999) and 7 (2002-2004) served as follow-ups. Job strain (high job demands
      combined with low control) and caregiving (providing care to aged or disabled
      relatives) were assessed at baseline. AL index (possible range, 0-9) was assessed
      at baseline and both follow-ups based on nine cardiovascular, metabolic, and
      immune biomarkers. Linear mixed-effect models were used to examine the
      association of job strain and caregiving with AL. RESULTS: High caregiving burden
      (above the sample median weekly hours of providing care) predicted higher AL
      levels, with the effect strongest in those also reporting job strain (b = 0.36,
      95% confidence interval = 0.01-0.71); however, the interaction between job strain
      and caregiving was not significant (p = .56). Regardless of job strain,
      participants with low caregiving burden (below sample median) had lower
      subsequent AL levels than did non-caregivers (b = -0.22, 95% confidence interval
      = -0.06--0.37). CONCLUSIONS: The study provides some evidence for adverse effects
      of stress at work combined with family demands on physiological functioning.
      However, providing care to others may also have health protective effects if it
      does not involve excessive time commitment.

PMID- 25984828
TI  - Low-Energy Bead-Mill Dispersion of Agglomerated Core-Shell alpha-Fe/Al2O3 and
      alpha"-Fe16N2/Al2O3 Ferromagnetic Nanoparticles in Toluene.
AB  - Magnetic materials such as alpha"-Fe16N2 and alpha-Fe, which have the largest
      magnetic moment as hard and soft magnetic materials, are difficult to produce as
      single domain magnetic nanoparticles (MNPs) because of quasistable state and high
      reactivity, respectively. The present work reports dispersion of agglomerated
      plasma-synthesized core-shell alpha"-Fe16N2/Al2O3 and alpha-Fe/Al2O3 in toluene
      by a new bead-mill with very fine beads to prepare single domain MNPs. As a
      result, optimization of the experimental conditions (bead size, rotation speed,
      and dispersion time) enables the break-up of agglomerated particles into primary
      particles without destroying the particle structure. Slight deviation from the
      optimum conditions, i.e., lower or higher dispersion energy, gives undispersed or
      broken particles due to fragile core-shell structure against stress or impact
      force of beads. The dispersibility of alpha"-Fe16N2/Al2O3 is more restricted than
      that of alpha-Fe/Al2O3, because of the preparation conditions. Especially for
      alpha"-Fe16N2/Al2O3, no change on crystallinity (98% alpha"-Fe16N2) or
      magnetization saturation after dispersion was observed, showing that this method
      is appropriate to disperse alpha"-Fe16N2/Al2O3 MNPs. A different magnetic
      hysteresis behavior is observed for well-dispersed alpha"-Fe16N2/Al2O3 MNPs, and
      the magnetic coercivity of these NPs is constricted when the magnetic field close
      to zero due to magnetic dipole coupling among dispersed alpha"-Fe16N2 MNPs. 

PMID- 25984827
TI  - Psychological well-being and metabolic syndrome: findings from the midlife in the
      United States national sample.
AB  - OBJECTIVES: Psychological well-being predicts favorable cardiovascular outcomes,
      but less evidence addresses biological mediators underlying these effects.
      Therefore, associations among well-being and metabolic syndrome (MetSyn) were
      examined in a national sample. METHODS: Survey of Midlife in the US participants
      (MIDUS; n = 1205) provided survey assessments of hedonic (positive affect, life
      satisfaction) and eudaimonic well-being (e.g., personal growth and purpose in
      life) at two waves 9 to 10 years apart. MetSyn components were measured during an
      overnight clinic visit at Time 2 only. Outcomes included the number of MetSyn
      risk factors and a binary outcome reflective of MetSyn status. RESULTS: The
      unadjusted prevalence of MetSyn was 36.6%. Life satisfaction (B [standard error
      {SE}] = -0.12 [0.04], p = .005), positive affect (B [SE] = -0.10 [0.04], p =
      .009), and personal growth (B [SE] = -0.10 [0.04], p = .012) predicted fewer
      MetSyn components and lower risk of meeting diagnostic criteria in fully adjusted
      models. Results were unchanged by adjustments for depressive symptoms, and were
      not moderated by age, sex, race, or socioeconomic status. Life satisfaction (B
      [SE] = -0.11 [0.05], p = .023) and a eudaimonic well-being composite (B [SE] = 
      0.11 [0.05], p = .045) also predicted fewer components and lower risk of meeting
      diagnostic criteria in longitudinal models. CONCLUSIONS: Psychosocial resources,
      including positive affect, life satisfaction, and personal growth, predicted
      reduced risk for MetSyn both cross sectionally and longitudinally. Further work
      should examine consequences of these linkages for cardiovascular outcomes in
      intervention contexts.

PMID- 25984829
TI  - Strain in a silicon-on-insulator nanostructure revealed by 3D x-ray Bragg
      ptychography.
AB  - Progresses in the design of well-defined electronic band structure and dedicated
      functionalities rely on the high control of complex architectural device nano
      scaled structures. This includes the challenging accurate description of strain
      fields in crystalline structures, which requires non invasive and three
      dimensional (3D) imaging methods. Here, we demonstrate in details how x-ray Bragg
      ptychography can be used to quantify in 3D a displacement field in a
      lithographically patterned silicon-on-insulator structure. The image of the
      crystalline properties, which results from the phase retrieval of a coherent
      intensity data set, is obtained from a well-controlled optimized process, for
      which all steps are detailed. These results confirm the promising perspectives of
      3D Bragg ptychography for the investigation of complex nano-structured crystals
      in material science. 

PMID- 25984830
TI  - Effective Oocyte Vitrification and Survival Techniques for Bovine Somatic Cell
      Nuclear Transfer.
AB  - Bovine somatic cell nuclear transfer (SCNT) using vitrified-thawed (VT) oocytes
      has been studied; however, the cloning efficiency of these oocytes is not
      comparable with that of nonvitrified (non-V) fresh oocytes. This study sought to
      optimize the survival and cryopreservation of VT oocytes for SCNT. Co-culture
      with feeder cells that had been preincubated for 15 h significantly improved the
      survival of VT oocytes and their in vitro developmental potential following SCNT
      in comparison to co-culture with feeder cells that had been preincubated for 2,
      5, or 24 h (p<0.05). Spindle assessment via the Oosight Microscopy Imaging System
      and microtubule staining revealed that vitrified metaphase II oocytes (VT group)
      were not suitable for SCNT. However, enucleating and/or activating oocytes prior
      to freezing enhanced their developmental potential and suitability for SCNT. The
      cloning efficiency of the enucleated-activated-vitrified-thawed (EAVT) group
      (21.6%) was better than that of the other vitrification groups [enucleated
      vitrified-thawed (EVT) group, 13.7%; VT group, 15.0%; p<0.05] and was comparable
      with that of the non-V group (25.9%). The reactive oxygen species level was
      significantly lower in the EAVT group than in the other vitrification groups
      (p<0.05). mRNA levels of maternal genes (ZAR1, BMP15, and NLRP5) and a stress
      gene (HSF1) were lower in the vitrification groups than in the non-V group
      (p<0.05), whereas the level of phospho-p44/42 mitogen-activated protein kinase
      did not differ among the groups. Among the vitrification groups, blastocysts in
      the EAVT group had the best developmental potential, as judged by their high mRNA
      expression of developmental potential-related genes (POU5f1, Interferon-tau, and
      SLC2A5) and their low expression of proapoptotic (CASP3) and stress (Hsp70)
      genes. This study demonstrates that SCNT using bovine frozen-thawed oocytes can
      be successfully achieved using optimized vitrification and co-culture techniques.

PMID- 25984831
TI  - Subcellular Raman Microspectroscopy Imaging of Nucleic Acids and Tryptophan for
      Distinction of Normal Human Skin Cells and Tumorigenic Keratinocytes.
AB  - At present, tumor diagnostic imaging is commonly based on hematoxylin and eosin
      or immunohistochemical staining of biopsies, which requires tissue excision,
      fixation, and staining with exogenous marker molecules. Here, we report on label
      free tumor imaging using confocal spontaneous Raman scattering microspectroscopy,
      which exploits the intrinsic vibrational contrast of endogenous biomolecular
      species. We present a chemically specific and quantitative approach to monitoring
      normal human skin cells (keratinocytes and fibroblasts) as well as the human
      HaCaT in vitro skin carcinogenesis model and the tumor-derived MET in vivo skin
      cancer progression model. Mapping the amplitudes of two spectrally well isolated
      Raman bands at 752 and 785 cm(-1) allowed for direct visualization of the
      distributions representative of tryptophan-rich proteins and nucleic acids,
      respectively, with subcellular spatial resolution. Using these Raman markers, it
      was feasible to discriminate between normal human epidermal keratinocytes (NHEK)
      and dermal fibroblasts (NHDF) and to confine all tumorigenic cells from both the
      NHEK and NHDF. First evidence for the successful application of the proposed
      intracellular nucleic acid and tryptophan Raman signatures for skin cancer
      diagnosis was further demonstrated in an organotypic cutaneous squamous cell
      carcinomas model, allowing for the identification of tumor cells and their
      surrounding stroma in the tissue context. 

PMID- 25984832
TI  - Black silicon solar cells with interdigitated back-contacts achieve 22.1%
      efficiency.
AB  - The nanostructuring of silicon surfaces--known as black silicon--is a promising
      approach to eliminate front-surface reflection in photovoltaic devices without
      the need for a conventional antireflection coating. This might lead to both an
      increase in efficiency and a reduction in the manufacturing costs of solar cells.
      However, all previous attempts to integrate black silicon into solar cells have
      resulted in cell efficiencies well below 20% due to the increased charge carrier
      recombination at the nanostructured surface. Here, we show that a conformal
      alumina film can solve the issue of surface recombination in black silicon solar
      cells by providing excellent chemical and electrical passivation. We demonstrate
      that efficiencies above 22% can be reached, even in thick interdigitated back
      contacted cells, where carrier transport is very sensitive to front surface
      passivation. This means that the surface recombination issue has truly been
      solved and black silicon solar cells have real potential for industrial
      production. Furthermore, we show that the use of black silicon can result in a 3%
      increase in daily energy production when compared with a reference cell with the
      same efficiency, due to its better angular acceptance.

PMID- 25984834
TI  - An artificial molecular pump.
AB  - Carrier proteins consume fuel in order to pump ions or molecules across cell
      membranes, creating concentration gradients. Their control over diffusion
      pathways, effected entirely through noncovalent bonding interactions, has
      inspired chemists to devise artificial systems that mimic their function. Here,
      we report a wholly artificial compound that acts on small molecules to create a
      gradient in their local concentration. It does so by using redox energy and
      precisely organized noncovalent bonding interactions to pump positively charged
      rings from solution and ensnare them around an oligomethylene chain, as part of a
      kinetically trapped entanglement. A redox-active viologen unit at the heart of a
      dumbbell-shaped molecular pump plays a dual role, first attracting and then
      repelling the rings during redox cycling, thereby enacting a flashing energy
      ratchet mechanism with a minimalistic design. Our artificial molecular pump
      performs work repetitively for two cycles of operation and drives rings away from
      equilibrium toward a higher local concentration. 

PMID- 25984835
TI  - Quantum oscillations in a two-dimensional electron gas in black phosphorus thin
      films.
AB  - For decades, two-dimensional electron gases (2DEG) have allowed important
      experimental discoveries and conceptual developments in condensed-matter physics.
      When combined with the unique electronic properties of two-dimensional crystals,
      they allow rich physical phenomena to be probed at the quantum level. Here, we
      create a 2DEG in black phosphorus--a recently added member of the two-dimensional
      atomic crystal family--using a gate electric field. The black phosphorus film
      hosting the 2DEG is placed on a hexagonal boron nitride substrate. The resulting
      high carrier mobility in the 2DEG allows the observation of quantum oscillations.
      The temperature and magnetic field dependence of these oscillations yields
      crucial information about the system, such as cyclotron mass and lifetime of its
      charge carriers. Our results, coupled with the fact that black phosphorus
      possesses anisotropic energy bands with a tunable, direct bandgap, distinguish
      black phosphorus 2DEG as a system with unique electronic and optoelectronic
      properties.

PMID- 25984833
TI  - Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells.
AB  - The mechanical stability and deformability of the cell nucleus are crucial to
      many biological processes, including migration, proliferation and polarization.
      In vivo, the cell nucleus is frequently subjected to deformation on a variety of
      length and time scales, but current techniques for studying nuclear mechanics do
      not provide access to subnuclear deformation in live functioning cells. Here we
      introduce arrays of vertical nanopillars as a new method for the in situ study of
      nuclear deformability and the mechanical coupling between the cell membrane and
      the nucleus in live cells. Our measurements show that nanopillar-induced nuclear
      deformation is determined by nuclear stiffness, as well as opposing effects from
      actin and intermediate filaments. Furthermore, the depth, width and curvature of
      nuclear deformation can be controlled by varying the geometry of the nanopillar
      array. Overall, vertical nanopillar arrays constitute a novel approach for non
      invasive, subcellular perturbation of nuclear mechanics and mechanotransduction
      in live cells. 

PMID- 25984836
TI  - Artificial molecular machines: Two steps uphill.

PMID- 25984838
TI  - Opioid use in pregnant women and the increase in neonatal abstinence syndrome:
      what is the cost?
AB  - OBJECTIVES: To investigate the length of stay for observation and treatment of
      neonatal abstinence syndrome (NAS), as well as the hospital costs associated with
      the medical care of affected newborns. METHODS: A retrospective chart review was
      conducted at Shands Hospital at the University of Florida, Gainesville, Florida.
      Data were collected for newborns diagnosed with NAS, including their hospital
      length of stay and the associated hospital charges, from December 1, 2008, to
      November 30, 2011. RESULTS: One hundred-sixty eligible newborns were included in
      the study. During the 3-year study period, hospital charges related to the
      diagnosis and treatment of NAS increased from $1.1 million per year to $1.8
      million per year. Compared with the cost of caring for newborns without the risk
      of NAS, an additional $4.1 million was spent in the medical care of these
      newborns. CONCLUSIONS: The costs associated with treating newborns with NAS are
      exponentially higher than the costs associated with newborns not affected with
      NAS. The societal costs associated with treatment of newborns with NAS, as well
      as infant symptomatology experienced with NAS, can be reduced by encouraging
      physicians to be proactive in screening for drug use, urging women who use
      chronic opioids to actively engage in family planning and contraception, and
      encouraging pregnant women who use opioids to seek substance treatment.

PMID- 25984837
TI  - An alignment-free method to find and visualise rearrangements between pairs of
      DNA sequences.
AB  - Species evolution is indirectly registered in their genomic structure. The
      emergence and advances in sequencing technology provided a way to access genome
      information, namely to identify and study evolutionary macro-events, as well as
      chromosome alterations for clinical purposes. This paper describes a completely
      alignment-free computational method, based on a blind unsupervised approach, to
      detect large-scale and small-scale genomic rearrangements between pairs of DNA
      sequences. To illustrate the power and usefulness of the method we give complete
      chromosomal information maps for the pairs human-chimpanzee and human-orangutan.
      The tool by means of which these results were obtained has been made publicly
      available and is described in detail. 

PMID- 25984839
TI  - Photodynamic inactivation of bacteria using novel electrogenerated porphyrin
      fullerene C60 polymeric films.
AB  - A porphyrin-fullerene C60 dyad (TCP-C60) substituted by carbazoyl groups was used
      to obtain electrogenerated polymeric films on optically transparent indium tin
      oxide (ITO) electrodes. This approach produced stable and reproducible polymers,
      holding fullerene units. The properties of this film were compared with those
      formed by layers of TCP/TCP-C60 and TCP/ZnTCP. Absorption spectra of the films
      presented the Soret and Q bands of the corresponding porphyrins. The TCP-C60 film
      produced a high photodecomposition of 2,2-(anthracene-9,10
      diyl)bis(methylmalonate), which was used to detect singlet molecular oxygen
      O2((1)Deltag) production in water. In addition, the TCP-C60 film induced the
      reduction of nitro blue tetrazolium to diformazan in the presence of NADH,
      indicating the formation of superoxide anion radical. Moreover, photooxidation of
      L-tryptophan mediated by TCP-C60 films was found in water. In biological media,
      photoinactivation of Staphylococcus aureus was evaluated depositing a drop with
      2.5 * 10(3) cells on the films. After 30 min irradiation, no colony formation was
      detected using TCP-C60 or TCP/TCP-C60 films. Furthermore, photocytotoxic activity
      was observed in cell suspensions of S. aureus and Escherichia coli. The
      irradiated TCP-C60 film produced a 4 log decrease of S. aureus survival after 30
      min. Also, a 4 log reduction of E. coli viability was obtained using the TCP-C60
      film after 60 min irradiation. Therefore, the TCP-C60 film is an interesting and
      versatile photodynamic active surface to eradicate bacteria.

PMID- 25984840
TI  - Design, synthesis and antitumor activity of triterpenoid pyrazine derivatives
      from 23-hydroxybetulinic acid.
AB  - Pyrazine-fused 23-hydroxybetulinic acid was synthesized by introducing a pyrazine
      ring between C-2 and C-3 position and further modifications were carried out by
      substitution of C-28 carboxyl group by ester and amide linkage to enhance the
      antitumor activity. The biological screening results showed that all of the
      derivatives exhibited more significant antiproliferative activity than the parent
      compound. In particular compound 12a exhibited the most potent activity with IC50
      values of 3.53 MUM, 4.42 MUM and 5.13 MUM against cell lines SF-763, B16 and
      Hela, respectively. In the preliminary mechanism study, 12a caused cell arrest in
      G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent
      manner. Furthermore, the in vivo antitumor activity of 12a was validated (tumor
      inhibitory ratio of 55.6% and 62.7%, respectively) in mice with H22 liver cancer
      and B16 melanoma. 

PMID- 25984841
TI  - Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine
      derivatives as selective metabotropic glutamate receptor 1 antagonists for the
      potential treatment of neuropathic pain.
AB  - Metabotropic glutamate receptor 1 (mGluR1) has been a prime target for drug
      discovery due to its heavy involvement in various brain disorders. Recent studies
      suggested that mGluR1 is associated with chronic pain and can serve as a
      promising target for the treatment of neuropathic pain. In an effort to develop a
      novel mGluR1 antagonist, we designed and synthesized a library of compounds with
      tetrahydrothieno[2,3-c]pyridine scaffold. Among these compounds, compound 9b and
      10b showed excellent antagonistic activity in vitro and demonstrated pain
      suppressing activity in animal models of pain. Both compounds were orally active,
      and compound 9b exhibited a favorable pharmacokinetic profile in rats. We believe
      that these compounds can provide a promising lead compound that is suitable for
      the potential treatment of neuropathic pain. 

PMID- 25984842
TI  - Exploring quercetin and luteolin derivatives as antiangiogenic agents.
AB  - The formation of new blood vessels from the pre-existing vasculature
      (angiogenesis) is a crucial stage in cancer progression and, indeed, angiogenesis
      inhibitors are now used as anticancer agents, clinically. Here we have explored
      the potential of flavonoid derivatives as antiangiogenic agents. Specifically, we
      have synthesised methoxy and 4-thio derivatives of the natural flavones quercetin
      and luteolin, two of which (4-thio quercetin and 4-thio luteolin) had never been
      previously reported. Seven of these compounds showed significant (p < 0.05)
      antiangiogenic activity in an in vitro scratch assay. Their activity ranged from
      an 86% inhibition of the vascular endothelium growth factor (VEGF)-stimulated
      migration (observed for methoxyquercetin at 10 MUM and for luteolin at 1 MUM) to
      a 36% inhibition (for thiomethoxy quercetin at 10 MUM). Western blotting studies
      showed that most (4 out of 7) compounds inhibited phosphorylation of the VEGF
      receptor-2 (VEGFR2), suggesting that the antiangiogenic activity was due to an
      interference with the VEGF/VEGFR2 pathway. Molecular modelling studies looking at
      the affinity of our compounds towards VEGFR and/or VEGF confirmed this
      hypothesis, and indeed the compound with the highest antiangiogenic activity
      (methoxyquercetin) showed the highest affinity towards VEGFR and VEGF. As reports
      from others have suggested that structurally similar compounds can elicit
      biological responses via a non-specific, promiscuous membrane perturbation,
      potential interactions of the active compounds with a model lipid bilayer were
      assessed via DSC. Luteolin and its derivatives did not perturb the model membrane
      even at concentrations 10 times higher than the biologically active concentration
      and only subtle interactions were observed for quercetin and its derivatives.
      Finally, cytotoxicity assessment of these flavonoid derivatives against MCF-7
      breast cancer cells demonstrated also a direct anticancer activity albeit at
      generally higher concentrations than those required for an antiangiogenic effect
      (10 fold higher for the methoxy analogues). Taken together these results show
      promise for flavonoid derivatives as antiangiogenic agents. 

PMID- 25984844
TI  - Metachronous hormonal syndromes in patients with pancreatic neuroendocrine
      tumors: a case-series study.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) may evolve and cause
      hormonal hypersecretion-related symptoms that were not present at the initial
      diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting,
      characteristics, and outcomes are not well-described. OBJECTIVE: To describe MHSs
      in patients with sporadic PNETs. DESIGN: Retrospective, multicenter study.
      SETTING: 4 French referral centers. PATIENTS: Patients with PNETs who developed
      MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal
      peptide, or glucagon between January 2009 and January 2014. MEASUREMENTS: Tumor
      extension, biological markers, and treatments at initial PNET diagnosis and MHS
      onset. Pathologic specimens were evaluated centrally, including Ki-67 index and
      hormone immunolabeling. RESULTS: Of 435 patients with PNETs, 15 (3.4%) were
      identified as having MHSs involving the hypersecretion of insulin (5 patients),
      vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4
      patients). Metachronous hormonal syndromes developed after a median of 55 months
      (range, 7 to 219) and in the context of PNET progression, stability, and tumor
      response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7%
      (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS
      onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of
      14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival
      after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died
      during follow-up, all due to PNETs, including 4 patients with insulin-related
      MHSs. LIMITATION: Retrospective data collection and heterogeneity of pathologic
      specimen size and origin. CONCLUSION: Metachronous hormonal syndromes were
      identified more often in the context of PNET progression and increased Ki-67
      indices. Patients with insulin-related MHSs may have decreased survival rates.
      PRIMARY FUNDING SOURCE: None.

PMID- 25984845
TI  - Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic
      Review and Meta-analysis.
AB  - BACKGROUND: Several imaging modalities are available for diagnosis of
      hepatocellular carcinoma (HCC). PURPOSE: To evaluate the test performance of
      imaging modalities for HCC. DATA SOURCES: MEDLINE (1998 to December 2014), the
      Cochrane Library Database, Scopus, and reference lists. STUDY SELECTION: Studies
      on test performance of ultrasonography, computed tomography (CT), or magnetic
      resonance imaging (MRI). DATA EXTRACTION: One investigator abstracted data, and a
      second investigator confirmed them; 2 investigators independently assessed study
      quality and strength of evidence. DATA SYNTHESIS: Few studies have evaluated
      imaging for HCC in surveillance settings. In nonsurveillance settings,
      sensitivity for detection of HCC lesions was lower for ultrasonography without
      contrast than for CT or MRI (pooled difference based on direct comparisons, 0.11
      to 0.22), and MRI was associated with higher sensitivity than CT (pooled
      difference, 0.09 [95% CI, 0.07 to 12]). For evaluation of focal liver lesions,
      there were no clear differences in sensitivity among ultrasonography with
      contrast, CT, and MRI. Specificity was generally 0.85 or higher across imaging
      modalities, but this item was not reported in many studies. Factors associated
      with lower sensitivity included use of an explanted liver reference standard, and
      smaller or more well-differentiated HCC lesions. For MRI, sensitivity was
      slightly higher for hepatic-specific than nonspecific contrast agents.
      LIMITATIONS: Only English-language articles were included, there was statistical
      heterogeneity in pooled analyses, and costs were not assessed. Most studies were
      conducted in Asia and had methodological limitations. CONCLUSION: CT and MRI are
      associated with higher sensitivity than ultrasonography without contrast for
      detection of HCC; sensitivity was higher for MRI than CT. For evaluation of focal
      liver lesions, the sensitivities of ultrasonography with contrast, CT, and MRI
      for HCC are similar. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and
      Quality. ( PROSPERO: CRD42014007016).

PMID- 25984843
TI  - Identifying women with dense breasts at high risk for interval cancer: a cohort
      study.
AB  - BACKGROUND: Twenty-one states have laws requiring that women be notified if they
      have dense breasts and that they be advised to discuss supplemental imaging with
      their provider. OBJECTIVE: To better direct discussions of supplemental imaging
      by determining which combinations of breast cancer risk and Breast Imaging
      Reporting and Data System (BI-RADS) breast density categories are associated with
      high interval cancer rates. DESIGN: Prospective cohort. SETTING: Breast Cancer
      Surveillance Consortium (BCSC) breast imaging facilities. PATIENTS: 365,426 women
      aged 40 to 74 years who had 831,455 digital screening mammography examinations.
      MEASUREMENTS: BI-RADS breast density, BCSC 5-year breast cancer risk, and
      interval cancer rate (invasive cancer <=12 months after a normal mammography
      result) per 1000 mammography examinations. High interval cancer rate was defined
      as more than 1 case per 1000 examinations. RESULTS: High interval cancer rates
      were observed for women with 5-year risk of 1.67% or greater and extremely dense
      breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24%
      of all women with dense breasts). The interval rate of advanced-stage disease was
      highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50%
      or greater and heterogeneously or extremely dense breasts (21% of all women with
      dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of
      women with heterogeneously dense breasts and 52.5% with extremely dense breasts,
      with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000
      examinations, respectively. LIMITATION: The benefit of supplemental imaging was
      not assessed. CONCLUSION: Breast density should not be the sole criterion for
      deciding whether supplemental imaging is justified because not all women with
      dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI
      RADS breast density can identify women at high risk for interval cancer to inform
      patient-provider discussions about alternative screening strategies. PRIMARY
      FUNDING SOURCE: National Cancer Institute.

PMID- 25984846
TI  - A value framework for cancer screening: advice for high-value care from the
      American College of Physicians.
AB  - Experts, professional societies, and consumer groups often recommend different
      strategies for cancer screening. These strategies vary in the intensity of their
      search for asymptomatic lesions and in their value. This article outlines a
      framework for thinking about the value of varying intensities of cancer
      screening. The authors conclude that increasing intensity beyond an optimal level
      leads to low-value screening and speculate about pressures that encourage overly
      intensive, low-value screening. 

PMID- 25984847
TI  - Screening for cancer: advice for high-value care from the American College of
      Physicians.
AB  - BACKGROUND: Cancer screening is one approach to reducing cancer-related morbidity
      and mortality rates. Screening strategies vary in intensity. Higher-intensity
      strategies are not necessarily higher value. High-value strategies provide a
      degree of benefits that clearly justifies the harms and costs incurred; low-value
      screening provides limited or no benefits to justify the harms and costs. When
      cancer screening leads to benefits, an optimal intensity of screening maximizes
      value. Some aspects of screening practices, especially overuse and underuse, are
      low value. METHODS: Screening strategies for asymptomatic, average-risk adults
      for 5 common types of cancer were evaluated by reviewing clinical guidelines and
      evidence syntheses from the American College of Physicians (ACP), U.S. Preventive
      Services Task Force, American Academy of Family Physicians, American Cancer
      Society, American Congress of Obstetricians and Gynecologists, American
      Gastroenterological Association, and American Urological Association. "High
      value" was defined as the lowest screening intensity threshold at which
      organizations agree about screening recommendations for each type of cancer and
      "low value" as agreement about not recommending overly intensive screening
      strategies. This information is supplemented with additional findings from
      randomized, controlled trials; modeling studies; and studies of costs or resource
      use, including information found in the National Cancer Institute's Physician
      Data Query and UpToDate. The ACP provides high-value care screening advice for 5
      common types of cancer; the specifics are outlined in this article. The ACP
      strongly encourages clinicians to adopt a cancer screening strategy that focuses
      on reaching all eligible persons with these high-value screening options while
      reducing overly intensive, low-value screening.

PMID- 25984849
TI  - Balloon animals, guitars, and fewer blood draws: applying strategies from
      pediatrics to the treatment of hospitalized adults.

PMID- 25984850
TI  - Celebrating the ACP Centennial: From the Annals Archive--Breast Cancer Screening.

PMID- 25984851
TI  - It's Not All About Breast Density: Risk Matters.

PMID- 25984852
TI  - You never arrive.

PMID- 25984853
TI  - Effect of Ebola progression in Liberia.

PMID- 25984854
TI  - Effect of Ebola progression in Liberia.

PMID- 25984855
TI  - Effect of Ebola progression in Liberia.

PMID- 25984856
TI  - Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD).

PMID- 25984857
TI  - Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD).

PMID- 25984858
TI  - Screening for vitamin D deficiency.

PMID- 25984859
TI  - Screening for vitamin D deficiency.

PMID- 25984860
TI  - Screening for vitamin D deficiency.

PMID- 25984861
TI  - Screening for vitamin D deficiency.

PMID- 25984862
TI  - Screening for vitamin D deficiency: is the goal disease prevention or full
      nutrient repletion?

PMID- 25984863
TI  - Screening for vitamin D deficiency: is the goal disease prevention or full
      nutrient repletion?

PMID- 25984864
TI  - Correction: Pharmacologic interventions for painful diabetic neuropathy.

PMID- 25984865
TI  - Correction: Efficacy of commercial weight-loss programs.

PMID- 25984867
TI  - Summaries for Patients. Identifying women with dense breasts at high risk for
      interval cancer.

PMID- 25984868
TI  - Summaries for Patients. A value framework for cancer screening.

PMID- 25984869
TI  - Summaries for Patients. Screening for cancer.

PMID- 25984871
TI  - ACP Journal Club. Review: Perioperative beta-blockade reduces nonfatal MI but
      increases mortality in noncardiac surgery.

PMID- 25984870
TI  - Web Exclusives. The Consult Guys--for the long haul: improving longevity after
      MI.

PMID- 25984872
TI  - ACP Journal Club. Tamoxifen for 5 years reduced 16-year risk for breast cancer in
      women at increased risk.

PMID- 25984873
TI  - ACP Journal Club. In type 1 diabetes, intensive insulin therapy for 6.5 y reduced
      mortality at 27 y compared with usual care.

PMID- 25984874
TI  - ACP Journal Club. Review: In patients having PCI, high-dose clopidogrel reduces
      major cardiac events vs standard-dose clopidogrel.

PMID- 25984875
TI  - ACP Journal Club. In acute ischemic stroke, early intraarterial treatment plus
      usual care improved functional independence.

PMID- 25984876
TI  - ACP Journal Club. In acute ischemic stroke, rapid intraarterial treatment plus
      usual care improved functional independence.

PMID- 25984877
TI  - ACP Journal Club. In ischemic stroke, early intraarterial treatment plus
      alteplase improved reperfusion and functional outcome.

PMID- 25984878
TI  - ACP Journal Club. Review: In patients with mild hypertension and no CV disease,
      BP-lowering drugs reduce stroke and mortality.

PMID- 25984879
TI  - ACP Journal Club. Review: Statins do not increase adverse cognitive effects in
      patients with or without initial cognitive impairment.

PMID- 25984880
TI  - ACP Journal Club. 6 weeks of antibiotics was noninferior to 12 weeks for clinical
      cure in pyogenic vertebral osteomyelitis.

PMID- 25984881
TI  - ACP Journal Club. Review: I.v. iron does not increase serious adverse events
      compared with other forms of iron.

PMID- 25984882
TI  - ACP Journal Club. Review: In peri- or postmenopausal women, DHEA does not improve
      symptoms and increases androgenic side effects.

PMID- 25984883
TI  - The Association Between Continuity of Care and the Overuse of Medical Procedures.
AB  - IMPORTANCE: Both the overuse of unnecessary medical procedures and poor
      continuity of care are thought to contribute to high health care spending and
      poor patient outcomes. OBJECTIVE: To investigate the association between care
      continuity and use of potentially unnecessary procedures. DESIGN, SETTING, AND
      PARTICIPANTS: Observational retrospective cohort (n = 1,208,250 patients > 65
      years) using 5% Medicare fee-for-service claims from 2008. MAIN OUTCOMES AND
      MEASURES: We evaluated continuity using the Bice-Boxerman continuity of care
      index. We measured overuse using a previously validated set of 19 potentially
      overused procedures. RESULTS: Altogether, 14.7% of patients received at least 1
      potentially overused procedure during the calendar year. For each 0.1 increase in
      the continuity score (0.4 SDs), patients had 0.93 times the odds of receiving
      overused procedures than those with lower scores (95% CI, 0.93-0.94). Higher
      continuity was significantly associated with lower odds of 9 procedures (Holm
      Bonferroni corrected P < .02 was significant: 6 of 13 diagnostic tests [with ORs,
      0.84-0.99; P  < .001] and 3 therapeutic procedures [with ORs 0.81-0.87; P
      <.001]). Conversely, higher continuity was significantly associated with
      increased overuse for 3 procedures (1 diagnostic test [OR, 1.06; P < .001], 1 of
      2 screening tests [OR, 1.05; P < .001], and the single monitoring test [OR, 1.03;
      P < .01]). CONCLUSIONS AND RELEVANCE: Increased continuity was associated with an
      overall decrease in overuse, suggesting a potential benefit of high-continuity
      care; however, the strength and direction of the association varied according to
      the specific procedure.

PMID- 25984884
TI  - Ionic Conductivity of Mesostructured Yttria-Stabilized Zirconia Thin Films with
      Cubic Pore Symmetry-On the Influence of Water on the Surface Oxygen Ion
      Transport.
AB  - Thermally stable, ordered mesoporous thin films of 8 mol % yttria-stabilized
      zirconia (YSZ) were prepared by solution-phase coassembly of chloride salt
      precursors with an amphiphilic diblock copolymer using an evaporation-induced
      self-assembly process. The resulting material is of high quality and exhibits a
      well-defined three-dimensional network of pores averaging 24 nm in diameter after
      annealing at 600  degrees C for several hours. The wall structure is
      polycrystalline, with grains in the size range of 7 to 10 nm. Using impedance
      spectroscopy, the total electrical conductivity was measured between 200 and 500 
      degrees C under ambient atmosphere as well as in dry atmosphere for oxygen
      partial pressures ranging from 1 to 10(-4) bar. Similar to bulk YSZ, a constant
      ionic conductivity is observed over the whole oxygen partial pressure range
      investigated. In dry atmosphere, the sol-gel derived films have a much higher
      conductivity, with different activation energies for low and high temperatures.
      Overall, the results indicate a strong influence of the surface on the transport
      properties in cubic fluorite-type YSZ with high surface-to-volume ratio. A
      qualitative defect model which includes surface effects (annihilation of oxygen
      vacancies as a result of water adsorption) is proposed to explain the behavior
      and sensitivity of the conductivity to variations in the surrounding atmosphere. 

PMID- 25984885
TI  - LAT Transport Inhibitors from Pittosporum venulosum Identified by NMR Fingerprint
      Analysis.
AB  - (1)H NMR fingerprints were used as the guiding principle for the isolation of
      minor compounds related to the l-type amino acid transporter inhibitors
      venulosides A (1) and B (2). Two new monoterpene glycosides, namely, venulosides
      C (3) and D (4), were isolated from a Queensland collection of the plant
      Pittosporum venulosum. Compounds 3 and 4 were found to inhibit l-leucine
      transport in LNCaP cells with IC50 values of 11.47 and 39.73 MUM, respectively.
      The venulosides are the first reported natural product inhibitors of leucine
      transport in prostate cancer cells, and the isolation of the minor compounds
      provides some early SAR information. 

PMID- 25984887
TI  - Lay understanding of forensic statistics: Evaluation of random match
      probabilities, likelihood ratios, and verbal equivalents.
AB  - Forensic scientists have come under increasing pressure to quantify the strength
      of their evidence, but it is not clear which of several possible formats for
      presenting quantitative conclusions will be easiest for lay people, such as
      jurors, to understand. This experiment examined the way that people recruited
      from Amazon's Mechanical Turk (n = 541) responded to 2 types of forensic evidence
      -a DNA comparison and a shoeprint comparison--when an expert explained the
      strength of this evidence 3 different ways: using random match probabilities
      (RMPs), likelihood ratios (LRs), or verbal equivalents of likelihood ratios
      (VEs). We found that verdicts were sensitive to the strength of DNA evidence
      regardless of how the expert explained it, but verdicts were sensitive to the
      strength of shoeprint evidence only when the expert used RMPs. The weight given
      to DNA evidence was consistent with the predictions of a Bayesian network model
      that incorporated the perceived risk of a false match from 3 causes (coincidence,
      a laboratory error, and a frame-up), but shoeprint evidence was undervalued
      relative to the same Bayesian model. Fallacious interpretations of the expert's
      testimony (consistent with the source probability error and the defense
      attorney's fallacy) were common and were associated with the weight given to the
      evidence and verdicts. The findings indicate that perceptions of forensic science
      evidence are shaped by prior beliefs and expectations as well as expert testimony
      and consequently that the best way to characterize and explain forensic evidence
      may vary across forensic disciplines.

PMID- 25984886
TI  - A dynamic transmission model with age-dependent infectiousness and reactivation
      for cytomegalovirus in the United States: Potential impact of vaccination
      strategies on congenital infection.
AB  - We present an age-structured dynamic transmission model for cytomegalovirus (CMV)
      in the United States, based on natural history and available data, primarily
      aiming to combine the available qualitative and quantitative knowledge toward
      more complex modeling frameworks to better reflect the underlying biology and
      epidemiology of the CMV infection. The model structure explicitly accounts for
      primary infections, reactivations and re-infections. Duration of infectiousness
      and likelihood of reactivation were both assumed to be age-dependent, and natural
      reduction in the re-infection risk following primary infection was included. We
      used an empirical social contact matrix (POLYMOD-based) as support for CMV
      transmission between different age groups. The baseline model reproduced well the
      age-stratified seroprevalence data (National Health and Nutrition Examination
      Survey III) used for calibration. The model was further used to explore the
      potential impact of hypothetical vaccination on reducing congenital CMV infection
      under various vaccine profiles and vaccination scenarios. Our preliminary model
      based simulations suggested that while infant vaccination may represent an
      attractive way to reduce congenital CMV infection over time, adolescent female
      vaccination with an adequate routine booster platform may, under certain
      conditions, provide an alternative. However, for such tools to be considered
      toward actual decision-making, enhanced validations based on additional studies
      and data would be further necessary. The modeling framework presented in this
      paper was designed to be sufficiently general and flexible, such that it can
      allow for further adaptations to reflect new knowledge or data that may become
      available in the future. 

PMID- 25984888
TI  - Inhumane treatment of nonhuman primate researchers.

PMID- 25984889
TI  - The cortical analysis of speech-specific temporal structure revealed by responses
      to sound quilts.
AB  - Speech contains temporal structure that the brain must analyze to enable
      linguistic processing. To investigate the neural basis of this analysis, we used
      sound quilts, stimuli constructed by shuffling segments of a natural sound,
      approximately preserving its properties on short timescales while disrupting them
      on longer scales. We generated quilts from foreign speech to eliminate language
      cues and manipulated the extent of natural acoustic structure by varying the
      segment length. Using functional magnetic resonance imaging, we identified
      bilateral regions of the superior temporal sulcus (STS) whose responses varied
      with segment length. This effect was absent in primary auditory cortex and did
      not occur for quilts made from other natural sounds or acoustically matched
      synthetic sounds, suggesting tuning to speech-specific spectrotemporal structure.
      When examined parametrically, the STS response increased with segment length up
      to ~500 ms. Our results identify a locus of speech analysis in human auditory
      cortex that is distinct from lexical, semantic or syntactic processes. 

PMID- 25984891
TI  - Overspeed HIIT in Lower-Body Positive Pressure Treadmill Improves Running
      Performance.
AB  - PURPOSE: Optimal high-intensity interval training (HIIT) regimens for running
      performance are unknown, although most protocols result in some benefit to key
      performance factors (running economy (RE), anaerobic threshold (AT), or maximal
      oxygen uptake (VO2max)). Lower-body positive pressure (LBPP) treadmills offer the
      unique possibility to partially unload runners and reach supramaximal speeds. We
      studied the use of LBPP to test an overspeed HIIT protocol in trained runners.
      METHODS: Eleven trained runners (35 +/- 8 yr, VO2max, 55.7 +/- 6.4 mL.kg-1.min-1)
      were randomized to an LBPP (n = 6) or a regular treadmill (CON, n = 5), eight
      sessions over 4 wk of HIIT program. Four to five intervals were run at 100% of
      velocity at VO2max (vVO2max) during 60% of time to exhaustion at vVO2max (Tlim)
      with a 1:1 work:recovery ratio. Performance outcomes were 2-mile track time
      trial, VO2max, vVO2max, vAT, Tlim, and RE. LBPP sessions were carried out at 90%
      body weight. RESULTS: Group-time effects were present for vVO2max (CON, 17.5 vs.
      18.3, P = 0.03; LBPP, 19.7 vs. 22.3 km.h-1; P < 0.001) and Tlim (CON, 307.0 vs.
      404.4 s, P = 0.28; LBPP, 444.5 vs. 855.5, P < 0.001). Simple main effects for
      time were present for field performance (CON, -18; LBPP, -25 s; P = 0.002),
      VO2max (CON, 57.6 vs. 59.6; LBPP, 54.1 vs. 55.1 mL.kg-1.min-1; P = 0.04) and
      submaximal HR (157.7 vs. 154.3 and 151.4 vs. 148.5 bpm; P = 0.002). RE was
      unchanged. CONCLUSIONS: A 4-wk HIIT protocol at 100% vVO2max improves field
      performance, vVO2max, VO2max and submaximal HR in trained runners. Improvements
      are similar if intervals are run on a regular treadmill or at higher speeds on a
      LPBB treadmill with 10% body weight reduction. LBPP could provide an alternative
      for taxing HIIT sessions.

PMID- 25984890
TI  - Social signals of safety and risk confer utility and have asymmetric effects on
      observers' choices.
AB  - Individuals' risk attitudes are known to guide choices about uncertain options.
      However, in the presence of others' decisions, these choices can be swayed and
      manifest as riskier or safer behavior than one would express alone. To test the
      mechanisms underlying effective social 'nudges' in human decision-making, we used
      functional neuroimaging and a task in which participants made choices about
      gambles alone and after observing others' selections. Against three alternative
      explanations, we found that observing others' choices of gambles increased the
      subjective value (utility) of those gambles for the observer. This 'other
      conferred utility' was encoded in ventromedial prefrontal cortex, and these
      neural signals predicted conformity. We further identified a parametric
      interaction with individual risk preferences in anterior cingulate cortex and
      insula. These data provide a neuromechanistic account of how information from
      others is integrated with individual preferences that may explain preference
      congruent susceptibility to social signals of safety and risk. 

PMID- 25984892
TI  - Using GPS, GIS, and Accelerometer Data to Predict Transportation Modes.
AB  - INTRODUCTION: Active transportation is a substantial source of physical activity,
      which has a positive influence on many health outcomes. A survey of
      transportation modes for each trip is challenging, time-consuming, and requires
      substantial financial investments. This study proposes a passive collection
      method and the prediction of modes at the trip level using random forests.
      METHODS: The RECORD GPS study collected real-life trip data from 236 participants
      over 7 d, including the transportation mode, global positioning system,
      geographical information systems, and accelerometer data. A prediction model of
      transportation modes was constructed using the random forests method. Finally, we
      investigated the performance of models on the basis of a limited number of
      participants/trips to predict transportation modes for a large number of trips.
      RESULTS: The full model had a correct prediction rate of 90%. A simpler model of
      global positioning system explanatory variables combined with geographical
      information systems variables performed nearly as well. Relatively good
      predictions could be made using a model based on the 991 trips of the first 30
      participants. CONCLUSIONS: This study uses real-life data from a large sample set
      to test a method for predicting transportation modes at the trip level, thereby
      providing a useful complement to time unit-level prediction methods. By enabling
      predictions on the basis of a limited number of observations, this method may
      decrease the workload for participants/researchers and provide relevant trip
      level data to investigate relations between transportation and health.

PMID- 25984894
TI  - Time to Empower People With Stroke.

PMID- 25984895
TI  - ESEM-EDS: In vivo characterization of the Ni hyperaccumulator Noccaea
      caerulescens.
AB  - Environmental scanning electron microscopy (ESEM) permits to analyze samples in
      their native-hydrated state, allowing a broad spectrum of biological
      applications. In this study, ESEM equipped with energy dispersive X-ray
      spectrometer (EDS) was used as a fast method to analyze tissue morphology and to
      investigate metal distribution in the Ni hyperaccumulator Noccaea caerulescens,
      an established model to study the adaptation of plants to metalliferous soils.
      The low vacuum and wet mode operative conditions required the proper choice of
      experimental parameters both for morphological and compositional characterization
      of plant tissues. The calibration strategy for semi-quantitative analysis
      involved the use of Ni fortified agar as standard and signal normalization
      respect to endogenous carbon, chosen as internal standard. The obtained results
      are in accordance with present literature, showing a preferential Ni distribution
      in the epidermal cells respect to near the stomata for leaves and in the
      cotyledon epidermidis respect to cotyledon parenchyma area for seeds. Thanks to
      the absence of any time consuming sample treatment steps, ESEM-EDS technique can
      be proposed as valid strategy for in vivo high-throughput analysis of plant
      tissues and for a rapid screening and identification of other hyperaccumulator
      plants in a selected contaminated area. 

PMID- 25984893
TI  - The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition
      induced macroautophagy in mammalian cells.
AB  - By monitoring the fragmentation of a GST-BHMT (a protein fusion of glutathionine
      S-transferase N-terminal to betaine-homocysteine S-methyltransferase) reporter in
      lysosomes, the GST-BHMT assay has previously been established as an endpoint,
      cargo-based assay for starvation-induced autophagy that is largely nonselective.
      Here, we demonstrate that under nutrient-rich conditions, proteasome inhibition
      by either pharmaceutical or genetic manipulations induces similar autophagy
      dependent GST-BHMT processing. However, mechanistically this proteasome
      inhibition-induced autophagy is different from that induced by starvation as it
      does not rely on regulation by MTOR (mechanistic target of rapamycin
      [serine/threonine kinase]) and PRKAA/AMPK (protein kinase, AMP-activated, alpha
      catalytic subunit), the upstream central sensors of cellular nutrition and energy
      status, but requires the presence of the cargo receptors SQSTM1/p62 (sequestosome
      1) and NBR1 (neighbor of BRCA1 gene 1) that are normally involved in the
      selective autophagy pathway. Further, it depends on ER (endoplasmic reticulum)
      stress signaling, in particular ERN1/IRE1 (endoplasmic reticulum to nucleus
      signaling 1) and its main downstream effector MAPK8/JNK1 (mitogen-activated
      protein kinase 8), but not XBP1 (X-box binding protein 1), by regulating the
      phosphorylation-dependent disassociation of BCL2 (B-cell CLL/lymphoma 2) from
      BECN1 (Beclin 1, autophagy related). Moreover, the multimerization domain of GST
      BHMT is required for its processing in response to proteasome inhibition, in
      contrast to its dispensable role in starvation-induced processing. Together,
      these findings support a model in which under nutrient-rich conditions,
      proteasome inactivation induces autophagy-dependent processing of the GST-BHMT
      reporter through a distinct mechanism that bears notable similarity with the
      yeast Cvt (cytoplasm-to-vacuole targeting) pathway, and suggest the GST-BHMT
      reporter might be employed as a convenient assay to study selective
      macroautophagy in mammalian cells. 

PMID- 25984896
TI  - General practitioners' judgement of chronic heart failure in the oldest old:
      Insights from the BELFRAIL study.
AB  - BACKGROUND AND OBJECTIVES: Conflicting evidence exists about the value of general
      practitioners' (GPs') diagnoses of chronic heart failure (CHF), especially in
      older persons. Therefore, the relationship between GPs' judgement of CHF and
      objective cardiac abnormalities and their respective prognostic value for 5-year
      mortality in patients aged 80 and older was studied. METHODS AND RESULTS: These
      analyses were embedded within the prospective, population-based BELFRAIL study.
      At baseline, 525 patients (mean age 85 +/- 3.7 years, 37% men) were clinically
      assessed by their GPs, had NT-proBNP levels determined and received a detailed
      echocardiography at home. GPs were asked to judge the presence of CHF and to list
      their arguments in favour or against CHF. Cause-specific mortality was collected
      until 5.2 +/- 0.25 years after baseline. GPs suspected CHF in 154 patients (29%).
      The prevalence of objective cardiac abnormalities was 35% (n=183). GPs' judgement
      predicted objective cardiac abnormalities inaccurately (sensitivity 45% (95% CI
      38-53), specificity 79% (95% CI 75-83)). However, both objective cardiac
      abnormalities and GPs' diagnoses of CHF were good predictors of 5-year mortality
      (HR 2.1 (95% CI 1.6-2.7) vs 1.7 (95% CI 1.3-2.3), respectively). Furthermore, the
      presence of objective cardiac abnormalities was not significantly better than
      GPs' judgement in identifying patients at risk for mortality, although a trend
      for better cardiovascular mortality risk classification was noted (NRI 10% (95%
      CI -2 to 21%), P=0.13). CONCLUSIONS: Although GPs' judgement of CHF and objective
      cardiac abnormalities correlated poorly, the validity of GPs' clinical judgement
      for mortality risk stratification was demonstrated.

PMID- 25984897
TI  - An alternative method of percutaneous mitral valvuloplasty. Matching
      electrophysiology with interventional cardiology techniques.

PMID- 25984898
TI  - Association between cumulative social risk and ideal cardiovascular health in US
      adults: NHANES 1999-2006.
AB  - BACKGROUND: The American Heart Association developed the Life's Simple 7 metric
      for defining cardiovascular health. Little is known about the association of co
      occurring social risk factors on ideal cardiovascular health. METHODS: Using data
      on 11,467 adults aged >=25 years from the National Health and Nutrition
      Examination Survey 1999-2006, we examined the association between cumulative
      social risk and ideal cardiovascular health in US adults. A cumulative risk score
      (range 0 to 3 or 4) was created by summing four social risk factors (low family
      income, low education level, minority race, and single-living status). Ideal
      levels for each component in Life's Simple 7 (blood pressure, cholesterol,
      glucose, BMI, smoking, physical activity, and diet) were used to create an ideal
      Life's Simple 7 score [0-1 (low), 2, 3, 4, and 5-7 (high)]. RESULTS: Adults with
      low income (odds ratio [OR]=0.30 [95% CI 0.23-0.39]), low education [0.22 (0.16
      0.28)], who are non-white (0.44 [0.36-0.54]) and single-living [0.79 (0.67-0.95)]
      were less likely to have 5-7 versus 0 ideal Life's Simple 7 scores after
      adjustment for age and sex. Adults were less likely to attain 5-7 versus 0 ideal
      Life's Simple 7 scores as exposure to the number of social risk factors increased
      [OR (95% CI) of 0.58 (0.49-0.68); 0.27 (0.21-0.35); and 0.19 (0.14-0.27) for
      cumulative social risk scores of 1, 2, and 3 or 4, respectively, each versus 0].
      CONCLUSIONS: US adults with an increasing number of socially risk factors, were
      progressively less likely to attain ideal levels of cardiovascular health
      factors.

PMID- 25984899
TI  - Association between arrhythmogenic cardiomyopathy and Brugada syndrome - The
      influence of novel electrocardiographic features of Brugada syndrome.

PMID- 25984900
TI  - Combination of radiofrequency and intralesional steroids in the treatment of
      keloids: a pilot study.
AB  - BACKGROUND: None of therapeutic options for the treatment of keloids has been
      found completely effective and satisfactory. A combination approach is the best
      modality. OBJECTIVE: To assess the clinical safety and efficacy of radiofrequency
      (RF) followed by intralesional (IL) steroid injection in keloids. MATERIALS AND
      METHODS: This pilot study included 18 patients who were suffering from keloids.
      All patients were subjected to 3 to 4 sessions of RF followed by IL steroid
      injection. Assessment of the scar volume and both objective and subjective
      parameters has been performed before and after completion of the sessions.
      RESULTS: There was a significant reduction of volume of all lesions in all
      patients after a total of 3 to 4 sessions (p = .001), with a mean volume
      reduction of 95.4%. There was a significant reduction of keloid pliability,
      height, and erythema compared with baseline (p < .001). Patients reported a
      significant reduction of their subjective symptoms compared with baseline (p <
      .001). No pain, infection, nor bleeding were reported after the RF procedure.
      CONCLUSION: Radiofrequency tissue volume reduction combined with IL steroid is an
      effective treatment modality for keloids. It is an easy procedure with acceptable
      cosmetic outcome and less rate of recurrence.

PMID- 25984902
TI  - Voriconazole-induced multiple squamous cell carcinomas in a patient with chronic
      lymphocytic leukemia.

PMID- 25984901
TI  - Role of antiseptics in the prevention of surgical site infections.
AB  - BACKGROUND: Antiseptics are chemical agents used to reduce the microbial
      population on the surface of the skin and are used in nearly every surgical
      procedure today. Despite this, there are currently no definitive guidelines on
      surgical preoperative antisepsis that indicate a specific regimen based on
      demonstration of superior efficacy. OBJECTIVE: This review serves to examine
      preoperative antisepsis, including cutaneous bacteriology, preoperative hair
      removal, preoperative decolonization, surgical attire, and the antiseptic agents
      themselves. MATERIALS AND METHODS: A review of the literature on surgical
      antiseptics was performed. RESULTS: Although numerous studies have demonstrated
      differences in bacterial colonization rates, few well-controlled investigations
      have demonstrated superiority of a given regimen. The alcohol-based iodophor and
      chlorhexidine products seem to exhibit greater efficacy than their aqueous
      counterparts. CONCLUSION: More randomized controlled trials will be needed to
      determine if any specific regimen is most effective. At this point in time,
      product usage should be based on specific attributes relating to the products,
      such as iodophors around the eyes and/or ears to avoid irritation and aqueous
      based solutions in hair bearing areas because of concern for flammability.
      Ultimately, it is up to the individual surgeon to tailor the optimal antiseptic
      regimen for their specific scope of practice.

PMID- 25984903
TI  - Topical oxymetazoline hydrochloride 0.05% as a strategy to reduce intraoperative
      wound oozing in Mohs micrographic surgery.

PMID- 25984904
TI  - Correction of pincer nail deformities using a modified double Z-plasty.
AB  - BACKGROUND: Pincer nail is a deformity characterized by excessive transverse
      curvature of the nail plate that increases distally for which many conservative
      and surgical corrective modalities have been recommended. OBJECTIVE: The purpose
      of this study is to investigate the outcomes and safety of modified double Z
      plasty in the management of symptomatic pincer nail. MATERIALS AND METHODS:
      Modified double Z-plasty has been performed on 20 great toes in 12 patients from
      January 2008 to December 2013. The mean age of patients was 43 (range: 20-65)
      years. Three men and 9 women were enrolled. Visual analogue scale (VAS) score for
      pain, transverse angle, and width indices were investigated at the initial and
      the last follow-up. The average follow-up period was 2.4 years. RESULTS: All
      parameters showed significant improvement after surgery. Between the initial and
      last follow-up, the mean VAS score fell from 7.4 to 0.3, the mean transverse
      angle improved from 50 to 166 degrees , and the mean width index improved from
      65.4% to 97%. In all patients, the deformity was successfully eliminated with no
      recurrences. No complications were identified. CONCLUSION: Modified double Z
      plasty provides a long-standing effective treatment for pincer nail deformity
      with an excellent esthetic result.

PMID- 25984905
TI  - Eccrine Porocarcinoma Treated by Mohs Micrographic Surgery: Over 6-Year Follow-up
      of 12 Cases and Literature Review.
AB  - BACKGROUND: Eccrine porocarcinoma (EPC) has a poor prognosis after standard wide
      local excision (WLE), with 20% local recurrence, 20% regional and 12% distant
      metastatic rates. Mohs micrographic surgery (MMS) has been used as a promising
      treatment. OBJECTIVE: To review the use of MMS for EPC and assess treatment
      outcomes. MATERIALS AND METHODS: This was a retrospective case series of 12 EPC
      patients treated by MMS between 1984 and 2013 in the institution. Furthermore, a
      literature review revealed an additional 17 cases of EPC managed by MMS. RESULTS:
      Of 29 cases of EPC treated by MMS, outcome was established in 27 cases. The
      patients had a significantly longer mean follow-up period of 6 years (range, 4
      206 months), as compared with 19 months (range, 2-48 months) in reported cases.
      Two patients had regional lymph node metastasis after MMS. The regional
      metastatic rates to lymph nodes were 7% (2/27). There was no local recurrence,
      distant metastasis, or disease-specific death in the 27 cases studied.
      CONCLUSION: To the best of the authors' knowledge, this is the single largest
      case series of EPCs treated by MMS and the authors' data demonstrated that MMS
      may be superior to the standard WLE.

PMID- 25984906
TI  - Utilization of Mohs micrographic surgery in a patient with onychomatricoma.

PMID- 25984908
TI  - Titanium(IV) catalysts with ancillary imino-spiroketonato ligands: synthesis,
      structure and olefin polymerization.
AB  - New titanium(IV) complexes having two bidentate beta-iminoethyl-spiro[4,5]decan-6
      onato ligands with various N-aryl substituents have been synthesized. X-ray
      crystal structure analysis reveals that these titanium complexes all exhibit a C2
      symmetric conformation with a distorted octahedral geometry, although the
      specific orientation of the ligands around the titanium center varies with the
      identity of the N-aryl moiety. Upon activation with methylaluminoxane (MAO),
      these complexes catalyze the polymerization of ethylene and propylene. In the
      case of ethylene, most complexes exhibit the characteristics of a living
      polymerization between 0  degrees C and 25  degrees C, producing polyethylenes
      with narrow molecular weight distributions and number average molecular weights
      up to 100,000 g/mol. Depending on the N-aryl substituents, polymerizations of
      propylene result in products with tacticity ranging from slightly syndiotactic to
      slightly isotactic.

PMID- 25984907
TI  - Unraveling novel TF-miRNA regulatory crosstalk in metastasis of Soft Tissue
      Sarcoma.
AB  - Cancer metastasis is a disease of extreme clinical relevance, as it is
      responsible for more than 90% of cancer-associated mortality. The molecular
      mechanism and critical regulators involved in this complex multi-stage process of
      metastasis is poorly deciphered in soft tissue sarcomas (STS), a heterogeneous
      group of rare tumors with high metastatic potential. Therefore, we aimed at
      identifying miRNA and transcription factor (TF) regulatory networks and paths in
      STS metastasis. We integrated mRNA and miRNA expression profiles with curated
      regulations (TF->gene, TF->miRNA, miRNA->gene) from different databases and
      constructed a potentially active regulatory sub-network in STS metastasis. From
      functional and topological analysis, we found nine novel regulators of Notch
      signaling sub-network which are conjectured to play critical role in metastasis
      of STS. This illustrated that the sub-network is promising for identification of
      critical regulators. Further analysis deploying our developed tool 'RiNAcyc' and
      computing coverage ratio of known STS associated genes and miRNAs identified a 15
      node active path. This potential path highlights the crucial role of BMP2, hsa
      miR-24, AP2 and MYC as the up-stream regulators of the path and hsa-miR-215 and
      TYMS as potential indicator of chemotherapeutic benefit in STS metastasis. 

PMID- 25984909
TI  - Predictive testing for Alzheimer's disease: suicidal ideation in healthy
      participants.

PMID- 25984910
TI  - Pathogenicity of Isolates of Serratia Marcescens towards Larvae of the Scarab
      Phyllophaga Blanchardi (Coleoptera).
AB  - Serratia marcescens is a Gram negative bacterium (Enterobacteriaceae) often
      associated with infection of insects. In order to find pathogenic bacteria with
      the potential to control scarab larvae, several bacterial strains were isolated
      from the hemocoel of diseased Phyllophaga spp (Coleoptera:Scarabaeidae) larvae
      collected from cornfields in Mexico. Five isolates were identified as Serratia
      marcescens by 16S rRNA gene sequencing and biochemical tests. Oral and injection
      bioassays using healthy Phyllophaga blanchardi larvae fed with the S. marcescens
      isolates showed different degrees of antifeeding effect and mortality. No
      insecticidal activity was observed for Spodoptera frugiperda larvae (Lepidoptera:
      Noctuidae) by oral inoculation. S. marcescens (Sm81) cell-free culture
      supernatant caused significant antifeeding effect and mortality to P. blanchardi
      larvae by oral bioassay and also mortality by injection bioassay. Heat treated
      culture broths lost the ability to cause disease symptoms, suggesting the
      involvement of proteins in the toxic activity. A protein of 50.2 kDa was purified
      from the cell-free broth and showed insecticidal activity by injection bioassay
      towards P. blanchardi. Analysis of the insecticidal protein by tandem- mass
      spectrometry (LC-MS/MS) showed similarity to a Serralysin-like protein from S.
      marcescens spp. This insecticidal protein could have applications in agricultural
      biotechnology. 

PMID- 25984912
TI  - Unexpected buckled structures and tunable electronic properties in arsenic
      nanosheets: insights from first-principles calculations.
AB  - Using dispersion-corrected density functional theory calculations, we investigate
      the structural and electronic properties of arsenic (As) nanosheet, which is a
      cousin of phosphorene. We find that the black-phosphorus like structure is
      dynamically unstable for As, which has an out-of-plane soft mode from its flat As
      zigzag lines. Hence different from phosphorene, the stable As monolayer possesses
      a unique buckling along the zigzag direction, which leads to a surface
      corrugation of 0.20 A and a robust dynamic stability. The zigzag buckling alters
      the band feature of As nanosheet, transforming it from an indirect band gap
      semiconductor to a direct one for the buckled structure. Strain engineering can
      further tune the surface corrugation and band structure of As nanosheet, for
      which the direct or indirect gap feature can be switched by the zigzag
      directional strains, while the strains along armchair direction could modulate
      the band gap and induce a metallic behaviour. Prominent anisotropic Dirac-like
      electronic structures and orientation-dependent elastic behaviours with a
      remarkable negative Poisson ratio are both found in the As nanosheets, enabling
      the system promising applications for nano-electrics and devices.

PMID- 25984913
TI  - A Family of Co(II)Co(III)3 Single-Ion Magnets with Zero-Field Slow Magnetic
      Relaxation: Fine Tuning of Energy Barrier by Remote Substituent and Counter
      Cation.
AB  - The synthesis, structures, and magnetic properties of a family of air-stable star
      shaped Co(II)Co(III)3 complexes were investigated. These complexes contain only
      one paramagnetic Co(II) ion with the approximate D3 coordination environment in
      the center and three diamagnetic Co(III) ions in the peripheral. Magnetic studies
      show their slow magnetic relaxation in the absence of an applied dc field, which
      is characteristic behavior of single-molecule magnets (SMMs), caused by the
      individual Co(II) ion with approximate D3 symmetry in the center. Most
      importantly, it was demonstrated that the anisotropy energy barrier can be finely
      tuned by the periphery substituent of the ligand and the countercation. The
      anisotropy energy barrier can be increased significantly from 38 K to 147 K. 

PMID- 25984911
TI  - Global occurrence and emission of rotaviruses to surface waters.
AB  - Group A rotaviruses (RV) are the major cause of acute gastroenteritis in infants
      and young children globally. Waterborne transmission of RV and the presence of RV
      in water sources are of major public health importance. In this paper, we present
      the Global Waterborne Pathogen model for RV (GloWPa-Rota model) to estimate the
      global distribution of RV emissions to surface water. To our knowledge, this is
      the first model to do so. We review the literature to estimate three RV specific
      variables for the model: incidence, excretion rate and removal during wastewater
      treatment. We estimate total global RV emissions to be 2 * 1018 viral
      particles/grid/year, of which 87% is produced by the urban population. Hotspot
      regions with high RV emissions are urban areas in densely populated parts of the
      world, such as Bangladesh and Nigeria, while low emissions are found in rural
      areas in North Russia and the Australian desert. Even for industrialized regions
      with high population density and without tertiary treatment, such as the UK,
      substantial emissions are estimated. Modeling exercises like the one presented in
      this paper provide unique opportunities to further study these emissions to
      surface water, their sources and scenarios for improved management. 

PMID- 25984914
TI  - Effects of Salt on the Stability of a G-Quadruplex from the Human c-MYC Promoter.
AB  - In an atmosphere of potassium ions, a modified c-MYC NHE III1 sequence with two G
      to-T mutations (MYC22-G14T/G23T) forms a highly stable parallel-stranded G
      quadruplex. The G-quadruplex exhibits a steady increase in its melting
      temperature, T(M), with an increase in the concentration of the stabilizing
      cation K(+). On the other hand, an increase in the concentration of
      nonstabilizing Cs(+) or TMA(+) cations at a constant concentration of K(+) causes
      a sharp decline in T(M) followed by a leveling off at ~200 mM Cs(+) or TMA(+). At
      51  degrees C and 600 MUM K(+), an increase in Cs(+) concentration from 0 to 800
      mM leads to a complete unfolding of the G-quadruplex. These observations are
      consistent with the picture in which more counterions accumulate in the vicinity
      of the unfolded state of MYC22-G14T/G23T (nonspecific ion binding) than in that
      of the G-quadruplex state. We estimate that the unfolded state condenses one
      extra counterion compared to the G-quadruplex state. Taken together with our
      earlier results, our data suggest that sodium or potassium cations sequestered
      inside the central cavity stabilize the G-quadruplex conformation acting as
      specifically bound ligands. Nonspecifically bound (condensed) counterions may
      slightly stabilize, exert no influence (human telomeric G-quadruplexes), or
      strongly destabilize (MYC22-G14T/G23T) the G-quadruplex conformation. We offer a
      structural rationalization for the enhanced thermal stability of the MYC22
      G14T/G23T G-quadruplex.

PMID- 25984915
TI  - Glycosylation Modulates Human CD2-CD58 Adhesion via Conformational Adjustment.
AB  - Human CD2 is a transmembrane cell surface glycoprotein found on T lymphocytes and
      natural killer cells and plays important roles in immune recognition. The
      interaction between human CD2 and its counter receptor CD58 facilitates surface
      adhesion between helper T lymphocytes and antigen presenting cells as well as
      between cytolytic effectors and target cells. In this study, the molecular effect
      of glycosylation of CD2 on the structure and dynamics of the CD2-CD58 adhesion
      complex were examined via MD simulation to help understand the fundamental
      mechanism of glycosylation that controls CD2-CD58 adhesion. The present result
      and detailed analysis revealed that the binding interaction of human CD2-CD58 is
      dominated by three hot spots that form a binding triangle whose topology is
      critical for stable binding of CD2-CD58. Our study found that the conformation of
      human CD2, represented by the topology of this binding triangle, is significantly
      adjusted and steered by glycosylation toward a particular conformation that
      energetically stabilizes the CD2-CD58 complex. Thus, the fundamental mechanism of
      glycosylation of human CD2 is to promote CD2-CD58 binding by conformational
      adjustment of CD2. The current result and explanation are in excellent agreement
      with previous experiments and help elucidate the dynamical mechanism of
      glycosylation of human CD2. 

PMID- 25984917
TI  - Perception of fore-and-aft whole-body vibration intensity measured by two
      methods.
AB  - This experimental study investigated the perception of fore-and-aft whole-body
      vibration intensity using cross-modality matching (CM) and magnitude estimation
      (ME) methods. Thirteen subjects were seated on a rigid seat without a backrest
      and exposed to sinusoidal stimuli from 0.8 to 12.5 Hz and 0.4 to 1.6 ms(-2)
      r.m.s. The Stevens exponents did not significantly depend on vibration frequency
      or the measurement method. The ME frequency weightings depended significantly on
      vibration frequency, but the CM weightings did not. Using the CM and ME
      weightings would result in higher weighted exposures than those calculated using
      the ISO (2631-1, 1997) Wd. Compared with ISO Wk, the CM and ME-weighted exposures
      would be greater at 1.6 Hz and lesser above that frequency. The CM and ME
      frequency weightings based on the median ratings for the reference vibration
      condition did not differ significantly. The lack of a method effect for
      weightings and for Stevens exponents suggests that the findings from the two
      methods are comparable. PRACTITIONER SUMMARY: Frequency weighting curves for
      seated subjects for x-axis whole-body vibration were derived from an experiment
      using two different measurement methods and were compared with the Wd and Wk
      weighting curves in ISO 2631-1 (1997).

PMID- 25984916
TI  - mHealth in Urology: A Review of Experts' Involvement in App Development.
AB  - INTRODUCTION: Smartphones are increasingly playing a role in healthcare and
      previous studies assessing medical applications (apps) have raised concerns about
      lack of expert involvement and low content accuracy. However, there are no such
      studies in Urology. We reviewed Urology apps with the aim of assessing the level
      of participation of healthcare professionals (HCP) and scientific Urology
      associations in their development. MATERIAL AND METHODS: A systematic search was
      performed on PubMed, Apple's App Store and Google's Play Store, for Urology apps,
      available in English. Apps were reviewed by three graders to determine the app's
      platform, target customer, developer, app type, app category, price and the
      participation of a HCP or a scientific Urology association in the development.
      RESULTS: The search yielded 372 apps, of which 150 were specific for Urology. A
      fifth of all apps had no HCP involvement (20.7%) and only a third had been
      developed with a scientific Urology association (34.7%). The lowest percentage of
      HCP (13.4%) and urological association (1.9%) involvement was in apps designed
      for the general population. Furthermore, there was no contribution from an
      Urology society in "Electronic Medical Record" nor in "Patient Information" apps.
      A limitation of the study is that only Android and iOS apps were reviewed.
      CONCLUSIONS: Despite the increasing Mobile Health (mHealth) market, this is the
      first study that demonstrates the lack of expert participation in the design of
      Urology apps, particularly in apps designed for the general public. Until clear
      regulation is enforced, the urological community should help regulate app
      development. Maintaining a register of certified apps or issuing an official
      scientific seal of approval could improve overall app quality. We propose that
      urologists become stakeholders in mHealth, shaping future app design and
      promoting peer-review app validation.

PMID- 25984919
TI  - Habitability of waterworlds: runaway greenhouses, atmospheric expansion, and
      multiple climate states of pure water atmospheres.
AB  - There are four different stable climate states for pure water atmospheres, as
      might exist on so-called "waterworlds." I map these as a function of solar
      constant for planets ranging in size from Mars-sized to 10 Earth-mass. The states
      are as follows: globally ice covered (Ts ? 245 K), cold and damp (270 ? Ts ? 290
      K), hot and moist (350 ? Ts ? 550 K), and very hot and dry (Tsx2A86;900 K). No
      stable climate exists for 290 ? T s ? 350 K or 550 ? Ts ? 900 K. The union of hot
      moist and cold damp climates describes the liquid water habitable zone, the width
      and location of which depends on planet mass. At each solar constant, two or
      three different climate states are stable. This is a consequence of strong
      nonlinearities in both thermal emission and the net absorption of sunlight.
      Across the range of planet sizes, I account for the atmospheres expanding to high
      altitudes as they warm. The emitting and absorbing surfaces (optical depth of
      unity) move to high altitude, making their area larger than the planet surface,
      so more thermal radiation is emitted and more sunlight absorbed (the former
      dominates). The atmospheres of small planets expand more due to weaker gravity;
      the effective runaway greenhouse threshold is about 35 W m(-2) higher for Mars,
      10 W m(-2) higher for Earth or Venus, but only a few W m(-2) higher for a 10
      Earth-mass planet. There is an underlying (expansion-neglected) trend of
      increasing runaway greenhouse threshold with planetary size (40 W m(-2) higher
      for a 10 Earth-mass planet than for Mars). Summing these opposing trends means
      that Venus-sized (or slightly smaller) planets are most susceptible to a runaway
      greenhouse. The habitable zone for pure water atmospheres is very narrow, with an
      insolation range of 0.07 times the solar constant. A wider habitable zone
      requires background gas and greenhouse gas: N2 and CO2 on Earth, which are
      biologically controlled. Thus, habitability depends on inhabitance.

PMID- 25984921
TI  - In search of future earths: assessing the possibility of finding Earth analogues
      in the later stages of their habitable lifetimes.
AB  - Earth will become uninhabitable within 2-3 Gyr as a result of the increasing
      luminosity of the Sun changing the boundaries of the habitable zone (HZ).
      Predictions about the future of habitable conditions on Earth include declining
      species diversity and habitat extent, ocean loss, and changes to geochemical
      cycles. Testing these predictions is difficult, but the discovery of a planet
      that is an analogue to future Earth could provide the means to test them. This
      planet would need to have an Earth-like biosphere history and to be approaching
      the inner edge of the HZ at present. Here, we assess the possibility of finding
      such a planet and discuss the benefits of analyzing older Earths. Finding an old
      Earth analogue in nearby star systems would be ideal, because this would allow
      for atmospheric characterization. Hence, as an illustrative example, G stars
      within 10 pc of the Sun are assessed as potential old-Earth-analog hosts. Six of
      these represent good potential hosts. For each system, a hypothetical Earth
      analogue is placed at locations within the continuously habitable zone (CHZ) that
      would allow enough time for Earth-like biosphere development. Surface temperature
      evolution over the host star's main sequence lifetime (assessed by using a simple
      climate model) is used to determine whether the planet would be in the right
      stage of its late-habitable lifetime to exhibit detectable biosignatures. The
      best candidate, in terms of the chances of planet formation in the CHZ and of
      biosignature detection, is 61 Virginis. However, planet formation studies suggest
      that only a small fraction (0.36%) of G stars in the solar neighborhood could
      host an old-Earth analogue. If the development of Earth-like biospheres is rare,
      requiring a sequence of low-probability events to occur, biosphere evolution
      models suggest they are rarer still, with only thousands being present in the
      Galaxy as a whole.

PMID- 25984920
TI  - The production of methane, hydrogen, and organic compounds in ultramafic-hosted
      hydrothermal vents of the Mid-Atlantic Ridge.
AB  - Both hydrogen and methane are consistently discharged in large quantities in
      hydrothermal fluids issued from ultramafic-hosted hydrothermal fields discovered
      along the Mid-Atlantic Ridge. Considering the vast number of these fields
      discovered or inferred, hydrothermal fluxes represent a significant input of H2
      and CH4 to the ocean. Although there are lines of evidence of their abiogenic
      formation from stable C and H isotope results, laboratory experiments, and
      thermodynamic data, neither their origin nor the reaction pathways generating
      these gases have been fully constrained yet. Organic compounds detected in the
      fluids may also be derived from abiotic reactions. Although thermodynamics are
      favorable and extensive experimental work has been done on Fischer-Tropsch-type
      reactions, for instance, nothing is clear yet about their origin and formation
      mechanism from actual data. Since chemolithotrophic microbial communities
      commonly colonize hydrothermal vents, biogenic and thermogenic processes are
      likely to contribute to the production of H2, CH4, and other organic compounds.
      There seems to be a consensus toward a mixed origin (both sources and processes)
      that is consistent with the ambiguous nature of the isotopic data. But the
      question that remains is, to what proportions? More systematic experiments as
      well as integrated geochemical approaches are needed to disentangle hydrothermal
      geochemistry. This understanding is of prime importance considering the
      implications of hydrothermal H2, CH4, and organic compounds for the ocean global
      budget, global cycles, and the origin of life.

PMID- 25984922
TI  - Nazarov reactions intercepted by (4 + 3) cycloadditions with oxygen-substituted
      dienes.
AB  - The oxyallyl cation intermediate from the Lewis acid mediated Nazarov reaction of
      an allenyl vinyl ketone was intercepted by acyclic, 2-silyloxy-substituted
      butadienes by highly regioselective (4 + 3) cycloadditions. Stereoselectivity was
      often modest, but in some instances steric interactions were responsible for high
      selectivity. The results are consistent with concerted (4 + 3) cycloadditions. In
      many instances, the (4 + 3) products were susceptible to fragmentation or
      rearrangement in the presence of the Lewis acid. 

PMID- 25984923
TI  - Treatment for postpolio syndrome.
AB  - BACKGROUND: Postpolio syndrome (PPS) may affect survivors of paralytic
      poliomyelitis and is characterised by a complex of neuromuscular symptoms leading
      to a decline in physical functioning. The effectiveness of pharmacological
      treatment and rehabilitation management in PPS is not yet established. This is an
      update of a review first published in 2011. OBJECTIVES: To systematically review
      the evidence from randomised and quasi-randomised controlled trials for the
      effect of any pharmacological or non-pharmacological treatment for PPS compared
      to placebo, usual care or no treatment.  SEARCH METHODS: We searched the
      following databases on 21 July 2014: Cochrane Neuromuscular Disease Group
      Specialized Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL Plus. We also checked reference
      lists of all relevant articles, searched the Database of Abstracts of Reviews of
      Effects (DARE), the Health Technology Assessment (HTA) Database and trial
      registers and contacted investigators known to be involved in research in this
      area. SELECTION CRITERIA: Randomised and quasi-randomised trials of any form of
      pharmacological or non-pharmacological treatment for people with PPS. The primary
      outcome was self perceived activity limitations and secondary outcomes were
      muscle strength, muscle endurance, fatigue, pain and adverse events. DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
      The Cochrane Collaboration. MAIN RESULTS: We included 10 pharmacological
      (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine,
      amantadine, prednisone) and three non-pharmacological (muscle strengthening,
      rehabilitation in a warm climate (that is temperature +/- 25 degrees C, dry and
      sunny) and a cold climate (that is temperature +/- 0 degrees C, rainy or snowy),
      static magnetic fields) studies with a total of 675 participants with PPS in this
      review. None of the included studies were completely free from any risk of bias,
      the most prevalent risk of bias being lack of blinding.There was moderate- and
      low-quality evidence that IVIg has no beneficial effect on activity limitations
      in the short term and long term, respectively, and inconsistency in the evidence
      for effectiveness on muscle strength. IVIg caused minor adverse events in a
      substantial proportion of the participants. Results of one trial provided very
      low-quality evidence that lamotrigine might be effective in reducing pain and
      fatigue, resulting in fewer activity limitations without generating adverse
      events. Data from two single trials suggested that muscle strengthening of thumb
      muscles (very low-quality evidence) and static magnetic fields (moderate-quality
      evidence) are safe and beneficial for improving muscle strength and pain,
      respectively, with unknown effects on activity limitations. Finally, there was
      evidence varying from very low quality to high quality that modafinil,
      pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold
      climate are not beneficial in PPS. AUTHORS' CONCLUSIONS: Due to insufficient good
      quality data and lack of randomised studies, it was impossible to draw definite
      conclusions about the effectiveness of interventions for PPS. Results indicated
      that IVIg, lamotrigine, muscle strengthening exercises and static magnetic fields
      may be beneficial but need further investigation to clarify whether any real and
      meaningful effect exists.

PMID- 25984924
TI  - Molecular analysis of patients with severe congenital factor X deficiency: First
      report from north and northwest of Iran.
AB  - Background Congenital FX deficiency is an extremely rare autosomal recessive
      disorder, mostly present in regions with a high rate of consanguinity, with an
      incidence of approximately 1:2,000,000 in the general population. The aim of this
      study was to evaluate the clinical manifestations and to provide a molecular
      analysis of 14 patients with homozygous factor X deficiency. Methods We evaluated
      the results of clinical and molecular characterization of 14 new cases (10 males,
      4 females aged from 4 to 17 years) of FXD (FX activity <1%) in North and
      Northwest of Iran. FXD was diagnosed by clinical findings and routine laboratory
      tests. The PCR products of all the eight exons and their intron-exon boundaries
      were sequenced using DNA sequencer. Results Mean age of patients and mean age at
      diagnosis were 9 and 2.5 years, respectively. The molecular analysis revealed
      five different mutations, all of them were previously described. Molecular
      analysis showed five different homozygous and double heterozygous mutations
      including Arg-1Thr, Cys81Tyr, Gly78Asp, IVS1+3, and IVS2-3. Discussion The study
      of a large population of factor X patients from three institutions indicated that
      FXD was one of the most serious among rare bleeding disorders and that factor X
      gene mutation may be related to bleeding tendency in patients.

PMID- 25984925
TI  - Ternary Spinel MCo2O4 (M = Mn, Fe, Ni, and Zn) Porous Nanorods as Bifunctional
      Cathode Materials for Lithium-O2 Batteries.
AB  - The development of Li-O2 battery electrocatalysts has been extensively explored
      recently. The Co3O4 oxide has attracted much attention because of its
      bifunctional activity and high abundance. In the present study, toxic Co(2+) has
      been replaced through the substitution on the tetrahedral spinel A site ions with
      environmental friendly metals (Mn(2+), Fe(2+), Ni(2+), and Zn(2+)), and porous
      nanorod structure are formed. Among these spinel MCo2O4 cathodes, the FeCo2O4
      surface has the highest Co(3+) ratio. Thus, oxygen can be easily adsorbed onto
      the active sites. In addition, Fe(2+) in the tetrahedral site can easily release
      electrons to reduce oxygen and oxidize to half electron filled Fe(3+). The
      FeCo2O4 cathode exhibits the highest discharging plateau and lowest charging
      plateau as shown by the charge-discharge profile. Moreover, the porous FeCo2O4
      nanorods can also facilitate achieving high capacity and good cycling
      performance, which are beneficial for O2 diffusion channels and Li2O2
      formation/decomposition pathways. 

PMID- 25984926
TI  - 3D printed plastics for beam modulation in proton therapy.
AB  - Two 3D printing methods, fused filament fabrication (FFF) and PolyJetTM (PJ) were
      investigated for suitability in clinical proton therapy (PT) energy modulation.
      Measurements of printing precision, printed density and mean stopping power are
      presented. FFF is found to be accurate to 0.1 mm, to contain a void fraction of
      13% due to air pockets and to have a mean stopping power dependent on geometry.
      PJ was found to print accurate to 0.05 mm, with a material density and mean
      stopping power consistent with solid poly(methyl methacrylate) (PMMA). Both FFF
      and PJ were found to print significant, sporadic defects associated with sharp
      edges on the order of 0.2 mm. Site standard PT modulator wheels were printed
      using both methods. Measured depth-dose profiles with a 74 MeV beam show poor
      agreement between PMMA and printed FFF wheels. PJ printed wheel depth-dose agreed
      with PMMA within 1% of treatment dose except for a distal falloff discrepancy of
      0.5 mm.

PMID- 25984927
TI  - Correction: Comorbidities against Quality Control of VKA Therapy in Non-Valvular
      Atrial Fibrillation: A French National Cross-Sectional Study.

PMID- 25984928
TI  - Setup error and motion during deep inspiration breath-hold breast radiotherapy
      measured with continuous portal imaging.
AB  - BACKGROUND: The position and residual motion of the chest wall of breast cancer
      patients during treatment in deep inspiration breath-hold (DIBH) were
      investigated. MATERIAL AND METHODS: The study included 58 left-sided breast
      cancer patients treated with DIBH three-dimensional (3D) conformal radiotherapy
      in 15 or 25 fractions. The DIBH levels were monitored using an external marker
      block placed on the chest, either shifted 5 cm to the right at the level of the
      xiphoid process (Group 1, 27 consecutive patients) or placed medially on the
      inferior part of the sternum (Group 2, 31 consecutive patients). At every third
      treatment fraction, continuous portal images were acquired. The time-resolved
      chest wall position during treatment was compared with the planned position to
      determine the inter-fraction setup errors and the intra-fraction motion of the
      chest wall. RESULTS: The DIBH compliance was 95% during both recruitment periods.
      A tendency of smaller inter-fraction setup errors and intra-fraction motion was
      observed for group 2 (medial marker block position). However, apart from a
      significantly reduced inter-field random shift (sigma = 1.7 mm vs. sigma = 0.9
      mm, p = 0.005), no statistically significant differences between the groups were
      found. In a combined analysis, the group mean inter-fraction setup error was M = 
      0.1 mm, with random and systematic errors of sigma = 1.7 mm and Sigma = 1.4 mm.
      The group mean inter-field shift was M = 0.0 (sigma = 1.3 mm and Sigma = 1.1 mm)
      and the group mean standard deviation of the intra-field motion was 0.5 mm. The
      absolute setup error had a maximum of 16.3 mm, exceeding 5 mm in 2.2% of the
      imaged fields. CONCLUSION: Compared to free breathing treatments, the primary
      benefit of the DIBH technique was the separation of the heart from the target
      rather than more accurate targeting. Despite a small gating window, occasional
      large errors in the chest wall position were observed for some patients,
      illustrating limitations of the external marker block as surrogate in a broad
      patient population.

PMID- 25984929
TI  - Predictors of acute toxicities during definitive chemoradiation using intensity
      modulated radiotherapy for anal squamous cell carcinoma.
AB  - PURPOSE: To identify clinical and dosimetric factors associated with acute
      hematologic and gastrointestinal (GI) toxicities during definitive therapy using
      intensity-modulated radiotherapy (IMRT) for anal squamous cell carcinoma (ASCC).
      MATERIALS AND METHODS: We retrospectively analyzed 108 ASCC patients treated with
      IMRT. Clinical information included age, gender, stage, concurrent chemotherapy,
      mitomycin (MMC) chemotherapy and weekly hematologic and GI toxicity during IMRT.
      From contours of the bony pelvis and bowel, dose-volume parameters were
      extracted. Logistic regression models were used to test associations between
      toxicities and clinical or dosimetric predictors. RESULTS: The median age was 59
      years, 81 patients were women and 84 patients received concurrent MMC and 5
      fluorouracil (5FU). On multivariate analysis (MVA), the model most predictive of
      Grade 2 + anemia included the maximum bony pelvis dose (Dmax), female gender, and
      T stage [p = 0.035, cross validation area under the curve (cvAUC) = 0.66]. The
      strongest model of Grade 2 + leukopenia included V10 (percentage of pelvic bone
      volume receiving >= 10 Gy) and number of MMC cycles (p = 0.276, cvAUC = 0.57).
      The model including MMC cycle number and T stage correlated best with Grade 2 +
      neutropenia (p = 0.306, cvAUC = 0.57). The model predictive of combined Grade 2 +
      hematologic toxicity (HT) included V10 and T stage (p = 0.016, cvAUC = 0.66). A
      model including VA45 (absolute bowel volume receiving >= 45 Gy) and MOH5 (mean
      dose to hottest 5% of bowel volume) best predicted diarrhea (p = 0.517, cvAUC =
      0.56). CONCLUSION: Dosimetric constraints to the pelvic bones should be
      integrated into IMRT planning to reduce toxicity, potentially reducing treatment
      interruptions and improving disease outcomes in ASCC. Specifically, our results
      indicate that Dmax should be confined to <= 57 Gy to minimize anemia and that V10
      should be restricted to <= 87% to reduce incidence of all HT.

PMID- 25984930
TI  - Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and
      meta-analysis of 76 studies.
AB  - BACKGROUND: In cancer cells, metabolism is shifted to aerobic glycolysis with
      lactate production coupled with a higher uptake of glucose as the main energy
      source. Lactate dehydrogenase (LDH) catalyzes the reduction of pyruvate to form
      lactate, and serum level is often raised in aggressive cancer and hematological
      malignancies. We have assessed the prognostic value of LDH in solid tumors.
      MATERIAL AND METHODS: A systematic review of electronic databases was conducted
      to identify publications exploring the association of LDH with clinical outcome
      in solid tumors. Overall survival (OS) was the primary outcome, and cancer
      specific survival (CSS), progression-free survival (PFS), and disease-free
      survival (DFS) were secondary outcomes. Data from studies reporting a hazard
      ratio (HR) and 95% confidence interval (CI) were pooled in a meta-analysis.
      Pooled HRs were computed and weighted using generic inverse-variance and random
      effect modeling. All statistical tests were two-sided. RESULTS: Seventy-six
      studies comprising 22 882 patients, mainly with advanced disease, were included
      in the analysis. Median cut-off of serum LDH was 245 U/L. Overall, higher LDH
      levels were associated with a HR for OS of 1.7 (95% CI 1.62-1.79; p < 0.00001) in
      73 studies. The prognostic effect was highest in renal cell, melanoma, gastric,
      prostate, nasopharyngeal and lung cancers (all p < 0.00001). HRs for PFS was 1.75
      (all p < 0.0001). CONCLUSIONS: A high serum LDH level is associated with a poor
      survival in solid tumors, in particular melanoma, prostate and renal cell
      carcinomas, and can be used as a useful and inexpensive prognostic biomarker in
      metastatic carcinomas.

PMID- 25984931
TI  - The impact of complete chemotherapy stop on the overall survival of patients with
      advanced colorectal cancer in first-line setting: A meta-analysis of randomized
      trials.
AB  - BACKGROUND: The impact of the duration of chemotherapy on the overall survival of
      patients with metastatic colorectal cancer (mCRC) is controversial and studies
      have failed to define a clear standard. METHODS: We searched medical literature
      databases and oncology conferences proceedings for randomized controlled trials
      (RCT) that compared the overall survival of mCRC patients who received continuous
      first-line chemotherapy until disease progression versus those who were offered
      complete treatment stop after a fixed number of cycles. Studies including
      targeted agents were also included. A meta-analysis of reported hazard ratios
      (HRs) for survival was performed. RESULTS: We retrieved 240 trials, of which six
      were eligible and five were included in the pooled analysis of overall survival
      (N = 3061). The overall survival between continuously delivered chemotherapy and
      complete stop was not statistically different (HR = 0.93, 95% CI 0.85-1.02; p =
      0.12; I2 = 5%). The results are similar when we analyzed separately the trials
      performing randomization before versus after induction therapy. The median
      chemotherapy free interval in the complete stop group was 3.9 months (3.6-4.3
      months). Chemotherapy administered until progression was associated with more
      adverse effects and impaired quality of life. CONCLUSION: Compared with first
      line continuous chemotherapy administered until disease progression, complete
      treatment stop did not have a detrimental impact on the overall survival of
      patients with mCRC. Identification of predictive biomarkers could help clinicians
      to select the patients who would benefit from continuous cancer-directed
      therapies.

PMID- 25984932
TI  - Who's in the Room? A Parent-Focused Family Therapy for Adolescent Anorexia
      Nervosa.
AB  - Family therapy is often assumed to involve the whole family; that is both parents
      and children attending the therapist's office together. In practice, however,
      which family members are included in family therapy, how often, and in what ways,
      is much more variable. In this article we provide an overview of the recent
      history of family therapy in regard to who is directly involved in therapy, and
      contrast changing practices in the eating disorders field with those in the
      family therapy field more widely. This overview leads into a discussion of
      current practices in family-based treatment for adolescent anorexia nervosa and
      the development of a new form of family therapy that is parent-focused. 

PMID- 25984934
TI  - MEMS sensors for assessing flow-related control of an underwater biomimetic
      robotic stingray.
AB  - A major difference between manmade underwater robotic vehicles (URVs) and
      undersea animals is the dense arrays of sensors on the body of the latter which
      enable them to execute extreme control of their limbs and demonstrate super
      maneuverability. There is a high demand for miniaturized, low-powered,
      lightweight and robust sensors that can perform sensing on URVs to improve their
      control and maneuverability. In this paper, we present the design, fabrication
      and experimental testing of two types of microelectromechanical systems (MEMS)
      sensors that benefit the situational awareness and control of a robotic stingray.
      The first one is a piezoresistive liquid crystal polymer haircell flow sensor
      which is employed to determine the velocity of propagation of the stingray. The
      second one is Pb(Zr(0.52)Ti(0.48))O3 piezoelectric micro-diaphragm pressure
      sensor which measures various flapping parameters of the stingray's fins that are
      key parameters to control the robot locomotion. The polymer flow sensors
      determine that by increasing the flapping frequency of the fins from 0.5 to 3 Hz
      the average velocity of the stingray increases from 0.05 to 0.4 BL s(-1),
      respectively. The role of these sensors in detecting errors in control and
      functioning of the actuators in performing tasks like flapping at a desired
      amplitude and frequency, swimming at a desired velocity and direction are
      quantified. The proposed sensors are also used to provide inputs for a model
      predictive control which allows the robot to track a desired trajectory. Although
      a robotic stingray is used as a platform to emphasize the role of the MEMS
      sensors, the applications can be extended to most URVs.

PMID- 25984933
TI  - Synthesis of (11)C-Labeled Thiamine and Fursultiamine for in Vivo Molecular
      Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography.
AB  - To enable in vivo analysis of the kinetics of vitamin B1 (thiamine) and its
      derivatives by positron emission tomography (PET), (11)C-labeled thiamine
      ([(11)C]-1) has been synthesized. This was carried out via a rapid, multistep
      synthesis consisting of Pd(0)-mediated C-[(11)C]methylation of a thiazole ring
      for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [(11)C]-1
      was also converted to (11)C-labeled fursultiamine ([(11)C]-2), a prodrug of
      vitamin B1, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid
      sodium salt. Characterization of [(11)C]-1 and [(11)C]-2 showed them to be
      suitable for use as PET probes for in vivo pharmacokinetic and medical studies.
      The total durations of the preparations of [(11)C]-1 and [(11)C]-2 were shorter
      than 60 and 70 min, respectively. The [(11)C]CH3I-based decay-corrected
      radiochemical yields of [(11)C]-1 and [(11)C]-2 were 9-16% and 4-10%,
      respectively. The radioactivities of the final injectable solutions of [(11)C]-1
      and [(11)C]-2 were 400-700 and 100-250 MBq, respectively. The radiochemical
      purity of both [(11)C]-1 and [(11)C]-2 was 99%, and the chemical purities of
      [(11)C]-1 and [(11)C]-2 were 99% and 97-99%, respectively. In vivo PET imaging of
      normal rats was illustrated by the distribution of [(11)C]-1 and [(11)C]-2
      following intravenous injection. 

PMID- 25984936
TI  - Visual choice behavior by bumblebees (Bombus impatiens) confirms unsupervised
      neural network's predictions.
AB  - The behavioral experiment herein tests the computational load hypothesis
      generated by an unsupervised neural network to examine bumblebee (Bombus
      impatiens) behavior at 2 visual properties: spatial frequency and symmetry.
      Untrained "flower-naive" bumblebees were hypothesized to prefer symmetry only
      when the spatial frequency of artificial flowers is high and therefore places
      great information-processing demands on the bumblebees' visual system. Bumblebee
      choice behavior was recorded using high-definition motion-sensitive camcorders.
      The results support the computational model's prediction: 1-axis symmetry
      influenced bumblebees' preference behavior at low and high spatial frequency
      patterns. Additionally, increasing the level of symmetry from 1 axis to 4 axes
      amplified preference toward the symmetric patterns of both low and high spatial
      frequency patterns. The results are discussed in the context of the artificial
      neural network model and other hypotheses generated from the behavioral
      literature.

PMID- 25984935
TI  - Modulation of Axial-Ligand Binding and Releasing Processes onto the Triazole
      Bearing Nickel(II) Picket-Fence Porphyrins: Steric Repulsion versus Hydrogen
      Bonding Effects.
AB  - N-(p-Methoxycarbonylbenzyl) triazole (BTz) substituents have been introduced to
      Ni(II) porphyrins (NiPs), in which their modulated axial-coordination processes
      have been investigated. For this study, the two types of ligands, neutral
      pyridine versus anionic cyanide, were employed to investigate an effect of BTz
      substituents. The unique microenvironments given by the BTz substituents provided
      two different effects on the axial-coordination processes of NiPs on the ground
      and excited states: (1) steric shielding and (2) donation of hydrogen-bonding
      sites. The steric shielding diminished the binding affinity of pyridine, while
      the cooperation of hydrogen bonds extraordinarily strengthened the binding
      affinity of CN(-). Interestingly, it was observed that the binding of CN(-) with
      the supporting of BTz substituents accompanied nonplanar distortion of NiPs. Such
      conformational change perturbed the electronic structure of NiPs, which gave rise
      to the modulation of coordination processes of NiPs in the excited state. As a
      consequence, photoinudced ligand binding and releasing processes of four- and six
      coordinated NiPs were changed into the dominant photoinduced ligand releasing
      process. 

PMID- 25984937
TI  - The string-pulling paradigm in comparative psychology.
AB  - String pulling is one of the most widely used paradigms in comparative
      psychology. First documented 2 millennia ago, it has been a well-established
      scientific paradigm for a century. More than 160 bird and mammal species have
      been tested in over 200 studies with countless methodological variations. The
      paradigm can be used to address a wide variety of issues on animal cognition; for
      example, what animals understand about contact and connection as well as whether
      they rely on perceptual feedback, grasp the functionality of strings, generalize
      across conditions, apply their knowledge flexibly, and possess insight. Mammals
      are typically tested on a horizontal configuration, birds on a vertical one,
      making the studies difficult to compare; in particular, pulling a string
      vertically requires better coordination and attention. A species' performance on
      the paradigm is often influenced by its ecology, especially concerning whether
      limbs are used for foraging. Many other factors can be of importance and should
      be considered. The string-pulling paradigm is easy to administer, vary, and apply
      to investigate a wide array of cognitive abilities. Although it can be and has
      been used to compare species, divergent methods and unclear reporting have
      limited its comparative utility. With increasing research standards, the paradigm
      is expected to become an even more fundamental tool in comparative psychology.

PMID- 25984938
TI  - Working memory and reference memory tests of spatial navigation in mice (Mus
      musculus).
AB  - Researchers in spatial cognition have debated for decades the specificity of the
      mechanisms through which spatial information is processed and stored.
      Interestingly, although rodents are the preferred animal model for studying
      spatial navigation, the behavioral methods traditionally used to assess spatial
      memory do not effectively test the predictions of specificity in their
      representation. To address such issues, the present study tested the ability of
      mice to use boundary geometry and features to remember a goal location across 2
      types of tasks--a working memory task with a changing goal location, and a
      reference memory task with 1 rewarded goal location. We show for the first time
      that mice, like other animals, can successfully encode boundary geometry in a
      working memory spatial mapping task, just as they do in a reference memory task.
      Their use of a nongeometric featural cue (striped pattern), in contrast, was more
      limited in the working memory task, although it quickly improved in the reference
      memory task. We discuss the implications of these findings for future research on
      the neural and genetic underpinnings of spatial representations.

PMID- 25984939
TI  - Reply to Jaakkola (2014): "Do animals understand invisible displacement? A
      critical review".
AB  - Jaakkola (2014) critiques studies that investigate nonhuman capacities to track
      objects undergoing invisible displacements. She states that the results of most
      of these studies are tainted by cuing, that conceptual understanding is lacking,
      and that, as a consequence, great apes are the only nonhumans to have full Stage
      6 object permanence. Any critique, however, must clearly take into account all
      published information on the techniques being used, including more recent data
      that counter its negative claims. Furthermore, disagreements as to the
      interpretation of the underlying mechanisms, although common, need not always
      cast doubt on the actual findings reported. Here I present material with respect
      to Grey parrots (Psittacus erithacus) to counter Jaakkola's critique. First, I
      take issue with Jaakkola's claims of cuing, based both on data from newer studies
      and citations from the original material. Second, I discuss her suggestions that
      associative learning rather than inferential mechanisms underlie demonstrated
      performance, pointing out some difficulties in drawing clear lines between the 2
      interpretations. In sum, I argue that Grey parrots, at least, do indeed succeed
      on tasks involving invisible displacement, and demonstrate full object
      permanence.

PMID- 25984940
TI  - Making the strongest argument: Reply to Pepperberg (2015).
AB  - Jaakkola (2014) argued that because the majority of studies of animals'
      understanding of invisible displacement did not adequately control for the use of
      alternative lower-level strategies, clear and solid evidence for a conceptual
      understanding of invisible displacement existed only for great apes. Pepperberg
      (2015) takes issue with this conclusion with respect to Grey parrots. While I
      agree that olfactory and social cueing may not be issues of concern for parrots,
      I reiterate the need for a study that adequately controls for associative
      learning before we can confidently claim that parrots understand invisible
      displacement.

PMID- 25984941
TI  - THE HUMAN BEHAVIOR RATING SCALE-BRIEF: A TOOL TO MEASURE 21ST CENTURY SKILLS OF K
      12 LEARNERS.
AB  - Currently there is a call for brief concise measurements to appraise relevant
      21st century college readiness skills in K-12 learners. This study employed K-12
      teachers' ratings for over 3,000 students for an existing 91-item rating scale,
      the Human Behavior Rating Scale, that measured the 21st century skills of
      persistence, curiosity, externalizing affect, internalizing affect, and
      cognition. Teachers' ratings for K-12 learners were used to develop a brief,
      concise, and manageable 30-item tool, the Human Behavior Rating Scale-Brief.
      Results yielded high internal consistency coefficients and inter-item
      correlations. The items were not biased with regard to student sex or race, and
      were supported through confirmatory factor analyses. In addition, when teachers'
      ratings were compared with students' academic and behavioral performance data,
      moderate to strong relationships were revealed. This study provided an essential
      first step in the development of a psychometrically sound, manageable, and brief
      tool to appraise 21st century skills in K-12 learners.

PMID- 25984942
TI  - ETHICAL LEADERSHIP AND EMPLOYEE VOICE: EMPLOYEE SELF-EFFICACY AND SELF-IMPACT AS
      MEDIATORS.
AB  - Previous studies have used social learning theory to explain the influence of
      ethical leadership. This study continues the previous research by using social
      learning theory to explain the mediating effect of self-efficacy on the
      relationship between ethical leadership and employee voice. In addition, this
      study extends previous studies by introducing expectancy theory to explore
      whether self-impact also mediates the relationship between ethical leadership and
      employee voice. Ethical leadership, self-efficacy, self-impact, and employee
      voice were assessed using paired surveys among 59 supervisors and 295
      subordinates employed at nine firms in the People's Republic of China. Using HLM
      and SEM analyses, the results revealed that ethical leadership was positively
      related to employee voice and that this relationship was partially mediated by
      both self-efficacy and self-impact.

PMID- 25984944
TI  - First Direct Observation of Stable Internally Ordered Janus Nanoparticles Created
      by Lipid Self-Assembly.
AB  - We present the first observation of Janus nanoparticles consisting of stable,
      coexisting ordered mesophases in discrete particles created by lipid self
      assembly. Cryo-TEM images provided visual identification of the multicompartment
      Janus nanoparticles and, combined with SAXS data, confirmed the presence of mixed
      cubic phases and mixed cubic/hexagonal phases within individual nanoparticles. We
      further investigated computer visualization models to interpret the potential
      interface between the interconnected coexisting nanostructured domains within a
      single nanoparticle. 

PMID- 25984943
TI  - Ratios of Four STAT3 Splice Variants in Human Eosinophils and Diffuse Large B
      Cell Lymphoma Cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a key mediator of
      leukocyte differentiation and proliferation. The 3' end of STAT3 transcripts is
      subject to two alternative splicing events. One results in either full-length
      STAT3alpha or in STAT3beta, which lacks part of the C-terminal transactivation
      domain. The other is at a tandem donor (5') splice site and results in the codon
      for Ser-701 being included (S) or excluded (DeltaS). Despite the proximity of Ser
      701 to the site of activating phosphorylation at Tyr-705, DeltaS/S splicing has
      barely been studied. Sequencing of cDNA from purified eosinophils revealed the
      presence of four transcripts (S-alpha, DeltaS-alpha, S-beta, and DeltaS-beta)
      rather than the three reported in publically available databases from which
      DeltaS-beta is missing. To gain insight into regulation of the two alternative
      splicing events, we developed a quantitative(q) PCR protocol to compare
      transcript ratios in eosinophils in which STAT3 is upregulated by cytokines,
      activated B cell diffuse large B cell Lymphoma (DLBCL) cells in which STAT3 is
      dysregulated, and in germinal center B cell-like DLBCL cells in which it is not.
      With the exception of one line of activated B cell DLCBL cells, the four variants
      were found in roughly the same ratios despite differences in total levels of
      STAT3 transcripts. S-alpha was the most abundant, followed by S-beta. DeltaS
      alpha and DeltaS-beta together comprised 15.6 +/- 4.0 % (mean +/- SD, n = 21) of
      the total. The percentage of STAT3beta variants that were DeltaS was 1.5-fold
      greater than of STAT3alpha variants that were DeltaS. Inspection of Illumina's
      "BodyMap" RNA-Seq database revealed that the DeltaS variant accounts for 10-26 %
      of STAT3 transcripts across 16 human tissues, with less variation than three
      other genes with the identical tandem donor splice site sequence. Thus, it seems
      likely that all cells contain the S-alpha, DeltaS-alpha, S-beta, and DeltaS-beta
      variants of STAT3.

PMID- 25984945
TI  - Could CCI or FBCI Fully Eliminate the Impact of Curve Flexibility When Evaluating
      the Surgery Outcome for Thoracic Curve Idiopathic Scoliosis Patient? A
      Retrospective Study.
AB  - PURPOSE: To clarify if CCI or FBCI could fully eliminate the influence of curve
      flexibility on the coronal correction rate. METHODS: We reviewed medical record
      of all thoracic curve AIS cases undergoing posterior spinal fusion with all
      pedicle screw systems from June 2011 to July 2013. Radiographical data was
      collected and calculated. Student t test, Pearson correlation analysis and linear
      regression analysis were used to analyze the data. RESULTS: 60 were included in
      this study. The mean age was 14.7 y (10-18 y) with 10 males (17%) and 50 females
      (83%). The average Risser sign was 2.7. The mean thoracic Cobb angle before
      operation was 51.9 degrees . The mean bending Cobb angle was 27.6 degrees  and
      the mean fulcrum bending Cobb angle was 17.4 degrees . The mean Cobb angle at 2
      week after surgery was 16.3 degrees . The Pearson correlation coefficient r
      between CCI and BFR was -0.856(P<0.001), and between FBCI and FFR was -0.728
      (P<0.001). A modified FBCI (M-FBCI) = (CR-0.513)/BFR or a modified CCI (M-CCI) =
      (CR-0.279)/FFR was generated by curve estimation has no significant correlation
      with FFR (r=-0.08, p=0.950) or with BFR (r=0.123, p=0.349). CONCLUSIONS: Fulcrum
      bending radiographs may better predict the outcome of AIS coronal correction than
      bending radiographs in thoracic curveAIS patients. Neither CCI nor FBCI can fully
      eliminate the impact of curve flexibility on the outcome of correction. A
      modified CCI or FBCI can better evaluating the corrective effects of different
      surgical techniques or instruments.

PMID- 25984946
TI  - Quantifying the consistency of scientific databases.
AB  - Science is a social process with far-reaching impact on our modern society. In
      recent years, for the first time we are able to scientifically study the science
      itself. This is enabled by massive amounts of data on scientific publications
      that is increasingly becoming available. The data is contained in several
      databases such as Web of Science or PubMed, maintained by various public and
      private entities. Unfortunately, these databases are not always consistent, which
      considerably hinders this study. Relying on the powerful framework of complex
      networks, we conduct a systematic analysis of the consistency among six major
      scientific databases. We found that identifying a single "best" database is far
      from easy. Nevertheless, our results indicate appreciable differences in mutual
      consistency of different databases, which we interpret as recipes for future
      bibliometric studies. 

PMID- 25984947
TI  - Suicide Trends Among Elementary School-Aged Children in the United States From
      1993 to 2012.
AB  - IMPORTANCE: Suicide is a leading cause of death among school-aged children
      younger than 12 years but little is known about the epidemiology of suicide in
      this age group. OBJECTIVE: To describe trends in suicide among US children
      younger than 12 years by sociodemographic group and method of death. DESIGN,
      SETTING, AND PARTICIPANTS: Period trend analysis of national mortality data on
      suicide in children aged 5 to 11 years in the United States from January 1, 1993,
      to December 31, 2012. Data were analyzed per 5-year periods, between 1993 to 1997
      and 2008 to 2012. MAIN OUTCOMES AND MEASURES: Number of suicide deaths and crude
      suicide rates. Period trends in rates of suicide were estimated using negative
      binomial regression incidence rate ratios (IRRs). RESULTS: The overall suicide
      rate among children aged 5 to 11 years remained stable between 1993 to 1997 and
      2008 to 2012 (from 1.18 to 1.09 per 1 million; IRR = 0.96; 95% CI, 0.90-1.03).
      However, the suicide rate increased significantly in black children (from 1.36 to
      2.54 per 1 million; IRR = 1.27; 95% CI, 1.11-1.45) and decreased in white
      children (from 1.14 to 0.77 per 1 million; IRR = 0.86; 95% CI, 0.79-0.94). The
      overall firearm suicide rate (IRR = 0.69; 95% CI, 0.57-0.85) and firearm suicide
      rate among white boys (IRR = 0.72; 95% CI, 0.59-0.88) decreased significantly
      during the study. The rate of suicide by hanging/suffocation increased
      significantly in black boys (IRR = 1.35; 95% CI, 1.14-1.61), although the overall
      change in suicide rates by hanging/suffocation or other suicide methods did not
      change during the study. CONCLUSIONS AND RELEVANCE: The stable overall suicide
      rate in school-aged children in the United States during 20 years of study
      obscured a significant increase in suicide incidence in black children and a
      significant decrease in suicide incidence among white children. Findings
      highlight a potential racial disparity that warrants attention. Further studies
      are needed to monitor these emerging trends and identify risk, protective, and
      precipitating factors relevant to suicide prevention efforts in children younger
      than 12 years.

PMID- 25984948
TI  - Fortnightly atmospheric tides forced by spring and neap tides in coastal waters.
AB  - The influence of sea surface temperature (SST) on atmospheric processes over the
      open ocean has been well documented. However, atmospheric responses to SST in
      coastal waters are poorly understood. Oceanic stratification (and consequently,
      SST) in coastal waters largely depends on the fortnightly spring-neap tidal
      cycle, because of variations in vertical tidal mixing. Here we investigate how
      changes in SST during the fortnightly tidal cycle affect the lower-level
      atmosphere over the Seto Inland Sea, Japan. We use a combination of in situ
      measurements, satellite observations and a regional atmospheric model. We find
      that the SST in summer shows cool (warm) anomalies over most of the inland sea
      during spring (neap) tides. Additionally, surface air temperature is positively
      correlated with the SST as it varies during the fortnightly tidal cycle.
      Moreover, the fortnightly spring-neap cycle also influences the surface wind
      speed because the atmospheric boundary layer becomes stabilized or destabilized
      in response to the difference between air temperature and SST. 

PMID- 25984949
TI  - An early diagnostic tool for diabetic peripheral neuropathy in rats.
AB  - The skin's rewarming rate of diabetic patients is used as a diagnostic tool for
      early diagnosis of diabetic neuropathy. At present, the relationship between
      microvascular changes in the skin and diabetic neuropathy is unclear in
      streptozotocin (STZ) diabetic rats. The aim of this study was to investigate
      whether the skin rewarming rate in diabetic rats is related to microvascular
      changes and whether this is accompanied by changes observed in classical
      diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared
      thermography was used to assess the rewarming rate after cold exposure on the
      plantar skin of STZ diabetic rats' hind paws. Peripheral neuropathy was
      determined by the density of intra-epidermal nerve fibers (IENFs), mechanical
      sensitivity, and electrophysiological recordings. Data were obtained in diabetic
      rats at four, six, and eight weeks after the induction of diabetes and in
      controls. Four weeks after the induction of diabetes, a delayed rewarming rate,
      decreased skin blood flow and decreased density of IENFs were observed. However,
      the mechanical hyposensitivity and decreased motor nerve conduction velocity
      (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows
      that the skin rewarming rate is related to microvascular changes in diabetic
      rats. Moreover, the skin rewarming rate is a non-invasive method that provides
      more information for an earlier diagnosis of peripheral neuropathy than the
      classical monofilament test and MNCV in STZ induced diabetic rats. 

PMID- 25984950
TI  - Piperlongumine and immune cytokine TRAIL synergize to promote tumor death.
AB  - Malignant transformation results in increased levels of reactive oxygen species
      (ROS). Adaption to this toxic stress allows cancer cells to proliferate.
      Recently, piperlongumine (PL), a natural alkaloid, was identified to exhibit
      novel anticancer effects by targeting ROS signaling. PL induces apoptosis
      specifically in cancer cells by downregulating several anti-apoptotic proteins.
      Notably, the same anti-apoptotic proteins were previously found to reduce tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in
      cancer cells. Therefore, we reasoned that PL would synergize with TRAIL to
      stimulate potent apoptosis in cancer cells. We demonstrate for the first time
      that PL and TRAIL exhibit a synergistic anti-cancer effect in cancer cell lines
      of various origins. PL resulted in the upregulation of TRAIL receptor DR5, which
      potentiated TRAIL-induced apoptosis in cancer cells. Furthermore, such
      upregulation was found to be dependent on ROS and the activation of JNK and p38
      kinases. Treatment with combined PL and TRAIL demonstrated significant anti
      proliferative effects in a triple-negative breast cancer MDA-MB-231 xenograft
      model. This work provides a novel therapeutic approach for inducing cancer cell
      death. Combination of PL and TRAIL may suggest a novel paradigm for treatment of
      primary and metastatic tumors. 

PMID- 25984951
TI  - Rhodium-catalyzed endo-selective epoxide-opening cascades: formal synthesis of (
      )-brevisin.
AB  - [Rh(CO)2Cl]2 is as an effective catalyst for endo-selective cyclizations and
      cascades of epoxy-(E)-enoate alcohols, thus enabling the synthesis of oxepanes
      and oxepane-containing polyethers from di- and trisubstituted epoxides. Syntheses
      of the ABC and EF ring systems of (-)-brevisin via all endo-diepoxide-opening
      cascades using this method constitute a formal total synthesis and demonstrate
      the utility of this methodology in the context of the synthesis of marine ladder
      polyether natural products. 

PMID- 25984953
TI  - Note from the incoming editor.

PMID- 25984952
TI  - Microbiome profiles in periodontitis in relation to host and disease
      characteristics.
AB  - Periodontitis is an inflammatory condition that affects the supporting tissues
      surrounding teeth. The occurrence of periodontitis is associated with shifts in
      the structure of the communities that inhabit the gingival sulcus. Although great
      inter-subject variability in the subgingival microbiome has been observed in
      subjects with periodontitis, it is unclear whether distinct community types exist
      and if differences in microbial signatures correlate with host characteristics or
      with the variable clinical presentations of periodontitis. Therefore, in this
      study we explored the existence of different community types in periodontitis and
      their relationship with host demographic, medical and disease-related clinical
      characteristics. Clustering analyses of microbial abundance profiles suggested
      two types of communities (A and B) existed in the 34 subjects with periodontitis
      evaluated. Type B communities harbored greater proportions of certain
      periodontitis-associated taxa, including species historically associated with the
      disease, such as Porphyromonas gingivalis, Tannerella forsythia and Treponema
      denticola, and taxa recently linked to periodontitis. In contrast, subjects with
      type A communities had increased proportions of different periodontitis
      associated species, and were also enriched for health-associated species and core
      taxa (those equally prevalent in health and periodontitis). Periodontitis
      subgingival clusters were not associated with demographic, medical or disease
      specific clinical parameters other than periodontitis extent (proportion of sites
      affected), which positively correlated with the total proportion of cluster B
      signature taxa. In conclusion, two types of microbial communities were detected
      in subjects with periodontitis. Host demographics and underlying medical
      conditions did not correlate with these profiles, which instead appeared to be
      related to periodontitis extent, with type B communities present in more
      widespread disease cases. The two identified periodontitis profiles may represent
      distinct dysbiotic processes potentially requiring community-tailored therapeutic
      interventions. 

PMID- 25984954
TI  - Lifetime use of cigarettes, alcohol, marijuana and inhalants in Latino early
      adolescents.
AB  - A growing population in the US is Latinos, an ethnic group defined by people of
      origin from Latin America. By 2050, Hispanics will be at least one quarter of the
      United States population (U.S. Census Bureau, 2006 ) with a substantial
      proportion under the age of 25 (Vaughan, Kratz, & D'argent, 2011 ). Yet, the
      literature on substance use among Latino adolescents is not advancing parallel to
      the growth of the population (Szapocznik, Lopez, Prado, Schwartz, & Pantin, 2006
      ). Health concerns during early adolescence can have a lasting impact on the
      Latino community and society at large, as early substance initiation can lead to
      addiction during adulthood (Behrendt, Wittchen, Hofler, Lieb, & Beesdo, 2009 ).
      Therefore, research that aims to identify psychosocial determinants that serve as
      risk and protective factors specific to Latino early adolescents is needed as a
      critical first step in the development of culturally specific prevention
      initiatives (Vaughan et al., 2011 ). 

PMID- 25984955
TI  - Drinking Motives and Alcohol Use Behaviors among African American College
      Students: The Mediating Role of Protective Behavioral Strategies.
AB  - Drinking motives are robust predictors of alcohol use behaviors among college
      students. However, less is known about the link between drinking motives and
      alcohol use behaviors among African American college students. This study
      explored the associations between drinking motives and alcohol use behaviors in a
      sample of 215 African American college students. The study also assessed whether
      protective behavioral strategies mediated the associations between drinking
      motives and alcohol use behaviors. A direct relationship emerged between
      enhancement motives and alcohol consumption, harmful drinking and alcohol-related
      negative consequences. Protective behavioral strategies mediated each of these
      relationships. Clinical and research implications are discussed. 

PMID- 25984956
TI  - Social-Contextual Factors Associated with Alcohol Use among Adolescents of
      Traditional Alcohol User and Nonuser Ethnic Groups of Nepal.
AB  - Nepalese society has diverse ethnic groups that can be categorized based on views
      toward alcohol. In this study, adolescents from the traditional alcohol nonuser
      (TANU) and traditional alcohol user (TAU) ethnic groups of Nepal are examined for
      their: (1) alcohol use behavior and (2) social-contextual factors associated with
      alcohol use. Based on a self-administered questionnaire of adolescents, alcohol
      use was reported by 19.4% of TANU (N=544) and 40.1% TAU (N=309). Significant
      variables in a multivariate analysis of ever using alcohol were parental alcohol
      use, peer alcohol use, perceived parental approval, and perceived peer approval. 

PMID- 25984957
TI  - Predicting High School Minority Adolescents' Drinking from Their Exposure to
      White Schoolmates: Differences and Similarities among Hispanic, Black, and Asian
      U.S. Adolescents.
AB  - White students' drinking may constitute a risk factor for drinking among same
      school minority adolescents. Our study examined data from 14,986 ethnic minority
      American high school students (56% female, mean age = 15.6). Models examined
      associations between school-level White student drinking and same-school Black,
      Hispanic, and Asian adolescents' drinking, as well as whether schools'
      proportions of White students and friendships with White schoolmates moderated
      these associations. Both school-level White students' drinking and minority
      students' friendships with White schoolmates were associated with levels of
      minority student drinking. But these associations were dependent upon levels of
      other study variables. In particular, there were higher associations between
      school-level risk factors and minorities' drinking when minority adolescents had
      high proportions of Whites among their friends. 

PMID- 25984958
TI  - "We want a living solution": views of harm reduction programs in black US
      Communities.
AB  - Illicit drug use in the US remains concerning, with injection drug use linked to
      transmission of blood-borne diseases as HIV/AIDS; persons of color, including
      Black Americans, experience disproportionately higher transmission rates. Harm
      reduction programs such as methadone and needle- and syringe-exchange (NEP/SEP)
      are empirically demonstrated to reduce HIV transmission, yet are believed largely
      opposed by Black communities. Using interview data from 21 service providers of
      substance abuse and related service organizations located in and/or serving
      predominantly populations of color, this study explored perceptions of harm
      reduction programming for illicit drugs and race in the US. Criticizing each
      program for unique reasons, respondents deemed them largely inadequate and
      inappropriate responses to community drug problems. While some believed these
      programs worsen Black communities, others believed they are becoming more
      accepted there. Views were informed by racial dynamics surrounding drugs in
      society, burdens borne by program host communities, and racialized stereotypes of
      drug use. 

PMID- 25984960
TI  - Photoreduction of Sm(3+) in Nanocrystalline BaFCl.
AB  - We demonstrate that exposure of nanocrystalline BaFCl:Sm(3+) X-ray storage
      phosphor to blue laser pulses with peak power densities on the order of 10
      GW/cm(2) results in conversion of Sm(3+) to Sm(2+). This photoreduction is found
      to be strongly power-dependent with an initial fast rate, followed by a slower
      rate. The photoreduction appears to be orders of magnitude more efficient than
      that for previously reported systems, and it is estimated that up to 50% of the
      samarium ions can be photoreduced to the divalent state. The main mechanism is
      most likely based on multiphoton electron-hole creation, followed by subsequent
      trapping of the electrons in the conduction band at the Sm(3+) centers.
      Nanocrystalline BaFCl:Sm(3+) is an efficient photoluminescent X-ray storage
      phosphor with possible applications as dosimetry probes, and the present study
      shows for the first time that the power levels of the blue light have to be kept
      relatively low to avoid the generation of Sm(2+) in the readout process. A system
      comprising the BaFCl:Sm(3+) nanocrystallites embedded into a glass is also
      envisioned for 3D memory applications. 

PMID- 25984959
TI  - Assessing treatment fidelity in a cultural adaptation of motivational
      interviewing.
AB  - The efficacy of motivational interviewing (MI) for addictions is well documented.
      Grounding MI in social/cultural priorities may enhance treatment response. We
      evaluate the method of assessing competence using the motivational interviewing
      treatment integrity system (MITI) for standard MI and culturally adapted MI
      (CAMI) delivered to Latino heavy drinkers. Twenty audiotapes (MI, n = 10; CAMI, n
      = 10) were MITI coded by two raters unaware of treatment assignment. Inter-rater
      reliabilities were excellent (.78-.99) except for CAMI complex reflections,
      global ratings of empathy, and MI spirit. The MITI reliably evaluates MI and CAMI
      treatment fidelity. Future research should investigate lower reliabilities for MI
      global and complex reflections cross-culturally. 

PMID- 25984961
TI  - An optical setup for electric field measurements in MRI with high spatial
      resolution.
AB  - Electric field measurements in the magnetic resonance (MR) imaging environment
      are important to assess potentially dangerous radio-frequency (RF) heating in the
      vicinity of metallic structures such as coils, implants or catheters. So far, E
      field measurements have been performed with dipole antennas that lag of limited
      spatial resolution and which are difficult to use in the magnet bore as they
      interfere with the RF transmit field of the MRI system. In this work an electro
      optic sensor is presented that utilizes the Pockels effect to measure the E-field
      in a clinical MR system with high spatial resolution. This sensor consists of
      dielectric materials only and thus, it only minimally influences the measured E
      field distribution. A 10 m long flexible optical fiber connects the small sensor
      head to a remote processing unit where the optical signal is transformed into an
      electrical output signal. Spatially resolved qualitative E-field measurements
      were performed in a 1.5 T clinical MR system in the vicinity of metallic samples
      and an active tracking catheter with a resolution of up to 1 mm. The near-field
      pattern of a resonant U-shaped metallic sample was clearly identified and
      compared with numerical simulations. A more complex field behavior was found for
      the tracking catheter where strong E-field enhancements were observed at the
      distal tip and at its proximal part outside the phantom solution. Due to its sub
      mm spatial resolution the optical sensor approach provides detailed insight into
      the complex and difficult to access field distributions close to implants and
      metallic structures and has turned out to be promising tool for MRI field and
      safety inspections.

PMID- 25984962
TI  - Analysis of nifedipine in human plasma and amniotic fluid by liquid
      chromatography-tandem mass spectrometry and its application to clinical
      pharmacokinetics in hypertensive pregnant women.
AB  - Nifedipine is a dihydropyridine calcium channel blocker used for the treatment of
      hypertension in pregnant women. A liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method was developed and validated for analysis of nifedipine in human
      plasma and amniotic fluid. Separation of nifedipine and nitrendipine (IS) was
      performed using a LiChroCART((r)) RP-Select B column and a mixture of
      water:acetonitrile:glacial acetic acid (30:70:0.5 v/v) as the mobile phase.
      Aliquots of 500MUL of biological samples were extracted at pH 13 using
      dichloromethane:n-pentane (3:7 v/v). The validated method was applied to a study
      of the pharmacokinetics of nifedipine in human plasma and amniotic fluid samples
      collected up to 12h after administration of the last slow-release nifedipine
      (20mg/12h) dose to 12 hypertensive pregnant women. The estimated pharmacokinetic
      parameters of nifedipine showed a mean AUC(0-12) of 250.2ngh/mL, ClT/F of
      89.2L/h, Vd/F of 600.0L and t1/2 5.1h. The mean amniotic fluid/plasma
      concentration ratio was 0.05. The methods proved to be highly sensitive by
      showing a lower quantification limit of 0.1ng/mL for both matrices. And this
      study reports for the first time the complete development and validation of the
      method to quantify nifedipine in amniotic fluid using LC-MS-MS. 

PMID- 25984963
TI  - Analysis of drugs in plasma samples from schizophrenic patients by column
      switching liquid chromatography-tandem mass spectrometry with organic-inorganic
      hybrid cyanopropyl monolithic column.
AB  - This study reports on the development of a rapid, selective, and sensitive column
      switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to
      analyze sixteen drugs (antidepressants, anticonvulsants, anxiolytics, and
      antipsychotics) in plasma samples from schizophrenic patients. The developed
      organic-inorganic hybrid monolithic column with cyanopropyl groups was used for
      the first dimension of the column-switching arrangement. This arrangement enabled
      online pre-concentration of the drugs (monolithic column) and their subsequent
      analytical separation on an XSelect SCH C18 column. The drugs were detected on a
      triple quadrupole tandem mass spectrometer (multiple reactions monitoring mode)
      with an electrospray ionization source in the positive ion mode. The developed
      method afforded adequate linearity for the sixteen target drugs; the coefficients
      of determination (R(2)) lay above 0.9932, the interassay precision had
      coefficients of variation lower than 6.5%, and the relative standard error values
      of the accuracy ranged from -14.0 to 11.8%. The lower limits of quantification in
      plasma samples ranged from 63 to 1250pgmL(-1). The developed method successfully
      analyzed the target drugs in plasma samples from schizophrenic patients for
      therapeutic drug monitoring (TDM). 

PMID- 25984964
TI  - Pharmacokinetic of 5 components after oral administration of Fructus Forsythiae
      by HPLC-MS/MS and the effects of harvest time and administration times.
AB  - The unripe Fructus Forsythiae (Qingqiao) and ripe Fructus Forsythiae (Laoqiao)
      are two types of the clinical forms of commercial fructus of Forsythia
      suspensa(Thunb.) Vahl. There is limited information available for differences in
      pharmacokinetic properties of active components between unripe and ripe Fructus
      Forsythiae in vivo. A rapid and sensitive liquid chromatography-tandem mass
      spectrometric (LC-MS/MS) method was developed and validated for the simultaneous
      determination of 9 typical components in rat plasma. The separation of nine
      analytes was performed on an Eclipse plus C18 (4.6mm*100mm, 1.8MUm) column with
      the mobile phases consisted of a mixture of 0.1% formic acid in water and
      acetonitrile. Method validation indicated that the developed method was rapid,
      specific and sensitive. It was found that the AUC(0-24h) of 5 ingredients
      (forsythoside A, rutin, phillyrin, isorhamnetin and quercetin) in rats after
      single orally administrated unripe Fructus Forsythiae also had significant
      differences compared with those after single dose oral administration of ripe
      Fructus Forsythiae extract. The systemic exposure of 5 ingredients after multiple
      oral administration of Fructus Forsythiae extract had significantly increased
      than those after single oral administration. The results indicated that harvest
      time is not only effects the contents but the bioavailability of active
      components of Fructus Forsythiae, which suggests that the rate and extent of drug
      metabolism were altered when the clinical forms of commercial Fructus Forsythiae
      with different harvest time. The administration times could influence the
      bioavailability of active components of Fructus Forsythiae. 

PMID- 25984965
TI  - A pre-clinical pharmacokinetic study in rats of three naturally occurring iridoid
      glycosides, Picroside-I, II and III, using a validated simultaneous HPLC-MS/MS
      assay.
AB  - A selective and sensitive high-performance liquid chromatography-electro-spray
      ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the
      simultaneous quantitative determination of Picroside-I, II, and III in rat plasma
      and tissue homogenate to aid the pre-clinical studies. The chromatographic
      separation was performed on a Hypersil GOLD AQ C18 column using a gradient
      elution program with a mobile phase consisting of 2mM ammonium acetate and
      acetonitrile. The detection was achieved using a triple quadrupole tandem MS in
      negative ionization multiple reaction monitoring (MRM) mode. One-step protein
      precipitation was selected for plasma and tissue sample preparation while liquid
      liquid extraction failed to achieve satisfactory recoveries. The calibration
      curves of all three analytes in either plasma or tissue homogenate showed good
      linearity over the concentration range of 0.5-500ng/mL with a limit of
      quantitation at 0.5ng/mL. Both the intra- and inter-day accuracy and precision
      were within +/-10%. The extraction recoveries were >70%, and the relative matrix
      effect ranged from 80.4% to 107.4% in all the biological samples. All the
      analytes were stable in matrices for at least 24h at room temperature, or 21 days
      in frozen. Three freeze/thaw cycles did not cause degradation. The method was
      successfully applied for quantification of the three iridoid glycosides in the
      collected plasma and various tissues following intravenous administration in
      rats. Picroside-I, II, and III were all eliminated rapidly with large volume of
      distribution. Among the three glycosides, Picroside-II showed the highest liver
      uptake, and only Picroside-I and II were found to get across the blood brain
      barrier (BBB). These results were consistent with their hepatoprotective or
      neuroprotective effects reported clinically. With the aid of the efficient and
      reliable simultaneous LC-ESI-MS/MS assay this pharmacokinetic study provided
      insights into their therapeutic targets of these three iridoid glycosides as well
      as valuable experimental basis for an expansion of their clinical indications. 

PMID- 25984966
TI  - Surface Engineering of Polypropylene Membranes with Carbonic Anhydrase-Loaded
      Mesoporous Silica Nanoparticles for Improved Carbon Dioxide Hydration.
AB  - Carbonic anhydrase (CA) is a native enzyme that facilitates the hydration of
      carbon dioxide into bicarbonate ions. This study reports the fabrication of thin
      films of active CA enzyme onto a porous membrane substrate using layer-by-layer
      (LbL) assembly. Deposition of multilayer films consisting of polyelectrolytes and
      CA was monitored by quartz crystal microgravimetry, while the enzymatic activity
      was assayed according to the rates of p-nitrophenylacetate (p-NPA) hydrolysis and
      CO2 hydration. The fabrication of the films onto a nonporous glass substrate
      showed CO2 hydration rates of 0.52 +/- 0.09 MUmol cm(-2) min(-1) per layer of
      bovine CA and 2.6 +/- 0.7 MUmol cm(-2) min(-1) per layer of a thermostable
      microbial CA. The fabrication of a multilayer film containing the microbial CA on
      a porous polypropylene membrane increased the hydration rate to 5.3 +/- 0.8 MUmol
      cm(-2) min(-1) per layer of microbial CA. The addition of mesoporous silica
      nanoparticles as a film layer prior to enzyme adsorption was found to increase
      the activity on the polypropylene membranes even further to a rate of 19 +/- 4
      MUmol cm(-2) min(-1) per layer of microbial CA. The LbL treatment of these
      membranes increased the mass transfer resistance of the membrane but decreased
      the likelihood of membrane pore wetting. These results have potential application
      in the absorption of carbon dioxide from combustion flue gases into aqueous
      solvents using gas-liquid membrane contactors. 

PMID- 25984967
TI  - Spatial mapping of the biologic effectiveness of scanned particle beams: towards
      biologically optimized particle therapy.
AB  - The physical properties of particles used in radiation therapy, such as protons,
      have been well characterized, and their dose distributions are superior to photon
      based treatments. However, proton therapy may also have inherent biologic
      advantages that have not been capitalized on. Unlike photon beams, the linear
      energy transfer (LET) and hence biologic effectiveness of particle beams varies
      along the beam path. Selective placement of areas of high effectiveness could
      enhance tumor cell kill and simultaneously spare normal tissues. However,
      previous methods for mapping spatial variations in biologic effectiveness are
      time-consuming and often yield inconsistent results with large uncertainties.
      Thus the data needed to accurately model relative biological effectiveness to
      guide novel treatment planning approaches are limited. We used Monte Carlo
      modeling and high-content automated clonogenic survival assays to spatially map
      the biologic effectiveness of scanned proton beams with high accuracy and
      throughput while minimizing biological uncertainties. We found that the
      relationship between cell kill, dose, and LET, is complex and non-unique.
      Measured biologic effects were substantially greater than in most previous
      reports, and non-linear surviving fraction response was observed even for the
      highest LET values. Extension of this approach could generate data needed to
      optimize proton therapy plans incorporating variable RBE. 

PMID- 25984968
TI  - Correction: Sequential conformational rearrangements in flavivirus membrane
      fusion.

PMID- 25984969
TI  - A Microfluidic Platform for the Rapid Determination of Distribution Coefficients
      by Gravity-Assisted Droplet-Based Liquid-Liquid Extraction.
AB  - The determination of pharmacokinetic properties of drugs, such as the
      distribution coefficient (D) is a crucial measurement in pharmaceutical research.
      Surprisingly, the conventional (gold standard) technique used for D measurements,
      the shake-flask method, is antiquated and unsuitable for the testing of valuable
      and scarce drug candidates. Herein, we present a simple microfluidic platform for
      the determination of distribution coefficients using droplet-based liquid-liquid
      extraction. For simplicity, this platform makes use of gravity to enable phase
      separation for analysis and is 48 times faster and uses 99% less reagents than
      performing an equivalent measurement using the shake-flask method. Furthermore,
      the D measurements achieved in our platform are in good agreement with literature
      values measured using traditional shake-flask techniques. Since D is affected by
      volume ratios, we use the apparent acid dissociation constant, pK', as a proxy
      for intersystem comparison. Our platform determines a pK' value of 7.24 +/- 0.15,
      compared to 7.25 +/- 0.58 for the shake-flask method in our hands and 7.21 for
      the shake-flask method in the literature. Devices are fabricated using injection
      molding, the batchwise fabrication time is <2 min per device (at a cost of $1
      U.S. per device), and the interdevice reproducibility is high. 

PMID- 25984970
TI  - Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G.
AB  - The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA
      based parasites including HIV-1. The viral infectivity factor (Vif) prevents
      restriction by triggering A3G degradation. Although the structure of the A3G
      catalytic domain is known, the structure of the N-terminal Vif-binding domain has
      proven more elusive. Here, we used evolution- and structure-guided mutagenesis to
      solubilize the Vif-binding domain of A3G, thus permitting structural
      determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered
      helical packing distinguish the structure from previous catalytic-domain
      structures and help to explain the reported inactivity of this domain. This
      soluble A3G N-terminal domain is bound by Vif; this enabled mutagenesis and
      biochemical experiments, which identified a unique Vif-interacting surface formed
      by the alpha1-beta1, beta2-alpha2 and beta4-alpha4 loops. This structure sheds
      new light on the Vif-A3G interaction and provides critical information for future
      drug development. 

PMID- 25984971
TI  - The proline-rich antimicrobial peptide Onc112 inhibits translation by blocking
      and destabilizing the initiation complex.
AB  - The increasing prevalence of multidrug-resistant pathogenic bacteria is making
      current antibiotics obsolete. Proline-rich antimicrobial peptides (PrAMPs)
      display potent activity against Gram-negative bacteria and thus represent an
      avenue for antibiotic development. PrAMPs from the oncocin family interact with
      the ribosome to inhibit translation, but their mode of action has remained
      unclear. Here we have determined a structure of the Onc112 peptide in complex
      with the Thermus thermophilus 70S ribosome at a resolution of 3.1 A by X-ray
      crystallography. The Onc112 peptide binds within the ribosomal exit tunnel and
      extends toward the peptidyl transferase center, where it overlaps with the
      binding site for an aminoacyl-tRNA. We show biochemically that the binding of
      Onc112 blocks and destabilizes the initiation complex, thus preventing entry into
      the elongation phase. Our findings provide a basis for the future development of
      this class of potent antimicrobial agents. 

PMID- 25984972
TI  - The mechanism of inhibition of protein synthesis by the proline-rich peptide
      oncocin.
AB  - Antibiotic-resistant bacteria are a global health issue necessitating the
      development of new effective therapeutics. Proline-rich antimicrobial peptides
      (PrAMPs), which include oncocins, are an extensively studied class of AMPs that
      counteract bacterial infection at submicromolar concentrations. Oncocins enter
      and kill bacteria by inhibiting certain targets rather than by acting through
      membrane lysis. Although they have recently been reported to bind DnaK and the
      bacterial ribosome, their mode of inhibition has remained elusive. Here we report
      the crystal structure of the oncocin derivative Onc112 bound to the Thermus
      thermophilus 70S ribosome. Strikingly, this 19-residue proline-rich peptide
      manifests the features of several known classes of ribosome inhibitors by
      simultaneously blocking the peptidyl transferase center and the peptide-exit
      tunnel of the ribosome. This high-resolution structure thus reveals the mechanism
      by which oncocins inhibit protein synthesis, providing an opportunity for
      structure-based design of new-generation therapeutics. 

PMID- 25984973
TI  - Serum IGFBP7 levels associate with insulin resistance and the risk of metabolic
      syndrome in a Chinese population.
AB  - Metabolic syndrome (MetS), one of the major public health concerns, is regarded
      as the "common soil" of incidence of common chronic diseases and may increase the
      risk of type 2 diabetes. The predominant underlying mechanism of MetS is insulin
      resistance (IR). Additionally, previous studies have indicated that IGFBP7 has
      high affinity of binding with insulin and might induce IR. The objective of this
      study was to firstly evaluate the associations of serum IGFBP7 levels with IR and
      MetS with a relatively large sample and population based design. In a population
      based MetS case-control study, HOMA-IR was used to evaluate the insulin
      sensitivity and serum IGFBP7 levels were determined with chemiluminescence-linked
      immunoassay. As a result, the subjects of MetS and IR had higher serum levels of
      IGFBP7 than control healthy subjects. High serum IGFBP7 levels increased the risk
      of MetS and IR. Serum IGFBP7 levels were also found to be significantly
      correlated with metabolic-associated parameters of Waist-to-hip ratio (WHR), HDL
      and LDL. These findings suggest that serum IGFBP7 levels are associated with IR
      and MetS, providing new insight into the mechanism of IR and Mets. IGFBP7 may be
      a potential interventional target for IR and Mets. 

PMID- 25984975
TI  - A Standardized Assessment of Functional Disability Predicts 1-year Mortality in
      Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt for Refractory
      Ascites.
AB  - GOALS: To determine the association between functional disability and mortality
      after transjugular intrahepatic portosystemic shunt (TIPS). BACKGROUND: TIPS is a
      common therapeutic procedure for cirrhotic patients with refractory ascites. The
      conventional metric for periprocedure risk stratification is the model for end
      stage liver disease (MELD), which uses biochemical parameters to predict post
      TIPS mortality. It does not account for functional disability. STUDY: This is a
      retrospective cohort study of 83 patients admitted at an academic liver
      transplant center with cirrhosis and refractory ascites for the purpose of TIPS
      placement. We assessed the association of patients' reported activities of daily
      living (ADL) on a scale of 1 to 21 before TIPS with a primary outcome of 1-year
      mortality. Multivariable regression to adjust for MELD and Child class was
      performed. RESULTS: A higher ADL score or functional independence, was associated
      with decreased 1-year mortality when modeled as both a continuous variable [odds
      ratio (OR), 0.80; 95% confidence interval (CI), 0.66-0.97; P=0.02) and a
      dichotomous variable (ADL 21 vs. <21; OR, 0.21; 95% CI, 0.05-0.70; P=0.01). After
      adjusting for MELD and Child class, functional independence was associated with
      decreased 1-year transplant-free mortality (OR, 0.22; 95% CI, 0.05-0.77; P=0.02).
      An ADL score consistent with dependence (<21) was significantly associated with a
      3.40-day (95% CI, 1.76-5.04) longer hospital stay, adjusting for MELD and Child
      class (P<0.0001). CONCLUSIONS: Functional disability is a predictor of post-TIPS
      mortality and length of stay after controlling for MELD.

PMID- 25984974
TI  - Targeting the Interleukin 6 Receptor to Treat Neuromyelitis Optica.

PMID- 25984976
TI  - Experience With Anti-TNF-alpha Biologic Agents in Succession in Patients With
      Crohn's Disease: A Retrospective Analysis of a Single Center.
AB  - GOALS: Our aim was to identify and compare the effectiveness of antitumor
      necrosis factor biologics when used as initial agents and when used in succession
      for the treatment of moderate to severe Crohn's disease (CD). BACKGROUND: Studies
      directly comparing the efficacy of biologics are lacking. When one biologic loses
      efficacy, patients are often treated with an alternate biologic. The
      effectiveness of this strategy has not been thoroughly investigated. STUDY: This
      is a retrospective cohort study from a database of 153 patients with CD treated
      with infliximab, adalimumab, or certolizumab pegol. Response rates determined by
      physician global assessment were compared between biologics when given as initial
      agents and after failure of 1 or 2 prior biologics. RESULTS: There were no
      significant differences in response between infliximab (64.5%), adalimumab
      (60.0%), and certolizumab pegol (66.7%) when given as initial biologics. As
      second-line or third-line agents after prior biologic failure, there was a trend
      toward increased response with infliximab (83.3%) versus adalimumab (52.7%) and
      certolizumab pegol (59.4%); however, this did not meet statistical significance.
      After failure or loss of response of 2 previous biologics, use of a third
      biologic was still effective with a response rate of 54.2%. CONCLUSIONS: All 3
      biologics have similar efficacy in the treatment of CD when given as initial
      agents. Infliximab has a trend toward increased response after prior biologic
      failure; however, this did not meet statistical significance. Even after loss of
      response or failure of 2 previous biologics, trial of a third alternate biologic
      is an effective strategy.

PMID- 25984977
TI  - Fecal Calprotectin as a Predictor of Relapse in Patients With Inflammatory Bowel
      Disease.

PMID- 25984979
TI  - Congenital Absence of Portal Vein With Cecal Varices.

PMID- 25984978
TI  - Nonalcoholic Fatty Liver Disease and Mean Platelet Volume: A Systemic Review and
      Meta-analysis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity,
      metabolic syndrome, and cardiovascular disease. Increased mean platelet volume
      (MPV), a marker of platelet activity, is associated with acute myocardial
      infarction, stroke, thrombosis, and increased mortality after myocardial
      infarction. The purpose of this study was to perform a meta-analysis to
      investigate the relationship between NAFLD and MPV. METHODOLOGY: A systematic
      search of MEDLINE (Ovid), PubMed, and CINAHL databases from 1950 to May 2014,
      complemented with manual review of references of published articles for studies
      comparing MPV in patients with and without NAFLD was done. Results were pooled
      using both fixed and random effects model. RESULTS: Our analysis from pooling of
      data from 8 observational studies including 1428 subjects (NAFLD=842 and non
      NAFLD=586) showed that MPV was significantly higher in patients with NAFLD than
      those without. The standardized mean difference in MPV between NAFLD and controls
      was 0.457 (95% confidence interval: 0.348-0.565, P<0.001) using fixed and 0.612
      (95% confidence interval: 0.286-0.938, P<0.001) using random effects model.
      CONCLUSIONS: This study suggests that MPV is significantly higher in patients
      with NAFLD, indicating the presence of increased platelet activity in such
      patients. Future research is needed to investigate whether this increased MPV is
      associated with increased cardiovascular disease in patients with NAFLD.

PMID- 25984981
TI  - A Unique Case of Noncirrhotic Portal Hypertension Secondary to Extrahepatic
      Sarcoidosis.

PMID- 25984980
TI  - A Large Multicenter Experience With Endoscopic Suturing for Management of
      Gastrointestinal Defects and Stent Anchorage in 122 Patients: A Retrospective
      Review.
AB  - GOALS: To describe a multicenter experience using an endoscopic suturing device
      for management of gastrointestinal (GI) defects and stent anchorage. BACKGROUND:
      Endoscopic closure of GI defects including perforations, fistulas, and
      anastomotic leaks as well as stent anchorage has improved with technological
      advances. An endoscopic suturing device (OverStitch; Apollo Endosurgery Inc.) has
      been used. STUDY: Retrospective study of consecutive patients who underwent
      endoscopic suturing for management of GI defects and/or stent anchorage were
      enrolled between March 2012 and January 2014 at multiple academic medical
      centers. Data regarding demographic information and outcomes including long-term
      success were collected. RESULTS: One hundred and twenty-two patients (mean age,
      52.6 y; 64.2% females) underwent endoscopic suturing at 8 centers for stent
      anchorage (n=47; 38.5%), fistulas (n=40; 32.7%), leaks (n=15; 12.3%), and
      perforations (n=20; 16.4%). A total of 44.2% underwent prior therapy and 97.5%
      achieved technical success. Immediate clinical success was achieved in 79.5%.
      Long-term clinical success was noted in 78.8% with mean follow-up of 68 days.
      Clinical success was 91.4% in stent anchorage, 93% in perforations, 80% in
      fistulas, but only 27% in anastomotic leak closure. CONCLUSIONS: Endoscopic
      suturing for management of GI defects and stent anchoring is safe and
      efficacious. Stent migration after stent anchoring was reduced compared with
      published data. Long-term success without further intervention was achieved in
      the majority of patients. The role of endoscopic suturing for repair of
      anastomotic leaks remains unclear given limited success in this retrospective
      study.

PMID- 25984982
TI  - Effect of thiols, zinc, and redox conditions on Hg uptake in Shewanella
      oneidensis.
AB  - Mercury uptake in bacteria represents a key first step in the production and
      accumulation of methylmercury in biota. Previous experiments with mercury
      methylating bacteria have shown that Hg uptake is enhanced by some thiols, in
      particular cysteine, and that it is an energy-dependent process through heavy
      metal transporters [Schaefer et al. Environ. Sci. Technol. 2014, 48, 3007]. In
      this study, we examine Hg uptake in the nonmethylating facultative aerobe,
      Shewanella oneidensis, under both anaerobic and aerobic conditions. Our results
      demonstrate similar characteristics of the Hg uptake system to those of the Hg
      methylating strains: (1) uptake is enhanced in the presence of some thiols but
      not others; (2) uptake is energy dependent as evidenced by inhibition by a
      protonophore, and (3) uptake is inhibited by high Zn(II) concentrations. Initial
      cellular uptake rates in S. oneidensis were remarkably similar under aerobic and
      fumarate-reducing conditions. These data support a similar Hg(II) uptake
      mechanism within the proteobacteria of accidental Hg(II) transport through heavy
      metal transporters with similar rates of uptake but differences in the ability to
      take up Hg bound to different thiols.

PMID- 25984983
TI  - Iron-coupled inactivation of phosphorus in sediments by macrozoobenthos
      (chironomid larvae) bioturbation: Evidences from high-resolution dynamic
      measurements.
AB  - The effects of chironomid larvae bioturbation on the lability of phosphorus (P)
      in sediments were investigated through sediment incubation for 140 days. High
      resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT)
      techniques were applied to obtain soluble and labile P/Fe profiles at a
      millimeter resolution, respectively. The larvae bioturbation decreased
      concentrations of soluble/labile P and Fe by up to over half of the control at
      the sediment depths of influence up to 70 and 90 mm respectively. These effects
      continued over 116 days and disappeared on the 140th days due to eclosion of
      chironomid larvae. Labile P was highly correlated with labile Fe, while a weak
      correlation was observed between soluble P and soluble Fe. It was concluded that
      Fe(II) oxidation and its enhanced adsorption were the major mechanisms
      responsible for the decreases of soluble and labile P. 

PMID- 25984984
TI  - Maternal exposure to alkali, alkali earth, transition and other metals:
      Concentrations and predictors of exposure.
AB  - Most studies of metals exposure focus on the heavy metals. There are many other
      metals (the transition, alkali and alkaline earth metals in particular) in common
      use in electronics, defense industries, emitted via combustion and which are
      naturally present in the environment, that have received limited attention in
      terms of human exposure. We analysed samples of whole blood (172), urine (173)
      and drinking water (172) for antimony, beryllium, bismuth, cesium, gallium,
      rubidium, silver, strontium, thallium, thorium and vanadium using ICPMS. In
      general most metals concentrations were low and below the analytical limit of
      detection with some high concentrations observed. Few factors examined in
      regression models were shown to influence biological metals concentrations and
      explained little of the variation. Further study is required to establish the
      source of metals exposures at the high end of the ranges of concentrations
      measured and the potential for any adverse health impacts in children. 

PMID- 25984985
TI  - Transcriptional responses of earthworm (Eisenia fetida) exposed to naphthenic
      acids in soil.
AB  - In this study, earthworms (Eisenia fetida) were exposed to commercial NAs
      contaminated soil, and changes in the levels of reactive oxygen species (ROS) and
      gene expressions of their defense system were monitored. The effects on the gene
      expression involved in reproduction and carcinogenesis were also evaluated.
      Significant increases in ROS levels was observed in NAs exposure groups, and the
      superoxide dismutase (SOD) and catalase (CAT) genes were both up-regulated at low
      and medium exposure doses, which implied NAs might exert toxicity by oxidative
      stress. The transcription of CRT and HSP70 coincided with oxidative stress, which
      implied both chaperones perform important functions in the protection against
      oxidative toxicity. The upregulation of TCTP gene indicated a potential adverse
      effect of NAs to terrestrial organisms through induction of carcinogenesis, and
      the downregulation of ANN gene indicated that NAs might potentially result in
      deleterious reproduction effects. 

PMID- 25984986
TI  - Simultaneous full-field 3-D vibrometry of the human eardrum using spatial
      bandwidth multiplexed holography.
AB  - Holographic interferometric methods typically require the use of three
      sensitivity vectors in order to obtain three-dimensional (3-D) information.
      Methods based on multiple directions of illumination have limited applications
      when studying biological tissues that have temporally varying responses such as
      the tympanic membrane (TM). Therefore, to measure 3-D displacements in such
      applications, the measurements along all the sensitivity vectors have to be done
      simultaneously. We propose a multiple-illumination directions approach to measure
      3-D displacements from a single-shot hologram that contains displacement
      information from three sensitivity vectors. The hologram of an object of interest
      is simultaneously recorded with three incoherently superimposed pairs of
      reference and object beams. The incident off-axis angles of the reference beams
      are adjusted such that the frequency components of the multiplexed hologram are
      completely separate. Because of the differences in the directions and wavelengths
      of the reference beams, the positions of each reconstructed image corresponding
      to each sensitivity vector are different. We implemented a registration algorithm
      to accurately translate individual components of the hologram into a single
      global coordinate system to calculate 3-D displacements. The results include
      magnitudes and phases of 3-D sound-induced motions of a human cadaveric TM at
      several excitation frequencies showing modal and traveling wave motions on its
      surface.

PMID- 25984987
TI  - Chemical intervention in bacterial lignin degradation pathways: Development of
      selective inhibitors for intradiol and extradiol catechol dioxygenases.
AB  - Bacterial lignin degradation could be used to generate aromatic chemicals from
      the renewable resource lignin, provided that the breakdown pathways can be
      manipulated. In this study, selective inhibitors of enzymatic steps in bacterial
      degradation pathways were developed and tested for their effects upon lignin
      degradation. Screening of a collection of hydroxamic acid metallo-oxygenase
      inhibitors against two catechol dioxygenase enzymes, protocatechuate 3,4
      dioxygenase (3,4-PCD) and 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB),
      resulted in the identification of selective inhibitors D13 for 3,4-PCD (IC50
      15MUM) and D3 for MhpB (IC50 110MUM). Application of D13 to Rhodococcus jostii
      RHA1 in minimal media containing ferulic acid led to the appearance of metabolic
      precursor protocatechuic acid at low concentration. Application of 1mM
      disulfiram, an inhibitor of mammalian aldehyde dehydrogenase, to R. jostii RHA1,
      gave rise to 4-carboxymuconolactone on the beta-ketoadipate pathway, whereas in
      Pseudomonas fluorescens Pf-5 disulfiram treatment gave rise to a metabolite found
      to be glycine betaine aldehyde. 

PMID- 25984988
TI  - Informed Decision Making for Percutaneous Coronary Intervention for Stable
      Coronary Disease.
AB  - IMPORTANCE: Patients with stable coronary disease undergoing percutaneous
      coronary intervention (PCI) are frequently misinformed about the benefits of PCI.
      Little is known about the quality of decision making before angiography and
      possible PCI. OBJECTIVE: To assess the quality of informed decision making and
      its association with patient decisions. DESIGN, SETTING, AND PARTICIPANTS: We
      performed a cross-sectional analysis of recorded conversations between August 1,
      2008, and August 31, 2012, among adults with known or suspected stable coronary
      disease at outpatient cardiology practices. MAIN OUTCOMES AND MEASURES: Presence
      of 7 elements of informed decision making and the decision to undergo angiography
      and possible PCI. RESULTS: Of 59 conversations conducted by 23 cardiologists, 2
      (3%) included all 7 elements of informed decision making; 8 (14%) met a more
      limited definition of procedure, alternatives, and risks. Specific elements
      significantly associated with not choosing angiography and possible PCI included
      discussion of uncertainty (odds ratio [OR], 20.5; 95% CI, 2.3-204.9), patient's
      role (OR, 5.3; 95% CI, 1.3-21.3), exploration of alternatives (OR, 9.5; 95% CI,
      2.5-36.5), and exploration of patient preference (OR, 4.8; 95% CI, 1.2-19.4).
      Neither the presence of angina nor severity of symptoms was associated with
      choosing angiography and possible PCI. In a multivariable analysis using the
      total number of elements as a predictor, better informed patients were less
      likely to choose angiography and possible PCI (OR per additional element, 3.2;
      95% CI, 1.4-7.1; P = .005). CONCLUSIONS AND RELEVANCE: In conversations between
      cardiologists and patients with stable angina, informed decision making is often
      incomplete. More complete discussions are associated with patients choosing not
      to undergo angiography and possible PCI.

PMID- 25984989
TI  - Sea Cucumbers Metabolites as Potent Anti-Cancer Agents.
AB  - Sea cucumbers and their extracts have gained immense popularity and interest
      among researchers and nutritionists due to their nutritive value, potential
      health benefits, and use in the treatment of chronic inflammatory diseases. Many
      areas of the world use sea cucumbers in traditional foods and folk medicine.
      Though the actual components and their specific functions still remain to be
      investigated, most sea cucumber extracts are being studied for their anti
      inflammatory functions, immunostimulatory properties, and for cancer prevention
      and treatment. There is large scope for the discovery of additional bioactive,
      valuable compounds from this natural source. Sea cucumber extracts contain unique
      components, such as modified triterpene glycosides, sulfated polysaccharides,
      glycosphingolipids, and esterified phospholipids. Frondanol A5, an isopropyl
      alcohol/water extract of the enzymatically hydrolyzed epithelia of the edible
      North Atlantic sea cucumber, Cucumaria frondosa, contains monosulfated
      triterpenoid glycoside Frondoside A, the disulfated glycoside Frondoside B, the
      trisulfated glycoside Frondoside C, 12-methyltetradecanoic acid, eicosapentaenoic
      acid, and fucosylated chondroitin sulfate. We have extensively studied the
      efficacy of this extract in preventing colon cancer in rodent models. In this
      review, we discuss the anti-inflammatory, immunostimulatory, and anti-tumor
      properties of sea cucumber extracts. 

PMID- 25984991
TI  - A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase
      Activating Protein Based on Rab7 as a Substrate.
AB  - APSL (active peptide from shark liver) is a hepatic stimulator cytokine from the
      liver of Chiloscyllium. It can effectively protect islet cells and improve
      complications in mice with alloxan-induced diabetes. Here, we demonstrate that
      the APSL sequence is present in the N-terminus of novel TBC (Tre-2, Bub2 and
      Cdc16) domain family, member 15 (TBC1D15) from Chiloscyllium plagiosum. This
      shark TBC1D15 gene, which contains an ORF of 2088 bp, was identified from a cDNA
      library of regenerating shark liver. Bioinformatic analysis showed that the gene
      is highly homologous to TBC1D15 genes from other species. Moreover, the N
      terminus of shark TBC1D15 contains a motif of unknown function (DUF3548), which
      encompasses the APSL fragment. Rab-GAP activity analysis showed that shark
      TBC1D15 is a new member of the TBC1D15 family. These results demonstrated that
      shark TBC1D15 possesses Rab-GAP activity using Rab7 as a substrate, which is a
      common property of the TBC1D15 family. The involvement of APSL at the N-terminus
      of TBC1D15 also demonstrates that this protein might be involved in insulin
      signaling and may be associated with the development of type 2 diabetes. The
      current findings pave the way for further functional and clinical studies of
      these proteins from marine sources. 

PMID- 25984992
TI  - Impact of Nanostructure on Mechanical Properties of Norbornene-based Block
      Copolymers under Simulated Operating Conditions for Biobutanol Membranes.
AB  - The structure and mechanical properties of a novel block copolymer (BCP) system
      with T(g)'s for both segments exceeding 300  degrees C, poly(butylnorbornene)
      block-poly(hydroxyhexafluoroisopropyl norbornene) (BuNB-b-HFANB), are
      investigated as a function of processing conditions used for solvent vapor
      annealing (SVA). Solvent selection impacts long-range order markedly, but
      unexpectedly vertical orientation of cylinders are preferred over a wide range of
      solubility parameters, as determined by atomic force microscopy and grazing
      incidence small-angle X-ray scattering. The mechanical properties (elastic
      modulus, fracture strength, and onset fracture strain) are dependent upon the
      long-range order induced during SVA and determined using the combination of
      surface wrinkling and cracking. The modulus and fracture strength of the films
      increase from 1.44 GPa and 12.1 MPa to 1.77 GPa and 17.5 MPa, respectively,
      whereas the onset fracture strain decreases from 1.6% to approximately 0.6% as
      the ordering is improved. The polarity difference in the segments of the BCP is
      attractive for membrane separations, especially butanol-water. For biobutanol
      recovery, the titers are typically <3 wt % butanol; exposure of the BCP membrane
      to aqueous 1 wt % butanol decreases the elastic modulus to approximately 0.90
      GPa, irrespective of the morphology, despite the high T(g) of both segments and
      limited swelling (5.0 wt %). Correspondingly, the onset fracture strain of these
      swollen films is estimated to increase significantly to 6-7%. These results
      indicate that operating conditions impact the mechanical performance of BCP
      membranes more than their morphology despite the high T(g) of the neat copolymer.
      Wrinkling and cracking provide a facile route to test the mechanical properties
      of membranes under simulated operando conditions.

PMID- 25984990
TI  - Emerging concepts promising new horizons for marine biodiscovery and synthetic
      biology.
AB  - The vast oceans of the world, which comprise a huge variety of unique ecosystems,
      are emerging as a rich and relatively untapped source of novel bioactive
      compounds with invaluable biotechnological and pharmaceutical potential. Evidence
      accumulated over the last decade has revealed that the diversity of marine
      microorganisms is enormous with many thousands of bacterial species detected that
      were previously unknown. Associated with this diversity is the production of
      diverse repertoires of bioactive compounds ranging from peptides and enzymes to
      more complex secondary metabolites that have significant bioactivity and thus the
      potential to be exploited for innovative biotechnology. Here we review the
      discovery and functional potential of marine bioactive peptides such as
      lantibiotics, nanoantibiotics and peptidomimetics, which have received particular
      attention in recent years in light of their broad spectrum of bioactivity. The
      significance of marine peptides in cell-to-cell communication and how this may be
      exploited in the discovery of novel bioactivity is also explored. Finally, with
      the recent advances in bioinformatics and synthetic biology, it is becoming clear
      that the integration of these disciplines with genetic and biochemical
      characterization of the novel marine peptides, offers the most potential in the
      development of the next generation of societal solutions. 

PMID- 25984994
TI  - Wide-ranging cognitive deficits in adolescents following early life maltreatment.
AB  - OBJECTIVE: Studies of adolescents with histories of maltreatment typically report
      specific cognitive deficits in higher order functioning and attention. Emerging
      evidence suggests that the cognitive difficulties seen in maltreated adolescents
      are much broader, and go beyond executive functioning impairments. This study
      examined whether maltreated adolescents exhibited cognitive deficits across a
      number of cognitive domains, in addition to executive functioning. METHOD: A
      group of 39 adolescents with documented histories of severe maltreatment were
      compared with 43 controls on measures of learning and memory, executive function,
      processing speed, working memory, visuoperceptual function, and language. Groups
      were matched demographically and on the Wechsler Intelligence Scale for Children
      IV (WISC-IV) Full Scale Intelligence Quotient (FSIQ; Wechsler, 2003). RESULTS:
      Using multivariate analyses, the maltreated group showed significant impairments
      on measures of executive function and attention, working memory, learning,
      visuospatial function and visual processing speed. Effect sizes ranged from
      medium to large. CONCLUSIONS: The FSIQ indicated that these adolescents were
      performing comparably with their nonmaltreated peers, though this was not the
      case when specific cognitive functions were measured. This demonstrates that
      maltreated adolescents are more likely to have a range of cognitive deficits that
      can only be identified with thorough neuropsychological assessment. Such deficits
      have the potential to significantly impair adaptive, social, emotional, and
      academic functioning, explaining many of the typical difficulties seen in
      maltreated adolescents.

PMID- 25984993
TI  - DNA vaccines, electroporation and their applications in cancer treatment.
AB  - Numerous animal studies and recent clinical studies have shown that
      electroporation-delivered DNA vaccines can elicit robust Ag-specific CTL
      responses and reduce disease severity. However, cancer antigens are generally
      poorly immunogenic, requiring special conditions for immune response induction.
      To date, many different approaches have been used to elicit Ag-specific CTL and
      anti-neoplastic responses to DNA vaccines against cancer. In vivo electroporation
      is one example, whereas others include DNA manipulation, xenogeneic antigen use,
      immune stimulatory molecule and immune response regulator application, DNA prime
      boost immunization strategy use and different DNA delivery methods. These
      strategies likely increase the immunogenicity of cancer DNA vaccines, thereby
      contributing to cancer eradication. However, cancer cells are heterogeneous and
      might become CTL-resistant. Thus, understanding the CTL resistance mechanism(s)
      employed by cancer cells is critical to develop counter-measures for this immune
      escape. In this review, the use of electroporation as a DNA delivery method, the
      strategies used to enhance the immune responses, the cancer antigens that have
      been tested, and the escape mechanism(s) used by tumor cells are discussed, with
      a focus on the progress of clinical trials using cancer DNA vaccines. 

PMID- 25984995
TI  - Delay discounting is greater among drug users seropositive for hepatitis C but
      not HIV.
AB  - OBJECTIVE: Substance dependent individuals (SDIs) typically overvalue immediate
      and undervalue (discount) delayed rewards, and level of discounting significantly
      predicts posttreatment relapse and other behavioral outcomes. Delay discounting
      has potential significance for studies of HIV prevention and adherence to
      antiretroviral therapy; but effects of HIV infection on delay discounting rates
      among SDIs are not well understood, although discounting rates are higher among
      individuals infected with hepatitis C virus (HCV). In this study, we investigated
      potential additive or interactive effects of HIV and HCV infection on delay
      discounting performance among a group of 239 SDIs with verified HIV and HCV
      serostatus. METHOD: All participants were verified abstinent from drugs and
      alcohol at testing. All participants completed measures of substance abuse
      characteristics and comorbid disorders, and the Monetary Choice Questionnaire, a
      well-known measure used to derive k coefficients, which index discounting rates.
      RESULTS: Groups were comparable on demographic, substance use, and comorbid
      characteristics. Compared with uninfected controls, discounting rates were
      significantly higher among individuals seropositive for HCV but not HIV.
      Additionally, no significant group differences in discounting rates were observed
      among HCV+ participants with or without coinfection with HIV. Group differences
      could not be attributed to aging or nonspecific effects of drug addiction.
      Additionally, increased discounting rates were associated with riskier injection
      practices. CONCLUSIONS: Potential mechanisms contributing to this discrepancy in
      discounting rates between HIV+ and HCV+ SDIs, including decision making, are
      discussed and await further study.

PMID- 25984996
TI  - Commentary: neurodegeneration and sport.

PMID- 25984999
TI  - Boo! Fear generalization in the primate amygdala.

PMID- 25985000
TI  - Time is brain and so is less blood: the hyperacute period after intracerebral
      hemorrhage.

PMID- 25985001
TI  - All hands on deck: the importance of additional pathways in mediating recovery in
      spinal cord injury.

PMID- 25985002
TI  - Long-term Outcomes of the International Randomized Clinical Trial of Stenting
      Versus Endarterectomy for Symptomatic Carotid Artery Stenosis.

PMID- 25985003
TI  - ESCAPE Trial Supports Rapid Endovascular Thrombectomy in the Management of Large
      Vessel Acute Ischemic Stroke.

PMID- 25985004
TI  - Outcomes of the ACT III Study: Rindopepimut (CDX-110) Therapy for Glioblastoma.

PMID- 25985005
TI  - Periostin: a potential target for glioblastoma multiforme treatment.

PMID- 25985008
TI  - E-dura: A Novel Neural Interface Device.

PMID- 25985009
TI  - Factors Influencing Quality of Life in Adult End-Stage Renal Disease Patients
      Undergoing Hemodialysis.
AB  - BACKGROUND: The population of individuals with end-stage renal disease (ESRD) in
      Korea is increasing rapidly, yet comprehensive research on the quality of life
      (QOL) of this population undergoing hemodialysis is scarce. PURPOSE: The purpose
      of this study was to identify the factors influencing QOL of Korean hemodialysis
      patients with ESRD. METHODS: This study was a cross-sectional survey. Data were
      drawn from a convenience sample of 141 patients aged >18 years receiving
      maintenance hemodialysis in a general hospital. Data were collected by a self
      administrated survey conducted from June 15 to July 25, 2012. The questionnaire
      included basic subject data, QOL, fatigue, perceived health status, and emotional
      status. RESULTS: The mean QOL score was 3.09 or "above average" as measured by
      the World Health Organization's (1993) Quality of Life Assessment. Significant
      differences were observed for basic subject data including educational level,
      occupation, monthly income, medical expense assistance, and family living
      situation. Significant negative correlations were found between QOL and fatigue
      and between anxiety and depression, but a significant positive correlation was
      found with perceived health status. The factors influencing QOL were fatigue and
      depression, marital status (married), and medical expense assistance (from self
      or parents). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of this study
      indicate that, to improve the QOL in patients with ESRD, comprehensive
      intervention is necessary to assess and manage depression and fatigue. Social
      mediation is needed to enhance the QOL of patients with ESRD who lack familial
      and economic support, those who are single, or those who cannot afford medical
      expenses either by themselves or with the help of their parents.

PMID- 25985010
TI  - HTT/Huntingtin in selective autophagy and Huntington disease: A foe or a friend
      within?

PMID- 25985012
TI  - Distinct cardiac phenotype between two homozygotes born in a village with
      accumulation of a genetic deficiency of adipose triglyceride lipase.

PMID- 25985013
TI  - Predictive value of galectin-3 for incident cardiovascular disease and heart
      failure in the population-based FINRISK 1997 cohort.
AB  - OBJECTIVES: Galectin-3 is an emerging biomarker playing an important, complex
      role in intracellular pathways of cardiovascular diseases and heart failure. We
      aimed therefore to investigate the predictive value of galectin-3 for incident
      cardiovascular disease and heart failure. METHODS: Galectin-3 levels were
      measured in 8444 participants of the general population-based FINRISK 1997
      cohort. Cox proportional hazards regression analyses, adjusting for traditional
      Framingham risk factors, prevalent valvular heart disease, eGFR (estimated
      glomerular filtration rate) as well as NT-proBNP, were used to examine the
      predictive power of galectin-3. Measurements of discrimination and
      reclassification using 10-fold cross-validation were performed to control for
      over-optimism. Cardiovascular death (CD), all-cause mortality, myocardial
      infarction (MI), ischemic stroke (hemorrhagic strokes were excluded) and heart
      failure (HF) were used as endpoints. RESULTS: During the follow-up of up to 15
      years there were in total 1136 deaths from any cause, 383 cardiac deaths, 359
      myocardial infarctions, 401 ischemic strokes and 641 cases of incident heart
      failure. Hazard ratios (HR) were statistically significant for all-cause
      mortality (1.12, p < 0.001), cardiac death (1.15, p = 0.033) and heart failure
      (1.10, p = 0.049). Statistical significance was lost when analyzing by gender
      except for all-cause mortality. No significant improvements were observed in
      model discrimination or overall reclassification upon inclusion of galectin-3.
      Compared to NT-proBNP, the predictive power of galectin-3 was weaker but both
      remained significant, independently of each other. CONCLUSION: Galectin-3 levels
      were predictive for future cardiovascular events but improvements in
      discrimination and reclassifications were modest.

PMID- 25985014
TI  - Is ganglionated plexi ablation during Maze IV procedure beneficial for
      postoperative long-term stable sinus rhythm?
AB  - BACKGROUND: We investigated the role of surgical ablation targeting the
      autonomous nervous system during a Cox-Maze IV procedure in the maintenance of
      sinus rhythm at long-term follow-up. METHODS: The patient population consisted of
      519 subjects with persistent or long-standing persistent atrial fibrillation (AF)
      undergoing radiofrequency Maze IV during open heart surgery between January 2006
      and July 2013 at three institutions without (Group 1) or with (Group 2)
      ganglionated plexi (GP) ablation. Recurrence of atrial fibrillation off
      antiarrhythmic drugs was the primary outcome. Predictors of AF recurrence were
      evaluated by means of competing risk regression. Median follow-up was 36.7
      months. RESULTS: The percentage of patients in normal sinus rhythm (NSR) off
      antiarrhythmic drugs did not differ between groups (Group 1-75.5%, Group 2-67.8%,
      p = 0.08). Duration of AF >= 38 months (p = 0.01), left atrial diameter >= 54 mm
      (0.001), left atrial area >= 33 cm(2) (p = 0.005), absence of connecting lesions
      (p= 0.04), and absence of right atrial ablation (p < 0.001) were independently
      associated with high incidence of AF recurrence. In contrast the absence of GP
      ablation was not a significant factor (p = 0.12). CONCLUSIONS: GP ablation did
      not prove to be beneficial for postoperative stable NSR. A complete left atrial
      lesion set and biatrial ablation are advisable for improving rhythm outcomes.
      Randomized controlled trials are necessary to confirm our findings.

PMID- 25985015
TI  - Short-term effects of air pollution on out-of-hospital cardiac arrest in
      Shenzhen, China.

PMID- 25985011
TI  - Outcomes of primary percutaneous coronary interventions in nonagenarians with
      acute myocardial infarction.
AB  - BACKGROUND: Few data are available on primary percutaneous coronary intervention
      (pPCI) in nonagenarians. In a large prospective registry on pPCI for STEMI we
      compared the demographics, procedural and in-hospital outcomes between
      nonagenarians (age >= 90 years) and patients aged < 90 years. METHODS AND
      RESULTS: We included 26,157 consecutive patients with pPCI in the Greater Paris
      Area region between 2003 and 2011. Of these, 418 (1.6%) were >= 90 years old.
      Nonagenarians (versus patients < 90 years) were more likely to be female (62.3%
      versus 22.5%, p < 0.0001), nonsmokers (81.6% versus 36.7%, p < 0.0001), in
      cardiogenic shock (Killip IV) upon admission (10.5% versus 4.8%, p < 0.001), and
      had significant co-morbidities. Over two-thirds of patients underwent procedures
      via the radial artery (61% versus 72.1%, p = 0.007). Both groups had high and
      similar angiographic success rates (98.1% versus 98.7%, p = 0.33). Drug-eluting
      stents were used less often in nonagenarians (4.4% versus 16.7%, p < 0.0001).
      Hospital mortality was significantly much higher in patients over 90 years old
      (24.9% versus 5.1%, p < 0.001) in univariate analysis. After adjustment for sex,
      cardiogenic shock, diabetes, triple vessel disease, drug-eluting stent use and
      glycoprotein IIb/IIIa inhibitors use, mortality remains higher in nonagenarian
      patients (OR: 4.31; 95% CI: 3.26-5.71, p < 0.0001). CONCLUSIONS: In a real-world
      setting, we found important demographic differences in nonagenarian compared to
      younger patients. Despite achieving a high rate of reperfusion with pPCI using
      mainly radial access, similar to that achieved in younger patients, hospital
      mortality was higher in nonagenarians.

PMID- 25985016
TI  - Relationship Among Signal Fidelity, Hearing Loss, and Working Memory for Digital
      Noise Suppression.
AB  - OBJECTIVES: This study considered speech modified by additive babble combined
      with noise-suppression processing. The purpose was to determine the relative
      importance of the signal modifications, individual peripheral hearing loss, and
      individual cognitive capacity on speech intelligibility and speech quality.
      DESIGN: The participant group consisted of 31 individuals with moderate high
      frequency hearing loss ranging in age from 51 to 89 years (mean = 69.6 years).
      Speech intelligibility and speech quality were measured using low-context
      sentences presented in babble at several signal-to-noise ratios. Speech stimuli
      were processed with a binary mask noise-suppression strategy with systematic
      manipulations of two parameters (error rate and attenuation values). The
      cumulative effects of signal modification produced by babble and signal
      processing were quantified using an envelope-distortion metric. Working memory
      capacity was assessed with a reading span test. Analysis of variance was used to
      determine the effects of signal processing parameters on perceptual scores.
      Hierarchical linear modeling was used to determine the role of degree of hearing
      loss and working memory capacity in individual listener response to the processed
      noisy speech. The model also considered improvements in envelope fidelity caused
      by the binary mask and the degradations to envelope caused by error and noise.
      RESULTS: The participants showed significant benefits in terms of intelligibility
      scores and quality ratings for noisy speech processed by the ideal binary mask
      noise-suppression strategy. This benefit was observed across a range of signal-to
      noise ratios and persisted when up to a 30% error rate was introduced into the
      processing. Average intelligibility scores and average quality ratings were well
      predicted by an objective metric of envelope fidelity. Degree of hearing loss and
      working memory capacity were significant factors in explaining individual
      listener's intelligibility scores for binary mask processing applied to speech in
      babble. Degree of hearing loss and working memory capacity did not predict
      listeners' quality ratings. CONCLUSIONS: The results indicate that envelope
      fidelity is a primary factor in determining the combined effects of noise and
      binary mask processing for intelligibility and quality of speech presented in
      babble noise. Degree of hearing loss and working memory capacity are significant
      factors in explaining variability in listeners' speech intelligibility scores but
      not in quality ratings.

PMID- 25985017
TI  - Bilateral Loudness Balancing and Distorted Spatial Perception in Recipients of
      Bilateral Cochlear Implants.
AB  - OBJECTIVE: To determine whether bilateral loudness balancing during mapping of
      bilateral cochlear implants (CIs) produces fused, punctate, and centered auditory
      images that facilitate lateralization with stimulation on single-electrode pairs.
      DESIGN: Adopting procedures similar to those that are practiced clinically,
      direct stimulation was used to obtain most-comfortable levels (C levels) in
      recipients of bilateral CIs. Three pairs of electrodes, located in the base,
      middle, and apex of the electrode array, were tested. These electrode pairs were
      loudness-balanced by playing right-left electrode pairs sequentially. In
      experiment 1, the authors measured the location, number, and compactness of
      auditory images in 11 participants in a subjective fusion experiment. In
      experiment 2, the authors measured the location and number of the auditory images
      while imposing a range of interaural level differences (ILDs) in 13 participants
      in a lateralization experiment. Six of these participants repeated the mapping
      process and lateralization experiment over three separate days to determine the
      variability in the procedure. RESULTS: In approximately 80% of instances,
      bilateral loudness balancing was achieved from relatively small adjustments to
      the C levels (<=3 clinical current units). More important, however, was the
      observation that in 4 of 11 participants, simultaneous bilateral stimulation
      regularly elicited percepts that were not fused into a single auditory object.
      Across all participants, approximately 23% of percepts were not perceived as
      fused; this contrasts with the 1 to 2% incidence of diplacusis observed with
      normal-hearing individuals. In addition to the unfused images, the perceived
      location was often offset from the physical ILD. On the whole, only 45% of
      percepts presented with an ILD of 0 clinical current units were perceived as
      fused and heard in the center of the head. Taken together, these results suggest
      that distortions to the spatial map remain common in bilateral CI recipients even
      after careful bilateral loudness balancing. CONCLUSIONS: The primary conclusion
      from these experiments is that, even after bilateral loudness balancing,
      bilateral CI recipients still regularly perceive stimuli that are unfused, offset
      from the assumed zero ILD, or both. Thus, while current clinical mapping
      procedures for bilateral CIs are sufficient to enable many of the benefits of
      bilateral hearing, they may not elicit percepts that are thought to be optimal
      for sound-source location. As a result, in the absence of new developments in
      signal processing for CIs, new mapping procedures may need to be developed for
      bilateral CI recipients to maximize the benefits of bilateral hearing.

PMID- 25985018
TI  - Meta-Analysis of Distortion Product Otoacoustic Emission Retest Variability for
      Serial Monitoring of Cochlear Function in Adults.
AB  - OBJECTIVE: Distortion product otoacoustic emissions (DPOAEs) have long been
      heralded as a means to objectively monitor cochlear function and increasingly are
      becoming a key component in hearing surveillance programs for individuals at risk
      for ototoxic- and occupational noise-related hearing loss. Yet clinicians are
      unsure how to define clinically meaningful shifts in DPOAE level. In this study,
      a meta-analysis approach is used to synthesize the DPOAE level test-retest
      literature to construct a set of DPOAE level shift reference limits that can be
      used clinically to define a statistically significant emission change. DESIGN:
      The authors reviewed all published articles identified through a Medline search
      using the terms "Otoacoustic Emission Variability," "Otoacoustic Emission
      Reliability," "Otoacoustic Emission Repeatability," and "Otoacoustic Emission
      Test Retest" restricted to DPOAEs, adults, and English language. Articles with
      DPOAE level data elicited by moderate stimulus levels for f2 frequencies of 1000,
      2000, 4000, or 6000 Hz were selected because these stimulus parameters were
      relatively well represented in the literature. The authors only included articles
      that reported the standard error of the measurement (SEM) or from which the SEM
      could be calculated. Meta-analysis was used to estimate the population mean SEM
      over the included studies. Models were fit separately for each f2 primary and
      included days since baseline and study-specific random effects. RESULTS: Ten
      DPOAE test-retest studies met inclusion criteria for this meta-analysis. The SEM
      values varied widely across published studies (0.57 to 3.9 dB) and were provided
      for relatively short time intervals (less than 15 days on average). Time, or days
      since baseline, was statistically significant at higher f2 frequencies (4000 and
      6000 Hz). From the model results, 90% reference limits specific to the f2 and
      elapsed time between baseline and follow-up measurements were established.
      Reference limits provided correspond to negative (emission decrement) and
      positive (emission enhancement) shifts indicative of the amount of measurement
      variability that, using this approach, must be tolerated as "normal" fluctuations
      over time. Changes larger than the reference limits are considered significant
      and warrant follow-up testing. CONCLUSIONS: The meta-analysis presented provides
      reference limits that are appropriate for a set of specific f2 frequencies and
      time intervals. The meta-analysis concerns the SEM statistic directly, so that
      any preferred reference limit can be computed from the results and should be
      predicated upon the screening application. The presumed advantage of this meta
      analytic approach is increased precision relative to limits suggested by any of
      the individual studies included in the analysis.

PMID- 25985020
TI  - Controlled synthesis of organic ligand passivated ZnO nanostructures and their
      photocatalytic activity under visible light irradiation.
AB  - Zinc oxide (ZnO) nanostructures were synthesized and their photocatalytic
      activity was evaluated using methylene blue (MB) as a model pollutant.
      Ethylenediamine (EDA) was used as a passivating agent to control the morphology
      and size of the ZnO nanostructures. In the absence of EDA, agglomerated ZnO
      nanoparticles were obtained. The addition of EDA at varying concentrations
      considerably influenced the morphological size. The as-prepared samples were
      extensively characterized using various techniques. The morphology- and size
      dependent photocatalytic degradation of MB was studied under visible light
      irradiation. The maximum degradation efficiency was observed for ZnO nanoflakes;
      the MB-related absorbance peak completely disappeared after 15 min of
      irradiation. Furthermore, the effect of various photocatalytic reaction
      parameters, such as pH (3-12) of the solution, the concentration of the dye (5,
      10, 15, and 20 ppm), and the dosage of the photocatalyst (25, 50, 75, and 100 mg
      L(-1)), on the photodegradation of MB was investigated to determine the maximum
      degradation efficiency. The optimum values of solution pH, dye concentration, and
      photocatalyst dosage were 11, 10 ppm, and 75 mg L(-1), respectively. 

PMID- 25985021
TI  - Sulphuric ether as "salvation oil": a 2% solution "in place of a physician".

PMID- 25985019
TI  - Common Oncogene Mutations and Novel SND1-BRAF Transcript Fusion in Lung
      Adenocarcinoma from Never Smokers.
AB  - Lung adenocarcinomas from never smokers account for approximately 15 to 20% of
      all lung cancers and these tumors often carry genetic alterations that are
      responsive to targeted therapy. Here we examined mutation status in 10 oncogenes
      among 89 lung adenocarcinomas from never smokers. We also screened for oncogene
      fusion transcripts in 20 of the 89 tumors by RNA-Seq. In total, 62 tumors had
      mutations in at least one of the 10 oncogenes, including EGFR (49 cases, 55%), K
      ras (5 cases, 6%), BRAF (4 cases, 5%), PIK3CA (3 cases, 3%), and ERBB2 (4 cases,
      5%). In addition to ALK fusions identified by IHC/FISH in four cases, two
      previously known fusions involving EZR- ROS1 and KIF5B-RET were identified by RNA
      Seq as well as a third novel fusion transcript that was formed between exons 1-9
      of SND1 and exons 2 to 3' end of BRAF. This in-frame fusion was observed in 3/89
      tested tumors and 2/64 additional never smoker lung adenocarcinoma samples.
      Ectopic expression of SND1-BRAF in H1299 cells increased phosphorylation levels
      of MEK/ERK, cell proliferation, and spheroid formation compared to parental mock
      transfected control. Jointly, our results suggest a potential role of the novel
      BRAF fusion in lung cancer development and therapy. 

PMID- 25985022
TI  - "Pure nitrous oxide" advertised by F. D. Davis, D.D.S.

PMID- 25985023
TI  - John Bonica's Presentation Copy to Capt. Thomas Robbins.

PMID- 25985025
TI  - Practice improvements based on participation in simulation for the maintenance of
      certification in anesthesiology program.
AB  - BACKGROUND: This study describes anesthesiologists' practice improvements
      undertaken during the first 3 yr of simulation activities for the Maintenance of
      Certification in Anesthesiology Program. METHODS: A stratified sampling of 3 yr
      (2010-2012) of participants' practice improvement plans was coded, categorized,
      and analyzed. RESULTS: Using the sampling scheme, 634 of 1,275 participants in
      Maintenance of Certification in Anesthesiology Program simulation courses were
      evaluated from the following practice settings: 41% (262) academic, 54% (339)
      community, and 5% (33) military/other. A total of 1,982 plans were analyzed for
      completion, target audience, and topic. On follow-up, 79% (1,558) were fully
      completed, 16% (310) were partially completed, and 6% (114) were not completed
      within the 90-day reporting period. Plans targeted the reporting individual (89%
      of plans) and others (78% of plans): anesthesia providers (50%), non-anesthesia
      physicians (16%), and non-anesthesia non-physician providers (26%). From the
      plans, 2,453 improvements were categorized as work environment or systems changes
      (33% of improvements), teamwork skills (30%), personal knowledge (29%), handoff
      (4%), procedural skills (3%), or patient communication (1%). The median word
      count was 63 (interquartile range, 30 to 126) for each participant's combined
      plans and 147 (interquartile range, 52 to 257) for improvement follow-up reports.
      CONCLUSIONS: After making a commitment to change, 94% of anesthesiologists
      participating in a Maintenance of Certification in Anesthesiology Program
      simulation course successfully implemented some or all of their planned practice
      improvements. This compares favorably to rates in other studies. Simulation
      experiences stimulate active learning and motivate personal and collaborative
      practice improvement changes. Further evaluation will assess the impact of the
      improvements and further refine the program.

PMID- 25985026
TI  - Is permissive hypercarbia pneumoprotective?

PMID- 25985027
TI  - In reply.

PMID- 25985024
TI  - Genetic and Clinical Factors Associated with Chronic Postsurgical Pain after
      Hernia Repair, Hysterectomy, and Thoracotomy: A Two-year Multicenter Cohort
      Study.
AB  - BACKGROUND: Chronic postsurgical pain (CPSP) has been linked to many surgical
      settings. The authors aimed to analyze functional genetic polymorphisms and
      clinical factors that might identify CPSP risk after inguinal hernia repair,
      hysterectomy, and thoracotomy. METHODS: This prospective multicenter cohort study
      enrolled 2,929 patients scheduled for inguinal hernia repair, hysterectomy
      (vaginal or abdominal), or thoracotomy. The main outcome was the incidence of
      CPSP confirmed by physical examination 4 months after surgery. The secondary
      outcome was CPSP incidences at 12 and 24 months. The authors also tested the
      associations between CPSP and 90 genetic markers plus a series of clinical
      factors and built a CPSP risk model. RESULTS: Within a median of 4.4 months, CPSP
      had developed in 527 patients (18.0%), in 13.6% after hernia repair, 11.8% after
      vaginal hysterectomy, 25.1% after abdominal hysterectomy, and 37.6% after
      thoracotomy. CPSP persisted after a median of 14.6 months and 26.3 months in 6.2%
      and 4.1%, respectively, after hernia repair, 4.1% and 2.2% after vaginal
      hysterectomy, 9.9% and 6.7% after abdominal hysterectomy, and 19.1% and 13.2%
      after thoracotomy. No significant genetic differences between cases and controls
      were identified. The risk model included six clinical predictors: (1) surgical
      procedure, (2) age, (3) physical health (Short Form Health Survey-12), (4) mental
      health (Short Form Health Survey-12), (5) preoperative pain in the surgical
      field, and (6) preoperative pain in another area. Discrimination was moderate (c
      statistic, 0.731; 95% CI, 0.705 to 0.755). CONCLUSIONS: Until unequivocal genetic
      predictors of CPSP are understood, the authors encourage systematic use of
      clinical factors for predicting and managing CPSP risk.

PMID- 25985029
TI  - In reply.

PMID- 25985028
TI  - Technique and time range used for early detection of inflammation after
      volutrauma.

PMID- 25985035
TI  - Seeing Analgesia during General Anesthesia: Three Ways.

PMID- 25985036
TI  - Nicotine promotes Streptococcus mutans extracellular polysaccharide synthesis,
      cell aggregation and overall lactate dehydrogenase activity.
AB  - Several epidemiology studies have reported a positive relationship between
      smoking and dental caries. Nicotine, an alkaloid component of tobacco, has been
      demonstrated to stimulate biofilm formation and metabolic activity of
      Streptococcus mutans, one of the most important pathogens of dental caries. The
      first aim of the present study was to explore the possible mechanisms leading to
      increased biofilm by nicotine treatment from three aspects, extracellular
      polysaccharides (EPS) synthesis, glucosyltransferase (Gtf) synthesis and glucan
      binding protein (Gbp) synthesis at the mRNA and protein levels. The second aim
      was to investigate how nicotine affects S. mutans virulence, particular in
      lactate dehydrogenase (LDH) activity. Confocal laser scanning microscopy results
      demonstrated that both biofilm bacterial cell numbers and EPS were increased by
      nicotine. Gtf and GbpA protein expression of S. mutans planktonic cells were
      upregulated while GbpB protein expression of biofilm cells were downregulated by
      nicotine. The mRNA expression trends of those genes were mostly consistent with
      results on protein level but not statistically significant, and gtfD and gbpD of
      biofilm cells were inhibited. Nicotine was not directly involved in S. mutans LDH
      activity. However, since it increases the total number of bacterial cells in
      biofilm, the overall LDH activity of S. mutans biofilm is increased. In
      conclusion, nicotine stimulates S. mutans planktonic cell Gtf and Gbp expression.
      This leads to more planktonic cells attaching to the dental biofilm. Increased
      cell numbers within biofilm results in higher overall LDH activity. This
      contributes to caries development in smokers.

PMID- 25985037
TI  - Can insoluble polysaccharide concentration in dental plaque, sugar exposure and
      cariogenic microorganisms predict early childhood caries? A follow-up study.
AB  - BACKGROUND: Insoluble polysaccharide (IP) has been associated with caries
      prevalence in young children. However, the power of IP to predict ECC needs to be
      demonstrated. AIMS: To assess the relationships between early childhood caries
      (ECC) and extracellular insoluble polysaccharides (IP) in dental plaque, sugar
      exposure and cariogenic microorganisms. DESIGN: Visible plaque on maxillary
      incisors was recorded, followed by caries diagnosis in 65 preschoolers (3-4
      years) at baseline and after 1 year. Plaque was collected for mutans streptococci
      (MS), total microorganism (TM) and lactobacilli (LB) enumerations in selective
      media, as well as for IP analysis, which was later assessed by colorimetry.
      Sugar/sucrose exposure was assessed by a diet chart. RESULTS: Positive
      correlations were found among the prevalence of caries and MS, TM, LB, solid
      sucrose and visible dental plaque. Additionally, children with IP concentrations
      in dental plaque higher than 2.36 MUg/mg (odds ratio-OR=6.8), with visible plaque
      on maxillary incisors (OR=4.3), harbouring LB (OR=13) and exposed to solid sugar
      more than twice/day (OR=5) showed higher risk of developing caries (p<0.05).
      CONCLUSION: Extracellular insoluble polysaccharides, solid sugar/sucrose, visible
      dental plaque and cariogenic microorganisms could predict caries development,
      partially explaining the ECC pattern.

PMID- 25985038
TI  - Effects of the iontophoresis of lignocaine with epinephrine into exposed dentine
      on the sensitivity of the dentine in man.
AB  - OBJECTIVE: To determine the effects of the iontophoretic application of
      lignocaine and epinephrine to exposed dentine on the sensitivity of the dentine
      in human subjects. DESIGN: The experiments were carried out on 13 healthy
      premolars (13 subjects) that were scheduled for extraction. Dentine was exposed
      at the tip of the buccal cusp by cutting a cavity which was etched with 35%
      phosphoric acid. The sensitivity of the dentine was tested with probing and air
      blast stimuli. The subject indicated the intensity of any pain produced with a
      score of 0-100. In 7 teeth, the cavity was filled with a solution containing 20%
      (w/v) lignocaine HCl and 0.1% (w/v) epinephrine HCl, and an iontophoretic current
      of 120 MUA was passed for 90s. The sensitivity of the dentine was tested before
      and immediately after the treatment and then at 10 min. intervals for 40 min.
      Pulpal blood flow was recorded at each stage. Control experiments were carried
      out on 6 teeth using a solution containing only the epinephrine. RESULTS: The
      lignocaine plus epinephrine solution completely blocked the pain produced by both
      forms of stimulus immediately, and this continued for at least 40 min. It also
      produced an immediate fall in pulpal blood flow that also lasted for at least 40
      min. The epinephrine solution had the same effect on pulpal blood flow but no
      effect on dentine sensitivity. CONCLUSIONS: The topical application of 20%
      lignocaine and 0.1% epinephrine, with an iontophoretic current of 120MUA for 90s,
      will anaesthetize exposed, normal, dentine.

PMID- 25985040
TI  - Mechanical manipulations on electronic transport of graphene nanoribbons.
AB  - We study the effects of uniaxial strains on the transport properties of graphene
      nanoribbons (GNRs) connected with two metallic leads in heterojunctions, using
      the transfer matrix method. Two typical GNRs with zigzag and armchair boundaries
      are considered and the tension is applied either parallel or perpendicular to the
      ribbon axis. It turns out that the electron-hole symmetry is missing in the gate
      voltage dependence of the conductance data of the armchair GNRs, while it
      persists in the zigzag ribbons under any strains. For an armchair GNR with a
      vertical tension applied, a sharp drop of conductance is found near the critical
      value of the strain inducing a quantum phase transition, which allows one to
      determine the critical strain accurately via measuring the conductance. In the
      zigzag ribbon, there exists a range of gate voltage around zero, where the
      conductance is insensitive to the small horizontal strains. The band structures
      and low-energy properties are calculated to elucidate the mechanism on the strain
      effects in GNRs. We expect that our results can be useful in developing graphene
      based strain sensors. 

PMID- 25985039
TI  - The iontophoresis of lignocaine with epinephrine into carious dentine for pain
      control during cavity preparation in human molars.
AB  - OBJECTIVE: To determine the effectiveness of the iontophoretic delivery of
      lignocaine with epinephrine through carious dentine for pain control during
      cavity preparation. DESIGN: The experiments were carried out on 56 carious molars
      that required class I restorations in 42 subjects (aged 15-20 years). The
      overhanging enamel and soft caries were removed then the sensitivity of the
      exposed dentine was tested with drilling, probing and air blast stimuli. The
      subject indicated the intensity of any pain produced by marking a visual analogue
      scale (VAS). The cavity was then filled with 20% w/v lidocaine with 0.1% w/v
      epinephrine and a 200 MUA iontophoretic current applied for 2 min after which the
      sensitivity of the dentine was re-tested. If the dentine was not anaesthetized,
      the treatment and testing were repeated up to 6 times. RESULTS: The total
      duration (min) of iontophoresis required to anaesthetize the dentine was: 2 in 7
      teeth, 4 in 17 teeth, 6 in 14 teeth, 8 in 4 teeth, and 10 in 7 teeth. The
      remaining 7 teeth were not anaesthetized even after 14 min of iontophoresis.
      CONCLUSIONS: The iontophoretic delivery of lignocaine with epinephrine
      anaesthetized dentine for cavity preparation in 49 of 56 (87.5%) of carious
      molars.

PMID- 25985041
TI  - Supervisory processes in the training of psychotherapists: Introduction to the
      special section.
AB  - To help advance the dialogue on effective supervisory processes, we are proud to
      introduce this special section on supervisory processes. This special section
      follows the same format of the Clinical Processes published in Psychotherapy.
      Specifically, authors were charged to describe two to three supervisory actions
      that are important for an effective supervisory session. For each supervisory
      process, each author provided information on each of the following areas: (a) the
      theoretical basis for this action and how students are expected to gain new
      knowledge, skills, or/and awareness, (b) two to three verbatim supervisory
      exchanges clearly demonstrating this action, and (c) any supervisory or research
      that supports the use of this action.

PMID- 25985042
TI  - Evidence-based supervision: Tracking outcome and teaching principles of change in
      clinical supervision to bring science to integrative practice.
AB  - Supervision is the primary way in which psychotherapy trainees develop the skills
      of applying interventions, conceptualizing cases, and practicing self-reflection.
      Although critical to professional development, the nature and objectives of
      supervision can vary widely among supervisors, depending on idiosyncratic
      differences and the orientation used. As clinical psychology moves toward
      integrating science and practice, the need to teach students evidence-based
      principles of therapeutic change and how to use outcome measures to enhance
      progress is paramount. Furthermore, with hundreds of "evidence-based"
      interventions and widely diverse supervisors, the fact that cross-cutting
      interventions and common factors carry the burden of most therapeutic change is
      frequently lost. In this article, we outline an experimental training system that
      is being tested as a means to teach student-therapists to use empirically
      established moderators (treatment factors) and mediators of change to tailor
      their interventions to client differences. This experimental approach is derived
      from Systematic Treatment Selection (Beutler, Clarkin, & Bongar, 2000), a cross
      cutting system that can be used to aid individualized treatment planning as well
      as to track and use client outcomes in clinical supervision within a graduate
      level training clinic.

PMID- 25985043
TI  - Group as social microcosm: Within-group interpersonal style is congruent with
      outside group relational tendencies.
AB  - The notion that individuals' interpersonal behaviors in the context of therapy
      reflects their interpersonal behaviors outside of therapy is a fundamental
      hypothesis underlying numerous systems of psychotherapy. The social microcosm
      hypothesis, in particular, claims the interpersonal therapy group becomes a
      reflection of group members' general tendencies, and can thus be used as
      information about members' interpersonal functioning as well as an opportunity
      for learning and behavior change. The current study tested this hypothesis using
      data drawn from 207 individuals participating in 22 interpersonal process groups.
      Ratings were made on 2 key interpersonal domains (Dominance and Affiliation) at
      baseline and at Weeks 2, 5, and 8 of the group. Two-level multilevel models (with
      participants nested within groups) were used to account for the hierarchical
      structure, and the social relations model (SRM; Kenny, 1994) was used to estimate
      peer ratings (target effects in SRM) unconfounded with rater bias. Participants
      showed consensus at all time points during the interpersonal process groups on
      one another's levels of dominance and affiliation. In addition, self- and peer
      ratings were stable across time and correlated with one another. Importantly,
      self-ratings made prior to group significantly predicted ratings (self- and peer)
      made within the group, with effect sizes within the medium range. Taken together,
      these results provide robust support for the social microcosm hypothesis and the
      conjecture that interpersonal style within-group therapy is reflective of broader
      interpersonal tendencies.

PMID- 25985044
TI  - Psychodynamic/interpersonal group psychotherapy for perfectionism: Evaluating the
      effectiveness of a short-term treatment.
AB  - This study sought to determine whether clinically significant improvement could
      be obtained using a psychodynamic/interpersonal group treatment based on a
      comprehensive conceptualization of perfectionism. A sample of 71 community
      recruited perfectionistic individuals participated in the University of British
      Columbia Perfectionism Treatment Study. Eighteen of these participants were
      initially nonrandomly assigned to a waitlist control condition. All participants
      completed measures of perfectionism traits, perfectionistic self-presentation,
      and automatic perfectionistic thoughts, as well as measures of distress including
      depression, anxiety, and interpersonal problems at pretreatment, posttreatment,
      and at a 4-month follow-up. Multilevel modeling demonstrated that perfectionism
      levels decreased with large effect sizes and that these decreases were associated
      with reductions in distress measures. Clinically significant decreases were found
      in all perfectionism components, and posttreatment scores on most variables were
      significantly lower in the treatment condition versus the waitlist control
      condition. The findings suggest that psychodynamic/interpersonal group treatment
      is effective in treating components of perfectionism.

PMID- 25985045
TI  - Client attachment and therapist feelings in the treatment of bulimia nervosa.
AB  - The relationship between client attachment and therapist postsession feelings was
      investigated in a randomized clinical trial of psychoanalytic psychotherapy (PPT)
      and cognitive behavior therapy (CBT) for bulimia nervosa. Therapists completed
      feeling word checklists after each session, and client attachment was assessed
      with the Adult Attachment Interview. A factor analysis identified 3 feeling
      factors, Happy/Enthusiastic, Overwhelmed/Moved, and Indifferent/Bored. Positive
      feelings were predominant, but PPT therapists reported more negative and fewer
      positive feelings than CBT therapists did. Client improvement in terms of
      frequency of bulimic episodes and general psychiatric distress was related to an
      increase in Happy/Enthusiastic feelings. Multilevel analyses indicated
      significant interactions between therapy type and client dismissing versus
      preoccupied attachment in predicting therapist negative emotional reactions. PPT
      therapist felt more Indifferent/Bored the more dismissing clients were, whereas
      CBT therapists felt more Overwhelmed/Moved the more preoccupied clients were.

PMID- 25985047
TI  - A case study in treating chronic comorbid obsessive-compulsive disorder and
      depression with behavioral activation and pharmacotherapy.
AB  - Obsessive-compulsive disorder (OCD) is difficult to treat, and more so when
      comorbid with major depressive disorder (MDD). The aim of the present case study
      was to examine effects of behavioral activation (BA) and pharmacotherapy with an
      adult with chronic comorbid OCD and MDD. BA aimed at increasing approach
      behaviors in life activities and decreasing avoidant and inactive behaviors.
      After 21 months of treatment at a community mental health clinic, OCD and MDD
      symptoms, including compulsive checking behaviors, were no longer at clinical
      levels. Symptom alleviation and psychological health improved in line with
      increases in activities of living such as self-care, domestic, social, and
      studying, and decreases in medications from a regimen of mood stabilizers and
      anxiolytics to a sole antidepressant. The participant was satisfied with
      treatment procedures and outcome. The results add to growing evidence of
      effective BA treatments for comorbid disorders that include depression.

PMID- 25985046
TI  - Predictors of longitudinal outcomes after unstable response to acute-phase
      cognitive therapy for major depressive disorder.
AB  - After patients with major depressive disorder (MDD) respond to acute-phase
      cognitive therapy (CT), continuation-phase treatments may be applied to improve
      long-term outcomes. We clarified which CT responders experience remission,
      recovery, relapse, and recurrence by testing baseline demographic, clinical, and
      personality variables. The sample of CT responders at higher risk of relapse (N =
      241) was randomized to 8 months of continuation-phase CT, double-blinded
      fluoxetine, or pill placebo, and followed 24 months (Jarrett & Thase, 2010).
      Patients with lower positive emotionality and behavioral activation at the end of
      acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition,
      patients with lower positive emotionality and behavioral activation, as well as
      higher residual depression (including emotional, cognitive, and social facets),
      showed decreased probability of remission (>=6 continuous weeks of minimal or
      absent symptoms) after acute-phase CT. Finally, patients with greater residual
      depression, as well as younger age and earlier MDD onset, showed decreased
      probability of recovery (>=35 continuous weeks of minimal or absent symptoms)
      after acute-phase CT. Moderator analyses did not reveal differential prediction
      across the continuation phase treatment arms. These results may help clinicians
      gauge the prognoses and need for continuation treatment among MDD patients who
      respond to acute-phase CT.

PMID- 25985048
TI  - Coherent fusion of water array and protonated amine in a metal-sulfate-based
      coordination polymer for proton conduction.
AB  - A new function of metal-sulfate-based coordination polymer (CP) for proton
      conduction was investigated through rational integration of a continuous water
      array and protonated amine in the coordination space of the CP. The H-bonded
      arrays of water molecules along with nitrogen-rich aromatic cation (protonated
      melamine) facilitate proton conduction in the compound under humid conditions.
      Although several reports of metal-oxalate/phosphate-based CPs showing proton
      conduction are known, this is the first designed synthesis of a metal-sulfate
      based CP bearing water arrays functioning as a solid-state proton conductor. 

PMID- 25985049
TI  - Ergonomic design and evaluation of new surgical scissors.
AB  - The purpose of this study is to design a new surgical scissors handle and
      determine its effectiveness with various usability indices. A new scissors handle
      was designed that retains the professional grip but has the shapes of the eye
      rings modified to fit the thumb and ring finger and finger rests for the index
      and little finger. The newly designed scissors and traditional scissors were
      compared by electromyography, subjective evaluation and task performance in
      experiments using cutting and peeling tasks. The newly designed scissors reduced
      muscle load in both hand during cutting by the closing action, and reduced the
      muscle load in the left hand during peeling by the opening action through active
      use of the right hand. In evaluation by surgeons, task performance improved in
      addition to the decrease in muscle load. The newly designed scissors used in this
      study demonstrated high usability. PRACTITIONER SUMMARY: A new scissors handle
      was designed that has the eye rings modified to fit the thumb and ring finger.
      The newly designed scissors reduced muscle load and enabled active use of the
      right hand. In evaluation by surgeons, task performance improved in addition to
      the decrease in muscle load.

PMID- 25985050
TI  - Mode pattern of internal flow in a water droplet on a vibrating hydrophobic
      surface.
AB  - The objective of this study is to understand the mode pattern of the internal
      flow in a water droplet placed on a hydrophobic surface that periodically and
      vertically vibrates. As a result, a water droplet on a vibrating hydrophobic
      surface has a typical shape that depends on each resonance mode, and,
      additionally, we observed a diversified lobe size and internal flows in the water
      droplet. The size of each lobe at the resonance frequency was relatively greater
      than that at the neighboring frequencies, and the internal flow of the nth order
      mode was also observed in the flow visualization. In general, large symmetrical
      flow streams were generated along the vertical axis in each mode, with a large
      circulating movement from the bottom to the top, and then to the triple contact
      line along the droplet surface. In contrast, modes 2 and 4 generated a Y-shaped
      flow pattern, in which the flow moved to the node point in the lower part of the
      droplet, but modes 6 and 8 had similar patterns, with only a little difference.
      In addition, as a result of the PIV measurement, while the flow velocity of mode
      4 was faster than that of model 2, those of modes 6 and 8 were almost similar. 

PMID- 25985051
TI  - Clinical comorbidity predictive measures in ex vivo T-cell-depleted allogeneic
      hematopoietic stem cell transplantation.

PMID- 25985052
TI  - Tobacco smoking is associated with infectious pulmonary complications after
      allogeneic hematopoietic stem cell transplantation.

PMID- 25985054
TI  - Effect of Plant Growth Regulators on Phytoremediation of Hexachlorocyclohexane
      Contaminated Soil.
AB  - The influence of three plant growth regulators, indolebutyric acid (IBA),
      thidiazuron (TDZ) and gibberellic acid (GA3), either individually or in pair-wise
      combinations, on the ability of waxy corn plant to remove hexachlorocyclohexane
      (HCH) from contaminated soil was studied. Waxy corn seeds were immersed for 3 h
      in solutions of 1.0 mg/l IBA, 0.01 mg/l TDZ, 0.1 mg/l GA3, or a mixture of two of
      the growth regulators, and then inoculated in soil contaminated with 46.8 mg/kg
      HCH for 30 days. Pretreatment of corn seeds with the plant growth regulators did
      not enhance corn growth when compared with those immersed in distilled water
      (control), but the pretreatment enhanced HCH removal significantly. On day 30,
      HCH concentration in the bulk soil planted with corn seeds pretreated with GA3 or
      TDZ+GA3 decreased by 97.4% and 98.4%, respectively. In comparison, HCH removal in
      soil planted with non-pretreated control waxy corn seeds was only 35.7%. The
      effect of several growth regulator application methods was tested with 0.01 mg/l
      TDZ. The results showed that none of the methods, which ranged from seed
      immersion, watering in soil, or spraying on shoots, affected HCH removal from
      soil. However, the method of applying the growth regulators may affect corn
      growth. Watering the corn plant with TDZ in soil led to higher root fresh weight
      (2.2 g) and higher root dried weight (0.57 g) than the other treatments (0.2-1.7
      g root fresh weight and 0.02-0.43 g root dried weight) on day 30. Varying the
      concentrations of GA3 did not affect the enhancement of corn growth and HCH
      removal on day 30. The results showed that plant growth regulators may have
      potential for use to enhance HCH phytoremediation.

PMID- 25985055
TI  - A Novel Nanomaterial of Graphene Oxide Dotted with Ni Nanoparticles Produced by
      Supercritical CO2-Assisted Deposition for Reducing Friction and Wear.
AB  - Graphene oxide dotted with nickel nanoparticles (Sc-Ni/GO) was synthesized by
      chemical deposition with the assistance of supercritical carbon dioxide (scCO2).
      The deposited Ni nanoparticles with diameters less than 5 nm are uniformly
      anchored on the surfaces of GO nanosheets. The as-prepared Sc-Ni/GO composites
      were employed as lubricating additives in paraffin oil and their tribological
      properties were tested using a four-ball tribometer. The results demonstrate that
      the Sc-Ni/GO composites are efficient lubricant additives. Adding 0.08 wt % Sc
      Ni/GO into paraffin oil can reduce the friction coefficient and wear scar
      diameter by 32 and 42%, respectively, in comparison with the pure oil. In
      addition, Sc-Ni/GO composites exhibit superior lubricating performances than nano
      Ni, GO nanosheets, and Ni/GO composites produced without the aid of scCO2. Such
      excellent lubricating properties of the Sc-Ni/GO composites derive from the
      synergistic lubricating actions of Ni nanoparticles and GO nanosheets during the
      rubbing process. The synergistic lubricating actions are closely related to the
      microstructure of the nanocomposites and the characteristic features of transfer
      film formed on the contact steel balls. The anchored Ni nanoparticles with
      smaller size and more uniform distribution on GO surfaces and the thin transfer
      film formed on the contact balls favor the full play of the synergistic actions. 

PMID- 25985056
TI  - Predicting propulsive forces using distributed sensors in a compliant, high DOF,
      robotic fin.
AB  - Engineered robotic fins have adapted principles of propulsion from bony-finned
      fish, using spatially-varying compliance and complex kinematics to produce and
      control the fin's propulsive force through time. While methods of force
      production are well understood, few models exist to predict the propulsive forces
      of a compliant, high degree of freedom, robotic fin as it moves through fluid.
      Inspired by evidence that the bluegill sunfish (Lepomis macrochirus) has bending
      sensation in its pectoral fins, the objective of this study is to understand how
      sensors distributed within a compliant robotic fin can be used to estimate and
      predict the fin's propulsive force. A biorobotic model of a bluegill sunfish
      pectoral fin was instrumented with pressure and bending sensors at multiple
      locations. Experiments with the robotic fin were executed that varied the
      swimming gait, flapping frequency, stroke phase, and fin stiffness to understand
      the forces and sensory measures that occur during swimming. A convolution-based,
      multi-input-single-output (MISO) model was selected to model and study the
      relationships between sensory data and propulsive force. Subsets of sensory data
      were studied to determine which sensor modalities and sensor placement locations
      resulted in the best force predictions. The propulsive forces of the fin were
      accurately predicted using the linear MISO model on intrinsic sensory data.
      Bending sensation was more effective than pressure sensation for predicting
      propulsive forces, and the importance of bending sensation was consistent with
      several results in biology and engineering studies. It was important to have a
      spatial distribution of sensors and multiple sensory modalities in order to
      predict forces across large changes to dynamics. The relationship between
      propulsive forces and intrinsic sensory measures is complex, and good models
      should allow for temporal lags between forces and sensory data, changes to the
      model within a fin stroke, and changes to the model through gait transitions. 

PMID- 25985057
TI  - Completely Digital Two-Visit Immediately Loaded Implants: Proof of Concept.
AB  - Implant dentistry has become a common treatment alternative, yet only a small
      percentage of patients missing teeth are receiving its benefits. Significant
      limitations are the small percent of practitioners placing implants due to the
      long learning curve, as well as the time commitment on the part of the patient.
      This proof of concept demonstrates clinical implant treatment requiring years of
      manual skill development on the part of the surgeon, restorative dentist, and
      technician can be accomplished in 2 visits, completely digitally, without the
      need for conventional impressions, laboratory procedures, and advanced manual
      skills. This technique results in reduced learning curve and treatment time. The
      first visit consists of consultation, diagnosis, CT and optical surface scans of
      the implant site to include: soft tissue, adjacent teeth, and opposing arch. This
      digital information is imported and interactively reconstructed in a 3-D open
      format implant planning software. The implant and restoration are now precisely
      planned into the optimal bone position with the ideal emergence profile for
      biologically and esthetically designed restoration. This information is then
      electronically forwarded to a production facility, where all necessary models are
      digitally printed and the immediate crown is digitally milled. On the second
      visit, the patient returns for guided implant insertion and immediate
      restoration. As digital procedures are refined, many more dental professionals
      will become involved in providing implant therapy earlier in their careers. This
      promises to result in reduced costs, making implants available to millions more
      patients who could benefit from them. 

PMID- 25985053
TI  - Pushing the envelope-nonmyeloablative and reduced intensity preparative regimens
      for allogeneic hematopoietic transplantation.
AB  - Allogeneic hematopoietic cell transplantation (HCT) was originally developed to
      allow delivery of myeloablative doses of chemotherapy and radiotherapy. With
      better understanding of disease pathophysiology, the graft vs malignancy (GVM)
      effect of allogeneic hematopoietic transplantation and toxicities associated with
      myeloablative conditioning (MAC) regimens, the focus shifted to developing less
      toxic conditioning regimens to reduce treatment-related morbidity without
      compromising survival. Although HCT with MAC is preferred to reduced intensity
      conditioning (RIC) for most patients ?60 years with AML/myelodysplastic syndrome
      and ALL, RIC and nonmyeloablative (NMA) regimens allow HCT for many otherwise
      ineligible patients. Reduced intensity preparative regimens have produced high
      rates of PFS for diagnoses, which are highly sensitive to GVM. Relapse of the
      malignancy is the major cause of treatment failure with RIC/NMA HCT.
      Incorporation of novel agents like bortezomib or lenalidomide, addition of
      cellular immunotherapy and use of targeted radiation therapies could further
      improve outcome. In this review, we discuss commonly used RIC/NMA regimens and
      promising novel regimens. 

PMID- 25985058
TI  - Large Thermal Conductivity Differences between the Crystalline and Vitrified
      States of DMSO with Applications to Cryopreservation.
AB  - Thermal conductivity of dimethyl-sulfoxide (DMSO) solution is measured in this
      study using a transient hot wire technique, where DMSO is a key ingredient in
      many cryoprotective agent (CPA) cocktails. Characterization of thermal properties
      of cryoprotective agents is essential to the analysis of cryopreservation
      processes, either when evaluating experimental data or for the design of new
      protocols. Also presented are reference measurements of thermal conductivity for
      pure water ice and glycerol. The thermal conductivity measurement setup is
      integrated into the experimentation stage of a scanning cryomacroscope apparatus,
      which facilitates the correlation of measured data with visualization of physical
      events. Thermal conductivity measurements were conducted for a DMSO concentration
      range of 2M and 10M, in a temperature range of -180 degrees C and 25 degrees C.
      Vitrified samples showed decreased thermal conductivity with decreasing
      temperature, while crystalline samples showed increased thermal conductivity with
      decreasing temperature. These different behaviors result in up to a tenfold
      difference in thermal conductivity at -180 degrees C. Such dramatic differences
      can drastically impact heat transfer during cryopreservation and their
      quantification is therefore critical to cryobiology. 

PMID- 25985059
TI  - Morphologic and Molecular Features of Hepatocellular Adenoma with Gadoxetic Acid
      enhanced MR Imaging.
AB  - PURPOSE: To evaluate the diagnostic performance of imaging features of gadoxetic
      acid-enhanced magnetic resonance (MR) imaging to differentiate among
      hepatocellular adenoma (HCA) subtypes by using the histopathologic results of the
      new immunophenotype and genotype classification and to correlate the enhancement
      pattern on the hepatobiliary phase (HBP) with the degrees of expression of
      organic anion transporting polypeptide (OATP1B1/3), multidrug resistance
      associated protein 2 (MRP) (MRP2), and MRP 3 (MRP3) transporters. MATERIALS AND
      METHODS: This retrospective study was approved by the institutional review board,
      and the requirement for informed consent waived. MR imaging findings of 29
      patients with 43 HCAs were assessed by two radiologists independently then
      compared with the histopathologic analysis as the standard of reference. Receiver
      operating characteristic curves and Spearman rank correlation coefficient were
      used to test the diagnostic performance of gadoxetic acid-enhanced MR imaging
      features, which included the retention or washout at HBP and degree of
      transporter expression. Interreader agreement was assessed by using the kappa
      statistic with 95% confidence interval. RESULTS: The area under the curve for the
      diagnosis of inflammatory HCA was 0.79 (95% confidence interval: 0.64, 0.90); for
      the steatotic type, it was 0.90 (95% confidence interval: 0.77, 0.97); and for
      the beta-catenin type, it was 0.87 (95% confidence interval: 0.74, 0.95). There
      were no imaging features that showed a significant statistical correlation for
      the diagnosis of unclassified HCAs. On immunohistochemical staining, OATP1B1/3
      expression was the main determinant for the retention, whereas MRP3 was the key
      determinant for washout of gadoxetic acid at HBP (P < .001). MRP2 appeared to
      have no role. CONCLUSION: Gadoxetic acid-enhanced MR imaging features may suggest
      the subtype of HCA. The degree of OATP1B1/3 and MRP3 expression correlated
      statistically with gadoxetic acid retention and washout, respectively, in the
      HBP.

PMID- 25985060
TI  - The High Performance of Crystal Water Containing Manganese Birnessite Cathodes
      for Magnesium Batteries.
AB  - Rechargeable magnesium batteries have lately received great attention for large
      scale energy storage systems due to their high volumetric capacities, low
      materials cost, and safe characteristic. However, the bivalency of Mg(2+) ions
      has made it challenging to find cathode materials operating at high voltages with
      decent (de)intercalation kinetics. In an effort to overcome this challenge, we
      adopt an unconventional approach of engaging crystal water in the layered
      structure of Birnessite MnO2 because the crystal water can effectively screen
      electrostatic interactions between Mg(2+) ions and the host anions. The crucial
      role of the crystal water was revealed by directly visualizing its presence and
      dynamic rearrangement using scanning transmission electron microscopy (STEM).
      Moreover, the importance of lowering desolvation energy penalty at the cathode
      electrolyte interface was elucidated by working with water containing nonaqueous
      electrolytes. In aqueous electrolytes, the decreased interfacial energy penalty
      by hydration of Mg(2+) allows Birnessite MnO2 to achieve a large reversible
      capacity (231.1 mAh g(-1)) at high operating voltage (2.8 V vs Mg/Mg(2+)) with
      excellent cycle life (62.5% retention after 10000 cycles), unveiling the
      importance of effective charge shielding in the host and facile Mg(2+) ions
      transfer through the cathode's interface. 

PMID- 25985061
TI  - Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for
      Adolescents: A Generation at Stake.

PMID- 25985062
TI  - Utility of the Japanese version of the 9-item Wearing-off Questionnaire.
AB  - BACKGROUND AND PURPOSE: The 9-item Wearing-off Questionnaire (WOQ-9) is a useful
      tool for screening of wearing-off. We performed a validation study of the
      Japanese version of the WOQ-9 (JWOQ-9) using a cross-sectional design in Japanese
      Parkinson's disease (PD) patients diagnosed with sporadic PD and treated with
      levodopa. METHODS: Subjects with severe dementia, uncontrolled psychiatric
      comorbidities, and previous PD neurosurgery were excluded. The wearing-off
      phenomenon was detected according to the JWOQ-9, and the results were compared
      with independent evaluations of wearing-off conducted by PD specialists blinded
      to the JWOQ-9 results. To validate the JWOQ-9, a sample size of at least 70
      patients with wearing-off and 70 patients without wearing-off was required.
      Therefore, a total of 180 patients (101 patients with wearing-off and 79 patients
      without wearing-off) were enrolled. RESULTS: The sensitivity, specificity,
      positive predictive value, and negative predictive value of the JWOQ-9 were
      94.1%, 39.2%, 66.4%, and 83.8%, respectively. Motor symptom questions
      demonstrated both moderate sensitivity (58.1-87.3%) and specificity (60.4-87.5%).
      In contrast, non-motor symptom questions demonstrated fair to moderate
      sensitivity (51.5-64.6%), with high specificity (80.0-94.1%). Like the original
      WOQ-9, the JWOQ-9 exhibits significant value for detecting possible wearing-off.
      CONCLUSIONS: The JWOQ-9 is a useful screening tool for detecting wearing-off of
      both motor and non-motor symptoms.

PMID- 25985063
TI  - Proteomic analysis of three gonad types of swamp eel reveals genes differentially
      expressed during sex reversal.
AB  - A variety of mechanisms are engaged in sex determination in vertebrates. The
      teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for
      vertebrate sexual development. However, the importance of proteome-wide scanning
      for gonad reversal was not previously determined. We report a 2-D electrophoresis
      analysis of three gonad types of proteomes during sex reversal. MS/MS analysis
      revealed a group of differentially expressed proteins during ovary to ovotestis
      to testis transformation. Cbx3 is up-regulated during gonad reversal and is
      likely to have a role in spermatogenesis. Rab37 is down-regulated during the
      reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked
      up in a protein network. These datasets in gonadal proteomes provide a new
      resource for further studies in gonadal development. 

PMID- 25985064
TI  - Anomalous spectral features of a neutral bilayer graphene.
AB  - Graphene and its bilayer are two-dimensional systems predicted to show exciting
      many-body effects near the neutrality point. The ideal tool to investigate
      spectrum reconstruction effects is angle-resolved photoemission spectroscopy
      (ARPES) as it probes directly the band structure with information about both
      energy and momentum. Here we reveal, by studying undoped exfoliated bilayer
      graphene with ARPES, two essential aspects of its many-body physics: the electron
      phonon scattering rate has an anisotropic k-dependence and the type of electronic
      liquid is non-Fermi liquid. The latter behavior is evident from an observed
      electron-electron scattering rate that scales linearly with energy from 100 meV
      to 600 meV and that is associated with the proximity of bilayer graphene to a two
      dimensional quantum critical point of competing orders.

PMID- 25985065
TI  - Dual-probe electrochemical DNA biosensor based on the "Y" junction structure and
      restriction endonuclease assisted cyclic enzymatic amplification for detection of
      double-strand DNA of PML/RARalpha related fusion gene.
AB  - Taking advantage of "Y" junction structure and restriction endonuclease assisted
      cyclic enzymatic amplification, a dual-probe electrochemical DNA (DE-DNA)
      biosensor was designed to detect double-stranded DNA (dsDNA) of acute
      promyelocytic leukemia (APL) related gene. Two groups of detection probes were
      designed, and each group was composed of a biotinylated capture probe and an
      assisted probe. They were separately complementary with two strands of target
      dsDNA in order to prevent the reannealing of the two separate strands from target
      dsDNA. First, thiol functionalized capture probes (C1 and C2) were severally
      assembled onto two different gold electrodes, followed by hybridizing with target
      dsDNA (S1a-S1b) and assistant probes to form two Y-junction-structure ternary
      complexes. Subsequently, restriction sites on the ternary complexes were digested
      by Rsa I, which can release S1a, S1b and biotins from the electrode surfaces.
      Meanwhile, the released S1a and S1b can further hybridize with the unhybridized
      corresponding detection probes and then initiate another new hybridization
      cleavage-separation cycle. Finally, the current signals were produced by the
      enzyme-catalyzed reaction of streptavidin-horse reddish peroxidase (streptavidin
      HRP). The distinct difference in current signals between different sequences
      allowed detection of target dsDNA down to a low detection limit of 47 fM and
      presented excellent specificity with discriminating only a single-base mismatched
      dsDNA sequence. Moreover, this biosensor was also used for assay of polymerase
      chain reaction (PCR) samples with satisfactory results. According to the results,
      the power of the DE-DNA biosensor as a promising tool for the detection of APL
      and other diseases.

PMID- 25985067
TI  - Culturally based substance abuse treatment for American Indians/Alaska Natives
      and Latinos.

PMID- 25985066
TI  - Enantiospecific determination of naftopidil by RRLC-MS/MS reveals stereoselective
      pharmacokinetics and tissue distributions in rats.
AB  - Naftopidil (NAF) is used as a racemate to treat benign prostatic hyperplasia
      (BPH) and to prevent prostate cancer. However, racemic NAF has low
      bioavailability; therefore, it is commonly administered at higher clinical
      dosages compared to other therapeutic BPH drugs. Differences in interactions
      between individual enantiomers and biological macromolecules may result in
      variations in pharmacokinetics and dispositions. This study aimed to investigate
      the pharmacokinetics, bioavailability and tissue distributions of NAF enantiomers
      in rats after intragastric administration of the individual enantiomers. A rapid
      and sensitive liquid chromatography coupled with triple-quadrupole mass
      spectrometric method (RRLC-MS/MS) was developed and validated for determination
      of NAF enantiomers in rat plasma, tissues, urine and feces. After intragastric
      administration, S(-)-NAF in plasma [maximum concentration (C(max)) = 186.4 ng/mL,
      area under the curve from 0 h to 24h (AUC(0-24 h)) = 877.9 ng h/mL] was
      significantly higher than that of R(+)-NAF (C(max) = 133.2 ng/mL, AUC(0-24 h) =
      602.1 ng h/mL). Moreover, S(-)-NAF bioavailability was twice that of R(+)-NAF.
      R(+)-NAF distributions in the prostate, liver, and kidney were significantly
      higher than S(-)-NAF distributions (R/S ratios of 3.16, 1.33, and 2.90,
      respectively). These data reveal the stereoselective pharmacokinetic profiles of
      the two enantiomers in rats.

PMID- 25985068
TI  - Some thoughts about the epidemiology of alcohol and drug use among American
      Indian/Alaska Native populations.
AB  - Researchers have established that rates of alcohol and illicit drug use among
      American Indians/Alaska Natives vary by tribe, gender, and age group, making it
      difficult to get an accurate estimate of the actual extent of the problem of
      substance abuse within this population group. Although percentage rates of
      alcohol consumption are higher in non-Hispanic Whites, American Indians/Alaska
      Natives nevertheless have the highest alcohol-related mortality rates and rates
      of substance use and dependence of all ethnic groups. Alcohol-related motor
      vehicle accidents are especially high for American Indian/Alaska Natives.
      Similarly, illicit drug use is higher among American Indians/Alaska Natives
      across all age groups compared to non-Indians. Data indicate that American
      Indians/Alaska Natives have the highest rates of use for marijuana, cocaine,
      inhalants, hallucinogens, and non-medical use of psychotherapeutics compared to
      other ethnic groups. Anecdotally, use of amphetamine appears to be high within
      some American Indian/Alaska Native tribes and has become a serious concern for
      most American Indian/Alaska Native communities. The percentage of American
      Indian/Alaska Native women using illicit drugs is lower than that found in men,
      except in younger age groups, in which percentage rates of illicit drug use by
      women in some tribes are comparable to rates for men. 

PMID- 25985069
TI  - Epidemiology of substance abuse among Latinos.
AB  - The importance of conducting substance abuse research among ethnic minorities is
      underscored by findings that members of many ethnic minorities in the United
      States report higher rates of heavy drinking and alcohol-related problems than do
      Whites and have increased rates of illicit drug use, abuse, and dependence. It is
      important to better understand ethnic-specific substance use from a public health
      perspective. Recent data suggest that the prevalence of past month alcohol use
      and heavy alcohol use among Hispanics is lower than and the prevalence of binge
      drinking and alcohol abuse or dependence is comparable to that of non-Hispanic
      Whites. These estimates vary among Hispanic subgroups and across gender and age
      groups. The prevalence of past month illicit drug use is also lower among
      Hispanics than that of several other groups, including non-Hispanic Whites. These
      trends are consistent among both men and women, although the prevalence for men
      is nearly twice that of women in nearly all subgroups. Conversely, the prevalence
      of illicit drug abuse or dependence among Hispanics is slightly higher than that
      of non-Hispanic Whites. This article describes national level epidemiological
      data on the prevalence of alcohol and illicit drug use, abuse, and dependence
      among Latinos/Hispanics in the United States in comparison to other race and
      ethnic groups. Previous findings in the literature will be reviewed and new
      analyses using the 2002 National Survey on Drug Use and Health will be presented.
      Given the heterogeneity of Hispanics in the United States, data for Hispanics
      will be broken down by national groups whenever possible. 

PMID- 25985070
TI  - Cultural practices and spiritual development for women in a Native American
      alcohol and drug treatment program.
AB  - The purpose of this study is to develop an instrument that can be used to
      identify clients' readiness for spiritual development and its relationship with
      their participation in American Indian/Alaskan Native practices. Female clients
      and staff from Guiding Star, the female residential substance abuse program at
      Native American Connections in Phoenix, Arizona, participated in the study. Two
      focus groups (8 Native and 5 non-Native clients) were conducted to determine the
      clients' attitudes toward cultural practices. A Native cultural practitioner was
      interviewed regarding the clients' spiritual needs and development. Finally, a
      survey on attitudes toward issues related to spirituality was conducted with 51
      female clients. Readiness for spiritual development was found to be positively
      related to a positive outlook on life, being religious, or participating in
      American Indian/Alaska Native cultural activities. 

PMID- 25985071
TI  - Latino/a Culture and Substance Abuse.
AB  - This article provides descriptions of issues related to Latino/as, alcoholism,
      and substance abuse. A review of the available literature is provided, including
      preliminary data analyses by the National Epidemiologic Survey on Alcoholism and
      Related Conditions conducted by the National Institute on Alcohol Abuse and
      Alcoholism and from the National Hispanic Science Network on Drug Abuse. There is
      some evidence that substance abuse among Hispanics may be increasing, especially
      among adolescents. Despite the dearth of knowledge regarding prevention and
      treatment interventions for Latino/a populations, the evolving evidence-based
      research provides additional information. Some clinical implications are provided
      and directions for research are suggested. 

PMID- 25985072
TI  - Shifting perspectives: culturally responsive interventions with latino substance
      abusers.
AB  - In 2001, there were 35 million Latinos living in the United States. It is
      estimated that by 2050 Latinos will comprise 97 million people in the United
      States, or one-fourth of the U.S. population, establishing this ethnic group as
      the fastest growing and soon to be largest in the country (U.S. Census Bureau,
      2001 ). These numbers highlight the need for a multicultural paradigm shift, or
      the inclusion of culture-specific skills and culturally responsive interventions
      in psychological practice. Latinos face challenges as a racial/ethnic group that
      the traditional Euro-American model of treatment neither addresses nor validates.
      Unfortunately, substance abuse serves a purposeful function for many Latinos as a
      means of escape from the problems related to the social, environmental, and
      political structures. The current article adapts the model set forth by Parham (
      2002 ) as a strength-based therapeutic framework for intervention. The following
      stages are outlined to serve as the basis for most therapeutic encounters with
      clients from all racial and ethnic groups presenting with substance abuse
      problems: therapeutic alliance building, culturally appropriate assessment,
      sociopolitical awareness and liberation, creating collaborative change, and
      addressing sustainability of change. 

PMID- 25985073
TI  - Mexican Americans and historical trauma theory: a theoretical perspective.
AB  - The observed intergenerational stress response to negative social and historical
      events is at the core of historical trauma theory, which has been applied to
      Native Americans, African Americans, and Pacific Islanders, among others. The
      historical and social experiences of the Mexican population living in the United
      States have many parallels that lend themselves to the application of historical
      trauma theory to macro-level and micro-level influences on access to health care,
      physical health status, and mental health status, including substance abuse among
      Mexican Americans. This article highlights the legacy of Spanish colonialism and
      Anglo-American neo-colonialism on Mexicans and Mexican Americans in the
      southwestern United States through a potential application of historical trauma
      theory. 

PMID- 25985074
TI  - Women and substance abuse: gender, age, and cultural considerations.
AB  - Historically, data has shown that a smaller percentage of women use alcohol and
      illicit substances compared to men, and that frequency of use has been lower
      among women compared to use among men. Although this data on usage may be true,
      researchers also acknowledge that substance use among women has been a hidden
      issue, one not realistically acknowledged by society, especially prior to the mid
      1960s. Along with this, more recent data indicates that rates of substance use
      among women are increasing. Factors contributing to this increase in substance
      abuse have begun to receive considerable attention, and recent research suggests
      that many issues exist that are unique to substance use among women. The purpose
      of this article is to discuss gender specific considerations in women's substance
      abuse by examining the history of substance use among women; analyzing gender
      specific factors, including physiological factors, trauma-related factors, mental
      health issues, and cultural considerations that impact on women's substance use;
      articulating treatment approaches for working with substance abusing women and
      girls; and providing recommendations for further research in this area. 

PMID- 25985075
TI  - Connections with nature and environmental behaviors.
AB  - The influence of environmental attitudes on environmental behaviors has long been
      discussed. However, few studies have addressed the foundation of such attitudes.
      In the present study, we explored primitive belief underlying environmental
      attitudes, i.e., connections with nature, and its relationship with pro
      environmental behaviors. Specifically, we used scales, a computerized Implicit
      Association Test, and a situational simulation experiment to examine both
      explicit and implicit connections with nature, both deliberate and spontaneous
      environmental behaviors, and to find correlations between environmental
      connectedness and environmental behaviors. Results showed that explicit
      connectedness was positively correlated with deliberate environmental behaviors,
      while implicit connectedness was positively correlated with spontaneous
      environmental behaviors. Additionally, explicit and implicit connectedness was
      independent of each other. In conclusion, the current study confirms the positive
      role played by connections with nature in promoting environmental behavior, and
      accordingly suggests means to encourage pro-environmental behavior by enhancing
      people's connectedness to nature. 

PMID- 25985076
TI  - Trends in Atomic Parameters for Crystals and Free Ions across the Lanthanide
      Series: The Case of LaCl3:Ln(3+).
AB  - Analyses of the crystal field energy levels of the series LaCl3:Ln(3+) using a
      semiempirical Hamiltonian shows that only five ions (Pr, Nd, Pm, Dy, Ho) meet the
      criteria to avoid overfitting of the atomic part. A new parameter (SNES) has been
      introduced to represent the strength of the normalized electrostatic repulsion
      for these ions. This parameter varies linearly (R(2)adj = 0.9994, N = 5) with the
      reciprocal of the radius of the tripositive lanthanide ion, as expected from the
      form of repulsive Coulomb interaction. The Slater parameters from the crystal
      field analyses, F(k)(corr) (i.e., corrected for the effects of the two-particle
      component of the three-body operator associated with the T(2) parameter), exhibit
      an exponential variation with the number of electrons, n, in 4f(n). This is
      explained by reference to the radial part of a hydrogen-like wave function. The
      ratio of F(k)(corr) with the ab initio free ion Slater parameter F(k)(ab initio)
      varies linearly with n. Fitted parameters F(k)(corr: free ion) from the free ion
      data for Pr(3+) and Nd(3+) show that the corresponding ab initio values are
      between 14 and 27% too high. The spin-orbit coupling constant from crystal field
      analyses (zeta4f) exhibits a quartic variation with atomic number, and the ratio
      zeta4f/zeta4f(ab initio) follows an exponential growth model with n. The results
      serve to confirm the hypothesis that smooth trends can be observed across the
      Ln(3+) series for the fitted parameters despite the fact that the majority of
      experimental data is lacking. 

PMID- 25985077
TI  - Establishment of a Successive Markerless Mutation System in Haemophilus parasuis
      through Natural Transformation.
AB  - Haemophilus parasuis, belonging to the family Pasteurellaceae, is the causative
      agent of Glasser's disease leading to serious economic losses. In this study, a
      successive markerless mutation system for H. parasuis using two sequential steps
      of natural transformation was developed. By the first homologous recombination,
      the target genes were replaced by a cassette carrying kanamycin resistance gene
      and sacB (which confers sensitivity to sucrose) gene using kanamycin selection,
      followed by the second reconstruction to remove the selection cassette, with
      application of sucrose to further screen unmarked mutants. To improve DNA
      transformation frequency, several parameters have been analyzed further in this
      work. With this method, two unmarked deletions in one strain have been generated
      successfully. It is demonstrated that this system can be employed to construct
      multi-gene scarless deletions, which is of great help for developing live
      attenuated vaccines for H. parasuis. 

PMID- 25985079
TI  - Tandem-pulsed acousto-optics: an analytical framework of modulated high-contrast
      speckle patterns.
AB  - Recently we presented acousto-optic (AO) probing of scattering media using
      addition or subtraction of speckle patterns due to tandem nanosecond pulses. Here
      we present a theoretical framework for ideal (polarized, noise-free) speckle
      patterns with unity contrast that links ultrasound-induced optical phase
      modulation, the fraction of light that is tagged by ultrasound, speckle contrast,
      mean square difference of speckle patterns and the contrast of the summation of
      speckle patterns acquired at different ultrasound phases. We derive the important
      relations from basic assumptions and definitions, and then validate them with
      simulations. For ultrasound-generated phase modulation angles below 0.7 rad
      (assuming uniform modulation), we are now able to relate speckle pattern
      statistics to the acousto-optic phase modulation. Hence our theory allows
      quantifying speckle observations in terms of ultrasonically tagged fractions of
      light for near-unity-contrast speckle patterns.

PMID- 25985078
TI  - Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation.
AB  - Hemispheric asymmetry of a wide range of functions is a hallmark of the human
      brain. The visual system has traditionally been thought of as symmetrically
      distributed in the brain, but a growing body of evidence has challenged this
      view. Some highly specific visual tasks have been shown to depend on hemispheric
      specialization. However, the possible lateralization of cerebral responses to a
      simple checkerboard visual stimulation has not been a focus of previous studies.
      To investigate this, we performed two sessions of blood-oxygenation level
      dependent (BOLD) functional magnetic resonance imaging (fMRI) in 54 healthy
      subjects during stimulation with a black and white checkerboard visual stimulus.
      While carefully excluding possible non-physiological causes of left-to-right
      bias, we compared the activation of the left and the right cerebral hemispheres
      and related this to grey matter volume, handedness, age, gender, ocular
      dominance, interocular difference in visual acuity, as well as line-bisection
      performance. We found a general lateralization of cerebral activation towards the
      right hemisphere of early visual cortical areas and areas of higher-level visual
      processing, involved in visuospatial attention, especially in top-down (i.e.,
      goal-oriented) attentional processing. This right hemisphere lateralization was
      partly, but not completely, explained by an increased grey matter volume in the
      right hemisphere of the early visual areas. Difference in activation of the
      superior parietal lobule was correlated with subject age, suggesting a shift
      towards the left hemisphere with increasing age. Our findings suggest a right
      hemispheric dominance of these areas, which could lend support to the generally
      observed leftward visual attentional bias and to the left hemifield advantage for
      some visual perception tasks. 

PMID- 25985080
TI  - The impact of diabetes on employment in Mexico.
AB  - This study explores the impact of diabetes on employment in Mexico using data
      from the Mexican Family Life Survey (MxFLS) (2005), taking into account the
      possible endogeneity of diabetes via an instrumental variable estimation
      strategy. We find that diabetes significantly decreases employment probabilities
      for men by about 10 percentage points (p<0.01) and somewhat less so for women -
      4.5 percentage points (p<0.1)--without any indication of diabetes being
      endogenous. Further analysis shows that diabetes mainly affects the employment
      probabilities of men and women above the age of 44 and also has stronger effects
      on the poor than on the rich, particularly for men. We also find some indication
      for more adverse effects of diabetes on those in the large informal labour market
      compared to those in formal employment. Our results highlight--for the first time
      -the detrimental employment impact of diabetes in a developing country.

PMID- 25985081
TI  - Exploring the complex pattern of information spreading in online blog
      communities.
AB  - Information spreading in online social communities has attracted tremendous
      attention due to its utmost practical values in applications. Despite that
      several individual-level diffusion data have been investigated, we still lack the
      detailed understanding of the spreading pattern of information. Here, by
      comparing information flows and social links in a blog community, we find that
      the diffusion processes are induced by three different spreading mechanisms:
      social spreading, self-promotion and broadcast. Although numerous previous
      studies have employed epidemic spreading models to simulate information
      diffusion, we observe that such models fail to reproduce the realistic diffusion
      pattern. In respect to users behaviors, strikingly, we find that most users would
      stick to one specific diffusion mechanism. Moreover, our observations indicate
      that the social spreading is not only crucial for the structure of diffusion
      trees, but also capable of inducing more subsequent individuals to acquire the
      information. Our findings suggest new directions for modeling of information
      diffusion in social systems, and could inform design of efficient propagation
      strategies based on users behaviors. 

PMID- 25985083
TI  - RNA-Binding Proteins: Splicing Factors and Disease.
AB  - Pre-mRNA splicing is mediated by interactions of the Core Spliceosome and an
      array of accessory RNA binding proteins with cis-sequence elements. Splicing is a
      major regulatory component in higher eukaryotes. Disruptions in splicing are a
      major contributor to human disease. One in three hereditary disease alleles are
      believed to cause aberrant splicing. Hereditary disease alleles can alter
      splicing by disrupting a splicing element, creating a toxic RNA, or affecting
      splicing factors. One of the challenges of medical genetics is identifying causal
      variants from the thousands of possibilities discovered in a clinical sequencing
      experiment. Here we review the basic biochemistry of splicing, the mechanisms of
      splicing mutations, the methods for identifying splicing mutants, and the
      potential of therapeutic interventions. 

PMID- 25985084
TI  - Highly efficient and stable organic light-emitting diodes with a greatly reduced
      amount of phosphorescent emitter.
AB  - Organic light-emitting diodes (OLEDs) have been intensively studied as a key
      technology for next-generation displays and lighting. The efficiency of OLEDs has
      improved markedly in the last 15 years by employing phosphorescent emitters.
      However, there are two main issues in the practical application of phosphorescent
      OLEDs (PHOLEDs): the relatively short operational lifetime and the relatively
      high cost owing to the costly emitter with a concentration of about 10% in the
      emitting layer. Here, we report on our success in resolving these issues by the
      utilization of thermally activated delayed fluorescent materials, which have been
      developed in the past few years, as the host material for the phosphorescent
      emitter. Our newly developed PHOLED employing only 1 wt% phosphorescent emitter
      exhibits an external quantum efficiency of over 20% and a long operational
      lifetime of about 20 times that of an OLED consisting of a conventional host
      material and 1 wt% phosphorescent emitter. 

PMID- 25985082
TI  - Mechanisms of alpha-synuclein action on neurotransmission: cell-autonomous and
      non-cell autonomous role.
AB  - Mutations and duplication/triplication of the alpha-synuclein (alphaSyn)-coding
      gene have been found to cause familial Parkinson's disease (PD), while genetic
      polymorphisms in the region controlling the expression level and stability of
      alphaSyn have been identified as risk factors for idiopathic PD, pointing to the
      importance of wild-type (wt) alphaSyn dosage in the disease. Evidence that
      alphaSyn is present in the cerebrospinal fluid and interstitial brain tissue and
      that healthy neuronal grafts transplanted into PD patients often degenerate
      suggests that extracellularly-released alphaSyn plays a role in triggering the
      neurodegenerative process. alphaSyn's role in neurotransmission has been shown in
      various cell culture models in which the protein was upregulated or deleted and
      in knock out and transgenic animal, with different results on alphaSyn's effect
      on synaptic vesicle pool size and mobilization, alphaSyn being proposed as a
      negative or positive regulator of neurotransmitter release. In this review, we
      discuss the effect of alphaSyn on pre- and post-synaptic compartments in terms of
      synaptic vesicle trafficking, calcium entry and channel activity, and we focus on
      the process of exocytosis and internalization of alphaSyn and on the spreading of
      alphaSyn-driven effects due to the presence of the protein in the extracellular
      milieu. 

PMID- 25985085
TI  - Limits on information transduction through amplitude and frequency regulation of
      transcription factor activity.
AB  - Signaling pathways often transmit multiple signals through a single shared
      transcription factor (TF) and encode signal information by differentially
      regulating TF dynamics. However, signal information will be lost unless it can be
      reliably decoded by downstream genes. To understand the limits on dynamic
      information transduction, we apply information theory to quantify how much gene
      expression information the yeast TF Msn2 can transduce to target genes in the
      amplitude or frequency of its activation dynamics. We find that although the
      amount of information transmitted by Msn2 to single target genes is limited,
      information transduction can be increased by modulating promoter cis-elements or
      by integrating information from multiple genes. By correcting for extrinsic
      noise, we estimate an upper bound on information transduction. Overall, we find
      that information transduction through amplitude and frequency regulation of Msn2
      is limited to error-free transduction of signal identity, but not signal
      intensity information. 

PMID- 25985086
TI  - Quantitative isoform-profiling of highly diversified recognition molecules.
AB  - Complex biological systems rely on cell surface cues that govern cellular self
      recognition and selective interactions with appropriate partners. Molecular
      diversification of cell surface recognition molecules through DNA recombination
      and complex alternative splicing has emerged as an important principle for
      encoding such interactions. However, the lack of tools to specifically detect and
      quantify receptor protein isoforms is a major impediment to functional studies.
      We here developed a workflow for targeted mass spectrometry by selected reaction
      monitoring that permits quantitative assessment of highly diversified protein
      families. We apply this workflow to dissecting the molecular diversity of the
      neuronal neurexin receptors and uncover an alternative splicing-dependent
      recognition code for synaptic ligands. 

PMID- 25985088
TI  - Investigation of susceptibility genes triggering lachrymal/salivary gland lesion
      complications in Japanese patients with type 1 autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis
      characterized by high serum IgG4 concentration and a variety of complicating
      extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to
      manifest in a highly active AIP disease state, and several genes are speculated
      to be associated with the onset of this complication. We therefore searched for
      candidate susceptibility genes related to lachrymal/salivary gland lesions in a
      genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array
      Set (Affymetrix, CA) that was followed by fine mapping of additional single
      nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays.
      Venous blood samples were obtained from 50 type 1 AIP patients with
      lachrymal/salivary gland lesions (A group) and 53 type 1 AIP patients without (B
      group). The mean values of IgG and IG4 were both significantly different (P<0.05)
      between the groups. SNPs that showed a significant association with the A group
      at the genome-wide level (P<0.0001) were identified and subsequently used in fine
      SNP mapping of candidate genes. In total, five SNPs had a positive association
      with complicated AIP (most notably rs2284932 [P=0.0000021]) and five SNPs
      possessed a negative association (particularly rs9371942 [P=0.00000039]). Among
      them, KLF7, FRMD4B, LOC101928923, and MPPED2 were further examined for
      complication susceptibility using additional SNPs that were not included in the
      GWAS. Individual genotyping of KLF7 rs2284932 revealed that the frequency of the
      minor C allele was significantly increased (P = 0.00062, Pc = 0.003, OR = 2.98,
      95%CI = 1.58-5.65) in group A. The minor T allele of rs4473559 in FRMD4
      demonstrated a significant association in the A group (P = 0.00015, OR = 3.38,
      95%CI = 1.77-6.45). In the LOC101928923 gene, the frequency of the minor T allele
      of rs4379306 was significantly decreased in group A in both TaqMan and GWAS
      analyses. Lastly, the minor C allele of MPPED2 rs514644 carried a significantly
      increased risk of complications [corrected].These four genes may be linked with
      the onset of lachrymal/salivary gland lesions in type 1 AIP patients and require
      further study.

PMID- 25985089
TI  - A pilot study to explore the experiences of congenitally or early profoundly
      deafened candidates who receive cochlear implants as adults.
AB  - OBJECTIVES: To explore the experiences of congenitally or early profoundly
      deafened candidates who receive cochlear implants as adults. METHODS: Eight
      congenitally or early profoundly deafened implantees who had received their
      implants as adults were interviewed using a semi-structured interview technique.
      Interviews were conducted in the participant's preferred communication mode
      (oral/aural, Sign Supported English, or British Sign Language). RESULTS: All
      participants reported benefit from implantation. Areas of benefit identified
      correspond with results from similar studies conducted with post-lingually
      deafened adult implantees. DISCUSSION: Congenitally or early profoundly deafened
      adults implanted as adults report benefit from cochlear implantation in the
      following areas: identity, hearing the world, and emotional wellbeing. They also
      commented on their motivation for wanting an implant and the advice they would
      give to others considering implantation.

PMID- 25985087
TI  - A FYVE zinc finger domain protein specifically links mRNA transport to endosome
      trafficking.
AB  - An emerging theme in cellular logistics is the close connection between mRNA and
      membrane trafficking. A prominent example is the microtubule-dependent transport
      of mRNAs and associated ribosomes on endosomes. This coordinated process is
      crucial for correct septin filamentation and efficient growth of polarised cells,
      such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein
      and the molecular motors involved, it is unclear how mRNAs are connected to
      membranes during transport. Here, we identify a novel factor containing a FYVE
      zinc finger domain for interaction with endosomal lipids and a new PAM2-like
      domain required for interaction with the MLLE domain of the key RNA-binding
      protein. Consistently, loss of this FYVE domain protein leads to specific defects
      in mRNA, ribosome, and septin transport without affecting general functions of
      endosomes or their movement. Hence, this is the first endosomal component
      specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to
      endosomes. 

PMID- 25985090
TI  - Strategy for Nuclear-Magnetic-Resonance-Based Metabolomics of Human Feces.
AB  - Metabolomic analyses of fecal material are gaining increasing attention because
      the gut microbial ecology and activity have an impact on the human phenotype and
      regulate host metabolism. Sample preparation is a crucial step, and in this
      study, we recommend a methodology for extraction and analysis of fresh feces by
      NMR-based metabolomics. The evaluation of extraction solvents showed that buffer
      extraction is a suitable approach to extract metabolic information in feces.
      Therefore, the effects of weight-to-buffer (Wf:Vb) combinations and the effect of
      sonication and freeze-thaw cycles on the reproducibility, chemical shift
      variability, and signal-to-noise ratio (SNR) of the (1)H NMR spectra were
      evaluated. On the basis of our results, we suggest that fresh fecal extraction
      with a Wf:Vb ratio of 1:2 may be the optimum choice to determine the overall
      metabolite composition of feces. In fact, more than 60 metabolites have been
      assigned in the NMR spectra obtained from the fresh fecal buffer extract, and
      assignments of the lipophilic signals are also presented. To our knowledge, some
      of the metabolites are reported here for the very first time employing (1)H NMR
      spectroscopy on human fecal extracts. 

PMID- 25985091
TI  - Commingling effect of gynoid and android fat patterns on cardiometabolic
      dysregulation in normal weight American adults.
AB  - AIM: To determine the independent and commingling effect of android and gynoid
      percent fat (measured using Dual Energy X-Ray Absorptiometry) on cardiometabolic
      dysregulation in normal weight American adults. METHODS: The 2005-2006 data
      (n=1802) from the United States National Health and Nutritional Examination
      Surveys (NHANES) were used in this study. Associations of android percent fat,
      gynoid percent fat and their joint occurrence with risks of cardiometabolic risk
      factors were estimated using prevalence odds ratios from logistic regression
      analyses. RESULTS: Android-gynoid percent fat ratio was more highly correlated
      with cardiometabolic dysregulation than android percent fat, gynoid percent fat
      or body mass index. Commingling of android and gynoid adiposities was associated
      with much greater odds of cardiometabolic risk factors than either android or
      gynoid adiposities. Commingling of android and gynoid adiposities was associated
      with 1.75 (95% confidence interval (CI)=1.42-2.93), 1.48 (95% CI=1.32-1.91), 1.61
      (95% CI=1.50-1.89), 3.56 (95% CI=2.91-4.11) and 1.86 (95% CI=1.49-1.96) increased
      odds of elevated glucose, elevated blood pressure, elevated low-density
      lipoprotein-cholesterol, elevated triglyceride and low high-density lipoprotein
      cholesterol, respectively. CONCLUSIONS: Normal weight subjects who present with
      both android and gynoid adiposities should be advised of the associated health
      risks. Both android and gynoid fat accumulations should be considered in
      developing public health strategies for reducing cardiometabolic disease risk in
      normal weight subjects.

PMID- 25985092
TI  - Comparative effect of intraduodenal and intrajejunal glucose infusion on the gut
      incretin axis response in healthy males.
AB  - The region of enteral nutrient exposure may be an important determinant of
      postprandial incretin hormone secretion and blood glucose homoeostasis. We
      compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent
      insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a
      standardised glucose infusion into the proximal jejunum and duodenum in healthy
      humans. Ten healthy males were evaluated during a standardised glucose infusion
      (2 kcal min(-1) over 120 min) into the proximal jejunum (50 cm post pylorus) and
      were compared with another 10 healthy males matched for ethnicity, age and body
      mass index who received an identical glucose infusion into the duodenum (12 cm
      post pylorus). Blood was sampled frequently for measurements of blood glucose and
      plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the
      insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05
      for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without
      a significant difference in blood glucose or plasma glucagon. Pooled analyses
      revealed direct relationships between IGI1 and the responses of GLP-1 and GIP
      (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1
      (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone
      and insulin secretion than intraduodenal glucose in healthy humans, suggesting
      regional specificity of the gut-incretin axis. 

PMID- 25985093
TI  - Assessment of predation risk through referential communication in incubating
      birds.
AB  - Parents of many bird species produce alarm calls when they approach and deter a
      nest predator in order to defend their offspring. Alarm calls have been shown to
      warn nestlings about predatory threats, but parents also face a similar risk of
      predation when incubating eggs in their nests. Here, I show that incubating
      female Japanese great tits, Parus minor, assess predation risk by conspecific
      alarm calls given outside the nest cavity. Tits produce acoustically discrete
      alarm calls for different nest predators: "jar" calls for snakes and "chicka"
      calls for other predators such as crows and martens. Playback experiments
      revealed that incubating females responded to "jar" calls by leaving their nest,
      whereas they responded to "chicka" calls by looking out of the nest entrance.
      Since snakes invade the nest cavity, escaping from the nest helps females avoid
      snake predation. In contrast, "chicka" calls are used for a variety of predator
      types, and therefore, looking out of the nest entrance helps females gather
      information about the type and location of approaching predators. These results
      show that incubating females derive information about predator type from
      different types of alarm calls, providing a novel example of functionally
      referential communication. 

PMID- 25985094
TI  - Imaging Correlates of Memory and Concussion History in Retired National Football
      League Athletes.
AB  - IMPORTANCE: To our knowledge, this is the first study to show an association
      between concussion, cognition, and anatomical structural brain changes across the
      age spectrum in former National Football League athletes. OBJECTIVE: To assess
      the relationship of hippocampal volume, memory performance, and the influence of
      concussion history in retired National Football League athletes with and without
      mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS: This
      retrospective cohort study assessed differences between groups, mean hippocampal
      volumes, and memory performance by computing age quintiles based on group
      specific linear regression models corrected for multiple comparisons for both
      athletes and control participants. The study was conducted starting in November
      2010 and is ongoing at a research center in the northern region of Texas. This
      current analysis was conducted from October 9, 2013, to August 21, 2014.
      Participants included 28 retired National Football League athletes, 8 of whom had
      MCI and a history of concussion, 21 cognitively healthy control participants, and
      6 control participants with MCI without concussion. MAIN OUTCOMES AND MEASURES:
      Hippocampal volume, age, California Verbal Learning Test scores, and the number
      of grade 3 (G3) concussions. In addition, the number of games played was examined
      as an objective variable pertaining to football history. RESULTS: The mean (SD)
      age was 58.1 (13) years for the 28 former athletes and 59.0 (12) years for the 27
      control participants. Retired athletes with concussion history but without
      cognitive impairment had normal but significantly lower California Verbal
      Learning Test scores compared with control participants (mean [SD], 52.5 [8] vs
      60.24 [7]; P = .002); those with a concussion history and MCI performed worse
      (mean [SD], 37 [8.62]) compared with both control participants (P < .001) and
      athletes without memory impairment (P < .001). Among the athletes, 17 had a G3
      concussion and 11 did not. Older retired athletes with at least 1 G3 concussion
      had significantly smaller bilateral hippocampal volumes compared with control
      participants at the 40th age percentile (left, P = .04; right, P = .03), 60th
      percentile (left, P = .009; right, P = .01), and 80th percentile (left, P = .001;
      right, P = .002) and a smaller right hippocampal volume compared with athletes
      without a G3 concussion at the 40th percentile (P = .03), 60th percentile (P =
      .02), and 80th percentile (P = .02). Athletes with a history of G3 concussion
      were more likely to have MCI (7 of 7) compared with retired athletes without a
      history of G3 concussion (1 of 5) older than 63 years (P = .01). In addition, the
      left hippocampal volume in retired athletes with MCI and concussion was
      significantly smaller compared with control participants with MCI (P = .03).
      CONCLUSION AND RELEVANCE: Prior concussion that results in loss of consciousness
      is a risk factor for increased hippocampal atrophy and the development of MCI. In
      individuals with MCI, hippocampal volume loss appears greater among those with a
      history of concussion.

PMID- 25985095
TI  - Gene transcription, metabolite and lipid profiling in eco-indicator daphnia magna
      indicate diverse mechanisms of toxicity by legacy and emerging flame-retardants.
AB  - The use of chemical flame-retardants (FR) in consumer products has steadily
      increased over the last 30 years. Toxicity data exist for legacy FRs such as
      pentabromodiphenyl ether (pentaBDE), but less is known about effects of new
      formulations. To address this issue, the toxicity of seven FR chemicals and
      formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h
      nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE),
      Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl)
      tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH
      TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE)
      to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic
      profiling at 1/10 LC50 revealed distinct patterns of molecular response for each
      exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and
      BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog
      signal pathways as well as glycosaminoglycan degradation. Brominated components
      of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following
      1/10 LC50 exposure. FM550 elicited significant mRNA changes at five
      concentrations across a range from 1/10(6) LC50 to 1/2 LC50. Analyses suggest
      FM550 impairs nutrient utilization or uptake in Daphnia.

PMID- 25985097
TI  - Evaluating the degradation, sorption, and negative mass balances of
      pharmaceuticals and personal care products during wastewater treatment.
AB  - Conventional activated sludge (CAS) wastewater treatment processes are
      insufficient at removing many pharmaceutical and personal care products (PPCPs)
      from wastewater. In addition, negative mass balances, where the effluent
      concentration is greater than the influent concentration, have been observed in
      wastewater treatment studies and a further understanding of these results is
      needed. In this study, the fate and occurrence of 57 PPCPs and hormones were
      evaluated in an activated sludge process and the mass balances were determined.
      The goal of the project was to understand the PPCPs biological degradation and
      the extent of sorption to solids. The samples containing in situ PPCPs (i.e.
      samples were not spiked with additional PPCPs) were evaluated. Forty-eight of the
      PPCPs were detected in the soluble form and 29 were detected sorbed to solids.
      Two notable results were found. First, the results of this study indicate a
      subset of the highly biodegradable PPCPs stop being degraded at low, yet notable,
      concentrations. Second, the results revealed that negative mass balances were
      present for a subset of the PPCPs when evaluating both the soluble and sorbed
      concentration, for example carbamazepine and ofloxacin. Desorption from solids
      was not found to attribute to negative mass balances. Overall, the results from
      this study provide new insights into the fate of PPCPs during CAS wastewater
      treatment by evaluating the degradation kinetics and sorption and the results may
      explain the consistent levels of highly degradable PPCPs being emitted from WWTPs
      worldwide. 

PMID- 25985096
TI  - Optimal flushing agents for integrated optical and acoustic imaging systems.
AB  - An increasing number of integrated optical and acoustic intravascular imaging
      systems have been developed and hold great promise for accurately diagnosing
      vulnerable plaques and guiding atherosclerosis treatment. However, in any
      intravascular environment, the vascular lumen is filled with blood, a high
      scattering source for optical and high-frequency ultrasound signals. Blood must
      be flushed away to provide clearer images. To our knowledge, no research has been
      performed to find the ideal flushing agent for combined optical and acoustic
      imaging techniques. We selected three solutions as potential flushing agents for
      their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these
      flushing agents was performed in a closed-loop circulation model and in vivo on
      rabbits. We found that a high concentration of dextran was the most useful for
      simultaneous intravascular ultrasound and optical coherence tomography imaging.

PMID- 25985098
TI  - Measurement and ANN prediction of pH-dependent solubility of nitrogen
      heterocyclic compounds.
AB  - Based on the solubility of 25 nitrogen-heterocyclic compounds (NHCs) measured by
      saturation shake-flask method, artificial neural network (ANN) was employed to
      the study of the quantitative relationship between the structure and pH-dependent
      solubility of NHCs. With genetic algorithm-multivariate linear regression (GA
      MLR) approach, five out of the 1497 molecular descriptors computed by Dragon
      software were selected to describe the molecular structures of NHCs. Using the
      five selected molecular descriptors as well as pH and the partial charge on the
      nitrogen atom of NHCs (QN) as inputs of ANN, a quantitative structure-property
      relationship (QSPR) model without using Henderson-Hasselbalch (HH) equation was
      successfully developed to predict the aqueous solubility of NHCs in different pH
      water solutions. The prediction model performed well on the 25 model NHCs with an
      absolute average relative deviation (AARD) of 5.9%, while HH approach gave an
      AARD of 36.9% for the same model NHCs. It was found that QN played a very
      important role in the description of NHCs and, with QN, ANN became a potential
      tool for the prediction of pH-dependent solubility of NHCs. 

PMID- 25985099
TI  - Modeling fungicides mobility in undisturbed vineyard soil cores unamended and
      amended with spent mushroom substrates.
AB  - The performance of the pesticide fate model PRZM to predict the fate of two
      fungicides, penconazole and metalaxyl, and the major metabolite of metalaxyl (CGA
      62826), in amended and unamended vineyard soils was tested from undisturbed soils
      columns experiments. Three different treatments were tested in two soils: control
      soil (unamended), and soil amended with fresh or composted spent mushroom
      substrates, which correspond to common agricultural practices in Spain. Leaching
      experiments were performed under non-saturated flow conditions. The model was
      parameterized with laboratory and literature data, and using pedotransfer
      functions. It was first calibrated for water flow against chloride breakthrough
      curves. The key parameter was the hydrodynamic dispersion coefficient (DISP). No
      leaching of penconazole, the most hydrophobic fungicide, was observed. It
      remained in the top 0-8 cm of the column. In any case, simulations were highly
      correlated to the experimental results. On the contrary, metalaxyl and its
      metabolite were consistently found in the leachates. A calibration step of the Kd
      of metalaxyl and CGA-62826 and of DISP for CGA-62826 was necessary to obtain good
      prediction of the leaching of both compounds. PRZM generally simulated acceptable
      metalaxyl vertical distribution in the soil profiles although results were
      overestimated for its metabolite. Nevertheless, PRZM can be reasonably used to
      assess the leaching (through breakthrough curves) and vertical distribution of
      fungicides in amended soils, knowing their DISP values.

PMID- 25985100
TI  - Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain
      at Hospital Admission.
AB  - IMPORTANCE: Patients with potentially ischemic chest pain are commonly admitted
      to the hospital or observed after a negative evaluation in the emergency
      department (ED) owing to concern about adverse events. Previous studies have
      looked at 30-day mortality, but no current large studies have examined the most
      important information regarding ED disposition: the short-term risk for a
      clinically relevant adverse cardiac event (including inpatient ST-segment
      elevation myocardial infarction, life-threatening arrhythmia, cardiac or
      respiratory arrest, or death). OBJECTIVE: To determine the incidence of
      clinically relevant adverse cardiac events in patients hospitalized for chest
      pain with 2 troponin-negative findings, nonconcerning initial ED vital signs, and
      nonischemic, interpretable electrocardiographic findings. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted a blinded data review of 45,416 encounters obtained
      from a prospectively collected database enrolling adult patients admitted or
      observed with the following inclusion criteria: (1) primary presenting symptom of
      chest pain, chest tightness, chest burning, or chest pressure and (2) negative
      findings for serial biomarkers. Data were collected and analyzed from July 1,
      2008, through June 30, 2013, from the EDs of 3 community teaching institutions
      with an aggregate census of more than 1 million visits. We analyzed data
      extracted by hypothesis-blinded abstractors. MAIN OUTCOMES AND MEASURES: The
      primary outcome was a composite of life-threatening arrhythmia, inpatient ST
      segment elevation myocardial infarction, cardiac or respiratory arrest, or death
      during hospitalization. RESULTS: Of the 45,416 encounters, 11,230 met criteria
      for inclusion. Mean patient age was 58.0 years. Of the 11 230 encounters, 44.83%
      of patients arrived by ambulance and 55.00% of patients were women. Relevant
      history included hypertension in 46.00%, diabetes mellitus in 19.72%, and
      myocardial infarction in 13.16%. The primary end point occurred in 20 of the 11
      230 patients (0.18% [95% CI, 0.11%-0.27%]). After excluding patients with
      abnormal vital signs, electrocardiographic ischemia, left bundle branch block, or
      a pacemaker rhythm, we identified a primary end point event in 4 of 7266 patients
      (0.06% [95% CI, 0.02%-0.14%]). Of these events, 2 were noncardiac and 2 were
      possibly iatrogenic. CONCLUSIONS AND RELEVANCE: In adult patients with chest pain
      admitted with 2 negative findings for serial biomarkers, nonconcerning vital
      signs, and nonischemic electrocardiographic findings, short-term clinically
      relevant adverse cardiac events were rare and commonly iatrogenic, suggesting
      that routine inpatient admission may not be a beneficial strategy for this group.

PMID- 25985101
TI  - A comparison of two questionnaires on Informed Consent for extended criteria
      liver donors.
AB  - AIM: A questionnaire concerning informed recipient's consent for "extended
      criteria liver donors"(ECD), after approval of the Institutional Review
      Board(IRB), was sent in different times by e-mail to members of 2 scientific
      societies, ELPAT (Ethical,Legal and Psychologic Aspects of Organ Transplantation)
      and ELITA (European Liver and Intestine Transplant Association)-ELTR(European
      Liver Transplant Registry. MATERIALS AND METHODS: The results were published in
      different papers in Transplantation Proceedings. RESULTS: By comparing tables in
      the 2011 ELPAT and 2013 ELITA papers, in the most recent paper less Liver
      Transplant Centers(LTC) considered age as high as 80 years (p<.002)and SGOT>90 IU
      (p<.02), or all criteria together (p<.0001), as indicators of ECD. DISCUSSION:
      This may reflects the fact that more recently LTC have become less selective, due
      to the rising mortality in the increasing liver transplant waiting list. In all
      these studies we highlighted both a disparity of practice across centres and the
      relatively large contribution made by ECD livers to the transplantation effort.
      CONCLUSIONS: Therefore patients should receive all the required informations
      concerning the quality of the liver offered to them for transplantation, not only
      when they are enlisted, but also when the liver becomes available and is proposed
      to them. It is also possible to create a special waiting list of patients not
      accepting ECD, although this option could delay liver transplantation and
      consequently increase mortality.

PMID- 25985102
TI  - Revisiting the endocytosis of the m2 muscarinic acetylcholine receptor.
AB  - The agonist-induced endocytosis of the muscarinic acetylcholine receptor M2 is
      different from that of the other members of the muscarinic receptor family. The
      uptake of the M2 receptor involves the adapter proteins of the beta-arrestin
      family and the small GTPase ADP-ribosylation factor 6. However, it has remained
      inconclusive if M2 endocytosis is dependent on clathrin or the large GTPase
      dynamin. We here show by means of knocking down the clathrin heavy chain that M2
      uptake upon agonist stimulation requires clathrin. The expression of various
      dominant-negative dynamin-2 mutants and the use of chemical inhibitors of dynamin
      function revealed that dynamin expression and membrane localization as such
      appear to be necessary for M2 endocytosis, whereas dynamin GTPase activity is not
      required for this process. Based on the data from the present and from previous
      studies, we propose that M2 endocytosis takes place by means of an atypical
      clathrin-mediated pathway that may involve a specific subset of clathrin-coated
      pits/vesicles. 

PMID- 25985103
TI  - Increased P-wave dispersion a risk for atrial fibrillation in adolescents with
      anorexia nervosa.
AB  - Studies have shown that a prolonged P-wave dispersion is a risk factor for the
      development of atrial fibrillation. The aim of this study was to evaluate P-wave
      dispersion in adolescents with anorexia nervosa at diagnosis. We evaluated
      electrocardiographic findings, particularly the P-wave dispersion, at initial
      assessment in 47 adolescents with anorexia nervosa. Comparison of P-wave
      dispersion between adolescents with anorexia nervosa and controls showed a
      statistically significant higher P-wave dispersion in patients with anorexia
      nervosa (72 +/- 16.3 msec) when compared to the control group (43.8 +/- 9.5
      msec). Percent of body weight lost, lower body mass index, and higher weight loss
      rate in the patients with anorexia nervosa had no effect on P-wave dispersion.
      Due to the fact that anorexia nervosa has a high mortality rate we believe that
      cardiac pathologies such as atrial fibrillation must also be considered in the
      medical evaluation. 

PMID- 25985104
TI  - The new normal? Addressing gun violence in America.

PMID- 25985105
TI  - Defying the odds on gun regulation: The passage of bipartisan mental health laws
      across the states.

PMID- 25985106
TI  - Challenging the political assumption that "Guns don't kill people, crazy people
      kill people!".

PMID- 25985107
TI  - Our schools are safe: Challenging the misperception that schools are dangerous
      places.

PMID- 25985108
TI  - Preventing the invisible plague of firearm suicide.

PMID- 25985109
TI  - A broader perspective of gun control.

PMID- 25985110
TI  - The Danieli Inventory of Multigenerational Legacies of Trauma, Part II:
      Reparative Adaptational Impacts.
AB  - The impacts of the Holocaust on children of survivors have been widely
      investigated. However, consensus is limited, and no validated measures have been
      tailored with or to them. We aimed to develop and validate a scale that measures
      these specific impacts (Part II of the Danieli Inventory of Multigenerational
      Legacies of Trauma). We studied 484 adult children of survivors who participated
      in a cross-sectional web-based survey in English or Hebrew; of these, 191
      participated in a clinical interview. Exploratory factor analyses of 58 items to
      reduce and refine the measure yielded a 36-item scale, Reparative Adaptational
      Impacts, that had excellent internal consistency (alpha = .91) and congruence
      between English and Hebrew versions (phi >= .95). Associations between impacts
      and SCID-based diagnoses of major depressive episode, posttraumatic stress
      disorder, and generalized anxiety disorder were moderate to strong (ds = 0.48
      0.89). Strong associations also emerged between severity of offspring's
      reparative adaptational impacts and intensity of their parents' posttrauma
      adaptational styles (Multiple R = .72), with intensity of victim style,
      especially the mother's, having the strongest effect (beta = .31-.33). Having
      both research and clinical relevance for assessing Holocaust survivors'
      offspring, future studies might investigate the scale's generalizability to other
      populations affected by mass trauma.

PMID- 25985111
TI  - A structural equation modeling study of the Spanish Mental Illness Stigma
      Attribution Questionnaire (AQ-27-E).
AB  - The main purpose of this study was the translation and analysis of psychometric
      properties of the Attribution Questionnaire for use in Spanish-speaking
      populations (AQ-27-E) and to test the dangerousness and responsibility models of
      mental illness stigma in a Spanish sample. The sample consisted of 439 adults
      from the general population of the community of Madrid (Spain). The questionnaire
      was translated using the translation/back-translation method. Cronbach's alpha
      was used to carry out the reliability analysis, and structural equations were
      used to test the dangerousness and the responsibility models of stigma. Internal
      reliability of AQ-27-E was .855, which can be interpreted as good. However, some
      factors (Pity, Responsibility, and Coercion) showed limited internal consistency.
      Results suggest that the AQ-27-E is a standardized instrument with acceptable
      psychometric properties comparable to previous versions, which can be used to
      assess stigma in Spanish-speaking populations.

PMID- 25985112
TI  - Impact of Inuit customary adoption on behavioral problems in school-age Inuit
      children.
AB  - A large proportion of Inuit children in Arctic Quebec are adopted in accordance
      with traditional Inuit customs. In contrast to adoptions in Southern Canada and
      the United States, the child is adopted at birth and by a close family member; he
      or she knows who his or her biological parents are, and will typically have
      contact with them. Studies of other populations have reported an increased
      incidence of behavior problems in adopted compared with nonadopted children. This
      study examined the actual extent of the increase in the number of behavior
      problems seen in Inuit children adopted in accordance with traditional customs.
      In a prospective longitudinal study conducted in the Canadian Arctic (n = 46
      adopted and 231 nonadopted children), prenatal and familial variables were
      documented at birth and at school age (M = 11.3 years). Behavior problems were
      assessed on the Teacher Report Form of the Child Behavior Checklist. Adopted
      children lived in more economically disadvantaged families, but their caregivers
      were less prone to depression, domestic violence, or alcohol abuse compared with
      those of the nonadopted children. The adoption status was not related to the
      teacher's report of attention problems, externalizing or internalizing behaviors,
      after controlling for confounders. Despite less favorable socioeconomic
      circumstances, a higher extent of behavioral problems was not seen at school age
      in Inuit children adopted at birth by a family member. Psychosocial stressors
      associated with adoption are more likely to be responsible for an association
      with higher levels of childhood behavior problems rather than adoption per se.

PMID- 25985113
TI  - Risk for behavior problems in children of parents with substance use disorders.
AB  - Using a high-risk community sample (N = 567), the current study examined risk for
      externalizing and internalizing problems in the children of parents with
      recovered and current substance use disorders (SUDs). This study also tested
      whether parenting mediated the relations between these variables. Results suggest
      that children of parents with current diagnoses were at elevated risk for
      externalizing and internalizing problems, but children of parents with recovered
      diagnoses were only at risk for externalizing problems. Perceived parental
      consistency of support mediated the relations between parent current SUD and
      child externalizing and internalizing problems. Disruption of the home
      environment may in part explain why children of parents with SUDs are at risk for
      externalizing and internalizing problems. However, even after parent SUD has
      remitted, children remain at risk for externalizing problems, suggesting multiple
      mechanisms by which parents confer risk for psychopathology.

PMID- 25985114
TI  - Asylum-seeking children's experiences of detention in Canada: A qualitative
      study.
AB  - Children and parents seeking asylum are regularly detained in Canada, however
      little is known about the experiences of detained families. International
      literature suggests that the detention of children is associated with significant
      morbidity. Our study aims to understand the experiences of detained children and
      families who have sought asylum in Canada by using a qualitative methodology that
      includes semistructured interviews and ethnographic participant observation.
      Detention appears to be a frightening experience of deprivation that leaves
      children feeling criminalized and helpless. Family separation further shatters
      children's sense of well-being. Children's emotional and behavioral responses to
      separation and to detention suggest that the experience is acutely stressful and,
      in some cases, traumatic--even when detention is brief. Distress and impairment
      may persist months after release. Given the burden of psychological suffering and
      the harmful consequences of separating families, children should not be detained
      for immigration reasons and parents should not be detained without children.

PMID- 25985115
TI  - Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl
      alcohol) Physical Hydrogel.
AB  - Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time
      with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The
      addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a
      strong hydrogel due to the multiple H-bonding between the two constituents. A
      temporary shape of the hydrogel can be obtained by deformation of the hydrogel
      (~65 wt % water) at room temperature, followed by fixation of the deformation by
      freezing/thawing the hydrogel under strain, which induces crystallization of PVA.
      We show that the ultrasound delivered by a commercially available device designed
      for the patient's pain relief could trigger the shape recovery process as a
      result of ultrasound-induced local heating in the hydrogel that melts the
      crystallized PVA cross-linking. This hydrogel is thus interesting for potential
      applications because it combines many desirable properties, being mechanically
      strong, biocompatible, and self-healable and displaying the shape memory
      capability triggered by a physiological stimulus. 

PMID- 25985116
TI  - Nickel-Catalyzed Alkynylation of a C(sp(2))-H Bond Directed by an 8
      Aminoquinoline Moiety.
AB  - An efficient nickel catalyst system for the direct ortho C-H alkynylation of the
      amides has been successfully developed with the directing assistance of 8
      aminoquinoline. It was found that the flexible bis(2-dimethylaminoethyl) ether
      (BDMAE) ligand was critical to achieve the optimized reactivity. This protocol
      showed good tolerance toward not only a wide range of (hetero)aryl amides but
      also the rarely studied alpha,beta-unsaturated alkenyl amide. The directing amide
      group could be easily transformed to aldehyde or ester in high yields. Meanwhile,
      the removable TIPS substituent on the resultant aryl/alkenyl alkynes could be
      further converted to an aryl moiety through a Sila-Sonogashira coupling reaction.
      This Ni-catalyzed alkynylation procedure provides an alternative approach to
      construct a C(sp(2))-C(sp) bond. 

PMID- 25985118
TI  - Inflammatory bowel disease education: I can hear the extension for community
      healthcare outcomes.

PMID- 25985119
TI  - A day at the improv.

PMID- 25985117
TI  - A systematic investigation based on microRNA-mediated gene regulatory network
      reveals that dysregulation of microRNA-19a/Cyclin D1 axis confers an oncogenic
      potential and a worse prognosis in human hepatocellular carcinoma.
AB  - MicroRNAs (miRNAs) contribute to a wide variety of human diseases by regulating
      gene expression, leading to imbalances in gene regulatory networks. To discover
      novel hepatocellular carcinoma (HCC)-related miRNA-target axes and to elucidate
      their functions, we here performed a systematic investigation combining
      biological data acquisition and integration, miRNA-target prediction, network
      construction, functional assay and clinical validation. As a result, a total of
      117 HCC differentially expressed miRNAs were identified, and 728 high confident
      target genes of these miRNAs were collected. Then, the interaction network of
      target genes was constructed and 221 key nodes with topological importance in the
      network were identified according to their topological features including degree,
      node-betweenness, closeness and K-coreness. Among these key nodes, Cyclin D1 had
      the highest node-betweenness, implying its bottleneck role in the network.
      Luciferase reporter assay confirmed that miRNA-19a, which was one of HCC
      downregulated miRNAs, directly targeted Cyclin D1 in HCC cells. Moreover, miR-19a
      might play inhibitory roles in HCC malignancy via regulating Cyclin D1
      expression. Further clinical evidence also highlighted the prognostic potential
      of miR-19a/Cyclin D1 axis in HCC. In conclusion, this systematic investigation
      provides a framework to identify featured miRNAs and their target genes which are
      potent effectors in the occurrence and development of HCC. More importantly, miR
      19a/Cyclin D1 axis might have promising applications as a therapeutic target and
      a prognostic marker for patients with HCC. 

PMID- 25985120
TI  - Through the looking glass: Predictive and adaptive capacity in a time of great
      change.

PMID- 25985121
TI  - Tobacco control campaign in Uruguay: Impact on smoking cessation during pregnancy
      and birth weight.
AB  - We analyzed a nationwide registry of all pregnancies in Uruguay during 2007-2013
      to assess the impact of three types of tobacco control policies: (1) provider
      level interventions aimed at the treatment of nicotine dependence, (2) national
      level increases in cigarette taxes, and (3) national-level non-price regulation
      of cigarette packaging and marketing. We estimated models of smoking cessation
      during pregnancy at the individual, provider and national levels. The rate of
      smoking cessation during pregnancy increased from 15.4% in 2007 to 42.7% in 2013.
      National-level non-price policies had the largest estimated impact on cessation.
      The price response of the tobacco industry attenuated the effects of tax
      increases. While provider-level interventions had a significant effect, they were
      adopted by relatively few health centers. Quitting during pregnancy increased
      birth weight by an estimated 188 g. Tobacco control measures had no effect on the
      birth weight of newborns of non-smoking women.

PMID- 25985122
TI  - An on-line spectrophotometric determination of trace amounts of thiourea in tap
      water, orange juice, and orange peel samples using multi-channel flow injection
      analysis.
AB  - In this work, a flow injection analysis (FIA) method was introduced for the
      determination of trace amounts of thiourea in tap water. This method is based
      upon the inhibition effect of thiourea on the reaction between meta-cresol purple
      (MCP) and potassium bromate catalyzed by bromide ions in a sulfuric acid medium.
      In the presence of thiourea, an induction period appears in the reaction system,
      and as a result, the absorbance of MCP increases at 525 nm in the FIA manifold.
      The chemical and FIA variables are studied and optimized using the univariate and
      Simplex optimization methods. Under the optimum conditions, thiourea can be
      determined in the range of 0.100-13.0 MUg mL(-1). The limit of detection (3sigma)
      for thiourea was found to be 0.0310 MUg mL(-1). The relative standard deviations
      (RSDs) for six replicate determinations of 0.500, 5.00, and 12.0 MUg mL(-1) of
      thiourea were 4.0%, 1.8%, and 1.2%, respectively. The proposed method was also
      applied for the determination of thiourea in orange juice and orange peel samples
      with recoveries in the range of 98.0-101%. The analytical speed of the method was
      calculated to be about 120 sample per hour.

PMID- 25985123
TI  - RETRACTED: Neoteric FT-IR investigation on the functional groups of phosphonium
      based deep eutectic solvents.
AB  - Deep eutectic solvents (DESs) are novel solvent media that are currently under
      investigation as an alternative to ionic liquids and conventional solvents. The
      physical properties of DESs as well as their mild environmental footprint and
      potentially critical industrial application necessitate understanding the
      interaction of functional groups on both the salt and hydrogen bond donor (HBD).
      In this study, four DESs were prepared by mixing triethylenglycol,
      diethylenglycol, ethylenglycol, and glycerol as HBDs with
      methyltriphenylphosphonium bromide as a salt at a molar ratio of 1:4. Fourier
      transform infrared spectroscopy was conducted to highlight the chemical structure
      and mechanism of the combination of the four DESs. New spectra illustrating the
      combination of the functional groups of the HBDs and salt were observed and
      interpreted. This study is the first to investigate the properties of neoteric
      phosphonium-based DESs.

PMID- 25985124
TI  - Laser induced autofluorescence in the monitoring of beta-mercaptoethanol mediated
      photo induced proton coupled electron transfer in proteins.
AB  - Photo induced proton coupled electron transfer (PCET) is an important process
      that many organisms use for progression of catalytic reactions leading to energy
      conversion. In the present study, the influence of SDS and BME on the redox
      properties of tyrosine and tryptophan for five different globular proteins, BSA,
      HSA, RNase-A, trypsin and lysozyme were studied using laser induced
      autofluorescence. The proteins were subjected to denaturation under SDS, SDS plus
      heat and SDS plus beta-mercaptoethanol (BME) plus heat and the corresponding
      fluorescence were recorded. The influence of BME on the autofluorescence
      properties of the proteins were evaluated upon tris-2-corboxy-ethyl phosphine
      (TCEP) denaturation. The BSA and HSA when exposed to SDS alone, exhibited
      hydrophobic collapse around their tryptophan moieties. However, these proteins
      when treated with SDS plus BME plus heat, an unusual red shift in the emission
      was observed, may be due to proton transfer from hydroxyl group of the excited
      tyrosine residues to the local microenvironments. The observation was further
      confirmed with similar proton transfer in absence of tryptophan in RNase-A
      showing involvement of tyrosine in the process. A drastic quenching of
      fluorescence in all of the proteins under study were also observed, may be due to
      photo-induced electron transfer (PET) from BME to the intrinsic fluorophores
      resulting in radical ions formation, evaluated upon DCFDA measurements. 

PMID- 25985126
TI  - Synthesis, characterization and electrochemical studies of some Ni(II)Cu(II)
      heterobimetallic complexes derived from succinoyldihydrazones.
AB  - Synthesis, structural characterization and redox properties of three
      heterobimetallic complexes with formule {[NiCu(L(n))(CH3OH)3].CH3OH} using
      [Cu(H2L(n))(H2O)] as metalloligand have been demonstrated in the present paper.
      Electronic spectroscopy suggests that the copper center has a pseudo square
      pyramidal stereochemistry in all the complexes while the nickel center has a
      distorted octahedral stereochemistry. The electron transfer reactions of the
      complexes have been investigated by cyclic voltammetry. 

PMID- 25985125
TI  - Fluorescence quenching for chloramphenicol detection in milk based on protein
      stabilized Au nanoclusters.
AB  - In the present study, we report a simple and rapid method for sensitive and
      selective determination of chloramphenicol (CAP) based on fluorescence of bovine
      serum albumin-stabilized Au nanoclusters (BSA-AuNCs). The BSA-AuNCs exhibit
      strong red emission. Upon addition of CAP to BSA-AuNCs, the fluorescence
      intensity of AuNCs shows a dramatic decrease attributing to the photo-induced
      electron transfer process from the electrostatically attached CAP to the BSA
      AuNCs. The effects of pH, amount of BSA-AuNCs, temperature and reaction time on
      the detection of chloramphenicol were investigated. Under the optimal conditions,
      trace amounts of CAP could be detected. The linear working range is 0.10-70.00
      MUM with a detection limit 33 nM (S/N=3). In addition, the proposed method has
      been successfully applied to the detection of CAP in milk samples and largely
      improves the application of spectral method for quantitative analysis of CAP.

PMID- 25985128
TI  - Structural, optical and photocatalytic properties of Fe and (Co, Fe) co-doped
      copper oxide spin coated films.
AB  - Copper oxide films with composition Cu1-x-yFexCoyO (where x?0.06 and y?0.03 in a
      molar ratio) and thickness of about 2 MUm were spin coated onto ultrasonically
      cleaned glass substrates. These films were annealed at 500  degrees C in the air.
      XRD results show that films are CuO of polycrystalline and monoclinic structures
      without the detection of any Fe or Co traces. The average crystallite size of
      pure CuO is 20.44 nm reduced to 18.72 nm after Fe doping, then increased to 26.82
      nm due to the co-doping with Co atoms. The optical band gap blue-shifted from
      2.15 eV to 2.3 eV followed by red-shift to 2.15 eV after the Co incorporation.
      The influence of Fe doping and Co co-doping on the optical constants of CuO films
      as well as the photocatalytic removal of methylene blue (MB) dye is reported. The
      correlations between the structural modifications and the resultant optical
      properties are discussed. The obtained results of the fabricated system are
      compared with those of similar materials.

PMID- 25985127
TI  - Binding interaction of sorafenib with bovine serum albumin: Spectroscopic
      methodologies and molecular docking.
AB  - The binding interaction of sorafenib with bovine serum albumin (BSA) was studied
      using fluorescence, circular dichrosim (CD) and molecular docking methods. The
      results revealed that there was a static quenching of BSA induced by sorafenib
      due to the formation of sorafenib-BSA complex. The binding constant and number of
      binding site of sorafenib with BSA under simulated physiological condition
      (pH=7.4) were 6.8*10(4) M(-1) and 1 at 310 K, respectively. Base on the sign and
      magnitude of the enthalpy and entropy changes (DeltaH(0)=-72.2 kJ mol(-1) and
      DeltaS(0)=-140.4J mol(-1) K(-1)) and the results of molecular docking, it could
      be suggested that the binding process of sorafenib and BSA was spontaneous and
      the main interaction forces of sorafenib with BSA were van der Waals force and
      hydrogen bonding interaction. From the results of site marker competitive
      experiments and molecular docking, it could be deduced that sorafenib was
      inserted into the subdomain IIA (site I) of BSA and leads to a slight change of
      the conformation of BSA. And, the significant change of conformation of sorafenib
      occurred in the binding process with BSA to increase the stability of the
      sorafenib-BSA system, implying that the flexibility of sorafenib played an
      important role in the binding process.

PMID- 25985129
TI  - Monitoring potential molecular interactions of adenine with other amino acids
      using Raman spectroscopy and DFT modeling.
AB  - We report on the modes of inter-molecular interaction between adenine (Ade) and
      the amino acids: glycine (Gly), lysine (Lys) and arginine (Arg) using Raman
      spectroscopy of binary mixtures of adenine and each of the three amino acids at
      varying molar ratios in the spectral region 1550-550 cm(-1). We focused our
      attention on certain specific changes in the Raman bands of adenine arising due
      to its interaction with the amino acids. While the changes are less apparent in
      the Ade/Gly system, in the Ade/Lys or Ade/Arg systems, significant changes are
      observed, particularly in the Ade Raman bands that involve the amino group moiety
      and the N7 and N1 atoms of the purine ring. The nu(N1-C6), nu(N1-C2), delta(C8-H)
      and delta(N7-C8-N9) vibrations at 1486, 1332, 1253 and 948 cm(-1) show spectral
      changes on varying the Ade to amino acid molar ratio, the extent of variation
      being different for the three amino acids. This observation suggests a specific
      interaction mode between Ade and Lys or Arg, which is due to the hydrogen
      bonding. The measured spectral changes provide a clear indication that the
      interaction of Ade depends strongly on the structures of the amino acids,
      especially their side chains. Density functional theory (DFT) calculations were
      carried out to elucidate the most probable interaction modes of Ade with the
      different amino acids.

PMID- 25985130
TI  - A simplified FTIR chemometric method for simultaneous determination of four
      oxidation parameters of frying canola oil.
AB  - Transmission Fourier transform infrared (FTIR) spectroscopic method using 100 MUm
      KCl cell was applied for the determination of total polar compounds (TPC),
      carbonyl value (CV), conjugated diene (CD) and conjugated triene (CT) in canola
      oil (CLO) during potato chips frying at 180  degrees C. The calibration models
      were developed for TPC, CV, CD and CT using partial least square (PLS)
      chemometric technique. Excellent regression coefficients (R(2)) and root mean
      square error of prediction values for TPC, CV, CD and CT were found to be 0.999,
      0.992, 0.998 and 0.999 and 0.809, 0.690, 1.26 and 0.735, respectively. The
      developed calibration models were applied on samples of canola oil drawn during
      potato chips frying process. A linear relationship was obtained between CD and
      TPC with a good correlation of coefficient (R(2)=0.9816). Results of the study
      clearly indicated that transmission FTIR-PLS method could be used for quick and
      precise evaluation of oxidative changes during the frying process without using
      any organic solvent.

PMID- 25985131
TI  - Determination of copper (II) in foodstuffs based on its quenching effect on the
      fluorescence of N,N'-bis(pyridoxal phosphate)-o-phenylenediamine.
AB  - A Schiff base-type fluorescence probe was prepared for the detection of copper
      (II) in foodstuffs. The probe is N,N'-bis(pyridoxal phosphate)-o-phenylenediamine
      (BPPP). It was synthesized by utilizing the Schiff base condensation reaction of
      pyridoxal 5-phosphate with 1,2-phenylenediamine. BPPP has the properties of high
      fluorescence stability, good water solubility and low toxicity. Its maximum
      excitation wavelength and maximum fluorescence emission wavelength are at 389 and
      448 nm, respectively. When BPPP coexists with copper (II), its fluorescence is
      dramatically quenched. Under a certain condition, the fluorescence intensity
      decreased proportionally to the concentration of copper (II) by the quenching
      effect. Based on this fact, we established a fluorescence quenching method for
      the determination of copper (II). Under optimal conditions a linear range was
      found to be 0.5-50 ng/mL with a detection limit of 0.2 ng/mL. The method has been
      applied to determine copper (II) in foodstuff samples and the analytical results
      show good agreement with that obtained from atomic absorption spectrometry
      method.

PMID- 25985132
TI  - Characterization of the interaction of FTO protein with thioglycolic acid capped
      CdTe quantum dots and its analytical application.
AB  - CdTe quantum dots (QDs) were synthesized in aqueous solution using thioglycolic
      acid (TGA) as stabilizing agents. The interaction between TGA-CdTe QDs and fat
      mass and obesity-associated (FTO) protein was investigated by fluorescence, UV
      visible absorption, synchronous fluorescence and three-dimensional fluorescence
      spectroscopy. Results revealed that TGA-CdTe QDs could strongly quench the
      intrinsic fluorescence of FTO protein with a static quenching procedure. Both the
      van der Waals and hydrogen bonding played a major role in stabilizing the
      complex. The binding constant and thermodynamic parameters at different
      temperatures were obtained. In addition, we found that the fluorescence intensity
      of QDs was significantly enhanced by the addition of FTO protein. Based on this,
      a sensitive method for detecting FTO protein was obtained in the linear range of
      5.52*10(-9)-6.62*10(-7) mol L(-1) with the detection limit of 1.14*10(-9) mol L(
      1). The influences of factors on the interaction between FTO protein and TGA-CdTe
      QDs were studied.

PMID- 25985133
TI  - Fluorescence detection of Fe(3+) ions in aqueous solution and living cells based
      on a high selectivity and sensitivity chemosensor.
AB  - Although ferric ion (Fe(3+)) performs critical roles in diverse biochemical
      processes in living systems, its physiological and pathophysiological functions
      have not been fully explored due to the lack of methods for quantification of
      Fe(3+) ions in biological system. In this work, a highly sensitive and selective
      fluorescence chemosensor, L, was developed for the detection of Fe(3+) ions in
      aqueous solution and in living cells. L was facile synthesized by one step
      reaction and well characterized by NMR, API-ES, FT-IR, and elementary analysis.
      The prepared chemosensor displayed excellent selectivity for Fe(3+) ions
      detection over a wide range of tested metal ions. In the present of Fe(3+) ions,
      the strong green fluorescence of L was substantially quenched. The 1:1
      stoichiometry of the complexation was confirmed by a Job's plot. The association
      constant (Ka) of L with Fe(3+) was evaluated using the Benesi-Hildebrand method
      and was found to be 1.36*10(4) M(-1). The MTT assay determined that L exhibits
      low cytotoxicity toward living cells. Confocal imaging and flow cytometry studies
      showed that L is readily interiorized by MDA-MB-231 cells through an energy
      dependent pathway and could be used to detect of Fe(3+) ions in living cells.

PMID- 25985134
TI  - Luminescence and energy transfer of color-tunable Li6Gd(BO3)3:Ce(3+), Tb(3+)
      phosphor.
AB  - A series of novel color-tunable phosphors of Ce(3+), Tb(3+)-codoped Li6Gd(BO3)3
      was synthesized through a classic solid-state reaction. The color of these
      phosphors changes from blue to green by adjusting the ratio of Ce(3+) to Tb(3+).
      The photoluminescence properties of the synthesized phosphors were investigated,
      and several major emission bands that belong to Ce(3+) and Tb(3+) ions were
      irradiated with near ultraviolet light. Moreover, the energy transfer mechanism
      between Ce(3+) and Tb(3+) in Li6Gd(BO3)3 was explored. The photoluminescence
      decay curves were performed to validate the energy transfer. The analysis
      demonstrated that the energy transfer from Ce(3+) to Tb(3+) arose from dipole
      dipole interaction with a critical distance of approximately 17.6 A.

PMID- 25985135
TI  - Green synthesis of Y2O3:Dy(3+) nanophosphor with enhanced photocatalytic
      activity.
AB  - Facile and green route was employed for the synthesis of Y2O3:Dy(3+) (1-11 mol%)
      nanostructures (NSs) using Aloe vera gel as fuel. The formation of different
      morphologies of Y2O3:Dy(3+) NSs were characterized by SEM, TEM and HRTEM. PXRD
      data and Rietveld analysis evident the formation of single phase Y2O3 with cubic
      crystal structure. The influence of Dy(3+) ion concentration on the structure
      morphology, UV absorption, PL emission and photocatalytic activity of NSs were
      investigated. NSs exhibited an intense warm white emission with CIE chromaticity
      coordinates (0.32, 0.33) and average CCT value ~5525 K which corresponds to
      vertical day light. The control of Dy(3+) ion on Y2O3 matrix influences the
      photocatalytic decolorization of Metanil Yellow as a model compound was
      evaluated. The enhanced photocatalytic activities of core shell structured
      Y2O3:Dy(3+) (1 mol%) was attributed to co-operation effect of dopant
      concentration, crystallite size, textural properties and capability for reducing
      electron-hole pair recombination. Further, the recycling catalytic ability of
      Y2O3:Dy(3+) (1 mol%) nanostructure was also evaluated and found promising
      photocatalytic performance with negligible decrease in decolorization efficiency
      even after sixth successive cyclic runs. Considering its green, facile synthesis
      and recyclable feature from an aqueous solution, the present Y2O3:Dy(3+) (1 mol%)
      nanophosphor can be considered as one of the ideal photocatalyst for various
      potential applications.

PMID- 25985136
TI  - Concluding remarks.
AB  - Crystallization from solution is a crucial process used in the manufacture of a
      wide variety of materials. The first step in the crystallization process is the
      birth of a new crystalline phase, which is known as nucleation. Nucleation plays
      a key role in determining the results of any crystallization process with respect
      to the size, shape and crystal form obtained. Classical nucleation theory does
      not adequately explain the crystal nucleation process. Work described in the
      literature and at this Faraday Discussion describe more complex nucleation
      mechanisms which are generally known as two-step nucleation models. In addition,
      as most nucleation is influenced by dust, dirt and container surfaces, the
      importance of heterogeneous nucleation and the use of templates to accelerate
      nucleation and influence crystal form are promising methods for the study and
      control of nucleation. It is also clear from this Faraday Discussion that
      interest in this topic has grown, and new and novel experimental and modeling
      approaches are being used for the study of crystal nucleation from solution. 

PMID- 25985137
TI  - Meta-analysis of the heritability of human traits based on fifty years of twin
      studies.
AB  - Despite a century of research on complex traits in humans, the relative
      importance and specific nature of the influences of genes and environment on
      human traits remain controversial. We report a meta-analysis of twin correlations
      and reported variance components for 17,804 traits from 2,748 publications
      including 14,558,903 partly dependent twin pairs, virtually all published twin
      studies of complex traits. Estimates of heritability cluster strongly within
      functional domains, and across all traits the reported heritability is 49%. For a
      majority (69%) of traits, the observed twin correlations are consistent with a
      simple and parsimonious model where twin resemblance is solely due to additive
      genetic variation. The data are inconsistent with substantial influences from
      shared environment or non-additive genetic variation. This study provides the
      most comprehensive analysis of the causes of individual differences in human
      traits thus far and will guide future gene-mapping efforts. All the results can
      be visualized using the MaTCH webtool. 

PMID- 25985139
TI  - Genome-wide maps of recombination and chromosome segregation in human oocytes and
      embryos show selection for maternal recombination rates.
AB  - Crossover recombination reshuffles genes and prevents errors in segregation that
      lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of
      pregnancy failure and congenital disorders. Here we generate genome-wide maps of
      crossovers and chromosome segregation patterns by recovering all three products
      of single female meioses. Genotyping >4 million informative SNPs from 23 complete
      meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to
      infer the segregation patterns of 529 chromosome pairs. We uncover a new reverse
      chromosome segregation pattern in which both homologs separate their sister
      chromatids at meiosis I; detect selection for higher recombination rates in the
      female germ line by the elimination of aneuploid embryos; and report chromosomal
      drive against non-recombinant chromatids at meiosis II. Collectively, our
      findings show that recombination not only affects homolog segregation at meiosis
      I but also the fate of sister chromatids at meiosis II. 

PMID- 25985138
TI  - Factors influencing success of clinical genome sequencing across a broad spectrum
      of disorders.
AB  - To assess factors influencing the success of whole-genome sequencing for
      mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent
      cases or families across a broad spectrum of disorders in whom previous screening
      had identified no pathogenic variants. We quantified the number of candidate
      variants identified using different strategies for variant calling, filtering,
      annotation and prioritization. We found that jointly calling variants across
      samples, filtering against both local and external databases, deploying multiple
      annotation tools and using familial transmission above biological plausibility
      contributed to accuracy. Overall, we identified disease-causing variants in 21%
      of cases, with the proportion increasing to 34% (23/68) for mendelian disorders
      and 57% (8/14) in family trios. We also discovered 32 potentially clinically
      actionable variants in 18 genes unrelated to the referral disorder, although only
      4 were ultimately considered reportable. Our results demonstrate the value of
      genome sequencing for routine clinical diagnosis but also highlight many
      outstanding challenges. 

PMID- 25985140
TI  - Natural alleles of a proteasome alpha2 subunit gene contribute to thermotolerance
      and adaptation of African rice.
AB  - Global warming threatens many aspects of human life, for example, by reducing
      crop yields. Breeding heat-tolerant crops using genes conferring thermotolerance
      is a fundamental way to help deal with this challenge. Here we identify a major
      quantitative trait locus (QTL) for thermotolerance in African rice (Oryza
      glaberrima), Thermo-tolerance 1 (TT1), which encodes an alpha2 subunit of the 26S
      proteasome involved in the degradation of ubiquitinated proteins. Ubiquitylome
      analysis indicated that OgTT1 protects cells from heat stress through more
      efficient elimination of cytotoxic denatured proteins and more effective
      maintenance of heat-response processes than achieved with OsTT1. Variation in TT1
      has been selected for on the basis of climatic temperature and has had an
      important role in local adaptation during rice evolution. In addition, we found
      that overexpression of OgTT1 was associated with markedly enhanced
      thermotolerance in rice, Arabidopsis and Festuca elata. This discovery may lead
      to an increase in crop security in the face of the ongoing threat of global
      warming. 

PMID- 25985142
TI  - Systematic review of enriched enrolment, randomised withdrawal trial designs in
      chronic pain: a new framework for design and reporting.
AB  - Enriched enrolment, randomised withdrawal (EERW) pain trials select, before
      randomisation, patients who respond by demonstrating a predetermined degree of
      pain relief and acceptance of adverse events. There is uncertainty over the value
      of this design. We report a systematic review of EERW trials in chronic noncancer
      pain together with a critical appraisal of methods and potential biases in the
      methods used and recommendations for the design and reporting of future EERW
      trials. Electronic and other searches found 25 EERW trials published between 1995
      and June 2014, involving 5669 patients in a randomised withdrawal phase comparing
      drug with placebo; 13 (median, 107 patients) had a randomised withdrawal phase of
      6 weeks or less, and 12 (median, 334) lasted 12 to 26 weeks. Risks of bias
      included short duration, inadequate outcome definition, incomplete outcome data
      reporting, small size, and inadequate dose tapering on randomisation to placebo.
      Active treatment was usually better than placebo (22/25 trials). This review
      reduces the uncertainty around the value of EERW trials in pain. If properly
      designed, conducted, and reported, they are feasible and useful for making
      decisions about pain therapies. Shorter, small studies can be explanatory;
      longer, larger studies can inform practice. Current evidence is inadequate for
      valid comparisons in outcome between EERW and classical trials, although no gross
      differences were found. This systematic review provides a framework for assessing
      potential biases and the value of the EERW trials, and for the design of future
      studies by making recommendations for the conduct and reporting of EERW trials. 

PMID- 25985141
TI  - Genome-wide patterns and properties of de novo mutations in humans.
AB  - Mutations create variation in the population, fuel evolution and cause genetic
      diseases. Current knowledge about de novo mutations is incomplete and mostly
      indirect. Here we analyze 11,020 de novo mutations from the whole genomes of 250
      families. We show that de novo mutations in the offspring of older fathers are
      not only more numerous but also occur more frequently in early-replicating, genic
      regions. Functional regions exhibit higher mutation rates due to CpG
      dinucleotides and show signatures of transcription-coupled repair, whereas
      mutation clusters with a unique signature point to a new mutational mechanism.
      Mutation and recombination rates independently associate with nucleotide
      diversity, and regional variation in human-chimpanzee divergence is only partly
      explained by heterogeneity in mutation rate. Finally, we provide a genome-wide
      mutation rate map for medical and population genetics applications. Our results
      provide new insights and refine long-standing hypotheses about human mutagenesis.

PMID- 25985144
TI  - Folding Atomistic Proteins in Explicit Solvent Using Simulated Tempering.
AB  - Following a previous report on a coarse-grained protein model in implicit
      solvent, we applied simulated tempering (ST) with on-the-fly Helmholtz free
      energy (weight factors) determination to the folding or aggregation of seven
      proteins with the CHARMM, OPLS, and AMBER protein, and the SPC and TIP3P water
      force fields. For efficiency and reliability, we also performed replica exchange
      molecular dynamics (REMD) simulations on the alanine di- and deca-peptide, and
      the dimer of the Abeta16-22 Alzheimer's fragment, and used experimental data and
      previous simulation results on the chignolin, beta3s, Trp-cage, and WW domain
      peptides of 10-37 amino acids. The sampling with ST is found to be more efficient
      than with REMD for a much lower CPU cost. Starting from unfolded or extended
      conformations, the WW domain and the Trp-cage peptide fold to their NMR
      structures with a backbone RMSD of 2.0 and 1 A. Remarkably, the ST simulation
      explores transient non-native topologies for Trp-cage that have been rarely
      discussed by other simulations. Our ST simulations also show that the CHARMM22*
      force field has limitations in describing accurately the beta3s peptide. Taken
      together, these results open the door to the study of the configurations of
      single proteins, protein aggregates, and any molecular systems at atomic details
      in explicit solvent using a single normal CPU. They also demonstrate that our ST
      scheme can be used with any force field ranging from quantum mechanics to coarse
      grain and atomistic. 

PMID- 25985145
TI  - Adenosine and verapamil for no-reflow during primary percutaneous coronary
      intervention in people with acute myocardial infarction.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the preferred
      treatment for ST-segment elevation myocardial infarction. Although coronary flow
      is restored after PPCI, impaired myocardial perfusion (known as no-reflow)
      related to poor clinical outcomes is frequently observed. To overcome this
      phenomenon, drugs, such as atorvastatin, abciximab and others, have been tried as
      adjunctive treatment to PPCI. Among these drugs, verapamil and adenosine are
      among the most promising. No other systematic reviews have examined use of these
      two drugs in people with acute myocardial infarction (AMI) undergoing PPCI. This
      is an update of the version previously published (2013, Issue 6), for which the
      people of interest in the review were those treated with PPCI - not those given
      fibrinolytic therapy. OBJECTIVES: To study the impact of adenosine and verapamil
      on no-reflow during PPCI in people with AMI. SEARCH METHODS: We updated searches
      of the following databases in June 2014 without language restriction: the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of
      Science and BIOSIS, China National Knowledge Infrastructure and clinical trials
      registers (ClinicalTrials.gov, Current Controlled Trials, Australian and New
      Zealand Clinical Trials Registry, the World Health Organization (WHO)
      International Clinical Trials Registry Platform). We also handsearched The
      American Journal of Cardiology. SELECTION CRITERIA: We selected randomised
      controlled trials (RCTs) in which adenosine or verapamil was the primary
      intervention. Participants were individuals diagnosed with AMI who were
      undergoing PPCI. DATA COLLECTION AND ANALYSIS: Two review authors collected
      studies and extracted data. When necessary, we contacted trial authors to obtain
      relevant information. We calculated risk ratios (RRs), P values and 95%
      confidence intervals (CIs) of dichotomous data. MAIN RESULTS: We included in our
      review 11 RCTs (one new study with 59 participants) involving 1027 participants.
      Ten RCTs were associated with adenosine and one with verapamil. We considered the
      overall risk of bias of included studies to be moderate. We found no evidence
      that adenosine reduced short-term all-cause mortality (RR 0.61, 95% CI 0.25 to
      1.48, P value = 0.27), long-term all-cause mortality (RR 0.78, 95% CI 0.22 to
      2.74, P value = 0.70), short-term non-fatal myocardial infarction (RR 1.32, 95%
      0.33 to 5.29, P value = 0.69) or myocardial blush grade (MBG) 0 to 1 after PPCI
      (RR 0.96, 95% CI 0.76 to 1.22, P value = 0.75). The incidence of thrombolysis in
      myocardial infarction (TIMI) flow grade < 3 after PPCI (RR 0.62, 95% CI 0.42 to
      0.91, P value = 0.01) was decreased. Conversely, adverse events with adenosine,
      such as bradycardia (RR 6.32, 95% CI 2.98 to 13.41, P value < 0.00001),
      hypotension (RR 11.43, 95% CI 2.75 to 47.57, P value = 0.0008) and
      atrioventricular (AV) block (RR 6.78, 95% CI 2.15 to 21.38, P value = 0.001),
      were significantly increased.Meta-analysis of verapamil as treatment for no
      reflow during PPCI was not performed because data were insufficient. AUTHORS'
      CONCLUSIONS: It is difficult to draw conclusions because of the insufficient
      quality and quantity of current research studies. We considered the overall risk
      of bias of included studies to be moderate. Adenosine as treatment for no-reflow
      during PPCI could reduce angiographic no-reflow (TIMI flow grade < 3) but was
      found to increase adverse events. What's more, no evidence could be found to
      suggest that adenosine reduced all-cause mortality, non-fatal myocardial
      infarction or the incidence of myocardial blush grade 0 to 1. Additionally, the
      efficacy of verapamil for no-reflow during PPCI could not be analysed because
      data were insufficient. Further clinical research into adenosine and verapamil is
      needed because of the limited numbers of available trials and participants.

PMID- 25985143
TI  - The interplay between DNA repair and autophagy in cancer therapy.
AB  - DNA is the prime target of anticancer treatments. DNA damage triggers a series of
      signaling cascades promoting cellular survival, including DNA repair, cell cycle
      arrest, and autophagy. The elevated basal and/or stressful levels of both DNA
      repair and autophagy observed in tumor cells, in contrast to normal cells, have
      been identified as the most important drug-responsive programs that impact the
      outcome of anticancer therapy. The exact relationship between DNA repair and
      autophagy in cancer cells remains unclear. On one hand, autophagy has been shown
      to regulate some of the DNA repair proteins after DNA damage by maintaining the
      balance between their synthesis, stabilization, and degradation. One the other
      hand, some evidence has demonstrated that some DNA repair molecular have a
      crucial role in the initiation of autophagy. In this review, we mainly discuss
      the interplay between DNA repair and autophagy in anticancer therapy and expect
      to enlighten some effective strategies for cancer treatment. 

PMID- 25985146
TI  - Investigations of riboflavin photolysis via coloured light in the nitro blue
      tetrazolium assay for superoxide dismutase activity.
AB  - Determination of the superoxide dismutase activity is an important issue in the
      fields of biochemistry and the medical sciences. In the riboflavin/nitro blue
      tetrazolium (B2/NBT) method, the light sources used for generating superoxide
      anion radicals from light-excited riboflavin are normally fluorescent lamps.
      However, the conditions of B2/NBT experiments vary. This study investigated the
      effect of the light source on the light-excitation of riboflavin. The
      effectiveness of the photolysis was controlled by the wavelength of the light
      source. The spectra of fluorescent lamps are composed of multiple colour lights,
      and the emission spectra of fluorescent lamps made by different manufacturers may
      vary. Blue light was determined to be the most efficient for the photochemical
      reaction of riboflavin in visible region. The quality of the blue light in
      fluorescent lamps is critical to the photo-decomposition of riboflavin. A blue
      light is better than a fluorescent lamp for the photo-decomposition of
      riboflavin. The performance of the B2/NBT method is thereby optimized. 

PMID- 25985147
TI  - Probing the binding interaction of human serum albumin with three bioactive
      constituents of Eriobotrta japonica leaves: Spectroscopic and molecular modeling
      approaches.
AB  - Corosolic acid (CRA), maslinic acid (MA), and tormentic acid (TA) are three kind
      of bioactive constituents of Eriobotrta japonica leaves. In this study, plasma
      protein binding model prediction suggested that the binding ability to HSA was
      CRA>MA>TA. Furthermore, fluorescence spectroscopy confirmed this prediction. The
      results from emission and time resolved fluorescence studies revealed that the
      emission quenching of HSA with CRA, MA, and TA were all initiated by static
      quenching mechanism. From molecular docking results and site marker competitive
      experimental results it was possible to make good estimates about CRA, MA, and TA
      mainly bound to subdomain IIA of HSA. 3D fluorescence, FT-IR and CD spectra
      indicated that the local conformation of HSA molecules was affected by the
      presence of CRA, MA, and TA, but at different extents. 

PMID- 25985148
TI  - Improvement in UV protection retention capability and reduction in skin
      penetration of benzophenone-3 with mesoporous silica as drug carrier by
      encapsulation.
AB  - In this study, various amounts of benzophenone-3 (BP-3), a solid-type of organic
      UV-filter, were encapsulated in mesoporous silica (MS) to form the BP-3
      encapsulated by MS UV-filters (BESs), BES-1 and BES-2, via in-situ sol-gel
      process. The characterization of BESs was completed using Fourier transform
      infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and differential
      scanning calorimetry (DSC). The results showed that of the BES filters, BES-2
      containing emulsion (BES-2-E) exhibited about 2 times and 1.64 times higher SPF
      and erythemal UV-A PF values, respectively, and after 3 months about 7-8 times
      higher protection retention capability than the free BP-3 containing emulsion (BP
      3-E). Moreover, the result of the in vitro skin penetration test using Franz
      glass diffusion cell indicated that the skin permeation of BP-3 from BESs was
      about 3 times lower than from BP-3-E. This property is particularly important for
      sunscreens because the amount of sunscreen penetration inside the stratum corneum
      directly correlates to its UV protection ability, and consequently its ability to
      reduce phototoxic and photo-allergic reactions that are damaging to the skin. The
      results of this study demonstrated the potential of as-prepared BES-2 as a UV
      filter for cosmetic products.

PMID- 25985149
TI  - A Shared Decision-making Intervention: Success or Failure?

PMID- 25985150
TI  - In vitro properties of designed antimicrobial peptides that exhibit potent
      antipneumococcal activity and produces synergism in combination with penicillin.
AB  - Antimicrobial peptides (AMPs) represent a promising class of novel antimicrobial
      agents owing to their potent antimicrobial activity. In this study, two lead
      peptides from unrelated classes of AMPs were systematically hybridized into a
      series of five hybrid peptides (DM1-DM5) with conserved N- and C-termini. This
      approach allows sequence bridging of two highly dissimilar AMPs and enables
      sequence-activity relationship be detailed down to single amino acid level.
      Presence of specific amino acids and physicochemical properties were used to
      describe the antipneumococcal activity of these hybrids. Results obtained
      suggested that cell wall and/or membrane targeting could be the principal
      mechanism exerted by the hybrids leading to microbial cell killing. Moreover, the
      pneumocidal rate was greater than penicillin (PEN). Combination treatment with
      both DMs and PEN produced synergism. The hybrids were also broad spectrum against
      multiple common clinical bacteria. Sequence analysis showed that presence of
      specific residues has a major role in affecting the antimicrobial and cell
      toxicity of the hybrids than physicochemical properties. Future studies should
      continue to investigate the mechanisms of actions, in vivo therapeutic potential,
      and improve rational peptide design based on the current strategy.

PMID- 25985151
TI  - Structural changes in amorphous solid water films on heating to 120-140 K and 150
      160 K seen by positronium annihilation spectroscopy.
AB  - Changes in the structure of amorphous solid water films, grown by vapour
      deposition on a copper substrate at 75 K and then held at 120 K for 10 min to
      effect pore collapse, have been observed in the ranges 122-139 K and 150-162 K
      using positronium annihilation spectroscopy. It is proposed that the former is
      associated with the glass transition, with an effective activation energy of
      0.266(3) eV. The data for the latter, which exhibit minima suggesting the
      temporary introduction of molecular disorder, can be processed to yield an
      effective activation energy of 0.47(2) eV, and are consistent with either a
      structural reorganization of the crystalline lattice or a relaxation of the
      amorphous structure mediated by defect migration.

PMID- 25985153
TI  - Two-dimensional magnetic WS2@Fe3O4 nanocomposite with mesoporous silica coating
      for drug delivery and imaging-guided therapy of cancer.
AB  - Integrating multiple imaging and therapy functionalities into one single
      nanoscale platform has been proposed to be a promising strategy in cancer
      theranostics. In this work, WS2 nanosheets with their surface pre-adsorbed with
      iron oxide (IO) nanoparticles via self-assembly are coated with a mesoporous
      silica shell, on to which polyethylene glycol (PEG) is attached. The obtained WS2
      IO@MS-PEG composite nanoparticles exhibit many interesting inherent physical
      properties, including high near-infrared (NIR) light and X-ray absorbance, as
      well as strong superparamagnetism. In the mean time, the mesoporous silica shell
      in WS2-IO@MS-PEG could be loaded with a chemotherapy drug, doxorubicin (DOX),
      whose intracellular release afterwards may be triggered by NIR-induced
      photothermal heating for enhanced cancer cell killing. Upon systemic
      administration of such drug-loaded nano-theranostics, efficient tumor homing of
      WS2-IO@MS-PEG/DOX is observed in tumor-bearing mice as revealed by three-modal
      fluorescence, magnetic resonance (MR), and X-ray computed tomography (CT)
      imaging. In vivo combined photothermal & chemotherapy is then carried out with
      WS2-IO@MS-PEG/DOX, achieving a remarkably synergistic therapeutic effect superior
      to the respective mono-therapies. Our study highlights the promise of developing
      multifunctional nanoscale theranostics based on two-dimensional transition metal
      dichalcogenides (TMDCs) such as WS2 for multimodal imaging-guided combination
      therapy of cancer. 

PMID- 25985152
TI  - c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through
      modulation of the Wnt/Klf4 pathway.
AB  - The development of decellularised scaffolds for small diameter vascular grafts is
      hampered by their limited patency, due to the lack of luminal cell coverage by
      endothelial cells (EC) and to the low tone of the vessel due to absence of a
      contractile smooth muscle cells (SMC). In this study, we identify a population of
      vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived
      from immuno-privileged embryonic stem cells (ESCs). We also define an efficient
      and controlled differentiation protocol yielding fully to differentiated ECs and
      SMCs in sufficient numbers to allow the repopulation of a tissue engineered
      vascular graft. When seeded ex vivo on a decellularised vessel, c-Kit+/Sca-1
      derived cells recapitulated the native vessel structure and upon in vivo
      implantation in the mouse, markedly reduced neointima formation and mortality,
      restoring functional vascularisation. We showed that Kruppel-like transcription
      factor 4 (Klf4) regulates the choice of differentiation pathway of these cells
      through beta-catenin activation and was itself regulated by the canonical Wnt
      pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1
      cells can be differentiated through a Klf4/beta-catenin dependent pathway and are
      a suitable source of vascular progenitors for the creation of superior tissue
      engineered vessels from decellularised scaffolds. 

PMID- 25985154
TI  - Combinatorial approach for improving the outcome of angiogenic therapy in
      ischemic tissues.
AB  - Two major populations of endothelial progenitor cells (EPC), namely endothelial
      colony forming cells (ECFC, or late outgrowth EPC) and circulating angiogenic
      cells (CAC, or early outgrowth EPC) have been reported to play important roles in
      vasculogenesis in numerous pathological conditions. However, the poor retention
      of cells into the ischemic tissue and neovessel fragility are two major flaws
      that need to be overcome for successful angiogenic therapy. The objective of this
      study was to explore and exploit the functional properties of EPC populations in
      order to increase the effectiveness of post-ischemic cell therapy. The results
      indicate different, still complementary, effects of the two EPC populations on
      adherence and proliferation of vascular endothelial cells. Matrigel plug assay
      and mouse hind limb ischemia model showed that concomitant administration of CAC
      secreted factors and ECFC resulted in three-fold increase in local cell retention
      and improved muscle perfusion, vessel maturation and hind limb regeneration, in
      comparison to either treatment alone. By concluding, factors secreted by CAC co
      administered at the time of ECFC transplantation improve tissue regeneration and
      vascular repair through stabilization of newly-derived blood vessels. 

PMID- 25985156
TI  - Icariin protects against titanium particle-induced osteolysis and inflammatory
      response in a mouse calvarial model.
AB  - Periprosthetic osteolysis and subsequent aseptic loosening are common in implant
      failure, a complication with revision surgery being the only established
      treatment. Wear particle-induced inflammation and extensive osteoclastogenesis
      play critical roles in periprosthetic osteolysis. A recent approach in limiting
      osteolysis is therefore focused on inhibiting osteoclastic bone resorption. This
      study aimed to investigate the potential impact of icariin, the major ingredient
      of Epimedium, on titanium particle-induced osteolysis in a mouse calvarial model.
      Eighty-four male C57BL/J6 mice were divided randomly into four groups. Mice in
      the sham group underwent sham surgery only, whereas animals in the vehicle, low-
      and high-concentration icariin groups received titanium particles. Mice in the
      low- and high-concentration icariin groups were gavage-fed with icariin at 0.1 or
      0.3 mg/g/day, respectively, until sacrifice. Mice in the sham and vehicle groups
      received phosphate-buffered saline daily. After 2 weeks, mouse calvariae were
      collected for micro-computed tomography, histomorphometry and molecular analysis.
      Icariin significantly reduced particle-induced bone resorption compared with the
      vehicle group. Icariin also prevented an increase in receptor activator of
      nuclear factor kappa B ligand/osteoprotegerin ratio and subsequently suppressed
      osteoclast formation in titanium particle-charged calvariae. In addition,
      immunohistochemical analysis and enzyme-linked immunosorbent assay showed icariin
      significantly reduced expression and secretion of tumor necrosis factor-alpha,
      interleukin-1beta and interleukin-6 in the calvariae of titanium-stimulated mice.
      Collectively, these results suggest that icariin represents a potential treatment
      for titanium particle-induced osteolysis and could be developed as a new
      therapeutic candidate for the prevention and treatment of aseptic loosening.

PMID- 25985155
TI  - Physiologic force-frequency response in engineered heart muscle by
      electromechanical stimulation.
AB  - A hallmark of mature mammalian ventricular myocardium is a positive force
      frequency relationship (FFR). Despite evidence of organotypic structural and
      molecular maturation, a positive FFR has not been observed in mammalian tissue
      engineered heart muscle. We hypothesized that concurrent mechanical and
      electrical stimulation at frequencies matching physiological heart rate will
      result in functional maturation. We investigated the role of biomimetic
      mechanical and electrical stimulation in functional maturation in engineered
      heart muscle (EHM). Following tissue consolidation, EHM were subjected to
      electrical field stimulation at 0, 2, 4, or 6 Hz for 5 days, while strained on
      flexible poles to facilitate auxotonic contractions. EHM stimulated at 2 and 4 Hz
      displayed a similarly enhanced inotropic reserve, but a clearly diverging FFR.
      The positive FFR in 4 Hz stimulated EHM was associated with reduced calcium
      sensitivity, frequency-dependent acceleration of relaxation, and enhanced post
      rest potentiation. This was paralleled on the cellular level with improved
      calcium storage and release capacity of the sarcoplasmic reticulum and enhanced T
      tubulation. We conclude that electro-mechanical stimulation at a physiological
      frequency supports functional maturation in mammalian EHM. The observed positive
      FFR in EHM has important implications for the applicability of EHM in
      cardiovascular research. 

PMID- 25985157
TI  - MMP-2/9-Specific Activatable Lifetime Imaging Agent.
AB  - Optical (molecular) imaging can benefit from a combination of the high signal-to
      background ratio of activatable fluorescence imaging with the high specificity of
      luminescence lifetime imaging. To allow for this combination, both imaging
      techniques were integrated in a single imaging agent, a so-called activatable
      lifetime imaging agent. Important in the design of this imaging agent is the use
      of two luminophores that are tethered by a specific peptide with a hairpin-motive
      that ensured close proximity of the two while also having a specific amino acid
      sequence available for enzymatic cleavage by tumor-related MMP-2/9. Ir(ppy)3 and
      Cy5 were used because in close proximity the emission intensities of both
      luminophores were quenched and the influence of Cy5 shortens the Ir(ppy)3
      luminescence lifetime from 98 ns to 30 ns. Upon cleavage in vitro, both effects
      are undone, yielding an increase in Ir(ppy)3 and Cy5 luminescence and a
      restoration of Ir(ppy)3 luminescence lifetime to 94 ns. As a reference for the
      luminescence activation, a similar imaging agent with the more common Cy3-Cy5
      fluorophore pair was used. Our findings underline that the combination of
      enzymatic signal activation with lifetime imaging is possible and that it
      provides a promising method in the design of future disease specific imaging
      agents. 

PMID- 25985158
TI  - Assessing visual attention using eye tracking sensors in intelligent cognitive
      therapies based on serious games.
AB  - This study examines the use of eye tracking sensors as a means to identify
      children's behavior in attention-enhancement therapies. For this purpose, a set
      of data collected from 32 children with different attention skills is analyzed
      during their interaction with a set of puzzle games. The authors of this study
      hypothesize that participants with better performance may have quantifiably
      different eye-movement patterns from users with poorer results. The use of eye
      trackers outside the research community may help to extend their potential with
      available intelligent therapies, bringing state-of-the-art technologies to users.
      The use of gaze data constitutes a new information source in intelligent
      therapies that may help to build new approaches that are fully-customized to
      final users' needs. This may be achieved by implementing machine learning
      algorithms for classification. The initial study of the dataset has proven a 0.88
      (+/-0.11) classification accuracy with a random forest classifier, using cross
      validation and hierarchical tree-based feature selection. Further approaches need
      to be examined in order to establish more detailed attention behaviors and
      patterns among children with and without attention problems. 

PMID- 25985159
TI  - Free-Base Carboxyphenyl Porphyrin Films Using a TiO2 Columnar Matrix:
      Characterization and Application as NO2 Sensors.
AB  - The anchoring effect on free-base carboxyphenyl porphyrin films using TiO2
      microstructured columns as a host matrix and its influence on NO2 sensing have
      been studied in this work. Three porphyrins have been used: 5-(4
      carboxyphenyl)10,15,20-triphenyl-21H,23H-porphyrin (MCTPP); 5,10,15,20-tetrakis(4
      carboxyphenyl)-21H,23H-porphyrin (p-TCPP); and 5,10,15,20-tetrakis(3
      carboxyphenyl)-21H,23H-porphyrin (m-TCPP). The analysis of UV-Vis spectra of
      MCTPP/TiO2, p-TCPP/TiO2 and m-TCPP/TiO2 composite films has revealed that m
      TCPP/TiO2 films are the most stable, showing less aggregation than the other
      porphyrins. IR spectroscopy has shown that m-TCPP is bound to TiO2 through its
      four carboxylic acid groups, while p-TCPP is anchored by only one or two of these
      groups. MCTPP can only be bound by one carboxylic acid. Consequently, the binding
      of p-TCPP and MCTPP to the substrate allows them to form aggregates, whereas the
      more fixed anchoring of m-TCPP reduces this effect. The exposure of MCTPP/TiO2, p
      TCPP/TiO2 and m-TCPP/TiO2 films to NO2 has resulted in important changes in their
      UV-Vis spectra, revealing good sensing capabilities in all cases. The improved
      stability of films made with m-TCPP suggests this molecule as the best candidate
      among our set of porphyrins for the fabrication of NO2 sensors. Moreover, their
      concentration-dependent responses upon exposure to low concentrations of NO2
      confirm the potential of m-TCPP as a NO2 sensor. 

PMID- 25985160
TI  - Temperature-compensated force/pressure sensor based on multi-walled carbon
      nanotube epoxy composites.
AB  - In this study, we propose a multi-walled carbon nanotube epoxy composite sensor
      for force and pressure sensing in the range of 50 N-2 kN. A manufacturing
      procedure, including material preparation and deposition techniques, is proposed.
      The electrode dimensions and the layer thickness were optimized by the finite
      element method. Temperature compensation is realized by four nanocomposites
      elements, where only two elements are exposed to the measurand. In order to
      investigate the influence of the filler contents, samples with different
      compositions were prepared and investigated. Additionally, the specimens are
      characterized by cyclical and stepped force/pressure loads or at defined
      temperatures. The results show that the choice of the filler content should meet
      a compromise between sensitivity, temperature influence and noise behavior. At
      constant temperature, a force of at least 50N can be resolved. The measurement
      error due to the temperature influence is 150N in a temperature range of -20
      degrees C-50 degrees C. 

PMID- 25985161
TI  - Gait measurement system for the multi-target stepping task using a laser range
      sensor.
AB  - For the prevention of falling in the elderly, gait training has been proposed
      using tasks such as the multi-target stepping task (MTST), in which participants
      step on assigned colored targets. This study presents a gait measurement system
      using a laser range sensor for the MTST to evaluate the risk of falling. The
      system tracks both legs and measures general walking parameters such as stride
      length and walking speed. Additionally, it judges whether the participant steps
      on the assigned colored targets and detects cross steps to evaluate cognitive
      function. However, situations in which one leg is hidden from the sensor or the
      legs are close occur and are likely to lead to losing track of the legs or false
      tracking. To solve these problems, we propose a novel leg detection method with
      five observed leg patterns and global nearest neighbor-based data association
      with a variable validation region based on the state of each leg. In addition,
      methods to judge target steps and detect cross steps based on leg trajectory are
      proposed. From the experimental results with the elderly, it is confirmed that
      the proposed system can improve leg-tracking performance, judge target steps and
      detect cross steps with high accuracy. 

PMID- 25985162
TI  - Assessment of taste attributes of peanut meal enzymatic-hydrolysis hydrolysates
      using an electronic tongue.
AB  - Peanut meal is the byproduct of high-temperature peanut oil extraction; it is
      mainly composed of proteins, which have complex tastes after enzymatic hydrolysis
      to free amino acids and small peptides. The enzymatic hydrolysis method was
      adopted by using two compound proteases of trypsin and flavorzyme to hydrolyze
      peanut meal aiming to provide a flavor base. Hence, it is necessary to assess the
      taste attributes and assign definite taste scores of peanut meal double enzymatic
      hydrolysis hydrolysates (DEH). Conventionally, sensory analysis is used to assess
      taste intensity in DEH. However, it has disadvantages because it is expensive and
      laborious. Hence, in this study, both taste attributes and taste scores of peanut
      meal DEH were evaluated using an electronic tongue. In this regard, the response
      characteristics of the electronic tongue to the DEH samples and standard five
      taste samples were researched to qualitatively assess the taste attributes using
      PCA and DFA. PLS and RBF neural network (RBFNN) quantitative prediction models
      were employed to compare predictive abilities and to correlate results obtained
      from the electronic tongue and sensory analysis, respectively. The results showed
      that all prediction models had good correlations between the predicted scores
      from electronic tongue and those obtained from sensory analysis. The PLS and
      RBFNN prediction models constructed using the voltage response values from the
      sensors exhibited higher correlation and prediction ability than that of
      principal components. As compared with the taste performance by PLS model, that
      of RBFNN models was better. This study exhibits potential advantages and a
      concise objective taste assessment tool using the electronic tongue in the
      assessment of DEH taste attributes in the food industry. 

PMID- 25985163
TI  - Modification of an RBF ANN-Based Temperature Compensation Model of
      Interferometric Fiber Optical Gyroscopes.
AB  - This paper presents modification of Radial Basis Function Artificial Neural
      Network (RBF ANN)-based temperature compensation models for Interferometric Fiber
      Optical Gyroscopes (IFOGs). Based on the mathematical expression of IFOG output,
      three temperature relevant terms are extracted, which include: (1) temperature of
      fiber loops; (2) temperature variation of fiber loops; (3) temperature product
      term of fiber loops. Then, the input-modified RBF ANN-based temperature
      compensation scheme is established, in which temperature relevant terms are
      transferred to train the RBF ANN. Experimental temperature tests are conducted
      and sufficient data are collected and post-processed to form the novel RBF ANN.
      Finally, we apply the modified RBF ANN based on temperature compensation model in
      two IFOGs with temperature compensation capabilities. The experimental results
      show the proposed temperature compensation model could efficiently reduce the
      influence of environment temperature on the output of IFOG, and exhibit a better
      temperature compensation performance than conventional scheme without proposed
      improvements.

PMID- 25985164
TI  - Afocal optical flow sensor for reducing vertical height sensitivity in indoor
      robot localization and navigation.
AB  - This paper introduces a novel afocal optical flow sensor (OFS) system for
      odometry estimation in indoor robotic navigation. The OFS used in computer
      optical mouse has been adopted for mobile robots because it is not affected by
      wheel slippage. Vertical height variance is thought to be a dominant factor in
      systematic error when estimating moving distances in mobile robots driving on
      uneven surfaces. We propose an approach to mitigate this error by using an afocal
      (infinite effective focal length) system. We conducted experiments in a linear
      guide on carpet and three other materials with varying sensor heights from 30 to
      50 mm and a moving distance of 80 cm. The same experiments were repeated 10
      times. For the proposed afocal OFS module, a 1 mm change in sensor height induces
      a 0.1% systematic error; for comparison, the error for a conventional fixed-focal
      length OFS module is 14.7%. Finally, the proposed afocal OFS module was installed
      on a mobile robot and tested 10 times on a carpet for distances of 1 m. The
      average distance estimation error and standard deviation are 0.02% and 17.6%,
      respectively, whereas those for a conventional OFS module are 4.09% and 25.7%,
      respectively. 

PMID- 25985165
TI  - An adaptive compensation algorithm for temperature drift of micro-electro
      mechanical systems gyroscopes using a strong tracking Kalman filter.
AB  - We present an adaptive algorithm for a system integrated with micro-electro
      mechanical systems (MEMS) gyroscopes and a compass to eliminate the influence
      from the environment, compensate the temperature drift precisely, and improve the
      accuracy of the MEMS gyroscope. We use a simplified drift model and changing but
      appropriate model parameters to implement this algorithm. The model of MEMS
      gyroscope temperature drift is constructed mostly on the basis of the temperature
      sensitivity of the gyroscope. As the state variables of a strong tracking Kalman
      filter (STKF), the parameters of the temperature drift model can be calculated to
      adapt to the environment under the support of the compass. These parameters
      change intelligently with the environment to maintain the precision of the MEMS
      gyroscope in the changing temperature. The heading error is less than 0.6 degrees
      in the static temperature experiment, and also is kept in the range from 5
      degrees  to -2 degrees  in the dynamic outdoor experiment. This demonstrates that
      the proposed algorithm exhibits strong adaptability to a changing temperature,
      and performs significantly better than KF and MLR to compensate the temperature
      drift of a gyroscope and eliminate the influence of temperature variation. 

PMID- 25985166
TI  - NDIR Gas Sensor for Spatial Monitoring of Carbon Dioxide Concentrations in
      Naturally Ventilated Livestock Buildings.
AB  - The tracer gas ratio method, using CO2 as natural tracer, has been suggested as a
      pragmatic option to measure emissions from naturally ventilated (NV) barns
      without the need to directly estimate the ventilation rate. The aim of this
      research was to assess the performance of a low-cost Non-Dispersive Infra-Red
      (NDIR) sensor for intensive spatial field monitoring of CO2 concentrations in a
      NV dairy cow house. This was achieved by comparing NDIR sensors with two commonly
      applied methods, a Photo-Acoustic Spectroscope (PAS) Gas Monitor and an Open-Path
      laser (OP-laser). First, calibrations for the NDIR sensors were obtained in the
      laboratory. Then, the NDIR sensors were placed in a dairy cow barn for comparison
      with the PAS and OP-laser methods. The main conclusions were: (a) in order to
      represent the overall barn CO2 concentration of the dairy cow barn, the number of
      NDIR sensors to be accounted for average concentration calculation was dependent
      on barn length and on barn area occupation; and (b) the NDIR CO2 sensors are
      suitable for multi-point monitoring of CO2 concentrations in NV livestock barns,
      being a feasible alternative for the PAS and the OP-laser methods to monitor
      single-point or averaged spatial CO2 concentrations in livestock barns. 

PMID- 25985167
TI  - Estimation of joint forces and moments for the in-run and take-off in ski jumping
      based on measurements with wearable inertial sensors.
AB  - This study uses inertial sensors to measure ski jumper kinematics and joint
      dynamics, which was until now only a part of simulation studies. For subsequent
      calculation of dynamics in the joints, a link-segment model was developed. The
      model relies on the recursive Newton-Euler inverse dynamics. This approach
      allowed the calculation of the ground reaction force at take-off. For the model
      validation, four ski jumpers from the National Nordic center performed a
      simulated jump in a laboratory environment on a force platform; in total, 20
      jumps were recorded. The results fit well to the reference system, presenting
      small errors in the mean and standard deviation and small root-mean-square
      errors. The error is under 12% of the reference value. For field tests, six
      jumpers participated in the study; in total, 28 jumps were recorded. All of the
      measured forces and moments were within the range of prior simulated studies. The
      proposed system was able to indirectly provide the values of forces and moments
      in the joints of the ski-jumpers' body segments, as well as the ground reaction
      force during the in-run and take-off phases in comparison to the force platform
      installed on the table. Kinematics assessment and estimation of dynamics
      parameters can be applied to jumps from any ski jumping hill. 

PMID- 25985168
TI  - Precursor Routes to Complex Ternary Intermetallics: Single-Crystal and
      Microcrystalline Preparation of Clathrate-I Na8Al8Si38 from NaSi + NaAlSi.
AB  - Single crystals of the ternary clathrate-I Na8Al8Si38 were synthesized by
      kinetically controlled thermal decomposition (KCTD), and microcrystalline
      Na8Al8Si38 was synthesized by spark plasma sintering (SPS) using a NaSi + NaAlSi
      mixture as the precursor. Na8AlxSi46-x compositions with x <= 8 were also
      synthesized by SPS from precursor mixtures of different ratios. The crystal
      structure of Na8Al8Si38 was investigated using both Rietveld and single-crystal
      refinements. Temperature-dependent transport and UV/vis measurements were
      employed in the characterization of Na8Al8Si38, with diffuse-reflectance
      measurement indicating an indirect optical gap of 0.64 eV. Our results indicate
      that, when more than one precursor is used, both SPS and KCTD are effective
      methods for the synthesis of multinary inorganic phases that are not easily
      accessible by traditional solid-state synthesis or crystal growth techniques. 

PMID- 25985170
TI  - Determination of Mg(2+) Speciation in a TFSI(-)-Based Ionic Liquid With and
      Without Chelating Ethers Using Raman Spectroscopy.
AB  - Raman spectroscopy was employed to assess the complex environment of magnesium
      salts in the n-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide
      (BMPyrTFSI) room-temperature ionic liquid (RTIL). At room temperature, Mg(TFSI)2
      was miscible with BMPyrTFSI and formulated by [Mg(TFSI)2](x)[BMPyrTFSI](1-x) (x
      <= 0.55). Results suggest that at low concentrations of Mg(TFSI)2, anionic
      complexes in which Mg(2+) is surrounded by at least four TFSI(-) were formed.
      Above x = 0.2 an average of three TFSI(-) surround each Mg(2+). Below x = 0.12,
      there is a greater number of monodentate interactions between TFSI(-) oxygens and
      Mg(2+) cations, whereas above x = 0.12 bidentate ligands dominate. The fraction
      of TFSI(-) existing in the cis conformation increased with increasing Mg(2+)
      concentration. Mg(ClO4)2 was also studied as a Mg(2+) source. At equivalent mole
      fractions to those of the Mg(TFSI)2 salt, Mg(2+) from Mg(ClO4)2 was surrounded by
      only two TFSI(-) anions as ClO4(-) appeared to compete with TFSI(-) for
      coordination with Mg(2+). Similar behavior was also observed for the less soluble
      halide salts MgX2 (X = Cl, Br, I). Additions of chelating ligands were shown to
      effectively reduce the average number of TFSI(-) around Mg(2+) in a manner
      consistent with maintaining a sixfold oxygen coordination number around Mg(2+).
      Furthermore, an alternative class of ionic liquids, known as "solvate" ionic
      liquids, were produced. In this case glymes (Gm, m + 1 ether oxygens) were mixed
      with Mg(TFSI)2 so that glymes chelated Mg(2+), creating Mg(Gm)(y)(2+) complexes.
      The general formula was given by Mg(Gm)(y)(TFSI)2. These solvate ILs melt between
      40 and 80  degrees C. Raman spectra clearly showed the glyme chelating ability
      and stronger coordination with Mg(2+) with respect to TFSI(-). Finally, linear
      sweep voltammograms showed the anodic stability of the glymes to improve due to
      coordination with Mg(2+).

PMID- 25985171
TI  - Brain iron: a promising noninvasive biomarker of attention-deficit/hyperactivity
      disorder that warrants further investigation.

PMID- 25985169
TI  - Therapeutic hypothermia for the treatment of acute myocardial infarction-combined
      analysis of the RAPID MI-ICE and the CHILL-MI trials.
AB  - In the randomized rapid intravascular cooling in myocardial infarction as
      adjunctive to percutaneous coronary intervention (RAPID MI-ICE) and rapid
      endovascular catheter core cooling combined with cold saline as an adjunct to
      percutaneous coronary intervention for the treatment of acute myocardial
      infarction CHILL-MI studies, hypothermia was rapidly induced in conscious
      patients with ST-elevation myocardial infarction (STEMI) by a combination of cold
      saline and endovascular cooling. Twenty patients in RAPID MI-ICE and 120 in CHILL
      MI with large STEMIs, scheduled for primary percutaneous coronary intervention
      (PCI) within <6 hours after symptom onset were randomized to hypothermia induced
      by rapid infusion of 600-2000 mL cold saline combined with endovascular cooling
      or standard of care. Hypothermia was initiated before PCI and continued for 1-3
      hours after reperfusion aiming at a target temperature of 33 degrees C. The
      primary endpoint was myocardial infarct size (IS) as a percentage of myocardium
      at risk (IS/MaR) assessed by cardiac magnetic resonance imaging at 4+/-2 days.
      Patients randomized to hypothermia treatment achieved a mean core body
      temperature of 34.7 degrees C before reperfusion. Although significance was not
      achieved in CHILL-MI, in the pooled analysis IS/MaR was reduced in the
      hypothermia group, relative reduction (RR) 15% (40.5, 28.0-57.6 vs. 46.6, 36.8
      63.8, p=0.046, median, interquartile range [IQR]). IS/MaR was predominantly
      reduced in early anterior STEMI (0-4h) in the hypothermia group, RR=31% (40.5,
      28.8-51.9 vs. 59.0, 45.0-67.8, p=0.01, median, IQR). There was no mortality in
      either group. The incidence of heart failure was reduced in the hypothermia group
      (2 vs. 11, p=0.009). Patients with large MaR (>30% of the left ventricle)
      exhibited significantly reduced IS/MaR in the hypothermia group (40.5, 27.0-57.6
      vs. 55.1, 41.1-64.4, median, IQR; hypothermia n=42 vs. control n=37, p=0.03),
      while patients with MaR<30% did not show effect of hypothermia (35.8, 28.3-57.5
      vs. 38.4, 27.4-59.7, median, IQR; hypothermia n=15 vs. control n=19, p=0.50). The
      prespecified pooled analysis of RAPID MI-ICE and CHILL-MI indicates a reduction
      of myocardial IS and reduction in heart failure by 1-3 hours with endovascular
      cooling in association with primary PCI of acute STEMI predominantly in patients
      with large area of myocardium at risk. (ClinicalTrials.gov id NCT00417638 and
      NCT01379261).

PMID- 25985172
TI  - Association of estrogen measurements in serum and urine of premenopausal women.
AB  - AIMS: We evaluated conjugated and unconjugated urinary estrogen metabolites as
      surrogate biomarkers for serum levels of unconjugated E1 and E2 in premenopausal
      women. MATERIALS & METHODS: Repeated blood and urine samples were analyzed for
      estrogens and their metabolites using radioimmunoassays and liquid
      chromatography/mass spectrometry. RESULTS: The strongest correlation (r = 0.39)
      was observed between serum E1 and urinary E1 and E2. The correlations of urinary
      E2 (r = 0.35), E1 (r = 0.29), all E2 metabolites (r = 0.30), all E1 metabolites
      (r = 0.23) and total estrogens (r = 0.26) with serum E2 were only moderate
      although statistically significant. All correlations were substantially stronger
      for Whites than Asians. CONCLUSION: Urinary E2 emerged as the best predictor for
      serum E1 and E2, but the large intra-subject variability in urinary estrogen
      levels limits its use as a biomarker.

PMID- 25985173
TI  - Long-term stability of cancer biomarkers in human serum: biomarkers of oxidative
      stress and redox status, homocysteine, CRP and the enzymes ALT and GGT.
AB  - AIM: Five frequently used biomarkers in cancer research and epidemiological
      studies were tested for their assay stability upon storage of serum for 12 months
      at -20 and -70/-80 degrees C. MATERIALS & METHODS: The biomarker assays include
      reactive oxygen metabolites (ROM), the total thiol levels (TTL), homocysteine
      (HCy), C-reactive protein (HS-CRP) and two liver enzymes, alanine
      aminotransferase (ALT) and gamma-glutamyltransferase (GGT). RESULTS: The assays
      for ROM, HCy, HS-CRP and GGT were stable in human serum samples at the two
      temperatures tested. The two other assays TTL and ALT, however, showed
      statistically significant differences in their stability between -20 and -80
      degrees C. CONCLUSION: Therefore, storage at -80 degrees C is advised to maintain
      a reliable assay outcome when serum samples have to be stored for longer periods.

PMID- 25985174
TI  - Prognostic value of sST2 and galectin-3 for death relative to renal function in
      patients hospitalized for heart failure.
AB  - AIM: To evaluate the associations of soluble ST2 (sST2) and galectin-3 with death
      relative to renal function in patients with heart failure (HF). METHODS: Eleven
      hundred-and-sixty-one patients hospitalized for HF with 1-year follow up were
      enrolled for biomarkers analysis. RESULTS: Patients were divided into two groups
      based on eGFR of either > or <=60 ml/min/1.73 m(2). sST2 was independently
      associated with death in both categories of renal function, while galectin-3 lost
      this significance after addition of NT-proBNP to the model of patients with eGFR
      <=60 ml/min/1.73 m(2). CONCLUSION: In patients with HF, sST2 improved prediction
      for death beyond risk factors without being influenced by renal function,
      however, the prognostic value of galectin-3 is less clear below an eGFR of 60
      ml/min/1.73 m(2).

PMID- 25985175
TI  - Selected inflammatory markers in the diagnosis and monitoring of infections in
      children treated for hematological malignancies.
AB  - Infections in children treated for hematological malignancies pose a direct
      threat to life and are one of the most common causes of treatment failure in this
      group of patients. Unequivocal diagnosis at the early stages of infection
      together with an appropriate and timely treatment may be often difficult due to
      poor manifestation and nonspecific clinical symptoms of the infection progress.
      Inflammatory markers make a useful diagnostic tool for this purpose. They
      significantly help to diagnose, monitor, stratify and predict the outcome in
      severe infections. This article describes selected biomarkers, both those
      commonly used in clinical practice, such as erythrocyte sedimentation rate, C
      reactive protein, procalcitonin as well as less common like IL-6, IL-8 and
      moreover one promising novel marker - pentraxin 3. The authors emphasize their
      diagnostic value, clinical usefulness and significance in the treatment efficacy
      monitoring. 

PMID- 25985177
TI  - Transcriptomics: the key to biomarker discovery during tuberculosis?
AB  - Tuberculosis is a global threat affecting millions of people and requires more
      efficient methods of diagnosis, monitoring treatment response and the development
      of more efficacious drug therapies and new vaccines. The use of transcriptomic
      approaches and gene expression techniques have contributed to the elucidation of
      these aspects concerning the study of tuberculosis, and more specifically, the
      utilization of transcriptional profiles to identify biomarkers. These markers are
      the key to developing tools required to improve diagnosis and treatment of
      tuberculosis. Several studies have led to the identification of markers able to
      distinguish between different infection states, as well as other pulmonary
      diseases. Utilizing a systems biology approach will assist in obtaining more
      reliable results, leading to the implementation of significant findings. 

PMID- 25985176
TI  - The role of the tumor microenvironment in HIV-associated lymphomas.
AB  - There has been considerable interest in the role of the lymphoma
      microenvironment. Despite the use of highly active antiretroviral therapy
      (HAART), AIDS-related diffuse large-B-cell lymphoma remains common and HIV
      relatedHIV-associated classical Hodgkin's lymphoma is increasing in incidence.
      Less is known about the impact HIV and HAART have on the lymphoma
      microenvironment. AIDS-related diffuse large B-cell lymphoma is highly
      angiogenic, demonstrates increased lymphoblastic histology, proliferation,
      increased activated cytotoxic T cells, reduced CD4(+) and FOXP3(+) T cells, but
      no differences in tumor-associated macrophages. Early initiation of HAART
      improves immunosurveillance, but cases without viral antigens appear able to
      avoid immunologic reaction. Increased T cell infiltrates seen with HAART
      treatment in HIV-related classical Hodgkin's lymphoma may contribute to malignant
      cell growth. 

PMID- 25985178
TI  - Sexual selection protects against extinction.
AB  - Reproduction through sex carries substantial costs, mainly because only half of
      sexual adults produce offspring. It has been theorized that these costs could be
      countered if sex allows sexual selection to clear the universal fitness
      constraint of mutation load. Under sexual selection, competition between
      (usually) males and mate choice by (usually) females create important
      intraspecific filters for reproductive success, so that only a subset of males
      gains paternity. If reproductive success under sexual selection is dependent on
      individual condition, which is contingent to mutation load, then sexually
      selected filtering through 'genic capture' could offset the costs of sex because
      it provides genetic benefits to populations. Here we test this theory
      experimentally by comparing whether populations with histories of strong versus
      weak sexual selection purge mutation load and resist extinction differently.
      After evolving replicate populations of the flour beetle Tribolium castaneum for
      6 to 7 years under conditions that differed solely in the strengths of sexual
      selection, we revealed mutation load using inbreeding. Lineages from populations
      that had previously experienced strong sexual selection were resilient to
      extinction and maintained fitness under inbreeding, with some families continuing
      to survive after 20 generations of sib * sib mating. By contrast, lineages
      derived from populations that experienced weak or non-existent sexual selection
      showed rapid fitness declines under inbreeding, and all were extinct after
      generation 10. Multiple mutations across the genome with individually small
      effects can be difficult to clear, yet sum to a significant fitness load; our
      findings reveal that sexual selection reduces this load, improving population
      viability in the face of genetic stress. 

PMID- 25985181
TI  - Multiplexed Photoionization Mass Spectrometry Investigation of the O((3)P) +
      Propyne Reaction.
AB  - The reaction of O((3)P) + propyne (C3H4) was investigated at 298 K and 4 Torr
      using time-resolved multiplexed photoionization mass spectrometry and a
      synchrotron-generated tunable vacuum ultraviolet light source. The time-resolved
      mass spectra of the observed products suggest five major channels under our
      conditions: C2H3 + HCO, CH3 + HCCO, H + CH3CCO, C2H4 + CO, and C2H2 + H2 + CO.
      The relative branching ratios for these channels were found to be 1.00, (0.35 +/-
      0.11), (0.18 +/- 0.10), (0.73 +/- 0.27), and (1.31 +/- 0.62). In addition, we
      observed signals consistent with minor production of C3H3 + OH and H2 + CH2CCO,
      although we cannot conclusively assign them as direct product channels from
      O((3)P) + propyne. The direct abstraction mechanism plays only a minor role
      (<=1%), and we estimate that O((3)P) addition to the central carbon of propyne
      accounts for 10% of products, with addition to the terminal carbon accounting for
      the remaining 89%. The isotopologues observed in experiments using d1-propyne
      (CH3CCD) and analysis of product branching in light of previously computed
      stationary points on the singlet and triplet potential energy surfaces (PESs)
      relevant to O((3)P) + propyne suggest that, under our conditions, (84 +/- 14)% of
      the observed product channels from O((3)P) + propyne result from intersystem
      crossing from the initial triplet PES to the lower-lying singlet PES. 

PMID- 25985179
TI  - Structures of human phosphofructokinase-1 and atomic basis of cancer-associated
      mutations.
AB  - Phosphofructokinase-1 (PFK1), the 'gatekeeper' of glycolysis, catalyses the
      committed step of the glycolytic pathway by converting fructose-6-phosphate to
      fructose-1,6-bisphosphate. Allosteric activation and inhibition of PFK1 by over
      ten metabolites and in response to hormonal signalling fine-tune glycolytic flux
      to meet energy requirements. Mutations inhibiting PFK1 activity cause glycogen
      storage disease type VII, also known as Tarui disease, and mice deficient in
      muscle PFK1 have decreased fat stores. Additionally, PFK1 is proposed to have
      important roles in metabolic reprogramming in cancer. Despite its critical role
      in glucose flux, the biologically relevant crystal structure of the mammalian
      PFK1 tetramer has not been determined. Here we report the first structures of the
      mammalian PFK1 tetramer, for the human platelet isoform (PFKP), in complex with
      ATP-Mg(2+) and ADP at 3.1 and 3.4 A, respectively. The structures reveal
      substantial conformational changes in the enzyme upon nucleotide hydrolysis as
      well as a unique tetramer interface. Mutations of residues in this interface can
      affect tetramer formation, enzyme catalysis and regulation, indicating the
      functional importance of the tetramer. With altered glycolytic flux being a
      hallmark of cancers, these new structures allow a molecular understanding of the
      functional consequences of somatic PFK1 mutations identified in human cancers. We
      characterize three of these mutations and show they have distinct effects on
      allosteric regulation of PFKP activity and lactate production. The PFKP
      structural blueprint for somatic mutations as well as the catalytic site can
      guide therapeutic targeting of PFK1 activity to control dysregulated glycolysis
      in disease. 

PMID- 25985180
TI  - MET is required for the recruitment of anti-tumoural neutrophils.
AB  - Mutations or amplification of the MET proto-oncogene are involved in the
      pathogenesis of several tumours, which rely on the constitutive engagement of
      this pathway for their growth and survival. However, MET is expressed not only by
      cancer cells but also by tumour-associated stromal cells, although its precise
      role in this compartment is not well characterized. Here we show that MET is
      required for neutrophil chemoattraction and cytotoxicity in response to its
      ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances
      tumour growth and metastasis. This phenotype correlates with reduced neutrophil
      infiltration to both the primary tumour and metastatic sites. Similarly, Met is
      necessary for neutrophil transudation during colitis, skin rash or peritonitis.
      Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)
      alpha or other inflammatory stimuli in both mouse and human neutrophils. This
      induction is instrumental for neutrophil transmigration across an activated
      endothelium and for inducible nitric oxide synthase production upon HGF
      stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils
      promotes cancer cell killing, which abates tumour growth and metastasis. After
      systemic administration of a MET kinase inhibitor, we prove that the therapeutic
      benefit of MET targeting in cancer cells is partly countered by the pro-tumoural
      effect arising from MET blockade in neutrophils. Our work identifies an
      unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel'
      of MET-targeted therapies in cancer, and supports the rationale for evaluating
      anti-MET drugs in certain inflammatory diseases. 

PMID- 25985183
TI  - Water Vapor Sorption and Diffusion in Secondary Dispersion Barrier Coatings: A
      Critical Comparison with Emulsion Polymers.
AB  - The conventional method for synthesizing waterborne polymer colloids is emulsion
      polymerization using surfactants. An emerging method is the use of secondary
      dispersions (SD) of polymers in water, which avoids the addition of any
      surfactant. Although there are numerous studies of the water barrier properties
      (sorption, diffusion, and permeability) of waterborne emulsion (Em) polymer
      coatings, the properties of SD coatings, in comparison, have not been thoroughly
      investigated. Here, dynamic water vapor sorption analysis is used to compare the
      equilibrium sorption isotherms of the two forms of styrene-acrylate copolymers
      (Em and SD) with the same monomer composition. From an analysis of the kinetics
      of vapor sorption, the diffusion coefficient of water in the polymer coatings is
      determined. The combined effects of particle boundaries and surfactant addition
      were investigated through a comparison of the properties of SD and Em coatings to
      those of (1) solvent-cast polymer coatings (of the same monomer composition), (2)
      Em polymers that underwent dialysis to partially remove the water-soluble
      species, and (3) SD polymers with added surfactants. The results reveal that both
      the particle boundaries and the surfactants increase vapor sorption. The
      diffusion coefficients of water are comparable in magnitude in all of the polymer
      systems but are inversely related to water activity because of molecular
      clustering. Compared to all of the other waterborne polymer systems, the SD
      barrier coatings show the lowest equilibrium vapor sorption and permeability
      coefficients at high relative humidities as well as the lowest water diffusion
      coefficient at low humidities. These barrier properties make SD coatings an
      attractive alternative to conventional emulsion polymer coatings. 

PMID- 25985182
TI  - GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and
      Enhanced Insulin Sensitivity.
AB  - CONTEXT: Ecuadorian subjects with GH receptor deficiency (GHRD) have not
      developed diabetes, despite obesity. OBJECTIVE: We sought to determine the
      metabolic associations for this phenomenon. DESIGN: Four studies were carried
      out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation;
      3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance
      tests. SETTING: Clinical Research Institute in Quito, Ecuador. SUBJECTS: Adults
      homozygous for the E180 splice mutation of the GH receptor (GHRD) were matched
      for age, gender, and body mass index with unaffected control relatives (C) as
      follows: study 1, 27 GHRD and 35 C; study 2, 10 GHRD and 10 C; study 3, seven
      GHRD and 11 C; and study 4, seven GHRD and seven C. RESULTS: Although GHRD
      subjects had greater mean percentage body fat than controls, their fasting
      insulin, 2-hour blood glucose, and triglyceride levels were lower. The indicator
      of insulin sensitivity, homeostasis model of assessment 2%S, was greater (P <
      .0001), and the indicator of insulin resistance, homeostasis model of assessment
      2-IR, was lower (P = .0025). Metabolomic differences between GHRD and control
      subjects were consistent with their differing insulin sensitivity, including
      postprandial decreases of branched-chain amino acids that were more pronounced in
      controls. High molecular weight and total adiponectin concentrations were greater
      in GHRD (P = .0004 and P = .0128, respectively), and leptin levels were lower (P
      = .02). Although approximately 65% the weight of controls, GHRD subjects consumed
      an identical high-calorie meal; nonetheless, their mean glucose concentrations
      were lower, with mean insulin levels one-third those of controls. Results of the
      2-hour oral glucose tolerance test were similar. MAIN OUTCOME MEASURES: Measures
      of insulin sensitivity, adipocytokines, and energy metabolites. CONCLUSIONS:
      Without GH counter-regulation, GHRD is associated with insulin efficiency and
      obesity. Lower leptin levels, despite higher percentage body fat, suggest that
      obesity-associated leptin resistance is GH dependent. Elevated adiponectin levels
      not correlated with percentage body fat indicate that GH signaling is necessary
      for their typical suppression with obesity.

PMID- 25985184
TI  - The 100th anniversary of the four-point probe technique: the role of probe
      geometries in isotropic and anisotropic systems.
AB  - The electrical conductivity of solid-state matter is a fundamental physical
      property and can be precisely derived from the resistance measured via the four
      point probe technique excluding contributions from parasitic contact resistances.
      Over time, this method has become an interdisciplinary characterization tool in
      materials science, semiconductor industries, geology, physics, etc, and is
      employed for both fundamental and application-driven research. However, the
      correct derivation of the conductivity is a demanding task which faces several
      difficulties, e.g. the homogeneity of the sample or the isotropy of the phases.
      In addition, these sample-specific characteristics are intimately related to
      technical constraints such as the probe geometry and size of the sample. In
      particular, the latter is of importance for nanostructures which can now be
      probed technically on very small length scales. On the occasion of the 100th
      anniversary of the four-point probe technique, introduced by Frank Wenner, in
      this review we revisit and discuss various correction factors which are mandatory
      for an accurate derivation of the resistivity from the measured resistance. Among
      others, sample thickness, dimensionality, anisotropy, and the relative size and
      geometry of the sample with respect to the contact assembly are considered. We
      are also able to derive the correction factors for 2D anisotropic systems on
      circular finite areas with variable probe spacings. All these aspects are
      illustrated by state-of-the-art experiments carried out using a four-tip STM/SEM
      system. We are aware that this review article can only cover some of the most
      important topics. Regarding further aspects, e.g. technical realizations, the
      influence of inhomogeneities or different transport regimes, etc, we refer to
      other review articles in this field. 

PMID- 25985185
TI  - Research in Prehospital Care: Overcoming the Barriers to Success.
AB  - OBJECTIVE: The objective of this project was to determine how investigators
      conduct clinical trials in the prehospital setting and to suggest how emergency
      medical services (EMS) systems can develop the capacity to conduct prehospital
      clinical research. METHODS: A representative sample of U.S.-based study sites was
      selected from all studies registered on clinicaltrials.gov since the year 2000,
      where prehospital care providers conducted study-related activities in the
      prehospital setting. The site principal investigator and the research coordinator
      or EMS liaison were invited to participate in a structured discussion. A single
      interviewer conducted each discussion following a structured guide that
      generically asked for barriers and enablers to the sites' research success and
      then reviewed commonly identified prehospital research barriers. Notes were taken
      during each discussion and reviewed for common themes. Themes were reviewed by
      the project team and sent for comment to all participants. RESULTS: Discussions
      were held with 25 principal investigators, 9 coordinators, and 7 EMS liaisons. A
      total of 27 communities were represented in the discussions from 22 different
      states. The communities had a range of research experience from one prehospital
      trial to multiple trials. Key barriers were funding, ethics approval, data
      collection, protocol training and compliance, randomizing and blinding
      interventions, obtaining patient outcomes, adequate study staffing, and
      partnering with EMS agencies. CONCLUSION: This project identified many challenges
      to EMS research, but they were not insurmountable. Not every community can
      conduct every prehospital study. Communities should engage in studies that align
      with their values and resources. Investigators need to develop honest
      relationships where issues can be openly discussed and the community can
      collaborate on prehospital research. Learning from those who have overcome
      challenges may be a key to expanding the quality and quantity of EMS research.

PMID- 25985186
TI  - Reciprocal influence model of working alliance and therapeutic outcome over
      individual therapy course.
AB  - A reciprocal influence model of the working alliance and the therapeutic outcome
      was examined in a sample of clients (n = 638) seen by novice therapists. Past
      researchers have found a relation between the working alliance and symptom
      improvement and this relation has been interpreted as the alliance leading to
      such symptom change. The current study was an examination of whether the alliance
      does indeed lead to symptom change, or whether symptom change leads to subsequent
      alliance change, or whether each is related to the other in a reciprocal way over
      time. By modeling the longitudinal development of the working alliance and the
      symptomatic severity over the individual therapy course, we found support for the
      reciprocal model being superior to the unidirectional models. The ideas of
      relationship as strategy and relationship as outcome along with the reciprocal
      pattern revealed in the findings were discussed with respect to the theoretical
      and clinical implications. We also discussed the limitations of the study and
      provided suggestions for future research.

PMID- 25985187
TI  - Transitions in young adulthood: Exploring trajectories of parent-child conflict
      during college.
AB  - This longitudinal study examined trajectories of parent-child conflict from the
      perspective of young adults during their college years. Using group-based
      trajectory modeling, self-report data from 3 time points were analyzed and 4
      conflict trajectories emerged. The largest group of students (65%) had low,
      stable levels of parent-child conflict. Ten percent of the sample reported
      increases in parent-child conflict, and the remainder (25%) reported 1 of 2
      patterns of decreasing parent-child conflict. Students with at least 1 immigrant
      parent were more likely to experience changes in parent-child conflict in
      contrast to peers with no immigrant parents. Contrary to our hypotheses,
      individuals in the groups in which conflict was decreasing were more likely to
      experience psychological distress. Results are discussed in terms of implications
      for the heterogeneity of conflict trajectories over time, particularly
      considering the contextual influence of immigrant family status.

PMID- 25985188
TI  - Addressing Overuse of Medical Services One Decision at a Time.

PMID- 25985189
TI  - Assembling nonplanar polyaromatic units by click chemistry. Study of
      multicorannulene systems as host for fullerenes.
AB  - Novel compounds with two or three corannulene subunits have been obtained by
      "click chemistry". These exotic systems were synthesized in high yields using the
      ethynylcorannulene as common reagent. The synergistic action as receptors for
      fullerenes of several corannulene blocks has been evaluated. It was found that
      the three-armed derivatives showed efficient complexation abilities toward C60.
      Furthermore, a new compound having two corannulene subunits linked to a
      hexahelicene scaffold has a remarkable affinity constant. Finally, theoretical
      calculations have been performed to evaluate the formation of their relative
      adducts containing a C60 molecule. 

PMID- 25985191
TI  - On the electron vortex beam wavefunction within a crystal.
AB  - Electron vortex beams are distorted by scattering within a crystal, so that the
      wavefunction can effectively be decomposed into many vortex components. Using a
      Bloch wave approach equations are derived for vortex beam decomposition at any
      given depth and with respect to any frame of reference. In the kinematic limit
      (small specimen thickness) scattering largely takes place at the neighbouring
      atom columns with a local phase change of pi/2rad. When viewed along the beam
      propagation direction only one vortex component is present at the specimen
      entrance surface (i.e. the 'free space' vortex in vacuum), but at larger depths
      the probe is in a mixed state due to Bragg scattering. Simulations show that
      there is no direct correlation between vortex components and the <Lz>
      pendellosung, i.e. at a given depth probes with relatively constant <Lz> can be
      in a more mixed state compared to those with more rapidly varying <Lz>. This
      suggests that minimising oscillations in the <Lz> pendellosung by probe
      channelling is not the only criterion for generating a strong electron energy
      loss magnetic circular dichroism (EMCD) signal. 

PMID- 25985190
TI  - Basal protein phosphatase 2A activity restrains cytokine expression: role for
      MAPKs and tristetraprolin.
AB  - PP2A is a master controller of multiple inflammatory signaling pathways. It is a
      target in asthma; however the molecular mechanisms by which PP2A controls
      inflammation warrant further investigation. In A549 lung epithelial cells in
      vitro we show that inhibition of basal PP2A activity by okadaic acid (OA)
      releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic
      cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the
      anti-inflammatory protein - tristetraprolin (TTP), a destabilizing RNA binding
      protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition
      increases TTP mRNA expression, resultant TTP protein builds up in the
      hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro
      inflammatory cytokines increase and anti-inflammatory proteins are rendered
      inactive. Importantly, these effects can be reversed by the PP2A activators
      FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic
      subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression
      in cells stimulated with TNFalpha; as inhibition of PP2A with OA or PP2A-C siRNA
      results in significant increases in cytokine production. Collectively, these data
      reveal the molecular mechanisms of PP2A regulation and highlight the potential of
      boosting the power of endogenous phosphatases as novel anti-inflammatory
      strategies to combat asthmatic inflammation. 

PMID- 25985193
TI  - How did the media report on the Great East Japan Earthquake? Objectivity and
      emotionality seeking in Japanese media coverage.
AB  - The Great East Japan Earthquake was a tragic event requiring critical media
      involvement. Since the media played an important role in conveying factual
      information, journalists expressed feeling that it was difficult to guarantee the
      objectivity of their coverage. As media coverage constructs a socio-culturally
      shared reality among its audience, an examination of the objectivity and
      emotionality of the contents of the news coverage is needed. In Study 1, we
      conducted an exploratory content analysis of TV and newspaper coverage from the
      six month period following the March 11, 2011 disaster, finding that the news
      media generally reported neutral and objective factual information about the
      event, with emotionality shown only in the commentary. In order to examine how
      media coverage was constructed and evaluated by journalists, in Study 2 we
      conducted an online survey of 115 journalists working for mass media
      organizations. We found that that the journalists' orientations tended to be more
      objective than emotional, which is consistent with the findings of Study 1.
      However, their evaluations of the objectivity of the published articles were low,
      especially for the coverage of the nuclear power plant accident, which was an
      accident of an unprecedented nature. The negative emotions that journalists
      experienced during their investigations negatively affected subsequent
      evaluations of the objectivity of their reporting. 

PMID- 25985192
TI  - Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse
      Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent.
AB  - Abnormalities in the cerebrovascular system play a central role in many
      neurologic diseases. The on-going expansion of rodent models of human
      cerebrovascular diseases and the need to use these models to understand disease
      progression and treatment has amplified the need for reproducible non-invasive
      imaging methods for high-resolution visualization of the complete cerebral
      vasculature. In this study, we present methods for in vivo high-resolution (19
      MUm isotropic) computed tomography imaging of complete mouse brain vasculature.
      This technique enabled 3D visualization of large cerebrovascular networks,
      including the Circle of Willis. Blood vessels as small as 40 MUm were clearly
      delineated. ACTA2 mutations in humans cause cerebrovascular defects, including
      abnormally straightened arteries and a moyamoya-like arteriopathy characterized
      by bilateral narrowing of the internal carotid artery and stenosis of many large
      arteries. In vivo imaging studies performed in a mouse model of Acta2 mutations
      demonstrated the utility of this method for studying vascular morphometric
      changes that are practically impossible to identify using current histological
      methods. Specifically, the technique demonstrated changes in the width of the
      Circle of Willis, straightening of cerebral arteries and arterial stenoses. We
      believe the use of imaging methods described here will contribute substantially
      to the study of rodent cerebrovasculature.

PMID- 25985194
TI  - Exceptional Hydrophobicity of a Large-Pore Metal-Organic Zeolite.
AB  - Porous materials combining high hydrophobicity, large surface area, as well as
      large and uniform pore size are very useful but rare. The nanoporous zeolitic
      metal azolate framework, RHO-[Zn(eim)2] (MAF-6, Heim = 2-ethylimidazole), is an
      attractive candidate but thought to be unobtainable/unstable. In this work, the
      supramolecular isomerism of [Zn(eim)2] is thoroughly studied using a rapid
      solution mixing reaction of [Zn(NH3)4](OH)2 and Heim, which enables MAF-6 with
      high crystallinity, purity, and thermal/chemical stabilities to be synthesized in
      large quantity. Gas and vapor adsorption isotherms, gas chromatography, and water
      contact angle measurements, as well as transient breakthrough and molecular
      dynamics simulations show that MAF-6 exhibits large surface area (langmuir
      surface area 1695 m(2) g(-1)), pore volume (0.61 cm(3) g(-1)), pore size (d =
      18.4 A), and aperture size (d = 7.6 A) with high hydrophobicity on both the
      internal pore and external crystal surfaces. It can barely adsorb water or be
      wetted by water (contact angle 143 degrees ) but readily adsorb large amounts of
      organic molecules including methanol, ethanol, mesitylene, adamantane, C6-C10
      hydrocarbons, xylene isomers, and saturated/unsaturated analogues such as
      benzene/cyclohexene/cyclohexane or styrene/ethylbenzene. It can also separate
      these organic molecules from each other as well as from water by preferential
      adsorption/retention of those having higher hydrophobicity, lipophilicity, or
      oil/water partition coefficient. These properties are very different with other
      porous materials such as SOD-[Zn(mim)2] (Hmim = 2-methylimidazole, MAF-4/ZIF-8)
      with a hydrophobic pore surface but a hydrophilic crystal surface and small
      aperture size. 

PMID- 25985195
TI  - Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug
      Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin,
      Gallocatechin, and Dihydromyricetin Derivatives.
AB  - We are interested in developing novel natural product-derived P-gp inhibitors to
      reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of
      methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin
      (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51,
      and 53) are significantly better than epigallocatechin gallate (EGCG) with a
      relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50)
      of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to
      fibroblasts with IC50 > 100 MUM. Compound 23 is specific for P-gp without
      modulating activity toward MRP1 or BCRP. Compounds 23 and 51 are non-P-gp
      substrates. Important pharmacophores for P-gp modulation were identified. In
      summary, methylated EGC and GC derivatives represent a new class of potent,
      specific, noncytotoxic, and nonsubstrate P-gp modulators. 

PMID- 25985196
TI  - DNA-mediated gold nanoparticle signal transducers for combinatorial logic
      operations and heavy metal ions sensing.
AB  - Herein, the structure of two DNA strands which are complementary except fourteen
      T-T and C-C mismatches was programmed for the design of the combinatorial logic
      operation by utilizing the different protective capacities of single chain DNA,
      part-hybridized DNA and completed-hybridized DNA on unmodified gold
      nanoparticles. In the presence of either Hg(2+) or Ag(+), the T-Hg(2+)-T or C
      Ag(+)-C coordination chemistry could lead to the formation of part-hybridized DNA
      which keeps gold nanoparticles from clumping after the addition of 40 MUL 0.2M
      NaClO4 solution, but the protection would be screened by 120 MUL 0.2M NaClO4
      solution. While the coexistence of Hg(2+), Ag(+) caused the formation of
      completed-hybridized DNA and the protection for gold nanoparticles lost in either
      40 MUL or 120 MUL NaClO4 solutions. Benefiting from sharing of the same inputs of
      Hg(2+) and Ag(+), OR and AND logic gates were easily integrated into a simple
      colorimetric combinatorial logic operation in one system, which make it possible
      to execute logic gates in parallel to mimic arithmetic calculations on a binary
      digit. Furthermore, two other logic gates including INHIBIT1 and INHIBIT2 were
      realized to integrated with OR logic gate both for simultaneous qualitative
      discrimination and quantitative determination of Hg(2+) and Ag(+). Results
      indicate that the developed logic system based on the different protective
      capacities of DNA structure on gold nanoparticles provides a new pathway for the
      design of the combinatorial logic operation in one system and presents a useful
      strategy for development of advanced sensors, which may have potential
      applications in multiplex chemical analysis and molecular-scale computer design.

PMID- 25985197
TI  - Interface potential sensing from adsorption of human serum albumin (HSA) on
      carbon nanotube (CNT) monitored by zero current potentiometry for HSA
      determination.
AB  - In this work, the adsorption of human serum albumin (HSA) on the bare multiwall
      carbon nanotube (MWNT) was investigated by a new electrochemical method, termed
      as zero current potentiometry. For this, a MWNT strip was prepared by directly
      adhering MWNTs on the transparent adhesive tape surface. Moreover, when HSA
      adsorbed onto MWNT at the MWNT/solution interface, an interface potential Psi
      yielded. The interface potential Psi as the zero current potential Ezcp simply
      related to it was monitored by zero current potentiometry. The relationship
      between the zero current potential Ezcp, the HSA concentration and others was
      established in simple stoichiometric relation. Based on this, both the adsorption
      of HSA on MWNT and the HSA determination can be studied. For the HSA
      determination, the theoretic conclusion consisted with experimental results. The
      zero current potential Ezcp was proportional to the HSA concentration in the
      range of 2.8 * 10(-8) - 3.4 * 10(-7)M with the limit of detection 2 * 10(-8)M.
      The linear regression equation was Ezcp/V (vs, SCE) = (0.159 +/- 0.01) + (0.358
      +/- 0.02) * 10(6)CHSA (uM). This determination was fast, high sensitive and good
      selective.

PMID- 25985198
TI  - Fast and sensitive detection of an anthrax biomarker using SERS-based solenoid
      microfluidic sensor.
AB  - We report the application of a fully automated surface-enhanced Raman scattering
      (SERS)-based solenoid-embedded microfluidic device to the quantitative and
      sensitive detection of anthrax biomarker poly-gamma-D-glutamic acid (PGA) in
      solution. Analysis is based on the competitive reaction between PGA and PGA
      conjugated gold nanoparticles with anti-PGA-immobilized magnetic beads within a
      microfluidic environment. Magnetic immunocomplexes are trapped by yoke-type
      solenoids embedded within the device, and their SERS signals were directly
      measured and analyzed. To improve the accuracy of measurement process, external
      standard values for PGA-free serum were also measured through use of a control
      channel. This additional measurement greatly improves the reliability of the
      assay by minimizing the influence of extraneous experimental variables. The limit
      of detection (LOD) of PGA in serum, determined by our SERS-based microfluidic
      sensor, is estimated to be 100 pg/mL. We believe that the defined method
      represents a valuable analytical tool for the detection of anthrax-related
      aqueous samples.

PMID- 25985199
TI  - A simultaneous electrochemical multianalyte immunoassay of high sensitivity C
      reactive protein and soluble CD40 ligand based on reduced graphene oxide
      tetraethylene pentamine that directly adsorb metal ions as labels.
AB  - A simplified electrochemical multianalyte immunosensor for the simultaneous
      detection of high sensitivity C-reactive protein (hsCRP) and soluble CD40 ligand
      (sCD40L) that uses reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) that
      directly adsorbs metal ions as labels is reported. rGO-TEPA contains a large
      number of amino groups and has excellent conductivity, making it an ideal
      template for the loading of Pb(2+) and Cu(2+), which greatly amplifies the
      detection signals. The signals could be directly detected in a single run through
      differential pulse voltammetry (DPV), and each biorecognition event produces a
      distinct voltammetric peak. The position and size of each peak reflects the
      identity and the level of the corresponding antigen. Primarily designed for an
      application in a sandwich-type immunoassay based on Pb(2+) and Cu(2+) labels, two
      main challenges are accomplished with the herein presented nanosheets:
      fabrication of the template and the amination process for Pb(2+) and Cu(2+)
      adsorption. To further improve the analytical performance of the immunosensor,
      Au@bovine serum albumin (BSA) nanospheres synthesized through a "green" synthesis
      route were used as a sensor platform, which not only provides a biocompatible
      microenvironment for the immobilization of antibodies but also amplifies the
      electrochemical signals. Under optimal conditions, hsCRP and sCD40L could be
      assayed in the range of 0.05 to 100 ng mL(-1) with detection limits of 16.7 and
      13.1 pg mL(-1) (S/N=3), respectively. The assay results on clinical serum samples
      with the proposed immunosensor were in acceptable agreement with those using the
      standard single-analyte test of the enzyme-linked immunosorbent assay (ELISA).
      This novel immunosensing system provides a simple, sensitive and low-cost
      approach for a multianalyte immunoassay.

PMID- 25985200
TI  - Psychosocial Interventions for Problem Alcohol Use in Primary Care Settings
      (PINTA): Baseline Feasibility Data.
AB  - OBJECTIVE: Many individuals receiving methadone maintenance receive their
      treatment through their primary care provider. As many also drink alcohol
      excessively, there is a need to address alcohol use to improve health outcomes
      for these individuals. We examined problem alcohol use and its treatment among
      people attending primary care for methadone maintenance treatment, using baseline
      data from a feasibility study of an evidence-based complex intervention to
      improve care. METHODS: Data on addiction care processes were collected by (1)
      reviewing clinical records (n = 129) of people who attended 16 general practices
      for methadone maintenance treatment and (2) administering structured
      questionnaires to both patients (n = 106) and general practitioners (GPs) (n =
      15). RESULTS: Clinical records indicated that 24 patients (19%) were screened for
      problem alcohol use in the 12 months prior to data collection, with problem
      alcohol use identified in 14 (58% of those screened, 11% of the full sample). Of
      those who had positive screening results for problem alcohol use, five received a
      brief intervention by a GP and none were referred to specialist treatment. Scores
      on the Alcohol Use Disorders Identification Test (AUDIT) revealed the prevalence
      of hazardous, harmful, and dependent drinking to be 25% (n = 26), 6% (n = 6), and
      16% (n = 17), respectively. The intraclass correlation coefficient (ICC) for the
      proportion of patients with negative AUDITs was 0.038 (SE = 0.01). The ICCs for
      screening, brief intervention, and/or referral to treatment (SBIRT) were 0.16 (SE
      = 0.014), -0.06 (SE = 0.017), and 0.22 (SE = 0.026), respectively. Only 12
      (11.3%) AUDIT questionnaires concurred with corresponding clinical records that a
      patient had any/no problem alcohol use. Regular use of primary care was evident,
      as 25% had visited their GP more than 12 times during the past 3 months.
      CONCLUSIONS: Comparing clinical records with patients' experience of SBIRT can
      shed light on the process of care. Alcohol screening in people who attend primary
      care for substance use treatment is not routinely conducted. Interventions that
      enhance the care of problem alcohol use among this high-risk group are a
      priority.

PMID- 25985201
TI  - Factors influencing implementation of smoking cessation treatment within
      community mental health centers.
AB  - OBJECTIVE: Consumers with serious mental illness smoke more and are at higher
      risk for smoking-related illness. We examined provider and consumer factors
      influencing the implementation of the evidence-based "5 A's" (ask, advise,
      assess, assist, arrange) in six community mental health centers in greater
      Baltimore. METHODS: Data collected as part of a larger study examining the
      effectiveness of delivery of the 5 A's at patient visits. First, we examined
      responses to a survey administered to 49 clinicians on barriers and attitudes
      toward delivering the 5 A's. Second, we used multilevel models to examine
      variance between patients (n = 228), patient factors, and variance between their
      psychiatrists (n = 28) in the delivery of the 5 A's (and first 3 A's). RESULTS:
      The most strongly endorsed barrier was perceived lack of patient interest in
      smoking cessation. Psychiatrists and patients both accounted for significant
      variance in the delivery of the 5 A's and 3 A's. Patient "readiness to change"
      predicted delivery of the full 5 A's, while smoking severity predicted delivery
      of the first 3 A's. CONCLUSIONS: There is a critical need for creative and
      collaborative solutions, policies, and clinician training to address actual and
      perceived obstacles to the delivery of evidence-based smoking cessation treatment
      in the mental health care setting.

PMID- 25985202
TI  - Genome-Wide Analysis of the AP2/ERF Transcription Factors Family and the
      Expression Patterns of DREB Genes in Moso Bamboo (Phyllostachys edulis).
AB  - The AP2/ERF transcription factor family, one of the largest families unique to
      plants, performs a significant role in terms of regulation of growth and
      development, and responses to biotic and abiotic stresses. Moso bamboo
      (Phyllostachys edulis) is a fast-growing non-timber forest species with the
      highest ecological, economic and social values of all bamboos in Asia. The draft
      genome of moso bamboo and the available genomes of other plants provide great
      opportunities to research global information on the AP2/ERF family in moso
      bamboo. In total, 116 AP2/ERF transcription factors were identified in moso
      bamboo. The phylogeny analyses indicated that the 116 AP2/ERF genes could be
      divided into three subfamilies: AP2, RAV and ERF; and the ERF subfamily genes
      were divided into 11 groups. The gene structures, exons/introns and conserved
      motifs of the PeAP2/ERF genes were analyzed. Analysis of the evolutionary
      patterns and divergence showed the PeAP2/ERF genes underwent a large-scale event
      around 15 million years ago (MYA) and the division time of AP2/ERF family genes
      between rice and moso bamboo was 15-23 MYA. We surveyed the putative promoter
      regions of the PeDREBs and showed that largely stress-related cis-elements
      existed in these genes. Further analysis of expression patterns of PeDREBs
      revealed that the most were strongly induced by drought, low-temperature and/or
      high salinity stresses in roots and, in contrast, most PeDREB genes had negative
      functions in leaves under the same respective stresses. In this study there were
      two main interesting points: there were fewer members of the PeDREB subfamily in
      moso bamboo than in other plants and there were differences in DREB gene
      expression profiles between leaves and roots triggered in response to abiotic
      stress. The information produced from this study may be valuable in overcoming
      challenges in cultivating moso bamboo. 

PMID- 25985204
TI  - Urban-hazard risk analysis: mapping of heat-related risks in the elderly in major
      Italian cities.
AB  - BACKGROUND: Short-term impacts of high temperatures on the elderly are well
      known. Even though Italy has the highest proportion of elderly citizens in
      Europe, there is a lack of information on spatial heat-related elderly risks.
      OBJECTIVES: Development of high-resolution, heat-related urban risk maps
      regarding the elderly population (>= 65). METHODS: A long time-series (2001-2013)
      of remote sensing MODIS data, averaged over the summer period for eleven major
      Italian cities, were downscaled to obtain high spatial resolution (100 m) daytime
      and night-time land surface temperatures (LST). LST was estimated pixel-wise by
      applying two statistical model approaches: 1) the Linear Regression Model (LRM);
      2) the Generalized Additive Model (GAM). Total and elderly population density
      data were extracted from the Joint Research Centre population grid (100 m) from
      the 2001 census (Eurostat source), and processed together using "Crichton's Risk
      Triangle" hazard-risk methodology for obtaining a Heat-related Elderly Risk Index
      (HERI). RESULTS: The GAM procedure allowed for improved daytime and night-time
      LST estimations compared to the LRM approach. High-resolution maps of daytime and
      night-time HERI levels were developed for inland and coastal cities. Urban areas
      with the hazardous HERI level (very high risk) were not necessarily characterized
      by the highest temperatures. The hazardous HERI level was generally localized to
      encompass the city-centre in inland cities and the inner area in coastal cities.
      The two most dangerous HERI levels were greater in the coastal rather than inland
      cities. CONCLUSIONS: This study shows the great potential of combining geospatial
      technologies and spatial demographic characteristics within a simple and flexible
      framework in order to provide high-resolution urban mapping of daytime and night
      time HERI. In this way, potential areas for intervention are immediately
      identified with up-to-street level details. This information could support public
      health operators and facilitate coordination for heat-related emergencies.

PMID- 25985203
TI  - The Root Extract of Gentiana macrophylla Pall. Alleviates Cardiac Apoptosis in
      Lupus Prone Mice.
AB  - The roots of the perennial herb Gentiana macrophylla Pall. (GM) are known as
      Qinjiao, which has been used for centuries to treat systemic lupus erythematosus
      (SLE). However, little is known about the effects of GM on cholesterol-aggravated
      cardiac abnormalities in SLE, and the mechanisms thereof. This study investigates
      whether GM exhibits anti-apoptotic effects, focusing on the left ventricle (LV)
      of NZB/W F1 mice fed with high-cholesterol diet. The morphology and apoptotic
      status of ventricular tissues were determined by microscopy and Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Levels of
      apoptotic biomarkers were determined by immunoblotting. The results thus obtained
      revealed that GM significantly reduced the cholesterol-aggravated apoptosis of LV
      in NZB/W F1 mice by suppressing both intrinsic and extrinsic apoptotic pathways.
      Additionally, GM significantly increased the cardiac insulin-like growth factors
      (IGF)-1 survival signaling and anti-apoptotic proteins in LV tissues.
      Accordingly, GM is considered to be beneficial in alleviating cholesterol
      aggravated cardiac damage in SLE, and therefore constitute an alternative
      treatment for SLE patients with cardiac abnormalities. 

PMID- 25985205
TI  - Phylogeography of Nanorana parkeri (Anura: Ranidae) and multiple refugia on the
      Tibetan Plateau revealed by mitochondrial and nuclear DNA.
AB  - Quaternary climatic changes have been recognized to influence the distribution
      patterns and evolutionary histories of extant organisms, but their effects on
      alpine species are not well understood. To investigate the Pleistocene climatic
      oscillations on the genetic structure of amphibians, we sequenced one
      mitochondrial and three nuclear DNA fragments in Nanorana parkeri, a frog endemic
      to the Tibetan Plateau, across its distribution range in the southern plateau.
      Mitochondrial cytochrome b (Cytb) and three nuclear genes (c-Myc2, Rhod, and Tyr)
      revealed two distinct lineages (i.e. the lineages East and West), which were
      strongly geographically structured. The split of the two divergent lineages was
      dated back earlier than the Middle Pleistocene, probably being associated with
      climatic and ecological factors. Species distribution modeling, together with the
      phylogeographic structuring, supported the hypothesis of multiple refugia for N.
      parkeri on the Tibetan Plateau during the Pleistocene glaciations, and suggested
      the Yarlung Zangbo valley and the Kyichu catchment to be the potential refugia.
      Our findings indicate that Pleistocene climatic changes have had a great impact
      on the evolution and demographic history of N. parkeri. Our study has important
      implications for conservation of this and other frog species in the Tibetan
      Plateau. 

PMID- 25985206
TI  - Effect of heat-pressing temperature and holding time on the microstructure and
      flexural strength of lithium disilicate glass-ceramics.
AB  - The present study aimed to evaluate the influence of various heat-pressing
      procedures (different holding time and heat pressing temperature) on the
      microstructure and flexural strength of lithium disilicate glass ceramic. An
      experimental lithium silicate glass ceramic (ELDC) was prepared from the SiO2
      Li2O-K2O-Al2O3-ZrO2-P2O5 system and heat-pressed following different procedures
      by varying temperature and holding time. The flexural strength was tested and
      microstructure was analyzed. The relationships between the microstructure,
      mechanical properties and heat-pressing procedures were discussed in-depth.
      Results verified the feasibility of the application of dental heat-pressing
      technique in processing the experimental lithium disilicate glass ceramic.
      Different heat-pressing procedures showed significant influence on microstructure
      and flexural strength. ELDC heat-pressed at 950C with holding time of 15 min
      achieved an almost pore-free microstructure and the highest flexural strength,
      which was suitable for dental restorative application. 

PMID- 25985207
TI  - Photon small-field measurements with a CMOS active pixel sensor.
AB  - In this work the dosimetric performance of CMOS active pixel sensors for the
      measurement of small photon beams is presented. The detector used consisted of an
      array of 520  * 520 pixels on a 25 um pitch. Dosimetric parameters measured with
      this sensor were compared with data collected with an ionization chamber, a film
      detector and GEANT4 Monte Carlo simulations. The sensor performance for beam
      profiles measurements was evaluated for field sizes of 0.5  * 0.5 cm(2). The high
      spatial resolution achieved with this sensor allowed the accurate measurement of
      profiles, beam penumbrae and field size under lateral electronic disequilibrium.
      Field size and penumbrae agreed within 5.4% and 2.2% respectively with film
      measurements. Agreements with ionization chambers better than 1.0% were obtained
      when measuring tissue-phantom ratios. Output factor measurements were in good
      agreement with ionization chamber and Monte Carlo simulation. The data obtained
      from this imaging sensor can be easily analyzed to extract dosimetric
      information. The results presented in this work are promising for the development
      and implementation of CMOS active pixel sensors for dosimetry applications.

PMID- 25985208
TI  - Efficacy of corneal collagen cross-linking for treatment of keratoconus: a meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy of corneal collagen cross-linking (CXL) for
      the treatment of keratoconus. METHODS: We performed a literature search for
      randomized controlled trials that assessed the effect of CXL in slowing
      progression of keratoconus. The primary outcome measures included changes of
      topographic parameters, visual acuity, and refraction. Efficacy estimates were
      evaluated by weighted mean difference (WMD) and 95% confidence interval (CI) for
      absolute changes of the interested outcomes. RESULTS: Significant decrease in
      mean keratometry value, maximum keratometry value and minimum keratometry value
      were demonstrated in the CXL group compared with the control group (WMD = -1.65;
      95% CI: -2.51 to -0.80; P < 0.00001; WMD = -2.05; 95% CI: -3.10 to -1.00; P <
      0.00001; WMD = -1.94; 95% CI: -2.63 to -1.26; P < 0.00001; respectively). Best
      spectacle-corrected visual acuity improved significantly in CXL group (WMD = 
      0.10; 95% CI: -0.15 to -0.05; P < 0.00001), whereas uncorrected visual acuity did
      not differ statistically. Manifest cylinder error decreased significantly in
      patients undergoing CXL procedure compared with control patients in sensitivity
      analysis (WMD = -0.388; 95% CI: -0.757 to -0. 019; P = 0.04). The changes in
      central corneal thickness and intraocular pressure were not statistically
      significant. CONCLUSION: CXL may be an effective option in stabilizing
      keratoconus. Further long-term follow-up studies will be necessary to assess the
      persistence of CXL.

PMID- 25985209
TI  - Endothelial Caveolin-1 regulates the radiation response of epithelial prostate
      tumors.
AB  - The membrane protein caveolin-1 (Cav1) recently emerged as a novel oncogene
      involved in prostate cancer progression with opposed regulation in epithelial
      tumor cells and the tumor stroma. Here we examined the role of stromal Cav1 for
      growth and radiation response of MPR31-4 prostate cancer xenograft tumors using
      Cav1-deficient C57Bl/6 mice. Syngeneic MPR31-4 tumors grew faster when implanted
      into Cav1-deficient mice. Increased tumor growth on Cav1-deficient mice was
      linked to decreased integration of smooth muscle cells into the wall of newly
      formed blood vessels and thus with a less stabilized vessel phenotype compared
      with tumors from Cav1 wild-type animals. However, tumor growth delay of MPR31-4
      tumors grown on Cav1 knockout mice to a single high-dose irradiation with 20 Gray
      was more pronounced compared with tumors grown on wild-type mice. Increased
      radiation-induced tumor growth delay in Cav1-deficient mice was associated with
      an increased endothelial cell apoptosis. In vitro studies using cultured
      endothelial cells (ECs) confirmed that the loss of Cav1 expression increases
      sensitivity of ECs to radiation-induced apoptosis and reduces their clonogenic
      survival after irradiation. Immunohistochemical analysis of human tissue specimen
      further revealed that although Cav1 expression is mostly reduced in the tumor
      stroma of advanced and metastatic prostate cancer, the vascular compartment still
      expresses high levels of Cav1. In conclusion, the radiation response of MPR31-4
      prostate tumors is critically regulated by Cav1 expression in the tumor
      vasculature. Thus, Cav1 might be a promising therapeutic target for combinatorial
      therapies to counteract radiation resistance of prostate cancer at the level of
      the tumor vasculature. 

PMID- 25985211
TI  - Kinetics and Thermodynamics of the Reaction between the (*)OH Radical and
      Adenine: A Theoretical Investigation.
AB  - The accessibility of all possible reaction paths for the reaction between the
      nucleobase adenine and the (*)OH radical is investigated through quantum chemical
      calculations of barrier heights and rate constants at the omegaB97X-D/6
      311++G(2df,2pd) level with Eckart tunneling corrections. First the computational
      method is validated by considering the hydrogen abstraction from the heterocyclic
      N9 nitrogen in adenine as a test system. Geometries for all molecules in the
      reaction are optimized with four different DFT exchange-correlation functionals
      (B3LYP, BHandHLYP, M06-2X, and omegaB97X-D), in combination with Pople and
      Dunning basis sets, all of which have been employed in similar investigations in
      the literature. Improved energies are obtained through single point calculations
      with CCSD(T) and the same basis sets, and reaction rate constants are calculated
      for all methods both without tunneling corrections and with the Wigner, Bell, and
      Eckart corrections. In comparison to CCSD(T)//BHandHLYP/aug-cc-pVTZ reference
      results, the omegaB97X-D/6-311++G(2df,2pd) method combined with Eckart tunneling
      corrections provides a sensible compromise between accuracy and time. Using this
      method, all subreactions of the reaction between adenine and the (*)OH radical
      are investigated. The total rate constants for hydrogen abstraction and addition
      for adenine are predicted with this method to be 1.06 * 10(-12) and 1.10 * 10(
      12) cm(3) molecules(-1) s(-1), respectively. Abstractions of H61 and H62
      contribute the most, while only addition to the C8 carbon is found to be of any
      significance, in contrast to previous claims that addition is the dominant
      reaction pathway. The overall rate constant for the complete reaction is found to
      be 2.17 * 10(-12) cm(3) molecules(-1) s(-1), which agrees exceptionally well with
      experimental results. 

PMID- 25985210
TI  - The oncogenic role of the cochaperone Sgt1.
AB  - Sgt1/Sugt1, a cochaperone of Hsp90, is involved in several cellular activities
      including Cullin E3 ubiqutin ligase activity. The high level of Sgt1 expression
      in colorectal and gastric tumors suggests that Sgt1 is involved in tumorigenesis.
      Here, we report that Sgt1 is overexpressed in colon, breast and lung tumor
      tissues and in Ewing sarcoma and rhabdomyosarcoma xenografts. We also found that
      Sgt1 heterozygous knockout resulted in suppressed Hras-mediated transformation in
      vitro and tumor formation in p53(-/-) mouse embryonic fibroblast cells and
      significantly increased survival of p53(-/-) mice. Moreover, depletion of Sgt1
      inhibited the growth of Ewing sarcoma and rhabdomyosarcoma cells and destabilized
      EWS-FLI1 and PAX3-FOXO1 oncogenic fusion proteins, respectively, which are
      required for cellular growth. Our results suggest that Sgt1 contributes to cancer
      development by stabilizing oncoproteins and that Sgt1 is a potential therapeutic
      target. 

PMID- 25985212
TI  - Long-term exposure of the isopod Porcellionides pruinosus to nickel: Costs in the
      energy budget and detoxification enzymes.
AB  - Terrestrial isopods from the species Porcellionides pruinosus were exposed to the
      maximum allowed nickel concentration in the Canadian framework guideline (50 mg
      Ni/kg soil) and to 5* this concentration (250 mg Ni/kg soil). The exposure lasted
      for 28 days and was followed by a recovery period of 14 days where organisms were
      changed to clean soil. Organisms were sampled after 24 h, 48 h, 96 h, 7 days, 14
      days, 21 days, and 28 days of exposure, and at days 35 and 42 during the recovery
      period. For each sampling time the acetylcholinesterase (AChE), glutathione-S
      transferases (GST), catalase (CAT), lactate dehydrogenase (LDH) activities were
      determined as well as lipid peroxidation rate (LPO) along with lipids,
      carbohydrates, proteins content, energy available (Ea), energy consumption (Ec)
      and cellular energy allocation (CEA). The integrated biomarker response (IBR) was
      calculated for each sampling time as well as for each one of the above
      parameters. In addition, mortality was also recorded throughout the assay. The
      results obtained showed that nickel induced oxidative stress, evidenced by
      results on GST, GPx, CAT or LPO, but also on changes in the energy reserves
      content of these organisms. In addition, this study showed that these organisms
      possess a specific strategy to handle nickel toxicity. In this case, biomarkers
      were associated with costs in the energy budget, and the increase of energy
      reserves has a compensation for that cost.

PMID- 25985213
TI  - Assessment of radiological risk for marine biota and human consumers of seafood
      in the coast of Qingdao, China.
AB  - This paper reports the levels of (226)Ra, (232)Th, (40)K and (137)Cs in the
      edible parts of 11 different marine species collected from the Qingdao coast of
      China. The activities of (226)Ra, (232)Th and (40)K ranged from 0.08+/-0.03 to
      1.65+/-0.60 Bq kg(-1) w.w., 0.09+/-0.02 to 1.44+/-0.10 Bq kg(-1) w.w., 26.89+/
      1.25 to 219.25+/-5.61 Bq kg(-1) w.w., respectively. Artificial (137)Cs was
      undetectable or close to the detection limit in the biota sampled. To link
      radioactivity to possible impact on health, we calculated radiation doses to both
      the marine biota and human beings. We showed that doses in all cases were
      dominated by naturally occurring (40)K and that (137)Cs doses were negligible
      compared with (40)K-derived doses. The total doses to marine biota ranged between
      16.55 and 62.41 nGy h(-1) among different biota species, which were below the
      benchmark level of aquatic organism. The committed effective dose to humans
      through seafood consumption varied from 10.55 to 36.17 MUSv y(-1), and the
      associated lifetime cancer risks ranged from 5.93E-05 to 9.49E-05 for different
      age and gender groups. Both the dose and cancer risk to humans were at the
      acceptable range. Despite the significant amount of radionuclides released as a
      result of the Fukushima accident, their impact on the seafood in Qingdao coast
      appears to be negligible based on our measurements of concentrations of
      radionuclide activity and internal dose estimates.

PMID- 25985214
TI  - In vitro effects of thiamethoxam on larvae of Africanized honey bee Apis
      mellifera (Hymenoptera: Apidae).
AB  - Several investigations have revealed the toxic effects that neonicotinoids can
      have on Apis mellifera, while few studies have evaluated the impact of these
      insecticides can have on the larval stage of the honeybee. From the lethal
      concentration (LC50) of thiamethoxam for the larvae of the Africanized honeybee,
      we evaluated the sublethal effects of this insecticide on morphology of the
      brain. After determine the LC50 (14.34 ng/MUL of diet) of thiamethoxam, larvae
      were exposed to a sublethal concentration of thiamethoxam equivalent to 1.43
      ng/MUL by acute and subchronic exposure. Morphological and immunocytochemistry
      analysis of the brains of the exposed bees, showed condensed cells and early cell
      death in the optic lobes. Additional dose-related effects were observed on larval
      development. Our results show that the sublethal concentrations of thiamethoxam
      tested are toxic to Africanized honeybees larvae and can modulate the development
      and consequently could affect the maintenance and survival of the colony. These
      results represent the first assessment of the effects of thiamethoxam in
      Africanized honeybee larvae and should contribute to studies on honey bee colony
      decline.

PMID- 25985215
TI  - Hedgehog signaling inhibitors as anti-cancer agents in osteosarcoma.
AB  - Osteosarcoma is a rare type of cancer associated with a poor clinical outcome.
      Even though the pathologic characteristics of OS are well established, much
      remains to be understood, particularly at the molecular signaling level. The
      molecular mechanisms of osteosarcoma progression and metastases have not yet been
      fully elucidated and several evolutionary signaling pathways have been found to
      be linked with osteosarcoma pathogenesis, especially the hedgehog signaling (Hh)
      pathway. The present review will outline the importance and targeting the
      hedgehog signaling (Hh) pathway in osteosarcoma tumor biology. Available data
      also suggest that aberrant Hh signaling has pro-migratory effects and leads to
      the development of osteoblastic osteosarcoma. Activation of Hh signaling has been
      observed in osteosarcoma cell lines and also in primary human osteosarcoma
      specimens. Emerging data suggests that interference with Hh signal transduction
      by inhibitors may reduce osteosarcoma cell proliferation and tumor growth thereby
      preventing osteosarcomagenesis. From this perspective, we outline the current
      state of Hh pathway inhibitors in osteosarcoma. In summary, targeting Hh
      signaling by inhibitors promise to increase the efficacy of osteosarcoma
      treatment and improve patient outcome. 

PMID- 25985216
TI  - Association Between Cumulative Psychosocial Risk and Cervical Human
      Papillomavirus Infection Among Female Adolescents in a Free Vaccination Program.
AB  - OBJECTIVE: This study investigated the association of cervical human
      papillomavirus (HPV) infection with cumulative psychosocial risk reflecting
      family disadvantage, psychological distress, and unhealthy lifestyle. METHODS:
      The sample (N = 745) comprised sexually active female adolescent patients (12-19
      yr), primarily ethnic minorities, enrolled in a free HPV vaccination program.
      Subjects completed questionnaires and provided cervical swabs for HPV DNA
      testing. Unweighted and weighted principal component analyses for categorical
      data were used to derive multisystemic psychosocial risk indices using 9
      indicators: low socioeconomic status, lack of adult involvement, not attending
      high school/college, history of treatment for depression/anxiety,
      antisocial/delinquent behavior, number of recent sexual partners, use of alcohol,
      use of drugs, and dependency risk for alcohol/drugs. The association between
      cervical HPV (any type, high-risk types, vaccine types) assayed by polymerase
      chain reaction and self-reported number of psychosocial risk indicators was
      estimated using multivariable logistic regression. RESULTS: Subjects had a median
      of 3 psychosocial risk indicators. Multiple logistic regression analyses showed
      associations with unweighted and weighted number of psychosocial indicators for
      HPV any type (adjusted odds ratio [aOR] = 1.1; 95% confidence interval [CI], 1.0
      1.2), with the strongest associations between weighted drug/alcohol use,
      drug/alcohol dependency risk, and antisocial/delinquent behavior and detection of
      HPV vaccine types (aOR = 1.5; 95% CI, 1.1-2.0) independent of number of recent
      sexual partners and vaccine dose (0-3). CONCLUSION: Increased HPV infections
      including HPV vaccine types were associated with greater number of psychosocial
      risk indicators even after controlling for demographics, sexual behavior, history
      of chlamydia, and vaccine dose.

PMID- 25985217
TI  - Real-time particulate and CO concentrations from cookstoves in rural households
      in Udaipur, India.
AB  - Almost 3 billion people around the globe use traditional three-stone cookstoves
      and open fires to warm and feed themselves. The World Health Organization
      estimates annual mortality rates from domestic solid fuel combustion to be around
      4 million. One of the most affected countries is India. Quantifying pollutant
      concentrations from these cookstoves during different phases of operation and
      understanding the factors influencing their variability may help to identify
      where improvements should be targeted, enhancing indoor air quality for millions
      of the world's most vulnerable people. Gas and particulate measurements were
      collected between June and August, 2012, for 51 households using traditional
      cookstoves, in the villages of Udaipur district, Rajasthan, India. Mean pollutant
      concentrations during steady-state mode were 4989 MUm(2) cm(-3), 9835 MUg m(-3),
      and 18.5 ppm for lung-deposited surface area, PM2.5, and CO, respectively. Simple
      and multivariate regression analysis was conducted. Fuel amount, fuel diameter,
      duration of the cookstove run, roof-type, and the room dimension explained
      between 7% and 21% of the variability for the pollutant metrics. CO demonstrated
      weaker correlations with explanatory variables. Some of these variables may be
      indicative of socio-economic status and could be used as proxies of exposure in
      lieu of pollutant measurements, hence these variables may help identify which
      households to prioritize for intervention. Such associations should be further
      explored.

PMID- 25985218
TI  - Serum FGF21 levels are associated with brown adipose tissue activity in humans.
AB  - The obesity pandemic has spurred a need for novel therapies to prevent and treat
      metabolic complications. The recent rediscovery of brown adipose tissue (BAT) in
      humans made this tissue a possible therapeutic target, due to its potentially
      substantial contributions to energy homeostasis. Fibroblast growth factor 21
      (FGF21) has been identified as a facilitator of cold-induced thermogenesis in
      humans. Furthermore, pre-clinical studies revealed that FGF21 administration
      leads to improvement in the metabolic consequences of obesity, such as
      dyslipidemia and type 2 diabetes. Here we studied plasma FGF21 levels in two
      cohorts of human subjects, in whom BAT activity was determined using an
      individualized cooling protocol by [(18)F]FDG-PET/CT scan. Importantly, we found
      that circulating FGF21 levels correlated with BAT activity during acute cold
      exposure in male subjects. In addition, FGF21 levels were related to the change
      in core temperature upon acute cold exposure, indicating a role for FGF21 in
      maintaining normothermia, possibly via activation of BAT. Furthermore, cold
      acclimation increased BAT activity in parallel with increased FGF21 levels. In
      conclusion, our results demonstrate that FGF21 levels in humans are related to
      BAT activity, suggesting that FGF21 may represent a novel mechanism via which BAT
      activity in humans may be enhanced. 

PMID- 25985219
TI  - Performance of Wells Score for Deep Vein Thrombosis in the Inpatient Setting.
AB  - IMPORTANCE: The Wells score to determine the pretest probability of deep vein
      thrombosis (DVT) was validated in outpatient settings, but it is unclear whether
      it applies to inpatients. OBJECTIVE: To evaluate the utility of the Wells score
      for risk stratification of inpatients with suspected DVT. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective study was conducted in a 793-bed quaternary care,
      academic hospital using Wells score clinical predictor findings entered by health
      care professionals in a computerized physician order entry system at the time
      lower-extremity venous duplex ultrasound studies were ordered. All adult
      inpatients suspected of having lower-extremity DVT who underwent lower-extremity
      venous duplex ultrasound studies between November 1, 2012, and December 31, 2013,
      were included. Patients with DVT diagnosed within the prior 3 months were
      excluded. For patients undergoing multiple lower-extremity venous duplex
      ultrasound studies, only the first was included. MAIN OUTCOMES AND MEASURES: Our
      primary outcome was the Wells score's utility for risk stratification among
      inpatients with suspected DVT as measured by the difference in incidence of
      proximal DVT among the 3 Wells score categories (low, moderate, and high pretest
      probability), the discrimination accuracy of the Wells score categories as the
      area under the receiver operating characteristics curve, the failure rate of
      Wells score prediction, and the efficiency of the Wells score to exclude DVT.
      RESULTS: In a study cohort of 1135 inpatients, 137 (12.1%) had proximal DVT.
      Proximal DVT incidence in low, moderate, and high pretest probability groups was
      5.9% (8 of 135), 9.5% (48 of 506), and 16.4% (81 of 494), respectively (P <
      .001). The area under the receiver operating characteristics curve for the
      discriminatory accuracy of the Wells score for risk of proximal DVT identified on
      lower-extremity venous duplex ultrasound studies was 0.60. The failure rate of
      the Wells score to classify patients with a low pretest probability was 5.9% (95%
      CI, 3.0%-11.3%); the efficiency was 11.9% (95% CI, 10.1%-13.9%). CONCLUSIONS AND
      RELEVANCE: The Wells score performed only slightly better than chance for
      discrimination of risk for DVT in hospitalized patients. It had a higher failure
      rate and a lower efficiency in the inpatient setting compared with that reported
      in the outpatient literature. Therefore, the Wells score risk stratification is
      not sufficient to rule out DVT or influence management decisions in the inpatient
      setting.

PMID- 25985220
TI  - The Dual Characteristics of Light-Induced Cryptochrome 2, Homo-oligomerization
      and Heterodimerization, for Optogenetic Manipulation in Mammalian Cells.
AB  - The photoreceptor cryptochrome 2 (CRY2) has become a powerful optogenetic tool
      that allows light-inducible manipulation of various signaling pathways and
      cellular processes in mammalian cells with high spatiotemporal precision and ease
      of application. However, it has also been shown that the behavior of CRY2 under
      blue light is complex, as the photoexcited CRY2 can both undergo homo
      oligomerization and heterodimerization by binding to its dimerization partner
      CIB1. To better understand the light-induced CRY2 activities in mammalian cells,
      this article systematically characterizes CRY2 homo-oligomerization in different
      cellular compartments, as well as how CRY2 homo-oligomerization and
      heterodimerization activities affect each other. Quantitative analysis reveals
      that membrane-bound CRY2 has drastically enhanced oligomerization activity
      compared to that of its cytoplasmic form. While CRY2 homo-oligomerization and
      CRY2-CIB1 heterodimerization could happen concomitantly, the presence of certain
      CIB1 fusion proteins can suppress CRY2 homo-oligomerization. However, the homo
      oligomerization of cytoplasmic CRY2 can be significantly intensified by its
      recruitment to the membrane via interaction with the membrane-bound CIB1. These
      results contribute to the understanding of the light-inducible CRY2-CRY2 and CRY2
      CIB1 interaction systems and can be used as a guide to establish new strategies
      utilizing the dual optogenetic characteristics of CRY2 to probe cellular
      processes. 

PMID- 25985221
TI  - [The Motivation for Physicians in Training as Specialists in General Medicine to
      Open their Own Surgery].
AB  - Our mixed methods (narrative interviews; group discussions; quantitative online
      survey) study examines the motivation of physicians in training as specialists in
      general practice to open their own practice. In addition, we wondered how
      motivations change during the vocational training. In a synchronic perspective
      motivations are highly differentiated on the one hand, on the other hand they are
      clearly gender-specific. In a diachronic perspective, the decision for or against
      their own GP surgery is uncertain for a long time during vocational training.

PMID- 25985222
TI  - [Results of a Survey of Insurance Holders on Cure Regimes Performed in Foreign
      European Countries].
AB  - OBJECTIVE: The aim of this study was to investigate the reasons of the insured in
      Germany for taking cure regimes in foreign European countries. METHODS: Health
      insurances conducted a survey including insurance holders in Germany who had
      taken a cure regime in a foreign European country in 2012 or 2011. In a paper
      pencil interview, the sample was asked why they performed the cure regime abroad,
      how satisfied they were regarding the quality of the health professionals and the
      treatment, respectively, how long a positive effect lasted, where they spent
      their cure regime and about their plans regarding a future treatment in a health
      resort. RESULTS: In total, 443 insurance holders (60.7% female, mean age 68
      years) were included. Price-performance ratio of board, lodging and treatment
      (75.6%), the health resorts' reputation (64.5%) and recommendations of the
      personal environment (56.1%) were the main reasons for taking a cure regime
      abroad. Most of the participants were satisfied with the quality of the health
      professionals and the health resort; two thirds rated the effect as lasting
      longer than 3 months. The study population predominantly took services of health
      resorts located in the Czech Republic, in Hungary and in Poland. For taking a
      cure in the future, most of the study participants (77%) preferred health resorts
      abroad, however, a gender-specific analysis revealed this trend to be more
      pronounced in the male study population. CONCLUSION: Based on the results of the
      survey one might suggest that cost factors along with high level of satisfaction
      regarding the quality of treatments provided at the health resorts abroad,
      positively influence the decision for taking a cure regime in a foreign country.
      In the sample of this study, the decision is rarely based on the health
      insurances' or the health resorts' promotion activity, respectively. However, to
      conclude on the total population, requires data of a representative sample.

PMID- 25985223
TI  - [Families with Migrant Backgrounds as Target Group of Early Interventions:
      Results of a Social Early Warning System in a Metropolitan Region].
AB  - OBJECTIVES: Families with migrant backgrounds (MB) are exposed to several
      psychosocial risk factors that increase the likelihood of impaired child
      development, in particular. QUESTIONS: We investigated whether families with MB
      differ from families without MB regarding their psychosocial stressors in the
      period of pregnancy and birth. METHOD: As part of a social early warning system
      in an obstetrics clinic in Germany n=502 families with MB were compared with
      n=349 families without MB with respect to the degree of stress and stress factors
      on the basis of an initial screening of risk factors for child maltreatment by a
      midwife or physician and a subsequent structured clearing interview by social
      education workers during the mothers' inpatient hospitalisation. RESULTS: For
      families without MB, a significantly higher total score was found in the risk
      screening (M=3,9 points vs. M=2,9 points) in comparison to families with MB.
      While families with MB compared to families without MB were faced more frequently
      by social stressors, e. g., financial problems or a difficult housing situation
      (81 vs. 37%), they were less frequently impacted by mental strain (27 vs. 48%),
      young fathers (2 vs. 10%) and maternal psychiatric diseases (3 vs. 17%),
      according to the risk screening. Socio-economic determinants such as social
      inclusion and living environment were found to be important factors influencing
      the psychosocial stress level of families. CONCLUSION: Explanations and
      implications for research and practice are discussed.

PMID- 25985224
TI  - [Cost and Income Analysis of the 10 Most Frequent Angiography Interventions at a
      German University Hospital].
AB  - Aim: Our aim was to make a detailed evaluation and cost analysis of the 10 most
      frequent angiography interventions in outpatients and inpatients at a university
      hospital. Material and Methods: Based on a detailed process-oriented model we
      calculated the cost and income for port and dialysis catheter implantation, PTA
      at the upper (UL) and lower leg (LL), TACE, SIRT, stent angioplasty (pelvis,
      visceral and supra-aortal vessels) and cerebral coil embolisation for the
      situations mentioned above. Various income models (DRG, GOA) were considered. A
      comprehensive evaluation of the overhead and personnel costs was performed.
      Results: The calculated data (in ?) were as follows (overall, material, personnel
      costs, DRG income, GOA income inpatients, outpatients): port catheter: 375, 266,
      59, 328, 260, 612; dialysis catheter: 456, 349, 59, 272, 343, 807; PTA UL: 595,
      445, 99, 1 240, 425, 1 077; PTA LL: 732, 552, 129, 1 082, 425, 1 184; stent
      pelvis: 1 523, 1 338, 135, 1 323, 815, n/a; stent visceral: 2 124, 1 875, 199, 1
      326, 912, n/a; stent supra-aortal: 1 901, 1 713, 138, 6 705, 1 138, n/a; TACE: 1
      359, 1 120, 188, 2 588, 598, n/a; SIRT: 1 251, 1 054, 147, 2 289, 1 107, n/a;
      intracranial embolisation: 6 684, 6 367, 266, 6 531, n/a, n/a. Conclusion:
      Depending on the income model applied, most procedures caused a deficit,
      especially using GOA calculations. Outpatients covered by the private health
      insurance caused earnings for the procedures applied. Only TACE, SIRT and stent
      angioplasty of supra-aortal vessels caused profits in inpatients using InEK
      calculations.

PMID- 25985225
TI  - [Interactive Knowledge to Action in Health Promotion: The GESTALT Project.
      Initial Results of a Pilot Study on Sustainable Implementation of an Evidence
      Based Programme].
AB  - OBJECTIVES: The present article outlines a pilot study to demonstrate the concept
      of the interactive knowledge to action approach in order to foster sustainable
      implementation of an evidence-based physical activity programme for dementia
      prevention into practice. The approach and procedures will be introduced, and
      initial results of the pilot study "GESTALT", with special regard to the
      interplay of science, politics and prevention practice, will be outlined.
      METHODS: In the GESTALT project (2011-2014) the concept of interactive knowledge
      to action was realised through a cooperative planning approach that
      systematically engaged and involved stakeholders from science, politics and
      practice. Evaluation of the project's sustainability focused on 3 dimensions:
      target group, organisations and context. Target group analysis included
      assessment of changes in physical activity behaviour (n=75). Organisational and
      context evaluations included an analysis of relevant documentation of cooperative
      planning meetings, conduction of the programme, bilateral talks and further
      meetings. RESULTS: In relation to the target group, the majority of participants
      (60%) were committed to an active lifestyle 6 months after completion of the
      GESTALT programme. Regarding organisations and context, 14 partner organisations
      maintained active engagement in cooperative planning processes. After adapting
      the GESTALT programme to the context and needs of the organisations and
      participants, 5 organisations were able to implement it. These same organisations
      also continued to provide exercise classes for ex-participants of the initial
      GESTALT programme. Through developing partnerships, increasing publicity and
      attracting policy makers, resources for the sustainable implementation of the
      GESTALT project were obtained. CONCLUSION: The pilot study GESTALT shows that the
      concept of interactive knowledge to action has substantially contributed to the
      sustainability of a physical activity programme in the field of dementia
      prevention. For this purpose changes in local structures, as well as adaptations
      of the GESTALT programme to the existing structures of prevention practice had to
      be made. The approach of cooperative planning proved to be appropriate for the
      generation of knowledge in terms of practice-based evidence, and it favoured the
      reciprocal adaptation of the GESTALT programme and implementation contexts.

PMID- 25985226
TI  - [Sustainable Implementation of Evidence-Based Programmes in Health Promotion: A
      Theoretical Framework and Concept of Interactive Knowledge to Action].
AB  - OBJECTIVES: This article discusses 2 current issues in the field of public health
      research: (i) transfer of scientific knowledge into practice and (ii) sustainable
      implementation of good practice projects. It also supports integration of
      scientific and practice-based evidence production. Furthermore, it supports
      utilisation of interactive models that transcend deductive approaches to the
      process of knowledge transfer. METHODS: Existing theoretical approaches, pilot
      studies and thoughtful conceptual considerations are incorporated into a
      framework showing the interplay of science, politics and prevention practice,
      which fosters a more sustainable implementation of health promotion programmes.
      The framework depicts 4 key processes of interaction between science and
      prevention practice: interactive knowledge to action, capacity building,
      programme adaptation and adaptation of the implementation context. RESULTS:
      Ensuring sustainability of health promotion programmes requires a concentrated
      process of integrating scientific and practice-based evidence production in the
      context of implementation. Central to the integration process is the approach of
      interactive knowledge to action, which especially benefits from capacity building
      processes that facilitate participation and systematic interaction between
      relevant stakeholders. Intense cooperation also induces a dynamic interaction
      between multiple actors and components such as health promotion programmes,
      target groups, relevant organisations and social, cultural and political
      contexts. The reciprocal adaptation of programmes and key components of the
      implementation context can foster effectiveness and sustainability of programmes.
      CONCLUSION: Sustainable implementation of evidence-based health promotion
      programmes requires alternatives to recent deductive models of knowledge
      transfer. Interactive approaches prove to be promising alternatives.
      Simultaneously, they change the responsibilities of science, policy and public
      health practice. Existing boundaries within disciplines and sectors are overcome
      by arranging transdisciplinary teams as well as by developing common agendas and
      procedures. Such approaches also require adaptations of the structure of research
      projects such as extending the length of funding.

PMID- 25985227
TI  - [Rapid Reviews: Sisyphos' Salvation? - An Inventory].
AB  - Objective and Methods: The aim of this article is to perform an inventory on the
      subject of rapid reviews. Results: Carrying out a systematic review or health
      technology assessment (HTA) is costly and time-consuming. Usually, it takes
      between six months and one year to complete a systematic review, and at least one
      year to complete an HTA. Since questions relating to health care can be urgent,
      decision-makers sometimes need information in a timely manner. Rapid reviews are
      a kind of systematic reviews, which are conducted within shorter timeframes and,
      so, are less expensive. They are characterised by methodological restrictions,
      which can apply at different stages of the review process. Frequently,
      limitations are imposed with respect to literature search and retrieval. However,
      the screening of the title and abstract, full text screening, data extraction and
      quality assessment can also be affected by restrictions. Conclusions: The use of
      rapid review methodology saves time and costs. In situations that require quick
      decisions, rapid reviews are the only option for taking decisions. However,
      methodological restraints may result in greater vulnerability to bias.

PMID- 25985228
TI  - Long-term Therapy With Interleukin 6 Receptor Blockade in Highly Active
      Neuromyelitis Optica Spectrum Disorder.
AB  - IMPORTANCE: Neuromyelitis optica (NMO) is characterized by disabling relapses of
      optic neuritis and myelitis and the presence of aquaporin 4 antibodies (AQP4
      abs). Interleukin 6, which is significantly elevated in serum and cerebrospinal
      fluid of patients with NMO, induces AQP4-ab production by plasmablasts and
      represents a novel therapeutic target. OBJECTIVE: To evaluate the long-term
      safety and efficacy of tocilizumab, a humanized antibody targeting the
      interleukin 6 receptor, in NMO and NMO spectrum disorder. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective observational study with 10 to 51 months of follow-up
      between December 2010 and February 2015, in neurology departments at tertiary
      referral centers. Participants were 8 female patients of white race/ethnicity
      with highly active AQP4-ab-seropositive NMO (n = 6) and NMO spectrum disorder (n
      = 2) whose disease had been resistant to previous medications, including B-cell
      depletion, and who switched to tocilizumab (6-8 mg/kg of body weight per dose).
      MAIN OUTCOMES AND MEASURES: Annualized relapse rate, Expanded Disability Status
      Scale score, spinal cord and brain magnetic resonance imaging, AQP4-ab titers,
      pain levels (numerical rating scale), and adverse effects. RESULTS: Patients were
      followed up for a mean (SD) of 30.9 (15.9) months after switching to tocilizumab.
      Two of eight patients received add-on therapy with monthly corticosteroid pulses
      (temporary) or azathioprine, respectively. During tocilizumab treatment, the
      median annualized relapse rate significantly decreased from 4.0 (interquartile
      range, 3.0-5.0) in the year before tocilizumab therapy to 0.4 (interquartile
      range, 0.0-0.8) (P = .008), and the median Expanded Disability Status Scale score
      significantly decreased from 7.3 (interquartile range, 5.4-8.4) to 5.5
      (interquartile range, 2.6-6.5) (P = .03). Active magnetic resonance imaging
      lesions were seen in 6 of 8 patients at tocilizumab initiation and in 1 of 8
      patients at the last magnetic resonance imaging. Three patients remained relapse
      free during tocilizumab treatment. In 5 patients, a total of 8 relapses occurred,
      4 within the first 21/2 months of therapy. Five attacks were associated with
      delayed tocilizumab administration (>=40 days), and 6 attacks were associated
      with reduced tocilizumab dosage (6 vs 8 mg/kg). The AQP4-ab titers (P = .02) and
      pain levels (P = .02) dropped significantly during tocilizumab treatment. Adverse
      effects included moderate cholesterol elevation in 6 of 8 patients, infections in
      4 of 8 patients, and deep venous thrombosis and neutropenia in one patient each.
      CONCLUSIONS AND RELEVANCE: Prolonged tocilizumab therapy may be safe and
      effective from early treatment phases onward for otherwise therapy-resistant
      highly active NMO and NMO spectrum disorder. Relapse patterns indicate that
      adherence to a regular therapeutic regimen with monthly infusions of tocilizumab
      (8 mg/kg) may increase efficacy.

PMID- 25985229
TI  - Fricative acquisition in English- and Icelandic-speaking preschoolers with
      protracted phonological development.
AB  - Few studies have directly compared fricative development across languages. The
      current study examined voiceless fricative production in Icelandic- versus
      English-speaking preschoolers with protracted phonological development (PPD).
      Expected were: a low fricative match (with age effect), highest match levels for
      /f/ and non-word-initial fricatives, developmentally early mismatch (error)
      patterns including deletion, multiple feature category mismatches or stops, and
      developmentally later patterns affecting only one feature category.
      Crosslinguistic differences in phonetic inventories were predicted to provide
      different options for mismatch patterns, e.g. affricates in English, [+spread
      glottis] segments in Icelandic. For each language, native speakers audio-recorded
      and transcribed single-word speech samples for thirteen 3-year-olds and ten 4
      year-olds. Predictions regarding mismatches were generally confirmed. Accuracy
      data were partially confirmed, /f/ having a lower match than /s/ overall for the
      Icelandic children. Other results reflected language or group differences. The
      data provide confirmation that phonological acquisition reflects crosslinguistic,
      language-specific and child-specific influences. 

PMID- 25985230
TI  - Family Caregiving for Immigrant Seniors Living With Heart Disease and Stroke:
      Chinese Canadian Perspective.
AB  - Heart disease and stroke are two leading causes of death and disability among
      older Canadians. Family support and caregiving are crucial to the positive
      functional recovery and psychological well-being of heart disease and stroke
      survivors. Based on focus groups and individual interviews with Chinese family
      caregivers in the Canadian province of Ontario, we explored the caregiver's
      experience, including the challenges, needs, and service gaps in providing care
      for immigrant seniors with heart disease and stroke. We found that caregiving
      practices and the strategies used to cope with caregiving challenges varied by
      gender, ethnicity, age, and length of migration. We provide recommendations for
      narrowing the gaps in caregiving at the end of the article. 

PMID- 25985231
TI  - Whole-Cell Mediated 11beta-Hydroxylation on the Basic Limonoid Skeleton by
      Cunninghamella echinulata.
AB  - Regio- and stereoselective 11beta-hydroxylation was achieved on the basic
      limonoid skeleton through microbial transformation. Whole cells of Cunninghamella
      echinulata efficiently converted basic limonoids such as epoxyazadiradione,
      azadiradione, and gedunin to their 11beta-hydroxy analogues as the sole
      metabolite. Fermentation conditions affecting the efficiency (96%) of
      biotransformation including substrate concentration, incubation period, pH, and
      temperature were optimized. The position and stereochemistry of hydroxyl
      functionality on the isolated metabolites were established through extensive
      spectroscopic and spectrometric studies (1D, 2D NMR, ESI-MS, and MS/MS). 

PMID- 25985232
TI  - Adaptation of the targeted capture Methyl-Seq platform for the mouse genome
      identifies novel tissue-specific DNA methylation patterns of genes involved in
      neurodevelopment.
AB  - Methyl-Seq was recently developed as a targeted approach to assess DNA
      methylation (DNAm) at a genome-wide level in human. We adapted it for mouse and
      sought to examine DNAm differences across liver and 2 brain regions: cortex and
      hippocampus. A custom hybridization array was designed to isolate 99 Mb of CpG
      islands, shores, shelves, and regulatory elements in the mouse genome. This was
      followed by bisulfite conversion and sequencing on the Illumina HiSeq2000. The
      majority of differentially methylated cytosines (DMCs) were present at greater
      than expected frequency in introns, intergenic regions, near CpG islands, and
      transcriptional enhancers. Liver-specific enhancers were observed to be
      methylated in cortex, while cortex specific enhancers were methylated in the
      liver. Interestingly, commonly shared enhancers were differentially methylated
      between the liver and cortex. Gene ontology and pathway analysis showed that
      genes that were hypomethylated in the cortex and hippocampus were enriched for
      neuronal components and neuronal function. In contrast, genes that were
      hypomethylated in the liver were enriched for cellular components important for
      liver function. Bisulfite-pyrosequencing validation of 75 DMCs from 19 different
      loci showed a correlation of r = 0.87 with Methyl-Seq data. We also identified
      genes involved in neurodevelopment that were not previously reported to be
      differentially methylated across brain regions. This platform constitutes a
      valuable tool for future genome-wide studies involving mouse models of disease.

PMID- 25985233
TI  - Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia.
AB  - Childhood acute lymphoblastic leukemia (ALL) can often be traced to a pre
      leukemic clone carrying a prenatal genetic lesion. Postnatally acquired mutations
      then drive clonal evolution toward overt leukemia. The enzymes RAG1-RAG2 and AID,
      which diversify immunoglobulin-encoding genes, are strictly segregated in
      developing cells during B lymphopoiesis and peripheral mature B cells,
      respectively. Here we identified small pre-BII cells as a natural subset with
      increased genetic vulnerability owing to concurrent activation of these enzymes.
      Consistent with epidemiological findings on childhood ALL etiology,
      susceptibility to genetic lesions during B lymphopoiesis at the transition from
      the large pre-BII cell stage to the small pre-BII cell stage was exacerbated by
      abnormal cytokine signaling and repetitive inflammatory stimuli. We demonstrated
      that AID and RAG1-RAG2 drove leukemic clonal evolution with repeated exposure to
      inflammatory stimuli, paralleling chronic infections in childhood. 

PMID- 25985235
TI  - L-acetylcarnitine for treating fragile X syndrome.
AB  - BACKGROUND: People with fragile X syndrome (FXS) have an intellectual dysfunction
      that can range from very mild to severe. Symptoms can include speech and language
      delays and behavioural difficulties such as aggression or self injurious
      behaviours, emotional lability, and anxiety-related problems (for example
      obsessive-compulsive symptoms and perseverative behaviours). In some cases,
      affected people may have an additional diagnosis of attention deficit
      hyperactivity disorder or an autism spectrum disorder. OBJECTIVES: To review the
      efficacy and safety of L-acetylcarnitine in improving the psychological,
      intellectual, and social performance of people with FXS. SEARCH METHODS: In May
      2015 we searched the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, Embase, PsycINFO, Web of Science, and two other databases. We also
      searched three trials registers, four theses databases, and the reference lists
      of relevant studies and reviews. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) that assessed the efficacy of L-acetylcarnitine, at any dose, in people of
      any age diagnosed with FXS compared with placebo. DATA COLLECTION AND ANALYSIS:
      For each trial, two review authors independently extracted data on the children
      included and interventions compared, and assessed the risk of bias of the studies
      across the following domains: randomisation sequence generation, allocation
      concealment, blinding (of participants, personnel, and outcome assessors),
      incomplete outcome data, selective outcome reporting, and other potential sources
      of bias. MAIN RESULTS: We found only two RCTs that compared oral L
      acetylcarnitine (LAC) with oral placebo in children with FXS. The studies
      included a total of 83 participants, all of them male, who were treated and
      followed for one year. The age of participants at the start of treatment ranged
      from 6 to 13 years, with a mean age of 9 years. Neither study provided
      information on randomisation, allocation concealment procedures, or blinding of
      outcome assessment, and we received no responses from the authors we emailed for
      clarification. We therefore rated studies as being at unclear risk of bias on
      these domains. We judged both studies to be at low risk of bias for blinding of
      participants and personnel, incomplete outcome data, and selective reporting, but
      to be at high risk of other bias, as at least one study was funded by a drug
      company, and in both studies people working for the company were part of the
      research team.We used the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) approach to rate the quality of the available evidence.
      Overall, the quality of the evidence was low due to the imprecision of results
      and high risk of other bias.Regarding the primary outcome of psychological and
      learning capabilities, both studies assessed the effect of interventions on
      children's verbal and non-verbal intellectual functioning using the Wechsler
      Intelligence Scale for Children - Revised. The authors did not provide detailed
      data on those results but said that they found no important differences between
      treatment and placebo.Both studies evaluated the impact of the treatment on
      hyperactive behaviour using the Conners' Abbreviated Parent-Teacher
      Questionnaire. In one study, teachers' assessments of the children found no clear
      evidence of a difference (mean difference (MD) 0.50, 95% confidence interval (CI)
      -5.08 to 6.08, n = 51; low-quality evidence). The other study stated that there
      were no differences between treated and untreated participants, but did not
      provide detailed data for inclusion in the meta-analysis.Parents' assessments
      favoured LAC in one study (MD -0.57, 95% CI -0.94 to -0.19, n = 17; low-quality
      evidence), but not in the other (MD -2.80, 95% CI -7.61 to 2.01, n = 51; low
      quality evidence), though changes were not large enough to be considered
      clinically relevant.Regarding social skills, one study reported no clear evidence
      of a difference in Vineland Adaptive Behavior composite scores (MD 8.20, 95% CI 
      0.02 to 16.42, n = 51; low-quality evidence), yet results in the socialisation
      domain favoured LAC (MD 11.30, 95% CI 2.52 to 20.08, n = 51; low-quality
      evidence).Both studies assessed the safety of the active treatment and recorded
      no side effects. Neither of the included studies assessed the secondary outcome
      of caregiver burden. AUTHORS' CONCLUSIONS: Low-quality evidence from two small
      trials showed that when compared to placebo, LAC may not improve intellectual
      functioning or hyperactive behaviour in children with FXS.

PMID- 25985234
TI  - The chromatin remodeler Brg1 activates enhancer repertoires to establish B cell
      identity and modulate cell growth.
AB  - Early B cell development is orchestrated by the combined activities of the
      transcriptional regulators E2A, EBF1, Foxo1 and Ikaros. However, how the genome
      wide binding patterns of these regulators are modulated during B lineage
      development remains to be determined. Here we found that in lymphoid progenitor
      cells, the chromatin remodeler Brg1 specified the B cell fate. In committed pro-B
      cells, Brg1 regulated contraction of the locus encoding the immunoglobulin heavy
      chain (Igh) and controlled expression of the gene encoding the transcription
      factor c-Myc (Myc) to modulate the expression of genes encoding products that
      regulate ribosome biogenesis. In committed pro-B cells, Brg1 suppressed a pre-B
      lineage-specific pattern of gene expression. Finally, we found that Brg1 acted
      mechanistically to establish B cell fate and modulate cell growth by facilitating
      access of lineage-specific transcription factors to enhancer repertoires. 

PMID- 25985236
TI  - Self-Assembled Poly(3,4-ethylene dioxythiophene):Poly(styrenesulfonate)/Graphene
      Quantum Dot Organogels for Efficient Charge Transport in Photovoltaic Devices.
AB  - We report the self-assembly of poly(3,4-ethylene
      dioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) organogel films
      incorporating graphene quantum dots (GQDs). Because of the electrostatic
      interaction between the GQDs and the PEDOT chains, GQD@PEDOT core-shell
      nanostructures are readily formed. We demonstrate that the GQDs affect the
      reorientation of PEDOT chains and the formation of interconnected structure of
      PEDOT-rich domains, improving the charge transport pathway. The power conversion
      efficiency of the organic photovoltaic device containing the self-assembled
      organogel as the hole extraction layer (HEL) was 26% higher than the device with
      pristine PEDOT-PSS as the HEL.

PMID- 25985237
TI  - Perceptions of Infertility Risks Among Female Pediatric Cancer Survivors
      Following Gonadotoxic Therapy.
AB  - Research has established that childhood cancer treatments can place survivors at
      risk for reproductive health problems, yet little is known about pediatric
      survivors' perceptions of their risk for infertility and worry about future
      family planning. The purpose of this study was to explore factors that affect
      awareness of risk for and worry about infertility among female pediatric cancer
      survivors aged 10 to 21 (N=48) and their parents (N=41) following exposure to
      treatments associated with reproductive late effects. The majority of female
      childhood cancer survivors (71%) and their parents (95%) reported worry about
      infertility following gonadotoxic therapy. Cross-sectional data indicated that
      survivors' awareness of risk for and worry about infertility increase during
      adolescence, whereas parents' awareness of risk and worry generally remain
      constant throughout their daughters' development. Survivor worry about
      infertility was predicted by a variety of factors, yet parent worry about
      infertility was only associated with increased gonadotoxic radiation exposure.
      Overall, these findings reinforce the necessity of developmentally appropriate
      education about reproductive health risks and fertility preservation options
      across the continuum of pediatric oncology care from diagnosis to survivorship. 

PMID- 25985238
TI  - Brain Abscesses Due to Aspergillus nidulans Infection During Induction
      Chemotherapy for Acute Lymphoblastic Leukemia.
AB  - We present the case of a 3-year-old boy who was diagnosed with cerebral abscesses
      due to Aspergillus nidulans infection on day 28 of induction chemotherapy for
      acute lymphoblastic leukemia. He responded well to treatment with voriconazole
      and caspofungin, making a full recovery. There are very few cases of invasive
      aspergillosis reported in children during induction chemotherapy for acute
      leukemia and A. nidulans is rare in the absence of chronic granulomatous disease.

PMID- 25985239
TI  - A Comparison Between Appendiceal and Nonappendiceal Neuroendocrine Tumors in
      Children and Young Adults: A Single-institution Experience.
AB  - BACKGROUND: Pediatric neuroendocrine tumors (NETs) are rare tumors. The purpose
      of this study is to report the clinical characteristics and outcomes of pediatric
      patients treated for NET at a single institution. PROCEDURE: A retrospective
      record review. RESULTS: There were 33 evaluable patients with median age of 17.9
      years (range, 9.9 to 21.9 y) and predominantly females (58%). There were 17
      patients with well-differentiated appendiceal NET, whereas 16 were
      nonappendiceal. Most common nonappendiceal sites were unknown primary (N=6) and
      pancreas (N=4). Majority of tumors were low grade (N=24, 73%) and small (T1,
      N=22, 67%). Nonappendiceal tumors were more likely to be larger or high-grade
      tumors (5/16, 31%), or with metastasis. All appendiceal NET patients underwent
      curative surgery. All patients who experienced treatment failure had
      nonappendiceal NET, despite prior chemotherapy in 8 of 9 patients. The 5-year
      overall survival rates for patients with appendiceal and nonappendiceal NET were
      100% and 66% (95% CI, 45%-95%; P=0.006); and 5-year relapse-free survival rate
      for patients with appendiceal and nonappendiceal NET were 100% and 41% (95% CI,
      22%-75%; P=0.002). CONCLUSIONS: Well-differentiated appendiceal tumors were the
      most common pediatric NET and have an excellent prognosis. Better therapies are
      needed for patients with nonappendiceal NET.

PMID- 25985240
TI  - Hematopoietic Stem Cell Transplantations for Primary Immune Deficiencies: 3
      Decades of Experience From a Tertiary Medical Center.
AB  - Hematopoietic stem cell transplantation (HSCT) remains the leading treatment for
      the majority of severe primary immune deficiency (PID). This study aims to
      analyze changes in outcome over time. We conducted a retrospective analysis of
      HSCT in children with PID in a tertiary medical center over the period of 1983 to
      2012. We identified 93 children with PID with a median follow-up of 3.6 years
      (range, 29 d to 21.2 y) after HSCT. The 2-year survival rates after HSCT for
      children with severe combined immune deficiency, hemophagocytic
      lymphohistiocytosis/lymphoproliferative disease, Wiskott-Aldrich syndrome,
      granulocyte defect, and undefined PID were 65.7%+/-6.8%, 80%+/-10.3%, 83.3%+/
      15.2%, 75%+/-12.5%, and 25%+/-21.7%, respectively. Survival was associated with
      year of HSCT and matching. The hazard ratio (HR) (95% CI) for HSCT done in 1983
      to 1999 compared with 2000 to 2012 and for matched (related and unrelated)
      compared with mismatched donor were 2.14 (0.99 to 4.653) and 3.07 (1.46 to 6.4),
      respectively. Survival was not associated with age, sex of the recipient,
      underlying PID, conditioning regimen, and presence of acute graft-versus-host
      disease. After adjustment to the underlying PID, donor and use of fludarabine
      based conditioning, the HR (95% CI) for HSCT from the year 2000 was 4.69 (range,
      1.4 to 15.45). Advances in HSCT over time have improved the survival of children
      with PID. 

PMID- 25985241
TI  - Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and
      Young Adults With Sickle Cell Disease.
AB  - Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African
      American children with type SS sickle cell disease (SCD-SS). The vit D
      supplemental dose to normalize vit D status is unknown. Five to 20-year-old
      African American children with (n=21) and without (n=23) SCD-SS were randomized
      to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for
      changes in vit D and SCD status. A dose was considered unsafe if serum calcium
      was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At
      baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal
      vit D status (mean+/-SD, 19.2+/-7.2 and 22.3+/-9.3 ng/mL, respectively). After 12
      weeks supplementation, both D3 doses were safe and well tolerated. Neither group
      achieved the a priori efficacy criterion of 25(OH)D>=32 ng/mL in >80% of subjects
      (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and
      healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated
      only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there
      was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high
      sensitivity C-reactive protein, and reduction in the percentage of subjects with
      a high platelet count. 

PMID- 25985242
TI  - Combined Immunosuppression Impairs Immunogenicity to Tetanus and Pertussis
      Vaccination Among Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Pertussis epidemics have recently emerged across the United States,
      prompting broad public health recommendations for adult Tdap vaccination
      (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive
      regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap
      vaccine is not known. METHODS: We performed a prospective controlled trial
      between April 2011 and March 2012. Adults with IBD were consecutively stratified
      based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5
      aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance
      immunomodulator monotherapy; D: combined biologic and immunomodulator therapy;
      and E: healthy age-matched controls. Subjects received Tdap, and serum antibody
      levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin
      (FHA) were drawn just before and approximately 4 weeks after vaccination. The
      primary outcome was the booster response rate to each antigen. Secondary outcomes
      included the differences in pregeometric and postgeometric mean titers. RESULTS:
      A total of 98 subjects enrolled, and 84 completed the study. Tetanus response
      rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group
      D rates were lower than those of group B (P = 0.02). Postvaccination pertussis
      toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%,
      72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and
      postvaccination geometric mean titer differences for FHA were lower in group D
      than those in group A (P = 0.05). CONCLUSIONS: Antibody responses to tetanus and
      pertussis vaccination may be affected by therapeutic drug regimen. Patients with
      IBD should optimally receive Tdap before starting immunomodulators, particularly
      when used in combination with anti-tumor necrosis factor alpha agents.

PMID- 25985243
TI  - Dental Caries and Periodontal Disease in Children and Adolescents with
      Inflammatory Bowel Disease: A Case-Control Study.
AB  - BACKGROUND: Previous reports have demonstrated a higher prevalence of dental
      caries and periodontal disease in adults with inflammatory bowel disease (IBD),
      but similar data in children and adolescents do not exist. The aim of the study
      was to evaluate the status of dental caries, oral hygiene, gingival status and
      periodontal treatment needs of children with IBD. METHODS: In this case-control
      study, 55 children on remission from a single outpatient IBD clinic, aged 4 to 18
      years (12.27 +/- 3.67 yr) and 55 matched systemically healthy controls of a
      dental practice were assessed prospectively. The evaluation included medical
      history, dental questionnaire in both groups, and previous and current medical
      therapy of children with IBD. Additionally, the decayed, missing, and filled
      tooth (dmf-t or DMF-T), simplified gingival, plaque control record and community
      periodontal treatment needs indices were evaluated. RESULTS: Children with IBD
      compared with controls had a statistically significant (P < 0.001) higher dmf-t
      (2.95 versus 0.91) or DMF-T (5.81 versus 2.04) index and a higher gingival
      inflammation (simplified gingival, 40% versus 24%) although the respectively
      dental plaque index showed no significant difference (plaque control record, 42%
      versus 41%). Also, the community periodontal treatment needs was significantly
      higher compared with controls (P < 0.001); most of the patients with IBD needed
      treatment of gingivitis (47% versus 4%), and none of them had healthy
      periodontium (0% versus 69%). CONCLUSIONS: The results of this case-control study
      demonstrate a higher frequency of dental caries, more clinical signs of gingival
      inflammation, and increased periodontal treatment needs in children and
      adolescents with IBD despite similar oral hygiene status.

PMID- 25985245
TI  - Use of Endoscopic Ultrasound to Guide Adalimumab Treatment in Perianal Crohn's
      Disease Results in Faster Fistula Healing.
AB  - BACKGROUND: Perianal disease is a manifestation of Crohn's disease (CD) that has
      poor long-term treatment outcomes. The aim was to determine if rectal endoscopic
      ultrasound (EUS)-guided therapy with adalimumab (ADA) can improve outcomes for
      patients with perianal fistulizing CD. METHODS: This is a randomized prospective
      study comparing serial EUS guidance of fistula treatment versus standard of care
      in fistulizing perianal CD. At enrollment, all patients underwent a rectal EUS
      and an EUA with seton placement and/or I&D. Treatment was maximized with
      immunomodulators, antibiotics, and ADA induction. Surgical interventions were
      determined by the surgeon's discretion in the control group and assisted by every
      12th week EUS in the intervention group. Primary and secondary endpoints where
      complete drainage cessation at week 48 was fistula status per EUS, respectively.
      RESULTS: Twenty patients were enrolled: 11 control and 9 EUS guidance. At 24
      weeks, 7/9 (78%) in EUS group and 3/11 (27%) in control group had drainage
      cessation (P = 0.04). This significant difference was lost at week 48 (P = 0.44).
      Three patients in the EUS and 1 in the control group had additional surgical
      intervention. Those in the EUS group had more rapid escalation of ADA dosing (P =
      0.003). There was no difference in the change in PDAI at week 48 versus baseline
      (P = 0.81). CONCLUSIONS: Rectal EUS-guided ADA therapy for CD perianal fistulas
      showed an initial benefit at 24 weeks, which was lost at week 48. This is likely
      due to small sample size and higher fistula closure in the controls. However, the
      faster rate of fistula resolution is a clinically significant finding.

PMID- 25985244
TI  - Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium.
AB  - BACKGROUND: The role of muscarinic receptors in mucosal homeostasis, response to
      enteric pathogens, and modulation of immune cell function is undefined. METHODS:
      The contribution of type 3 muscarinic receptors (M3R) to mucosal homeostasis
      within the colon and host defense against Citrobacter rodentium was determined in
      uninfected and C. rodentium-infected WT and M3R-deficient (Chrm3) mice. In
      addition, WT and Chrm3 bone marrow-derived macrophages were studied to determine
      the ability of M3R to modulate macrophage phenotype and function. RESULTS: In
      Chrm3 mice, clearance of C. rodentium was delayed despite an amplified TH1/TH17
      response. Delayed clearance of C. rodentium from Chrm3 mice was associated with
      prolonged adherence of bacteria to colonic mucosa, decreased goblet cell number,
      and decreased mucin 2 gene expression. Treatment of bone marrow-derived
      macrophages with bethanechol, a muscarinic-selective agonist, induced a
      classically activated macrophage phenotype, which was dependent on M3R
      expression. Chrm3 bone marrow-derived macrophages retained their ability to
      attain a classically activated macrophage phenotype when treated with the TH1
      cytokine IFN-gamma. CONCLUSIONS: In Chrm3 mice, mucin production is attenuated
      and is associated with prolonged adherence of C. rodentium to colonic mucosa. The
      immune response, as characterized by production of TH1/TH17 cytokines, in C.
      rodentium-infected Chrm3 mice is intact. In addition, M3R activity promotes the
      development of classically activated macrophages. Our data establish a role for
      M3R in host defense against C. rodentium through effects on goblet cell mucus
      production and in the modulation of macrophage phenotype and function.

PMID- 25985246
TI  - Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe
      Crohn's Disease: A Phase 1b/2a Study.
AB  - BACKGROUND: PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal
      like adherent cells with immunomodulatory effects, previously demonstrated safety
      and tolerability in an open-label Crohn's disease (CD) study. The current phase
      1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with
      moderate-to-severe CD. METHODS: Subjects had active inflammation on colonoscopy
      or elevated fecal calprotectin and inadequate response to conventional therapy.
      Concomitant therapy with stable doses of immunomodulators and/or biologics was
      permitted. Subjects received 8 units of PDA-001 (1.5 * 10 cells per unit) in the
      phase 1b open-label study. In the phase 2a double-blind study, subjects were
      randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk
      apart). The primary endpoint was induction of clinical response (>=100 points
      and/or 25% decrease in Crohn's Disease Activity Index) at 4 and 6 weeks. RESULTS:
      Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48
      subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46
      subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo
      (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001
      subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved
      in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One
      treatment-related serious adverse event occurred (systemic hypersensitivity
      reaction at 8 units). In the phase 2a study, serious adverse events occurred in
      9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects. CONCLUSIONS: A
      2-infusion regimen of PDA-001 induced clinical response in subjects with moderate
      to-severe CD. Additional studies are warranted.

PMID- 25985247
TI  - Low Serum Levels of MicroRNA-19 Are Associated with a Stricturing Crohn's Disease
      Phenotype.
AB  - BACKGROUND: Development of fibrosis and subsequent stricture formation in Crohn's
      disease (CD) increases morbidity and rates of surgery and reduces patients'
      quality of life. There are currently no biomarkers of intestinal fibrosis that
      might allow earlier identification and better management of patients at increased
      risk of stricture formation. METHODS: MicroRNA profiling of serum from CD
      patients was used to identify microRNAs associated with stricture formation.
      Differential expression of miR-19a-3p and miR-19b-3p was validated by
      quantitative PCR in independent CD cohort of stricturing and nonstricturing
      patients (n = 46 and n = 62, respectively). Levels of miR-19a-3p and miR-19b-3p
      were also quantified in baseline serum samples, and expression compared between
      CD patients who subsequently developed stricture and those who did not (n = 11
      and n = 44, respectively). RESULTS: Serum levels of miR-19a-3p and miR-19b-3p in
      the array were lower in CD patients with a stricturing phenotype than in control
      CD patients (P = 0.007 and 0.008, respectively). The reduction in miR-19a-3p and
      19b-3p was verified in a second cohort (P = 0.002). The association of miR-19-3p
      with stricturing CD was independent of potential confounding clinical variables,
      including disease duration, disease activity, site, gender, and age. Serum
      analyses in patients with 4 years of follow-up support the hypothesis that
      reduced miR-19a-3p and miR-19b-3p predate stricture development with a trend
      toward significance (P = 0.077 and P = 0.060, respectively). CONCLUSIONS: These
      data identify miR-19-3p as a potential circulating marker of stricturing CD. Our
      data show that microRNAs have utility as noninvasive biomarkers of stricturing
      CD. Further longitudinal studies are required to determine the prognostic value
      of miR-19-3p at diagnosis.

PMID- 25985248
TI  - Short- and Long-Term Outcomes of Acute Severe Ulcerative Colitis in Korea: The
      1999-2005 Cohort.
AB  - BACKGROUND: No previous studies have evaluated the long-term outcomes of acute
      severe ulcerative colitis (ASUC) in non-Caucasian populations. The purposes of
      this study were to evaluate the short- and long-term outcomes of Korean patients
      with ASUC. METHODS: We retrospectively analyzed 99 Korean patients with ASUC who
      satisfied the criteria given by Truelove and Witts between 1999 and 2005. The
      short-term outcome parameter was the colectomy rate during index hospitalization,
      and the long-term outcome parameters were the rates of colectomy and
      rehospitalization after discharge from index hospitalization. RESULTS: During
      index hospitalization, 16 of 99 patients (16.2%) underwent colectomy: 6 of 71
      responders (8.5%) to intravenous steroids on day 3 versus 10 of 28 nonresponders
      (35.7%), as assessed using the Oxford index (P = 0.002). Among 83 patients who
      avoided colectomy during index hospitalization, 13 patients (15.7%) underwent
      colectomy during the median follow-up period of 10.6 years. The cumulative
      probability of colectomy tended to be lower in complete responders on day 7 of
      intravenous steroid therapy (CR7) than in others: 3.7% versus 13.9% at 5 years
      and 7.6% versus 18.2% at 10 years (P = 0.100). The cumulative probability of
      rehospitalization was significantly lower in CR7 than in other patients: 20.5%
      versus 37.5% at 5 years and 31.4% versus 48.2% at 10 years (P = 0.043).
      CONCLUSIONS: Assessing the degree of response to intravenous steroids helps
      predict the short- and long-term outcomes in patients with ASUC. Korean patients
      with ASUC may have better clinical courses than Caucasians, as indicated by the
      lower colectomy rate.

PMID- 25985249
TI  - Therapeutic Armamentarium for Stricturing Crohn's Disease: Medical Versus
      Endoscopic Versus Surgical Approaches.
AB  - One-third of patients with Crohn's disease (CD) present as stricturing phenotype
      characterized by progressive luminal narrowing and obstructive symptoms. The
      diagnosis and management of these patients have been intriguing and challenging.
      Immunomodulators and biologics have been successfully used in treating
      inflammatory and fistulizing CD. There are issues of efficacy and safety of
      biological agents in treating strictures in CD. Rapid mucosal healing from potent
      biological agents may predispose patients to the development of new strictures or
      worsening of existing strictures. On the other hand, strictures constitute one
      fifth of the reasons for surgery in patients with CD. Disease recurrence is
      common at or proximal to the anastomotic site with the majority of these patients
      developing new endoscopic lesions within 1 year of surgery. The progressive
      nature of the disease with repetitive cycle of inflammation and stricture
      formation results in repeated surgery, with a risk of small bowel syndrome. There
      is considerable quest for bowel conserving endoscopic and surgical strategies.
      Endoscopic balloon dilation and stricturoplasty have emerged as valid
      alternatives to resection. Endoscopic balloon dilation has been shown to be
      feasible, safe, and effective for the short primary or anastomotic strictures.
      However, repeated dilations are often needed, and long-term outcomes of
      endoscopic balloon dilation remain to be investigated. The introduction of
      stricturoplasty has added another dimension to bowel saving strategy. Although
      postoperative recurrence rate after stricturoplasty is comparable with surgical
      resection, there are concerns for increased risk of malignancy in preserved
      bowel. Laparoscopic surgery has widely been performed with similar outcomes to
      open approach with fewer complications, quicker recovery, better cosmesis, and
      lower cost. All of these issues should be considered by physicians involved in
      the management of patients with stricturing CD. 

PMID- 25985251
TI  - Fluctuations and synchrony of RNA synthesis in nucleoli.
AB  - Ribosomal RNA (rRNA) sequences are synthesized at exceptionally high rates and,
      together with ribosomal proteins (r-proteins), are utilized as building blocks
      for the assembly of pre-ribosomal particles. Although it is widely acknowledged
      that tight regulation and coordination of rRNA and r-protein production are
      fundamentally important for the maintenance of cellular homeostasis, still little
      is known about the real-time kinetics of the ribosome component synthesis in
      individual cells. In this communication we introduce a label-free MicroRaman
      spectrometric approach for monitoring rRNA synthesis in live cultured cells.
      Remarkably high and rapid fluctuations of rRNA production rates were revealed by
      this technique. Strikingly, the changes in the rRNA output were synchronous for
      ribosomal genes located in separate nucleoli of the same cell. Our findings call
      for the development of new concepts to elucidate the coordination of ribosomal
      components production. In this regard, numerical modeling further demonstrated
      that the production of rRNA and r-proteins can be coordinated, regardless of the
      fluctuations in rRNA synthesis. Overall, our quantitative data reveal a
      spectacular interplay of inherently stochastic rates of RNA synthesis and the
      coordination of gene expression. 

PMID- 25985252
TI  - Effects of contaminated soils from a former iron mine (Ait Amar, Morocco) on
      enchytraeids (Enchytraeus bigeminus) and predatory mites (Hypoaspis aculeifer) in
      standard laboratory tests.
AB  - Mining activity is an important economic activity in several North Atlantic
      Treaty Organization (NATO) and North African countries. Within their territory
      derelict or active mining explorations represent risks to surrounding ecosystems,
      but engineered-based remediation processes are usually too expensive to be an
      option for the reclamation of these areas. A project funded by NATO was
      performed, with the aim of finding a more eco-friendly solution for reclamation
      of these areas. As part of an overall risk assessment, the risk of contaminated
      soils to selected soil organisms was evaluated. The main question addressed was:
      Does the metal-contaminated soils from a former iron mine located at Ait Amar
      (Morocco),which was abandoned in the mid-Sixties, affect the reproduction of
      enchytraeids (Enchytraeus bigeminus) and predatory mites (Hypoaspis aculeifer)?
      Soil samples were taken at 20 plots along four transects covering the mine area
      and at a reference site about 15km away from the mine. The soils were
      characterized pedologically and chemically, which showed a heterogeneous pattern
      of metal contamination (mainly cadmium, copper, and chromium, sometimes at
      concentrations higher than European soil trigger values). The reproduction of
      enchytraeids (Enchytraeus bigeminus) and predatory mites (Hypoaspis aculeifer)
      was studied using standard laboratory tests according to OECD guidelines 220
      (2004) and 226 (2008). The number of juveniles of E. bigeminus was reduced at
      several plots with high concentrations of Cd or Cu (the latter in combination
      with low pH values). There was nearly no effect of the metal contaminated soils
      on the reproduction of H. aculeifer. The overall lack of toxicity at the majority
      of the studied plots is probably caused by the low availability of the metals in
      these soils unless soil pH was very low. Different exposure pathways are likely
      responsible for the different reaction of mites and enchytraeids (hard-bodied
      versus soft-bodied organisms). The results of this study can be used not only for
      assessing the risk of contaminated soils but also could play a role for the
      identification of soil remediation programs. 

PMID- 25985250
TI  - Biomarkers of Inflammatory Bowel Disease: From Classical Laboratory Tools to
      Personalized Medicine.
AB  - Diagnostics of inflammatory bowel diseases (IBDs) currently relies on a
      combination of biological and morphological tests. The current method of
      diagnostic remains a critical challenge for physicians in part due to their
      invasiveness and also for their limitations in term of diagnosis, prognosis,
      disease activity and severity assessment, and therapeutic outcomes. Laboratory
      biomarkers can be used in the diagnosis and management of IBD, but none of them
      has been proven to be ideal. Increasing efforts are being made to discover new
      biomarkers that can discriminate between the types of IBD, predict future
      responses to treatment, and aid in differential diagnosis, treatment planning,
      and prognosis prediction. This review addresses the potential for current
      biomarkers and the emergence of the concept of biomarker signatures in IBD
      diagnostic and personalized medicine. 

PMID- 25985253
TI  - The role of self-esteem instability in the development of postnatal depression: A
      prospective study testing a diathesis-stress account.
AB  - BACKGROUND AND OBJECTIVES: Understanding vulnerability factors involved in the
      development of postnatal depression has important implications for theory and
      practice. In this prospective study, we investigated whether self-esteem
      instability during pregnancy would better predict postnatal depressive
      symptomatology than level of self-esteem. In addition, going beyond former
      studies, we tested the possible origin of this instability, examining whether day
      to-day fluctuations in self-esteem could be explained by fluctuations in mood
      state, and whether this day-to-day self-esteem reactivity would predict postnatal
      depressive symptoms. METHODS: 114 healthy never-depressed women were tested
      during the late second or third trimester of their gestation (Time 1) and at 12
      weeks after delivery (Time 2). Day-to-day levels of self-esteem and depressed
      mood state were assessed at Time 1. At Time 2, postnatal depressive symptoms were
      assessed. RESULTS: The results show that, after controlling for initial
      depressive symptomatology, age and socio-economic status, postnatal depressive
      symptomatology at 12 weeks after childbirth could be predicted by self-esteem
      instability and not level of self-esteem. In addition, multi-level analyses
      demonstrated that these changes in day-to-day levels of self-esteem are
      associated with changes in day-to-day levels of depressed mood state and that
      those subjects with greater prenatal self-esteem reactivity upon depressed mood
      report higher levels of depressive symptoms post-partum. LIMITATIONS: We used
      paper and pencil day-to-day measures of state self-esteem, which can be subject
      to bias. CONCLUSION: These results provide evidence for a diathesis-stress
      account of postnatal depression, highlighting the importance of a multi
      dimensional view of self-esteem and the predictive role of self-esteem
      instability.

PMID- 25985254
TI  - Defining Transfusion Triggers and Utilization of Fresh Frozen Plasma and
      Platelets Among Patients Undergoing Hepatopancreaticobiliary and Colorectal
      Surgery.
AB  - BACKGROUND: We sought to define the overall utilization of fresh frozen plasma
      (FFP) and platelets and the impact on perioperative outcomes among patients
      undergoing hepatopancreaticobiliary and colorectal resections, as well as analyze
      the utility of laboratory triggers in guiding transfusion practice. METHODS: We
      identified 3027 patients undergoing pancreatic, hepatic, and colorectal
      resections between 2010 and 2013 at Johns Hopkins Hospital. Data on international
      normalized ratio (INR) and platelet counts that triggered the perioperative
      utilization of these non-RBC (red blood cell) products were obtained and
      analyzed. RESULTS: Overall FFP and platelet transfusion rates were 8.9% and 3.8%,
      respectively. Mean INR and platelet triggers for FFP and platelet transfusions
      were 1.9 +/- 1.3 and 60000 +/- 44000, respectively. INR triggers varied depending
      on resection type, patient race, and comorbidity status (all P <0.05). Nearly one
      half of patients (48.0%) received FFP in the postoperative period with an INR
      trigger less than 1.7. FFP transfusions were independently associated with an
      increased length of stay [odds ratio (OR) = 3.66], perioperative morbidity (OR =
      3.96) and in-hospital mortality (OR = 91.85) (all P < 0.001). Similarly, patients
      receiving platelets were at increased risk for worse overall perioperative
      outcomes (all OR >1, P <0.001). CONCLUSIONS: The utilization and indication of
      non-RBC components vary significantly across surgical specialties. Nearly one
      half of patients transfused with FFP during the postoperative period had an INR
      of less than 1.7, indicating possible overutilization of these products.
      Furthermore, the use of FFP and platelets are associated with poorer
      perioperative outcomes. Further studies are needed to study the impact and
      management of a more restrictive use of FFP and platelets on surgical patients.

PMID- 25985255
TI  - Conformational Changes in Pigment-Protein Complexes at Low Temperatures-Spectral
      Memory and a Possibility of Cooperative Effects.
AB  - We employed nonphotochemical hole burning (NPHB) and fluorescence line narrowing
      (FLN) spectroscopies to explore protein energy landscapes and energy transfer
      processes in dimeric Cytochrome b6f, containing one chlorophyll molecule per
      protein monomer. The parameters of the energy landscape barrier distributions
      quantitatively agree with those reported for other pigment-protein complexes
      involved in photosynthesis. Qualitatively, the distributions of barriers between
      protein substates involved in the light-induced conformational changes (i.e., 
      NPHB) are close to glass-like ~1/?V (V is the barrier height) and not to
      Gaussian. There is a high degree of correlation between the heights of the
      barriers in the ground and excited states in individual pigment-protein systems,
      as well as nearly perfect spectral memory. Both NPHB and hole recovery are due to
      phonon-assisted tunneling associated with the increase of the energy of a
      scattered phonon. As the latter is unlikely for simultaneously both the hole
      burning and the hole recovery, proteins must exhibit a NPHB mechanism involving
      diffusion of the free volume toward the pigment. Entities involved in the light
      induced conformational changes are characterized by md(2) value of about 1.0 *
      10(-46) kg.m(2). Thus, these entities are protons or, alternatively, small groups
      of atoms experiencing sub-A shifts. However, explaining all spectral hole burning
      and recovery data simultaneously, employing just one barrier distribution,
      requires a drastic decrease in the attempt frequency to about 100 MHz. This
      decrease may occur due to cooperative effects. Evidence is presented for
      excitation energy transfer between the chlorophyll molecules of the adjacent
      monomers. The magnitude of the dipole-dipole coupling deduced from the Delta-FLN
      spectra is in good agreement with the structural data, indicating that the
      explored protein was intact. 

PMID- 25985256
TI  - Cascade morphology transition in bcc metals.
AB  - Energetic atom collisions in solids induce shockwaves with complex morphologies.
      In this paper, we establish the existence of a morphological transition in such
      cascades. The order parameter of the morphology is defined as the exponent, b, in
      the defect production curve as a function of cascade energy (N(F) ~ E(MD)(b)).
      Response of different bcc metals can be compared in a consistent energy domain
      when the energy is normalized by the transition energy, MU, between the high- and
      the low-energy regime. Using Cr, Fe, Mo and W data, an empirical formula of MU as
      a function of displacement threshold energy, E(d), is presented for bcc metals.

PMID- 25985258
TI  - Electrocatalytic Water Oxidation by a Water-Soluble Nickel Porphyrin Complex at
      Neutral pH with Low Overpotential.
AB  - The water-soluble cationic nickel(II) complex of meso-tetrakis(4-N
      methylpyridyl)porphyrin (1) can electrocatalyze water oxidation to O2 in neutral
      aqueous solution (pH 7.0) with the onset of the catalytic wave appearing at ~1.0
      V (vs NHE). The homogeneous catalysis with 1 was verified. Catalyst 1 exhibited
      water oxidation activity in a pH range 2.0-8.0 and had a strict linear dependence
      of catalytic current on its concentration. After 10 h of constant potential
      electrolysis at 1.32 V (vs NHE), a negligible difference of the solution was
      observed by UV-vis. In addition, inspection of the working electrode by
      electrochemistry, scanning electron microscope (SEM), and energy dispersive X-ray
      spectroscopy (EDX) showed no sign of deposition of NiOx films. These results
      strongly argued that 1 is a real molecular electrocatalyst for water oxidation.
      The turnover frequency (TOF) for this process was 0.67 s(-1) at 20  degrees C. On
      the basis of results from the kinetic isotope effect (KIE) and inhibition
      experiments, electrochemical studies in various buffer solutions with different
      anions and pHs, and DFT calculations, a catalytic cycle of 1 for water oxidation
      via a formally Ni(IV) species was proposed. 

PMID- 25985257
TI  - Protein stabilization utilizing a redefined codon.
AB  - Recent advances have fundamentally changed the ways in which synthetic amino
      acids are incorporated into proteins, enabling their efficient and multiple-site
      incorporation, in addition to the 20 canonical amino acids. This development
      provides opportunities for fresh approaches toward addressing fundamental
      problems in bioengineering. In the present study, we showed that the structural
      stability of proteins can be enhanced by integrating bulky halogenated amino
      acids at multiple selected sites. Glutathione S-transferase was thus stabilized
      significantly (by 5.2 and 5.6 kcal/mol) with 3-chloro- and 3-bromo-l-tyrosines,
      respectively, incorporated at seven selected sites. X-ray crystallographic
      analyses revealed that the bulky halogen moieties filled internal spaces within
      the molecules, and formed non-canonical stabilizing interactions with the
      neighboring residues. This new mechanism for protein stabilization is quite
      simple and applicable to a wide range of proteins, as demonstrated by the rapid
      stabilization of the industrially relevant azoreductase.

PMID- 25985259
TI  - Why some colors appear more memorable than others: A model combining categories
      and particulars in color working memory.
AB  - Categorization with basic color terms is an intuitive and universal aspect of
      color perception. Yet research on visual working memory capacity has largely
      assumed that only continuous estimates within color space are relevant to memory.
      As a result, the influence of color categories on working memory remains unknown.
      We propose a dual content model of color representation in which color matches to
      objects that are either present (perception) or absent (memory) integrate
      category representations along with estimates of specific values on a continuous
      scale ("particulars"). We develop and test the model through 4 experiments. In a
      first experiment pair, participants reproduce a color target, both with and
      without a delay, using a recently influential estimation paradigm. In a second
      experiment pair, we use standard methods in color perception to identify boundary
      and focal colors in the stimulus set. The main results are that responses drawn
      from working memory are significantly biased away from category boundaries and
      toward category centers. Importantly, the same pattern of results is present
      without a memory delay. The proposed dual content model parsimoniously explains
      these results, and it should replace prevailing single content models in studies
      of visual working memory. More broadly, the model and the results demonstrate how
      the main consequence of visual working memory maintenance is the amplification of
      category related biases and stimulus-specific variability that originate in
      perception.

PMID- 25985260
TI  - Is dispositional optimism or dispositional pessimism predictive of ideal
      cardiovascular health? The Young Finns Study.
AB  - OBJECTIVE: We examined the independent association between dispositional optimism
      compared to dispositional pessimism and ideal cardiovascular health (defined by
      the American Heart Association). DESIGN: A prospective design with a study sample
      of 1113 participants aged 24-39 years from the longitudinal Young Finns Study.
      MAIN OUTCOME MEASURES: Ideal cardiovascular health (comprised of seven ideal
      cardiovascular health metrics) was measured in 2001. The ideal cardiovascular
      health metrics were reassessed in 2007. RESULTS: Low pessimism rather than high
      optimism was a better predictor of ideal cardiovascular health in 2007. When
      examining the association between optimism and pessimism and the seven ideal
      cardiovascular health metrics in 2007 (BMI, diet, physical activity, smoking
      status, blood pressure, total cholesterol and plasma glucose), low pessimism
      predicted non-smoking status, ideal physical activity and eating a healthy diet,
      while high optimism was associated with eating a healthy diet. CONCLUSION: Our
      findings suggest that low pessimism rather than high optimism is associated with
      ideal cardiovascular health, especially with health behaviours such as not
      smoking, being physically active and eating a healthy diet. Socio-economic status
      was the potential mediating or confounding factor. Future studies should examine
      the differential meaning of the optimism/pessimism concepts to further clarify
      their relation to health outcomes.

PMID- 25985261
TI  - Outdoor activities and depressive symptoms in displaced older adults following
      natural disaster: community cohesion as mediator and moderator.
AB  - OBJECTIVES: This investigation examined whether community cohesion mediates or
      moderates the relationship between outdoor activities and depressive symptoms in
      older adults displaced by Typhoon Morakot in Taiwan. METHOD: This cross-sectional
      study included 292 adults aged 65 years or older who were relocated to permanent
      houses after Typhoon Morakot damaged their homes on 8th August 2009. Multiple
      regression analysis was applied to test the role of community cohesion on the
      association between outdoor activities and depressive symptoms. RESULTS: The
      sample of displaced older adults displayed higher prevalence of depressive
      symptoms than the average for community dwelling older people in Taiwan.
      Community cohesion fully mediated the relationship between outdoor activities and
      depressive symptoms. Community cohesion also moderated the relationship between
      outdoor activities and depressive symptoms. CONCLUSION: Community cohesion
      occupies a key role on the link between outdoor activities and depressive
      symptoms. Participation in outdoor activities was associated positively with
      community cohesion, while high community cohesion was related negatively to
      depressive symptoms. Additionally, the benefit of outdoor activities to fewer
      depressive symptoms only manifested in older adults with high community cohesion.
      Programs and services should be designed to enhance community cohesion in order
      to maximize the benefit of outdoor activities to the mental health of displaced
      older adults after natural disasters.

PMID- 25985262
TI  - In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency.

PMID- 25985264
TI  - Novel, Facile, Single-Step Technique of Polymer/TiO2 Nanofiber Composites
      Membrane for Photodegradation of Methylene Blue.
AB  - Novel photocatalyst membrane materials were successfully fabricated by an air jet
      spinning (AJS) technique from polyvinyl acetate (PVAc) solutions containing
      nanoparticles (NPs) of titanium dioxide (TiO2). Our innovative strategy for the
      production of composite nanofibers is based on stretching a solution of polymer
      with a high-speed compressed air jet. This enabled us to rapidly cover different
      substrates with TiO2/PVAc interconnected nanofibers. Surprisingly, the diameters
      of the as-spun fibers were found to decrease with increasing amount of NPs. Our
      results showed that AJS PVAc-based fibrous membranes with average fiber diameters
      of 505-901 nm have an apparent porosity of about 79-93% and a mean pore size of
      1.58-5.12 MUm. Embedding NPs onto the as-spun fibers resulted in increasing the
      tensile strength of the obtained composite fiber mats. The photodegradation
      property of TiO2 membrane mats proved a high efficiency in the decomposition of
      methylene blue dye. The novel fiber spinning technique discussed in this paper
      can provide the capacity to lace together a variety of types of polymers, fibers
      and particles to produce interconnected fibers layer. Our approach, therefore,
      opens the door for the innovation in nanocomposite mat that has great potential
      as efficient and economic water filter media and as reusable photocatalyst. 

PMID- 25985266
TI  - First-principles-based effective Hamiltonian simulations of bulks and films made
      of lead-free Ba(Zr,Ti)O3 relaxor ferroelectrics.
AB  - A review of the recent development and application of a first-principles-derived
      effective Hamiltonian technique to the study of lead-free Ba(Zr,Ti)O3 (BZT)
      relaxor ferroelectrics is provided. In addition to the computation and analysis
      of macroscopic properties (such as different types of dielectric responses and
      electric polarization) and their connections to previous published works,
      particular emphasis is given to microscopic insights arising from this atomistic
      technique. These include (i) the numerically-found determination of the physical
      origin of the relaxor behavior in BZT; and (ii) the prediction of polar
      nanoregions and the evolution of their morphology as a response to temperature,
      electric fields and epitaxial misfit strain. Other striking phenomena that were
      predicted in BZT compounds, such as Fano resonance and field-driven percolation,
      are also documented and discussed. Finally, a brief perspective of possible
      remaining computational studies to be conducted in relaxor ferroelectrics, in
      order to further understand them, is attempted. 

PMID- 25985263
TI  - Comprehensive transcriptome analysis using synthetic long-read sequencing reveals
      molecular co-association of distant splicing events.
AB  - Alternative splicing shapes mammalian transcriptomes, with many RNA molecules
      undergoing multiple distant alternative splicing events. Comprehensive
      transcriptome analysis, including analysis of exon co-association in the same
      molecule, requires deep, long-read sequencing. Here we introduce an RNA
      sequencing method, synthetic long-read RNA sequencing (SLR-RNA-seq), in which
      small pools (<=1,000 molecules/pool, <=1 molecule/gene for most genes) of full
      length cDNAs are amplified, fragmented and short-read-sequenced. We demonstrate
      that these RNA sequences reconstructed from the short reads from each of the
      pools are mostly close to full length and contain few insertion and deletion
      errors. We report many previously undescribed isoforms (human brain: ~13,800
      affected genes, 14.5% of molecules; mouse brain ~8,600 genes, 18% of molecules)
      and up to 165 human distant molecularly associated exon pairs (dMAPs) and distant
      molecularly and mutually exclusive pairs (dMEPs). Of 16 associated pairs detected
      in the mouse brain, 9 are conserved in human. Our results indicate conserved
      mechanisms that can produce distant but phased features on transcript and
      proteome isoforms. 

PMID- 25985265
TI  - Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients
      with bipolar depression.
AB  - OBJECTIVE: Bipolar disorder imposes a high economic burden on patients and
      society. Lurasidone and quetiapine extended-release (XR) are atypical
      antipsychotic agents indicated for monotherapy treatment of bipolar depression.
      Lurasidone is also indicated as adjunctive therapy with lithium or valproate for
      depressive episodes associated with bipolar disorder. The objective of this
      analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR
      in patients with bipolar depression. METHODS: A cost-effectiveness model was
      developed to compare lurasidone to quetiapine XR. The model was based on a US
      third-party payer perspective over a 3-month time horizon. The effectiveness
      measure in the model was the percentage of patients achieving remission
      (Montgomery-Asberg Depression Rating Scale [MADRS] total score <=12 by weeks 6
      8). The comparison of remission rates was made through an adjusted indirect
      treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo
      as the common comparator. Resource utilization for remission vs no remission was
      estimated from published expert panel data, and resource costs were obtained from
      a retrospective database study of bipolar I depression patients. Drug costs were
      estimated using the mean dose from clinical trials and wholesale acquisition
      costs. RESULTS: Over the 3-month model time period, lurasidone and quetiapine XR
      patients, respectively, had similar mean numbers of emergency department visits
      (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More
      lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with
      slightly higher total costs ($4982 vs $4676), resulting in an incremental cost
      effectiveness ratio of $3474 per remission. The probabilistic sensitivity
      analysis showed lurasidone had an 86% probability of being cost-effective
      compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per
      remission. CONCLUSIONS: Lurasidone may be a cost-effective option when compared
      to quetiapine XR for the treatment of adults with bipolar depression.

PMID- 25985267
TI  - PERCEIVING TIME-TO-CONTACT UNDER LOCALLY IMPOVERISHED OPTICAL FLOW.
AB  - As an object approaches an observer, the visual angle subtended by any two
      texture elements on the object surface expands, as does the solid angle
      corresponding to the object's contour. The inverse of the relative rate of each
      of these types of expansion specifies the time-to-contact (TTC) between the
      object and the observer. The former is referred to as local tau1 (LT1), and the
      latter as local tau2 (LT2). For LT1 and LT2 to be available, the shape of the
      object must remain constant during its approach. The present study examined human
      observers' perceptual capacity to estimate TTC of an approaching object under
      severely perturbed or impoverished optic flow. In Experiment 1, non-spherical,
      textureless objects approached the observer while rotating about either one or
      two axes. In Experiment 2, textured objects were depicted by random dots that
      varied in density. When the object rotated, the surface dots were displaced or
      even disappeared. These manipulations severely compromised the optical patterns
      specifying LT1 and LT2. However, human observers were able to estimate TTC,
      although less reliably, under these severely compromised conditions.

PMID- 25985268
TI  - Discrimination between streptavidin and avidin with fluorescent affinity-based
      probes.
AB  - Two biotinylated coumarin-based fluorescent probes SPS3 and RC3 were designed for
      differentiating between structurally similar proteins streptavidin (SA) and
      avidin (AV). A substituted phenyl group is introduced onto SPS3, which may quench
      the fluorescence through twist intramolecular charge transfer (TICT). The
      fluorescence of SPS3 is turned on, by restraining the TICT process, when the
      fluorophore is buried at the surface of SA. RC3 is constructed by incorporating a
      biotin molecule to a coumarin fluorophore through a 4-atom spacer. The
      fluorescence intensity of RC3 is enhanced significantly when its fluorophore
      enters into the less polar binding pocket of AV. SPS3 and RC3 could be applied in
      distinguishing between SA and AV as well as in fluorescence imaging of biotin
      receptor over-expressed Hela cells. 

PMID- 25985269
TI  - Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth
      and potency.
AB  - While current HIV-1 therapies have greatly improved the quality and duration of
      life for infected individuals, a vaccine to prevent transmission of the virus is
      lacking. Broadly neutralizing monoclonal antibodies (bnmAbs) with the capacity to
      neutralize multiple HIV-1 variants have been isolated from HIV-1-infected
      individuals, and there has been a great effort to investigate how these bnmAbs
      arise, due their potential for HIV-1 vaccination. In this issue of the JCI,
      Willis and colleagues apply a computational approach to design variants of the
      bnmAb PG9 in an attempt to enhance potency and neutralization breadth. One of
      these variants was able to target multiple PG9-resistant strains, as the result
      of stabilization of the long heavy chain complementarity determining region 3
      (HCDR3). The results of this study provide important insight and a unique
      approach to optimizing HIV-1 bnmABs. 

PMID- 25985271
TI  - Fertility and fragrance: another cause of Kallmann syndrome.
AB  - Kallmann syndrome is an inherited deficiency of gonadotropin-releasing hormone
      (GnRH) that is characterized by hypogonadism with delayed or absent puberty and
      dysfunctional olfaction. While Kallmann syndrome-associated mutations have been
      identified in some sets of patients, for many of these individuals, the
      underlying cause remains unknown. In this issue of the JCI, Cariboni and
      colleagues identify mutations in semaphorin 3E (SEMA3E) in two brothers with
      Kallmann syndrome. In animal models, loss of SEMA3E signaling recapitulated
      phenotypes of the probands and resulted in enhanced GnRH neuron death during
      development. The results of this study offer important insight into the
      development of Kallmann syndrome and provide tools for elucidating mutations that
      underlie complex hormonal phenotypes. 

PMID- 25985272
TI  - Kidney growth and hypertrophy: the role of mTOR and vesicle trafficking.
AB  - The kidney, like other organs, grows in constant proportion to the rest of the
      body. When one kidney is removed, the remaining one hypertrophies. In a
      comprehensive series of studies, Chen et al. show that growth during maturation
      is mediated by the mTORC1 signaling pathway, which is induced by EGF-like
      peptides, and requires PI3K, PDK, AKT, mTORC2, and activation of mTORC1 through
      the combined effects of TSC and RHEB as part of a multiprotein complex localized
      on lysosomes. However, compensatory growth is mediated by amino acids, which act
      on mTORC1 independently of the previous pathway, and requires a class III PI3K
      (VPS34) that is known to be involved in vesicle trafficking to the lysosomes. 

PMID- 25985273
TI  - Phosphatidylinositol 3-kinase signaling determines kidney size.
AB  - Kidney size adaptively increases as mammals grow and in response to the loss of 1
      kidney. It is not clear how kidneys size themselves or if the processes that
      adapt kidney mass to lean body mass also mediate renal hypertrophy following
      unilateral nephrectomy (UNX). Here, we demonstrated that mice harboring a
      proximal tubule-specific deletion of Pten (Pten(ptKO)) have greatly enlarged
      kidneys as the result of persistent activation of the class I PI3K/mTORC2/AKT
      pathway and an increase of the antiproliferative signals p21(Cip1/WAF) and
      p27(Kip1). Administration of rapamycin to Pten(ptKO) mice diminished hypertrophy.
      Proximal tubule-specific deletion of Egfr in Pten(ptKO) mice also attenuated
      class I PI3K/mTORC2/AKT signaling and reduced the size of enlarged kidneys. In
      Pten(ptKO) mice, UNX further increased mTORC1 activation and hypertrophy in the
      remaining kidney; however, mTORC2-dependent AKT phosphorylation did not increase
      further in the remaining kidney of Pten(ptKO) mice, nor was it induced in the
      remaining kidney of WT mice. After UNX, renal blood flow and amino acid delivery
      to the remaining kidney rose abruptly, followed by increased amino acid content
      and activation of a class III PI3K/mTORC1/S6K1 pathway. Thus, our findings
      demonstrate context-dependent roles for EGFR-modulated class I PI3K/mTORC2/AKT
      signaling in the normal adaptation of kidney size and PTEN-independent, nutrient
      dependent class III PI3K/mTORC1/S6K1 signaling in the compensatory enlargement of
      the remaining kidney following UNX.

PMID- 25985270
TI  - T cells in the control of organ-specific autoimmunity.
AB  - Immune tolerance is critical to the avoidance of unwarranted immune responses
      against self antigens. Multiple, non-redundant checkpoints are in place to
      prevent such potentially deleterious autoimmune responses while preserving
      immunity integral to the fight against foreign pathogens. Nevertheless, a large
      and growing segment of the population is developing autoimmune diseases.
      Deciphering cellular and molecular pathways of immune tolerance is an important
      goal, with the expectation that understanding these pathways will lead to new
      clinical advances in the treatment of these devastating diseases. The vast
      majority of autoimmune diseases develop as a consequence of complex mechanisms
      that depend on genetic, epigenetic, molecular, cellular, and environmental
      elements and result in alterations in many different checkpoints of tolerance and
      ultimately in the breakdown of immune tolerance. The manifestations of this
      breakdown are harmful inflammatory responses in peripheral tissues driven by
      innate immunity and self antigen-specific pathogenic T and B cells. T cells play
      a central role in the regulation and initiation of these responses. In this
      Review we summarize our current understanding of the mechanisms involved in these
      fundamental checkpoints, the pathways that are defective in autoimmune diseases,
      and the therapeutic strategies being developed with the goal of restoring immune
      tolerance. 

PMID- 25985276
TI  - Use of context in emotion perception: The role of top-down control, cue type, and
      perceiver's age.
AB  - Although context is crucial to emotion perception, there are various factors that
      can modulate contextual influence. The current research investigated how cue
      type, top-down control, and the perceiver's age influence attention to context in
      facial emotion perception. In 2 experiments, younger and older adults identified
      facial expressions contextualized by other faces, isolated objects, and scenes.
      In the first experiment, participants were instructed to ignore face, object, and
      scene contexts. Face context was found to influence perception the least, whereas
      scene context produced the most contextual effect. Older adults were more
      influenced by context than younger adults, but both age groups were similarly
      influenced by different types of contextual cues, even when they were instructed
      to ignore the context. In the second experiment, when explicitly instructed that
      the context had no meaningful relationship to the target, younger and older
      adults both were less influenced by context than when they were instructed that
      the context was relevant to the target. Results from both studies indicate that
      contextual influence on emotion perception is not constant, but can vary based on
      the type of contextual cue, cue relevance, and the perceiver's age.

PMID- 25985274
TI  - Redesigned HIV antibodies exhibit enhanced neutralizing potency and breadth.
AB  - Several HIV envelope-targeting (Env-targeting) antibodies with broad and potent
      neutralizing activity have been identified and shown to have unusual features. Of
      these, the PG9 antibody has a long heavy chain complementarity determining region
      3 (HCDR3) and possesses unique structural elements that interact with protein and
      glycan features of the HIV Env glycoprotein. Here, we used the Rosetta software
      suite to design variants of the PG9 antibody HCDR3 loop with the goal of
      identifying variants with increased potency and breadth of neutralization for
      diverse HIV strains. One variant, designated PG9_N100(F)Y, possessed increased
      potency and was able to neutralize a diverse set of PG9-resistant HIV strains,
      including those lacking the Env N160 glycan, which is critical for PG9 binding.
      An atomic resolution structure of the PG9_N100(F)Y fragment antigen binding (Fab)
      confirmed that the mutated residue retains the paratope surface when compared
      with WT PG9. Differential scanning calorimetry experiments revealed that the
      mutation caused a modest increase in thermodynamic stability of the Fab, a
      feature predicted by the computational model. Our findings suggest that
      thermodynamic stabilization of the long HCDR3 in its active conformation is
      responsible for the increased potency of PG9_N100(F)Y, and strategies aimed at
      stabilizing this region in other HIV antibodies could become an important
      approach to in silico optimization of antibodies.

PMID- 25985277
TI  - Understanding the Value of Continuity in the 21st Century.

PMID- 25985275
TI  - Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron
      deficiency in Kallmann syndrome.
AB  - Individuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH)
      have impaired sexual reproduction. Previous genetic linkage studies and
      sequencing of plausible gene candidates have identified mutations associated with
      inherited GnRH deficiency, but the small number of affected families and limited
      success in validating candidates have impeded genetic diagnoses for most
      patients. Using a combination of exome sequencing and computational modeling, we
      have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers
      with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant
      wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a
      plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival
      signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation
      did not protect GnRH neurons from death. In murine models, lack of either SEMA3E
      or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing
      innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron
      deficiency in male mice was accompanied by impaired testes growth, a
      characteristic feature of KS. Together, these results identify SEMA3E as an
      essential gene for GnRH neuron development, uncover a neurotrophic function for
      SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a
      mechanism that prevents GnRH neuron deficiency. 

PMID- 25985278
TI  - Gene-inspired mycosynthesis of skeletally new indole alkaloids.
AB  - Dalesindole, an antibacterial and anti-inflammatory indole alkaloid with an
      undescribed carbon skeleton, was stereoselectively constructed by Daldinia
      eschscholzii through class II aldolase catalyzed Michael addition of fungal
      chromone with 3,3'-diindolylmethane (DIM) formed in situ from indole-3-carbinol
      (I3C) under catalyses of monooxygenase and 8-amino-7-oxononanoate synthase
      (AONS). Dalesindole isomerizes via a retro-Michael reaction to give stereoisomers
      with bioactivities. The work provides an access to new bioactive hybrids of
      fungal oligoketide with microbially decorated exogenous chemistry. 

PMID- 25985279
TI  - A focus on pleasure? Desire and disgust in group work with young men.
AB  - There are a number of persuasive arguments as to why sexual pleasure should be
      included in sexual health work with young people, including the suggestion that
      this would provide young people with accounts of gender and sexuality that are
      more critical and holistic than those presented in the popular media, pornography
      and current sex education curricula. This paper considers the possibilities for
      engaging young men in critical group work about sexual pleasure in research and
      education contexts, drawing on a mixed-methods study of young people's
      understandings and experiences of 'good sex'. The paper provides a reflexive
      account of one focus group conducted with a group of heterosexual young men and
      two youth educators. It explores some of the challenges to building relationships
      with young men and creating 'safe spaces' in which to engage in critical
      sexuality education in socially unequal contexts. In this case study, adult-led
      discussion elicits rebellious, 'hyper-masculine' performances that close down
      opportunities for critical or reflective discussion. Although there are some
      opportunities for critical work that move beyond limited public health or school
      based sex education agendas, there is also space for collusion and the
      reinforcement of oppressive social norms. The paper concludes by imagining
      possibilities for future research and practice. 

PMID- 25985280
TI  - Emergent complex network geometry.
AB  - Networks are mathematical structures that are universally used to describe a
      large variety of complex systems such as the brain or the Internet.
      Characterizing the geometrical properties of these networks has become
      increasingly relevant for routing problems, inference and data mining. In real
      growing networks, topological, structural and geometrical properties emerge
      spontaneously from their dynamical rules. Nevertheless we still miss a model in
      which networks develop an emergent complex geometry. Here we show that a single
      two parameter network model, the growing geometrical network, can generate
      complex network geometries with non-trivial distribution of curvatures, combining
      exponential growth and small-world properties with finite spectral
      dimensionality. In one limit, the non-equilibrium dynamical rules of these
      networks can generate scale-free networks with clustering and communities, in
      another limit planar random geometries with non-trivial modularity. Finally we
      find that these properties of the geometrical growing networks are present in a
      large set of real networks describing biological, social and technological
      systems. 

PMID- 25985282
TI  - The Mechanism of E-H (E = N, O) Bond Activation by a Germanium Corrole Complex: A
      Combined Experimental and Computational Study.
AB  - (TPFC)Ge(TEMPO) (1, TPFC = tris(pentafluorophenyl)corrole, TEMPO(*) = (2,2,6,6
      tetramethylpiperidin-1-yl)oxyl) shows high reactivity toward E-H (E = N, O) bond
      cleavage in R1R2NH (R1R2 = HH, (n)PrH, (i)Pr2, Et2, PhH) and ROH (R = H, CH3)
      under visible light irradiation. Electron paramagnetic resonance (EPR) analyses
      together with the density functional theory (DFT) calculations reveal the E-H
      bond activation by [(TPFC)Ge](0)(2)/TEMPO(*) radical pair, generated by
      photocleavage of the labile Ge-O bond in compound 1, involving two sequential
      steps: (i) coordination of substrates to [(TPFC)Ge](0) and (ii) E-H bond cleavage
      induced by TEMPO(*) through proton coupled electron transfer (PCET). 

PMID- 25985281
TI  - SMAD3 deficiency promotes vessel wall remodeling, collagen fiber reorganization
      and leukocyte infiltration in an inflammatory abdominal aortic aneurysm mouse
      model.
AB  - TGF-beta signaling plays critical roles in the pathogenesis of aneurysms;
      however, it is still unclear whether its role is protective or destructive. In
      this study, we investigate the role of SMAD3 in the pathogenesis of calcium
      chloride (CaCl2)-induced abdominal aortic aneurysms (AAA) in Smad3(-/-), Smad3(+/
      ) and Smad3(+/+) mice. We find that loss of SMAD3 drastically increases wall
      thickening of the abdominal aorta. Histological analyses show significant vessel
      wall remodeling with elastic fiber fragmentation. Remarkably, under polarized
      light, collagen fibers in the hyperplastic adventitia of Smad3(-/-) mice show
      extensive reorganization accompanied by loosely packed thin and radial collagen
      fibers. The expressions of matrix metalloproteinases including MMP2, MMP9, and
      MMP12 and infiltration of macrophage/T cells are drastically enhanced in the
      vascular wall of Smad3(-/-) mice. We also observe marked increase of NF-kappaB
      and ERK1/2 signaling as well as the expression of nuclear Smad2, Smad4 and TGF
      beta1 in the vessel wall of Smad3(-/-) mice. In addition, we find that SMAD3
      expression is reduced in the dedifferentiated medial smooth muscle-like cells of
      human AAA patients. These findings provide direct in vivo evidence to support the
      essential roles of SMAD3 in protecting vessel wall integrity and suppressing
      inflammation in the pathogenesis of AAAs. 

PMID- 25985283
TI  - Discovery of Selective Small-Molecule Inhibitors for the beta-Catenin/T-Cell
      Factor Protein-Protein Interaction through the Optimization of the Acyl Hydrazone
      Moiety.
AB  - Acyl hydrazone is an important functional group for the discovery of bioactive
      small molecules. This functional group is also recognized as a pan assay
      interference structure. In this study, a new small-molecule inhibitor for the
      beta-catenin/Tcf protein-protein interaction (PPI), ZINC02092166, was identified
      through AlphaScreen and FP assays. This compound contains an acyl hydrazone group
      and exhibits higher inhibitory activities in cell-based assays than biochemical
      assays. Inhibitor optimization resulted in chemically stable derivatives that
      disrupt the beta-catenin/Tcf PPI. The binding mode of new inhibitors was
      characterized by site-directed mutagenesis and structure-activity relationship
      studies. This series of inhibitors with a new scaffold exhibits dual selectivity
      for beta-catenin/Tcf over beta-catenin/cadherin and beta-catenin/APC PPIs. One
      derivative of this series suppresses canonical Wnt signaling, downregulates the
      expression of Wnt target genes, and inhibits the growth of cancer cells. This
      compound represents a solid starting point for the development of potent and
      selective beta-catenin/Tcf inhibitors. 

PMID- 25985285
TI  - Living better with dementia: strengths-based social work practice and dementia
      care.
AB  - This article first argues that quality of life is possible despite the onset of
      dementia in late life. It also demonstrates how core concepts of social work
      practice, such as family systems theory, the strengths perspective, and use of
      self, can be applied to practice with dementia-affected persons. In addition, it
      provides practical suggestions for supporting care partners in nurturing "we
      ness", focusing on what remains rather than was is lost, and remaining authentic.
      When strengths-based social work practice is integrated into dementia care
      protocols, wellbeing can increase. As a result, the more than 40 million persons
      worldwide who are affected by dementia do not have to resign themselves to the
      despair, devastation and inevitable demise of quality of life that dominate
      perception of the illness. 

PMID- 25985284
TI  - Moving toward integrated health: an opportunity for social work.
AB  - With the passage of the Patient Protection and Affordable Care Act (PPACA) and
      ongoing health care reform efforts, this is a critical time for the social work
      profession. The approaches and values embedded in health care reform are
      congruent with social work. One strategy is to improve care for people with co
      morbid and chronic illnesses by integrating primary care and behavioral health
      services. This paper defines integrated health and how the PPACA promotes
      integrated health care through system redesign and payment reform. We consider
      how social workers can prepare for health care reform and discuss the
      implications of these changes for the future of the profession. 

PMID- 25985286
TI  - Thinking big, supporting families and enabling coping: the value of social work
      in patient and family centered health care.
AB  - Patient and family-centered care has become a focus in health services. Social
      work has a rich history of providing responsive patient care. This study
      identified the contribution and value of social work to PFCC from the key
      stakeholder perspectives of health social workers (n = 65). Utilizing
      interpretive description, four themes emerged: (1) Thinking big and holistically,
      (2) Intervening with families, (3) Enabling patient and family coping, and (4)
      Maximizing hospital and community resources. Barriers included a lack of power,
      professional isolation and role creep. Implications for research and practice are
      provided. 

PMID- 25985287
TI  - The paradox of homeless youth pregnancy: a review of challenges and
      opportunities.
AB  - Compared to their housed counterparts, homeless youth become pregnant at
      exceptionally high rates. Causes of such pregnancies are multifaceted, while a
      paradoxically high proportion of these pregnancies are intended. This review
      discusses causes and risk factors associated with homeless youth pregnancies, and
      notes experiences of pregnancy decision-making discord, challenges encountered
      during and following pregnancy, and difficulties faced by homeless youth when or
      if they become parents. Because homeless youth face a wide array of unique risks,
      future research would benefit from exploring alternative approaches to prevention
      to reduce pregnancies and improve sexual and reproductive health outcomes among
      this population. 

PMID- 25985288
TI  - A Home-Based Intervention's Impact on Caregiver Burden for Veterans With
      Dependence Performing Activities of Daily Living: An Interdisciplinary Approach.
AB  - The Veterans Health Administration offers multiple programs to support veteran's
      caregivers. This study examines one such program, modeled after the national VHA
      Home Based Primary Care Program (HBPC). A retrospective secondary data analysis
      was conducted on the VHA GAP program, examining the impact on reducing caregiver
      burden. Findings from examination of 48 veteran/caregiver dyads indicated the
      program had a clinically and statistically significant impact on decreasing
      caregiver role strain. These findings were compared to the national evidence
      based HBPC program, finding no significant differences in decrease of caregiver
      burden between the recipients of the GAP program and the national HBPC programs. 

PMID- 25985289
TI  - The Unchecked HIV/AIDS Crisis in Mississippi.
AB  - While the population of the southern United States is only 37% of the country's
      total, this region is experiencing 50% of new HIV diagnoses and 46% of new AIDS
      diagnoses. Specifically, Mississippi has the highest rates of new infection, the
      most AIDS deaths, the greatest number of people living with HIV/AIDS, and the
      fewest resources. Mississippi has the highest death rate in the country: 32.9 per
      1,000. A Mississippian with HIV/AIDS is almost twice as likely to die as the
      average American with the virus (SHARP Report, 2010). Compounding the problem are
      government policy issues, such as disproportionate program funding; socio
      economic issues, such as widespread poverty, housing insecurity, and the lack of
      access to care; and cultural issues, such as homophobia and social stigma. These
      factors are reflected in this study which examines the needs of people living
      with HIV/AIDS in a southern, rural county of Mississippi. From a representative
      sample of 218 HIV positive individuals, researchers identified the levels of need
      for housing, transportation, medical care, mental health care, substance abuse
      treatment, and education. The author discusses the reciprocal influences of these
      needs and HIV, the need for policy changes at the state and federal levels, and
      the need for resources that both support people living with HIV/AIDS and curb the
      rate of new infections. 

PMID- 25985291
TI  - Predictors of reading comprehension ability in primary school-aged children who
      have pragmatic language impairment.
AB  - PURPOSE: Children who have pragmatic language impairment (CwPLI) have
      difficulties with the use of language in social contexts and show impairments in
      above-sentence level language tasks. Previous studies have found that typically
      developing children's reading comprehension (RC) is predicted by reading accuracy
      and spoken sentence level comprehension (SLC). This study explores the predictive
      ability of these factors and above-sentence level comprehension (ASLC) on RC
      skills in a group of CwPLI. METHOD: Sixty nine primary school-aged CwPLI
      completed a measure of RC along with measures of reading accuracy, spoken SLC and
      both visual (pictorially presented) and spoken ASLC tasks. RESULTS: Regression
      analyses showed that reading accuracy was the strongest predictor of RC. Visual
      ASLC did not explain unique variance in RC on top of spoken SLC. In contrast, a
      measure of spoken ASLC explained unique variance in RC, independent from that
      explained by spoken SLC. A regression model with nonverbal intelligence, reading
      accuracy, spoken SLC and spoken ASLC as predictors explained 74.2% of the
      variance in RC. CONCLUSIONS: Findings suggest that spoken ASLC may measure
      additional factors that are important for RC success in CwPLI and should be
      included in routine assessments for language and literacy learning in this group.

PMID- 25985290
TI  - Catchment legacies and time lags: a parsimonious watershed model to predict the
      effects of legacy storage on nitrogen export.
AB  - Nutrient legacies in anthropogenic landscapes, accumulated over decades of
      fertilizer application, lead to time lags between implementation of conservation
      measures and improvements in water quality. Quantification of such time lags has
      remained difficult, however, due to an incomplete understanding of controls on
      nutrient depletion trajectories after changes in land-use or management
      practices. In this study, we have developed a parsimonious watershed model for
      quantifying catchment-scale time lags based on both soil nutrient accumulations
      (biogeochemical legacy) and groundwater travel time distributions (hydrologic
      legacy). The model accurately predicted the time lags observed in an Iowa
      watershed that had undergone a 41% conversion of area from row crop to native
      prairie. We explored the time scales of change for stream nutrient concentrations
      as a function of both natural and anthropogenic controls, from topography to
      spatial patterns of land-use change. Our results demonstrate that the existence
      of biogeochemical nutrient legacies increases time lags beyond those due to
      hydrologic legacy alone. In addition, we show that the maximum concentration
      reduction benefits vary according to the spatial pattern of intervention, with
      preferential conversion of land parcels having the shortest catchment-scale
      travel times providing proportionally greater concentration reductions as well as
      faster response times. In contrast, a random pattern of conversion results in a
      1:1 relationship between percent land conversion and percent concentration
      reduction, irrespective of denitrification rates within the landscape. Our
      modeling framework allows for the quantification of tradeoffs between costs
      associated with implementation of conservation measures and the time needed to
      see the desired concentration reductions, making it of great value to decision
      makers regarding optimal implementation of watershed conservation measures. 

PMID- 25985292
TI  - Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit
      aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant alpha
      Synuclein.
AB  - Accumulating evidence suggests that deposition of neurotoxic alpha-synuclein
      aggregates in the brain during the development of neurodegenerative diseases like
      Parkinson's disease can be curbed by anti-aggregation strategies that either
      disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits
      anti-amyloid activity but the use of this polyphenol is limited owing to its
      instability. As chemical modifications in curcumin confiscate this limitation,
      such efforts are intensively performed to discover molecules with similar but
      enhanced stability and superior properties. This study focuses on the inhibitory
      effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin
      isoxazole and their derivatives against alpha-synuclein aggregation,
      fibrillization and toxicity. Employing biochemical, biophysical and cell based
      assays we discovered that curcumin pyrazole (3) and its derivative N-(3
      Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only
      arresting fibrillization and disrupting preformed fibrils but also preventing
      formation of A11 conformation in the protein that imparts toxic effects.
      Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating
      A53T mutant form of alpha-synuclein. These two analogues of curcumin described
      here may therefore be useful therapeutic inhibitors for the treatment of alpha
      synuclein amyloidosis and toxicity in Parkinson's disease and other
      synucleinopathies. 

PMID- 25985293
TI  - Dose rate properties of NIPAM-based x-ray CT polymer gel dosimeters.
AB  - In this work we investigate radiation dose rate dependencies of N
      isopropylacrylamide (NIPAM) based polymer gel dosimeters (PGDs) used in
      conjunction with x-ray computed tomography imaging for radiotherapy dose
      verification. We define four primary forms of dose rate variation: constant mean
      dose rate where beam on and beam off times both vary, variable mean dose rate
      where beam on time varies, variable mean dose rate where beam off time varies and
      machine dose rate (MU min(-1)). We utilize both small (20 mL) vials and large
      volume (1L) gel containers to identify and characterize dose rate dependence in
      NIPAM PGDs. Results indicate that all investigated constant and variable mean
      dose rates had negligible affect on PGD dose response with the exception of
      machine dose rates (100-600 MU min(-1)) which produced variations in dose
      response significantly lower than previously reported. Explanations of the
      reduced variability in dose response are given. It is also shown that NIPAM PGD
      dose response is not affected by variations in dose rate that may occur in
      modulated treatment deliveries. Finally, compositional changes in NIPAM PGDs are
      investigated as potential mitigating strategies for dose rate-dependent response
      variability.

PMID- 25985294
TI  - Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on
      cerebral oxygen kinetics.
AB  - BACKGROUND: The underlying neuro-protective mechanisms of antenatal magnesium
      sulfate (MgSO(4)) in infants born preterm remain poorly understood. Early
      neonatal brain injury may be preceded by low cerebral blood flow (CBF) and
      elevated cerebral fractional tissue oxygen extraction (cFTOE). This study
      investigated the effect of antenatal MgSO(4) on cerebral oxygen delivery,
      consumption, and cFTOE in preterm infants. METHODS: CBF and tissue oxygenation
      index were measured, and oxygen delivery, consumption, and cFTOE calculated
      within 24 h of birth and at 48 and 72 h of life in 36 infants <= 30 wk gestation
      exposed to MgSO(4) and 29 unexposed infants. RESULTS: Total internal carotid
      blood flow and cerebral oxygen delivery did not differ between the groups at the
      three study time-points. Cerebral oxygen consumption and cFTOE were lower in
      infants exposed to antenatal MgSO(4) (P = 0.012) compared to unexposed infants
      within 24 h of delivery. This difference was not evident by 48 h of age. Fewer
      infants in the MgSO(4) group developed P/IVH by 72 h of age (P = 0.03).
      CONCLUSION: Infants exposed to MgSO(4) had similar systemic and cerebral
      hemodynamics but lower cFTOE compared to nonexposed. These findings suggest
      reduced cerebral metabolism maybe a component of the neuro-protective actions of
      antenatal MgSO(4).

PMID- 25985295
TI  - An interesting radiological picture of post traumatic TMJ ankylosis due to
      sagittal condylar fracture.
AB  - INTRODUCTION: In a condylar fracture whether to intervene or to go for
      conservative management still remains a dilemma. Studies and hypothesis suggests
      that it's medially dislocated condylar fracture segment that is more likely to
      ankylose, moreover no consensus have been put forth as to whether to remove the
      medially displaced fracture segment. PRESENTATION OF CASE: The current article
      describes a case of unilateral temporomandibular joint (TMJ) ankylosis, which
      resulted as a sequlae from conservative management of a bilateral condylar
      fracture of which, the ankylosed side had a sagittal fracture of condyle. In our
      case the post trauma CT shows the lateral segment abutting with the arch and that
      the area has become ankylotic in a span of 2 years. Here we report a case of
      posttraumatic unilateral TMJ ankylosis resulting from closed reduction of a
      bilateral condylar fracture with interesting radiological findings. DISCUSSION:
      We have tried to discuss a rather interesting radiological picture of
      posttraumatic TMJ ankylosis which resulted as a sequlae from conservative
      management of a bilateral condylar fracture. CONCLUSION: The dilemma for a
      clinician as to whether to intervene in a condylar fracture or to go for
      conservative management still remains at large. As in this case the medial
      fracture segment was intact and the lateral segment was resulting in ankylosis.

PMID- 25985296
TI  - Perforated appendix with abscess: Immediate or interval appendectomy? Some
      examples to explain our choice.
AB  - INTRODUCTION: There are no clear guidelines in the treatment of a perforated
      appendicitis associated with periappendiceal abscess without generalized
      peritonitis. PRESENTATION OF CASES: We retrospectively studied six examples of
      treated children in order to discuss the reasons of our team's therapeutic
      approach. Some children were treated with a conservative antibiotic therapy to
      solve acute abdomen pain, planning a routine interval appendectomy after some
      months. Others, instead, underwent an immediate appendectomy. DISCUSSION: By
      examining these examples we wanted to highlight how the first approach may be
      associated with shorter surgery time, fewer overall hospital days, faster
      refeeding and minor complications. CONCLUSION: Our team's therapeutic choice, in
      the case of a perforated appendicitis with an abscess and coprolith is an initial
      conservative case management followed by a routine interval appendectomy
      performed not later than 4 months after discharge.

PMID- 25985297
TI  - Accessory spleen in the pelvis: A case report.
AB  - INTRODUCTION: Accessory Spleen (AS) is a very rare entity and usually near the
      spleen's hilum and in the tail of the pancreas. Pelvis reported as an atypical
      and a rare localization. AS may be formed during embryonic life, they rise from
      the left side of the dorsal mesogastrium as a result of imperfect fusion of
      separate splenic masses. PRESENTATION OF CASE: We report a case of an AS
      presenting as an left adnexal mass in a middle-aged woman. Transvaginal
      ultrasonography and magnetic resonance imaging (MRI) revealed a left adnexial
      mass. Laparatomy was performed, and histological examination revealed that
      resected mass was splenic tissue. DISCUSSION: An AS is an incidental finding of
      no clinical significance in most patients. AS are generally determined during
      radiological investigations or during open or laparoscopic surgeries. When, the
      AS settle in the adnexal area; the differential diagnosis could include the
      causes of adnexal masses like enlarged lymph nodes, subserous fibroid, ovarian
      tumors, organized hematoma, tuboovarian abscess. CONCLUSION: Althought pelvic
      accessory spleen is a rare condition, should be considered in the differential
      diagnosis of adnexal masses.

PMID- 25985298
TI  - In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal
      Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused
      by Acid-Reducing Agents.
AB  - Weakly basic drugs typically exhibit pH-dependent solubility in the physiological
      pH range, displaying supersaturation or precipitation along the gastrointestinal
      tract. Additionally, their oral bioavailabilities may be affected by
      coadministration of acid-reducing agents that elevate gastric pH. The purpose of
      this study was to assess the feasibility of a multicompartmental in vitro
      dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo
      dissolution of certain oral medications. In vitro dissolution studies of
      fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class
      IIb), were performed in the GIS as well as United States Pharmacopeia (USP)
      apparatus II and compared with the results of clinical drug-drug interaction
      (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved
      within 60 min regardless of pH, reflecting no DDI between fluconazole and acid
      reducing agents in a clinical study. On the other hand, seven-fold and 15-fold
      higher concentrations of dipyridamole than saturation solubility were observed in
      the intestinal compartments in GIS with gastric pH 2.0. Precipitation of
      dipyridamole was also observed in the GIS, and the percentage of dipyridamole in
      solution was 45.2 +/- 7.0%. In GIS with gastric pH 6.0, mimicking the
      coadministration of acid-reducing agents, the concentration of dipyridamole was
      equal to its saturation solubility, and the percentage of drug in solution was
      9.3 +/- 2.7%. These results are consistent with the clinical DDI study of
      dipyridamole with famotidine, which significantly reduced the Cmax and area under
      the curve. An In situ mouse infusion study combined with GIS revealed that high
      concentration of dipyridamole in the GIS enhanced oral drug absorption, which
      confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be
      a useful apparatus to predict in vivo dissolution for BCS class IIb drugs. 

PMID- 25985299
TI  - Oxygen concentration controls epigenetic effects in models of familial
      paraganglioma.
AB  - Familial paraganglioma (PGL) is a rare neuroendocrine cancer associated with
      defects in the genes encoding the subunits of succinate dehydrogenase (SDH), a
      tricarboxylic acid (TCA) cycle enzyme. For unknown reasons, a higher prevalence
      of PGL has been reported for humans living at higher altitude, with increased
      disease aggressiveness and morbidity. In this study, we evaluate the effects of
      oxygen on epigenetic changes due to succinate accumulation in three SDH loss cell
      culture models. We test the hypothesis that the mechanism of alpha-ketoglutarate
      (alpha-KG)-dependent dioxygenase enzymes explains the inhibitory synergy of
      hypoxia and succinate accumulation. We confirm that SDH loss leads to profound
      succinate accumulation. We further show that hypoxia and succinate accumulation
      synergistically inhibit alpha-KG-dependent dioxygenases leading to increased
      stabilization of transcription factor HIF1alpha, HIF2alpha, and hypermethylation
      of histones and DNA. Increasing oxygen suppresses succinate inhibition of alpha
      KG-dependent dioxygenases. This result provides a possible explanation for the
      association between hypoxia and PGL, and suggests hyperoxia as a potential novel
      therapy. 

PMID- 25985301
TI  - Ongoing Processes in a Fitness Network Model under Restricted Resources.
AB  - In real networks, the resources that make up the nodes and edges are finite. This
      constraint poses a serious problem for network modeling, namely, the
      compatibility between robustness and efficiency. However, these concepts are
      generally in conflict with each other. In this study, we propose a new fitness
      driven network model for finite resources. In our model, each individual has its
      own fitness, which it tries to increase. The main assumption in fitness-driven
      networks is that incomplete estimation of fitness results in a dynamical growing
      network. By taking into account these internal dynamics, nodes and edges emerge
      as a result of exchanges between finite resources. We show that our network model
      exhibits exponential distributions in the in- and out-degree distributions and a
      power law distribution of edge weights. Furthermore, our network model resolves
      the trade-off relationship between robustness and efficiency. Our result suggests
      that growing and anti-growing networks are the result of resolving the trade-off
      problem itself. 

PMID- 25985300
TI  - Comparative Transcriptome Analysis between the Cytoplasmic Male Sterile Line
      NJCMS1A and Its Maintainer NJCMS1B in Soybean (Glycine max (L.) Merr.).
AB  - BACKGROUND: The utilization of soybean heterosis is probably one of the potential
      approaches in future yield breakthrough as was the situation in rice breeding in
      China. Cytoplasmic male sterility (CMS) plays an important role in the production
      of hybrid seeds. However, the molecular mechanism of CMS in soybean remains
      unclear. RESULTS: The comparative transcriptome analysis between cytoplasmic male
      sterile line NJCMS1A and its near-isogenic maintainer NJCMS1B in soybean was
      conducted using Illumina sequencing technology. A total of 88,643 transcripts
      were produced in Illumina sequencing. Then 56,044 genes were obtained matching
      soybean reference genome. Three hundred and sixty five differentially expressed
      genes (DEGs) between NJCMS1A and NJCMS1B were screened by threshold, among which,
      339 down-regulated and 26 up-regulated in NJCMS1A compared to in NJCMS1B. Gene
      Ontology (GO) annotation showed that 242 DEGs were annotated to 19 functional
      categories. Clusters of Orthologous Groups of proteins (COG) annotation showed
      that 265 DEGs were classified into 19 categories. Kyoto Encyclopedia of Genes and
      Genomes (KEGG) analysis showed that 46 DEGs were assigned to 33 metabolic
      pathways. According to functional and metabolic pathway analysis combined with
      reported literatures, the relations between some key DEGs and the male sterility
      of NJCMS1A were discussed. qRT-PCR analysis validated that the gene expression
      pattern in RNA-Seq was reliable. Finally, enzyme activity assay showed that
      energy supply was decreased in NJCMS1A compared to in NJCMS1B. CONCLUSIONS: We
      concluded that the male sterility of NJCMS1A might be related to the disturbed
      functions and metabolism pathways of some key DEGs, such as DEGs involved in
      carbohydrate and energy metabolism, transcription factors, regulation of pollen
      development, elimination of reactive oxygen species (ROS), cellular signal
      transduction, and programmed cell death (PCD) etc. Future research will focus on
      cloning and transgenic function validation of possible candidate genes associated
      with soybean CMS.

PMID- 25985303
TI  - Production of mono- and di-carboxylated polyethylene glycols as a factor obstacle
      to the successful ozonation-assisted biodegradation of ethoxylated compounds.
AB  - Ozonation is believed to improve the biodegradability of organic compounds. In
      the present study, degradation of nonylphenol ethoxylates (NPEOs) was monitored
      in hybrid treatment systems consisting of ozonation and microbial degradation
      processes. We found that ozonation of NPEOs decreased, rather than increased, the
      biodegradability under certain conditions. The timing of ozonation was a
      definitive factor in determining whether ozonation increased or decreased the
      biodegradation rates of NPEOs. Initial ozonation of NPEOs prior to biodegradation
      reduced the rate of dissolved organic carbon (DOC) removal during the subsequent
      14 d of biodegradation, whereas intermediate ozonation at the 9th day of
      biodegradation improved subsequent DOC removal during 14 d of NPEO
      biodegradation. Furthermore, reduction of DOC removal was also observed, when
      initial ozonation prior to biodegradation was subjected to cetyl alcohol
      ethoxylates. The production of less biodegradable intermediates, such as mono-
      and dicarboxylated polyethylene glycols (MCPEGs and DCPEGs), was responsible for
      the negative effect of ozonation on biodegradability of NPEOs. DCPEGs and MCPEGs
      were produced by biodegradation of polyethylene glycols (PEGs) that were
      ozonolysis products of the NPEOs, and the biodegradability of DCPEGs and MCPEGs
      was less than that of the precursor PEGs. The results indicate that, if the
      target chemicals contain ethoxy chains, production of PEGs may be one of the
      important factors when ozonation is considered.

PMID- 25985302
TI  - The Arabidopsis KH-Domain RNA-Binding Protein ESR1 Functions in Components of
      Jasmonate Signalling, Unlinking Growth Restraint and Resistance to Stress.
AB  - Glutathione S-transferases (GSTs) play important roles in the protection of cells
      against toxins and oxidative damage where one Arabidopsis member, GSTF8, has
      become a commonly used marker gene for early stress and defense responses. A
      GSTF8 promoter fragment fused to the luciferase reporter gene was used in a
      forward genetic screen for Arabidopsis mutants with up-regulated GSTF8 promoter
      activity. This identified the esr1-1 (enhanced stress response 1) mutant which
      also conferred increased resistance to the fungal pathogen Fusarium oxysporum.
      Through positional cloning, the ESR1 gene was found to encode a KH-domain
      containing RNA-binding protein (At5g53060). Whole transcriptome sequencing of
      esr1-1 identified altered expression of genes involved in responses to biotic and
      abiotic stimuli, hormone signaling pathways and developmental processes. In
      particular was an overall significant enrichment for jasmonic acid (JA) mediated
      processes in the esr1-1 down-regulated dataset. A subset of these genes were
      tested for MeJA inducibility and we found the expression of some but not all were
      reduced in esr1-1. The esr1-1 mutant was not impaired in other aspects of JA
      signalling such as JA- sensitivity or development, suggesting ESR1 functions in
      specific components of the JA-signaling pathway. Examination of salicylic acid
      (SA) regulated marker genes in esr1-1 showed no increase in basal or SA induced
      expression suggesting repression of JA-regulated genes is not due to antagonistic
      SA-JA crosstalk. These results define new roles for KH-domain containing proteins
      with ESR1 unlinking JA-mediated growth and defense responses. 

PMID- 25985304
TI  - Ionic liquid biodegradability depends on specific wastewater microbial consortia.
AB  - Complete biodegradation of a newly-synthesized chemical in a wastewater treatment
      plant (WWTP) eliminates the potential for novel environmental pollutants.
      However, differences within- and between-WWTP microbial communities may alter
      expectations for biodegradation. WWTP communities can also serve as a source of
      unique consortia that, when enriched, can metabolize chemicals that tend to
      resist degradation, but are otherwise promising green alternatives. We tested the
      biodegradability of three ionic liquids (ILs): 1-octyl-3-methylpyridinium bromide
      (OMP), 1-butyl-3-methylpyridinium bromide (BMP) and 1-butyl-3-methylimidazolium
      chloride (BMIM). We performed tests using communities from two WWTPs at three
      time points. Site-specific and temporal variation both influenced community
      composition, which impacted the success of OMP biodegradability. Neither BMP nor
      BMIM degraded in any test, suggesting that these ILs are unlikely to be removed
      by traditional treatment. Following standard biodegradation assays, we enriched
      for three consortia that were capable of quickly degrading OMP, BMP and BMIM. Our
      results indicate WWTPs are not functionally redundant with regard to
      biodegradation of specific ionic liquids. However, consortia can be enriched to
      degrade chemicals that fail biodegradability assays. This information can be used
      to prepare pre-treatment procedures and prevent environmental release of novel
      pollutants. 

PMID- 25985306
TI  - Correction: Natural epigenetic polymorphisms lead to intraspecific variation in
      Arabidopsis gene imprinting.

PMID- 25985305
TI  - Redox proteomics of the inflammatory secretome identifies a common set of
      redoxins and other glutathionylated proteins released in inflammation, influenza
      virus infection and oxidative stress.
AB  - Protein cysteines can form transient disulfides with glutathione (GSH), resulting
      in the production of glutathionylated proteins, and this process is regarded as a
      mechanism by which the redox state of the cell can regulate protein function.
      Most studies on redox regulation of immunity have focused on intracellular
      proteins. In this study we have used redox proteomics to identify those proteins
      released in glutathionylated form by macrophages stimulated with
      lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of
      the several proteins identified in the redox secretome, we have selected a number
      for validation. Proteomic analysis indicated that LPS stimulated the release of
      peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1
      (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is
      glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary
      epithelial cell line, A549, infected with influenza virus. The release of the
      proteins identified was inhibited by the anti-inflammatory glucocorticoid,
      dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-alpha
      release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N
      acetylcysteine (NAC), which did not affect TNF-alpha production. The proteins
      identified could be useful as biomarkers of oxidative stress associated with
      inflammation, and further studies will be required to investigate if the
      extracellular forms of these proteins has immunoregulatory functions. 

PMID- 25985307
TI  - Dog-assisted therapies and activities in rehabilitation of children with cerebral
      palsy and physical and mental disabilities.
AB  - The aim of the present study was to evaluate dog-assisted therapies and
      activities in the rehabilitation of children with cerebral palsy and physical and
      mental disabilities who have difficulties in benefiting from well-being and
      health-improving services. This descriptive-explanatory study was conducted in
      disabled children of various ages between 2008 and 2011 by an experienced team in
      a private training and rehabilitation center in Antalya (Turkey). In this study,
      five study groups were formed among the children with physical and mental
      disabilities. During the therapy studies, three dogs were used. For each therapy
      group, the goals for the children and therapist were defined, and the activities
      were determined according to these goals. The entire study process was followed
      using audio-records and photographs of patients. The expected targets were
      reached in all study groups. The children who experienced fear, anxiety and
      difficulties due to their disabilities in daily life learned to cope with their
      anxieties and fears, set goals and make plans to achieve their aims. During this
      study, the children improved their abilities to use their bodies according to
      their capabilities. Accordingly, they improved their ability to develop empathy
      between themselves and a therapy dog, to receive and present help, and to
      communicate. The results of the present study revealed that dog-assisted
      therapies and activities can be a supportive method for routine treatment
      procedures in the rehabilitation of children with cerebral palsy and physical and
      mental disabilities. 

PMID- 25985308
TI  - Effect of naturally occurring ozone air pollution episodes on pulmonary oxidative
      stress and inflammation.
AB  - This study aimed to determine if naturally occurring episodes of ozone air
      pollution in the Salt Lake Valley in Utah, USA, during the summer are associated
      with increased pulmonary inflammation and oxidative stress, increased respiratory
      symptoms, and decreased lung function in individuals with chronic obstructive
      pulmonary disease (COPD) compared to controls. We measured biomarkers
      (nitrite/nitrate (NOx), 8-isoprostane) in exhaled breath condensate (EBC),
      spirometry, and respiratory symptoms in 11 former smokers with moderate-to-severe
      COPD and nine former smokers without airflow obstruction during periods of low
      and high ozone air pollution. High ozone levels were associated with increased
      NOx in EBC in both COPD (8.7 (+/-8.5) vs. 28.6 (+/-17.6) MUmol/L on clean air vs.
      pollution days, respectively, p < 0.01) and control participants (7.6 (+/-16.5)
      vs. 28.5 (+/-15.6) MUmol/L on clean air vs. pollution days, respectively, p =
      0.02). There was no difference in pollution effect between COPD and control
      groups, and no difference in EBC 8-isoprostane, pulmonary function, or
      respiratory symptoms between clean air and pollution days in either group. Former
      smokers both with and without airflow obstruction developed airway oxidative
      stress and inflammation in association with ozone air pollution episodes. 

PMID- 25985309
TI  - Characterization and Cytotoxicity of PM<0.2, PM0.2-2.5 and PM2.5-10 around MSWI
      in Shanghai, China.
AB  - BACKGROUND: The potential impact of municipal solid waste incineration (MSWI),
      which is an anthropogenic source of aerosol emissions, is of great public health
      concern. This study investigated the characterization and cytotoxic effects of
      ambient ultrafine particles (PM<0.2), fine particles (PM0.2-2.5) and coarse
      particles (PM2.5-10) collected around a municipal solid waste incineration (MSWI)
      plant in the Pudong district of Shanghai. METHODS: Mass concentrations of trace
      elements in particulate matter (PM) samples were determined using ICP-MS
      (Inductively Coupled Plasma Mass Spectrometry). The cytotoxicity of sampled
      atmospheric PM was evaluated by cell viability and reactive oxygen species (ROS)
      levels in A549 cells. RESULT: The mass percentage of PM0.2-2.5 accounted for
      72.91% of the total mass of PM. Crustal metals (Mg, Al, and Ti) were abundant in
      the coarse particles, while the anthropogenic elements (V, Ni, Cu, Zn, Cd, and
      Pb) were dominant in the fine particles. The enrichment factors of Zn, Cd and Pb
      in the fine and ultrafine particles were extremely high (>100). The cytotoxicity
      of the size-resolved particles was in the order of coarse particles < fine
      particles < ultrafine particles. CONCLUSIONS: Fine particles dominated the MSWI
      ambient particles. Emissions from the MSWI could bring contamination of
      anthropogenic elements (Zn, Cd and Pb) into ambient environment. The PM around
      the MSWI plant displayed an additive toxic effect, and the ultrafine and fine
      particles possessed higher biological toxicity than the coarse particles.

PMID- 25985310
TI  - Prevalence of mental disorders in 6-16-year-old students in Sichuan province,
      China.
AB  - To investigate the point prevalence of mental disorders in school students,
      multistage cluster stratified random sampling and two-phase survey methods were
      used to identify 40 primary and middle schools. The students were screened using
      the Chinese version of the Child Behavior Checklist and diagnosed using the Mini
      International Neuropsychiatric Interview. The prevalence of behavioral problems
      was 19.13%. The prevalence of behavioral problems significantly differed by sex,
      age, city of residence, and caretaker. The six-month prevalence of any mental
      disorder was 15.24% (95% CI: 15.49%-16.97%). Psychiatric disorders were more
      prevalent in boys (17.33%) relative to girls (13.11%; p < 0.01). The prevalence
      of mental disorders significantly differed by community and caretaker, and 36.46%
      of students exhibited comorbidity. Results demonstrated important mental health
      issues, with a high incidence of comorbidities, in this population. Students'
      mental health requires increased attention, particularly in poverty-stricken
      areas and left-behind children and adolescents. 

PMID- 25985311
TI  - Identification, characterization and antibiotic resistance of bacterial isolates
      obtained from waterpipe device hoses.
AB  - The general lack of knowledge about the health effects of waterpipe smoking is
      among the reasons for its global spread. In this study, bacterial contamination
      of waterpipe hoses was investigated. Twenty hoses were collected from waterpipe
      cafes and screened for bacterial pathogens using standard culture and isolation
      techniques. Additionally, resistance of isolated bacteria to common antibiotics
      was determined by identifying the minimum inhibitory concentration (MIC) of each
      isolate. Forty eight bacterial isolates were detected. Isolates included both
      Gram-positive and Gram-negative pathogens from species that included Micrococcus
      (12), Corynebacterium (13) and Bacillus (9). In addition, some of the detected
      pathogens were found to be resistant to aztreonam (79%), cefixime (79%),
      norfloxacin, amoxicillin (47%), clarithromycin (46%) and enrofloxacin (38%). In
      conclusion, the hose of the waterpipe device is a good environment for the growth
      of bacterial pathogens, which can then be transmitted to users. 

PMID- 25985312
TI  - Exposure monitoring and risk assessment of biphenyl in the workplace.
AB  - This study was performed to assess exposure to and the risk caused by biphenyl in
      the workplace. Biphenyl is widely used as a heat transfer medium and as an
      emulsifier and polish in industry. Vapor or high levels of dust inhalation and
      dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory
      organs, and permanent lesions in the liver and nervous system. In this study, the
      workplace environment concentrations were assessed as central tendency exposure
      and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m3,
      respectively. In addition, the carcinogenic risk of biphenyl as determined by
      risk assessment was 0.14 * 10-4 (central tendency exposure) and 0.56 * 10-4
      (reasonable maximum exposure), which is below the acceptable risk value of 1.0 *
      10-4. Furthermore, the central tendency exposure and reasonable maximum exposure
      hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for
      inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively,
      which are all lower than the acceptable hazard quotient of 1.0. Therefore,
      exposure to biphenyl was found to be safe in current workplace environments.
      Because occupational exposure limits are based on socioeconomic assessment, they
      are generally higher than true values seen in toxicity experiments. Based on the
      results of exposure monitoring of biphenyl, the current occupational exposure
      limits in Korea could be reviewed.

PMID- 25985313
TI  - Trend of Suicide Rates According to Urbanity among Adolescents by Gender and
      Suicide Method in Korea, 1997-2012.
AB  - This study aims to quantifiably evaluate the trend of the suicide rate among
      Korean adolescents from 1997 to 2012 according to urbanity. We used national
      death certificates and registration population data by administrative district
      for 15-19 years-old adolescents. The annual percent change (APC) and average
      annual percent change (AAPC) were estimated by the Joinpoint Regression Program.
      The suicide rate in the rural areas was higher than that in the urban areas in
      both genders (males (/100,000), 12.2 vs. 8.5; females (/100,000), 10.2 vs. 7.4 in
      2012). However, the trend significantly increased only in the urban area (AAPC
      [95% CI]: males 2.6 [0.7, 4.6], females 3.3 [1.4, 5.2]). In urban areas, the
      suicide rate by jumping significantly increased in both genders (AAPC [95% CI]:
      males, 6.7 [4.3, 9.1]; females, 4.5 [3.0, 6.1]). In rural areas, the rate by self
      poisoning significantly decreased by 7.9% per year for males (95% CI: -12.5, 
      3.0) and the rate by hanging significantly increased by 10.1% per year for
      females (95% CI: 2.6, 18.2). The trend and methods of suicide differ according to
      urbanity; therefore, a suicide prevention policy based on urbanity needs to be
      established for adolescents in Korea. 

PMID- 25985316
TI  - Traumatic Brain Injury Patients With a Glasgow Coma Scale Score of <=8, Cerebral
      Edema, and/or a Basal Skull Fracture are More Susceptible to Developing
      Hyponatremia.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a common injury treated at the
      neurosurgery department. The incidence rate is approximately 3% in the general
      population and the mortality rate is 25%. The incidence of hyponatremia following
      TBI is 33%. Hyponatremia is one of the main causes of disability and/or death in
      TBI patients. This study investigated the epidemiology of hyponatremia following
      TBI. METHODS: Patients who were admitted to our hospital with moderate or severe
      TBI were analyzed retrospectively. The relationship between the occurrence of
      hyponatremia and age, sex, type of injury, Glasgow coma scale (GCS) score,
      whether the patient underwent surgery, and the presence of cerebral edema and
      basal skull fracture was analyzed statistically using a chi2 test and
      multivariate logistic regression analysis. RESULTS: Out of the 136 patients
      recruited for the study (81 males and 55 females; mean+/-SD age of 48+/-13 y), 56
      suffered from hyponatremia (ie, serum sodium level <135 mmol/L). Univariate
      analysis indicated that hyponatremia following TBI was not related to age
      (P>0.05), sex (P=0.347), or surgical history (P=0.492) but that it was related to
      the type of injury (P=0.031), a GCS score <=8 (P<0.001), the presence of cerebral
      edema (P<0.001), and/or a basal skull fracture (P<0.001). Multivariate logistic
      regression analysis confirmed a strong association between the occurrence of
      hyponatremia and a GCS score <=8 (P<0.016), the presence of cerebral edema
      (P<0.001), and a basal skull fracture (P<0.001). CONCLUSIONS: TBI patients with a
      GCS score <=8, cerebral edema, and/or a basal skull fracture are particularly
      prone to developing hyponatremia. These patients require additional treatment
      that should entail the normalization of serum sodium levels to prevent
      deterioration of their condition.

PMID- 25985314
TI  - Integrated assessment of artisanal and small-scale gold mining in Ghana--part 1:
      human health review.
AB  - This report is one of three synthesis documents produced via an integrated
      assessment (IA) that aims to increase understanding of artisanal and small-scale
      gold mining (ASGM) in Ghana. Given the complexities surrounding ASGM, an IA
      framework was utilized to analyze economic, social, health, and environmental
      data, and co-develop evidence-based responses with pertinent stakeholders. The
      current analysis focuses on the health of ASGM miners and community members, and
      synthesizes extant data from the literature as well as co-authors' recent
      findings regarding the causes, status, trends, and consequences of ASGM in Ghana.
      The results provide evidence from across multiple Ghanaian ASGM sites that
      document relatively high exposures to mercury and other heavy metals,
      occupational injuries and noise exposure. The work also reviews limited data on
      psychosocial health, nutrition, cardiovascular and respiratory health, sexual
      health, and water and sanitation. Taken together, the findings provide a thorough
      overview of human health issues in Ghanaian ASGM communities. Though more
      research is needed to further elucidate the relationships between ASGM and health
      outcomes, the existing research on plausible health consequences of ASGM should
      guide policies and actions to better address the unique challenges of ASGM in
      Ghana and potentially elsewhere. 

PMID- 25985317
TI  - Effect of Carbon Coating on the Physicochemical and Electrochemical Properties of
      Fe2O3 Nanoparticles for Anode Application in High Performance Lithium Ion
      Batteries.
AB  - Nanoparticulate Fe2O3 and Fe2O3/C composites with different carbon proportions
      have been prepared for anode application in lithium ion batteries (LIBs).
      Morphological studies revealed that particles of Fe2O3 in the composites were
      well-dispersed in the matrix of amorphous carbon. The properties of the gamma
      Fe2O3 nanoparticles and the correlation with the particle size and connectivity
      were studied by electron paramagnetic resonance, magnetic, and Mossbauer
      measurements. The electrochemical study revealed that composites with carbon have
      promising electrochemical performances. These samples yielded specific discharge
      capacities of 1200 mAh/g after operating for 100 cycles at 1C. These excellent
      results could be explained by the homogeneity of particle size and structure as
      well as the uniform distribution of gamma-Fe2O3 nanoparticles in the in situ
      generated amorphous carbon matrix. 

PMID- 25985315
TI  - Resistance of Stenotrophomonas maltophilia to Fluoroquinolones: Prevalence in a
      University Hospital and Possible Mechanisms.
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical distribution
      and genotyping of Stenotrophomonas maltophilia, its resistance to antimicrobial
      agents, and the possible mechanisms of this drug resistance. METHODS: S.
      maltophilia isolates were collected from clinical specimens in a university
      hospital in Northwestern China during the period between 2010 and 2012, and were
      identified to the species level with a fully automated microbiological system.
      Antimicrobial susceptibility testing was performed for S. maltophilia with the
      Kirby-Bauer disc diffusion method. The minimal inhibitory concentrations (MICs)
      of norfloxacin, ofloxacin, chloramphenicol, minocycline, ceftazidime,
      levofloxacin and ciprofloxacin against S. maltophilia were assessed using the
      agar dilution method, and changes in the MIC of norfloxacin, ciprofloxacin and
      ofloxacin were observed after the addition of reserpine, an efflux pump
      inhibitor. Fluoroquinolone resistance genes were detected in S. maltophilia using
      a polymerase chain reaction (PCR) assay, and the expression of efflux pump smeD
      and smeF genes was determined using a quantitative fluorescent (QF)-PCR assay.
      Pulsed-field gel electrophoresis (PFGE) was employed to genotype identified S.
      maltophilia isolates. RESULTS: A total of 426 S. maltophilia strains were
      isolated from the university hospital from 2010 to 2012, consisting of 10.1% of
      total non-fermentative bacteria. The prevalence of norfloxacin, ciprofloxacin and
      ofloxacin resistance was 32.4%, 21.9% and 13.2% in the 114 S. maltophilia
      isolates collected from 2012, respectively. Following reserpine treatment, 19 S.
      maltophilia isolates positive for efflux pump were identified, and high
      expression of smeD and smeF genes was detected in two resistant isolates. gyrA,
      parC, smeD, smeE and smeF genes were detected in all 114 S. maltophilia isolates,
      while smqnr gene was found in 25.4% of total isolates. Glu-Lys mutation (GAA-AAA)
      was detected at the 151th amino acid of the gyrA gene, while Gly-Arg mutation
      (GGC-CGC) was found at the 37th amino acid of the parC gene. However, no
      significant difference was observed in the prevalence of gyrA or parC mutation
      between fluoroquinolone-resistant and -susceptible isolates (p> 0.05). The smqnr
      gene showed 92% to 99% heterogenicity among the 14 S. maltophilia clinical
      isolates. PFGE of 29 smqnr gene-positive S. maltophilia clinical isolates
      revealed 25 PFGE genotypes and 28 subgenotypes. CONCLUSIONS: Monitoring the
      clinical distribution and antimicrobial resistance of S. maltophilia is of great
      significance for the clinical therapy of bacterial infections. Reserpine is
      effective to inhibit the active efflux of norfloxacin, ciprofloxacin and
      ofloxacin on S. maltophilia and reduce MIC of fluoroquinolones against the
      bacteria. The expression of efflux pump smeD and smeF genes correlates with the
      resistance of S. maltophilia to fluoroquinolones.

PMID- 25985318
TI  - MRI Inner Ear Imaging and Tone Burst Electrocochleography in the Diagnosis of
      Meniere's Disease.
AB  - OBJECTIVE: To compare the sensitivity of gadolinium MRI inner imaging with tone
      burst electrocochleography (EcochG) for diagnosing endolymphatic hydrops. STUDY
      DESIGN: A prospective study on patients who were to have an MRI scan to exclude
      retrocochlear pathology. SETTING: Tertiary care center. PATIENTS: One hundred and
      two patients: 57 patients with Possible, Probable, or Definite Meniere's Disease,
      25 with asymmetrical hearing loss, 18 with sudden sensorineural hearing loss, and
      2 with unilateral tinnitus had additional MRI inner ear imaging and click and
      tone burst stimulus EcochG testing. INTERVENTION: Diagnostic. MAIN OUTCOME
      MEASURE: To compare the sensitivity of the two techniques. RESULTS: In 30
      patients with symptom-based Definite Meniere's Disease, tone burst EcochG was
      positive in 25 (83%) and the click EcochG was positive in 9/30 (30%), and
      gadolinium MRI imaging diagnosed hydrops in 14 (47%). A positive result for
      either MRI imaging or tone burst EcochG was seen in 26 patients (87%). In 14
      subjects with symptom-based Probable Meniere's Disease, 10 (71%) had either a
      positive EcochG or MRI. In 13 with Possible Meniere's Disease, four (31%) had a
      positive EcochG or MRI. CONCLUSION: This study confirms the greatly enhanced
      diagnostic sensitivity of tone burst EcochG over click response in diagnosing
      endolymphatic hydrops in Meniere's disease. Even though adequate MRI imaging was
      achieved in 90%, tone burst EcochG was a more sensitive test.

PMID- 25985319
TI  - Giant Cell Reparative Granuloma of the Temporal Bone Treated With Calcitonin--10
      Years on.

PMID- 25985320
TI  - The Effect of Primary Care Provider Turnover on Patient Experience of Care and
      Ambulatory Quality of Care.
AB  - IMPORTANCE: Primary care provider (PCP) turnover is common and can disrupt
      patient continuity of care. Little is known about the effect of PCP turnover on
      patient care experience and quality of care. OBJECTIVE: To measure the effect of
      PCP turnover on patient experiences of care and ambulatory care quality. DESIGN,
      SETTING, AND PARTICIPANTS: Observational, retrospective cohort study of a
      nationwide sample of primary care patients in the Veterans Health Administration
      (VHA). We included all patients enrolled in primary care at the VHA between 2010
      and 2012 included in 1 of 2 national data sets used to measure our outcome
      variables: 326,374 patients in the Survey of Healthcare Experiences of Patients
      (SHEP; used to measure patient experience of care) associated with 8441 PCPs and
      184,501 patients in the External Peer Review Program (EPRP; used to measure
      ambulatory care quality) associated with 6973 PCPs. EXPOSURES: Whether a patient
      experienced PCP turnover, defined as a patient whose provider (physician, nurse
      practitioner, or physician assistant) had left the VHA (ie, had no patient
      encounters for 12 months). MAIN OUTCOMES AND MEASURES: Five patient care
      experience measures (from SHEP) and 11 measures of quality of ambulatory care
      (from EPRP). RESULTS: Nine percent of patients experienced a PCP turnover in our
      study sample. Primary care provider turnover was associated with a worse rating
      in each domain of patient care experience. Turnover was associated with a reduced
      likelihood of having a positive rating of their personal physician of 68.2% vs
      74.6% (adjusted percentage point difference, -5.3; 95% CI, -6.0 to -4.7) and a
      reduced likelihood of getting care quickly of 36.5% vs 38.5% (adjusted percentage
      point difference, -1.1; 95% CI, -2.1 to -0.1). In contrast, PCP turnover was not
      associated with lower quality of ambulatory care except for a lower likelihood of
      controlling blood pressure of 78.7% vs 80.4% (adjusted percentage point
      difference, -1.44; 95% CI, -2.2 to -0.7). In 9 measures of ambulatory care
      quality, the difference between patients who experienced no PCP turnover and
      those who had a PCP turnover was less than 1 percentage point. These effects were
      moderated by the patients' continuity with their PCP prior to turnover, with a
      larger detrimental effect of PCP turnover among those with higher continuity
      prior to the turnover. CONCLUSIONS AND RELEVANCE: Primary care provider turnover
      was associated with worse patient experiences of care but did not have a major
      effect on ambulatory care quality.

PMID- 25985322
TI  - Genome Engineering in Cyanobacteria: Where We Are and Where We Need To Go.
AB  - Genome engineering of cyanobacteria is a promising area of development in order
      to produce fuels, feedstocks, and value-added chemicals in a sustainable way.
      Unfortunately, the current state of genome engineering tools for cyanobacteria
      lags far behind those of model organisms such as Escherichia coli and
      Saccharomyces cerevisiae. In this review, we present the current state of
      synthetic biology tools for genome engineering efforts in the most widely used
      cyanobacteria strains and areas that need concerted research efforts to improve
      tool development. Cyanobacteria pose unique challenges to genome engineering
      efforts because their cellular biology differs significantly from other
      eubacteria; therefore, tools developed for other genera are not directly
      transferrable. Standardized parts, such as promoters and ribosome binding sites,
      which control gene expression, require characterization in cyanobacteria in order
      to have fully predictable results. The application of these tools to genome
      engineering efforts is also discussed; the ability to do genome-wide searching
      and to introduce multiple mutations simultaneously is an area that needs
      additional research in order to enable fast and efficient strain engineering. 

PMID- 25985323
TI  - DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1
      in Tumorigenesis.
AB  - DAX1 transcription factor is a key determinant of adrenogonadal development,
      acting as a repressor of SF1 targets in steroidogenesis. It was recently
      demonstrated that DAX1 regulates pluripotency and differentiation in murine
      embryonic stem cells. In this study, we investigated DAX1 expression in
      adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical
      parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34
      children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30
      carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real
      time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34)
      and 24% (17 out of 70) of pediatric and adult ACTs, respectively (chi(2)=10.1,
      p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were
      diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5
      4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with
      functional status in ACTs. Interestingly, a positive correlation was observed
      between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55
      for each group separately; p<0.0001). In addition, DAX1 gene expression was
      significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In
      conclusion, DAX1 strong protein expression was more frequent in pediatric than in
      adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs,
      suggesting that these transcription factors might cooperate in adrenocortical
      tumorigenesis. 

PMID- 25985321
TI  - Clinical Features of Alzheimer Disease With and Without Lewy Bodies.
AB  - IMPORTANCE: Lewy bodies are a frequent coexisting pathology in late-onset
      Alzheimer disease (AD). Previous studies have examined the contribution of Lewy
      bodies to the clinical phenotype of late-onset AD with variable findings.
      OBJECTIVE: To determine whether the presence of Lewy body pathology influences
      the clinical phenotype and progression of symptoms in longitudinally assessed
      participants with AD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective clinical
      and pathological cohort study of 531 deceased participants who met the
      neuropathologic criteria for intermediate or high likelihood of AD according to
      the National Institute on Aging-Ronald Reagan Institute guidelines for the
      neuropathologic diagnosis of AD. All participants had a clinical assessment
      within 2 years of death. The data were obtained from 34 AD centers maintained by
      the National Alzheimer Coordinating Center and spanned from September 12, 2005,
      to April 30, 2013. EXPOSURES: Standardized neuropathologic assessment and then
      brain autopsy after death. MAIN OUTCOMES AND MEASURES: Clinical and
      neuropsychiatric test scores. RESULTS: The mean (SD) age at death was
      statistically significantly younger for participants who had AD with Lewy bodies
      (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2
      [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also
      younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for
      participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More
      men than women had AD with Lewy bodies (P = .01). The frequency of having at
      least 1 APOE epsilon4 allele was higher for participants who had AD with Lewy
      bodies than for participants who had AD without Lewy bodies (P = .03). After
      adjusting for age, sex, education, frequency of plaques (neuritic and diffuse),
      and tangle stage, we found that participants who had AD with Lewy bodies had a
      statistically significantly higher mean (SD) Neuropsychiatric Inventory
      Questionnaire score (6.59 [1.44] [95% CI, 3.75-9.42] vs 5.49 [1.39] [95% CI, 2.76
      8.23]; P = .04) and a statistically significantly higher mean (SD) Unified
      Parkinson Disease Rating Scale motor score (0.81 [0.18] [95% CI, 0.45-1.17] vs
      0.54 [0.18] [95% CI, 0.19-0.88]; P < .001) than did participants who had AD
      without Lewy bodies. CONCLUSIONS AND RELEVANCE: Participants with both AD and
      Lewy body pathology have a clinical phenotype that may be distinguished from AD
      alone. The frequency of Lewy bodies in AD and the association of Lewy bodies with
      the APOE epsilon4 allele suggest potential common mechanisms for AD and Lewy body
      pathologies.

PMID- 25985324
TI  - The effect of low calorie diet on adiponectin concentration: a systematic review
      and meta-analysis.
AB  - Adiponectin secreted from adipose tissue is proposed to be inversely related to
      the body fat mass. However, the magnitude of the effect of low calorie diet on
      adiponectin concentrations remains unknown. The present study was aimed to
      conduct a systematic review and meta-analysis on clinical trials that access the
      effect of low calorie diet on adiponectin concentration. We searched PubMed,
      SCOPUS, ISI web of science, and Google scholar for RCTs until January 2015.
      Totally, 13 trials were found, which examined the effect of low calorie diet on
      adiponectin concentration compared control group without low calorie diet.Our
      meta-analysis showed that weight loss diet can substantially increase the
      adiponectin concentration in overall (Hedges' g=0.34, 95% CI:0.17-0.50, p<0.001).
      Subgroup analysis also revealed that the low calorie diet can substantially
      enhance adiponectin concentrations when prescribed for <=16 weeks (Hedges'
      g=0.48, 95% CI: 0.12-0.83, p=0.01) compared to >16 weeks (Hedges' g=0.30, 95% CI:
      0.11-0.48, p=0.002). Weight loss diet beneficially affects blood adiponectin
      concentrations. More clinical trials are recommended to clear this effect among
      different genders and nationalities, and assess the magnitude of the effect based
      on changes in fat mass. 

PMID- 25985326
TI  - Aging effects in item and associative recognition memory for pictures and words.
AB  - Item and associative recognition for pictures and words with college-age young
      adults and 60-75-year-old adults were examined in the experiment reported in this
      article. The diffusion model (Ratcliff & McKoon, 2008) was used to extract
      estimates of components of processing from the empirical values of accuracy and
      correct and error response time distributions. The model fit the empirical data
      well for both picture and word stimuli. Results showed that boundary separation
      was larger and nondecision time was longer for older relative to young adults.
      Drift rates were not lower for older adults for item recognition but they were
      for associative recognition, indicating that the richer structure of pictures did
      not provide an enhanced ability to form associations for the older adults. There
      were also significant correlations among the components of processing across the
      tasks of the experiment, suggesting common factors, but participants' accuracy
      and response times did not significantly correlate within and across the tasks.

PMID- 25985325
TI  - Elevated homocysteine level and folate deficiency associated with increased
      overall risk of carcinogenesis: meta-analysis of 83 case-control studies
      involving 35,758 individuals.
AB  - BACKGROUND: Results of the association of folate metabolism and carcinogenesis
      are conflicting. We performed a meta-analysis to examine the effect of the
      interaction of serum concentration of homocysteine (Hcy), folate, and vitamin B12
      and 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism on risk of
      cancer overall. METHOD: Two reviewers independently searched for all published
      studies of Hcy and cancer in PubMed, EMBASE-MEDLINE and Chinese databases. Pooled
      results were reported as odds ratios (ORs) and mean differences and presented
      with 95% confidence intervals (95% CIs) and 2-sided probability values. RESULTS:
      We identified 83 eligible studies of 15,046 cases and 20,712 controls. High level
      of Hcy but low level of folate was associated with risk of cancer overall, with
      little effect by type of cancer or ethnicity. Vitamin B12 level was inversely
      associated with only urinary-system and gastrointestinal carcinomas and for Asian
      and Middle Eastern patients. As well, MTHFR C677T, A1298C and G1793A
      polymorphisms were related to elevated serum level of Hcy, and folate and vitamin
      B12 deficiency. However, only MTHFR C677T homogeneity/wild-type (TT/CC)
      polymorphism was positively associated with overall risk of cancer. CONCLUSION:
      Elevated serum Hcy level and folate deficiency are associated with increased
      overall risk of cancer.

PMID- 25985327
TI  - RAS inhibitors' dose-dependent efficacy: myth or reality?
AB  - OBJECTIVE: Treatment of hypertension remains challenging in clinical practice.
      One major problem is incorrect utilization of the principal drug classes. Drugs
      from each class are currently used in accordance with an assumption that the
      blood pressure (BP) lowering effect is dose dependent. While this is true for
      most drugs, it is not appropriate for all drugs that block the renin-angiotensin
      system (RAS). METHODS: This review is based on a PubMed/Cochrane database search
      for articles on the dose-dependent effect of RAS blockers on BP and
      cardiovascular protection. RESULTS: Of the RAS blockers, most angiotensin
      converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have
      a flat dose-response curve for BP decrease, meaning an increase in dose prolongs
      duration of action, but does not yield greater potency. Perindopril is the only
      ACE inhibitor to show a real dose-response curve for BP decrease. While the
      effectiveness of RAS blockers on target organ damage is dose dependent and at
      least partially unrelated to BP control, there is evidence that the only way to
      obtain a beneficial effect is to use them at full dose. Thus, RAS blockers need
      to be used at the correct dose, based on the results of controlled clinical
      trials and meta-analysis. Furthermore, for all-cause mortality, ACE inhibitors
      have been shown to be better than ARBs, a specific efficacy supported by
      perindopril-based studies including ASCOT-BPLA (the Anglo-Scandinavian Cardiac
      Outcomes Trial-BP Lowering Arm), ADVANCE (the Action in Diabetes and Vascular
      disease: PreterAx and DiamicroN-MR Controlled Evaluation trial) and HYVET
      (HYpertension in the Very Elderly Trial). CONCLUSION: In hypertensive patients, a
      strategy based on ACE inhibitors with dose-dependent efficacy such as perindopril
      as optimal treatment should lead both to improved BP control and to a better
      protection from target organ damage, thereby reducing the incidence of
      cardiovascular events.

PMID- 25985329
TI  - Who should be vaccinated against HPV?

PMID- 25985330
TI  - A puzzling airway problem.

PMID- 25985328
TI  - Direct benefit of vaccinating boys along with girls against oncogenic human
      papillomavirus: bayesian evidence synthesis.
AB  - OBJECTIVE: To assess the reduction in the vaccine preventable burden of cancer in
      men if boys are vaccinated along with girls against oncogenic human
      papillomavirus (HPV). DESIGN: Bayesian evidence synthesis approach used to
      evaluate the impact of vaccination against HPV types 16 and 18 on the burden of
      anal, penile, and oropharyngeal carcinomas among heterosexual men and men who
      have sex with men. The reduced transmission of vaccine-type HPV from vaccination
      of girls was assumed to lower the risk of HPV associated cancer in all men but
      not to affect the excess risk of HPV associated cancers among men who have sex
      with men. SETTING: General population in the Netherlands. INTERVENTION: Inclusion
      of boys aged 12 into HPV vaccination programmes. MAIN OUTCOME MEASURES: Quality
      adjusted life years (QALYs) and numbers needed to vaccinate. RESULTS: Before HPV
      vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men
      were lost to vaccine preventable cancers associated with HPV in the Netherlands.
      This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among
      girls remains at the current level of 60%. To prevent one additional case of
      cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour
      specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and
      1975, respectively. The burden of HPV related cancer in men would be reduced by
      66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case,
      1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional
      case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of
      2593, 29107, and 6484, respectively. CONCLUSIONS: Men will benefit indirectly
      from vaccination of girls but remain at risk of cancers associated with HPV. The
      incremental benefit of vaccinating boys when vaccine uptake among girls is high
      is driven by the prevention of anal carcinomas, which underscores the relevance
      of HPV prevention efforts for men who have sex with men.

PMID- 25985331
TI  - Choosing Wisely in the UK: the Academy of Medical Royal Colleges' initiative to
      reduce the harms of too much medicine.

PMID- 25985332
TI  - Politics, medical journals, the medical profession and the Israel lobby.

PMID- 25985334
TI  - Survey reveals poor public awareness of miscarriage.

PMID- 25985335
TI  - Dangers of rising indemnity insurance costs.

PMID- 25985333
TI  - Does long term use of psychiatric drugs cause more harm than good?

PMID- 25985336
TI  - India records large rise in malaria cases in 2014.

PMID- 25985337
TI  - Tax processed food to subsidise healthier options and tackle obesity, says think
      tank.

PMID- 25985338
TI  - Study links changes to primary care in England to rise in hospital admissions of
      children.

PMID- 25985339
TI  - New England Journal of Medicine reconsiders relationship with industry.

PMID- 25985340
TI  - Tackle shortfall in NHS funding, healthcare leaders tell health secretary.

PMID- 25985341
TI  - Lawsuit challenges FDA's authority to prevent off-label marketing.

PMID- 25985342
TI  - Field hospital in Kathmandu treated 1500 patients in two weeks.

PMID- 25985343
TI  - Cheek swab can detect early signs of cancer, study indicates.

PMID- 25985344
TI  - Philippines records highest number of new HIV cases since 1984.

PMID- 25985345
TI  - Migrants' access to healthcare is restricted across Europe, charity warns.

PMID- 25985346
TI  - Gentle daily exercise is as good for elderly men as stopping smoking.

PMID- 25985347
TI  - Remote districts are still inaccessible five days after second Nepal earthquake.

PMID- 25985348
TI  - Prevalence of HPV is high among Indian tribal girls and young women, study finds.

PMID- 25985349
TI  - Enhanced Carrier Collection from CdS Passivated Grains in Solution-Processed
      Cu2ZnSn(S,Se)4 Solar Cells.
AB  - Solution processing of Cu2ZnSn(S,Se)4 (CZTSSe)-kesterite solar cells is
      attractive because of easy manufacturing using readily available metal salts. The
      solution-processed CZTSSe absorbers, however, often suffer from poor morphology
      with a bilayer structure, exhibiting a dense top crust and a porous bottom layer,
      albeit yielding efficiencies of over 10%. To understand whether the cell
      performance is limited by this porous layer, a systematic compositional study
      using (scanning) transmission electron microscopy ((S)TEM) and energy-dispersive
      X-ray spectroscopy of the dimethyl sulfoxide processed CZTSSe absorbers is
      presented. TEM investigation revealed a thin layer of CdS that is formed around
      the small CZTSSe grains in the porous bottom layer during the chemical bath
      deposition step. This CdS passivation is found to be beneficial for the cell
      performance as it increases the carrier collection and facilitates the electron
      transport. Electron-beam-induced current measurements reveal an enhanced carrier
      collection for this buried region as compared to reference cells with evaporated
      CdS. 

PMID- 25985350
TI  - News From the International Council on Women's Health Issues.

PMID- 25985351
TI  - On-Resin Conjugation of Diene-Polyamides and Maleimides via Diels-Alder
      Cycloaddition.
AB  - The reaction between maleimides and resin-linked diene-polyamides allows the
      latter to be used in the preparation of conjugates. Conjugation takes place by
      reacting the insoluble, hydrophobic diene component either with water-soluble
      dienophiles or with dienophiles requiring mixtures of water and organic solvents.
      Experimental conditions can be adjusted to furnish the target conjugate in good
      yield with no need of adding large excesses of soluble reagent. In case protected
      maleimides are used, maleimide deprotection and Diels-Alder cycloaddition can be
      simultaneously carried out to render conjugates with different linking positions.
      On-resin conjugation is followed by an acidic treatment that removes the
      polyamide protecting groups with no harm to the cycloadduct, in contrast with the
      unreacted diene that is indeed degraded under these conditions. Cycloadducts
      incorporating suitable functional groups can undergo subsequent additional
      conjugation reactions in solution to furnish double conjugates. 

PMID- 25985352
TI  - Correlating wine quality indicators to chemical and sensory measurements.
AB  - Twenty-seven commercial Californian Cabernet Sauvignon wines of different quality
      categories were analyzed with sensory and chemical methods. Correlations between
      five quality proxies-points awarded during a wine competition, wine expert
      scores, retail price, vintage, and wine region-were correlated to sensory
      attributes, volatile compounds, and elemental composition. Wine quality is a
      multi-faceted construct, incorporating many different layers. Depending on the
      quality proxy studied, significant correlations between quality and attributes,
      volatiles and elements were found, some of them previously reported in the
      literature. 

PMID- 25985353
TI  - Isoindolinones as Michael Donors under Phase Transfer Catalysis: Enantioselective
      Synthesis of Phthalimidines Containing a Tetrasubstituted Carbon Stereocenter.
AB  - Readily available chiral ammonium salts derived from cinchona alkaloids have
      proven to be effective phase transfer catalysts in the asymmetric Michael
      reaction of 3-substituted isoindolinones. This protocol provides a convenient
      method for the construction of valuable asymmetric 3,3-disubstituted
      isoindolinones in high yields and  moderate to good enantioselectivity.
      Diastereoselectivity was also investigated in the construction of contiguous
      tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor
      led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via
      a tandem conjugated addition/cyclization reaction. 

PMID- 25985354
TI  - Microwave-Assisted Synthesis of Novel Pyrazolo[3,4-g][1,8]naphthyridin-5-amine
      with Potential Antifungal and Antitumor Activity.
AB  - The microwave assisted reaction between heterocyclic o-aminonitriles 1 and cyclic
      ketones 2 catalyzed by zinc chloride led to new series of pyrazolo[3,4-b]
      [1,8]naphthyridin-5-amines 3 in good yields. This procedure provides several
      advantages such as being environmentally friendly, high yields, simple work-up
      procedure, broad scope of applicability and the protocol provides an alternative
      for the synthesis of pyrazolonaphthyridines. The whole series showed antifungal
      activities against Candida albicans and Cryptococcus neoformans standardized
      strains, being compounds with a 4-p-tolyl substituent of the naphthyridin
      scheleton (3a, 3d and 3g), the most active ones mainly against C. albicans, which
      appear to be related to their comparative hydrophobicity. Among them, 3d,
      containing a cyclohexyl fused ring, showed the best activity. The anti-Candida
      activity was corroborated by testing the three most active compounds against
      clinical isolates of albicans and non-albicans Candida strains. These compounds
      were also screened by the US National Cancer Institute (NCI) for their ability to
      inhibit 60 different human tumor cell lines. Compounds 3a and 3e showed
      remarkable antitumor activity against cancer cell lines, with the most important
      GI50 values ranging from 0.62 to 2.18 MUM. 

PMID- 25985355
TI  - A Comprehensive Review on the Phytochemical Constituents and Pharmacological
      Activities of Pogostemon cablin Benth.: An Aromatic Medicinal Plant of Industrial
      Importance.
AB  - Pogostemon cablin Benth. (patchouli) is an important herb which possesses many
      therapeutic properties and is widely used in the fragrance industries. In
      traditional medicinal practices, it is used to treat colds, headaches, fever,
      nausea, vomiting, diarrhea, abdominal pain, insect and snake bites. In
      aromatherapy, patchouli oil is used to relieve depression, stress, calm nerves,
      control appetite and to improve sexual interest. Till now more than 140
      compounds, including terpenoids, phytosterols, flavonoids, organic acids,
      lignins, alkaloids, glycosides, alcohols, aldehydes have been isolated and
      identified from patchouli. The main phytochemical compounds are patchouli
      alcohol, alpha-patchoulene, beta-patchoulene, alpha-bulnesene, seychellene,
      norpatchoulenol, pogostone, eugenol and pogostol. Modern studies have revealed
      several biological activities such as antioxidant, analgesic, anti-inflammatory,
      antiplatelet, antithrombotic, aphrodisiac, antidepressant, antimutagenic,
      antiemetic, fibrinolytic and cytotoxic activities. However, some of the
      traditional uses need to be verified and may require standardizing and
      authenticating the bioactivity of purified compounds through scientific methods.
      The aim of the present review is to provide comprehensive knowledge on the
      phytochemistry and pharmacological activities of essential oil and different
      plant extracts of patchouli based on the available scientific literature. This
      information will provide a potential guide in exploring the use of main active
      compounds of patchouli in various medical fields. 

PMID- 25985356
TI  - High Fluorescent Porphyrin-PAMAM-Fluorene Dendrimers.
AB  - Two new classes of dendrimers bearing 8 and 32 fluorene donor groups have been
      synthesized. The first and second generations of these porphyrin-PAMAM-fluorene
      dendrimers were characterized by 1H-NMR, 13C-NMR, FTIR, UV-vis spectroscopy,
      elemental analyses and MALDI-TOF mass spectrometry. The UV-vis spectra showed
      that the individual properties of donor and acceptor moieties were preserved,
      indicating that the new dendrimers could be used as photosynthetic antennae.
      Furthermore, for fluorescent spectroscopy, these dendrimers showed good energy
      transfer. 

PMID- 25985357
TI  - Recovery of steroidal alkaloids from potato peels using pressurized liquid
      extraction.
AB  - A higher yield of glycoalkaloids was recovered from potato peels using
      pressurized liquid extraction (1.92 mg/g dried potato peels) compared to
      conventional solid-liquid extraction (0.981 mg/g dried potato peels). Response
      surface methodology deduced the optimal temperature and extracting solvent
      (methanol) for the pressurized liquid extraction (PLE) of glycoalkaloids as 80 
      degrees C in 89% methanol. Using these two optimum PLE conditions, levels of
      individual steroidal alkaloids obtained were of 597, 873, 374 and 75 ug/g dried
      potato peel for alpha-solanine, alpha-chaconine, solanidine and demissidine
      respectively. Corresponding values for solid liquid extraction were 59%, 46%, 40%
      and 52% lower for alpha-solanine, alpha-chaconine, solanidine and demissidine
      respectively. 

PMID- 25985358
TI  - Highly diastereoselective synthesis of spiropyrazolones.
AB  - We report a highly diastereoselective synthesis of spiropyrazolones catalyzed by
      secondary amines. The reported Michael-Aldol cascade reaction affords the desired
      spiropyrazolones bearing four chiral centers as a single diastereomer in
      excellent yields. 

PMID- 25985359
TI  - Studies on transition metal-quercetin complexes using electrospray ionization
      tandem mass spectrometry.
AB  - To systematically study the effects of the number of d electrons of the first
      transition metal ions (Fe, Co, Ni, Cu and Zn) on the formation and stability of
      metal flavonoid complexes, we took the quercetin/M2+ complex as a model system to
      investigate the structures and properties of these complexes. Based on
      considerable structural information obtained through ESI-MSn, all of the first
      transition metal ions (Fe2+, Co2+, Ni2+, Cu2+ and Zn2+) were found to form
      different complexes with quercetin, while with the number of chelating flavonoids
      decreasing along with the reduction of the metal ionic radius. Quercetin forms
      different complexes with the above metal divalent ions through its 5-OH and 4
      carbonyl groups; the complex stability is highly dependent on both the metallic
      ion and the flavonoid chelator itself. As for the central ion (M2+), when
      chelated with quercetin to form the complex, the stability of the complex
      decreased in the following order: Cu2+ > Ni2+ > Co2+ > Fe2+ > Zn2+. With
      flavonoid: metal stoichiometries at 2:1, the complexes formed between quercetin
      and metal ions (Fe2+, Ni2+, Co2+ and Zn2+) have the similar fragmentation
      mechanism, while Cu2+ displayed different fragmentation mechanism due to the
      concurrent oxidation. 

PMID- 25985360
TI  - Biological activity and photostability of biflorin micellar nanostructures.
AB  - Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in
      its roots a compound named biflorin, an o-naphthoquinone that shows activity
      against Gram-positive bacteria and fungi and also presents antitumor and
      antimetastatic activities. However, biflorin is hydrophobic and photosensitive.
      These properties make its application difficult. In this work we prepared
      biflorin micellar nanostructures looking for a more effective vehiculation and
      better preservation of the biological activity. Biflorin was obtained, purified
      and characterized by UV-Vis, infrared (IR) and 1H- and 13C-NMR. Micellar
      nanostructures of biflorin were then assembled with Tween 80(r), Tween 20(r) and
      saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light
      scattering (DLS). The results showed that the micellar nanostructures were stable
      and presented an average size of 8.3 nm. Biflorin micellar nanostructures'
      photodegradation was evaluated in comparison with biflorin in ethanol. Results
      showed that the biflorin in micellar nanostructures was better protected from
      light than biflorin dissolved in ethanol, and also indicated that biflorin in
      micelles were efficient against Gram-positive bacteria and yeast species. In
      conclusion, the results showed that the micellar nanostructures could ensure the
      maintenance of the biological activity of biflorin, conferring photoprotection.
      Moreover, biflorin vehiculation in aqueous media was improved, favoring its
      applicability in biological systems. 

PMID- 25985361
TI  - Mentha suaveolens Ehrh. (Lamiaceae) Essential Oil and Its Main Constituent
      Piperitenone Oxide: Biological Activities and Chemistry.
AB  - Since herbal medicines play an important role in the treatment of a wide range of
      diseases, there is a growing need for their quality control and standardization.
      Mentha suaveolens Ehrh. (MS) is an aromatic herb with fruit and a spearmint
      flavor, used in the Mediterranean areas as a traditional medicine. It has an
      extensive range of biological activities, including cytotoxic, antimicrobial,
      antioxidant, anti-inflammatory, hypotensive and insecticidal properties, among
      others. This study aims to review the scientific findings and research reported
      to date on MS that prove many of the remarkable various biological actions,
      effects and some uses of this species as a source of bioactive natural compounds.
      On the other hand, piperitenone oxide (PO), the major chemical constituent of the
      carvone pathway MS essential oil, has been reported to exhibit numerous
      bioactivities in cells and animals. Thus, this integrated overview also surveys
      and interprets the present knowledge of chemistry and analysis of this oxygenated
      monoterpene, as well as its beneficial bioactivities. Areas for future research
      are suggested. 

PMID- 25985362
TI  - Synthesis, biological activities, and quantitative structure-activity
      relationship (QSAR) study of novel camptothecin analogues.
AB  - In continuation of our program aimed at the development of natural product-based
      pesticidal agents, three series of novel camptothecin derivatives were designed,
      synthesized, and evaluated for their biological activities against T.
      Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good
      to-excellent activity against three insect species tested, with LC50 values
      ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were
      more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed
      superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared
      with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed
      bioactivities, preliminary structure-activity relationship (SAR) correlations
      were also discussed. Furthermore, a three-dimensional quantitative structure
      activity relationship (3D-QSAR) model using comparative molecular field analysis
      (CoMFA) was built. The model gave statistically significant results with the
      cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and 
      of 0.993. The QSAR analysis indicated that the size of the substituents play an
      important in the activity of 7-modified camptothecin derivatives. These findings
      will pave the way for further design, structural optimization, and development of
      camptothecin-derived compounds as pesticidal agents. 

PMID- 25985363
TI  - Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in
      breast cancer.
AB  - Neurofilament heavy polypeptide (NEFH) has recently been identified as a
      candidate DNA hypermethylated gene within the functional breast cancer
      hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide
      (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which
      are structural components of the cytoskeleton in mature neurons. Recent studies
      reported the deregulation of these proteins in several malignancies, suggesting
      that neurofilaments may have a role in other cell types as well. Using a
      comprehensive approach, we studied the epigenetic inactivation of neurofilament
      genes in breast cancer and the functional significance of this event. We report
      that DNA methylation-associated silencing of NEFH, NEFL, and NEFM in breast
      cancer is frequent, cancer-specific, and correlates with clinical features of
      disease progression. DNA methylation-mediated inactivation of these genes occurs
      also in multiple other cancer histologies including pancreas, gastric, and colon.
      Restoration of NEFH function, the major subunit of the neurofilament complex,
      reduces proliferation and growth of breast cancer cells and arrests them in Go/G1
      phase of the cell cycle along with a reduction in migration and invasion. These
      findings suggest that DNA methylation-mediated silencing of the neurofilament
      genes NEFH, NEFM, and NEFL are frequent events that may contribute to the
      progression of breast cancer and possibly other malignancies.

PMID- 25985364
TI  - KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in
      atherosclerotic plaque pathogenesis.
AB  - Previous studies investigating the role of smooth muscle cells (SMCs) and
      macrophages in the pathogenesis of atherosclerosis have provided controversial
      results owing to the use of unreliable methods for clearly identifying each of
      these cell types. Here, using Myh11-CreER(T2) ROSA floxed STOP eYFP Apoe(-/-)
      mice to perform SMC lineage tracing, we find that traditional methods for
      detecting SMCs based on immunostaining for SMC markers fail to detect >80% of SMC
      derived cells within advanced atherosclerotic lesions. These unidentified SMC
      derived cells exhibit phenotypes of other cell lineages, including macrophages
      and mesenchymal stem cells (MSCs). SMC-specific conditional knockout of Kruppel
      like factor 4 (Klf4) resulted in reduced numbers of SMC-derived MSC- and
      macrophage-like cells, a marked reduction in lesion size, and increases in
      multiple indices of plaque stability, including an increase in fibrous cap
      thickness as compared to wild-type controls. On the basis of in vivo KLF4
      chromatin immunoprecipitation-sequencing (ChIP-seq) analyses and studies of
      cholesterol-treated cultured SMCs, we identified >800 KLF4 target genes,
      including many that regulate pro-inflammatory responses of SMCs. Our findings
      indicate that the contribution of SMCs to atherosclerotic plaques has been
      greatly underestimated, and that KLF4-dependent transitions in SMC phenotype are
      critical in lesion pathogenesis. 

PMID- 25985366
TI  - Sonication-Assisted Layer-by-Layer Assembly for Low Solubility Drug
      Nanoformulation.
AB  - Sonication-assisted layer-by-layer (LbL) self-assembly is a nanoencapsulation
      technique based on the alternate adsorption of oppositely charged
      polyelectrolytes, enabling the encapsulation of low solubility drugs. In this
      work, a top-down LbL technique was performed using a washless approach and
      ibuprofen (IBF) as a model class II drug. For each saturated layer deposition,
      polyelectrolyte concentration was determined by titration curves. The first layer
      was constituted by cationic poly(allylamine hydrochloride) (PAH), given the IBF
      negative surface charge, followed by anionic polystyrenesulfonate (PSS). This
      polyelectrolyte sequence was made up with 2.5, 5.5, and 7.5 bilayer nanoshells.
      IBF nanoparticles (NPs) coated with 7.5 bilayers of PAH/PSS showed 127.5 +/- 38.0
      nm of particle size, a PDI of 0.24, and a high zeta potential (+32.7 +/- 0.6 mV),
      allowing for a stable aqueous nanocolloid of the drug. IBF entrapment efficiency
      of 72.1 +/- 5.8% was determined by HPLC quantification. In vitro MTT assay showed
      that LbL NPs were biocompatible. According to the number of coating layers, a
      controlled release of IBF from LbL NPs was achieved under simulated intestinal
      conditions (from 5 h up to 7 days). PAH/PSS-LbL NPs constitute a potential
      delivery system to improve biopharmaceutical parameters of water low solubility
      drugs. 

PMID- 25985365
TI  - The microRNA-200 family regulates pancreatic beta cell survival in type 2
      diabetes.
AB  - Pancreatic beta cell death is a hallmark of type 1 (T1D) and type 2 (T2D)
      diabetes, but the molecular mechanisms underlying this aspect of diabetic
      pathology are poorly understood. Here we report that expression of the microRNA
      (miR)-200 family is strongly induced in islets of diabetic mice and that beta
      cell-specific overexpression of miR-200 in mice is sufficient to induce beta cell
      apoptosis and lethal T2D. Conversely, mir-200 ablation in mice reduces beta cell
      apoptosis and ameliorates T2D. We show that miR-200 negatively regulates a
      conserved anti-apoptotic and stress-resistance network that includes the
      essential beta cell chaperone Dnajc3 (also known as p58IPK) and the caspase
      inhibitor Xiap. We also observed that mir-200 dosage positively controls
      activation of the tumor suppressor Trp53 and thereby creates a pro-apoptotic gene
      expression signature found in islets of diabetic mice. Consequently, miR-200
      induced T2D is suppressed by interfering with the signaling of Trp53 and Bax, a
      proapoptotic member of the B cell lymphoma 2 protein family. Our results reveal a
      crucial role for the miR-200 family in beta cell survival and the pathophysiology
      of diabetes. 

PMID- 25985367
TI  - Percutaneous Doxycycline Treatment of Juxtaphyseal Aneurysmal Bone Cysts.
AB  - BACKGROUND: A recurrence rate of 19% to 23% has been reported in juxtaphyseal
      aneurysmal bone cysts (ABC) without en bloc resection or amputation. No
      percutaneous surgical techniques or drug treatments have demonstrated consistent
      bone healing with normal physeal growth and a recurrence rate of <19%.
      Doxycycline has properties that may make it an appropriate agent for percutaneous
      treatment of juxtaphyseal ABC in skeletally immature patients. METHODS: We
      retrospectively reviewed 16 patients who underwent percutaneous treatment of ABCs
      with doxycycline from 2006 to 2011. The mean age was 7.1 years (range, 2 to 15
      y). There were 16 treatment locations: humerus (9), tibia (3), fibula (2), femur
      (1), and ulna (1). Sixteen patients completed treatment involving 102 treatment
      sessions (2 to 14 sessions per patient). Treatment response was evaluated
      radiographically by measuring the lytic component, thickness of involved cortex,
      and signs of bony remodeling, and evidence of physeal growth arrest. Recurrence
      was indicated by new areas of lytic destruction after completion of treatment.
      The minimum follow-up was 18 months (mean, 39 mo). RESULTS: All 16 patients
      demonstrated reduction in lytic destruction, bony healing, and bony remodeling.
      One patient demonstrated recurrent minimal lytic destruction after 20 months of
      observation. Seven patients (7/16, 44%) demonstrated physeal ABC involvement; 5
      of 7 patients healed with a physeal bone bridge, all <=15% of the physeal surface
      area, 1 with mild central physeal deformity. All patients with focal transphyseal
      ABC involvement (4/4, 100%) demonstrated focal bone bridge after treatment. No
      patient had diffuse physeal growth arrest; only patients with intraphyseal or
      transphyseal ABC involvement had focal physeal growth arrest. CONCLUSIONS: In
      this series, patients undergoing percutaneous doxycycline treatment of
      juxtaphyseal ABCs demonstrated ABC healing and a recurrence rate of 6% at >18
      months. Patients without physeal ABC involvement demonstrated no evidence of
      physeal growth arrest.

PMID- 25985368
TI  - Trends in Pediatric and Adolescent Anterior Cruciate Ligament Injury and
      Reconstruction.
AB  - BACKGROUND: With the increasing involvement in organized athletics among children
      and adolescents, more anterior cruciate ligament (ACL) injuries are being
      recognized in the skeletally immature population. The goal of the present study
      is to utilize a national database to characterize the recent epidemiologic trends
      of ACL injuries, ACL reconstruction, and treatment of associated meniscal and
      chondral pathology in the pediatric and adolescent populations. METHODS: A
      national database was queried for ACL tear (ICD-9 844.2) and arthroscopic
      reconstruction of an ACL tear (CPT 29888) from 2007 to 2011. Searches were
      limited by age group to identify pediatric and adolescent cohorts: (1) ages 5 to
      9 years old, (2) ages 10 to 14 years old, and (3) ages 15 to 19 years old. A
      comparative cohort of adult patients from ages 20 to 45 was also created. The
      database was also queried for concomitant procedures at the same time as ACL
      reconstruction for each age group, including partial meniscectomy, meniscus
      repair, microfracture, osteochondral autograft or allograft transfer, and shaving
      chondroplasty. The chi analysis was used to determine statistical significance.
      RESULTS: A total of 44,815 unique pediatric or adolescent patients with a
      diagnosis of an ACL tear and 19,053 pediatric or adolescent patients who
      underwent arthroscopic ACL reconstruction were identified. Significant increases
      in pediatric and adolescent ACL tear diagnosis and reconstruction compared with
      adult patients were noted. Significant increases in many concomitant meniscus and
      cartilage procedures in pediatric and adolescent patients compared with adult
      patients were also noted. CONCLUSIONS: The present study demonstrates a
      significant increase in the overall diagnosis of ACL injury and ACL
      reconstruction in both pediatric and adolescent patients, rising at a rate
      significantly higher than adults. In addition, pediatric and adolescent patients
      who undergo ACL reconstruction had significant increases in incidences of
      concomitant meniscal and cartilage procedures. LEVEL OF EVIDENCE: Level III
      retrospective cohort study.

PMID- 25985369
TI  - Treatment of Calcaneal Apophysitis: Wait and See Versus Orthotic Device Versus
      Physical Therapy: A Pragmatic Therapeutic Randomized Clinical Trial.
AB  - BACKGROUND: Calcaneal apophysitis is a frequent cause of heel pain in children
      and is known to have a significant negative effect on the quality of life in
      affected children. The most effective treatment is currently unknown. The purpose
      of this study is to evaluate 3 frequently used conventional treatment modalities
      for calcaneal apophysitis. METHODS: Three treatment modalities were evaluated and
      compared in a prospective randomized single-blind setting: a pragmatic wait and
      see protocol versus a heel raise inlay (ViscoHeel; Bauerfeind) versus an
      eccentric exercise regime under physiotherapeutic supervision. Treatment duration
      was 10 weeks. INCLUSION CRITERIA: age between 8 and 15 years old, at least 4
      weeks of heel pain complaints due to calcaneal apophysitis based, with a minimal
      Faces Pain Scale-Revised of 3 points. Primary exclusion criteria included other
      causes of heel pain and previous similar treatment. Primary outcome was Faces
      Pain Scale-Revised at 3 months. Secondary outcomes included patient satisfaction
      and Oxford Ankle and Foot Questionnaire (OAFQ). Points of measure were at
      baseline, 6 weeks, and 3 months. Analysis was performed according to the
      intention-to-treat principles. RESULTS: A total of 101 subjects were included.
      Three subjects were lost to follow-up. At 6 weeks, the heel raise subjects were
      more satisfied compared with both other groups (P<0.01); the heel raise group
      improved significantly compared with the wait and see group for OAFQ Children
      (P<0.01); the physical therapy group showed significant improvement compared with
      the wait and see group for OAFQ Parents (P<0.01). Each treatment modality showed
      significant improvement of all outcome measures during follow-up (P<0.005). No
      clinical relevant differences were found between the respective treatment
      modalities at final follow-up. CONCLUSIONS: Treatment with wait and see, a heel
      raise inlay, or physical therapy each resulted in a clinical relevant and
      statistical significant reduction of heel pain due to calcaneal apophysitis. No
      significant difference in heel pain reduction was found between individual
      treatment regimes. Calcaneal apophysitis is effectively treated by the evaluated
      regimes. Physicians should deliberate with patients and parents regarding the
      preferred treatment.

PMID- 25985370
TI  - The Effectiveness of the Ponseti Method for Treating Clubfoot Associated With
      Amniotic Band Syndrome.
AB  - BACKGROUND: Amniotic band syndrome (ABS) is a congenital disorder with an
      associated incidence of clubfoot deformity in over 50% of patients. Although
      early reports in the literature demonstrated a poor response to casting
      treatments, recent application of the Ponseti technique in ABS patients have been
      more promising. METHODS: A retrospective review of all patients with clubfoot and
      a concurrent diagnosis of ABS were reviewed at a single institution. Patients not
      managed initially with the Ponseti method were excluded. Data collected included
      patient age at presentation, sex, unilateral or bilateral, amniotic band location
      and associated findings, and response to treatment-number of casts and
      requirement of Achilles tenotomy, tibialis anterior tendon transfer, or other
      surgical procedures. Duration of treatment at latest follow-up visit was noted
      and outcome was based on clinical foot appearance and plan for any further
      procedures. RESULTS: Twelve patients (7 female and 5 male) with a total of 21
      feet (9 bilateral and 3 unilateral) were identified. The average age at
      presentation was 3 weeks (range, 1 to 9 wk). The average number of casts was 6
      (range, 3 to 11). Seventeen of 21 feet (81.0%) underwent percutaneous Achilles
      tenotomy. The initial correction rate for all patients with the Ponseti technique
      was 20/21 feet (95.2%) and recurrence was noted in 7/21 feet (33.3%). One patient
      underwent primary posteromedial release and 2 patients had associated
      neurological deficits. The average follow-up was 3.9 years (range, 9 mo to 10 y)
      and all but one patient had supple, plantigrade feet. CONCLUSION: The Ponseti
      technique is an effective first-line treatment in patients who have clubfeet
      associated with ABS, including those with a neurological deficit. LEVEL OF
      EVIDENCE: Level IV.

PMID- 25985371
TI  - Calcaneal Scoring as an Adjunct to Modified Oxford Hip Scores: Prediction of
      Contralateral Slipped Capital Femoral Epiphysis.
AB  - BACKGROUND: In 2 recent studies, modified Oxford hip scores of 16 through 18 have
      been shown to predict an extremely high risk of contralateral slipping in
      unilateral slipped capital femoral epiphysis (SCFE). However, the modified Oxford
      system is not widely used. This may be due, in part, to the complexity of the
      scoring system, difficulty in viewing all 5 radiographic features on a single x
      ray and phenotypic variation in the features. Ossification of the calcaneal
      apophysis provides an osteologic marker of skeletal maturation in relation to
      peak height velocity and has been described previously. We examine the value of
      the calcaneal apophyseal ossification sequence for predicting modified Oxford hip
      scores. METHODS: We examined 279 pelvis and matching foot x-rays that were taken
      at the same session from 94 healthy children aged 3 to 18 years. A fellowship
      trained pediatric orthopaedist determined the modified Oxford hip score for each
      hip radiograph. The calcaneal x-rays had been previously graded. Modified Oxford
      hip scores were compared with calcaneal scores for each set of matched hip and
      calcaneal x-rays. RESULTS: Stage 0 to 2 calcanei had 94% of corresponding hip
      radiographs rated as modified Oxford scores of 16 to 18. Stage 3 calcanei had 54%
      rated as 16 to 18 and 31% rated as scores 19 to 21. Stage 4 calcanei had 31%
      rated as scores 19 to 21, and 68% rated as scores 22 to 26. Stage 5 calcanei had
      100% rated as 22 to 26. Using data from Popejoy and colleagues' study, the
      weighted risk of contralateral SCFE was 94% for calcaneal stage 0, 86.5% for
      calcaneal stage 1, 90.3% for calcaneal stage 2, 55.8% for calcaneal stage 3, 6.1%
      for calcaneal stage 4, and 0 for calcaneal stage 5. CONCLUSIONS: Calcaneal stages
      0 to 3 correspond entirely to modified Oxford scores indicating elevated risk of
      contralateral SCFE. The calcaneal scoring system has potential for adjunctive use
      with the modified Oxford score for prediction of contralateral SCFE.

PMID- 25985372
TI  - A Longitudinal Review of Gait Following Treatment for Idiopathic Clubfoot: Gait
      Analysis at 2 and 5 Years of Age.
AB  - BACKGROUND: Initial correction following nonoperative (NonOp) treatment for
      idiopathic clubfoot has been reported in 95% of feet by age 2; however, by age 4,
      approximately one third of feet undergo surgery due to relapse. The purpose of
      this study was to assess the longitudinal effect of growth and surgical (Sx)
      intervention on gait following NonOp and Sx treatment for clubfoot. METHODS:
      Children with idiopathic clubfoot were seen for gait analysis at 2 and 5 years of
      age. Kinematic data were collected at both visits, and kinetic data were
      collected at age 5 years. Group comparisons were made between feet treated with
      the Ponseti casting technique (Ponseti) and the French physical therapy method
      (PT) and between feet treated nonoperatively and surgically. Comparisons were
      made between feet treated with a limited release or tendon transfer (fair) and
      those treated with a full posteromedial release (poor). The alpha was set to 0.05
      for all statistical analyses. RESULTS: Gait data from 181 children with 276
      idiopathic clubfeet were collected at both age 2 and 5 years. Each foot was
      initially treated with either the Ponseti (n=132) or PT (n=144) method but by the
      5-year visit, 30 Ponseti and 61 PT feet required surgery. Gait outcomes showed
      limitations primarily in the Sx clubfeet. Normal ankle motion was only present in
      17% of Ponseti and 21% of PT feet by age 5 following Sx management. Sx PT feet
      showed persistent intoeing at age 2 and 5. Within the Sx group, feet initially
      treated with PT had a clinically significant reduction in ankle power compared
      with those treated initially by the Ponseti method. Feet treated with
      posteromedial releases had significantly less ankle power than those treated with
      limited surgery or that remained NonOp at 5 years. CONCLUSIONS: This longitudinal
      study shows subtle changes between 2 and 5 years, and continues to support a
      NonOp approach in the treatment of clubfoot. LEVEL OF EVIDENCE: Level II
      therapeutic.

PMID- 25985373
TI  - Unicameral Bone Cysts in the Humerus: Treatment Outcomes.
AB  - BACKGROUND: Several treatment modalities have been described for the treatment of
      unicameral bone cysts (UBC). The aim of this study was to examine the outcome of
      various treatment modalities of UBC in a specific anatomic location, the humerus.
      METHODS: This study is a retrospective case-only study of patients with humeral
      UBC with minimum follow-up of 1 year. Medical records and radiographs were
      assessed and UBC healing status was determined based on most recent follow-up
      radiographs and divided into 3 groups (healed, partially healed, and not healed).
      Descriptive statistics were utilized to summarize study outcome. RESULTS: Sixty
      eight patients (54 boys and 14 girls) with humeral UBC comprised the study
      population. Sixty-four cases (94.1%) presented with a pathologic fracture. Fifty
      one cases were in the proximal metaphysis and 17 were in the diaphysis. Mean age
      at diagnosis was 9.2+/-3.7 years, and mean follow-up was 4.0+/-2.6 years. Twenty
      five patients were treated with observation, 38 by injection (27 with steroids
      and 11 with bone marrow), and 5 by open surgery. Patients who underwent open
      surgery had relatively larger cyst length, width, and cyst index, and all healed
      or partially healed at last follow-up. UBC persistence was observed in 29% of
      diaphyseal and 27.5% of metaphyseal cysts. Of the 19 patients with persistence, 8
      were treated with observation, 9 with steroid injection, and 2 with bone marrow
      injection. Inner wall disruption before injection was performed in 17 patients
      (24% did not heal), whereas 21 patients did not have inner wall disruption (33%
      did not heal). Twenty patients received >1 injection. Eleven patients complained
      of pain at the last visit (8 had a persistent cyst, 2 were partially healed, and
      1 had a healed UBC). CONCLUSIONS: Complete healing of humeral UBC is challenging
      to achieve irrespective of treatment modality. UBCs treated with open surgery
      tended to heal better. Unhealed cysts were more likely to be associated with
      pain. LEVEL OF EVIDENCE: Level III-a retrospective comparative study.

PMID- 25985374
TI  - Biomechanical Analysis of Screws Versus K-Wires for Lateral Humeral Condyle
      Fractures.
AB  - BACKGROUND: Good outcomes have been described for pediatric lateral condyle
      fractures treated by open reduction and fixation using either screws or Kirschner
      wires (K-wires). No studies have compared the biomechanical properties of the 2
      fixation methods. We hypothesized that screw fixation would be more
      biomechanically stable than K-wire fixation. METHODS: Synthetic humerus models
      were used for biomechanical testing, following a previously published protocol. A
      miter saw was used to make an oblique cut to simulate a Milch type II fracture.
      Fractures were anatomically reduced and fixed with either 2 divergent 0.062-inch
      K-wires placed bicortically or a 4.0-mm lag screw placed obliquely (perpendicular
      to the fracture line). Specimens were then embedded in polymethyl methacrylate
      bone cement for testing. Mechanical testing using displacement control was
      performed applying compression or distraction from 0 to 1.5 mm at a rate of 0.5
      mm/s for 10 cycles. The maximum force was calculated based on the maximum force
      averaged over the 10 cycles. Stiffness was calculated based on the slope of the
      force-displacement curve of the 10th cycle. A 2-sample t test was used to
      determine significant differences between the stiffness and maximum force
      comparing the K-wire and screw groups. A P-value of <0.05 was considered
      statistically significant. RESULTS: Stiffness and maximum force in tension
      testing were significantly greater with screw fixation compared with K-wire
      fixation. Testing in compression revealed statistically significant increased
      maximum force and a trend towards increased stiffness. CONCLUSION: Screw fixation
      in a synthetic bone model of pediatric lateral condyle fractures (Milch type II)
      provides increased biomechanical stability of the construct as compared with K
      wires. CLINICAL RELEVANCE: If similar effects were seen in vivo, increased
      biomechanical stability with screw fixation could decrease the occurrence of
      complications such as loss of reduction and nonunion.

PMID- 25985375
TI  - Surgical Hip Dislocation for the Treatment of Intra-Articular Injuries and Hip
      Instability Following Traumatic Posterior Dislocation in Children and
      Adolescents.
AB  - BACKGROUND: Traumatic posterior hip dislocation in children is a rare injury that
      typically is treated with closed reduction. Surgical treatment is typically
      recommended for nonconcentric reduction with joint space asymmetry with entrapped
      labrum or an osteochondral fragment. The surgical hip dislocation (SHD) approach
      allows for full assessment of the acetabulum and femoral head and has been our
      preferred surgical strategy. The purpose of this study was to (1) describe the
      intra-articular pathologic findings seen at the time of SHD; and (2) to
      investigate hip pain, function, and activity level of a cohort of children and
      adolescents after open treatment of a posterior hip dislocation using the SHD
      approach. METHODS: Following IRB approval, 23 patients who sustained a traumatic
      posterior hip dislocation between January 2009 and December 2013 were identified.
      In 8/23 (34.8%) patients there was evidence of nonconcentric reduction after
      closed treatment and surgical treatment was performed using the SHD approach.
      Seven male and 1 female (mean age, 11.2 y; range, 6 to 14.6 y) were followed for
      an average of 28 months (range, 13 to 67 mo). The modified Harris Hip Score
      (mHHS) and the University of California Los Angeles activity score assessed
      clinical hip outcome and activity level at minimum of 1 year after surgery.
      RESULTS: Six patients were treated after an acute trauma, whereas 2 were treated
      after recurrent dislocations. Five patients were involved in motor vehicle
      accidents and 3 in sports-related injuries. Intraoperative findings include
      posterior labral avulsion in all patients, fracture of the cartilaginous
      posterior wall (n=3), and femoral head chondral injuries (n=5) and fracture
      (n=1). The labral root was repaired using suture anchor technique in 7/8 patients
      and resected in 1. In 2 patients, labral repair was complemented by screw
      fixation of the posterior wall. All but one patient (mHHS=94) reported maximum
      mHHS. The University of California Los Angeles activity score was 10 for 5/8
      patients and 7 in 3 patients. No case of femoral head osteonecrosis was noted.
      One patient developed an asymptomatic heterotopic ossification. CONCLUSIONS: When
      open reduction is recommended for the treatment of intra-articular pathologies
      and hip instability following traumatic dislocation of the hip in children and
      adolescents, the SHD is an excellent approach that allows surgical correction of
      the damaged bony and soft-tissue structures including repair of the capsule
      labral complex, and reduction and internal fixation of the cartilaginous
      posterior wall and femoral head fractures. LEVEL OF EVIDENCE: Level IV.

PMID- 25985376
TI  - Transactivation of the human retinoid X receptor by organotins: use of site
      directed mutagenesis to identify critical amino acid residues for organotin
      induced transactivation.
AB  - Organotins, such as tributyltin (TBT) and triphenyltin (TPT), may disrupt
      endocrine activity in mammals arising from their ability to act as ligands for
      the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor
      gamma (PPARgamma). The structure of TBT is completely different from that of 9
      cis retinoic acid (9cRA), an endogenous RXR ligand; and X-ray crystallographic
      studies have revealed that TBT and 9cRA have distinct binding interactions with
      human RXRalpha. Therefore, organotins and rexinoids likely activate RXR by
      different mechanisms. Here, we used human RXRalpha mutants to investigate which
      amino acid residues of the receptor are critical for transactivation induced by
      rexinoids and organotins. We found that 9cRA and a synthetic RXR agonist
      (LG100268) failed to activate R316A and L326A RXRalpha mutants. In contrast, all
      the tested organotins activated the R316A mutant, the L326A mutant, or both but
      failed to activate a C432A mutant. These results suggest that the importance of
      L326, which is located in the beta-strand, for rexinoid-induced transactivation
      of RXRalpha is comparable to that of R316; in contrast, C432 is critical for
      organotin-induced transactivation, whereas R316 and L326 are not required. We
      used a PPARgamma/RXRalpha C432A heterodimer to determine whether TBT and TPT
      could activate the heterodimer by binding to PPARgamma. We found that TBT and TPT
      activated the PPARgamma/RXRalpha C432A heterodimer, which suggests that both
      compounds can activate the heterodimer through PPARgamma. These findings indicate
      that the amino acid residues that are critical for organotin-induced
      transactivation of RXRalpha are distinct from those required for rexinoid-induced
      transactivation. 

PMID- 25985378
TI  - Effects of Screw- and Cement-Retained Implant-Supported Prostheses on Bone: A
      Nonlinear 3-D Finite Element Analysis.
AB  - PURPOSE: To compare the stresses and displacements on perimplant bone generated
      by screw- and cement-retained prostheses using the finite element method.
      MATERIALS AND METHODS: Two models were constructed: partial fixed implant
      supported prostheses with three elements retained by screws (SFP) or cement
      (CFP). Vertical and oblique loads of 100 N were applied on the models. Bone was
      analyzed by the principal stresses sigma1 and sigma3. The displacement between
      the implant and the bone was identified by the penetration and gap. RESULTS:
      Results showed a similar pattern in the distribution of the principal stresses
      between both prostheses. Under the sigma1 stresses, the SFP showed similar values
      in the bone compared with the CFP. The analysis of the sigma3 showed stress peaks
      28% higher in the SFP, considering vertical and oblique loads. Displacement
      analysis showed a similar pattern and similar values between the prostheses for
      penetration and gap under both loads. CONCLUSIONS: There were no important
      differences in the sigma1 analysis and the displacement between the SFP and CFP.
      The differences in marginal bone level reported between SFP and CFP in some
      clinical studies may not be related to a mechanical factor.

PMID- 25985379
TI  - IL-6, IL-18, sIL-2R, and TNFalpha proinflammatory markers in depression and
      schizophrenia patients who are free of overt inflammation.
AB  - Major depressive disorder (MDD) and schizophrenia are associated with
      inflammatory processes. Studies have shown that these disorders exhibit increase
      in the level of one or more proinflammatory markers. However, these studies did
      not exclude patients with obvious inflammation (i.e., CRP>6mg/L). Therefore, a
      comprehensive study should include those inflammatory disorders. In the present
      study, the inflammatory natures of MDD and schizophrenia were investigated. To
      achieve this goal, serum levels of interleukin-6 (IL-6), interleukin-18 (IL-18),
      tumor necrosis factor alpha (TNFalpha), and soluble interleukin 2 receptor (sIL
      2R) in depressed and schizophrenic patients were obtained and compared with those
      of the control group. Results showed a significant increase (p<0.05) in serum
      levels of IL-6, IL-18, TNFalpha, and sIL-2R in MDD and schizophrenic patients
      compared with the control group. Also patients with schizophrenia group showed
      higher levels of the inflammatory markers than MDD and control groups. The
      current study concluded that the immunological response in the MDD and
      schizophrenic patients groups was significantly stimulated. These disorders may
      be considered an inflammatory disorder because of elevated levels of
      proinflammatory cytokines in spite of lacking an overt inflammation. Furthermore
      results of this study suggested the possibility of the use of anti-inflammatory
      drugs as adjuvant therapy in schizophrenic and depressive disorders. 

PMID- 25985380
TI  - The relationship between symptom relief and functional improvement during acute
      fluoxetine treatment for patients with major depressive disorder.
AB  - BACKGROUND: The purpose of this study was to compare the rate of symptom relief
      to functional improvement and examine the relationships between symptom relief
      and functional improvement during the acute phase of treatment. METHODS: A total
      of 131 acutely ill inpatients with major depressive disorder were enrolled to
      receive 20mg of fluoxetine daily for 6 weeks. Symptom severity, using the 17-item
      Hamilton Depression Rating Scale (HAMD-17), and functioning, using the Modified
      Work and Social Adjustment Scale (MWSAS), were measured regularly. The outcome
      measures were the HAMD-17 score and MWSAS score at weeks 1, 2, 3, 4, and 6. We
      compared the effect size and the reduction rate of HAMD-17 to those of MWSAS at
      week 1, 2, 3, 4, and 6. Structural equation modeling was used to examine
      relationships among the study variables. RESULTS: Of the 131 participants, 126
      had at least one post-baseline assessment at week 1 and were included in the
      analysis. The HAMD-17 had a larger effect size and reduction rate than the MWSAS
      at weeks 1, 2, 3, 4, and 6. Parsimonious model satisfied all indices of goodness
      of-fit (Chi-Square/df=1.479, TLI=0.978, CFI=0.986, RMSEA=0.062) and had all paths
      with significant path coefficients. MWSAS at week 0 predicted HAMD-17 at week 1.
      LIMITATION: This was an open-labeled study with small sample size. CONCLUSION:
      Depressive symptoms improved more quickly than functioning during the acute phase
      of treatment. Depressive symptoms and functional impairment are distinct domains,
      and should be assessed independently.

PMID- 25985381
TI  - Predictors of functional outcome after a manic episode.
AB  - BACKGROUND: The identification of functional outcome predictors after acute
      episodes of bipolar disorders (BD) may allow designing appropriate treatment
      aiming at restoring psychosocial functioning. Our objective was to identify the
      best functional outcome predictors at a 6-month follow-up after an index manic
      episode. METHODS: We conducted a naturalistic trial (MANACOR) focusing on the
      global burden of BD, with special emphasis on manic episode-associated costs. We
      observed patients with BD seen in services of four hospitals in Catalonia
      (Spain).The total sample included 169 patients with chronic DSM-IV-TR BD I
      suffering from an acute manic episode who were followed-up for 6 months. In this
      subanalysis we report the results of a stepwise multiple regression conducted by
      entering in the model those clinical and sociodemographic variables that were
      identified through preliminary bivariate Pearson correlations and using total
      scores on the Functioning Assessment Short Test (FAST) at the 6-month follow-up
      as the dependent variable. RESULTS: Number of previous depressive episodes
      (Beta=3.25; t=3.23; p=0.002), presence of psychotic symptoms during the manic
      index episode (Beta=7.007; t=2.2; p=0.031) and the Body Mass Index (BMI) at
      baseline (Beta=0.62; t=2.09; p=0.041) were best predictors of functional outcome
      after a manic episode. LIMITATIONS: The main limitations of this study include
      the retrospective assessment of the episodes, which can be a source of bias, and
      the 6-month follow-up might have been too short for assessing the course of a
      chronic illness. CONCLUSIONS: Psychotic symptoms at index episode, number of past
      depressive episodes, and BMI predict worse outcome after 6 months follow-up after
      a manic episode, and may constitute the target of specific treatment strategies.

PMID- 25985382
TI  - Aspirin and statin use and the subsequent development of depression in men and
      women: Results from a longitudinal population-based study.
AB  - OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying
      the well-established association between major depressive disorder (MDD) and
      increased cardiovascular morbidity. Both aspirin and statins have anti
      inflammatory properties, which may contribute to their preventive effect on
      cardiovascular diseases. Previous studies on the potentially preventive effect of
      these drugs on depression have provided inconsistent results. The aim of the
      present paper was to assess the prospective association between regular aspirin
      or statin use and the incidence of MDD. METHOD: This prospective cohort study
      included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from
      the general population of an urban area. Subjects underwent a thorough physical
      evaluation as well as semi-structured interviews investigating DSM-IV mental
      disorders at baseline and follow-up (mean duration 5.2 years). Analyses were
      adjusted for a wide array of potential confounders. RESULTS: Our main finding was
      that regular aspirin or statin use at baseline did not reduce the incidence of
      MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19;
      95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively).
      LIMITATIONS: Our study is not a randomized clinical trial and could not adjust
      for all potential confounding factors, information on aspirin or statin use was
      collected only for the 6 months prior to the evaluations, and the sample was
      restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do
      not support a large scale preventive treatment of depression using aspirin or
      statins in subjects aged from 35 to 66 years from the community.

PMID- 25985383
TI  - Prenatal antidepressant exposure and the risk of autism spectrum disorders in
      children. Are we looking at the fall of Gods?
AB  - Recent information suggests that antenatal exposure to psychotropics may impair
      child neurodevelopment. Thus, aim of this review is to examine systematically
      available literature investigating potential associations between prenatal use of
      selective serotonin reuptake inhibitors (SSRIs) and the risk of autism spectrum
      disorders (ASDs). METHODS: Medical literature published in English since 1988
      identified using MEDLINE/PubMed, EMBASE, SCOPUS, and The Cochrane Library. Search
      terms: antidepressants, autism (spectrum disorders), childhood, children,
      neurodevelopment, pregnancy, SSRIs. Searches were updated until March 5, 2015.
      RESULTS: Six out of eight reviewed articles confirm an association between
      antenatal SSRI exposure and an increased risk of ASDs in children. However, the
      epidemiologic evidence on the link between prenatal SSRI exposure and ASD risk
      must still be cautiously interpreted, because of potential biases of analyzed
      research. LIMITATIONS: Main limitations of reviewed studies include: lack of
      directly validated clinical evaluation, impossibility to identify women who
      really took the prescribed medications during pregnancy, no assessment of
      severity and course of symptoms in relation to the pregnancy, lack of information
      about unhealthy prenatal lifestyle behaviors. CONCLUSIONS: Despite such
      limitations, available data show that some signal exists suggesting that
      antenatal exposure to SSRIs may increase the risk of ASDs. Thus, there is an
      urgent need for further, large, well-designed research finalized to definitively
      assess the existence and the magnitude of this severe risk, thus confirming or
      denying that we are truly looking at "the fall of Gods", since for many years
      SSRIs have been considered the first-choice agents for treating antenatal
      depression (Gentile, 2014; Gentile, 2011a; Gentile, 2005).

PMID- 25985384
TI  - Constitutional Dynamic Chemistry-based New Concept of Molecular Beacons for High
      Efficient Development of Fluorescent Probes.
AB  - Inspired by the concept of constitutional dynamic chemistry, we propose a new and
      well-adaptable strategy for developing molecular beacon (MB)-like fluorescent
      probes. To demonstrate the strategy, we synthesized and used an amino group
      containing pyrenyl derivative of cholesterol (CP) for the construction of new
      fluorescent probes with EDTA and sulfuric acid. The probes as created were
      successfully used for n-hexane purity checking and Ba(2+)and Pb(2+)sensing,
      respectively. 

PMID- 25985385
TI  - Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New
      Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment.
AB  - OBJECTIVES: Assessments of care including quality assessments adjusted for
      physiological status should include the development of new morbidities as well as
      mortalities. We hypothesized that morbidity, like mortality, is associated with
      physiological dysfunction and could be predicted simultaneously with mortality.
      DESIGN: Prospective cohort study from December 4, 2011, to April 7, 2013.
      SETTING: General and cardiac/cardiovascular PICUs at seven sites. PATIENTS:
      Randomly selected PICU patients from their first PICU admission. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Among 10,078 admissions, the unadjusted
      morbidity rates (measured with the Functional Status Scale and defined as an
      increase of >= 3 from preillness to hospital discharge) were 4.6% (site range,
      2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%).
      Morbidity and mortality were significantly (p < 0.001) associated with
      physiological instability (measured with the Pediatric Risk of Mortality III
      score) in dichotomous (survival and death) and trichotomous (survival without new
      morbidity, survival with new morbidity, and death) models without covariate
      adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality
      III scores and then decreased at the highest Pediatric Risk of Mortality III
      values as potential morbidities became mortalities. The trichotomous model with
      covariate adjustments included age, admission source, diagnostic factors,
      baseline Functional Status Scale, and the Pediatric Risk of Mortality III score.
      The three-level goodness-of-fit test indicated satisfactory performance for the
      derivation and validation sets (p > 0.20). Predictive ability assessed with the
      volume under the surface was 0.50 +/- 0.019 (derivation) and 0.50 +/- 0.034
      (validation) (vs chance performance = 0.17). Site-level standardized morbidity
      ratios were more variable than standardized mortality ratios. CONCLUSIONS: New
      morbidities were associated with physiological status and can be modeled
      simultaneously with mortality. Trichotomous outcome models including both
      morbidity and mortality based on physiological status are suitable for research
      studies and quality and other outcome assessments. This approach may be
      applicable to other assessments presently based only on mortality.

PMID- 25985387
TI  - Effects of Inspiratory Pressure Rise Time and Hypoxic or Hypercapnic Breathing on
      Inspiratory Laryngeal Constrictor Muscle Activity During Nasal Pressure Support
      Ventilation.
AB  - OBJECTIVE: We previously reported the development of an active inspiratory
      laryngeal narrowing against ventilator insufflations when inspiratory pressure is
      increased during nasal pressure support ventilation in lambs. The present study
      aimed to further understand the factors involved in this inspiratory laryngeal
      narrowing. More specifically, we tested the hypothesis that a short inspiratory
      pressure rise time or a low PaCO2 level promotes inspiratory laryngeal narrowing
      observed in nasal pressure support ventilation. The effect of hypoxia was also
      assessed. DESIGN: Prospective, randomized, interventional study. SETTING: Animal
      research laboratory at the Faculty of Medicine and Health Sciences, Universite de
      Sherbrooke, Canada. SUBJECTS: Thirteen lambs aged 4-5 days. INTERVENTIONS:
      Polysomnographic recordings were performed in chronically instrumented lambs to
      study states of alertness, glottal muscle electrical activity, tracheal pressure,
      SpO2, and respiratory movements. Lambs were ventilated with progressively
      increasing levels of nasal pressure support ventilation (10/4, 15/4, and 20/4 cm
      H2O), using a broad range of inspiratory rise times from 0.05 to 0.4 s.
      Thereafter, either CO2 (PaCO2 = baseline value + 10 mm Hg) or N2 (PaO2 = 45-55 mm
      Hg) was added to the inspiratory line. MEASUREMENTS AND MAIN RESULTS: The
      percentage of respiratory cycles with phasic inspiratory activity of glottal
      constrictor muscle was measured and compared between the various experimental
      conditions. The different inspiratory pressure rise times tested did not alter
      the phasic inspiratory activity of glottal constrictor muscle during nasal
      pressure support ventilation. By contrast, this activity was virtually abolished
      by increasing PaCO2 in all lambs. Finally, no alterations in the phasic
      inspiratory activity of glottal constrictor muscle during nasal pressure support
      ventilation were observed during hypoxia. CONCLUSIONS: Active inspiratory
      laryngeal narrowing during nasal pressure support ventilation is not altered by
      inspiratory rise times ranging from 0.05 to 0.4 s or by moderate hypoxia, whereas
      a moderate increase in PaCO2 abolishes this activity.

PMID- 25985386
TI  - Effects of Sigh on Regional Lung Strain and Ventilation Heterogeneity in Acute
      Respiratory Failure Patients Undergoing Assisted Mechanical Ventilation.
AB  - OBJECTIVE: In acute respiratory failure patients undergoing pressure support
      ventilation, a short cyclic recruitment maneuver (Sigh) might induce reaeration
      of collapsed lung regions, possibly decreasing regional lung strain and improving
      the homogeneity of ventilation distribution. We aimed to describe the regional
      effects of different Sigh rates on reaeration, strain, and ventilation
      heterogeneity, as measured by thoracic electrical impedance tomography. DESIGN:
      Prospective, randomized, cross-over study. SETTING: General ICU of a single
      university-affiliated hospital. PATIENTS: We enrolled 20 critically ill patients
      intubated and mechanically ventilated with PaO2/FIO2 up to 300 mm Hg and positive
      end-expiratory pressure at least 5 cm H2O (15 with acute respiratory distress
      syndrome), undergoing pressure support ventilation as per clinical decision.
      INTERVENTIONS: Sigh was added to pressure support ventilation as a 35 cm H2O
      continuous positive airway pressure period lasting 3-4 seconds at different rates
      (no-Sigh vs 0.5, 1, and 2 Sigh(s)/min). All study phases were randomly performed
      and lasted 20 minutes. MEASUREMENTS AND MAIN RESULTS: In the last minutes of each
      phase, we measured arterial blood gases, changes in end-expiratory lung volume of
      nondependent and dependent regions, tidal volume reaching nondependent and
      dependent lung (Vtnondep and Vtdep), dynamic intratidal ventilation
      heterogeneity, defined as the average ratio of Vt reaching nondependent/Vt
      reaching dependent lung regions along inspiration (VtHit). With Sigh, oxygenation
      improved (p < 0.001 vs no-Sigh), end-expiratory lung volume of nondependent and
      dependent regions increased (p < 0.01 vs no-Sigh), Vtnondep showed a trend to
      reduction, and Vtdep significantly decreased (p = 0.11 and p < 0.01 vs no-Sigh,
      respectively). VtHit decreased only when Sigh was delivered at 0.5/min (p < 0.05
      vs no-Sigh), while it did not vary during the other two phases. CONCLUSIONS: Sigh
      decreases regional lung strain and intratidal ventilation heterogeneity. Our
      study generates the hypothesis that in ventilated acute respiratory failure
      patients, Sigh may enhance regional lung protection.

PMID- 25985388
TI  - 3D hierarchical assembly of ultrathin MnO2 nanoflakes on silicon nanowires for
      high performance micro-supercapacitors in Li- doped ionic liquid.
AB  - Building of hierarchical core-shell hetero-structures is currently the subject of
      intensive research in the electrochemical field owing to its potential for making
      improved electrodes for high-performance micro-supercapacitors. Here we report a
      novel architecture design of hierarchical MnO2@silicon nanowires (MnO2@SiNWs)
      hetero-structures directly supported onto silicon wafer coupled with Li-ion doped
      1-Methyl-1-propylpyrrolidinium bis(trifluromethylsulfonyl)imide (PMPyrrBTA) ionic
      liquids as electrolyte for micro-supercapacitors. A unique 3D mesoporous
      MnO2@SiNWs in Li-ion doped IL electrolyte can be cycled reversibly across a
      voltage of 2.2 V and exhibits a high areal capacitance of 13 mFcm(-2). The high
      conductivity of the SiNWs arrays combined with the large surface area of
      ultrathin MnO2 nanoflakes are responsible for the remarkable performance of these
      MnO2@SiNWs hetero-structures which exhibit high energy density and excellent
      cycling stability. This combination of hybrid electrode and hybrid electrolyte
      opens up a novel avenue to design electrode materials for high-performance micro
      supercapacitors.

PMID- 25985389
TI  - Transformation of electronic properties and structural phase transition from HfN
      to Hf3N4.
AB  - We report investigation of the structural phase transition and electronic
      properties of Hf(1-x)N (0 ? x ? 0.25) using first principles calculations. The
      defective NaCl-type structure with Hf vacancies (V(Hf)) is found to be stable
      over a large phase region. Hf3N4 with the Zr3N4-type structure is only stable in
      relative small region and readily destabilized when the stoichiometric ratio of N
      to Hf deviates from 4/3. The electronic and optic properties of Hf(1-x)N are
      controlled by the concentration of V(Hf). The full depletion of excess free
      electrons from Hf atoms results in the structural phase transition of Hf3N4.

PMID- 25985390
TI  - Spatial and temporal patterns in the seasonal distribution of toxic cyanobacteria
      in Western Lake Erie from 2002-2014.
AB  - Lake Erie, the world's tenth largest freshwater lake by area, has had recurring
      blooms of toxic cyanobacteria for the past two decades. These blooms pose
      potential health risks for recreation, and impact the treatment of drinking
      water. Understanding the timing and distribution of the blooms may aid in
      planning by local communities and resources managers. Satellite data provides a
      means of examining spatial patterns of the blooms. Data sets from MERIS (2002
      2012) and MODIS (2012-2014) were analyzed to evaluate bloom patterns and
      frequencies. The blooms were identified using previously published algorithms to
      detect cyanobacteria (~25,000 cells mL-1), as well as a variation of these
      algorithms to account for the saturation of the MODIS ocean color bands. Images
      were binned into 10-day composites to reduce cloud and mixing artifacts. The 13
      years of composites were used to determine frequency of presence of both
      detectable cyanobacteria and high risk (>100,000 cells mL-1) blooms. The bloom
      season according to the satellite observations falls within June 1 and October
      31. Maps show the pattern of development and areas most commonly impacted during
      all years (with minor and severe blooms). Frequencies during years with just
      severe blooms (minor bloom years were not included in the analysis) were examined
      in the same fashion. With the annual forecasts of bloom severity, these frequency
      maps can provide public water suppliers and health departments with guidance on
      the timing of potential risk. 

PMID- 25985391
TI  - Zinc-Mediated Carbene Insertion to C-Cl Bonds of Chloromethanes and Isolable
      Zinc(II) Isocyanide Adducts.
AB  - The zinc adduct {[HB(3,5-(CF3)2Pz)3]Zn}(+), which was generated from [HB(3,5
      (CF3)2Pz)3]ZnEt and [Ph3C]{B[3,5-(CF3)2C6H3]4}, catalyzes the activation of C
      halogen bonds of chloromethanes via carbene insertion. Ethyl diazoacetate serves
      as the carbene precursor. The presence of {[HB(3,5-(CF3)2Pz)3]Zn}(+) in the
      reaction mixture was confirmed by obtaining {[HB(3,5-(CF3)2Pz)3]Zn(CN(t)Bu)3}(+)
      using CN(t)Bu as a trapping agent. {[HB(3,5-(CF3)2Pz)3]Zn(CN(t)Bu)3}(+) loses one
      zinc-bound CN(t)Bu easily to produce five-coordinate {[HB(3,5
      (CF3)2Pz)3]Zn(CN(t)Bu)2}(+). 

PMID- 25985392
TI  - Effectiveness of the Incredible Years Parenting Program for Families with
      Socioeconomically Disadvantaged and Ethnic Minority Backgrounds.
AB  - Families with socioeconomically disadvantaged and ethnic minority backgrounds are
      often hard to reach for the prevention and treatment of disruptive child behavior
      problems. We examined whether the Incredible Years parenting intervention can
      successfully reach and benefit families with socioeconomic disadvantaged and
      ethnic minority backgrounds in the Netherlands. One hundred fifty-four families
      from a wide range of socioeconomic and ethnic backgrounds were recruited in an
      outpatient clinic for child and adolescent psychiatry and in elementary schools
      serving deprived neighborhoods. Families were randomly assigned to the BASIC
      Incredible Years parenting intervention or a waiting list control condition.
      Children were 3-8 years old (M = 5.59, SD = 1.35; 62% boys, 66% ethnic
      minorities) and 65% of the children met Diagnostic and Statistical Manual of
      Mental Disorders (4th ed., text rev.) criteria for oppositional defiant disorder,
      conduct disorder, and/or attention-deficit hyperactivity disorder. Incredible
      Years reduced parent-reported disruptive child behavior and teacher-reported
      hyperactive and inattentive child behavior and increased parent-reported use of
      praise and incentives and reduced harsh and inconsistent discipline. Incredible
      Years did not affect parent-reported hyperactive and inattentive child behavior;
      teacher-reported child conduct problems; and parent-reported use of appropriate
      discipline techniques, clear expectations, physical punishment, and parenting
      stress. Of importance, the effectiveness of Incredible Years did not differ
      across families with different socioeconomic and ethnic backgrounds. Effects were
      maintained at 3-month follow-up. This study shows that socioeconomically
      disadvantaged and ethnic minority families in disadvantaged neighborhoods can be
      engaged in and benefit from parenting interventions to reduce disruptive child
      behavior.

PMID- 25985395
TI  - Impact of a comprehensive pharmacist medication-therapy management service.
AB  - OBJECTIVE: This proof of concept study aimed to determine whether a pharmacist
      managed medication therapy management (MTM) program in a private endocrinologist
      physician's practice reduced healthcare services utilization and related costs 6
      months after patients' discharge from an institution with a transition of care
      service. METHODS: Patients were included in the study if they were English
      speaking, ages >18 years, had type 1 or 2 diabetes, and had a recent transition
      of care experience (inpatient hospital stay or emergency department/urgent
      care/paramedic or other acute care visit). The study had a non-randomized design
      where intervention patients, enrolled July 1, 2012-September 30, 2013, were
      administered MTM at four visits over 6 months and were compared to historical
      control patients with available electronic medical records from August 8, 2008 to
      March 15, 2012. The primary study end-point was the rate of 30-day hospital
      readmissions, as related to the reason for the index admission. Secondary end
      points included the cumulative rate of all-cause hospitalizations, emergency
      department, paramedic and urgent care visits at 30, 60, 90, and 180 days post
      discharge as well as imputed total costs, including prescription medication
      costs, at 180 days. Propensity score weights were constructed to balance
      covariate characteristics between the intervention and control groups. Weighted
      multivariate negative binomial and generalized linear regressions were used to
      model cumulative utilization rates and log-transformed costs, respectively.
      RESULTS: The intervention (n = 28) and control (n = 73) groups had 0% hospital
      readmissions at 30 days post-discharge. In propensity score weighted multivariate
      analyses, cumulative utilization rate was not different between the two groups
      (IRR = 1.61, p = 0.72 at 180 days) while costs in the intervention group were
      lower but not statistically different (cost ratio = 0.65, p = 0.13 at 180 days).
      CONCLUSIONS: Further studies should investigate whether the integration of
      pharmacists in transition of care models could reduce readmission and healthcare
      utilization rates post-discharge.

PMID- 25985396
TI  - Soliton nanoantennas in two-dimensional arrays of quantum dots.
AB  - We consider two-dimensional (2D) arrays of self-organized semiconductor quantum
      dots (QDs) strongly interacting with electromagnetic field in the regime of Rabi
      oscillations. The QD array built of two-level states is modelled by two coupled
      systems of discrete nonlinear Schrodinger equations. Localized modes in the form
      of single-peaked fundamental and vortical stationary Rabi solitons and self
      trapped breathers have been found. The results for the stability, mobility and
      radiative properties of the Rabi modes suggest a concept of a self-assembled 2D
      soliton-based nano-antenna, which is stable against imperfections In particular,
      we discuss the implementation of such a nano-antenna in the form of surface
      plasmon solitons in graphene, and illustrate possibilities to control their
      operation by means of optical tools. 

PMID- 25985393
TI  - Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming.
AB  - We describe robust induction of autophagy during the reprogramming of mouse
      fibroblasts to induced pluripotent stem cells by four reprogramming factors
      (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of
      p53 activation, and is mediated by the synergistic downregulation of mechanistic
      target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related
      genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of
      autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4
      inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by
      promoting cell reshaping (mitochondrial remodelling and cell size reduction). On
      the other hand, mTORC1 paradoxically impairs reprogramming by triggering
      autophagy. Autophagy does not participate in cell reshaping in reprogramming but
      instead degrades p62, whose accumulation in autophagy-deficient cells facilitates
      reprogramming. Our results thus reveal a complex signalling network involving
      mTORC1 inhibition and autophagy induction in the early phase of reprogramming,
      whose delicate balance ultimately determines reprogramming efficiency. 

PMID- 25985394
TI  - Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.
AB  - Pancreatic ductal adenocarcinomas (PDACs) are highly metastatic with poor
      prognosis, mainly due to delayed detection. We hypothesized that intercellular
      communication is critical for metastatic progression. Here, we show that PDAC
      derived exosomes induce liver pre-metastatic niche formation in naive mice and
      consequently increase liver metastatic burden. Uptake of PDAC-derived exosomes by
      Kupffer cells caused transforming growth factor beta secretion and upregulation
      of fibronectin production by hepatic stellate cells. This fibrotic
      microenvironment enhanced recruitment of bone marrow-derived macrophages. We
      found that macrophage migration inhibitory factor (MIF) was highly expressed in
      PDAC-derived exosomes, and its blockade prevented liver pre-metastatic niche
      formation and metastasis. Compared with patients whose pancreatic tumours did not
      progress, MIF was markedly higher in exosomes from stage I PDAC patients who
      later developed liver metastasis. These findings suggest that exosomal MIF primes
      the liver for metastasis and may be a prognostic marker for the development of
      PDAC liver metastasis. 

PMID- 25985397
TI  - Aminomaleimide fluorophores: a simple functional group with bright, solvent
      dependent emission.
AB  - Amino-substituted maleimides form a new class of highly emissive compounds, with
      large Stokes shifts (>100 nm) and high quantum yields (up to ~60%). Emission is
      responsive to the maleimide's environment with both a red-shift, and quenching,
      observed in protic polar solvents. Aminomaleimides are easily functionalised,
      providing a versatile fluorescent probe. 

PMID- 25985398
TI  - Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes
      via CXCR4.
AB  - OBJECTIVES: HIV reservoir in the brain represents a major barrier for curing HIV
      infection. As the most abundant, long-lived cell type, astrocytes play a critical
      role in maintaining the reservoir; however, the mechanism of infection remains
      unknown. Here, we determine how viral transmission occurs from HIV-infected
      lymphocytes to astrocytes by cell-to-cell contact. DESIGN AND METHODS: Human
      astrocytes were exposed to HIV-infected lymphocytes and monitored by live
      imaging, confocal microscopy, transmission and three-dimensional electron
      microscopy. A panel of receptor antagonists was used to determine the mechanism
      of viral entry. RESULTS: We found that cell-to-cell contact resulted in efficient
      transmission of X4 or X4R5-using viruses from T lymphocytes to astrocytes. In co
      cultures of astrocytes with HIV-infected lymphocytes, the interaction occurred
      through a dynamic process of attachment and detachment of the two cell types.
      Infected lymphocytes invaginated into astrocytes or the contacts occurred via
      filopodial extensions from either cell type, leading to the formation of
      virological synapses. In the synapses, budding of immature or incomplete HIV
      particles from lymphocytes occurred directly onto the membranes of astrocytes.
      This cell-to-cell transmission could be almost completely blocked by anti-CXCR4
      antibody and its antagonist, but only partially inhibited by anti-CD4, ICAM1
      antibodies. CONCLUSION: Cell-to-cell transmission was mediated by a unique
      mechanism by which immature viral particles initiated a fusion process in a CXCR4
      dependent, CD4-independent manner. These observations have important implications
      for developing approaches to prevent formation of HIV reservoirs in the brain.

PMID- 25985399
TI  - Associations of common variants in the BST2 region with HIV-1 acquisition in
      African American and European American people who inject drugs.
AB  - OBJECTIVE: The bone marrow stromal cell antigen 2 (BST2) gene encodes a host
      restriction factor that acts as an innate immune sensor of HIV-1 exposure and
      suppresses release of HIV-1 particles. We aimed to identify associations of
      variants in the BST2 gene region with HIV-1 acquisition and disease progression.
      DESIGN/METHODS: Using HIV+ cases and HIV- controls from the Urban Health Study
      (n=3136 African Americans and European Americans who inject drugs), we tested 470
      variants in BST2 and its flanking regions for association with HIV-1 acquisition
      and log-transformed viral load. RESULTS: We found that the single nucleotide
      polymorphism (SNP) rs113189798 surpassed the P value threshold corrected for
      multiple testing. The rs113189798-G allele (frequency=16% in African Americans,
      4% in European Americans) was associated with increased HIV-1 acquisition risk
      (meta-analysis P=1.43 * 10): odds ratio (95% confidence interval) of 1.22 (1.01
      1.49) in African Americans and 2.17 (1.43-3.33) in European Americans. We also
      found that the previously reported rs12609479-A allele (frequency=35% in African
      Americans, 81% in European Americans) was nominally associated with decreased
      risk of acquiring HIV-1 in our study (meta-analysis P=0.036). Rs12609479-A is
      predicted to increase BST2 expression and thereby decrease risk of acquiring HIV
      1. Rs113189798 and rs12609479 were only weakly correlated [square of the
      correlation coefficient (r)=0.2-0.4] and represented distinct association
      signals. None of our tested variants were significantly associated with log
      transformed viral load among the HIV-infected cases. CONCLUSION: Our findings
      support BST2 as a genetic susceptibility factor for HIV-1 acquisition:
      identifying a novel SNP association for rs13189798 and linking the previously
      reported regulatory SNP rs12609479 to HIV-1 acquisition.

PMID- 25985401
TI  - Cross-reactivity between darunavir and trimethoprim-sulfamethoxazole in HIV
      infected patients.
AB  - OBJECTIVE: Both darunavir (DRV) and trimethoprim-sulfamethoxazole (TMP-SMX) carry
      a sulfonamide moiety and a warning for this cross-reactivity is given in the
      label of DRV. The aim of this study was to investigate the potential cross
      reactivity between both drugs. DESIGN: Retrospective cohort study with a nested
      case-control study. METHODS: HIV-infected patients that received DRV-containing
      antiretroviral therapy at any time during the period of their HIV infection were
      included. Patients with no history of TMP-SMX use were excluded. The incidence of
      a DRV allergy, according to the Naranjo probability scale, was investigated in
      patients with an allergy to TMP-SMX compared with those without such an allergy.
      In order to identify possible risk factors associated with a DRV allergy among
      patients allergic to TMP-SMX, a nested case-control study was subsequently
      performed. RESULTS: A total of 405 patients were included, of whom 79 (17.5%) had
      a history of allergy to TMP-SMX. A DRV allergy was seen in four patients (5.1%)
      with a TMP-SMX allergy compared with four (1.2%) without a TMP-SMX allergy (P =
      0.05). Patients with a TMP-SMX allergy were at higher risk for a DRV allergy
      (odds ratio 4.29; 95% confidence interval, 1.05-17.56). No additional risk
      factors for a DRV allergy among patients allergic to TMP-SMX were identified in
      the nested case-control study. CONCLUSION: Although DRV allergy is uncommon,
      making cross-reactivity with TMP-SMX a rare clinical problem, it appears to exist
      more often in the background of a TMP-SMX allergy.

PMID- 25985400
TI  - High level of APOBEC3F/3G editing in HIV-2 DNA vif and pol sequences from
      antiretroviral-naive patients.
AB  - OBJECTIVE: In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase
      activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV
      2 sequences remains unknown. The objective of this study was to assess the level
      of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. METHODS:
      Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from
      antiretroviral-naive patients included in the French Agence Nationale de
      Recherches sur le SIDA et les hepatites virales CO5 HIV-2 cohort. Hypermutated
      sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences
      from Genbank were also assessed. RESULTS: Among 82 antiretroviral-naive HIV-2
      infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral
      defective sequences in HIV-2 groups A and B, respectively. A lower proportion of
      defective sequences was observed in protease-reverse transcriptase region. A
      higher median number of G-to-A mutations was observed in HIV-2 group B than in
      group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P =
      0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif
      defective sequences was observed in HIV-2 group A (P = 0.00001) and group B
      sequences (P = 0.013). CONCLUSION: We showed for the first time a high level of
      APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our
      study reported a group effect with a significantly higher level of APOBEC3F/3G
      editing in HIV-2 group B than in group A sequences.

PMID- 25985402
TI  - Impact of nucleic acid testing relative to antigen/antibody combination
      immunoassay on the detection of acute HIV infection.
AB  - OBJECTIVE: To assess the addition of HIV nucleic acid testing (NAT) to fourth
      generation (4thG) HIV antigen/antibody combination immunoassay in improving
      detection of acute HIV infection (AHI). METHODS: Participants attending a major
      voluntary counseling and testing site in Thailand were screened for AHI using
      4thG HIV antigen/antibody immunoassay and sequential less sensitive HIV antibody
      immunoassay. Samples nonreactive by 4thG antigen/antibody immunoassay were
      further screened using pooled NAT to identify additional AHI. HIV infection
      status was verified following enrollment into an AHI study with follow-up visits
      and additional diagnostic tests. RESULTS: Among 74 334 clients screened for HIV
      infection, HIV prevalence was 10.9% and the overall incidence of AHI (N = 112)
      was 2.2 per 100 person-years. The inclusion of pooled NAT in the testing
      algorithm increased the number of acutely infected patients detected, from 81 to
      112 (38%), relative to 4thG HIV antigen/antibody immunoassay. Follow-up testing
      within 5 days of screening marginally improved the 4thG immunoassay detection
      rate (26%). The median CD4 T-cell count at the enrollment visit was 353 cells/MUl
      and HIV plasma viral load was 598 289 copies/ml. CONCLUSION: The incorporation of
      pooled NAT into the HIV testing algorithm in high-risk populations may be
      beneficial in the long term. The addition of pooled NAT testing resulted in an
      increase in screening costs of 22% to identify AHI: from $8.33 per screened
      patient to $10.16. Risk factors of the testing population should be considered
      prior to NAT implementation given the additional testing complexity and costs.

PMID- 25985403
TI  - The impact of adherence to preexposure prophylaxis on the risk of HIV infection
      among people who inject drugs.
AB  - OBJECTIVE: To describe participant adherence to daily oral tenofovir in an HIV
      preexposure prophylaxis (PrEP) trial, examine factors associated with adherence,
      and assess the impact of adherence on the risk of HIV infection. DESIGN: The
      Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial
      conducted among people who inject drugs, 2005-2012. METHODS: Participants chose
      daily visits or monthly visits. Study nurses observed participants swallow study
      drug and both initialed a diary. We assessed adherence using the diary. We
      examined adherence by age group and sex and used logistic regression to evaluate
      demographics and risk behaviors as predictors of adherence and Cox regression to
      assess the impact of adherence on the risk of HIV infection. RESULTS: A total of
      2413 people enrolled and contributed 9665 person-years of follow-up (mean 4.0
      years, maximum 6.9 years). The risk of HIV infection decreased as adherence
      improved, from 48.9% overall to 83.5% for those with at least 97.5% adherence. In
      multivariable analysis, men were less adherent than women (P = 0.006) and
      participants 20-29 years old (P < 0.001) and 30-39 years old (P = 0.01) were less
      adherent than older participants. Other factors associated with poor adherence
      included incarceration (P = 0.02) and injecting methamphetamine (P = 0.04).
      CONCLUSION: In this HIV PrEP trial among people who inject drugs, improved
      adherence to daily tenofovir was associated with a lower risk of HIV infection.
      This is consistent with trials among MSM and HIV-discordant heterosexual couples
      and suggests that HIV PrEP can provide a high level of protection from HIV
      infection.

PMID- 25985404
TI  - Hair concentrations of antiretrovirals predict viral suppression in HIV-infected
      pregnant and breastfeeding Ugandan women.
AB  - OBJECTIVE: Hair concentrations are a noninvasive measure of cumulative
      antiretroviral exposure and the strongest predictor of viral suppression in large
      cohorts of nonpregnant patients. We examined hair concentrations of
      antiretrovirals in relation to virologic outcomes in pregnant and breastfeeding
      women for the first time. DESIGN AND METHODS: The Prevention of Malaria and HIV
      Disease in Tororo trial (NCT00993031) enrolled HIV-infected pregnant Ugandan
      women at 12-28 weeks gestation who were randomized to lopinavir or efavirenz
      based antiretroviral therapy (ART). Small hair samples were collected at 30-34
      weeks gestation and 10-25 weeks postpartum. Efavirenz and lopinavir hair
      concentrations were measured via liquid chromatography/tandem mass spectrometry.
      Multivariate logistic regression models examined predictors of viral suppression
      (HIV-1 RNA <=400 copies/ml) at delivery and 24 weeks postpartum. RESULTS: Among
      325 women, median CD4 cell count was 366 cells/MUl (interquartile range 270-488)
      at ART initiation. Mean self-reported 3-day adherence was greater than 97% in
      each arm. Viral suppression was achieved by 98.0% (efavirenz) and 87.4%
      (lopinavir) at delivery. At 24 weeks postpartum, 92.5% (efavirenz) and 90.6%
      (lopinavir) achieved viral suppression; 88% of women were breastfeeding. In
      multivariate models including self-reported adherence and pretreatment HIV-1 RNA,
      antiretroviral hair concentrations were the strongest predictor of viral
      suppression at delivery [efavirenz: adjusted odds ratio (aOR) 1.86 per doubling
      in concentration, 95% confidence interval (CI) 1.14-3.1, P = 0.013; lopinavir:
      aOR 1.90, 95% CI 1.33-2.7, P = 0.0004] and 24 weeks postpartum (efavirenz: aOR
      1.81, 95% CI 1.22-2.7, P = 0.003; lopinavir: aOR 1.53, 95% CI 1.05-2.2, P =
      0.026). CONCLUSION: Antiretroviral hair concentrations represent an innovative
      tool that strongly predicts viral suppression among HIV-infected childbearing
      women during the critical periods of delivery and breastfeeding.

PMID- 25985406
TI  - Is statin preventing cancer in HIV-1 infected individuals? An inappropriate
      methodology is a more likely explanation.

PMID- 25985405
TI  - Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on
      the health of infants born to HIV-infected mothers.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection can be acquired in utero or
      postnatally through horizontal transmission and breastfeeding. The effect of
      postnatal CMV infection on postnatal HIV transmission is unknown. METHODS: The
      Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi,
      randomized 2369 mothers and their infants to three antiretroviral prophylaxis
      arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of
      breastfeeding, followed by weaning. Stored plasma and peripheral blood
      mononuclear cell specimens were available for 492 infants at 24 weeks and were
      tested with CMV PCR. Available samples from infants who were CMV PCR-positive at
      24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24
      weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used
      to determine if CMV infection was associated with infant morbidity, mortality, or
      postnatal HIV acquisition. RESULTS: At 24 weeks of age, CMV DNA was detected in
      345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%,
      and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at
      24 weeks was associated with subsequent HIV acquisition through breastfeeding or
      infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05).
      CONCLUSION: Most breastfed infants of HIV-infected mothers in this resource
      limited setting are infected with CMV by 24 weeks of age. Early CMV infection may
      be a risk factor for subsequent infant HIV infection through breastfeeding,
      pointing to the need for comprehensive approaches in order to achieve elimination
      of breastfeeding transmission of HIV.

PMID- 25985407
TI  - Is statin preventing cancer in HIV-1 infected individuals? An inappropriate
      methodology is a more likely explanation: authors' reply.

PMID- 25985408
TI  - Immortal time bias.

PMID- 25985409
TI  - Immortal time bias: authors' reply.

PMID- 25985410
TI  - Transmitted antiretroviral resistance in a large HIV directorate 2011-2014: a
      response.

PMID- 25985411
TI  - Antiretroviral nanoparticles: the future is now: authors' response to editorial
      comments.

PMID- 25985412
TI  - The Wells Deep Vein Thrombosis Score for Inpatients: Not the Right Tool for the
      Job.

PMID- 25985413
TI  - The evolution of the gut microbiota in the giant and the red pandas.
AB  - The independent dietary shift from carnivore to herbivore with over 90% being
      bamboo in the giant and the red pandas is of great interests to biologists.
      Although previous studies have shown convergent evolution of the giant and the
      red pandas at both morphological and molecular level, the evolution of the gut
      microbiota in these pandas remains largely unknown. The goal of this study was to
      determine whether the gut microbiota of the pandas converged due to the same
      diet, or diverged. We characterized the fecal microbiota from these two species
      by pyrosequencing the 16S V1-V3 hypervariable regions using the 454 GS FLX
      Titanium platform. We also included fecal samples from Asian black bears, a
      species phylogenetically closer to the giant panda, in our analyses. By analyzing
      the microbiota from these 3 species and those from other carnivores reported
      previously, we found the gut microbiotas of the giant pandas are distinct from
      those of the red pandas and clustered closer to those of the black bears. Our
      data suggests the divergent evolution of the gut microbiota in the pandas. 

PMID- 25985414
TI  - Comparative analysis of potassium deficiency-responsive transcriptomes in low
      potassium susceptible and tolerant wheat (Triticum aestivum L.).
AB  - Potassium (K(+)) deficiency as a common abiotic stress can inhibit the growth of
      plants and thus reduce the agricultural yields. Nevertheless, scarcely any
      development has been promoted in wheat transcriptional changes under K(+)
      deficiency. Here we investigated root transcriptional changes in two wheat
      genotypes, namely, low-K(+) tolerant "Tongzhou916" and low-K(+) susceptible
      "Shiluan02-1". There were totally 2713 and 2485 probe sets displayed expression
      changes more than 1.5-fold in Tongzhou916 and Shiluan02-1, respectively. Low-K(+)
      responsive genes mainly belonged to the categories as follows: metabolic process,
      cation binding, transferase activity, ion transporters and so forth. We made a
      comparison of gene expression differences between the two wheat genotypes. There
      were 1321 and 1177 up-regulated genes in Tongzhou916 and Shiluan02-1,
      respectively. This result indicated that more genes took part in acclimating to
      low-K(+) stress in Tongzhou916. In addition, there were more genes associated
      with jasmonic acid, defense response and potassium transporter up-regulated in
      Tongzhou916. Moreover, totally 19 genes encoding vacuolar H(+)-pyrophosphatase,
      ethylene-related, auxin response, anatomical structure development and nutrient
      reservoir were uniquely up-regulated in Tongzhou916. For their important role in
      root architecture, K(+) uptake and nutrient storage, unique genes above may make
      a great contribution to the strong low-K(+) tolerance in Tongzhou916. 

PMID- 25985415
TI  - Hydrothermal fractionation of woody biomass: Lignin effect on sugars recovery.
AB  - Subcritical water was employed to fractionate woody biomass into carbohydrates
      and lignin. Nine urban trees species (hardwood and softwood) from Spain were
      studied. The experiments were carried out in a semi-continuous reactor at 250 
      degrees C for 64 min. The hemicellulose and cellulose recovery yields were
      between 30%wt. and 80%wt. while the lignin content in the solid product ranged
      between 32%wt. and 92%wt. It was observed that an increment of solubilized lignin
      disfavored the hydrolysis of hemicelluloses. It was determined that the maximum
      extraction of hemicellulose was achieved at 20 min of solid reaction time while
      the extraction of celluloses not exhibited a maximum value. The hydrolysis of
      hemicellulose and cellulose would be governed by the hydrolysis kinetic and the
      polymers accessibility. In addition, the extraction of hemicellulose was
      negatively affected by the lignin content in the raw material while cellulose
      hydrolysis was not affected by this parameter.

PMID- 25985416
TI  - Crude oil biodegradation aided by biosurfactants from Pseudozyma sp. NII 08165 or
      its culture broth.
AB  - The aim of this work was to evaluate the biosurfactants produced by the yeast
      Pseudozyma sp. NII 08165 for enhancing the degradation of crude oil by a model
      hydrocarbon degrading strain, Pseudomonas putida MTCC 1194. Pseudozyma
      biosurfactants were supplemented at various concentrations to the P. putida
      culture medium containing crude oil as sole carbon source. Supplementation of the
      biosurfactants enhanced the degradation of crude oil by P. putida; the maximum
      degradation of hydrocarbons was observed with a 2.5 mg L(-1) supplementation of
      biosurfactants. Growth inhibition constant of the Pseudozyma biosurfactants was
      11.07 mg L(-1). It was interesting to note that Pseudozyma sp. NII 08165 alone
      could also degrade diesel and kerosene. Culture broth of Pseudozyma containing
      biosurfactants resulted up to ~46% improvement in degradation of C10-C24 alkanes
      by P. putida. The enhancement in degradation efficiency of the bacterium with the
      culture broth supplementation was even more pronounced than that with relatively
      purer biosurfactants.

PMID- 25985417
TI  - Substantial improvement of perovskite solar cells stability by pinhole-free hole
      transport layer with doping engineering.
AB  - We fabricated perovskite solar cells using a triple-layer of n-type doped,
      intrinsic, and p-type doped 2,2',7,7'-tetrakis(N,N'-di-p-methoxyphenylamine)-9,9'
      spirobifluorene (spiro-OMeTAD) (n-i-p) as hole transport layer (HTL) by vacuum
      evaporation. The doping concentration for n-type doped spiro-OMeTAD was optimized
      to adjust the highest occupied molecular orbital of spiro-OMeTAD to match the
      valence band maximum of perovskite for efficient hole extraction while
      maintaining a high open circuit voltage. Time-dependent solar cell performance
      measurements revealed significantly improved air stability for perovskite solar
      cells with the n-i-p structured spiro-OMeTAD HTL showing sustained efficiencies
      even after 840 h of air exposure. 

PMID- 25985418
TI  - DNA immunoprecipitation semiconductor sequencing (DIP-SC-seq) as a rapid method
      to generate genome wide epigenetic signatures.
AB  - Modification of DNA resulting in 5-methylcytosine (5 mC) or 5
      hydroxymethylcytosine (5hmC) has been shown to influence the local chromatin
      environment and affect transcription. Although recent advances in next generation
      sequencing technology allow researchers to map epigenetic modifications across
      the genome, such experiments are often time-consuming and cost prohibitive. Here
      we present a rapid and cost effective method of generating genome wide DNA
      modification maps utilising commercially available semiconductor based technology
      (DNA immunoprecipitation semiconductor sequencing; "DIP-SC-seq") on the Ion
      Proton sequencer. Focussing on the 5hmC mark we demonstrate, by directly
      comparing with alternative sequencing strategies, that this platform can
      successfully generate genome wide 5hmC patterns from as little as 500 ng of
      genomic DNA in less than 4 days. Such a method can therefore facilitate the rapid
      generation of multiple genome wide epigenetic datasets.

PMID- 25985419
TI  - In-situ deposition of silver-iron oxide nanoparticles on the surface of fly ash
      for water purification.
AB  - In this study, a fly ash based composite, Ag-iron oxide/fly ash, was synthesized
      via a facile one-pot hydrothermal process using fly ash, ferrous chloride, and
      silver nitrate as precursors. Field emission scanning electron microscopy (FE
      SEM), EDX, transmission electron microscopy (TEM), X-ray diffraction (XRD),
      Fourier transform infra-red spectroscopy (FTIR), Photoluminescence (PL) and
      Brunauer-Emmett-Teller (BET) surface area measurement confirmed the formation of
      composite particle. FA provided a suitable surface for the in-situ deposition of
      Fe3O4 and Ag NPs during hydrothermal treatment. As a result, the particle size of
      Fe3O4 and Ag NPs was sufficiently decreased, and the surface area of the NPs as
      well as, a whole matrix was increased. The antimicrobial activity of the
      composite was accessed by Escherichia coli inhibition assay. Lead(II) ion
      adsorption efficiency of the composite was analyzed from a series of batch
      adsorption experiments (the effects of concentration, contact time, pH and
      adsorbent dose on the adsorption of Pb(II) ion from aqueous solution). Results
      indicated that as-synthesized composite has high antibacterial capacity, and the
      metal ions uptake efficiency compared to fly ash particle. Furthermore,
      incorporation Fe3O4 NPs onto the fly ash make it easily separable from a reaction
      system using an external magnet. The composite synthesis protocol is a simple
      method that utilizes a readily available industrial byproduct to produce a unique
      composite for environmental remediation. 

PMID- 25985421
TI  - Impact of air and water vapor environments on the hydrophobicity of surfaces.
AB  - HYPOTHESIS: Droplet wettability and mobility play an important role in dropwise
      condensation heat transfer. Heat exchangers and heat pipes operate at liquid
      vapor saturation. We hypothesize that the wetting behavior of liquid water on
      microstructures surrounded by pure water vapor differs from that for water
      droplets in air. EXPERIMENTS: The static and dynamic contact angles and contact
      angle hysteresis of water droplets were measured in air and pure water vapor
      environments inside a pressure vessel. Pressures ranged from 60 to 1000 mbar,
      with corresponding saturation temperatures between 36 and 100 degrees C. The
      wetting behavior was studied on four hydrophobic surfaces: flat Teflon-coated,
      micropillars, micro-scale meshes, and nanoparticle-coated with hierarchical micro
      and nanoscale roughness. FINDINGS: Static advancing contact angles are 9 degrees
      lower in the water vapor environment than in air on a flat surface. One
      explanation for this reduction in contact angles is water vapor adsorption to the
      Teflon. On microstructured surfaces, the vapor environment has little effect on
      the static contact angles. In all cases, variations in pressure and temperature
      do not influence the wettability and mobility of the water droplets. In most
      cases, advancing contact angles increase and contact angle hysteresis decreases
      when the droplets are sliding or rolling down an inclined surface.

PMID- 25985420
TI  - Enhanced electroactive and mechanical properties of poly(vinylidene fluoride) by
      controlling crystallization and interfacial interactions with low loading
      polydopamine coated BaTiO3.
AB  - Poly(vinylidene fluoride) (PVDF) is a semi-crystalline polymer and the polar beta
      phase of PVDF shows superb electroactive properties. In order to enhance the beta
      phase of PVDF, extreme low content of BaTiO3 nanoparticles (BT-NPs) coated with
      polydopamine (Pdop) were incorporated into PVDF matrix by solution casting. The
      beta-phase of the resulting PVDF nanocomposites film was dramatically increased
      and the d33 value reached 34.3+/-0.4 pCN(-1). It is found that the Pdop layer
      could improve the dispersibility and stability of the BT NPs in solution and
      endow the BT NPs good dispersity in the PVDF matrix. Moreover, the interfacial
      interaction between PVDF chains and the surface of BT-Pdop nanoparticles (BT-Pdop
      NPs) were revealed, in which the CF2 groups on PVDF could interact with the
      electron-rich plane of aromatic ring of Pdop moiety. This interaction, led to the
      increase of the crystallization activation energy as derived from the DSC
      nonisothermal crystallization measurement. The alpha-beta crystal transformation,
      organization of interfacial interactions as well as the prevention of
      agglomeration of BT-NPs confer the improvement of mechanical and thermal
      properties of PVDF, such as toughness, tensile strength, elongation at break, and
      thermal conductivity.

PMID- 25985422
TI  - Toward surfactant-free and water-free microemulsions.
AB  - It was recently demonstrated that a nano-clustering was present in the monophasic
      "pre-Ouzo" region of ternary liquid mixtures without surfactants. The goal of
      this work is to check if this nano-clustering is also present in the surfactant
      free and water-free "green" microemulsions glycerol/ethanol/1-octanol and deep
      eutectic solvent/tetrahydrofurfuryl alcohol/diethyl adipate. The deep eutectic
      solvents used instead of water were ethylene glycol-choline chloride (molar ratio
      4-1) and urea-choline chloride (molar ratio 2-1). To our knowledge this is the
      first time that deep eutectic solvents were used to formulate microemulsions. The
      surfactant-free and water-free microemulsions were studied using phase diagrams,
      dynamic light scattering, and small-angle X-ray scattering. The presence of
      aggregate fluctuations was demonstrated and they were found to be independent of
      molecular critical fluctuations, except when approaching the critical point where
      the critical phenomenon is superimposed to the signal. These structures have
      similarities to classical microemulsions but, in contrast to them, without having
      a sharp interface between the non-miscible phases, much as it was the case for
      systems previously investigated like water/ethanol/oil, where the oil was 1
      octanol, fragrance molecules, or mosquito repellents. 

PMID- 25985423
TI  - Synthesis of core-shell SiO2@MgO with flower like morphology for removal of
      crystal violet in water.
AB  - In this study, we report a facile and effective route to synthesize core-shell
      SiO2@MgO with flower like morphology, which the shell is assembled by magnesium
      oxide nanosheets. The SiO2@MgO composite (SMC) was characterized by X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), energy-dispersive X-ray spectrometry (EDX), X-ray fluorescence
      (XRF) and N2 adsorption-desorption techniques. The sample showed excellent
      performance for the removal of crystal violet due to its high specific surface
      area and porous structures. Adsorption data fitted better with Langmuir isotherm
      and the maximum adsorption capacity was 2244.85 mg g(-1). The kinetic data was
      better described by pseudo-second order model and thermodynamic studies showed
      that adsorption process was spontaneous and endothermic. The adsorbent also
      showed very good reproducibility and reusability for the successive five cycles,
      indicating a promising potential material for environmental remediation.

PMID- 25985424
TI  - Surface chemistry and spectroscopy of the beta-galactosidase Langmuir monolayer.
AB  - The changes of interfacial properties of beta-galactosidase introduced into
      different pH environments are investigated through surface chemistry and in situ
      spectroscopy. Conditions for an optimal Langmuir monolayer formation were firstly
      obtained by varying the subphase salt concentration and the surface-pressure area
      isotherm was used to extrapolate the limiting molecular area of the enzyme
      monolayer to be around 42,000 A(2) molecule(-1). Surface pressure stability
      measurements held at 20 mN/m for 90 min along with compression-decompression
      cycles revealed no aggregate formation at the air-water interface. Consistent
      with the data obtained from the isotherm, in situ UV-Vis and fluorescence
      spectroscopy shows a steep rise in absorbance and photoluminescence intensity
      correlating to with a switch from a liquid-expanded to a liquid-condensed phase.
      A decrease in subphase pH increased the electrostatic repulsion as the enzyme was
      protonated, leading to an expanded monolayer. Infrared absorption-reflection
      spectroscopy demonstrates that the enzyme adopts mainly beta-sheet conformation
      at the air-water interface before and during the compression.

PMID- 25985425
TI  - Super-amphiphilic surface of nano silica/polyurethane hybrid coated PET film via
      a plasma treatment.
AB  - This study first reports the fabrication of a super-amphiphilic surface using PET
      films with a silica-polyurethane hybrid top-coat layer through a non-thermal, one
      atmospheric-pressure plasma treatment. This surface displays contact angle close
      to zero with both aqueous and oily liquids, which has attracted enormous
      attention for a wide-range of practical applications. We systematically
      investigated the influence of the plasma treatment time on the wetting behavior
      of the silica-polyurethane coated PET surface. The changes in morphology and
      chemical composition of PET surfaces before and after a plasma treatment were
      analyzed. In order to gain an insight into the formation of a super-amphiphilic
      PET surface and optimize the conditions under which super-amphiphilicity can be
      realized, we used a hemi-wicking action as a theoretical model and experimentally
      verified it through determining the critical angle. We also proposed a guide for
      designing a nano-sphere patterned PDMS surface which can generate super-wetting
      properties after a plasma treatment. 

PMID- 25985426
TI  - Motion and deformation of a droplet in a microfluidic cross-junction.
AB  - In this paper we investigate computationally the transient deformation of a
      droplet flowing along the centerline of a microfluidic cross-junction device. We
      consider naturally buoyant droplets with size smaller than the cross-section of
      the square channels comprising the cross-junction, and investigate low-to-strong
      flow rates and a wide range of fluids viscosity ratio. Our investigation shows
      that the intersecting flows at the cross-junction act like a constriction, and
      thus the droplet shows a rich deformation behavior as it passes through the micro
      junction. Our work highlights the three-dimensional effects of the asymmetric
      microfluidic geometry on the droplet deformation, and the different effects of
      the viscosity ratio on the droplet's overall length scales and the local length
      scales at the droplet edges. The large edge curvatures and thus the small local
      length scales developed transiently, especially at the tail of low-viscosity
      droplets, reveal that the current investigation is a multi-length interfacial
      dynamics problem. 

PMID- 25985427
TI  - Pressurized liquid extraction technique for the analysis of pesticides, PCBs,
      PBDEs, OPEs, PAHs, alkanes, hopanes, and steranes in atmospheric particulate
      matter.
AB  - An analytical method has been developed for the pressurized liquid extraction
      (PLE) of a wide range of semi-volatile organic compounds (SVOCs) from atmospheric
      particulate matter. Approximately 130 SVOCs from eight compound classes were
      selected as molecular markers of (1) agricultural activity (30 current and
      historic-use pesticides), (2) industrial activity (18 PCBs), (3) consumer
      products and building materials (16 PBDEs, 11 OPEs), and (4) motor vehicle
      exhaust (22 PAHs, 16 alkanes, 9 hopanes, 8 steranes). Currently, there is no
      analytical method validated for the extraction of all eight compound classes in a
      single automated technique. The extraction efficiencies of varying solvents and
      solvent combinations at high temperatures and pressures were examined. Extracts
      were concentrated and analyzed by gas chromatography coupled with mass
      spectrometry. The optimized PLE method utilized methylene chloride:acetone (2:1
      v/v) at 100  degrees C with three (5 min) static cycles, flush volume of 80%, and
      a 100 s N2 purge. Spike and recovery experiments (n=7) provided average percent
      recoveries for pesticides, PCBs, PBDEs, OPEs, PAHs, alkanes, hopanes, and
      steranes of 88.8+/-4.0%, 86.9+/-2.6%, 83.8+/-2.9%, 101+/-6%, 90.3+/-6.1%, 74.4+/
      8.8%, 104+/-8%, and 86.5+/-8.6%, respectively. The developed method was applied
      to atmospheric particulate matter samples collected in the greater Houston, TX
      metropolitan area. Ambient concentrations of eight classes of compounds (92
      SVOCs) were reported in pg m(-3).

PMID- 25985428
TI  - Current skin symptoms of Yusho patients exposed to high levels of 2,3,4,7,8
      pentachlorinated dibenzofuran and polychlorinated biphenyls in 1968.
AB  - Yusho was a mass food poisoning event due to the ingestion of rice oil
      contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin
      like compounds. At its outbreak in 1968, Yusho patients suffered severe skin
      symptoms. Although the blood concentrations of PCBs and dioxins, especially
      highly toxic 2,3,4,7,8-pentachlorinated dibenzofuran (2,3,4,7,8-PeCDF) remain
      high in these patients, extensive analysis has not been performed on their
      current skin symptoms. We categorized and evaluated the specific skin symptoms in
      Yusho in 2012 by grading their severity using an arbitrary scoring system, and
      analyzed their correlations with the blood concentrations of 2,3,4,7,8-PeCDF and
      PCBs. A total of 352 Yusho patients underwent annual dermatological check-ups, in
      which five skin symptoms: black comedones, acneiform eruptions, scar formation,
      pigmentation and nail deformity, were evaluated for their distribution and
      severity. Approximately one-third of Yusho patients still presented with black
      comedones, acneiform eruptions and scar formation; the distributions of these
      symptoms were similar to those at the time of the Yusho outbreak. The mean blood
      concentrations of 2,3,4,7,8-PeCDF and total PCBs in Yusho patients were still
      higher than those in controls. The prevalence and severity of black comedones
      were correlated with age. Severity scores of black comedones and scar formation
      were positively correlated with 2,3,4,7,8-PeCDF blood level, and those of black
      comedones, scar formation, and pigmentation were positively correlated with total
      PCBs blood level. This study suggests that 2,3,4,7,8-PeCDF and PCBs remaining in
      Yusho patients still play crucial roles in the development of skin symptoms in
      Yusho. 

PMID- 25985430
TI  - Retinal ganglion cell thickness to assess the optic nerve.

PMID- 25985429
TI  - Time to First Morning Cigarette and Risk of Chronic Obstructive Pulmonary
      Disease: Smokers in the PLCO Cancer Screening Trial.
AB  - BACKGROUND: Time to first cigarette (TTFC) after waking is an indicator of
      nicotine dependence. The association between TTFC and chronic obstructive
      pulmonary disease (COPD), the third leading cause of death in the United States,
      has not yet been reported. METHODS: We investigated the cross-sectional
      association between TTFC and prevalent COPD among 6,108 current smokers in the
      Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. COPD was
      defined as a self-reported diagnosis of emphysema, chronic bronchitis, or both.
      Current smokers in PLCO reported TTFC, the amount of time they typically waited
      before smoking their first cigarette of the day after waking, in four categories:
      <= 5, 6-30, 31-60, or > 60 minutes. We used logistic regression models to
      investigate the association between TTFC and prevalent COPD with adjustments for
      age, gender, race, education, and smoking (cigarettes/day, years smoked during
      lifetime, pack-years, age at smoking initiation), and prior lung cancer
      diagnosis. RESULTS: COPD was reported by 19% of these 6,108 smokers. Individuals
      with the shortest TTFC had the greatest risk of COPD; compared to those with the
      longest TTFC (> 60 minutes) the adjusted odds ratios (OR) and 95% confidence
      intervals (CI) for COPD were 1.48 (95% CI, 1.15-1.91), 1.64 (95% CI, 1.29-2.08),
      2.18 (95% CI, 1.65-2.87) for those with TTFC 31-60 minutes, 6-30 minutes, and <=
      5 minutes, respectively (P-trend < 0.0001). The association between TTFC and
      emphysema was similar to that for bronchitis, albeit the ORs were slightly
      stronger for chronic bronchitis; comparing TTFC <=5 minutes to > 60 minutes, the
      adjusted OR (95% CI) was 2.29 (1.69-3.12) for emphysema and 2.99 (1.95-4.59) for
      chronic bronchitis. CONCLUSIONS: Current smokers with shorter TTFC have increased
      risk of COPD compared to those with longer TTFC, even after comprehensive
      adjustment for established smoking covariates. Future epidemiologic studies,
      including prospective designs, should incorporate TTFC to better assess disease
      risk and evaluate the potential utility of TTFC as a COPD screening tool for
      smokers in the clinical setting.

PMID- 25985431
TI  - The intersection of optics and neuro-ophthalmology: the enigma of pseudophakic
      dysphotopsia.

PMID- 25985432
TI  - Superoxide generation explains common features of optic neuropathies associated
      with cecocentral scotomas.
AB  - I have presented above a hypothesis that ties together several disparate optic
      neuropathies, all characterized by a similar clinical presentation. The
      hypothesis is predicated on the formation of intracellular superoxide within RGCs
      as a common pathological pathway for the type of cell death that occurs. The
      anatomical predisposition of the papillomacular bundle to have elevated
      superoxide levels is tied to the size of the fibers involved, a hypothesis that
      also implicates the crossing fibers of the chiasm. Much of this work is
      speculative and is an interpretation of several experimental studies that have
      been performed to date. Hopefully, this hypothesis will be developed further, and
      its validity tested in both experimental models and, ultimately, in humans.

PMID- 25985433
TI  - Developing a human clinical trial from a scientific hypothesis.

PMID- 25985434
TI  - Vitamin D in multiple sclerosis and central nervous system demyelinating disease-
      a review.
AB  - BACKGROUND: The role of vitamin D as both a risk factor and a disease modifier in
      multiple sclerosis (MS) has a storied history with ongoing accumulation of
      supportive convergent evidence from animal data, clinical studies and trials, and
      biomarkers of disease. EVIDENCE ACQUISITION: A detailed review of the published
      literature ranging from in vivo immune studies to human clinical studies of
      epidemiology, physiology, immunology, clinical, and radiological markers was
      undertaken. RESULTS: There is compelling evidence that vitamin D is not only a
      risk factor for central nervous system (CNS) demyelinating disease (namely MS)
      but also seems to modify both the inflammatory and neurodegenerative elements of
      the disease, with large-scale treatment trials underway. The authors also address
      questions of interest that remain unanswered. CONCLUSIONS: Vitamin D is an
      important contributor and modifiable risk factor in CNS demyelinating disease.
      Further work will determine whether it is also neuroprotective and if such
      benefits will apply to other inflammatory and degenerative neurological diseases.

PMID- 25985435
TI  - Bilateral optic neuropathy after erythematous rash. Bilateral anterior optic
      neuropathy due to RMSF.

PMID- 25985436
TI  - Should Patients With Acute Central Retinal Artery Occlusion Be Treated With Intra
      arterial t-PA?

PMID- 25985437
TI  - Caesarean Section Frequency among Immigrants, Second- and Third-Generation Women,
      and Non-Immigrants: Prospective Study in Berlin/Germany.
AB  - OBJECTIVE: The frequency of caesarean section delivery varies between countries
      and social groups. Among other factors, it is determined by the quality of
      obstetrics care. Rates of elective (planned) and emergency (in-labor) caesareans
      may also vary between immigrants (first generation), their offspring (second- and
      third-generation women), and non-immigrants because of access and language
      barriers. Other important points to be considered are whether caesarean section
      indications and the neonatal outcomes differ in babies delivered by caesarean
      between immigrants, their offspring, and non-immigrants. METHODS: A standardized
      interview on admission to delivery wards at three Berlin obstetric hospitals was
      performed in a 12-month period in 2011/2012. Questions on socio-demographic and
      care aspects and on migration (immigrated herself vs. second- and third
      generation women vs. non-immigrant) and acculturation status were included. Data
      was linked with information from the expectant mothers' antenatal records and
      with perinatal data routinely documented in the hospital. Regression modeling was
      used to adjust for age, parity and socio-economic status. RESULTS: The caesarean
      section rates for immigrants, second- and third-generation women, and non
      immigrant women were similar. Neither indications for caesarean section delivery
      nor neonatal outcomes showed statistically significant differences. The only
      difference found was a somewhat higher rate of crash caesarean sections per 100
      births among first generation immigrants compared to non-immigrants. CONCLUSION:
      Unlike earlier German studies and current studies from other European countries,
      this study did not find an increased rate of caesarean sections among immigrants,
      as well as second- and third-generation women, with the possible exception of a
      small high-risk group. This indicates an equally high quality of perinatal care
      for women with and without a migration history.

PMID- 25985438
TI  - Tools to Promote Shared Decision Making in Serious Illness: A Systematic Review.
AB  - IMPORTANCE: Serious illness impairs function and threatens survival. Patients
      facing serious illness value shared decision making, yet few decision aids
      address the needs of this population. OBJECTIVE: To perform a systematic review
      of evidence about decision aids and other exportable tools that promote shared
      decision making in serious illness, thereby (1) identifying tools relevant to the
      treatment decisions of seriously ill patients and their caregivers, (2)
      evaluating the quality of evidence for these tools, and (3) summarizing their
      effect on outcomes and accessibility for clinicians. EVIDENCE REVIEW: We searched
      PubMed, CINAHL, and PsychInfo from January 1, 1995, through October 31, 2014, and
      identified additional studies from reference lists and other systematic reviews.
      Clinical trials with random or nonrandom controls were included if they tested
      print, video, or web-based tools for advance care planning (ACP) or decision aids
      for serious illness. We extracted data on the study population, design, results,
      and risk for bias using the Grading of Recommendations Assessment, Development,
      and Evaluation (GRADE) criteria. Each tool was evaluated for its effect on
      patient outcomes and accessibility. FINDINGS: Seventeen randomized clinical
      trials tested decision tools in serious illness. Nearly all the trials were of
      moderate or high quality and showed that decision tools improve patient knowledge
      and awareness of treatment choices. The available tools address ACP, palliative
      care and goals of care communication, feeding options in dementia, lung
      transplant in cystic fibrosis, and truth telling in terminal cancer. Five
      randomized clinical trials provided further evidence that decision tools improve
      ACP documentation, clinical decisions, and treatment received. CONCLUSIONS AND
      RELEVANCE: Clinicians can access and use evidence-based tools to engage seriously
      ill patients in shared decision making. This field of research is in an early
      stage; future research is needed to develop novel decision aids for other serious
      diagnoses and key decisions. Health care delivery organizations should prioritize
      the use of currently available tools that are evidence based and effective.

PMID- 25985439
TI  - Ab initio coordination chemistry for nickel chelation motifs.
AB  - Chelation therapy is one of the most appreciated methods in the treatment of
      metal induced disease predisposition. Coordination chemistry provides a way to
      understand metal association in biological structures. In this work we have
      implemented coordination chemistry to study nickel coordination due to its high
      impact in industrial usage and thereby health consequences. This paper reports
      the analysis of nickel coordination from a large dataset of nickel bound
      structures and sequences. Coordination patterns predicted from the structures are
      reported in terms of donors, chelate length, coordination number, chelate
      geometry, structural fold and architecture. The analysis revealed histidine as
      the most favored residue in nickel coordination. The most common chelates
      identified were histidine based namely HHH, HDH, HEH and HH spaced at specific
      intervals. Though a maximum coordination number of 8 was observed, the presence
      of a single protein donor was noted to be mandatory in nickel coordination. The
      coordination pattern did not reveal any specific fold, nevertheless we report
      preferable residue spacing for specific structural architecture. In contrast, the
      analysis of nickel binding proteins from bacterial and archeal species revealed
      no common coordination patterns. Nickel binding sequence motifs were noted to be
      organism specific and protein class specific. As a result we identified about 13
      signatures derived from 13 classes of nickel binding proteins. The specifications
      on nickel coordination presented in this paper will prove beneficial for
      developing better chelation strategies. 

PMID- 25985441
TI  - A single amino acid substitution in the mRNA capping enzyme lambda2 of a
      mammalian orthoreovirus mutant increases interferon sensitivity.
AB  - In the last few years, the development of a plasmid-based reverse genetics system
      for mammalian reovirus has allowed the production and characterization of mutant
      viruses. This could be especially significant in the optimization of reovirus
      strains for virotherapeutic applications, either as gene vectors or oncolytic
      viruses. The genome of a mutant virus exhibiting increased sensitivity to
      interferon was completely sequenced and compared with its parental virus. Viruses
      corresponding to either the parental or mutant viruses were then rescued by
      reverse genetics and shown to exhibit the expected phenotypes. Systematic rescue
      of different viruses harboring either of the four parental genes in a mutant
      virus backbone, or reciprocally, indicated that a single amino acid substitution
      in one of lambda2 methyltransferase domains is the major determinant of the
      difference in interferon sensitivity between these two viruses. 

PMID- 25985440
TI  - Ceramide formation mediated by acid sphingomyelinase facilitates endosomal escape
      of caliciviruses.
AB  - Our recent results demonstrated that bile acids facilitate virus escape from the
      endosomes into the cytoplasm for successful replication of porcine enteric
      calicivirus (PEC). We report a novel finding that bile acids can be substituted
      by cold treatment for endosomal escape and virus replication. This endosomal
      escape by cold treatment or bile acids is associated with ceramide formation by
      acid sphingomyelinase (ASM). ASM catalyzes hydrolysis of sphingomyelin into
      ceramide, which is known to destabilize lipid bilayer. Treatment of LLC-PK cells
      with bile acids or cold led to ceramide formation, and small molecule antagonists
      or siRNA of ASM blocked ceramide formation in the endosomes and significantly
      reduced PEC replication. Inhibition of ASM resulted in the retention of PEC,
      feline calicivirus or murine norovirus in the endosomes in correlation with
      reduced viral replication. These results suggest the importance of viral escape
      from the endosomes for the replication of various caliciviruses. 

PMID- 25985442
TI  - Transcranial direct current stimulation of the left dorsolateral prefrontal
      cortex shifts preference of moral judgments.
AB  - Attitude to morality, reflecting cultural norms and values, is considered unique
      to human social behavior. Resulting moral behavior in a social environment is
      controlled by a widespread neural network including the dorsolateral prefrontal
      cortex (DLPFC), which plays an important role in decision making. In the present
      study we investigate the influence of neurophysiological modulation of DLPFC
      reactivity by means of transcranial direct current stimulation (tDCS) on moral
      reasoning. For that purpose we administered anodal, cathodal, and sham
      stimulation of the left DLPFC while subjects judged the appropriateness of hard
      moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal
      stimulation induced a shift in judgment of personal moral dilemmas towards more
      non-utilitarian actions. Our results demonstrate that alterations of left DLPFC
      activity can change moral judgments and, in consequence, provide a causal link
      between left DLPFC activity and moral reasoning. Most important, the observed
      shift towards non-utilitarian actions suggests that moral decision making is not
      a permanent individual trait but can be manipulated; consequently individuals
      with boundless, uncontrollable, and maladaptive moral behavior, such as found in
      psychopathy, might benefit from neuromodulation-based approaches. 

PMID- 25985443
TI  - Advances in Muscular Dystrophies.

PMID- 25985444
TI  - Progress in the treatment of Ewing sarcoma: are the rumors of the demise of
      cytotoxic chemotherapy premature?
AB  - In this issue, Bollling et. al. review the development of treatment of Ewing
      sarcoma as it evolved over the past 30 years of clinical trials in Europe,
      largely under the leadership of Heribert Jurgens to whom this review is
      dedicated. The 44 authors were teachers, colleagues, students and co
      investigators of Jurgens. The authors attribute the ability to make progress in
      the treatment of Ewing sarcoma through the establishment of larger and still
      larger cooperative studies in order to demonstrate statistically significant
      advances in the treatment of this rare disease. 

PMID- 25985446
TI  - Randomised Introduction of 2-CDA as Intensification during Consolidation for
      Children with High-risk AML--results from Study AML-BFM 2004.
AB  - BACKGROUND: The outcome in children and adolescents with high-risk (HR) acute
      myeloid leukemia (AML) is still unsatisfactory. Therefore, in study AML-BFM 2004
      we aimed to improve outcome of HR-patients by adding moderately dosed 2-Chloro-2
      Deoxyadenosine (2-CDA) to the respective consolidation treatment backbone without
      increasing toxicity. The aim was to improve prognosis especially in FAB M4/M5/MLL
      patients, who represent the largest subgroup of HR patients. PATIENTS AND
      METHODS: In total, 343 children and adolescents with HR-AML were randomized to
      receive or not 2-CDA (6 mg/m2/d, days 1, 3) in combination with
      cytarabine/idarubicine (AI=500 mg/m2 cytarabine 5 days continuous infusion plus 7
      mg/m2/d idarubicin, days 3 and 5). RESULTS: RESULTS for patients of the AI/2-CDA
      arm (n=168) vs. the AI-arm (n=175) were similar: 5-year overall survival 68+/-4
      vs. 72+/-4%, plogrank=0.38, event-free survival 53+/-4 vs. 49+/-4%,
      plogrank=0.77; cumulative incidence of relapse at 5 years: 35+/-4 vs. 37+/-4%,
      p(Gray)=0.89. RESULTS in patients with MLL rearrangement or FAB M4/M5 were also
      similar in the treatment groups. In addition, toxicities did not differ between
      the two arms. CONCLUSION: We conclude that additional, moderate dose 2-CDA does
      not improve prognosis in HR-patients when given during consolidation treatment.
      Its effect might be too low in this multidrug regimen, where the strongest
      effects are achieved during induction, or the chosen dose of 2-CDA might have
      been too low.

PMID- 25985445
TI  - Development of curative therapies for Ewing sarcomas by interdisciplinary
      cooperative groups in Europe.
AB  - Curative therapies for Ewing sarcoma have been developed within cooperative
      groups. Consecutive clinical trials have systematically assessed the impact and
      timing of local therapy and the activity of cytotoxic drugs and their
      combinations. They have led to an increase of long-term disease-free survival to
      around 70% in patients with localized disease. Translational research in ES
      remains an area in which interdisciplinary and international cooperation is
      essential for future progress. This article reviews current state-of-the art
      therapy, with a focus on trials performed in Europe, and summarizes novel
      strategies to further advance both the cure rates and quality of survival. 

PMID- 25985447
TI  - Bortezomib Treatment can Overcome Glucocorticoid Resistance in Childhood B-cell
      Precursor Acute Lymphoblastic Leukemia Cell Lines.
AB  - BACKGROUND: The response to initial glucocorticoid (gc) treatment is a reliable
      stratification factor in childhood acute lymphoblastic leukemia (ALL) and may
      predict the response to multi-agent chemotherapy. In a former study we detected
      that the valosin-containing protein (VCP, cdc48), a member of the ubiquitin
      proteasome degradation system (UPS), is altered in gc-resistant leukemic cells
      suggesting that the associated pathways might be involved in chemotherapy
      resistance in childhood ALL. METHODS: Human B-cell precursor leukemia cell lines,
      gc-resistant MHH-cALL-2 and gc-sensitive MHH-cALL-3, were treated with
      prednisolone and various concentrations of bortezomib. Viability and apoptosis
      rates were determined. RESULTS: Both cell lines showed a dose-dependent increase
      in caspase activity after bortezomib single treatment. The gc-sensitive cells
      showed an additive effect after combined treatment with prednisolone and
      bortezomib. In contrast, both cell lines showed a reduced viability and enhanced
      propidium iodide positivity after combined treatment as determined by flow
      cytometry. Western blot analyses of poly-(ADP-ribose) polymerase 1 (PARP-1)
      suggested that combined treatment promote necrotic cleavage of PARP-1 in gc
      resistant cells. Furthermore, after prednisolone treatment the UPS associated
      proteins VCP and NFkappaB-inhibitor IkappaBalpha were differentially modulated in
      gc-resistant cells. CONCLUSIONS: The proteasome inhibitor bortezomib seems to
      sensitize gc-resistant childhood ALL cells for prednisolone-induced cell death.

PMID- 25985448
TI  - Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls
      Experienced in the THROMKID Quality Project.
AB  - BACKGROUND: Primary haemostasis defects comprise von Willebrand disease (VWD) and
      platelet disorders (PD). Although presenting with mild to moderate bleeding
      tendency in most cases, severe bleeding and blood loss may occur unexpectedly in
      trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the
      wide spectrum of clinical and laboratory manifestations. Platelet-type von
      Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD.
      Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs.
      METHODS AND RESULTS: A literature review revealed difficulties in diagnostic work
      up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic
      use of platelet concentrates. A telephone survey of diagnostic practice with
      regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type
      2B and PT-VWD remained unclear, but PT-VWD may be underestimated. DISCUSSION: An
      international study estimated that PT-VWD constitutes up to 15% of the total
      number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties
      with diagnosis and showed that some centres did not exclude PT-VWD in type 2B
      patients. Some authors emphasize that genetic testing is the gold standard for
      diagnosis, but functional testing allows immediate diagnosis. Due to the
      important therapeutic implications we suggest that type 2B VWD be confirmed by
      genetic testing and that in case of a negative result PT-VWD should be excluded.
      CONCLUSION: PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD
      should be treated with platelet concentrates.

PMID- 25985449
TI  - Consensus of German transplant centers on hematopoietic stem cell transplantation
      in Fanconi anemia.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only
      curative therapy for the severe hematopoietic complications associated with
      Fanconi anemia (FA). In Germany, it is estimated that 10-15 transplants are
      performed annually for FA. However, because FA is a DNA repair disorder, standard
      conditioning regimens confer a high risk of excessive regimen-related toxicities
      and mortality, and reduced intensity regimens are linked with graft failure in
      some FA patients. Moreover, development of graft-versus-host disease is a major
      contributing factor for secondary solid tumors. The relative rarity of the
      disorder limits HSCT experience at any single center. Consensus meetings were
      convened to develop a national approach for HSCT in FA. This manuscript outlines
      current experience and knowledge about HSCT in FA and, based on this analysis,
      general recommendations reached at these meetings. 

PMID- 25985450
TI  - Design, implementation, and evaluation of a mobile application for patient
      empowerment and management of long-term follow-up after childhood cancer.
AB  - In Germany, about 1,800 new cases of childhood cancer are diagnosed every year.
      The chances of survival have increased significantly over the last 40 years due
      to the continuous improvement of treatment strategies. The number of childhood
      cancer survivors in Germany thus ranges around 30,000 nowadays. But their
      treatment with surgery, chemotherapy, and radiation has certain side-effects. In
      addition to the acute effects during the treatment phase, the disease- and
      treatment-related late effects can occur even decades after the end of therapy.
      These late effects draw attention as the survival rate constantly increases. Two
      thirds of the former patients retain long-term consequences, nearly a fifth with
      a resulting diminished quality of life. Early detection of these late effects can
      help to reduce or even to prevent serious health damage. Therefore, the study
      group LESS supplies long-term follow-up recommendations for former patients. The
      project described in this paper was to design and implement a mobile application
      to increase the compliance for this aftercare program. This application provides
      information about the patient's individual aftercare plan and supports
      appointment management as well as a reminding functionality. A prototype for
      former osteosarcoma patients was tested and evaluated in two university
      hospitals. First results show the application's very high potential for patient
      empowerment.

PMID- 25985451
TI  - Delayed Diagnosis of Platelet-type von Willebrand Disease in a 72-year-old Lady.

PMID- 25985452
TI  - Eosinophilic esophagitis as paraneoplastic syndrome in a patient with
      ganglioneuroblastoma.
AB  - A 16-month-old boy presented with failure to thrive despite sufficient caloric
      intake, hypersalivation, abdominal pain, chronic diarrhea and blepharitis. An
      eosinophilic esophagitis (EoE) was diagnosed by esophageal biopsy. Dietary
      restrictions and topical steroid treatment lead to no improvement. Further
      diagnostic work-up revealed an intrathoracal, paraspinal ganglioneuroblastoma.
      After operative extirpation of the tumour, all initial symptoms resolved. An
      esophageal control biopsy 4 weeks after tumour resection was normal. This is the
      first report of eosinophilic esophagitis as part of a paraneoplastic syndrome in
      a patient with a malignant disease other than a carcinoma. 

PMID- 25985453
TI  - [Vascular anomaly in the midcheek region of an infant--review of the diagnostic
      procedure].
AB  - Clinical history, physical examination, evolution and imaging findings (Colour
      Doppler sonography, MRI if available) are of pivotal importance in the diagnostic
      pathway of an infantile vascular anomaly. Histopathology with specific stains and
      markers is contributive in difficult cases. Differentiation between vascular
      tumors (hemangioma) and vascular malformations is now well known and integrated
      into the ISSVA classification. We report here a 6-months-old boy, who presented
      with a localized cutaneous and expansive vascular birthmark in the left cheek and
      developed bleedings at the age of 18 months. Diagnostic features of a hemangioma
      were not evident, and the final diagnosis of a venous malformation was confirmed
      by histopathology. 

PMID- 25985454
TI  - A Field Study on the Respiratory Deposition of the Nano-Sized Fraction of Mild
      and Stainless Steel Welding Fume Metals.
AB  - A field study was conducted to estimate the amount of Cr, Mn, and Ni deposited in
      the respiratory system of 44 welders in two facilities. Each worker wore a
      nanoparticle respiratory deposition (NRD) sampler during gas metal arc welding
      (GMAW) of mild and stainless steel and flux-cored arc welding (FCAW) of mild
      steel. Several welders also wore side-by-side NRD samplers and closed-face filter
      cassettes for total particulate samples. The NRD sampler estimates the aerosol's
      nano-fraction deposited in the respiratory system. Mn concentrations for both
      welding processes ranged 2.8-199 MUg/m3; Ni concentrations ranged 10-51 MUg/m3;
      and Cr concentrations ranged 40-105 MUg/m3. Cr(VI) concentrations ranged between
      0.5-1.3 MUg/m3. For the FCAW process the largest concentrations were reported for
      welders working in pairs. As a consequence this often resulted in workers being
      exposed to their own welding fumes and to those generated from the welding
      partner. Overall no correlation was found between air velocity and exposure (R2 =
      0.002). The estimated percentage of the nano-fraction of Mn deposited in a mild
      steel-welder's respiratory system ranged between 10 and 56%. For stainless steel
      welding, the NRD samplers collected 59% of the total Mn, 90% of the total Cr, and
      64% of the total Ni. These results indicate that most of the Cr and more than
      half of the Ni and Mn in the fumes were in the fraction smaller than 300 nm.

PMID- 25985455
TI  - Implanted materials: Larger is stealthier.

PMID- 25985457
TI  - Measuring surface dislocation nucleation in defect-scarce nanostructures.
AB  - Linear defects in crystalline materials, known as dislocations, are central to
      the understanding of plastic deformation and mechanical strength, as well as
      control of performance in a variety of electronic and photonic materials. Despite
      nearly a century of research on dislocation structure and interactions,
      measurements of the energetics and kinetics of dislocation nucleation have not
      been possible, as synthesizing and testing pristine crystals absent of defects
      has been prohibitively challenging. Here, we report experiments that directly
      measure the surface dislocation nucleation strengths in high-quality <110> Pd
      nanowhiskers subjected to uniaxial tension. We find that, whereas nucleation
      strengths are weakly size- and strain-rate-dependent, a strong temperature
      dependence is uncovered, corroborating predictions that nucleation is assisted by
      thermal fluctuations. We measure atomic-scale activation volumes, which explain
      both the ultrahigh athermal strength as well as the temperature-dependent
      scatter, evident in our experiments and well captured by a thermal activation
      model. 

PMID- 25985456
TI  - Size- and shape-dependent foreign body immune response to materials implanted in
      rodents and non-human primates.
AB  - The efficacy of implanted biomedical devices is often compromised by host
      recognition and subsequent foreign body responses. Here, we demonstrate the role
      of the geometry of implanted materials on their biocompatibility in vivo. In
      rodent and non-human primate animal models, implanted spheres 1.5 mm and above in
      diameter across a broad spectrum of materials, including hydrogels, ceramics,
      metals and plastics, significantly abrogated foreign body reactions and fibrosis
      when compared with smaller spheres. We also show that for encapsulated rat
      pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6
      mice, islets prepared in 1.5-mm alginate capsules were able to restore blood
      glucose control for up to 180 days, a period more than five times longer than for
      transplanted grafts encapsulated within conventionally sized 0.5-mm alginate
      capsules. Our findings suggest that the in vivo biocompatibility of biomedical
      devices can be significantly improved simply by tuning their spherical
      dimensions. 

PMID- 25985458
TI  - Conformal piezoelectric systems for clinical and experimental characterization of
      soft tissue biomechanics.
AB  - Mechanical assessment of soft biological tissues and organs has broad relevance
      in clinical diagnosis and treatment of disease. Existing characterization methods
      are invasive, lack microscale spatial resolution, and are tailored only for
      specific regions of the body under quasi-static conditions. Here, we develop
      conformal and piezoelectric devices that enable in vivo measurements of soft
      tissue viscoelasticity in the near-surface regions of the epidermis. These
      systems achieve conformal contact with the underlying complex topography and
      texture of the targeted skin, as well as other organ surfaces, under both quasi
      static and dynamic conditions. Experimental and theoretical characterization of
      the responses of piezoelectric actuator-sensor pairs laminated on a variety of
      soft biological tissues and organ systems in animal models provide information on
      the operation of the devices. Studies on human subjects establish the clinical
      significance of these devices for rapid and non-invasive characterization of skin
      mechanical properties. 

PMID- 25985459
TI  - Quasiparticle-mediated spin Hall effect in a superconductor.
AB  - In some materials the competition between superconductivity and magnetism brings
      about a variety of unique phenomena such as the coexistence of superconductivity
      and magnetism in heavy-fermion superconductors or spin-triplet supercurrent in
      ferromagnetic Josephson junctions. Recent observations of spin-charge separation
      in a lateral spin valve with a superconductor evidence that these remarkable
      properties are applicable to spintronics, although there are still few works
      exploring this possibility. Here, we report the experimental observation of the
      quasiparticle-mediated spin Hall effect in a superconductor, NbN. This compound
      exhibits the inverse spin Hall (ISH) effect even below the superconducting
      transition temperature. Surprisingly, the ISH signal increases by more than 2,000
      times compared with that in the normal state with a decrease of the injected spin
      current. The effect disappears when the distance between the voltage probes
      becomes larger than the charge imbalance length, corroborating that the huge ISH
      signals measured are mediated by quasiparticles. 

PMID- 25985461
TI  - Cervical radiculopathy: epidemiology, etiology, diagnosis, and treatment.
AB  - Cervical radiculopathy is a relatively common neurological disorder resulting
      from nerve root dysfunction, which is often due to mechanical compression;
      however, inflammatory cytokines released from damaged intervertebral disks can
      also result in symptoms. Cervical radiculopathy can often be diagnosed with a
      thorough history and physical examination, but an magnetic resonance imaging or
      computed tomographic myelogram should be used to confirm the diagnosis. Because
      of the ubiquity of degenerative changes found on these imaging modalities, the
      patient's symptoms must correlate with pathology for a successful diagnosis. In
      the absence of myelopathy or significant muscle weakness all patients should be
      treated conservatively for at least 6 weeks. Conservative treatments consist of
      immobilization, anti-inflammatory medications, physical therapy, cervical
      traction, and epidural steroid injections. Cervical radiculopathy typically is
      self-limiting with 75%-90% of patients achieving symptomatic improvement with
      nonoperative care. For patients who are persistently symptomatic despite
      conservative treatment, or those who have a significant functional deficit
      surgical treatment is appropriate. Surgical options include anterior cervical
      decompression and fusion, cervical disk arthroplasty, and posterior foraminotomy.
      Patient selection is critical to optimize outcome. 

PMID- 25985460
TI  - Olive Volatiles from Portuguese Cultivars Cobrancosa, Madural and Verdeal
      Transmontana: Role in Oviposition Preference of Bactrocera oleae (Rossi)
      (Diptera: Tephritidae).
AB  - The olive fly, Bactrocera oleae (Rossi), a serious threat to the olive crop
      worldwide, displays ovipositon preference for some olive cultivars but the causes
      are still unclear. In the present work, three Portuguese olive cultivars with
      different susceptibilities to olive fly (Cobrancosa, Madural, and Verdeal
      Transmontana) were studied, aiming to determine if the olive volatiles are
      implicated in this interaction. Olive volatiles were assessed by SPME-GC-MS in
      the three cultivars during maturation process to observe possible correlations
      with olive fly infestation levels. Overall, 34 volatiles were identified in the
      olives, from 7 chemical classes (alcohols, aldehydes, aromatic hydrocarbons,
      esters, ketones, sesquiterpenes, and terpenes). Generally, total volatile amounts
      decrease during maturation but toluene, the main compound, increased in all
      cultivars, particularly in those with higher susceptibility to olive fly.
      Sesquiterpenes also raised, mainly alpha-copaene. Toluene and alpha-copaene,
      recognized oviposition promoters to olive fly, were correlated with the
      infestation level of cvs. Madural and Verdeal Trasnmontana (intermediate and
      highly susceptible cultivars respectively), while no correlations were
      established with cv. Cobrancosa (less susceptible). No volatiles with inverse
      correlation were observed. Volatile composition of olives may be a decisive
      factor in the olive fly choice to oviposit and this could be the basis for the
      development of new control strategies for this pest. 

PMID- 25985462
TI  - Do you need bone graft extenders for a 2- to 3-level posterior lumbar
      decompression and fusion with adequate local bone?

PMID- 25985463
TI  - Inflection Points in Magnetic Resonance Imaging Technology-35 Years of
      Collaborative Research and Development.
AB  - The technology for clinical magnetic resonance imaging (MRI) has advanced with
      remarkable speed and in such a manner reflecting the influence of 3 forces
      collaboration between disciplines, collaboration between academia and industry,
      and the enabling of software applications by hardware. The forces are evident in
      the key developments from the past and emerging trends for the future highlighted
      in this review article. These developments are associated with MRI system
      attributes, such as wider, shorter, and stronger magnets; specialty magnets and
      hybrid devices; k space; and the notion that magnetic field gradients perform a
      Fourier transform on the spatial distribution of magnetization, phased-array
      coils and parallel imaging, the user interface, the wide range of contrast
      possible, and applications that exploit motion-induced phase shifts. An attempt
      is made to show connections between these developments and how the 3 forces
      mentioned previously will continue to shape the technology used so productively
      in clinical MRI. 

PMID- 25985464
TI  - Cardiovascular Imaging: The Past and the Future, Perspectives in Computed
      Tomography and Magnetic Resonance Imaging.
AB  - Today's noninvasive imaging of the cardiovascular system has revolutionized the
      approach to various diseases and has substantially affected prognostic
      information. Cardiovascular magnetic resonance (MR) and computed tomographic (CT)
      imaging are at center stage of these approaches, although 5 decades ago, these
      technologies were unheard of. Both modalities had their inception in the 1970s
      with a primary focus on noncardiovascular applications. The technical development
      of the various decades, however, substantially pushed the envelope for
      cardiovascular MR and CT applications. Within the past 10-15 years, MR and CT
      technologies have pushed each other in cardiac applications; and without the
      "rival" modality, neither one would likely not have reached its potential today.
      This view on the history of MR and CT in the field of cardiovascular applications
      provides insight into the story of success of applications that once have been
      ideas only but are at prime time today. 

PMID- 25985465
TI  - Two-dimensional wavelike spinel lithium titanate for fast lithium storage.
AB  - Safe fast-charging lithium-ion batteries (LIBs) have huge potential market size
      on demand according to their shortened charging time for high-power devices. Zero
      strain spinel Li4Ti5O12 is one of ideal candidates for safe high-power batteries
      owing to its good cycling performance, low cost and safety. However, the inherent
      insulating characteristic of LTO seriously limits its high-rate capability. In
      this work, we successfully synthesize novel wavelike spinel LTO nanosheets using
      a facile 'co-hydrolysis' method, which is superior to molten-salt approach and
      traditional solvothermal method in some respects. The unique 2D structures have
      single-crystal framework with shortened path for Li ion transport. As a result,
      the N-doped 2D wavelike LTO with 0.6 wt.% of 'carbon joint' not only exhibits
      exciting capacity of ~180 and ~150 mA h g(-1) for fast lithium storage at high
      discharge/charge rates of 1.7 and 8.5 A g(-1) (10C and 50C) respectively, but
      also shows excellent low-temperature performance at -20 degrees C. In addition,
      the cost may be further decreased due to recycled functional reagents. This novel
      nanostructured 2D LTO anode material makes it possible to develop safe fast
      charging high-power lithium ion batteries.

PMID- 25985467
TI  - Educational apps: what we do and do not know.

PMID- 25985468
TI  - Putting education in "educational" apps: lessons from the science of learning.
AB  - Children are in the midst of a vast, unplanned experiment, surrounded by digital
      technologies that were not available but 5 years ago. At the apex of this boom is
      the introduction of applications ("apps") for tablets and smartphones. However,
      there is simply not the time, money, or resources available to evaluate each app
      as it enters the market. Thus, "educational" apps-the number of which, as of
      January 2015, stood at 80,000 in Apple's App Store (Apple, 2015)-are largely
      unregulated and untested. This article offers a way to define the potential
      educational impact of current and future apps. We build upon decades of work on
      the Science of Learning, which has examined how children learn best. From this
      work, we abstract a set of principles for two ultimate goals. First, we aim to
      guide researchers, educators, and designers in evidence-based app development.
      Second, by creating an evidence-based guide, we hope to set a new standard for
      evaluating and selecting the most effective existing children's apps. In short,
      we will show how the design and use of educational apps aligns with known
      processes of children's learning and development and offer a framework that can
      be used by parents and designers alike. Apps designed to promote active, engaged,
      meaningful, and socially interactive learning-four "pillars" of learning-within
      the context of a supported learning goal are considered educational.

PMID- 25985470
TI  - The Effect of Physical Exercise on Postural Stability in Sighted   Individuals
      and Those Who Are Visually Impaired: An Analysis   Adjusted for Physical Activity
      and Body Mass Index.
AB  - The aim of this study was to assess the effect of physical exercise on postural
      stability in sighted participants and individuals who are visually impaired,
      adjusted for potential modulatory effects of physical activity level and body
      mass index (BMI). The study included 23 participants who were severely visually
      impaired and 23 sighted participants. Postural stability measurements were taken
      with open eyes (session I) and with closed eyes (session II). During each
      session, the mean velocity of the center of pressure (COP) displacements was
      determined using a force plate both before and after physical exercise. During
      testing with open eyes, the 2 groups did not differ significantly in terms of
      their postural response to physical exercise. When examined with closed eyes, the
      individuals who were visually impaired showed markedly greater postexercise
      increase in mean velocity of the COP displacement in the mediolateral direction.
      This intergroup difference was likely a consequence of significantly higher
      preexercise values of posturographic parameters observed in the sighted
      participants. More pronounced postexercise changes in the postural stability of
      sighted participants were associated with lower levels of physical activity and
      higher values of BMI. Further research is needed to explain the character of the
      abovementioned relationships in individuals who are visually impaired.

PMID- 25985471
TI  - Descriptive Epidemiology of Physical Activity Levels and Patterns in New
      Zealanders in Advanced Age.
AB  - BACKGROUND: Little is known about the physical activity levels and behaviors of
      advanced age New Zealanders. METHODS: A cross-sectional analysis of data from
      Life and Living in Advanced Age: A Cohort Study in New Zealand (LiLACS NZ), Te
      Puawaitanga O Nga Tapuwae Kia ora Tonu, measures of physical activity (PASE) (n =
      664, aged 80-90 [n = 254, Maori, aged 82.5(2), n = 410 non-Maori, aged 85(.5)])
      was conducted to determine physical activity level (PAL). A substudy (n = 45) was
      conducted to attain detailed information about PAL and behaviors via the
      Multimedia Activity Recall for Children and Adults (MARCA) and accelerometry. The
      main study was analyzed by sex for Maori and non-Maori. RESULTS: Men consistently
      had higher levels of physical activity than women for all physical activity
      measures. Sex was significant for different domains of activity.

PMID- 25985473
TI  - Ethics and the practice of anesthesia.

PMID- 25985472
TI  - Increasing the Availability of Physical Activity Programs for Older Adults:
      Lessons Learned From Texercise Stakeholders.
AB  - Many initiatives have been developed to facilitate older adults' engagement in
      physical activity (PA) and document its benefits. One example is Texercise, a 12
      week program with a focus on increasing participants' self-efficacy. The goal of
      this paper is to augment the knowledgebase of PA program implementation and
      dissemination by elucidating the experience of Texercise implementation as
      perceived by multiple stakeholders. We conducted 28 semistructured stakeholder
      interviews and categorized the responses into four preset themes: (1) program
      delivery and advocacy; (2) value/merit of the program; (3) successes/challenges
      of offering and sustaining the program; and (4) recommendations for enhancing
      implementation and delivery. We identified emergent subthemes through further
      analysis. Many perceptions that are broadly applicable to community organizations
      emerged. Our findings highlight the importance of stakeholder support when
      embedding PA programs in communities. Furthermore, the findings are crucial to
      understanding underlying processes that support widespread program dissemination
      and sustainability. 

PMID- 25985474
TI  - [Abstracts of the 13th Congress of the French Society of Vascular Medicine, 2014,
      Montpellier, France].

PMID- 25985475
TI  - Anesthesiology's contributions to medicine.

PMID- 25985476
TI  - Driving distance eligibility for the Veterans Choice Program. Interim final rule.
AB  - The Department of Veterans Affairs (VA) amends its medical regulations
      implementing section 101 of the Veterans Access, Choice, and Accountability Act
      of 2014, which directed VA to establish a program to furnish hospital care and
      medical services through eligible non-VA health care providers to eligible
      veterans who either cannot be seen within the wait-time goals of the Veterans
      Health Administration or who qualify based on their place of residence (hereafter
      referred to as the Veterans Choice Program, or the "Program''). VA published an
      interim final rule implementing the Veterans Choice Program on November 5, 2014.
      Under current law, VA uses a straight-line or geodesic distance to determine
      eligibility based on place of residence. This interim final rule modifies how VA
      measures the distance from a veteran's residence to the nearest VA medical
      facility. This modified standard will consider the distance the veteran must
      drive to the nearest VA medical facility, rather than the straight-line or
      geodesic distance to such a facility.

PMID- 25985477
TI  - Health Care for Homeless Veterans program. Final rule.
AB  - The Department of Veterans Affairs (VA) amends its medical regulations concerning
      eligibility for the Health Care for Homeless Veterans (HCHV) program. The HCHV
      program provides per diem payments to non-VA community-based facilities that
      provide housing, outreach services, case management services, and rehabilitative
      services, and may provide care and/or treatment to homeless veterans who are
      enrolled in or eligible for VA health care. The rule modifies VA's HCHV
      regulations to conform to changes enacted in the Honoring America's Veterans and
      Caring for Camp Lejeune Families Act of 2012. Specifically, the rule removes the
      requirement that homeless veterans be diagnosed with a serious mental illness or
      substance use disorder to qualify for the HCHV program. This change makes the
      program available to all homeless veterans who are enrolled in or eligible for VA
      health care. The rule also updates the definition of homeless to match in part
      the one used by the Department of Housing and Urban Development (HUD). The rule
      further clarifies that the services provided by the HCHV program through non-VA
      community-based providers must include case management services, including non
      clinical case management, as appropriate.

PMID- 25985478
TI  - Medical devices; physical medicine devices; classification of the powered lower
      extremity exoskeleton; republication. Final order; republication.
AB  - The Food and Drug Administration (FDA or the Agency) is republishing in its
      entirety a final order entitled ''Medical Devices; Physical Medicine Devices;
      Classification of the Powered Lower Extremity Exoskeleton'' that published in the
      Federal Register on February 24, 2015. FDA is republishing to correct an
      inadvertent omission of information. FDA is classifying the powered lower
      extremity exoskeleton into class II (special controls). The special controls that
      will apply to the device are identified in this order and will be part of the
      codified language for the powered lower extremity exoskeleton's classification.
      The Agency is classifying the device into class II (special controls) in order to
      provide a reasonable assurance of safety and effectiveness of the device.

PMID- 25985479
TI  - Grants for adaptive sports programs for disabled veterans and disabled members of
      the Armed Forces. Final rule.
AB  - This final rule amends Department of Veterans Affairs (VA) regulations to
      establish a new program to provide grants to eligible entities to provide
      adaptive sports activities to disabled veterans and disabled members of the Armed
      Forces. This rulemaking is necessary to implement a change in the law that
      authorizes VA to make grants to entities other than the United States Olympic
      Committee for adaptive sports programs. It establishes procedures for evaluating
      grant applications under this grant program, and otherwise administering the
      grant program. This rule implements section 5 of the VA Expiring Authorities
      Extension Act of 2013.

PMID- 25985480
TI  - Medicare program; changes to the requirements for Part D prescribers. Interim
      final rule with comment period.
AB  - This interim final rule with comment period revises requirements related to
      beneficiary access to covered Part D drugs. Under these revised requirements,
      pharmacy claims and beneficiary requests for reimbursement for Medicare Part D
      prescriptions, written by prescribers other than physicians and eligible
      professionals who are permitted by state or other applicable law to prescribe
      medications, will not be rejected at the point of sale or denied by the plan if
      all other requirements are met. In addition, a plan sponsor will not reject a
      claim or deny a beneficiary request for reimbursement for a drug when prescribed
      by a prescriber who does not meet the applicable enrollment or opt-out
      requirement without first providing provisional coverage of the drug and
      individualized written notice to the beneficiary. This interim final rule with
      comment period also revises certain terminology to be consistent with existing
      policy and to improve clarity.

PMID- 25985481
TI  - Organ procurement and transplantation: implementation of the HIV Organ Policy
      Equity Act. Final rule.
AB  - This final rule amends the regulations implementing the National Organ Transplant
      Act of 1984, as amended, (NOTA) pursuant to statutory requirements of the HIV
      Organ Policy Equity Act (HOPE Act), enacted in 2013. In accordance with the
      mandates of the HOPE Act, this regulation removes the current regulatory
      provision that requires the Organ Procurement Transplantation Network (OPTN) to
      adopt and use standards for preventing the acquisition of organs from individuals
      known to be infected with human immunodeficiency virus (HIV). In its place, this
      regulation includes new requirements that organs from individuals infected with
      HIV may be transplanted only into individuals who are infected with HIV before
      receiving such organs and who are participating in clinical research approved by
      an institutional review board, as provided by regulation. The only exception to
      this requirement of participation in such clinical research is if the Secretary
      publishes a determination in the future that participation in such clinical
      research, as a requirement for transplants of organs from individuals infected
      with HIV, is no longer warranted. In addition, this regulatory change establishes
      that OPTN standards must ensure that any HIV-infected transplant recipients are
      participating in clinical research in accordance with the research criteria to be
      published by the Secretary. Alternately, if and when the Secretary determines
      that participation in such clinical research should no longer be a requirement
      for transplants with organs from donors infected with HIV to individuals infected
      with HIV, the regulation mandates that the OPTN adopt and use standards of
      quality, as directed by the Secretary, consistent with the law and in a way that
      ensures the changes will not reduce the safety of organ transplantation.

PMID- 25985482
TI  - Schedules of controlled substances: extension of temporary placement of UR-144,
      XLR11, and AKB48 in schedule I of the Controlled Substances Act. Final order.
AB  - The Administrator of the Drug Enforcement Administration (DEA) is issuing this
      final order to extend the temporary placement of (1-pentyl-1H-indol-3-yl)(2,2,3,3
      tetramethylcyclopropyl)methanone (UR-144), [1-(5-fluoro-pentyl)-1H-indol-3
      yl](2,2,3,3-tetramethylcyclopropyl)methanone (5-fluoro-UR-144, XLR11) and N-(1
      adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA, AKB48), including their
      salts, isomers, and salts of isomers whenever the existence of such salts,
      isomers, and salts of isomers is possible, in schedule I of the Controlled
      Substances Act. The current final order temporarily placing UR-144, XLR11, and
      AKB48 in schedule I is due to expire on May 15, 2015. This final order will
      extend the temporary scheduling of UR-144, XLR11, and AKB48 to May 15, 2016, or
      until the permanent scheduling action for these three substances is completed,
      whichever occurs first.

PMID- 25985483
TI  - [Mindfulness-based cognitive therapy].

PMID- 25985484
TI  - [CO2-exchange in tundra ecosystems of Vaygach Island during the unusually warm
      and dry vegetation season].
AB  - In summer of 2013, field studies of CO2-exchange in tundra ecosystems of Vaygach
      Island have been conducted using the chamber method. The models are developed
      that establish relationships between CO2 fluxes and key ecological factors such
      as temperature, photosynthetic active radiation, leaf mass of vascular plants,
      and depth of thawing. According to the model estimates, in 2013 vegetation season
      tundra ecosystems of Vaygach Island have been appearing to be a CO2 source to the
      atmosphere (31.9 +/- 17.1 g C m(-2) season(-1)) with gross primary production
      equal to 136.6 +/- 18.9 g C m(-2) season(-1) and ecosystem respiration of 168.5
      +/- +/- 18.4 g C m(-2) season(-1). Emission of CO2 from the soil surface (soil
      respiration) has been equal, on the average, to 67.3% of the ecosystem
      respiration. The reason behind carbon losses by tundra ecosystems seems to be
      unusually warm and dry weather conditions in 2013 summer. The air temperature
      during summer months has been twice as high as the climatic norm for 1961-1990.
      Last decades, researches in the circumpolar Arctic revealed a growing trend to
      the carbon sink from the atmosphere to tundra ecosystems. This trend can be
      interrupted by unusually warm weather situations becoming more frequent and of
      larger scale.

PMID- 25985485
TI  - [The fate of subspecies category in zoological systematics. 2. The present].
AB  - The present approach to the use of subspecies category in zoological systematics
      is an integrative one. It counts as obligatory to confirm the validity of
      subspecies, defined by morphological data, with genetic criteria. This allows
      marking out those subspecies that really exist as separate monophyletic
      population groups. As a result, the system would be cleared of many 'phantom'
      taxa established in course of non-critical use of the subspecies concept.
      However, detailed analyses of intra-species variability by methods of molecular
      taxonomy in many cases reveal a quite complicated divergence pattern which cannot
      be adequately described in terms of the classic scheme of 'species and its
      subspecies'. Keeping in mind the irregularity of intra-species divergence rate
      when dealing with molecular and morphological traits, it is proposed to use an
      extended system of subspecies taxa when describing 'extra complicated'
      situations. In addition to a 'subspecies' such categories as 'allospecies',
      'morphotype', 'morphospecies' may be used for which operational definitions are
      suggested. As an example, the micro-systematics of the great pond snails (the
      complex Lymnaea stagnalis s. lato) from Palaearctic region is examined. The
      provisional system of this group, developed by the author, is based on
      morphological and phylogeographical data. Applying the series of subspecies
      categories of different level allows reflecting with maximal completeness the
      intra-species variability of great pond snails and, to some extent, the process
      of their genetic divergence and geographic range forming. The second part of the
      article deals with modern approaches to subspecies category usage in zoological
      systematics as well as the problems of so called micro-systematics, i.e.,
      systematics operating at the lowest level of categories such as ones of
      subspecies and infra-subspecies rank (Mayr, 1982).

PMID- 25985486
TI  - [Assessing the relative strength of the effects of food resources and predators
      on a population: a review of methods].
AB  - Understanding mechanisms that underlie species' distribution and abundance is one
      of the key problems in population ecology. Inorder to tackle this problem, it is
      important to assess the relative strength of the effects of food and predator
      (consumer) on a focal population. In this study we have analysed advantages and
      disadvantages of the basic methods that are used to quantify the relative
      strength of the two types of effects. These methods can be divided into two
      groups. In the first group we put the search for examples that are consistent
      with a proposed hypothesis, assessment of correlations of abundance on adjacent
      trophic levels and biomanipulations. Common for these methods is that they assume
      the existence of only one type of effects--either bottom-up or top-down. Methods
      of the second group assume simultaneous presence of both types of effects and are
      aimed at quantifying their relative strength. In this group we put factorial
      design experiments and population-dynamics approach (analysis of population
      growth, death and birth rates). It is shown that due to the constraints of each
      of the methods of the second group none of them can be considered universal.
      However, their joint application can be a promising approach to the assessment of
      the mechanisms that drive population abundance variability both in experimental
      and field studies.

PMID- 25985488
TI  - [Correlations between gynoecium morphology and ovary position in angiosperm
      flowers: roles of developmental and terminological constraints].
AB  - Angiosperm gynoecium consists of elementary units, called carpels. These can be
      free (apocarpy) or united (coenocarpy, or syncarpy in a wide sense). One of the
      most complicate problems of evolutionary morphology of angiosperms is
      distinguishing monomerous and pseudomonomerous gynoecia. The former are assumed
      to be derived by reduction of carpel number in apocarpous gynoecia, the latter by
      reduction of gynoecia with united carpels. Pseudomonomerous gynoecia have one
      fertile carpel and more or less prominent traces of sterile carpel(s). In extreme
      cases of reduction, pseudomonomerous gynoecia are very similar to monomerous,
      even though the two types have completely different evolutionary histories. G.B.
      Kedrov (1969) proposed a new approach to resolving the issue. Using the fact of
      absence of polymerous free-carpellate gynoecia with inferior ovaries, he
      suggested that there is a constraint against epigyny in plants with free carpels.
      Therefore, in taxa with disputable morphological interpretations, the gynoecium
      should be treated as pseudomonomerous (and not monomerous) if the ovary is
      inferior. A critical review of the concept of G.B. Kedrov showed that his ideas
      would suggest re-interpretation of widely accepted views on gynoecium morphology
      in several key families of basal angiosperms. An alternative view is proposed,
      that for most important types of epigyny in angiosperms, a "constraint" for a
      combination of inferior ovary and apocarpy is due to definition of the term
      "apocarpy" only. There is no biological sense in this "constraint". Existence of
      two other morphogenetic constraints is proposed: (1) against development of a
      typical inferior ovary in monomerous gynoecia with conduplicate carpel and (2)
      against a radial (sectorial) fusion of individual carpels with stamens or
      perianth members without fusion of these groups into an entire structure.
      Possible biological nature of these constraints is discussed.

PMID- 25985487
TI  - [Succession caused by beaver (Castor fiber L.) life activity: II. A refined
      Markov model].
AB  - The refined Markov model of cyclic zoogenic successions caused by beaver (Castor
      fiber L.) life activity represents a discrete chain of the following six states:
      flooded forest, swamped forest, pond, grassy swamp, shrubby swamp, and wet
      forest, which correspond to certain stages of succession. Those stages are
      defined, and a conceptual scheme of probable transitions between them for one
      time step is constructed from the knowledge of beaver behaviour in small river
      floodplains of "Bryanskii Les" Reserve. We calibrated the corresponding matrix of
      transition probabilities according to the optimization principle: minimizing
      differences between the model outcome and reality; the model generates a
      distribution of relative areas corresponding to the stages of succession, that
      has to be compared to those gained from case studies in the Reserve during 2002
      2006. The time step is chosen to equal 2 years, and the first-step data in the
      sum of differences are given various weights, w (between 0 and 1). The value of w
      = 0.2 is selected due to its optimality and for some additional reasons. By the
      formulae of finite homogeneous Markov chain theory, we obtained the main results
      of the calibrated model, namely, a steady-state distribution of stage areas,
      indexes of cyclicity, and the mean durations (M(j)) of succession stages. The
      results of calibration give an objective quantitative nature to the expert
      knowledge of the course of succession and get a proper interpretation. The 2010
      data, which are not involved in the calibration procedure, enabled assessing the
      quality of prediction by the homogeneous model in short-term (from the 2006
      situation): the error of model area distribution relative to the distribution
      observed in 2010 falls into the range of 9-17%, the best prognosis being given by
      the least optimal matrices (rejected values of w). This indicates a formally
      heterogeneous nature of succession processes in time. Thus, the refined version
      of the homogeneous Markov chain has not eliminated all the contradictions between
      the model results and expert knowledge, which suggests a further model
      development towards a "logically inhomogeneous" version or/and refusal to
      postulate the Markov property in the conceptual scheme of succession.

PMID- 25985489
TI  - [Localization and functions of mesenchymal stromal cells in vivo].
AB  - Studying mesenchymal stromal cells (MSC) is a very topical problem. Numerous
      experiments in vitro promoted understanding of MSC biology to a great extent.
      However, many aspects of their behavior in vivo still remain unclear. This review
      deals with MSC localization and functioning in an organism. MSC are present in
      various tissues, changing their numbers and traits during ontogenesis. Pericytes,
      or adventitial cells, can be considered as possible equivalents of MSC in vivo.
      Self-maintenance, proliferation, and differentiation of MSC are controlled by
      their tissue microenvironment that includes surrounding cells, soluble molecules,
      and extracellular matrix. At early stages of ontogenesis, MSC, probably, migrate
      throughout an organism. The migration occur also through a mature organism when
      tissues happen to be damaged. MSC move pointedly to the damaged parts and render
      a reparative effect which is due, first of all, to paracrine production of
      bioactive molecules. Immunomodulatory properties of MSC also play their role in
      tissues regeneration. An important function of MSC consists in creation of
      hematopoietic microenvironment. They secrete humoral regulators of hemopoiesis
      such as cytokines and chemoattractants. In addition, they interact with
      hemopoietic cells via surface molecules. Possibly, MSC sustain the stable
      functioning of other tissues as well. Their unique features make them quite
      attractive for clinical use, although successful introduction of MSC into medical
      practice requires their further studying.

PMID- 25985490
TI  - [Review of: G.S. Rozenberg "introduction to theoretical ecology'].

PMID- 25985491
TI  - The profession of nursing is rich in diversity in many ways.

PMID- 25985492
TI  - Development and initial validation of a Parkinson's disease caregiver strain risk
      screen.
AB  - BACKGROUND AND PURPOSE: Family caregivers face potential strain in caring for
      persons with Parkinson's disease because of the unpredictability of symptom
      presentation. The Caregiver Strain Risk Screen (CSRS) was developed and tested
      for initial validation. METHODS: Instrument item development was guided by focus
      group and interview data and a theoretical conceptualization of caregiver strain
      risk in caregivers of persons with Parkinson's disease. Caregivers of persons
      with Parkinson's disease (N = 217) provided data. RESULTS: Principal components
      analysis supported a 28-item instrument with 4 factors: self-preservation,
      nursing home consideration, coping through spirituality, and coping through
      formal support. CONCLUSION: The 28-item CSRS demonstrated acceptable validity and
      reliability in measuring the construct. Research using a new sample is underway
      to further psychometrically test and validate the CSRS through confirmatory
      factor analysis.

PMID- 25985493
TI  - An evaluation of chronic pain questionnaires in the adult population.
AB  - BACKGROUND AND PURPOSE: Considering pain's subjectivity, measurement and its
      processes are indispensable to clinicians and researchers. Development and
      testing methods of recently published chronic pain questionnaires were analyzed
      to determine the state of measurement in chronic pain. METHODS: There were 8
      questionnaires analyzed against 28 criteria, which combined specific testing
      standards and commonly accepted reliability statistics. RESULTS: Only 1
      questionnaire received a rating of good method quality. The 7 remaining
      questionnaires received a rating of poor method quality. CONCLUSIONS: Newly
      developed chronic pain self-report questionnaires revealed deficiencies in
      construction and testing methods. It is proposed that an adapted version of the
      Standards of Educational and Psychological Testing serves as a useful guide for
      developing and testing new health questionnaires.

PMID- 25985494
TI  - Development and psychometric evaluation of the Diabetes Self-Efficacy Scale.
AB  - BACKGROUND AND PURPOSE: No scales measure self-efficacy in women with Type 2
      diabetes. A scale was developed and tested. METHODS: Items generated, content
      validity index (CVI) assessed by experts, the 2-part Diabetes Self-Efficacy Scale
      (DSLF-I and DSLF-II) was piloted with 62 women, administered to 208 women, and
      then readministered to 30 women to determine initial reliability. Factor analysis
      was conducted for construct validity. Discriminant, convergent, and predictive
      validity was examined. RESULTS: The CVI index was 98%. Cronbach's alphas were
      0.88 (DSLF-I) and 0.82 (DSLF-II; pilot) and 0.87 and 0.86, respectively (main
      study); test-retest correlation was .60 (DSLF-I) and .69 (DSLF-II). There were 3
      factors that emerged: diabetes knowledge of self-care activity, diabetes diet
      self-care, and diabetes medication self-care. CONCLUSIONS: The Diabetes Self
      Efficacy Scale demonstrates good initial reliability and validity.

PMID- 25985495
TI  - Development and validation of the Perception of Self-Monitoring of Blood Glucose
      Scale in insulin-treated patients with diabetes.
AB  - BACKGROUND AND PURPOSE: The Perception of Self-Monitoring of Blood Glucose (P
      SMBG) scale was developed and validated to assess perceptions of self-monitoring
      of blood glucose (SMBG) in insulin-treated patients with diabetes. METHOD: An
      initial 68-item version of the P-SMBG has been evaluated by a panel of
      professionals and patients. A sample of 375 patients tested the revised scale.
      RESULTS: Factor analysis suggested a 19-item scale and a 2-factor structure,
      separating negatively and positively worded items. Cronbach's alpha was .84 and
      .72, and the intraclass correlation coefficient was .66 and .57, respectively for
      both factors. Item-total correlations were in the range of .23-.66.
      Convergent/divergent validity was confirmed for the negatively worded items.
      CONCLUSIONS: The final P-SMBG scale (21 items) can be used to assess positive and
      negative perceptions of SMBG in insulin-treated patients with diabetes.

PMID- 25985496
TI  - Psychometric properties of the Patient's Perception of Life on Hemodialysis
      Scale.
AB  - BACKGROUND AND PURPOSE: Hemodialysis (HD) is the main form of renal replacement
      therapy for many patients with end-stage renal disease. The purpose of this
      research is to assess reliability and validity of the Patient's Perception of
      Hemodialysis Scale. METHODS: Using a cross-sectional design and a convenient
      sample (n = 236), psychometric properties of the PPHS were examined. Validity was
      assessed using factor analysis and Pearson's correlation. Reliability was
      determined using Cronbach's alpha and test-retest stability (n = 30). RESULTS:
      Validity and reliability was supported. CONCLUSION: Examination of the PPHS
      provides evidence that it is a valid and reliable instrument for measuring
      disease-specific concerns with the HD patients, assessing how people experience
      life, and identifying ways in which people interpret the meaning of their
      physical and psychosocial health and adaptation to life on HD.

PMID- 25985497
TI  - Measuring relational care in nursing homes: psychometric evaluation of the
      Relational Care Scale.
AB  - BACKGROUND AND PURPOSE: The Relational Care Scale (RCS) is a Canadian evaluative
      instrument designed to measure nursing home residents' perceptions of care aides'
      relational abilities. Care aides' abilities to be reliable and empathetic with
      nursing home residents are very important determinants of quality of care, but
      few instruments are designed specifically for residents or focus exclusively on
      these determinants. Initially developed and tested in metropolitan teaching
      affiliated nursing homes in Ontario, we expanded testing by reevaluating the
      psychometric properties of the RCS in 5 rural nursing homes in British Columbia.
      METHOD: There were 62 residents living in 5 rural nursing homes who completed 3
      instruments: the RCS under investigation, the Experiences in Close Relationships
      Relationship Structures (ECR-RS) questionnaire to test for convergent validity,
      and the Lubben Social Network Scale-6 (LSNS-6) to test for discriminant validity.
      RESULTS: The reliability of the RCS was strongly supported (Cronbach's alpha =
      .90, item-total correlation > .77). Consistent with previous testing, a
      unidimensional internal structure was extracted. A moderate to strong correlation
      between the RCS and the Anxiety and Avoidance subscales of the ECR-RS supported
      convergent validity of the instrument. Last, partial support was obtained for the
      discriminant validity of the RCS. CONCLUSIONS: The RCS was easy to use for both
      residents and researchers. Expanded testing demonstrated its recurring
      reliability and validity.

PMID- 25985498
TI  - Psychometric properties of the Swedish version of the Self-Transcendence Scale
      among very old people.
AB  - BACKGROUND AND PURPOSE: This study tested the psychometric properties of a
      Swedish version of the Self-Transcendence Scale (STS). METHODS: Cohen's weighted
      kappa, agreement, absolute reliability, relative reliability, and internal
      consistency were calculated, and the underlying structure of the STS was
      established by exploratory factor analysis. There were 2 samples available: 1
      including 194 people aged 85-103 years and a convenience sample of 60 people aged
      21-69 years. RESULTS: Weighted kappa values ranged from .40 to .89. The
      intraclass correlation coefficient for the original STS was .763, and the least
      significant change between repeated tests was 6.25 points. CONCLUSION: The
      revised STS was found to have satisfactory psychometric properties, and 2 of the
      4 underlying dimensions in Reed's self-transcendence theory were supported.

PMID- 25985499
TI  - The Self-Efficacy for Functional Abilities Scale for older adults in long-term
      care: two-level exploratory and confirmatory factor analysis.
AB  - BACKGROUND AND PURPOSE: This study examines the underlying factor structure of
      the Self-Efficacy for Functional Abilities (SEFA) scale among older adults in
      long-term care settings. METHODS: A secondary analysis of SEFA data for 568
      residents in 16 long-term care facilities was applied. The sample was randomly
      split into 2 subsamples. A 2-level exploratory and confirmatory factor analysis
      adjusting for clustering effect of facilities was used to identify and determine
      the factor structures respectively. RESULTS: There were 1- and 2-factor models
      that were identified. Both models demonstrated acceptably mixed model fit. The 2
      factor model had poor discriminant validity with high correlation between factors
      (r = .92, p < .001). The single-factor model was considered valid with moderate
      correlation with function (r = .301, p < .001). CONCLUSIONS: The SEFA scale
      demonstrated a unidimensional construct among older adults in long-term care
      settings. Future testing is needed among other older adult populations.

PMID- 25985500
TI  - Nursing older people-competence evaluation tool: development and psychometric
      evaluation.
AB  - BACKGROUND AND PURPOSE: To evaluate the quality of care provided to older people,
      the competence of the nursing staff must be measured. This study evaluates a new
      instrument called Nursing Older People-Competence Evaluation Tool (NOP-CET).
      METHODS: A 65-item questionnaire was completed by 1,016 community-based nursing
      staff and evaluated for validity, reliability, precision, interpretability,
      acceptability, and feasibility. RESULTS: The survey demonstrated good content
      validity; conceptually coherent factor structure explaining 54.98% (knowledge
      items), 65.03% (skills items), and 52.83% (personal attribute items) of the total
      variance; and internal consistency (.77-.93). CONCLUSIONS: The NOP-CET showed
      good validity and reliability as a measure of community-based nursing staff
      competence and may be used in further investigations of competence in older
      people nursing.

PMID- 25985501
TI  - Psychometric analysis of the Multidimensional Fatigue Inventory in a sample of
      persons treated for myocardial infarction.
AB  - BACKGROUND AND PURPOSE: Fatigue after myocardial infarction is a frequent and
      distressing symptom in the early recovery phase. The purpose of this study is to
      psychometrically evaluate the Multidimensional Fatigue Inventory (MFI-20).
      METHODS: The MFI-20 was evaluated using Rasch analysis. RESULTS: The result
      showed that the MFI-20 can be used to obtain a global score reflecting an
      underlying unidimensional trait of fatigue; a transformation of the summarized
      raw scale scores into interval scale scores could be made. Also, 4 of the 5
      original dimensions separately fitted the Rasch model. CONCLUSIONS: Calculation
      of a global score increases the possibility of identifying persons experiencing
      fatigue after myocardial infarction, and using the MFI-20 dimension scores
      increases the possibility of determining each person's specific fatigue profile.

PMID- 25985502
TI  - Nursing Educational Motivation and Barriers Inventory.
AB  - BACKGROUND AND PURPOSE: The major purposes of the study are revision of the
      Nursing Educational Motivation and Barriers Inventory (NEMBI) and translation of
      it into Arabic. METHODS: NEMBI was translated into Arabic, then back-translated
      to ensure the accuracy of the translation. The translation and back-translation
      of NEMBI were accurate and identical. A panel of experts provided content
      validation. Reliability was evaluated in a pilot test. For the larger study, 158
      Saudi nurses completed the NEMBI. RESULTS: Exploratory factor analysis yielded 8
      factors. NEMBI is a valid and reliable tool for use in Arabic-speaking
      populations. CONCLUSION: As nursing education is transformed in Arabic-speaking
      norms, this tool provides a valid and reliable means for examining motivational
      factors that influence nurses' decision to return to school to advance their
      education.

PMID- 25985503
TI  - Reliability of vascular access site bruise measurement.
AB  - BACKGROUND AND PURPOSE: Vascular access site (VAS) bruising is common following
      invasive cardiac procedures. The extent of VAS bruising is underreported because
      of the lack of reliable measurement methods. This study examined the reliability
      of linear measurement and planimetry to measure VAS bruise size. METHODS: There
      were 40 participants with VAS bruising after invasive cardiac procedures who
      completed VAS bruise measurement. Participants, a principal investigator, and a
      research assistant completed measurements independently. Inter-rater reliability
      was determined using intraclass correlation coefficient (ICC), 2-way random
      effects model. RESULTS: The ICC for linear measurement and planimetry was high
      (.929 and .914 respectively). Both methods were reliable measures of VAS bruise
      size. CONCLUSIONS: Linear measurement or planimetry can be used with confidence
      to measure VAS bruising in clinical and research contexts.

PMID- 25985504
TI  - Preface. International best practices in health care management.

PMID- 25985505
TI  - Inernational research in health care management: its need in the 21st century,
      methodological challenges, ethical issues, pitfalls, and practicalities.
AB  - PURPOSE: This commentary argues in favor of international research in the 21st
      century. Advances in technology, science, communication, transport, and
      infrastructure have transformed the world into a global village. Industries have
      increasingly adopted globalization strategies. Likewise, the health sector is
      more internationalized whereby comparisons between diverse health systems,
      international best practices, international benchmarking, cross-border health
      care, and cross-cultural issues have become important subjects in the health care
      literature. The focus has now turned to international, collaborative, cross
      national, and cross-cultural research, which is by far more demanding than
      domestic studies. In this commentary, we explore the methodological challenges,
      ethical issues, pitfalls, and practicalities within international research and
      offer possible solutions to address them. DESIGN/METHODOLOGY/APPROACH: The
      commentary synthesizes contributions from four scholars in the field of health
      care management, who came together during the annual meeting of the Academy of
      Management to discuss with members of the Health Care Management Division the
      challenges of international research. FINDINGS: International research is worth
      pursuing; however, it calls for scholarly attention to key methodological and
      ethical issues for its success. ORIGINALITY/VALUE: This commentary addresses
      salient issues pertaining to international research in one comprehensive account.

PMID- 25985506
TI  - Defining world-class care in academic medicine: enablers and challenges.
AB  - PURPOSE: Interest has grown among U.S. academic medical centers in developing
      international benchmarks for excellence in process and outcomes. Drivers behind
      this trend, as well as barriers to the development of useful benchmarks, are
      explored in this invited commentary. DESIGN/METHODOLOGY/APPROACH: The commentary
      is based on the authors' conversations with members of the U.S. Cooperative for
      International Patient Programs as well as the University Healthsystem Consortium
      (UHC). FINDINGS: Six key themes are summarized in this commentary, including four
      key drivers and two barriers. ORIGINALITY/VALUE: The practice-based perspectives
      this commentary summarizes provide a useful starting point for researchers and
      practitioners interested in establishing international comparison with the United
      States.

PMID- 25985507
TI  - International "best practices" in health care: the roles of context and
      innovation.
AB  - PURPOSE: Explores recent approaches to international best practices and how they
      relate to context and innovation in health services. DESIGN/METHODOLOGY/APPROACH:
      Critical review of existing research on best practices and how they created,
      diffused, and translate in the international setting. FINDINGS: Best practices
      are widely used and discussed, but processes by which they are developed and
      diffused across international settings are not well understood. RESEARCH
      IMPLICATIONS: Further research is needed on innovation and dissemination of best
      practices internationally. ORIGINALITY/VALUE: This commentary points out
      directions for future research on innovation and diffusion of best practices,
      particularly in the international setting.

PMID- 25985508
TI  - The link between health governance models and global health innovation: an
      exploration of OECD nations.
AB  - PURPOSE: While there is established research that explores individual innovations
      across countries or developments in a specific health area, there is less work
      that attempts to match national innovations to specific systems of health
      governance to uncover themes across nations. DESIGN/METHODOLOGY/APPROACH: We used
      a cross-comparison design that employed content analysis of health governance
      models and innovation patterns in eight OECD nations (Australia, Britain, Canada,
      France, Germany, The Netherlands, Switzerland, and the United States). FINDINGS:
      Country-level model of health governance may impact the focus of health
      innovation within the eight jurisdictions studied. Innovation across all
      governance models has targeted consumer engagement in health systems, the
      integration of health services across the continuum of care, access to care in
      the community, and financial models that drive competition. ORIGINALITY/VALUE:
      Improving our understanding of the linkage between health governance and
      innovation in health systems may heighten awareness of potential enablers and
      barriers to innovation success.

PMID- 25985509
TI  - Good practices in health care "management experimentation models": insights from
      an international public-private partnership on transplantation and advanced
      specialized therapies.
AB  - PURPOSE: The research analyzes good practices in health care "management
      experimentation models," which fall within the broader range of the integrative
      public-private partnerships (PPPs). Introduced by the Italian National Healthcare
      System in 1991, the "management experimentation models" are based on a public
      governance system mixed with a private management approach, a patient-centric
      orientation, a shared financial risk, and payment mechanisms correlated with
      clinical outcomes, quality, and cost-savings. This model makes public hospitals
      more competitive and efficient without affecting the principles of universal
      coverage, solidarity, and equity of access, but requires higher financial
      responsibility for managers and more flexibility in operations.
      METHODOLOGY/APPROACH: In Italy the experience of such experimental models is
      limited but successful. The study adopts the case study methodology and refers to
      the international collaboration started in 1997 between two Italian hospitals and
      the University of Pittsburgh Medical Center (UPMC - Pennsylvania, USA) in the
      field of organ transplants and biomedical advanced therapies. FINDINGS: The
      research allows identifying what constitutes good management practices and
      factors associated with higher clinical performance. Thus, it allows to
      understand whether and how the management experimentation model can be
      implemented on a broader basis, both nationwide and internationally. However, the
      implementation of integrative PPPs requires strategic, cultural, and managerial
      changes in the way in which a hospital operates; these transformations are not
      always sustainable. ORIGINALITY/VALUE: The recognition of ISMETT's good
      management practices is useful for competitive benchmarking among hospitals
      specialized in organ transplants and for its insights on the strategies
      concerning the governance reorganization in the hospital setting. Findings can be
      used in the future for analyzing the cross-country differences in productivity
      among well-managed public hospitals.

PMID- 25985510
TI  - Rising labor costs, earnings management, and financial performance of health care
      providers around the world.
AB  - PURPOSE: Amid increasing interest in how government regulation and market
      competition affect the cost and financial sustainability in health care sector,
      it remains unclear whether health care providers behave similarly to their
      counterparts in other industries. The goal of this chapter is to study the degree
      to which health care providers manipulate accruals in periods of financial
      difficulties caused, in part, by the rising costs of labor. METHODOLOGY: We
      collected the financial information of health care provider in 43 countries from
      1984 to 2013 and conducted a pooled cross-sectional study with country and year
      fixed-effects. FINDINGS: The empirical evidence shows that health care providers
      with higher wage costs are more likely to smooth their earnings in order to
      maintain financial sustainability. ORIGINALITY/VALUE: The finding of this study
      not only informs regulators that earnings management is pervasive in health care
      organizations around the world, but also contributes to the studies of financial
      booktax reporting alignment, given the existing empirical evidence linking
      earnings management to corporate tax avoidance in this very sector.

PMID- 25985511
TI  - Best practices to promote occupational safety and satisfaction: a comparison of
      three North American hospitals.
AB  - PURPOSE: Hospitals in North America consistently have employee injury rates
      ranking among the highest of all industries. Organizations that mandate workplace
      safety training and emphasize safety compliance tend to have lower injury rates
      and better employee safety perceptions. However, it is unclear if the work
      environment in different national health care systems (United States vs. Canada)
      is associated with different employee safety perceptions or injury rates. This
      study examines occupational safety and workplace satisfaction in two different
      countries with employees working for the same organization. METHODOLOGY/APPROACH:
      Survey data were collected from environmental services employees (n = 148) at
      three matched hospitals (two in Canada and one in the United States). The
      relationships that were examined included: (1) safety leadership and safety
      training with individual/unit safety perceptions; (2) supervisor and coworker
      support with individual job satisfaction and turnover intention; and (3) unit
      turnover, labor usage, and injury rates. FINDINGS: Hierarchical regression
      analysis and ANO VA found safety leadership and safety training to be positively
      related to individual safety perceptions, and unit safety grade and effects were
      similar across all hospitals. Supervisor and coworker support were found to be
      related to individual and organizational outcomes and significant differences
      were found across the hospitals. Significant differences were found in injury
      rates, days missed, and turnover across the hospitals. ORIGINALITY/VALUE: This
      study offers support for occupational safety training as a viable mechanism to
      reduce employee injury rates and that a codified training program translates
      across national borders. Significant differences were found.between the hospitals
      with respect to employee and organizational outcomes (e.g., turnover). These
      findings suggest that work environment differences are reflective of the
      immediate work group and environment, and may reflect national health care system
      differences.

PMID- 25985512
TI  - International comparison of preoperative testing and assessment protocols and
      best practices to reduce surgical care costs: a systematic literature review.
AB  - PURPOSE: Health care institutions in many Western countries have developed
      preoperative testing and assessment guidelines to improve surgical outcomes and
      reduce cost of surgical care. The aims of this chapter are to (1) summarize the
      literature on the effect of preoperative testing on clinical outcomes,
      efficiency, and cost; and (2) to compare preoperative testing guidelines
      developed in the United States, the United Kingdom, and Canada.
      DESIGN/METHODOLOGY/APPROACH: We reviewed the literature from 1975 to 2014 for
      studies and preoperative testing guidelines. FINDINGS: We identified 29 empirical
      studies and 8 country-specific guidelines for review. Most studies indicate that
      preoperative testing is overused and comes at a high cost. Guidelines are tied to
      payment only in one country studied. This is the most recent review of the
      literature on preoperative testing and assessment with a focus on quality of
      care, efficiency, and cost outcomes. In addition, this chapter provides an
      international comparison of preoperative guidelines.

PMID- 25985513
TI  - Process optimization in the emergency department by the use of point-of-care
      testing (POCT) in life-threatening conditions: comparative best practice examples
      from Germany and Malta.
AB  - PURPOSE: Point-of-care testing (POCT) at the Emergency Department (ED) attains
      better objectives in patient care while aiming to achieve early diagnosis for
      faster medical decision-making. This study assesses and compares the benefits of
      POCT in the ED in Germany and Malta, while considering differences in their
      health systems. METHODOLOGY/APPROACH: This chapter utilizes multiple case study
      approach using Six Sigma. The German case study assesses the use of POCT in acute
      coronary syndrome patients, compared to the central lab setting. The Maltese case
      study is a pilot study of the use of medical ultrasonography as a POCT to detect
      abdominal free fluid in post-blunt trauma. FINDINGS: This study provides clear
      examples of the effectiveness of POCT in life-threatening conditions, as compared
      to the use of traditional central lab or the medical imaging department.
      Therapeutic quality in the ED and patient outcomes directly depend upon
      turnaround time, particularly for life-threatening conditions. Faster turnaround
      time not only saves lives but reduces morbidity, which in the long-term is a
      critical cost driver for hospitals. ORIGINALITY/VALUE: The application of Six
      Sigma and the international comparison of POCT as best practice for life
      threatening conditions in the ED.

PMID- 25985514
TI  - International benchmarking and best practice management: in search of health care
      and hospital excellence.
AB  - PURPOSE: Hospitals worldwide are facing the same opportunities and threats: the
      demographics of an aging population; steady increases in chronic diseases and
      severe illnesses; and a steadily increasing demand for medical services with more
      intensive treatment for multi-morbid patients. Additionally, patients are
      becoming more demanding. They expect high quality medicine within a dignity
      driven and painless healing environment. The severe financial pressures that
      these developments entail oblige care providers to more and more cost-containment
      and to apply process reengineering, as well as continuous performance improvement
      measures, so as to achieve future financial sustainability. At the same time,
      regulators are calling for improved patient outcomes. Benchmarking and best
      practice management are successfully proven performance improvement tools for
      enabling hospitals to achieve a higher level of clinical output quality, enhanced
      patient satisfaction, and care delivery capability, while simultaneously
      containing and reducing costs. APPROACH: This chapter aims to clarify what
      benchmarking is and what it is not. Furthermore, it is stated that benchmarking
      is a powerful managerial tool for improving decision-making processes that can
      contribute to the above-mentioned improvement measures in health care delivery.
      The benchmarking approach described in this chapter is oriented toward the
      philosophy of an input-output model and is explained based on practical
      international examples from different industries in various countries. FINDINGS:
      Benchmarking is not a project with a defined start and end point, but a
      continuous initiative of comparing key performance indicators, process
      structures, and best practices from best-in-class companies inside and outside
      industry. Benchmarking is an ongoing process of measuring and searching for best
      in-class performance: Measure yourself with yourself over time against key
      performance indicators. Measure yourself against others. Identify best practices.
      Equal or exceed this best practice in your institution. Focus on simple and
      effective ways to implement solutions. Comparing only figures, such as average
      length of stay, costs of procedures, infection rates, or out-of-stock rates, can
      lead easily to wrong conclusions and decision making with often-disastrous
      consequences. Just looking at figures and ratios is not the basis for detecting
      potential excellence. It is necessary to look beyond the numbers to understand
      how processes work and contribute to best-in-class results. Best practices from
      even quite different industries can enable hospitals to leapfrog results in
      patient orientation, clinical excellence, and cost-effectiveness.
      ORIGINALITY/VALUE: Despite common benchmarking approaches, it is pointed out that
      a comparison without "looking behind the figures" (what it means to be familiar
      with the process structure, process dynamic and drivers, process
      institutions/rules and process-related incentive components) will be extremely
      limited referring to reliability and quality of findings. In order to demonstrate
      transferability of benchmarking results between different industries practical
      examples from health care, automotive, and hotel service have been selected.
      Additionally, it is depicted that international comparisons between hospitals
      providing medical services in different health care systems do have a great
      potential for achieving leapfrog results in medical quality, organization of
      service provision, effective work structures, purchasing and logistics processes,
      or management, etc.

PMID- 25985515
TI  - Concluding remarks. Best practices across international boundaries.

PMID- 25985516
TI  - [Regulation of global transcriptional factor cyclic AMP receptor protein and its
      metabolic engineering application in Escherichia coli].
AB  - Cyclic amp receptor protein (CRP) is a global transcriptional factor in many
      prokaryotes, capable of governing nearly half of the total genes in Escherichia
      coli. Through the method of error-prone PCR or DNA shuffling, we can first obtain
      CRP mutant library and then get the expected cell phenotype with enhanced
      resistance. In this article, we reviewed the following desired phenotype:
      enhanced tolerance towards oxidative stress, improved osmotolerance, enhanced
      organic solvent (toluene) tolerance, improved acetate tolerance of E. coli
      fermentation and improved ethanol tolerance during bio-ethanol production. We
      then concluded that CRP can also be applied in other host cells to get desired
      phenotypes. Last, we predicted potential applications of mutant CRP
      transcriptional factor.

PMID- 25985517
TI  - [Preparation and identification of monoclonal antibodies against infectious
      bursal disease virus (IBDV) VP4].
AB  - Infectious bursal disease virus (IBDV) VP4 plays an important role in
      immunosuppression of host. In order to develop monoclonal antibodies (McAbs)
      against VP4, we vaccinated BALB/c mice with His-VP4, screened and subcloned
      positive clones. We established 4 hybridoma cell lines that stably secreted McAbs
      against VP4 and named these cell lines 3B3, 3H11, 4C8 and 4G6, respectively. We
      tested the dissociation constant (Kd) of these McAbs, and found that their K(d)s
      were 4.61 x 10(-11), 1.71 x 10(-10), 4.26 x 10(-11), 5.02 x 10(-11),
      respectively. The isotypes of these McAbs were determined to be IgG1, IgG1, IgG2b
      and IgG1. These McAbs specifically bound to VP4 in IBDV infected DF-1 cells as
      demonstrated by Western blotting analysis and fluorescence antibody assay. These
      McAbs would help to detect IBDV infection and to analyze the biological
      activities of IBDV VP4.

PMID- 25985518
TI  - [Cloning, expression and protective efficacy evaluation of radiation sensitive
      protein 23 (RAD23) from Schistosoma japonicum].
AB  - Radiation sensitive protein 23 (RAD23) is a nucleotide excision repair (NER)
      protein that plays an important role in Ubiquitin-proteasome pathway (UPP).
      Schistosoma japonicum radiation sensitive protein23 (SjRAD23) cDNA sequences were
      amplified by PCR and cloned into pET28a (+) vector to construct recombinant
      expression plasmid pET28a(+)-SjRAD23. The recombinant protein was expressed as
      both inclusion bodies and the supernatant in Escherichia coli BL21 (DE3) cell.
      Immunofluorescence observation shows that SjRAD23 was mainly distributed on the
      tegument surface of the worms. ELISA assay reveals that specific IgG, IgG1 and
      IgG2a antibodies could be detected in the sera of rSjRAD23 immunized mice.
      Western blotting analysis shows that the recombinant SjRAD23 could be recognized
      by serum specific to soluble adult worm antigen of S. japonicum. BALB/c mice
      vaccinated with rSjRAD23 combined with 206 adjuvant revealed 35.94% worm
      reduction and 40.59% liver egg reduction when compared with that of the adjuvant
      control

PMID- 25985519
TI  - [Immunogenicity of recombinant Lactobacillus casei expressing VP2 protein of
      infectious bursal disease virus in chickens].
AB  - In order to determine immunogenicity and protective effect in chickens, we used
      the IBDV (Infectious bursal disease virus)-Vp2/Lactobacillus casei as antigen
      transfer system. First, the immunized and control chickens were challenged by
      IBDV/DQ at lethal dose to determine the protective ratio. Second, chickens were
      orallyand intranasally vaccinated twice with 10(9) CFU/mL pLA-VP2/L. casei,
      pLA/L. casei and PBS as negativecontrol and commercial vaccine as positive
      control. The bursa injury and the lesion score wererecorded post challenge. The
      level of specific IgG and sIgA in pLA-VP2/L. casei and positive control groups
      was significantly higher than that in negativecontrol groups. The protection
      efficacy in pLA-VP2/L. casei oral group was higher than that inintranasal group.
      The SI. of pLA-VP2/L. casei oral group was significant higher than other groups.
      The lesion score indicated the pLA-VP2/L. casei was safer than commercial vaccine
      for bursa. Collectively, the pLA-VP2/L. casei could be a vaccine candidate for
      IBDV.

PMID- 25985521
TI  - [Purification of enramycin by macroporous resin adsorption and reversed phase
      chromatography purification].
AB  - Enramycin is a polypeptide antibiotic and new, safe animal feed additive. A new
      purification process was developed, based on pre-purification by macroporous
      resin and refining by reversed phase chromatography. AB-8 macroporous resin was
      used for the pre-purification process of enramycin, with an elution buffer of
      0.012 mol/L aqueous HCl solution-methanol (50: 50, V/V). Then, enramycin a and
      enramycin b were separated effectively by C18 reversed phase chromatography, with
      a elution buffer of 0.05 mol/L aqueous KH2PO4 solution-acetonitrile (70: 30, V/V,
      pH 4.5). The purities of enramycin a and enramycin b were up to 98.5% and 98.0%,
      respectively. The yield reached 29.2%. This study would provide a useful
      reference for the preparation of enramycin a and enramycin b with a high purity.

PMID- 25985520
TI  - [Effects of two UDP-glucose dehydrogenases on hyaluronic acid biotransformation].
AB  - We amplified genes encoding UDP-glucose dehydrogenase, ecohasB from Escherichia
      coli and spyhasB from Streptococcus pyogenes. Both ecohasB and spyhasB were
      inserted into T7 expression vector pRX2 to construct recombinant plasmids pRXEB
      and pRXSB, and to express in E. coli BL21(DE3). After nickel column purification
      of UDP-glucose dehydrogenases, the enzymes were characterized. The optimum
      reaction condition of spyHasB was at 30  degrees C and pH 10. The specific
      activity reached 12.2 U/mg under optimum condition. The optimum reaction
      condition of ecoHasB was at 30  degrees C and pH 9. Its specific activity reached
      5.55 U/mg under optimum condition. The pmuhasA gene encoding hyaluronic acid
      synthase was amplified from Pasteurella multocida and ligated with ecohasB and
      spyhasB to construct the coexpression vectors pBPAEB and pBPASB, respectively.
      The co-expression vectors were transformed into E. coli BW25113. Hyaluronic acid
      (HA) was produced by biotransformation and the conditions were optimized. When
      recombinant strains were used to produce hyaluronic acid, the higher the activity
      of UDP-glucose dehydrogenase was, the better its stability was, and the higher
      the HA production could reach. Under the optimal conditions, the yields of HA
      produced by pBPAEB/BW25113 and pBPASB/BW25113 in shake flasks were 1.52 and 1.70
      g/L, respectively, and the production increased more than 2-3 folds as previously
      reported.

PMID- 25985522
TI  - [Characterization and subcellular localization of two SBP genes and their
      response to abiotic stress in soybean (Glycine max (L.) Merr.)].
AB  - High temperature and humidity stress during seed growth and development of spring
      soybean can result in seed deterioration in South China. We isolated two genes
      (GmSBP and GmSBPL) encoding putative SBP proteins from soybean (Glycine max (L.)
      Merr.) to study their biological functions and response to abiotic stress,. The
      two SBP proteins are hydrophilic and incomplete membrane ones. Real-time
      quantitative (RT-PCR) analysis reveals that the expression of the two genes in
      the developing seeds of the seed deterioration resistant cultivar Xiangdou No. 3
      and sensitive cultivar Ningzhen No. 1 was significantly affected by high
      temperature and humidity treatment. Meanwhile, the levels of sucrose and soluble
      sugar in the developing seeds of both cultivars were also affected under high
      temperature and humidity stress. During seed growth and development, the
      expression of the two genes as well as the levels of sucrose and soluble sugar
      reached the highest at 30 days after flower. GmSBP2 and GmSBPL were found to be
      differentially expressed in different soybean tissues. Sub-cellular localization
      indicated that two genes were located in cytoplasm and cell membrane. Our results
      indicate that GmSBP2 and GmSBPL might be involved in the response to abiotic
      stress, which will enrich our understanding of pre-harvest seed deterioration and
      resistance in soybean from one side.

PMID- 25985523
TI  - [Gene expression of AAV-ITR ssDNA mini vector in skeletal muscle of mice].
AB  - AAV-ITR single strand DNA mini vector (AAV-ITR ssDNA mini vector) is a novel gene
      expression vector based on AAV-ITR. We have shown efficient gene expression of
      AAV-ITR ssDNA mini vector in HEK 293T. Here, we studied the efficacy of gene
      expression of AAV-ITR ssDNA mini vector in vivo. We injected the skeletal muscle
      of ICR mice separately with equal molars of AAV-ITR ssDNA mini vector, ITR
      mutated AAV-ITR single strand DNA mini vector (AAV-ITRmm ssDNA mutant vector),
      AAV-ITR dsDNA and pUC57-minivector-GFP, combined with TurboFect. Florescence
      microscope analysis of skeletal muscle section shows that AAV-ITR ssDNA mini
      vector had higher expression efficiency and longer expression period. We
      extracted DNA from the muscle three months after injection and quantified three
      vectors by Real-time PCR. RT-PCR analysis shows that there were highest copy
      numbers of AAV-ITR ssDNA mini vector existing in muscle. Stable existing of AAV-
      TR ssDNA mini vector in muscle could be the molecular basis of long term gene
      expression of the vector. The results suggest that AAV-ITR ssDNA mini vector
      might be a promising vector for gene therapy.

PMID- 25985524
TI  - [Construction and identification of luciferase reporter gene containing mouse T
      bet promoter].
AB  - The aim of this study is to clone the mouse T-bet promoter and enhancer,
      construct and identify the firefly luciferase reporter gene plasmid pGL4.10
      TBX21pr-CNS for T-bet transcription regulation study and its function in
      signaling of multiple sclerosis. The promoter and CNS of T-bet were predicted by
      bioinformatics assay. The predicted fragment of mouse T-bet promoter plus CNS was
      amplified by PCR and cloned into pGL4.10. The recombinant plasmid pGL4.10-TBX21pr
      CNS was transferred into Escherichia coli DH5alpha. The positive clone was
      identified by double digestion with Kpn I and Sfi I and DNA sequencing. Finally,
      pGL4.10-TBX21pr-CNS was cotransfected with pRL-TK into 293T cells and Jurkat
      cells, pRL-TK and pGL4.10 as a control. The luciferase activity in 293T cells (P
      = 0.012 2) and Jurkat cells (P = 0.002 2) was higher than that of the control
      group. A fragment of 1 028 bp mouse T-bet promoter plus 1 308 bp CNS was
      successfully cloned and the firefly luciferase reporter gene plasmid pGL4.10
      TBX21pr-CNS was constructed. In 293T cells and Jurkat cells, pGL4.10-TBX21pr-CNS
      has the promoter functions. This work offers a basic material for the research of
      T-bet transcription.

PMID- 25985525
TI  - [Induction and in vitro culture of hairy roots of Dianthus caryophyllus and its
      plant regeneration].
AB  - To use Agrobacterium rhizogenes-induced hairy roots to create new germplasm of
      Dianthus caryophyllus, we transformed D. caryophyllus with A. rhizogenes by leaf
      disc for plant regeneration from hairy roots. The white hairy roots could be
      induced from the basal surface of leaf explants of D. caryophyllus 12 days after
      inoculation with A. rhizogenes ATCC15834. The percentage of the rooting leaf
      explants was about 90% 21 days after inoculation. The hairy roots could grow
      rapidly and autonomously in liquid or solid phytohormone-free MS medium. The
      transformation was confirmed by PCR amplification of rol gene of Ri plasmid and
      silica gel thin-layer chromatography of opines from D. caryophyllus hairy roots.
      Hairy roots could form light green callus after cultured on MS+6-BA 1.0-3.0 mg/L
      + NAA 0.1-0.2 mg/L for 15 days. The optimum medium for adventitious shoots
      formation was MS + 6-BA 2.0 mg/L + NAA 0.02 mg/L, where the rate of adventitious
      shoot induction was 100% after cultured for 6 weeks. The mean number of
      adventitious shoot per callus was 30-40. The adventitious shoots can form roots
      when cultured on phytohormone-free 1/2 MS or 1/2 MS +0.5 mg/L NAA for 10 days.
      When the rooted plantlets transplanted in the substrate mixed with perlite sand
      and peat (volume ratio of 1:2), the survival rate was above 95%.

PMID- 25985526
TI  - [Efficient transient expression to analyze miRNA targets in rice protoplasts].
AB  - Compared with the transgenic approach, transient assays provide a convenient
      alternative to analyze gene expression. To analyze the relationship between
      miRNAs and their target genes, a rice protoplast system to detect target gene
      activity was established. The MIRNA and GFP-fused target sequence (or GFP-fused
      mutated sequence as a non-target control) were constructed into the same plasmid,
      and then delivered into rice protoplasts. The GFP expression level decreased
      significantly when the protoplasts were transfected with the plasmid containing
      GFP-fused target compared to that of the plasmid with non-target sequence either
      by fluorescence microscopy or qRT-PCR method. Two microRNA genes, osaMIR156 and
      osaMIR397, and their target sequences were used to prove the feasibility of the
      rice protoplast transient assay system. This method will facilitate large-scale
      screening of rice miRNA target in vivo, and may be suitable for functional
      analysis of miRNAs of other monocot plants that might share the evolutionarily
      conserved small RNA processing system with rice.

PMID- 25985527
TI  - [Assembling of an ammonium transporter gene in Salicornia europaea by expression
      pattern analysis of Unigene in transcriptome].
AB  - RNA-seq can help us quickly obtain the whole transcriptome sequences of species
      under different conditions. Many Unigenes that are assembled by raw reads always
      do not contain complete open reading frame (ORF). In addition, it also has some
      redundancy in transcriptome library. Some Unigenes in the library, although
      belong to one transcript, cannot be assembled without overlapping. We found five
      incomplete Unigenes annotated ammonium transporter (AMT) from Salicornia europaea
      transcriptome, in which two Unigenes (Uni4 and Uni5) had identical expression
      patterns across four transcriptomes. The two Unigenes may come from one
      transcript. Analyzing the Unigene position of transcript by NCBI blastx, we found
      that Uni4 and Uni5 respectively located in 5' end and 3' end compared with the
      reference transcript, and an unknown gap of 120 bp may exist in a hypothetic
      transcript to which Uni4 and Uni5 both belong. To verify the hypothesis, single
      forward primer and single reverse primers were respectively designed on Uni4 and
      Uni5, and a fragment with about 800 bp was generated by PCR. Then it was
      sequenced and aligned with Uni4 and Uni5. Finally, we assembled a sequence with 1
      667 bp, which contains a complete ORF (1 482 bp, coding 494 amino acids). It
      belongs to amt1 subfamily and was named Seamt1 via the phylogenetic analysis. It
      was pointed by bioinformatics tools that SeAMT1 protein conformed to the AMT
      characteristics of other species. This work clustered expression pattern to
      explore the Unigenes of one transcript, and the feasibility of this method was
      validated through the other two groups of Unigenes. The handy method will benefit
      extension and assembling of Unigene in transcriptome, it also helps achieve the
      complete ORF and gene function.

PMID- 25985528
TI  - [Molecular cloning, prokaryotic expression and double-antibody sandwich ELISA
      development of 17beta-hsd10 in mouse].
AB  - We expressed 17-hydroxysteroid dehydrogenase10 (17beta-hsd10) recombinant
      protein, prepared anti-17beta- hsd10 polyclonal antibodies and established
      sandwich enzyme linked immunosorbent assay (ELISA) test for detection of 17beta
      hsd10. RT-PCR was used to get the gene of 17beta-hsd10 of mouse liver, and a
      prokaryotic protein expression system pET 15b-17beta-hsd10/Escherichia coli BL21
      (DE3) which induced with isopropyl-1-thio-beta-galactopyranoside (IPTG) for
      recombinant protein expression was constructed subsequently. The target protein
      purified using His-Binding-resin column was used to immunize BALB/c mice and
      rabbits, serum total IgGs from immunized animals were purified by ammonium
      sulfate precipitation method. We established a Double-antibody Sandwich enzyme
      linked immunosorbent assay about 17beta-hsd10 using the two antibodies we
      prepared. We got the concentration of 1.5 mg/mL of 17beta-hsd10 protein with
      molecular weight of 29.5 kDa, and polyclonal antibodies from mouse and rabbit
      with the tite 1.25 x 10(4) and 2.5 x 10(4) respectively. The concentration of 0.1
      g/mL of 17beta-hsd10 can be detected by the Double-antibody Sandwich ELISA we
      established, and the assay was sensitive and specific. It can be widely used in
      clinical and experimental study.

PMID- 25985529
TI  - [Optimization of whole-cell biocatalysis for phenylacetyl- 7
      aminodeacetoxycephalosporanic acid production].
AB  - Cephalosporins are widely used antibiotics owing to their broad activity spectra
      and low toxicity. Many of these medically important compounds are made chemically
      from 7-aminodeacetoxycephalosporanic acid. At present, this intermediate is made
      by synthetic ring-expansion of the inexpensive penicillin G to form G-7-ADCA,
      followed by enzymatic removal of the side chain to obtain 7-ADCA. The chemical
      synthetic process is expensive, complicated and environmentally unfriendly.
      Environmentally compatible enzymatic process is favorable compared with chemical
      synthesis. In our previous research, metabolic engineered Escherichia coli strain
      (H7/PG15) was constructed and used as whole-cell biocatalyst for the production
      of G-7-ADC with penicillin G as substrate. The whole-cell biocatalysis was
      studied by single factor experiment, including the composition of substrates and
      the conversion conditions (OD600, pH, concentration of penicillin G, MOPS,
      glucose, time and FeSO4). After optimization, 15 mmol/L of G-7-ADCA was obtained.
      The process is convenient, efficient and economic. This work would facilitate the
      industrial manufacturing and further product research.

PMID- 25985530
TI  - [Producing Ad-IFN gamma by suspension culture of HEK293 cells in a disposable
      bioreactor].
AB  - Adenovirus vectors are promising delivery systems for gene therapy. We
      established a new process for clinic trial of recombinant adenovirus vectors
      using a novel disposable bioreactor. The suspension HEK293 cells were inoculated
      into a 5 L disposable bioreactor with parameters control of pH, DO, agitation and
      temperature. After 6 days of a fed-batch culture, the final cell density reached
      2.0 x 10(6) cells/mL. The culture was infected with Ad-IFNgamma at an MOI of 30.
      The harvest was performed at approximately 48 h post-infection and crude viral
      lysate was obtained after 3 freeze/thaw cycles and centrifugation. The maximum
      titers of crude viral lysate was 1.49 x 10(13) Infectious units (IFU) and the
      bulk product specific was 3,800 IFU/cell. Purified Ad-IFNgamma by anion-exchange
      chromatography and the final recovery of infectious unit reached 35.9%. The
      result demonstrates that an efficient and stable process of producing Ad-IFNgamma
      using a disposable fed-batch bioreactor is established.

PMID- 25985532
TI  - NEHA has a new executive director.

PMID- 25985533
TI  - UVA and cutaneous melanoma incidences: spatial patterns and communities at risk.
AB  - The authors examined the associations of melanoma of the skin (i.e., cutaneous
      melanoma) incidence rates with specific ultraviolet (UV) exposure metrics across
      the U.S. No correlation between the age-adjusted incidence rates of cutaneous
      melanoma and annual average, maximum, and cumulative UV levels was observed. The
      authors then estimated two indicators, the UV-weighted melanoma rate and the
      melanoma-weighted UV level. A linear relationship was computed for the UV
      weighted melanoma incidence rate while an exponential decay simulated the
      melanoma-weighted UV level. The slope of the UV-weighted melanoma linear model
      was indicative of the mean cutaneous melanoma incidence rates attributed to solar
      UV exposures in the U.S. An excess (i.e., above the average) of cutaneous
      melanoma cases was observed in the northeast U.S. A deficit of cutaneous melanoma
      cases for the estimated UV levels was observed in Texas, Nevada, and Arizona and
      to a lesser extent in California and New Mexico.

PMID- 25985531
TI  - [Expression of the thermostable carboxypeptidase Taq gene in Pichia pastoris
      GS115].
AB  - To express recombinant carboxypeptidase from Thermus aquaticus (Cpase Taq) in
      Pichia pastosis, the open reading frame coding thermostable Cpase Taq was
      optimized based on the preference of P. pastoris codon usage and synthesized in
      vitro. The novel gene was cloned into P. pastoris expression vector pHBM905A and
      the sequence coding 6xHis tag was fused with the ORF of Cpase Taq gene. The
      recombinant plasmid was named pHBM905A-Cpase Taq and transformed into P. pastoris
      GS 115. Transformants were induced with 1% methanol for 72 h until the enzyme
      yield reached 0.1 mg/ml. The enzyme was purified and its enzymatic properties
      were analyzed. The results showed that the specific enzyme activity reached
      maximum at 75  degrees C and pH 7.5, which was about 80 U/mg. It was the first
      report about the secretory expression of Cpase Taq in P. pastoris GS115. Because
      of its large-scale preparation, this enzyme may be applied in industrial
      hydrolysis of peptides into amino acids in the future.

PMID- 25985534
TI  - Evaluation of ultraviolet germicidal irradiation in reducing the airborne
      cultural bacteria concentrations in an elementary school in the Midwestern United
      States.
AB  - This article describes a casestudythe authors conducted in an elementary school
      in the Midwest. The objective was to evaluate the performance of ultraviolet
      germicidal irradiation (UGVI) to reduce the bioaerosol concentration in a
      classroom. Two fourth grade classrooms with the same dimensions were studied. One
      classroom was designated as the UVGI group and the other as the control group.
      Two-stage Tisch culturable impactors were utilized for collecting airborne
      bacteria with monthly samples collected from October 2012 to January 2013.
      Nonparametric methods were applied and p-values smaller than .05 were deemed
      significant. The concentrations of airborne cultural bacteria with a smaller size
      (1-8 pm) and the total bacterial concentrations from the UVGI classroom were
      significantly lower than those of the control room in three of four sampling
      months. These results could provide the preliminary results necessary to
      determine the effectiveness of upper-room UVGI in reducing the concentration of
      airborne cultural bacteria in classrooms and other buildings.

PMID- 25985535
TI  - Fate and transport of enteric microbes from septic systems in a coastal
      watershed.
AB  - Onsite wastewater treatment systems (OWTS) are commonly used in coastal areas to
      treat household wastewater. These systems represent potential sources of fecal
      pollution of groundwater and nearby surface water. OWTS are expected to reduce
      microbial concentrations in wastewater; however, system and environmental factors
      can affect treatment efficiency and impacts on ground and surface water. In the
      study of OWTS described in this article, the authors sampled septic tanks and
      groundwater at two households in coastal North Carolina between October 2009 and
      October 2011. Samples were tested for the fecal indicator microbes E. coli,
      enterococci, and Clostridium perfringens. Microbial source tracking was also
      performed in year two. Results showed that enteric microbe concentrations in
      groundwater significantly decreased with distance from the OWTS. Human markers of
      fecal contamination were also detected in the OWTS and downgradient groundwater,
      indicating that OWTS can impact the microbial quality of shallow groundwater.

PMID- 25985536
TI  - It's all about the return on investment: the Model Aquatic Health Code.

PMID- 25985537
TI  - Biomonitoring and environmental public health tracking.

PMID- 25985538
TI  - 101 endangered jobs by 2030.

PMID- 25985539
TI  - What makes it work?

PMID- 25985540
TI  - Inter-observer reliability of the ankle-brachial index in a pediatric setting.
AB  - OBJECTIVE: The aim of our study was to determine the inter-observer reliability
      of the ankle-brachial index (ABI) in the pediatric population. This was done to
      determine if this simple diagnostic test could be utilized in lieu of CT
      angiograms to reduce radiation exposure to children sustaining trauma,
      particularly physeal fractures about the knee. DESIGN: Diagnostic study of
      consecutive patients with no applied "gold-standard" test. SETTING: Level I
      pediatric hospital. PATIENTS/PARTICIPANTS: Thirty consecutive patients from a
      busy fracture clinic were recruited. Patients ranged in age from 7-17 years.
      INTERVENTION: Manual systolic blood pressure measurements from uninjured limbs
      were taken by two independent attending orthopaedic surgeons from the ipsilateral
      brachial, dorsalis pedis, and posterior tibial arteries of each patient. MAIN
      OUTCOME MEASUREMENTS: The intraclass correlation coefficients from each anatomic
      area were calculated. RESULTS: Intraclass correlation of measurements from all
      three anatomic locations showed good inter-observer reliability. The intraclass
      correlation coefficients from the brachial, dorsalis pedis, and posterior tibial
      arteries were 0.699, 0.815, and 0.740, respectively. Therefore, the calculation
      of the ABI was consistent between the two observers despite any variability in
      individual pressure measurements. CONCLUSIONS: The ABI is a fast, non-invasive
      test that can be applied to the pediatric population in the evaluation of lower
      extremity arterial injury associated with orthopaedic trauma. It can obviate the
      need for tests such as CT angiograms that have inherent risks, particularly those
      associated with radiation exposure that are of concern in a young child.

PMID- 25985542
TI  - The changing face of patient care: delivering patient-centered and culturally
      competent care in an evolving world.

PMID- 25985541
TI  - Implementing a patient portal at the family medicine center.

PMID- 25985543
TI  - IHF and IAPO: Fostering patient engagement.

PMID- 25985544
TI  - Australia - Consumers Health Forum of Australia: Enabling health service
      consumers to have an active role throughout the health system.
AB  - Patients are recognized as active consumers within the Australian health care
      system which is a universal health care system funded nationally, with state
      level responsibility and local delivery. Patient engagement with hospitals is
      therefore focused on making services more patient-centred. As a national body
      representing the views of patients in Australia the Consumers Health Forum (CHF)
      helps affiliates to improve local and regional engagement. Initially, engagement
      was driven by local relationships with administrators and clinicians, whereas now
      there is more systematic patient representation on committees and boards -
      although local involvement can still be a challenge. Advocating for the
      application of national standards to different local contexts is ongoing and
      these are important because collecting, measuring and responding to patient views
      and involving them in decision-making can have a tangible impact on a hospital's
      "bottom-line" performance and funding.

PMID- 25985545
TI  - Hong Kong - The Hong Kong Alliance of Patients' Organizations: Working
      constructively to increase hospital openness and accountability.
AB  - The Hong Kong Alliance of Patients' Organizations (HI(APO) comprises 44
      affiliated patient groups who advocate across the region, improving patient
      experiences and increasing advocacy and awareness. Initially established to
      increase accountability to patients and representation in a changing health
      system, the Alliance has worked to expand patient input on local and territorial
      decision-making by partnering with individual hospitals and increasing links with
      the Hospital Authority Board. Patients are now represented on most committees
      affecting patient care and the delivery of health services, and more widely in
      health care policy decision-making. The Alliance advocates for patients as active
      and constructive consumers rather than passive recipients of services and lobbies
      for better representation and involvement in treatment decisions. It has also
      increased media exposure which has helped to grow representation so that patients
      are now present on all 11 Authority Committees and are asked for their views. The
      patient ambassadors programme offers training for patients to be representatives
      at ward level and within the local hospital committee; and by building
      constructive relationships over time with hospital partners, HKAPO affiliate
      organizations have been able to start making improvements in the training of
      professionals in hospitals and informing staff about patient engagement,
      advocating for new clinical interventions and a more patient-centred approach.

PMID- 25985546
TI  - The South African Depression and Anxiety Group and government hospital partners:
      Addressing the challenge of poor adherence in psychiatry.
AB  - The Helen Joseph Hospital, a government regional hospital in Johannesburg, South
      Africa, became aware of patient non-adherence issues at their specialist
      psychiatric outpatient department. In partnership with the South African
      Depression and Anxiety Group (SADAG), Africa's largest support network and
      advocacy group for people affected by mental health problems, and sponsored by
      Janssen Pharmaceuticals, they aimed to address the issue of non-adherence by
      developing and implementing a Reminder and Support Adherence Programme (RSAP). By
      providing a comprehensive service that regularly reminds patients to take their
      medication, attend their clinic appointments, offers free health information and
      psychosocial support, this has allowed many patients to benefit from the
      programme's ability to address the range of problems related to non-adherence.

PMID- 25985547
TI  - United States - The Leukemia & Lymphoma Society: Working with patients, carers
      and hospital professionals to improve awareness, treatment and patient choice.
AB  - By working locally with patients and carers from diagnosis and treatment through
      to aftercare, helping professionals to improve their knowledge and awareness
      about blood cancers and best practice treatment, while also advocating at the
      national level, the Leukemia & Lymphoma Society (LLS) is working to strengthen
      coordination between patients, carers and professionals along the whole care
      pathway. By helping patients to become more engaged and empowered to make
      informed choices, improve treatment for blood cancers through education, LLS is
      working to enhance patient-centred care in a largely privatized and fragmented
      health services system in the United States. By providing web-based resources and
      a free national helpline, alongside a face to face local support network, LLS is
      helping patients to learn more about their condition, treatment choices and the
      care pathways they can access. Free professional development and education
      seminars are also offered to nurses, oncologists and social workers in hospitals,
      highlighting new approaches to treatment and care with a patient-centred
      approach.

PMID- 25985548
TI  - The UNICANCER Patient Expectations Observatory: A new role for patients in health
      care institutions.
AB  - Recognizing the role played by patients in their own management, UNICANCER set up
      in November 2011 a unique initiative in France: the Patient Expectations
      Observatory. This was designed to reorient and improve the quality of care
      provided by comprehensive cancer centres in the UNICANCER group based on a better
      knowledge and understanding of patient perceptions and preferences. An innovative
      internet-based consultation process enabled us to record and prioritize patient
      expectations. Patient management improvement actions for cancer centres were then
      used to equitably satisfy the identified patient expectations. By using patients'
      own expectations of their health care, cancer centres can therefore provide an
      example of the new modalities of patient participation in health care
      institutions, in line with the changes proposed by public authorities.

PMID- 25985549
TI  - Patients as partners for improving safety.
AB  - Safety is a crucial aspect in any medical treatment. The awareness that patients
      can play an essential role in the prevention of errors and adverse events has
      increased over the last decade, connected to the movement for patient
      empowerment. Patients are no longer "objects" and "victims" of a treatment, but
      are alert observers and partners and become an active "last barrier" for the
      prevention of errors. This new role is challenging: for the patient as it
      requires action in a vulnerable period of dependence and the courage to intervene
      at the right moment; and for the caregivers who are facing a patient who is
      critical and dares to speak-up.

PMID- 25985550
TI  - The role of patients: Perspectives from a large, not-for-profit, tertiary care
      teaching hospital in the developing world.
AB  - Recent literature and studies show the significant role that patients and
      families can play during their transition through different points along the
      continuum of care. To date, our observation is that in our environment, patients
      and families input and engagement in the health care process has remained
      passive, with most of the decisions related to patient care being reserved for
      health care providers. Health care in many parts of the developing world still
      faces a similar challenge. This paper presents the initiatives of a large, not
      for-profit, tertiary care teaching hospital in Karachi, Pakistan, on planning and
      implementing some best evidence-based practices in re-shaping the role of
      patients and families with the goal of enhancing the quality of their care. It
      also points out the effect of local cultures in making the role of the patient
      and family in their care as beneficial as it can be to improve clinical outcomes
      and their quality of life. Additionally, factors such as literacy, education,
      socioeconomic class and the attitude of health care providers in underdeveloped
      countries requires a significant change for the effective involvement of patients
      in their own care.

PMID- 25985551
TI  - Dutch hospitals provide reliable "one click" patient information using a Quality
      Window.
AB  - In 2014, the Dutch Association of Hospitals (Nederlandse Vereniging van
      Ziekenhuizen, NVZ) launched the "Quality Window" at general hospitals across the
      Netherlands. The Quality Window is an online platform for patients which shares a
      hospital's current and previous scores on ten quality indicators, from patient
      experience to employee satisfaction. The Quality Window therefore responds to the
      growing demand for information and transparency when it comes to hospital care
      and performance. Not only can patients access helpful information about a
      hospital's quality through the Quality Window, they can also compare results with
      other hospitals, the national average, and more. Many hospitals also take the
      opportunity to expand on how indicators work in practice and the actions being
      taken towards improvement. The Quality Window was developed with the help of
      hospitals and patients. Over the coming years it will be expanded to university
      hospitals across the country. General hospitals will also begin developing
      Quality Windows for specific patient groups, such as cancer patients.

PMID- 25985552
TI  - Outlook for 2015.

PMID- 25985553
TI  - Breast centre certification in Europe.
AB  - Certification procedures help to improve the quality process by modifying
      organizational and clinical attitudes to the benefits of increased quality in the
      standards of care. It provides a critical attitude towards daily work and
      requests to dedicate sufficient time to multidisciplinary analysis on breast
      centre organization activity and performance. Breast Centres Certification
      (BCCERT) is a nonprofit association, operating in compliance with international
      standards on certification, which carries out voluntary certification of breast
      centres based on the requirements of the European Society of Breast Cancer
      Specialists (EUSOMA) and aims to improve and standardize the Level of patient
      care throughout Europe.

PMID- 25985554
TI  - The rehaVital Stroke Network: An integrated, post-discharge, patient care model
      initiated by durable medical equipment specialists.
AB  - Outpatient care for patients with chronic illnesses in Germany (e.g., stroke
      patients) is currently fragmented, with little interconnectivity among the
      different care providers. After being cared for in a highly structured inpatient
      environment, patients are often discharged alone with limited supportive care at
      home. With the goal of accompanying patients on their way back to autonomous
      mobility and social participation, rehaVital members developed an integrated care
      model. In this model, patients' perspectives and needs are recognized as central
      determinants in their post-discharge care. Further key features include
      structured interconnectivity among the various care providers with transparent
      treatment goals and progress demonstrated by quality indicators.

PMID- 25985555
TI  - The willingness of and barriers to Korean health care providers participating in
      a humanitarian assistance field hospital responding to an urgent global health
      crisis.
AB  - PURPOSE: As the number of disaster and humanitarian crisis increases, there is an
      emphasis on the prompt dispatching of humanitarian assistance field hospitals
      (HAFHs) in order to relieve a disaster-stricken society as soon as possible. The
      participants' individual motivation constitutes one of the most important factors
      in achieving successful HAFH activities. The aims of this study are to evaluate
      health care providers' willingness to participate in HAFHs when there is an
      urgent global health need and to examine their motives, perceived barriers, and
      concerns using a simulated global disaster scenario. RESULTS: Seventy health care
      providers completed a survey which asked about their willingness to join a HAFH
      that was being dispatched immediately. Forty-five of the 70 respondents (64.3%)
      answered that they were willing to join an HAFH, which departed within 24 hours
      of a hypothetical earthquake. The major perceived barriers to participation in an
      HAFH included "pre- scheduled work commitments in home institutions,"
      "insufficient support from home institutions," and "insufficient field safety and
      security". CONCLUSION: Policy-makers need to proactively establish support from
      the institutions that employ disaster-related health care providers, in order to
      secure their participation in HAFHs and to ensure optimal preparedness for global
      disaster relief activities.

PMID- 25985556
TI  - The well-being and mental health of male and female hospital doctors in Germany.
AB  - This study focuses on the associations between subjective well-being and mental
      health. In addition, gender differences are evaluated. The research was conducted
      as a cross-sectional online survey using a standardized questionnaire to assess
      physicians' mental health and well-being. Results have shown moderate scores for
      mental health and well-being in physicians. In general, male physicians perceive
      a better well-being and higher mental health score than female physicians. Well
      being and mental health should be improved to increase physicians' work ability
      and subsequently, the quality of treatment and patient satisfaction. Mental
      health prevention should be more widely implemented in hospitals, and its
      awareness and early treatment should be encouraged. Mental health interventions
      might include modifying physicians' daily work schedules, providing curricula on
      mental health and offering training on the awareness of distress and well-being.

PMID- 25985557
TI  - The effects of hospital reforms on the management of public hospitals in
      Tanzania: Challenges and lessons learnt.
AB  - Although hospital reforms are being advocated internationally as part of a
      solution to hospital management problems in developing countries, studies have
      shown that they do give rise to some challenges. A study was undertaken that used
      in-depth interviews, focus group discussion and document review to examine
      hospital reforms. The article examines the effects of reforms on the management
      of Level II public hospitals in Tanzania and documents the related challenges and
      lessons Learnt. It is shown that hospital reforms have mixed effects in resource
      strained hospitals, and that hospital reform actions may have replaced the
      bureaucratic inefficiencies associated with hospitals being managed from the
      central level (MoHSW) with the equally bureaucratic inefficiencies that
      characterize the management of these hospitals from a supposedly local level, the
      office of the Regional Administrative Secretary (RAS). Managing hospitals from
      this level seems to cause many hospital management problems to be left
      unattended.

PMID- 25985558
TI  - Patient safety initiatives in Germany: The hospital perspective.
AB  - Patient safety has become a major focus in German socio-political awareness over
      the past decade. Efforts to improve patient safety have been increased nationwide
      and involve all stakeholders in the German health care system. The government
      aims to improve the quality of health care services both in the hospital and in
      the ambulatory care sector with a quality campaign. On one hand it strengthens
      patients' power and participation in decision-making and on the other hand it
      stresses the need for health care providers themselves to enhance patient safety
      and to ensure the nationwide provision of excellent health care, whereby
      hospitals play a vital role in providing a comprehensive system of locally
      available clinical treatment. This article focuses particularly on the numerous
      mandatory and voluntary initiatives provided by hospitals with respect to quality
      of care and patient safety, however further information about the context can be
      found in the online version cited in the footnote below.

PMID- 25985559
TI  - The Apollo Accreditation Program: A web-based Joint Commission International
      standards compliance management tool.
AB  - Creating and implementing processes to deliver quality care in compliance with
      accreditation standards is a challenging task but even more daunting is
      sustaining these processes and systems. There is need for frequent monitoring of
      the gap between the expected level of care and the level of care actually
      delivered so as to achieve consistent level of care. The Apollo Accreditation
      Program (AAP) was implemented as a web-based single measurable dashboard to
      display, measure and compare compliance levels for established standards of care
      in JCI accredited hospitals every quarter and resulted in an overall 15.5%
      improvement in compliance levels over one year.

PMID- 25985560
TI  - Environmental pollution: An enormous and invisible burden on health systems in
      low- and middle-income counties.
AB  - Background. Environmental pollution has become the leading risk factor for death
      in low- and middle-income countries (LMICs). The World Health Organization and
      others calculate that exposures to polluted air - indoor and outdoor, water and
      soil resulted in 8.4 million deaths in LMICs in 2012. By comparison, HIV/AIDS
      causes 1.5 million deaths per year, and malaria and tuberculosis Less than 1
      million each. The diseases caused by pollution include the traditional scourges
      of pneumonia and diarrhea, but increasingly they also include chronic, non
      communicable diseases (NCDs) such as such as heart disease, stroke and cancer.
      Method. We review the diseases caused by pollution and the multiple economic and
      human burdens that these diseases impose on health systems in countries with
      already limited resources. Results. We find that diseases caused by pollution
      increase health care costs, especially for high-cost NCDs. They impose an
      unnecessary load on health care delivery systems by increasing hospital staffing
      needs and thus diverting resources from essential prevention programmes such as
      childhood immunizations, infection control and maternal and child health. They
      undermine the development of poor countries by reducing the health, intelligence
      and economic productivity of entire generations. Pollution is highly preventable
      and pollution prevention is highly cost-effective. Yet despite their high
      economic and human costs and amenability to prevention, the diseases caused by
      pollution have not received the attention that they deserve in policy planning or
      in the international development agenda. Conclusion. Pollution is not inevitable.
      It is a problem that can be solved in our lifetime. Given the great impact of
      pollution on health and health care resources and the high cost-benefit ratio of
      pollution prevention, efforts to mitigate pollution should become a key strategic
      priority for international funders and for governments of LMICs. Recommendation.
      Assisting LMICs to prioritize disease prevention through the management of
      pollution is a highly cost-effective strategy for enhancing population health,
      reducing the burden on limited health resources and advancing national
      development.

PMID- 25985561
TI  - Chinese herbal medicine for carriers of the hepatitis B virus: an updated
      systematic review and meta-analysis.
AB  - More than a third of the world's population is infected with the hepatitis B
      virus (HBV) and 5% are thought to be HBV carriers, putting them at risk of
      developing serious liver diseases. The treatment of liver diseases with Chinese
      herbal medicines (CHM) dates back 2,500 years and the aim of this analysis was to
      evaluate the efficacy and safety of CHM for HBV carriers compared to Western
      medicine (WM) or placebo and to summarize the most commonly used herbs. Several
      databases, such as Pubmed, Embase and the Chinese database CNKI, were used to
      evaluate randomized, controlled trials (RCTs) focused on CHM treatment for HBV
      carriers up to 2013. We performed a systematic review and meta-analysis on the
      herbs and their effect on hepatitis B viral proteins (HBeAg, HBsAg) and HBV DNA.
      Subgroups were examined based on the study design and pooled risk ratios (RRs)
      were estimated with 95% confidence intervals (CIs). For the meta-analysis, we
      focused on 11 out of 52 RCTs (Jadad >= 2) and found that CHM was more effective
      than placebo for HBeAg seroconversion when combined with WM (RR 4.67, 95% CI 1.36
      15.98; P = 0.01; P = 39%); Radix Astragali was the most commonly used herb. Those
      that received CHM were more prone to adverse events; however, they were mild and
      reversible. The risk of bias was assessed with regards to blinding, incomplete
      outcome data and publication bias. It should be noted that, due to the poor
      methodological quality of the studies and the small number of RCTs, the results
      cannot fully support the use of CHM in the treatment of HBV carriers. To
      conclude, CHM may be used to treat HBV carriers, but rigorously designed RCTs
      with long-term follow-ups are required to further evaluate the benefits and
      safety of CHM.

PMID- 25985562
TI  - Synthesis and structure elucidation of 2,3,5,6,7,8-hexahydro-1 H
      [1,2,4]triazolo[1,2-a]pyridazine-1-thione, 3,3-disubstituted and 2-substituted
      derivatives and evaluation of their inhibitory activity against inducible nitric
      oxide synthase.
AB  - The 3-monosubstituted 2,3,5,6,7,8-hexahydro-1 H-[1,2,4]triazolo[1,2-a]pyridazine
      1-thiones 3 (R1, R3 = H) were recently reported to possess inhibitory activity
      against inducible nitric oxide synthase in a cell based assay (Schulz et al.
      2013). The 3,3-disubstituted 2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2
      a]pyridazine-1-thiones 3 and 4 (R2,R3 ? H) were synthesized by cyclocondensation
      of the hexahydropyridazine-1-carbothioamides 1 with ketones. In order to access
      the 3,3-unsubstituted 2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1
      thiones, the unsubstituted parent system of these compounds, several synthetic
      routes were studied. By these methods the desired heterocyclic system 2a as well
      as new a-anellated and N-substutited hexahydropyridazines were obtained. The
      biological evaluation of the title compounds confirmed the previously made
      finding that an aromatic moiety in position 3 of the substance is important for
      an inducible nitric oxide synthase (iNOS) inhibitory activity.

PMID- 25985563
TI  - Impact of pharmaceutical excipients on in vitro association of saquinavir to
      chylomicrons.
AB  - This study was performed to investigate the impact of pharmaceutical excipients
      commonly used for lymphatic transport on in vitro drug association with
      chylomicrons (CM). A CM association study was conducted using saquinavir
      solubilized in four different pharmaceutical excipients. We observed a linear
      relationship between saquinavir solubility and drug association, suggesting that
      the solubility of saquinavir in excipients is a key determinant for successful
      lymphatic delivery. Broadly, these results suggest that excipients with good
      solubilization properties may be advantageous for enhancing lymphatic drug
      delivery.

PMID- 25985564
TI  - A novel zwitterionic inhibitor of aldose reductase interferes with polyol pathway
      in ex vivo and in vivo models of diabetic complications.
AB  - Recently a zwitterionic principle has been suggested as an alternative to
      bioisosteric replacement for increasing low bioavailability of aldose reductase
      inhibitors bearing an acidic function. In the present work we studied the effect
      of a novel zwitterionic inhibitor of aldose reductase [(2-benzyl-2,3,4,5
      tetrahydro-1 H-pyrido[4,3-b]indole-8-yl)-acetic acid, compound 1] on sorbitol
      accumulation in ex vivo and in vivo models of diabetic complications. The effect
      of 1 on sorbitol accumulation in isolated rat eye lenses incubated with high
      glucose and in selected organs of streptozotocin-induced diabetic rats was
      evaluated. Significantly increased sorbitol levels were recorded in the lenses
      incubated with 50 mM glucose in comparison with controls. Sorbitol production was
      inhibited by 1 at concentrations of 25 and 100 MUM. Under in vivo conditions in
      diabetic rats, significant elevation of sorbitol levels in selected organs was
      recorded. Compound 1 administered i.g. for five consecutive days (twice a day 25
      mg/kg) inhibited sorbitol accumulation in erythrocytes and the sciatic nerve, yet
      it was without effect in eye lenses. A similar picture of inhibition was observed
      after i.p. administration of 1. To conclude, the results suggest that the
      zwitterionic principle may represent a practicable way of improving
      bioavailability of aldose reductase inhibitors bearing an acidic function.

PMID- 25985565
TI  - Dihydroartemisinin exhibits anti-glioma stem cell activity through inhibiting p
      AKT and activating caspase-3.
AB  - Glioma stem cells (GSCs) have been proven to play key roles in tumorigenesis,
      metastasis and recurrence. Although dihydroartemisinin (DHA), a derivative of the
      antimalaria drug artemisinin, has been shown to have anti-cancer activity, it is
      still unclear whether DHA affects GSCs. This study investigated the effects of
      DHA on the growth and apoptosis of GSCs, as well as the possible molecular
      mechanism involved in these processes. GSCs were enriched using a non-adhesive
      culture system with serum-free neural stem cell medium. Their stemness
      characteristics were identified by assessment of tumor sphere formation, mRNA
      expression analysis, and immunofluorescence staining of stem cell markers (CD133,
      SOX2, and nestin). We found that DHA not only inhibited proliferation, which was
      determined with the cell counting kit-8 (CCK8) assay, but also induced apoptosis
      of GSCs, as evaluated with the annexin-V/PI flowcytometric assay. Interestingly,
      DHA treatment also induced a concentration-dependent cell cycle arrest in the G1
      phase according to the cell cycle assay. To reveal the underlying mechanisms, we
      detected the expression levels of p-Akt and Cleaved Caspase-3. The data showed
      that Cleaved Caspase-3 increased significantly in a dose-dependent manner (p <
      0.05) after the GSCs sphere cells were treated with 20, 40, and 80 MUM of DHA for
      24 h, which correlated with significantly decreased expression levels of p-Akt (p
      < 0.05). These data indicate that DHA selectively inhibits proliferation and
      induces apoptosis of GSCs through the down-regulation of Akt phosphorylation,
      which is followed by Caspase-3 activation, and these findings offer a new
      approach for treating gliomas.

PMID- 25985566
TI  - Combination of oxaliplatin and S-1 versus sorafenib alone in patients with
      advanced hepatocellular carcinoma.
AB  - Sorafenib and conventional systemic cytotoxicity chemotherapy are currently being
      used in parallel for the patients with advanced hepatocellular carcinoma (HCC).
      While sorafenib has been proven to improve the prognosis in patients with this
      malignant disease, however, the outcome of other newly developed systemic
      chemotherapeutic regimens remains controversial. We evaluated the outcome and
      safety of patients treated with the SOX regimen (oxaliplatin + S-1) and those
      treated with sorafenib in a single-center cohort. This retrospective study
      involved a total of 46 patients with advanced HCC, 22 of which were treated with
      SOX regimen (oxaliplatin [130 mg/m2] on day 1 and S-1 [80 mg/m2/day] on day 1-14,
      every 3 weeks), and 24 were daily treated with sorafenib (400 mg, b.i.d.). The
      median progression-free survival was 3.6 months (95% confidence interval [CI],
      1.7 to 5.6) with SOX and 1.7 months (95% CI, 1.5 to 1.9) with sorafenib,
      respectively (P = 0.444). The median overall survival in SOX and sorafenib group
      was 7.6 months (95% CI, 4.3 to 10.9) and 4.7 months (95% CI, 2.7 to 7.3),
      respectively (P = 0.246). Response rate was 22.2% with SOX and 5.6% with
      sorafenib, respectively (P = 0.154). The frequent side effects in SOX-treated
      patients were thrombocytopenia, elevation of transaminase levels and neuropathy,
      whereas hand-foot syndrome, diarrhea and pruritus were common in sorafenib
      treated patients. These preliminary results suggest that the SOX regimen may
      serve as an effective treatment for patients with advanced HCC, and the treatment
      related toxicities were generally well-tolerated.

PMID- 25985567
TI  - The association of ABCC3 promoter methylation with clopidogrel response in
      Chinese ischemic stroke patients.
AB  - Multidrug resistance protein 3 (MRP3), encoded by ABCC3, is an ATP-dependent
      efflux pump mediating the transport of many drugs, implicated in clopidogrel
      resistance. This study enrolled 87 ischemic stroke patients with CYP2C1 9*1/*1
      genotype, who received clopidogrel (75 mg/day) for at least 5 days before
      discharge. The maximum platelet aggregation (MPA) was measured by light
      transmittance aggregometry (LTA) to assess platelet function. Whole blood samples
      were obtained to evaluate the ABCC3 promoter methylation and mRNA expression of
      ABCC3. Pyrosequencing was carried out to investigate ABCC3 methylation and ABCC3
      mRNA expression was evaluated by qPCR. The ABCC3 methylation was neither
      significantly different among the four MPA quartile groups (P = 0.275) nor
      independently associated with MPA values (R = 0.100, P = 0.358). However, the
      ABCC3 promoter methylation status in 87 clinical samples from patients correlated
      inversely with the expression of ABCC3 (R = - 0.854, P < 0.001). In addition, the
      ABCC3 expression was neither significantly different among the four quartile
      groups (P = 0.499) nor independently associated with MPA values (R = 0.060, P =
      0.582). ABCC3 promoter methylation does not seem to exhibit any impact on MPA and
      clopidogrel response at all.

PMID- 25985568
TI  - Cardiovascular protective effects of IL-1 ra-Fc-IL-18BP on experimental
      myocardial infarction by inhibiting oxidative stress and inflammation in a rat
      model.
AB  - In this study, we examined the cardiovascular protective effects of IL-1ra-Fc-IL
      18BP on experimental myocardial infarction in a rat model. An animal model of
      myocardial infarction (MI) was induced by permanent ligation of the left anterior
      descending coronary artery (LAD) in SD rats. After surgery sixty male rats and
      sixty female rats were randomly divided into groups as followed: sham group, MI
      group, IL-1ra-Fc-IL-18BP 50,100, 200 mg/kg treatment groups, and verapamil 5
      mg/kg treatment group. IL-1 ra-Fc-IL-18BP and verapamil were administered to the
      animals immediately after operation by intravenous injection. Treatment with IL
      1ra-Fc-IL-18BP (50, 100 and 200 mg/kg) could remarkably decrease infarct size
      from 24.82% to 13.43% (p < 0.05), and decrease the activities of serum aspartate
      aminotransferase (AST), creatine phosphokinase (CPK) and lactate dehydrogenase
      (LDH) compared with sham group (p < 0.05). Meanwhile, treatment with IL-1ra-Fc-IL
      18BP (200 mg/kg) could significantly increase the activities of superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), but decreased the content of
      malondiadehyde (MDA) in serum (p < 0.05). Furthermore, IL-1ra-Fc-IL-18BP
      marablely reduced the content of calcium (Ca2+) in serum (p < 0.05), and also
      decreased the levels of serum interleukin-1beta (IL-1beta), tumor necrosis factor
      (TNF-alpha) (p < 0.05). Histopathological results demonstrated the same
      protective effect of IL-1ra-Fc-IL-18BP All these results above indicated that IL
      1ra-Fc-IL-18BP has protective effects in myocardial infarction, improves free
      radicals metabolism, ameliorates myocardial calcium overload and inhibits the
      release of inflammatory cytokines.

PMID- 25985569
TI  - The effect of Na+/taurocholate cotransporting polypeptide (NTCP) c.800C > T
      polymorphism on rosuvastatin pharmacokinetics in Chinese healthy males.
AB  - This study was designed to investigate the potential association between NTCP
      c.800C >T polymorphism and rosuvastatin pharmacokinetics in Chinese healthy
      males. 305 individuals were enrolled to identify NTCP c.800C > T, OATP1B1 c.521T
      > C and BCRP c.421C > A genotypes by direct sequencing and pyrosequencing
      methods, respectively. 17 healthy volunteers who were OATP1B1 c.521TT and BCRP
      c.421CC wild-type homozygotes with different NTCP c.800C > T genotype were
      selected to participate in this pharmacokinetic study. Nine were NTCP c.800CC
      wild-type homozygotes and the other eight subjects were carriers with at least
      one c.800T variant allele (seven subjects with c.800CT genotype and one was
      homozygote of c.800TT). All the subjects received a single oral dose of 10 mg
      rosuvastatin. The plasma concentrations of rosuvastatin were measured up to 72 h
      by a LC-MS method. NTCP c.800C > T genetic polymorphism markedly effected
      rosuvastatin pharmacokinetics. The AUC(o-72) and AUC(0 --> infinity) in subjects
      with NTCP c.800CT + TT genotype were 56% (162.64 +/- 37.55 vs. 103.99 +/- 28.15
      ng x h/ml, P = 0.016) and 57% greater (178.51 +/- 42.75 vs. 113.60 +/- 33.73 ng x
      h/ml, P = 0.020) than those in the c.800CC wild-type subjects, respectively. In
      the c.800CT + TT mutant group, the C(max) was about 78% higher than those in
      c.800CC genotype (14.31 +/- 3.63 vs. 8.04 +/- 1.72 ng x h/ml, P = 0.004). The
      oral clearance (CL/F) of rosuvastatin in subjects with the c.800CT+TT genotype
      was only 63% of those in the c.800CC genotype (58.32 +/- 12.16 vs. 93.04 +/-
      20.61 ng x h/ml, P = 0.009). The half-time (T1/2) and the T(max) had no
      significant difference between two groups (p = 0.466 and 0.713, respectively).
      NTCP c.800C > T polymorphism play a critical role in the individual variability
      of rosuvastatin pharmacokinetics in Chinese healthy males after excluding the
      impact of OATP1B1 c.521T > C and BCRP c.421C > A polymorphisms.

PMID- 25985570
TI  - Pharmacists Adolf Schall and Ernst Ratzlaff and the synthesis of tabun-like
      compounds: a brief history.
AB  - The history of the synthesis of organophosphate inhibitors of cholinesterase
      starting with the synthesis of tetraethyl-pyrophosphate by Moschnin(e) and de
      Clermont and leading to the recognition about half a century later of the
      toxicity of the phosphor ester by Lange and von Krueger has been told in great
      detail previously. An almost parallel history -described originally by Bo
      Holmstedt--exists for organophosphonate inhibitors of cholinesterase starting
      with the synthesis (1898) in Rostock of diethylamido-ethoxy-phosphoryl-cyanide by
      the pharmacist Adolph Schall (1870-1957), a graduate student of August Michaelis
      (1847-1916), the re-examination of the chemical structure of the Schall compound
      (1903) by Michaelis, recognition (1937) of the toxicity of class by Gerhard
      Schrader (1903-1990) and confirmation (1951) of the structure by Bo Holmstedt
      (1919-2002). This short report attempts to shed some light on the life of the
      pharmacists and chemists involved in the synthesis of the first P-CN
      organophosphonate inhibitor of cholinesterase, focusing on the two less known
      pharmacists, the graduate students of Professor Michaelis Adolph Schall and Ernst
      Ratzlaff (1870-1948).

PMID- 25985571
TI  - Microdialysis as a tool to determine the skin concentration of mometason furoate
      in rats.
AB  - The objective of this study was to investigate the feasibility of microdialysis
      as a tool to determine the skin concentration of mometason furoate (MF), a
      lipophilic and highly protein-bound compound. The relative recovery (RR) of
      mometasone furoate was determined by an in vitro no-net-flux method using three
      different perfusates (40% PEG400, 5% fat emulsion, and 20% fat emulsion) and four
      flow rates (0.5, 1, 2, and 4 MUL x min(-1)). With the increasing of flow rate,
      the relative recovery was decreased from 48.8% to 3.1%. The in vitro recovery was
      increased to 23.71%, 42.76% and 56.21% when 40% PEG400, 5% fat emulsion or 20%
      fat emulsion was used as microdialysis perfusates, respectively. Fat emulsion
      (5%) was chosen as the perfusate to evaluate the in vivo recovery by a
      retrodialysis method, in which mometasone furoate concentration in different
      tissues was determined. The result showed that concentrations of mometasone
      furoate in the dermis was greater than that in the subcutaneous or muscle tissue.
      It was concluded that a recovery enhancer could be used in microdialysis
      technique, especially for determining skin concentrations of lipophilic and high
      protein-bounds.

PMID- 25985572
TI  - Effective mucoadhesive water-soluble polymers for the solidification
      transformation of phospholipid-bile salts-mixed micelles.
AB  - Cucurbitacin B (Cu B), formulated in the phospholipid-bile salts-mixed micelles
      (PL-BS-MMs), was transformed into dry powders by solidification process.
      Solidification methods for this transformation included freeze-drying, spray
      drying or vacuum-drying, and different grades of process parameters called
      conservative, moderate and aggressive have been used in each solidification
      method, respectively. Saccharides (mannose, trehalose and glucose), polyethylene
      glycol (PEG) and mucoadhesive water-soluble polymers (carrageenan,
      hydroxpropylmethylcellulose (HPMC) and gelatin) were selected as the stabilizer,
      respectively. The influence of different stabilizers on the redispersibility of
      solid Cu B-PL/SDC-MMs was systemically investigated, such as the redispersibility
      index (RDI). The results showed that there were significant differences in RDI
      from samples stabilized by different stabilizers. The solid Cu B-PL/SDC-MMs
      stabilized by mucoadhesive water-soluble polymers (carrageenan, HPMC and gelatin)
      have better redispersibility under different solidification approaches, compared
      with those samples stabilized by other stabilizers. The results indicated that
      the mucoadhesive water-soluble polymers could effectively counter various
      stresses from the solidification process and prevent the nanocrystal surface from
      agglomeration. The combined action between steric hindrance and increased
      viscosity appeared to effectively avoid irreversible particle aggregation.

PMID- 25985573
TI  - Potential inhibitory effect of herbal medicines on rat hepatic cytochrome P450 2D
      gene expression and metabolic activity.
AB  - The aim of current study was to investigate the effect of some commonly used
      medicinal herbs on the regulation of rat CYP2D gene expression and its metabolic
      activity. Wistar albino rats were treated for seven consecutive days with
      selected doses of five commonly used herbs (Trigonella foenum-graecum, Ferula
      asafoetida, Nigella sativa, Commiphora myrrha and Lepidium sativum). Thereafter,
      rat livers were harvested and CYP2D mRNA levels were determined by RT-PCR. The
      metabolic activity of CYP2D was performed on rat hepatic microsomes using
      dextromethorphan as specific substrate. All investigated herbs produced
      inhibition of CYP2D mRNA expression and metabolic activity. The inhibitory
      potential of investigated herbs on rat CYP2D mRNA was in the following order:
      Commiphora myrrha > Nigella sativa > Lepidium sativum > Trigonella foenum-graecum
      > Ferula asafoetida. Whereas, the inhibitory potential of investigated herbs on
      CYP2D mediated enzyme metabolic activity was found in following order: Nigella
      sativa > Lepidium sativum > Trigonella foenum-graecum > Commiphora myrrha >
      Ferula asafoetida. The current study shows that only used herbs reduce CYP2D
      activity in rat liver microsomes at the transcriptional levels. Such effects
      could lead to undesirable pharmacological effects of clinically used low
      therapeutic index CYP2D substrate drugs.

PMID- 25985574
TI  - Activation of G-protein-coupled receptor 30 increases T-type calcium currents in
      trigeminal ganglion neurons via the cholera toxin-sensitive protein kinase A
      pathway.
AB  - G protein-coupled receptor 30 (GPR30) is a seven transmembrane domain G protein
      coupled receptor. In our study, GPR30 expression was found in trigeminal ganglia
      (TG) in mice, detected by RT-PCR and western blotting. We examined the effects of
      GPR30 activation on T-type calcium channels using GPR30-specific compound 1 (G
      1), a GPR30-selective agonist, in TG neurons and demonstrated that G-1 induced an
      increase in T-type calcium channel currents (T-currents) in TGs. Intracellular
      infusion of GDP-beta-S and pre-treatment of the neurons with cholera toxin (CTX)
      blocked the effects of G-1, suggesting that the G(s)-protein was involved.
      Intracellular application of the protein kinase A (PKA) inhibitor PKI 6-22 or
      pretreatment of the neurons with H89 abolished G-1 -induced enhancement of T
      currents in TG neurons. However, incubation with PKC inhibitor elicited no such
      effects. In conclusion, our study shows that activation of GPR30 by G-1 increases
      T-currents via the CTX-sensitive and PKA-dependent pathway.

PMID- 25985575
TI  - Lentiviral vector mediated expression of Bax and hepatocyte growth factor
      inhibits vein graft thickening in a rabbit vein graft model.
AB  - Vein graft failure caused by vein graft thickening of the arterialized vein after
      bypass surgery is a main problem in clinical vascular surgery. Gene therapy is
      increasingly being recognized as a relevant treatment option for vein graft
      failure. In this study, we aimed to develop a novel recombinant lentivirus for
      the delivery of hepatocyte growth factor (HGF) and Bax in a rabbit vein graft
      model of bypass grafting. A bypass model was made in rabbits using the right
      jugular vein interposed end-to-end to the ipsilateral carotid artery. A
      lentivirus vector harboring HGF and Bax cDNAs (Lenti-HGF-Bax) was constructed and
      transduced into the venous grafts. Vein grafts were stained with hematoxilyn and
      eosin, and Masson. HGF and Bax expression in vein grafts was detected by
      immunohistochemical and Western blot analysis. Our results showed that vein graft
      thickening was reduced by 47.2 +/- 7.4% in lenti-HGF-Bax treated rabbits,
      compared to controls. Meanwhile, the ratio of intima/media area was reduced in
      lentil-HGF-Bax treated rabbits, compared to controls. The number of HGF and Bax
      positive cells was increased in vein grafts from rabbits treated by lenti-HGF
      Bax, compared to those from controls. Furthermore, protein levels of HGF and Bax
      were both significantly increased in grafts derived from rabbits treated by lenti
      HGF-Bax, compared to those from control. In conclusion, Lenti-HGF-Bax inhibits
      vein graft thickening in vein grafts and is a promising agent for preventing vein
      graft failure.

PMID- 25985576
TI  - Association of the use of amlodipine with clopidogrel response in Chinese
      patients undergoing percutaneous coronary intervention.
AB  - Until recently, the precise mechanism of clopidogrel resistance remains unclear.
      Some clinical studies have demonstrated that calcium channel blockers (CCBs)
      could reduce the antiplatelet effect of clopidogrel in white or black subjects,
      implicating in clopidogrel resistance. However, that remains to be determined in
      Chinese patients. In this study, we sought to determine whether there could be a
      decreased antiplatelet effect of clopidogrel and an increased risk for developing
      adverse cardiovascular events after concomitant use of different CCBs and
      clopidogrel in Chinese patients treated with percutaneous coronary intervention
      (PCI). A subcohort of 249 patients not carrying the CYP2C19 *2, *3 or *17 variant
      was identified from a total of 617 consecutive clopidogrel-treated patients
      undergoing PCI and then categorized into three groups according to various CCB
      treatments. Baseline data, clinical characteristics and blood samples were
      collected for all patients. The maximum platelet aggregation (MPA) was measured
      by light transmittance aggregometry (LTA) to assess the platelet function in
      blood samples obtained from patients on day 3 after starting daily clopidogrel
      maintenance doses. The primary clinical end-point was a definite stent thrombosis
      (ST) episode, whereas secondary end-points were other major adverse
      cardiovascular events within 12 months after stenting. Of the 249 patients not
      carrying CYP2C19 *2, *3 and *17 variants, the ADP-induced MPA differed
      significantly among the three groups (P < 0.001). The MPA values were 1.76 times
      in the amlodipine group (41.6 +/- 23.0%) than in the No CCB group (23.7 +/-
      14.1%) (P < 0.001). Moreover, in a linear regression model, the use of amlodipine
      was independently associated with MPA values (R = 0.375, P < 0.001), suggesting
      that the use of amlodipine might link to the increased MPA. However, the
      incidence of 1-year ST was not significantly higher in the amlodipine group than
      the No CCB group (OR, 4.80; 95% CI, 0.87 to 26.52; P = 0.068), and none of the
      risks for other adverse cardiovascular events were significantly different across
      the three groups (P = 0.11).

PMID- 25985577
TI  - Ginsenoside Rg3 inhibits lipopolysaccharide-induced adhesion molecule expression
      in human umbilical vein endothelial cell and C57BL/6 mice.
AB  - Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1
      (VCAM-1), P- and E-selectin play a key role for initiation of vascular
      inflammation. Ginsenoside, a class of steroid glycosides, is abundant in Panax
      ginseng root, which has been used for health promotion in Korea. In this study,
      we investigated the mechanism by which ginsenoside Rg3 may inhibit ICAM-1 and
      VCAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical
      vein endothelial cell (HUVEC) and C57BL/6 mice. LPS increased ICAM-1 and VCAM-1
      expression. Ginsenoside Rg3 prevented LPS-mediated increase of ICAM-1 and VCAM-1
      expression. LPS induced IkappaBalpha (IkappaBalpha) degradation within 1 hr.
      Ginsenoside Rg3 prevented the IkappaBalpha degradation stimulated with LPS.
      Moreover, ginsenoside Rg3 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC,
      in a concentration-dependent manner. In C57BL/6 mice, injection of LPS increased
      aortic ICAM-1 and VCAM-1 expression, which was prevented by ginsenoside Rg3.
      These data provide a novel mechanism where the ginsenoside Rg3 may provide direct
      vascular benefits with inhibition of leukocyte adhesion into vascular wall
      thereby providing prevention against vascular inflammatory disease.

PMID- 25985578
TI  - Modulation of P-glycoprotein function and multidrug resistance in cancer cells by
      Thai plant extracts.
AB  - The effects of ethanol extracts from Thai plants belonging to the families of
      Annonaceae, Rutaceae, and Zingiberaceae on P-glycoprotein (P-gp) function and
      multidrug resistance were examined in paclitaxel-resistant HepG2 (PR-HepG2)
      cells. All the extracts tested, significantly increased the accumulation of
      [3H]paclitaxel, a P-gp substrate, in the cells. Among nine extracts, Z01 and Z02,
      extracts from Curcuma comosa and Kaempferia marginata (Zingiberaceae family),
      respectively, potently increased the accumulation. In addition, Z01 and Z02
      increased the accumulation of other P-gp substrates, rhodamine 123 and
      doxorubicin, in PR-HepG2 cells in a concentration-dependent manner. Increased
      accumulation of rhodamine 123 and doxorubicin by Z01 and Z02 was also confirmed
      by confocal laser scanning microscopy. The effect of Z01 and Z02 pretreatment on
      the expression of MDR1 mRNA was also examined. The expression of MDR1 mRNA was
      not affected by the treatment of PR-HepG2 cells with these extracts for 48 hours.
      Cytotoxicity of paclitaxel was examined by XTT and protein assays in the absence
      and presence of Z02. Z02 potentiated the cytotoxicity of paclitaxel in PR-HepG2
      cells. These results suggest that Curcuma comosa and Kaempferia marginata
      belonging to Zingiberaceae are useful sources to search for new P-gp modulator(s)
      that can be used to overcome multidrug resistance of cancer cells.

PMID- 25985579
TI  - In vitro glucuronidation of propofol in microsomal fractions from human liver,
      intestine and kidney: tissue distribution and physiological role of UGT1A9.
AB  - Propofol (2,6-diisopropylphenol) is intravenously administered for anesthetic
      induction and maintenance, and is rapidly metabolized into its glucuronide,
      mainly by UDP-glucuronosyltransferase 1A9 (UGT1A9). In this study, propofol
      glucuronidation by liver microsomes (HLM), intestinal microsomes (HIM) and kidney
      microsomes (HKM) of humans were examined. The expression of UGT1A9 protein in
      HLM, HIM and HKM was analyzed by immunoblotting. The staining band intensities
      for UGT1A9 of HIM and HKM were 12% and 119% those of HLM, respectively. The
      kinetics of propofol glucuronidation by HLM and HKM exhibited substrate
      inhibition, whereas the kinetics by HIM followed the Michaelis-Menten model. The
      K(m), V(max) and CL(int) values of HLM were 41.8 MUM, 5.21 nmol/min/mg protein
      and 126 MUl/min/mg protein, respectively. The K(m) value of HIM was significantly
      higher (6.7-fold) than that of HLM, and the V(max) and CL(int) values were
      significantly lower (56% and 8.3%, respectively) than those of HLM. The K(m)
      value of HKM was comparable to that of HLM, and the V(max) and CL(int) values
      were significantly higher (2.1- and 3.7-fold, respectively) than those of HLM,
      respectively. These findings suggest that UGT1A9 expressed in the kidney as well
      as in the liver plays an important role in propofol glucuronidation. The
      information gained in this study should contribute to an appropriate use of drugs
      metabolized by UGT1A9.

PMID- 25985580
TI  - Endogenous BNP attenuates cardiomyocyte hypertrophy induced by Ang II via p38
      MAPK/Smad signaling.
AB  - Previous studies suggest that B-type natriuretic peptide (BNP) exerts inhibitory
      effects on cardiac hypertrophy. Our studies have shown that long-term treatment
      of rats with BNP attenuated cardiac hypertrophy via down-regulation of TGF-beta1
      and up-regulation of smad7. However, the mechanisms have not been fully
      elucidated. In the present study, we examined the role of endogenous BNP on
      cardiomyocyte hypertrophy and the related molecular mechanisms. Cardiomyocytes
      from neonatal rats were cultured and a cardiomyocyte hypertrophy model was
      established with angiotensin II (Ang II). The effects of blockade of endogenous
      BNP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated.
      Cardiomyocyte hypertrophy indices, including cell surface area, protein content
      and [3H] incorporation were measured. Smad and mitogen-activated protein kinase
      (MAPK) protein expressions were detected using Western blot analysis. We found
      that HS-142-1 increased Ang II-stimulated cardiomyocyte hypertrophy and Smad
      activation. In addition, the increase of cardiomyocyte hypertrophy and the
      activation of Smad caused by HS-142-1 were not altered by the ERK inhibitor,
      PD98059, but were decreased by the p38 MAPK inhibitor, SB203580. These results
      demonstrate that endogenous BNP attenuates cardiomyocyte hypertrophy, and this
      may be mediated through p38 MAPK/Smad, but not ERK/Smad signaling pathway.

PMID- 25985581
TI  - Decade-long use of the antimicrobial peptide combination tyrothricin does not
      pose a major risk of acquired resistance with gram-positive bacteria and Candida
      spp.
AB  - Tyrothricin, an antimicrobial peptide combination produced by Bacillus brevis
      consisting of gramicidins and tyrocidins commands broad antimicrobial activity
      against gram-positive bacteria and some yeasts in vitro. The polypeptide and its
      components have been used therapeutically for about 60 years in the local
      treatment of infected skin and infected oro-pharyngeal mucous membranes. Though
      older studies suggest that resistance development of originally susceptible
      microorganisms towards tyrothricin is a rare event, data concerning recent state
      of resistance are lacking. In the present in vitro study the susceptibility to
      tyrothricin of clinical isolates of bacterial and yeast origin from superficial
      swabs of the skin and mucous membranes of outpatients and inpatients obtained
      from clinical material in the second half of the year 2003 was determined. Using
      a microdilution assay, the minimum inhibitory concentration (MIC and MIC90,
      defined as the concentration that inhibits at least 90 percent of the tested
      strains) of 20 strains each of Staphylococcus aureus of the variety MSSA
      (susceptible to methicillin), Staphylococcus aureus of the variety MRSA
      (methicillin resistant), Staphylococcus haemolyticus, Streptococcus pyogenes,
      Enterococcus faecalis, Corynebacterium spec., Candida albicans and Candida
      parapsilosis was determined. All of the tested gram-positive bacteria turned out
      to be highly susceptible to tyrothricin with MICs <= 4mg/l. The tested yeast
      strains were susceptible to the polypeptide antibiotic as well, but (with MICs of
      16 mg/l and 32 mg/l, respectively) to a lesser extent. No acquired resistance of
      the tested strains was determined, indicating that the risk of resistance
      development against topically applied tyrothricin is only marginal, if there is
      any at all. Thus, long-term-, i.e. decade-long use of topically applied
      tyrothricin and its components in the local treatment of infected skin does not
      pose a major risk with respect to acquired resistance of originally susceptible
      gram-positive bacteria and yeasts, not even in the case of Staphylococcus aureus,
      both with MSSA and MRSA strains. The broad anti-bacterial and anti-fungal
      activity of tyrothricin combined with its lacking risk for resistance development
      make the antimicrobial peptide a valuable addition to our therapeutic
      armamentarium in the treatment of infected skin.

PMID- 25985582
TI  - Efficacy and safety of letosteine in the treatment of sputum thickening and
      expectoration difficulty in patients with respiratory diseases: a multicenter,
      randomized, double-masked, double dummy, positive drug parallel controlled trial.
AB  - This study aimed to compare the efficacy and safety of letosteine and ambroxol
      hydrochloride for the treatment of sputum thickening and expectoration difficulty
      due to either acute or chronic respiratory diseases. Patients (n = 240) were
      randomized to receive either letosteine + placebo (50 mg thrice daily, Group A)
      or ambroxol hydrochloride + placebo (30 mg thrice daily, Group B) orally for 5-14
      days. The primary outcomes comprised the total effectiveness rate and the total
      improvement rate. Secondary outcomes included: post-treatment IgA level changes
      and post-treatment therapeutic evaluation scoring of clinical symptoms. The full
      analysis set (FAS) comprised 113 patients in Group A and 116 in Group B. The
      total effectiveness rates were 95.58% for Group A and 95.69% for Group B. The
      total improvement rates were 99.12% and 99.14% for Group A and Group B,
      respectively. There were no significant differences between the two groups for
      any of the primary or secondary outcomes in either the FAS or the per protocol
      populations (PPS; all P-values > 0.05). Letosteine and ambroxol hydrochloride
      provided equivalent efficacy and safety in the treatment of sputum thickening and
      expectoration difficulty due to either acute or chronic respiratory diseases.

PMID- 25985583
TI  - Mycophenolate mofetil attenuates myocardial ischemia-reperfusion injury via
      regulation of the TLR4/NF-kappaB signaling pathway.
AB  - It has been well documented that the Toll-like receptor 4 (TLR4)/NF-kappaB
      signaling pathway mediates early inflammatory responses during myocardial
      ischemia and reperfusion (MI/R). Mycophenolate mofetil (MMF), an
      immunosuppressive agent, has been shown to confer protective effects against
      ischemia/reperfusion injury, possibly through its immunosuppressive and anti
      inflammatory actions. The aim of the present study was to investigate whether MMF
      could modulate the TLR4/NF-kappaB signaling, inhibit cell apoptosis and
      subsequently attenuate MI/R injury. MMF (20 mg/kg) or vehicle was administered to
      SD rats by gavage. The rats were then subjected to MI/R injury. The results
      showed that after MI/R, the expressions of myocardial TLR4 and NF-kappaB were
      significantly increased, and apoptosis of cardiomyocytes was induced, as
      evidenced by the decreased mitochondrial membrane potential (MMP), decreased Bcl
      2 protein level, and increased Bax expression. Administration of MMF attenuated
      MI/R injury. Further studies demonstrated that MMF inhibited the induction of
      TLR4, NF-kappaB and Bax expression, and restored the expression of bcl-2.
      Moreover, increased myeloperoxidase activity and serum level of tumor necrotic
      factor alpha induced by MI/R injury were also inhibited by MMF treatment. In
      conclusion, our results demonstrated that MMF attenuates MI/R injury through
      inhibition of the TLR4/NF-kappaB signaling pathway, which led to reduced
      inflammatory reaction and subsequently myocardial cell apoptosis.

PMID- 25985584
TI  - Gender differences in the gene expression profiles of glucose transporter GLUT
      class I and SGLT in mouse tissues.
AB  - Glucose transporters play key roles in controlling blood sugar levels and are
      recognized as the pharmacological targets of antidiabetic agents. In the present
      study, we compared the gene expression profiles of glucose transporter GLUT class
      I and SGLT isoforms in the skeletal muscle, heart, liver, kidney, and brain of
      male and female mice. The expression profiles of GLUT1 -4 and SGLT1 -2 in male
      mouse tissues were similar to those previously reported. Significant gender
      differences were observed in mRNA expression in terms of individual these glucose
      transport systems and the tissues examined. Especially, all of the corresponding
      mRNAs of renal GLUT class I and SGLT isoforms were expressed at higher levels in
      female mice than in male mice. However, no significant differences were observed
      in serum glucose concentrations between male and female mice. These results
      strongly suggest that prominent gender differences exist in the gene expression
      profiles of these glucose transporters in mouse tissues, and that the
      quantitative and functional multiplicities of glucose transporters may contribute
      to the successful regulation of blood glucose concentrations irrespective of
      gender differences.

PMID- 25985586
TI  - Can OSHA update the PELs?

PMID- 25985585
TI  - Polyphenols in Ammania auriculata: structures, antioxidative activity and
      cytotoxicity.
AB  - Chemical and biological investigations of the extract of Ammania auriculata
      (Lytheraceae) resulted in the identification of eight polyphenols (1 - 8) for the
      first time from this plant, including the gallotannin, 2,3,6-tri-O-galloyl
      (alpha,beta)-4C1-glucopyranose (8), for which 1D and 2D-NMR spectra were recorded
      and assigned for the first time. The structures of all isolates (1 - 8) were
      elucidated by conventional methods, spectroscopic analysis, including 1D and 2D
      NMR, and by HR-ESIMS as well. All of the isolated compounds were evaluated for
      their antioxidant activities, determined by the DPPH and ORAC methods and for
      their cytotoxicity against the keratinocyte cell line HaCaT using the neutral red
      assay (NRU) and cell cycle analysis. Compounds 1, 3, 4, 5, and 6 significantly
      inhibited reactive oxygen species production with ED50 values between 3.22 and
      9.79 MUg/ml. Compounds 1, 3, 4, and 5 showed cytotoxic activity against HaCaT
      cells with IC50 values between 30.7 and 84.1 MUg/ml. The new galloyl glucose (8)
      was found not cytotoxic. Ellagitannins, 2,3-hexahydroxy-((alpha/beta)
      glucopyranose (1) and 1 -0-galloyl 2,3-hexahydroxy-(alpha)-glucopyranose (5)
      possess remarkable antioxidative and comparably weak cytotoxic activity.

PMID- 25985588
TI  - Create workplace structure with visual signals and signs.

PMID- 25985587
TI  - Agricultural safety, sometimes forgotten.

PMID- 25985589
TI  - Ensuring full protection.

PMID- 25985590
TI  - Arc flash & flash fire apparel: multi-hazard protection.

PMID- 25985591
TI  - FYI: PPE acronyms you should know.

PMID- 25985592
TI  - Put safety eyewear to the test: ask for proof.

PMID- 25985593
TI  - Clear and calm measures.

PMID- 25985594
TI  - Three steps to safely collect combustible dust in any environment.

PMID- 25985595
TI  - Research finds big benefits in blended learning.

PMID- 25985596
TI  - Can your electrical infrastructure weather a natural disaster?

PMID- 25985597
TI  - Elements of a quality maintenance program.

PMID- 25985599
TI  - Toward compliance or global class?

PMID- 25985598
TI  - Incentives and rewards: lazy or excellent management?

PMID- 25985600
TI  - Mutual goals in preventive care.

PMID- 25985601
TI  - Fourscore in South Dakota: lowering risk for longer life.
AB  - Life expectancy at birth in South Dakota is 79.5 years, ranking 18th longest in
      the U.S. South Dakota county-level life expectancies range from 73.2-82.1 years.
      County-level life expectancies correlate significantly with tobacco smoking,
      physical inactivity, obesity, diabetes, poverty and infant mortality rates, where
      counties with higher rates of smoking, inactivity, obesity, diabetes, poverty and
      infant mortality have shorter life expectancies. The critical disparity in life
      expectancy is the 12-year gap between American Indian and white South Dakotans.

PMID- 25985602
TI  - Lifestyle: importance of a balanced diet and physical activity.
AB  - The goal of this article is to provide evidenced-based information to help the
      clinician understand the relationship of lifestyle (nutritional and activity)
      approaches to disease prevention and health promotion. Major health factors
      correlated to these activities of daily life will be reviewed.

PMID- 25985603
TI  - Prevention of childhood obesity: a review of the current guidelines and
      supporting evidence.
AB  - BACKGROUND: Childhood obesity is considered by many one of the biggest public
      health issues facing our country. In the U.S. almost one in three children are
      overweight and one in five are obese. This article aims to outline the current
      childhood obesity prevention measures as well as discuss programs that have had
      success in reducing childhood overweight and obesity. METHODS: Recent literature
      on prevention of childhood obesity was reviewed. There was a focus on systematic
      reviews, random controlled trials and well-designed observational studies.
      RESULTS: Evidenced-based prevention of childhood obesity demonstrates that there
      is a benefit to programs that focus on a collaboration of community/school,
      primary health care, and home/family based interventions that involve both a
      physical activity and dietary component. Successful programs have more efficacy
      if they are longer in duration and initiated for children in middle school or
      younger. DISCUSSION: The most recent recommendations regarding prevention of
      childhood obesity focus on increased exercise and improved diet to prevent
      childhood obesity. Despite these clear recommendations and general consensus for
      them, childhood obesity continues to increase. The evidence supports a
      collaborative effort with multiple stakeholders to reverse the trend in childhood
      obesity.

PMID- 25985604
TI  - The metabolic syndrome.
AB  - The metabolic syndrome is a constellation of signs and symptoms which increase a
      patient's risk of developing heart disease and diabetes mellitus. The metabolic
      syndrome or syndrome X includes central obesity, hypertension, hyperglycemia, and
      dyslipidemia. Diagnosing the metabolic syndrome in a patient identifies areas
      that can be addressed and with appropriate treatment can lower the risk of
      diabetes and cardiovascular disease. One area of controversy is the question:
      does the metabolic syndrome as a whole increase risk more than the sum of its
      parts? Recognizing the metabolic syndrome early with treatment can improve our
      patients' long-term health.

PMID- 25985605
TI  - Implementing the 2013 cholesterol management guidelines into clinical practice.
AB  - Although a reduction in atherosclerotic cardiovascular disease (ASCVD) events
      remains the ultimate goal in cholesterol management, there has been a change in
      recommended cholesterol management in patients with increased risk. The objective
      in cholesterol management is no longer reducing low-density lipoprotein (LDL) to
      a particular target value, but ensuring that patients with the highest ASCVD risk
      are treated with the most potent statin therapy. The previous practice of statin
      therapy cessation and routine monitoring for adverse events has also been
      scrutinized by the recent American Heart Association (AHA)/American College of
      Cardiology (ACC) guidelines. Identifying patients who are at risk now requires
      the utilization of a novel tool called the ASCVD pooled cohort calculator. The
      following article will guide the clinician on implementing the current AHA/ACC
      guidelines into clinical practice.

PMID- 25985606
TI  - Implementing effective hypertensive management--review of the 2014 high blood
      pressure management guidelines.
AB  - The Joint National Committee (JNC 8) hypertension guidelines have modified the
      blood pressure goals across the spectrum of disease processes and patient
      characteristics. This article will elucidate these changes and help clinicians
      improve the clinical care of patients with hypertension. Patients are now
      conceptually categorized into two different patient populations: those who are at
      a low- or high-risk of developing atherosclerotic cardiovascular disease (ASCVD)
      or chronic kidney disease (CKD). A low-risk population comprises patients aged 60
      or older who do not have disease processes that enhance ASCVD or CKD disease
      development. High-risk patients are those with CKD and/or diabetes, and patients
      less than 60 years of age who remain at risk of future development. The current
      recommendation for blood-pressure goals in the low- and high-risk population is
      150/90 mmHg and 140/90 mmHg, respectively. In all patients considered for
      antihypertensive therapy, the first line antihypertensive pharmacotherapy should
      include either a thiazide-type diuretic, calcium channel blocker (CCB),
      angiotensin-converting enzyme inhibitor (ACEI), or an angiotensin receptor
      blocker (ARB). Beta blockers no longer have a role as standalone therapy.
      Thiazide- type diuretics and CCB continue to demonstrate benefit in the African
      American population and should continue to be considered as first line agents.
      CKD patients with concomitant hypertension should be treated with an ACE
      inhibitor or ARB.

PMID- 25985607
TI  - Preconception and prenatal care--useful tools for providers of women's health.
AB  - Health care providers have a unique opportunity to change the behaviors of their
      patients. Preconception and prenatal care allow for interventions to abate risky
      behaviors that can affect not only the woman but also her developing fetus. If we
      can assist the reproductive age woman in modifying her high-risk activities,
      there will be improved birth outcomes and healthier mothers to care for their
      offspring. Alcohol and tobacco use, sexually transmitted infections and obesity
      are the top four modifiable risk factors. This article will address the impact
      that these behaviors have on women and tools to assist the health care provider
      in changing these bad habits and promoting healthy pregnancies. The theory of
      "fetal origins of disease" is emerging as one of the most powerful and compelling
      reasons to engage our patients before and during their pregnancy. Preventive
      medicine needs to start in the womb if we want to have the highest impact on
      healthy adulthood.

PMID- 25985608
TI  - Antibiotic stewardship: a focus on ambulatory care.
AB  - Antibiotic resistance is one of the major health threats facing modern medicine.
      While there are many tactics to address this issue, antibiotic stewardship has
      been shown effective in reducing antimicrobial resistance, adverse drug effects,
      mortality and health care cost. Most antibiotic stewardship programs have evolved
      within acute care settings where the bulk of resistant infections are identified.
      Unfortunately, hospitals are just the tip of the iceberg in terms of overall
      antibiotic use. The vast majority of the antibiotic prescriptions are dispensed
      in ambulatory care settings, making this a critical target for stewardship
      programs. This article discusses the global need for antibiotic stewardship,
      highlights the importance of outpatient stewardship, and discusses strategies and
      challenges for implementation of stewardship in community settings.

PMID- 25985609
TI  - Emerging infections and old friends: remaining prepared in South Dakota.
AB  - Recent reports of serious infection outbreaks internationally remind us of the
      importance of accurate information and continual vigilance. The Ebola outbreak in
      West Africa has captured headlines as the most severe outbreak in the history of
      this disease. West Nile disease, measles, pertussis and tuberculosis infect South
      Dakota patients on a yearly basis. A significant rise in syphilis cases has
      prompted recommendations for increased prenatal screening. The more unusual viral
      diseases, Ebola, Middle East respiratory syndrome (MERS) and Chikungunha virus,
      receive media attention but present minimal risk to the state, while the annual
      influenza epidemic continues to plague us all. We review these infections, both
      old and emerging, and describe national and local preparedness practices.

PMID- 25985610
TI  - STD prevention: why limit ourselves to just an ounce?
AB  - When Ben Franklin said, "An ounce of prevention is worth a pound of cure" he was
      not likely referring to sexually transmitted diseases (STDs). Preventing an STD
      is greatly preferred to treating not just that STD but the ever-expanding circle
      of STDs which may arise from the index case. STD risk is closely linked to sexual
      behaviors, making effective prevention quite challenging. But there are more
      arrows in our prevention quiver than simply telling people to use condoms.
      Because many STDs are asymptomatic, there is a clear role for screening at-risk
      populations. Identifying those at-risk populations can only happen when we obtain
      meaningful sexual histories. Individuals diagnosed with STDs must be treated
      appropriately, but also treating their partners will limit further transmission.
      Expedited partner therapy is one approach to treating STD contacts. Vaccination
      against human papillomavirus (HPV) is an under-utilized method of STD prevention.
      Pre-exposure prophylaxis (PrEP) is a recent development for HIV prevention in
      some high-risk individuals. Another recent strategy is HIV treatment as
      prevention, in which we reduce the pool of potential HIV transmitters. Each of
      these prevention tools is simply another building block to place upon the
      foundation of the ABCs: Abstinence, Being faithful, and Condom use.

PMID- 25985611
TI  - Medicinal and recreational marijuana: what are the risks?
AB  - With the recent legalization of recreational marijuana in Colorado, Washington,
      Alaska, the District of Columbia and legislation pending for both medical and
      recreational marijuana in several other states, it is important for the facts
      regarding its potential for serious mental health consequences to be known.
      Little has been said about the psychiatric risks of this substance, particularly
      in youth. Several studies have shown increased rates of depression, anxiety and
      schizophrenia among those who use marijuana on a regular basis. In addition,
      permanent loss of IQ and structural changes in the brain have been demonstrated
      with habitual use. Legalization of marijuana for recreational use can influence
      an adolescent's perception of this substance as "safe." In states that have
      legalized marijuana for medical purposes, there is the very real problem of
      "diversion." As many as 34 percent of 12th-graders who use marijuana in states
      with legalized marijuana had obtained it from a person who had received it
      through a prescription.

PMID- 25985612
TI  - Tobacco quitline outcomes for priority populations.
AB  - BACKGROUND: Despite declining rates of tobacco use, certain subgroups still
      experience a disproportionate risk for tobacco-related health issues. The South
      Dakota QuitLine identifies five priority population subgroups as the following:
      American Indians, tobacco users receiving Medicaid, youth, pregnant women, and
      spit tobacco users. The purpose of this study was to describe South Dakota
      QuitLine use among priority population subgroups and to measure associated
      cessation rates and service satisfaction. METHODS: Priority population subgroups
      comprised 22.6 percent (9,558 out of 42,237) of South Dakota QuitLine
      participants during a six-year period (2008-2013). Of the 34,866 total
      participants eligible for seven-months follow-up, 15,983 completed a telephone
      survey that measured tobacco quit status and service satisfaction (45.8 percent
      overall response). Eligible priority population subgroups had a 41.9 percent
      response (3,094 out of 7,388). RESULTS: The seven-month tobacco quit rate for the
      non-priority population group (46.9 percent) was higher than the quit rate for
      pregnant women (42.3 percent), youth (37.5 percent), American Indians (38.1
      percent), Medicaid participants (35.7 percent) and participants with more than
      one priority subgroup designation (35.1 percent). The quit rate for spit tobacco
      users was highest overall (57.3 percent). All subgroups were satisfied with South
      Dakota Quitline services (>= 3.5/4.0 scale; 4 = very satisfied). CONCLUSIONS:
      Tobacco users in high risk and underserved population subgroups of the South
      Dakota QuitLine seek cessation services. Quit rates were overall favorable and
      varied between population subgroups (35.1-57.3 percent). Health care providers
      play a vital role in early identification of tobacco use and referral to
      cessation services for priority populations. Providers should assess tobacco use,
      advise users to quit, and refer to the South Dakota QuitLine.

PMID- 25985613
TI  - Breast cancer screening.
AB  - Decreasing breast cancer mortality represents a high priority for patients and
      their health care providers. Assessment of individual risk combined with
      discussion of risks and benefits of screening is essential in assisting patients
      in making their screening decisions. This article reviews the literature in order
      to provide primary care providers information regarding risk assessment,
      controversies regarding screening including age to start screening, best interval
      for screening, age to stop screening and methods to perform screening. Providers
      are encouraged to initiate this conversation with their patients.

PMID- 25985614
TI  - Skin cancer prevention and screening.
AB  - Skin cancer is the most common and recognizable of all cancers. The human dermis
      can turn malignant due to excessive solar exposure and chronic injury, with the
      influence of genetic risk and inherited pigmentation. Basal cell carcinoma, the
      most common skin cancer in lighter pigmented individuals, spreads locally, and
      usually appears pearly and often ulcerative. Squamous cell carcinoma, the most
      common skin cancer in darker pigmented people, metastasizes to lymph nodes 2-5
      percent of the time, appears often scaly, smooth, nodular, ulcerative, or even
      pigmented. Malignant melanoma accounts for 2 percent of skin cancers, but for the
      vast majority of skin cancer deaths. All three can mimic each other. Solar or
      ultraviolet (UV) light exposure is the most common carcinogen; however, any
      chronic irritant can increase the risk, and efforts to avoid such exposure is
      apropos. Though not yet absolutely proven, skin cancer research strongly supports
      the following statements: sunscreen is protective, tanning devices are causative,
      and the routine screening of high-risk individuals is preventative. Authorities
      strongly recommend avoiding excess sun and UV light, using sunscreen, and keeping
      a watchful eye for unusual skin lesions.

PMID- 25985615
TI  - Stop cancer colon. Colorectal cancer screening--updated guidelines.
AB  - Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers in the
      U.S. Its incidence and mortality have shown a decreasing trend over the last
      several decades. The greatest contribution to this trend has been colorectal
      cancer screening. Colonoscopy continues to be the preferred screening modality.
      However, recommendations for the use of screening tests other than colonoscopy
      have generated much interest. Guidelines regarding current screening and
      surveillance recommendations have recently been updated by expert panels, such as
      the U.S. Multi-Society Task Force, National Comprehensive Cancer Network and
      National Institute of Health. A review of the updated guidelines as well as a
      PubMed search for articles dating 2006 to present relating to colorectal cancer
      screening and surveillance was performed. We discuss the importance of colorectal
      screening and highlight updates to current colorectal cancer screening and
      surveillance guidelines.

PMID- 25985616
TI  - Why prostate cancer screening is necessary.

PMID- 25985617
TI  - DAKOTACARE update: DAKOTACARE's health and well-being: a leader in workplace
      wellness.

PMID- 25985618
TI  - Quality focus: colorectal cancer prevention and detection.

PMID- 25985619
TI  - Patient education. Enjoying balance.

PMID- 25985620
TI  - [Cancer stem cells and systems biology].

PMID- 25985621
TI  - [The fundamental concept of cancer stem cell and the progress in cancer stem cell
      research].
AB  - Stem cell is defined as the cell having the ability of self-renew and
      differentiation. Due to the development of flow cytometric analysis and
      immunodeficient mouse model, stem cell research had dramatically progressed.
      Based on the knowledge of normal stem cell, concept of cancer stem cell, which
      have self-renewal ability and tumorigenic potential in immunodeficient mouse,
      have been established. Cancer stem cell population in various cancers has been
      identified using cell surface markers, such as CD44, and therapeutic strategies
      have been developing. Moreover, as accumulating the knowledge of cancer stem
      cell, it has revealed that cancer stem cell has high plasticity. We introduce
      here the evolving cancer stem cell concept.

PMID- 25985622
TI  - [Cancer stem cell research toward therapeutics].
AB  - The capacity of cancer stem cells, or cancer-initiating cells, to both provide
      mature tumor cells and perpetuate themselves through self-renewal is crucial to
      initiate and maintain tumorigenesis, and has become the focus of intense research
      interest as a promising source of new therapeutic strategies. However, many
      scientific challenges and technical barriers remain to be solved before recent
      findings can be translated into effective therapeutics. Here we highlight the
      latest advances in our knowledge of cancer stem cells, and provide a critical
      perspective on the clinical benefits promised by this developing area of
      research.

PMID- 25985623
TI  - [The cancer stem cell model in hematological malignancies].
AB  - Technological advances such as the high-throughput sequencing are providing us
      novel aspects and perspectives of cancer stem cells (CSCs). Current evidences
      support a model where multiple subclones persist, rather than a simple
      hierarchical model with CSCs. The presence of multiple subclones contributes to
      increase in fitness and robustness of a cancer, which is reminiscent of the
      stability in ecosystems. The latest report describing the sequencing of
      peripheral-blood cells from unselected persons revealed that clonal hematopoiesis
      with somatic mutations already exists in a fair percentage of elderly persons.
      The analysis also shed light on some epigenetic modifiers as the driver genes of
      clonal hematopoiesis. In this article, we review the recent evolution of CSC
      model in hematology.

PMID- 25985624
TI  - [Cancer stem cells and the niches].
AB  - The fate of stem cells is tightly controlled by specialized microenvironments
      (niches). Cell cycle quiescence is a key behavior of stem cells, which protects
      them from being exhausted by exogenous insults. Since the discovery of cancer
      stem cells, which are quiescent and thus resistant to anti-cancer therapy, there
      has been considerable interest regarding whether or not there are distinct niches
      for quiescent and expanding cancer cells, respectively. In our recent study using
      whole-mount immunofluorescence imaging techniques, we found that arteriolar
      niches promote hematopoietic stem cell (HSC) dormancy and that the NG2+ peri
      arteriolar niche cells themselves are quiescent, suggesting that bone marrow
      arterioles comprise a specialized microenvironment that promotes quiescence of
      both HSCs and niche cells. In this review, we will argue about the advance of our
      knowledge on normal stem cell niches and the roles of microenvironments in
      cancer.

PMID- 25985625
TI  - [Metabolism enzyme controls cancer stemness].
AB  - Cancer stem cells are known to influence survival, chemoresistance, relapse and
      metastasis. Pyruvate kinase M2 (PKM2) maintains aerobic glycolysis in cancer
      cells and stimulates cell proliferation by controlling Warburg effect. In
      addition, PKM2 translocates to nucleus and up-regulates PDK1 expression by
      controlling its transcription. PKM2 confers malignant potential by controlling
      both metabolism and transcriptional regulation. Tumor invasion is initiated with
      the change of epithelial-mesenchymal transition (EMT) in cancer cell. After EMT
      induction, in parallel with E-cadherin down-regulation and vimentin up
      regulation, the expression of PKM2 was increased both in transcriptional and
      translational level and PKM2 translocated into nucleus. TGIF2 was identified
      which interacted with PKM2 in nucleus in response to EMT induction, which was
      considered to have a key role in controlling EMT induction. We performed
      immunohistochemical staining with specific antibody to PKM2 using clinical
      samples of colorectal cancers. Clinicopathological analysis showed that PKM2
      positivity significantly correlated with lymph node metastasis and distant organ
      metastasis. In conclusion, our data suggested that PKM2 nuclear function had a
      crucial role in controlling invasion and metastasis.

PMID- 25985626
TI  - [Application of reprogramming technology for cancer research].
AB  - Cancer is generally developed through accumulation of multiple genetic mutations.
      Epigenetic abnormalities of DNA methylation and histone modification patterns
      were also found in most cancer cells. Although induced pluripotent stem cells
      (iPSCs) can be generated through epigenetic reorganization without affecting the
      underlying genomic sequencing, they have some shared characteristics with cancer
      cells, which include unlimited growth potential. Taking advantages of such
      properties of iPSC derivation, the reprogramming technology is applicable not
      only for regenerative medicine but also for cancer research. Here, we introduce
      the potential application of iPSC technology for better understandings of cancer
      biology. Especially, we would like to propose the role of cellular identity in
      cancer development.

PMID- 25985627
TI  - [Xenotransplantation assay for cancer stem cells].
AB  - Immunodeficient mice are widely used to reconstitute human hematopoiesis by
      xenotransplantation of hematopoietic stem cells(HSCs). This humanized mouse model
      provides a powerful tool to evaluate biological properties of human HSCs in vivo.
      This systems have been used also to study human cancer stem cells. Currently, NOD
      -background immunodeficient strains are the most efficient to reconstitute human
      hematopoiesis in the mice, but even they are not enough for cancer stem cell
      assay. NOD strain has multiple immune deficiencies. For this reason, to improve
      and establish a new xenotransplantation model, lymphoid-depleted strains have
      been backcrossed into the NOD-inbred strain to introduce such numerous NOD
      specific abnormalities. Our positional genetic study has located the NOD-specific
      polymorphic Sirpa as a molecular responsible for its high xenograft efficiency.
      We established B6-based immunodeficient strains harboring NOD-Sirpa (BRGS) which
      showed efficient human cell engraftment comparable to that of NOD -background
      strains. Consequently, BRGS mice are free from NOD-related abnormalities. This
      simplified strain should be useful in future xenotransplant study of cancer stem
      cells.

PMID- 25985628
TI  - [Methionine metabolism regulates maintenance and differentiation of human ES/iPS
      cells].
AB  - Embryonic stem (ES) and induced pluripotent stem (iPS) cells are pluripotent and
      can give rise to all cell types. ES/iPS cells have a unique transcriptional
      circuit that sustains the pluripotent state. These cells also possess a
      characteristically high rate of proliferation as well as an abbreviated G1 phase.
      These unique molecular properties distinguish ES and iPS cells from somatic
      cells. Mouse ES/iPS cells are in a high-flux metabolic state, with a high
      dependence on threonine catabolism. However, little is known about amino acid
      metabolism in human ES/iPS cells. Recently, we reported that human ES/iPS cells
      require high amounts of methionine (Met) and express high levels of Met
      metabolism enzymes (Shriaki N, et al: Cell Metabolism, 2014). Met deprivation
      results in a rapid decrease in intracellular S-adenosyl-methionine (SAM),
      triggering the activation of p53 signaling, reducing pluripotent marker gene
      NANOG expression, and poising human ES/iPS cells for differentiation, follow by
      potentiated differentiation into all three germ layers. However, when exposed to
      prolonged Met deprivation, the cells went to apoptosis. In this review, we
      explain the importance of SAM in Met metabolism and its relationship with
      pluripotency, cell survival, and differentiation of human ES/iPS cells.

PMID- 25985630
TI  - [Cell cycle regulation in cancer stem cells].
AB  - In addition to the properties of self-renewal and multipotency, cancer stem cells
      share the characteristics of their distinct cell cycle status with somatic stem
      cells. Cancer stem cells (CSCs) are maintained in a quiescent state with this
      characteristic conferring resistance to anticancer therapies that target dividing
      cells. Elucidation of the mechanisms of CSC quiescence might therefore be
      expected to provide further insight into CSC behaviors and lead to the
      elimination of cancer. This review summarizes several key regulators of the cell
      cycle in CSCs as well as attempts to define future challenges in this field,
      especially from the point of view of the application of our current
      understandings to the clinical medicine.

PMID- 25985629
TI  - [Regulation of cancer behavior mediated by mTOR signal].
AB  - Proliferation of cancer cells requires activation of signals that response to
      nutrients. One of the major coordinators of nutrient signals is
      mammalian/mechanistic target of rapamycin (mTOR). mTOR complex 1 (mTORC1)
      controls multiple cellular processes, including protein synthesis, glucose
      metabolism, fatty acid and sterol synthesis, mitochondrial biogenesis, and
      autophagy. Although inhibitors of mTORC1 have been developed, effectiveness of
      the inhibitors for cancer eradication appears to be limited, because of presence
      of several feed-back signals. In addition, leukemia stem cells might survive
      against mTOR inactivation through common mechanisms by which normal hematopoietic
      stem cells are maintained in the niche. Advances in understanding of how mTOR
      signaling is involved in mechanisms of stem cells may lead to novel therapeutic
      approaches that can successfully eradicate cancer.

PMID- 25985631
TI  - [TGF-beta signaling in cancer stem cells].
AB  - Cancer stem cells are the cellular sources of the vast majority of mature cancer
      cells and are reportedly responsible for the recurrence of disease following anti
      cancer therapy. Recent advantages in the cancer stem cell research field have
      indicated that TGF-beta signaling pathway plays an essential role for the
      maintenance of cancer stem cells via regulating cancer stemness, quiescence,
      epithelial -mesenchymal transition (EMT), or therapeutic resistance in vivo.
      Therefore, the outcome of these investigations will hopefully be the development
      of novel agents that can specifically control both augmentation and suppression
      of TGF-beta signaling pathway in cancer stem cells, and thereby provide a novel
      avenue for curative cancer patient therapy.

PMID- 25985632
TI  - [Redox regulation in cancer stem cells].
AB  - CD44 was identified as a cell surface marker for cancer stem cells (CSCs) in
      various epithelial tumor. However, function-based evidence to support the role of
      CD44 in CSCs was not known. We found that expression of CD44, in particular
      variant forms of CD44 (CD44v), suppresses reactive oxygen species (ROS) levels by
      promoting the synthesis of reduced glutathione(GSH), a primary intracellular
      antioxidant. CD44v stabilizes xCT, a subunit of a glutamate-cystine transporter,
      and thereby promotes the uptake of cystine for GSH synthesis. Our findings reveal
      a novel function for CD44v in protection of CSCs from high levels of ROS in the
      tumor microenvironment.

PMID- 25985633
TI  - [Immune regulation of cancer stem cells].
AB  - Emerging evidences have revealed the role of tumor-associated immune cells and
      their derivatives in the regulation of tumor progression. In particular, recent
      studies have clarified that various tumor-associated immune regulatory systems,
      which include tumor-infiltrating myeloid cells and pro-inflammatory cytokines,
      for regulating the maintenance and activation of cancer stem cells. The networks
      formed by immune cells and cancer stem cells play a critical role in further
      amplifying infiltration of pro-tumor immune cells and inflammatory cascades, and
      promoting cancer stemness. Further clarification about the immune-mediated
      regulation of cancer stem cell activities should provide therapeutic implication
      against cancer stem cells and treatment-resistant variants of cancer cells.

PMID- 25985634
TI  - [Regulation of leukemic stem cells by manipulating the Geminin activity].
AB  - Geminin regulates cellular proliferation and differentiation through the
      inhibition of DNA replication licensing and chromatin remodeling, respectively,
      to sustain the activity of hematopoietic stem cells (HSCs) and possibly that of
      leukemic stem cells (LSCs). Thus, Geminin is presumed to act as a cell fate
      determinant by turning on and off self-renewal and differentiation of the stem
      cells. We visualized Geminin expression by generating knock-in mice expressing
      Geminin fusion protein with enhanced yellow fluorescent protein. We further
      established a new method for manipulating the Geminin expression level and
      activity by generating cell -penetrating (CP) - Geminin. Here we argue for a new
      strategy for expanding HSCs ex vivo to provide a cellular source of HSCs for
      transplantation and further for eradicating LSCs, which are resistant to
      conventional chemotherapy.

PMID- 25985635
TI  - [Cancer stemness and circulating tumor cells].
AB  - The principle concept of cancer stem cells (CSCs) giving rise to the
      carcinogenesis, relapse or metastasis of malignancy is broadly recognized. On the
      other hand, circulating tumor cells (CTCs) also plays important roles in relapse
      or metastasis of malignancy, and there has been much focused on the association
      between CSCs and CTCs in cancer cases. The technical innovations for detection of
      CTCs enabled us to unveil the nature of CTCs. We now realize that CTCs isolated
      by cell surface antibodies, such as DCLK1, LGR5 indicated CSC properties, and
      CTCs with epitherial-mesenchymal transition(EMT) phenotype showed characteristics
      of CSCs.

PMID- 25985636
TI  - [Molecular targeted therapy for leukemic stem cells].
AB  - Acute myelogenous leukemia (AML) originates from self-renewing leukemic stem
      cells (LSCs), an ultimate therapeutic target for AML. LSCs play a central role in
      the propagation of leukemia through their unique stem cell like properties, and
      LSCs share the many functional molecules with their normal counterpart
      hematopoietic stem cells (HSCs). For the establishment of LSCs-specific
      therapeutic approaches, it is quite important to understand the biological
      differences between LSCs and HSCs. Recent, studies have succeeded in clarifying
      these biological differences. In this review, I would like to introduce the
      biological significance of LSCs and discuss the molecular targeted therapy
      against LSCs.

PMID- 25985637
TI  - [Identification and targeting of multiple myeloma stem cells].
AB  - Multiple myeloma(MM) is characterized by the clonal expansion of malignant plasma
      cells. In xenograft models, CD19-CD38++ MM plasma cells engrafted and rapidly
      propagated MM, indicating that MM plasma cells, which are terminally
      differentiated cells, include MM-initiating cells. Bone marrow niche for MM
      initiating cells are now being investigated extensively. MM patients harbor
      phenotypic CD19+ B cells expressing the immunoglobulin gene sequence and the
      idiotype unique to the individual myeloma clone. CD19+ clonotypic B cells include
      "pre-myeloma stem cells", and additional oncogenic hits are likely to be needed
      before developing myeloma disease from them. Prospective identification of CD19+
      "pre-myeloma stem cells" is important for diagnosing pre-myeloma status and for
      developing the methods for the prevention of multiple myeloma.

PMID- 25985638
TI  - [Clinical research of targeting therapy for cancer stem cells].
AB  - To achieve cure is difficult and progression after response to treatment is
      common for patients with several type of malignancies. One possible reason is
      existence of cancer stem cells, which have self-renewal activity and resistance
      to chemotherapy and radiotherapy. Several cellular markers and signal pathways
      are investigated to identify cancer stem cell. Targeting cancer stem cell is
      considered as promising to achieve cure in combination with other treatment.
      Although no cancer stem cell specific treatment is established at the present
      moment, several targeting agents are under development. We conducted a phase I
      study of specific inhibitor of xCT, a glutamate-cystine transporter, of CD44
      splice variant (CD44v) expressed cancer stem like cell to confirm the mode of
      action. Clinical study of combination therapy with cisplatin is ongoing.

PMID- 25985639
TI  - [Breast cancer stem cell research utilizing clinical specimens].
AB  - The existence of cancer stem cells in solid tumors was first reported in 2003
      based on the analyses of human breast cancers. Analyses of clinical specimens are
      especially important for the advancement of human cancer stem cell research. For
      example, the analyses of breast cancer stem cells directly isolated from human
      breast cancer specimens identified the microRNAs that are involved in the
      regulation of human breast cancer stem cells. In addition, human breast cancer
      xenograft is an attractive model to analyze cancer stem cells, as well as cancer
      metastases that have profound effect on the long-term survival of breast cancer
      patients. We will present the current status of human breast cancer stem cell
      research that utilizes clinical specimens.

PMID- 25985640
TI  - [Brain tumor stem cells].
AB  - Glioblastoma multiforme (GBM) is the most frequent and aggressive brain tumor,
      and which harbors not only rapidly dividing cells but also small populations of
      slowly dividing and dormant cells with tumorigenesity-, self-renewal-, and multi
      lineage differentiation capabilities. GBM stem cells (GSCs), which are resistant
      to conventional chemo -radiotherapy and may be a cause of local recurrence and
      dissemination. Additionally, heterogeneity of GSCs in the same tumor had been
      shown by the innovation of microarray and sequencing technology. However, outcome
      in patients with GBM remains unsatisfactory. Accumulation of the clinical
      evidence and basic research findings targeting for GSCs and their specific
      microenvironments (GSC niches) raise the possibility of new treatments to
      overcome GBM.

PMID- 25985641
TI  - [Pancreatic cancer stem cell].
AB  - Prognosis of pancreatic cancer remains dismal due to the resistance against
      conventional therapies. Metastasis and massive invasion toward surrounding organs
      hamper radical resection. Small part of entire cancer cells reveal resistance
      against chemotherapy or radiotherapy, increased tumorigenicity and migratory
      phenotype. These cells are called as cancer stem cells, as a counter part of
      normal stem cells. In pancreatic cancer, several cancer stem cell markers have
      been identified, which enabled detailed characterization of pancreatic cancer
      stem cells. Recent researches clarified that conventional chemotherapy itself
      could increase cancer cells with stem cell-phenotype, suggesting the necessity of
      cancer stem cell-targeting therapy. Based on these observations, pancreatic
      cancer stem cell-targeting therapies have been tested, which effectively
      eliminated cancer stem cell fraction and attenuated cancer progression in
      experimental models. Clinical efficacy of these therapies need to be evaluated,
      and cancer stem cell-targeting therapy will contribute to improve the prognosis
      of pancreatic cancer.

PMID- 25985642
TI  - [A tumor stem cell-specific marker identified by lineage tracing in the
      intestine].
AB  - Tumor therapies targeting tumor stem cells(TSCs) have been limited. One of the
      reasons is that TSC markers are often shared by normal stem cells (NSCs), and
      therapies targeting those marker-positive cells may cause severe injury to normal
      tissues. To solve the problem, we focused on doublecortin -like kinase 1 (Dclk1).
      In the normal intestines of Dclk1(creERT2/+); Rosa26(LacZ/+) mice, LacZ-labeled
      epithelial cells were scattered along villi after tamoxifen injection. In
      contrast, in Dclk1(creERT2/+); Rosa26(LacZ/+); Apc(Min/+) mice, intestinal tumors
      were occupied by LacZ-labeled tumor cells, and selective ablation of Dclk1
      positive cells using iDTR system resulted in regression of intestinal tumors
      without apparent damage to the normal intestines. Thus, Dclk1 appeared to be a
      marker that discriminates TSCs from NSCs in the intestine.

PMID- 25985643
TI  - [Remodeling of cancer stem cells in gastrointestinal cancer].
AB  - Gastrointestinal cancer such as gastric cancer and colon caner, occupies the
      majority of the cause of death due to the malignant tumor. Although some progress
      about the conquest of cancer is accepted through early diagnosis and the
      development of the endoscope treatment, the treatment, which directly targets the
      molecular mechanism of the carcinogenesis, is still poor. It therefore is
      necessary to analyze a process of carcinogenesis in detail. While the gene
      abnormality as the cause of cancer has been gradually clarified, the
      characteristic of the cancer stem cell has recently attracted as novel target for
      cancer therapy. In this report, I summarize about the present situation of a
      clarified cancer stem cell study and introduce a new trial to understand
      carcinogenesis mechanism by rebuilding the process of carcinogenesis until the
      acquisition of the cancer stem cell mainly on stomach and colon.

PMID- 25985644
TI  - [A roadmap toward total elimination of cancer].
AB  - Cancer stem cells (CSCs) were first experimentally identified in leukemia in
      1997, and following researches demonstrated the existence of CSCs in a variety of
      solid cancers. It has been reported that CSCs are responsible for tumorigenicity,
      chemoresistance, and metastasis as well as heterogeneity of cancers. Therefore,
      elimination of CSCs may be crucial to eradicate cancer. Recent reports indicate
      that CSCs from some solid cancers show phenotypic plasticity, and intrinsic or
      extrinsic signals can revert differentiated cancer cells back into CSCs. These
      traits of CSCs may cause problems in devising targeted therapy against CSCs in
      future. Here we discuss how we can achieve total elimination of cancer cells in
      light of recent progress in understanding of CSCs.

PMID- 25985645
TI  - [Design and analysis of clinical trials].
AB  - The purpose of a therapeutic clinical trial is to determine the value of a
      treatment. The main objectives of phase I trials have been to determine a dose
      that is appropriate for use in phase II and III trials and to determine
      information about the pharmacokinetics of distribution of the drug. Phase II
      trials have been performed to determine whether a particular regimen or drug is
      worthy of phase III evaluation. Phase III trials attempt to prove the usefulness
      of treatment and determine the new treatment strategy.

PMID- 25985646
TI  - [Chronic intestinal pseudo-obstruction].
AB  - Chronic intestinal pseudo-obstruction(CIPO) is a rare severe digestive disease in
      which clinical symptoms of intestinal obstruction appear without any mechanical
      cause. Pathophysiologically, CIPO shows ineffective intestinal propulsion due to
      an impairment of intestinal smooth muscle, enteric nervous system, and
      interstitial cells of Cajal(ICC). Sustained increased intra-bowel pressure often
      causes small intestinal malabsorption and bacterial translocation, and leads to
      malnutrition and blood stream infection (sepsis). Key points of the medical
      approach for CIPO are to improve nutritional status and reduce abdominal
      symptoms. Dietary cure and defecation control are the main options in mild cases,
      whereas home-parenteral-nutrition(HPN) and decompression therapy are often needed
      in severe cases. Stimulant laxatives, prokinetics and herbal medicine are usually
      used but often in fail. Percutaneous endoscopic gastrojejunostomy(PEG-J) tube may
      be burdenless compared to conventional ileus tube. Most important points in the
      management of this disease are to make a correct diagnosis as early as possible
      and avoid unnecessary surgery. However, no clear diagnostic criteria have been
      established so far. Manometry, scintigraphy, and full-thickness biopsy are the
      major examination for the CIPO diagnosis in the Western countries; however these
      specialized examinations are not popular in Japan. Therefore the Research
      Group(chief investigator, Atsushi Nakajima) proposed Japanese diagnostic criteria
      in 2009 to facilitate the diagnosis of this rare disease by the general
      physician. In 2013, we have reported that cine-MRI is a non-invasive diagnostic
      method for CIPO. Although further data are eagerly awaited, it can become a
      promising diagnostic tool in CIPO patients. Furthermore the Japanese criteria
      have been revised, and in 2014, the comprehensive criteria from a child to an
      adult have been devised. In 2015, CIPO is newly certified as Specified Rare and
      Intractable Disease which is subsidized from public expense, in Japan. In the
      future, the diagnostic criteria should be appropriately modified by consultation
      with additional researchers to make them more practical and internationally
      applicable.

PMID- 25985647
TI  - [Responses of rhizosphere nitrogen and phosphorus transformations to different
      acid rain intensities in a hilly red soil tea plantation].
AB  - Tea (Camellia sinensis) plantation in hilly red soil region has been long
      impacted by acid deposition, however its effects on nitrogen (N) and phosphorus
      (P) transformations in rhizosphere soils remain unclear. A 25-year old tea
      plantation in a typical hilly red soil region was selected for an in situ
      simulation experiment treated by pH 4.5, pH 3.5, pH 2.5 and control. Rhizosihere
      and bulk soils were collected in the third year from the simulated acid
      deposition experiment. Soil mineral N, available P contents and major enzyme
      activities were analyzed using the chemical extraction and biochemical methods,
      and N and P mineralization rates were estimated using the indoor aerobic
      incubation methods. Our results showed that compared to the control, the
      treatments of pH 4.5, pH 3.5 and pH 2.5, respectively decreased 7.1%, 42.1% and
      49.9% NO3(-)-N, 6.4%, 35.9% and 40.3% mineral N, 10.5%, 41.1% and 46.9% available
      P, 18.7%, 30.1% and 44.7% ammonification rate, 3.6%, 12.7% and 38.8% net N
      mineralization rate, and 31.5%, 41.8% and 63.0% P mineralization rate in
      rhizosphere soils; however, among the 4 treatments, rhizosphere soil
      nitrification rate was not significantly different, the rhizosphere soil urease
      and acid phosphatase activities generally increased with the increasing intensity
      of acid rain (P<0.05). In bulk soil, compared with the control, the treatments of
      pH 4.5, pH 3.5 and pH 2.5 did not cause significant changes in NO3(-)-N, mineral
      N, available P as well as in the rates of nitrification, ammonification, net N
      mineralization and P mineralization. With increasing the acid intensity, the
      rhizosphere effects of NH4+-N, NO3(-)-N, mineral N, ammonification and net N
      mineralization rates were altered from positive to negative effects, those of
      urease and acid phosphatease showed the opposite trends, those of available P and
      P mineralization were negative and that of nitrification was positive. In sum,
      prolonged elevated acid rain could reduce N and P transformation rates, decrease
      their availability, alter their rhizosphere effects, and have impact on nutrient
      cycling in tea plantation.

PMID- 25985648
TI  - [Ecological stoichiometry of soil carbon, nitrogen and phosphorus within soil
      aggregates in tea plantations with different ages].
AB  - This study selected 4 tea plantations with different ages (12-15, 20-22, 30-33
      and >50 year-old) located in Ya' an, Sichuan Province, China to investigate the
      distribution patterns of soil organic carbon (SOC), total nitrogen (TN) and total
      phosphorus (TP) , and to examine the ecological stoichiometric characteristics of
      C, N and P within soil aggregates. The results showed that the coefficients of
      variation of SOC, TN and TP were 17.5%, 16.3% and 9.4%, respectively in the 0-20
      cm soil layer and were 24.0%, 21.0% and 9.2%, respectively in the 20-40 cm soil
      layer. The spatial variation of TP was lower than that of SOC and TN but there
      were significant positive correlations among them. SOC and TN were distributed in
      the small-size aggregates and both of them had the greatest values in the >50
      year-old tea plantation, however, the distribution of TP was relatively uniform
      among aggregates and ages. The coefficients of variation of C/N, C/P, and N/P
      were 9.4%, 14.0% and 14.9%, respectively in the 0-20 cm soil layer and were 7.4%,
      24.9% and 21.8%, respectively in the 20-40 cm soil layer. Variation of C/N was
      lower than that of C/P and N/P. Averaged C/P and N/P values in the small-size
      aggregates were higher than in aggregates of other sizes, and the maximum values
      were in the >50 year-old plantation. C/N, C/P and N/P had good indication for
      soil organic carbon storage.

PMID- 25985650
TI  - [Effects of silicon supply on diurnal variations of physiological properties at
      rice heading stage under elevated UV-B radiation].
AB  - A pot experiment was conducted to investigate the effects of silicon (Si) supply
      on diurnal variations of photosynthesis and transpiration-related physiological
      parameters at rice heading stage under elevated UV-B radiation. The experiment
      was designed with two UV-B radiation levels, i.e. ambient UV-B. (ambient, A) and
      elevated UV-B (elevated by 20%, E), and four Si supply levels, i.e. Sio (control,
      0 kg SiO2 . hm-2), Si, (sodium silicate, 100 kg SiO2 . hm-2), Si2 (sodium
      silicate, 200 kg SiO2 . hm2), Si3 (slag fertilizer, 200 kg SiO2 . hm-2). The
      results showed that, compared with ambient UV-B radiation, elevated UV-B
      radiation decreased the net photosynthesis rate (Pn) , intercellular CO2
      concentration (Ci), transpiration rate (Tr), stomatal conductivity (gs) and water
      use efficiency (WUE) by 11.3%, 5.5%, 10.4%, 20.3% and 6.3%, respectively, in the
      treatment without Si supply (Si, level), and decreased the above parameters by
      3.8%-5.5%, 0.7%-4.8%, 4.0%-8.7%, 7.4%-20.2% and 0.7%-5.9% in the treatments with
      Si supply (Si1, Si2 and Si3 levels) , respectively. Namely, elevated UV-B
      radiation decreased the photosynthesis and transpiration-related physiological
      parameters, but silicon supply could obviously mitigate the depressive effects of
      elevated UV-B radiation. Under elevated UV-B radiation, compared with control
      (Si0 level), silicon supply increased Pn, Ci, gs and WUE by 16.9%-28.0%, 3.5%
      14.3%, 16.8% - 38.7% and 29.0% - 51.2%, respectively, but decreased Tr by 1.9% -
      10.8% in the treatments with Si supply (Si1 , Si2 and Si3 levels). That is,
      silicon supply could mitigate the depressive effects of elevated UV-B radiation
      through significantly increasingnP., CigsgK and WUE, but decreasing T,. However,
      the difference existed in ameliorating the depressive effects of elevated UV-B
      radiation on diurnal variations of physiological parameters among the treatments
      of silicon supply, with the sequence of Si3>Si2>1i >Si0. This study suggested
      that fertilizing slag was helpful not only in recycling industrial wastes, but
      also in effectively mitigating the depressive effects of elevated UV-B radiation
      on photosynthesis and transpiration in rice production.

PMID- 25985649
TI  - [Effects of silicon supply on rice growth and methane emission from paddy soil
      under elevated UV-B radiation].
AB  - A pot experiment was conducted to investigate the effects of silicon supply on
      rice growth and methane (CH4) emission in paddy field under elevated UV-B
      radiation. The experiment was designed with two UV-B radiation levels, i.e.
      ambient UV-B (ambient, A) and elevated UV-B radiation (elevated by 20%, E) ; with
      four silicon supply levels, i.e., Si0 (control, without silicon), Si2 (as sodium
      silicate, 100 kg SiO2 . hm-2), Si2 (as sodium silicate, 200 kg SiO2 hm-2) and Si3
      (as slag fertilizer, 200 kg SiO2 . hm-2). The results indicated that, silicon
      supply obviously alleviated the depressive effect of elevated UV-B radiation on
      rice growth, and increased the tiller numbers, chlorophyll content, and shoot and
      root dry masses. Silicon supply promoted rice growth, which increased with the
      silicon supply level (sodium silicate). Slag fertilizer was better than*sodium
      silicate in promoting rice growth. CH4 flux and accumulated CH4emission were
      obviously increased by elevated UV-B radiation, but significantly decreased by
      silicon application. CH4 emission was reduced with increasing the silicon supply
      level. Under the same silicon supply level, slag fertilizer was better than
      sodium silicate in inhibiting CH4 flux and accumulated CH4 emission. This
      research suggested that fertilizing slag in rice production was helpful not only
      in utilizing industrial wastes, but also in significantly mitigating CH4
      emissions in rice paddy under elevated UV-B radiation.

PMID- 25985651
TI  - [Effects of enhanced UV-B radiation on culm charateristics and lodging index of
      two local rice varieties in Yuanvang terraces under field condition].
AB  - Two local rice varieties (Baijiaolaojing and Yuelianggu) were cultivated in situ
      in Yuanyang terraces, China, in 2012 and 2013 to investigate the effect of
      enhanced UV-B radiation condition (0, 2.5, 5.0 and 7.5 kJ . m2) on internode
      characteristics including length, culm diameter, culm wall thickness from the
      first to the fourth internode, as well as the lodging index. The results showed
      that UV-B radiation had no significant influence on internode length and culm,
      but significanly reduced the culm wall thickness, with that of the fourth
      internode region decreased by 11.6% to 19.6% under 7.5 kJ . m2 UV-B radiation.
      The enhanced UV-B radiation increased the lodging index of rice varieties, making
      them more prone to lodging. The fourth internode had the highest lodging index
      which was higher than the lodging critical value (200). The decrease in culm wall
      thickness due to the enhanced UV-B radiation could be responsible for the
      increasing lodging risk of rice varieties grown in Yuanyang terraces.

PMID- 25985652
TI  - [Effect of light from flowering to maturity stage on dry matter accumulation and
      nutrient absorption of summer maize].
AB  - Using Denghai 605 (DH4605) as the experimental material, shading (S) and
      increasing light (L) treatments from flowering to maturity stage were designed in
      a field experiment to explore effects of light on dry matter accumulation and
      nutrient absorption of summer maize. Results showed that grain yield, dry matter
      accumulation and nutrient absorption decreased significantly after shading but
      increased after increasing light. Yields in S treatment from 2011 to 2013 were
      reduced by 59.4%, 79.0% and 60.6% compared to those in CK, while that in L
      treatment were increased by 16.3%, 12.9% and 6.8%, respectively. The relative N
      and P absorption increased to a certain extent because of the greater effect of
      shading on dry matter accumulation than that of N and P absorption. After
      shading, K absorption of whole plant corn decreased significantly to a greater
      extent than that of dry matter accumulation decrease. The proportion of nutrient
      allocated to grains decreased significantly after shading. Dry matter
      accumulation and N and P absorption rates increased significantly after
      increasing light, and effects of increasing light on N and P absorption were
      greater than that of dry matter accumulation. Nutrient accumulation and the
      proportion allocated to grain increased significantly after increasing light.

PMID- 25985653
TI  - [Responses of non-structural carbohydrate metabolism of cucumber seedlings to
      drought stress and doubled CO2 concentration].
AB  - The effects of doubled CO2 concentration on non-structural carbohydrate
      metabolism of cucumber (Cucumis sativus L. cv. 'Jinyou No.1') seedlings under
      drought stress were investigated. Split plot design was deployed, with two levels
      of CO2 concentrations (ambient CO2 concentration, 380 umol . mol-1, and doubled
      CO2 concentration, 760+/-20 umol . mol-1) in the main plots, and three levels of
      water treatments (control, moderate drought stress, and severe drought stress)
      simulated by PEG 6000 in the split-plots. The results showed that non-structural
      carbohydrates of cucumber leaves, including glucose, fructose, sucrose, and
      stachyose, increased with the doubling of CO2 concentration, which resulted in
      the decreased osmotic potential, improving the drought stress in cucumber
      seedlings. During the drought stress, sucrose synthase, soluble acid invertase
      and al- kaline invertase started with an increase, and followed with a decline in
      the leaves. In the root system, however, soluble acid invertase and alkaline
      invertase increased gradually throughout the whole process, whereas sucrose
      phosphate synthase firstly increased and then decreased. The treatment of doubled
      CO2 enhanced the activity of sucrose synthase, but decreased the activity of
      sucrose phosphate synthase. The synergistic action of the two enzymes and
      invertase accelerated the decomposition of sucrose and inhibited the synthesis of
      sucrose, leading to the accumulation of hexose, which lowered the cellular
      osmotic potential and enhanced the water uptake capacity. In conclusion, doubled
      CO2 concentration could alleviate the adverse effects of drought stress and
      improve the drought tolerance of cucumber seedlings. Such mitigating effect on
      cucumber was more significant under severe drought stress.

PMID- 25985654
TI  - [Physiological response of corn seedlings to changes of wind-sand flow strength].
AB  - Corn seedlings are often harmed by strong wind-sand in the spring in semi-arid
      wind-sand area of west of Northeast China. In order to understand physiological
      response mechanisms of the corn seedlings to wind-sand damage, the changes in MDA
      content, membrane permeability, protective enzymes activities and osmotic
      regulation substances at 0 (CK) , 6, 9, 12, 15 and 18 m . s-1 wind speed (wind
      sand flow strength: 0, 1.00, 28.30, 63.28, 111.82 and 172.93 g . cm-1 . min-1,
      respectively) for 10 min duration were studied during the spring, 2013 in the
      Horqin Sand Land of Inner Mongolia. The results showed that effects of wind-sand
      flow blowing on the RWC of the corn seedling were lighter in the 6-12 m . s-1
      treatments, but the RWC decreased by 19.0% and 18.7% in the 15 m . s-1 and 18 m .
      s-1 treatments compared to the CK, respectively. The MDA content tended to
      decline with increasing the wind-sand flow strength, and decreased by 35.0% and
      39.0% in the 15 m . s-1 and 18 m . s-1 treatments compared to the CK,
      respectively. The membrane permeability increased significantly with increasing
      the wind-sand flow strength, and increased by 191.3% and 187.8% in the 15 m . s-1
      and 18 m . s-1 treatments compared to the CK, respectively. With the increase of
      wind-sand flow strength, SOD activities decreased and changes of CAT activities
      were not significant, only POD activities increased significantly, which played
      an important role in the process of scavenging reactive oxygen species and
      protecting cell membrane against damage. For lighter water stress caused, by wind
      sand flow blowing, proline and soluble sugar did not play any role in osmotic
      adjustment, but the proline content increased by 11.4% and 24.5% in the 15 m . s
      1 and 18 m . s-1 treatments compared to the CK, respectively, which played an
      important role in osmotic adjustment.

PMID- 25985655
TI  - [Effects of air temperature increase and precipitation change on grain yield and
      quality of spring wheat in semiarid area of Northwest China].
AB  - In order to predict effects of climate changing on growth, quality and grain
      yields of spring wheat, a field experiment was conducted to investigate the
      effects of air temperature increases (0  degrees C, 1.0  degrees C, 2.0 degrees 
      C and 3.0 degrees ) and precipitation variations (decrease 20%, unchanging and
      increase 20%) on grain yields, quality, diseases and insect pests of spring wheat
      at the Dingxi Arid Meteorology and Ecological Environment Experimental Station of
      the Institute of Arid Meteorology of China Meteorological Administration (35
      degrees 35' N ,104 degrees 37' E). The results showed that effects of
      precipitation variations on kernel numbers of spring wheat were not significant
      when temperature increased by less than 2.0 degrees  C , but was significant when
      temperature increased by 3.0 degrees  C. Temperature increase enhanced kernel
      numbers, while temperature decrease reduced kernel numbers. The negative effect
      of temperature on thousand-kernel mass of spring wheat increased with increasing
      air temperature. The sterile spikelet of spring wheat response to air temperature
      was quadratic under all precipitation regimes. Compared with control ( no
      temperature increase), the decreases of grain yield of spring wheat when air
      temperature increased by 1.0 degrees C, 2.0 degrees C and 3.0 degrees C under
      each of the three precipitation conditions (decrease 20%, no changing and
      increase 20%) were 12.1%, 24.7% and 42.7%, 8.4%, 15.1% and 21.8%, and 9.0%, 15.5%
      and 22.2%, respectively. The starch content of spring wheat decreased and the
      protein content increased with increasing air temperature. The number of aphids
      increased when air temperature increased by 2.0 degrees C , but decreased when
      air temperature increased by 3.0 degrees CT. The infection rates of rust disease
      increased with increasing air temperature.

PMID- 25985656
TI  - [Nitrogen cycling and balance for wheat in China].
AB  - In this study, the input and output parameters of N for wheat production were
      collected from published literatures and International Plant Nutrition Institute
      in the period of 2000 to 2011 to evaluate N cycling and balances in North China,
      the middle and lower reaches of Yangtze River and Northwest China. The results
      showed that the N fertilizer application rates for each region were 170, 183 and
      150 kg N . hm-2, the amounts of N from the previous crop were 74.6, 15.2 and 8.1
      kg N . hm-2, and from seeds were 4.9, 4.2 and 3.5 kg N . hm-2, respectively. The
      N inputs from symbiotic fixation, atmospheric deposition and irrigation water in
      North China were 15, 12.9 and 9.9 kg N . hm-2, and in the middle and lower
      reaches of Yangtze River were 15, 14.5 and 5.8 kg N . hm-2, and in Northwest
      China were 15, 9.4 and 7.7 kg N . hm-2, respectively. The amounts of N uptake by
      aboveground plant at harvest time in North China, the middle and lower reaches of
      Yangtze River and Northwest China were 174.3, 144.4 and 122.3 kg N . hm-2,
      respectively, and the rates of ammonia volatilization, N20 emission and N
      leaching in North China were 19.9, 2.6 and 11.8 kg N . hm-2, in the middle and
      lower reaches of Yangtze River were 9.4, 2.4 and 15.5 kg N . hm-2, and in
      Northwest China were 3.4, 0.7 and 0 kg N . hm-2, respectively. As a result, the N
      balances in these three regions were all showing surpluses by 78.7, 66.0 and 67.3
      kg N . hm-2. It is therefore necessary to adjust the N fertilizer application
      rates in these three regions to avoid the negative impacts on the environment.

PMID- 25985657
TI  - [Carbon efficiency of double-rice production system in Hunan Province, China].
AB  - Improving the carbon efficiency of crop production systems is one of the
      important ways to realize low-carbon agriculture. A life cycle assessment
      approach and input-output calculation method was applied for a double-rice
      production system in the Hunan Province. Based on statistical data of crop yield
      and investment in the production system in the period from 2004 to 2012, carbon
      emission, carbon absorption, carbon efficiency and their dynamic changes of the
      double rice production systems were estimated. The results showed that the
      average of annual carbon emission from 2004 to 2012 was 656.4 x 10(7) kg CE.
      Carbon emissions from production and transport of fertilizer and pesticide
      accounted for a majority of agricultural input carbon emissions, approximately
      70.0% and 15.9%, respectively. The carbon emission showed a decreasing trend from
      2004 to 2012 in the Hunan Province, with an annual reduction rate of 2.4%, but
      the carbon emission intensity was in a trend of increase. The average of annual
      carbon absorption was 1547.0 x 10(7) kg C. The annual carbon absorption also
      showed a decreasing trend from 2004 to 2012 in Hunan Province, with an average
      annual reduction rate of 1.2%, and the carbon absorption intensity showed a trend
      of increase. Furthermore, production efficiency of carbon showed a slow upward
      trend. The economic efficiency of carbon showed a larger increasing rate with
      time, with an average annual growth rate of 9.9%. Ecological efficiency of carbon
      was stable and low, maintained at about 2.4 kg C . kg-1 CE. It indicated that the
      integrated carbon efficiency of Hunan double rice crop production system improved
      slowly with time and the key to improve the carbon efficiency of double rice
      production systems lies in reducing the rates of nitrogen fertilizer and
      pesticide, and improving their use efficiencies.

PMID- 25985658
TI  - [Effect of long-term fertilization on lignin accumulation in typical subtropical
      upland soil].
AB  - To investigate the effect of long-term fertilization on lignin accumulation and
      clarify its influencing factors in subtropical agricultural upland soils,
      alkaline CuO oxidation and gas chromatography was performed to quantify the
      amount of lignin and its monomers components (V, S and C). The soil samples were
      collected from the fertilization treatments of NPK and NPKS (NPK combined with
      straw) in Huanjiang County, Guangxi Province (limestone soil) and Taoyuan County,
      Hunan Province (red soil). The results showed that NPK had no significant effect
      on the lignin content (Sumvsc) of limestone soil, whereas the content in red soil
      significantly increased by (55 +/- 1)%. For the NPKS treatment, the lignin
      content in limestone and red soil increased by (328 +/- 4)% and (456 +/- 9)%,
      respectively. After the same fertilization treatment, the proportion of cinnamyl
      (C)-type significantly increased in red soil, while a significant increase of
      vanillyl (V)-type monomers occurred in limestone soil, indicating that lignin
      degradation in agricultural soils was monomer specific. Furthermore, the acid-to
      aldehyde ratios of syringyl-type [(Ac/Al)] or vanillyl-type [(Ac/Al)v] monomers
      tended to decrease after long-term fertilization with the higher value for
      limestone soil, suggesting the degree of lignin degradation in limestone was
      higher than that in red soil. Soil organic matter and total nitrogen were not
      correlated with lignin content, but were significantly correlated with the
      composition of VSC monomers. Meanwhile, the available nutrient content in the
      soil (available nitrogen, phosphorus, and potassium) was closely related to the
      contents and components of V, S, and C-type monomers (P<0.05). It indicated that
      the availability of soil nutrition should be considered as a key factor for the
      accumulation of lignin.

PMID- 25985659
TI  - [Impact of tillage practices on microbial biomass carbon in top layer of black
      soils].
AB  - A study was conducted on a long-term (13 years) tillage and rotation experiment
      on black soil in northeast China to determine the effects of tillage, time and
      soil depth on soil microbial biomass carbon (MBC). Tillage systems included no
      tillage (NT), ridge tillage (RT) and mould-board plough (MP). Soil sampling was
      done at 0-5, 5-10 and 10-20 cm depths in June, August and September, 2013, and
      April, 2014 in the corn phase of corn-soybean rotation plots. MBC content was
      measured by the chloroform fumigation extraction (CFE) method. The results showed
      that the MBC content varied with sampling time and soil depth. Soil MBC content
      was the lowest in April for all three tillage systems, and was highest in June
      for MP, and highest in August for NT and RT. At each sampling time, tillage
      system had a significant effect on soil MBC content only in the top 0-5 cm layer.
      The MBC content showed obvious stratification under NT and RT with a higher MBC
      content in the top 0-5 cm layer than under MP. The stratification ratios under NT
      and RT were greatest in September when they were respectively 67.8% and 95.5%
      greater than under MP. Our results showed that soil MBC contents were greatly
      affected by the time and soil depth, and were more apparently accumulated in the
      top layer under NT and RT.

PMID- 25985660
TI  - [Soil C, P and microbial biomass C, P response to different fertilizations in the
      hillslope cropland of purple soil].
AB  - The aim of this study is to explore the changes and coupling characteristics of
      carbon (C), phosphorus (P) and microbial C, P in a hillslope cropland of purple
      soil. The results showed that total organic carbon (TOC) ranged from 90.8 to
      100.8 g . kg-1 under organic fertilizer or straw combined with inorganic
      fertilizer treatments (including N, NP and NPK) as compared with nitrogen (N)
      application only (62.2 g . kg-1). Total phosphorus (TP) ranged from 0.65 to 0.84
      g . kg-1 in organic combined with inorganic fertilization treatments, and that
      under straw combined with inorganic fertilizer treatments was 23%-38% of organic
      fertilizer combined with inorganic fertilization treatments. The microbial
      biomass phosphorus (MBP) under N fertilizer was significantly decreased as
      compared with combined fertilization treatments. The ratios of microbial biomass
      carbon (MBC) to MBP under combined fertilization treatments were between 5 to 26,
      and the TOC/TP ratios under organic fertilizer and straw combined treatments were
      between 92 to 137 and 296 to 653, respectively, while those under N fertilizer
      treatment were 59 and 2000, respectively. The results indicated that combined
      organic and inorganic fertilizers would be helpful for enhancing P availability
      and increasing its potential capacity in purple soil.

PMID- 25985661
TI  - [Effects of irrigation and fertilization on soil microbial properties in summer
      maize field].
AB  - In order to investigate the effects of different irrigation and fertilization on
      soil microbial properties of summer maize field, we used ZN99 with high nitrogen
      use efficiency as the test material. The experiment adopted the split plot design
      which included two irrigation levels (526 mm and 263 mm) as the main plots, three
      fertilizer types (U, M, UM) and two fertilizer levels (N 100 kg . hm-2 and 200 kg
      . hm-2) as the subplots. The results showed that the irrigation level affected
      the regulating effects of fertilizer on soil microbial biomass (carbon and
      nitrogen) and microbial di- versity. The organic fertilizer application must be
      under the sufficient irrigation level to increase the soil MBC (14.3%-33.6%), MBN
      (1.8-2.3 times) and abundance significantly. A moderate rate of irrigation,
      higher rates of organic fertilizer application or organic manure combined with
      inorganic fertilizer could increase the nitrogen-fixation species and quantity of
      Firmicutes, gamma-Proteobacteria and alpha-Proteobacteria in the soil. Under the
      same N level, there was no significant difference of grain yield between organic
      manure and inorganic fertilizer treatments. Considering sustainable production,
      proper organic manure application with moderate irrigation could increase the
      quantity of the soil microbial biomass and microbial diversity, and improve the
      capacity of soil to supply water and nutrients.

PMID- 25985662
TI  - [Effects of tillage type on soil organic carbon and its distribution in oasis
      irrigation area].
AB  - A long-term trial was established in 2005 in the oasis irrigation area to
      determine the impact on the accumulation and distribution of total organic carbon
      (TOC) , particulate organic carbon (POC) and soil microbial biomass carbon (SMBC)
      in 0-90 cm soil layer of 4 types of tillage including conventional tillage (CT),
      fresh raised-bed (FRB), permanent raised-bed (PRB) and zero tillage with control
      traffic on flat field (ZT). The results revealed that the distribution
      characteristics of TOC, POC and SMBC in the soil profile were similar in the four
      tillage treatments, and the carbon content decreased with depth, meanwhile the
      difference among treatments gradually decreased. PRB significantly increased the
      TOC, POC contents and SMBC, which presented in the order of PRB>ZT>FRB>CT in the
      0-90 cm soil layer. In 0-10 cm soil layer, the TOC was increased by 11.1%-24.8%
      for PRB, 9.1%-18.7% for ZT and 7.8%-8.2% for FRB when compared with CT; POC was
      increased by 24.1%-26.5% for PRB, 17.3%-18.7% for ZT, and -8.2% to 10.8% for FRB;
      SMBC was increased by 20.5%-28.3% for PRB, 10.4%-15.2% for ZT and 3.5%-3.7% for
      FRB. TOC had a significant promotion effect on POC. PRB significantly increased
      the proportion of soil POC and enhanced the overall accumulation of organic
      carbon.

PMID- 25985663
TI  - [Effects of different fertilization measures on N2O emission in oil sunflower
      field in irrigation area of upper Yellow River].
AB  - Agricultural soil has become the largest anthropogenic source of atmospheric
      nitrous oxide (N20). To estimate the impacts of long-term combined application of
      organic and inorganic fertilizers on N20 emission in a typical winter wheat-oil
      sunflower cropping system in the Ningxia irrigation area, we measured N20 fluxes
      using the static opaque chamber-gas chromatograph method and monitored the
      seasonal dynamics of related factors. Our results showed that nitrogen addition
      in the previous crop field significantly stimulated N2O emissions during the
      following oil-sunflower cultivation, and the mean fluxes of N300-OM, N240-OM1/2,
      N300 and N240 were (34.16 +/- 9.72), (39.69 +/-10.70), (27.75 +/-9.57) and (26.30
      +/- 8.52) ug . m-2 . h-1, respectively, which were 4.09, 4.75, 3.32 and 3.15
      times of the control groups. The total cumulative N2O emissions of fertilizer
      treatments in growing season was as high as 796.7 to 1242.5 g . hm-2, which was
      2.99 to 4.67 times of the control groups. During the growing season, the rates of
      N2O emission in each month organic and inorganic fertlizers combined treatments
      were similar at high levels. N2O emission in chemical fertilizer treatments
      gradually decreased, and the main period of N2O emission occurred at the
      beginning of growing season. Taking July for example, N2O emission accounted for
      41.3% to 41. 8% of total cumulative amount. The amounts of N20 emission under
      organic and inorganic fertilizers combined treatments were significantly higher
      than under chemical fertilizer treatments. The N2O emissions were not
      significantly different between conventional and optimized applications of
      nitrogen fertilizer under the same fertilizing method, either between N300-OM and
      N240-OM1/2, or between N300 and N240. On account of the drought, N2O emission in
      each treatment was mainly affected by soil moisture. N2O emission had a
      significant positive correlation with soil ammonium nitrogen content under
      combined applications of organic and inorganic fertilizers, but was not
      correlated with soil nitrate nitrogen content under all treatments. This showed
      that adding organic fertilizer could stimulate the NO2 production via increasing
      the soil ammonium nitrogen content.

PMID- 25985664
TI  - [Short-term response of soil CH4 flux to simulated precipitation in a winter
      wheat field on the Loess Plateau, Northwest China].
AB  - To understand the short-term response of soil CH4 flux to different precipitation
      events in a winter wheat field on the Loess Plateau, we conducted precipitation
      simulation experiments during winter wheat jointing stage and summer fallow
      period to measure the soil CH4 flux in 0 to 72 h after precipitation simulation
      of 1 to 32 mm. Results showed that CH4 flux during 0 to 72 h fluctuated at 1 to 8
      mm of precipitation application and peaked at 16 and 32 mm. Cumulative CH4 flux
      after 72 h of precipitation (CH4-C) increased linearly with the precipitation
      amount (P) (wheat jointing stage: CH-C=2.45P-6.09, R2=0.92, P<0.01; summer
      fallow: CH-C=2.43P-4.73, R2 = 0.91, P<0.01). Statistical analysis showed that CH4
      flux was also correlated with soil water content and microbial biomass carbon but
      not with soil temperature. In the long run, small precipitation events (1-8 mm)
      could enhance the intensity of soil CH4 sink and such promoting effect would be
      weakened with further increase in precipitation amount. However, large
      precipitation events (>=16 mm) could change the soil function from CH4 sink to
      source by stimulating the activity of soil methanogens during short-term periods.

PMID- 25985665
TI  - [Effects of land-use conversion from double rice cropping to vegetables on CO2
      and CH4 fluxes in southern China].
AB  - In this study, the CO2 and CH4 fluxes in the first year after land use conversion
      from paddy rice to vegetables were measured by static opaque chamber and gas
      chromatograph (GC) method to investigate the land conversion effects on soil CO2
      and CH4 emissions. Our results showed that the differences in CO2 fluxes depended
      on the vegetable types, growing status and seasons. The CO2 flux from the
      vegetable field was greater than that from the paddy rice field when cowpea was
      planted, but was lower when pepper was planted. The CH4 flux significantly
      decreased from 6.96 mg C . m-2 . h-1 to -0.004 mg C . m-2 . h-1 with the land use
      conversion from rice to vegetables.The net carbon absorption ( CO2 + CH4) of the
      vegetable fields was 543 kg C . hm-2, significantly lower than that (3641 kg C .
      hm-2) of the rice paddies. However, no significant difference was found in their
      global warming impact. In addition, soil carbon content increased in vegetable
      fields compared to the paddy rice fields after a year of conversion, especially
      in the 10-20 cm soil layer.

PMID- 25985666
TI  - [Effects of plastic film mulching on soil CO2 efflux and CO2 concentration in an
      oasis cotton field].
AB  - A field study was conducted to compare soil CO2 efflux and CO2 concentration
      between mulched and non-mulched cotton fields by using closed chamber method and
      diffusion chamber technique. Soil CO2 efflux and CO2 concentration exhibited a
      similar seasonal pattern, decreasing from July to October. Mulched field had a
      lower soil CO2 efflux but a higher CO2 concentration, compared to those of non
      mulched fields. Over the measurement period, cumulative CO2 efflux was 1871.95 kg
      C . hm-2 for mulched field and 2032.81 kg C . hm-2 for non-mulched field. Soil
      CO2 concentration was higher in mulched field (ranging from 5137 to 25945 uL . L
      1) than in non- mulched field (ranging from 2165 to 23986 uL . L-1). The
      correlation coefficients between soil CO2 concentrations at different depths and
      soil CO2 effluxes were 0.60 to 0.73 and 0.57 to 0.75 for the mulched and non
      mulched fields, indicating that soil CO2 concentration played a crucial role in
      soil CO2 emission. The Q10 values were 2.77 and 2.48 for the mulched and non
      mulched fields, respectively, suggesting that CO2 efflux in mulched field was
      more sensitive to the temperature.

PMID- 25985667
TI  - [Effects of superphosphate addition on NH3 and greenhouse gas emissions during
      vegetable waste composting].
AB  - To study the effects of superphosphate (SP) on the NH, and greenhouse gas
      emissions, vegetable waste composting was performed for 27 days using 6 different
      treatments. In addition to the controls, five vegetable waste mixtures (0.77 m3
      each) were treated with different amounts of the SP additive, namely, 5%, 10%,
      15%, 20% and 25%. The ammonia volatilization loss and greenhouse gas emissions
      were measured during composting. Results indicated that the SP additive
      significantly decreased the ammonia volatilization and greenhouse gas emissions
      during vegetable waste composting. The additive reduced the total NH3 emission by
      4.0% to 16.7%. The total greenhouse gas emissions (CO2-eq) of all treatments with
      SP additives were decreased by 10.2% to 20.8%, as compared with the controls. The
      NH3 emission during vegetable waste composting had the highest contribution to
      the greenhouse effect caused by the four different gases. The amount of NH3 (CO2
      eq) from each treatment ranged from 59.90 kg . t-1 to 81.58 kg . t-1; NH3(CO2-eq)
      accounted for 69% to 77% of the total emissions from the four gases. Therefore,
      SP is a cost-effective phosphorus-based fertilizer that can be used as an
      additive during vegetable waste composting to reduce the NH3 and greenhouse gas
      emissions as well as to improve the value of compost as a fertilizer.

PMID- 25985668
TI  - [Effects of long-term tillage and rice straw returning on soil nutrient pools and
      Cd concentration].
AB  - The objective of this study was to assess the effects of tillage and straw
      returning on soil nutrient and its pools, and soil Cd concentration, and to
      identify the strategies for rational tillage and remediation of Cd contaminated
      paddy fields. The experiment was established with no-tillage with straw retention
      (NTS) , rotary tillage with straw incorporation (RTS) , conventional plow tillage
      with straw incorporation (CTS), conventional plow tillage with straw removed (
      CT) from 2005 to 2013. The results indicated that tillage and rice straw
      retention had a great impact on soil properties at 0-10 cm soil depth. The soil
      aeration, and concentrations of soil nutrient and soil Cd increased under CTS,
      CT, and RTS. Due to the shallow plow layers, soil nutrient pools and the Cd
      concentration in rice shoot decreased in long-term tilled soil. Under long-term
      no-tillage, the soil bulk, soil nutrient pools and Cd concentration in rice shoot
      increased, but concentrations of soil nutrients decreased. In addition, rice
      straw returning significantly increased the soil nutrient concentrations, cation
      exchange capacity, depth of plow layer, and soil nutrient pools. However, the Cd
      in the rice straw was also returned to the soil by rice straw returning, which
      would not benefit the remediation of soil Cd. Therefore, it is necessary to
      improve tillage and straw retention practices due to the disadvantages of long
      term continuous single tillage method and rice straw returning practices. Some
      recommended managements (e.g., rotational tillage or subsoiling, reducing straw
      returning amount, and rotational straw returning) could be good options in
      enhancing soil fertility and remedying soil pollution.

PMID- 25985669
TI  - [Spatial variability of soil C/N ratio and its influence factors at a county
      scale in hilly area of Mid-Sichuan Basin, Southwest China].
AB  - Spatial distribution characteristics of soil C/N ratio and its affecting factors
      at a county scale in hilly area of Middle Sichuan Basin were analyzed based on
      field sampling. Result indicated that soil C/N ranged from 4.84 to 21.79, with a
      mean value of 11.93. The coefficient of variation was 26.3%; which suggested soil
      C/N had moderate variability in this study area. The ratio of nugget to sill was
      73.0%, which suggested the spatial variability of soil C/N was determined by both
      structural and random factors, and the random factors played a more important
      role. The soil C/N was higher in northeast and southwest while the central part
      of the study area was characterized by relatively lower values of soil C/N. The
      soil C/N ranged from 10.0 to 13.5 in most parts of the study area. Parent
      material, soil type, topographic factors and land use type had significant
      impacts on soil C/N (P<0.05). Soil C/N showed a significant positive correlation
      with elevation and slope (P<0.05). The soil parent materials were able to explain
      8.7% of soil C/N spatial variability. The explanatory power of soil group,
      subgroup and soil genus were 3.8%, 5.0%, 8.7%, respectively. Topographic factors
      showed the lowest explanatory power of only 0. 8%. However, land use type could
      explain 23.9% of the spatial variability, which suggested that land use type was
      the dominant factor in controlling the spatial variability of soil C/N.

PMID- 25985671
TI  - [Agricultural policies and farming systems: A case study of landscape changes in
      Shizuitou Village in the recent four decades].
AB  - Agricultural policy in China's rural heartland is driving profound changes to
      traditional farming systems. A case study covering four decades mapped and
      recorded farming patterns and processes in Shizuitou Village, a rural village in
      northwest Shanxi. An integrated geospatial methodology from geography and
      anthropology was employed in the case study to record the changing dynamics of
      farming systems in Shizuitou Village to discover the long-term impacts of China's
      agricultural policies on village farming systems. Positive and negative impacts
      of agricultural policies on village farming systems were mapped, inventoried and
      evaluated using Participatory Geographic Information Systems (PGIS). The results
      revealed traditional polycultures are being gradually replaced by industrialized
      monocultures. The driving forces behind these farming changes come from a series
      of government agricultural policies aiming at modernization of farming systems in
      China. The goal of these policies was to spur rapid development of industrial
      agriculture under the guise of modernization but is leading to the decay of
      traditional farming systems in the village that maintained local food security
      with healthy land for hundreds of years. The paper concluded with a
      recommendation that in future, agricultural policy makers should strike a more
      reasonable balance between short-term agricultural profits and long-term farming
      sustainability based on the principles of ecological sustainable development
      under the context of global changes.

PMID- 25985672
TI  - [Cultivated landscape pattern change due to the rice paddy expansion in Northeast
      China: A case study in Fujin].
AB  - On the background of global climate change, agriculture in North China has been
      experiencing substantial modifications to adapt to the ongoing regional warming.
      One of the most significant land use change is the conversation from upland
      cropland to paddy cropland, which is characterized by the dramatic changes of
      agricultural landscape pattern. In this study, we generated land use maps in
      Fujin City in 2000 and 2013 by using Landsat TM imagery, and analyzed the
      landscape pattern changes (cropland composite, special distribution, and patch
      characteristics, etc.) of croplands by using landscape indices and empirical
      approach. The results indicated a rapid cropland increase from 512400
      hm2(reclamation ratio 60.4%) in 2000 to 699300 hm2(reclamation 82.4%) in 2013,
      especially, the paddy cropland proportion in the total cropland increased from
      6.7% to more than half (54.1%) , that is, the agricultural land use mode had
      changed from the initial stage of paddy agriculture to the intermediate stage.
      The reclamation area and common agricultural area showed different paddy
      agriculture development characteristics: in 2000, the paddy field ratios in the
      common agricultural area and reclamation area were similar (5.5% and 8.3%
      respectively); however, in 2013, the paddy field ratio in the common agricultural
      area (33.6%) was significantly lower than that in reclamation area (83.4%). In
      2000, the total number of cropland patches was 2311 in the study, including 1010
      patches from the common agricultural area and 1301 patches from the reclamation
      area. The coefficient of variation (CV) , and shape index (SI) of cropland
      patches in upland cropland were always higher than in paddy cropland. Upland
      cropland had larger mean patch size with the plaque area index above 60% and
      higher connectivity. The patch density of upland cropland was lower than that of
      paddy cropland. In the conversions to the intermediate and later stages of paddy
      agriculture, the patch number of cropland increased rapidly with different rates
      in upland and paddy croplands. The CV of paddy cropland patches increased while
      fluctuated in upland cropland. The SI of paddy cropland increased first and then
      decreased, while that of upland cropland decreased continuously. The mean patch
      sizes of paddy and upland croplands increased and decreased respectively. The
      patch density increased in upland cropland while decreased in paddy cropland. The
      connectivity of upland cropland decreased while that of paddy cropland increased.
      The staggered degree of both cropland types was enhanced from 2000 to 2013. In
      general, the paddy agriculture was becoming the dominated agricultural land use
      mode in the study area while the convesions had different rates in two
      administrative regions (reclamation and common agricultural areas).

PMID- 25985670
TI  - [Impacts of high temperature on maize production and adaptation measures in
      Northeast China].
AB  - Heat stress is one of the major agro-meteorological hazards that affect maize
      production significantly in the farming region of Northeast China (NFR). This
      study analyzed the temporal and spatial changes of the accumulated temperature
      above 30  degrees C (AT) and the accumulated days with the maximum temperature
      above 30  degrees C (AD) in different maize growing phases under global warming.
      It further evaluated the impacts of extreme heat on maize yield in different
      regions, and put forward some adaptation measures to cope with heat stress for
      maize production in NFR. The results showed that during 1961 to 2010, the
      temperature in the maize growing season increased significantly. The maximum
      temperature in flowering phase was much larger than that in the other growing
      phases. Temperature increased at rates of 0. 16, 0. 14, 0.06 and 0.23  degrees C
      every ten years in the whole maize growing season, vegetative growth phase (from
      sowing to 11 days before flowering), flowering phase, and late growth phase (from
      11 days after flowering to maturity), respectively. The AT in the whole maize
      growing season increased in NFR during the last 50 years with the highest in the
      southwest part of NFR, and that in the vegetative growth phase increased faster
      than in the other two phases. The AD in the whole maize growing season increased
      during the last 50 years with the highest in the southwest part of NFR, and that
      in the late growth phase increased faster than in the other two phases. Heat
      stress negatively affected maize yield during the maize growing season,
      particularly in the vegetative growth phase. The heat stress in Songliao Plain
      was much higher in comparison to the other regions. The adaptation measures of
      maize production to heat stress in NFR included optimizing crop structure,
      cultivating high temperature resistant maize varieties, improving maize
      production management and developing the maize production system that could cope
      with disasters.

PMID- 25985673
TI  - [Ecological compensation based on farmers' willingness: A case study of Jingsan
      County in Hubei Province, China].
AB  - Farmland protection is a pressing issue in China' s major agricultural regions
      because of the strategic importance of these regions for national food security.
      This study quantified the appropriate ecological compensation criteria for
      farmland protection by way of estimating farmers' opportunity cost and
      willingness to adopt environment-friendly farming practices. Based on survey data
      collected from Jingsan County, Hubei Province, a Tobit model was constructed to
      identify factors affecting farmers' willingness to accept (WTA). The result
      showed that with appropriate economic compensation for farmland protection, 77.1%
      and 64.7% of the surveyed households were willing to reduce usage of fertilizers
      and pesticides. When the reduced rates of fertilizer and pesticide increased from
      <10% to >50%, farmers' opportunity costs of production respectively increased
      from 1198 and 5850 yuan to 9698 and 9750 yuan per hectare per year, and their WTA
      increased from 4750 and 7313 yuan to 9781 and 12393 yuan per hectare per year.
      Farmers' opportunity cost and WTA in reducing pesticide inputs were larger than
      those in reducing the same rate of fertilizer inputs, and in each case farmers'
      WTA was greater than their opportunity cost. A farm' s distance from township,
      farmers' knowledge about the ecology of farmland, and their expectation to
      improve the ecological environment of farmland had positive, significant effect
      on the farmers' WTA to reducing fertilization, while farmers' education level and
      the overall economic condition of the village had significantly negative effect.
      The proportion of agriculture income, farmers' knowledge about the ecology of
      farmland, and their expectation to improve the ecological environment of farmland
      had positive, significant effect on the farmers' WTA to reducing pesticide, while
      household' cash income and the overall economic condition of the village had
      significantly negative effect.

PMID- 25985674
TI  - [Predicting the impact of climate change in the next 40 years on the yield of
      maize in China].
AB  - Climate change will significantly affect agricultural production in China. The
      combination of the integral regression model and the latest climate projection
      may well assess the impact of future climate change on crop yield. In this paper,
      the correlation model of maize yield and meteorological factors was firstly
      established for different provinces in China by using the integral regression
      method, then the impact of climate change in the next 40 years on China's maize
      production was evaluated combined the latest climate prediction with the reason
      be ing analyzed. The results showed that if the current speeds of maize variety
      improvement and science and technology development were constant, maize yield in
      China would be mainly in an increasing trend of reduction with time in the next
      40 years in a range generally within 5%. Under A2 climate change scenario, the
      region with the most reduction of maize yield would be the Northeast except
      during 2021-2030, and the reduction would be generally in the range of 2.3%-4.2%.
      Maize yield reduction would be also high in the Northwest, Southwest and middle
      and lower reaches of Yangtze River after 2031. Under B2 scenario, the reduction
      of 5.3% in the Northeast in 2031-2040 would be the greatest across all regions.
      Other regions with considerable maize yield reduction would be mainly in the
      Northwest and the Southwest. Reduction in maize yield in North China would be
      small, generally within 2%, under any scenarios, and that in South China would be
      almost unchanged. The reduction of maize yield in most regions would be greater
      under A2 scenario than under B2 scenario except for the period of 2021-2030. The
      effect of the ten day precipitation on maize yield in northern China would be
      almost positive. However, the effect of ten day average temperature on yield of
      maize in all regions would be generally negative. The main reason of maize yield
      reduction was temperature increase in most provinces but precipitation decrease
      in a few provinces. Assessments of the future change of maize yield in China
      based on the different methods were not consistent. Further evaluation needs to
      consider the change of maize variety and scientific and technological progress,
      and to enhance the reliability of evaluation models.

PMID- 25985675
TI  - [Spatiotemporal dynamics of maize water suitability and assessment of
      agricultural drought in Liaoning Province, China from 1981 to 2010].
AB  - Maize water suitability (MWS) model was developed at growth stage scale.
      Frequency and severity of drought were evaluated by combining MWS estimates and
      agricultural meteorological drought indexes. The MWS at each growth stage was
      calculated by using maize observational data and conventional meteorological data
      at 52 sites in Liaoning during the period from 1981 to 2010. Based on the
      climatic trend and abrupt change analysis, spatiotemporal dynamics of MWS were
      investigated. Meanwhile, occurrence of agricultural drought and its severity were
      also estimated. The results showed that the variation of MWS largely differed at
      different growth stages. Climatic abrupt change happened in 1994, 1996 and 1999
      at the stages of emergence to seven leaves (II), jointing to tasseling (IV) and
      physiological maturity to maturity (VI). During the past 30 years, MWS showed an
      obvious increasing trend at the stages of sowing to emergence(I) , seven leaves
      to jointing(III), IV and tasseling to physiological maturity(V), while it showed
      a decreasing trend at the stages of II and VI, and that at VI stage was
      statistically significant. In addition, the climatic trend of MWS showed
      apparently spatial variability. The frequencies of drought at different
      severities varied with maize growth stages. Areas of high variability of MWS were
      located in the Northwest and South of Liaoning at the stages of I , II , III and
      VI, where were also the regions of high frequency of mid- and severe-drought. At
      the stages of IV and V, the frequency of drought was low and only light- and mid
      drought occurred in few areas. In conclusion, the regional mean MWS could be
      capable to reasonably assess the agricultural drought in Liaoning at the regional
      scale.

PMID- 25985676
TI  - [Light and temperature indices during the seeding stage of spring maize in Hetao
      irrigation district, Inner Mongolia, China].
AB  - We collected the experimental dataset of a spring-maize in Hetao irrigation
      district (Bayannaoer, Inner Mongolia) during 2012 and 2013, as well as the crop
      data observed in related agrometeorological stations to investigate the impacts
      of light and temperature variation on maize development during the seedling stage
      to derive adequate light and temperature indices for different suitability.
      Furthermore, polynomial fitting was applied to interpolate the temperature
      indices for each day of the whole seedling period to draw the dynamics of the
      temperature indices and to better characterize its influence on maize development
      during the seedling stage. The results suggested that the emergence and
      development rates increased by 11% and 12%, respectively when the average
      temperature increased 1  degrees C during the sowing-emergence period and
      emergence-jointing period, and the biological lowest temperature was 7.4 and 11.9
      degrees C , respectively. The optimum temperature at the sowing-emergence stage
      ranged from 16.0 to 18.0 degrees C , and the leaf area index at the three-leaf
      stage reached 0.0172 and above. The optimum temperature at the emergence-jointing
      stage ranged from 21.6 to 23.0 degrees 0C , and the photosynthesis/growth of
      plant tissue was positively correlated with the temperature. The leaf area index
      in the jointing period could reach 2.15 and the plant height was 120 cm. At the
      emergence-jointing stage, when the sunshine percentage 74%, or the daily sunshine
      hours >=11.0 h . d-1 , or the total sunshine hours >=540 h, the dry mass of plant
      tissue could

PMID- 25985677
TI  - [Impacts of climate warming on growth period and yield of rice in Northeast China
      during recent two decades].
AB  - By using rice growth period, yield and climate observation data during the recent
      two decades, the impact of climate warming on rice in Northeast China was
      investigated by mathematical statistics methods. The results indicated that in
      the three provinces of Northeast China, the average, maximum and minimum
      temperatures in rice growing season were on the. rise, and the rainfall presented
      a downward trend during 1989-2009. Compared to 1990s, the rice whole growth
      periods of Heilongjiang, Jilin and Liaoning provinces in 2000s were prolonged 14
      d, 4.5 d and 5.1 d, respectively. The increase of temperature in May, June and
      September could extend the rice growth period, while that in July would shorten
      the growth duration. The rice growth duration of registered varieties and
      experiment sites had a similar increasing trend in Northeast China except for the
      Heilongjiang Province, and the extension of registered varieties growth period
      was the main factor causing the prolonged growth period of rice at experiment
      sites. The change in daily average, minimum and maximum temperatures all could
      affect the rice yield in Northeast China. The increasing temperature
      significantly increased the rice yield in Heilongjiang Province, especially in
      the west region of Sanjiang Plain. Except for the south of Liaoning Province,
      rice yields in other regions of Northeast China were promoted by increasing
      temperature. Proper measures for breeding, cultivation and farming, could be
      adopted to fully improve the adaptation of rice to climate warming in Northeast
      China.

PMID- 25985678
TI  - [Effect of climate change on rice irrigation water requirement in Songnen Plain,
      Northeast China].
AB  - Based on meteorological data from China national weather stations and climate
      scenario grid data through regional climate model provided by National Climate
      Center, rice water requirement was calculated by using McCloud model and Penman
      Monteith model combined with crop coefficient approach. Then the rice irrigation
      water requirement was estimated by water balance model, and the changes of rice
      water requirement were analyzed. The results indicated that either in historical
      period or in climate scenario, rice irrigation water requirement contour lines
      during the whole growth period and Lmid period decreased along southwest to
      northeast, and the same irrigation water requirement contour line moved north
      with decade alternation. Rice irrigation water requirement during the whole
      growth period increased fluctuantly with decade alternation at 44.2 mm . 10 a-1
      in historical period and 19.9 mm . 10 a-1 in climate scenario. The increase in
      rice irrigation water requirement during the Lmid period with decade alternation
      was significant in historical period, but not significant in climate scenario.
      Contribution rate of climate change to rice irrigation water requirement would be
      fluctuantly increased with decade alternation in climate scenario. Compared with
      1970s, contribution rates of climate change to rice irrigation water requirement
      were 23.6% in 2000s and 34.4% in 2040s, which increased 14.8 x 10(8) m3
      irrigation water in 2000s and would increase 21.2 x 10(8) m3 irrigation water in
      2040s.

PMID- 25985679
TI  - [Change characteristics of agricultural climate resources in recent 50 years in
      Shandong Province, China].
AB  - Based on the 1961-2010 ground surface data from 90 meteorological stations, this
      paper analyzed the spatiotemporal change characteristics of agricultural climate
      resources (e.g. sunshine hours, thermal resources and water) for the growth
      season of winter wheat and summer maize in Shandong Province. Results indicated
      that temperature indicators showed a significant rising tendency especially in
      the winter wheat growth season. Both evapotranspiration and sunshine hours
      declined obviously, especially for the evapotranspiration in the summer maize
      growth season, while there was no clear change evidence in rainfall and aridity.
      Regarding the spatial distribution characteristics, agro-climatic resources
      presented meridional or zonal increment or decrement in the winter wheat and
      summer maize growth seasons. In different areas, variation features of agro
      climatic resources appeared with distinct differences. In the western Shandong
      area, temperature indicators showed a slight rising tendency while
      evapotranspiration and aridity declined significantly. Sunshine hours decreased
      most significantly in the middle and west southern areas. Precipitation increment
      was relatively obvious in the winter wheat growth season in the middle and east
      southern areas and in the summer maize growth season in the middle and southern
      areas. Thermal resource increases benefited the growth of winter wheat in every
      phase during the growth period. However, it brought high risks of plant diseases
      and hot disaster as well. The decrease of sunshine hours was adverse to crop
      photosynthesis in the growth period while evapotranspiration decrement profited
      the water retention of soil.

PMID- 25985680
TI  - [Agricultural climate regionalization of dryland farming for potato in Yinshan
      based on GIS].
AB  - Based on the meteorology dataset of 34 stations over the Yinshan area through the
      recent 30 years (1982-2010), we investigated the key environmental variables
      influencing potato yield using the correlation and regression methods. Two
      environmental variables, including the mean temperature difference, precipitation
      during the growing season, were selected as the major indexes for determining the
      suitable area for planting potato. Using the GIS-based small grid calculation
      model, we interpolated these two major environmental variables and produced the
      climatic map for potato in Yinshan area. The results showed the high potato yield
      area located in Qianshan and southern Houshan, and the medium-yield division was
      mainly concentrated in the central Houshan and north-west Qianshan, the low-yield
      division was distributed mainly in northern Yinshan. Moreover, this study
      examined the spatial patterns of potato production, and evaluated the stability
      of potato yield by combining the relative variability of potato yield. This study
      could provide valuable references for planting potato in Yinshan area.

PMID- 25985681
TI  - [Nitrogen and water cycling of typical cropland in the North China Plain].
AB  - Intensive fertilization and irrigation associated increasing grain production has
      led to serious groundwater depletion and soil/water pollution in the North China
      Plain (NCP). Intensive agriculture changes the initial mass and energy balance,
      and also results in huge risks to the water/soil resources and food security
      regionally. Based on the research reports on the nitrogen cycle and water cycle
      in typical cropland (winter wheat and summer corn) in the NCP during the past 20
      years, and the meteorological data, field experiments and surveys, we calculated
      the nitrogen cycle and water-cycle for this typical cropland. Annual total
      nitrogen input were 632 kg N . hm-2, including 523 kg N . hm-2 from commercial
      fertilizer, 74 kg N . hm-2 from manure, 23 kg N . hm-2 from atmosphere, and 12 kg
      N . hm-2 from irrigation. All of annual outputs summed to 532 kg N . hm-2
      including 289 kg N . hm-2 for crop, 77 kg N . hm-2 staying in soil profile,
      leaching 104 kg N . hm-2, 52 kg N . hm-2 for ammonia volatilization, 10 kg N . hm
      2 loss in nitrification and denitrification. Uncertainties of the individual
      cases and the summary process lead to the unbalance of nitrogen. For the dominant
      parts of the field water cycle, annual precipitation was 557 mm, irrigation was
      340 mm, while 762 mm was for evapotranspiration and 135 mm was for deep
      percolation. Considering uncertainties in the nitrogen and water cycles, coupled
      experiments based on multi-disciplines would be useful for understanding
      mechanisms for nitrogen and water transfer processes in the soil-plant-atmosphere
      continuum (SPAC) , and the interaction between nitrogen and water, as well as
      determining the critical threshold values for sustainability of soil and water
      resources in the NCP.

PMID- 25985682
TI  - [Evaluation indices of greenhouse gas mitigation technologies in cropland
      ecosystem].
AB  - In spite of the increasing studies on greenhouse gas (GHG) emissions mitigation
      technologies, there is still a lack of systematic indices for evaluation of their
      overall impacts in croplands. In this study, we collected all the indices
      relating to greenhouse gas emissions and analyzed each index following the
      principles of representativeness, objectivity, completeness, dominance and
      operability. Finally, we proposed evaluation indices for mitigation technologies
      based on the current situation of China. Crop yield per unit area was proposed as
      a constrained index, and greenhouse gas emissions intensity, defined as GHG
      emissions per unit of produced yield, was proposed as comprehensive index to
      evaluate the greenhouse effect of various croplands mitigation technologies.
      Calculation of GHG emissions intensity involved yield, change of soil organic
      carbon, direct N2O emissions, paddy CH4 emissions and direct and indirect
      emissions from inputs into croplands. By following these evaluation indices, the
      greenhouse effect of the technologies could be well evaluated, which could
      provide scientific basis for their further adoption.

PMID- 25985683
TI  - [Effects of biochar on soil nutrients leaching and potential mechanisms: A
      review].
AB  - Controlling soil nutrient leaching in farmland ecosystems has been a hotspot in
      the research field of agricultural environment. Biochar has its unique physical
      and chemical properties, playing a significant role in enhancing soil carbon
      storage, improving soil quality and increasing crop yield. As a kind of new
      exogenous material, biochar has the potential in impacting soil nutrient cycling
      directly or indirectly, and has profound influences on soil nutrient leaching.
      This paper analyzed the intrinsic factors affecting how biochar affects soil
      nutrient leaching, such as the physical and chemical properties of biochar, and
      the interaction between biochar and soil organisms. Then the latest literatures
      regarding the external factors, including biochar application rates, soil types,
      depth of soil layer, fertilization conditions and temporal dynamics, through
      which biochar influences soil nutrient (especially nitrogen and phosphorus)
      leaching were reviewed. On that basis, four related action mechanisms were
      clarified, including direct adsorption of nutrients by biochar due to its
      micropore structure or surface charge, influencing nutrient leaching through
      increasing soil water- holding capacity, influencing nutrient cycling through the
      interaction with soil microbes, and preferential transport of absorbed nutrients
      by fine biochar particles. At last future research directions for better
      understanding the interactions between biochar and nutrient leaching in the soil
      were proposed.

PMID- 25985684
TI  - [Characteristics of arbuscular mycorrhizal fungal diversity and functions in
      saline-alkali land].
AB  - Arbuscular mycorrhizal (AM) fungi, widely distributing in various terrestrial
      ecosys- tems, are one of the important functional biotic components in soil
      habitats and play a vital role in improving soil evolution, maintaining soil
      health and sustainable productivity. Saline-alkali soil is a special habitat
      affecting plant growth and grain yield. Under the influence of a series of
      factors, such as human activities on the nature, S and N deposition, ozone,
      greenhouse effect, climate anomalies, and alien species invasions etc., soil
      salinization, biodiversity and functions of saline farmlands may be greatly
      affected, which could consequently influence agricultural production and the
      sustainable development of ecosystems. Followed by an introduction of the
      changing characteristics of saline soil area and the secondary salinization under
      the background of global changes, the present review mainly discussed the
      changing features of diversity and functions of AM fungi in saline habitats,
      summarized the factors influencing AM fungal diversity and functions, and the
      factors' changing characters under the global changes, in order to provide new
      ideas and ways in further elucidating the position, role and function of AM fungi
      in saline soil, and in strengthening saline farmland remediation in response to
      global changes.

PMID- 25985685
TI  - [Optimal allocation of irrigation water resources based on systematical
      strategy].
AB  - With the development of the society and economy, as well as the rapid increase of
      population, more and more water is needed by human, which intensified the
      shortage of water resources. The scarcity of water resources and growing
      competition of water in different water use sectors reduce water availability for
      irrigation, so it is significant to plan and manage irrigation water resources
      scientifically and reasonably for improving water use efficiency (WUE) and
      ensuring food security. Many investigations indicate that WUE can be increased by
      optimization of water use. However, present studies focused primarily on a
      particular aspect or scale, which lack systematic analysis on the problem of
      irrigation water allocation. By summarizing previous related studies, especially
      those based on intelligent algorithms, this article proposed a multi-level, multi
      scale framework for allocating irrigation water, and illustrated the basic theory
      of each component of the framework. Systematical strategy of optimal irrigation
      water allocation can not only control the total volume of irrigation water on the
      time scale, but also reduce water loss on the spatial scale. It could provide
      scientific basis and technical support for improving the irrigation water
      management level and ensuring the food security.

PMID- 25985686
TI  - [Modern surgical tactics in Crohn's disease in coloproctological centre of
      Ukraine].
AB  - Surgical tactics in Crohn's disease (CD) was elaborated by the authors, basing,
      on analysis of modern views on pathogenesis, peculiarities of clinical course,
      possibility of diagnosis and experience of treatment of the disease. It envisages
      a modern diagnosis of the disease, prognostication of the recurrence and
      postoperative complications occurrence, the indications optimization, the choice
      of surgical treatment method Application of the surgical tactics elaborated for
      CD in 121 patients have permitted to improve objective estimation of the disease
      severity, to prognosticate the complications occurrence, to optimize indications
      for surgical treatment and the choice for method o conditionally radical,
      restorational, reconstructive--restoration stages of operative intervention, to
      reduce the disease recurrence rate, postoperative complications and postoperative
      lethality.

PMID- 25985687
TI  - [Gastroduodenal mucosa sensitivity to estrogen in ulcers complicated by
      hemorrhage].
AB  - Expression of alpha-receptors of estrogen (RE) in accordance to
      immunohistochemical (IHC) labeling in gastroduodenal mucosa cells was studied up
      in patients, suffering the ulcer disease and without it. In 4 patients (group I)
      a gastroduodenal mucosa affection was revealed, they were operated on for
      hemorrhage from gastroduodenal ulcers; in 3 patients (group II) gastroduodenal
      mucosa affection was not observed; in 4 patients (group III, control), a mammary
      gland cancer was diagnosed, a positive reaction on alpha-RE was noted. In groups
      I and II the biopsies were studied, obtained from pylorus and gastric fundus, as
      well as from duodenal ampula, and in a group III--obtained from the tumor. In a
      control group a positive labeling of nuclei was revealed in biopsies. In patients
      of groups I and II the alpha-RE expression by cellular nuclei was not revealed,
      but, the lots of positive IHC labeling of cytoplasm in glandular and stromal
      mucosal cells of the investigated gut were noted. Positive IHC labeling of
      cytoplasm for alpha-RE witnesses about sensitivity to them in norma and
      pathological processes. But, a trustworthy difference of alpha-RE expression by
      cellular nuclei was not noted. For confirmation or denial of this hypothesis
      further clinical and IHC investigations are needed.

PMID- 25985688
TI  - [Treatment of patients for stenosing diseases of the esophagus].
AB  - The results of operative treatment of 122 patients for stenosing diseases of the
      esoph- agus during 1993-2014 yrs period were analyzed. The expediency of
      application of the technology proposed was proved.

PMID- 25985689
TI  - [New approaches in surgical treatment of acute paraproctitis].
AB  - The results of treatment of 77 patients, ageing 18-71 yrs old, for an acute
      paraproctitis in 2010-2014 yrs were analyzed. A preventive puncture-flush
      enzymosanation of purulent foci, using immobilized bacterial proteinases
      (imozimase), metrogyl P in conjunction with low-intensive laser irradiation have
      permitted to conduct the optimal preoperative preparation of patients, to improve
      their state, to reduce the local inflammatory reactions intensity significantly.

PMID- 25985690
TI  - [Important esthetic aspects of correction of anterior abdominal wall].
AB  - Effective surgical technology of the umbilicus and the near-umbilicus zone
      formation was proposed, basing on compilation of experience, concerning
      performing of esthetic abdominoplasty in 209 patients. Results were estimated in
      4 groups of patients, in whom a standard and improved methods of umbilicus
      formation were applied.

PMID- 25985691
TI  - [The choice of surgical tactics in incarcerated postoperative abdominal hernias].
AB  - The results of surgical treatment of 82 patients, suffering incarcerated
      postoperative abdominal hernia, were analyzed. Optimal surgical tactics,
      depending on presence of the risk factors for postoperative complications
      occurrence, was proposed. The choice of operative method in patients with
      different operative risk, was substantiated.

PMID- 25985692
TI  - [Comparative analysis of application of highly intensive laser irradiation and
      electrocoagulation during laparoscopic cholecystectomy performed for destructive
      forms of an acute calculous cholecystitis].
AB  - Comparative analysis of results of the laser diode (the wave length 940 nm) and
      elec- trocoagulation application while performing laparoscopic cholecystectomy
      was con- ducted. For an acute calculous cholecystitis 52 patients were operated,
      in whom instead of electrocoagulation the laser was applied, provide for
      reduction of thermal impact on tissues, the complications absence, reduction of
      the patients stationary treatment duration postoperatively from (5.2 +/- 1.2) to
      (4.9 +/- 0.6) days.

PMID- 25985693
TI  - [Clinical and laboratory diagnosis of an acute biliary pancreatitis].
AB  - In 126 patients, suffering an acute biliary pancreatitis (ABP), clinical
      examination was conducted. In 65 patients (1-st group) the isolated
      cholecystolithiasis was noted; in 35 (2-nd group)--cholelithiasis, which did not
      cause obturation of common biliary duct; in 26 (3-rd group)--cholelithiasis,
      which caused the biliary ways obturation (including calculi, which were
      incorporated into the duodenal papilla magna ostium). Clinical course of an ABP
      have differed depending on localization of calculi of extrahepatic biliary ducts.
      In patients, suffering ABP, a biochemical signs of hepatocytes functional
      disorders were observed, impacting the need for hepatoprotector preparations
      inclusion into complex of perioperative conservative therapy. Determination of
      activity of pancreatic alpha-amylase in the blood serum and conduction of the
      ACTIM Pancreatitis test con- stitute the most sensitive and specific methods of
      the ABP biochemical diagnosis.

PMID- 25985694
TI  - [The role of matrix metalloproteinases and their inhibitors in pathogenesis of
      pancreatic pseudocysts].
AB  - The investigation was conducted in 47 patients, operated on for pancreatic
      pseudocysts (PP). Activity of matrix metalloproteinases (MMP-9) and content of
      their tissue inhibitor (TIMP-2) were determined in the blood serum for estimation
      of inflammatory factors, hypoxia severity and state of the pancreatic tissue
      reconstruction. High activity of MMP-9 and TIMP-2 in presence of PP types I and
      II was noted in patients, what, probably, is caused by compensation reaction,
      directed towards inhibition of the collagen system destruction (predominantly of
      collagen type IV) and prevention of further reconstruction of pancreatic
      connective tissue. While progressing of pancreatic fibrosis the MMP-9 activity
      and the TIMP-2 level have lowered in comparison with these indices while its
      absence. In PP type III the MMP-9 activity was by 83.6% higher, than in a control
      group, but, by 51.4 and 35.1% lower, than in PP types I and IV. In all the
      patients endothelial dysfunction with endothelial injury was observed, witnessed
      by significant rising of the VEGF content in the blood serum. It have created
      favorable conditions for pancreatic tissue remodeling while parenchymal defect
      have been constituted by tissue, owing lower level of organization, including a
      cicatricial one. In cases of cellular repeated affection more activation of
      pancreatic stellate cells and enhancement of production of extracellular matrix
      component were noted.

PMID- 25985695
TI  - [Longitudinal shift of left ventricle walls in norm and in dilated
      cardiomyopathy].
AB  - Peculiarities of longitudinal shift of the left ventricle (LV) walls were studied
      in patients in various variants of dilated cardiomyopathy (DCMP). In patients,
      suffering DCMP, the enhancement of the end-diastolic (EDI) and the end-systolic
      (ESI) indexes are noted, as well as of the punch index and expulsion fraction,
      the pulmonary artery hypertension, moderate insufficiency of mitral and tricuspid
      valves. These changes are aggravated in complete blockade of left pedicle of
      atrio-ventricular fascicle (AVF). In cardiac contractions, in normal conditions
      and in DCMP as well, a maximally pronounced longitudinal myocardial shift is
      revealed in basal segments of LV, while cardiac apex remains practically
      immobile. In DCMP a longitudinal shift of the LV myocardium reduces significantly
      while cardiac insufficiency progression. In complete blockade of left pedicle of
      AVF, presented by total reduction of amplitude of longitudinal myocardial shift
      in the LV lateral and posterior walls, aggravation of a mitral valve
      insufficiency (up to 2+) and raising of pressure in pulmonary artery--up to (60.1
      +/- 7.5) mm Hg, further progression of the blood circulation insufficiency were
      noted.

PMID- 25985696
TI  - [Cellular and biochemical contents of suspension of the laundered autologous
      erythrocytes, obtained using a cell saver apparatus].
AB  - Efficacy of autologous blood and residual blood laundering while cardiosurgical
      operations performance in a newborn babies for the inborn heart failures in
      conditions of artificial blood circulation, using a cell saver apparatus, was
      investigated. In accordance to the investigation data obtained, the efficacy of a
      free hemoglobin laundering have constituted 71.6%, proinflammatory interleukin-6-
      95.8%, loss of thrombocytes--85.8%.

PMID- 25985697
TI  - [Efficacy of balloon catheters with antiproliferative cover in patients with
      impairment of arteries of femoral-popliteal segment].
AB  - Results of treatment of 30 patients, suffering affection of arteries of femoro
      popliteal segment, using balloon catheters with treating cover, are analyzed.
      There was proved, that balloon angioplasty, comparing with routine angioplasty,
      provide for significantly better the indices of primary passability of operated
      arteries, as well as reduce the rate of restenosis occurrence in late period.

PMID- 25985698
TI  - [The methods of perioperative correction of the energy-structural
      interrelationships in the organism].
AB  - In a frame of new conceptual approach to the operative risk lowering, the
      innovative methods of a personified perioperative support were presented. Among
      them: dynamical stress-monitoring, antinociceptive narcose potential, methods of
      transfusional and the stress-correction.

PMID- 25985699
TI  - [Morphogenesis of connective tissue in patients with hydronephrosis caused by
      stricture of ureteric-pelvic segment of various etiology].
AB  - In patients, suffering hydronephrosis stages II-III, caused by the ureteric
      pelvic segment (UPS) obstruction due to inborn failures of urinary system, the
      collagen types I and III ratio reduction, and in acquired obstruction--its
      enhancement, are noted in interstitium, renal parenchyma vessels and the UPS
      walls. While obstruction in patients due to inborn failures in vascular basal
      membranes a deficiency of collagen type IV and appearance of nontypical for
      vascular basal membranes intersticial collagen type Il are observed. In the
      acquired UPS, obstruction the, enhancement of content of collagen type IV is
      revealed only. These disorders are mostly pronounced in patients with the disease
      recurrence. There was proposed diagnostic coefficient of ratio between collagens
      types I and III in patients, suffering hydronephrosis, caused by obstruction of
      various etiology. In hydronephrosis, caused by the UPS stricture, the cytokines
      disbalance occurs, impacting processes of collagen formation.

PMID- 25985700
TI  - [Bisegmental anterior interbody spondylodesis, using rigid plates, in surgical
      treatment of cervical vertebral column traumas and diseases].
AB  - Results of surgical treatment of 34 patients, suffering cervical vertebral column
      traumas and diseases, are analyzed. In all the patients bisegmental anterior
      interbody spondylodesis was conducted, using cervical rigid plates and vertical
      cylindrical net implants. The existing and newly obtained information about
      changes in the radiological indices dynamics while the method application by its
      authors is presented. The interbody synostosis was achieved in 82.4% patients in
      1 yr after the operation. The complications rate while the implants application
      have constituted 23.3%, and the total rate of complications--29.1%.

PMID- 25985701
TI  - [The plasty for the hip region sores, using the flap, consisting of M. tensor
      fasciae latae].
AB  - The method of plasty for the hip region sores, based on transposition of proximal
      part of m. tensor fascia latae in content of the flap, using her transsection
      between place of attachment to spina iliaca anterior superior and place of the
      main vascular pedicle entry into the muscle, was proposed, what permits to
      prevent vast mobilization of the muscle and to secure existing in normal
      conditions and formed in pathological conditions anas- tomoses between vascular
      net of the flap and surrounding tissues. The method proposed was successfully
      applied for plasty of the hip region sores of degrees III-IV in 2 patients.

PMID- 25985702
TI  - [Disability due to traumas and diseases of a knee joint].
AB  - The invalidism structure was analyzed for patients, suffering consequences of
      traumas and diseases of a knee joint (KJ). The primary invalidism level because
      of traumas and diseases of a KJ have constituted in 2013 yr 12.4%. The cause of
      invalidism in men is predominantly a one-side gonarthrosis, and in women--a
      bilateral one--due to concurrent aggravating causes (dishormonal changes,
      excessive body mass). The invalidism indices enhancement is caused by absence of
      a dispensary follow-up, insufficient treatment on various stages of the disease
      course, severity and irreversibility of pathological process in a KJ, socio
      economic factors, low rehabilitational potential, prognosticated impossibility to
      conduct a professional-labour rehabilitation in a prepensionable and pensionable
      age.

PMID- 25985703
TI  - [Procalcitonin as a predictor of bacteremia in pediatric patients with
      malignancies and febrile neutropenia].
AB  - Dynamics of procalcitonin level was studied in 75 pediatric patients, in whom on
      back- ground of polychemotherapy conduction for oncological disease bacteremia
      and neutropenia have occurred. Determination of procalcitonin level as a rapidly
      reacting biomarker of generalized infectious process permits to establish its
      progression, to con- duct early diagnosis, to perform timely and adequate
      treatment measures.

PMID- 25985705
TI  - [Peculiarities of heterotopic transplantation of adipose graft enriched by
      allogeneic cryopreserved stem cells from adipose lipoaspirate].
AB  - Possibilities of application of the donor cryoconserved cellular material
      (mesenchymal stem cells, obtained from adipose tissue) for defense of
      transplanted adipose graft from the tissue resorption were studied. The adipose
      graft enrichment, using cryoconserved allogenic mesenchymal multipotent stem
      cells, obtained from adipose tissue, caused activation of destructive
      inflammatory processes in adipose graft, the adipocytes survival worsening, and
      in further--the transplant mass deficiency. We suggest inexpedient to apply in
      clinical practice the donor cryoconserved stem cells for defense of transplanted
      adipose tissue from the tissue resorption.

PMID- 25985704
TI  - [Experimental substantiation of possibility of sanation for purulent enteritis in
      mechanical acute ileus].
AB  - In experiment on the model of mechanical acute ileus (AI) in accordance to
      morphological and microbiological investigations data there was established, that
      in intestinal wall, situated above the obstacle place, purulent enteritis occurs,
      what may constitute the origin of purulent-septic complications after elimination
      of the Al cause. Application of antibacterial preparations permits to slow down
      the progression of destructive processes in the affected intestinal wall.

PMID- 25985706
TI  - Effect of ADRB2 (adrenergic receptor beta2) gene polymorphisms on the occurrence
      of asthma and on the response to nebulized salbutamol in South Indian patients
      with bronchial asthma.
AB  - INTRODUCTION: Genetic mutations in the beta2 receptor could alter its functioning
      and the response to beta2 agonists. The study was done to find out the effect of
      two commonly occurring polymorphisms-Arg16Gly and Gln27Glu, on cause of asthma
      and on response to nebulized salbutamol in South Indian subjects of asthma.
      METHODS: After baseline measurements of Forced Expiratory Volume in 1st second
      (FEV1), Forced Vital Capacity (FVC) and Peak Expiratory Flow Rate (PEFR), five mg
      of nebulized salbutamol was administered and spirometry was repeated. The
      increase in these parameters was calculated and patients were included for
      genotyping if the percentage increase in FEV1 was >=12%. The frequencies of these
      polymorphisms in patients were compared with those of healthy volunteers.
      RESULTS: 112 patients and 127 healthy volunteers were genotyped. The frequencies
      of the polymorphisms were found to be similar to previously published Dravidian
      population frequencies. The frequencies of genotypes in asthmatics were similar
      to healthy volunteers. The increase in FEV1, FVC and PEFR was similar across
      various genotypes and haplotypes in both the polymorphisms. The GG-CG haplotype
      was associated with 3.1 times increased occurrence of asthma (p value = 0.02).
      The G allele of the Arg16Gly polymorphism was associated with lower baseline
      FEV1, FVC and PEFR values, but these were not statistically significant.
      CONCLUSION: The Arg16Gly and Gln27Glu polymorphisms do not determine the
      occurrence of asthma individually, but the GG-CG haplotype is associated with an
      increased risk of asthma. There is no effect of the genotypes on the response to
      nebulized salbutamol.

PMID- 25985708
TI  - The effect of exercise on exhaled nitric oxide depends on allergic
      rhinoconjunctivitis in children.
AB  - OBJECTIVE: Fractional exhaled nitric oxide (FENO) and exercise testing are widely
      used for the evaluation of pediatric asthma. The evidence relating to the effects
      of strenuous exercise on FENO in children is conflicting. Little information is
      available on the association between exercise and FENO in relation to allergic
      rhinoconjunctivitis (AR). We aimed to investigate the effects of AR on children's
      FENO in response to a standardized treadmill exercise test. METHODS: A total of
      124 children with current asthma and 124 non-asthmatic children aged 8-16 years
      were studied. FENO was measured at baseline, at 1 and 30 min after an exercise
      challenge test using the single breath technique with EcoMedics Exhalyzer. A
      structured parental interview, spirometry, serum allergen-specific IgE and skin
      prick tests were performed. RESULTS: Baseline FENO was higher in both asthmatics
      and non-asthmatics with AR than without AR (both p < 0.001). The FENO time trend
      was dependent on AR (p = 0.039), irrespective of asthma (p = 0.876). In children
      with AR, FENO had declined at 1 min by a mean of 6.1 ppb with a 95% confidence
      level of 5.1-7.5 ppb; at 30 min, the reduction was 2.8 (2.5-3.3) ppb. In children
      without AR, at 1 min the decline in FENO was 2.7 (2.1-3.5) ppb and by 30 min post
      exercise it was 1.6 (1.3-2.0) ppb. CONCLUSIONS: The impact of exercise on FENO
      was dependent on the allergic phenotype, regardless of asthma status. FENO
      decreased immediately after exercise, and did not return to baseline level within
      30 min.

PMID- 25985709
TI  - Intestinal microbiota and allergic diseases: A systematic review.
AB  - Evidence suggests that possible imbalances in intestinal microbiota composition
      may be implicated in the occurrence of allergic diseases. Although several
      studies published until 2006 indicated a correlation between microbiota
      composition and allergic symptoms, it has not been possible to distinguish
      protective microorganisms from those associated with increased risk of allergic
      diseases. Therefore, the objective of this study was to review the studies
      published since 2007 that address the intestinal microbiota in allergic diseases.
      Twenty-one studies were identified after excluding those that performed a
      clinical intervention before stool collection. In the early microbiota of
      children who later developed allergies, lower bacterial diversity was observed,
      with a predominance of Firmicutes; a higher count of Bacteroidaceae; a higher
      prevalence of the anaerobic bacteria Bacteroides fragilis, Escherichia coli,
      Clostridium difficile, Bifidobacterium catenulatum, Bifidobacterium bifidum, and
      Bifidobacterium longum; and a lower prevalence of Bifidobacterium adolescentis,
      B. bifidum, and Lactobacillus. In the microbiota of allergic children whose
      intestinal microbiota was assessed at the onset of allergic symptoms, there was a
      higher count of Bacteroides; a lower count of Akkermansia muciniphila,
      Faecalibacterium prausnitzii, and Clostridium; a higher prevalence of B.
      adolescentis; a lower prevalence of B. catenulatum and Staphylococcus aureus; and
      a lower bacterial diversity. 

PMID- 25985707
TI  - Clinical pathway improves pediatrics asthma management in the emergency
      department and reduces admissions.
AB  - OBJECTIVE: Poor adherence to the National Institute of Health (NIH) Asthma
      Guidelines may result in unnecessary admissions for children presenting to the
      emergency department (ED) with exacerbations. We determine the effect of
      implementing an evidence-based ED clinical pathway on corticosteroid and
      bronchodilator administration and imaging utilization, and the subsequent effect
      on hospital admissions in a US ED. METHODS: A prospective, interventional study
      of pediatric (<=21 years) visits to an academic ED between 2011 and 2013 with
      moderate-severe asthma exacerbations has been conducted. A multidisciplinary team
      designed a one-page clinical pathway based on the NIH Guidelines. Nurses,
      respiratory therapists and physicians attended educational sessions prior to the
      pathway implementation. By adjusting for demographics, acuity and ED volume, we
      compared timing and appropriateness of corticosteroid and bronchodilator
      administration, and chest radiograph (CXR) utilization with historical controls
      from 2006 to 2011. Subsequent hospital admission rates were also compared.
      RESULTS: A total of 379 post-intervention visits were compared with 870 controls.
      Corticosteroids were more likely to be administered during post-intervention
      visits (96% vs. 78%, adjusted OR 6.35; 95% CI 3.17-12.73). Post-intervention,
      median time to corticosteroid administration was 45 min faster (RR 0.74; 95% CI
      0.67-0.81) and more patients received corticosteroids within 1 h of arrival (45%
      vs. 18%, OR 3.5; 95% CI 2.50-4.90). More patients received > 1 bronchodilator
      dose within 1 h (36% vs. 24%, OR 1.65; 95% CI 1.23-2.21) and fewer received CXRs
      (27% vs. 42%, OR 0.7; 95% CI 0.52-0.94). There were fewer admissions post
      intervention (13% vs. 21%, OR 0.53; 95% CI 0.37-0.76). CONCLUSION: A clinical
      pathway is associated with improved adherence to NIH Guidelines and,
      subsequently, fewer hospital admissions for pediatric ED patients with asthma
      exacerbations.

PMID- 25985711
TI  - Development of Iron-Chelating Poly(ethylene terephthalate) Packaging for
      Inhibiting Lipid Oxidation in Oil-in-Water Emulsions.
AB  - Foods such as bulk oils, salad dressings, and nutritionally fortified beverages
      that are susceptible to oxidative degradation are often packaged in poly(ethylene
      terephthalate) (PET) bottles with metal chelators added to the food to maintain
      product quality. In the present work, a metal-chelating active packaging material
      is designed and characterized, in which poly(hydroxamic acid) (PHA) metal
      chelating moieties were grafted from the surface of PET. Biomimetic PHA groups
      were grafted in a two-step UV-initiated process without the use of a
      photoinitiator. Surface characterization of the films by attenuated total
      reflective Fourier transform infrared spectroscopy (ATR-FTIR) and scanning
      electron microscopy (SEM) suggested successful grafting and conversion of
      poly(hydroxyethyl acrylate) (PHEA) to PHA chelating moieties from the surface of
      PET. Colorimetric (ferrozine) and inductively coupled plasma mass spectroscopy
      (ICP-MS) assays demonstrated the ability of PET-g-PHA to chelate iron in a low-pH
      (3.0) environment containing a competitive metal chelator (citric acid). Lipid
      oxidation studies demonstrated the antioxidant activity of PET-g-PHA films in
      inhibiting iron-promoted oxidation in an acidified oil-in-water (O/W) emulsion
      model system (pH 3.0). Particle size and zeta-potential analysis indicated that
      the addition of PET-g-PHA films did not affect the physical stability of the
      emulsion system. This work suggests that biomimetic chelating moieties can be
      grafted from PET and effectively inhibit iron-promoted degradation reactions,
      enabling removal of metal-chelating additives from product formulations. 

PMID- 25985710
TI  - Peripheral blood mononuclear cells from severe asthmatic children release lower
      amounts of IL-12 and IL-4 after LPS stimulation.
AB  - INTRODUCTION: Asthma is an inflammatory disorder of the airways associated with
      bronchial hyperresponsiveness, airway obstruction, and increased mucus
      production, with a predominance of type 2 immune response (Th2). According to the
      hygiene hypothesis, exposure to environmental bacterial lipopolysaccharide (LPS)
      may induce a type 1 immune response (Th1), modulating the development of asthma.
      OBJECTIVE: In this study we investigated cytokine production by peripheral blood
      mononuclear cells (PBMC) from children and adolescents with severe asthma, in
      response to LPS stimulation in vitro. MATERIALS AND METHODS: 26 children were
      selected: 13 severe asthmatics and 13 healthy controls, aged between 5 and 18
      years. They were evaluated through routine medical history, physical examination
      and lung function test to diagnose severe asthma. Allergy status was confirmed by
      skin prick test and specific IgE assay. We collected blood samples to analyse in
      vitro LPS-induced cytokines release by PBMC. RESULTS: PBMC from severe asthmatic
      children produced lower levels of IL-12p70 in basal conditions and after 12 and
      24h stimulation with LPS compared to healthy controls. PBMC from severe asthmatic
      children produced lower levels of IL-4 after 24h LPS stimulation compared to
      healthy controls. PBMC from severe asthmatic children produced more levels IL-17
      and IL-10 after stimulus with LPS compared to healthy controls. The release of
      IFN-gamma, IL-5 and TNF-alpha by PBMC from severe asthmatic children was similar
      to healthy controls. CONCLUSION: Our results demonstrate that LPS directly
      influence the cytokine profile of PBMC in children with severe asthma. These
      observations may be potentially helpful in developing new treatment strategies.

PMID- 25985713
TI  - The effect of age on functional outcomes after radical prostatectomy.

PMID- 25985712
TI  - Prognostic reclassification of patients with intermediate-risk metastatic germ
      cell tumors: Implications for clinical practice, trial design, and molecular
      interrogation.
AB  - OBJECTIVES: Approximately one-third of the metastatic germ cell tumors (GCT) in
      patients are classified as intermediate-risk metastatic GCT, and available
      guidelines recommend the same treatment of poor-risk cases. Yet the prognosis of
      these patients is heterogeneous, and consequently refining the intensity of
      treatment is warranted. We aimed to address the heterogeneity of this category by
      providing a proof of principle for reclassification attempt. PATIENTS AND
      METHODS: Data on consecutive patients with intermediate-risk metastatic GCT and
      who received treatment at Fondazione INT Milano in the time frame between
      February 1980 and March 2014 were collected. Cox regression analyses were done,
      evaluating potential prognostic factors for overall survival (OS, primary end
      point) to first-line therapy. Each factor was evaluated in a multivariable model.
      Recursive partitioning was performed to define prognostic risk groups. RESULTS: A
      total of 224 patients were suitable for the present analysis. Median age was 26
      years (interquartile range: 22-31), 11 patients (4.9%) had a retroperitoneal
      primary tumor, 6 yielded seminomatous histology, 85 (37.9%) had lung metastases,
      and 58 (25.9%) had bulky (i.e.,>= 10 cm) retroperitoneal lymph nodes. Patients
      received cisplatin, bleomycin, and etoposide (PEB, n = 199) or vinblastine (PVB,
      n = 23); however, 2 patients received other treatments. Median follow-up was 135
      months (interquartile range: 81-223). Globally, 5-year progression-free survival
      and OS rates were 72.8% (95% CI: 67.1-79.0) and 86.2% (81.7-91.0), respectively.
      In the multivariable model for OS, elevated alfa fetoprotein (AFP) level was the
      only significant prognostic factor (hazard ratio = 1.48, 95% CI: 1.12-1.96). The
      2 separate prognostic groups with differential OS outcomes were identified based
      on the cutoff level of 6,200 IU/ml. The 10-year OS rate was 55.6% (95% CI: 36.6
      84.3), and it was 86.7% (95% CI: 82.0-91.7) for those with AFP levels more than
      (n = 19, 8.5%) and less than (n = 205, 91.5%) the cutoff, respectively.
      CONCLUSIONS: A small fraction of patients with highly elevated AFP levels have an
      OS approximating the poor prognostic category, whereas most of them are close to
      good-risk cases. This might have implications to select outlier patients for
      clinical trials and molecular characterization.

PMID- 25985714
TI  - Analysis of workplace compliance measurements of asbestos by the U.S.
      Occupational Safety and Health Administration (1984-2011).
AB  - The United States Occupational Safety and Health Administration (OSHA) maintains
      the Chemical Exposure Health Data (CEHD) and the Integrated Management
      Information System (IMIS) databases, which contain quantitative and qualitative
      data resulting from compliance inspections conducted from 1984 to 2011. This
      analysis aimed to evaluate trends in workplace asbestos concentrations over time
      and across industries by combining the samples from these two databases. From
      1984 to 2011, personal air samples ranged from 0.001 to 175 f/cc. Asbestos
      compliance sampling data associated with the construction, automotive repair,
      manufacturing, and chemical/petroleum/rubber industries included measurements in
      excess of 10 f/cc, and were above the permissible exposure limit from 2001 to
      2011. The utility of combining the databases was limited by the completeness and
      accuracy of the data recorded. In this analysis, 40% of the data overlapped
      between the two databases. Other limitations included sampling bias associated
      with compliance sampling and errors occurring from user-entered data. A clear
      decreasing trend in both airborne fiber concentrations and the numbers of
      asbestos samples collected parallels historically decreasing trends in the
      consumption of asbestos, and declining mesothelioma incidence rates. Although air
      sampling data indicated that airborne fiber exposure potential was high (>10 f/cc
      for short and long-term samples) in some industries (e.g., construction,
      manufacturing), airborne concentrations have significantly declined over the past
      30 years. Recommendations for improving the existing exposure OSHA databases are
      provided.

PMID- 25985717
TI  - Review of the literature on the use of social media by people with traumatic
      brain injury (TBI).
AB  - PURPOSE: To review the literature relating to use of social media by people with
      a traumatic brain injury (TBI), specifically its use for social engagement,
      information exchange or rehabilitation. METHOD: A systematic review with a
      qualitative meta-synthesis of content themes was conducted. In June 2014, 10
      databases were searched for relevant, peer-reviewed research studies in English
      that related to both TBI and social media. RESULTS: Sixteen studies met the
      inclusion criteria, with FacebookTM and TwitterTM being the most common social
      media represented in the included studies. Content analysis identified three
      major categories of meaning in relation to social media and TBI: (1) risks and
      benefits; (2) barriers and facilitators; and (3) purposes of use of social media.
      A greater emphasis was evident regarding potential risks and apparent barriers to
      social media use, with little focus on facilitators of successful use by people
      with TBI. CONCLUSIONS: Research to date reveals a range of benefits to the use of
      social media by people with TBI however there is little empirical research
      investigating its use. Further research focusing on ways to remove the barriers
      and increase facilitators for the use of social media by people with TBI is
      needed.

PMID- 25985716
TI  - Reliability of measuring hip abductor strength following total knee arthroplasty
      using a hand-held dynamometer.
AB  - PURPOSE: To investigate the test-retest reliability of measuring hip abductor
      strength in patients with total knee arthroplasty (TKA) using a hand-held
      dynamometer (HHD) with two different types of resistance: belt and manual
      resistance. METHOD: Test-retest reliability of 30 subjects (17 female, 13 male,
      71.9 +/- 7.4 years old), 9.2 +/- 2.7 days post TKA was measured using belt and
      therapist resistance. Retest reliability was calculated with intra-class
      coefficients (ICC3,1) and 95% confidence intervals (CI) for both the group
      average and the individual scores. A paired t-test assessed whether a difference
      existed between the belt and therapist methods of resistance. RESULTS: ICCs were
      0.82 and 0.80 for the belt and therapist resisted methods, respectively. Hip
      abductor strength increases of 8 N (14%) for belt resisted and 14 N (17%) for
      therapist resisted measurements of the group average exceeded the 95% CI and may
      represent real change. For individuals, hip abductor strength increases of 33 N
      (72%) (belt resisted) and 57 N (79%) (therapist resisted) could be interpreted as
      real change. CONCLUSIONS: Hip abductor strength can be reliably measured using
      HHD in the clinical setting with the described protocol. Belt resistance
      demonstrated slightly higher test-retest reliability. IMPLICATIONS FOR
      REHABILITATION: Reliable measurement of hip abductor muscle strength in patients
      with TKA is important to ensure deficiencies are addressed in rehabilitation
      programs and function is maximized. Hip abductor strength can be reliably
      measured with a hand-held dynamometer in the clinical setting using manual or
      belt resistance.

PMID- 25985715
TI  - Hepatotoxicity induced by acute and chronic paracetamol overdose in adults. Where
      do we stand?
AB  - Paracetamol (Acetaminophen) poisoning data can reveal the potential deficiencies
      of paracetamol poisoning management guidelines. We conducted a retrospective
      cohort study of patients >18years who were attended in the emergency department
      (ED) of a Spanish tertiary hospital, from 2005 to 2010 for suspected paracetamol
      overdose and who had measurable paracetamol concentrations. 208 patients
      suspected of paracetamol poisoning were identified. The annual incidence in the
      ED increased from 2.0 (95%-CI: 0.2-7.2) cases per 10,000 patients in 2005 to 3.4
      (95%-CI: 1.1-8.8) in 2010. Only 7 of 98 patients (7.14%) with acute poisoning at
      toxic doses showed hepatotoxicity signs, 4 (57.1%) of whom presented acute liver
      failure (ALF) criteria, while 8 of 10 patients (80%) with chronic paracetamol
      poisoning at toxic doses presented hepatotoxicity and 3 (37.5%) with ALF
      criteria. The time required to find medical care was 9.0h for acute poisoning and
      49.6h for chronic poisoning (p<0.001). We conclude that the incidence of
      suspected cases of paracetamol poisoning at our hospital is increasing. The
      majority of toxicity cases, including ALF, associated with the ingestion of
      paracetamol were due to chronic poisoning. This finding constitutes an important
      warning regarding paracetamol chronic poisoning, and clinicians should have a
      higher index of clinical suspicion for this entity. 

PMID- 25985718
TI  - Prevalence of and Sociodemographic Factors Related to Voice Disorders in South
      Korea.
AB  - OBJECTIVES: Studies on the prevalence of and the sociodemographic factors related
      to voice disorders are rare. The purpose of the present study was to analyze the
      prevalence of voice disorders and to identify sociodemographic factors associated
      with an increased risk of voice disorder. METHODS: A cross-sectional study was
      conducted using data from the Korea National Health and Nutrition Examination
      Survey, 2008-2011. Subjects consisted of 19 636 men and women aged >=19 years.
      Sociodemographic factors including occupation, level of education, health status,
      and economic activity were assessed by means of individual interviews, and health
      behaviors such as smoking and alcohol consumption and subjective voice problems
      were assessed with the use of self-administered questionnaires. Laryngology
      interviews and vocal fold examinations were also conducted. RESULTS: The
      prevalence of voice disorders was 8.12% (n = 1594). Subjective perception of the
      presence of voice problems was significantly higher in individuals with vocal
      nodules and vocal polyps (27.7% and 23.0%, respectively; P < 0.001). Among
      sociodemographic factors and health behaviors, voice disorders were found to be
      associated with age, gender, education level, and health status (P < 0.05) but
      were not associated with occupation, household income, smoking, or alcohol
      consumption. CONCLUSIONS: The results of this large epidemiologic study provide
      valuable information regarding the prevalence of voice disorders, and the
      specific data regarding sociodemographic factors and health behaviors suggest
      potential ways of targeting counseling and prevention efforts to control voice
      disorders.

PMID- 25985719
TI  - Genetic diversity and molecular phylogeny of Anaplasma marginale studied
      longitudinally under natural transmission conditions in Rio de Janeiro, Brazil.
AB  - Anaplasma marginale is the most prevalent tick-borne pathogen in cattle in
      tropical and subtropical regions of the world. Major Surface Protein 1a (MSP1a)
      has been found to be a stable genetic marker for identifying A. marginale
      isolates within geographical regions. It is conserved in cattle during infection
      and tick-borne transmission of the pathogen. The aim of the present longitudinal
      study was to determine occurrences of genetic diversity associated with high
      prevalence of A. marginale under natural transmission conditions. Twenty calves
      were evaluated every 3 months during the first year of life. Rickettsemia levels
      due to A. marginale, measured as the number of msp1alphacopies/ml in the blood of
      positive calves, ranged from 2.06*10(3) to 4.36*10(12). The numbers of MSP1a
      tandem repeats among MSP1a tandem repeats were 3 and 6. The predominant msp1alpha
      microsatellite was E, and another MSP1a tandem repeat was found that presented
      genotype G. Nineteen different MSP1a tandem repeats of A. marginale were found
      circulating in animals. The MSP1a tandem repeats 4-63-27 (27.5%), 78-24(2)-25-31
      (n=21.6%) and tau-10(2)-15 (n=17.6%) were the ones most commonly observed. Twenty
      two MSP1a tandem repeats resulted in new sequences with amino acid changes, as
      shown in this study. Thirty sequences were found for the first time in Brazil.
      Glycine, glutamate, serine and alanine amino acids were found at position 20.
      During the study, 80% (16/20) of the animals were infected by more than one
      genotype. Three animals were born infected, with MSP1a tandem repeats 4-63-27, 78
      24(2)-25-31 and tau-10(2)-15, thus indicating occurrence of transplacental
      transmission. In the phylogenetic analysis, 19 different MSP1a tandem repeats of
      A. marginale were found in the cattle, which suggested that many MSP1a tandem
      repeats and high variation in MSP1a were occurring.

PMID- 25985720
TI  - Investigating the first outbreak of oriental theileriosis in cattle in South
      Australia using multiplexed tandem PCR (MT-PCR).
AB  - This study investigated the first outbreak of oriental theileriosis in a herd of
      beef cattle in South Australia using a newly established multiplexed tandem PCR
      (MT-PCR) to identify, differentiate and quantitate the four genotypes (buffeli,
      chitose, ikeda and type 5) of Theileria orientalis recognised to occur in
      Australasia. Following clinical diagnosis of oriental theileriosis (based on
      clinical signs, laboratory findings and post mortem examination), 155 blood
      samples were collected from individual cows (n = 85) and calves (n = 70), and
      tested by MT-PCR. In total, 117 (75.48%) cattle were shown to be test-positive
      for T. orientalis. All four genotypes were detected, and ikeda had the highest
      prevalence (90.6%; 106/117), followed by buffeli (83.8%; 98/117), chitose (18.8%;
      22/117) and type 5 (5.1%; 6/117). Mixed infections with genotypes buffeli and
      ikeda had a higher prevalence (55.5%; 65/117) than any other combination of
      genotypes. The prevalences of buffeli and ikeda were significantly higher
      (P<0.005) than those of chitose and type 5. The average intensity of infection
      with genotype ikeda (329,775 DNA copies) was significantly higher (P<0.0001) than
      buffeli (212,843) and chitose (125,462). This study reinforces the utility of MT
      PCR as a diagnostic tool for rapidly investigating oriental theileriosis
      outbreaks in cattle herds and as a pre-movement screening test for preventing the
      introduction of this disease into non-endemic regions.

PMID- 25985721
TI  - Tick-borne bacteria in Ixodes ricinus collected in southern Norway evaluated by a
      commercial kit and established real-time PCR protocols.
AB  - Ticks are important vectors of human pathogens. The knowledge of disease causing
      agents harboured by ticks in Norway is limited. The focus of this study was (a)
      to detect the bacteria of medical importance in ticks collected from the
      vegetation at locations in the southern part of the country and (b) to evaluate a
      novel commercially available multiplex PCR based method by comparing results with
      conventional established real-time PCR protocols. Borrelia burgdorferi sensu lato
      was confirmed to be the most prevalent pathogen detected (31%) among one hundred
      individually analysed adult ticks. Borrelia miyamotoi, a spirochete associated
      with relapsing fever, was detected in one sample. Anaplasma phagocytophilum was
      found in 4% of the ticks, followed by Rickettsia helvetica which was detected in
      one sample. Similar pathogen prevalence was also detected in 500 ticks analysed
      in pools. This is the first report of the spotted fever group Rickettsia in
      Norway. Francisella tularensis, Bartonella species or Coxiella burnetti was not
      detected. However, due to the low number of ticks analysed, the possible presence
      of these pathogens in the region cannot be ruled out. All isolates were screened
      by at least two different molecular methods for each bacterial target; one
      commercially available multiplex PCR based tick-borne bacteria flow chip system
      (Master Diagnostica) and corresponding real-time PCR protocols. The comparison of
      methods verified that most findings were detected by both methods (71 Borrelia,
      15 Anaplasma and 2 Rickettsia), whereas two additional Borrelia and Anaplasma
      infected samples were detected by the real-time protocols. 

PMID- 25985724
TI  - Controlled delivery of the popular nonsteroidal anti-inflammatory drug,
      paracetamol, from chitosan-g-polyacrylamide microspheres prepared by the emulsion
      crosslinking technique.
AB  - In this paper, chitosan-graft-polyacrylamide (CS-g-PAAm) microspheres as drug
      delivery matrices of paracetamol were prepared by the emulsion crosslinking
      technique, using glutaraldehyde (GA) as a crosslinker. Graft copolymer of
      chitosan with acrylamide was synthesized using cerium (IV) ammonium nitrate
      (CAN). The microspheres formed had average particle sizes in the range of 78-252
      MUm. Paracetamol entrapment efficiency was found to vary between 31.89% and
      72.61%, as determined by UV spectroscopy. Drug release in acidic and phosphate
      buffer solutions (pH 1.2 and 7.4) of the CS-g-PAAm microspheres was influenced by
      formulation factors such as the concentration of CS-g-PAAm, the
      paracetamol/polymer ratio (w/w), and the amount of crosslinker. 

PMID- 25985723
TI  - A "Stepping Stone" Approach for Obtaining Quantum Free Energies of Hydration.
AB  - We present a method which uses DFT (quantum, QM) calculations to improve free
      energies of binding computed with classical force fields (classical, MM). To
      overcome the incomplete overlap of configurational spaces between MM and QM, we
      use a hybrid Monte Carlo approach to generate quickly correct ensembles of
      structures of intermediate states between a MM and a QM/MM description, hence
      taking into account a great fraction of the electronic polarization of the
      quantum system, while being able to use thermodynamic integration to compute the
      free energy of transition between the MM and QM/MM. Then, we perform a final
      transition from QM/MM to full QM using a one-step free energy perturbation
      approach. By using QM/MM as a stepping stone toward the full QM description, we
      find very small convergence errors (<1 kJ/mol) in the transition to full QM. We
      apply this method to compute hydration free energies, and we obtain consistent
      improvements over the MM values for all molecules we used in this study. This
      approach requires large-scale DFT calculations as the full QM systems involved
      the ligands and all waters in their simulation cells, so the linear-scaling DFT
      code ONETEP was used for these calculations. 

PMID- 25985725
TI  - Comparison of the effectiveness of cardiopulmonary resuscitation with standard
      manual chest compressions and the use of TrueCPR and PocketCPR feedback devices.
AB  - BACKGROUND: High effectiveness of chest compressions is an important element of
      cardiopulmonary resuscitation (CPR), improving survival and reducing neurological
      deficits resulting from sudden cardiac arrest. AIM: Evaluation of the
      effectiveness of standard manual chest compressions (SMCC) and CPR with the use
      of two CPR feed-back devices: TrueCPR and PocketCPR. METHODS: 167 paramedics
      participated in the study. The participants were randomised to perform SMCC, CPR
      using the TrueCPR device, and CPR using a smartphone with the PocketCPR
      application in a crossover fashion. RESULTS: Comparison of SMCC, TrueCPR and
      PocketCPR showed differences in the effectiveness of chest compressions (40.3%,
      85.5% and 28.8%, respectively), compression depth (49.5, 56.5 and 50.3 mm,
      respectively), and compression rate (118.5, 105.1, and 89.5 min-1, respectively).
      CONCLUSIONS: During simulated CPR, TrueCPR device significantly increased the
      effectiveness of chest compressions compared to SMCC and the use of PocketCPR
      smartphone application. Further studies are required to confirm these findings in
      clinical practice.

PMID- 25985722
TI  - Global Surgery 2030: evidence and solutions for achieving health, welfare, and
      economic development.

PMID- 25985727
TI  - Combined analysis of myocardial function, viability, and stress perfusion in
      patients with chronic total occlusion in relation to collateral flow.
AB  - BACKGROUND: Indications for revascularisation in chronic total occlusion (CTO) of
      the coronary artery depend on the interplay between myocardial function,
      viability, and ischaemia. The technical feasibility of the procedure often relies
      on the collateral flow to the occluded artery. AIM: To assess the relation
      between the degree of collateral flow and characteristics of the myocardium
      supplied by the oc-cluded artery. METHODS: The study included 54 patients (mean
      age 62 years, 85% males) with CTO referred for cardiovascular magnetic resonance
      (CMR) to assess indications for revascularisation. The presence of well-developed
      collateral flow was defined as a collateral connection grade = 2 and Rentrop
      score = 3. RESULTS: The presence of well-developed collaterals (n = 24, 44%) was
      less likely to be related to systolic dysfunction of the segments supplied by the
      occluded artery (mean wall motion score index 1.31 +/- 0.44 vs. 1.64 +/- 0.67, p
      = 0.04) in comparison to a lack of well-developed collaterals. Patients with well
      developed collaterals had a lower frequency of previous myocar-dial infarction of
      the CTO territory (38% vs. 67%, p = 0.03) with similar frequency of transmural
      infarctions (21% vs. 23%, p = 0.83). They less frequently presented perfusion
      deficits of the CTO area during hyperaemia (42% vs. 70%, p = 0.03) and the size
      of deficits was smaller (median 0.0% [interquartile range 0-12%] vs. 7.5% [0
      15%], p = 0.04). CONCLUSIONS: Myocardial segments supplied by CTO with well
      developed collaterals are less prone to inducible ischaemia, have better systolic
      function, and are less likely to undergo myocardial infarction, in comparison to
      those supplied by CTO with poor collateral circulation. CMR is a non-invasive
      method that can be used for a comprehensive workup of patients be-ing considered
      for CTO revascularisation.

PMID- 25985726
TI  - The relationship between circulating microRNAs and left ventricular mass in
      symptomatic heart failure patients with systolic dysfunction.
AB  - BACKGROUND: In recent years, many microRNAs (miRNAs) were shown to be
      dysregulated in specific tissues playing critical roles in the pathogenesis and
      progression of heart failure (HF). Left ventricular (LV) mass (LVM) has long been
      recognised as an important prognostic marker in systolic HF patients. AIM: We
      hypothesised that circulating miRNAs may be associated with LVM in systolic HF
      patients. The present study aimed to evaluate the relationship between previously
      reported and novel dysregulated circulating miRNAs and echocardiographically
      determined LVM in symptomatic HF patients with LV systolic dysfunction. METHODS:
      Forty-two consecutive patients diagnosed with NYHA II-IV symptomatic systolic HF
      and a control group consisting of 15 age- and sex-matched healthy volunteers were
      enrolled. After labelling extracted RNA, poly-A tails were added. RNAs were later
      hybridised on a GeneChip miRNA 2.0 array. After hybridisation and staining,
      arrays were scanned to determine miRNA expression levels, and differentially
      expressed miRNAs were identified. RESULTS: Eighteen miRNAs were found to be
      upregulated in serum of HF patients, while 11 were demonstrated to be
      downregulated. When the association between dysregulated miRNAs and
      echocardiographic findings was investigated, miR-182 (p = 0.04), miR-200a* (p =
      0.019), and miR-568 (p = 0.023) were found to be inversely correlated with LVM
      index (LVMI), while miR-155 (p = 0.019) and miR-595 (p = 0.04) were determined to
      be positively correlated with LVMI. CONCLUSIONS: The results of our study
      revealed that dysregulated circulating miRNAs were correlated with anatomic
      changes in LV, in terms of LVMI, in symptomatic HF patients with systolic LV
      dysfunction.

PMID- 25985728
TI  - Dose-dependent vascular response following delivery of sirolimus via fast
      releasing, biodegradable polymer stent matrix: an experimental study in the
      porcine coronary model of restenosis.
AB  - BACKGROUND: Fast releasing, rapamycin-eluting stents, although safe, showed
      inferior results with regard to inhibition of restenosis. AIM: Therefore, we
      report vascular effects of a novel, biodegradable polymer stent matrix with
      elevated sirolimus dose and fast release kinetics (ed-frSES, Alex, Balton) in the
      porcine coronary in-stent restenosis model. METHODS: A total of 19 stents were
      implanted with 120% overstretch in the coronary arteries of seven domestic pigs:
      seven ed-frSES with 1.3 MUg/mm2 of sirolimus, eight frSES with 1 MUg/mm2 of
      sirolimus, and eight bare metal stents (BMS). For the following 28 days, coronary
      angiography was performed, animals were sacrificed, and the stented segments
      harvested for histopathological evaluation. RESULTS: In angiography at 28 days
      the late lumen loss was lowest in the elevated dose sirolimus eluting stent (SES)
      (ed-frSES: 0.20 +/- 0.2 vs. frSES: 0.80 +/- 0.5 vs. BMS: 0.96 +/- 0.5 mm, p <
      0.01). This was confirmed in the morphometric evaluation in histopathology as
      represented by a significant and dose-dependent decrease in the percentage area
      of stenosis (ed-frSES: 22.4 +/- 12.7% vs. frSES: 35 +/- 10.7% vs. BMS: 47.5 +/-
      12.5%, p < 0.01). There was no peri-strut inflammation in any of the groups.
      However, the endothelialisation score was numerically not meaningfully decreased
      in ed-frSES (ed-frSES: 2.93 vs. frSES: 3. vs. BMS: 3, p = 0.05). Signs of fibrin
      were also noted in ed-frSES (ed-frSES: 0.4 vs. frSES: 0 vs. BMS: 0, p = 0.05).
      CONCLUSIONS: Sirolimus dose-dependent vascular response was reported. The
      elevated dose, fast releasing SES shows satisfactory vascular healing, similar to
      regular dose, fast release SES, with improved efficacy in restenosis inhibition.

PMID- 25985730
TI  - Does the influence of obesity on prognosis differ in men and women? A study of
      obesity paradox in patients with acute coronary syndrome.
AB  - BACKGROUND: Recent studies have reported the existence of obesity paradox in
      acute coronary syndromes (ACS). However, the occurrence of obesity paradox in men
      and women has not yet been thoroughly investigated, even though both genders
      differ in patterns and incidence of obesity. AIM: Therefore, the aim of this
      study was to investigate whether obesity influence on outcomes of patients with
      ACS varies by gender. METHODS: This retrospective study included 341 patients
      admitted to hospital for treatment due to ACS in 2012. They were classified
      according to the World Health Organisation with use of body mass index (BMI) as
      normal weight, overweight, and obese. All patients received standard discharge
      medication. All-cause mortality was assessed during a mean follow-up time of 212
      +/- 121 days. RESULTS: There were 82 (24%) normal weight, 160 (47%) overweight,
      and 99 (29%) obese patients. There were 252 (73.9%) men. All-cause mortality was
      lower in the obese and overweight vs. normal weight male patients (1.4% vs. 3.3%
      vs. 13.1%, respectively, p = 0.009). There was a trend favouring the normal
      weight and obese vs. overweight women (4.8% vs. 3.6% vs. 17.5%, respectively, p =
      0.103). In the general population, after adjustment, BMI increase by one reduced
      risk by 15.6% (p = 0.015), and obesity reduced risk by 50.8% (p = 0.056). Obesity
      reduced risk for men by 69.4% (p = 0.015), and BMI increase by one reduced risk
      for men by 22% (p = 0.002). BMI and obesity were independent prognostic factors
      in men, whereas no such phenomenon was observed in women. CONCLUSIONS: Only male
      patients seem to contribute to the obesity paradox observed in patients with ACS.
      The obesity paradox does not occur in female patients when considered separately.
      Obesity seems to have a different influence on outcomes in both genders, and this
      might be worthy of further studies.

PMID- 25985729
TI  - Lipoprotein ratios are better than conventional lipid parameters in predicting
      coronary heart disease in Chinese Han people.
AB  - BACKGROUND AND AIM: Dyslipidaemia is the main risk factor for coronary heart
      disease (CHD). Plasma lipid levels are conven-tionally used to predict coronary
      risk globally, but further studies are required to investigate whether the
      lipoprotein ratios are superior to conventional lipid parameters as predictors
      for CHD. METHODS: A hospital-based case-control study consisting of 738 CHD
      patients and 157 control subjects was conducted in a Chinese Han population.
      Demographic characteristics and plasma lipid or apolipoprotein data were
      collected. Univariate and multivariate logistic regression analyses were carried
      out to examine the relationship between the lipoprotein ratios and CHD risk.
      RESULTS: The CHD group had significantly higher age, non-high-density lipoprotein
      cholesterol (non-HDL-C), lipoprotein (a) [Lp(a)], triglyceride (TG)/HDL-C, total
      cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, non
      HDL-C/HDL-C, very low-density lipoprotein cholesterol (VLDL-C)/HDL-C, and
      apolipoprotein B100/apolipoprotein AI (apoB100/apoAI) than the control group (p <
      0.05 for all). Moreover, the prevalence of male sex, smoking, and hypertension in
      the CHD group was significantly higher than in the control group. The results
      from univariate logistic regression analysis showed that the ratios of TC/HDL-C
      (OR 1.135, 95% CI 1.019-1.265), LDL-C/HDL-C (OR 1.216, 95% CI 1.033-1.431), non
      HDL-C/HDL-C (OR 1.135, 95% CI 1.019-1.265), and apoB100/apoAI (OR 1.966, 95% CI
      1.013-3.817) significantly increased the risk for CHD. By multivariate logistic
      regression analysis, the results were not materially altered and each of the four
      ratios was independently associated with CHD after adjustment for non-lipid
      coronary risk factors. ApoB100/apoAI showed the strongest association with CHD in
      both the univariate and multivariate logistic regression analyses. CONCLUSIONS:
      Our data indicate that the lipoprotein ratios are superior to conventional lipid
      parameters as predictors for CHD. Of the ratios, apoB100/apoAI is the best to
      predict CHD risk.

PMID- 25985731
TI  - Influence of a hybrid form of cardiac rehabilitation on exercise tolerance in
      coronary artery disease patients with and without diabetes.
AB  - BACKGROUND: The effectiveness of stationary and ambulatory cardiac rehabilitation
      of patients with coronary artery disease (CAD) and diabetes has been proven by
      some authors, but data concerning the effects of hybrid forms of cardiac
      rehabilitation (HCR) in this population are lacking. A home-based
      telerehabilitation is a promising form of secondary prevention of cardiovascular
      diseases in this group of patients. AIM: The objective of the study was to
      compare the effects of HCR in CAD patients with and without diabetes mellitus
      (DM). The secondary endpoint was the assessment of CAD risk factors like low
      exercise capacity and obesity, in both groups of patients. METHODS: This was a
      retrospective study, which comprised 125 patients with CAD aged 57.31 +/- 5.61
      years referred for HCR. They were assigned to Group D (with diabetes; n = 37) or
      Group C (without diabetes; n = 88). HCR was carried out as a comprehensive
      procedure that included all core components of cardiac rehabilitation according
      to guidelines. Before and after HCR all patients underwent a symptom-limited
      exercise test performed according to the Bruce protocol on a treadmill. RESULTS:
      Before HCR the maximal workload was higher in Group C than in Group D (8.13 +/-
      2.82 METs vs. 6.77 +/- 1.88 METs; p = 0.023), but after HCR the difference was
      not significant. In both groups an increase in the maximal workload after HCR was
      observed (Group D: before HCR 6.81 +/- 1.91 METs, after HCR 8.30 +/- 2.04 METs; p
      < 0.001; Group C: before HCR 8.31 +/- 2.71 METs, after HCR 9.13 +/- 2.87 METs; p
      = 0.001). Resting heart rate, double product, and heart rate recovery 1 (HRR1)
      declined in both groups. No significant differences in changes in exercise test
      parameters between both groups' parameters were found. CONCLUSIONS: HCR was
      effective in patients with DM. The adherence was high. Patients with DM had
      higher rates of obesity and significantly lower exercise tolerance than patients
      without DM. Patients from both groups gained similar benefit from HCR in terms of
      physical capacity, resting heart rate, and heart rate recovery.

PMID- 25985732
TI  - The effect of statin treatment on P-wave characteristics and atrial conduction
      time.
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the effect of statin
      treatment on P-wave morphology, dispersion, and tissue Doppler imaging-derived
      atrial conduction time (PA-TDI), which are known to be predictors of atrial
      fibrillation (AF). METHODS: A total of 132 patients with guideline-directed
      statin indications but no clinical atrial tachyarrhythmias were studied. P-wave
      duration, P-wave dispersion, and P-wave amplitude on surface 12-lead
      electrocardiogram and PA-TDI were evaluated before and after three months of
      statin (either atrovastatin 10-40 mg/d or rosuvastatin 10-20 mg/d) treatment.
      RESULTS: Total and low-density lipoprotein cholesterol were significantly reduced
      after statin therapy. P-wave dispersion significantly decreased from 39.6 +/- 9.4
      to 36.9 +/- 9.6 ms. Statin treatment significantly decreased both the maximum
      (from 1.5 +/- 0.36 to 1.45 +/- 0.33 mV, p = 0.001) and the minimum (from 1.07 +/-
      0.28 to 1.04 +/- 0.27 mV, p = 0.01) P-wave amplitude. The PA-TDI value was found
      to be significantly shorter after statin treatment (121.7 +/- 18.7 vs. 118.7 +/-
      15.8 ms, p = 0.016) CONCLUSIONS: Short-term statin therapy was shown to
      significantly affect P-wave amplitude, P-wave dispersion, and atrial conduction
      time in a broad range of patients without any clinical atrial tachyarrhythmia.

PMID- 25985733
TI  - What do Polish interventional cardiologists know about indications and
      qualification for recanalisation of chronic total coronary artery occlusions?
AB  - BACKGROUND: Chronic total occlusions (CTO) are diagnosed in about 20% of patients
      with significant coronary artery disease. A disproportion between the high
      prevalence of CTOs and low rate of invasive treatment still exists. Technical
      difficulties, clinical uncertainties whether patients benefit from
      recanalisation, and a lack of knowledge of CTO may be responsible for this fact.
      AIM: To assess the knowledge of coronary arteries CTO among Polish interventional
      cardiologists. METHODS: A self-designed questionnaire was used during two major
      Polish invasive cardiology workshops held in 2014. RESULTS: The study included
      113 physicians, mostly cardiologists certified as independent operators. Average
      self-declared efficacy of CTO recanalisation was 63.5%. Most of the respondents
      agreed that the operator involved in the CTO recanalisation program should
      perform at least 30-50 procedures per year. Only 67% stated that before CTO
      revascularisation the evaluation of myocardial viability should be performed with
      dobutamine stress echocardiography as a preferred test. One third of the
      physicians agreed that CTO percutaneous coronary intervention (PCI) should not be
      performed directly after diagnostic angiography, and 51.5% believed that in
      patients with multi-vessel coronary artery disease PCI of CTO should be performed
      first. Multi-slice spiral computed tomography during the qualification and
      planning of the CTO revascularisation, in the opinion of 91% of the responders,
      should not be used before each procedure but could be useful in selected cases.
      CONCLUSIONS: Polish interventional cardiologists remains in compliance with
      current opinions about recanalisation of chronic coronary artery occlusions and
      the consensus of the EuroCTO Club, but there is still an unceasing need for
      further education and promotion of knowledge about CTOs.

PMID- 25985736
TI  - Seasonal and Cyclical Changes in Genetic Composition of the Marine Intertidal
      Rock Pool Copepod Tigriopus brevicornis.
AB  - Tigriopus brevicornis is a marine rock pool copepod widely distributed along
      Atlantic coasts. Due to the absence of a known dispersal mechanism by free
      swimming stages, exchanges between populations over long distances are
      questionable. In order to analyse the evolution of an isolated supralittoral rock
      pool population, sampling of the copepod was performed monthly during 1 year and
      compared to samplings over 5 years in the same rock pool, as well as from other
      rock pools. Using ITS1 analysis, cyclical changes in genetic composition were
      detected. Our results give clear indications concerning the segregation of the
      rock pool population and a lack of gene flow among outside populations. A network
      analysis shows the presence of several shared dominant haplotypes and also
      singletons differing by one mutation point. F(st) analyses indicate that the main
      changes occur in autumn and winter. The few analogies of ITS1 sequences with
      nearby populations may indicate that new migrants must re-colonise the pools from
      surrounding rock crevices in the intertidal habitat where they may have found a
      refuge after bad weather conditions.

PMID- 25985738
TI  - Effective Treatment of Intermediate-Risk Pulmonary Embolism by Manual Thrombus
      Aspiration. A Report of Two Cases.
AB  - Manual thrombectomy, part of the armamentarium of interventional cardiologists,
      might also be considered as an effective and safe alternative to manage
      intermediate/high risk acute PE patients with contraindications to thrombolysis
      or with acute haemodynamic decompensation. We here describe two cases with
      intermediate risk pulmonary embolism and severe hypoxaemia where manual
      thrombectomy with a 10F dedicated catheter was effective and improved clinical
      and haemodynamic parameters. Currently, there's no clear and effective treatment
      for these patients, thus we believe that this therapy, as current ESC guidelines
      suggest, should become a possible alternative to systemic thrombolysis and
      anticoagulant regimen. 

PMID- 25985735
TI  - Pharmacotherapy for alcohol dependence: A stratified approach.
AB  - Alcohol dependence is a common disorder in many societies worldwide, and remains
      difficult to identify and treat. It is also a risk factor for many secondary non
      communicable diseases. Pharmacotherapy is one available treatment option, but
      appears to be underutilised in practice. Major barriers to use of medications in
      this area include lack of clinical guidance and questionable efficacy. However,
      for each medication there appears to be a subpopulation that responds positively,
      and understanding the moderating factors to treatment efficacy is an important
      research goal. Thus, this review provides a narrative regarding potential
      stratification techniques in pharmacological treatment of alcohol dependence,
      with a specific focus on typologies and pharmacogenetics. In addition, we discuss
      the basic background of stratified medicine and recent studies on genetic
      predisposition to alcohol dependence. A growing repository of data exists for
      both approved and non-approved pharmacotherapies, but failure to replicate
      findings, inadequate sample sizes, and insufficient funding has resulted in a
      translational gap. Implementing evidence-based stratified/personalised therapy
      and identifying new therapeutic agents may lead to improved clinical outcomes and
      reduced financial burden. Despite some promising findings to date, much work is
      still required. 

PMID- 25985739
TI  - Accuracy of mechanical torque-limiting devices for dental implants after clinical
      service.
AB  - STATEMENT OF PROBLEM: Limited information is available regarding the accuracy of
      mechanical torque-limiting devices (MTLDs) after their clinical use. PURPOSE: The
      purpose of this study was to determine the accuracy of 2 types of MTLDs (friction
      style and spring-style) after clinical use. MATERIAL AND METHODS: Twenty-seven
      MTLDs in clinical service at The Ohio State University College of Dentistry were
      collected. Thirteen were friction-style and 14 were spring-style. A total of 6
      different dental implant companies were represented (Astra Tech, Zimmer Dental,
      Biomet 3i, Straumann, Nobel Biocare, and Thommen Medical). All MTLDs had been in
      use for at least 6 months without being recalibrated, and all were tested to
      determine their accuracy in delivering target torque values. Statistical analysis
      used nonparametric tests to determine the accuracy of the MTLDs in delivering
      target torque values, and Bonferroni post hoc tests were used to assess pairwise
      comparisons. RESULTS: After clinical service, spring-style MTLDs were
      significantly more accurate than friction-style MTLDs (P<.05). CONCLUSIONS:
      Within the limitations of this study, it was concluded that after clinical
      service, spring-style MTLDs were more accurate than friction-style MTLDs. All
      MTLDs delivered torque values within 10% of the target torque value.

PMID- 25985740
TI  - Digital capture, design, and manufacturing of an extraoral device for a clarinet
      player with Bell's palsy.
AB  - An extraoral device was fabricated to assist a clarinet player with Bell's palsy.
      The device was fabricated by using stereophotogrammetry, digital design, and
      additive manufacturing technologies. 

PMID- 25985737
TI  - C8orf4 negatively regulates self-renewal of liver cancer stem cells via
      suppression of NOTCH2 signalling.
AB  - Liver cancer stem cells (CSCs) harbour self-renewal and differentiation
      properties, accounting for chemotherapy resistance and recurrence. However, the
      molecular mechanisms to sustain liver CSCs remain largely unknown. In this study,
      based on analysis of several hepatocellular carcinoma (HCC) transcriptome
      datasets and our experimental data, we find that C8orf4 is weakly expressed in
      HCC tumours and liver CSCs. C8orf4 attenuates the self-renewal capacity of liver
      CSCs and tumour propagation. We show that NOTCH2 is activated in liver CSCs.
      C8orf4 is located in the cytoplasm of HCC tumour cells and associates with the
      NOTCH2 intracellular domain, which impedes the nuclear translocation of N2ICD.
      C8orf4 deletion causes the nuclear translocation of N2ICD that triggers the
      NOTCH2 signalling, which sustains the stemness of liver CSCs. Finally, NOTCH2
      activation levels are consistent with clinical severity and prognosis of HCC
      patients. Altogether, C8orf4 negatively regulates the self-renewal of liver CSCs
      via suppression of NOTCH2 signalling. 

PMID- 25985743
TI  - Fabrication of a customized tray for preventing fracture of isolated abutment
      teeth in definitive casts.
AB  - Isolated abutment teeth with advanced bone resorption on definitive casts for a
      partial removable dental prosthesis can fracture when the definitive cast is
      removed from the impression or during subsequent laboratory procedures. This
      report describes a technique that avoids fracture of the definitive cast during
      its fabrication. A separating line is formed on the custom tray, which enables
      removal of the definitive cast without fracturing the isolated tooth. In
      addition, if the cervical line is sharp and appears compromised, then the
      impression can be trimmed at the clinical cervical line to enlarge the abutment
      diameter and increase its resistance to fracture without altering the shape of
      critical areas. 

PMID- 25985742
TI  - Clinical study to evaluate the wear of natural enamel antagonist to zirconia and
      metal ceramic crowns.
AB  - STATEMENT OF PROBLEM: Tooth wear is a complex process, which, if not prevented,
      may adversely affect the integrity of the stomatognathic system. Different
      restorative dental materials may affect the amount of wear on natural enamel
      antagonists. PURPOSE: The purpose of this in vivo study was to evaluate and
      compare the wear of enamel opposing natural enamel, zirconia, and metal ceramic
      crowns after 1 year. MATERIAL AND METHODS: Ten participants between 18 and 35
      years of age requiring 2 complete crowns, 1 on either side of maxillary or
      mandibular molar region, and having healthy natural teeth in the opposing arch
      were selected. For each participant, 1 monolithic polished zirconia crown and 1
      glazed metal ceramic crown were fabricated and cemented. To evaluate the wear of
      the antagonistic natural enamel (premolar and molar), polyvinyl siloxane
      impressions were made immediately (baseline) and at 1 year after cementation. The
      wear of natural enamel against natural enamel was evaluated as the control. The
      resulting casts were scanned (using a 3D white light scanner), and 3D software
      was used to calculate the maximum amount of linear wear. RESULTS: One-way
      repeated measures ANOVA was conducted to analyze data. Mean +/-SD occlusal wear
      of the antagonistic enamel 1 year after the cementation of metal ceramic crowns
      was 69.20 +/-4.10 MUm for premolar teeth and 179.70 +/-8.09 MUm for molar teeth,
      whereas for zirconia crowns, it was 42.10 +/-4.30 MUm for premolar teeth and
      127.00 +/-5.03 MUm for molar teeth. Occlusal wear of natural enamel opposing
      natural enamel was 17.30 +/-1.88 MUm in the premolar region and 35.10 +/-2.60 MUm
      in the molar region. The Bonferroni post hoc test revealed that the occlusal wear
      of antagonistic enamel 1 year after the cementation of a metal ceramic crown was
      significantly higher (P<.001) than that of an opposing zirconia crown or natural
      enamel. CONCLUSIONS: Zirconia crowns led to less wear of antagonist enamel than
      metal ceramic crowns, but more than natural enamel.

PMID- 25985734
TI  - Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in
      Patients With Advanced Liver Disease.
AB  - BACKGROUND & AIMS: There are no effective and safe treatments for chronic
      hepatitis C virus (HCV) infection of patients who have advanced liver disease.
      METHODS: In this phase 2, open-label study, we assessed treatment with the NS5A
      inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and
      ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled
      patients with cirrhosis and moderate or severe hepatic impairment who had not
      undergone liver transplantation. Cohort B enrolled patients who had undergone
      liver transplantation: those without cirrhosis; those with cirrhosis and mild,
      moderate, or severe hepatic impairment; and those with fibrosing cholestatic
      hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a
      fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily,
      plus ribavirin. The primary end point was sustained virologic response at 12
      weeks after the end of treatment (SVR12). RESULTS: We enrolled 337 patients, 332
      (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In
      cohort A (nontransplant), SVR12 was achieved by 86%-89% of patients. In cohort B
      (transplant recipients), SVR12 was achieved by 96%-98% of patients without
      cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate
      hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by
      all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12-
      and 24-week groups were similar. Thirteen patients (4%) discontinued the
      ledipasvir and sofosbuvir combination prematurely because of adverse events; 10
      patients died, mainly from complications related to hepatic decompensation.
      CONCLUSION: The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks
      produced high rates of SVR12 in patients with advanced liver disease, including
      those with decompensated cirrhosis before and after liver transplantation.
      ClinTrials.gov: NCT01938430.

PMID- 25985746
TI  - Status and Prospects of Aptamers as Drug Components.
AB  - The unique properties of nucleic acid aptamers and their suitability to
      therapeutic applications have attracted the attention of researchers for more
      than 2 decades. Aptamers exhibit significant advantages relative to antibody
      based therapeutics and can serve dual roles as either the therapeutic agent
      itself or a targeting modality. Despite this intense research interest, aptamers
      have been slow to reach the clinic, partly due to practical limitations that can
      be overcome by rational chemical modifications and ingenious aptamer selection
      approaches. This review highlights the latest efforts to use aptamers in
      therapeutic applications, the key properties of aptamers that can be exploited,
      the aptamers that are currently in clinical trials, as well as speculation on the
      future of aptamers in the field of nanomedicine. 

PMID- 25985747
TI  - Abandonments, Solidarities and Logics of Care: Hospitals as Sites of Sectarian
      Conflict in Gilgit-Baltistan.
AB  - Using data collected over nearly three years of ethnographic fieldwork in the
      Gilgit-Baltistan region of northern Pakistan, my paper explores hospital spaces,
      clinical services and treatment encounters as conduits for the expression and
      propagation of conflictive Shia-Sunni sectarianism. Where my prior research has
      investigated the political etiologies (Hamdy in Am Ethnol 35(4):553-569, 2008)
      associated with Gilgiti women's experiences of childbirth during 'tensions', as
      Shia-Sunni hostilities are locally known, this paper focuses on healthcare
      providers' professional and personal navigations of an episode of conflict whose
      epicentre was at the District Headquarter Hospital, Gilgit-Baltistan's foremost
      government hospital. Through critical evaluation of the impacts of Shia-Sunni
      tensions on the social, administrative and clinical practices and consequences of
      medicine, my paper analyses the complex ways that clinics in crisis serve as
      zones of contact (Pratt in Profession 91:33-40, 1991) and abandonment (Biehl in
      Soc Text 68(19):131-149, 2001; Subjectivity: ethnographic investigations, 2007),
      in which neglect and harm are directed along lines of sectarian affiliation to
      produce vulnerability, spectacular violence and death for healthcare providers
      and patients. 

PMID- 25985750
TI  - Peculiar morphological transitions induced by nanoparticles in polymeric blends:
      retarded relaxation or altered interfacial tension?
AB  - Nanoparticles of different shapes can induce peculiar morphologies in binary
      polymer blends depending on their position. It is envisaged that the increased
      yield stress of the filled phase slows down the relaxation resulting in arresting
      the peculiar morphologies which otherwise is thermodynamically unfavourable due
      to the increased interfacial area. This essentially means that the highly
      irregular structures can be preserved even without altering the interfacial
      tension between the phases! On the other hand, in the case of interfacially
      adsorbed particles, the resulting solid-like interface can also preserve the
      irregular structures. These phenomenal transitions in filled blends are very
      different from the classical copolymer compatibilized polymer blends. Moreover,
      these irregular structures can further pave way in designing conducting polymer
      blends involving conducting nanoparticles and revisiting our understanding of the
      concept of double percolation! 

PMID- 25985744
TI  - Genetic Modification of the Marine-Isolated Yeast Aureobasidium melanogenum P16
      for Efficient Pullulan Production from Inulin.
AB  - In this study, in order to directly and efficiently convert inulin into pullulan,
      the INU1 gene from Kluyveromyces maximum KM was integrated into the genomic DNA
      and actively expressed in the high pullulan producer Aureobasidium melanogenum
      P16 isolated from the mangrove ecosystem. After the ability to produce pullulan
      from inulin by different transformants was examined, it was found that the
      recombinant strain EI36, one of the transformants, produced 40.92 U/ml of
      inulinase activity while its wild-type strain P16 only yielded 7.57 U/ml of
      inulinase activity. Most (99.27 %) of the inulinase produced by the recombinant
      strain EI36 was secreted into the culture. During the 10-l fermentation, 70.57 +/
      1.3 g/l of pullulan in the fermented medium was attained from inulin (138.0 g/l)
      within 108 h, high inulinase activity (42.03 U/ml) was produced within 60 h, the
      added inulin was actively hydrolyzed by the secreted inulinase, and most of the
      reducing sugars were used by the recombinant strain EI36. This confirmed that the
      genetically engineered yeast of A. melanogenum strain P16 was suitable for direct
      pullulan production from inulin.

PMID- 25985741
TI  - Fracture load of ceramic restorations after fatigue loading.
AB  - STATEMENT OF PROBLEM: A clinician must decide what ceramic coping and veneer
      material to prescribe based on the amount of tooth reduction possible and the
      desired esthetic outcome of the restoration. PURPOSE: The purpose of this in
      vitro study was to compare the fracture strength of monolithic and bilayered
      lithium disilicate (IPS e.max) and zirconia (LAVA) crowns at clinically relevant
      thicknesses after load cycling. MATERIAL AND METHODS: Crowns (n=8) were
      fabricated from 6 groups: 1.2-mm monolithic lithium disilicate, 1.5-mm monolithic
      lithium disilicate, 1.5-mm bilayered lithium disilicate with hand-layered veneer,
      0.6 mm monolithic zirconia, 1.2-mm bilayered zirconia with hand-layered veneer,
      and 1.2-mm bilayered zirconia with milled veneer (dimension represents thickness
      at the occlusal pit). Crowns were cemented to identical milled resin dies with
      resin-modified glass ionomer cement. Cemented crowns were stored at 37 degrees C
      for 24 hours and load cycled for 200,000 cycles at 25 N at a rate of 40
      cycles/minute. The ultimate fracture load for each specimen was measured in a
      universal testing machine. Data were analyzed with a 1-way ANOVA and Tukey honest
      significant difference post hoc analysis (alpha=.05). RESULTS: Mean +/-SD
      fracture load values were 1465 +/-330 N for monolithic lithium disilicate (1.2-mm
      thickness) and 2027 +/-365 N (1.5-mm thickness) and 1732 +/-315 N for bilayered
      hand-veneered lithium disilicate (1.5-mm thickness). Fracture loads were 1669 +/
      311 N for monolithic zirconia crowns (0.6mm thickness), 2625 +/-300 N for
      zirconia milled-veneered (1.2-mm thickness), and 2655 +/-590N for zirconia hand
      veneered crowns (1.2mm thickness). One-way ANOVA showed a statistically
      significant difference among the groups (P<.01). Veneered zirconia crowns showed
      the highest fracture strength, 1.2-mm hand veneered zirconia was similar to that
      of 1.5-mm monolithic zirconia, and all other groups were not statistically
      different. CONCLUSIONS: Crowns of 1.2-mm bilayered zirconia had higher fracture
      loads than 0.6-mm zirconia or 1.2-mm lithium disilicate monolithic crowns.

PMID- 25985749
TI  - OGTT and random plasma glucose in the prediction of type 1 diabetes and time to
      diagnosis.
AB  - AIMS/HYPOTHESIS: We assessed the utility of the OGTT and random plasma glucose
      concentrations in predicting the time to diagnosis of type 1 diabetes. METHODS: A
      population-derived cohort of 14,876 newborns with HLA-conferred risk of type 1
      diabetes were invited to regular follow-up for islet autoantibodies. When two or
      more autoantibodies were detected, an OGTT was performed once a year and random
      plasma glucose analysed twice a year. During follow-up, 567 children developed
      multiple autoantibodies, 255 (45%) of whom were diagnosed with type 1 diabetes,
      while 312 remained non-diabetic by December 2011. RESULTS: Impaired fasting
      glucose (IFG) and impaired glucose tolerance (IGT) were risk factors for type 1
      diabetes (HR 3.2 [95% CI 1.5, 7.0] and 8.3 [95% CI 6.0, 11.5], respectively).
      When a random plasma glucose value >= 7.8 mmol/l was observed, the HR for
      diabetes was 6.0 (95% CI 4.3, 8.6). The median time to diagnosis after the
      detection of IFG was 5.2 years (interquartile range [IQR] 3.4, 6.3); after IGT,
      0.7 years (IQR 0.3, 1.9); and, after a random plasma glucose >= 7.8 mmol/l, 1.0
      years (IQR 0.3, 1.5). In a retrospective analysis, both OGTT-derived 2 h plasma
      glucose and random plasma glucose started to increase 1.5 years before diagnosis
      (p < 0.001 and p = 0.004, respectively). CONCLUSIONS/INTERPRETATION: Dysglycaemia
      detected in an OGTT or based on random plasma glucose is a useful marker in the
      prediction of time to onset of type 1 diabetes in high-risk children. Random
      plasma glucose is a simple and low-cost measurement with comparable predictive
      characteristics to that of OGTT-derived 2 h glucose.

PMID- 25985748
TI  - Infrared thermographic assessment of changes in skin temperature during
      hypoglycaemia in patients with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Hypoglycaemia is associated with reduced skin temperature (Ts).
      We studied whether infrared thermography can detect Ts changes during
      hypoglycaemia in patients with type 1 diabetes and how the Ts response differs
      between patients with normal hypoglycaemia awareness and hypoglycaemia
      unawareness. METHODS: Twenty-four patients with type 1 diabetes (ten aware, 14
      unaware) were studied during normoglycaemia (5.0-6.0 mmol/l), hypoglycaemia (2.0
      2.5 mmol/l) and during recovery from hypoglycaemia (5.0-6.0 mmol/l) using
      hyperinsulinaemic glucose clamping. During each 1 h phase, Ts was measured twice
      by infrared thermography imaging in pre-defined areas (nose, glabella and the
      five left fingertips), symptoms of hypoglycaemia were scored and blood was
      sampled. RESULTS: Ts decreased during hypoglycaemia on the nose and glabella. The
      highest decrements were recorded on the nose (aware: -2.6  degrees C, unaware: 
      1.1  degrees C). In aware patients, the differences in temperature were
      statistically significant on both nose and glabella, whereas there was only a
      trend in the unaware group. There was a significant difference in hypoglycaemia
      induced temperature changes between the groups. Patients in the aware group had
      higher hypoglycaemia symptom scores and higher adrenaline (epinephrine) levels
      during hypoglycaemia. CONCLUSIONS/INTERPRETATION: The hypoglycaemia-associated
      decrement in Ts can be assessed by infrared thermography and is larger in
      patients with normal hypoglycaemia awareness compared with unaware patients.

PMID- 25985751
TI  - Stemming the Tide: Infectious Complications After Prostate Biopsy.

PMID- 25985752
TI  - An elastography analytical method for the rapid detection of endotoxin.
AB  - We present a flexible analytical method for the study of coagulation systems by
      monitoring elastography (EG). The rapid detection of endotoxin is achieved by the
      EG analysis of endotoxin-induced limulus amebocyte lysate coagulation. This
      method is superior to other methods using the same reagents in not only
      sensitivity but also detecting time. 

PMID- 25985745
TI  - Co-occurrence of musk fragrances and UV-filters in seafood and macroalgae
      collected in European hotspots.
AB  - In the last decades, awareness regarding personal care products (PCP), i.e.
      synthetic organic chemicals frequently used in cosmetic and hygienic products,
      has become a forward-looking issue, due to their persistency in the environment
      and their potential multi-organ toxicity in both human and wildlife. Seafood is
      one of the most significant food commodities in the world and, certainly, one of
      the most prone to bioaccumulation of PCP, what can consequently lead to human
      exposure, especially for coastal population, where its consumption is more
      marked. The aim of this work was to evaluate the co-occurrence of musk fragrances
      and UV-filters in both seafood and macroalgae collected in different European
      hotspots (areas with high levels of pollution, highly populated and near
      wastewater treatment plants). Despite the fact that UV-filters were detected in
      three different kind of samples (mussel, mullet, and clam), in all cases they
      were below the limit of quantification. Galaxolide (HHCB) and tonalide (AHTN)
      were the musk fragrances most frequently detected and quantified in samples from
      the European hotspots. Cashmeran (DPMI) was also detected in most samples but
      only quantified in two of them (flounder/herring and mullet). The highest levels
      of HHCB and AHTN were found in mussels from Po estuary. 

PMID- 25985753
TI  - Epac2-deficiency leads to more severe retinal swelling, glial reactivity and
      oxidative stress in transient middle cerebral artery occlusion induced ischemic
      retinopathy.
AB  - Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell
      reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are cAMP
      mediators playing important roles in maintenance of endothelial barrier and
      neuronal functions. To investigate the roles of Epacs in the pathogenesis of
      ischemic retinopathy, transient middle cerebral artery occlusion (tMCAO) was
      performed on Epac1-deficient (Epac1 (-/-)) mice, Epac2-deficient (Epac2 (-/-))
      mice, and their wild type counterparts (Epac1 (+/+) and Epac2 (+/+)). Two-hour
      occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion
      injury to the retina. After tMCAO, the contralateral retinae displayed similar
      morphology between different genotypes. Neuronal loss, retinal edema and increase
      in immunoreactivity for aquaporin 4 (AQP4), glial fibrillary acidic protein
      (GFAP), peroxiredoxin 6 (Prx6) were observed in ipsilateral retinae. Epac2 (-/-)
      ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer,
      increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6
      than those of Epac2 (+/+). However, Epac1 (-/-) ipsilateral retinae displayed
      similar pathology as those in Epac1 (+/+) mice. Our observations suggest that
      Epac2-deficiency led to more severe ischemic retinopathy after retinal
      ischemia/reperfusion injury. 

PMID- 25985754
TI  - Translational Medicine Center of West China Hospital.

PMID- 25985755
TI  - The role of the microenvironment on the fate of adult stem cells.
AB  - Adult stem cells (SCs) exist in all tissues that promote tissue growth,
      regeneration, and healing throughout life. The SC niche in which they reside
      provides signals that direct them to proliferate, differentiate, or remain
      dormant; these factors include neighboring cells, the extracellular matrix,
      soluble molecules, and physical stimuli. In disease and aging states, stable or
      transitory changes in the microenvironment can directly cause SC activation or
      inhibition in tissue healing as well as functional regulation. Here, we discuss
      the microenvironmental regulation of the behavior of SC and focus on plasticity
      approaches by which various environmental factors can enhance the function of SCs
      and more effectively direct the fate of SCs. 

PMID- 25985756
TI  - Building biological foundries for next-generation synthetic biology.
AB  - Synthetic biology is an interdisciplinary field that takes top-down approaches to
      understand and engineer biological systems through design-build-test cycles. A
      number of advances in this relatively young field have greatly accelerated such
      engineering cycles. Specifically, various innovative tools were developed for in
      silico biosystems design, DNA de novo synthesis and assembly, construct
      verification, as well as metabolite analysis, which have laid a solid foundation
      for building biological foundries for rapid prototyping of improved or novel
      biosystems. This review summarizes the state-of-the-art technologies for
      synthetic biology and discusses the challenges to establish such biological
      foundries. 

PMID- 25985757
TI  - Association of serum adiponectin with asthma and pulmonary function in the
      Japanese population.
AB  - Conflicting findings have been reported regarding the role of adiponectin in
      asthma. The aim of this study was to evaluate the association of adiponectin with
      pulmonary functions and asthma in the Japanese population. First, among a general
      population that participated in a previous study (group 1), we selected 329
      subjects after excluding those with asthma, chronic obstructive pulmonary
      disease, and a smoking history and examined the associations of the serum total
      adiponectin levels with pulmonary functions. In a second cohort (group 2)
      consisting of 61 asthmatic patients and 175 control non-asthmatic subjects, we
      examined the associations between asthma and the levels of total, high (HMW),
      middle (MMW) and low (LMW) molecular weight adiponectin isoforms as well as the
      ratio of each isoform to total adiponectin level. Although the total adiponectin
      levels were not significantly different between the asthmatic and control
      subjects in group 2, the levels were significantly and positively associated with
      the forced expiratory volume in 1 s after adjustments for confounding factors (P
      < 0.05) in women in group 1. In group 2, the LMW adiponectin level was
      significantly higher and the MMW/total adiponectin ratio was significantly lower
      among the asthmatic subjects than among the control subjects after adjustments
      for confounding factors in both sexes (P < 0.05). The present study showed that a
      low total adiponectin level may lead to airway narrowing compatible with
      asthmatic airways in women, and higher LMW adiponectin levels and lower MMW/total
      adiponectin ratio are significantly associated with current asthma in both sexes.

PMID- 25985758
TI  - The general entity of life: a cybernetic approach.
AB  - Life, not only in the well-known context of biochemical metabolism but also in
      the context of hypothetical life synthesized laboratorially or possibly found on
      other planets, is considered in this paper. The three-component information
      energetic-structural irreducible processing in autonomous systems is the core of
      the proposed approach. The cybernetic organization of a general entity of life-
      the alivon--is postulated. The crucial properties of life and evolution are
      derived from the proposed approach. Information encoded in biological structures
      is also studied.

PMID- 25985761
TI  - Endoscopically visible steam pop during high-energy laser pulmonary vein
      ablation.
AB  - A 58-year-old woman with atrial fibrillation underwent laser balloon ablation at
      our centre. During 12 W ablation in the left superior pulmonary vein, a sudden
      steam pop was witnessed with displacement of the balloon catheter. Visualisation
      of the pulmonary vein antrum showed a red discolouration at the last ablation
      site. 

PMID- 25985760
TI  - Endovascular catheter ablation of ventricular tachycardia in a patient with a
      surgically repaired congenital left ventricular aneurysm.
AB  - We present a patient with a congenital left ventricular aneurysm who visited our
      outpatient clinic for a routine check-up and, during this visit, lost
      consciousness due to sustained ventricular tachycardia. In our patient,
      endocardial mapping revealed extensive conduction abnormalities, and successful
      ablation was accomplished at the endocardial surface. 

PMID- 25985762
TI  - Ultra-stretchable conductors based on buckled super-aligned carbon nanotube
      films.
AB  - Ultra-stretchable conductors are fabricated by coating super-aligned carbon
      nanotube (SACNT) films on pre-strained polydimethylsiloxane (PDMS) substrates and
      forming buckled SACNT structures on PDMS after release of the pre-strain. The
      parallel SACNT/PDMS conductors demonstrate excellent stability with normalized
      resistance changes of only 4.1% under an applied strain as high as 200%. The
      SACNT/PDMS conductors prepared with cross-stacked SACNT films show even lower
      resistance variation. The parallel SACNT/PDMS conductors exhibit high durability
      with a resistance increase of less than 5% after 10,000 cycles at 150% strain. In
      situ microscopic observations demonstrate that the buckled SACNT structures are
      straightened during the stretching process with reversible morphology evolution
      and thus the continuous SACNT conductive network can be protected from fracture.
      Due to the excellent electrical and mechanical properties of SACNT films and the
      formation of the buckled structure, SACNT/PDMS films exhibit high stretchability
      and durability, possessing great potential for use as ultra-stretchable
      conductors for wearable electronics, sensors, and energy storage devices.

PMID- 25985763
TI  - DNA damage and oxidative status in PFAPA syndrome.
AB  - OBJECTIVE: PFAPA syndrome is a clinical entity of unknown etiology which presents
      with periodic episodes of fever, aphthous stomatitis, tonsillitis or pharyngitis,
      and cervical adenitis. In this study we investigated DNA damage and the oxidative
      stress parameters in patients diagnosed with PFAPA, to elucidate the underlying
      pathophysiological mechanism of this syndrome. METHODS: Thirty-one patients
      diagnosed with PFAPA (Group 1), 22 patients diagnosed with normal tonsillitis or
      pharyngitis (Group 2), and 20 healthy volunteers (Group 3) were included in our
      study. Heparinized peripheral blood samples were drawn from all patients and
      volunteers. DNA damage was assessed by single cell alkaline electrophoresis assay
      in peripheral mononuclear leukocytes. Plasma levels of total antioxidant status
      (TAS) and total oxidative status (TOS) were determined by using a novel automated
      measurement method, and oxidative stress index (OSI) was calculated. RESULTS: DNA
      damage in the mononuclear leukocytes of Group 1 was significantly higher than
      that of Group 2 and Group 3. The oxidative stress parameters revealed that the
      TOS and OSI values of Group 1 were significantly higher than those of Group 2 and
      Group 3. TAS values of Group 1 were significantly lower than those of Group 2 and
      Group 3. Correlation analysis of Group 1 demonstrated a significant correlation
      between TOS, one of the oxidative stress parameters, and DNA damage. Correlations
      between DNA damage and C-reactive protein (CRP) and erythrocyte sedimentation
      rate (ESR) values were also significant. CONCLUSION: Our study indicated that
      both the inflammatory and the oxidative stress parameters were significantly
      increased in patients with PFAPA syndrome, accompanied by a significant positive
      correlation between DNA damage and oxidative stress.

PMID- 25985764
TI  - Aggressive Central Giant Cell Granuloma of the Mandible Treated With Conservative
      Surgical Enucleation and Interferon-alpha-2a: Complete Remission With Long-Term
      Follow-Up.
AB  - Central giant cell granuloma (CGCG) is a benign tumor of the jaws. Aggressive
      lesions present a strong tendency toward recurrence after surgical enucleation;
      thus, en bloc resection and microvascular bone free flap transfer are usually
      performed. However, in young patients, aggressive surgical treatment is a not
      always suitable solution. This report describes the case of a young female
      patient who developed an aggressive recurrence of CGCG after its diagnosis and
      enucleation from the mandible. Surgical enucleation with subcutaneous injection
      of interferon-alpha-2a was performed. The patient was evaluated every 6 weeks,
      and after 6 months radiographic evidence of complete bone regeneration was
      obtained. No sign of recurrence was seen after 8 years of follow-up. A review of
      the literature proved that interferon treatment is an effective strategy to avoid
      extensive surgery in patients with aggressive CGCG. 

PMID- 25985765
TI  - New strategies to address the pharmacodynamics and pharmacokinetics of tumor
      necrosis factor (TNF) inhibitors: A systematic analysis.
AB  - AIM: To assess the putative link between antibody formation to adalimumab,
      infliximab and etanercept, circulating drug levels and clinical outcomes.
      METHODS: A literature search was conducted using Pubmed from inception to 5th
      March 2013 of original research articles relating to adalimumab, etanercept and
      infliximab that investigated the immunogenicity of each drug. Data were extracted
      to document the disease, anti-TNF-alpha agent, regimen, study design, use of
      concomitant immunosuppressive therapy, the relationship between drug
      administration and antibody assessment, the type of immunoassay and cut-off,
      plasma drug concentration, frequency of antibody and clinical assessments,
      antibody positivity rate and relationship between antibody positivity and
      clinical outcome. Studies were stratified by drug, disease area and whether or
      not concomitant immunosuppressive therapy had been given. All data were tabulated
      by publication and analyzed descriptively. RESULTS: A total of 57 original
      research articles were included in the analysis (infliximab n=34; adalimumab
      n=18; etanercept n=5). There was considerable heterogeneity in study design,
      methodology for anti-drug antibody detection and drug bioavailability evaluation.
      Consequently, it was difficult to compare the immunogenic potential of
      infliximab, adalimumab and etanercept, particularly because different assays with
      variable sensitivity and specificity were used. The timing of occurrence and the
      persistence of anti-drug antibodies appeared to be influenced by administration
      schedules and concomitant immunosuppressive therapy. Monitoring of circulating
      drug levels and anti-drug antibodies appears to be an emerging and cost-effective
      strategy for the management of the individual patient. CONCLUSIONS: Monitoring
      drug and anti-drug antibody levels appears to be a putative strategy for optimal
      and cost-effective intervention. However studies of consistent and homogeneous
      design, methodology and duration are warranted to assess the true incidence and
      consequences of immunogenicity.

PMID- 25985766
TI  - An ethnobotanical perspective on traditional fermented plant foods and beverages
      in Eastern Europe.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fermented food and beverages represent an
      important part of the worldwide foodscape, medicinal food domain and domestic
      strategies of health care, yet relevant traditional knowledge in Europe is poorly
      documented. METHODS: Review of primary ethnographic literature, archival sources
      and a few ad-hoc ethnobotanical field studies in seven selected Eastern European
      countries (Albania, Belarus, Bulgaria, Estonia, Hungary, Kosovo, and Poland) were
      conducted. RESULTS: Current or recently abandoned uses of 116 botanical taxa,
      belonging to 37 families in fermented food or medicinal food products were
      recorded. These findings demonstrate a rich bio-cultural diversity of use, and
      also a clear prevalence of the use of fruits of the tannin- and phenolic-rich
      Rosaceae species in alcoholic, lactic- and acetic acid fermented preparations. In
      the considered countries, fermentation still plays (or has played until recent
      years) a crucial role in folk cuisines and this heritage requires urgent and in
      depth evaluation. DISCUSSION: Future studies should be aimed at further
      documenting and also bio-evaluating the ingredients and processes involved in the
      preparation of homemade fermented products, as this can be used to support local,
      community-based development efforts to foster food security, food sovereignty,
      and small-scale local food-based economies.

PMID- 25985767
TI  - Urine and plasma metabonomics coupled with UHPLC-QTOF/MS and multivariate data
      analysis on potential biomarkers in anemia and hematinic effects of herb pair Gui
      Hong.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The compatibility of Angelicae Sinensis Radix
      (Danggui) and Carthami Flos (Honghua), a famous herb pair Gui-Hong, can produce
      synergistic and complementary hematinic effects. Our previous studies have
      indicated that Gui-Hong has therapeutic potential treatment in hemolytic and
      aplastic anemia (HAA). The present study aimed to investigate the hematinic
      effects of Danggui, Honghua and Gui-Hong on HAA rats induced by acetyl
      phenylhydrazine (APH) and cyclophosphamide (CP) and to explore the underlying
      hematinic regulation mechanisms. MATERIALS AND METHODS: Rats were divided into 5
      groups, and drugs were administered by oral gavage one time each day for
      continuous 7 days from the experiment began. Urine and plasma were analyzed by
      ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight
      mass spectrometry (UHPLC-QTOF/MS). Partial least-squares discriminate analysis
      (PLS-DA) models were built to evaluate the therapeutic effects of Danggui,
      Honghua and Gui-Hong. Pearson correlation matrix analysis method was used to
      discover the correlations between potential biomarkers and biochemical indicators
      of HAA rats. RESULTS: Seven potential biomarkers contribute to the separation of
      model group and control group were tentatively identified. The levels of l
      kynurenine, phenylalanine, nicotinic acid and sphingosine increased significantly
      (P<0.05) in HAA rats, while the levels of l-isoleucine, l-tyrosine and serotonin
      decreased significantly (P<0.05) in comparison with control rats. Those
      endogenous metabolites were chiefly involved in phenylalanine, tyrosine and
      tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, tryptophan
      metabolism and tyrosine metabolism. The metabolic deviations could be regulated
      closer to normal level after Danggui, Honghua and Gui-Hong intervention. In term
      of hematinic effects, Gui-Hong was the most effective as shown by the relative
      distance in PLS-DA score plots and relative intensity of potential biomarkers.
      The result reflected the synergic action between Danggui and Honghua. The above
      results were found to be reasonable in explaining the hematinic effects mechanism
      of Gui-Hong. CONCLUSIONS: The results of routine blood, urinary metabolic pattern
      and plasma metabolic pattern show the Danggui, Honghua and Gui-Hong groups are
      moving toward the control group and the HAA was being prevented and alleviated.
      The effect of Gui-Hong group is more remarkable than Danggui and Honghua groups.
      Some potential biomarkers like l-kynurenine, phenylalanine, l-isoleucine, l
      tyrosine, serotonin, nicotinic acid and sphingosine have been found and
      identified. The work shows that the metabonomics method is a promising tool in
      the efficacy and mechanism research of traditional Chinese medicines.

PMID- 25985768
TI  - Lythrum salicaria L.-Underestimated medicinal plant from European traditional
      medicine. A review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Purple loosestrife-Lythrum salicaria L. is a
      herbaceous perennial plant belonging to the Lythraceae family. It has been used
      for centuries in European traditional medicine. Despite Lythri herba being a
      pharmacopoeial plant material (Ph. Eur.), L. salicaria popularity as a medicinal
      plant has recently declined. The aim of the paper is to recall a traditional and
      historical use of L. salicaria and juxtapose it with comprehensive view on the
      current knowledge about its chemical composition and documented biological
      activities in order to bring back the interest into this valuable plant and
      indicate reasonable directions of future research and possible applications.
      MATERIALS AND METHODS: Systematic survey of historical and ethnopharmacological
      literature was carried out using sources of European and American libraries.
      Pharmacological and phytochemical literature research was performed using Scopus,
      PubMed, Web of Science and Reaxys databases. RESULTS: The review of historical
      sources from ancient times till 20th century revealed an outstanding position of
      L. salicaria in traditional medicine. The main applications indicated were
      gastrointestinal tract ailments (mainly dysentery and diarrhea) as well as
      different skin and mucosa affections. The current phytochemical studies have
      shown that polyphenols (C-glucosidic ellagitannins and C-glucosidic flavonoids)
      as well as heteropolysaccharides are dominating constituents, which probably
      determine the observed pharmacological effects. The extracts and some isolated
      compounds were shown to possess antidiarrheal, antimicrobial, anti-oxidant, anti
      inflammatory and anti-diabetic activities. CONCLUSIONS: The intrinsic literature
      overview conclusively demonstrates that L. salicaria L. used to be considered as
      an exceptionally effective remedy in European traditional medicine. Despite its
      unquestionable important position from unknown reasons its popularity has been
      weakened during the past few decades. Unfortunately the contemporary
      pharmacological research is still insufficient to support its thoroughly
      described traditional uses. The necessity of complex studies regarding modes of
      action, which would directly refer to L. salicaria main traditional applications
      gastrointestinal tract ailments, is strongly underlined.

PMID- 25985769
TI  - T-wave/QRS complex amplitude correlations with myocardial edema in patients with
      takotsubo syndrome.

PMID- 25985759
TI  - An integrative view on sex differences in brain tumors.
AB  - Sex differences in human health and disease can range from undetectable to
      profound. Differences in brain tumor rates and outcome are evident in males and
      females throughout the world and regardless of age. These observations indicate
      that fundamental aspects of sex determination can impact the biology of brain
      tumors. It is likely that optimal personalized approaches to the treatment of
      male and female brain tumor patients will require recognizing and understanding
      the ways in which the biology of their tumors can differ. It is our view that sex
      specific approaches to brain tumor screening and care will be enhanced by
      rigorously documenting differences in brain tumor rates and outcomes in males and
      females, and understanding the developmental and evolutionary origins of sex
      differences. Here we offer such an integrative perspective on brain tumors. It is
      our intent to encourage the consideration of sex differences in clinical and
      basic scientific investigations. 

PMID- 25985773
TI  - Salt tolerance is evolutionarily labile in a diverse set of angiosperm families.
AB  - BACKGROUND: Salt tolerance in plants is rare, yet it is found across a diverse
      set of taxonomic groups. This suggests that, although salt tolerance often
      involves a set of complex traits, it has evolved many times independently in
      different angiosperm lineages. However, the pattern of evolution of salt
      tolerance can vary dramatically between families. A recent phylogenetic study of
      the Chenopodiaceae (goosefoot family) concluded that salt tolerance has a
      conserved evolutionary pattern, being gained early in the evolution of the
      lineage then retained by most species in the family. Conversely, a phylogenetic
      study of the Poaceae (grass family) suggested over 70 independent gains of salt
      tolerance, most giving rise to only one or a few salt tolerant species. Here, we
      use a phylogenetic approach to explore the macroevolutionary patterns of salt
      tolerance in a sample of angiosperm families, in order to ask whether either of
      these two patterns - deep and conserved or shallow and labile - represents a
      common mode of salt tolerance evolution. We analyze the distribution of halophyte
      species across the angiosperms and identify families with more or less halophytes
      than expected under a random model. Then, we explore the phylogenetic
      distribution of halophytes in 22 families using phylogenetic comparative methods.
      RESULTS: We find that salt tolerance species have been reported from over one
      third of angiosperm families, but that salt tolerant species are not distributed
      evenly across angiosperm families. We find that salt tolerance has been gained
      hundreds of times over the history of the angiosperms. In a few families, we find
      deep and conserved gains of salt tolerance, but in the majority of families
      analyzed, we find that the pattern of salt tolerant species is best explained by
      multiple independent gains that occur near the tips of the phylogeny and often
      give rise to only one or a few halophytes. CONCLUSIONS: Our results suggest that
      the pattern of many independent gains of salt tolerance near the tips of the
      phylogeny is found in many angiosperm families. This suggests that the pattern
      reported in the grasses of high evolutionary lability may be a common feature of
      salt tolerance evolution in angiosperms.

PMID- 25985771
TI  - Predicting Effectiveness of Imatinib Mesylate in Tumors Expressing Platelet
      Derived Growth Factors (PDGF-AA, PDGF-BB), Stem Cell Factor Ligands and Their
      Respective Receptors (PDGFR-alpha, PDGFR-beta, and c-kit).
AB  - INTRODUCTION: This research aims to optimize and predict the effectiveness of
      imatinib mesylate (imatinib) in tumors expressing platelet-derived growth factors
      (PDGF-AA, BB), kit/stem cell factor (SCF) ligands and their respective receptors
      (PDGFR-alpha, PDGFR-beta, and c-kit). MATERIAL AND METHODS: Samples of normal
      primary human T cells were incubated with graded concentrations of 1-5 MUM
      imatinib. The energy yield by imatinib doses in those samples was identified in H
      thymidine proliferation assay as described before in earlier studies. Tumor
      models of human pancreatic adenocarcinoma L3.6pl (PDGFAA/PDGFR-alpha-positive and
      KIT-negative), human male gonad Leydig tumor cells MA10 (PDGF-AA/PDGFR-alpha-
      positive and KIT-positive), human small-cell lung cancer [H209 (KIT-positive),
      NCI-H526 (PDGFR beta-positive and KIT-positive), and NCI-H82 (PDGFR beta-positive
      and KIT-negative)], and human neuroblastoma SMS-KCNR (PDGF-BB/PDGFR-beta-positive
      and KIT-positive) in athymic nude mice were used. The antitumor activity of
      different doses of imatinib in different regimens in those xenografts was
      predicted as described before in earlier studies. RESULTS: The energy yield by
      drug doses was perfectly logarithmic correlated (r = 1) with the drug dose. An
      efficient dose-energy model with perfect fit (R = 1) estimating the energy yield
      by imatinib doses has been established to administer the personalized dose.
      Predictions for the antitumor activity of imatinib in those xenografts using the
      dose-energy model and the histologic grade of the control animals were 100 %
      identical to those actually induced. CONCLUSION: The effect of imatinib is
      transient and reversible, reduces tyrosine phosphorylation of tumor-derived PDGFR
      alpha, PDGFR-beta, and c-kit without affecting their levels of expression. A
      resumption of tumor growth nearly identical to the growth prior to therapy should
      be expected whenever the treatment is stopped. Tumors of PDGF-AA/PDGFR-alpha
      exhibit significant resistance to imatinib which requires administering imatinib
      three times a day, whereas resistance of tumors of PDGF-BB/PDGFR-beta or KIT
      positive is relatively lower which requires administering imatinib two times a
      day only to produce an actual inhibition 100 % identical to that predicted for
      tumor growth.

PMID- 25985776
TI  - [Lee Jungsook, a Korean independence activist and a nurse during the Japanese
      colonial period].
AB  - This article examines the life of Lee Jungsook, a Korean nurse, as a independence
      activist during the Japanese colonial period. Lee Jungsook(1896-1950) was born in
      Bukchung in Hamnam province. She studied at Chungshin girl's high school and
      worked at Severance hospital. The characteristics and culture of her educational
      background and work place were very important factors which influenced greatly
      the life of Lee Jungsook. She learned independent spirit and nationalism from
      Chungshin girls' high school and worked as nurse at the Severance hospital which
      were full of intense aspiration for Korea's independence. Many of doctors,
      professors and medical students were participated in the 3.1 Independence
      Movement. Lee Jungsook was a founding member of Hyulsungdan who tried to help the
      independence activists in prison and their families and worked as a main member
      of Korean Women's Association for Korean Independece and Kyungsung branch of the
      Korean Red Cross. She was sent to jail by the Japanese government for her
      independence activism. After being released after serving two years confinement,
      she worked for the Union for Women's Liberation as a founding member. Lee
      Joungsook was a great independence activist who had a nursing care spirit as a
      nurse. 

PMID- 25985770
TI  - Gut-Associated Bacteria of Dendroctonus valens and their Involvement in Verbenone
      Production.
AB  - Bark beetles are the most important mortality agent in coniferous forests, and
      pheromones play important roles in their management. Dendroctonus valens LeConte
      was introduced from North America to China and has killed millions of healthy
      pines there. Trapping with semiochemicals and pheromones was deployed in D.
      valens management in the last decade, but little is known about the ability of
      gut bacteria to produce the pheromone. In this study, we analyzed the volatiles
      in D. valens guts and frass after antibiotic treatment versus control. Then, we
      isolated and identified the bacteria in D. valens guts and frass, examined
      verbenone (a multifunctional pheromone of D. valens) production by 16 gut
      bacterial isolates from the precursor cis-verbenol at three concentrations, and
      further compared the cytotoxicities between the cis-verbenol and verbenone to the
      bacterial isolates. cis-Verbenol was not detected in the frass in the control
      group, but it was in the antibiotic treatment. The amount of verbenone was
      significantly suppressed in D. valens guts after antibiotic treatment versus
      control. Thirteen out of 16 gut bacterial isolates were capable of cis-verbenol
      to verbenone conversion, and cis-verbenol had stronger cytotoxicities than
      verbenone to all tested gut bacterial isolates. The bacterial species capable of
      verbenone production largely exists in D. valens guts and frass, suggesting that
      gut-associated bacteria may help the bark beetle produce the pheromone verbenone
      in guts and frass. The bacteria may benefit from the conversion due to the
      reduced cytotoxicity from the precursor to the beetle pheromone. 

PMID- 25985772
TI  - Dietary behaviour and parental socioeconomic position among adolescents: the
      German Health Interview and Examination Survey for Children and Adolescents 2003
      2006 (KiGGS).
AB  - BACKGROUND: The positive association between parental socioeconomic position
      (PSEP) and health among adolescents may be partly explained by dietary behaviour.
      We investigated the associations between fruit intake, vegetable intake, energy
      dense food intake, the Healthy Nutrition Score for Kids and Youth (HuSKY) and
      parental education in a nationwide, cluster-randomized sample of adolescents in
      Germany. METHODS: The German Health Interview and Examination Survey for Children
      and Adolescents 2003-2006 (KiGGS) included 17,641 individuals aged 0-17 years and
      their parents. Complete information on relevant variables was available for 6359
      individuals in the 11-17 age group. The associations between nutrition indicators
      and parental education were analysed separately for boys and girls, using
      multivariate logistic regression analysis. Odds ratios (ORs) adjusted for age,
      region, income, occupation, physical activity and weight status related
      variables, were calculated for the associations between parental education and
      nutrition indicators. RESULTS: After full adjustment, higher parental education
      level was associated with lower energy-dense food intake - with an OR of 1.3 (95
      % CI 1.0-1.7) for boys with secondary educated parents and 1.8 (1.4-2.3) for boys
      with tertiary educated parents compared to boys with primary educated parents;
      the corresponding ORs for girls were 1.2 (0.9-1.5) and 1.6 (1.2-2.2). Higher
      parental education was associated with higher fruit intake - with an OR of 1.3
      (1.0-1.7) for boys with secondary educated parents and 2.0 (1.5-2.7) for boys
      with tertiary educated parents compared to boys with primary educated parents;
      the corresponding ORs for girls were 1.0 (0.8-1.4) and 1.5 (1.0-2.1). Among boys
      and girls with tertiary educated parents compared to those with primary educated
      parents an OR of 1.3 (CI boys: 1.0-1.7, CI girls: 1.0-1.6) was observed for high
      vegetable intake. Among boys with tertiary educated parents compared to boys with
      primary educated parents an OR of 1.6 (1.2-2.2) was observed for a high HuSKY;
      the corresponding OR for girls was 1.5 (1.1-1.9). CONCLUSIONS: A high PSEP is
      associated with consumption of less energy-dense food, more fruits and vegetables
      and more favourable overall dietary behaviour. Preferably school-based
      interventions are needed to promote healthy dietary behaviour among German
      adolescents and a special effort is needed to reach adolescents from low-PSEP
      families.

PMID- 25985777
TI  - U.S. military administration's malaria control activities (1945-1948).
AB  - To prevent and control infectious diseases was one of the major concerns of U.S.
      military government when they stationed in Korea in 1945. It was because the
      spread of various infectious diseases can cause social unrest and they can also
      affect the U.S. military. Malaria was one of the most important infectious
      diseases to which the U.S. military had been paying special attention. The U.S.
      military received a severe damage during the Pacific war with Japan due to
      malaria. It was said that more soldiers were lost by malaria than by battle
      itself. The bitter experience they had during the war made them accumulate more
      systematic and practical knowledge against malaria. As a result, by the end of
      the war, the U.S. military could run more than hundreds of units specialized in
      controlling malaria. Thanks to such a preparation, they could immediately begin
      their anti-malaria activities in Korea soon after the World War II. Although the
      vivax malaria, which is the dominant type in Korea, is not as much a fatal type
      as that in the Pacific areas, it was damaging enough to the infected. The 207th
      Malaria Survey Detachment carried out collecting and identifying the kinds of
      mosquitos in Korea. In addition, they also surveyed the prevalence of malaria
      among school children in Seoul. In terms of controlling malaria, DDT played a
      decisive role. Vector control is the most effective and ideal measurements
      against malaria. Before the development of DDT, it was practically impossible to
      eradicate mosquitos which arise from extremely broad areas. However, DDT could
      not be used as it had been expected in the rural area, because spraying DDT in
      the rice paddies which is the breeding place of mosquitos kills rice. Despite
      such a limitation in anti-malaria activities of the US military government, it
      should be noted that a significant turn in controlling malaria was possible
      thanks to the development of DDT.

PMID- 25985775
TI  - A call centre and extended checklist for pre-screening elective surgical patients
      - a pilot study.
AB  - BACKGROUND: Novel approaches to preoperative assessment and management before
      elective surgery are warranted to ensure that a sustainable high quality service
      is provided. The benefits of a call centre incorporating an extended preoperative
      electronic checklist and phone follow-up as an alternative to a clinic attendance
      were examined. METHODS: This was a pilot study of a new method of patient
      assessment in patients scheduled for elective non-cardiac surgery and who
      attended a conventional preoperative clinic. A call centre assessment, using a
      Computer-assisted Health Assessment by Telephone (CHAT), paper review by an
      anaesthetist, and a follow-up phone call if the anaesthetist wished more
      information, preceded the conventional preoperative clinic. Summaries from the
      call centre and clinic assessments were independently produced. The times spent
      by call centre staff were recorded. The 'procedural anaesthetist' (who provided
      anaesthesia for each patient's actual surgery/procedure) documented an opinion on
      whether the call centre assessment alone would have been sufficient to bypass the
      preoperative clinic if the patient were hypothetically undergoing laparoscopic
      cholecystectomy. This opinion was also sought from a panel of four senior
      anaesthetists, based on patient summaries from both the call centre and
      preoperative clinic, but expanded to three hypothetical operations of different
      complexity - cataract removal, laparoscopic cholecystectomy, and total hip
      replacement. RESULTS: Call centre assessment followed by clinic attendance was
      studied in 193 patients. The mean time for CHAT was 19.8 (SD 7.5) minutes and,
      after review of CHAT summaries, anaesthetists telephoned 45.6% of cases for
      follow-up information. The mean time spent by anaesthetists on summary review and
      phone calls was 3.8 (SD 3.9) minutes. Procedural anaesthetists considered 89% of
      the patients under their care suitable to have bypassed the preoperative clinic
      if they were to have undergone cholecystectomy. The panel of senior anaesthetists
      judged 95-97% of patients suitable to have bypassed preoperative clinic for
      cataract surgery, 81-85% for cholecystectomy and 79-82% for hip replacement.
      CONCLUSIONS: A call centre to pre-screen elective surgical patients might
      substantially reduce patient numbers attending preoperative anaesthetic
      assessment clinics. Further studies to assess the quality of such an approach are
      indicated. TRIAL REGISTRATION: ANZCTR ACTRN12614000199617.

PMID- 25985774
TI  - Patterns and determinants of care seeking for obstetric complications in rural
      northwest Bangladesh: analysis from a prospective cohort study.
AB  - BACKGROUND: In communities with low rates of institutional delivery, little data
      exist on care-seeking behavior for potentially life-threatening obstetric
      complications. In this analysis, we sought to describe care-seeking patterns for
      self-reported complications and near misses in rural Bangladesh and to identify
      factors associated with care seeking for these conditions. METHODS: Utilizing
      data from a community-randomized controlled trial enrolling 42,214 pregnant women
      between 2007 and 2011, we used multivariable multinomial logistic regression to
      explore the association of demographic and socioeconomic factors, perceived need,
      and service availability with care seeking for obstetric complications or near
      misses. We also used multivariable multinomial logistic regression to analyze the
      factors associated with care seeking by type of obstetric complication
      (eclampsia, sepsis, hemorrhage, and obstructed labor). RESULTS: Out of 9,576
      women with data on care seeking for obstetric complications, 77% sought any care,
      with 29% (n = 2,150) visiting at least one formal provider and 70% (n = 5,149)
      visiting informal providers only. The proportion of women seeking at least one
      formal provider was highest among women reporting eclampsia (57%), followed by
      hemorrhage (28%), obstructed labor (22%), and sepsis (17%) (p < 0.001). In
      multivariable analyses, socioeconomic factors such as living in a household from
      the highest wealth quartile (Relative Risk Ratio of 1.49; 95% CI of [1.33-1.73]),
      women's literacy (RRR of 1.21; 95% CI of [1.05-1.42]), and women's employment
      (RRR of 1.10; 95% CI of [1.01-1.18]) were significantly associated with care
      seeking from formal providers. Service factors including living less than 10
      kilometers from a health facility (RRR of 1.16; 95% CI of [1.05-1.28]) and
      facility availability of comprehensive obstetric services (RRR of 1.25; 95% CI of
      1.04-1.36) were also significantly associated with seeking care from formal
      providers. CONCLUSIONS: While the majority of women reporting obstetric
      complications sought care, less than a third visited health facilities.
      Improvements in socioeconomic factors such as maternal literacy, coupled with
      improved geographic access and service availability, may increase care seeking
      from formal facilities. Enhancing community awareness on symptoms of hemorrhage,
      sepsis, and obstructed labor and their consequences may promote care seeking for
      obstetric complications in rural Bangladesh. TRIAL REGISTRATION:  TRIAL
      REGISTRATION NUMBER: NCT00860470 .

PMID- 25985780
TI  - [A study on the awareness of Chinese medicine by medical missionaries: focused on
      the China Medical Missionary Journal (1887-1932)].
AB  - Protestant medical missionaries, who started entering China during the beginning
      of the 19th century, set the goal as propagating Western medicine to the Chinese
      while spreading the Christian gospel. Back in those days, China formed deep
      relations with their own ideology and culture and depended on Chinese medicine
      that caused major influence on their lives instead of just treatment behaviors.
      Accordingly, it is natural to see information about Chinese medicine in documents
      that were left behind. Yet, there are not many studies which dealt with the
      awareness of Chinese medicine by medical missionaries, and most were focused on
      the criticism imposed by medical missionaries regarding Chinese medicine. Thus,
      there are also claims amongst recent studies which impose how the medical
      missionaries moved from overlooking and criticizing Chinese medicine to gaining a
      "sympathetic viewpoint" to a certain degree. Still, when the documents left
      behind by medical missionaries is observed, there are many aspects which support
      how the awareness of Chinese medicine in medical missionaries has not changed
      significantly. In addition, medical missionaries actively used medicine like
      traditional Chinese drugs if the treatment effect was well known. Yet, they
      barely gave any interest to the five elements, which are the basics of
      traditional Chinese drugs prescription. In other words, medical missionaries only
      selected elements of Chinese medicine that were helpful to them just like how the
      Chinese were choosing what they needed from Western knowledge. The need to
      understand Chinese medicine was growing according to the flow of times. For
      instance, some medical missionaries admitted the treatment effect of acupuncture
      in contrast to claiming it as non-scientific in the past. Such changes were also
      related to how focused medical missionaries were on medical activities. The first
      medical missionaries emphasized the non-scientific aspect of Chinese medicine to
      verify the legitimacy of medical mission. Then, medical missionaries gradually
      exerted more efforts on medical treatment than direct mission activities so the
      need of Chinese medicine became greater. This was because Chinese relied on
      Chinese medicine the most and even used Chinese medicine terms that they knew to
      explain their conditions while getting treatment from doctors who learned Western
      medicine. Additionally, medicine missionaries witnessed patients getting better
      after receiving treatment so they could not completely overlook Chinese medicine.
      However, medical missionaries strongly believed in the superiority of Western
      medicine and considered that China certainly needed Western medicine from a
      scientific perspective. Chinese doctors who were close to medical missionaries
      and learned about Western medicine believed in Western medicine and thought that
      Chinese medicine only held historical value besides some fields like Chinese
      traditional drugs. 

PMID- 25985779
TI  - [Obstetric medical book and women's childbirth in Qing dynasty: the case of the
      treatise on easy childbirth].
AB  - Ye Feng composed what was to become one of the most famous and widely-circulating
      medical works of the late imperial period, the Treatise on Easy Childbirth. Ye
      Feng proposed the idea of natural childbirth, When the correct moment for birth
      had arrived, the child would leave its mother's body as easily as "a ripe melon
      drops from the stem". He argued attempts to facilitate birth were therefore not
      only unnecessary, and female midwives artificial intervention was not required.
      However, this view is to overlook the pangs of childbirth, and women bear
      responsibility for the failure of delivery. So his views reflect the gender order
      in male-dominated. Also he constructed the negative image of the midwife and
      belittle her childbirth techniques. As a result, midwife are excluded from the
      childbirth field, male doctors grasp guardianship rights of the female body. Ye
      Feng declared that the key to safe and successful delivery could be summed up in
      just a few words: "sleep, endure the pain, delay approaching the birthing tub".
      This view must be consistent with the Confucian norms, women to export to equip
      the 'patience' and 'self-control'. These norms were exposed desire men want to
      monitor and control the female body, effect on consolidation of patriarchal
      family order. In sum, the discourse of "a ripe melon drops from the stem"and
      "sleep, endure the pain, delay approaching the birthing tub" comprised an
      important intellectual resource that male doctors drew on to legitimate
      themselves as superior overseers of women's gestational bodies. 

PMID- 25985782
TI  - "If I only touch her cloak": the Sisters of Charity of St. Joseph in New Orleans
      hospital, 1834-1860.
AB  - This study is about the Sisters of Charity of St. Joseph in New Orleans' Charity
      Hospital during the years between 1834 and 1860. The Sisters of Charity of St.
      Joseph was founded in 1809 by Saint Elizabeth Ann Bailey Seton (first native-born
      North American canonized in 1975) in Emmitsburg, Maryland. Seton's Sisters of
      Charity was the first community for religious women to be established in the
      United States and was later incorporated with the French Daughters of Charity of
      St. Vincent de Paul in 1850. A call to work in New Orleans' Charity Hospital in
      the 1830s meant a significant achievement for the Sisters of Charity, since it
      was the second oldest continuously operating public hospitals in the United
      States until 2005, bearing the same name over the decades. In 1834, Sister Regina
      Smith and other sisters were officially called to Charity Hospital, in order to
      supersede the existing "nurses, attendants, and servants," and take a complete
      charge of the internal management of Charity Hospital. The existing scholarship
      on the history of hospitals and Catholic nursing has not integrated the concrete
      stories of the Sisters of Charity into the broader histories of institutionalized
      medicine, gender, and religion. Along with a variety of primary sources, this
      study primarily relies on the Charity Hospital History Folder stored at the
      Daughters of Charity West Center Province Archives. Located in the "Queen city of
      the South," Charity Hospital was the center of the southern medical profession
      and the world's fair of people and diseases. Charity Hospital provided the
      sisters with a unique situation that religion and medicine became intertwined.
      The Sisters, as nurses, constructed a new atmosphere of caring for patients and
      even their families inside and outside the hospital, and built their own separate
      space within the hospital walls. As hospital managers, the Sisters of Charity
      were put in complete charge of the hospital, which was never seen in other
      hospitals. By wearing a distinctive religious garment, they eschewed female
      dependence and sexuality. As medical and religious attendants at the sick wards,
      the sisters played a vital role in preparing the patients for a "good death" as
      well as spiritual wellness. By waging their own war on the Protestant influences,
      the sisters did their best to build their own sacred place in caring for sick
      bodies and saving souls. Through the research on the Sisters of Charity at
      Charity Hospital, this study ultimately sheds light on the ways in which a
      nineteenth-century southern hospital functioned as a unique environment for the
      recovery of wellness of the body and soul, shaped and envisioned by the Catholic
      sister-nurses' gender and religious identities. 

PMID- 25985778
TI  - [The disease and treatment of the frontline soldiers in Han dynasty].
AB  - This paper purports to identify and analyze the medical information of the
      frontline soldiers in the Northwest borderland provinces of Han Dynasty,
      especially Juyan and Dunhuang region, through an heuristic reading of the Juyan
      Bamboo Slips and the Dunhuang Bamboo Slips of the Han Dynasty. My findings are as
      follows. The most frequent disease found in the bamboo slips was the external
      injury. The injury of the frontline soldiers mainly occurred from the quarrels
      among armed soldiers using weapons. The bamboo slips also demonstrate that the
      quarrels usually arose due to the fierce tension caused by the frontier line
      service such as heavy guard activity and labour duty. Undernourishment and
      chronic stress the soldiers suffered might be another reasons. The second most
      common disease harassing the soldiers was exogenous febrile disease. In most
      cases reviewed in this paper, the exogenous febrile disease was usually
      concurrent with complex symptoms such as chills, fever, headache, etc. The bamboo
      slips show that the exogenous febrile disease was related to the harsh climate of
      the Northwest provinces, featuring extremely dry weather and the large magnitude
      of diurnal temperature fluctuations. In addition, the annual temperature range in
      the Northwest province was huge, fluctuating between very cold and dry winter and
      very hot and dry summer. The third most common disease this study identified was
      the disorder of the digestive system and respiratory system. However, these two
      types of disease were virtually indistinguishable in the bamboo slips, because
      the ancient Chinese chroniclers did not distinguish them, usually dubbing both
      diseases simply 'abdominal pain.' It should be mentioned that a few slips mention
      contagious disease such as dysentery and dermatolosis, and sudden death, as well.
      Overall, the bamboo slips demonstrate extremely poor status of the soldiers'
      heath condition and poor medical environment surrounding the soldiers stationing
      in the Northwest borderland military camps. The records also show that
      acupuncture, applying a plaster, drugs were the most common medical treatment.
      Drugs among them was the most frequently used. Whereas Acupuncture, applying a
      plaster were very rarely used. Medication has been used in three ways: powdered
      medicine, medicinal decoction and pill. Medicinal decoction was the most commonly
      used way. 

PMID- 25985781
TI  - [A development of Byzantine Christian charities during the 4(th)-7(th) centuries
      and the birth of the hospital].
AB  - This study aims to examine the beginning and the development of Christian
      Charities during the 4(th)-6(th) centuries which would eventually result in the
      birth of the hospital in modern sense in the first half of the 7(th) century. For
      this purpose, I looked carefully into various primary sources concerning the
      early Christian institutions for the poor and the sick. Above all, it's proper to
      note that the first xenodocheion where hospitality was combined with a systematic
      caring, is concerned with the Trinitarian debate of the 4(th) century. In 356,
      Eustathios, one of the leaders of homoiousios group, established xenodocheion to
      care for the sick and the lepers in Sebaste of Armenia, whereas his opponent
      Aetios, doctor and leader of the heteroousios party, was reckoned to have
      combined the medical treatment with his clerical activities. Then, Basil of
      Caesarea, disciple of Eustathios of Sebaste, also founded in 372 a magnificent
      benevolent complex named 'Basileias' after its founder. I scrupulously analysed
      several contemporary materials mentioning the charitable institution of Caesarea
      which was called alternatively katagogia, ptochotropheion, xenodocheion. John
      Chrysostome also founded several nosokomeia in Constantinople at the end of the
      4(th) century and the beginning of the 5(th) century. Apparently, the
      contemporary sources mention that doctors existed for these Charities, but there
      is no sufficient proof that these 'Christian Hospitals,' Basileias or nosokomeia
      of Constantinople were hospitals in modern sense. Imperial constitutions began to
      mention ptochotropheion, xenodocheion and orphanotropheion since the second half
      of the 5(th) century and then some Justinian laws evoked nosokomium,
      brephotrophia, gerontocomia. These laws reveal that 'Christian Hospitals' were
      well clarified and deeply rooted in Byzantine society already in these periods.
      And then, new benevolent institutions emerged in the 6(th) century: nosokomeia
      for a specific class and lochokomeia for maternity. In addition, one of the
      important functions of Sampson Xenon was, according to Novel 59, to hold a
      funeral service for the people of Constantinople. Nevertheless, there is no
      sufficient literary material that could demonstrate the existence of a hospital
      in modern sense. The first hospital where outpatient service, hospitalization and
      surgery were confirmed was Sampson Xenon in the first half of the 7th century,
      figured in the tale of Stephanos of the The Miracles of St. Artemios. Why was the
      early Byzantine literary so reticent as to write the medical activities in the
      Christian Charities? It's because Christian innovation didn't rest on the medical
      treatment but caring for the poor and the sick, depending on the word of Mt.
      25.35-36. In this meaning, I'd like to say that the Early Byzantine history of
      Christian Charities or 'Christian Hospitals' consists of only a footnote of the
      verse. 

PMID- 25985785
TI  - Comparative Assessment of Guidewire and Microcatheter vs a Crossing Device-Based
      Strategy to Traverse Infrainguinal Peripheral Artery Chronic Total Occlusions.
AB  - PURPOSE: To compare success rates of a guidewire and microcatheter strategy vs
      the use of specialized crossing devices to traverse infrainguinal peripheral
      artery chronic total occlusions (CTOs). METHODS: For this analysis, data on 438
      consecutive infrainguinal CTO interventions in 438 patients (mean age 63.2 years;
      402 men) performed between August 2006 and May 2014 were extracted from the
      multicenter Excellence in Peripheral Artery Disease (XLPAD) database
      (ClinicalTrials.gov; identifier NCT01904851). Primary technical success
      constituted placement of a guidewire in the true lumen, past the distal CTO cap,
      with the initial crossing strategy. RESULTS: A wire-catheter strategy was used in
      295 (67.4%) and a specialized CTO crossing device in 143 (32.6%) patients
      (p<0.001). Primary crossing technical success was higher with CTO devices (72.1%
      vs 51.9%, p<0.001). The primary wire-catheter arm used significantly more
      secondary CTO devices (28.1% vs 17.5%) and/or provisional re-entry devices (26.7%
      vs 4.9%) compared with the primary CTO device arm (both p<0.001). Secondary
      crossing technical success (defined as crossing with an alternate strategy: 67.5%
      vs 71.4%, p=1.000), provisional crossing technical success (defined as use of a
      re-entry device: 84.2% vs 87.5%, p=0.768), and procedure success (93.6% vs 90.9%,
      p=0.332) were similar between the wire-catheter and CTO device strategies,
      respectively. No differences were observed in periprocedural complications or 30
      day adverse events; however, at 12 months, there was a significantly higher
      surgical revascularization rate in the primary wire-catheter arm (8.8% vs 2.8%,
      p=0.025). CONCLUSION: Infrainguinal peripheral artery CTO crossing is frequently
      attempted with a wire-catheter technique; however, an initial CTO crossing device
      approach is associated with higher primary technical success. Overall procedure
      success is similar with both strategies.

PMID- 25985786
TI  - Patient experience in a coordinated care model featuring diabetes self-management
      education integrated into the patient-centered medical home.
AB  - PURPOSE: The purpose of this study is to gain insight about patient experience of
      diabetes self-management education in a patient-centered medical home. METHODS:
      Six focus groups consisting of 37 people with diabetes, diverse in race and
      ethnicity, were conducted at 3 sites. Participants described their experience in
      the program and their challenges in diabetes self-management; they also suggested
      services to meet their diabetes care needs. RESULTS: The most common theme was
      ongoing concerns about care and support. There was much discussion about the
      value of the support provided by health navigators integrated in the diabetes
      health care team. Frequent concerns expressed by participants centered on
      personal challenges in engaging in healthy lifestyle behaviors. Ongoing
      programmatic support of self-management goals was widely valued. CONCLUSIONS:
      Individuals who received health care in a patient-centered medical home and could
      participate in diabetes self-management education with integrated support valued
      both activities. The qualitative results from this study suggest need for more
      formalized exploration of effective means to meet the ongoing support needs of
      people with diabetes.

PMID- 25985790
TI  - Organizing pneumonia appearing in B-cell chronic leukemia malignancy progression 
      a case report.
AB  - Patients with chronic lymphocytic leukemia or non-Hodgkin's lymphoma are at risk
      of infectious diseases of respiratory system because of immunodeficiency.
      Occurrence of organizing pneumonia in leukemic patients is most commonly
      correlated with bone marrow transplant or treatment with antimitotic agents.
      There have been only four reported cases of organizing pneumonia related
      solitarily to leukemia or lymphoma. We present a case of 65-year old gentlemen,
      diagnosed 8 months earlier with B-cell chronic lymphocytic leukemia with no
      previous hematologic treatment, who presented symptoms of persistent pneumonia
      with no significant reaction to antibiotics. Chest computed tomography scans
      showed well-localized consolidation with ground glass opacities and some air
      bronchogram, suggesting infectious disease. All results of microbiological
      examinations were negative. Due to radiological progression of parenchymal
      consolidation despite two intravenous courses of antibiotics open lung biopsy was
      performed. The histologic examination of lung specimen revealed structures
      typical for organizing pneumonia pattern. There was no evidence for leukemic
      involvement in lung tissue, as no sign for infectious factors from histological
      staining was observed. In the inferior mediastinal lymph node sample progression
      of chronic lymphatic leukemia to mixed cell lymphoma was diagnosed. Patient was
      commenced on prednisone 60 mg/daily with fast improvement. We believe that this
      is the first case of organizing pneumonia as a reaction to the conversion of B
      cell chronic lymphocytic leukemia progression to more malignant stage.

PMID- 25985789
TI  - Association between asthma control test, pulmonary function tests and non
      specific bronchial hyperresponsiveness in assessing the level of asthma control.
AB  - INTRODUCTION: Global Initiative for Asthma (GINA) reports emphasize the use of
      validated and simple tools in order to assess the level of asthma control, as the
      Asthma Control Test (ACT). However, an ACT does not include assessment of airway
      inflammation, which is better reflected when measuring nonspecific bronchial
      hyperresponsiveness (BHR). The authors aimed to find out if the level of asthma
      control quantified by an ACT correlates with BHR and pulmonary function tests.
      MATERIAL AND METHODS: 118 asthmatics participated in the study. All patients
      completed an ACT. The scores of the ACTs were compared with pulmonary function
      tests and BHR assessed with the methacholine challenge test and expressed as a
      provocative concentration of methacholine, inducing a 20% decline in the FEV1
      (PC20 M in mg/ml). RESULTS: Patients with controlled asthma amounted to 52 (44%)
      while those with uncontrolled asthma amounted to 66 (56%). In patients with
      controlled asthma (ACT score >= 20) the mean geometric value of PC20M was 2.72
      mg/ml (range from 0.25 to > 8.0), whereas 0.94 mg/ml (range from 0.28 to 8.0) (p
      = 0.02) was observed in patients with uncontrolled asthma (ACT score < 20).
      Almost 64% (21/33) of uncontrolled asthmatics achieved normal lung function (FEV1
      > 80% pred. value) while 19% (5/26) patients with controlled asthma presented an
      FEV1 < 80% predicted value. Asthma duration in years in controlled asthmatics was
      significantly shorter than in uncontrolled patients (6.2 +/- 8.9 vs. 12.0 +/-
      11.4, p = 0.005) CONCLUSION: In determining the most accurate level of asthma
      control it is reasonable to use an ACT in conjunction with BHR, which provides
      more accurate assessment of bronchial inflammation than ventilatory parameters
      alone.

PMID- 25985787
TI  - Association Between Kidney Dysfunction and Carotid Atherosclerosis in Community
      Based Older Adults in China.
AB  - We investigated the association between kidney dysfunction and carotid
      atherosclerosis in community-based older adults. This study consisted of 1257
      participants, aged 55 years and older and free of cardiovascular disease. Kidney
      dysfunction was classified as mild, moderate, and severe (estimated glomerular
      filtration rate, 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively). We found
      that the mean common carotid artery intima-media thickness (CCA-IMT)
      progressively increased with decrement in kidney function (P < .001). Even mild
      kidney dysfunction was significantly associated with CCA-IMT thickening (CCA-IMT
      >=1.0 mm; odds ratio [OR] 1.52; 95% confidence interval [CI] 1.16-1.99) compared
      to normal kidney function. A significantly increased presence of heterogeneous
      plaque was observed in relation to decreased kidney function (P for trend =
      .011), that is, even a mild kidney dysfunction was a potential independent risk
      factor for heterogeneous plaque (OR 1.43; 95% CI 1.04-1.98). Mild kidney
      dysfunction may be a predictor of early or accelerated carotid atherosclerosis in
      older adults. 

PMID- 25985788
TI  - Pulmonary presentation of Toxocara sp. infection in children.
AB  - INTRODUCTION: The aim of this study was to investigate the associations between
      radiological findings, blood eosinophilia, hyperimmunoglobulinemia E and G and
      Toxocara seropositivity in Polish children with newly diagnosed pulmonary
      infiltration. MATERIAL AND METHODS: We retrospectively analyzed the documentation
      of 119 patients, aged 1 to 18 years (mean age: 7.21 +/- 4.82), who were
      seropositive in Toxocara sp. antibodies. In all cases, peripheral blood
      eosinophils and leukocyte counts, serum total IgE, IgG levels and specific IgG
      antibodies against excretory and secretory Toxocara sp. antigens were measured at
      the first presentation. After the confirmation of seropositivity, all children
      had a routine radiological examination. RESULTS: In the documentation of 23
      children (mean age 3.58 +/- 2.63 years) we found abnormalities in the
      radiological examination of their lungs. Fifteen children who had abnormalities
      in radiological findings presented clinical respiratory complaints such as
      chronic cough, wheezing, asthma and haemoptysis. Eight children were
      asymptomatic. The analysis of peripheral eosinophils and leukocyte number, the
      level of IgE and specific anti-Toxocara IgG presented significantly higher values
      in children with radiological lesions than in children who had correct radiology.
      The concentrations of total IgG and gamma globulins were not significantly
      different. In 10 patients CT showed irregular round nodules with and without halo
      ranging from 1 to 13 mm. The number of nodules varied from a single lesion to
      multiple, disseminated ones. All nodules were located in peripheral areas of the
      lungs. None of them were found in the central areas. In 13 patients, CT images
      showed ground-glass opacities with ill-defined margins. None of the CT images
      presented lymphadenopathy and pleural effusion. CONCLUSION: The pulmonary lesions
      in small children with high eosinophilia and hyperimmunoglobulinemia E could be
      related to toxocariasis and for this reason they are eligible to undergo therapy
      with prolonged observation for several months, rather than start invasive
      malignancy investigations.

PMID- 25985791
TI  - Somatic Cell Therapy for Chronic Heart Failure: In Search of Mechanistic
      Insights.

PMID- 25985795
TI  - Involvement of Endoplasmic Reticulum Stress-Mediated C/EBP Homologous Protein
      Activation in Coxsackievirus B3-Induced Acute Viral Myocarditis.
AB  - BACKGROUND: This study tested the hypothesis whether endoplasmic reticulum (ER)
      stress/C/EBP homologous protein (CHOP) signaling is linked with coxsackievirus B3
      (CVB3)-induced acute viral myocarditis (AVMC) in vivo. METHODS AND RESULTS: AVMC
      was induced by intraperitoneal injection of 1000 tissue culture infectious dose
      (TCID50) of CVB3 virus in mice. In AVMC mouse hearts (n=11), ER stress and CHOP
      were significantly activated, and were linked to the induction of proapoptotic
      signaling including reduction of Bcl-2, activation of Bax and caspase 3, compared
      with the controls (n=10), whereas these could be markedly blocked by ER stress
      inhibitor tauroursodeoxycholic acid administration (n=11). Moreover, chemical
      inhibition of ER stress significantly attenuated cardiomyocytes apoptosis, and
      prevented cardiac troponin I elevation, ameliorated cardiac dysfunction assessed
      by both hemodynamic and echocardiographic analysis, reduced viral replication,
      and increased survival rate after CVB3 inoculation. We further discovered that
      genetic ablation of CHOP (n=10) suppressed cardiac Bcl-2/Bax ratio reduction and
      caspase 3 activation, and prevented cardiomyotes apoptosis in vivo, compared with
      wild-type receiving CVB3 inoculation (n=10). Strikingly, CHOP deficiency
      exhibited dramatic protective effects on cardiac damage, cardiac dysfunction,
      viral replication, and promoted survival in CVB3-caused AVMC. CONCLUSIONS: Our
      data imply the involvement of ER stress/CHOP signaling in CVB3-induced AVMC via
      proapoptotic pathways, and provide a novel strategy for AVMC treatment.

PMID- 25985797
TI  - Cross-talk between alpha7 nAChR-mediated cholinergic pathway and acylation
      stimulating protein signaling in 3T3-L1 adipocytes: role of NFkappaB and STAT3.
AB  - Inflammation is a key feature in adipose tissue, especially in association with
      obesity comorbidies. The novel adipokine acylation stimulating protein (ASP) is
      one factor implicated in the inflammatory response. The disruption of the alpha7
      nicotine acetylcholine receptor (alpha7nAChR), an important component of the
      endogenous non-neural cholinergic defense system, may exacerbate sustained
      inflammatory phenotype. We examined cholinergic regulation of ASP-initiated
      inflammatory response in 3T3-L1 adipocytes. Our results show that preincubation
      of 3T3-L1 cells with alpha7nAChR agonist GTS-21 significantly reduces ASP
      mediated chemokine MCP-1 secretion, which is regulated though nuclear factor
      kappaB (NFkappaB) and signal transducer and activator of transcription 3 (STAT3).
      Treatment of 3T3-L1 cells with GTS-21 significantly reduced NFkappaB activation
      by DNA binding and STAT3 activation by disturbing post-translational
      modification. 

PMID- 25985793
TI  - Stress exposure during the preimplantation period affects blastocyst lineages and
      offspring development.
AB  - We found retardation of preimplantation embryo growth after exposure to maternal
      restraint stress during the preimplantation period in our previous study. In the
      present study, we evaluated the impact of preimplantation maternal restraint
      stress on the distribution of inner cell mass (ICM) and trophectoderm (TE) cells
      in mouse blastocysts, and its possible effect on physiological development of
      offspring. We exposed spontaneously ovulating female mice to restraint stress for
      30 min three times a day during the preimplantation period, and this treatment
      caused a significant increase in blood serum corticosterone concentration.
      Microscopic evaluation of embryos showed that restraint stress significantly
      decreased cell counts per blastocyst. Comparing the effect of restraint stress on
      the two blastocyst cell lineages, we found that the reduction in TE cells was
      more substantial than the reduction in ICM cells, which resulted in an increased
      ICM/TE ratio in blastocysts isolated from stressed dams compared with controls.
      Restraint stress reduced the number of implantation sites in uteri, significantly
      delayed eye opening in delivered mice, and altered their behavior in terms of two
      parameters (scratching on the base of an open field test apparatus, time spent in
      central zone) as well. Moreover, prenatally stressed offspring had significantly
      lower body weights and in 5-week old females delivered from stressed dams, fat
      deposits were significantly lower. Our results indicate that exposure to stress
      during very early pregnancy can have a negative impact on embryonic development
      with consequences reaching into postnatal life. 

PMID- 25985792
TI  - Epidermal growth factor improves developmental competence and embryonic quality
      of singly cultured domestic cat embryos.
AB  - This study examined the influence of EGF on the expression of EGF receptors
      (EGFR) and developmental competence of embryos cultured individually versus those
      cultured in groups. Cat oocytes were in vitro matured and fertilized (IVM/IVF),
      and cleaved embryos were randomly assigned to one of seven culture conditions:
      one group each in which embryos were subjected to group culture supplemented with
      or without 5 ng/ml EGF and five groups in which embryos were subjected to single
      embryo culture supplemented with EGF (0, 5, 25, 50 or 100 ng/ml). Morulae,
      blastocysts and hatching blastocysts were assessed at days 5 and 7; post IVF,
      respectively, and total blastocyst cell numbers were assessed at day 7. Relative
      mRNA expressions of EGFR of 2-4-cell embryos, 8-16-cell embryos, morulae and
      blastocysts cultured in groups or singly with or without EGF supplementation were
      examined. OCT3/4 and Ki67 in blastocysts derived from the group or single-embryo
      culture systems with or without EGF supplementation were localized. A higher rate
      of embryos cultured in groups developed to blastocysts than individually
      incubated cohorts. Although EGF increased blastocyst formation in the single
      embryo culture system, EGF did not affect embryo development in group culture.
      Expression levels of EGFR decreased in morulae and blastocysts cultured with EGF.
      An increased ratio of Ki67-positive cells to the total number of cells in the
      blastocyst was observed in singly cultured embryos in the presence of EGF.
      However, EGF did not affect the expression of OCT3/4. These findings indicate
      that EGF enhanced developmental competence of cat embryos cultured singly by
      stimulating cell proliferation and modulating the EGFR expression at various
      developmental stages. 

PMID- 25985798
TI  - TRUCKs: the fourth generation of CARs.
AB  - INTRODUCTION: Adoptive cell therapy of malignant diseases takes advantage of the
      cellular immune system to recognize and destroy cancer cells. This is
      impressively demonstrated by redirecting T cells with a chimeric antigen receptor
      (CAR) towards CD19, inducing complete and lasting remission of leukemia in more
      than two-thirds of patients in early phase trials. AREAS COVERED: We outline how
      the CAR strategy is highly specific in redirecting T cells towards pre-defined
      target cells, however, reaches its limits when targeting solid tumors with a
      tremendous phenotypic heterogeneity. After initial tumor reduction by CAR T
      cells, antigen-negative cancer cells not recognized by CAR may give rise to tumor
      relapse. The situation may be overcome by CAR-mediated activation of T cells in
      the tumor, releasing inducible IL-12 which augments T-cell activation and
      attracts and activates innate immune cells to eliminate antigen-negative cancer
      cells in the targeted lesion. EXPERT OPINION: CAR T cells with a transgenic
      'payload', so-called TRUCK T cells or the 'fourth-generation' CAR T cells, are
      worthwhile to explore to shape the tumor environment by the inducible release of
      transgenic immune modifiers. Such TRUCK T cells are moreover envisioned to be
      applied in fields beyond cancer therapy including the therapy of virus
      infections, auto-immune diseases or metabolic disorders.

PMID- 25985796
TI  - Kansas City Cardiomyopathy Questionnaire Score Is Associated With Incident Heart
      Failure Hospitalization in Patients With Chronic Kidney Disease Without
      Previously Diagnosed Heart Failure: Chronic Renal Insufficiency Cohort Study.
AB  - BACKGROUND: Chronic kidney disease is a risk factor for heart failure (HF).
      Patients with chronic kidney disease without diagnosed HF have an increased
      burden of symptoms characteristic of HF. It is not known whether these symptoms
      are associated with occurrence of new onset HF. METHODS AND RESULTS: We studied
      the association of a modified Kansas City Cardiomyopathy Questionnaire with newly
      identified cases of hospitalized HF among 3093 participants enrolled in the
      Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at
      baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was
      categorized into quartiles (Q1-4) with the lower scores representing the worse
      symptoms. Multivariable-adjusted repeated measure logistic regression models were
      adjusted for demographic characteristics, clinical risk factors for HF, N
      terminal probrain natriuretic peptide level and left ventricular hypertrophy,
      left ventricular systolic and diastolic dysfunction. Over a mean (+/-SD) follow
      up period of 4.3+/-1.6 years, there were 211 new cases of HF hospitalizations.
      The risk of HF hospitalization increased with increasing symptom quartiles; 2.62,
      1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number
      of annual Kansas City Cardiomyopathy Questionnaire assessments per participant
      was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy
      Questionnaire score was independently associated with higher risk of incident HF
      hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52];
      P=0.001 for Q1 compared with Q4). CONCLUSIONS: Symptoms characteristic of HF are
      common in patients with chronic kidney disease and are associated with higher
      short-term risk for new hospitalization for HF, independent of level of kidney
      function, and other known HF risk factors.

PMID- 25985794
TI  - Smad3 Signaling Promotes Fibrosis While Preserving Cardiac and Aortic Geometry in
      Obese Diabetic Mice.
AB  - BACKGROUND: Heart failure in diabetics is associated with cardiac hypertrophy,
      fibrosis and diastolic dysfunction. Activation of transforming growth factor
      beta/Smad3 signaling in the diabetic myocardium may mediate fibrosis and
      diastolic heart failure, while preserving matrix homeostasis. We hypothesized
      that Smad3 may play a key role in the pathogenesis of cardiovascular remodeling
      associated with diabetes mellitus and obesity. METHODS AND RESULTS: We generated
      leptin-resistant db/db Smad3 null mice and db/db Smad3+/- animals. Smad3
      haploinsufficiency did not affect metabolic function in db/db mice, but protected
      from myocardial diastolic dysfunction, while causing left ventricular chamber
      dilation. Improved cardiac compliance and chamber dilation in db/db Smad3+/-
      animals were associated with decreased cardiomyocyte hypertrophy, reduced
      collagen deposition, and accentuated matrix metalloproteinase activity.
      Attenuation of hypertrophy and fibrosis in db/db Smad3+/- hearts was associated
      with reduced myocardial oxidative and nitrosative stress. db/db Smad3 null mice
      had reduced weight gain and decreased adiposity associated with attenuated
      insulin resistance, but also exhibited high early mortality, in part, because of
      spontaneous rupture of the ascending aorta. Ultrasound studies showed that both
      lean and obese Smad3 null animals had significant aortic dilation. Aortic
      dilation in db/db Smad3 null mice occurred despite reduced hypertension and was
      associated with perturbed matrix balance in the vascular wall. CONCLUSIONS: Smad3
      mediates diabetic cardiac hypertrophy, fibrosis, and diastolic dysfunction, while
      preserving normal cardiac geometry and maintaining the integrity of the vascular
      wall.

PMID- 25985800
TI  - Presenilin 1 is necessary for neuronal, but not glial, EGFR expression and
      neuroprotection via gamma-secretase-independent transcriptional mechanisms.
AB  - Epidermal growth factor receptor (EGFR) plays pivotal roles in cell
      proliferation, differentiation, and tissue development, while EGFs protect
      neurons from toxic insults by binding EGFR and stimulating survival signaling.
      Furthermore, recent evidence implicates this receptor in neurometabolic disorders
      like Alzheimer disease and aging. Here we show that absence of presenilin 1 (PS1)
      results in dramatic decrease (>95%) of neuronal EGFR and that PS1-null (PS1(-/-))
      brains have reduced amounts of this receptor. PS1(-/-) cortical neurons contain
      little EGFR and show no epidermal growth factor-induced survival signaling or
      protection against excitotoxicity, but exogenous EGFR rescues both functions even
      in absence of PS1. EGFR mRNA is greatly reduced (>95%) in PS1(-/-) neurons, and
      PS1(-/-) brains contain decreased amounts of this mRNA, although PS1 affects the
      stability of neither EGFR nor its mRNA. Exogenous PS1 increases neuronal EGFR
      mRNA, while down-regulation of PS1 decreases this mRNA. These effects are neuron
      specific, as PS1 affects the EGFR of neither glial nor fibroblast cells. In
      addition, PS1 controls EGFR through novel mechanisms shared with neither gamma
      secretase nor PS2. Our data reveal that PS1 functions as a positive
      transcriptional regulator of neuronal EGFR controlling its expression in a cell
      specific manner. Severe downregulation of EGFR may contribute to developmental
      abnormalities and lethal phenotype found in PS1, but not PS2, null mice.
      Furthermore, PS1 may affect neuroprotection and Alzheimer disease by controlling
      survival signaling of neuronal EGFR.

PMID- 25985804
TI  - Sperm of the giant grouper: cryopreservation, physiological and morphological
      analysis and application in hybridizations with red-spotted grouper.
AB  - In order to develop excellent germplasm resources for giant grouper (Epinephelus
      lanceolatus), cryopreservation of giant grouper sperm was examined in the present
      study. Firstly, 13 kinds of sperm dilution (ELS1-3, EM1-2, TS-2, MPRS, ELRS0-6)
      were prepared with physiological salt, sucrose, glucose and fetal bovine serum.
      The physiological parameters of ELRS3 (ratio of fast motion, ratio of slow
      motion, time of fast motion, time of slow motion, lifespan and motility) and ELS3
      (sperm ratio of slow motion, time of slow motion and motility) were significantly
      higher than those of the other dilutions (P < 0.05). Secondly, after adding 15%
      DMSO and 10% FBS to ELRS3 and ELS3, most physiological parameters of frozen sperm
      were also significantly higher than the other gradients (P < 0.05), and sperm
      motility was as high as 63.68 +/- 4.16% to74.75 +/- 12.71% (fresh sperm motility,
      80.70 +/- 1.37% to 80.71 +/- 1.49%). Mixed with the above dilutions, a final
      volume of 105 ml semen was cryopreserved. Finally, the sperm of giant grouper
      cryopreserved with cryoprotectants (ELRS3 + 15% DMSO + 10% FBS) was used for
      electron-microscopic observation and crossbreeding with red-spotted groupers
      (Epinephelus akaara). The electron-microscopic observation revealed that part of
      the frozen-thawed sperm was cryodamaged, e.g., flagellum fracturing and
      mitochondria falling out, while the ultrastructure of sperm membrane,
      mitochondria and flagellum remained intact. Also, the fertilization and
      hatchability rates of giant grouper frozen sperm and red-spotted grouper eggs
      were as high as 94.56% and 75.56%, respectively. Thus, a technique for
      cryopreservation of giant grouper sperm was successfully developed and applied to
      crossbreeding with red-spotted grouper eggs. 

PMID- 25985803
TI  - Comprehensive Metabolic Profiling of Age-Related Mitochondrial Dysfunction in the
      High-Fat-Fed ob/ob Mouse Heart.
AB  - The ectopic deposition of fat is thought to lead to lipotoxicity and has been
      associated with mitochondrial dysfunction and diabetic cardiomyopathy. We have
      measured mitochondrial respiratory capacities in the hearts of ob/ob and wild
      type mice on either a regular chow (RCD) or high-fat (HFD) diet across four age
      groups to investigate the impact of diet and age on mitochondrial function
      alongside a comprehensive strategy for metabolic profiling of the tissue.
      Myocardial mitochondrial dysfunction was only evident in ob/ob mice on RCD at 14
      months, but it was detectable at 3 months on the HFD. Liquid chromatography-mass
      spectrometry (LC-MS) was used to study the profiles of acylcarnitines and the
      accumulation of triglycerides, but neither class of lipid was associated with
      mitochondrial dysfunction. However, a targeted LC-MS/MS analysis of markers of
      oxidative stress demonstrated increases in GSSG/GSH and 8-oxoguanine, in addition
      to the accumulation of diacylglycerols, which are lipid species linked to
      lipotoxicity. Our results demonstrate that myocardial mitochondria in ob/ob mice
      on RCD maintained a similar respiratory capacity to that of wild type until a
      late stage in aging. However, on a HFD, unlike wild-type mice, ob/ob mice failed
      to increase mitochondrial respiration, which may be associated with a complex I
      defect following increased oxidative damage. 

PMID- 25985799
TI  - Sphingosine 1-phosphate is a ligand for peroxisome proliferator-activated
      receptor-gamma that regulates neoangiogenesis.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive lipid that can function both
      extracellularly and intracellularly to mediate a variety of cellular processes.
      Using lipid affinity matrices and a radiolabeled lipid binding assay, we reveal
      that S1P directly interacts with the transcription factor peroxisome proliferator
      activated receptor (PPAR)gamma. Herein, we show that S1P treatment of human
      endothelial cells (ECs) activated a luciferase-tagged PPARgamma-specific gene
      reporter by ~12-fold, independent of the S1P receptors. More specifically, in
      silico docking, gene reporter, and binding assays revealed that His323 of the
      PPARgamma ligand binding domain is important for binding to S1P. PPARgamma
      functions when associated with coregulatory proteins, and herein we identify that
      peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC1)beta binds
      to PPARgamma in ECs and their progenitors (nonadherent endothelial forming cells)
      and that the formation of this PPARgamma:PGC1beta complex is increased in
      response to S1P. ECs treated with S1P selectively regulated known PPARgamma
      target genes with PGC1beta and plasminogen-activated inhibitor-1 being increased,
      no change to adipocyte fatty acid binding protein 2 and suppression of CD36. S1P
      induced in vitro tube formation was significantly attenuated in the presence of
      the PPARgamma antagonist GW9662, and in vivo application of GW9662 also reduced
      vascular development in Matrigel plugs. Interestingly, activation of PPARgamma by
      the synthetic ligand troglitazone also reduced tube formation in vitro and in
      vivo. To support this, Sphk1(-/-)Sphk2(+/-) mice, with low circulating S1P
      levels, demonstrated a similar reduction in vascular development. Taken together,
      our data reveal that the transcription factor, PPARgamma, is a bona fide
      intracellular target for S1P and thus suggest that the S1P:PPARgamma:PGC1beta
      complex may be a useful target to manipulate neovascularization.

PMID- 25985802
TI  - Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss.
AB  - The alcohol-induced depletion of hepatic retinoid stores correlates with the
      progression of liver injury; however, the mechanisms underlying alcohol's effects
      have not been fully elucidated. Our goal was to gain a mechanistic understanding
      of alcohol-induced hepatic retinoid depletion. Wild-type and mutant mice were
      continuously fed alcohol through Lieber-DeCarli liquid diets, with matched
      control animals pair fed an isocaloric alcohol-free diet to ensure equal nutrient
      and calorie intake between groups. A systematic analysis of tissue retinol and
      retinyl ester levels was performed with HPLC, complemented by gene and protein
      expression analyses. Our results delineated 2 phases of alcohol-induced depletion
      of hepatic retinoid. Initially, ~15% of hepatic retinoid content was mobilized
      from the liver, causing extrahepatic tissue retinoid levels to increase.
      Subsequently, there was a precipitous drop in hepatic retinoid content (>60%),
      without further retinoid accumulation in the periphery. Follow-up studies in
      mutant mice revealed roles for RBP, CRBP1, and CD36 in retinoid mobilization and
      extrahepatic retinoid uptake, as well as a role for CYP2E1 in the catabolism of
      hepatic retinoid. In summary, alcohol has a biphasic effect on hepatic retinoid
      stores, characterized by an initial phase of rapid mobilization to extrahepatic
      tissues followed by extensive catabolism within the liver.

PMID- 25985801
TI  - Absence of nicotinic acetylcholine receptor alpha7 subunit amplifies inflammation
      and accelerates onset of fibrosis: an inflammatory kidney model.
AB  - Inflammation is regulated by endogenous mechanisms, including anti-inflammatory
      cytokines, adenosine, and the nicotinic acetylcholine receptor alpha7 subunit
      (alpha7nAChR). We investigated the role of alpha7nAChR in protection against the
      progression of tissue injury in a model of severe, macrophage-mediated, cytokine
      dependent anti-glomerular basement membrane (GBM) glomerulonephritis (GN), in
      alpha7nAChR-deficient (alpha7(-/-)) mice . At d 7 after the injection of anti-GBM
      antibody, kidneys from alpha7(-/-) mice displayed severe glomeruli (P < 0.0001)
      and tubulointerstitial lesions (P < 0.001) compared to kidneys from WT mice. An
      important finding was the presence of severe glomerulosclerosis in alpha7(-/-)
      mice in this early phase of the disease. Kidneys of alpha7(-/-) mice showed
      greater accumulation of inflammatory cells and higher expression of chemokines
      and cytokines than did those of WT mice. In addition, in alpha7(-/-) fibrotic
      kidneys, the expression of fibrin, collagen, TGF-beta, and tissue inhibitor of
      metalloproteinase (TIMP)-2 increased, and the expression of TIMP3 declined. The
      increase in counterregulatory responses to inflammation in alpha7(-/-) nephritic
      kidneys did not compensate for the lack of alpha7nAChR. These findings indicate
      that alpha7nAChR plays a key role in regulating the inflammatory response in anti
      GBM GN and that disruption of the endogenous protective alpha7nAChR amplifies
      inflammation to accelerate kidney damage and fibrosis.

PMID- 25985805
TI  - Positive subjective measures in abuse liability studies and real-world nonmedical
      use: Potential impact of abuse-deterrent opioids on rates of nonmedical use and
      associated healthcare costs.
AB  - OBJECTIVE: To quantify the potential impact of reductions in positive subjective
      measures from human abuse liability studies on real-world rates of nonmedical use
      of prescription drugs and associated healthcare resource utilization and costs.
      DESIGN: Positive subjective endpoints "overall drug liking," in-the-moment "drug
      liking," and "drug high" Emaxs (peak effects) were recorded from published
      studies. Nonmedical use data were obtained from the 2010 National Survey on Drug
      Use and Health (NSDUH) and Drug Abuse Warning Network surveys. Multivariate
      regressions evaluated the association between the positive subjective endpoints
      and nonmedical use rates, controlling for prescription volume, whether the drug
      is an opioid, and controlled substance schedule. A published budget-impact model
      was used to assess healthcare resource utilization and cost impacts of abuse
      deterrent opioid formulations. RESULTS: A five-point reduction in overall drug
      liking/drug liking/drug high Emax was associated with a 0.25/0.10/0.05 (standard
      errors: 0.11/0.12/0.07) percentage point decrease in the NSDUH lifetime
      nonmedical use rates. Those decreases yielded a 11.3/4.2/2.1 percent reduction
      compared to the samples' lifetime nonmedical use rates of 2.21/2.38/2.36 percent.
      On the basis of a number of assumptions, these reductions were associated with
      private payer cost reductions for a morphine and oxycodone abuse-deterrent
      formulation in the ranges of $147.9-324.1 million and $230.7-958.7 million,
      respectively. CONCLUSIONS: Reductions in overall drug liking were significantly
      associated with reduced real-world nonmedical use, healthcare utilization, and
      costs. Associations using drug high and drug liking were directionally consistent
      with this finding though not statistically significant. A reduction in positive
      subjective measures associated with an abuse-deterrent formulation has potential
      to reduce abuse and associated healthcare utilization and costs.

PMID- 25985806
TI  - Does tapentadol affect sex hormone concentrations differently from morphine and
      oxycodone? An initial assessment and possible implications for opioid-induced
      androgen deficiency.
AB  - OBJECTIVES: Opioid-induced androgen deficiency (OPIAD) affects patients treated
      with opioid analgesics. The norepinephrine reuptake inhibitor (NRI) and u-opioid
      receptor (MOR) agonist activities of tapentadol may result in tapentadol having
      less effect on serum androgen concentrations than analgesics acting through the
      MOR alone, such as morphine and oxycodone. The objectives of this publication are
      to 1) evaluate the effects of tapentadol (NUCYNTA and NUCYNTA extended release
      [ER]) on sex hormone concentrations in healthy male volunteers (vs placebo and
      morphine) and patients with osteoarthritis (vs placebo and oxycodone), and 2)
      present a mechanistic hypothesis explaining how the combined MOR agonist and NRI
      activities of tapentadol may result in less impact on androgen concentrations.
      METHODS: Three clinical studies were conducted: study 1 (single-dose comparison
      study vs morphine in healthy volunteers), study 2 (single-dose-escalation study
      in healthy volunteers without an active comparator), and study 3 (multiple-dose
      study vs oxycodone in patients with osteoarthritis). Studies 1 and 2 were
      conducted at medical research centers in Germany and the United Kingdom; study 3
      was conducted at primary and secondary care centers and medical research centers
      in the United States. All three studies were randomized, double blind, and
      placebo controlled. Concentrations of testosterone, luteinizing hormone (LH), and
      follicle-stimulating hormone (FSH; study 3 only) were evaluated at 6 and 24 hours
      postdose in studies 1 and 2, respectively, and at varying time points postdose in
      study 3. RESULTS: In study 1, mean serum total testosterone concentrations in
      healthy male volunteers were similar at baseline for all treatment periods; 6
      hours after dosing, mean concentrations were comparable between placebo (8.6
      nmol/L) and tapentadol immediate release (IR; 43 mg, 8.8 nmol/L; 86 mg, 9.3
      nmol/L), but were lower following administration of morphine IR 30 mg (5.4
      nmol/L). In study 2, there were no or minimal changes in testosterone in the
      therapeutic dose range with tapentadol IR (75-100 mg), and there was a modest
      decrease that appeared to level off in the supratherapeutic range (125-175 mg);
      mean testosterone and LH concentrations with all doses remained within normal
      ranges (testosterone, 4.56-28.2 nmol/L; LH, 2.9-4.6 U/L). In study 3, the
      decrease in the mean [standard deviation] testosterone concentration from
      baseline to endpoint for male patients receiving tapentadol ER (100 mg, -1.9
      [0.71] nmol/L; 200 mg, -2.1 [0.93] nmol/L) was numerically smaller compared to
      oxycodone CR (20 mg, -2.7 [0.93] nmol/L), but higher compared to placebo (-0.3
      [1.62] nmol/L). CONCLUSIONS: These results suggest that tapentadol, which has
      combined MOR and NRI activities, may have a lower impact on sex hormone
      concentrations than pure opioid analgesics, such as morphine or oxycodone. The
      data and mechanistic rationale presented herein provide a justification for
      conducting additional hypothesis testing studies, and are not intended to be used
      as a basis for clinical decision making. Future studies may help elucidate
      whether the observed trends are clinically significant and would translate into a
      reduced incidence of OPIAD.

PMID- 25985807
TI  - Communication about opioid versus nonopioid analgesics in the emergency
      department.
AB  - OBJECTIVE: The Medication Communication Index (MCI) was used to compare
      counseling about opioids to nonopioid analgesics in the Emergency Department (ED)
      setting. DESIGN: Secondary analysis of prospectively collected audio recordings
      of ED patient visits. SETTING: Urban, academic medical center (>85,000 annual
      patient visits). PARTICIPANTS: Patient participants aged >18 years with one of
      four low acuity diagnoses: ankle sprain, back pain, head injury, and laceration.
      ED clinician participants included resident and attending physicians, nursing
      staff, and ED technicians. MAIN OUTCOME MEASURES: The MCI is a five-point index
      that assigns points for communicating the following: medication name (1), purpose
      (1), duration (1), adverse effects (1), number of tablets (0.5), and frequency of
      use (0.5). Recording transcripts were scored with the MCI, and total scores were
      compared between drug classes. RESULTS: The 41 patients received 56 prescriptions
      (27 nonopioids, 29 opioids). Nonopioid median MCI score was 3 and opioid score
      was 4.5 (p=0.0008). Patients were counseled equally about name (nonopioid 100
      percent, opioid 96.6 percent, p=0.34) and purpose (88.9 percent, 89.7 percent,
      p=0.93). However, patients receiving opioids were counseled more frequently about
      duration of use (nonopioid 40.7 percent, opioid 69.0 percent, p=0.03) and adverse
      effects (18.5 percent, 93.1 percent, p<0.001). In multivariable analysis, opioids
      (beta=0.54, p=0.04), number of medications prescribed (beta=-0.49, p=0.05), and
      time spent in the ED (beta=0.007, p=0.006) were all predictors of total MCI
      score. CONCLUSIONS: The extent of counseling about analgesic medications in the
      ED differs by drug class. When counseling patients about all analgesic
      medications, providers should address not only medication name and purpose but
      also the less frequently covered topics of medication dosing, timing, and adverse
      effects.

PMID- 25985808
TI  - Opioid regimens in patients with chronic pain with multiple cytochrome P450
      defects.
AB  - There is a subgroup of patients with chronic pain who have multiple cytochrome
      P450 enzyme defects. These patients tend to use opioids that are not metabolized
      by the CYP450 system and most apparently require a higher than average dosage. A
      significant number require nonoral administration. 

PMID- 25985809
TI  - Daily home opioid use in adults with sickle cell disease: The PiSCES project.
AB  - BACKGROUND: Although opioid prescribing in sickle cell disease (SCD) can be
      controversial, little is published about patterns of opioid use. OBJECTIVE: To
      report on home opioid use among adults with SCD. DESIGN: Cohort study.
      PARTICIPANTS: Adults with SCD (n=219) who completed daily pain diaries for up to
      6 months and had at least one home pain day. MAIN MEASURES: Use of long-acting or
      short-acting opioids, other analgesics, or adjuvants; the proportion of home
      days, home pain days, and home crisis days with opioid use; these two outcomes
      according to patient characteristics. KEY RESULTS: Patients used opioids on
      12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent)
      used long-acting opioids with or without short-acting opioids and 103 (47.0
      percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used
      only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain
      intensity and pain frequency were higher among opioid users (analysis of variance
      [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even
      when controlling for mean pain on pain days. Among all patients, significant
      relationships were found between any opioid use and somatic symptom burden, SCD
      stress, negative coping, and physical and mental quality of life (QOL); the
      relationship with SCD stress and physical QOL remained when controlled for mean
      pain. Among opioid users, similar associations were found between frequency of
      opioid use and some disease-related and psychosocial variables. CONCLUSIONS: In
      this adult SCD sample, opioids were used by the majority of patients. Pain was
      the overwhelming characteristic associated with use, but disease-related and
      psychosocial variables were also associated.

PMID- 25985810
TI  - Hypogonadism associated with long-term opioid therapy: A systematic review.
AB  - BACKGROUND: Sexual dysfunction and Opioid-Induced Sexual Hormone Deficiency
      (OPISHD) have been associated with patients on long-term opioid pain therapy.
      There have been few comprehensive reviews to establish a relation between
      hypogonadism with chronic opioid pain management. The OPISHD is often not treated
      and literature guiding this topic is scarce. OBJECTIVE: To investigate
      hypogonadism associated with long-term opioid therapy based on qualitative data
      analysis of the available literature. STUDY DESIGN: Systematic review.
      INTERVENTIONS: The review included relevant literature identified through
      searches of PubMed, Cochrane, Clinical Trials, US National Guideline
      Clearinghouse, and EMBASE, for the years 1960 to September 2013. The quality
      assessment and clinical relevance criteria used were the Cochrane Musculoskeletal
      Review Group Criteria for randomized control trials and the Newcastle-Ottawa
      Scale Criteria for observational studies. The level of evidence was classified as
      good, fair, and poor, based on the quality of evidence. MAIN OUTCOME MEASURES:
      The primary outcome measures were clinical symptoms and laboratory markers of
      hypogonadism. Secondary outcome measure was management of OPISHD. RESULTS: Thirty
      one studies were identified, of which 14 studies met inclusion criteria. There
      were no randomized control trials and eight of 14 studies were of moderate
      quality. The remaining studies were of poor quality. Four studies report most
      patients on long-term oral opioid therapy have associated hypogonadism and three
      studies of patients receiving intrathecal opioid therapy suggest that
      hypogonadism is common. CONCLUSIONS: There is lack of high-quality studies to
      associate chronic opioid pain management with hypogonadism. At present, there is
      fair evidence to associate hypogonadism with chronic opioid pain management, and
      only limited evidence for treatment of OPISHD.

PMID- 25985811
TI  - Radiotherapy in early stage follicular lymphoma: is it really the gold standard?

PMID- 25985813
TI  - Brodalumab -an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis.
AB  - INTRODUCTION: IL-17 is a growing target for autoimmune and inflammatory diseases.
      Brodalumab is a fully human anti-IL-17RA monoclonal antibody that has been
      investigated in a range of disease including psoriasis, psoriatic arthritis,
      rheumatoid arthritis, inflammatory bowel disease and asthma. AREAS COVERED: This
      review aims to summarize up-to-date pharmacological properties of brodalumab and
      the clinical efficacy and safety data presented in clinical trials. The focus of
      this review will be on psoriasis, psoriatic arthritis and rheumatoid arthritis
      although we will briefly touch on the other indications in which the drug has
      been studied as we feel it adds to our understanding of the IL-17 pathway and
      highlights areas where research is still needed. EXPERT OPINION: Brodalumab has
      shown good efficacy in psoriasis in small but extended studies with a moderate
      effect on psoriatic arthritis. Brodalumab studies are clearly negative in
      rheumatoid arthritis and inflammatory bowel disease. The data are equivocal in
      asthma; however, further studies in this disease are justifiable. The safety
      profile of this drug thus far is not worrisome although longer studies in more
      patients are needed.

PMID- 25985812
TI  - Strategies to circumvent humoral immunity to adeno-associated viral vectors.
AB  - INTRODUCTION: Recent success in gene therapy of certain monogenic diseases in the
      clinic has infused enthusiasm into the continued development of recombinant adeno
      associated viral (AAV) vectors as next-generation biologics. However, progress in
      clinical trials has also highlighted the challenges posed by the host humoral
      immune response to AAV vectors. Specifically, while pre-existing neutralizing
      antibodies (NAbs) limit the cohort of eligible patients, NAb generation following
      treatment prevents vector re-dosing. AREAS COVERED: In this review, we discuss a
      spectrum of complementary strategies that can help circumvent the host humoral
      immune response to AAV. EXPERT OPINION: Specifically, we present a dual
      perspective, that is, vector versus host, and highlight the clinical attributes,
      potential caveats and limitations as well as complementarity associated with the
      various approaches.

PMID- 25985814
TI  - Blinatumomab: enlisting serial killer T-cells in the war against hematologic
      malignancies.
AB  - INTRODUCTION: The approval of blinatumomab signals the long awaited arrival of
      immunotherapy for acute lymphoblastic leukemia (ALL). Previous options for
      relapsed or refractory disease were restricted to cytotoxic chemotherapy with
      limited efficacy and significant toxicity. Through an innovative mechanism of
      action, blinatumomab stimulates a polyclonal antitumor T-cell response, yielding
      unprecedented single agent efficacy in the relapsed/refractory setting. Success
      comes at the cost of immunological toxicities rarely encountered with previous
      therapies and challenging administration logistics requiring clinical expertise.
      AREAS COVERED: All published clinical and preclinical studies using blinatumomab
      were reviewed in addition to all registered ongoing clinical trials and data
      published in abstract form. The search was limited to the English language. The
      pharmacology, clinical efficacy, toxicity profile, and logistical considerations
      for drug administration are discussed. EXPERT OPINION: Blinatumomab is an
      exciting addition to the treatment armamentarium for relapsed/refractory ALL, yet
      several questions remain regarding optimal implementation into the current
      treatment paradigm. A unique toxicity profile should be weighed against promising
      benefits in a poor prognosis population. Other emerging therapies, such as
      chimeric antigen receptor-modified T-cells and inotuzumab ozogamicin, with
      different side effect profiles and administration schedules, may prove to be more
      beneficial for specific patient populations.

PMID- 25985817
TI  - Alteration of somatostatin receptor 2 expression in canine mammary gland tumor.
AB  - Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in
      human breast cancer. Since there is little information about SSTR2 in canine
      mammary gland tumor (MGT), we clarified its distribution and expression level in
      normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined
      by immunohistochemical staining was observed in the cytoplasm of luminal
      epithelial cells. The intensity was negatively correlated with malignancy: normal
      tissues and some of the benign tumors had the highest levels, while the malignant
      tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2
      protein level in benign tumors was significantly lower than the normal mammary
      gland. On the other hand, SSTR2 protein levels in two of three malignant tumors
      were higher than the other groups. These results suggest that SSTR2 expression
      alters according to the malignancy of canine MGT. 

PMID- 25985818
TI  - Melatonin redox activity. Its potential clinical applications in
      neurodegenerative disorders.
AB  - Neurodegeneration is the hallmark of many chronic progressive neurogical
      disorders characterized by specific clinical, morphological and biochemical
      features. Central nervous system is very sensitive to oxidative stress, which is
      considered as a key factor of neurodegenerative disorders. Therefore, many
      therapeutical strategies are focused on molecules with redox activity to re
      establish the equilibrium between pro and antioxidants. Due to the fact that
      melatonin readily crosses the blood- brain-barrier, concomitant with its safety
      profile at the highest dosages makes this dietary supplement very useful in
      possible clinical application in neurodegeneration. Melatonin is currently
      marketed in several countries as a dietary supplement with no prescription.
      Clinical trials have shown different effectiveness of melatonin supplementation
      in several disorders, including neurodegenerative disorders. Melatonin has unique
      biochemical properties such as scavenging of hydroxyl, carbonate, alkoxyl,
      peroxyl and aryl cation radicals and stimulation of activities main antioxidative
      enzymes (glutathione peroxidase, superoxide dismutase etc.). Moreover, it can
      suppress nitric oxide synthase. The present paper highlighted the potential
      clinical role of melatonin in main neurodegenerative diseases including Alzheimer
      disease, Parkinson disease, amylotrophic lateral sclerosis and multiple
      sclerosis. Moreover, in this review the main molecular aspects of melatonin in
      brain cell protection and survival mechanisms were discussed. Therefore,
      melatonin is regarded as a potential therapeutical agent in clinical application
      in neurodegenerative disorders, but this findings needs to be confirmed by the
      larger, more well-designed clinical trials. 

PMID- 25985816
TI  - Prevalence of amyloid deposition in mature healthy chickens in the flock that
      previously had outbreaks of vaccine-associated amyloidosis.
AB  - Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic
      inflammation, such as that caused by bacterial infection. We previously described
      vaccine-associated AA amyloidosis in juvenile chickens. In this study, the
      prevalence of amyloid deposition was measured in mature healthy chickens that
      survived a previous outbreak of avian AA amyloidosis while they were juveniles.
      Herein, we analyzed the amyloid deposition in mature chickens and compared the
      prevalence of amyloid deposition with juvenile chickens obtained in our previous
      study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver
      was absent in mature chickens, while juvenile chickens had a rate of 24%; 2)
      amyloid deposition in the spleen was observed in 36% of juvenile chickens and in
      40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature
      chickens (43.75%) was approximately half that of juvenile chickens (88%). These
      results suggest that additional amyloid deposition in chickens previously exposed
      to AA amyloidosis may not worsen with age. Further, amyloid deposition in
      chickens may tend to regress when causative factors, such as vaccinations and/or
      chronic inflammation, are absent. 

PMID- 25985819
TI  - Editorial: pharmacological considerations in anesthesiology- from organ failure
      to transplantation.

PMID- 25985820
TI  - Anesthetic pharmacology and perioperative considerations for heart
      transplantation.
AB  - From uncertain beginnings over four decades ago, heart transplantation is now the
      definitive therapy for end-stage heart failure. This review will attempt to
      comprehensively cover the broad gamut of anesthetic, hemodynamic, antimicrobial,
      immunosuppressive and hemostatic agents used by the cardiothoracic
      anesthesiologist in the perioperative management of patients with endstage heart
      disease. 

PMID- 25985821
TI  - Structure and Reactivity of Alucone-Coated Films on Si and Li(x)Si(y) Surfaces.
AB  - Coating silicon particles with a suitable thin film has appeared as a possible
      solution to accommodate the swelling of silicon upon lithiation and its posterior
      cracking and pulverization during cycling of Li-ion batteries. In particular,
      aluminum alkoxide (alucone) films have been recently deposited over Si anodes,
      and the lithiation and electrochemical behavior of the system have been
      characterized. However, some questions remain regarding the lithium molecular
      migration mechanisms through the film and the electronic properties of the
      alucone film. Here we use density functional theory, ab initio molecular dynamics
      simulations, and Green's function theory to examine the film formation,
      lithiation, and reactivity in contact with an electrolyte solution. It is found
      that the film is composed of Al-O complexes with 3-O or 4-O coordination. During
      lithiation, Li atoms bind very strongly to the O atoms in the most energetically
      favorable sites. After the film is irreversibly saturated with Li atoms, it
      becomes electronically conductive. The ethylene carbonate molecules in liquid
      phase are found to be reduced at the surface of the Li-saturated alucone film
      following similar electron transfer mechanisms as found previously for lithiated
      silicon anodes. The theoretical results are in agreement with those from
      morphology and electrochemical analyses. 

PMID- 25985822
TI  - Induction of chondrogenic differentiation of mouse embryonic mesenchymal stem
      cells through an in vitro pellet model.
AB  - This study employed transforming growth factor beta 3 (TGF-beta3) induction of
      the C3H10T1/2 mesenchymal stem cell (MSC) line to construct an in vitro
      chondrogenic differentiation model for MSCs. A C3H10T1/2 MSC cell line was
      cultured, amplified, and the seventh generation of cells was centrifuged to
      construct pellets, which were divided into a non-induced group and an induced
      group (treated with TGF-beta3, vitamin C, dexamethasone, and ITS). Specimens were
      taken after 7, 14, 21, and 28 days under non-induced and induced culture to
      compare these two groups by Alcian Blue staining, collagen type II
      immunohistochemical staining, and transmission election microscopy (TEM) on days
      21 and 42. Cell pellets in the non-induced group were smaller than those in the
      induced group on days 7, 14, 21, and 28 with the pellet morphology of the induced
      group being more regular and nearly spherical. Alcian blue staining in the
      induced group was consistently stronger than that in non-induced group across all
      time points, and type II collagen immunohistochemical IOD values were
      significantly higher in the induced group over the non-induced group across all
      time points. On days 21 and 42, TEM revealed that the induced group displayed
      greater karyokinesis and a higher euchromatin ratio compared to the non-induced
      group. This specially constructed pellet model treated with TGF-beta3-containing
      chondrogenic medium can effectively promote chondrogenic differentiation of
      C3H10T1/2 MSC cells in vitro. This in vitro pellet model should be of value in
      providing a preliminary cell model reference for further studies of the mechanism
      of chondroblast differentiation of stem cells. 

PMID- 25985823
TI  - CO2 as a regulator for the controllable preparation of highly dispersed chitosan
      supported Pd catalysts in ionic liquids.
AB  - A controllable synthetic route has been developed for the preparation of chitosan
      supported Pd catalysts in an ionic liquid, 1-butyl-3-methylimidazolium acetate
      ([Bmim]OAc), by using compressed CO2 as the anti-solvent and regulator. It was
      found that the dispersion of Pd particles on chitosan and the catalytic activity
      of the as-prepared catalysts for the hydrogenation of styrene could be tuned by
      changing the pressure of CO2. 

PMID- 25985824
TI  - Development of a microparticulate prostate cancer vaccine and evaluating the
      effect of route of administration on its efficacy via the skin.
AB  - The skin has been identified as a promising target to deliver vaccines. In this
      study, prostate cancer antigens were delivered in a spray-dried microparticulate
      carrier to a murine model via the transdermal route and the subcutaneous route.
      There was a significant increase in the humoral responses as determined by the
      total serum IgG titres (p < 0.05) and the cellular responses as determined by the
      T- and B-cells sub-population in spleen samples and delay in tumour growth till 8
      weeks post-tumour challenge of both vaccinated groups when compared to the
      controls. The vaccine microparticles administered via the transdermal route
      induced a Th2-mediated immune response versus a mixed Th1- and Th2-mediated
      immune response via the subcutaneous route. Thus, the particulate vaccine
      delivery system proves to be a promising alternative for generation of a robust
      immune response against prostate cancer via the skin in a murine model. 

PMID- 25985825
TI  - Female third party lymphocytes are effective for immunotherapy of patients with
      unexplained primary recurrent spontaneous abortion: A retrospective analysis of
      outcomes.
AB  - OBJECTIVES: Allogeneic lymphocytes of paternal origin or supplied by a male third
      party have been used for the treatment of recurrent spontaneous abortion. Few
      studies, however, have examined the use of female third party lymphocytes. Our
      purpose was to determine whether female third party lymphocytes could be used for
      immunotherapy of women with recurrent spontaneous abortion. METHODS: In this
      retrospective non-randomised cohort-controlled study, the medical records of
      patients with three or more spontaneous abortions who received immunotherapy with
      lymphocytes from their partner, a male third party or a female third party, as
      well as those who received no immunotherapy, from 1996 to 2012 were reviewed. All
      patients were negative for mixed lymphocyte culture reaction (MLR)-blocking
      antibodies. Immunotherapy was performed in 302 patients in two courses, while 53
      patients received no immunotherapy. RESULTS: The pregnancy rates in patients who
      received lymphocytes from their partners, a male third party or a female third
      party, and in those not immunised, were 85.6%, 87.3%, 89.7%, and 79.3%,
      respectively (p = 0.523);the live birth rates were 87.3%, 75.8%, 84.6%, and
      40.5%, respectively (p < 0.001). CONCLUSIONS: We conclude that female third party
      lymphocytes can be used for immunotherapy in patients with recurrent spontaneous
      abortion.

PMID- 25985826
TI  - Can prenatal exposure to a 900 MHz electromagnetic field affect the morphology of
      the spleen and thymus, and alter biomarkers of oxidative damage in 21-day-old
      male rats?
AB  - We investigated the effects of a 900 Megahertz (MHz) electromagnetic field (EMF),
      applied during the prenatal period, on the spleen and thymus of 21-day-old male
      rat pups. Pregnant Sprague-Dawley rats were divided into control and EMF groups.
      We applied 900 MHz EMF for 1 h/day to the EMF group of pregnant rats. Newborn
      male rat pups were removed from their mothers and sacrificed on postnatal day 21.
      Spleen and thymus tissues were excised and examined. Compared to the control
      group, thymus tissue malondialdehyde levels were significantly higher in the
      group exposed to EMF, while glutathione levels were significantly decreased.
      Increased malondialdehyde and glutathione levels were observed in splenic tissue
      of rats exposed to EMF, while a significant decrease occurred in superoxide
      dismutase values compared to controls. Transmission electron microscopy showed
      pathological changes in cell morphology in the thymic and splenic tissues of
      newborn rats exposed to EMF. Exposure to 900 MHz EMF during the prenatal period
      can cause pathological and biochemical changes that may compromise the
      development of the male rat thymus and spleen. 

PMID- 25985827
TI  - Synergistic Effect of PEI and PDMAEMA on Transgene Expression in Vitro.
AB  - Polyethylenimine (PEI) and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA)
      have both been used for DNA delivery. PDMAEMA has been shown to exhibit better
      gene transfection efficiency but lower expression ability than PEI. We mixed the
      two polymers at different ratios to investigate whether the resulting "dual"
      polyplex (PEI/PDMAEMA/DNA) could enhance both gene transfection efficiency and
      DNA expression ability. Experimental results showed a significant increase in DNA
      internalization and DNA expression for the PDMAEMA/PEI/DNA polyplexes at a ratio
      of 1:3 or 1:9 (PDMAEMA: PEI), depending on cell type, in comparison with PEI/DNA,
      PDMAEMA/DNA, and PDMAEMA/PEI/DNA at other ratios. PDMAEMA/PEI/DNA polyplexes did
      not reduce cell viability. In contrast to with the conventional approach using
      covalently modified PEI, the proposed "combination" approach provided a more
      convenient and effective way to improve transgene expression efficiency. 

PMID- 25985828
TI  - Hand osteolysis in patients with adult T-cell leukemia-lymphoma: radiographic
      characteristics.
AB  - Adult T-cell leukemia-lymphoma (ATLL) is caused by human T-cell lymphotrophic
      virus I (HTLV-I) infection. Among ATLL cases, 70% of patients present with
      leukemia and the remaining patients present with lymphoma. Hand osteolysis in the
      patients with ATLL is considered as paraneoplastic syndrome and caused by
      parathyroid hormone-related peptide (PTHrP) released from tumor cells.
      Radiographic features are similar to hyperparathyroidism, but the distribution of
      osteolysis in hands appears to be slightly different with the authors'
      experiences. The objective of this study was to identify radiographic
      characteristics of hand osteolysis associated with ATLL. We included six ATLL
      patients (5 men and 1 woman; age range, 45-71 years). All the patients presented
      with acute leukemia, and three were associated with hypercalcemia and pain in
      various locations including hands. Patterns of osteolysis on hand radiographs
      were evaluated and recorded independently by three musculoskeletal radiologists.
      We analyzed the distribution of the bone resorption in the ray distribution of
      the hand, finger predilection, and the difference between the ulnar and radial
      sides. The bone resorption was characterized by frequent involvement of the
      distal and proximal phalanges, predilection of ring fingers and prominent
      involvement on the ulnar side, compared with frequent involvement of proximal and
      middle phalanges, index and middle fingers, and on the radial side in the bone
      resorption of typical hyperparathyroidism. Such distribution may be a
      characteristic feature of hand osteolysis in patients with ATLL. The present
      findings are helpful for physicians to differentiate PTHrP-mediated osteolysis in
      ATLL from parathyroid hormone-mediated hyperparathyroidism. 

PMID- 25985829
TI  - Novosphingobium gossypii sp. nov., isolated from Gossypium hirsutum.
AB  - A Gram-stain-negative, rod-shaped, non-spore-forming bacterium (strain JM
      1396(T)) producing a yellow pigment, was isolated from the healthy internal stem
      tissue of post-harvest cotton (Gossypium hirsutum, cultivar 'DES-119') grown at
      the Plant Breeding Unit at the E.V. Smith Research Center in Tallassee (Macon
      county), AL, USA. 16S rRNA gene sequence analysis of strain JM-1396(T) showed
      high sequence similarity values to the type strains of Novosphingobium
      mathurense, Novosphingobium panipatense (both 98.6%) and Novosphingobium
      barchaimii (98.5%); sequence similarities to all other type strains of species of
      the genus Novosphingobium were below 98.3%. DNA-DNA pairing experiments of the
      DNA of strain JM-1396(T) and N. mathurense SM117(T), N. panipatense SM16(T) and
      N. barchaimii DSM 25411(T) showed low relatedness values of 8% (reciprocal 7%),
      24% (reciprocal 26%) and 19% (reciprocal 25%), respectively. Ubiquinone Q-10 was
      detected as the dominant quinone; the fatty acids C18 : 1omega7c (71.0%) and the
      typical 2-hydroxy fatty acid, C14 : 0 2-OH (11.7%), were detected as typical
      components. The polar lipid profile contained the diagnostic lipids
      diphosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid and
      phosphatidylcholine. The polyamine pattern contained the major compound
      spermidine and only minor amounts of other polyamines. All these data revealed
      that strain JM-1396(T) represents a novel species of the genus Novosphingobium.
      For this reason we propose the name Novosphingobium gossypii sp. nov. with the
      type strain JM-1396(T) ( = LMG 28605(T) = CCM 8569(T) = CIP 110884(T)).

PMID- 25985830
TI  - Marinobacter halophilus sp. nov., a halophilic bacterium isolated from a salt
      lake.
AB  - A Gram-staining-negative bacterium, strain XCD-X12(T), was isolated from
      Xiaochaidan Lake, a salt lake (salinity 9.9%, w/w) in Qaidam basin, Qinghai
      Province, China. Its taxonomic position was determined by using a polyphasic
      approach. Cells of strain XCD-X12(T) were non-spore-forming rods, 0.4-0.7 MUm
      wide, 2.1-3.2 MUm long and motile with a single polar flagellum. Strain XCD
      X12(T) was strictly aerobic and catalase- and oxidase-positive. Growth was
      observed in the presence of 0-20.0% (w/v) NaCl (optimum, 4.0-8.0%), at 4-35 
      degrees C (optimum, 30  degrees C) and at pH 6.5-10.5 (optimum, pH 8.5). It
      contained Q-9 as the predominant respiratory quinone. The major fatty acids
      (>10.0%) were C16 : 0, C16 : 1omega9c and C18 : 1omega9c. The major polar lipids
      were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two
      unknown phospholipids and an uncharacterized aminophospholipid. The DNA G+C
      content was 55.6 mol% (Tm). Phylogenetic trees based on 16S rRNA gene sequences
      showed that strain XCD-X12(T) was associated with the genus Marinobacter, and
      showed the highest 16S rRNA gene sequence similarity to Marinobacter
      hydrocarbonoclasticus ATCC 49840(T) (97.4%), M. vinifirmus FB1(T) (96.8%), M.
      excellens KMM 3809(T) (96.8%) and M. antarcticus ZS2-30(T) (96.7%). DNA-DNA
      relatedness of strain XCD-X12(T) to M. hydrocarbonoclasticus CGMCC 1.7683(T) was
      34 +/- 5%. Based on these data, it is concluded that strain XCD-X12(T) represents
      a novel species of the genus Marinobacter, for which the name Marinobacter
      halophilus sp. nov. is proposed. The type strain is XCD-X12(T) ( = CGMCC
      1.12481(T)= JCM 30472(T)).

PMID- 25985831
TI  - Sphingomonas morindae sp. nov., isolated from Noni (Morinda citrifolia L.)
      branch.
AB  - Two yellow bacterial strains, designated NBD5(T) and NBD8, isolated from Noni
      (Morinda citrifolia L.) branch were investigated using a polyphasic taxonomic
      approach. Cells were Gram-stain-negative, aerobic, non-spore-forming, non-motile
      and short rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences
      suggested that the strains were members of a novel species of the genus
      Sphingomonas, the seven closest neighbours being Sphingomonas oligoaromativorans
      SY-6(T) (96.9% similarity), Sphingomonas polyaromaticivorans B2-7(T) (95.8%),
      Sphingomonas yantingensis 1007(T) (94.9%), Sphingomonas sanguinis IFO 13937(T)
      (94.7%), Sphingomonas ginsenosidimutans Gsoil 1429(T) (94.6%), Sphingomonas
      wittichii RW1(T) (94.6%) and Sphingomonas formosensis CC-Nfb-2(T) (94.5%).
      Strains NBD5T and NBD8 had sphingoglycolipid, phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine as the major
      polar lipids, ubiquinone 10 as the predominant respiratory quinone, and sym
      homospermidine as the major polyamine. Strains NBD5(T) and NBD8 were clearly
      distinguished from reference type strains based on phylogenetic analysis, DNA-DNA
      hybridization, fatty acid composition data analysis, and comparison of a range of
      physiological and biochemical characteristics. It is evident from the genotypic
      and phenotypic data that strains NBD5(T) and NBD8 represent a novel species of
      the genus Sphingomonas, for which the name Sphingomonas morindae sp. nov. is
      proposed. The type strain is NBD5(T) ( = DSM 29151(T) = KCTC 42183(T) = CICC
      10879(T)).

PMID- 25985832
TI  - Sphingomonas lacus sp. nov., an astaxanthin-dideoxyglycoside-producing species
      isolated from soil near a pond.
AB  - Taxonomic studies were performed on an astaxanthin-dideoxyglycoside-producing
      strain, designated PB304(T), isolated from soil near a pond in Daejeon city,
      South Korea. Cells of strain PB304(T) were Gram-staining-negative, strictly
      aerobic, orange-coloured and motile, and occurred as single or paired short
      chains. PB304(T) did not contain bacteriochlorophyll a. 16S rRNA gene sequence
      analysis revealed that strain PB304(T) was closely related to 'Sphingomonas humi'
      KCTC 12341 (98.7%), Sphingomonas kaistensis KCTC 12344(T)(97.9%), Sphingomonas
      astaxanthinifaciens DSM 22298(T) (97.6%) and Sphingomonas ginsengisoli KCTC
      12630(T) (97.5%). Analysis of pufLM gene sequences revealed strain PB304(T) to be
      closely related to 'S. humi' KCTC 12341 (88.1%). The major cellular fatty acids
      were C16 : 0, summed feature 4 (comprising iso-C15 : 0 2-OH and/or C16 :
      1omega7c), and summed feature 7 (comprising C18  : 1omega7c/omega9t/omega12t).
      Ubiquinone 10 (Q-10) was the sole quinone identified, and the major pigment was
      astaxanthin dideoxyglycoside. The major polar lipids were sphingoglycolipid,
      phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol and
      phosphatidylethanolamine. The polyamine was spermidine. The DNA-DNA relatedness
      values of strain PB304(T) with respect to its closest phylogenetic neighbours
      were 57.1% for 'S. humi' KCTC 12341, 51.2% for Sphingomonas kaistensis KCTC
      12334T, 50.6% for Sphingomonas astaxanthinifaciens DSM 22298(T) and 50.2% for
      Sphingomonas ginsengisoli KCTC 12630(T). The DNA G+C content of strain PB304(T)
      was 66.6 mol%. On the basis of the phenotypic, chemotaxonomic and phylogenetic
      data, strain PB304T is concluded to represent a novel species of the genus
      Sphingomonas, for which the name Sphingomonas lacus is proposed. The type strain
      is PB304(T) ( = KCTC 32458(T) = CECT 8383(T)).

PMID- 25985833
TI  - Pseudomonas salina sp. nov., isolated from a salt lake.
AB  - A Gram-staining-negative, facultatively aerobic bacterium, strain XCD-X85(T), was
      isolated from Xiaochaidan Lake, a salt lake (salinity 9.9%, w/v) in Qaidam basin,
      Qinghai province, China. Its taxonomic position was determined by using a
      polyphasic approach. Cells of strain XCD-X85(T) were non-endospore-forming rods,
      0.4-0.6 MUm wide and 1.0-1.6 MUm long, and motile by means of a single polar
      flagellum. Strain XCD-X85(T) was catalase- and oxidase-positive. Growth was
      observed in the presence of 0-12.0% (w/v) NaCl (optimum, 1.0-2.0%) and at 4-35 
      degrees C (optimum, 25-30  degrees C) and pH 6.5-10.5 (optimum, pH 8.0-8.5).
      Strain XCD-X85(T) contained (>10%) summed feature 8 (C18 : 1omega7c and/or C18 :
      1omega6c), C12 : 0, C16 : 0 and summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c) as the predominant fatty acids. The major respiratory quinone was
      ubiquinone 9 (Q-9). The major polar lipids were phosphatidylethanolamine,
      phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content was 57.4
      mol%. Phylogenetic trees based on 16S rRNA gene sequences showed that strain XCD
      X85(T) was associated with the genus Pseudomonas, and showed highest 16S rRNA
      gene sequence similarities to Pseudomonas pelagia CL-AP6(T) (99.0%) and
      Pseudomonas bauzanensis BZ93(T) (96.8%). DNA-DNA relatedness of strain XCD-X85T
      to P. pelagia JCM 15562(T) was 19 +/- 1%. On the basis of the data presented
      above, it is concluded that strain XCD-X85(T) represents a novel species of the
      genus Pseudomonas, for which the name Pseudomonas salina sp. nov. is proposed.
      The type strain is XCD-X85(T) ( = CGMCC 1.12482(T) = JCM 19469(T)).

PMID- 25985834
TI  - Molecular systematics of marine gregarine apicomplexans from Pacific tunicates,
      with descriptions of five novel species of Lankesteria.
AB  - The eugregarines are a group of apicomplexan parasites that mostly infect the
      intestines of invertebrates. The high level of morphological variation found
      within and among species of eugregarines makes it difficult to find consistent
      and reliable traits that unite even closely related lineages. Based mostly on
      traits observed with light microscopy, the majority of described eugregarines
      from marine invertebrates has been classified into a single group, the
      Lecudinidae. Our understanding of the overall diversity and phylogenetic
      relationships of lecudinids is very poor, mainly because only a modest amount of
      exploratory research has been done on the group and very few species of
      lecudinids have been characterized at the molecular phylogenetic level. In an
      attempt to understand the diversity of marine gregarines better, we surveyed
      lecudinids that infect the intestines of Pacific ascidians (i.e. sea squirts)
      using ultrastructural and molecular phylogenetic approaches; currently, these
      species fall within one genus, Lankesteria. We collected lecudinid gregarines
      from six ascidian host species, and our data demonstrated that each host was
      infected by a different species of Lankesteria: (i) Lankesteria hesperidiiformis
      sp. nov., isolated from Distaplia occidentalis, (ii) Lankesteria metandrocarpae
      sp. nov., isolated from Metandrocarpa taylori, (iii) Lankesteria halocynthiae sp.
      nov., isolated from Halocynthia aurantium, (iv) Lankesteria herdmaniae sp. nov.,
      isolated from Herdmania momus, (v) Lankesteria cf. ritterellae, isolated from
      Ritterella rubra, and (vi) Lankesteria didemni sp. nov., isolated from Didemnum
      vexillum. Visualization of the trophozoites with scanning electron microscopy
      showed that four of these species were covered with epicytic folds, whereas two
      of the species were covered with a dense pattern of epicytic knobs. The molecular
      phylogenetic data suggested that species of Lankesteria with surface knobs form a
      clade that is nested within a paraphyletic assemblage species of Lankesteria with
      epicytic folds. 

PMID- 25985835
TI  - Recent advancement of nanostructured carbon for energy applications.

PMID- 25985836
TI  - Graphene Oxide Selectively Enhances Thermostability of Trypsin.
AB  - In the past few years, graphene and its derivative, graphene oxide (GO), have
      been extensively studied for their applications in biotechnology. In our previous
      work, we reported certain PEGylated GOs (GO-PEGs) can selectively promote trypsin
      activity and enhance its thermostability. To further explore this, here we
      synthesized a series of GO-PEGs with varying PEGylation degrees. Enzymatic
      activity assay shows that both GO and GO-PEGs can protect trypsin, but not
      chymotrypsin, from thermal denaturation at high temperature. Surprisingly, the
      lower the PEGylation degree, the better the protection, and GO as well as the GO
      PEG with the lowest PEGylation degree show the highest protection efficiency
      (~70% retained activity at 70  degrees C). Fluorescence spectroscopy analysis
      shows that GO/GO-PEGs have strong interactions with trypsin. Molecular Dynamics
      (MD) simulation results reveal that trypsin is adsorbed onto the surface of GO
      through its cationic residues and hydrophilic residues. Different from
      chymotrypsin adsorbed on GO, the active site of trypsin is covered by GO. MD
      simulation at high temperature shows that, through such interaction with GO,
      trypsin's active site is therefore stabilized and protected by GO. Our work not
      only illustrates the promising potential of GO/GO-PEGs as efficient, selective
      modulators for trypsin, but also provides the interaction mechanism of GO with
      specific proteins at the nano-bio interface. 

PMID- 25985837
TI  - Comparison of glyburide with metformin in treating gestational diabetes mellitus:
      a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Controversy has surrounded the treatment of gestational
      diabetes mellitus (GDM) for a long time. Although the use of both glyburide and
      metformin are recommended as an alternate to insulin if dietary therapy fails in
      GDM patients, it remains unclear whether both drugs are equally safe and
      efficacious. Therefore, in this review we compared the efficacy and safety of
      glyburide with metformin in treating GDM. METHODS: A systematic review and meta
      analysis of randomized controlled trials was conducted that compared the efficacy
      and safety of glyburide with metformin in GDM patients. Electronic databases were
      used to conduct the literature search for study identification along with a hand
      search of pertinent journals and conference proceedings. The effect measure used
      to present the results was risk ratio (RR) with 95% confidence interval (CI). A
      fixed-effects model was used to pool the data if no significant heterogeneity was
      reported and a random-effects model was used in the case of significant
      heterogeneity being reported for an outcome. RESULTS: Three studies involving 508
      patients met the inclusion criteria of this review. A significant increase in the
      risk of the composite outcome, i.e., macrosomia and large for gestational age
      (LGA) births (RR 1.94; 95% CI 1.03-3.66, p = 0.04), was observed in the glyburide
      group, whereas a non-significant increase in the risk of neonatal hypoglycemia
      (RR 1.92; 95% CI 0.31-12.02) was also noticed. Results remained statistically non
      significant for preterm births (RR 0.65; 95% CI 0.24-1.77), neonatal birth weight
      (mean difference (MD) 120.63 g; 95% CI -62.08 to 303.33), and cesarean section
      (RR 0.86; 95% CI 0.55-1.34). A significant decrease in fasting glucose levels (MD
      -2.40 mg/dL; 95% CI -4.60 to -0.21; p = 0.03) was noticed in glyburide group
      while the difference was non-significant for postprandial glucose levels (MD 
      0.84 mg/dL; 95% CI -4.03 to 2.35). CONCLUSION: Metformin seems to be a superior
      choice to glyburide if oral antidiabetic drug therapy is to be initiated in GDM
      patients.

PMID- 25985838
TI  - Clopidogrel versus aspirin in patients with recent ischemic stroke and
      established peripheral artery disease: an economic evaluation in a Chinese
      setting.
AB  - BACKGROUND AND OBJECTIVES: Clopidogrel or aspirin are indicated for patients with
      recent ischemic stroke (IS) or established peripheral artery disease (PAD). We
      compared the cost effectiveness of clopidogrel with that of aspirin in Chinese
      patients with recent IS or established PAD. METHODS: A discrete-event simulation
      was developed to evaluate the economic implications of secondary prevention with
      clopidogrel versus aspirin. All available evidence was derived from clinical
      studies. Costs from a Chinese healthcare perspective in 2013 US dollars and
      quality-adjusted life-years (QALYs) were projected over patients' lifetimes.
      Uncertainties were addressed using sensitivity analyses. RESULTS: Compared with
      aspirin, clopidogrel yielded a marginally increased life expectancy by 0.46 and
      0.21 QALYs at an incremental cost-effectiveness ratio of $US5246 and $US9890 per
      QALY in patients with recent IS and established PAD, respectively. One-way
      sensitivity analyses showed that the evaluation of patients with PAD and recent
      IS was robust except for the parameter of patient age. Given a willingness-to-pay
      of $US19,877 per QALY gained, clopidogrel had a probability of 90 and 68% of
      being cost effective in the recent IS or established PAD subgroups compared with
      aspirin, respectively. CONCLUSIONS: The analysis suggests that clopidogrel for
      secondary prevention is cost effective for patients with either PAD or recent IS
      in a Chinese setting in comparison with aspirin.

PMID- 25985839
TI  - Glomerular cytokine expression in murine lupus nephritis.
AB  - BACKGROUND: Aberrant expression of T helper cell (Th) cytokines is believed to
      play a central role in the pathogenesis of systemic lupus erythematosus (SLE).
      While the glomerulus is one of the major targets of lupus inflammation, little is
      known about the cytokine expression in glomeruli. The current study aimed to
      explore the profiles of Th cytokine gene expressions in isolated glomeruli of
      lupus-prone mice. METHODS: Glomeruli were purified from lupus-prone MRL/lpr mice
      using the magnetic microbead method. Expressions of cytokine genes representing
      the Th subset and FoxP3 were examined using real-time polymerase chain reaction.
      Serum levels of these cytokines were also measured by enzyme-linked immunosorbent
      assay. MRL/n mice were used as controls. Histologic glomerular damages were
      scored semiquantitatively. To examine the role of TNF-alpha in glomerular damage,
      we administered etanercept, a TNF-alpha antagonist, into the subjects. RESULTS:
      Glomerular gene expressions of TNF-alpha in lpr mice increased with week
      postpartum and reached statistically significant levels at 16 weeks compared with
      those of the glomeruli from control mice. Expressions of IFN-gamma, IL-4 and
      FoxP3 also increased, but the difference was not significant. There was a
      significant increase in serum levels of TNF-alpha, IFN-gamma, and IL-17 and
      decrease in those of IL-4. Among the genes examined, TNF-alpha significantly
      correlated with glomerular damage score. Administration of etanercept did not
      affect glomerular cytokine expressions or proteinuria and failed to ameliorate
      histologic glomerular damages. CONCLUSION: Our data suggest that Th1 cytokines,
      especially TNF-alpha, are dominantly expressed in the glomeruli of lupus-prone
      mice, but its pathophysiological role remains unclear.

PMID- 25985840
TI  - Early survival on maintenance dialysis therapy in South Africa: evaluation of a
      pre-dialysis education programme.
AB  - BACKGROUND: Mortality in the first year of maintenance dialysis is higher than in
      subsequent years and, within this first year, the risk of death is highest in the
      first 90 days. Some studies have shown that pre-dialysis education reduces early
      mortality. Limited data have been published from South Africa regarding early
      mortality after commencement of maintenance dialysis treatment and the effect of
      pre-dialysis intervention programmes on these outcomes. The aim of this study was
      to assess the impact of a pre-dialysis intervention programme on 90- and 365-day
      outcomes and to determine incident mortality in a population of chronic haemo-
      and peritoneal dialysis patients in South Africa. METHODS: This study used a
      retrospective cohort of 269 patients who received a pre-dialysis intervention
      [Healthy Start (HS)] and a matched group of 269 patients who did not receive the
      intervention. Both groups subsequently commenced maintenance haemo-/peritoneal
      dialysis with National Renal Care (NRC). A between-group comparative analysis was
      conducted to determine whether there were any differences in morbidity and
      mortality at 90 and 365 days of chronic dialysis treatment. Survival curves for
      the first 365 days of treatment were calculated using the Kaplan-Meier estimation
      for the entire population and by age group, gender, race, diabetes, dialysis
      modality and presence of a central venous catheter (CVC) at start of dialysis
      treatment. RESULTS: There were no significant differences between the HS and non
      HS groups at 90 and 365 days when comparing mortality, cause of death, hospital
      admission rates and length of stay. Data were then pooled and a Kaplan-Meier
      analysis showed 90- and 365-day survival of 96.7 and 85.6%, respectively. The
      peak mortality occurred at 150 days of dialysis treatment, but this was not
      significant. Older age and the presence of a CVC were associated with an
      increased risk of death in the first year of treatment. CONCLUSION: The HS
      Programme made no difference to mortality in the first year of chronic dialysis.
      Early survival for both HS and non-HS groups was excellent when compared to
      international data. Increasing age and the presence of a CVC at the start of
      chronic dialysis were the two factors that impacted significantly on 1-year
      survival.

PMID- 25985841
TI  - Fetal MRI demonstrating vein of Galen malformations in two successive pregnancies
      -a previously unreported occurrence.
AB  - PURPOSE: Vein of Galen malformations are rare and are usually detected in utero
      using ultrasonography. No definite genetic predisposition has been described in
      the literature. We present a case with two successive pregnancies complicated by
      vein of Galen malformations, which were assessed using fetal MRI. The putative
      role of genetic mutations is also discussed. METHODS: A 30-year-old primigravida
      presented in the third trimester with a fetus diagnosed with vein of Galen
      malformation on sonography. MRI and MR angiography were performed for further
      assessment. The subsequent pregnancy was again complicated by vein of Galen
      malformation. In addition to MRI, genetic analysis was carried out on both
      fetuses and on the parents. RESULTS: MR angiography revealed that both fetuses
      suffered from the choroidal sub-type of vein of Galen malformation, with multiple
      arterial feeders fistulating onto a midline venous pouch. The visualised anatomy
      obtained was far superior than on sonography and allowed categorisation of vein
      of Galen malformation sub-type. Genetic analysis on the mother and both fetuses
      showed variant RASA1 gene mutation. CONCLUSIONS: This case demonstrates that
      fetal MRI is a powerful tool in the investigation of in utero neurovascular
      malformations. A genetic mutation was identified, but this was of uncertain
      significance.

PMID- 25985842
TI  - Orthodoxy, recalcitrance and in-between: describing variation in seed storage
      characteristics using threshold responses to water loss.
AB  - MAIN CONCLUSION: Discrete categories of seed physiology can be explained through
      a unified concept of the structural and molecular mobility responses within cells
      to drying. Tolerance of desiccation is typically described by a threshold or low
      water content limit to survival. This convention provides fairly good distinction
      between orthodox and recalcitrant seeds, which show thresholds of less than about
      0.07 and greater than about 0.2 g H2O g DW(-1), respectively. Threshold water
      contents, however, are not direct measures of the intensity of water stress
      tolerated by seeds, nor are they measures of cell response to water stress. More
      direct criteria, that accommodate both spatial and temporal effects of water
      loss, are required to explain variation of desiccation tolerance and longevity in
      seeds from diverse genetic backgrounds and growth conditions. This essay presents
      the argument that changes in cellular volume directly quantify primary responses
      to desiccating stress in a context that also links damage, as cellular
      constituents compress, and protection, as compressed molecules form stabilizing
      structure. During desiccation, fluid cytoplasm solidifies, and the newly formed
      spatial relationships among molecules determine whether and how long viability is
      maintained. The diversity of seed behaviors suggests complexity and opportunity
      to discover molecules and mechanisms that regulate survival and perception of
      time in cells that lack metabolic function.

PMID- 25985843
TI  - A fallacious jar? The peculiar relation between descriptive premises and
      normative conclusions in neuroethics.
AB  - Ethical questions have traditionally been approached through conceptual analysis.
      Inspired by the rapid advance of modern brain imaging techniques, however, some
      ethical questions appear in a new light. For example, hotly debated trolley
      dilemmas have recently been studied by psychologists and neuroscientists alike,
      arguing that their findings can support or debunk moral intuitions that underlie
      those dilemmas. Resulting from the wedding of philosophy and neuroscience,
      neuroethics has emerged as a novel interdisciplinary field that aims at drawing
      conclusive relationships between neuroscientific observations and normative
      ethics. A major goal of neuroethics is to derive normative ethical conclusions
      from the investigation of neural and psychological mechanisms underlying ethical
      theories, as well as moral judgments and intuitions. The focus of this article is
      to shed light on the structure and functioning of neuroethical arguments of this
      sort, and to reveal particular methodological challenges that lie concealed
      therein. We discuss the methodological problem of how one can--or, as the case
      may be, cannot--validly infer normative conclusions from neuroscientific
      observations. Moreover, we raise the issue of how preexisting normative ethical
      convictions threaten to invalidate the interpretation of neuroscientific data,
      and thus arrive at question-begging conclusions. Nonetheless, this is not to deny
      that current neuroethics rightly presumes that moral considerations about actual
      human lives demand empirically substantiated answers. Therefore, in conclusion,
      we offer some preliminary reflections on how the discussed methodological
      challenges can be met.

PMID- 25985844
TI  - 10 Years Later: Changes in Food Access Disparities in New Orleans since Hurricane
      Katrina.
AB  - Inadequate access to healthy food is a problem in many urban neighborhoods,
      particularly for racial-ethnic minorities and low-income groups who are more
      likely to reside in food deserts. Although substantial research throughout the
      country has documented the existence of these disparities, few studies have
      focused on how this access changes over time or is affected by environmental
      shocks. This study examined citywide supermarket access in New Orleans as well as
      racial-ethnic disparities in this access, prior to Hurricane Katrina and at three
      times afterwards. On-the-ground verification of supermarket locations was
      conducted in 2004-2005, 2007, 2009, and 2014 and was mapped with secondary
      demographic data. Census tracts were defined as predominantly African-American
      neighborhoods if 80 % or more of the population identified as such. HLM Poisson
      regression analyses were conducted in 2014 to identify the difference in
      likelihood of finding supermarkets in a neighborhood by race-ethnicity and across
      all years of interest. Racial-ethnic disparities existed before the storm and
      worsened after it (IRR = 0.35; 95 % CI = 0.21, 0.60). Improvements in disparities
      to pre-storm levels were not seen until 2009, 4 years after the storm. By 2014,
      supermarket access, on average, was not significantly different in African
      American neighborhoods than in others (IRR = 0.90; 95 % CI = 0.65, 1.26). The
      slow recovery of New Orleans' retail food infrastructure after Hurricane Katrina
      highlights the need for an increased focus on long-term planning to address
      disparities, especially those that may be exaggerated by shocks. 

PMID- 25985845
TI  - Replacing a double-lumen tube with a single-lumen tube or a laryngeal mask airway
      device to reduce coughing at emergence after thoracic surgery: a randomized
      controlled single-blind trial.
AB  - BACKGROUND: Coughing episodes occur frequently at extubation after thoracic
      surgery, and this may be due in part to the double-lumen tube (DLT). In this
      study, the DLT was replaced with either a single-lumen endotracheal tube (ETT) or
      a laryngeal mask airway (LMA) device or left in place, and the incidence of
      coughing at emergence was compared between the three groups. METHODS: Fifty-eight
      adults scheduled for thoracic surgery with a DLT were included. Exclusion
      criteria were an anticipated difficult airway, obesity, and contraindication to
      the use of an LMA ProSealTM (LMA-P). After surgery but before emergence, patients
      were randomized to having the DLT (1) removed and replaced by an LMA-P (LMA-P
      Group), (2) removed and replaced by an ETT (ETT Group), or (3) left in place (DLT
      Group). The primary outcome was the number of coughing episodes at extubation.
      RESULTS: Among 184 patients screened, 124 did not meet inclusion criteria, and
      two patients, both in the ETT Group, were excluded after randomization, leaving
      20, 18, and 20 patients in the LMA-P, ETT, and DLT Groups, respectively. There
      were fewer coughing episodes (median [quartiles]) in the LMA-P Group than in the
      DLT Group (0[0-1] vs 2[1-3], respectively; P = 0.01). In the DLT Group, 90% of
      patients coughed at least once. This incidence was not significantly different in
      the ETT Group (83%; P = 0.222) but was significantly reduced in the LMA-P Group
      (35%; P < 0.001). No patient had oxygen desaturation during airway exchange or at
      extubation. The incidence and severity of hoarseness and sore throat were similar
      in all groups. CONCLUSION: Coughing at extubation after thoracic surgery can be
      reduced if the DLT is replaced by an LMA-P before emergence. The number of
      patients in this trial was too small to evaluate the risks associated with
      exchanging the airway device. This trial was registered at ClinicalTrials.gov:
      NCT00925613.

PMID- 25985847
TI  - Patterns of movement behaviors and their association with overweight and obesity
      in youth.
AB  - OBJECTIVES: To identify underlying subgroups based on patterns of physical
      activity, screen-based sedentary behavior, and sleep in a large sample of
      Canadian youth and to examine the associations between the identified subgroups
      and overweight and obesity. METHODS: The study is based on 19,831 youth aged 13
      18 years from across Ontario, Canada in the COMPASS study. Participants self
      reported their movement behaviors (i.e., physical activity, sedentary behavior
      and sleep), height and weight, and demographics. Latent class analysis and
      logistic regression models were conducted. RESULTS: Three underlying subgroups
      were identified in the total sample and male and female subsamples (i.e.,
      unhealthiest movers, active screenies, healthiest movers). In the total sample,
      the active screenies subgroup was 1.19 (95 % CI 1.09-1.29) times and the
      unhealthiest movers subgroup was 1.24 (1.14-1.36) times more likely to be
      classified as overweight/obese compared to the healthiest movers subgroup.
      Similar associations were observed in the female subsample but not in the male
      subsample. CONCLUSIONS: Public health interventions targeting youth subgroups at
      increased risk of overweight and obesity through integrated approaches accounting
      for multiple movement behaviors should be considered, especially for females.

PMID- 25985846
TI  - Using human induced pluripotent stem cells to model cerebellar disease: hope and
      hype.
AB  - The cerebellum forms a highly ordered and indispensible component of motor
      function within the adult neuraxis, consisting of several distinct cellular
      subtypes. Cerebellar disease, through a variety of genetic and acquired causes,
      results in the loss of function of defined subclasses of neurons, and remains a
      significant and untreatable health care burden. The scarcity of therapies in this
      arena can partially be explained by unresolved disease mechanisms due to
      inaccessibility of human cerebellar neurons in a relevant experimental context
      where initiating disease mechanisms could be functionally elucidated, or drug
      screens conducted. In this review we discuss the potential promise of human
      induced pluripotent stem cells (hiPSCs) for regenerative neurology, with a
      particular emphasis on in vitro modelling of cerebellar degeneration. We discuss
      progress made thus far using hiPSC-based models of neurodegeneration, noting the
      relatively slower pace of discovery made in modelling cerebellar dysfunction. We
      conclude by speculating how strategies attempting cerebellar differentiation from
      hiPSCs can be refined to allow the generation of accurate disease models. This in
      turn will permit a greater understanding of cerebellar pathophysiology to inform
      mechanistically rationalised therapies, which are desperately needed in this
      field. 

PMID- 25985848
TI  - Renoprotective Effect of Humic Acid on Renal Ischemia-Reperfusion Injury: An
      Experimental Study in Rats.
AB  - Humic acid is an antioxidant molecule used in agriculture and livestock breeding,
      as well as in medicine. Our aim was to investigate the potential renoprotective
      effects of humic acid in a renal ischemia reperfusion model. Twenty-one rats were
      randomly divided into three equal groups. Intraperitoneal serum or humic acid was
      injected at 1, 12, and 24 h. Non-ischemic group I was evaluated as sham. The left
      renal artery was clamped in serum (group II) and intraperitoneal humic acid
      (group III) to subject to left renal ischemic reperfusion procedure. Ischemia and
      reperfusion time was 60 min for each. Total antioxidant status, total oxidative
      status, oxidative stress index, and ischemia-modified albumin levels were
      analyzed biochemically from the serum samples. Kidneys were evaluated
      histopatologically and immunohistochemically. Biochemical results showed that
      total oxidative status, ischemia-modified albumin, and oxidative stress index
      levels were significantly decreased, but total antioxidant status was increased
      in the humic acid group (III) compared with the ischemia group (II) On
      histopathological examination, renal tubular dilatation, tubular cell damage and
      necrosis, dilatation of Bowman's capsule, hyaline casts, and tubular cell
      spillage were decreased in the humic acid group (III) compared with the ischemia
      group (II). Immunohistochemical results showed that apoptosis was deteriorated in
      group III. Renal ischemia reperfusion injury was attenuated by humic acid
      administration. These observations indicate that humic acid may have a potential
      therapeutic effect on renal ischemia reperfusion injury by preventing oxidative
      stress. 

PMID- 25985849
TI  - Acetoclastic methanogenesis is likely the dominant biochemical pathway of
      palmitate degradation in the presence of sulfate.
AB  - Long chain fatty acids (LCFAs) are important intermediates in the anaerobic
      degradation of n-alkanes. In order to find out the biochemical processes involved
      in the degradation of LCFAs, palmitate (a typical LCFA) was used as a substrate,
      and low-temperature oilfield production fluids were used as a source of
      microorganisms to establish two anaerobic systems, one with addition of sulfate
      as exogenous electron acceptor (SP), another without exogenous electron acceptor
      (MP) and both incubated at room temperature. After more than 2 years of
      incubation, about 48 and 57.4% of the palmitate were degraded in samples of MP
      and SP, respectively. Methane production reached 1408 and 1064 MUmol for MP and
      SP, respectively. Clone libraries of archaeal 16S rRNA genes showed that the
      predominant archaea in the sulfate-amended cultures (SP) was Methanosaeta whereas
      Methanocalculus dominated the culture without addition of exogenous sulfate (MP).
      This observation shows that palmitate could be biodegraded into methane through
      beta-oxidation and acetoclastic methanogenesis in the presence of with or without
      sulfate. The high occurrence of Methanosaeta in the sulfate-amended system
      indicates that acetoclastic methanogenesis was not inhibited/little affected by
      the addition of sulfate. Acetoclastic methanogenesis might be the predominant
      biochemchimcal pathway of methane generation in enrichment cultures amended with
      sulfate. These results shed light on alternative methanogenic pathways in the
      presence of sulfate.

PMID- 25985850
TI  - Development of a conceptual model evaluating the humanistic and economic burden
      of Crohn's disease: implications for patient-reported outcomes measurement and
      economic evaluation.
AB  - The primary objective of this review is to develop a conceptual model for Crohn's
      disease (CD) outlining the disease burden for patients, healthcare systems and
      wider society, as reported in the scientific literature. A search was conducted
      using MEDLINE, PsycINFO, EconLit, Health Economic Evaluation Database and Centre
      for Reviews and Dissemination databases. Patient-reported outcome (PRO) measures
      widely used in CD were reviewed according to the US FDA PRO Guidance for
      Industry. The resulting conceptual model highlights the characterization of CD by
      gastrointestinal disturbances, extra-intestinal and systemic symptoms. These
      symptoms impact physical functioning, ability to complete daily activities,
      emotional wellbeing, social functioning, sexual functioning and ability to work.
      Gaps in conceptual coverage and evidence of reliability and validity for some PRO
      measures were noted. Review findings also highlight the substantial direct and
      indirect costs associated with CD. Evidence from the literature confirms the
      substantial burden of CD to patients and wider society; however, future research
      is still needed to further understand burden from the perspective of patients and
      to accurately understand the economic burden of disease. Challenges with existing
      PRO measures also suggest the need for future research to refine or develop new
      measures. 

PMID- 25985853
TI  - Plasmon-enhanced homogeneous and heterogeneous triplet-triplet annihilation by
      gold nanoparticles.
AB  - We report the investigation of surface plasmon induced enhancement of homogeneous
      and heterogeneous triplet-triplet annihilation (TTA) by gold nanoparticles
      (AuNPs). Results show that AuNPs enhance the overall efficiency in both cases.
      Excitation rate and intersystem crossing efficiency of the sensitizer, and
      efficiency of energy transfer between sensitizer and acceptor are believed to be
      enhanced by the surface plasmon of AuNPs, leading to the enhancement of overall
      TTA efficiency. 

PMID- 25985852
TI  - BAG2 Is Repressed by NF-kappaB Signaling, and Its Overexpression Is Sufficient to
      Shift Abeta1-42 from Neurotrophic to Neurotoxic in Undifferentiated SH-SY5Y
      Neuroblastoma.
AB  - Amyloid-beta (Abeta) binds to various neuronal receptors and elicits a context-
      and dose-dependent toxic or trophic response from neurons. The molecular
      mechanisms for this phenomenon are presently unknown. The cochaperone BAG2 has
      been shown to mediate important cellular responses to stress, including cell
      cycle arrest and apoptosis. Here, we use SH-SY5Y neuroblastoma cells to
      characterize BAG2 expression and regulation and investigate the involvement of
      BAG2 in Abeta1-42-mediated neurotrophism or neurotoxicity in the context of
      differentiation. We report that BAG2 is upregulated on differentiation of SH-SY5Y
      cells into neuron-like cells. This increase in BAG2 expression is accompanied by
      a change in response to treatment with Abeta1-42 from neurotrophic to neurotoxic.
      Further, overexpression of BAG2 in undifferentiated SH-SY5Y cells was sufficient
      to induce the change from neurotrophic to neurotoxic response. Of several
      transcription factors queried, the putative BAG2 promoter had a higher-than
      expected occurrence of response elements (RE) for nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB). Treatment with JSH-23, a potent
      inhibitor of NF-kappaB, caused a marked increase in BAG2 mRNA expression,
      suggesting that NF-kappaB is a repressor of BAG2 transcription in
      undifferentiated SH-SY5Y cells. Together, these data suggest that NF-kappaB
      mediated modulation of BAG2 expression constitutes a "switch" that regulates the
      shift between the neurotrophic and neurotoxic effects of Abeta1-42. 

PMID- 25985851
TI  - The Effect of Vitamin A Supplementation on FoxP3 and TGF-beta Gene Expression in
      Avonex-Treated Multiple Sclerosis Patients.
AB  - Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous
      system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is
      involved in disease immunopathogenesis. The vitamin A active metabolite, retinoic
      acid, can re-establish this imbalance through the modulation of gene expression
      of specific nuclear receptors including Forkhead box P3 (FoxP3). At present, few
      data exist on the impact of vitamin A supplementation on T cell balance. This
      study reports the results of a clinical trial, over a 6-month period, of 36
      relapsing-remitting MS (RRMS) patients that received vitamin A (25,000 IU retinyl
      palmitate) or placebo (one capsule of placebo per day). Peripheral blood
      mononuclear cells were isolated from patients, and the expression of FoxP3 and
      transforming growth factor (TGF)-beta gene expression was measured using real
      time PCR at the beginning and end of the study. The results of this study showed
      that vitamin A upregulated TGF-beta and FoxP3 gene expression. Therefore, vitamin
      A supplementation can be considered as a new approach in MS prevention and
      treatment.

PMID- 25985855
TI  - A general solid-state synthesis of chemically-doped fluorescent graphene quantum
      dots for bioimaging and optoelectronic applications.
AB  - Graphene quantum dots (GQDs) have attracted increasing interest because of their
      excellent properties such as strong photoluminescence, excellent biocompatibility
      and low cost. Herein, we develop a general method for the synthesis of doped and
      undoped GQDs, which relies on direct carbonization of organic precursors in the
      solid state. 

PMID- 25985854
TI  - Kinetics of nickel bioaccumulation and its relevance to selected cellular
      processes in leaves of Elodea canadensis during short-term exposure.
AB  - Elodea canadensis is an aquatic macrophyte used widely as a bioindicator for the
      monitoring of water quality and in the phytoremediation of metal-contaminated
      waters. This study considers the kinetics of nickel bioaccumulation and changes
      in accompanying metabolic and stress-related physiological parameters. These
      include photosynthetic activity, pigment content, the accumulation of thiol
      containing compounds, thiobarbituric acid-reactive substance (TBARS) products,
      and the activity of selected antioxidant enzymes (catalase, glutathione
      reductase, superoxide dismutase). Elodea leaves accumulated nickel according to
      pseudo-second-order kinetics, and the protective responses followed a time
      sequence which was related to the apparent rates of nickel accumulation. The
      applicability of second-order kinetics to the Ni uptake by Elodea leaves during
      the first 8 h of exposure to the metal suggested that the passive binding of
      metal ions (chemisorption) was a rate-limiting step at the initial phase of Ni
      accumulation. This phase was accompanied by an increase in photosynthetic
      activity together with elevated photosynthetic pigments and protein synthesis,
      the enhanced activity of antioxidant enzymes, and increased thiol concentration.
      In contrast, there was a decrease in metabolic activity upon the accumulation of
      TBARS, and the decline in enzyme activity was observed in the saturation phase of
      Ni accumulation (8-24 h). These results show that a correlation exists between
      the protective response and the apparent kinetic rate of Ni uptake. Thus, the
      time of exposure to the toxicant is a crucial factor in the activation of
      specific mechanisms of Ni detoxification and stress alleviation.

PMID- 25985856
TI  - Indocyanine Green-Encapsulated Hybrid Polymeric Nanomicelles for Photothermal
      Cancer Therapy.
AB  - Indocyanine green (ICG), an FDA approved medical near-infrared (NIR) imaging
      agent, has been extensively used in cancer theranosis. However, the limited
      aqueous photostability, rapid body clearance, and poor cellular uptake severely
      restrict its practical applications. For these problems to be overcome, ICG
      encapsulated hybrid polymeric nanomicelles (PNMs) were developed in this work
      through coassociation of the amphiphilic diblock copolymer poly(lactic-co
      glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and hydrophobic electrostatic
      complexes composed of ICG molecules and branched poly(ethylenimine) (PEI). The
      ICG-encapsulated hybrid PNMs featured a hydrophobic PLGA/ICG/PEI core stabilized
      by hydrophilic PEG shells. The encapsulation of electrostatic ICG/PEI complexes
      into the compact PLGA-rich core not only facilitated the ICG loading but also
      promoted its aqueous optical stability. The effects of the chain length of PEI in
      combination with ICG on the physiochemical properties of PNMs and their drug
      leakage were also investigated. PEI(10k) (10 kDa) could form highly robust and
      dense complexes with ICG, and thus prominently reduced ICG outflow from the PNMs.
      The results of in vitro cellular uptake and cytotoxicity studies revealed that
      the ICG/PEI(10k)-loaded PNMs significantly promoted cellular uptake of ICG by
      HeLa cells due to their near-neutral surface, and thereby augmented the NIR
      triggered hyperthermia effect in destroying cancer cells. These findings strongly
      indicate that the ICG/PEI10k-loaded PNMs have significant potential for attaining
      effective cancer imaging and photothermal therapy.

PMID- 25985858
TI  - Neurofeedback training improves the dual-task performance ability in stroke
      patients.
AB  - Owing to the reduced capacity for information processing following a stroke,
      patients commonly present with difficulties in performing activities of daily
      living that combine two or more tasks. To address this problem, in the present
      study, we investigated the effects of neurofeedback training on the abilities of
      stroke patients to perform dual motor tasks. We randomly assigned 20 patients who
      had sustained a stroke within the preceding 6 months to either a pseudo
      neurofeedback (n = 10) or neurofeedback (n = 10) group. Both groups participated
      in a general exercise intervention for 8 weeks, three times a week for 30 min per
      session, under the same conditions. An electrode was secured to the scalp over
      the region of the central lobe (Cz), in compliance with the International 10-20
      System. The electrode was inactive for the pseudo-training group. Participants in
      the neurofeedback training group received the 30-min neurofeedback training per
      session for reinforcing the sensorimotor rhythm. Electroencephalographic activity
      of the two groups was compared. In addition, selected parameters of gait
      (velocity, cadence [step/min], stance phase [%], and foot pressure) were analyzed
      using a 10-m walk test, attention-demanding task, walk task and quantified by the
      SmartStep system. The neurofeedback group showed significantly improved the
      regulation of the sensorimotor rhythm (p < 0.001) and ability to execute dual
      tasks (p < 0.01). Significant improvements on selected gait parameters (velocity
      and cadence; p < 0.05) were also observed. We thus propose that the neurofeedback
      training is effective to improve the dual-task performance in stroke patients. 

PMID- 25985857
TI  - Hypoglycemic, hypolipidemic and antioxidant effects of peptides from red deer
      antlers in streptozotocin-induced diabetic mice.
AB  - Diabetes mellitus is a serious chronic metabolic disorder. To develop novel anti
      diabetic drugs from nature sources has always been the focus of research. Red
      deer (Cervus elaphu Linnaeus) antler is one of the most famous Chinese
      traditional medicines. We found that the peptides of 5-10 kDa from red deer
      antlers (PRDA) promoted the growth of cultured rat islet cells. The purpose of
      this study was to investigate the anti-diabetic actions of PRDA in vivo and
      purify a pure active peptide. We therefore investigated the hypoglycemic,
      hypolipidemic and antioxidant effects of PRDA in streptozotocin-induced diabetic
      mice and isolated a pure anti-diabetic peptide. PRDA, given intraperitoneally
      (75, 150, or 300 MUg/kg), significantly decreased the blood glucose levels,
      significantly increased the insulin concentrations, and remarkably improved the
      lipid metabolism in the diabetic mice. PRDA significantly increased the
      superoxide dismutase activity, catalase activity and the total antioxidant
      capacity in the serum and liver, and simultaneously decreased the malondialdehyde
      levels. The activities of hexokinase and pyruvate kinase, two important enzymes
      involved in glucose utilization, were also significantly increased in the liver
      of the PRDA-treated diabetic mice. Moreover, a novel anti-diabetic peptide
      isolated from PRDA significantly promoted the viability of cultured rat
      insulinoma cells. The molecular mass of the purified peptide was 7064.8 Da under
      mass spectrometry, and its N-terminal amino acid sequence was identified as
      LSPFTTKTYFPHFDLSHGSA. Thus, PRDA may be useful in managing the hyperglycemia,
      hyperlipidemia, and oxidative stress in diabetes, and the anti-diabetic peptide
      is a promising drug for the treatment of diabetes. 

PMID- 25985859
TI  - Review of small synthetic molecules targeting HBV capsid assembly.
AB  - Currently, the treatment for HBV infection suffers from adverse side effects and
      drug resistance. The dramatic development of new HBV inhibitors is focused on
      discovering diverse non-nucleoside compounds with either novel structures or new
      mechanisms of action. Capsid assembly is crucial to the completion of the viral
      life cycle, which makes it an attractive target for antivirus discovery.
      Inhibitors that block the formation of the HBV capsid have been developed, and
      several candidates have been proposed. In this review, we focus on the recent
      advances in several distinct classes of synthetic small molecular non-nucleosides
      targeting at the capsid assembly. 

PMID- 25985860
TI  - Design, synthesis and QSAR studies on a series of 2, 5-disubstituted- 1,3,4
      oxadiazole derivatives of diclofenac and naproxen for analgesic and anti
      inflammatory activity.
AB  - A series of twenty molecules belonging to 2,5-disubstituted-1,3,4-oxadiazole
      derivatives of Diclofenac and Naproxen were designed, synthesized and their
      structures were confirmed by spectroscopy. The target compounds were evaluated
      for anti-inflammatory and analgesic activity. The result indicates that the
      compounds 12, 4, 6, 7 and 15 were found to have good analgesic and anti
      inflammatory activities, while the compounds 12 and 14 were found to have good
      analgesic and the compound 22 were found to have good anti-inflammatory
      activities. HQSAR and Topomer QSAR studies were performed to get insights in the
      structures contributing for biological activity. The compounds bearing mono
      substitution such as Cl, OCH3 and NO2 in the phenyl ring were found to have
      maximum analgesic and anti-inflammatory activities. 

PMID- 25985861
TI  - New N,N,N',N'-tetradentate Pyrazoly Agents: Synthesis and Evaluation of their
      Antifungal and Antibacterial Activities.
AB  - A new library of N,N,N',N' -tetradentate pyrazoly compounds containing a pyrazole
      moiety was synthesized by the condensation of (3,5-dimethyl-1H-pyrazol-1
      yl)methanol 2a or (1H-pyrazol-1-yl)methanol 2b with a series of primary diamines
      in refluxed acetonitrile for 6h. The antifungal activity against the budding
      yeast Saccharomyces cerevisiae, as well as the antibacterial activity against
      Escherichia coli of these new tetradentate ligands were studied. We found that
      these tetradentate ligands act specifically as antifungal agents and lack
      antibacterial activity. Their biological activities depend on the nature of the
      structure of the compounds. 

PMID- 25985862
TI  - Tartaric Acid Enhances Adrenergic Receptor Activity: Test of a General Theory of
      Extracellular Aminergic GPCR Enhancer Discovery.
AB  - Several different classes of compounds enhance the potency of aminergic receptor
      ligands three-fold or more and increase their duration of activity up to ten
      fold. These enhancers include the vitamins ascorbic acid and folic acid,
      chelators such as ethylenediaminetetraacetic acid, corticosteroids, and opioids,
      opiates and opiate antagonists. We have previously demonstrated that all of these
      classes of enhancers share a common molecular motif consisting of a linear array
      of two hydroxyls and a carbonyl. We demonstrate here that because of this common
      molecular motif, all compounds known to enhance aminergic receptor ligands bind
      to highly conserved regions of the first or second extracellular loops of
      aminergic receptors at physiologically or pharmacologically relevant
      concentrations. These compounds also bind directly to aminergic ligands with
      significant specificity and affinity. These results suggest three very simple,
      complementary methods for screening for novel extracellular aminergic receptor
      enhancers: 1) in silico screening for the presence of the common aminergic
      receptor enhancer motif; 2) screening for binding to the aminergic ligand of
      choice; and 3) screening for binding to receptor peptides representing the
      enhancer binding site on the receptor. Using these three complementary methods,
      we predict a new class of enhancers (tartaric acids) and demonstrate the
      predicted enhancement in an in vitro smooth muscle assay. 

PMID- 25985863
TI  - Analyzing Carbohydrate-Protein Interaction Based on Single Plasmonic Nanoparticle
      by Conventional Dark Field Microscopy.
AB  - We demonstrated a practical method to analyze carbohydrate-protein interaction
      based on single plasmonic nanoparticles by conventional dark field microscopy
      (DFM). Protein concanavalin A (ConA) was modified on large sized gold
      nanoparticles (AuNPs), and dextran was conjugated on small sized AuNPs. As the
      interaction between ConA and dextran resulted in two kinds of gold nanoparticles
      coupled together, which caused coupling of plasmonic oscillations, apparent color
      changes (from green to yellow) of the single AuNPs were observed through DFM.
      Then, the color information was instantly transformed into a statistic peak
      wavelength distribution in less than 1 min by a self-developed statistical
      program (nanoparticleAnalysis). In addition, the interaction between ConA and
      dextran was proved with biospecific recognition. This approach is high-throughput
      and real-time, and is a convenient method to analyze carbohydrate-protein
      interaction at the single nanoparticle level efficiently. 

PMID- 25985864
TI  - Liraglutide: a review of its use in the management of obesity.
AB  - Globally, obesity has reached epidemic proportions and poses an ever increasing
      burden from a societal and healthpayer perspective. Although lifestyle
      interventions are fundamental in its management, in the real world setting most
      obese or overweight adults require adjunctive pharmacotherapy to achieve
      clinically relevant reductions in bodyweight (i.e. a >=5 % reduction).
      Subcutaneous liraglutide (Saxenda((r))) 3 mg once daily is indicated as an
      adjunct to a reduced-calorie diet and increased physical activity for chronic
      bodyweight management in adults with an initial body mass index (BMI) of >=30
      kg/m(2) (obese) or a BMI of >=27 kg/m(2) (overweight) and at least one bodyweight
      related comorbidity [e.g. hypertension, dyslipidaemia, type 2 diabetes mellitus
      or obstructive sleep apnoea (OSA)]. In phase III trials (32 or 56 weeks'
      duration) in these populations, subcutaneous liraglutide was associated with
      clinically relevant reductions in fasting bodyweight and was generally well
      tolerated. Liraglutide was significantly more effective than placebo in terms of
      reductions in fasting bodyweight and waist circumference, and improvements in
      some biomarkers of cardiovascular risk. Improvements in bodyweight were
      maintained after up 2 years of liraglutide therapy. In nondiabetic adults with
      moderate to severe OSA, liraglutide improved apnoea-hypopnoea index scores at 32
      weeks, which was largely driven by significant reductions in bodyweight. In the
      absence of head-to-head trials, the relative position of individual anti-obesity
      drugs remains to be fully determined. In the meantime, liraglutide is an emerging
      option, as an adjunct to a reduced-calorie diet and increased physical activity,
      for chronic bodyweight management in obese adults and overweight adults with at
      least one bodyweight-related comorbidity.

PMID- 25985866
TI  - Arrhythmias: Atrial fibrillation increases risk of NSTEMI.

PMID- 25985867
TI  - Pulmonary embolism: No clinical benefit of vena cava filter in patients who can
      be anticoagulated.

PMID- 25985868
TI  - Prehypertension-new insights for health risks.

PMID- 25985865
TI  - The New Era of Drug Therapy for Obesity: The Evidence and the Expectations.
AB  - There is an urgent need for effective pharmacological therapies to help tackle
      the growing obesity epidemic and the healthcare crisis it poses. The past 3 years
      have seen approval of a number of novel anti-obesity drugs. The majority of these
      influence hypothalamic appetite pathways via dopaminergic or serotoninergic
      signalling. Some are combination therapies, allowing lower doses to minimize the
      potential for off-target effects. An alternative approach is to mimic endogenous
      satiety signals using long-lasting forms of peripheral appetite-suppressing
      hormones. There is also considerable interest in targeting thermogenesis by brown
      adipose tissue to increase resting energy expenditure. Obesity pharmacotherapy
      has seen several false dawns, but improved understanding of the pathways
      regulating energy balance, and better-designed trials, give many greater
      confidence that recently approved agents will be both efficacious and safe.
      Nevertheless, a number of issues from preclinical and clinical development
      continue to attract debate, and additional large-scale trials are still required
      to address areas of uncertainty. 

PMID- 25985869
TI  - Heart failure: Mesenchymal stromal cell therapy improves myocardial function
      after severe ischaemic heart failure.

PMID- 25985871
TI  - Impact of Long-Term Irrigation with Treated Sewage on Soil Magnetic
      Susceptibility and Organic Matter Content in North China.
AB  - This study assessed the effect on magnetic susceptibility and organic matter
      content of arable soil by irrigation with either treated sewage or groundwater.
      Results indicated that organic matter and magnetic susceptibility values in the
      soil irrigated with sewage were increased by 7.1 % and 13.5 %, respectively,
      compared to agricultural soil that irrigated with groundwater. Both the sewage
      and groundwater irrigated soils contained a significant fraction of ultrafine
      superpara magnetic grains, as indicated by high frequency dependent
      susceptibility (chifd > 6 %). The enhancement of soil magnetic properties was
      determined to be caused by anthropogenic sewage irrigation and agrochemical use
      by investigation of vertical soil profiles. Magnetic susceptibility parameters
      were shown to be significantly correlated with organic matter content (y =
      0.0057x + 1.3439, R(2) = 0.09, p < 0.05). This work indicates that measurements
      of magnetic susceptibility may offer a rapid first step for identifying the
      potential pollution in arable soils.

PMID- 25985870
TI  - Propofol administration in patients with methylmalonic acidemia and intracellular
      cobalamin metabolism disorders: a review of theoretical concerns and clinical
      experiences in 28 patients.
AB  - BACKGROUND: Methylmalonic acidemia and intracellular cobalamin metabolism
      disorders represent a heterogeneous group of inborn errors of metabolism. Most
      patients will require diagnostic and/or therapeutic procedures frequently
      requiring sedation or anesthetic management due to neurological and
      neurocognitive impairments. It has been stated that propofol is contraindicated
      in this population. We report our experience with propofol administration in a
      large series of patients. METHODS: Twenty eight patients (14 mut, seven cblC,
      three cblA, three cblB, one cblG) aged 2-35.6 years enrolled in a natural history
      study (ClinicalTrials.gov identifier: NCT00078078) and required anesthetics for
      39 diagnostic or therapeutic procedures. Data were collected on the anesthetic
      technique, perianesthetic course, and adverse events related to propofol.
      RESULTS: Propofol was used as the sole induction agent in most cases (36/39) and
      as the primary maintenance agent in all cases. Infusion rates were 100-400 mcg
      kg(-1) min(-1) (mean = 214). Infusion duration was 60-325 min (mean = 158) and
      total doses ranged between 270-3610 mg (mean = 1217). Adverse events were
      recorded in two cases; neither appeared to be related to propofol administration.
      CONCLUSIONS: Propofol is an effective, safe induction and maintenance agent for
      elective short procedures requiring anesthesia in patients with MMA and cobalamin
      metabolism disorders. Despite multiple comorbidities and propensity toward
      instability, those affected can receive anesthesia with an acceptable safety
      profile, if metabolically and hemodynamically stabilized prior to the event.
      SYNOPSIS: A review of the perianesthetic records of 28 patients with isolated MMA
      and intracellular cobalamin metabolism disorders suggests that propofol
      anesthesia can be administered safely to these patients, in the setting of
      metabolic stability.

PMID- 25985872
TI  - Measuring and Reducing Off-Target Activities of Programmable Nucleases Including
      CRISPR-Cas9.
AB  - Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription
      activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases
      (RGENs) repurposed from the type II clustered, regularly interspaced short
      palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now
      widely used for genome editing in higher eukaryotic cells and whole organisms,
      revolutionising almost every discipline in biological research, medicine, and
      biotechnology. All of these nucleases, however, induce off-target mutations at
      sites homologous in sequence with on-target sites, limiting their utility in many
      applications including gene or cell therapy. In this review, we compare methods
      for detecting nuclease off-target mutations. We also review methods for profiling
      genome-wide off-target effects and discuss how to reduce or avoid off-target
      mutations. 

PMID- 25985874
TI  - The Structural Development of the Mouse Dorsal Cochlear Nucleus.
AB  - The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian
      cochlear nucleus (CN) that is thought to be involved in sound localization in the
      vertical plane and in feature extraction of sound stimuli. The main principal
      cell type (pyramidal cells) integrates auditory and non-auditory inputs, which
      are considered to be important in performing sound localization tasks. This study
      aimed to investigate the histological development of the CD-1 mouse DCN,
      focussing on the postnatal period spanning the onset of hearing (P12).
      Fluorescent Nissl staining revealed that the three layers of the DCN were
      identifiable as early as P6 with subsequent expansion of all layers with age.
      Significant increases in the size of pyramidal and cartwheel cells were observed
      between birth and P12. Immunohistochemistry showed substantial changes in
      synaptic distribution during the first two postnatal weeks with subsequent
      maturation of the presumed mossy fibre terminals. In addition, GFAP
      immunolabelling identified several glial cell types in the DCN including the
      observation of putative tanycytes for the first time. Each glial cell type had
      specific spatial and temporal patterns of maturation with apparent rapid
      development during the first two postnatal weeks but little change thereafter.
      The rapid maturation of the structural organization and DCN components prior to
      the onset of hearing possibly reflects an influence from spontaneous activity
      originating in the cochlea/auditory nerve. Further refinement of these
      connections and development of the non-auditory connections may result from the
      arrival of acoustic input and experience dependent mechanisms. 

PMID- 25985875
TI  - HER2 gene and protein expression status of breast carcinoma can be reliably
      tested on a single slide.
AB  - Human epidermal growth factor receptor 2 (HER2) status in breast carcinomas
      serves as a predictor of benefit from anti-HER2 therapy. In providing clinicians
      with the information necessary to decide whether or not to treat with targeted
      therapy, it might be necessary to choose between methods assessing HER2 protein
      overexpression or gene amplification. A new diagnostic approach could be a
      combination of both tests on the same slide. If accurate and reproducible, this
      approach might optimize patient stratification for therapy. In this study,
      formalin-fixed paraffin-embedded tumor samples from 77 breast cancer patients
      were examined for HER2 by immunohistochemistry (IHC) and silver in situ
      hybridization (SISH) using HER2 IHC (clone 4B5), HER2/CEN17SISH, and combined IHC
      and SISH assay, called gene protein (GP). Cases were selected to ensure a
      sufficient number of borderline cases on the basis of IHC scores (0, 1+, 2+, 3+),
      obtained during diagnostic histopathological workup. The concordance between the
      HER2 IHC score obtained during diagnostic histopathological workup and GP was 93
      %. Discordances had no influence on therapy decisions. The concordance between
      ISH results using dual ISH (DISH) and GP was 96 %. Of the 77 cases studied by GP,
      three cases with a ratio close to 2 would have been called amplified by DISH. The
      use of GP reduced the time for slide reading for a trained pathologist by up to
      25 %, relative to sequential reading of IHC followed by SISH. For cases with an
      IHC score of 2+, the final result was obtained in 1 day, while the sequential
      technique would have required retesting by ISH on a second day. In conclusion,
      assessment of HER2 status by GP is an improvement for pathologists and
      facilitates clinical decision-making for breast cancer management.

PMID- 25985876
TI  - Wide-field pathology imaging using on-chip microscopy.
AB  - As the primary imaging tool to assist the examination of pathological samples,
      the conventional light microscope suffers from limited throughput, relatively
      high cost, bulky size, lack of portability, and requirement for focus adjustment.
      All of these drawbacks partially limit the use of light microscopy tools in
      resource-limited settings. Lens-free on-chip microscopy can help to address these
      drawbacks and achieve high-throughput pathology slide imaging without using
      lenses or objectives. Here, we review the performance of this lens-free imaging
      platform by showing examples of its performance with various samples including
      normal and sickle-cell disease blood smears and human carcinoma of the breast.
      This lens-free computational microscopy platform is a promising tool that can
      serve high-throughput pathology needs especially in resource-poor settings. 

PMID- 25985877
TI  - Genetic testing of leiomyoma tissue in women younger than 30 years old might
      provide an effective screening approach for the hereditary leiomyomatosis and
      renal cell cancer syndrome (HLRCC).
AB  - We have studied the viability of targeted molecular screening for the
      identification of female patients with hereditary leiomyomatosis and renal cell
      cancer (HLRCC) syndrome. Affected patients harbor a germ-line heterozygous
      mutation of the fumarate hydratase (FH) gene. Clinically, some patients present
      with aggressive renal cell carcinoma. Concerning women, in almost all cases, this
      is preceded by symptomatic uterine leiomyoma. We aimed to identify women operated
      on for symptomatic leiomyoma by the age of 30. Archived paraffin-embedded
      leiomyoma tissue was tested for the FH gene mutation in 14 cases. Two patients
      with multiple leiomyomas and with the confirmed germ-line mutations
      c.1433_1434dupAAA, p.(Lys477dup) and c.953A>T, p.(His318Leu) were identified and
      enrolled in a surveillance program. Statistically significant correlation between
      the presence of multiple uterine leiomyomas (more than seven in our experience)
      and the FH gene mutation was found. The immunohistochemical expression pattern,
      of simultaneous FH absence and S-(2-succino)cysteine (2SC) positivity, correlated
      with the results of the molecular genetic study in only one case. The
      histomorphologically simultaneous detection of enlarged nucleoli with a clear
      halo of leiomyocyte nuclei, their fibrillary cytoplasm, the presence of
      eosinophilic globules, and staghorn vessels proved to be only a partially
      sensitive indicator of HLRCC-associated leiomyoma and fully correlated with
      immunohistochemistry and molecular genetic study only in one case. Molecular
      genetic testing is presently the only reliable diagnostic tool able to identify
      HLRCC patients. The sensitivity and specificity of the presence of multiple
      leiomyomas in women with the FH gene mutation who are younger than 30 years old
      should be confirmed in larger scale studies. The applied targeted molecular
      screening protocol proved to be effective, resulting in identification of two
      positive patients out of fourteen tested individuals.

PMID- 25985879
TI  - CARS 2015-Computer Assisted Radiology and Surgery Proceedings of the 29th
      International Congress and Exhibition Barcelona, Spain, June 24-27, 2015.

PMID- 25985878
TI  - National trends in therapeutic approaches and outcomes for pediatric
      appendicitis: a Taiwanese nationwide cohort study.
AB  - PURPOSE: To define the pattern of therapeutic approaches for pediatric
      appendicitis and compare their benefits in Taiwan, we analyzed a research
      oriented dataset released by the Bureau of National Health Insurance in Taiwan
      through the Collaboration Center for Health Information Application (CCHIA) to
      document the impact of the rise of laparoscopic treatment on outcomes. METHODS:
      We identified 22,161 patients under 18 years who had been hospitalized with a
      diagnosis of acute appendicitis between 2007 and 2012 in the CCHIA. Statistical
      comparisons between the Laparoscopic appendectomy (LA) and open appendectomy (OA,
      control) groups were computed using a Chi squared test. The odds ratios (ORs) and
      95% confidence intervals (CIs) of risk factors for intra-abdominal abscess (IAA)
      and postoperative bowel obstruction (PBO) were derived from multivariate logistic
      regression models. RESULTS: In each respective year, the incidence of LA
      increased from 29.17% in 2007 to 57.4% in 2012, while that of OA decreased from
      70.83% in 2007 to 42.60% in 2012; incidences of non-perforated appendicitis and
      perforated appendicitis with LA or OA seemed similar. The length of
      hospitalization between an LA and OA for non-perforated appendicitis was the
      same, but that with an LA was shorter for perforated appendicitis. The adjusted
      ORs for IAA and PBO for those patients with perforated and non-perforated
      appendicitis were 6.30 (95% CI = 5.09-7.78; p < 0.001) and 6.49 (95% CI = 4.45
      9.48; p < 0.001); while for those cases undergoing an LA and OA, they were 0.50
      (95 % CI = 0.40-0.62; p < 0.001) and 2.07 (95% CI = 1.45-2.95; p < 0.001),
      respectively. The ORs of IAA and PBO for those patients <=6 and 7-12 years of age
      were 1.67 (95% CI = 1.23-2.25; p = 0.001) and 1.20 (95% CI = 0.97-1.49; p =
      0.095), and 1.88 (95% CI = 1.08-3.24; p = 0.025) and 1.47 (95% CI = 1.01-2.14; p
      = 0.043), respectively, compared to those aged 13-18 years. CONCLUSIONS: Our
      study demonstrated that young age and perforated appendicitis can affect
      postoperative IAA and PBO. LA appeared beneficial in reducing the length of
      hospitalization and postoperative IAA, but had an increasing risk of PBO.
      Although laparoscopic approach for pediatric appendectomy is increasing in our
      country, the different hospital levels and pediatric surgeon's laparoscopic
      experience must be evaluated in further study.

PMID- 25985880
TI  - Continuous roadmapping in liver TACE procedures using 2D-3D catheter-based
      registration.
AB  - PURPOSE: Fusion of pre/perioperative images and intra-operative images may add
      relevant information during image-guided procedures. In abdominal procedures,
      respiratory motion changes the position of organs, and thus accurate image
      guidance requires a continuous update of the spatial alignment of the
      (pre/perioperative) information with the organ position during the intervention.
      METHODS: In this paper, we propose a method to register in real time
      perioperative 3D rotational angiography images (3DRA) to intra-operative single
      plane 2D fluoroscopic images for improved guidance in TACE interventions. The
      method uses the shape of 3D vessels extracted from the 3DRA and the 2D catheter
      shape extracted from fluoroscopy. First, the appropriate 3D vessel is selected
      from the complete vascular tree using a shape similarity metric. Subsequently,
      the catheter is registered to this vessel, and the 3DRA is visualized based on
      the registration results. The method is evaluated on simulated data and clinical
      data. RESULTS: The first selected vessel, ranked with the shape similarity
      metric, is used more than 39 % in the final registration and the second more than
      21 %. The median of the closest corresponding points distance between 2D
      angiography vessels and projected 3D vessels is 4.7-5.4 mm when using the brute
      force optimizer and 5.2-6.6 mm when using the Powell optimizer. CONCLUSION: We
      present a catheter-based registration method to continuously fuse a 3DRA roadmap
      arterial tree onto 2D fluoroscopic images with an efficient shape similarity.

PMID- 25985881
TI  - Diagnostic Value of Urinary Steroid Profiling in the Evaluation of Adrenal
      Tumors.
AB  - Radiological examination may unexpectedly reveal an adrenal mass. Current
      algorithms for differentiating between benign and malignant lesions mainly rely
      on size and densitometry on unenhanced CT, which have limited specificity. We
      examined the diagnostic value of urinary steroid profiling by gas
      chromatography/mass-spectrometry (GC/MS) in differentiating between benign and
      malignant adrenal tumors. A retrospective study in two referral centers for
      patients with adrenal disease was performed. All urinary steroid profiles ordered
      for evaluation of an adrenal tumor between January 2000 and November 2011 were
      examined. Patients were diagnosed with adrenal cortical carcinoma (ACC), adrenal
      cortical adenoma (ACA), or other adrenal mass. Results of hormonal measurements,
      imaging studies, pathology reports, and clinical outcome were retrieved from
      medical records. The diagnostic value of individual urinary steroid metabolites
      was determined by receiver operating characteristics analysis. Cut-off values
      were compared to reference values from an age and gender-standardized population
      of healthy controls. Eighteen steroid metabolites were excreted in significantly
      higher concentrations in patients with ACC (n = 27) compared to patients with ACA
      (n = 107) or other adrenal conditions (n = 18). Tetrahydro-11-deoxycortisol (THS)
      at a cut-off value of 2.35 MUmol/24 h differentiated ACC from other adrenal
      disorders with 100% sensitivity and 99% specificity. Elevated urinary excretion
      of THS was associated with a very high sensitivity and specificity to
      differentiate between an ACC and a benign adrenal mass. Urinary steroid profiling
      might be a useful diagnostic test for the evaluation of patients with an adrenal
      incidentaloma.

PMID- 25985882
TI  - Impact of bone-targeted therapies in chemotherapy-naive metastatic castration
      resistant prostate cancer patients treated with abiraterone acetate: post hoc
      analysis of study COU-AA-302.
AB  - BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) often
      involves bone, and bone-targeted therapy (BTT) has become part of the overall
      treatment strategy. OBJECTIVE: Investigation of outcomes for concomitant BTT in a
      post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical
      benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone
      in asymptomatic or mildly symptomatic chemotherapy-naive mCRPC patients. DESIGN,
      SETTING, AND PARTICIPANTS: This report describes the third interim analysis
      (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.
      INTERVENTION: Patients were grouped by concomitant BTT use or no BTT use. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Radiographic progression-free survival and
      OS were coprimary end points. This report describes the third interim analysis
      (prespecified at 55% OS events) and involves patients treated with or without
      concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo.
      Median time-to-event variables with 95% confidence intervals (CIs) were estimated
      using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p
      values for concomitant BTT versus no BTT were obtained via Cox models. RESULTS
      AND LIMITATIONS: While the post hoc nature of the analysis is a limitation,
      superiority of AA and prednisone versus prednisone alone was demonstrated for
      clinical outcomes with or without BTT use. Compared with no BTT use, concomitant
      BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG
      deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain
      (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to
      that reported for AA in the overall intent-to-treat population. Osteonecrosis of
      the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.
      CONCLUSIONS: AA with concomitant BTT was safe and well tolerated in men with
      chemotherapy-naive mCRPC. The benefits of AA on clinical outcomes were increased
      with concomitant BTT. PATIENT SUMMARY: Treatment of advanced prostate cancer
      often includes bone-targeted therapy. This post hoc analysis showed that in
      patients with advanced prostate cancer who were treated with abiraterone acetate
      and prednisone in combination with bone-targeted therapy, there was a continued
      trend in prolongation of life when compared with patients treated with prednisone
      alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT00887198.

PMID- 25985883
TI  - Long-term oncologic outcomes following robot-assisted radical cystectomy: results
      from the International Robotic Cystectomy Consortium.
AB  - BACKGROUND: Long-term oncologic data on patients undergoing robot-assisted
      radical cystectomy (RARC) are limited and based largely on single-institution
      series. OBJECTIVE: Report survival outcomes of patients who underwent RARC >=5 yr
      ago. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the prospectively
      populated International Robotic Cystectomy Consortium multi-institutional
      database identified 743 patients with RARC performed >=5 yr ago. Clinical,
      pathologic, and survival data at the latest follow-up were collected. Patients
      with palliative RARC were excluded. Final analysis was performed on 702 patients
      from 11 institutions in 6 countries. INTERVENTION: RARC. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Outcomes of interest, recurrence-free survival (RFS),
      cancer-specific survival (CSS), and overall survival (OS) were plotted using
      Kaplan-Meier survival curves. A Cox proportional hazards model was used to
      identify factors that predicted outcomes. RESULTS AND LIMITATIONS: Pathologic
      organ-confined (OC) disease was found in 62% of patients. Soft tissue surgical
      margins (SMs) were positive in 8%. Median lymph node (LN) yield was 16, and 21%
      of patients had positive LNs. Median follow-up was 67 mo (interquartile range: 18
      84 mo). Five-year RFS, CSS, and OS were 67%, 75%, and 50%, respectively. Non-OC
      disease and SMs were associated with poorer RFS, CSS, and OS on multivariable
      analysis. Age predicted poorer CSS and OS. Adjuvant chemotherapy and positive SMs
      were predictors of RFS (hazard ratio: 3.20 and 2.16; p<0.001 and p<0.005,
      respectively). Stratified survival curves demonstrated poorer outcomes for
      positive SM, LN, and non-OC disease. Retrospective interrogation and lack of
      contemporaneous comparison groups that underwent open radical cystectomy were
      major limitations. CONCLUSIONS: The largest multi-institutional series to date
      reported long-term survival outcomes after RARC. PATIENT SUMMARY: Patients who
      underwent robot-assisted radical cystectomy for bladder cancer have acceptable
      long-term survival.

PMID- 25985884
TI  - Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment.
AB  - BACKGROUND: TMPRSS2:ERG (T2:ERG) and prostate cancer antigen 3 (PCA3) are the
      most advanced urine-based prostate cancer (PCa) early detection biomarkers.
      OBJECTIVE: Validate logistic regression models, termed Mi-Prostate Score (MiPS),
      that incorporate serum prostate-specific antigen (PSA; or the multivariate
      Prostate Cancer Prevention Trial risk calculator version 1.0 [PCPTrc]) and urine
      T2:ERG and PCA3 scores for predicting PCa and high-grade PCa on biopsy. DESIGN,
      SETTING, AND PARTICIPANTS: T2:ERG and PCA3 scores were generated using clinical
      grade transcription-mediated amplification assays. Pretrained MiPS models were
      applied to a validation cohort of whole urine samples prospectively collected
      after digital rectal examination from 1244 men presenting for biopsy. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Area under the curve (AUC) was used to
      compare the performance of serum PSA (or the PCPTrc) alone and MiPS models.
      Decision curve analysis (DCA) was used to assess clinical benefit. RESULTS AND
      LIMITATIONS: Among informative validation cohort samples (n=1225 [98%], 80% from
      patients presenting for initial biopsy), models incorporating T2:ERG had
      significantly greater AUC than PSA (or PCPTrc) for predicting PCa (PSA: 0.693 vs
      0.585; PCPTrc: 0.718 vs 0.639; both p<0.001) or high-grade (Gleason score >6) PCa
      on biopsy (PSA: 0.729 vs 0.651, p<0.001; PCPTrc: 0.754 vs 0.707, p=0.006). MiPS
      models incorporating T2:ERG score had significantly greater AUC (all p<0.001)
      than models incorporating only PCA3 plus PSA (or PCPTrc or high-grade cancer
      PCPTrc [PCPThg]). DCA demonstrated net benefit of the MiPS_PCPTrc (or
      MiPS_PCPThg) model compared with the PCPTrc (or PCPThg) across relevant threshold
      probabilities. CONCLUSIONS: Incorporating urine T2:ERG and PCA3 scores improves
      the performance of serum PSA (or PCPTrc) for predicting PCa and high-grade PCa on
      biopsy. PATIENT SUMMARY: Incorporation of two prostate cancer (PCa)-specific
      biomarkers (TMPRSS2:ERG and PCA3) measured in the urine improved on serum
      prostate-specific antigen (or a multivariate risk calculator) for predicting the
      presence of PCa and high-grade PCa on biopsy. A combined test, Mi-Prostate Score,
      uses models validated in this study and is clinically available to provide
      individualized risk estimates.

PMID- 25985886
TI  - 3-Year follow-up after Lasik: assessing the risk factors for retreatment.
AB  - The purpose of this study was to evaluate the correlation of important risk
      factors for LASIK retreatment and the retreatment rate. A retrospective cohort
      study was conducted. Records of patients who underwent LASIK between January 2011
      and January 2012 at the Zambrano-Hellion Medical Center, Tec de Monterrey
      (Mexico), and posteriorly underwent LASIK retreatment were identified and risk
      factors to receive retreatment were assessed using relative risk. Main outcomes
      were retreatment rate, risk factors for retreatment, and uncorrected distance
      visual acuity (UDVA). 482 eyes from 241 patients were available for a 36-month
      follow-up analysis. 68.5 % had primary myopic LASIK; 37 % were <= 2 diopters (D),
      52 % were > 2 and < 6 D, and 11 % were >= 6 D of myopia. 31.5 % of the eyes had
      hyperopic LASIK. Retreatment was performed in 6.85 % eyes. Myopia > 6 D (RR
      4.13), hyperopic refraction (RR 3.18), and age > 40 (RR 3.07) were the most
      important risk factors for retreatment (P = 0.004, P = 0.007, P = 0.006,
      respectively). UDVA was >= 20/40 in 92.1 % and >= 20/20 in 81.6 % of the
      retreated eyes and 82 % of the eyes within +/- 0.50 D of target refraction.
      Increasing degrees of myopia, followed by hyperopic refraction, and age were the
      most important associated factors to retreatment. LASIK retreatment was safe and
      effective.

PMID- 25985887
TI  - A new method for the automatic identification of the dimensional features of
      vertebrae.
AB  - In this paper a new automatic approach to determine the accurate measure of human
      vertebrae is proposed. The aim is to speed up the measurement process and to
      reduce the uncertainties that typically affect the measurement carried out by
      traditional approaches. The proposed method uses a 3D model of the vertebra
      obtained from CT-scans or 3D scanning, from which some characteristic dimensions
      are detected. For this purpose, specific rules to identify morphological
      features, from which to detect dimensional features unambiguously and accurately,
      are put forward and implemented in original software. The automatic method which
      is here proposed is verified by analysing real vertebrae and is then compared
      with the state-of-the-art methods for vertebra measurement. 

PMID- 25985885
TI  - The genetic architecture of growth and fillet traits in farmed Atlantic salmon
      (Salmo salar).
AB  - BACKGROUND: Performance and quality traits such as harvest weight, fillet weight
      and flesh color are of economic importance to the Atlantic salmon aquaculture
      industry. The genetic factors underlying these traits are of scientific and
      commercial interest. However, such traits are typically polygenic in nature, with
      the number and size of QTL likely to vary between studies and populations. The
      aim of this study was to investigate the genetic basis of several growth and
      fillet traits measured at harvest in a large farmed salmon population by using
      SNP markers. Due to the marked heterochiasmy in salmonids, an efficient two-stage
      mapping approach was applied whereby QTL were detected using a sire-based linkage
      analysis, a sparse SNP marker map and exploiting low rates of recombination,
      while a subsequent dam-based analysis focused on the significant chromosomes with
      a denser map to confirm QTL and estimate their position. RESULTS: The harvest
      traits all showed significant heritability, ranging from 0.05 for fillet yield up
      to 0.53 for the weight traits. In the sire-based analysis, 1695 offspring with
      trait records and their 20 sires were successfully genotyped for the SNPs on the
      sparse map. Chromosomes 13, 18, 19 and 20 were shown to harbor genome-wide
      significant QTL affecting several growth-related traits. The QTL on chr. 13, 18
      and 20 were detected in the dam-based analysis using 512 offspring from 10 dams
      and explained approximately 6-7 % of the within-family variation in these traits.
      CONCLUSIONS: We have detected several QTL affecting economically important
      complex traits in a commercial salmon population. Overall, the results suggest
      that the traits are relatively polygenic and that QTL tend to be pleiotropic
      (affecting the weight of several components of the harvested fish). Comparison of
      QTL regions across studies suggests that harvest trait QTL tend to be relatively
      population-specific. Therefore, the application of marker or genomic selection
      for improvement in these traits is likely to be most effective when the discovery
      population is closely related to the selection candidates (e.g. within-family
      genomic selection).

PMID- 25985888
TI  - Alterations of miR-132 are novel diagnostic biomarkers in peripheral blood of
      schizophrenia patients.
AB  - Alterations in microRNAs (miRNAs) have been considered to have diagnostic
      implications in most diseases, but few studies have reported dysregulated miRNAs
      in schizophrenia (SCZ). In order to observe an association between miRNAs and
      SCZ, this study was designed to investigate expression profiling of miRNAs in
      peripheral blood mononuclear cells (PBMCs). miRNA microarray technology was
      employed to compare the expression of miRNAs in PBMCs from SCZ patients (n=105)
      and normal controls (n=130), and real-time quantitative polymerase chain reaction
      (QPCR) was used to analyze the results. Several important miRNA levels were
      examined before and after antipsychotic treatment in first-onset SCZ patients. In
      addition, an SCZ-like rat model was established using dizocilpine (MK-801), and
      miR-132 expression in PBMCs and whole-brain tissue from SCZ-like rats was studied
      using QPCR. In humans, dysregulated miRNAs were observed before treatment and
      QPCR verified that miR-132, miR-134, miR-1271, miR-664(*), miR-200c and miR-432
      levels were significantly decreased (P<0.01 for all) in PBMCs of SCZ patients
      compared with healthy controls. After antipsychotic treatment there was a marked
      increase in miR-132 (P<0.01), miR-664(*) (P<0.05) and miR-1271 (P<0.05) levels in
      SCZ patients compared with the levels before treatment. In the animal assays, miR
      132 levels declined in PBMCs and whole-brain tissues (both P<0.05) of the SCZ
      like rats compared to controls. For the first time, our results suggest that miR
      132 is a potential and superior biomarker in peripheral blood that will allow
      discrimination of SCZ patients from healthy controls. 

PMID- 25985889
TI  - Effect of dopamine D4 receptor agonists on sleep architecture in rats.
AB  - Dopamine plays a key role in the regulation of sleep-wake states, as revealed by
      the observation that dopamine-releasing agents such as methylphenidate have wake
      promoting effects. However, the precise mechanisms for the wake-promoting effect
      produced by the enhancement of dopamine transmission are not fully understood.
      Although dopamine D1, D2, and D3 receptors are known to have differential effects
      on sleep architecture, the role of D4 receptors (D4Rs), and particularly the
      influence of D4R activation on the sleep-wake state, has not been studied so far.
      In this study, we investigated for the first time the effects of two structurally
      different D4R agonists, Ro 10-5824 and A-412997, on the sleep-wake states in
      rats. We found that both D4R agonists generally increased waking duration, and
      conversely, reduced non-rapid eye movement (NREM) sleep duration in rats. The
      onset of NREM sleep was also generally delayed. However, only the A-412997
      agonist (but not the Ro 10-5824) influenced rapid eye movement sleep onset and
      duration. Furthermore, these effects were accompanied with an enhancement of EEG
      spectral power in the theta and the gamma bands. Our results suggest the
      involvement of dopamine D4R in the regulation of sleep-wake states. The
      activation of the D4R could enhance the arousal states as revealed by the
      behavioral and electrophysiological patterns in this study. Dopamine D4R may
      contribute to the arousal effects of dopamine-releasing agents such as
      methylphenidate. 

PMID- 25985890
TI  - COPART Risk Score Predicts Long-term Mortality in Peripheral Arterial Occlusive
      Disease.
AB  - OBJECTIVES: The COhorte de Patients ARTeriopathes (COPART) Risk Score is a risk
      score assessing the 1 year outcome of patients who received inpatient treatment
      because of their peripheral arterial occlusive disease (PAOD). The COPART Risk
      Score consists of six variables each of which is allocated a different number of
      points (age, history of myocardial infarction, C-reactive protein, ankle-brachial
      index, estimated glomerular filtration rate, medication with antiplatelet agents,
      statins and renin-angiotensin system inhibitors). METHODS: 129 consecutive
      claudicants were included in a prospective trial with an average follow up of 8.8
      (+/- 0.7) years. All patients were hospitalized for their first endovascular
      procedure to the pelvic and/or femoropopliteal arteries. The endpoints were all
      cause mortality and cardiovascular (CV) death. The COPART Risk Score was
      calculated for the three patient cohorts (low risk: 52 patients [40.3%]; medium
      risk: 41 patients [31.8%]; high risk: 36 patients [27.9%]). RESULTS: During the
      follow up period 23.1% (n = 12) of patients in the low risk group, 34.1% (n = 14)
      of patients in the medium risk group, and 63.9% (n = 23) of patients in the high
      risk group died. CV death occurred in 11.5% in the low, 22.0% in the medium, and
      41.7% in the high risk groups. The three groups differed significantly with
      regard to all cause and CV mortality (p < .0001 and p = .001). CONCLUSIONS: The
      COPART Risk Score is a suitable instrument to predict long-term all cause and CV
      mortality in claudicants preceding their first peripheral intervention.

PMID- 25985891
TI  - Darwin's legacy II: why biology is not physics, or why it has taken a century to
      see the dependence of genes on the environment.
AB  - Genes and environment make the organism. Darwin stood firm in his denial of any
      direct role of environment in the modification of heredity. His theory of
      evolution heralded two debates: one about the importance and adequacy of natural
      selection as the main mechanism of evolution, and the other about the role of
      genes versus environment in the modification of phenotype and evolution. Here, I
      provide an overview of the second debate and show that the reasons for the gene
      versus environment battle were twofold: first, there was confusion about the role
      of environment in modifying the inheritance of a trait versus the evolution of
      that trait, and second, there was misunderstanding about the meaning of
      environment and its interaction with genes in the production of phenotypes. It
      took nearly a century to see that environment does not directly affect the
      inheritance of a phenotype (i.e., its heredity), but it is nevertheless the
      primary mover of phenotypic evolution. Effects of genes and environment are not
      separate but interdependent. One cannot separate the effect of genes from that of
      environment, or nature from nurture. To answer the question posed in the title,
      it is partly because the 20th century has been a century of unending progress in
      genetics. But also because unlike physics, biology is not colorblind; progress in
      biology has often been delayed beyond the Kuhnian paradigm change due to built-in
      interest in negating the influence of environment. Those who are against
      evolution, of course, cannot be expected to understand the role of environment in
      evolution. Those for it, many biologists included, believing in the supremacy of
      genes empowers them by giving adaptation a solely gene-directed (self-driven)
      "teleological" interpretation. 

PMID- 25985892
TI  - Many multicenter trials had few events per center, requiring analysis via random
      effects models or GEEs.
AB  - OBJECTIVES: Adjustment for center in multicenter trials is recommended when there
      are between-center differences or when randomization has been stratified by
      center. However, common methods of analysis (such as fixed-effects, Mantel
      Haenszel, or stratified Cox models) often require a large number of patients or
      events per center to perform well. STUDY DESIGN AND SETTING: We reviewed 206
      multicenter randomized trials published in four general medical journals to
      assess the average number of patients and events per center and determine whether
      appropriate methods of analysis were used in trials with few patients or events
      per center. RESULTS: The median number of events per center/treatment arm
      combination for trials using a binary or survival outcome was 3 (interquartile
      range, 1-10). Sixteen percent of trials had less than 1 event per
      center/treatment combination, 50% fewer than 3, and 63% fewer than 5. Of the
      trials which adjusted for center using a method of analysis which requires a
      large number of events per center, 6% had less than 1 event per center-treatment
      combination, 25% fewer than 3, and 50% fewer than 5. Methods of analysis that
      allow for few events per center, such as random-effects models or generalized
      estimating equations (GEEs), were rarely used. CONCLUSION: Many multicenter
      trials contain few events per center. Adjustment for center using random-effects
      models or GEE with model-based (non-robust) standard errors may be beneficial in
      these scenarios.

PMID- 25985893
TI  - Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.
AB  - BACKGROUND: Colorectal cancer is the third most common cancer and a major cause
      of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the
      standard of care in patients with UICC stage III colon cancer after R0 resection.
      Adjuvant therapy was not shown to be beneficial in patients with UICC stage II
      colon cancer. However, there is an ongoing discussion as to whether adjuvant
      chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk
      situation" (such as T4). METHODS: We investigated a Bavarian population-based
      (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated
      between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large
      (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients,
      240 had a T4 tumor (12%); 77 of all T4 patients received postoperative
      chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for
      survival analyses. RESULTS: Patients with a T4 tumor who received postoperative
      chemotherapy had a highly significant survival benefit in respect of overall
      survival (p<0.001) and recurrence-free survival (p=0.008). However, no difference
      was observed between oxaliplatin-containing and non-oxaliplatin-containing
      treatment regimens. G2 and G3 tumors were found to particularly benefit from
      adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained
      independent risk factors in the multivariate cox regression analysis. CONCLUSION:
      Our retrospective study demonstrated the significant benefit of adjuvant
      chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data
      suggest that adjuvant chemotherapy should be seriously considered in these
      patients.

PMID- 25985895
TI  - Advanced seasonal reproductive development in a male urban bird is reflected in
      earlier plasma luteinizing hormone rise but not energetic status.
AB  - Urban animals inhabit an environment considerably different than do their non
      urban conspecifics, and to persist urban animals must adjust to these novel
      environments. The timing of seasonal reproductive development (i.e., growth of
      gonads and secondary sex organs) is a fundamental determinant of the breeding
      period and is frequently advanced in urban bird populations. However, the
      underlying mechanism(s) by which birds adjust the timing of reproductive
      development to urban areas remain(s) largely unknown. Here, we compared the
      timing of vernal reproductive development in free-ranging urban and non-urban
      male Abert's Towhees, Melozone aberti, in Phoenix, Arizona, USA, and tested the
      non-mutually exclusive hypotheses that earlier reproductive development is due to
      improved energetic status and/or earlier increase in endocrine activity of the
      reproductive system. We found that urban birds initiated testicular development
      earlier than non-urban birds, but this disparity was not associated with
      differences in body condition, fat stores, or innate immune performance. These
      results provide no support for the hypothesis that energetic constraints are
      responsible for delayed reproductive development of non-urban relative to urban
      male Abert's Towhees. Urban birds did, however, increase their plasma luteinizing
      hormone, but not plasma testosterone, earlier than non-urban birds. These
      findings suggest that adjustment to urban areas by Abert's Towhees involves
      increases in the endocrine activity of the anterior pituitary gland and/or
      hypothalamus earlier than non-urban towhees. 

PMID- 25985894
TI  - Dietary methimazole-induced hypothyroidism reduces hepatic lipid deposition by
      down-regulating lipogenesis and up-regulating lipolysis in Pelteobagrus
      fulvidraco.
AB  - The present study was conducted to investigate the effects and mechanisms of
      hypothyroidism, induced by administration of 0.2% methimazole through the food,
      on lipid metabolism in the liver of juvenile yellow catfish Pelteobagrus
      fulvidraco. To this end, yellow catfish were fed diets containing either 0 or 2g
      methimazole per kg of diet for 8weeks, respectively. The results showed that fish
      fed diet containing methimazole had a significant reduction in growth
      performance, plasma THs levels and hepatic lipid content. Meanwhile, methimazole
      treatment inhibited the activities of lipogenic enzymes (6-phosphogluconate
      dehydrogenase, glucose 6-phosphate dehydrogenase, malic enzyme, isocitrate
      dehydrogenase and fatty acid synthase) and the mRNA levels of genes involved in
      lipogenesis (6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase,
      fatty acid synthase, acetyl-CoA carboxylase alpha, sterol-regulator element
      binding protein-1 and liver X receptor), but increased lipolytic enzyme
      (carnitine palmitoyltransferase 1) activity and the expression of genes involved
      in lipolysis (carnitine palmitoyltransferase 1a, hormone-sensitive lipase and
      peroxisome proliferators-activated receptor alpha). Thus, our study indicated
      that dietary methimazole-induced hypothyroidism could disturb the normal
      processes of lipid metabolism at the enzymatic and molecular levels in yellow
      catfish, and the reduced hepatic lipid content by hypothyroidism was attributable
      to the down-regulation of lipogenesis and up-regulation of lipolysis. 

PMID- 25985896
TI  - When a discriminating dose assay is not enough: measuring the intensity of
      insecticide resistance in malaria vectors.
AB  - BACKGROUND: Guidelines from the World Health Organization for monitoring
      insecticide resistance in disease vectors recommend exposing insects to a
      predetermined discriminating dose of insecticide and recording the percentage
      mortality in the population. This standardized methodology has been widely
      adopted for malaria vectors and has provided valuable data on the spread and
      prevalence of resistance. However, understanding the potential impact of this
      resistance on malaria control requires a more quantitative measure of the
      strength or intensity of this resistance. METHODS: Bioassays were adapted to
      quantify the level of resistance to permethrin in laboratory colonies and field
      populations of Anopheles gambiae sensu lato. WHO susceptibility tube assays were
      used to produce data on mortality versus exposure time and CDC bottle bioassays
      were used to generate dose response data sets. A modified version of the CDC
      bottle bioassay, known as the Resistance Intensity Rapid Diagnostic Test (I-RDT),
      was also used to measure the knockdown and mortality after exposure to different
      multipliers of the diagnostic dose. Finally cone bioassays were used to assess
      mortality after exposure to insecticide treated nets. RESULTS: The time response
      assays were simple to perform but not suitable for highly resistant populations.
      After initial problems with stability of insecticide and bottle washing were
      resolved, the CDC bottle bioassay provided a reproducible, quantitative measure
      of resistance but there were challenges performing this under field conditions.
      The I-RDT was simple to perform and interpret although the end point selected
      (immediate knockdown versus 24 h mortality) could dramatically affect the
      interpretation of the data. The utility of the cone bioassays was dependent on
      net type and thus appropriate controls are needed to interpret the operational
      significance of these data sets. CONCLUSIONS: Incorporating quantitative measures
      of resistance strength, and utilizing bioassays with field doses of insecticides,
      will help interpret the possible impact of resistance on vector control
      activities. Each method tested had different benefits and challenges and
      agreement on a common methodology would be beneficial so that data are generated
      in a standardized format. This type of quantitative data are an important
      prerequisite to linking resistance strength to epidemiological outcomes.

PMID- 25985897
TI  - Wilderness in the 'city' revisited: different urbes shape transmission of
      Echinococcus multilocularis by altering predator and prey communities.
AB  - The urbanization of Echinococcus multilocularis, the agent of alveolar
      echinococcosis (AE), is a public health concern worldwide. Here we propose to
      consider 'urban' habitats under a broad ecological perspective and discuss the
      effects of human settlements (urbes) on host communities and the process of
      parasite urbanization. We argue that interactions between landscape features
      (i.e., landscape composition and configuration) and host communities can shape
      the heterogeneity of transmission gradients observed within and across different
      types of human settlement. Due to unique ecological characteristics and public
      health management priorities, we envisage urban landscapes as a model system to
      further increase our understanding of host-parasite interactions shaping the
      circulation of E. multilocularis. 

PMID- 25985898
TI  - Assessing the infectious reservoir of falciparum malaria: past and future.
AB  - Renewed interest in malaria eradication has placed greater emphasis on the
      development of tools to interrupt Plasmodium transmission, such as transmission
      blocking vaccines. However, effective deployment of such tools is likely to
      depend on improving our understanding of which individuals transmit infections to
      mosquitoes. To date, only a handful of studies have directly determined the
      infectiousness of individuals in endemic populations. Here we review these
      studies and their relative merits. We also highlight factors influencing
      transmission potential that are not normally considered: the duration of human
      infectiousness, frequency of sampling by mosquitoes, and variation in vector
      competence among different mosquito populations. We argue that more comprehensive
      xenodiagnostic assessments of infectivity are necessary to accurately quantify
      the infectious reservoir and better target interventions. 

PMID- 25985899
TI  - Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on
      Electrophysiological Changes Induced by Myocardial Stretch.
AB  - INTRODUCTION AND OBJECTIVES: Mechanical response to myocardial stretch has been
      explained by various mechanisms, which include Na(+)/H(+) exchanger activation by
      autocrine-paracrine system activity. Drug-induced changes were analyzed to
      investigate the role of these mechanisms in the electrophysiological responses to
      acute myocardial stretch. METHODS: Multiple epicardial electrodes and mapping
      techniques were used to analyze changes in ventricular fibrillation induced by
      acute myocardial stretch in isolated perfused rabbit hearts. Four series were
      studied: control (n = 9); during perfusion with the angiotensin receptor blocker
      losartan (1 MUM, n = 8); during perfusion with the endothelin A receptor blocker
      BQ-123 (0.1 MUM, n = 9), and during perfusion with the Na(+)/H(+) exchanger
      inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 MUM, n = 9). RESULTS: EIPA
      attenuated the increase in the dominant frequency of stretch-induced fibrillation
      (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and
      EIPA=22% [P<.001]). During stretch, the activation maps were less complex
      (P<.0001) and the spectral concentration of the arrhythmia was greater (greater
      regularity) in the EIPA series: control=18 (3%); EIPA = 26 (9%) (P < .02);
      losartan=18 (5%) (not significant); and BQ-123=18 (4%) (not significant).
      CONCLUSIONS: The Na(+)/H(+) exchanger inhibitor EIPA attenuated the
      electrophysiological effects responsible for the acceleration and increased
      complexity of ventricular fibrillation induced by acute myocardial stretch. The
      angiotensin II receptor antagonist losartan and the endothelin A receptor blocker
      BQ-123 did not modify these effects.

PMID- 25985900
TI  - Truncated Ubiquitin 5' Regulatory Region from Erianthus arundinaceus Drives
      Enhanced Transgene Expression in Heterologous Systems.
AB  - Characterization of novel plant gene promoters underpins the development of
      transgenic crop plants. Here, we report a novel 5' regulatory sequence (Eriubi
      D7) of the ubiquitin gene from Erianthus arundinaceus, a wild relative of
      sugarcane resistant to many biotic and abiotic stresses. A 3.2-kb regulatory
      sequence of ubiquitin gene was isolated through random amplification of genomic
      ends technique and characterized in rice, tobacco, and sugarcane. In silico
      analysis revealed that the regulatory sequence contained a promoter region of
      1600 bp upstream to the transcription start site. Between the promoter and the
      coding region, two putative introns of 584 and 583 bp and two putative non-coding
      exons of 459 and 37 bp were spaced alternatively. To identify the active domains
      required for gene regulation, 12 truncations/recombinants were made in the
      regulatory sequence and characterized in heterologous systems. Transformation
      studies with the recombinant constructs revealed that Eriubi D7, a truncated
      fragment containing 830 bp promoter and the intron I, conferred enhanced GUS
      reporter gene expression in both monocots and dicots compared to other routinely
      used promoters such as maize ubi1 and Cauliflower Mosaic Virus 35S. Further
      analysis confirms that this regulatory sequence is quite distinct from the other
      reported ubiquitin promoters and was also found to enhance expression of the
      reporter gene upon wounding. This is the first report on the isolation and
      characterization of a promoter from a wild sugarcane germplasm and is expected to
      be useful for development of transgenic crop plants. 

PMID- 25985901
TI  - Field validation of a Leishmania (Leishmania) mexicana exo-antigens ELISA for
      diagnosing tegumentary leishmaniasis in regions of Leishmania (Viannia)
      predominance.
AB  - BACKGROUND: Several tests are performed to obtain better accuracy when diagnosing
      American tegumentary leishmaniasis (ATL). It is believed that antigens released
      via secretion, excretion and metabolism are more specific than are antigens
      released by the lysis of Leishmania parasites. Such antigens are known as exo
      antigens (exo-Ag) and are formed from products released by cultured parasites in
      a way that is similar to that in which they cause infections in hosts. OBJECTIVE:
      We attempted to validate a Leishmania mexicana ELISA exo-Ag for ATL diagnosis in
      Midwestern Brazil. METHODS: A total of 281 patients were included in the study.
      We analysed pre-treatment blood from 98 ATL patients; out of those, 85.7% and
      14.3% had cutaneous and mucosal forms, respectively. RESULTS: The exo-Ag accuracy
      was 83.99% (95% CI=79.24-87.81) with a sensitivity value of 90.82% (95% CI=83.46
      95.09) and an overall specificity value of 80.33% (95% CI=73.97-85.44). The
      positive predictive value and negative predictive value were 71.20% (95% CI=62.72
      78.41) and 94.23% (95% CI=89.40-96.94), respectively. Among healthy controls, exo
      Ag had a specificity of 91.25% (95% CI=83.02-95.70); additionally, the test had
      specificity rates of 66.67% (95% CI=46.71-82.03) in Chagas disease patients,
      60.61% (95% CI=43.68-75.32) in patients with rheumatic diseases, 76.92% (95%
      CI=49.74-91.82) in pemphigus foliaceus patients, 87.50% (95% CI=52.91-97.76) in
      leprosy patients, 87.50% (95% CI=63.98-96.50) in VRDL-positive patients, and
      77.78 (95% CI=45.26-93.68) in deep mycosis patients. CONCLUSION: Based on the
      indicators of validity, we conclude that the results obtained in this study
      enable the recommendation of the exo-Ag ELISA for ATL diagnosis once it presented
      a reasonable accuracy compared to classical methods. Cost evaluations are
      necessary to completely define the role of this technique in large scale.

PMID- 25985903
TI  - Correlates of Protection for Herpes Zoster Vaccine: Evaluating Candidate
      Immunological Variables.

PMID- 25985902
TI  - Breast Milk as a Potential Source of Epstein-Barr Virus Transmission Among
      Infants Living in a Malaria-Endemic Region of Kenya.
AB  - BACKGROUND: We previously reported that infants in Kenya were infected with
      Epstein-Barr virus (EBV) at <6 months of age, suggesting that mothers were the
      likely source of transmissible virus to the infant. In this study, we
      investigated whether breast milk contained infectious EBV and the role of malaria
      in EBV shedding in breast milk. METHODS: Breast milk samples were obtained from
      Kenyan mothers at postpartum weeks 6, 10, 14, and 18 and analyzed for presence of
      infectious EBV. RESULTS: We found that the prevalence of EBV DNA and the mean EBV
      load were significantly higher at 6 weeks and decreased through postpartum week
      18 (P < .0001). High EBV load in breast milk correlated with mothers who had
      Plasmodium falciparum malaria at delivery. To determine whether viral DNA was
      encapsidated, breast milk samples were treated with DNAse before DNA extraction.
      Sixty percent of samples were DNAse resistant, suggesting that the viral DNA in
      breast milk was encapsidated. Next, we exposed peripheral blood mononuclear cells
      to breast milk supernatant, which resulted in the generation of EBV-positive
      lymphoblastoid cell lines, indicating that the virus in breast milk was
      infectious. CONCLUSIONS: Our data suggest that breast milk contains infectious
      EBV and is a potential source of viral transmission to infants living in malaria
      endemic regions.

PMID- 25985904
TI  - Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote
      Cholangiocytes to Adopt a Tumorigenic Phenotype.
AB  - BACKGROUND: Throughout Asia, there is an unprecedented link between
      cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini.
      Multiple processes, including chronic inflammation and secretion of parasite
      proteins into the biliary epithelium, drive infection toward cancer. Until now,
      the mechanism and effects of parasite protein entry into cholangiocytes was
      unknown. METHODS: Various microscopy techniques were used to identify O.
      viverrini extracellular vesicles (EVs) and their internalization by human
      cholangiocytes. Using mass spectrometry we characterized the EV proteome and
      associated changes in cholangiocytes after EV uptake, and we detected EV proteins
      in bile of infected hamsters and humans. Cholangiocyte proliferation and
      interleukin 6 (IL-6) secretion was measured to assess the impact of EV
      internalization. RESULTS: EVs were identified in fluke culture medium and bile
      specimens from infected hosts. EVs internalized by cholangiocytes drove cell
      proliferation and IL-6 secretion and induced changes in protein expression
      associated with endocytosis, wound repair, and cancer. Antibodies to an O.
      viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes.
      CONCLUSIONS: This is the first time that EVs from a multicellular pathogen have
      been identified in host tissues. Our findings imply a role for O. viverrini EVs
      in pathogenesis and highlight an approach to vaccine development for this
      infectious cancer.

PMID- 25985905
TI  - E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase
      Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient.
AB  - BACKGROUND: An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic
      stem cell transplant recipient during conditioning regimen. He was treated with
      oral oseltamivir, later combined with intravenous zanamivir. The H275Y
      neuraminidase (NA) mutation was first detected, and an E119D NA mutation was
      identified during zanamivir therapy. METHODS: Recombinant wild-type (WT) E119D
      and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics.
      Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay
      using the 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (MUNANA)
      substrate. Susceptibility to favipiravir (T-705) was assessed using plaque
      reduction assays. The NA affinity and velocity values were determined with NA
      enzymatic studies. RESULTS: We identified an influenza A(H1N1)pdm09 E119D mutant
      that exhibited a marked increase in the 50% inhibitory concentrations against all
      tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir,
      and laninamivir, respectively). The double E119D/H275Y mutation further increased
      oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold,
      respectively, compared with the WT. The mutant viruses remained susceptible to
      favipiravir. The NA affinity and velocity values of the E119D variant decreased
      by 8.1-fold and 4.5-fold, respectively, compared with the WT. CONCLUSIONS: The
      actual emergence of a single NA mutation conferring pan-NAI resistance in the
      clinical setting reinforces the pressing need to develop new anti-influenza
      strategies.

PMID- 25985906
TI  - Reply to Dunning.

PMID- 25985907
TI  - Patient and physician factors influence decision-making in hypercholesterolemia:
      a questionnaire-based survey.
AB  - BACKGROUND: Goal attainment of guideline-recommended low-density lipoprotein
      cholesterol (LDL-C) is suboptimal. Little is known about how patient factors
      influence physicians' treatment decision-making in hypercholesterolemia. We
      examined physicians' treatment recommendations in high-risk patients whose LDL-C
      remained uncontrolled despite statin monotherapy. METHODS: Physicians completed a
      questionnaire prior to randomization into period I of a two-period randomized
      controlled trial evaluating LDL-C goal attainment in patients whose LDL-C
      remained >=100 mg/dL after 5 weeks' treatment with atorvastatin 10 mg/day
      (NCT01154036). Physicians' treatment recommendations were surveyed for two
      hypothetical and one real scenario: (1) LDL-C presumed near goal (between 100-105
      mg/dL), (2) LDL-C presumed far from goal (~120 mg/dL), and (3) observed baseline
      LDL-C of enrolled patients. Prognostic factors considered during decision-making
      were identified by regression analysis. Observed lipid outcomes at the end of
      period I (following 6 weeks' treatment with ezetimibe 10 mg plus atorvastatin 10
      mg, atorvastatin 20 mg, or rosuvastatin 10 mg) were compared with estimated LDL-C
      outcomes for physicians' treatment recommendations after 6 weeks (based on
      individual patients' pre-randomization LDL-C and expected incremental change).
      RESULTS: Questionnaires were completed for 1,534 patients. No change in therapy,
      or double atorvastatin dose, were frequently recommended, even when LDL-C was far
      from goal (6.5% and 52.2% of patients, respectively). Double atorvastatin dose
      was commonly recommended in all scenarios (43-52% of patients). More intensive
      LDL-C-lowering regimens were recommended infrequently e.g. double atorvastatin
      dose and add ezetimibe only <12% in all scenarios. Overall, cardiovascular risk
      factors and desire to achieve a more aggressive LDL-C goal were prominent factors
      in decision-making for treatment. Comparison of observed and estimated LDL-C
      levels showed that physicians tended to overestimate the effectiveness of their
      recommendations. CONCLUSIONS: This study provides insight into physicians'
      perspectives on clinical management of hypercholesterolemia and highlights a gap
      in knowledge translation from guidelines to clinical practice. The need for lower
      LDL-C and cardiovascular risk were key drivers in clinical decision-making, but
      physicians' treatment choices were more conservative than guideline
      recommendations, potentially resulting in poorer LDL-C reduction. When compared
      with actual outcomes, projected LDL-C control was better if physicians used more
      comprehensive strategies rather than simply doubling the statin dose. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01154036.

PMID- 25985908
TI  - Dry phantom for magnetoencephalography -Configuration, calibration, and
      contribution.
AB  - BACKGROUND: An artificial object that imitates human brain activity is called
      "phantom" and is used for evaluation of magnetoencephalography (MEG) systems. The
      accuracy of the phantom itself had not been guaranteed in the previous studies,
      although role of the phantom is to evaluate the accuracy of MEG measurement. The
      purposes of this paper are to develop a novel MEG phantom that can be calibrated
      and to demonstrate the advantages of the calibrated phantoms. NEW METHOD: We
      proposed and fabricated a practical dry phantom that is composed of 50 isosceles
      triangle coils based on Ilmoniemi's model. This phantom was calibrated based on
      three-dimensional measurement of the current paths in the phantom and on
      numerical calculations. RESULTS: The calibrated positions of the equivalent
      current dipoles (ECDs) shifted 0.83mm, on average, from the designed positions.
      The uncertainties of the calibrated ECDs were also evaluated, by combining the
      uncertainties which could reasonably be attributed to them. COMPARISON WITH
      EXISTING METHOD(S): Furthermore, we demonstrated performance of the developed
      phantom through experimental evaluation of an MEG system. The results of this
      evaluation differed from those obtained using an uncalibrated phantom. Moreover,
      the calibrated phantom can provide detailed information regarding the uncertainty
      of the measurement and also the uncertainty of the phantom itself. CONCLUSIONS: A
      more appropriate evaluation of MEG measurements can be achieved using a
      calibrated phantom.

PMID- 25985909
TI  - Selective breeding: the future of TB management in African buffalo?
AB  - The high prevalence of bovine tuberculosis (BTB) in African buffalo (Syncerus
      caffer) in regions of southern African has a negative economic impact on the
      trade of animals and animal products, represents an ecological threat to
      biodiversity, and poses a health risk to local communities through the wildlife
      cattle-human interface. Test and cull methods may not be logistically feasible in
      many free-range wildlife systems, and with the presence of co-existing BTB hosts
      and the limited effectiveness of the BCG vaccine in buffalo, there is a need for
      alternative methods of BTB management. Selective breeding for increased
      resistance to BTB in buffalo may be a viable method of BTB management in the
      future, particularly if genetic information can be incorporated into these
      schemes. To explore this possibility, we discuss the different strategies that
      can be employed in selective breeding programmes, and consider the implementation
      of genetic improvement schemes. We reflect on the suitability of applying this
      strategy for enhanced BTB resistance in African buffalo, and address the
      challenges of this approach that must be taken into account. Conclusions and the
      implications for management are presented. 

PMID- 25985910
TI  - Assessment of resistance risk in Musca domestica L. (Diptera: Muscidae) to
      methoxyfenozide.
AB  - Methoxyfenozide, an ecdysone receptor agonist is an effective larvicide against
      many pests of public health and veterinary importance including house fly, Musca
      domestica L. (Diptera: Muscidae). Methoxyfenozide is a bio-rational insecticide
      having many environmentally friendly attributes that make it compatible with
      integrated pest management programs. This experiment was performed for the
      assessment of resistance evolution in M. domestica to methoxyfenozide. A field
      population of M. domestica, after 24 rounds of selection with methoxyfenozide,
      resulted in 64 fold and 915-fold increase in lethal concentration 50 (LC50)
      compared to field and susceptible strain, respectively. Realized heritability
      (h(2)) of resistance to methoxyfenozide was 0.17 in methoxyfenozide-selected
      strain of M. domestica. The projected rate of resistance development indicated
      that, if slope=1.71 and h(2)=0.17, then 13-5 generations are required for tenfold
      increase in LC50 at 50-95% selection intensity. These findings suggest that a
      risk for resistance development to methoxyfenozide occurred in M. domestica under
      continuous selection pressure. 

PMID- 25985911
TI  - Vaccine coverage in CF children: A French multicenter study.
AB  - BACKGROUNDS: Recent reports have pointed the low vaccine coverage in patients
      with chronic diseases. Data are lacking in patients with cystic fibrosis (CF).
      Gaining more information on coverage both for mandatory vaccines and those more
      specifically recommended would help to optimize care of these patients. METHODS:
      Data were extracted from the "MucoFlu" study, which was a prospective study
      performed in 2009 in the 5 cystic fibrosis centers of the Paris metropolitan
      area. Data on mandatory and recommended vaccines in CF were collected in the
      health booklet and compared to the coverage of the general population. RESULTS: A
      total of 134 CF children were included. Vaccination coverage for mandatory
      vaccines was insufficient (DTPCaHi, conjugate pneumococcal, BCG, MMR and
      hepatitis B) at 1year of age with no catching-up with age in contrast to the
      general population. Approximately 66% of the children had immunization for
      seasonal influenza and 91% for 2009 pandemic flu. Coverage for vaccines
      specifically recommended in CF was low for hepatitis A, non conjugate
      pneumococcal and varicella. CONCLUSION: This study shows a defect in vaccine
      coverage for both routine immunization and vaccines more specifically recommended
      in CF.

PMID- 25985912
TI  - Dual-stimuli responsive hyaluronic acid-conjugated mesoporous silica for targeted
      delivery to CD44-overexpressing cancer cells.
AB  - In this paper, a redox and enzyme dual-stimuli responsive delivery system (MSN-SS
      HA) based on mesoporous silica nanoparticles (MSN) for targeted drug delivery has
      been developed, in which hyaluronic acid (HA) was conjugated on the surface of
      silica by cleavable disulfide (SS) bonds. HA possesses many attractive features,
      including acting as a targeting ligand and simultaneously a capping agent to
      achieve targeted and controlled drug release, prolonging the blood circulation
      time, and increasing the physiological stability and biocompatibility of MSN. The
      anticancer drug doxorubicin (DOX) was chosen as a model drug. In vitro drug
      release profiles showed that the release of DOX was markedly restricted in pH 7.4
      and pH 5.0 phosphate buffer solution (PBS), while it was significantly
      accelerated upon the addition of glutathione (GSH)/hyaluronidases (HAase). In
      addition, the release was further accelerated in the presence of both GSH and
      HAase. Confocal laser scanning microscopy (CLSM) and fluorescence-activated cell
      sorting (FACS) showed that MSN-SS-HA exhibited a higher cellular uptake via
      cluster of differentiation antigen-44 (CD44) receptor-mediated endocytosis
      compared with thiol (SH)-functionalized MSN (MSN-SH) in CD44 receptor over
      expressed in human HCT-116 cells. The DOX-loaded MSN-SS-HA was more cytotoxic
      against HCT-116 cells than NIH-3T3 (CD44 receptor-negative) cells due to the
      enhanced cellular uptake of MSN-SS-HA. This paper describes the development of an
      effective method for using a single substance as multi-functional material for
      MSN to simultaneously regulate drug release and achieve targeted delivery. 

PMID- 25985914
TI  - Spontaneous formation of Au-Pt alloyed nanoparticles using pure nano-counterparts
      as starters: a ligand and size dependent process.
AB  - In this work we investigate the formation of PtAu monodisperse alloyed
      nanoparticles by ageing pure metallic Au and Pt small nanoparticles (sNPs),
      nanoparticle size <5 nm, under certain conditions. We demonstrate that those
      bimetallic entities can be obtained by controlling the size of the initial
      metallic sNPs separately prepared and by selecting their appropriate capping
      agents. The formation of this spontaneous phenomenon was studied using HR-STEM,
      EDS, ionic conductivity, UV-Vis spectroscopy and cyclic voltammetry. Depending on
      the type of capping agent used and the size of the initial Au sNPs, three
      different materials were obtained: (i) AuPt bimetallic sNPs showing a surface
      rich in Au atoms, (ii) segregated Au and Pt sNPs and (iii) a mixture of
      bimetallic nanoparticles as well as Pt sNPs and Au NPs. Surface segregation
      energies and the nature of the reaction environment are the driving forces to
      direct the distribution of atoms in the bimetallic sNPs. PtAu alloyed
      nanoparticles were obtained after 150 h of reaction at room temperature if a weak
      capping agent was used for the stabilization of the nanoparticles. It was also
      found that Au atoms diffuse towards Pt sNPs, producing a surface enriched in Au
      atoms. This study shows that even pure nanoparticles are prone to be modified by
      the surrounding nanoparticles to give rise to new nanomaterials if atomic
      diffusion is feasible.

PMID- 25985916
TI  - Reconstitution of T Cell Immunity after Umbilical Cord Blood Transplantation.

PMID- 25985915
TI  - Corticosteroid-Free Primary Treatment of Chronic Extensive Graft-versus-Host
      Disease Incorporating Rituximab.
AB  - Chronic graft-versus-host disease (cGVHD) is a significant determinant of overall
      outcome and quality of life in survivors of allogeneic hematopoietic cell
      transplantation. Standard initial therapy of cGVHD is based on prolonged use of
      corticosteroids and a calcineurin inhibitor and has not changed for over 3
      decades, despite limited efficacy and long-term toxicity. Rituximab is an
      attractive agent for the upfront treatment of cGVHD because of its favorable
      toxicity profile, efficacy in steroid-refractory cGVHD, and ability to serve as a
      steroid-sparing agent in autoimmune diseases. We hypothesized that a
      corticosteroid-free regimen incorporating rituximab would result in improved
      outcomes when used for the initial treatment of cGVHD. Twenty-five patients
      (median age, 56 years; range, 29 to 77) with extensive cGVHD were enrolled on a
      prospective phase II trial. Enrollment was limited to patients with first onset
      extensive cGVHD requiring systemic immunosuppression and without residual or
      concurrent acute graft-versus-host disease. cGVHD was classified as de novo,
      interrupted, and progressive in 12, 11, and 2 patients, respectively. cGVHD
      severity (National Institutes of Health grade) was mild, moderate, and severe in
      3, 14, and 8 patients, respectively. All patients received rituximab 375 mg/m(2)
      * 4 weekly doses, then 1 dose every 3 months * 4 doses, in addition to
      mycophenolate mofetil and either tacrolimus or sirolimus. No other systemic
      immunosuppression was permitted, and only a short-course of steroids (<=4 weeks)
      was allowed at physician discretion; otherwise, treatment was deemed a failure
      and patients were treated off study. Twenty-two of 25 patients (88%) responded to
      treatment. Of the 22 responding patients, the median time to maximum response was
      161 days (range, 35 to 300 days) with maximum response being complete in 21 of 22
      patients and partial in 1 patient. Excluding the 3 patients taken off study for
      treatment failure, corticosteroids were used sparingly, with only 2 patients
      receiving any steroids for a median of 15 days (range, 13 to 18 days).
      Immunosuppression was discontinued in 17 of 22 evaluable patients (77%) with a
      median time to discontinuation of 300 days (range, 138 to 488 days). After
      immunosuppression discontinuation, cGVHD did recur in 7 patients after a median
      of 166 days (range, 21 to 393 days), requiring reinstitution of systemic
      immunosuppression (estimated cGVHD recurrence rate of 37%). With a median follow
      up of 27 months, estimated 2-year overall survival is 82%. This regimen utilizing
      rituximab in the initial therapy of cGVHD is effective and avoids the use of
      corticosteroids in the majority of patients. In permitting early discontinuation
      of immunosuppression while obviating the need for prolonged exposure to systemic
      corticosteroids, this regimen may result in reduced treatment-related morbidity
      and mortality associated with cGVHD and its treatment.

PMID- 25985913
TI  - Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous
      microdialysis implants on macrophage activation in rats.
AB  - Macrophage activation is of interest in the biomaterials field since macrophages
      with an M(Dex) characteristic phenotype, i.e., CD68(+)CD163(+), are believed to
      result in improved integration of the biomaterial as well as improved tissue
      remodeling and increased biomaterial longevity. To facilitate delivery of a
      macrophage modulator, dexamethasone-21-phosphate (Dex), microdialysis probes were
      subcutaneously implanted in male Sprague-Dawley rats. Dex localized delivery was
      delayed to the third day post implantation as a means to alter macrophage
      activation state at an implant site. To better elucidate the molecular mechanisms
      associated with M(Dex) macrophage activation, CCL2 was quantified in dialysates,
      gene expression ratios were determined from excised tissue surrounding the
      implant, histological analyses, and immunohistochemical analyses (CD68, CD163)
      were performed. Delayed Dex infusion resulted in the up-regulation of IL-6 at the
      transcript level in the tissue in contact with the microdialysis probe and
      decreased CCL2 concentrations collected in dialysates. Histological analyses
      showed increased cellular density as compared to controls in response to delayed
      Dex infusion. Dex delayed infusion resulted in an increased percentage of
      CD68(+)CD163(+), M(Dex), macrophages in the tissue surrounding the microdialysis
      probe as compared to probes that served as controls. 

PMID- 25985917
TI  - Granulocyte Colony-Stimulating Factor Induces Osteoblast Inhibition by B
      Lymphocytes and Osteoclast Activation by T Lymphocytes during Hematopoietic
      Stem/Progenitor Cell Mobilization.
AB  - In the bone marrow (BM), hematopoietic stem and progenitor cells (HSPCs) reside
      in specialized niches near osteoblast cells at the endosteum. HSPCs that egress
      to peripheral blood are widely used for transplant, and mobilization is most
      commonly performed with recombinant human granulocyte colony-stimulating factor
      (G-CSF). However, the cellular targets of G-CSF that initiate the mobilization
      cascade and bone remodeling are not completely understood. Here, we examined
      whether T and B lymphocytes modulate the bone niche and influence HSPC
      mobilization. We used T and B defective mice to show that G-CSF-induced
      mobilization of HSPCs correlated with B lymphocytes but poorly with T
      lymphocytes. In addition, we found that defective B lymphocytes prevent G-CSF
      mediated osteoblast disruption, and further study showed BM osteoblasts were
      reduced coincident with mobilization, induced by elevated expression of dickkopf1
      of BM B lymphocytes. BM T cells were also involved in G-CSF-induced osteoclast
      activation by regulating the Receptor Activator of Nuclear Factor-kappa B
      Ligand/Osteoprotegerin (RANKL/OPG) axis. These data provide evidence that BM B
      and T lymphocytes play a role in G-CSF-induced HSPC mobilization by regulating
      bone remodeling.

PMID- 25985918
TI  - The Effect of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation on
      Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review with Meta
      Analysis.
AB  - Stem cell transplantation has been considered a possible therapeutic method for
      neuropathic pain. However, no quantitative data synthesis of stem cell therapy
      for neuropathic pain exists. Therefore, the present systematic review and meta
      analysis assessed the efficacy of bone marrow mesenchymal stem cell (BMMSC)
      transplantation on alleviating pain symptoms in animal models of neuropathic
      pain. In the present meta-analysis, controlled animal studies assessing the
      effect of administrating BMMSC on neuropathic pain were included through an
      extensive literature search of online databases. After collecting data, effect
      sizes were computed and the standardized mean difference (SMD) with 95%
      confidence interval (CI) was entered in all analyses. Random-effects models were
      used for data analysis. Sensitivity and subgroup analyses were performed to
      investigate expected or measured heterogeneity. Finally, 14 study were included.
      The analyses showed that BMMSC transplantation lead to significant improvement on
      allodynia (SMD = 2.06; 95% CI, 1.09 to 3.03; I(2) = 99.7%; P < .001). The type of
      neuropathy (P = .036), time between injury and intervention (P = .02), and the
      number of transplanted cells (P = .023) influence the improvement of allodynia
      after BMMSC transplantation. BMMSC transplantation has no effect on hyperalgesia
      (SMD = .3; 95% CI, -1.09 to 1.68; I(2) = 100%; P < .001) unless it occurs during
      the first 4 days after injury (P = .02). The present systematic review with meta
      analysis suggests that BMMSC transplantation improves allodynia but does not have
      any significant effect on hyperalgesia unless it is given during the first 4 days
      after injury.

PMID- 25985920
TI  - Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord
      Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid
      Leukemia: A Retrospective Study in Japan.
AB  - Granulocyte colony-stimulating factor (G-CSF) increases the susceptibility of
      dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside
      (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF-combined
      conditioning before allogeneic stem cell transplantation might positively
      contribute to decreased incidences of relapse and graft failure without having to
      increase the dose of cytotoxic drugs. We conducted a retrospective nationwide
      study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary
      acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT)
      who underwent 4 different kinds of conditioning regimens: total body irradiation
      (TBI) >= 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI >= 8 Gy + Ara-C
      + CY (n = 119), TBI >= 8 Gy + other (n = 104), or TBI < 8 Gy or non-TBI (n = 48).
      The TBI >= 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence
      of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10
      to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to
      .82; P = .008) rates compared with those without a G-CSF regimen. This
      retrospective study shows that the G-CSF-combined conditioning regimen provides
      better engraftment and survival results in CBT for adults with MDS and sAML.

PMID- 25985919
TI  - Complement-Binding Donor-Specific Anti-HLA Antibodies and Risk of Primary Graft
      Failure in Hematopoietic Stem Cell Transplantation.
AB  - Detection of donor-specific anti-HLA antibodies (DSA) has been associated with
      graft rejection in all forms of transplantation. The mechanism by which DSA
      increase the risk of graft failure remains unclear. We hypothesized that
      complement-binding DSA are associated with engraftment failure in hematopoietic
      stem cell transplantation (HSCT) and analyzed 122 haploidentical transplant
      recipients tested prospectively for DSA. Retrospective analysis to detect C1q
      binding DSA (C1q+DSA) was performed on 22 allosensitized recipients. Twenty-two
      of 122 patients (18%) had DSA, 19 of which were women (86%). Seven patients with
      DSA (32%) rejected the graft. Median DSA level at transplant for patients who
      failed to engraft was 10,055 mean fluorescence intensity (MFI) versus 2065 MFI
      for those who engrafted (P = .007). Nine patients with DSA were C1q positive in
      the initial samples with median DSA levels of 15,279 MFI (range, 1554 to 28,615),
      compared with 7 C1q-negative patients with median DSA levels of 2471 MFI (range,
      665 to 12,254) (P = .016). Of 9 patients who were C1q positive in the initial
      samples, 5 patients remained C1q positive at time of transplant (all with high
      DSA levels [median, 15,279; range, 6487 to 22,944]) and experienced engraftment
      failure, whereas 4 patients became C1q negative pretransplant and all engrafted
      the donor cells (P = .008). In conclusion, patients with high DSA levels (>5000
      MFI) and complement-binding DSA antibodies (C1q positive) appear to be at much
      higher risk of primary graft failure. The presence of C1q+DSA should be assessed
      in allosensitized patients before HSCT. Reduction of C1q+DSA levels might prevent
      engraftment failure in HSCT.

PMID- 25985923
TI  - How perceived predation risk shapes patterns of aging in water fleas.
AB  - Predation is an important selection pressure which shapes aging patterns in
      natural populations, and it is also a significant factor in the life history
      decisions of individuals. Exposure to the perceived threat of size-dependent fish
      predation has been shown to trigger adaptive responses in animal life history
      including an increase in early reproductive output. In water fleas, this response
      to perceived predation risk appears to have a cost, as a lifespan in an
      environment free of predation cues is 20% longer. The aim of this study is to
      establish the biodemographic basis of phenotypic differences in the water flea
      lifespan which are induced by the cues of fish predation. We examined mortality
      by fitting the Gompertz-Makeham model of mortality to large cohorts of two
      cladoceran species, Daphnia longispina and Diaphanosoma brachyurum. Our findings
      indicate that perceived exposure to the threat of fish predation (induced through
      chemical cues) only accelerated the rate of aging in Diaphanosoma, and not in
      Daphnia where the treatment led to an earlier onset of aging. The second of these
      two phenotypic responses is consistent with the genetically based differences
      between Daphnia from habitats that differ with respect to predation risk. In
      contrast, the response of Diaphanosoma demonstrates that the cue of extrinsic
      mortality-in this case, fish predation-is a key factor in shaping these
      cladoceran life histories in the wild, and is one of the few interventions which
      has been shown to induce a plastic change in the rate of aging. 

PMID- 25985924
TI  - Effects of load carriage and footwear on spatiotemporal parameters, kinematics,
      and metabolic cost of walking.
AB  - Gait patterns are commonly altered when walking or running barefoot compared to
      shod conditions. Although controversy exists as to whether barefoot conditions
      result in lower metabolic costs, it is clear that adding load to the body results
      in increased metabolic costs. The effects of footwear and backpack loading have
      been investigated separately, but it is unclear whether manipulating both
      simultaneously would cause similar outcomes. Twelve healthy individuals (7
      female, 5 male) with no obvious gait abnormalities participated in this study
      (age=24+/-2 years, height=1.73+/-0.13 m, and mass=71.1+/-16.9 kg). Steady state
      metabolic data and 3D motion capture were collected during treadmill walking at
      1.5 ms(-1) in four conditions: Barefoot Unloaded, Shod Unloaded, Barefoot Loaded,
      and Shod Loaded. Barefoot walking elicited shorter stride lengths, stance and
      double support times, as well as a slight (~1%), but not significant, decrease in
      metabolic cost. Loading increased metabolic costs of walking but did not elicit
      spatiotemporal changes in either footwear condition. Lower limb kinematic
      differences were noted in response to both loading and footwear. Changes in
      spatiotemporal parameters observed when walking barefoot were not exacerbated by
      the addition of a backpack load. This suggests that the increased metabolic
      demand associated with the load is met with a similar spatiotemporal pattern
      whether a person wears a supportive shoe or not. Thus, the discomfort associated
      with foot strike while barefoot that promotes spatiotemporal changes seems to be
      independent of load.

PMID- 25985922
TI  - Structure and correlates of self-reported empathy in schizophrenia.
AB  - Research on empathy in schizophrenia has relied on dated self-report scales that
      do not conform to contemporary social neuroscience models of empathy. The current
      study evaluated the structure and correlates of the recently-developed
      Questionnaire of Cognitive and Affective Empathy (QCAE) in schizophrenia. This
      measure, whose structure and validity was established in healthy individuals,
      includes separate scales to assess the two main components of empathy: Cognitive
      Empathy (assessed by two subscales) and Affective Empathy (assessed by three
      subscales). Stable outpatients with schizophrenia (n = 145) and healthy
      individuals (n = 45) completed the QCAE, alternative measures of empathy, and
      assessments of clinical symptoms, neurocognition, and functional outcome.
      Exploratory and confirmatory factor analyses provided consistent support for a
      two-factor solution in the schizophrenia group, justifying the use of separate
      cognitive and affective empathy scales in this population. However, one of the
      three Affective Empathy subscales was not psychometrically sound and was excluded
      from further analyses. Patients reported significantly lower Cognitive Empathy
      but higher Affective Empathy than controls. Among patients, the QCAE scales
      showed significant correlations with an alternative self-report empathy scale,
      but not with performance on an empathic accuracy task. The QCAE Cognitive Empathy
      subscales also showed significant, though modest, correlations with negative
      symptoms and functional outcome. These findings indicate that structure of self
      reported empathy is similar in people with schizophrenia and healthy subjects,
      and can be meaningfully compared between groups. They also contribute to emerging
      evidence that some aspects of empathy may be intact or hyper-responsive in
      schizophrenia.

PMID- 25985921
TI  - National Institutes of Health Consensus Development Project on Criteria for
      Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial
      Design Working Group Report.
AB  - Treatment of chronic graft-versus-host disease is intended to produce a
      sustainable benefit by reducing symptom burden, controlling objective
      manifestations of disease activity, preventing damage and impairment, and
      improving overall survival without causing disproportionate harms related to the
      treatment itself. Successful management can control the disease until systemic
      treatment is no longer needed. The complexity of the disease, the extended
      duration of follow-up needed to observe disease resolution and withdrawal of
      immunosuppressive treatment, and the lack of fully developed shorter term
      endpoints impede progress in the field. Identification and characterization of
      primary endpoints demonstrating clinical benefit without requiring years of
      follow-up is urgently needed, with the understanding that clinical benefit
      encompasses not only the self-evident benefit of the primary endpoint but also
      any other associated benefits. This report discusses regulatory considerations,
      eligibility criteria, the value of controlled trial designs, the merits of
      proposed primary endpoints, and key considerations elaborated from experience and
      progress during the past decade. The report concludes by mapping an overall
      approach that could support and lead to maximally informative clinical trials,
      especially those that seek to demonstrate clinical benefit along a pathway to
      regulatory review and approval. 

PMID- 25985926
TI  - A novel green approach for the chemical modification of silica particles based on
      deep eutectic solvents.
AB  - Deep eutectic solvents (DESs), as a novel class of green solvents, were
      successfully applied as eco-friendly and sustainable reaction media for fast
      surface modification of spherical porous silica, resulting in stationary phases
      for high-performance liquid chromatography. The new reaction media were
      advantageous over organic solvents in many aspects, such as the high
      dispersibility of silica spheres and their non-volatility. 

PMID- 25985925
TI  - Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B
      cells with a homologous repertoire in unrelated subjects.
AB  - BACKGROUND: Peanut oral immunotherapy (PNOIT) induces persistent tolerance to
      peanut in a subset of patients and induces specific antibodies that might play a
      role in clinical protection. However, the contribution of induced antibody clones
      to clinical tolerance in PNOIT is unknown. OBJECTIVE: We hypothesized that PNOIT
      induces a clonal, allergen-specific B-cell response that could serve as a
      surrogate for clinical outcomes. METHODS: We used a fluorescent Ara h 2 multimer
      for affinity selection of Ara h 2-specific B cells and subsequent single-cell
      immunoglobulin amplification. The diversity of related clones was evaluated by
      means of next-generation sequencing of immunoglobulin heavy chains from
      circulating memory B cells with 2x250 paired-end sequencing on the Illumina MiSeq
      platform. RESULTS: Expression of class-switched antibodies from Ara h 2-positive
      cells confirms enrichment for Ara h 2 specificity. PNOIT induces an early and
      transient expansion of circulating Ara h 2-specific memory B cells that peaks at
      week 7. Ara h 2-specific sequences from memory cells have rates of nonsilent
      mutations consistent with affinity maturation. The repertoire of Ara h 2-specific
      antibodies is oligoclonal. Next-generation sequencing-based repertoire analysis
      of circulating memory B cells reveals evidence for convergent selection of
      related sequences in 3 unrelated subjects, suggesting the presence of similar Ara
      h 2-specific B-cell clones. CONCLUSIONS: Using a novel affinity selection
      approach to identify antigen-specific B cells, we demonstrate that the early
      PNOIT-induced Ara h 2-specific B-cell receptor repertoire is oligoclonal and
      somatically hypermutated and shares similar clonal groups among unrelated
      subjects consistent with convergent selection.

PMID- 25985927
TI  - Investigating the inclusion properties of aromatic amino acids complexing beta
      cyclodextrins in model peptides.
AB  - Cyclodextrins are commonly used as complexing agents in biological,
      pharmaceutical, and industrial applications since they have an effect on protein
      thermal and proteolytic stability, refolding yields, solubility, and taste
      masking. beta-cyclodextrins (beta-CD), because of their cavity size are a
      perfectly suited complexing agent for many common guest moieties. In the case of
      peptide-cyclodextrin and protein-cyclodextrin host-guest complexes the aromatic
      amino acids are reported to be the principal responsible of the interaction. For
      these reasons, we have investigated the inclusion properties of nine designed
      tripeptides, obtained permuting the position of two L-alanines (Ala, A) with that
      of one L-tryptophan (Trp, W), L-phenylalanine (Phe, F), or L-tyrosine (Tyr, Y),
      respectively. Interestingly, the position of the aromatic side-chain in the
      sequence appears to modulate the beta-CD:peptide binding constants, determined
      via UV-Vis and NMR spectroscopy, which in turn assumes values higher than those
      reported for the single amino acid. The tripeptides containing a tyrosine showed
      the highest binding constants, with the central position in the Ac-AYA-NH2
      peptide becoming the most favorite for the interaction. A combined NMR and
      Molecular Docking approach permitted to build detailed complex models,
      highlighting the stabilizing interactions of the neighboring amino acids backbone
      atoms with the upper rim of the beta-CD. 

PMID- 25985928
TI  - Synthesis and properties of 2'-O,4'-C-spirocyclopropylene bridged nucleic acid
      (scpBNA), an analogue of 2',4'-BNA/LNA bearing a cyclopropane ring.
AB  - 2'-O,4'-C-Spirocyclopropylene bridged nucleic acid (scpBNA), an analogue of 2'
      O,4'-C-methylene bridged nucleic acid (2',4'-BNA/LNA) bearing a cyclopropane ring
      at the 6'-position, was synthesized and successfully incorporated into
      oligonucleotides. The scpBNA-modified oligonucleotides showed excellent duplex
      forming ability with complementary single-stranded RNA and exhibited increased
      enzymatic stability as compared to the corresponding natural and 2',4'-BNA/LNA
      modified oligonucleotides. Our results demonstrate the potential of scpBNA for
      gene therapeutics, such as antisense technology. 

PMID- 25985929
TI  - Counterion-Specific Protein Adsorption on Polyelectrolyte Brushes.
AB  - Protein adsorption is an important issue in biorelated fields. We have
      investigated the protein adsorption on the poly(ionic liquid) (PIL) brushes in
      the presence of different types of counterions. The protein adsorption is driven
      by a decrease in osmotic pressure within the brushes with an increase in entropy
      via the release of counterions. Our study demonstrates that counterion
      specificity has a significant influence on protein adsorption on the PIL brushes.
      There have been two different regimes for counterion-specific protein adsorption.
      When the released counterions cannot bind to the protein surface, the counterion
      specific protein adsorption is dominated by the ion-specific counterion
      condensation within the PIL brushes. If the released counterions can bind to the
      protein surface, then counterion-specific protein adsorption is dominated by the
      ion-specific rebinding of released counterions on the protein surface. This work
      opens up a new opportunity for controlling protein adsorption on polyelectrolyte
      brushes. 

PMID- 25985931
TI  - Mutation analysis of Chinese sporadic congenital sideroblastic anemia by targeted
      capture sequencing.
AB  - BACKGROUND: Congenital sideroblastic anemias (CSAs) comprise a group of
      heterogenous genetic diseases that are caused by the mutation of various genes
      involved in heme biosynthesis, iron-sulfur cluster biogenesis, or mitochondrial
      solute transport or metabolism. However, approximately 40% of patients with CSA
      have not been found to have pathogenic gene mutations. In this study, we
      systematically analyzed the mutation profile in 10 Chinese patients with sporadic
      CSA. FINDINGS: We performed targeted deep sequencing analysis in ten patients
      with CSA using a panel of 417 genes that included known CSA-related genes.
      Mitochondrial genomes were analyzed using next-generation sequencing with a
      mitochondria enrichment kit and the HiSeq2000 sequencing platform. The results
      were confirmed by Sanger sequencing. The ALAS2 mutation was detected in one
      patient. SLC25A38 mutations were detected in three patients, including three
      novel mutations. Mitochondrial DNA deletions were detected in two patients. No
      disease-causing mutations were detected in four patients. CONCLUSION: To our
      knowledge, the pyridoxine-effective mutation C471Y of ALAS2, the compound
      heterozygous mutation W87X, I143Pfs146X, and the homozygous mutation R134C of
      SLC25A38 were found for the first time. Our findings add to the number of
      reported cases of this rare disease and to the CSA pathogenic mutation database.
      Our findings expand the phenotypic profile of mitochondrial DNA deletion
      mutations. This work also demonstrates the application of a congenital blood
      disease assay and targeted capture sequencing for the genetic screening analysis
      and diagnosis of heterogenous genetic CSA.

PMID- 25985932
TI  - Compositional effects on leaching of stain-guarded (perfluoroalkyl and
      polyfluoroalkyl substance-treated) carpet in landfill leachate.
AB  - Perfluoroalkyl and polyfluoroalkyl substances (PFASs) from stain-guard treated
      carpets in landfills continue to be released into the environment. To understand
      the leaching of PFASs from carpets to landfill leachate as a function of
      environmental factors, leaching concentrations of ten perfluoroalkyl carboxylic
      acids and four perfluoroalkyl sulfonic acids were quantified for different pHs,
      contact times, mixing speeds, and temperatures. Partitioning from carpet to
      leachate and distilled water at different pHs showed negligible differences. The
      total concentration of leaching PFASs in distilled water was approximately 1 ng
      L(-1) higher than in landfill leachate, indicating that the presence of
      multivalent cations in leachate could have a negative effect on leaching of
      PFASs. For all PFASs monitored, leaching increased with increasing contact time
      and temperature. Perfluorohexanoic and perfluoroheptanoic acids experienced the
      largest increases with contact time and temperature. Gibbs free energy (DeltaG >
      0), enthalpy (DeltaH > 0), and entropy energy (DeltaS < 0) indicated that PFAS
      leaching from carpet was dominantly controlled by entropy-driven processes and
      did not differ significantly among individual PFASs. PFAS concentrations in
      leachate with rotation of an end-over-end contactor were higher than under static
      conditions, but otherwise, varying the rotation speed had negligible influence.
      The results provide useful information for management of discarded stain-guard
      carpets in landfills. 

PMID- 25985930
TI  - Bacterial Community Composition in Oligosaline Lake Bosten: Low Overlap of
      Betaproteobacteria and Bacteroidetes with Freshwater Ecosystems.
AB  - Oligosaline lakes in arid regions provide indispensable water resources for
      humans; however, information on the bacterial community composition (BCC) of this
      ecosystem is limited. In the present study, we explored seasonal and vertical
      variations in BCC in Lake Bosten, a unique oligosaline lake (1.20/00 salinity) in
      arid, northwestern China, using denaturing gradient gel electrophoresis and 16S
      rRNA gene sequencing. We obtained 544 clones and 98 operational taxonomic units
      (OTUs) from six clone libraries. The top 10 OTUs represented 59.4% of the entire
      bacterial community. Betaproteobacteria (22.1%), Gammaproteobacteria (19.9%),
      Bacteroidetes (18.8%), and Firmicutes (11.4%) dominated in Lake Bosten. Although
      seasonal variations were recorded in BCC, the vertical changes observed were not
      significant. Water temperature and salinity were the most important factors
      shaping the dynamics of BCC. A low degree of overlap was observed in BCC between
      Lake Bosten and freshwater ecosystems, especially for Betaproteobacteria and
      Bacteroidetes. An RDP seqmatch analysis showed that 169 sequences (31%) were
      novel bacterial sequences (<97% similarity to the closest sequences in GenBank),
      which suggested that specific indigenous bacteria inhabit this oligosaline
      environment. Our results support bacterial endemicity being more common than
      previously considered, particularly in oligosaline lakes. An analysis of these
      communities may reveal how bacteria respond to increases in salinity and
      nutrients in the early stage of salinization and eutrophication. 

PMID- 25985934
TI  - Multilayer Capsules of Bovine Serum Albumin and Tannic Acid for Controlled
      Release by Enzymatic Degradation.
AB  - With the purpose to replace expensive and significantly cytotoxic positively
      charged polypeptides in biodegradable capsules formed via Layer-by-Layer (LbL)
      assembly, multilayers of bovine serum albumin (BSA) and tannic acid (TA) are
      obtained and employed for encapsulation and release of model drugs with different
      solubility in water: hydrophilic-tetramethylrhodamine-isothiocyanate-labeled BSA
      (TRITC-BSA) and hydrophobic 3,4,9,10-tetra-(hectoxy-carbonyl)-perylene (THCP).
      Hydrogen bonding is proposed to be predominant within thus formed BSA/TA films.
      The TRITC-BSA-loaded capsules comprising 6 bilayers of the protein and polyphenol
      are benchmarked against the shells composed of dextran sulfate (DS) and poly-l
      arginine (PARG) on degradability by two proteolytic enzymes with different
      cleavage site specificity (i.e., alpha-chymotrypsin and trypsin) and toxicity for
      murine RAW264.7 macrophage cells. Capsules of both types possess low cytotoxicity
      taken at concentrations equal or below 50 capsules per cell, and evident
      susceptibility to alpha-chymotrypsin resulted in release of TRITC-BSA. While the
      BSA/TA-based capsules clearly display resistance to treatment with trypsin, the
      assemblies of DS/PARG extensively degrade. Successful encapsulation of THCP in
      the TRITC-BSA/TA/BSA multilayer is confirmed, and the release of the model drug
      is observed in response to treatment with alpha-chymotrypsin. The thickness,
      surface morphology, and enzyme-catalyzed degradation process of the BSA/TA-based
      films are investigated on a planar multilayer comprising 40 bilayers of the
      protein and polyphenol deposited on a silicon wafer. The developed BSA/TA-based
      capsules with a protease-specific degradation mechanism are proposed to find
      applications in personal care, pharmacology, and the development of drug delivery
      systems including those intravenous injectable and having site-specific release
      capability. 

PMID- 25985938
TI  - Colorectal cancer: POLR2A deletion with TP53 opens a window of opportunity for
      therapy.

PMID- 25985933
TI  - A Review of the Development and Application of Generic Multi-Attribute Utility
      Instruments for Paediatric Populations.
AB  - Multi-attribute utility instruments (MAUIs) are increasingly being used as a
      means of quantifying utility for the calculation of quality-adjusted life-years
      within the context of cost utility analysis. Traditionally, MAUIs have been
      developed and applied in adult populations. However, increasingly, researchers in
      health economics and other disciplines are recognising the importance of the
      measurement and valuation of health in both children and adolescents. Presently,
      there are nine generic MAUIs available internationally that have been used in
      paediatric populations: the Quality of Well-Being Scale (QWB), the Health Utility
      Index Mark 2 (HUI2), the HUI3, the Sixteen-dimensional measure of health-related
      quality of life (HRQoL) (16D), the Seventeen-dimensional measure of HRQoL (17D),
      the Assessment of Quality of Life 6-Dimension (AQoL-6D) Adolescent, the Child
      Health Utility 9D (CHU9D), the EQ-5D Youth version (EQ-5D-Y) and the Adolescent
      Health Utility Measure (AHUM). This paper critically reviews the development and
      application of the above nine MAUIs and discusses the specific challenges of
      health utility measurement in children and adolescents. Areas for further
      research relating to the development and application of generic MAUIs in
      paediatric populations are highlighted. 

PMID- 25985940
TI  - Hand-held echocardiography in the setting of pre-operative cardiac evaluation of
      patients undergoing non-cardiac surgery: results from a randomized pilot study.
AB  - Transthoracic echocardiography is not a routine test in the pre-operative cardiac
      evaluation of patients undergoing non-cardiac surgery but may be considered in
      those with known heart failure and valvular heart disease or complaining cardiac
      symptoms. In this setting, hand-held echocardiography (HHE) could find a
      potential application as an alternative to standard echocardiography in selected
      patients; however, its utility in this context has not been investigated. The aim
      of this pilot study was to evaluate the conclusiveness of HHE compared to
      standard echocardiography in this subset of patients. 100 patients scheduled for
      non-cardiac surgery were randomized to receive a standard exam with a Philips
      Ie33 or a bedside evaluation with a pocket-size imaging device (Opti-Go, Philips
      Medical System). The primary endpoint was the percentage of satisfactory
      diagnosis at the end of the examination referred as conclusiveness. Secondary
      endpoints were the mean duration time and the mean waiting time to perform the
      exams. No significant difference in terms of conclusiveness between HHE and
      standard echo was found (86 vs 96%; P = 0.08). Mean duration time of the
      examinations was 6.1 +/- 1.2 min with HHE and 13.1 +/- 2.6 min with standard
      echocardiography (P < 0.001). HHE resulted in a consistent save of waiting time
      because it was performed the same day of clinical evaluation whereas patients
      waited 10.1 +/- 6.1 days for a standard echocardiography (P < 0.001). This study
      suggests the potential role of HHE for pre-operative evaluation of selected
      patients undergoing non-cardiac surgery, since it provided similar information
      but it was faster and earlier performed compared to standard echocardiography.

PMID- 25985939
TI  - Transarterial approaches to primary and secondary hepatic malignancies.
AB  - Transarterial therapies in the setting of primary and secondary liver
      malignancies are becoming an essential part of the oncology landscape. Most
      patients with hepatic malignancies are not candidates for curative surgical
      intervention, thereby warranting exploration of alternative means of treatment
      that preserves quality of life while providing clinical benefit. Herein, the data
      for intra-arterial chemoinfusion, transarterial chemoembolization, drug-eluting
      beads, and radioembolization are discussed in the setting of malignancies within
      the liver; outcome data relating to survival, time-to-progression, time-to
      recurrence, and adverse events are presented. Further data regarding different
      treatment paradigms for hepatocellular carcinoma, metastatic colorectal
      carcinoma, neuroendocrine tumours, and intrahepatic cholangiocarcinoma are also
      provided. In light of these and forthcoming data, transarterial therapies seem to
      offer a viable treatment pathway for select populations of patients. 

PMID- 25985941
TI  - Extracellular volume fraction in coronary chronic total occlusion patients.
AB  - (1) To assess extracellular volume fraction (ECV) and regional systolic function
      in patients presenting with coronary chronic total occlusion (CTO) in areas
      without significant late gadolinium enhancement (LGE), and (2) to investigate the
      correlation between angiography collateral flow and ECV in territories supplied
      by CTO vessels. A total of 50 angiographically documented CTO patients and 15 age
      and sex-matched normal controls were recruited to the study. Myocardial ECV, was
      calculated in infarcted, global non-infarcted and the entire myocardium
      respectively. Segmental ECV was calculated from myocardial segments within the
      perfusion territory of a CTO vessel. The global and regional systolic function
      was evaluated using ejection fraction and percent systolic thickening. ECVs in
      global myocardium and global non-infarcted myocardium were significantly elevated
      in comparison with that in controls (29.1 +/- 4.2% and 26.6 +/- 2.6% vs. 23.3 +/-
      2.0%, all P < 0.005). Global ECV significantly correlated with LV ejection
      fraction (r = -0.56, P < 0.001) and ECV inversely correlated with systolic
      thickening in global non-infarcted myocardium (r = -0.31, P < 0.05). The lower
      segmental ECV was associated with the presence of well-developed collaterals (P =
      0.004), and multivariate binary logistic analysis demonstrated that mean
      segmental ECV and course of disease were the independent discriminator of
      collateral flow with overall diagnostic accuracy of 74.4%. In patients with CTO,
      ECV is found to be increased beyond that observed with LGE, and correlates with
      LV regional wall motion abnormality, which appears to reflect diffuse myocardial
      fibrosis. Mean segmental ECV value, combined with course of disease, may serve as
      good predictors of collateral flow.

PMID- 25985944
TI  - Numerical simulation of subaqueous chute flows of granular materials.
AB  - In this paper we report on numerical studies of unsteady, gravity-driven flow of
      a subaqueous erodible granular bed on an inclined plane. According to our
      simulations, the evolution of the flow can be partitioned in three phases. In the
      first phase, due to the onset of an interfacial instability, the material
      interface deforms into a series of long waves. In the second phase, these waves
      are transformed to skewed vortex ripples that grow in time and eventually
      coalesce. The computed wavelengths of these ripples are in good agreement with
      previously reported experimental measurements. In the third phase of the flow
      evolution, the high fluid velocities wash out the vortex ripples and a layer of
      rapidly moving particles is formed at the material interface. The predicted
      granular velocities comprise two segments: a concave one at the vicinity of the
      material interface, where the maximum is attained, followed by a slightly convex
      one, where they decrease monotonically to zero. The same trend has been reported
      in experimental results for the corresponding steady flows. Finally, we
      investigate via a parametric study the effect of the configuration stresses,
      which represent contact forces between grains. As it turns out, such stresses
      have a stabilizing effect, in the sense that increasing their magnitude inhibits
      the formation of vortex ripples. 

PMID- 25985943
TI  - Free energy of formation of small ice nuclei near the Widom line in simulations
      of supercooled water.
AB  - The ST2 interaction potential has been used in a large number of simulation
      studies to explore the possibility of a liquid-liquid phase transition (LLPT) in
      supercooled water. Using umbrella sampling Monte Carlo simulations of ST2 water,
      we evaluate the free energy of formation of small ice nuclei in the supercooled
      liquid in the vicinity of the Widom line, the region above the critical
      temperature of the LLPT where a number of thermodynamic anomalies occur. Our
      results show that in this region there is a substantial free-energy cost for the
      formation of small ice nuclei, demonstrating that the thermodynamic anomalies
      associated with the Widom line in ST2 water occur in a well-defined metastable
      liquid phase. On passing through the Widom line, we identify changes in the free
      energy to form small ice nuclei that illustrate how the thermodynamic anomalies
      associated with the LLPT may influence the ice nucleation process. 

PMID- 25985945
TI  - Is Low Vitamin D Status A Risk Factor For Food Allergy? Current Evidence And
      Future Directions.
AB  - Studies from several countries have reported an association between latitudes
      further from the equator and proxy markers of food allergy prevalence. As
      latitudes further from the equator are associated with lower sun exposure and
      vitamin D status (VDS), it has been proposed that low VDS may be a risk factor
      for food allergy. A range of basic science evidence supports the biological
      plausibility of this hypothesis; and recent work has identified a cross sectional
      association between low VDS and challenge proven food allergy in infants.
      Overall, however, the evidence regarding the relationship between VDS and food
      allergy remains controversial and the limited longitudinal data are discouraging.
      In this review we consider the evidence for and against low VDS as a risk factor
      for food allergy and discuss the possibility that other factors (including
      genetic variables) may contribute to the inconsistent nature of the available
      observational evidence. We then discuss whether genetic and/or environmental
      factors may modify the potential influence of VDS on food allergy risk. Finally,
      we argue that given the rising burden of food allergy, the balance of available
      evidence regarding the potential relevance of VDS to this phenomenon, and the
      inherent limitations of the existing observational data, there is a compelling
      case for conducting randomised clinical trials of vitamin D supplementation for
      the prevention of food allergy during early life. 

PMID- 25985946
TI  - Vitamin-D in the Immune System: Genomic and Non-Genomic Actions.
AB  - More than thirty years ago functions of vitamin D other than its beneficial
      effects on calcium homeostasis and bone metabolism have been identified, mainly
      in relation to its antiproliferative effects on cancer cells. Notably, vitamin D
      deficiency has been associated with a number of pathological conditions,
      including infections, autoimmune and allergic diseases. Vitamin D, and its
      metabolites, are actively involved in the regulation of innate and adaptive
      immune responses. Vitamin D signals through the vitamin D receptor (VDR), a
      specific zinc-finger nuclear receptor. The functions of vitamin D are
      characterized as genomic, mediated through the VDR transcriptional effects inside
      the cell nucleus, and non-genomic, when the VDR induces rapid signaling, situated
      on the cell membrane and/or cytoplasm. Emerging evidence supports the notion that
      vitamin D enhances immunity, providing protection towards pathogens, while,
      concomitantly, it exerts immunosuppressive effects by preventing the detrimental
      effects of prolonged inflammatory responses to the host. Still, the precise
      molecular mechanisms involved in vitamin D's genomic and non-genomic actions
      remain incompletely defined. Moreover, it is unclear whether vitamin D actions
      require the synergistic activation of other mediators, such as nuclear membrane
      receptors. Understanding the biology of vitamin D and the molecular pathways
      utilized will pave the way for the design of more effective therapeutic
      strategies. In this review, we present the recent genomic and non-genomic effects
      of vitamin D from an immunological perspective with a focus on immune-mediated
      diseases. 

PMID- 25985947
TI  - Therapeutic Effects of Vitamin D in Asthma and Allergy.
AB  - In recent years, low vitamin D status has been proposed as a putative risk factor
      for allergic diseases. A growing body of literature reports low vitamin D levels
      in atopic patients and supports an association between vitamin D deficiency and
      risk of adverse asthma and allergies outcomes. Therefore, it has been speculated
      that vitamin D supplementation may either prevent or reduce the risk of allergic
      diseases. Birth cohort studies addressing the role of vitamin D intake during
      pregnancy have shown conflicting results regarding allergy outcomes in offspring.
      Currently, only a few studies have tried to supplement vitamin D in asthmatic
      patients, often as an add-on therapy to standard asthma controller medications,
      and results are not all consistent. There is emerging data to show that vitamin D
      can enhance the antiinflammatory effects of glucocorticoids and potentially be
      used as adjuvant therapy in steroid-resistant asthma. Recent in vivo data suggest
      that vitamin D supplementation may also reduce the severity of atopic dermatitis.
      This review examines the existing relevant literature focusing on vitamin D
      supplementation in the treatment of allergic diseases. 

PMID- 25985948
TI  - Vitamin D and Atopic Dermatitis.
AB  - Atopic dermatitis is a chronic inflammatory skin disease that affects a high
      number of children worldwide. It is mainly caused by a disruption of the
      epidermal barrier and an abnormal immune response. Vitamin D might have some
      effects on the innate and adaptive immune system, generally in favour of
      decreasing allergenic mechanisms, as well as it might improve the skin barrier
      and decrease the risk of skin colonization. Thus, an increasing body of evidence
      links this vitamin to atopic dermatitis, although conclusions are not unanimous.
      Many observational studies have shown that low vitamin D serum levels are
      associated with a higher prevalence of this epidermal disease in childhood, but
      others have not. Differences in exposure time, vitamin D dose, age of
      participants, etc. could explain these conflicting results. Moreover, no study
      has been performed to date in order to determine whether variations in vitamin D
      levels at different ages differentially influence the risk of atopic dermatitis.
      A number of randomized controlled trials have tested the usefulness of systemic
      vitamin D as a treatment for this condition, but the results are also
      inconclusive. Nevertheless, topical vitamin D is not recommended because it can
      worsen skin lesions. Narrowband ultraviolet B is used to treat atopic dermatitis,
      although there is little evidence relating this type of phototherapy with
      variations of serum vitamin D levels or to what extent phototherapy benefits are
      mediated through vitamin D. 

PMID- 25985949
TI  - Vitamin D Metabolism Genes in Asthma and Atopy.
AB  - Asthma and allergy are complex diseases influenced by poorly understood
      environmental and genetic factors. The innate and adaptive immune systems play an
      important role in the pathogenesis of these diseases. Many genes involved in
      inflammation and immunoregulation pathways have been related to asthma and
      allergy susceptibility. Among the diverse extra-skeletal actions of vitamin D,
      growing evidence indicates that vitamin D is an important modulator of the immune
      system response and may influence the development of asthma and allergy
      susceptibility through different mechanisms. The vitamin D pathway is under the
      control of a set of polymorphic genes that code for key enzymes which regulate
      the synthesis and metabolism of vitamin D (i.e. CYP27A1, GC, CYP27B1 and CYP24A1)
      and of genes that encode for downstream mediators of vitamin D signalling (i.e.
      VDR, RXR, PPAR, NCOA and SMAD). This metabolism gene pathway is of fundamental
      importance in regulating vitamin D availability and biological response.
      Unravelling the role of vitamin D metabolism genes on asthma and atopy
      susceptibility may help to understand the impact of vitamin D on the development
      of these disorders. This review article aims: 1) to describe the genetics of the
      vitamin D pathway, 2) to revise the potential mechanisms by which vitamin D
      pathway genes may affect the immune and respiratory systems predisposing to
      asthma and allergy disorders; and 3) to summarize the influence of genetic
      variation on vitamin D pathway genes on the development of asthma and allergy. 

PMID- 25985950
TI  - Maternal Vitamin D Status and Development of Asthma and Allergy in Early
      Childhood.
AB  - Vitamin D has an indisputable immunodulatory role in both lung and immune system
      development, which is initiated during fetal life and is mainly accomplished in
      the first years of extrauterine life. Several published studies have shown that
      low levels of vitamin D may increase the risk of developing asthma and allergic
      diseases. Moreover, vitamin D deficiency epidemic reported over the last decades
      coincides with an increase in the prevalence of asthma and allergies in
      westernized societies. Since placental transfer of 25(OH)D is the major source of
      vitamin D in the developing fetus, important questions concerning the impact of
      maternal vitamin D status on the outcome of pregnancy have arisen. The aim of
      this review is to present the current evidence regarding the determinants of
      vitamin D status in pregnancy as well as its role in the development of asthma
      and allergies in early childhood. 

PMID- 25985951
TI  - Association of Serum Vitamin D with Asthma and Atopy in Childhood: Review of
      Epidemiological Observational Studies.
AB  - During the last decades, vitamin D deficiency has re-emerged worldwide affecting
      not only population's bone health, but also several other conditions including
      asthma and allergies. Increasing number of published epidemiological studies in
      the last seven years have examined the role of vitamin D deficiency in childhood
      in several outcomes including asthma diagnosis, asthma disease severity, allergic
      sensitization and atopy. This review presents evidence on this association from a
      systematic search in the literature of all available observational studies and
      their limitations. A total of 33 studies were identified: 3 prospective, 16 case
      control and 14 cross-sectional studies. Overall, most of the case-control studies
      tend to report that asthmatics have lower vitamin D levels/status as compared to
      healthy children, although most of these studies are mainly descriptive in nature
      and tend to provide only crude, unadjusted comparisons. Studies that investigated
      the association of vitamin D with the prevalence, development and/or severity of
      asthma gave mixed findings, with the exception of studies that focused on vitamin
      D and severity of asthma which suggest a positive association of vitamin D levels
      with better asthma control, reduced use of asthma medication, fewer asthma
      exacerbations and lower utilisation of health care facilities for urgent
      treatment. Insufficient evidence also exists for the association of inadequate
      vitamin D status with higher risk of atopic sensitization. The lack of adequate
      number of prospective studies, the variable definitions for case ascertainment,
      the wide age range of the participants, and commonly the inadequate control for
      confounders make inferences difficult. Future studies are needed with a
      prospective design and repeated measurements of vitamin D to provide critical
      information on the timing and dosage of future vitamin D supplementation
      interventions. 

PMID- 25985952
TI  - Recent advances in polymer drug conjugates.
AB  - Polymer drug conjugates play an important role in the delivery of drugs. In the
      polymeric drug conjugates, the bioactive agent is combined covalently with
      polymer to achieve the efficient delivery of bioactive agents in the required or
      specific period of time along with the enhancement of permeability and retention
      time. A large number of biodegradable polymers have been widely used in the area
      of biomedical science. Among them, polyphosphazene, is a biodegradable polymer
      having versatile nature because of its two chlorine atoms attached on both sides
      of phosphorus atom of its polymeric backbone, it can be easily replaced by
      nucleophilic substitution reaction. A plenty of work has been explored for its
      biomedical applications such as tissue engineering, vaccine drug delivery,
      polyphosphazene- anticancer drug conjugates with doxorubicin, paclitaxel,
      platinum complexes, methotrexate and gemcitabine for the targeted drug delivery
      etc. This review is focused on the recent advances in the biomedical applications
      of polyphosphazene-drug conjugates.

PMID- 25985953
TI  - Biopeptides in Milk: Opiate and Antithrombotic Effects.
AB  - Recently, the concept of functional food can be seen worldwide, and there are
      several local wisdoms on health-conscious. In this context, the protein
      fractionation of?milk has attracted interests. Casein-derived bioactives have
      been identified as showing several health beneficial bioactivities including
      opiate, antithrombotic, antioxidative, antimicrobial, osteoprotective,
      anticariogenic and growth-promoting. Peptides have to be absorbed from the
      intestine and reach the target cells in sufficient concentrations or act via
      receptors; then they can show health effects. In this review paper, the milk
      derived peptides and their therapeutic effects are introduced. Also the opiate
      and antithrombotic effects of these peptides are described. 

PMID- 25985954
TI  - Biological and pharmacological activities of 1,3,4-thiadiazole based compounds.
AB  - The chemistry of 1,3,4-thiadiazoles is very well known. A universal and commonly
      used method of the synthesis of different 2,5-disubstituted 1,3,4-thiadiazoles
      includes the cyclization of appropriate linear organic derivatives. They are
      widely known as compounds with various kinds of biological activities showing
      anticancer properties against human cancers and acting as diuretic,
      antibacterial, antifungal, antitubercular and leishmanicidal agents. Many of them
      influence on OUN exhibiting anticonvulsant, anti-inflammatory, antidepressant,
      analgesic and anxiolytic effects. The molecular target of 1,3,4-thiadiazoles
      includes the following enzymes: carbonic anhydrase (CA), cyclooxygenase (CO),
      neutral endopeptidase (NEP), aminopeptidase N (APN), matrix metalloproteinases
      (MMPs), phosphodiesterases (PDEs) and c-Src/Abl tyrosine kinase. In this
      presentation, recent achievements in the medicinal chemistry of 1,3,4-thiadiazole
      based compounds are reviewed.

PMID- 25985955
TI  - Stress, trauma and PTSD: translational insights into the core synaptic circuitry
      and its modulation.
AB  - Evidence is considered as to whether behavioral criteria for diagnosis of post
      traumatic stress disorder (PTSD) are applicable to that of traumatized animals
      and whether the phenomena of acquisition, extinction and reactivation of fear
      behavior in animals are also successfully applicable to humans. This evidence
      suggests an affirmative answer in both cases. Furthermore, the deficits in gray
      matter found in PTSD, determined with magnetic resonance imaging, are also
      observed in traumatized animals, lending neuropsychological support to the use of
      animals to probe what has gone awry in PTSD. Such animal experiments indicate
      that the core synaptic circuitry mediating behavior following trauma consists of
      the amygdala, ventral-medial prefrontal cortex and hippocampus, all of which are
      modulated by the basal ganglia. It is not clear if this is the case in PTSD as
      the observations using fMRI are equivocal and open to technical objections.
      Nevertheless, the effects of the basal ganglia in controlling glutamatergic
      synaptic transmission through dopaminergic and serotonergic synaptic mechanisms
      in the core synaptic circuitry provides a ready explanation for why modifying
      these mechanisms delays extinction in animal models and predisposes towards PTSD.
      In addition, changes of brain-derived neurotrophic factor (BDNF) in the core
      synaptic circuitry have significant effects on acquisition and extinction in
      animal experiments with single nucleotide polymorphisms in the BDNF gene
      predisposing to PTSD.

PMID- 25985956
TI  - Erratum to: Neurons in the lateral part of the lumbar spinal cord show distinct
      novel axon trajectories and are excited by short propriospinal ascending inputs.

PMID- 25985957
TI  - Primary intraosseous meningioma in the calvaria: morphological feature changes on
      magnetic resonance images over several years.
AB  - Primary intraosseous meningiomas (PIMs) are rare, and their pathogenesis remains
      unclear. We report the case of a sizable PIM in the calvaria that progressively
      enlarged over several years and presented temporal changes in the morphological
      features on magnetic resonance images. Along with discussing the case, we further
      emphasize the potential pitfalls of diagnosing a PIM in the calvaria. 

PMID- 25985958
TI  - Venous thromboembolism (VTE) and glioblastoma.
AB  - The risk of venous thromboembolism (VTE) is high for patients with brain tumors
      (11-20 %). Glioblastoma (GBM) patients, in particular, have the highest risk of
      VTE (24-30 %). The Khorana scale is the most commonly used clinical scale to
      evaluate the risk of VTE in cancer patients but its efficacy in patients with GBM
      remains unclear. The aim of this study is to estimate the frequency of VTE in GBM
      patients and identify potential risk factors for the development of VTE during
      adjuvant chemotherapy. Furthermore, we intend to examine whether the Khorana
      scale accurately predicts the risk of VTE in GBM patients. We retrospectively
      reviewed the medical records of GBM patients treated at MD Anderson during the
      years 2005-2011. The study cohort included 440 patients of which 64 (14.5 %)
      developed VTE after the start of adjuvant treatment. The median time to develop
      VTE was 6.5 months from the start of adjuvant treatment. On multivariate analysis
      male sex, BMI >= 35, KPS <= 80, history of VTE and steroid therapy were
      significantly associated with the development of VTE. The Khorana scale was found
      to be an invalid VTE predictive model in GBM patients due to poor specificity. Of
      the 64 patients who developed a VTE, 36 were treated with anticoagulation, 2 with
      an IVC filter, and 21 with both. Complications (intracranial hemorrhage, bleeding
      in other organs and thrombocytopenia) secondary to anticoagulation were reported
      in 16 % (n = 10). VTE is common in patients with GBM. Our results did not
      validate the Khorana scale in GBM patients. Additional studies identifying which
      GBM patients are at highest risk for VTE are needed to enable further evaluation
      of VTE preventive measures in this selected group. 

PMID- 25985959
TI  - Ultrasonography of intrauterine devices.
AB  - The intrauterine device (IUD) is gaining popularity as a reversible form of
      contraception. Ultrasonography serves as first-line imaging for the evaluation of
      IUD position in patients with pelvic pain, abnormal bleeding, or absent retrieval
      strings. This review highlights the imaging of both properly positioned and
      malpositioned IUDs. The problems associated with malpositioned IUDs include
      expulsion, displacement, embedment, and perforation. Management considerations
      depend on the severity of the malposition and the presence or absence of
      symptoms. Three-dimensional ultrasonography has proven to be more sensitive in
      the evaluation of more subtle findings of malposition, particularly side-arm
      embedment. Familiarity with the ultrasonographic features of properly positioned
      and malpositioned IUDs is essential. 

PMID- 25985960
TI  - Patients' Preferences for Information About the Benefits and Risks of Second-Line
      Palliative Chemotherapy and Their Oncologist's Awareness of These Preferences.
AB  - Communication about palliative treatment options requires a balance between
      providing patients with sufficient information and not providing unwanted
      information. Surveys have indicated that many patients with advanced cancer
      express a wish to receive detailed information. In this prospective multicenter
      study, the information desire of patients with advanced breast or colorectal
      cancer was further investigated by offering treatment-related information to
      patients using a decision aid (DA). In addition, this study explored oncologists'
      awareness of their patients' information desire. Seventy-seven patients with
      advanced breast or colorectal cancer facing the decision whether to start second
      line palliative chemotherapy were offered a DA by a nurse. This DA contained
      information on adverse events, tumor response, and survival. The nurse asked the
      patient whether each information item was desired. Ninety-five percent of
      patients chose to receive information on adverse events, 91 % chose to receive
      information on tumor response, and 74 % chose to receive information on survival.
      Oncologists' judgment of patients' information desire was 100, 97, and 81 %,
      respectively. For all three information items together, oncologists correctly
      judged the information desire of 62 % of patients. This study confirms that many
      patients with advanced cancer wish to receive detailed information on the
      benefits and risks of palliative treatment options when the information is
      actually available. Oncologists were adequately aware of this high information
      desire, but had some difficulty judging the information desire of individual
      patients. A stepped approach to giving information ("preview, ask, tell, ask")
      may help to better meet patients' information needs.

PMID- 25985962
TI  - Authors' response.

PMID- 25985961
TI  - Evaluation of a Culturally Tailored Education to Promote Breast and Cervical
      Cancer Screening Among Chinese-Australian Women.
AB  - This paper aims to evaluate the impact of the culturally sensitive and
      linguistically appropriate education program on the following: (i) awareness of
      screening practices (breast awareness, mammogram, and Pap smear test); (ii)
      screening intention within the next six months; and (iii) knowledge about breast
      and cervical cancer among Chinese-Australian women. Titled "Happy and Healthy
      Life in Sydney," this was a quasi-experimental study with both pre- and post-test
      design. A convenience sample of 288 Chinese women was recruited through Chinese
      organizations such as churches and community centers. Participants completed the
      questionnaires before and after the educational program. The results show that
      the program was effective in promoting awareness of breast and cervical cancer
      screening and resulted in increased participative intentions in both mammogram
      and Pap smear testing within the next 6 months. Results also indicate that
      knowledge and belief scores were significantly increased. CONCLUSION: Our study
      supports that educational programs which use culturally sensitive and
      linguistically appropriate strategies are effective in improving both knowledge
      of breast and cervical cancer and awareness of their early detection practices
      among Chinese-Australian women.

PMID- 25985963
TI  - Erratum to: Efficacy of cleaning tablets for removable orthodontic appliances. An
      in vivo pilot study.

PMID- 25985964
TI  - Erratum to: Skeletal anchorage for everybody? A questionnaire study on frequency
      of use and clinical indications in daily practice.

PMID- 25985965
TI  - Hybrid PET/MR imaging: physics and technical considerations.
AB  - In just over a decade, hybrid imaging with FDG PET/CT has become a standard
      bearer in the management of cancer patients. An exquisitely sensitive whole-body
      imaging modality, it combines the ability to detect subtle biologic changes with
      FDG PET and the anatomic information offered by CT scans. With advances in MR
      technology and advent of novel targeted PET radiotracers, hybrid PET/MRI is an
      evolutionary technique that is poised to revolutionize hybrid imaging. It offers
      unparalleled spatial resolution and functional multi-parametric data combined
      with biologic information in the non-invasive detection and characterization of
      diseases, without the deleterious effects of ionizing radiation. This article
      reviews the basic principles of FDG PET and MR imaging, discusses the salient
      technical developments of hybrid PET/MR systems, and provides an introduction to
      FDG PET/MR image acquisition. 

PMID- 25985966
TI  - Practical guide for implementing hybrid PET/MR clinical service: lessons learned
      from our experience.
AB  - Positron emission tomography (PET) and magnetic resonance imaging, until
      recently, have been performed on separate PET and MR systems with varying
      temporal delay between the two acquisitions. The interpretation of these two
      separately acquired studies requires cognitive fusion by radiologists/nuclear
      medicine physicians or dedicated and challenging post-processing. Recent advances
      in hardware and software with introduction of hybrid PET/MR systems have made it
      possible to acquire the PET and MR images simultaneously or near simultaneously.
      This review article serves as a road-map for clinical implementation of hybrid
      PET/MR systems and briefly discusses hardware systems, the personnel needs,
      safety and quality issues, and reimbursement topics based on experience at NYU
      Langone Medical Center and Cleveland Clinic. 

PMID- 25985967
TI  - Introduction to the special section on small bowel imaging.

PMID- 25985968
TI  - Simultaneous Multislice Accelerated Free-Breathing Diffusion-Weighted Imaging of
      the Liver at 3T.
AB  - PURPOSE: To perform image quality comparison between accelerated multiband
      diffusion acquisition (mb2-DWI) and conventional diffusion acquisition (c-DWI) in
      patients undergoing clinically indicated liver MRI. METHODS: In this prospective
      study 22 consecutive patients undergoing clinically indicated liver MRI on a 3-T
      scanner equipped to perform multiband diffusion-weighed imaging (mb-DWI) were
      included. DWI was performed with single-shot spin-echo echo-planar technique with
      fat-suppression in free breathing with matching parameters when possible using c
      DWI, mb-DWI, and multiband DWI with a twofold acceleration (mb2-DWI). These
      diffusion sequences were compared with respect to various parameters of image
      quality, lesion detectability, and liver ADC measurements. RESULTS: Accelerated
      mb2-DWI was 40.9% faster than c-DWI (88 vs. 149 s). Various image quality
      parameter scores were similar or higher on mb2-DWI when compared to c-DWI. The
      overall image quality score (averaged over the three readers) was significantly
      higher for mb-2 compared to c-DWI for b = 0 s/mm(2) (3.48 +/- 0.52 vs. 3.21 +/-
      0.54; p = 0.001) and for b = 800 s/mm(2) (3.24 +/- 0.76 vs. 3.06 +/- 0.86; p =
      0.010). Total of 25 hepatic lesions were visible on mb2-DWI and c-DWI, with
      identical lesion detectability. There was no significant difference in liver ADC
      between mb2-DWI and c-DWI (p = 0.12). Bland-Altman plot demonstrates lower mean
      liver ADC with mb2-DWI compared to c-DWI (by 0.043 * 10(-3) mm(2)/s or 3.7% of
      the average ADC). CONCLUSION: Multiband technique can be used to increase
      acquisition speed nearly twofold for free-breathing DWI of the liver with similar
      or improved overall image quality and similar lesion detectability compared to
      conventional DWI.

PMID- 25985969
TI  - Spectrum of abdominal imaging findings in histiocytic disorders.
AB  - OBJECTIVES: The present article provides an overview of the spectrum of abdominal
      findings of histiocytic disorders that may be observed in multimodality imaging
      illustrated by clinical cases from our Imaging Center. METHODS: We will review
      abdominal findings of Langerhans cell histiocytosis, Rosai-Dorfman disease,
      Erdheim-Chester disease, and hemophagocytic syndrome illustrated by clinical
      cases from our imaging department with histologic correlation. RESULTS: Abdominal
      involvement of histiocytic disorders is rare and may occur in the liver, biliary
      tract, kidney, retroperitoneum, kidney, gastrointestinal tract, and lymph nodes.
      CONCLUSION: Histiocytic disorders encompass a group of rare diseases with a wide
      range of manifestations in which the abdominal involvement is quite infrequent.
      The role of the radiologist is to report the major imaging findings and the
      differential diagnosis; however, the imaging features are unspecific and biopsy
      usually is necessary to establish the definitive diagnosis.

PMID- 25985970
TI  - The response of trypanosomes and other eukaryotes to ER stress and the spliced
      leader RNA silencing (SLS) pathway in Trypanosoma brucei.
AB  - The unfolded protein response (UPR) is induced when the quality control machinery
      of the cell is overloaded with unfolded proteins or when one of the functions of
      the endoplasmic reticulum (ER) is perturbed. Here, I describe UPR in yeast and
      mammals, and compare it to what we know about pathogenic fungi and the parasitic
      protozoans from the order kinetoplastida, focusing on the novel pathway the
      spliced leader silencing (SLS) in Trypanosoma brucei. Trypanosomes lack
      conventional transcription regulation, and thus, lack most of the UPR machinery
      present in other eukaryotes. Trypanosome genes are transcribed in polycistronic
      units that are processed by trans-splicing and polyadenylation. In trans
      splicing, which is essential for processing of each mRNA, an exon known as the
      spliced leader (SL) is added to all mRNAs from a small RNA, the SL RNA. Under
      severe ER stress, T. brucei elicits the SLS pathway. In SLS, the transcription of
      the SL RNA gene is extinguished, and the entire transcription complex dissociates
      from the SL RNA promoter. Induction of SLS is mediated by an ER-associated kinase
      (PK3) that migrates to the nucleus, where it phosphorylates the TATA-binding
      protein (TRF4), leading shut-off of SL RNA transcription. As a result, trans
      splicing is inhibited and the parasites activate a programmed cell death (PCD)
      pathway. Despite the ability to sense the ER stress, the different eukaryotes,
      especially unicellular parasites and pathogenic fungi, developed a variety of
      unique and different ways to sense and adjust to this stress in a manner
      different from their host. 

PMID- 25985971
TI  - Activated human B cells induce inflammatory fibroblasts with cartilage
      destructive properties and become functionally suppressed in return.
AB  - BACKGROUND: Cross-talk between synovial fibroblasts (SF) and immune cells is
      suggested to play a crucial role in inflammation and chronification of rheumatoid
      arthritis (RA). The contribution of B cells in this process is poorly defined.
      METHODS: Here, primary B cells from healthy donors were polyclonally activated
      and cocultured with SF of non-synovitic origin from patients with osteoarthritis.
      RESULTS: In B-SF cocultures the concentrations of interleukin 6 (IL-6) and IL-8
      increased manifold compared with single cultures even under physical separation
      and remained stable for several days after B-cell removal. Intracellular staining
      confirmed SF as key producers of IL-6 and IL-8, and B cells as main producers of
      tumour necrosis factor alpha (TNFalpha) and IL-1beta. Blocking experiments with a
      combination of anti-TNFalpha-antibodies and rIL-1RA significantly reduced SF
      cytokine production by up to 90%, suggesting that B-cell-derived TNFalpha and IL
      1beta were crucial mediators of SF activation. Interestingly, B-cell cytokine
      production, CD25 expression and proliferation decreased in cocultures by at least
      50%, demonstrating a negative regulatory loop towards the activated B cells.
      Inhibition of activin receptor-like kinase 5, a crucial component of the tumour
      growth factor beta (TGFbeta) signalling pathway, partly restored B-cell
      proliferation, suggesting a contribution of SF-derived TGFbeta in B-cell
      suppression. Besides cytokines, B-cell-activated SF also upregulated secretion of
      matrix metalloproteases such as MMP-3, thereby acquiring potential tissue
      destructive properties. This was confirmed by their invasion into human cartilage
      in the severe combined immunodeficiency mouse fibroblast invasion model in vivo.
      CONCLUSIONS: Interaction with activated B cells leads to conversion of non
      arthritic SF into SF with a proinflammatory and aggressive RA-like phenotype,
      thereby suggesting a new, so far unrecognised role for B cells in RA
      pathogenesis.

PMID- 25985973
TI  - The implementation of a municipal indoor ice skating helmet policy: effects on
      helmet use, participation and attitudes.
AB  - RELEVANT LOCAL INJURY EPIDEMIOLOGY: In Ottawa, between 2005 and 2009 there was an
      annual average of 47.2 head injuries due to ice skating in children and youth (1
      19 years of age) requiring a visit to the emergency department, with the highest
      rates among those aged 5-14 years. Between 2002 and 2007, only 6% of children
      were wearing a helmet during ice skating when the head injury occurred. During
      indoor public skating sessions, 93% of children (<10 years)-57% aged 10-12 years,
      20% aged 13-17 years and 9% adults-wore helmets in the absence of a policy.
      Support for a helmet policy was high from public health, medical, political and
      community perspectives. BEST PRACTICE: Helmet policies in relation to cycling
      have demonstrated increases in helmet use and reduction of head injuries without
      decreasing physical activity. However, no known studies have examined the effect
      of indoor ice skating helmet policy coupled with education and promotional
      activities on helmet use, participation and attitudes towards helmet use.
      IMPLEMENTATION: An ice skating helmet policy for children (<11 years of age) and
      those with limited skating experience at indoor rinks during public skating
      sessions was developed, implemented and evaluated. Supportive activities such as
      discount coupons, promotional materials, a media launch, social marketing and
      staff training are described. DISCUSSION: The helmet policy was associated with
      increased helmet use for young children and for older children, youth and adults
      not included in the policy, without decreasing attendance to public skating
      sessions.

PMID- 25985972
TI  - The risk and nature of flares in juvenile idiopathic arthritis: results from the
      ReACCh-Out cohort.
AB  - OBJECTIVE: To describe probabilities and characteristics of disease flares in
      children with juvenile idiopathic arthritis (JIA) and to identify clinical
      features associated with an increased risk of flare. METHODS: We studied children
      in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh
      Out) prospective inception cohort. A flare was defined as a recurrence of disease
      manifestations after attaining inactive disease and was called significant if it
      required intensification of treatment. Probability of first flare was calculated
      with Kaplan-Meier methods, and associated features were identified using Cox
      regression. RESULTS: 1146 children were followed up a median of 24 months after
      attaining inactive disease. We observed 627 first flares (54.7% of patients) with
      median active joint count of 1, physician global assessment (PGA) of 12 mm and
      duration of 27 weeks. Within a year after attaining inactive disease, the
      probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24%
      to 30%) for a significant flare. Within a year after stopping treatment, it was
      31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm,
      maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis,
      antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs
      (DMARDs) or biological agents before attaining inactive disease were associated
      with increased risk of flare. Systemic JIA was associated with the lowest risk of
      flare. CONCLUSIONS: In this real-practice JIA cohort, flares were frequent,
      usually involved a few swollen joints for an average of 6 months and 60% led to
      treatment intensification. Children with a severe disease course had an increased
      risk of flare.

PMID- 25985974
TI  - Validation of ICDPIC software injury severity scores using a large regional
      trauma registry.
AB  - BACKGROUND: Administrative or quality improvement registries may or may not
      contain the elements needed for investigations by trauma researchers.
      International Classification of Diseases Program for Injury Categorisation
      (ICDPIC), a statistical program available through Stata, is a powerful tool that
      can extract injury severity scores from ICD-9-CM codes. We conducted a validation
      study for use of the ICDPIC in trauma research. METHODS: We conducted a
      retrospective cohort validation study of 40,418 patients with injury using a
      large regional trauma registry. ICDPIC-generated AIS scores for each body region
      were compared with trauma registry AIS scores (gold standard) in adult and
      paediatric populations. A separate analysis was conducted among patients with
      traumatic brain injury (TBI) comparing the ICDPIC tool with ICD-9-CM embedded
      severity codes. Performance in characterising overall injury severity, by the
      ISS, was also assessed. RESULTS: The ICDPIC tool generated substantial
      correlations in thoracic and abdominal trauma (weighted kappa 0.87-0.92), and in
      head and neck trauma (weighted kappa 0.76-0.83). The ICDPIC tool captured TBI
      severity better than ICD-9-CM code embedded severity and offered the advantage of
      generating a severity value for every patient (rather than having missing data).
      Its ability to produce an accurate severity score was consistent within each body
      region as well as overall. CONCLUSIONS: The ICDPIC tool performs well in
      classifying injury severity and is superior to ICD-9-CM embedded severity for
      TBI. Use of ICDPIC demonstrates substantial efficiency and may be a preferred
      tool in determining injury severity for large trauma datasets, provided
      researchers understand its limitations and take caution when examining smaller
      trauma datasets.

PMID- 25985975
TI  - Whom Do Migrant Home Care Workers Contact in the Case of Work-Related Abuse? An
      Exploratory Study of Help-Seeking Behaviors.
AB  - Migrant home care workers constitute an "invisible" and vulnerable group in
      society, as they work in isolation in the homes of frail older adults. Past
      research has shown that this population is particularly vulnerable to work
      related abuse. The aim of the present study was to explore the help-seeking
      behaviors of migrant home care workers who were exposed to work-related abuse.
      Overall, 187 Filipino home care workers completed a self-report questionnaire
      regarding four types of work-related abuse (sexual, physical, emotional, and
      exploitation), help-seeking strategies (i.e., formal and informal reporting), and
      reasons for not disclosing abusive incidents. A total of 56.7% reported some type
      of abuse. Of these, less than half reported the abuse, mostly informally to
      family and friends. None reported the abuse to the police. Main reasons for not
      disclosing the abuse were fears that things would get worse and the belief that
      it will take too much time and effort. The findings demonstrate that migrant home
      care workers are highly vulnerable to work-related abuse but are not likely to
      report work-related abuse and put an end to the cycle of abuse and violence. This
      calls for the development of further policy and interventions to protect this
      already vulnerable population.

PMID- 25985976
TI  - The View From the Bottom: Relative Deprivation and Bullying Victimization in
      Canadian Adolescents.
AB  - We investigated the relation between relative deprivation (RD)-disparity in
      affluence between adolescents and their more affluent schoolmates-and involvement
      in bullying among 23,383 students (aged 9-19) in 413 schools that participated in
      the 2010 Canadian Health Behavior in School-Aged Children survey. Students
      reported family affluence and frequency of bullying victimization and
      perpetration during the previous 2 months. Using the Yitzhaki index of RD and
      multinomial logistic regression analysis, we found that RD positively related to
      three types of bullying victimization (physical, relational, and cyberbullying)
      and to two types of perpetration (relational and cyberbullying) after differences
      in absolute affluence were held constant. These findings suggest that RD uniquely
      contributes to risk of bullying involvement.

PMID- 25985977
TI  - A phase 1 safety study of veliparib combined with cisplatin and etoposide in
      extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research
      Group (E2511).
AB  - OBJECTIVES: Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and
      etoposide (E) in preclinical models of SCLC. We conducted this phase 1 study to
      establish the safety of the combination in human subjects. MATERIALS AND METHODS:
      The study employed the 3+3 dose escalation design to establish the safety and
      recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75
      mg/m(2) on day 1) and E (100mg/m(2) on days 1-3) in a 21-day cycle. The starting
      dose of V was 60 mg (bid days 1-7) with plan to escalate to 100mg (days 1-7) or
      de-escalate to 40 mg (days 1-7) depending on the dose limiting toxicity (DLT)
      experience during cycle 1. Patients with treatment-naive, extensive stage SCLC
      were included. RESULTS: The study enrolled 9 patients: M/F (4/5); median age
      (60); White/African American (8/1). V was tolerated at the 60 mg (DLT in 0 of 3
      patients) and 100mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure).
      Veliparib at 100mg in combination with standard doses of C and E was established
      as the RP2D. Grades 3-5 adverse events irrespective of attribution during cycle 1
      included: dehydration (1), diarrhea (1), fatigue (1), febrile neutropenia (1),
      heart failure (1), leukopenia (6), lymphopenia (1), nausea (2), neutropenia (8),
      respiratory failure (1), and thrombocytopenia (2). Investigator-assessed efficacy
      outcome in 7 evaluable patients were stable disease in 2/7 (28.6%), partial
      response in 4/7 (57.1%), and complete response in 1/7 (14.3%) patients.
      CONCLUSIONS: This study demonstrated the safety of combining veliparib with
      cisplatin and etoposide in previously untreated SCLC patients.

PMID- 25985980
TI  - Nonalcoholic Wernicke's encephalopathy.
AB  - Wernicke's encephalopathy (WE) is a serious neurologic condition resulting from
      thiamine deficiency. The majority of cases involve alcoholism; however,
      nonalcohol-associated WE does occur and is under-recognized. We discuss a case of
      a 22-year-old man with a history of Crohn's disease who presented to our
      emergency department with multiple neurologic complaints related to WE. 

PMID- 25985978
TI  - Reinforcement and Stimulant Medication Ameliorate Deficient Response Inhibition
      in Children with Attention-Deficit/Hyperactivity Disorder.
AB  - This study examined the degree to which reinforcement, stimulant medication, and
      their combination impact response inhibition in children with Attention
      Deficit/Hyperactivity Disorder (ADHD). Across three studies, participants with
      ADHD (n = 111, 25 girls) and typically-developing (TD) controls (n = 33, 6 girls)
      completed a standard version of the stop signal task (SST) and/or a reinforcement
      manipulation SST with performance-contingent points. In two of these studies,
      these tasks were performed under placebo or 0.3 and 0.6 mg/kg methylphenidate
      (MPH) conditions. Cross-study comparisons were conducted to test hypotheses
      regarding the separate and combined effects of reinforcement and methylphenidate
      on response inhibition among children with ADHD relative to TD controls. Baseline
      response inhibition was worse among children with ADHD compared to controls. MPH
      produced dose-related improvements in response inhibition in children with ADHD;
      compared to non-medicated TD controls, 0.3 mg/kg MPH normalized deficient
      response inhibition, and 0.6 mg/kg MPH resulted in better inhibition in children
      with ADHD. Reinforcement improved response inhibition to a greater extent for
      children with ADHD than for TD children, normalizing response inhibition. The
      combination of MPH and reinforcement improved response inhibition among children
      with ADHD compared to reinforcement alone and MPH alone, also resulting in
      normalization of response inhibition despite repeated task exposure. Deficient
      response inhibition commonly observed in children with ADHD is significantly
      improved with MPH and/or reinforcement, normalizing inhibition relative to TD
      children tested under standard conditions.

PMID- 25985979
TI  - Response Inhibition, Peer Preference and Victimization, and Self-Harm:
      Longitudinal Associations in Young Adult Women with and without ADHD.
AB  - Self-harm (suicidal ideation and attempts; non-suicidal self-injuries behavior)
      peaks in adolescence and early-adulthood, with rates higher for women than men.
      Young women with childhood psychiatric diagnoses appear to be at particular risk,
      yet more remains to be learned about the key predictors or mediators of self-harm
      outcomes. Our aims were to examine, with respect to self-harm-related outcomes in
      early adulthood, the predictive validity of childhood response inhibition, a
      cardinal trait of attention-deficit hyperactivity disorder (ADHD), as well as the
      potential mediating effects of social preference and peer victimization,
      ascertained in early adolescence. Participants were an ethnically and
      socioeconomically diverse sample of 228 girls with and without ADHD, an enriched
      sample for deficits in response inhibition. Childhood response inhibition (RI)
      predicted young-adult suicide ideation (SI), suicide attempts (SA), and non
      suicidal self-injury (NSSI), over and above full-scale IQ, mother's education,
      household income, and age. Importantly, teacher-rated social preference in
      adolescence was a partial mediator of the RI-SI/SA linkages; self-reported peer
      victimization in adolescence emerged as a significant partial mediator of the RI
      NSSI linkage. We discuss implications for conceptual models of self-harm and for
      needed clinical services designed to detect and reduce self-harm.

PMID- 25985982
TI  - Ventilatory abnormalities in patients with cystic fibrosis undergoing the
      submaximal treadmill exercise test.
AB  - BACKGROUND: Exercise has been studied as a prognostic marker for patients with
      cystic fibrosis (CF), as well as a tool for improving their quality of life and
      analyzing lung disease. In this context, the aim of the present study was to
      evaluate and compare variables of lung functioning. Our data included: (i)
      volumetric capnography (VCAP) parameters: expiratory minute volume (VE), volume
      of exhaled carbon dioxide (VCO2), VE/VCO2, ratio of dead space to tidal volume
      (VD/VT), and end-tidal carbon dioxide (PetCO2); (ii) spirometry parameters:
      forced vital capacity (FVC), percent forced expiratory volume in the first second
      of the FVC (FEV1%), and FEV1/FVC%; and (iii) cardiorespiratory parameters: heart
      rate (HR), respiratory rate, oxygen saturation (SpO2), and Borg scale rating at
      rest and during exercise. The subjects comprised children, adolescents, and young
      adults aged 6-25 years with CF (CF group [CFG]) and without CF (control group
      [CG]). METHODS: This was a clinical, prospective, controlled study involving 128
      male and female patients (64 with CF) of a university hospital. All patients
      underwent treadmill exercise tests and provided informed consent after study
      approval by the institutional ethics committee. Linear regression, Kruskal-Wallis
      test, and Mann-Whitney test were performed to compare the CFG and CG. The alpha
      value was set at 0.05. RESULTS: Patients in the CFG showed significantly
      different VCAP values and spirometry variables throughout the exercise test.
      Before, during, and after exercise, several variables were different between the
      two groups; statistically significant differences were seen in the spirometry
      parameters, SpO2, HR, VCO2, VE/VCO2, PetCO2, and Borg scale rating. VCAP
      variables changed at each time point analyzed during the exercise test in both
      groups. CONCLUSION: VCAP can be used to analyze ventilatory parameters during
      exercise. All cardiorespiratory, spirometry, and VCAP variables differed between
      patients in the CFG and CG before, during, and after exercise.

PMID- 25985981
TI  - Transdentinal cytotoxicity of glutaraldehyde on odontoblast-like cells.
AB  - OBJECTIVES: This study investigated the transdentinal cytotoxicity of
      glutahaldehyde-containing solutions/materials on odontoblast-like cells. METHODS:
      Dentin discs were adapted to artificial pulp chambers. MDPC-23 cells were seeded
      on the pulpal side of the discs and the occlusal surface was treated with the
      following solutions: water, 2% glutaraldehyde (GA), 5% GA, 10% GA, Gluma Comfort
      Bond+Desensitizer (GCB+De) or Gluma Desensitizer (GDe). Cell viability and
      morphology were assessed by the Alamar Blue assay and SEM. The eluates were
      collected and applied on cells seeded in 24-well plates. After 7 or 14 days the
      total protein (TP) production, alkaline phosphatase activity (ALP) and deposition
      of mineralized nodules (MN) were evaluated. RESULTS: Data were analyzed by
      Kruskal-Wallis and Mann-Whitney tests (p<0.05). GA solutions were not cytotoxic
      against MDPC-23. GCB+De (85.1%) and GDe (77.2%) reduced cell viability as well as
      TP production and ALP activity at both periods. After 14 days, GCB+De and GDe
      groups produced less MN. Affected MDPC-23 presented deformation of the
      cytoskeleton and reduction of cellular projections. CONCLUSIONS: The treatment
      with 2.5%, 5% and 10% GA was not harmful to odontoblast-like cells. Conversely,
      when GA was combined with other components like HEMA, the final material became
      cytotoxic. CLINICAL SIGNIFICANCE: Glutaraldehyde has been used to decrease dentin
      hypersensitivity. This substance is also capable of preventing resin-dentin bond
      degradation by cross-linking collagen and MMPs. This study showed that GA might
      be safe when applied on acid etched dentin. However, when combined with HEMA the
      product becomes cytotoxic.

PMID- 25985983
TI  - Identification of functional candidates amongst hypothetical proteins of
      Mycobacterium leprae Br4923, a causative agent of leprosy.
AB  - Mycobacterium leprae is an intracellular obligate parasite that causes leprosy in
      humans, and it leads to the destruction of peripheral nerves and skin
      deformation. Here, we report an extensive analysis of the hypothetical proteins
      (HPs) from M. leprae strain Br4923, assigning their functions to better
      understand the mechanism of pathogenesis and to search for potential therapeutic
      interventions. The genome of M. leprae encodes 1604 proteins, of which the
      functions of 632 are not known (HPs). In this paper, we predicted the probable
      functions of 312 HPs. First, we classified all HPs into families and subfamilies
      on the basis of sequence similarity, followed by domain assignment, which
      provides many clues for their possible function. However, the functions of 320
      proteins were not predicted because of low sequence similarity with proteins of
      known function. Annotated HPs were categorized into enzymes, binding proteins,
      transporters, and proteins involved in cellular processes. We found several novel
      proteins whose functions were unknown for M. leprae. These proteins have a
      requisite association with bacterial virulence and pathogenicity. Finally, our
      sequence-based analysis will be helpful for further validation and the search for
      potential drug targets while developing effective drugs to cure leprosy. 

PMID- 25985984
TI  - Alexander disease in a dog: case presentation of electrodiagnostic, magnetic
      resonance imaging and histopathologic findings with review of literature.
AB  - BACKGROUND: Alexander disease is a rare neurodegenerative disorder that has not
      often been described in dogs. None of the existing descriptions include
      electrodiagnostic or magnetic resonance imaging workup. This is the first
      presentation of the results of an electrodiagnostic evaluation including
      electromyography, motor nerve conduction velocity, F-wave, the brainstem auditory
      evoked response and magnetic resonance imaging of a dog with Alexander disease.
      CASE PRESENTATION: A six month old male entire Bernese mountain dog was presented
      with central nervous system symptoms of generalized tremor, general stiffness,
      decreased proprioceptive positioning, a reduced menace response, decreased
      physiological nystagmus, myotonic spasms and increased spinal reflexes which
      progressed to lateral recumbency. The electromyography revealed normal muscle
      activity and a decreased motor nerve conduction velocity, temporal dispersion of
      the compound muscle action potential, prolonged F-wave minimal latency, lowered F
      ratio, decreased latency, and lowered amplitude of the brainstem auditory evoked
      potentials. The magnetic resonance imaging examination revealed ventriculomegaly
      and linear hyperintensity on the border of the cortical grey and white matter.
      The histopathological examination confirmed the presence of diffuse degenerative
      changes of the white matter throughout the neuraxis. A proliferation of abnormal
      astrocytes was found at the border between the white matter and cortex. There was
      also a massive accumulation of eosinophilic Rosenthal fibers as well as diffuse
      proliferation of abnormally large astrocytes and unaffected neurons. CONCLUSION:
      This is the first histopathologically confirmed case of Alexander disease in a
      dog with a full neurological workup. The results of the electrodiagnostic and
      magnetic resonance imaging examinations allow for a high-probability antemortem
      diagnosis of this neurodegenerative disorder in dogs.

PMID- 25985986
TI  - Development of a Dual Path Platform (DPP(r)) immunoassay for rapid detection of
      Candida albicans in human whole blood and serum.
AB  - Candida albicans is an opportunistic pathogen which can lead to Candidiasis and
      blood-stream infections, resulting in a mortality rate near 40%. Given its high
      fatality and emerging pathogenicity, there is a strong need for the development
      of a rapid C. albicans diagnostic assay. Point-of-care devices, specifically
      lateral flow assays, are an attractive and often employed diagnostic modality for
      C. albicans detection. However, they lack the required performance
      characteristics needed for accurate pathogen detection and subsequent treatment
      options. Thus, we describe herein the utility of the Dual Path Platform (DPP(r))
      device as an immunochromatographic Point-of-care assay for C. albicans. The limit
      of detection for hyphal and budding C. albicans in DPP(r) tests are reported to
      be as low as 7.94 * 10(5) whole cells/mL in human serum. C. albicans cells were
      detected with up to a 3.9 fold increase in sensitivity on DPP(r) when compared to
      conventional lateral flow modalities.

PMID- 25985985
TI  - Application of salivary antibody immunoassays for the detection of incident
      infections with Norwalk virus in a group of volunteers.
AB  - Norovirus infection is the most common cause of acute gastroenteritis in
      developed countries. Developing an assay based on a non-invasive biomarker for
      detecting incident norovirus infections could improve disease surveillance and
      epidemiological investigations. This project involved analysis of IgA and IgG
      norovirus-specific antibody responses in saliva samples from a Norwalk virus
      (Genogroup I, genotype 1 norovirus) challenge study involving infected and
      symptomatic, and non-infected asymptomatic individuals. Saliva was collected at
      the challenge, and two weeks and 40 days post-challenge. Samples were analyzed
      using the Luminex fluorometric and Meso Scale Discovery (MSD)
      electrochemiluminescence immunoassays. Recombinant P domains of Norwalk virus
      capsid protein, as well as similar recombinant proteins of two genogroup II
      noroviruses (VA387 and VA207) were used as antigens. Immunoconversions were
      defined as >4-fold increase in antibody responses to the norovirus antigens.
      Various sample pre-treatment options, buffers, saliva dilution ratios, and data
      adjustment approaches to control for sample-to-sample variability in saliva
      composition were compared using the Luminex assay. The results suggest that
      adjusting responses to the norovirus antigens for responses to the protein
      purification tag, glutathione-S-transferase (GST), significantly improved the
      odds of producing a correct immunoconversion test result. IgG-based tests were
      more accurate compared to IgA-based tests. At optimal conditions, both Luminex
      and MSD assays for Norwalk-specific IgG antibodies correctly identified all
      infected and non-infected individuals. There was no evidence of cross-reactivity
      of anti-Norwalk virus antibodies with genogroup II noroviruses. These results
      suggest that salivary antibody responses can be used for the detection of
      incident infections with Norwalk virus in prospective surveys.

PMID- 25985987
TI  - Osteonecrosis of the femoral head: treatment with ancillary growth factors.
AB  - Osteonecrosis (ON) of the femoral head, also known as avascular necrosis (AVN) of
      the femoral head, is a progressive disease that predominantly affects younger
      patients. During early stage of ON, decompression of the femoral head has been
      commonly used to improve pain. The decompression has been augmented with
      nonvascularized or vascularized bone grafts, mesenchymal stems cells, and growth
      factors. The use of adjuvant growth factors to supplement the core decompression
      has mainly been limited to animal models in an attempt to regenerate the necrotic
      lesion of ON. Factors utilized include bone morphogenetic proteins, vascular
      endothelial growth factors, hepatocyte growth factors, fibroblast growth factors,
      granulocyte colony-stimulating factors, and stem cells factors. In animal models,
      the use of these factors has been shown to increase bone formation and
      angiogenesis. Although promising, the use of these growth factors and cell-based
      therapies clinically remains limited. 

PMID- 25985988
TI  - Childhood Maltreatment and Perinatal Mood and Anxiety Disorders: A Systematic
      Review.
AB  - Perinatal mood and anxiety disorders (PMADs) compromise maternal and child well
      being and may be influenced by traumatic experiences across the life course. A
      potent and common form of trauma is childhood maltreatment, but its specific
      impact on PMADs is not well understood. A systematic review was undertaken to
      synthesize empirical literature on the relationship between maternal histories of
      childhood maltreatment and PMADs. Of the 876 citations retrieved, 35 reports from
      a total of 26,239 participants met inclusion criteria, documenting substantial
      rates of childhood maltreatment and PMADs. Robust trends of association were
      observed between childhood maltreatment and perinatal depression, as well as post
      traumatic stress disorder, but findings for anxiety were less consistent.
      Examining multivariate results suggested that childhood maltreatment predicts
      PMADs above and beyond sociodemographic, psychiatric, perinatal, and psychosocial
      factors, but may also be partially mediated by variables such as later
      victimization and moderated by protective early relationships. Future research
      should test mediating and moderating pathways using prospective cohorts,
      expanding to cross-cultural settings and other disorder outcomes. Treatment and
      prevention of childhood maltreatment and its sequelae may help mitigate risk for
      perinatal psychopathology and its impact on maternal and child outcomes.

PMID- 25985989
TI  - Rethinking Compassion Fatigue Through the Lens of Professional Identity: The Case
      of Child-Protection Workers.
AB  - Compassion fatigue is currently the dominant model in work-related stress studies
      that explain the consequences of caring for others on child-protection workers.
      Based on a deterministic approach, this model excludes the role of cognition a
      priori and a posteriori in the understanding of the impact of caregiving or
      providing social support. By integrating the notion of professional identity,
      this article adds a subjective perspective to the compassion fatigue model
      allowing for the consideration of positive outcomes and takes into account the
      influence of stress caused by accountability. Mainly, it is argued that meanings
      derived from identity and given to situations may protect or accelerate the
      development of compassion fatigue or compassion satisfaction. To arrive at this
      proposition, the notions of compassion fatigue and identity theory are first
      reviewed. These concepts are then articulated around four work-related stressors
      specific to child-protection work. In light of this exercise, it is argued that
      professional identity serves as a subjective interpretative framework that guides
      the understanding of work-related situations. Therefore, compassion fatigue is
      not only a simple reaction to external stimuli. It is influenced by meanings
      given to the situation. Furthermore, professional identity modulates the impact
      of compassion fatigue on psychological well-being. Practice, policy, and research
      implications in light of these findings are also discussed.

PMID- 25985990
TI  - Sexual Risk Behaviors, Sexual Offenses, and Sexual Victimization Among Homeless
      Youth: A Systematic Review of Associations With Substance Use.
AB  - The use of substances among youth experiencing homelessness is an important issue
      in the context of addressing the developing burden of morbidities arising due to
      illness, injury, physical and mental health concerns, and low rates of health
      care utilization among this population group. Youth experiencing homelessness
      report engaging in and being victimized by various forms of sexual behavior. Of
      interest in this systematic review were published studies investigating substance
      use in its association with perpetration of sexual offenses, engagement in sexual
      risk behavior, or experience of sexual victimization among homeless youth. A
      systematic search of 12 psychology, health, and social science electronic
      databases was conducted. Search terms included "homeless*," "youth," "sex
      crimes," "sexual victimization," "survival sex," "rape," "drugs," and "substance
      abuse." Twenty-three studies were identified that met the inclusion criteria. No
      studies statistically examining substance use in its association with
      perpetrating sexual offenses were located. Findings showed substance use was
      generally associated with sexual risk behavior or sexual victimization; however,
      it remains unclear whether substance use precedes or follows these behaviors and
      experiences. It is possible substances are used by homeless youth as a means of
      coping with sexual risk behavior and victimization. Implications of the review
      findings in relation to prevention and intervention approaches aimed to decrease
      the incidence and severity of health concerns among homeless youth are discussed.

PMID- 25985991
TI  - Concordance analysis of methylation biomarkers detection in self-collected and
      physician-collected samples in cervical neoplasm.
AB  - BACKGROUND: Non-attendance at gynecological clinics is a major limitation of
      cervical cancer screening and self-collection of samples may improve this
      situation. Although HPV testing of self-collected vaginal samples is acceptable,
      the specificity is inadequate. The current focus is increasing self-collection of
      vaginal samples to minimize clinic visits. In this study, we analyzed the
      concordance and clinical performance of DNA methylation biomarker (PAX1, SOX1,
      and ZNF582) detection in self-collected vaginal samples and physician-collected
      cervical samples for the identification of cervical neoplasm. METHODS: We
      enrolled 136 cases with paired methylation data identified from abnormal Pap
      smears (n = 126) and normal controls (n = 10) regardless of HPV status at
      gynecological clinics. The study group comprised 37 cervical intraepithelial
      neoplasm I (CIN1), 23 cervical intraepithelial neoplasm II (CIN2), 16 cervical
      intraepithelial neoplasm III (CIN3), 30 carcinoma in situ (CIS), 13 squamous cell
      carcinomas (SCCs) and seven adenocarcinomas (ACs)/adenosquamous carcinomas
      (ASCs). PAX1, SOX1 and ZNF582 methylation in study samples was assessed by real
      time quantitative methylation-specific polymerase chain reaction analysis. We
      generated methylation index cutoff values for the detection of CIN3+ in physician
      collected cervical samples for analysis of the self-collected group. Concordance
      between the physician-collected and self-collected groups was evaluated by
      Cohen's Kappa. Sensitivity, specificity and area under curve (AUC) were
      calculated for detection of CIN3+ lesions. Finally, we produced an optimal cutoff
      value with the best sensitivity from the self-collected groups. RESULTS: We
      generated a methylation index cutoff value from physician-collected samples for
      detection of CIN3+. There were no significant differences in sensitivity,
      specificity of PAX1, SOX1 and ZNF582 between the self-collected and physician
      collected groups. The methylation status of all three genes in the normal control
      samples, and the CIN 1, CIN2, CIN3, CIS, ACs/ASCs and SCC samples showed
      reasonable to good concordance between the two groups (kappa = 0.443, 0.427, and
      0.609 for PAX1, SOX1, and ZNF582, respectively). In determining the optimal
      cutoff values from the self-collected group, ZNF582 showed the highest
      sensitivity (0.77; 95%CI, 0.65-0.87) using a cutoff value of 0.0204. CONCLUSIONS:
      Methylation biomarker analysis of the three genes for detection of CIN3+ lesions
      shows reasonable to good concordance between the self-collected and physician
      collected samples. Therefore, self-collection of samples could be adopted to
      decrease non-attendance and improve cervical screening.

PMID- 25985992
TI  - Costs and cost-effectiveness of a large-scale mass testing and treatment
      intervention for malaria in Southern Province, Zambia.
AB  - BACKGROUND: A cluster, randomized, control trial of three dry-season rounds of a
      mass testing and treatment intervention (MTAT) using rapid diagnostic tests
      (RDTs) and artemether-lumefantrine (AL) was conducted in four districts in
      Southern Province, Zambia. METHODS: Data were collected on the costs and
      logistics of the intervention and paired with effectiveness estimated from a
      community randomized control trial for the purpose of conducting a provider
      perspective cost-effectiveness analysis of MTAT vs no MTAT (Standard of Care).
      RESULTS: Dry-season MTAT in this setting did not reduce malaria transmission
      sufficiently to permit transition to a case-investigation strategy to then pursue
      malaria elimination, however, the intervention did substantially reduce malaria
      illness and was a highly cost-effective intervention for malaria burden reduction
      in this moderate transmission area. The cost per RDT administered was estimated
      to be USD4.39 (range: USD1.62-13.96) while the cost per AL treatment administered
      was estimated to be USD34.74 (range: USD3.87-3,835). The net cost per disability
      adjusted life year averted (incremental cost-effectiveness ratio) was estimated
      to be USD804. CONCLUSIONS: The intervention appears to be highly cost-effective
      relative to World Health Organization thresholds for malaria burden reduction in
      Zambia as compared to no MTAT. However, it was estimated that population-wide
      mass drug administration is likely to be more cost-effective for burden reduction
      and for transmission reduction compared to MTAT.

PMID- 25985993
TI  - Cytoplasm replacement following germinal vesicle transfer restores meiotic
      maturation and spindle assembly in meiotically arrested oocytes.
AB  - Both the cytoplasmic and nuclear compartments are essential for the acquisition
      of meiotic competence. This study assessed the role of the cytoplasm in meiosis
      resumption in meiotically arrested oocytes at the germinal vesicle (GV) stage.
      Mouse oocytes at GV stage were meiotically arrested with 3-isobutyl-1
      methylxanthine (IBMX). GV transfer was performed between IBMX-treated and non
      treated (control) mouse oocytes, and between control mouse and human GV oocytes.
      Extrusion of first polar body (PB) was examined as an indication of nuclear
      maturation. Meiotic spindle assembly and chromosome alignment were examined by
      immunostaining. Results indicated that oocytes arrested with IBMX for 24 and 48 h
      exhibited reduced ability for meiotic maturation and for extruding the first PB
      when compared with controls (P < 0.01). IBMX-treated oocytes reconstituted with
      cytoplasm, but not GV, of control oocytes restored the assembly of meiotic
      spindle and meiotic maturation. Mouse oocytes reconstituted with GV of human
      oocytes underwent meiosis similar to that observed in mice, but not humans.
      Additionally, human oocytes reconstituted by mouse GV underwent meiosis similar
      to that observed in humans, but not mice. These findings suggest that cytoplasm
      replacement by GV transfer could represent a potential therapeutic option for
      women who do not produce mature oocytes during IVF. 

PMID- 25985994
TI  - DNA double strand breaks in human spermatozoa can be predictive for assisted
      reproductive outcome.
AB  - Sperm DNA status has been reported to predict fertility outcomes in infertile
      men. The terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling
      test (TUNEL) is the most widely used method to evaluate this; however, its
      prognostic value is still debated. One hundred infertile men undergoing
      intracytoplasmic sperm injection (ICSI) and 61 fertile men were tested for sperm
      parameters, sex hormones and sperm DNA status by chromatin tests (acridine
      orange, aniline blue, decondensation) and by direct assays (TUNEL and
      phosphorylated histone H2AX-gammaH2AX). In both groups, the prognostic value of
      each parameter to predict assisted clinical pregnancy was compared. Sperm
      parameters (P < 0.05 or P < 0.01), FSH levels (P < 0.05) and DNA status (P < 0.05
      to P < 0.001) were significantly different in participants compared with
      controls. Among infertile men, 47 had positive and 53 had ICSI outcome. Both
      chromatin analysis and TUNEL test were unable to distinguish individuals who had
      successful outcomes from those who failed ICSI treatments. gammaH2AX percentage
      and gammaH2AX fragmentation index were significantly higher in sperm from non
      pregnant compared with pregnant couples (P < 0.05 and P < 0.01). gammaH2AX assay
      is more predictive of ICSI outcome than TUNEL in infertile couples with male
      factor infertility. 

PMID- 25985995
TI  - The clinical utility of next-generation sequencing for identifying chromosome
      disease syndromes in human embryos.
AB  - Next-generation sequencing is emerging as a reliable and accurate technology for
      pre-implantation genetic diagnosis (PGD) of aneuploidies and translocations. The
      aim of this study was to extend the clinical utility of copy number variation
      sequencing (CNV-Seq) to the detection of small pathogenic copy number variations
      (CNVs) associated with chromosome disease syndromes. In preliminary validation
      studies, CNV-Seq was highly sensitive and specific for detecting small CNV in
      whole-genome amplification products from three replicates of one and five cell
      samples, with a resolution in the order of 1-2 Mb. Importantly, the chromosome
      positions of all CNV were correctly mapped with copy numbers similar to those
      measured in matching genomic DNA samples. In seven clinical PGD cycles where
      results were obtained for 34 of 35 blastocysts, CNV-Seq identified 18 blastocysts
      with aneuploidies, one with an aneuploidy and a 4.98 Mb 5q35.2-qter deletion
      associated with Sotos syndrome, one with a 6.66 Mb 7p22.1-pter deletion
      associated with 7p terminal deletion syndrome and 14 with no detectable
      abnormalities that were suitable for transfer. On the basis of these findings,
      CNV-Seq displays the hallmarks of a comprehensive PGD technology for detection of
      aneuploidies and CNVs that are known to affect the development and health of
      patient's embryos. 

PMID- 25985996
TI  - To pill or not to pill in GnRH-antagonist cycles: the answer is in the data
      already!
AB  - The planning of IVF treatment by scheduling menstruation and hence initiation of
      ovarian stimulation using sex-steroid pre-treatment is commonly used. Pooling
      data from six randomized-controlled trials encompassing 1343 patients, with and
      without combined oral contraceptive pill pre-treatment, suggests that the ongoing
      pregnancy rate per randomized woman is significantly lower in patients with oral
      contraceptive pill pre-treatment (relative risk [RR]: 0.80, 95% confidence
      interval [CI]: 0.66-0.97; rate difference [RD]: -5%, 95% CI: -10% to -1%; fixed
      effects model). This finding remains remarkably robust in multiple sensitivity
      analyses: exclusion of a study on poor responders, exclusion of the three
      smallest studies or exclusion of studies with a pill-free interval of less than 5
      days, results in RR of 0.78 (95% CI: 0.64-0.94), 0.80 (95% CI: 0.65-0.98) and
      0.79, (95% CI: 0.64-0.99), respectively. Furthermore, the finding of a
      significant reduction in ongoing pregnancy rate is not inconsistent with other
      evidence from the literature. The potential benefit of using oral contraceptive
      pill pre-treatment for cycle planning should therefore be balanced against its
      detrimental effect. Further randomized studies should test whether an effect
      similar to the one observed after combined oral contraceptive pill usage exists
      after other sex steroid pre-treatment regimens. 

PMID- 25985997
TI  - Altered segregation pattern and numerical chromosome abnormalities interrelate in
      spermatozoa from Robertsonian translocation carriers.
AB  - The aim of this study was to assess whether there is a relationship between
      numerical chromosome abnormalities and certain segregation modes in spermatozoa
      from Robertsonian translocation carriers. A sequential fluorescence in-situ
      hybridization protocol based on two successive hybridization rounds was performed
      on sperm samples from one t(13;22) and ten t(13;14) carriers. Patient inclusion
      criteria included the presence of a positive interchromosomal effect (ICE). In
      the first round, numerical abnormalities for chromosomes 15/22, 18, 21, X and Y
      were analysed. In the second round, the segregation outcome of the rearranged
      chromosomes was evaluated in the numerically abnormal spermatozoa detected in the
      first round, as well as in randomly assessed spermatozoa. Aneuploid spermatozoa
      showed statistical differences in all segregation modes when compared with
      randomly assessed spermatozoa: alternate (50.7% versus 84.3%), adjacent (36.6%
      versus 14.6%) and 3:0 (10.2% versus 1%). Diploid/multiple disomic spermatozoa
      showed differences in alternate (3.7% versus 84.3%) and 3:0 (67.6% versus 1%). We
      concluded that in Robertsonian translocation carriers that exhibit ICE,
      numerically abnormal spermatozoa preferentially contain unbalanced segregation
      products. This might be explained by heterosynapsis acting as a rescue mechanism
      that would lead to aberrant recombination, which is a predisposing factor for non
      disjunction events. 

PMID- 25985998
TI  - Interventional oncology for liver and lung metastases from colorectal cancer: The
      current state of the art.
AB  - Interventional oncology is developing rapidly as a result of advances in imaging
      and medical devices. Although the treatments offered are recent and not yet fully
      validated in the guidelines, they allow non-invasive curative treatments to be
      offered to a growing number of patients. When it is used in a highly selected
      patients with less than three metastases under 2-3cm in size, percutaneous tumor
      ablation offers local efficacy similar to excision surgery with considerable
      sparing of the parenchyma, both for lung and liver metastases. Hepatic intra
      arterial therapies (chemotherapy, radioembolization, and chemoembolization) are
      now "salvage" methods after chemotherapy has failed and are being assessed in
      earlier lines of treatment. 

PMID- 25985999
TI  - Repeated episodes of spontaneous regression/progression of cervical
      adenocarcinoma after adjuvant chemoradiation therapy: a case report.
AB  - INTRODUCTION: Spontaneous regression of cancer is thought to be a rare event.
      Here, we report an extremely rare case of repeated episodes of spontaneous
      regression and progression of recurrent cervical adenocarcinoma. CASE
      PRESENTATION: We report here a case of a 56-year-old Japanese woman who was
      diagnosed with cervical adenocarcinoma. Her hilar and mediastinal lymph nodes
      were swollen 6 years after the initial diagnosis and subsequent treatment, and
      were found to be pathologically malignant by mediastinal biopsy. Then, without
      any treatment, the hilar and mediastinal lymph nodes spontaneously regressed with
      decreases in tumor size and serum tumor marker levels, as confirmed by a decrease
      in uptake of fluorodeoxyglucose during positron emission tomography-computed
      tomography. Subsequently, although there were repeated episodes of increase and
      decrease in her serum tumor marker levels and lymph node size, her activities of
      daily living were and are well preserved. CONCLUSIONS: While spontaneous
      regression of a malignant tumor is a rare event, our case is even rarer in that
      repeated episodes of spontaneous regression/progression of cervical
      adenocarcinoma occurred.

PMID- 25986000
TI  - Development of a Quantitative Real-Time RT-PCR Assay for the Detection of MAGE-A3
      Positive Tumors.
AB  - Melanoma antigen A3 (MAGE-A3) is a member of the MAGE family of tumor antigens
      and a relevant candidate for use in cancer immunotherapy. However, not all tumors
      express MAGE-A3, and closely related members of the MAGE family can be co
      expressed with MAGE-A3 in the same tumor. Therefore, in the frame of MAGE-A3
      clinical trials, it appeared necessary to evaluate tumors for MAGE-A3 expression
      with a highly specific quantitative assay to select patients who are eligible for
      anti-MAGE-A3 immunotherapy treatment. Herein, we describe the development and
      validation of a quantitative real-time RT-PCR (RT-qPCR) assay for the
      determination of MAGEA3 gene expression in tumor tissues. In the early phases of
      development, the designed primers and probe were not able to distinguish between
      MAGE-A3 and MAGE-A6. To ensure the specificity for MAGE-A3 over MAGE-A6, our
      strategy was to use a 5'-nuclease probe (or hydrolysis probe). The final assay
      was shown to be specific and linear within the analytical range, with an
      acceptable CV for repeatability and intermediate precision. When compared with a
      reference semiquantitative RT-PCR assay, the two methods were in good agreement,
      with only 4.23% of the samples giving discordant results. In conclusion, we have
      developed a MAGE-A3-specific RT-qPCR assay, compatible with a high-throughput
      setting for the estimation of MAGEA3 gene expression in present and future
      clinical trials. 

PMID- 25986001
TI  - Associations between active travel and weight, blood pressure and diabetes in six
      middle income countries: a cross-sectional study in older adults.
AB  - BACKGROUND: There is little published data on the potential health benefits of
      active travel in low and middle-income countries. This is despite increasing
      levels of adiposity being linked to increases in physical inactivity and non
      communicable diseases. This study will examine: (1) socio-demographic correlates
      of using active travel (walking or cycling for transport) among older adults in
      six populous middle-income countries (2) whether use of active travel is
      associated with adiposity, systolic blood pressure and self-reported diabetes in
      these countries. METHODS: Data are from the WHO Study on Global Ageing and Adult
      Health (SAGE) of China, India, Mexico, Ghana, Russia and South Africa with a
      total sample size of 40,477. Correlates of active travel (>=150 min/week) were
      examined using logistic regression. Logistic and linear regression analyses were
      used to examine health related outcomes according to three groups of active
      travel use per week. RESULTS: 46.4% of the sample undertook >=150 min of active
      travel per week (range South Africa: 21.9% Ghana: 57.8%). In pooled analyses
      those in wealthier households were less likely to meet this level of active
      travel (Adjusted Risk Ratio (ARR) 0.77, 95% Confidence Intervals 0.67; 0.88
      wealthiest fifth vs. poorest). Older people and women were also less likely to
      use active travel for >=150 min per week (ARR 0.71, 0.62; 0.80 those aged 70+
      years vs. 18-29 years old, ARR 0.82, 0.74; 0.91 women vs. men). In pooled fully
      adjusted analyses, high use of active travel was associated with lower risk of
      overweight (ARR 0.71, 0.59; 0.86), high waist-to-hip ratio (ARR 0.71, 0.61; 0.84)
      and lower BMI (-0.54 kg/m(2), -0.98;- 0.11). Moderate (31-209 min/week) and high
      use (>=210 min/week) of active travel was associated with lower waist
      circumference (-1.52 cm (-2.40; -0.65) and -2.16 cm (3.07; -1.26)), and lower
      systolic blood pressure (-1.63 mm/Hg (-3.19; -0.06) and -2.33 mm/Hg (-3.98; 
      0.69)). CONCLUSIONS: In middle-income countries use of active travel for >=150
      min per week is more common in lower socio-economic groups and appears to confer
      similar health benefits to those identified in high-income settings. Efforts to
      increase active travel levels should be integral to strategies to maintain
      healthy weight and reduce disease burden in these settings.

PMID- 25986003
TI  - Lack of a clinically significant impact of race on morbidity and mortality in
      abdominal surgery: an analysis of 186,466 patients from the American College of
      Surgeons National Surgical Quality Improvement Program database.
AB  - BACKGROUND: Poorer surgical outcomes in black compared with white patients have
      been reported, but it remains unclear if race independently predicts worse
      outcomes. We investigated if blacks have poorer outcomes than whites following
      abdominal surgery at quality-seeking hospitals. METHODS: Using the American
      College of Surgeons' National Surgical Quality Improvement Program database,
      patients who were black or white and underwent common abdominal surgery
      procedures were identified. A total of 19,326 (10%) blacks and 167,140 (90%)
      whites undergoing abdominal surgery were analyzed. Statistical analyses were
      performed using SPSS v20. RESULTS: Thirty-day mortality for blacks compared with
      whites was not statistically significant for any procedures reviewed (all P >
      .05). Thirty-day morbidity for blacks was slightly higher in appendectomy (P <
      .0001), small bowel resection (P < .0001), and partial colectomy (P < .0001).
      CONCLUSION: Black compared with white patients did not have increased mortality
      following abdominal surgery but had minor, clinically insignificant, increased
      morbidity in appendectomy, small bowel resection, and partial colectomy.

PMID- 25986002
TI  - Splenectomy and increased subsequent cancer risk: a nationwide population-based
      cohort study.
AB  - BACKGROUND: Splenectomy has been suggested to have an impact on immunological
      function, and subsequent development of cancer has been recognized as a possible
      adverse effect of splenectomy. This study evaluated the possible association
      between splenectomy and malignancy in Taiwan. METHODS: A cohort study consisted
      of including 2,603 patients with nontraumatic and 2,295 patients with traumatic
      splenectomy, and then randomly frequency matched with 4 participants without
      splenectomy. The Cox proportional hazard regression analysis was conducted to
      estimate the influence of splenectomy on cancer risk. RESULTS: Both nontraumatic
      and traumatic splenectomy had a significantly higher risk for overall cancer
      development (adjusted hazard ratios are 2.64 and 1.29 for nontraumatic and
      traumatic reasons, respectively). After adjusting for age, sex, and
      comorbidities, patients with splenectomy were associated with significantly
      higher risks for developing certain gastrointestinal tract cancers, other head
      and neck cancers, and hematological malignancies, and the phenomenon is more
      prominent in nontraumatic splenectomy group. CONCLUSION: This nationwide
      population-based study found that people with splenectomy have higher risks of
      developing overall cancer, as well as certain site-specific cancers, especially
      for patients with nontraumatic reasons.

PMID- 25986005
TI  - Interfacial sciences in unconventional petroleum production: from fundamentals to
      applications.
AB  - With the ever increasing demand for energy to meet the needs of growth in
      population and improvement in the living standards in particular in developing
      countries, the abundant unconventional oil reserves (about 70% of total world
      oil), such as heavy oil, oil/tar sands and shale oil, are playing an increasingly
      important role in securing global energy supply. Compared with the conventional
      reserves unconventional oil reserves are characterized by extremely high
      viscosity and density, combined with complex chemistry. As a result, petroleum
      production from unconventional oil reserves is much more difficult and costly
      with more serious environmental impacts. As a key underpinning science,
      understanding the interfacial phenomena involved in unconventional petroleum
      production, such as oil liberation from host rocks, oil-water emulsions and
      demulsification, is critical for developing novel processes to improve oil
      production while reducing GHG emission and other environmental impacts at a lower
      operating cost. In the past decade, significant efforts and advances have been
      made in applying the principles of interfacial sciences to better understand
      complex unconventional oil-systems, while many environmental and production
      challenges remain. In this critical review, the recent research findings and
      progress in the interfacial sciences related to unconventional petroleum
      production are critically reviewed. In particular, the chemistry of
      unconventional oils, liberation mechanisms of oil from host rocks and mechanisms
      of emulsion stability and destabilization in unconventional oil production
      systems are discussed in detail. This review also seeks to summarize the current
      state-of-the-art characterization techniques and brings forward the challenges
      and opportunities for future research in this important field of physical
      chemistry and petroleum. 

PMID- 25986004
TI  - Implementation of an audit with feedback knowledge translation intervention to
      promote medication error reporting in health care: a protocol.
AB  - BACKGROUND: Health professionals strive to deliver high-quality care in an
      inherently complex and error-prone environment. Underreporting of medical errors
      challenges attempts to understand causative factors and impedes efforts to
      implement preventive strategies. Audit with feedback is a knowledge translation
      strategy that has potential to modify health professionals' medical error
      reporting behaviour. However, evidence regarding which aspects of this complex,
      multi-dimensional intervention work best is lacking. The aims of the Safe
      Medication Audit Reporting Translation (SMART) study are to: 1. Implement and
      refine a reporting mechanism to feed audit data on medication errors back to
      nurses 2. Test the feedback reporting mechanism to determine its utility and
      effect 3. Identify characteristics of organisational context associated with
      error reporting in response to feedback METHODS/DESIGN: A quasi-experimental
      design, incorporating two pairs of matched wards at an acute care hospital, is
      used. Randomisation occurs at the ward level; one ward from each pair is
      randomised to receive the intervention. A key stakeholder reference group informs
      the design and delivery of the feedback intervention. Nurses on the intervention
      wards receive the feedback intervention (feedback of analysed audit data) on a
      quarterly basis for 12 months. Data for the feedback intervention come from
      medication documentation point-prevalence audits and weekly reports on routinely
      collected medication error data. Weekly reports on these data are obtained for
      the control wards. A controlled interrupted time series analysis is used to
      evaluate the effect of the feedback intervention. Self-report data are also
      collected from nurses on all four wards at baseline and at completion of the
      intervention to elicit their perceptions of the work context. Additionally,
      following each feedback cycle, nurses on the intervention wards are invited to
      complete a survey to evaluate the feedback and to establish their intentions to
      change their reporting behaviour. To assess sustainability of the intervention,
      at 6 months following completion of the intervention a point-prevalence chart
      audit is undertaken and a report of routinely collected medication errors for the
      previous 6 months is obtained. This intervention will have wider application for
      delivery of feedback to promote behaviour change for other areas of preventable
      error and adverse events.

PMID- 25986006
TI  - Blood glucose response to rescue dextrose in hypoglycemic, critically ill
      patients receiving an insulin infusion.
AB  - BACKGROUND: There is inadequate guidance for clinicians on selection of the
      optimal dextrose 50% (D50W) dose for hypoglycemia correction in critically ill
      patients. OBJECTIVE: The purpose of this study was to determine the blood glucose
      (BG) response to D50W in critically ill patients. METHODS: A retrospective
      analysis was conducted of critically ill patients who received D50W for
      hypoglycemia (BG < 70 mg/dL) while on an insulin infusion. The primary objective
      of this study was to determine the BG response to D50W. The relationship between
      participant characteristics and the dose-adjusted change in BG following D50W was
      analyzed using simple and multiple linear mixed-effects models. RESULTS: There
      were 470 hypoglycemic events (BG < 70 mg/dL) corrected with D50W. The overall
      median BG response was 4.0 (2.53, 6.08) mg/dL per gram of D50W administered.
      Administration of D50W per protocol resulted in 32 episodes of hyperglycemia (BG
      > 150 mg/dL), resulting in a 6.8% rate of overcorrection; 49% of hypoglycemic
      episodes (230/470) corrected to a BG >100 mg/dL. A multivariable GEE analysis
      showed a significantly higher BG response in participants with diabetes (0.002)
      but a lower response in those with recurrent hypoglycemia (P = 0.049). The
      response to D50W increased with increasinginsulin infusion rate (P = 0.022). Burn
      patients experienced a significantly larger BG response compared with cardiac,
      medical, neurosurgical, or surgical patients. CONCLUSIONS: The observed median
      effect of D50W on BG was approximately 4 mg/dL per gram of D50W administered.
      Application of these data may aid in rescue protocol development that may reduce
      glucose variability associated with hypoglycemic episodes and the correction.

PMID- 25986007
TI  - Low-dose 3-factor prothrombin complex concentrate for warfarin reversal prior to
      heart transplant.
AB  - BACKGROUND: Anticoagulation with warfarin is common in patients presenting for
      heart transplant. Prior to surgery, anticoagulation reversal is necessary to
      avoid significant intraoperative and perioperative bleeding complications.
      Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma
      (FFP); however, these therapies have significant limitations. An alternative to
      FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin
      reversal protocol prior to heart transplant was implemented using low-dose PCC at
      our institution. OBJECTIVE: To assess blood product use, effectiveness, and
      safety post-low-dose PCC administration in patients needing warfarin reversal
      prior to heart transplant compared with historical controls. METHODS: This was a
      single-center, retrospective cohort study. The PCC cohort included patients
      undergoing heart transplant presenting with an international normalized ratio
      >=1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product
      use was measured from postoperative day 0 to 2. RESULTS: The PCC and historical
      control cohorts included 16 and 50 patients, respectively. There was a
      significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC
      cohort compared with the historical control cohort. No differences were
      identified in the use of other blood products as well as other secondary efficacy
      or safety end points. CONCLUSIONS: Use of PCC, per the reversal protocol, prior
      to heart transplant reduced FFP use and showed a non-statistically significant
      trend toward reductions in the use of other blood products in the intraoperative
      and perioperative setting, with no difference identified in thrombotic or embolic
      complications compared with historical controls.

PMID- 25986008
TI  - Performance of a divided-load intravenous vancomycin dosing strategy for obese
      patients.
AB  - BACKGROUND: Current guidelines recommend vancomycin trough concentrations of 15
      to 20 ug/mL in complicated infections and all trough concentrations >10 ug/mL to
      avoid developing microbial resistance. To date, no published protocol reliably
      meets these recommendations for obese patients. OBJECTIVE: We assessed the
      performance of a novel, obese-specific, divided-load vancomycin protocol for
      attaining target trough concentrations within 12 to 24 hours of dosing
      initiation, and during maintenance dosing, in obese patients. METHODS: The
      protocol was evaluated through prospective medical record review in 54
      consecutive obese patients. Vancomycin serum concentrations were drawn before the
      third and fifth dose after initiation. Steady-state concentrations were drawn
      after the third dose once maintenance dosing was achieved and periodically
      thereafter. RESULTS: Within 12 hours after dosing initiation, 48 (89%) study
      patients exhibited trough concentrations of 10 to 20 ug/mL averaging 14.5 +/- 3.2
      ug/mL; 51 (94%) study patients exhibited trough concentrations >10 ug/mL within
      12 hours after dosing initiation, and 3 (6%) had trough concentrations >20 ug/mL.
      Thirty-one participants had second trough concentrations drawn within 24 hours of
      dosing initiation, averaging 15.0 +/- 3.1 ug/mL; 24 patients had a total of 32
      trough concentrations drawn during maintenance dosing, averaging 15.1 +/- 2.5
      ug/mL. CONCLUSION: Obese-specific, divided-load dosing achieved trough
      concentrations of 10 to 20 ug/mL for 89% of obese patients within 12 hours of
      initial dosing and 97% of obese patients within 24 hours of initial dosing while
      preventing doses given during supratherapeutic trough levels; 97% of troughs
      measured during steady state were within target range.

PMID- 25986009
TI  - Liraglutide: an injectable option for the management of obesity.
AB  - OBJECTIVE: To review the efficacy and safety of liraglutide, marketed as Saxenda,
      a glucagon-like peptide-1 analog for obesity management. DATA SOURCES: A MEDLINE
      search (1970 to March 2015) was conducted for English-language articles using the
      terms glucagon-like peptide 1, liraglutide, and obesity. STUDY SELECTION AND DATA
      EXTRACTION: Published articles pertinent to the efficacy and safety of
      liraglutide for short- and long-term obesity management among overweight or obese
      patients and special populations were reviewed and summarized. DATA SYNTHESIS:
      Based on randomized placebo-controlled and active-comparator studies, liraglutide
      can increase weight loss among overweight and obese patients in a dose-dependent
      manner with once-daily doses of 1.2 to 3.0 mg. It has been shown that a higher
      proportion of patients experienced 5% and 10% weight loss from baseline compared
      with placebo and orlistat. Data support the potential benefit of liraglutide
      among overweight and obese patients with prediabetes, as well as women with
      polycystic ovary syndrome (PCOS) with an inadequate response to metformin. Larger
      and more robust studies are needed to determine the clinical significance of
      liraglutide among other agents for obesity in diverse populations. CONCLUSIONS:
      Liraglutide is an adjunct to lifestyle modifications to improve success rates
      among overweight or obese individuals without diabetes. It may have a potential
      role in special populations, such as in those with prediabetes and women with
      PCOS. Based on its clinical evidence, liraglutide can result in more weight loss
      from baseline compared with orlistat and placebo. Adverse events associated with
      liraglutide are primarily gastrointestinal and usually dose dependent.

PMID- 25986010
TI  - Association study of genetic variants at newly identified lipid gene TRIB1 with
      coronary heart disease in Chinese Han population.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have identified the
      variants near TRIB1 gene affecting blood lipid levels. However, the association
      between the reported variants and risk of coronary heart disease (CHD) was not
      confirmed. METHODS: We conducted two independent case-control studies. The first
      study consisted of 300 CHD patients and 300 controls and the second study had
      1,332 CHD patients and 2,811 controls. The genotypes of two variants rs3201475
      and rs17321515 in TRIB1 were determined by TaqMan assay. The dual-luciferase
      reporter assay was performed for evaluating the function of the SNP rs3201475.
      RESULTS: The statistical analysis indicated that single nucleotide polymorphism
      (SNP) rs17321515 was replicated to be associated with triglyceride (TG) level,
      which was also significantly associated with CHD risk when using the stratified
      analysis after adjusting for conventional risk factors. Compared with GG
      genotype, AA carriers of SNP rs17321515 had higher risk in males (odds ratio
      (OR)=1.28, 95%CI=1.01-1.61; P=0.03) and smokers (OR=1.41, 95%CI=1.09-1.88;
      P=0.01). We did not find significantly association between genotypes of rs3201475
      and CHD risk. In addition, no significant difference was found in the luciferase
      activity assay of SNP rs3201475. CONCLUSIONS: Our findings indicated that SNP
      rs17321515 is significantly associated with plasma TG level and the increasing
      risk of CHD among males and smokers in Chinese, whereas there is no positive
      association between SNP rs3201475 and CHD risk. Smoking could modify the effects
      of TRIB1 on CHD risk.

PMID- 25986011
TI  - MSC and innate immune cell interactions: A lesson from human decidua.
AB  - Both experimental and clinical studies revealed that stromal cells (SC) are
      present in decidua (DSC) and placenta (PSC) at the early and late phase of
      pregnancy, respectively, and they may contribute to the induction of an anti
      inflammatory/tolerogenic microenvironment crucial for the
      establishment/maintenance of successful pregnancy. These cells share common
      features with mesenchymal SC. In the present contribution, we provide an overall
      view on DSC features and on their ability to recruit NK cells and to regulate
      both differentiation and function not only of NK cells but also of CD14(+)
      myeloid cells. NK cells represent the large majority of leukocytes populating
      decidual tissues during the first trimester of pregnancy. Their cross-talk with
      DSC is thought to play a key role in the establishment of feto-maternal
      tolerance. We also discuss recent data suggesting that DSC may contribute to
      tissue remodeling, placentation, and recruitment of leukocytes also through their
      interaction with innate lymphoid cells (ILC) such as ILC3, that have recently
      been shown to be present in decidual tissue. 

PMID- 25986012
TI  - Commonalities in immune modulation between mesenchymal stem cells (MSCs) and
      neural stem/precursor cells (NPCs).
AB  - Owing to their unique immunomodulatory properties, mesenchymal stem cells (MSCs)
      have been advocated as a potential therapy for numerous pathological conditions
      in which immune-mediated inflammatory reactions play a crucial role, such as
      autoimmune disorders, cerebrovascular diseases and tumours. Increasing evidence
      suggest that stem cells, other than MSCs, are also capable of immunomodulation.
      Neural stem/precursor cells (NPCs) have been among the first stem cells to show
      immunomodulatory properties and nowadays represent one the most studied and
      promising stem cell subtype in still uncurable acute and chronic inflammatory
      neurological disorders. Although the ontogeny of NPCs and MSCs greatly diverges,
      their immunomodulatory mechanisms are similar and are largely based on the
      bystander (paracrine) effect through membrane-bound and soluble mediators that
      influence the behavior of host immune cells. This observation suggests the
      existence of a core stem cell signature across different stem cell lineages and
      that shared signalling pathways between the stem cell niche and the inflammatory
      immune response likely mediate both NPC and MSC immunomodulatory effect. 

PMID- 25986013
TI  - Functionally and morphologically distinct populations of extracellular vesicles
      produced by human neutrophilic granulocytes.
AB  - EVs in the microvesicle size range released during spontaneous death of human
      neutrophils were characterized and their properties compared with previously
      described EVs with antibacterial effect (aEVs, generated on specific activation)
      or produced spontaneously (sEVs). The 3 vesicle populations overlapped in size
      and in part of the constituent proteins were stained with annexin V and were
      impermeable to PI. However, none of them produced superoxide. In contrast,
      remarkable differences were observed in the morphology, abundance of proteins,
      and antibacterial function. EVs formed spontaneously in 30 min (sEVs) were more
      similar to EVs released during spontaneous death in 1-3 d than to EVs formed in
      30 min on stimulation of opsonin receptors (aEVs). Spontaneously generated EVs
      had no antibacterial effect despite their large number and protein content. We
      hypothesized 2 parallel mechanisms: one that proceeds spontaneously and produces
      EVs without antibacterial effect and another process that is triggered by opsonin
      receptors and results in differential sorting of proteins into EVs with
      antibacterial capacity. Our results call attention to the functional and
      morphologic heterogeneity within the microvesicle/ectosome fraction of EVs. 

PMID- 25986015
TI  - A trigger tool to detect harm in pediatric inpatient settings.
AB  - OBJECTIVES: An efficient and reliable process for measuring harm due to medical
      care is needed to advance pediatric patient safety. Several pediatric studies
      have assessed the use of trigger tools in varying inpatient environments. Using
      the Institute for Healthcare Improvement's adult-focused Global Trigger Tool as a
      model, we developed and pilot tested a trigger tool that would identify the most
      common causes of harm in pediatric inpatient environments. METHODS: After formal
      training, 6 academic children's hospitals used this novel pediatric trigger tool
      to review 100 randomly selected inpatient records per site from patients
      discharged during the month of February 2012. RESULTS: From the 600 patient
      charts evaluated, 240 harmful events ("harms") were identified, resulting in a
      rate of 40 harms per 100 patients admitted and 54.9 harms per 1000 patient days
      across the 6 hospitals. At least 1 harm was identified in 146 patients (24.3% of
      patients). Of the 240 total events, 108 (45.0%) were assessed to have been
      potentially or definitely preventable. The most common patient harms were
      intravenous catheter infiltrations/burns, respiratory distress, constipation,
      pain, and surgical complications. CONCLUSIONS: Consistent with earlier rates of
      all-cause harm in adult hospitals, harm occurs at high rates in hospitalized
      children. Availability and use of an all-cause harm identification tool will
      establish the epidemiology of harm and will provide a consistent approach to
      assessing the effect of interventions on harms in hospitalized children.

PMID- 25986014
TI  - NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular
      helper cells during a chronic virus infection.
AB  - There is a need to understand better how to improve B cell responses and immunity
      to persisting virus infections, which often cause debilitating illness or death.
      People with chronic virus infection show evidence of improved virus control when
      there is a strong neutralizing antibody response, and conversely, B cell
      dysfunction is associated with higher viral loads. We showed previously that NK
      cells inhibit CD4(+) and CD8(+) T cell responses to disseminating LCMV infection
      and that depletion of NK cells attenuates chronic infection. Here, we examined
      the effect of NK cell depletion on B cell responses to LCMV infection in mice.
      Whereas mice infected acutely generated a peak level of antibody soon after the
      infection was resolved, mice infected chronically showed a continued increase in
      antibody levels that exceeded those after acute infection. We found that early NK
      cell depletion rapidly increased virus-specific antibody levels to chronic
      infection, and this effect depended on CD4(+) T cells and was associated with
      elevated numbers of CXCR5(+)CD4(+) TFH cells. However, the NK cell-depleted mice
      controlled the infection and by 1 mo pi, had lower TFH cell numbers and antibody
      levels compared with mice with sustained infection. Finally, we show that NK cell
      depletion improved antiviral CD8(+) T cell responses only when B cells and virus
      specific antibody were present. Our data indicate that NK cells diminish immunity
      to chronic infection, in part, by suppressing TFH cell and antibody responses. 

PMID- 25986016
TI  - Active play opportunities at child care.
AB  - BACKGROUND AND OBJECTIVES: Physical activity (PA) is important for children's
      health and development, yet preschoolers are not meeting PA recommendations. The
      objective of this study was to examine different PA opportunities at child care
      and how variation in indoor versus outdoor and free versus teacher-led
      opportunities relate to children's PA. METHODS: An observational study of 98
      children (mean age 4.5 years, 49% girls) from 10 child care centers. Classrooms
      were observed for at least 4 full days per center (total 50 days) to categorize
      time into (1) not an active play opportunity (APO); (2) naptime; (3) APO, outdoor
      free play; (4) APO, outdoor teacher-led; (5) APO, indoor free play; and (6) APO,
      indoor teacher-led. Children wore accelerometers during observations. Linear
      regression models examined the influence of APO categories on moderate-vigorous
      physical activity (MVPA) and sedentary time. RESULTS: Children's activity was 73%
      sedentary, 13% light, and 14% MVPA. For 88% of time children did not have APOs,
      including 26% time as naptime. On average, 48 minutes per day were APOs (41%
      sedentary, 18% light, and 41% MVPA), 33 minutes per day were outdoors. The most
      frequent APO was outdoor free play (8% of time); outdoor teacher-led time was
      <1%. Children were more active and less sedentary outdoors versus indoors and
      during the child-initiated APOs (indoors and outdoors) versus teacher-led APOs.
      CONCLUSIONS: Preschoolers were presented with significantly fewer than
      recommended opportunities for PA at child care. More APOs are needed for children
      to meet recommendations, particularly those that encourage more outdoor time,
      more teacher-led and child-initiated active play, and flexibility in naptime for
      preschoolers.

PMID- 25986017
TI  - Sedentary time in late childhood and cardiometabolic risk in adolescence.
AB  - BACKGROUND AND OBJECTIVE: There is a paucity of prospective evidence examining
      the links between sedentary time (ST) and cardiometabolic outcomes in youth. We
      examined the associations between objectively assessed ST and moderate to
      vigorous physical activity (MVPA) in childhood with cardiometabolic risk in
      adolescence. METHODS: The study included 4639 children (47% male) aged 11 to 12
      years at baseline whose mothers were enrolled in ALSPAC (Avon Longitudinal Study
      of Parents and Children) during their pregnancy in the early 1990s. A total of
      2963 children had valid blood samples at age 15 to 16 years. Associations with
      baseline ST and MVPA were examined for BMI, waist circumference, body fat mass,
      lean body mass, systolic and diastolic blood pressure, fasting triglycerides,
      total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL)
      cholesterol, glucose, insulin, C-reactive protein, and a clustered standardized
      cardiometabolic risk score (CMscore). RESULTS: Baseline ST was not associated
      deleteriously with any cardiometabolic markers. MVPA was beneficially associated
      with the 3 adiposity indicators, lean body mass, systolic blood pressure,
      triglycerides, C-reactive protein, insulin, HDL cholesterol, and CMscore; once
      the models were adjusted for baseline levels of these markers, these associations
      remained for body fat mass (mean difference per 10 minutes of MVPA: -0.320 [95%
      confidence interval (CI): -0.438 to -0.203]; P < .001), HDL cholesterol (0.006
      logged mmol/L [95% CI: 0.001 to 0.011]; P = .028), insulin (-0.024 logged IU/L
      [95% CI: -0.036 to -0.013]; P < .001), and CMscore (-0.014 [95% CI: -0.025 to 
      0.004]; P = .009). CONCLUSIONS: We found no evidence linking ST in late childhood
      with adverse cardiometabolic outcomes in adolescence. Baseline MVPA was
      beneficially linked to broad cardiometabolic health in adolescence.

PMID- 25986019
TI  - Head growth and neurocognitive outcomes.
AB  - BACKGROUND AND OBJECTIVES: There is a lack of evidence on the value of head
      circumference (HC) as a screening measure. We aimed to describe the incidence of
      head centile shifting and the relationship between extremes of head size and
      later neurodevelopmental problems in the Avon Longitudinal Study of Parents and
      Children. METHODS: HC was measured routinely at 2, 9, and 18 or 24 months and by
      researchers at ages 4, 8, 12, and 18 months. IQ according to the Wechsler
      Intelligence Scale for Children was measured in research clinics at age 8 for
      all. Neurocognitive disorders (NCDs) were identified from chart review. RESULTS:
      There were 10 851 children with >=2 head measurements. At each age, 2% to 3% of
      children had scores that were < -2 or >2 SDs below or above the mean, but for
      most children this was only found at 1 age. More than 15% of children showed
      centile shifts, but less than one-third of these were sustained at subsequent
      measurements. Only 0.5% showed a sustained shift beyond the normal range.
      Children with consistently small heads were up to 7 times more likely to have an
      NCD, but 85% of children with small heads had no NCDs, and 93% of children with
      NCDs had head SD scores within the normal range. CONCLUSIONS: Centile shifts
      within the normal range occur commonly and seem mainly to reflect measurement
      error. This finding makes robust assessment of the head trajectory difficult and
      may result in many children being investigated unnecessarily. Extreme head size
      is neither specific nor sensitive for detecting NCDs, suggesting that routine
      measurement of HC is unhelpful.

PMID- 25986018
TI  - Long-chain polyunsaturated fatty acids and cognition in VLBW infants at 8 years:
      an RCT.
AB  - OBJECTIVE: To test the hypothesis that supplementation with the long chain
      polyunsaturated fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA)
      to very low birth weight (VLBW) infants would improve long-term cognitive
      functions and influence neuroanatomical volumes and cerebral cortex measured by
      MRI. METHODS: The current study is a follow-up of a randomized, double-blinded,
      placebo-controlled study of supplementation with high-dose DHA (0.86%) and AA
      (0.91%) to 129 VLBW infants fed human milk. Ninety-eight children participated at
      8 years follow-up and completed a broad battery of cognitive tests. Eighty-one
      children had cerebral MRI scans of acceptable quality. RESULTS: There were no
      significant differences between the intervention group and the control group on
      any of the cognitive measures. Equally, MRI data on segmental brain volumes and
      cerebral cortex volume, area, and thickness suggested no overall group effect.
      CONCLUSIONS: This study is the first long-term follow-up of a randomized
      controlled trial with supplementation of DHA and AA to human milk fed VLBW
      infants investigating both cognitive functions and brain macrostructure measured
      by MRI. No cognitive or neuroanatomical effects of the supplementation were
      detected at 8 years of age.

PMID- 25986020
TI  - Is zero central line-associated bloodstream infection rate sustainable? A 5-year
      perspective.
AB  - BACKGROUND AND OBJECTIVE: Adoption and implementation of evidence-based measures
      for catheter care leads to reductions in central line-associated bloodstream
      infection (CLABSI) rates in the NICU. The purpose of this study is to evaluate
      whether this rate reduction is sustainable for at least 1 year and to identify
      key determinants of this sustainability at the NICU of the Floating Hospital for
      Children at Tufts Medical Center. METHODS: We reviewed the incidence of CLABSIs
      in the NICU temporally to the implementation of new practice policies and
      procedures, from July 2008 to December 2013. RESULTS: Adoption of standardized
      care practices, including bundles and checklists, was associated with a
      significant reduction of the CLABSI rate to zero for >370 consecutive days in our
      NICU in 2012. Overall, our CLABSI rates decreased from 4.1 per 1000 line days in
      2009 (13 infections; 3163 line days) to 0.94 in 2013 (2 infections; 2115 line
      days), which represents a 77% reduction over a 5-year period. In the first
      quarter of 2013, there was a brief increase in CLABSI rate to 3.3 per 1000 line
      days; after a series of interventions, the CLABSI rate was maintained at zero for
      >600 days. Ongoing training, surveillance, and vigilance with catheter insertion
      and maintenance practices and improved documentation were identified as key
      drivers for success. CONCLUSIONS: High-quality training, strict compliance with
      evidence-based guidelines, and thorough documentation is associated with
      significant reductions in CLABSIs. Mindful organizing may lead to a better
      understanding of what goes into a unit's ability to handle peak demands and
      sustain extraordinary performance in the long-term.

PMID- 25986021
TI  - Bronchiolitis obliterans organizing pneumonia due to gastroesophageal reflux.
AB  - The most common causes of bronchiolitis obliterans organizing pneumonia (BOOP)
      are connective tissue diseases, organ transplantation, drug reaction, and
      infections. Although rare, BOOP due to gastroesophageal reflux (GER) has been
      reported in adults but not to date in pediatric patients. This study describes 2
      pediatric patients who developed GER and BOOP. One patient had superior
      mesenteric artery syndrome and Helicobacter pylori infection, and the other had a
      gastroduodenal ulcer with reflux esophagitis. Respiratory symptoms occurred
      concurrently or after gastrointestinal symptoms. Monitoring of esophageal pH for
      24 hours revealed pathologic acid reflux. Lung biopsy findings confirmed BOOP. No
      other causes of BOOP were observed in these 2 patients. Both patients were cured
      with antireflux therapy and corticosteroids. To our knowledge, this is the first
      case report to implicate GER as a reversible cause of BOOP in children. 

PMID- 25986022
TI  - Vincristine for successful treatment of steroid-dependent infantile hemangiomas.
AB  - Infantile hemangiomas (IHs) are common, although systemic therapy has been
      generally limited to circumstances of potential compromise of vital functions
      (airway, vision, feeding, or cardiac), risk of disfigurement, or bleeding. IHs
      have previously been shown to express high levels of type III deiodinase, which
      catabolizes active thyroid hormone, resulting in a state of severe
      hypothyroidism, termed "consumptive hypothyroidism." We describe an infant with
      diffuse hepatic hemangiomas who developed consumptive hypothyroidism who was
      initially treated successfully with systemic glucocorticoids and beta-blockers.
      Several efforts to wean her medications were unsuccessful. She subsequently
      developed severe growth restriction and treatment alternatives were sought.
      Although previously limited to treatment of life-threatening hemangiomas, a trial
      of vincristine was initiated. She was ultimately weaned from all systemic
      therapies, with recovery of a normal growth trajectory. This case highlights
      broader indications for vincristine as a safe and effective systemic therapy for
      treatment of IHs. It also stresses the importance of close anthropometric
      monitoring of infants and toddlers receiving glucocorticoid therapy and
      intervention when growth compromise becomes evident. 

PMID- 25986023
TI  - Physical activity in youth dance classes.
AB  - BACKGROUND AND OBJECTIVES: The majority of youth are not meeting the US
      Department of Health and Human Services physical activity guidelines. Dance is a
      popular activity, particularly for girls, and has the potential to increase
      physical activity for many youth. This study investigated physical activity of
      children and adolescents in 7 dance types: ballet, hip-hop, jazz, Latin-flamenco,
      Latin-salsa/ballet folklorico, partnered, and tap. METHODS: Data were collected
      in 17 private studios and 4 community centers in San Diego, California. A total
      of 264 girls from 66 classes participated (n =154 children; n = 110 adolescents).
      Physical activity was measured with accelerometers, and activity levels during
      class were calculated. RESULTS: Participants recorded an average of 17.2 +/- 8.9
      minutes of moderate-to-vigorous physical activity (36% of class), but this varied
      by age and dance type. For children, dance type differences were observed with
      percent of class in moderate-to-vigorous physical activity ranging from 13.6%
      (Latin-flamenco) to 57% (hip-hop). For adolescents, there were no differences
      across dance types. Children were more active than adolescents in all types
      except ballet. Children and adolescents were more active in private compared with
      community center classes. CONCLUSIONS: Overall, physical activity in youth dance
      classes was low; 8% of children and 6% of adolescents met the Centers for Disease
      Control and Prevention 30-minute guideline for after-school physical activity
      during dance. To increase physical activity in dance classes, teaching methods
      could be employed to increase activity in all types, or emphasis could be placed
      on greater participation in more active dance types.

PMID- 25986024
TI  - Transition: changing old habits.

PMID- 25986025
TI  - Validity of bronchiolitis outcome measures.
AB  - BACKGROUND: The Respiratory Distress Assessment Instrument (RDAI) and Respiratory
      Assessment Change Score (RACS) are frequently used in bronchiolitis clinical
      trials, but evidence is limited on their measurement properties. We investigated
      their validity, reliability, and responsiveness. METHODS: We included data from
      up to 1765 infants with bronchiolitis enrolled in 2 studies conducted in
      pediatric emergency departments. We assessed RDAI construct validity by testing
      hypotheses of associations with physiologic measures (respiratory rate, oxygen
      saturation) and with constructs related to hospitalization, using correlation
      coefficients, and multivariable analysis. RDAI/RACS responsiveness was evaluated
      by using anchors of change based on these constructs; measures of responsiveness
      included the area under the curve. RDAI test-retest agreement and interrater
      reliability were evaluated by using limits of agreement and intraclass
      correlation coefficients. RESULTS: Baseline RDAI scores were weakly correlated
      with respiratory rate (r = 0.38, P < .001), and scores increased in lower oxygen
      saturation categories (P < .001). Higher RDAI scores were associated with
      hospitalization (odds ratio: 1.36; 95% confidence interval: 1.26-1.47); scores
      differed between participants who were discharged, admitted, or stayed in the
      emergency department (P < .001). Our hypotheses were met, but the magnitude of
      associations was below our predefined thresholds. RDAI test-retest limits of
      agreement were -3.80 to 3.64 (20% of the range), whereas interrater reliability
      was good (intraclass correlation coefficient = 0.93). Formulated hypotheses for
      responsiveness were confirmed, with moderate responsiveness (area under the
      curve: RDAI, 0.64-0.70; RACS, 0.72). CONCLUSIONS: RDAI has poor to moderate
      construct validity, with good discriminative properties but considerable test
      retest measurement error. The RDAI and RACS are responsive measures of
      respiratory distress in bronchiolitis but do not encompass all determinants of
      disease severity.

PMID- 25986027
TI  - Glycerin enemas and suppositories in premature infants: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Premature infants are often given glycerin enemas or
      suppositories to facilitate meconium evacuation and transition to enteral
      feeding. The purpose of this study was to assess the available evidence for this
      treatment strategy. METHODS: We conducted a systematic search of Medline, Embase,
      Central, and trial registries for randomized controlled trials of premature
      infants treated with glycerin enemas or suppositories. Data were extracted in
      duplicate and meta-analyzed using a random effects model. RESULTS: We identified
      185 premature infants treated prophylactically with glycerin enemas in one trial
      (n = 81) and suppositories in two other trials (n = 104). All infants were less
      than 32 weeks gestation and had no congenital malformations. Treatment was
      associated with earlier initiation of stooling in one trial (2 vs 4 days, P =
      .02) and a trend towards earlier meconium evacuation in another (6.5 vs 9 days, P
      = .11). Meta-analysis demonstrated no effect on transition to enteral feeding
      (0.7 days faster, P = .43) or mortality (P = 0.50). There were no reports of
      rectal bleeding or perforation but there was a trend towards increased risk of
      necrotizing enterocolitis with glycerin enemas or suppositories (risk ratio =
      2.72, P = .13). These three trials are underpowered and affected by one or more
      major methodological issues. As a result, the quality of evidence is low to very
      low. Three other trials are underway. CONCLUSIONS: The evidence for the use
      glycerin enemas or suppositories in premature infants in inconclusive. Meta
      analyzed data suggest that treatment may be associated with increased risk of
      necrotizing enterocolitis. Careful monitoring of ongoing trials is required.

PMID- 25986026
TI  - The long and short of it: long-chain fatty acids and long-term outcomes for
      premature infants.

PMID- 25986028
TI  - CYP2C19*17 genetic polymorphism--an uncommon cause of voriconazole treatment
      failure.
AB  - We describe an immunosuppressed, 48-year-old male, allogeneic hematopoietic stem
      cell transplant recipient with severe graft-versus-host disease who developed
      invasive pulmonary Aspergillus fumigatus infection 6 months after transplant. His
      lack of response to voriconazole and undetectable serum trough levels of the drug
      led us to establish that he had the uncommon cytochrome P450, CYP2C19*17 allele,
      which leads to a rapid metabolism of voriconazole but not of the other azole
      antifungals. We discuss the particular challenges encountered in this case.

PMID- 25986029
TI  - Isavuconazole, micafungin, and 8 comparator antifungal agents' susceptibility
      profiles for common and uncommon opportunistic fungi collected in 2013: temporal
      analysis of antifungal drug resistance using CLSI species-specific clinical
      breakpoints and proposed epidemiological cutoff values.
AB  - The in vitro activities of isavuconazole, micafungin, and 8 comparator antifungal
      agents were determined for 1613 clinical isolates of fungi (1320 isolates of
      Candida spp., 155 of Aspergillus spp., 103 of non-Candida yeasts, and 35 non
      Aspergillus molds) collected during a global survey conducted in 2013. The vast
      majority of the isolates of the 21 different species of Candida, with the
      exception of Candida glabrata (MIC90, 2 MUg/mL), Candida krusei (MIC90, 1
      MUg/mL), and Candida guilliermondii (MIC90, 8 MUg/mL), were inhibited by <=0.25
      MUg/mL of isavuconazole. C. glabrata and C. krusei were largely inhibited by <=1
      MUg/mL of isavuconazole. Resistance to fluconazole was seen in 0.5% of Candida
      albicans isolates, 11.1% of C. glabrata isolates, 2.5% of Candida parapsilosis
      isolates, 4.5% of Candida tropicalis isolates, and 20.0% of C. guilliermondii
      isolates. Resistance to the echinocandins was restricted to C. glabrata (1.3
      2.1%) and C. tropicalis (0.9-1.8%). All agents except for the echinocandins were
      active against 69 Cryptococcus neoformans isolates, and the triazoles, including
      isavuconazole, were active against the other yeasts. Both the mold active
      triazoles as well as the echinocandins were active against 155 Aspergillus spp.
      isolates belonging to 10 species/species complex. In general, there was low
      resistance levels to the available systemically active antifungal agents in a
      large, contemporary (2013), global collection of molecularly characterized yeasts
      and molds. Resistance to azoles and echinocandins was most prominent among
      isolates of C. glabrata, C. tropicalis, and C. guilliermondii.

PMID- 25986030
TI  - Perioperative morbidity and rate of upstaging after laparoscopic staging for
      patients with locally advanced cervical cancer: results of a prospective
      randomized trial.
AB  - OBJECTIVE: The International Federation of Gynecology and Obstetrics (FIGO)
      staging for cervical cancer is based on clinical examination. Previous studies
      have demonstrated significant upstaging with surgical staging. However, no
      randomized trial has ever shown a survival benefit when radiation combined with
      chemoradiation (RCTX) is modified according to surgical staging. The objective of
      the study was to evaluate the feasibility and outcomes of surgical staging prior
      to radical RCTX treatment among patients with locally advanced cervical cancer in
      the setting of a larger, prospective, randomized study (the Uterus-11 study of
      the German Gynecologic Oncology Group). STUDY DESIGN: Between 2009 and 2013, 255
      patients with advanced cervical cancer (FIGO IIB-IVA) were randomized to surgical
      staging and RCTX (arm A) or RCTX (arm B). RCTX in both arms included pelvic
      external beam radiotherapy with weekly cisplatin at 40 mg/m(2) and brachytherapy.
      Extended-field radiation was performed in cases of confirmed paraaortic
      metastases. RESULTS: One hundred thirty patients were randomized to surgical
      staging; 121 were eligible for this analysis. The mean patient age was 47.2
      years, and the mean body mass index was 26.2 kg/m(2); the FIGO stages were IIB,
      IIIA, IIIB, and IVA in 85 (70.2%), 4 (3.3%), 29 (24%), and 3 (2.5%) patients,
      respectively. Arm A and arm B were similar with respect to Karnofsky performance
      status, histology, comorbidities, and lymphovascular space involvement. The
      surgical approach was transperitoneal laparoscopy in nearly all patients (93.4%),
      with no operative mortality. One patient (0.8%) had a conversion to laparotomy; 2
      patients had more than 500 mL blood loss; the early postoperative complication
      rate was 7.3%. A mean of 19 pelvic and 17 paraaortic nodes were removed, with
      means of 2.4 and 1.3 positive nodes, respectively. RCTX began between 7 and 21
      days after surgery. Operative staging led to upstaging in 40 of 121 (33%).
      CONCLUSION: Surgical staging in patients with locally advanced cervical cancer is
      safe and does not delay primary RCTX in a randomized study.

PMID- 25986031
TI  - Metastatic adenocarcinoma to the clitoris from the cervix.

PMID- 25986032
TI  - Marijuana use in pregnancy and lactation: a review of the evidence.
AB  - With the legalization of recreational marijuana in many states, we anticipate
      more women will be using and self-reporting marijuana use in pregnancy. Marijuana
      is the most common illicit drug used in pregnancy, with a prevalence of use
      ranging from 3% to 30% in various populations. Marijuana freely crosses the
      placenta and is found in breast milk. It may have adverse effects on both
      perinatal outcomes and fetal neurodevelopment. Specifically, marijuana may be
      associated with fetal growth restriction, stillbirth, and preterm birth. However,
      data are far from uniform regarding adverse perinatal outcomes. Existing studies
      are plagued by confounding by tobacco and other drug exposures as well as
      sociodemographic factors. In addition, there is a lack of quantification of
      marijuana exposure by the trimester of use and a lack of corroboration of
      maternal self-report with biological sampling, which contributes to the
      heterogeneity of study results. There is an emerging body of evidence indicating
      that marijuana may cause problems with neurological development, resulting in
      hyperactivity, poor cognitive function, and changes in dopaminergic receptors. In
      addition, contemporary marijuana products have higher quantities of delta-9
      tetrahydrocannabinol than in the 1980s when much of the marijuana research was
      completed. The effects on the pregnancy and fetus may therefore be different than
      those previously seen. Further research is needed to provide evidence-based
      counseling of women regarding the anticipated outcomes of marijuana use in
      pregnancy. In the meantime, women should be advised not to use marijuana in
      pregnancy or while lactating. 

PMID- 25986033
TI  - Noninvasive prenatal testing for 22q11.2 deletion syndrome: deeper sequencing
      increases the positive predictive value.

PMID- 25986034
TI  - The impact of chorionicity on maternal pregnancy outcomes.
AB  - OBJECTIVE: Women carrying twin pregnancies often receive similar counseling,
      regardless of chorionicity, with the notable exception of twin-twin transfusion
      syndrome (TTTS); however, little is known about whether the presence of 1 vs 2
      placentas confers dissimilar maternal risks. We sought to determine differences
      in maternal and neonatal outcomes based on chorionicity. STUDY DESIGN: This was a
      retrospective cohort study of all twin pregnancies at our institution undergoing
      routine second-trimester ultrasound for anatomic survey from 1990 through 2010.
      Secondary outcomes included other adverse maternal and neonatal outcomes.
      Relative risks and adjusted odds ratios (aORs) were calculated. Cluster analysis
      was used to account for nonindependence of twin pairs. RESULTS: Of 2301
      pregnancies, 1747 (75.9%) were dichorionic and 554 (24.1%) were monochorionic.
      Rates of preeclampsia, gestational diabetes, placental abruption, placenta
      previa, preterm labor, and preterm premature rupture of membranes (PPROM) were
      not significantly different in dichorionic vs monochorionic pregnancies. Early
      preterm delivery less than 34 weeks (aOR, 1.47; 95% confidence interval [CI],
      1.17-1.86) and less than 28 weeks (aOR, 2.58; 95% CI, 1.58-4.20) were more likely
      in monochorionic twins, as was neonatal intensive care unit admission (aOR, 1.41;
      95% CI, 1.12-1.78). Monochorionic twins delivered earlier at a mean gestational
      age of 34.2 weeks vs 35.0 weeks for dichorionic twins (P < .001). Hospital length
      of stay was significantly longer for monochorionic twins with a mean of 13.7 days
      vs 10.8 days for dichorionic twins (P = .01). CONCLUSION: There are no
      significant differences in maternal outcomes by chorionicity; however,
      monochorionicity is associated with increased fetal risks. This information may
      be helpful in guiding more targeted counseling to expectant parents of twins
      that, although the presence of an additional placenta does not confer additional
      maternal risks, monochorionic infants tend to deliver earlier and require longer
      hospital stays.

PMID- 25986035
TI  - Accumulation of energy reserves in algae: From cell cycles to biotechnological
      applications.
AB  - Starch and lipids are key components of algal cells and responsible for buffering
      variable supplies of energy and carbon that are vital for cell growth and
      reproduction, particularly DNA replication, nuclear and cellular division. The
      basic characteristics of energy reserves, their ultrastructure and localization
      inside the cell, regulation of their synthesis in relation to cell cycle phases,
      and their control by external factors, including light intensity, temperature,
      and carbon dioxide are described. Over the last two decades, research in this
      field has been boosted by possible biotechnological applications of algae for the
      production of biofuels from energy conserving compounds (bioethanol from starch
      and biodiesel from lipids). Recent findings on mechanisms that lead to an
      accumulation of exceptionally high levels of starch and lipids in algae will be
      summarized in this review. Macroelement (N, S, P) limitation, or depletion in
      mineral medium, as the most widely used approaches for enhancing both starch and
      lipid accumulation, are reviewed in detail. Potential biotechnological strategies
      for the economically viable overproduction of lipid and starch, such as a two
      step procedure exploiting the effects of nutrient limitation and depletion, as
      well as the means and rationale for selecting appropriate strains, are discussed.

PMID- 25986036
TI  - Prevalence of cardiovascular and metabolic events in patients prescribed
      clozapine: a retrospective observational, clinical cohort study.
AB  - BACKGROUND: The efficacy of clozapine for the treatment of schizophrenia has been
      demonstrated. However, a range of adverse events have been associated with its
      use. To date, there remains a paucity of data regarding the prevalence of
      clozapine-induced cardiovascular (CV) and parameters associated with the
      development of metabolic syndrome, alongside associated risk factors for their
      development. METHODS: An observational, clinical cohort study design of 355
      clozapine patients who were enrolled in the Barwon Health Clozapine Program at
      Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were
      accessed retrospectively. Multivariate logistic regression was used to determine
      associations with adverse event(s). RESULTS: Older age of commencement with
      clozapine was consistently associated with increased risk of CV abnormalities,
      with the exception of tachycardia where older age was protective (Odds Ratio
      [OR]: 0.97; 95% Confidence Intervals [CI]: 0.95, 0.99). Males had significantly
      greater odds of most metabolic disturbances with the exception of being obese
      (BMI: >=30 OR: 0.45; 95% CIs: 0.24, 0.85). Older age of commencement was a
      significantly associated variable with High- Density Lipoprotein-cholesterol (OR:
      1.03; 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04; 95% CIs: 1.02, 1.07). An
      increase in BMI was consistently and significantly associated with all metabolic
      events. CONCLUSION: Male patients who are obese at any point during treatment and
      older at treatment commencement may be the most vulnerable to adverse CV and
      metabolic events. While future studies using a matched case-control design may be
      required to verify these findings, we recommend that treating clinicians consider
      these risks when assessing patient suitability to clozapine therapy.

PMID- 25986037
TI  - Clinical implications of patient-provider agreements in opioid prescribing.
AB  - In June, 2012 the United States Food and Drug Administration (FDA) developed a
      "blueprint" for prescriber education as a means of directing Certified Medical
      Education (CME) activities that included content which would meet the regulatory
      requirements of the class-wide, longacting/ extended-release (LA-ER) opioid Risk
      Evaluation Mitigation Strategies (REMS). Within the blueprint is the suggested
      adoption of Patient-Provider Agreements (PPAs) to be used in association with
      opioid prescribing, but, to our knowledge, there have been no reported
      evaluations of the role played by opioid-agent PPAs in clinical practice, or of
      the perceptions of this regulatory mandate by clinicians. Therefore, we conducted
      a survey regarding PPA perceptions by opioid prescribers that was posted for five
      weeks on a well-trafficked online CME service provider (Medscape). Of the 1,232
      respondents (reflecting a 99.5% completion rate), 52.4% treat acute or chronic
      pain with opioids. The survey identified an improvement of opioid safe-use
      education (21% of respondents) as the most frequently selected beneficial element
      of PPAs. Conversely, the challenges to adoption included time constraints (21% of
      physicians) as well as lack of evidence that PPAs will reduce drug misuse, and
      the lack of a uniform, patient-friendly PPA. Based on our survey, clinicians
      consider the PPA of potential value, but data regarding the utility of such an
      instrument are lacking.

PMID- 25986038
TI  - The use of metronidazole during pregnancy: a review of evidence.
AB  - OBJECTIVE: To review the available evidence concerning the relationship between
      the exposure to metronidazole during pregnancy and the risk of preterm delivery
      and birth defects. METHODS: Studies investigating the association between
      gestational use of oral metronidazole on human subjects and the risk of preterm
      birth or/and birth defects were systematically retrieved from MEDLINE and EMBASE
      databases. We selected studies published in English or French between 1964 and
      2012. Where effect estimates were not reported, crude ORs along with 95%
      confidence intervals were calculated. RESULTS: We selected 17 studies
      investigating the association between exposure to oral metronidazole and the risk
      of preterm birth, from which 12 were randomized clinical trials. In addition, we
      identified 13 studies devoted to the relationship between metronidazole and birth
      defects, from which 10 were cohort studies, 1 was a case-control study and 2 were
      meta-analysis. CONCLUSION: During pregnancy, treating bacterial vaginosis and
      trichomoniasis with metronidazole is effective and offers no teratogen risk.
      Benefit of metronidazole in the reduction of preterm birth was demonstrated for
      the combination of this medication with other antibiotics. Additional information
      is needed when metronidazole is used in association with other agents.

PMID- 25986039
TI  - Acute kidney injury, hyperbilirubinemia, and ischemic skin necrosis due to
      massive sulindac overdose.
AB  - Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used
      for the management of osteoarthritis, rheumatoid arthritis, ankylosing
      sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the
      literature are rare. We report the case of a 22-year old male with a history of
      bipolar disorder who was brought to the emergency department after ingesting
      approximately 15 g of sulindac in a suicide attempt. He was found to have acute
      kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his
      renal function progressively worsened requiring the initiation of hemodialysis.
      Ten days following ingestion of sulindac, he began to develop ischemic skin
      changes with a gangrenous appearance in his hands and feet. He continued to
      receive supportive treatment, and his acute kidney injury, hyperbillirubinemia,
      and ischemic skin necrosis eventually resolved. Clinicians should be aware of
      this long-acting NSAID and its ability to cause prolonged multisystem organ
      dysfunction. 

PMID- 25986040
TI  - Drug development from natural resource: a systematic approach.
AB  - Modern research in drug discovery from medicinal plants involves a
      multidimensional approach combining botanical, phytochemical, biochemical
      combinatorial chemistry and bioassay-guided fractionation approaches. Natural
      sources continue to provide an alternative as pharmacological leads against
      various devastating diseases such as diabetes, CVD, cancer etc. Nowadays, there
      is enormous requirement of safe and effective drugs in the world. This has
      prompted scientists to revert back towards natural resources as a potential
      source of therapeutics for treatment and management of such chronic and fatal
      diseases. However, there are certain serious challenges and limitations in this
      field including scale up and commercialization of active compounds which allow
      only one in thousand lead molecules to be developed as drug. A systematic and
      scientific approach is an essential requirement for drug development from natural
      resource. This mini review provides an overview of the methods involved in
      natural product research starting from crude plant extract to bioactive
      pharmacological lead. Moreover, it also discusses the limitations of working
      concerning the bioactivity of medicinal plants. 

PMID- 25986041
TI  - Change in organizational justice and job performance in Japanese employees: A
      prospective cohort study.
AB  - OBJECTIVE: The aim of the present study was to investigate the association of one
      year change in organizational justice (i.e., procedural justice and interactional
      justice) with job performance in Japanese employees. METHODS: This study surveyed
      425 men and 683 women from a manufacturing company in Japan. Self-administered
      questionnaires, including the Organizational Justice Questionnaire (OJQ), the
      World Health Organization Health and Work Performance Questionnaire (WHO-HPQ) and
      the scales on demographic characteristics, were administered at baseline (August
      2009). At one-year follow-up (August 2010), the OJQ and WHO-HPQ were used again
      to assess organizational justice and job performance. The change in
      organizational justice was measured by dichotomizing each OJQ subscale score by
      median at baseline and follow-up, and the participants were classified into four
      groups (i.e., stable low, adverse change, favorable change and stable high).
      Analysis of covariance (ANCOVA) was employed. RESULTS: After adjusting for
      demographic and occupational characteristics and job performance at baseline, the
      groups classified based on the change in procedural justice differed
      significantly in job performance at follow-up (ANCOVA: F [3, 1097]=4.35, p<0.01).
      Multiple comparisons revealed that the stable high procedural justice group had
      significantly higher job performance at follow-up compared with the stable low
      procedural justice group. The groups classified based on change in interactional
      justice did not differ significantly in job performance at follow-up (p>0.05).
      CONCLUSIONS: The present findings suggest that keeping the level of procedural
      justice high predicts higher levels of job performance, whereas the psychosocial
      factor of interactional justice is not so important for predicting job
      performance.

PMID- 25986042
TI  - Evaluation of urinary cyclohexanediols and cyclohexanol as biomarkers of
      occupational exposure to cyclohexane.
AB  - OBJECTIVES: The aim of the present study was to comparatively evaluate the
      usefulness of urinary cyclohexanediols (CHdiols-U) and cyclohexanol (CHol-U) as
      biomarkers of occupational exposure to cyclohexane (CH). METHODS: Sixteen
      subjects (14 men and 2 women) were exposed to CH during proof-printing work.
      Personal exposure monitoring was conducted during the whole shift on the last
      working day of the week. The time-weighted average level of exposure to CH (CH-A)
      was measured using a diffusive sampler. Two urine samples were collected from
      each worker at different times during the same week: a baseline urine sample
      (before the first shift of the working week, after a 5-day holiday with no CH
      exposure) and an end-of-shift urine sample (after the last shift of the same
      working week, the same day personal exposure monitoring was conducted). CH-A,
      CHdiols-U and CHol-U were determined using a gas chromatograph-flame ionization
      detector. RESULTS: The CH-A concentrations ranged from 4.5 to 60.3 ppm, with a
      geometric mean (GM) of 18.1 ppm. The GMs and ranges (in parenthesis) of the
      creatinine (cr)-corrected end-of-shift 1,2-CHdiol-U, 1,4-CHdiol-U and CHol-U
      concentrations were 12.1 (4.1-36.6), 7.5 (2.4-20.1) and 0.4 (0.2-1.0) mg/g cr,
      respectively. Both CHdiols-U at the end of the shift were significantly
      correlated with CH-A (correlation coefficients for 1,2-CHdiol-U and 1,4-CHdiol-U
      of 0.852 and 0.847, respectively). No correlation was observed between CH-A and
      CHol-U. CONCLUSIONS: CHdiols-U at the end of the last shift of the working week
      are suitable biomarkers of occupational exposure to CH, but CHol-U is not
      suitable.

PMID- 25986043
TI  - Estimation of biological occupational exposure limit values for selected organic
      solvents from logartihm of octarol water partition coefficient.
AB  - OBJECTIVES: For several organic solvents (solvents in short), biological
      occupational exposure limits (BOELs) have been established for un-metabolized
      solvents in urine, based on the solvent exposure-urinary excretion relationship.
      This study was initiated to investigate the possibiliy of estimating a BOEL from
      the Pow (the partition coefficient between n-octyl alcohol and water), a physico
      chemical parameter. METHODS: Data were available in the literatures for exposure
      excretion relationship with regard to 10 solvents for men and 7 solvents for
      women. RESULTS: Statistical analysis revealed that the slopes (after correction
      for molecular weights and logarithmic conversion) of the exposure-excretion
      regression lines linearly correlated (p<0.01) with the log Pow values the
      respective solvents. No significant difference (p>0.05) was observed between men
      and women, and it was acceptable to combine the data for the two sexes. Thus the
      log Pow-log slope relation was represented by a single equation for both sexes.
      Based on the observations, procedures were established to estimate BOEL values
      from Pow. Successful estimations of BOELs for styrene, tetrahydrofuran and m
      xylene (a representative of xylene isomers) were calculated as examples.
      CONCLUSIONS: The present study proposed promising procedures for estimation of a
      BOEL from the Pow.

PMID- 25986044
TI  - The management of malignant polyps in colorectal cancer screening programmes: A
      retrospective Italian multi-centre study.
AB  - BACKGROUND: Although recognition of colorectal malignant polyps is increasing,
      treatment plans lack the evidence of randomised trials. AIM: To retrospectively
      evaluate presentation, management and outcomes of screen-detected colorectal
      malignant polyps, with special focus on the role of histological factors in
      therapeutic decision-making. METHODS: We retrospectively analysed data regarding
      malignant polyps detected during faecal immuno-chemical test-based screening
      programmes in five centres in North-Eastern Italy between April 2008 and April
      2013. RESULTS: 306 malignant polyps in 306 patients were included; 72 patients
      underwent surgery directly (23.6%). Of 234 patients treated endoscopically, 133
      subsequently underwent radicalisation surgery (56.8%) and in 17 there was
      evidence of residual disease (12.8%). Involved, unsafe (<1mm) or invaluable
      resection margins and sessile morphology represented the most frequent
      determinants of subsequent surgery. The mean number of nodes harvested during
      radicalisation surgery was 7.1+/-6.4 (range 0-29). Histological diagnosis was re
      evaluated according to new guidelines in 125 cases (41%); in 18 this led to
      modification of the risk class (14.4%). CONCLUSIONS: Although the rate of
      surgical treatment following endoscopic resection is similar to other studies,
      residual disease at surgery was lower than most international series. Adhering to
      the new histological reporting system and respecting guidelines on node
      harvesting may favourably influence prognosis.

PMID- 25986045
TI  - Prostate Cancer Education, Detection, and Follow-Up in a Community-Based
      Multiethnic Cohort of Medically Underserved Men.
AB  - The Prostate Outreach Project (POP) provided free prostate cancer (PCa) education
      and early detection to medically underserved communities. POP recruited
      participants in medically underserved communities. PCa education and detection
      events occurred in POP locations (static) or natural gathering places (mobile)
      within the community. PCa education was delivered by video and evaluated using a
      questionnaire. Screening consisted of serum prostate-specific antigen and digital
      rectal examination. A navigated follow-up strategy was utilized to provide
      medical care for participants with abnormal screening examinations (ASE). POP
      recruited 4,420 men, 62.8% (2,667) were African American (AA). Most participants
      had a high school education and no prior screening. Fifty-four percent (2,159)
      were uninsured and 41% (1,811) had no access to a physician. PCa knowledge
      increased following the educational video. Prostate-specific antigen levels were
      elevated in 9.8% (436), while 6.9% (233) had an abnormal digital rectal
      examination. Follow-up among 609 men with ASE was successful in 40% (244),
      despite a navigated approach. Overall, 3.3% (144) cancers were diagnosed among
      the POP with AA participants exhibiting a significantly higher incidence.
      Recruitment, education, and PCa testing among a medically underserved cohort was
      successful. However, failure to follow through on ASE could contribute to
      maintaining the disparity in PCa outcomes noted among AAs and the medically
      underserved if not addressed.

PMID- 25986047
TI  - Molecular markers of anti-malarial drug resistance in southwest Ethiopia over
      time: regional surveillance from 2006 to 2013.
AB  - BACKGROUND: Drug resistance is one of the main reasons of anti-malarial treatment
      failures and impedes malaria containment strategies. As single nucleotide
      polymorphisms (SNPs) have been found to correlate with anti-malarial drug
      resistance, the surveillance strategy includes continuous monitoring of known
      molecular markers and detection of new mutation patterns. With the introduction
      of artemisinin-based combination therapy, selection of specific patterns has been
      observed worldwide. METHODS: From March to June 2013, whole blood was collected
      on filter paper from microscopically malaria positive patients in Jimma zone
      (District), southwestern Ethiopia. Plasmodium falciparum, Plasmodium vivax and
      mixed infections were included. SNPs were investigated by conventional or real
      time PCR, restriction fragment length pattern analysis or sequencing. Results
      were compared to molecular patterns from Ethiopian isolates in 2004, 2006 and
      2008/9. RESULTS: Plasmodium falciparum, P. vivax, and mixed infections were
      molecularly confirmed in 177, 80, and 14 samples, respectively. In P. falciparum,
      mutations in the pfcrt, pfmdr 1and pfATP 6 (SERCA) gene were investigated.
      Whereas the mutation in the pfcrt gene at codon 76 K was still found in 95.6% of
      all samples, the pfmdr 1 86 T mutation fell to 1.2% (2/163) in 2013 compared to
      9% in 2008/9 and 86% in 2006 (P<0.001). The pfmdr 1 184 F mutation dominated with
      100.0% (172/172) in 2013. Sequencing of the recently reported PF3D7_1343700 kelch
      propeller domain showed no mutation at codon 476. First sequencing data of the
      pvmdr 1 gene from Jimma region revealed a prevalence of the mutations 976 F and
      1076 L in 72.7% (16/23) and 100.0% (19/19) of the isolates, respectively.
      CONCLUSION: Since the introduction of artemether-lumefantrine (AL) in Jimma,
      Ethiopia, in 2006, the prevalence of certain SNPs associated with AL use has
      increased. Markers for chloroquine resistance in P. vivax were highly frequent.
      Continuous molecular and clinical surveillance are of paramount importance.

PMID- 25986048
TI  - Development of construction materials using nano-silica and aggregates recycled
      from construction and demolition waste.
AB  - The present work addresses the development of novel construction materials
      utilising commercial grade nano-silica and recycled aggregates retrieved from
      construction and demolition waste. For this, experimental work has been carried
      out to examine the influence of nano-silica and recycled aggregates on
      compressive strength, modulus of elasticity, water absorption, density and volume
      of voids of concrete. Fully natural and recycled aggregate concrete mixes are
      designed by replacing cement with three levels (0.75%, 1.5% and 3%) of nano
      silica. The results of the present investigation depict that improvement in early
      days compressive strength is achieved with the incorporation of nano-silica in
      addition to the restoration of reduction in compressive strength of recycled
      aggregate concrete mixes caused owing to the replacement of natural aggregates by
      recycled aggregates. Moreover, the increase in water absorption and volume of
      voids with a reduction of bulk density was detected with the incorporation of
      recycled aggregates in place of natural aggregates. However, enhancement in
      density and reduction in water absorption and volume of voids of recycled
      aggregate concrete resulted from the addition of nano-silica. In addition, the
      results of the study reveal that nano-silica has no significant effect on elastic
      modulus of concrete.

PMID- 25986046
TI  - A seven-gene CpG-island methylation panel predicts breast cancer progression.
AB  - BACKGROUND: DNA methylation regulates gene expression, through the
      inhibition/activation of gene transcription of methylated/unmethylated genes.
      Hence, DNA methylation profiling can capture pivotal features of gene expression
      in cancer tissues from patients at the time of diagnosis. In this work, we
      analyzed a breast cancer case series, to identify DNA methylation determinants of
      metastatic versus non-metastatic tumors. METHODS: CpG-island methylation was
      evaluated on a 56-gene cancer-specific biomarker microarray in metastatic versus
      non-metastatic breast cancers in a multi-institutional case series of 123 breast
      cancer patients. Global statistical modeling and unsupervised hierarchical
      clustering were applied to identify a multi-gene binary classifier with high
      sensitivity and specificity. Network analysis was utilized to quantify the
      connectivity of the identified genes. RESULTS: Seven genes (BRCA1, DAPK1, MSH2,
      CDKN2A, PGR, PRKCDBP, RANKL) were found informative for prognosis of metastatic
      diffusion and were used to calculate classifier accuracy versus the entire data
      set. Individual-gene performances showed sensitivities of 63-79 %, 53-84 %
      specificities, positive predictive values of 59-83 % and negative predictive
      values of 63-80 %. When modelled together, these seven genes reached a
      sensitivity of 93 %, 100 % specificity, a positive predictive value of 100 % and
      a negative predictive value of 93 %, with high statistical power. Unsupervised
      hierarchical clustering independently confirmed these findings, in close
      agreement with the accuracy measurements. Network analyses indicated tight
      interrelationship between the identified genes, suggesting this to be a
      functionally-coordinated module, linked to breast cancer progression.
      CONCLUSIONS: Our findings identify CpG-island methylation profiles with deep
      impact on clinical outcome, paving the way for use as novel prognostic assays in
      clinical settings.

PMID- 25986051
TI  - Regulation of Protein Binding Capability of Surfaces via Host-Guest Interactions:
      Effects of Localized and Average Ligand Density.
AB  - The protein binding capability of biomaterial surfaces can significantly affect
      subsequent biological responses, and appropriate ligand presentation is often
      required to guarantee the best functions. Herein, a new facile method for
      regulating this capability by varying the localized and average ligand density is
      presented. Binding between lysine and plasminogen relevant to a fibrinolysis
      system was chosen as a model. We integrated different lysine-modified beta
      cyclodextrin (beta-CD) derivatives onto bioinert copolymer brushes via host-guest
      interactions. The localized and average lysine density can be conveniently
      modulated by changing the lysine valency on beta-CD scaffolds and by diluting
      lysine-persubstituted beta-CD with pure beta-CD, respectively. Both the
      plasminogen adsorption and the plasminogen binding affinity were enhanced by
      lysine-persubstituted beta-CD compared with those of lysine-monosubstituted beta
      CD, which is possibly due to the higher localized lysine density and the
      multivalent binding of plasminogen on lysine-persubstituted beta-CD surfaces.
      With a change in the ratio of lysine-persubstituted beta-CD to beta-CD, the
      average lysine density can be tuned, leading to the linear regulation of the
      adsorption of plasminogen on surfaces. 

PMID- 25986052
TI  - Nanostructured porous manganese carbonate spheres with capacitive effects on the
      high lithium storage capability.
AB  - In this paper, nanostructured porous MnCO3 spheres are facilely synthesized,
      which can simultaneously provide an increased surface for conversion reaction and
      capacitive storage as the anode material for lithium ion batteries. This material
      gives a superior specific capacity and excellent long-term cycling performance
      even at a high current density. It can deliver a stable capacity of 1049 mA h g(
      1) after 200 cycles at a current density of 1000 mA g(-1), which is much higher
      than the theoretical capacity of 466 mA h g(-1). After 2000 cycles at a high
      current density of 5000 mA g(-1), a capacity of 510 mA h g(-1) can still be
      maintained. Their high rating performance at 5000 mA g(-1) is among the best
      reported performances of anode materials. From the in situ or ex situ SEM
      observation, the porous MnCO3 nanostructure can provide a stable template for
      reversible lithium insertion and extraction without significant morphology change
      and accommodate the volume change during the charge-discharge process. Also this
      structure increases the capacitive contribution to the total capacity compared
      with other MnCO3 samples. 

PMID- 25986050
TI  - Molecular characterization of an MYB transcription factor from a succulent
      halophyte involved in stress tolerance.
AB  - Abiotic stresses like drought, salinity and extreme temperature significantly
      affect crop productivity. Plants respond at molecular, cellular and physiological
      levels for management of stress tolerance. Functional and regulatory genes play a
      major role in controlling these abiotic stresses through an intricate network of
      transcriptional machinery. Transcription factors are potential tools for
      manipulating stress tolerance since they control a large number of downstream
      genes. In the present study, we have isolated SbMYB44 from a succulent halophyte,
      Salicornia brachiata Roxb. SbMYB44 with an open-reading frame of 810 bp encodes a
      protein of 269 amino acids, with an estimated molecular mass of 30.31 kDa and an
      isoelectric point of 6.29. The in silico analysis revealed that the SbMYB44
      protein contains the conserved R2R3 imperfect repeats, two SANT domains and post
      translational modification sites. The SbMYB44 transcript showed up-regulation in
      response to salinity, desiccation, high temperature, and abscisic acid and
      salicylic acid treatments. The SbMYB44 recombinant protein showed binding to
      dehydration-responsive cis-elements (RD22 and MBS-1), suggesting its possible
      role in stress signalling. Overexpression of SbMYB44 enhanced the growth of yeast
      cells under both ionic and osmotic stresses. 

PMID- 25986053
TI  - Position- and polarity-dependent Hippo signaling regulates cell fates in
      preimplantation mouse embryos.
AB  - During the preimplantation stage, mouse embryos establish two cell lineages by
      the time of early blastocyst formation: the trophectoderm (TE) and the inner cell
      mass (ICM). Historical models have proposed that the establishment of these two
      lineages depends on the cell position within the embryo (e.g., the positional
      model) or cell polarization along the apicobasal axis (e.g., the polarity model).
      Recent findings have revealed that the Hippo signaling pathway plays a central
      role in the cell fate-specification process: active and inactive Hippo signaling
      in the inner and outer cells promote ICM and TE fates, respectively.
      Intercellular adhesion activates, while apicobasal polarization suppresses Hippo
      signaling, and a combination of these processes determines the spatially
      regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore,
      there is experimental evidence in favor of both positional and polarity models.
      At the molecular level, phosphorylation of the Hippo-pathway component angiomotin
      at adherens junctions (AJs) in the inner (apolar) cells activates the Lats
      protein kinase and triggers Hippo signaling. In the outer cells, however, cell
      polarization sequesters Amot from basolateral AJs and suppresses activation of
      the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch
      signaling, also play important roles in the regulation of embryonic development.
      In this review, I discuss how these mechanisms cooperate with the Hippo signaling
      pathway during cell fate-specification processes. 

PMID- 25986054
TI  - Human mononuclear phagocyte system reunited.
AB  - The human mononuclear phagocyte network comprises dendritic cells (DCs),
      monocytes and macrophages with a range of immune functions including antigen
      presentation linking innate and adaptive immunity. A number of DC, monocyte and
      macrophage subsets have been described in lymphoid and non-lymphoid tissues of
      mouse and human, with increased understanding of their distinct functional
      properties and genetic and cellular pathways of development. More recently,
      through comparative biology studies, a unified nomenclature of mononuclear
      phagocytes has begun to emerge with the identification of homologous subsets in
      several species. In this review, we discuss the current classification of human
      mononuclear phagocytes and the parallel organization of this network in the
      mouse. We also review the genetic control and developmental pathway of human
      mononuclear phagocytes and the immunological functions of the distinct subsets in
      health and inflammation. 

PMID- 25986056
TI  - How Ebola has been evolving in West Africa.
AB  - The ongoing Ebola outbreak in West Africa has generated fears of a global
      epidemic. Particularly, estimates of higher substitution rates have raised
      concerns about increased transmissibility or virulence. A recent study using a
      more comprehensive datasets demonstrates lower variation, highlighting the
      importance of representative datasets and limitations of computational modelling.

PMID- 25986055
TI  - Spatial and temporal aspects of Wnt signaling and planar cell polarity during
      vertebrate embryonic development.
AB  - Wnt signaling pathways act at multiple locations and developmental stages to
      specify cell fate and polarity in vertebrate embryos. A long-standing question is
      how the same molecular machinery can be reused to produce different outcomes. The
      canonical Wnt/beta-catenin branch modulates target gene transcription to specify
      cell fates along the dorsoventral and anteroposterior embryonic axes. By
      contrast, the Wnt/planar cell polarity (PCP) branch is responsible for cell
      polarization along main body axes, which coordinates morphogenetic cell behaviors
      during gastrulation and neurulation. Whereas both cell fate and cell polarity are
      modulated by spatially- and temporally-restricted Wnt activity, the downstream
      signaling mechanisms are very diverse. This review highlights recent progress in
      the understanding of Wnt-dependent molecular events leading to the establishment
      of PCP and linking it to early morphogenetic processes. 

PMID- 25986057
TI  - Parental feeding practices and child weight status in Mexican American families:
      a longitudinal analysis.
AB  - BACKGROUND: Parental feeding practices are thought to influence children's weight
      status, through children's eating behavior and nutritional intake. However,
      because most studies have been cross-sectional, the direction of influence is
      unclear. Moreover, although obesity rates are high among Latino children, few
      studies of parental feeding practices have focused on this population. METHODS:
      This 2-year longitudinal study examined mutual influences over time between
      parental feeding practices and children's weight status, in Mexican American
      families with children 18 years old at baseline. Mothers (n = 322) and fathers (n
      = 182) reported on their feeding practices at baseline, 1-year follow-up, and 2
      year follow-up. Weight status, defined by waist-height ratio (WHtR) and body mass
      index (BMI), was ascertained at all assessments. Cross-lagged panel models were
      used to examine the mutual influences of parental feeding practices and child
      weight status over time, controlling for covariates. RESULTS: Both mothers' and
      fathers' restriction of food predicted higher subsequent child weight status at
      Year 1, and for fathers this effect was also found at Year 2. Mothers' and
      fathers' pressure to eat predicted lower weight status among boys, but not girls,
      at Year 1. Child weight status also predicted some parental feeding practices:
      boys' heavier weight predicted mothers' less pressure to eat at Year 1, less use
      of food to control behavior at Year 2, and greater restriction at Year 2; and
      girls' heavier weight at Year 1 predicted fathers' less pressure to eat and less
      positive involvement in child eating at Year 2. CONCLUSIONS: This study provides
      longitudinal evidence that some parental feeding practices influence Mexican
      American children's weight status, and that children's weight status also
      influences some parental feeding practices. Feeding practices of both mothers and
      fathers were related to children's weight status, underscoring the importance of
      including fathers in research on parental feeding practices and child obesity.

PMID- 25986058
TI  - Delayed Gastric Emptying (DGE) Following Total Pancreatectomy with Islet Auto
      Transplantation in Patients with Chronic Pancreatitis.
AB  - BACKGROUND: The prevalence and factors associated with delayed gastric emptying
      (DGE) in patients undergoing total pancreatectomy with islet auto transplantation
      (TP-IAT) for chronic pancreatitis are unknown. METHODS: A retrospective study of
      all patients who underwent TP-IAT at Johns Hopkins Hospital (JHH) from August
      2011 to November 2014 was performed. The International Study Group of Pancreatic
      Surgery (ISGPS) clinical grading of DGE was used in this study. KEY RESULTS: A
      total of 39 patients with chronic pancreatitis underwent TP-IAT during the study
      period. The prevalence of DGE following TP-IAT was 35.9%. Twenty-five patients
      (64.1%) had no DGE, 10 (25.6%) had grade A, 2 (5.1%) had grade B, and 2 patients
      (5.1%) had grade C DGE. Patients with DGE had 5.7-fold higher odds of having a
      hospital length of stay (LOS) greater than 14 days (OR 5.70, 95% CI 1.37-23.76, p
      = 0.02). Patients undergoing laparoscopic TP-IAT had significantly shorter LOS
      (10.5 vs. 14 days, p = 0.02) and lower need for prokinetics (0.01) during the
      postoperative course. CONCLUSIONS AND INFERENCES: DGE is common after TP-IAT and
      can prolong LOS. Laparoscopic TP-IAT lowers LOS and need for prokinetics
      postoperatively. Further studies are needed to determine if laparoscopic
      approaches will improve long-term dysmotility.

PMID- 25986059
TI  - Single incision laparoscopic resection for diverticulitis.
AB  - BACKGROUND: Laparoscopic sigmoidectomy is the standard procedure in elective
      surgery for recurrent diverticular disease. Recently, Single Incision
      Laparoscopic Surgery (SILS) have been developed as the next generation technique
      of minimally invasive surgery. SILS advantages include reduced surgical trauma
      due to reduction in the number of surgical incisions, faster recovery times, and
      reduced hospitalization. However, the use of SILS in colorectal surgery is
      technically demanding and requires expert surgeons, which has hampered the
      reproducibility and the diffusion of this technique. METHODS: Between October
      2009 and August 2013, 488 consecutive patients were referred to Evangelisches
      Hochstift Hospital (Worms, Germany) and/or Stadt Klinikum Frankental Hospital
      (Frankenthal, Germany) for sigmoidectomy for diverticular disease. SILS
      sigmoidectomy via the umbilicus was performed in 484/488 cases. Clinical outcomes
      such as the rate of conversion to standard laparoscopy and/or to open surgery,
      operation time, post-operative complications and hospitalization time were
      recorded. RESULTS: SILS sigmoidectomy was successfully completed for 484 out of
      488 patients. SILS was converted to standard laparoscopy in 3 patients (0.6%) and
      to an open procedure in 1 patient (0.2%). Median time for the procedures was
      103.26 min (range, 52-156 min). No mortalities or major complications were noted.
      The average hospitalization period was of 5 days. CONCLUSION: Our work
      demonstrates that SILS sigmoidectomy via the umbilicus is effective in the
      treatment of patients affected by diverticular disease on a routine basis and,
      moreover, is technically feasible also in patients who have been subjected to
      previous abdominal surgery, with high Body Mass Index and/or patients with
      perforation at presentation. Thus this procedure represents a valid alternative
      to standard laparoscopy.

PMID- 25986060
TI  - Laparoscopic assisted versus open gastric pull-up following thoracoscopic
      esophagectomy: A cohort study.
AB  - BACKGROUND: Thoracolaparoscopic esophagectomy (TLE) is a type of minimally
      invasive esophagectomy (MIE) for esophageal cancer which consists of
      thoracoscopic resection and laparoscopic reconstruction. The aim of the present
      study was to evaluate the technical and oncological feasibility of alimentary
      tract reconstruction with laparoscopically assisted gastric pull-up (LAG)
      following thoracoscopic esophagectomy in the prone position (TSEP) in comparison
      with reconstruction with open laparotomy gastric pull-up (OLG) following TSEP, to
      establish TLE with extended lymph node dissection as a standard operation for
      esophageal cancer. METHODS: Sixty-four patients with esophageal cancer underwent
      TSEP with 3-field lymphadenectomy from 2008 through 2010: for reconstruction
      after TSEP, 31 patients underwent LAG, and 33 patients underwent OLG. We
      retrospectively evaluated the technical and oncological feasibility of TLE with 3
      field lymphadenectomy and compared surgical outcomes after reconstruction with
      OLG and that with LAG. RESULTS: TLE with 3-field lymphadenectomy was successfully
      completed in 30 of 31 (97%) patients, and no surgery-related postoperative deaths
      occurred. No significant difference was found between LAG and OLG in the mean
      number of dissected abdominal lymph nodes, amount of blood loss, incidence of
      postoperative complications, mean postoperative hospital stay, restoration rate
      of respiratory function, or rate of complete resection or locoregional control,
      but the mean duration of abdominal procedures was significantly longer with LAG
      than with OLG. CONCLUSION: This study demonstrates that the quality and safety of
      surgery and the oncological effectiveness of LAG for esophageal cancer. TLE
      consisting of LAG following TSEP with extended lymph-node dissection is a
      feasible surgical technique for thoracic esophageal carcinoma.

PMID- 25986061
TI  - Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical
      challenge.
AB  - Adenosquamous carcinoma of the breast (ASBC) is a rare variant of metaplastic
      breast cancer with both glandular as well as squamous differentiation. Their lack
      of distinct imaging characteristics, sometimes subtle histological
      characteristics and overlapping features with other benign lesions pose a
      diagnostic challenge. Unlike other forms of metaplastic breast cancer, low-grade
      adenosquamous carcinoma (LGAC) tends to follow an indolent course with favourable
      prognosis. We reviewed eight cases of LGAC in our institution from June 2005 to
      March 2014. In six cases, LGAC was only found after excisional biopsy. In our
      patients, LGAC frequently co-existed with other forms of breast pathology. Two
      patients had incidental findings of LGAC alongside their primary malignant tumour
      (adenoid cystic carcinoma and invasive ductal carcinoma in one, four foci between
      0.5 and 4.0 mm within a radial sclerosing lesion adjacent to a malignant
      phyllodes tumour in the other). A further four patients had LGAC within a complex
      sclerosing lesion. One patient had a focus of LGAC within a fibroadenoma. One had
      a focus of LGAC within a benign phyllodes tumour. None of the patients had
      evidence of nodal involvement. A high degree of suspicion is recommended as such
      lesions tend to be incidental histological findings within benign tumours or
      within complex sclerosing lesions. Although the risk of nodal and distant
      metastasis is low, the potential for local recurrence necessitates aggressive
      local excision with margin clearance. The role of axillary dissection has yet to
      be defined and routine sentinel node biopsy and axillary clearance may not be
      necessary in view of rarity of nodal metastasis in literature. Benefit from
      adjuvant radiotherapy or chemotherapy is not clearly defined. All eight patients
      in our study have shown no evidence of recurrence after definitive surgery but
      longer periods of surveillance is required. 

PMID- 25986062
TI  - The Stability of Extreme Response Style and Acquiescence Over 8 Years.
AB  - This study investigated the stability of extreme response style (ERS) and
      acquiescence response style (ARS) over a period of 8 years. ERS and ARS were
      measured with item sets drawn randomly from a large pool of items used in an
      ongoing German panel study. Latent-trait-state-occasion and latent-state models
      were applied to test the relationship between time-specific (state) response
      style behaviors and time-invariant trait components of response styles. The
      results show that across different random item samples, on average between 49%
      and 59% of the variance in the state response style factors was explained by the
      trait response style factors. This indicates that the systematic differences
      respondents show in their preferences for certain response categories are
      remarkably stable over a period of 8 years. The stability of ERS and ARS implies
      that it is important to consider response styles in the analysis of self-report
      data from polytomous rating scales, especially in longitudinal studies aimed at
      investigating stability in substantive traits. Furthermore, the stability of
      response styles raises the question in how far they might be considered trait
      like latent variables themselves that could be of substantive interest.

PMID- 25986063
TI  - Global Call to Action: maximize the public health impact of intermittent
      preventive treatment of malaria in pregnancy in sub-Saharan Africa.
AB  - Intermittent preventive treatment of malaria in pregnancy is a highly cost
      effective intervention which significantly improves maternal and birth outcomes
      among mothers and their newborns who live in areas of moderate to high malaria
      transmission. However, coverage in sub-Saharan Africa remains unacceptably low,
      calling for urgent action to increase uptake dramatically and maximize its public
      health impact. The 'Global Call to Action' outlines priority actions that will
      pave the way to success in achieving national and international coverage targets.
      Immediate action is needed from national health institutions in malaria-endemic
      countries, the donor community, the research community, members of the
      pharmaceutical industry and private sector, along with technical partners at the
      global and local levels, to protect pregnant women and their babies from the
      preventable, adverse effects of malaria in pregnancy. 

PMID- 25986065
TI  - Effects of dietary selenium on apoptosis of germ cells in the testis during
      spermatogenesis in roosters.
AB  - The aim of this study was to determine the effects of dietary selenium (Se)
      supplementation on apoptosis of germ cells in the testis during spermatogenesis
      in roosters. Eighty 12-week-old Hy-Line Variety white roosters with an averaged
      body weight of 1.38 +/- 0.2 kg were selected and randomly divided into four
      experimental groups. They were fed the basal diet (0.044 mg/kg Se dry matter)
      supplemented with 0 (control), 0.5, 1.0, or 2.0 mg/kg of Se dry matter (from
      sodium selenite). After the 45-day feeding experiment, testis samples were
      collected from the roosters of each treatment group to detect the population of
      apoptotic germ cells using the terminal deoxynucleotidy1 transferase dUTP nick
      end labeling assay. The protein expression of cell cycle-related genes and the
      messenger RNA (mRNA) expression of apoptosis and cell cycle-related genes had
      also been detected. The results show that the population of apoptotic germ cells
      in the control and 2.0 mg/kg groups was increased (P < 0.05) compared with that
      in the 0.5 mg/kg and 1.0 mg/kg groups. Expressions of CDC2 and CCNB1 protein in
      the control and 2.0 mg/kg groups were lower (P < 0.05) than those in the 0.5
      mg/kg and 1.0 mg/kg groups. The mRNA level of CDC2 in the 0.5 mg/kg group was
      higher (P < 0.05) than that in other groups. The lowest (P < 0.05) mRNA
      expressions of apoptosis-related genes (BCL-2, CASPASE 3, CASPASE 8) were also
      obtained in the 0.5 mg/kg group. These results show that dietary Se of roosters
      can affect apoptosis of germ cells by regulating the mRNA expressions of
      apoptosis- and cell cycle-related genes in the testis during spermatogenesis. 

PMID- 25986066
TI  - Reproductive performance of Brown Swiss, Holstein and their crosses under
      subtropical environmental conditions.
AB  - Selection has been emphasized for increasing production traits with ignoring the
      fertility traits, which leads to a general loss of reproductive fitness. The aim
      of this study was to evaluate the reproductive performance of the pure Brown
      Swiss (BS), Holstein (HO), their first-generation crossbred (F1), and backcross
      (BC) cows under subtropical Egyptian conditions. The reproductive performance and
      health traits were measured in the pure BS, HO, their F1, and BC crossbred, in
      addition to investigating the impact of temperature-humidity index level (THI) on
      reproductive traits. Brown Swiss and her F1 had a better reproductive efficiency
      and health traits than in HO and BC. They possess a higher conception (34.1% and
      36.9%, respectively) and pregnancy rates (32.8% and 31.1%, respectively), a
      shorter calving interval (401 and 420 days, respectively), and a lower average
      insemination per parturition (3.18 and 3.45, respectively), with a lower
      incidence of metritis (14.1% and 14.6%, respectively). Moreover, no difference
      has been detected in the fertility of BS with different THI levels, whereas F1
      was slightly affected by increasing THI, especially for conception rate which
      declined from 43.1% at low to 24.1% at high THI. But the pregnancy rate did not
      change with different levels of THI. Our results indicate that BS and her F1 have
      a better reproductive performance and adaptability than pure HO and BC under
      subtropical Egyptian conditions. Furthermore, milk yield of the F1 crossbred is
      comparable to that of the pure HO cows. 

PMID- 25986064
TI  - Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEXTM is an
      independent prognostic marker for breast cancer patients.
AB  - BACKGROUND: Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly
      expressed epithelial cell surface antigen and has evolved to be the most
      predictive serum tumour marker in breast cancer. PankoMab-GEXTM, which is
      currently being evaluated for its therapeutic efficacy in a phase IIb clinical
      trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour
      associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the
      immunoreactivity of PankoMabGEXTM and its correlation with established clinico
      pathological variables including 10-year and overall survival in a large cohort
      of breast cancer patients. METHODS: Breast cancer tissue sections (n = 227)
      underwent a standardized immunohistochemical staining protocol for TA-MUC1 by
      using PankoMab-GEXTM as a primary antibody. The staining was evaluated by two
      independent observers and quantified by applying the IR-score. RESULTS: TA-MUC1
      as detected by PankoMab-GEXTM was identified in 74.9% of breast cancer tissue
      sections. Patients were subdivided according to the subcellular localisation of
      TA-MUC1 and cases classified as mem-PankoMab-GEXTM (solely membranous) positive,
      cyt-PankoMab-GEXTM (solely cytoplasmic) positive, double positive or as
      completely negative were compared regarding their survival. Herein mem-PankoMab
      GEXTM-positive patients performed best, while double-negative ones presented with
      a significantly shortened survival. Positivity for mem-PankoMab-GEXTM as well as
      a double-negative immunophenotype turned out to be independent prognosticators
      for survival. CONCLUSIONS: This is the first study to report on PankoMab-GEXTM in
      a large panel of breast cancer patients. The PankoMab-GEXTM epitope TA-MUC1 could
      be identified in the majority of cases and was found to be an independent
      prognosticator depending on its subcellular localisation. Since TA-MUC1 is known
      to be highly immunogenic cancers staining positive for PankoMab-GEXTM might be
      more compromised by host anti-tumour immune defence. Further, the observations
      reported here might be fundamental for selecting patients to undergo PankoMab
      GEXTM-containing chemotherapy protocols.

PMID- 25986067
TI  - Testosterone-receptor positive hepatocellular carcinoma in a 29-year old
      bodybuilder with a history of anabolic androgenic steroid abuse: a case report.
AB  - BACKGROUND: Continuous use of anabolic androgenic steroid in high-doses is
      associated with substantial health risks, including hepatocellular adenoma.
      Malignant transformation from hepatocellular adenoma to hepatocellular carcinoma
      after anabolic androgenic steroid abuse has been rarely reported. The
      morphological distinction of adenoma from well-differentiated hepatocellular
      carcinoma is challenging and requires elaborated imaging techniques and
      histology. CASE PRESENTATION: We report about a 29-year old male professional
      bodybuilder who presented with mid-epigastric pain at the emergency unit.
      Ultrasound showed a severe hepatomegaly with multiple lesions. Contrast-enhanced
      ultrasound revealed a heterogeneous pattern with signs of hepatocellular
      carcinoma. CT scan of the abdomen confirmed multiple hypervascular lesions and
      central areas of necrosis without contrast enhancement. Subsequent diagnostics
      included fine needle aspiration (FNA) of suspicious lesions and mini-laparoscopy
      to establish the diagnosis of a beta-catenin and testosterone-receptor positive
      hepatocellular carcinoma embedded in multiple adenomas. The patient was
      subsequently treated by liver transplantation and remains tumor-free 27 month
      after surgery. CONCLUSION: Hepatocellular carcinoma occurring in association with
      anabolic androgenic steroid abuse should sensitize physicians and especially
      professional bodybuilders for the harmful use of high doses of steroids.

PMID- 25986069
TI  - Double-arc volumetric modulated therapy improves dose distribution compared to
      static gantry IMRT and 3D conformal radiotherapy for adjuvant therapy of gastric
      cancer.
AB  - BACKGROUND: The objective of this study was to compare the dose distributions of
      RapidArc (RA), static gantry intensity-modulated radiotherapy (IMRT), and three
      dimensional conformal radiotherapy (3DCRT) as adjuvant radiotherapy modalities
      for the treatment of gastric cancer. METHODS: Fifteen patients with gastric
      cancer that underwent limited lymphadenectomy of perigastric lymph nodes were
      included in this study. Dosimetric values for a total dose of 45 Gy (1.8 Gy/day)
      were calculated for the RapidArc, IMRT, and 3DCRT modalities. The following
      parameters were compared: D99%, D1%, V95%, V107%, and conformity and homogeneity
      index values (CI and HI, respectively) for the planned target volume (PTV). Dose
      volume histogram (DVH) and dose distribution of the organs at risk (OAR), as the
      maximal dose to the spinal cord, V30 and V40 of the small bowel, and V20, V30 of
      liver and kidney were also assessed respectively. RESULTS: RA, IMRT, and 3DCRT
      all achieved desirable PTV coverage. However, RA and IMRT significantly decreased
      D1% and V107%, and provided better CI and HI values compared with 3DCRT (P
      <0.05). Moreover, RA also achieved a significantly lower maximum dose for the
      spinal cord, liver V30, and kidney V20 compared to IMRT and 3DCRT; while the mean
      dose for these three organ types did not differ for the RA, IMRT, and 3DCRT
      plans. CONCLUSIONS: Both RA and IMRT achieved favorable PTV coverage compared to
      3DCRT. In addition, RA achieved better dosimetry than IMRT and 3DCRT, and
      provided better protection for the spinal cord, liver, and kidneys.

PMID- 25986068
TI  - Comparison of various SYSADOA for the osteoarthritis treatment: an experimental
      study in rabbits.
AB  - BACKGROUND: Osteoarthritis is thought to be the most prevalent chronic and
      disabling joint disease in animals and humans and its treatment is a major
      orthopaedic challenge because there is no ideal drug treatment to preserve joint
      structure and function, as well as to ameliorate the symptomatology of the
      disease. The aim of the present study was to assess, using histology,
      histomorphometry and micro-CT, the effects of the treatment with several drugs of
      the SYSADOA group and a bisphosphonate in a model of early osteoarthritis,
      comparing all the results obtained. METHODS: Osteoarthritis was surgically
      induced by anterior cruciate ligament transection and partial meniscectomy on one
      knee of 56 rabbits; treatment was started three weeks after surgery and lasted 8
      weeks; at the end of this period, the animals were sacrificed. Animals were
      divided into seven groups (8 animals each), one for each regimen of treatment
      (glucosamine sulfate, chondroitin sulfate, hyaluronic acid, diacerein,
      risedronate and a combination of risedronate and glucosamine) and one for the
      control (placebo-treated) group. Following sacrifice, femoral osteochondral
      cylinders and synovial membrane samples were obtained for their evaluation by
      qualitative and quantitative histology and micro-CT. RESULTS: The model induced
      osteoarthritic changes in the knee joints and none of the treatments showed a
      significantly better efficacy over the others. Regarding cartilage thickness and
      volume, all the treatments achieved scores halfway between control groups,
      without statistical differences. Regarding the synovial membrane, diacerein and
      risedronate showed the best anti-inflammatory profile, whereas glucosamine and
      chondroitin did not present any effect standing the hyaluronic acid results
      between the others. Regarding the subchondral bone, there were no differences in
      thickness or volume, but risedronate, diacerein and hyaluronic acid seemed to
      have considerably modified the orientation of the trabecular lattice.
      CONCLUSIONS: Out of the different drugs evaluated in the study for OA treatment,
      diacerein and risedronate showed, in all the parameters measured, a better
      profile of effectiveness; hyaluronic acid ameliorated cartilage swelling and
      promoted bone formation, but with a poor synovial effect; and finally,
      chondroitin and glucosamine sulfate prevented cartilage swelling in a similar way
      to the others, but had no effect on cartilage surface, synovial membrane or
      subchondral bone.

PMID- 25986070
TI  - Glycemic control rate of T2DM outpatients in China: a multi-center survey.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM)-associated mortality and morbidity
      are strongly dependent on glycemic control. With T2DM prevalence increasing in
      China, we aimed to assess glycemic control rates in Chinese T2DM outpatients.
      MATERIAL/METHODS: A total of 9065 adult T2DM outpatients (5035 men) were assessed
      in 26 Chinese medical centers between August 2010 and April 2012. Patients were
      stratified according to BMI (kg/m2): <24, 24-28, and >28. Successful glycemic
      control was defined as glycated hemoglobin A1c (HbA1c) <=7% or fasting plasma
      glucose (FPG) <7.0 mmol/L. RESULTS: Among the participants included in this
      study, 2939 had BMI <24, 3361 had BMI of 24-28, and 2764 had BMI >28. The
      glycemic control rate was only 32.6%, and the triple control rate for glycemia,
      blood pressure, and lipidemia was only 11.2%. Glycemic control rates by BMI group
      were 33.7% (<24), 33.8% (24-28), and 30.2% (>28) (p=0.005), and corresponding
      incidences of cardiovascular diseases (CVD) were 12.2%, 15.7%, and 15.9%
      (p<0.001). Multivariate logistic regression analysis demonstrated that older age
      (p<0.001), higher BMI (p=0.026), larger waist circumference (p<0.001), less
      education (p<0.001), and recent diagnosis (p<0.001) were independent risk factors
      for poor glycemic control. CONCLUSIONS: The T2DM glycemic control rate in China
      is currently low, especially in older obese patients with poor education and
      recent diagnosis.

PMID- 25986072
TI  - Rare genetic variants in Tunisian Jewish patients suffering from age-related
      macular degeneration.
AB  - PURPOSE: To explore the molecular basis of familial, early onset, age-related
      macular degeneration (AMD) with diverse phenotypes, using whole exome sequencing
      (WES). METHODS: We performed WES on four patients (two sibs from two families)
      manifesting early-onset AMD and searched for disease-causing genetic variants in
      previously identified macular degeneration related genes. Validation studies of
      the variants included bioinformatics tools, segregation analysis of mutations
      within the families and mutation screening in an AMD cohort of patients. RESULTS:
      The index patients were in their 50s when diagnosed and displayed a wide variety
      of clinical AMD presentations: from limited drusen in the posterior pole to
      multiple basal-laminar drusen extending peripherally. Severe visual impairment
      due to extensive geographic atrophy and/or choroidal-neovascularisation was
      common by the age of 75 years. Approximately, 400 000 genomic variants for each
      DNA sample were included in the downstream bioinformatics analysis, which ended
      in the discovery of two novel variants; in one family a single bp deletion was
      identified in the Hemicentin (HMCN1) gene (c.4162delC), whereas in the other, a
      missense variant (p.V412M) in the Complement Factor-I (CFI) gene was found.
      Screening for these variants in a cohort of patients with AMD identified another
      family with the CFI variant. CONCLUSIONS: This report uses WES to uncover rare
      genetic variants in AMD. A null-variant in HMCN1 has been identified in one AMD
      family, and a missense variant in CFI was discovered in two other families. These
      variants confirm the genetic complexity and significance of rare genetic variants
      in the pathogenesis of AMD.

PMID- 25986071
TI  - Mutations in apoptosis-inducing factor cause X-linked recessive auditory
      neuropathy spectrum disorder.
AB  - BACKGROUND: Auditory neuropathy spectrum disorder (ANSD) is a form of hearing
      loss in which auditory signal transmission from the inner ear to the auditory
      nerve and brain stem is distorted, giving rise to speech perception difficulties
      beyond that expected for the observed degree of hearing loss. For many cases of
      ANSD, the underlying molecular pathology and the site of lesion remain unclear.
      The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3,
      although the causative gene has yet to be identified. METHODS: We performed whole
      exome sequencing on DNA samples from the AUNX1 family and another small
      phenotypically similar but unrelated ANSD family. RESULTS: We identified two
      missense mutations in AIFM1 in these families: c.1352G>A (p.R451Q) in the AUNX1
      family and c.1030C>T (p.L344F) in the second ANSD family. Mutation screening in a
      large cohort of 3 additional unrelated families and 93 sporadic cases with ANSD
      identified 9 more missense mutations in AIFM1. Bioinformatics analysis and
      expression studies support this gene as being causative of ANSD. CONCLUSIONS:
      Variants in AIFM1 gene are a common cause of familial and sporadic ANSD and
      provide insight into the expanded spectrum of AIFM1-associated diseases. The
      finding of cochlear nerve hypoplasia in some patients was AIFM1-related ANSD
      implies that MRI may be of value in localising the site of lesion and suggests
      that cochlea implantation in these patients may have limited success.

PMID- 25986073
TI  - [Recognition of infections in elderly emergency patients].
AB  - BACKGROUND: Elderly patients represent an increasing population in the emergency
      department (ED) and physicians often have to deal with multimorbidity and
      complexity. Infections are one of the major reasons for ED presentations of older
      patients and the main cause of mortality; however, infections are often difficult
      to diagnose in older patients. AIM: This article provides a review of important
      indicators for infections, diagnostic tools and limitations in elderly patients.
      MATERIAL AND METHODS: A literature search was carried out using PubMed in the
      period 1990-2015 and in addition own published data are presented. RESULTS AND
      CONCLUSION: Infections in the elderly are difficult to assess in the emergency
      department due to atypical symptoms. Even subtle changes need to be recognized.
      For the diagnosis of infections in older ED patients unspecific symptoms, vital
      parameters, laboratory parameters, including C-reactive protein (CRP) and
      procalcitonin levels, cognitive function and functionality of the patient need to
      be taken into account.

PMID- 25986074
TI  - Cancer antigen-125 levels predict long-term mortality in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Cancer antigen-125 (CA-125) might be a useful biomarker to predict
      long-term mortality in patients with recent exacerbation of chronic obstructive
      pulmonary disease (COPD). METHODS: A total of 87 consecutive patients with COPD
      were evaluated prospectively. Mean age of patients was 68 +/- 10 years (55%
      males, 45% females) with a median follow-up period of 49 months. Optimal cut-off
      value of CA-125 to predict mortality was found as >93.34 U/ml, with 91%
      specificity and 40% sensitivity. RESULTS: After follow-up, 20 out of 87 (23%)
      experienced cardiovascular death. CA-125 levels were higher among those who died
      compared to those who survived [55 (12-264) versus 28 (5-245) U/ml, p = 0.013].
      In multivariate Cox proportional-hazards model with forward stepwise method, only
      CA-125 > 93.34 U/ml on admission (HR = 3.713, 95% CI: 1.035-13.323, p = 0.044)
      remained associated with an increased risk of death. CONCLUSIONS: For the first
      time, we demonstrated that CA-125 helps the risk stratification of patients with
      COPD.

PMID- 25986075
TI  - Structural and Functional Abnormalities of Carotid Artery and Their Relation with
      EVA Phenomenon.
AB  - Early vascular aging is a process characterized by a reduction in arterial
      elastin with an increase in collagen that has been related to cardiovascular risk
      factor and can determine an increased arterial stiffness and central blood
      pressure. It can be measured by several non invasive methods and in different
      arterial segment. The present paper will focus on functional (local stiffness
      parameter) and structural (intima media thickness) carotid arteries alterations
      typically evaluated by ultrasound methods. Methodological, research and clinical
      issue has been reviewed. 

PMID- 25986076
TI  - A Persian Adaptation of Medication Adherence Self-Efficacy Scale (MASES) in
      Hypertensive Patients: Psychometric Properties and Factor Structure.
AB  - INTRODUCTION: Poor adherence to anti-hypertensive treatment significantly
      contributes to the failure to achieve well-controlled blood pressure in patients
      with hypertension. AIM: To convert the original English version of Medication
      Adherence Self-efficacy Scale (MASES) into a Persian version for clinical
      application in hypertensive patients. METHODS: The backward-forward translation
      method was used to produce the Persian version of the questionnaire. Then the
      internal consistency was assessed using Cronbach's alpha. Exploratory Factor
      Analysis was applied to extract the components of the questionnaire. Correlation
      between blood pressures and drug adherence was then determined using the Persian
      MASES in hypertensive patients. RESULTS: Cronbach's alpha coefficient of the
      Persian version of MASES was >0.92, suggesting that it can yield consistent
      results. Exploratory Factor Analysis suggested an uni-dimensionality of the
      scale. Patients with uncontrolled hypertension showed poor adherence to
      hypertensive medications, therefore had significant lower self-efficacy scores
      than those with well-controlled blood pressure by medications. CONCLUSION: The
      Persian version of MASES is valid and reliable to assess self-efficacy of
      antihypertensive medication adherence in hypertensive patient, which is helpful
      to improve medication compliance in such patients in order to achieve better
      blood pressure controls.

PMID- 25986077
TI  - The Relationship Between High Pulse Pressure and Low Ankle-Brachial Index.
      Potential Utility in Screening for Peripheral Artery Disease in Population-Based
      Studies.
AB  - INTRODUCTION: The ankle-brachial index (ABI) is a reliable screening procedure
      for peripheral artery disease detection. However, ABI testing is time-consuming
      and requires trained personnel, which may preclude its routine use in population
      based surveys. Preliminary data suggest a relationship between ABI values and
      pulse pressure (PP) levels. AIM: To assess whether PP calculation might help to
      detect persons who need ABI screening in population-based studies. METHODS: All
      Atahualpa residents aged >=60 years were identified during a door-to-door survey
      and invited to undergo ABI testing. Non-consented persons and those with ABI
      >=1.4 were excluded. Using generalized linear and logistic regression models
      adjusted for demographics and cardiovascular risk factors, as well as receiver
      operator characteristics curve analysis, we evaluated the association between PP
      values and ABI, as well as the reliability of PP to identify candidates for ABI
      testing. RESULTS: Out of 239 participants (mean age 70 +/- 8 years, 62 % women),
      46 (19 %) had an ABI <=0.9 and 136 (57 %) had PP >65 mmHg, with a negative
      relationship between them (R = -0.386, p < 0.0001). A PP >65 mmHg was associated
      with an ABI <= 0.9 in the logistic regression model (OR 3.46, 95 % CI 1.07-11.2,
      p = 0.038). Continuous PP levels also correlated negatively with ABI (beta 
      0.0014, 95 % CI -0.0024 to -0.0004, p = 0.005). The sensitivity of a PP >65 mmHg
      to predict a low ABI was 85 %, and the specificity was 50 %. In contrast, the
      sensitivity of blood pressure >=140/90 mmHg was 27 % and the specificity was 10
      %. The area under the curve for the predictive value of a PP >65 mmHg was 0.673
      (95 % CI 0.609-0.736), and that of a blood pressure >=140/90 mmHg was 0.371 (95 %
      CI 0.30-0.443), with a significant difference between them (p < 0.0001).
      CONCLUSIONS: PP calculation may be a simple tool to detect candidates for ABI
      testing in population-based studies.

PMID- 25986078
TI  - Genetically Determined Platelet Reactivity and Related Clinical Implications.
AB  - Many drugs are nowadays available to inhibit platelet activation and aggregation,
      especially in patients with acute coronary syndromes and undergoing percutaneous
      coronary intervention with stent implantation. Primary targets are represented by
      enzymes or receptors involved in platelet activation. Genetic mutations in these
      targets contribute to the inter-individual variability in platelet responses
      therefore weakening the efficacy of antiplatelet agents. High on treatment
      platelet reactivity is a condition characterized by low levels of platelet
      inhibition despite the use of antiplatelet drugs. This could be responsible for
      re-infarction, stent-thrombosis and strokes, affecting short and long-term
      prognosis after coronary revascularization. So far, to test antiplatelet
      resistance either the assessment of platelet function or the identification of
      genetic carriers of poly morphisms have been pursued. Although several methods
      are now available to test platelet reactivity, it is still debated whether its
      routine assessment gives real benefits in clinical practice. The present review
      aims at examining current evidences on genetic polymorphisms affecting optimal
      platelet inhibition.

PMID- 25986080
TI  - Energy-Level Engineering at ZnO/Oligophenylene Interfaces with Phosphonate-Based
      Self-Assembled Monolayers.
AB  - We used aromatic phosphonates with substituted phenyl rings with different
      molecular dipole moments to form self-assembled monolayers (SAMs) on the Zn
      terminated ZnO(0001) surface in order to engineer the energy-level alignment at
      hybrid inorganic/organic semiconductor interfaces, with an oligophenylene as
      organic component. The work function of ZnO was tuned over a wide range of more
      than 1.7 eV by different SAMs. The difference in the morphology and polarity of
      the SAM-modified ZnO surfaces led to different oligophenylene orientation, which
      resulted in an orientation-dependent ionization energy that varied by 0.7 eV. The
      interplay of SAM-induced work function modification and oligophenylene
      orientation changes allowed tuning of the offsets between the molecular frontier
      energy levels and the semiconductor band edges over a wide range. Our results
      demonstrate the versatile use of appropriate SAMs to tune the energy levels of
      ZnO-based hybrid semiconductor heterojunctions, which is important to optimize
      its function, e.g., targeting either interfacial energy- or charge-transfer. 

PMID- 25986079
TI  - Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on
      Cardiometabolic Factors: A Multi-Center, Cross-Sectional, Clinical Study.
AB  - INTRODUCTION: Obesity is a constantly growing illness in developed countries and
      it is strictly related to cardiovascular (CV) diseases, i.e. the main cause of
      mortality throughout industralised areas. AIM: to test the ability of trained
      general physician to safely and effectively prescribe a very-low carbohydrate
      ketogenic (VLCK) diet in clinical practice, with a specific attention to the
      effect of this approach on overweight related CV risk factors (anthropometric
      measures) blood pressure, lipid levels, glucose metabolism). METHODS: The study
      has been carried out on a group of 377 patients scattered across Italy and
      monitored during 1 year. The proposed VLCK diet is a nutritional regimen
      characterized by low-fat and low- carbohydrates formulations and a protein
      content of 1.2/1.5 g/kg of ideal body weight, followed by a period of slow re
      insertion and alimentary re-education. RESULTS: All the predetermined goals
      namely safety, reduction of body weight and CV risk factors levels-have been
      reached with a significant reduction of body weight (from baseline to 4 weeks (-7
      +/- 5 kg, p < 0.001), from 4 to 12 weeks (-5 +/- 3 kg, p < 0.001), no changes
      from 12 weeks to 12 months; waistline (from baseline to 4 weeks (-7 +/- 4 cm, p <
      0.001), from 4 to 12 weeks (-5 +/- 7 cm, p < 0.001), no changes from 12 weeks to
      12 months; fatty mass (from baseline to 4 weeks (-3.8 +/- 3.8 %, p < 0.001), from
      4 to 12 weeks (-3.4 +/- 3.5 %, p < 0.001), no changes from 12 weeks to 12 months;
      SBP from baseline to 3 months (-10.5 +/- 6.4 mmHg, p < 0.001), no further changes
      after 1 year of observation). CONCLUSION: the tested VLCD diet suggested by
      trained general physicians in the setting of clinical practice seems to be able
      to significantly improve on the middle-term a number of anthropometric,
      haemodynamic and laboratory with an overall good tolerability.

PMID- 25986081
TI  - Magnetic colloidal superparticles of Co, Mn and Ni ferrite featured with comb
      type and/or linear amphiphilic polyelectrolytes; NMR and MRI relaxometry.
AB  - The ability to encapsulate hydrophobic ferrites in colloidal superparticle
      structures of an a-telechelic hexadecyl-functionalized poly(methacrylic acid)
      (C16H33-PMAA) polymer with a linear architecture was investigated and compared
      with that of two amphiphilic comb-type water-soluble copolymers, namely, P(ANa-co
      DAAm) and P(MANa-co-DMA), which are comprised of a poly(sodium acrylate) or
      poly(sodium methacrylate) backbone and pendent dodecyl acrylamide or dodecyl
      methacrylate chains, respectively. In the case of C16H33-PMAA, the pH-sensitive
      self-assembly behavior, which was studied through Nile Red probing and TEM, was
      related to its encapsulation properties. Hydrophobic MFe2O4 nanoparticles coated
      with oleylamine (MFe2O4@OAm MNPs, where M = Co, Mn, Ni) with a similar shape and
      size (~9 nm) and magnetization values of 87.4, 63.1 and 55.0 emu g(-1) for
      CoFe2O4@OAm, MnFe2O4@OAm and NiFe2O4@OAm, respectively, were successfully
      encapsulated into the hydrophobic cores of spherical micellar structures formed
      by the copolymers in an aqueous solution through a solvent mixing procedure. The
      synthesized magnetic colloidal superparticles fell in the static dephasing regime
      (SDR). NMR relaxivity measurements of MFe2O4@P(ANa-co-DAAm), MFe2O4@P(MANa-co
      DMA) and MFe2O4@C16H33-PMAA at pH = 4.5 and pH = 7 (where M = Co, Mn, Ni) at 11.7
      T were recorded and the transverse relaxivity (r2) (mM(-1) s(-1)) was determined.
      Among all, the CoFe2O4@polymers demonstrated the highest r2 relaxivity values,
      ranging from 61.6 for CoFe2O4@C16H33-PMAA (pH = 7) to 316.0 mM(-1) s(-1) for
      CoFe2O4@P(ANa-co-DAAm). The relaxation efficiency (r1 and r2) of CoFe2O4@P(ANa-co
      DAAm) was investigated further by magnetic resonance imaging (MRI) at 1.5 T and 3
      T and the r2/r1 ratios were found to be 16.5 and 18.2, respectively, indicating
      its potential use as a T2 contrast agent. 

PMID- 25986082
TI  - Automation of the in vitro micronucleus and chromosome aberration assay for the
      assessment of the genotoxicity of the particulate and gas-vapor phase of
      cigarette smoke.
AB  - Total particulate matter (TPM) and the gas-vapor phase (GVP) of mainstream smoke
      from the Reference Cigarette 3R4F were assayed in the cytokinesis-block in vitro
      micronucleus (MN) assay and the in vitro chromosome aberration (CA) assay, both
      using V79-4 Chinese hamster lung fibroblasts exposed for up to 24 h. The Metafer
      image analysis platform was adapted resulting in a fully automated evaluation
      system of the MN assay for the detection, identification and reporting of cells
      with micronuclei together with the determination of the cytokinesis-block
      proliferation index (CBPI) to quantify the treatment-related cytotoxicity. In the
      CA assay, the same platform was used to identify, map and retrieve metaphases for
      a subsequent CA evaluation by a trained evaluator. In both the assays, TPM and
      GVP provoked a significant genotoxic effect: up to 6-fold more micronucleated
      target cells than in the negative control and up to 10-fold increases in aberrant
      metaphases. Data variability was lower in the automated version of the MN assay
      than in the non-automated. It can be estimated that two test substances that
      differ in their genotoxicity by approximately 30% can statistically be
      distinguished in the automated MN and CA assays. Time savings, based on man
      hours, due to the automation were approximately 70% in the MN and 25% in the CA
      assays. The turn-around time of the evaluation phase could be shortened by 35 and
      50%, respectively. Although only cigarette smoke-derived test material has been
      applied, the technical improvements should be of value for other test substances.

PMID- 25986083
TI  - Incorporating spirituality into patient care.

PMID- 25986084
TI  - Balancing practice policies with patient needs.

PMID- 25986085
TI  - Does helping a patient find a job violate professional boundaries?

PMID- 25986086
TI  - A Friend's Request for Treatment.

PMID- 25986087
TI  - Where the rubber meets the road: the challenge of reporting colleagues' boundary
      violations.

PMID- 25986088
TI  - Professional guidelines for social media use: a starting point.

PMID- 25986089
TI  - Professional codes, public regulations, and the rebuilding of judgment following
      physicians' boundary violations.

PMID- 25986090
TI  - The need for professional standards in global health.

PMID- 25986091
TI  - Necessary boundary crossings in pediatrics.

PMID- 25986092
TI  - An Intergenerational Conversation about Frustrations, Lessons, and Hope in
      Physician Activism.

PMID- 25986093
TI  - Doctoring for the homeless: caring for the most vulnerable by building trust.

PMID- 25986094
TI  - The changing patient-physician relationship.

PMID- 25986095
TI  - Outcomes following anatomic fibular (lateral) collateral ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to investigate clinical outcomes following
      anatomic fibular (lateral) collateral ligament (FCL) reconstruction. It was
      hypothesized that anatomic FCL reconstruction would result in improved subjective
      clinical outcomes and a high patient satisfaction with outcome. METHODS: All
      patients 18 years or older who underwent FCL reconstruction from April 2010 to
      January 2013 with no other posterolateral corner pathology were included in this
      study. Patient subjective outcome scores were collected preoperatively and at a
      minimum of 2 years postoperatively. RESULTS: There were 43 patients (22 males, 21
      females, median age = 28.3 years, range 18.7-68.8) included in this study. The
      median time from injury to surgery was 22 days. Follow-up was obtained for 88 %
      of patients (n = 36) with a mean follow-up of 2.7 years. The mean Lysholm score
      significantly improved from 49 (range 11-100) to 84 (range 55-100)
      postoperatively (p < 0.001). The mean WOMAC score significantly improved from 37
      (range 3-96) to 8 (range 0-46) postoperatively (p < 0.001). The median SF-12
      physical component subscale score significantly improved from 35 (range 22-58) to
      56 (range 24-62) postoperatively (p < 0.001). The median SF-12 mental component
      subscale score did not show significant change preoperatively 54 (range 29-69) to
      postoperatively 55 (range 25-62). The median preoperative Tegner activity scale
      improved from 2 (range 0-10) to 6 (range 2-10) postoperatively (p < 0.001). The
      median patient satisfaction with outcome was 8 (range 1-10). Postoperative
      patient-reported outcome scores were not significantly different for patients who
      underwent concomitant ACL reconstruction compared to patients without ACL
      reconstruction. CONCLUSION: An anatomic FCL reconstruction with a semitendinosus
      graft significantly improved patient function and yielded high patient
      satisfaction in the 43 patients. Additionally, there was no significant
      difference in patient-reported outcomes when accounting for concomitant ACL
      reconstruction. LEVEL OF EVIDENCE: Level IV.

PMID- 25986096
TI  - Pseudoaneurysm of the articular branch of the descending genicular artery
      following double-bundle anterior cruciate ligament reconstruction.
AB  - : This report describes a case of a pseudoaneurysm of the articular branch of the
      descending genicular artery following double-bundle anterior cruciate ligament
      (ACL) reconstruction. An 18-year-old male received double-bundle ACL
      reconstruction. During ACL reconstruction, a far anteromedial portal was created
      for femoral tunnel drilling. The patient presented with pulsatile swelling on the
      medial side of the knee on the second post-operative day. The pseudoaneurysm was
      diagnosed using contrast computed tomography and Doppler ultrasonography and was
      subsequently treated by embolization with a microcatheter. Although a vascular
      injury is a very rare complication of knee arthroscopy, it should be considered a
      possibility in patients who undergo such procedures. LEVEL OF EVIDENCE: V.

PMID- 25986097
TI  - Autologous chondrocyte implantation: Is it likely to become a saviour of large
      sized and full-thickness cartilage defect in young adult knee?
AB  - PURPOSE: A literature review of the first-, second- and third-generation
      autologous chondrocyte implantation (ACI) technique for the treatment of large
      sized (>4 cm(2)) and full-thickness knee cartilage defects in young adults was
      conducted, examining the current literature on features, clinical scores,
      complications, magnetic resonance image (MRI) and histological outcomes,
      rehabilitation and cost-effectiveness. METHODS: A literature review was carried
      out in the main medical databases to evaluate the several studies concerning ACI
      treatment of large-sized and full-thickness knee cartilage defects in young
      adults. RESULTS: ACI technique has been shown to relieve symptoms and improve
      functional assessment in large-sized (>4 cm(2)) and full-thickness knee articular
      cartilage defect of young adults in short- and medium-term follow-up. Besides,
      low level of evidence demonstrated its efficiency and durability at long-term
      follow-up after implantation. Furthermore, MRI and histological evaluations
      provided the evidence that graft can return back to the previous nearly normal
      cartilage via ACI techniques. Clinical outcomes tend to be similar in different
      ACI techniques, but with simplified procedure, low complication rate and better
      graft quality in the third-generation ACI technique. CONCLUSION: ACI based on the
      experience of cell-based therapy, with the high potential to regenerate hyaline
      like tissue, represents clinical development in treatment of large-sized and full
      thickness knee cartilage defects. LEVEL OF EVIDENCE: IV.

PMID- 25986098
TI  - Long-Term Survival After Bovine Pericardial Versus Porcine Stented Bioprosthetic
      Aortic Valve Replacement: Does Valve Choice Matter?
AB  - BACKGROUND: Bioprosthetic options are increasingly used for surgical aortic valve
      replacement (AVR). However, current decision making regarding bioprosthetic valve
      choice is not data-driven given incomplete information on comparative long-term
      outcomes after stented bovine pericardial (BoAVR) vs porcine (PoAVR) AVR. As
      such, this study sought to examine the effect of bioprosthetic valve choice on
      long-term survival and reoperation after AVR. METHODS: A retrospective analysis
      of all stented bioprosthetic AVRs, with or without coronary artery bypass
      grafting procedures, at a single tertiary referral institution from 1980 to 2013
      was conducted using a prospectively maintained database. Procedures were
      classified as BoAVR or PoAVR. The effect of valve type on long-term survival was
      assessed with Kaplan-Meier analysis and a Cox proportional hazard model.
      Subanalyses stratifying by valve size and patient age at the time of AVR
      assessing mortality and reoperation were also conducted. RESULTS: We identified
      2,010 stented bioprosthetic AVR patients, comprising 1,411 BoAVRs (70.2%) and 599
      PoAVRs (29.8%), 868 (43.2%) of whom underwent concomitant coronary artery bypass
      grafting. Kaplan-Meier analysis (p = 0.12) and Cox models (hazard ratio BoAVR vs
      PoAVR, 1.08; p = 0.40) demonstrated no difference in long-term survival or need
      for reoperation after BoAVR vs PoAVR. Subanalyses of valve size and patient age
      also failed to show any association between valve choice and long-term survival
      or need for reoperation. CONCLUSIONS: For patients undergoing AVR with a stented
      bioprosthetic valve, with or without coronary artery bypass grafting, the choice
      of a porcine vs bovine pericardial bioprosthesis does not appear to affect long
      term survival or need for reoperation, regardless of valve size or patient age.
      As such, stented bioprosthetic valves would appear to be fungible, and therefore,
      valve choice should be driven by local market factors similar to other
      commodities.

PMID- 25986100
TI  - Thoracic Endovascular Aortic Repair for Challenging Aortic Arch Diseases Using
      Fenestrated Stent Grafts From Zone 0.
AB  - BACKGROUND: Although previous reports have described the repair of distal aortic
      arch aneurysms through debranching and chimney techniques, these methods
      invariably involve surgical management of the carotid artery. We report clinical
      results of thoracic endovascular aortic repair (TEVAR) using fenestrated stent
      grafts in the treatment of aortic arch aneurysms located less than 15 mm from the
      left common carotid artery. METHODS: A semi-custom-made fenestrated stent graft
      designed to fit aortic arch tortuosity and preserve blood flow at least into the
      brachiocephalic and left common carotid arteries was placed from zone 0. RESULTS:
      From 2007 through 2013, TEVAR from zone 0 was performed on 37 high-risk patients
      for open surgery (mean age 78.2 years). The mean length between the left common
      carotid artery and aortic aneurysm was 11.1 mm (range, 5 to 15 mm). The left
      subclavian artery was preserved for 26 patients (70.3%) through surgical
      reconstruction (n = 19) and graft fenestration (n = 7). The early mortality rate
      was 0%. Postoperative strokes and spinal cord ischemia occurred in 2 (5.4%) and 3
      (8.1%) patients, respectively. Although type I endoleaks at discharge were noted
      in 12 (32.4%) patients, aneurysm enlargement was noted during follow-up in 6
      (16.2%). Four patients (10.8%) underwent secondary interventions consisting of 3
      coil embolization procedures; 2 re-TEVARs and 1 open conversion. There were no
      aorta-related late deaths. Survival and aorta-related event-free rates at 2 years
      were 86.3% and 88.8%, respectively. CONCLUSIONS: Thoracic endovascular aortic
      repair using fenestrated stent graft from zone 0 can be considered as one of
      therapeutic options for high-risk patients with aortic arch diseases.

PMID- 25986099
TI  - Impact of Pulmonary Function Measurements on Long-Term Survival After Lobectomy
      for Stage I Non-Small Cell Lung Cancer.
AB  - BACKGROUND: Pulmonary function tests predict respiratory complications after
      lobectomy. We evaluated the impact of pulmonary function measurements on long
      term survival after lobectomy for stage I non-small cell lung cancer. METHODS:
      The relationship between percent predicted forced expiratory volume in 1 second
      (FEV1) and percent predicted diffusing capacity of the lung for carbon monoxide
      (Dlco) and overall survival for patients who underwent lobectomy without
      induction therapy for stage I (T1-2N0M0) non-small cell lung cancer from 1996 to
      2012 was evaluated using the Kaplan-Meier approach and a multivariable Cox
      proportional hazard model. RESULTS: During the study period, 972 patients (mean
      Dlco 76 +/- 21, mean FEV1 73 +/- 21) met inclusion criteria. Perioperative
      mortality was 2.6% (n = 25). The 5-year survival of the entire cohort was 60.1%,
      with a median follow-up of 43 months. The 5-year survival for patients with
      percent predicted FEV1 stratified by more than 80%, 61% to 80%, 41% to 60%, and
      40% or less was 70.1%, 59.3%, 52.5%, and 53.4%, respectively. The 5-year survival
      for patients with percent predicted Dlco stratified by more than 80%, 61% to 80%,
      41% to 60%, and 40% or less was 70.2%, 63.4%, 44.2%, and 33.1%, respectively. In
      multivariable survival analysis, both larger tumor size (hazard ratio 1.15, p =
      0.01) and lower Dlco (hazard ratio 0.986, p < 0.0001) were significant predictors
      of worse survival. The association of FEV1 and survival was not statistically
      significant (p = 0.18). CONCLUSIONS: Survival after lobectomy for patients with
      stage I non-small cell lung cancer is impacted by lower Dlco, which can be used
      in the risk and benefit assessment when choosing therapy.

PMID- 25986101
TI  - Nonischemic Postoperative Seizure Does Not Increase Mortality After Cardiac
      Surgery.
AB  - BACKGROUND: Postoperative seizure (PS) is an infrequent, yet distressing,
      complication after cardiac surgery. We wished to determine the prognostic
      significance of these complicated neurologic events. METHODS: The Weill Cornell
      Medical College Department of Cardiothoracic Surgery database and the New York
      State Department of Health Database were reviewed to identify all patients having
      PS after cardiac surgery between January 1, 2008, and December 31, 2011. RESULTS:
      During the study period 3,518 patients had cardiac surgery at the index hospital;
      45 of them had PS (1.27%). Overall, patients having PS had a significant increase
      in 30-day mortality when compared with those not having PS (6.7% versus 1.5%; p <
      0.006). The incidence of major postoperative complications in those having PS was
      also significantly higher (53.3% versus 10.5%; p < 0.001). However, logistic
      regression failed to demonstrate PS as an independent predictor of perioperative
      mortality. When the PS group was further stratified by the presence or absence of
      cerebrovascular accident, those having both PS and cerebrovascular accident had
      substantially increased morbidity and mortality (mortality, 0 of 33 versus 3 of
      12; major morbidity, 12 of 12 versus 12 of 33; p < 0.01 for both), whereas PS
      patients without cerebrovascular accident did not have greater risk for either
      major adverse events or mortality. CONCLUSIONS: When PS is associated with acute
      cerebrovascular accident, a significant increase in postoperative morbidity and
      mortality can be expected. However, in those with isolated PS (without evidence
      of new neurologic injury), perioperative mortality and morbidity are comparable
      to those without any neurologic complications.

PMID- 25986102
TI  - Sublocalization of Cardiac Involvement in Sarcoidosis and Surgical Exclusion in
      Patients With Congestive Heart Failure.
AB  - BACKGROUND: In sarcoidosis, cardiac involvement can cause fatal conditions such
      as left ventricular (LV) dysfunction and rhythm disturbance. We surgically
      treated critical patients with congestive heart failure due to cardiac
      sarcoidosis. METHODS: During 14 years, 384 patients with nonischemic dilated
      cardiomyopathy were operated. Among them, 14 patients (3.6%) with New York Heart
      Association (NYHA) class IV (male/female, 3/11; 57 +/- 11 years) caused by
      sarcoidosis underwent surgery (elective/emergent, 12/2). The akinetic lesion, as
      identified by speckle-tracking echocardiography, was excluded. RESULTS:
      Localization of akinetic lesions was achieved in 13 patients (93%). In the short
      axis, lesional distribution was higher in the anterior (62%) and septal segments
      (54%) when compared with the posterior (31%) and lateral segments (23%). Along
      the long axis, regional distribution was higher in the mid (85%) and apical
      segments (69%) when compared with the basal segment (31%). The main lesions were
      excluded by septal anterior ventricular exclusion (n = 5), posterior restoration
      procedure (n = 3), endoventricular circular patch plasty (n = 3), and linear
      resection (n = 2). Mitral valve surgery included mitral valve plasty (n = 7) and
      replacement (n = 7). In patients undergoing elective surgery, early results
      showed that 10 patients survived (83%) and NYHA class improved (6 patients in
      class II and 4 in class III). Patients who underwent emergent surgery did not
      survive. The observation period was 55 +/- 59 months in survivors. During follow
      up, 4 patients died after 42 +/- 48 months. The other 5 patients have survived
      for 71 +/- 61 months. The 3- and 5-year survival rates were 65% and 52%,
      respectively. CONCLUSIONS: Sarcoidosis can result in sublocalized LV involvement,
      which can be surgically excluded.

PMID- 25986103
TI  - Basic research: FGF-21 antiobesity action independent of UCP1 and WAT browning.

PMID- 25986107
TI  - Metabolism: Mechanisms of hepatic glucose production revealed.

PMID- 25986106
TI  - Nutrition: The whole cereal grain is more informative than cereal fibre.

PMID- 25986109
TI  - Obesity: Mapping metabolites--specific metabolic signatures in urine are
      associated with adiposity.

PMID- 25986108
TI  - Diabetes: Antibiotics or prodiabetics?

PMID- 25986111
TI  - ERCP (Ensuring Really Competent Practice): enough words-action please!

PMID- 25986112
TI  - Assessing fellow skills: practice what you preach, measure what you teach.

PMID- 25986113
TI  - Flute or tuba: women and publishing success in top gastroenterology journals.

PMID- 25986114
TI  - Development and evaluation of a 3D printed endoscopic ampullectomy training model
      (with video).
AB  - BACKGROUND: Endoscopic ampullectomy is a technically challenging, high-risk
      procedure with limited training opportunities. Although simulation models can
      assist with endoscopic skill acquisition, an ampullectomy model does not
      currently exist. OBJECTIVE: To develop a training model that can be used to
      improve technical skills, knowledge, and confidence in performing endoscopic
      ampullectomy. DESIGN: Experimental study. SETTING: Tertiary hospital innovation
      laboratory. SUBJECTS: Twenty-one endoscopists attending an endoscopic resection
      workshop. INTERVENTIONS: A prototype for endoscopic ampullectomy was created by
      computer-aided design and 3-dimensional printing of an ampullary mount and base
      to which a chicken heart was attached and inserted into a silicone stomach
      duodenum model. Study participants performed an ampullectomy and evaluated the
      prototype with a pre- and postampullectomy questionnaire by using a scale of 1 to
      5 (very low to very high). MAIN OUTCOME MEASUREMENTS: Evaluation of core
      procedural steps, technical and visual realism, and proceduralist technical
      knowledge and confidence. RESULTS: Sixteen endoscopists participated in the
      study. All core procedural steps were completed by 14 participants. The mean
      overall technical and visual realism scores were 3.1 (standard deviation [SD],
      0.9) and 3.2 (SD, 0.9), respectively. Ten participants (10/15, 66.7%) thought
      that their technical knowledge had improved, and 11 thought that it would
      increase further with additional sessions (11/15, 73.3%). Mean confidence score
      before and after using the model was 2.2 (SD, 1.2) and 2.9 (SD, 1.1),
      respectively (P=.132). LIMITATIONS: Pilot study, lack of follow-up of
      participants' endoscopic practice after model experience. CONCLUSION: Although
      further studies are necessary for validation, this novel prototype appears useful
      for endoscopic ampullectomy training.

PMID- 25986115
TI  - EUS-guided trans-aortic fine-needle aspiration for intra-abdominal plasmacytoma
      in a patient with multiple myeloma.

PMID- 25986116
TI  - It pays to look around.

PMID- 25986117
TI  - Incidental foreign body: watch out for the elderly.

PMID- 25986118
TI  - Development of Barrett's esophagus after total gastrectomy.

PMID- 25986119
TI  - Stenting after severe iatrogenic submucosal dissection in a patient with newly
      diagnosed eosinophilic esophagitis.

PMID- 25986120
TI  - Combined endovascular and endoscopic management of thoracic aortic
      pseudoaneurysm, mediastinal pseudocyst, and pancreatic pleural effusion due to
      chronic pancreatitis.

PMID- 25986121
TI  - CT esophagram findings after POEM procedure.

PMID- 25986122
TI  - Response.

PMID- 25986123
TI  - Antibiotic prophylaxis for GI endoscopy.

PMID- 25986124
TI  - Response.

PMID- 25986126
TI  - [Professional Association of German Neuroradiologists].

PMID- 25986125
TI  - Factors associated with daily walking of dogs.
AB  - BACKGROUND: Regular physical activity is beneficial to the health of both people
      and animals. The role of regular exercise undertaken together, such as dog
      walking, is a public health interest of mutual benefit. Exploration of barriers
      and incentives to regular dog walking by owners is now required so that effective
      interventions to promote it can be designed. This study explored a well
      characterised cross-sectional dataset of 276 dogs and owners from Cheshire, UK,
      for evidence of factors associated with the dog being walked once or more per
      day. RESULTS: Factors independently associated with daily walking included:
      number of dogs owned (multiple (vs. single) dogs negatively associated); size
      (medium and possibly large dogs (vs. small) positively associated); and number of
      people in the household (more people negatively associated). Furthermore, a
      number of factors related to the dog-owner relationship and the dog's behaviour
      were associated with daily walking, including: having acquired the dog for a
      hobby (positively associated); dog lying on furniture (positively associated);
      dog lying on laps (negatively associated); growling at household members
      (negatively associated); and playing chase games with the dog (negatively
      associated). CONCLUSIONS: These findings are consistent with the hypothesis that
      the strength and nature of the human-dog relationship incentivises dog walking,
      and that behavioural and demographic factors may affect dog walking via this
      mechanism. Future studies need to investigate how dog demographic and behavioural
      factors, plus owner behavioural factors and perceptions of the dog, influence the
      dog-human relationship in respect to the perceived support and motivation a dog
      can provide for walking.

PMID- 25986127
TI  - Process of the Functional Reorganization of the Cortical Centers for Movement in
      GBM Patients: fMRI Study.
AB  - PURPOSE: The aim of this study was to verify whether the functional
      reorganization of motor cortex is associated with the increase in the size of WHO
      type IV glioma lesion, that is, disease duration and development, and whether
      surgical treatment has an impact on cerebral plasticity. METHODS: The study
      included 16 patients with primary tumors of the brain located at the region of
      central sulcus. The clinical status of patients and tumor volume was determined.
      Functional magnetic resonance imaging examinations were performed before and 3
      months after operation. RESULTS: The activity of all cortical centers, both
      contralateral and ipsilateral, was observed in a group of small as well as large
      tumors. The intensity of activation and the number of activated clusters of small
      tumors were almost always higher as compared with the large tumors. The frequency
      of the activity of contralateral areas was similar during the first and the
      second examination. In the case of ipsilateral centers, the frequency of
      activation during the second examination was lower. Mean values of t-statistics
      during the first examination were higher than during the second examination.
      Supplementary motor area (SMAa) was the only center for which the mean values of
      activation intensity remained similar. CONCLUSIONS: SMAa seems to play the most
      important role in the processes of motor cortex plasticity in high-grade glioma
      patients. Surgery seems not having a significant influence on the pattern of
      functional reorganization of the cortical centers for movement. Identification of
      the individual patterns of the reorganization of motor centers plays an important
      role in clinical practice.

PMID- 25986130
TI  - Pre-clinical and clinical walking kinematics in female breeding pigs with
      lameness: A nested case-control cohort study.
AB  - Gait profiles were investigated in a cohort of female pigs experiencing a
      lameness period prevalence of 29% over 17 months. Gait alterations before and
      during visually diagnosed lameness were evaluated to identify the best
      quantitative clinical lameness indicators and early predictors for lameness. Pre
      breeding gilts (n= 84) were recruited to the study over a period of 6 months,
      underwent motion capture every 5 weeks and, depending on their age at entry to
      the study, were followed for up to three successive gestations. Animals were
      subject to motion capture in each parity at 8 weeks of gestation and on the day
      of weaning (28 days postpartum). During kinematic motion capture, the pigs walked
      on the same concrete walkway and an array of infra-red cameras was used to
      collect three dimensional coordinate data of reflective skin markers attached to
      the head, trunk and limb anatomical landmarks. Of 24 pigs diagnosed with
      lameness, 19 had preclinical gait records, whilst 18 had a motion capture while
      lame. Depending on availability, data from one or two preclinical motion capture
      1-11 months prior to lameness and on the day of lameness were analysed. Lameness
      was best detected and evaluated using relative spatiotemporal gait parameters,
      especially vertical head displacement and asymmetric stride phase timing.
      Irregularity in the step-to-stride length ratio was elevated (deviation  >= 0.03)
      in young pigs which presented lameness in later life (odds ratio 7.2-10.8).

PMID- 25986128
TI  - A Feedback-Insensitive Isopropylmalate Synthase Affects Acylsugar Composition in
      Cultivated and Wild Tomato.
AB  - Acylsugars are insecticidal specialized metabolites produced in the glandular
      trichomes of plants in the Solanaceae family. In the tomato clade of the Solanum
      genus, acylsugars consist of aliphatic acids of different chain lengths
      esterified to sucrose, or less frequently to glucose. Through liquid
      chromatography-mass spectrometry screening of introgression lines, we previously
      identified a region of chromosome 8 in the Solanum pennellii LA0716 genome (IL8
      1/8-1-1) that causes the cultivated tomato Solanum lycopersicum to shift from
      producing acylsucroses with abundant 3-methylbutanoic acid acyl chains derived
      from leucine metabolism to 2-methylpropanoic acid acyl chains derived from valine
      metabolism. We describe multiple lines of evidence implicating a trichome
      expressed gene from this region as playing a role in this shift. S. lycopersicum
      M82 SlIPMS3 (Solyc08g014230) encodes a functional end product inhibition
      insensitive version of the committing enzyme of leucine biosynthesis,
      isopropylmalate synthase, missing the carboxyl-terminal 160 amino acids. In
      contrast, the S. pennellii LA0716 IPMS3 allele found in IL8-1/8-1-1 encodes a
      nonfunctional truncated IPMS protein. M82 transformed with an SlIPMS3 RNA
      interference construct exhibited an acylsugar profile similar to that of IL8-1-1,
      whereas the expression of SlIPMS3 in IL8-1-1 partially restored the M82 acylsugar
      phenotype. These IPMS3 alleles are polymorphic in 14 S. pennellii accessions
      spread throughout the geographical range of occurrence for this species and are
      associated with acylsugars containing varying amounts of 2-methylpropanoic acid
      and 3-methylbutanoic acid acyl chains.

PMID- 25986129
TI  - The Impact of the Branched-Chain Ketoacid Dehydrogenase Complex on Amino Acid
      Homeostasis in Arabidopsis.
AB  - The branched-chain amino acids (BCAAs) Leu, Ile, and Val are among nine essential
      amino acids that must be obtained from the diet of humans and other animals, and
      can be nutritionally limiting in plant foods. Despite genetic evidence of its
      importance in regulating seed amino acid levels, the full BCAA catabolic network
      is not completely understood in plants, and limited information is available
      regarding its regulation. In this study, transcript coexpression analyses
      revealed positive correlations among BCAA catabolism genes in stress,
      development, diurnal/circadian, and light data sets. A core subset of BCAA
      catabolism genes, including those encoding putative branched-chain ketoacid
      dehydrogenase subunits, is highly expressed during the night in plants on a diel
      cycle and in prolonged darkness. Mutants defective in these subunits accumulate
      higher levels of BCAAs in mature seeds, providing genetic evidence for their
      function in BCAA catabolism. In addition, prolonged dark treatment caused the
      mutants to undergo senescence early and overaccumulate leaf BCAAs. These results
      extend the previous evidence that BCAAs can be catabolized and serve as
      respiratory substrates at multiple steps. Moreover, comparison of amino acid
      profiles between mature seeds and dark-treated leaves revealed differences in
      amino acid accumulation when BCAA catabolism is perturbed. Together, these
      results demonstrate the consequences of blocking BCAA catabolism during both
      normal growth conditions and under energy-limited conditions. 

PMID- 25986131
TI  - Agreement between veterinary patient data collected from different sources.
AB  - Determining the accuracy of the electronic medical record (EMR) is vital to the
      progress of practice-based research. The aim of this study was to determine the
      agreement between the EMR and other sources of signalment data. Data were
      gathered during direct observation of small animal consultations in eight
      veterinary practices. Breed, age, sex and neuter status were recorded, where
      available, from the EMR, owner and observer and then compared for agreement.
      Agreement was 'almost perfect' or 'strong' for 18/28 comparisons, although there
      was variation between the species. The results have implications for researchers
      collecting data from the EMR of first opinion practices. Future work could focus
      on the accuracy of other data obtained from the EMR. 

PMID- 25986132
TI  - Impact of three inactivated bovine viral diarrhoea virus vaccines on bulk milk
      p80 (NS3) ELISA test results in dairy herds.
AB  - Bovine viral diarrhoea virus (BVDV) is endemic in many countries and vaccines are
      used as a component of control and eradication strategies. Surveillance
      programmes to detect exposure to BVDV often incorporate the use of bulk milk (BM)
      testing for antibodies against BVDV p80 (NS3), but vaccination can interfere with
      these results. The aim of this study was to evaluate whether BVDV vaccines would
      confound BM testing for specific antibodies in a nationally representative group
      of commercial dairy farms in the Republic of Ireland. A total of 256 commercial
      dairy herds were included in the statistical analysis. Quarterly BM or serum
      samples from selected weanling heifers (unvaccinated homeborn youngstock) were
      assessed by ELISA for antibodies against the BVDV p80 subunit and whole virus.
      Wilcoxon rank-sum and receiver operating characteristic (ROC) analyses were used
      to examine differences among groups vaccinated with one of three commercially
      available inactivated BVDV vaccines. Two of the three vaccines showed evidence of
      interference with ELISA testing of BM samples. ROC analysis highlighted that one
      vaccine did not reduce the discriminatory power of the BVDV p80 ELISA for
      identification of herds with evidence of recent BVDV circulation, when compared
      with unvaccinated herds; thus, administration of this vaccine would allow
      uncomplicated interpretation of BM ELISA test results in vaccinated seropositive
      herds. Seasonal differences in BM antibody results were identified, suggesting
      that the latter half of lactation is the most suitable time for sampling dairy
      herds containing predominantly spring calving cows. The results of the present
      study are likely to prove useful in countries allowing vaccination during or
      following BVDV eradication, where BM testing is required as part of the
      surveillance strategy. 

PMID- 25986133
TI  - Temporal and concentration effects of isoflurane anaesthesia on intestinal tissue
      oxygenation and perfusion in horses.
AB  - The aim of this study was to assess the effect of duration of anaesthesia and
      concentration of isoflurane on global perfusion as well as intestinal
      microperfusion and oxygenation. Nine Warmblood horses were premedicated with
      xylazine; anaesthesia was induced with midazolam and ketamine, and maintained
      with isoflurane. Horses were ventilated to normocapnia. During 7 h of
      anaesthesia, mean arterial blood pressures (MAP), heart rate, central venous
      pressure, pulmonary artery pressure, expiratory isoflurane concentration (ETIso)
      and cardiac output using lithium dilution were measured; cardiac index (CI) was
      calculated. Intestinal microperfusion and oxygenation were measured using laser
      Doppler flowmetry and white-light spectrophotometry. Surface probes were placed
      via median laparotomy on the serosal and mucosal site of the jejunum and the
      pelvic flexion of the colon. After 3 h of constant ETIso (1.4%), ETIso was
      increased in 0.2% increments up to 2.4%, followed by a decrease to 1.2% and an
      increase to 1.4%. The CI and MAP decreased continuously with increasing ETIso to
      40 +/- 5 mL/kg/min and 52 +/- 8 mmHg, respectively. Microperfusion and
      oxygenation remained unchanged until an ETIso of 2.0% resulted in CI and MAP of
      48 +/- 5 mL/kg/min and 62 +/- 6 mmHg, respectively, and then decreased rapidly.
      When ETIso decreased back to baseline, CI, MAP, microperfusion and oxygenation
      recovered to baseline. Isoflurane concentration but not duration of isoflurane
      anaesthesia influenced central and intestinal oxygenation and perfusion in
      healthy horses. Under isoflurane, intestinal perfusion appeared to be preserved
      until a threshold MAP or blood flow was reached.

PMID- 25986134
TI  - Quantifying the Incremental and Aggregate Cost of Missed Workdays in Adults with
      Diabetes.
AB  - OBJECTIVE: Although the national cost of missed workdays associated with diabetes
      has been estimated previously, we use the most recent available national data and
      methodology to update the individual and national estimates for the U.S
      population. METHODS: We identified 14,429 employed individuals >= 18 years of age
      in 2011 Medical Expenditure Panel Survey (MEPS) data. Diabetes and missed
      workdays were based on self-report, and cost was based on multiplying the daily
      wage rate for each individual by the number of missed days. Adjusted total
      national burden of missed workdays associated with diabetes was calculated using
      a novel two-part model to simultaneously estimate the association of diabetes
      with the number and cost of missed workdays. RESULTS: The unadjusted annual mean
      2011 cost of missed workdays was $277 (95 % CI 177.0-378.0) for individuals with
      diabetes relative to $160 (95 % CI $130-$189) for those without. The incremental
      cost of missed workdays associated with diabetes was $120 (95 % CI $30.7-$209.1).
      Based on the US population in 2011, the unadjusted national burden of missed
      workdays associated with diabetes was estimated to be $2.7 billion, while the
      fully adjusted incremental national burden was estimated to be $1.1 billion.
      CONCLUSIONS: We provide more precise estimates of the cost burden of diabetes due
      to missed workdays on the U.S population. The high incremental and total cost
      burden of missed workdays among Americans with diabetes suggests the need for
      interventions to improve diabetes care management among employed individuals.

PMID- 25986135
TI  - Underuse and Overuse of Osteoporosis Screening in a Regional Health System: a
      Retrospective Cohort Study.
AB  - BACKGROUND: The United States Preventive Services Task Force (USPSTF) recommends
      screening for osteoporosis with dual-energy x-ray absorptiometry (DXA) for women
      aged >= 65 years and younger women with increased risk. "Choosing Wisely"
      initiatives advise avoiding DXA screening in women younger than 65 years without
      osteoporosis risk factors. OBJECTIVE: We aimed to determine the extent to which
      DXA screening is used in accordance with USPSTF recommendations within a regional
      health system. DESIGN: This was a retrospective longitudinal cohort study within
      13 primary care clinics in the Sacramento, CA region. PATIENTS: The study
      included 50,995 women aged 40-85 years without prior osteoporosis screening,
      diagnosis, or treatment attending primary care visits from 2006 to 2012, observed
      for a mean of 4.4 years. MAIN MEASURES: We examined incidence of DXA screening.
      Covariates included age, race/ethnicity, and osteoporosis risk factors (body mass
      index < 20, glucocorticoid use, secondary osteoporosis, prior high-risk facture,
      rheumatoid arthritis, alcohol abuse, and current smoking). KEY RESULTS: Among
      previously unscreened women for whom the USPSTF recommends screening, 7-year
      cumulative incidence of DXA screening was 58.8 % among women aged 60-64 years
      with >= 1 risk factor (95 % CI: 51.9-65.8 %), 57.8 % for women aged 65-74 years
      (95 % CI: 55.6-60.0 %), and 42.7 % for women aged >= 75 years (95 % CI: 38.7-46.7
      %). Among women for whom the USPSTF does not recommend screening, 7-year
      cumulative incidence was 45.5 % among women aged 50-59 years (95 % CI 44.1-46.9
      %) and 58.6 % among women aged 60-64 years without risk factors (95 % CI 55.9
      61.4 %). CONCLUSIONS: DXA screening was underused in women at increased fracture
      risk, including women aged >= 65 years. Meanwhile, DXA screening was common among
      women at low fracture risk, such as younger women without osteoporosis risk
      factors. Interventions may be needed to augment the value of population screening
      for osteoporosis.

PMID- 25986136
TI  - The Effect of a Care Transition Intervention on the Patient Experience of Older
      Multi-Lingual Adults in the Safety Net: Results of a Randomized Controlled Trial.
AB  - BACKGROUND: The Hospital Consumer Assessment of Healthcare Providers and Systems
      (HCAHPS) and Care Transitions Measure (CTM-3) scores are patient experience
      measures used to determine hospital value-based purchasing reimbursement.
      Interventions to improve 30-day readmissions have met with mixed results, but
      less is known about their potential to improve the patient experience among older
      ethnically and linguistically diverse adults receiving care at safety-net
      hospitals. In this study, we assessed the effect of a nurse-led hospital-based
      care transition intervention on discharge-related patient experience in an older
      multilingual population of adults hospitalized at a safety-net hospital. METHODS:
      We randomized 700 inpatients aged 55 and older at an academic urban safety-net
      hospital. In addition to usual care, intervention participants received inpatient
      visits by a language-concordant study nurse and post-discharge phone calls from a
      language-concordant nurse practitioner to reinforce the care plan and to address
      acute complaints. We measured HCAHPS nursing, medication, and discharge
      communication domain scores and CTM-3 scores at 30 days after hospital discharge.
      RESULTS: Of 685 participants who survived to 30 days, 90 % (n = 616) completed
      follow-up interviews. The mean age was 66.2 years; over half (54.2 %) of the
      participants had cognitive impairment, and 33.8 % had moderate to severe
      depression. The majority (62.1 %) of interviews were conducted in English; 23.3 %
      were conducted in Chinese and 14.6 % in Spanish. Study nurses spent an average of
      157 min with intervention participants. Between intervention and usual care
      participants, CTM-3 scores (80.5 % vs 78.5 %; p = 0.18) and HCAHPS discharge
      communication domain scores (74.8 % vs 68.7 %; p = 0.11) did not differ, nor did
      HCAHPS scores in medication (44.5 % vs 53.1 %; p = 0.13) and nursing domains
      (67.9 % vs 64.9 %; p = 0.43). When stratified by language, no significant
      differences were seen. CONCLUSION: An inpatient standalone transition-of-care
      intervention did not improve patient discharge experience. Older multi-lingual
      and cognitively impaired populations may require higher-intensity interventions
      post-hospitalization to improve discharge experience outcomes.

PMID- 25986137
TI  - The Effectiveness of a Physician-Only and Physician-Patient Intervention on
      Colorectal Cancer Screening Discussions Between Providers and African American
      and Latino Patients.
AB  - BACKGROUND: Physician recommendation of colorectal cancer (CRC) screening is a
      critical facilitator of screening completion. Providing patients a choice of
      screening options may increase CRC screening completion, particularly among
      racial and ethnic minorities. OBJECTIVE: Our purpose was to assess the
      effectiveness of physician-only and physician-patient interventions on increasing
      rates of CRC screening discussions as compared to usual care. DESIGN: This study
      was quasi-experimental. Clinics were allocated to intervention or usual care;
      patients in intervention clinics were randomized to receipt of patient
      intervention. PARTICIPANTS: Patients aged 50 to 75 years, due for CRC screening,
      receiving care at either a federally qualified health care center or an academic
      health center participated in the study. INTERVENTION: Intervention physicians
      received continuous quality improvement and communication skills training.
      Intervention patients watched an educational video immediately before their
      appointment. MAIN MEASURES: Rates of patient-reported 1) CRC screening
      discussions, and 2) discussions of more than one screening test. KEY RESULTS: The
      physician-patient intervention (n = 167) resulted in higher rates of CRC
      screening discussions compared to both physician-only intervention (n = 183; 61.1
      % vs.50.3 %, p = 0.008) and usual care (n = 153; 61.1 % vs. 34.0 % p = 0.03).
      More discussions of specific CRC screening tests and discussions of more than one
      test occurred in the intervention arms than in usual care (44.6 % vs. 22.9 %,p =
      0.03) and (5.1 % vs. 2.0 %, p = 0.036), respectively, but discussion of more than
      one test was uncommon. Across all arms, 143 patients (28.4 %) reported discussion
      of colonoscopy only; 21 (4.2 %) reported discussion of both colonoscopy and stool
      tests. CONCLUSIONS: Compared to usual care and a physician-only intervention, a
      physician-patient intervention increased rates of CRC screening discussions, yet
      discussions overwhelmingly focused solely on colonoscopy. In underserved patient
      populations where access to colonoscopy may be limited, interventions encouraging
      discussions of both stool tests and colonoscopy may be needed.

PMID- 25986138
TI  - Validation of Self-Administered Single-Item Screening Questions (SISQs) for
      Unhealthy Alcohol and Drug Use in Primary Care Patients.
AB  - BACKGROUND: Very brief single-item screening questions (SISQs) for alcohol and
      other drug use can facilitate screening in health care settings, but are not
      widely used. Self-administered versions of the SISQs could ease barriers to their
      implementation. OBJECTIVE: We sought to validate SISQs for self-administration in
      primary care patients. DESIGN: Participants completed SISQs for alcohol and drugs
      (illicit and prescription misuse) on touchscreen tablet computers. Self-reported
      reference standard measures of unhealthy use, and more specifically of risky
      consumption, problem use, and substance use disorders, were then administered by
      an interviewer, and saliva drug tests were collected. PARTICIPANTS: Adult
      patients aged 21-65 years were consecutively enrolled from two urban safety-net
      primary care clinics. MAIN MEASURES: The SISQs were compared against reference
      standards to determine sensitivity, specificity, and area under the receiver
      operating characteristic curve (AUC) for alcohol and drug use. KEY RESULTS: Among
      the 459 participants, 22 % reported unhealthy alcohol use and 25 % reported drug
      use in the past year. The SISQ-alcohol had sensitivity of 73.3 % (95 % CI 65.3
      80.3) and specificity of 84.7 % (95 % CI 80.2-88.5), AUC = 0.79 (95 % CI 0.75
      0.83), for detecting unhealthy alcohol use, and sensitivity of 86.7 % (95 % CI
      75.4-94.1) and specificity of 74.2 % (95 % CI 69.6-78.4), AUC = 0.80 (95 % CI
      0.76-0.85), for alcohol use disorder. The SISQ-drug had sensitivity of 71.3 % (95
      % CI 62.4-79.1) and specificity of 94.3 % (95 % CI 91.3-96.6), AUC = 0.83 (95 %
      CI 0.79-0.87), for detecting unhealthy drug use, and sensitivity of 85.1 (95 % CI
      75.0-92.3) and specificity of 88.6 % (95 % CI 85.0-91.6), AUC = 0.87 (95 % CI
      0.83-0.91), for drug use disorder. CONCLUSIONS: The self-administered SISQs are a
      valid approach to detecting unhealthy alcohol and other drug use in primary care
      patients. Although self-administered SISQs may be less accurate than the
      previously validated interviewer-administered versions, they are potentially
      easier to implement and more likely to retain their fidelity in real-world
      practice settings.

PMID- 25986140
TI  - Statins and Diabetes: The Plot Thickens.

PMID- 25986139
TI  - Hospitalization-Associated Disability in Adults Admitted to a Safety-Net
      Hospital.
AB  - BACKGROUND: Little is known about hospitalization-associated disability (HAD) in
      older adults who receive care in safety-net hospitals. OBJECTIVES: To describe
      HAD and to examine its association with age in adults aged 55 and older
      hospitalized in a safety-net hospital. DESIGN: Secondary post hoc analysis of a
      prospective cohort from a discharge intervention trial, the Support from Hospital
      to Home for Elders. SETTING: Medicine, cardiology, and neurology inpatient
      services of San Francisco General Hospital, a safety-net hospital. PARTICIPANTS:
      A total of 583 participants 55 and older who spoke English, Spanish, or Chinese.
      We determined the incidence of HAD 30 days post-hospitalization and ORs for HAD
      by age group. MEASUREMENTS: The outcome measure was death or HAD at 30 days after
      hospital discharge. HAD is defined as a new or additional disability in one or
      more activities of daily living (ADL) that is present at hospital discharge
      compared to baseline. Participants' functional status at baseline (2 weeks prior
      to admission) and 30 days post-discharge was ascertained by self-report of ADL
      function. RESULTS: Many participants (75.3 %) were functionally independent at
      baseline. By age group, HAD occurred as follows: 27.4 % in ages 55-59, 22.2 % in
      ages 60-64, 17.4 % in ages 65-69, 30.3 % in ages 70-79, and 61.7 % in ages 80 or
      older. Compared to the youngest group, only the adjusted OR for HAD in adults
      over 80 was significant, at 2.45 (95 % CI 1.17, 5.15). CONCLUSIONS: In adults at
      a safety-net hospital, HAD occurred in similar proportions among adults aged 55
      59 and those aged 70-79, and was highest in the oldest adults, aged >= 80. In
      safety-net hospitals, interventions to reduce HAD among patients 70 years and
      older should consider expanding age criteria to adults as young as 55.

PMID- 25986141
TI  - On Ghosts and Other Unwelcome Guests.

PMID- 25986142
TI  - Capsule Commentary on Silverman et al., The Relationship Between Food Insecurity
      and Depression, Diabetes Distress and Medication Adherence Among Low-Income
      Patients with Poorly Controlled Diabetes.

PMID- 25986143
TI  - Personalizing Diabetes Prevention: Is it Time to Focus on the Intervention?

PMID- 25986144
TI  - Construction of an infectious clone of a plant RNA virus in a binary vector using
      one-step Gibson Assembly.
AB  - The construction of full-length infectious clones of RNA viruses is often
      laborious due to the many cloning steps required and the DNA exclusion within the
      plasmid during Escherichia coli transformation. We demonstrate single-step
      cloning procedure of an infectious cDNA of the tomato blistering mosaic virus
      (ToBMV) using Gibson Assembly (GA), which drastically reduces the number of
      cloning steps. By agro-inoculation with the construct obtained by this procedure,
      ToBMV was recovered six days post-inoculation in Nicotiana benthamiana plants.
      The symptoms induced by the recovered virus were indistinguishable from those
      caused by the wild-type virus. We conclude that the GA is very useful method
      particularly to construct a full-length cDNA clone of a plant RNA virus in a
      binary vector. 

PMID- 25986145
TI  - Warfarin Metabolites in Patients Following Cardiac Valve Implantation: A
      Contribution of Clinical and Genetic Factors.
AB  - INTRODUCTION: Warfarin, a racemic mixture of S- and R-enantiomers, is the
      cornerstone of therapy in patients following cardiac valve replacement. S
      warfarin is metabolized to 7-S-hydroxywarfarin by the cytochrome P450 isoform 2C9
      encoded by CYP2C9 gene. R-warfarin is metabolized by multiple cytochromes P450.
      We sought to assess the impact of clinical and genetic factors on circulating
      warfarin metabolites following valve implantation. MATERIAL AND METHODS: Venous
      blood was collected from 120 patients after 3 months since elective mitral and/or
      aortic valve replacement. Plasma S-warfarin, R-warfarin, S-7-hydroxywarfarin, and
      R-7-hydroxywarfarin were determined using high-performance liquid chromatography.
      The S-7-hydroxywarfarin/S-warfarin and S-warfarin/R-warfarin (S/R) ratios, along
      with warfarin sensitivity index (WSI), defined as INR/S-warfarin ratio, were
      calculated. Vitamin K epoxide reductase complex subunit 1 (VKORC1) c.-1639A,
      CYP2C9*3 and CYP2C9*2 alleles were determined using real-time polymerase chain
      reaction. RESULTS: The S-warfarin was higher in former smokers (p = 0.047) and
      the VKORC1 c.-1639A allele carriers (p < 0.0001). The S-7-hydroxywarfarin was
      lower in carriers of the VKORC1 c.-1639A allele (p = 0.0005) and CYP2C9*3 (p =
      0.047). The S-7-hydroxywarfarin/S-warfarin ratio was lower in the carriers of
      CYP2C9*3 (p = 0.008), but not in those with VKORC1 -c.1639A allele. The S/R ratio
      was higher in patients with hypertension (p = 0.01). The independent predictors
      of elevated S/R ratio defined as the upper quartile were diabetes (p = 0.045),
      CYP2C9*3 (p < 0.0001) and CYP2C9*2 (p = 0.0002). The independent predictors of
      elevated WSI were current smoking (p = 0.049), implantation of mechanical valve
      (p = 0.006) and VKORC1c.-1639A allele (p = 0.007). CONCLUSION: We conclude that
      not only genetic, but also several clinical factors affect warfarin metabolites
      in patients following cardiac valve implantation.

PMID- 25986146
TI  - Ivabradine prolongs phase 3 of cardiac repolarization and blocks the hERG1
      (KCNH2) current over a concentration-range overlapping with that required to
      block HCN4.
AB  - In Europe, ivabradine has recently been approved to treat patients with angina
      who have intolerance to beta blockers and/or heart failure. Ivabradine is
      considered to act specifically on the sinoatrial node by inhibiting the If
      current (the funny current) to slow automaticity. However, in vitro studies show
      that ivabradine prolongs phase 3 repolarization in ventricular tissue. No
      episodes of Torsades de Pointes have been reported in randomized clinical
      studies. The objective of this study is to assess whether ivabradine blocked the
      hERG1 current. In the present study we discovered that ivabradine prolongs action
      potential and blocks the hERG current over a range of concentrations overlapping
      with those required to block HCN4. Ivabradine produced tonic, rather than use
      dependent block. The mutation Y652A significantly suppressed pharmacologic block
      of hERG by ivabradine. Disruption of C-type inactivation also suppressed block of
      hERG1 by ivabradine. Molecular docking and molecular dynamics simulations
      indicate that ivabradine may access the inner cavity of the hERG1 via a
      lipophilic route and has a well-defined binding site in the closed state of the
      channel. Structural organization of the binding pockets for ivabradine is
      discussed. Ivabradine blocks hERG and prolongs action potential duration. Our
      study is potentially important because it indicates the need for active post
      marketing surveillance of ivabradine. Importantly, proarrhythmia of a number of
      other drugs has only been discovered during post marketing surveillance. 

PMID- 25986148
TI  - Mechanical stretch enhances the expression and activity of osteopontin and MMP-2
      via the Akt1/AP-1 pathways in VSMC.
AB  - Hemodynamic forces causing mechanical stretch (MS) of vascular smooth muscle
      cells (VSMC) play an important role in vascular remodeling, but the underlying
      mechanism involved is not fully understood. Thus, this study investigated whether
      osteopontin (OPN) expression in VSMC was induced by MS, and identified the
      intracellular signaling pathways involved in OPN production. The plasma level of
      OPN and its expression in aortic tissue were increased in various animal models
      of hypertension including spontaneous hypertensive rats and hypertensive mice
      induced by angiotensin II or L-NAME. When aortic VSMC was stimulated with MS, OPN
      production was increased, which was markedly attenuated in VSMC treated with
      PI3K/Akt inhibitor as well as in Akt1-depleted cells, but not in Akt2-depleted
      cells, suggesting a pivotal role of Akt1 isoform in OPN expression in VSMC. In
      the promoter assay, MS increased OPN promoter activity, which was attenuated when
      the region harboring AP-1 binding sites was mutated. The MS-enhanced promoter
      activity and OPN expression were also decreased in cells treated with AP-1 siRNA
      or inhibitor. Moreover, MS-induced MMP-2 production was attenuated in cells
      treated with OPN siRNA or anti-OPN antibody as well as in OPN-deficient VSMC
      cultured from aorta of OPN deficient mice. In in vivo experiments, the
      expressions of OPN and MMP-2 were increased in the aortic tissues from
      hypertensive mice, but these increases were markedly attenuated in OPN-deficient
      mice with hypertension. In conclusion, these results suggested that OPN
      expression in the hypertensive vasculature was increased via signaling pathways
      that involve Akt1/AP-1, leading to vascular remodeling by increasing the
      production of MMP-2. 

PMID- 25986147
TI  - Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle
      progression for cardiac septation.
AB  - RATIONALE: Mutations of TBX5 cause Holt-Oram syndrome (HOS) in humans, a disease
      characterized by atrial or occasionally ventricular septal defects in the heart
      and skeletal abnormalities of the upper extremity. Previous studies have
      demonstrated that Tbx5 regulates Osr1 expression in the second heart field (SHF)
      of E9.5 mouse embryos. However, it is unknown whether and how Tbx5 and Osr1
      interact in atrial septation. OBJECTIVE: To determine if and how Tbx5 and Osr1
      interact in the posterior SHF for cardiac septation. METHODS AND RESULTS: In the
      present study, genetic inducible fate mapping showed that Osr1-expressing cells
      contribute to atrial septum progenitors between E8.0 and E11.0. Osr1 expression
      in the pSHF was dependent on the level of Tbx5 at E8.5 and E9.5 but not E10.5,
      suggesting that the embryo stage before E10.5 is critical for Tbx5 interacting
      with Osr1 in atrial septation. Significantly more atrioventricular septal defects
      (AVSDs) were observed in embryos with compound haploinsufficiency for Tbx5 and
      Osr1. Conditional compound haploinsufficiency for Tbx5 and Osr1 resulted in a
      significant cell proliferation defect in the SHF, which was associated with fewer
      cells in the G2 and M phases and a decreased level of Cdk6 expression.
      Remarkably, genetically targeted disruption of Pten expression in atrial septum
      progenitors rescued AVSDs caused by Tbx5 and Osr1 compound haploinsufficiency.
      There was a significant decrease in Smo expression, which is a Hedgehog (Hh)
      signaling pathway modulator, in the pSHF of Osr1 knockout embryos at E9.5,
      implying a role for Osr1 in regulating Hh signaling. CONCLUSIONS: Tbx5 and Osr1
      interact to regulate posterior SHF cell cycle progression for cardiac septation.

PMID- 25986149
TI  - International Classification of Headache Disorders 3rd edition beta-based field
      testing of vestibular migraine in China: Demographic, clinical characteristics,
      audiometric findings and diagnosis statues.
AB  - OBJECTIVES: This study explored the clinical characteristics of vestibular
      migraine in Chinese subjects and performed a field test of the criteria of the
      International Classification of Headache Disorders 3rd edition beta version.
      METHODS: Consecutive patients with vestibular migraine were surveyed and
      registered in a headache clinic during the study period. The diagnosis of
      vestibular migraine was made according to International Classification of
      Headache Disorders 3rd edition beta version. Assessments included standardized
      neuro-otology bedside examination, pure-tone audiogram, bithermal caloric
      testing, neurological imaging, cervical X-ray or magnetic resonance imaging,
      Doppler ultrasound of cerebral arteries and laboratory tests. RESULTS: A total of
      67 patients (62 female/five male, 47.8 +/- 10.3 years old) were enrolled in this
      study. The mean ages of migraine and vertigo onset were 32.2 +/- 11.5 and 37.9 +/
      10.1 years, respectively. The most common migraine subtype was migraine without
      aura (79%), followed by migraine with aura (12%) and chronic migraine (9%). The
      duration of vertigo attacks varied from seconds to days and 25% of patients had
      attacks that lasted less than 5 minutes. Among the patients with short-lasting
      attacks, 75% of these patients had >=5 attacks per day within 72 hours. Auditory
      symptoms were reported in 36% of the patients. Migraine prophylactic treatments
      were effective in 77% of the patients. CONCLUSIONS: Our study showed that the
      clinical features of vestibular migraine in China were similar to those of
      Western studies. The definition of vertigo episodes and migraine subtypes of
      vestibular migraine in International Classification of Headache Disorders 3rd
      edition beta version might be modified further. More than five vertigo attacks
      per day within 72 hours might be helpful as far as identifying vestibular
      migraine patients with short-lasting attacks.

PMID- 25986151
TI  - Survival in patients with colorectal cancer diagnosed by screening colonoscopy.
AB  - BACKGROUND: In Germany, screening colonoscopy was first established in 2002 as
      part of the national cancer screening program. OBJECTIVE: To evaluate whether
      colorectal cancer (CRC) survival differs when CRC is diagnosed by screening
      colonoscopy (S-CRC) versus diagnostic colonoscopy (D-CRC). DESIGN: Long-term,
      retrospective, multicenter, observational study. SETTING: Study centers: 10
      private gastroenterology practices in Germany. PATIENTS: A total of 60 patients
      diagnosed with CRC during screening colonoscopy and 252 patients during
      diagnostic colonoscopy in 2002, 2003, and 2004. INTERVENTIONS: Colonoscopy. MAIN
      OUTCOME MEASUREMENTS: Survival of patients up to December 2013. RESULTS: Mean (+/
      standard deviation [SD]) follow-up time was 81.0 (+/- 40.1) months. Union
      Internationale Contre le Cancer (UICC) stages I and II were found more often in S
      CRC (81.6%) compared with D-CRC (59.9%; P < .002). Kaplan-Meier analysis showed
      significantly reduced overall survival for patients with D-CRC (mean [+/- SD]
      86.9 [+/- 3.0] months; 95% confidence interval [CI], 81.0-92.8) compared with S
      CRC (mean [+/- SD] 107.1 [+/- 4.9] months; 95% CI, 97.4-116.9; P = .003). When
      deaths not related to CRC were excluded, survival was still shorter for D-CRC
      patients (mean [+/- SD] 89.4 [+/- 3.0] months; 95% CI, 83.5-95.4) compared with S
      CRC (mean [+/- SD] 109.6 [+/- 4.7] months; 95% CI, 100.2-119.0; P = .004).
      LIMITATIONS: Retrospective study design. CONCLUSION: In this long-term,
      retrospective study, patients with CRC diagnosed during screening colonoscopy
      lived significantly longer when compared with patients with CRC diagnosed during
      diagnostic colonoscopy.

PMID- 25986150
TI  - Multiple chaperonins in bacteria--novel functions and non-canonical behaviors.
AB  - Chaperonins are a class of molecular chaperones that assemble into a large double
      ring architecture with each ring constituting seven to nine subunits and
      enclosing a cavity for substrate encapsulation. The well-studied Escherichia coli
      chaperonin GroEL binds non-native substrates and encapsulates them in the cavity
      thereby sequestering the substrates from unfavorable conditions and allowing the
      substrates to fold. Using this mechanism, GroEL assists folding of about 10-15 %
      of cellular proteins. Surprisingly, about 30 % of the bacteria express multiple
      chaperonin genes. The presence of multiple chaperonins raises questions on
      whether they increase general chaperoning ability in the cell or have developed
      specific novel cellular roles. Although the latter view is widely supported,
      evidence for the former is beginning to appear. Some of these chaperonins can
      functionally replace GroEL in E. coli and are generally indispensable, while
      others are ineffective and likewise are dispensable. Additionally, moonlighting
      functions for several chaperonins have been demonstrated, indicating a functional
      diversity among the chaperonins. Furthermore, proteomic studies have identified
      diverse substrate pools for multiple chaperonins. We review the current
      perception on multiple chaperonins and their physiological and functional
      specificities.

PMID- 25986153
TI  - Health Disparities in Ischaemic Heart Disease Mortality in Hungary From 1970 to
      2010: An Age-Period-Cohort Analysis.
AB  - BACKGROUND: The objective of this study was to examine long-term trends in rates
      of ischaemic heart disease (IHD) mortality, a leading cause of mortality in
      Hungary. The study examined the effects of age, period, and cohort on IHD
      mortality rates and compared mortality rates between the capital (Budapest) and
      non-capital counties. METHODS: Data on IHD deaths and population censuses were
      obtained from the Hungarian Central Statistical Office. Age-period-cohort
      analysis utilized nine age-group classes for ages 40 to 84 years, eight time
      periods from 1970 to 2009, and 16 birth cohorts from 1886 to 1969. RESULTS: Age
      adjusted IHD mortality rates for men and for women generally increased from 1970
      to 1993 and from 1980 to 1999, respectively, decreasing thereafter for both
      sexes. IHD mortality rates for men and for women from Budapest were lower from
      1991 and from 1970, respectively, than corresponding rates in non-capital
      counties, with the difference increasing after 1999. Age had a more significant
      influence on mortality rates for women than for men. The period effect increased
      from 1972 to 1982 and decreased thereafter for men, while the period effect
      decreased consistently for women from 1972 to 2007. The decline in period effect
      for both sexes was larger for individuals from the capital than for those from
      non-capital counties. The cohort effect for both sexes declined from birth years
      1890 to 1965, with a steeper decline for individuals from the capital than for
      those from non-capital counties. CONCLUSIONS: The findings indicate a need for
      programs in Hungary for IHD prevention, especially for non-capital counties.

PMID- 25986152
TI  - Global Call to Action to scale-up coverage of intermittent preventive treatment
      of malaria in pregnancy: seminar report.
AB  - In 2014, a global 'Call to Action' seminar for the scale-up of intermittent
      preventive treatment of malaria in pregnancy was held during the 63rd Annual
      Meeting of the American Society of Tropical Medicine and Hygiene. This report
      summarizes the presentations and main discussion points from the meeting. 

PMID- 25986154
TI  - Trends of Underweight and Overweight/Obesity Among Japanese Schoolchildren From
      2003 to 2012, Defined by Body Mass Index and Percentage Overweight Cutoffs.
AB  - BACKGROUND: We investigated the prevalence and trends of underweight and
      overweight/obesity in a population-based sample of Japanese schoolchildren from
      2003 to 2012, defined by body mass index (BMI) and percentage overweight (POW).
      METHODS: Subjects comprised fourth and seventh graders from the town of Ina,
      Japan, from 2003 to 2012. The height and weight of each subject were measured.
      Children were classified as underweight, normal weight, or overweight/obese using
      two criteria: BMI cutoff points proposed by the International Obesity Task Force
      and cutoffs based on POW in Japan. RESULTS: Data from 4367 fourth graders and
      3724 seventh graders were analyzed. The prevalence of underweight and overweight
      as defined by POW criteria were lower than those based on BMI criteria. There was
      a decrease in the prevalence of overweight among fourth-grade boys and girls and
      seventh-grade girls according to BMI; this decrease was also observed when POW
      criteria were used for the definition of overweight. CONCLUSIONS: The prevalence
      and trends of both underweight and overweight as defined by POW were
      underestimated among Japanese schoolchildren compared to those determined using
      BMI. The results of this study also suggest that trends in underweight and
      overweight/obesity using POW criteria are similar to those based on BMI criteria
      among schoolchildren in Japan.

PMID- 25986156
TI  - Letter Regarding 2014 Journal of Epidemiology Article by Nazrul Islam Mondal and
      Mahendran Shitan.

PMID- 25986155
TI  - Hearing Loss is Associated With Risk of Alzheimer's Disease: A Case-Control Study
      in Older People.
AB  - BACKGROUND: It remains unknown whether hearing loss increases the risk of
      Alzheimer's disease. This study aimed to examine the association between hearing
      loss and risk of Alzheimer's disease in older people in Taiwan. METHODS:
      Analyzing the database from Taiwan's National Health Insurance Program, this case
      control study enrolled 488 subjects >=65 years old with newly diagnosed
      Alzheimer's disease as a case group and 1952 subjects without Alzheimer's disease
      as a control group from 1998-2011. Patients with Alzheimer's disease and other
      comorbidities were identified by analyzing ICD-9 coding in claims data. The
      association of hearing loss, other comorbidities, and risk of Alzheimer's disease
      were compared between groups. RESULTS: After controlling for confounders,
      multivariable logistic regression showed an adjusted odds ratio of Alzheimer's
      disease of 1.39 in people with hearing loss (95% CI, 1.05-1.84) versus those
      without. Parkinson's disease (OR 4.44; 95% CI, 2.54-7.78), head injury (OR 2.31;
      95% CI, 1.46-3.66), depression (OR 1.68; 95% CI, 1.19-2.39), hypertension (OR
      1.40; 95% CI, 1.10-1.79), and age (each year, OR 1.03; 95% CI, 1.01-1.05) also
      showed strong links with Alzheimer's. CONCLUSIONS: Hearing loss is associated
      with increased risk of Alzheimer's disease in older people in Taiwan.

PMID- 25986157
TI  - Author's Response: Regarding the Relative Importance of Demographic,
      Socioeconomic and Health Factors on Life Expectancy in Low- and Lower-Middle
      Income Countries.

PMID- 25986160
TI  - Plastron-Mediated Growth of Captive Bubbles on Superhydrophobic Surfaces.
AB  - Captive bubbles on a superhydrophobic (SH) surface have been shown to increase in
      volume via injection of air through the surrounding plastron. The experimental
      contact diameter against volume trends were found to follow that predicted by the
      Surface Evolver simulation generally but corresponded with the simulated data at
      contact angle (CA) = 158 degrees  when the volume was 20 MUL but that at CA = 170
      degrees  when the volume was increased to 180 MUL. In this regime, there was a
      simultaneous outward movement of the contact line as well as a small reduction in
      the slope that the liquid-air interface makes with the horizontal as air was
      injected. At volumes higher than 180 MUL, air injection caused the diameter to
      reduce progressively until detachment. The inward movement of the contact line in
      this regime allowed the bubble body to undergo shape deformations to stay
      attached onto the substrate with larger volumes (300 MUL) than predicted (220 MUL
      at CA = 170 degrees ) using simulation. In experiments to investigate the effect
      of translating the SH surface, movement of captive bubbles was possible with 280
      MUL volume but not with 80 MUL volume. This pointed to the possibility of
      transporting gas-phase samples on SH surfaces using larger captive bubble
      volumes. 

PMID- 25986158
TI  - Moderate physical training attenuates perinatal low-protein-induced spleen
      lymphocyte apoptosis in endotoxemic adult offspring rats.
AB  - PURPOSE: To evaluate the effects of a moderate physical training (T) on the blood
      and splenic lymphocytes subsets and the rate of apoptosis in adult offspring
      submitted to perinatal low-protein (LP) diet. METHODS: Male Wistar rats were
      divided according to their mother's diet: control (C, 17 % casein) and
      undernourished (LP, 8 % casein). At the 60th day, pups were submitted to moderate
      physical training (8 weeks, 5 days week(-1), 60 min day(-1), at 70 % of VO2max).
      After T period, pups received an injection of lipopolysaccharide (LPS). B, NK,
      and TCD3+ lymphocytes subsets were analyzed by flow cytometry. Spleen lymphocytes
      apoptosis was evaluated by DNA fragmentation, phosphatidylserine externalization
      (PSE), and mitochondrial transmembrane depolarization (MTD) using a flow
      cytometer. Plasma TNF-alpha concentrations were analyzed by ELISA. RESULTS: LP +
      LPS pups showed a higher percentage of blood B, CD4+, and NK and a reduction in
      TCD3+, CD8+ than C pups. The percentage of NK and CD3+ was restored in LP + T +
      LPS pups. In the spleen, T normalized the percentage of NK in LP + LPS pups. LP +
      LPS pups showed a higher percentage of cells with PSE and MTD than C + LPS pups
      that was attenuated by T. The concentration of TNF-alpha was higher in LP + LPS
      than C + LPS, but it was attenuated in LP + T + LPS pups. CONCLUSION: Moderate
      physical training was able to revert the effects of perinatal LP diet on
      circulation lymphocytes subsets and attenuated splenic lymphocytes apoptosis and
      plasma TNF-alpha concentrations.

PMID- 25986159
TI  - The effect of a cinnamon-, chromium- and magnesium-formulated honey on glycaemic
      control, weight loss and lipid parameters in type 2 diabetes: an open-label cross
      over randomised controlled trial.
AB  - PURPOSE: This randomised controlled trial assessed the acute and long-term
      effects of daily supplementation of kanuka honey, formulated with cinnamon,
      chromium and magnesium on glucose metabolism, weight and lipid parameters in
      individuals with type 2 diabetes. METHODS: Twelve individuals with type 2
      diabetes received 53.5 g of a formulated honey and a control (non-formulated)
      kanuka honey in a random order for 40 days, using cross-over design. Fasting
      glucose, insulin, HbA1c, lipids and anthropometric measures were measured at
      baseline and end of treatment. A meal tolerance test was performed at baseline to
      assess acute metabolic response. RESULTS: There was no statistically significant
      difference in acute glucose metabolism between treatment groups, as measured by
      the Matsuda index and AUC for glucose and insulin. After the 40-day intervention
      with honey, fasting glucose did not differ significantly between the two
      treatments (95 % CI -2.6 to 0.07). There was no statistically significant change
      in HbA1c or fasting insulin. There was a statistically significant reduction in
      total cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23), LDL cholesterol by 
      0.29 mmol/L (95 % CI -0.57 to -0.23) and weight by -2.2 kg (95 % CI -4.2 to 
      0.1). There was a trend towards increased HDL and reduced systolic blood pressure
      in the intervention treatment. CONCLUSION: The addition of cinnamon, chromium and
      magnesium supplementation to kanuka honey was not associated with a significant
      improvement in glucose metabolism or glycaemic control in individuals with type 2
      diabetes. Use of the formulated honey was associated with a reduction in weight
      and improvements in lipid parameters, and should be investigated further.

PMID- 25986161
TI  - The utility of diffusion-weighted magnetic resonance imaging in differentiation
      of endometriomas from hemorrhagic ovarian cysts.
AB  - The aim was to determine the utility of diffusion-weighted magnetic resonance
      imaging (DW MRI) and apparent diffusion coefficient (ADC) measurements in
      differentiation of endometrioma and hemorrhagic ovarian cyst. A total of 24
      female patients who underwent pelvic MRI with an initial diagnosis of ovarian
      cyst were included in the study. The final diagnosis was endometrioma in 12
      patients and hemorrhagic ovarian cyst in 12 patients. We observed significantly
      lower ADC values in endometriomas compared with hemorrhagic ovarian cysts in all
      b values. DW MRI with quantitative ADC measurements can be used for
      differentiation of endometrioma from hemorrhagic ovarian cysts. 

PMID- 25986162
TI  - Choledochal cyst rupture with an intrahepatic pseudocyst mimicking hepatic
      mesenchymal hamartoma in an infant.
AB  - Spontaneous choledochal cyst rupture and consequent biliary peritonitis are rare
      in children. Here, we report a unique case of intrahepatic bile duct rupture of
      choledochal cyst type IV that resulted in loculated biliary peritonitis with an
      intrahepatic pseudocyst mimicking a hepatic mesenchymal hamartoma in a 3-month
      old boy. Magnetic resonance cholangiopancreatography can help differentiate these
      conditions. Regardless of the location, pseudocysts resulting from biliary
      peritonitis should be considered in cases of choledochal cysts with adjacent
      fluid collection or cystic lesions. 

PMID- 25986163
TI  - Fitz-Hugh-Curtis syndrome in a male patient due to urinary tract infection.
AB  - Fitz-Hugh-Curtis syndrome (FHCS) is inflammation of the liver capsule usually
      associated with pelvic inflammatory disease. FHCS has been rarely reported in
      male patients, and hematogenous and lymphatic spread to the liver is thought to
      be the underlying mechanism. Although a confirmatory diagnosis was made by
      laparoscopy, contrast-enhanced computed tomography scan is considered the first
      line imaging tool in clinical diagnosis of FHCS. We report a case of FHCS that
      developed in a young male patient with a urinary tract infection. 

PMID- 25986164
TI  - Preventing tuberculosis transmission at a maternity hospital by targeted
      screening radiography of migrants.
AB  - BACKGROUND: Israel has been the destination of large numbers of illegal migrants
      from East African countries in recent years. Despite efforts to detect and treat
      active tuberculosis (TB) at the border, 75% of all active TB cases diagnosed in
      our hospital were illegal migrants. In 2012, there was a large-scale TB exposure
      in our maternity ward, neonatal, and paediatric intensive care units following
      the admission of an infectious but apparently asymptomatic migrant who was in
      labour. A hospital-wide screening programme was subsequently implemented to
      prevent exposure of patients and staff to TB. AIM: To report the results of the
      first year of this intervention in the maternity hospital. METHODS: All illegal
      migrants from countries where TB is highly prevalent were screened by chest
      radiography (CR) upon admission to the maternity hospital. The results were
      immediately categorized by a radiologist as either 'suggestive of active
      pulmonary TB' or 'non-suggestive'. Patients with CR suggestive of TB were placed
      in airborne isolation and underwent further evaluation. FINDINGS: Four hundred
      and thirty-one apparently asymptomatic migrant women underwent CR screening. Most
      (363, 84%) presented in labour. Eleven women (2.6%) had a CR suggestive of active
      pulmonary TB which was confirmed in three (0.7% of screened women). No TB cases
      were missed by the CRs. Neither patients nor hospital staff were exposed to TB.
      CONCLUSION: Targeted CR screening for TB among high-risk women upon their
      admission to a maternity hospital had a high yield and was an effective strategy
      to prevent in-hospital transmission of TB.

PMID- 25986165
TI  - French recommendations for the prevention of 'emerging extensively drug-resistant
      bacteria' (eXDR) cross-transmission.
AB  - Controlling the spread of multi- or extensively drug-resistant bacteria (MDR or
      XDR) includes a dual strategy for reducing antibiotic prescriptions and
      preventing their spread from patient carriers. Standard precautions are
      applicable to all health professionals caring for any patients; additional
      barrier precautions (isolation) are recommended for patients carrying
      transmissible infectious diseases or MDR bacteria in sporadic or epidemic
      situations. Moreover, additional precautions may be required for populations at
      particular risk of infection or colonization by emerging XDR (eXDR), defined in
      our country as carbapenemase-producing Enterobacteriaceae and vancomycin
      resistant enterococci. Our ability to detect and identify eXDR carriers early and
      ensure their follow-up, through effective communication between all those
      involved, is a significant challenge for controlling their spread. Thus, the
      French High Committee for Public Health has updated and standardized all French
      existing recommendations concerning the prevention of the cross-transmission of
      these bacteria, and these recommendations are summarized in this review. The
      recommendations are based on scientific and operational knowledge up to 2013.
      Different preventive strategies are recommended for patients found to be carrying
      eXDR and those who are considered to be at risk of having eXDR because of a
      history of contact. The local context, the experience of the infection control
      team, the different times at which detection of eXDR takes place (during
      admission, hospitalization, etc.) and the epidemiological situation (sporadic
      cases, clusters, outbreaks, widespread epidemic) must be included in risk
      assessments that in turn inform the control measures that should be applied in
      each clinical circumstance. 

PMID- 25986166
TI  - Survival of vancomycin-intermediate Staphylococcus aureus on hospital surfaces.
AB  - BACKGROUND: Contaminated surfaces play an important role in the transmission of
      certain pathogens that are responsible for healthcare-associated infections.
      Although previous studies have shown that meticillin-resistant Staphylococcus
      aureus (MRSA) can survive on dry surfaces at room temperature, no published data
      regarding vancomycin-intermediate S. aureus (VISA) are available to date. AIM: To
      compare the survival time on different types of surfaces, cell-surface
      hydrophobicity, adherence to abiotic surfaces and biofilm formation of meticillin
      susceptible S. aureus (MSSA), MRSA and VISA. METHODS: Survival of the S. aureus
      strains was tested on latex, cotton fabric, vinyl flooring and formica. Cell
      surface hydrophobicity was determined using the hydrocarbon interaction affinity
      method. Adhesion to abiotic surfaces was tested on granite, latex (gloves),
      glass, vinyl flooring and formica. Biofilm formation was evaluated at 6, 12, 24
      and 48 h. FINDINGS: All of the samples survived on the vinyl flooring and formica
      for at least 40 days. VISA survived on both surfaces for more than 45 days. All
      of the strains were highly hydrophobic. VISA adhered to latex, vinyl flooring and
      formica. Biofilm formation increased for all of the tested strains within 6-24 h.
      CONCLUSION: VISA present high survival, adherence and cell-surface
      hydrophobicity. Therefore, as the treatment of patients with VISA is a
      significant challenge for clinicians, greater care with cleaning and disinfection
      of different types of surfaces in healthcare facilities is recommended because
      these may become important reservoirs of multi-resistant pathogens.

PMID- 25986167
TI  - Healthcare workers' decision-making about transmission-based infection control
      precautions is improved by a guidance summary card.
AB  - BACKGROUND: Transmission-based precautions (TBPs) are infection control measures
      designed to interrupt pathogen transmission. Success relies on early recognition
      of patients with potentially infectious syndromes, then the implementation of
      appropriate TBPs. We are aware of no literature evaluating interventions to
      facilitate healthcare workers (HCWs) in implementing TBPs. AIM: To evaluate the
      impact of a TBP guidance summary card on HCWs' decision-making about the
      appropriate implementation of TBPs. METHODS: A prospective audit was carried out
      to assess HCWs' ability to make decisions about TBP implementation. Following the
      first audit phase, staff were issued with a guidance card summarizing local TBP
      guidelines, identifying and addressing relevant TBP measures for infectious
      syndromes and specific organisms. The audit cycle was then completed to assess
      the impact of this intervention. FINDINGS: Baseline knowledge of appropriate TBP
      measures was low. Provision of a TBP summary card was significantly associated
      with the ability of staff carrying the card to correctly decide what TBPs are
      required in a variety of clinical situations, including Clostridium difficile
      infection [N = 107; odds ratio (OR): 27.0; 95% confidence interval (CI): 8.37
      86.8; P < 0.0001], norovirus diarrhoea and vomiting (N = 107; OR: 94.3, 95% CI:
      25.0-356; P < 0.0001), influenza-like illness (N = 107; OR: 85.2; 95% CI: 4.94
      1470; P < 0.0001) and the difference between surgical and FFP3 masks (N = 107;
      OR: 412; 95% CI: 23.4-7246; P < 0.0001). CONCLUSION: There is a lack of knowledge
      about TBP among HCWs. This study demonstrates how an inexpensive TBP summary card
      is an effective mechanism for improving (i) point-of-care access to TBP guidance
      and (ii) decision-making about appropriate implementation of TBP.

PMID- 25986168
TI  - STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in
      melanoma-bearing mice.
AB  - Therapeutic vaccines to induce anti-tumor CD8 T cells have been used in clinical
      trials for advanced melanoma patients, but the clinical response rate and overall
      survival time have not improved much. We believe that these dismal outcomes are
      caused by inadequate number of antigen-specific CD8 T cells generated by most
      vaccines. In contrast, huge CD8 T cell responses readily occur during acute viral
      infections. High levels of type-I interferon (IFN-I) are produced during these
      infections, and this cytokine not only exhibits anti-viral activity but also
      promotes CD8 T cell responses. The studies described here were performed to
      determine whether promoting the production of IFN-I could enhance the potency of
      a peptide vaccine. We report that cyclic diguanylate monophosphate (c-di-GMP),
      which activates the stimulator of interferon genes, potentiated the
      immunogenicity and anti-tumor effects of a peptide vaccine against mouse B16
      melanoma. The synergistic effects of c-di-GMP required co-administration of
      costimulatory anti-CD40 antibody, the adjuvant poly-IC, and were mediated in part
      by IFN-I. These findings demonstrate that peptides representing CD8 T cell
      epitopes can be effective inducers of large CD8 T cell responses in vaccination
      strategies that mimic acute viral infections.

PMID- 25986170
TI  - Exploring molecular fingerprints of selective PPARdelta agonists through
      comparative and validated chemometric techniques.
AB  - Peroxysome proliferator-activated receptors (PPARs) have grown greatly in
      importance due to their role in the metabolic profile. Among three subtypes
      (alpha, gamma and delta), we here consider the least investigated delta subtype
      to explore the molecular fingerprints of selective PPARdelta agonists. Validated
      QSAR models (regression based 2D-QSAR, HQSAR and KPLS) and molecular docking with
      dynamics analyses support the inference of classification-based Bayesian and
      recursive models. Chemometric studies indicate that the presence of ether
      linkages and heterocyclic rings has optimum influence in imparting selective
      bioactivity. Pharmacophore models and docking with molecular dynamics analyses
      postulate the occurrence of aromatic rings, HB acceptor and a hydrophobic region
      as crucial molecular fragments for development of PPARdelta modulators. Multi
      chemometric studies suggest the essential structural requirements of a molecule
      for imparting potent and selective PPARdelta modulation. 

PMID- 25986169
TI  - 3D tissue-like assemblies: A novel approach to investigate virus-cell
      interactions.
AB  - Virus-host cell interactions are most commonly analyzed in cells maintained in
      vitro as two-dimensional tissue cultures. However, these in vitro conditions vary
      quite drastically from the tissues that are commonly infected in vivo. Over the
      years, a number of systems have been developed that allow the establishment of
      three-dimensional (3D) tissue structures that have properties similar to their in
      vivo 3D counterparts. These 3D systems have numerous applications including drug
      testing, maintenance of large tissue explants, monitoring migration of human
      lymphocytes in tissues, analysis of human organ tissue development and
      investigation of virus-host interactions including viral latency. Here, we
      describe the establishment of tissue-like assemblies for human lung and neuronal
      tissue that we infected with a variety of viruses including the respiratory
      pathogens human parainfluenza virus type 3 (PIV3), respiratory syncytial virus
      (RSV) and SARS corona virus (SARS-CoV) as well as the human neurotropic
      herpesvirus, varicella-zoster virus (VZV). 

PMID- 25986171
TI  - A lazy learning-based QSAR classification study for screening potential histone
      deacetylase 8 (HDAC8) inhibitors.
AB  - Histone deacetylases 8 (HDAC8) is an enzyme repressing the transcription of
      various genes including tumour suppressor gene and has already become a target of
      human cancer treatment. In an effort to facilitate the discovery of HDAC8
      inhibitors, two quantitative structure-activity relationship (QSAR)
      classification models were developed using K nearest neighbours (KNN) and
      neighbourhood classifier (NEC). Molecular descriptors were calculated for the
      data set and database compounds using ADRIANA.Code of Molecular Networks.
      Principal components analysis (PCA) was used to select the descriptors. The
      developed models were validated by leave-one-out cross validation (LOO CV). The
      performances of the developed models were evaluated with an external test set.
      Highly predictive models were used for database virtual screening. Furthermore,
      hit compounds were subsequently subject to molecular docking. Five hits were
      obtained based on consensus scoring function and binding affinity as potential
      HDAC8 inhibitors. Finally, HDAC8 structures in complex with five hits were also
      subjected to 5 ns molecular dynamics (MD) simulations to evaluate the complex
      structure stability. To the best of our knowledge, the NEC classification model
      used in this study is the first application of NEC to virtual screening for drug
      discovery. 

PMID- 25986172
TI  - Expression vectors for C-terminal fusions with fluorescent proteins and epitope
      tags in Candida glabrata.
AB  - Candida glabrata is a haploid yeast considered the second most common of the
      Candida species found in nosocomial infections, accounting for approximately 18%
      of candidemias worldwide. Even though molecular biology methods are easily
      adapted to study this organism, there are not enough vectors that will allow
      probing the transcriptional and translational activity of any gene of interest in
      C. glabrata. In this work we have generated a set of expression vectors to
      systematically tag any gene of interest at the carboxy-terminus with three
      different fluorophores (CFP, YFP and mCherry) or three epitopes (HA, FLAG or
      cMyc) independently. This system offers the possibility to generate translational
      fusions in three versions: under the gene's own promoter integrated in its native
      locus in genome, on a replicative plasmid under its own promoter, or on a
      replicative plasmid under a strong promoter to overexpress the fusions. The
      expression of these translational fusions will allow determining the
      transcriptional and translational activity of the gene of interest as well as the
      intracellular localization of the protein. We have tested these expression
      vectors with two biosynthetic genes, HIS3 and TRP1. We detected fluorescence
      under the microscope and we were able to immunodetect the fusions using the three
      different versions of the system. These vectors permit coexpression of several
      different fusions simultaneously in the same cell, which will allow determining
      protein-protein and protein-DNA interactions. This set of vectors adds a new
      toolbox to study expression and protein interactions in the fungal pathogen C.
      glabrata. 

PMID- 25986173
TI  - Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping
      RAS-pathway activating mutations in borderline and cancerous neoplasms.
AB  - BACKGROUND: Mucinous ovarian tumors represent a distinct histotype of epithelial
      ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major
      histotypes, their genomic landscape remains poorly described. We undertook
      hotspot sequencing of 50 genes commonly mutated in human cancer across 69
      mucinous ovarian tumors. Our goals were to establish the overall frequency of
      cancer-hotspot mutations across a large cohort, especially those tumors
      previously thought to be "RAS-pathway alteration negative", using highly
      sensitive next-generation sequencing as well as further explore a small number of
      cases with apparent heterogeneity in RAS-pathway activating alterations. METHODS:
      Using the Ion Torrent PGM platform, we performed next generation sequencing
      analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2
      amplification status were sequenced independently for two mucinous carcinoma (MC)
      cases, previously established as showing ERBB2 amplification/overexpression
      heterogeneity, to assess the hypothesis of subclonal populations containing
      either KRAS mutation or ERBB2 amplification independently or simultaneously.
      RESULTS: We detected mutations in KRAS, TP53, CDKN2A, PIK3CA, PTEN, BRAF, FGFR2,
      STK11, CTNNB1, SRC, SMAD4, GNA11 and ERBB2. KRAS mutations remain the most
      frequently observed alteration among MC (64.9 %) and mucinous borderline tumors
      (MBOT) (92.3 %). TP53 mutation occurred more frequently in carcinomas than
      borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and
      mutation data suggest alterations occur in approximately 68 % of MC and as many
      as 20 % of MBOT. Proven and potential RAS-pathway activating changes were
      observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were
      observed in a substantial number of cases (7/63 total), as was co-occurrence of
      KRAS and BRAF mutations (one case). Microdissection of ERBB2-amplified regions of
      tumors harboring KRAS mutation suggests these alterations are occurring in the
      same cell populations, while consistency of KRAS allelic frequency in both ERBB2
      amplified and non-amplified regions suggests this mutation occurred in advance of
      the amplification event. CONCLUSIONS: Overall, the prevalence of RAS-alteration
      and striking co-occurrence of pathway "double-hits" supports a critical role for
      tumor progression in this ovarian malignancy. Given the spectrum of RAS
      activating mutations, it is clear that targeting this pathway may be a viable
      therapeutic option for patients with recurrent or advanced stage mucinous ovarian
      carcinoma, however caution should be exercised in selecting one or more
      personalized therapeutics given the frequency of non-redundant RAS-activating
      alterations.

PMID- 25986174
TI  - Characterization of efflux transport proteins of the human choroid plexus
      papilloma cell line HIBCPP, a functional in vitro model of the blood
      cerebrospinal fluid barrier.
AB  - PURPOSE: To characterize the human choroid plexus (CP) papilloma cell line HIBCPP
      with respect to ABC export protein expression and function in order to evaluate
      its use as an in vitro model to study carrier-mediated transport processes at the
      CP. METHODS: Expression profiles of ABC transporters were studied by quantitative
      real-time PCR and Western Blot analysis. Functionality of transporters was
      investigated by means of uptake experiments and permeation studies carried out on
      permeable filter systems. In addition, immunohistochemistry served to study
      localization of ABCC1 and ABCC4. RESULTS: Both qPCR and Western Blot revealed
      that ABC transporters known to be expressed in CP are also expressed in HIBCPP
      cells. Immunohistochemistry confirmed basolateral expression of ABCC1.
      Functionality of ABCC1, ABCC4, ABCB1 and ABCG2 could be shown in uptake assays.
      CONCLUSIONS: Altogether, the HIBCPP cells promise to be a functional and relevant
      in vitro tool to investigate transport processes at the blood-cerebrospinal fluid
      barrier.

PMID- 25986176
TI  - Brief report: vocational outcomes for young adults with autism spectrum disorders
      at six months after virtual reality job interview training.
AB  - Young adults with high-functioning autism spectrum disorder (ASD) have low
      employment rates and job interviewing presents a critical barrier to employment
      for them. Results from a prior randomized controlled efficacy trial suggested
      virtual reality job interview training (VR-JIT) improved interviewing skills
      among trainees with ASD, but not controls with ASD. We conducted a brief survey
      with 23 of 26 participants from this study to evaluate their vocational outcomes
      at 6-month follow-up with a focus on whether or not they attained a competitive
      position (employment or competitive volunteering). Logistic regression indicated
      VR-JIT trainees had greater odds of attaining a competitive position than
      controls (OR 7.82, p < 0.05). Initial evidence suggests VR-JIT is a promising
      intervention that enhances vocational outcomes among young adults with high
      functioning ASD. 

PMID- 25986175
TI  - Antibody-Drug Conjugates: Design, Formulation and Physicochemical Stability.
AB  - The convergence of advanced understanding of biology with chemistry has led to a
      resurgence in the development of antibody-drug conjugates (ADCs), especially with
      two recent product approvals. Design and development of ADCs requires the
      synergistic combination of the monoclonal antibody, the linker and the payload.
      Advances in antibody science has enabled identification and generation of high
      affinity, highly selective, humanized or human antibodies for a given target.
      Novel linker technologies have been synthesized and highly potent cytotoxic drug
      payloads have been created. As the first generation of ADCs utilizing lysine and
      cysteine chemistries moves through the clinic and into commercialization, second
      generation ADCs involving site specific conjugation technologies are being
      evaluated and tested. The latter aim to be better characterized and controlled,
      with wider therapeutic indices as well as improved pharmacokinetic
      pharmacodynamic (PK-PD) profiles. ADCs offer some interesting physicochemical
      properties, due to conjugation itself, and to the (often) hydrophobic payloads
      that must be considered during their CMC development. New analytical
      methodologies are required for the ADCs, supplementing those used for the
      antibody itself. Regulatory filings will be a combination of small molecule and
      biologics. The regulators have put forth some broad principles but this landscape
      is still evolving. 

PMID- 25986177
TI  - Timing of endoscopic third ventriculostomy in pediatric patients with congenital
      obstructive hydrocephalus: assessment of neurodevelopmental outcome and short
      term operative success rate.
AB  - The purpose of this study was to determine the impact of early (?6 months old),
      midterm (6-12 months old) and late (>12 months old) endoscopic third
      ventriculostomy (ETV) on the operative success rate and postoperative
      neurodevelopmental outcome of children with congenital obstructive hydrocephalus.
      We divided 63 children into three groups according to whether they underwent
      early, midterm or late ETV. Their preoperative developmental quotient (DQ) was
      assessed using the Gesell developmental diagnosis schedule (GDDS). Three and
      6months after the initial procedure, GDDS was used to obtain postoperative DQ
      from two assessments (blinded and non-blinded). Meanwhile, two observers studied
      the operative success rate of initial ETV. There were no substantial differences
      between blinded and non-blinded assessments. The success rate of early ETV was
      only 20.8%. By contrast, this rate was 55% and 73.7% for midterm and late ETV,
      respectively. Before operation, we observed severe developmental abnormalities in
      all children (DQ score<40). However, children in midterm and late ETV groups
      achieved improvement after the operation, which was particularly remarkable in
      late ETV group. Six months after the first surgery, 16 (84.2%) children in the
      late ETV group, nine (45%) in the midterm ETV group and four (16.7%) in the early
      ETV group had moderate developmental disability. Nevertheless, overall prognosis
      for the three groups was not optimistic. There were no children with mild
      neurodevelopmental disability or normal function. Our data confirmed that age is
      a determinant for ETV effectiveness and overall prognosis.

PMID- 25986179
TI  - Predictors of treatment failure following coil embolization of intracranial
      aneurysms.
AB  - We present a retrospective review of 357 consecutive patients with 419 aneurysms
      treated with coil embolization. Although incomplete occlusion and recurrence of
      intracranial aneurysms following coil embolization is a well-known problem, the
      factors that influence and predict treatment failure are still debated. For this
      study, we excluded non-coiling endovascular techniques (flow diversion) and non
      saccular aneurysms (fusiform). The modified Raymond-Roy occlusion classification
      (MRRC) was used to grade the aneurysms. Treatment failure was defined as filling
      of the aneurysm dome (MRRC Class IIIa or IIIb) at the first angiographic follow
      up (average 8 months). Univariate statistical tests were employed to select
      variables for incorporation into a multivariable logistic regression model.
      Multivariate analysis identified greater aneurysm volume (p<0.001), packing
      density (PD) less than 31% (p=0.007) and initial MRRC Class IIIb (p<0.001) as
      predictors of treatment failure. Incomplete neck coverage with coils was
      associated with treatment failure in univariate but not multivariate analysis.
      Class IIIb status was more predictive of treatment failure compared to all Class
      III (odds ratio 168 versus 14.4). Clinical outcomes were similar in both groups
      except that there were more retreatments in the treatment failure group
      (p<0.001). Aneurysm volume, PD and initial occlusion class are associated with
      angiographic outcome, consistent with prior literature. The MRRC is a powerful
      predictor of treatment failure. These results will be useful in the effort to
      both prevent and predict treatment failure after coil embolization, however, they
      should be verified in a prospective study.

PMID- 25986180
TI  - Cauda equina syndrome caused by retained hemostatic agents.
AB  - We report a patient with cauda equina syndrome secondary to retained Surgicel
      (Ethicon: Johnson & Johnson Medical, Piscataway, NJ, USA) and Gelfoam (Pfizer,
      New York, NY, USA). Retained hemostatic agents such as these used in spinal
      surgery can create space occupying lesions that lead to neurological compromise.
      There are few reports of neurologic symptoms caused by hemostatic devices used in
      surgery despite their widespread use. Our patient had routine lumbar
      microdiscectomy with preexisting motor deficits, and the acute postoperative
      course was complicated by a decline in neurologic function. The findings at the
      time of reoperation confirmed compression due to Gelfoam and Surgicel in the
      spinal canal, and subjective and objective symptoms partially improved after
      reoperation. 

PMID- 25986178
TI  - Transient monoplegia and paraesthesia after an epidural blood patch for a spinal
      cerebrospinal fluid leak.
AB  - We describe the very rare complication of new onset complete paralysis and
      numbness of one limb after an epidural blood patch in a 36-year-old woman.
      Intracranial hypotension resulting from a spinal cerebrospinal fluid fistula may
      be treated by epidural injection of autologous blood that is, a blood patch. This
      is usually a safe and effective procedure. The woman's muscle strength of hip
      flexion, extension, ankle dorsiflexion and plantarflexion decreased from 5/5 to
      0/5 following the procedure. After symptom onset, an MRI of her spine showed no
      compressive or ischaemic lesions amenable to urgent intervention. The cause of
      neurological deficit was at that time unknown and steroids were administered. Her
      symptoms persisted for about 2 days and gradually improved. In this paper, the
      management plan and the course of this rare and alarming complication is
      reported.

PMID- 25986181
TI  - Infiltrative lymphomatous optic neuropathy in non-Hodgkin lymphoma.
AB  - We report a 67-year-old man with non-Hodgkin lymphoma who presented with
      fluctuating visual loss which responded partially to steroid treatment. Multiple
      lumbar punctures did not show lymphoblastic cells and multiple MRI did not show
      any central nervous system disease except for isolated optic nerve enhancement. A
      fundus examination revealed combined arterial and venous occlusion and optic disc
      swelling. Due to conflicts between the examinations and investigations, there was
      a reluctance to initiate radiotherapy until progressive changes involving both
      eyes occurred. The man died 8 months after he was diagnosed with lymphoma. A post
      mortem optic nerve biopsy showed lymphomatous infiltration, confirming that the
      initial suspicion based on the clinical findings was correct.

PMID- 25986182
TI  - Retinal embolization after carotid endarterectomy and stenting for carotid artery
      stenosis.
AB  - To compare the incidence of retinal arterial embolism after carotid
      endarterectomy (CEA) or carotid artery stenting (CAS) as a treatment for carotid
      artery stenosis and to determine the risk factors for retinal artery
      embolization, this study included all consecutive severe carotid artery stenosis
      patients (70-99%), diagnosed by digital subtraction angiography, who underwent
      CEA or CAS between February 2014 and July 2014. The study included 61 patients in
      the CEA group and 71 patients in the CAS group. None of the patients developed a
      stroke or myocardial infarction or died within 7 days of the surgery. A total of
      15 patients exhibited retinal embolization including three patients who underwent
      CEA. None of these emboli caused symptoms. After undergoing CAS, 12 patients
      exhibited retinal embolization and one of the 12 patients suffered a decrease in
      visual acuity and visual field after CAS. The retinal embolization rate was 4.9%
      in the CEA group which was lower than the 16.9% rate in the CAS group (p=0.031).
      In addition, the retinal embolization rate in the ulcerated plaque group was
      higher than that in the non-ulcerated plaque group (p=0.007). Ulcerated plaques
      (odds ratio [OR] 5.043; 95% confidence interval [CI] 1.476-17.225; p=0.010) and
      CAS (OR 4.248; 95% CI 1.104-16.343; p=0.035) were independent predictors of
      retinal embolization. Although retinal embolization during CEA and CAS is common
      at our center, symptomatic embolization is not. The presence of ulcerated plaques
      and CAS were independent predictors of retinal embolization.

PMID- 25986183
TI  - Multimodality management of a giant skull base hemangioendothelioma of the
      sphenopetroclival region.
AB  - A 20-year-old man presented with proptosis, nasal obstruction, vision loss and
      cavernous sinus syndrome, ongoing for 6 years. Imaging and biopsy confirmed a
      middle skull base epithelioid hemangioendothelioma arising from the left
      sphenopetroclival region with infratemporal fossa and intracranial-intradural
      extension into the left temporal lobe. Preoperative embolization of the left
      internal maxillary artery followed by a combined neurosurgical (front-temporal
      orbito-zygomatic craniotomy) and otorhinolaryngology (maxillary swing) approach
      was performed for tumor debulking. Postoperative radiotherapy and maintenance
      interferon chemotherapy was given to achieve a favorable outcome at 6 months
      follow-up. We describe the pertinent clinical, genetic, radiological and
      histopathological features, along with the available therapeutic modalities for a
      primary giant skull base hemangioendothelioma.

PMID- 25986185
TI  - Use of emergency departments by known epileptic patients: An underestimated
      problem?
AB  - BACKGROUND AND PURPOSE: Seizure is a frequent reason of admission in emergency
      department (ED) but little is known about the proportion and the characteristics
      of known epileptic patients (KEPs) who used emergency services. METHODS: Over a
      12-month period, we prospectively recruited adults admitted for seizure to a
      tertiary hospital ED. For KEPs, clinical epilepsy features and characteristics of
      the admission were collected. RESULTS: Of the 60,578 ED admissions, 990 were
      related to seizure; 580 of these admissions concerned 448 different KEPs (257
      males; median age: 44); 339 were residents in the health district. Epilepsy was
      structural/metabolic in 268 (59.8%) patients, genetic in 44 (9.8%) and
      unknown/undetermined in 136 (30.3%); 218 (48.7%) patients were under a single
      antiepileptic drug and 135 (30.1%) were followed by an epileptologist. Of the 580
      KEP admissions, 440 (75.8%) concerned patients who had called the emergency
      medical assistance number, 252 (43.4%) with a discharge diagnosis of usual
      seizure and 43 (7.4%) of a status epilepticus. Half the KEPs were discharged
      without hospitalization. We estimated that 9.0% of KEPs residing in the district
      had used the ED during the period. CONCLUSION: Proportion of KEPs using ED is
      high. Most of the admissions concerned usual seizures suggesting that staff
      training and educational programmes for patients and for their relatives need to
      be improved. The organization of the prehospital and of the emergency medical
      services should also be adjusted to this specific need. Further research should
      be conducted to optimize the seizure care pathway for KEPs.

PMID- 25986187
TI  - Epilepsy services in Ireland: 'A survey of people with epilepsy in relation to
      satisfaction, preferences and information provision'.
AB  - BACKGROUND: A challenge facing modern health care systems is to develop and
      implement new models of service that deliver increased capacity while providing a
      higher-quality, more cost-effective service within resource constraints.
      Incorporating the experience of people with epilepsy must be seen as central to
      the effectiveness of service design and delivery. This paper, therefore, reports
      the views of people with epilepsy with regards to health service delivery in
      Ireland. METHOD: A cross-sectional descriptive survey design involving both
      quantitative and qualitative items was administered to a convenience sample of
      one hundred and two people with epilepsy (n=102) attending an epilepsy specialist
      centre. RESULTS: Despite high levels of satisfaction with hospital and primary
      care, participants offered several suggestions to improve healthcare delivery,
      such as: less delay in accessing specialist care and hospital appointments;
      better communication; and easier access to investigatory services. Findings
      demonstrate that for people with epilepsy the burden of the disorder is
      substantial and complex encompassing social, psychological and structural
      difficulties. Poor information provision particularly among women is reported.
      Furthermore, a lack of empowerment in people with epilepsy is highlighted.
      CONCLUSION: This study has implications for the reform and development of
      epilepsy services in relation to practice, education and research. It provides a
      basis for an evaluation of current practice and identifies opportunities for
      future service reorganization to improve the quality and efficiency of healthcare
      provision.

PMID- 25986186
TI  - A clinical variant in SCN1A inherited from a mosaic father cosegregates with a
      novel variant to cause Dravet syndrome in a consanguineous family.
AB  - A consanguineous family from Turkey having two children with intellectual
      disability exhibiting myoclonic, febrile and other generalized seizures was
      recruited to identify the genetic origin of these phenotypes. A combined approach
      of SNP genotyping and exome sequencing was employed both to screen genes
      associated with Dravet syndrome and to detect homozygous variants. Analysis of
      exome data was extended further to identify compound heterozygosity. Herein, we
      report identification of two paternally inherited genetic variants in SCN1A
      (rs121917918; p.R101Q and p.I1576T), one of which was previously implicated in
      Dravet syndrome. Interestingly, the previously reported clinical variant
      (rs121917918; p.R101Q) displayed mosaicism in the blood and saliva of the father.
      The study supported the genetic diagnosis of affected children as Dravet syndrome
      possibly due to the combined effect of one clinically associated (rs121917918;
      p.R101Q) and one novel (p.I1576T) variants in SCN1A gene. This finding is
      important given that heterozygous variants may be overlooked in standard exome
      scans of consanguineous families. Thus, we are presenting an interesting example,
      where the inheritance of the condition may be misinterpreted as recessive and
      identical by descent due to consanguinity and mosaicism in one of the parents. 

PMID- 25986188
TI  - Brivaracetam and carbamazepine interaction in healthy subjects and in vitro.
AB  - This phase I, open-label study investigated the effects of steady-state
      brivaracetam administration on steady-state pharmacokinetics of carbamazepine,
      and steady-state carbamazepine administration on single-dose and steady-state
      pharmacokinetics of brivaracetam, in 14 healthy participants who received
      brivaracetam 200mg single doses on days 1 and 22, and 200mg twice daily (bid) on
      days 24-35; and were titrated to carbamazepine 300mg bid on days 4-35.
      Brivaracetam did not significantly alter carbamazepine area under the plasma
      concentration-time curve (AUC) over a dosing interval, but resulted in a 2.6-fold
      increase in carbamazepine-epoxide. Carbamazepine decreased brivaracetam AUC by
      29%, while hydroxy-brivaracetam metabolite was increased by 17%. Urinary 6beta
      hydroxycortisol/cortisol ratio was unchanged by brivaracetam, but was increased 3
      fold by carbamazepine. In vitro hydrolysis of carbamazepine-epoxide in human
      hepatocytes was inhibited by brivaracetam, with an IC50 of 8.2MUM. Brivaracetam
      200mg bid was predicted to increase carbamazepine-epoxide by 2.3-fold, in close
      agreement with the observed value. In conclusion, brivaracetam did not modify
      carbamazepine exposure but increased carbamazepine-epoxide. Carbamazepine
      modestly decreased brivaracetam exposure and increased oxidative metabolism. 

PMID- 25986189
TI  - Treatment non-adherence as a trigger for status epilepticus: An observational,
      retrospective study based on therapeutic drug monitoring.
AB  - PURPOSE: To investigate the role of non-adherence to antiepileptic drug treatment
      as a trigger for status epilepticus (SE). METHODS: 124 consecutive admissions for
      SE in patients with established epilepsy were studied. Those who had had
      therapeutic drug monitoring at admission were identified. Non-adherence was
      defined as a serum concentration/dose ratio at admission of <75% of the patient's
      own trough control value. RESULTS: In 64 cases serum concentration/dose ratios at
      admission were available for comparison with morning trough values. Treatment non
      adherence was identified in a total of 24 (38%), 50% in children, 32% in patients
      16-59 years and in 44% above 60. Missed medication had been reported in only two
      of these patients. No cases with confirmed non-adherence had a fatal outcome
      (p=0.05). No significant differences between non-adherent and adherent admissions
      concerning demographic factors or epilepsy and SE characteristics were found.
      CONCLUSION: Antiepileptic drug non-adherence is a common cause of SE across all
      ages, but is not always identified due to the first history-based information
      often being elusive. Prompt and reliable recognition of non-adherence is
      imperative for correct management. This is the first study to demonstrate the
      extent of non-adherence by therapeutic drug monitoring in SE.

PMID- 25986190
TI  - Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate
      receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen syndrome.
AB  - OBJECTIVE: In Rasmussen syndrome (RS), in addition to the predominant involvement
      of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are
      also found, but their function has not been elucidated. We examined antibodies to
      N-methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B &
      GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients,
      and evaluated their changes over time and their roles in immunopathogenesis.
      METHODS: Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1
      were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months
      after the onset of RS. Epileptic patients without infectious etiology or
      progressive clinical course served as disease controls (n=23). Synthesized
      peptides encoding the extracellular and intracellular domains of human GluN2B and
      GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these
      antibodies as mean +2 standard deviations (optimal density) of the disease
      controls. MRI were evaluated according to the MRI staging proposed by Bien et al.
      (2002b, Neurology 58, 250). RESULTS: CSF levels of antibodies against N-terminal
      and C-terminal of GluN2B were higher in RS patients than in disease controls
      (p<0.01). Likewise, CSF levels of antibodies against N-terminal and C-terminal of
      GluN1 were also higher in RS patients than in disease controls (p<0.01). All four
      antibodies tested were below cut-off levels in almost all CSF samples collected
      within one year from epilepsy onset. The proportions of CSF samples with these
      antibodies above cut-off levels were highest from 12 to 23 months after epilepsy
      onset, and declined after 24 months. CSF levels of these antibodies were higher
      when seizure occurred daily than when seizure occurred less frequently (p<0.01),
      and were higher at MRI stage 3 than at MRI stages 0, 2 and 4 (p<0.05), except for
      anti-GluN1-CT antibody at stage 2. CONCLUSIONS: Broad epitope recognition
      spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS
      patients suggest that the autoantibodies are produced against NMDA type GluR
      antigens derived from cytotoxic T cell-mediated neuronal damages. These
      antibodies may impact the pathophysiology of RS in the most active stage, and
      could be a marker for active inflammation in the clinical course of RS. Further
      studies including passive transfer of the antibodies to mice may reveal the
      pivotal roles of the antibodies in RS.

PMID- 25986191
TI  - Antiepileptic drug use for treatment of epilepsy and dyslipidemia: Systematic
      review.
AB  - OBJECTIVE: To characterize the association between commonly used anti-epileptic
      drugs (AEDs) and plasma lipid levels in patients with epilepsy. METHODS: We
      sought observational studies that reported association between commonly used AEDs
      and plasma lipid levels in patients. The primary outcome was low-density
      lipoprotein (LDL) cholesterol. High-density lipoprotein (HDL), total cholesterol
      and triglyceride were secondary outcomes. The control group included healthy
      controls, pre-treatment patients or patients treated with other AEDs. We
      conducted a systematic search of major bibliographic databases and review of
      reference lists of primary articles and reviews. Primary comparisons of interest
      were: AED monotherapy vs. no AED use, monotherapy with one AED vs. other AED, and
      AED polytherapy vs. no AED use. RESULTS: 31 studies in 4126 people were
      identified. Carbamazepine, phenytoin and valproic acid were the most commonly
      studied drugs and were also implicated in causing considerable changes in plasma
      lipid levels in treated patients. There was an increase in LDL and total
      cholesterol levels with use of these three drugs; however, carbamazepine and
      phenytoin were also associated with higher levels of HDL. We could not identify
      one particular AED which was worse than the other in head-to-head comparison. We
      were unable to identify a particular polytherapy regimen that was worse than
      others. CONCLUSION: We found evidence to suggest that some AEDs may negatively
      alter lipids levels in patients with epilepsy. Both treating physicians and
      people with epilepsy need to be vigilant in managing their vascular risk factors
      to avoid vascular disease.

PMID- 25986192
TI  - Community-based epidemiological study of epilepsy in the Qena governorate in
      Upper Egypt, a door-to-door survey.
AB  - BACKGROUND: The aim of this study is to estimate the epidemiological features of
      epilepsy in a representative governorate of Upper Egypt. MATERIALS AND METHODS: A
      door-to-door community-based survey study was performed using a sample of 10
      areas among various districts of the Qena governorate in Upper Egypt. Six were
      classified as rural areas, and the remaining four were classified as urban areas,
      with a total population of 8027 inhabitants. The population was screened using an
      epilepsy-screening questionnaire. Positive cases with suspected epilepsy were
      referred to Qena University Hospital to be further evaluated by a qualified
      neurologist and for further investigations, such as neuroimaging and
      electroencephalography. RESULTS: One hundred patients had a confirmed diagnosis
      of epilepsy, with a lifetime prevalence of 12.46/1000. The active prevalence rate
      of epilepsy was 2.12/1000, while the incidence rate was 123/100000. Seventy-six
      percent of the patients had idiopathic epilepsies, while 24% had symptomatic
      epilepsy. Generalized epilepsies were more common (70.1%) than partial epilepsy
      (26.3%), meanwhile epilepsies with mixed seizure types were 2.6%. The most common
      seizure type was generalized tonic clonic seizures (51.8%). The age-specific
      prevalence rate of epilepsy was much higher in infancy and early childhood (62.5
      and 37.04/1000, respectively), which regressed steadily with age. Idiopathic
      epilepsies were significantly more common in urban areas than in rural areas
      (P=0.01), while symptomatic epilepsies were more common in rural areas than in
      urban areas (P<0.005). CONCLUSION: Upper Egypt is characterized by a relatively
      high incidence and prevalence of epilepsy and epilepsy-related medical service,
      and more cultural education should be directed to those areas in Egypt.

PMID- 25986194
TI  - Assessment of everyday memory functioning in temporal lobe epilepsy and healthy
      adults using the multifactorial memory questionnaire (MMQ).
AB  - Temporal lobe epilepsy (TLE) is associated with differing degrees of objective
      and subjective memory impairment. Memory self-report is an important part of the
      assessment process but few reliable and valid measures have been researched with
      this group. We thus aimed to explore subjective impairments with a robust
      measure: the multifactorial memory questionnaire (MMQ; Troyer and Rich, 2002).
      This was administered to 82 people with TLE and an age and education matched
      control group of the same size. The questionnaire probes worries about memory
      (MMQ-contentment); subjective forgetfulness (MMQ-ability); and use of
      compensatory strategies (MMQ-strategy). The TLE group reported significantly more
      worries about their memory, more instances of forgetfulness and use of more
      strategies than control participants. Strategy use was related to demographic
      factors in controls but not in the TLE group. Analysis of epilepsy related
      factors indicated that hemispheric laterlisation subgroups did not differ from
      one another on any subscale, nor did participants grouped according to their use
      of one, several, or no anti-epileptic medications. Measures of chronicity
      including age of onset and illness duration also failed to correlate with the MMQ
      subscales. Because objective memory performance is often impaired in more chronic
      and intractable cases, the lack of difference in subjective complaint is
      surprising and warrants future research to examine the relationship between this
      questionnaire and standardized test scores. We conclude that the MMQ is a
      clinical measure that could be used either outside or in tandem with
      neuropsychological assessment to gauge everyday memory difficulties among
      epilepsy patients. 

PMID- 25986193
TI  - Absence of Liver Toxicity in Perampanel-Treated Subjects: Pooled results from
      partial seizure phase III perampanel clinical studies.
AB  - OBJECTIVE: The liver plays a major role in the metabolism and elimination of many
      antiepileptic drugs (AEDs), including perampanel. Some of the metabolites
      identified for perampanel are likely formed via reactive intermediates, which
      have the potential to covalently bind to protein and cause idiosyncratic
      toxicities, including hepatotoxicity. The approved AED perampanel is a selective,
      noncompetitive AMPA receptor antagonist. The safety and tolerability of
      perampanel have been well documented in 3 double-blind, randomized, placebo
      controlled, phase III studies. Here we report the effects of perampanel on liver
      function in patients from the phase III studies to assess the potential for liver
      toxicity. METHODS: Following 6-week baseline, patients (>=12 years old) with drug
      resistant partial seizures were randomized to once-daily double-blind treatment
      (6-week titration, 13-week maintenance) with 2, 4, 8, or 12mg perampanel (n=1038)
      or with placebo (n=442). Clinical laboratory tests for hepatobiliary laboratory
      parameters were evaluated at baseline and at end of treatment. These included
      alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma
      glutamyl transpeptidase, and total bilirubin. Treatment-emergent markedly
      abnormal values (an increase in NCI-CTC grade relative to baseline and a grade
      >=2) and treatment-emergent adverse events (TEAEs) related to hepatobiliary
      parameters were also recorded. RESULTS: Mean hepatobiliary values were within
      normal ranges at baseline and end of treatment for all perampanel groups and
      placebo. Mean changes from baseline to end of treatment were small. The incidence
      of markedly abnormal results was very low for perampanel and placebo. TEAEs
      related to hepatobiliary parameters occurred in 0.4% of perampanel patients and
      0% of placebo patients. Hepatobiliary disorders included cholelithiasis (n=3 in
      perampanel) and abnormal hepatic function (n=1 in perampanel). None of the events
      were serious or led to perampanel discontinuation. No subject had values that met
      the criteria for Hy's Law. CONCLUSION: Hepatobiliary laboratory data and related
      TEAEs were not notably different between perampanel and placebo treatment groups,
      and no dose-related trends were observed. Based on the laboratory results from
      the 3 Phase III studies, perampanel (2, 4, 8, and 12mg) demonstrated no
      clinically important effects on liver function tests, indicating perampanel is an
      AED with a low potential for drug-induced liver toxicity.

PMID- 25986195
TI  - Long-term safety and efficacy of stiripentol for the treatment of Dravet
      syndrome: A multicenter, open-label study in Japan.
AB  - BACKGROUND: We have previously shown the benefits of short-term add-on
      stiripentol therapy for Dravet syndrome inadequately controlled by clobazam and
      valproate in Japanese patients. We report here the outcomes of long-term
      stiripentol use. METHODS: Patients with Dravet syndrome having >=4 clonic/tonic
      clonic seizures per 30 days while on clobazam and valproate (with or without
      bromide) received add-on stiripentol for 16 weeks. Those benefiting from
      stiripentol (50mg/kg/day; up to 2500mg/day) continued the therapy for additional
      up to 40 weeks. Responders were defined as those whose clonic/tonic-clonic
      seizures became <=50% frequent as compared to baseline. RESULTS: Of 24 patients
      starting stiripentol, 21 received the drug for >16 weeks and 19 completed the
      study. At the endpoint, the responder rate was 54%, with 2 patients remaining
      clonic/tonic-clonic seizure-free. Twenty-two patients experienced stiripentol
      related adverse events, with two having severe ones. They included somnolence
      (79%), loss of appetite (67%), ataxia (58%), and elevated gamma
      glutamyltransferase (38%). No adverse events led to study discontinuation, but 19
      patients required dose reduction for stiripentol and/or either antiepileptic drug
      combined. Stiripentol dose reduction was done in 9 patients, mostly due to
      somnolence or loss of appetite. CONCLUSIONS: During adjunctive stiripentol use
      with clobazam and valproate, careful monitoring for adverse events such as
      somnolence and loss of appetite is recommended, and dose reduction may become
      needed for any of the antiepileptics. Despite the need for safety precautions,
      the durable responses to stiripentol for up to 56 weeks suggest that the drug is
      effective as an adjunct to clobazam and valproate for the treatment of Dravet
      syndrome.

PMID- 25986196
TI  - Responders to vagus nerve stimulation (VNS) in refractory epilepsy have reduced
      interictal cortical synchronicity on scalp EEG.
AB  - EEG desynchronization has been proposed to be an important mechanism for
      antiepileptic effect of vagus nerve stimulation (VNS) but has never been clearly
      documented in human. The aim of this study was to evaluate impact of VNS on the
      synchronicity of interictal EEG rhythms. We estimated synchronization between
      scalp EEG signals using phase lag index (PLI) in 19 patients with chronic VNS
      therapy. We estimated changes in synchronization between ON and OFF phases and
      between responder (R) and non-responder (NR) patients. We found that R have a
      lower global level of synchronization (EEG broadband) than NR (p<0.0001) In
      addition, ON periods were characterized by lower values in comparison with OFF
      periods (p<0.001). R had significantly lower global synchronization levels in
      delta and alpha frequency bands (p<0.0001). Patients responding to VNS have thus
      a lower level of broadband EEG synchronization than non-responders. Estimating
      changes of synchronization level is thus a promising tool for predicting response
      to VNS. 

PMID- 25986197
TI  - Complete seizure freedom is possible in patients with MTLE-HS after surgery in
      spite of extratemporal electro-clinical features.
AB  - PURPOSE: The aim was to identify the common typical and atypical ictal semiologic
      and EEG features of patients with mesial temporal lobe epilepsy and hippocampal
      sclerosis who became seizure-free postoperatively. METHOD: The semiologic and EEG
      findings of 126 ictal video-EEG recordings of 50 patients who remained seizure
      free for at least 2 years (mean=9.46+/-3.20; range=3-14.5 years) after surgery
      were reviewed. Statistical analysis was used to determine the frequencies of the
      most common auras, semiologic features and EEG patterns and to define the symptom
      clusters. RESULTS: Aura was reported in 82% (n:41) of patients and the most
      common type was epigastric sensation. Early symptoms were contralateral upper
      extremity dystonic posturing (66%), oro-alimentary automatisms (50%) and
      ipsilateral hand automatisms (40%). Ictal EEG findings revealed localized and
      lateralized activity in 62% of patients. Of the 17 most common early symptoms,
      there was a tendency toward two clusters. Cluster 2 consisted of findings that
      were typical for patients with mesial temporal lobe epilepsy whereas Cluster 1
      mostly consisted of atypical findings. CONCLUSIONS: This study demonstrated two
      clusters of the semiologic repertoire, and the most frequent EEG finding was
      lateralized and localized ictal activity, while other types of EEG patterns were
      also recorded. Although the presence of atypical findings may suggest a more
      extended or even extratemporal zone, the seizure-free outcome demonstrated that
      if the critical amount of tissue can be resected within the epileptogenic
      network, this may be sufficient for termination of seizures.

PMID- 25986198
TI  - Functional brain connectome and sensorimotor networks in rolandic epilepsy.
AB  - PURPOSE: Rolandic epilepsy (RE) is a form of well-characterized childhood
      epilepsy whose focal electroencephalographic abnormalities affect the same well
      delineated local brain regions. Little is known about how the focal
      electroencephalographic discharges interfere with the topological organization of
      whole-brain networks in RE patients. METHODS: Seventy-three patients RE patients
      and 73 healthy children underwent rsfMRI. The whole-brain functional networks
      were constructed by thresholding the partial correlation matrices of 90 brain
      regions, and their topological properties were analyzed using graph theory-based
      approaches. We used network-based statistics to evaluate functional connectivity.
      The correlations between the network properties and the clinical and cognitive
      characteristics were calculated. RESULTS: The global topologic organization of
      the functional brain network was disrupted in RE patients, as manifested by
      reduced clustering coefficient and local and global efficiency and increased
      characteristic path length. The RE patients exhibited less connectivity among the
      sensorimotor areas; this reduction in the mean functional connectivity in this
      network correlated to altered global small-world properties. The RE patients
      exhibited decreased nodal centralities, predominantly in the bilateral
      postcentral gyrus, in the frontal, parietal and temporal lobes around the
      rolandic fissure and in areas related to linguistics and attention control
      (p<0.05, FDR-corrected). The altered nodal centralities in the bilateral
      postcentral gyrus and the left posterior cingulate cortex were correlated with
      subscales in Child Behavior Checklist. CONCLUSIONS: These results support the
      hypothesis that RE is associated with systemic brain disorganization and that the
      functional defect in rolandic areas contribute to symptomatology and
      electrophysiology in RE. Nodal abnormalities appear to imply the disturbances in
      linguistics and attention observed in RE patients.

PMID- 25986199
TI  - Ketogenic diet in patients with epileptic encephalopathy with electrical status
      epilepticus during slow sleep.
AB  - Epileptic encephalopathy with electrical status epilepticus during slow sleep
      (ESES) belongs to the group of epileptic encephalopathies that often prove
      refractory to AED treatment. The ketogenic diet (KD) has been used as an
      alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic
      encephalopathies. PURPOSE: In this retrospective study we assess the efficacy and
      tolerability of the KD in patients with ESES syndrome. METHODS: Between March 1,
      1990 and April 1, 2013, 65 patients who met diagnostic criteria of ESES syndrome
      were seen at our department. Twelve of them were placed on the KD and followed
      for a minimum of 18 months. RESULTS: The children had previously received a mean
      of 5.5 different AEDs and were on a mean of 3 AEDs when the diet was started.
      Eighteen months after initiating the diet, seven of the initial patients (58%)
      remained on the diet; one patient (8.3%) had become seizure free, one (8.3%) had
      a 75-99% decrease in seizures, two (16.6%) had a 50-74% decrease in seizures, and
      the remaining three children (24.9%) had a <50% decrease in seizures. In the
      patient who had become seizure free and in the one who had a 75-99% seizure
      decrease AEDs were reduced. CONCLUSION: The KD is a well-tolerated treatment
      option for patients with ESES syndrome, not only for structural cases but also
      for those with an unknown etiology. The diet should be considered in the
      management of this syndrome.

PMID- 25986200
TI  - Sleep influences the intracerebral EEG pattern of focal cortical dysplasia.
AB  - OBJECTIVE: Focal cortical dysplasia (FCD) is able to generate an intrinsic
      pathological EEG activity characterized by a continuous or near-continuous
      spiking. Different patterns of discharge were described. We examined
      quantitatively the distribution of the intracerebral FCD patterns in relation to
      sleep in order to investigate whether this activity is independent of
      thalamocortical influences. METHODS: We analyzed the first sleep cycle of 5
      patients with a diagnosis of FCD type II who underwent combined scalp
      intracranial electroencephalography (EEG), and showed an intracranial EEG pattern
      typical for FCD. Three patterns of FCD intracranial EEG activity were identified
      in all 5 patients, and visually marked for a maximum of 30min of each stage
      (wake, N1, N2, N3, REM): spike or polyspike exceeding 2Hz (pattern 1), spike or
      polyspike interrupted by flat periods below 2Hz (pattern 2) and discharges of
      >15Hz low-voltage rhythmic activity with regular morphology (pattern 3). After
      marking, the percentages of the three patterns across the different stages were
      calculated. RESULTS: The three patterns of FCD were present between 45% and 97%
      of the total time analyzed. Pattern 1 was the predominant pattern in wakefulness
      (73-100%), N1 (76-97%) and N2 (58-88.5%) in all patients, and in REM in 4 of 5
      patients (91-100%). During N2 and N3, there was an increase in pattern 2 in all
      patients, becoming the predominant pattern in 3 of the 5 patients during N3 (63
      89%). Pattern 3 was rare and only sporadically observed during N2 and N3.
      Wakefulness and REM sleep showed a similar pattern (pattern 1) with a slight
      amplitude reduction in REM sleep. SIGNIFICANCE: Despite the presence of an almost
      continuous discharge, sleep is an important modulator of the pathological EEG
      patterns found in FCD type II. This might suggest that dysplastic tissue is
      influenced by the thalamo-cortical control mechanisms involved in the generation
      of sleep.

PMID- 25986201
TI  - The incidence of unprovoked seizures and occurrence of neurodevelopmental
      comorbidities in children at the time of their first epileptic seizure and during
      the subsequent six months.
AB  - PURPOSE: To evaluate the incidence of unprovoked seizures in children and the
      prevalence of related neurodevelopmental comorbidities at the time of the
      presumed first seizure and six months thereafter. METHODS: The medical records of
      all children (0-18 years of age) seeking medical attention as the result of a
      first unprovoked seizure between September 1, 2001 and December 31, 2006, and
      registered in the population-based Stockholm Incidence Registry of Epilepsy
      (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the
      basis of the medical records from this first visit and from other healthcare
      during the following six months. RESULTS: The incidence of unprovoked seizures
      was between 30 and 204/100,000 person years (n=766) in the different age groups.
      It was highest among the youngest children and lowest among the 18-year-olds with
      small gender differences. The most common neurodevelopment comorbidities were
      developmental delay (22%, CI: 19-25%), speech/language and learning difficulties
      (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of
      neurodevelopmental comorbidity varied by age at the time of seizure onset, with
      cerebral palsy being more common among the 0-5-year-olds, attention deficits
      among the 6-16-year-olds, and autism and psychiatric diagnosis among the older
      children. An associated neurodevelopmental comorbidity was more common among
      those experiencing recurrent than single seizures during follow-up six months
      from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children
      there was no known or suspected neurodevelopmental comorbidity. CONCLUSION: The
      incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in
      the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were
      common already at the time of onset of the seizure disorder, indicating that
      neither seizure treatment nor seizures were the underlying cause of other
      neurodevelopmental symptoms in these patients during the period studied.

PMID- 25986202
TI  - Pneumomediastinum presenting as left periorbital subcutaneous emphysema.
AB  - Idiopathic spontaneous pneumomediastinum is rare but even rarer is associated
      unilateral periorbital subcutaneous emphysema. There is only 1 known case report
      noting both of these findings and was associated with endoscopic retrograde
      cholangiopancreatography complication. Isolated periorbital emphysema has been
      associated with dental procedures, facial trauma, and sneezing. It is has also
      been seen with pneumomediastinum caused by barotrauma, pneumothorax, endoscopic
      retrograde cholangiopancreatography, and esophageal perforation. A 52-year-old
      White male presents to the emergency department with complaint of left eye
      swelling that occurred overnight without known cause. He was found to have
      spontaneous idiopathic pneumomediastinum and unilateral periorbital subcutaneous
      emphysema. Although rare, it is important to rule out subcutaneous air tracking
      from pneumomediastinum when evaluating unilateral periorbital swelling in an
      otherwise asymptomatic patient.

PMID- 25986203
TI  - Significant Blood Loss in Lumbar Fusion Surgery for Degenerative Spine.
AB  - OBJECTIVE: Lumbar fusion is a widely used procedure for degenerative spine
      diseases but frequently is accompanied with substantial surgical blood loss. We
      aimed to investigate the risk factors for significant intraoperative blood loss
      and the influence of excessive bleeding on postoperative complications in
      patients undergoing fusion for degenerative lumbar spines. METHODS: For this
      retrospective study, we enrolled 199 patients who had undergone lumbar fusion
      surgery for degeneration. The definition of significant blood loss at operation
      was 500 mL or more in blood volume. The patients were subdivided into 2 groups on
      the basis of whether significant blood loss was present (n = 107) or not (n =
      92). RESULTS: The incidence of significant blood loss during lumbar fusion was
      53.8%. In the multivariate logistic regression model, the independent risk
      factors for significant blood loss included body mass index (P = 0.027), extreme
      spinal canal narrowing (P = 0.023), spine fusion segments >1 level (P = 0.008),
      and transforaminal lumbar interbody fusion (P = 0.006). Significant blood loss in
      lumbar fusion was associated with a greater incidence of postoperative
      complications (P = 0.002). The length of hospital stay for patents with excessive
      bleeding was prolonged significantly (P = 0.045). CONCLUSIONS: Because
      substantial bleeding in lumbar fusion is associated with a greater incidence of
      morbidities and prolonged length of hospital stay, attention to the risk factors
      for significant blood loss is important in the preoperative assessment and
      postoperative guidance for the level of care.

PMID- 25986204
TI  - Intraoperative Monitoring of Facial Nerve Motor-Evoked Potentials in Children.
AB  - OBJECTIVE: To determine whether transcranial motor-evoked potential monitoring of
      the facial nerve (FNMEP) during eloquent tumor resection is feasible in children
      and can predict both immediate and postoperative facial nerve (FN) function.
      METHODS: We included 24 consecutive procedures involving 21 patients (median age
      5.5 years, range 5 months to 15 years, 8 female) who were operated on with FNMEP
      monitoring by the first author in 2013 and 2014. During surgery, we maintained a
      constant response amplitude by increasing the stimulation intensity and aimed to
      establish a warning criterion based on the "threshold-level" method. A threshold
      increase of greater than 20 mA for eliciting the FNMEP in the most reliable
      facial nerve target muscle was considered to be a prediction of reduced
      postoperative facial nerve function and consequently, a warning was given to the
      surgeon. The preoperative and early postoperative function was documented with
      the House-Brackmann grading system. RESULTS: Monitoring of the FNMEP was feasible
      in all the surgeries in at least one facial nerve target muscle. The orbicularis
      oris muscle yielded the best result (95% of the trials), followed by the mentalis
      (87%) and orbicularis oculi muscles (86%). The median stimulation threshold was
      initially 65 mA (range 40-110 mA) for the FNMEP and 60 mA (15-220 mA) for the
      motor-evoked potential of the thenar muscles. The FNMEP deterioration showed a
      sensitivity of 100% for House-Brackmann deterioration and specificity of 74%.
      CONCLUSIONS: Intraoperative FNMEP monitoring is feasible and safe in infants and
      children. We found no evidence that the procedures and thresholds should differ
      from FNMEP monitoring in adults. FNMEP monitoring provides valid evidence for FN
      function in pediatric eloquent area surgery; its use is complementary to direct
      electrical FN stimulation and continuous EMG monitoring of FN target muscles.

PMID- 25986205
TI  - Unilateral Tailored Fronto-Orbital Approach for Giant Olfactory Groove
      Meningiomas: Technical Nuances.
AB  - OBJECTIVE: Giant olfactory groove meningiomas (maximum diameter >=6 cm) remain a
      surgical challenge. Historically, extensive anterior and antero-lateral
      approaches have been the primary approaches for removal of such large tumors with
      limitations and morbidity pertaining to each approach. Herein, the authors
      describe a minimally invasive, unilateral, tailored fronto-orbital approach for
      resection of these complex lesions with an emphasis on preservation of the
      anterior cerebral arteries and olfactory nerves. METHODS: A 4-stage approach
      using neuronavigation is performed: 1) predefined corridor, 2) identification of
      the ipsilateral anterior cerebral artery, 3) postdefined corridor, and 4) tumor
      base. The details of this approach are described below in a stepwise fashion and
      supplemented by a sample of 3 cases utilizing this technique. RESULTS: In the 3
      representative cases in which this technique was used, gross total resection was
      achieved without injury to any of the adjacent neurovascular structures.
      Significant sellar extension can be resected through a second stage endoscopic
      endonasal approach. CONCLUSION: Giant olfactory groove meningiomas (>=6 cm) can
      be safely and completely resected with this 4-stage, unilateral fronto-orbital
      technique. Furthermore, early identification and preservation of the adjacent
      critical neurovascular structures can be achieved. This technique avoids the
      inherent limitations and morbidity associated with the more classic pterional and
      bifrontal approaches respectively while minimizing normal tissue disruption.

PMID- 25986207
TI  - Plenty of motion at the bottom: atomically thin liquid gold membrane.
AB  - The discovery of graphene some ten years ago was the first proof of a free
      standing two-dimensional (2D) solid phase. Here, using quantum molecular dynamics
      simulations of nanoscale gold patches suspended in graphene pores, we predict the
      existence of an atomically thin, free-standing 2D liquid phase. The liquid phase,
      enabled by the exceptional planar stability of gold due to relativistic effects,
      demonstrates extreme fluxionality of metal nanostructures and opens possibilities
      for a variety of nanoscale phenomena. 

PMID- 25986206
TI  - Comparison of Maximal Lingual Pressure Generation During Isometric Gross and Fine
      Sensorimotor Tasks in Healthy Adults.
AB  - OBJECTIVES: To (1) compare 2 distinct isometric lingual press tasks, fine
      sensorimotor versus gross sensorimotor, at multiple sensor locations in relation
      to age and sex; and (2) provide a normative data set using a lingual
      strengthening device. DESIGN: Cohort study. SETTING: University. PARTICIPANTS:
      Healthy men and women (N=71; age range, 21-82y) recruited from the community.
      INTERVENTIONS: Participants were stratified by age and sex and divided into 3 age
      groups. Participants completed, in random order, 2 isometric tasks: (1) fine
      sensorimotor: tongue press maximally and discreetly against each of 5 sensors;
      and (2) gross sensorimotor: tongue press maximally against all 5 sensors
      simultaneously. MAIN OUTCOME MEASURES: Primary outcome was maximum isometric
      pressure in hectopascals (hPa). Secondary outcomes were time to reach peak
      pressure (s) and pressure gradient (hPa/s). RESULTS: Maximum pressures were
      significantly lower in those of older age for both fine and gross sensorimotor
      lingual tasks (P<.01), with the front and back sensors showing the greatest
      decline (35% and 45%, respectively). Pressure differences between tasks (P=.0012)
      resulted in the fine sensorimotor task generating higher pressures at the front
      sensor for all age groups. However, the gross sensorimotor task generated faster
      maximum pressures at all sensor locations for all age groups. For both
      sensorimotor tasks, subjects of older age as a whole generated less steep
      pressure gradients (P<.001). CONCLUSIONS: Age-related decline in tongue strength
      is greater at the anterior and posterior tongue. Results indicate a simpler gross
      sensorimotor task may be more beneficial for targeting timing as a biomechanical
      parameter during therapy, and the fine sensorimotor task may be more beneficial
      for targeting strength.

PMID- 25986208
TI  - Predictors for the need of surgery in antenatally detected hydronephrosis due to
      UPJ obstruction--a prospective multivariate analysis.
AB  - INTRODUCTION: Disagreement exists over the ability of different diagnostic tests
      to define obstruction, indications and timing of surgery and which patients will
      benefit from surgical intervention in antenatal hydronephrosis (ANH) due to
      ureteropelvic junction obstruction (UPJO). We try to find a way to predict which
      patients of ANH due to UPJO will eventually need surgery during conservative
      management. MATERIAL AND METHODS: Prospective single centre study involving 122
      renal units at a referral centre in India. Patients on conservative management
      were followed using a standard protocol and operated for pre-defined indications
      defining failure of conservative management. Patients who underwent surgery were
      compared with the non-operated group in terms of sex, side, baseline grade of
      hydronephrosis, maximum anterioposterior diameter on first postnatal ultrasound
      and differential renal function on first renal scan. RESULTS: A total of 109
      renal units qualified for conservative management. Of those, 23.9% required
      operative intervention during follow-up. Median time to failure of conservative
      management was 37 weeks. The median follow-up of non-operated cases was 54
      months. Univariate analysis revealed that society of fetal urology (SFU) grade of
      hydronephrosis, anteroposterior diameter (APD), cortical thickness (CT), and pre
      operative differential renal function (DRF) had a significant association with
      surgery (P < 0.05). Multivariate analysis revealed APD and pre-operative DRF as
      the only independent predictors for requiring surgery, while CT and initial SFU
      grade of hydronephrosis were not. Receiver operating curve analysis showed that
      an APD of 24.3 mm could predict the need for surgery, with a sensitivity of 73.1%
      and a specificity of 88.0%. CONCLUSIONS: APD and DRF are the predictive factors
      for surgery. We stop short of recommending surgery only on the basis of APD.
      Instead we recommend that efforts be made to improve the specificity of this
      criterion, or by using APD in perspective with the differential renal function.
      We can reduce the burden of investigations in those with APD <24 mm while those
      with APD >24 mm can be more comprehensively monitored.

PMID- 25986209
TI  - Sexual function in adult patients with classic bladder exstrophy: A multicenter
      study.
AB  - BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) comprises a spectrum
      of congenital anomalies that represents the severe end of urorectal
      malformations, and has a profound impact on continence as well as sexual and
      renal functions. OBJECTIVE: The relation between severity of BEEC and its
      associated functional impairments, on one hand, and the resulting restrictions in
      quality of life and potential psychopathology determine the patients' outcome. It
      is important for improving further outcome to identify BEEC-related sources of
      distress in the long term. Genital function and sexuality becomes an important
      issue for adolescent and adult BEEC individuals. Hence, the present study focused
      on sexual function and psychological adaption in patients with BEEC. STUDY
      DESIGN: In a multicenter study 52 patients (13 females, 39 males) with classic
      bladder exstrophy (BE) with their bladders in use were assessed by a self
      developed questionnaire about sexual function, and psychosexual and psychosocial
      outcome. The patients were born between 1948 and 1994 (median age 31 years).
      RESULTS: Twelve of 13 (92%) females and 25 of 39 (64%) males with classic BE had
      answered the questions on sexual function. Of these, 50% females and 92% males
      answered that they masturbated. Females had sexual intercourse more frequently.
      Six (50%) females affirmed dyspareunia whereas only two (8%) males reported pain
      during erection. Eight (67%) females specified having orgasms. Eighteen (72%)
      males were able to ejaculate. Two males and none of the females lived in a
      committed partnership (Figure). Two (15%) females and 13 (33%) males answered all
      psychosocial questions. The majority of these patients had concerns about
      satisfactory sexuality and lasting, happy partnerships. A minority of patients of
      both sexes were willing to answer psychosocial questions. Sexual activity and
      relationships of many adult BE patients seems to be impaired. Not surprisingly,
      sexual activity and awareness were different in males and females even in a multi
      organ anomaly. DISCUSSION: To date, one of the main goals of the medical
      treatment of BEEC/BE patients is to enable normal sexual life and fertility.
      However, only a few outcome studies have focused on these issues with
      contradicting results, most of them not using standardized outcome measures. In
      accordance with other studies, our female BE patients have dyspareunia and most
      of our male BE patients were able to ejaculate. But the question of normal force
      of ejaculation, ejaculated volume, or semen analysis remains unanswered. Despite
      partial confirmation of previous findings, there is inconsistency referring to
      the outcome measured by the available studies. This might in part be explained by
      the fact that, other than this study, most previous studies are the result of
      single-institution experience. Thus, selection bias in the patient sampling due
      to different a clinical collective in different hospitals may be the consequence.
      Furthermore, patients' honesty and self-reflection in answering difficult
      questions regarding their sexual and cosmetic impairments is questionable. In
      addition, studies include a wide range of age groups and are connected with this
      life period. Fears and condition-specific anxieties might change over time.
      Hence, the strengths of this study are the nationwide and treating physician
      independent data acquisition as well as the large sample size of adult patients
      with a very rare congenital malformation. Unfortunately, more detailed analyses
      on sexual function and current psychosocial situation, for example correlation of
      data with clinical symptoms such as continence status, was not possible as data
      were mainly not answered by patients. CONCLUSION: To improve the quality of life
      of patients with BEEC/BE, treatment and follow-up should emphasize physical but
      also psychological care in these patients. Physicians should further re-evaluate
      their preconceptions and should take care of the patients throughout their lives.

PMID- 25986210
TI  - Trauma systems are associated with increased level 3 trauma centers.
AB  - BACKGROUND: State-supported trauma systems have a proven association with
      improved mortality, but to date, there are no data reported on what mechanism
      leads to this benefit. Our hypothesis is that trauma systems with funding support
      are associated with increased number of trauma centers (TCs). MATERIALS AND
      METHODS: A retrospective population study: data for the number of American
      College of Surgeons-verified adult TCs in 2010 were obtained from the American
      College of Surgeons and for state-designated TCs from state departments of
      health. Population and gross domestic product (GDP) were obtained from the US
      Census. The main outcome measure was the number of TCs per population and per
      GDP. Statistical analysis was carried out using the Mann-Whitney U-test and
      Poisson regression. RESULTS: There was no association between a trauma system and
      the numbers of level 1 or 2 centers. In states with funded trauma systems, the
      numbers of level 3 centers per GDP and per million state population were 4.76 +/-
      2.37/$100 billion and 1.77 +/- 0.51/million people compared with 0.72 +/-
      1.72/$100 billion and 0.28 +/- 0.60/million people for unfunded states (P <
      0.05). Poisson multivariate regression identified system funding as an
      independent predictor of number of level 3 centers. CONCLUSIONS: Our study shows
      that the number of level 3 TCs significantly and independently correlated with
      the presence of a funded trauma system. The number of level 1 and 2 centers
      showed no such correlation. Further study will determine if increased number of
      level 3 centers leads to improved clinical outcome.

PMID- 25986211
TI  - Combining disparate surgical residencies into one: lessons learned.
AB  - BACKGROUND: Attitudes, career goals, and educational experiences of general
      surgery residents are profiled during the acquisition of a community residency
      program by an academic residency program. MATERIALS AND METHODS: The study
      population included all general surgery residents postgraduate years 2-5 in a
      tertiary academic medical center divided into community program matriculants
      (CPM) or academic program matriculants (APM). A survey compared perceptions
      before and after residency amalgamation in seven training categories as follows:
      relationships among residents, relationships with faculty, systems interactions,
      clinical training, surgical training, scholarship, and career plans. Responses
      were recorded on a Likert scale. Fisher exact test and one-sided t-test were
      applied. RESULTS: Thirty-five trainees (83%) participated, 23 APM (66%) and 12
      CPM (34%). Neither cohort reported significant negative perceptions regarding
      surgical training, career planning, or scholarship (P > 0.05). There was a
      greater likelihood of significant negative perceptions regarding inter-resident
      relationships among CPM (P < 0.05). CPM perceived significantly improved
      opportunities for scholarship (P < 0.01) and nationwide networking through
      faculty (P < 0.05) after acquisition. There was a nearly significant trend toward
      CPM perceiving greater access to competitive specialties after acquisition.
      Overall, CPM perceptions were affected more often after acquisition; however,
      when affected, APM were less likely to be positively affected (odds ratio, 2.9).
      CONCLUSIONS: Acquisition of a community surgery residency by an academic program
      does not seem to negatively affect trainees' perceptions regarding training. The
      effect of such acquisition on CPMs' decision to pursue competitive fellowships
      remains ill defined, but CPM perceived improved research opportunities, faculty
      networking, and programmatic support to pursue a career in academic surgery.

PMID- 25986212
TI  - Neighborhood socioeconomic status is associated with violent reinjury.
AB  - BACKGROUND: Measures of individual socioeconomic status correlate with recurrent
      violent injury; however, neighborhood socioeconomic status may also matter. We
      conducted a review of victims of interpersonal violence treated at our trauma
      center, hypothesizing that the percent of the population living under the poverty
      level in their neighborhood is associated with recurrent violent victimization.
      MATERIALS AND METHODS: We identified victims of interpersonal violence, ages 12
      24, in our trauma registry from 2005-2010. Recurrent episodes of violent injury
      were identified through 2012. The percentage of the population living under the
      poverty level for the patient's zip code of residence was derived from United
      States census estimates and divided into quartiles. Multivariable logistic
      regression was conducted to evaluate predictors of violent injury recidivism.
      RESULTS: Our cohort consisted of 1890 patients. Multivariable logistic regression
      confirmed the following factors as independent predictors of violent injury
      recidivism: male sex (odds ratio [OR] = 2 [1.06-3.80]; P = 0.03), black race (OR
      = 2.1 [1.44-3.06]; P < 0.001), injury due to firearms (OR = 1.67 [1.12-2.50]; P =
      0.01), and living in the lowest zip code socioeconomic quartile (OR = 1.59 [1.12
      2.25]; P = 0.01). CONCLUSIONS: For young patients injured by violence, the
      socioeconomic position of their neighborhood of residence is independently
      correlated with their risk of violent reinjury. Low neighborhood socioeconomic
      status may be associated with a disrupted sense of safety after injury and also
      may alter a person's likelihood of engaging in behaviors correlated with
      recurrent violent injury. Programs aimed at reducing violent injury recidivism
      should address needs at the individual and neighborhood level.

PMID- 25986213
TI  - The Value in Interprofessional, Collaborative-Ready Nutrition and Dietetics
      Practitioners.

PMID- 25986214
TI  - Video Consultations and Virtual Nutrition Care for Weight Management.

PMID- 25986215
TI  - Baroreflex activation in conscious rats modulates the joint inflammatory response
      via sympathetic function.
AB  - The baroreflex is a critical physiological mechanism controlling cardiovascular
      function by modulating both the sympathetic and parasympathetic activities. Here,
      we report that electrical activation of the baroreflex attenuates joint
      inflammation in experimental arthritis induced by the administration of zymosan
      into the femorotibial cavity. Baroreflex activation combined with lumbar
      sympathectomy, adrenalectomy, celiac subdiaphragmatic vagotomy or splenectomy
      dissected the mechanisms involved in the inflammatory modulation, highlighting
      the role played by sympathetic inhibition in the attenuation of joint
      inflammation. From the immunological standpoint, baroreflex activation attenuates
      neutrophil migration and the synovial levels of inflammatory cytokines including
      TNF, IL-1beta and IL-6, but does not affect the levels of the anti-inflammatory
      cytokine IL-10. The anti-inflammatory effects of the baroreflex system are not
      mediated by IL-10, the vagus nerve, adrenal glands or the spleen, but by the
      inhibition of the sympathetic drive to the knee. These results reveal a novel
      physiological neuronal network controlling peripheral local inflammation. 

PMID- 25986217
TI  - An optimized coupled assay for quantifying diaminopimelate decarboxylase
      activity.
AB  - Diaminopimelate decarboxylase (DAPDC) catalyzes the conversion of meso-DAP to
      lysine and carbon dioxide in the final step of the diaminopimelate (DAP) pathway
      in plants and bacteria. Given its absence in humans, DAPDC is a promising
      antibacterial target, particularly considering the rise in drug-resistant strains
      from pathogens such as Escherichia coli and Mycobacterium tuberculosis. Here, we
      report the optimization of a simple quantitative assay for measuring DAPDC
      catalytic activity using saccharopine dehydrogenase (SDH) as the coupling enzyme.
      Our results show that SDH has optimal activity at 37  degrees C, pH 8.0, and in
      Tris buffer. These conditions were subsequently employed to quantitate the enzyme
      kinetic properties of DAPDC from three bacterial species. We show that DAPDC from
      E. coli and M. tuberculosis have [Formula: see text] of 0.97 mM and 1.62 mM and a
      kcat of 55 s(-1) and 28 s(-1), respectively, which agree well with previous
      studies using more labor-intensive assays. We subsequently employed the optimized
      coupled assay to show for the first time that DAPDC from Bacillus anthracis
      possesses a [Formula: see text] of 0.68 mM and a kcat of 58 s(-1). This optimized
      coupled assay offers excellent scope to be employed in high throughput drug
      discovery screens targeting DAPDC from bacterial pathogens.

PMID- 25986216
TI  - A polymorphism in CCR1/CCR3 is associated with narcolepsy.
AB  - Etiology of narcolepsy-cataplexy involves multiple genetic and environmental
      factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype
      is strongly associated with narcolepsy, it is not sufficient for disease
      development. To identify additional, non-HLA susceptibility genes, we conducted a
      genome-wide association study (GWAS) using Japanese samples. An initial sample
      set comprising 409 cases and 1562 controls was used for the GWAS of 525,196
      single nucleotide polymorphisms (SNPs) located outside the HLA region. An
      independent sample set comprising 240 cases and 869 controls was then genotyped
      at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a
      SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077,
      P=1.6*10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated
      with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of
      candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and
      CCR3 mRNA levels were significantly lower in patients than in healthy controls,
      and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro
      chemotaxis assays were also performed to measure monocyte migration. We observed
      that monocytes from carriers of the rs3181077 risk allele had lower migration
      indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility
      genes for narcolepsy. These results highlight the potential role of CCR genes in
      narcolepsy and support the hypothesis that patients with narcolepsy have impaired
      immune function. 

PMID- 25986218
TI  - Infectious long non-coding RNAs.
AB  - Long non protein coding RNAs (lncRNAs) constitute a large category of the RNA
      world, able to regulate different biological processes. In this review we are
      focusing on infectious lncRNAs, their classification, pathogenesis and impact on
      the infected organisms. Here they are presented in two separate groups:
      'dependent lncRNAs' (comprising satellites RNA, Hepatitis D virus and lncRNAs of
      viral origin) which need a helper virus and 'independent lncRNAs' (viroids) that
      can self-replicate. Even though these lncRNA do not encode any protein, their
      structure and/or sequence comprise all the necessary information to drive
      specific interactions with host factors and regulate several cellular functions.
      These new data that have emerged during the last few years concerning lncRNAs
      modify the way we understand molecular biology's 'central dogma' and give new
      perspectives for applications and potential therapeutic strategies. 

PMID- 25986220
TI  - OmpA family proteins and Pmp-like autotransporter: new adhesins of Waddlia
      chondrophila.
AB  - Waddlia chondrophila is a obligate intracellular bacterium belonging to the
      Chlamydiales order, a clade that also includes the well-known classical Chlamydia
      responsible for a number of severe human and animal diseases. Waddlia is an
      emerging pathogen associated with adverse pregnancy outcomes in humans and
      abortion in ruminants. Adhesion to the host cell is an essential prerequisite for
      survival of every strict intracellular bacteria and, in classical Chlamydia, this
      step is partially mediated by polymorphic outer membrane proteins (Pmps), a
      family of highly diverse autotransporters that represent about 15% of the
      bacterial coding capacity. Waddlia chondrophila genome however only encodes one
      putative Pmp-like protein. Using a proteomic approach, we identified several
      bacterial proteins potentially implicated in the adhesion process and we
      characterized their expression during the replication cycle of the bacteria. In
      addition, we demonstrated that the Waddlia Pmp-like autotransporter as well as
      OmpA2 and OmpA3, two members of the extended Waddlia OmpA protein family, exhibit
      adhesive properties on epithelial cells. We hypothesize that the large diversity
      of the OmpA protein family is linked to the wide host range of these bacteria
      that are able to enter and multiply in various host cells ranging from protozoa
      to mammalian and fish cells. 

PMID- 25986221
TI  - Analysis of the complete Fischoederius elongatus (Paramphistomidae, Trematoda)
      mitochondrial genome.
AB  - BACKGROUND: Fischoederius elongates is an important trematode of Paramphistomes
      in ruminants. Animals infected with F. elongates often don't show obvious
      symptoms, so it is easy to be ignored. However it can cause severe economic
      losses to the breeding industry. Knowledge of the mitochondrial genome of F.
      elongates can be used for phylogenetic and epidemiological studies. FINDINGS: The
      complete mt genome sequence of F. elongates is 14,120 bp in length and contains
      12 protein-coding genes, 22 tRNA genes, two rRNA genes and two non-coding regions
      (LNR and SNR). The gene arrangement of F. elongates is the same as other
      trematodes, such as Fasciola hepatica and Paramphistomum cervi. Phylogenetic
      analyses using concatenated amino acid sequences of the 12 protein-coding genes
      by Maximum-likelihood and Neighbor-joining analysis method showed that F.
      elongates was closely related to P. cervi. CONCLUSION: The complete mt genome
      sequence of F. elongates should provide information for phylogenetic and
      epidemiological studies for F. elongates and the family Paramphistomidae.

PMID- 25986219
TI  - Characterization of Francisella tularensis Schu S4 defined mutants as live
      attenuated vaccine candidates.
AB  - Francisella tularensis (Ft), the etiological agent of tularemia and a Tier 1
      select agent, has been previously weaponized and remains a high priority for
      vaccine development. Ft tularensis (type A) and Ft holarctica (type B) cause most
      human disease. We selected six attenuating genes from the live vaccine strain
      (LVS; type B), F. novicida and other intracellular bacteria: FTT0507, FTT0584,
      FTT0742, FTT1019c (guaA), FTT1043 (mip) and FTT1317c (guaB) and created unmarked
      deletion mutants of each in the highly human virulent Ft strain Schu S4 (Type A)
      background. FTT0507, FTT0584, FTT0742 and FTT1043 Schu S4 mutants were not
      attenuated for virulence in vitro or in vivo. In contrast, Schu S4 gua mutants
      were unable to replicate in murine macrophages and were attenuated in vivo, with
      an i.n. LD50 > 10(5) CFU in C57BL/6 mice. However, the gua mutants failed to
      protect mice against lethal challenge with WT Schu S4, despite demonstrating
      partial protection in rabbits in a previous study. These results contrast with
      the highly protective capacity of LVS gua mutants against a lethal LVS challenge
      in mice, and underscore differences between these strains and the animal models
      in which they are evaluated, and therefore have important implications for
      vaccine development. 

PMID- 25986222
TI  - Effects of home-based exercise training on VO2 in breast cancer patients under
      adjuvant or neoadjuvant chemotherapy (SAPA): a randomized controlled trial.
AB  - BACKGROUND: Breast cancer chemotherapy is associated with a decline in measured
      cardiorespiratory fitness and increased fatigue. Physical activity has emerged as
      a feasible intervention to limit these side effects. Quantitative evaluation is
      necessary to propose a better-adapted physical activity and to evaluate efficacy.
      AIM: We undertook a prospective study to assess the effects of a home-based
      adapted physical activity (APA) program on aerobic capacity, strength, and
      fatigue in women treated with adjuvant or neoadjuvant chemotherapy for breast
      cancer versus usual care. DESIGN: This was an open two-arm, randomized controlled
      trial. SETTING: Study included outpatient groups in the Department of Physiology
      and Medical Oncology of a hospital in France. POPULATION: Forty-four patients
      treated with adjuvant or neoadjuvant chemotherapy for breast cancer. METHODS:
      Patients were randomly assigned to a control group or an APA group. Intervention
      consisted of a 3-week, home-based, supervised, combined APA program (endurance
      and resistance training) during 27 weeks. The primary endpoint was
      cardiopulmonary function assessed by maximal peak oxygen consumption (VO2peak).
      Secondary endpoints included a 6-minute Walking Test (6MWT), and assessment of
      muscular strength, fatigue, quality of life, physical activity level, and
      anxiety/depression. RESULTS: At 27 weeks, VO2peak increased by 1.83+/-0.68 ml.min
      1.kg-1 in the APA group (P=0.009) and decreased by 1.31+/-0.65 mL.min-1.kg-1 in
      the control group (P=0.046). The difference between the two groups was not
      significant (2.26+/-1.53 mL.min-1.kg-1, P=0.140) in intention-to-treat analysis,
      but it was significant in per protocol analysis (3.49+/-1.64 mL.min-1.kg-1,
      P=0.049). At 27 and 54 weeks, no significant differences were observed between
      the two groups for the cardiopulmonary exercise test, 6MWT, quadriceps strength,
      or quality of life. CONCLUSIONS: In breast cancer patients, a home-based
      supervised program during chemotherapy and radiotherapy treatment may be safe,
      feasible and increase VO2peak. In this study, heavy evaluation tests explain
      patient's non-adherence and do not permit to obtain statistically significant
      results between APA and control groups. CLINICAL REHABILITATION IMPACT: Aerobic
      home-based adapted physical activity is beneficial on aerobic capacity.

PMID- 25986223
TI  - Changes of gait parameters following long-term aerobic endurance exercise in
      mildly disabled multiple sclerosis patients: an exploratory study.
AB  - BACKGROUND: The long-term effects of walking based aerobic endurance exercise on
      gait parameters have not yet been sufficiently investigated in patients with
      multiple sclerosis (MS). AIM: To investigate the effects of an aerobic walking
      exercise program on gait parameters in MS patients over a period of 12 months.
      DESIGN: Non-randomized, controlled, exploratory trial. SETTING: Outpatient, home
      based program. POPULATION: Sixty ambulatory patients with relapsing-remitting MS
      and an EDSS<=3.5 participating in an individualized twelve month aerobic
      endurance exercise program were evaluated during a treadmill exercise by video
      recordings with regard to step cadence, step length and ground contact time at
      baseline and every three months thereafter for twelve months. RESULTS: From the
      44 patients who completed the study, the ground contact time of the feet was
      significantly elevated at two load steps (3.2 km/h with 3.5% slope and 4.8 km/h
      at 7.5% incline) after 12 months (P<0.001, np2=0.2; P=0.01, np2=0.1). The step
      cadence decreased significantly at 3.2 km/h speed with 3.5% slope (P<0.001,
      np2=0.2) and the step length increased significantly at the same load step
      (P<0.001, np2=0.15). Post-hoc analysis revealed no changes in any of the analyzed
      gait parameters in the internal control group (N.=16) who performed a treadmill
      exercise after 12 months. CONCLUSION: Walking based aerobic endurance exercise
      may contribute to improved gait parameters in MS patients. Further prospective
      controlled studies are needed to investigate the impact of long-term endurance
      walking exercise on gait parameters and stability in MS patients. CLINICAL
      REHABILITATION IMPACT: The observation that mere walking-based exercise changes
      gait parameters and could therefore possibly contribute to gait stability without
      specific balance or muscular training might largely facilitate treatment
      recommendations for mildly disabled MS patients.

PMID- 25986224
TI  - Psychometric properties of the Duke Health Profile in a neuromuscular disease
      population.
AB  - BACKGROUND: Quality of life is a subjective point of view of the patient. Its
      measurement is complex, but useful to personalize interventions and to evaluate
      the effect of care, particularly in physical medicine. AIM: To determine the
      psychometric properties of the Duke Health Profile (DHP) in neuromuscular
      disease. This instrument was chosen for its excellent acceptability and its
      ability to evaluate ten dimensions in a short administration. DESIGN: Prospective
      multicentre study. SETTING: Neuromuscular patients in centers in Reims, Dijon and
      Besancon. POPULATION: Patients over 18 years with neuromuscular disorders.
      METHODS: Successive inclusion between 2002 and 2005; DHP administration on two
      occasions, 15 days apart; collection of socio-demographic data. Statistical
      analyses using SAS SOFTWARE 9.3. RESULTS: One hundred thirty-nine patients were
      included. The acceptability of the DHP was excellent. The disability dimension
      showed marked ceiling effect. Reliability was acceptable (Cronbach=0.54-0.73,
      except for the social health dimension [0.40], ICC=0.55-0.83). The anxiety and
      depression dimensions had discriminant properties in distinguishing patients with
      different functional status. CONCLUSION: The DHP is suitable and valid for
      patients with neuromuscular disease, with some reservations for the social health
      and disability dimensions. CLINICAL REHABILITATION IMPACT: This tool can be used
      in daily clinical practice and in research.

PMID- 25986225
TI  - Contributing to the growth of Physical and Rehabilitation Medicine (PRM): call
      for a Cochrane Field in PRM.
AB  - The European Society of Physical and Rehabilitation Medicine (ESPRM), together
      with the European Journal of PRM and the PRM Section and Board of the European
      Union of Medical Specialists (UEMS), started an action to establish a
      relationship with Cochrane (formerly the Cochrane Collaboration). Cochrane is a
      global, independent network of researchers, professionals, patients, carers and
      people interested in health, with contributors from more than 130 countries. Its
      aim is to produce credible, accessible health information that is free from any
      conflicts of interest. Cochrane produces the Cochrane Library, an evidence-based
      resource that includes today more than 6300 Cochrane systematic reviews. Cochrane
      is made up of many different review groups and other entities (such as Centres
      and Branches), distributed around the world, that are mainly focused on specific
      healthcare problems (diseases, or organs). Inside Cochrane also Fields have been
      created, that focus on a dimension of health care other than a specific
      healthcare problem. A Cochrane Field represents a bridge between Cochrane and the
      stakeholders of the related healthcare area. The medical specialty of PRM is
      covering a broad medical domain: it deals with function, activities and
      participation in a large number of health conditions, mostly but not exclusively
      musculoskeletal, neurological and cardiorespiratory. Consequently, the currently
      more than 200 existing Cochrane Reviews are scattered among different groups. A
      PRM Field could greatly serve to the need of the specialty, spreading the actual
      Cochrane knowledge, focusing needs today not covered by Cochrane Reviews, facing
      the intrinsic methodological problems of the specialty. This paper introduces a
      call for the development of a PRM Cochrane Field, briefly reviewing what Cochrane
      is and how it is organized, defining the value and identifying a pathway toward
      the development of a PRM Cochrane Field, and finally shortly reviewing the
      Cochrane reviews of PRM interest. 

PMID- 25986227
TI  - Signal Processing for Wireless Communication MIMO System with Nano- Scaled CSDG
      MOSFET based DP4T RF Switch.
AB  - In the present technological expansion, the radio frequency integrated circuits
      in the wireless communication technologies became useful because of the
      replacement of increasing number of functions, traditional hardware components by
      modern digital signal processing. The carrier frequencies used for communication
      systems, now a day, shifted toward the microwave regime. The signal processing
      for the multiple inputs multiple output wireless communication system using the
      Metal- Oxide-Semiconductor Field-Effect-Transistor (MOSFET) has been done a lot.
      In this research the signal processing with help of nano-scaled Cylindrical
      Surrounding Double Gate (CSDG) MOSFET by means of Double- Pole Four-Throw Radio
      Frequency (DP4T RF) switch, in terms of Insertion loss, Isolation, Reverse
      isolation and Inter modulation have been analyzed. In addition to this a channel
      model has been presented. Here, we also discussed some patents relevant to the
      topic.

PMID- 25986228
TI  - Recent developments in testing techniques for elastic mechanical properties of 1
      D nanomaterials.
AB  - One-dimensional (1-D) nanomaterials exhibit great potentials in their
      applications to functional materials, nano-devices and systems owing to their
      excellent properties. In the past decade, considerable studies have been done,
      with new patents being developed, on these 1-D building blocks for for their
      mechanical properties, especially elastic properties, which provide a solid
      foundation for the design of nanoelectromechanical systems (NEMS) and predictions
      of reliability and longevity for their devices. This paper reviews some of the
      recent investigations on techniques as well as patents available for the
      quantitative characterization of the elastic behaviors of various 1-D
      nanomaterials, with particular focus on on-chip testing system. The review begins
      with an overview of major testing methods for 1-D nanostructures' elastic
      properties, including nanoindentation testing, AFM (atomic force microscopy)
      testing, in situ SEM (scanning electron microscopy) testing, in situ TEM
      (transmission electron microscopy) testing and the testing system on the basis of
      MEMS (micro-electro-mechanical systems) technology, followed by advantages and
      challenges of each testing approach. This review also focuses on the MEMS-based
      testing apparatus, which can be actuated and measured inside SEM and TEM with
      ease, allowing users to highly magnify the continuous images of the specimen
      while measuring load electronically and independently. The combination of on-chip
      technologies and the in situ electron microscopy is expected to be a potential
      testing technique for nanomechanics. Finally, details are presented on the key
      challenges and possible solutions in the implementation of the testing techniques
      referred above. 

PMID- 25986226
TI  - Mitral valve analysis adding a virtual semi-transparent annulus plane for
      detection of prolapsing segments.
AB  - BACKGROUND: We hypothesized that a novel three-dimensional virtual semi
      transparent annulus plane (3D VSAP) presented on a holographic screen can be used
      to visualize the prolapsing tissue in degenerative mitral valve disease and
      furthermore, provide us with geometrical data of the mitral valve apparatus.
      Phantom and patient studies were designed to demonstrate the feasibility of
      creating a semi-automatic, semi-transparent mitral annulus plane visualized on a
      holographic display. METHODS: Ten pipe cleaners mimicking the mitral annulus with
      different shapes and three types of annuloplasty rings served as phantoms. We
      obtained 3D transoesophageal examination of the phantoms in a special designed
      box filled with water. Recordings were converted to the holographic display and a
      3D VSAP was created. The ratio of the major and minor axes as well as the non
      planar angles were calculated and compared with direct measures of the phantoms.
      Forty patients with degenerative mitral valve disease were then analyzed with 3D
      transthoracic echocardiography (TTE) and a 3D VSAP was created on the holographic
      display. A total of 240 segments were analyzed by two independent observers, one
      echo expert (observer I), and the other novice with limited echo experience
      (observer II). The two observers created the 3D VSAP in each patient before
      suggesting the valve pathology. RESULTS: The major/minor axes ratio and non
      planar angles by 3D VSAP correlated with direct measurements by r = 0.65, p <
      0.02 and r = 0.99, p < 0.0001, respectively. The sensitivity and specificity of
      the 3D VSAP method in patients was 81 and 97%, respectively (observer I) and for
      observer II 77 and 96%, respectively. The accuracy and precisions were 93.9 and
      89.4%, respectively (observer I), 92.3 and 85.1% (observer II). Mitral valve
      analysis adding a 3D VSAP was feasible with high accuracy and precision,
      providing a quick and less subjective method for diagnosing mitral valve
      prolapse. This novel method may improve preoperative diagnostics and may relieve
      a better understanding of the pathophysiology of mitral valve disease. Thus,
      based on the specific findings in each patient, a tailored surgical repair can be
      planned and hopefully enhance long-term repair patency in the future.

PMID- 25986229
TI  - Gold nanoparticles enhancing protontherapy efficiency.
AB  - The insertion of gold nanoparticles in biological liquids, tissues and organs
      permits to increase the equivalent atomic number of the medium that, if used as
      target to be irradiated by ionizing radiation, permits an increment of the
      absorbed dose. No toxic nanoparticles, such as the Au, can be injected in the
      cancer tissues at different concentrations before using a localized treatment
      that uses energetic proton beams for radiotherapy. Due to the high density and
      atomic number of the used gold nanoparticles, the absorbed radiation dose can be
      increased to about a factor six per cent using relatively low concentration of
      nanoparticles injectable as solution in the tumor tissue. This means to reduce
      the exposition to ionizing radiation or to increase the dose to the tumor site.
      Simulation programs of proton energy loss in tissues, using SRIM Code, are
      employed to evaluate the Bragg peak enhancing in presence of Au nanoparticles, so
      it will be presented and discussed. Some research findings and patents in the
      gold nanoparticle preparation and application to Medicine are reviewed in the
      present paper. 

PMID- 25986230
TI  - A sound absorptive element comprising an acoustic resonance nanofibrous membrane.
AB  - As absorption of sound of lower frequencies is quite problematic with fibrous
      material made up of coarser fibers, development of highly efficient sound
      absorption material is called for. This is why this work deals with the
      development of new high sound absorption material. To absorb the low frequencies,
      especially the structures based on resonance principle of nanofibrous layers are
      used, when through resonance of some elements the acoustic energy is transferred
      into thermal energy. The goal of the invention is achieved by a sound absorbing
      means which contains resonance membrane formed by a layer of polymeric
      nanofibers, which is attached to a frame. For production of nanofibrous
      membranes, the cord electrospinning was used. The resonance membrane was then,
      upon impact of sound waves of low frequency, brought into forced vibrations,
      whereby the kinetic energy of the membrane was converted into thermal energy by
      friction of individual nanofibers, by the friction of the membrane with ambient
      air and possibly with other layers of material arranged in its proximity, and
      some of the energy was also transmitted to the frame, through which the
      vibrations of the resonance membrane were damped. The density and shape of the
      mesh of frame formations determine the resonance frequency of the acoustic means.
      The goal of the invention is therefore to eliminate or at least reduce the
      disadvantages of the present state of the art and to propose sound absorbing
      means that would be capable of absorbing, with good results sounds in as broadest
      frequency range as possible. Here, we also discussed some patents relevant to the
      topic.

PMID- 25986231
TI  - Commentary on article by Ferguson et al.: "A comparison of lateral release rates
      in fixed- versus mobile-bearing total knee arthroplasty".

PMID- 25986232
TI  - Mantle cell lymphoma first presenting as immune complex-mediated
      glomerulonephritis: a case report.
AB  - INTRODUCTION: Kidney involvement in non-Hodgkin lymphoma is recognized but mostly
      diagnosed following a diagnosis of lymphoma. We describe a rare case of mantle
      cell lymphoma, a B-cell-type non-Hodgkin lymphoma, first presenting with immune
      complex glomerulonephritis. CASE PRESENTATION: We report the case of a 58-year
      old Sri Lankan man who presented with gross hematuria. Further investigation
      revealed bicytopenia with splenomegaly and elevated serum creatinine. He had a
      renal biopsy, which revealed acute immune complex glomerulonephritis with
      interstitial inflammation. Results from an initial bone marrow biopsy and blood
      imaging were inconclusive. Three months later his renal function had deteriorated
      and a lymph node biopsy revealed mantle cell lymphoma. Within three months of
      initiating chemotherapy, his renal function returned to normal levels and
      remained normal at one year of follow-up. CONCLUSIONS: It is important to have a
      high degree of suspicion when patients present with acute immune complex
      glomerulonephritis with no other identifiable cause, because it could be the
      first presentation of a non-Hodgkin lymphoma such as mantle cell lymphoma.

PMID- 25986233
TI  - Managing women presenting with urinary incontinence: is hardiness significant?

PMID- 25986234
TI  - Comments on Lowenstein et al.: Incidence and lifetime risk of pelvic organ
      prolapse surgery in Denmark from 1977 to 2009.

PMID- 25986236
TI  - Ultrafast excited-state processes in inorganic systems.

PMID- 25986235
TI  - Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells
      and are correlated with the poor prognosis in colorectal cancer.
AB  - BACKGROUND: Dying tumor cells after irradiation could promote the proliferation
      of living tumor cells might cause tumor relapse and treatment failure. Our
      previous study showed that activated caspase-3 after irradiation probably
      participates in tumor repopulation. In this study, we investigated whether high
      mobility group box 1(HMGB1) is also involved in tumor repopulation. METHODS:
      Colorectal tumor cells were irradiated. The cleaved caspase-3 (CC3) in irradiated
      tumor cells and HMGB1 in the supernatant of irradiated tumor cells were detected
      by Western blot. A large number of irradiated colorectal tumor cells (feeder
      cells) were then co-cultured with a small number of luciferase-labeled living
      colorectal tumor cells (reporter cells) and proliferation of reporter cells was
      measured by bioluminescence imaging. The CC3 and HMGB1 protein expression in
      colorectal tumor and peritumoral tissues were detected by immunohistochemistry
      and their correlation with prognosis were analyzed. RESULTS: The irradiated
      colorectal tumor cells underwent apoptosis and necrosis and produced CC3 in tumor
      cells and HMGB1 in the supernatant of cultured cells. The increased expression of
      secretory HMGB1 correlated with CC3 level and proliferating cell nuclear antigen
      (PCNA) after irradiation in vitro. The irradiated dying cells remarkably
      stimulated living tumor cell proliferation. Interestedly, immunohistochemistry
      staining showed that positive HMGB1, CC3, and Ki67 expression were significantly
      higher in colorectal tumor tissues than in peritumoral tissues (p <0.01). The
      Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels
      were significantly associated with poor prognosis (p <0.05, p <0.01).
      Multivariate analysis using Cox proportional hazards model showed that TNM
      staging and HMGB1 were independent prognostic factors in patients with colorectal
      cancer (CRC) (p <0.01, p <0.001). CONCLUSION: Both apoptotic and necrotic cells
      could stimulate proliferation of living tumor cells, and the increased expression
      of CC3 and HMGB1 in tumor cells could be new markers for poor prognosis in
      colorectal cancer patients.

PMID- 25986237
TI  - Aging-related renal injury and inflammation are associated with downregulation of
      Klotho and induction of RIG-I/NF-kappaB signaling pathway in senescence
      accelerated mice.
AB  - BACKGROUND AND AIMS: The predominant distribution of the antiaging Klotho protein
      in both the kidneys and brain may point to its essential role in protecting
      against dysfunction of the kidney-brain axis during the aging process. Our
      previous study showed that the downregulation of Klotho was involved in aging
      related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8)
      mice. The present study investigated the potential role of Klotho in aging
      associated inflammation and renal injury. METHODS: Age- and gender-matched groups
      of SAMP8 mice and their corresponding normal control senescence-accelerated mouse
      resistant-1 (SAMR1) were used to investigate the potential role of Klotho in
      aging-associated inflammation and renal injury. RESULTS: Compared with aged SAMR1
      controls, early-stage chronic kidney disease (CKD), which is associated with an
      increase in the urinary albumin-to-creatinine ratio, inflammatory cell
      infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed
      in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced
      activation of the retinoic acid-inducible gene 1/nuclear factor-kappaB (RIG-I/NF
      kappaB) signaling pathway and subsequent production of the proinflammatory
      mediators tumor necrosis factor alpha, interleukin-6, and inducible nitric oxide
      synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls.
      CONCLUSIONS: The present results suggest that aging-related inflammation and the
      development of early-stage CKD are likely associated with the downregulation of
      Klotho and induction of the RIG-I/NF-kappaB signaling pathway in 12-month-old
      SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage
      may be a potential mouse model for investigating the kidney-brain axis in the
      aging process.

PMID- 25986238
TI  - Depressive symptomatology and cortisol concentrations in elderly community
      residents: a cross-sectional study.
AB  - BACKGROUND: Researches seek to understand the links between adverse health
      outcomes and cortisol concentrations. However, the relationship between
      depressive symptomatology and cortisol concentrations is controversial in the
      literature. AIM: To analyze the relationship between the depressive
      symptomatology and the cortisol concentrations in elderly community residents in
      the Brazilian Northeast. METHODS: Cross-sectional study is composed of 256
      elderly (>=65 years). Depressive symptomatology was evaluated by the Center for
      Epidemiologic Studies-Depression Scale and cortisol concentrations by salivary
      collection (upon waking, 30 and 60 min after waking, at 3 pm and before bed), in
      addition to composite measurements. Sociodemographic and health conditions were
      evaluated. For analysis of the cortisol measurements in relation to depressive
      symptomatology, and between genders, the Student's t test was used. For cortisol
      measurements in every curve, analysis of variance for repeated measurements with
      Bonferroni post hoc test was used. RESULTS: There were significant salivary
      cortisol differences upon awakening, among elderly with and without depressive
      symptomatology (p = 0.04). There was no significance in relation to gender.
      Between measurements of each curve, elderly with depressive symptomatology showed
      no significant difference between the 1st measure in relation to the 2nd and 3rd,
      and also between the 4th and 5th, demonstrating higher cortisol night levels in
      elderly with depressive symptomatology, without decline, with curve plane aspect.
      CONCLUSION: The relationship between depressive symptomatology and
      hypocortisolism throughout the day seems to exist. However, in Brazil, adverse
      life conditions can lead to chronic stress and be sufficient factors to superpose
      biggest differences that could exist in relation to the presence of depressive
      symptomatology.

PMID- 25986239
TI  - Ventilation in situ after cardiac death improves pulmonary grafts exposed to 2
      hours of warm ischemia.
AB  - BACKGROUND: The pulmonary donor pool would increase substantially if lungs could
      be donated after cardiac death (DCD). There have been ethical and legal obstacles
      since administration of heparin and cooling has to be done immediately after
      cardiac death. This study examines whether ventilation of DCD lungs without
      administering heparin or cooling the lungs after cardiac death could improve
      graft function. METHOD: Twelve donor pigs with a mean bodyweight of 70 kg were
      randomized into two groups. Six animals were ventilated in situ with 50% oxygen,
      4 L/min, and 5 cm H2O in positive end-expiratory pressure or PEEP for 2 h after
      cardiac death. Six animals served as non-ventilated controls and were exposed to
      warm ischemia for 2 h. After 2 h, all lungs were harvested and flush perfused
      with Perfadex((r)) solution and stored at 8 degrees C for another 2 h. An ex vivo
      lung perfusion or EVLP circuit was used for evaluation. RESULTS: Non-ventilated
      lungs developed pulmonary edema, and had highly impaired blood gas levels and a
      significantly increased weight. The ventilated lungs demonstrated excellent blood
      gas levels and unchanged weight. CONCLUSION: The increase in tolerable warm
      ischemic time in combination with avoiding heparinization and cooling might
      facilitate the use of DCD lungs for transplantation.

PMID- 25986240
TI  - Risk factors for saddle-related skin lesions on elephants used in the tourism
      industry in Thailand.
AB  - BACKGROUND: Lesions related to working conditions and improper saddle design are
      a concern for a variety of working animals including elephants. The objectives of
      the present study were to determine the prevalence of cutaneous lesions in
      anatomic regions (i.e., neck, girth, back, tail) in contact with saddle-related
      equipment among elephants in Thailand working in the tourism industry, and to
      identify potential risk factors associated with these lesions. Data for this
      cross-sectional study were collected between May 2007 and July 2007 on 194
      elephants from 18 tourism camps across Thailand. RESULTS: There was a high
      prevalence (64.4 %; 95 % CI 57.3 - 71.2) of active lesions, most often located on
      the back region. Using multilevel multivariable logistic regression modelling
      containing a random intercept for camp we identified the following risk factors:
      increasing elephant age, the use of rice sacks as padding material in contact
      with the skin, and the provision of a break for the elephants. Working hours had
      a quadratic relationship with the log odds of an active lesion where the
      probability of an active lesion initially increased with the number of working
      hours per day and then declined possibly reflecting a "healthy worker" bias where
      only animals without lesions continue to be able to work these longer hours.
      CONCLUSIONS: While we recognize that the cross-sectional nature of the study
      posed some inferential limitations, our results offer several potential
      intervention points for the prevention of these lesions. Specifically, we
      recommend the following until longitudinal studies can be conducted: increased
      monitoring of older elephants and the back region of all elephants, working less
      than 6 hours per day, and the avoidance of rice sacks as padding material in
      contact with skin.

PMID- 25986241
TI  - Construction of hybrid films of silver nanoparticles and polypyridine ruthenium
      complexes on substrates.
AB  - Hybrid films of functional molecules and metal nanoparticles have been considered
      to be novel photo-functional devices. Here we have successfully constructed
      hybrid films of silver nanoparticles and ruthenium polypyridine derivatives on
      substrates. In order to hybridise them on a surface, a self-assembled monolayer
      method via chemical bond formation and electro-reductive polymerisation (thick
      layers) via physical attachment have been employed. These methods have the
      advantage of convenient and reproducible fabrication of complicated hybrid films.
      Furthermore, it has been clarified that these hybrid films show unique photo
      functional behaviours, such as enhanced photocurrent generation. 

PMID- 25986242
TI  - Clinical Trials, Disparities, and Financial Burden: It's Time to Intervene.

PMID- 25986243
TI  - Male Breast Cancer: A Study in Small Steps.

PMID- 25986244
TI  - A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma.
AB  - LESSONS LEARNED: This study is a rare example of effective doses of both targeted
      agents being both administered and tolerated.This combination should not be used
      in melanoma. BACKGROUND: Sorafenib and bortezomib affect BCL family member
      expression. We previously demonstrated that bortezomib augmented sorafenib
      mediated cytotoxicity in melanoma cell lines in vitro. We aimed to combine
      sorafenib 400 mg b.i.d. with increasing doses of weekly bortezomib. METHODS:
      Patients with metastatic melanoma were enrolled in dose-escalation cohorts to
      determine the maximum tolerated dose (MTD) of sorafenib (twice daily) in
      combination with bortezomib (weekly for 3 of 4 weeks). The MTD was defined as the
      highest dose level at which less than 33% of patients exhibited a dose-limiting
      toxicity (DLT). Efficacy, as measured by 6-month progression-free survival and
      response rate per RECIST, was documented. RESULTS: Eleven patients were enrolled
      at three dose levels. DLTs (fatigue and rash) were seen in two of three patients
      at the highest dose level. Five patients were enrolled for sorafenib 400 mg
      b.i.d. and bortezomib 1.0 mg/m(2) weekly for 3 of every 4 weeks; none had DLTs,
      and this dose level was defined as the MTD. Of 10 evaluable patients, no
      responses were seen. Two of 11 patients (18%) remained progression free for
      longer than 6 months. CONCLUSION: The combination of sorafenib and bortezomib is
      safe but not active in patients with melanoma.

PMID- 25986245
TI  - Recognizing the Financial Burden of Cancer Patients in Clinical Trials.

PMID- 25986247
TI  - [Submammary thrombophlebitis, a not so uncommon condition].

PMID- 25986246
TI  - 6-OHDA-Induced Changes in Parkinson's Disease-Related Gene Expression are not
      Affected by the Overexpression of PGAM5 in In Vitro Differentiated Embryonic
      Mesencephalic Cells.
AB  - LUHMES cells, a recently established line of immortalized embryonic mesencephalic
      cells, are the novel in vitro model for studying Parkinson's disease (PD) and
      dopaminergic neuron biology. Phosphoglyceromutase 5 (PGAM5) is a mitochondrial
      protein involved in mitophagy, mitochondria dynamics, and other processes
      important for PD pathogenesis. We tested the impact of lentiviral overexpression
      of PGAM5 protein in LUHMES cells on their differentiation and expression of 84 PD
      related genes. LUHMES cells were transduced with PGAM5 or mock and treated with
      100 MUM 6-hydroxydopamine (6-OHDA), a model PD neurotoxin. Real-Time PCR analysis
      revealed that the treatment with 6-OHDA-induced changes in expression of 44 PD
      related genes. PGAM5 transduction alone did not cause alternations in PD-related
      genes expression, nor it affected changes in gene expression mediated by 6-OHDA.
      The 6-OHDA-induced PD-related gene expression profile of LUHMES cells is
      presented for the first time and widely discussed.

PMID- 25986248
TI  - Expression of a single siRNA against a conserved region of NP gene strongly
      inhibits in vitro replication of different Influenza A virus strains of avian and
      swine origin.
AB  - Influenza A virus is the principal agent responsible of the respiratory tract's
      infections in humans. Every year, highly pathogenic and infectious strains with
      new antigenic assets appear, making ineffective vaccines so far developed. The
      discovery of RNA interference (RNAi) opened the way to the progress of new
      promising drugs against Influenza A virus and also to the introduction of disease
      resistance traits in genetically modified animals. In this paper, we show that
      Madin-Darby Canine Kidney (MDCK) cell line expressing short hairpin RNAs (shRNAs)
      cassette, designed on a specific conserved region of the nucleoprotein (NP) viral
      genome, can strongly inhibit the viral replication of four viral strains sharing
      the target sequence, reducing the viral mRNA respectively to 2.5*10(-4), 7.5*10(
      5), 1.7*10(-3), 1.9*10(-4) compared to the control, as assessed by real-time PCR.
      Moreover, we demonstrate that during the challenge with a viral strain bearing a
      single mismatch on the target sequence, although a weaker inhibition is observed,
      viral mRNA is still lowered down to 1.2*10(-3) folds in the shRNA-expressing
      clone compared to the control, indicating a broad potential use of this approach.
      In addition, we developed a highly predictive and fast screening test of siRNA
      sequences based on dual-luciferase assay, useful for the in vitro prediction of
      the potential effect of viral inhibition. In conclusion, these findings reveal
      new siRNA sequences able to inhibit Influenza A virus replication and provide a
      basis for the development of siRNAs as prophylaxis and therapy for influenza
      infection both in humans and animals. 

PMID- 25986249
TI  - Inhibitors of cellular kinases with broad-spectrum antiviral activity for
      hemorrhagic fever viruses.
AB  - Host cell kinases are important for the replication of a number of hemorrhagic
      fever viruses. We tested a panel of kinase inhibitors for their ability to block
      the replication of multiple hemorrhagic fever viruses. OSU-03012 inhibited the
      replication of Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382
      dihydrochloride inhibited Lassa, Ebola and Marburg viruses. BIBX 1382 blocked
      both Lassa and Ebola virus glycoprotein-dependent cell entry. These compounds may
      be used as tools to understand conserved virus-host interactions, and implicate
      host cell kinases that may be targets for broad spectrum therapeutic
      intervention. 

PMID- 25986250
TI  - Expression of Aurora-B and FOXM1 predict poor survival in patients with
      nasopharyngeal carcinoma.
AB  - PURPOSE: The purpose of this work was to investigate the relationship between
      Aurora-B, FOXM1, and clinical outcomes in patients with nasopharyngeal carcinoma
      (NPC) who were treated with a combination of induction chemotherapy and
      radiotherapy. PATIENTS AND METHODS: The expression of Aurora-B and FOXM1 were
      investigated by immunohistochemistry using a tissue microarray (TMA) containing
      samples from 166 NPC patients who were treated with cisplatin (DDP) +
      fluorouracil (5-FU) induction chemotherapy and radiotherapy between 1999 and
      2005. The relationship of Aurora-B, FOXM1, and survival of these NPC patients was
      analyzed. RESULTS: Informative TMA results were obtained in 91 tumor cases for
      Aurora-B and 93 tumor cases for FOXM1. The 8-year failure-free survival rate
      (FFS) for the Aurora-B-negative and Aurora-B-positive group was 65.6 and 37.3%,
      respectively (p = 0.024), and the 8-year distant FFS (D-FFS) rate was 65.6 and
      41.5%, respectively (p = 0.047). The 8-year overall survival (OS) in the FOXM1
      negative group was moderately higher than in the FOXM1-positive group (58.4 vs
      39.1%, p = 0.081). Cox regression analysis revealed that for FFS, Aurora-B
      expression was a significant prognostic factor (p = 0.025), while for D-FFS,
      Aurora-B expression was a marginally significant prognostic factor (p = 0.056).
      When FOXM1 expression was analyzed, the Cox regression analyses showed that FOXM1
      expression was a marginally significant prognostic factor (p = 0.056) for OS.
      Correlation analysis showed that Aurora-B and FOXM1 expression had no significant
      correlation. CONCLUSION: Aurora-B and FOXM1 were both adverse prognostic markers
      for NPC patients treated with chemoradiotherapy. However, the two markers had no
      significant correlation.

PMID- 25986251
TI  - Consensus and differences in primary radiotherapy for localized and locally
      advanced prostate cancer in Switzerland: A survey on patterns of practice.
AB  - INTRODUCTION: External beam radiotherapy (EBRT), with or without androgen
      deprivation therapy (ADT), is an established treatment option for nonmetastatic
      prostate cancer. Despite high-level evidence from several randomized trials, risk
      group stratification and treatment recommendations vary due to contradictory or
      inconclusive data, particularly with regard to EBRT dose prescription and ADT
      duration. Our aim was to investigate current patterns of practice in primary EBRT
      for prostate cancer in Switzerland. MATERIALS AND METHODS: Treatment
      recommendations on EBRT and ADT for localized and locally advanced prostate
      cancer were collected from 23 Swiss radiation oncology centers. Written
      recommendations were converted into center-specific decision trees, and analyzed
      for consensus and differences using a dedicated software tool. Additionally,
      specific radiotherapy planning and delivery techniques from the participating
      centers were assessed. RESULTS: The most commonly prescribed radiation dose was
      78 Gy (range 70-80 Gy) across all risk groups. ADT was recommended for
      intermediate-risk patients for 6 months in over 80 % of the centers, and for high
      risk patients for 2 or 3 years in over 90 % of centers. For recommendations on
      combined EBRT and ADT treatment, consensus levels did not exceed 39 % in any
      clinical scenario. Arc-based intensity-modulated radiotherapy (IMRT) is
      implemented for routine prostate cancer radiotherapy by 96 % of the centers.
      CONCLUSION: Among Swiss radiation oncology centers, considerable ranges of
      radiotherapy dose and ADT duration are routinely offered for localized and
      locally advanced prostate cancer. In the vast majority of cases, doses and
      durations are within the range of those described in current evidence-based
      guidelines.

PMID- 25986252
TI  - Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing
      ablation for atrial fibrillation.
AB  - OBJECTIVE: Uninterrupted oral warfarin strategy has become the standard protocol
      to prevent complications during catheter ablation (CA) for the treatment of
      atrial fibrillation (AF). However, little is known about the safety and efficacy
      of uninterrupted dabigatran therapy in patients undergoing CA for AF. Therefore,
      this study investigated the safety and efficacy of uninterrupted dabigatran
      therapy and compared the findings with those for uninterrupted warfarin therapy.
      METHODS: Bleeding and thromboembolic events during the periprocedural period were
      evaluated in 363 consecutive patients who underwent CA for AF at Nagoya
      University Hospital, and received uninterrupted dabigatran (n=173) or
      uninterrupted warfarin (n=190) for periprocedural anticoagulation. RESULTS: A
      total of 27 (7%) patients experienced either bleeding or thromboembolic
      complications. Major bleeding complications occurred in 2 (1%) patients in the
      dabigatran group (DG) and 2 (1%) patients in the warfarin group (WG). Eight (5%)
      patients in the DG and 9 (5%) patients in the WG experienced groin hematoma, a
      type of minor bleeding complication. Meanwhile, no patient in the DG and 1 (1%)
      in the WG developed cerebral ischemic stroke. Overall, there was no significant
      difference between the groups for any category. The activated partial
      thromboplastin time (APTT) independently predicted periprocedural complications
      in the DG. CONCLUSION: Uninterrupted dabigatran therapy in CA for AF thus may be
      a safe and effective anticoagulant therapy, and appears to be closely similar to
      continuous warfarin; however, it is essential to pay close attention to the APTT
      values when using dabigatran during CA.

PMID- 25986253
TI  - Frequency characteristics and associations with the defibrillation threshold of
      ventricular fibrillation in patients with implantable cardioverter
      defibrillators.
AB  - OBJECTIVE: The dominant frequency (DF) in frequency analyses is considered to
      represent the objective cycle length and complexity of activation under
      conditions of ventricular fibrillation (VF). However, knowledge regarding the
      mechanisms determining the DF in human VF is limited. We studied the
      characteristics of the DF of human VF and relationship between DF and the
      defibrillation threshold. METHODS: Seventy-two implantable cardioverter
      defibrillator patients and 211 VF were studied. Using defibrillation tests, we
      performed a frequency analysis with fast Fourier transformation. The correlations
      between DF and clinical characteristics, including the defibrillation threshold,
      were assessed. RESULTS: The mean DF of all induced VFs was 5.2+/-0.8 Hz. The
      patients were divided into two groups according to DF: the low-DF (DF <5.2 Hz,
      n=32) and high-DF (DF >=5.2 Hz, n=40) groups. The frequency of structural heart
      disease was significantly higher in the low-DF group. In addition, the QRS
      duration, QT interval and effective refractory period of the right ventricle (RV
      ERP) were significantly longer in the low-DF group. A multivariate analysis
      showed RV-ERP to be the only independent predictor of DF. Excluding patients
      receiving group III anti-arrhythmic drugs, which are known to have potent
      defibrillation threshold effects, the defibrillation threshold was significantly
      lower in the low-DF group (p=0.026). CONCLUSION: We found that the DF of human VF
      is associated with underlying heart disease, the cardiac function, cardiac
      conduction, ventricular refractoriness and defibrillation threshold. Our findings
      may be useful for identifying and managing patients with a high defibrillation
      threshold.

PMID- 25986254
TI  - Breath Sound Intensity during Tidal Breathing in COPD Patients.
AB  - OBJECTIVE: There is a discrepancy in the intensity of breath sounds in chronic
      obstructive pulmonary disease (COPD) patients between subjective studies, which
      have reported a diminished intensity, and objective studies using airflow
      standardized measurements, which have not demonstrated a diminished intensity. We
      herein evaluated the breath sound intensity in COPD patients during tidal
      breathing in order to obtain clinically relevant results. METHODS: The subjects
      included 20 stable COPD patients and 20 normal controls. Microphones were
      attached to six sites on the chest wall, and breath sounds at the chest wall and
      airflow in the mouth were measured during resting tidal and deep tidal breathing.
      The octave-band power values of the breath sounds were subsequently calculated.
      RESULTS: 1. During resting breathing, the intensity of breath sounds during both
      inspiration and expiration was significantly greater in the COPD group than in
      the control group; the difference was prominent at higher frequency bands (>400
      Hz). In addition, the power of the high frequency bands tended to be positively
      correlated with the CT visual emphysema scores but not the forced expiratory
      volume in one second, The airflow during resting breathing did not differ between
      the two groups. 2. During deep breathing, the intensity of inspiratory breath
      sounds at the dominant frequency band (200-400 Hz) was diminished over the upper
      and middle lung fields in the COPD group compared to that observed in the control
      group, while the intensity during expiration was not. The airflow during deep
      breathing was lower in the COPD group than in the control group. CONCLUSION: In
      the present study, the breath sound intensity in the COPD patients was diminished
      during deep inspiration due to a reduced airflow and increased during both
      resting inspiration and expiration.

PMID- 25986255
TI  - The Importance of Stabilizing PaCO2 during Long-term Non-invasive Ventilation in
      Subjects with COPD.
AB  - OBJECTIVE: In subjects with chronic obstructive pulmonary disease (COPD), the
      effect of partial pressure of CO2 (PaCO2) alterations during long-term non
      invasive ventilation (NIV) on continuance remains uncertain. We herein
      investigated the utility of PaCO2 stability during long-term NIV as a prognostic
      outcome. METHODS: We retrospectively assessed data from 54 subjects with COPD who
      received long-term NIV. The annual alteration in PaCO2 during NIV was determined
      using a simple linear regression method for each subject who had at least two 6
      month intervals of PaCO2 data. Annual alterations in PaCO2 during long-term NIV
      and probable confounders were examined, and long-term NIV discontinuation was the
      major outcome. RESULTS: Data from 37 subjects who met the criteria were analyzed.
      PaCO2 during long-term NIV increased slightly in 19 subjects (group 1, <2 mm
      Hg/y), and increased greatly in 18 subjects (group 2, >2 mmHg/y). In the
      multivariate modality model, smaller annual alterations in PaCO2 (p=0.009) and
      lower PaCO2 6 months after the start of long-term NIV (6 m-PaCO2) (p=0.03) were
      associated with a significantly higher probability of continuing NIV. The 2- and
      5-year probabilities of continuing NIV were 89% and 66% for group 1 and 78% and
      32% for group 2, respectively. CONCLUSION: A lower 6 m-PaCO2 and a lower annual
      alteration of PaCO2 during long-term NIV are significant predictive variables for
      patients with COPD.

PMID- 25986256
TI  - Safety of a Pandemic Influenza Vaccine and the Immune Response in Patients with
      Duchenne Muscular Dystrophy.
AB  - OBJECTIVE: To examine the safety of and immune response to the influenza
      A(H1N1)pdm09 vaccine in patients with Duchenne muscular dystrophy (DMD). METHODS:
      Forty-four non-ambulatory patients with DMD hospitalized in a muscle disease ward
      and 41 healthy healthcare workers each received one dose of the influenza
      A(H1N1)pdm09 vaccine. Serum samples were collected before and four weeks after
      vaccination to measure the hemagglutinin inhibition antibody titers. RESULTS: No
      severe adverse events were noted in any of the subjects. The immune responses of
      the patients were comparable to those of the healthcare workers. Among the
      patients, tube feeding and a lower total protein level in the serum were
      identified to be significantly associated with a lower immune response.
      CONCLUSION: A single dose of the vaccine was found to be safe and induced an
      optimal level of immunity in the DMD patients. The nutritional status may be
      associated with the immune response in patients with DMD.

PMID- 25986257
TI  - Chemotherapy treatment of a pregnant woman with progressive gastric cancer.
AB  - We herein describe a rare case of gastric cancer that was treated with
      chemotherapy during pregnancy. A woman in her thirty's at 23 weeks of gestation
      was admitted to the hospital with epigastralgia and left cervical lymph node
      swelling. She had been previously diagnosed with metastatic adenocarcinoma at
      another hospital. Findings from a CT scan and esophagogastroduodenoscopy revealed
      progressive gastric cancer, and the pathology indicated poorly differentiated
      adenocarcinoma. Chemotherapy was administered at 24 weeks of gestation, without
      the development of severe toxicity. At 32 weeks of gestation, a healthy baby girl
      (birth weight 1,442 g, Apgar score 7/8) was delivered by caesarean section. The
      child continued to show no abnormalities at 12 months after delivery. 

PMID- 25986258
TI  - Immunological analysis of a patient with hepatitis B virus (HBV) reactivation
      after bone marrow transplantation.
AB  - Patients with resolved hepatitis B virus (HBV) infection undergoing chemo- or
      immunosuppressive therapy are at potential risk for HBV reactivation. To
      determine whether the host immune response contributes to liver injury, we
      performed an immunological analysis of a patient with HBV reactivation.
      Consistent with the detection of HBV DNA in the sera, the number of polyclonal
      HBV-specific cytotoxic T lymphocytes (CTLs) gradually increased; however, the
      number of CD4(+)CD25(+) regulatory T cells (Treg) decreased. The interaction
      between HBV-specific CTLs and CD4(+)CD25(+) Treg is an important determinant of
      liver injury during HBV reactivation. Therefore, monitoring the number of these
      cells might be a useful modality for the diagnosis of acute hepatitis resulting
      from HBV reactivation. 

PMID- 25986259
TI  - Drug-induced Liver Injury with HHV-6 Reactivation.
AB  - Liver dysfunction was identified in a 16-year-old boy hospitalized with high
      fever and abdominal pain and fullness. He had received pharmacotherapy for a
      headache 2 months previously and other drugs for a high fever 4 days prior to
      being admitted to our hospital. The patient's liver dysfunction was consistent
      with and fulfilled the criteria for drug induced liver injury, but the laboratory
      findings showed elevated procalcitonin levels, hyponatremia and leukocytosis.
      Moreover, we confirmed the presence of human herpesvirus 6 (HHV-6) DNA. The
      patient exhibited symptoms of high fever and abdominal pain and fullness but no
      exanthema. The clinical and laboratory findings did not satisfy the criteria for
      drug-induced hypersensitivity syndrome, and we speculate that the diversity of
      clinical and laboratory findings may have resulted from HHV-6 reactivation. To
      the best of our knowledge, this is the first case report on drug-induced liver
      injury with various findings due to HHV-6 reactivation. HHV-6 reactivation should
      be considered in patients with drug induced liver injury even in the absence of
      exanthema. 

PMID- 25986260
TI  - Brugada syndrome combined with monomorphic ventricular tachycardia and
      atrioventricular nodal reentrant tachycardia.
AB  - A 41-year-old man developed sustained monomorphic ventricular tachycardia (VT)
      with a left bundle branch block and inferior axis pattern during treadmill
      exercise concomitantly with unmasking of the typical Brugada electrocardiography
      (ECG) pattern. The typical ECG phenotype was provoked by a class IC drug. VT was
      not inducible with programmed electrical stimulation, but premature ventricular
      beat and non-sustained VT with the same morphology increased in frequency with
      isoproterenol treatment. Additionally, atrioventricular nodal reentrant
      tachycardia (AVNRT) was induced by electrical stimulation and VT and AVNRT were
      treated by radiofrequency catheter ablation. 

PMID- 25986261
TI  - Isoniazid-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
      Syndrome Presenting as Acute Eosinophilic Myocarditis.
AB  - It has been reported that hypereosinophilic syndrome may be induced by
      antituberculosis drugs. We herein report the case of a 43-year-old man who had
      been on antituberculosis drugs for two months to treat tuberculous meningitis.
      During therapy, he suffered from drug rash with eosinophilia and systemic
      symptoms (DRESS) presenting as acute eosinophilic myocarditis, as confirmed on a
      histopathologic examination. According to the patient's medication history,
      clinical features and accessory examination findings, the eosinophilic
      myocarditis was thought to be possibly induced by isoniazid. Although further
      investigations are needed to confirm causality, isoniazid may be added to the
      list of drugs with the potential to cause DRESS syndrome. 

PMID- 25986262
TI  - Pericardial Involvement in IgG4-related Disease.
AB  - We herein report the case of a 65-year-old man with pericardial involvement
      associated with autoimmune pancreatitis. Chest CT imaging showed pericardial
      thickening. The patient responded to corticosteroid therapy, and the pericardial
      thickening resolved. Multiple organs are involved in immunoglobulin G4 (IgG4)
      related disease (IgG4-RD); however, only a few cases of IgG4-related chronic
      constrictive pericarditis have been reported. To our knowledge, this is the first
      reported case of IgG4-RD with pericardial involvement at an early stage. This
      case indicates that recognizing pericardial complications in autoimmune
      pancreatitis is important and that CT imaging may be useful for obtaining the
      diagnosis and providing follow-up of pericardial lesions in cases of IgG4-RD. 

PMID- 25986263
TI  - Congenital Contractural Arachnodactyly without FBN1 or FBN2 Gene Mutations
      Complicated by Dilated Cardiomyopathy.
AB  - Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder
      characterized by marfanoid habitus with camptodactyly. However, cardiac features
      have rarely been documented in adults. We herein report a sporadic case of CCA in
      a 20-year-old woman who developed decompensated dilated cardiomyopathy. The
      patient did not have any mutations in the FBN1 or FBN2 genes, which are most
      commonly associated with Marfan syndrome and CCA, respectively. Although whether
      these two diseases are caused by a mutation(s) in the same gene or two different
      genes remains unknown, this case provides new clinical insight into the
      cardiovascular management of CCA. 

PMID- 25986264
TI  - Acute Renal Injury Induced by Hypersensitivity to Tolvaptan in an Elderly Patient
      with Congestive Heart Failure.
AB  - Tolvaptan (TLV) is a new vasopressin type 2 receptor antagonist effective in
      patients with heart failure (HF). We herein describe the case of an 84-year-old
      woman who developed acute renal injury induced by hypersensitivity to TLV. The
      patient had received an implanted pacemaker and was diagnosed with exacerbation
      of chronic HF due to atrial fibrillation, mitral regurgitation, tricuspid
      regurgitation and left ventricular dyssynchrony. Treatment with tolvaptan
      increased the urine volume, improved the dyspnea and decreased the edema.
      However, the patient's renal function and hyperkalemia worsened, and the blood
      eosinophil count increased without signs of dehydration or hypotension. Positive
      findings on a drug-induced lymphocyte stimulation test for TLV were consistent
      with this diagnosis.

PMID- 25986266
TI  - IgG4-related Kidney Disease in Which the Urinalysis, Kidney Function and Imaging
      Findings Were Normal.
AB  - IgG4-related kidney disease (IgG4RKD) is recognized as a fibroinflammatory
      disease characterized by storiform fibrosis, lymphoplasmacytic infiltration and a
      high serum IgG4 level. A renal biopsy is necessary to diagnose IgG4RKD in
      patients without any lesions in other organs. Nephrologists typically perform
      renal biopsies in patients with abnormal urinalysis, such as proteinuria or
      hematuria, or renal failure. However, we experienced a patient with IgG4RKD
      without abnormalities in the urinalysis, renal function or imaging, who had
      severe interstitial lesions. We therefore propose that renal biopsies should be
      considered if patients do not show abnormal urinalysis findings and are suspected
      to have IgG4RKD. 

PMID- 25986265
TI  - Reversible hypopituitarism with pituitary tuberculoma.
AB  - A 50-year-old woman presented with a headache and nausea. A sellar and
      suprasellar mass was detected on MRI; the tumor was heterogeneously enhanced with
      gadolinium, and the pituitary stalk was slightly thickened. Laboratory tests
      revealed severe growth hormone, luteinizing hormone, follicle-stimulating hormone
      and thyroid-stimulating hormone deficiencies. A pathological examination of the
      tumor showed scattered granulomas with central necrosis and Langhans giant cells.
      Tuberculin skin and QuantiFERON TB-Gold tests (QFT-2G) were positive.
      Accordingly, we diagnosed the patient with pituitary tuberculoma presenting with
      pituitary dysfunction. Following treatment with antituberculous drugs, the
      pituitary hormone function normalized and the pituitary tuberculoma disappeared. 

PMID- 25986267
TI  - Infective Endocarditis Presenting as Acute Renal Failure and Unusual
      Complications.
AB  - Infective endocarditis can be a diagnostic challenge. Few cases have so far
      reported infective endocarditis presenting as renal failure. Pseudoaneurysms of
      the mitral-aortic intervalvular fibrosa and splenic abscess are rare
      complications of infective endocarditis. We herein report a case of an 80-year
      old man admitted due to anorexia, malaise, edema of the legs and renal failure. A
      progressive degradation of the patient's renal function was documented and
      hemodialysis was started. Blood cultures revealed the presence of Enterococcus
      faecalis, and the patient was treated with ampicillin and gentamicin. The
      transesophageal echocardiogram findings showed pseudoaneurysms of the mitral
      aortic intervalvular fibrosa and in the aortic root wall. Due to abdominal pain,
      an abdominal CT scan was performed and showed a cystic lesion compatible with
      splenic abscess. The patient received 6 weeks of antibiotic treatment. There was
      progressive clinical improvement and regression of the splenic abscess, but no
      recovery of the renal function. This report illustrates an unusual clinical
      presentation of infective endocarditis with unusual complications that were
      successfully treated with antibiotics.

PMID- 25986268
TI  - Successful Detection of Renal Involvement in Sjogren's Syndrome Secondary to
      Systemic Lupus Erythematosus by Renal Biopsy.
AB  - An 80-year-old man presented with a mildly decreased renal function and increased
      anti-double-stranded-DNA (anti-dsDNA) antibody levels, and met the diagnostic
      criteria of the American College of Rheumatology for systemic lupus erythematosus
      (SLE). However, the incremental increase in creatinine levels and the mild
      proteinuria were inconsistent with lupus nephritis. We performed a renal biopsy,
      which revealed interstitial nephritis and minor glomerular abnormalities. Further
      examinations determined that the renal lesion was due to Sjogren's syndrome
      secondary to SLE. Following treatment with oral prednisolone, the patient's renal
      function improved as his anti-dsDNA antibody levels decreased. This case report
      indicates that renal biopsy should be considered even in elderly individuals when
      it may assist in the diagnosis, treatment, and prognosis of the patient.

PMID- 25986269
TI  - Non-Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency that
      Developed into Symptomatic Severe Hyponatremia.
AB  - A 78-year-old woman diagnosed with non-classic congenital adrenal hyperplasia due
      to 21-hydroxylase deficiency had been under glucocorticoid replacement therapy
      since the age of 17 years. After several weeks of suffering from gastroenteritis
      with vomiting, she presented with disturbance of consciousness, hypotension,
      dehydration, and severe hyponatremia (108 mEq/L) and a markedly increased serum
      vasopressin concentration (45.5 pg/mL). She regained consciousness after
      correcting her body-fluid balance with hypertonic saline and intravenous
      hydrocortisone sodium therapy. Her hyponatremia was likely caused by extra-renal
      sodium loss and impaired water excretion induced by an increase of serum
      vasopressin due to volume depletion and glucocorticoid deficiency.

PMID- 25986270
TI  - Neuroendocrine carcinoma arising in a mediastinal teratoma with pulmonary
      metastasis: a case report and the chemotherapy response.
AB  - Neuroendocrine carcinoma as a somatic-type malignancy (STM) arising in an
      extragonadal teratoma is extremely rare. The effect of chemotherapy has been
      poorly evaluated in such cases contrary to teratomas with other STMs. We herein
      demonstrate that systemic chemotherapy may be beneficial in a case of
      neuroendocrine carcinoma arising in a mediastinal teratoma with pulmonary
      metastasis. A 31-year-old man presented with mediastinal widening visualized on a
      chest radiograph. Computed tomography showed a huge mediastinal mass with two
      pulmonary nodules. Surgical resection confirmed the presence of a neuroendocrine
      carcinoma arising in a mediastinal teratoma and pulmonary metastasis. The patient
      subsequently received chemotherapy and has had no recurrence during the 28-month
      follow-up. 

PMID- 25986271
TI  - Neurological Symptoms of Sarcoidosis-induced Small Fiber Neuropathy Effectively
      Relieved with High-dose Steroid Pulse Therapy.
AB  - A 59-year-old woman was admitted to our hospital for an evaluation of a 10-day
      history of progressive pain and hypoesthesia of the right lower back associated
      with fever and constipation. Sarcoidosis was confirmed on mediastinal lymph node
      and skin biopsies. Although the neurological symptoms were suspected due to
      sarcoidosis-induced nerve dysfunction, nerve conduction studies and other routine
      examinations did not show any abnormalities. The intraepidermal nerve fiber
      density assessed on a skin biopsy was significantly reduced, suggesting small
      fiber neuropathy (SFN). The patient was finally diagnosed with sarcoidosis
      induced SFN, and her neurological symptoms were effectively relieved with high
      dose steroid therapy. 

PMID- 25986272
TI  - Accurate flow cytometric gating of the large lymphocyte region is a powerful
      screening method for detecting hairy cell leukemia presenting with a low tumor
      burden.
AB  - Hairy cell leukemia typically presents with pancytopenia and often mimics
      aplastic anemia. Making an accurate diagnosis is crucial, as treatment with the
      purine analogues cladribine and pentostatin brings about durable complete
      remission in the majority of patients. Surface kappa and lambda flow cytometric
      analyses of peripheral blood or bone marrow are a powerful screening tool,
      although routine gating of the entire lymphocyte region may fail to show light
      chain restriction due to a low tumor burden. We herein demonstrate that accurate
      subgating of the large lymphocyte region is essential and recommend the
      application of this method in all cases of pancytopenia of unknown etiology. 

PMID- 25986273
TI  - Intravascular hemolytic anemia in a patient with antibodies related to meropenem.
AB  - A 76-year-old woman treated with meropenem developed intravascular hemolytic
      attacks. A direct antiglobulin test was positive for C3d and IgG, and drug
      dependent antibody testing indicated that the antibodies were indeed drug
      dependent and reacted with drug-treated RBCs and RBCs in the presence of the
      drug. To our knowledge, this is the first reported case in which the causative
      antibodies related to meropenem were identified. This case highlights the
      importance of maintaining a high level of suspicion for drug-induced immune
      hemolytic anemia in patients with explained hemolysis as well as conducting
      specialized serologic testing. 

PMID- 25986274
TI  - Choroid Plexus Metastasis of Follicular Thyroid Carcinoma Diagnosed due to
      Intraventricular Hemorrhage.
AB  - Choroid plexus metastasis (CPM) is extremely rare and originates most frequently
      from renal cell carcinoma (RCC). We herein report the case of a 58-year-old man
      who developed a solitary CPM lesion derived from follicular thyroid carcinoma in
      addition to intraventricular hemorrhage. Computed tomography revealed acute
      hydrocephalus as a result of the hemorrhage, and we planned endoscopic hematoma
      evacuation. Since it was too difficult to reach the hematoma, we considered the
      possibility of a neoplasm and performed a biopsy of the lesion, the results of
      which led to an accurate diagnosis of CPM in this case. We also review previous
      reports of CPM originating from thyroid carcinoma compared with RCC. 

PMID- 25986275
TI  - Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis Associated with
      Primary Biliary Cirrhosis: A Case Report and Literature Review.
AB  - We herein report a rare case of microscopic polyangiitis with primary biliary
      cirrhosis (PBC) and a literature review of six previously reported cases of PBC
      complicated by anti-neutrophil cytoplasmic antibody-associated vasculitis. Due to
      the scarcity of similar reports, it was not possible to establish a true overlap
      syndrome or casual association. When the biliary enzyme levels are elevated in
      patients with vasculitis, physicians should thus be mindful of the possible
      coexistence of these diseases. 

PMID- 25986276
TI  - Mycobacterium abscessus Pulmonary Infection under Treatment with Tocilizumab.
AB  - Although biological agents are of considerable benefit to patients with
      rheumatoid arthritis (RA), the potential for opportunistic infections is a
      critical issue. It is therefore important to achieve a balance between treatment
      efficacy and controlling opportunistic infection. We herein report the
      successfully managed case of a 53-year-old patient with RA who developed
      pulmonary Mycobacterium abscessus infection during treatment with tocilizumab and
      methotrexate.

PMID- 25986277
TI  - Patchy Cerebral Meningitis: Spatiotemporal Resolution Using Contrast-Enhanced
      FLAIR-MRI.

PMID- 25986278
TI  - Disseminated streptococcal endophthalmitis in two diabetic patients.

PMID- 25986279
TI  - Hepatic gas gangrene.

PMID- 25986280
TI  - Eagle's Syndrome Manifesting as Chronic Swallowing Pain.

PMID- 25986281
TI  - Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon
      citratus (DC.) Stapf extracts.
AB  - Cymbopogon citratus is a widely distributed perennial herb belonging to the
      Poaceae family and has been extensively consumed for its medicinal, cosmetic, and
      nutritional effects for centuries. A large number of reports have been published
      describing the pharmacological, biological, and therapeutic actions of this herb.
      In this review, we summarized the literatures on related studies (up to January,
      2014) that highlighted the pharmacologic and biological effects of the major
      phytochemicals isolated from C. citratus extracts and its essential oil. The
      components of the essential oils found in C. citratus have a similar
      pharmacokinetic properties, including absorption, distribution, metabolism, and
      excretion. They are quickly absorbed following oral, pulmonary, and dermal
      administration. Based on the published reports, it can also be inferred that,
      after absorption from the small intestine, some phytochemicals in C. citratus can
      undergo oxidation, glucuronidation, sulfation, and/or O-methylation. Excretion is
      through urine, feces and/or expired volatiles. The biotransformation reactions of
      C. citratus bioactive constituents are essential for its relatively safe
      consumption and therapeutic applications. The data available so far warrant
      further studies evaluating C. citratus pharmacokinetics. Reliable pharmacokinetic
      data in humans would be critical for a better understanding of the the systemic
      handling of C. citratus. 

PMID- 25986282
TI  - Enhancing ergosterol production in Pichia pastoris GS115 by overexpressing
      squalene synthase gene from Glycyrrhiza uralensis.
AB  - The present study was designed to determine the effects of copy number variations
      (CNVs) of squalene synthase 1(SQS1) gene on the mevalonate (MVA) pathway. SQS1
      gene from G. uralensis (GuSQS1) was cloned and over-expressed in Pichia pastoris
      GS115. Six recombinant P. pastoris strains containing different copy number of
      GuSQS1 were constructed. HPLC was used to assay the level of ergosterol in all
      transgenic P. pastoris strains containing GuSQS1. HPLC analysis showed that the
      contents of ergosterol in all of the transgenic P. pastoris containing GuSQS1
      were higher than that in the negative control. And with the increase of copy
      number of GuSQS1, the content of ergosterol showed an increasing-decreasing
      increasing pattern. The contents of ergosterol in 10-copy-GuSQS1 P. pastoris and
      47-copy-GuSQS1 P. pastoris were significantly higher than that in the rest
      recombinant P. pastoris strains. In conclusion, the CNVs of GuSQS1 influence the
      content of secondary metabolites in the MVA pathway. The present study provides a
      basis for over-expressing GuSQS1 and increasing the content of glycyrrhizin in G.
      uralensis cultivars. 

PMID- 25986283
TI  - Inhibition of HMG-CoA reductase by MFS, a purified extract from the fermentation
      of marine fungus Fusarium solani FG319, and optimization of MFS production using
      response surface methodology.
AB  - The present study was designed to isolate and characterize a purified extract
      from Fusarium solani FG319, termed MFS (Metabolite of Fusarium solani FG319) that
      showed anti-atherosclerosis activity by inhibiting 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase. Response surface methodology (RSM) was employed
      to achieve an improved yield from the fermentation medium. The inhibiting effect
      of the isolate, MFS, on HMG-CoA reductase was greater than that of the positive
      control, lovastatin. The average recovery of MFS and the relative standard
      deviation (RSD) ranged between 99.75% to 101.18%, and 0.31% to 0.74%,
      respectively. The RSDs intra- and inter-assay of the three samples ranged from
      0.288% to 2.438%, and from 0.934% to 2.383%, respectively. From the RSM, the
      concentration of inducer, cultivation time, and culture temperatures had
      significant effects on the MFS production, with the effect of inducer
      concentration being more pronounced that other factors. In conclusion, the
      optimal conditions for the MFS production were achieved using RSM and that MFS
      could be explored as an anti-atherosclerosis agent based on its ability to
      inhibit HMG-CoA reductase. 

PMID- 25986284
TI  - The polysaccharide isolated from Pleurotus nebrodensis (PN-S) shows immune
      stimulating activity in RAW264.7 macrophages.
AB  - A novel Pleurotus nebrodensis polysaccharide (PN-S) was purified and
      characterized, and its immune-stimulating activity was evaluated in RAW264.7
      macrophages. PN-S induced the proliferation of RAW264.7 cells in a dose-dependent
      manner, as determined by the MTT assay. After exposure to PN-S, the phagocytosis
      of the macrophages was significantly improved, with remarkable changes in
      morphology being observed. Flow cytometric analysis demonstrated that PN-S
      promoted RAW264.7 cells to progress through S and G2/M phases. PN-S treatment
      enhanced the productions of interleukin-6 (IL-6), nitric oxide (NO), interferon
      gamma (INF-gamma), and tumor necrosis factor-alpha (TNF-alpha) in the
      macrophages, with up-regulation of mRNA expressions of interleukin-6 (IL-6),
      inducible nitric oxide synthase (iNOS), interferon gamma(INF-gamma) and tumor
      necrosis factor-alpha (TNF-alpha) being observed in a dose-dependent manner, as
      measured by qRT-PCR. In conclusion, these results suggest that the purified PN-S
      can improve immunity by activating macrophages.

PMID- 25986285
TI  - Antiarrhythmic ionic mechanism of Guanfu base A--Selective inhibition of late
      sodium current in isolated ventricular myocytes from guinea pigs.
AB  - The present study was designed to determine the effects of Guanfu base A (GFA) on
      the late sodium current (INa.L), transient sodium current (INa.T), HERG current
      (IHERG), and Kv1.5 current (IKv1.5). The values of INa.L, INa.T, IHERG and IKv1.5
      were recorded using the whole-cell patch clamp technique. Compared with other
      channels, GFA showed selective blocking activity in late sodium channel. It
      inhibited INa.L in a concentration-dependent manner with an IC50 of (1.57 +/-
      0.14) MUmol . L(-1), which was significantly lower than its IC50 values of (21.17
      +/- 4.51) MUmol . L(-1) for the INa.T. The inhibitory effect of GFA on INa,L was
      not affected by 200 MUmol . L(-1) H2O2. It inhibited IHERG with an IC50 of (273
      +/- 34) MUmol . L(-1) and has slight blocking effect on IKv1.5, decreasing IKv1.5
      by only 20.6% at 200 MUmol . L(-1). In summary, GFA inhibited INa.L selectively
      and remained similar inhibition in presence of reactive oxygen species. These
      findings may suggest a novel molecular mechanism for the potential clinical
      application of GFA in the treatment of cardiovascular disorders.

PMID- 25986286
TI  - Anti-asthmatic effects of oxymatrine in a mouse model of allergic asthma through
      regulating CD40 signaling.
AB  - The aim of the study was to investigate the anti-asthmatic effects of oxymatrine
      (OXY) and the possible underlying mechanisms. The mouse asthma model was
      established by ovalbumin (OVA) intraperitoneal injection. A total of fifty mice
      were randomly assigned to five groups: control, OVA, OVA + dexamethasone (Dex, 2
      mg . kg(-1)), and OVA + OXY (40 mg . kg(-1)), and OVA + OXY (80 mg . kg(-1)),
      respectively. Histological studies were conducted by the hematoxylin and eosin
      (HE) staining, the levels of interleukin-4 (IL-4), interleukin-5 (IL-5),
      interleukin-13, and IgE were evaluated by enzyme-linked immunosorbent assay
      (ELISA), and the protein level of CD40 was analyzed by Western blotting. OXY
      inhibited OVA-induced increases in eosinophil count; the levels of IL-4, IL-5,
      IgE, and IL-13 were recovered. It also substantially inhibited OVA-induced
      eosinophilia in lung tissues and the expression of CD40 protein. These findings
      suggest that OXY may effectively ameliorate the progression of asthma and could
      be explored as a possible therapy for patients with allergic asthma.

PMID- 25986287
TI  - Synthesis and cytotoxic activities of E-resveratrol derivatives.
AB  - The present study was designed to synthesize derivatives of E-resveratrol and
      evaluate their cytotoxic activity in vitro. Different functional groups were
      conjugated with the phenolic hydroxyl group of E-resveratrol, and the double bond
      of E-resveratrol was reduced. The in vitro cytotoxicity of the synthetic
      derivatives was evaluated against three tumor cell lines (A549, LAC, and HeLa)
      using the MTT assay. Twenty-six E-resveratrol derivatives were synthesized and
      their structures were confirmed by (1)H NMR, MS, IR, and elemental analyses.
      Compounds 1-6, 12, 15-21, and 23-26 were reported for the first time. Among them,
      Compounds 1, 2, 4, 5, and 9-11, showed significant cytotoxicity against tumor
      cells; especially, Compound 1 showed an IC50 value of 4.38 MUmol . L(-1) in the
      A549 cells which was 15-fold more active than E-resveratrol; Compound 9 showed an
      IC50 value of 1.41 MUmol . L(-1) in the HeLa cell line which was 90-fold more
      active than E-resveratrol, and close to adriamycin. The structure-activity
      relationships were also investigated. Compounds 1, 2 and 9-11 may serve as
      potential lead compounds for the discovery of new anticancer drugs.

PMID- 25986288
TI  - Six new cytotoxic and anti-inflammatory 11, 20-epoxy-ent-kaurane diterpenoids
      from Isodon wikstroemioides.
AB  - The present study was designed to determine the chemical constituents of EtOAc
      extracts of the aerial parts of Isodon wikstroemioides. Compounds 1-8 were
      isolated and purified by normal-phase silica gel and reversed-phase C18silica gel
      column chromatography and HPLC. Their structures were elucidated by extensive
      spectroscopic methods. Most of them were evaluated for their in vitro
      cytotoxicity against human cancer HL-60, SMMC-7721, A-549, MCF-7, and SW-480
      cells and their inhibitory activity against nitric oxide (NO) production in LPS
      activated RAW264.7 macrophages. Among the eight 11, 20-epoxy-ent-kauranoids
      isolated, compounds 1-6 (isowikstroemins H-M) were new diterpenoids. Compounds 1,
      3, and 7 exhibited significant cytotoxicity with IC50 values ranging from (0.84
      +/- 0.02) to (4.09 +/- 0.34) MUmol . L(-1), while compounds 4 and 5 showed
      selective cytotoxicity. In addition, compounds 1, 3, 4, and 7 exhibited
      inhibitory activity against nitric oxide (NO) production in LPS-activated
      RAW264.7 macrophages. These results provide a basis for future development of
      these compounds as anti-cancer and anti-inflammatory agents.

PMID- 25986289
TI  - Diagnostic ion filtering strategy for chemical characterization of Guge Fengtong
      Tablet with high-performance liquid chromatography coupled with electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry.
AB  - The present study was designed to characterize the chemical constituents of Guge
      Fengtong Tablet (GGFTT). Based on the chromatographic retention behavior,
      fragmentation pathways of chemical components and the published literatures, a
      diagnostic ion filtering strategy with electrospray ionization quadrupole time-of
      flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) was established to identify
      the multiple bioactive constituents of GGFTT. The rapid identification of forty
      seven components, including 18 phenolic acids, 8 saponins, 14 gingerol-related
      compounds, and 7 diarylhepatonoids, was accomplished using this newly developed
      method. The coupling of HPLC-ESI-Q-TOF/MS with the diagnostic ion filtering
      strategy was useful and efficient for the in-depth structural elucidation of
      chemical compounds of GGFTT. 

PMID- 25986291
TI  - Evaluation of community pharmacy-based services for type-2 diabetes in an
      Indonesian setting: pharmacist survey.
AB  - BACKGROUND: Diabetes is an emerging chronic disease in developing countries.
      Currently the management of diabetes in developing countries is mainly hospital
      or clinic based. With burgeoning numbers of patients with diabetes, other models
      need to be evaluated for service delivery in developing countries. Community
      pharmacists are an important option for provision of diabetes care. Currently,
      data regarding practices of community pharmacists in diabetes care have been
      limited to developed countries. OBJECTIVES: To evaluate current community
      pharmacy-based services and perceived roles of pharmacists in type 2 diabetes
      care, and characteristics (pharmacist and pharmacy) associated with current
      practice. SETTING: Community pharmacies in a developing country setting
      (Surabaya, Indonesia). METHODS: A questionnaire was administered to pharmacists
      managing a random sample of 400 community pharmacies in Surabaya, Indonesia.
      Current practice and pharmacists' perceived roles were rated using Likert scales,
      whilst an open-ended question was used to identify priority roles. Logistic
      regression models determined characteristics associated with current practice.
      RESULTS: A response rate of 60% was achieved. Dispensing (100%) and education on
      how to use medications (72.6%) were common current pharmacy practices. More than
      50% of pharmacists were supportive towards providing additional services beyond
      dispensing. The highest priorities for services beyond dispensing were education
      on medications [i.e. directions for use (58.6%) and common/important adverse
      effects (25.7%)], education on exercise (36.5%), education on diet (47.7%), and
      monitoring medication compliance (27.9%). Facilitators identified were: being
      perceived as part of a pharmacist's role (for all priority services), pharmacies
      with more than 50 diabetes customers per month (for diet education), and
      pharmacists' involvement in diabetes training (for compliance monitoring). The
      key barrier identified was lower pharmacist availability (for diet education as
      well as compliance monitoring). CONCLUSIONS: Most community pharmacies in
      Surabaya, Indonesia have only provided a basic service of dispensing for type 2
      diabetes patients. Many pharmacists believed that they should extend their roles
      particularly regarding patient education and monitoring. The development of
      pharmacist professional roles would assist in managing the burgeoning burden of
      diabetes. The identified facilitators/barriers provide baseline data to support
      the development of community pharmacy-based diabetes services.

PMID- 25986290
TI  - Prevalence and predictors of potentially inappropriate medications among home
      care elderly patients in Qatar.
AB  - BACKGROUND: Older patients receiving home health care are particularly at risk of
      receiving potentially inappropriate medications compared to community-dwelling
      population. Data on appropriateness of prescribing in these patients is limited.
      OBJECTIVE: To investigate the prevalence, patterns and determinants of
      potentially inappropriate medications among elderly patients receiving Home
      Health Care Services in Qatar. SETTING: Home Health Care Services department in
      Hamad Medical Corporation-Qatar. METHODS: A cross-sectional study, conducted over
      a 3 months period. Patients 65 years and older, taking at least one medication
      and receiving home care services were included. Potentially inappropriate
      medications were identified and classified in accordance with the American
      Geriatrics Society 2012 Beers Criteria. MAIN OUTCOME MEASURE: Prevalence of
      potentially inappropriate medications using updated Beers criteria. RESULTS: A
      total of 191 patients (38.2%) had at least one potentially inappropriate
      medication. As per Beers criteria, 35% of medications were classified as
      medications to be avoided in older adults regardless of conditions and 9% as
      potentially inappropriate medications when used with certain diseases or
      syndromes. The majority of potentially inappropriate medications (56%) were
      classified as medications to be used with caution. The two leading classes of
      potentially inappropriate medications were antipsychotics (27.4%) and selective
      serotonin reuptake inhibitors (16%). Significant predictors of inappropriate
      prescribing were hypertension [adjusted OR 1.7; 95% CI (1.0, 2.8)], dementia
      [adjusted OR 2.0; 95% CI (1.2, 3.1)], depression [adjusted OR 21.6; 95% CI (2.8,
      168.4)], and taking more than ten prescribed medications [adjusted OR 1.9; 95% CI
      (1.3, 2.8)]. CONCLUSION: Prescribing potentially inappropriate medications is
      common among older adults receiving home health care services in Qatar, a finding
      that warrants further attention. Polypharmacy, hypertension, depression and
      dementia were significantly associated with potentially inappropriate
      prescribing.

PMID- 25986292
TI  - Effect of an obesity pamphlet on parental perception and knowledge of excess
      weight in their children: results of a randomised controlled trial.
AB  - ISSUES ADDRESSED: This study examined the effectiveness of a brief educational
      intervention in increasing parental knowledge of childhood obesity risk factors
      and ability to correctly identify their child's weight status. METHODS: Eighty
      parents were randomly allocated to an experimental group given an obesity
      pamphlet or a control group given a stress management pamphlet. A survey measured
      parents' knowledge about risk factors, cause and consequences of childhood
      obesity, and perception of their child's weight. RESULTS: Parents with overweight
      or obese children increased their understanding of childhood obesity immediately
      after receiving the intervention, but did not differ significantly on perception
      of their child's weight. CONCLUSION: The experimental intervention increased
      knowledge of health risks associated with childhood obesity in parents of
      overweight or obese children. Parental perception of their child's weight status
      did not improve, suggesting that other factors have a role to play. SO WHAT? The
      obesity pamphlet may be a useful tool in a multifaceted approach targeting
      childhood obesity.

PMID- 25986293
TI  - Determining the location of the internal maxillary artery on ultrasonography and
      unenhanced magnetic resonance imaging before orthognathic surgery.
AB  - The purpose of this study was to examine the efficacy of ultrasonography (US) and
      unenhanced magnetic resonance imaging (MRI) to determine the location of the
      internal maxillary artery (IMA) before orthognathic surgery. The study subjects
      were 19 patients (seven males and twelve females) with mandibular prognathism
      seen at the authors' institution between March 2012 and April 2013. The distance
      from the skin to the IMA (S-IMA) and the distance from the mandibular notch to
      the IMA (MN-IMA) were measured. Using the US and coronal MRI images, S-IMA(cl)
      and MN-IMA(cl) in the closed position and S-IMA(op) and MN-IMA(op) in the open
      position were measured at a total of four points in each cross-section. There
      were significant correlations between the distances measured on coronal MRI and
      US for all groups (P<0.05). A total of 35 (92%) IMAs were classified as clear and
      three (8%) as unclear based on the US findings. Regarding the location of the
      IMA, 37 of the 38 sides studied (97%) were of the lateral type, while only one
      (3%) was of the medial type. The results of this study indicate that US can be
      used effectively to determine the location of the IMA. 

PMID- 25986294
TI  - Self-management support intervention to control cancer pain in the outpatient
      setting: a randomized controlled trial study protocol.
AB  - BACKGROUND: Pain is a prevalent and distressing symptom in patients with cancer,
      having an enormous impact on functioning and quality of life. Fragmentation of
      care, inadequate pain communication, and reluctance towards pain medication
      contribute to difficulties in optimizing outcomes. Integration of patient self
      management and professional care by means of healthcare technology provides new
      opportunities in the outpatient setting. METHODS/DESIGN: This study protocol
      outlines a two-armed multicenter randomized controlled trial that compares a
      technology based multicomponent self-management support intervention with care as
      usual and includes an effect, economic and process evaluation. Patients will be
      recruited consecutively via the outpatient oncology clinics and inpatient
      oncology wards of one academic hospital and one regional hospital in the south of
      the Netherlands. Irrespective of the stage of disease, patients are eligible when
      they are diagnosed with cancer and have uncontrolled moderate to severe cancer
      (treatment) related pain defined as NRS>=4 for more than two weeks. Randomization
      (1:1) will assign patients to either the intervention or control group; patients
      in the intervention group receive self-management support and patients in the
      control group receive care as usual. The intervention will be delivered by
      registered nurses specialized in pain and palliative care. Important components
      include monitoring of pain, adverse effects and medication as well as graphical
      feedback, education, and nurse support. Effect measurements for both groups will
      be carried out with questionnaires at baseline (T0), after 4 weeks (T1) and after
      12 weeks (T2). Pain intensity and quality of life are the primary outcomes.
      Secondary outcomes include self-efficacy, knowledge, anxiety, depression and pain
      medication use. The final questionnaire contains also questions for the economic
      evaluation that includes both cost-effectiveness and cost-utility analysis. Data
      for the process evaluation will be gathered continuously over the study period
      and focus on recruitment, reach, dose delivered and dose received. DISCUSSION:
      The proposed study will provide insight into the effectiveness of the self
      management support intervention delivered by nurses to outpatients with
      uncontrolled cancer pain. Study findings will be used to empower patients and
      health professionals to improve cancer pain control. TRIAL REGISTRATION:
      NCT02333968 December 29, 2014.

PMID- 25986295
TI  - Yoga and health promotion, practitioners' perspectives at a Brazilian university:
      A pilot study.
AB  - The purpose of this paper is to present the results of the Program Yoga and
      Health Promotion offered to 18 participants, lecturers, workers and students of
      the State University of Campinas, Brazil. The program aimed at favoring well
      being in relation to their physical, emotional and mental condition.
      Practitioners completed the Measure Yourself Medical Outcome Profile to identify
      the symptoms and the perception of self-reported well-being, and the T test was
      applied to the results of the participants' profiles before and after the
      program. Narratives were used based on trigger phrases. Seven categories (self
      control; self-perception; well-being; body awareness; balance; mind-body;
      reflexivity), were identified through thematic analysis. The results were
      discussed according to the triangulation of methods. RESULTS: 14 participants
      scored better profiles, with a p-value <0.05. As regards the narratives, there
      were no negative perceptions about the yoga practice. IN CONCLUSION: yoga was a
      positive intervention for the group of participants.

PMID- 25986296
TI  - Massage therapy alone and in combination with meditation for breast cancer
      patients undergoing autologous tissue reconstruction: A randomized pilot study.
AB  - This study explored whether massage combined with meditation is more helpful than
      massage alone for women recovering from autologous tissue reconstruction after
      mastectomy for breast cancer. Forty patients were randomly assigned to either
      massage therapy or massage plus meditation on postoperative days 1 through 3.
      Outcome measures were 1) visual analog scale (VAS) scores for stress, anxiety,
      relaxation, insomnia, alertness, fatigue, tension, pain, mood, and energy, and 2)
      Perceived Stress Scale-14 scores. Nineteen patients in each group finished the
      study. Preintervention and postintervention mean total VAS scores improved
      significantly in both groups (P < .001), but no significant difference occurred
      between groups. 

PMID- 25986297
TI  - Development and efficacy of music therapy techniques within palliative care.
AB  - Music therapy is increasingly becoming an intervention used in palliative care
      settings around the globe. While the specialty of palliative care music therapy
      is relatively young having emerged in the late 1980s, there is a strong and
      growing body of evidence demonstrating its efficacy in assisting a variety of
      issues common at end-of-life. There are multiple music therapy techniques that
      are implemented with clients in palliative care and they can be categorized in
      four broad areas: receptive, creative, recreative and combined. These techniques
      will be presented with respect to their development by clinicians as supported by
      the descriptive and research literature. Information is also provided on the use
      of music therapy in facilitating the grieving and bereavement process. 

PMID- 25986301
TI  - Infection. Bacteriotherapy for recurrent C. difficile infection--spores to the
      rescue?

PMID- 25986304
TI  - Reduced cortical thickness, surface area in patients with chronic obstructive
      pulmonary disease: a surface-based morphometry and neuropsychological study.
AB  - Neural impairments accompanying chronic obstructive pulmonary disease (COPD) have
      received growing research attention. Previous neuroimaging studies exclusively
      used volumetric methods to measure cortical volume as a whole rather than
      focusing on anatomical and neuropathological distinct indices. Here we decomposed
      the cortical architecture into cortical thickness (CTh), surface area (SA), and
      gyrification, for the first time, to provide a more integrative profile of brain
      damage in COPD. Clinical T1-weighted MRI scans were acquired in 25 stable COPD
      patients (mean age 69) and 25 age-matched controls. Images were processed using
      surface-based morphometry to obtain cortical parameters enabling more accurate
      measurement in deep sulci and localized regional mapping. Demographic,
      physiological, and cognitive assessments were made and correlated with cortical
      indices. Compared to controls, COPD patients showed significantly reduced CTh
      broadly distributed in motor, parietal, and prefrontal cortices, together with
      more circumscribed SA reduction in dorsomedial prefrontal cortex and Broca's area
      (cluster-level P < 0.05 corrected). No abnormal gyrification was detected.
      Decreased CTh in parietofrontal networks strongly correlated with visuospatial
      construction impairment in COPD patients. Furthermore, thinner dorsolateral
      prefrontal cortex (DLPFC) best predicted poorer performance (r (2)  = 0.315, P =
      0.004), and was associated with lower arterial oxygen saturation. These data
      indicate that cortical thinning is a key morphologic feature associated with COPD
      that could be partly attributed to oxygen desaturation and contributes to COPD
      visual memory and drawing deficits. Surface-based morphometry provides valuable
      information concerning COPD, and could ultimately help us to characterize the
      neurodegenerative pattern and to clarify neurologic mechanisms underlying
      cognitive dysfunction in COPD patients.

PMID- 25986305
TI  - The role of TGFbeta superfamily members in the pathophysiology of endometriosis.
AB  - The transforming growth factor-beta (TGFbeta) superfamily comprises over 30
      dimeric proteins with conserved structures, which play important roles in the
      control of cellular proliferation, differentiation and apoptosis. These proteins
      are expressed and finely regulated in human endometrium during the menstrual
      cycle, which is consistent with their effects on endometrial cell proliferation
      and tissue remodeling. This review is focused on summarizing the role of key
      members of the TGFbeta superfamily in the pathophysiology of endometriosis.
      Evidence suggests that TGFbeta, activins, inhibins, nodal, bone morphogenetic
      proteins, growth differentiation factors, and anti-Mullerian hormone are produced
      by endometriotic lesions and could be involved in the establishment and
      progression of the disease. Their receptors and signaling pathways may also be
      altered in the presence of endometriosis and may be potential targets to the
      development of therapeutic agents. 

PMID- 25986303
TI  - Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies.
AB  - Over the past three decades, the detection of oesophageal mucosal eosinophils has
      transitioned from a biomarker of GERD to a diagnostic criterion for eosinophilic
      oesophagitis (EoE). In GERD, oesophageal eosinophils are considered part of the
      chronic inflammatory response to acid reflux, whereas the marked eosinophilia in
      EoE is viewed as a central feature of the immune response to ingested food and/or
      environmental antigen stimulation. Descriptions of a considerable subset of
      patients with symptomatic, endoscopic and histological findings of EoE that
      resolve with PPI therapy has led to confusion and controversy regarding the
      distinction of EoE from GERD. Study findings indicate that PPI-responsive
      oesophageal eosinophilia (PPI-REE) more closely resembles EoE than GERD, both
      from a clinical and immunological aspect. Although responsiveness to PPI therapy
      should not be utilized to exclude EoE, PPI therapy is effective at reducing
      oesophageal eosinophilia in ~40% of patients, and PPI therapy is both a safe and
      practical initial step in the management of patients with oesophageal
      eosinophilia. Ongoing studies elucidating the mechanism behind PPI-REE will
      improve our understanding and management of EoE. In this Review, the mechanisms
      and evidence that underlie the controversy in the distinction between GERD and
      EoE are evaluated. 

PMID- 25986306
TI  - High DHEAS/free testosterone ratio is related to better metabolic parameters in
      women with PCOS.
AB  - AIMS: To demonstrate the effects of DHEAS/free testosterone (DHEAS/FT) ratio on
      metabolic parameters in women with and without polycystic ovary syndrome (PCOS).
      METHODS: The data of 91 women with PCOS and 66 women in the control group were
      collected retrospectively. RESULTS: DHEAS/FT of the control group was higher than
      that of PCOS group (684.93 +/- 300.54 to 517.2 +/- 300.8, p < 0.001). DHEAS/FT
      correlated with BMI (r = -0.352, p = 0.001), WHR (r = -0.371, p = 0.0219), LDL (r
      = -0.227, p = 0.031), HOMA-IR (r = -0.36, p = 0.001) and FAI (r = -0.639, p =
      0.001) negatively and with HDL (r = 0.344, p = 0.001) and SHBG (r = 0.646, p =
      0.001) positively. In the control group, DHEAS/FT correlated with BMI (r = 
      0.334, p = 0.007), CRP (r = -0.297, p = 0.016) and FAI (r = -0.399, p = 0.01)
      negatively. CONCLUSIONS: High DHEAS/FT ratios are related to a better metabolic
      phenotype in women with PCOS and low levels can be used to detect women with PCOS
      that have a higher risk of metabolic problems.

PMID- 25986308
TI  - Using Transcriptional Signatures to Assess Immune Cell Function: From Basic
      Mechanisms to Immune-Related Disease.
AB  - Assessing human immune response remains a challenge as it involves multiple cell
      types in specific tissues. The use of microarray-based expression profiling as a
      tool for assessing the immune response has grown increasingly over the past
      decade. Transcriptome analyses provide investigators with a global perspective of
      the complex molecular and cellular events that unfold during the development of
      an immune response. In this review, we will detail the broad use of gene
      expression profiling to decipher the complexity of immune responses from disease
      biomarkers identification to cell activation, polarisation or functional
      specialisation. We will also describe how such data-driven strategies revealed
      the flexibility of immune function with common and specific transcriptional
      programme under multiple stimuli. 

PMID- 25986307
TI  - A Direct Interaction with RNA Dramatically Enhances the Catalytic Activity of the
      HIV-1 Protease In Vitro.
AB  - Though the steps of human immunodeficiency virus type 1 (HIV-1) virion maturation
      are well documented, the mechanisms regulating the proteolysis of the Gag and Gag
      Pro-Pol polyproteins by the HIV-1 protease (PR) remain obscure. One proposed
      mechanism argues that the maturation intermediate p15NC must interact with RNA
      for efficient cleavage by the PR. We investigated this phenomenon and found that
      processing of multiple substrates by the HIV-1 PR was enhanced in the presence of
      RNA. The acceleration of proteolysis occurred independently from the substrate's
      ability to interact with nucleic acid, indicating that a direct interaction
      between substrate and RNA is not necessary for enhancement. Gel-shift assays
      demonstrated the HIV-1 PR is capable of interacting with nucleic acids,
      suggesting that RNA accelerates processing reactions by interacting with the PR
      rather than the substrate. All HIV-1 PRs examined have this ability; however, the
      HIV-2 PR does not interact with RNA and does not exhibit enhanced catalytic
      activity in the presence of RNA. No specific sequence or structure was required
      in the RNA for a productive interaction with the HIV-1 PR, which appears to be
      principally, though not exclusively, driven by electrostatic forces. For a
      peptide substrate, RNA increased the kinetic efficiency of the HIV-1 PR by an
      order of magnitude, affecting both turnover rate (k(cat)) and substrate affinity
      (K(m)). These results suggest that an allosteric binding site exists on the HIV-1
      PR and that HIV-1 PR activity during maturation could be regulated in part by the
      juxtaposition of the enzyme with virion-packaged RNA.

PMID- 25986309
TI  - The Role of Packaging Sites in Efficient and Specific Virus Assembly.
AB  - During the life cycle of many single-stranded RNA viruses, including many human
      pathogens, a protein shell called the capsid spontaneously assembles around the
      viral genome. Understanding the mechanisms by which capsid proteins selectively
      assemble around the viral RNA amidst diverse host RNAs is a key question in
      virology. In one proposed mechanism, short sequences (packaging sites) within the
      genomic RNA promote rapid and efficient assembly through specific interactions
      with the capsid proteins. In this work, we develop a coarse-grained particle
      based computational model for capsid proteins and RNA that represents protein-RNA
      interactions arising both from nonspecific electrostatics and from specific
      packaging site interactions. Using Brownian dynamics simulations, we explore how
      the efficiency and specificity of assembly depend on solution conditions (which
      control protein-protein and nonspecific protein-RNA interactions) and the
      strength and number of packaging sites. We identify distinct regions in parameter
      space in which packaging sites lead to highly specific assembly via different
      mechanisms and others in which packaging sites lead to kinetic traps. We relate
      these computational predictions to in vitro assays for specificity in which
      cognate viral RNAs compete against non-cognate RNAs for assembly by capsid
      proteins. 

PMID- 25986310
TI  - Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and
      Recommendations From the EXTRIP Workgroup.
AB  - STUDY OBJECTIVE: Salicylate poisoning is a challenging clinical entity associated
      with substantial morbidity and mortality. The indications for extracorporeal
      treatments such as hemodialysis are poorly defined. We present a systematic
      review of the literature along with evidence- and consensus-based recommendations
      on the use of extracorporeal treatment in salicylate poisoning. METHODS: The
      Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup is a multidisciplinary
      group with international representation whose aim is to provide evidence-based
      recommendations on the use of extracorporeal treatments in poisoning. We
      conducted a systematic literature review followed by data extraction and
      summarized findings, following a predetermined format. The entire work group
      voted by a 2-round modified Delphi method to reach consensus on voting
      statements, using a RAND/UCLA Appropriateness Method to quantify disagreement.
      Anonymous votes were compiled, returned, and discussed in person. A second vote
      determined the final recommendations. RESULTS: Eighty-four articles met inclusion
      criteria, including 1 controlled clinical trial, 3 animal studies, and 80 case
      reports or case series, yielding an overall very low quality of evidence for all
      recommendations. Clinical data on 143 patients (130 sets of which could be
      analyzed for patient-level entry data), including 14 fatalities, were reviewed.
      Toxicokinetic data on 87 patients were also included. After the second round of
      voting, the workgroup concluded that salicylates are dialyzable by hemodialysis
      and hemoperfusion (level of evidence=B) and recommended extracorporeal treatment
      in patients with severe salicylate poisoning (1D), including any patient with
      altered mental status (1D), with acute respiratory distress syndrome requiring
      supplemental oxygen (1D), and for those in whom standard therapy is deemed to be
      failing (1D) regardless of the salicylate concentration. High salicylate
      concentrations warrant extracorporeal treatment regardless of signs and symptoms
      (>7.2 mmol/L [100 mg/dL] [1D]; and >6.5 mmol/L [90 mg/dL] [2D]), with lower
      thresholds applied for patients with impaired kidney function (>6.5 mmol/L [90
      mg/dL] [1D]; >5.8 mmol/L [80 mg/dL] [2D]). Extracorporeal treatment is also
      suggested for patients with severe acidemia (pH <=7.20 in the absence of other
      indications) (2D). Intermittent hemodialysis is the preferred modality (1D),
      although hemoperfusion (1D) and continuous renal replacement therapies (3D) are
      acceptable alternatives if hemodialysis is unavailable, as is exchange
      transfusion in neonates (1D). CONCLUSION: Salicylates are readily removed by
      extracorporeal treatment, with intermittent hemodialysis being the preferred
      modality. The signs and symptoms of salicylate toxicity listed warrant
      extracorporeal treatment, as do high concentrations regardless of clinical
      status.

PMID- 25986312
TI  - A special issue dedicated to a complex tissue.

PMID- 25986313
TI  - Expression profiles of human CCN genes in patients with osteoarthritis or
      rheumatoid arthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) are widespread
      disabling joint disorders that are considered to be polygenic in nature. This
      study investigated the spatial expression patterns of all six known human CCN
      genes using end-stage OA and RA joint samples. DESIGN: We performed in situ
      hybridization and histological analysis to investigate the spatial expression
      patterns of human CCN genes using joint tissues obtained during total knee and
      hip joint replacement procedures on patients with advanced OA or RA. Normal joint
      tissues taken while performing bipolar hip replacement surgeries were used as
      controls. RESULTS: All CCN genes were expressed at higher levels in OA and RA
      synovial samples as compared with normal controls. Whereas CCN3 and CCN6 were
      undetectable in control, OA, and RA cartilage, CCN1, CCN2, CCN4, and CCN5 were
      expressed to a greater extent in OA and RA knee cartilage. CONCLUSIONS: Our
      results indicate an involvement of several CCN genes in the pathophysiology of OA
      and RA.

PMID- 25986314
TI  - Effect of an anti-reflux medical device in the control of deflation cough: A
      placebo-controlled comparative study with an antacid drug in chronic coughers.
AB  - BACKGROUND: Deflation cough (DC), i.e. the cough-like expiratory expulsive
      efforts evoked by maximal lung emptying, is partially inhibited by prior intake
      of an antacid. We wished to compare the effects of an anti-reflux medical device
      (Gastrotuss((r))) and of a widely used antacid drug (Maalox((r))) on the number
      of expiratory thrusts evoked by maximal lung emptying in chronic cough patients.
      METHODS: Twenty consecutive chronic cough outpatients also presenting DC attended
      the clinic on three separate occasions and were requested to inhale to near total
      lung capacity and then exhale maximally for at least 6 s. Trained investigators
      detected aurally the number of cough efforts evoked by maximal lung emptying
      prior to and 1, 5, 10, 30 e 60 min after administration of either Maalox((r)), or
      Gastrotuss((r)) or placebo. The liking of the administered agents was also rated.
      RESULTS: In control conditions, maximal lung emptying was consistently
      accompanied by the appearance of DC. The number of efforts was unchanged after
      placebo whereas it was markedly (P < 0.001) reduced 1-10 min following
      Maalox((r)) and Gastrotuss((r)) administration. The value of liking for
      Gastrotuss((r)) was greater (P < 0.01) than those of Maalox((r)) and placebo.
      CONCLUSIONS: Pre-treatment with anti-reflux agents with a substantially different
      composition are equally effective in inhibiting DC. The liking of the two
      compounds used in the present experiments differed considerably and may be
      important to improve adherence to treatment in patients undergoing long-term
      therapy for reflux-related symptoms.

PMID- 25986311
TI  - Association between MutL homolog 1 polymorphisms and the risk of colorectal
      cancer: a meta-analysis.
AB  - PURPOSE: As one of the most essential components of mismatch repair system, MutL
      homolog 1 (MLH1) plays an increasingly implicated role in initiation and
      promotion of colorectal carcinogenesis, with germ-line mutations in different
      loci. However, whether a single genetic variant in MLH1 could predict the risk of
      cancer was still under doubt and recent studies yielded inconsistent results.
      Therefore, this meta-analysis aimed at investigating the association between MLH1
      single-nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) risks.
      METHODS: A systematic literature search of PubMed, MEDLINE, Web of Science and
      BIOSIS databases was performed to obtain all available SNPs and studies. We
      focused on three SNPs (rs1800734, rs1799977 and rs63750448) with the most
      included studies and conducted overall and subgroup analyses after data
      extraction. RESULTS: A total of 37,347, 29,114 and 2722 patients in case and
      control groups were meta-analyzed in four genetic models (AA vs. BB, AB vs. BB,
      AA+AB vs. BB and AA vs. BB+AB) for each SNP. The overall results suggested that
      the mutation in rs63750447 predicted a higher CRC risk (AB vs. BB: OR 2.283, 95 %
      CI 1.612-3.232, P = 0.000; AA+AB vs. BB: OR 2.291, 95 % CI 1.618-3.244, P =
      0.000), while rs1800734 and rs1799977 were not associated with CRC risks.
      Subgroup analysis according to study area, quality score and genotyping technique
      revealed the similar results. CONCLUSIONS: As the first meta-analysis reporting
      the association between rs63750448 and CRC risk, the A allele substitution might
      be a risk factor for CRC. Additionally, there was no persuasive evidence showing
      that SNPs of rs1800734 and rs1799977 were related to CRC susceptibility.

PMID- 25986315
TI  - A Retrospective Review of Reconstructive Options and Outcomes of 202 Cases Large
      Facial Mohs Micrographic Surgical Defects, Based on the Aesthetic Unit Involved.
AB  - BACKGROUND: For optimal treatment of facial defects following Mohs micrographic
      surgery (MMS), the aesthetic unit principles should be applied. Often multiple
      staged procedures and revisions are necessary. OBJECTIVE: To analyze the
      reconstructive options and outcomes for complex facial defects per aesthetic
      unit. METHODS: Data of 202 patients, who underwent a facial reconstruction at the
      department of plastic and reconstructive surgery following MMS, were collected.
      RESULTS: The central facial units were affected in more than 70%, with over 20%
      of the defects involving more than 1 unit. Nasal defects required the longest
      reconstruction time (3-staged forehead flap) and periocular defects the most
      revisional procedures. In more than 50%, additional operations (range, 1-5) were
      needed. In 12%, postoperative complications occurred. CONCLUSION: An overview for
      the reconstructive options of extensive facial skin cancer is presented. Proper
      treatment requires a structured multidisciplinary approach in order to achieve
      excellent tumour control and a satisfactory aesthetic and functional end result.

PMID- 25986316
TI  - Non-melanoma Skin Cancer in Canada Chapter 4: Management of Basal Cell Carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy. Growth of
      BCCs leads to local destruction of neighbouring healthy skin and underlying
      tissue and can result in significant functional and cosmetic morbidity.
      OBJECTIVE: To provide guidance to Canadian health care practitioners regarding
      management of BCCs. METHODS: Literature searches and development of graded
      recommendations were carried out as discussed in the accompanying Introduction.
      RESULTS: Although BCCs rarely metastasize, they can be aggressive and
      disfiguring. This chapter describes the natural history and prognosis of BCCs.
      Risk stratification is based on clinical features, including the site and size of
      the tumour, its histologic subtype (nodular vs sclerosing), and its history of
      recurrence. CONCLUSIONS: Various options should be considered for BCC treatment,
      including cryosurgery, curettage, and topical or photodynamic approaches, as well
      as fixed-margin surgery and Mohs micrographic surgery. Stratification of
      recurrence risk for individual BCCs determines the most appropriate therapeutic
      course.

PMID- 25986318
TI  - Quantifying bond distortions in transient enzyme species by a combination of
      density functional theory calculations and time-resolved infrared difference
      spectroscopy. Implications for the mechanism of dephosphorylation of the
      sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1a).
AB  - The sarcoplasmic Ca(2+)-ATPase (SERCA1a) forms two phosphoenzyme intermediates
      during Ca(2+) pumping. The second intermediate E2P hydrolyzes rapidly, which is
      essential for the rapid removal of Ca(2+) from the cytosol of muscle cells. The
      present work studies whether a weakening of the scissile PO bond in the E2P
      ground state facilitates dephosphorylation. To this end, the experimentally known
      vibrational spectrum of the E2P phosphate group was calculated with density
      functional theory (DFT) using structural models at two levels of structural
      complexity: (i) Models of acetyl phosphate in simple environments and (ii) ~150
      atom models of the catalytic site. It was found that the enzyme environment
      distorts the structure of the phosphate group: one of the terminal PO bonds is
      shorter in the catalytic site indicating weaker interactions than in water.
      However, the bond that bridges phosphate and Asp351 is unaffected. This indicates
      that the scissile PO bond is not weakened by the enzyme environment of E2P. A
      second finding was that the catalytic site of the E2P state in aqueous solution
      appears to adopt a structure as in the crystals with BeF3(-), where the ATPase is
      in a non-reactive conformation. The reactant state of the dephosphorylation
      reaction differs from the E2P ground state: Glu183 faces Asp351 and positions the
      attacking water molecule. This state has a 0.04A longer, and thus weaker,
      bridging PO bond. The reactant state is not detected in our experiments,
      indicating that its energy is at least 1kcal/mol higher than that of the E2P
      ground state. 

PMID- 25986319
TI  - Selective One-Dimensional Total Correlation Spectroscopy Nuclear Magnetic
      Resonance Experiments for a Rapid Identification of Minor Components in the Lipid
      Fraction of Milk and Dairy Products: Toward Spin Chromatography?
AB  - We report a rapid, direct, and unequivocal spin-chromatographic separation and
      identification of minor components in the lipid fraction of milk and common dairy
      products with the use of selective one-dimensional (1D) total correlation
      spectroscopy (TOCSY) nuclear magnetic resonance (NMR) experiments. The method
      allows for the complete backbone spin-coupling network to be elucidated even in
      strongly overlapped regions and in the presence of major components from 4 *
      10(2) to 3 * 10(3) stronger NMR signal intensities. The proposed spin
      chromatography method does not require any derivatization steps for the lipid
      fraction, is selective with excellent resolution, is sensitive with quantitation
      capability, and compares favorably to two-dimensional (2D) TOCSY and gas
      chromatography-mass spectrometry (GC-MS) methods of analysis. The results of the
      present study demonstrated that the 1D TOCSY NMR spin-chromatography method can
      become a procedure of primary interest in food analysis and generally in complex
      mixture analysis. 

PMID- 25986320
TI  - The influence of the ketogenic diet on the elemental and biochemical compositions
      of the hippocampal formation.
AB  - A growing body of evidence demonstrates that dietary therapies, mainly the
      ketogenic diet, may be highly effective in the reduction of epileptic seizures.
      All of them share the common characteristic of restricting carbohydrate intake to
      shift the predominant caloric source of the diet to fat. Catabolism of fats
      results in the production of ketone bodies which become alternate energy
      substrates to glucose. Although many mechanisms by which ketone bodies yield its
      anticonvulsant effect are proposed, the relationships between the brain
      metabolism of the ketone bodies and their neuroprotective and antiepileptogenic
      action still remain to be discerned. In the study, X-ray fluorescence microscopy
      and FTIR microspectroscopy were used to follow ketogenic diet-induced changes in
      the elemental and biochemical compositions of rat hippocampal formation tissue.
      The use of synchrotron sources of X-rays and infrared allowed us to examine
      changes in the accumulation and distribution of selected elements (P, S, K, Ca,
      Fe, Cu, Zn, and Se) and biomolecules (proteins, lipids, ketone bodies, etc.) with
      the micrometer spatial resolution. The comparison of rats fed with the ketogenic
      diet and rats fed with the standard laboratory diet showed changes in the
      hippocampal accumulation of P, K, Ca, and Zn. The relations obtained for Ca
      (increased level in CA3, DG, and its internal area) and Zn (decreased areal
      density in CA3 and DG) were analogous to those that we previously observed for
      rats in the acute phase of pilocarpine-induced seizures. Biochemical analysis of
      tissues taken from ketogenic diet-fed rats demonstrated increased intensity of
      absorption band occurring at 1740 cm(-1), which was probably the result of
      elevated accumulation of ketone bodies. Moreover, higher absolute and relative
      (3012 cm(-1)/2924 cm(-1), 3012 cm(-1)/lipid massif, and 3012 cm(-1)/amide I)
      intensity of the 3012-cm(-1) band resulting from increased unsaturated fatty
      acids content was found after the treatment with the high-fat diet. This article
      is part of a Special Issue entitled "Status Epilepticus".

PMID- 25986321
TI  - Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A
      clinical, electrophysiological, and pathological study.
AB  - BACKGROUND: Fat embolism syndrome (FES) is a rare complication of long-bone
      fractures and joint reconstruction surgery. To the best of our knowledge, we
      describe the clinical, electrophysiological, neuroimaging, and neuropathological
      features of the first case of super-refractory nonconvulsive status epilepticus
      (sr-NCSE) secondary to fat embolism. CLINICAL CASE: An 82-year-old woman was
      transferred to our intensive care unit because of a sudden decrease of
      consciousness level, right hemiparesis, and acute respiratory failure in the
      early postoperative period of knee prosthesis surgery. Brain computed tomography
      (TC) including angio-CT and CT perfusion was normal. An urgent video
      electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave
      at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform
      discharges ceased after the administration of 5mg of intravenous diazepam, and
      background activity constituted by diffuse theta waves was observed without
      clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation
      with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring
      was also started. Despite antiepileptic therapy, epileptiform activity recurred
      after the interruption of profound sedation, and valproate and lacosamide were
      added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small
      scattered foci of acute ischemic infarcts and diffuse petechiae involving the
      basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super
      refractory nonconvulsive status epilepticus remained without control for 2 weeks.
      Finally, the patient died. The clinical autopsy revealed a bilateral lung fat
      embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty
      lesions were also seen in the intestine and pancreas. Scattered microscopic
      cerebral infarcts associated with fat emboli in the capillaries were noticed,
      affecting both supra- and infratentorial structures. In addition, occasional
      focal areas of ischemic injury showing filiform neurons with reactive astrocytic
      gliosis background consistent with acute lesions were observed in CA3.
      CONCLUSIONS: Fat embolism should be considered a potential cause of sr-NCSE. This
      article is part of a Special Issue entitled "Status Epilepticus".

PMID- 25986323
TI  - Highly active and stable oxaloacetate decarboxylase Na+ pump complex for
      structural analysis.
AB  - The oxaloacetate decarboxylase primary Na(+) pump (Oad) produces energy for the
      surviving of some pathogenic bacteria under anaerobic conditions. Oad composes of
      three subunits: Oad-alpha, a biotinylated soluble subunit and catalyzes the
      decarboxylation of oxaloacetate; Oad-beta, a transmembrane subunit and functions
      as a Na(+) pump; and Oad-gamma, a single transmembrane alpha-helical anchor
      subunit and assembles Oad-alpha/beta/gamma complex. The molecular mechanism of
      Oad complex coupling the exothermic decarboxylation to generate the Na(+)
      electrochemical gradient remains unsolved. Our biophysical and biochemical
      studies suggested that the stoichiometry of Oad complex from Vibrio cholerae
      composed of alpha, beta, gamma in 4:2:2 stoichiometry not that of 4:4:4. The high
      resolution structure determination of the Oad complex would reveal the energetic
      transformation mechanism from the catalytical soluble alpha subunit to membrane
      beta subunit. Sufficient amount stable, conformational homogenous and active Oad
      complex with the right stoichiometry is the prerequisite for structural analysis.
      Here we report an easy and reproducible protocol to obtain high quantity and
      quality Oad complex protein for structural analysis. 

PMID- 25986322
TI  - High-yield reactivation of anionic tobacco peroxidase overexpressed in
      Escherichia coli.
AB  - Anionic tobacco peroxidase (TOP) is extremely active in chemiluminescence
      reaction of luminol oxidation without addition of enhancers and more stable than
      horseradish peroxidase under antibody conjugation conditions. In addition,
      recombinant TOP (rTOP) produced in Escherichia coli is known to be a perfect
      direct electron transfer catalyst on electrodes of various origin. These features
      make the task of development of a high-yield reactivation protocol for rTOP
      practically important. Previous attempts to reactivate the enzyme from E. coli
      inclusion bodies were successful, but the reported reactivation yield was only
      14%. In this work, we thoroughly screened the refolding conditions for dilution
      protocol and compared it with gel-filtration chromatography. The impressive
      reactivation yield in the dilution protocol (85%) was achieved for 8 MUg/mL
      solubilized rTOP protein and the refolding medium containing 0.3 mM oxidized
      glutathione, 0.05 mM dithiothreitol, 5 mM CaCl2, 5% glycerol in 50 mM Tris-HCl
      buffer, pH 9.6, with 1 MUM hemin added at the 24th hour of incubation. A
      practically important discovery was a 30-40% increase in the reactivation yield
      upon delayed addition of hemin. The reactivation yield achieved is one of the
      highest reported in the literature on protein refolding by dilution. The final
      yield of purified active non-glycosylated rTOP was ca. 60 mg per L of E. coli
      culture, close to the yield reported before for tomato and tobacco plants
      overexpressing glycosylated TOP (60 mg/kg biomass) and much higher than for the
      previously reported refolding protocol (2.6 mg per L of E. coli culture).

PMID- 25986324
TI  - Serum interleukin-4 (IL-4) production is associated with lower fecal egg count in
      parasite-resistant sheep.
AB  - The objective of this experiment was to determine serum interleukin-4 (IL-4)
      concentration in response to Haemonchus contortus infection in parasite-resistant
      and -susceptible lambs. St. Croix (STC) (resistant) and Suffolk/Hampshire
      crossbred (SX) (susceptible) lambs were either not infected (n=5/breed), given a
      primary inoculation (n=5/breed) or challenged infected with H. contortus
      (n=5/breed). Each inoculum given consisted of 10,000 L3 larvae. Blood was
      collected daily for 14 days and then weekly to day 49. Feces were collected on
      day 0 and weekly until day 49. Challenged STC lambs generated significantly lower
      fecal egg count (FEC) (1520 eggs/g SX vs. <50 eggs/gram STC; P<0.001) and had
      higher PCV (34% vs. 29%; P<0.001). Serum IL-4 concentrations of primary-infected
      STC and challenge-infected SX lambs were greater during early infection (days 0
      7) than mid (days 14-28) and late (days 35-49) infection, but was significantly
      reduced (P<0.001) by day 49. Challenge-infected STC lambs incrementally increased
      serum IL-4 from early to late infection. Change in serum IL-4 concentration
      during early, mid and late infection indicated IL-4 concentration in challenge
      infected STC lambs increased during mid and late infection. These data
      demonstrate that parasite-resistant St. Croix sheep generate a potent Th2
      response, as measured by elevated serum IL-4 concentration, which is associated
      with a marked FEC reduction. 

PMID- 25986325
TI  - Eimeria genomics: Where are we now and where are we going?
AB  - The evolution of sequencing technologies, from Sanger to next generation (NGS)
      and now the emerging third generation, has prompted a radical frameshift moving
      genomics from the specialist to the mainstream. For parasitology, genomics has
      moved fastest for the protozoa with sequence assemblies becoming available for
      multiple genera including Babesia, Cryptosporidium, Eimeria, Giardia, Leishmania,
      Neospora, Plasmodium, Theileria, Toxoplasma and Trypanosoma. Progress has
      commonly been slower for parasites of animals which lack zoonotic potential, but
      the deficit is now being redressed with impact likely in the areas of drug and
      vaccine development, molecular diagnostics and population biology. Genomics
      studies with the apicomplexan Eimeria species clearly illustrate the approaches
      and opportunities available. Specifically, more than ten years after initiation
      of a genome sequencing project a sequence assembly was published for Eimeria
      tenella in 2014, complemented by assemblies for all other Eimeria species which
      infect the chicken and Eimeria falciformis, a parasite of the mouse. Public
      access to these and other coccidian genome assemblies through resources such as
      GeneDB and ToxoDB now promotes comparative analysis, encouraging better use of
      shared resources and enhancing opportunities for development of novel diagnostic
      and control strategies. In the short term genomics resources support development
      of targeted and genome-wide genetic markers such as single nucleotide
      polymorphisms (SNPs), with whole genome re-sequencing becoming viable in the near
      future. Experimental power will develop rapidly as additional species, strains
      and isolates are sampled with particular emphasis on population structure and
      allelic diversity. 

PMID- 25986326
TI  - Occurrence of Babesia species in captive reindeer (Rangifer tarandus) in Germany.
AB  - Two cases of acute babesiosis in captive reindeer (Rangifer tarandus) in two
      German zoos in 2009 and 2012 triggered this study to investigate the occurrence
      and species diversity of Babesia parasites infecting reindeer in different zoos
      and deer parks in Germany. Between June and December 2013, blood samples were
      taken from 123 clinically inapparent reindeer from 16 different facilities.
      Samples were tested for the presence of Babesia species DNA by conventional PCR
      and sequence analysis of part of the 18S rRNA gene. Also, Giemsa-stained smears
      of reindeer blood samples were examined for parasitaemia by light microscopy. The
      overall PCR-prevalence in blood samples was 23.6% (n=29). Comparison of sequenced
      amplicons with GenBank entries possibly revealed up to five different Babesia
      species: B. venatorum (n=19), B. capreoli (n=2) and B. capreoli-like (n=4), B.
      odocoilei-like (n=2) and B. divergens (n=1), while one sample turned out to be a
      Theileria sp. Out of the 16 facilities in the study, 12 housed at least one
      positive animal. In Giemsa-stained blood smears, intra-erythrocytic Babesia
      parasites were detected in samples of three reindeer from three locations. The
      high prevalence of Babesia infections implicates babesiosis to be a relevant
      infectious disease threat for captive reindeer in Germany. Consequently, reindeer
      with clinical signs compatible to those of acute babesiosis should either be
      tested for the presence of Babesia spp. DNA or blood smears should be examined
      for parasitaemia. 

PMID- 25986328
TI  - Thank You for Saving My Patient.

PMID- 25986327
TI  - Effects of third generation P-glycoprotein inhibitors on the sensitivity of drug
      resistant and -susceptible isolates of Haemonchus contortus to anthelmintics in
      vitro.
AB  - P-glycoproteins (P-gps) play an important role in the sensitivity of nematodes to
      anthelmintic drugs. They have been implicated in a number of anthelmintic
      resistances, particularly for macrocyclic lactone drugs. Hence, inhibition of
      nematode P-gps has been suggested as a means of reversing some types of
      anthelmintic resistance. The present study aimed to investigate the ability of
      the most-recently developed group of P-gp inhibitors (the so-called 'third
      generation' of inhibitors) including tariquidar, zosuquidar and elacridar, to
      increase the sensitivity of Haemonchus contortus larvae to various anthelmintics
      (ivermectin, levamisole and thiabendazole) in vitro. We compared these compounds
      to some older P-gp inhibitors (e.g. verapamil and valspodar). Larval migration
      and development assays were used to measure the sensitivity of larvae to
      anthelmintics alone, or in combination with P-gp inhibitors. Significant
      increases in sensitivity to ivermectin were observed with zosuquidar and
      tariquidar in larval migration assays (synergism ratios up to 6-fold). Several of
      the inhibitors increased the sensitivity of both the drug-resistant and 
      susceptible isolates (e.g. tariquidar with ivermectin in migration assays,
      zosuquidar with ivermectin in larval development assays), while others had
      significant effects on the resistant isolate only (e.g. zosuquidar with
      ivermectin in migration assays, verapamil with ivermectin in development assays).
      This suggests that some of the inhibitors interact with P-gps representing
      intrinsic pathways present across nematode populations with quite different drug
      sensitivities, while other inhibitors interact with P-gps of significance only to
      resistant nematodes, and hence most likely representing an acquired resistance
      mechanism. The study highlights the potential of the third generation of P-gp
      inhibitors for increasing the sensitivity of nematodes to anthelmintics. 

PMID- 25986329
TI  - McConnell's Sign Is Not Specific for Pulmonary Embolism: Case Report and Review
      of the Literature.
AB  - BACKGROUND: McConnell's sign (right ventricular [RV] free wall hypokinesis with
      apical sparing on echocardiography) is often described as very specific for the
      diagnosis of pulmonary embolism (PE). We present the case of a patient who,
      despite manifesting a classic McConnell's sign, was not found to have a PE. CASE
      REPORT: A 58-year-old woman presented to the emergency department with a cough,
      dyspnea, and leg swelling. A bedside focused cardiac ultrasound revealed
      hypokinesis of the RV free wall, with apical sparing, in the apical four-chamber
      view. A computed tomography angiogram for PE was negative. Ultrasounds of both
      lower extremities were negative for deep venous thrombosis, and a D-dimer was
      only marginally elevated. The patient was ultimately diagnosed with pulmonary
      hypertension due to chronic obstructive pulmonary disease and systemic lupus
      erythematosus. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency
      physicians should be aware that McConnell's sign is not completely specific for
      acute right heart strain from PE.

PMID- 25986330
TI  - Penetrating Aortic Injury Due to a Projectile From a Lawn Mower.

PMID- 25986331
TI  - Intravenous Sodium Valproate for Acute Pediatric Headache.
AB  - BACKGROUND: Headaches are common in the pediatric population, and increase in
      prevalence with age. The abortive medications currently used have a number of
      potential side effects. Sodium valproate (VPA) has been shown to be effective for
      acute treatment in the adult population, but no data exist in the pediatric
      population. OBJECTIVE: The objective of this study was to evaluate the
      effectiveness of VPA for acute pediatric headache in the emergency department.
      METHODS: This was a retrospective case series of all patients <19 years of age
      treated in the pediatric emergency department (PED) at two tertiary care
      pediatric hospitals and with a final diagnosis of migraine or headache who
      received parenteral VPA. Data collected included patient demographics, pain
      reduction, length of stay, and final disposition. RESULTS: From July 2010 to
      February 2014, there were 16 patients who received VPA for acute headache in the
      PED; 4 were excluded. Eighty-three percent were discharged home. Mean length of
      stay in the PED before VPA was 395 min, and 120 min after VPA administration.
      Patients achieved a 17% mean pain score reduction before VPA and approximately an
      additional 40% mean pain reduction after VPA infusion. CONCLUSIONS: VPA appears
      to be an effective agent for acute pediatric headache in this small series.
      Patients responded well to VPA in a relatively short amount of time. Further
      studies are needed to evaluate its effectiveness in combination with other first
      line medications or as a single agent.

PMID- 25986332
TI  - Interrogating Social Sustainability in the Biofuels Sector in Latin America:
      Tensions Between Global Standards and Local Experiences in Mexico, Brazil, and
      Colombia.
AB  - Across the Americas, biofuels production systems are diverse due to geographic
      conditions, historical patterns of land tenure, different land use patterns,
      government policy frameworks, and relations between the national state and civil
      society, all of which shape the role that biofuels play in individual nations.
      Although many national governments throughout the Americas continue to
      incentivize growth of the biofuels industry, one key challenge for biofuels
      sustainability has been concern about its social impacts. In this article, we
      discuss some of the key social issues and tensions related to the recent
      expansion of biofuels production in Mexico, Colombia, and Brazil. We argue that a
      process of "simplification" of ecological and cultural diversity has aided the
      expansion of the biofuels frontier in these countries, but is also undermining
      their viability. We consider the ability of governments and non-state actors in
      multi-stakeholder initiatives (MSI) to address social and environmental concerns
      that affect rural livelihoods as a result of biofuels expansion. We analyze the
      tensions between global sustainability standards, national level policies for
      biofuels development, and local level impacts and visions of sustainability. We
      find that both government and MSI efforts to address sustainability concerns have
      limited impact, and recommend greater incorporation of local needs and expertise
      to improve governance. 

PMID- 25986333
TI  - In situ characterization of resin-dentin interfaces using conventional vs.
      cryofocused ion-beam milling.
AB  - OBJECTIVE: The introduction of focused ion beam (FIB) milling has facilitated
      preparation of hard tissue samples for transmission electron microscope (TEM).
      However, this technique generates high temperature that may alter or damage
      morphological features in biological tissue. Therefore, the aim of this study was
      to determine the effects of cryogenic cooling on the morphological features of
      dentin interfaces with dental restorative materials in samples prepared by FIB
      for TEM examination. METHODS: After preparation of a cylindrical-shaped cavities
      in extracted, non-carious premolar teeth, the specimens were restored with dental
      adhesive/composite and categorized into two restorative materials groups; (PB) a
      combination of Clearfil Protect Bond (Kuraray Noritake Dental, Japan)/Estelite
      Sigma Quick composite (Tokuyama Dental, Japan), and (SB) Filtek Silorane
      restorative system (3M ESPE, USA). The specimens were subjected to interfacial
      cross-sectioning, followed by observation and area selection using confocal laser
      microscopy. Later, ultrathin sections were prepared using FIB with cryogenic
      cooling (PB-C) and (SB-C), or without cooling (PB-NC) and (SB-NC) that all were
      examined under TEM. RESULTS: Resulting TEM images of the ultra-morphological
      features at the resin-dentin nano-interaction zone were improved when FIB
      preparation was conducted in the cryogenic condition and no sign of artifacts
      were detected. SIGNIFICANCE: Conducting ion beam milling with cryogenic cooling
      was advantageous in minimizing the elevation in specimen temperature. This led to
      preservation of dentin microstructures that revealed additional information about
      substrates that are necessary for advanced characterization of tooth-biomaterial
      interactions.

PMID- 25986334
TI  - Letter to the Editor concerning "The relationship between porosity specific
      surface in human cortical bone is subject specific" by Lerebours C.et al. Bone
      2015; 72:109-117.

PMID- 25986335
TI  - Bone lead (Pb) content at the tibia is associated with thinner distal tibia
      cortices and lower volumetric bone density in postmenopausal women.
AB  - Conflicting evidence suggests that bone lead or blood lead may reduce areal bone
      mineral density (BMD). Little is known about how lead at either compartment
      affects bone structure. This study examined postmenopausal women (N=38, mean age
      76 +/- 8, body mass index (BMI): 26.74 +/- 4.26 kg/m(2)) within the Hamilton
      cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone
      lead at 66% of the non-dominant leg and at the calcaneus using (109)Cadmium X-ray
      fluorescence. Volumetric BMD and structural parameters were obtained from
      peripheral quantitative computed tomography images (200 MUm in-plane resolution,
      2.3 +/- 0.5mm slice thickness) of the same 66% site and of the distal 4% site of
      the tibia length. Blood lead was measured using atomic absorption spectrometry
      and blood-to-bone lead partition coefficients (PBB, log ratio) were computed.
      Multivariable linear regression examined each of bone lead at the 66% tibia,
      calcaneus, blood lead and PBB as related to each of volumetric BMD and structural
      parameters, adjusting for age and BMI, diabetes or antiresorptive therapy.
      Regression coefficients were reported along with 95% confidence intervals. Higher
      amounts of bone lead at the tibia were associated with thinner distal tibia
      cortices (-0.972 (-1.882, -0.061) per 100 MUg Pb/g of bone mineral) and integral
      volumetric BMD (-3.05 (-6.05, -0.05) per MUg Pb/g of bone mineral). A higher PBB
      was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower
      trabecular volumetric BMD (-26.83 (-50.37, -3.29)) and trabecular number (-0.08 (
      0.14, -0.02)), per 100 MUg Pb/g of bone mineral after adjusting for age and BMI,
      and remained significant while accounting for diabetes or use of antiresorptives.
      Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11,
      16.48)) and remained significant after age and antiresorptives-adjustment. Lead
      accumulated in bone can have a mild insult on bone structure; but greater
      partitioning of lead in blood versus bone revealed more dramatic effects on both
      microstructure and volumetric BMD.

PMID- 25986336
TI  - The duration of cardiopulmonary resuscitation in emergency departments after out
      of-hospital cardiac arrest is associated with the outcome: A nationwide
      observational study.
AB  - AIM OF THE STUDY: The appropriate duration of cardiopulmonary resuscitation (CPR)
      for patients who experience out-of-hospital cardiac arrest (OHCA) remains
      unknown. This study aimed to evaluate the duration of CPR in emergency
      departments (EDs) and to determine whether the institutions' median duration of
      CPR was associated with survival-to-discharge rate. METHODS: A cohort of adult
      patients from a nationwide OHCA registry was retrospectively evaluated. The main
      variable was the median duration of CPR for each ED (institutional duration), and
      the main outcome was survival to discharge. Multivariable logistic regression
      analysis was performed to adjust for individual and aggregated confounders.
      RESULTS: Among the 107,736 patients who experienced OHCA between 2006 and 2010,
      30,716 (28.5%) were selected for analysis. The median age was 65 years, and 67.1%
      were men. The median duration of CPR for all EDs was 28 min, ranging from 11 to
      45 min. EDs were categorized into 3 groups according to their institutional
      duration of CPR: groups A (< 20 min), B (20-29 min), C (>= 30 min). The observed
      survival rates of the 3 groups were 2.11%, 5.20%, and 5.62%, respectively.
      Compared with group B, the adjusted difference (95% confidence interval) for
      survival to discharge was 3.01% (1.90-4.11, P<0.001) for group A, and 0.33% (
      0.64 to 1.30, P=0.51) for group C. CONCLUSION: The duration of CPR varied widely
      among hospitals. The institutional duration of CPR less than 20 min was
      significantly associated with lower survival-to-discharge rate.

PMID- 25986337
TI  - Implementation and outcomes of a medical emergency team (MET) e-learning program.

PMID- 25986338
TI  - Small-sized and highly dispersed Pt nanoparticles loading on graphite
      nanoplatelets as an effective catalyst for methanol oxidation.
AB  - A series of high loading Pt nanoparticles (NPs) with a small particle size
      uniformly dispersed on graphite nanoplatelets (GNPs) have been synthesized in the
      presence of an imidazolium-based ionic liquid (Pt/I-IL (x)/GNPs). I-IL, an
      amphoteric ion used as an additive agent to stabilize Pt NPs, can also prevent
      the aggregation of the GNPs. The results obtained from X-ray diffraction,
      transmission electron microscopy and electrochemical testing showed that the I-IL
      assisted synthesis method resulted in size reduction of Pt NPs, an improvement of
      Pt dispersion on GNPs, and the identification of the relationships between the
      mean size of Pt NPs and the volume of I-IL. Among all as-prepared Pt/GNP
      catalysts with or without I-IL assisted, the sample with 10 microliters of I-IL
      assisted (Pt/I-IL (10)/GNPs) exhibits the highest electrocatalytic activity and
      the best stability toward the methanol oxidation reaction. Moreover, the Pt/I-IL
      (10)/GNP catalyst markedly outperforms the commercial Pt/C from Johnson Matthey
      in terms of both methanol oxidation activity and stability, revealed by cyclic
      voltammetry, chronoamperometry and electrochemical impedance spectroscopy. 

PMID- 25986340
TI  - Enabling [(18)F]-bicyclo[6.1.0]nonyne for oligonucleotide conjugation for
      positron emission tomography applications: [(18)F]-anti-microRNA-21 as an
      example.
AB  - A bicyclononyne-based prosthetic group has been developed for (18)F-labeling of
      anti-microRNA-21, an oligonucleotide, in a near-stoichiometric manner. 

PMID- 25986339
TI  - Mutational spectrum and clinical features in 35 unrelated mainland Chinese
      patients with GNE myopathy.
AB  - GNE myopathy is an autosomal recessive distal myopathy caused by biallelic
      mutation in the GNE gene. It shows great genetic heterogeneity among different
      ethnic groups. In this study, we summarized the mutational spectrum and clinical
      profiles in 35 unrelated GNE myopathy patients from mainland China. Molecular
      analysis revealed 16 novel (p.G47D, p.F66Y, p.E173A, p.Y186H, p.R246L, p.R263*,
      p.R306*, p.A366D, p.V512M, p.C520Y, p.G545R, p.G548S, p.V622G, p.A638P, IVS2+1G>A
      and c.2112delC) and 13 reported mutations. Notably, the p.D176V mutation was
      detected in 65.7% (23/35) of this patient cohort, giving an allele frequency of
      34.3% (24/70). We estimated the carrier frequency of p.D176V to be 0.19% (1/520)
      in the normal population, although haplotype analysis indicated no founder effect
      in the patients carrying p.D176V mutation. Clinically, 29 patients presented with
      the classic phenotype of predominant distal weakness, while six patients
      presented with atypical phenotype. However, muscle magnetic resonance imaging
      showed that the vastus lateralis was spared in both subgroups. In conclusion,
      p.D176V mutation in the GNE gene, which was the second most common mutation in
      Japanese patients, was the most common mutation in this cohort of Chinese
      patients. Novel GNE mutations found in this study expanded the mutational
      spectrum associated with GNE myopathy. There is phenotypic heterogeneity among
      patients with GNE myopathy, but muscle magnetic resonance imaging can be useful
      for differential diagnosis.

PMID- 25986341
TI  - Percutaneous ultrasonic debridement of tendinopathy-a pilot Achilles rabbit
      model.
AB  - BACKGROUND: Tendinopathy is a common clinical pathology, with mixed treatment
      results, especially when chronic. In this study, we examine the effects of an
      ultrasonic debridement modality in a rabbit tendinopathy model. We asked four
      questions: (1) Was it possible to create and visualize with ultrasound a
      tendinopathy lesion in a rabbit Achilles tendon? (2) Was it possible to guide a
      19-gauge ultrasonic probe into the tendinopathy lesion? (3) Following ultrasonic
      treatment, was tendinopathy debris histologically present? and (4) Was the
      collagen profile qualitatively and quantitatively normalized following treatment?
      METHODS: Skeletally mature female New Zealand white rabbits (n = 12) were
      injected with, ultrasonography localization, 0.150 ml of collagenase into the
      Achilles tendon. The collagenase-induced Achilles tendinopathy (3 weeks) was
      treated with percutaneous ultrasonic debridement. The tendons were harvested, at
      3 weeks after treatment, and were subjected to histological assessment (modified
      Movin score) and biochemical analysis (collagen isoform content). RESULTS:
      Histopathological examination revealed that all tendons injected with collagenase
      showed areas of hypercellularity and focal areas of tendon disorganization and
      degeneration. The treated tendons had lower (improved) histopathological scores
      than injured tendons (P < 0.001). Western blot analysis showed that ultrasonic
      therapy restored, within statistical limits, collagen type I, III, and X
      expressions in a treated tendon, to qualitative and semi-quantitative levels of a
      normal tendon. CONCLUSIONS: We were successfully able to create a collagenase
      injected tendinopathy lesion in a rabbit Achilles tendon and visualize the lesion
      with an ultrasound probe. A 19-gauge ultrasonic probe was inserted into the
      tendinopathic lesion under direct ultrasound guidance, and minimal tendinopathic
      debris remained after treatment. The treated tendon demonstrated a normalized
      qualitative and semi-quantitative collagen profile and improved histological
      appearance in the short term. This technique demonstrates scientific merit with
      respect to the minimally invasive treatment of tendinopathy and warrants further
      studies. CLINICAL RELEVANCE: Recalcitrant tendinopathy has evaded consistent non
      operative treatment since the tendinopathic debris remains in situ, to some
      extent, with non-operative approaches. This percutaneous
      emulsification/evacuation approach, under direct ultrasound visualization, has
      the potential to cure recalcitrant tendinopathies without open surgery, which
      would benefit the patient and result in significant healthcare cost reductions.

PMID- 25986342
TI  - PLCzeta disruption with complete fertilization failure in normozoospermia.
AB  - PURPOSE: Intracytoplasmic sperm injection (ICSI) is widely used to achieve
      fertilization in the presence of severe male factor, resulting in high
      fertilization rates. Nevertheless, 1-3 % of couples experience complete
      fertilization failure after ICSI. When a male factor is identified, assisted
      oocyte activation (AOA) can help overcome fertilization failures. The objective
      of this study is to describe a case of repeated complete fertilization failures
      after ICSI with donor oocytes, and to investigate the molecular and functional
      aspects of phospholipase C zeta (PLCzeta) protein in the patient semen. METHODS:
      The patient was a normozoospermic male who had previously fathered, through
      natural conception, four children by a different partner. Molecular and
      functional analysis of sperm-specific PLCzeta in the patient and control samples
      by means of gene sequencing, immunocytochemistry, Western blot, mouse oocyte
      activation test (MOAT), and mouse oocyte calcium analysis (MOCA) were used.
      RESULTS: PLCzeta expression levels and distribution were significantly disrupted,
      although MOAT and MOCA did not indicate a decrease in activation ability.
      CONCLUSIONS: Normozoospermic males can have disrupted expression and distribution
      of PLCzeta, and reduced activation ability after ICSI in human oocytes, despite
      their normal activation potential in functional testing using mouse oocytes.
      Discrepancy among molecular and functional data might exist, as mutations in the
      gene sequence may not be the only cause of alteration in PLCzeta protein related
      to activation failures.

PMID- 25986343
TI  - Contained rupture of common iliac artery aneurysm in a contrast-enhanced PET/CT
      study.

PMID- 25986344
TI  - Breast cancer lymphoscintigraphy: Factors associated with sentinel lymph node non
      visualization.
AB  - OBJECTIVE: To evaluate factors associated with non identification of the sentinel
      lymph node (SLN) in lymphoscintigraphy of breast cancer patients and analyze the
      relationship with SLN metastases. MATERIAL AND METHODS: A single-center, cross
      sectional and retrospective study was performed. Forty patients with
      lymphoscintigraphy without sentinel lymph node identification (negative
      lymphoscintigraphy - NL) were enrolled. The control group included 184 patients
      with SLN identification (positive lymphoscintigraphy - PL). Evaluated factors
      were age, body mass index (BMI), tumor size, histology, localization,
      preoperative breast lesion hookwire (harpoon) marking and SLN metastases. The
      statistical analysis was performed with uni- and multivariate logistic regression
      models and matched-pairs analysis. RESULTS: Age (p=0.036) or having BMI (p=0.047)
      were the only factors significantly associated with NL. Being >=60 years with a
      BMI >=30 increased the odds of having a NL 2 and 3.8 times, respectively. Marking
      with hookwire seems to increase the likelihood of NL, but demonstrated
      statistical significance is lacking (p=0.087). The other tested variables did not
      affect the examination result. When controlling for age, BMI and marking with the
      harpoon, a significant association between lymph node metastization and NL was
      not found (p=0.565). CONCLUSIONS: The most important factors related with non
      identification of SLN in the patients were age, BMI and marking with hook wire.
      However, only the first two had statistical importance. When these variables were
      controlled, no association was found between NL and axillary metastases.

PMID- 25986345
TI  - Placing our professions in context.

PMID- 25986347
TI  - Periprosthetic Joint Infection in Patients Receiving TNFalpha Antagonists.
AB  - Tumor necrosis factor-alpha antagonists (anti-TNFalpha) have become increasingly
      more common as a treatment for rheumatoid arthritis (RA). However, there has been
      an increased incidence of severe infections in patients taking anti-TNFalpha
      therapy. We present a case series of RA patients treated with anti-TNFalpha
      therapy that had previously underwent TJA and subsequently developed
      periprosthetic infections. All patients had a well-functioning implant for a
      period of 1 to 14 years prior to the development of infection. Each patient
      underwent two to five different joint replacements, and four patients developed
      infection in multiple sites. The infections proved difficult to eradicate with
      four patients requiring multiple procedures, and one patient ultimately requiring
      a hemipelvectomy. This study suggests that periprosthetic infections acquired by
      patients on anti-TNFalpha therapy are challenging to eradicate and treat;
      highlighting the need for the establishment of guidelines for perioperative and
      long-term management of anti-TNFalpha therapy, and infection monitoring in joint
      replacement patients.

PMID- 25986348
TI  - Partial subscapularis release for total shoulder arthroplasty: a biomechanical
      comparison of two techniques.
AB  - BACKGROUND: Glenohumeral joint exposure during total shoulder arthroplasty (TSA)
      is obtained by releasing the subscapularis (SSC) with either an osteotomy or a
      tenotomy. Recently, concerns regarding SSC dysfunction after TSA have been
      raised. In order to avoid this complication, alternative surgical approaches that
      release the inferior 50% or 10% of the tendon have been described. While a 10%
      release of the SSC would theoretically lower the likelihood of postoperative SSC
      dysfunction, releasing 50% would provide greater surgical exposure but possibly
      have a weaker SS attachment. Therefore, we sought to compare the SSC attachment
      strengths of these two techniques. MATERIALS AND METHODS: Each of eight matched
      pairs of cadaveric shoulders were tested. The inferior 10% of the SSC tendon was
      released on one side. On the contralateral side, the inferior 50% of the SSC was
      released and then repaired with a 5.5 mm suture anchor. The specimens were then
      mechanically tested to failure. RESULTS: The load to failure for the 10% release
      specimens was 682 +/- 153 N and 493 +/- 212 N for the 50% release specimens (p =
      0.036). Failures in both groups occurred mainly at the musculotendonous junction.
      DISCUSSION: The SSC humeral attachment strength after releasing the inferior 10%
      was 30% greater than the 50% re- lease with repair. Thus, although releasing the
      inferior 50% of the SSC tendon may provide greater surgical exposure, maintaining
      the SSC with minimal release may be preferable in decreasing the rate of post TSA
      SSC dysfunction.

PMID- 25986349
TI  - The impact of orthopaedic injuries sustained at an urban public ice skating rink:
      is it really free?
AB  - INTRODUCTION: Previous reports in the literature from Europe and Asia cite an
      increased burden on the local emergency departments and orthopaedic services
      during the operational period of the ice skating rinks. This retrospective
      observational study was undertaken in order to report the incidence,
      characteristic, and severity of injuries during a full season at a large urban
      ice skating rink, as well as to quantify the added burden the ice skating rink
      places on the local emergency department and the orthopaedic service. METHODS:
      All patients seen at our emergency room who sustained an injury at the
      neighboring "free" ice rink were identified over the 4-month period when it was
      open. The data collected included type of injury, demographics, and need for
      surgical treatment. RESULTS: Over this period, 118 patients were seen in our ED
      (of the 135 referrals from the ice rink logbook); Of these, 43 (38%) required an
      orthopaedic consult and were evenly divided into upper (22) and lower extremity
      injuries (21). Sixty-seven percent of the patients were adults, and the most
      common fractures were ankle and distal radius fractures. There were two open
      fractures of the distal radius seen in the older patients (both in patients >
      50). Overall 32% of patients needed operative treatment. Of the non-orthopaedic
      injuries, the most common was head injury (25%). CONCLUSIONS: An ice-rink may be
      "free" but adds significant burden to the healthcare system, and these costs
      should be factored in by both the sponsoring body and the healthcare system for
      treatment of these additional patients.

PMID- 25986346
TI  - Differential expression and clinical significance of three inflammation-related
      microRNAs in gangliogliomas.
AB  - PURPOSE: miR21, miR146, and miR155 represent a trio of microRNAs which has been
      shown to play a key role in the regulation of immune and inflammatory responses.
      In the present study, we investigated the differential expression and clinical
      significance of these three miRNAs in glioneuronal tumors (gangliogliomas, GGs)
      which are characterized by prominent activation of the innate immune response.
      METHODS: The expression levels of miR21, miR146, and miR155 were evaluated using
      Taqman PCR in 34 GGs, including 15 cases with sufficient amount of perilesional
      cortex. Their expression was correlated with the tumor features and the clinical
      history of epilepsy. In addition, in situ hybridization was used to evaluate
      their cellular distribution in both tumor and peritumoral cortex. RESULTS:
      Increased expression of miR146a was observed in both tumor and peritumoral cortex
      compared to control samples. miR146a was detected in both neuronal and astroglial
      cells. Tumor and peritumoral miR146a expression was negatively correlated with
      frequency of seizures and the density of activated microglial cells. Neuronal and
      astroglial expression was observed for both miR21 and miR155 with increased
      expression of miR21 within the tumor and miR155 in the peritumoral region.
      Negative correlations were observed between the miRNA levels and the expression
      of putative targets within the astroglial component of the tumor. CONCLUSION: We
      report a differential regulation of three miRNAs, known to be related to
      inflammation, in both tumor and peritumoral cortex of patients with GG. Moreover,
      our findings suggest a functional relationship between miR146a expression and
      epilepsy, either directly in epileptogenesis or as modulation of seizure
      activity.

PMID- 25986350
TI  - Ultrasound guidance for intra-articular knee and shoulder injections: a review.
AB  - Intra-articular injections have traditionally been performed "blind," guided only
      by anatomic palpation. Many may be placed inaccurately, and the use of imaging
      may significantly improve injection accuracy. This review analyzed the impact of
      ultrasound-guidance on injection accuracy and clinical efficacy in the knee and
      shoulder joints. Ultrasound-guided injections were significantly more accurate
      than blind injections in clinical studies of the knee joint (92.7% vs. 77.9%, p <
      0.05). Shoulder injections into the glenohumeral and acromioclavicular joints
      showed modest benefit in cadaver studies, but improved accuracy has not been
      demonstrated in clinical studies. Insufficient data was available to show any
      effect in the subacromial bursa. Preliminary efficacy research shows that that
      ultrasound guidance may modestly improve the subjective pain relief and
      functional improvement provided by these injections.

PMID- 25986351
TI  - Recognizing conflict of interest in orthopaedic surgery: a survey across medical
      education levels.
AB  - The relationship between pharmaceutical and biomedical technology companies
      (industry) and medical practitioners has been a topic of discussion and concern
      for several decades. The large monetary payments and extravagant gifts to
      physicians from these companies have been regulated and largely stopped; however,
      there still exists an active rapport between physicians and industry. Little
      formal instruction is given to medical students and residents on what constitutes
      a conflict of interest when entering these business partnerships. In this study,
      we presented a set of scenarios depicting industry-physician interactions to
      medical students, orthopaedic surgery residents, and attending physicians and
      asked them to decide whether a conflict of interest is depicted. Our goal was to
      determine whether a disparity exists in the ability to identify conflicts of
      interest across the levels of training. Of 200 potential participants, 70
      provided responses to the survey (35%). Thirty-five (50%) were attending
      physicians, 18 (25.7%) residents, 12 (17.1%) medical students, and 8 (11.4%)
      declined to provide level of training. There was no significant difference in the
      ability to identify a conflict of interest across seniority level for the 13
      questions. Our results suggest that both medical students and resident physicians
      are able to identify which interactions with industry pose a possible conflict of
      interest as accurately as attending physicians can.

PMID- 25986352
TI  - Outcomes of anterior cruciate ligament reconstruction in patients older than 50
      years of age.
AB  - BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) has traditionally
      been reserved for young patients with functional instability. As the aging
      population continues to grow and embrace a more active lifestyle, it is important
      to determine if favorable outcomes of ACLR can be achieved in older adults.
      METHODS: Patients greater than 50 years of age undergoing ACLR between January
      2001 and September 2006 were identified. Charts were retrospectively reviewed for
      clinical, pathologic, and radiographic findings. Prospective data was collected
      at follow-up, including Lysholm Knee Score, Tegner Activity Level Score,
      International Knee Documentation Committee (IKDC) Subjective Knee Form Score, and
      Knee Injury and Osteoarthritis Outcome Score (KOOS). Anteroposterior (AP)
      instability was assessed with use of a KT-2000 arthrometer (MEDmetric, San Diego,
      CA). RESULTS: Forty-seven patients underwent ACLR with 32 (16 males and 16
      females) available at a mean follow-up of 5.0 years (range: 2.2 to 9.0 years).
      The mean age at the time of operation was 58.4 years (range: 51 to 65 years). At
      time of final follow-up, the mean side-to-side difference measured by KT-2000 was
      1.2 +/- 1.3 mm (range: 0 to 4.5 mm). Mean postoperative subjective IKDC score was
      80.1 (range: 33 to 100) and Lysholm score was 86.7 (range: 45 to 95). There was
      no change in Tegner score from pre-injury (range: 0 to 3) to postoperative
      (range: 0 to 3). Twelve patients (38%) underwent subsequent knee surgery. All
      patients were satisfied with the final outcome of their ACLR surgery. Only
      patellofemoral Outerbridge cartilage grade was associated with worse outcome.
      CONCLUSION: ACLR provides symptomatic relief and restoration of function for
      patients greater than 50 years of age. ACLR should be considered in active older
      patients with subjective functional instability.

PMID- 25986353
TI  - Comparison of arthroscopic and MRI findings of osteochondral damage in knees.
AB  - Magnetic resonance imaging (MRI) scans are widely used in the assessment of
      knees, often prior to arthroscopic procedures. The reporting of osteochondral
      damage on MRI scans can be variable. The correlation between MRI reports of
      osteochondral damage and that found at arthroscopy is often inconsistent. A
      retrospective case-note review of a single-surgeon series of 175 arthroscopic
      procedures was performed. Eighty-three patients were included in the study. The
      remainder were excluded if an MRI scan had not been performed or had been
      performed more than 3-months before surgery. The condition of the articular
      cartilage demonstrated by MRI was compared to that found at arthroscopy. Data was
      analysed for presence and extent of osteochondral damage. Comparison between MRI
      and arthroscopy findings showed high specificity (90%) and negative predictive
      values (89%) for osteochondral damage but low sensitivity (46%). Cohen's kappa
      values < 0.2 revealed very poor correlation for the extent of damage. This study
      demonstrates MRI as a good identifier of osteochondral damage but an unreliable
      descriptor for such change.

PMID- 25986354
TI  - Hand stiffness following distal radius fractures: who gets it and is it a
      functional problem?
AB  - PURPOSE: In order to identify predictors for hand stiffness following distal
      radius fractures and understand the consequences of this common clinical finding,
      we studied 260 patients. Our null hypothesis was that we would find no predictors
      of post injury hand stiffness. METHODS: Baseline demographics and injury
      characteristics were obtained at distal radius fracture presentation. Treatment
      and healing was documented. Stiffness was defined as tip to palm distance greater
      than 1 cm for any one finger. Outcome parameters obtained at regular intervals
      included wrist and hand range of motion, radiographs, visual analog pain scales,
      and Disability of the Arm Shoulder and Hand (DASH) questionnaires. RESULTS: Forty
      nine of 260 patients (19%) patients were considered to be "stiff" by our
      criteria. Grip strength was weaker for stiff patients as well. Patient
      demographics were similar in both groups with the "stiff" cohort having a greater
      mean age, p = 0.05. There was no significant difference in stiffness seen in
      operative cases versus nonoperative cases. Injury ulnar variance was 3.1mm (SD =
      3.5) in the "stiff" cohort and 1.8 (SD = 2.9) in the "non-stiff" cohort (p=
      0.02). Functional disability as measured by the DASH differed (p = 0.001) between
      stiff and non-stiff patients for both 6 month and 1 year follow-up time points.
      Stiff patients were more likely than non-stiff patients to have lower grip
      strength at 12-month post fracture (p = 0.001). CONCLUSION: Older patients who
      present with significant ulnar variance at injury are more likely to experience
      hand stiffness at some time during their recovery. The development of hand
      stiffness is associated with poorer functional outcome than those who do not
      develop stiffness.

PMID- 25986355
TI  - A case of systemic lupus erythematosus associated with longitudinal extensive
      transverse myelitis, cerebral neutrophilic vasculitis, and cerebritis.
AB  - Systemic Lupus erythematosus (SLE) is an autoimmune disease with multiple
      clinical presentations and manifestations. Here, we report an intriguing case of
      a 30-year-old female with full-blown SLE, associated with longitudinal extensive
      transverse myelitis (LETM) on Magnetic Resonance Imaging (MRI) manifested by
      lower extremity weakness, neurogenic bladder and bowel, and central nervous
      system (CNS) lupus clinically manifested by changes in mood and behavior as well
      as neutrophilic vasculitis and cerebritis on pathology. LETM is a rare
      complication of SLE; however, what makes this case even more intriguing is that
      it additionally had cerebral lesions consistent with neutrophilic vasculitis and
      cerebritis, and that it may all have started at least 10 years prior with
      nonspecific musculoskeletal manifestations subsequently followed by a rash as
      well as intractable fevers of unknown etiology-much later attributed to her
      lupus. Although she had a most concerning and dramatic presentation, she, so far,
      had responded very well to therapy including pulse dose steroids, plasmapheresis,
      intravenous immunoglobulins (IVIG), cyclophosphamide, and related medications.

PMID- 25986356
TI  - Seronegative anti-GBM Disease with Coexistent ANCA Positivity.
AB  - Anti-glomerular basement membrane disease has been reported to coexist with anti
      neutrophil cytoplasmic antibody (ANCA) positive vasculitis. Seronegative anti-GBM
      disease has been previously described and mostly blamed for the relative
      insensitivity of earlier serologic assays. A 58-year-old male was transferred to
      our facility for acute kidney injury. Prior to his hospital admission, the
      patient had a 2 week history of progressive fatigue, fevers, anorexia, vomiting,
      decreased urine output, sinus congestion, and non-productive cough. His
      creatinine reached 13 mg/dL. P-ANCA was positive, anti GBM antibody was negative
      twice, and urinalysis showed hematuria. Chest x-ray demonstrated diffuse
      opacities, concerning for pulmonary hemorrhage. Renal biopsy showed a severe
      necrotizing and crescentic glomerulonephritis with circumferential crescents.
      There was bright linear glomerular basement membrane staining with IgG consistent
      with anti-GBM disease. Given these findings, the patient was started on oral
      cyclophosphamide (160 mg daily), in addition to pulse dose methylprednisolone. He
      was also initiated on therapeutic plasma exchange. Due to worsening renal
      function, hemodialysis was started. The patient was discharged from the hospital
      and completed a course of treatment with cyclophosphamide and prednisone but
      remains oligo-anuric and hemodialysis dependent at 150 days since presentation.
      This case highlights the importance of tissue diagnosis in situations similar to
      this.

PMID- 25986357
TI  - An atypical presentation of heterotopic ossification following pelvic ring
      injury.
AB  - Disruption of the pelvic ring is associated with great morbidity and mortality.
      The high-energy blunt trauma that often leads to these injuries is also
      responsible for the head, chest, spine, extremity, and genitourinary trauma seen
      concurrently. Urethral and bladder injuries have been reported in up to 25% of
      patients with pelvic fractures and can lead to a plethora of urogenital problems.
      Heterotopic ossification of the penis, presenting as erectile dysfunction, has
      never been described as a complication of pelvic ring injury. We present the
      first case of this type of heterotopic ossification, in a 46-year-old male who
      sustained an anteroposterior compression type II injury with no evidence of
      genitourinary tract damage.

PMID- 25986358
TI  - Unusual cases of elbow locking due to synovial cysts: a report of two cases.
AB  - Sudden and intermittent locking of the elbow joint is a com- mon complaint among
      patients who commonly demonstrate degenerative changes in the elbow. Common
      causes of elbow locking include acute trauma, osteochondritis dessicans, synovial
      chondromatosis, and osteoarthritis. Two cases involving patients with symptoms of
      elbow locking secondary to reasons other than loose bodies within the joint are
      presented: a synovial cyst within the posterior aspect of the elbow, specifically
      within the olecranon fossa causing their painful symptoms of locking. These cases
      present unique features in the diagnostic approaches of elbow locking due to the
      unexpected association with synovial cysts. We believe that these findings can
      shed new light on the pathogenesis of this disease.

PMID- 25986359
TI  - Influence of methane emissions and vehicle efficiency on the climate implications
      of heavy-duty natural gas trucks.
AB  - While natural gas produces lower carbon dioxide emissions than diesel during
      combustion, if enough methane is emitted across the fuel cycle, then switching a
      heavy-duty truck fleet from diesel to natural gas can produce net climate damages
      (more radiative forcing) for decades. Using the Technology Warming Potential
      methodology, we assess the climate implications of a diesel to natural gas switch
      in heavy-duty trucks. We consider spark ignition (SI) and high-pressure direct
      injection (HPDI) natural gas engines and compressed and liquefied natural gas.
      Given uncertainty surrounding several key assumptions and the potential for
      technology to evolve, results are evaluated for a range of inputs for well-to
      pump natural gas loss rates, vehicle efficiency, and pump-to-wheels (in-use)
      methane emissions. Using reference case assumptions reflecting currently
      available data, we find that converting heavy-duty truck fleets leads to damages
      to the climate for several decades: around 70-90 years for the SI cases, and 50
      years for the more efficient HPDI. Our range of results indicates that these fuel
      switches have the potential to produce climate benefits on all time frames, but
      combinations of significant well-to-wheels methane emissions reductions and
      natural gas vehicle efficiency improvements would be required. 

PMID- 25986360
TI  - Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous
      Pancreatic Cysts.
AB  - OBJECTIVES: Better diagnostic tools are needed to differentiate pancreatic cyst
      subtypes. A previous metabolomic study showed cyst fluid glucose as a potential
      marker to differentiate mucinous from non-mucinous pancreatic cysts. This study
      seeks to validate these earlier findings using a standard laboratory glucose
      assay, a glucometer, and a glucose reagent strip. METHODS: Using an IRB-approved
      prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42
      mucinous and 23 non-mucinous) with histological correlation were analyzed.
      RESULTS: Median laboratory glucose, glucometer glucose, and percent reagent strip
      positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all
      comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a
      specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a
      sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip
      glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26).
      CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The
      combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had
      a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).
      CONCLUSIONS: Glucose, whether measured by a laboratory assay, a glucometer, or a
      reagent strip, is significantly lower in mucinous cysts compared with non
      mucinous pancreatic cysts.

PMID- 25986361
TI  - Fecal Microbiota in Pediatric Inflammatory Bowel Disease and Its Relation to
      Inflammation.
AB  - OBJECTIVES: Inflammatory bowel disease (IBD) is considered to result from
      interplay between host and intestinal microbiota. While IBD in adults has shown
      to be associated with marked changes in the intestinal microbiota, there are only
      a few studies in children, and particularly studies focusing on therapeutic
      responses are lacking. Hence, this prospective study addressed the intestinal
      microbiota in pediatric IBD especially related to the level of inflammation.
      METHODS: In total, 68 pediatric patients with IBD and 26 controls provided stool
      and blood samples in a tertiary care hospital and 32 received anti-tumor necrosis
      factor-alpha (anti-TNF-alpha). Blood inflammatory markers and fecal calprotectin
      levels were determined. The intestinal microbiota was characterized by
      phylogenetic microarray and qPCR analysis. RESULTS: The microbiota varied along a
      gradient of increasing intestinal inflammation (indicated by calprotectin
      levels), which was associated with reduced microbial richness, abundance of
      butyrate producers, and relative abundance of Gram-positive bacteria (especially
      Clostridium clusters IV and XIVa). A significant association between microbiota
      composition and inflammation was indicated by a set of bacterial groups
      predicting the calprotectin levels (area under curve (AUC) of 0.85). During the
      induction of anti-TNF-alpha, the microbial diversity and similarity to the
      microbiota of controls increased in the responder group by week 6, but not in the
      non-responders (P<0.01; response related to calprotectin levels). The abundance
      of six groups of bacteria including those related to Eubacterium rectale and
      Bifidobacterium spp. predicted the response to anti-TNF-alpha medication.
      CONCLUSIONS: Intestinal microbiota represents a potential biomarker for
      correlating the level of inflammation and therapeutic responses to be further
      validated.

PMID- 25986363
TI  - Outcomes of stent retriever thrombectomy in basilar artery occlusion: an
      observational study and systematic review.
AB  - BACKGROUND: Basilar artery occlusion (BAO) remains one of the most devastating
      subtypes of stroke with high mortality and poor outcome. Early recanalisation is
      the most powerful predictor of favourable outcome in patients with stroke, and
      may be improved with mechanical thrombectomy using stent retriever devices.
      However, the benefit in functional outcome and safety of stent retrievers are not
      yet well known. The aim of this study was to assess efficacy and safety profiles
      of stent retriever thrombectomy in BAO patients with stroke. METHODS: We analysed
      data retrospectively from our consecutive clinical series and conducted a
      systematic review and meta-analysis of all previous studies of stent retriever
      thrombectomy in BAO patients with stroke between November 2010 and April 2014.
      RESULTS: From March 2010 to March 2013, 22 patients with acute BAO were treated
      with a Solitaire stent retriever in our series. Favourable outcome was
      significantly associated with younger age and distal BAO. The literature search
      identified 15 previous studies involving a total of 312 subjects. In the meta
      analysis, including our series data, the recanalisation rate (Thrombolysis In
      Cerebral Infarction (TICI) score >= 2b) reached 81% (95% CI 73% to 87%). The rate
      of symptomatic intracranial haemorrhage was 4% (95% CI 2% to 8%), favourable
      outcome (modified Rankin Scale (mRS) <= 2 at 3 months) was found in 42% (95% CI
      36% to 48%) and mortality rate was 30% (95% CI 25% to 36%). CONCLUSIONS: Stent
      retriever thrombectomy is a safe treatment modality for patients with stroke
      presenting with BAO. Although the stent retrievers showed a good recanalisation
      rate, there are currently no randomised clinical trials to assess its clinical
      efficacy in comparison with the reference treatment.

PMID- 25986362
TI  - Gene networks, occlusal clocks, and functional patches: new understanding of
      pattern and process in the evolution of the dentition.
AB  - Our understanding of the evolution of the dentition has been transformed by
      advances in the developmental biology, genetics, and functional morphology of
      teeth, as well as the methods available for studying tooth form and function. The
      hierarchical complexity of dental developmental genetics combined with dynamic
      effects of cells and tissues during development allow for substantial, rapid, and
      potentially non-linear evolutionary changes. Studies of selection on tooth
      function in the wild and evolutionary functional comparisons both suggest that
      tooth function and adaptation to diets are the most important factors guiding the
      evolution of teeth, yet selection against random changes that produce
      malocclusions (selectional drift) may be an equally important factor in groups
      with tribosphenic dentitions. These advances are critically reviewed here. 

PMID- 25986364
TI  - Utility of the MOCA as a cognitive predictor for fitness to drive.

PMID- 25986365
TI  - A smaller amygdala is associated with anxiety in Parkinson's disease: a combined
      FreeSurfer-VBM study.
AB  - BACKGROUND: Up to 50% of all patients with Parkinson's disease (PD) suffer from
      anxiety symptoms, a much higher percentage than in the general population. This
      suggests that PD associated pathological alterations partly underlie these
      symptoms, although empirical evidence is limited. METHODS: Here we investigated
      the association between anxiety symptoms measured with the Beck Anxiety Inventory
      (BAI) and hippocampal and amygdalar volume in 110 early-stage patients with PD.
      Measures of anxiety in PD are often obscured by overlap with the somatic
      symptoms. We therefore also used a subscale of the BAI, established by our recent
      factor analysis, that reflects 'psychological' anxiety symptoms and is
      independent of the severity of PD-related motor and autonomic symptoms. We used
      FreeSurfer and voxel-based morphometry for the volumetric analyses. RESULTS: Both
      software packages showed a negative correlation between the 'psychological'
      subscale of the BAI, but not total BAI and volume of the left amygdala,
      independent of the severity of motor symptoms, autonomic dysfunction and
      dopaminergic or anxiolytic medication status. CONCLUSIONS: These results confirm
      studies in non-PD samples showing lower left amygdalar volume in anxious
      patients. The results also indicate that the 'psychological' BAI subscale is a
      better reflection of neural correlates of anxiety in PD. Whether the left
      amygdalar volume decrease constitutes a premorbid trait, a PD-associated
      neurobiological susceptibility to anxiety or arises as a consequence of chronic
      anxiety symptoms remains to be determined by future prospective longitudinal
      studies. Nonetheless, we speculate that the Parkinson pathology is responsible
      for the reduction in amygdalar volume and the concomitant development of anxiety
      symptoms.

PMID- 25986366
TI  - The 'parkinsonian heart': a diagnostic and prognostic tool.

PMID- 25986367
TI  - Editorial: Programmatic Evaluation of HIV Prevention and Treatment in Nigeria.

PMID- 25986368
TI  - Immunological and Virological Outcomes of Patients Switched from LPV/r to ATV/r
      Containing Second- Line Regimens.
AB  - BACKGROUND: Atazanavir/ritonavir (ATV/r) recently became the preferred protease
      inhibitor (PI) for use in Nigeria since it is dosed once daily, which may improve
      treatment adherence and has fewer side effects than lopinavir/ritonavir (LPV/r)-
      the most widely available PI in resource-limited settings. We, therefore, aimed
      to evaluate the immunologic and virologic effects of switching patients to an
      ATV/r-containing regimen. METHODS: In a large antiretroviral treatment programme
      at the Lagos University Teaching Hospital in Nigeria, 400 patients were switched
      to ATV/r-based second-line ART. We conducted a retrospective evaluation of
      immunologic and virologic outcomes following 24 months on the ATV/r regimens.
      RESULTS: Of the 400 patients switched to an ATV/r containing regimen, 255 were
      virologically suppressed on LPV/r prior to switch, 107 were switched due to
      failure on a first-line regimen, 28 were on saquinavir/ritonavir (SQV/r)-based
      regimen, while 10 were unintentionally switched while non-suppressed on a LPV/r
      based regimen. Demonstrable and sustained immunological responses were documented
      as the median (IQR) CD4+ cell count increased steadily from 466 (323) cells/mm3
      at the time of switch to 490 (346) cells/mm3 at 6 months, and 504 (360) cells/mm3
      at 24 months. Of 99 patients evaluated 12 months after ATV/r switch, 2 (2%) had
      detectable viral load (VL). None of the 26 (0%) in this group evaluated at 24
      months had detectable viral load. In a comparison group of 576 patients who were
      maintained on LPV/r-based second line regimens, 359 (62.3%) had undetectable
      viral loads. Of 318 patients with VL data 24 months later, 25 (7.9%) had
      detectable VL. There was no significant difference between the proportion of
      patients maintained on LPV/r (7.9%) and those switched to ATV/r (0%) in the
      development of virologic failure after 24 months of follow-up. CONCLUSION: Among
      patients that were switched to ATV/r-containing regimens, we found improvements
      in immunological responses and no increase in risk of virologic failure.

PMID- 25986369
TI  - Treatment Discontinuation in Adult HIV-Infected Patients on First-Line
      Antiretroviral Therapy in Nigeria.
AB  - BACKGROUND: Retention in care and treatment services is critical to health
      outcomes of individuals diagnosed and living with HIV. We evaluated the incidence
      of and risk factors for treatment discontinuation (TD) in a large adult HIV
      population on ART in Nigeria. METHOD: A retrospective cohort study of adult HIV
      patients initiated on first-line ART between 2004 and 2011 at the Jos University
      Teaching Hospital (JUTH) in Nigeria. Follow up information of participants was
      retrieved from various sources (patient visit database, pharmacy data and
      patients charts) up to the end of 2012. The primary study endpoint was TD,
      defined as discontinuation of ART for any reason, including death or loss to
      follow-up (lack of pharmacy pick-up for periods>=12 months). The Incidence and
      hazard for TD were estimated by Kaplan-Meier and Cox proportional regression
      analysis, respectively. RESULT: Overall, 3,362 (28%) patients discontinued
      treatment during 49,436 person-years (py) of follow-up (incidence rate (IR) 6.8
      TD per 100 py). The hazard of treatment discontinuation decreased with increasing
      age (adjusted hazard ratio (aHR 0.99; 95% CI 0.98-0.99). Other independent risk
      factors for treatment discontinuation were: being unmarried (aHR 1.24; 95% CI:
      1.12-1.38), having primary or secondary level of education as compared to
      tertiary level education (aHR 1.24; 95% CI: 1.12-1.40) and average percent
      adherence to drug refill visits<95% (adjusted hazard ratio (aHR) 2.13; 95% CI:
      1.9-2.40). Compared to tenofovir, greater hazard of TD was noted in patients
      initiated on ART containing didanosine (aHR) 1.73; 95% CI: 1.03-2.91), but lower
      in those initiated on zidovudine containing regimen (aHR 0.77; 95% CI: 0.69
      0.86). CONCLUSION: Long-term treatment discontinuation rate in this study was
      comparable to estimates in resource-rich countries. Younger patients, as well as
      patients with lower educational levels and those with poor adherence had
      significant hazards for treatment discontinuation and should be the target of
      interventions to reduce treatment discontinuation and improve retention,
      especially within the first year of ART.

PMID- 25986370
TI  - Mother-to-Child Transmission Outcomes of HIV-Exposed Infants Followed Up in Jos
      North-Central Nigeria.
AB  - OBJECTIVE: Since 2010, Nigeria has adopted World Health Organization (WHO)
      'Option B' which requires administration of triple antiretroviral prophylaxis or
      treatment (ART) to all HIVinfected pregnant women. We studied the transmission
      outcomes of HIV-exposed children up to 18 months of age. DESIGN: This was a
      retrospective, observational study of HIV-infected pregnant women and their
      exposed infants who accessed prevention of mother to child transmission (PMTCT)
      services at Jos University Teaching Hospital, Jos, North-central Nigeria.
      METHODS: HIV-infected women were enrolled during antenatal care or at
      labor/delivery between January 1, 2010 and December 31, 2012. Antiretroviral
      (ARV) prophylaxis/therapy was provided according to the 2010 Nigerian PMTCT
      guidelines (adapted WHO 2010 guidelines); Infant HIV diagnosis was performed at 6
      weeks and at 6 months. HIV antibody diagnosis was used for exposed children at 18
      months. RESULTS: A total of 996 HIV-exposed children were followed up. Of those
      children, 140 (14.1%) were lost to follow up by 18 months of age. Twelve children
      (1.4%) died (all HIV negative) before 18 months of age and six infants (0.7%)
      were confirmed to be HIV-infected (4 by the age of 6 months and 2 thereafter) and
      were referred for treatment. A total of 838 (84.1%) children tested HIV negative
      at 18 months and were discharged. Mother-to-child transmission (MTCT) of HIV by
      18 months was lower among women on ART before pregnancy compared to those women
      who started ART/Triple ARV prophylaxis during pregnancy/delivery. (0.4%; 3/700 vs
      2.0%; 3/150 P=0.05). Home delivery was associated with higher transmission than
      facility delivery (p=0.03). Mode of delivery or method of infant feeding had no
      significant impact on vertical transmission by 18 months. CONCLUSION: In North
      central Nigeria where HIV is prevalent, ART started before pregnancy is
      enormously effective in preventing mother-to-child transmission. Adoption of WHO
      'Option B+' deserves serious consideration in such settings.

PMID- 25986371
TI  - Loss to Follow-Up within the Prevention of Mother-to-Child Transmission Care
      Cascade in a Large ART Program in Nigeria.
AB  - BACKGROUND: The 2013 WHO guidelines incorporated simplified and more effective
      antiretroviral regimens for the purposes of preventing mother-to-child
      transmission of HIV. With ideal implementation of these recommendations,
      perinatal HIV transmission could be reduced to less than 2%. However, loss to
      follow-up (LTFU) has the potential to erode the success of programs and a number
      of studies report high rates of LTFU within the prevention of mother-to-child
      transmission (PMTCT) care cascade. We evaluated the timing and magnitude of LTFU
      in a large programmatic PMTCT cohort in Nigeria in order to focus future efforts
      to reduce loss in this high burden setting. METHODS: From 2004-2014, the
      APIN/Harvard PEPFAR program supported antenatal HIV screening for nearly one
      million pregnant women and provided PMTCT care to over 30,000 women. The care
      cascade for women enrolling in the PMTCT program includes antenatal, delivery,
      and infant follow-up services through 12-18 months of life. In this retrospective
      cohort analysis, we examined data collected between 2004-2014 from 31 clinical
      sites in Nigeria and assessed the numbers of mothers and infants enrolled and
      LTFU at various points along the care cascade. RESULTS: Among 31,504 women
      (median age 30, IQR: 27-34) entering PMTCT care during the antenatal period,
      20,679 (66%) completed the entire cascade of services including antenatal,
      delivery, and at least one infant follow-up visit. The median gestational age at
      presentation for antenatal care services was 23 weeks (IQR: 17-29). The median
      infant age at last follow-up visit was 12 months (IQR: 5-18). The greatest loss
      in the PMTCT care cascade occurred prior to delivery care (21%), with a further
      16% lost prior to first infant visit. Of the 38,223 women who entered at any
      point along the PMTCT cascade, an HIV DNA PCR was available for 20,202 (53%) of
      their infants. Among infants for whom DNA PCR results were available, the rate of
      HIV transmission for infants whose mothers received any antenatal and/or delivery
      care was 2.8% versus 20.0% if their mother received none. CONCLUSION: In this
      large cohort analysis, the proportion of women LTFU in the PMTCT care cascade was
      lower than that reported in previous cohort analyses. Nevertheless, this
      proportion remains unacceptably high and inhibits the program from maximally
      achieving the goals of PMTCT care. We also provide the largest analysis to date
      on rates of perinatal HIV transmission, with low rates among women receiving
      NNRTI- or PI-based regimens, approaching that reported in clinical trials.
      However, among mothers who received any antenatal care, infant outcomes were
      unknown for 48%, and women presented later in pregnancy than that recommended by
      current guidelines. Implementation research to evaluate ways to improve
      integration of services, particularly transitions from antenatal to delivery and
      pediatric care, are critically needed to reduce LTFU within PMTCT programs and
      achieve the ultimate goal of eliminating pediatric HIV infection.

PMID- 25986372
TI  - Patterns of Adherence and Loss to Follow-Up in Pediatric Patients on ART in
      Nigeria.
AB  - INTRODUCTION: High levels of adherence to antiretroviral therapy (ART) and
      retention in treatment programs are required for successful virologic suppression
      and treatment outcomes. While there have been numerous studies focusing on
      adherence and loss to follow-up (LTFU) in adults, studies in children and young
      adolescents are limited. For this study, we examined patterns of adherence and
      LTFU in HIV-infected pediatric patients receiving ART in PEPFAR-funded sites in
      Nigeria. METHODS: We conducted a retrospective observational study utilizing data
      that had been collected during the course of care in a large pediatric ART
      program in Nigeria. RESULTS: A total of 3,513 children ages 0-14.9 years enrolled
      at 31 different sites between June 2005 and March 2011 were included in the
      study. Of the enrolled patients, 1,987 (56%) were LTFU by the end of the study
      period. LTFU was highest in those ages<2 years and those>=13 years (versus aged 2
      12.9 years). Year of ART initiation was a strong predictor of LTFU across all age
      groups. For those patients retained to 12 months, less than half showed optimal
      adherence (>=95%). While there were no differences in adherence rates at month 12
      by age group, those aged 10 years and older did have declining adherence starting
      at 18 months. DISCUSSION: Adherence is critical for optimal ART patient outcomes.
      We found both low adherence and high LTFU rates in our study cohort. Additional
      studies focused on barriers to adherence and development of age-specific
      intervention programs are critical to improving overall pediatric outcomes.

PMID- 25986373
TI  - The N-Terminal Region of HIV-1 Tat Protein Binds CD127 in Human CD8 T Cells to
      Target the Receptor for Down Regulation Through Tat's Basic Region.
AB  - We have previously shown that soluble HIV-1 Tat protein down regulates surface
      expression of the interleukin (IL)-7 receptor alpha-chain (CD127) on human CD8 T
      cells resulting in impaired T cell proliferation and cytolytic capacity. Once
      taken up by CD8 T cells, Tat translocates to the inner leaflet of the plasma
      membrane where it interacts with the cytoplasmic tail of CD127 inducing receptor
      internalization and degradation by the proteasome. Here we characterized the
      regions of Tat required to interact with CD127 and induce receptor down
      regulation from the cell surface. To do this, a series of histidine-tagged Tat
      deletion mutants were generated and expressed as purified soluble protein, or
      cloned into a DNA expression vector and transfected into primary human CD8 T
      cells and a CD127 expressing Jurkat cell line. Protein-protein interactions were
      assessed by co-immunoprecipitation. Substitution of the first 10 Nterminal
      residues or deletion of residues 17-21 prevented Tat from interacting with and
      down regulating CD127 from the cell surface. Deletion of the basic region also
      prevented Tat from down regulating CD127 but did not prevent Tat from binding to
      the receptor. Notably, an endogenously expressed Tat variant lacking the basic
      region caused an accumulation of CD127 at the cell surface. We propose a model
      where Tat interacts with CD127 via its N-terminal region and recruits cellular
      factors via its basic region to down regulate CD127 from the cell surface. 

PMID- 25986374
TI  - Implementing Implementation Science: An Approach for HIV Prevention, Care and
      Treatment Programs.
AB  - Though great progress has been realized over the last decade in extending HIV
      prevention, care and treatment in some of the least resourced settings of the
      world, a substantial gap remains between what we know works and what we are
      actually achieving in HIV programs. To address this, leaders have called for the
      adoption of an implementation science framework to improve the efficiency and
      effectiveness of HIV programs. Implementation science (IS) is a multidisciplinary
      scientific field that seeks generalizable knowledge about the magnitude of,
      determinants of and strategies to close the gap between evidence and routine
      practice for health in real-world settings. We propose an IS approach that is
      iterative in nature and composed of four major components: 1) Identifying
      Bottlenecks and Gaps, 2) Developing and Implementing Strategies, 3) Measuring
      Effectiveness and Efficiency, and 4) Utilizing Results. With this framework, IS
      initiatives draw from a variety of disciplines including qualitative and
      quantitative methodologies in order to develop new approaches responsive to the
      complexities of real world program delivery. In order to remain useful for the
      changing programmatic landscape, IS research should factor in relevant timeframes
      and engage the multi-sectoral community of stakeholders, including community
      members, health care teams, program managers, researchers and policy makers, to
      facilitate the development of programs, practices and polices that lead to a more
      effective and efficient global AIDS response. The approach presented here is a
      synthesis of approaches and is a useful model to address IS-related questions for
      HIV prevention, care and treatment programs. This approach, however, is not a
      panacea, and we will continue to learn new ways of thinking as we move forward to
      close the implementation gap. 

PMID- 25986375
TI  - Industrial Ecology: The role of manufactured capital in sustainability.

PMID- 25986376
TI  - Entamoeba mitosomes play an important role in encystation by association with
      cholesteryl sulfate synthesis.
AB  - Hydrogenosomes and mitosomes are mitochondrion-related organelles (MROs) that
      have highly reduced and divergent functions in anaerobic/microaerophilic
      eukaryotes. Entamoeba histolytica, a microaerophilic, parasitic amoebozoan
      species, which causes intestinal and extraintestinal amoebiasis in humans,
      possesses mitosomes, the existence and biological functions of which have been a
      longstanding enigma in the evolution of mitochondria. We previously demonstrated
      that sulfate activation, which is not generally compartmentalized to
      mitochondria, is a major function of E. histolytica mitosomes. However, because
      the final metabolites of sulfate activation remain unknown, the overall scheme of
      this metabolism and the role of mitosomes in Entamoeba have not been elucidated.
      In this study we purified and identified cholesteryl sulfate (CS) as a final
      metabolite of sulfate activation. We then identified the gene encoding the
      cholesteryl sulfotransferase responsible for synthesizing CS. Addition of CS to
      culture media increased the number of cysts, the dormant form that differentiates
      from proliferative trophozoites. Conversely, chlorate, a selective inhibitor of
      the first enzyme in the sulfate-activation pathway, inhibited cyst formation in a
      dose-dependent manner. These results indicate that CS plays an important role in
      differentiation, an essential process for the transmission of Entamoeba between
      hosts. Furthermore, we show that Mastigamoeba balamuthi, an anaerobic, free
      living amoebozoan species, which is a close relative of E. histolytica, also has
      the sulfate-activation pathway in MROs but does not possess the capacity for CS
      production. Hence, we propose that a unique function of MROs in Entamoeba
      contributes to its adaptation to its parasitic life cycle. 

PMID- 25986377
TI  - Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces
      cerevisiae.
AB  - Cohesins are required both for the tethering together of sister chromatids
      (termed cohesion) and subsequent condensation into discrete structures-processes
      fundamental for faithful chromosome segregation into daughter cells.
      Differentiating between cohesin roles in cohesion and condensation would provide
      an important advance in studying chromatin metabolism. Pds5 is a cohesin
      associated factor that is essential for both cohesion maintenance and
      condensation. Recent studies revealed that ELG1 deletion suppresses the
      temperature sensitivity of pds5 mutant cells. However, the mechanisms through
      which Elg1 may regulate cohesion and condensation remain unknown. Here, we report
      that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of
      cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the
      DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would
      similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal
      that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion
      defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast,
      RAD61 deletion rescues the condensation defect, but importantly, neither the
      temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In
      combination, these findings reveal that cohesion and condensation are separable
      pathways and regulated in nonredundant mechanisms. These results are discussed in
      terms of a new model through which cohesion and condensation are spatially
      regulated. 

PMID- 25986378
TI  - Advanced glycation end products facilitate bacterial adherence in urinary tract
      infection in diabetic mice.
AB  - Diabetic individuals have increased susceptibility to urinary tract infection
      (UTI), a common, painful condition. During diabetes mellitus, non-enzymatic
      reactions between reducing sugars and protein amine groups result in excessive
      production of advanced glycation end products (AGEs) that accumulate in tissues.
      Since bacteria adhere to cell surfaces by binding to carbohydrates, we
      hypothesized that adherence of bacteria to the bladder in diabetics may be
      enhanced by accumulation of AGEs on urothelial surface proteins. Using a murine
      model of UTI, we observed increased adherence of type 1 fimbriated uropathogenic
      Escherichia coli (UPEC) to the bladder in streptozotocin-induced diabetic female
      mice compared with age-matched controls, along with increased concentrations of
      two common AGEs in superficial urothelial cells from diabetic bladders. Several
      lectins with different specificities exhibited increased binding to urothelial
      homogenates from diabetic mice compared with controls, and two of those lectins
      also bound to AGEs. Furthermore, mannose-binding type 1 fimbriae isolated from
      UPEC bound to different AGEs, and UPEC adherence to the bladder in diabetic mice,
      were inhibited by pretreatment of mice with the AGE inhibitor pyridoxamine. These
      results strongly suggest a role for urothelial AGE accumulation in increased
      bacterial adherence during UTI in diabetes. 

PMID- 25986381
TI  - Erratum to: Clinician's guide to prevention and treatment of osteoporosis.

PMID- 25986380
TI  - Genetic diversity of male and female Chinese bayberry (Myrica rubra) populations
      and identification of sex-associated markers.
AB  - BACKGROUND: Chinese bayberry (Myrica rubra Sieb. & Zucc.) is an important
      subtropical evergreen fruit tree in southern China. Generally dioecious, the
      female plants are cultivated for fruit and have been studied extensively, but
      male plants have received very little attention. Knowledge of males may have a
      major impact on conservation and genetic improvement as well as on breeding.
      Using 84 polymorphic SSRs, we genotyped 213 M. rubra individuals (99 male
      individuals, 113 female varieties and 1 monoecious) and compared the difference
      in genetic diversity between the female and the male populations. RESULTS:
      Neighbour-joining cluster analysis separated M. rubra from three related species,
      and the male from female populations within M. rubra. By structure analysis, 178
      M. rubra accessions were assigned to two subpopulations: Male dominated (98) and
      Female dominated (80). The well-known cultivars 'Biqi' and 'Dongkui', and the
      landraces 'Fenhong' are derived from three different gene pools. Female
      population had a slightly higher values of genetic diversity parameters (such as
      number of alleles and heterozygosity) than the male population, but not
      significantly different. The SSR loci ZJU062 and ZJU130 showed an empirical Fst
      value of 0.455 and 0.333, respectively, which are significantly above the 95 %
      confidence level, indicating that they are outlier loci related to sex
      separation. CONCLUSION: The male and female populations of Chinese bayberry have
      similar genetic diversity in terms of average number of alleles and level of
      heterozygosity, but were clearly separated by genetic structure analysis due to
      two markers associated with sex type, ZJU062 and ZJU130. Zhejiang Province China
      could be the centre of diversity of M. rubra in China, with wide genetic
      diversity coverage; and the two representative cultivars 'Biqi' and 'Dongkui',
      and one landrace 'Fenhong' in three female subpopulations. This research provides
      genetic information on male and female Chinese bayberry and will act as a
      reference for breeding programs.

PMID- 25986382
TI  - Epidemiology of fragility fractures in Sakaiminato, Japan: incidence, secular
      trends, and prognosis.
AB  - We investigated the incidence of fragility fractures from 2010 to 2012 in
      Sakaiminato, Japan. The incidence rates of limb fractures in Sakaiminato were
      lower than in Caucasian populations but had increased relative to data obtained
      in Japan in the 1990s. Clinical vertebral fractures occurred at higher rates in
      Sakaiminato than in Caucasian populations. INTRODUCTION: To elucidate the
      incidence and prognosis of fragility fractures in Sakaiminato, Japan. METHODS: A
      survey of all hip, distal radius, proximal humerus, and clinical vertebral
      fractures was performed from 2010 to 2012 in patients aged 50 or older in
      Sakaiminato city, Tottori prefecture, Japan. The age- and gender-specific
      incidence rates (per 100,000 person-years) were calculated based on the
      population of Sakaiminato city each year. The incidence rates of hip, distal
      radius, and proximal humerus fractures were compared with previous reports. We
      conducted a follow-up study assessing patients within 1 year following their
      initial treatment at two Sakaiminato hospitals. RESULTS: The age-adjusted
      incidence rates in population aged 50 years or older (per 100,000 person-years)
      of hip, distal radius, proximal humerus, and clinical vertebral fractures were,
      respectively, 217, 82, 26, and 412 in males and 567, 432, 96, and 1229 in
      females. Age-specific incidence rates of hip, distal radius, and proximal humerus
      fractures all increased since the 1990s. Our study also revealed that anti
      osteoporotic pharmacotherapy was prescribed 1 year post-fracture at rates of 29,
      20, 30, and 50 % for patients with hip, distal radius, proximal humerus, and
      clinical vertebral fractures, respectively. CONCLUSIONS: The incidence rates of
      limb fractures in Sakaiminato were substantially lower than Caucasian populations
      in northern Europe but had increased relative to data obtained in Japan in the
      1990s. Unlike upper and lower limb fractures, clinical vertebral fractures
      occurred at higher rates in our study population than in other Asian and North
      European countries.

PMID- 25986383
TI  - Marrow adiposity assessed on transiliac crest biopsy samples correlates with
      noninvasive measurement of marrow adiposity by proton magnetic resonance
      spectroscopy ((1)H-MRS) at the spine but not the femur.
AB  - Measurement of marrow fat (MF) is important to the study of bone fragility. We
      measured MF on iliac biopsies and by spine/hip magnetic resonance spectroscopy in
      the same subjects. Noninvasively assessed spine MF and histomorphometrically
      assessed MF correlated well. MF quantity and relationships with bone volume
      differed by measurement site. INTRODUCTION: Excess marrow fat has been implicated
      in the pathogenesis of osteoporosis in several populations. In the bone marrow,
      adipocytes and osteoblasts share a common precursor and are reciprocally
      regulated. In addition, adipocytes may secrete toxic fatty acids and adipokines
      that adversely affect osteoblasts. Measurement of marrow fat is important to the
      study of mechanisms of bone fragility. Marrow fat can be quantified on bone
      biopsy samples by histomorphometry and noninvasively by proton magnetic resonance
      spectroscopy ((1)H-MRS). In this study, we evaluate relationships between marrow
      fat assessed using both methods in the same subjects for the first time. METHODS:
      Sixteen premenopausal women, nine with idiopathic osteoporosis and seven normal
      controls, had marrow fat measured at the iliac crest by bone biopsy and at the
      lumbar spine (L3) and proximal femur by (1)H-MRS. RESULTS: At L3, fat fraction by
      (1)H-MRS correlated directly and significantly with marrow fat variables on iliac
      crest biopsies (r = 0.5-0.8). In contrast, there were no significant correlations
      between fat fraction at the femur and marrow fat on biopsies. Marrow fat quantity
      (%) was greater at the femur than at L3 and the iliac crest and correlated
      inversely with total hip and femoral neck BMD by DXA. CONCLUSIONS: In summary,
      measurement of marrow fat in transiliac crest biopsies correlates with marrow fat
      at the spine but not the proximal femur by (1)H-MRS. There were site-specific
      differences in marrow fat quantity and in the relationships between marrow fat
      and bone volume.

PMID- 25986385
TI  - Use of proton pump inhibitors is associated with fractures in young adults: a
      population-based study.
AB  - Proton pump inhibitors (PPIs) are associated with risk for fracture in
      osteoporotic adults. In this population-based study, we found a significant
      association between PPIs and fracture in young adults, with evidence of a dose
      response effect. Young adults who use PPIs should be cautioned regarding risk for
      fracture. INTRODUCTION: Proton pump inhibitors (PPIs) are associated with
      fracture in adults with osteoporosis. Because PPI therapy may interfere with bone
      accrual and attainment of peak bone mineral density, we studied the association
      between use of PPIs and fracture in children and young adults. METHODS: We
      conducted a population-based, case-control study nested within records from
      general medical practices from 1994 to 2013. Participants were 4-29 years old
      with >= 1 year of follow-up who lacked chronic conditions associated with use of
      long-term acid suppression. Cases of fracture were defined as the first incident
      fracture at any site. Using incidence density sampling, cases were matched with
      up to five controls by age, sex, medical practice, and start of follow-up. PPI
      exposure was defined as 180 or more cumulative doses of PPIs. Conditional
      logistic regression was used to estimate the odds ratio and confidence interval
      for use of PPIs and fracture. RESULTS: We identified 124,799 cases and 605,643
      controls. The adjusted odds ratio for the risk of fracture associated with PPI
      exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and
      1.39 (95% CI 1.26 to 1.53) among young adults aged 18-29 years old. In young
      adults but not children, we observed a dose-response effect with increased total
      exposure to PPIs (p for trend <0.001). CONCLUSIONS: PPI use was associated with
      fracture in young adults, but overall evidence did not support a PPI-fracture
      relationship in children. Young adults who use PPIs should be cautioned regarding
      potentially increased risk for fracture, even if they lack traditional fracture
      risk factors.

PMID- 25986384
TI  - Orthogeriatrics in the management of frail older patients with a fragility
      fracture.
AB  - This review article examines the role of orthogeriatric management for frail
      older patients with a fragility fracture. The history of orthogeriatrics and its
      application in clinical practice around the world is reported, and an evidence
      based evaluation for the effect of orthogeriatric management on patient morbidity
      and mortality is also provided. It has been more than 50 years since the role of
      the geriatrician in the management of patients with a hip fracture was first
      described. The evidence that supports an orthogeriatric model of care has grown
      exponentially over the last decade. This evidence base is primarily related to
      hip fractures and demonstrates reduced morbidity and mortality rates amongst
      patients managed with a recognised model of orthogeriatric care. The societal and
      economic burden of hip fracture has led to health economic evaluations within
      this field, many of which have concluded that orthogeriatric management results
      in cost-effective clinical practice. Based on existing clinical and economic
      research, national clinical practice guidelines have been developed in several
      countries which recommend orthogeriatric participation in the management of older
      patients with a hip fracture. Compliance with such guidance has already
      demonstrated improved patient outcomes. Although the pathogenesis and prognosis
      of other types of fragility fracture may be as poor, there is a dearth of
      clinical research that evaluates the effect of orthogeriatric management on such
      injuries. Looking to the future, orthogeriatric management is likely to become
      more widespread, and the robust collection and reporting of patient outcomes from
      national registries will provide a greater understanding of the impact of
      orthogeriatric models in the care of all frail older patients with any type of
      fragility fracture.

PMID- 25986386
TI  - The burden of osteoporotic hip fractures in Portugal: costs, health related
      quality of life and mortality.
AB  - The study rationale was to provide a detailed overview of the costs, quality of
      life and mortality of hip fractures in Portugal. Mean individual fracture-related
      costs were estimated at ?13,434 [12,290; 14,576] for the first year and ?5985
      [4982; 7045] for the second year following the fracture. INTRODUCTION:
      Osteoporotic fractures represent a remarkable burden to health care systems and
      societies worldwide, which will tend to increase as life expectancy expands and
      lifestyle changes favour osteoporosis. The cost-effectiveness evaluation of
      intervention strategies demands accurate data on the epidemiological and
      economical reality to be addressed. METHODS: Information was collected
      retrospectively on consumption of resources and changes in quality of life
      attributable to fracture as well as mortality, regarding 186 patients randomly
      selected to represent the distribution of hip fractures in the Portuguese
      population, in terms of gender, age and geographical provenience. Data were cross
      tabulated with socio-demographic variables and individual resource consumption to
      estimate the burden of disease. A societal perspective was adopted, including
      direct and indirect costs. Multivariate analyses were carried out to assess the
      main determinants of health-related quality of life (HrQoL). RESULTS: Mean
      individual fracture-related costs were estimated at ?13,434 [12,290; 14,576] for
      the first year and ?5985 [4982; 7045] for the second year following the fracture.
      In 2011 the economic burden attributable to osteoporotic hip fractures in
      Portugal could be estimated at ?216 million. Mean reduction in HrQoL 12 months
      after fracture was estimated at 0.34. Regression analysis showed that age was
      associated with a higher loss of HrQoL, whereas education had the opposing
      effect. We observed 12 % excess mortality in the first year after hip fracture,
      when compared to the gender and age-matched general population. CONCLUSIONS:
      Results of this study indicate that osteoporotic hip fractures are, also in
      Portugal, despite its low incidence of fractures and cost per event, associated
      with a high societal burden, in terms of costs, loss in HrQoL and mortality.
      These data provide valuable input to the design and selection of fracture
      prevention strategies.

PMID- 25986387
TI  - Sleep duration and timing in relation to osteoporosis in an elderly Chinese
      population: a cross-sectional analysis in the Dongfeng-Tongji cohort study.
AB  - This population-based cross-sectional study in an older Chinese population shows
      a link between sleep duration, sleep timing, and osteoporosis risk, suggesting
      that sleep may have a role in osteoporosis development. These findings may help
      to identify contributing mechanisms and provide new opportunities for sleep
      focused interventions to prevent osteoporosis. INTRODUCTION: Accumulated evidence
      suggests that sleep pattern disruption may lead to alterations in physiology,
      potentially triggering the development of osteoporosis. The present study sought
      to examine whether sleep duration or sleep timing is associated with
      osteoporosis. METHODS: A total of 31,769 participants (aged 45-86 years) were
      recruited from the Dongfeng-Tongji cohort study. All participants completed
      questionnaires and medical examinations and provided blood samples. The presence
      of osteoporosis was determined using calcaneal quantitative ultrasonography.
      Logistic regression models were used to evaluate the association of sleep
      duration and timing with osteoporosis, after adjusting for potential confounders.
      RESULTS: The prevalence of osteoporosis was 14.2 % in men and 23.9 % in women.
      After controlling for potential confounders, the adjusted odds ratio (OR) [95 %
      confidence interval (CI)] for osteoporosis comparing sleep duration of 9 h or
      longer with the reference (7-8 h) was 1.40 (1.22-1.62) in men and 1.20 (1.07
      1.33) in women. Men with early sleep timing (going to sleep before 21:00 h) were
      more likely to have osteoporosis (OR, 1.43; 95 % CI, 1.16-1.78) than those with
      normal sleep timing (going to sleep between 21:00 and 23:00 h). In the
      interaction analysis, participants with long sleep duration and early sleep
      timing had the highest risk of osteoporosis both in men (OR, 1.79; 95 % CI, 1.48
      2.16) and women (OR, 1.41; 95 % CI, 1.19-1.66). CONCLUSIONS: Long sleep duration
      (>=9 h) and early sleep timing were independently and interactively associated
      with an increased risk of osteoporosis in this older Chinese population.

PMID- 25986388
TI  - Charge Transfer Plasmons: Optical Frequency Conductances and Tunable Infrared
      Resonances.
AB  - A charge transfer plasmon (CTP) appears when an optical-frequency conductive
      pathway between two metallic nanoparticles is established, enabling the transfer
      of charge between nanoparticles when the plasmon is excited. Here we investigate
      the properties of the CTP in a nanowire-bridged dimer geometry. Varying the
      junction geometry controls its conductance, which modifies the resonance energies
      and scattering intensities of the CTP while also altering the other plasmon modes
      of the nanostructure. Reducing the junction conductance shifts this resonance to
      substantially lower energies in the near- and mid-infrared regions of the
      spectrum. The CTP offers both a high-information probe of optical frequency
      conductances in nanoscale junctions and a new, unique approach to controllably
      engineering tunable plasmon modes at infrared wavelengths. 

PMID- 25986389
TI  - Management of CKD-MBD in non-dialysis patients under regular nephrology care: a
      prospective multicenter study.
AB  - BACKGROUND: Knowledge about mineral bone disorder (MBD) management in non
      dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential
      to identifying areas for therapeutic improvement. METHODS: We prospectively
      evaluated current management of CKD-MBD in two visits, performed 6 months apart,
      in 727 prevalent ND-CKD stage 3b-5 patients from 19 nephrology clinics.
      Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia
      and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the
      prevalence of achieved target for CKD-MBD parameters and related treatments
      (phosphate binders, vitamin D and calcium supplements). The secondary endpoint
      was the assessment of prevalence and clinical correlates of therapeutic inertia.
      RESULTS: Over 65 % of patients did not reach parathormone (PTH) targets, while 15
      and 19 % did not reach phosphate and calcium targets, respectively. The
      proportion of untreated patients decreased from stage 3b to 5 (at baseline, from
      60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of
      targets remained stable. Low protein diet was prescribed in 26 % of patients,
      phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8
      %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the
      6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage
      3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5,
      respectively. CONCLUSIONS: PTH, calcium and phosphate targets were not reached in
      a significant proportion of patients. One-third of patients with at least one MBD
      parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD
      treatment may be a major barrier to optimizing the prevention and cure of CKD
      MBD.

PMID- 25986391
TI  - Spectroscopic evidence for selenium(IV) dimerization in aqueous solution.
AB  - The aqueous speciation of selenium(iv) was elucidated by a combined approach
      applying quantum chemical calculations, infrared (IR), Raman, and (77)Se NMR
      spectroscopy. The dimerization of hydrogen selenite (HSeO3(-)) was confirmed at
      concentrations above 10 mmol L(-1) by both IR and NMR spectroscopy. Quantum
      chemical calculations provided the assignment of vibrational bands observed to
      specific molecular modes of the (HSeO3)2(2-) ion. The results presented will
      provide a better understanding of the chemistry of aqueous Se(iv) which is of
      particular interest for processes occurring at mineral/water interfaces. 

PMID- 25986390
TI  - Rituximab for treatment of severe renal disease in ANCA associated vasculitis.
AB  - BACKGROUND: Rituximab (RTX) is approved for remission induction in ANCA
      associated vasculitis (AAV). However, data on use of RTX in patients with severe
      renal disease is lacking. METHODS: We conducted a retrospective multi-center
      study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with
      and without use of concomitant cyclophosphamide (CYC) for remission induction in
      patients presenting with e GFR less than 20 ml/min/1.73 m(2). We evaluated
      outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at
      diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.
      RESULTS: A total 37 patients met the inclusion criteria. The median age was 61
      years. (55-73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA
      positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m(2) (7-16) and
      15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %)
      received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %)
      received plasma exchange. The median (IQR) follow up was 973 (200-1656) days.
      Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients
      (67 %) requiring dialysis recovered renal function. The median prednisone dose at
      6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22)
      ml/min/m(2). Twelve patients developed ESRD during follow up. There were 3 deaths
      in the first 6 months. When stratified by use of concomitant CYC, there were no
      differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or
      median follow up days between the groups. No differences in remission, renal
      recovery ESRD or death were observed. CONCLUSIONS: This study of AAV patients
      with severe renal disease demonstrates that the outcomes appear equivalent when
      treated with RTX and GC with or without concomitant CYC.

PMID- 25986392
TI  - Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression
      through secretion of interleukin-8.
AB  - BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) have been identified to
      be closely associated with tumor growth and progression. However, the roles of
      tumor-resident MSCs in cancer have not been thoroughly clarified. This study was
      to investigate the regulating effect of gastric cancer-derived MSCs (GC-MSCs) on
      gastric cancer and elucidate the underlying mechanism. METHODS: GC-MSCs were
      isolated from primary human gastric cancer tissues and characterized. The effect
      of GC-MSCs on gastric cancer cell proliferation was analyzed by MTT assay and
      colony formation assay. Transwell migration assay was performed to evaluate the
      influence of GC-MSCs in gastric cancer cell migration. The regulating effects of
      interactions between gastric cancer cells and GC-MSCs on their pro-angiogenic
      abilities were analyzed in a co-culture system, with the expression, and
      secretion of pro-angiogenic factors detected by RT-PCR and Luminex assay. Tube
      formation assay was used to further validate the angiogenic capability of gastric
      cancer cells or GC-MSCs. Cytokine profiles in the supernatant of GC-MSCs were
      screened by Luminex assay and neutralizing antibody was used to identify the key
      effective cytokines. The activations of Akt and Erk1/2 in gastric caner cells
      were detected by Western blot. RESULTS: GC-MSC treatment enhanced the
      proliferation and migration of BGC-823 and MKN-28 cells, which was more potently
      than MSCs from adjacent non-cancerous tissues (GCN-MSCs) or bone marrow (BM
      MSCs). Higher expression levels of pro-angiogenic factors were detected in GC
      MSCs than GCN-MSCs or BM-MSCs. After 10 % GC-MSC-CM treatment, BGC-823, and MKN
      28 cells expressed increased levels of pro-angiogenic factors and facilitated
      tube formation more potently than cancer cells alone. Furthermore, GC-MSCs
      produced an extremely higher level of interleukin-8 (IL-8) than GCN-MSCs or BM
      MSCs. Blockade of IL-8 by neutralizing antibody significantly attenuated the
      tumor-promoting effect of GC-MSCs. In addition, 10 % CM of IL-8-secreted GC-MSCs
      induced the activations of Akt or Erk1/2 pathway in BGC-823 and MKN-28 cells.
      CONCLUSION: Tumor-resident GC-MSCs promote gastric cancer growth and progression
      more efficiently than GCN-MSCs or BM-MSCs through a considerable secretion of IL
      8, which could be a possible target for gastric cancer therapy.

PMID- 25986393
TI  - First-Time Mothers Psychiatric Health Status During the Transition to Motherhood.
AB  - The study was conducted to examine the changes of first-time mothers' psychiatric
      health status, social support, marital intimacy, postpartum stress, and maternal
      attachment during the transition to motherhood. A repeated measures study was
      conducted at the 36th week pregnancy, the first week postpartum, and the fourth
      week postpartum with 217 primiparous women. The results showed that the
      proportion of women with minor psychiatric morbidity declined over time from late
      pregnancy to early postpartum. The levels of marital intimacy and social support
      was the highest at the fourth week and the first week postpartum, respectively.
      Maternal attachment increased and postpartum stress decreased from the first week
      to fourth week postpartum. Women with minor psychiatric morbidity reported
      significantly higher postpartum stress than women without minor psychiatric
      morbidity. Identifying women with psychiatric morbidity in advance, and providing
      social support during late pregnancy would be effective strategies to enhance
      first-time mothers' adjustment to the transition of motherhood.

PMID- 25986394
TI  - DNA methylation similarities in genes of black South Africans with systemic lupus
      erythematosus and systemic sclerosis.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are
      systemic autoimmune connective tissue diseases that share overlapping clinico
      pathological features. It is highly probable that there is an overlap in
      epigenetic landscapes of both diseases. This study aimed to identify similarities
      in DNA methylation changes in genes involved in SLE and SSc. Global DNA
      methylation and twelve genes selected on the basis of their involvement in
      inflammation, autoimmunity and/or fibrosis were analyzed using PCR arrays in
      three groups, each of 30 Black South Africans with SLE and SSc, plus 40 healthy
      control subjects. RESULTS: Global methylation in both diseases was significantly
      lower (<25 %) than in healthy subjects (>30 %, p = 0.0000001). In comparison to
      healthy controls, a similar gene-specific methylation pattern was observed in
      both SLE and SSc. Three genes, namely; PRF1, ITGAL and FOXP3 were consistently
      hypermethylated while CDKN2A and CD70 were hypomethylated in both diseases. The
      other genes (SOCS1, CTGF, THY1, CXCR4, MT1-G, FLI1, and DNMT1) were generally
      hypomethylated in SLE whereas they were neither hyper- nor hypo-methylated in
      SSc. CONCLUSIONS: SSc and SLE patients have a higher global hypomethylation than
      healthy subjects with specific genes being hypomethylated and others
      hypermethylated. The majority of genes studied were hypomethylated in SLE
      compared to SSc. In addition to the commonly known hypomethylated genes in SLE
      and SSc, there are other hypomethylated genes (such as MT-1G and THY-1) that have
      not previously been investigated in SLE and SSc though are known to be
      hypermethylated in cancer.

PMID- 25986395
TI  - Concomitant septic arthritis and osteomyelitis of the hip in young children; a
      new pathophysiological hypothesis suggested by MRI enhancement pattern.
AB  - BACKGROUND: In children, septic arthritis (SA) of the hip is either primary or
      concomitant with acute haematogenous osteomyelitis (AHO). However, seldom,
      patients with isolated SA at presentation, may later show osteomyelitis in the
      metaphysis. The aim of this study was to elaborate a physiopathological
      hypothesis based on the peculiar MRI findings to explain the onset of AHO after
      SA. METHODS: Cases of acute infection of the hip admitted between January 2010
      and December 2013 were retrospectively reviewed to assess radiographic and MRI
      features, as well as bacteriological findings. Only children with isolated SA
      were included in this study, whereas cases of concomitant SA and AHO at
      presentation were excluded. RESULTS: Ten patients met the inclusion criteria. Six
      (1-11 months) demonstrated, on the initial MRI, decreased perfusion on gadolinium
      enhanced fat-suppressed T1-weighted sequence of the femoral epiphysis and
      developed one month later metaphyseal AHO. Four (5-14 years) did not show
      decreased perfusion and did not develop AHO on follow-up. The type of germ
      involved influenced neither the type of enhancement pattern nor the outcome.
      CONCLUSIONS: Age under one year and decreased perfusion of the affected femoral
      epiphysis increases the risk of secondary AHO. Our study is the first report in
      human medicine supporting the physiopathological hypothesis described by Alderson
      et al. in an animal model: primary infection can originally affect the joint,
      then penetrate the epiphyseal cartilage, and finally spread into the metaphyseal
      region through transphyseal vessels present only in the first 12/18 months of
      life.

PMID- 25986396
TI  - Evaluation of axillary involvement by ultrasound-guided lymph node biopsy: A
      prospective study.
AB  - OBJECTIVES: The primary aim of this prospective study was to evaluate the
      accuracy of pre-operative ultrasound (US) alone and associated with a fine needle
      aspiration cytology (FNAC) or a core needle biopsy (CNB) in the diagnosis of
      axillary node involvement in patient with breast cancer. The secondary study
      objective was to determine if this US+/-FNAC or CNB can lead to the adequate
      axillary surgery in cN0 and cN1 patient. METHODS: A total of 121 consecutive
      women with stage cT1 to cT2, cN0/cN1, invasive breast cancer were prospectively
      identified at our institution between February 2, 2013 and August 30, 2013. The
      sensitivity, specificity, VPP, NPV were calculated, with confidence intervals,
      using the definitive histological result of the sentinel node biopsy (SLNB) or
      axillary lymph node dissection (ALND) as the baseline. RESULTS: Twenty-seven CNB
      and 2 FNAC were performed. For the whole series, the sensitivity and the
      specificity of US alone were 48.7% [36-59%] and 89% [83-94%]. For US+/-FNAC or
      CNB, the sensitivity and the specificity were 35.9% [26-38%] and 98.8% [94-100%].
      Seven women with cN1 clinical examination had SLNB, which permit to decrease the
      number of ALND of 16.3%. It would have avoided unnecessary SLNB, prompting
      immediate ALND in 9 patients with cN0 axillae, which means a reduction of SLNB of
      8.6%. US+/-FNAC or CNB lead to the adequate surgery in 72.7% of cases.
      CONCLUSION: US+/-CNB or FNAC is also a relatively efficient and safe test and
      should be considered routinely. It allowed triaging patients to the well axillary
      surgery (SLNB or ALND).

PMID- 25986397
TI  - [Surgery alone or in association with preoperative uterovaginal brachytherapy for
      stage IB1 cervical cancer: Toxicities profiles].
AB  - OBJECTIVE: To assess toxicity profile in two stage-IB1 cervical cancer treatment
      strategies: surgery with and without preoperative uterovaginal pulsed dose-rate
      brachytherapy. METHODS: A retrospective study included 45 patients presenting
      stage-IB1 cervical cancer without pelvic lymph-node invasion, between 2009 and
      2011: 25 treated by colpohysterectomy alone (group A) and 20 with preoperative
      uterovaginal pulsed dose-rate brachytherapy (group B). The median follow-up was
      45 and 39 months (group A and B). RESULTS: Groups were comparable for age
      (median, 46.9 vs 47.6 years), histologic type (52% vs 65% squamous cell
      carcinoma) and tumor size (68% vs 60%, <2cm). In postoperative year 1, rates of
      urinary, digestive and gynaecological disorder were 39.1%, 8.7% and 15%
      respectively in group A versus 36.8%, 5.3% and 31.6% in group B and in year 2,
      5.9%, 8.4% and 15% versus 5.6%, 5.1% and 27.8%. DISCUSSION AND CONCLUSION: The
      present study comparing two stage-IB1 cervical cancer treatment strategies found
      no significant difference in early or late complications. In 2 months, there was
      greater grade-3 urinary toxicity (21.1%) and sexual disorder (15.8%) with
      preoperative brachytherapy but no significant difference. Exclusive surgery is
      probably preferable for the patient's quality of life.

PMID- 25986398
TI  - [The focused ultrasound scan, everything but low-cost].

PMID- 25986399
TI  - [Is vaginal delivery possible for patients with myomectomy? Results of a
      monocentric study].
AB  - OBJECTIVE: To compare delivery outcomes according to the scar: myomectomy versus
      low-segment transverse cesarean. METHODS: A retrospective cohort study was
      performed in a university type 3 service between 1st January 2006 and 1st January
      2012. We compared 18 women who gave birth after myomectomy (exposed group) to 72
      women who gave birth after cesarean section (non-exposed group). Women younger
      than 43 years who underwent laparotomy or laparoscopic myomectomy were included.
      The primary endpoint was the rate of vaginal delivery. The route of delivery, the
      rate of uterine rupture, complications of delivery and neonatal outcome were
      studied. RESULTS: The acceptance rate of vaginal delivery was 55.6% after
      myomectomies versus 84.7% after cesarean section (P=0.005). The success of
      vaginal birth was 88.9% after myomectomy versus 73.9% after cesarean (NS). No
      uterine rupture has occurred after myomectomy against three sub-peritoneal
      rupture after cesarean. The occurrence of post-partum hemorrhage was not
      significantly different between the 2 groups (11.1% among exposed group versus
      6.9% in the non-exposed group). The cesarean section rate was even higher than
      the number of hysterotomy was great (P=0.0047). CONCLUSION: This study seems to
      show that vaginal birth after myomectomy is possible with a success rate similar
      to vaginal birth after cesarean section.

PMID- 25986400
TI  - [Sentinel lymph node-multicentric and multifocal tumors: a valid technique?].
AB  - Sentinel node biopsy without complementary axillary lymph node dissection was
      validated for T1-2 N0 unifocal breast cancer without previous treatment since
      several years. In the situation of multifocal multicentric breast tumors, this
      procedure was considered as a contraindication. The aim of this work was to
      analyse literature results to determine if sentinel lymph node biopsy can be
      considered as a valid option without complementary axillary lymph node dissection
      for negative sentinel lymph node. 

PMID- 25986401
TI  - Height, weight, body composition, and waist circumference references for 7- to 17
      year-old children from rural Portugal.
AB  - The purpose of this study was (1) to develop references of height, weight, body
      mass index (BMI), waist circumference and body fat for rural Portuguese children
      and adolescents and (2) to compare these results with other international
      references. The sample comprised 3094 children and adolescents aged 7-17 years
      from Vouzela, a central region in Portugal. Height, weight, BMI, waist
      circumference and body fat were measured. Centile curves were constructed using
      the LMS method. The Vouzela sample showed similar height median values compared
      to Centers for Disease Control and Prevention (CDC) and World Health Organization
      (WHO) percentile curves but greater values for weight and BMI. Percent body fat
      50th percentile was greater in Vouzela children and adolescents compared to their
      international peers, except for boys aged 8-12 years. Boys' waist circumference
      median values were similar to those from the USA, whilst girls were similar until
      12 years of age, after which the differences increased with age. The percentile
      curves constructed provide population specific references for growth and body
      composition of children and adolescents from rural Portugal. It is expected that
      they will be a useful tool for clinical and public health settings in rural
      Portugal. 

PMID- 25986402
TI  - Progression of behavioural despair in R6/2 and Hdh knock-in mouse models
      recapitulates depression in Huntington's disease.
AB  - In Huntington's disease (HD) depression is observed before the disease is
      diagnosed, and is likely to be a component of the disease, rather than a
      consequence. Depression in HD patients does not progress in parallel with other
      symptoms; rather it peaks at early- to mid-stages of the disease and declines
      thereafter. In mice, depressive-like behaviours can be measured as an increase in
      behavioural despair (floating) observed in the forced swim test (FST). Floating
      in the FST is modulated differently by antidepressants with different mechanisms
      of action. Drugs that increase levels of serotonin inhibit floating by promoting
      horizontal swimming, whereas drugs that increase levels of noradrenaline inhibit
      floating by enhancing vertical swimming (climbing). We compared the FST
      behavioural profiles of two different allelic series of HD mice, a fragment model
      (R6/2 mice carrying 120, 250, or 350 CAG repeats), and a knock-in model (Hdh mice
      carrying 50, 150, or 250 CAG repeats). The FST behavioural profile was similar in
      both lines. It was characterized by an early-stage increase in floating, and
      then, as the mice aged, floating decreased, whereas active behaviours of swimming
      and climbing increased. Our results show that, as with depression in HD patients,
      floating in HD mice does not progress linearly, suggesting that, at the late
      stages of the disease, an increase in serotonergic and noradrenergic activity
      might contribute to lower floating levels in HD mice. If similar compensatory
      changes occur in humans, this should be taken into account when considering the
      treatment of depression in HD patients. 

PMID- 25986403
TI  - Acute restraint stress and corticosterone transiently disrupts novelty preference
      in an object recognition task.
AB  - The object recognition task is a procedure based on rodents' natural tendency to
      explore novel objects which is frequently used for memory testing. However, in
      some instances novelty preference is replaced by familiarity preference, raising
      questions regarding the validity of novelty preference as a pure recognition
      memory index. Acute stress- and corticosterone administration-induced novel
      object preference disruption has been frequently interpreted as memory
      impairment; however, it is still not clear whether such effect can be actually
      attributed to either mnemonic disruption or altered novelty seeking. Seventy-five
      adult male Wistar rats were trained in an object recognition task and subjected
      to either acute stress or corticosterone administration to evaluate the effect of
      stress or corticosterone on an object recognition task. Acute stress was induced
      by restraining movement for 1 or 4h, ending 30 min before the sample trial.
      Corticosterone was injected intraperitoneally 10 min before the test trial which
      was performed either 1 or 24h after the sample trial. Four-hour, but not 1-h,
      stress induced familiar object preference during the test trial performed 1h
      after the sample trial; however, acute stress had no effects on the test when
      performed 24h after sample trial. Systemic administration of corticosterone
      before the test trial performed either 1 or 24h after the sample trial also
      resulted in familiar object preference. However, neither acute stress nor
      corticosterone induced changes in locomotor behaviour. Taken together, such
      results suggested that acute stress probably does not induce memory retrieval
      impairment but, instead, induces an emotional arousing state which motivates
      novelty avoidance.

PMID- 25986404
TI  - Opposite roles for neuropeptide S in the nucleus accumbens and bed nucleus of the
      stria terminalis in learned helplessness rats.
AB  - The role of neuropeptide S (NPS) in depression remains unclear. We examined the
      antidepressant-like effects of NPS infusions into the shell or core regions of
      the nucleus accumbens (NAc) and into the bed nucleus of the stria terminalis
      (BNST) of learned helplessness (LH) rats (an animal model of depression).
      Infusions of NPS (10 pmol/side) into the NAc shell, but not the NAc core and
      BNST, exerted antidepressant-like effects in the LH paradigm. Implying that
      behavioral deficits could be improved in the conditioned avoidance test.
      Coinfusion of SHA68 (an NPS receptor antagonist, 100 pmol/side) with NPS into the
      NAc shell blocked these effects. In contrast, NPS receptor antagonism by SHA68 in
      the BNST induced antidepressant-like effects. Infusions of NPS into the NAc shell
      or SHA68 into the BNST did not produce memory deficits or locomotor activation in
      the passive avoidance and open field tests. These results suggest that excitatory
      and inhibitory actions by the NPS system are integral to the depression in LH
      animals.

PMID- 25986405
TI  - The role of rat posterior parietal cortex in coordinating spatial representations
      during place avoidance in dissociated reference frames on a continuously rotating
      arena (Carousel).
AB  - On the Carousel maze, rats are trained to avoid a sector of a circular rotating
      arena, punishable by a mild electric foot-shock. In the room frame (RF) variant,
      the punishable sector remains stable relative to the room, while in the arena
      frame (AF) version, the sector rotates with the arena. The rats therefore need to
      disregard local olfactory, tactile and self-motion cues in RF condition and
      distal extra-maze landmarks in the AF task. In both primates and rodents, the
      coordination of various spatial reference frames is thought to depend on the
      posterior parietal cortex (PPC). We have previously shown that PPC-lesioned rats
      can solve both variants of the Carousel avoidance task. Here we aimed to
      determine the effects of bilateral thermocoagulation lesion of the PPC in Long
      Evans rats on the ability to transition between multiple spatial strategies. The
      rats were first trained in five sessions in one condition and then another five
      sessions in the other. The following training schemes were used: RF to AF, RF to
      RF reversal (sector on the opposite side), and AF to RF. We found a PPC lesion
      associated impairment in the transition from the AF to RF task, but not vice
      versa. Furthermore, PPC lesion impaired performance in RF reversal. In accordance
      to the literature, we also found an impairment in navigation guided by intra-maze
      visuospatial cues, but not by extra-maze cues in the water maze. Therefore, the
      PPC lesion-induced impairment is neither specific to distant cues nor to
      allocentric processing. Our results thus indicate a role of the PPC in the
      flexibility in spatial behaviors guided by visual orientation cues. 

PMID- 25986406
TI  - A sensitive and reliable test instrument to assess swimming in rats with spinal
      cord injury.
AB  - For clinical translation of experimental spinal cord injury (SCI) research,
      evaluation of animal SCI models should include several sensorimotor functions.
      Validated and reliable assessment tools should be applicable to a wide range of
      injury severity. The BBB scale is the most widely used test instrument, but
      similar to most others it is used to assess open field ambulation. We have
      developed an assessment tool for swimming in rats with SCI, with high
      discriminative power and sensitivity to functional recovery after mild and severe
      injuries, without need for advanced test equipment. We studied various parameters
      of swimming in four groups of rats with thoracic SCI of different severity and a
      control group, for 8 weeks after surgery. Six parameters were combined in a
      multiple item scale, the Karolinska Institutet Swim Assessment Tool (KSAT). KSAT
      scores for all SCI groups showed consistent functional improvement after injury,
      and significant differences between the five experimental groups. The internal
      consistency, the inter-rater and the test-retest reliability were very high. The
      KSAT score was highly correlated to the cross-section area of white matter spared
      at the injury epicenter. Importantly, even after 8 weeks of recovery the KSAT
      score reliably discriminated normal animals from those inflicted by the mildest
      injury, and also displayed the recovery of the most severely injured rats. We
      conclude that this swim scale is an efficient and reliable tool to assess motor
      activity during swimming, and an important addition to the methods available for
      evaluating rat models of SCI. 

PMID- 25986407
TI  - Editorial.

PMID- 25986409
TI  - [Do not harm anybody].

PMID- 25986408
TI  - [Pediatric emergence agitation].
AB  - BACKGROUND: The origin of emergence agitation in children remains unclear;
      however, an association between surgical procedure, patient age and anesthetic
      regimen and the incidence of postoperative agitation has been described in the
      literature. AIM: The aim of this survey performed between February and April 2014
      was to collect data from the daily clinical practice by experienced pediatric
      anesthesiologists regarding documentation, premedication, anesthesia regimen and
      postoperative treatment with respect to children with emergence agitation.
      MATERIAL AND METHODS: An online questionnaire with 33 items was developed and
      sent to all 525 members of the scientific committee of pediatric anesthesia
      (WAKKA) of the German Society of Anesthesiology and Intensive Care (DGAI).
      Members were asked to respond within a time period of 1 month but no reminders
      were sent out via email or telephone. RESULTS: A total of 156 members
      participated in the survey and of these 143 questionnaires were fully completed
      and included in the final evaluation (27 %). Of the participants 77 % had more
      than 6 years professional experience in the field of pediatric anesthesia and for
      87 % emergence agitation remains a relevant clinical problem. The estimated
      incidence of emergence agitation was given as 1-10 % and as high as 11-20 % by
      56% and 20 % of the participants, respectively. The incidence of postoperative
      agitation is documented by only 11 % of the participants with a validated score,
      such as the pediatric anesthesia emergence delirium (PEAD) scale and 89 % of the
      participants use midazolam for premedication. As a preemptive intervention total
      intravenous anesthesia is performed by 56 % whereas clonidine is used as first
      line prevention by 30 %. Postoperative pharmacological treatment is performed by
      a bolus administration of propofol (56 %) and clonidine (26 %). Postoperative
      parental presence was considered beneficial by 82 %. CONCLUSION: Emergence
      agitation is still seen as a relevant clinical problem by experienced pediatric
      anesthesiologists. Propofol is first choice when it comes to pharmacological
      prevention and treatment of emergence agitation. Postoperative parental presence
      was considered beneficial by the majority of anesthesiologists.

PMID- 25986410
TI  - Influence of bovine serum albumin and fetal bovine serum supplementation during
      in vitro maturation on lipid and mitochondrial behaviour in oocytes and lipid
      accumulation in bovine embryos.
AB  - Proper oocyte maturation is crucial for subsequent embryo development; however,
      oocyte mitochondrial and lipid-droplet behaviour are still poorly understood.
      Although excessive lipid accumulation during in vitro production (IVP) of bovine
      embryos has been linked with impaired cryotolerance, lipid oxidation is essential
      for adequate energy supply. Fetal bovine serum (FBS) and bovine serum albumin
      (BSA) are supplements used during IVP, containing high and low lipid content,
      respectively. This study aimed to understand how these supplements influence
      oocyte mitochondrial and lipid behaviour during in vitro maturation (IVM) in
      comparison to in vivo maturation, as well as their influence on development rates
      and embryo lipid accumulation during IVP. We demonstrate that only in vivo
      matured oocytes maintained correlation between lipid content and active
      mitochondria. IVM media containing FBS increased total lipid content 18-fold and
      resulted in higher lipid accumulation in oocytes when compared with media with
      BSA. IVM using a lower FBS concentration combined with BSA resulted in
      satisfactory maturation and embryo development and also reduced lipid
      accumulation in blastocysts. In conclusion, IVM causes changes in mitochondrial
      and lipid dynamics, which may have negative effects on oocyte development rates
      and embryo lipid accumulation. Moreover, decreasing FBS concentrations during IVM
      may reduce embryo lipid accumulation without affecting production rates.

PMID- 25986412
TI  - [Pure word deafness due to epilepsy].

PMID- 25986413
TI  - [The Barres test and Mingazzini test -Importance of the original paper by
      Giovanni Mingazzini].
AB  - In order to find a subtle hemiparesis of the arms and legs, so called "Barre's
      test" has been routinely used in clinical practice. This eponym has been
      questioned by several neurologists. To clarify this, I searched and found the
      original paper by Giovanni Mingazzini, reported in Revue Neurologique in 1913. He
      showed arm drift test with his original photo, as asking the patient to stretch
      his arms in front, hands in the same horizontal plane with the manner of swearing
      and the fingers spread. The eyes are closed. The examiner observes downward drift
      of the hand after one half to a minute. He described a similar test for the legs
      in this article. The patient in supine position raises the legs in a 45 degree
      angle from the bed. If the leg drops downward too early, an organic hemiparesis
      could be present. Barre described a new leg drift test in 1919 with a patient
      lying on the abdomen. He also presented the Mingazzini's arm and leg tests with
      photos as carried by his patient-models in his article of 1937. He did not quote
      the original article of Mingazzini as a reference. These brought us incorrect
      information to consider the presence of Barre's arm test. 

PMID- 25986414
TI  - [Pure word deafness due to a localization-related seizure: a case study].

PMID- 25986415
TI  - Normative adolescent experiences may confound assessment of positive symptoms in
      youth at ultra-high risk for psychosis.

PMID- 25986411
TI  - Multiple regulatory mechanisms in the chloroplast of green algae: relation to
      hydrogen production.
AB  - A complex regulatory network in the chloroplast of green algae provides an
      efficient tool for maintenance of energy and redox balance in the cell under
      aerobic and anaerobic conditions. In this review, we discuss the structural and
      functional organizations of electron transport pathways in the chloroplast, and
      regulation of photosynthesis in the green microalga Chlamydomonas reinhardtii.
      The focus is on the regulatory mechanisms induced in response to nutrient
      deficiency stress and anoxia and especially on the role of a hydrogenase-mediated
      reaction in adaptation to highly reducing conditions and ATP deficiency in the
      cell.

PMID- 25986416
TI  - Greater number of older siblings is associated with decreased theory of mind
      ability in psychosis.

PMID- 25986417
TI  - Perineal reconstruction in the UK: An internet survey.

PMID- 25986418
TI  - PET-CT imaging in patients with chronic sternal wound infections prior to
      reconstructive surgery: A case series.
AB  - Late presenting and recurrent sternal wound infections post-sternotomy are
      difficult to treat, with the clinical picture not necessarily reflecting the
      underlying problem. As a result of our experience, we suggest that these chronic
      cases should be managed using a different algorithm to acute sternal wound
      infection. Positron emission tomography combined with computerized tomography
      (PET-CT) imaging may be potentially useful in enabling accurate localization of
      disease sites, which guides adequate debridement prior to definitive
      reconstruction. It may also allow for disease surveillance and monitoring of the
      response to antimicrobial treatment. We present three cases which support the
      need for pre-operative imaging using PET-CT. 

PMID- 25986419
TI  - Optimizing shape and projection in low-volume bilateral microvascular breast
      reconstruction: Technical tips.

PMID- 25986420
TI  - Online resources for lymphoedema.

PMID- 25986421
TI  - Translating Human Effective Jejunal Intestinal Permeability to Surface-Dependent
      Intrinsic Permeability: a Pragmatic Method for a More Mechanistic Prediction of
      Regional Oral Drug Absorption.
AB  - Regional intestinal effective permeability (P(eff)) values are key for the
      understanding of drug absorption along the whole length of the human
      gastrointestinal (GI) tract. The distal regions of the GI tract (i.e. ileum,
      ascending-transverse colon) represent the main sites for GI absorption when there
      is incomplete absorption in the upper GI tract, e.g. for modified release
      formulations. In this work, a new and pragmatic method for the estimation of
      (passive) intestinal permeability in the different intestinal regions is being
      proposed, by translating the observed differences in the available mucosal
      surface area along the human GI tract into corrections of the historical
      determined jejunal P(eff) values. These new intestinal P(eff) values or
      "intrinsic" P(eff)(P(eff,int)) were subsequently employed for the prediction of
      the ileal absorption clearance (CL(abs,ileum)) for a set of structurally diverse
      compounds. Additionally, the method was combined with a semi-mechanistic
      absorption PBPK model for the prediction of the fraction absorbed (f(abs)). The
      results showed that P(eff,int) can successfully be employed for the prediction of
      the ileal CL(abs) and the f(abs). P(eff,int) also showed to be a robust predictor
      of the f(abs) when the colonic absorption was allowed in the PBPK model, reducing
      the overprediction of f(abs) observed for lowly permeable compounds when using
      the historical P(eff) values. Due to its simplicity, this approach provides a
      useful alternative for the bottom-up prediction of GI drug absorption, especially
      when the distal GI tract plays a crucial role for a drug's GI absorption.

PMID- 25986422
TI  - The Role of Megalin in the Transport of Gentamicin Across BeWo Cells, an In Vitro
      Model of the Human Placenta.
AB  - Aminoglycosides (AG) are known to readily cross the placenta, although the
      mechanisms responsible for placental transport have not been characterized.
      Megalin is expressed in human placenta, and it is reasonable to speculate, given
      its role in renal AG uptake, that it is similarly involved in placental
      transport. However, the role of megalin in placental AG uptake has not been
      established. An in vitro model to study megalin-mediated placental transport has
      also not been previously described. The objectives of this study, therefore, were
      to evaluate the human choriocarcinoma (BeWo) cell line as a model to study
      megalin-mediated placental transport and to assess the uptake kinetics of
      gentamicin, an AG antibiotic, using this in vitro model. BeWo cells were grown on
      Transwell(r) plates, and megalin expression and functional activity were
      assessed. Uptake of (3)H-gentamicin was also evaluated in the presence and
      absence of megalin inhibitors. Expression of megalin protein and mRNA in BeWo
      cells were confirmed via immunoblot and qPCR analysis. Uptake of fluorescein
      isothiocyanate (FITC)-labeled bovine serum albumin (BSA) (a megalin substrate)
      was time-, concentration-, and temperature-dependent consistent with a
      transporter-mediated process. FITC-BSA uptake was also significantly reduced in
      the presence of unlabeled gentamicin (a megalin substrate) and sodium maleate (to
      induce megalin shedding) suggesting that megalin is functionally active in BeWo
      cells. Gentamicin uptake exhibited time and temperature dependence, saturability
      and Michaelis-Menten kinetics, all of which suggest a transporter-mediated
      process. Gentamicin uptake was also significantly reduced in the presence of the
      megalin inhibitors RAP and EDTA suggesting that megalin is likely involved in
      gentamicin uptake. 

PMID- 25986423
TI  - Hypertension: Microanatomy impacts on RDN.

PMID- 25986424
TI  - Transplantation: Outcomes of prenatal immunosuppression.

PMID- 25986425
TI  - Single Incision Laparoscopic Sleeve Gastrectomy: a Review.
AB  - We aim to summarize the existing evidence on the use of single incision sleeve
      gastrectomy (SILSG) for morbid obesity. A thorough literature search for studies
      reporting outcomes of SILSG was performed. Data on patient demographics,
      operative details, and surgical outcomes were analyzed. Sixteen studies
      incorporating 945 patients (90.6 % women) with a mean age of 37 years were
      included in the analysis. A commercially available single-port device was used in
      89.7 % of the cases. The mean operative time was 64.7 min, with two cases (0.2 %)
      of intraoperative and 27 cases (2.8 %) of postoperative complications. There were
      no perioperative deaths reported, while the mean postoperative hospital stay was
      2.5 days. SILSG is a feasible and safe approach, with low complication and
      mortality rates in carefully selected patients.

PMID- 25986426
TI  - Increasing the Value of Healthcare: Improving Mortality While Reducing Cost in
      Bariatric Surgery.
AB  - BACKGROUND: Healthcare costs in the United States (U.S.) are rising. As outcomes
      improve, such as decreased length of stay and decreased mortality, it is expected
      that costs should go down. The aim of this study is to analyze hospital charges,
      cost of care, and mortality in bariatric surgery over time. METHODS: A
      retrospective analysis of the Nationwide Inpatient Sample (NIS) database was
      performed. Adults with morbid obesity who underwent gastric bypass or sleeve
      gastrectomy were identified by ICD-9 codes. Multivariate analyses identified
      independent predictors of changes in hospital charges and in-hospital mortality.
      Results were adjusted for age, race, gender, Charlson comorbidity index, surgical
      approach (open versus laparoscopic), hospital volume, and insurance status. In
      order to estimate baseline surgical inflation, changes in hospital charges over
      time were also calculated for appendectomy. RESULTS: From 1998 to 2011, 209,106
      patients were identified who underwent bariatric surgery. Adjusted in-hospital
      mortality for bariatric surgery decreased significantly by 2003 compared to 1998
      (p < 0.001, OR 0.47, 95 % CI 0.22-0.92) and remained significantly decreased for
      the remainder of the study period. As such, a 60-80 % decrease in mortality was
      maintained from 2003 to 2010 compared to 1998. After adjusting for inflation, the
      cumulative increase in hospital charges per day of a bariatric surgery admission
      was 130 % from 1998 to 2011. Charges per stay increased by 2.1 % annually for
      bariatric surgery compared to 5.5 % for appendectomy. CONCLUSION: In-hospital
      mortality rate following bariatric surgery underwent a ninefold decrease since
      1998 while maintaining surgical inflation costs less than appendectomy.
      Innovation in bariatric surgical technique and technology has resulted in
      improvement of outcomes while providing overall cost savings.

PMID- 25986427
TI  - Effects of Fat and Protein Preloads on Pouch Emptying, Intestinal Transit,
      Glycaemia, Gut Hormones, Glucose Absorption, Blood Pressure and Gastrointestinal
      Symptoms After Roux-en-Y Gastric Bypass.
AB  - BACKGROUND: The aim was to determine the effects of fat and protein preloads on
      pouch emptying (PE), caecal arrival time (CAT), glucose absorption, blood glucose
      (BSL), gut hormones, haemodynamics and gastrointestinal (GI) symptoms in subjects
      who had undergone Roux-en-Y gastric bypass (RYGB) >12 months previously. METHODS:
      Ten RYGB subjects were studied on three occasions, in randomised order, receiving
      200-ml preloads of either water, fat (30 ml olive oil) or whey protein (55 g), 30
      min before a mixed meal. PE, CAT, BSL, plasma 3-O-methyl-D-glucopyranose (3-OMG),
      insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like
      peptide 1 (GLP-1) and glucagon, blood pressure (BP), heart rate (HR) and GI
      symptoms were assessed over 270 min. RESULTS: Although fat and protein preloads
      did not alter PE of either solids or liquids, the CAT of solids, but not liquids,
      was longer than that after the water preload (fat 68 +/- 5 min and protein 71 +/-
      6 min vs. water 46 +/- 5 min; P = 0.02). BSL elevated promptly after the meal on
      all days (P < 0.001), but after protein, the magnitude and integrated increases
      in the first 75 min were less than fat and water preloads (area under the curve
      (AUC(0-75 min)), 18.7 +/- 18.2 vs. 107.2 +/- 30.4 and 76.1 +/- 19.3 mmol/L/min; P
      < 0.05). Compared to water preload, the protein and fat preloads were associated
      with greater increases in plasma insulin, GLP-1 and glucagon concentrations, a
      reduction in BP, and greater increases in HR, fullness, bloating and nausea.
      Plasma 3-OMG levels were lower after the protein than after the water and fat
      preloads (P < 0.001). CONCLUSIONS: Given its effects to attenuate post-prandial
      glycaemia, reduce intestinal glucose absorption and potentiate the "incretin
      response", without inducing more adverse post-prandial GI symptom, protein
      preload may prove clinically useful in RYGB patients and warrant further
      evaluation, particularly in those with type 2 diabetes (T2DM) and/or dumping
      syndrome.

PMID- 25986428
TI  - Should We Abandon Routine Microscopic Examination in Bariatric Sleeve Gastrectomy
      Specimens?
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a relatively new bariatric
      surgical procedure to reduce weight in morbidly obese patients, with an overall
      low rate of complications and thus gaining a worldwide popularity. It provides an
      opportunity to study the pathology of the stomach in obese patients. Most
      studies, however, focused on clinical aspects, surgical techniques, and
      postoperative complications. Few authors studied the histopathologic findings.
      Whether routine histopathologic examination is warranted in patients with grossly
      unremarkable LSG specimens and nonsignificant clinical history was not previously
      studied. METHODS: We conducted a prospective study over 8 years to compare the
      prevalence, the morphologic spectrum and importance of histopathologic findings,
      and the frequency of incidental neoplasms in LSG specimens with other studies. We
      also proposed a protocol for the gross handling and sectioning of LSG specimens.
      RESULTS: We found 546 LSG specimens. Five patients developed iatrogenic
      postoperative complications, two of which pursued a medicolegal case. There was
      no association between the histopathologic findings and the complications. Less
      than 1 % of incidental benign lesions were found. No malignancies were
      identified. All of the patients without postoperative complications had
      uneventful outcome after 5 months to 6 years follow-up. CONCLUSIONS: Routine
      microscopic examination of all LSG specimens is not necessary. Selective
      microscopic examination guided by relevant clinical history and macroscopic
      examination is a better option. This protocol will save money, time, and workload
      without compromising patient's safety and future management. However, a careful
      gross description is still necessary in certain cases for potential future
      medicolegal implications.

PMID- 25986429
TI  - Long-Term Outcome of Laparoscopic Sleeve Gastrectomy in Morbidly Obese Japanese
      Patients.
AB  - BACKGROUND: Recently, laparoscopic sleeve gastrectomy (LSG) as a standalone
      bariatric procedure has rapidly gained popularity worldwide mainly because of its
      technical simplicity and the relatively good short-term outcome. In Japan,
      according to a domestic survey, 71 % of the bariatric procedures performed were
      LSG. However, the number of studies reporting long-term results are still not
      enough; particularly, data for Asian patients are scarce. OBJECTIVE: The
      objective of this study was to evaluate the long-term outcomes for LSG in
      morbidly obese Japanese regarding weight loss and safety. METHODS: Between
      October 2005 and July 2013, 179 morbidly obese Japanese patients (Female 89/Male
      90) underwent LSG as a standalone procedure. The mean age was 40.7 years (range,
      20-72 years), and the mean preoperative body weight and body mass index (BMI)
      were 120.4 kg (range, 71.4-231.6 kg) and 43.3 kg/m(2) (range, 30.9-76.5 kg/m(2)),
      respectively. All patients were evaluated and managed under a strict
      multidisciplinary team approach. RESULTS: The mean BMI declined to 30.0 +/- 8.7
      kg/m(2) at 1 year, 29.1 +/- 8.6 kg/m(2) at 2 years, 28.8 +/- 8.7 kg/m(2) at 3
      years, 29.3 +/- 9.2 kg/m(2) at 4 years, and 32.7 +/- 13.6 kg/m(2) at 5 years or
      more (p < 0.001). The mean percent total body weight loss (%TWL) achieved was
      32.4 +/- 12.9 % at 1 year, 34.3 +/- 12.9 % at 2 years, 34.4 +/- 11.6 % at 3
      years, 32.8 +/- 10.9 % at 4 years, and 29.5 +/- 11.8 % at 5 years or more. Super
      morbidly obese patients and patients whose gastric tube was created using a
      thicker (45 Fr.) bougie had a tendency to achieve less weight loss. Early and
      late complications occurred in 16 patients (8.9 %) and in seven patients (3.9 %),
      respectively. Revision surgeries were required in six patients (3.4 %). The
      reasons for revision surgery were insufficient weight loss in five patients and
      intractable gastroesophageal reflux disease (GERD) in one patient. CONCLUSION:
      LSG for Japanese morbidly obese patients is safe, effective, and acceptably
      durable up to 5 years although some complications unique to the procedure such as
      leakage from the staple line and intractable GERD occur. For super morbidly obese
      patients, other surgical options may be required.

PMID- 25986430
TI  - Sleeve Gastrectomy in Different Age Groups: a Comparative Study of 5-Year
      Outcomes.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been used more frequently
      over the past 10 years. As the population ages, a larger number of older people
      will suffer from weight-related comorbidities, resulting in bariatric surgery
      becoming a dominant solution for improving health and quality of life. We
      assessed the long-term outcomes of LSG in elderly patients. METHODS: We conducted
      a retrospective chart review of patients who underwent LSG between January 2007
      and August 2009. We subdivided 123 patients into <35 (n = 43), 35-55 (n = 59),
      and >55 (n = 21) age groups. RESULTS: The respective mean excess body mass index
      loss and excess weight loss were 42.5% +/- 3.1% and 41.3% +/- 12.3% for the <35
      age group, 48.7% +/- 4.1% and 45.6% +/- 10.6% for the 35-55 age group, and 53.6%
      +/- 4.6% and 52.1% +/- 11.1% for the >55 age group. The follow-up compliance
      rates at the 5-year visit were 23.85, 31.11, and 47.61% for the <35, 35-55, and
      >55 age groups, respectively. The corresponding Bariatric Analysis and Reporting
      Outcome System scores were 3.7 +/- 1.1, 4.0 +/- 0.7, and 5.3 +/- 1.3. The
      comorbidities of all the patients improved significantly, with a non-significant
      distribution between the three groups for each comorbidity. CONCLUSIONS: LSG is a
      useful tool for people who want to modify their eating habits and lose weight
      healthily. This study suggests that long-term weight loss, improvements in
      comorbidity, and compliance to follow-up are significant for patients >55 years
      old.

PMID- 25986431
TI  - Development and psychometric properties of the parent version of the Profile of
      Neuropsychiatric Symptoms (PONS) in children and adolescents.
AB  - BACKGROUND: The use of neuropsychiatric Patient Centred Outcome Measures (PCOMs)
      in routine child mental health and paediatric services is very time consuming and
      often requires multiple scales being completed as no single scale covers all
      areas of psychopathology. The use of a web-based programme can overcome these
      problems and contribute to improved use of PCOMs in clinical practice. We aim to
      develop a web-based scale (using HealthTrackerTM) to screen and identify young
      people with significant neuropsychiatric symptoms to enable early intervention.
      METHODS: Qualitative development of the Profile of Neuropsychiatric Symptoms
      (PONS) and quantitative evaluation of the psychometric properties of the PONS
      scale (parent version). Parents of 929 from the general population and 147 with
      neuropsychiatric disorders (5-18 years old) completed the PONS online. In
      addition, those children with neuropsychiatric disorders were assessed for the
      presence of current and lifetime psychiatric disorders using the Development and
      Well-Being Assessment (DAWBA). RESULTS: The PONS scale (parent version) consists
      of 30 symptom domains rated on a 7-point scale for both frequency and impairment.
      We found an intra-class correlation coefficient for single measures was 0.44
      (0.42-0.46 95 % CI, F = 22.84, p <= 0.0001) and for average measures was 0.96
      (0.95-0.96 95 % CI, F = 22.84, p <= 0.0001). The factor analysis showed a 4
      factor model: Neurodevelopmental Disability; Behavioural and Emotional
      Dysregulation; Psychoses and Personality Dysfunction; and Anxiety and Depression.
      The receiver operating characteristic area for the 4-factors was 0.96 (SE =
      0.006; 0.95-0.97 95 % CI). CONCLUSIONS: The PONS scale (parent version) is a web
      based PCOM on the HealthTrackerTM system that is a rapid, engaging measure that
      has excellent reliability and validity. The system allows for automated scoring
      and immediate feedback of statistical cut-off points and assists clinicians with
      diagnostic decision-making and optimises use of clinician time.

PMID- 25986432
TI  - A pilot study of the effects of mild systemic heating on human head and neck
      tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure,
      hypoxia and efficacy of radiation therapy.
AB  - PURPOSE: The tumour microenvironment is frequently hypoxic, poorly perfused, and
      exhibits abnormally high interstitial fluid pressure. These factors can
      significantly reduce efficacy of chemo and radiation therapies. The present study
      aims to determine whether mild systemic heating alters these parameters and
      improves response to radiation in human head and neck tumour xenografts in SCID
      mice. MATERIALS AND METHODS: SCID mice were injected with FaDu cells (a human
      head and neck carcinoma cell line), or implanted with a resected patient head and
      neck squamous cell carcinoma grown as a xenograft, followed by mild systemic
      heating. Body temperature during heating was maintained at 39.5 +/- 0.5  degrees
      C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour
      perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel
      perfusion was measured 24 h post-heating, coinciding with the first dose of
      fractionated radiotherapy. RESULTS: Heating tumour-bearing mice resulted in
      significant decrease in intratumoural IFP, increased the number of perfused
      tumour blood vessels as well as relative tumour perfusion in both tumour models.
      Intratumoural hypoxia was also reduced in tumours of mice that received heat
      treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation
      treatments exhibited significantly enhanced tumour response compared to tumours
      in control mice. CONCLUSIONS: Mild systemic heating can significantly alter the
      tumour microenvironment of human head and neck tumour xenograft models,
      decreasing IFP and hypoxia while increasing microvascular perfusion.
      Collectively, these effects could be responsible for the improved response to
      radiotherapy.

PMID- 25986433
TI  - Multi-scale homogenization of blood flow in 3-dimensional human cerebral
      microvascular networks.
AB  - The microvasculature plays a crucial role in the perfusion of blood through
      cerebral tissue. Current models of the cerebral microvasculature are discrete,
      and hence only able to model the perfusion over small voxel sizes before becoming
      computationally prohibitive. Larger models are required to provide comparisons
      and validation against imaging data. In this work, multi-scale homogenization
      methods were employed to develop continuum models of blood flow in a capillary
      network model of the human cortex. Homogenization of the local scale blood flow
      equations produced an averaged form of Darcy's law, with the permeability tensor
      encapsulating the capillary bed topology. A statistically accurate network model
      of the human cortex microvasculature was adapted to impose periodicity, and the
      elements of the permeability tensor calculated over a range of voxel sizes. The
      permeability tensor was found to converge to an effective permeability as voxel
      size increased. This converged permeability tensor was isotropic, reflecting the
      mesh-like structure of the cerebral microvasculature, with off-diagonal terms
      normally distributed about zero. A representative elementary volume of 375um,
      with a standard deviation of 4.5% from the effective permeability, was
      determined. Using the converged permeability values, the cerebral blood flow was
      calculated to be around 55mLmin(-1)100g(-1), which is in very close agreement
      with experimental values. These results open up the possibility of future multi
      scale modeling of the cerebral vascular network. 

PMID- 25986434
TI  - Interstitial hydraulic conductivity and interstitial fluid pressure for avascular
      or poorly vascularized tumors.
AB  - A correct description of the hydraulic conductivity is essential for determining
      the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally,
      it has been assumed that the hydraulic conductivities both in a tumor and normal
      tissue are constant, and that a tumor has a much larger interstitial hydraulic
      conductivity than normal tissue. The abrupt transition of the hydraulic
      conductivity at the tumor surface leads to non-physical results (the hydraulic
      conductivity and the slope of the TIFP are not continuous at tumor surface). For
      the sake of simplicity and the need to represent reality, we focus our analysis
      on avascular or poorly vascularized tumors, which have a necrosis that is mostly
      in the center and vascularization that is mostly on the periphery. We suggest
      that there is an intermediary region between the tumor surface and normal tissue.
      Through this region, the interstitium (including the structure and composition of
      solid components and interstitial fluid) transitions from tumor to normal tissue.
      This process also causes the hydraulic conductivity to do the same. We introduce
      a continuous variation of the hydraulic conductivity, and show that the
      interstitial hydraulic conductivity in the intermediary region should be
      monotonically increasing up to the value of hydraulic conductivity in the normal
      tissue in order for the model to correspond to the actual TIFP distribution. The
      value of the hydraulic conductivity at the tumor surface should be the lowest in
      value. 

PMID- 25986435
TI  - Human mesenchymal stromal cells decrease the severity of acute lung injury
      induced by E. coli in the rat.
AB  - BACKGROUND: Mesenchymal stromal cells (MSCs) demonstrate considerable promise in
      preclinical acute respiratory distress syndrome models. We wished to determine
      the efficacy and mechanisms of action of human MSCs (hMSCs) in the setting of
      acute lung injury induced by prolonged Escherichia coli pneumonia in the rat.
      METHODS: Adult male Sprague Dawley rats underwent intratracheal instillation of
      E. coli bacteria in all experiments. In Series 1, animals were randomised to
      intravenous administration of: (1) vehicle (phosphate buffered saline (PBS), 300
      MUL); (2) 1*10(7) fibroblasts/kg; (3) 1*10(7) hMSCs/kg or (4) 2*10(7) hMSCs/kg.
      Series 2 determined the lowest effective hMSC dose. Series 3 compared the
      efficacy of intratracheal versus intravenous hMSC administration, while Series 4
      examined the efficacy of cryopreserved hMSC. Series 5 examined the efficacy of
      the hMSC secretome. Parallel in vitro experiments further assessed the potential
      for hMSCs to secrete LL-37 and modulate macrophage phagocytosis. RESULTS: hMSC
      therapy reduced the severity of rodent E. coli pneumonia, improving survival,
      decreasing lung injury, reducing lung bacterial load and suppressing
      inflammation. Doses as low as 5*10(6) hMSCs/kg were effective. Intratracheal hMSC
      therapy was as effective as intravenous hMSC. Cryopreserved hMSCs were also
      effective, while the hMSC secretome was less effective in this model. hMSC
      therapy enhanced macrophage phagocytic capacity and increased lung and systemic
      concentrations of the antimicrobial peptide LL37. CONCLUSIONS: hMSC therapy
      decreased E. coli induced pneumonia injury and reduced lung bacterial burden,
      potentially via enhanced macrophage phagocytosis and increased alveolar LL-37
      concentrations.

PMID- 25986437
TI  - Comment on "Severe dental fluorosis and cognitive deficits".

PMID- 25986436
TI  - Association of sleep characteristics with atrial fibrillation: the Multi-Ethnic
      Study of Atherosclerosis.
AB  - BACKGROUND: Population-based studies have linked measures of sleep disordered
      breathing to nocturnally occurring atrial fibrillation (AF) episodes. Whether
      measures of sleep disordered breathing and sleep quality are associated with
      prevalent AF has not been studied in an unselected population. We investigated
      the cross-sectional association with prevalent AF of objectively collected
      prespecified measures of overnight sleep breathing disturbances, sleep stage
      distributions, arousal and sleep duration. METHODS: AF prevalence, defined by
      diagnosis codes, study electrocardiography and sleep study were examined among
      Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent
      polysomnography in the MESA Sleep Study (n=2048). MEASUREMENTS AND MAIN RESULTS:
      Higher apnoea hypopnoea index (AHI) was associated with increased odds of AF,
      although the significance was attenuated after full adjustment for covariates
      including prevalent cardiovascular disease (OR: 1.22 (0.99 to 1.49) per SD
      (17/h), p=0.06). Analyses of sleep architecture measures and AF revealed
      significantly lower odds of AF associated with longer duration of slow wave sleep
      (OR: 0.66 (0.5 to 0.89) per SD (34 min), p=0.01) which persisted after
      additionally adjusting for AHI (OR: 0.68 (0.51 to 0.92), p=0.01). Higher sleep
      efficiency was significantly associated with lower likelihood of AF but the
      significance was lost when adjusted for AHI. No significant association was
      present between sleep duration and AF. In a model including AHI and arousal
      index, the association between AHI and AF was strengthened (AHI: OR 1.49 (1.15 to
      1.91) per SD, p=0.002) and a significant inverse association between arousal
      index and AF was observed (OR 0.65 (0.50 to 0.86) per SD (12/h), p=0.005).
      CONCLUSIONS: In a study of a large multiethnic population, AF was associated with
      AHI severity, and was more common in individuals with poor sleep quality as
      measured by reduced slow wave sleep time, a finding that was independent of AHI.

PMID- 25986439
TI  - Erratum to: Copy number variation in the human Y chromosome in the UK population.

PMID- 25986440
TI  - Prognostic factors of head and neck sarcomas.

PMID- 25986441
TI  - A sea urchin Na(+)K(+)2Cl(-) cotransporter is involved in the maintenance of
      calcification-relevant cytoplasmic cords in Strongylocentrotus droebachiensis
      larvae.
AB  - The cellular mechanisms of calcification in sea urchin larvae are still not well
      understood. Primary mesenchyme cells within the larval body cavity form a
      syncytium to secrete CaCO3 spicules from intracellular amorphous CaCO3 (ACC)
      stores. We studied the role of Na(+)K(+)2Cl(-) cotransporter (NKCC) in
      intracellular ACC accumulation and larval spicule formation of Strongylocentrotus
      droebachiensis. First, we incubated growing larvae with three different loop
      diuretics (azosemide, bumetanide, and furosemide) and established concentration
      response curves. All loop diuretics were able to inhibit calcification already at
      concentrations that specifically inhibit NKCC. Calcification was most effectively
      inhibited by azosemide (IC50=6.5 MUM), while larval mortality and swimming
      ability were not negatively impacted by the treatment. The inhibition by
      bumetanide (IC50=26.4 MUM) and furosemide (IC50=315.4 MUM) resembled the
      pharmacological fingerprint of the mammalian NKCC1 isoform. We further examined
      the effect of azosemide on the maintenance of cytoplasmic cords and on the
      occurrence of calcification vesicles using fluorescent dyes (calcein, FM1-43).
      Fifty micromolars of azosemide inhibited the maintenance of cytoplasmic cords and
      resulted in increased calcein fluorescence within calcification vesicles. The
      expression of NKCC in S. droebachiensis was verified by PCR and Western blot with
      a specific NKCC antibody. In summary, the pharmacological profile of loop
      diuretics and their specific effects on calcification in sea urchin larvae
      suggest that they act by inhibition of NKCC via repression of cytoplasmic cord
      formation and maintenance.

PMID- 25986438
TI  - Telomere length and common disease: study design and analytical challenges.
AB  - Telomeres, the repetitive sequences that protect the ends of chromosomes, help to
      maintain genomic integrity and are of key importance to human health. The aim
      here is to give an overview of the evidence for the importance of telomere length
      (TL) to the risk of common disease, considering the strengths and weaknesses of
      different epidemiological study designs. Methods for measuring TL are described,
      all of which are subject to considerable measurement error. TL declines with age
      and varies in relation to factors such as smoking and obesity. It is also highly
      heritable (estimated heritability of ~40 to 50%), and genome-wide studies have
      identified a number of associated genetic variants. Epidemiological studies have
      shown shorter TL to be associated with risk of a number of common diseases,
      including cardiovascular disease and some cancers. The relationship with cancer
      appears complex, in that longer telomeres are associated with higher risk of some
      cancers. Prospective studies of the relationship between TL and disease, where TL
      is measured before diagnosis, have numerous advantages over retrospective
      studies, since they avoid the problems of reverse causality and differences in
      sample handling, but they are still subject to potential confounding. Studies of
      the genetic predictors of TL in relation to disease risk avoid these drawbacks,
      although they are not without limitations. Telomere biology is of major
      importance to the risk of common disease, but the complexities of the
      relationship are only now beginning to be understood.

PMID- 25986442
TI  - Evaluating Guideline-Recommended Antibiotic Practices for Childhood Respiratory
      Infections: Is It Time to Consider Case-Based Formats?
AB  - OBJECTIVE: We sought to better understand barriers to adherence to published
      guidelines for respiratory infections among community providers. METHODS: A case
      based survey was developed and emailed to all members of the state pediatric
      society. Providers chose their preferred management for acute otitis media, acute
      bacterial sinusitis, and community-acquired pneumonia. An "answer key" and a
      follow-up questionnaire were distributed to assess reevaluation of current
      practices. RESULTS: We received 173 completed surveys (15% response rate). While
      most responders followed guideline recommendations (6 of the 10 questions with >=
      65% choosing recommended antibiotic), discrepancies existed in several cases.
      After receiving the answer key, respondents said they reviewed the guidelines
      (69%), adjusted their practice (26%), used cases for teaching (9%), and discussed
      guidelines with colleagues (21%). CONCLUSIONS: The majority of respondents
      followed published guidelines, but there was a tendency to overuse azithromycin
      in certain cases. Future guidelines including case-based discussions may enhance
      adherence.

PMID- 25986443
TI  - Validation and Assessment of Pediatric Lead Screener Questions for Primary
      Prevention of Lead Exposure.
AB  - OBJECTIVE: Pediatric lead screener questions have previously been evaluated for
      their ability to identify children whose blood lead levels (BLLs) are greater
      than 10 ug/dL. Based on recent policy changes stressing that there is no safe BLL
      for children, the current study reevaluates the screener questions for their
      ability to identify children with BLLs less than 2 ug/dL and the validity of the
      questions in positively identifying those at greater risk for exposure. METHOD: A
      total of 202 parents of children enrolled in Head Start programs were
      administered the pediatric lead screener, questions to validate the screener
      questions, and children's BLLs were collected in Summer 2013. Pediatric screener
      questions were validated against children's BLL and the more comprehensive
      questions on lead risk. RESULTS: In predicting BLL greater than 2 ug/dL, the
      pediatrician screener tool had a sensitivity of 26.3% and specificity of 72.2%.
      Each of the screener questions had low sensitivities for identifying children
      with BLLs above 2 ug/dL. The screener questions did not demonstrate adequate
      validity when compared against a more comprehensive battery of lead exposure risk
      indicators. The validation questions improved sensitivity to detect children with
      BLL >2 ug/dL and reduced the number of false positives. CONCLUSION: The
      pediatrician screener questions in their current format are not a useful primary
      prevention tool in identifying children at greater risk for lead exposure and in
      need of secondary prevention through the receipt of a blood lead test. A revision
      to the protocol for identifying children at risk could result in better primary
      and secondary prevention efforts.

PMID- 25986445
TI  - In Vitro and In Vivo Evidence for Active Brain Uptake of the GHB Analog HOCPCA by
      the Monocarboxylate Transporter Subtype 1.
AB  - gamma-Hydroxybutyric acid (GHB) is a recreational drug, a clinically prescribed
      drug in narcolepsy and alcohol dependence, and an endogenous substance that binds
      to both high- and low-affinity sites in the brain. For studying the molecular
      mechanisms and the biologic role of the GHB high-affinity binding sites, ligands
      with high and specific affinity are essential. The conformationally restricted
      GHB analog HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) is one such compound.
      The objective of this study was to investigate the transport of HOCPCA across the
      blood-brain barrier in vitro and in vivo and to investigate the hypothesis that
      HOCPCA, like GHB, is a substrate for the monocarboxylate transporters (MCTs). For
      in vitro uptake studies, MCT1, -2, and -4 were recombinantly expressed in Xenopus
      laevis oocytes, and the previously reported radioligand [(3)H]HOCPCA was used as
      substrate. HOCPCA inhibited the uptake of the endogenous MCT substrate l
      [(14)C]lactate, and [(3)H]HOCPCA was shown to act as substrate for MCT1 and 2 (Km
      values in the low- to mid-millimolar range). Introducing single-point amino acid
      mutations into positions essential for MCT function supported that HOCPCA binds
      to the endogenous substrate pocket of MCTs. MCT1-mediated brain entry of HOCPCA
      (10 mg/kg s.c.) was further confirmed in vivo in mice by coadministration of
      increasing doses of the MCT inhibitor AR-C141990 [(R)-5-(3-hydroxypyrrolidine-1
      carbonyl)-1-isobutyl-3-methyl-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine
      2,4(1H,3H)-dione], which inhibited brain penetration of HOCPCA in a dose
      dependent manner (ID50 = 4.6 mg/kg). Overall, our study provides evidence that
      MCT1 is an important brain entry site for HOCPCA and qualifies for future in vivo
      studies with HOCPCA. 

PMID- 25986444
TI  - Evidence for a distinct neuro-immune signature in rats that develop behavioural
      disability after nerve injury.
AB  - BACKGROUND: Chronic neuropathic pain is a neuro-immune disorder, characterised by
      allodynia, hyperalgesia and spontaneous pain, as well as debilitating affective
      motivational disturbances (e.g., reduced social interactions, sleep-wake cycle
      disruption, anhedonia, and depression). The role of the immune system in altered
      sensation following nerve injury is well documented. However, its role in the
      development of affective-motivational disturbances remains largely unknown. Here,
      we aimed to characterise changes in the immune response at peripheral and spinal
      sites in a rat model of neuropathic pain and disability. METHODS: Sixty-two rats
      underwent sciatic nerve chronic constriction injury (CCI) and were characterised
      as either Pain and disability, Pain and transient disability or Pain alone on the
      basis of sensory threshold testing and changes in post-CCI dominance behaviour in
      resident-intruder interactions. Nerve ultrastructure was assessed and the number
      of T lymphocytes and macrophages were quantified at the site of injury on day six
      post-CCI. ATF3 expression was quantified in the dorsal root ganglia (DRG). Using
      a multiplex assay, eight cytokines were quantified in the sciatic nerve, DRG and
      spinal cord. RESULTS: All CCI rats displayed equal levels of mechanical
      allodynia, structural nerve damage, and reorganisation. All CCI rats had
      significant infiltration of macrophages and T lymphocytes to both the injury site
      and the DRG. Pain and disability rats had significantly greater numbers of T
      lymphocytes. CCI increased IL-6 and MCP-1 in the sciatic nerve. Examination of
      disability subgroups revealed increases in IL-6 and MCP-1 were restricted to Pain
      and disability rats. Conversely, CCI led to a decrease in IL-17, which was
      restricted to Pain and transient disability and Pain alone rats. CCI
      significantly increased IL-6 and MCP-1 in the DRG, with IL-6 restricted to Pain
      and disability rats. CCI rats had increased IL-1beta, IL-6 and MCP-1 in the
      spinal cord. Amongst subgroups, only Pain and disability rats had increased IL
      1beta. CONCLUSIONS: This study has defined individual differences in the immune
      response at peripheral and spinal sites following CCI in rats. These changes
      correlated with the degree of disability. Our data suggest that individual immune
      signatures play a significant role in the different behavioural trajectories
      following nerve injury, and in some cases may lead to persistent affective
      motivational disturbances.

PMID- 25986446
TI  - Xanthine oxidase inhibitors in heart failure: where do we go from here?

PMID- 25986449
TI  - ECG Response: May 19, 2015.

PMID- 25986448
TI  - Hospital readmissions reduction program.

PMID- 25986450
TI  - Reconstruction of an extracardiac aortocoronary collateral and simulation of
      selective angiography with multidetector-row computed tomography.

PMID- 25986451
TI  - Letter by Fenici et al Regarding Articles, "Wolff-Parkinson-White Syndrome in the
      Era of Catheter Ablation: Insights From a Registry Study of 2169 Patients" and
      "The Asymptomatic Wolff-Parkinson-White Patient: Time to be More Proactive?".

PMID- 25986447
TI  - Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients:
      The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT
      HF) Study.
AB  - BACKGROUND: Oxidative stress may contribute to heart failure (HF) progression.
      Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes.
      METHODS AND RESULTS: We randomly assigned 253 patients with symptomatic HF, left
      ventricular ejection fraction <=40%, and serum uric acid levels >=9.5 mg/dL to
      receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind,
      multicenter trial. The primary composite end point at 24 weeks was based on
      survival, worsening HF, and patient global assessment. Secondary end points
      included change in quality of life, submaximal exercise capacity, and left
      ventricular ejection fraction. Uric acid levels were significantly reduced with
      allopurinol in comparison with placebo (treatment difference, -4.2 [-4.9, -3.5]
      mg/dL and -3.5 [-4.2, -2.7] mg/dL at 12 and 24 weeks, respectively, both
      P<0.0001). At 24 weeks, there was no significant difference in clinical status
      between the allopurinol- and placebo-treated patients (worsened 45% versus 46%,
      unchanged 42% versus 34%, improved 13% versus 19%, respectively; P=0.68). At 12
      and 24 weeks, there was no significant difference in change in Kansas City
      Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2
      groups. At 24 weeks, left ventricular ejection fraction did not change in either
      group or between groups. Rash occurred more frequently with allopurinol (10%
      versus 2%, P=0.01), but there was no difference in serious adverse event rates
      between the groups (20% versus 15%, P=0.36). CONCLUSIONS: In high-risk HF
      patients with reduced ejection fraction and elevated uric acid levels, xanthine
      oxidase inhibition with allopurinol failed to improve clinical status, exercise
      capacity, quality of life, or left ventricular ejection fraction at 24 weeks.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00987415.

PMID- 25986452
TI  - Response to letter regarding article, "Wolff-Parkinson-White syndrome in the era
      of catheter ablation: insights from a registry study of 2169 patients".

PMID- 25986453
TI  - Response to Letter Regarding Editorial, "The Asymptomatic Wolff-Parkinson-White
      Patient: Time to be More Proactive?".

PMID- 25986454
TI  - Correction.
AB  - In the article by Gale et al, "Mental Disorders Across the Adult Life Course and
      Future Coronary Heart Disease: Evidence for General Susceptibility," which was
      published in the January 14, 2014 issue of the journal (Circulation. 2014;129:186
      193. DOI: 10.1161/CIRCULATION AHA.113.002065), there were errors in reporting
      some of the results. Specifically, due to coding mistakes during programming,
      there were errors in the number of men reported as having been diagnosed with
      some forms of mental disorder at the conscription examination in early adulthood.

PMID- 25986455
TI  - Correction.
AB  - In the article by Ristagno et al, "Amplitude Spectrum Area to Guide
      Defibrillation: A Validation on 1617 Patients With Ventricular Fibrillation,"
      which was published in the February 3, 2015 issue of the journal (Circulation.
      2015;131:478-487. DOI: 10.1161/CIRCULATION AHA.114.010989), the authors wish to
      report an error in Table V of the online-only Data Supplement. Association of
      AMSA with defibrillation success was independent of the features of the
      defibrillators, although the type A and B defibrillators accounted for a
      significantly higher AUC compared with type C defibrillator. Table V in the
      online-only Data Supplement has been corrected accordingly. The authors regret
      this error.(

PMID- 25986457
TI  - Acute management of traumatic cervical spinal cord injury.
AB  - Patients with acute cervical spinal cord injury present complex clinical
      challenges. These injuries may result in motor and sensory deficits and also in
      cardiovascular and respiratory perturbations. Increased attention to critical
      care support has led to improved survival and recovery in many patients. The
      methods and technology used to diagnose and classify these injuries as well as
      medical and surgical treatments have evolved significantly in recent decades. We
      review important aspects of the diagnosis and acute care of patients with
      traumatic cervical spinal cord injuries, emphasising the recent evidence. 

PMID- 25986456
TI  - The international Hip Outcome Tool-33 (iHOT-33): multicenter validation and
      translation to Spanish.
AB  - BACKGROUND: The international Hip Outcome Tool-33 (iHOT-33) is a 33-item self
      administered outcome measure based on a Visual Analogue Scale response format
      designed for young and active population with hip pathology. The aim of the
      present study is to translate and validate the iHOT-33 into Spanish. METHODS: 97
      patients undergoing hip arthroscopy were included in this prospective and
      multicenter study performed between January 2012 and May 2014. Crosscultural
      adaptation was used to translate iHOT-33 into Spanish. Patients completed the
      questionnaire before and after surgery. Feasibility, reliability, internal
      consistency, construct validity (correlation with Western Ontario and McMaster
      Universities Osteoarthritis Index), ceiling and floor effects and sensitivity to
      change were assessed for the present study. RESULTS: Mean age was 48 years old.
      Feasibility: 41.2 % patients had no blank questions, and 71.3 % of patients had
      fulfilled all but one or two questions. Reliability: ICC for the global
      questionnaire was 0.97, showing that the questionnaire is highly reproducible.
      Internal consistency: Cronbach's alpha was 0.98 for the global questionnaire.
      Construct validity: there was a high correlation with WOMAC (correlation
      coefficient >0.5). The Ceiling effect (taking into account the minimum detectable
      change) was 12.1 % and the floor effect was 21.6 %, for the global questionnaire.
      Large sensitivity to change was shown. CONCLUSION: the Spanish version of iHOT-33
      has shown to be feasible, reliable and sensible to changes for patients
      undergoing hip arthroscopy. This validated translation of iHOT-33 allows for
      comparisons between studies involving either Spanish- or English-speaking
      patients. LEVEL OF EVIDENCE: Prognostic study, Level I.

PMID- 25986458
TI  - The association between antibody levels before and after 7-valent pneumococcal
      conjugate vaccine immunization and subsequent pneumococcal infection in chronic
      arthritis patients.
AB  - INTRODUCTION: The aim of present study is to inverstigate the association between
      antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine
      (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis
      (RA) and spondylarthropathy (SpA) patients. METHODS: A cohort of 497 patients
      (RA=248 and SpA=249) received a single dose of PCV7. At vaccination, patients
      were treated with methotrexate (MTX; n=85), anti-tumour necrosis factor (anti
      TNF) + MTX (n=169), anti-TNF monotherapy (n=158) and non-steroidal anti
      inflammatory drugs (NSAIDs)/analgesics (n=85). Antibody levels of serotypes 6B
      and 23B were analyzed before and 4 to 6 weeks after vaccination using standard
      enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections
      (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic
      arthritis) occurring within 4.5 years after vaccination were identified in the
      Skane Healthcare Register using the International Classification of Diseases,
      tenth revision (ICD-10) codes. The association between post-vaccination antibody
      levels and protection against infections and determination of protective cutoff
      levels was explored using receiver operating characteristic (ROC) curves.
      Predictors of infection were studied using regression analyses. RESULTS: Eighteen
      infections were registered in 15 patients before vaccination and 27 infections in
      23 patients after vaccination. Patients with serious infections after vaccination
      had significantly lower post-vaccination antibody titres for both 6B (P=0.04) and
      23 F (P=0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01
      mg/L for 6B and 23, respectively, were associated with better protection from
      serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF
      were associated with such infections. CONCLUSIONS: Patients with more robust
      antibody responses after vaccination with pneumococcal conjugate vaccine were
      less likely to suffer from serious infections. High age and prednisolone at
      vaccination were associated with putative serious pneumococcal infections in this
      cohort. TRIAL REGISTRATION NUMBER: EudraCT EU 2007-006539-29 and NCT00828997 .
      Registered 23 January 2009.

PMID- 25986459
TI  - Glyphosate's impact on vegetative growth in leafy spurge identifies molecular
      processes and hormone cross-talk associated with increased branching.
AB  - BACKGROUND: Leafy spurge (Euphorbia esula) is a perennial weed that is considered
      glyphosate tolerant, which is partially attributed to escape through
      establishment of new vegetative shoots from an abundance of underground
      adventitious buds. Leafy spurge plants treated with sub-lethal concentrations of
      foliar-applied glyphosate produce new vegetative shoots with reduced main stem
      elongation and increased branching. Processes associated with the glyphosate
      induced phenotype were determined by RNAseq using aerial shoots derived from
      crown buds of glyphosate-treated and -untreated plants. Comparison between
      transcript abundance and accumulation of shikimate or phytohormones (abscisic
      acid, auxin, cytokinins, and gibberellins) from these same samples was also done
      to reveal correlations. RESULTS: Transcriptome assembly and analyses confirmed
      differential abundance among 12,918 transcripts (FDR <= 0.05) and highlighted
      numerous processes associated with shoot apical meristem maintenance and stem
      growth, which is consistent with the increased number of actively growing
      meristems in response to glyphosate. Foliar applied glyphosate increased
      shikimate abundance in crown buds prior to decapitation of aboveground shoots,
      which induces growth from these buds, indicating that 5-enolpyruvylshikimate 3
      phosphate (EPSPS) the target site of glyphosate was inhibited. However, abundance
      of shikimate was similar in a subsequent generation of aerial shoots derived from
      crown buds of treated and untreated plants, suggesting EPSPS is no longer
      inhibited or abundance of shikimate initially observed in crown buds dissipated
      over time. Overall, auxins, gibberellins (precursors and catabolites of bioactive
      gibberellins), and cytokinins (precursors and bioactive cytokinins) were more
      abundant in the aboveground shoots derived from glyphosate-treated plants.
      CONCLUSION: Based on the overall data, we propose that the glyphosate-induced
      phenotype resulted from complex interactions involving shoot apical meristem
      maintenance, hormone biosynthesis and signaling (auxin, cytokinins, gibberellins,
      and strigolactones), cellular transport, and detoxification mechanisms.

PMID- 25986460
TI  - Quantitative assessment of background parenchymal enhancement in breast MRI
      predicts response to risk-reducing salpingo-oophorectomy: preliminary evaluation
      in a cohort of BRCA1/2 mutation carriers.
AB  - INTRODUCTION: We present a fully automated method for deriving quantitative
      measures of background parenchymal enhancement (BPE) from breast dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) and perform a preliminary
      evaluation of these measures to assess the effect of risk-reducing salpingo
      oophorectomy (RRSO) in a cohort of breast cancer susceptibility gene 1/2
      (BRCA1/2) mutation carriers. METHODS: Breast DCE-MRI data from 50 BRCA1/2
      carriers were retrospectively analyzed in compliance with the Health Insurance
      Portability and Accountability Act and with institutional review board approval.
      Both the absolute (| |) and relative (%) measures of BPE and fibroglandular
      tissue (FGT) were computed from the MRI scans acquired before and after RRSO.
      These pre-RRSO and post-RRSO measures were compared using paired Student's t
      test. The area under the curve (AUC) of the receiver operating characteristic
      (ROC) was used to evaluate the performance of relative changes in the BPE and FGT
      measures in predicting breast cancer that developed in these women after the RRSO
      surgery. RESULTS: For the 44 women who did not develop breast cancer after RRSO,
      the absolute volume of BPE and FGT had a significant decrease (P < 0.05) post
      RRSO, whereas for the 6 women who developed breast cancer, there were no
      significant changes in these measures. Higher values in all BPE and FGT measures
      were also observed post-RRSO for the women who developed breast cancer, compared
      with women who did not. Relative changes in BPE percentage were most predictive
      of women who developed breast cancer after RRSO (P < 0.05), whereas combining BPE
      percentage and |FGT| yielded an AUC of 0.80, higher than BPE percentage (AUC =
      0.78) or |FGT| (AUC = 0.66) alone (both P > 0.02). CONCLUSIONS: Quantitative
      measures of BPE and FGT are different before and after RRSO, and their relative
      changes are associated with prediction of developing breast cancer, potentially
      indicative of women who are more susceptible to develop breast cancer after RRSO
      in BRCA1/2 mutation carriers.

PMID- 25986461
TI  - Neuroregenerative effects of olfactory ensheathing cells transplanted in a multi
      layered conductive nanofibrous conduit in peripheral nerve repair in rats.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of a multi
      layered conductive nanofibrous hollow conduit in combination with olfactory
      ensheathing cells (OEC) to promote peripheral nerve regeneration. We aimed to
      harness both the topographical and electrical cues of the aligned conductive
      nanofibrous single-walled carbon nanotube/ poly (L-lactic acid) (SWCNT/PLLA)
      scaffolds along with the neurotrophic features of OEC in a nerve tissue
      engineered approach. RESULTS: We demonstrated that SWCNT/PLLA composite scaffolds
      support the adhesion, growth, survival and proliferation of OEC. Using
      microsurgical techniques, the tissue engineered nerve conduits were interposed
      into an 8 mm gap in sciatic nerve defects in rats. Functional recovery was
      evaluated using sciatic functional index (SFI) fortnightly after the surgery.
      Histological analyses including immunohistochemistry for S100 and NF markers
      along with toluidine blue staining (nerve thickness) and TEM imaging (myelin
      sheath thickness) of the sections from middle and distal parts of nerve grafts
      showed an increased regeneration in cell/scaffold group compared with cell-free
      scaffold and silicone groups. Neural regeneration in cell/scaffold group was very
      closely similar to autograft group, as deduced from SFI scores and histological
      assessments. CONCLUSIONS: Our results indicated that the tissue engineered
      construct made of rolled sheet of SWCNT/PLLA nanofibrous scaffolds and OEC could
      promote axonal outgrowth and peripheral nerve regeneration suggesting them as a
      promising alternative in nerve tissue engineering.

PMID- 25986462
TI  - Three- to nine-year survival estimates and fracture mechanisms of zirconia- and
      alumina-based restorations using standardized criteria to distinguish the
      severity of ceramic fractures.
AB  - OBJECTIVES: The aims of this study were set as follows: 1. To provide verifiable
      criteria to categorize the ceramic fractures into non-critical (i.e., amenable to
      polishing) or critical (i.e., in need of replacement) 2. To establish the
      corresponding survival rates for alumina and zirconia restorations 3. To
      establish the mechanism of fracture using fractography MATERIALS AND METHODS:
      Fifty-eight patients restored with 115 alumina-/zirconia-based crowns and 26
      zirconia-based fixed dental prostheses (FDPs) were included. Ceramic fractures
      were classified into four types and further subclassified into "critical" or "non
      critical." Kaplan-Meier survival estimates were calculated for "critical
      fractures only" and "all fractures." Intra-oral replicas were taken for
      fractographic analyses. RESULTS: Kaplan-Meier survival estimates for "critical
      fractures only" and "all fractures" were respectively: Alumina single crowns:
      90.9 and 68.3 % after 9.5 years (mean 5.71 +/- 2.6 years). Zirconia single
      crowns: 89.4 and 80.9 % after 6.3 years (mean 3.88 +/- 1.2 years). Zirconia FDPs:
      68.6 % (critical fractures) and 24.6 % (all fractures) after 7.2 and 4.6 years
      respectively (FDP mean observation time 3.02 +/- 1.4 years). No core/framework
      fractures were detected. CONCLUSIONS: Survival estimates varied significantly
      depending on whether "all" fractures were considered as failures or only those
      deemed as "critical". For all restorations, fractographic analyses of failed
      veneering ceramics systematically demonstrated heavy occlusal wear at the failure
      origin. Therefore, the relief of local contact pressures on unsupported ceramic
      is recommended. Occlusal contacts on mesial or distal ridges should
      systematically be eliminated. CLINICAL RELEVANCE: A classification standard for
      ceramic fractures into four categories with subtypes "critical" and "non
      critical" provides a differentiated view of the survival of ceramic restorations.

PMID- 25986464
TI  - Needle Tract Seeding Following Irreversible Electroporation (IRE) of Metastatic
      Colorectal Carcinoma to the Liver.

PMID- 25986463
TI  - Intrapulmonary administration of bone-marrow derived M1/M2 macrophages to enhance
      the resolution of LPS-induced lung inflammation: noninvasive monitoring using
      free-breathing MR and CT imaging protocols.
AB  - BACKGROUND: Alveolar macrophages, with their high functional plasticity, were
      reported to orchestrate the induction and resolution of inflammatory processes in
      chronic pulmonary diseases. Noninvasive imaging modalities that offer
      simultaneous monitoring of inflammation progression and tracking of macrophages
      subpopulations involved in the inflammatory cascade, can provide an ideal and
      specific diagnostic tool to visualize the action mechanism in its initial stages.
      Therefore, the purpose of the current study was to evaluate the role of M1 and M2
      macrophages in the resolution of lipopolysaccharide (LPS)-induced lung
      inflammation and monitor this process using noninvasive free-breathing MRI and CT
      protocols. METHODS: Bone-marrow derived macrophages were first polarized to M1
      and M2 macrophages and then labeled with superparamagnetic iron oxide
      nanoparticles. BALB/c mice with lung inflammation received an intrapulmonary
      instillation of these ex vivo polarized M1 or M2 macrophages. The biodistribution
      of macrophages subpopulations and the subsequent resolution of lung inflammation
      were noninvasively monitored using MRI and micro-CT. Confirmatory
      immunohistochemistry analyses were performed on lung tissue sections using
      specific macrophage markers. RESULTS: As expected, large inflammatory areas
      noninvasively imaged using pulmonary MR and micro-CT were observed within the
      lungs following LPS challenge. Subsequent intrapulmonary administration of M1 and
      M2 macrophages resulted in a significant decrease in inflammation starting from
      72 h. Confirmatory immunohistochemistry analyses established a progression of
      lung inflammation with LPS and its subsequent reduction with both macrophages
      subsets. An enhanced resolution of inflammation was observed with M2 macrophages
      compared to M1. CONCLUSIONS: The current study demonstrated that ex vivo
      polarized macrophages decreased LPS-induced lung inflammation. Noninvasive free
      breathing MR and CT imaging protocols enabled efficient monitoring of progression
      and resolution of lung inflammation.

PMID- 25986465
TI  - Safety of Radioembolization with (90)Yttrium Resin Microspheres Depending on
      Coiling or No-Coiling of Aberrant/High-Risk Vessels.
AB  - PURPOSE: To evaluate the safety of radioembolization (RE) with (90)Yttrium
      ((90)Y) resin microspheres depending on coiling or no-coiling of aberrant/high
      risk vessels. MATERIALS AND METHODS: Early and late toxicity after 566 RE
      procedures were analyzed retrospectively in accordance with the National Cancer
      Institute's Common Terminology Criteria for Adverse Events (CTCAE v3.0). For
      optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling
      group) or a more peripheral position of the catheter tip was chosen to treat
      right or left liver lobes (n = 326/566, no-coiling group). RESULTS: Clinically
      relevant late toxicities (>= Grade 3) were observed in 1% of our overall cohort.
      The no-coiling group had significantly less "any" (P = 0.0001) or "clinically
      relevant" (P = 0.0003) early toxicity. There was no significant difference (P >
      0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE
      induced liver disease was noted after all 566 procedures. CONCLUSION: RE with
      (90)Y resin microspheres is a safe and effective treatment option. Performing RE
      without coil embolization of aberrant vessels prior to treatment could be an
      alternative for experienced centers.

PMID- 25986467
TI  - A stable fluorinated and alkylated lithium malonatoborate salt for lithium ion
      battery application.
AB  - A new fluorinated and alkylated lithium malonatoborate salt, lithium bis(2-methyl
      2-fluoromalonato)borate (LiBMFMB), has been synthesized for lithium ion battery
      application. A 0.8 M LiBMFMB solution is obtained in a mixture of ethylene
      carbonate (EC) and ethyl methyl carbonate (EMC) (1 : 2 by wt). The new LiBMFMB
      based electrolyte exhibits good cycling stability and rate capability in
      LiNi0.5Mn1.5O4 and graphite based half-cells.

PMID- 25986466
TI  - Nutrition promotion approaches preferred by Australian adolescents attending
      schools in disadvantaged neighbourhoods: a qualitative study.
AB  - BACKGROUND: Links between socioeconomic disadvantage and unhealthy eating
      behaviours among adolescents are well established. Little is known about
      strategies that might support healthy eating among this target group. This study
      aimed to identify potential strategies and preferred dissemination methods that
      could be employed in nutrition promotion initiatives focussed on improving eating
      behaviours among socioeconomically disadvantaged adolescents. METHODS: Semi
      structured interviews were conducted in 2011 among 22 adolescents (12-15 years)
      recruited from secondary schools in disadvantaged neighbourhoods in Victoria,
      Australia. RESULTS: Strategies suggested by adolescents to support healthy eating
      included increasing awareness about healthy eating; greater cooking involvement;
      greater parental and peer support; frequent family meal participation; greater
      parental and peer role-modelling of healthy eating; increased availability of
      healthy foods and decreased availability of unhealthy foods in homes and schools.
      Adolescents preferred electronic media, adolescent-specific recipe books, and
      school-based methods for distributing nutrition promotion messages and
      strategies. CONCLUSIONS: A number of suggested strategies and methods identified
      in the present investigation have been employed with success in previous
      nutrition promotion interventions targeting socioeconomically disadvantaged
      adolescents. The present study also contributes novel insights into potential
      strategies and methods that could be employed in initiatives aiming to improve
      eating behaviours in this vulnerable group, and particularly highlights the
      importance of incorporating strategies involving parents and modifying the home
      food environment.

PMID- 25986469
TI  - Electric field control of proton-transfer molecular switching: molecular dynamics
      study on salicylidene aniline.
AB  - In this letter, we propose a novel, ultrafast, efficient molecular switch whose
      switching mechanism involves the electric field-driven intramolecular proton
      transfer. By means of ab initio quantum chemical calculations and on-the-fly
      dynamics simulations, we examine the switching performance of an isolated
      salicylidene aniline molecule and analyze the perspectives of its possible use as
      an electric field-controlled molecular electronics unit. 

PMID- 25986468
TI  - Predicting body composition using foot-to-foot bioelectrical impedance analysis
      in healthy Asian individuals.
AB  - BACKGROUND: The objectives of this study were to develop a regression model for
      predicting fat-free mass (FFM) in a population of healthy Taiwanese individuals
      using standing foot-to-foot bioelectrical impedance analysis (BIA) and to test
      the model's performance in predicting FFM with different body fat percentages
      (BF%). METHODS: We used dual-energy X-ray absorptiometry (DXA) to measure the FFM
      of 554 healthy Asian subjects (age, 16-75 y; body mass index, 15.8-43.1 kg/m(2)).
      We also evaluated the validity of the developed multivariate model using a double
      cross-validation technique and assessed the accuracy of the model in an all
      subjects sample and subgroup samples with different body fat levels. RESULTS:
      Predictors in the all-subjects multivariate model included height(2)/impedance,
      weight, year, and sex (FFM = 13.055 + 0.204 weight + 0.394 height(2)/Impedance -
      0.136 age + 8.125 sex (sex: Female = 0, Male = 1), r(2) = 0.92, standard error of
      the estimate = 3.17 kg). The correlation coefficients between predictive FFM by
      BIA (FFMBIA) and DXA-measured FFM (FFMDXA) in female subjects with a total
      subjects BF%DXA of <20 %, 20 %-30 %, 30 %-40 % and >40 % were r = 0.87, 0.90,
      0.91, 0.89, and 0.94, respectively, with bias +/- 2SD of 0.0 +/- 3.0 kg, -2.6 +/-
      1.7 kg, -1.5 +/- 2.8 kg, 0.5 +/- 2.7 kg, and 2.0 +/- 2.9 kg, respectively. The
      correlation coefficients between FFMBIA and FFMDXA in male subjects with a total
      subjects BF%DXA of <10 %, 10 %-20 %, 20 %-30 %, and >30 % were r = 0.89, 0.89,
      0.90, 0.93, and 0.91, respectively, with bias +/- 2SD of 0.0 +/- 3.2 kg, -2.3 +/-
      2.5 kg, -0.5 +/- 3.2 kg, 0.4 +/- 3.1 kg, and 2.1 +/- 3.2 kg, respectively.
      CONCLUSIONS: The standing foot-to-foot BIA method developed in this study can
      accurately predict FFM in healthy Asian individuals with different levels of body
      fat.

PMID- 25986470
TI  - Applying Multiple Criteria Decision Analysis to Comparative Benefit-Risk
      Assessment: Choosing among Statins in Primary Prevention.
AB  - Decision makers in different health care settings need to weigh the benefits and
      harms of alternative treatment strategies. Such health care decisions include
      marketing authorization by regulatory agencies, practice guideline formulation by
      clinical groups, and treatment selection by prescribers and patients in clinical
      practice. Multiple criteria decision analysis (MCDA) is a family of formal
      methods that help make explicit the tradeoffs that decision makers accept between
      the benefit and risk outcomes of different treatment options. Despite the recent
      interest in MCDA, certain methodological aspects are poorly understood. This
      paper presents 7 guidelines for applying MCDA in benefit-risk assessment and
      illustrates their use in the selection of a statin drug for the primary
      prevention of cardiovascular disease. We provide guidance on the key
      methodological issues of how to define the decision problem, how to select a set
      of nonoverlapping evaluation criteria, how to synthesize and summarize the
      evidence, how to translate relative measures to absolute ones that permit
      comparisons between the criteria, how to define suitable scale ranges, how to
      elicit partial preference information from the decision makers, and how to
      incorporate uncertainty in the analysis. Our example on statins indicates that
      fluvastatin is likely to be the most preferred drug by our decision maker and
      that this result is insensitive to the amount of preference information
      incorporated in the analysis.

PMID- 25986471
TI  - Interpretation of the Expected Value of Perfect Information and Research
      Recommendations: A Systematic Review and Empirical Investigation.
AB  - BACKGROUND: Expected value of perfect information (EVPI) calculations are
      increasingly performed to guide and underpin research recommendations. An EVPI
      value that exceeds the estimated cost of research forms a necessary (although not
      sufficient) condition for further research to be considered worthwhile. However,
      it is unclear what factors affect researchers' recommendations and whether there
      is a notional threshold of positive returns below which research is not
      recommended. The objectives of this study were to explore whether EVPI and other
      factors have a bearing on research recommendations and to assess whether there
      exists a threshold EVPI below which research is typically not recommended.
      METHODS: A systematic literature review was undertaken to identify applied EVPI
      calculations in the health care field. Study characteristics were extracted,
      including funder, location, disease group, publication year, primary language,
      and outcome measure. Population EVPI values and willingness-to-pay thresholds
      were also extracted alongside verbatim text excerpts describing the authors'
      research recommendations. Recommendations were classified according to whether
      further research was recommended (a positive recommendation) or not (negative).
      Factors affecting the likelihood of a positive recommendation were examined
      statistically using logistic regression and visually by plotting the results in
      graphs. RESULTS AND CONCLUSIONS: Eighty-six articles were included, of which 13
      suggested no further research, 66 recommended further research, and 7 gave no
      recommendation. EVPI appears to be a key driver of researchers' recommendations
      for further research. Disease area, funder, study location, publication year, and
      outcome may have a bearing on recommendations, although none of these factors
      reached statistical significance. A threshold EVPI value below which research is
      typically not recommended was found at around L 1.48 million.

PMID- 25986472
TI  - An Approach to Assess Generalizability in Comparative Effectiveness Research: A
      Case Study of the Whole Systems Demonstrator Cluster Randomized Trial Comparing
      Telehealth with Usual Care for Patients with Chronic Health Conditions.
AB  - BACKGROUND: Policy makers require estimates of comparative effectiveness that
      apply to the population of interest, but there has been little research on
      quantitative approaches to assess and extend the generalizability of randomized
      controlled trial (RCT)-based evaluations. We illustrate an approach using
      observational data. METHODS: Our example is the Whole Systems Demonstrator (WSD)
      trial, in which 3230 adults with chronic conditions were assigned to receive
      telehealth or usual care. First, we used novel placebo tests to assess whether
      outcomes were similar between the RCT control group and a matched subset of
      nonparticipants who received usual care. We matched on 65 baseline variables
      obtained from the electronic medical record. Second, we conducted sensitivity
      analysis to consider whether the estimates of treatment effectiveness were robust
      to alternative assumptions about whether "usual care" is defined by the RCT
      control group or nonparticipants. Thus, we provided alternative estimates of
      comparative effectiveness by contrasting the outcomes of the RCT telehealth group
      and matched nonparticipants. RESULTS: For some endpoints, such as the number of
      outpatient attendances, the placebo tests passed, and the effectiveness estimates
      were robust to the choice of comparison group. However, for other endpoints, such
      as emergency admissions, the placebo tests failed and the estimates of treatment
      effect differed markedly according to whether telehealth patients were compared
      with RCT controls or matched nonparticipants. CONCLUSIONS: The proposed placebo
      tests indicate those cases when estimates from RCTs do not generalize to routine
      clinical practice and motivate complementary estimates of comparative
      effectiveness that use observational data. Future RCTs are recommended to
      incorporate these placebo tests and the accompanying sensitivity analyses to
      enhance their relevance to policy making.

PMID- 25986474
TI  - Fabrication of CeO2 nanotube supported Pt catalyst encapsulated with silica for
      high and stable performance.
AB  - This communication describes the fabrication of Pt/CeO2 nanotube@SiO2 core-shell
      catalysts applied to highly efficient water-gas shift reaction, where the initial
      CO conversion is 30.2% at 250  degrees C. Pt/CeO2 nanotube@SiO2 core-shell
      catalysts show outstanding thermal stability, even after accelerated aging under
      reaction conditions at 450  degrees C for 6 h, and the morphology is also
      unchanged after thermal treatment at 800  degrees C. 

PMID- 25986475
TI  - Serum C-reactive protein and overall survival of patients with osteosarcoma.
AB  - Increased level of serum C-reactive protein (CRP) has been identified as an
      important prognostic factor in several types of cancers. However, the prognostic
      significance of serum CRP levels in patients with osteosarcoma was still unclear.
      A retrospective cohort study of 85 patients was performed to assess the
      prognostic significance of serum CRP level in osteosarcoma. Both log-rank test
      and multivariable analysis by Cox regression model were used to assess the impact
      of serum CRP levels on the overall survival in patients with osteosarcoma. Among
      those 85 patients, 28 (32.9 %) had high serum CRP level (>1 mg/dL), while the
      other 57 (67.1 %) patients had normal serum CRP level (<= 1 mg/dL). There was no
      obvious difference in the baseline characteristics between high CRP group and
      normal CRP group. Kaplan-Meier product-limit method showed that patients with
      high serum CRP levels had significantly poorer overall survival than those
      patients with normal serum CRP levels (log-rank test P = 0.0008). Multivariable
      analysis by Cox regression model further showed that high serum CRP level was an
      independent predictor of poor overall survival (hazard ratio [HR] = 2.39; 95 %
      confidence interval [95 % CI] 1.22-4.67, P = 0.01). Thus, serum CRP level has an
      important prognostic significance in patients with osteosarcoma, and high CRP
      level is associated with worse overall survival.

PMID- 25986473
TI  - Induction of autophagy is a key component of all-trans-retinoic acid-induced
      differentiation in leukemia cells and a potential target for pharmacologic
      modulation.
AB  - Acute myeloid leukemia (AML) is characterized by the accumulation of immature
      blood cell precursors in the bone marrow. Pharmacologically overcoming the
      differentiation block in this condition is an attractive therapeutic avenue,
      which has achieved success only in a subtype of AML, acute promyelocytic leukemia
      (APL). Attempts to emulate this success in other AML subtypes have thus far been
      unsuccessful. Autophagy is a conserved protein degradation pathway with important
      roles in mammalian cell differentiation, particularly within the hematopoietic
      system. In the study described here, we investigated the functional importance of
      autophagy in APL cell differentiation. We found that autophagy is increased
      during all-trans-retinoic acid (ATRA)-induced granulocytic differentiation of the
      APL cell line NB4 and that this is associated with increased expression of LC3II
      and GATE-16 proteins involved in autophagosome formation. Autophagy inhibition,
      using either drugs (chloroquine/3-methyladenine) or short-hairpin RNA targeting
      the essential autophagy gene ATG7, attenuates myeloid differentiation.
      Importantly, we found that enhancing autophagy promotes ATRA-induced granulocytic
      differentiation of an ATRA-resistant derivative of the non-APL AML HL60 cell line
      (HL60-Diff-R). These data support the development of strategies to stimulate
      autophagy as a novel approach to promote differentiation in AML. 

PMID- 25986476
TI  - The daily cost of ICU patients: A micro-costing study in 23 French Intensive Care
      Units.
AB  - OBJECTIVES: To estimate the daily cost of intensive care unit (ICU) stays via
      micro-costing. METHODS: A multicentre, prospective, observational, cost analysis
      study was carried out among 21 out of 23 French ICUs randomly selected from
      French National Hospitals. Each ICU randomly enrolled 5 admitted adult patients
      with a simplified acute physiology II score >= 15 and with at least one major
      intensive care medical procedure. All health-care human resources used by each
      patient over a 24-hour period were recorded, as well as all medications,
      laboratory analyses, investigations, tests, consumables and administrative
      expenses. All resource costs were estimated from the hospital's perspective
      (reference year 2009) based on unitary cost data. RESULTS: One hundred and four
      patients were included (mean age: 62.3 +/- 14.9 years, mean SAPS II: 51.5 +/-
      16.1, mean SOFA on the study day: 6.9 +/- 4.3). Over 24 hours, 29 to 186
      interventions per patient were performed by different caregivers, leading to a
      mean total time spent for patient care of 13:32 +/- 05:00 h. The total daily cost
      per patient was ? 1425 +/- ? 520 (95% CI = ? 1323 to ? 1526). ICU human resources
      represented 43% of total daily cost. Patient-dependent expenses (? 842 +/- ? 521)
      represented 59% of the total daily cost. The total daily cost was correlated with
      the daily SOFA score (r = 0.271, P = 0.006) and the bedside-time given by
      caregivers (r = 0.716, P < 0.0001). CONCLUSION: The average cost of one day of
      ICU care in French National Hospitals is strongly correlated with the duration of
      bedside-care carried out by human resources.

PMID- 25986477
TI  - Erratum: Association between knowledge of caries preventive practices, preventive
      oral health habits of parents and children and caries experience in children
      resident in sub-urban Nigeria.

PMID- 25986478
TI  - Comparing the effectiveness of capecitabine versus 5-fluorouracil/leucovorin
      therapy for elderly Taiwanese stage III colorectal cancer patients based on
      quality-of-life measures (QLQ-C30 and QLQ-CR38) and a new cost assessment tool.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related deaths
      in developed countries and its incidence increases with age. Intravenous
      administration of bolus 5-fluorouracil (5-FU) and leucovorin (LV) has been a
      standard treatment regime for stage III CRC. However, patients generally prefer
      oral therapy such as Capecitabine. Studies showed that combination of oxaliplatin
      and capecitabine demonstrated efficacy and safety on par with treatment involving
      various 5-FU/LV-based regimens in elderly patients as they are in younger ones.
      However, little is known regarding the cost of adjuvant therapy or the effect of
      therapy on HRQoL. Thus the aims of this study were to evaluate the influence of
      different adjuvant care for stage III CRC on the HRQoL of elderly patients and to
      compare the economic costs associated with capecitabine-based and 5-FU/LV-based
      adjuvant treatments from a societal perspective in Taiwan. METHODS: A
      prospective, open-label, observational, multicenter study involving 123 patients
      aged 70 and over from 11 different centers was conducted between July 2008 and
      July 2011 in Taiwan. The adjusted monthly costs per patient and HRQoL were
      evaluated from individual-level data. The HRQoL of patients was assessed before
      and after adjuvant treatment. Direct and indirect costs of adjuvant treatment
      were estimated from a number of sources, and QoL scores were compared between
      groups. RESULTS: After correcting for baseline characteristics of patients, no
      significant differences were observed in the global HRQoL scores between
      treatment groups during the study period. According to QLQ-CR38 results,
      capecitabine-based therapy appeared to alleviate problems related to defecation
      (4.54 vs. 8.5; P = 0.011); however, micturition problems increased (9.27 vs.
      7.51; P = 0.04), compared with 5-FU/LV-based treatment. The adjusted monthly
      treatment cost per patient was NT$27,300 for capecitabine-based treatment and
      NT$53,671 for 5-FU/LV-based treatment. The total cost of 5-FU/LV-based treatment
      was 59 % greater than that of capecitabine-based treatment. CONCLUSIONS:
      Analyzing from the societal perspective in Taiwan, capecitabine-based therapy
      incurred lower treatment costs than 5-FU/LV-based therapy and did not jeopardize
      HRQoL. Therefore, capecitabine, with or without oxaliplatin, could be considered
      as an alternative treatment option for elderly patients with stage III CRC.

PMID- 25986479
TI  - External validation of the PROFUND index in polypathological patients from
      internal medicine and acute geriatrics departments in Aragon.
AB  - The objective of the study was to validate externally and prospectively the
      PROFUND index to predict survival of polypathological patients after a year. An
      observational, prospective and multicenter study was performed. Polypathological
      patients admitted to an internal medicine or geriatrics department and attended
      by investigators consecutively between March 1 and June 30, 2011 were included.
      Data concerning age, gender, comorbidity, Barthel and Lawton-Brody indexes,
      Pfeiffer questionnaire, socio-familial Gijon scale, delirium, number of drugs and
      number of admissions during the previous year were gathered for each patient. The
      PROFUND index was calculated. The follow-up lasted 1 year. A Cox proportional
      regression model was calculated, and was used to analyze the association of the
      variables to mortality and C-statistic. 465 polypathological patients, 333 from
      internal medicine and 132 from geriatrics, were included. One-year mortality is
      associated with age [hazard ratio (HR) 1.52 95 % CI 1.04-2.12; p = 0.01],
      presence of neoplasia [HR 2.68 95 % CI 1.71-4.18; p = 0.0001] and dependence for
      basic activities of daily living [HR 2.34 95 % CI 1.61-3.40; p = 0.0009]. In
      predicting mortality, the PROFUND index shows good discrimination in patients
      from internal medicine (C-statistics 0.725 95 % CI 0.670-0.781), but a poor one
      in those from geriatrics (0.546 95 % CI 0.448-0.644). The PROFUND index is a
      reliable tool for predicting mortality in internal medicine PP patients.

PMID- 25986480
TI  - Relation between admission serum potassium levels and long-term mortality in
      acute coronary syndrome.
AB  - Serum potassium homeostasis play an important role in myocardial function, but
      the impact of serum potassium levels on long-term mortality has not been well
      evaluated. In the current study, we investigated patients with acute coronary
      syndrome (ACS) and analyzed the relationship between admission serum potassium
      levels and long-term mortality. Between July 2008 and September 2012, 2369
      patients with ACS that was confirmed by coronary angiography were enrolled in
      this study and completed the follow-up. The serum potassium level was evaluated
      within first 24 h after admission. The primary outcome in this study was all
      cause mortality. Patients were categorized into five groups to determine the
      relation between admission serum potassium levels and long-term mortality: < 3.5,
      3.5 to < 4.0, 4.0 to < 4.5, 4.5 to < 5.0, and > 5 mEq/L. There was a U-shaped
      relationship between admission serum potassium levels and long-term mortality
      that persisted after multivariable adjustment. The mortality risk was lowest in
      the group of patients with potassium levels of 3.5 to < 4.0 mEq/L, whereas
      mortality was higher in patients with potassium levels > 4.5 [hazard ratio (HR)
      1.62, 95 % confidence interval (CI) 0.90 to 2.93 and HR 1.55, 95 % CI 0.54 to
      4.49, for patients with potassium levels of 4.5 to < 5.0 mEq/L and >= 5.0 mEq/L,
      respectively] or < 3.5 mEq/L (HR 2.14, 95 % CI 1.28 to 3.59). There was a U
      shaped relationship between admission serum potassium levels and long-term
      mortality for ACS patients; in particular, among the examined patients, the
      lowest mortality was observed in those with admission serum potassium levels of
      between 3.5 and < 4.5 mEq/L compared with those who had higher or lower potassium
      levels.

PMID- 25986481
TI  - Anemia and splenomegaly: what lies behind?

PMID- 25986482
TI  - Attitudes and preferences for the clinical management of patients with
      hypertension and hypertension with chronic obstructive pulmonary disease in
      Italy: main results of a survey questionnaire.
AB  - Hypertension treatment and control represent a clinical challenge, particularly
      in case of concomitant risk factors and comorbidities, including chronic
      obstructive pulmonary disease (COPD). To evaluate attitudes and preferences for
      the clinical management of hypertension and hypertension associated with COPD by
      a large community sample of physicians in Italy. A predefined 18-item survey
      questionnaire was anonymously administered to both specialised physicians (SPs)
      and general practitioners (GPs), who have been included in an educational
      programme, performed between January and June 2014. A total of 1181 physicians
      (767 males, mean age 55.8 +/- 7.3 years, average age of medical activity 27.6 +/-
      8.3 years), among whom 64 (5.4 %) SPs and 1117 (94.6 %) GPs, provided 21,809
      valid answers to the survey questionnaire. Concomitant presence of hypertension
      and COPD was frequently associated (21-40 %) with hypertension-related organ
      damage and comorbidities. Concomitant presence of hypertension and COPD was able
      to affect physicians' ability to achieve the recommended therapeutic targets. To
      achieve the recommended BP goals, ACE inhibitors or ARBs were considered the most
      effective antihypertensive strategies, both in monotherapies and in combination
      therapies with either diuretics or calcium-channel blockers. This observational,
      cross-sectional survey provides useful information on physicians' attitudes and
      preferences for the clinical management of patients with hypertension and
      hypertension associated with COPD.

PMID- 25986483
TI  - A candidate gene study reveals association between a variant of the Peroxisome
      Proliferator-Activated Receptor Gamma (PPAR-gamma) gene and systemic sclerosis.
AB  - INTRODUCTION: The multifunctional nuclear receptor peroxisome proliferator
      activated receptor gamma (PPAR-gamma) has potent anti-fibrotic effects, and its
      expression and activity are impaired in patients with systemic sclerosis (SSc).
      We investigated PPAR-gamma gene (PPARG) single nucleotide polymorphisms (SNPs)
      associated with SSc. METHODS: Tag SNPs spanning PPARG were genotyped in a
      European ancestry US discovery cohort comprising 152 SSc patients and 450
      controls, with replication of our top signal in a European cohort (1031 SSc
      patients and 1014 controls from France). Clinical parameters and disease severity
      were analyzed to evaluate clinical associations with PPARG variants. RESULTS: In
      the discovery cohort, a single PPARG intronic SNP (rs10865710) was associated
      with SSc (p=0.010; odds ratio=1.52 per C allele, 95% confidence interval 1.10
      2.08). This association was replicated in the French validation cohort (p=0.052;
      odds ratio=1.16 per C allele, 95% confidence interval 1.00-1.35). Meta-analysis
      of both cohorts indicated stronger evidence for association (p=0.002; odds
      ratio=1.22 per C allele, 95% confidence interval 1.07-1.40). The rs10865710 C
      allele was also associated with pulmonary arterial hypertension in the French SSc
      cohort (p=0.002; odds ratio=2.33 per C allele, 95% confidence interval 1.34
      4.03). CONCLUSIONS: A PPARG variant is associated with susceptibility to SSc,
      consistent with a role of PPAR-gamma in the pathogenesis of SSc.

PMID- 25986484
TI  - Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in
      a rat stroke model.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is an autoimmune disorder of the central
      nervous system, which is characterized by autoantibodies directed against the
      water channel aquaporin-4 (AQP4). As one of the main water regulators in the
      central nervous system, APQ4 is supposed to be involved in the dynamics of brain
      edema. Cerebral edema seriously affects clinical outcome after ischemic stroke;
      we therefore aimed to investigate whether NMO-antibodies may exert the same
      functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke.
      METHODS: Sixteen male Wistar rats were randomized into two groups twice receiving
      either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30
      minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted
      MRI was carried out 24 hours after MCAO. RESULTS: MRI-examination showed a
      significant increase of infarct size in relation to the cerebral hemisphere
      volume with NMO-IgG treated animals (27.1% +/- 11.1% vs. 14.3% +/- 7.2%; p <
      0.05) when corrected for the space-occupying effect of vasogenic edema formation
      and similar results without edema correction (34.4% +/- 16.4% vs. 17.5% +/- 9.3%;
      p < 0.05). Furthermore, T2-RT revealed a significant increase in cortical brain
      water content of the treatment group (19.5 ms +/- 9.7 ms vs. 9.2 ms +/- 5.2 ms; p
      < 0.05). CONCLUSIONS: These results support the functional impact of NMO
      antibodies and also offer an in-vivo-applicable animal model to investigate the
      properties of AQP4 in ischemic stroke.

PMID- 25986485
TI  - Poor accuracy of plain radiographic measurements of prosthetic migration and
      alignment in total ankle replacement.
AB  - BACKGROUND: The rotational position of the leg substantially influences
      measurements in ankle radiographs after total ankle replacement (TAR). The aim of
      our study was to further specify the influence of different projections on
      radiographic parameters used to assess component position after TAR. METHODS: The
      effect of varying degrees of internal rotation, flexion, and ab-/adduction on
      reference lines in anteroposterior and lateral ankle radiographs was investigated
      in a cadaveric TAR model. Observed variations were then compared with those found
      in 34 consecutive patients that received a HINTEGRA total ankle prosthesis in our
      department. RESULTS: A change of rotation of 20 degrees  resulted in a variation
      of measured reference lines of more than 1.3 cm in anteroposterior radiographs
      and more than 1 cm in lateral radiographs in our experimental setting. Even
      higher intraindividual changes of up to 1.4 cm were observed in our in vivo
      series. CONCLUSIONS: The findings suggest that rotational position of the leg
      highly influences measurements in ankle radiographs after TAR. It further raises
      the question, if previously described radiographic parameters do provide accurate
      information for the outcome after TAR in clinical routine as suggested in
      literature.

PMID- 25986486
TI  - Electron microscopic examination of podosomes induced by phorbol 12, 13
      dibutyrate on the surface of A7r5 cells.
AB  - The role of myosin light chain kinase (MLCK) in inducing podosomes was examined
      by confocal and electron microscopy. Removal of myosin from the actin core of
      podosomes using blebbistatin, a myosin inhibitor, resulted in the formation of
      smaller podosomes. Downregulation of MLCK by the transfection of MLCK small
      interfering RNA (siRNA) led to the failure of podosome formation. However, ML-7,
      an inhibitor of the kinase activity of MLCK, failed to inhibit podosome
      formation. Based on our previous report (Thatcher et al. J.Pharm.Sci. 116 116
      127, 2011), we outlined the important role of the actin-binding activity of MLCK
      in producing smaller podosomes.

PMID- 25986487
TI  - Corrigendum to "Chronic administration of nicotine-free cigarette smoke extract
      impaired endothelium-dependent vascular relaxation in rats via increased vascular
      oxidative stress" [J Pharmacol Sci 118 (2012) 206-214].

PMID- 25986489
TI  - [Necrosis of maxilla secondary to purpura fulminans. A case report].
AB  - Purpura fulminans in infants is a rare, life-threatening condition mostly due to
      Neisseria meningitides. The condition is often fatal unless there is early
      recognition of the clinical symptoms, prompt diagnosis, and judicious replacement
      therapy. We observed a case of maxilla necrosis in a 5-month-old infant due to
      purpura fulminans. An acute necrotic process affecting the maxilla with
      denudation of bone and spontaneous exfoliation of teeth was noted. After 2
      months, the patient was free of symptoms. To our knowledge, this is the first
      case report of necrosis of the maxilla secondary to a purpura fulminans. Prompt
      diagnosis and prompt medical intervention are necessary to avoid such
      complications. 

PMID- 25986488
TI  - Protective role of p120-catenin in maintaining the integrity of adherens and
      tight junctions in ventilator-induced lung injury.
AB  - BACKGROUND: Ventilator-induced lung injury (VILI) is one of the most common
      complications for patients with acute lung injury (ALI) or acute respiratory
      distress syndrome (ARDS). Although p120 is an important protein in the regulation
      of cell junctions, further mechanisms should be explored for prevention and
      treatment of VILI. METHODS: Mouse lung epithelial cells (MLE-12), which were
      transfected with p120 small interfering (si)RNA, p120 cDNA, wild-type E-cadherin
      juxtamembrane domain or a K83R mutant juxtamembrane domain (K83R-JMD), were
      subjected to 20% cyclic stretches for 2 or 4 h. Furthermore, MLE-12 cells and
      mice, which were pretreated with the c-Src inhibitor PP2 or RhoA inhibitor
      Y27632, underwent 20% cyclic stretches or mechanical stretching, respectively.
      Moreover, wild-type C57BL/6 mice were transfected with p120 siRNA-liposome
      complexes before mechanical ventilation. Cell lysates and lung tissues were then
      analyzed to detect lung injury. RESULTS: cyclic stretches of 20% actived c-Src,
      which induced degradation of E-cadherin, p120 and occludin. However, loss of p120
      increased the degradation and endocytosis of E-cadherin. Immunoprecipitation and
      Immunofluorescence results showed a decrease in the association between p120 and
      E-cadherin, while gap formation increased in p120 siRNA and K83R-JMD groups after
      20% cyclic stretches. Loss of p120 also reduced the occludin level and decreased
      the association of occludin and ZO-1 by enhancing RhoA activity. However, the
      altered levels of occludin and E-cadherin were reversed by PP2 or Y27632
      treatments compared with the cyclic stretch group. Consistently, the expression,
      redistribution and disassociation of junction proteins were all restored in the
      p120 overexpression group after 20% cyclic stretches. Moreover, the role of p120
      in VILI was confirmed by increased wet/dry weigh ratio and enhanced production of
      cytokines (tumor necrosis factor-alpha and interleukin-six) in p120-depleted mice
      under mechanical ventilation. CONCLUSIONS: p120 protected against VILI by
      regulating both adherens and tight junctions. p120 inhibited E-cadherin
      endocytosis by increasing the association between p120 and juxtamembrane domain
      of E-cadherin. Furthermore, p120 reduced the degradation of occludin by
      inhibiting RhoA activity. These findings illustrated further mechanisms of p120
      in the prevention of VILI, especially for patients with ALI or ARDS.

PMID- 25986490
TI  - Conserved water molecules in bacterial serine hydroxymethyltransferases.
AB  - Water molecules occurring in the interior of protein structures often are endowed
      with key structural and functional roles. We report the results of a systematic
      analysis of conserved water molecules in bacterial serine
      hydroxymethyltransferases (SHMTs). SHMTs are an important group of pyridoxal-5'
      phosphate-dependent enzymes that catalyze the reversible conversion of l-serine
      and tetrahydropteroylglutamate to glycine and 5,10
      methylenetetrahydropteroylglutamate. The approach utilized in this study relies
      on two programs, ProACT2 and WatCH. The first software is able to categorize
      water molecules in a protein crystallographic structure as buried, positioned in
      clefts or at the surface. The other program finds, in a set of superposed
      homologous proteins, water molecules that occur approximately in equivalent
      position in each of the considered structures. These groups of molecules are
      referred to as 'clusters' and represent structurally conserved water molecules.
      Several conserved clusters of buried or cleft water molecules were found in the
      set of 11 bacterial SHMTs we took into account for this work. The majority of
      these clusters were not described previously. Possible structural and functional
      roles for the conserved water molecules are envisaged. This work provides a map
      of the conserved water molecules helpful for deciphering SHMT mechanism and for
      rational design of molecular engineering experiments. 

PMID- 25986491
TI  - Adding a new dimension to our understanding of continuous-flow physiology.

PMID- 25986492
TI  - Simulation-based learning of transesophageal echocardiography in cardiothoracic
      surgical trainees: A prospective, randomized study.
AB  - OBJECTIVES: The Intercollegiate Surgical Curriculum now recommends that cardiac
      surgical trainees should be able to understand and interpret transesophageal
      echocardiography images. However, cardiac surgical trainees receive limited
      formal transesophageal echocardiography training. The objective of this study was
      to assess the impact of simulation-based teaching versus more traditional
      operating room teaching on transesophageal echocardiography knowledge in cardiac
      surgical trainees. METHODS: A total of 25 cardiac surgical trainees with no
      formal transesophageal echocardiography learning experience were randomly
      assigned by computer to a study group receiving simulation-based transesophageal
      echocardiography teaching via the Heartworks (Inventive Medical, London, UK)
      simulator (n = 12) or a control group receiving transesophageal echocardiography
      teaching during elective cardiac surgery (n = 13). Each subject undertook a video
      based test composed of 20 multiple choice questions on standard transesophageal
      echocardiography views before and after teaching. RESULTS: There was no
      significant difference in the pretest scores between the 2 groups (P = .89).
      After transesophageal echocardiography teaching, subjects within each group
      demonstrated a statistically significant improvement in transesophageal
      echocardiography knowledge. Although the subjects within the simulation group
      outperformed their counterparts in the operating room teaching group in the post
      test scores, this difference was not significant (P = .14). CONCLUSIONS: Despite
      the familiarity with transesophageal echocardiography images during surgery,
      subjects in the simulation group performed at least as well as those in the
      operating room group. Surgical trainees will benefit from formal transesophageal
      echocardiography teaching incorporated into their training via either learning
      method.

PMID- 25986493
TI  - Intrathoracic anastomotic leakage after gastroesophageal cancer resection is
      associated with increased risk of recurrence.
AB  - OBJECTIVE: Intrathoracic anastomotic leakage after intended curative resection
      for cancer in the esophagus or gastroesophageal junction has a negative impact on
      long-term survival. The aim of this study was to investigate whether an
      anastomotic leakage was associated with an increased recurrence rate. METHODS:
      This nationwide study included consecutively collected data on patients
      undergoing curative surgical resection with intrathoracic anastomosis, alive 8
      weeks postoperatively, between 2003 and 2011. Patients with incomplete resection,
      or metastatic disease intraoperatively, were excluded. Only biopsy-proven
      recurrences were accepted. RESULTS: In total, 1085 patients were included. The
      frequency of anastomotic leakage was 8.6%. The median follow-up time was 29
      months (interquartile range [IQR]: 13-58 months). Overall, 369 (34%) patients had
      disease recurrence, of which 346 patients died of recurrent gastroesophageal
      carcinoma. Twenty-three patients were alive with recurrence at the censoring
      date. In the study period, 333 patients died without signs of recurrent disease.
      The overall median time to recurrence was 66 weeks (IQR: 38-109 weeks). Distant
      metastases were found in 267 (25%), and local disease recurrence in 102 (9%)
      patients. Overall, 5-year disease-free survival in patients with leakage was 27%,
      versus 39% in those without leakage (P = .017). Anastomotic leakage was
      independently associated with higher risk of recurrence (hazard ratio [HR] =
      1.63; 95% confidence interval [CI]: 1.17-2.29, P = .004) and all-cause mortality
      (HR = 1.57; 95% CI: 1.23-2.05, P < .0001). CONCLUSIONS: Intrathoracic anastomotic
      leakage increased the risk of recurrence in patients who underwent curative
      gastroesophageal cancer resection.

PMID- 25986494
TI  - Is there an outcome penalty linked to guideline-based indications for valvular
      surgery? Early and long-term analysis of patients with organic mitral
      regurgitation.
AB  - OBJECTIVE: The timing of surgical correction of mitral regurgitation remains
      controversial. A major source of dispute regards the potential short- and long
      term postoperative outcome penalty associated with the type of guideline-based
      indication for surgery. METHODS: Between 1990 and 2000, 1512 patients (aged 64 +/
      14 years, mitral prolapse in 89%, valve repair in 88%) underwent surgical
      correction of pure organic mitral regurgitation. Patients were stratified
      according to surgical indication into class I triggers (ClassI-T: heart failure
      symptoms, ejection fraction <60%, end-systolic diameter >=40 mm, n = 794), class
      II triggers based on clinical complications (ClassII-CompT: atrial fibrillation
      or pulmonary hypertension, n = 195), or early class II triggers based on a
      combination of severe mitral regurgitation and high probability of valve repair
      (ClassII-EarlyT: n = 523). RESULTS: Operative mortality was highest with ClassI-T
      (1.1% vs 0% and 0%, P = .016). Long-term survival was lower with ClassI-T (15
      year 42% +/- 2%; adjusted hazard ratio [HR], 1.89; 95% confidence interval [CI],
      1.53-2.34; P < .0001) and ClassII-CompT (15-year 53% +/- 4%, adjusted HR, 1.39;
      95% CI, 1.04-1.84; P = .027) versus ClassII-EarlyT (15-year 70% +/- 3%, P <
      .0001). Postoperative excess mortality with ClassI-T and ClassII-CompT was
      confirmed by age stratification, inverse probability weighting, and expected
      survival adjustment. Excess postoperative heart failure was high with ClassI-T
      (adjusted HR, 2.49; 95% CI, 1.82-3.47; P < .0001) and ClassII-CompT (adjusted HR,
      1.98; 95% CI, 1.30-3.00; P = .002). CONCLUSIONS: The type of guideline-based
      indication for surgical correction of organic mitral regurgitation is associated
      with profound outcome consequences on long-term postoperative mortality and heart
      failure, despite low operative risk and high repair rates. Conversely, surgical
      correction of severe mitral regurgitation based on high probability of repair
      (ClassII-EarlyT) is associated with improved survival and low heart failure risk
      and should be the preferred strategy in valve centers offering low operative risk
      and high repair rates.

PMID- 25986495
TI  - Risk factors for acute kidney injury after surgery of the thoracic aorta using
      antegrade selective cerebral perfusion and moderate hypothermia.
AB  - BACKGROUND: The development of acute kidney injury (AKI) in cardiac surgery is
      associated with increased morbidity and mortality. The aim of the study was to
      assess the incidence and risk factors for AKI after thoracic aorta surgery, using
      antegrade selective cerebral perfusion (ASCP) and moderate hypothermia. METHODS:
      We reviewed 641 patients undergoing thoracic aortic surgery, using ASCP and
      moderate hypothermia, from November 1996 to December 2012. Patient preoperative,
      intraoperative, and postoperative variables were evaluated for association with
      AKI with logistic regression analysis. Models including all variables and models,
      after the sequential removal of postoperative, and both postoperative and
      intraoperative variables, were assessed using receiver operating characteristic
      analysis. RESULTS: The mean age of the patients was 62.9 years, and 194 patients
      (30%) were women. The overall incidence of AKI was 19.0%. In-hospital mortality
      was significantly higher in the AKI group (33.6% vs 6.7%; P < .001). Logistic
      regression analysis identified 8 predictors of AKI: 4 of them were preoperative
      (priority, diabetes, preoperative glomerular filtration rate, and weight); 2
      intraoperative (mitral valve and aortic valve replacement); and 2 postoperative
      (overall neurologic complication and reoperation for bleeding). Model
      discrimination performance improved from an area under the curve (AUC) of 0.737,
      for the model including only preoperative variables, to an AUC of 0.798 for the
      model including all variables (P = .012). CONCLUSIONS: The incidence of AKI after
      thoracic aorta surgery is fairly common, and its occurrence strongly affects
      outcomes. Preoperative renal status and preoperative conditions are the main
      influences on AKI development. Predictive models can be improved by adding
      intraoperative and postoperative variables.

PMID- 25986497
TI  - Time trends and gender differences in prevention guideline adherence and outcome
      after myocardial infarction: Data from the SWEDEHEART registry.
AB  - BACKGROUND: While secondary prevention improves prognosis after acute myocardial
      infarction (AMI), previous studies have suggested suboptimal guideline adherence,
      lack of improvement over time and gender differences. This study contributes
      contemporary data from a large national cohort. METHOD: We identified 51,620
      patients <75 years examined at two and/or twelve months post AMI in the Swedish
      Web-system for Enhancement and Development of Evidence-based care in Heart
      disease Evaluated According to Recommended Therapies (SWEDEHEART). Risk factor
      control and readmissions at one year were compared between the 2005 and 2012
      cohorts, and between genders. RESULTS: Lipid control (LDL-cholesterol <2.5
      mmol/L) improved from 67.9% to 71.1% (p = 0.016) over time, achieved by 67.9% vs
      63.3%, p < 0.001 of men vs women. Blood pressure control (<140 mmHg systolic)
      increased over time (59.1% vs 69.5%, p < 0.001 in 2005 and 2012 cohorts) and was
      better in men (66.4% vs 61.9%, p < 0.001). Smoking cessation rate was 55.6%
      without differences between genders or over time. Cardiac readmissions occurred
      in 18.2% of women and 15.5% of men, decreasing from 2005 to 2012 (20.8% vs
      14.9%). Adjusted odds ratio was 1.22 (95% CI 1.14-1.32) for women vs men and 0.94
      (95% CI 0.92-0.96) for the 2012 vs the 2005 cohort. CONCLUSIONS: Although this
      study compares favourably to previous studies of risk factor control post AMI,
      improvement over time was mainly seen regarding blood pressure, revealing
      substantial remaining preventive potential. The reasons for gender differences
      seen in risk factor control and readmissions require further analysis.

PMID- 25986498
TI  - Methods for Derivation of Multipotent Neural Crest Cells Derived from Human
      Pluripotent Stem Cells.
AB  - Multipotent, neural crest cells (NCCs) produce a wide range of cell types during
      embryonic development. This includes melanocytes, peripheral neurons, smooth
      muscle cells, osteocytes, chondrocytes, and adipocytes. The protocol described
      here allows for highly efficient differentiation of human pluripotent stem cells
      to a neural crest fate within 15 days. This is accomplished under feeder-free
      conditions, using chemically defined medium supplemented with two small molecule
      inhibitors that block glycogen synthase kinase 3 (GSK3) and bone morphogenic
      protein (BMP) signaling. This technology is well suited as a platform to
      understand in greater detail the pathogenesis of human disease associated with
      impaired neural crest development/migration. 

PMID- 25986499
TI  - Genome-wide activities of Polycomb complexes control pervasive transcription.
AB  - Polycomb group (PcG) complexes PRC1 and PRC2 are well known for silencing
      specific developmental genes. PRC2 is a methyltransferase targeting histone H3K27
      and producing H3K27me3, essential for stable silencing. Less well known but
      quantitatively much more important is the genome-wide role of PRC2 that
      dimethylates ~70% of total H3K27. We show that H3K27me2 occurs in inverse
      proportion to transcriptional activity in most non-PcG target genes and
      intergenic regions and is governed by opposing roaming activities of PRC2 and
      complexes containing the H3K27 demethylase UTX. Surprisingly, loss of H3K27me2
      results in global transcriptional derepression proportionally greatest in silent
      or weakly transcribed intergenic and genic regions and accompanied by an increase
      of H3K27ac and H3K4me1. H3K27me2 therefore sets a threshold that prevents random,
      unscheduled transcription all over the genome and even limits the activity of
      highly transcribed genes. PRC1-type complexes also have global roles.
      Unexpectedly, we find a pervasive distribution of histone H2A ubiquitylated at
      lysine 118 (H2AK118ub) outside of canonical PcG target regions, dependent on the
      RING/Sce subunit of PRC1-type complexes. We show, however, that H2AK118ub does
      not mediate the global PRC2 activity or the global repression and is
      predominantly produced by a new complex involving L(3)73Ah, a homolog of
      mammalian PCGF3. 

PMID- 25986501
TI  - Weapon carrying and psychopathic-like features in a population-based sample of
      Finnish adolescents.
AB  - We investigated the prevalence of juvenile weapon carrying and psychosocial and
      personality-related risk factors for carrying different types of weapons in a
      nationally representative, population-based sample of Finnish adolescents.
      Specifically, we aimed to investigate psychopathic-like personality features as a
      risk factor for weapon carrying. The participants were 15-16-year-old adolescents
      from the Finnish self-report delinquency study (n = 4855). Four different groups
      were formed based on self-reported weapon carrying: no weapon carrying, carrying
      knife, gun or other weapon. The associations between psychosocial factors,
      psychopathic-like features and weapon carrying were examined with multinomial
      logistic regression analysis. 9% of the participants had carried a weapon in the
      past 12 months. Adolescents with a history of delinquency, victimization and
      antisocial friends were more likely to carry weapons in general; however,
      delinquency and victimization were most strongly related to gun carrying, while
      perceived peer delinquency (antisocial friends) was most strongly related to
      carrying a knife. Better academic performance was associated with a reduced
      likelihood of carrying a gun and knife, while feeling secure correlated with a
      reduced likelihood of gun carrying only. Psychopathic-like features were related
      to a higher likelihood of weapon carrying, even after adjusting for other risk
      factors. The findings of the study suggest that adolescents carrying a weapon
      have a large cluster of problems in their lives, which may vary based on the type
      of weapon carried. Furthermore, psychopathic-like features strongly relate to a
      higher risk of carrying a weapon.

PMID- 25986500
TI  - A story of change: The influence of narrative on African-Americans with diabetes.
AB  - OBJECTIVE: To understand if narratives can be effective tools for diabetes
      empowerment, from the perspective of African-American participants in a program
      that improved diabetes self-efficacy and self-management. METHODS: In-depth
      interviews and focus groups were conducted with program graduates. Participants
      were asked to comment on the program's film, storytelling, and role-play, and
      whether those narratives had contributed to their diabetes behavior change. An
      iterative process of coding, analyzing, and summarizing transcripts was completed
      using the framework approach. RESULTS: African-American adults (n=36) with
      diabetes reported that narratives positively influenced the diabetes behavior
      change they had experienced by improving their attitudes/beliefs while increasing
      their knowledge/skills. The social proliferation of narrative - discussing
      stories, rehearsing their messages with role-play, and building social support
      through storytelling - was reported as especially influential. CONCLUSION:
      Utilizing narratives in group settings may facilitate health behavior change,
      particularly in minority communities with traditions of storytelling. Theoretical
      models explaining narrative's effect on behavior change should consider the
      social context of narratives. PRACTICE IMPLICATIONS: Narratives may be promising
      tools to promote diabetes empowerment. Interventions using narratives may be more
      effective if they include group time to discuss and rehearse the stories
      presented, and if they foster an environment conducive to social support among
      participants.

PMID- 25986503
TI  - Alzheimer disease: The involvement of TREM2 R47H variant in Alzheimer disease
      confirmed, but mechanisms remain elusive.

PMID- 25986502
TI  - Dementia: Risk prediction models in dementia prevention.

PMID- 25986504
TI  - Neuro-oncology: The many challenges of treating elderly glioblastoma patients.

PMID- 25986506
TI  - Spinal muscular atrophy--recent therapeutic advances for an old challenge.
AB  - In the past decade, improved understanding of spinal muscular atrophy (SMA)
      aetiopathogenesis has brought us to a historical turning point: we are at the
      verge of development of disease-modifying treatments for this hitherto incurable
      disease. The increasingly precise delineation of molecular targets within the
      survival of motor neuron (SMN) gene locus has led to the development of promising
      therapeutic strategies. These novel avenues in treatment for SMA include gene
      therapy, molecular therapy with antisense oligonucleotides, and small molecules
      that aim to increase expression of SMN protein. Stem cell studies of SMA have
      provided an in vitro model for SMA, and stem cell transplantation could be used
      as a complementary strategy with a potential to treat the symptomatic phases of
      the disease. Here, we provide an overview of established data and novel insights
      into SMA pathogenesis, including discussion of the crucial function of the SMN
      protein. Preclinical evidence and recent advances from ongoing clinical trials
      are thoroughly reviewed. The final remarks are dedicated to future clinical
      perspectives in this rapidly evolving field, with a broad discussion on the
      comparison between the outlined therapeutic approaches and the remaining open
      questions. 

PMID- 25986507
TI  - Castleman Disease.

PMID- 25986505
TI  - Toward stem cell-based phenotypic screens for neurodegenerative diseases.
AB  - In the absence of a single preventive or disease-modifying strategy,
      neurodegenerative diseases are becoming increasingly prevalent in our ageing
      population. The mechanisms underlying neurodegeneration are poorly understood,
      making the target-based drug screening strategies that are employed by the
      pharmaceutical industry fraught with difficulty. However, phenotypic screening in
      neurons and glia derived from patients is now conceivable through unprecedented
      developments in reprogramming, transdifferentiation, and genome editing. We
      outline progress in this nascent field, but also consider the formidable hurdles
      to identifying robust, disease-relevant and screenable cellular phenotypes in
      patient-derived cells. We illustrate how analysis in the simple baker's yeast
      cell Saccharaomyces cerevisiae is driving discovery in patient-derived neurons,
      and how approaches in this model organism can establish a paradigm to guide the
      development of stem cell-based phenotypic screens. 

PMID- 25986508
TI  - Should the Urologist Treat Castration Resistant Prostate Cancer? No.

PMID- 25986509
TI  - Bricker Conduit for Pediatric Urinary Diversion--Should we Still Offer It?
AB  - PURPOSE: We sought to evaluate long-term outcomes of the Bricker conduit urinary
      diversion in children. MATERIALS AND METHODS: We retrospectively reviewed the
      database of a single tertiary center for children who had undergone ileal conduit
      between 1981 and 2011. Patients followed for less than 1 year were excluded.
      Patient files were reviewed for demographics, diversion indication, preoperative
      imaging, surgical details, hospital readmissions and followup data. Renal
      function at baseline and last followup was assessed by estimated glomerular
      filtration rate, calculated using the modified Schwartz or MDRD (Modified Diet in
      Renal Disease) formula. Growth charts elucidated patient growth patterns, while
      an internally designed quality of life questionnaire demonstrated patient and
      family satisfaction with the procedure. RESULTS: We evaluated 29 children who
      underwent Bricker conduit at a median age of 10 years (range 2 to 18) and were
      followed for a median of 91 months (16 to 389). Neuropathic bladder was the
      underlying diagnosis in 72.4% of cases. Hydronephrosis improved or remained
      stable in 39 of 55 studied renal units (70.9%). Although no statistically
      significant difference was observed between mean +/- SD baseline (64.5 +/- 46
      ml/minute/1.73 m(2)) and last followup estimated glomerular filtration rate (54.1
      +/- 44.9 ml/minute/1.73 m(2)), chronic kidney disease stage had worsened in 13
      patients (44.8%), end-stage kidney disease had developed in 11 patients and 9
      patients had died. Six patients underwent undiversion after stabilization of
      renal function. Linear growth was negatively affected in 12 patients (41.4%), and
      85% reported poor quality of life. A total of 19 hospital readmissions were
      required in 14 patients to treat diversion related complications. CONCLUSIONS:
      The Bricker conduit does not seem to halt renal deterioration in children.
      Negative impact on growth and quality of life, and the anticipated rate of
      complications are significant limitations of the procedure in the pediatric
      population.

PMID- 25986510
TI  - Predicting Length of Stay Following Radical Nephrectomy Using the National
      Surgical Quality Improvement Program Database.
AB  - PURPOSE: Length of stay is frequently used to measure the quality of health care,
      although its predictors are not well studied in urology. We created a predictive
      model of length of stay after nephrectomy, focusing on preoperative variables.
      MATERIALS AND METHODS: We used the NSQIP database to evaluate patients older than
      18 years who underwent nephrectomy without concomitant procedures from 2007 to
      2011. Preoperative factors analyzed for univariate significance in relation to
      actual length of stay were then included in a multivariable linear regression
      model. Backward elimination of nonsignificant variables resulted in a final model
      that was validated in an institutional external patient cohort. RESULTS: Of the
      1,527 patients in the NSQIP database 864 were included in the training cohort
      after exclusions for concomitant procedures or lack of data. Median length of
      stay was 3 days in the training and validation sets. Univariate analysis revealed
      27 significant variables. Backward selection left a final model including the
      variables age, laparoscopic vs open approach, and preoperative hematocrit and
      albumin. For every additional year in age, point decrease in hematocrit and point
      decrease in albumin the length of stay lengthened by a factor of 0.7%, 2.5% and
      17.7%, respectively. If an open approach was performed, length of stay increased
      by 61%. The R(2) value was 0.256. The model was validated in a 427 patient
      external cohort, which yielded an R(2) value of 0.214. CONCLUSIONS: Age,
      preoperative hematocrit, preoperative albumin and approach have significant
      effects on length of stay for patients undergoing nephrectomy. Similar predictive
      models could prove useful in patient education as well as quality assessment.

PMID- 25986511
TI  - Molecular Determinants of Metastasis in Renal Cell Cancer: Tracking Down the Real
      Killer.

PMID- 25986512
TI  - Should Fluorescence Mapping be Used to Guide Pelvic Lymph Node Dissection?

PMID- 25986513
TI  - Should the Urologist Treat Castration Resistant Prostate Cancer? Yes.

PMID- 25986515
TI  - Can We Correct Hypospadias with a Staged Operation? If not, are We Bold Enough to
      Report it?

PMID- 25986516
TI  - Adenocarcinoma Arising from a Bladder Diverticulum.

PMID- 25986517
TI  - Optimal Antibiotic Use to Prevent Post-Prostate Biopsy Infection.

PMID- 25986518
TI  - Transdermal delivery of bovine milk vesicles in patients with multiple sclerosis:
      A novel strategy to induce MOG-specific tolerance.
AB  - Recently, butyrophilin (BTN) - a protein which shares cross-reactive epitopes
      with myelin oligodendrocyte glycoprotein (MOG) - has been found in milk. A high
      amount of milk BTN has been reported in the outer membrane of vesicular
      structures known as exosome and milk fat globule membrane (MFGM). These vesicles
      can act as Trojan horses, passing their BTN content through epidermis or other
      biologic barriers of the body. By altering the dose schedule and route of
      administration, the BTN-bearing vesicles (exosomes and MFGMs) may acquire enough
      potential to be used in MOG-specific immunotherapy program. Regarding above
      evidence and considering immunological characteristics of skin-associated
      lymphoid tissue (SALT), transdermal delivery of bovine milk vesicles, whether
      through topical administration of bovine milk or by using epicutaneous
      administration techniques, could be considered as an intriguing approach to
      induce MOG-specific tolerance in patients with multiple sclerosis. 

PMID- 25986519
TI  - Identifying research needs for wheelchair transfers in the built environment.
AB  - PURPOSE: The purpose of this study is to describe the results of focus groups
      held during the Independent Wheelchair Transfer (IWT) Workgroup. The aims were to
      facilitate exchange of ideas on (1) the impact of the built environment on the
      wheelchair transfer process within the community (i.e. moving from wheelchair to
      and from other surfaces (e.g. furniture, toilet seat, bath bench, car seat) to
      participate in daily activities), (2) wheelchair users' needs during transfers in
      the built environment, and (3) future research directions. METHOD: Live web-based
      conferencing using Adobe Connect technology (Clarix Technologies, Inc.,
      Pittsford, NY) was utilized to conduct three focus groups composed of experts in
      the field of assistive technology. Investigators independently reviewed focus
      group meeting transcripts and used qualitative methods to identify main themes.
      RESULT: Thirty-one experts in assistive technology and related fields
      participated in focus groups. Nine main themes were found including the effect of
      transfer skills training, space considerations in the built environment,
      wheelchair configuration, and the interaction between the built environment, user
      preferences, and transfer techniques. All groups raised issues about the transfer
      process in areas of the built environment with limited access, the effect of
      wheelchair users' transfer techniques, and user preferences during transfers.
      CONCLUSIONS: The area of independent transfers is multi-faceted and several
      factors require consideration when contemplating environmental changes to improve
      accessibility for wheelchair users. Obvious opportunity exists for research which
      could lead to advances in transfer technology, environments, and techniques for
      wheelchair users. Implications for Rehabilitation Tremendous opportunities for
      research collaborations in the field of assistive technology: To develop new
      terminology to describe wheelchair transfers. To improve the design of the built
      environment for wheelchair users. To investigate wheelchair transfer training
      techniques.

PMID- 25986520
TI  - Erratum to: The Impact of Chronic Opioid Use on Colonoscopy Outcomes.

PMID- 25986521
TI  - Anesthesiologist-Administered Gastrointestinal Sedation: Time to Put It to Sleep?

PMID- 25986522
TI  - Toward the Effective Co-management of Patients with Cirrhosis by Primary Care
      Providers and Specialists.

PMID- 25986523
TI  - Metallic Stents for Benign Extrahepatic Biliary Stricture: In Praise of Self
      Expansion?

PMID- 25986524
TI  - Hospitalized Patients with Cirrhosis Should Be Screened for Clostridium difficile
      Colitis.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is an important public health
      problem in hospitalized patients. Patients with cirrhosis are particularly at
      risk of increased associated morbidity, mortality, and healthcare utilization
      from CDI. AIM: The aim of this study was to assess the pharmacoeconomic impact of
      CDI screening on hospitalized patients with cirrhosis. METHODS: A Markov model
      was used to compare costs and outcomes of two strategies for the screening of
      CDI. The first strategy consisted of screening all patients for CDI and treating
      if detected (screening). In the second strategy, only patients found to have
      symptomatic CDI were treated (no screening). The probability of underlying CDI
      prevalence, symptomatic CDI infection, and likelihood of recurrent infection were
      varied in a sensitivity analysis. The costs of antibiotics and hospitalization
      were also assessed. Differences in outcome were expressed in ratio of the total
      costs associated with screening to the total costs associated without screening.
      RESULTS: The results of our model showed that screening for CDI was consistently
      associated with improved healthcare outcomes and decreased healthcare utilization
      across all variables in the one- and two-way sensitivity analyses. Using baseline
      assumptions, the costs associated with the no screening strategy were 3.54 times
      that of the screening strategy. Moreover, the mortality for symptomatic CDI was
      lower in the screening strategy than the no screening strategy. CONCLUSION: The
      screening strategy results in less healthcare utilization and improved clinical
      outcomes. Screening for CDI measures favorably.

PMID- 25986525
TI  - Interferon-Free Regimens for Chronic Hepatitis C: Barriers Due to Treatment
      Candidacy and Insurance Coverage.
AB  - BACKGROUND: Recently developed interferon- and ribavirin-free regimens to treat
      hepatitis C virus infection (HCV) have low side effect profile accompanied by
      high efficacy. AIM: To assess the potential access to these regimens using the
      most recent data on candidacy and insurance coverage for HCV-positive Americans.
      METHODS: The National Health and Nutrition Examination Survey (NHANES) cycles
      2005-2008 and 2009-2012 were used in this cross-sectional study. RESULTS: A total
      of 10,799 and 11,840 adult (18+) NHANES participants were included from the two
      cycles, respectively. Of these, 1.19 and 0.94%, respectively, showed detectable
      viremia (HCV+). The proportion of HCV+ individuals aged >=65 increased from 1.7
      to 6.8% (p = 0.0144). HCV+ individuals were less likely to be insured than HCV-
      regardless of the study year (HCV+: 63.8% vs. HCV-: 80.1%, p = 0.0005). Between
      the study cycles, the rates of insurance coverage (60.2 and 67.4%, respectively)
      and treatment eligibility based on medical contraindications for interferon-based
      treatment (66.6 and 74.1%, respectively) were not different (p > 0.05). With
      minimal contraindications for interferon- and ribavirin-free treatment, 95.1 and
      97.7% of HCV+ patients could be eligible for treatment despite aging of the study
      population and unchanged rates of comorbid conditions. Considering both treatment
      eligibility and insurance coverage, potential access to anti-HCV treatment
      increased from 35.1% for interferon-based to 66.6% for interferon-free regimens
      (p = 0.0003). CONCLUSIONS: A large proportion of HCV+ individuals remain
      uninsured or under-insured. The lack of adequate coverage limits their access to
      the newly developed interferon- and ribavirin-free regimens for HCV that are
      highly effective with minimal contraindications.

PMID- 25986526
TI  - Does Vitamin D Protect the Gut Mucosal Barrier? Mechanistic Insights from
      Experimental Colitis.

PMID- 25986527
TI  - Associations Between Parameters of Glucose and Lipid Metabolism and Risk of
      Colorectal Neoplasm.
AB  - BACKGROUND: Diabetes and dyslipidemia have been linked to an increased risk of
      colorectal neoplasm (CRN). However, previous studies evaluating these
      associations have shown inconsistent results, and large-scale studies are few in
      number. AIM: To investigate the associations between the parameters of glucose
      and lipid metabolism and the presence of CRN. METHODS: A cross-sectional study
      was performed on 38,490 Korean adults aged >=30 years undergoing their first
      colonoscopy as part of routine preventive health care between 2010 and 2011.
      RESULTS: The prevalence of overall CRN increased with increasing levels of
      glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin
      resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein
      cholesterol (LDL-C), and apolipoprotein B (ApoB) and with decreasing level of
      apolipoprotein A1 (ApoA1). The adjusted prevalence ratios for overall CRN
      comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin,
      HOMA-IR, triglycerides, total cholesterol, LDL-C, ApoB, and ApoA-1 were 1.83 (95%
      CI 1.62-2.06), 1.17 (95% CI 1.03-1.33), 1.09 (95% CI 0.97-1.23), 1.22 (95% CI
      1.08-1.37), 1.31 (95% CI 1.16-1.48), 1.19 (95 % CI 1.07-1.33), 1.38 (95% CI 1.23
      1.54), 1.30 (95% CI 1.14-1.47), and 0.85 (95% CI 0.76-0.95), respectively. There
      was also a significant association between higher levels of glucose, LDL-C, and
      ApoB with a higher prevalence of advanced CRN. Moreover, the risk of CRN
      increased further in cases in which the parameters of glucose metabolism and
      lipid metabolism worsened simultaneously. CONCLUSIONS: The levels of parameters
      of glucose and lipid metabolism are significantly associated with the prevalence
      of CRN. Altered glucose and lipid metabolism may contribute to the development of
      CRN.

PMID- 25986528
TI  - The Risks of Incident and Recurrent Clostridium difficile-Associated Diarrhea in
      Chronic Kidney Disease and End-Stage Kidney Disease Patients: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: The objective of this systematic review and meta-analysis was to
      assess the risks of incident and recurrent Clostridium difficile-associated
      diarrhea in patients with chronic kidney disease (CKD) and end-stage renal
      disease (ESRD) requiring dialysis. METHODS: A literature search was performed
      from inception to February 2015. Studies that reported relative risks, odds
      ratios, or hazard ratios comparing the risks of C. difficile-associated diarrhea
      in patients with CKD or ESRD versus those without CKD or ESRD were included.
      Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using
      a random-effect, generic inverse variance method. RESULTS: Twenty studies (nine
      case-control, seven cohort, and four cross-sectional studies with 162,218,041
      patients) were included in the meta-analysis. Pooled RRs of C. difficile
      associated diarrhea in patients with CKD and ESRD were 1.95 (95% CI 1.81-2.10)
      and 2.63 (95% CI 2.04-3.38), respectively. When meta-analysis was limited only to
      cohort and case-control studies with confounder-adjusted analysis, the pooled RRs
      of C. difficile-associated diarrhea in patients with CKD and ESRD were 1.89 (95%
      CI 1.75-2.05) and 2.50 (95% CI 1.49-4.17), respectively. The pooled RR of
      recurrent C. difficile-associated diarrhea in patients with CKD was 2.61 (95% CI
      1.53-4.44). Data on the risk of recurrent C. difficile-associated diarrhea were
      limited. CONCLUSION: This meta-analysis demonstrates significantly increased
      risks of incident and recurrent C. difficile-associated diarrhea in patients with
      CKD. Furthermore, the magnitude of increased risk of C. difficile-associated
      diarrhea in ESRD patients is even higher.

PMID- 25986529
TI  - Patatin-Like Phospholipase Domain-Containing 3 I148M Variant Is Associated with
      Liver Steatosis and Fat Distribution in Chronic Hepatitis B.
AB  - BACKGROUND: The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has
      been associated with liver steatosis and disease progression in nonalcoholic
      steatohepatitis and chronic hepatitis C. AIMS: The aim of the present study was
      to evaluate the influence of the PNPLA3 I148M polymorphisms on the clinical,
      histological, viral, and host parameters in Italian patients with chronic
      hepatitis B (CHB). METHODS: Ninety-nine patients with CHB entered the study and
      underwent a clinical, histological, virological, and biochemical evaluation.
      PNPLA3 (p.I148M) variants were genotyped. RESULTS: PNPLA3 rare variant (148M) was
      significantly associated with liver steatosis (p = 0.0019) and cholesterol (p =
      0.04) levels, but not with fibrosis or histological activity index. The 13
      patients with severe liver steatosis (score > 3) (38%) were more frequently
      homozygous for PNPLA3 148M variant than the 86 without (6%, p = 0.003). At
      logistic regression analysis, severe steatosis was independently associated with
      the rare allele (p = 0.001) and waist circumference, but not with body mass index
      (BMI). CONCLUSIONS: In our CHB patients, the PNPLA3 polymorphisms influenced the
      development of liver steatosis, but not fibrosis status. The association of
      PNPLA3 p.I148M with liver steatosis increased with the greater amount of
      abdominal fat, irrespective of BMI.

PMID- 25986530
TI  - Ubiquinone-10 alters mechanical properties and increases stability of
      phospholipid membranes.
AB  - Ubiquinone-10 is mostly known for its role as an electron and proton carrier in
      aerobic cellular respiration and its function as a powerful antioxidant.
      Accumulating evidence suggest, however, that this well studied membrane component
      could have several other important functions in living cells. The current study
      reports on a previously undocumented ability of ubiquinone-10 to modulate the
      mechanical strength and permeability of lipid membranes. Investigations of DPH
      fluorescence anisotropy, spontaneous and surfactant induced leakage of
      carboxyfluorescein, and interactions with hydrophobic and hydrophilic surfaces
      were used to probe the effects caused by inclusion of ubiquinone-10 in the
      membrane of phospholipid liposomes. The results show that ubiquinone in
      concentrations as low as 2 mol% increases the lipid packing order and condenses
      the membrane. The altered physicochemical properties result in a slower rate of
      release of hydrophilic components, and render the membrane more resistant towards
      rupture. As judged from comparative experiments using the polyisoprenoid alcohol
      solanesol, the quinone moiety is essential for the membrane stabilizing effects
      to occur. Our findings imply that the influence of ubiquinone-10 on the
      permeability and mechanical properties of phospholipid membranes is similar to
      that of cholesterol. The reported data indicate, however, that the molecular
      mechanisms are different in the two cases.

PMID- 25986532
TI  - [Measuring subjective social status in health research with a German version of
      the MacArthur Scale].
AB  - In health research, socio-economic status (SES) is traditionally assessed using
      objective indicators (education, occupation, income). For a couple of years,
      there has been a growing body of studies that additionally assess the subjective
      social status (SSS) of respondents, mostly using the MacArthur Scale. The aim of
      this study was to examine the construct validity of a German-language version of
      this instrument and to investigate whether SSS is associated with health over and
      above objective SES. Analyses were based on data from a population-based pilot
      study carried out within the 'German Health Update' (GEDA) study conducted by the
      Robert Koch Institute (n = 1,571; age: 18-79 years). SSS was measured with the
      MacArthur scale asking respondents to place themselves on a 10-rung "social
      ladder". The strongest correlations to SSS were found with measures of similar
      constructs such as a multidimensional index of objective SES, income level,
      occupational position and educational attainment (r = 0.32-0.60; p < 0.001).
      Weaker correlations were found between SSS and measures of dissimilar constructs
      such as social support, mental well-being, depressiveness, and body-mass-index (r
      = - 0.29-0.30; p < 0.001). Factor analysis did not show considerable loadings of
      SSS on factors of mental well-being and depressiveness. After adjusting for age,
      education, occupation, and income, lower SSS remained significantly associated
      with higher odds of adverse health (p < 0.05). The findings of this study provide
      support for the convergent and discriminant validity of the MacArthur Scale and
      indicate that self-perceptions of social disadvantage may have health
      implications beyond the impact of objective SES. 

PMID- 25986533
TI  - [Not Available].

PMID- 25986531
TI  - Cross-Cultural Approach of Postpartum Depression: Manifestation, Practices
      Applied, Risk Factors and Therapeutic Interventions.
AB  - It is a well known fact that postpartum depression (PPD) is a global phenomenon
      that women may experience, regardless of cultural identity and beliefs. This
      literature review presents the cultural beliefs and postnatal practices around
      the world, in each continent and people's origins, looking through the extent to
      which they contribute positively or negatively to the onset of the disease. 106
      articles were used in this research, through a systematic electronic search of
      Pubmed (Medline) and Scopus. Comparison is also made between the prevalence, the
      risk factors and the different ways of appearance of the disease around the world
      and among immigrants. Finally, the initiatives and interventions made so far by
      the governments and institutions with a view to prevent and address this global
      problem are presented. The results showed (a) that different cultures share the
      same risk factors towards the disease (b) significant differences in the
      prevalence of the disease among both Western and non Western cultures and between
      the cultures themselves (c) more tendencies for somatization of depressive
      symptoms in non-Western cultures, (d) different postnatal practices between
      cultures, which are not always effective (e) the more non-West a culture is, the
      less interventions concern on mental health; the same phenomenon is observed on
      populations burdened by immigration. The beliefs held by culture should be taken
      seriously in detecting of PPD, as well as the assessment of the needs of women
      who have recently given birth. 

PMID- 25986535
TI  - An observational study of glycemic control in canagliflozin treated patients.
AB  - OBJECTIVE: To evaluate changes in glycemic control following the initial
      canagliflozin pharmacy claim in a real-world population. RESEARCH DESIGN AND
      METHODS: A retrospective cohort analysis of adult patients with type 2 diabetes
      mellitus (T2DM) was conducted using 2013 medical, pharmacy and laboratory claims
      from the Inovalon MORE 2 Registry. Patients with T2DM aged >=18 years with >=60
      days of canagliflozin supply and HbA1c test results within 120 days before and
      >=60 days after initial canagliflozin claim (defined as index date) were
      included. The differences between HbA1c levels pre- and post-index were assessed.
      Changes pre- and post-index in Healthcare Effectiveness Data and Information Set
      (HEDIS) glycemic control criteria of HbA1c <7% and <8% and poor control of HbA1c
      >9% were evaluated. Subgroup analyses of patients with HbA1c >7% at baseline and
      patients aged >=65 were also conducted. RESULTS: Among the 268 patients meeting
      the study criteria, mean HbA1c pre-index was 8.3% and post-index was 7.6%; the
      mean reduction in HbA1c pre-post index was 0.7% (95% CI: 0.6%, 0.9%). The
      proportions of patients meeting the HEDIS glycemic control measures (HbA1c <7%,
      <8% and poor control of >9%) improved and was significantly different pre- and
      post-index (all p < 0.001). Of the patients with an HbA1c >7% prior to index (81%
      of the cohort; mean pre-index HbA1c = 8.8%), HbA1c was reduced by 0.9% (95% CI:
      0.8%, 1.1%). The aged >=65 subgroup consisted of 15% of the cohort, with a pre
      index HbA1c of 8.3%. The mean reduction in HbA1c test results pre- and post
      canagliflozin index was 0.6% (95% CI: 0.4%, 0.9%). This analysis did not adjust
      for changes in antihyperglycemic agents during the study period. CONCLUSION:
      Patients with T2DM were observed to have improved glycemic control following
      initial canagliflozin pharmacy claim as measured by HbA1c change and attainment
      of specific glycemic control criteria.

PMID- 25986534
TI  - Cardiac gene expression data and in silico analysis provide novel insights into
      human and mouse taste receptor gene regulation.
AB  - G protein-coupled receptors are the principal mediators of the sweet, umami,
      bitter, and fat taste qualities in mammals. Intriguingly, the taste receptors are
      also expressed outside of the oral cavity, including in the gut, airways, brain,
      and heart, where they have additional functions and contribute to disease.
      However, there is little known about the mechanisms governing the transcriptional
      regulation of taste receptor genes. Following our recent delineation of taste
      receptors in the heart, we investigated the genomic loci encoding for taste
      receptors to gain insight into the regulatory mechanisms that drive their
      expression in the heart. Gene expression analyses of healthy and diseased human
      and mouse hearts showed coordinated expression for a subset of chromosomally
      clustered taste receptors. This chromosomal clustering mirrored the cardiac
      expression profile, suggesting that a common gene regulatory block may control
      the taste receptor locus. We identified unique domains with strong regulatory
      potential in the vicinity of taste receptor genes. We also performed de novo
      motif enrichment in the proximal promoter regions and found several
      overrepresented DNA motifs in cardiac taste receptor gene promoters corresponding
      to ubiquitous and cardiac-specific transcription factor binding sites. Thus,
      combining cardiac gene expression data with bioinformatic analyses, this study
      has provided insights into the noncoding regulatory landscape for taste GPCRs.
      These findings also have broader relevance for the study of taste GPCRs outside
      of the classical gustatory system, where understanding the mechanisms controlling
      the expression of these receptors may have implications for future therapeutic
      development. 

PMID- 25986536
TI  - A memory advantage for property.
AB  - People's access to resources depends on their status as the owner of particular
      items. To respect property, people need to remember who owns which objects. We
      test the hypothesis that people possess enhanced memory for ownership relations
      compared to unrelated objects. Participants viewed a sequence of 10 person-object
      pairs before completing a surprise associative memory test in which they matched
      each person with the previously paired object. We varied the description of the
      person-object pairs in the instructions. Across three experiments, participants
      showed better recall when the person was described as the owner of the object
      compared to being unrelated. Furthermore, memory for property was better than a
      physical relation (bumping), whereas it did not differ from mental relations
      (wanting and thinking). These patterns were observed both for memory of items
      (Experiments 1 and 2) and perceptual details (Experiment 3). We discuss
      implications for how people remember other people's property. 

PMID- 25986537
TI  - Conservative treatment of de novo renal carcinoma on kidney graft.
AB  - BACKGROUND: De novo renal carcinoma in kidney transplants is an uncommon but not
      exceptional condition and is of significant importance due to the potential for
      recipient mortality and graft loss. The aim of our study was to determine the
      management and outcome of these tumors in our Kidney Transplantation Unit.
      MATERIAL AND METHODS: We analyzed cases of de novo kidney tumors among patients
      who underwent transplantation in the last 17 years in our Kidney Transplantation
      Unit. We detected 3 cases of clear cell carcinoma and 1 case of papillary
      carcinoma on the graft. We conducted follow-up on the tumor and renal function
      and analyzed patient responses to changes in immunosuppression. RESULTS:
      Tumorectomy was performed in all cases, and subsequent transplantectomy was
      required for patients with papillary carcinoma. None of the patients had relevant
      surgical complications. We also changed the patients' regimen to a proliferation
      signal inhibitor or mTOR inhibitor and completely withdrew all anticalcineurin
      agents. With a mean follow-up of 43.5 months (15-61), the 3 patients with clear
      cell carcinoma survived with good graft function and with no evidence of tumor
      recurrence. The patient with papillary carcinoma underwent follow-up at another
      hospital center. CONCLUSIONS: Conservative surgery along with conversion to a
      proliferation signal inhibitor appears to be a safe option for treating primary
      tumors in kidney grafts and offers good oncological and renal function results in
      the short and medium term.

PMID- 25986538
TI  - Human mass balance, metabolite profile and identification of metabolic enzymes of
      [14C]ASP015K, a novel oral janus kinase inhibitor.
AB  - 1. The human mass balance of (14)C-labelled ASP015K ([(14)C]ASP015K), an orally
      bioavailable Janus kinase (JAK) inhibitor, was characterized in six healthy male
      subjects after a single oral dose of [(14)C]ASP015K (100 mg, 3.7 MBq) in
      solution. [(14)C]ASP015K was rapidly absorbed with tmax of 1.6 and 1.8 h for
      ASP015K and total radioactivity in plasma, respectively. Mean recovery in urine
      and feces amounted to 36.8% and 56.6% of the administered dose, respectively. The
      main components of radioactivity in plasma and urine were ASP015K and M2 (5'-O
      sulfo ASP015K). In feces, ASP015K and M4 (7-N-methyl ASP015K) were the main
      components. 2. In vitro study of ASP015K metabolism showed that the major isozyme
      contributing to the formation of M2 was human sulfotransferase (SULT) 2A1 and of
      M4 was nicotinamide N-methyltransferase (NNMT). 3. The in vitro intrinsic
      clearance (CLint_in vitro) of M4 formation from ASP015K in human liver cytosol
      (HLC) was 11-fold higher than that of M2. The competitive inhibitory effect of
      nicotinamide on M4 formation in the human liver was considered the reason for
      high CLint_in vitro of M4 formation, while each metabolic pathway made a near
      equal contribution to the in vivo elimination of ASP015K. ASP015K was cleared by
      multiple mechanisms.

PMID- 25986539
TI  - Disposition, metabolism and mass balance of delafloxacin in healthy human
      volunteers following intravenous administration.
AB  - 1. The pharmacokinetics and disposition of delafloxacin was investigated
      following a single intravenous (300 mg, 100 uCi) dose to healthy male subjects.
      2. Mean Cmax, AUC0-infinity, Tmax and t1/2 values for delafloxacin were 8.98
      ug/mL, 21.31 ug h/mL, 1 h and 2.35 h, respectively, after intravenous dosing. 3.
      Radioactivity was predominantly excreted via the kidney with 66% of the
      radioactive dose recovered in the urine. Approximately 29% of the radioactivity
      was recovered in the faeces, giving an overall mean recovery of 94% administered
      radioactivity. 4. The predominant circulating components were identified as
      delafloxacin and a direct glucuronide conjugate of delafloxacin. 

PMID- 25986540
TI  - Effectiveness of the Liverpool care pathway for the dying in residential care
      homes: An exploratory, controlled before-and-after study.
AB  - BACKGROUND: Clinical pathways aim to ensure that individuals receive appropriate
      evidence-based care and interventions, with the Liverpool Care Pathway for the
      Dying Patient focusing on end of life. However, controlled studies of the
      Liverpool Care Pathway for the Dying Patient, particularly outside of cancer
      settings, are lacking. AIM: To compare the effects of the Liverpool Care Pathway
      for the Dying Patient and usual care on patients' symptom distress and well-being
      during the last days of life, in residential care homes. DESIGN: Exploratory,
      controlled before-and-after study. During a 15-month baseline, usual care was
      carried out in two areas. During the following 15-months, usual care continued in
      the control area, while residential care home staff implemented Liverpool Care
      Pathway for the Dying Patient use in the intervention area. The intervention was
      evaluated by family members completing retrospective symptom assessments after
      the patient's death, using the Edmonton Symptom Assessment System and Views of
      Informal Carers - Evaluation of Services. SETTINGS/PARTICIPANTS: Patients who
      died at all 19 residential care homes in one municipality in Sweden. RESULTS:
      Shortness of breath (estimate = -2.46; 95% confidence interval = -4.43 to -0.49)
      and nausea (estimate = -1.83; 95% confidence interval = -3.12 to -0.54) were
      significantly reduced in Edmonton Symptom Assessment System in patients in the
      intervention compared to the control area. A statistically significant
      improvement in shortness of breath was also found on the Views of Informal Carers
      - Evaluation of Services item (estimate = -0.47; 95% confidence interval = -0.85
      to -0.08). CONCLUSION: When implemented with adequate staff training and support,
      the Liverpool Care Pathway for the Dying Patient may be a useful tool for
      providing end-of-life care of elderly people at the end of life in non-cancer
      settings.

PMID- 25986542
TI  - Comparative analysis of the in vitro and in planta secretomes from Mycosphaerella
      fijiensis isolates.
AB  - Black Sigatoka, a devastating disease of bananas and plantains worldwide, is
      caused by the fungus Mycosphaerella fijiensis. Several banana cultivars such as
      'Yangambi Km 5' and Calcutta IV, have been known to be resistant to the fungus,
      but the resistance has been broken in 'Yangambi Km 5' in Costa Rica. Since the
      resistance of this variety still persists in Mexico, the aim of this study was to
      compare the in vitro and in planta secretomes from two avirulent and virulent M.
      fijiensis isolates using proteomics and bioinformatics approaches. We aimed to
      identify differentially expressed proteins in fungal isolates that differ in
      pathogenicity and that might be responsible for breaking the resistance in
      'Yangambi Km 5'. We were able to identify 90 protein spots in the secretomes of
      fungal isolates encoding 42 unique proteins and 35 differential spots between
      them. Proteins involved in carbohydrate transport and metabolism were more
      prevalent. Several proteases, pathogenicity-related, ROS detoxification and
      unknown proteins were also highly or specifically expressed by the virulent
      isolate in vitro or during in planta infection. An unknown protein representing a
      virulence factor candidate was also identified. These results demonstrated that
      the secretome reflects major differences between both M. fijiensis isolates. 

PMID- 25986543
TI  - Short-range splash discharge of peridioles in Nidularia.
AB  - The distinctive shapes of basidiomata in the bird's nest fungi reflect
      differences in the mechanism of splash discharge. In the present study, peridiole
      discharge was examined in Nidularia pulvinata using high-speed video. Nidularia
      pulvinata produces globose basidiomata that split open at maturity to expose 100
      or more peridioles within a gelatinous matrix. Each peridiole contains an
      estimated 7 million spores. The impact of water drops splashed the peridioles
      horizontally from the fruit body, along with globs of mucilage, at a mean
      velocity of 1.2 m s(-1). Discharged peridioles travelled for a maximum horizontal
      distance of 1.5 cm. This launch process contrasts with the faster vertical
      splashes of peridioles over distances of up to one metre from the flute-shaped
      fruit bodies of bird's nest fungi in the genera Crucibulum and Cyathus.
      Peridioles in these genera are equipped with a funicular cord that attaches them
      to vegetation, placing them in an ideal location for ingestion by browsing
      herbivores. The absence of cords in N. pulvinata and its use of a sloppy
      discharge mechanism suggest that it is more likely to be dispersed by animals
      feeding on the forest floor.

PMID- 25986541
TI  - Prediction of T stage in gastric carcinoma by enhanced CT and oral contrast
      enhanced ultrasonography.
AB  - BACKGROUND: The aim of this study is to explore the values of enhanced CT and
      oral contrast-enhanced ultrasonography on preoperative T stage in gastric
      carcinoma. METHODS: Forty patients with gastric carcinoma, including 27 males and
      13 females, were confirmed by endoscopy, operation, and pathology. The median age
      of these patients was 49 years old (25 to 73 years). There were 19 cases of well
      differentiated adenocarcinoma, 13 cases of poorly differentiated adenocarcinoma,
      5 cases of signet ring cell carcinoma, and 4 cases of mucinous adenocarcinoma by
      pathology. All these patients were examined by both enhanced CT and ultrasound
      examination simultaneously 1 week before surgery. T staging in all these gastric
      carcinomas was carried out by enhanced CT or oral contrast-enhanced
      ultrasonography, respectively, or by both of them. The statistical difference
      between T stage by imaging and pathological T stage was analyzed. RESULTS: In
      this study, there were 5 cases with T1 stage, 9 cases with T2 stage, 20 cases
      with T3 stage, and 6 cases with T4 stage by pathology; 5 cases with T1 stage, 7
      cases with T2 stage, 22 cases with T3 stage, and 6 cases with T4 stage by
      enhanced CT imaging with an accuracy of 75.00%; 6 cases with T1 stage, 7 cases
      with T2 stage, 22 cases with T3 stage, and 5 cases with T4 stage by
      ultrasonography examination, with an accuracy of 77.50%; and 4 cases with T1
      stage, 10 cases with T2 stage, 19 cases with T3 stage, and 7 cases with T4 stage
      by both enhanced CT imaging and ultrasonography examination, with an accuracy of
      85.00%. The accuracy of T staging in gastric carcinoma by both enhanced CT and
      ultrasound was higher than that either by enhanced CT or by ultrasound,
      respectively (P < 0.05). The anastomosis degree of the gastric carcinoma between
      enhanced CT and ultrasonography was kappa = 0.404. CONCLUSIONS: Combination
      diagnosis of enhanced CT and oral contrast-enhanced ultrasonography is helpful to
      improve the accuracy of T staging of gastric carcinoma before operations.

PMID- 25986544
TI  - A paralog of the proteinaceous elicitor SM1 is involved in colonization of maize
      roots by Trichoderma virens.
AB  - The biocontrol agent, Trichoderma virens, has the ability to protect plants from
      pathogens by eliciting plant defense responses, involvement in mycoparasitism, or
      secreting antagonistic secondary metabolites. SM1, an elicitor of induced
      systemic resistance (ISR), was found to have three paralogs within the T. virens
      genome. The paralog sm2 is highly expressed in the presence of plant roots. Gene
      deletion mutants of sm2 were generated and the mutants were found to overproduce
      SM1. The ability to elicit ISR in maize against Colletotrichum graminicola was
      not compromised for the mutants compared to that of wild type isolate. However,
      the deletion strains had a significantly lowered ability to colonize maize roots.
      This appears to be the first report on the involvement of an effector-like
      protein in colonization of roots by Trichoderma. 

PMID- 25986545
TI  - Identification of fungal ene-reductase activity by means of a functional
      screening.
AB  - Bioeconomy stresses the need of green processes promoting the development of new
      methods for biocatalyzed alkene reductions. A functional screening of 28 fungi
      belonging to Ascomycota, Basidiomycota, and Zygomycota isolated from different
      habitats was performed to analyze their capability to reduce C=C double bonds
      towards three substrates (cyclohexenone, alpha-methylnitrostyrene, and alpha
      methylcinnamaldehyde) with different electron-withdrawing groups, i.e., ketone,
      nitro, and aldehyde, respectively. Almost all the fungi showed this reducing
      activity. Noteworthy Gliomastix masseei, Mucor circinelloides, and Mucor plumbeus
      resulted versatile and effective, being able to reduce all the model substrates
      quickly and with high yields.

PMID- 25986547
TI  - Regulation of the aflatoxin-like toxin dothistromin by AflJ.
AB  - Biosynthesis by Aspergillus parasiticus of aflatoxin, one of the most potent
      known naturally occurring carcinogens, requires the activity of two regulatory
      proteins, AflR and AflJ, which are encoded by divergently transcribed genes
      within the aflatoxin gene cluster. Although the Zn2Cys6 transcription factor,
      AflR, has been well-studied, the role of AflJ as a transcription regulatory
      factor is not well understood. An AflJ-like gene (DsAflJ) is also present in the
      genome of the pine needle pathogen Dothistroma septosporum and is similarly
      divergently transcribed from an AflR orthologue (DsAflR). These genes are
      involved in biosynthesis of dothistromin, a toxic virulence factor related to
      aflatoxin. DsAflJ mutants produced low levels of dothistromin (<25-fold less than
      wild-type); this was in contrast to earlier work with A. parasiticus AflJ mutants
      in which aflatoxin production was more severely impaired. As expected,
      complementation of D. septosporum mutants with an intact copy of the DsAflJ gene
      regained production of wild-type levels of dothistromin, although levels were not
      further increased by over-expression in multi-copy strains. However, heterologous
      AflJ genes from Aspergillus spp. were unable to complement DsAflJ mutants,
      suggesting that the proteins function differently in these species. 

PMID- 25986546
TI  - Repetitive genomic sequences as a substrate for homologous integration in the
      Rhizopus oryzae genome.
AB  - The vast number of repetitive genomic elements was identified in the genome of
      Rhizopus oryzae. Such genomic repeats can be used as homologous regions for
      integration of plasmids. Here, we evaluated the use of two different repeats: the
      short (575 bp) rptZ, widely distributed (about 34 copies per genome) and the long
      (2053 bp) rptH, less prevalent (about 15 copies). The plasmid carrying rptZ
      integrated, but did so through a 2256-bp region of homology to the pyrG locus, a
      unique genomic sequence. Thus, the length of rptZ was below the minimal
      requirements for homologous strand exchange in this fungus. In contrast, rptH was
      used efficiently for homologous integration. The plasmid bearing this repeat
      integrated in multicopy fashion, with up to 25 copies arranged in tandem. The
      latter vector, pPyrG-H, could be a valuable tool for integration at homologous
      sequences, for such purposes as high-level expression of proteins.

PMID- 25986548
TI  - Fusarium sambucinum astA gene expressed during potato infection is a functional
      orthologue of Aspergillus nidulans astA.
AB  - Sulfate assimilation plays a vital role in prototrophic organisms. Orthologues of
      the alternative sulfate transporter (AstA) gene from Aspergillus nidulans were
      identified in the fungal plant pathogens Fusarium sambucinum and Fusarium
      graminearum. By physiological and biochemical analyses, the AstA orthologues were
      determined to be able to uptake sulfate from the environment. Similarly to astA
      in A. nidulans, the FsastA gene was found to be regulated by sulfur metabolite
      repression (SMR) in a sulfur-dependent manner. In contrast, the FgastA transcript
      was undetectable, however, when the FgastA gene was expressed heterologously in
      A. nidulans, the translated FgAstA protein acted as a sulfate transporter.
      Interestingly, F. sambucinum astA expression was remarkably augmented in infected
      potato tubers, despite the presence abundant sulfate and was found not to be
      correlated with plant resistance. 

PMID- 25986550
TI  - Bioluminescence patterns among North American Armillaria species.
AB  - Bioluminescence is widely recognized among white-spored species of Basidiomycota.
      Most reports of fungal bioluminescence are based upon visual light perception.
      When instruments such as photomultipliers have been used to measure fungal
      luminescence, more taxa have been discovered to produce light, albeit at a range
      of magnitudes. The present studies were undertaken to determine the prevalence of
      bioluminescence among North American Armillaria species. Consistent, constitutive
      bioluminescence was detected for the first time for mycelia of Armillaria
      calvescens, Armillaria cepistipes, Armillaria gemina, Armillaria nabsnona, and
      Armillaria sinapina and confirmed for mycelia of Armillaria gallica, Armillaria
      mellea, Armillaria ostoyae, and Armillaria tabescens. Emission spectra of mycelia
      representing all species had maximum intensity in the range 515-525 nm confirming
      that emitted light was the result of bioluminescence rather than
      chemiluminescence. Time series analysis of 1000 consecutive luminescence
      measurements revealed a highly significant departure from random variation.
      Mycelial luminescence of eight species exhibited significant, stable shifts in
      magnitude in response to a series of mechanical disturbance treatments, providing
      one mechanism for generating observed luminescence variation.

PMID- 25986549
TI  - Arbuscular mycorrhizal fungal diversity in the Tuber melanosporum brule.
AB  - The development of the fruiting body (truffle) of the ectomycorrhizal fungus
      Tuber melanosporum is associated with the production of an area (commonly
      referred to with the French word brule) around its symbiotic plant that has
      scanty vegetation. As truffles produce metabolites that can mediate fungal-plant
      interactions, the authors wondered whether the brule could affect the arbuscular
      mycorrhizal fungi (AMF) that colonize the patchy herbaceous plants inside the
      brule. A morphological evaluation of the roots of plants collected in 2009 from a
      T. melanosporum/Quercus pubescens brule in France has shown that the herbaceous
      plants are colonized by AMF to a great extent. An analysis of the 18S rRNA
      sequences obtained from roots and soil inside the brule has shown that the AMF
      community structure seemed to be affected in the soil inside the brule, where
      less richness was observed compared to outside the brule. 

PMID- 25986551
TI  - Phylogeny of type I polyketide synthases (PKSs) in fungal entomopathogens and
      expression analysis of PKS genes in Beauveria bassiana BCC 2660.
AB  - Entomopathogenic fungi are able to invade and kill insects. Various secondary
      metabolites can mediate the interaction of a fungal pathogen with an insect host
      and also help the fungus compete with other microbes. Here we screened 23
      isolates of entomopathogenic fungi for polyketide synthase (PKS) genes and
      amplified 72 PKS gene fragments using degenerate PCR. We performed a phylogenetic
      analysis of conserved ketosynthase and acyltransferase regions in these 72
      sequences and 72 PKSs identified from four insect fungal genome sequences. The
      resulting genealogy indicated 47 orthologous groups with 99-100 % bootstrap
      support, suggesting shared biosynthesis of identical or closely related compounds
      from different fungi. Three insect-specific groups were identified among the PKSs
      in reducing clades IIa, IIb, and III, which comprised PKSs from 12, 9, and 30
      fungal isolates, respectively. A IIa-IIb pair could be found in seven fungi.
      Expression analyses revealed that eleven out of twelve PKS genes identified in
      Beauveria bassiana BCC 2660 were expressed in culture. PKS genes from insect
      specific clades IIa and IIb were expressed only in insect-containing medium,
      while others were expressed only in PDB or in CYB, PDB and SDY. The data suggest
      the potential production of several polyketides in culture. 

PMID- 25986552
TI  - Respectful maternal and newborn care: building a common agenda.
AB  - In September, the World Health Organization released a statement on preventing
      and eliminating disrespect and abuse during facility-based childbirth. In
      addition to this important agenda, attention is also needed for the dignified
      care of newborns, who also deserve basic human rights and dignified care. In this
      commentary, we provide examples from the literature and other sources of where
      respectful care for newborns has been lacking and we give examples of
      opportunities for integration of maternal and newborn health care going forward.
      We illustrate the need for respectful treatment and consideration across the
      continuum of care: for mothers, stillbirths, and all newborns, including those
      born too soon and those who die in infancy. We explain the need to document cases
      of neglect and abuse, count all births and deaths, and to include newborns and
      stillbirths in the respectful care agenda and the post-2015 global reproductive
      care frameworks. 

PMID- 25986553
TI  - Culturally appropriate methodology in obtaining a representative sample of South
      Australian Aboriginal adults for a cross-sectional population health study:
      challenges and resolutions.
AB  - BACKGROUND: The considerably lower average life expectancy of Aboriginal and
      Torres Strait Islander Australians, compared with non-Aboriginal and non-Torres
      Strait Islander Australians, has been widely reported. Prevalence data for
      chronic disease and health risk factors are needed to provide evidence based
      estimates for Australian Aboriginal and Torres Strait Islanders population health
      planning. Representative surveys for these populations are difficult due to
      complex methodology. The focus of this paper is to describe in detail the
      methodological challenges and resolutions of a representative South Australian
      Aboriginal population-based health survey. METHODS: Using a stratified multi
      stage sampling methodology based on the Australian Bureau of Statistics 2006
      Census with culturally appropriate and epidemiological rigorous methods, 11,428
      randomly selected dwellings were approached from a total of 209 census collection
      districts. All persons eligible for the survey identified as Aboriginal and/or
      Torres Strait Islander and were selected from dwellings identified as having one
      or more Aboriginal person(s) living there at the time of the survey. RESULTS:
      Overall, the 399 interviews from an eligible sample of 691 SA Aboriginal adults
      yielded a response rate of 57.7%. These face-to-face interviews were conducted by
      ten interviewers retained from a total of 27 trained Aboriginal interviewers.
      Challenges were found in three main areas: identification and recruitment of
      participants; interviewer recruitment and retainment; and using appropriate
      engagement with communities. These challenges were resolved, or at least mainly
      overcome, by following local protocols with communities and their
      representatives, and reaching agreement on the process of research for Aboriginal
      people. CONCLUSIONS: Obtaining a representative sample of Aboriginal participants
      in a culturally appropriate way was methodologically challenging and required
      high levels of commitment and resources. Adhering to these principles has
      resulted in a rich and unique data set that provides an overview of the self
      reported health status for Aboriginal people living in South Australia. This
      process provides some important principles to be followed when engaging with
      Aboriginal people and their communities for the purpose of health research.

PMID- 25986554
TI  - Low-intensity pulsed ultrasound for treating delayed union scaphoid fractures:
      case series.
AB  - BACKGROUND: The standard treatment to enhance fracture healing of scaphoid
      nonunions is surgery. Low-intensity pulsed ultrasound (LIPUS) is gaining in
      popularity as an alternative treatment to improve fracture healing; however,
      little is known about success rates of this treatment in scaphoid-delayed unions.
      The purpose of our study is to define the success rate of LIPUS treatment for
      delayed union of scaphoid fractures and further analyze whether initial
      management or fracture type influences success rate. METHODS: During the period
      of 2011-2013, in the central orthopedic clinic of our institution, patients
      diagnosed with delayed union of the scaphoid were offered with LIPUS treatment as
      an alternative to conventional surgical treatment. These patients were then
      divided into subgroups according to the time elapsed from initial injury until
      diagnosis of the fracture. RESULTS: Overall, 22 of 29 (76%) fractures healed, 12
      of 13 (92%) of the early diagnosed group, and 10 of 16 (63%) of the late
      diagnosed group. Difference in healing rate between proximal pole, waist, and
      distal pole fractures was not statistically significant. CONCLUSION: LIPUS can
      help heal delayed union scaphoid fractures, especially in fractures diagnosed and
      treated soon after injury and may serve as an alternative to surgical treatment.

PMID- 25986555
TI  - Letter to the editor regarding "Situs inversus with levocardia, infrahepatic
      interruption of the inferior vena cava, and azygos continuation: a case report".

PMID- 25986557
TI  - Infanticide as sexual conflict: coevolution of male strategies and female
      counterstrategies.
AB  - One of the earliest recognized forms of sexual conflict was infanticide by males,
      which imposes serious costs on female reproductive success. Here I review two
      bodies of evidence addressing coevolved strategies of males and females. The
      original sexual selection hypothesis arguing that infanticide improves male
      mating success by accelerating the return of females to fertilizable condition
      has been generally supported in some taxa--notably, some primates, carnivores,
      rodents, and cetaceans--but not in other taxa. One result of recent research has
      been to implicate other selective benefits of infanticide by males in various
      taxa from insects to birds to mammals, such as acquisition of breeding status or
      improvement of the female breeding condition. In some cases, however, the
      adaptive significance of male infanticide remains obscure. The second body of
      data I review is arguably the most important result of recent research:
      clarifying the possible female counterstrategies to infanticide. These potential
      counterstrategies span diverse biological systems, ranging from sexual behavior
      (e.g., polyandrous mating), to physiology (e.g., the Bruce effect), to individual
      behavior (e.g., maternal aggression), to social strategies (e.g., association
      with coalitionary defenders of either sex). Although much remains to be studied,
      these current data provide compelling evidence of sexually antagonistic
      coevolution surrounding the phenomenon of infanticide.

PMID- 25986556
TI  - Glia Disease and Repair-Remyelination.
AB  - The inability of the mammalian central nervous system (CNS) to undergo
      spontaneous regeneration has long been regarded as a central tenet of
      neurobiology. However, although this is largely true of the neuronal elements of
      the adult mammalian CNS, save for discrete populations of granular neurons, the
      same is not true of its glial elements. In particular, the loss of
      oligodendrocytes, which results in demyelination, triggers a spontaneous and
      often highly efficient regenerative response, remyelination, in which new
      oligodendrocytes are generated and myelin sheaths are restored to denuded axons.
      Yet, remyelination in humans is not without limitation, and a variety of
      demyelinating conditions are associated with sustained and disabling myelin loss.
      In this review, we will review the biology of remyelination, including the cells
      and signals involved; describe when remyelination occurs and when and why it
      fails and the consequences of its failure; and discuss approaches for
      therapeutically enhancing remyelination in demyelinating diseases of both
      children and adults, both by stimulating endogenous oligodendrocyte progenitor
      cells and by transplanting these cells into demyelinated brain. 

PMID- 25986559
TI  - Plasmodium falciparum Plasmepsin V (PfPMV): Insights into recombinant expression,
      substrate specificity and active site structure.
AB  - Plasmepsin V from Plasmodium falciparum (PfPMV) is responsible for the cleavage
      of the Plasmodium export element (PEXEL) motif at the N-terminus of several
      hundreds of the exported proteins. PfPMV is necessary for parasite viability and
      has become a novel promising target for antimalarial therapy. The first
      recombinant expression of soluble, active PfPMV as thioredoxin fusion proteins is
      reported herein. Two truncated forms of PfPMV were fused to thioredoxin (Trx) to
      generate Trx-PfPMVp37 and Trx-PfPMVm84. The fusion proteins were successfully
      purified using Ni(2+) affinity chromatography in combination with ATP treatment
      to eliminate Escherichia coli HSP60 contaminant. Trx-PfPMVm84 could hydrolyze the
      PEXEL-containing peptides more efficiently than Trx-PfPMVp37. Interestingly, both
      Trx-PfPMVs preferred to cleave PfEMP2 peptide over HRPII peptide. The replacement
      of Ser with Val or Glu at P1' position created a substrate with 75% reduction in
      the enzyme activity, whereas the substitution of Ile with Lys or Glu at P2
      position reduced the cleavage efficiency by 30%. The activity of Trx-PfPMVm84 was
      inhibited by PMSF and nelfinavir but not by pepstatin A. After the removal of Trx
      domain, activities of both enzymes toward PfEMP2 and HRPII peptides were fitted
      to the Michaelis-Menten model to determine kinetic parameters. The Km values
      toward both peptides were apparently much lower than the previously reported data
      although with similar kcat values. Along with an improved PfPMV preparation
      protocol, these findings have provided insights into its substrate specificity at
      P2 and P1' positions as well as interactions among the enzyme, substrates, and
      inhibitors. 

PMID- 25986561
TI  - The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases.
AB  - Peptidyl prolyl isomerases (PPIases) are proteins belonging to the immunophilin
      family and are characterised by their cis-trans isomerization activity at the X
      Pro peptide bond, in addition to their tetratricopeptide repeat (TPR) domain,
      important for interaction with the molecular chaperone, Hsp90. Due to this unique
      structure these proteins are able to facilitate protein-protein interactions
      which can impact significantly on a range of cellular processes such as cell
      signalling, differentiation, cell cycle progression, metabolic activity and
      apoptosis. Malfunction and/or dysregulation of most members of this class of
      proteins promotes cellular damage and tissue/organ failure, predisposing to
      ageing and age-related diseases. Many individual genes within the PPIase family
      are associated with several age-related diseases including cardiovascular
      diseases (CVDs), atherosclerosis, type II diabetes mellitus (T2D), chronic kidney
      disease (CDK), neurodegeneration, cancer and age-related macular degeneration
      (AMD), in addition to the ageing process itself. This review will focus on the
      different roles of PPIases, and their therapeutic/ biomarker potential in these
      age-related vascular diseases. 

PMID- 25986560
TI  - Does vegetation complexity affect host plant chemistry, and thus multitrophic
      interactions, in a human-altered landscape?
AB  - Anthropogenic land use may shape vegetation composition and affect trophic
      interactions by altering concentrations of host plant metabolites. Here, we
      investigated the hypotheses that: (1) plant N and defensive secondary metabolite
      contents of the herb Plantago lanceolata are affected by land use intensity (LUI)
      and the surrounding vegetation composition (=plant species richness and P.
      lanceolata density), and that (2) changes in plant chemistry affect abundances of
      the herbivorous weevils Mecinus pascuorum and Mecinus labilis, as well as their
      larval parasitoid Mesopolobus incultus, in the field. We determined plant species
      richness, P. lanceolata density, and abundances of the herbivores and the
      parasitoid in 77 grassland plots differing in LUI index in three regions across
      Germany. We also measured the N and secondary metabolite [the iridoid glycosides
      (IGs) aucubin and catalpol] contents of P. lanceolata leaves. Mixed-model
      analysis revealed that: (1) concentrations of leaf IGs were positively correlated
      with plant species richness; leaf N content was positively correlated with the
      LUI index. Furthermore: (2) herbivore abundance was not related to IG
      concentrations, but correlated negatively with leaf N content. Parasitoid
      abundance correlated positively only with host abundance over the three regions.
      Structural equation models revealed a positive impact of IG concentrations on
      parasitoid abundance in one region. We conclude that changes in plant chemistry
      due to land use and/or vegetation composition may affect higher trophic levels
      and that the manifestation of these effects may depend on local biotic or abiotic
      features of the landscape. 

PMID- 25986558
TI  - Recombination, Pairing, and Synapsis of Homologs during Meiosis.
AB  - Recombination is a prominent feature of meiosis in which it plays an important
      role in increasing genetic diversity during inheritance. Additionally, in most
      organisms, recombination also plays mechanical roles in chromosomal processes,
      most notably to mediate pairing of homologous chromosomes during prophase and,
      ultimately, to ensure regular segregation of homologous chromosomes when they
      separate at the first meiotic division. Recombinational interactions are also
      subject to important spatial patterning at both early and late stages.
      Recombination-mediated processes occur in physical and functional linkage with
      meiotic axial chromosome structure, with interplay in both directions, before,
      during, and after formation and dissolution of the synaptonemal complex (SC), a
      highly conserved meiosis-specific structure that links homolog axes along their
      lengths. These diverse processes also are integrated with recombination
      independent interactions between homologous chromosomes, nonhomology-based
      chromosome couplings/clusterings, and diverse types of chromosome movement. This
      review provides an overview of these diverse processes and their
      interrelationships. 

PMID- 25986562
TI  - Cyclophilin function in Cancer; lessons from virus replication.
AB  - Cyclophilins belong to a group of proteins that possess peptidyl prolyl isomerase
      activity and catalyse the cis-trans conversion of proline peptide bonds.
      Cyclophilin members play important roles in protein folding and as molecular
      chaperones, in addition to a well-established role as host factors required for
      completion of the virus life cycle. Members of the cyclophilin family are
      overexpressed in a range of human malignancies including hepatocellular cancer,
      pancreatic cancer, nonsmall cell lung cancer, gastric cancer, colorectal cancer
      and glioblastoma multiforme, however, their precise role in tumourigenesis
      remains unclear. In recent years, mounting evidence supports a role for prolyl
      isomerisation during mammalian cell division; a process with striking similarity
      to plasma membrane remodelling during virus replication. Here, we summarise our
      current understanding of the role of cyclophilins in cancer. We review the
      function of cyclophilins during mammalian cell division and during HIV-1
      infection, and highlight common processes involving members of the ESCRT and Rab
      GTPase families. 

PMID- 25986563
TI  - Molecular Aspects of FKBP51 that Enable Melanoma Dissemination.
AB  - FKBP51 (FKBP5 Official Symbol) is large molecular weight member of the FK506
      binding protein family, a subfamily of the immunophilin proteins. FKBP51 exerts
      multiple biological functions in the cell, including modulation of steroid
      hormone response, immune regulation, cell proliferation, regulation of pAkt
      levels and control of NF-kappaB activation. Several lines of evidence support a
      role for this protein in cancer biology, especially in resistance to chemo- and
      radio-therapy. Recent research studies highlighted functions of FKBP51 in
      promoting the epithelial to mesenchymal transition (EMT) transdifferentiation
      program in melanoma. This process, which is classically regulated by Transforming
      Growth Factor (TGF)-beta, enables cancer cells to disseminate from primary tumors
      and spread to distant locations, acquiring resistance to therapy and self-renewal
      capability. This last, in turn, is crucial to their subsequent expansion at sites
      of dissemination. The aim of the present article is to review recent literature
      data that involve FKBP51 in the mechanisms that switch the TGF-beta from a tumor
      suppressor to a pro-metastatic invader. 

PMID- 25986564
TI  - The FKBP51-Glucocorticoid Receptor Balance in Stress-Related Mental Disorders.
AB  - The immunophilin FK506 binding protein 51 (FKBP51) has emerged as one of the most
      intensely investigated proteins in stress-related mental disorders. It was
      originally characterized as Hsp90 cochaperone and part of the receptor-chaperone
      heterocomplex that governs the activity of steroid receptors. It turned out that
      the presence of FKBP51 in this heterocomplex leads to diminished activity of the
      corticosteroid receptors. In particular, based on its inhibitory action on the
      glucocorticoid receptor (GR), FKBP51 was included in a candidate gene approach to
      discover gene polymorphisms that might be relevant for the development and
      treatment of major depression. The discovery that polymorphisms in the gene
      coding for FKBP51 were linked to the treatment response of depressed patients
      intensified the research on the role of FKBP51 in stress-related diseases
      worldwide. It has become evident that FKBP51 is not only a regulator of GR
      action, but also a GR target. The function of this ultrashort intracellular
      feedback loop is critically important for cellular and physiological stress
      regulation as it does not only calibrate the function of GR, but also the levels
      of FKBP51. Given the pleiotropic functions of FKBP51, its levels might be equally
      important for mental disorders as GR function and hence for the development of
      potential FKBP51 drug targets. 

PMID- 25986565
TI  - Therapeutic Targeting of the FKBP52 Co-Chaperone in Steroid Hormone Receptor
      Regulated Physiology and Disease.
AB  - Steroid hormone receptors are ligand-dependent transcription factors that require
      the dynamic, ordered assembly of multimeric chaperone complexes to reach a
      functional conformation. Heat shock protein (Hsp) 70 and Hsp90 serve as the
      central chaperones that mediate this process in conjunction with a variety of co
      chaperones. Many of these cochaperones represent potential therapeutic targets
      for the disruption of Hsp90 client protein function. FKBP52 is an Hsp90
      associated co-chaperone that has emerged as a promising therapeutic candidate due
      to its functional specificity for a small subset of Hsp90 client proteins
      including androgen (AR), glucocorticoid (GR), and progesterone (PR) receptors.
      Given its Hsp90-client protein specificity, the targeting of FKBP52 should be
      more specific and less toxic than the Hsp90- targeting drugs. Additionally, the
      fkbp52-deficient mice display specific phenotypes related to androgen,
      progesterone, and glucocorticoid insensitivity suggesting minimal off-target
      effects. Finally, the fact that FKBP52 is already a validated target of the
      clinically approved immunosuppressive drug, FK506 (Tacrolimus), indicates that
      FKBP52 is a "druggable" protein. Thus, the development of FKBP52-specific small
      molecule inhibitors is predicted to be a highly targeted strategy with potential
      for the treatment of any disease that is dependent on a functional AR, GR, and/or
      PR signaling pathway. Much progress has been made in understanding the residues
      and domains critical for FKBP52 function. The proline-rich loop overhanging the
      FKBP52 FK1 catalytic domain is functionally important and likely represents an
      interaction surface within the receptor-chaperone complex. Thus, the targeting of
      FKBP52 proline-rich loop interactions is the most attractive therapeutic approach
      to disrupt FKBP52 regulation of receptor activity in steroid hormone receptor
      dependent physiology and disease. 

PMID- 25986566
TI  - Regulation of NF-kappaB signalling cascade by immunophilins.
AB  - The fine regulation of signalling cascades is a key event required to maintain
      the appropriate functional properties of a cell when a given stimulus triggers
      specific biological responses. In this sense, cumulative experimental evidence
      during the last years has shown that high molecular weight immunophilins possess
      a fundamental importance in the regulation of many of these processes. It was
      first discovered that TPR-domain immunophilins such as FKBP51 and FKBP52 play a
      cardinal role, usually in an antagonistic fashion, in the regulation of several
      members of the steroid receptor family via its interaction with the heat-shock
      protein of 90-kDa, Hsp90. These Hsp90-associated cochaperones form a functional
      unit with the molecular chaperone influencing ligand binding capacity, receptor
      trafficking, and hormone-dependent transcriptional activity. Recently, it was
      demonstrated that the same immunophilins are also able to regulate the NF-kB
      signalling cascade in an Hsp90 independent manner. In this article we analize
      these properties and discuss the relevance of this novel regulatory pathway in
      the context of the pleiotropic actions managed by NF-kB in several cell types and
      tissues. 

PMID- 25986567
TI  - Steroid Receptor-Associated Immunophilins: Candidates for Diverse Drug-Targeting
      Approaches in Disease.
AB  - The steroid receptor-associated TPR cochaperones FKBP51, FKBP52, CyP40 and PP5
      have non-redundant roles in steroid receptor function that impact steroid hormone
      binding affinity, nucleocyoplasmic shuttling and transcriptional activation of
      target genes in a tissue-specific manner. Aberrant expression of these TPR
      immunophilins has the potential to cause steroid-based diseases, including breast
      and prostate cancer, diabetes and metabolic disorders, male and female
      infertility and major depressive and neurodegenerative disorders. This review
      summaries the function of these proteins as cochaperones in steroid receptor
      Hsp90 complexes and elaborates on their role in alternative, Hsp90-dependent and 
      independent signalling pathways not involving steroid receptors. The review also
      extensively covers current knowledge of the link between the steroid receptor
      associated immunophilins and human disease. An improved understanding of their
      mechanisms of action has revealed opportunities for molecular therapies to
      enhance or inhibit cellular processes under their control that contribute both to
      human health and disease. 

PMID- 25986568
TI  - FK506-Binding Proteins and Their Diverse Functions.
AB  - FK506 binding proteins (FKBPs) are a family of highly conserved proteins in
      eukaryotes. The prototype of this protein family, FKBP12, is the binding partner
      for immunosuppressive drugs FK506 and rapamycin. FKBP12 functions as a cis/trans
      peptidyl prolyl isomerase (PPIase) that catalyzes interconversion between prolyl
      cis/trans conformations. Members of the FKBP family contain one or several PPIase
      domains, which do not always exhibit PPIase activity yet are all essential for
      their function. FKBPs are involved in diverse cellular functions including
      protein folding, cellular signaling, apoptosis and transcription. They elicit
      their function through direct binding and altering conformation of their target
      proteins, hence acting as molecular switches. In this review, we provide a
      general summary for the structures and diverse functions of FKBPs found in
      mammalian cells. 

PMID- 25986569
TI  - Immunophilins: Structures, Mechanisms and Ligands.
AB  - Immunophilins consist of a family of highly conserved proteins which possess
      binding abilities to immunosuppressive drugs. Cyclophilins (Cyps) and FK506
      binding proteins (FKBP) are family proteins collectively referred as
      immunophilins. Most Cyps and FKBP family members catalyse peptidyl-prolyl
      cis/trans isomerase (PPIase) mediated reactions and form binary complexes with
      their ligands cyclosporine A and FK506. Immunophilins are also involved in key
      biochemical processes including protein folding, receptor signalling, protein
      trafficking, and transcription and exhibit versatile biological functions, when
      complexed with their ligands. Therapeutic implications of immunophilins and
      effects of their ligands in neurodegenerative disorders, cancer, and infectious
      diseases have been accumulating in recent years. This review focuses on molecular
      characteristics of the canonical and non-canonical immunophilin family members
      from human and Plasmodium falciparum and P. vivax, recent progress on
      immunophilin inhibitor development, and future perspectives of structure-based
      design of non-immunosuppressive immunophilin ligands with potential
      pharmacological activities against infectious diseases. 

PMID- 25986570
TI  - Recent Progress in FKBP Ligand Development.
AB  - FK506-binding proteins have been implicated in numerous human diseases suggesting
      novel therapeutic opportunities. In particular, the large FKBP51 has emerged as
      an important regulator of the stress-coping system and as an established risk
      factor for stress-related disorders. The principal druggabilty of FKBPs is
      evidenced by the prototypical high affinity ligands FK506 and rapamycin but the
      development of more refined and selective chemical probes for FKBPs has been
      challenging. In this review we summarize recent advances in the development of
      FKBP ligands, which cumulated in the first highly selective ligands for FKBP51.
      The best ligand SAFit2 allowed the proof-of-concept in mice for FKBP51 inhibitors
      as potentially novel antidepressants. Finally, we discuss pending issues that
      need to be addressed for the further development of FKBP51-directed drugs. 

PMID- 25986572
TI  - Exploring demographic and lifestyle associations with patient experience
      following telephone triage by a primary care doctor or nurse: secondary analyses
      from a cluster randomised controlled trial.
AB  - BACKGROUND: The ESTEEM trial was a cluster randomised controlled trial that
      compared two telephone triage management systems (general practitioner (GP) or a
      nurse supported by computer decision support software) with usual care, in
      response to a request for same-day consultation in general practice. AIM: To
      investigate associations between trial patients' demographic, health, and
      lifestyle characteristics, and their reported experiences of care. SETTING:
      Recruitment of 20 990 patients occurred between May 2011 and December 2012 in 42
      GP practices in England (13 GP triage, 15 nurse triage, 14 usual care). METHOD:
      Patients reported their experiences via a postal questionnaire issued 4 weeks
      after their initial request for a same-day consultation. Overall satisfaction,
      ease of accessing medical help/advice, and convenience of care were analysed
      using linear hierarchical modelling. RESULTS: Questionnaires were returned by 12
      132 patients (58%). Older patients reported increased overall satisfaction
      compared with patients aged 25-59 years, but patients aged 16-24 years reported
      lower satisfaction. Compared with white patients, patients from ethnic minorities
      reported lower satisfaction in all three arms, although to a lesser degree in the
      GP triage arm. Patients from ethnic minorities reported higher satisfaction in
      the GP triage than in usual care, whereas white patients reported higher
      satisfaction with usual care. Patients unable to take time away from work or who
      could only do so with difficulty reported lower satisfaction across all three
      trial arms. CONCLUSIONS: Patient characteristics, such as age, ethnicity and
      ability to attend their practice during work hours, were associated with their
      experiences of care following a same-day consultation request in general
      practice. Telephone triage did not increase satisfaction among patients who were
      unable to attend their practice during working hours. TRIAL REGISTRATION NUMBER:
      ISCRTN20687662.

PMID- 25986571
TI  - Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and
      Drug Design.
AB  - Among the 22 FKBP domains in the human genome, FKBP12.6 and the first FKBP
      domains (FK1) of FKBP51 and FKBP52 are evolutionarily and structurally most
      similar to the archetypical FKBP12. As such, the development of inhibitors with
      selectivity among these four FKBP domains poses a significant challenge for
      structure-based design. The pleiotropic effects of these FKBP domains in a range
      of signaling processes such as the regulation of ryanodine receptor calcium
      channels by FKBP12 and FKBP12.6 and steroid receptor regulation by the FK1
      domains of FKBP51 and FKBP52 amply justify the efforts to develop selective
      therapies. In contrast to their close structural similarities, these four FKBP
      domains exhibit a substantial diversity in their conformational flexibility. A
      number of distinct conformational transitions have been characterized for FKBP12
      spanning timeframes from 20 s to 10 ns and in each case these dynamics have been
      shown to markedly differ from the conformational behavior for one or more of the
      other three FKBP domains. Protein flexibilitybased inhibitor design could draw
      upon the transitions that are significantly populated in only one of the targeted
      proteins. Both the similarities and differences among these four proteins
      valuably inform the understanding of how dynamical effects propagate across the
      FKBP domains as well as potentially how such intramolecular transitions might
      couple to the larger scale transitions that are central to the signaling
      complexes in which these FKBP domains function. 

PMID- 25986577
TI  - Childhood sexual violence in Zimbabwe: evidence for the epidemic against girls.
AB  - Sexual abuse during childhood is a public health and human rights concern
      throughout the world, including Sub-Saharan Africa. In 2011, Zimbabwe initiated
      national prevalence data collection on violence against children to inform
      government policy and programs. We interviewed 567 females and 589 males, aged 18
      24 years following standardized and previously tested survey methods from the
      region. Of females 32.5%, and of males 8.9%, reported experiencing sexual
      violence before age 18. Most female (62.7%) and male (47.9%) victims of sexual
      violence experienced more than one incident of sexual violence prior to age 18
      years. Three in four females (77.7%) and one in four males (26.7%) of those who
      experienced sexual violence reported that the first incident was perpetrated by a
      boyfriend or girlfriend. Few victims received professional help (2.7% of females
      and 2.4% of males who had reported experiencing sexual violence). Violence
      against girls is at epidemic levels in Zimbabwe. Most sexual violence against
      girls occurs within the context of peer relationships. Child victims who seek
      potentially life-saving support tend not to receive it. This study is evidence of
      a national public health and child rights emergency in the country and a case for
      increased, longer-term investment by the government and its development partners
      in policy reform for enhancing adolescent girls' empowerment and protection. 

PMID- 25986578
TI  - Chemomodulating Effects of Flavonoids in Human Leukemia Cells.
AB  - Flavonoids, a diverse class of polyphenolic compounds, are well known for their
      anticancer properties. Moreover, it is generally accepted that these plant
      secondary metabolites can also sensitize malignant cells to conventional
      chemotherapeutic drugs and could thus be considered as potential adjunctive
      agents in cancer treatment. In this review article we show that besides
      potentiating the anticancer activity of standard chemotherapeutics by modifying
      the molecular events that are involved in cell growth, differentiation and
      apoptosis, flavonoids might also act as inhibitory modulators in human leukemia
      cells. The specific behavior of a certain flavonoid in such combination
      treatments is multifactorial being dependent on various aspects, including
      cellular context, molecular mechanisms of clinical drugs, temporal regimen of
      administration, as well as doses of agents. Based on the highly complex nature of
      leukemogenesis it is feasible that a multifaceted therapeutic approach is also
      required to cure this disease and therefore, combined chemotherapeutic schemes
      incorporating natural plant metabolites as chemosensitizing agents can represent
      a new attractive strategy for more successful treatment of leukemia patients in
      the future. However, as highlighted in this review, caution should be taken when
      affecting malignant cells concurrently with chemotherapeutic drugs and flavonoids
      as unwisely chosen combinations can lead to inadvisable results and sometimes
      even deteriorate the clinical outcomes. 

PMID- 25986579
TI  - DPP-4 inhibition with linagliptin ameliorates cognitive impairment and brain
      atrophy induced by transient cerebral ischemia in type 2 diabetic mice.
AB  - BACKGROUND: It is unclear whether dipeptidylpeptidase-4 (DPP-4) inhibition can
      counteract the impairment of cognitive function and brain injury caused by
      transient cerebral ischemia in type 2 diabetes. The present study was undertaken
      to test our hypothesis that linagliptin, a DPP-4 inhibitor, administration
      following transient cerebral ischemia can ameliorate cognitive impairment and
      brain injury in diabetic mice. METHODS: db/db mice, a model of obese type 2
      diabetes, were subjected to transient cerebral ischemia by 17 min of bilateral
      common carotid artery occlusion (BCCAO), and were administered (1) vehicle or (2)
      linagliptin for 8 weeks or 1 week. For the long-term experiment on 8 weeks of
      linagliptin treatment, cognitive function, and volume and neuronal cell number of
      hippocampus and cortex were estimated in each group of mice. For the short-term
      experiment on 1 week of linagliptin treatment, cerebral IgG extravasation, Iba-1
      positive cell number (reactive microglia), oxidative stress, and claudin-5 and
      gp91phox protein levels were measured in each group of mice. RESULTS: Linagliptin
      administration almost completely suppressed the circulating DPP-4 activity in
      db/db mice, but did not significantly reduce blood glucose or ameliorate glucose
      intolerance in db/db mice. Linagliptin administration following transient
      cerebral ischemia significantly counteracted cognitive impairment in diabetic
      mice, as estimated by water maze test and passive avoidance test. Linagliptin
      administration ameliorated the decrease in cerebral volume and neuronal cell
      number in hippocampus and cortex of diabetic mice. Linagliptin administration
      significantly reduced the increase in cerebral IgG extravasation and the increase
      in reactive microglia caused by transient cerebral ischemia in diabetic mice.
      Furthermore, linagliptin significantly suppressed the increase in cerebral
      oxidative stress in transient cerebral ischemia-subjected diabetic mice.
      Furthermore, linagliptin significantly increased cerebral claudin-5 and
      significantly decreased gp91phox in diabetic mice subjected to transient cerebral
      ischemia. CONCLUSIONS: DPP-4 inhibition with linagliptin counteracted cognitive
      impairment and brain atrophy induced by transient cerebral ischemia in diabetic
      mice, independently of blood glucose lowering effect. This cerebroprotective
      effect of linagliptin was associated with the suppression of blood-brain barrier
      disruption and the attenuation of cerebral oxidative stress. Thus, our present
      work highlights DPP-4 inhibition as a promising therapeutic strategy for
      cognitive impairment and cerebral vascular complications in type 2 diabetes.

PMID- 25986580
TI  - Improving dengue virus capture rates in humans and vectors in Kamphaeng Phet
      Province, Thailand, using an enhanced spatiotemporal surveillance strategy.
AB  - Dengue is of public health importance in tropical and sub-tropical regions.
      Dengue virus (DENV) transmission dynamics was studied in Kamphaeng Phet Province,
      Thailand, using an enhanced spatiotemporal surveillance of 93 hospitalized
      subjects with confirmed dengue (initiates) and associated cluster individuals
      (associates) with entomologic sampling. A total of 438 associates were enrolled
      from 208 houses with household members with a history of fever, located within a
      200-m radius of an initiate case. Of 409 associates, 86 (21%) had laboratory
      confirmed DENV infection. A total of 63 (1.8%) of the 3,565 mosquitoes collected
      were dengue polymerase chain reaction positive (PCR+). There was a significant
      relationship between spatial proximity to the initiate case and likelihood of
      detecting DENV from associate cases and Aedes mosquitoes. The viral detection
      rate from human hosts and mosquito vectors in this study was higher than
      previously observed by the study team in the same geographic area using different
      methodologies. We propose that the sampling strategy used in this study could
      support surveillance of DENV transmission and vector interactions. 

PMID- 25986581
TI  - Access to care for Chagas disease in the United States: a health systems
      analysis.
AB  - There are 300,000 estimated cases of Chagas disease in the United States but
      limited data on access to care. This study analyzed trends in access to care for
      Chagas disease in the United States and assessed the national and state barriers
      to access. Data on cases in blood donors and drug releases were obtained from the
      AABB (formerly American Association of Blood Banks) and U.S. Centers for Disease
      Control and Prevention (CDC), respectively. Semi-structured in-depth interviews
      were conducted with 30 key informants at the national level and in five states
      where treatment had been released. Interview responses were analyzed according to
      the health systems dimensions of regulation, financing, payment, organization,
      and persuasion. Data indicate that 1,908 cases were identified in the blood
      donation system from 2007 to 2013 and that CDC released 422 courses of
      benznidazole or nifurtimox during this period. The barriers to access at the
      national level include limited diagnostic and institutionalized referral and care
      processes, lack of financing for patient-care activities, and limited awareness
      and training among providers. This study demonstrates that access to treatment of
      Chagas disease in the United States is limited. The lack of licensing is only one
      of several barriers to access, highlighting the need for a health systems
      perspective when scaling up access to these essential medicines. 

PMID- 25986582
TI  - Fecal virome analysis of three carnivores reveals a novel nodavirus and multiple
      gemycircularviruses.
AB  - BACKGROUND: More knowledge about viral populations in wild animals is needed in
      order to better understand and assess the risk of zoonotic diseases. In this
      study we performed viral metagenomic analysis of fecal samples from three healthy
      carnivores: a badger (Meles meles), a mongoose (Herpestes ichneumon) and an otter
      (Lutra lutra) from Portugal. RESULTS: We detected the presence of novel highly
      divergent viruses in the fecal material of the carnivores analyzed, such as five
      gemycircularviruses. Four of these gemycircularviruses were found in the mongoose
      and one in the badger. In addition we also identified an RNA-dependent RNA
      polymerase gene from a putative novel member of the Nodaviridae family in the
      fecal material of the otter. CONCLUSIONS: Together these results underline that
      many novel viruses are yet to be discovered and that fecal associated viruses are
      not always related to disease. Our study expands the knowledge of viral species
      present in the gut, although the interpretation of the true host species of such
      novel viruses needs to be reviewed with great caution.

PMID- 25986584
TI  - Cutaneous penetration of soft nanoparticles via photodamaged skin: Lipid-based
      and polymer-based nanocarriers for drug delivery.
AB  - Photoaging is recognized as the factor damaging skin-barrier function. The aim of
      this study was to examine the impact of ultraviolet (UV) irradiation on the
      cutaneous penetration of soft nanoparticles, including nanostructured lipid
      carriers (NLCs) and poly(lactic-co-glycolic acid) polymer nanoparticles (PNs). In
      vitro cutaneous permeation of retinoic acid (RA) carried by nanoparticles was
      evaluated. In vivo nude mouse skin distribution of topically applied
      nanoparticles was observed by fluorescence and confocal microscopies. The
      association of nanoparticles with cultured keratinocytes was measured by flow
      cytometry and fluorescence microscopy. The average diameter and surface charge
      were 236nm and -32mV for NLCs, and 207nm and -12mV for PNs. The ultrastructural
      images of skin demonstrated that the application of UV produced a loss of Odland
      bodies and desmosomes, the organelles regulating skin-barrier function. UVA
      exposure increased skin deposition of RA regardless of nanoparticle formulation.
      UVB did not alter RA deposition from nanoparticles as compared to the non-treated
      group. Exposure to UVA promoted RA delivery into hair follicles from NLCs and PNs
      by 4.2- and 4.9-fold, respectively. The in vivo skin distribution also showed a
      large accumulation of Nile red-loaded nanoparticles in follicles after UVA
      treatment. The soft nanoparticles were observed deep in the dermis. PNs with
      higher lipophilicity showed a greater association with keratinocytes compared to
      NLCs. The cell association of PNs was increased by UVA application, whereas the
      association between NLCs and keratinocytes was reduced two times by UVA. It was
      concluded that both follicles and intercellular spaces were the main pathways for
      nanoparticle diffusion into photodamaged skin. 

PMID- 25986583
TI  - Partial protein domains: evolutionary insights and bioinformatics challenges.
AB  - Protein domains are generally thought to correspond to units of evolution. New
      research raises questions about how such domains are defined with bioinformatics
      tools and sheds light on how evolution has enabled partial domains to be viable. 

PMID- 25986585
TI  - The genetics of age-related macular degeneration (AMD)--Novel targets for
      designing treatment options?
AB  - Age-related macular degeneration (AMD) is a progressive disease of the central
      retina and the main cause of legal blindness in industrialized countries. Risk to
      develop the disease is conferred by both individual as well as genetic factors
      with the latter being increasingly deciphered over the last decade.
      Therapeutically, striking advances have been made for the treatment of the
      neovascular form of late stage AMD while for the late stage atrophic form of the
      disease, which accounts for almost half of the visually impaired, there is
      currently no effective therapy on the market. This review highlights our current
      knowledge on the genetic architecture of early and late stage AMD and explores
      its potential for the discovery of novel, target-guided treatment options. We
      reflect on current clinical and experimental therapies for all forms of AMD and
      specifically note a persisting lack of efficacy for treatment in atrophic AMD. We
      further explore the current insight in AMD-associated genes and pathways and
      critically question whether this knowledge is suited to design novel treatment
      options. Specifically, we point out that known genetic factors associated with
      AMD govern the risk to develop disease and thus may not play a role in its
      severity or progression. Treatments based on such knowledge appear appropriate
      rather for prevention than treatment of manifest disease. As a consequence,
      future research in AMD needs to be greatly focused on approaches relevant to the
      patients and their medical needs. 

PMID- 25986586
TI  - Nitroxide delivery system for Nrf2 activation and skin protection.
AB  - Cyclic nitroxides are a large group of compounds composed of diverse stable
      radicals also known as synthetic antioxidants. Although nitroxides are valuable
      for use in several skin conditions, in in vivo conditions they have several
      drawbacks, such as nonspecific dispersion in normal tissue, preferential renal
      clearance and rapid reduction of the nitroxide to the corresponding
      hydroxylamine. However, these drawbacks can be easily addressed by encapsulating
      the nitroxides within microemulsions. This approach would allow nitroxide
      activity and therefore their valuable effects (e.g. activation of the Keap1-Nrf2
      EpRE pathway) to continue. In this work, nitroxides were encapsulated in a
      microemulsion composed of biocompatible ingredients. The nanometric size and
      shape of the vehicle microemulsion and nitroxide microemulsion displayed high
      similarity, indicating that the stability of the microemulsions was preserved.
      Our studies demonstrated that nitroxide microemulsions were more potent inducers
      of the Keap1-Nrf2-EpRE pathway than the free nitroxides, causing the activation
      of phase II enzymes. Moreover, microemulsions containing nitroxides significantly
      reduced UVB-induced cytotoxicity in the skin. Understanding the mechanism of this
      improved activity may expand the usage of many other Nrf2 modulating molecules in
      encapsulated form, as a skin protection strategy against oxidative stress-related
      conditions. 

PMID- 25986588
TI  - Probing the interaction of nanoparticles with mucin for drug delivery
      applications using dynamic light scattering.
AB  - Drug delivery via the eye, nose, gastrointestinal tract and lung is of great
      interest as they represent patient-compliant and facile methods to administer
      drugs. However, for a drug to reach the systemic circulation it must penetrate
      the "mucus barrier". An understanding of the characteristics of the mucus barrier
      is therefore important in the design of mucus penetrating drug delivery vehicles
      e.g. nanoparticles. Here, a range of nanoparticles - silica, aluminium coated
      silica, poly (lactic-co-glycolic acid) (PLGA) and PEGylated PLGA - each with
      known but different physicochemical characteristics were examined in the presence
      of mucin to identify those characteristics that engender nanoparticle/mucin
      interactions and thus, to define "design rules" for mucus penetrating
      (nano)particles (MPP), at least in terms of the surface characteristics of charge
      and hydrophilicity. Dynamic light scattering (DLS) and rheology have been used to
      assess the interaction between such nanoparticles and mucin. It was found that
      negatively charged and hydrophilic nanoparticles do not exhibit an interaction
      with mucin whereas positively charged and hydrophobic nanoparticles show a strong
      interaction. Surface grafted poly (ethylene glycol) (PEG) chains significantly
      reduced this interaction. This study clearly demonstrates that the established
      colloid science techniques of DLS and rheology are very powerful screening tools
      to probe nanoparticle/mucin interactions. 

PMID- 25986587
TI  - Optimization of controlled release nanoparticle formulation of verapamil
      hydrochloride using artificial neural networks with genetic algorithm and
      response surface methodology.
AB  - This study was performed to optimize the formulation of polymer-lipid hybrid
      nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil
      hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling
      and optimization were conducted based on a spherical central composite design.
      Three formulation factors, i.e., weight ratio of drug to lipid (X1), and
      concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent
      variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were
      selected as dependent variables. The predictive performance of artificial neural
      networks (ANN) and the response surface methodology (RSM) were compared. As ANN
      was found to exhibit better recognition and generalization capability over RSM,
      multi-objective optimization of PLN was then conducted based upon the validated
      ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high
      drug loading efficiency (92.4%, w/w) and a small mean particle size (~100nm). The
      predicted response variables matched well with the observed results. The three
      formulation factors exhibited different effects on the properties of PLN. ANN in
      coordination with continuous GA represent an effective and efficient approach to
      optimize the PLN formulation of VRP with desired properties. 

PMID- 25986589
TI  - A New Method for Automated Identification and Morphometry of Myelinated Fibers
      Through Light Microscopy Image Analysis.
AB  - Nerve morphometry is known to produce relevant information for the evaluation of
      several phenomena, such as nerve repair, regeneration, implant, transplant,
      aging, and different human neuropathies. Manual morphometry is laborious,
      tedious, time consuming, and subject to many sources of error. Therefore, in this
      paper, we propose a new method for the automated morphometry of myelinated fibers
      in cross-section light microscopy images. Images from the recurrent laryngeal
      nerve of adult rats and the vestibulocochlear nerve of adult guinea pigs were
      used herein. The proposed pipeline for fiber segmentation is based on the
      techniques of competitive clustering and concavity analysis. The evaluation of
      the proposed method for segmentation of images was done by comparing the
      automatic segmentation with the manual segmentation. To further evaluate the
      proposed method considering morphometric features extracted from the segmented
      images, the distributions of these features were tested for statistical
      significant difference. The method achieved a high overall sensitivity and very
      low false-positive rates per image. We detect no statistical difference between
      the distribution of the features extracted from the manual and the pipeline
      segmentations. The method presented a good overall performance, showing
      widespread potential in experimental and clinical settings allowing large-scale
      image analysis and, thus, leading to more reliable results. 

PMID- 25986591
TI  - Protecting Trade Secrets in Canada.
AB  - Patents in the life sciences industries are a key form of intellectual property
      (IP), particularly for products such as brand-name drugs and medical devices.
      However, trade secrets can also be a useful tool for many types of innovations.
      In appropriate cases, trade secrets can offer long-term protection of IP for a
      lower financial cost than patenting. This type of protection must be approached
      with caution as there is little room for error when protecting a trade secret.
      Strong agreements and scrupulous security can help to protect the secret. Once a
      trade secret is disclosed to the public, it cannot be restored as the owner's
      property; however, if the information is kept from the public domain, the owner
      can have a property right of unlimited duration in the information. In some
      situations patents and trade secrets may be used cooperatively to protect
      innovation, particularly for manufacturing processes. 

PMID- 25986590
TI  - Does lithium reduce acute suicidal ideation and behavior? A protocol for a
      randomized, placebo-controlled multicenter trial of lithium plus Treatment As
      Usual (TAU) in patients with suicidal major depressive episode.
AB  - BACKGROUND: Lithium has proven suicide preventing effects in the long-term
      treatment of patients with affective disorders. Clinical evidence from case
      reports indicate that this effect may occur early on at the beginning of lithium
      treatment. The impact of lithium treatment on acute suicidal thoughts and/or
      behavior has not been systematically studied in a controlled trial. The primary
      objective of this confirmatory study is to determine the association between
      lithium therapy and acute suicidal ideation and/or suicidal behavior in
      inpatients with a major depressive episode (MDE, unipolar and bipolar disorder
      according to DSM IV criteria). The specific aim is to test the hypothesis that
      lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a
      significantly greater decrease in suicidal ideation and/or behavior over 5 weeks
      in inpatients with MDE. METHODS/DESIGN: We initiated a randomized, placebo
      controlled multicenter trial. Patients with the diagnosis of a moderate to severe
      depressive episode and suicidal thoughts and/or suicidal behavior measured with
      the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add
      lithium or placebo to their treatment as usual. Change in the clinician
      administered S-STS from the initial to the final visit will be the primary
      outcome. DISCUSSION: There is an urgent need to identify treatments that will
      acutely decrease suicidal ideation and/or suicidal behavior. The results of this
      study will demonstrate whether lithium reduces suicidal ideation and behavior
      within the first 5 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT02039479.

PMID- 25986594
TI  - Solid-State and Solution Characterization of Myricetin.
AB  - Myricetin (MYR) is a natural compound that has been investigated as a
      chemopreventative agent. MYR has been shown to suppresses ultraviolet B (UVB)
      induced cyclooxygenase-2 (COX-2) protein expression and reduce the incidence of
      UVB-induced skin tumors in mice. Despite MYR's promise as a therapeutic agent,
      minimal information is available to guide the progression of formulations
      designed for future drug development. Here, data is presented describing the
      solid-state and solution characterization of MYR. Investigation into the solid
      state properties of MYR identified four different crystal forms, two hydrates
      (MYR I and MYR II) and two metastable forms (MYR IA and MYR IIA). From solubility
      studies, it was evident that all forms are very insoluble (<5 MUg/ml) in pure
      water. MYR I was found to be the most stable form at 23, 35, and 56 degrees C.
      Stability determination indicated that MYR undergoes rapid apparent first-order
      degradation under basic pH conditions, and that degradation was influenced by
      buffer species. Apparent first-order degradation was also seen when MYR was
      introduced to an oxidizing solution. Improved stability was achieved after
      introducing 0.1% antioxidants to the solution. MYR was found to have good
      stability following exposure to ultraviolet radiation (UVR), which is a
      consideration for topical applications. Finally, a partitioning study indicated
      that MYR possess a log P of 2.94 which, along with its solid-state properties,
      contributes to its poor aqueous solubility. Both the solid-state properties and
      solution stability of MYR are important to consider when developing future
      formulations.

PMID- 25986592
TI  - Host-Directed Therapies for Tuberculosis.
AB  - Host-directed therapies are a relatively new and promising approach to treatment
      of tuberculosis. Modulation of specific host immune pathways, including those
      that impact inflammation and immunopathology, can limit mycobacterial infection
      and pathology, both in cell culture and in animal models. This review explores a
      range of host pathways and drugs, some already approved for clinical use that
      have the potential to provide new adjunctive therapies for tuberculosis. Drugs
      targeting host processes may largely avoid the development of bacterial
      antibiotic resistance, a major public health concern for tuberculosis. However,
      these drugs may also have generally increased risk for side effects on the host.
      Understanding the specific mechanisms by which these drugs act and the
      relationship of these mechanisms to Mycobacterium tuberculosis pathogenesis will
      be critical in selecting appropriate host-directed therapy. Overall, these host
      directed compounds provide a novel strategy for antituberculosis therapy. 

PMID- 25986593
TI  - MicroRNA in Ovarian Biology and Disease.
AB  - MicroRNAs (miRNAs) are posttranscriptional gene regulatory molecules that show
      regulated expression within ovarian tissue. Most research investigating miRNAs in
      the ovary has relied exclusively on in vitro analyses. In this review, we
      highlight those few studies in which investigators have illustrated an in vivo
      effect of miRNAs on ovarian function. We also provide a synopsis of how these
      small noncoding RNAs can impact ovarian disease. miRNAs have great potential as
      novel diagnostic biomarkers for the detection of ovarian disease and in the
      assisted reproductive technologies (ART) for selection of healthy viable oocytes
      and embryos. 

PMID- 25986595
TI  - Assessing the In Vitro Drug Release from Lipid-Core Nanocapsules: a New Strategy
      Combining Dialysis Sac and a Continuous-Flow System.
AB  - The in vitro assessment of drug release from polymeric nanocapsules suspensions
      is one of the most studied parameters in the development of drug-loaded
      nanoparticles. Nevertheless, official methods for the evaluation of drug release
      from submicrometric carriers are not available. In this work, a new approach to
      assess the in vitro drug release profile from drug-loaded lipid-core nanocapsules
      (LNC) was proposed. A continuous-flow system (open system) was designed to
      evaluate the in vitro drug release profiles from different LNC formulations
      containing prednisolone or clobetasol propionate (LNC-CP) as drug model (LNC-PD)
      using a homemade apparatus. The release medium was constantly renewed throughout
      the experiment. A dialysis bag containing 5 mL of formulation (0.5 mg mL(-1)) was
      maintained inside the apparatus, under magnetic stirring and controlled
      temperature (37 degrees C). In parallel, studies based on the conventional
      dialysis sac technique (closed system) were performed. It was possible to
      discriminate the in vitro drug release profile of different formulations using
      the open system. The proposed strategy improved the sink condition, by constantly
      renewing the release medium, thus maintaining the drug concentration farther from
      the saturated concentration in the release medium. Moreover, problems due to
      sampling errors can be easily overcome using this semi-automated system, since
      the collection is done automatically without interference from the analyst. The
      system proposed in this paper brings important methodological and analytical
      advantages, becoming a promising prototype semi-automated apparatus for
      performing in vitro drug release studies from drug-loaded lipid-core nanocapsules
      and other related nanoparticle drug delivery systems.

PMID- 25986596
TI  - Transcutaneous Peptide Immunotherapy of Japanese Cedar Pollinosis Using Solid-in
      Oil Nanodispersion Technology.
AB  - Peptide immunotherapy is an attractive approach to relieve allergic symptoms such
      as rhinitis and asthma. Treatment of Japanese cedar pollinosis (Cryptomeria
      japonica; Cj), from which over one quarter of Japanese population suffer, is
      becoming a great concern. Recently, oral feeding of a peptide (7crp) consisting
      of seven immunodominant human T cell epitopes derived from two enzymes present in
      Cj pollen was demonstrated to have a benefit in treating Cj pollinosis. In this
      work, we aimed to apply a novel transcutaneous administration system as a simple
      and easy peptide delivery for an immunotherapy using a T cell epitope peptide. A
      modified 7crp peptide (7crpR) which contained triarginine linkers between each
      epitopes was designed to increase water solubility and was encapsulated in a
      unique solid-in-oil (S/O) nanodispersion. The S/O nanodispersion consists of a
      nano-sized peptide-surfactant complex dispersed in an oil vehicle. The S/O
      nanopartilces having an average diameter of 230 nm facilitated the permeation of
      the peptide 7crpR into the skin and suppressed serum total IgE and antigen
      specific IgE levels in a Cj pollinosis mouse model. Transcutaneous administration
      of the T cell epitope peptide using the S/O nanodispersion system has potential
      for future simple and easy immunotherapy of Cj pollinosis.

PMID- 25986597
TI  - Effect of Simultaneous Administration of Dihydroxyacetone on the Diffusion of
      Lawsone Through Various In Vitro Skin Models.
AB  - Unprotected sunlight exposure is a risk factor for a variety of cutaneous
      cancers. Topically used dihydroxyacetone (DHA) creates, via Maillard reaction,
      chemically fixed keratin sunscreen in the stratum corneum with significant
      protection against UVA/Soret radiation. When used in conjunction with
      naphthoquinones a naphthoquinone-modified DHA Maillard reaction is produced that
      provides protection across the UVB/UVA/Soret spectra lasting up to 1 week,
      resisting sweating and contact removal. The aim of this study was to examine a
      simplified version of this formulation for effect on UV transmission and to
      determine if penetration levels merit toxicity concerns. Permeability was
      demonstrated for freshly prepared DHA (30 mg/mL) and lawsone (0.035 mg/mL) alone
      and in combination using a side-by-side diffusion apparatus at 37 degrees C over
      48 h across shed snake skin and dermatomed pig skin. These samples were then
      examined for effectiveness and safety. Concentrations were determined by HPLC and
      UPLC monitored from 250-500 nm. Lawsone flux significantly decreased across pig
      skin (20.8 (+/- 4.8) and 0.09 (+/- 0.1) mg/cm(2) h without and with DHA,
      respectively) but did not change across shed snake skin in the presence of DHA.
      Significantly reduced lawsone concentration was noted in donor chambers of
      combined solutions. Damage was not observed in any skins. Darker coloration with
      greater UV absorbance was observed in skins exposed to the combined solution
      versus individual solutions. This study confirmed that combined DHA and lawsone
      provided effective blocking of ultraviolet light through products bound in
      keratinized tissue. DHA permeation levels in pig skin suggest further in vitro
      and in vivo study is required to determine the safety of this system.

PMID- 25986598
TI  - Platelets and diabetes mellitus.
AB  - Platelet activation plays a key role in atherothrombosis in type 2 diabetes
      mellitus (T2DM) and increased in vivo platelet activation with enhanced
      thromboxane (TX) biosynthesis has been reported in patients with impairment of
      glucose metabolism even in the earlier stages of disease and in the preclinical
      phases. In this regards, platelets appear as addresses and players carrying and
      transducing metabolic derangement into vascular injury. The present review
      critically addresses key pathophysiological aspects including (i) hyperglycemia,
      glycemic variability and insulin resistance as determinants and predictors of
      platelet activation, (ii) inflammatory mediators derived from platelets, such as
      soluble CD40 ligand, soluble CD36, Dickkopf-1 and probably soluble receptor for
      advanced glycation-end-products (sRAGE), which expand the functional repertoire
      of platelets from players of hemostasis and thrombosis to powerful amplifiers of
      inflammation by promoting the release of cytokines and chemokines, cell
      activation, and cell-cell interactions; (iii) molecular mechanisms underpinning
      the less-than-expected antithrombotic protection by aspirin (ASA), despite
      regular antiplatelet prophylaxis at the standard dosing regimen, and (iv)
      stratification of patients deserving different antiplatelet strategies, based on
      the metabolic phenotype. Taken together, these pathophysiological aspects may
      contribute to the development of promising mechanism-based therapeutic strategies
      to reduce the progression of atherothrombosis in diabetic subjects. 

PMID- 25986600
TI  - Intakes of omega-3 polyunsaturated fatty acids and blood pressure change over
      time: Possible interaction with genes involved in 20-HETE and EETs metabolism.
AB  - BACKGROUND: A high intake of omega-3 polyunsaturated fatty acids (omega-3 PUFAs),
      has been associated with reduced levels of blood pressure (BP). Their
      antihypertensive action may be due to the reduction of the omega-6/omega-3 ratio
      and the resulting competitive effect of omega-3 as compared to arachidonic acid
      (an omega-6 PUFA) as a substrate of cytochrome P450 (CYP450) enzymes involved in
      the production of vasoactive mediators. Some functional polymorphisms (SNPs), in
      genes which encode for the same enzymes, were associated with hypertension and
      ischemic stroke in the Malmo Diet and Cancer (MDC), a Swedish urban-based
      longitudinal study. The aim of this study was to evaluate the effect of the
      intake of different types of PUFAs on BP change over time (Delta-BP; mean follow
      up 16.6+/-1.5 years; n=3.550 with complete phenotypic data), also considering the
      interaction with SNPs in genes involved in their metabolism via CYP450. METHODS:
      PUFA intakes were collected by a modified diet history method, and functional
      SNPs in CYP4F2, CYP4A11, CYP2J2 and EPHX2 were genotyped by Taqman. RESULT: We
      did not find any overall association between omega-6 and omega-3 PUFA intakes, or
      their ratio, with Delta-BP but observed an interaction between CYP4F2 V433M
      genotype and total omega-3, alpha-linolenic acid and linoleic/alpha-linolenic
      ratio, so that a higher omega-3 PUFA intake was significantly associated with a
      more pronounced BP decrease over time in subjects with the 433VV genotype (
      0.041+/-0.018 mmHg/year; p=0.024; p-interaction=0.031) CONCLUSIONS: Our data do
      not support a major role of omega-6 or omega-3 PUFA intakes on BP change over
      time, but suggest a possible interaction of omega-3 PUFA with the CYP4F2 V433M.

PMID- 25986599
TI  - Arachidonic acid monooxygenase: Genetic and biochemical approaches to
      physiological/pathophysiological relevance.
AB  - Studies with rat genetic models of hypertension pointed to roles for the CYP2C
      and CYP4A arachidonic acid epoxygenases and omega-hydroxylases in tubular
      transport, hemodynamics, and blood pressure control. Further progress in defining
      their physiological functions and significance to human hypertension requires
      conclusive identifications of the relevant genes and proteins. Here we discuss
      unequivocal evidence of roles for the murine Cyp4a14, Cyp4a10, and Cyp2c44 genes
      in the pathophysiology of hypertension by showing that: (a) Cyp4a14(-/-) mice
      develop sexually dimorphic hypertension associated with renal vasoconstriction,
      and up-regulated expression of Cyp4a12a and pro-hypertensive 20
      hydroxyeicosatetraenoic acid (20-HETE) levels, and b) Cyp4a10(-/-) and Cyp2c44(-/
      ) mice develop salt sensitive hypertension linked to downregulation or lack of
      the Cyp2c44 epoxygenase, reductions in anti-hypertensive epoxyeicosatrienoic
      acids (EETs), and increases in distal sodium reabsorption. Based on these
      studies, the human CYP4A11 and CYPs 2C8 and 2C9 genes and their products are
      identified as potential candidates for studies of the molecular basis of human
      hypertension. 

PMID- 25986601
TI  - When will 'open science' become simply 'science'?
AB  - Open science describes the practice of carrying out scientific research in a
      completely transparent manner, and making the results of that research available
      to everyone. Isn't that just 'science'? 

PMID- 25986602
TI  - Upregulation of T-type Ca2+ channels in long-term diabetes determines increased
      excitability of a specific type of capsaicin-insensitive DRG neurons.
AB  - BACKGROUND: Previous studies have shown that increased excitability of capsaicin
      sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2-4
      weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type
      Ca(2+) current. In longer-term diabetes (after the 8th week) thermal hyperalgesia
      is changed to hypoalgesia that is accompanied by downregulation of T-type current
      in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of
      diabetic neuropathy other than thermal persist in STZ-diabetic animals and
      patients during progression of diabetes into later stages suggesting that other
      types of DRG neurons may be sensitized and contribute to pain. In this study, we
      examined functional expression of T-type Ca(2+) channels in capsaicin-insensitive
      DRG neurons and excitability of these neurons in longer-term diabetic rats and in
      thermally hypoalgesic diabetic rats. RESULTS: Here we have demonstrated that in
      STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH
      sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and
      thermally hypoalgesic diabetic rats. This upregulation was not accompanied by
      significant changes in biophysical properties of T-type channels suggesting that
      a density of functionally active channels was increased. Sensitivity of T-type
      current to amiloride (1 mM) and low concentration of Ni(2+) (50 MUM) implicates
      prevalence of Cav3.2 subtype of T-type channels in the capsaicin-insensitive low
      pH-sensitive neurons of both naive and diabetic rats. The upregulation of T-type
      channels resulted in the increased neuronal excitability of these nociceptive
      neurons revealed by a lower threshold for action potential initiation, prominent
      afterdepolarizing potentials and burst firing. Sodium current was not
      significantly changed in these neurons during long-term diabetes and could not
      contribute to the diabetes-induced increase of neuronal excitability.
      CONCLUSIONS: Capsaicin-insensitive low-pH-sensitive type of DRG neurons shows
      diabetes-induced upregulation of Cav3.2 subtype of T-type channels. This
      upregulation results in the increased excitability of these neurons and may
      contribute to nonthermal nociception at a later-stage diabetes.

PMID- 25986603
TI  - Building bridges between doctors and patients: the design and pilot evaluation of
      a training session in argumentation for chronic pain experts.
AB  - BACKGROUND: Shared decision-making requires doctors to be competent in exchanging
      views with patients to identify the appropriate course of action. In this paper
      we focus on the potential of a course in argumentation as a promising way to
      empower doctors in presenting their viewpoints and addressing those of patients.
      Argumentation is the communication process in which the speaker, through the use
      of reasons, aims to convince the interlocutor of the acceptability of a
      viewpoint. The value of argumentation skills for doctors has been addressed in
      the literature. Yet, there is no research on what a course on argumentation might
      look like. In this paper, we present the content and format of a training session
      in argumentation for doctors and discuss some insights gained from a pilot study
      that examined doctors' perceived strengths and limitations vis-a-vis this
      training. METHODS: The training session (eight hours) combined different aspects
      from prominent theories of argumentation and was designed to strengthen doctors'
      argumentative discussion skills. A convenient, self-selected sample of 17 doctors
      who were experts in the field of chronic pain participated in the training and
      evaluated it via a feedback form and semi-structured interviews. RESULTS: The
      participants found that the training session gave a structure to types of
      communication they use to interact with their patients, and taught them
      techniques that can increase their effectiveness. Moreover, it provided tools to
      help address some of the challenges of modern doctor-patient interactions,
      including dealing with patients' unrealistic expectations and medically
      inaccurate beliefs, and reaching agreement when there are differences of opinion.
      CONCLUSIONS: This study enriches the research in the field of medical education.
      In line with the findings of studies that explore the value of argumentation in
      different fields, argumentative discussion skills can be applied by doctors to
      express their views and to account for the views of patients without patronizing
      the interaction. In this paper, we provide a basis to reflect on the value of
      argumentation in enhancing patients' right to autonomy and self-determination in
      interactions with their doctors.

PMID- 25986604
TI  - Self-reports versus parental perceptions of health-related quality of life among
      deaf children and adolescents.
AB  - The aim of this study was to assess the agreement between deaf children's and
      adolescents' self-ratings of health-related quality of life (HRQoL) and their
      parents' proxy reports. This observational cross-sectional study included 114
      deaf 8- to 18-years-old students and proxy family members. HRQoL was measured
      using the KIDSCREEN-27 questionnaire, which was adapted to Spanish sign language
      for children, with a written version for parents. Respondents completed a self
      administered paper questionnaire. Parents' and children's mean scores differences
      were not significant, except for the "Autonomy and Parents" and "Peers and Social
      Support" dimensions. Children aged 8-11 years scored higher in some domains of
      QoL compared to those aged 12-18 years. The level of agreement between
      children/adolescents' and parents/proxies' responses was acceptable, except for
      the dimension "Autonomy and Parents." Overall, deaf children/adolescents' self
      ratings of HRQoL did not differ from their parents' proxy reports; however,
      differences were found in the dimensions that explored the quality of the
      interaction of children/adolescents and parents, the perceived level of autonomy,
      and social relations and support. 

PMID- 25986605
TI  - Endoplasmic reticulum stress-independent activation of unfolded protein response
      kinases by a small molecule ATP-mimic.
AB  - Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress
      sensors in the unfolded protein response. IRE1 also has an endoribonuclease
      activity, which initiates a non-conventional mRNA splicing reaction, while PERK
      phosphorylates eIF2alpha. We engineered a potent small molecule, IPA, that binds
      to IRE1's ATP-binding pocket and predisposes the kinase domain to
      oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically,
      activates it at low concentrations, resulting in a bell-shaped activation
      profile. We reconstituted IPA-activation of PERK-mediated eIF2alpha
      phosphorylation from purified components. We estimate that under conditions of
      maximal activation less than 15% of PERK molecules in the reaction are occupied
      by IPA. We propose that IPA binding biases the PERK kinase towards its active
      conformation, which trans-activates apo-PERK molecules. The mechanism by which
      partial occupancy with an inhibitor can activate kinases may be wide-spread and
      carries major implications for design and therapeutic application of kinase
      inhibitors. 

PMID- 25986606
TI  - Pharmacological Induction of Human Fetal Globin Gene in Hydroxyurea-Resistant
      Primary Adult Erythroid Cells.
AB  - Pharmacological induction of the fetal gamma globin gene and the consequent
      formation of HbF (alpha2/gamma2) in adult erythroid cells are one feasible
      therapeutic strategy for sickle cell disease (SCD) and severe beta-thalassemias.
      Hydroxyurea (HU) is the current drug of choice for SCD, but serious side effects
      limit its clinical use. Moreover, 30 to 50% of patients are irresponsive to HU
      treatment. We have used high-throughput screening to identify
      benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one and its derivatives (compounds
      I to VI) as potent gamma globin inducers. Of the compounds, I to V exert superior
      gamma globin induction and have better therapeutic potential than HU, likely
      because of their activation of the p38 mitogen-activated protein kinase (MAPK)
      signaling pathway and modulation of expression levels and/or chromosome binding
      of gamma globin gene regulators, including BCL11A, and chromatin structure over
      the gamma globin promoter. Unlike sodium butyrate (NaB), the global levels of
      acetylated histones H3 and H4 are not changed by compound II treatment.
      Remarkably, compound II induces the gamma globin gene in HU-resistant primary
      human adult erythroid cells, the p38 signaling pathway of which appears to be
      irresponsive to HU and NaB as well as compound II. This study provides a new
      framework for the development of new and superior compounds for treating SCD and
      severe beta-thalassemias.

PMID- 25986607
TI  - Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in
      Association with Crx in the Postnatal Mouse Retina.
AB  - The Rax homeobox gene plays essential roles in multiple processes of vertebrate
      retina development. Many vertebrate species possess Rax and Rax2 genes, and
      different functions have been suggested. In contrast, mice contain a single Rax
      gene, and its functional roles in late retinal development are still unclear. To
      clarify mouse Rax function in postnatal photoreceptor development and
      maintenance, we generated conditional knockout mice in which Rax in maturing or
      mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO
      mice). When Rax was inactivated in postnatal Rax iCKO mice, developing
      photoreceptor cells showed a significant decrease in the level of the expression
      of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a
      specific decrease in cone cell numbers. In luciferase assays, we found that Rax
      and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that
      an optimum Rax expression level to transactivate photoreceptor gene expression
      exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and
      their coimmunoprecipitation was observed in cultured cells. Taken together, these
      results suggest that Rax plays essential roles in the maturation of both cones
      and rods and in the survival of cones by regulating photoreceptor gene expression
      with Crx in the postnatal mouse retina. 

PMID- 25986608
TI  - Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational
      Coactivator of Transforming Growth Factor beta Early Protransforming Events in
      Breast Epithelial Cells.
AB  - Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in
      breast cancers in association with disease progression and reduced survival. Much
      remains to be understood regarding the role of eIF4E in human cancer. We
      determined, using immortalized human breast epithelial cells, that elevated
      expression of eIF4E translationally activates the transforming growth factor beta
      (TGF-beta) pathway, promoting cell invasion, a loss of cell polarity, increased
      cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is
      shown to facilitate the selective translation of integrin beta1 mRNA, which
      drives the translationally controlled assembly of a TGF-beta receptor signaling
      complex containing alpha3beta1 integrins, beta-catenin, TGF-beta receptor I, E
      cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes
      nonmalignant breast epithelial cells to activation by typically substimulatory
      levels of activated TGF-beta. TGF-beta can promote cellular differentiation or
      invasion and transformation. As a translational coactivator of TGF-beta, eIF4E
      confers selective mRNA translation, reprogramming nonmalignant cells to an
      invasive phenotype by reducing the set point for stimulation by activated TGF
      beta. Overexpression of eIF4E may be a proinvasive facilitator of TGF-beta
      activity. 

PMID- 25986609
TI  - Male-Specific Cardiac Dysfunction in CTP:Phosphoethanolamine Cytidylyltransferase
      (Pcyt2)-Deficient Mice.
AB  - Phosphatidylethanolamine (PE) is the most abundant inner membrane phospholipid.
      PE synthesis from ethanolamine and diacylglycerol is regulated primarily by
      CTP:phosphoethanolamine cytidylyltransferase (Pcyt2). Pcyt2(+/-) mice have
      reduced PE synthesis and, as a consequence, perturbed glucose and fatty acid
      metabolism, which gradually leads to the development of hyperlipidemia, obesity,
      and insulin resistance. Glucose and fatty acid uptake and the corresponding
      transporters Glut4 and Cd36 are similarly impaired in male and female Pcyt2(+/-)
      hearts. These mice also have similarly reduced phosphatidylinositol 3-kinase
      (PI3K)/Akt1 signaling and increased reactive oxygen species (ROS) production in
      the heart. However, only Pcyt2(+/-) males develop hypertension and cardiac
      hypertrophy. Pcyt2(+/-) males have upregulated heart AceI expression, heart
      phospholipids enriched in arachidonic acid and other n-6 polyunsaturated fatty
      acids, and dramatically increased ROS production in the aorta. In contrast,
      Pcyt2(+/-) females have unmodified heart phospholipids but have reduced heart
      triglyceride levels and altered expression of the structural genes Acta (low) and
      Myh7 (high). These changes together protect Pcyt2(+/-) females from cardiac
      dysfunction under conditions of reduced glucose and fatty acid uptake and heart
      insulin resistance. Our data identify Pcyt2 and membrane PE biogenesis as
      important determinants of gender-specific differences in cardiac lipids and heart
      function. 

PMID- 25986611
TI  - Sex influenced association of directly measured insulin sensitivity and serum
      transaminase levels: Why alanine aminotransferase only predicts cardiovascular
      risk in men?
AB  - BACKGROUND: Non alcoholic fatty liver disease (NAFLD) is an independent
      cardiovascular (CV) risk factor which is closely associated with insulin
      resistance measured by both direct or indirect methods. Gender specific findings
      in the relationship between alanine aminotransferase (ALT) and CV disease, the
      prevalence of NAFLD and type 2 diabetes (T2DM) have been published recently. The
      aim of the present study was to explore the gender aspects of the association
      between insulin sensitivity, liver markers and other metabolic biomarkers in
      order to elucidate the background behind the sex influenced difference in both
      NAFLD, T2DM and their association with CV risk. PATIENTS AND METHODS: 158 female
      (47 normal and 111 impaired glucose intolerant) and 148 male (74 normal and 74
      impaired glucose tolerant) subjects were included (mean age: 46.5 +/- 8.31 vs.
      41.6 +/- 11.3, average Hba1c < 6.1 %, i.e. prediabetic population, drug naive at
      the time of the study). Subjects underwent a hyperinsulinemic normoglycemic clamp
      to determine muscle glucose uptake (M3), besides liver function tests and other
      fasting metabolic and anthropometric parameters were determined. RESULTS:
      Significant bivariate correlations were found between clamp measured M3 and all
      three liver enzymes (ALT, aspartate aminotransferase and gamma-glutamyl
      transferase) in both sexes. When data were adjusted for possible metabolic
      confounding factors correlations ceased in the male population but stayed
      significant in the female group. Feature selection analysis showed that ALT is an
      important attribute for M3 in the female but not in male group (mean Z: 3.85 vs.
      0.107). Multiple regression analysis confirmed that BMI (p < 0.0001) and ALT (p =
      0.00991) significantly and independently predicted clamp measured muscle glucose
      uptake in women (R(2) = 0.5259), while in men serum fasting insulin (p = 0.0210)
      and leptin levels (p = 0.0294) but none of the liver enzymes were confirmed as
      significant independent predictors of M3 (R(2) = 0.4989). CONCLUSION: There is a
      gender specific association between insulin sensitivity, metabolic risk factors
      and liver transaminase levels. This might explain the sex difference in the
      predictive role of ALT elevation for CV disease. Moreover, ALT may be used as a
      simple diagnostic tool to identify insulin resistant subjects only in the female
      population according to our results.

PMID- 25986610
TI  - Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for
      Mitosis.
AB  - Scaffold attachment factor A (SAF-A), also called heterogenous nuclear
      ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA
      dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK
      catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts
      with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA
      PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on
      serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1)
      rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells,
      and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in
      mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to
      alanine have multiple characteristics of aberrant mitoses, including misaligned
      chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through
      mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1
      and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of
      SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and
      timely exit from mitosis. 

PMID- 25986613
TI  - Colonic transit in children and adolescents with chronic constipation.
AB  - OBJECTIVE: The aim of this study was to assess clinical features and colonic
      transit patterns in Brazilian children with refractory constipation. METHODS:
      From 2010 to 2013, 79 constipated patients received follow-up care in a tertiary
      hospital. Of these patients, 28 (aged 8-14 years) were refractory to conventional
      therapy and underwent a simplified visual method of nuclear colonic transit
      study, by ingestion of a liquid meal containing 9.25 MBq/kg of (99m)Tc-phytate.
      Abdominal static images were taken immediately and at two, six, 24, 30, and 48h
      after ingestion for qualitative analysis of the radio marker progression through
      the colon. RESULTS: Two patterns of colonic transit were found: slow colonic
      transit (SCT, n=14), when images at 48h showed a larger part of the tracer
      remained in proximal and transverse colon, and distal retention (DR, n=14), when
      after 30h, the radio isotope passed the transverse colon and was retained in the
      rectosigmoid up to 48h. The SCT and DR group included, respectively, nine and ten
      males; median ages in the nuclear study of 11 and 10 years, p=0.207; median
      duration of constipation of seven and six years, p=0.599. Constipation appearing
      during first year age (p=0.04) and report of soft stools (p=0.02) were more
      common in SCT patients. Palpable abdominal fecal impaction was found only in DR
      group. Appendicostomy for antegrade continence enema was successful in 4/12 (30%)
      of SCT patients (median follow-up: 2.4 years). CONCLUSION: Nuclear transit study
      distinguished two colonic dysmotility patterns and was useful for guiding
      refractory patients to specific therapies.

PMID- 25986612
TI  - HIV testing in the maternity ward and the start of breastfeeding: a survival
      analysis.
AB  - OBJECTIVE: The purpose of this study was to analyze the factors that influence of
      the time between birth and the beginning of breastfeeding, especially at the
      moment of the rapid HIV test results at hospital admission for delivery. METHODS:
      Cohort study of 932 pregnant women who underwent rapid HIV test admitted in the
      hospital for delivery in Baby-Friendly Hospitals. The survival curves of time
      from birth to the first feeding were estimated by the Kaplan-Meier method and the
      joint effect of independent variables by the Cox model with a hierarchical
      analysis. As the survival curves were not homogeneous among the five hospitals,
      hindering the principle of proportionality of risks, the data were divided into
      two groups according to the median time of onset of breastfeeding at birth in
      women undergoing rapid HIV testing. RESULTS: Hospitals with median time to
      breastfeeding onset at birth of up to 60 min were considered as early
      breastfeeding onset and those with higher medians were considered as late
      breastfeeding onset at birth. Risk factors common to hospitals considered to be
      with early and late breastfeeding onset at birth were: cesarean section (RR=1.75
      [95% CI: 1.38-2.22]; RR=3.83 [95% CI: 3.03-4.85]) and rapid test result after
      birth (RR=1.45 [95% CI: 1.12-1.89]; RR=1.65 [95% CI: 1.35-2.02]), respectively;
      and hospitals with late onset: starting prenatal care in the third trimester
      (RR=1.86 [95% CI: 1.16-2.97]). CONCLUSIONS: The onset of breastfeeding is
      postponed, even in Baby-Friendly Hospitals, when the results of the rapid HIV
      test requested in the maternity are not available at the time of delivery.

PMID- 25986614
TI  - Prevalence of asthenopia in children: a systematic review with meta-analysis.
AB  - OBJECTIVE: To estimate the prevalence of asthenopia in 0-18 year-old children
      through a systematic review and meta-analysis of prevalence studies. SOURCES:
      Inclusion criteria were population-based studies from 1960 to May of 2014
      reporting the prevalence of asthenopia in children. The search was performed
      independently by two reviewers in the PubMed, EMBASE, and LILACS databases, with
      no language restriction. This systematic review was performed in accordance with
      the Cochrane Collaboration guidelines and the PRISMA Statement. Downs and Black
      score was used for quality assessment. SUMMARY OF FINDINGS: Out of 1692
      potentially relevant citations retrieved from electronic databases and searches
      of reference lists, 26 were identified as potentially eligible. Five of these
      studies met the inclusion criteria, comprising a total of 2465 subjects. Pooled
      prevalence of asthenopia was 19.7% (12.4-26.4%). The majority of children with
      asthenopia did not present visual acuity or refraction abnormalities. The largest
      study evaluated 1448 children aged 6 years and estimated a prevalence of 12.6%.
      Associated risk factors were not clearly established. CONCLUSION: Although
      asthenopia is a frequent and relevant clinical problem in childhood, with
      potential consequences for learning, the scarcity of studies about the prevalence
      and clinical impact of asthenopia hinders the effective planning of public health
      measures.

PMID- 25986616
TI  - Synthesis and Characterization of the LiMnBO3-LiCoBO3 Solid Solution and Its Use
      as a Lithium-Ion Cathode Material.
AB  - A complete solid solution of m-Li(Mn1-xCox)BO3 has been successfully synthesized
      for the first time with the idea of improving the average potential versus m
      LiMnBO3. These compounds have been obtained by a multiple-step process.
      Interestingly, transmission electron microscopy results indicate that the C2/c
      space group previously reported for m-LiMBO3 (M = Mn, Co) cannot describe m
      Li(Mn1-xCox)BO3 compounds. Each material shows electrochemical activity, without
      in situ carbon coating. Despite a large polarization, we report a capacity of
      almost 60 mAh/g at the first discharge at C/20 rate with good stability up to
      five cycles for LiMn0.7Co0.3BO3. 

PMID- 25986617
TI  - Stem Cell and Idiopathic Pulmonary Fibrosis: Mechanisms and Treatment.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease
      resulting from multiplex causes. Evidence indicates that stem/progenitor cells
      might play a key role in IPF pathogenesis and repair, which may provide some
      novel potential strategies for the future treatment of IPF. In this review, we
      first summarize the current understanding of the relationship between stem cells
      and IPF and then review the advancements made in recent clinical trials using
      stem/progenitor cells, especially mesenchymal stem cells, in treating IPF and
      their interpretations. 

PMID- 25986615
TI  - Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric
      outpatient setting.
AB  - OBJECTIVE: Two randomized controlled clinical trials have shown that
      Lactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children
      hospitalized due to acute infectious diarrhea. This was the first trial
      evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute
      infectious diarrhea. METHODS: This was a multicenter, randomized, single-blinded,
      case control clinical trial in children with acute watery diarrhea. A total of 64
      children who presented at outpatient clinics were enrolled. The probiotic group
      received 1*10(8)CFU L. reuteri DSM 17938 for five days in addition to oral
      rehydration solution (ORS) and the second group was treated with ORS only. The
      primary endpoint was the duration of diarrhea (in hours). The secondary endpoint
      was the number of children with diarrhea at each day of the five days of
      intervention. Adverse events were also recorded. RESULTS: The mean duration of
      diarrhea was significantly reduced in the L. reuteri group compared to the
      control group (approximately 15h, 60.4+/-24.5h [95% CI: 51.0-69.7h] vs. 74.3+/
      15.3h [95% CI: 68.7-79.9h], p<0.05). The percentage of children with diarrhea was
      lower in the L. reuteri group (13/29; 44.8%) after 48h than the control group
      (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79, p<0.01). From the 72nd hour of
      intervention onwards, there was no difference between the two groups in the
      percentage of children with diarrhea. No adverse effects related to L. reuteri
      were noted. CONCLUSION: L. reuteri DSM 17938 is effective, safe, and well
      tolerated in outpatient children with acute infectious diarrhea.

PMID- 25986618
TI  - Therapeutic Angiogenesis in Ischemic Tissues by Growth Factors and Bone Marrow
      Mononuclear Cells Administration: Biological Foundation and Clinical Prospects.
AB  - The processes of new vessels formation in tissues are supported by two definite
      mechanisms: de novo development of blood vessels (vasculogenesis) through the
      accumulation of progenitor cells during early prenatal stage, and extension of a
      pre-existing microcirculatory network by endothelial cell germination
      (angiogenesis), the essential mechanism of blood vessel formation in postnatal
      period. Angiogenesis is associated with a series of inductive, permissive and
      restrictive communications that result in the appearance, differentiation, and
      formation of new vessels. The goal of therapeutic angiogenesis is to improve
      blood circulation, relay survival factors and regenerative stem cell populations
      to sites of tissue repair, and ultimately recover function and form of the
      tissue. Growth factors and bone marrow mononuclear cells represent a very
      interesting research field for the realization of therapeutic angiogenesis in
      ischemic tissues. They provide a potential key component in the healing processes
      of ischemic injured tissues. 

PMID- 25986619
TI  - The Challenge of a "Functional Cure" for AIDS by Gene Modified HSCT Therapy.
AB  - Acquired immunodeficiency syndrome (AIDS), an infectious disease which is
      difficult to be cured, is regularly and effectively treated with anti-retroviral
      therapy in clinic. When considering about the defects of antiretroviral therapy
      (ART), patients need a new way to cure AIDS. With the development of genetic
      engineering technology and humanized mouse models, a new way has been found to
      achieve a "functional cure" for AIDS. One/some specific gene(s), such as CCR5 and
      CXCR4, can be knocked out to produce HIV-resisting cells, so as to achieve the
      purpose of curing AIDS. To find a safe and effective therapy for AIDS, treatment
      strategy and technical scheme should be improved and optimized in many aspects.
      Moreover, different stages of works have been done in laboratory and in clinic
      based on this gene mutation strategy. However, a great deal of challenge has
      emerged while great progress has been made. Safety considerations and
      effectiveness of gene modified stem cell in clinic are major obstacles of the
      application of this strategy. 

PMID- 25986620
TI  - Stem cells contributing to postnatal skeletogenesis in the mouse bone marrow.
AB  - Postnatal skeletogenesis is a highly regulated process that subpopulations of
      bone marrow stem cells differentiate into mature skeletal tissues to maintain and
      repair the postnatal skeletons. Based on their skeletogenic capacity, purified
      bone marrow stem cells have been used to repair and replace damaged skeletal
      tissues in recent years. In the meantime, significant effort has been devoted to
      unveil the nature and function of the "skeletogenic" precursors in vivo. In this
      review, we summarized our current understanding of the identification and fate
      mapping of the stem cells contributing to postnatal skeletogenesis in the mouse
      bone marrow. 

PMID- 25986621
TI  - PPARgamma and Wnt Signaling in Adipogenic and Osteogenic Differentiation of
      Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) arise from a variety of tissues, including bone
      marrow and adipose tissue and, accordingly, have the potential to differentiate
      into multiple cell types, including osteoblasts and adipocytes. Research on MSCs
      to date has demonstrated that a large number of transcription factors and
      ectocytic or intrastitial signaling pathways regulate adipogenic and osteogenic
      differentiation. A theoretical inverse relationship exists in adipogenic and
      osteogenic lineage commitment and differentiation, such that signaling pathways
      induce adipogenesis at the expense of osteogenesis and vice versa. For example,
      peroxisome proliferator-activated receptor gamma(PPARgamma), which belongs to the
      nuclear hormone receptor superfamily of ligand-activated transcription factors,
      is known to function as a master transcriptional regulator of adipocyte
      differentiation, and inhibit osteoblast differentiation. Moreover, recent studies
      have demonstrated that inducers of osteogenic differentiation, such as bone
      morphogenetic protein (BMP) and Wnt, inhibit the function of PPARgamma
      transactivation during MSC differentiation towards adipocytes through a variety
      of mechanisms. To illustrate this, the canonical Wnt/beta-catenin pathway
      represses expression of PPARgamma mRNA, whereas the noncanonical Wnt pathway
      activates histone methyltransferases that inhibit PPARgamma transactivation via
      histone H3 lysine 9 (H3K9) methylation of its target genes. The role of microRNAs
      (miRNAs) in adipogenesis and osteoblastogenesis is garnering increased attention,
      and studies in this area have shed light on the integration of miRNAs with Wnt
      signaling and transcription factors such as Runx2 and PPARgamma. This review
      summarizes our current understanding of the mechanistic basis of these signaling
      pathways, and indicates future clinical applications for stem cell-based cell
      transplantation and regenerative therapy. 

PMID- 25986622
TI  - Challenge of Mesenchymal Stem Cells Against Diabetic Foot Ulcer.
AB  - Mesenchymal stem cells (MSCs) play an important role in embryonic development and
      tissue regeneration in adult life owing to their high competency and self-renewal
      features. MSCs represent an important stem cell population with multipotent
      capabilities that may have high utility for translational clinical applications.
      MSCs can differentiate into a variety of cell types, especially fascia originated
      cells, and provide soluble factors for regeneration of tissues and organs. In in
      vitro environments, stem cells are capable of reproducing while preserving their
      properties; therefore, assuming stem cells could be reproduced in sufficient
      quantity, they would be appropriate for genetic operations. Stem cells can be
      used in tissue engineering, preventing rejection of bone marrow/ stem cell grafts
      by supporting hematopoiesis and recovery of autoimmune diseases, and cell therapy
      through their immunosuppressive properties. Mesenchymal stem cells have the
      potential capability to renew deformed organs and assist in tissue repair. In the
      field of wound healing, use of BM-MSCs is effective through modulating
      inflammation, extracellular matrix production, migration of keratinocytes, and
      angiogenesis for cell therapies. A significant complication of diabetes is
      diabetic foot ulcers, which affect quality of life and threaten life. In this
      article, we review recent studies with favorable results related to MSCs, which
      have become an important area of study in terms of tissue regeneration and
      regenerative medicine with diabetic foot ulcers. 

PMID- 25986623
TI  - Pluripotency Crossroads: Junction of Transcription Factors, Epigenetic
      Mechanisms, MicroRNAs, and Long Non-coding RNAs.
AB  - Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) and have the
      potency to differentiate into three germ layers (ectoderm, endoderm, and
      mesoderm). This potency of ESCs, called pluripotency, is critical for maintaining
      stemness. Transcriptional regulatory circuitry preserving stemness consists of
      transcription factors (TFs), epigenetic mechanisms, microRNAs (miRNAs or miRs),
      and long non-coding RNAs (lncRNAs). In this circuitry, components assist each
      other to activate essential genes for maintaining pluripotency and suppressing
      lineage-specific genes. TFs act directly by binding to their binding sites in the
      genome or indirectly by activating another gene (such as a miR), epigenetic
      mechanisms play their role by providing an activatory or inhibitory context for
      transcription, miRNAs regulate gene expression at the post-transcriptional level,
      and lncRNAs act as a scaffold function for epigenetic elements, regulating gene
      expression in ESCs. All these factors create a crossroad and collaborate to
      sustain stemness in the ESCs. Herein, we explain the role of each member in this
      circuitry and demonstrate the significance of the crossroad for keeping stemness.

PMID- 25986624
TI  - Prognostic Factors for Survival After Recurrence in Patients With Completely
      Resected Lung Adenocarcinoma: Important Roles of Epidermal Growth Factor Receptor
      Mutation Status and the Current Staging System.
AB  - Epidermal growth factor receptor (EGFR) status and pathological stage (p-stage)
      were shown to be essential prognostic factors for estimating survival after
      recurrence of lung adenocarcinoma. In patients with EGFR mutations, those with
      early p-stage tumors showed better survival after disease recurrence than those
      with advanced p-stage tumors. The EGFR mutation status and p-stage could also
      prompt the design of clinical trials on adjuvant therapy for patients after
      complete surgical resection. BACKGROUND: The current staging system and epidermal
      growth factor receptor (EGFR) mutation status are key factors for predicting
      survival. However, the significance of these factors as predictors of survival
      after disease recurrence (PRS) has not been sufficiently elucidated. The
      objective of this study was to investigate the clinicopathological factors,
      particularly the EGFR mutation status and pathological stage (p-stage), which
      affect PRS in patients with completely resected lung adenocarcinoma. PATIENTS AND
      METHODS: We retrospectively reviewed the data of 198 consecutive lung
      adenocarcinoma patients with disease recurrence who previously underwent complete
      surgical resection in our hospital. RESULTS: Of the 198 patients, 117 were
      examined for EGFR mutations (mutants). Mutants were detected in 57 patients
      (28.7%). The patients with mutants had a significantly better 3-year PRS (3y-PRS)
      rate (68.6%) than those with an EGFR wild type (WT) status (51.7%) or an unknown
      (UN) status (27.0%). The 3y-PRS rates for p-stage I to II (p-I-II) and p-stage
      III (p-III) were 52.5% and 29.3%, respectively. Multivariate survival analysis
      showed that the EGFR mutation status and p-stage had significant associations
      with favorable PRS. The 3y-PRS rate for mutants/p-I-II (81.4%) was significantly
      better than that for mutants/p-III (48.0%). Conversely, there was no significant
      difference between mutants/p-III and WT/UN/p-I-II (3y-PRS: 40.7%) or between
      mutants/p-III and WT/UN/p-III (3y-PRS: 24.4%). CONCLUSION: EGFR status and p
      stage were shown to be essential prognostic factors for estimating PRS. In
      patients with mutants, those with early p-stage tumors showed better PRS than
      those with advanced p-stage tumors.

PMID- 25986625
TI  - Axillary vein thrombosis induced by an increasingly popular oscillating dumbbell
      exercise device: a case report.
AB  - A 53 year-old male presented with a one-day history of a swollen arm and dull,
      aching pain in the right upper extremity. The patient reported commencing
      exercising daily over the prior week with a modified, oscillating dumbbell;
      commonly referred to as a Shake Weight. Imaging revealed an occlusive thrombus in
      the right axillary, proximal brachial and basilic veins. The patient was treated
      with a 24-hour tPA infusion followed by mechanical thrombectomy, balloon
      angioplasty, and stent placement for a residual thrombus and stenosis. The
      patient was discharged the following day on warfarin and aspirin. This is the
      first report of effort-induced thrombosis of the upper extremity following the
      use of a modified, oscillating dumbbell. Due to the growing popularity of
      modified dumbbells and the possible risk for axillary vein thrombosis,
      consideration should be made to caution consumers of this potential complication.

PMID- 25986626
TI  - Mitochondrial Pharmaceutics: A New Therapeutic Strategy to Ameliorate Oxidative
      Stress in Alzheimer's Disease.
AB  - Association between amyloid-beta (Abeta) toxicity, mitochondrial dysfunction,
      oxidative stress and neuronal damage has been demonstrated in the pathophysiology
      of Alzheimer's disease (AD). In the early stages of the disease, the defect in
      energy metabolism was found to be severe. This may probably due to the Abeta and
      ROS-induced declined activity of complexes in electron transport chain (ETC) as
      well as damages to mitochondrial DNA. Though clinically inconclusive,
      supplementation with antioxidants is reported to be beneficial especially in the
      early stages of the disease. A mild to moderate improvement in dementia is
      possible with therapy using antioxidants viz coenzyme Q10 (ubiquinone), alpha 
      lipoic acid, selenium, omega-3 fatty acids and vitamin E, emphasize their
      possible role as an adjuvant with the existing conventional treatment. Since
      mitochondrial dysfunction has been observed, a new therapeutic strategy called as
      'Mitochondrial Medicine' which is aimed to maintain the energy production as well
      as to ameliorate the enhanced apoptosis of nerve cells, has been developed.
      Mitochondrial CoQ10, Szeto-Schiller peptide-31 and superoxide dismutase/ catalase
      mimetic, EUK-207 were the mitochondrial targeted agents demonstrated in
      experimental studies. This article discusses the mitochondrial impairment and the
      possible mitochondria targeted therapeutic intervention in AD. 

PMID- 25986627
TI  - Development and Validation of a Rapid (13)C6-Glucose Isotope Dilution UPLC-MRM
      Mass Spectrometry Method for Use in Determining System Accuracy and Performance
      of Blood Glucose Monitoring Devices.
AB  - BACKGROUND: There is currently considerable discussion about the accuracy of
      blood glucose concentrations determined by personal blood glucose monitoring
      systems (BGMS). To date, the FDA has allowed new BGMS to demonstrate accuracy in
      reference to other glucose measurement systems that use the same or similar
      enzymatic-based methods to determine glucose concentration. These types of
      reference measurement procedures are only comparative in nature and are subject
      to the same potential sources of error in measurement and system perturbations as
      the device under evaluation. It would be ideal to have a completely orthogonal
      primary method that could serve as a true standard reference measurement
      procedure for establishing the accuracy of new BGMS. METHODS: An isotope-dilution
      liquid chromatography/mass spectrometry (ID-UPLC-MRM) assay was developed using
      (13)C6-glucose as a stable isotope analogue to specifically measure glucose
      concentration in human plasma, and validated for use against NIST standard
      reference materials, and against fresh isolates of whole blood and plasma into
      which exogenous glucose had been spiked. Assay performance was quantified to NIST
      traceable dry weight measures for both glucose and (13)C6-glucose. RESULTS: The
      newly developed assay method was shown to be rapid, highly specific, sensitive,
      accurate, and precise for measuring plasma glucose levels. The assay displayed
      sufficient dynamic range and linearity to measure across the range of both normal
      and diabetic blood glucose levels. Assay performance was measured to within the
      same uncertainty levels (<1%) as the NIST definitive method for glucose
      measurement in human serum. CONCLUSIONS: The newly developed ID UPLC-MRM assay
      can serve as a validated reference measurement procedure to which new BGMS can be
      assessed for glucose measurement performance.

PMID- 25986628
TI  - Use of a Combined Blood-Glucose- and beta-Ketone-Measuring Device Improves
      Glycemic Control in Insulin-Treated Patients With Diabetes: The Gold Plus Study.
AB  - BACKGROUND: Using self-measurements of blood glucose (SMBG) is daily routine for
      patients with insulin-treated diabetes, however measuring beta-ketones in blood
      is not widespread. How the use of a combined device, which can measure both, is
      accepted in daily routine by patients and will lead to better glycemic control is
      not well studied. METHODS: This multicenter, prospective, noninterventional study
      assessed the impact of routine use of the GlucoMen(r) LX Plus on patient
      acceptance, usage and glycemic control among insulin-treated patients with
      diabetes mellitus type 1 and type 2. A1c and self-reported frequency of SMBG were
      evaluated at baseline and also postprandial SMBG, beta-ketone measurements, and
      use of reminders after 3 and 6 months of use. A total of 631 patients, 254 type
      1/350 type 2 (27 no type specified), with mean (SD) baseline A1c 8.5% (1.5), age
      54.6 (15.6) years, and 47.3% female were studied. RESULTS: Frequent use of SMBG
      at baseline led to a higher decrease in A1c at 6 month (V3): -0.3% if SMBG
      measured up to 1/day versus -0.9% in 4-6/day. Increase of SMBG frequency during
      the study showed also a negative correlation to A1c, 9.2% at V1 versus 7.6% at
      V3. Postprandial SMBG was done by 77.7% and beta-ketone measurements by 45.5% of
      all patients; the reminders were used by 33.4% and led to an increased frequency
      of SMBG at 6 months. CONCLUSIONS: A combined device for SMBG and beta-ketone
      measurements is well accepted by patients with insulin-treated diabetes and can
      lead through the avoidance or detection of ketoacidosis/increased frequency of
      SMBG and increased awareness of the patients to an improved glycemic outcome.

PMID- 25986629
TI  - Predictors of Hypoglycemia in the ASPIRE In-Home Study and Effects of Automatic
      Suspension of Insulin Delivery.
AB  - BACKGROUND: Hypoglycemia varies between patients with type 1 diabetes and is the
      main obstacle to therapy intensification. We investigated known and potential
      risk factors for hypoglycemia in subjects with type 1 diabetes. METHOD: In the
      ASPIRE In-Home study (NCT01497938), a randomized trial of the threshold suspend
      (TS) feature of sensor-augmented insulin pump (SAP) therapy, subjects' propensity
      to nocturnal hypoglycemia (NH) was established in a 2-week run-in phase and
      assessed in a 3-month study phase via continuous glucose monitoring. Categorical
      variables were tested for association with NH rates in both phases. RESULTS:
      Elevated rates of NH were significantly associated with baseline A1C <=7%, with
      bolus insulin deliveries unassisted by the bolus estimation calculator, and with
      assignment to the control group during the study phase. CONCLUSIONS: Routine use
      of the TS feature and the bolus estimation calculator are strategies that may
      reduce the risk of NH.

PMID- 25986630
TI  - Seeking Health Information Online: Association with Young Australian Women's
      Physical, Mental, and Reproductive Health.
AB  - BACKGROUND: Relatively little is known about the extent to which young adults use
      the Internet as a health information resource and whether there are factors that
      distinguish between those who do and do not go online for health information.
      OBJECTIVE: The aim was to identify the sociodemographic, physical, mental, and
      reproductive health factors associated with young women's use of the Internet for
      health information. METHODS: We used data from 17,069 young women aged 18-23
      years who participated in the Australian Longitudinal Study on Women's Health.
      Multivariable logistic regression was used to estimate the association between
      sociodemographic, physical, mental, and reproductive health factors associated
      with searching the Internet for health information. RESULTS: Overall, 43.54%
      (7433/17,069) of women used the Internet for health information. Women who used
      the Internet had higher odds of regular urinary or bowel symptoms (OR 1.44, 95%
      CI 1.36-1.54), psychological distress (very high distress: OR 1.24, 95% CI 1.13
      1.37), self-reported mental health diagnoses (OR 1.16, 95% CI 1.09-1.23), and
      menstrual symptoms (OR 1.25, 95% CI 1.15-1.36) than women who did not use the
      Internet for health information. Internet users were less likely to have had
      blood pressure checks (OR 0.85, 95% CI 0.78-0.93) and skin cancer checks (OR
      0.90, 95% CI 0.84-0.97) and to have had a live birth (OR 0.74, 95% CI 0.64-0.86)
      or pregnancy loss (OR 0.88, 95% CI 0.79-0.98) than non-Internet users.
      CONCLUSIONS: Women experiencing "stigmatized" conditions or symptoms were more
      likely to search the Internet for health information. The Internet may be an
      acceptable resource that offers "anonymized" information or support to young
      women and this has important implications for health service providers and public
      health policy.

PMID- 25986632
TI  - B-cell-independent lymphoid tissue infection by a B-cell-tropic rhadinovirus.
AB  - Lymphocytes provide gammaherpesviruses with a self-renewing substrate for
      persistent infection and with transport to mucosal sites for host exit. Their
      role in the initial colonization of new hosts is less clear. Murid herpesvirus 4
      (MuHV-4), an experimentally accessible, B-cell-tropic rhadinovirus (gamma-2
      herpesvirus), persistently infects both immunocompetent and B-cell-deficient
      mice. A lack of B-cells did not compromise MuHV-4 entry into lymphoid tissue,
      which involved myeloid cell infection. However, it impaired infection
      amplification and MuHV-4 exit from lymphoid tissue, which involved myeloid to B
      cell transfer. 

PMID- 25986631
TI  - The Classification and Evolution of Enzyme Function.
AB  - Enzymes are the proteins responsible for the catalysis of life. Enzymes sharing a
      common ancestor as defined by sequence and structure similarity are grouped into
      families and superfamilies. The molecular function of enzymes is defined as their
      ability to catalyze biochemical reactions; it is manually classified by the
      Enzyme Commission and robust approaches to quantitatively compare catalytic
      reactions are just beginning to appear. Here, we present an overview of studies
      at the interface of the evolution and function of enzymes. 

PMID- 25986633
TI  - Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1
      infection from the cornea to neurons of trigeminal ganglia.
AB  - Herpes simplex virus 1 (human herpesvirus 1) initially infects epithelial cells
      of the mucosa and then goes on to infect sensory neurons leading ultimately to a
      latent infection in trigeminal ganglia (TG). UL24 is a core herpesvirus gene that
      has been identified as a determinant of pathogenesis in several
      Alphaherpesvirinae, although the underlying mechanisms are unknown. In a mouse
      model of ocular infection, a UL24-deficient virus exhibited a reduction in viral
      titres in tear films of 1 log10, whilst titres in TG are often below the level of
      detection. Moreover, the efficiency of reactivation from latency was also
      severely reduced. Herein, we investigated how UL24 contributed to acute infection
      of TG. Our results comparing the impact of UL24 on viral titres in eye tissue
      versus in tear films did not reveal a general defect in virus release from the
      cornea. We also found that the impairment of replication seen in mouse primary
      embryonic neurons with a UL24-deficient virus was not more severe than that
      observed in an epithelial cell line. Rather, in situ histological analyses
      revealed that infection with a UL24-deficient virus led to a significant
      reduction in the number of acutely infected neurons at 3 days post-infection
      (p.i.). Moreover, there was a significant reduction in the number of neurons
      positive for viral DNA at 2 days p.i. for the UL24-deficient virus as compared
      with that observed for WT or a rescue virus. Our results supported a model
      whereby UL24 functions in the dissemination of acute infection from the cornea to
      neurons in TG. 

PMID- 25986635
TI  - Analytical performance, agreement and user-friendliness of six point-of-care
      testing urine analysers for urinary tract infection in general practice.
AB  - OBJECTIVE: Various point-of-care testing (POCT) urine analysers are commercially
      available for routine urine analysis in general practice. The present study
      compares analytical performance, agreement and user-friendliness of six different
      POCT urine analysers for diagnosing urinary tract infection in general practice.
      SETTING: All testing procedures were performed at a diagnostic centre for primary
      care in the Netherlands. Urine samples were collected at four general practices.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Analytical performance and agreement of
      the POCT analysers regarding nitrite, leucocytes and erythrocytes, with the
      laboratory reference standard, was the primary outcome measure, and analysed by
      calculating sensitivity, specificity, positive and negative predictive value, and
      Cohen's kappa coefficient for agreement. Secondary outcome measures were the user
      friendliness of the POCT analysers, in addition to other characteristics of the
      analysers. RESULTS: The following six POCT analysers were evaluated: Uryxxon
      Relax (Macherey Nagel), Urisys 1100 (Roche), Clinitek Status (Siemens), Aution 11
      (Menarini), Aution Micro (Menarini) and Urilyzer (Analyticon). Analytical
      performance was good for all analysers. Compared with laboratory reference
      standards, overall agreement was good, but differed per parameter and per
      analyser. Concerning the nitrite test, the most important test for clinical
      practice, all but one showed perfect agreement with the laboratory standard. For
      leucocytes and erythrocytes specificity was high, but sensitivity was
      considerably lower. Agreement for leucocytes varied between good to very good,
      and for the erythrocyte test between fair and good. First-time users indicated
      that the analysers were easy to use. They expected higher productivity and
      accuracy when using these analysers in daily practice. CONCLUSIONS: The overall
      performance and user-friendliness of all six commercially available POCT urine
      analysers was sufficient to justify routine use in suspected urinary tract
      infections in general practice.

PMID- 25986634
TI  - Replication and transmission of mammalian-adapted H9 subtype influenza virus in
      pigs and quail.
AB  - Influenza A virus is a major pathogen of birds, swine and humans. Strains can
      jump between species in a process often requiring mutations and reassortment,
      resulting in outbreaks and, potentially, pandemics. H9N2 avian influenza is
      predominant in poultry across Asia and occasionally infects humans and swine.
      Pandemic H1N1 (H1N1pdm) is endemic in humans and swine and has a history of
      reassortment in pigs. Previous studies have shown the compatibility of H9N2 and
      H1N1pdm for reassortment in ferrets, a model for human infection and
      transmission. Here, the effects of ferret adaptation of H9 surface gene segments
      on the infectivity and transmission in at-risk natural hosts, specifically swine
      and quail, were analysed. Reassortant H9N1 and H9N2 viruses, carrying seven or
      six gene segments from H1N1pdm, showed infectivity and transmissibility in swine,
      unlike the wholly avian H9N2 virus with ferret-adapted surface genes. In quail,
      only the reassortant H9N2 with the six internal gene segments from the H1N1pdm
      strain was able to infect and transmit, although less efficiently than the wholly
      avian H9N2 virus with ferret-adapted surface genes. These results highlight that
      ferret-adapted mutations on the haemagglutinin of H9 subtype virus do not
      restrict the ability of the virus to infect swine and quail, and that the ability
      to transmit in these species depends on the context of the whole virus. As such,
      this study emphasizes the threat that H9N2 reassortant viruses pose to humans and
      agricultural species and the importance of the genetic constellation of the virus
      to its ability to replicate and transmit in natural hosts of influenza. 

PMID- 25986637
TI  - Variability in potentially preventable hospitalisations: an observational study
      of clinical practice patterns of general practitioners and care outcomes in the
      Basque Country (Spain).
AB  - OBJECTIVES: To explain the variability in the frequency of potentially
      preventable hospitalisations (ambulatory care sensitive conditions, ACSCs) based
      on factors at multiple levels (individual, health professional, health centre and
      health district), and specifically using resource efficiency indicators for
      general practitioners (GPs). DESIGN: Cross-sectional study. We analysed primary
      care electronic health records and hospital discharge data using multilevel mixed
      models. SETTING: Primary care network of the Basque Health Service (Spain).
      PARTICIPANTS: All the residents in the Basque Country >=14 years of age, covered
      by the public healthcare system (n=1,959,682), and all the GPs (n=1193) and
      health centres (n=130). MAIN OUTCOME MEASURES: Individuals admitted for ACSCs,
      over a 12- month period. RESULTS: Admissions for ACSCs were less frequent among
      patients who were female, middle-aged or from the highest socioeconomic classes.
      The health centre variables considered and GP list size were not found to be
      significant. After adjusting for the variables studied including morbidity, the
      risk of hospital admission was higher among individuals under the care of GPs
      with greater than expected numbers of patient visits and prescribing costs
      (OR=1.27 (95% CI 1.18 to 1.37); 1.16 (1.08 to 1.25)), and who make fewer
      referrals than the mean among their colleagues (OR=1.33 (1.22 to 1.44)).
      CONCLUSIONS: When assessing activities and procedure indicators in primary care,
      we should also define outcome-based criteria. Specifically, GPs who are
      repeatedly visited by their patients, have higher prescribing costs and are more
      reluctant to refer patients to specialists obtain poorer outcomes.

PMID- 25986638
TI  - Mindfulness-based stress reduction (MBSR) as sole intervention for non
      somatisation chronic non-cancer pain (CNCP): protocol for a systematic review and
      meta-analysis of randomised controlled trials.
AB  - INTRODUCTION: Chronic non-cancer pain (CNCP) affects up to 50% of the world's
      population. It impacts negatively on quality of life; entailing high costs on our
      medical systems, and translates to economic burden due to work loss. Aetiology of
      CNCP is complex and multifactorial, embracing the somatosensory, cognitive and
      affective domains. Opioid analgesia and other invasive interventions are often
      inadequate for clinical management of CNCP. Recently, mindfulness-based stress
      reduction (MBSR) has become a popular therapy for various medical conditions,
      including CNCP. However, studies reported varying efficacies, and relevant
      systematic reviews have included clinical trials with inherent heterogeneity
      either in study conditions or types of interventions used. Our study aims to
      provide an updated and more critical evaluation of the efficacy of MBSR as the
      intervention for non-somatisation CNCP. METHODS AND ANALYSIS: A systematic review
      with meta-analysis of randomised controlled trials published in English will be
      performed in accordance with the Preferred Reporting Items for Systematic reviews
      and Meta-analyses (PRISMA) guidelines and the Cochrane Collaboration format.
      MEDLINE, EMBASE, PsychINFO, and the Cochrane Central Register of Controlled
      Trials Intervention, will be searched independently by reviewers using defined
      MeSH terms. Studies with full texts using MBSR as the main intervention on
      patients with non-somatising CNCP will be included. Outcome measures include pain
      scores and disability assessment scales. Continuous data will be meta-analysed
      using the RevMan 5 Review Manager programme. Primary analysis will adopt the
      random effects model in view of heterogeneity between trials. The standardised
      mean difference will be expressed as the effect size with 95% CIs. Forest plots,
      funnel plots, the I(2) statistic and the Cochrane Risks of Bias Assessment table
      will be included. ETHICS AND DISSEMINATION: No ethics approval is deemed
      necessary. Results of this study will be disseminated via peer-reviewed
      publications and scientific meetings. TRIALS REGISTRATION NUMBER: PROSPERO
      CRD42014015568.

PMID- 25986636
TI  - Acupuncture for functional constipation: protocol of an individual patient data
      meta-analysis.
AB  - INTRODUCTION: Functional constipation (FC) is a common gastrointestinal disease.
      Systematic reviews indicate that acupuncture may be effective for patients with
      FC. However, this conclusion is not convincing due to the quality, sample size
      and methodological heterogeneity of the studies included by these systematic
      reviews. Therefore, it is necessary for us to conduct a meta-analysis of
      individual patient data (IPD) from high-quality clinical trials to determine
      whether acupuncture is effective for patients with FC. METHODS AND ANALYSIS:
      Randomised controlled trials (RCTs) of acupuncture for adult patients with FC
      will be searched in several databases from inception to April 2015. The
      corresponding authors of eligible studies will be contacted and invited to
      contribute raw data. The primary outcome is the change in spontaneous defaecation
      per week from baseline. The secondary outcomes include the proportion of
      responders, changes in stool quality, mean transit time, proportion of patients
      using laxatives and adverse events. We will check all of the data and perform
      reanalysis according to the statistical methodology reported in previous
      publications. Then we will harmonise the raw data and use a two-step method to
      conduct the IPD meta-analysis. First, we will calculate the effect size of
      acupuncture of each trial by analysis of covariance, with the principal end point
      as the dependent variable and the baseline scores as the covariates. Second, the
      effect size of acupuncture in each original study will be combined in the meta
      analysis. DISSEMINATION: On the basis of the IPD meta-analysis of high-quality
      RCTs, this review will answer the question of whether acupuncture is effective
      for FC. The findings of the review will be disseminated through peer-review
      publications and conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO
      2014 CRD42014009901.

PMID- 25986639
TI  - Understanding patient experiences of self-managing chronic dizziness: a
      qualitative study of booklet-based vestibular rehabilitation, with or without
      remote support.
AB  - OBJECTIVE: This study explores participants' experience of self-management of
      dizziness using booklet-based vestibular rehabilitation (VR), with or without
      expert telephone support. DESIGN: Semistructured qualitative interviews were
      conducted. SETTING: Participants were recruited from primary care practices as
      part of a large RCT. PARTICIPANTS: Interviews were carried out with 33 people (10
      men and 23 women; age 27-84) self-managing chronic dizziness using booklet-based
      vestibular rehabilitation, with or without expert telephone support. RESULTS:
      Data were analysed using inductive thematic analysis. The majority of
      participants in both groups reported a positive experience of VR therapy, with
      many participants reporting an improvement in their dizziness symptoms since
      undertaking the therapy. Participants in the telephone support group felt that a
      genuine relationship developed between them and their therapist within three
      short sessions, and described their therapy sessions as reassuring, encouraging
      and motivational. CONCLUSIONS: The VR treatment booklet appears to be a valued
      tool for self-managing chronic dizziness and people appreciate receiving remote
      telephone support. TRIAL REGISTRATION NUMBER: NCT00732797.

PMID- 25986640
TI  - What factors contribute to positive early childhood health and development in
      Australian Aboriginal children? Protocol for a population-based cohort study
      using linked administrative data (The Seeding Success Study).
AB  - INTRODUCTION: Australian Aboriginal children are more likely than non-Aboriginal
      children to have developmental vulnerability at school entry that tracks through
      to poorer literacy and numeracy outcomes and multiple social and health
      disadvantages in later life. Empirical evidence identifying the key drivers of
      positive early childhood development in Aboriginal children, and supportive
      features of local communities and early childhood service provision, are lacking.
      METHODS AND ANALYSIS: The study population will be identified via linkage of
      Australian Early Development Census data to perinatal and birth registration data
      sets. It will include an almost complete population of children who started their
      first year of full-time school in New South Wales (NSW), Australia, in 2009 and
      2012. Early childhood health and development trajectories for these children will
      be constructed via linkage to a range of administrative data sets relating to
      birth outcomes, congenital conditions, hospital admissions, emergency department
      presentations, receipt of ambulatory mental healthcare services, use of general
      practitioner services, contact with child protection and out-of-home care
      services, receipt of income assistance and fact of death. Using multilevel
      modelling techniques, we will quantify the contributions of individual-level and
      area-level factors to variation in early childhood development outcomes in
      Aboriginal and non-Aboriginal children. Additionally, we will evaluate the impact
      of two government programmes that aim to address early childhood disadvantage,
      the NSW Aboriginal Maternal and Infant Health Service and the Brighter Futures
      Program. These evaluations will use propensity score matching methods and
      multilevel modelling. ETHICS AND DISSEMINATION: Ethical approval has been
      obtained for this study. Dissemination mechanisms include engagement of
      stakeholders (including representatives from Aboriginal community controlled
      organisations, policy agencies, service providers) through a reference group, and
      writing of summary reports for policy and community audiences in parallel with
      scientific papers.

PMID- 25986641
TI  - Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of
      an intervention to reduce time-to-consult with symptoms of lung cancer.
AB  - INTRODUCTION: Lung cancer is the most common cancer worldwide, with 1.3 million
      new cases diagnosed every year. It has one of the lowest survival outcomes of any
      cancer because over two-thirds of patients are diagnosed when curative treatment
      is not possible. International research has focused on screening and community
      interventions to promote earlier presentation to a healthcare provider to improve
      early lung cancer detection. This paper describes the protocol for a phase II,
      multisite, randomised controlled trial, for patients at increased risk of lung
      cancer in the primary care setting, to facilitate early presentation with
      symptoms of lung cancer. METHODS/ANALYSIS: The intervention is based on a
      previous Scottish CHEST Trial that comprised of a primary-care nurse consultation
      to discuss and implement a self-help manual, followed by self-monitoring
      reminders to improve symptom appraisal and encourage help-seeking in patients at
      increased risk of lung cancer. We aim to recruit 550 patients from two Australian
      states: Western Australia and Victoria. Patients will be randomised to the
      Intervention (a health consultation involving a self-help manual, monthly prompts
      and spirometry) or Control (spirometry followed by usual care). Eligible
      participants are long-term smokers with at least 20 pack years, aged 55 and over,
      including ex-smokers if their cessation date was less than 15 years ago. The
      primary outcome is consultation rate for respiratory symptoms. ETHICS AND
      DISSEMINATION: Ethical approval has been obtained from The University of Western
      Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of
      Melbourne Human Research Committee (1 441 433). A summary of the results will be
      disseminated to participants and we plan to publish the main trial outcomes in a
      single paper. Further publications are anticipated after further data analysis.
      Findings will be presented at national and international conferences from late
      2016. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry
      ACTRN 1261300039 3752.

PMID- 25986642
TI  - Lower socioeconomic status, adiposity and negative health behaviours in youth: a
      cross-sectional observational study.
AB  - OBJECTIVE: Understanding obesity and its modifiable risk factors in youth is key
      to addressing the burden of cardiovascular disease later in life. Our aim was to
      examine the associations among adiposity, negative health behaviours and
      socioeconomic status in youth from the Niagara Region. DESIGN, SETTING AND
      PARTICIPANTS: Cross-sectional observational study of 3467 grade 9 students during
      their mandatory health and physical education class to investigate the
      association between socioeconomic status (postal code), self-reported health
      behaviour and adiposity in the Niagara Region, Ontario, Canada. RESULTS: Median
      household income was $63,696 and overall percentage below the after-tax low
      income cut-off was 4.2%. Negative health behaviours (especially skipped meals,
      lower fruit and vegetable consumption, higher screen time) were associated with
      lower income neighbourhoods, however, the absolute effect was small. Those
      participants in the lowest income quintile had a significantly greater body mass
      index z-score than those in the highest (0.72+/-1.19 vs 0.53+/-1.12), but the
      overall trend across quintiles was not statistically significant. A similar trend
      was noted for waist-to-height ratio. The lowest income neighbourhoods according
      to after-tax low-income cut-off had small but statistically significant
      associations with higher adiposity compared with the middle or highest income
      neighbourhoods. CONCLUSIONS: Obesity prevention efforts should target modifiable
      behaviours, with particular attention to adolescents from lower income families
      and neighbourhoods.

PMID- 25986644
TI  - COMMENTARY. Pre-emptive Nutrition: Refining the Targets of Drugs Targeted to
      Colorectal Cancer.
AB  - It is suggested that our current understanding of the role of nutrients in
      maintaining genomic stability might be strategically employed alongside current
      chemotherapy, in order to prevent the emergence of drug resistant tumors and
      optimize medicinal chemistry approaches. 

PMID- 25986645
TI  - Clonidine as an adjuvant in the management of acute poisoning by
      anticholinesterase pesticides.
AB  - INTRODUCTION: Anticholinesterase pesticides are widely used in agriculture and
      domestic settings throughout the world, and they are responsible for great
      morbidity and mortality. In Egypt and other developing countries, there is a
      pressing need for new affordable antidotes to treat anticholinesterase pesticide
      poisoning. Hence, this study was conducted to evaluate the safety and
      effectiveness of moderate doses of clonidine in the management of adult patients
      with acute anticholinesterase pesticide poisoning. METHODOLOGY: This study was an
      open-label, phase II pilot clinical trial. Sixty patients with acute
      anticholinesterase pesticide poisoning gave consent to participate in the study.
      They were divided into 2 equal groups, with 30 patients in each group. Group I
      received clonidine plus the routine treatment, while group II received only the
      routine treatment. Patients were subjected to full history taking, and their
      vital and clinical data were recorded. Serum cholinesterase levels and routine
      laboratory investigations were measured. The different outcomes of the patients
      were assessed. RESULTS: The baseline characteristics of both groups were similar.
      Thirteen (43.3%) patients developed significant hypotension during clonidine
      treatment. The clinical outcomes (including mortality, need for assisted
      ventilation, length of hospital stay, and total doses of atropine) showed no
      significant differences between the two groups. CONCLUSION: The use of clonidine
      in acute anticholinesterase pesticide poisoning may be associated with a high
      incidence of hypotension requiring intervention. The clinical outcomes may not
      significantly improve in clonidine-treated patients.

PMID- 25986643
TI  - Efficacy of temporary work modifications on disability related to musculoskeletal
      pain or depressive symptoms--study protocol for a controlled trial.
AB  - INTRODUCTION: Previous research suggests that work with a suitable workload may
      promote health and work retention in people with disability. This study will
      examine whether temporary work modifications at the early stage of work
      disability are effective in enhancing return to work (RTW) or staying at work
      among workers with musculoskeletal or depressive symptoms. METHODS AND ANALYSIS:
      A single-centre controlled trial with modified stepped wedge design will be
      carried out in eight enterprises and their occupational health services (OHSs) in
      nine cities in Finland. Patients seeking medical advice due to musculoskeletal
      pain (>=4 on a scale from 0-10) or depressive symptoms (>=1 positive response to
      2 screening questions) and fulfilling other inclusion criteria are eligible. The
      study involves an educational intervention among occupational physicians to
      enhance the initiation of work modifications. Primary outcomes are sustained RTW
      (>=4 weeks at work without a new sickness absence (SA)) and the total number of
      SA days during a 12-month follow-up. Secondary outcomes are intensity of
      musculoskeletal pain (scale 0-10), pain interference with work or sleep (scale 0
      10) and severity of depressive symptoms (Patient Health Questionnaire, PHQ-9),
      inquired via online questionnaires at baseline and 3, 6, 9 and 12 months after
      recruitment. Information on SA days will be collected from the medical records of
      the OHSs over 12 months, before and after recruitment. The findings will give new
      information about the possibilities of training physicians to initiate work
      modifications and their effects on RTW in employees with work disability due to
      musculoskeletal pain or depressive symptoms. ETHICS AND DISSEMINATION: The
      Coordinating Ethics Committee of Hospital District of Helsinki and Uusimaa has
      granted approval for this study. The results will be published in peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: ISRCTN74743666.

PMID- 25986646
TI  - Investigation into potential transmission sources of Giardia duodenalis in a
      threatened marsupial (Petrogale penicillata).
AB  - Assemblages of the protozoan parasite Giardia duodenalis common in humans and
      domestic species are increasingly identified in wildlife species, raising concern
      about the spill-over of pathogens from humans and domestic animals into wildlife.
      Here, the identity and prevalence of G. duodenalis in populations of a threatened
      marsupial, the brush-tailed rock-wallaby (Petrogale penicillata), was
      investigated. Identification of G. duodenalis isolates, across three loci (18S
      rRNA, beta-giardin and gdh), from rock-wallaby fecal samples (n = 318) identified
      an overall detection rate of 6.3%. No significant difference in G. duodenalis
      detection was found among captive, wild and supplemented populations. Isolates
      were assigned to the zoonotic assemblages A and B at 18S rRNA, with sub
      assemblages AI and BIV identified at the beta-giardin and gdh loci, respectively.
      Assemblages AI and BIV have previously been identified in human clinical cases,
      but also in domestic animals and wildlife. The identification of these
      assemblages in brush-tailed rock-wallabies suggests there are transmission routes
      of G. duodenalis from humans or other animals to Australian wildlife, both in
      captivity and in the wild.

PMID- 25986647
TI  - Buprenorphine Treatment and 12-step Meeting Attendance: Conflicts,
      Compatibilities, and Patient Outcomes.
AB  - This analysis examines patient experiences and outcomes with 12-step recovery
      group attendance during buprenorphine maintenance treatment (BMT), two approaches
      with traditionally divergent philosophies regarding opioid medications for
      treatment of opioid use disorder. Using quantitative (n = 300) and qualitative (n
      = 20) data collected during a randomized trial of counseling services in
      buprenorphine treatment, this mixed-methods analysis of African Americans in BMT
      finds the number of NA meetings attended in the prior 6 months was associated
      with a higher rate of retention in BMT (p < .001) and heroin/cocaine abstinence
      at 6 month follow-up (p = .005). However, patients whose counselors required them
      to attend 12-step meetings did not have better outcomes than patients not
      required to attend such meetings. Qualitative narratives highlighted patients'
      strategies for managing dissonant viewpoints on BMT and disclosing BMT status in
      community 12-step meetings. Twelve-step meeting attendance is associated with
      better outcomes for BMT patients over the first 6 months of treatment. However,
      there is no benefit to requiring meeting attendance as a condition of treatment,
      and clinicians should be aware of potential philosophical conflicts between 12
      step and BMT approaches.

PMID- 25986649
TI  - Acute Median Nerve Problems in the Setting of a Distal Radius Fracture.

PMID- 25986650
TI  - Biomechanical Analysis of Scapholunate Ligament Repair Techniques.
AB  - PURPOSE: To evaluate the biomechanical properties of 3 scapholunate repair
      techniques. METHODS: In 51 cadavers, the scapholunate ligament was exposed
      through a dorsal approach, incised at its scaphoid insertion, and repaired using
      1 of 3 techniques: 2 single-loaded suture anchors, 2 double-loaded suture
      anchors, or 2 transosseous sutures. Twenty-four repaired specimens underwent load
      to failure (LTF) testing using tensile distraction on a servo-hydraulic machine.
      Twenty-seven specimens underwent cyclical testing to measure gap formation at the
      scapholunate joint. RESULTS: The mode of failure was suture pullout through the
      substance of the ligament in 22 specimens, failure at the bone suture interface
      in 1, and anchor pullout in 1. Double-loaded anchor repairs demonstrated a
      significantly higher mean ultimate LTF compared with single-loaded anchor (91 N
      vs 35 N) and transosseous (91 N vs 60 N) repairs. Transosseous repairs
      demonstrated a higher mean ultimate LTF compared with single-loaded suture
      repairs (60 N vs 35 N). After 300 cycles, the average gap for the transosseous
      repair group was double that for the single- and double-loaded repairs, although
      not statistically significant. CONCLUSIONS: Primary scapholunate ligament repairs
      using double-loaded suture anchors demonstrated significantly higher strength
      compared with single-loaded anchors and transosseous repairs. On cyclic loading,
      transosseous repairs demonstrated the greatest gap formation with no measurable
      difference between single- and double-loaded repairs. CLINICAL RELEVANCE: In a
      cadaveric model for primary repairs, double-loaded suture anchors demonstrated
      the highest LTF and offer a similar but unproven performance in vivo.

PMID- 25986648
TI  - Efficacy and safety of Gantong Granules in the treatment of common cold with wind
      heat syndrome: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Although the common cold is generally mild and self-limiting, it is a
      leading cause of consultations with doctors and missed days from school and work.
      In light of its favorable effects of relieving symptoms and minimal side-effects,
      Traditional Chinese Medicine (TCM) has been widely used to treat the common cold.
      However, there is a lack of robust evidence to support the clinical utility of
      such a treatment. This study is designed to evaluate the efficacy and safety of
      Gantong Granules compared with placebo in patients with the common cold with wind
      heat syndrome (CCWHS). METHODS/DESIGN: This is a multicenter, phase IIb, double
      blind, placebo-controlled and randomized clinical trial. A total of 240 patients
      will be recruited, from 5 centers across China and randomly assigned to the high
      dose group, medium-dose group, low-dose group or placebo control group in a
      1:1:1:1 ratio. All subjects will receive the treatment for 3 to 5 days, followed
      by a 7-day follow-up period. The primary outcome is the duration of all symptoms.
      Secondary outcomes include the duration of primary symptoms and each symptom,
      time to fever relief and time to fever clearance, change in TCM symptom score,
      and change in Symptom and Sign Score. DISCUSSION: This trial will provide high
      quality evidence on the efficacy and safety of Gantong Granules in treating
      CCWHS, and help to optimize the dose selection for a phase III clinical trial.
      TRIAL REGISTRATION: The registration number is ChiCTR-TRC-14004255 , which was
      assigned by the Chinese Clinical Trial Registry on 12 February 2014.

PMID- 25986651
TI  - Trapeziometacarpal Arthritis: A Prospective Clinical Evaluation of the Thumb
      Adduction and Extension Provocative Tests.
AB  - PURPOSE: To determine the diagnostic performance (ie, sensitivity, specificity,
      interrater reliability) of the thumb metacarpal adduction and extension tests
      against traditional examination maneuvers for trapeziometacarpal (TMC) arthritis.
      METHODS: This cross-sectional study recruited 129 patients from 2 outpatient
      offices at a tertiary institution. All patients had radiographic wrist
      examinations and completed a standardized physical examination consisting of the
      thumb adduction and extension tests as well as standard examination maneuvers for
      radial wrist and thumb pain. The physical examinations were performed by 1 of 2
      attending physicians and an independent examiner. Patients were recruited for 3
      diagnostic groups: TMC arthritis, radial wrist or hand pain, and nonradial wrist
      pain controls. Statistical analysis calculated the sensitivity, specificity, and
      interrater reliability of each physical examination maneuver for detecting TMC
      arthritis. RESULTS: The thumb adduction maneuver was found to have a sensitivity
      of 0.94 (confidence interval [CI], 0.82-0.98) and a specificity of 0.93 (CI, 0.86
      0.97). The thumb extension maneuver had a sensitivity of 0.94 (CI, 0.82-0.98) and
      a specificity of 0.95 (CI, 0.87-0.98). The interrater reliability was excellent
      for both the adduction (kappa = 0.79) and the extension tests (kappa = 0.84). The
      grind test had a sensitivity of 0.44 (CI, 0.30-0.59), a specificity of 0.92 (CI,
      0.84-0.97), and poor interrater reliability (0.31). Point tenderness at the TMC
      joint had a sensitivity of 0.94 (CI, 0.82-0.98), a specificity of 0.81 (CI, 0.71
      0.88) and fair interrater reliability (kappa = 0.63). CONCLUSIONS: The adduction
      and extension tests each proved to be more sensitive than the grind test for the
      detection of TMC arthritis. Further, these provocative tests were more specific
      for basal joint arthrosis than was the elicitation of point tenderness at the
      joint. The metacarpal adduction and extension maneuvers demonstrated excellent
      utility as screening tests for the identification of TMC arthritis. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 25986652
TI  - Triceps Tendinopathy.

PMID- 25986653
TI  - Ecophysiological responses of three Mediterranean invasive seaweeds (Acrothamnion
      preissii, Lophocladia lallemandii and Caulerpa cylindracea) to experimental
      warming.
AB  - The Mediterranean Sea is a hotspot for invasive species and projected
      Mediterranean warming might affect their future spreading. We experimentally
      examined ecophysiological responses to the temperature range 23-31  degrees C in
      three invasive seaweeds commonly found in the Mediterranean: Acrothamnion
      preissii, Caulerpa cylindracea and Lophocladia lallemandii. The warming range
      tested encompassed current and projected (for the end of 21st Century) maximum
      temperatures for the Mediterranean Sea. Optimal ecophysiological temperatures for
      A. preissii, C. cylindracea and L. lallemandii were 25  degrees C, 27  degrees C
      and 29  degrees C, respectively. Warming below the optimal temperatures enhanced
      RGR of all studied invasive seaweeds. Although sensitive, seaweed photosynthetic
      yield was less temperature-dependent than growth. Our results demonstrate that
      temperature is a key environmental parameter in regulating the ecophysiological
      performance of these invasive seaweeds and that Mediterranean warming conditions
      may affect their invasion trajectory.

PMID- 25986654
TI  - Marine debris ingestion by albatrosses in the southwest Atlantic Ocean.
AB  - Plastics and other marine debris affect wildlife through entanglement and by
      ingestion. We assessed the ingestion of marine debris by seven albatross species
      in the southwest Atlantic by analyzing stomach contents of birds killed in
      fisheries. Of the 128 specimens examined, including four Diomedea species (n=78)
      and three Thalassarche species (n=50), 21 (16.4%) contained 1-4 debris items,
      mainly in the ventriculus. The most common type was plastic fragments. Debris was
      most frequent in Diomedea species (25.6%) and, particularly, Diomedea sanfordi
      (38.9%) and very rare in Thalassarche species (2.0%), presumably reflecting
      differences in foraging behavior or distribution. Frequency of occurrence was
      significantly higher in male than female Diomedea albatrosses (39.3% vs. 18.0%).
      Although levels of accumulated debris were relatively low overall, and unlikely
      to result in gut blockage, associated toxins might nevertheless represent a
      health risk for Diomedea albatrosses, compounding the negative impact of other
      human activities on these threatened species. 

PMID- 25986655
TI  - Organochlorine contaminants and maternal offloading in the lecithotrophic Pacific
      angel shark (Squatina californica) collected from southern California.
AB  - Pacific angel sharks (Squatina californica) are a benthic elasmobranch that
      occupy intermediate trophic level positions in coastal food webs. Angel sharks'
      life history characteristics make them susceptible to accumulating high amounts
      of contaminants. Four angel sharks were opportunistically captured in southern
      California and their liver and uterine contents were analyzed for PCBs, DDTs and
      other pesticides. High DDT:PCB ratios were found in the sharks indicating direct
      or indirect foraging near a local EPA Superfund Site. Organic contaminants were
      measured in ovulated eggs, indicating that females are able to maternally offload
      contaminants. Despite the potential mismatch between ovarian and uterine
      fecundity, we estimated females to offload approximately 13+/-5% of their total
      body load, which represents the upper limit of this capability. Although low in
      sample size, the initial findings from this study suggest that habitat use might
      play an important role in contaminant accumulation in this species. 

PMID- 25986656
TI  - New non-PBDE brominated flame retardants in sediment and plant samples from
      Jiaozhou Bay wetland.
AB  - Seven non-polybrominated diphenyl ethers (non-PBDE) (TBB, TBX, PBT, PBEB, HBB,
      DBHCTD and BB153) were analyzed in sediment and plant samples which were
      collected from Xiaojianxi landfill to Dagu river estuary in Jiaozhou Bay wetland.
      The species of non-PBDE were different in sediment and plant samples with the
      concentration of 0.41-9.66ngg(-1) and 0.15-1.2ngg(-1), respectively. DBHCTD was
      the main non-PBDE compared with other target compounds and its concentration was
      1.21-9.66ngg(-1)dw. Generally, the concentration of non-PBDE in sediment showed a
      decreasing tendency while discrete decline in plant has been revealed.
      Furthermore, DBHCTD, HBB, as well as other BFRs, might have a common BFRs
      degradation or similar accumulation potential in sediment, as their Pearson
      relationship p<0.05. Generally, the content of non-PBDE in Jiaozhou Bay wetland
      was higher than other published research. Therefore, more attention should be
      paid to non-PBDE on account of their persisting impact on human health and
      environment. 

PMID- 25986657
TI  - Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy
      homeostasis in mice.
AB  - Epidemiological evidence suggests that the consumption of a diet high in n-6
      polyunsaturated fatty acids (PUFA) is associated with the development of leptin
      resistance and obesity. We aim to examine the central effect of n-6 PUFA,
      arachidonic acid (ARA) on leptin sensitivity and leptin-regulated hepatic glucose
      and lipid metabolism. We found that intracerebroventricular injection of ARA (25
      nmol/day) for 2.5 days reversed the effect of central leptin on hypothalamic
      JAK2, pSTAT3, pAkt, and pFOXO1 protein levels, which was concomitant with a pro
      inflammatory response in the hypothalamus. ARA also attenuated the effect of
      central leptin on hepatic glucose and lipid metabolism by reversing the mRNA
      expression of the genes involved in gluconeogenesis (G6Pase, PEPCK), glucose
      transportation (GLUT2), lipogenesis (FAS, SCD1), and cholesterol synthesis (HMG
      CoA reductase). These results indicate that an increased exposure to central n-6
      PUFA induces central cellular leptin resistance with concomitant defective JAK2
      STAT3 and PI3K-Akt signaling.

PMID- 25986658
TI  - Fetuin A promotes lipotoxicity in beta cells through the TLR4 signaling pathway
      and the role of pioglitazone in anti-lipotoxicity.
AB  - OBJECTIVE: Fetuin A (FetA), a secreted glycoprotein, is known to affect
      inflammation and insulin resistance (IR) in obese humans and animals.
      Lipotoxicity from chronic hyperlipidemia damages pancreatic beta cells, hastening
      the onset of diabetes. We sought to determine whether FetA promotes lipotoxicity
      through modulation of the toll-like receptor 4 (TLR4) inflammatory signaling
      pathway as well as the protective effect of pioglitazone(PIO) on lipotoxicity.
      METHODS: betaTC6, a glucose-sensitive mouse pancreatic beta cell line, and
      Sprague-Dawley rats with diet-induced obesity, were used to investigate FetA
      mediated lipotoxicity. Protein expression/activation were measured by Western
      blotting. Small interfering (si)RNAs for TLR4 were used. Cell apoptosis was
      quantified by TUNEL analysis or flow cytometry, respectively. Insulin release was
      assessed with an insulin ELISA. RESULTS: FetA dose-dependently aggravated
      palmitic acid (PA)-induced betaTC6 cell apoptosis, insulin secretion impairment,
      and inhibition of the expression of G-protein-coupled receptor 40 (GPR40) and
      pancreatic duodenal homeobox-1(PDX-1). Combined FetA + PA induced TLR4
      expression, and subsequent inhibition of TLR4 signaling or expression was shown
      to prevent the strengthening effect of FetA on PA-induced lipotoxicity in betaTC6
      cells. FetA + PA induced p-JNK and nuclear factor-kappaB (NF-kappaB) subunit P65
      expression, and inhibition of this activity reduced PA+ FetA lipotoxicity in
      betaTC6 cells. PIO could ameliorate PA+ FetA-induced damage to betaTC6 cells.
      Similarly, PIO improved insulin secretion disorder, reduced apoptosis, decreased
      FetA, TLR4, p-JNK, NF-kappaB subunit P65 and cleaved caspase 3 expression, and
      increased GPR40 and PDX-1 expression in islet beta cells of diet-induced obese
      rats. The correlative bivariate analysis showed that increases in Fetuin A were
      directly proportional to the development of beta cell injury. CONCLUSIONS: FetA
      can promote lipotoxicity in beta cells through the TLR4-JNK-NF-kappaB signaling
      pathway. The protective effects of PIO on lipotoxicity in beta cells may involve
      the inhibition of the activation of the FetA and TLR4 signaling pathway.

PMID- 25986659
TI  - Preadipocyte proliferation is elevated by calcium sensing receptor activation.
AB  - Obesity is a major worldwide problem, despite considerable efforts against it.
      While excess body fat defines obesity, adipose tissue quality and functionality
      are key to whether cardiovascular and metabolic comorbidities develop. Adipose
      tissue cellular composition can vary considerably, and excess adipocyte
      progenitors (preadipocytes) is associated with obesity. We have proposed that
      calcium sensing receptor (CaSR) activation in adipose tissue leads to
      dysfunction. This study evaluated whether CaSR activation elevates preadipocyte
      proliferation. Human LS14 preadipocytes were exposed to CaSR activators
      cinacalcet (2 uM), GdCl3 (5 uM) and spermine (1 uM), and cell viability was
      evaluated after 72h. CaSR activators elevated proliferation by 19-24%, and CaSR
      silencing (siRNA) abolished the effect. Cinacalcet elevated phospho-ERK1/2
      content, and upstream inhibition of ERK1/2 phosphorylation reverted cinacalcet
      induced proliferation. Cinacalcet also elevated expression of the proinflammatory
      factors IL1beta, IL6 and CCL2. The results suggest that CaSR induces preadipocyte
      proliferation, partly through ERK1/2 activation. Considering reported
      proinflammatory and adipogenic CaSR effects, excess preadipocyte proliferation
      further supports the dysfunctional effect of CaSR in obesity.

PMID- 25986660
TI  - High Blood Pressure and Its Association With Incident Diabetes Over 10 Years in
      the Korean Genome and Epidemiology Study (KoGES).
AB  - OBJECTIVE: No prospective, community-based cohort studies have investigated the
      association between blood pressure and diabetes in Asian ethnicity. We
      investigated this issue in a 10-year prospective, community-based study of
      Koreans. RESEARCH DESIGN AND METHODS: We studied whether high blood pressure was
      associated with the development of diabetes in a population-based cohort, where
      we sampled ~5,000 random subjects each from rural and urban areas (age range 40
      69 years) during 2001-2010. Among 10,038 subjects, 8,359 without diabetes at
      baseline were categorized into normal (n = 4,809), prehypertension (n = 2,141),
      stage 1 hypertension (n = 804), and stage 2 hypertension (n = 605) groups,
      according to their blood pressure readings of <120/80 mmHg, 120-139/80-89 mmHg,
      140-159/90-99 mmHg, and >=160/100 mmHg, respectively. The development of diabetes
      was defined as a fasting glucose concentration of >=126 mg/dL or a postload
      glucose concentration of >=200 mg/dL, based on a 75-g oral glucose tolerance
      test, or the use of antidiabetic medication. RESULTS: During the 10-year follow
      up period, diabetes developed in 1,195 subjects (14.3%). The incidence of
      diabetes increased from 11.1% in the normal group to 17.0% in the prehypertension
      group, 17.7% in the stage 1 hypertension group, and 25.8% in the stage 2
      hypertension group (P < 0.001). After adjusting for anthropometric factors;
      family history of diabetes; biochemical parameters including C-reactive protein,
      A1C, and fasting glucose and postload 2-h glucose levels; and the use of lipid
      lowering medications, the hazard risks of diabetes development were 1.23 (95% CI
      1.06-1.42), 1.26 (1.04-1.54), and 1.60 (1.30-1.96), respectively, in the
      prehypertension, stage 1 hypertension, and stage 2 hypertension groups.
      CONCLUSIONS: Our findings indicate a grade association of baseline blood pressure
      with the development of diabetes in Korean individuals.

PMID- 25986662
TI  - [Usefulness of capsule endoscopy in obscure gastrointestinal bleeding].

PMID- 25986661
TI  - Early Detection and Treatment of Type 2 Diabetes Reduce Cardiovascular Morbidity
      and Mortality: A Simulation of the Results of the Anglo-Danish-Dutch Study of
      Intensive Treatment in People With Screen-Detected Diabetes in Primary Care
      (ADDITION-Europe).
AB  - OBJECTIVE: To estimate the benefits of screening and early treatment of type 2
      diabetes compared with no screening and late treatment using a simulation model
      with data from the ADDITION-Europe study. RESEARCH DESIGN AND METHODS: We used
      the Michigan Model, a validated computer simulation model, and data from the
      ADDITION-Europe study to estimate the absolute risk of cardiovascular outcomes
      and the relative risk reduction associated with screening and intensive
      treatment, screening and routine treatment, and no screening with a 3- or 6-year
      delay in the diagnosis and routine treatment of diabetes and cardiovascular risk
      factors. RESULTS: When the computer simulation model was programmed with the
      baseline demographic and clinical characteristics of the ADDITION-Europe
      population, it accurately predicted the empiric results of the trial. The
      simulated absolute risk reduction and relative risk reduction were substantially
      greater at 5 years with screening, early diagnosis, and routine treatment
      compared with scenarios in which there was a 3-year (3.3% absolute risk reduction
      [ARR], 29% relative risk reduction [RRR]) or a 6-year (4.9% ARR, 38% RRR) delay
      in diagnosis and routine treatment of diabetes and cardiovascular risk factors.
      CONCLUSIONS: Major benefits are likely to accrue from the early diagnosis and
      treatment of glycemia and cardiovascular risk factors in type 2 diabetes. The
      intensity of glucose, blood pressure, and cholesterol treatment after diagnosis
      is less important than the time of its initiation. Screening for type 2 diabetes
      to reduce the lead time between diabetes onset and clinical diagnosis and to
      allow for prompt multifactorial treatment is warranted.

PMID- 25986663
TI  - Retrieval of broken iliosacral screws: the power of a push screw.
AB  - Percutaneous iliosacral screw fixation is a common technique that is widely used
      for unstable posterior pelvic ring disruptions. Complications of posterior
      percutaneous iliosacral screw fixation include implant malpositioning and
      hardware failure. Removal of iliosacral screws in broken or symptomatic hardware
      is sometimes necessary. To our knowledge, there are few reports addressing pelvic
      implant removal, and most of those report on anterior pelvic implants and
      symphyseal plates. There are no reports describing techniques for retrieval of
      broken iliosacral screws. We present two cases involving removal of broken
      sacroiliac screws, review the literature regarding iliosacral implant extraction,
      and identify important aspects of safe extraction of iliosacral screws and the
      potential complications associated with their retrieval. We further describe a
      novel and powerful technique to facilitate percutaneous removal of broken screw
      fragments, using a "push screw" to drive a broken screw fragment from a position
      buried in bone.

PMID- 25986664
TI  - Proximal humerus fracture with injury to the axillary artery: a population-based
      study.
AB  - BACKGROUND: The available evidence regarding axillary artery injury as a result
      of proximal humerus fracture consists of individual case reports or small series.
      This study used nationally representative data to determine the prevalence and
      predictors of axillary artery injury secondary to proximal humerus fracture, and
      to characterise its influence on inpatient mortality, length of stay, cost and
      discharge disposition. METHODS: An estimated 388,676 inpatients with a proximal
      humerus fracture were identified in the Nationwide Inpatient Sample between 2002
      and 2011, 331 with concomitant axillary artery injury (8.5 per 10,000).
      Multivariable regression modelling was used to identify independent predictors of
      axillary artery injury and to assess its relationship with inpatient outcomes.
      RESULTS: Factors associated with axillary artery injury were male sex (odds ratio
      (OR): 1.6, 95% confidence interval (CI): 1.2-2.0), atherosclerosis (OR: 3.7, 95%
      CI: 2.5-5.4), open fracture (OR: 2.9, 95% CI: 1.9-4.5) and the presence of
      concomitant injuries, including brachial plexus injury (OR: 109, 95% CI: 79-151),
      shoulder dislocation (OR: 3.4, 95% CI: 2.0-5.8), scapula fracture (OR: 3.4, 95%
      CI: 2.1-5.4) and rib fracture (OR: 2.5, 95% CI: 1.6-4.0). Axillary artery injury
      was associated with increased length of stay, costs and mortality, but it did not
      affect discharge disposition. CONCLUSION: Our study provides important baseline
      information regarding the epidemiology of axillary artery injury secondary to
      proximal humerus fracture. Prompt identification of at-risk patients upon
      admission might lead to improved diagnosis and management of this vascular
      injury. LEVEL OF EVIDENCE: Prognostic level II.

PMID- 25986665
TI  - Ionising radiation exposure in patients with circular frame treatment of distal
      tibial fractures.
AB  - Total radiation exposure accumulated during circular frame treatment of distal
      tibial fractures was quantified in 47 patients treated by a single surgeon from
      February 2007 until Oct 2010. The radiation exposures for all relevant radiology
      procedures for the distal tibial injury were included to estimate the radiation
      risk to the patient. The median time of treatment in the frame was 169 days
      (range 105-368 days). Patients underwent a median of 13 sets of plain
      radiographs; at least one intra operative exposure and 16 patients underwent CT
      scanning. The median total effective dose per patient from time of injury to
      discharge was 0.025mSv (interquartile range 0.013-0.162 and minimum to maximum
      0.01-0.53). The only variable shown to be an independent predictor of cumulative
      radiation dose on multivariate analysis was the use of CT scanning. This was
      associated with a 13-fold increase in overall exposure. Radiation exposure during
      treatment of distal tibial fractures with a circular frame in this group was well
      within accepted safe limits. The fact that use of CT was the only significant
      predictor of overall exposure serves as a reminder to individually assess the
      risk and utility of radiological investigations on an individual basis. This is
      consistent with the UK legal requirements for justification of all X-ray imaging,
      as set out in the Ionising Radiation (Medical Exposure) Regulations 2000 [1]. 

PMID- 25986666
TI  - Epidemiology of falls among older adults: A cross sectional study from
      Chandigarh, India.
AB  - BACKGROUND: Fall is an important cause of injury morbidity in older adults.
      However, epidemiological information on fall is limited in low- and middle-income
      countries. We investigated the extent, pattern, characteristics, and context of
      falls in Chandigarh. METHODS: A cross sectional survey was carried out among 300
      persons (>=60 years), sampled from urban, rural and slums areas of Chandigarh,
      India from March 2011 to October 2012 using multistage cluster sampling. A pre
      tested interview schedule was used and relevant medical examinations were
      conducted. Multivariable logistic regression was carried out to estimate Odds
      Ratio (OR) and 95% confidence interval (CI). RESULTS: In the past one year, 31%
      (92/300) respondents reported one or more falls. On an average 0.67 fall episodes
      occurred/person/year (202/300). Most (68%; 63/92) falls occurred at home; 75%
      (47/63) occurred while carrying out activities such as toileting, bathing,
      sleeping and eating etc. Injuries due to falls were reported by 67% (62/92). In
      these cases, lower extremities, 37% (23/62) were the most common site of injury.
      Eight percent (5/62) reported fractures. A general physician was consulted by 44%
      (27/62), and 11% (7/62) utilized emergency services whilst another 11% (7/62) of
      fall injuries required hospital admission. Risk of fall was higher among females
      (OR 1.6, 95%CI 1.0-2.8, p 0.068), those taking four or more medicines (OR 2.1,
      95%CI 1.2-3.5, p 0.009) and having poor body balance (OR 1.9, 95%CI 1.0-3.4, p
      0.037). CONCLUSION: Fall injuries were common in older adults of Chandigarh.
      Large cohort studies are needed to identify risk factors particularly those
      related to home environment.

PMID- 25986667
TI  - White-eyed blowout fracture: Diagnostic pitfalls and review of literature.
AB  - White-eyed blowout fracture was first termed by Jordan et al. in individuals
      sustaining a blow to the periocular area and presenting with ocular symptoms,
      although with minimal soft tissue signs of trauma. It is often found in pure
      orbital floor blowout fractures among paediatric patients, and it could manifest
      as a linear or hinge-like trapdoor deformity. Unlike the more common open orbital
      blowout fractures with distinct diagnostic clinical signs, white-eyed blowout
      fractures are rarer and their diagnoses can be easily missed, subsequently
      costing an optimal time window for surgical intervention. This is critical as
      better outcomes are found with earlier release of entrapments. This report
      describes a case of a white-eyed blowout fracture in a 10-year-old child faced
      with its diagnostic challenges. The current literature review discusses the types
      of fracture pattern, signs and symptoms, mechanism of action, as well as timing
      of surgery. In view of the common complication of persistent diplopia, clinical
      pitfalls in achieving this diagnosis are emphasized to prevent any delay of
      treatment. Current literature evidences are weighted towards urgent surgical
      intervention, as positive outcomes are found to correlate with earlier release of
      entrapments. 

PMID- 25986668
TI  - The L5 transverse process fracture revisited. Does its presence predict the
      pelvis fracture instability?
AB  - BACKGROUND: The presence of a L5 transverse process fracture is reported in many
      texts to be a marker of pelvis fracture instability. There is paucity of
      literature to support this view. Only two previous studies have been performed on
      this subject with statistical analysis. METHODS: We conducted a retrospective
      cross-sectional review of all abdominopelvic CT scans performed for blunt
      abdominal trauma in a Level 1 Trauma Unit between January 2012 and August 2013. A
      total of 203 patients met our inclusion criteria. Fifty four (54) of these
      patients had an associated pelvis fracture. RESULTS: Of the 54 patients with
      pelvis fractures 26 (48%) had an unstable fracture (AO Type B and C) and 28 (52%)
      had a stable pelvis fracture (AO Type A). Five (19%) of the 26 patients with an
      unstable pelvis fracture had an associated L5 transverse process fracture. This
      association was not statistically significant (P=0.724). Seven (12%) of the 28
      patients with a stable fracture pattern had an associated L5 transverse process
      fracture. Three patients (2%) had an L5 transverse fracture in the absence of a
      demonstrable pelvis fracture. The relative risk of an unstable pelvis fracture in
      the presence of a L5 transverse process fracture is 1.2 (CI 0.6 2.3).
      CONCLUSIONS: The presence of an L5 transverse process fracture on an
      abdominopelvic CT scan is strongly associated with an underlying pelvis fracture
      (P<0.001). Statistically, its presence however does not strongly predict
      instability (P=0.724). The latter finding differs from the previously published
      studies.

PMID- 25986669
TI  - Occult internal iliac arterial injury identified during open reduction internal
      fixation of an acetabular fracture: a report of two cases.
AB  - We present two cases of occult internal iliac arterial injury identified during
      operative reduction of a widely displaced posterior column posterior wall
      acetabular fracture. This complication was not recognised until reduction of the
      column fracture. There were no preoperative signs or symptoms indicative of a
      vascular injury. These cases emphasise the heightened awareness one must have
      when treating widely displaced posterior column fractures of the acetabulum,
      especially those fractures with extension into the greater sciatic notch, as
      previously formed clot can become dislodged and hemostasis lost. We also present
      management options when this complication occurs. We believe any surgeon treating
      acetabular fractures should be aware of this serious and potentially fatal
      complication. 

PMID- 25986670
TI  - A biomechanical study of standard posterior pelvic ring fixation versus a
      posterior pedicle screw construct.
AB  - OBJECTIVES: The purpose of this study was to biomechanically test a percutaneous
      pedicle screw construct for posterior pelvic stabilisation and compare it to
      standard fixation modalities. METHODS: Utilizing a sacral fracture and sacroiliac
      (SI) joint disruption model, we tested 4 constructs in single-leg stance: an S1
      sacroiliac screw, S1 and S2 screws, the pedicle screw construct, and the pedicle
      screw construct+S1 screw. We recorded displacement at the pubic symphysis and SI
      joint using high-speed video. Axial stiffness was also calculated. Values were
      compared using a 2-way ANOVA with Bonferroni adjustment (p<0.05). RESULTS: In the
      sacral fracture model, the stiffness was greatest for the pedicle screw+S1
      construct (p<0.001). There was no significant difference between the pedicle
      screw construct and S1 sacroiliac screw (p=1). For the SI joint model, the S1+S2
      SI screws had the largest overall load and stiffness (p<0.001). The S1 screw was
      significantly stronger than pedicle screw construct (p=0.001). CONCLUSIONS: The
      pedicle screw construct biomechanically compares to currently accepted methods of
      fixation for sacral fractures when the fracture is uncompressible. It should not
      be used for SI joint disruptions as one SI or an S1+S2 are significantly stiffer
      and cheaper.

PMID- 25986671
TI  - Accuracy of the surgeon's eye: use of the tip-apex distance in clinical practice.
AB  - Tip-apex distance is a well described method for assessment of screw placement in
      dynamic hip screw fixation of proximal femoral fracture. A distance of <25mm is
      associated with a significantly lower rate of cut out of the fixation device.
      Measurement is frequently performed retrospectively, although there has been no
      demonstration as to what accuracy the surgeon has of estimating tip-apex distance
      from image intensifier images, whilst scrubbed in theatre. Thirty-one clinicians
      working within orthopaedic departments were tested in their ability to identify
      adequacy of tip-apex distance on a series of image intensifier images. Level of
      seniority, awareness of the concept of tip-apex distance and use of the concept
      in clinical practice were each assessed. The accuracy in identifying the correct
      TAD was 82.5% in consultants, 83.8% in registrars and 71.1% in Senior house
      officers (SHO). The method was used in clinical practice by 50% of consultants,
      89% of registrars and none of the SHOs.

PMID- 25986672
TI  - [Liver engineering as a new source of donor organs : A systematic review].
AB  - BACKGROUND: Organ engineering is a new strategy to cope with the shortage of
      donor organs. A functional scaffold from explanted organs is prepared by removing
      all cellular components (decellularization) and the reseeding (repopulation) of
      the organ scaffold to generate a functional organ in vitro for transplantation.
      This technique was also applied to the liver (liver engineering). OBJECTIVES:
      Outline of the current state of the art and resulting approaches for future
      research strategies. MATERIAL AND METHODS: Systematic review according to the
      PRISMA guidelines: a PubMed-based literature search (search terms liver,
      decellularization), selection of relevant articles based on predetermined
      criteria for relevance (e.g. decellularization, repopulation and
      transplantation), extraction and critical appraisal of data and results
      concerning the conditions for decellularization, repopulation and
      transplantation. RESULTS: Decellularization was successfully performed in small
      and large animal models. Hepatocytes as well as stem cells and hepatic cell lines
      were applied for repopulation and 7 publications could show the successful
      transplantation of acellular and repopulated organ scaffolds. The current
      scientific need for further studies concerning the source of donor organs,
      optimization of the decellularization process, the cell type for the reseeding
      process and the establishment of the optimal conditions for the repopulation of
      the scaffold is still tremendous. For successful recellularization of the liver
      three goals need to be achieved: (1) reseeding of the organ scaffold with a
      sufficient amount of parenchymal cells, (2) endothelialization of the vascular
      tree to ensure the supply of oxygen and nutrients to parenchymal cells and (3) an
      appropriate epithelialization of the biliary tree. In order to progress to
      clinical trials a suitable transplantation model to verify the function of the
      organ constructs must be established. CONCLUSION: Liver engineering using
      biological cell-free organ scaffolds represents a scientific and ethical
      challenge. The existing results emphasize the potential of this new and promising
      strategy to create organs for transplantation in the future.

PMID- 25986673
TI  - [Complication management following hemorrhoid operations].
AB  - BACKGROUND: Hemorrhoid operations are performed frequently in Germany. After the
      operation severe complications can occur that require appropriate management.
      OBJECTIVE: Presentation of current complications and suitable therapeutic
      options. MATERIAL AND METHODS: Data including operative procedures and
      complications that have been collected in an electronic online-based survey of
      all resident, affiliated and private practice German surgeons during the period
      from 1 December 2009 to 31 January 2010 are presented. A review of the current
      literature in a PubMed search is given. RESULTS: Stapled hemorrhoidopexy has
      several benefits during the early postoperative phase in comparison to
      conventional hemorrhoidectomy; however, patients should be informed about the
      possibility of postoperative defecation disorders, elevated recurrence and
      reoperation rates and rare life-threatening complications. CONCLUSION: The aim
      should be to keep risks at a low level by means of prevention, patient selection,
      careful analysis of indications and relevant expertise. In cases of complications
      early recognition and direct initiation of adequate treatment are crucial.

PMID- 25986674
TI  - [Management of postoperative pancreatic fistula].
AB  - The occurrence of a postoperative pancreatic fistula is one of the most important
      complications following pancreatic resections. The frequency of this complication
      varies between 3 % after pancreatic head resection and up to 35 % following
      distal pancreatectomy. In 2005, the international definition of postoperative
      pancreatic fistula was standardized according to the approach of the
      International Study Group of Pancreatic Surgery (ISGPS) including an A-C grading
      system of the severity. Consequently, results from different studies have become
      comparable and the historically reported fistula rates can be evaluated more
      critically. The present review summarises the currently available data on
      incidence, risk factors, fistula-associated complications and management of
      postoperative pancreatic fistula.

PMID- 25986675
TI  - [Treatment of postoperative impairment of gastrointestinal motility, cholangitis
      and pancreatitis].
AB  - Although the mortality associated with major hepatopancreaticobiliary surgery has
      continuously decreased during the last decades, the morbidity of these procedures
      remains high. Functional disturbances of normal gastrointestinal motility as well
      as inflammation and infections of surgically treated organs are frequent
      complications resulting in considerably prolonged lengths of stay in hospital and
      increased healthcare costs. This review article highlights the therapeutic
      approaches and recent developments in the treatment of delayed gastric emptying,
      prolonged postoperative ileus, postoperative cholangitis and pancreatitis after
      hepatopancreaticobiliary surgery. Current practice is discussed on the basis of
      recent results in basic and clinical research, review articles, meta-analyses and
      guidelines.

PMID- 25986676
TI  - Deletion of the Serotonin Receptor Type 3A in Mice Leads to Sudden Cardiac Death
      During Pregnancy.
AB  - BACKGROUND: The serotonin receptor type 3 (Htr3) blocker is associated with QT
      prolongation and torsades de pointes. However, little is known about effects of
      Htr3 on the heart arrhythmia. METHODS AND RESULTS: An electrophysiological study
      Involving knock-out (KO) female mice lacking functional Htr3a (Htr3a(-/-)) and
      their wild-type littermates during non-pregancy (NP) and late pregnancy (LP) was
      performed. Htr3a mRNA was present in the wild-type, but not in the Htr3a(-/
      )mouse hearts. Serotonin and tryptophan hydroxylase 1 (Tph1), a rate-limiting
      enzyme of serotonin synthesis in hearts, is increased during pregnancy. The heart
      weight and size were increased in the pregnant mice regardless of a mutation. The
      QTc intervals were prolonged after pregnancy in both the wild (NP: 171.2+/-16.8
      vs. LP: 247.7+/-14.3 ms; P<0.001) and Htr3a(-/-)mice (NP: 187.9+/-18.7 vs. LP:
      275.6+/-11.0 ms, P<0.001). Compared with wild-type LP mice, Htr3a(-/-)LP mice had
      increased spontaneous ventricle tarchycardia (VT; 56% vs. 0%, P=0.002), VT
      inducibility (66% vs. 25%, P=0.002) and mortality (56% vs. 0%, P=0.002).
      Pharmacologic administration of serotonin and Htr3 agonists (m-CPBG) decreased
      the QT interval in wild mice, but not in Htr3a(-/-)mice. CONCLUSIONS: Htr3a is
      present in mouse hearts. Serotonin and Tph1 were increased during pregnancy. The
      deletion of Htr3a was related to fatal arrhythmias and sudden cardiac death
      during pregnancy, and its activation reversed the QT prolongation.

PMID- 25986677
TI  - Angiotensin (1-7), small but complicated, needs more exercise.

PMID- 25986678
TI  - Interactions of cyclin-dependent kinase inhibitors AT-7519, flavopiridol and SNS
      032 with ABCB1, ABCG2 and ABCC1 transporters and their potential to overcome
      multidrug resistance in vitro.
AB  - PURPOSE: ATP-binding cassette (ABC) transporters play an important role in
      multidrug resistance (MDR) toward anticancer drugs. Here, we evaluated
      interactions of cyclin-dependent kinase inhibitors (CDKi) AT-7519, flavopiridol
      and SNS-032 with the following ABC transporters in vitro: P-glycoprotein (ABCB1),
      breast cancer resistance protein (ABCG2) and multidrug resistance-associated
      protein 1 (ABCC1). METHODS: Inhibitory potency of studied CDKi to the
      transporters was evaluated by accumulation assays using fluorescent substrates
      and MDCKII cells overexpressing human ABCB1, ABCG2 or ABCC1. Resistance of
      transporter-expressing cells to the CDKi was evaluated by XTT proliferation
      assay. Observed interactions of CDKi were verified by ATPase assay in ABC
      transporter-expressing Sf9 membrane vesicles. Combination index analysis was
      additionally performed in ABC transporter-expressing cancer cell lines, HepG2 and
      T47D. RESULTS: Flavopiridol showed a significant inhibitory potency toward ABCG2
      and ABCC1. SNS-032 also decreased ABCG2-mediated efflux, while AT-7519 failed to
      inhibit ABCB1, ABCG2 or ABCC1. Both flavopiridol and SNS-032 showed synergistic
      antiproliferative effects in combination with relevant ABC transporter substrates
      such as daunorubicin and topotecan in cancer cells. ABCB1 was found to confer
      significant resistance to AT-7519 and SNS-032, but not to flavopiridol. In
      contrast, ABCG2 and ABCC1 conferred resistance to flavopiridol, but not to AT
      7519 and SNS-032. CONCLUSION: Our data provide detailed information on
      interactions of flavopiridol, SNS-032 and AT-7519 with ABC transporters, which
      may help elucidate the pharmacokinetic behavior and toxicity of these compounds.
      Moreover, we show the ability of flavopiridol and SNS-032, but not AT-7519, to
      overcome ABC transporter-mediated MDR.

PMID- 25986679
TI  - Development of a new equation to estimate creatinine clearance in cancer
      patients.
AB  - PURPOSE: Determining renal function is important for chemotherapy eligibility and
      dosing. Measured creatinine clearance (mCrCl) is the gold standard but is
      cumbersome. Equations estimating CrCl (eCrCl) based on serum creatinine (SCr)
      produce widely varying estimates. Considering that SCr is derived from skeletal
      muscle, this study prospectively developed a new eCrCl equation in cancer
      patients using CT-defined muscle surface area (MSA) and evaluated its utility in
      a separate, retrospective series. METHODS: In a prospective, observational cohort
      study of cancer patients, mCrCl by 24-h urine collection was correlated with CT
      determined MSA to create an equation for eCrCl [muscle surface area (cm(2)) *
      42/SCr]. eCrCl by Wright, Cockcroft-Gault (CG), CKD-EPI, MDRD, and MSA was
      compared to mCrCl to determine fit. MSA-eCrCl was used to simulate carboplatin
      dosing in a retrospective series of advanced non-small cell lung cancer (NSCLC).
      RESULTS: Prospectively, 22 patients were accrued and evaluable (12 males; median
      age 69). MSA-eCrCl correlated stronger (r (2) 0.80) than current equations (r (2)
      0.47-0.69) with mCrCl. In calculating carboplatin doses for 89 NSCLC patients
      with MSA and CG-eCrCl, median error of CG-determined carboplatin dose was 5.5 %
      (range -19.0 to 44.2 %), assuming that MSA was better at estimating CrCl. Forty
      two patients (47 %) received doses that varied >=10 % of what was calculated by
      MSA. CONCLUSIONS: We propose a new formula for eCrCl in patients that appears
      more accurate than current formulae and may have implications for chemotherapy
      efficacy and toxicity. Studies to validate this formula are under way.

PMID- 25986680
TI  - ATP-association to intrabacterial nanotransportation system in Vibrio cholerae.
AB  - Vibrio cholerae colonizes the lumen of the proximal small intestine, which has an
      alkaline environment, and secretes cholera toxin (CT) through a type II secretion
      machinery. V. cholerae possesses the intrabacterial nanotransportation system
      (ibNoTS) for transporting CT from the inner portion toward the peripheral portion
      of the cytoplasm, and this system is controlled by extrabacterial pH. Association
      of ATP with ibNoTS has not yet been examined in detail. In this study, we
      demonstrated by immunoelectron microscopy that ibNoTS of V. cholerae under the
      extrabacterial alkaline condition was inhibited by ATP inhibitors, 2,4
      dinitrophenol (DNP), a protonophore, or 8-amino-adenosine which produces inactive
      form of ATP. The inhibition of CT transport can be reversed by neutralization of
      DNP. Those inhibitions were associated with decrease of CT secretion by which
      ibNoTS followed. We propose that ATP closely associates with V. cholerae ibNoTS
      for transporting CT. 

PMID- 25986681
TI  - Double heterozygous mice for Klf5 and Fli1 genes: a new animal model of systemic
      sclerosis recapitulating its three cardinal pathological features.
AB  - The lack of animal models recapitulating the three cardinal features of systemic
      sclerosis (SSc), such as immune activation, vasculopathy, and tissue fibrosis,
      hinders the understanding of the pathogenesis of this disease. A series of
      clinical studies has suggested that environmental factors largely contribute to
      the development of SSc in individuals predisposed by genetic factors. This notion
      is supported by the establishment of a new murine SSc model which recapitulates
      three cardinal features of SSc by simultaneous haploinsufficiency of Klf5 and
      Fli1 genes, both of which are epigenetically suppressed in SSc dermal
      fibroblasts. In addition to enhanced dermal thickness, Klf5(+/-) and Fli1(+/-)
      mice resemble dermal fibrosis of SSc at the ultrastructural level. Furthermore,
      these mice simulate altered vascular structure and B cell activation
      characteristic of SSc. Further studies on the pathological events in Klf5(+/-)
      and Fli1(+/-) mice and the roles of KLF5 and Fli1 in various types of cells may
      provide us with a useful clue to better understand the developmental process of
      SSc.

PMID- 25986682
TI  - Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report
      of a case and review of the literature.
AB  - Paratesticular sarcoma is rare, but liposarcoma is its most common type.
      Paratesticular liposarcoma sometimes presents as dedifferentiated liposarcoma.
      Both high-grade and low-grade dedifferentiation have been reported. Herein, we
      presented a unique case of a 64-year-old man with low-grade dedifferentiated
      liposarcoma with prominent myxoid stroma. Well-differentiated liposarcoma
      components extended along the spermatic cord. The constituent cells of the
      dedifferentiated component were peculiar in that, they were relatively uniform
      cells with atypia and did not have pleomorphism to such an extent that it
      mimicked myxofibrosarcoma. This myxoid component was confidently differentiated
      from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4
      and MDM2. These two markers were also expressed in the well-differentiated
      component. It could therefore be confirmed that this sarcoma is dedifferentiated
      liposarcoma but is not mixed-type liposarcoma comprising well-differentiated
      liposarcoma and myxoid liposarcoma.

PMID- 25986683
TI  - Infrapatellar fat pad preservation reduces wound complications after minimally
      invasive total knee arthroplasty.
AB  - INTRODUCTION: The aim of this study was to determine whether pain intensity and
      wound complication rates differ between patients with and without preservation of
      the infrapatellar fat pad (IPFP) after minimally invasive total knee arthroplasty
      (TKA). The authors also sought to determine whether IPFP preservation affects
      operation time. MATERIALS AND METHODS: This retrospective study included 448
      knees with primary TKA. The IPFP was totally resected in 201 knees (IPFP-R
      group), and was preserved in 247 knees (IPFP-P group). Pain score was determined
      using the visual analog scale during the first 72 h after surgery. Wound
      complication rates and operation times were also evaluated. A wound complication
      was defined as persistent wound drainage for three or more days after surgery.
      RESULTS: There was no difference in pain levels between the two groups. However,
      there were fewer wound complications in the IPFP-P group (3 %) than in the IPFP-R
      group (13 %). The operation time was longer in the IPFP-P group than in the IPFP
      R group (70 vs. 64 min, respectively). CONCLUSIONS: Although IPFP preservation
      delayed operation time, it decreased wound complications after MIS TKA. These
      findings are important to consider when deciding whether or not to resect the
      IPFP. Whenever possible, IPFP preservation is probably the preferred technique to
      reduce wound complications.

PMID- 25986684
TI  - In vitro and in vivo toxicity of 5-FdU-alendronate, a novel cytotoxic bone
      seeking duplex drug against bone metastasis.
AB  - BACKGROUND: Bone remains one of the most common anatomic sites for cancer
      metastases, and the limited therapeutic options aggravate cancer-related
      morbidity and mortality in multiple malignancies. The covalent conjugation of the
      amino-bisphosphonate alendronate (ale) with the antimetabolite 5-fluoro-2'
      desoxyuridine (5-FdU) results in N(4)-(butyl-(4-hydroxy-4-phosphono)phosphate)-5
      fluoro-2'-desoxyuridine (5-FdU-alendronat, 5-FdU-ale), an effective, novel bone
      targeting duplex drug directed against skeletal cancer manifestations. METHODS:
      In vitro cytotoxicity of ale, 5-FdU or 5-FdU-ale was measured with Alamar Blue
      and MUH cell viability assays in 14 malignant melanoma, multiple myeloma, bone
      marrow-derived stromal cell and osteoblast-like cell lines. In vivo toxicity was
      evaluated using the chicken embryo assay and evaluation of nephrotoxicity and the
      systemic toxicity in Balb/c nude mice. The effect of 5-FdU-ale on osteoclast was
      evaluated with Balb/c nude mice in a metastatic breast cancer mouse model.
      RESULTS: A cell line-specific, dose-related cytotoxicity was observed for 5-FdU
      ale in all cancer cell lines tested, which was significantly less toxic than 5
      FdU alone when compared to the benign osteoblasts or stromal cells. The
      embryotoxicity of 5-FdU-ale was significantly less than that of the parental
      drugs alendronate or 5-FdU. 5-FdU-ale showed no signs of unwanted side effects,
      weight loss or nephrotoxicity in mice. In a bone metastasis mouse model, 5-FdU
      ale reduced the number of tumor-associated osteoclasts. CONCLUSION: The coupling
      of an amino-bisphosphonate with an antimetabolite via an N-alkyl-bonding offers a
      new strategy for the preparation of amino-bisphosphonates conjugates with a
      cancer cell-specific, efficacious cytotoxic bone-targeting potential along with a
      reduced systemic toxicity. The innovative duplex drug 5-FdU-ale therefore
      warrants further clinical investigation.

PMID- 25986685
TI  - From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic
      Implications.
AB  - PAR1, member of the family of protease-activated receptors, is a GPCR whose
      activation requires a proteolytic cleavage at its extracellular N-terminus to
      unveil a tethered activating ligand. Although thrombin is the main activator of
      this receptor, diverse other proteases can also activate and disarm PAR1.
      Besides, tethered activating ligand-based peptides (PAR-APs) can also activate
      the receptor. PAR1 mainly signals via G proteins but, it can also signal using
      beta-arrestin pathways and by transactivation of other receptors. This complex
      PAR1 interactome is completed with the receptor desensitization, trafficking, and
      degradation. PAR1 has shown species-, cellular-, and physiological or
      pathological state-dependent specificity. This review try to give an overview on
      the complex PAR1 interactome, its therapeutic impact upon the cardiovascular,
      immune and nervous systems, inflammation and cancer, as well as, on its
      modulation with agonists and antagonists. 

PMID- 25986686
TI  - The Role of Water Occlusion for the Definition of a Protein Binding Hot-Spot.
AB  - Biological systems rely on the establishment of interactions between
      biomolecules, which take place in the aqueous environment of the cell. It was
      already demonstrated that a small set of residues at the interface, Hot
      Spots(HS), contributes significantly to the binding free energy. However, these
      energetic determinants of affinity and specificity are still not fully
      understood. Moreover, the contribution of water to their HS character is also
      poorly characterized. In this review, we have focused on the structural data
      available that support the occlusion of HS from solvent, and therefore the "O
      ring theory"not only on protein-protein but also on protein-DNA complexes. We
      also emphasized the use of Solvent Accessible Surface Area (SASA) features in a
      variety of machine-learning approaches that aim to detect binding HS.

PMID- 25986687
TI  - Targeting Protein-Protein Interactions in the Proteasome Super-Assemblies.
AB  - Protein-protein interactions (PPI) are at the center of molecular mechanisms of
      life. The protein ligands convene for regulation of biological function: adding,
      enhancing or inhibiting activity, for assistance in structural integrity or to
      enable subsequent PPI. All these general roles of PPI are represented in the
      proteasome, the giant proteolytic factory universally present in human cells. The
      proteasome is a renowned target for anti-cancer drugs and a considered target for
      drugs curbing inflammation. The essential function of the proteasome, the
      degradation of a majority of intracellular proteins via the ubiquitin-proteasome
      pathway, relies on proper interactions between multiple subunits of the enzyme
      and between multiple modules forming distinct super-assemblies covered by the
      "proteasome" name. The interface regions between constitutive, alternative or
      transient protein components of the proteasome provide a rich platform for design
      of drugs with potentially very diverse actions. Still, the resource remains
      largely untapped since all proteasome-targeting drugs used so far in humans are
      classical competitive inhibitors blocking catalytic centers. In this review, we
      will discuss the opportunities and challenges of targeting PPI in the hub enzyme
      for intracellular protein catabolism, the proteasome.

PMID- 25986688
TI  - The Dynamics of Drug Discovery.
AB  - Proteins are not static objects. To carry out their functions in the cells and
      participate in biochemical interaction networks, proteins have to explore
      different conformational substates, which favor the adaptation to different
      partners and ultimately allow them to respond to changes in the environment. In
      this paper we discuss the implications of including the atomistic description of
      protein dynamics and flexibility in the context of drug discovery and design. The
      underlying idea is that a better understanding of the atomistic details of
      molecular recognition phenomena and conformational cross-talk between a ligand
      and a receptor can in fact translate in unexplored opportunities for the
      discovery of new drug like molecules. We will illustrate and discuss dynamics
      based pharmacophores, the discovery of cryptic binding sites, the
      characterization and exploitation of allosteric regulation mechanisms and the
      definition of potential protein-protein interaction sites as potential sources of
      new bases for the rational design of small molecules endowed with specific
      biological functions. Overall, the inclusion of protein flexibility in the drug
      discovery process is starting to attract attention not only in the academic but
      also in the industrial community. This is supported by experimental tests that
      prove the actual feasibility of considering the explicit dynamics of drug-protein
      interactions at all relevant levels of resolution and the use of multiple
      receptor conformations in drug discovery, as affordable complements (if not an
      alternative) to classical High Throughput Screening (HTS) efforts based on static
      structures.

PMID- 25986690
TI  - From Protein Communication to Drug Discovery.
AB  - The majority of functionally important biological processes are regulated by
      allosteric communication within individual proteins and across protein complexes.
      The proteins controlling these communication networks respond to changes in the
      cellular environment by switching between different conformational states.
      Targeting the interface residues mediating these processes through the rational
      identification of molecules modulating or mimicking their effects holds great
      therapeutic potential. Protein-protein interactions (PPIs) have shown to have a
      high degree of plasticity since they occur through small regions, called hot
      spots, which are included in binding surfaces or in binding clefts of the
      proteins and are characterized by a high degree of complementarity. This prompted
      several researchers to compare the protein structure to human grammar proposing
      terms like "protein language". The decoding of this language represent a new
      paradigm not only to clarify the dynamics of many biological processes but also
      to improve the opportunities in drug discovery. In this review, we try to give an
      overview on intra-molecular and inter-molecular protein communication mechanisms
      describing the protein interaction domains (PIDs) and short linear motifs
      (SLiMs), which delineate the authentic syntactic and semantic units in a protein.
      Moreover, we illustrate some novel approaches performed on natural compounds and
      on synthetic derivatives aimed at developing new classes of potential drugs able
      to interfere with intra-molecular and inter-molecular protein communication. 

PMID- 25986691
TI  - Taming Oncogenic Signaling at Protein Interfaces: Challenges and Opportunities.
AB  - Many key cellular events determining the thin line between healthy and oncogenic
      behavior rely on the proper functioning of protein-protein interactions (PPIs).
      Alterations that affect the affinity of a protein-protein binding site may
      destabilize a desired healthy interaction, or stabilize an oncogenic interaction.
      The understanding that there are a few key hot-spot residues that are mainly
      responsible for the binding energy of an interaction greatly widened the
      prospects of targeting oncogenic protein-protein interfaces enabling the use of
      small ligands in addition to biological molecules such as peptides and
      antibodies. Taming oncogenic signaling requires a deep understanding of protein
      interactions and their networks. Traditional representation of PPIs in signaling
      pathways as nodes and edges falls short of expressing interaction specific
      modulation of signals. Structural networks, deciphering which sites on a protein
      structure are responsible for each of the many interactions it may carry out,
      help understanding specific oncogenic mutations on signaling. We describe the key
      features of PPIs and their targeting, together with the advantages of structural
      networks, and provide four case studies demonstrating different opportunities for
      the aim of modulating oncogenic interactions. 

PMID- 25986689
TI  - High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the
      Identification of PPIs Antagonists.
AB  - In recent years the ever so complex field of drug discovery has embraced novel
      design strategies based on biophysical fragment screening (fragment-based drug
      design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or
      structure-guided approaches, most often using X-ray crystallography and computer
      modeling. Experience from recent years unveiled that these methods are more
      effective and less prone to artifacts compared to biochemical high-throughput
      screening (HTS) of large collection of compounds in designing protein inhibitors.
      Hence these strategies are increasingly becoming the most utilized in the modern
      pharmaceutical industry. Nonetheless, there is still an impending need to develop
      innovative and effective strategies to tackle other more challenging targets such
      as those involving protein-protein interactions (PPIs). While HTS strategies
      notoriously fail to identify viable hits against such targets, few successful
      examples of PPIs antagonists derived by FBDD strategies exist. Recently, we
      reported on a new strategy that combines some of the basic principles of fragment
      based screening with combinatorial chemistry and NMR-based screening. The
      approach, termed HTS by NMR, combines the advantages of combinatorial chemistry
      and NMR-based screening to rapidly and unambiguously identify bona fide
      inhibitors of PPIs. This review will reiterate the critical aspects of the
      approach with examples of possible applications. 

PMID- 25986692
TI  - Hepatoid carcinoma of the pancreas.
AB  - BACKGROUND: Hepatoid carcinoma of the pancreas is extremely rare. This article
      tries to summarize the clinical features and outcomes of pancreatic hepatoid
      carcinoma. METHODS: The data pool for analysis includes the case we encountered
      with hepatoid carcinoma of the pancreas and the reported cases in the literature.
      RESULTS: Twenty-three cases of hepatoid carcinoma of the pancreas were analyzed.
      This tumor occurred more frequently in male than in female patients (69.6 vs.
      30.4 %). Tumor sizes range from 0.5 to 11.0 cm with median of 6.0 cm. The most
      common symptom was epigastric pain (36.4 %). When the tumor locates at pancreatic
      head, nausea/vomiting (62.5 %) is more common, followed by jaundice and
      epigastric pain (50.0 %). For those at pancreatic body-tail, 42.9 % of the
      patients presented no symptom. Alpha-fetoprotein (AFP) was abnormally elevated in
      60 % of the cases. Hepatoid carcinoma in the pancreas could be either pure form
      or mixed form with other malignancy (40.9 %), with the most common coexisted
      pathology of malignant neuroendocrine tumor (22.7 %). Metastasis occurred in 36.4
      % of the cases at the diagnosis of this tumor, including liver metastasis in 31.8
      % and lymph node metastasis in 21.1 %. The overall 1-year survival rate was 71.1
      % and 5-year 40.4 %, with a median of 13.0 months. Unresectability, hepatic, and
      lymph node metastases are associated with negative impact on survival outcome.
      CONCLUSIONS: Elevation of serum AFP may be a clue leading to the diagnosis of
      pancreatic hepatoid carcinoma. This tumor could be mixed form with other
      malignancy. Surgical resection should be the treatment of choice whenever
      possible.

PMID- 25986696
TI  - D-Amphetamine withdrawal-induced decreases in brain-derived neurotrophic factor
      in sprague-dawley rats are reversed by treatment with ketamine.
AB  - Withdrawal from chronic D-amphetamine (D-AMPH) can induce negative emotional
      states, which may contribute to relapse and the maintenance of addiction.
      Diminished levels of brain-derived neurotrophic factor (BDNF), particularly in
      the hippocampus has been observed after exposure to stress, and recent data
      indicate that treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist,
      ketamine may reverse these changes. However, it is unclear whether BDNF levels in
      the hippocampus or other regions of the limbic system are altered following the
      stress of D-AMPH withdrawal and it is not currently known if treatment with
      ketamine has any effect on these changes. The goals of this study were to examine
      BDNF levels throughout the limbic system following D-AMPH withdrawal and
      determine whether ketamine treatment would alter D-AMPH-induced changes in BDNF.
      Sprague-Dawley rats were treated with D-AMPH and BDNF protein examined in the
      prefrontal cortex, nucleus accumbens, amygdala and hippocampus at 24 h and 4 days
      of withdrawal. Our data show that at 24 h post-D-AMPH, BDNF levels were increased
      in the nucleus accumbens and decreased in the hippocampus. At 4 d post-D-AMPH,
      BDNF protein levels were decreased in all areas examined, and these decreases
      were reversed by treatment with ketamine. These data suggest that diminished BDNF
      may contribute to the negative affect seen following D-AMPH withdrawal, and that
      ketamine treatment could offer relief from these symptoms.

PMID- 25986693
TI  - Corrole and nucleophilic aromatic substitution are not incompatible: a novel
      route to 2,3-difunctionalized copper corrolates.
AB  - The insertion of a -NO2 group onto the corrole framework represents a key step
      for subsequent synthetic manipulation of the macrocycle based on the chemical
      versatility of such a functionality. Here we report results of the investigation
      of a copper 3-NO2-triarylcorrolate in nucleophilic aromatic substitution
      reactions with "active" methylene carbanions, namely diethyl malonate and diethyl
      2-chloromalonate. Although similar reactions on nitroporphyrins afford chlorin
      derivatives, nucleophilic attack on carbon-2 of corrole produces 2,3
      difunctionalized Cu corrolates in acceptable yields (ca. 30%), evidencing once
      again the erratic chemistry of this contracted porphyrinoid. 

PMID- 25986694
TI  - Eukaryotic translation elongation factor-1 alpha is associated with a specific
      subset of mRNAs in Trypanosoma cruzi.
AB  - BACKGROUND: Regulation of gene expression in trypanosomatids is mainly
      posttranscriptional. Tight regulation of mRNA stability and access to polysomes
      allows Trypanosoma cruzi to adapt to different environmental conditions during
      its life cycle. Posttranscriptional regulation requires association between mRNAs
      and specific proteins to form mRNP complexes. Proteins that lack a canonical RNA
      binding domain, such as eukaryotic elongation factor-1alpha (EF-1alpha), may also
      associate with mRNPs. EF-1alpha is conserved in many organisms, and it plays
      roles in many cellular processes other than translation, including RNA transport,
      the cell cycle, and apoptosis. RESULTS: In a previous study, EF-1alpha was found
      associated with mRNP-forming mRNAs in polysome-free fractions both in
      epimastigotes growing under normal conditions and in nutritionally stressed
      parasites. This finding suggested the possibility that EF-1alpha has a non
      canonical function. Thus, we investigated the dynamics of EF-1alpha in
      association with T. cruzi epimastigote mRNAs under normal and stressed
      nutritional conditions. EF-1alpha is expressed throughout the parasite life
      cycle, but it shows a slight decrease in protein levels in the metacyclic
      trypomastigote form. The protein is cytoplasmically localized with a granular
      pattern in all forms analyzed. Following puromycin treatment, EF-1alpha migrated
      with the heaviest gradient fractions in a sucrose polysome profile, indicating
      that its association with large protein complexes was independent of the
      translation machinery. We next characterized the EF-1alpha-associated mRNAs in
      unstressed and stressed epimastigotes. We observed that specific subsets of mRNAs
      were associated with EF-1alpha-mRNPs in unstressed or stressed epimastigotes.
      Some mRNAs were identified in both physiological conditions, whereas others were
      condition-specific. Gene ontology analysis identified enrichment of gene sets
      involved in single-organism metabolic processes, amino acid metabolic processes,
      ATP and metal ion binding, glycolysis, glutamine metabolic processes, and cobalt
      and iron ion binding. CONCLUSION: These results indicate that in T. cruzi, as in
      other eukaryotes, EF-1alpha may play a non-canonical cellular role. We observed
      the enrichment of functionally related transcripts bound to EF-1alpha in normal
      growth conditions as well as in nutritionally stressed cell indicating a
      potential role of EF-1alpha mRNP in stress response.

PMID- 25986697
TI  - The histamine H4-receptor and the central and peripheral nervous system: A
      critical analysis of the literature.
AB  - Expression and function of histamine H4R in central and peripheral nervous system
      have been a matter of controversy for more than a decade. The scientific
      discussion is often limited to a few publications postulating the presence of
      functional H4R on neurons of the central and peripheral nervous system, but the
      even larger number of reports showing negative data is often neglected. In this
      article, we critically review the existing literature on H4R in central and
      peripheral nervous system and discuss the weak points often overlooked by the
      community. We identified as most important problems (i) insufficient validation
      or quality of antibodies, (ii) missing knockout controls, (iii) uncritical
      interpretation of RT-PCR results instead of qPCR experiments, (iv) insufficient
      controls to confirm specificity of pharmacological tools, (v) uncritical reliance
      on results produced by a single method and (vi) uncritical reliance on results
      not reproduced by independent research groups. Additionally, there may be a
      publication as well as a citation bias favoring the awareness of positive
      results, but neglecting negative data. We conclude that H4R expression on neurons
      of the brain is not convincingly supported by the current literature, at least as
      long as the positive data are not reproduced by independent research groups.
      Expression and function of H4R on peripheral neurons or non-neuronal cells of the
      nervous system, specifically on microglia is an interesting alternative
      hypothesis that, however, requires further verification. This article is part of
      a Special Issue entitled 'Histamine Receptors'.

PMID- 25986699
TI  - A pilot effectiveness study of the Enhancing Parenting Skills (EPaS) 2014
      programme for parents of children with behaviour problems: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: The Enhancing Parenting Skills (EPaS) 2014 programme is a home-based,
      health visitor-delivered parenting support programme for parents of children with
      identified behaviour problems. This trial aims to evaluate the effectiveness of
      the EPaS 2014 programme compared to a waiting-list treatment as usual control
      group. METHODS/DESIGN: This is a pragmatic, multicentre randomised controlled
      trial. Sixty health visitors will each be asked to identify two families that
      have a child scoring above the clinical cut-off for behaviour problems using the
      Eyberg Child Behaviour Inventory (ECBI). Families recruited to the trial will be
      randomised in a 1:1 ratio into an intervention or waiting-list control group.
      Randomisation will occur within health visitor to ensure that each health visitor
      has one intervention family and one control family. The primary outcome is change
      in child behaviour problems as measured by the parent-reported ECBI. Secondary
      outcomes include other measures of child behaviour, parent behaviour, and
      parental depression as measured by parent-reports and an independent observation
      of parent and child behaviour. Follow-up measures will be collected 6-months
      after the collection of baseline measures. DISCUSSION: This is the first rigorous
      evaluation of the EPaS 2014 programme. The trial will provide important
      information on the effectiveness of a one-to-one home-based intervention,
      delivered by health visitors, for pre-school children with behaviour problems. It
      will also examine potential mediating (improved parent behaviour and/or improved
      parental depression) and moderating (single parent, teenage parent, poverty, low
      education level) factors. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN06867279 (18 June 2014).

PMID- 25986698
TI  - Mouse model of OPRM1 (A118G) polymorphism has altered hippocampal function.
AB  - A single nucleotide polymorphism (SNP) in the human MU-opioid receptor gene
      (OPRM1 A118G) has been widely studied for its association in a variety of drug
      addiction and pain sensitivity phenotypes; however, the extent of these
      adaptations and the mechanisms underlying these associations remain elusive. To
      clarify the functional mechanisms linking the OPRM1 A118G SNP to altered
      phenotypes, we used a mouse model possessing the equivalent nucleotide/amino acid
      substitution in the Oprm1 gene. In order to investigate the impact of this SNP on
      circuit function, we used voltage-sensitive dye imaging in hippocampal slices and
      in vivo electroencephalogram recordings of the hippocampus following MOPR
      activation. As the hippocampus contains excitatory pyramidal cells whose activity
      is highly regulated by a dense network of inhibitory neurons, it serves as an
      ideal structure to evaluate how putative receptor function abnormalities may
      influence circuit activity. We found that MOPR activation increased excitatory
      responses in wild-type animals, an effect that was significantly reduced in
      animals possessing the Oprm1 SNP. Furthermore, in order to assess the in vivo
      effects of this SNP during MOPR activation, EEG recordings of hippocampal
      activity following morphine administration corroborated a loss-of-function
      phenotype. In conclusion, as these mice have been shown to have similar MOPR
      expression in the hippocampus between genotypes, these data suggest that the MOPR
      A118G SNP results in a loss of receptor function. 

PMID- 25986701
TI  - Synchronous double primary squamous cell carcinoma and adenocarcinoma of the
      extrahepatic bile duct: a case report.
AB  - INTRODUCTION: Synchronous double cancers of the bile duct are exceptionally rare.
      We here report a case of synchronous squamous cell carcinoma and adenocarcinoma
      of the extrahepatic bile duct. CASE PRESENTATION: A 67-year-old Asian man visited
      our clinic complaining of jaundice and dark urine. Direct hyperbilirubinemia and
      an elevated cancer antigen 19-9 level were detected. Preoperative abdominal
      computed tomography and positron emission tomography showed two masses at the
      bifurcation of the common hepatic duct and at the distal common bile duct. After
      biliary drainage, we performed radical pylorus-preserving
      pancreaticoduodenectomy, without resection margin involvement. Pathological
      findings revealed that the proximal lesion was a squamous cell carcinoma and that
      the distal lesion was an adenocarcinoma. Both cholangiocarcinomas were confined
      to the fibromuscular layer, and there was no communication between the two
      tumors. Multiple conglomerated metastatic tumors were detected in his liver 3
      months after surgery. He died 8 months after diagnosis. CONCLUSIONS: The disease
      displayed very aggressive behavior and a very poor prognosis. The only chance for
      long-term survival is treatment with radical resection. Preoperative positron
      emission tomography-computed tomography is useful in detecting occult cancer.

PMID- 25986705
TI  - European College of Orthodontics: Commission of Affiliation and Titularisation.
AB  - Date of birth: 16/10/1989; sex: male. A. PRE-TREATMENT RECORDS: 20.3 years;
      14/01/2010. DIAGNOSIS: Angle class: Class I, tooth arch discrepency, bi-maxillary
      protrusion. Missing teeth before treatment: wisdom teeth extracted before
      treatment. TREATMENT PLAN: Appliances or means used: lingual multi-banded. Start
      of treatment 20.4 years; 25/02/2010. B. POST-TREATMENT RECORDS: 22.5 years;
      24/03/2012. DURATION OF ACTIVE TREATMENT: 25 months. RETENTION: Maxillary fixed 5
      5; mandibular: fixed 5-5. C. POST-RETENTION RECORDS: (minimum 1 year): 23.6
      years; 22/04/2013. Duration of retention: 13 months.

PMID- 25986702
TI  - Association between facial growth pattern and facial muscle activity: A
      prospective cross-sectional study.
AB  - OBJECTIVE: To evaluate the relationship between facial growth pattern and
      electromyography (EMG) of facial muscles: anterior temporalis, masseter,
      buccinators, orbicularis oris, mentalis and anterior digastric. PATIENTS AND
      METHODS: The sample consisted of 77 subjects aged between 18-28 years (mean age
      21.10+/-2.03), with dental Class I relationship, normal overjet and overbite,
      balanced facial profile, no signs of temporomandibular disorders, and no previous
      orthodontic treatment. Facial growth pattern was determined on the lateral
      cephalograms according to the Bjork sum (sum of the N-S-Ar, S-Ar-Go, and Ar-Go-Me
      angles) dividing the sample into three groups: horizontal facial pattern group
      (24 subjects), normal facial pattern group (41 subjects), and vertical facial
      pattern group (12 subjects). The EMG of anterior temporalis, masseter,
      buccinator, orbicularis oris, mentalis and anterior digastric muscles were
      examined for each patient in the rest position and in functional positions
      (central maximum intercuspation, chewing on right side, chewing on left side and
      swallowing). Mean values and standard deviation of EMG were obtained and compared
      between the three groups. RESULTS: At rest, the EMG of the masseter, orbicularis
      oris and anterior digastric were higher in the vertical facial pattern group
      compared with the other two groups, with a moderate positive correlation between
      the EMG of these muscles and the Bjork sum (P<.01). In contrast, during central
      maximum intercuspation, the activity of the anterior temporalis, masseter and
      buccinator was significantly lower in the vertical facial pattern group compared
      with the two other groups, with a moderate negative correlation between the Bjork
      sum and EMG in the maximum central intercuspation position of these muscles
      (P<.01). CONCLUSIONS: A significant relationship was found between facial muscle
      activity and facial growth pattern. The findings suggest that the activity of
      masticatory and perioral muscles could play a role in the direction of the facial
      growth.

PMID- 25986700
TI  - Tissue inflammation and nitric oxide-mediated alterations in cardiovascular
      function are major determinants of endotoxin-induced insulin resistance.
AB  - BACKGROUND: Endotoxin (i.e. LPS) administration induces a robust inflammatory
      response with accompanying cardiovascular dysfunction and insulin resistance.
      Overabundance of nitric oxide (NO) contributes to the vascular dysfunction.
      However, inflammation itself also induces insulin resistance in skeletal muscle.
      We sought to investigate whether the cardiovascular dysfunction induced by
      increased NO availability without inflammatory stress can promote insulin
      resistance. Additionally, we examined the role of inducible nitric oxide synthase
      (iNOS or NOS2), the source of the increase in NO availability, in modulating LPS
      induced decrease in insulin-stimulated muscle glucose uptake (MGU). METHODS: The
      impact of NO donor infusion on insulin-stimulated whole-body and muscle glucose
      uptake (hyperinsulinemic-euglycemic clamps), and the cardiovascular system was
      assessed in chronically catheterized, conscious mice wild-type (WT) mice. The
      impact of LPS on insulin action and the cardiovascular system were assessed in WT
      and global iNOS knockout (KO) mice. Tissue blood flow and cardiac function were
      assessed using microspheres and echocardiography, respectively. Insulin signaling
      activity, and gene expression of pro-inflammatory markers were also measured.
      RESULTS: NO donor infusion decreased mean arterial blood pressure, whole-body
      glucose requirements, and MGU in the absence of changes in skeletal muscle blood
      flow. LPS lowered mean arterial blood pressure and glucose requirements in WT
      mice, but not in iNOS KO mice. Lastly, despite an intact inflammatory response,
      iNOS KO mice were protected from LPS-mediated deficits in cardiac output. LPS
      impaired MGU in vivo, regardless of the presence of iNOS. However, ex vivo,
      insulin action in muscle obtained from LPS treated iNOS KO animals was protected.
      CONCLUSION: Nitric oxide excess and LPS impairs glycemic control by diminishing
      MGU. LPS impairs MGU by both the direct effect of inflammation on the myocyte, as
      well as by the indirect NO-driven cardiovascular dysfunction.

PMID- 25986706
TI  - Cervico-facial irradiation and orthodontic treatment.
AB  - Cancers during infancy and childhood affect 1 to 3% of children under the age of
      15. Among these cancers the most frequent are malignant hemopathies, and in
      particular, acute lymphoblastic leukemia, which represents 80% of infant
      leukemias, with a peak of incidence around the age of 3-4. The overall prognosis
      for infant malignant hemopathies has improved significantly thanks to progress
      made in chemotherapy and radiotherapy. However, these anti-cancer treatments,
      particularly radiotherapy, when performed early, generally before 5 years of age,
      can have harmful effects that interfere with overall growth and particularly
      cranio-facial growth, and also with the child's oro-dental development. Some
      effects such as mandibular retrognathia, macrodontia, microdontia, agenesis and
      delayed eruption could increase the need for orthodontic treatment, while other
      complications, particularly the reduced height of the alveolar processes, short
      thin roots and modification of the superficial and profound periodontium, are
      likely to make such treatment more difficult. The aim of this review of the
      literature is to identify the essential factors that must be analyzed before
      orthodontic treatment is proposed for subjects who have undergone radiotherapy at
      an early age, and the precautions to be taken before and during orthodontic
      treatment. 

PMID- 25986707
TI  - Recovering teeth from a large dentigerous cyst: A case report.
AB  - A dentigerous cyst is an odontogenic lesion caused by the expansion of the
      follicle surrounding the crown of impacted, embedded or unerupted teeth. These
      cysts may cause destruction of the bone, displacement of adjacent teeth,
      resorption of their roots and prevent the eruption of cyst-associated permanent
      teeth. This paper discusses successful use of marsupialization combined with
      orthodontic treatment to treat cyst-associated impacted permanent teeth and to
      correct a class II open bite malocclusion.

PMID- 25986708
TI  - Influence of tonsil size on sagittal cephalometric measurements.
AB  - INTRODUCTION: The role of tonsils in the origin of sagittal skeletodental
      abnormalities has been widely discussed in the literature but remains
      controversial. Data on the probable relationship between enlarged tonsils and the
      presence of these abnormalities were subjective. The aim of this study was to
      quantify the relationship between the space occupied by the palatine tonsils and
      sagittal cephalometric measurements. MATERIALS AND METHODS: A cross-sectional
      study was performed on a group of children divided into 5 subgroups according to
      the standardized tonsillar hypertrophy grading scale. Cephalometric measurements
      were recorded for each child. Data were analyzed using SPSS 20.0 for Windows. The
      strength of the association between tonsil grades and quantitative variables was
      assessed using Spearman's rank correlation coefficient (Rho). The level of
      significance was fixed at P=0.05. RESULTS: Lengths SN, t2-p3, h-Gn and Xi-pm, and
      angles I/F, I/SN, i/M, SNB, SNPog and SNGn were significantly and negatively
      correlated with grades. The ANB angle, the sagittal position of the pogonion and
      the angle of facial convexity were significantly and positively correlated with
      grades. CONCLUSION: Early evaluation of tonsil size can prevent certain
      skeletodental abnormalities in the sagittal plane caused by upper airway
      obstruction. Thus, more aggressive late treatments, which are not always as
      effective as when they are performed during childhood, can be avoided.

PMID- 25986710
TI  - Esthetic evaluation of dental and gingival asymmetries.
AB  - The aim of this study was to determine which smile asymmetries were less
      esthetic, dental or gingival. MATERIAL AND METHODS: Laypeople (297), generalists
      (223), prosthodontists (50) and orthodontists (49), evaluated the esthetics of
      digitally-modified images taken from the same frontal intra-oral photograph,
      using the same lips, simulating upper maxillary midline shift, occlusal plane
      inclination, asymmetric incisal edge and asymmetric gingival migration. The
      images were later paired into 3 groups. RESULTS: The only ones considered
      esthetic were the asymmetric incisal edge of the 0.5 mm shorter upper central
      incisor and the asymmetric gingival migration (2 mm) of the upper central
      incisor. In the paired images, upper maxillary midline shift vs. occlusal plane
      inclination, the former was rated less esthetic, while in the asymmetric incisal
      edge vs. asymmetric gingival migration pair, the latter was considered to be less
      esthetic. CONCLUSION: Laypeople and generalists consider smiles more attractive.
      The only images considered esthetic were the asymmetric incisal edge of the
      central incisor shorter by 0.5 mm and the 2 mm asymmetric gingival migration of
      the upper central incisor. In the horizontal plane (maxillary midline shift vs.
      occlusal plane cant), the dental asymmetries were considered less esthetic than
      the gingival asymmetries. However, in the vertical plane (asymmetric incisal edge
      vs. asymmetric gingival migration) the opposite was recorded.

PMID- 25986714
TI  - The social context of severe child malnutrition: a qualitative household case
      study from a rural area of the Democratic Republic of Congo.
AB  - INTRODUCTION: The magnitude of child malnutrition including severe child
      malnutrition is especially high in the rural areas of the Democratic Republic of
      Congo (the DRC). The aim of this qualitative study is to describe the social
      context of malnutrition in a rural part of the DRC and explore how some
      households succeed in ensuring that their children are well-nourished while
      others do not. METHODOLOGY: This study is based on participant observation, key
      informant interviews, group discussions and in-depth interviews with four
      households with malnourished children and four with well-nourished children. We
      apply social field theory to link individual child nutritional outcomes to
      processes at local level and to the wider socio-economic environment. FINDINGS:
      We identified four social fields that have implications for food security and
      child nutritional outcomes: 1) household size and composition which determined
      vulnerability to child malnutrition, 2) inter-household cooperation in the form
      of 'gbisa work party' which buffered scarcity of labour in peak seasons and
      facilitated capital accumulation, 3) the village associated with usufruct rights
      to land, and 4) the local NGO providing access to agricultural support, clean
      drinking water and health care. CONCLUSIONS: Households that participated in
      inter-household cooperation were able to improve food and nutrition security.
      Children living in households with high pressure on productive members were at
      danger of food insecurity and malnutrition. Nutrition interventions need to
      involve local institutions for inter-household cooperation and address the
      problem of social inequalities in service provision. They should have special
      focus on households with few resources in the form of land, labour and capital.

PMID- 25986716
TI  - Genetics: Beyond susceptibility--predictors of prognosis and response in RA.

PMID- 25986715
TI  - Overexpressions of DLL4 and CD105 are Associated with Poor Prognosis of Patients
      with Pancreatic Ductal Adenocarcinoma.
AB  - The aim of this study was to investigate the expression of Delta-like ligand
      4(DLL4) and Endoglin(CD105) labeled microvessel density(MVD) in pancreatic ductal
      adenocarcinoma (PDAC) and evaluate their correlation with major clinicopathologic
      features and patients' survival. Forty-two pancreatic cancer and 20 normal
      pancreatic tissues were included in the study. Immunohistochemical staining was
      employed to assess the expression level of DLL4 both in tumor cells and stromal
      vascular endothelial cells, as well as CD105 which was used to determine MVD. The
      relationships of DLL4 and CD105 expression with clinicopathologic parameters and
      clinical outcome were evaluated. Both DLL4 and CD105-labeled microvessel were
      observed highly immunostained in PDAC cases, and high expression of DLL4 was
      positively correlated with MVD. Moreover, the high expression of DLL4 was
      significantly associated with histological grade, node stage and TNM stage in not
      only the cancer cells but also stroma; while high expression of CD105 was
      associated with histological grade, TNM stage, node stage and distant metastasis.
      In univariant analysis, patients with high expression of DLL4 and CD105 tended to
      significantly poorer overall survival. Both DLL4 and CD105 were overexpressed in
      a large proportion of patients with PDAC. The expression of DLL4 was positively
      correlated with CD105-labeled MVD, indicating DLL4 may involved in angiogenesis.
      In addition, high DLL4 and CD105 expression correlated with the poor clinical
      outcome and overall survival in patients with PDAC. 

PMID- 25986718
TI  - Genetics: Insights into RA pathogenesis from DNA methylome analysis.

PMID- 25986719
TI  - Experimental arthritis: Antiviral IFN-lambda2 has unexpected roles in
      inflammation.

PMID- 25986717
TI  - Coeliac disease and rheumatoid arthritis: similar mechanisms, different antigens.
AB  - Rheumatoid arthritis (RA) and coeliac disease are inflammatory diseases that both
      have a strong association with class II HLAs: individuals carrying HLA-DQ2.5
      and/or HLA-DQ8 alleles have an increased risk of developing coeliac disease,
      whereas those carrying HLA-DR shared epitope alleles exhibit an increased risk of
      developing RA. Although the molecular basis of the association with specific HLA
      molecules in RA remains poorly defined, an immune response against post
      translationally modified protein antigens is a hallmark of each disease. In RA,
      understanding of the pathogenetic role of B-cell responses to citrullinated
      antigens, including vimentin, fibrinogen and alpha-enolase, is rapidly growing.
      Moreover, insight into the role of HLAs in the pathogenesis of coeliac disease
      has been considerably advanced by the identification of T-cell responses to
      deamidated gluten antigens presented in conjunction with predisposing HLA-DQ2.5
      molecules. This article briefly reviews these advances and draws parallels
      between the immune mechanisms leading to RA and coeliac disease, which point to a
      crucial role for T-cell-B-cell cooperation in the development of full-blown
      disease. Finally, the ways in which these novel insights are being exploited
      therapeutically to re-establish tolerance in patients with RA and coeliac disease
      are described. 

PMID- 25986720
TI  - Clinical development of siltuximab.
AB  - Siltuximab is a chimeric monoclonal antibody targeting interleukin-6 (IL-6),
      which in the fall of 2014 became the first FDA-approved treatment of the rare
      disease idiopathic multicentric Castleman's disease (MCD). MCD is a non-clonal
      lymphoproliferative disorder in which common symptoms include fever, night
      sweats, weight loss, and fatigue. Symptoms are driven by an overall
      hypercytokinemia, predominantly IL-6. While under clinical development,
      siltuximab was studied in several other disease states including multiple
      myeloma, non-Hodgkin lymphomas, and several solid tumors in which it did not
      demonstrate significant benefit. The efficacy of siltuximab in MCD is mainly
      confined to systemic symptomatic response and quality of life benefits with
      minimal complete responses and approximately 30 % partial responses, by
      radiographic criteria. Siltuximab treatment therefore is important in the overall
      treatment of this rare disease state. This review focuses on the clinical
      development and pharmaceutical approval of siltuximab.

PMID- 25986721
TI  - Integrating oncogeriatric tools into the management of chronic lymphocytic
      leukemia: current state of the art and challenges for the future.
AB  - Although the achievement of deep and long lasting remissions is a realistic goal
      of therapy in the fit patient with chronic lymphocytic leukemia (CLL), this
      disease typically affects elderly patients who also show one or more concomitant
      pathological conditions or functional limitations that have an additive effects
      on the reduction of patient's life expectancy and represent major limitations in
      the adoption of standard therapies. In these unfit but typical patients with CLL,
      the goals of treatment may vary from achieving good remissions without severe
      toxicity to simple palliation. Differently from the past when the definition of
      patient medical status was mainly based on age and was left to the subjective
      assessment of the physician, today there are several tools to define in a
      standardized, reproducible, and multidimensional way the initial patient
      assessment and to plan treatment goals in an objective way. In this review, an
      overview of the current approaches to the definition of the medical fitness of
      the patient is provided along with some practical suggestions to integrate these
      tools in the clinical approach to elderly patients with CLL. 

PMID- 25986723
TI  - Microporous Metal-Organic Framework Based on a Bifunctional Linker for Selective
      Sorption of CO2 over N2 and CH4.
AB  - A bifunctional organic linker 4-(4-carboxyphenyl)-1,2,4-triazole (HCPT),
      incorporating both carboxylate and triazole groups, has been successfully used in
      the construction of a 2-fold interpenetrated dynamic metal-organic framework
      (MOF), {[Cu3(CPT)4(MU3-OH)].NO3.7H2O.EtOH}n (1) based on a triangular Cu(II)
      hydroxo cluster as secondary building unit (SBU). Upon solvation/desolvation and
      temperature, the crystal cell parameters of 1 could be fine-tuned. More
      importantly, a transformation from disordered phase to a more ordered phase after
      activation was observed via a single-crystal-to-single-crystal mode. Gas sorption
      studies reveal that the activated 1 exhibits highly selective sorption of CO2
      over N2 and CH4 at room temperature. 

PMID- 25986722
TI  - Novel immunologic approaches in lymphoma: unleashing the brakes on the immune
      system.
AB  - Immunotherapy is a promising therapeutic strategy in the treatment of lymphoma.
      The programmed death-1 (PD-1)/PD-ligand immune checkpoint pathway has been
      manipulated by tumor cells and serves as a mechanism of tumor evasion from the
      anti-tumor immune response. The recent development of anti-PD-1 antibodies has
      offered a therapeutic strategy for restoring the function of exhausted antigen
      specific T cells and enhancing the endogenous anti-tumor immunity. We review the
      clinical studies demonstrating efficacy and safety of PD-1 antibodies in
      relapsed/refractory Hodgkin, follicular, and diffuse large B cell lymphoma.
      Principles learned in the development of immune checkpoint blockade provide the
      foundation for immunotherapy under clinical investigation. 

PMID- 25986725
TI  - A multi-component polyoxometalate and its catalytic performance for CO2
      cycloaddition reactions.
AB  - A multi-component polyoxometalate based on earth-abundant elements
      (NH4)10[Co8(H2O)10V10Mo23O104(OH)6].34.5H2O () has been successfully obtained and
      characterized. Furthermore, compound acted as a Lewis acid catalyst and promoted
      the conversion of carbon dioxide to a cyclic carbonate under mild reaction
      conditions. 

PMID- 25986724
TI  - Older people going online: its value and before-after evaluation of volunteer
      support.
AB  - BACKGROUND: Although Internet usage can benefit older people by reducing social
      isolation, increasing access to services, and improving health and well-being,
      only a minority are online. Barriers to Internet uptake include attitude and a
      lack of knowledge and help. We have evaluated volunteer support in helping older
      people go online. Knowing what value the Internet has been to older people who
      have just gone online should guide how it is "sold" to those remaining offline.
      OBJECTIVE: Objectives of this study are (1) to assess the feasibility of
      recruiting volunteers aged 50 years and older and supporting them in helping
      people (ie, beneficiaries) aged 65 years and older go online, (2) to assess the
      impact of beneficiaries using the Internet on contacts with others, loneliness,
      and mental health, and (3) to assess the perceived value to beneficiaries of
      going online. METHODS: Beneficiaries received help in using the Internet from 32
      volunteers in one of two ways: (1) one-on-one in their own homes, receiving an
      average of 12 hours of help over eight visits, or (2) in small group sessions,
      receiving 12 hours of help over six visits. We assessed, at registration and
      follow-up, the number of contacts with others, using Lubben's 6-item Lubben
      Social Network Scale (LBNS-6), loneliness, using De Jong Gierveld's 6-item De
      Jong Gierveld loneliness scale (DJG-6), and mental well-being, using Tennant's
      Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS). We also assessed how
      beneficiaries valued going online using a Social Return on Investment (SROI)
      approach by postal survey. RESULTS: A total of 144 beneficiaries were recruited
      with the aim of helping them go online via one-on-one (n=58) or small group
      (n=86) sessions. Data through to follow-up were available on 76.4% (110/144) of
      participants. From baseline to follow-up, the number of contacts with others was
      significantly increased-LBNS-6, mean 13.7 to mean 17.6-loneliness scores were
      reduced-DJG-6, mean 2.38 to mean 1.80-and mental well-being improved-SWEMWBS,
      mean 24.06 to mean 24.96. Out of six options, beneficiaries valued better
      communication with family and friends most and better health care least as a
      benefit of using the Internet. Out of nine options, having the Internet was
      valued less than having TV, but more than, for example, having a weekly visit
      from a cleaner. There were no associations between values placed on Internet use
      or volunteer help and psychological improvements. CONCLUSIONS: Volunteer help to
      go online seemed to result in increased social contacts, reduced loneliness, and
      improved mental well-being and was valued quite highly by beneficiaries. Although
      the use of the Internet for health care was the least valued, improved social
      contact can improve health. Contacting family is likely to be the best "selling
      point" of the Internet for older people.

PMID- 25986726
TI  - The nicotinic acetylcholine receptor-mediated reciprocal effects of the tobacco
      nitrosamine NNK and SLURP-1 on human mammary epithelial cells.
AB  - Recent research has demonstrated that the nicotinergic signaling network of
      mammary epithelium can both mediate the physiological control of normal breast
      epithelial cells (BECs) and exhibit tumor-promoting effects on malignant BECs.
      Therefore, mammary nicotinic acetylcholine (ACh) receptors (nAChRs) may become a
      specific target for novel anti-breast cancer therapies. Toward this goal, we
      investigated the difference in the ACh receptor repertoires between normal and
      malignant BECs, determined effects of nicotinic ligands on 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanone (NNK)-dependent activation of ERK1/2 and tumorigenic
      transformation of MCF10A cells, and characterized reciprocal effects of NNK and
      SLURP (secreted mammalian Ly-6/urokinase plasminogen activator receptor related
      protein-1)-1 on the expression of nAChR subunits and several oncogenes and tumor
      suppressing genes in BECs. Both the non-malignant MCF10A and malignant MCF7
      breast cells expressed alpha3, alpha5, alpha7, alpha9, alpha10, beta1, beta2,
      gamma, delta and epsilon nAChR subunits and M(1), M(3), M(4) and M(5) muscarinic
      receptor subtypes. The malignancy was associated with expression of alpha1,
      alpha4 and beta4 nAChR subunits and M(2) subtype. Malignant transformation of
      BECs was also associated with overexpression of alpha7-, and alpha9-made nAChRs.
      NNK upregulated ERK1/2 phosphorylation, stimulated expression of the gene
      encoding the tumor-promoter HGF, downregulated expression of the tumor suppressor
      gene CDKN2A, and induced tumorigenic transformation of MCF10A cells. Compared to
      the canonical nAChR antagonists, SLURP-1 showed the highest ability to abolish
      the nAChR-mediated effects of NNK in both cell-signaling and cell-transformation
      assays and reversed many effects of NNK on gene expression. SLURP-1 also markedly
      upregulated the tumor suppressor genes CDKN2B, RUNX3 and TP73. Altogether, the
      obtained results provided new insight into the molecular mechanisms of nAChR
      mediated oncogenic effects of NNK on BECs and demonstrated the ability to abolish
      or reverse these effects by SLURP-1.

PMID- 25986727
TI  - Importance of sigma factor mutations in increased triclosan resistance in
      Salmonella Typhimurium.
AB  - BACKGROUND: Salmonella enterica is the second most common foodborne pathogen. The
      use of biocides is crucial to prevent spread of foodborne pathogens, and it would
      be devastating for food safety if Salmonella would become resistant to the
      disinfectants used. Another concern is that exposure to disinfectants might lead
      to decreased susceptibility to antibiotics. The current study aimed to identify
      genetic changes causing high level triclosan resistance in S. enterica serovar
      Typhimurium and evaluate how these affected antibiotic resistance and efflux pump
      activity. RESULTS: Wild type strains S. Typhimurium 4/74 and DTU3 were adapted to
      increasing concentrations of the biocide triclosan by serial passage. High level
      triclosan resistant isolates (MIC > 1000 MUg/ml) were obtained. Strains were
      genome sequenced, and SNPs in fabI, rpoS and rpoD were found to be associated
      with high level resistance. However, work with defined mutants revealed that a
      SNP in fabI was not sufficient to obtain high level resistance. This required
      additional mutations in the sigma factors rpoS or rpoD. The adapted strains
      showed triclosan-dependent increased efflux, increased fabI expression and
      reduced susceptibility towards the antibiotics enrofloxacin and
      sulphamethoxazole/trimethoprim. CONCLUSIONS: Medium level triclosan resistance
      could be obtained by fabI mutations in S. Typhimurium, however, high level
      resistance was found to require sigma factor mutations in addition to a fabI
      mutation. Reduced antibiotic sensitivity was observed for the adapted strains,
      which could be associated with increased efflux.

PMID- 25986728
TI  - N-acetyl-L-tryptophan delays disease onset and extends survival in an amyotrophic
      lateral sclerosis transgenic mouse model.
AB  - BACKGROUND: Whether L-NAT, a cytochrome c release inhibitor and an antagonist of
      NK-1R, provides protection in ALS is not known. RESULTS: L-NAT delays disease
      onset and mortality in mSOD1(G93A) ALS mice by inhibiting mitochondrial cell
      death pathways, inflammation, and NK-1R downregulation. CONCLUSION: L-NAT offers
      protection in a mouse model of ALS. SIGNIFICANCE: Data suggest the potential of L
      NAT as a novel therapeutic strategy for ALS and provide insight into its action
      mechanisms. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      characterized by progressive motor neuron loss, while inflammation has been
      implicated in its pathogenesis. Both inhibitors of cytochrome c release and
      antagonists of the neurokinin 1 receptor (NK-1R) have been reported to provide
      neuroprotection in ALS and/or other neurodegenerative diseases by us and other
      researchers. However, whether N-acetyl-L-tryptophan (L-NAT), an inhibitor of
      cytochrome c release and an antagonist of NK-1R, provides neuroprotection in ALS
      remains unknown. Here we demonstrate that the administration of L-NAT delayed
      disease onset, extended survival, and ameliorated deteriorations in motor
      performance in mSOD1(G93A) ALS transgenic mice. Our data showed that L-NAT
      reached the spinal cord, skeletal muscle, and brain. In addition, we demonstrate
      that L-NAT reduced the release of cytochrome c/smac/AIF, increased Bcl-xL levels,
      and inhibited the activation of caspase-3. L-NAT also ameliorated motor neuron
      loss and gross atrophy, and suppressed inflammation, as shown by decreased GFAP
      and Iba1 levels. Furthermore, we found gradually reduced NK-1R levels in the
      spinal cords of mSOD1(G93A) mice, while L-NAT treatment restored NK-1R levels. We
      propose the use of L-NAT as a potential therapeutic invention against ALS.

PMID- 25986729
TI  - Elevated microRNA-181c and microRNA-30d levels in the enlarged amygdala of the
      valproic acid rat model of autism.
AB  - Autism spectrum disorders are severe neurodevelopmental disorders, marked by
      impairments in reciprocal social interaction, delays in early language and
      communication, and the presence of restrictive, repetitive and stereotyped
      behaviors. Accumulating evidence suggests that dysfunction of the amygdala may be
      partially responsible for the impairment of social behavior that is a hallmark
      feature of ASD. Our studies suggest that a valproic acid (VPA) rat model of ASD
      exhibits an enlargement of the amygdala as compared to controls rats, similar to
      that observed in adolescent ASD individuals. Since recent research suggests that
      altered neuronal development and morphology, as seen in ASD, may result from a
      common post-transcriptional process that is under tight regulation by microRNAs
      (miRs), we examined genome-wide transcriptomics expression in the amygdala of
      rats prenatally exposed to VPA, and detected elevated miR-181c and miR-30d
      expression levels as well as dysregulated expression of their cognate mRNA
      targets encoding proteins involved in neuronal system development. Furthermore,
      selective suppression of miR-181c function attenuates neurite outgrowth and
      branching, and results in reduced synaptic density in primary amygdalar neurons
      in vitro. Collectively, these results implicate the small non-coding miR-181c in
      neuronal morphology, and provide a framework of understanding how dysregulation
      of a neurodevelopmentally relevant miR in the amygdala may contribute to the
      pathophysiology of ASD. 

PMID- 25986730
TI  - Are associations between electronic media use and BMI different across levels of
      physical activity?
AB  - BACKGROUND: The use of electronic media has been found to be a risk factor for
      higher BMI and for being overweight. Physical activity has been found to be
      associated with lower BMI and lower risk for being overweight. Little is known
      about whether the associations between physical activity and electronic media use
      are additive or interactive in predicting BMI and risk for overweight among
      adolescents. METHODS: The data used in this study stem from the 2009/2010 survey
      of "Health Behaviour in School-aged Children (HBSC) study: A WHO Cross-National
      Survey. The sample consisted of 107184 13 and 15 year students from 30 different
      countries. Multilevel regression models were used to produce the presented
      estimates. RESULTS: Overall, 18% of boys and 11% of girls were classified as
      overweight. EM use was found to be associated with increased BMI z-scores and
      odds for overweight among both boys and girls who did not comply with physical
      activity guidelines. Among physically active adolescents, EM was found to be
      significantly associated with BMI or odds for overweight among girls, but not
      among boys. CONCLUSION: While the usage of EM appear to be inconsequential for
      BMI and the risk of overweight among physically active boys, we find evidence
      indicating that EM use is associated with BMI and risk for overweight among
      girls, including those who report complying with MVPA guidelines.

PMID- 25986731
TI  - Ethanol attenuates peripheral NMDAR-mediated vascular oxidative stress and
      pressor response.
AB  - There are no studies on the acute effect of ethanol on peripheral N-methyl-d
      aspartate receptor (NMDAR)-mediated increases in reactive oxygen species (ROS)
      and blood pressure (BP). We tested the hypothesis that ethanol antagonism of
      peripheral NMDAR dampens systemic NMDA-evoked increases in vascular ROS and BP.
      We investigated the effect of ethanol (1 g/kg) on BP and heart rate (HR)
      responses elicited by systemic bolus (125-1000 MUg/kg, intra-venous [i.v.]) or
      infused (180 MUg/kg/min) NMDA in conscious male Sprague-Dawley rats. We also
      hypothesized that peripheral NMDAR blockade with DL-2-Amino-5-phosphonopentanoic
      acid (AP-5; 5 mg/kg, i.v.) uncovers an ethanol- (1 or 1.5 g/kg) evoked
      hypotensive response. Ethanol attenuated the peripheral NMDAR-mediated pressor
      and bradycardic responses caused by NMDA infusion, and ex vivo studies revealed
      parallel ethanol attenuation of peripheral NMDAR-mediated increases in vascular
      ROS. While ethanol (1 or 1.5 g/kg) alone had no effect on BP, the higher dose
      caused a hypotensive response in the presence of NMDAR blockade (AP-5). Blood
      ethanol concentrations were not statistically different in the groups that
      received ethanol alone or along with NMDA or AP-5. These findings are the first
      to demonstrate ethanol attenuation of peripheral NMDAR-mediated pressor response,
      and the uncovering of ethanol-evoked hypotension in the presence of peripheral
      NMDAR blockade. 

PMID- 25986733
TI  - Longitudinal assessment of immuno-metabolic parameters in multiple sclerosis
      patients during treatment with glatiramer acetate.
AB  - OBJECTIVE: We investigated the effect of glatiramer acetate (GA) on the
      modulation of immune cell subpopulations and serum levels of multiple
      immune/metabolic markers in patients with relapsing-remitting multiple sclerosis
      (RRMS) to understand whether the treatment with GA could induce a specific change
      in the immunometabolic asset of patients with RRMS. MATERIAL AND METHODS: We
      performed an extensive peripheral blood immunophenotyping and measured serum
      levels of several parameters involved in the pathogenesis of RRMS and also
      relevant in the pathogenesis of metabolic syndrome and obesity such as leptin,
      soluble leptin-receptor (sLep-R), myeloperoxidase (MPO), soluble CD40 ligand
      (sCD40-L), soluble tumor necrosis factor-receptor (sTNF-R), monocyte
      chemoattractant protein 1 (MCP-1), soluble Inter-Cellular Adhesion Molecule-1
      (sICAM-1) and osteoprotegerin (OPG), in 20 naive-to-treatment RRMS patients and
      20 healthy controls. We repeated these analyses over time at 6 and 12 months
      after starting GA treatment. RESULTS: Our analysis showed that naive-to-treatment
      RRMS patients had a lower number of CD16(+)CD56(+) NK cells, CD19(+) B cells,
      CD4(+) T cells co-expressing the MHC class II activation marker HLA-DR
      (CD4(+)DR(+)) and naive CD4(+)CD45RA(+) T cells in basal conditions. GA treatment
      induced a specific and significant decrease of circulating CD19(+) B cells. Naive
      to-treatment RRMS patients also showed a significantly higher number of CD4(+) T
      cells with a memory phenotype (CD4(+)CD45RO(+)) whose peripheral frequency was
      not affected by GA treatment. These changes over time associated with a higher
      serum concentration of leptin and lower levels of MPO. GA treatment also reduced
      significantly the circulating levels of sCD40-L and sTNF-R overtime. CONCLUSIONS:
      Our data suggest that the clinical outcome of GA treatment is associated with
      changes in immune cell subpopulations and modulation of specific immunometabolic
      markers. These data add substantial evidence of the immune modulating effect of
      GA during RRMS and could be of relevance in understanding the pathogenesis of
      disease and its follow-up.

PMID- 25986736
TI  - Successful acquisition of a neutralizing monoclonal antibody against a novel
      neutrophil-activating peptide, mitocryptide-1.
AB  - Mitocryptide-1 (MCT-1) is a novel neutrophil-activating peptide derived from
      mitochondrial cytochrome c oxidase subunit VIII, and its physiological role and
      involvement in various diseases have not yet been elucidated. Generating
      neutralizing antibodies against the function of MCT-1 is of particular importance
      for investigating its physiological and pathophysiological roles, because MCT-1
      is a fragmented peptide of its mother protein and hence it is very difficult to
      manipulate its expression level genetically without affecting expression of the
      mother protein. Here, we report the successful generation of a neutralizing
      monoclonal antibody (MAb) against MCT-1. This MAb, designated NM1B1, which
      specifically bound to the region of positions 9-22 of MCT-1, showed concentration
      dependent inhibition of MCT-1-induced migration and beta-hexosaminidase release
      in neutrophilic/granulocytic differentiated HL-60 cells. Thus, NM1B1, as a
      neutralizing MAb against MCT-1, could elucidate not just the physiological
      regulatory mechanisms of MCT-1 but also its pathophysiological involvement in
      various inflammatory diseases in vivo. 

PMID- 25986735
TI  - Circulating miR-126 is a potential biomarker to predict the onset of type 2
      diabetes mellitus in susceptible individuals.
AB  - Type 2 diabetes mellitus (T2DM) is a major public health problem in China.
      Diagnostic markers are urgently needed to identify individuals at risk of
      developing T2DM and thus encouraging healthier life styles. Circulating miRNAs
      are valuable sources for non-invasive biomarkers of various diseases. The aim of
      this study was to examine whether reduced miR-126 expression could predict the
      onset of T2DM in susceptible individuals. Two groups of study subjects were
      involved, one group was diagnosed T2DM in 2013 and the other group was healthy
      control. To this end, our results showed that miR-126 expression were already
      decreased before the manifestation of T2DM. Univariable logistic regression
      confirmed that the plasma miR-126 level was inversely associated with the onset
      of DM (P = 0.0158 ? 0.05), suggesting reduced miR-126 is a predictor for the
      onset of T2DM. According to the logistic regression model and ROC curve, a cut
      off points of miR-126 plasma level as 35 is recommended for clinical study to
      predict whether an individual is more likely to develop T2DM. If miR-126
      expression is lower than 35, the individual is more likely to T2DM in the next 2
      years. In conclusion, our results support the notion that the circulating miR-126
      can be developed into a non-invasive and rapid diagnostic tool for the prediction
      of susceptible individuals to developing T2DM. 

PMID- 25986737
TI  - Biochemical characterization of a heterotrimeric G(i)-protein activator peptide
      designed from the junction between the intracellular third loop and sixth
      transmembrane helix in the m4 muscarinic acetylcholine receptor.
AB  - Muscarinic acetylcholine receptors (mAChRs) are G-protein coupled receptors
      (GPCRs) that are activated by acetylcholine released from parasympathetic nerves.
      The mAChR family comprises 5 subtypes, m1-m5, each of which has a different
      coupling selectivity for heterotrimeric GTP-binding proteins (G-proteins). m4
      mAChR specifically activates the Gi/o family by enhancing the guanine nucleotide
      exchange factor (GEF) reaction with the Galpha subunit through an interaction
      that occurs via intracellular segments. Here, we report that the m4 mAChR mimetic
      peptide m4i3c(14)Gly, comprising 14 residues in the junction between the
      intracellular third loop (i3c) and transmembrane helix VI (TM-VI) extended with a
      C-terminal glycine residue, presents GEF activity toward the Gi1 alpha subunit
      (Galphai1). The m4i3c(14)Gly forms a stable complex with guanine nucleotide-free
      Galphai1 via three residues in the VTI(L/F) motif, which is conserved within the
      m2/4 mAChRs. These results suggest that this m4 mAChR mimetic peptide, which
      comprises the amino acid of the mAChR intracellular segments, is a useful tool
      for understanding the interaction between GPCRs and G-proteins. 

PMID- 25986734
TI  - The influence of neighborhood socioeconomic status and race on survival from
      ovarian cancer: a population-based analysis of Cook County, Illinois.
AB  - PURPOSE: Despite significant improvements in treatment for ovarian cancer,
      survival is poorer for non-Hispanic black (NHB) women compared to non-Hispanic
      white (NHW) women. Neighborhood socioeconomic status (SES) has been implicated in
      racial disparities across a variety of health outcomes and may similarly
      contribute to racial disparities in ovarian cancer survival. The purpose of this
      analysis is to assess the influence of neighborhood SES on NHB-NHW survival
      differences after accounting for differences in tumor characteristics and in
      treatment. METHODS: Data were obtained from 2432 women (443 NHB and 1989 NHW)
      diagnosed with epithelial ovarian cancer in Cook County, Illinois between 1998
      and 2007. Neighborhood (i.e., census tract) SES at the time of diagnosis was
      calculated for each woman using two well-established composite measures of
      affluence and disadvantage. Cox proportional hazard models measured the
      association between NHB race and survival after adjusting for age, tumor
      characteristics, treatment, year of diagnosis, and neighborhood SES. RESULTS:
      There was a strong association between ovarian cancer survival and both measures
      of neighborhood SES (P < .0001 for both affluence and disadvantage). After
      adjusting for age, tumor characteristics, treatment, and year of diagnosis, NHB
      were more likely than NHW to die of ovarian cancer (hazard ratio [HR] = 1.47, 95%
      confidence interval [CI]: 1.28-1.68). The inclusion of neighborhood affluence and
      disadvantage into models separately and together attenuated this risk
      (HRaffluence = 1.37, 95% CI: 1.18-1.58; HRdisadvantage = 1.28, 95% CI: 1.08-1.52;
      and HRaffluence + disadvantage = 1.28, 95% CI: 1.08-1.52. CONCLUSIONS:
      Neighborhood SES, as measured by composite measures of affluence and
      disadvantage, is a predictor of survival in women diagnosed with ovarian cancer
      in Cook County, Illinois and may contribute to the racial disparity in survival.

PMID- 25986738
TI  - Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial
      mesenchymal transition by regulating the PI3K-Akt-GSK-3beta signaling pathway.
AB  - Soluble epoxide hydrolase (sEH) plays an essential role in chronic kidney disease
      by hydrolyzing renoprotective epoxyeicosatrienoic acids to the corresponding
      inactive dihydroxyeicosatrienoic acids. However, there have been few mechanistic
      studies elucidating the role of sEH in epithelial-mesenchymal transition (EMT).
      The present study investigated, in vitro and in vivo, the role of sEH in
      proteinuria-induced renal tubular EMT and the underlying signaling pathway. We
      report that urinary protein (UP) induced EMT in cultured NRK-52E cells, as
      evidenced by decreased E-cadherin expression, increased alpha-smooth muscle actin
      (alpha-SMA) expression, and the morphological conversion to a myofibroblast-like
      phenotype. UP incubation also resulted in upregulated sEH, activated
      phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/Akt) signaling and
      increased phosphorylated glycogen synthase kinase-3beta (GSK-3beta). The PI3K
      inhibitor LY-294002 inhibited phosphorylation of Akt and GSK-3beta as well as
      blocking EMT. Importantly, pharmacological inhibition of sEH with 12-(3-adamantan
      1-yl- ureido)-dodecanoic acid (AUDA) markedly suppressed PI3K-Akt activation and
      GSK-3beta phosphorylation. EMT associated E-cadherin suppression, alpha-SMA
      elevation and phenotypic transition were also attenuated by AUDA. Furthermore, in
      rats with chronic proteinuric renal disease, AUDA treatment inhibited PI3K-Akt
      activation and GSK-3beta phosphorylation, while attenuating levels of EMT
      markers. Overall, our findings suggest that sEH inhibition ameliorates
      proteinuria-induced renal tubular EMT by regulating the PI3K-Akt-GSK-3beta
      signaling pathway. Targeting sEH might be a potential strategy for the treatment
      of EMT and renal fibrosis. 

PMID- 25986739
TI  - [FGF/FGFR signalling: Implication in oncogenesis and perspectives].
AB  - Deregulation of FGF (fibroblast growth factor)/FGFR (fibroblast growth factor
      receptor) signalling leads to the promotion of several oncogenic mechanisms:
      proliferation, epithelial-mesenchymal transition, cytoskeleton modifications,
      migration and angiogenesis. Deregulation of this pathway is reported in various
      cancers at early stages, and can therefore be responsible for the emergence of
      the hallmarks of cancer. It is necessary to precise downstream pathways of FGFR
      signalling to understand its oncogenic potential. We will then describe its
      implications in different cancer types. Oncogenic mechanisms will be studied
      through the example of melanoma, in which deregulation of FGF/FGFR pathway is
      considered as a driver event and occurs in nearly 90% of cases. The FGF/FGFR
      signalling pathway is a putative therapeutic target. Numerous agents are in
      active development, operating through a selective or multi-targeted approach.
      Recent studies have shown rather disappointing results in non-selected patients,
      but promising results in patients with FGF/FGFR pathway alterations. A careful
      screening of patients is the key to a valuable evaluation of these new targeted
      molecular therapies. 

PMID- 25986740
TI  - [Innovative therapies for metastatic melanoma in elderly patients].
AB  - The mortality rate for malignant melanoma is higher in elderly patients aged 75
      years or more, with over 25% of melanomas being diagnosed in this population.
      This poorer prognosis might perhaps be improved by emerging targeted therapies
      and immunotherapy, although these agents must be prescribed with care in this
      rather fragile population. The purpose of our review of the literature concerning
      phase-2 and -3 published trials of these innovative molecules was to examine
      their optimal use in elderly patients presenting metastatic malignant melanoma.
      Most of the trials examined included elderly patients and some were analyzed by
      age sub-groups. In conclusion, elderly patients with ECOG 0/1 status can be given
      ipilimumab or vemurafenib as first-line therapy depending on tumoral BRaf
      mutation status. The benefit of combined targeted therapies does not seem to
      apply consistently in elderly patients and their use must be discussed. Further
      specific data must be collected in elderly patients concerning anti-PD1
      molecules. For more fragile patients, risk scales or scores should enable more
      accurate use of innovative therapies in metastatic melanoma. Moreover, physicians
      must be aware of the common drug interactions with targeted therapies, since
      elderly patients are often taking several concomitant drugs.

PMID- 25986741
TI  - Olfactory function combined with morphology distinguishes Parkinson's disease.
AB  - OBJECTIVE: This study aimed to examine whether the volume of the olfactory bulbs
      and tracts (OB & T) on magnetic resonance imaging (MRI) is useful for
      differentiating Parkinson's disease (PD) from PD-related disorders. METHODS: The
      study group comprised 13 patients with PD, 11 with multiple system atrophy (MSA),
      five with progressive supranuclear palsy, and five with corticobasal degeneration
      (PSP/CBD). All patients were evaluated using the odor stick identification test
      for Japanese (OSIT-J), (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy, and
      brain MRI. OB & T areas on 1-mm-thick coronal images were measured and summed for
      volumes. We examined relationships between olfactory function and volume, and
      cardiovascular dysautonomia. We defined the cut-off values for OSIT-J score or
      MIBG uptake and OB & T volume to discriminate PD from PD-related disorders and
      calculated the proportional rate of PD in four categorized groups. RESULTS: OB &
      T volume was smaller in PD than in MSA or PSP/CBD (p < 0.05 each). The cut-off
      for detecting PD patients was OSIT-J score <8, heart/mediastinum ratio <1.6, and
      OB & T volume <270 mm(3). In the group with OSIT-J score <8 and OB & T volume
      <270 mm(3), the proportion of PD patients among all patients with PD-related
      disorders was 91%. The rate of probable PD gradually increased as OSIT-J score
      and OB & T volume decreased (p < 0.001). CONCLUSIONS: Although preliminary, these
      data obtained from a combined morphological and functional evaluation of OB or
      cardiovascular dysautonomia could be useful for further differential of PD and
      other PD-related disorders.

PMID- 25986742
TI  - Parkinson bradykinesia correlates with EEG background frequency and perceptual
      forward projection.
AB  - BACKGROUND: To deal with processing-time in the nervous system, visuomotor
      control requires anticipation. An index for such anticipation is provided by the
      'flash-lag illusion' in which moving objects are perceived ahead of static
      objects while actually being in the same place. We investigated the
      neurophysiological relation between visuomotor anticipation and motor velocity in
      Parkinson's disease (PD) and controls. METHODS: Motor velocity was assessed by
      the number of keystrokes in 30s ('kinesia score') and visuomotor anticipation in
      a behavioural flash-lag paradigm while electroencephalography data was obtained.
      PD patients (n = 24) were divided in a 'PDslow' and a 'PDfast' group based on
      kinesia score. RESULTS: The PDslow group had a lower kinesia score than controls
      (resp. 40.3 +/- 1.7 and 64.9 +/- 4.6, p < 0.001). The flash-lag illusion was
      weaker in the PDslow group than in controls (resp. fractions 0.32 +/- 0.04 and
      0.50 +/- 0.09 of the responses indicating perceived lagging, p = 0.03).
      Furthermore, the magnitude of the flash-lag illusion correlated with the kinesia
      score (cc = 0.45, p = 0.02). Finally, electroencephalography background frequency
      was lower in the PDslow group than in controls (resp 8.24 +/- 0.24 and 9.1 +/-
      0.32 Hz, p = 0.01) and background frequency correlated with the kinesia score (cc
      = 0.58, p = 0.001). CONCLUSIONS: The decreased flash-lag illusion and lower
      electroencephalography background frequency in more bradykinetic PD patients
      provides support for disturbed visuomotor anticipations, putatively caused by
      reduced, sub-cortically mediated, network efficiency. This suggests a link
      between anticipation in early-stage visual motion processing and motor
      preparation.

PMID- 25986743
TI  - A computational approach to persistence, permanence, and endotacticity of
      biochemical reaction systems.
AB  - We introduce a mixed-integer linear programming (MILP) framework capable of
      determining whether a chemical reaction network possesses the property of being
      endotactic or strongly endotactic. The network property of being strongly
      endotactic is known to lead to persistence and permanence of chemical species
      under genetic kinetic assumptions, while the same result is conjectured but as
      yet unproved for general endotactic networks. The algorithms we present are the
      first capable of verifying endotacticity of chemical reaction networks for
      systems with greater than two constituent species. We implement the algorithms in
      the open-source online package CoNtRol and apply them to a large sample of
      networks from the European Bioinformatics Institute's BioModels Database. We use
      strong endotacticity to establish for the first time the permanence of a well
      studied circadian clock mechanism. 

PMID- 25986744
TI  - Activation of mucosal mast cells promotes inflammation-related colon cancer
      development through recruiting and modulating inflammatory CD11b(+)Gr1(+) cells.
AB  - Mast cells (MCs) have been reported to be one of the important immunoregulatory
      cells in promoting the development of colitis-related colon cancer (CRC). It is
      not clear which MC subtypes play critical roles in CRC progression from colitis
      to cancer because mucosal mast cells (MMCs) are distinct from connective tissue
      mast cells (CTMCs) in maintaining intestinal barrier function under homeostatic
      and inflammatory conditions. In the current study, we found that MMC numbers and
      the gene expressions of MMC-specific proteases increased significantly in an
      induced CRC murine model. The production of mast cell protease-1 (mMCP-1) after
      MMC activation not only resulted in the accumulation of CD11b(+)Gr1(+)
      inflammatory cells in the colon tissues but also modulated the activities of
      CD11b(+)Gr1(+) cells to support tumor cell growth and to inhibit T cell
      activation. Blocking the MMC activity in mice that had developed colitis-related
      epithelium dysplasia, CD11b(+)Gr1(+) infiltration was reduced and CRC development
      was inhibited. Our results suggest that MMC activation recruited and modulated
      the CD11b(+)Gr1(+) cells to promote CRC and that MMCs can be potential
      therapeutic targets for the prevention of CRC development. 

PMID- 25986745
TI  - Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the
      'future' in dermatology therapeutics?
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      and comprise three different isoforms namely PPARalpha, PPARgamma, and
      PPARbeta/delta with PPARbeta/delta being the predominant subtype in human
      keratinocytes. After binding with specific ligands, PPARs regulate gene
      expression, cell growth and differentiation, apoptosis, inflammatory responses,
      and tumorogenesis. PPARs also modulate a wide variety of skin functions including
      keratinocyte proliferation, epidermal barrier formation, wound healing,
      melanocyte proliferation, and sebum production. Recent studies have shown the
      importance of PPARs in the pathogenesis of many dermatological disorders.
      Clinical trials have suggested possible role of PPAR agonists in the management
      of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and
      lipodystrophy to cutaneous malignancies including melanoma. This article is
      intended to be a primer for dermatologists in their understanding of clinical
      relevance of PPARs and PPAR agonists in dermatology therapeutics. 

PMID- 25986747
TI  - Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism.
AB  - Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of
      autism spectrum disorder (ASD). Tremendous progress in understanding the
      pathogenesis of TSC has been made in recent years, along with initial trials of
      medical treatment aimed specifically at the underlying mechanism of the disorder.
      At the cellular level, loss of TSC1 or TSC2 results in upregulation of the
      mechanistic target of rapamycin (mTOR) pathway. At the circuitry level, TSC and
      mTOR play crucial roles in axonal, dendritic, and synaptic development and
      function. In this review, we discuss the molecular mechanism underlying TSC, and
      how this disease results in aberrant neural connectivity at multiple levels in
      the central nervous system, leading to ASD symptoms. We then review recent
      advances in mechanism-based treatments of TSC, and the promise that these
      treatments provide for future mechanism-based treatment of ASD. Because of these
      recent advances, TSC represents an ideal model for how to make progress in
      understanding and treating the mechanisms that underlie ASD in general. 

PMID- 25986749
TI  - Modifying the Cold Gelation Properties of Quinoa Protein Isolate: Influence of
      Heat-Denaturation pH in the Alkaline Range.
AB  - Heat-denaturation of quinoa protein isolate (QPI) at alkali pH and its influence
      on the physicochemical and cold gelation properties was investigated. Heating QPI
      at pH 8.5 led to increased surface hydrophobicity and decreases in free and bound
      sulfhydryl group contents. Heating at pH 10.5 caused a lesser degree of changes
      in sulfhydryl groups and surface hydrophobicity, and the resulting solutions
      showed drastically increased solubility. SDS PAGE revealed the presence of large
      aggregates only in the sample heated at pH 8.5, suggesting that any aggregates
      present in the sample heated at pH 10.5 were non-covalently bound and
      disintegrated in the presence of SDS. Reducing conditions partially dissolved the
      aggregates in the pH 8.5 heated sample indicating the occurrence of disulphide
      bonding, but caused no major alterations in the separation pattern of the pH 10.5
      heated sample. Denaturation pH influenced the cold gelation properties greatly.
      Solutions heated at pH 8.5 formed a coarse coagulum with maximum G' of 5 Pa. Heat
      denaturation at 10.5 enabled the proteins to form a finer and regularly
      structured gel with a maximum G' of 1140 Pa. Particle size analysis showed that
      the pH 10.5 heated sample contained a higher level of very small particles (0.1-2
      MUm), and these readily aggregated into large particles (30-200 MUm) when pH was
      lowered to 5.5. Differences in the nature of aggregates formed during heating may
      explain the large variation in gelation properties.

PMID- 25986748
TI  - Antidepressant-like cognitive and behavioral effects of acute ketamine
      administration associated with plasticity in the ventral hippocampus to medial
      prefrontal cortex pathway.
AB  - RATIONALE: Acute low-dose administration of the N-methyl-D-aspartate (NMDA)
      receptor antagonist, ketamine, produces rapid and sustained antidepressant-like
      effects in humans and rodents. Recently, we found that the long-lasting effect of
      ketamine on the forced swim test requires ventral hippocampal (vHipp) activity at
      the time of drug administration. The medial prefrontal cortex (mPFC), a target of
      the vHipp dysregulated in depression, is important for cognitive flexibility and
      response strategy selection. Deficits in cognitive flexibility, the ability to
      modify thoughts and behaviors in response to changes in the environment, are
      associated with depression. We have shown that chronic stress impairs cognitive
      flexibility on the attentional set-shifting test (AST) and induces a shift from
      active to passive response strategies on the shock-probe defensive burying test
      (SPDB). OBJECTIVE: In this study, we tested the effects of ketamine on chronic
      stress-induced changes in cognitive flexibility and coping behavior on the AST
      and SPDB, respectively. Subsequently, we investigated vHipp-mPFC plasticity as a
      potential mechanism of ketamine's therapeutic action. RESULTS: Ketamine reversed
      deficits in cognitive flexibility and restored active coping behavior in
      chronically stressed rats. Further, high frequency stimulation in the vHipp
      replicated ketamine's antidepressant-like effects on the forced swim test and
      AST, but not on the SPDB. CONCLUSION: These results show that ketamine restores
      cognitive flexibility and coping response strategy compromised by stress.
      Activity in the vHipp-mPFC pathway may represent a neural substrate for some of
      the antidepressant-like behavioral effects of ketamine, including cognitive
      flexibility, but other circuits may mediate the effects of ketamine on coping
      response strategy.

PMID- 25986750
TI  - Uncorrelated multiway discriminant analysis for motor imagery EEG classification.
AB  - Motor imagery-based brain-computer interfaces (BCIs) training has been proved to
      be an effective communication system between human brain and external devices. A
      practical problem in BCI-based systems is how to correctly and efficiently
      identify and extract subject-specific features from the blurred scalp
      electroencephalography (EEG) and translate those features into device commands in
      order to control external devices. In real BCI-based applications, we usually
      define frequency bands and channels configuration that related to brain
      activities beforehand. However, a steady configuration usually loses effects due
      to individual variability among different subjects in practical applications. In
      this study, a robust tensor-based method is proposed for a multiway
      discriminative subspace extraction from tensor-represented EEG data, which
      performs well in motor imagery EEG classification without the prior
      neurophysiologic knowledge like channels configuration and active frequency
      bands. Motor imagery EEG patterns in spatial-spectral-temporal domain are
      detected directly from the multidimensional EEG, which may provide insights to
      the underlying cortical activity patterns. Extensive experiment comparisons have
      been performed on a benchmark dataset from the famous BCI competition III as well
      as self-acquired data from healthy subjects and stroke patients. The experimental
      results demonstrate the superior performance of the proposed method over the
      contemporary methods. 

PMID- 25986746
TI  - Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back.
AB  - Fragile X syndrome (FXS), an inherited intellectual disability often associated
      with autism, is caused by the loss of expression of the fragile X mental
      retardation protein. Tremendous progress in basic, preclinical, and translational
      clinical research has elucidated a variety of molecular-, cellular-, and system
      level defects in FXS. This has led to the development of several promising
      therapeutic strategies, some of which have been tested in larger-scale controlled
      clinical trials. Here, we will summarize recent advances in understanding
      molecular functions of fragile X mental retardation protein beyond the well-known
      role as an mRNA-binding protein, and will describe current developments and
      emerging limitations in the use of the FXS mouse model as a preclinical tool to
      identify therapeutic targets. We will review the results of recent clinical
      trials conducted in FXS that were based on some of the preclinical findings, and
      discuss how the observed outcomes and obstacles will inform future therapy
      development in FXS and other autism spectrum disorders. 

PMID- 25986751
TI  - Automated Seizure Onset Zone Approximation Based on Nonharmonic High-Frequency
      Oscillations in Human Interictal Intracranial EEGs.
AB  - A novel automated algorithm is proposed to approximate the seizure onset zone
      (SOZ), while providing reproducible output. The SOZ, a surrogate marker for the
      epileptogenic zone (EZ), was approximated from intracranial electroencephalograms
      (iEEG) of nine people with temporal lobe epilepsy (TLE), using three methods: (1)
      Total ripple length (TRL): Manually segmented high-frequency oscillations, (2)
      Rippleness (R): Area under the curve (AUC) of the autocorrelation functions
      envelope, and (3) Autoregressive model residual variation (ARR, novel algorithm):
      Time-variation of residuals from autoregressive models of iEEG windows. TRL, R,
      and ARR results were compared in terms of separability, using Kolmogorov-Smirnov
      tests, and performance, using receiver operating characteristic (ROC) curves, to
      the gold standard for SOZ delineation: visual observation of ictal video-iEEGs.
      TRL, R, and ARR can distinguish signals from iEEG channels located within the SOZ
      from those outside it (p < 0.01). The ROC AUC was 0.82 for ARR, while it was 0.79
      for TRL, and 0.64 for R. ARR outperforms TRL and R, and may be applied to
      identify channels in the SOZ automatically in interictal iEEGs of people with
      TLE. ARR, interpreted as evidence for nonharmonicity of high-frequency EEG
      components, could provide a new way to delineate the EZ, thus contributing to
      presurgical workup. 

PMID- 25986752
TI  - A Programmer-Interpreter Neural Network Architecture for Prefrontal Cognitive
      Control.
AB  - There is wide consensus that the prefrontal cortex (PFC) is able to exert
      cognitive control on behavior by biasing processing toward task-relevant
      information and by modulating response selection. This idea is typically framed
      in terms of top-down influences within a cortical control hierarchy, where
      prefrontal-basal ganglia loops gate multiple input-output channels, which in turn
      can activate or sequence motor primitives expressed in (pre-)motor cortices. Here
      we advance a new hypothesis, based on the notion of programmability and an
      interpreter-programmer computational scheme, on how the PFC can flexibly bias the
      selection of sensorimotor patterns depending on internal goal and task contexts.
      In this approach, multiple elementary behaviors representing motor primitives are
      expressed by a single multi-purpose neural network, which is seen as a reusable
      area of "recycled" neurons (interpreter). The PFC thus acts as a "programmer"
      that, without modifying the network connectivity, feeds the interpreter networks
      with specific input parameters encoding the programs (corresponding to network
      structures) to be interpreted by the (pre-)motor areas. Our architecture is
      validated in a standard test for executive function: the 1-2-AX task. Our results
      show that this computational framework provides a robust, scalable and flexible
      scheme that can be iterated at different hierarchical layers, supporting the
      realization of multiple goals. We discuss the plausibility of the "programmer
      interpreter" scheme to explain the functioning of prefrontal-(pre)motor cortical
      hierarchies. 

PMID- 25986753
TI  - Transcranial Magnetic Stimulation Combined with EEG Reveals Covert States of
      Elevated Excitability in the Human Epileptic Brain.
AB  - BACKGROUND: Transcranial magnetic stimulation combined with electroencephalogram
      (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In
      patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a
      stochastic occurrence despite constant stimulation parameters. This observation
      raises the possibility that the pre-stimulation period contains multiple covert
      states of brain excitability some of which are associated with the generation of
      EDs. OBJECTIVE: To investigate whether the interictal period contains "high
      excitability" states that upon brain stimulation produce EDs and can be
      differentiated from "low excitability" states producing normal appearing TMS-EEG
      responses. METHODS: In a cohort of 25 patients with Genetic Generalized
      Epilepsies (GGE) we identified two subjects characterized by the intermittent
      development of TMS-induced EDs. The high-excitability in the pre-stimulation
      period was assessed using multiple measures of univariate time series analysis.
      Measures providing optimal discrimination were identified by feature selection
      techniques. The "high excitability" states emerged in multiple loci (indicating
      diffuse cortical hyperexcitability) and were clearly differentiated on the basis
      of 14 measures from "low excitability" states (accuracy = 0.7). CONCLUSION: In
      GGE, the interictal period contains multiple, quasi-stable covert states of
      excitability a class of which is associated with the generation of TMS-induced
      EDs. The relevance of these findings to theoretical models of ictogenesis is
      discussed.

PMID- 25986754
TI  - Multifractal Analysis and Relevance Vector Machine-Based Automatic Seizure
      Detection in Intracranial EEG.
AB  - Automatic seizure detection technology is of great significance for long-term
      electroencephalogram (EEG) monitoring of epilepsy patients. The aim of this work
      is to develop a seizure detection system with high accuracy. The proposed system
      was mainly based on multifractal analysis, which describes the local singular
      behavior of fractal objects and characterizes the multifractal structure using a
      continuous spectrum. Compared with computing the single fractal dimension,
      multifractal analysis can provide a better description on the transient behavior
      of EEG fractal time series during the evolvement from interictal stage to
      seizures. Thus both interictal EEG and ictal EEG were analyzed by multifractal
      formalism and their differences in the multifractal features were used to
      distinguish the two class of EEG and detect seizures. In the proposed detection
      system, eight features (alpha0, alpha(min), alpha(max), Deltaalpha,
      f(alpha(min)), f(alpha(max)), Deltaf and R) were extracted from the multifractal
      spectrums of the preprocessed EEG to construct feature vectors. Subsequently,
      relevance vector machine (RVM) was applied for EEG patterns classification, and a
      series of post-processing operations were used to increase the accuracy and
      reduce false detections. Both epoch-based and event-based evaluation methods were
      performed to appraise the system's performance on the EEG recordings of 21
      patients in the Freiburg database. The epoch-based sensitivity of 92.94% and
      specificity of 97.47% were achieved, and the proposed system obtained a
      sensitivity of 92.06% with a false detection rate of 0.34/h in event-based
      performance assessment.

PMID- 25986755
TI  - Low functional programming of renal AT2R mediates the developmental origin of
      glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.
AB  - Our previous study has indicated that prenatal caffeine exposure (PCE) could
      induce intrauterine growth retardation (IUGR) of offspring. Recent research
      suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE
      could induce glomerulosclerosis and its underlying mechanisms remain unknown.
      This study aimed to demonstrate the induction to glomerulosclerosis in adult
      offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR
      was established by PCE, male fetuses and adult offspring at the age of postnatal
      week 24 were euthanized. The results revealed that the adult offspring kidneys in
      the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis,
      accompanied by elevated levels of serum creatinine and urine protein. Renal
      angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was
      reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R
      expression ratio was increased. The fetal kidneys in the PCE group displayed an
      enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced
      cortex width and an increase in the nephrogenic zone/cortical zone ratio.
      Observation by electronic microscope revealed structural damage of podocytes; the
      reduced expression level of podocyte marker genes, nephrin and podocin, was also
      detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys
      were inhibited by PCE, associated with the repression of the gene expression of
      glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c
      Ret) signaling pathway. These results demonstrated that PCE could induce
      dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and
      the low functional programming of renal AT2R might mediate the developmental
      origin of adult glomerulosclerosis. 

PMID- 25986756
TI  - Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity.
AB  - Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system
      toxin. To understand the molecular mechanisms of MC-induced reproductive system
      cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse
      Sertoli cells following MC-LR treatment. Our results revealed that the exposure
      to MC-LR resulted in an altered miRNA expression profile that might be
      responsible for the modulation of mRNA expression. Bio-functional analysis
      indicated that the altered genes were involved in specific cellular processes,
      including cell death and proliferation. Target gene analysis suggested that
      junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs
      through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively,
      these findings may enhance our understanding on the modes of action of MC-LR on
      mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity
      of MC-LR on the male reproductive system. 

PMID- 25986758
TI  - Kidney cancer: SWITCHing inconsequential.

PMID- 25986759
TI  - BPH: BPH6 results will lift the spirits of men with LUTS secondary to BOO.

PMID- 25986760
TI  - Corrigendum: BCG immunotherapy for bladder cancer--the effects of substrain
      differences.

PMID- 25986764
TI  - Prostate cancer: Intermediate risk: RT or ADT?

PMID- 25986766
TI  - [Hip arthroscopy after luxatio obturatoria. With contralateral unstable pelvic
      ring fracture].
AB  - Traumatic dislocation of the hip is a severe injury. Even in cases of an early
      uncomplicated repositioning there is a high risk of associated intra-articular
      injuries, such as lesions of the labrum, ruptures of the ligament of the head of
      the femur and loose bodies. The degree of damage caused by dislocation of the hip
      becomes apparent with a highly increased risk of developing postinjury
      osteoarthritis after dislocation of the hip. Some of the major intra-articular
      damage resulting from hip dislocation, e.g. loose bodies, can be detected by
      computed tomography and magnetic resonance imaging and can be effectively
      addressed by hip arthroscopy, thus aiming at reducing the acute symptoms and the
      risk of postinjury osteoarthritis. The force effect which causes dislocation of
      the hip can generate severe associated extra-articular injures as in the case
      described with an unstable fracture of the pelvis. This supplementary injury had
      to be considered while planning the operative therapy and rehabilitation. A
      patient presented after a traffic accident with a luxatio obturatoria on the
      right side and a complex fracture of the left pelvis including the posterior ring
      and the anterior wall of the acetabulum. After reposition of the right hip and
      operative therapy of the left side, a loose body was identified in the right hip
      joint during the computed tomography control of the osteosynthesis. Before
      patient mobilization extraction of the intra-articular loose body was performed
      arthroscopically. This was done in consideration of the reduced possibility of
      distraction due to the osteosynthesis on the contralateral side. Attention was
      particularly paid to the risk of intra-abdominal fluid extravasation (IAFE). This
      syndrome is described as a severe complication during hip arthoscopy especially
      in cases of defects of the hip capsule as assumed after hip dislocation and
      magnetic resonance imaging.

PMID- 25986767
TI  - [Sports injuries of the hand].

PMID- 25986768
TI  - [Complete rupture of the peroneal nerve by knee distortion].
AB  - This report describes a case of complete rupture of the peroneal nerve as a
      consequence of low velocity trauma. A 54-year-old physically fit patient suffered
      a complex trauma with complete nerve discontinuity as a result of knee joint
      distortion without external force. The initial medical findings were
      unremarkable, in particular neither the accident medical history nor the initial
      sensitivity impairment suggested the presence of serious knee damage; however,
      during clinical diagnostics a complex trauma with rupture of the peroneal nerve
      was found. Accordingly, an extensive revision with nerve suturing was carried
      out. 

PMID- 25986769
TI  - [Hand injuries in mountain sports].
AB  - BACKGROUND: Apart from clean cut finger amputations, every kind of hand injury
      can be seen in mountain and winter sports but only skier's thumb and injuries of
      the pulley system in sport climbers are seen in a greater number of cases.
      Nevertheless, these two common injuries as well as the rare frostbite of the
      fingers are often underdiagnosed or overdiagnosed as well as undertreated or
      overtreated. PURPOSE: This paper describes the diagnostics and treatment of
      skier's thumb, injuries of the pulley system in sport climbers and frostbite of
      the fingers. RESULTS: Before checking the metacarpophalangeal (MP) joint of the
      thumb for stability, radiographs should be taken to exclude a bony avulsion of
      the ulnar collateral ligament in skier's thumb. If there is no bony ligament
      avulsion further diagnostic procedures, e.g. ultrasound, are recommended to prove
      or exclude a Stener lesion, which is an absolute indication for operative
      treatment together with a dislocated bony ligament avulsion. To quantify the
      severity of a lesion of the pulley system ultrasound and magnetic resonance
      imaging (MRI) are needed. Most lesions of the pulley system can be treated
      conservatively. Only multiple pulley ruptures or isolated ruptures associated
      with a lesion of the lumbrical muscles or collateral ligaments require operative
      treatment. As long as there is no infection amputation should be done as late as
      possible in frostbite of the fingers because the extent of the frostbite can
      rarely be correctly estimated. CONCLUSION: Most cases of skier's thumb as well as
      lesions of the pulley system can be treated non-operatively but precise
      diagnostics are needed.

PMID- 25986770
TI  - [Proximal humeral fractures in the elderly : Quality of life, clinical results
      and institutionalization following primary reverse fracture arthroplasty].
AB  - BACKGROUND: Treatment of humeral head fractures in the elderly remains a
      challenge. Within the framework of demographic change the incidence as well as
      the direct and indirect consequences of injuries will rise. The analysis of an
      optimal treatment should include functional parameters as well as global health
      parameters, e.g. quality of life. OBJECTIVE: The aim of this study was the
      evaluation of functional outcome, institutionalization (necessity of placement in
      a residential care home for the elderly, even if temporary), the influence of
      cognitive deficits, quality of life and the pattern of complications after
      primary reverse shoulder arthroplasty. MATERIAL AND METHODS: The study included a
      total of 34 patients (mean age 79.8 +/- 6.7 years, 29 female) after implantation
      of a reversed modular fracture arthroplasty. The mean follow-up was 23 +/- 10.6
      months). The functional Constant-Murley score (CS), radiology results as well as
      the extent of institutionalization and quality of life as measured by the EQ-5D
      questionnaire were collated. RESULTS: The clinical examination showed good
      results in the CS (54 points, SD +/- 9). In comparison to the age and gender
      related CS according to Gerber the patient scores amounted to 78.9 %. The
      comparison of patients with and without cognitive deficits did not show any
      differences (53 vs. 54 points, p = 0.6525). The rate of institutionalization
      after treatment of humeral head fractures by reversed fracture arthroplasty was
      2.94 %. The quality of life measured with EQ-5D showed a health-related quality
      of life (HRQoL) of 0.801. The rate of complications was 2.94 % involving an
      incomplete lesion of the radial nerve which was in regression. CONCLUSION: The
      results of this study showed good to moderate functional results, very low rates
      of complications and institutionalization and very good results according to the
      HRQoL. In comparison to conservative treatment or plate osteosynthesis, better
      results were achieved in this study with respect to HRQoL.

PMID- 25986771
TI  - Reactive oxygen species in endothelial function - from disease to adaptation - .
AB  - Endothelial function is largely dictated by its ability to rapidly sense
      environmental cues and adapt to these stimuli through changes in vascular tone,
      inflammation/immune recruitment, and angiogenesis. When any one of these
      abilities is compromised, the endothelium becomes dysfunctional, which ultimately
      leads to disease. Reactive oxygen species (ROS) have been established at the
      forefront of endothelial dysfunction; however, more careful examination has
      demonstrated that ROS are fundamental to each of the sensing/signaling roles of
      the endothelium. The purpose of this review is to document endothelial ROS
      production in both disease and physiological adaptation. Through understanding
      new endothelial signaling paradigms, we will gain insight into more targeted
      therapeutic strategies for vascular diseases.

PMID- 25986772
TI  - Molecular simulations of mixed self-assembled monolayer coated gold nanoparticles
      in water.
AB  - Molecular dynamics simulations have been employed to study the hydration of a
      series of nanoparticles, each of which was coated with a mixed self-assembled
      monolayer (SAM) comprising methyl- and hydroxy-terminated alkane thiol chains.
      The mixing ratio of those chains are different for each nanoparticle. The
      simulations focused on the wetting behavior of the SAM-coated gold nanoparticles
      and the distribution and structure of their interfacial water molecules. The
      interactions of the mixed SAM-coated gold nanoparticles with water were analyzed
      by evaluating the radial distribution function, hydrogen bonds, the dipole
      orientations of the water molecules, and the water residence time in the
      interfacial region. The wettability of the mixed SAM-coated gold nanoparticles
      improved as the concentration of terminal hydroxy moieties was increased. The
      distribution and dynamics of the interfacial water molecules were found to be
      influenced by the mixing ratio of the terminal moieties of the SAM chains. The
      results of our simulations suggest that the surface interactions of the mixed SAM
      coated gold nanoparticles with the aqueous medium can be modulated by
      systematically altering the mixing ratio of the terminal methyl and hydroxy
      moieties. This work may lead to new biological and technological applications and
      inspire the development of novel biomimetic materials. Graphical Abstract Mixed
      SAM-coated gold nanoparticles. 

PMID- 25986773
TI  - Structures, stability, and electronic properties of novel superalkali-halogen
      clusters.
AB  - We have computationally designed some novel clusters by interaction of
      superalkali (SA) species (FLi2, OLi3, NLi4) with halogen (X = F, Cl) atoms. The
      ground state electronic structures of these superalkali-halogen (SA-X) clusters
      are identified and their stabilities are analyzed. The electronic properties of
      SA-X clusters are also discussed. Like alkali halides, these clusters can also be
      regarded as SA(+)X(-) species. We have noticed, however, that these clusters
      prefer to dissociate into ionic fragments, in contrast to alkali halides. The
      mean polarizabilities of SA-X clusters are much larger than alkali halides,
      reaching to 136.28 a.u. for NLi4-Cl, which further doubles in the case of its
      dimer, i.e., (NLi4-Cl)2. We believe that these SA-X clusters can be used as
      building blocks of novel materials, analogous to traditional alkali halides. 

PMID- 25986774
TI  - Towards thermally stable cyclophanediene-dihydropyrene photoswitches.
AB  - Cyclophanediene dihydropyrenes (CPD-DHP) are photochromic compounds because they
      change their color by irradiation with lights of different color. Potential use
      of CPD-DHP photoswitch in memory devices requires a very slow thermal return in
      the dark in the absence of any side reaction. Herein, thermal return of CPDs to
      DHPs, and an unwanted sigmatropic shift in DHP is studied through density
      functional theory calculations at (U)B3LYP/6-31+G(d). The thermal return occurs
      through symmetry forbidden conrotatory electrocyclic reaction. Dimethyl amino CPD
      DHP photoswitch pair has the highest activation barrier for electrocyclization
      and sigmatropic shifts. The lowest activation barrier for symmetry forbidden
      electrocyclization is observed for GeBr3 functionalized CPD. An unprecedented
      decomposition pathway involving elimination of the internal substituents is
      predicted for Cl, Br and SMe functionalized DHPs. This study shows great promise
      in understanding the Woodward Hoffmann forbidden processes and, in reducing the
      synthetic efforts toward robust photochromes for memory applications. 

PMID- 25986775
TI  - Interaction of a Ni(II) tetraazaannulene complex with elongated fullerenes as
      simple models for carbon nanotubes.
AB  - Nickel(II) complex of 5,14-dihydro-6,8,15,17-tetramethyldibenzo[b,i][1,4,8,11]
      tetraazacyclotetradecine (NiTMTAA), which can be employed for noncovalent
      functionalization of carbon nanotubes (CNTs), represents a more complex and
      interesting case in terms of structure of the resulting nanohybrids, as compared
      to the related materials functionalized with porphyrins and phthalocyanines. Due
      to its saddle shape, the NiTMTAA molecule adsorbed can adopt different,
      energetically non-equivalent orientations with respect to CNT, depending on
      whether CH3 or C6H4 groups contact the latter. The main goal of the present work
      was to provide information on the interactions of NiTMTAA with simple single
      walled CNT (SWNT) models accessible for dispersion-corrected DFT calculations.
      For reasons of comparison, we employed three such functionals: M06-2X and LC-BLYP
      as implemented in Gaussian 09 package, and PBE-G as implemented in Materials
      Studio 6.0. In order to roughly estimate the effect of nanotube chirality on the
      interaction strenght, we considered two short closed-end SWNT models (also
      referred to as 'elongated fullerenes'), one armchair and one zigzag, derived from
      C60 and C80 hemispheres. In addition, we calculated similar complexes with C60,
      as well as I h and D 5h isomers of C80. The results were analyzed in terms of
      optimized geometries, formation energies, HOMO-LUMO gap energies, and
      intermolecular separations. Graphical Abstract Interaction of Ni(II)
      tetraazaannulene complex with elongated fullerenes. 

PMID- 25986776
TI  - A theoretical prediction of the possible trigger linkage of CH3NO2 and NH2NO2 in
      an external electric field.
AB  - The effects of an external electric field on the C/N-NO2 bond with C/N-H and N-O
      bonds in CH3NO2 or NH2NO2 were compared using the DFT-B3LYP and MP2 methods with
      the 6-311++G(2d,p) and aug-cc-pVTZ basis sets. The results show that such fields
      have a minor effect on the C-N or C-H bond but a major effect on the N-O bond in
      CH3NO2, while in NH2NO2 electric fields affect the N-N bond greatly but the N-O
      or N-H bond only slightly. Thus, in CH3NO2, oxygen transfer or unimolecular
      isomerization to methyl nitrite might precede breaking of the C-N bond in the
      initial stages of decomposition, and the N-O bond could be the trigger bond in
      electric fields. In NH2NO2, however, N-N bond rupture may be preferential in an
      electric field and, consequently, the N-N bond might always be the real trigger
      bond. Atoms in molecules and natural bond orbital delocalization analyses,
      together with examination of shifts in electron density and frequencies support
      the above viewpoints. Forty-eight good linear correlations were found along the
      different field orientations at different levels of theory, including those
      between field strength (E) and changes in N-O/N-N bond length (DeltaR N-O/N-N),
      rho (N-O/N-N) values [Deltarho (N-O/N-N), or stretching frequencies of the N-O/N
      N bond (DeltaupsilonN-O/N-N). Graphical Abstract External electric fields have a
      major effect on the N-O or N-N bond inCH3NO2 or NH2NO2 , leading to a possible N
      O trigger bond inCH3NO2 or a real N-N trigger bond in NH2NO2 in an electric
      field. 

PMID- 25986777
TI  - Empirical and semi-analytical chlorophyll a algorithms for multi-temporal
      monitoring of New Zealand lakes using Landsat.
AB  - The concentration of chlorophyll a (chl a; as a proxy for phytoplankton biomass)
      provides an indication of the water quality and ecosystem health of lakes. An
      automated image processing method for Landsat images was used to derive chl a
      concentrations in 12 Rotorua lakes of North Island, New Zealand, with widely
      varying trophic status. Semi-analytical and empirical models were used to process
      137 Landsat 7 Enhanced Thematic Mapper (ETM+) images using records from 1999 to
      2013. Atmospheric correction used radiative transfer modelling, with atmospheric
      conditions prescribed with Moderate Resolution Imaging Spectroradiometer (MODIS)
      Terra and AIRS data. The best-performing semi-analytical and empirical equations
      resulted in similar levels of variation explained (r (2) = 0.68 for both
      equations) and root-mean-square error (RMSE = 10.69 and 10.43 MUg L(-1),
      respectively) between observed and estimated chl a. However, the symbolic
      regression algorithm performed better for chl a concentrations <5 MUg L(-1). Our
      Landsat-based algorithms provide a valuable method for synoptic assessments of
      chl a across the 12 lakes in this region. They also provide a basis for assessing
      changes in chl a individual lakes through time. Our methods provide a basis for
      cost-effective hindcasting of lake trophic status at a regional scale, informing
      on spatial variability of chl a within and between lakes.

PMID- 25986778
TI  - Discriminant analysis for characterization of hydrochemistry of two mountain
      river basins of contrasting climates in the southern Western Ghats, India.
AB  - Discriminant analysis (DA) was performed on river hydrochemistry data for three
      seasons (i.e., monsoon (MON), post-monsoon (POM), and pre-monsoon (PRM)) to
      examine the spatio-temporal hydrochemical variability of two mountain river
      basins (Muthirapuzha River Basin (MRB) and Pambar River Basin (PRB)) of the
      southern Western Ghats, India. Although the river basins drain tropical
      mountainous terrain, climate and degree of anthropogenic disturbances show
      significant differences (i.e., humid, more disturbed MRB vs semiarid, less
      disturbed PRB). In MRB, TDS, Na(+), pH, Mg(2+), and K(+) are the attributes
      responsible for significant hydrochemical variations between the seasons, while
      Cl(-), TH, and Na(+) are the predictors in PRB. The temporal discriminant models
      imply the importance of rainfall pattern, relative contribution of groundwater
      toward stream discharge and farming activities in hydrochemistry between the
      seasons. Inclusion of hydrochemical attributes (in the temporal discriminant
      functions) that can be derived from both natural and anthropogenic sources
      suggests that ionic enrichment strongly depends on the seasons, and is mainly due
      to the variability in the intensity of anthropogenic activities as well as
      fluctuations in river discharge. In spatial discriminant models, Cl(-) is the
      only variable responsible for hydrochemical variations between the basins (during
      MON), whereas Si discriminates during POM and PRM, implying the role of
      atmospheric supply, anthropogenic modifications as well as intensity of
      weathering. In the spatial discrimination models, misclassification of
      hydrochemistry data between MRB and PRB can be attributed to the overlapping
      effect of humid climate of MRB extending toward the upstream of (semiarid) PRB.
      This study underscores the versatility of DA in deciphering the significance of
      climatic controls on hydrochemical composition of tropical mountain rivers. 

PMID- 25986779
TI  - Job strain and changes in the body mass index among working women: a prospective
      study.
AB  - OBJECTIVE: The relationship between job strain and weight gain has been unclear,
      especially for women. Using data from over 52,000 working women, we compare the
      association between change in job strain and change in body mass index (BMI)
      across different levels of baseline BMI. SUBJECTS/METHODS: We used data from
      participants in the Nurses' Health Study II (n=52,656, mean age=38.4 years), an
      ongoing prospective cohort study. Using linear regression, we modeled the change
      in BMI over 4 years as a function of the change in job strain, baseline BMI and
      the interaction between the two. Change in job strain was characterized in four
      categories combining baseline and follow-up levels as follows: consistently low
      strain (low at both points), decreased strain (high strain at baseline only),
      increased strain (high strain at follow-up only) and consistently high strain
      (high at both points). Age, race/ethnicity, pregnancy history, job types and
      health behaviors at baseline were controlled for in the model. RESULTS: In
      adjusted models, women who reported high job strain at least once during the 4
      year period had a greater increase in BMI (DeltaBMI=0.06-0.12, P<0.05) compared
      with those who never reported high job strain. The association between the change
      in job strain exposure and the change in BMI depended on the baseline BMI level
      (P=0.015 for the interaction): the greater the baseline BMI, the greater the BMI
      gain associated with consistently high job strain. The BMI gain associated with
      increased or decreased job strain was uniform across the range of baseline BMI.
      CONCLUSIONS: Women with higher BMI may be more vulnerable to BMI gain when
      exposed to constant work stress. Future research focusing on mediating mechanisms
      between job strain and BMI change should explore the possibility of differential
      responses to job strain by initial BMI.

PMID- 25986780
TI  - Epileptic seizure as a trigger of acute coronary syndrome.

PMID- 25986781
TI  - A synthetic strategy to xylose-containing thioglycoside tri- and tetrasaccharide
      building blocks corresponding to Cryptococcus neoformans capsular polysaccharide
      structures.
AB  - As part of an ongoing project aimed at developing vaccine candidates against
      Cryptococcus neoformans the preparation of tri- and tetrasaccharide thioglycoside
      building blocks, to be used in construction of structurally defined part
      structures of C. neoformans GXM capsular polysaccharide, was investigated. Using
      a naphthalenylmethyl (NAP) ether as a temporary protecting group and
      trichloroacetimidate donors in optimized glycosylations the target building
      blocks, ethyl 6-O-acetyl-2,4-di-O-benzyl-3-O-(2-naphthalenylmethyl)-alpha-D
      mannopyranosyl-(1->3)-[2,3,4-tri-O-benzyl-beta-D-xylopyranosyl-(1->2)]-4,6-di-O
      benzyl-1-thio-alpha-D-mannopyranoside (16) and ethyl 2,3,4-tri-O-benzyl-beta-D
      xylopyranosyl-(1->2)-4,6-di-O-benzyl-3-O-(2-naphthalenylmethyl)-alpha-D
      mannopyranosyl-(1->3)-[2,3,4-tri-O-benzyl-beta-D-xylopyra-nosyl-(1->2)]-6-O
      acetyl-4-O-benzyl-1-thio-alpha-D-mannopyranoside (21), were efficiently prepared.
      These synthesized thiosaccharide building blocks were then used as donors in high
      yielding (~90%) DMTST promoted glycosylations to a spacer-containing acceptor to,
      after deprotection, afford GXM polysaccharide part structures ready for protein
      conjugation to give vaccine candidates. Also, the NAP groups in the building
      blocks were removed to obtain tri- and tetrasaccharide acceptors suitable for
      further elongation towards larger thiosaccharide building blocks.

PMID- 25986782
TI  - Disaster preparedness for children and families: a critical review.
AB  - Preparedness for disasters is universally low; children and families are
      particularly vulnerable groups. Against this backdrop, research on disaster
      preparedness for children and families is reviewed, with a focus on disaster
      preparedness and prevention education programs. Following definitions and
      theory/rationale, research is critically analyzed. While findings indicate a
      large growth in research in the past 15 years and largely positive findings,
      significant challenges remain. These challenges include issues related to
      methodological rigor, long-term effectiveness, and implementation. Recent
      research reflecting these important challenges is reviewed. At the same time,
      other recent research documents real potential for these programs, including
      findings which suggest that increased attention to incorporating theory- and
      evidence-supported components can enhance outcomes. Thus, despite some important
      limitations and challenges, research done to date signals promise for these
      programs in reducing risk and increasing resilience to disasters for children,
      families, and the households and communities in which they live.

PMID- 25986783
TI  - Cobalt(II) Complex of a Diazoalkane Radical Anion.
AB  - beta-Diketiminate cobalt(I) precursors react with diphenyldiazomethane to give a
      compound that is shown by computational studies to be a diazoalkane radical anion
      antiferromagnetically coupled to a high-spin cobalt(II) ion. Thermolysis of this
      complex results in formal N-N cleavage to give a cobalt(II) ketimide complex.
      Experimental evaluation of the potential steps in the mechanism suggests that
      free azine is a likely intermediate in this reaction. 

PMID- 25986784
TI  - Contribution of transcranial direct current stimulation on inhibitory control to
      assess the neurobiological aspects of attention deficit hyperactivity disorder:
      randomized controlled trial.
AB  - BACKGROUND: The applicability of transcranial direct current stimulation (tDCS)
      in individuals with attention deficit hyperactivity disorder (ADHD) has not yet
      been investigated. This low-cost, non-invasive, and safe technique optimized to
      modulate the inhibitory response might be a useful treatment option for those
      affected by this condition. OBJECTIVE: The aim of this single center, parallel,
      randomized, double-blinded, sham-controlled trial is to investigate the efficacy
      of transcranial direct current stimulation over the prefrontal cortex on the
      modulation of inhibitory control in adults with attention deficit hyperactivity
      disorder. METHODS: A total of 60 individuals will be divided into 2 groups by
      block randomization to receive active or sham stimulation. Anodal stimulation
      over the left dorsolateral prefrontal cortex will be applied at 1 mA during a
      single 20-minute session. Before and after interventions, subjects will perform 2
      go/no go tasks and the brain electrical activity will be recorded by
      electroencephalogram (EEG) with 32 channels, according to the 10-20 international
      EEG system. RESULTS: The trial began in May 2013 and we are currently performing
      the statistical analysis for the secondary outcomes. CONCLUSIONS: The findings
      from this study will provide preliminary results about the role of prefrontal
      cortex activation through tDCS on ADHD patients. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01968512; http://clinicaltrials.gov/ct2/show/NCT01968512
      (Archived by WebCite at www.webcitation.org/6YMSW2tkD).

PMID- 25986785
TI  - Evaluating the safety and efficacy of recombinant human thrombopoietin among
      severe sepsis patients with thrombocytopenia: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Sepsis is still a major health problem that causes high mortality in
      all populations. Organ dysfunction including sepsis-associated thrombocytopenia
      is prevalent among sepsis patients, resulting in increasing mortality rates.
      Considering the clinical role of platelets, thrombocytopenia in sepsis has led to
      a large spend in research activity and clinical trials in this area, yet there is
      no consensus upon which treatment should be administered. As a result, platelet
      transfusion is often indicated to resolve low platelet counts, leading to an
      increasing risk of the multiple risks transfusion brings, such as infectious or
      immune system complications. Given the role of thrombopoietin in stimulating
      proliferation and differentiation of megakaryocytes, our previous study
      investigated the potential benefits of recombinant human thrombopoietin in severe
      sepsis patients with thrombocytopenia. However, there are several limitations in
      the study, which may have led to bias in our conclusion. Thus, we are conducting
      this study in order to evaluate the safety and efficacy of recombinant human
      thrombopoietin in a large, varied population. METHODS/DESIGN: The study is
      designed as a randomized, open-label, placebo-controlled, multi-center study in
      tertiary academic centers for evaluating the safety and efficacy of recombinant
      human thrombopoietin over placebo. An established total of 708 patients with
      sepsis and thrombocytopenia will undergo prospective random assignment to
      recombinant human thrombopoietin or placebo (a 1:1 ratio). The primary endpoint
      is 7-day all-cause mortality and 28-day all-cause mortality. DISCUSSION: To our
      knowledge, this is the first study to evaluate the safety and efficacy of
      recombinant human thrombopoietin among severe sepsis patients with
      thrombocytopenia in a varied population. With our study, the level of evidence
      for the treatment of these patients will be significantly raised. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02094248 . Registration date: 23 March 2014.

PMID- 25986786
TI  - Re: Comparison of radiation dose from conventional and triple-bolus computed
      tomography urography protocols in the diagnosis and management of patients with
      renal cortical neoplasms.

PMID- 25986787
TI  - Re: Examining the relationship between operative time and hospitalization time in
      minimally invasive and open urologic procedures.

PMID- 25986788
TI  - Re: Intraoperative sonography during open partial nephrectomy for renal cell
      cancer: does it alter surgical management?

PMID- 25986789
TI  - Re: Long-term outcomes in patients with muscle-invasive bladder cancer after
      selective bladder-preserving combined-modality therapy: a pooled analysis of
      radiation therapy oncology group protocols 8802, 8903, 9506, 9706, 9906, and
      0233.

PMID- 25986790
TI  - Re: Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe,
      effective, and efficient neoadjuvant treatment for muscle-invasive bladder
      cancer: results of a multicenter phase II study with molecular correlates of
      response and toxicity.

PMID- 25986791
TI  - Re: Five-year nationwide follow-up study of active surveillance for prostate
      cancer.

PMID- 25986792
TI  - Re: The relationship between the extent of extraprostatic extension and survival
      following radical prostatectomy.

PMID- 25986793
TI  - Re: Patterns of declining use and the adverse effect of primary androgen
      deprivation on all-cause mortality in elderly men with prostate cancer.

PMID- 25986794
TI  - Re: Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide
      acetate in patients with localized high-risk prostate cancer: results of a
      randomized phase II neoadjuvant study.

PMID- 25986795
TI  - Re: A multinational, multi-institutional study comparing positive surgical margin
      rates among 22393 open, laparoscopic, and robot-assisted radical prostatectomy
      patients.

PMID- 25986796
TI  - Re: Hospital admissions after transrectal ultrasound-guided biopsy of the
      prostate in men diagnosed with prostate cancer: a database analysis in England.

PMID- 25986797
TI  - Re: Testosterone replacement therapy in men with prostate cancer: a time-varying
      analysis.

PMID- 25986798
TI  - Re: Low incidence of new biochemical hypogonadism after intensity modulated
      radiation therapy for prostate cancer.

PMID- 25986799
TI  - Re: Descriptive analysis of 30-day readmission after inpatient surgery discharge
      in the veterans health administration.

PMID- 25986800
TI  - Re: Metabolic evaluation and recurrence prevention for urinary stone patients:
      EAU guidelines.

PMID- 25986801
TI  - Re: Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis.

PMID- 25986802
TI  - Re: The ROKS nomogram for predicting a second symptomatic stone episode.

PMID- 25986803
TI  - Re: Quantification of asymptomatic kidney stone burden by computed tomography for
      predicting future symptomatic stone events.

PMID- 25986804
TI  - Re: High submuscular placement of urologic prosthetic balloons and reservoirs: 2
      year experience and patient-reported outcomes.

PMID- 25986805
TI  - Re: Risk factors for erosion of artificial urinary sphincters: a multicenter
      prospective study.

PMID- 25986806
TI  - Re: The fate of transitional urology patients referred to a tertiary transitional
      care center.

PMID- 25986807
TI  - Re: Buccal mucosal graft in reconstructive urology: uses beyond urethral
      stricture.

PMID- 25986808
TI  - Re: Use of "off the shelf" extracellular matrix graft materials for repair of
      testicular rupture: a novel technique.

PMID- 25986809
TI  - Re: Adult blunt renal trauma: routine follow-up imaging is excessive.

PMID- 25986810
TI  - Re: Lower genitourinary trauma in modern warfare: the experience from civil
      violence in Iraq.

PMID- 25986811
TI  - Re: Cystectomy with urinary diversion for benign disease: indications and
      outcomes.

PMID- 25986812
TI  - Re: Retained surgical sponges: findings from incident reports and a cost-benefit
      analysis of radiofrequency technology.

PMID- 25986813
TI  - Re: One-stop clinic for ketamine-associated uropathy: report on service delivery
      model, patients' characteristics and non-invasive investigations at baseline by a
      cross-sectional study in a prospective cohort of 318 teenagers and young adults.

PMID- 25986814
TI  - Re: Renal deterioration in multiple sclerosis patients with neurovesical
      dysfunction.

PMID- 25986815
TI  - Re: Urinary retention: benefit of gradual bladder decompression--myth or truth? A
      randomized controlled trial.

PMID- 25986816
TI  - Re: Cumulative use of strong anticholinergics and incident dementia: a
      prospective cohort study.

PMID- 25986817
TI  - Re: Association between self-reported urinary incontinence and musculoskeletal
      conditions in community-dwelling elderly women: a cross-sectional study.

PMID- 25986818
TI  - Re: Most older women recover baseline functional status following pelvic organ
      prolapse surgery.

PMID- 25986819
TI  - Re: Nocturia and sleep quality after transurethral resection of the prostate.

PMID- 25986820
TI  - Re: Monthly variation in acute urinary retention incidence among patients with
      benign prostatic enlargement in Taiwan.

PMID- 25986821
TI  - Re: Non-alcoholic fatty liver disease is associated with benign prostate
      hyperplasia in men and with overactive bladder in women.

PMID- 25986822
TI  - Re: Morbidity and mortality after benign prostatic hyperplasia surgery: data from
      the american college of surgeons national surgical quality improvement program.

PMID- 25986823
TI  - Re: Salivary testosterone measurement does not identify biochemical hypogonadism
      in aging men: a ROC analysis.

PMID- 25986824
TI  - Re: Dyspareunia and its comorbidities among Taiwanese women: analysis of the 2004
      2010 nationwide health insurance database.

PMID- 25986825
TI  - Re: Enclomiphene citrate stimulates testosterone production while preventing
      oligospermia: a randomized phase II clinical trial comparing topical
      testosterone.

PMID- 25986826
TI  - Re: Sexual dysfunction among reproductive-aged Chinese married women in Hong
      Kong: prevalence, risk factors, and associated consequences.

PMID- 25986827
TI  - Re: Livebirth after uterus transplantation.

PMID- 25986828
TI  - Re: Effects of varicocele on serum testosterone and changes of testosterone after
      varicocelectomy: a prospective controlled study.

PMID- 25986829
TI  - Re: Seminal BAX and BCL2 gene and protein expressions in infertile men with
      varicocele.

PMID- 25986830
TI  - Re: Generation of haploid spermatids with fertilization and development capacity
      from human spermatogonial stem cells of cryptorchid patients.

PMID- 25986831
TI  - Re: Changes in health care spending and quality 4 years into global payment.

PMID- 25986832
TI  - Re: Association between hospital conversions to for-profit status and clinical
      and economic outcomes.

PMID- 25986833
TI  - Re: Physician practice competition and prices paid by private insurers for office
      visits.

PMID- 25986834
TI  - Re: Ambulatory surgery centers and outpatient urologic surgery among Medicare
      beneficiaries.

PMID- 25986835
TI  - Re: Are high-care nursing home residents at greater risk of unplanned hospital
      admission than other elderly patients when exposed to beers potentially
      inappropriate medications?

PMID- 25986836
TI  - Re: Geriatric syndromes in individuals admitted to vascular and urology surgical
      units.

PMID- 25986837
TI  - Re: Role of urethral bulking agents in epispadias-exstrophy complex patients.

PMID- 25986838
TI  - Re: Epispadias in boys with an intact prepuce.

PMID- 25986839
TI  - Re: Utility of tissue expansion in pediatric phallic reconstruction: a 10-year
      experience.

PMID- 25986840
TI  - Re: Using the parents' video camera for the follow-up of children who have
      undergone hypospadias surgery decreases hospital anxiety of children.

PMID- 25986841
TI  - Re: Pretargeted dual-modality immuno-SPECT and near-infrared fluorescence imaging
      for image-guided surgery of prostate cancer.

PMID- 25986842
TI  - Re: Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer.

PMID- 25986843
TI  - Re: Identification and characterization of membrane androgen receptors in the
      ZIP9 zinc transporter subfamily: II. Role of human ZIP9 in testosterone-induced
      prostate and breast cancer cell apoptosis.

PMID- 25986844
TI  - Re: Protective effect of a beta3-adrenoceptor agonist on bladder function in a
      rat model of chronic bladder ischemia.

PMID- 25986845
TI  - Re: Chronic administration of anticholinergics in rats induces a shift from
      muscarinic to purinergic transmission in the bladder wall.

PMID- 25986848
TI  - Ambivalent binding between a radical-based pincer ligand and iron.
AB  - A complex exhibiting valence delocalization was prepared from 3,5-bis(2-pyridyl)
      1,2,4,6-thiatriazinyl (), an inherently redox active pincer-type ligand,
      coordinated to iron ( ()). Complex can be prepared via two routes, either from
      the reaction of the neutral radical with FeCl2 or by treatment of the anionic
      ligand () with FeCl3, demonstrating its unique redox behaviour. Electrochemical
      studies, solution absorption and solid-state diffuse reflectance measurements
      along with X-ray crystallography were carried out to elucidate the molecular and
      solid-state properties. Temperature- and field-dependent Mossbauer spectroscopy
      coupled with magnetic measurements revealed that exhibits an isolated S = 5/2
      ground spin state for which the low-temperature magnetic behaviour is dominated
      by exchange interactions between neighbouring molecules. This ground state is
      rationalized on the basis of DFT calculations that predict the presence of strong
      electronic interactions between the redox active ligand and metal. This
      interaction leads to the delocalization of beta electron density over the two
      redox active centres and highlights the difficulty in assigning formal charges to
      . 

PMID- 25986847
TI  - Genetic (co)variance of rainbow trout (Oncorhynchus mykiss) body weight and its
      uniformity across production environments.
AB  - BACKGROUND: When rainbow trout from a single breeding program are introduced into
      various production environments, genotype-by-environment (GxE) interaction may
      occur. Although growth and its uniformity are two of the most important traits
      for trout producers worldwide, GxE interaction on uniformity of growth has not
      been studied. Our objectives were to quantify the genetic variance in body weight
      (BW) and its uniformity and the genetic correlation (rg) between these traits,
      and to investigate the degree of GxE interaction on uniformity of BW in breeding
      (BE) and production (PE) environments using double hierarchical generalized
      linear models. Log-transformed data were also used to investigate whether the
      genetic variance in uniformity of BW, GxE interaction on uniformity of BW, and rg
      between BW and its uniformity were influenced by a scale effect. RESULTS:
      Although heritability estimates for uniformity of BW were low and of similar
      magnitude in BE (0.014) and PE (0.012), the corresponding coefficients of genetic
      variation reached 19 and 21%, which indicated a high potential for response to
      selection. The genetic re-ranking for uniformity of BW (rg = 0.56) between BE and
      PE was moderate but greater after log-transformation, as expressed by the low rg
      (-0.08) between uniformity in BE and PE, which indicated independent genetic
      rankings for uniformity in the two environments when the scale effect was
      accounted for. The rg between BW and its uniformity were 0.30 for BE and 0.79 for
      PE but with log-transformed BW, these values switched to -0.83 and -0.62,
      respectively. CONCLUSIONS: Genetic variance exists for uniformity of BW in both
      environments but its low heritability implies that a large number of relatives
      are needed to reach even moderate accuracy of selection. GxE interaction on
      uniformity is present for both environments and sib-testing in PE is recommended
      when the aim is to improve uniformity across environments. Positive and negative
      rg between BW and its uniformity estimated with original and log-transformed BW
      data, respectively, indicate that increased BW is genetically associated with
      increased variance in BW but with a decrease in the coefficient of variation.
      Thus, the scale effect substantially influences the genetic parameters of
      uniformity, especially the sign and magnitude of its rg.

PMID- 25986849
TI  - "Target-Site" Drug Metabolism and Transport.
AB  - The recent symposium on "Target-Site" Drug Metabolism and Transport that was
      sponsored by the American Society for Pharmacology and Experimental Therapeutics
      at the 2014 Experimental Biology meeting in San Diego is summarized in this
      report. Emerging evidence has demonstrated that drug-metabolizing enzyme and
      transporter activity at the site of therapeutic action can affect the efficacy,
      safety, and metabolic properties of a given drug, with potential outcomes
      including altered dosing regimens, stricter exclusion criteria, or even the
      failure of a new chemical entity in clinical trials. Drug metabolism within the
      brain, for example, can contribute to metabolic activation of therapeutic drugs
      such as codeine as well as the elimination of potential neurotoxins in the brain.
      Similarly, the activity of oxidative and conjugative drug-metabolizing enzymes in
      the lung can have an effect on the efficacy of compounds such as resveratrol. In
      addition to metabolism, the active transport of compounds into or away from the
      site of action can also influence the outcome of a given therapeutic regimen or
      disease progression. For example, organic anion transporter 3 is involved in the
      initiation of pancreatic beta-cell dysfunction and may have a role in how uremic
      toxins enter pancreatic beta-cells and ultimately contribute to the pathogenesis
      of gestational diabetes. Finally, it is likely that a combination of target
      specific metabolism and cellular internalization may have a significant role in
      determining the pharmacokinetics and efficacy of antibody-drug conjugates, a
      finding which has resulted in the development of a host of new analytical methods
      that are now used for characterizing the metabolism and disposition of antibody
      drug conjugates. Taken together, the research summarized herein can provide for
      an increased understanding of potential barriers to drug efficacy and allow for a
      more rational approach for developing safe and effective therapeutics. 

PMID- 25986850
TI  - Ginsenosides Regulate PXR/NF-kappaB Signaling and Attenuate Dextran Sulfate
      Sodium-Induced Colitis.
AB  - Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via
      repressing nuclear factor-kappaB (NF-kappaB); however, its overactivation may
      disrupt homeostasis of various enzymes and transporters. Here we found that
      ginsenosides restore PXR/NF-kappaB signaling in inflamed conditions without
      disrupting PXR function in normal conditions. The effects and mechanisms of
      ginsenosides in regulating PXR/NF-kappaB signals were determined both in vitro
      and in vivo. Ginsenosides significantly inhibited NF-kappaB activation and
      restored the expression of PXR target genes in tumor necrosis factor-alpha
      stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed
      NF-kappaB activation in a PXR-dependent manner. Ginsenosides significantly
      increased the physical association between PXR and the NF-kappaB p65 subunit and
      thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound
      K (CK) were major bioactive compounds in the regulating PXR/NF-kappaB signaling.
      Consistently, ginsenosides significantly attenuated dextran sulfate sodium
      induced experimental colitis, which was associated with restored PXR/NF-kappaB
      signaling. This study indicates that ginsenosides may elicit anti-inflammatory
      effects via targeting PXR/NF-kappaB interaction without disrupting PXR function
      in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in
      the discovery of new drugs that target PXR/NF-kappaB interaction in therapy for
      inflammatory bowel disease. 

PMID- 25986852
TI  - Intracellular Disassembly of Self-Quenched Nanoparticles Turns NIR Fluorescence
      on for Sensing Furin Activity in Cells and in Tumors.
AB  - There has been no report on enzyme-controlled disassembly of self-quenched NIR
      fluorescent nanoparticles turning fluorescence on for specific detection/imaging
      of the enzyme's activity in vitro and in vivo. Herein, we reported the rational
      design of new NIR probe 1 whose fluorescence signal was self-quenched upon
      reduction-controlled condensation and subsequent assembly of its nanoparticles
      (i.e., 1-NPs). Then disassembly of 1-NPs by furin turned the fluorescence on.
      Employing this enzymatic strategy, we successfully applied 1-NPs for NIR
      detection of furin in vitro and NIR imaging furin activity in living cells.
      Moreover, we also applied 1-NPs for discriminative NIR imaging of MDA-MB-468
      tumors in nude mice. This NIR probe 1 might be further developed for tumor
      targeted imaging in routine preclinical studies or even in patients in the
      future. 

PMID- 25986853
TI  - A multidisciplinary team approach minimises prophylactic mastectomy rates.
AB  - BACKGROUND: Prophylactic mastectomy (PM) has become increasingly common but is
      not without complications especially if accompanied by reconstructive surgery. In
      patients with sporadic unilateral breast cancer, contralateral PM offers no
      survival advantage. Multidisciplinary team (MDT) communication and interaction
      may facilitate shared decision-making and curtail PM rates. The aim of this study
      was investigate the effect of a regional MDT meeting on PM decision-making.
      METHODS: We conducted an observational study involving retrospective review of
      prospectively recorded MDT meeting records for a 151 patient requests for PM from
      2011 to 2014. Final MDT decisions were recorded as PM 'accepted', 'declined' or
      'pending'. For MDT sanctioned requests, the factors justifying PM were recorded.
      Where PM was declined, justification for MDT refusal was sought and recorded.
      RESULTS: Approximately half of all requests for PM have been upheld (53.0%) and
      1/3 of requests have been declined (32.5%). Of those declined, low risk of
      contralateral breast cancer versus relatively high risk of systemic relapse were
      commonly cited as justification for PM refusal (45.7%). A proportion of patients
      who initiated PM discussion subsequently changed their minds (19.6%), or failed
      to attend clinic appointments (6.5%). Some patients were deemed medically unfit
      for complex reconstructive surgery (13%), or were declined on the basis of an
      apparent cosmetic drive for surgery (6.5%), concerns regarding depression or
      anxiety (2.2%) and/or if family history could not be substantiated (6.5%).
      DISCUSSION: MDT meetings facilitate cross-specialty interrogation of requests for
      PM, minimise unnecessary surgery and restrict PM to those likely to derive
      maximum benefit.

PMID- 25986851
TI  - Targeting the IRE1alpha-XBP1 branch of the unfolded protein response in human
      diseases.
AB  - Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER)
      leads to ER stress, which is characteristic of cells with high level of secretory
      activity and implicated in a variety of disease conditions. In response to ER
      stress, the cell elicits an adaptive process called the unfolded protein response
      (UPR) to support cellular homeostasis and survival. However, prolonged and
      unsolvable ER stress also induces apoptosis. As the most conserved signaling
      branch of the UPR, the IRE1alpha-XBP1 pathway plays important roles in both
      physiological and pathological settings and its activity has profound effects on
      disease progression and prognosis. Recently, modulating this pathway with small
      molecule compounds has been demonstrated as a promising approach for disease
      therapy. In this review, we summarize a list of current investigational compounds
      targeting this pathway and their therapeutic features for treating human
      diseases. 

PMID- 25986854
TI  - Impact of axillary dissection in women with invasive breast cancer who do not fit
      the Z0011 ACOSOG trial because of three or more metastatic sentinel lymph nodes.
AB  - AIM: The objective of this study was to determine the effects of axillary lymph
      node dissection (ALND) versus sentinel lymph node biopsy alone (SLNB) on the
      survival of patients with 3 or more metastatic lymph nodes (MLN) in invasive
      breast cancer. METHODS: Data of 9521 patients with invasive T1-2M0 breast
      carcinoma and initial treatment with SLNB completed or not by ALND and 3 or more
      MLN were extracted from the SEER database. Univariate and multivariate analyses
      were performed. RESULTS: Overall, 9521 patients were included in the study. SLNB
      alone compared with ALND did not result in different overall survival (OS) or
      specific survival (SS) for patients with 3 or more MLN (p = 0.46 and 0.58,
      respectively). In subgroup analyses, OS was comparable between SLNB-alone and
      ALND when patients had only 3 or more than 3 MLN. When patients had 3 MLN, the 5
      year SS was significantly better for patients with ALND compared with SLNB-alone:
      91.5% and 85.1%, respectively (p = 0.02). The Hazard Ratio (HR) for OS comparing
      SLNB-alone with ALND adjusting for age, adjuvant radiotherapy, tumor size,
      estrogen receptor status, grade and tumor type resulted in an HR of 1.05 (95% CI,
      0.72-1.54, p = 0.77). CONCLUSION: In conclusion, patients with a T1-T2 invasive
      breast cancer and at least 3 MLN do not benefit from ALND after SLNB for specific
      and overall survival, thus limiting ALND to a staging procedure. A subgroup of
      patients with 3 MLN had a better SS with ALND, possibly due to an under-staging
      of the SLNB-alone group.

PMID- 25986855
TI  - Identifying the most appropriate age threshold for TNM stage grouping of well
      differentiated thyroid cancer.
AB  - OBJECTIVE: Age is integrated in most risk stratification systems for well
      differentiated thyroid cancer (WDTC). The most appropriate age threshold for
      stage grouping of WDTC is debatable. The objective of this study was to evaluate
      the best age threshold for stage grouping by comparing multivariable models
      designed to evaluate the independent impact of various prognostic factors,
      including age based stage grouping, on the disease specific survival (DSS) of our
      population-based cohort. METHODS: Data from population-based thyroid cancer
      cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow
      up of 11.5 years, was used to calculate DSS using the Kaplan Meier method.
      Multivariable analysis with Cox proportional hazard model was used to assess
      independent impact of different prognostic factors on DSS. The Akaike information
      criterion (AIC), a measure of statistical model fit, was used to identify the
      most appropriate age threshold model. Delta AIC, Akaike weight, and evidence
      ratios were calculated to compare the relative strength of different models.
      RESULTS: The mean age of the patients was 47.3 years. DSS of the cohort was 95.6%
      and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the
      lowest AIC, was identified as the best model. Akaike weight indicated an 85%
      chance that this age threshold is the best among the compared models, and is 16.8
      times more likely to be the best model as compared to a threshold of 45 years.
      CONCLUSION: The age threshold of 55 years was found to be the best for TNM stage
      grouping.

PMID- 25986857
TI  - Photoluminescence of a single quantum emitter in a strongly inhomogeneous
      chemical environment.
AB  - We present the results of a comprehensive photoluminescence study of defect
      centres in single SiO2 nanoparticles. We show that the photo-physical properties
      of the luminescent centres strongly resemble those of single dye molecules.
      However, these properties exhibit a large variability from particle to particle
      due to the different local chemical environment around each centre of each
      particle. This variability provides new insight into the complex photo-physics of
      single quantum emitters embedded into a random chemical environment. Moreover, a
      better understanding of the fundamental mechanism of the photoluminescence of
      defect centres in SiO2 structure is paramount for their application as white
      light sources, non-toxic labels for bio-imaging, or for combining them with
      metallic and semiconductor nanostructures. 

PMID- 25986856
TI  - Cell-free and concentrated ascites reinfusion therapy (CART) for management of
      massive malignant ascites in gastric cancer patients with peritoneal metastasis
      treated with intravenous and intraperitoneal paclitaxel with oral S-1.
AB  - BACKGROUND: Massive malignant ascites originating from peritoneal metastasis of
      gastric cancer is difficult to control and resistant to chemotherapy. Cell-free
      and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of
      apheresis therapy, by which filtered and concentrated ascites containing albumin
      and globulin is reinfused intravenously to patients. We retrospectively studied
      the feasibility of intraperitoneal (IP) chemotherapy combined with CART in
      gastric cancer patients with massive malignant ascites. METHODS: Paclitaxel (PTX)
      was administered via an IP access port implanted in the subcutaneous space. If
      patient had massive ascites at the start of treatment, paracentesis was performed
      through a percutaneous IP catheter and then CART was performed. PTX was
      administered through the catheter until the ascites diminished. RESULTS: A total
      of 127 CART procedures in 30 patients were analyzed. The average volume of
      processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g
      protein on average. Significant increases in urine volume, serum total protein
      and albumin level were found after the CART. Increase in body temperature (0.3
      degrees C), decrease in platelet count (3.8 * 10(4)/MUl), and changes in blood
      pressure (2 mm Hg) were found after the CART procedure, but no clinically
      significant adverse event was experienced. The median survival time and 1-year
      survival of 30 patients who received IP chemotherapy combined with the CART
      procedure was 10.2 months and 43.3% respectively. CONCLUSIONS: IP chemotherapy
      combined with CART might be a promising strategy for patients with massive
      malignant ascites originating from peritoneal metastasis of gastric cancer.

PMID- 25986858
TI  - Comparative clinico-haematological analysis in young Zebu cattle experimentally
      infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse
      infested areas of Northwest Ethiopia.
AB  - BACKGROUND: Ethiopia, particularly in the Northwest region, is affected by both
      tsetse and non-tsetse fly transmitted trypanosomosis, with significant impact on
      livestock productivity. The aim of this study was to determine and compare
      clinical findings and haematological values between experimental infections
      induced by Trypanosoma vivax isolates from areas of either transmission mode.
      Sixteen young (aged between 6 and 12 months) Zebu cattle (Bos indicus), purchased
      from a trypanosome-free area and confirmed to be trypanosome-negative, were
      randomly assigned into four groups of four animals. Groups 1, 2 and 3 were
      infected with an isolate from a tsetse infested or one of two isolates from a non
      tsetse infested area, and group 4 was a non-infected control. All animals in the
      infected groups were inoculated intravenously with 2 * 10(6) trypanosomes from
      donor animals. The experimental animals were monitored for eight consecutive
      weeks post infection for clinical signs, parasitaemia and haematological changes
      in packed cell volume (PCV), haemoglobin concentration (Hgb), total red blood
      cell (RBC) and white blood cell (WBC) counts, differential WBC count and blood
      indices (mean corpuscular volume [MCV], mean corpuscular haemoglobin and mean
      corpuscular haemoglobin concentration). RESULTS: Infection was characterized by
      reduced feed intake, weakness, pyrexia, parasitaemia, rough hair coat, enlarged
      prescapular lymph nodes, lacrimation, weight loss, pallor mucus membrane and
      dehydration. Body weight loss in all infected groups was significantly higher
      than in the non-infected control. Similarly, body weight loss was higher (P <
      0.001) in animals infected with the tsetse infested isolate than with the non
      tsetse infested isolates. The mean PCV, Hgb, total RBC and WBC counts were lower
      (P < 0.001), and mean MCV was higher (P = 0.01) in all infected groups than in
      non-infected control animals at different time points during the study period.
      Except for minor variations in haematological values, the overall changes were
      similar in all infected groups. CONCLUSION: Clinical signs and significant
      reduction in haematological values in the infected groups indicated the
      pathogenicity of the T. vivax parasites. Pathogenicity of T. vivax from the non
      tsetse infested area can be considered as nearly as important as that of its
      counterpart derived from the tsetse infested area.

PMID- 25986859
TI  - Preparation of a microporous organic polymer by the thiol-yne addition reaction
      and formation of Au nanoparticles inside the polymer.
AB  - A microporous polymer with sulfide and thiol groups was synthesized using the
      thiol-yne reaction. Au nanoparticles were prepared by in situ reduction reaction
      inside the polymer and were found to be well dispersed. The Au-containing polymer
      showed catalytic activity in the reduction of 4-nitrophenol. 

PMID- 25986860
TI  - Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle
      genes in MCF-7 cells.
AB  - Steroid receptor coactivator 2 (SRC-2) is a coactivator that regulates nuclear
      receptor activity. We previously reported that SRC-2 protein is degraded through
      the action of cAMP-dependent protein kinase A (PKA) and cAMP response element
      binding protein (CREB). In the study presented here, we aimed to identify
      proteins that interact with and thereby regulate SRC-2. We isolated cyclin C
      (CCNC) as an interacting partner with the SRC-2 degradation domain aa 347-758 in
      a yeast two-hybrid assay and confirmed direct interaction in an in vitro assay.
      The protein level of SRC-2 was increased with CCNC overexpression in COS-1 cells
      and decreased with CCNC silencing in COS-1 and MCF-7 cells. In a pulse-chase
      assay, we further show that silencing of CCNC resulted in a different SRC-2
      degradation pattern during the first 6 h after the pulse. Finally, we provide
      evidence that CCNC regulates expression of cell cycle genes upregulated by SRC-2.
      In conclusion, our results suggest that CCNC temporarily protects SRC-2 against
      degradation and this event is involved in the transcriptional regulation of SRC-2
      cell cycle target genes.

PMID- 25986861
TI  - Oncostatin M-dependent Mcl-1 induction mediated by JAK1/2-STAT1/3 and CREB
      contributes to bioenergetic improvements and protective effects against
      mitochondrial dysfunction in cortical neurons.
AB  - Oncostatin M (OSM), a cytokine in the interleukin-6 (IL-6) family, has been
      proposed to play a protective role in the central nervous system, such as
      attenuation of excitotoxicity induced by N-methyl-D-aspartate (NMDA) and
      glutamate. However, the potential neuroprotective effects of OSM against
      mitochondrial dysfunction have never been reported. In the present study, we
      tested the hypothesis that OSM may confer neuronal resistance against 3
      nitropropionic acid (3-NP), a plant toxin that irreversibly inhibits the complex
      II of the mitochondrial electron transport chain, and characterized the
      underlying molecular mechanisms. We found that OSM preconditioning dose- and time
      dependently protected cortical neurons against 3-NP toxicity. OSM stimulated
      expression of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 family
      member expressed in differentiating myeloid cells, that required prior
      phosphorylation of Janus kinase-1 (JAK1), JAK2, extracellular signal-regulated
      kinase-1/2 (ERK1/2), signal transducer and activator of transcription-3 (STAT3),
      STAT1, and cAMP-response element-binding protein (CREB). Pharmacological
      inhibitors of JAK1, JAK2, ERK1/2, STAT3, STAT1, and CREB as well as the siRNA
      targeting at STAT3 and Mcl-1 all abolished OSM-dependent 3-NP resistance.
      Finally, OSM-dependent Mcl-1 induction contributed to the enhancements of
      mitochondrial bioenergetics including increases in spare respiratory capacity and
      ATP production. In conclusion, our findings indicated that OSM induces Mcl-1
      expression via activation of ERK1/2, JAK1/2, STAT1/3, and CREB; furthermore, OSM
      mediated Mcl-1 induction contributes to bioenergetic improvements and
      neuroprotective effects against 3-NP toxicity in cortical neurons. OSM may thus
      serve as a novel neuroprotective agent against mitochondrial dysfunction commonly
      associated with pathogenic mechanisms underlying neurodegeneration. 

PMID- 25986862
TI  - Biphasic effect of PTK7 on KDR activity in endothelial cells and angiogenesis.
AB  - Protein tyrosine kinase 7 (PTK7) is a member of the defective receptor protein
      tyrosine kinase family which lacks catalytic activity. Expression of PTK7 is
      increased in various cancers but its role in carcinogenesis is not well
      understood. We previously showed that disruption of PTK7 function suppresses VEGF
      induced angiogenic phenotypes in HUVECs and mice. Here, we investigated molecular
      mechanisms for modulating VEGF-induced physiological effects by PTK7. Treatment
      with a high concentration of extracellular domain of PTK7 (soluble PTK7; sPTK7)
      or knockdown of PTK7 inhibited VEGF-induced phosphorylation of kinase insert
      domain receptor (KDR) but did not inhibit phosphorylation of fms-related tyrosine
      kinase 1 (FLT-1) in HUVECs. PTK7, more specifically sPTK7, interacted with KDR
      but not with FLT-1 in HUVECs and HEK293 cells. In vitro binding assay showed that
      sPTK7 formed oligomers with the extracellular domain of KDR (sKDR) up to an
      approximately 1:3 molar ratio, and vice versa. sPTK7 at lower molar ratios than
      sKDR enhanced the binding of VEGF to sKDR. At the same or higher molar ratios, it
      reduced the binding of VEGF to sKDR. Increasing concentrations of sPTK7 or
      increasing levels of PTK7 expression first increased and then decreased VEGF
      induced KDR phosphorylation, migration, and capillary-like tube formation of
      HUVECs, as well as in vivo angiogenesis. Taken together, our data demonstrates
      that PTK7 regulates the activity of KDR biphasically by inducing oligomerization
      of KDR molecules at lower concentrations and by surrounding KDR molecules at
      higher concentrations. 

PMID- 25986863
TI  - Lanostane-type triterpenoids from Abies faxoniana and their DNA topoisomerase
      inhibitory activities.
AB  - Nine lanostane-type triterpenoids were isolated from branches and leaves of Abies
      faxoniana, along with 10 known compounds. Two were isolated as inseparable
      mixtures of epimers at C-23 of the gamma-lactone ring that had a lactol
      structure. The structures of the nine compounds were established by spectroscopic
      analysis and circular dichroism (CD) data. The absolute configurations at the
      stereogenic centres of two of the known compounds were confirmed by X-ray
      crystallography. One compound showed cytotoxic activities against HCT-116, MCF-7,
      and A549 cells with IC50 values of 8.9, 7.6, and 4.2MUM, respectively. The
      isolated compounds were tested for their effects on human DNA topoisomerases I
      and II. One was found to be a selective inhibitor of human topo II activity with
      an IC50 value of 53.5MUM, which was comparable to that of the topo II inhibitor
      etoposide (IC50=49.6MUM). 

PMID- 25986864
TI  - A Long Non-coding RNA Activated by Transforming Growth Factor-beta is an
      Independent Prognostic Marker of Gastric Cancer.
AB  - BACKGROUND: A recent study reported that long non-coding RNA activated by TGF
      beta (lncRNA-ATB) induced epithelial-mesenchymal transition (EMT) through the
      transforming growth factor-beta (TGF-beta)/miR-200s/ZEB axis in hepatocellular
      carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in
      gastric cancer (GC) patients. MATERIALS AND METHODS: Quantitative reverse
      transcriptase polymerase chain reaction (qRT-PCR) was performed to examine
      expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183).
      Patients were divided into high and low lncRNA-ATB expression groups using a
      cutoff of lncRNA-ATB/GAPDH >=0.60 or <0.60 to determine the clinicopathological
      significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF
      beta, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines
      were treated by recombinant TGF-beta1 or TGF-beta receptor inhibitor to examine
      morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and
      ZEB1 levels, with respect to the EMT phenotype. RESULTS: The high lncRNA-ATB
      group experienced a lower overall survival rate compared with the low lncRNA-ATB
      group, and multivariate analysis indicated that lncRNA-ATB was an independent
      prognostic factor (hazard ratio 3.50; 95 % CI 1.73-7.44; p = 0.0004). miR-200c
      levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than
      in the low lncRNA-ATB group. Treatment with TGF-beta in GC cell lines resulted in
      morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and
      downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression.
      CONCLUSION: LncRNA-ATB plays an important role in EMT to promote invasion and
      metastasis through the TGF-beta/miR-200s/ZEB axis, resulting in a poor prognosis
      in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis
      in GC patients.

PMID- 25986865
TI  - Lymphatic Invasion is an Independent Adverse Prognostic Factor in Patients with
      Colorectal Liver Metastasis.
AB  - BACKGROUND: For a selection of patients with colorectal liver metastases (CRLM),
      liver resection is a curative option. In order to predict long-term survival,
      clinicopathologic risk scores have been developed, but little is known about
      histologic factors and their prognostic value for disease-free and overall
      survival. The objective of the present study was to assess possible prognostic
      histologic factors in patients with solitary CRLM treated with liver resection
      who did not receive neoadjuvant treatment. METHODS: Patients with solitary CRLM
      who underwent liver resection between 1992 and 2011 were evaluated for clinical
      prognostic factors. Histologic analyses on tumor thickness at the tumor-normal
      interface, presence of a fibrotic capsule, intrahepatic vascular invasion,
      lymphatic invasion, or bile duct invasion and perineural growth were performed,
      using immunohistochemistry. RESULTS: A total of 124 patients were analyzed with a
      median follow-up of 41 months (range 1-232 months). There was no association
      between histologic factors and disease-free survival in multivariate analysis. In
      multivariate analysis, intrahepatic lymphatic invasion was associated with a
      decreased overall survival (41.9 vs. 61.0 months; p = 0.041), especially in
      combination with vascular invasion (n = 15) (28.1 vs. 62.2 months; p < 0.0001).
      In addition, size over 50 mm (29.2 vs. 65.9 months; p = 0.004) and interval less
      than 12 months between resection of the primary tumor and diagnosis of liver
      metastasis (49.0 vs. 91.5 months: p = 0.019) were also independent adverse
      prognostic factors. CONCLUSIONS: Intrahepatic lymphatic invasion, especially in
      combination with vascular invasion, is an important adverse prognostic factor for
      overall survival in patients with solitary CRLM after liver resection.

PMID- 25986866
TI  - Incorporation of N0 Stage with Insufficient Numbers of Lymph Nodes into N1 Stage
      in the Seventh Edition of the TNM Classification Improves Prediction of Prognosis
      in Gastric Cancer: Results of a Single-Institution Study of 1258 Chinese
      Patients.
AB  - PURPOSE: This study examined the prognosis of the "node-negative with eLNs <= 15"
      designation and the additional value of incorporating it into the pN1 designation
      in the seventh edition of the N classification. METHODS: From January 2000 to
      September 2010, a total of 1258 gastric cancer patients (patients with eLNs > 15
      or node-negative with eLNs <= 15) undergoing radical gastric resection were
      enrolled in this study. We incorporated node-negative patients with eLNs <= 15
      into pN1 and compared this designation with the current 7th edition UICC N stage
      for 3, 5-year overall survival by univariate and multivariate analysis.
      Homogeneity, discriminatory ability, and monotonicity of gradients in the
      hypothetical N stage and the UICC N stage were compared using linear trend chi2,
      likelihood ratio chi2 statistics, and Akaike information criterion (AIC)
      calculations. RESULTS: Node-negative patients with eLNs <= 15 had worse survival
      compared with those with eLNs > 15. In univariate and multivariate analyses, the
      hypothetical N stage showed superiority to the 7th edition pN staging. The
      hypothetical staging system had higher linear trend and likelihood ratio chi (2)
      scores and smaller AIC values compared with those for the TNM system, which
      represented the optimum prognostic stratification. CONCLUSIONS: Node-negative
      patients with eLNs <= 15 can be considered to be incorporated into the pN1 stage
      in the 7th edition of the TNM classification.

PMID- 25986867
TI  - Feasibility and Nutritional Benefits of Laparoscopic Proximal Gastrectomy for
      Early Gastric Cancer in the Upper Stomach.
AB  - BACKGROUND: Laparoscopic proximal gastrectomy (LPG) has recently been applied for
      early gastric cancer (EGC) in the upper stomach as a minimally invasive and
      function-preserving surgery. This study aimed to clarify the feasibility and
      nutritional benefits of LPG over laparoscopic total gastrectomy (LTG). METHODS:
      This was a retrospective study of 77 patients with clinical stage I gastric
      cancer in the upper stomach. Of these patients, 25 underwent LPG, while 52
      underwent LTG. Surgical outcomes and postoperative nutritional status such as
      changes in body weight and blood chemistries were compared between LPG and LTG.
      RESULTS: Intraoperative blood loss and C-reactive protein levels at 3 and 7 days
      after surgery were significantly lower in LPG than in LTG (p = 0.018, 0.036, and
      0.042, respectively). No significant differences were observed in postoperative
      early or late complication rates between LPG and LTG. The incidence of Los
      Angeles Grade B or more severe reflux esophagitis after LPG was 9.1 %, which was
      similar to that after LTG (9.3 %). Postoperative changes in body weight at 6
      months and 1 and 2 years after surgery were consistently less in LPG than in LTG
      (p = 0.001, 0.022, and 0.001, respectively). Moreover, postoperative levels of
      hemoglobin and serum albumin and total lymphocyte count were also higher in LPG
      than in LTG. CONCLUSION: LPG may be a better choice for EGC in the upper stomach
      than LTG because it has distinct advantages in terms of surgical invasiveness and
      postoperative nutritional status.

PMID- 25986868
TI  - Theranostic Photosensitive Nanoparticles for Lymph Node Metastasis of Gastric
      Cancer.
AB  - BACKGROUND: Preoperative and intraoperative diagnoses of lymph node (LN)
      metastasis in patients with gastric cancer is essential to determine the extent
      of LN dissection in order to establish individualized treatment strategies. We
      investigated the theranostic value of a newly developed drug delivery system
      employing nanoparticles loaded with the indocyanine green (ICG) derivative ICG
      loaded lactosome (ICGm) using a murine draining LN metastasis model of gastric
      cancer. METHODS: In the experimental draining LN metastasis model of human
      gastric cancer, the right hind footpads of nude mice were injected with cancer
      cells. Three weeks later, either ICGm or ICG solution was injected through the
      tail vein. Forty-eight hours after the administration of a photosensitizer, in
      vivo and ex vivo imaging and photodynamic therapy (PDT) were performed, and size
      of the LNs was measured. RESULTS: In vivo imaging revealed metastatic LNs in the
      ICGm-treated mice but not in the ICG-treated mice. PDT using ICGm induced
      apoptosis and significantly inhibited the growth of metastatic LNs. CONCLUSIONS:
      ICGm presents a novel theranostic nanodevice for LN metastasis of gastric cancer.

PMID- 25986870
TI  - Postoperative Lower Extremity Edema in Patients with Primary Endometrial Cancer.
AB  - PURPOSE: The goal of this study was to investigate clinical manifestations of
      lower extremity edema (LEE) after lymph node dissection in patients with primary
      endometrial cancer. METHODS: Women with primary endometrial cancer who underwent
      staging surgery between November 2001 and March 2011 were included in the study.
      Medical records and/or responses to the Gynecologic Cancer Lymphedema
      Questionnaire (GCLQ) were used for LEE evaluation. RESULTS: All 154 patients
      underwent pelvic lymph node dissection, and 126 patients (81.8 %) underwent
      paraaortic LN dissection. The median age of the patients was 52 years, the
      majority had stage I cancer (78.6 %), and most had endometrioid histology (90.9
      %). The most frequent GCLQ responses were "experienced swelling" (35.7 %),
      "experienced numbness" (30.5 %), "experienced heaviness" (29.9 %), and
      "experienced aching" (29.9 %). Sixty-four patients (41.6 %) had previous (9/64,
      14.1 %) and/or current (55/64, 85.9 %) patient-reported LEE. Most patients
      developed LEE within 12 months after surgery (39/56, 69.6 %), and LEE lasted for
      more than 12 months in most patients (45/56, 80.4 %). Three patients reported
      recurrent LEE after recovery. Multivariate logistic regression identified the
      number of dissected pelvic lymph node (>=21) as a risk factor for LEE [odds ratio
      (OR) 3.28; 95 % confidence interval (CI) 1.058-10.136] and postoperative
      radiotherapy (OR 3.81, 95 % CI 1.67-8.69). CONCLUSIONS: LEE developed in more
      than one-third of patients with endometrial cancer after surgery, and LEE lasted
      for more than 12 months in most patients. A high number of dissected pelvic lymph
      nodes and postoperative radiotherapy is associated with LEE.

PMID- 25986869
TI  - Multidisciplinary Shared Decision Making in the Management of Ductal Carcinoma In
      Situ of the Breast.
AB  - BACKGROUND: Controversy continues regarding the use of adjuvant radiation therapy
      (RT) and hormonal therapy (HT) for patients undergoing breast-conserving therapy
      (BCT) for ductal carcinoma in situ (DCIS). METHODS: A prospective database was
      queried to identify women 18 years of age or older treated for DCIS from 2002 to
      2013. RESULTS: BCT was completed for 300 patients with a median age of 66 years.
      The median DCIS size was 0.7 cm (range 0.1-6.0 cm). The DCIS grades were high (44
      %), intermediate (37 %), and low (19 %). The closest margin was wider than 3 mm
      in 80 % and wider than 5 mm in 63 % of the cases. Adjuvant RT was administered to
      183 patients (61 %), and the RT status of 9 patients (3 %) was unknown. RT was
      associated with age, DCIS size, comedo necrosis, grade, and treatment in 2002
      2007 versus 2008-2013. Adjuvant HT was administered to 86 estrogen receptor
      positive patients (39 %), and the HT status of 4 patients (2 %) was unknown. The
      median follow-up period was 63 months (range 4-151 months). The 5-year overall
      local recurrence (LR) rate was 4 % (95 % confidence interval [CI] 2.1-7.4 %). The
      5-year LR rate was 3.9 % (95 % CI 1.8-8.6 %) for the RT patients and 4.1 % (95 %
      CI 1.6-10.7 %) for the patients not receiving RT. Of 13 LRs, 10 (77 %) were DCIS,
      and 3 (23 %) were invasive including one node-positive recurrence. CONCLUSIONS:
      Multidisciplinary and joint decision making in the treatment of DCIS results in a
      substantial and increasing number of patients forgoing adjuvant RT, adjuvant HT,
      or both. Reasonable 5-year LR rates suggest that such decision making can
      appropriately allocate patients to adjuvant therapies.

PMID- 25986871
TI  - Usefulness of Two-Dimensional Values Measured Using Preoperative Multidetector
      Computed Tomography in Predicting Lymph Node Metastasis of Gastric Cancer.
AB  - BACKGROUND: Multidetector computed tomography (MDCT) is essential for the
      prediction of lymph node (LN) metastasis in gastric cancer. However, the
      measurement method and size criteria for metastatic LNs using MDCT are unclear.
      METHODS: MDCTs of gastric cancer patients who underwent surgery and had
      pathological staging were reviewed by radiologists. The two-dimensional cutoff
      values for LNs with suspected metastasis were calculated, and clinicopathological
      data were analyzed using those cutoff values. RESULTS: The total number of
      enrolled patients was 327. The cutoff values of the maximal area with metastatic
      LNs were obtained significantly at stations 3, 4, and 6, and those values were
      112.09, 33.79, and 85.88 mm(2), respectively. The common cutoff value was 112.09
      mm(2), and the area under the curve was 0.617 (P = 0.002). The overall survival
      rate of the patients with LNs less than 112.09 mm(2) was significantly better
      than those with LNs greater than 112.09 mm(2) (P < 0.001). In multivariate
      analysis, the maximal LN area was an independent prognostic factor (adjusted
      hazard ratio, 1.697 [95% confidence interval 1.116-2.582]). CONCLUSIONS: Using
      two-dimensional values for LNs measured by MDCT is a practical method of
      predicting metastatic LNs in gastric cancer. The maximal LN area value would be
      useful in both the preoperative staging and prognosis prediction of gastric
      cancer.

PMID- 25986872
TI  - The Value of Ipsilateral Breast Tumor Recurrence as a Quality Indicator: Hospital
      Variation in the Netherlands.
AB  - PURPOSE: All Dutch hospitals are obliged to report their 5-year ipsilateral
      breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided
      that these rates should not exceed 5 %. This study determined the value of IBTR
      as an indicator to compare quality of care between hospitals. METHODS: All
      patients with breast cancer (pT1-3, any N, M0) who underwent surgery in 1 of 92
      Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer
      Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR
      rates for breast-conserving surgery (BCS) and mastectomy were calculated by using
      the Kaplan-Meier method. Hospital variation was presented in funnel plots.
      Multivariate analysis was used to assess hospital characteristics associated with
      IBTR rates. RESULTS: A total of 40,892 breast cancer patients were included. The
      overall 5-year IBTR rate was 2.85 % (95 % confidence interval 2.68-3.03) and was
      significantly lower for BCS than for mastectomy (2.38 vs. 3.45 %, p < 0.001).
      IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70
      % between hospitals. When random variation is taken into account, only extremely
      high IBTR rates can be detected as deviant from the target value of 5 %.
      Adjusting for tumor and patient characteristics, analyses showed that a higher
      volume of mastectomies is associated with lower IBTR rates. CONCLUSIONS: Our
      population-based findings show that IBTR rates in the Netherlands are low and
      have improved over time. The 5-year IBTR rate as an indicator for quality of care
      of individual hospitals is of limited value.

PMID- 25986873
TI  - The in vitro and in vivo investigation of inhaled migraine therapies using a
      novel aerosol delivery system consisting of an air pressurized capsule device
      (APCD) in combination with a pMDI spacer for endotracheal dosing into beagle
      dogs.
AB  - CONTEXT: Aerosol delivery to animals in preclinical settings has historically
      been very challenging, requiring the use of techniques, such as intratracheal
      instillation and dry powder insufflation, that are somewhat invasive, inefficient
      and not representative of clinical inhalation. OBJECTIVE: The objective of this
      work is to develop a system to deliver dry powder to dogs in an efficient and
      effective manner for the study of new anti-migraine compounds in development.
      MATERIALS AND METHODS: The new device uses a metered aliquot of a dry gas to
      force dry powder drug from a pre-filled HPMC capsule into an AeroChamber(r)
      spacer for subsequent inhalation by the animal. RESULTS: The delivery of two
      invesigational migraine drugs via the new device was assessed in vitro using
      abbreviated Andersen cascade impaction and showed the device is capable of
      generating a reproducible delivered dose of up to ~68% with more than 50% of the
      dose in the respirable range. In vivo studies have also been performed showing
      that this device effectively delivered the migraine drugs to spontaneously
      breathing dogs using a proprietary validated dog inhalation model. DISCUSSION:
      Results confirmed that the air pressurized capsule device (APCD) was effective in
      delivering the APIs to lungs of the animals. The in vivo data verified the
      advantages of inhaled delivery over oral delivery for this class of drugs and
      were used to establish the cardiopulmonary and respiratory side effect liability
      profile for these compounds. CONCLUSIONS: This work has demonstrated the utility
      of this device for quick and accurate screening of prospective drug candidates,
      representing a significant improvement in ease of use and reprodicibility over
      current delivery methods.

PMID- 25986874
TI  - Diabetes and risk of frailty and its potential mechanisms: a prospective cohort
      study of older adults.
AB  - BACKGROUND: There is emerging evidence of the role of diabetes as a risk factor
      for frailty. However, the mechanisms of this association are uncertain. METHODS:
      Prospective cohort study of 1750 noninstitutionalized individuals aged 60 years
      or older recruited in 2008-2010. At baseline, information was obtained on health
      behaviors, morbidity, cardiometabolic biomarkers, and antidiabetic treatments.
      Individuals were considered diabetic if they reported a physician diagnosis or
      had fasting serum glucose of 126 mg/dL or higher. Study participants were
      followed through 2012 to assess incident frailty, defined as at least 3 of the 5
      Fried criteria. RESULTS: At baseline, the cohort included 346 individuals with
      diabetes and 1404 without diabetes. Over a mean 3.5-year follow-up, 115 cases of
      incident frailty were ascertained. After adjustment for age, sex, and education,
      participants with diabetes showed an increased risk of frailty (odds ratio [OR]
      2.18, 95% confidence interval [CI] 1.42-3.37). Additional adjustment for health
      behaviors and abdominal obesity yielded a 29.7% reduction in the OR (OR 1.83, 95%
      CI 1.16-2.90). Subsequent adjustment for morbidity produced an additional 8.4%
      reduction (OR 1.76, 95% CI 1.10-2.82), and for cardiometabolic biomarkers, a
      further 44% reduction (OR 1.32, 95% CI 0.70-2.49). In particular, adjustment for
      HbA1c, lipoproteins, and triglycerides accounted for the greatest reductions.
      Finally, additional adjustment for oral antidiabetic medication reduced the OR to
      1.01 (95% CI 0.46-2.20), whereas adjustment for nutritional therapy increased the
      OR to 1.64 (95% CI 0.77-3.49). CONCLUSIONS: Diabetes mellitus is associated with
      higher risk of frailty; this association is partly explained by unhealthy
      behaviors and obesity and, to a greater extent, by poor glucose control and
      altered serum lipid profile among diabetic individuals. Conversely, diabetes
      nutritional therapy reduces the risk of frailty.

PMID- 25986875
TI  - Enterovirus D68 nosocomial outbreak in elderly people, France, 2014.

PMID- 25986876
TI  - A new technique to reduce incision size for removal of large cystic pelvic
      masses.

PMID- 25986877
TI  - New Photochrome Probe Allows Simultaneous pH and Microviscosity Sensing.
AB  - 4-N,N'-dimethylamino-4'-N'-stilbenemaleamic acid (DASMA), a unique molecular
      photochrome probe that exhibits solubility and retains trans-cis
      photoisomerisation in a wide range of organic solvents and aqueous pH
      environments, was prepared, purified and chemically characterised. Absorption,
      fluorescence excitation and emission spectra and constant-illumination
      fluorescence decay were measured in acetonitrile, dimethyl sulfoxide, ethanol,
      propylene carbonate, and aqueous glycerol mixtures. The pseudo-first-order
      fluorescence decay rates were found to be strongly dependent on the medium
      viscosity. In addition, the molecule exhibited the pH-dependent fluorescence and
      photoisomerisation kinetics. 

PMID- 25986878
TI  - An ICT-Based Hydrogen Sulfide Sensor with Good Water Solubility for Fluorescence
      Imaging in Living Cells.

PMID- 25986879
TI  - Meningococcal vaccines: Current state and future outlook.
AB  - Neisseria meningitidis infections are a major public health problem worldwide.
      Although conventional approaches have not led to development of a serogroup B
      meningococcal vaccine, a new technique based on genome sequencing has created new
      perspectives. Recently, a universal serogroup B meningococcal vaccine,
      Bexsero((r)), was licensed in Europe, Australia and United States, following
      several clinical studies demonstrating its immunogenicity and safety.
      Availability of this vaccine could contribute positively to human health, by
      significantly reducing the incidence of meningococcal infections. However,
      unfavorable cost-effectiveness analysis means that routine vaccination is not
      currently recommended. Another serogroup meningococcal vaccine, Trumemba((r)),
      was also recently licensed in United States. Like any drug, Bexsero((r)) and
      Trumemba((r)) will require close observation to assess their impact on
      meningococcal epidemiology. 

PMID- 25986881
TI  - Making a Case to Reduce Legal Impediments to Midwifery Practice in the United
      States.

PMID- 25986880
TI  - Building Capacity to Address Women's Health Issues in the Mixtec and Zapotec
      Community.
AB  - INTRODUCTION: Mixtecs and Zapotecs are indigenous populations from Mexico. Many
      are unable to read and write, and speak only their native nonwritten languages,
      Mixteco and Zapoteco. About one-half of California's indigenous farm worker
      population is estimated to be Mixteco-speaking (82,000-125,000), and about 20,000
      Mixtecs and a smaller number of Zapotecs live in Ventura County. OBJECTIVES: A
      community-academic partnership conducted mixed-methods research with the aims of
      1) collecting preliminary data on women's health needs, 2) training promotoras to
      assist with this effort, and 3) engaging community members and obtaining their
      input through community dialogues. METHODS: Promotoras who were bilingual in
      Spanish and either Mixteco or Zapoteco were trained to conduct surveys that
      included questions on breast feeding and receipt of breast and cervical cancer
      screening examinations. Barriers to and facilitators of women obtaining these
      cancer screening tests were discussed in small groups. RESULTS: In 2013, 813
      Mixtec and Zapotec women completed surveys. Although most women reported breast
      feeding (94%), and receipt of a pelvic examination (85%) and a breast examination
      (72%), only 44% of women 40 years and older had ever heard of and 33% had ever
      had a mammogram. Community members recommended offering free mammograms on the
      weekend by female providers, having women accompanied by promotoras who can
      translate, conducting door-to-door outreach, advertising cancer screening on the
      radio and providing small incentives to women. DISCUSSION: Trained bilingual
      promotoras can assist in increasing the capacity of indigenous communities to
      conduct collaborative research by engaging community members and collecting local
      data.

PMID- 25986882
TI  - The new InsP3Kinase inhibitor BIP-4 is competitive to InsP3 and blocks
      proliferation and adhesion of lung cancer cells.
AB  - As ectopic expression of the neuronal inositol-1,4,5-trisphosphate-3-kinase A
      (InsP3Kinase) in tumor cells increases the metastatic potential, InsP3Kinase is
      an interesting target for tumor therapy. Recently, we have identified a membrane
      permeable InsP3Kinase inhibitor (BAMB-4) exhibiting an IC50-value of 20 MUM. Here
      we characterized a new InsP3Kinase inhibitor which shows a 130-fold lower IC50
      value (157 +/- 57 nM) as compared to BAMB-4. We demonstrate that this
      nitrophenolic compound, BIP-4, is non-competitive to ATP but competitive to
      InsP3, thus exhibits a high selectivity for inhibition of InsP3Kinase activity.
      Docking analysis suggested a putative binding mode of this molecule into the
      InsP3Kinase active site. Determination of cellular uptake in lung cancer cells
      (H1299) revealed that 6% of extracellular BIP-4 is internalized by non-endosomal
      uptake, showing that BIP-4 is not trapped inside endo/lysosomes but is available
      to inhibit cellular InsP3Kinase activity. Interestingly, we found that BIP-4
      mediated inhibition of InsP3Kinase activity in the two lung cancer cell lines
      H1299 and LN4323 inhibited proliferation and adhesion at IC50 values of 3 MUM or
      2 MUM, respectively. InsP3Kinase inhibition did not alter ATP-induced calcium
      signals but significantly reduced the level of Ins(1,3,4,5,6)P5. From these data
      we conclude that the inhibitory effect of BIP-4 on proliferation and adhesion of
      lung cancer cells does not result from alterations of calcium but from
      alterations of inositol phosphate signals. In summary, we reveal that inhibition
      of cellular InsP3Kinase by BIP-4 impairs proliferation and adhesion and therefore
      BIP-4 might be a promising compound to reduce the metastatic potential of lung
      carcinoma cells.

PMID- 25986883
TI  - Pharmacokinetic interactions of breast cancer chemotherapeutics with human
      doxorubicin reductases.
AB  - Paclitaxel (PTX), docetaxel (DTX), 5-fluorouracil (5-FU), cyclophosphamide (CYC)
      or tamoxifen (TMX) are combined with doxorubicin (DOX) in first-line chemotherapy
      regimens that are indicated for breast cancer patients. Although the efficacies
      of these drugs in combination treatments have been demonstrated in clinical
      practice, their possible interference with DOX metabolism has not been described
      in detail to date. In the present study, we investigated the possible
      interactions of human carbonyl reducing enzymes with 5-FU, PTX, DTX, CYC and TMX.
      First, the reducing activities of carbonyl reducing enzymes toward DOX were
      tested using incubations with purified recombinant enzymes. In the subsequent
      studies, we investigated the possible effects of the tested anticancer agents on
      the DOX-reducing activities of the most potent enzymes (AKR1C3, CBR1 and AKR1A1)
      and on the DOX metabolism driven by MCF7, HepG2 and human liver cytosols. In both
      of these assays, we observed that CYC and its active metabolites inhibited DOX
      metabolism. In the final study, we tracked the changes in AKR1C3, CBR1 and AKR1A1
      expression levels following exposure to the tested cytostatics in MCF7 and HepG2
      cells. Consequently, no significant changes in the expression levels of tested
      enzymes were detected in either cell line. Based on these findings, it is
      feasible to presume that inhibition rather than induction plays a role in the
      interactions of the tested anticancer agents with DOX-reducing enzymes. In
      conclusion, our results describe important molecular events that occur during
      combination breast cancer therapies and might modulate pharmacokinetic DOX
      resistance and/or behaviour. 

PMID- 25986884
TI  - Lipid transport in Mycobacterium tuberculosis and its implications in virulence
      and drug development.
AB  - Tuberculosis is still a major health problem worldwide and one of the main causes
      of death by a single infectious agent. Only few drugs are really effective to
      treat tuberculosis, hence, the emergence of multiple, extensively, and totally
      drug resistant bacilli compromises the already difficult antituberculosis
      treatments. Given the persistent global burden of tuberculosis, it is crucial to
      understand the underlying mechanisms required for the pathogenicity of
      Mycobacterium tuberculosis (Mtb), the causal agent of tuberculosis, in order to
      pave the way for developing better drugs and strategies to treat and prevent
      tuberculosis. The exclusive mycobacterial cell wall lipids such as trehalose
      monomycolate and dimycolate (TMM, TDM), phthiocerol dimycocerosate (PDIM),
      sulpholipid-1 (SL-1), diacyl trehalose (DAT), and pentacyl trehalose (PAT), among
      others, are known to play an important role in pathogenesis; thus, proteins
      responsible for their transport are potential virulence factors. MmpL and MmpS
      proteins mediate transport of important cell wall lipids across the mycobacterial
      membrane. In Mtb, MmpL3, MmpL7 and MmpL8 transport TMM, PDIM and SL-1
      respectively. The translocation of DAT and biosynthesis of PAT is likely due to
      MmpL10. MmpL and MmpS proteins are involved in other processes such as drug
      efflux (MmpL5 and MmpL7), siderophore export (MmpL4/MmpS4 and MmpL5/MmpS5), and
      heme uptake (MmpL3 and MmpL11). Altogether, these proteins can be regarded as new
      potential targets for antituberculosis drug development. We will review recent
      advances in developing inhibitors of MmpL proteins, in the challenging context of
      targeting membrane proteins and the future prospects for potential
      antituberculosis drug candidates. 

PMID- 25986885
TI  - Dopamine D2 and angiotensin II type 1 receptors form functional heteromers in rat
      striatum.
AB  - Identification of G protein-coupled receptors and their specific function in a
      given neuron becomes essential to better understand the variety of signal
      transduction mechanisms associated with neurotransmission. We hypothesized that
      angiotensin II type 1 (AT1) and dopamine D2 receptors form heteromers in the
      central nervous system, specifically in striatum. Using bioluminescence resonance
      energy transfer, a direct interaction was demonstrated in cells transfected with
      the cDNA for the human version of the receptors. Heteromerization did not affect
      cAMP signaling via D2 receptors but attenuated the coupling of AT1 receptors to
      Gq. A common feature of heteromers, namely cross-antagonism, i.e. the blockade of
      the signaling of one receptor by the blockade of the partner receptor, was tested
      in co-transfected cells. Candesartan, the selective AT1 receptor antagonist, was
      able to block D2-receptor mediated effects on cAMP levels, MAP kinase activation
      and beta-arrestin recruitment. This effect of candesartan, which constitutes a
      property for the dopamine-angiotensin receptor heteromer, was similarly occurring
      in primary cultures of neurons and rat striatal slices. The expression of
      heteromers in striatum was confirmed by robust labeling using in situ proximity
      ligation assays. The results indicate that AT1 receptors are expressed in
      striatum and form heteromers with dopamine D2 receptors that enable drugs
      selective for the AT1 receptor to alter the functional response of D2 receptors. 

PMID- 25986887
TI  - [Neuroendocrine tumors].

PMID- 25986888
TI  - [The 99th annual conference of the German Society of Pathology : Frankfurt am
      Main, 28-31 May 2015].

PMID- 25986886
TI  - [Neuroendocrine neoplasms of the breast].
AB  - Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities.
      According to the literature up to 5% of breast neoplasms are malignant epithelial
      neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture
      and cytology combined with an expression of the neuroendocrine vesicle markers
      chromogranin A and/or synaptophysin. The diagnosis is supplemented by the
      receptor status and the proliferative activity. According to the World Health
      Organization (WHO) classification of 2012 the following groups of NEN are
      distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well
      differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small
      cell carcinoma (NEC). This review article focuses on (1) the definition and basic
      principles of diagnostics, (2) the history, nomenclature and WHO classification
      from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary
      background and functional activity, (5) the expression of receptors and (6) the
      possible clinical implications. In addition, the first results of a retrospective
      single center study (n = 465 patients with breast cancer over a time period of 4
      years) on the frequency of NEN of the breast at the Breast Center of the
      University Hospital Dusseldorf are presented. In this study a frequency of 4.5%
      of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or
      synaptophysin positive tumor cells.

PMID- 25986889
TI  - Right hepatectomy for giant hepatic hemangioma with progressive growth in a case
      of relative hyperestrogenism.

PMID- 25986890
TI  - Perforated hemorrhagic cholecystitis.

PMID- 25986891
TI  - miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells
      via AKT activation.
AB  - BACKGROUND: Pertuzumab is a humanized mAb that binds to the extracellular region
      of HER2/ErbB2 and is approved for treating breast cancer. Although ovarian cancer
      and breast cancer have comparable levels of HER2/ErbB2 expression, clinical
      studies of pertuzumab in epithelial ovarian cancer patients have not met the same
      level of success. OBJECTIVES: To investigate the molecular mechanisms by which
      pertuzumab exerts its anti-tumor effects in ovarian cancer and the mechanisms by
      which cancer cells achieve pertuzumab resistance. METHODS: We examined expression
      of miR-150 in ovarian cancer cells treated with pertuzumab or not. miR-150
      knockdown impacts on pertuzumab treatment were analyzed by cell proliferation
      assay, apoptosis analysis and cell cycle analysis. Cell signal pathway was
      examined by western blot assay. RESULTS: Pertuzumab induced miRNA-150 expression
      in SKOV3 and SNU119 cells. Furthermore, suppression of miRNA-150 in both cell
      lines resulted in decreased drug sensitivity to pertuzumab and cell apoptosis.
      The blockage of G1/S checkpoint by pertuzumab was rescued as well. miRNA-150
      knockdown activated PI3K-Akt pathway and LY294002 reversed the effect of miR-150
      knockdown. CONCLUSIONS: miRNA-150 downregulation may contribute to the pertuzumab
      resistance in ovarian cancer via, at least in part, PI3K-akt pathway.

PMID- 25986892
TI  - Evaluation of the prognostic significance of disseminated tumor cells in the bone
      marrow of primary, non-metastatic breast cancer patients after a 7-year follow
      up.
AB  - PURPOSE: About 30% of primary, non-metastatic breast cancer patients show a
      relapse of the disease years after first diagnosis, probably due to early tumor
      cell spread to the bone marrow (BM). For disseminated tumor cells (DTCs) in the
      BM, tumor cell dormancy, stem cell-like features and discordant receptor status
      of DTCs as compared to the primary tumor have been described, explaining the
      failure of conventional therapies. Here, we demonstrate no prognostic impact of
      DTCs and explain these findings by early bisphosphonate intake. METHODS: Bone
      marrow aspirates of 394 patients with first diagnosis of breast cancer diagnosed
      between July 1997 and February 2003 were evaluated for DTCs, applying
      immunocytochemistry. In addition to the given therapy including chemotherapy,
      radiotherapy and anti-hormonal therapy, oral clodronate therapy was recommended
      for at least 2 years for all DTC-positive patients. BM results were correlated
      with clinical prognostic factors and overall survival (OS). RESULTS: Disseminated
      tumor cells were detected in 163/394 (41%) patients and significantly correlated
      with a histopathological lobular subtype (p = 0.032) and inversely with HER2
      positivity (p = 0.01). After a median follow-up of 7 years, no significant
      differences with regard to OS could be demonstrated for DTC-positive patients as
      compared to patients with no DTCs in the BM at first diagnosis (p = 0.156).
      CONCLUSIONS: In this study, we demonstrate no prognostic impact of DTCs,
      contradictory to previous findings. We speculate that the lack of impact of DTC
      positivity on OS might be due to early clodronate intake, but further studies
      will have to prove whether the observed effect can be confirmed.

PMID- 25986893
TI  - Maternal plasma TIMP-4 levels combined with clinical risk factors for the early
      prediction of pregnancy-induced hypertension.
AB  - OBJECTIVE: The objective of this study was to create a model for early predicting
      pregnancy-induced hypertension (PIH) using plasma markers and clinical risk
      factors. METHODS: A nested case-control study was performed at the Laboratory
      Department of Guangzhou Women and Children's Medical Center. From a prospective
      cohort of tens of thousands of unselected women with singleton pregnancies at 8
      20 weeks gestation, maternal plasma samples were obtained from 73 women who
      subsequently developed PIH (PIH group) and 146 gestational age- and maternal age
      matched women with normotensive pregnancies (control group). Proteins extracted
      from the plasma samples were screened by microchip and verified by ELISA.
      Clinical risk factor data were analyzed retrospectively. RESULTS: Compared to the
      control group, high concentrations of tissue inhibitor of metalloproteinase-4
      (TIMP-4) were found in women with PIH (P = 0.000). Univariate risk factor
      analysis identified three variables with significant differences between the
      groups: family history of PIH (P = 0.031), body mass index (BMI; P < 0.001), and
      non-glucose-6-phosphate dehydrogenase deficiency-induced anemia (P < 0.027).
      Multiple regression analyses revealed a significant relationship of PIH with TIMP
      4 levels, BMI, and family history (combined area under the receiver operating
      characteristic curve = 0.820). CONCLUSION: Upregulation of plasma TIMP-4 might
      contribute to PIH processes. Potential risk factors of this disease may include a
      family history of PIH and BMI. The combination of TIMP-4 levels and these risk
      factors may have some predictive values for PIH. Future multicenter studies
      including greater numbers of samples, analyzed proteins, and risk factors are
      needed to obtain a higher predictive value of the model for the clinical
      diagnosis of PIH.

PMID- 25986894
TI  - Surgical technique of a recurrent post-radiation vesicovaginal fistula with a
      small intestine graft.
AB  - Vesicovaginal fistulas are devastating conditions for the affected women. The
      combination of a hysterectomy and radiation increases the fistula risk 5-10
      times. Radiation-induced recurrent vesicovaginal fistulas have the lowest success
      rate and require the most demanding treatment. We present the case of a recurrent
      post-radiation vesicovaginal fistula treated with a small intestine graft after
      unsuccessful conservative and failed previous operative treatments. The surgical
      management with a small intestine graft led to a permanently closed fistula. We
      describe the surgical abdominal procedure step-wise and review the rather scarce,
      post-radiation fistula literature. The closure of a vesicovaginal fistula with a
      small intestine graft is a complex surgical treatment with a long-term,
      successful result. 

PMID- 25986895
TI  - Ibni Sina (Avicenna) the most known and greatest Turkish medical doctor in late
      ancient world.

PMID- 25986896
TI  - Response to: Avicenna, a Persian scientist.

PMID- 25986897
TI  - Prevalence and Causes of Visual Impairment in a Chinese Adult Population: The
      Taizhou Eye Study.
AB  - PURPOSE: To study the current prevalence and causes of low vision and blindness
      in an adult Chinese population. DESIGN: Population-based, cross-sectional study.
      PARTICIPANTS: We used a random cluster sampling method and evaluated 10 234
      eligible subjects >=45 years old (response rate, 78.1%) in the Taizhou Eye Study.
      METHODS: Examinations were performed from July 2012 through December 2013.
      Participants underwent a detailed examination, including uncorrected visual
      acuity, best-corrected visual acuity (BCVA), intraocular pressure, axial length,
      slit-lamp, and fundus examinations to evaluate the prevalence and primary causes
      of visual impairment (VI). MAIN OUTCOME MEASURES: We defined low vision and
      blindness according to the World Health Organization (WHO) criteria (low vision:
      BCVA, <20/63->=20/400; blindness: BCVA, <20/400 in the better eye) and United
      States criteria (low vision: BCVA, <20/40->=20/200; blindness: BCVA, <20/200 in
      the better eye). RESULTS: Using the WHO BCVA criteria, the standardized
      prevalence of bilateral low vision and blindness were 5.1% and 1.0%,
      respectively. Using the United States BCVA criteria, the standardized prevalence
      were 12.8% and 1.5%, respectively. Using the WHO criteria, the primary causes of
      bilateral low vision and blindness were cataract (59.1% and 48.5%, respectively),
      myopic macular degeneration (17.6% and 17.2%, respectively), and age-related
      macular degeneration (11.6% and 10.1%, respectively). The primary causes of
      monocular low vision were cataract (55.6%), age-related macular degeneration
      (12.6%), and myopic macular degeneration (8.9%), whereas those of monocular
      blindness were cataract (46.8%), atrophy of eyeball or prosthetic eye (10.2%),
      and cornea opacity (7.3%). A further analysis revealed that in adults 45-59 years
      old, myopic macular degeneration (59.6% and 27.2%, respectively) and cataract
      (13.8% and 23.4%, respectively) were the leading causes of bilateral and
      monocular VI. In adults >=60 years old, cataract (66.8% and 61.2%, respectively)
      and age-related macular degeneration (12.6% and 11.8%, respectively) were the
      primary causes of bilateral and monocular VI. CONCLUSIONS: The prevalence of low
      vision and blindness in Chinese adults remains a severe public health problem. In
      the Taizhou Eye Study, cataract was the leading cause of low vision and
      blindness. Myopic macular degeneration and cataract were the primary causes of VI
      in adults 45-59 years and >=60 years old, respectively.

PMID- 25986898
TI  - Comparison of Clinical Features in Highly Myopic Eyes with and without a Dome
      Shaped Macula.
AB  - PURPOSE: To compare the clinical features of highly myopic eyes with a dome
      shaped macula (DSM) with those without a DSM and to identify the funduscopic
      clues to suspect the presence of DSM. DESIGN: Retrospective case series.
      PATIENTS: A total of 586 patients (1118 eyes) with high myopia (refractive error
      <-8 diopters [D] or axial length >=26.5 mm) who had optical coherence tomography
      (OCT) examinations through the central fovea at our High Myopia Clinic between
      February 2012 and November 2013. METHODS: Vertical and horizontal OCT scans
      across the central fovea were retrospectively analyzed. A DSM was defined by the
      presence of an inward bulge of >50 MUm in the vertical OCT image. Fundus
      photographs also were analyzed to identify the funduscopic clues to suspect the
      presence of DSM. MAIN OUTCOME MEASURES: The rate of DSM in 1118 highly myopic
      eyes. The rate of DSM in highly myopic eyes with macular complications.
      Funduscopic features to suggest the presence of DSM. RESULTS: Among the 1118
      eyes, 225 (20.1%) had a DSM. A DSM was present in both vertical and horizontal
      OCT sections in 20% of eyes, along only the vertical section in 77% of eyes, and
      in only the horizontal section in 2% of eyes. The results of multiple regression
      analyses showed that serous retinal detachment and foveal and extrafoveal
      retinoschisis were significantly associated with the presence of DSM and that
      choroidal neovascularization was not. Ophthalmoscopically, 91.4% of the eyes with
      the appearance of a horizontal ridge connecting the optic disc and the fovea had
      a DSM. CONCLUSIONS: A DSM is found in as many as 20% of highly myopic
      individuals. Horizontal ridges connecting the optic disc and the fovea might be
      an important clue to suspect the presence of a DSM on the basis of fundus
      photographs.

PMID- 25986899
TI  - Association between bone marrow stromal cell antigen 1 gene polymorphisms and the
      susceptibility to Parkinson's disease: a meta-analysis.
AB  - A number of studies have investigated the association between Parkinson's disease
      (PD) and genetic polymorphisms of bone marrow stromal cell antigen 1 (BST-1).
      However, the results to date have been conflicting. In this study a meta-analysis
      was performed to assess the association between BST-1 polymorphisms and PD.
      Previous relevant studies were identified from Medline, Embase and Cochrane
      databases, among which the studies evaluating the association of BST-1
      polymorphisms with risk of PD were used in the meta-analysis. Summary odds ratios
      (ORs) and 95% confidence intervals (CIs) were determined for different genetic
      models using meta-analytic methods. Subgroup analysis was performed based on
      study designs and participant ethnicity, and sensitivity analysis was also
      performed. Eleven studies comprising 11,070 cases and 19,169 controls were
      included in this meta-analysis. ORs and 95% CIs were used to assess the strength
      of association. The rs4698412 variant (G->A) showed a significant summary OR of
      1.12 (95% CI: 1.05-1.20; P=0.001) in an allelic model. This significant
      association was also observed in the subgroup analysis based on participants'
      ethnicity and study designs. The pooled OR of the rs11724635 variant (C->A)
      indicated a non-significant association with PD in a recessive model (OR, 1.16,
      95% CI: 0.97-1.40; P=0.112), dominant model (OR, 1.10, 95% CI: 0.86-1.41;
      P=0.458) and allelic model (OR, 1.10, 95% CI: 0.95-1.27; P=0.224). Although the
      rs11931532 variant (T->C) did not show association with PD (OR, 0.99, 95% CI:
      0.85-1.15; P=0.9), the pooled estimation of genome-wide association studies
      (GWAS) showed a significant connection with PD (OR, 1.19, 95% CI: 1.08-1.31;
      P=0.001). Sensitivity analysis supported these findings, and no evidence of
      publication bias was observed in the meta-analysis. Our studies suggested that
      the rs4698412 variant of BST-1 may increase the PD susceptibility. 

PMID- 25986900
TI  - Tracing thyroid hormone-disrupting compounds: database compilation and structure
      activity evaluation for an effect-directed analysis of sediment.
AB  - A variety of anthropogenic compounds has been found to be capable of disrupting
      the endocrine systems of organisms, in laboratory studies as well as in wildlife.
      The most widely described endpoint is estrogenicity, but other hormonal
      disturbances, e.g., thyroid hormone disruption, are gaining more and more
      attention. Here, we present a review and chemical characterization, using
      principal component analysis, of organic compounds that have been tested for
      their capacity to bind competitively to the thyroid hormone transport protein
      transthyretin (TTR). The database contains 250 individual compounds and technical
      mixtures, of which 144 compounds are defined as TTR binders. Almost one third of
      these compounds (n = 52) were even more potent than the natural hormone thyroxine
      (T4). The database was used as a tool to assist in the identification of thyroid
      hormone-disrupting compounds (THDCs) in an effect-directed analysis (EDA) study
      of a sediment sample. Two compounds could be confirmed to contribute to the
      detected TTR-binding potency in the sediment sample, i.e., triclosan and
      nonylphenol technical mixture. They constituted less than 1% of the TTR-binding
      potency of the unfractionated extract. The low rate of explained activity may be
      attributed to the challenges related to identification of unknown contaminants in
      combination with the limited knowledge about THDCs in general. This study
      demonstrates the need for databases containing compound-specific toxicological
      properties. In the framework of EDA, such a database could be used to assist in
      the identification and confirmation of causative compounds focusing on thyroid
      hormone disruption.

PMID- 25986901
TI  - Regulation of the Min Cell Division Inhibition Complex by the Rcs Phosphorelay in
      Proteus mirabilis.
AB  - A key regulator of swarming in Proteus mirabilis is the Rcs phosphorelay, which
      represses flhDC, encoding the master flagellar regulator FlhD4C2. Mutants in
      rcsB, the response regulator in the Rcs phosphorelay, hyperswarm on solid agar
      and differentiate into swarmer cells in liquid, demonstrating that this system
      also influences the expression of genes central to differentiation. To gain a
      further understanding of RcsB-regulated genes involved in swarmer cell
      differentiation, transcriptome sequencing (RNA-Seq) was used to examine the RcsB
      regulon. Among the 133 genes identified, minC and minD, encoding cell division
      inhibitors, were identified as RcsB-activated genes. A third gene, minE, was
      shown to be part of an operon with minCD. To examine minCDE regulation, the min
      promoter was identified by 5' rapid amplification of cDNA ends (5'-RACE), and
      both transcriptional lacZ fusions and quantitative real-time reverse
      transcriptase (qRT) PCR were used to confirm that the minCDE operon was RcsB
      activated. Purified RcsB was capable of directly binding the minC promoter
      region. To determine the role of RcsB-mediated activation of minCDE in swarmer
      cell differentiation, a polar minC mutation was constructed. This mutant formed
      minicells during growth in liquid, produced shortened swarmer cells during
      differentiation, and exhibited decreased swarming motility. IMPORTANCE: This work
      describes the regulation and role of the MinCDE cell division system in P.
      mirabilis swarming and swarmer cell elongation. Prior to this study, the
      mechanisms that inhibit cell division and allow swarmer cell elongation were
      unknown. In addition, this work outlines for the first time the RcsB regulon in
      P. mirabilis. Taken together, the data presented in this study begin to address
      how P. mirabilis elongates upon contact with a solid surface.

PMID- 25986902
TI  - The Protein Interactome of Mycobacteriophage Giles Predicts Functions for Unknown
      Proteins.
AB  - Mycobacteriophages are viruses that infect mycobacterial hosts and are prevalent
      in the environment. Nearly 700 mycobacteriophage genomes have been completely
      sequenced, revealing considerable diversity and genetic novelty. Here, we have
      determined the protein complement of mycobacteriophage Giles by mass spectrometry
      and mapped its genome-wide protein interactome to help elucidate the roles of its
      77 predicted proteins, 50% of which have no known function. About 22,000
      individual yeast two-hybrid (Y2H) tests with four different Y2H vectors, followed
      by filtering and retest screens, resulted in 324 reproducible protein-protein
      interactions, including 171 (136 nonredundant) high-confidence interactions. The
      complete set of high-confidence interactions among Giles proteins reveals new
      mechanistic details and predicts functions for unknown proteins. The Giles
      interactome is the first for any mycobacteriophage and one of just five known
      phage interactomes so far. Our results will help in understanding
      mycobacteriophage biology and aid in development of new genetic and therapeutic
      tools to understand Mycobacterium tuberculosis. IMPORTANCE: Mycobacterium
      tuberculosis causes over 9 million new cases of tuberculosis each year.
      Mycobacteriophages, viruses of mycobacterial hosts, hold considerable potential
      to understand phage diversity, evolution, and mycobacterial biology, aiding in
      the development of therapeutic tools to control mycobacterial infections. The
      mycobacteriophage Giles protein-protein interaction network allows us to predict
      functions for unknown proteins and shed light on major biological processes in
      phage biology. For example, Giles gp76, a protein of unknown function, is found
      to associate with phage packaging and maturation. The functions of
      mycobacteriophage-derived proteins may suggest novel therapeutic approaches for
      tuberculosis. Our ORFeome clone set of Giles proteins and the interactome data
      will be useful resources for phage interactomics.

PMID- 25986903
TI  - An SOS Regulon under Control of a Noncanonical LexA-Binding Motif in the
      Betaproteobacteria.
AB  - The SOS response is a transcriptional regulatory network governed by the LexA
      repressor that activates in response to DNA damage. In the Betaproteobacteria,
      LexA is known to target a palindromic sequence with the consensus sequence CTGT
      N8-ACAG. We report the characterization of a LexA regulon in the iron-oxidizing
      betaproteobacterium Sideroxydans lithotrophicus. In silico and in vitro analyses
      show that LexA targets six genes by recognizing a binding motif with the
      consensus sequence GAACGaaCGTTC, which is strongly reminiscent of the Bacillus
      subtilis LexA-binding motif. We confirm that the closely related Gallionella
      capsiferriformans shares the same LexA-binding motif, and in silico analyses
      indicate that this motif is also conserved in the Nitrosomonadales and the
      Methylophilales. Phylogenetic analysis of LexA and the alpha subunit of DNA
      polymerase III (DnaE) reveal that the organisms harboring this noncanonical LexA
      form a compact taxonomic cluster within the Betaproteobacteria. However, their
      lexA gene is unrelated to the standard Betaproteobacteria lexA, and there is
      evidence of its spread through lateral gene transfer. In contrast to other
      reported cases of noncanonical LexA-binding motifs, the regulon of S.
      lithotrophicus is comparable in size and function to that of many other
      Betaproteobacteria, suggesting that a convergent SOS regulon has reevolved under
      the control of a new LexA protein. Analysis of the DNA-binding domain of S.
      lithotrophicus LexA reveals little sequence similarity with that of other LexA
      proteins targeting similar binding motifs, suggesting that network structure may
      limit site evolution or that structural constrains make the B. subtilis-type
      motif an optimal interface for multiple LexA sequences. IMPORTANCE: Understanding
      the evolution of transcriptional systems enables us to address important
      questions in microbiology, such as the emergence and transfer potential of
      different regulatory systems to regulate virulence or mediate responses to
      stress. The results reported here constitute the first characterization of a
      noncanonical LexA protein regulating a standard SOS regulon. This is significant
      because it illustrates how a complex transcriptional program can be put under the
      control of a novel transcriptional regulator. Our results also reveal a
      substantial degree of plasticity in the LexA recognition domain, raising
      intriguing questions about the space of protein-DNA interfaces and the specific
      evolutionary constrains faced by these elements.

PMID- 25986904
TI  - Two Master Switch Regulators Trigger A40926 Biosynthesis in Nonomuraea sp. Strain
      ATCC 39727.
AB  - The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide
      A40926, the precursor of dalbavancin. Biosynthesis of A40926 is encoded by the
      dbv gene cluster, which contains 37 protein-coding sequences that participate in
      antibiotic biosynthesis, regulation, immunity, and export. In addition to the
      positive regulatory protein Dbv4, the A40926-biosynthetic gene cluster encodes
      two additional putative regulators, Dbv3 and Dbv6. Independent mutations in these
      genes, combined with bioassays and liquid chromatography-mass spectrometry (LC
      MS) analyses, demonstrated that Dbv3 and Dbv4 are both required for antibiotic
      production, while inactivation of dbv6 had no effect. In addition, overexpression
      of dbv3 led to higher levels of A40926 production. Transcriptional and
      quantitative reverse transcription (RT)-PCR analyses showed that Dbv4 is
      essential for the transcription of two operons, dbv14-dbv8 and dbv30-dbv35, while
      Dbv3 positively controls the expression of four monocistronic transcription units
      (dbv4, dbv29, dbv36, and dbv37) and of six operons (dbv2-dbv1, dbv14-dbv8, dbv17
      dbv15, dbv21-dbv20, dbv24-dbv28, and dbv30-dbv35). We propose a complex and
      coordinated model of regulation in which Dbv3 directly or indirectly activates
      transcription of dbv4 and controls biosynthesis of 4-hydroxyphenylglycine and the
      heptapeptide backbone, A40926 export, and some tailoring reactions (mannosylation
      and hexose oxidation), while Dbv4 directly regulates biosynthesis of 3,5
      dihydroxyphenylglycine and other tailoring reactions, including the four cross
      links, halogenation, glycosylation, and acylation. IMPORTANCE: This report
      expands knowledge of the regulatory mechanisms used to control the biosynthesis
      of the glycopeptide antibiotic A40926 in the actinomycete Nonomuraea sp. strain
      ATCC 39727. A40926 is the precursor of dalbavancin, approved for treatment of
      skin infections by Gram-positive bacteria. Therefore, understanding the
      regulation of its biosynthesis is also of industrial importance. So far, the
      regulatory mechanisms used to control two other similar glycopeptides (balhimycin
      and teicoplanin) have been elucidated, and beyond a common step, different
      clusters seem to have devised different strategies to control glycopeptide
      production. Thus, our work provides one more example of the pitfalls of deducing
      regulatory roles from bioinformatic analyses only, even when analyzing gene
      clusters directing the synthesis of structurally related compounds.

PMID- 25986905
TI  - Environmental Sensing in Actinobacteria: a Comprehensive Survey on the Signaling
      Capacity of This Phylum.
AB  - Signal transduction is an essential process that allows bacteria to sense their
      complex and ever-changing environment and adapt accordingly. Three distinct major
      types of signal-transducing proteins (STPs) can be distinguished: one-component
      systems (1CSs), two-component systems (2CSs), and extracytoplasmic-function sigma
      factors (ECFs). Since Actinobacteria are particularly rich in STPs, we
      comprehensively investigated the abundance and diversity of STPs encoded in 119
      actinobacterial genomes, based on the data stored in the Microbial Signal
      Transduction (MiST) database. Overall, we observed an approximately linear
      correlation between the genome size and the total number of encoded STPs. About
      half of all membrane-anchored 1CSs are protein kinases. For both 1CSs and 2CSs, a
      detailed analysis of the domain architectures identified novel proteins that are
      found only in actinobacterial genomes. Many actinobacterial genomes are
      particularly enriched for ECFs. As a result of this study, almost 500 previously
      unclassified ECFs could be classified into 18 new ECF groups. This comprehensive
      survey demonstrates that actinobacterial genomes encode previously unknown STPs,
      which may represent new mechanisms of signal transduction and regulation. This
      information not only expands our knowledge of the diversity of bacterial signal
      transduction but also provides clear and testable hypotheses about their
      mechanisms, which can serve as starting points for experimental studies.
      IMPORTANCE: In the wake of the genomic era, with its enormous increase in the
      amount of available sequence information, the challenge has now shifted toward
      making sense and use of this treasure chest. Such analyses are a prerequisite to
      provide meaningful information that can help guide subsequent experimental
      efforts, such as mechanistic studies on novel signaling strategies. This work
      provides a comprehensive analysis of signal transduction proteins from 119
      actinobacterial genomes. We identify, classify, and describe numerous novel and
      conserved signaling devices. Hence, our work serves as an important resource for
      any researcher interested in signal transduction of this important bacterial
      phylum, which contains organisms of ecological, biotechnological, and medical
      relevance.

PMID- 25986906
TI  - Biochemical Characterization of Mycobacterium smegmatis RnhC (MSMEG_4305), a
      Bifunctional Enzyme Composed of Autonomous N-Terminal Type I RNase H and C
      Terminal Acid Phosphatase Domains.
AB  - Mycobacterium smegmatis encodes several DNA repair polymerases that are adept at
      incorporating ribonucleotides, which raises questions about how ribonucleotides
      in DNA are sensed and removed. RNase H enzymes, of which M. smegmatis encodes
      four, are strong candidates for a surveillance role. Here, we interrogate the
      biochemical activity and nucleic acid substrate specificity of M. smegmatis RnhC,
      a bifunctional RNase H and acid phosphatase. We report that (i) the RnhC nuclease
      is stringently specific for RNA:DNA hybrid duplexes; (ii) RnhC does not
      selectively recognize and cleave DNA-RNA or RNA-DNA junctions in duplex nucleic
      acid; (iii) RnhC cannot incise an embedded monoribonucleotide or diribonucleotide
      in duplex DNA; (iv) RnhC can incise tracts of 4 or more ribonucleotides embedded
      in duplex DNA, leaving two or more residual ribonucleotides at the cleaved 3'-OH
      end and at least one or two ribonucleotides on the 5'-PO4 end; (v) the RNase H
      activity is inherent in an autonomous 140-amino-acid (aa) N-terminal domain of
      RnhC; and (vi) the C-terminal 211-aa domain of RnhC is an autonomous acid
      phosphatase. The cleavage specificity of RnhC is clearly distinct from that of
      Escherichia coli RNase H2, which selectively incises at an RNA-DNA junction.
      Thus, we classify RnhC as a type I RNase H. The properties of RnhC are consistent
      with a role in Okazaki fragment RNA primer removal or in surveillance of
      oligoribonucleotide tracts embedded in DNA but not in excision repair of single
      misincorporated ribonucleotides. IMPORTANCE: RNase H enzymes help cleanse the
      genome of ribonucleotides that are present either as ribotracts (e.g., RNA
      primers) or as single ribonucleotides embedded in duplex DNA. Mycobacterium
      smegmatis encodes four RNase H proteins, including RnhC, which is characterized
      in this study. The nucleic acid substrate and cleavage site specificities of RnhC
      are consistent with a role in initiating the removal of ribotracts but not in
      single-ribonucleotide surveillance. RnhC has a C-terminal acid phosphatase domain
      that is functionally autonomous of its N-terminal RNase H catalytic domain. RnhC
      homologs are prevalent in Actinobacteria.

PMID- 25986908
TI  - Validation of the Community Integration Questionnaire in the adult burn injury
      population.
AB  - PURPOSE: With improved survival, long-term effects of burn injuries on quality of
      life, particularly community integration, are important outcomes. This study aims
      to assess the Community Integration Questionnaire's psychometric properties in
      the adult burn population. METHODS: Data were obtained from a multicenter
      longitudinal data set of burn survivors. The psychometric properties of the
      Community Integration Questionnaire (n = 492) were examined. The questionnaire
      items were evaluated for clinical and substantive relevance; validation
      procedures were conducted on different samples of the population; construct
      validity was assessed using exploratory factor analysis; internal consistency
      reliability was examined using Cronbach's alpha statistics; and item response
      theory was applied to the final models. RESULTS: The CIQ-15 was reduced by two
      questions to form the CIQ-13, with a two-factor structure, interpreted as
      self/family care and social integration. Item response theory testing suggests
      that Factor 2 captures a wider range of community integration levels. Cronbach's
      alpha was 0.80 for Factor 1, 0.77 for Factor 2, and 0.79 for the test as a whole.
      CONCLUSIONS: The CIQ-13 demonstrates validity and reliability in the adult burn
      survivor population addressing issues of self/family care and social integration.
      This instrument is useful in future research of community reintegration outcomes
      in the burn population.

PMID- 25986909
TI  - Tigecycline for carbapenem-resistant Klebsiella pneumoniae infections in the
      intensive care unit.

PMID- 25986907
TI  - Complex coevolution of depression and health-related quality of life in old age.
AB  - PURPOSE: To investigate the coevolution of depression and health-related quality
      of life (HRQoL) in old age. METHODS: In a representative survey of the German
      general population aged 75 years and older, the course of HRQoL and depression
      was observed over 4.5 years (3 waves). HRQoL was assessed by the Visual Analogue
      Scale (EQ VAS) of the EQ-5D instrument, while the Geriatric Depression Scale was
      used to measure depression. A panel vector autoregressive model was used to
      account for the complex coevolution of depression and HRQoL. Unobserved
      heterogeneity was taken into account by taking the first differences. RESULTS: We
      revealed a robust negative association between an initial change in HRQoL and a
      subsequent change in depression score, with substantial sex differences: In women
      there was a robust association, while in men the significance of this association
      depended on the model specification. Surprisingly, in the total sample and in
      both sexes, no robust association between an initial increase in depression and a
      subsequent change in HRQoL was found. CONCLUSION: Findings indicate that the
      direction of evolution from HRQoL to depression deserves more attention.
      Furthermore, treatment of depression in late life should aim at improving HRQoL
      in which remission of depressive symptoms is necessary but not sufficient.

PMID- 25986910
TI  - Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization :
      Fifty Years of Revascularization: Where Are We and Where Are We Heading?
AB  - The joint European Society of Cardiology and European Association of Cardio
      Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect
      and summarize the evidence regarding decision-making, diagnostics, and
      therapeutics in various clinical scenarios of coronary artery disease, including
      elective, urgent, and emergency settings. The 2014 document updates and extends
      the effort started in 2010, year of the first edition of these guidelines.
      Importantly, this latest edition provides a systematic review of all randomized
      clinical trials performed since 1980, comparing different strategies of
      myocardial revascularization, including coronary artery bypass graft (CABG),
      balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal
      stents (BMS) and first- and second-generation drug-eluting stents (DES). This
      review aims to highlight the most relevant novelties introduced by the 2014
      edition of the ESC/EACTS myocardial revascularization guidelines as compared with
      the previous edition and to describe similarities and differences with the
      American societies' guidelines. 

PMID- 25986911
TI  - Role of therapeutic plasmapheresis in ANCA-associated vasculitis.
AB  - Plasma exchange, or plasmapheresis, is a treatment method that developed over a
      period of two decades and involves the removal and replacement of a patient's
      circulating plasma. The aim of treatment is to remove disease-associated
      molecules and therefore interrupt disease progression. This article summarizes
      the developmental history of this treatment and then looks in more detail at data
      on the use of plasma exchange in treating antineutrophil antibody (ANCA)
      associated vasculitis. The eight randomized trials and the Cochrane Systematic
      Review on treating renal vasculitis are summarized to show that plasma exchange
      may be effective in this disease, specifically in reducing the development of end
      stage kidney disease (ESKD) by approximately 40%. The plasma exchange and
      glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody
      associated vasculitis (PEXIVAS) study is a currently enrolling study aiming to
      answer some of the outstanding questions relating to the use of this treatment in
      ANCA-associated vasculitis.

PMID- 25986912
TI  - Successful therapy of C3Nef-positive C3 glomerulopathy with plasma therapy and
      immunosuppression.
AB  - BACKGROUND: C3 glomerulopathies (C3G) are characterized by uncontrolled
      activation of the alternative pathway of complement. In most patients these
      diseases progress towards end-stage renal disease, and the risk of recurrence
      after renal transplantation is high. In the majority of patients, only antibodies
      against the C3 convertase, termed C3Nef, can be found as a potential pathogenic
      factor. Although a large variety of therapeutic approaches have been used, no
      generally accepted therapy exists. METHODS: In four consecutive patients with C3G
      in whom all known complement factor mutations were excluded and only C3Nef could
      be identified as a potential cause of disease, a multimodal therapeutic regimen
      with plasma therapy, corticosteroids and mycophenolate mofetil was used. RESULTS:
      The multimodal regimen achieved normalization of renal function in all four
      patients, with complete remission in two patients and a distinct reduction of
      proteinuria in the other two patients. The single patient with C3
      glomerulonephritis (C3GN) and marked terminal complement complex elevation only
      showed partial remission; further improvement was achieved following the addition
      of eculizumab to the therapeutic regimen. Repeatedly measured C3Nef levels did
      not correlate with disease course or therapeutic response in any of the patients.
      CONCLUSIONS: As this multimodal therapeutic approach was effective in all four
      treated patients with suspected autoimmune etiology of C3G, it offers a treatment
      option for severely affected patients with this rare disease until more specific
      regimens are available.

PMID- 25986913
TI  - Confirmation of the absence of tetrodotoxin and its analogues in the juveniles of
      the Japanese fire-bellied newt, Cynops pyrrhogaster, captive-reared from eggs in
      the laboratory using HILIC-LC-MS.
AB  - The tetrodotoxin (TTX) contents of the Japanese fire-bellied newt, Cynops
      pyrrhogaster, captive-reared from eggs to metamorphosed juveniles with a non
      toxic diet for 70 weeks, as well as wild-caught juvenile newts, were investigated
      using a high-resolution hydrophilic interaction chromatography-LC-MS. TTX was
      detected in 0- to 22-week-old captive-reared juvenile newts but was not detected
      (<15 ng/g) in the 36- to 70-week-old newts, while significant levels of TTX (1.3
      14 MUg/g) were detected in the wild-caught juveniles. 

PMID- 25986916
TI  - [Neuro-oncology].

PMID- 25986914
TI  - High-throughput transcriptomic analysis nominates proteasomal genes as age
      specific biomarkers and therapeutic targets in prostate cancer.
AB  - BACKGROUND: Although prostate cancer (PCa) is hypothesized to differ in nature
      between younger versus older patients, the underlying molecular distinctions are
      poorly understood. We hypothesized that high-throughput transcriptomic analysis
      would elucidate biological differences in PCas arising in younger versus older
      men, and would nominate potential age-specific biomarkers and therapeutic
      targets. METHODS: The high-density Affymetrix GeneChip platform, encompassing >1
      million genomic loci, was utilized to assess gene expression in 1090 radical
      prostatectomy samples from patients with long-term follow-up. We identified genes
      associated with metastatic progression by 10 years post-treatment in younger
      (age<65) versus older (age?65) patients, and ranked these genes by their
      prognostic value. We performed Gene Set Enrichment Analysis (GSEA) to nominate
      biological concepts that demonstrated age-specific effects, and validated a
      target by treating with a clinically available drug in three PCa cell lines
      derived from younger men. RESULTS: Over 80% of the top 1000 prognostic genes in
      younger and older men were specific to that age group. GSEA nominated the
      proteasome pathway as the most differentially prognostic in younger versus older
      patients. High expression of proteasomal genes conferred worse prognosis in
      younger but not older men on univariate and multivariate analysis. Bortezomib, a
      Food and Drug Administration approved proteasome inhibitor, decreased
      proliferation in three PCa cell lines derived from younger patients. CONCLUSIONS:
      Our data show significant global differences in prognostic genes between older
      versus younger men. We nominate proteasomeal gene expression as an age-specific
      biomarker and potential therapeutic target specifically in younger men.
      Limitations of our study include clinical differences between cohorts, and
      increased comorbidities and lower survival in older patients. These intriguing
      findings suggest that current models of PCa biology do not adequately represent
      genetic heterogeneity of PCa related to age, and future clinical trials would
      benefit from stratification based on age.

PMID- 25986915
TI  - Magnetic resonance imaging on disease reclassification among active surveillance
      candidates with low-risk prostate cancer: a diagnostic meta-analysis.
AB  - BACKGROUND: Active surveillance (AS) is an increasingly important attempt to
      avoid overtreatment of patients who harbor clinically insignificant disease while
      offering curative treatment to those in whom disease is reclassified as higher
      risk after an observation period and repeat biopsy. We aim to evaluate the
      diagnostic performance of magnetic resonance imaging (MRI) in predicting
      upgrading on confirmatory biopsy in men with low-risk prostate cancer (PCa) on
      AS. METHODS: We searched the PubMed for pertinent studies up to November 2014. We
      used standard methods recommended for meta-analyses of diagnostic test
      evaluations. The analysis was based on a summary receiver operating
      characteristic (SROC) curve. Meta-regression analysis was used to assess the
      effects of some confounding factors on the results of the meta-analysis. The
      potential presence of publication bias was tested using the Deeks' funnel plots.
      RESULTS: Seven studies provided the diagnostic data on MRI and AS of PCa,
      comprising 1028 patients. The pooled estimates of MRI on disease reclassification
      among AS candidates were as follows: sensitivity, 0.69 (95% confidence interval
      (CI), 0.44-0.86); specificity, 0.78 (95% CI, 0.53-0.91); positive likelihood
      ratio, 3.1 (95% CI, 1.6-6.0); negative likelihood ratio, 0.40 (95% CI, 0.23
      0.70); and diagnostic odds ratio, 8 (95% CI, 4-16). The P-value for heterogeneity
      was <0.001. We found that the SROC curve is positioned toward the desirable upper
      left corner of the curve, and the area under the curve was 0.79 (95% CI, 0.76
      0.83). For a pretest probability of 0.20, the corresponding positive predictive
      value (PPV) was 0.44 and the negative predictive value (NPV) was 0.91. MRI may
      reveal an unrecognized significant lesion in 33.27% of patients, and biopsy of
      these areas reclassified 14.59% of cases as no longer fulfilling the criteria for
      AS. In addition, when no suspicious disease progression (66.34%) was identified
      on MRI, the chance of reclassification on repeat biopsy was extremely low at
      6.13%. CONCLUSIONS: MRI, especially multiparametric (MP)-MRI, has a moderate
      diagnostic accuracy as a significant predictor of disease reclassification among
      AS candidates. The high NPV and specificity for the prediction of biopsy
      reclassification upon clinical follow-up suggest that negative prostate MRI
      findings may support a patient remaining under AS. Although the PPV and
      sensitivity for the prediction were relatively low, the presence of a suspicious
      lesion >10 mm lesion may suggest an increased risk for disease progression.

PMID- 25986917
TI  - Interplay between patient global assessment, pain, and fatigue and influence of
      other clinical disease activity measures in patients with active rheumatoid
      arthritis.
AB  - The interplay between patient-reported outcome measures in rheumatology is not
      well clarified. The objective of the study was to examine associations on the
      group level and concordance on the individual patient level between patient
      global assessment (PaGl), pain, and fatigue as scored on visual analog scales
      (VAS) in the daily clinic by patients with active rheumatoid arthritis (RA).
      Associations with other measures of disease activity were also examined.
      Traditional disease activity data on 221 RA patients with active disease planned
      to initiate biological treatment were extracted from the Danish DANBIO registry.
      Associations between VAS PaGl, pain, and fatigue (0-100) were examined using
      multiple regression analysis. Concordance between the VAS scores was expressed as
      the bias (mean difference between intra-individual scores) and the 95% lower and
      upper limits of agreement (LLoA; ULoA) according to the Bland-Altman method. Mean
      age was 57 +/- 14 years, mean Disease Activity Score (DAS28-CRP4) 5.0 +/- 0.9,
      and mean PaGl 63.6 +/- 22.6. PaGl was most strongly predicted by pain and
      fatigue, pain by PaGl and fatigue, and fatigue by PaGl and pain (beta ranging
      from 0.17 to 0.69, p < 0.01-0.0001). More objective measures were not or far less
      predictive. LLoA;ULoA [bias] for PaGl vs. pain was -19.1; 29.5 [5.2], for PaGl
      vs. fatigue -22.8; 28.6 [2.9], and for fatigue vs. pain -29.2; 33.8 [2.3]. In
      conclusion, PaGl, pain, and fatigue were most strongly explained by each other,
      not by more objective clinical measures of disease activity and were nearly
      identical on the group level. On the individual patient level, however,
      differences between the scores varied considerably. The findings highlight the
      challenge of understanding and dealing with traditional patient-reported VAS
      measures when it comes to individual RA patients in the daily clinic.

PMID- 25986918
TI  - 'Whom will I give him to? The difficulty is mine' : Psychosocial difficulties
      experienced by care givers of patients with epilepsy in Cape Town, South Africa.
AB  - Epilepsy has been reported as one condition that can cause psychological
      difficulties and distress to care givers of patients suffering from the
      condition. This study explored psychological difficulties experienced by lay care
      givers of patients with epilepsy in an urban township in South Africa. Nine
      individual in-depth interviews were conducted with lay carers who provide care to
      their relatives, friends and neighbours who have epilepsy. A thematic data
      analysis method was used. Some fears, social concerns and worries affecting care
      giving were reported. Community interventions that promote cultural sensitivity
      in mental health care and empowerment of these carers are needed.

PMID- 25986919
TI  - Self-efficacy mediates the relationship of depressive symptoms and social support
      with adherence in patients with heart failure.
AB  - Poor self-care is common among adults with heart failure and leads to poor health
      outcomes. Low self-efficacy, depression, and low social support are associated
      with poor self-care, but knowledge about these relationships in heart failure is
      limited. Secondary data analysis of cross-sectional data from 346 adults with
      heart failure measuring self-efficacy, depressive symptoms, social support, and
      self-care adherence was conducted. Tests of mediation using multiple linear
      regressions indicate that self-efficacy fully mediates the relationships between
      depression and adherence, and social support and adherence. Bolstering self
      efficacy may have a greater impact on self-care adherence than targeting either
      depression or social support alone.

PMID- 25986920
TI  - Longitudinal association between depressive symptoms and walking impairment in
      people with relapsing-remitting multiple sclerosis.
AB  - Worsening depressive symptoms and walking impairment are significant burdens in
      multiple sclerosis. We explored the reciprocal relationship between depressive
      symptoms and walking impairment in a cohort of 269 people with relapsing
      remitting multiple sclerosis over 2 years. The data were examined using
      longitudinal panel analysis in Mplus. Baseline depressive symptoms predicted
      change in walking impairment at 1-year follow-up (path coefficient = .074), and
      change in walking impairment at 1-year follow-up predicted change in depressive
      symptoms at 2-year follow-up (path coefficient = .177). Our study provides
      preliminary evidence for initiation of a reciprocal relationship between
      depressive symptoms and walking impairment in relapsing-remitting multiple
      sclerosis.

PMID- 25986921
TI  - Designing Two-Dimensional Protein Arrays through Fusion of Multimers and
      Interface Mutations.
AB  - We have combined fusion of oligomers with cyclic symmetry and alanine
      substitutions to eliminate clashes and produce proteins that self-assemble into 2
      D arrays upon addition of calcium ions. Using TEM, AFM, small-angle X-ray
      scattering, and fluorescence microscopy, we show that the designed lattices which
      are 5 nm high with p3 space group symmetry and 7.25 nm periodicity self-assemble
      into structures that can exceed 100 MUm in characteristic length. The versatile
      strategy, experimental approach, and hexagonal arrays described herein should
      prove valuable for the engineering of functional nanostructured materials in 2-D.

PMID- 25986922
TI  - International society for gastrointestinal hereditary tumours-InSiGHT.

PMID- 25986924
TI  - Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related
      increase of Plzf expression.
AB  - Like stem cells in other tissues, spermatogonia, including spermatogonial stem
      cells (SSCs) at the foundation of differentiation hierarchy, undergo age-related
      decline in function. The promyelocytic leukemia zinc finger (Plzf) protein plays
      an essential role in spermatogonia maintenance by preventing their
      differentiation. To evaluate whether there is an age-related change in Plzf
      expression, we found that aged mouse testes exhibited a robust "Plzf
      overexpression" phenotype, in that they showed not only a higher frequency of
      Plzf-expressing cells but also an increased level of Plzf expression in these
      cells. Moreover, some Plzf-expressing cells in aged testes even aberrantly
      appeared in the differentiating spermatogonia compartment, which is usually low
      or negative for Plzf expression. Importantly, ectopic Plzf expression in F9 cells
      suppressed retinoic acid (RA)-induced Stra8 activation, a gene required for
      meiosis initiation. These data, together with our observation of a lack of
      meiosis-initiating spermatocytes associated with high Plzf-expressing
      spermatogonia in the aged testes, particularly in the degenerative seminiferous
      tubules, suggest that age-related increase in Plzf expression represents a novel
      molecular signature of spermatogonia aging by functionally arresting their
      differentiation.

PMID- 25986926
TI  - From multi-responsive tri- and diblock copolymers to diblock-copolymer-decorated
      gold nanoparticles: the effect of architecture on micellization behaviors in
      aqueous solutions.
AB  - This work reports on the aqueous stimuli-responsive behaviors of an ABA triblock
      copolymer, a BAB triblock copolymer, an AB diblock copolymer and citrate-based
      gold nanoparticles decorated with AB diblock copolymers (where A is the pH- and
      thermo-responsive poly[N,N-(dimethylamino)ethyl methacrylate] (PDMAEMA) and B is
      the thermo-responsive poly[2-(2-methoxyethoxy)ethyl methacrylate] (PMEO2MA)). The
      symmetric triblock polymers were synthesized via sequential atom transfer radical
      polymerization (ATRP) using a disulfide-functionalized initiator. Subsequently,
      the thiol-ended diblock copolymers were facilely obtained by reducing these
      triblock copolymers and were grafted onto gold nanoparticle (AuNP) surfaces via
      ligand exchange to yield stimuli-sensitive gold nanoparticles (Au@AB and Au@BA).
      The ABA and BAB triblock copolymers exhibited two-step thermo-induced aggregation
      behavior in water at a pH near the isoelectric point (IEP), which resulted in the
      formation of micelles after the first lower critical solution temperature (LCST)
      and large aggregates consisting of clustered micelles above the second LCST
      transition. The significant difference between the micelle sizes of the ABA and
      BAB copolymers, such that the micelle size of the BAB copolymer was smaller than
      that of the ABA copolymer although both had a similar unit composition, suggests
      a distinction between the micelle structures. The "branch" and "flower-like"
      micelles that are formed in the ABA and BAB aqueous solutions, respectively,
      ultimately governed the phase transition behaviors. The AB diblock copolymer
      exhibited similar micellization behavior and a micelle size roughly similar to
      that of the ABA triblock copolymer, although the chain length of the AB copolymer
      is only half that of the ABA copolymer. Both Au@PDMAEMA-PMEO2MA and Au@PMEO2MA
      PDMAEMA showed similar dual LCST behaviors and pH-responsive behaviors in aqueous
      solutions without the addition of salt. A significant difference was observed
      between the two types of hybrid AuNPs in salty solutions, in which only the
      Au@PDMAEMA-PMEO2MA system exhibited thermo-induced aggregation behavior. These
      hybrid nanoparticles can be used as phase transfer reagents. Additionally, AuNPs
      capped with PDMAEMA-PMEO2MA diblock copolymer can spontaneously transfer across a
      water-toluene interface. 

PMID- 25986925
TI  - Dynamic treatment effect (DTE) curves reveal the mode of action for standard and
      experimental cancer therapies.
AB  - We present a method for estimating the empirical dynamic treatment effect (DTE)
      curves from tumor growth delay (TGD) studies. This improves on current common
      methods of TGD analysis, such as T/C ratio and doubling times, by providing a
      more detailed treatment effect and overcomes their lack of reproducibility. The
      methodology doesn't presuppose any prior form for the treatment effect dynamics
      and is shown to give consistent estimates with missing data. The method is
      illustrated by application to real data from TGD studies involving three types of
      therapy. Firstly, we demonstrate that radiotherapy induces a sharp peak in
      inhibition in a FaDu model. The height, duration and timing of the peak increase
      linearly with radiation dose. Second, we demonstrate that a combination of
      temozolomide and an experimental therapy in a glioma PDX model yields an effect,
      similar to an additive version of the DTE curves for the mono-therapies, except
      that there is a 30 day delay in peak inhibition. In the third study, we consider
      the DTE of anti-angiogenic therapy in glioma. We show that resulting DTE curves
      are flat. We discuss how features of the DTE curves should be interpreted and
      potentially used to improve therapy. 

PMID- 25986923
TI  - EMT, CTCs and CSCs in tumor relapse and drug-resistance.
AB  - Tumor relapse and metastasis are the primary causes of poor survival rates in
      patients with advanced cancer despite successful resection or chemotherapeutic
      treatment. A primary cause of relapse and metastasis is the persistence of cancer
      stem cells (CSCs), which are highly resistant to chemotherapy. Although highly
      efficacious drugs suppressing several subpopulations of CSCs in various tissue
      specific cancers are available, recurrence is still common in patients. To find
      more suitable therapy for relapse, the mechanisms underlying metastasis and drug
      resistance associated with relapse-initiating CSCs need to be identified. Recent
      studies in circulating tumor cells (CTCs) of some cancer patients manifest
      phenotypes of both CSCs and epithelial-mesenchymal transition (EMT). These
      patients are unresponsive to standard chemotherapies and have low progression
      free survival, suggesting that EMT-positive CTCs are related to co-occur with or
      transform into relapse-initiating CSCs. Furthermore, EMT programming in cancer
      cells enables in the remodeling of extracellular matrix to break the dormancy of
      relapse-initiating CSCs. In this review, we extensively discuss the association
      of the EMT program with CTCs and CSCs to characterize a subpopulation of patients
      prone to relapses. Identifying the mechanisms by which EMT-transformed CTCs and
      CSCs initiate relapse could facilitate the development of new or enhanced
      personalized therapeutic regimens. 

PMID- 25986927
TI  - Complete genome of a coastal marine bacterium Muricauda lutaonensis KCTC
      22339(T).
AB  - Muricauda lutaonensis KCTC 22339(T) is a yellow-pigmented, gram-negative, rod
      shaped bacterium that was isolated from a coastal hot spring of a volcanic island
      in the Pacific Ocean, off the eastern coast of Taiwan. We here report the
      complete genome of M. lutaonensis KCTC 22339(T), which consists of 3,274,259bp
      with the G+C content of 44.97%. The completion of the M. lutaonensis genome
      sequence is expected to provide a valuable resource for understanding the
      secondary metabolic pathways related to bacterial pigmentation. 

PMID- 25986928
TI  - Mechanoelectrochemical catalysis of the effect of elastic strain on a platinum
      nanofilm for the ORR exerted by a shape memory alloy substrate.
AB  - Both the ligand effect and surface strain can affect the electrocatalytic
      reactivity. In that matter exists a need to be fundamentally understood; however,
      there is no effective strategy to isolate the strain effect in electrocatalytic
      systems. In this research we show how the elastic strain in a platinum nanofilm
      varies the catalytic activity for the oxygen reduction reaction, a key barrier to
      the wide applications of fuel cells. NiTi shape memory alloy was selected as the
      substrate to strain engineer the deposited Pt nanofilm in both compressively and
      tensilely strained states by taking advantage of the two-way shape memory effect
      for the first time. We demonstrate that compressive strain weakens the Pt surface
      adsorption and hence improves the ORR activity, which reflects in a 52%
      enhancement of the kinetic rate constant and a 27 mV positive shift of the half
      wave potential for the compressively strained 5 nm Pt compared to the pristine
      Pt. Tensile strain has the opposite effect, which is in general agreement with
      the proposed d-band theory. 

PMID- 25986929
TI  - CORR Insights((r)): Anterior and Anterolateral Approaches for THA Are Associated
      With Lower Dislocation Risk Without Higher Revision Risk.

PMID- 25986931
TI  - A comprehensive analysis of phosphatase and tensin homolog deleted on chromosome
      10 (PTEN) loss in colorectal cancer.
AB  - BACKGROUND: Alterations of PTEN, regulator of the PTEN/PI3K-AKT pathway, are
      common in several types of cancer. This study aimed to do comprehensive analysis
      of PTEN in colorectal cancer patients. METHODS: Totally, 198 colorectal cancer
      patients who received surgery at Taipei Veterans General Hospital from 2006 to
      2008 were enrolled. Mutations, loss of protein expression, promoter
      hypermethylation, and DNA copy number of PTEN were analyzed by sequencing,
      immunohistochemistry, methylation-specific polymerase chain reaction PCR, and
      quantitative (QPCR), respectively, and correlated with clinicopathological
      features and patients' outcome. RESULTS: Genomic mutations, loss of protein
      expression, promoter hypermethylation, and decreased DNA copy number of PTEN were
      found in 4 (2.02 %), 68 (34.3 %), 54 (27.3 %), and 36 (18.2 %) tumors,
      respectively. Of these 68 tumors with loss expression of PTEN, 34 (50 %) tumors
      had promoter methylation and 18 (26.5 %) had decreased DNA copy number. All four
      tumors with PTEN mutations demonstrated loss of PTEN expression. In the stage I
      disease, frequency of loss of PTEN expression was 20 % and significantly
      increased to 56.9 % in stage IV disease. Either loss expression of PTEN, PTEN
      hypermethylation or decreased PTEN copy number was not associated with colorectal
      cancer (CRC) patients' outcome. CONCLUSIONS: PTEN alterations were found in up to
      one-third of colorectal cancers but did not impact CRC patients' prognosis.

PMID- 25986930
TI  - Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced
      pulmonary fibrosis.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal
      lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a
      novel approach with great therapeutic potential for the treatment of lung
      diseases. Despite demonstration of MSC grafting, the populations of engrafted
      MSCs have been shown to decrease dramatically 24 hours post-transplantation due
      to exposure to harsh microenvironments. Hypoxia is known to induce expression of
      cytoprotective genes and also secretion of anti-inflammatory, anti-apoptotic and
      anti-fibrotic factors. Hypoxic preconditioning is thought to enhance the
      therapeutic potency and duration of survival of engrafted MSCs. In this work, we
      aimed to prolong the duration of survival of engrafted MSCs and to enhance the
      effectiveness of idiopathic pulmonary fibrosis transplantation therapy by the use
      of hypoxia-preconditioned MSCs. METHODS: Hypoxic preconditioning was achieved in
      MSCs under an optimal hypoxic environment. The expression levels of
      cytoprotective factors and their biological effects on damaged alveolar
      epithelial cells or transforming growth factor-beta 1-treated fibroblast cells
      were studied in co-culture experiments in vitro. Furthermore, hypoxia
      preconditioned MSCs (HP-MSCs) were intratracheally instilled into bleomycin
      induced pulmonary fibrosis mice at day 3, and lung functions, cellular, molecular
      and pathological changes were assessed at 7 and 21 days after bleomycin
      administration. RESULTS: The expression of genes for pro-survival, anti
      apoptotic, anti-oxidant and growth factors was upregulated in MSCs under hypoxic
      conditions. In transforming growth factor-beta 1-treated MRC-5 fibroblast cells,
      hypoxia-preconditioned MSCs attenuated extracellular matrix production through
      paracrine effects. The pulmonary respiratory functions significantly improved for
      up to 18 days of hypoxia-preconditioned MSC treatment. Expression of inflammatory
      factors and fibrotic factor were all downregulated in the lung tissues of the
      hypoxia-preconditioned MSC-treated mice. Histopathologic examination observed a
      significant amelioration of the lung fibrosis. Several LacZ-labeled MSCs were
      observed within the lungs in the hypoxia-preconditioned MSC treatment groups at
      day 21, but no signals were detected in the normoxic MSC group. Our data further
      demonstrated that upregulation of hepatocyte growth factor possibly played an
      important role in mediating the therapeutic effects of transplanted hypoxia
      preconditioned MSCs. CONCLUSION: Transplantation of hypoxia-preconditioned MSCs
      exerted better therapeutic effects in bleomycin-induced pulmonary fibrotic mice
      and enhanced the survival rate of engrafted MSCs, partially due to the
      upregulation of hepatocyte growth factor.

PMID- 25986932
TI  - A review of the efficacy of dietary polyphenols in experimental models of
      inflammatory bowel diseases.
AB  - Crohn's disease and ulcerative colitis presently have no cure and are treated
      with anti-inflammatory drugs or monoclonal antibodies targeting pro-inflammatory
      cytokines. A variety of rodent models have been used to model chronic and acute
      colitis. Dietary polyphenols in foods and botanicals are of considerable interest
      for prevention and treatment of colitis. Many dietary polyphenols have been
      utilized for prevention of colitis in rodent models. Berries, green tea
      polyphenols, curcumin, and stilbenes have been the most extensively tested
      polyphenols in rodent models of colitis. The majority of polyphenols tested have
      inhibited colitis in rodents, but increasing doses of EGCG and green tea,
      isoflavones, flaxseed, and alpha-mangostin have exacerbated colitis. Few studies
      have examined combination of polyphenols or other bioactives for inhibition of
      colitis. Translating polyphenol doses used in rodent models of colitis to human
      equivalent doses reveals that supplemental doses are most likely required to
      inhibit colitis from a single polyphenol treatment. The ability to translate
      polyphenol treatments in rodent models is likely to be limited by species
      differences in xenobiotic metabolism and microbiota. Given these limitations,
      data from polyphenols in rodent models suggests merit for pursuing additional
      clinical studies for prevention of colitis.

PMID- 25986933
TI  - Reply to the Letter to the Editor: "Chest physiotherapy effectiveness to reduce
      hospitalization and mechanical ventilation length of stay, pulmonary infection
      rate and mortality in ICU patients".

PMID- 25986935
TI  - Bayesian inference of reaction kinetics from single-cell recordings across a
      heterogeneous cell population.
AB  - Single-cell experimental techniques provide informative data to help uncover
      dynamical processes inside a cell. Making full use of such data requires
      dedicated computational methods to estimate biophysical process parameters and
      states in a model-based manner. In particular, the treatment of heterogeneity or
      cell-to-cell variability deserves special attention. The present article provides
      an introduction to one particular class of algorithms which employ
      marginalization in order to take heterogeneity into account. An overview of
      alternative approaches is provided for comparison. We treat two frequently
      encountered scenarios in single-cell experiments, namely, single-cell trajectory
      data and single-cell distribution data. 

PMID- 25986934
TI  - Protein structure prediction guided by crosslinking restraints--A systematic
      evaluation of the impact of the crosslinking spacer length.
AB  - Recent development of high-resolution mass spectrometry (MS) instruments enables
      chemical crosslinking (XL) to become a high-throughput method for obtaining
      structural information about proteins. Restraints derived from XL-MS experiments
      have been used successfully for structure refinement and protein-protein docking.
      However, one formidable question is under which circumstances XL-MS data might be
      sufficient to determine a protein's tertiary structure de novo? Answering this
      question will not only include understanding the impact of XL-MS data on sampling
      and scoring within a de novo protein structure prediction algorithm, it must also
      determine an optimal crosslinker type and length for protein structure
      determination. While a longer crosslinker will yield more restraints, the value
      of each restraint for protein structure prediction decreases as the restraint is
      consistent with a larger conformational space. In this study, the number of
      crosslinks and their discriminative power was systematically analyzed in silico
      on a set of 2055 non-redundant protein folds considering Lys-Lys, Lys-Asp, Lys
      Glu, Cys-Cys, and Arg-Arg reactive crosslinkers between 1 and 60A. Depending on
      the protein size a heuristic was developed that determines the optimal
      crosslinker length. Next, simulated restraints of variable length were used to de
      novo predict the tertiary structure of fifteen proteins using the BCL::Fold
      algorithm. The results demonstrate that a distinct crosslinker length exists for
      which information content for de novo protein structure prediction is maximized.
      The sampling accuracy improves on average by 1.0 A and up to 2.2 A in the most
      prominent example. XL-MS restraints enable consistently an improved selection of
      native-like models with an average enrichment of 2.1.

PMID- 25986936
TI  - Informatic deconvolution of biased GPCR signaling mechanisms from in vivo
      pharmacological experimentation.
AB  - Ligands possessing different physico-chemical structures productively interact
      with G protein-coupled receptors generating distinct downstream signaling events
      due to their abilities to activate/select idiosyncratic receptor entities
      ('receptorsomes') from the full spectrum of potential receptor partners. We have
      employed multiple novel informatic approaches to identify and characterize the in
      vivo transcriptomic signature of an arrestin-signaling biased ligand, [D
      Trp(12),Tyr(34)]-bPTH(7-34), acting at the parathyroid hormone type 1 receptor
      (PTH1R), across six different murine tissues after chronic drug exposure. We are
      able to demonstrate that [D-Trp(12),Tyr(34)]-bPTH(7-34) elicits a distinctive
      arrestin-signaling focused transcriptomic response that is more coherently
      regulated, in an arrestin signaling-dependent manner, across more tissues than
      that of the pluripotent endogenous PTH1R ligand, hPTH(1-34). This arrestin
      focused response signature is strongly linked with the transcriptional regulation
      of cell growth and development. Our informatic deconvolution of a conserved
      arrestin-dependent transcriptomic signature from wild type mice demonstrates a
      conceptual framework within which the in vivo outcomes of biased receptor
      signaling may be further investigated or predicted. 

PMID- 25986937
TI  - Multi-class BCGA-ELM based classifier that identifies biomarkers associated with
      hallmarks of cancer.
AB  - BACKGROUND: Traditional cancer treatments have centered on cytotoxic drugs and
      general purpose chemotherapy that may not be tailored to treat specific cancers.
      Identification of molecular markers that are related to different types of
      cancers might lead to discovery of drugs that are patient and disease specific.
      This study aims to use microarray gene expression cancer data to identify
      biomarkers that are indicative of different types of cancers. Our aim is to
      provide a multi-class cancer classifier that can simultaneously differentiate
      between cancers and identify type-specific biomarkers, through the application of
      the Binary Coded Genetic Algorithm (BCGA) and a neural network based Extreme
      Learning Machine (ELM) algorithm. RESULTS: BCGA and ELM are combined and used to
      select a subset of genes that are present in the Global Cancer Mapping (GCM) data
      set. This set of candidate genes contains over 52 biomarkers that are related to
      multiple cancers, according to the literature. They include APOA1, VEGFC, YWHAZ,
      B2M, EIF2S1, CCR9 and many other genes that have been associated with the
      hallmarks of cancer. BCGA-ELM is tested on several cancer data sets and the
      results are compared to other classification methods. BCGA-ELM compares or
      exceeds other algorithms in terms of accuracy. We were also able to show that
      over 50% of genes selected by BCGA-ELM on GCM data are cancer related biomarkers.
      CONCLUSIONS: We were able to simultaneously differentiate between 14 different
      types of cancers, using only 92 genes, to achieve a multi-class classification
      accuracy of 95.4% which is between 21.6% and 38% higher than other results in the
      literature for multi-class cancer classification. Our findings suggest that
      computational algorithms such as BCGA-ELM can facilitate biomarker-driven
      integrated cancer research that can lead to a detailed understanding of the
      complexities of cancer.

PMID- 25986938
TI  - Identification and Quantification of Microplastics in Wastewater Using Focal
      Plane Array-Based Reflectance Micro-FT-IR Imaging.
AB  - Microplastics (<5 mm) have been documented in environmental samples on a global
      scale. While these pollutants may enter aquatic environments via wastewater
      treatment facilities, the abundance of microplastics in these matrices has not
      been investigated. Although efficient methods for the analysis of microplastics
      in sediment samples and marine organisms have been published, no methods have
      been developed for detecting these pollutants within organic-rich wastewater
      samples. In addition, there is no standardized method for analyzing microplastics
      isolated from environmental samples. In many cases, part of the identification
      protocol relies on visual selection before analysis, which is open to bias. In
      order to address this, a new method for the analysis of microplastics in
      wastewater was developed. A pretreatment step using 30% hydrogen peroxide (H2O2)
      was employed to remove biogenic material, and focal plane array (FPA)-based
      reflectance micro-Fourier-transform (FT-IR) imaging was shown to successfully
      image and identify different microplastic types (polyethylene, polypropylene,
      nylon-6, polyvinyl chloride, polystyrene). Microplastic-spiked wastewater samples
      were used to validate the methodology, resulting in a robust protocol which was
      nonselective and reproducible (the overall success identification rate was
      98.33%). The use of FPA-based micro-FT-IR spectroscopy also provides a
      considerable reduction in analysis time compared with previous methods, since
      samples that could take several days to be mapped using a single-element detector
      can now be imaged in less than 9 h (circular filter with a diameter of 47 mm).
      This method for identifying and quantifying microplastics in wastewater is likely
      to provide an essential tool for further research into the pathways by which
      microplastics enter the environment. 

PMID- 25986939
TI  - Vasculitis research: Don't slow down and plan for a life-time commitment.

PMID- 25986941
TI  - Ring-fused porphyrins: extension of pi-conjugation significantly affects the
      aromaticity and optical properties of the porphyrin pi-systems and the Lewis
      acidity of the central metal ions.
AB  - Here, we report the effects of ring fusion, which causes expansion of the pi
      conjugation circuits of the porphyrin derivatives to the fused meso-aryl groups,
      on the aromaticity and the magnetic properties of porphyrin derivatives. These
      studies revealed the facts that the ring fusion with five-membered rings causes
      not only the remarkable red shifts of the absorption bands and narrowed HOMO-LUMO
      gaps, but also the contribution of anti-aromatic resonance forms to the magnetic
      properties as observed in the (1)H NMR spectra. The optical absorption and
      magnetic circular dichroism (MCD) spectroscopies indicate that the increase in
      the number of the fused rings causes stabilization of the LUMO level of the
      porphyrin derivatives and as a result induces the loosening of the LUMO
      degeneracy that is generally observed for porphyrins. The electronic structure of
      a quadruply fused porphyrin derivative was experimentally clarified by the ESR
      studies on the 1e(-)-oxidized and 1e(-)-reduced species in THF. Furthermore, we
      revealed the substituent effects of the fused meso-aryl groups of quadruply fused
      porphyrins (QFPs) on the crystal structures, absorption spectra and redox
      potentials; the sensitiveness of the substituent effects shows that the pi
      conjugation circuits extended to the fused meso-aryl groups. Additionally, the
      elongation of the bond lengths between the pyrrolic nitrogen and the central
      metal ions in QFP-metal complexes causes a remarkable increase of the Lewis
      acidity of the central metal ions. 

PMID- 25986940
TI  - What matters for patients with vasculitis?
AB  - Advances in clinical care for patients with vasculitis have improved survival
      rates and created new challenges related to the ongoing management of chronic
      disease. Lack of curative therapies, burden of disease, treatment-related side
      effects, and fear of relapse contribute to patient-perceived reduction in quality
      of life. Patient-held beliefs about disease and priorities may differ
      substantially from the beliefs of their health care providers, and research
      paradigms are shifting to reflect more emphasis on understanding vasculitis from
      the patient's perspective. Efforts are ongoing to develop disease outcome
      measures in vasculitis that better represent the patient experience. Health care
      providers who care for patients with vasculitis should be sensitive to the
      substantial burdens of disease commonly experienced by patients living with the
      disease and should strive to provide comprehensive care directed towards the
      medical and biopsychological needs of these patients. 

PMID- 25986942
TI  - In oesophageal squamous cells, nitric oxide causes S-nitrosylation of Akt and
      blocks SOX2 (sex determining region Y-box 2) expression.
AB  - OBJECTIVE: Barrett's metaplasia might develop if GORD causes oesophageal squamous
      cells to convert into columnar cells. Acid and bile exposures upregulate columnar
      differentiation genes like CDX2 in oesophageal squamous cells, but it is not
      known if such exposures downregulate squamous differentiation genes like SOX2. In
      addition to acid and bile, patients with GORD also have high oesophageal
      concentrations of nitric oxide (NO). This study aims to determine how acid, bile
      salts and NO affect genes that influence oesophageal cell phenotype. DESIGN:
      Oesophageal squamous cells from patients with Barrett's oesophagus were exposed
      to acidic bile salts or NOC-9 (an NO donor). SOX2, p63 (squamous transcription
      factor) and CDX2 mRNAs were measured by quantitative RT-PCR. SOX2 and its
      regulatory Akt pathway proteins were evaluated by western blotting. S
      nitrosylation by NO was blocked by dithiothreitol. Immunohistochemistry for SOX2
      was performed on the oesophagus of rats with surgically induced GORD which were
      fed diets with and without nitrite supplementation. RESULTS: In oesophageal
      squamous cells, NO profoundly decreased SOX2 protein and caused a significantly
      greater decrease in SOX2 mRNA than did acidic bile salts. NO also decreased p63
      and increased CDX2 expression. NO caused S-nitrosylation of Akt, blocking its
      phosphorylation. Akt pathway inhibition by LY294002 or Akt siRNA reduced SOX2
      mRNA. Rats fed with nitrite-supplemented diets exhibited weaker SOX2 oesophageal
      staining than rats fed with normal diets. CONCLUSIONS: In oesophageal squamous
      cells, NO blocks SOX2 expression through Akt S-nitrosylation. NO also increases
      CDX2 and decreases p63 expression. By triggering molecular events preventing
      squamous differentiation while promoting intestinal differentiation, NO might
      contribute to Barrett's pathogenesis.

PMID- 25986943
TI  - A large randomised controlled intervention trial to prevent gastric cancer by
      eradication of Helicobacter pylori in Linqu County, China: baseline results and
      factors affecting the eradication.
AB  - OBJECTIVE: To clarify the full range of benefits and adverse consequences of
      Helicobacter pylori eradication as a strategy for gastric cancer prevention, the
      community-based intervention trial was launched in Linqu County, China. DESIGN: A
      total of 184,786 residents aged 25-54 years were enrolled in this trial and
      received (13)C-urea breath test. H. pylori positive participants were assigned
      into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or
      lookalike placebos together with a single dosage of omeprazole and bismuth.
      RESULTS: The prevalence of H. pylori in trial participants was 57.6%. A total of
      94,101 subjects completed the treatment. The overall H. pylori eradication rate
      was 72.9% in the active group. Gender, body mass index, history of stomach
      disease, baseline delta over baseline-value of (13)C-urea breath test, missed
      medication doses, smoking and drinking were independent predictors of eradication
      failure. The missed doses and high baseline delta over baseline-value were
      important contributors in men and women (all Ptrend<0.001). However, a dose
      response relationship between failure rate and smoking or drinking index was
      found in men (all Ptrend<0.001), while high body mass index (Ptrend<0.001) and
      history of stomach disease were significant predictors in women. The treatment
      failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and
      39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined.
      CONCLUSIONS: This large community-based intervention trial to eradicate H. pylori
      is feasible and acceptable. The findings of this trial lead to a distinct
      evaluation of factors influencing eradication that should be generally considered
      for future eradication therapies. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-10000979
      in accordance with WHO ICTRP requirements.

PMID- 25986944
TI  - A multicentre comparative prospective blinded analysis of EUS and MRI for
      screening of pancreatic cancer in high-risk individuals.
AB  - OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect
      precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk
      individuals (HRIs). It is unclear which screening technique is to be preferred.
      We aimed to compare the efficacy of EUS and MRI in their ability to detect
      clinically relevant lesions in HRI. DESIGN: Multicentre prospective study. The
      results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time
      screening by EUS and MRI are described. Clinically relevant lesions were defined
      as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts
      >=10 mm. Results were compared in a blinded, independent fashion. RESULTS: Two
      solid lesions (mean size 9 mm) and nine cysts >=10 mm (mean size 17 mm) were
      detected in nine HRI (6%). Both solid lesions were detected by EUS only and
      proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia
      2. Of the nine cysts >=10 mm, six were detected by both imaging techniques and
      three were detected by MRI only. The agreement between EUS and MRI for the
      detection of clinically relevant lesions was 55%. Of these clinically relevant
      lesions detected by both techniques, there was a good agreement for location and
      size. CONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions
      in 6% of HRI. Both imaging techniques were complementary rather than
      interchangeable: contrary to EUS, MRI was found to be very sensitive for the
      detection of cystic lesions of any size; MRI, however, might have some important
      limitations with regard to the timely detection of solid lesions.

PMID- 25986945
TI  - Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric
      bypass surgery and regulate hunger.
AB  - OBJECTIVE: Motilin-induced phase III contractions of the migrating motor complex
      (MMC) signal hunger in healthy volunteers. The current aim was to study the role
      of motilin as a hunger-inducing factor in obese patients and to evaluate the
      effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and
      hunger scores. DESIGN: Motilin and ghrelin plasma levels were determined during a
      complete MMC cycle in controls and obese patients selected for RYGB before, 6
      months and 1 year after surgery. 20 min after the end of the second phase III,
      obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was
      scored every 5 min. Hedonic hunger was assessed in obese patients with the Power
      of Food Scale questionnaire. RESULTS: Obesity caused a switch in the origin of
      phase III from antrum to duodenum. Obese patients had significantly higher
      motilin levels compared with controls during the MMC but tended to lack the
      motilin peak prior to phase III necessary to trigger hunger. Hunger scores during
      phase III were significantly lower in obese patients, but could be restored to
      control levels through the administration of a low dose of the motilin agonist,
      erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in
      parallel with hedonic hunger scores. CONCLUSIONS: Motilin may be an important
      regulator involved in the pathogenesis of obesity.

PMID- 25986946
TI  - Beyond endoscopic mucosal healing in UC: histological remission better predicts
      corticosteroid use and hospitalisation over 6 years of follow-up.
AB  - BACKGROUND: Endoscopic mucosal healing is an established treatment target for UC,
      yet the value of achieving histological remission remains unclear. AIMS: To
      evaluate histological remission compared to endoscopic mucosal healing for
      predicting patient outcomes in UC. METHODS: Blinded assessment of endoscopic and
      histological measures of disease activity was performed on patients with
      established UC at baseline. Concordance and prognostic values of endoscopic
      mucosal healing (defined by Baron score <=1) and histological remission (defined
      by Truelove and Richards' index) for predicting outcomes of corticosteroid use,
      hospitalisation and colectomy were determined over a median 6 years follow-up,
      including kappa statistics and Cox regression multivariate analysis. RESULTS: 91
      patients with UC were followed up for a median 72 months (IQR 54-75 months).
      Overall, concordance between endoscopic and histological remission was moderate
      (kappa=0.56, 95% CI 0.36 to 0.77); 24% patients had persistent inflammation
      despite endoscopic remission. Histological remission predicted corticosteroid use
      and acute severe colitis requiring hospitalisation over the follow-up period (HR
      0.42 (0.2 to 0.9), p=0.02; HR 0.21 (0.1 to 0.7), p=0.02; respectively), whereas
      endoscopic mucosal healing did not (HR 0.86, 95% CI 0.5 to 1.7, p0.65; HR 0.83
      95% CI 0.3 to 2.4, p0.74; respectively). CONCLUSIONS: Histological remission is a
      target distinct from endoscopic mucosal healing in UC and better predicts lower
      rates of corticosteroid use and acute severe colitis requiring hospitalisation,
      over a median of 6 years of follow-up. Our findings support the inclusion of
      histological indices in both UC clinical trials and practice, towards a target of
      'complete remission'.

PMID- 25986947
TI  - Adolescent body mass index and erythrocyte sedimentation rate in relation to
      colorectal cancer risk.
AB  - OBJECTIVE: Adult obesity and inflammation have been associated with risk of
      colorectal cancer (CRC); however, less is known about how adolescent body mass
      index (BMI) and inflammation, as measured by erythrocyte sedimentation rate
      (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort
      of 239 658 Swedish men who underwent compulsory military enlistment examinations
      in late adolescence (ages 16-20 years). DESIGN: At the time of the conscription
      assessment (1969-1976), height and weight were measured and ESR was assayed. By
      linkage to the national cancer registry, these conscripts were followed for CRC
      through 1 January 2010. Over an average of 35 years of follow-up, 885 cases of
      CRC occurred, including 501 colon cancers and 384 rectal cancers. Cox regression
      was used to estimate adjusted HRs and corresponding 95% CIs. RESULTS: Compared
      with normal weight (BMI 18.5 to <25 kg/m(2)) in late adolescence, upper
      overweight (BMI 27.5 to <30 kg/m(2)) was associated with a 2.08-fold higher risk
      of CRC (95% CI 1.40 to 3.07) and obesity (BMI 30+ kg/m(2)) was associated with a
      2.38-fold higher risk of CRC (95% CI 1.51 to 3.76) (p-trend: <0.001). Male
      adolescents with ESR (15+ mm/h) had a 63% higher risk of CRC (HR 1.63; 95% CI
      1.08 to 2.45) than those with low ESR (<10 mm/h) (p-trend: 0.006). Associations
      did not significantly differ by anatomic site. CONCLUSIONS: Late-adolescent BMI
      and inflammation, as measured by ESR, may be independently associated with future
      CRC risk. Further research is needed to better understand how early-life
      exposures relate to CRC.

PMID- 25986949
TI  - A supramolecular approach to improve the gene transfection efficacy of
      dendrimers.
AB  - Cyanuric acid is able to form complementary hydrogen bonds with melamine. Here,
      the specific recognition between cyanuric acid and melamine is used to
      significantly improve the gene transfection efficacy of low generation dendrimers
      via a supramolecular approach. 

PMID- 25986948
TI  - Regulation of autophagic cell death by glycogen synthase kinase-3beta in adult
      hippocampal neural stem cells following insulin withdrawal.
AB  - BACKGROUND: Neural stem cells (NSCs) hold great potential for the treatment of
      neurodegenerative diseases. However, programmed cell death (PCD) provoked by the
      harsh conditions evident in the diseased brain greatly undermines the potential
      of NSCs. Currently, the mechanisms of PCD that effect NSCs remain largely
      unknown. RESULTS: We have previously reported that hippocampal neural stem (HCN)
      cells derived from the adult rat brain undergo autopahgic cell death (ACD)
      following insulin withdrawal without hallmarks of apoptosis despite their normal
      apoptotic capabilities. In this study, we demonstrate that glycogen synthase
      kinase 3beta (GSK-3beta) induces ACD in insulin-deprived HCN cells. Both
      pharmacological and genetic inactivation of GSK-3beta significantly decreased
      ACD, while activation of GSK-3beta increased autophagic flux and caused more cell
      death without inducing apoptosis following insulin withdrawal. In contrast,
      knockdown of GSK-3alpha barely affected ACD, lending further support to the
      critical role of GSK-3beta. CONCLUSION: Collectively, these data demonstrate that
      GSK-3beta is a key regulator of ACD in HCN cells following insulin withdrawal.
      The absence of apoptotic indices in GSK-3beta-induced cell death in insulin
      deprived HCN cells corroborates the notion that HCN cell death following insulin
      withdrawal represents the genuine model of ACD in apoptosis-intact mammalian
      cells and identifies GSK-3beta as a key negative effector of NSC survival
      downstream of insulin signaling.

PMID- 25986950
TI  - Real-time monitoring of the metabolic activity of periodontopathic bacteria.
AB  - Bacterial metabolic activity is associated with the onset and progression
      mechanisms of oral biofilm-mediated disease; however, at present no method to
      monitor bacterial metabolism exists, especially for periodontopathic bacteria.
      Therefore, we aimed to establish a novel method for monitoring the metabolic
      activity of periodontopathic bacteria, Porphyromonas gingivalis (Pg), Prevotella
      intermedia (Pi) and Fusobacterium nucleatum (Fn), as well as Streptococcus mutans
      (Sm) for comparison. The method is based on the dye resazurin, which is converted
      to the fluorescent molecule resorufin by reducing molecules derived from
      bacterial metabolism. Additionally, the effects of antimicrobial substances on
      bacterial metabolic activity were evaluated using this method. When bacterial
      suspensions were incubated with tryptone, glutamate, aspartate or glucose in the
      presence of resazurin, the fluorescence intensity increased over time by these
      bacterial metabolic reactions, indicating that this method can be used to monitor
      the metabolic activity of periodontopathic bacteria. Chlorhexidine showed the 50%
      inhibitory concentration (IC50) of 15-49 MUg/ml for tryptone metabolism by Pg,
      Pi, and Fn, and 7.1-18 MUg/ml for glucose metabolism by Pi and Sm. The IC50s for
      cetylpyridinium chloride and sodium dodecyl sulfate were 0.8-2.1 and 28-44
      MUg/ml, respectively for all bacteria examined. Fluoride had no effect except the
      IC50 of 640 MUg/ml for Sm, while minocycline hydrochloride had no effect on any
      of the bacteria. The present study established the method for real-time
      monitoring of the metabolic activity of periodontopathic bacteria, and the method
      might be useful for evaluating the effects of antimicrobial substances on the
      bacterial metabolic activity.

PMID- 25986951
TI  - Histopathological classification of refractory chronic rhinosinusitis with nasal
      polyps.
AB  - OBJECTIVE: To delineate the histopathological characteristics of nasal mucosa in
      refractory chronic rhinosinusitis with nasal polyps (CRSwNP) in order to
      demonstrate subtypes of nasal polyps and their potential relation with lower
      airway comorbidity. STUDY DESIGN: Clinical- and pathological-based cross
      sectional study Methods: Nasal polyp specimens were prospectively collected from
      patients with refractory CRSwNP referred to our institution for endoscopic sinus
      surgery. Oral and topical steroids were stopped 1 month before surgery. The
      pathological analysis was conducted by 2 independent reviewers with light
      microscopy on Hematoxylin-Eosin-Saffron stained slides. Each observer fulfilled a
      standardized protocol with cell count and stromal characterization on the most
      representative field. Mean grading scores were established. Morphological aspects
      were compared with the cell distribution and the clinical conditions. RESULTS:
      Among 36 patients, three subtypes of nasal polyps were depicted: eosinophilic
      edematous (64%), fibrous (9%) and intermediate with mixed edematous and collagen
      stromal structure (27%). Basement membrane thickening and seromucous gland
      hyperplasia were observed in the fibrosis sub-type (p<0.03). Eosinophilic mucosal
      infiltrate was significantly increased (p=0.026) in patients with concomitant
      pulmonary disease (n=21). Nasal polyp distribution was not influenced by asthma,
      allergy, previous surgery and smoking. CONCLUSION: Our 3-subtype classification
      of refractory CRSwNP in Caucasian population shows a predominant edematous
      structure whatever the clinical conditions may have been. Eosinophilia as a major
      factor of adaptive immune response in nasal inflammation is a feature of
      concomitant pulmonary disease. Further studies concerning mucosal remodelling and
      outcome assessment after sinus surgery are required to evaluate the impact of our
      classification on a daily basis.

PMID- 25986952
TI  - Sociodemographic factors associated with infant abandonment in maternity
      hospitals in Kazakhstan: a case-control study.

PMID- 25986953
TI  - Structure, Mechanics, and Histology of Intraluminal Thrombi in Abdominal Aortic
      Aneurysms.
AB  - It has been recognized that the intraluminal thrombus (ILT) is a biologically
      active material contributing in the progression and rupture of abdominal aortic
      aneurysms (AAAs). To advance our understanding of the potential role of ILT in
      the natural history of AAAs, the structural, mechanical, and histological
      characteristics of ILTs have been studied with great interest over the past
      decade. Given that the ILT is evolving and changing its composition during AAA
      progression, attention has been paid to exploring the chemomechanical effects of
      ILT on the underlying wall properties. Various biomechanical and chemomechanical
      data, and related models have provided advanced insights into AAA pathogenesis
      which have served as a basis for clinical diagnosis. The goal of this review is
      to describe and summarize recent advances in the research of ILT found in the
      aorta in terms of structure, mechanics, and histology on a patient-specific
      basis. We point to some possible future studies which hopefully stimulate
      multidisciplinary research to address open problems. 

PMID- 25986954
TI  - Vascular Mechanics in Decellularized Aortas and Coronary Resistance Microvessels
      in Type 2 Diabetic db/db Mice.
AB  - We previously reported differences in stiffness between macro- and micro-vessels
      in type 2 diabetes (T2DM). The aim of this study was to define the mechanical
      properties of the ECM independent of vascular cells in coronary resistance micro
      vessels (CRMs) and macro-vessels (aorta) in control Db/db and T2DM db/db mice.
      Passive vascular remodeling and mechanics were measured in both intact and
      decellularized CRMs and aortas from 0 to 125 mmHg. We observed no differences in
      intact control and diabetic aortic diameters, wall thicknesses, or stiffnesses (p
      > 0.05). Aortic decellularization caused a significant increase in internal and
      external diameters and incremental modulus over a range of pressures that
      occurred to a similar degree in T2DM. Differences in aortic diameters due to
      decellularization occurred at lower pressures (0-75 mmHg) and converged with
      intact aortas at higher, physiological pressures (100-125 mmHg). In contrast, CRM
      decellularization caused increased internal diameter and incremental modulus only
      in the db/db mice, but unlike the aorta, the intact and decellularized CRM curves
      were more parallel. These data suggest that (1) micro-vessels may be more
      sensitive to early adverse consequences of diabetes than macro-vessels and (2)
      the ECM is a structural limit in aortas, but not CRMs. 

PMID- 25986956
TI  - The evolution of computational hemodynamics as a clinical tool in decision
      making, patient specific treatment and clinical management. Part II.

PMID- 25986955
TI  - Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized
      Bed Design.
AB  - The objective of this study was to develop a new high-efficiency dry powder
      inhaler (DPI) that can effectively aerosolize large masses (25-100 mg) of spray
      dried powder formulations. The DPI was designed to implement a concept similar to
      a fluidized bed for aerosolization using small mixing balls made of
      polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the
      powder. The performance of the fluidized bed DPI was compared, based on emitted
      dose (ED) and aerosolization efficiency, to other recently developed capsule
      based DPIs that were designed to accommodate smaller powder masses (~2-20 mg).
      The inhalers were tested with spray dried excipient enhanced growth (EEG)
      formulations that contained an antibiotic (ciprofloxacin) and hygroscopic
      excipient (mannitol). The new fluidized bed design produced an ED of 71% along
      with a mass median aerodynamic diameter of 1.53 MUm and fine particle fractions
      <5 and 1 MUm of 93 and 36%, respectively, when used to deliver a 100 mg loaded
      mass of EEG powder with the advantage of not requiring multiple capsules.
      Surprisingly, performance of the device was further improved by removing the
      mixing balls from the inhaler and only retaining the dose containment sphere.

PMID- 25986957
TI  - Imaging Findings and Management of Primary Breast Cancer in Accessory Axillary
      Breast Tissue.

PMID- 25986959
TI  - Frail phenotype and mortality prediction: a systematic review and meta-analysis
      of prospective cohort studies.
AB  - AIM: This study focused on older adults living in communities, primarily to
      investigate the relationship between physical frailty and mortality, and secondly
      to examine gender and age effects on the relationship between frailty and
      mortality. BACKGROUND: The World Health Organization indicated that frailty has
      become an indicator of a lack of successful aging. Systematic literature reviews
      have yet to focus on the association between various frailty phases and
      mortality. Meanwhile, few studies researched gender and age effects on the
      correlation between physical frailty and mortality among older adults living in
      communities. DESIGN: A systematic review and meta-analysis of prospective
      studies. METHOD: Frailty was assessed according to the Cardiovascular Health
      Study by Fried et al., who defined a frail phenotype as exhibiting the following
      five properties: weight loss, exhaustion, weakness, low physical activity, and
      mobility impairment. We included original epidemiologic population-based studies,
      cohort surveys, systematic reviews, and meta-analyses. Study samples included
      only adults aged 65 years or older who lived in communities. We excluded studies
      investigating hospitalised, institutionalised older adults, and those that
      examined disease-specific targets. We performed a pooled analysis of mortality of
      frailty by employing a random-effects model. RESULTS: A total of 35,538 older
      adults and 7994 deaths were included in the meta-analysis. We identified 11
      population-based studies that examined the relationship between mortality and
      frailty status in older adults. Compared with robust older adults, older people
      with frailty have the highest risks of mortality, followed by older people in the
      pre-frail phase. Older men with frailty have a higher risk of mortality than do
      frail older women. No age threshold for mortality risk was observed. CONCLUSION:
      Frailty is a prevalent and critical geriatric syndrome associated with decreased
      survival. Through geriatric assessment of frailty, essential information
      pertaining to mortality among older adults can be obtained.

PMID- 25986958
TI  - Comparison of Screened and Nonscreened Breast Cancer Patients in Relation to Age:
      A 2-Institution Study.
AB  - INTRODUCTION: Screening programs for breast cancer aim to allow early diagnosis,
      and thus reduce mortality. The aim of this study was to assess the effect of a
      population screening program in a sample of women aged between 50 and 69 years in
      terms of recurrence, metastasis, biological profiles, and survival, and to
      compare their results with those of women of a wider age range who did not
      participate on the screening program. PATIENTS AND METHODS: A prospective
      multicenter study in which 1821 patients with 1873 breast tumors who received
      surgery between 1999 and 2014 at MutuaTerrassa University Hospital and the
      Hospital of Terrassa in Barcelona were analyzed. A comparison was performed in
      the 50- to 69-year-old age group between those who participated on the screening
      program and those who did not. RESULTS: The mean age of patients was 58 years.
      The mean follow-up was 72 months, and median follow-up 59 months. The screened
      group showed significantly better results in all prognostic factors and in
      specific mortality than all nonscreened groups. The specific mortality rate in
      the screened patients was 2.4% (12/496), local recurrence 2.8% (14/496), and
      metastasis at 10 years 3.6% (18/496). In the nonscreened group, younger women
      presented a higher rate of metastasis (16.4% [81/493]) and a shorter disease-free
      period (77.1% [380/493]). The age group older than 70 years had the highest
      number of T4 tumors (7.5% [30/403]) and the highest proportion of radical surgery
      (50.4% [203/403]). CONCLUSION: Patients in the screening program presented
      improved survival. We speculate that extending breast cancer screening programs
      to women younger than 50 and older than 70 years could bring about mortality
      benefits.

PMID- 25986960
TI  - The patient experience of intensive care: a meta-synthesis of Nordic studies.
AB  - BACKGROUND: Sedation practices in the intensive care unit have evolved from deep
      sedation and paralysis toward lighter sedation and better pain management. The
      new paradigm of sedation has enabled early mobilization and optimized mechanical
      ventilator weaning. Intensive care units in the Nordic countries have been
      particularly close to goals of lighter or no sedation and a more humane approach
      to intensive care. OBJECTIVES: The aim of our study was to systematically review
      and reinterpret newer Nordic studies of the patient experience of intensive care
      to obtain a contemporary description of human suffering during life-threatening
      illness. DESIGN: We conducted a meta-synthesis in which we collected, assessed,
      and analyzed published qualitative studies with the goal of synthesizing these
      findings into a new whole. Analysis was based on the scientific approach of
      Gadamerian hermeneutics. SETTINGS: Nordic intensive care units. PARTICIPANTS:
      Patients in Nordic intensive care units. METHODS: We performed a literature
      search of qualitative studies of the patient experience of intensive care based
      on Nordic publications in 2000-2013. We searched the following databases: PubMed,
      CINAHL, Scopus, and PsycINFO. Each original paper was assessed by all authors
      using the Critical Appraisal Skills Program instrument for qualitative research.
      We included 22 studies, all of which provided direct patient quotes. RESULTS: The
      overarching theme was identified as: The patient experience when existence itself
      is at stake. We constructed an organizing framework for analysis using the main
      perspectives represented in the included studies: body, mind, relationships, and
      ICU-environment. Final analysis and interpretation resulted in the unfolding of
      four themes: existing in liminality, existing in unboundedness, existing in
      mystery, and existing on the threshold. CONCLUSIONS: Our main finding was that
      human suffering during intensive care is still evident although sedation is
      lighter and the environment is more humane. Our interpretation suggested that
      patients with life-threatening illness descend into a liminal state, where they
      face the choice of life or death. Caring nurses and family members play an
      important role in assisting the patient to transition back to life.

PMID- 25986962
TI  - Subjects At-Risk for Genetic Diseases in Portugal: Illness Representations.
AB  - This study investigates illness representations of subjects at-risk for 3
      autosomal dominant late-onset disorders: Familial Amyloid Polyneuropathy (FAP)
      TTR V30M, Huntington's disease (HD) and Machado-Joseph disease (MJD), comparing
      them with the illness representations of subjects at-risk for Hemochromatosis
      (HH). The present study included a clinical group that consisted of 213 subjects
      at genetic risk (FAP, HD and MJD), comprising 174 subjects at-risk for FAP, 34
      subjects at-risk for HD and only 5 subjects at-risk for MJD; and the control
      group consisting of 31 subjects at genetic risk for HH. All subjects at-risk were
      undergoing the process of genetic counseling to learn their genetic status
      (carrier or non-carrier). Subjects were assessed through a semi-structured single
      interview, in order to obtain sociodemographic data and the answer to an open
      ended question relating to the illness representation issue: "What does this
      illness mean to you?/ What is this disease to you?" It was in the subjects'
      metaphors that subjects best expressed what they felt regarding the disease and
      the situation of being at-risk for this disease. Family is their mirror and their
      source of learning and, therefore, it is inevitable that family is related to the
      meaning of the disease itself. 

PMID- 25986963
TI  - In vitro antiparasitic activity of microbial pigments and their combination with
      phytosynthesized metal nanoparticles.
AB  - Bioactive pigments were extracted and purified from cultures of Serratia
      marcescens and Chromobacterium violaceum. Spectroscopic, FTIR, and HPLC analyses
      showed prodigiosin and violacein as the principle molecules in the extract.
      Bioactive microbial pigments prodigiosin, violacein and their combinations with
      phytosynthesized silver and gold nanoparticles were studied for in vitro growth
      inhibition of Plasmodium falciparum and Trypanosoma brucei gambiense. Prodigiosin
      was found to be more effective than violacein for inhibition of both parasites in
      vitro. Specifically, combinations of the microbial pigment prodigiosin with metal
      nanoparticles showed a significant decrease in the IC50 values on both parasites
      (2.7 to 3.6 fold) without increase of cytotoxicity upon mammalian cells. The data
      may be useful for the microbial pigment based drug designing. 

PMID- 25986965
TI  - The bicuspid aortic valve aortopathy mystery continues: Are we that mediocre?

PMID- 25986966
TI  - Perceived foreign accentedness: acoustic distances and lexical properties.
AB  - In this study, we examined speaker-dependent (acoustic) and speaker-independent
      (lexical) linguistic influences on perceived foreign accentedness. Accentedness
      ratings assigned to Chinese-accented English words were analyzed, taking
      accentedness as a continuum. The speaker-dependent variables were included as
      acoustic distances, measured in relation to typical native-speaker values. The
      speaker-independent variable measures were related to the properties of
      individual words, not influenced by the speech signal. To the best of the
      authors' knowledge, this represents the first attempt to examine speaker
      dependent and speaker-independent variables simultaneously. The model indicated
      that the perception of accentedness is affected by both acoustic goodness of fit
      and lexical properties. The results are discussed in terms of matching
      variability in the input to multidimensional representations. 

PMID- 25986967
TI  - RACK1, scaffolding a heterotrimeric G protein and a MAPK cascade.
AB  - Scaffold proteins of mitogen-activated protein kinase (MAPK) cascades play
      crucial roles in determining signal specificity, amplitude, and duration in yeast
      and mammals. Recently, RACK1 was identified as the first plant MAPK scaffold
      protein that connects heterotrimeric G protein with a MAPK cascade to form a
      unique signaling pathway in plant immunity.

PMID- 25986964
TI  - Brain and cognition abnormalities in long-term anabolic-androgenic steroid users.
AB  - BACKGROUND: Anabolic-androgenic steroid (AAS) use is associated with psychiatric
      symptoms including increased aggression as well as with cognitive dysfunction.
      The brain effects of long-term AAS use have not been assessed in humans. METHODS:
      This multimodal magnetic resonance imaging study of the brain compared 10 male
      weightlifters reporting long-term AAS use with 10 age-matched weightlifters
      reporting no AAS exposure. Participants were administered visuospatial memory
      tests and underwent neuroimaging. Brain volumetric analyses were performed;
      resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of
      interest analysis focused on the amygdala; and dorsal anterior cingulate cortex
      (dACC) metabolites were quantified by proton magnetic resonance spectroscopy
      (MRS). RESULTS: AAS users had larger right amygdala volumes than nonusers
      (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic,
      hippocampal, and visual cortical areas. Left amygdala volumes were slightly
      larger in AAS users (P=0.061) but few group differences were detected in left
      amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and
      higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased
      glutamate turnover. On a visuospatial cognitive task, AAS users performed more
      poorly than nonusers, with the difference approaching significance (P=0.053).
      CONCLUSIONS: Long-term AAS use is associated with right amygdala enlargement and
      reduced right amygdala rsFC with brain areas involved in cognitive control and
      spatial memory, which could contribute to the psychiatric effects and cognitive
      dysfunction associated with AAS use. The MRS abnormalities we detected could
      reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or
      neurodegenerative processes, which could contribute to AAS-associated cognitive
      dysfunction.

PMID- 25986968
TI  - Why are there so few species of ferns?
AB  - A recent study has documented a natural hybridization event between two fern
      lineages that last shared a common ancestor about 60 million years ago. This is
      one of the deepest hybridization events ever described and has important
      implications for plant speciation theory.

PMID- 25986969
TI  - The inhibitory effect of Isoflavones isolated from Caesalpinia pulcherrima on
      aldose reductase in STZ induced diabetic rats.
AB  - Increased aldose reductase activity has been implicated in the development of
      retinopathy due to accumulation of intracellular sugar alcohol, i.e., sorbitol.
      In this study, the compounds isolated from the Caesalpinia pulcherrima, have been
      examined for its inhibitory effects on aldose reductase (AR), which plays a major
      role in diabetic retinopathy. 3,6,7,4',5'-Pentamethoxy-5,3'-dihydroxyflavone
      (Compound 2) has shown significant inhibition of rat retina AR with an IC50 value
      of 16.24+/-0.046MUM in a non-competitive manner. Molecular docking study results
      are steady with the pattern of AR inhibition by Compound 2 and its specificity.
      The supplementation of Compound 2 suppresses sorbitol accumulation in retina by
      decreased AR activity in STZ induced diabetic rat in dose dependent manner.
      Besides this, rats fed with Compound 2 have shown improved levels of antioxidant
      enzymes. This study revealed that Compound 2 has pharmacologically active
      component with a potential to inhibit rat retina AR and affecting the delaying
      process of diabetic retinopathy in STZ induced diabetic rats. 

PMID- 25986970
TI  - Induction and repair of DNA cross-links induced by sulfur mustard in the A-549
      cell line followed by a comet assay.
AB  - Sulfur mustard is a highly toxic chemical warfare agent with devastating impact
      on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions
      induced in the cell by sulfur mustard. The comet assay is a very sensitive method
      for measuring DNA damage. In the present study using the A-549 lung cell line,
      the comet assay protocol was optimized for indirect detection of DNA cross-links
      induced by sulfur mustard. The method is based on the additional treatment of the
      assayed cells containing cross-links with the chemical mutagen, styrene oxide.
      Alkali-labile adducts of styrene oxide cause DNA breaks leading to the formation
      of comets. A significant dose-dependent reduction of DNA migration of the comet's
      tail was found after exposing cells to sulfur mustard, indicative of the amount
      of sulfur mustard induced cross-links. The remarkable decrease of % tail DNA
      could be observed as early as 5min following exposure to sulfur mustard and the
      maximal effect was found after 30min, when DNA migration was reduced to the
      minimum. Sulfur mustard preincubated in culture medium without cells lost its
      ability to induce cross-links and had a half-life of about 15min. Pre-incubation
      longer than 30min does not lead to a significant increase in cross-links when
      applied to cells. However, the amount of cross-links is decreased during further
      incubation due to repair. The current modification of the comet assay provides a
      useful tool for detecting DNA cross-links induced by sulfur mustard and could be
      used for detection of other DNA cross-linking agents such as chemotherapeutic
      drugs. 

PMID- 25986971
TI  - Tolerance of entomopathogenic fungi to ultraviolet radiation: a review on
      screening of strains and their formulation.
AB  - Ultraviolet radiation from sunlight is probably the most detrimental
      environmental factor affecting the viability of entomopathogenic fungi applied to
      solar-exposed sites (e.g., leaves) for pest control. Most entomopathogenic fungi
      are sensitive to UV radiation, but there is great inter- and intraspecies
      variability in susceptibility to UV. This variability may reflect natural
      adaptations of isolates to their different environmental conditions. Selecting
      strains with outstanding natural tolerance to UV is considered as an important
      step to identify promising biological control agents. However, reports on
      tolerance among the isolates used to date must be analyzed carefully due to
      considerable variations in the methods used to garner the data. The current
      review presents tables listing many studies in which different methods were
      applied to check natural and enhanced tolerance to UV stress of numerous
      entomopathogenic fungi, including several well-known isolates of these fungi. The
      assessment of UV tolerance is usually conducted with conidia using dose-response
      methods, wherein the UV dose is calculated simply by multiplying the total
      irradiance by the period (time) of exposure. Although irradiation from lamps
      seldom presents an environmentally realistic spectral distribution, laboratory
      tests circumvent the uncontrollable circumstances associated with field assays.
      Most attempts to increase field persistence of microbial agents have included
      formulating conidia with UV protectants; however, in many cases, field efficacy
      of formulated fungi is still not fully adequate for dependable pest control. 

PMID- 25986972
TI  - Optimization of in vitro regeneration and Agrobacterium tumefaciens-mediated
      transformation with heat-resistant cDNA in Brassica oleracea subsp. italica cv.
      Green Marvel.
AB  - An efficient system for shoot regeneration and Agrobacterium tumefaciens-mediated
      transformation of Brassica oleracea cv. Green Marvel cultivar is described. This
      study focuses on developing shoot regeneration from hypocotyl explants of
      broccoli cv. Green Marvel using thidiazuron (TDZ), zeatin, and kinetin, the
      optimization of factors affecting Agrobacterium-mediated transformation of the
      hypocotyl explants with heat-resistant cDNA, followed by the confirmation of
      transgenicity of the regenerants. High shoot regeneration was observed in 0.05
      0.1 mg dm(-3) TDZ. TDZ at 0.1 mg dm(-3) produced among the highest percentage of
      shoot regeneration (96.67 %) and mean number of shoot formation (6.17). The
      highest percentage (13.33 %) and mean number (0.17) of putative transformant
      production were on hypocotyl explants subjected to preculture on shoot
      regeneration medium (SRM) with 200 uM acetosyringone. On optimization of
      bacterial density and inoculation time, the highest percentage and mean number of
      putative transformant production were on hypocotyl explants inoculated with a
      bacterial dilution of 1:5 for 30 min. Polymerase chain reaction (PCR) assay
      indicated a transformation efficiency of 8.33 %. The luciferase assay showed
      stable integration of the Arabidopsis thaliana HSP101 (AtHSP101) cDNA in the
      transgenic broccoli regenerants. Three out of five transgenic lines confirmed
      through PCR showed positive hybridization bands of the AtHSP101 cDNA through
      Southern blot analysis. The presence of AtHSP101 transcripts in the three
      transgenic broccoli lines indicated by reverse transcription-PCR (RT-PCR)
      confirmed the expression of the gene. In conclusion, an improved regeneration
      system has been established from hypocotyl explants of broccoli followed by
      successful transformation with AtHSP101 for resistance to high temperature. 

PMID- 25986973
TI  - Mutual information against correlations in binary communication channels.
AB  - BACKGROUND: Explaining how the brain processing is so fast remains an open
      problem (van Hemmen JL, Sejnowski T., 2004). Thus, the analysis of neural
      transmission (Shannon CE, Weaver W., 1963) processes basically focuses on
      searching for effective encoding and decoding schemes. According to the Shannon
      fundamental theorem, mutual information plays a crucial role in characterizing
      the efficiency of communication channels. It is well known that this efficiency
      is determined by the channel capacity that is already the maximal mutual
      information between input and output signals. On the other hand, intuitively
      speaking, when input and output signals are more correlated, the transmission
      should be more efficient. A natural question arises about the relation between
      mutual information and correlation. We analyze the relation between these
      quantities using the binary representation of signals, which is the most common
      approach taken in studying neuronal processes of the brain. RESULTS: We present
      binary communication channels for which mutual information and correlation
      coefficients behave differently both quantitatively and qualitatively. Despite
      this difference in behavior, we show that the noncorrelation of binary signals
      implies their independence, in contrast to the case for general types of signals.
      CONCLUSIONS: Our research shows that the mutual information cannot be replaced by
      sheer correlations. Our results indicate that neuronal encoding has more
      complicated nature which cannot be captured by straightforward correlations
      between input and output signals once the mutual information takes into account
      the structure and patterns of the signals.

PMID- 25986974
TI  - [Pro-inflammatory serum cytokines in diabetic retinopathy].
AB  - BACKGROUND: Pro-inflammatory cytokines play an important role in diabetic
      retinopathy. There is conflicting evidence about their serum elevation in this
      condition and that they also may be possible serum inflammatory biomarkers of
      diabetic retinopathy. OBJECTIVE: To evaluate the presence of serum pro
      inflammatory cytokines and acute phase reactants in the serum of patients with
      and without diabetic retinopathy. MATERIAL AND METHODS: Comparative case series
      with 36 patients divided into three groups were included: 12 patients with
      diabetes mellitus and diabetic retinopathy (group 1), 12 diabetic patients
      without diabetic retinopathy (group 2), and 12 healthy patients as a control
      group. Serum levels of the following pro-inflammatory cytokines were measured in
      all patients: TNF-alpha, IL-1beta and IL-6. Pro-inflammatory biomarkers
      measurements were also performed, such as erythrocyte sedimentation rate and C
      reactive protein. RESULTS: The levels of TNF-alpha and IL-6 were higher in group
      1 (TNF-alpha: 19.4 +/- 10.9 pg/ml, IL-6: 5.75 +/- 7 pg/ml) compared to the other
      two groups, although the difference was statistically significant only in the
      case of TNF-alpha (group 1: 19.4 +/- 10.9 pg/ml, group 2: 14 +/- 4.3 pg/ml and
      control: 8.49 +/- 3.69 pg/ml, p = 0.001). There were no differences among pro
      inflammatory biomarkers such as erythrocyte sedimentation rate and C reactive
      protein. among the three groups (p > 0.05). CONCLUSIONS: Pro-- inflammatory serum
      cytokine levels were higher in the diabetes mellitus with diabetic retinopathy
      group. Larger studies are warranted to establish the real impact of this finding.

PMID- 25986975
TI  - [Inflammatory pseudotumour of the liver. Importance of intra-operative
      histopathology].
AB  - BACKGROUND: Inflammatory pseudotumour is a rare entity, considered benign, and
      characterised by inflammatory cell mesenchymal proliferation. CLINICAL CASE: The
      case is presented 70 year-old man with fever of unknown origin syndrome. He was
      diagnosed with liver abscesses (one segment IV, adjacent to gallbladder fundus
      and segment VI), who progressed slowly after antibiotic treatment. In the absence
      of a diagnosis, although fine needle puncture-aspiration and different imaging
      tests were performed, elective surgery was decided. The intra-operative
      histopathology reported the existence of an inflammatory pseudotumour.
      CONCLUSIONS: Inflammatory pseudotumours are clinically classified into different
      types according to their aetiology, varying therapeutic management based on the
      same. It is very difficult to diagnose because of the absence of symptoms, blood
      disorders, or specific radiological findings. Definitive diagnosis often requires
      histopathological confirmation, in most cases by percutaneous liver puncture, but
      sometimes exploratory laparotomy or even performing a hepatectomy for
      confirmation is necessary. The natural history of inflammatory pseudotumour is
      its regression; thus conservative management may be used through regular checks
      until resolution, or can be treated with antibiotics, anti-inflammatories and
      even corticosteroids. Surgical resection is indicated for persistent unresolved
      systemic symptoms despite medical treatment, in those situations where growth is
      evident, with or without symptoms, when involving the hepatic hilum, and finally,
      in case where the possibility of malignancy cannot be ruled out.

PMID- 25986976
TI  - [Cell signaling pathways interaction in cellular proliferation: Potential target
      for therapeutic interventionism].
AB  - Nowadays, cellular physiology is best understood by analysing their interacting
      molecular components. Proteins are the major components of the cells. Different
      proteins are organised in the form of functional clusters, pathways or networks.
      These molecules are ordered in clusters of receptor molecules of extracellular
      signals, transducers, sensors and biological response effectors. The
      identification of these intracellular signaling pathways in different cellular
      types has required a long journey of experimental work. More than 300
      intracellular signaling pathways have been identified in human cells. They
      participate in cell homeostasis processes for structural and functional
      maintenance. Some of them participate simultaneously or in a nearly-consecutive
      progression to generate a cellular phenotypic change. In this review, an analysis
      is performed on the main intracellular signaling pathways that take part in the
      cellular proliferation process, and the potential use of some components of these
      pathways as target for therapeutic interventionism are also underlined. 

PMID- 25986977
TI  - [Profile of the patient with failed back surgery syndrome in the National
      Institute of Rehabilitation. Comparative analysis].
AB  - BACKGROUND: Failed back surgery syndrome is a complication of spine surgery that
      leads to chronic pain and disability, often with disastrous emotional
      consequences to the patient. AIM: To compare the profile of patients whose first
      surgery was performed in our hospital versus a group that underwent first spine
      surgery in a different centre. METHODS: Retrospective study with 65 patients; 18
      formed group I (first spine surgery performed in our institution), and 47
      patients in group II (first surgery performed in another hospital). Background,
      demographic, clinical features and functional status were compared. In group I
      the majority of the cases had a previous diagnosis of lumbar stenosis (group I
      44.4% vs group II 25.5% p = 0.22), whereas disk herniation was the main diagnosis
      in group II (group I 22.2% vs group II 61.7% p = 0.001). The main cause of the
      syndrome in group I was technical error during surgery (61.1%), while in group II
      this cause represented only 6.3% (p=.001). Among the patients of this latter
      group, misdiagnosis was highly prevalent (57.4%), against no cases in group I
      (p=.001). The preoperative functional status between both groups and their
      recovery in the immediate postoperative period was similar (p = 0.68).
      CONCLUSIONS: This study suggests that the diagnostic and treatment standards are
      different between healthcare centres, specifically between academic centres vs.
      private practice.

PMID- 25986978
TI  - [Splenic artery aneurysm. Report of a case].
AB  - BACKGROUND: The incidence of splenic artery aneurysm is not well known because
      they are often asymptomatic. CLINICAL CASE: The case is presented of a 40 year
      old woman diagnosed with a splenic artery aneurysm. She was clinically
      asymptomatic. A three-dimensional angiographic study was performed. The artery
      embolisation was rejected, according to the results of the study; thus it was
      decided to perform a laparoscopic splenic-aneurysmectomy. CONCLUSIONS: Splenic
      artery aneurysms may present with non-specific symptoms, such as abdominal pain
      or anorexia. However 2-10% of aneurysms debut as spontaneous rupture. For this
      reason treatment is indicated in symptomatic aneurysms or those with rupture risk
      factors. In these cases there are different possibilities, such as therapeutic
      embolisation, endovascular stenting or surgery. Surgical approach varies
      depending on the location of the aneurysm in the splenic artery, enabling
      aneurysmectomy, splenic-aneurysmectomy, or aneurysm exclusion to be performed.

PMID- 25986979
TI  - [Abdominal wall actinomycosis. A report of a case].
AB  - BACKGROUND: Abdominal wall Actinomycosis is a rare disease associated with the
      use of intrauterine device and as a complication of abdominal surgery. Diagnosis
      is difficult because it is unusual and behaves like a malignant neoplasm. AIM: A
      case report is presented of a patient who had used an intrauterine device for
      four years and developed a stony tumour in the abdominal wall associated with a
      set of symptoms that, clinically and radiologically, was simulating a peritoneal
      carcinomatosis associated with paraneoplastic syndrome, even in the course of an
      exploratory laparotomy. CLINICAL CASE: The patient attended our hospital with a
      two-month history of abdominal pain and symptoms that mimic a paraneoplastic
      syndrome. The diagnosis of abdominal actinomycosis was suspected by the finding
      of the microorganism in cervical cytology together with other cultures and
      Actinomyces negative in pathological studies, confirming the suspicion of a
      complete cure with empirical treatment with penicillin. CONCLUSIONS:
      Actinomycosis should be considered in patients with pelvic mass or abdominal wall
      mass that mimics a malignancy. Antibiotic therapy is the first treatment choice
      and makes a more invasive surgical management unnecessary.

PMID- 25986980
TI  - [Bronchogenic cysts. Importance of infection in adults. Study of 12 cases].
AB  - BACKGROUND: Bronchogenic cyst is a rare congenital malformation and commonly
      located in the mediastinum and lung parenchyma. OBJECTIVE: To determine the
      clinical characteristics of the patients with diagnosis of bronchogenic cysts,
      their location and the infectious bacteria when the cysts are infected. The cases
      were collected from 1 January 2005 to 1 January 2013, in a third level hospital.
      MATERIAL AND METHODS: The cases with bronchogenic cysts resected by thoracotomy
      were confirmed by histological study. Age, sex, admission diagnosis, location,
      size, imagenologic studies, and bacteriological cultures were evaluated. RESULTS:
      Of the 12 cases with diagnosis of bronchogenic cysts surgically resected by
      thoracotomy, six were male and six female, with 50% located in lung parenchyma
      and 50% in mediastinum, one of the latter was para-oesophageal. Bacteriological
      study of the cystic content demonstrated bacterial infection in seven (58%)
      cases. CONCLUSIONS: Bronchogenic cysts are rare congenital benign lesions. They
      must be resected because their content might be infected. The histopathology
      study is necessary to confirm the diagnosis, together with bacteriological
      examination. Thoracotomy is a safe procedure to resect bronchogenic cysts.

PMID- 25986981
TI  - [Traumatic occipitocervical and atlantoaxial dislocation with clivus fracture in
      a child. Case report].
AB  - BACKGROUND: Cranieovertebral junction lesions in the paediatric population are
      associated with a low survival rate, which has declined in recent years.
      Neurological disability is a major concern due to the high economical cost it
      represents. Paediatric patients are more susceptible to this lesion because of
      hyperextension capacity, flat articulation, and increased ligamentous laxity.
      Survival after these kinds of injuries has been more often reported in adults,
      but are limited in the paediatric population. CLINICAL CASE: A case is reported
      of an 8-year-old male with occipitocervical and atlantoaxial dislocation
      associated with clivus fracture, brain oedema, and post-traumatic subarachnoid
      haemorrhage (SAH). A halo vest system was placed with no traction. One month
      after the trauma the patient was surgically treated with C1 and C2 trans
      articular screws, occipitocervical fixation with plate and screws, and C1- C2
      fixation with tricortical bone graft and wires without complication. He has now
      returned to school and is self-sufficient. CONCLUSIONS: With better pre-hospital
      medical care and with improved surgical techniques the mortality rate has
      declined in this kind of lesion.

PMID- 25986982
TI  - [Enterolithotomy and early cholecystectomy, an application of damage control
      surgery for patients with gallstone ileus].
AB  - BACKGROUND: Recurrent gallstone ileus is an uncommon mechanical intestinal
      obstruction secondary to occlusion of the intestine by an intraluminal biliary
      calculus. CLINICAL CASE: Female, 75 years old, ischaemic heart disease (stent),
      arrived in our department complaining of abdominal pain and vomiting. Computed
      tomography showed gallstone ileus. The patient underwent an enterotomy with
      gallstone removal. Three months later, the patient came back with the same
      clinical symptoms and signs. A new computed tomography highlighted a gallstone
      ileus again. Enterolithotomy and gallstone removal, cholecystectomy and closure
      of cholecystoduodenal fistula were performed. The patient had a prolonged
      hospital stay due to the development of congestive heart failure. Case 2. Male,
      71 years old, ischaemic heart disease and aortocoronary bypass, seen in our
      department complaining of vomiting. Computed tomography showed aerobilia and
      gallstone ileus. The patient underwent an urgent enterolithotomy. Seven months
      later, the patient came back with the same clinical symptoms and signs. Computed
      tomography showed a new gallstone ileus. An enterotomy and gallstone removal,
      cholecystectomy and closure of cholecystoduodenal fistula were performed. The
      patient died due to multi-organ failure in post-surgery period. CONCLUSION: In
      the elderly patients with concomitant medical illnesses with the risk of a second
      laparotomy, it is justifiable to reconsider the definitive repair in the
      treatment of gallstone ileus. The enterolithotomy in acute phase followed by
      early cholecystectomy (4-8 weeks) may be a safe method for eliminating, not only
      the possibility of recurrent gallstone ileus, and probably the need for a second
      laparotomy, but also the exceptional possibility of developing a gallbladder
      carcinoma.

PMID- 25986983
TI  - [Primary malignant melanoma of the central nervous system: A diagnostic
      challenge].
AB  - BACKGROUND: The rare incidence of primary malignant melanoma of the central
      nervous system and its ability to mimic other melanocytic tumors on images makes
      it a diagnostic challenge for the neurosurgeon. CLINICAL CASE: A 51-year-old
      patient, with a tumor located in the right forniceal callosum area. Total
      surgical excision was performed. Histopathological result was consistent with the
      diagnosis of primary malignant melanoma of the central nervous system, after
      ruling out extra cranial and extra spinal melanocytic lesions. CONCLUSIONS: The
      primary malignant melanoma of the central nervous system is extremely rare. There
      are features in magnetic resonance imaging that increase the diagnostic
      suspicion; nevertheless there are other tumors with more prevalence that share
      some of these features through image. Since there is not an established
      therapeutic standard its prognosis is discouraging.

PMID- 25986984
TI  - [Craniocerebral gunshot wounds in civilian population: Analysis of experience in
      a single center in Monterrey, Mexico].
AB  - BACKGROUND: Gunshot wounds in civilian population of Mexico were quite rare.
      Currently, conflicts amongst organized crime groups are carried out with weapons,
      which are considered as exclusive use by the nations army. OBJECTIVES: Describe
      the experience of our institution and share results of clinical and radiological
      factors influencing the prognosis of the patients. MATERIAL AND METHODS:
      Observational and retrospective study of patients with cranial gunshot wounds
      (GSW), which penetrated the duramater, treated from January 2009 - January 2013.
      We considered several demographic variables, Glasgow Coma Scale (GCS), upon
      admission, state of pupils, type of surgery and size of decompression, Glasgow
      Outcome Score (GOS) upon discharge, and after 6 months. RESULTS: Of 68 patients,
      we excluded those whose duramater was not penetrated, leaving 52 patients. The
      average age was 28.7 years, and 80.8% were males. All were surgically intervened,
      with 8% of general mortality. Mortality in the GCS 3 to 5 points group was 43%,
      from the 6 to 8 points it was 6%, and no deaths in the 9 to 15 points. In
      patients with both pupils fixed, anisocoric and isocoric, mortality was 67%, 7%,
      and 3%, respectively. Bihemispheric, multilobar and unihemispheric trajectory of
      the bullet plus ventricular compromise was related to a Glasgow Outcome Score <=
      3 upon discharge in 90.9% of the cases. CONCLUSIONS: GCS upon admission and state
      of the pupils are the most influential factors in the prognosis. Patients with a
      GCS > 8 < 13 points upon admission, normal pupillary response, without
      ventricular compromise can benefit with early and aggressive surgical treatment.

PMID- 25986986
TI  - Editorial Comment.

PMID- 25986987
TI  - Editorial Comment.

PMID- 25986988
TI  - Editorial Comment.

PMID- 25986989
TI  - Single-cell analysis of mast cell degranulation induced by airway smooth muscle
      secreted chemokines.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease characterized by narrowed
      airways, bronchial hyper-responsiveness, mucus hyper-secretion, and airway
      remodeling. Mast cell (MC) infiltration into airway smooth muscle (ASM) is a
      defining feature of asthma, and ASM regulates the inflammatory response by
      secreting chemokines, including CXCL10 and CCL5. Single cell analysis offers a
      unique approach to study specific cellular signaling interactions within large
      and complex signaling networks such as the inflammatory microenvironment in
      asthma. METHODS: Carbon-fiber microelectrode amperometry was used to study the
      effects of ASM-secreted chemokines on mouse peritoneal MC degranulation. RESULTS:
      MC degranulation in response to CXCL10 and CCL5 was monitored at the single cell
      level. Relative to IgE-mediated degranulation, CXCL10- and CCL5-stimulated MCs
      released a decreased amount of serotonin per granule with fewer release events
      per cell. Decreased serotonin release per granule was correlated with increased
      spike half-width and rise-time values. CONCLUSIONS: MCs are directly activated by
      ASM-associated chemokines. CXCL10 and CCL5 induce less robust MC degranulation
      compared to IgE- and A23187-stimulation. The kinetics of MC degranulation are
      signaling pathway-dependent, suggesting a biophysical mechanism of regulated
      degranulation that incorporates control over granule trafficking, transport, and
      docking machinery. GENERAL SIGNIFICANCE: The biophysical mechanisms, including
      variations in number of exocytotic release events, serotonin released per
      granule, and the membrane kinetics of exocytosis that underlie MC degranulation
      in response to CXCL10 and CCL5 were characterized at the single cell level. These
      findings clarify the function of ASM-derived chemokines as instigators of MC
      degranulation relative to classical mechanisms of MC stimulation.

PMID- 25986990
TI  - Chinese herbal medicinal ingredients affect secretion of NO, IL-10, ICAM-1 and IL
      2 by endothelial cells.
AB  - The aim of this study was to investigate the anti-endotoxin effects of
      sinomenine, fangchinoline, stachydrine, chuanxionggzine, oxymartrine and
      evodiamine alkaloids commonly found in Chinese herbal medicines. Porcine
      endothelial cells were challenged with 1 MUg LPS/ml for 3 h and then treated with
      one of the six alkaloids at three concentrations (1, 5 or 10 MUg/ml) for a
      further 21 h. The supernatants of the cultures were then collected and analyzed
      for levels of nitric oxide (NO), interleukin (IL)-10, intercellular cell adhesion
      molecule-1 (ICAM-1) and IL-2 using ELISA kits. The results revealed that
      sinomenine, stachydrine and chuanxionggzine inhibited production of NO;
      stachydrine and evodiamine inhibited secretion of IL-10; sinomenine and
      chuanxionggzine down-regulated ICAM-1 expression; oxymartrine and evodiamine
      decreased production of IL-2 by the LPS-stimulated endothelial cells. Overall,
      the data from these studies suggested to us that these six alkaloids might
      effectively reduce inflammatory responses in situ via changes in the formation of
      these key regulatory molecules/proteins.

PMID- 25986991
TI  - Paeoniflorin regulates the function of human peripheral blood mononuclear cells
      stimulated by rhIL-1beta by up-regulating Treg expression.
AB  - The aim of the present study was to investigate the effect of paeoniflorin (Pae)
      on recombinant human interleukin-1beta (rhIL-1beta)-stimulated human peripheral
      blood mononuclear cells (PBMCs) in vitro. PBMCs were collected by Ficoll density
      gradient centrifugation and were co-cultured with rhIL-1beta for different time
      periods. The proliferation response was determined by a cell counting kit-8 (CCK
      8) assay. The production of IL-17 and IL-10 was measured by enzyme-linked
      immunosorbent assay (ELISA). The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T
      cells (Treg) was detected by flow cytometry analysis. These results indicated
      that rhIL-1beta stimulation induced the proliferation of PBMCs in a concentration
      and time-dependent manner; it also increased the level of IL-17 and decreased
      the level of IL-10 in a concentration-dependent manner. The flow cytometry
      analysis demonstrated that the stimulation of rhIL-1beta significantly
      downregulated the percentage of CD4(+)CD25(+)Foxp3(+) Treg in CD4(+) T cells.
      However, administration of Pae significantly suppressed the proliferation
      response of rhIL-1beta-induced PBMCs and regulated the secretion function of IL
      17 and IL-10. Additional experiments demonstrated that Pae treatment
      significantly reduced rhIL-1beta-induced decreases in PBMCs CD4(+)CD25(+)Foxp3(+)
      subpopulation numbers. These results suggest that the anti-inflammatory action of
      Pae is attributable to its regulation of IL-17/IL-10 secretion and Treg
      expression. 

PMID- 25986992
TI  - Sickle cell disease is associated with iron mediated hypercoagulability.
AB  - Sickle cell disease (SCD) is associated with a significant hypercoagulable state
      and several hemostatic anomalies have been identified in this disease state. Of
      interest, SCD patients can become iron overloaded after transfusion, and iron can
      enhance fibrinogen as a substrate for thrombin, resulting in thrombi that
      commence coagulation quickly and form rapidly. We hypothesized that SCD patients
      would display hypercoagulable plasma coagulation kinetics and an iron enhancement
      of coagulation. After obtaining IRB approval, we assessed coagulation kinetics
      and iron enhancement with viscoelastic methods in archived, citrated plasma
      obtained from ambulatory or hospitalized SCD patients (n = 20). All SCD patients
      had plasmatic hypercoagulability, and 65 % were positive for iron enhancement of
      coagulation. In conclusion, continuing investigation correlating such
      viscoelastic data with clinical symptoms may provide insight into the role played
      by iron in the setting of SCD, including complications such as vaso-occlusive
      crisis. 

PMID- 25986994
TI  - Can two dots form a Gestalt? Measuring emergent features with the capacity
      coefficient.
AB  - While there is widespread agreement among vision researchers on the importance of
      some local aspects of visual stimuli, such as hue and intensity, there is no
      general consensus on a full set of basic sources of information used in
      perceptual tasks or how they are processed. Gestalt theories place particular
      value on emergent features, which are based on the higher-order relationships
      among elements of a stimulus rather than local properties. Thus, arbitrating
      between different accounts of features is an important step in arbitrating
      between local and Gestalt theories of perception in general. In this paper, we
      present the capacity coefficient from Systems Factorial Technology (SFT) as a
      quantitative approach for formalizing and rigorously testing predictions made by
      local and Gestalt theories of features. As a simple, easily controlled domain for
      testing this approach, we focus on the local feature of location and the emergent
      features of Orientation and Proximity in a pair of dots. We introduce a redundant
      target change detection task to compare our capacity measure on (1) trials where
      the configuration of the dots changed along with their location against (2)
      trials where the amount of local location change was exactly the same, but there
      was no change in the configuration. Our results, in conjunction with our modeling
      tools, favor the Gestalt account of emergent features. We conclude by suggesting
      several candidate information-processing models that incorporate emergent
      features, which follow from our approach.

PMID- 25986993
TI  - Prognostic factors affecting the outcome of arthroscopic saucerization in discoid
      lateral meniscus: a retrospective analysis of 48 cases.
AB  - PURPOSE: The purpose of this retrospective study was to evaluate the results and
      prognostic factors affecting the outcome of arthroscopic saucerization for
      discoid lateral meniscus (DLM). METHODS: Forty-eight patients who underwent
      arthroscopic saucerization for DLM between January 2009 and January 2012 in two
      hospitals were included. There were 21 (43.8%) male and 27 (56.3%) female
      patients with a mean age of 36.02 +/- 14.5 (range 9-65) years at the time of
      operation. According to Watanabe classification, 33 (68.7%) patients had type II
      (incomplete) discoid meniscus and 15 (31.3%) had type I (complete) discoid
      meniscus. Of the 48 patients, 26 (54.2%) had an associated lateral meniscal tear.
      Seventeen patients (35.4%) had accompanying ligamentous, chondral and/or medial
      meniscal lesions. The symptoms were present for a mean of 8.04 +/- 4.48 (range 1
      24) months before the operation. All patients were followed up with a mean of
      27.7 +/- 10.7 (range 12-47) months using Lysholm knee score. We analyzed the
      relationship between the outcome variable (Lysholm knee score at the final follow
      up) and the predictor variables (age, gender, type of DLM, presence of meniscal
      tear, duration of symptoms, follow-up and accompanying intra-articular lesions).
      RESULTS: The mean preoperative Lysholm knee score was 46.6 +/- 10.2 points and
      increased to 85.08 +/- 13.45 points at the final follow-up (p = 0.0001). Twenty
      (41.7%) excellent, seven (14.6%) good, nineteen (39.6%) fair and two (4.2%) poor
      results have obtained. No complications were observed in any patient. Regression
      analysis showed that age was the only predictor of the Lysholm score at the final
      follow-up (R2 = 0.545, p = 0.0001). The linear regression equation was (Lysholm
      score at final follow-up) = 106.1 - [0.58 * (age of patient)]. CONCLUSIONS: This
      study demonstrated that arthroscopic saucerization is an effective and safe
      treatment modality for DLM. Furthermore, age of the patient was shown to be the
      most important prognostic factor over the final clinical outcome. An excellent or
      a good result can be expected when the patient is young at the time of operation.
      LEVEL OF EVIDENCE: IV.

PMID- 25986995
TI  - Predicting diabetic nephropathy by serum proteomic profiling in patients with
      type 2 diabetes.
AB  - PURPOSE: The purpose of this work is to examine the serum proteomic profiles
      associated with the subsequent development of diabetic nephropathy (DN) in
      patients with type 2 diabetes and to develop and validate a decision tree based
      on the profiles to predict the risk of DN in advance by albuminuria. METHODS:
      Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was
      used to obtain the proteomic profiles from baseline serum samples of 84 patients
      with type 2 diabetes with normal albuminuria, including 42 case subjects who
      developed DN after 4 years and 42 control subjects who remained normoalbuminuric
      over the same 4 years. From signatures of protein mass, a decision tree was
      established for predicting DN. RESULTS: At baseline, urinary albumin/creatinine
      ratio was similar between the case and control groups. The intensities of 5 peaks
      detected by CM10 chips appeared up-regulated, whereas 18 peaks were down
      regulated more than twofold in the case group than compared with the control
      group in the training set. An optimum discriminatory decision tree for case
      subjects created with four nodes using four distinct masses was challenged with
      testing set. The positive predictive value was 77.8% (7/9), and the negative
      predictive value was 72.7% (8/11). CONCLUSIONS: We developed and validated a
      decision tree to predict DN in patients with type 2 diabetes.

PMID- 25986996
TI  - Bevacizumab: an option for refractory epistaxis in hereditary haemorrhagic
      telangiectasia.
AB  - BACKGROUND: Recurrent epistaxis in hereditary haemorrhagic telangiectasia (HHT)
      patients significantly decreases their quality of life. Treatment in therapy
      refractory patients is limited although various options have been tested so far.
      CASE REPORT: Herein, one patient is described that was treated for HHT for over
      20 years with only intermediate benefits. As epistaxis duration and frequency
      increased continuously, bevacizumab 5 mg/kg was administered every 2 weeks.
      During the time of treatment (six doses) and up to 3 month afterwards clinical
      symptoms, blood pressure, cardiac output, pulmonary arterial hypertension (PAH),
      bleeding duration and frequency were assessed as criteria for treatment benefit.
      RESULTS: Duration and frequency of epistaxis decreased immediately after the
      first application resulting in reduced need of blood transfusions. After
      completion of six cycles, a further decrease in frequency and duration of
      bleeding was noted. Cardiac output and PAH decreased or remained stable,
      respectively, during time and after treatment. No increase in blood pressure
      could be found but a significant increase in heart rate was experienced after
      completion of all six applications. Unfortunately, the patient died due to a
      cerebral abscess. CONCLUSION: Bevacizumab led to an improvement of HHT related
      epistaxis, refractory to other treatments.

PMID- 25986997
TI  - Monogenic glucokinase diabetes and pregnancy: a case study.
AB  - It is estimated that up to 3 % of patients with gestational diabetes have
      glucokinase diabetes, termed also maturity-onset diabetes of the young type 2.
      The disorder has autosomal dominant inheritance. There is a 50 % risk of
      transmission of the gene to next generation. Two scenarios with different
      approach to the treatment may occur in pregnancy with glucokinase diabetes:
      either the fetus inherits the glucokinase mutation and the treatment of maternal
      hyperglycemia by insulin could increase the risk of fetal growth restriction, or
      the fetus is without glucokinase gene mutation and untreated hyperglycemia of the
      mother increases the risk of macrosomia and perinatal morbidity and insulin
      therapy is necessary. This article describes the outcome of two pregnancies in a
      patient with monogenic diabetes with glucokinase deficiency. A specific approach
      to the treatment is discussed.

PMID- 25986998
TI  - War and peace? The oncologic and the palliative care perspective on personalized
      cancer treatment in a patient with advanced cancer.
AB  - Personalized cancer treatment utilizing targeted therapies in a tailored approach
      is based on tumor and/or patient-specific molecular profiles. Recent clinical
      trials continue to look for new potential targets in heavily pretreated patients
      or rare disease entities. Careful selection of patients who may derive benefit
      from such therapies constitutes a challenge. This case report presents an
      experimental personalized cancer treatment in an advanced cancer patient and
      provides a list of issues for discussion: How can we combine treatment goals and
      simultaneously meet the individual needs in advanced cancer reconciling both
      perspectives: oncology and palliative care? 

PMID- 25986999
TI  - [Researcher of the month].

PMID- 25987000
TI  - Current pregnancy among women with spinal cord injury: findings from the US
      national spinal cord injury database.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To examine the prevalence of
      pregnancy and associations with sociodemographic and clinical factors among women
      with spinal cord injury (SCI). SETTING: US National Spinal Cord Injury Database,
      an SCI registry that interviews participants 1, 5 and then every 5 years post
      injury. Data include SCI clinical details, functional impairments, participation
      measures, depressive symptoms and life satisfaction. Women aged 18-49 are asked
      about hospitalizations in the last year relating to pregnancy or its
      complications. Data represent 1907 women, who completed 3054 interviews. METHODS:
      We used generalized estimating equations to examine bivariable associations
      between pregnancy and clinical and psychosocial variables and to perform
      multivariable regressions predicting pregnancy. RESULTS: Across all women, 2.0%
      reported pregnancy during the prior 12 months. This annual prevalence differed
      significantly by the years elapsed since injury; the highest rate occurred 15
      years post injury (3.7%). Bivariable analyses found that younger age at injury
      was significantly associated with current pregnancy (P<0.0001). Compared with
      nonpregnant women, those reporting current pregnancy were significantly more
      likely to be married or partnered, have sport-related SCI, have higher motor
      scores and have more positive psychosocial status scores. Multivariable analyses
      found significant associations between current pregnancy and age, marital status,
      motor score and mobility and occupation scale scores. CONCLUSION: Current
      pregnancy rates among reproductive-aged women with SCI are similar to rates of
      other US women with chronic mobility impairments. More information is needed
      about pregnancy experiences and outcomes to inform both women with SCI seeking
      childbearing and clinicians providing their care.

PMID- 25987001
TI  - Development, reliability and validity of the queensland evaluation of wheelchair
      skills (QEWS).
AB  - STUDY DESIGN: Psychometric studyObjectives:To develop and test a valid and
      reliable assessment of wheelchair skills for individuals with spinal cord
      injuries (SCI); the Queensland Evaluation of Wheelchair Skills (QEWS). SETTING:
      Hospital, Australia. METHODS: Phase 1: Four Delphi panel rounds with clinical
      experts were used to develop the QEWS. Phase 2: Intra-rater and inter-rater
      reliability of the QEWS items were examined in 100 people with SCI. Phase 3a:
      Concurrent validity was investigated by examining the association between QEWS
      total scores and physiotherapists' global ratings of wheelchair skill
      performance. Phase 3b: Construct validity was tested in 20 people with recent SCI
      by examining change in QEWS total scores between when they first mobilised in a
      wheelchair and scores obtained 10 weeks later. RESULTS: Phase 1: The QEWS was
      developed. Phase 2: The intra-class correlation coefficients reflecting the intra
      rater reliability and the inter-rater reliability for the QEWS total score were
      1.00 and 0.98, with scores being within one point of each other 96 and 91% of the
      time, respectively. Phase 3a: The QEWS total scores were comparable with the
      global rating of wheelchair skill performance (r2=0.93). Phase 3b: The QEWS
      scores changed by a median (interquartile range (IQR)) of 4 (1 to 6) points over
      the 10-week period following first wheelchair mobilisation. CONCLUSION: The QEWS
      is a valid and reliable tool for measuring wheelchair skills in individuals with
      SCI. The QEWS is efficient and practical to administer and does not require
      specialised equipment.

PMID- 25987002
TI  - Identifying physical activity type in manual wheelchair users with spinal cord
      injury by means of accelerometers.
AB  - STUDY DESIGN: This was a cross-sectional study. OBJECTIVES: The main objective of
      this study was to develop and test classification algorithms based on machine
      learning using accelerometers to identify the activity type performed by manual
      wheelchair users with spinal cord injury (SCI). SETTING: The study was conducted
      in the Physical Therapy department and the Physical Education and Sports
      department of the University of Valencia. METHODS: A total of 20 volunteers were
      asked to perform 10 physical activities, lying down, body transfers, moving
      items, mopping, working on a computer, watching TV, arm-ergometer exercises,
      passive propulsion, slow propulsion and fast propulsion, while fitted with four
      accelerometers placed on both wrists, chest and waist. The activities were
      grouped into five categories: sedentary, locomotion, housework, body transfers
      and moderate physical activity. Different machine learning algorithms were used
      to develop individual and group activity classifiers from the acceleration data
      for different combinations of number and position of the accelerometers. RESULTS:
      We found that although the accuracy of the classifiers for individual activities
      was moderate (55-72%), with higher values for a greater number of accelerometers,
      grouped activities were correctly classified in a high percentage of cases (83.2
      93.6%). CONCLUSIONS: With only two accelerometers and the quadratic discriminant
      analysis algorithm we achieved a reasonably accurate group activity recognition
      system (>90%). Such a system with the minimum of intervention would be a valuable
      tool for studying physical activity in individuals with SCI.

PMID- 25987003
TI  - Long-bone fractures in persons with spinal cord injury.
AB  - STUDY DESIGN: Retrospective data analysis. OBJECTIVES: To document fracture
      characteristics, management and related complications in individuals with
      traumatic spinal cord injury (SCI). SETTING: Rehabilitation centre for SCI
      individuals. METHOD: Patients' records were reviewed. Patients with traumatic SCI
      and extremity fractures that had occurred after SCI were included. Patient
      characteristics, fractured bone, fracture localisation, severity and management
      (operative/conservative), and fracture-related complications were extracted.
      RESULTS: A total of 156 long-bone fractures in 107 SCI patients (34 women and 73
      men) were identified. The majority of patients were paraplegics (77.6%) and
      classified as American Spinal Injury Association Impairment Scale A (86.0%). Only
      the lower extremities were affected, whereby the femur (60.9% of all fractures)
      was fractured more frequently than the lower leg (39.1%). A total of 70 patients
      (65.4%) had one fracture, whereas 37 patients (34.6%) had two or more fractures.
      Simple or extraarticular fractures were most common (75.0%). Overall, 130 (83.3%)
      fractures were managed operatively. Approximately half of the femur fractures
      (48.2%) were treated with locking compression plates. In the lower leg, fractures
      were mainly managed with external fixation (48.8%). Conservative fracture
      management was applied in 16.7% of the cases and consisted of braces or a well
      padded soft cast. Fracture-associated complications were present in 13.5% of the
      cases but did not differ significantly between operative (13.1%) and conservative
      (15.4%) fracture management. CONCLUSION: SCI was associated with simple or
      extraarticular fractures of the distal femur and the lower leg. Fractures were
      mainly managed operatively with a low complication rate.

PMID- 25987005
TI  - Microwave Spectrum of Hexafluoroisopropanol and Torsional Behavior of Molecules
      with a CF3-C-CF3 Group.
AB  - This paper presents the first microwave spectroscopic investigation on
      hexafluoroisopropanol (HFIP). A pulsed nozzle Fourier transform microwave
      spectrometer has been used to determine the rotational constants for HFIP as A =
      2105.12166(18) MHz, B = 1053.99503(12) MHz, and C = 932.33959(13) MHz. In
      addition, five isotopologues of HFIP have been observed experimentally to
      determine the accurate structure of HFIP. The observed spectrum could be assigned
      to the most stable conformer of HFIP, called antiperiplanar. Available
      spectroscopic information and ab initio calculations on five prototype molecules
      helped in exploring the torsional behavior of molecules having a CF3-C-CF3 group.
      Two-dimensional potential energy surfaces have been analyzed for all molecules,
      which explained the presence/absence of doubling in the rotational transitions.
      With the help of natural bond orbital (NBO) analysis, reasons for the
      conformational preference of HFIP have been explained. 

PMID- 25987004
TI  - Review of dietetic service provision and activity in spinal cord injury centres:
      a multicentre survey in the UK and Republic of Ireland.
AB  - OBJECTIVES: The present study was undertaken to review the service provision in
      spinal cord injury (SCI) centres (SCICs); to establish and compare how much time
      dietitians spend in direct and indirect contact with patients; and to document
      current nutritional screening practices. METHODS: All 12 SCICs in the United
      Kingdom and the Republic of Ireland were surveyed by a postal questionnaire in
      April 2014. Data collected included the number of whole-time-equivalent (WTE)
      staff available, whether a nutrition team was present and the use of nutrition
      screening tools. A work sampling tool was used to capture dietetic activity for a
      period of 1 week. RESULTS: Eight (66.7%) SCICs responded (390/531 of total SCI
      beds) and the average numbers of patients per WTE staff, including consultants,
      nurses, dietitians, physiotherapists, occupational therapists were recorded. Six
      out of eight SCICs used a validated nutritional screening tool. Thirty-two work
      sampling tools were analysed, revealing that spinal dietitians spend 39.1% of the
      working day in direct patient-related activities. Staffing levels varied and were
      below clinical recommendations in six out of eight SCICs. CONCLUSION: The
      resources allocated to nutritional care in SCICs appear to be varied and limited.
      This suggests malnutrition may continue to be under-recognised and under-treated.
      To address the complex nutritional needs of this special population group there
      is a clear need to establish staffing level for dietitians. Information collected
      from the present study could contribute to the supply analysis of a future
      workforce planning exercise in SCIC dietetic service.

PMID- 25987006
TI  - A rare case of multiple sclerosis and McArdle disease.

PMID- 25987007
TI  - Development of digestive tract and enzyme activities during the early ontogeny of
      the tropical gar Atractosteus tropicus.
AB  - Changes in digestive enzyme activity and histology were studied in Atractosteus
      tropicus embryos, larvae and juvenile periods. Alkaline protease, chymotrypsin,
      carboxypeptidase A, lipase and alpha-amylase were detected in all periods and
      gradually increased until reaching the maximum peak in juveniles; meanwhile, acid
      protease was first detected at 5 days after hatching (dah) when first feeding
      started and trypsin and leucine aminopeptidase activities were detected from 19
      dah, their values being increased gradually until reaching a maximum value at 31
      dah. Acid and alkaline phosphatase activities increased from yolk-sac absorption
      (3 dah) until day 31 after hatching. Zymogram for acid protease showed two bands
      in active forms (0.4 and 0.5 Rfs) from day 5 after hatching and a third protease
      form (0.3 Rf) that appears at 31 dah. Two active forms (26.3 and 24.9 kDa) were
      detected using SDS-PAGE alkaline proteases zymogram at 5 dah, and an additional
      active form (44.1 kDa) was detected at 7 dah. Regarding the histological
      development of the digestive system, the exocrine pancreas containing zymogen
      granules was already visible at 3 dah, whereas at 5 dah first gastric glands were
      already detected in the stomach. Between 7 and 9 dah, the digestive tract of A.
      tropicus resembled that of a juvenile specimen with a well-developed and short
      oesophagus, stomach divided into a glandular and non-glandular (pyloric) stomach,
      folded intestine with pyloric caeca and a well-developed spiral valve (posterior
      intestine). Considering this, larvae of A. tropicus are capable of digesting
      several foods from yolk absorption (3 dah), maximizing its activities at 15 dah,
      age at which the organisms maximize its capability to absorb nutrients from diets
      provided. 

PMID- 25987009
TI  - Current trends and recent advances in diagnosis, therapy, and prevention of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors
      worldwide and its associated morbidity and mortality remain of significant
      concern. Based on in-depth reviews of serological diagnosis of HCC, in addition
      to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP
      L3), des- carboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth
      factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3
      (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell
      carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection
      of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging
      methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT)
      and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl
      enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the
      promising imaging madalities of choice. With regard to recent advancements in
      tissue markers, many cuting-edge technologies using genome-wide DNA microarrays,
      qRT-PCR, and proteomic and inmunostaining studies have been implemented in an
      attempt to identify markers for early diagnosis of HCC. Only less than half of
      HCC patients at initial diagnosis are at an early stage treatable with curative
      options: local ablation, surgical resection, or liver transplant. Transarterial
      chemoembolization (TACE) is considered the standard of care with palliation for
      intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and
      radioembolization using Yttrium-90 may exhibit beneficial effects in HCC
      treatment. During the past few years, several molecular targeted agents have been
      evaluated in clinical trials in advanced HCC. Sorafenib is currently the only
      approved systemic treatment for HCC. It has been approved for the therapy of
      asymptomatic HCC patients with well-preserved liver function who are not
      candidates for potentially curative treatments, such as surgical resection or
      liver transplantation. In the USA, Europe and particularly Japan, hepatitis C
      virus (HCV) related HCC accounts for most liver cancer, as compared with Asia
      Pacific regions, where hepatitis B virus (HBV) may play a more important role in
      HCC development. HBV vaccination, while a vaccine is not yet available against
      HCV, has been recognized as a best primary prevention method for HBV-related HCC,
      although in patients already infected with HBV or HCV, secondary prevention with
      antiviral therapy is still a reasonable strategy. In addition to HBV and HCV,
      attention should be paid to other relevant HCC risk factors, including
      nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol
      consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin
      K2 have been proven to provide protective effects against HCC. Regarding tertiary
      prevention of HCC recurrence after surgical resection, addition of antiviral
      treatment has proven to be a rational strategy. 

PMID- 25987010
TI  - Types of Cancers Prevailing in Pakistan and their Management Evaluation.
AB  - Cancer is basically a class of disorder marked by uncontrolled proliferation of
      cells which have the potential to interfere with different systems of body like
      digestive, central nervous and circulatory systems by releasing hormones. Tumors
      that reside only in a specified location and show restricted growth are commonly
      characterized as benign tumors. When tumor cells grow and effectively spread to
      other body parts and potentially invade and damage healthy tissues they show
      various degrees of malignancy. Cancer may be caused by different factors like
      gene mutations, carcinogens and some medical factors that harm the immune system
      of the body. Symptoms of cancer are relatively varied and classified according to
      location, progression pattern and size of tumors as well. Different diagnostic
      tests are used for evaluation that depends on the type of cancer. Cancer
      management and chemo protocols also depend on the progression and site where it
      develops. Cancers like breast, lung, liver, colorectal, prostate, head and neck
      carcinoma are most commonly diagnosed in Pakistan. This review briefly describes
      the three most common cancers prevailing in Pakistan and their management
      evaluation. 

PMID- 25987008
TI  - Digestive system development and study of acid and alkaline protease digestive
      capacities using biochemical and molecular approaches in totoaba (Totoaba
      macdonaldi) larvae.
AB  - The present study aimed to describe and understand the development of the
      digestive system in totoaba (Totoaba macdonaldi) larvae from hatching to 40 days
      post-hatch (dph) from morphological and functional perspectives. At hatch, the
      digestive system of totoaba was undifferentiated. The anus and the mouth opened
      at 4 and 5 dph, respectively. During exogenous feeding, development of the
      esophagus, pancreas, liver and intestine was observed with a complete
      differentiation of all digestive organs. Expression and activity of trypsin and
      chymotrypsin were observed as early as at 1 dph, and increments in their
      expression and activity coincided with changes in food items (live and compound
      diets) and morpho-physiological development of the accessory digestive glands. In
      contrast, pepsin was detected later during development, which includes the
      appearance of the gastric glands between 24 and 28 dph. One peak in gene
      expression was detected at 16 dph, few days before the initial development of the
      stomach at 20 dph. A second peak of pepsin expression was detected at day 35,
      followed by a peak of activity at day 40, coinciding with the change from live to
      artificial food. Totoaba larvae showed a fully morphologically developed
      digestive system between 24 and 28 dph, as demonstrated by histological
      observations. However, gene expression and activity of alkaline and acid
      proteases were detected earlier, indicating the functionality of the exocrine
      pancreas and stomach before the complete morphological development of the
      digestive organs. These results showed that integrative studies are needed to
      fully understand the development of the digestive system from a morphological and
      functional point of views, since the histological organization of digestive
      structures does not reflect their real functionality. These results indicate that
      the digestive system of totoaba develops rapidly during the first days post
      hatch, especially for alkaline proteases, and the stomach becomes functional
      between 20 and 24 dph allowing the weaning process to begin at this age. 

PMID- 25987011
TI  - Update knowledge on cervical cancer incidence and prevalence in Asia.
AB  - Cervical cancer is the second most common cause of cancer-related death among
      women worldwide, with over 500,000 new cases diagnosed annually and 50% mortality
      rate in Asia. In the United States, approximately 10,370 new cases of cervical
      cancer are diagnosed annually, and estimated 3,710 deaths occur from the disease,
      making it the sixth most common cause of malignancy among American women. This
      study aims to provide awareness about cervical cancer as well as an updated
      knowledge about the prevalence and incidence of cervical cancer in Asia. 

PMID- 25987012
TI  - Associations of Probiotics with Vitamin D and Leptin Receptors and their Effects
      on Colon Cancer.
AB  - Colorectal cancer (CRC) is one of most common causes of cancer-related death
      worldwide. Recent studies have suggested that microbial and environmental factors
      including diet and lifestyle can impact on colon cancer development. Vitamin D
      deficiency and dysfunction of vitamin D receptor (VDR) also correlate with colon
      cancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of
      food intake and is associated with other environmental factors affecting colon
      cancer through the leptin receptor. Altered levels of serum leptin and patterns
      of expression of its receptor (LPR) may be observed in human colon tumours.
      Furthermore, the collected data from in vitro and in vivo studies have indicated
      that consuming probiotic non-pathogenic lactic acid bacteria have beneficial
      effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have been
      correlated with leptin and its receptor and are also with colon cancer. Thus, in
      this paper, we review recent progress on the roles of probiotic, vitamin D/VDR
      and leptin/LPR in inflammation and colon cancer. 

PMID- 25987013
TI  - Emerging roles of Kruppel-like factor 4 in cancer and cancer stem cells.
AB  - Cancer stem cells (CSCs) are rare subpopulations within tumors which are
      recognized as culprits in cancer recurrence, drug resistance and metastasis.
      However, the molecular mechanisms of how CSCs are regulated remain elusive.
      Kruppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing
      transcription factors with diverse functions in cell differentiation,
      proliferation, embryogenesis and pluripotency. Recent progress has highlighted
      the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for
      better therapeutics of cancer disease, it is crucial to develop a deeper
      understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we
      summarized the current understanding of the transcriptional regulation of KLF4 in
      CSCs, and discussed the functional implications of targeting CSCs for potential
      cancer therapeutics. 

PMID- 25987014
TI  - Tumor infiltrating lymphocytes in ovarian cancer.
AB  - Several improvements in ovarian cancer treatment have been achieved in recent
      years, both in surgery and in combination chemotherapy with targeting. However,
      ovarian tumors remain the women's cancers with highest mortality rates. In this
      scenario, a pivotal role has been endorsed to the immunological environment and
      to the immunological mechanisms involved in ovarian cancer behavior. Recent
      evidence suggests a loss of the critical balance between immune-activating and
      immune-suppressing mechanisms when oncogenesis and cancer progression occur.
      Ovarian cancer generates a mechanism to escape the immune system by producing a
      highly suppressive environment. Immune-activated tumor infiltrating lymphocytes
      (TILs) in ovarian tumor tissue testify that the immune system is the trigger in
      this neoplasm. The TIL mileau has been demonstrated to be associated with better
      prognosis, more chemosensitivity, and more cases of optimal residual tumor
      achieved during primary cytoreduction. Nowadays, scientists are focusing
      attention on new immunologically effective tumor biomarkers in order to optimize
      selection of patients for recruitment in clinical trials and to identify
      relationships of these biomarkers with responses to immunotherapeutics. Assessing
      this point of view, TILs might be considered as a potent predictive immunotherapy
      biomarker. 

PMID- 25987015
TI  - Using implementation science to advance cancer prevention in India.
AB  - Oral, cervical and breast cancers, which are either preventable and/or amenable
      to early detection and treatment, are the leading causes of cancer-related
      morbidity and mortality in India. In this paper, we describe implementation
      science research priorities to catalyze the prevention and control of these
      cancers in India. Research priorities were organized using a framework based on
      the implementation science literature and the World Health Organization's
      definition of health systems. They addressed both community-level as well as
      health systems-level issues. Community-level or "pull" priorities included the
      need to identify effective strategies to raise public awareness and understanding
      of cancer prevention, monitor knowledge levels, and address fear and stigma.
      Health systems-level or "push" and "infrastructure" priorities included
      dissemination of evidence- based practices, testing of point-of-care technologies
      for screening and diagnosis, identification of appropriate service delivery and
      financing models, and assessment of strategies to enhance the health workforce.
      Given the extent of available evidence, it is critical that cancer prevention and
      treatment efforts in India are accelerated. Implementation science research can
      generate critical insights and evidence to inform this acceleration. 

PMID- 25987016
TI  - Genetic Association between the XPG Asp1104His Polymorphism and Head and Neck
      Cancer Susceptibility: Evidence Based on a Meta-Analysis.
AB  - BACKGROUND: Previous studies evaluating the association between the xeroderma
      pigmentosum group G (XPG) Asp1104His polymorphism and head and neck cancer
      susceptibility have proven controversial. This meta-analysis of the literature
      was performed to obtain a more precise estimation of the relationship. MATERIALS
      AND METHODS: We systematically searched PubMed, Embase and Web of Science with a
      time limit of Dec 18, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs)
      were used to assess the strength of any association. RESULTS: We performed a meta
      analysis of eight published case-control studies, including 3,621 cases and 5,475
      controls. Overall, no significant association was found between the XPG
      Asp1104His polymorphism and head and neck cancer susceptibility under all genetic
      models. In the subgroup analysis by ethnicity, the XPG Asp1104His polymorphism
      had statistically significant association with elevated head and neck cancer risk
      under CC vs GG (OR=1.24, 95% CI=1.00~1.54) and the recessive model (OR=1.22,
      95%CI=1.01~1.46) in Asian populations. A similar result was found under CC vs GG
      (OR =1.22, 95%CI =1.01~1.47) in the population based subgroup by source of
      control. When performed by tumor site, the XPG Asp1104His polymorphism had
      statistically significant association with elevated laryngeal cancer under all
      genetic models (CC vs GG: OR=1.59, 95% CI=1.16~2.19; GC vs GG: OR=1.38,
      95%CI=1.10~1.72; dominant model: OR=1.42, 95% CI=1.15~1.74; recessive model:
      OR=1.36, 95% CI=1.02~1.81). CONCLUSIONS: This meta-analysis suggested that the
      XPG Asp1104His polymorphism is a risk factor for head and neck cancer
      susceptibility, especially for laryngeal cancer and in Asian populations.

PMID- 25987017
TI  - Health Screening among HBV Carriers in the Korean National Health and Nutrition
      Examination Survey V (KNHANES V).
AB  - We aimed to investigate the differences in health screening, including medical
      checkups and cancer screening, between HBV carriers and non-carriers in the
      Republic of Korea. In the fifth Korean National Health and Nutrition Examination
      Survey (KNHANES V), conducted between 2010 and 2012, 17,865 persons who answered
      regarding their HBV-infection status, medical checkup history, liver cancer
      screening and general cancer screening within the past years were included in the
      final analysis. In total, 295 persons were HBV carriers. Logistic regression
      models were used to compare the health check-up rate between the HBV carriers and
      non- HBV carriers. The HBV carriers were more likely to have been screened for
      liver cancer [adjusted odds ratio (OR): 2.83, 95% confidence interval (95%CI):
      1.90-4.21] or cancer [OR: 1.44, 95%CI: 1.04-1.99]. The HBV carriers showed a
      probability of receiving medical checkups that was identical to that of the non
      carriers [OR: 0.99, 95%CI: 0.72-1.35]. The HBV carriers, who were at higher risk
      of developing chronic liver disease, were more likely to be screened for cancer,
      including liver cancer, than the non-HBV carriers; no difference in the rate of
      medical checkups was observed between the HBV carriers and non-HBV carriers. 

PMID- 25987018
TI  - Systematic review on international practices in controlling waterpipe tobacco
      smoking.
AB  - BACKGROUND: Waterpipe tobacco smoking has becoming popular especially among young
      people worldwide. Smokers are attracted by its sweeter, smoother smoke, social
      ambience and the misconception of reduced harm. The objective of this study was
      to systematically review the effects of waterpipe tobacco policies and practices
      in reducing its prevalence. MATERIALS AND METHODS: A systematic review was
      conducted electronically using the PubMed, OVID, Science Direct, Proquest and
      Embase databases. All possible studies from 1980 to 2013 were initially screened
      based on titles and abstracts. The selected articles were subjected to data
      extraction and quality rating. RESULTS: Three studies met the inclusion criteria
      and were eligible for this review. Almost all of the waterpipe tobacco products
      and its accessories did not comply with the regulations on health warning
      labelling practices as stipulated under Article 11 of WHO FCTC. In addition, the
      grisly new warning labels for cigarettes introduced by Food and Drug
      Administration did not affect hookah tobacco smoking generally. Indoor air
      quality in smoking lounges was found to be poor and some hookah lounges were
      operated without smoke shop certification. CONCLUSIONS: Our findings revealed the
      availability of minimal information on the practices in controlling waterpipe
      smoking in reducing its prevalence. The lack of comprehensive legislations or
      practices in controlling waterpipe smoking warrants further research and policy
      initiatives to curb this burgeoning global epidemic, especially among the
      vulnerable younger population.

PMID- 25987019
TI  - PU.1 Is Identified as a Novel Metastasis Suppressor in Hepatocellular Carcinoma
      Regulating the miR-615-5p/IGF2 Axis.
AB  - Invasion and metastasis is the major cause of tumor recurrence, difficulty for
      cure and low survival rate. Excavating key transcription factors, which can
      regulate tumor invasion and metastasis, are crucial to the development of
      therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription
      factor and a vital regulator in life. Here, we report that, compared to adjacent
      non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular
      carcinoma (HCC), but not primary HCC, was significantly down-regulated. In
      addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and
      MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion
      assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell
      lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of
      PU.1 suppressed the invasion of these cells. However, knockdown and
      overexpression of PU.1 did not influence proliferation. Finally, we tried to
      explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP
      qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p
      promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre
      and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene
      IGF2. These data indicate that PU.1 inhibits invasion of human HCC through
      promoting miR-615-5p and suppressing IGF2. These findings improve our
      understanding of PU.1 regulatory roles and provided a potential target for
      metastatic HCC diagnosis and therapy. 

PMID- 25987020
TI  - Characteristic Trend Analysis of Cancer Patients Hospitalized in Shanxi Tumor
      Hospital for the First Time during 2001 and 2010.
AB  - To observe and analyze the characteristic trend of cancer patients hospitalized
      for the first time in Shanxi Tumor Hospital from 2001 to 2010, clinical data
      including case number, age, gender, and frequency of different tumor occurrences
      were collected and statistically analyzed. RESULTS: (i) From 2001 to 2010, the
      number of cancer patients hospitalized for the first time increased by 1.3-fold;
      (ii) The patient overall average age also increased from 51.8 to 54.4, for males
      from 55.5 to 58.7 and females from 48.4 to 51.1, respectively. (iii) Male
      patients accounted for 43-48% and females accounted for 52-57% of the total. The
      percentage of female patients was higher than that of male patients in every year
      and showed an upward trend over the years, while that of the males showed a
      downward trend (chi2 =7.031, p=0.008); (iv) Among the top 6 most common cancers,
      lung, cervical, esophageal, colorectal and breast cancers tended to increase over
      the years (p<0.05), but not gastric cancer (p=0.423). CONCLUSIONS: (i) The number
      of cancer patients hospitalized for the first time during the past 10 years
      increased year by year, and was higher for female than male; (ii) the average age
      of patients increased year after year and was greater for male than female; (iii)
      the number of patients with lung cancer, cervical cancer, esophageal cancer,
      colorectal cancer and breast cancer increased over years.

PMID- 25987021
TI  - Regulatory Network of MicroRNAs, Host Genes, Target Genes and Transcription
      Factors in Human Esophageal Squamous Cell Carcinoma.
AB  - Abnormally expressed microRNAs (miRNAs) and genes have been found to play key
      roles in esophageal squamous cell carcinoma (ESCC), but little is known about the
      underlying mechanisms. The aim of this paper was to assess inter-relationships
      and the regulatory mechanisms of ESCC through a network-based approach. We built
      three regulatory networks: an abnormally expressed network, a related network and
      a global network. Unlike previous examples, containing information only on genes
      or miRNAs, the prime focus was on relationships. It is worth noting that
      abnormally expressed network emerged as a fault map of ESCC. Theoretically, ESCC
      might be treated and prevented by correcting the included errors. In addition,
      the predicted transcription factors (TFs) obtained by the P-match method also
      warrant further study. Our results may further guide gene therapy researchers in
      the study of ESCC. 

PMID- 25987022
TI  - No increase in breast cancer risk in Japanese women taking oral contraceptives: a
      case-control study investigating reproductive, menstrual and familial risk
      factors for breast cancer.
AB  - BACKGROUND: Low-dose oral contraceptives (OC) were approved by the Japanese
      Ministry of Health, Labor and Welfare in 1999, yet despite their contraceptive
      and non-contraceptive health benefits, only 5% of the target population use them.
      Fear of increased cancer risk, particularly breast cancer, is one reason for
      this. Due to low OC uptake and low screening participation, a paucity of data is
      available on the risk of OC use and breast cancer in Japanese women. The present
      study investigated OC use and breast cancer risk, as well as menstrual,
      reproductive and family factors. MATERIALS AND METHODS: This was a clinic-based
      case-control study of women aged 20-69yrs who had undergone breast screening
      between January 2007 and December 2013 in central Tokyo. In all, 28.8% of the
      participants had experience with OC use. Cases were 155 women with a
      pathologically confirmed diagnosis of breast cancer. Controls were the remaining
      12,333 women. RESULTS: Increased age was a significant risk factor for breast
      cancer (p<0.001). A lower risk was found in premenopausal women presently taking
      OC compared to never users (OR 0.45; 95% CI 0.22-0.90) after adjusting for age,
      parity and breast feeding, and a family history of breast cancer. CONCLUSIONS:
      Increased age rather than OC use had a greater effect on breast cancer risk. This
      risk may be decreased in premenopausal women with OC use, but further long-term
      prospective studies are necessary.

PMID- 25987023
TI  - Comparative proteomics and global genome-wide expression data implicate role of
      ARMC8 in lung cancer.
AB  - BACKGROUND: Cancer loci comprise heterogeneous cell populations with diverse
      cellular secretions. Therefore, disseminating cancer-specific or cancer
      associated protein antigens from tissue lysates could only be marginally correct,
      if otherwise not validated against precise standards. MATERIALS AND METHODS: In
      this study, 2DE proteomic profiles were examined from lysates of 13 lung
      adenocarcinoma tissue samples and matched against the A549 cell line proteome.
      A549 matched-cancer-specific hits were analyzed and characterized by MALDI
      TOF/MS. RESULTS: Comparative analysis identified a total of 13 protein spots with
      differential expression. These proteins were found to be involved in critical
      cellular functions regulating pyrimidine metabolism, pentose phosphate pathway
      and integrin signaling. Gene ontology based analysis classified majority of
      protein hits responsible for metabolic processes. Among these, only a single non
      predictive protein spot was found to be a cancer cell specific hit, identified as
      Armadillo repeat-containing protein 8 (ARMC8). Pathway reconstruction studies
      showed that ARMC8 lies at the centre of cancer metabolic pathways. CONCLUSIONS:
      The findings in this report are suggestive of a regulatory role of ARMC8 in
      control of proliferation and differentiation in lung adenocarcinomas.

PMID- 25987024
TI  - High Expression of Matrix Metalloproteinase-11 indicates Poor Prognosis in Human
      Cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma (CHCA) is serious public health problem in
      Thailand, especially in the northeastern and northern regions. CHCA is known as
      one of the most aggressive malignant tumors associated with local invasion and a
      high rate of metastasis. A crucial step in the invasion process is the
      proteolytic degradation of the extracellular matrix (ECM) and basal membranes,
      for which several studies have shown a critical role played by matrix
      metalloproteinase-11 (MMP-11). OBJECTIVE: This study aim to detect MMP-11
      expression in CHCA specimens and any correlation with survival time. MATERIALS
      AND METHODS: A retrospective analysis was conducted of 30 patients with CHCA in
      Rajvithi hospital, who had undergone immunohistochemical staining of MMP-11.
      Relationships between clinicopathological data and MMP-11 expression in CHCA
      specimens were analyzed by the chi2 test or Fisher's exact test. The estimated
      survival and the survival differences were analyzed by the Kaplan-Meier method
      and the log-rank test, respectively. RESULTS: MMP-11 expression was found in 15
      specimens (50%). The overall mean survival time is 237.0 days (95% CI 135.4
      338.5, SD 271.9). Specimens with a positive MMP-11 had an average survival time
      of 136.7 days (95%CI 50.3-223.1, SD 156.0). Survival differences was signficant
      for the positive and negative MMP-11(p=0.022), but not well differentiated tumor
      and moderate to poor differentiated tumor (p=0.755), CA19-9 level of >1,000 and
      <1,000 (p=0.488), and between advanced and non-advanced staging (p=0.388).
      CONCLUSIONS: The positive MMP-11 expression indicates poor prognosis in CHCA
      specimens.

PMID- 25987025
TI  - Preoperative Neutrophil to Lymphocyte Ratio as a Prognostic Factor in Patients
      with Non-metastatic Renal Cell Carcinoma.
AB  - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of
      mortality in patients with colorectal, lung, gastric cancer, pancreatic and
      metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an
      independent prognostic factor for non-metastatic renal cell carcinoma (RCC).
      MATERIALS AND METHODS: Data from 327 patients who underwent curative or
      palliative nephrectomy were evaluated retrospectively. In preoperative blood
      routine examination, neutrophils and lymphocytes were obtained. The predictive
      value of NLR for non-metastatic RCC was analyzed. RESULTS: The NLR of 327
      patients was 2.72+/-2.25. NLR <1.7 and NLR >=1.7 were classified as low and high
      NLR groups, respectively. Chi-square test showed that the preoperative NLR was
      significantly correlated with the tumor size (P=0.025), but not with the
      histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS)
      and disease-free survival (DFS) were assessed using the Kaplan-Meier method.
      Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate
      the independent prognostic significance of NLR, multivariate COX regression
      models were applied and identified increased NLR as an independent prognostic
      factor for OS (P=0.015), and DFS (P=0.019). CONCLUSIONS: Regarding patient
      survival, an increased NLR represented an independent risk factor, which might
      reflect a higher risk for severe cardiovascular and other comorbidities. An
      elevated blood NLR may be a biomarker of poor OS and DFS in patients with non
      metastatic RCC.

PMID- 25987026
TI  - Clinicopathologic and Prognostic Significance of Carboxyl Terminus of Hsp70
      interacting Protein in HBV-related Hepatocellular Carcinoma.
AB  - BACKGROUND: Many factors, including molecular ones, were demonstrated to be
      associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far,
      the expression and clinicopathologic and prognostic significance of the carboxyl
      terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)-
      related HCC remain unknown. MATERIALS AND METHODS: CHIP expression was detected
      by immunohistochemical staining of surgical samples from 79 patients with HCC
      with HBsAg positivity. In addition, correlations with clinicopathologic
      parameters and patient survival were evaluated. RESULTS: It was found that
      positive CHIP staining was observed in tumor, but not non-tumor, tissues. High
      expression of CHIP was significantly related to larger tumor size, with
      marginally significant associations noted for presence of portal vein invasion
      and higher serum a-fetoprotein level. In addition, univariate analysis showed
      that high CHIP expression was a powerful predictor for dismal overall and disease
      free survival. However, independent prognostic implications of CHIP were not
      proven in multivariate Cox regression test. CONCLUSIONS: CHIP is overexpressed in
      HBV-related HCC and is associated with unfavorable biological behavior as well as
      poor prognosis. However, its prognostic role needs to be further validated.

PMID- 25987027
TI  - Angelica sinensis polysaccharide induces erythroid differentiation of human
      chronic myelogenous leukemia k562 cells.
AB  - Leukemia is a clonal disorder with blocked normal differentiation and cell death
      of hematopoietic progenitor cells. Traditional modalities with most used
      radiation and chemotherapy are nonspecific and toxic which cause adverse effects
      on normal cells. Differentiation inducing therapy forcing malignant cells to
      undergo terminal differentiation has been proven to be a promising strategy.
      However, there is still scarce of potent differentiation inducing agents. We show
      here that Angelica sinensis polysaccharide (ASP), a major active component in
      Dong quai (Chinese Angelica sinensis), has potential differentiation inducing
      activity in human chronic erythro- megakaryoblastic leukemia K562 cells. MTT
      assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell
      proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered
      K562 cells to undergo erythroid differentiaton as revealed by morphological
      changes, intensive benzidine staining and hemoglobin colorimetric reaction, as
      well as increased expression of glycophorin A (GPA) protein. ASP induced
      redistribution of STAT5 protein from the cytoplasm to the nucleus. Western
      blotting analysis further identified that ASP markedly sensitized K562 cells to
      exogenous erythropoietin (EPO) by activating EPO-induced JAK2/ STAT5 tyrosine
      phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway.
      On the basis of these findings, we propose that ASP might be developed as a
      potential candidate for chronic myelogenous leukemia inducing differentiation
      treatment. 

PMID- 25987028
TI  - UBE2Q1 in a Human Breast Carcinoma Cell Line: Overexpression and Interaction with
      p53.
AB  - The p53 tumor suppressor protein is a principal mediator of growth arrest,
      senescence, and apoptosis in response to a broad array of cellular damage. p53 is
      a substrate for the ubiquitin-proteasome system, however, the ubiquitin
      conjugating enzymes (E2s) involved in p53 ubiquitination have not been well
      studied. UBE2Q1 is a novel E2 ubiquitin conjugating enzyme gene. Here, we
      investigated the effect of UBE2Q1 overexpression on the level of p53 in the MDA
      MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53.
      By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB
      468, was transfected with the vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western
      blot analysis was employed to verify the overexpression of UBE2Q1 in MDA-MB-468
      cells and to evaluate the expression level of p53 before and after cell
      transfection. Immunoprecipitation and GST pull-down protocols were used to
      investigate the binding of UBE2Q1 to p53. We established MDA-MB-468 cells that
      transiently expressed a GFP fusion proteins containing UBE2Q1 (GFP-UBE2Q1).
      Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1
      transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in
      vivo and in vitro data showed that UBE2Q1 co-precipitated with p53 protein. Our
      data for the first time showed that overexpression of UBE2Q1can lead to the
      repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to its
      UBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process
      that may involve direct interaction of UBE2Q1with p53. 

PMID- 25987029
TI  - Personal and socio-cultural barriers to cervical cancer screening in Iran,
      patient and provider perceptions: a qualitative study.
AB  - BACKGROUND: Although cervical cancer is preventable and early screening might
      decrease the associated mortality, challenges faced by the women and health care
      providers can postpone early detection. This qualitative study aimed to establish
      patient and provider perceptions about personal and socio-cultural barriers for
      cervical cancer screening in Mashhad, Iran. MATERIALS AND METHODS: In the present
      study, which was conducted in 2012, eighteen participants, who were selected
      purposefully, participated in individual in-depth, semi-structured interviews,
      which were recorded, transcribed verbatim, and analyzed using conventional
      content analysis and Atlas-Ti software. RESULTS: One theme and two categories
      were derived from data including: cognitive/behavioral factors (lack of a
      community-based approach to cervical cancer, lack of awareness, wrong attitude
      and lack of health seeking behaviors) and socio/cultural issues (socio-cultural
      invasion, mismatch between tradition, modernity and religious, extra marital
      relationships and cultural taboos). CONCLUSIONS: Providing community based
      approach education programs and employing social policy are needed for preventing
      of cervical cancer in Iran.

PMID- 25987030
TI  - Insulin-like Growth Factor-1, IGF-binding Protein-3, C-peptide and Colorectal
      Cancer: a Case-control Study.
AB  - CONTEXT: Insulin-like growth factor peptides play important roles in regulating
      cell growth, cell differentiation, and apoptosis, and have been demonstrated to
      promote the development of colorectal cancer (CRC). OBJECTIVE: To examine the
      association of insulin-related biomarkers including insulin-like growth factor-1
      (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide
      with CRC risk and assess their relevance in predictive models. MATERIALS AND
      METHODS: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3
      and C-peptide were estimated using unconditional logistic regression models in
      100 colorectal cancer cases and 100 control subjects. Areas under the receiving
      curve (AUC) and integrated discrimination improvement (IDI) statistics were used
      to assess the discriminatory potential of the models. RESULTS: Serum levels of
      IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk
      (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for
      trend <.01 respectively) and serum C-peptide was positively associated with risk
      of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to
      the risk model, prediction for the risk of colorectal cancer had substantially
      improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C
      peptide were simultaneously included inthe reference model [P for AUC improvement
      was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)].
      CONCLUSIONS: The results provide evidence for an association of insulin-related
      biomarkers with colorectal cancer risk and point to consideration as candidate
      predictor markers.

PMID- 25987031
TI  - Radiotherapy Alone is Associated with Improved Outcomes Over Surgery in the
      Management of Solitary Plasmacytoma.
AB  - BACKGROUND: A moderate dose of radiation is the recommended treatment for
      solitary plasmacytoma (SP), but there is controversy over the role of surgery.
      Our study aimed at comparing different treatment modalities in the management of
      SP. MATERIALS AND METHODS: Data from 38 consecutive patients with solitary
      plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary
      plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy
      alone; 11 received surgery alone, and 12 received both. The median radiation dose
      was 50Gy. All operations were performed as radical resections. Local progression
      free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free
      survival (PFS) and overall survival (OS) were calculated and outcomes of
      different therapies were compared. RESULTS: The median follow-up time was 55
      months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%,
      respectively. Univariate analysis revealed, compared with surgery alone,
      radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs
      69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and
      OS (100% vs 70%, p=0.041). CONCLUSIONS: Radiotherapy alone can be considered as a
      more effective treatment for SP over surgery. Whether a combination of
      radiotherapy and surgery improves outcomes requires further study.

PMID- 25987032
TI  - Dietary fibre and the risk of colorectal cancer: a case- control study.
AB  - BACKGROUND: Colorectal cancer is one of the most commonly occurring cancers in
      China. Dietary fibre has been thought to decrease the risk of colorectal cancer
      in Western countries. However, studies investigating the association between
      dietary fibre (particularly soluble and insoluble fibres) and colorectal cancer
      have hitherto been lacking in China. OBJECTIVE: This case-control study examined
      the effect of dietary fibre intake on the risk of colorectal cancer, stratified
      by tumour site. MATERIALS AND METHODS: The study included 265 cases (colon
      cancer, 105; rectal cancer, 144; colon and rectal cancer, 16) and 252 controls
      residing in Qingdao. A food frequency questionnaire that included 121 food items
      was used to collect dietary information. Odds ratio (OR) and 95% confidence
      intervals (CI) were calculated using unconditional logistic regression analysis.
      RESULTS: For food groups, controls in the study consumed more vegetables, soy
      food and total fibre than did colorectal cancer patients (p<0.05). The intakes of
      fruit, meat and sea-food did not differ significantly between cases and controls.
      However, we did not find any association between soy food intake and colon
      cancer. We observed inverse associations between total fibre intake and
      colorectal, colon and rectal cancer (Q4 vs Q1: OR=0.44, 95%CI, 0.27- 0.73;
      OR=0.40, 95%CI, 0.21-0.76; OR=0.52, 95%CI, 0.29-0.91). Vegetable fibre intake
      showed similar inverse associations (Q4 vs Q1: OR=0.51, 95%CI, 0.31-0.85;
      OR=0.48, 95%CI, 0.25-0.91; OR=0.53, 95%CI, 0.29-0.97). In addition, inverse
      associations were observed between soluble fibre and insoluble fibre and both
      colorectal cancer and colon cancer. No relationship was found between colorectal
      cancer and fruit, soy or grain fibre intakewhen the results were stratified by
      tumour site. CONCLUSIONS: The present study suggests that vegetable fibre and
      total fibre play very important roles in protecting against colorectal cancer.
      Soluble and insoluble fibres were inversely associated with only colorectal
      cancer and colon cancer.

PMID- 25987033
TI  - Preparation and Evaluation of Chrysin Encapsulated in PLGA- PEG Nanoparticles in
      the T47-D Breast Cancer Cell Line.
AB  - BACKGROUND: Polymeric nanoparticles are attractive materials that have been
      widely used in medicine for drug delivery, with therapeutic applications. In our
      study, polymeric nanoparticles and the anticancer drug, chrysin, were
      encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol)
      (PLGA-PEG) nanoparticles for local treatment. MATERIALS AND METHODS: PLGA: PEG
      triblock copolymers were synthesized by ring-opening polymerization of D, L
      lactide and glycolide as an initiator. The bulk properties of these copolymers
      were characterized using 1H nuclear magnetic resonance spectroscopy and Fourier
      transform infrared spectroscopy. In addition, the resulting particles were
      characterized by scanning electron microscopy. RESULTS: The chrysin encapsulation
      efficiency achieved for polymeric nanoparticles was 70% control of release
      kinetics. The cytotoxicity of different concentration of pure chrysin and chrysin
      loaded in PLGA-PEG (5-640MUM) on T47-D breast cancer cell line was analyzed by
      MTT-assay. CONCLUSIONS: There is potential for use of these nanoparticles for
      biomedical applications. Future work should include in vivo investigation of the
      targeting capability and effectiveness of these nanoparticles in the treatment of
      breast cancer.

PMID- 25987034
TI  - Identification of High Affinity Non-Peptidic Small Molecule Inhibitors of MDM2
      p53 Interactions through Structure-Based Virtual Screening Strategies.
AB  - BACKGROUND: Approaches in disruption of MDM2-p53 interactions have now emerged as
      an important therapeutic strategy in resurrecting wild type p53 functional
      status. The present study highlights virtual screening strategies in
      identification of high affinity small molecule non-peptidic inhibitors. Nutlin3A
      and RG7112 belonging to compound class of Cis-imidazoline, MI219 of Spiro
      oxindole class and Benzodiazepine derived TDP 665759 served as query small
      molecules for similarity search with a threshold of 95%. The query molecules and
      the similar molecules corresponding to each query were docked at the
      transactivation binding cleft of MDM2 protein. Aided by MolDock algorithm, high
      affinity compound against MDM2 was retrieved. Patch Dock supervised Protein
      Protein interactions were established between MDM2 and ligand (query and similar)
      bound and free states of p53. Compounds with PubCid 68870345, 77819398, 71132874,
      and 11952782 respectively structurally similar to Nutlin3A, RG7112, Mi219 and TDP
      665759 demonstrated higher affinity to MDM2 in comparison to their parent
      compounds. Evident from the protein-protein interaction studies, all the similar
      compounds except for 77819398 (similar to RG 7112) showed appreciable inhibitory
      potential. Of particular relevance, compound 68870345 akin to Nutlin 3A had
      highest inhibitory potential that respectively showed 1.3, 1.2, 1.16 and 1.26
      folds higher inhibitory potential than Nutilin 3A, MI 219, RG 7112 and TDP
      1665759. Compound 68870345 was further mapped for structure based pharamacophoric
      features. In the study, we report Cis-imidazoline derivative compound; Pubcid:
      68870345 to have highest inhibitory potential in blocking MDM2-p53 interactions
      hitherto discovered.

PMID- 25987035
TI  - Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using
      Immunohistochemical Screening.
AB  - BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal,
      endometrial (uterine) and other cancers. Although most cancers are not inherited,
      about 5 percent (%) of people who have colorectal or endometrial cancer have the
      Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1,
      MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in
      colorectal cancer in a Malay cohort by immunohistochemistry. MATERIALS AND
      METHODS: A total of 17 patients were selected fulfilling one of the Bethesda
      criteria: colorectal cancer diagnosed in a patient aged less than 50 years old,
      having synchronous and metachronous colorectal cancer or with a strong family
      history. Immunohistochemical staining was performed on paraffin embedded tumour
      tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. RESULTS: Twelve
      out of 17 patients (70.6%) were noted to have a family history. A total of 41%
      (n=7) of the patients had abnormal immunohistochemical staining with one or more
      of the four antibodies. Loss of expression were noted in 13 tumour tissues with a
      negative staining score <4. Of 13 tumour tissues, four showed loss expression of
      MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6
      showed loss of expression in two tumour tissues respectively. CONCLUSIONS:
      Revised Bethesda criteria and immunohistochemical analysis constituted a
      convenient approach and is recommended to be a first-line screening for Lynch
      syndrome in Malay cohorts.

PMID- 25987037
TI  - Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer mcf-7
      cells.
AB  - Dietary prevention has been known to reduce breast cancer risk. Sesamin is one of
      the major components in sesame seeds and has been widely studied and proven to
      have anti-proliferation and anti-angiogenic effects on cancer cells. In this
      study, the influence of sesamin was tested in the human breast cancer MCF-7 cell
      line for cell viability (MTT assay) and cell cycling (flow cytometry). Results
      showed that sesamin dose-dependently (1, 10 and 50 MUM) reduced the cell
      viability and increased LDH release and apoptosis (TUNEL assay). In addition,
      there was a significant increase of sub-G1 phase arrest in the cell cycle after
      sesamin treatment. Furthermore, sesamin increased the expression of apoptotic
      markers of Bax, caspase-3, and cell cycle control proteins, p53 and checkpoint
      kinase 2. Taken together, these results suggested that sesamin might be used as a
      dietary supplement for prevention of breast cancer by modulating apoptotic signal
      pathways and inhibiting tumor cell growth. 

PMID- 25987036
TI  - Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete
      Resection.
AB  - BACKGROUND: This study aimed to establish a nomogram by combining
      clinicopathologic factors with overall survival of stage IA-IIB cervical cancer
      patients after complete resection with pelvic lymphadenectomy. MATERIALS AND
      METHODS: This nomogram was based on a retrospective study on 1,563 stage IA-IIB
      cervical cancer patients who underwent complete resection and lymphadenectomy
      from 2002 to 2008. The nomogram was constructed based on multivariate analysis
      using Cox proportional hazard regression. The accuracy and discriminative ability
      of the nomogram were measured by concordance index (C-index) and calibration
      curve. RESULTS: Multivariate analysis identified lymph node metastasis (LNM),
      lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion,
      tumor diameter and histology as independent prognostic factors associated with
      cervical cancer survival. These factors were selected for construction of the
      nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and
      calibration of the nomogram showed good agreement between the 5-year predicted
      survival and the actual observation. CONCLUSIONS: We developed a nomogram
      predicting 5-year overall survival of surgically treated stage IA-IIB cervical
      cancer patients. More comprehensive information that is provided by this nomogram
      could provide further insight into personalized therapy selection.

PMID- 25987038
TI  - Characterization of CEBPA Mutations and Polymorphisms and their Prognostic
      Relevance in De Novo Acute Myeloid Leukemia Patients.
AB  - The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that
      plays a crucial role in the control of proliferation and differentiation of
      myeloid precursors. This gene was recognized as the target of genetic alterations
      and were associated with clinical complexity among AML. We here analyze the
      frequency and types of CEBPA mutations and polymorphisms in a de novo AML
      patients from South India and tried to find out associations of these variations
      with different clinical parameters and the prognostic significance in AML. Study
      was carried out in 248 de novo AML patients, cytogenetic analysis was performed
      from the bone marrow samples and was karyotyped. PCR-SSCP analysis and sequencing
      was performed for the detection of CEBPA gene variations. All the statistical
      analysis was performed using SPSS 17 (statistical package for social sciences)
      software. Pearson Chi-square test, Mann-Whitney U test, Kaplan-Meier survival
      analysis and log rank tests were performed. CEBPA mutations were detected in 18%
      and CEBPA polymorphisms were detected in 18.9% of AML cases studied. Most of the
      mutations occured at the C terminal region. Polymorphisms were detected in both N
      and C terminal region. with most common being, c.584_589dup ACCCGC and c.690G>T.
      A significant association was not observed for the mutation and polymorphism with
      respect to clinical and laboratory parameters. Survival advantage was observed
      for the mutated cases compared to non mutated cases, especially for the normal
      karyotype groups. Polymorphisms has no effect on the survival pattern of AML
      patients. CEBPA mutation and polymorphisms were observed with similar frequency
      and was identified in all the FAB subtypes as well as in cytogenetic risk groups
      in our study population, but CEBPA mutations alone confer a prognostic value for
      NK AML patients. 

PMID- 25987039
TI  - Detection of BCR/ABL Fusion Gene by Hematological and Cytogenetical Analysis in
      Chronic Myeloid Leukemia Patients in Quetta, Pakistan.
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of
      pluripotent stem cells, caused by reciprocal translocation between the long arms
      of chromosomes 9 and 22, t(9;22)(q34;q11), known as the Philadelphia chromosome.
      MATERIALS AND METHODS: A total of 51 CML patients were recruited in this study.
      Complete blood counts of all CML patients were performed to find out their total
      leukocytes, hemoglobin and platelets. FISH was performed for the detection of BCR
      ABL fusion and cryptogenic tests using bone marrow samples were performed for the
      conformation of Ph (9;22)(q34;q11) and variant translocation mechanisms. RESULTS:
      In cytogenetic analysis we observed that out of 51 CML patients 40 (88.9%) were
      Ph positive and 4 (8.88%) had Ph negative chromosomes. Mean values of WBC 134.5
      103/MUl, hemoglobin 10.44 mg/dl, and platelets 288.6 103/MUl were observed in
      this study. CONCLUSIONS: In this study, Ph positive translocation between
      chromosome (9:22)(q34;q11) were observed in 40 (88.9%) CML patients.

PMID- 25987040
TI  - Persian Version of Functional Assessment of Cancer Therapy- Breast (FACT-B)
      Scale: Confirmatory Factor Analysis and Psychometric Properties.
AB  - BACKGROUND: The Functional Assessment of Cancer Therapy - Breast (FACT-B) scale
      is widely used to measure health-related quality of life in cancer patients. The
      aim of the present study is to validate the FACT-B in a sample of Iranian women
      with breast cancer. MATERIALS AND METHODS: The sample consisted of 300 women
      selected through non-random convenient sampling procedure from oncology hospitals
      and clinics in Kermanshah and Shiraz cities. They were asked to fill in the
      Persian versions of the FACT-B scale, Hospital Anxiety and Depression Scale, the
      European Organization for Research and Treatment of Cancer quality of life EORTC
      QLQ30. Confirmatory factorial analysis of the methods, concurrent validity and
      discriminant, and Cronbach's alpha for internal consistency were applied.
      RESULTS: Internal consistency using Cronbach's alpha was 0.63 to 0.93 for the
      subscales and 0.92 for the total scale. Significant correlations between FACT- B
      and other measures indicate that this scale had concurrent and discriminant
      validity. The values of fit indices were satisfactory. CONCLUSIONS: The Persian
      version of the FACT-B scale is valid and reliable and, therefore, the scale can
      be used in research and clinical settings to assess health-related quality of
      life in Iranian patients with breast cancer.

PMID- 25987041
TI  - Arsenic Trioxide Inhibits Cell Growth and Invasion via Down- Regulation of Skp2
      in Pancreatic Cancer Cells.
AB  - Arsenic trioxide (ATO) has been found to exert anti-cancer activity in various
      human malignancies. However, the molecular mechanisms by which ATO inhibits
      tumorigenesis are not fully elucidated. In the current study, we explored the
      molecular basis of ATO-mediated tumor growth inhibition in pancreatic cancer
      cells. We used multiple approaches such as MTT assay, wound healing assay,
      Transwell invasion assay, annexin V-FITC, cell cycle analysis, RT-PCR and Western
      blotting to achieve our goal. We found that ATO treatment effectively caused cell
      growth inhibition, suppressed clonogenic potential and induced G2-M cell cycle
      arrest and apoptosis in pancreatic cancer cells. Moreover, we observed a
      significant down-regulation of Skp2 after treatment with ATO. Furthermore, we
      revealed that ATO regulated Skp2 downstream genes such as FOXO1 and p53. These
      findings demonstrate that inhibition of Skp2 could be a novel strategy for the
      treatment of pancreatic cancer by ATO. 

PMID- 25987043
TI  - Novel DOT1L ReceptorNatural Inhibitors Involved in Mixed Lineage Leukemia: a
      Virtual Screening, Molecular Docking and Dynamics Simulation Study.
AB  - BACKGROUND: The human protein methyl-transferase DOT1L catalyzes the methylation
      of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a
      number of significant processes ranging from gene expression to DNA-damage
      response and cell cycle progression. Inhibition of DOT1L activity by shRNA or
      small-molecule inhibitors has been established to prevent proliferation of
      various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive
      therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently
      in use for the MLL treatment are reported to have low efficacy, hence this study
      focused on various natural compounds which exhibit minimal toxic effects and high
      efficacy for the target receptor. MATERIALS AND METHODS: Structures of human
      protein methyl-transferase DOT1L and natural compound databases were downloaded
      from various sources. Virtual screening, molecular docking, dynamics simulation
      and drug likeness studies were performed for those natural compounds to evaluate
      and analyze their anti-cancer activity. RESULTS: The top five screened compounds
      possessing good binding affinity were identified as potential high affinity
      inhibitors against DOT1L's active site. The top ranking molecule amongst the
      screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score
      of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's
      behaviour also showed consistency during the simulation of protein-ligand complex
      for 20000 ps, which is indicative of its stability in the receptor pocket.
      CONCLUSIONS: The ligand obtained out of this screening study can be considered as
      a potential inhibitor for DOT1L and further can be treated as a lead for the drug
      designing pipeline.

PMID- 25987042
TI  - Prognostic significance of Hes-1, a downstream target of notch signaling in
      hepatocellular carcinoma.
AB  - BACKGROUND: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target
      of Notch signaling and is a basic helix-loop-helix transcriptional repressor.
      However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells
      has not been reported. Here, Hes-1 was revealed to an important component of the
      Notch signaling cascade in HCC cell lines possessing different potential for lung
      metastasis. MATERIALS AND METHODS: RNAi mediated by plasmid constructs was used
      to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation,
      apoptosis, cell migration and matrigel invasion following transfection. Hes-1
      protein expression analysis in HCC tissue was also conducted by
      immunohistochemistry. RESULTS: Our studies revealed that Hes-1 was decreased in
      HCC cell lines with higher lung metastasis potential at both the mRNA and protein
      levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased
      cell proliferation, reduced apoptosis and increased migration and invasion.
      CONCLUSIONS: Hes-1 has potential prognostic value in post-surgical HCC patients
      and may be an independent prognostic indicator for overall survival and tumor
      recurrence. These findings have important implications for understanding the
      mechanisms by which Hes-1 participates in tumor proliferation and invasion.

PMID- 25987044
TI  - Extended field radiotherapy with or without chemotherapy in patients with
      cervical cancer and positive para-aortic lymph nodes: a single institution
      retrospective review.
AB  - BACKGROUND: Positive para-aortic lymph node (PALN) at diagnosis in cervical
      cancer patients confers an unfavorable prognosis. This study reviewed the
      outcomes of extended field radiotherapy (EFRT) and concurrent chemotherapy with
      extended field RT (CCEFRT) in patients with positive PALN at diagnosis. MATERIALS
      AND METHODS: Medical records of 407 cervical cancer patients between 1st January
      2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were
      identified to have received definitive extended field radiotherapy with or
      without chemotherapy. Treatment outcomes, clinicopathological factors affecting
      survival and radiotherapy related acute and late effects were analyzed. RESULTS:
      Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the
      period of review. The median follow-up was 70 months. The 5-year overall survival
      (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients
      who had EFRT alone, with median survival sof 29 months and 13 months,
      respectively. The 5-years progression free survival (PFS) for patients who
      underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18
      months and 12 months, respectively. Overall treatment time (OTT) less than 8
      weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented
      in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four
      patients (12.5%) developed radiotherapy late toxicity and there was no treatment
      related death observed. CONCLUSIONS: CCEFRT is associated with higher 5-years OS
      and median OS compared to EFRT and with tolerable level of acute and late
      toxicities in selected patients with cervical cancer and PALN metastasis.

PMID- 25987045
TI  - IOTA Simple Rules in Differentiating between Benign and Malignant Adnexal Masses
      by Non-expert Examiners.
AB  - OBJECTIVE: To evaluate the diagnostic performance of IOTA simple rules in
      predicting malignant adnexal tumors by non-expert examiners. MATERIALS AND
      METHODS: Five obstetric/gynecologic residents, who had never performed
      gynecologic ultrasound examination by themselves before, were trained for IOTA
      simple rules by an experienced examiner. One trained resident performed
      ultrasound examinations including IOTA simple rules on 100 women, who were
      scheduled for surgery due to ovarian masses, within 24 hours of surgery. The gold
      standard diagnosis was based on pathological or operative findings. The five
      trained residents performed IOTA simple rules on 30 patients for evaluation of
      inter-observer variability. RESULTS: A total of 100 patients underwent ultrasound
      examination for the IOTA simple rules. Of them, IOTA simple rules could be
      applied in 94 (94%) masses including 71 (71.0%) benign masses and 29 (29.0%)
      malignant masses. The diagnostic performance of IOTA simple rules showed
      sensitivity of 89.3% (95%CI, 77.8%; 100.7%), specificity 83.3% (95%CI, 74.3%;
      92.3%). Inter-observer variability was analyzed using Cohen's kappa coefficient.
      Kappa indices of the four pairs of raters are 0.713-0.884 (0.722, 0.827, 0.713,
      and 0.884). CONCLUSIONS: IOTA simple rules have high diagnostic performance in
      discriminating adnexal masses even when are applied by non-expert sonographers,
      though a training course may be required. Nevertheless, they should be further
      tested by a greater number of general practitioners before widely use.

PMID- 25987046
TI  - Pemetrexed in treating patients with metastatic bladder cancer.
AB  - BACKGROUND: This pooled analysis was conducted to evaluate the efficacy and
      safety of pemetrexed based chemotherapy in treating patients with metastatic
      bladder cancer as salvage chemotherapy. METHODS: Clinical studies evaluating the
      efficacy and safety of pemetrexed based regimens on response and safety for
      patients with bladder cancer were identified by using a predefined search
      strategy. Pooled response rate (RR) of treatment were calculated. RESULTS: In
      pemetrexed based regimens, 3 clinical studies which including 105 patients with
      advanced transitional cell cancer of the urothelium were considered eligible for
      inclusion. Pooled analysis suggested that, in all patients, pooled RR was 26.7%
      (28/105) for pemetrexed based regimens. Major adverse effects were neutropenia,
      anorexia, fatigue, and anemia in pemetrexed based treatment. Two treatment
      related deaths occurred with pemetrexed based treatment. CONCLUSION: This pooled
      analysis suggests that pemetrexed based regimens are associated with mild
      activity and good tolerability in treating patients with metastatic bladder
      cancer.

PMID- 25987047
TI  - Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16
      E6 and E7 Fusion Gene in Vivo and in Vitro.
AB  - BACKGROUND: Cervical cancer is the second most common cause of cancer related
      death of women. Persistent HPV infection, especially with high-risk types such as
      HPV16 and HPV18, has been identified to be the primary cause of cervical cancer.
      E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed
      exclusively in HPV infected tissues, and thereby represent ideal therapeutic
      targets for immunotherapy of cervical cancer. MATERIALS AND METHODS: In this
      work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7
      fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate
      the ability of primed DC vaccine in eliciting antitumor immunity in vitro and
      vivo. RESULTS: Our results indicated that DC-ofE6E7 vaccine co-culturing with
      splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL)
      response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7
      vaccine induced protective immunity against the challenge of TC-1 cancer cells in
      vivo. CONCLUSIONS: The results suggested that the HPV16 ofE6E7 primed DC vaccine
      has potential application for cervical cancer immunotherapy.

PMID- 25987048
TI  - ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-alpha Stimulated Invasive
      Cholangiocarcinoma Cells.
AB  - BACKGROUND: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a
      high mortality rate due to a lack of effective early diagnosis and treatment.
      Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer
      progression would contribute toward the development of novel tumor markers and
      effective chemotherapy. MATERIALS AND METHODS: An invasive CCA cell line (KKU
      100) was stimulated using TNF-alpha and then biotinylated and purified for mass
      spectrometry analysis. Novel proteins expressed were selected and their mRNAs
      expression levels were determined by real-time RT-PCR. In addition, the
      expression of ALCAM was selected for further observation by Western blot
      analysis, immunofluorescent imaging, and antibody neutralization assay. RESULTS:
      After comparing the proteomics profile of TNF-alpha induced invasive with non
      treated control cells, over-expression of seven novel proteins was observed in
      the cytoplasmic membrane of TNF-alpha stimulated CCA cells. Among these, ALCAM is
      a novel candidate which showed significant higher mRNA- and protein levels.
      Immunofluorescent assay also supported that ALCAM was expressed on the cell
      membrane of the cancer, with increasing intensity associated with TNF-alpha.
      CONCLUSIONS: This study indicated that ALCAM may be a novel protein candidate
      expressed on cytoplasmic membranes of invasive CCA cells that could be used as a
      biomarker for development of diagnosis, prognosis, and drug or antibody-based
      targeted therapies in the future.

PMID- 25987049
TI  - Correlation between Serum Carcinoembryonic Antigen Level and Histologic Subtype
      in Resected Lung Adenocarcinoma.
AB  - BACKGROUND: Recent studies revealed a relationship between ground-glass opacity
      (GGO) ratio on computed tomography (CT) and serum carcinoembryonic antigen (CEA)
      level in lung adenocarcinoma. Since an association between lepidic histologic
      pattern and GGO is well accepted, we investigated the link between histologic
      subtype and serum CEA level in resected lung adenocarcinoma. MATERIALS AND
      METHODS: One hundred and eighty-one consecutive patients with resected lung
      adenocarcinoma were studied retrospectively. The histologic subtype was
      subdivided into 2 groups: lepidic dominant histologic subtype, including
      adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant
      invasive adenocarcinoma versus other subtypes. RESULTS: The 5-year survival of
      patients with s high serum CEA level was significantly more unfavorable than that
      with normal levels. Similarly, there was also a relationship between the patient
      survival and histologic subtype, with favorable survival found in patients with
      the lepidic dominant histologic subtype. There was a significant relationship
      between serum CEA level and lepidic dominant histologic subtype overall and in p
      stage I patients. CONCLUSIONS: Lung adenocarcinomas with non-lepidic dominant
      histologic subtype are associated with high serum CEA levels.

PMID- 25987050
TI  - Relapse patterns and outcomes following recurrence of endometrial cancer in
      northern Thai women.
AB  - BACKGROUND: The aim of this study was to analyze the patterns of relapse and
      survival outcomes in Northern Thai women with recurrent endometrial cancer (EC).
      MATERIALS AND METHODS: Medical records were abstracted from EC patients who
      underwent primary surgery from 1999 to 2012. Data on clinicopathologic variables,
      sites of first recurrence, time to relapse of disease, and overall survival (OS)
      was analyzed. Associations between the clinicopathological variables and the
      rates of disease recurrence were determined. RESULTS: Among 1,204 reviewed
      records, 42 eligible patients were identified with recurrent disease. The median
      age was 55 years and the median follow-up time was 26.0 months. The median times
      to recurrence (TTR) after completion of the initial treatment in the group of
      local relapse (LR) and distant/combined sites of recurrence (DCSR) was 6.6 (95%
      CI=4.6 to 8.6 months) and 16.9 months (95% CI=5.6 to 28.2 months), respectively
      (p=0.36). The 2-year survival and 3-year survival probability in the group of LR
      was 54.2% (95% CI=27.2 to 81.3%) and 34.7% (95% CI=9.2 to 60.2%), compared to
      50.4% (95% CI=41.1 to 59.7%) and 42.1% (95%CI= 24.1 to 60.1%) for those with
      DCSR. Distant recurrence was the most frequent pattern of relapse. Overall
      survival was not significantly different in patients with local relapse when
      compared to those with DCSR (p=0.69). CONCLUSIONS: Patients with recurrence of EC
      after primary treatment had a worse prognosis and clinical aggressiveness. LR and
      DCSR occurred most during the first three years. The common sites of relapses
      were vaginal cuff, pelvis, and lungs. No significant clinicopathological
      predictor for survival outcomes was identified.

PMID- 25987051
TI  - Value of Combined Detection of Serum CEA, CA72-4, CA19-9 and TSGF in the
      Diagnosis of Gastric Cancer.
AB  - BACKGROUND: To explore whether combined detection of serum tumor markers (CEA,
      CA72-4, CA19-9 and TSGF) improve the sensitivity and accuracy in the diagnosis of
      gastric cancer (GC). MATERIALS AND METHODS: An automatic chemiluminescence immune
      analyzer with matched kits were used to determine the levels of serum CEA, CA72
      4, CA19-9 and TSGF in 45 patients with gastric cancer (GC group), 40 patients
      with gastric benign diseases (GBD group) hospitalized in the same period and 30
      healthy people undergoing a physical examination. The values of those 4 tumor
      markers in the diagnosis of gastric cancer was analyzed. RESULTS: The levels of
      serum CEA, CA72-4, CA19-9 and TSGF of the GC group were higher than those of the
      GBD group and healthy examined people and the differences were significant
      (P<0.001). The area under receiver operating characteristic (ROC) curves for
      single detection of CEA, CA72-4, CA19-9 and TSGF in the diagnosis of GC was
      0.833, 0.805, 0.810 and 0.839, respectively. The optimal cutoff values for these
      4 indices were 2.36 ng/mL, 3.06 U/mL, 5.72 U/ mL and 60.7 U/mL, respectively.
      With combined detection of tumor markers, the diagnostic power of those 4 indices
      was best, with an area under the ROC curve of 0.913 (95%CI 0.866~0.985), a
      sensitivity of 88.9% and a diagnostic accuracy of 90.4%. CONCLUSIONS: Combined
      detection of serum CEA, CA72-4, CA19-9 and TSGF increases the sensitivity and
      accuracy in diagnosis of GC, so it can be regarded as the important means for
      early diagnosis.

PMID- 25987052
TI  - Association of the miRNA146a rs2910164 C>G Polymorphism with Head and Neck Cancer
      Risk: A Meta-analysis.
AB  - OBJECTIVE: To investigate any association of the miRNA146a rs2910164 C>G
      polymorphism with head and neck cancer risk. MATERIALS AND METHODS: The Medline,
      PubMed, PUBMED, EMBASE, Web of Science, WanFang and CNKI databases were searched
      and a meta-analysis was conducted using RevMan 5.2 software. RESULTS: After
      searching and evaluating the literature, a total seven papers involving 2,766
      patients with head and neck cancer and 6,603 healthy controls were included into
      this meta analysis. The results showed that there were no significant differences
      between patients and healthy controls overall for the miRNA rs2910164 C>G gene
      polymorphism (dominant model:OR=0.78, 95%CI:0.58-1.04, P=0.09; recessive
      model:OR=0.86, 95%CI:0.67-1.12, P=0.27;GG:CC:OR=0.75, 95%CI:0.52-1.08,
      P=0.12;GC:CC:OR=0.79, 95%CI:0.60-1.04, P=0.10). However, a significant
      association of miRNA rs2910164 C>G gene polymorphism with Chinese head and neck
      cancer risk was noted, limited to the dominant model (OR=0.68, 95%CI:0.50-0.95,
      P=0.02;GG:CC:OR=0.62, 95%CI:0.42-0.92, P=0.02;GC:CC:OR=0.72, 95%CI:0.520.99,
      P=0.04). CONCLUSIONS: miRNA146a rs2910164 C>G polymorphism is not associated with
      head and neck cancer risk in general, but tehre may be link in Chinese.

PMID- 25987053
TI  - May the neutrophil/lymphocyte ratio be a predictor in the differentiation of
      different thyroid disorders?
AB  - BACKGROUND: The neutrophil/lymphocyte ratio (NLR) is a simple index of systemic
      inflammatory response, and has been shown to be a prognostic indicator in some
      types of cancer. Inflammation has been implicated in the initiation and
      progression of thyroid cancer. The aim of this study was to examine the
      relationship of NLR with papillary thyroid cancer (PTC) and different benign
      thyroid pathologies like multinodular goiter (MNG) and lymphocytic thyroiditis
      (LT). MATERIALS AND METHODS: We retrospectively evaluated the neutrophil,
      lymphocyte counts and NLR calculated from these parameters of 232 patients with
      histologically confirmed as multinodular goiter (group MNG) (n=70), lymphocytic
      thyroiditis (group LT) (n=97), LT with PTC (group LT- PTC) (n=25) and PTC (group
      PTC) (n=40). The optimal cut-off value for NLR was determined. RESULTS: NLR level
      was significantly higher in groups LT-PTC and PTC as compared to groups MNG and
      LT (p<0.05). NLR of LT subgroups according to TSH levels were not different
      (p>0.05). When we grouped the patients as benign and malignant according to PTC
      presence, the optimum NLR cut-off point obtained from ROC analysis was 1.91
      (sensitivity 89.0% and specificity 54.5%). CONCLUSIONS: Since NLR was
      significantly elevated in group LT-PTC and group PTC, NLR value may give an
      opinion as a potential marker in differentiation of benign and malign thyroid
      disorders. For this purpose a cut-off value of 1.91 for NLR may be accepted.

PMID- 25987054
TI  - Inhibition of Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a
      High-fat Diet by Pleurotus eryngii (Eringi) and Hypsizygus marmoreus
      (Bunashimeji).
AB  - Obesity markedly increases the risk of colorectal cancer. Recently, the
      preventive effects of edible mushrooms on triglyceride elevation and visceral fat
      accumulation have been reported. Here, the effects of Pleurotus eryngii (Eringi)
      and Hypsizygus marmoreus (Bunashimeji) on azoxymethane (AOM)-induced aberrant
      crypt foci (ACF; precancerous lesions) in the colorectums of mice fed a high-fat
      diet were examined. Eringi (ER) and Bunashimeji (BU) mushroom powder samples were
      used. Six-week-old male C57BL/6J mice received an intraperitoneal injection of
      AOM (10 mg/kg) once a week for two weeks, and were sacrificed and dissected at 6
      weeks after the start of the experiment. After the initiation of the experiment,
      they received a normal diet (ND), high-fat diet (HFD), HFD + ER (1 or 5% of
      diet), or HFD + BU (1 or 5% of diet). As a result, body and fat weights were
      significantly lower in the 5% ER and BU groups than in the HFD group. Liver
      triglyceride levels were also significantly lower in the 5% ER and BU groups.
      Total liver cholesterol levels were significantly lower in the 5% ER group. The
      numbers of ACF (especially large ACF) showed strong inhibitory effects in both ER
      and BU groups. Measurement of the cell proliferation marker Ki-67 labeling index
      in the colonic mucosa demonstrated more significant suppression in both ER and BU
      groups than in the HFD group. These results suggest that the simultaneous intake
      of ER and BU may inhibit colorectal tumorigenesis in HFD-fed mice. 

PMID- 25987055
TI  - Effects of Aloe-emodin and Emodin on Proliferation of the MKN45 Human Gastric
      Cancer Cell Line.
AB  - Aloe-emodin (1, 8-dihydroxy-3-hydroxyl-methylanthraquinone; AE) and emodin (1,3,8
      trihydroxy-6- methylanthraquinone; EM) are anthraquinone derivatives that have
      been detected in some medical plants and share similar anthraquinone structures.
      AE and EM have been shown to exhibit anticancer activities in various cancer cell
      lines; however, the inhibitory effects of these derivatives on the growth of
      cancer cells were previously reported to be different. Gastric cancer is the
      second most common cause of cancer cell death worldwide. In the present study, we
      examined the inhibitory effects of 0.05 mM AE and 0.05 mM EM on the proliferation
      of the MKN45 human gastric cancer cell line. The proliferation of MKN45 cells was
      significantly inhibited in AE- and EM-treated groups 24 h and 48 h after
      treatment. Furthermore, the inhibitory effects of EM were stronger than those of
      AE. The cell cycle of MKN45 cells were arrested in G0/G1 phase or G0/G1 and G2/M
      phases by AE and EM, respectively. However, an analysis of intracellular
      polyamine levels and DNA fragmentation revealed that the mechanisms underlying
      cell death following cell arrest induced by AE and EM differed. 

PMID- 25987056
TI  - Multiple Sexual Partners as a Potential Independent Risk Factor for Cervical
      Cancer: a Meta-analysis of Epidemiological Studies.
AB  - It's known that having multiple sexual partners is one of the risk factors of
      human papillomavirus (HPV) infection which is a major cause of cervical cancer.
      However, it is not clear whether the number of sexual partners is an independent
      risk factor for cervical cancer. We identified relevant studies by searching the
      databases of MEDLINE, PubMed and ScienceDirect published in English from January
      1980 to January 2014. We analyzed those studies by combining the study-specific
      odds ratios (ORs) using random-effects models. Forty-one studies were included in
      this meta-analysis. We observed that the number of sexual partners was associated
      with the occurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00)
      and invasive cervical carcinoma (OR=1.77, 95%CI 1.50-2.05). Subgroup analyses
      revealed that the association remained significant after controlling for HPV
      infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI
      1.30- 1.76 for invasive cervical carcinoma). We found that there was a non-linear
      relation of the number of sexual partners with both non-malignant cervical
      disease and invasive cervical carcinoma. The risk of both malignant and non
      malignant disease is relatively stable in women with more than 4-7 sexual
      partners. Furthermore, the frequency-risk of disease remained significant after
      controlling for HPV infection.The study suggested that having multiple sexual
      partners, with or without HPV infection, is a potential risk factor of cervical
      cancer. 

PMID- 25987057
TI  - Regulation Roles of MICA and NKG2D in Human Renal Cancer Cells.
AB  - OBJECTIVE: Our aim was to investigation the roles of MHC class I chain-related
      gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells.
      MATERIALS AND METHODS: The expression of membrane MICA (mMICA) on renal cells and
      NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA
      were detected by enzyme linked immunosorbent assay (ELISA) and the distribution
      of mMICA on renal tumor tissues by immunohistochemistry; the interaction between
      MICA and NKG2D was observed by antibody closed method. RESULTS: Our results
      showed that the expression of mMICA in renal cancer tissues was significantly
      higher than in controls, where the soluble MICA was not expressed. Cytotoxic
      activity of NK cells was significantly reduced after exposure to NKG2D and MICA
      antibodies (P<0.05), and serum containing sMICA can obviously lower the function
      of NKG2D (P<0.05). CONCLUSIONS: The interaction of mMICA and NKG2D play important
      roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA
      may mediate tumor immune escape through down- regulated NKG2D expression.

PMID- 25987059
TI  - Efficacy of mannatide combined with sodium cantharidate vitamin B6 in the
      treatment of malignant pleural effusions.
AB  - OBJECTIVE: To evaluate the efficacy of mannatide combined with sodium
      cantharidate vitamin B6 in the treatment of malignant pleural effusions.
      MATERIALS AND METHODS: Data for 69 patients with malignant pleural effusions who
      did not receive systemic chemotherapy were collected. Injection into the thorax
      using mannatide combined with sodium cantharidate vitamin B6 was performed for 37
      patients in the experimental group and mannatide combined with cisplatin for 32
      patients in the control group. Objective responses, KPS (Karnofsky Scoring) and
      incidences of side effects between the two groups were compared. RESULTS: 13
      patients reached CR (complete response) and 11 PR (partial response) in the
      experimental group, while 12 patients reached CR and 9 PR in the control group,
      the difference in overall objective responses between the two groups not being
      significant (66.7% vs 63.6%, p=0.806). However, improvement of KPS in the
      experimental group was greater than in the control group; total side-effect
      incidences during the period of treatment were 22.2% (8/36) and 54.5% (18/33),
      respectively (p=0.006). CONCLUSIONS: Regimen of mannatide combined with sodium
      cantharidate vitamin B6 had better improvement in quality-of-life and symptom
      relief, with a lower side-effect incidence in treatment of malignant pleural
      effusions.

PMID- 25987058
TI  - Antitumor activity of chloroquine in combination with Cisplatin in human gastric
      cancer xenografts.
AB  - PURPOSE: To investigate the antitumor activity and mechanism of chloroquine (CQ)
      in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer
      SGC7901 cells. MATERIALS AND METHODS: 35 cases of gastric cancer patients with
      malignant ascites were enrolled and intraperitoneal cisplatin injection was
      performed. Ascites were collected before and 5 days after perfusion for
      assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing
      mice were randomly divided into control, DDP, CQ and CQ + DDP groups. RESULTS: In
      54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5
      days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin
      1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1
      (P=0.001). Compared with the control group, the xenograft growth in nude mice in
      the DDP group was low, and the inhibition rate was 47.6%. In combination with
      chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio,
      and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein
      levels increased (P<0.05). CONCLUSIONS: Antitumor ability of cisplatin was
      associated with autophagy activity and chloroquine can enhance chemosensitivity
      to cisplatin in gastric cancer xenografts nude mice.

PMID- 25987060
TI  - Dendrosomal curcumin suppresses metastatic breast cancer in mice by changing
      m1/m2 macrophage balance in the tumor microenvironment.
AB  - Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has
      been found to exert immunomodulatory effects via macrophages. However, most
      studies focus on the low bioavailability issue of curcumin by nano and
      microparticles, and thus the role of macrophages in the anticancer mechanism of
      curcumin has received little attention so far. We have previously shown the
      potential biocompatibility, biodegradability and anti-cancer effects of
      dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equally
      divided into control as well as 40 and 80 mg/kg groups of DNC to investigate the
      involvement of macrophages in the antitumor effects of curcumin in a typical
      animal model of metastatic breast cancer. At the end of intervention, the tumor
      volume and weight were significantly reduced in DNC groups compared to control
      (P<0.05). Histopathological data showed the presence of macrophages in tumor and
      spleen tissues. Real-time PCR results showed that DNC increased the expression of
      STAT4 and IL-12 genes in tumor and spleen tissues in comparison with control
      (P<0.05), referring to the high levels of M1 macrophages. Furthermore treatment
      with DNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05),
      indicating low levels of M2 macrophage. The results confirm the role of
      macrophages in the protective effects of dendrosomal curcumin against metastatic
      breast cancer in mice. 

PMID- 25987061
TI  - Estimation of survival rates in patients with lung cancer in west Azerbaijan, the
      northwest of Iran.
AB  - BACKGROUND: Lung cancer is a fatal malignancy with high mortality and short
      survival time. The aim of this study was to estimate survival rates of Iranian
      patients with lung cancer and its associate predictive factors. MATERIALS AND
      METHODS: The study was conducted on 355 patients admitted to hospitals of West
      Azerbaijan in the year 2007. The patients were followed up by phone calls until
      the end of June 2014. The survival rate was estimated using the Kaplan-Meier
      method and log-rank test for comparison. The Cox's proportional hazard model was
      used to investigate the effect of various variables on patient survival time,
      including age, sex, Eastern Cooperative Oncology Group (ECOG) performance,
      smoking status, tumor type, tumor stage, treatment, metastasis, and blood
      hemoglobin concentration. RESULTS: Of the 355 patients under study, 240 died and
      115 were censored. The mean and median survival time of patients was 13 and 4.8
      months, respectively. According to the results of Kaplan-Meier method, 1, 2, and
      3 years survival rates were 39%, 18%, and 0.07%, respectively. Based on Cox
      regression analysis, the risk of death was associated with ECOG group V (1.83,
      95% CI: 1 CONCLUSIONS: The survival time of the patients with lung cancer is very
      short. While early diagnosis may improve the life expectancy effective treatment
      is not available.

PMID- 25987062
TI  - Poor knowledge of colorectal cancer in Brunei Darussalam.
AB  - BACKGROUND: Colorectal cancer (CRC) is the most common gastrointestinal cancer
      and the incidence is increasing in many developing countries. While it can be
      detected early and even prevented through screening and removal of premalignant
      lesions, there are barriers to screening which include low level of knowledge and
      awareness of CRC. This study assessed the level of knowledge of CRC in Brunei
      Darussalam. MATERIALS AND METHODS: A total of 431 (262 male and 161 female)
      subjects participated in this questionnaire study. Subjects were scored on their
      knowledge of signs/symptoms (maximum 10 correct answers) and known risk factors
      for CRC (maximum 10 correct answers) and were categorised into poor (0-2),
      moderate (3-4) and satisfactory (5-10). Comparisons were made between the various
      patient factors. RESULTS: Overall, 54.1% could not name any CRC signs/symptoms or
      associated risk factors. Most were not aware of any screening modalities. The
      overall scores for CRC signs/symptoms and risk factors were 1.3+/-1.39 (range 0
      6) and 0.6+/-1.05 (range 0-5) respectively. Overall, the breakdown of scores was:
      poor (78.1%), moderate (20.3%) and satisfactory (6.2%) for signs/symptoms and
      poor (93.2%), moderate (6.2%) and satisfactory (0.7%) for risk factors. Higher
      level of education, female gender and non-Malay race were associated with higher
      scores for both signs/symptoms and knowledge of screening modality; however the
      overall scores were low. CONCLUSIONS: Our study showed that the general knowledge
      of CRC in Brunei Darussalam is poor. Being female, with higher levels of
      education and non-Malay race were associated with higher scores, but they were
      still generally poor. More needs to be done to increase the public knowledge and
      awareness of CRC.

PMID- 25987063
TI  - Association between Diabetes Mellitus and Fatty Liver Based on Ultrasonography
      Screening in the World's Highest Cholangiocarcinoma Incidence Region, Northeast
      Thailand.
AB  - Fatty liver disease (FLD) can be a precondition for other liver pathology
      including cholangiocarcinoma (CCA). Diabetes mellitus (DM) has been suggested in
      some studies to be a risk factor for FLD as well as cancers, including
      cholangiocellular carcinoma; however, there are currently very few studies on FLD
      in DM subjects, although the rate of FLD continues to increase annually. To
      determine the association between DM and FLD ultrasonographic data were analyzed
      from the Cholangiocarcinoma Screening and Care Program (CASCAP), in northeast
      Thailand. DM was reported by the subjects based on the CASCAP health
      questionnaire. Factors that were associated with FLD were determined by
      prevalence, odds ratio (ORs) and its 95% confidence intervals (CIs) using
      multiple logistic regression. There were 45,263 subjects with a mean age of 53.46
      (+/-9.25) years. FLD was found in 36.3% of DM subjects but only in 20.7% of non
      DM subjects. The association between DM and FLD was adjusted for all other
      factors including gender, age, education level, relatives diagnosed with CCA,
      smoking, alcohol consumption, and hepatitis B and C. The risk of DM in subjects
      having FLD was highly significant compared with the non-DM subjects (OR 2.13;
      95%CI: 1.92 to 2.35; p-value < 0.001). Thus DM is significantly associated with
      FLD which in turn may facilitate the development of several diseases including
      CCA. DM should be taken into consideration in future ultrasonic investigations of
      FLD and CCA. 

PMID- 25987064
TI  - Metformin may improve the prognosis of patients with pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer risk is increased in patients with type 2 diabetes,
      while being reduced by metformin treatment. However, it is unclear whether
      metformin could be associated with clinical outcomes of patients with pancreatic
      cancer and concurrent type 2 diabetes. MATERIALS AND METHODS: A pooled analysis
      of 4 publications including 1,429 patients was performed to investigate the
      association of metformin and overall survival(OS) in patients with pancreatic
      cancer and concurrent type 2 diabetes. RESULTS: A borderline significant relative
      survival benefit was found in metformin treated patients compared with non
      metformin treated patients (hazard ratio 0.80; 95% CI: 0.62-1.03). CONCLUSIONS:
      These results suggest that further investigation is warranted of whether
      metformin may benefit the survival of patients with pancreatic cancer and
      concurrent type 2 diabetes.

PMID- 25987065
TI  - Aberrant Expression of HOXA5 and HOXA9 in AML.
AB  - BACKGROUND: Aberrant expression of HOX gene expression has been observed in
      cancer. The purpose of this study was to investigate the alteration of HOXA5 and
      HOXA9 expression and their clinical significance in acute meloid leukemia (AML).
      MATERIALS AND METHODS: The expression of HOXA5 and HOXA9 genes of bone marrow
      samples from 75 newly diagnosed AML patients and 22 healthy controls for
      comparison were examined by Real- time quantitative PCR (RQ-PCR) assay.
      Statistical analysis was conducted to evaluate HOXA5 and HOXA9 expression as
      possible biomarkers for AML. RESULTS: The results showed that the complete
      remission rate (52.6%) of the patients who highly expressed HOXA5 and HOXA9 was
      significantly lower than that (88.9%) in patients who lowly express the genes
      (P=0.015). Spearmann correlation coefficients indicated that the expression
      levels for HOXA5 and HOXA9 genes were highly interrelated (r=0.657, P<0.001).
      Meanwhile, we detected significant correlations between HOXA9 expression and age
      in this limited set of patients (P=0.009). CONCLUSIONS: The results suggest a
      prognostic impact of increased expression of HOXA5 and HOXA9 in AML patients.

PMID- 25987066
TI  - Utrecht Interstitial Applicator Shifts and DVH Parameter Changes in 3D CT-based
      HDR Brachytherapy of Cervical Cancer.
AB  - BACKGROUND: For brachytherapy of cervical cancer, applicator shifts can not be
      avoided. The present investigation concerned Utrecht interstitial applicator
      shifts and their effects on organ movement and DVH parameters during 3D CT-based
      HDR brachytherapy of cervical cancer. MATERIALS AND METHODS: After the applicator
      being implanted, CT imaging was achieved for oncologist contouring CTVhr, CTVir,
      and OAR, including bladder, rectum, sigmoid colon and small intestines. After the
      treatment, CT imaging was repeated to determine applicator shifts and OARs
      movements. Two CT images were matched by pelvic structures. In both imaging
      results, we defined the tandem by the tip and the base as the marker point, and
      evaluated applicator shift, including X, Y and Z. Based on the repeated CT
      imaging, oncologist contoured the target volume and OARs again. We combined the
      treatment plan with the repeated CT imaging and evaluated the change range for
      the doses of CTVhr D90, D2cc of OARs. RESULTS: The average applicator shift was 
      0.16 mm to 0.10 mm for X, 1.49 mm to 2.14 mm for Y, and 1.9 mm to 2.3 mm for Z.
      The change of average physical doses and EQD2 values in Gyalpha/beta range for
      CTVhr D90 decreased by 2.55 % and 3.5 %, bladder D2cc decreased by 5.94 % and
      8.77 %, rectum D2cc decreased by 2.94 % and 4 %, sigmoid colon D2cc decreased by
      3.38 % and 3.72 %, and small intestines D2cc increased by 3.72 % and 10.94 %.
      CONCLUSIONS: Applicator shifts and DVH parameter changes induced the total dose
      inaccurately and could not be ignored. The doses of target volume and OARs varied
      inevitably.

PMID- 25987067
TI  - Recent Decrease in Colorectal Cancer Mortality Rate is Affected by Birth Cohort
      in Korea.
AB  - BACKGROUND: Colorectal cancer mortality has started to decrease in several
      developed countries in Asia. The current study aimed to present the long-term
      trends in colorectal cancer mortality in Korea using joinpoint analysis and age
      period-cohort modeling. MATERIALS AND METHODS: The number of colorectal cancer
      deaths and the population for each 5-year age group were obtained from Statistics
      Korea for the period 1984-2013 for adults 30 years and older. Joinpoint
      regression analysis was conducted to determine changes in trends in age
      standardized mortality rates, and age-period-cohort analysis was performed to
      describe trends in colorectal cancer mortality using the intrinsic estimator
      method. RESULTS: In men, the age-standardized mortality rate for colorectal
      cancer increased from 1984 to 2003, and the mortality rates stabilized
      thereafter, whereas the mortality rate of colorectal cancer in women has
      decreased since 2004. The age-specific mortality rate of colorectal cancer
      increased in both men and women over time, whereas decreases in the age-specific
      mortality rate in younger cohorts were observed. In the age-period-cohort
      analysis, old age and recent period were associated with higher mortality for
      both men and women. The birth cohort born after 1919 showed reduced colorectal
      cancer mortality in both men and women. CONCLUSIONS: Our study showed a recent
      decreasing trend in colorectal cancer mortality in women and a stable trend in
      men after 2003-2004. These changes in colorectal cancer mortality may be
      attributed to birth cohort effects.

PMID- 25987068
TI  - Oral contraceptives, abortion and breast cancer risk: a case control study in
      Saudi Arabia.
AB  - BACKGROUND: Several studies have examined the relationship between oral
      contraceptive pill (OCP) use, abortions and breast cancer, with mixed results.
      Hormonal changes associated with OCP use and abortion may increase risk of breast
      cancer over time, but there is a lack of studies studying this association in
      Saudi Arabian women. MATERIALS AND METHODS: We thererfore conducted a case
      control study in 192 women (92 as cases and 100 as controls), aged 30 to 65, and
      collected information on variables including examples related to study objectives
      and those which may confound findings. The Chi square test was used to detect
      associations between various factors and risk of breast cancer. RESULTS: We found
      no evidence of interaction between history of abortion or frequency of abortion
      and breast cancer risk (Chi square=0.422, p =0.420 and 1, p =0.169) respectively.
      Oral contraceptives did not confer risk for breast cancer overall (OR=0.276,
      95%CI 0.092-0.829, p=0.524), while long term use of OCP was associated with
      increased risk of breast cancer (OR=0.297, 95%CI 0.158-0.557, p=0.001), with
      higher association for those who used 10 years or more of OCPs (OR=0.282, 95%CI
      0.095-0.835, p=0.02). Age at first use of OCPs had no effect on breast cancer
      risk (p=0.452) or age at diagnosis (p=0.074). CONCLUSIONS: Prolonged use of OC
      (more than 10 years) may be associated with increased risk of breast cancer in
      Saudi women. Larger population based studies are needed to confirm this finding
      in this population.

PMID- 25987069
TI  - Activities of E6 Protein of Human Papillomavirus 16 Asian Variant on miR-21 Up
      regulation and Expression of Human Immune Response Genes.
AB  - BACKGROUND: Variants of human papillomavirus (HPV) show more oncogenicity than do
      prototypes. The HPV16 Asian variant (HPV16As) plays a major role in cervical
      cancer of Asian populations. Some amino acid changes in the E6 protein of HPV16
      variants affect E6 functions such as p53 interaction and host immune
      surveillance. This study aimed to investigate activities of HPV16As E6 protein on
      modulation of expression of miRNA-21 as well as interferon regulatory factors
      (IRFs) 1, 3, 7 and c-fos. MATERIALS AND METHODS: Vectors expressing E6 protein of
      HPV16As (E6D25E) or HPV16 prototype (E6Pro) were constructed and transfected into
      C33A cells. HCK1T cells expressing E6D25E or E6Pro were established by
      transducing retrovirus-containing E6D25E or 16E6Pro. The E6AP-binding activity of
      E6 and proliferation of the transfected C33A cells were determined. MiR-21 and
      mRNA of interesting genes were detected in the transfected C33A cells and/or the
      HCK1T cells, with or without treatment by culture medium from HeLa cells (HeLa
      CM). RESULTS: E6D25E showed binding activity with E6AP similar to that of E6Pro.
      Interestingly, E6D25E showed a higher activity of miR-21 induction than did E6Pro
      in C33A cells expressing E6 protein. This result was similar to the HCK1T cells
      expressing E6 protein, with HeLa-CM treatment. The miR-21 up-regulation
      significantly corresponded to its target expression. Different levels of
      expression of IRFs were also observed in the HCK1T cells expressing E6 protein.
      Interestingly, when treated with HeLa-CM, IRFs 1, 3 and 7 as well as c-fos were
      significantly suppressed in the HCK1T cells expressing E6D25E, whereas those in
      the HCK1T cells expressing E6Pro were induced. A similar situation was seen for
      IFN-alpha and IFN-beta. CONCLUSIONS: E6D25E of the HPV16As variant differed from
      the E6 prototype in its activities on epigenetic modulation and immune
      surveillance and this might be a key factor for the important role of this
      variant in cervical cancer progression.

PMID- 25987070
TI  - Lenalidomide in treating patients with castration-resistant prostate cancer.
AB  - BACKGROUND: This analysis was conducted to evaluate the efficacy and safety of
      lenalidomide based regimen in treating patients with castration-resistant
      prostate cancer. MATERIALS AND METHODS: Clinical studies evaluating the efficacy
      and safety of lenalidomide based regimens on response and safety for patients
      with castration-resistant prostate cancer were identified using a predefined
      search strategy. A pooled response rate (rate of PSA level decline of >=50%) to
      treatment was calculated. RESULTS: In lenalidomide based regimen, 3 clinical
      studies which including 98 patients with castration-resistant prostate cancer
      were considered eligible for inclusion. These lenalidomide based regimens
      included cisplatin, doxorubicin, or GM-CSF. Pooled analysis suggested that, in
      all patients, the pooled PSA level decline of >=50% was 13.3% (13/98) in
      lenalidomide based regimens. Fatigue, nausea and vomitting were the main side
      effects. No grade III or IV renal or liver toxicity were observed. No treatment
      related death occurred in patients with lenalidomide based regimens. CONCLUSIONS:
      This evidence based analysis suggests that lenalidomide based regimens are
      associated with mild response rate and acceptable toxicities for treating
      patients with castration-resistant prostate cancer.

PMID- 25987071
TI  - Expression of aquaporin 1 in bladder uroepithelial cell carcinoma and its
      relevance to recurrence.
AB  - OBJECTIVES: To explore the expression of aquaporin 1 (AQP1) in bladder
      uroepithelium cell carcinoma (BUCC) and its relevance to recurrence. MATERIALS
      AND METHODS: Tissue samples from 45 BUCC patients who underwent total cystectomy
      or transurethral resection of bladder tumor (TURBT) and from 40 patients with non
      bladder cancers who underwent special detection or treatments were collected. The
      level of expression of AQP1 in BUCC tissues and normal bladder tissues was
      assessed by immunohistochemistry so as to analyze the relevance to pathological
      patterns and time of recurrence in BUCC patients. RESULTS: The expression levels
      of AQP1 normal bladder tissues and BUCC tissues were 2.175+/-0.693 and 3.689+/
      0.701, respectively, and the difference was significant (t=9.99, P<0.0001).
      Marked increase was noted with BUCC histological grade and pathological stage
      (P<0.01). Moreover, the expression of AQP1 was evidently higher in cancerous
      tissues with lymph node metastasis than in those without (P<0.01). With short
      term recurrence, the positive cell expression rate of AQP1 was higher in primary
      tissues, which increased obviously after recurrence. Additionally, the recurrent
      time of BUCC was negatively associated with the positive cell expression rate of
      AQP1 and the difference between the expression of AQP1 before and after
      recurrence (r=-0.843, F=39.302, P=0.000; r=-0.829, F=35.191, P=0.000).
      CONCLUSIONS: AQP1, which reflects the grade, stage, lymph node metastasis and
      recurrence of BUCC, has potential guiding significance in the diagnosis and
      treatment of bladder cancarcinoma.

PMID- 25987072
TI  - Effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma
      stress hormones in surgical patients with thyroid carcinoma.
AB  - BACKGROUND: To investigate the effects of preemptive analgesia with parecoxib
      sodium on haemodynamics and plasma stress hormones in surgical patients with
      thyroid carcinoma. MATERIALS AND METHODS: Fifty-seven patients with thyroid
      carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to
      Taishan Medical University and Binzhou People's Hospital were selected and
      randomly divided into three groups, 19 cases in each group. The control group was
      intravenously injected 0.9% sodium chloride injection before anesthesia
      induction; trial group I was intravenously injected with parecoxib sodium 20 min
      before anesthesia induction; based on trial group I, trial group II was injected
      with parecoxib sodium again 12 h after surgery. The levels of plasma
      norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after
      surgery and changes of haemodynamics before surgery, at the end of surgery and
      12, 24 and 48 h after surgery were compared in the three groups. Besides, visual
      analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery.
      RESULTS: 12 and 24 h after surgery, the levels of plasma NE and Cor in three
      groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in
      trial groups I and II were evidently lower than in control group (P<0.05 or
      P<0.01), and those in trial group II slightly lower than in trial group I. 12 h
      after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups
      I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01),
      but gradually returned to the preoperative level. HR, SBP and diastolic pressures
      (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were
      all lower than in the control group, and significant differences were present
      (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial
      groups I and II were markedly lower than in the control group ((P<0.05 or
      (P<0.01), the scores in trial group II being the lowest. CONCLUSIONS: Combined
      application of parecoxib sodium for preemptive analgesia before anesthesia and
      after surgery can effectively reduce the levels of plasma stress hormones and
      improve analgesic effects in surgical patients with thyroid carcinoma, and
      without conspicuous impact on haemodynamics.

PMID- 25987073
TI  - Knowledge, barriers and attitudes towards breast cancer mammography screening in
      jordan.
AB  - BACKGROUND: Breast cancer is the most common type of cancer in Jordan. Current
      efforts are focused on annual campaigns aimed at increasing awareness about
      breast cancer and encouraging women to conduct mammogram screening. In the
      absence of regular systematic screening for breast cancer in Jordan, there is a
      need to evaluate current mammography screening uptake and its predictors, assess
      women's knowledge and attitudes towards breast cancer and screening mammograms
      and to identify barriers to this preventive service. MATERIALS AND METHODS: This
      cross-sectional study was conducted in six governorates in Jordan through face-
      to-face interviews on a random sample of women aged 40 to 69 years. RESULTS: A
      total of 507 participants with mean age of 46.8+/-7.8 years were interviewed.
      There was low participation rate in early detection of breast cancer practices.
      Breast self-examination, doctor examination and periodic mammography screening
      were reported by 34.9%, 16.8% and 8.6% of study participants, respectively.
      Additionally 3.8% underwent breast cancer screening at least once but not
      periodically, while 87.6% had never undergone mammography screening. Reported
      reasons for conducting the screening were: perceived benefit (50%); family
      history of breast cancer (23.1%); perceived severity (21.2%); and advice from
      friend or family member (5.8%). City residents have shown higher probability of
      undergoing mammogram than those who live in towns or villages. Results revealed
      negative perceptions and limited knowledge of study participants on breast cancer
      and breast cancer screening. The most commonly reported barriers for women who
      never underwent screening were: fear of results (63.8%); no support from
      surrounding environment (59.7); cost of the test (53.4%); and religious belief,
      i.e. Qadaa Wa Qadar (51.1%). CONCLUSIONS: In the absence of regular systematic
      screening for breast cancer in Jordan, the uptake of this preventive service is
      very low. It is essential for the country of Jordan to work on applying regular
      systematic mammography screening for breast cancer. Additionally, there is a need
      for improvement in the current health promotion programmes targeting breast
      cancer screening. Other areas that could be targeted in future initiatives in
      this field include access to screening in rural areas and removal of current
      barriers.

PMID- 25987074
TI  - Relationships of colorectal cancer with dietary factors and public health
      indicators: an ecological study.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iranian
      women and fifth in men. The aims of this study were to investigate the relation
      of dietary factors and public health indicators to its development. MATERIALS AND
      METHODS: The required information (2001-2006) about risk factors was obtained
      from the Non- Communicable Disease Surveillance Centre (NCDSC) of Iran. Risk
      factor data (RFD) from 89,404 individuals (15-64 years old) were gathered by
      questionnaire and laboratory examinations through a cross sectional study in all
      provinces by systematic clustering sampling method. CRC incidence segregated by
      age and gender was obtained from Cancer Registry Ministry of Health (CRMH) of
      Iran. First, correlation coefficients were used for data analysis and then
      multiple regression analysis was performed to control for confounding factors.
      RESULTS: Colorectal cancer incidence showed a positive relationship with diabetes
      mellitus, hypertension, lacking or low physical activity, high education, high
      intake of dairy products, and non-consumption of vegetables and fruits.
      CONCLUSIONS: We concluded that many dietary factors and public health indicators
      have positive relationships with CRC and might therefore be targets of
      preliminary prevention. However, since this is an ecological study limited by
      potential ecological fallacy the results must be interpreted with caution.

PMID- 25987075
TI  - Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and
      "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell
      Lung Cancer.
AB  - BACKGROUND: Systemic inflammatory response was shown to play an important role in
      development and progression of many cancer types and different inflammation-based
      indices were used for determining prognosis. We aimed to investigate the
      prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic
      nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC).
      MATERIALS AND METHODS: NSCLC patients diagnosed in our institution were
      retrospectively reviewed. Demographic and clinicopathologic characteristics were
      recorded. NLR and PNI was calculated before the application of any treatment.
      RESULTS: A total of 138 patients were included in the study. Patients were
      divided into two groups according to NLR (<3.24 or >=3.24) and PNI (<49.5 or
      >=49.5). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the
      group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the
      group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5
      10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5
      50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels
      were evaluated as independent risk factors for overall survival for all patients
      in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively).
      CONCLUSIONS: NLR (>=3.24) and PNI (<49.5) at diagnosis is an independent marker
      of poor outcome in patients with NSCLC. NLR and PNI is an easily measured,
      reproducible prognostic tests that could be considered in NSCLC patients.

PMID- 25987076
TI  - Radioactive seed implantation and lobaplatin chemotherapy are safe and effective
      in treating patients with advanced lung cancer.
AB  - Objecive: To investigate the clinical safety and efficacy of CT-guided 125iodine
      (125I) seed implantation combined with percutaneous intra-tumor injection of
      chemotherapy emulsion of lobaplatin and lipiodol in treating patients with
      advanced lung cancer. MATERIALS AND METHODS: Patients with advanced lung cancer
      and treated with spiral CT-guided 125I seed implantation combined with
      percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and
      lipiodol were recruited. RESULTS: Of the 36 patients, there were 40 nidi in
      total. The contrast-enhanced CT evaluation was conducted 60 d after treatment.
      Response evaluation suggested that 4 patients achieved complete remission (CR),
      24 partial remission (PR), 4 stable disease (SD) and 4 progression disease (PD),
      with a total response rate of 77.8% (28/36). CONCLUSIONS: CT-guided 125I seed
      implantation combined with percutaneous intra-tumor injection of chemotherapy
      emulsion of lobaplatin and lipiodol are safe and effective in treating patients
      with advanced lung cancer.

PMID- 25987077
TI  - Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative
      Analysis on the Tumor Metastasis.
AB  - OBJECTIVE: To explore the expression of RECK and relevant matrix
      metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their
      clinical significance in the tumor metastasis. MATERIALS AND METHODS: Forty-five
      wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical
      resection and confirmed by pathology in Linyi Yishui Central Hospital were
      selected. According to presence and absence of metastasis, both NB and HB samples
      were divided into metastatic group and non-metastatic group, namely NB metastatic
      group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB
      non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix
      metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was
      detected using immunohistochemical method, and the correlation between RECK and
      MT1-MMP, MMP-14 was analyzed. RESULTS: The metastatic rate of NB was dramatically
      higher than that of HB, with statistical significance (P=0.003). The positive
      rate of RECK expression in NB group (30.2%) was slightly lower than in HB group
      (40.0%), but no significant difference was presented (P=0.338). The positive rate
      of MMPs expression in NB metastatic group was evidently higher than in HB
      metastatic group (P=0.024). The results of Spearman correlation analysis revealed
      that the expression of RECK in HB and NB tissues had a significantly-negative
      correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636,
      P=0.000). CONCLUSIONS: In HB and NB tissues, RECK is expressed lowly, while
      relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through
      negative regulation of relevant MMPs.

PMID- 25987078
TI  - Clinical Application of Recombinant Human Endostatin in Postoperative Early
      Complementary Therapy on Patients with Non-small Cell Lung Cancer in Chinese
      Mainland.
AB  - OBJECTIVE: To explore the clinical application of recombinant human endostatin
      (Endostar) in the treatment of patients with non-small cell lung cancer (NSCLC)
      in Chinese mainland. MATERIALS AND METHODS: A total of 75 patients diagnosed as
      NSCLC were randomly divided into control group (37 cases) and treatment group (38
      cases). Control group was treated with postoperative complementary chemotherapy
      containing two-agent platinum protocol on postoperative d21, 3 weeks as a cycle,
      for totally 4~6 cycles. On this basis, treatment group was added with Endostar
      7.5 mg/m2 on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally
      4 cycles. The interval between every two cycles was 7 d. The 5-year progression
      free survival (PFS), 5-year survival time and complications in both groups were
      observed. RESULTS: Compared with control group, the average PFS increased
      evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and
      there was significant difference (P<0.05). And the median PFS was 42.5 months in
      treatment group, obviously longer than that in control group (33.7 months) by 8.8
      months (P<0.05). Additionally, the 5-year overall survival rate (OS), average
      survival time and median survival time (MST) were 47.4%, 50.1 months and 59.3
      months in treatment group, significantly higher than the 29.7%, 42.1 months and
      43.5 months in control group (P<0.05). Only 1 patient showed poor healing of
      surgical wound in treatment group, but no surgery-associated complication was
      found in control group. Moreover, the postoperative complementary therapy
      connected complication rates were 63.2% (24/38) and 59.5% (22/37) in treatment
      group and control group respectively, but there was no significant difference
      (P>0.05). CONCLUSIONS: The application of Endostar combined with sensitive
      platinum-contained chemotherapeutic agents in the postoperative complementary
      chemotherapy can be widely used in clinic because it can significantly prolong
      the long-term survival time of patients with NSCLC.

PMID- 25987079
TI  - Health Beliefs and Breast Self-Examination among Undergraduate Female Students in
      Public Universities in Klang Valley, Malaysia.
AB  - BACKGROUND: Breast cancer is the most frequently occurring cancer in women and
      the most common cause of cancer death worldwide. MATERIALS AND METHODS: A cross
      sectional study was carried out among 792 female undergraduate students in public
      universities in Klang Valley, Malaysia, from January to April 2011. Data were
      collected using a validated questionnaire developed for this study. RESULTS: The
      mean age of respondents was 21.7+/-1.2 years. Most of them were single (96.8%),
      Malay (91.9%) and 150 (19.6%) claimed they had practiced BSE. There was a
      significant differences between performers and non-performers correlated to age,
      marital status, check breast by doctor, and being trained about BSE. Performers
      had lower mean scores for perceived barriers and susceptibility and higher mean
      score for confidence. Stepwise logistic regression analysis yielded four
      significant predictor variables. CONCLUSIONS: Overall our findings indicate that
      the practice of BSE while perceived as being important is not frequently
      practiced among female in Malaysia. Targeted education should be implemented to
      improve early detection of breast cancer.

PMID- 25987080
TI  - Spatial analysis of common gastrointestinal tract cancers in counties of Iran.
AB  - BACKGROUND: Gastrointestinal tract cancers are among the most common cancers in
      Iran and comprise approximately 38% of all the reported cases of cancer. This
      study aimed to describe the epidemiology and to investigate spatial clustering of
      common cancers of the gastrointestinal tract across the counties of Iran using
      full Bayesian smoothing and Moran I Index statistics. MATERIALS AND METHODS: The
      data of the national registry cancer were used in this study. Besides, indirect
      standardized rates were calculated for 371 counties of Iranand smoothed using
      Winbug 1.4 software with a full Bayesian method. Global Moran I and local Moran I
      were also used to investigate clustering. RESULTS: According to the results,
      75,644 new cases of cancer were nationally registered in Iran among which 18,019
      cases (23.8%) were esophagus, gastric, colorectal, and liver cancers. The results
      of Global Moran's I test were 0.60 (P=0.001), 0.47 (P=0.001), 0.29 (P=0.001), and
      0.40 (P=0.001) for esophagus, gastric, colorectal, and liver cancers,
      respectively. This shows clustering of the four studied cancers in Iran at the
      national level. CONCLUSIONS: High level clustering of the cases was seen in
      northern, northwestern, western, and northeastern areas for esophagus, gastric,
      and colorectal cancers. Considering liver cancer, high clustering was observed in
      some counties in central, northeastern, and southern areas.

PMID- 25987081
TI  - Anxiety and Depression among Breast Cancer Patients in an Urban Setting in
      Malaysia.
AB  - BACKGROUND: Breast cancer is one of the most feared diseases among women and it
      could induce the development of psychological disorders like anxiety and
      depression. An assessment was here performed of the status and to determine
      contributory factors. MATERIALS AND METHODS: A cross-sectional study was
      conducted among breast cancer patients at University Kebangsaan Malaysia Medical
      Center (UKMMC), Kuala Lumpur. A total of 205 patients who were diagnosed between
      2007 until 2010 were interviewed using the questionnaires of Hospital Anxiety and
      Depression (HADS). The associated factors investigated concerned socio
      demographics, socio economic background and the cancer status. Descriptive
      analysis, chi-squared tests and logistic regression were used for the statistical
      test analysis. RESULTS: The prevalence of anxiety was 31.7% (n=65 ) and of
      depression was 22.0% (n=45) among the breast cancer patients. Age group (p=
      0.032), monthly income (p=0.015) and number of visits per month (p=0.007) were
      significantly associated with anxiety. For depression, marital status (p=0.012),
      accompanying person (p=0.041), financial support (p-0.007) and felt burden
      (p=0.038) were significantly associated. In binary logistic regression, those in
      the younger age group were low monthly income were 2 times more likely to be
      associated with anxiety. Having less financial support and being single were 3
      and 4 times more likely to be associated with depression. CONCLUSIONS: In
      management of breast cancer patients, more care or support should be given to the
      young and low socio economic status as they are at high risk of anxiety and
      depression.

PMID- 25987082
TI  - Clinical observation on recombinant human endostatin combined with chemotherapy
      for advanced gastrointestinal cancer.
AB  - OBJECTIVE: To explore the clinical efficacy and toxic and side effects of
      recombinant human endostatin (rh- endostatin/endostar) combined with chemotherapy
      in the treatment of advanced gastric cancer. MATERIALS AND METHODS: A total of 70
      patients with advanced gastrointestinal adenocarcioma confirmed by histopathology
      and/or cytological examination were divided into group A (37 patients) and group
      B (33 patients). Patients in group A were given intravenous drip of 15 mg
      endostar added into 500 mL normal saline, once every other day until the
      cessation of chemotherapy or patients' maximal tolerance to chemotherapy.
      Patients in group B received chemotherapy alone. Two groups selected the same
      chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of 180 mg/m2
      irinotecan, intravenous drip of 200 mg/m2 calcium folinate (CF) and 400 mg/m2 5
      fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 400 mg/m2 5-Fu
      for 46 h. FOLFOX4 scheme: intravenous injection of 85 mg/m2 oxaliplatin (L-OHP),
      200 mg/m2 calcium folinate (CF) and 400 mg/m2 5-FU on d1 for 2 h, and then
      continuous intravenous pumping of 2 400 mg/m2 5-Fu for 46 h. XELOX scheme: oral
      administration of 1 500 mg/m2 xeloda (or tegafur 50~60 mg) in twice during d1~14
      and intravenous drip of 135 mg/m2 L-OHP on d1 for 2 h. The modified FOLFOX
      scheme: intravenous injection of 135 mg/m2 L-OHP on d1 for 2 h, 200 mg/m2 CF and
      1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy
      regimens which were same as Group A, but no addition of endostar. Before
      chemotherapy, patients were given intravenous injection of 8 mg ondansetron,
      intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for
      prevention of vomiting, protection of liver and stomach as well as symptomatic
      supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was
      evaluated every 2 cycles. RESULTS: 32 patients in Group A could be evaluated, and
      the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%,
      respectively. 31 patients in Groups could be evaluated, and the RR and DCR were
      32.26% and 54.84%, respectively. The differences between 2 groups were
      significant. The toxic effects include myelosuppression, gastrointestinal
      reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. CONCLUSIONS:
      Preliminary observations show that endostar (once every other day) combined with
      chemotherapy is effective in the treatment of advanced gastrointestinal cancer,
      with low toxic effects, good tolerance, deserving further study.

PMID- 25987083
TI  - Clinical application of serum tumor abnormal protein from patients with gastric
      cancer.
AB  - BACKGROUND: To verify whether serum tumor abnormal protein (TAP) would correlate
      with the responsiveness of palliative chemotherapy in patients with advanced
      gastric cancer, and the variation of conventional serum tumor markers e.g.,
      carcinoembryonic antigen (CEA), antigen 125 (CA125),carbohydrate antigen19-9
      (CA19-9) of adjuvant chemotherapy in patients with early gastric cancer.
      MATERIALS AND METHODS: Patients with histologically confirmed gastric cancer and
      treated with chemotherapy were enrolled into this study. TAP values of these
      patients were determined by detecting abnormal sugar chain glycoprotein in serum,
      combined with the area of agglomerated particles. For patients with advanced
      gastric cancer, responsiveness of palliative chemotherapy was compared with
      variation of TAP and the relation between variation of TAP and tumor markers in
      patients with early gastric cancer was analyzed. RESULTS: Totally 82 gastric
      cancer patients were enrolled into this study. The value of TAP is more closely
      related to responsiveness of palliative chemotherapy for patients with advanced
      gastric cancer. The correlation between TAP and responsiveness to palliative
      chemotherapy is stronger than the correlation between several conventional serum
      tumor markers (CEA, CA125 and CA199) .The variation of TAP was also positively
      correlated with the trend of CA125 in adjuvant chemotherapy. CONCLUSIONS: TAP is
      sensitive in monitoring the responsiveness to palliative chemotherapy in patients
      with advanced gastric cancer. But this result should be confirmed by randomized
      clinical trials for patients with gastric cancer.

PMID- 25987084
TI  - Coenzyme complex decreased cardiotoxicity when combined with chemotherapy in
      treating elderly patients with gastrointestinal cancer.
AB  - OBJECTIVE: To investigate the effect of coenzyme complex on decreasing
      cardiotoxicity in elderly patients with gastrointestinal cancer who were treated
      by chemotherapy. METHODS: From September 2011 to February 2015, we recruited 54
      elderly (with more than 70 years of age) patients with gastrointestinal cancer,
      with advanced disease. Then treated with chemotherapy combined with or without
      coenzyme complex. After two cycles of treatment, the effect of coenzyme complex
      on decreasing cardiotoxicity were evaluated. RESULTS: Chemotherapy was combined
      with coenzyme complex in 32 patients (22man, 10 woman; median age: 74 years,
      range: 70-87 years) without coenzyme complex in 22 patients (15man, 7 woman;
      median age: 73 years, range: 70-80 years) with gastrointestinal cancer. Cardiac
      event was significantly lower in patients treated with chemotherapy combined with
      coenzyme complex (p<0.01). CONCLUSIONS: Coenzyme Complex decreased cardiotoxicity
      when combined with chemotherapy in treating elderly patients with
      gastrointestinal cancer.

PMID- 25987085
TI  - Consanguinity Protecting Effect Against Breast Cancer among Tunisian Women:
      Analysis of BRCA1 Haplotypes.
AB  - The purpose of this study is to assess the effect of consanguinity on breast
      cancer incidence in Tunisia. We conducted a case-control study to evaluate the
      involvement of heterozygote and homozygote haplotypes of BRCA1 gene SNPs
      according to consanguinity among 40 cases of familial breast cancer, 46 cases
      with sporadic breast cancer and 34 healthy controls. We showed significant
      difference in consanguinity rate between breast cancer patients versus healthy
      controls P = 0.001. Distribution of homozygous BRCA1 haplotypes among healthy
      women versus breast cancer patients was significantly different; p=0.02. Parental
      consanguinity seems to protect against breast cancer in the Tunisian population. 

PMID- 25987086
TI  - MDM2 (RS769412) G>A Polymorphism in Cigarette Smokers: a Clue for the
      Susceptibility to Smoking and Lung Cancer Risk.
AB  - Cigarette smoke contains oxidants and free radicals which are carcinogens that
      can induce mutations in humans. Single nucleotide polymorphisms (SNPs) are the
      most frequent genetic alterations found in the human genome. In the present
      study, we have examined the ability of the murine double minute 2 (Mdm2)
      (rs769412) A>G polymorphism in cigarette smokers to predict risk of cancers. Our
      results showed that of smokers, 87% were found with AA genotype, 10% with
      heterozygous AG genotype, and 3% with GG genotype. The heterozygous AG genotype
      was observed in a lower percentage of smokers (10%) as compared to non-smokers
      (18%), whereas, homozygous AA genotype was observed in lower percentage of non
      smokers (81%) as compared to the smokers (87%). The results from present study
      support the association with an allele and AG genotype in non-smokers. However,
      further studies are required to establish the role of Mdm2 (rs769412) C>T in
      cigarettes smokers and diseases. 

PMID- 25987087
TI  - Head and neck squamous cell carcinoma - comparative evaluation of pathological
      parameters in young and old patients.
AB  - BACKGROUND: To evaluate pathological features of head and neck squamous cell
      carcinoma (HNSCC) and to compare these pathological features in patients younger
      and older than 40 years. MATERIALS AND METHODS: All resection specimens of HNSCC
      between 2010 and 2013 evaluated. Tumor characteristics - grade, location (site)
      cervical node status, alongwith presence or absence of extranodal extension,
      lymphovascular invasion, gender and age - were extracted from surgical pathology
      reports. RESULTS: Among these n=19 patients (21.8%) were 40 years or younger and
      n=68 patients (78.2%) were above 40 years of age. The mean age was 34 (20-40
      years) in the younger group and 56 (42-86) in the older group. The most common
      location of HNSCC in both groups was the oral cavity. The analysis of
      histopathological features including grade of tumor, tumor size, extranodal
      extension and comparison between two groups do not show any significant
      difference. CONCLUSIONS: There are no specific pathological characteristics of
      HNSCC in young patients. An interesting observation is that exposure to expected
      risk factors is similar in both groups, in younger patients they have less time
      to act and yet tumors are the same in terms of tumor size, lymph node status and
      lymphovascular invasion. Therefore further research is recommended to look for
      potentiating factors.

PMID- 25987088
TI  - Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of
      Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1
      Cells.
AB  - BACKGROUND: Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted
      protein specifically expressed by endothelial cells during embryogenesis,
      recently was identified as a critical gene in tumor metastasis. Epithelial
      mesenchymal transition (EMT) was found to be closely related with tumor
      progression. Accordingly, it is important to investigate the migration and EMT
      change after knock-down of EGFL7 gene expression in human pancreatic cancer
      cells. MATERIALS AND METHODS: EGFL7 expression was firstly testified in 4
      pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time
      PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1
      cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of
      EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative
      control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze
      the migration of PANC-1 cells. Real-time PCR and western blotting were used to
      detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N
      Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in
      PANC-1, NC- PANC-1, and si-PANC-1 cells, respectively. RESULTS: After successful
      plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference
      in si-PANC-1 group. Meanwhile, migration ability decreased significantly,
      compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial
      phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N
      Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group,
      indicating a reversion of EMT. Also, transcription factors snail and slug
      decreased significantly after RNA interference. CONCLUSIONS: Current study
      suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts
      through transcription factors snail and slug to induce EMT, and further study is
      needed to confirm this issue.

PMID- 25987089
TI  - Aberrant Methylation of the 1p36 Tumor Suppressor Gene RIZ1 in Renal Cell
      Carcinoma.
AB  - BACKGROUND: Retinoblastoma protein-interacting zinc finger gene 1(RIZ1) functions
      as a tumor suppressor. Hypermethylation-mediated RIZ1 silencing has been reported
      in several cancers, but not in renal cell carcinoma (RCC) yet. MATERIALS AND
      METHODS: We examined the RIZ1 expression and methylation in a panel of RCC cell
      lines and 50 primary tumors using semiquantitative/quantitative polymerase chain
      reaction (PCR), methylation specific PCR, and bisulfite sequencing genomic. We
      also explored the relationship between methylation status of RIZ1 and
      clinicopathological features in RCC patients. RESULTS: RIZ1 expression was down
      regulated or lost in OS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines.
      Restored expression of RIZ1 was detected after addition of 5-aza-2'-deoxycytidine
      with/without trichostatin A, suggesting that DNA methylation directly mediates
      its silencing. The RIZ1 expression was significantly reduced in RCCs compared to
      adjacent non-malignant renal samples (P<0.001). Aberrant methylation was detected
      in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent non- malignant renal samples
      (P=0.02). No statistically significant correlation between methylated and
      unmethylated cases with regard to age, gender, pathological stage and grade was
      observed. CONCLUSIONS: RIZ1 expression is down-regulated in human RCC, and this
      down-regulation is associated with methylation. RIZ1 methylation may play a role
      in renal carcinogenesis.

PMID- 25987090
TI  - Prognosis and Clinicopathology of CXCR4 in Colorectal Cancer Patients: a Meta
      analysis.
AB  - The chemokine receptor 4 (CXCR4) has been widely used in diagnosis and prognosis
      of colorectal cancer (CRC). However, there is no current consensus on the impact
      of CXCR4 on CRC patients. The purpose of this study was to evaluate the
      prognostic and clinicopathological importance of CXCR4 in CRC patients.
      Databases, such as PubMed, Cochrane library, CBM and EMBASE updated to 2014 were
      searched to include eligible articles. We analysed correlations between CXCR4
      expression and clinicopathological features and overall survival (OS). A total of
      1, 055 CRC patients from twelve studies were included in the study. The pooled
      odds ratios (ORs) which indicated CXCR4 expression was likely to be associated
      with TNM stage (OR=0.43, CI=0.34-0.55, P<0.00001), lymph node status (OR=2.23,
      CI=1.23-4.05, P=0.008) and vascular invasion (OR=2.21, CI=1.11-4.39, P=0.02).
      Poor overall survival of CRC cancer was found to be significantly related to
      CXCR4 overexpression (hazard ratio (HR) 1.36 CI=1.17-1.59, P<0.0001), whereas
      combined ORs revealed that CXCR4 expression had no correlation with gender or
      differentiation. Based on the published studies, CXCR4 overexpression in patients
      with CRC indicates poor survival outcome and clinicopathological factors. 

PMID- 25987091
TI  - Cancer Screening Adherence of Asian Women According to Biochemically-verified
      Smoking Status: Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Men and women who smoke tend to show less compliance to screening
      guidelines than non- smokers. However, a recent study in Korea showed that self
      reported female smokers constituted less than half of cotinine-verified smokers.
      Therefore, the aim of this study was to identify hidden smokers using cotinine-
      verified method and examine cancer screening behavior according to biochemically
      verified smoking status. MATERIALS AND METHODS: Among 5,584 women aged 30 years
      and older who participated in the Fourth and Fifth Korea National Health and
      Nutrition Examination Survey (KNHANES), 372 (6.66%) hidden smokers were
      identified based on interview responses and verified by urinary cotinine levels.
      We compared cancer-screening behavior (cervical, breast, stomach, and colon
      cancer) of female hidden smokers to that of non-smokers and self- reported
      smokers by cross-sectional analysis. RESULTS: Hidden female smokers had
      significantly lower adherence to breast cancer screening compared to non-smokers
      (aOR (adjusted odds ratio) [95% CI] = 0.71 [0.51-0.98]). Adherence to stomach
      cancer (aOR [95% CI] = 0.75 [0.54-1.03]) and cervical cancer (aOR [95% CI] = 0.85
      [0.66-1.10]) screening was also lower among hidden female smokers compared to non
      smokers. Self-reported (current) smokers showed lowest adherence to cervical
      cancer (aOR: 0.64, 95% CI0.47-0.87), breast cancer (0.47 [0.32-0.68]), stomach
      cancer (0.66[0.46-0.95]), and colon cancer (0.62 [0.38-1.01]) screening compared
      to non-smokers, followed by female hidden smokers, then non-smokers. These lower
      adherence rates of current smokers were attenuated after we incorporated hidden
      smokers into the current smoker group. CONCLUSIONS: Cancer screening adherence of
      female hidden smokers was lower than cotinine-verified non-smokers but higher
      than current smokers. Considering the risk of smoking-related cancer among women,
      identifying hidden smokers is important to encourage appropriate cancer
      screening.

PMID- 25987092
TI  - Effect of home care service on the quality of life in patients with gynecological
      cancer.
AB  - The purpose of the research was to determine the effect of home care service on
      the quality of life in patients with gynecological cancer. This randomized case
      control study was carried out in a womans hospital between September 2011 and
      February 2012. Women undergoing gynecological cancer treatment were separated
      into intervention and control groups, of 35 patients each. The intervention group
      was provided with nursing care service through hospital and home visits (1st,
      12th weeks) within the framework of a specifically developed nursing care plan.
      The control group was monitored without any intervention through the hospital
      routine protocols (1st, 12th weeks). Data were collected using An Interview Form,
      Home Visit Monitoring Form and Quality of Life Scale/Cancer Survivors. Effects of
      home care service on the quality of life in gynecological cancer patients were
      investigated using chi-square tests, McNemar's test, independent t-test and
      ANOVA. This study found that the intervention group receiving home care service
      had a moderately high quality of life (average mean: 6.01+/-0.64), while the
      control group had comparatively lower quality (average mean: 4.35+/-0.79) within
      the 12 week post- discharge period (p<0.05). This study found home care services
      to be efficient in improving the quality of life in patients with gynecological
      cancer. 

PMID- 25987093
TI  - Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia
      Patients in India - Identification of A Novel IDH2 Mutation.
AB  - IDH1/2 mutations which result in alternation in DNA methylation pattern are one
      of the most common methylation associated mutations in Acute myeloid leukaemia.
      IDH1/2 mutations frequently associated with higher platelet level, normal
      cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly
      diagnosed unselected Indian adult AML patients and investigated their correlation
      with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We
      detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2
      c.515_516GG>AA mutation, all the other identified mutations were reported
      mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA
      mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even
      though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically
      abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed
      significant higher platelet count and NPM1 mutations. IDH2 mutated patients
      displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations
      in the IDH1/2 mutated cases showed type A mutation. The present data suggest that
      IDH1/2 mutations are associated with normal cytogenetics and type A NPM1
      mutations in adult Indian AML patients. 

PMID- 25987094
TI  - Genetic Variants in ASCT2 Gene are Associated with the Prognosis of Transarterial
      Chemoembolisation-Treated Early- Stage Hepatocelluar Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent
      malignancies worldwide. Transarterial chemoembolisation (TACE) is the
      standardized therapy for intermediate stage HCC. However, the prognosis for HCC
      patients treated by TACE greatly varies. Thus, there is a critical need for
      finding biomarkers to predict the prognosis of HCC patients. The amino acid
      transporter-2 (ASCT2) is involved in tumorigenesis and progression of many
      malignancies. This study aimed to evaluate the predictive role of two single
      nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC
      patients treated by TACE. MATERIALS AND METHODS: Two functional SNPs (rs3826793
      and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom
      iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients
      treated by TACE. Univariate and multivariate Cox proportional hazards models and
      Kaplan-Meier curves were used for the prognosis analyses. RESULTS: There was no
      significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2
      gene and overall survival of TACE treated HCC patients. However, we demonstrated
      that patients with early stage HCC carrying T genotype in rs2070246 showed better
      OS than those carrying CC genotype (P=0.023). CONCLUSIONS: We demonstrated that
      patients with early stage HCC carrying T genotype in rs2070246 showed better OS
      than those carrying CC genotype.

PMID- 25987095
TI  - Significance and Application of Digital Breast Tomosynthesis for the BI-RADS
      Classification of Breast Cancer.
AB  - BACKGROUND: Full-field digital mammography (FFDM) with dense breasts has a high
      rate of missed diagnosis, and digital breast tomosynthesis (DBT) could reduce
      organization overlapping and provide more reliable images for BI-RADS
      classification. This study aims to explore application of COMBO (FFDM+DBT) for
      effect and significance of BI-RADS classification of breast cancer. MATERIALS AND
      METHODS: In this study, we selected 832 patients who had been treated from May
      2013 to November 2013. Classify FFDM and COMBO examination according to BI-RADS
      separately and compare the differences for glands in the image of the same
      patient in judgment, mass characteristics display and indirect signs. Employ
      Paired Wilcoxon rank sum test was used in 79 breast cancer patients to find
      differences between two examine methods. RESULTS: The results indicated that
      COMBO pattern is able to observe more details in distribution of glands when
      estimating content. Paired Wilcoxon rank sum test showed that overall
      classification level of COMBO is higher significantly compared to FFDM to BI-RADS
      diagnosis and classification of breast (P<0.05). The area under FFDM ROC curve is
      0.805, while that is 0.941 in COMBO pattern. COMBO shows relation of mass with
      the surrounding tissues, the calcification in the mass, and multiple foci clearly
      in breast cancer tissues. The optimal sensitivity of cut-off value in COMBO
      pattern is 82.9%, which is higher than that in FFDM (60%). They share the same
      specificity which is both 93.2%. CONCLUSIONS: Digital Breast Tomosynthesis (DBT)
      could be used for the BI-RADS classification in breast cancer in clinical.

PMID- 25987096
TI  - Clustering asian and north african countries according to trend of colon and
      rectum cancer mortality rates: an application of growth mixture models.
AB  - BACKGROUND: Colorectal cancer is the second most common cause of cancer death
      with half a million deaths per year. Incidence and mortality rates have
      demonstrated notable changes in Asian and African countries during the last few
      decades. In this study, we first aimed to determine the trend of colorectal
      cancer mortality rate in each Institute for Health Metrics and Evaluation (IHME)
      region, and then re-classify them to find more homogenous classes. MATERIALS AND
      METHODS: Our study population consisted of 52 countries of Asia and North Africa
      in six IHME pre-defined regions for both genders and age-standardized groups from
      1990 to 2010.We first applied simple growth models for pre-defined IHME regions
      to estimate the intercepts and slopes of mortality rate trends. Then, we
      clustered the 52 described countries using the latent growth mixture modeling
      approach for classifying them based on their colorectal mortality rates over
      time. RESULTS: Statistical analysis revealed that males and people in high income
      Asia pacific and East Asia countries were at greater risk of death from colon and
      rectum cancer. In addition, South Asia region had the lowest rates of mortality
      due to this cancer. Simple growth modeling showed that majority of IHME regions
      had decreasing trend in mortality rate of colorectal cancer. However, re
      classification these countries based on their mortality trend using the latent
      growth mixture model resulted in more homogeneous classes according to colorectal
      mortality trend. CONCLUSIONS: In general, our statistical analyses showed that
      most Asian and North African countries had upward trend in their colorectal
      cancer mortality. We therefore urge the health policy makers in these countries
      to evaluate the causes of growing mortality and study the interventional programs
      of successful countries in managing the consequences of this cancer.

PMID- 25987097
TI  - Esophageal Cancer in Brunei Darussalam over a three Decade Period: an
      Epidemiologic Study of Trends and Differences between Genders and Racial Groups.
AB  - BACKGROUND: Carcinoma of the esophagus is associated with significant morbidity
      and mortality. The most common subtype is squamous cell carcinoma (SCC). In the
      past three decades, the incidence of SCC has been reported to be decreasing
      whereas esophageal adenocarcinoma (AC) is increasing. This study assessed the
      trend of esophageal cancer in Brunei Darussalam over a three decades period.
      MATERIALS AND METHODS: The National Cancer registry was searched for esophageal
      cancers from 1986 to 2012. Data on age, gender, racial groups (Malays, Chinese,
      Indigenous and foreign nationals) and histology type were collected. The rate
      (ASR) and Age Specific Incidence rate (ASIR) were calculated. RESULTS: The
      predominant tumor type was SCC which accounted for 89% of all esophageal cancer.
      The gender ratio was 2.25: 1 (male: female) and the mean age at diagnosis was
      66.9+/-12.9 years, significantly younger for esophageal AC (57.2+/-16.0) compared
      to SCC (68.1+/-12.0, p<0.05), and among the foreign nationals (p<0.05 for trend).
      The proportions of SCC among all esophageal cancers in the various racial groups
      were: Malays (87.8%), Chinese (100%), Indigenous (100%) and foreign nationals
      (20%). None of the Chinese and Indigenous groups were diagnosed with esophageal
      AC. The overall ASR for esophageal cancer was 2.1/100,000; 2.0/100,000 for SCC
      with a declining trend and 0.17/100,000 for esophageal AC, without any trend
      observed. Among the two major racial groups; the Chinese has higher ASR
      (3.42/100,000) compared to the Malays (ASR 0.95/100,000). CONCLUSIONS: SCC is the
      predominant tumor type of esophageal cancer in Brunei Darussalam and more common
      among the Chinese. There was a declining trend in the incidence of SCC but not
      for esophageal AC.

PMID- 25987099
TI  - Innovation status of gene therapy for breast cancer.
AB  - BACKGROUND: To analyze multi-source data including publications and patents, and
      try to draw the whole landscape of the research and development community in the
      field of gene therapy for breast cancer. MATERIALS AND METHODS: Publications and
      patents were collected from the Web of science and databases of the five major
      patent offices of the world, respectively. Bibliometric methodologies and
      technology are used to investigate publications/patents, their contents and
      relationships. RESULTS: A total of 2,043 items published and 947 patents from
      1994 to 2013 including "gene therapy for breast cancer" were retrieved. The top
      five countries in global publication share were USA, China, Germany, Japan and
      England. On the other hand, USA, Australia, England, South Korea and Japan were
      the main producers of patents. The universities and enterprises of USA had the
      highest amount of publication and patents. Adenovirus- and retrovirus-based gene
      therapies and small interfering RNA (siRNA) interference therapies were the main
      topics both in publications and patents. CONCLUSIONS: The above results show that
      global research in the field of gene therapy for breast cancer is increasing and
      the main participants in this field are USA and Canada in North America, China,
      Japan and South Korea in Asia, and England, Germany, and Italy in Europe. Also,
      this article demonstrates the usefulness of bibliometrics to address key
      evaluation questions and define future areas of research.

PMID- 25987098
TI  - Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive
      Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study.
AB  - BACKGROUND: For HER2 positive metastatic breast cancer (MBC), continuing anti
      HER2 therapy beyond progression is associated with improved outcome. However
      retreatment with trastuzumab after lapatinib progression is controversial. We
      retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+
      metastatic breast cancer patients whose disease progressed after lapatinib.
      MATERIALS AND METHODS: Between October 2010 and May 2013, 54 patients whose
      disease progressed after lapatinib were retreated with trastuzumab-based
      chemotherapy. Efficacy and toxicity results were evaluated retrospectively.
      RESULTS: The median age of patients was 46 (range 27-67). Fourteen patients (26%)
      had metastases at the time of diagnosis. All of the patients had received
      trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two
      lines of trastuzumab. All patients had received lapatinib plus capecitabine. The
      median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial
      metastases were identified in 27 (50%) patients. 53 patients received trastuzumab
      based chemotherapy following lapatinib progression while one patient received
      trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33),
      taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6).
      The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for
      response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease
      progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients.
      At a median follow-up of 9 months (1-39), median progression-free survival was 5
      months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9
      13.0). PFS and OS were not affected by the absence/presence of cranial
      metastases. CONCLUSIONS: Retreatment with trastuzumab-based therapy after
      lapatinib progression showed efficacy in heavily treated MBC patients.

PMID- 25987100
TI  - Early Growth Response Protein-1 Involves in Transforming Growth factor-beta1
      Induced Epithelial-Mesenchymal Transition and Inhibits Migration of Non-Small
      Cell Lung Cancer Cells.
AB  - The zinc finger transcription factor EGR1 has a role in controlling synaptic
      plasticity, wound repair, female reproductive capacity, inflammation, growth
      control, apoptosis and tumor progression. Recent studies mainly focused on its
      role in growth control and apoptosis, however, little is known about its role in
      epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is
      involved in TGF-beta1-induced EMT in non-small- cell lung cancer cells.
      Transforming growth factor (TGF)-beta1 was utilized to induce EMT in this study.
      Western blotting, RT-PCR, and transwell chambers were used to identify phenotype
      changes. Western blotting was also used to observe changes of the expression of
      EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR1 expression.
      We investigated the change of migration to evaluate the effect of EGR 1 on non
      small-cell lung cancer cells migration by transwell chambers. After stimulating
      with TGF-beta1, almost all A549 cells and Luca 1 cells (Non-small-cell lung
      cancer primary cells) changed to mesenchymal phenotype and acquired more
      migration capabilities. These cells also had lower EGR 1 protein expression.
      Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell
      migration capabilities significantly after adding TGF-beta1. These data showed an
      important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well
      as migration. 

PMID- 25987101
TI  - Important doctor-patient communication ability for chinese medical students.

PMID- 25987102
TI  - The failure of immune checkpoint blockade in multiple myeloma with PD-1
      inhibitors in a phase 1 study.

PMID- 25987103
TI  - Caregivers' three-cornered hats: Their tricornes.

PMID- 25987104
TI  - Predictors of anxiety among pregnant New Zealand women hospitalised for
      complications and a community comparison group.
AB  - OBJECTIVE: to investigate predictors of anxiety for women experiencing
      hospitalisation during pregnancy and a comparison group of pregnant women (with
      or without medical complications) in the community. DESIGN: correlational, cross
      sectional observational questionnaire study. SETTING: regional antenatal
      inpatient unit and community-based settings in New Zealand in 2009 and 2010.
      PARTICIPANTS: 118 pregnant women in hospital and 114 pregnant women in community.
      MEASUREMENTS AND FINDINGS: women in hospital and community groups completed a
      battery of questionnaires on pregnancy and health history, life events, anxiety,
      optimism, coping, and relationship factors. Midwives caring for the women
      provided ratings of health status and psychological distress. Both groups of
      women had scores on state anxiety significantly above local norms; women in the
      hospital were significantly higher than those in the community on state anxiety
      and worry about their pregnancy. The groups did not differ on factors such as
      life events, optimism, and coping self-efficacy. Ratings of health and distress
      made by women and their midwives showed poor agreement. Predictors of acute
      anxiety differed across the groups: for hospitalised women, anxiety was predicted
      by their rating of their health and their dispositional optimism; for women in
      the community, anxiety was predicted by stressful life events, dispositional
      optimism, and coping self-efficacy. KEY CONCLUSIONS: many women hospitalised
      during pregnancy are extremely anxious, and those most vulnerable are those who
      are less optimistic and see their health as poor. Health care professionals may
      not be aware of how anxious women are, and women and their hospital caregivers
      had poor agreement on ratings of the woman's health status. IMPLICATIONS FOR
      RESEARCH AND PRACTICE: women hospitalised during pregnancy are at risk for high
      levels of anxiety. Midwives are well placed to help women by recognising their
      distress, supporting informed optimism, and guiding women toward realistic coping
      strategies and using existing social support networks. Research is needed on
      strategies for implementation and effectiveness of brief interventions to support
      women to manage anxiety and stress during pregnancy both in hospital and in the
      community.

PMID- 25987105
TI  - Neuroendocrine Neoplasms of the Major Duodenal Papilla With Focus on
      Histopathological Features and Prognosis.
AB  - Neuroendocrine neoplasms (NENs) are generally indolent and progress slowly.
      However, NENs of major duodenal papilla are uncommon. We retrospectively assessed
      relevant clinicopathological findings in 9 consecutive patients treated for major
      duodenal papilla NENs by pancreaticoduodenectomy in our hospital from 2009 to
      2013. Eight of the 9 patients (89%) presented with painless obstructive jaundice
      and one with intermittent fever, attributable to pancreatitis, without jaundice.
      The diagnostic accuracy was 75% (6/8) for biopsies obtained under duodenoscope
      guidance. Enhanced multidetector computed tomography detected 89% (8/9) of
      tumors. Patients with uncertain preoperative diagnoses all underwent
      intraoperative frozen section pathological diagnosis. Tumor cells extended to at
      least the muscularis propria in all patients. There were 5 neuroendocrine tumors,
      2 neuroendocrine carcinomas, and 2 mixed adenoneuroendocrine carcinomas. Two, 4,
      and 3 cases were grades 1, 2, and 3, respectively. Grade 3 tumor patients had
      poor prognoses with tumor recurrence or metastasis within 2 months and all died
      within 1 year. The overall survival rate (1 year) of grade 3 was lower than in
      grades 1 and 2 (P < .05). Patients with grade 1 tumors had a similar prognosis to
      grade 2 (P > .05). To date, only 4 cases of this tumor have been reported in the
      Chinese literature. The prognosis can be predicted accurately by
      histopathological features accordingly to the World Health Organization 2010
      classification. Multiple imaging techniques and pathological examination should
      be carried out appropriately to diagnose the disease early.

PMID- 25987106
TI  - Combining antiangiogenic therapy and radiation in nasopharyngeal carcinoma.
AB  - Radiation therapy is the primary treatment in nasopharyngeal carcinoma (NPC), and
      the effect of radiation therapy is strongly related to the oxygen content of
      cancer cells. That means, it is imperative to balance the interactions between
      radiotherapy and anti-angiogenesis therapy when giving combination therapy to
      improve clinical outcomes. The complicated mechanisms between antiangiogenic
      agents and radiation involve many interactions between the cancer cells,
      vasculature, and cancer stroma. The proliferation and metastasis of cancer
      depends on angiogenesis, while rapid growth of cancers will cause hypoxia, which
      contributes to radioresistance. Antiangiogenic agents can modulate the cancer
      blood flow and oxygenation through target cancer vasculature, leading to
      increased radiosensitivity. This study discusses the mechanisms of the
      synergistic effect of the antiangiogenic therapy with radiation therapy in
      metastatic NPC, and reviews the data supporting this strategy as a promising
      treatment for metastatic NPC. 

PMID- 25987107
TI  - Antibodies against human platelet alloantigens and human leucocyte antigen class
      1 in Saudi Arabian multiparous women and multi-transfused patients.
AB  - OBJECTIVES: To determine the frequency of alloimmunization against human platelet
      antigens (HPAs) and human leucocyte antigen class 1 (HLA1) in multiparous women
      and multi-transfused patients.   METHODS: This prospective study was conducted
      between January and August 2013, on 50 multiparous women with no history of
      previous blood transfusion recruited from the Obstetrics and Gynecology Clinic,
      and 50 patients, who received multiple platelet transfusions, recruited from the
      Hematology/Oncology Ward, King Khalid University Hospital, Riyadh, Saudi Arabia.
      RESULTS: The frequency of alloimmunization among multiparous pregnant women was
      76%, as follows: 16% against HLA1 only, 8% against HPAs only, 52% against both
      HPAs and HLA1 antigens. In multi-transfused patients, the rate of
      alloimmunization was 42% as follows: 2% against HLA1 only, 22% against HPAs only,
      18% against both HPAs and HLA1 antigens. The frequency of alloimmunization
      increases with the number of pregnancies, but not with the number of platelet
      transfusions. CONCLUSION: Alloimmunization against HPAs and HLA1 is very common
      among Saudi multiparous women and multi-transfused patients, which encourages the
      search for the extent of the possible complications in the fetus and newborn and
      in multitransfused patients and how to prevent their occurrence.

PMID- 25987108
TI  - Association of total antioxidants level with glaucoma type and severity.
AB  - OBJECTIVES: To compare the mean total antioxidant status (TAS) among 3 glaucoma
      types, namely: pseudoexfoliation glaucoma (PEG), primary open angle glaucoma
      (POAG), and primary angle closure glaucoma (PACG), and study its potential
      association with various clinical glaucoma-parameters.   METHODS: In this case
      control study, plasma samples were obtained between September 2013 and October
      2014 from 340 glaucoma patients (PEG [n=54]; POAG [n=147]; PACG [n=139]), and 351
      controls of matching age, gender, ethnicity, and 5 different systemic co
      morbidities from King Abdulaziz University Hospital, Riyadh, Saudi Arabia. The
      TAS in all samples was determined by a colorimetric-based assay.   RESULTS: The
      mean+/-standard deviation of TAS was significantly lower among cases: 0.77+/-0.32
      than controls: 1.1+/-0.22, p less than 0.0001. Moreover, the TAS levels were
      significantly different across the 3 types of glaucoma: 0.86+/-0.24 in PEG,
      0.47+/-0.32 in POAG, and 0.98+/-0.41 in PACG (all p less than 0.0001). In
      addition, there was a significant correlation between TAS and age at onset
      (Pearson correlation coefficient [R] 0.17, p less than 0.0001), cup/disc ratio
      (R: -0.13, p=0.004), and number of anti-glaucoma medications (R: -0.16, p=0.001).
      CONCLUSION: Our findings provide evidence that plasma TAS levels are decreased
      in patients with glaucoma, more so in POAG and PEG than PACG, supporting the
      hypothesis that decreased antioxidative defense and/or increased oxidative stress
      may have a critical role in the pathogenesis of glaucoma.

PMID- 25987109
TI  - Triaging self-referred patients attending ophthalmic emergency room.
AB  - OBJECTIVES: To introduce an effective and safe ophthalmic triaging system to be
      used by non-ophthalmologists.   METHODS: A modified scoring triage system with
      more relevant clinical symptoms and signs from a previously published Rome Eye
      Scoring System for Urgency and Emergency (RESCUE) was evaluated over a 2-month
      period. The study was conducted following a prospective cohort design between
      March and September 2014 at King Abdulaziz University Hospital (KAUH), Riyadh,
      Saudi Arabia. Only self-referred patients were included. Its reliability in
      differentiating urgent and semi-urgent conditions from non-urgent conditions,
      identifying patients who need immediate intervention, and decreasing the waiting
      time were tested using Mann Whitney U test.   RESULTS: A total of 531 patients
      were included in the validation phase to evaluate the triaging system
      reliability, and 824 patients were included in the implementation phase (applying
      the system in the ophthalmology emergency room). The sensitivity to differentiate
      urgent and semi-urgent conditions from non-urgent conditions improved from 90.7
      to 98.7%, while the specificity decreased from 97.2 to 87% compared with RESCUE.
      The sensitivity in differentiating urgent conditions from semi-urgent and non
      urgent conditions was 99%, and the specificity was 90%. Mean waiting time reduced
      from 58.23 minutes to 46 minutes (p=0.014), and the median waiting time reduced
      from 46 minutes to 33 minutes (p=0.009).   CONCLUSION: This triage system appears
      to be safe and effective in recognizing the urgency of different ophthalmic
      conditions, reducing unnecessary ophthalmic emergency load and waiting time
      significantly.

PMID- 25987110
TI  - Hyperlipidemia in rheumatoid arthritis patients in Saudi Arabia. Correlation with
      C-reactive protein levels and disease activity.
AB  - OBJECTIVES: To determine the prevalence of hyperlipidemia in patients from Saudi
      Arabia with rheumatoid arthritis (RA), and to investigate its relationship with C
      reactive protein level and disease activity. METHODS: A cross-sectional 3-year
      study was conducted on RA patients at King Abdulaziz University Hospital, Saudi
      Arabia between January 2011 and December 2013. Lipid profiles were determined
      following 12-hour overnight fasting, and the association of lipid profiles with C
      reactive protein (CRP) levels and disease activity was determined. RESULTS: This
      study involved a total of 180 RA patients (mean age: 40.49+/-12.19 years). These
      subjects displayed a high prevalence of elevated total cholesterol (55.1%), and
      low-density lipoprotein cholesterol (51.2%). Notably, we detected a significant
      association between increased total cholesterol and high CRP levels (p=0.002).
      Moreover, we observed a positive correlation between total cholesterol and
      disease activity, as measured using the 28-Joint Disease Activity Score index
      (r=0.23, p=0.036). CONCLUSIONS: Hyperlipidemia is common among RA patients and is
      significantly associated with CRP levels and disease activity. Our findings
      emphasize the need to raise awareness among healthcare professionals regarding
      the development of hyperlipidemia when RA is active.

PMID- 25987111
TI  - Characterization of thyroid function and antithyroid antibody tests among Saudis.
AB  - OBJECTIVE: To determine the reference intervals for thyroid function tests and
      the prevalence of thyroid autoimmunity in the Saudi population.   METHODS: A
      cross-sectional prospective study was conducted in King Khalid University
      Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical
      examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine
      (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence
      Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies
      were measured using enzyme-linked immunosorbent-assay. Subjects with previous or
      a family history of thyroid disorders, those taking medications affecting thyroid
      function, pregnant or lactating women, and those with goiter were excluded.
      Individuals with positive antibodies were excluded from the final analysis of the
      TSH reference range, but were used to determine the prevalence of thyroid
      autoimmunity.   RESULTS: Out of 337 Saudi subjects initially screened, 132 (aged
      13-60 years) were candidates for reference calculation, the mean+/-standard
      deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96+/-0.9 (0.59
      4.37), for FT4 (pmol/L) was 15.47+/-1.83 (12.04-19.13), and for FT3 (pmol/L) was
      5.22+/-0.7 (4.07-6.76). The TSH was higher in the antibodies positive group
      (2.5+/-1.17 mIU/L) compared with the negative one (1.96+/-0.9 mIU/L) (p less than
      0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies. 
      CONCLUSION: The TSH reference range was similar to laboratory references.
      Thyroid antibodies were prevalent in Saudis, necessitating further work in larger
      scale studies.

PMID- 25987112
TI  - Increasing trends in kidney cancer over the last 2 decades in Saudi Arabia.
AB  - OBJECTIVES: To examine the trends of kidney cancer over the last 2 decades in a
      subset of a Saudi Arabian population.   METHODS: We conducted a retrospective
      study in a tertiary care center including all adult patients with primary kidney
      cancer who presented and were managed between 1990 and 2010. The time period was
      split into 4 quartiles, and variables tested and compared using chi-square, T
      test, and Kaplan-Meier curves for survival.   RESULTS: The total was 215 patients
      with a mean age of 57.8 years. There was an increase in the number of kidney
      cancer cases over the last 2 decades. There was no significant difference in the
      mode of presentation or stage distribution between quartiles. A significant
      change was observed in the management towards minimally invasive and nephron
      sparing surgeries (p less than 0.001). There was no change in recurrence-free and
      disease-specific survival over the last 20 years.   CONCLUSIONS: There have been
      an increasing number of kidney cancer patients over the last 2 decades with no
      observed migration towards more incidental and low stage tumors as compared with
      developed countries.

PMID- 25987113
TI  - Impact of maternal and neonatal factors on parameters of hematopoietic potential
      in umbilical cord blood.
AB  - OBJECTIVES: To determine characteristics of laboratory parameters of
      hematopoietic potential in umbilical cord blood and their association with
      maternal and neonatal factors.  METHODS: This prospective analysis was performed
      on 206 umbilical cord blood donations (50-200 ml) from King Faisal Specialist
      Hospital and Research Centre, Riyadh, Saudi Arabia between January and September
      2014. Samples were processed and analyzed for total nucleated cells (TNC's),
      cluster designation (CD)45+, CD34+ counts, nucleated red blood cells (NRBCs)
      count, and viability testing.   RESULTS: Most of the study participants (63.6%)
      were on their first 3 deliveries and from women with age between 17 and 30 years
      (80.6%). The donated volume was 50.4-192.4 ml, TNCs ranged from 500.2*106 to
      9430.3 *106 cells, and CD34+ cells ranged from 1.25*106 to 12.82*106/unit. The
      volume was positively affected by bigger birth weight of the baby (p less than
      0.0001), larger placenta (p=0.001), TNCs (p less than 0.0001), CD34+ (p less than
      0.0001), NRBCs (p less than 0.0001), and viability (p=0.002). There were no
      statistically significant differences between baby boys and girls for laboratory
      variables.   CONCLUSION: In the selection and identification of a possible donor
      of umbilical cord blood, several maternal and neonatal factors should be
      considered, as younger maternal age, neonatal birth weight greater than 3300
      grams, larger placental size, and first or second-born babies, were shown to be
      associated with higher TNCs, CD34+, CD45+, NRBCs, and viability.

PMID- 25987114
TI  - Pediatric hypertension in the Eastern Province of Saudi Arabia.
AB  - OBJECTIVES: To compare the levels of blood pressure (BP) between male and female
      adolescents in the Eastern Province of Saudi Arabia and reference percentiles for
      Saudi adolescents. A secondary aim was to explore the distribution of BP among
      the participants based on age and gender.   METHODS: This cross-sectional study
      was conducted among 146 boys and girls attending intermediate  and secondary
      schools in 2 regions (Al-Mallaha and Al-Mubarraz) in the Eastern Province of
      Saudi Arabia.  Weight, random blood glucose, and BP were collected by a team of
      health educators in the morning of the school day between April and May 2014.  
      RESULTS: Of the current sample of adolescents originally from the Eastern
      Province, 30% had systolic blood pressure (SBP) of >=140 mm Hg and 22% had
      diastolic blood pressure of >=90 mm Hg. For girls between 13 and 16 years old,
      the SBP was greater than the 95th percentile of Saudi national norms.
      Participants were classified by gender and school stage, and one-way analysis of
      variance showed significant differences in the means of SBP between intermediate
      boys (127+/-2.5 mm Hg) and secondary boys (136+/-2.1 mm Hg) (p less than 0.05),
      and between intermediate boys and intermediate girls (138+/-1.6 mm Hg) (p less
      than 0.01).   CONCLUSION: The increased level of BP among adolescents originally
      from the Eastern Province raises the need to update the current BP nomograms,
      considering possible differences for specific geographic areas across the
      country. Implementing therapeutic life style management in girls' schools is
      recommended.

PMID- 25987115
TI  - Risk factors of diarrhea in children under 5 years in Al-Mukalla, Yemen.
AB  - OBJECTIVES: To assess the risk factors associated with diarrhea among children
      below 5-years-old in Mukalla, Yemen, and compare with other studies.   METHODS:
      We conducted a case-control study on 200 children (100 cases and 100 controls)
      who attended the Maternity and Child Hospital, outpatient-clinics, and the
      Primary Health Care Centers in Al-Mukalla, Hadhramout, Yemen between February and
      April 2013.   RESULTS: We found that the significant risk factors associated with
      diarrhea were crowded housing (odds ratio [OR] 2.02; p=0.02; confidence interval
      [CI] 1.03-4.01), incomplete vaccination of the child (OR=2.02; p=0.027; CI: 1.08
      3.8), and recurrent diarrheal illness during the last 3 months (OR=6.61; p=0.001;
      CI: 3.41-12.90).   CONCLUSION: Diarrheal diseases are strongly associated with
      incomplete vaccination, recurrent diarrheal disease, and crowded housing.

PMID- 25987116
TI  - Prevalence of spinal disorders and their relationships with age and gender.
AB  - OBJECTIVES: To establish the period prevalence of spinal disorders referred to
      physical therapy in a university hospital over a 3-year period, and to determine
      the relationships of common spinal disorders with patients' age and gender.  
      METHODS: This retrospective study was conducted in the Physical Therapy
      Department, King Fahd Hospital of the University, Dammam, Saudi Arabia. Computer
      data of all new electronic referrals from January 2011 to December 2013 were
      retrieved and reviewed. The computer data included demographic information,
      referring facility, and diagnosis/disorder.   RESULTS: One thousand six hundred
      and sixty-nine (28.1%) of all referred patients (5929) had spinal disorders. The
      most common disorders affected the lumbar spine (53.1%) and cervical spine
      (27.1%), and pain was the most common disorder. Neck pain (60.5%) was more common
      in patients less than 30 years old (p less than 0.001). Cervical spondylosis was
      common (~30%) in the greater than 30 age groups. Spondylosis and low back pain
      were more prevalent in women (7.8% and 76.2%) than in men (73.9% and 3.3%).  
      CONCLUSION: Spinal disorders were common compared with other disorders. Low back
      pain and neck pain were the most common spinal disorders. Age and gender were
      weakly related to some of the disorders that affected the lumbar and cervical
      spine.

PMID- 25987117
TI  - Satisfaction of medical students with simulation based learning.
AB  - OBJECTIVES: To evaluate medical students' satisfaction with simulation based
      learning strategy (SBL).   METHODS: A cross-sectional survey was conducted
      between October  and November 2013 at the College of Medicine, King Saud bin
      Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. All third and
      fourth year medical students (n=185) both males and females were included. A self
      developed questionnaire on the effect of SBL was used. Items included were
      related to knowledge, skill, environment, resources, and faculty. The
      questionnaire was validated by an expert reviewer, and the reliability was
      calculated for all the questionnaire items. Responses were measured on a 5 point
      Likert-type scale, and statistical analysis was carried out.   RESULTS: The
      response rate for this study was 62% (n=115). The alpha coefficient for all items
      was 0.73. Overall, respondents from both years' students were satisfied with
      teaching strategy, use of mannequins, and learning environment. The challenges
      reported were lack of skill-laboratories facilities, students' cooperation,
      allocated time for skill-laboratories, and knowledge of instructor. There was a
      small, but significant difference between the satisfaction scores among genders
      (p=0.001). Whereas no difference was identified between the participants' scores
      on satisfaction with SBL and year of education (p=0.62).   CONCLUSION: Although
      there were few challenges, most of the students were satisfied that SBL improved
      their knowledge retention, skills, and communication.

PMID- 25987119
TI  - Medical therapy of a left-sided native valve endocarditis with neurologic
      sequela.
AB  - Infective endocarditis could present with a plethora of signs and symptoms. Among
      the rarity of its presentation is acute confusion associated with neurological
      deficits, mimicking stroke especially in the young population. We report a case
      of a 33-year-old young man with acute right-sided hemiparesis and confusion 2
      weeks after  tooth extraction. The brain CT and MRI was consistent with new
      infarction on the left middle and anterior cerebral arteries' territory.
      Echocardiography unveiled the existence of posterior mitral valve leaflet
      vegetation. Blood culture grew Group B beta-haemolytic Streptococcus, sensitive
      to penicillin. Two weeks of intravenous gentamicin with 6 weeks of intravenous
      benzylpenicillin were administered. In this case report, we highlight the
      importance of recognition of infective endocarditis in a young patient presenting
      with cerebrovascular accident following tooth extraction. 

PMID- 25987118
TI  - Prevalence of dental caries in primary and permanent teeth and its relation with
      tooth brushing habits among schoolchildren in Eastern Saudi Arabia????????.
AB  - OBJECTIVES: To determine the prevalence of dental caries in the primary and
      permanent teeth, and evaluate the brushing habits of school children in Dammam,
      Kingdom of Saudi Arabia (KSA).  Methods. This study was conducted at Dammam, KSA.
      Oral examination of the participants was conducted from February to May 2014. The
      total sample size for this cross-sectional study was 711. There were 397 children
      between the age of 6-9 years, who were examined for primary teeth caries, and 314
      between the age 10-12 years were examined for permanent teeth caries. Primary and
      permanent dentitions were studied for decayed, missing, and filled teeth (dmft
      [primary teeth], DMFT [permanent teeth]).   RESULTS: The overall prevalence of
      dental caries in primary and permanent teeth was almost 73% (n=711). Among the 6
      9-year-old, the prevalence of caries was approximately 78% (n=397) whereas, among
      the 10-12-year-old children, it was approximately 68% (n=314). Mean dmft value
      among the 6-9-year-olds was 3.66+/-3.13 with decayed (d) component of 3.28+/
      2.92, missing (m) component of 0.11+/-0.69, and filled (f) component of 0.26+/
      0.9. Mean DMFT value among the 10-12-year-old children was 1.94+/-2.0 with
      decayed (D) component of 1.76+/-1.85, missing (M) component of 0.03+/-0.22, and
      filled (F) of component 0.15+/-0.73. Daily tooth brushing had a positive effect
      on caries prevention, and this effect was statistically significant for caries in
      primary teeth.   CONCLUSION: Although the prevalence of dental caries in primary
      and permanent teeth was not found to be as high as other researchers reported
      from different cities of KSA, still the prevalence was high considering the World
      Health Organization future oral health goals. Awareness should be provided to
      students, as well as, teachers and parents regarding the importance of good
      brushing habits and regular dental visits.

PMID- 25987120
TI  - Saddle pulmonary embolus and bronchiolitis obliterans with organizing pneumonia
      develop simultaneously after first cyclophosphamide, methotrexate, 5FU
      chemotherapy for breast cancer.
AB  - A 62-year-old woman underwent a right mastectomy with axillary node dissection
      for a poorly differentiated ductal carcinoma. One month later, she underwent a
      left nephrectomy for a renal cell carcinoma. Two weeks after, she received her
      first cycle of cyclophosphamide, methotrexate, and 5FU (CMF) as a part of her
      breast cancer treatment. We describe an unusual case of non-occlusive saddle
      pulmonary embolus with extensive bilateral deep vein thrombosis and severe
      bronchiolitis obliterans with organizing pneumonia developing simultaneously
      after the first CMF chemotherapy for breast cancer. 

PMID- 25987121
TI  - Assessment of knowledge of celiac disease among health care professionals.
AB  - OBJECTIVES: To assess knowledge of celiac disease among medical professionals
      (physicians).   METHODS: We conducted a cross-sectional survey of hospital-based
      medical staff in primary, secondary, and tertiary care public, and private
      hospitals in Riyadh, Saudi Arabia (KSA). We carried out the study between January
      2013 and January 2104 at King Khalid University Hospital, King Saud University,
      Riyadh, KSA. A pretested questionnaire was distributed to the potential
      participants. A scoring system was used to classify the level of knowledge of
      participants into 3 categories: poor, fair, and good.  RESULTS: A total of 109
      physicians completed the survey and of these participants, 86.3% were from public
      hospitals, and 13.7% from private hospitals; 58.7% were males. Of the physicians,
      19.2% had poor knowledge. Interns and residents had fair to good knowledge, but
      registrars, specialists, and even the consultants were less knowledgeable of
      celiac disease.   CONCLUSION: Knowledge of celiac disease is poor among a
      significant number of physicians including consultants, which can potentially
      lead to delays in diagnosis. Educational programs need to be developed to improve
      awareness of celiac disease in the health care profession.

PMID- 25987122
TI  - Dimensions of physical wellness among medical students of public and private
      medical colleges in Pakistan.
AB  - OBJECTIVES: To determine adherence to dimensions of physical wellness among
      medical students of public and private medical colleges in Pakistan.   METHODS:
      This cross-sectional study was carried out from January to July 2011 among 820
      students of private and public medical colleges in Karachi, Pakistan.   RESULTS:
      Overall, medical students scored low in dimensions of physical wellness. Private
      medical colleges students were fond of vigorous activities such as aerobics and
      swimming, whereas public medical colleges students were involved in moderate
      intensity activities such as walking and use of stairs (p less than 0.0001).
      Private students reported to consume more fast food (p=0.0001), had less sleep
      (p=0.0001), but attended regular annual medical checkups (p=0.009) as compared
      with their public institute counterparts. Safe practices such as avoidance of
      tobacco were almost the same.   CONCLUSION: Comprehensive adherence to all
      dimensions of physical wellness was lacking among medical students.

PMID- 25987123
TI  - Critical care service in Saudi Arabia.

PMID- 25987124
TI  - Localized gigantism.

PMID- 25987125
TI  - A rare case of multilocus brain abscess due to Entamoeba histolytica infection in
      a child.

PMID- 25987126
TI  - Pathological fracture due to Paget's disease of bone.

PMID- 25987127
TI  - Celecoxib increases EGF signaling in colon tumor associated fibroblasts,
      modulating EGFR expression and degradation.
AB  - We previously demonstrated that non-toxic doses of Celecoxib induced the
      immediate phosphorylation of Erk1-2 in colon tumor associated fibroblasts (TAFs),
      increasing their responsiveness to epidermal growth factor (EGF). We have now
      identified two concomitant mechanisms explaining the EGF-Celecoxib cooperation.
      We found that a 24-48h Celecoxib priming increased EGF receptor (EGFR) mRNA and
      protein levels in colon TAFs, promoting EGF binding and internalization.
      Celecoxib-primed TAFs showed a reduced EGFR degradation after EGF challenge. This
      delay corresponded to a deferred dissociation of EEA1 from EGFR positive
      endosomes and the accumulation of Rab7, pro Cathepsin-D and SQSTM1/p62,
      suggesting a shared bottleneck in the pathways of late-endosomes/autophagosomes
      maturation. Celecoxib modulated the levels of target proteins similarly to the
      inhibitors of endosome/lysosome acidification Bafilomycin-A1 and NH(4)Cl.
      Cytoplasmic vesicles fractionation showed a reduced maturation of Cathepsin-D in
      late endosomes and an increased content of EGFR and Rab7 in lysosomes of
      Celecoxib-treated TAFs.Our data indicate a double mechanism mediating the
      increased response to EGF of colon TAFs treated with Celecoxib. While EGFR
      overexpression could be targeted using anti EGFR drugs, the effects on endosome
      trafficking and protein turnover represents a more elusive target and should be
      taken into account for any long-term therapy with Celecoxib.

PMID- 25987128
TI  - EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with
      induction by AEG-1 via NF-kappaB signaling pathway.
AB  - The role of epidermal growth factor-containing fibulin-like extracellular matrix
      protein 1 (EFEMP1) in osteosarcoma remains unknown. Then applying EFEMP1 siRNA,
      plasmids transfection and adding purified EFEMP1 protein in human osteosarcoma
      cell lines, and using immunohistochemistry on 113 osteosarcoma tissues,
      demonstrated that EFEMP1 was a poor prognostic indicator of osteosarcoma; EFEMP1
      was specifically upregulated in osteosarcoma and associated with invasion and
      metastasis in vitro and in vivo. At the same time, we found a direct regulatory
      effect of EFEMP1 on MMP-2. Moreover, we firstly found the marked induction of
      EFEMP1 by oncogenic AEG-1. And EFEMP1 expression was inhibited by the selective
      inhibitor of NF-kappaB (PDTC) in osteosarcoma cells. Then we thought that NF
      kappaB pathways might be one of the effective ways which EFEMP1 was induced by
      AEG-1. Thus, we suggested that EFEMP1 played a part as the mediator between AEG-1
      and MMP-2. And NF-kappaB signaling pathway played an important role in this
      process. In summary, EFEMP1 was associated with invasion, metastasis and poor
      prognosis of osteosarcoma patients. EFEMP1 might indirectly enhance the
      expression of MMP-2, providing a potential explanation for the role of AEG-1 in
      metastasis. NF-kappaB pathways might be one of the effective ways which EFEMP1
      was induced by AEG-1.

PMID- 25987132
TI  - Low-temperature solution-processed tin oxide as an alternative electron
      transporting layer for efficient perovskite solar cells.
AB  - Lead halide perovskite solar cells with the high efficiencies typically use high
      temperature processed TiO2 as the electron transporting layers (ETLs). Here, we
      demonstrate that low-temperature solution-processed nanocrystalline SnO2 can be
      an excellent alternative ETL material for efficient perovskite solar cells. Our
      best-performing planar cell using such a SnO2 ETL has achieved an average
      efficiency of 16.02%, obtained from efficiencies measured from both reverse and
      forward voltage scans. The outstanding performance of SnO2 ETLs is attributed to
      the excellent properties of nanocrystalline SnO2 films, such as good
      antireflection, suitable band edge positions, and high electron mobility. The
      simple low-temperature process is compatible with the roll-to-roll manufacturing
      of low-cost perovskite solar cells on flexible substrates. 

PMID- 25987129
TI  - The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma.
AB  - Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis and are poorly
      understood brain cancers. Receptor tyrosine kinases stabilized by neuron-glial
      antigen 2 (NG2) protein are known to induce gliomagenesis. Here, we investigated
      NG2 expression in a cohort of DIPG specimens (n= 50). We demonstrate NG2
      expression in the majority of DIPG specimens tested and determine that tumors
      harboring histone 3.3 mutation express the highest NG2 levels. We further
      demonstrate that microRNA 129-2 (miR129-2) is downregulated and hypermethylated
      in human DIPGs, resulting in the increased expression of NG2. Treatment with 5
      Azacytidine, a methyltransferase inhibitor, results in NG2 downregulation in DIPG
      primary tumor cells in vitro. NG2 expression is altered (symmetric segregation)
      in mitotic human DIPG and mouse tumor cells. These mitotic cells co-express
      oligodendrocyte (Olig2) and astrocyte (glial fibrillary acidic protein, GFAP)
      markers, indicating lack of terminal differentiation. NG2 knockdown retards
      cellular migration in vitro, while NG2 expressing neurospheres are highly
      tumorigenic in vivo, resulting in rapid growth of pontine tumors. NG2 expression
      is targetable in vivo using miR129-2 indicating a potential avenue for
      therapeutic interventions. This data implicates NG2 as a molecule of interest in
      DIPGs especially those with H3.3 mutation. 

PMID- 25987130
TI  - Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes
      gliomagenesis.
AB  - The most abundant populations of non-neoplastic cells in the glioblastoma (GBM)
      microenvironment are resident microglia, macrophages and infiltrating monocytes
      from the blood circulation. The mechanisms by which monocytes infiltrate into
      GBM, their fate following infiltration, and their role in GBM growth are not
      known. Here we tested the hypothesis that loss of the fractalkine receptor CX3CR1
      in microglia and monocytes would affect gliomagenesis. Deletion of Cx3cr1 from
      the microenvironment resulted in increased tumor incidence and shorter survival
      times in glioma-bearing mice. Loss of Cx3cr1 did not affect accumulation of
      microglia/macrophages in peri-tumoral areas, but instead indirectly promoted the
      trafficking of CD11b+CD45hiCX3CR1lowLy-6ChiLy-6G-F4/80-/low circulating
      inflammatory monocytes into the CNS, resulting in their increased accumulation in
      the perivascular area. Cx3cr1-deficient microglia/macrophages and monocytes
      demonstrated upregulation of IL1beta expression that was inversely proportional
      to Cx3cr1 gene dosage. The Proneural subgroup of the TCGA GBM patient dataset
      with high IL1beta expression showed shorter survival compared to patients with
      low IL1beta. IL1beta promoted tumor growth and increased the cancer stem cell
      phenotype in murine and human Proneural glioma stem cells (GSCs). IL1beta
      activated the p38 MAPK signaling pathway and expression of monocyte
      chemoattractant protein (MCP-1/CCL2) by tumor cells. Loss of Cx3cr1 in microglia
      in a monocyte-free environment had no impact on tumor growth and did not alter
      microglial migration. These data suggest that enhancing signaling to CX3CR1 or
      inhibiting IL1beta signaling in intra-tumoral macrophages can be considered as
      potential strategies to decrease the tumor-promoting effects of monocytes in
      Proneural GBM. 

PMID- 25987131
TI  - Integrated genomic analyses identify frequent gene fusion events and VHL
      inactivation in gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. We sequenced nine exomes and transcriptomes, and two
      genomes of GISTs for integrated analyses. We detected 306 somatic variants in
      nine GISTs and recurrent protein-altering mutations in 29 genes. Transcriptome
      sequencing revealed 328 gene fusions, and the most frequently involved fusion
      events were associated with IGF2 fused to several partner genes including CCND1,
      FUS, and LASP1. We additionally identified three recurrent read-through fusion
      transcripts: POLA2-CDC42EP2, C8orf42-FBXO25, and STX16-NPEPL1. Notably, we found
      intragenic deletions in one of three exons of the VHL gene and increased mRNAs of
      VEGF, PDGF-beta, and IGF-1/2 in 56% of GISTs, suggesting a mechanistic link
      between VHL inactivation and overexpression of hypoxia-inducible factor target
      genes in the absence of hypoxia. We also identified copy number gain and
      increased mRNA expression of AMACR, CRIM1, SKP2, and CACNA1E. Mapping of copy
      number and gene expression results to the KEGG pathways revealed activation of
      the JAK-STAT pathway in small intestinal GISTs and the MAPK pathway in wild-type
      GISTs. These observations will allow us to determine the genetic basis of GISTs
      and will facilitate further investigation to develop new therapeutic options.

PMID- 25987133
TI  - Advances in Anthrax Detection: Overview of Bioprobes and Biosensors.
AB  - Anthrax is an infectious disease caused by Bacillus anthracis. Although anthrax
      commonly affects domestic and wild animals, it causes a rare but lethal infection
      in humans. A variety of techniques have been introduced and evaluated to detect
      anthrax using cultures, polymerase chain reaction, and immunoassays to address
      the potential threat of anthrax being used as a bioweapon. The high-potential
      harm of anthrax in bioterrorism requires sensitive and specific detection systems
      that are rapid, field-ready, and real-time monitoring. Here, we provide a
      systematic overview of anthrax detection probes with their potential applications
      in various ultra-sensitive diagnostic systems. 

PMID- 25987134
TI  - A NaBH4 Coupled Ninhydrin-Based Assay for the Quantification of Protein/Enzymes
      During the Enzymatic Hydrolysis of Pretreated Lignocellulosic Biomass.
AB  - Accurate protein quantification is necessary in many of the steps during the
      enzymatic hydrolysis of pretreated lignocellulosic biomass, from the fundamental
      determination of enzyme kinetics to techno-economic assessments, such as the use
      of enzyme recycling strategies, evaluation of enzyme costs, and the optimization
      of various process steps. In the work described here, a modified, more rapid
      ninhydrin-based protein quantification assay was developed to better quantify
      enzyme levels in the presence of lignocellulosic biomass derived compounds. The
      addition of sodium borohydride followed by acid hydrolysis at 130  degrees C
      greatly reduced interference from monosaccharides and oligosaccharides and
      decreased the assay time 6-fold. The modified ninhydrin assay was shown to be
      more accurate as compared to various traditional colorimetric protein assays when
      commercial cellulase enzyme mixtures were quantified under typical pretreated
      lignocellulosic biomass enzymatic hydrolysis conditions. The relatively short
      assay time and microplate-reading capability of the modified assay indicated that
      the method could likely be used for high-throughput protein determination.

PMID- 25987135
TI  - Process Integration for the Disruption of Candida guilliermondii Cultivated in
      Rice Straw Hydrolysate and Recovery of Glucose-6-Phosphate Dehydrogenase by
      Aqueous Two-Phase Systems.
AB  - Remaining cells of Candida guilliermondii cultivated in hemicellulose-based
      fermentation medium were used as intracellular protein source. Recovery of
      glucose-6-phosphate dehydrogenase (G6PD) was attained in conventional aqueous two
      phase systems (ATPS) was compared with integrated process involving mechanical
      disruption of cells followed by ATPS. Influences of polyethylene glycol molar
      mass (M PEG) and tie line lengths (TLL) on purification factor (PF), yields in
      top (Y T ) and bottom (Y B ) phases and partition coefficient (K) were evaluated.
      First scheme resulted in 65.9 % enzyme yield and PF of 2.16 in salt-enriched
      phase with clarified homogenate (M PEG 1500 g mol(-1), TLL 40 %); Y B of 75.2 %
      and PF B of 2.9 with unclarified homogenate (M PEG 1000 g mol(-1), TLL 35 %). The
      highest PF value of integrated process was 2.26 in bottom phase (M PEG 1500 g
      mol(-1), TLL 40 %). In order to optimize this response, a quadratic model was
      predicted for the response PFB for process integration. Maximum response achieved
      was PFB = 3.3 (M PEG 1500 g mol(-1), TLL 40 %). Enzyme characterization showed
      G6P Michaelis-Menten constant (K M ) equal 0.07-0.05, NADP(+) K M 0.02-1.98 and
      optimum temperature 70  degrees C, before and after recovery. Overall, our data
      confirmed feasibility of disruption/extraction integration for single-step
      purification of intracellular proteins from remaining yeast cells.

PMID- 25987136
TI  - Modelling Growth and Bacteriocin Production by Lactobacillus plantarum BC-25 in
      Response to Temperature and pH in Batch Fermentation.
AB  - The use of bacteriocin-producing probiotics to improve food fermentation
      processes seems promising. However, lack of fundamental information about their
      functionality and specific characteristics may hinder their industrial use.
      Predictive microbiology may help to solve this problem by simulating the kinetics
      of bacteriocin-producing strains and optimising the cell growth and production of
      beneficial metabolites. In this study, a combined model was developed which could
      estimate, from a given initial condition of temperature and pH, the growth and
      bacteriocin production of Lactobacillus plantarum BC-25 in MRS broth. A logistic
      model was used to model the growth of cells, and the Luedeking-Piret model was
      used to simulate the biomass and bacteriocin production. The parameters generated
      from these primary models were used in a response surface model to describe the
      combined influence on cell growth, biomass and bacteriocin production. Both the
      temperature and pH influenced cell and bacteriocin production significantly. The
      optimal temperature and pH for cell growth is 35  degrees C and 6.8, and the
      optimal bacteriocin production condition is a range dependent on two growth
      associated constants (YA/X and K), where temperature is from 27 to 34  degrees C,
      and pH is 6.35 to 6.65. The developed model is consistent with similar studies
      and could be a useful tool to control and increase the production of lactic acid
      bacteria in bioreactors.

PMID- 25987137
TI  - Rural health inequities: data and decisions.

PMID- 25987138
TI  - Keeping watch on women's cancers.

PMID- 25987139
TI  - UK immigrant health surcharge: unfair and short-sighted.

PMID- 25987140
TI  - Global health security now.

PMID- 25987142
TI  - Nepal earthquake exposes gaps in disaster preparedness.

PMID- 25987145
TI  - Anatomy: back in the public spotlight.

PMID- 25987146
TI  - Rethinking personalised medicine.

PMID- 25987147
TI  - John Arras.

PMID- 25987148
TI  - Research investment disparities in England.

PMID- 25987149
TI  - End late registration of fact-of-death in England and Wales.

PMID- 25987150
TI  - Burnout in NHS staff.

PMID- 25987151
TI  - Mental health: needs go beyond RCTs.

PMID- 25987152
TI  - Mental health: needs go beyond RCTs.

PMID- 25987153
TI  - A public health approach to hypertension.

PMID- 25987154
TI  - A public health approach to hypertension.

PMID- 25987155
TI  - A public health approach to hypertension.

PMID- 25987156
TI  - Department of Error.

PMID- 25987158
TI  - A retrospective and prospective analysis of the west African Ebola virus disease
      epidemic: robust national health systems at the foundation and an empowered WHO
      at the apex.
AB  - The Ebola virus disease outbreak in west Africa is pivotal for the worldwide
      health system. Just as the depth of the crisis ultimately spurred an
      unprecedented response, the failures of leadership suggest the need for
      innovative reforms. Such reforms would transform the existing worldwide health
      system architecture into a purposeful, organised system with an empowered, highly
      capable WHO at its apex and enduring, equitable national health systems at its
      foundation. It would be designed not only to provide security against epidemic
      threats, but also to meet everyday health needs, thus realising the right to
      health. This retrospective and prospective analysis offers a template for these
      reforms, responding to the profound harms posed by fragile national health
      systems, delays in the international response, deficient resource mobilisation,
      ill defined responsibilities, and insufficient coordination. The scope of the
      reforms should address failures in the Ebola response, and entrenched weaknesses
      that enabled the epidemic to reach its heights. 

PMID- 25987159
TI  - What is a resilient health system? Lessons from Ebola.

PMID- 25987157
TI  - Global health security: the wider lessons from the west African Ebola virus
      disease epidemic.
AB  - The Ebola virus disease outbreak in West Africa was unprecedented in both its
      scale and impact. Out of this human calamity has come renewed attention to global
      health security--its definition, meaning, and the practical implications for
      programmes and policy. For example, how does a government begin to strengthen its
      core public health capacities, as demanded by the International Health
      Regulations? What counts as a global health security concern? In the context of
      the governance of global health, including WHO reform, it will be important to
      distil lessons learned from the Ebola outbreak. The Lancet invited a group of
      respected global health practitioners to reflect on these lessons, to explore the
      idea of global health security, and to offer suggestions for next steps. Their
      contributions describe some of the major threats to individual and collective
      human health, as well as the values and recommendations that should be considered
      to counteract such threats in the future. Many different perspectives are
      proposed. Their common goal is a more sustainable and resilient society for human
      health and wellbeing.

PMID- 25987160
TI  - Pinpointing clinical diagnosis through whole exome sequencing to direct patient
      care: a case of Senior-Loken syndrome.

PMID- 25987162
TI  - Colorectal cancer among persons with HIV: protocol for a systematic review and
      meta-analysis.
AB  - BACKGROUND: As persons with HIV live longer, data regarding the epidemiology of
      colorectal cancer are required to optimize the long-term management of these
      patients. The purpose of this systematic review and meta-analysis is to
      synthesize evidence regarding the incidence of colorectal cancer in persons with
      HIV. METHODS/DESIGN: Our primary outcome is the standardized incidence ratio of
      colorectal cancer among persons with HIV relative to rates in persons not living
      with HIV. Our secondary objectives are to summarize the evidence for differences
      with respect to stage at diagnosis, site of disease, and mortality due to
      colorectal cancer. We will search electronic bibliographic databases from their
      inception date, as well as conference proceedings and reference lists of included
      articles. Two investigators will independently screen citations and full-text
      articles, conduct data abstraction, and appraise study quality. We will examine
      clinical, methodological, and statistical heterogeneity among studies prior to
      conducting meta-analysis. Random effects meta-analysis methods will be employed
      to estimate standardized incidence ratios. These data will inform the development
      of guidelines for colorectal cancer screening in persons with HIV. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42014013449.

PMID- 25987163
TI  - Whole blood human neutrophil trafficking in a microfluidic model of infection and
      inflammation.
AB  - Appropriate inflammatory responses to wounds and infections require adequate
      numbers of neutrophils arriving at injury sites. Both insufficient and excessive
      neutrophil recruitment can be detrimental, favouring systemic spread of microbes
      or triggering severe tissue damage. Despite its importance in health and disease,
      the trafficking of neutrophils through tissues remains difficult to control and
      the mechanisms regulating it are insufficiently understood. These mechanisms are
      also complex and difficult to isolate using traditional in vivo models. Here we
      designed a microfluidic model of tissue infection/inflammation, in which human
      neutrophils emerge from a droplet-size samples of whole blood and display bi
      directional traffic between this and micro-chambers containing chemoattractant
      and microbe-like particles. Two geometrical barriers restrict the entrance of red
      blood cells from the blood to the micro-chambers and simulate the mechanical
      function of the endothelial barrier separating the cells in blood from cells in
      tissues. We found that in the presence of chemoattractant, the number of
      neutrophils departing the chambers by retrotaxis is in dynamic equilibrium with
      the neutrophils recruited by chemotaxis. We also found that in the presence of
      microbe-like particles, the number of neutrophils trapped in the chambers is
      proportional to the number of particles. Together, the dynamic equilibrium
      between migration, reversed-migration and trapping processes determine the
      optimal number of neutrophils at a site. These neutrophils are continuously
      refreshed and responsive to the number of microbes. Further studies using this
      infection-inflammation-on-a-chip-model could help study the processes of
      inflammation resolution. The new in vitro experimental tools may also eventually
      help testing new therapeutic strategies to limit neutrophil accumulation in
      tissues during chronic inflammation, without increasing the risk for infections. 

PMID- 25987164
TI  - Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology.
AB  - Vitamin D and FGF23 play a major role in calcium/phosphate balance. Vitamin D may
      control bone resorption but the potential role of FGF23 has never been evaluated.
      The objective of this study was therefore to compare the effects of vitamin D and
      FGF23 on osteoclast differentiation and activity in human monocyte-derived
      osteoclasts. Human monocytes, purified from blood of healthy donors, were
      incubated with M-CSF and RANKL to obtain mature multinucleated osteoclasts (MNC).
      Experiments were carried out to assess the effects of FGF23 as compared to native
      vitamin D (25-D) and active vitamin D (1,25-D) on osteoclast differentiation and
      on bone-resorbing osteoclast activity. Additional experiments with the pan
      fibroblast growth factor receptor inhibitor (FGFR-i) were performed.
      Phosphorylation Akt and Erk pathways were analyzed by Western blot analyses. Both
      1,25-D and FGF23, to a lesser extent, significantly inhibited osteoclastogenesis
      at early stages; when adding FGFR-i, osteoclast formation was restored.
      Biochemical experiments showed an activation of the Akt and Erk pathways under
      FGF23 treatment. In contrast, in terms of activity, 1,25-D had no effect on
      resorption, whereas FGF23 slightly but significantly increased bone resorption;
      25-D had no effects on either differentiation or on activity. These data show
      that 1,25-D inhibits osteoclastogenesis without regulating osteoclast-mediated
      bone resorption activity; FGF23 has biphasic effects on osteoclast physiology,
      inhibiting osteoclast formation while stimulating slightly osteoclast activity.
      These results may be of importance and taken into account in chronic kidney
      disease when therapies modulating FGF23 are available. 

PMID- 25987165
TI  - Hydrolysis enhances bioavailability of proanthocyanidin-derived metabolites and
      improves beta-cell function in glucose intolerant rats.
AB  - Proanthocyanidins (PAC) are a highly consumed class of flavonoids and their
      consumption has been linked to beneficial effects in type 2 diabetes. However,
      limited gastrointestinal absorption occurs due to the polymeric structure of PAC.
      We hypothesized that hydrolysis of the PAC polymer would increase
      bioavailability, thus leading to enhanced beneficial effects on glucose
      homeostasis and pancreatic beta-cell function. PAC-rich pea seed coats (PSC) were
      supplemented to a high-fat diet (HFD) either in native (PAC) or hydrolyzed (HPAC)
      form fed to rats for 4 weeks. HFD or low-fat diet groups were controls. PAC
      derived compounds were characterized in both PSC and serum. Glucose and insulin
      tolerance tests were conducted. Pancreatic alpha-cell and beta-cell areas and
      glucose-stimulated insulin secretion (GSIS) from isolated islets were measured.
      Increased PAC-derived metabolites were detected in the serum of HPAC-fed rats
      compared to PAC-fed rats, suggesting hydrolysis of PSC-enhanced PAC
      bioavailability. This was associated with ~18% less (P<.05) weight gain compared
      to HFD without affecting food intake, as well as improvement in glucose disposal
      in vivo. There was a 2-fold decrease of alpha/beta-cell area ratio and a 2.5-fold
      increase in GSIS from isolated islets of HPAC-fed rats. These results demonstrate
      that hydrolysis of PSC-derived PAC increased the bioavailability of PAC-derived
      products, which is critical for enhancing beneficial effects on glucose
      homeostasis and pancreatic beta-cell function. 

PMID- 25987167
TI  - Lysosomal storage disorders. Preface.

PMID- 25987166
TI  - Predicting Infections After Total Joint Arthroplasty Using a Prescription Based
      Comorbidity Measure.
AB  - This study evaluated the association and predictive ability of co-morbidities
      measured by RxRisk-V, Elixhauser and Charlson measures and post-total hip (THA)
      and total knee arthroplasties (TKA) infection. THAs and TKAs (2001-2012) were
      identified using the Australian Department of Veterans' Affairs data. Infections
      within 90 days post-surgery were the study endpoint. Co-morbidities were
      identified using pharmacy (RxRisk-V) and hospitalization history (Elixhauser,
      Charlson). Of the 11,848 THAs, 3.1% (N = 364) had infections and out of 18,972
      TKAs 3.4% (N = 648). Comorbidity burden and specific conditions were associated
      with infection likelihood. RxRisk-V performed better than other measures, but
      none had high predictive ability and differences were small. The best performing
      infection prediction models resulted when a combination of conditions identified
      by all measures was used.

PMID- 25987168
TI  - Bridging the age spectrum of neurodegenerative storage diseases.
AB  - For over a century, researchers have observed similar neurodegenerative hallmarks
      in brains of people affected by rare early-onset lysosomal storage diseases and
      late-onset neurodegenerative diseases such as Alzheimer's and Parkinson's
      disease. Increasing evidence suggests these apparently disparate diseases share a
      common underlying feature, namely, a dysfunctional clearance of cellular cargo
      through the secretory-endosomal-autophagic-lysosomal-exocytic (SEALE) network. By
      providing examples of rare and common neurodegenerative diseases known to have
      pathologically altered cargo flux through the SEALE network, we explore the
      unifying hypothesis that impaired catabolism or exocytosis of SEALE cargo, places
      a burden of stress on neurons that initiates pathogenesis. We also describe how a
      growing understanding of genetic, epigenetic and age-related modifications of the
      SEALE network, has inspired a number of novel disease-modifying therapeutic
      approaches aimed at alleviating SEALE storage and providing therapeutic benefit
      to people affected by these devastating diseases across the age spectrum. 

PMID- 25987169
TI  - Epidemiology and diagnosis of lysosomal storage disorders; challenges of
      screening.
AB  - The lysosomal storage disorders (LSDs) are a group of genetic disorders resulting
      from defective lysosomal metabolism and subsequent accumulation of substrates.
      Patients present with a large phenotypic spectrum of disease manifestations that
      are generally not specific for LSDs, leading to considerable diagnostic delay and
      missed cases. Introduction of new disease modifying therapies for LSDs has made
      early diagnosis a priority. Increased awareness, but particularly the
      introduction of screening programs allow for early diagnosis and timely
      initiation of treatment. This review will provide insight into the epidemiology
      and diagnostic process for LSDs. In addition, challenges for carrier screening,
      high-risk screening and newborn population screening for LSDs are discussed. 

PMID- 25987170
TI  - Neuronopathic lysosomal storage disorders: Approaches to treat the central
      nervous system.
AB  - Pharmacological research has always focused on developing new therapeutic
      strategies capable of modifying a disease's natural history and improving
      patients' quality of life. Despite recent advances within the fields of medicine
      and biology, some diseases still represent a major challenge for successful
      therapy. Neuronopathic lysosomal storage disorders, in particular, have high
      rates of morbidity and mortality and a devastating socio-economic effect. Many of
      the available therapies, such as enzyme replacement therapy, can reverse the
      natural history of the disease in peripheral organs but, unfortunately, are still
      unable to reach the central nervous system effectively because they cannot cross
      the blood-brain barrier that surrounds and protects the brain. Moreover, many
      lysosomal storage disorders are characterized by a number of blood-brain barrier
      dysfunctions, which may further contribute to disease neuropathology and
      accelerate neuronal cell death. These issues, and their context in the
      development of new therapeutic strategies, will be discussed in detail in this
      chapter. 

PMID- 25987171
TI  - Non-neuronopathic lysosomal storage disorders: Disease spectrum and treatments.
AB  - Distinctive facial features, hepatosplenomegaly or cardiomyopathy with or without
      associated skeletal dysplasia are clinical manifestations that may be suggestive
      of an underlying lysosomal storage disorder (LSD), However, these features may
      not be evident in certain subtypes associated primarily with central nervous
      system involvement. Age at onset can be broad, ranging from infancy to adulthood.
      Diagnosis may be delayed, as manifestations may be slow to evolve (taking months
      to years), particularly in those with later (adult-)onset, and in isolated cases
      (i.e., those without a prior family history). Diagnosis of individual subtypes
      can be confirmed using a combination of biochemical and molecular assays. In a
      few LSDs, treatment with hematopoietic stem cell transplantation, enzyme
      replacement or substrate reduction therapy is available. Symptomatic and
      palliative measure may enhance quality of life for both treatable and currently
      untreatable cases. Genetic counseling is important, so patients and their
      families can be informed of reproductive risks, disease prognosis and therapeutic
      options. Investigations of underlying disease mechanisms are enhancing knowledge
      about rare diseases, but also other more common medical conditions, on account of
      potential convergent disease pathways. 

PMID- 25987172
TI  - The role of antibodies in enzyme treatments and therapeutic strategies.
AB  - Substitution of the defective lysosomal enzyme in lysosomal storage disorders
      (LSDs) often elicits antibody formation towards the infused protein. Aside from
      Gaucher disease, antibodies often lead to infusion associated reactions and a
      reduced biochemical response. In Pompe disease, antibody titer is predictive of
      clinical outcome, but this is less apparent in other LSDs and warrants further
      study. Few laboratories are capable of enzyme-antibody determination: often
      physicians need to rely on the enzyme manufacturer for analysis. Currently,
      laboratories employ different antibody assays which hamper comparisons between
      cohorts or treatment regimens. Assay standardisation, including measurement of
      antibody-related enzyme inhibition, is therefore urgently needed. Successful
      immunomodulation has been reported in Pompe and in Gaucher disease, with variable
      success. Immunomodulation regimens that contain temporary depletion of B-cells
      (anti-CD20) are most used. Bone marrow transplantation in MPS-I results in
      disappearance of antibodies. No other clinical studies have been conducted in
      humans with immunomodulation in other LSDs. 

PMID- 25987173
TI  - Fabry disease and the heart.
AB  - Fabry disease is induced by a mutation in the alpha-galactosidase A gene, causing
      a deficiency of the enzyme alpha-galactosidase A. (1) The enzyme defect leads to
      progressive intracellular accumulation of globotriaosylceramide in lysosomes of
      various tissues and organs, including heart, kidney and nerve system. Cardiac
      involvement is common and is presenting as concentric left ventricular
      hypertrophy. Myocardial replacement fibrosis is a typical feature of more
      advanced stages of Fabry cardiomyopathy, first limited to the mid-myocardial
      layers of the basal postero-lateral wall, then spreading to transmural fibrosis.
      Since 2001, enzyme replacement therapy is available. If therapy is started early,
      before myocardial fibrosis has developed, a long-term improvement of myocardial
      morphology, function and exercise capacity can be achieved. In end-stage
      cardiomyopathy enzyme replacement therapy might prevent further progression of
      the disease. This review provides an overview of Fabry disease, with a focus on
      cardiac involvement with its characteristic features, clinical presentation and
      possible treatment. 

PMID- 25987174
TI  - The attenuated/late onset lysosomal storage disorders: Therapeutic goals and
      indications for enzyme replacement treatment in Gaucher and Fabry disease.
AB  - Enzyme replacement therapies have been developed and authorized for commercial
      use for six different lysosomal storage disorders. For Gaucher disease, Fabry
      disease and mucopolysaccharidosis type 1, disease-specific treatments have been
      available for more than a decade. Although long term follow-up data are still
      sparse, therapeutic goals for patients with Gaucher disease and Fabry disease
      have been formulated and published for both adults and children. Without
      adaptation or modification, these goals are often applied in clinical research
      and in routine patient care across the entire phenotypic spectrum of disease,
      although in practice, patients commonly manifest high variability in clinical
      presentation and course of the illness. In this context, establishing goals for
      the follow-up and treatment of late onset/attenuated phenotypes is particularly
      challenging. In this chapter, we review current therapeutic goals for Gaucher
      disease and Fabry disease and discuss approaches for those with attenuated
      disease manifestations. 

PMID- 25987175
TI  - The clinical spectrum and pathophysiology of skeletal complications in lysosomal
      storage disorders.
AB  - Lysosomal storage disorders affect multiple organs including the skeleton.
      Disorders with prominent skeletal symptoms are type 1 and 3 Gaucher disease, the
      mucopolysaccharidoses, the glycoproteinoses and pycnodysostosis. Clinical
      manifestations range from asymptomatic radiographical evidence of bone pathology
      to overt bone crises (Gaucher), short stature with typical imaging features known
      as dysostosis multiplex (MPS), with spine and joint deformities
      (mucopolysaccharidoses, mucolipidosis), or osteopetrosis with pathological
      fractures (pynodysostosis). The pathophysiology of skeletal disease is only
      partially understood and involves direct substrate storage, inflammation and
      other complex alterations of cartilage and bone metabolism. Current treatments
      are enzyme replacement therapy, substrate reduction therapy and hematopoietic
      stem cell transplantation. However, effects of these interventions on skeletal
      disease manifestations are less well established and outcomes are highly
      dependent on disease burden at treatment initiation. It is now clear that
      adjunctive treatments that target skeletal disease are needed and should be part
      of future research agenda. 

PMID- 25987176
TI  - Types A and B Niemann-Pick disease.
AB  - Two distinct metabolic abnormalities are encompassed under the eponym Niemann
      Pick disease (NPD). The first is due to the deficient activity of the enzyme acid
      sphingomyelinase (ASM). Patients with ASM deficiency are classified as having
      types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit
      hepatosplenomegaly in infancy and profound central nervous system involvement.
      They rarely survive beyond two years of age. Type B patients also have
      hepatosplenomegaly and pathologic alterations of their lungs, but there are
      usually no central nervous system signs. The age of onset and rate of disease
      progression varies greatly among type B patients, and they frequently live into
      adulthood. Recently, patients with phenotypes intermediate between types A and B
      NPD also have been identified. These individuals represent the expected continuum
      caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the
      second NPD category are designated as having types C and D NPD. These patients
      may have mild hepatosplenomegaly, but the central nervous system is profoundly
      affected. Impaired intracellular trafficking of cholesterol causes types C and D
      NPD, and two distinct gene defects have been found. In this chapter only types A
      and B NPD will be discussed. 

PMID- 25987177
TI  - The emergence of Parkinson disease among patients with Gaucher disease.
AB  - In the last decade, several lines of evidence have been presented that document
      the clinical manifestations, genetic associations, and sub-cellular mechanisms of
      the inter-relatedness of beta-glucocerebrosidase mutations and the emergence of
      Parkinson disease among carriers and patients with Gaucher disease. This review
      is an attempt to apprise the reader of the recent literature with the caveat that
      this is an area of intensive exploration that is constantly being updated because
      of the immediate clinical ramifications but also because of the impact on our
      understanding of Parkinson disease, and finally because of the unexpected inter
      reactions between these entities on the molecular level. It has been an
      unexpected happenstance that it has been discovered that a rare monogenetic
      disease has an interface at many points with a neurological disorder of the
      elderly that has both familial and sporadic forms: to date there is no cure for
      either of these disorders. 

PMID- 25987178
TI  - Metachromatic leukodystrophy: Disease spectrum and approaches for treatment.
AB  - Metachromatic leukodystrophy is an inherited lysosomal disorder caused by
      recessive mutations in ARSA encoding arylsulfatase A. Low activity of
      arylsulfatase A results in the accumulation of sulfatides in the central and
      peripheral nervous system leading to demyelination. The disease is classified in
      a late-infantile, juvenile and adult onset type based on the age of onset, all
      characterized by a variety of neurological symptoms, which eventually lead to
      death if untreated. There is no curative treatment for all types and stages. This
      review discusses diagnostic process and efficacy of current and possible future
      therapies such as hematopoietic stem cell transplantation, enzyme replacement
      therapy and gene therapy. A systematic evaluation regarding the efficacy of
      hematopoietic stem cell transplantation and a longer follow up period for gene
      therapy are needed to come to a general conclusion and improve treatment options
      for metachromatic leukodystrophy. 

PMID- 25987179
TI  - Innovative treatments for lysosomal diseases.
AB  - Striking therapeutic advances for lysosomal diseases have harnessed the biology
      of this organelle and illustrate its central role in the dynamic economy of the
      cell. Further Innovation will require improved protein-targetting or realization
      of therapeutic gene- and cell transfer stratagems. Rescuing function before
      irreversible injury, mandates a deep knowledge of clinical behaviour as well as
      molecular pathology - and frequently requires an understanding of neuropathology.
      Whether addressing primary causes, or rebalancing the effects of disordered cell
      function, true therapeutic innovation depends on continuing scientific
      exploration of the lysosome. Genuine partnerships between biotech and the
      patients affected by this extraordinary family of disorders continue to drive
      productive pharmaceutical discovery.

PMID- 25987180
TI  - Structural underpinnings of functional plasticity in rodent visual cortex.
AB  - Functional plasticity in rodent visual cortex has been intensively studied since
      the pioneering experiments of Hubel and Wiesel in the sixties. Nevertheless, the
      structural modifications underlying this phenomenon remain elusive. In this
      article, we will review recent data focused on the dynamic of excitatory and
      inhibitory synapses and their structural changes linked to functional
      modifications. We also review novel evidence on structural remodeling that
      promote functional plasticity and on the role of cytoskeleton modifications in
      experience-dependent plasticity of rodent visual cortex. 

PMID- 25987181
TI  - Brain plasticity and recovery in preclinical models of stroke.
AB  - Post-stroke recovery relies on neurobiological changes that modify the
      organization and function of the brain under pathophysiological conditions. The
      changes can be adaptive (i.e. restoration of function) or maladaptive (i.e.
      worsening of function). Preclinical models of stroke exhibit adaptive plasticity
      that leads to a "spontaneous recov- ery" of functions. This recovery can be
      modulated through external factors, such as rehabilitation, pharmacology or other
      adjuvant strategies. Nevertheless, current interventions only result in a limited
      improvement of deficits and there is also potential for maladaptation. Hence, a
      better understanding of the mechanisms underlying recovery is essential for the
      design of more efficient and targeted treatment strategies. Here, we review the
      main features of adaptive plasticity that are thought to underlie the spontaneous
      and induced recovery of function in animal models of stroke. Within this context,
      therapeutic interventions, used in isolation or synergistically to modulate
      recovery, are discussed. It is hoped that a focus on neurobiological principles
      and their manipulation will enhance interven- tional strategies to maximize
      therapeutic benefit. To ensure translation of these interventions into a clinical
      setting, a close interaction between basic and applied research is required. 

PMID- 25987182
TI  - Neurophysiological markers of plastic brain reorganization following central and
      peripheral lesions.
AB  - There is increasing evidence supporting the concept that adult brain has the
      remarkable ability to plastically reorganize itself. Brain plasticity involves
      distinct functional and structural components and plays a crucial role in
      reorganizing central nervous system's networks after central and peripheral
      lesions in order to partly or totally restore lost and/or compromised functions.
      This plastic rearrangement occurs in fact not only after a central nervous system
      injury but also following a peripheral lesion. Interestingly, the existence of a
      certain type of maladaptive plasticity was clearly recognized in the last decade,
      which gives reason for example to poor out- come performances or aberrant
      phenomena. In this review we analyze stroke and amputees studies, as illustrative
      conditions of central and peripheral nervous system damage, and discuss the
      adaptive as well maladaptive plastic brain changes following these lesions. The
      emerging possibility, through neuro-imaging and neurophysiological advanced
      techniques, to clarify some crucial issues underlying brain plasticity will give
      the chance to modulate these mechanisms in a highly personalized therapy. This
      approach may have a tremendous impact in a variety of neuropsychiatric disorders
      opening a new era of restorative medicine. 

PMID- 25987183
TI  - Cortical plasticity in patients with Parkinson's disease a window for therapeutic
      non-invasive neuromodulation.
AB  - Several evidences in animal models have consistently an alteration of cortico
      striatal plasticity, which is related to the degeneration of the substantia
      nigra. An alteration of plasticity have also been reported in humans by recording
      evoked field potentials in the substantia nigra pars reticulata of PD patients
      undergoing subthalamic nucleus (STN) stimulation where high-frequency (HF) in the
      OFF state did not induce a lasting change in field potential amplitude in the
      substantia nigra. In addition protocols of non-invasive brain stimulation, such
      as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be
      used to investigate cortical plasticity of the human primary motor cortex.
      Despite data reported in literature are apparently controversial with some
      studies showing a reduced or increased or even normal LTP and LTD like
      plasticity, recent evidences suggest the hypothesis that these different pat-
      terns of cortical plasticity likely depend on the stage of the disease and on the
      concomitant administration of L-DOPA. The current review will provide an up-to
      date of these issues on cortical plasticity in PD discussing the clinical
      implications in rehabilitation. In addition in the last section we will review
      the state of art of non invasive neuro- modulation as adjuvant treatment in the
      advanced stage of the disease. 

PMID- 25987184
TI  - NIBS-driven brain plasticity.
AB  - Through plasticity the brain is able to change its function and to rearrange
      following injury or environmental changes. In recent years, it was shown that non
      invasive brain stimulation (NIBS) techniques, especially transcra- nial magnetic
      stimulation (TMS) and transcranial direct current stimulation (tDCS) can
      contribute to understand how these plastic changes occur. Additionally, the
      literature suggests that TMS and tDCS may be used as interven- tional strategies
      to improve neurorehabilitation efforts and arguably recovery of motor function
      after brain lesions. This review focuses on the use of NIBS in experimental
      protocols for evaluation and modulation of brain plastic- ity, the factors
      contributing to the inter-individual variability of response, proposed mechanisms
      and difficulties in translating findings from small proof of principle studies
      through the pipeline to clinical practice. 

PMID- 25987185
TI  - Clinical evidences of brain plasticity in stroke patients.
AB  - Emerging findings deriving from neuromodulation and neuroradiology are providing
      us new insights about plas- ticity and functional reorganization of the brain
      after stroke, but the direct clinical assessment of motor function should still
      be considered an indispensable tool for the evaluation of the effects of
      plasticity in stroke patients. Recovery of motor function can be spontaneous or
      guided by training. Substantial functional recovery can occur spontaneously
      especially in the first month post-stroke. Instead, the guided recovery may take
      more time and may rely on a number of rehabilitation techniques which proved to
      be capable of stimulating cerebral plasticity. Even the time course of these
      processes is a decisive element. First, it is important to correlate the trends
      of plasticity after stroke, from the enhancement of earlier periods to the later
      stages, to the behavioral changes observed. Furthermore, it is crucial to
      distinguish recovery of function occurring through improvement of motor deficit
      from compensatory mechanisms, distinction that has also an effect on timing of
      recovery. Another relevant question is the maintenance over time of the
      improvements reached with the treatment, feature on which various clinical
      studies have been conducted in acute and chronic stroke patients. Further studies
      are needed to allow us to get a more precise definition of the potentiality of
      functional recovery and of the mechanisms underlying the recovery depending on
      its levels and timing. Understanding the mechanisms, the effects and the limits
      of neural plasticity may eventually help enhancing the recovery process in stroke
      patients, significantly improving the quality of life of these patients. Then, a
      greater attention towards the clinical implica- tions of the changes related to
      plasticity can be a crucial element to further improve the therapeutic options
      used in neurorehabilitation. 

PMID- 25987186
TI  - Albumin anchored docetaxel lipid nanoemulsion for improved targeting efficiency -
      preparation, characterization, cytotoxic, antitumor and in vivo imaging studies.
AB  - The aim was to develop albumin anchored docetaxel lipid nanoemulsion (ALNE) for
      improving tumor targeted delivery. The O/W lipid nanoemulsion, LNEs were prepared
      by homogenization and ultrasonication processes. The size of globules and zeta
      potential were measured by Malvern Zetasizer. Albumin was coupled to stearylamine
      containing lipid nanoemulsion (SALNE) globules using water soluble EDC reaction.
      The drug content and entrapment efficiencies for the LNEs were determined by the
      high-performance liquid chromatography. The in vitro cytotoxic studies of the
      delivery systems were performed on MCF-7 and Hela cells. The IC 50 values of ALNE
      on both the cell lines were statistically significant. The in vivo antitumor
      activity was tested on solid tumors induced in C57BL/6 mice. This study revealed
      that the percentage tumor inhibition for the groups treated with DLNE, SALNE and
      ALNE when compared with untreated control was found to be 55.62 +/- 5.41%, 54.27
      +/- 4.85% and 80.01 +/- 2.74%, respectively. Furthermore, in vivo distribution
      studies were carried out in breast cancer MDA-MB231 xenografted Balb/c mice. The
      LNEs were loaded with fluorescent DiD oil and the distribution in different
      organs after 6 h was tracked using Caliper life sciences in vivo imaging system.
      The studies revealed that ALNE was superior in tumor targeting activity when
      compared with DLNE and SALNE by 3.04 and 2.26 folds, respectively. The average
      radiance values of ALNE on the tumor tissue were statistically significant when
      compared with DLNE, SALNE at p < 0.01. In addition, this strategy can become a
      platform technology for other lipophilic drugs to target tumors. 

PMID- 25987187
TI  - Global Surgery 2030: Evidence and solutions for achieving health, welfare, and
      economic development.

PMID- 25987189
TI  - Correlates of HIV Testing Among Men Who have Sex with Men in Three Urban Areas of
      Mozambique: Missed Opportunities for Prevention.
AB  - This is the first study to identify levels of recent HIV testing and associated
      factors among men who have sex with men (MSM) in Mozambique. Using data from
      Maputo (n = 493), Beira (n = 572), and Nampula/Nacala (n = 347), collected via
      respondent-driven sampling in 2011, and excluding those with prior known
      infection, we found that 30.4 % [95 % confidence interval (CI) 25.0-36.3 %], 42.1
      % (95 % CI 36.8-47.3 %) and 29.8 % (95 % CI 22.9-36.9 %), respectively, had
      recently tested for HIV (<=12 months), while between three and five out of 10 MSM
      had never tested. A range of factors was associated with recent HIV testing such
      as familiarity with the modes of transmission, knowledge of antiretroviral
      treatment for HIV, contact with peer educators and awareness of partner
      serostatus; yet, surprisingly recent healthcare utilization was not associated
      with recent testing. Findings provide evidence that structural and behavioral
      interventions among MSM may play an important role in increasing HIV testing. 

PMID- 25987188
TI  - Aurora kinase A in gastrointestinal cancers: time to target.
AB  - Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. During
      the last two decades, several studies have shown amplification and overexpression
      of Aurora kinase A (AURKA) in several GI malignancies. These studies demonstrated
      that AURKA not only plays a role in regulating cell cycle and mitosis, but also
      regulates a number of key oncogenic signaling pathways. Although AURKA inhibitors
      have moved to phase III clinical trials in lymphomas, there has been slower
      progress in GI cancers and solid tumors. Ongoing clinical trials testing AURKA
      inhibitors as a single agent or in combination with conventional chemotherapies
      are expected to provide important clinical information for targeting AURKA in GI
      cancers. It is, therefore, imperative to consider investigations of molecular
      determinants of response and resistance to this class of inhibitors. This will
      improve evaluation of the efficacy of these drugs and establish biomarker based
      strategies for enrollment into clinical trials, which hold the future direction
      for personalized cancer therapy. In this review, we will discuss the available
      data on AURKA in GI cancers. We will also summarize the major AURKA inhibitors
      that have been developed and tested in pre-clinical and clinical settings.

PMID- 25987190
TI  - Behavioral Economics Matters for HIV Research: The Impact of Behavioral Biases on
      Adherence to Antiretrovirals (ARVs).
AB  - Behavioral economics (BE) has been used to study a number of health behaviors
      such as smoking and drug use, but there is little knowledge of how these insights
      relate to HIV prevention and care. We present novel evidence on the prevalence of
      the common behavioral decision-making errors of present-bias, overoptimism, and
      information salience among 155 Ugandan HIV patients, and analyze their
      association with subsequent medication adherence. 36 % of study participants are
      classified as present-biased, 21 % as overoptimistic, and 34 % as having salient
      HIV information. Patients displaying present-bias were 13 % points (p = 0.006)
      less likely to have adherence rates above 90 %, overoptimistic clients were 9 %
      points (p = 0.04) less likely, and those not having salient HIV information were
      17 % points (p < 0.001) less likely. These findings indicate that BE may be used
      to screen for future adherence problems and to better design and target
      interventions addressing these behavioral biases and the associated suboptimal
      adherence.

PMID- 25987191
TI  - Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility
      gene for idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Idiopathic scoliosis is a spinal deformity affecting
      approximately 3% of otherwise healthy children or adolescents. The etiology is
      still largely unknown but has an important genetic component. Genome-wide
      association studies have identified a number of common genetic variants that are
      significantly associated with idiopathic scoliosis in Asian and Caucasian
      populations, rs11190870 close to the LBX1 gene being the most replicated finding.
      PURPOSE: The aim of the present study was to investigate the genetics of
      idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene
      study of four variants previously shown to be associated with idiopathic
      scoliosis and exome sequencing of idiopathic scoliosis patients with a severe
      phenotype to identify possible novel scoliosis risk variants. STUDY DESIGN: This
      was a case control study. PATIENT SAMPLE: A total of 1,739 patients with
      idiopathic scoliosis and 1,812 controls were included. OUTCOME MEASURE: The
      outcome measure was idiopathic scoliosis. METHODS: The variants rs10510181,
      rs11190870, rs12946942, and rs6570507 were genotyped in 1,739 patients with
      idiopathic scoliosis and 1,812 controls. Exome sequencing was performed on pooled
      samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare
      missense, nonsense, or splice site variants were selected for individual
      genotyping in the 1,739 cases and 1,812 controls. In addition, the 5'UTR,
      noncoding exon and promoter regions of LBX1, not covered by exome sequencing,
      were Sanger sequenced in the 100 pooled samples. RESULTS: Of the four candidate
      genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a
      highly significant association to idiopathic scoliosis in 1,739 cases and 1,812
      controls (p=7.0*10(-18)). We identified 20 novel variants by exome sequencing
      after filtration and an initial genotyping validation. However, we could not
      verify any association to idiopathic scoliosis in the large cohort of 1,739 cases
      and 1,812 controls. We did not find any variants in the 5'UTR, noncoding exon and
      promoter regions of LBX1. CONCLUSIONS: Here, we confirm LBX1 as a susceptibility
      gene for idiopathic scoliosis in a Scandinavian population and report that we are
      unable to find evidence of other genes of similar or stronger effect.

PMID- 25987192
TI  - Cues, quantification, and agreement in language comprehension.
AB  - We investigated factors that affect the comprehension of subject-verb agreement
      in English, using quantification as a window into the relationship between
      morphosyntactic processes in language production and comprehension. Event-related
      brain potentials (ERPs) were recorded while participants read sentences with
      grammatical and ungrammatical verbs, in which the plurality of the subject noun
      phrase was either doubly marked (via overt plural quantification and
      morphological marking on the noun) or singly marked (via only plural morphology
      on the noun). Both acceptability judgments and the ERP data showed heightened
      sensitivity to agreement violations when quantification provided an additional
      cue to the grammatical number of the subject noun phrase, over and above plural
      morphology. This is consistent with models of grammatical comprehension that
      emphasize feature prediction in tandem with cue-based memory retrieval. Our
      results additionally contrast with those of prior studies that showed no effects
      of plural quantification on agreement in language production. These findings
      therefore highlight some nontrivial divergences in the cues and mechanisms
      supporting morphosyntactic processing in language production and comprehension. 

PMID- 25987193
TI  - Associating approximate paths and temporal sequences of noisy detections:
      Application to the recovery of spatio-temporal cancer cell trajectories.
AB  - In this paper we address the problem of recovering spatio-temporal trajectories
      of cancer cells in phase contrast video-microscopy where the user provides the
      paths on which the cells are moving. The paths are purely spatial, without
      temporal information. To recover the temporal information associated to a given
      path we propose an approach based on automatic cell detection and on a graph
      based shortest path search. The nodes in the graph consist of the projections of
      the cell detections onto the geometrical cell path. The edges relate nodes which
      correspond to different frames of the sequence and potentially to the same cell
      and trajectory. In this directed graph we search for the shortest path and use it
      to define a temporal parametrization of the corresponding geometrical cell path.
      An evaluation based on 286 paths of 7 phase contrast microscopy videos shows that
      our algorithm allows to recover 92% of trajectory points with respect to the
      associated ground truth. We compare our method with a state-of-the-art algorithm
      for semi-automated cell tracking in phase contrast microscopy which requires
      interactively placed starting points for the cells to track. The comparison shows
      that supporting geometrical paths in combination with our algorithm allow us to
      obtain more reliable cell trajectories. 

PMID- 25987194
TI  - Auxins action on Glycine max secretory phospholipase A2 is mediated by the
      interfacial properties imposed by the phytohormones.
AB  - Secretory phospholipase A2 (sPLA2) are soluble enzymes that catalyze the
      conversion of phospholipids to lysophospholipids and free fatty acids at membrane
      interfaces. The effect of IAA and IPA auxins over the activity of recombinant
      sPLA2 isoforms from Glycine max was studied using membrane model systems
      including mixed micelles and Langmuir lipid monolayers. Both phytohormones
      stimulate the activity of both plant sPLA2 using DLPC/Triton mixed micelles as
      substrate. To elucidate the mechanism of action of the phytohormones, we showed
      that both auxins are able to self-penetrate lipid monolayers and cause an
      increment in surface pressure and an expansion of lipid/phytohormone mixed
      interfaces. The stimulating effect of auxins over phospholipase A2 activity was
      still present when using Langmuir mixed monolayers as organized substrate
      regardless of sPLA2 source (plant or animal). All the data suggest that the
      stimulating effect of auxins over sPLA2 is due to a more favorable interfacial
      environment rather to a direct effect over the enzyme. 

PMID- 25987195
TI  - Near-Infrared Spectroscopy Hemoglobin Index Measurement During Fluid Challenge: A
      Prospective Study in Cardiac Surgery Patients.
AB  - OBJECTIVE: Little is known about changes in near-infrared spectroscopy-derived
      tissue hemoglobin index (HbI). The authors tested the hypothesis that absolute
      values and changes in brain hemoglobin index (HbIb) and skeletal muscle
      hemoglobin index (HbIm) could differ from the reference arterial hemoglobin (Hb)
      during fluid challenge. DESIGN: A prospective, monocenter observational study.
      SETTING: A 16-bed cardiac surgical intensive care unit in a teaching university
      hospital. PARTICIPANTS: Fifty consecutive adult patients. INTERVENTIONS:
      Investigation before and after a fluid challenge. MEASUREMENTS AND MAIN RESULTS:
      Simultaneous comparative Hb, HbIb and HbIm data points were collected from a
      blood-gas analyzer and the EQUANOX device (Nonin Medical Inc., Plymouth, MN).
      Correlations were determined by linear regression. No significant relationship
      was found between absolute values of Hb and HbIb before (R(2)= 0.04, p = 0.627)
      and after (R(2) = 0.00006, p = 0.956) fluid challenge. No significant
      relationship was found between absolute values of Hb and HbIm before (R(2)=
      0.030, p = 0.226) and after (R(2) = 0.05, p = 0.117) the fluid challenge. No
      significant relationship was found between changes in Hb and HbIb (R(2)= 0.26, p
      = 0.263) and between changes in Hb and HbIm (R(2) = 0.001, p = 0.801) after the
      fluid challenge. Bland-Altman analysis showed a poor concordance between changes
      in Hb and HbIb, and changes in Hb and HbIm, with large limits of agreement.
      CONCLUSIONS: HbIb and HbIm cannot be used to provide continuous noninvasive
      estimation of Hb, and trends in HbIb and HbIm cannot be considered as noninvasive
      surrogates for the trend in Hb after cardiac surgery.

PMID- 25987196
TI  - Pre- and Post-Bypass Platelet Function Testing With Multiple Electrode
      Aggregometry and TEG Platelet Mapping in Cardiac Surgery.
AB  - OBJECTIVES: To investigate the differences between pre- and post-cardiopulmonary
      bypass platelet function tests and to examine whether post-bypass tests could
      predict postoperative bleeding. DESIGN: A prospective cohort study. SETTING: A
      tertiary cardiothoracic center. PARTICIPANTS: Fifty-four patients presenting for
      cardiac surgery. INTERVENTIONS: Pre- and post-bypass platelet function tests with
      TEG Platelet Mapping (PM) and Multiple Electrode Aggregometry (Multiplate - MEA)
      were performed. MEASUREMENTS AND MAIN RESULTS: The results of the paired samples
      were compared. Outcomes including blood loss in the first 4 and 12 hours
      postoperatively and requirement for resternotomy also were recorded and
      regression analyses performed to establish predictive factors. Tests using
      adenosine diphosphate (ADP) and arachidonic acid as stimulators for platelet
      aggregation showed significant differences pre- and post-bypass, with both MEA
      and PM showing greater inhibition in platelet function after bypass (p<0.01).
      However, there was no significant change in MEA TRAP values with cardiopulmonary
      bypass (p = 0.79) There was no relationship between post-bypass platelet function
      and the reduction in measured platelet function and blood loss in the
      postoperative period. CONCLUSIONS: Post-bypass platelet function testing showed
      reductions in ADP and arachidonic acid-triggered aggregation but not in TRAP
      triggered aggregation compared with pre-bypass testing. There was no relationship
      between the post-bypass tests and bleeding.

PMID- 25987197
TI  - Reliability and validity of the Korean version of the Scale for the Assessment of
      Thought, Language, and Communication.
AB  - BACKGROUND: Our study aimed to assess the inter-rater and test-retest
      reliability, as well as concurrent and convergent validity, of the Korean version
      of the Scale for the Assessment of Thought, Language, and Communication (TLC
      scale). METHODS: The factor solutions and psychometric properties of the Korean
      version of the TLC scale were evaluated among 167 schizophrenia inpatients (study
      subjects) at two sites in South Korea. Using Pearson's correlation, the
      concurrent and convergent validities of each of the factor solutions were
      represented by the correlations with the scores on the Clinical Language Disorder
      Rating Scale, Brief Psychiatric Rating Scale, Young Mania Rating Scale, and
      Calgary Depression Scale. Using receiver operating characteristics curves, the
      optimal cut-off score for the Korean version of the TLC scale to distinguish
      between study subjects with and without disorganized speech, was identified.
      RESULTS: The results showed that the Korean version of the TLC scale has a three
      factor solution: fluent disorganization, speech emptiness, and speech
      peculiarity. In addition, the interrater reliability of the Korean version of the
      TLC scale was moderately good (intraclass correlation coefficient = 0.51) and its
      test-retest reliability was very good (Pearson's correlation coefficient = 0.94).
      For detecting the current presence of disorganized speech, the optimal cut-off
      total score on the TLC scale was proposed to be 8 points (sensitivity = 88.1%;
      specificity = 82.9%). LIMITATIONS: Psychometric tools covering cognitive
      functions were not used in our study. CONCLUSIONS: The Korean version of the TLC
      scale is a promising psychometric method for examining formal thought disorder
      (FTD) and disorganized speech in schizophrenia patients.

PMID- 25987198
TI  - The effects of aggression on symptom severity and treatment response in a trial
      of cognitive behavioral therapy for panic disorder.
AB  - BACKGROUND: Previous research suggests that patients with panic disorder exhibit
      higher levels of aggression than patients with other anxiety disorders. This
      aggression is associated with more severe symptomatology and interpersonal
      problems. However, few studies have examined whether higher levels of aggression
      are associated with a worse treatment response in this population. METHODS: The
      present study sought to examine the association of aggression with panic disorder
      symptom severity in a sample of 379 patients who participated in a trial
      examining long-term strategies for the treatment of panic disorder. RESULTS: We
      found that aggression was significantly associated with higher baseline levels of
      panic disorder symptoms, anxiety, depression, and functional impairment. Further,
      we found that patients higher in aggression did not achieve the same level of
      improvement in general anxiety symptoms during treatment compared to patients
      lower in aggression, even when controlling for baseline anxiety symptom severity.
      CONCLUSION: These results suggest that more research is needed concerning
      patients with anxiety disorders with higher aggression, as they may be a group in
      need of additional treatment considerations.

PMID- 25987199
TI  - Glucagon-like peptide-1 regulates mitochondrial biogenesis and tau
      phosphorylation against advanced glycation end product-induced neuronal insult:
      Studies in vivo and in vitro.
AB  - Our previous study has proved that glucagon-like peptide-1 (GLP-1), which is
      developed to treat type 2 diabetes, has a significant effect on neuroprotection
      against advanced glycation end product (AGE)-induced neuronal insult in vitro
      models of diabetes-related Alzheimer's disease (AD). However, the molecular
      mechanisms remain to be elucidated and it is not clear whether GLP-1 receptor
      mediates the down-regulation effects on AGE-induced AD-like changes in vivo. This
      study aims to explore the effect and mechanisms of GLP-1 receptor agonists (GLP
      1RA) against the AGE-dependent signaling pathway both in vitro and in vivo. In
      this study, we demonstrated that GLP-1RA could inhibit oxidative stress and
      repair mitochondrial damage in addition to decreasing tau hyperphosphorylation in
      PC12 cells treated with AGEs. Importantly, we first observed AGEs in the
      circulatory system could induce tau hyperphosphorylation after we injected AGEs
      (1MUg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote
      mitochondrial biogenesis and antioxidant system via regulating peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) signaling
      pathway in vivo besides down-regulating the activity of glycogen synthase kinase
      3beta (GSK-3beta) to reverse tau hyperphosphorylation directly. Collectively, our
      results suggest that GLP-1RA protects neurons against AGE-induced tau
      hyperphosphorylation via regulating GSK-3beta and PGC-1alpha two cooperative
      signaling pathways.

PMID- 25987200
TI  - Improving spatial updating accuracy in absence of external feedback.
AB  - Updating the position of an earth-fixed target during whole-body rotation seems
      to rely on cognitive processes such as the utilization of external feedback.
      According to perceptual learning models, improvement in performance can also
      occur without external feedback. The aim of this study was to assess spatial
      updating improvement in the absence and in the presence of external feedback.
      While being rotated counterclockwise (CCW), participants had to predict when
      their body midline had crossed the position of a memorized target. Four
      experimental conditions were tested: (1) Pre-test: the target was presented 30
      degrees  in the CCW direction from participant's midline. (2) Practice: the
      target was located 45 degrees  in the CCW direction from participant's midline.
      One group received external feedback about their spatial accuracy (Mackrous and
      Simoneau, 2014) while the other group did not. (3) Transfer T(30)CCW: the target
      was presented 30 degrees  in the CCW direction to evaluate whether improvement in
      performance, during practice, generalized to other target eccentricity. (4)
      Transfer T(30)CW: the target was presented 30 degrees  in the clockwise (CW)
      direction and participants were rotated CW. This transfer condition evaluated
      whether improvement in performance generalized to the untrained rotation
      direction. With practice, performance improved in the absence of external
      feedback (p=0.004). Nonetheless, larger improvement occurred when external
      feedback was provided (ps=0.002). During T(30)CCW, performance remained better
      for the feedback than the no-feedback group (p=0.005). However, no group
      difference was observed for the untrained direction (p=0.22). We demonstrated
      that spatial updating improved without external feedback but less than when
      external feedback was given. These observations are explained by a mixture of
      calibration processes and supervised vestibular learning.

PMID- 25987201
TI  - JWH-018 impairs sensorimotor functions in mice.
AB  - Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) is a synthetic
      cannabinoid agonist illegally marketed in "Spice" and "herbal blend" for its
      psychoactive effect greater than those produced by cannabis. In rodents JWH-018
      reproduces typical effects of (-)-Delta(9)-THC or Dronabinol(r) (Delta(9)-THC)
      such as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on
      sensorimotor functions are still unknown. Therefore, the aim of the present study
      is to investigate the effect of acute administration of JWH-018 (0.01-6mg/kg
      i.p.) on sensorimotor functions in male CD-1 mice and to compare its effects with
      those caused by the administration of Delta(9)-THC (0.01-6mg/kg i.p.). A specific
      battery of behavioral tests were adopted to investigate effects of cannabinoid
      agonists on sensorimotor functions (visual, auditory, tactile) and neurological
      changes (convulsion, myoclonia, hyperreflexia) while video-tracking analysis was
      used to study spontaneous locomotion. JWH-018 administration inhibited
      sensorimotor responses at lower doses (0.01-0.1mg/kg), reduced spontaneous
      locomotion at intermediate/high doses (1-6mg/kg) and induced convulsions,
      myoclonia and hyperreflexia at high doses (6mg/kg). Similarly, administration of
      Delta(9)-THC reduced sensorimotor responses in mice but it did not inhibit
      spontaneous locomotion and it did not induce neurological alterations. All
      behavioral effects and neurological alterations were prevented by the
      administration of the selective CB1 receptor antagonist/inverse agonist 1-(2,4
      dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3
      carboxamide (AM 251). For the first time these data demonstrate that JWH-018
      impairs sensorimotor responses in mice. This aspect should be carefully evaluated
      to better understand the potential danger that JWH-018 may pose to public health,
      with particular reference to decreased performance in driving and hazardous
      works.

PMID- 25987202
TI  - Association between exploratory activity and social individuality in genetically
      identical mice living in the same enriched environment.
AB  - We previously reported that inbred, genetically identical mice living in one
      enriched environment develop individual behavioral trajectories, indicating
      increasingly different levels of spatial exploratory behavior as quantified by
      roaming entropy. Cumulative roaming entropy (cRE) correlated positively with
      adult hippocampal neurogenesis, a type of plasticity involved in the flexible
      integration of new information into existing contexts (Freund et al., 2013). The
      study on which we report here was done in parallel to that first experiment, but
      here we acquired detailed observational data on the behavior of individual mice.
      Roaming entropy (RE) was again assessed in real-time with an antenna-based system
      over the entire experimental period of 3months. Compared to the least active mice
      in the enclosure (low number of antenna contacts), the most active animals showed
      tendencies of increased socially interactive behavior in the final observation
      block whereas least active mice displayed more self-related behavior (non-social
      local exploration and play). When looking at roaming behavior, we discovered that
      RE correlated negatively with latent factors representing social exploratory and
      non-social exploratory and play behavior. Adult neurogenesis could not be studied
      in the present cohort but we do know that under identical conditions, cumulative
      RE correlated positively with adult hippocampal neurogenesis. We can thus
      hypothesize that the mice with more exploratory experience in terms of areal
      coverage (as quantified by RE) and related greater levels of adult hippocampal
      plasticity, might also be the ones that were less involved in interactions within
      the group and, hence, more individualistic. While this remains to be confirmed
      experimentally, the present data suggest that the described mechanism of
      individualization, which has previously been shown to be hippocampus-dependent,
      has a social component. 

PMID- 25987204
TI  - Circuitry and plasticity of the dorsal horn--toward a better understanding of
      neuropathic pain.
AB  - Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key
      substrate for development of neuropathic pain following peripheral nerve injury.
      Advances in genetic engineering, tracing techniques and opto-genetics are leading
      to a much better understanding of the complex circuitry of the spinal DH and the
      radical changes evoked in such circuitry by nerve injury. These changes can be
      viewed at multiple levels including: synaptic remodeling including enhanced
      excitatory and reduced inhibitory drive, morphological and electrophysiological
      changes which are observed both to primary afferent inputs as well as DH neurons,
      and ultimately circuit-level rewiring which leads to altered connectivity and
      aberrant processing of sensory inputs in the DH. The DH should not be seen in
      isolation but is subject to important descending modulation from the brainstem,
      which is further dysregulated by nerve injury. Understanding which changes relate
      to specific disease-states is essential, and recent work has aimed to stratify
      patient populations in a mechanistic fashion. In this review we will discuss how
      such pathophysiological mechanisms may lead to the distressing sensory phenomena
      experienced by patients suffering neuropathic pain, and the relationship of such
      mechanisms to current and potential future treatment modalities.

PMID- 25987203
TI  - 27-Hydroxycholesterol contributes to disruptive effects on learning and memory by
      modulating cholesterol metabolism in the rat brain.
AB  - Cholesterol metabolism is important for neuronal function in the central nervous
      system (CNS). The oxysterol 27-hydroxycholesterol (27-OHC) is a cholesterol
      metabolite that crosses the blood-brain barrier (BBB) and may be a useful
      substitutive marker for neurodegenerative diseases. However, the effects of 27
      OHC on learning and memory and the underlying mechanisms are unclear. To
      determine this mechanism, we investigated learning and memory and cholesterol
      metabolism in rat brain following the injection of various doses of 27-OHC into
      the caudal vein. We found that 27-OHC increased cholesterol levels and
      upregulated the expression of liver X receptor-alpha (LXR-alpha) and adenosine
      triphosphate (ATP)-binding cassette transporter protein family member A1 (ABCA1).
      In addition, 27-OHC decreased the expression of 3-hydroxy-3-methylglutaryl-CoA
      reductase (HMG-CR) and low-density lipoprotein receptor (LDLR) in rat brain
      tissues. These findings suggest that 27-OHC may negatively modulate cognitive
      effects and cholesterol metabolism in the brain.

PMID- 25987205
TI  - Downregulation of survivin regulates adult hippocampal neurogenesis and
      apoptosis, and inhibits spatial learning and memory following traumatic brain
      injury.
AB  - Survivin, a unique member of the inhibitor of the apoptosis protein (IAP) family,
      has been suggested to play a crucial role in promoting the cell cycle and
      mediates mitosis during embryonic development. However, the role of survivin
      following traumatic brain injury (TBI) in adult neurogenesis and apoptosis in the
      mouse dentate gyrus (DG) remains only partially understood. We adopted adenovirus
      mediated RNA interference (RNAi) as a means of suppressing the expression of
      survivin and observed its effects on adult regeneration and neurological function
      in mice after brain injury. The mice were subjected to TBI, and the ipsilateral
      hippocampus was then examined using reverse transcription polymerase chain
      reaction (RT-PCR) and Western blotting analyses. Brain slices were stained for 5'
      bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX). Our data showed that
      survivin knockdown inhibits the proliferation and differentiation of neural
      precursor cells (NPCs) in the DG of the hippocampus soon after TBI. Furthermore,
      downregulation of survivin results in a significant increase in programmed cell
      death in the DG, as assessed using terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) double
      staining. The Morris water maze (MWM) test was adopted to evaluate neurological
      function, which confirmed that knockdown of survivin worsened the memory capacity
      that was already compromised following TBI. Survivin in adult mice brains after
      TBI can be successfully down-regulated by RNAi, which inhibited adult hippocampal
      neurogenesis, promoted apoptotic cell death, and resulted in a negative role in
      the recovery of dysfunction following injury.

PMID- 25987206
TI  - Walter Rudolf Hess (1881-1973).

PMID- 25987207
TI  - Thyroid hormone level is associated with motor symptoms in de novo Parkinson's
      disease.
AB  - Sympathetic denervation has been observed not only in the myocardium but also in
      the thyroid of patients with Parkinson's disease (PD). We investigated whether
      sympathetic denervation as indicated by decreased cardiac (123)I-meta
      iodobenzylguanidine uptake is associated with the levels of thyroid hormones and
      whether the levels of thyroid hormones affect clinical manifestations in patients
      with PD. The subjects were 75 patients with de novo PD and 20 age-matched healthy
      controls. We examined the levels of thyroid-stimulating hormone, free
      triiodothyronine, and free thyroxine, and evaluated the associations of these
      levels with cardiac (123)I-meta-iodobenzylguanidine uptake and motor symptoms.
      The results showed that the free triiodothyronine level was below the normal
      range in 29 patients (approximately 40 %) and was significantly lower in the
      patients with PD than in the controls. The decreased free triiodothyronine level
      was associated with akinetic-rigid motor subtype and washout ratio of cardiac
      (123)I-meta-iodobenzylguanidine scintigraphy. The free triiodothyronine level
      negatively correlated with disease severity. Thyroid-stimulating hormone level
      was within normal range. However, its level was lower in patients with tremor
      dominant type or mixed type than in those with akinetic-rigid type. All
      correlations of these variables with the levels of thyroid hormones remained
      statistically significant on multiple regression analysis. Our results suggest
      that the thyroid hormone level, especially the free triiodothyronine level, is
      closely related to motor symptoms in patients with de novo PD. Further studies
      are needed to clarify whether the decreased hormone levels have functional roles
      in motor and non-motor symptoms. 

PMID- 25987209
TI  - Ultrasound and electric pulses for transdermal drug delivery enhancement: Ex vivo
      assessment of methods with in vivo oriented experimental protocols.
AB  - In our present study we focus on two physical enhancement methods for transdermal
      drug delivery: ultrasound and electric pulses either alone or in combination.
      Great emphasis has been given on the design of the experimental system and
      protocols, so the results and the conclusions drawn from them would have greater
      relevance for in vivo use and later translation into clinical practice. Our
      results show a statistically significant enhancement of calcein delivery (after
      one hour of passive diffusion following treatment) already after 5 minutes of
      ultrasound application, or only 6 * 100 short high voltage electrical pulses. We
      also experimented with combinations of the two enhancement methods hoping for
      synergistic effects, however, the results showed no evident drastic improvement
      over single method. Looking closer at physics of both methods, this absence of
      synergy in our in vivo oriented experimental setting is not surprising. The
      mechanism of action of both methods is the creation of aqueous pathways in the
      stratum corneum leading to increased skin permeability. However, when used in
      combination (regardless of the order of methods), the second method was
      unsuccessful in adding many new aqueous pathways in the stratum corneum, as it
      acted preferentially near the sites of the existing ones.

PMID- 25987208
TI  - Treatment and outcome of children and adolescents with N-methyl-D-aspartate
      receptor encephalitis.
AB  - The objective of this study is to describe the treatment and outcome of children
      and adolescents with N-methyl-D-aspartate receptor (NMDA-R) encephalitis. A
      retrospective study of children and adolescents with NMDA-R encephalitis was
      performed by the French Paraneoplastic Neurological Syndrome Reference Center
      between January 1, 2007 and December 31, 2012. The modified Rankin scale (mRS)
      was used to assess outcome. Thirty-six children and adolescents with NMDA-R
      encephalitis were studied. All of the patients received first-line immunotherapy
      (corticosteroids, intravenous immunoglobulins or plasma exchange), and 81%
      received second-line immunotherapy (rituximab or cyclophosphamide). Median time
      between first-line and second-line treatment was 26 days. During the first 24
      months, 30 of 36 patients (83%) achieved a good outcome (mRS <= 2) and 20 of 36
      patients (56%) achieved complete recovery (mRS = 0). Median time to good outcome
      and to complete recovery was 6 and 24 months, respectively. Three patients (8%)
      relapsed, one patient died. In multivariate analysis, age >12 years was a
      predictor of good outcome and initial mRS <= 3 was a predictor of complete
      recovery. Despite a higher rate of patients who received second-line
      immunotherapy, the outcome of the patients in the present series was very similar
      to the outcome reported in previous series. The present study highlights the need
      for clinical trials to determine the optimal treatment of NMDA-R encephalitis.

PMID- 25987210
TI  - Formulating powder-device combinations for salmeterol xinafoate dry powder
      inhalers.
AB  - Using salmeterol xinafoate (SX) as an active pharmaceutical ingredient, the
      effects of carrier lactose particle type, total lactose fines content and device
      resistance on dry powder inhaler performance were investigated in vitro. To mimic
      drug levels in commercial preparations, interactive mixtures containing 0.58% w/w
      SX were prepared by low shear tumble mixing. Three types of milled inhalation
      grade lactose were used (Lactohale((r)) LH 200, Respitose((r)) ML006 and ML001)
      and the concentration of fine lactose (Lactohale((r)) 300) added was varied. The
      in vitro deposition of each mixture was studied using a next generation impactor
      and inhaler devices exhibiting different resistances,
      Rotahaler((r))<Aerolizer((r))<Handihaler((r)). Aerosol performance was evaluated
      based on the emitted dose (ED), mass median aerodynamic diameter (MMAD) +/-
      geometric standard deviation (GSD) and fine particle fraction (FPF). Increases of
      up to eight-fold in FPF were observed with increasing intrinsic fine lactose
      content. The addition of extra fine lactose increased the FPF further, although
      the effect diminished as more fines were added. The Aerolizer produced the best
      aerosol performance with any given powder blend, although suitable formulations
      were identified for each device as defined by the a priori success criteria: >80%
      ED and MMAD +/- GSD between 1-5 MUm. The results confirmed the factors under
      investigation to be important determinants of product performance, but
      demonstrated using realistic conditions how individual factor impact may be
      enhanced or mitigated by inter-dependency.

PMID- 25987211
TI  - Effects of formulation design on niacin therapeutics: mechanism of action,
      metabolism, and drug delivery.
AB  - Niacin is a highly effective, lipid regulating drug associated with a number of
      metabolically induced side effects such as prostaglandin (PG) mediated flushing
      and hepatic toxicity. In an attempt to reduce the development of these adverse
      effects, scientists have investigated differing methods of niacin delivery
      designed to control drug release and alter metabolism. However, despite
      successful formulation of various orally based capsule and tablet delivery
      systems, patient adherence to niacin therapy is still compromised by adverse
      events such as PG-induced flushing. While the primary advantage of orally dosed
      formulations is ease of use, alternative delivery options such as transdermal
      delivery or polymeric micro/nanoparticle encapsulation for oral administration
      have shown promise in niacin reformulation. However, the effectiveness of these
      alternative delivery options in reducing inimical effects of niacin and
      maintaining drug efficacy is still largely unknown and requires more in-depth
      investigation. In this paper, we present an overview of niacin applications, its
      metabolic pathways, and current drug delivery formulations. Focus is placed on
      oral immediate, sustained, and extended release niacin delivery as well as
      combined statin and/or prostaglandin antagonist niacin formulation. We also
      examine and discuss current findings involving transdermal niacin formulations
      and polymeric micro/nanoparticle encapsulated niacin delivery. 

PMID- 25987212
TI  - Insulin complexation with hydroxypropyl-beta-cyclodextrin: Spectroscopic
      evaluation of molecular inclusion and use of the complex in gel for healing of
      pressure ulcers.
AB  - The pressure ulcer healing is a complex process and difficult to be achieved.
      Insulin is known to promote wound healing, and when complexed with cyclodextrin
      presents improved solubility, stability and biological activity. Complexation of
      insulin with hydroxypropyl-beta-cyclodextrin (HPbetaCD) was performed in this
      work through the coprecipitation method, providing the inclusion complex
      (HPbetaCD-I). The spectroscopic techniques used to analyze the complex were H(1)
      NMR, FT-Raman and FT-IR/ATR. A gel containing the HPbetaCD-I complex was prepared
      and a clinical study was conducted in patients with pressure ulcers. The
      spectroscopic techniques allowed to confirm the complex formation through the
      inclusion of aromatic amino acids, such as phenylalanine present in the HPbetaCD
      cavity. Data obtained from the FT-Raman and FT-IR/ATR techniques, combined with
      the H(1) NMR results, showed the effectiveness of these techniques in evaluating
      the inclusion complex of HPbetaCD with insulin. Clinical studies demonstrated
      tissue revitalization and a trend (p=0.06) for a significant difference between
      the healing effect of the control gel and that with HPbetaCD-I complex. The
      creation of the gel prepared with insulin and HPbetaCD-I complex and its use in
      patients with pressure ulcers appears to be promising in wound healing and its
      possible use in hospital care. 

PMID- 25987213
TI  - Preface to the special issue: "Mode of action of environmental pollutants and
      insecticides".

PMID- 25987214
TI  - The aryl hydrocarbon receptor (AhR) mediates resistance to apoptosis induced in
      breast cancer cells.
AB  - The aryl hydrocarbon receptor (AhR) is well known as a ligand binding
      transcription factor regulating various biological effects. Previously we have
      shown that long-term exposure to estrogen in breast cancer cells caused not only
      down regulation of estrogen receptor (ER) but also overexpression of AhR. The AhR
      interacts with several cell signaling pathways associated with induction of
      tyrosine kinases, cytokines and growth factors which may support the survival
      roles of AhR escaping from apoptosis elicited by a variety of apoptosis inducing
      agents in breast cancer. In this study, we studied the anti-apoptotic role of AhR
      in different breast cancer cells when apoptosis was induced by exposure to UV
      light and chemotherapeutic agents. Activation of AhR by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in AhR overexpressing breast cancer cells
      effectively suppressed the apoptotic response induced by UV-irradiation,
      doxorubicin, lapatinib and paclitaxel. The anti-apoptotic response of TCDD was
      uniformly antagonized by the treatment with 3'methoxy-4'nitroflavone (MNF), a
      specific antagonist of AhR. TCDD's survival action of apoptosis was accompanied
      with the induction of well-known inflammatory genes, such as cyclooxygenase-2
      (COX-2) and NF-kappaB subunit RelB. Moreover, TCDD increased the activity of the
      immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO), which metabolizes
      tryptophan to kynurenine (Kyn) and mediates tumor immunity. Kyn also acts as an
      AhR ligand like TCDD, and kyn induced an anti-apoptotic response in breast cancer
      cells. Accordingly, our present study suggests that AhR plays a pivotal role in
      the development of breast cancer via the suppression of apoptosis, and provides
      an idea that the use of AhR antagonists with chemotherapeutic agents may
      effectively synergize the elimination of breast cancer cells. 

PMID- 25987215
TI  - Luteolin suppresses TCDD-induced wasting syndrome in a cultured adipocyte model.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various toxic effects,
      including wasting syndrome, through activation of an aryl hydrocarbon receptor
      (AhR). Our previous report demonstrated that certain flavonoids inhibit the
      activation of AhR and suppress its DNA binding activity. In this study, we
      searched for an active compound among 13 flavonoids that suppressed TCDD-induced
      loss of lipid accumulation using 3T3-L1 adipocytes as a cell culture model for
      wasting syndrome. Two flavonoids, luteolin and epigallocatechin gallate,
      suppressed TCDD-induced loss of lipid accumulation in this model. We further
      investigated luteolin to clarify the underlying molecular mechanism and confirmed
      that luteolin inhibited nuclear translocation of AhR caused by TCDD. Luteolin
      also inhibited the TCDD-driven decrease in protein expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding
      protein alpha (C/EBPalpha). Although TCDD alone did not change protein expression
      of C/EBPbeta and C/EBPdelta, luteolin and TCDD up-regulated C/EBPdelta expression
      in a dose-dependent manner. On the other hand, TCDD significantly decreased DNA
      binding of C/EBPbeta and C/EBPdelta, and luteolin completely canceled TCDD
      decreased DNA binding of them. We conclude that luteolin suppresses the TCDD
      induced loss of lipid accumulation in 3T3-L1 adipocytes by preventing a decrease
      in protein expression of PPARgamma and C/EBPalpha, the master regulators of
      adipocyte differentiation and in DNA binding of C/EBPbeta and C/EBPdelta.
      Moreover, luteolin was rapidly incorporated and accumulated in 3T3-L1 adipocytes.
      Thus, luteolin is an attractive compound for the prevention of TCDD-induced
      wasting syndrome. 

PMID- 25987216
TI  - Association of PCBs and allergies in children.
AB  - Recently, the incidence rates of childhood allergies have been rising around the
      world. The presence of persistent chemical pollutants in the environment and
      exposure to air pollutants are often cited as potential causes of childhood
      allergies. Accordingly, epidemiological studies of the associations between
      exposure to low levels of pollutants and adverse health effects are essential.
      However, at present no useful biomarkers for evaluating such associations have
      been developed. Thus, using a molecular epidemiological approach we planned to
      identify candidate biomarkers of pollutant-induced adverse health effects that
      can be used in children. In asthmatic children, we found that the serum levels of
      several polychlorinated biphenyl (PCB) congener sub-types were significantly
      positively correlated with interleukin (IL)-8 mRNA expression, whereas in a sub
      group of children who displayed positive immunoglobulin E (IgE) responses to milk
      or egg proteins IL-22 mRNA expression was demonstrated to be useful for detecting
      the adverse health effects of environmental pollutants, particularly PCB
      congeners. In conclusion, the mRNA expression levels of IL-8 and IL-22 can be
      used to detect children who are at particular risk of adverse health events
      caused by environmental pollutants, especially PCBs. 

PMID- 25987217
TI  - The formulation makes the honey bee poison.
AB  - Dr. Fumio Matsumura's legacy embraced a passion for exploring environmental
      impacts of agrochemicals on non-target species such as bees. Why most
      formulations are more toxic to bees than respective active ingredients and how
      pesticides interact to cause pollinator decline cannot be answered without
      understanding the prevailing environmental chemical background to which bees are
      exposed. Modern pesticide formulations and seed treatments, particularly when
      multiple active ingredients are blended, require proprietary adjuvants and inert
      ingredients to achieve high efficacy for targeted pests. Although we have found
      over 130 different pesticides and metabolites in beehive samples, no individual
      pesticide or amount correlates with recent bee declines. Recently we have shown
      that honey bees are sensitive to organosilicone surfactants, nonylphenol
      polyethoxylates and the solvent N-methyl-2-pyrrolidone (NMP), widespread co
      formulants used in agrochemicals and frequent pollutants within the beehive.
      Effects include learning impairment for adult bees and chronic toxicity in larval
      feeding bioassays. Multi-billion pounds of formulation ingredients like NMP are
      used and released into US environments. These synthetic organic chemicals are
      generally recognized as safe, have no mandated tolerances, and residues remain
      largely unmonitored. In contrast to finding about 70% of the pesticide active
      ingredients searched for in our pesticide analysis of beehive samples, we have
      found 100% of the other formulation ingredients targeted for analysis. These
      'inerts' overwhelm the chemical burden from active pesticide, drug and personal
      care ingredients with which they are formulated. Honey bees serve as an optimal
      terrestrial bioindicator to determine if 'the formulation and not just the dose
      makes the poison'. 

PMID- 25987218
TI  - The Drosophila Sodium Channel 1 (DSC1): The founding member of a new family of
      voltage-gated cation channels.
AB  - It has been nearly three decades since the identification of the Drosophila
      Sodium Channel 1 (DSC1) gene from Drosophila melanogaster. The orthologs of the
      DSC1 gene have now been identified in other insect species including BSC1 from
      Blattella germanica. Functional analyses of DSC1/BSC1 channels in Xenopus oocytes
      reveal that DSC1 and BSC1 encode voltage-gated cation channels that are more
      permeable to Ca(2+) than to Na(+). Genetic and electrophysiological analyses show
      that knockout of the DSC1 gene in D. melanogaster causes behavioral and
      neurological modifications. In this review, we summarize major findings from
      recent studies and highlight a unique role of the DSC1 channel, distinct from
      that of the sodium channel, in regulating membrane excitability and modulating
      toxicity of pyrethroid insecticides. 

PMID- 25987219
TI  - Structure-activity relationship of imidazothiadiazole analogs for the binding to
      the ecdysone receptor of insect cells.
AB  - Diacylhydrazines are the first non-steroidal ecdysone agonists, and five
      compounds are used as insecticides in agriculture. After the discovery of
      diacylhydrazine-type compounds, numerous non-steroidal structures were reported
      as ecdysone agonists. Among various ecdysone agonists, imidazothiadiazoles are
      reported to be very potent in vitro; however, the experimental detail for the
      structure identification and bioassays are not stated in the paper (Holmwood and
      Schindler, Bioorg. Med. Chem. 17, 4064-4070, 2009). In our present study, we
      synthesized 18 imidazothiadiazole-type compounds and confirmed the chemical
      structures by spectrometric analyses. The binding activity of the synthesized
      compounds to the ecdysone receptor was evaluated in terms of the concentration
      required for 50% inhibition of [(3)H]ponasterone A incorporation [IC50 (M)] into
      lepidopteran (Sf-9), coleopteran (BCRL-Lepd-SL1), and dipteran (NIAS-AeAl2)
      cells. 6-(2-Chlorophenyl)-2-(trifluoromethyl)imidazo[2,1-b] [1,3,4]-thiadiazol-5
      yl)acrylamide analogs with CONHR (secondary amide) were very potent against Sf-9
      cells, but further alkylation (tertiary amide: CONR2) decreased the activity
      dramatically. Additionally, a primary amide analog (CONH2) was inactive. The
      activity also decreased 150-fold by the saturation of olefin region of the
      acrylamide moiety. In addition, various substituents were introduced at the 2
      position of the imidazothiadiazole ring to disclose the physicochemical
      properties of the substituents which are important for receptor binding. The
      activity increased by 7500-fold with the introduction of the CF2CF2CF3 group
      compared to the unsubstituted compound against Sf-9 cells. Quantitative structure
      activity relationship analysis for these substituents indicated that hydrophobic
      and electron-withdrawing groups were favorable for binding. Some of the compounds
      with strong receptor binding activity showed good larvicidal activity against
      Spodoptera litura. In contrast, the binding affinity of imidazothiadiazole
      analogs was low or not observed against dipteran and coleopteran cells. 

PMID- 25987220
TI  - Synergistic action of octopamine receptor agonists on the activity of selected
      novel insecticides for control of dengue vector Aedes aegypti (Diptera:
      Culicidae) mosquito.
AB  - Studying insecticide resistance in mosquitoes has attracted the attention of many
      scientists to elucidate the pathways of resistance development and to design
      novel strategies in order to prevent or minimize the spread and evolution of
      resistance. Here, we tested the synergistic action of piperonyl butoxide (PBO)
      and two octopamine receptor (OR) agonists, amitraz (AMZ) and chlordimeform (CDM)
      on selected novel insecticides to increase their lethal action on the fourth
      instar larvae of Aedes aegypti L. However, chlorfenapyr was the most toxic
      insecticide (LC50 = 193, 102, and 48 ng/ml, after 24, 48, and 72 h exposure,
      respectively) tested. Further, PBO synergized all insecticides and the most toxic
      combinatorial insecticide was nitenpyram even after 48 and 72 h exposure. In
      addition, OR agonists significantly synergized most of the selected insecticides
      especially after 48 and 72 h exposure. The results imply that the synergistic
      effects of amitraz are a promising approach in increasing the potency of certain
      insecticides in controlling the dengue vector Ae. aegypti mosquito. 

PMID- 25987222
TI  - Fumio Matsumura--accomplishments at the University of California, Davis, and in
      the Sierra Nevada Mountains.
AB  - Fumio Matsumura joined the University of California, Davis, faculty in 1987 where
      he served as founding director of the Center for Environmental Health Sciences,
      associate director of the U.C. Toxic Substances Research and Teaching Program,
      and chair of the Department of Environmental Toxicology. He was an active
      affiliate with the NIEHS-funded Superfund Basic Research Program and the NIH
      Comprehensive Cancer Center. He was in many instances a primary driver or
      otherwise involved in most activities related to environmental toxicology at
      Davis, including the education of students in environmental biochemistry and
      ecotoxicology. A significant part of his broad research program was focused on
      the long range transport of chemicals such as toxaphene, PCBs and related
      contaminants used or released in California to the Sierra Nevada mountains,
      downwind of the urban and agricultural regions of the state. He hypothesized that
      these chemical residues adversely affected fish and wildlife, and particularly
      the declining populations of amphibians in Sierra Nevada streams and lakes. Fumio
      and his students and colleagues found residues of toxaphene and PCBs at higher
      elevations, an apparent result of atmospheric drift and deposition in the
      mountains. Fumio and his wife Teruko had personal interests in, and a love of the
      mountains, as avid skiers, hikers, and outdoor enthusiasts. 

PMID- 25987223
TI  - Pyrethroid resistance in Culex pipiens mosquitoes.
AB  - Mosquitoes within the Culex pipiens complex are widely distributed and important
      in the transmission of many human diseases. Insecticides, pyrethroids in
      particular, remain a mainstay for control of these important vectors. In this
      paper we review what is known about the levels, mechanisms and fitness costs of
      pyrethroid resistance in Cx. pipiens. Pyrethroid resistance in Cx. pipiens is a
      global problem, and resistance ratios of up to 7000-fold have been found in
      larvae of field collected mosquitoes. However, there is considerable variation
      between populations, indicating significant geographic heterogeneity of the
      resistance. The two major mechanisms of resistance to pyrethroids in Culex are
      mutations in Vssc (target site insensitivity) and overexpression of cytochrome
      P450(s) (increased detoxification). The most frequently reported Vssc mutation is
      L1014F (i.e. kdr), which has been found throughout the world. The L1014S mutation
      has been found in Cx. p. pallens from Japan and China, and in Cx. p. pipiens from
      China. The L1014C mutation has only been reported for Cx. p. pipens molestus from
      China and the V1016G mutation has only been reported from Saudi Arabia. Studies
      on the P450s of Cx. pipiens have identified several that are overexpressed
      (measured as transcript levels) in pyrethroid resistant strains. CYP9M10 is
      consistently overexpressed in pyrethroid resistant Cx. pipiens from at least
      seven countries, suggesting this P450 might be of global importance in
      resistance. Both CYP9M10-mediated pyrethroid resistance and kdr have fitness
      costs in the absence of insecticides under certain environmental conditions.
      Research needs and future directions are discussed. 

PMID- 25987221
TI  - Unique biochemical and molecular biological mechanism of synergistic actions of
      formamidine compounds on selected pyrethroid and neonicotinoid insecticides on
      the fourth instar larvae of Aedes aegypti (Diptera: Culicidae).
AB  - We recently reported that formamidine pesticides such as amitraz and
      chlordimeform effectively synergize toxic actions of certain pyrethroid and
      neonicotinoid insecticides in some insect species on the 4th instar larvae of
      Aedes aegypti. Here we studied the biochemical basis of the synergistic actions
      of the formamidines in amplifying the toxicity of neonicotinoids and pyrethroids
      such as dinotefuran and thiamethoxam, as well as deltamethrin-fenvalerate type of
      pyrethroids. We tested the hypothesis that their synergistic actions are mediated
      by the octopamine receptor, and that the major consequence of octopamine receptor
      activation is induction of trehalase to increase glucose levels in the hemolymph.
      The results show that formamidines cause a significant up-regulation of the
      octopamine receptor and trehalase mRNA expressions. Furthermore, formamidines
      significantly elevate levels of free glucose when co-treated with dinotefuran,
      deltamethrin and fenvalerate, but not with permethrin or fenitrothion, which
      showed no synergistic toxic effects with formamidines. These results support the
      conclusion that the main mode of synergism is based on the ability to activate
      the octopamine receptor, which is particularly effective with insecticides
      causing hyperexcitation-induced glucose release and consequently leading to quick
      energy exhaustion. 

PMID- 25987224
TI  - Cytochrome P450s--Their expression, regulation, and role in insecticide
      resistance.
AB  - P450s are known to be critical for the detoxification and/or activation of
      xenobiotics such as drugs and pesticides and overexpression of P450 genes can
      significantly affect the disposition of xenobiotics in the tissues of organisms,
      altering their pharmacological/toxicological effects. In insects, P450s play an
      important role in detoxifying exogenous compounds such as insecticides and plant
      toxins and their overexpression can result in increased levels of P450 proteins
      and P450 activities. This has been associated with enhanced metabolic
      detoxification of insecticides and has been implicated in the development of
      insecticide resistance in insects. Multiple P450 genes have been found to be co
      overexpressed in individual insect species via several constitutive
      overexpression and induction mechanisms, which in turn are co-responsible for
      high levels of insecticide resistance. Many studies have also demonstrated that
      the transcriptional overexpression of P450 genes in resistant insects is
      regulated by trans and/or cis regulatory genes/factors. Taken together, these
      earlier findings suggest not only that insecticide resistance is conferred via
      multi-resistance P450 genes, but also that it is mediated through the interaction
      of regulatory genes/factors and resistance genes. This chapter reviews our
      current understanding of how the molecular mechanisms of P450 interaction/gene
      regulation govern the development of insecticide resistance in insects and our
      progress along the road to a comprehensive characterization of P450
      detoxification-mediated insecticide resistance. 

PMID- 25987225
TI  - Synthesis of photoreactive ivermectin B1a derivatives and their actions on
      Haemonchus and Bombyx glutamate-gated chloride channels.
AB  - Glutamate-gated chloride channels (GluCls) are inhibitory neurotransmitter
      receptors that are present only in invertebrates such as nematodes and insects.
      These channels are important targets of insecticidal, acaricidal, and
      anthelmintic macrolides such as avermectins, ivermectin (IVM), and milbemycins.
      To identify the amino acid residues that interact with IVM in GluCls, three IVM
      B1a derivatives with different photoreactive substitutions at C-13 were
      synthesized in the present study. These derivatives displayed low- or
      subnanomolar affinity for parasitic nematode (Haemonchus contortus) and silkworm
      (Bombyx mori) GluCls expressed in COS-1 cells. The derivatives also activated
      homomeric H. contortus GluCls expressed in Xenopus oocytes. The results indicate
      that synthesized photoreactive IVM B1a derivatives have superior affinity and
      functionality for chemically labeling the macrolide-binding site in GluCls. . 

PMID- 25987226
TI  - gamma-BHC: Its history and mystery--why is only gamma-BHC insecticidal?
AB  - Among BHC isomers (benzene hexachloride, C6H6Cl6, theoretically eight ones),
      seven isomers (alpha,beta,gamma,delta,epsilon,eta,iota) including one racemate
      (alpha) were isolated and their configurations were elucidated. Among the seven
      isomers, only gamma-BHC has a potent insecticidal activity. gamma-BHC poisoning
      symptoms accompanied by the violent tremor of the body, particularly in the legs
      and abnormal fluttering were consistently correlated with central nervous system
      effects, and the action was shown on the ganglia rather than on the isolated
      nerve cord. The excitatory effects of gamma-BHC poisoning on spontaneous activity
      and synaptic function in the sixth abdominal ganglion of the American cockroach
      result from the presynaptic action that causes an excessive release of
      acetylcholine. F. Matsumura found the phenomena of cross resistance between gamma
      BHC, cyclodiene insecticides and GABA (gamma-aminobutyric acid) antagonist,
      picrotoxinin, and concluded that the primary target of gamma-BHC is the
      picrotoxinin receptor in the GABA receptor Cl- ion channel complex (GABA-gated
      chloride channel) and its antagonistic action on GABA receptor results in an
      excessive release of Ach. In order to study the structure-activity relationship,
      a number of gamma-BHC analogs, in which one or two chlorine atoms on dl or meso
      position(s) of the gamma-BHC molecule were replaced by various substituents such
      as hydrogen, halogens other than chlorine and alkoxy groups, etc. were
      synthesized. In the case of dl type-analogs, there is an optimum volume for dl
      substituents, which corresponds to Cl. The question why gamma-BHC is insecticidal
      and other BHC isomers are not remains unsolved. 

PMID- 25987227
TI  - Comparison between the modes of action of novel meta-diamide and macrocyclic
      lactone insecticides on the RDL GABA receptor.
AB  - Macrocyclic lactones, avermectins, and milbemycins are widely used to control
      arthropods, nematodes, and endo- and ectoparasites in livestock and pets. Their
      main targets are glutamate-gated chloride channels. Furthermore, macrocyclic
      lactones reportedly interact with insect RDL gamma-aminobutyric acid (GABA)
      receptors, but their modes of action on insect RDL GABA receptors remain unknown.
      In this study, we attempted to better understand the modes of action of
      macrocyclic lactones on RDL GABA receptors. We observed that ivermectin and
      milbemectin behaved as allosteric agonists of the Drosophila RDL GABA receptor.
      G336A, G336S, and G336T mutations had profound effects on the activities of
      ivermectin and milbemectin, and a G336M mutation abolished the allosteric agonist
      and antagonist activities of these macrocyclic lactones. These results suggest
      that G336 in TM3 of the Drosophila RDL GABA receptor is important for the binding
      of macrocyclic lactones. Recently, it has been suggested that a novel RDL GABA
      receptor antagonist, 3-benzamido-N-(2-bromo-4-perfluoroisopropyl-6
      (trifluoromethyl)phenyl)-2-fluorobenzamide (meta-diamide 7), binds to the
      transmembrane intersubunit pocket near G336 in the Drosophila RDL GABA receptor.
      Thus, we compared the effects of mutations around G336 and A302 mutations in TM2
      on the activities of macrocyclic lactone and meta-diamide 7. The effects of
      L281C, V340Q, V340N, A302S, and A302N mutations on the activity of meta-diamide 7
      differed from those on ivermectin and milbemectin. Molecular modeling studies
      showed that macrocyclic lactones docked in the intersubunit pocket near G336 in
      the Drosophila RDL GABA receptor in the open state. In contrast, meta-diamide 7
      docked into the Drosophila RDL GABA receptor in the closed state. This suggests
      that the modes of action of macrocyclic lactone binding to the wild-type
      Drosophila RDL GABA receptor differ from those of meta-diamide binding. 

PMID- 25987228
TI  - RNA interference: Applications and advances in insect toxicology and insect pest
      management.
AB  - Since its discovery, RNA interference (RNAi) has revolutionized functional
      genomic studies due to its sequence-specific nature of post-transcriptional gene
      silencing. In this paper, we provide a comprehensive review of the recent
      literature and summarize the current knowledge and advances in the applications
      of RNAi technologies in the field of insect toxicology and insect pest
      management. Many recent studies have focused on identification and validation of
      the genes encoding insecticide target proteins, such as acetylcholinesterases,
      ion channels, Bacillus thuringiensis receptors, and other receptors in the
      nervous system. RNAi technologies have also been widely applied to reveal the
      role of genes encoding cytochrome P450 monooxygenases, carboxylesterases, and
      glutathione S-transferases in insecticide detoxification and resistance. More
      recently, studies have focused on understanding the mechanism of insecticide
      mediated up-regulation of detoxification genes in insects. As RNAi has already
      shown great potentials for insect pest management, many recent studies have also
      focused on host-induced gene silencing, in which several RNAi-based transgenic
      plants have been developed and tested as proof of concept for insect pest
      management. These studies indicate that RNAi is a valuable tool to address
      various fundamental questions in insect toxicology and may soon become an
      effective strategy for insect pest management. 

PMID- 25987229
TI  - Mutation and duplication of arthropod acetylcholinesterase: Implications for
      pesticide resistance and tolerance.
AB  - A series of common/shared point mutations in acetylcholinesterase (AChE) confers
      resistance to organophosphorus and carbamate insecticides in most arthropod
      pests. However, the mutations associated with reduced sensitivity to insecticides
      usually results in the reduction of catalytic efficiency and leads to a fitness
      disadvantage. To compensate for the reduced catalytic activity, overexpression of
      neuronal AChE appears to be necessary, which is achieved by a relatively recent
      duplication of the AChE gene (ace) as observed in the two-spotted spider mite and
      other insects. Unlike the cases with overexpression of neuronal AChE, the
      extensive generation of soluble AChE is observed in some insects either from a
      distinct non-neuronal ace locus or from a single ace locus via alternative
      splicing. The production of soluble AChE in the fruit fly is induced by chemical
      stress. Soluble AChE acts as a potential bioscavenger and provides tolerance to
      xenobiotics, suggesting its role in chemical adaptation during evolution. 

PMID- 25987231
TI  - Sodium-difluoro(oxalato)borate (NaDFOB): a new electrolyte salt for Na-ion
      batteries.
AB  - A new electrolyte salt, sodium-difluoro(oxalato)borate (NaDFOB), was synthesized
      and studied, which enables excellent reversible capacity and high rate capability
      when used in Na/Na0.44MnO2 half cells. NaDFOB has excellent compatibility with
      various common solvents used in Na-ion batteries, in strong contrast to the
      solvent dependent performances of NaClO4 and NaPF6. In addition, NaDFOB possesses
      good stability and generates no toxic or dangerous products when exposed to air
      and water. All these properties demonstrate that NaDFOB could be used to prepare
      high performance electrolytes for emerging Na-ion batteries. 

PMID- 25987230
TI  - Utilization of the human louse genome to study insecticide resistance and innate
      immune response.
AB  - Since sequencing the human body louse genome, substantial advances have occurred
      in the utilization of the information gathered from louse genomes and
      transcriptomes. Comparatively, the body louse genome contains far fewer genes
      involved in environmental response, such as xenobiotic detoxification and innate
      immune response. Additionally, the body louse maintains a primary bacterial
      endosymbiont, Candidatus Riesia pediculicola, and a number of bacterial pathogens
      that it vectors, which have genomes that are also reduced in size. Thus, human
      louse genomes offer unique information and tools for use in advancing our
      understanding of coevolution among vectors, endosymbionts and pathogens. In this
      review, we summarize the current literature on the extent of pediculicide
      resistance, the availability of new pediculicides and information establishing
      this organism as an efficient model to study how xenobiotic metabolism, which is
      involved in insecticide resistance, is induced and how insects modify their
      innate immune response upon bacterial challenge resulting in enhanced vector
      competence. 

PMID- 25987232
TI  - Erratum for Elagib et al., Jun Blockade of Erythropoiesis: Role for Repression of
      GATA-1 by HERP2.

PMID- 25987234
TI  - Comparison of the prognostic value of regadenoson and adenosine myocardial
      perfusion imaging.
AB  - BACKGROUND: Regadenoson is now widely used in single-photon emission computed
      tomography (SPECT) myocardial perfusion imaging (MPI). However, the prognostic
      value of abnormal stress perfusion findings with regadenoson vs adenosine are
      unclear. The aim of this study was to evaluate the prognostic value of
      regadenoson SPECT and to compare it to that of adenosine SPECT. METHODS AND
      RESULTS: 3698 consecutive patients undergoing either adenosine or regadenoson
      SPECT were assessed at 1 year for the endpoints of cardiovascular death and a
      composite endpoint of cardiovascular death or MI. Weighted Cox proportional
      hazards regression modeling with the inverse probability weighted (IPW)
      estimators method adjusting to propensity for agent was used to account for
      differences in baseline characteristics. Patients undergoing adenosine SPECT MPI
      had a significantly higher prevalence of smoking history, diabetes, hypertension,
      and prior myocardial infarction (P < .05, all). At 1 year of follow-up, there
      were 154 cardiovascular deaths and 204 with the composite endpoint of
      cardiovascular death or MI. Using IPW adjustment to propensity for agent in a
      model with stress agent, summed stress score (SSS) remained a significant
      predictor of the composite endpoint of cardiovascular death or MI (HR 1.36 CI
      1.28-1.46; P < .0001) as well as cardiovascular death (HR 1.38 CI 1.28-1.49; P <
      .0001). The interaction of SSS with agent was not significant. Similar findings
      were seen with summed difference score (SDS). CONCLUSIONS: SSS derived from
      either adenosine or regadenoson SPECT MPI is a significant predictor of events
      and provides incremental prognostic information beyond basic clinical variables.
      We have shown for the first time that use of regadenoson vs adenosine as stress
      agent does not modify the prognostic significance of SSS. Similar findings were
      seen with SDS.

PMID- 25987235
TI  - Professional oral health care reduces oral mucositis pain in patients treated by
      superselective intra-arterial chemotherapy concurrent with radiotherapy for oral
      cancer.
AB  - PURPOSE: Oral mucositis (OM) is a painful complication of radiation therapy (RT)
      for head and neck cancer. OM can compromise nutrition, require opioid analgesics
      and hospitalization for pain control, and lead to interruption of treatment.
      Severe oral mucositis appears inevitable in superselective intra-arterial
      chemotherapy concurrent with radiotherapy (SSIACRT), requiring management of OM
      for the patient. The objective of this study was to assess the utility of
      professional oral health care (POHC) for the management of OM in patients
      undergoing SSIACRT. METHODS: Thirty-three patients were enrolled in this study.
      The first 17 patients underwent SSIACRT before we created an oral management
      team, and thus did not receive POHC. The remaining 16 patients received POHC.
      Fever duration, duration of oral feeding difficulty, opioid usage, duration of
      opioid administration, duration of hospitalization, and number of hospital days
      from the end of irradiation to discharge were compared between these two groups.
      RESULTS: Median total dose of morphine during SSIACRT, median number of hospital
      days from end of irradiation to discharge, and duration of hospitalization all
      differed significantly between groups (P < 0.05). Duration of opioid
      administration, fever duration, and duration of oral feeding difficulty did not
      differ significantly between groups. CONCLUSIONS: These findings indicate that
      POHC may reduce opioid use and shorten the hospital stay. Such results might be
      obtained through infection control by POHC. This report appears to be the first
      study to evaluate the efficiency of POHC in SSIACRT for oral cancer from the
      perspective of mucositis pain and opioid use.

PMID- 25987236
TI  - Functional variants in CYP1B1, KRAS and MTHFR genes are associated with shorter
      telomere length in postmenopausal women.
AB  - Estrogens and antioxidants indirectly alleviate telomere attrition. However,
      available clinical data on the association between hormone exposure and telomere
      length are inconclusive. In the present study, we examined the effects of
      exogenous estrogen use and of some genetic factors implicated in estrogen
      metabolism and oxidative stress response on mean leukocyte telomere length. We
      studied 259 postmenopausal women. Genotyping was conducted for CYP1B1
      (rs1056836), COMT (rs4680), GSTP1 (rs1695), MnSOD (rs4880), KRAS (rs61764370),
      and MTHFR (rs1801133 and rs1801131) polymorphisms. Mean leukocyte telomere length
      was measured using a quantitative real-time PCR assay. In multivariate analysis
      we found no association between oral contraceptives or hormone replacement
      therapy (HRT) and mean leukocyte telomere length. The presence of variant alleles
      in CYP1B1, KRAS and MTHFR genes was statistically significantly associated with
      shorter mean leukocyte telomere length. Further, the data provided evidence for
      the effect modification of the association between HRT and mean leukocyte
      telomere length by the CYP1B1, KRAS and MTHFR genotypes. Our findings suggest
      that functionally relevant genetic variants within estrogen and folate metabolic
      pathways may influence telomere length. We propose these genetic factors should
      be taken into consideration when interpreting associations between hormone
      exposure and telomere length. 

PMID- 25987238
TI  - History, blood tests or skin prick testing? Is it possible to predict the
      severity of allergic reactions in children with IgE-mediated food allergy?

PMID- 25987239
TI  - Towards evidence based medicine for paediatricians.

PMID- 25987237
TI  - Increased levels of p21((CIP1/WAF1)) correlate with decreased chondrogenic
      differentiation potential in synovial membrane progenitor cells.
AB  - Cartilage injuries are a major concern in the field of orthopedics. They occur
      following trauma, as well as from a variety of pathological conditions including
      Osteoarthritis (OA). Although cartilage does not exhibit robust endogenous
      repair, it has been demonstrated that modulating the activity of p21 can increase
      the regenerative abilities of cartilage in vitro and in vivo. Since the synovial
      membrane is abundant with mesenchymal progenitor cells (MPCs) capable of
      differentiating into cartilage both in vitro and in vivo, we examined if p21
      expression levels varied between MPCs derived from normal vs. OA knee joints.
      Analysis of p21 at the mRNA and protein levels within normal and OA MPCs
      demonstrated differential levels of expression between these two groups, with OA
      MPCs having higher p21 expression levels. The higher levels of p21 in OA MPCs are
      also correlated with a decreased chondrogenic differentiation capacity and
      synovial inflammation, however, there was no evidence of senescence in the OA
      cells. The results of this study suggest that cell cycle regulation in MPCs may
      be altered in OA and that modulation of this pathway may have therapeutic
      potential once the mechanism by which this regulates stem/progenitor cells is
      better understood. 

PMID- 25987241
TI  - Cost-effectiveness of one-time genetic testing to minimize lifetime adverse drug
      reactions.
AB  - We evaluated the cost-effectiveness of one-time pharmacogenomic testing for
      preventing adverse drug reactions (ADRs) over a patient's lifetime. We developed
      a Markov-based Monte Carlo microsimulation model to represent the ADR events in
      the lifetime of each patient. The base-case considered a 40-year-old patient. We
      measured health outcomes in life years (LYs) and quality-adjusted LYs (QALYs) and
      estimated costs using 2013 US$. In the base-case, one-time genetic testing had an
      incremental cost-effectiveness ratio (ICER) of $43,165 (95% confidence interval
      (CI) is ($42,769,$43,561)) per additional LY and $53,680 per additional QALY (95%
      CI is ($53,182,$54,179)), hence under the base-case one-time genetic testing is
      cost-effective. The ICER values were most sensitive to the average probability of
      death due to ADR, reduction in ADR rate due to genetic testing, mean ADR rate and
      cost of genetic testing.

PMID- 25987242
TI  - A common polymorphism in the ABCB1 gene is associated with side effects of PGP
      dependent antidepressants in a large naturalistic Dutch cohort.
AB  - The drug efflux transporter permeability glycoprotein (PGP) and cytochrome P450
      (CYP) 2C19 are important for eliminating antidepressants from the brain and body.
      The ABCB1 gene, encoding for PGP, and CYP2C19 gene have several variants that
      could influence enzyme function and thereby the effect of PGP- and 2C19-dependent
      antidepressants. We investigated the association of antidepressant side effect
      and common genetic variation in 789 antidepressant users. In PGP-dependent
      antidepressant users, the A-allele of the rs2032588 single-nucleotide
      polymorphism (SNP) was associated with a lower number of side effects after
      adjusting for gender, age, dosage and duration of use, (B=-0.44, q=4.6 * 10(-3)).
      This association was different from and absent in non-PGP-dependent
      antidepressant users. Other SNP associations as well as an interaction analysis
      between the rs2032588 SNP and the CYP2C19 SNPs were not statistically significant
      after adjusting for covariates and multiple comparisons. The association of
      rs2032588 with antidepressant side effects suggests the involvement of the ABCB1
      genotype in the clinical pharmacology of PGP-dependent antidepressants. 

PMID- 25987244
TI  - Application of immobilized synthetic anti-lipopolysaccharide peptides for the
      isolation and detection of bacteria.
AB  - The molecular detection of microorganisms in liquid samples generally requires
      their enrichment or isolation. The aim of our study was to evaluate the capture
      and pre-concentration of bacteria by immobilized particular cationic
      antimicrobial peptides, called synthetic anti-lipopolysaccharide peptides (SALP).
      For the proof-of-concept and screening of different SALP, the peptides were
      covalently immobilized on glass slides, and the binding of bacteria was confirmed
      by microscopic examination of the slides or their scanning, in case of
      fluorescent bacterial cells. The most efficient SALP was further tethered to
      magnetic beads. SALP beads were used for the magnetic capture of Escherichia coli
      in liquid samples. The efficiency of this strategy was evaluated using polymerase
      chain reaction (PCR). Covalently immobilized SALP were capable of capturing
      bacteria in liquid samples. However, PCR was hampered by the unspecific binding
      of DNA to the positively charged peptide. We developed a method for DNA recovery
      by the enzymatic digestion of the peptide, which allowed for a successful PCR,
      though the method had its own adverse impact on the detection and, thus, did not
      allow for the reliable quantitative analysis of the pathogen enrichment.
      Immobilized SALP can be used as capture molecules for bacteria in liquid samples
      and can be recommended for the design of the assays or decontamination of the
      fluids. For the accurate subsequent detection of bacteria, DNA-independent
      methods should be used. 

PMID- 25987243
TI  - Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a
      single genetic signal centered on known risk allele HLA-DRB1*07:01.
AB  - Lapatinib is associated with a low incidence of serious liver injury. Previous
      investigations have identified and confirmed the Class II allele HLA-DRB1*07:01
      to be strongly associated with lapatinib-induced liver injury; however, the
      moderate positive predictive value limits its clinical utility. To assess whether
      additional genetic variants located within the major histocompatibility complex
      locus or elsewhere in the genome may influence lapatinib-induced liver injury
      risk, and potentially lead to a genetic association with improved predictive
      qualities, we have taken two approaches: a genome-wide association study and a
      whole-genome sequencing study. This evaluation did not reveal additional
      associations other than the previously identified association for HLA-DRB1*07:01.
      The present study represents the most comprehensive genetic evaluation of drug
      induced liver injury (DILI) or hypersensitivity, and suggests that investigation
      of possible human leukocyte antigen associations with DILI and other
      hypersensitivities represents an important first step in understanding the
      mechanism of these events. 

PMID- 25987245
TI  - A comparison of monomicrobial versus polymicrobial Enterococcus faecalis
      bacteriuria in a French University Hospital.
AB  - Enterococci are of considerable relevance in the hospital setting. Their most
      common location is the urinary tract, where they may be responsible for both
      colonization and infections. They are often associated with the presence of other
      microorganisms. The aim was to compare monomicrobial and polymicrobial
      Enterococcus faecalis bacteriuria. A retrospective study was performed on the
      demographic, clinical, and laboratory data of 299 patients who had presented with
      E. faecalis bacteriuria in 2012 at a University Hospital. The bacteriuria was
      polymicrobial in 46.1 % of cases and in 36.4 % of cases was responsible for a
      urinary tract infection. Infections appeared to be more prevalent in the
      polymicrobial than the monomicrobial group (42 % vs 32 %, p = 0.06). Half of the
      patients who presented with urinary tract colonization received antibiotic
      treatment (54/ out of 10). A multivariate analysis adjusted for age (adjusted
      odds ratio [AOR] = 1.02 per year, p = 0.006), gender (AOR = 2.2, p = 0.007), and
      clinical classification (colonization or infection, AOR = 1.6, p = 0.091), showed
      that diabetes mellitus (AOR = 2.0, p = 0.04), hospital length of stay exceeding
      28 days (AOR = 2.0, p = 0.03), and presence of a urinary catheter (AOR = 2.4, p =
      0.001) were all factors associated with polymicrobial E. faecalis bacteriuria. A
      reduction in the length of hospital stay and the use of urinary catheters would
      appear to be required to decrease the incidence of urinary tract colonization and
      infections by polymicrobial E. faecalis. Improper use of antibiotics to treat
      urinary tract colonization remains a major concern. 

PMID- 25987246
TI  - Influence of daily dosage and frequency of administration of rifampicin
      levofloxacin therapy on tolerance and effectiveness in 154 patients treated for
      prosthetic joint infections.
AB  - Data on the tolerance and effectiveness of rifampicin-levofloxacin combination
      therapy (RLCT) in patients treated for prosthetic joint infections (PJIs)
      according to daily dosage are lacking. A review of the clinical data from
      patients treated with RLCT for PJIs in a French referent center for PJIs was
      conducted. A total of 154 patients (75 F/79 M), with a median age of 64.1 years
      and median body weight of 83.1 kg, were included. The median daily dosages of
      rifampicin and levofloxacin were, respectively, 1,200 mg (range 300-2,100) and
      750 mg (range 500-1,500), corresponding to a mean daily dose per kg of,
      respectively, 16.2 +/- 4.3 mg/kg and 10.1 +/- 3.0 mg/kg. After a mean follow-up
      period of 55.6 +/- 27.1 months (range 24-236), 127 patients (82.5 %) were in
      remission. Adverse events attributable to rifampicin and levofloxacin were
      reported in 48 (31.2 %) and 13 (8.4 %) patients (p < 0.001), respectively.
      Patients who experienced rifampicin-related adverse events had been given higher
      rifampicin daily doses than the other patients (p = 0.04). The rifampicin daily
      dosage did not influence patient outcome and nor did the levofloxacin daily
      dosage on both tolerance and patient outcome. Our results suggest that adjusting
      rifampicin daily doses to the patient total body weight when combined with
      levofloxacin for the treatment of PJIs is associated with a poor tolerance. High
      daily doses of rifampicin (>600 mg) and levofloxacin (750 mg) do not improve
      patient outcome when compared to lower daily doses in this setting. 

PMID- 25987247
TI  - Amoxicillin plus temocillin as an alternative empiric therapy for the treatment
      of severe hospital-acquired pneumonia: results from a retrospective audit.
AB  - A formulary decision was made at a large provider of acute hospital services in
      Surrey to replace piperacillin/tazobactam with amoxicillin+temocillin for the
      empiric treatment of severe hospital-acquired pneumonia. This decision was made
      because the use of broad-spectrum-beta-lactam antibiotics is a known risk factor
      for Clostridium difficile infection (CDI) and for the selection of resistance.
      After the antibiotic formulary was changed, a retrospective audit was conducted
      to assess the effect of this change. Data from patients hospitalised between
      January 2011 and July 2012 for severe hospital-acquired pneumonia and treated
      empirically with piperacillin/tazobactam or amoxicillin+temocillin were reviewed
      retrospectively. Clinical characteristics of patients, data related to the
      episode of pneumonia, clinical success and incidence of significant diarrhoea and
      CDI were analysed. One hundred ninety-two episodes of severe hospital-acquired
      pneumonia in 188 patients were identified from hospital records. Ninety-eight
      patients received piperacillin/tazobactam and 94 amoxicillin+temocillin. At
      baseline, the two treatment groups were comparable, except that more patients
      with renal insufficiency were treated with piperacillin/tazobactam. Clinical
      success was comparable (80 versus 82 %; P = 0.86), but differences were observed
      between piperacillin/tazobactam and amoxicillin+temocillin for the rates of
      significant diarrhoea (34 versus 4 %, respectively; P < 0.0001) and for CDI (7
      versus 0 %, respectively; P < 0.0028). This preliminary study suggests that the
      combination amoxicillin+temocillin is a viable alternative to
      piperacillin/tazobactam for the treatment of severe hospital-acquired pneumonia.
      This combination appears to be associated with fewer gastrointestinal adverse
      events. Further studies are needed to evaluate the place of
      amoxicillin+temocillin as empiric treatment of severe hospital-acquired
      pneumonia. 

PMID- 25987248
TI  - Interspecific hybridization does not affect the level of fluctuating asymmetry
      (FA) in the Drosophila bipectinata species complex.
AB  - The Drosophila bipectinata species complex comprises of four very closely related
      species namely D. bipectinata, D. parabipectinata, D. malerkotliana and D.
      pseudoananassae. It was found that irrespective of the evolutionary divergence
      among the species, FA which is reflective of the developmental precision remains
      nearly same in four species. During the present study, the level of FA in
      different morphological traits was studied in interspecific hybrids and compared
      with that of parental species with the view that it would throw light on the
      degree of divergence between the parental species. If they have not diverged
      much, the interspecific hybrids may have a similar FA level, incompatibilities
      between their genomes being negligible. On the other hand, if there is
      substantial divergence, the level of FA may be higher due to incompatibility
      between the genomes of the parental species. The morphological traits taken were
      sternopleural bristle number and wing length in both males and females and
      ovariole number and sex-comb tooth number in females and males respectively.
      However, except in a few cases, we could not detect any significant differences
      in the level of FA in hybrids as compared to pure species. On the other hand, a
      number of abnormalities like poor viability, dystrophied ovaries, asymmetrical
      eyes etc., could be detected in hybrids from crosses involving D. pseudoananassae
      as one of the parents. Therefore, we conclude that specific developmental
      pathways are more susceptible to developmental disturbances due to genomic
      incompatibilities than the large complex system bringing about developmental
      stability. 

PMID- 25987249
TI  - Glypican-5 Increases Susceptibility to Nephrotic Damage in Diabetic Kidney.
AB  - Type 2 diabetes mellitus is a leading health issue worldwide. Among cases of
      diabetes mellitus nephropathy (DN), the major complication of type 2 diabetes
      mellitus, the nephrotic phenotype is often intractable to clinical intervention
      and demonstrates the rapid decline of renal function to end-stage renal disease.
      We recently identified the gene for glypican-5 (GPC5), a cell-surface heparan
      sulfate proteoglycan, as conferring susceptibility for acquired nephrotic
      syndrome and additionally identified an association through a genome-wide
      association study between a variant in GPC5 and DN of type 2 diabetes mellitus.
      In vivo and in vitro data showed a progressive increase of GPC5 in type 2 DN
      along with severity; the excess was derived from glomerular mesangial cells. In
      this study, diabetic kidney showed that accumulation of fibroblast growth factor
      (Fgf)2 strikingly induced progressive proteinuria that was avoided in Gpc5
      knockdown mice. The efficacy of Gpc5 inhibition was exerted through expression of
      the Fgf receptors 3 and 4 provoked in the diabetic kidney attributively.
      Extraglomerular Fgf2 was pathogenic in DN, and the deterrence of Gpc5 effectively
      inhibited the glomerular accumulation of Fgf2, the subsequent increase of
      mesangial extracellular matrix, and the podocytes' small GTPase activity. These
      findings elucidate the pivotal role of GPC5, identified as a susceptible gene in
      the genome-wide association study, in hyperglycemia-induced glomerulopathy.

PMID- 25987250
TI  - Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial
      Calcification in Mice.
AB  - Arterial medial calcification (AMC) is a hallmark of aging, diabetes, and chronic
      kidney disease. Smooth muscle cell (SMC) transition to an osteogenic phenotype is
      a common feature of AMC, and is preceded by expression of runt-related
      transcription factor 2 (Runx2), a master regulator of bone development. Whether
      SMC-specific Runx2 expression is required for osteogenic phenotype change and AMC
      remains unknown. We therefore created an improved targeting construct to generate
      mice with floxed Runx2 alleles (Runx2(f/f)) that do not produce truncated Runx2
      proteins after Cre recombination, thereby preventing potential off-target
      effects. SMC-specific deletion using SM22-recombinase transgenic allele mice
      (Runx2(DeltaSM)) led to viable mice with normal bone and arterial morphology.
      After vitamin D overload, arterial SMCs in Runx2(f/f) mice expressed Runx2,
      underwent osteogenic phenotype change, and developed severe AMC. In contrast,
      vitamin D-treated Runx2(DeltaSM) mice had no Runx2 in blood vessels, maintained
      SMC phenotype, and did not develop AMC. Runx2 deletion did not affect serum
      calcium, phosphate, fibroblast growth factor-23, or alkaline phosphatase levels.
      In vitro, Runx2(f/f) SMCs calcified to a much greater extent than those derived
      from Runx2(DeltaSM) mice. These data indicate a critical role of Runx2 in SMC
      osteogenic phenotype change and mineral deposition in a mouse model of AMC,
      suggesting that Runx2 and downstream osteogenic pathways in SMCs may be useful
      therapeutic targets for treating or preventing AMC in high-risk patients.

PMID- 25987251
TI  - Homozygosity and Heterozygosity for Null Col5a2 Alleles Produce Embryonic
      Lethality and a Novel Classic Ehlers-Danlos Syndrome-Related Phenotype.
AB  - Null alleles for the COL5A1 gene and missense mutations for COL5A1 or the COL5A2
      gene underlie cases of classic Ehlers-Danlos syndrome, characterized by fragile,
      hyperextensible skin and hypermobile joints. However, no classic Ehlers-Danlos
      syndrome case has yet been associated with COL5A2 null alleles, and phenotypes
      that might result from such alleles are unknown. We describe mice with null
      alleles for the Col5a2. Col5a2(-/-) homozygosity is embryonic lethal at
      approximately 12 days post conception. Unlike previously described mice null for
      Col5a1, which die at 10.5 days post conception and virtually lack collagen
      fibrils, Col5a2(-/-) embryos have readily detectable collagen fibrils, thicker
      than in wild-type controls. Differences in Col5a2(-/-) and Col5a1(-/-) fibril
      formation and embryonic survival suggest that alpha1(V)3 homotrimers, a rare
      collagen V isoform that occurs in the absence of sufficient levels of alpha2(V)
      chains, serve functional roles that partially compensate for loss of the most
      common collagen V isoform. Col5a2(+/-) adults have skin with marked
      hyperextensibility and reduced tensile strength at high strain but not at low
      strain. Col5a2(+/-) adults also have aortas with increased compliance and reduced
      tensile strength. Results thus suggest that COL5A2(+/-) humans, although unlikely
      to present with frank classic Ehlers-Danlos syndrome, are likely to have fragile
      connective tissues with increased susceptibility to trauma and certain chronic
      pathologic conditions. 

PMID- 25987252
TI  - Colonoscopy in rural communities: a systematic review of the frequency and
      quality.
AB  - INTRODUCTION: In this systematic review, the authors review studies of rural
      colonoscopy to determine specialty types providing rural colonoscopy and the
      quality of these procedures. METHODS: A systematic MEDLINE search was conducted
      for articles pertaining to rural colonoscopy. Inclusion criteria were rural
      location, report of quality outcomes, or report of endoscopy workforce in rural
      areas. Two investigators independently reviewed and abstracted included articles.
      The following information was obtained from each study: author identification,
      citation, study design, source of funding, study duration and follow-up, study
      population, sample size, study setting, population characteristics, outcomes and
      results. Standard abstraction forms were used to summarize and assess the quality
      of evidence. RESULTS: From 121 articles in the MEDLINE search, 11 met inclusion
      criteria. One additional article found from a reference list was included. Eleven
      articles from three countries reported on 8703 colonoscopies performed by 25
      rural generalists. Reach-the-cecum rates (RCR) ranged from 36% to 96.5% with more
      recent studies showing higher RCRs. Adenoma detection rates ranged from 16.6% to
      46%. The rate of complications was low in all studies. One study of the rural
      endoscopist workforce reported that general surgeons performed most rural
      colonoscopies in Canada. CONCLUSIONS: Rural generalist physicians can safely and
      effectively perform colonoscopies. More research is needed on the rural
      endoscopist workforce.

PMID- 25987253
TI  - Affinity maturation of T-cell receptor-like antibodies for Wilms tumor 1 peptide
      greatly enhances therapeutic potential.
AB  - WT1126 (RMFPNAPYL) is a human leukocyte antigen-A2 (HLA-A2)-restricted peptide
      derived from Wilms tumor protein 1 (WT1), which is widely expressed in a broad
      spectrum of leukemias, lymphomas and solid tumors. A novel T-cell-receptor (TCR)
      like single-chain variable fragment (scFv) antibody specific for the T-cell
      epitope consisting of the WT1/HLA-A2 complex was isolated from a human scFv phage
      library. This scFv was affinity-matured by mutagenesis combined with yeast
      display and structurally analyzed using a homology model. This monovalent scFv
      showed a 100-fold affinity improvement (dissociation constant (KD)=3 nm) and
      exquisite specificity towards its targeted epitope or HLA-A2(+)/WT1(+) tumor
      cells. Bivalent scFv-huIgG1-Fc fusion protein demonstrated an even higher avidity
      (KD=2 pm) binding to the T-cell epitope and to tumor targets and was capable of
      mediating antibody-dependent cell-mediated cytotoxicity or tumor lysis by
      chimeric antigen receptor-expressing human T- or NK-92-MI-transfected cells. This
      antibody demonstrated specific and potent cytotoxicity in vivo towards WT1
      positive leukemia xenograft that was HLA-A2 restricted. In summary, T-cell
      epitopes can provide novel targets for antibody-based therapeutics. By combining
      phage and yeast displays and scFv-Fc fusion platforms, a strategy for developing
      high-affinity TCR-like antibodies could be rapidly explored for potential
      clinical development. 

PMID- 25987254
TI  - Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti
      multiple myeloma activity in vitro and in vivo.
AB  - Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in
      multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely
      correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence
      that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established
      cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral
      vectors or transfection with synthetic mimics impaired growth and survival of MM
      cells and overcame the protective role of bone marrow stromal cells in vitro.
      Apoptotic and autophagy-associated cell death were triggered in MM cells on miR
      125b-5p ectopic expression. Importantly, we found that the anti-MM activity of
      miR-125b-5p was mediated via direct downregulation of IRF4 and its downstream
      effector BLIMP-1. Moreover, inhibition of IRF4 translated into downregulation of
      c-Myc, caspase-10 and cFlip, relevant IRF4-downstream effectors. Finally, in vivo
      intra-tumor or systemic delivery of formulated miR-125b-5p mimics against human
      MM xenografts in severe combined immunodeficient/non-obese diabetic mice induced
      significant anti-tumor activity and prolonged survival. Taken together, our
      findings provide evidence that miR-125b, differently from other hematologic
      malignancies, has tumor-suppressor activity in MM. Furthermore, our data provide
      proof-of-concept that synthetic miR-125b-5p mimics are promising anti-MM agents
      to be validated in early clinical trials. 

PMID- 25987255
TI  - Constitutive control of AKT1 gene expression by JUNB/CJUN in ALK+ anaplastic
      large-cell lymphoma: a novel crosstalk mechanism.
AB  - Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL)
      is an aggressive T-cell non-Hodgkin lymphoma characterized by the t(2;5),
      resulting in the overexpression of nucleophosmin (NPM)-ALK, which is known to
      activate the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of
      rapamycin (mTOR) pathway, resulting in cell cycle and apoptosis deregulation.
      ALK+ ALCL is also characterized by strong activator protein-1 (AP-1) activity and
      overexpression of two AP-1 transcription factors, CJUN and JUNB. Here, we
      hypothesized that a biologic link between AP-1 and AKT kinase may exist, thus
      contributing to ALCL oncogenesis. We show that JUNB and CJUN bind directly to the
      AKT1 promoter, inducing AKT1 transcription in ALK+ ALCL. Knockdown of JUNB and
      CJUN in ALK+ ALCL cell lines downregulated AKT1 mRNA and promoter activity and
      was associated with lower AKT1 protein expression and activation. We provide
      evidence that this is a transcriptional control mechanism shared by other cell
      types even though it may operate in a way that is cell context-specific. In
      addition, STAT3 (signal transducer and activator of transcription 3)-induced
      control of AKT1 transcription was functional in ALK+ ALCL and blocking of STAT3
      and AP-1 signaling synergistically affected cell proliferation and colony
      formation. Our findings uncover a novel transcriptional crosstalk mechanism that
      links AP-1 and AKT kinase, which coordinate uncontrolled cell proliferation and
      survival in ALK+ ALCL. 

PMID- 25987257
TI  - New insights into the mixing of gold and copper in a nanoparticle from a
      structural study of Au-Cu nanoalloys synthesized via a wet chemistry method and
      pulsed laser deposition.
AB  - Gold-copper nanoparticles (Au-Cu NPs) were elaborated by both chemical (polyol
      reduction method) and physical (laser deposition) routes. The size, composition
      and crystal structure of these bimetallic nanoalloys were then characterized by
      aberration corrected transmission electron microscopy (TEM). Using a one-pot
      polyol method, Au-Cu nanocubes (NCs) with nominal compositions Au3Cu and AuCu3
      were synthesized. The size and composition of the NCs were tuned by varying the
      amount and the ratio of Au(iii) and Cu(ii) ions used as metallic precursors in
      the reaction. While the particle shape and size were well-controlled, single
      particle X-ray spectroscopy showed that, irrespective of the targeted
      compositions, the Cu content in all NCs was about 11-12 at%, i.e. in both
      samples, the real composition was different from the nominal one. This was
      ascribed to an incomplete alloying of the two constituent metals of the alloy in
      the cubes due to different reduction kinetics of the two metallic precursors. To
      shed light on the alloying of gold and copper at the nanoscale, Au-Cu NPs with
      targeted compositions Au3Cu and AuCu3 were deposited on amorphous carbon by laser
      ablation of two monometallic sources, and their structural properties were
      studied by TEM. These studies show that Au-Cu nanoalloys were synthesized in both
      samples and that the complete mixing of Au and Cu atoms achieved with this
      synthesis technique led to the production of Au-Cu NPs with well-controlled
      compositions. These results constitute a first but major step towards a complete
      understanding of the details of kinetics and thermodynamics determining the
      mixing of gold and copper atoms at the nanoscale. Such an understanding is
      essential for producing Au-Cu bimetallic nanoalloys with well-defined structural
      properties via wet chemical synthesis. 

PMID- 25987256
TI  - Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid
      defect in a mouse model for Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by
      haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome
      biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress
      response. However, the mechanisms of p53 activation and its relevance for the
      erythroid defect remain elusive. Previous studies have indicated that activation
      of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main
      negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile,
      it is not clear whether this mechanism solely mediates the p53-dependent
      component found in DBA. To approach this question, we crossed our mouse model for
      RPS19-deficient DBA with Mdm2(C305F) knock-in mice that have a disrupted 5S RNP
      Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2(C305F) reversed
      the p53 response and improved expansion of hematopoietic progenitors in vitro,
      and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP-Mdm2
      interaction also led to selective defect in erythropoiesis. Our findings
      highlight the sensitivity of erythroid progenitor cells to aberrations in p53
      homeostasis mediated by the 5S RNP-Mdm2 interaction. Finally, we provide evidence
      indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may
      contribute to functional decline of the hematopoietic system in a cell-autonomous
      manner over time. 

PMID- 25987259
TI  - Dialysate Sodium: Choosing the Optimal Hemodialysis Bath.
AB  - Fluid overload in patients undergoing hemodialysis contributes to cardiovascular
      morbidity and is a major cause of hospitalizations. It is often addressed by
      reinforcing the importance of a low-salt diet with patients and challenging
      estimated dry weights. More recently, interest has shifted toward the dialysate
      sodium prescription as a strategy to improve fluid overload and its adverse
      sequelae. The availability of high-flux high-efficiency dialysis in conjunction
      with the need to ensure its tolerability for patients has resulted in an increase
      in dialysate sodium prescriptions from 120 to >=140 mEq/L. However, we are now
      tackling the unforeseen consequences associated with high dialysate sodium
      prescriptions. High dialysate sodium concentration is associated with high
      interdialytic weight gain, a commonly used surrogate for hypervolemia
      contributing to hypertension. The association between mortality and high
      dialysate sodium concentration remains controversial with conflicting data. It is
      clear that fluid management in the diverse end-stage renal disease population is
      extremely complex and more clinical trials are needed. In the meantime, while
      patients require treatments and clinical decisions need to be made, this review
      article attempts to summarize the current evidence for individualized dialysate
      sodium prescriptions based on patients' volume status, comorbid conditions,
      plasma sodium level, and hemodynamic response to dialysis therapy. 

PMID- 25987258
TI  - Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General
      Population Cohort.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common in the elderly, but the cause
      is often not identifiable. Some posit that age-related reductions in glomerular
      filtration rate (GFR) and increases in albuminuria are normal, whereas others
      suggest that they are a consequence of vascular disease. STUDY DESIGN: Cross
      sectional analysis of a substudy of a prospective cohort. SETTING & PARTICIPANTS:
      AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study. PREDICTOR: Exposure
      to higher blood pressure in midlife. OUTCOMES & MEASUREMENTS: Measured GFR using
      plasma clearance of iohexol and urine albumin-creatinine ratio. RESULTS: GFR was
      measured in 805 participants with mean age in midlife and late life of 51.0+/-5.8
      and 80.8+/-4.0 (SD) years, respectively. Mean measured GFR was 62.4+/-16.5
      mL/min/1.73 m(2) and median albuminuria was 8.0 (IQR, 5.4-16.5) mg/g. Higher
      midlife systolic and diastolic blood pressures were associated with lower later
      life GFRs. Associations persisted after adjustment. Higher midlife systolic and
      diastolic blood pressures were also associated with higher albumin-creatinine
      ratios, and associations remained significant even after adjustment. LIMITATIONS:
      This is a study of survivors, and people who agreed to participate in this study
      were healthier than those who refused. Blood pressure may encompass effects of
      the other risk factors. Results may not be generalizable to populations of other
      races. We were not able to adjust for measured GFR or albuminuria at the midlife
      visit. CONCLUSIONS: Factors other than advanced age may account for the high
      prevalence of CKD in the elderly. Midlife factors are potential contributing
      factors to late-life kidney disease. Further studies are needed to identify and
      treat midlife modifiable factors to prevent the development of CKD.

PMID- 25987260
TI  - Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in
      Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction
      of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II
      Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).
AB  - BACKGROUND: Low serum bicarbonate level has been reported to be an independent
      predictor of kidney function decline and mortality in patients with chronic
      kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in
      patients with and without diabetes. We aimed to specifically investigate the
      association of serum bicarbonate level with kidney disease progression and
      cardiovascular outcome in a cohort of patients with type 2 diabetes and
      nephropathy. STUDY DESIGN: Post hoc analysis of 2 multicenter randomized
      controlled trials. SETTING & PARTICIPANTS: 2,628 adults with type 2 diabetes and
      nephropathy. FACTOR: Serum bicarbonate level. OUTCOMES: Incidence of: (1) end
      stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3)
      all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial
      infarction), and (5) heart failure. MEASUREMENTS: Serum bicarbonate was measured
      at baseline as total carbon dioxide. Associations of baseline serum bicarbonate
      level with end points were investigated using Cox regression models. Serum
      bicarbonate levels were studied as a continuous variable and stratified in
      quartiles. Follow-up was 2.8+/-1.0 (SD) years. RESULTS: Cox regression analyses
      showed that serum bicarbonate level had inverse associations with incident ESRD
      (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of
      ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These
      associations were independent of age, sex, and cardiovascular risk factors, but
      disappeared after adjustment for baseline estimated glomerular filtration rate
      (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the
      quartile with the lowest bicarbonate (<=21 mEq/L) versus the quartile with normal
      bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level
      with cardiovascular events and heart failure. LIMITATIONS: Post hoc analysis and
      single measurement of serum bicarbonate. CONCLUSIONS: In this cohort of patients
      with type 2 diabetes with nephropathy, serum bicarbonate level associations with
      kidney disease end points were not retained after adjustment for estimated
      glomerular filtration rate, which is in contrast to results of earlier studies in
      nondiabetic populations.

PMID- 25987262
TI  - Humoral Immune Response and Allograft Function in Kidney Transplantation.
AB  - HLA antibodies can damage a kidney transplant. In January 2013, consensus
      guidelines from The Transplantation Society were published regarding technical
      aspects of HLA antibody determination, as well as their potential significance in
      the pre- and posttransplantation periods. During the past 2 years, new studies
      have been reported, but controversies remain. In this article, these new data
      related to HLA antibodies in kidney transplantation are reviewed and compared to
      relevant prior research. Pretransplantation sensitization issues are discussed,
      including the new more sensitive assays (flow cytometry and solid-phase
      immunoassays such as Luminex single-antigen bead assays). A positive complement
      dependent cytotoxicity crossmatch remains an absolute contraindication to
      transplantation, although a positive flow cytometry crossmatch is only a relative
      contraindication. Positivity only by solid-phase assays increases the risk for
      acute rejection and transplant loss, but acceptable cutoffs are not defined. The
      sensitizing effect of red blood cell transfusions is substantiated. Following
      allograft failure, continued immunosuppression decreases the risk of
      sensitization, whereas overall, the effect of nephrectomy remains uncertain.
      Regarding the posttransplantation period, new data are available concerning the
      timing and significance of donor-specific antibodies (DSA). Whereas some centers
      report DSA appearance after years, others detect DSA within months. The
      prominence of class II DSA, especially DQ, in the posttransplantation period is
      noted. The relevance of non-HLA antibodies is discussed, including anti
      endothelial cell antibodies, major histocompatibility complex class I chain
      related protein A antibodies, and angiotensin II type 1 receptor autoantibodies. 

PMID- 25987261
TI  - Kidney diseases associated with monoclonal immunoglobulin M-secreting B-cell
      lymphoproliferative disorders: a case series of 35 patients.
AB  - BACKGROUND: Kidney diseases associated with immunoglobulin M (IgM) monoclonal
      gammopathy are poorly described, with few data for patient outcomes and renal
      response. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 35 patients from 8
      French departments of nephrology were retrospectively studied. Inclusion criteria
      were: (1) detectable serum monoclonal IgM, (2) estimated glomerular filtration
      rate (eGFR) < 60mL/min/1.73m(2) and/or proteinuria with protein excretion >
      0.5g/d and/or microscopic hematuria, and (3) kidney biopsy showing monoclonal
      immunoglobulin deposits and/or lymphomatous B-cell renal infiltration. All
      patients received chemotherapy, including rituximab-based regimens in 8 cases.
      PREDICTORS: Patients were classified into 3 groups according to renal pathology:
      glomerular AL amyloidosis (group 1; n=11), nonamyloid glomerulopathies (group 2;
      n=15, including 9 patients with membranoproliferative glomerulonephritis), and
      tubulointerstitial nephropathies (group 3; n=9, including cast nephropathy in 5,
      light-chain Fanconi syndrome in 3, and isolated tumor infiltration in 1).
      OUTCOMES: Posttreatment hematologic response (>=50% reduction in serum monoclonal
      IgM and/or free light chain level) and renal response (>=50% reduction in 24-hour
      proteinuria or eGFR>=30mL/min/1.73m(2) in patients with glomerular and
      tubulointerstitial disorders, respectively). RESULTS: Nephrotic syndrome was
      observed in 11 and 6 patients in groups 1 and 2, respectively. Patients in group
      3 presented with acute kidney injury (n=7) and/or proximal tubular dysfunction
      (n=3). Waldenstrom macroglobulinemia was present in 26 patients (8, 12, and 6 in
      groups 1, 2, and 3, respectively). Significant lymphomatous interstitial
      infiltration was observed in 18 patients (4, 9, and 5 patients, respectively).
      Only 9 of 29 evaluable patients had systemic signs of symptomatic hematologic
      disease (2, 5, and 2, respectively). In groups 1, 2, and 3, respectively,
      hematologic response was achieved after first-line treatment in 3 of 9, 9 of 10,
      and 5 of 6 evaluable patients, while renal response occurred in 5 of 10, 9 of 15,
      and 5 of 8 evaluable patients. LIMITATIONS: Retrospective study; insufficient
      population to establish the impact of chemotherapy. CONCLUSIONS: IgM monoclonal
      gammopathy is associated with a wide spectrum of renal manifestations, with an
      under-recognized frequency of tubulointerstitial disorders.

PMID- 25987264
TI  - Kidney Donation: What Might It Mean for Women Wishing to Become Pregnant.

PMID- 25987265
TI  - Fabrication of continuous electrospun filaments with potential for use as medical
      fibres.
AB  - Soft tissue injuries represent a substantial and growing social and economic
      burden. Medical fibres are commonly used to repair these injuries during surgery.
      Patient's outcomes are, however, not promising with around 40% of surgical
      repairs failing within the first few months after surgery due to poor tissue
      regeneration. The application of nanofibrous filaments and yarns as medical
      fibres and scaffolds has been suggested to improve soft tissue regeneration and
      enhance the quality of the repair. However, due to a lack of robustness and
      reliability of the current fabrication methods, continuous nanofibrous filaments
      cannot be manufactured and scaled up in industrial settings and are not currently
      available for clinical use. We have developed a robust and automated method that
      enables the manufacture of continuous electrospun filaments and which has the
      potential to be integrated into existing textile production lines. The technology
      uses a wire guide to form submicrofibres in a dense, narrow mesh which can be
      detached as a long and continuous thread. The thread can then be stretched and
      used to create multifilament yarns which can imitate the hierarchical
      architecture of tissues such as tendons and ligaments. Electrospun polydioxanone
      yarns produced by this method showed improved cellular proliferation and adhesion
      when compared to medical monofilament fibres in current clinical use. In vivo,
      the electrospun yarns showed a good safety profile with mild foreign body
      reaction and complete degradation within 5 months after implantation. These
      results suggest that this filament collection method has the potential to become
      a useful platform for the fabrication of future medical textiles.

PMID- 25987263
TI  - Patient safety issues in CKD: core curriculum 2015.

PMID- 25987266
TI  - Platelets and vascular inflammation of the brain.
AB  - There is emerging evidence that platelets have an important role in inflammation
      beyond their involvement in hemostasis. Platelets can contribute to inflammatory
      reactions via crosstalk both with immune cells and endothelial cells. Inflamed
      vessels are characterized by the presence of activated endothelial cells. These
      activated endothelial cells upregulate receptors necessary for leukocyte
      recruitment, but also for the adhesion of platelets. Subsequently, immune cells
      can bind to platelets through adhesion receptors presented on the platelet
      surface, thus supporting leukocyte recruitment to the vessel wall. There are
      several neurological diseases associated with vascular inflammation including
      multiple sclerosis (MS) and stroke. Increased markers of platelet activation
      could be demonstrated in patients suffering from MS compared to healthy
      individuals. Reports from murine models indicate that platelets may be of
      importance for disease progression and severity by mediating leukocyte
      recruitment as one potential underlying mechanism. Blocking platelet function
      disease severity was considerably ameliorated. Moreover, processes of tissue
      remodelling may be influenced by platelet derived mediators. Whether a role of
      platelets for vascular inflammation can be extrapolated to further neurological
      diseases will have to be investigated in further in depth experimental and
      clinical trials. CONCLUSION: Platelets and platelet associated mechanisms may
      offer novel starting points to understand neurovascular diseases from a different
      point of view and to develop novel approaches to access the disease.

PMID- 25987267
TI  - Paradoxical low-flow low-gradient aortic stenosis: advanced severe disease, a new
      entity or a progression of disease?

PMID- 25987268
TI  - Diastolic dysfunction and atrial fibrillation.

PMID- 25987269
TI  - Complete revascularisation or culprit artery only in cardiogenic shock: the real
      shock is the lack of data!

PMID- 25987270
TI  - Zinc Regulates Lipid Metabolism and MMPs Expression in Lipid Disturbance Rabbits.
AB  - Lipid disturbance induced by high-fat diet is a worldwide problem, and it can
      induce inflammation and oxidative stress in vivo. Zinc is considered as an
      antioxidant, anti-inflammatory agent. Since matrix metalloprotease 2 (MMP2) and
      matrix metalloprotease 9 (MMP9)'s expressions are changed under many pathological
      conditions, we would like to know how zinc affects lipid metabolism and MMP2,
      MMP9's expressions in the lipid disturbance rabbits. Twenty-four male New Zealand
      white rabbits were randomly divided into four groups. Each group had six rabbits,
      and they were fed with regular diet, high-fat diet, high-fat diet+zinc, and
      regular diet+zinc separately for 12 weeks. High-fat diet induced lipid
      disturbance significantly which raised the level of aspartate aminotransferase
      (p<0.01) and alanine transaminase (p<0.05) in the high-fat diet group, but zinc
      supplement reversed this phenomenon (p<0.05). Zinc did not reduce total
      cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p>0.05), but it
      lowered triglyceride (TG) and raised high-density lipoprotein cholesterol (HDL-C)
      (p<0.01). Zinc also reduced high-sensitivity C-reactive protein (hs-CRP) (p<0.01)
      and interleukin-6 (IL-6)'s expressions (p<0.05). Zinc reduced the epicardial
      adipose tissue and alleviated the hepatic steatosis. Zinc suppressed MMP2 and
      MMP9's expressions in vivo, but it did not alleviate the aorta fatty streak's
      severity in the lipid disturbance rabbits. Zinc protected the liver, reduced TG,
      hs-CRP, and IL-6 and raised HDL-C in the lipid disturbance rabbits. Zinc
      suppressed MMP2 and MMP9's expressions in vivo, but it did not alleviate the
      severity of aorta fatty streak induced by the high-fat diet.

PMID- 25987271
TI  - An improvised head support to facilitate endotracheal intubation in the lateral
      position.

PMID- 25987272
TI  - Corrections.

PMID- 25987273
TI  - Corrections.

PMID- 25987274
TI  - The first illustrations of neurons by Camillo Golgi.

PMID- 25987275
TI  - Asia's battle against brain fever.

PMID- 25987276
TI  - Daniel Lowenstein: medicine from a mountain top.

PMID- 25987277
TI  - Losing sleep.

PMID- 25987278
TI  - Lifeline.

PMID- 25987279
TI  - Atheism for clever people.

PMID- 25987280
TI  - Actors acting out neurology.

PMID- 25987282
TI  - Gastrointestinal dysfunction in Parkinson's disease.
AB  - Our understanding of dysfunction of the gastrointestinal system in patients with
      Parkinson's disease has increased substantially in the past decade. The entire
      gastrointestinal tract is affected in these patients, causing complications that
      range from oral issues, including drooling and swallowing problems, to delays in
      gastric emptying and constipation. Additionally, small intestinal bacterial
      overgrowth and Helicobacter pylori infection affect motor fluctuations by
      interfering with the absorption of antiparkinsonian drugs. The multifaceted role
      of the gastrointestinal system in Parkinson's disease necessitates a specific and
      detailed assessment and treatment plan. The presence of pervasive alpha-synuclein
      deposition in the gastrointestinal tract strongly implicates this system in the
      pathogenesis of Parkinson's disease. Future studies elucidating the role of the
      gastrointestinal tract in the pathological progression of Parkinson's disease
      might hold potential for early disease detection and development of
      neuroprotective approaches. 

PMID- 25987284
TI  - Headache arising from idiopathic changes in CSF pressure.
AB  - New onset of sudden or progressive headache can have various causes, including
      disorders of intracranial pressure (ICP). Headache is the most common-and often
      the presenting-symptom of both intracranial hypertension and intracranial
      hypotension syndromes, which can be symptomatic or idiopathic. Despite the
      widespread availability of diagnostic tests, including ocular ophthalmoscopy,
      neuroimaging, and measurement of CSF pressure, delays in diagnosis or
      misdiagnosis of idiopathic intracranial hypertension and spontaneous intracranial
      hypotension remain common. If left untreated, idiopathic intracranial
      hypertension and spontaneous intracranial hypotension produce highly disabling
      headaches, and threaten vision, hearing, and in rare cases, brain function and
      life. To improve the diagnosis of idiopathic intracranial hypertension and
      spontaneous intracranial hypotension, changes in the overall diagnostic strategy
      for headaches will be necessary in most care centres. Improved understanding of
      CSF physiology and the mechanisms of idiopathic intracranial hypertension and
      spontaneous intracranial hypotension will guide the development of new
      treatments. 

PMID- 25987283
TI  - Epidemiology, pathophysiology, diagnosis, and management of intracranial artery
      dissection.
AB  - Spontaneous intracranial artery dissection is an uncommon and probably
      underdiagnosed cause of stroke that is defined by the occurrence of a haematoma
      in the wall of an intracranial artery. Patients can present with headache,
      ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass
      effect, mostly on the brainstem. Although intracranial artery dissection is less
      common than cervical artery dissection in adults of European ethnic origin,
      intracranial artery dissection is reportedly more common in children and in Asian
      populations. Risk factors and mechanisms are poorly understood, and diagnosis is
      challenging because characteristic imaging features can be difficult to detect in
      view of the small size of intracranial arteries. Therefore, multimodal follow-up
      imaging is often needed to confirm the diagnosis. Treatment of intracranial
      artery dissections is empirical in the absence of data from randomised controlled
      trials. Most patients with subarachnoid haemorrhage undergo surgical or
      endovascular treatment to prevent rebleeding, whereas patients with intracranial
      artery dissection and cerebral ischaemia are treated with antithrombotics.
      Prognosis seems worse in patients with subarachnoid haemorrhage than in those
      without. 

PMID- 25987286
TI  - Static, dynamic and inoculum augmented respiration based test assessment for
      determining in-vessel compost stability.
AB  - The purpose of this work was to evaluate compost (and related industry) stability
      tests given recent large-scale changes to feedstock, processing techniques and
      compost market requirements. Five stability tests (ORG0020, DR4, Dewar self
      heating, oxygen update rate (OUR) and static respiration) were evaluated on
      composts from ten in-vessel composting sites. Spearman rank correlation
      coefficients were strong for the ORG0020, OUR and DR4 (both CO2 and O2
      measurement), however, OUR results required data extrapolation for highly active
      compost samples. By comparison the Dewar self-heating and static respiration
      tests had weaker correlations, in part the result of under reporting highly
      active, low pH samples. The findings suggest that despite differences in pre
      incubation period both dynamic respiration tests (ORG0020 and DR4) are best
      suited to deal with the wide range of compost stabilities found. 

PMID- 25987285
TI  - Relationship between respiratory quotient, nitrification, and nitrous oxide
      emissions in a forced aerated composting process.
AB  - We assessed the relationship between respiratory quotient (RQ) and nitrification
      and nitrous oxide (N2O) emission in forced aerated composting using lab-scale
      reactors. Relatively high RQ values from degradation of readily degradable
      organics initially occurred. RQ then stabilized at slightly lower values, then
      decreased. Continuous emission of N2O was observed during the RQ decrease.
      Correlation between nitrification and N2O emission shows that the latter was
      triggered by nitrification. Mass balances demonstrated that the O2 consumption of
      nitrification (~24.8mmol) was slightly higher than that of CO2 emission
      (~20.0mmol), indicating that the RQ decrease was caused by the occurrence of
      nitrification. Results indicate that RQ is a useful index, which not only
      reflects the bioavailability of organics but also predicts the occurrence of
      nitrification and N2O emission in forced aerated composting. 

PMID- 25987287
TI  - Anaerobic digestion of food waste using yeast.
AB  - Fermentative breakdown of food waste seems a plausible alternative to feeding
      food waste to pigs, incineration or garbage disposal in tourist areas. We
      determined the optimal conditions for the fermentative breakdown of food waste
      using yeast (Saccharomyces cerevisiae) in incubations up to 30days. Yeast
      efficiently broke down food waste with food waste loadings as high as 700g FW/l.
      The optimum inoculation was ~46*10(6)cells/l of culture with a 40 degrees C
      optimum (25-40 degrees C). COD and BOD were reduced by ~30-50%. Yeast used
      practically all the available sugars and reduced proteins and lipids by ~50%.
      Yeast was able to metabolize lipids much better than expected. Starch was
      mobilized after very long term incubations (>20days). Yeast was effective in
      breaking down the organic components of food waste but CO2 gas and ethanol
      production (~1.5%) were only significant during the first 7days of incubations. 

PMID- 25987288
TI  - Determination of the optimal area of waste incineration in a rotary kiln using a
      simulation model.
AB  - The article presents a mathematical model to determine the flux of incinerated
      waste in terms of its calorific values. The model is applicable in waste
      incineration systems equipped with rotary kilns. It is based on the known and
      proven energy flux balances and equations that describe the specific losses of
      energy flux while considering the specificity of waste incineration systems. The
      model is universal as it can be used both for the analysis and testing of systems
      burning different types of waste (municipal, medical, animal, etc.) and for
      allowing the use of any kind of additional fuel. Types of waste incinerated and
      additional fuel are identified by a determination of their elemental composition.
      The computational model has been verified in three existing industrial-scale
      plants. Each system incinerated a different type of waste. Each waste type was
      selected in terms of a different calorific value. This allowed the full
      verification of the model. Therefore the model can be used to optimize the
      operation of waste incineration system both at the design stage and during its
      lifetime. 

PMID- 25987289
TI  - Epiphytic lichens as indicators of environmental quality around a municipal solid
      waste landfill (C Italy).
AB  - Epiphytic lichens have been used as indicators of environmental quality around a
      municipal solid waste landfill in C Italy. An integrated approach, using the
      diversity of epiphytic lichens, as well as element bioaccumulation and
      physiological parameters in the lichen Flavoparmelia caperata (L.) Hale was
      applied along a transect from the facility. The results highlighted the
      biological effects of air pollution around the landfill. The Index of Lichen
      Diversity (ILD) increased and the content of heavy metals (Cr, Cd, Cu, Fe, Ni and
      Zn) decreased with distance from the landfill. Clear stress signals were observed
      in lichens growing in front of the facility, i.e. discoloration, necrosis,
      membrane lipid peroxidation, lower ergosterol content, higher dehydrogenase
      activity. Decreased photosynthetic efficiency, altered chlorophyll integrity and
      production of secondary metabolites were also found. The results suggested that
      lichens can be profitably used as bioindicators of environmental quality around
      landfills. 

PMID- 25987290
TI  - On-line monitoring of airborne bioaerosols released from a composting/green waste
      site.
AB  - This study is the first to employ the on-line WIBS-4 (Wideband Integrated
      Bioaerosol Sensor) technique for the monitoring of bioaerosol emissions and non
      fluorescing "dust" released from a composting/green waste site. The purpose of
      the research was to provide a "proof of principle" for using WIBS to monitor such
      a location continually over days and nights in order to construct comparative
      "bioaerosol site profiles". The real-time data obtained was then used to assess
      variations of the bioaerosol counts as a function of size, "shape", site
      location, working activity levels, time of day, relative humidity, wind speeds
      and wind directions. Three short campaigns were undertaken, one classified as a
      "light" workload period, another as a "heavy" workload period and finally a
      weekend when the site was closed. One main bioaerosol size regime was found to
      predominate: 0.5-3MUm with morphologies ranging from elongated to
      ellipsoidal/spherical. The real-time number-concentration data provides a long
      term "video" record of the site and were consistent with the Andersen sampling
      protocol performed that provides only a single "snapshot" for bioaerosol release.
      The number-concentration of fluorescent particles as a proportion of total
      particle counts amounted, on average, to ~1% for the "light" workday period, ~7%
      for the "heavy" workday period and ~18% for the weekend. The bioaerosol release
      profiles at the weekend were considerably different from those monitored during
      the working weekdays. 

PMID- 25987291
TI  - A ready-to-use, versatile, multiplex-able three-dimensional scaffold-based
      immunoassay chip for high throughput hepatotoxicity evaluation.
AB  - Hydrogel as three-dimensional (3D) substrate has been employed in miniaturized
      high throughput protein detection platforms to increase the number of effective
      antibodies and signal augmentation. However, the high water content of the
      hydrogel can dilute samples and create barrier to mass transfer, limiting
      hydrogel height to several microns in most platforms. Moreover, these platforms
      cannot achieve widespread use in common laboratories as they usually rely heavily
      on expensive robotic liquid handlers and custom-built components. Here we
      developed a ready-to-use, easy to store and handle, versatile and multiplex-able
      3D scaffold-based immunoassay chip (3D immunoChip) possible for high throughput
      protein quantification using bench-top equipment in common laboratories. Sample
      dilution, mass transfer, signal scattering and storage problems can be avoided by
      using dry scaffolds that regain transparency upon rehydration. When combined with
      hydrophilic-hydrophobic patterned reagent loading slides, manual high throughput
      handling of samples can be achieved. As these micro-scaffolds are patterned
      without barriers in between, simultaneous and effortless washing of all the
      reaction zones is possible in a Petri dish. Such features aid the 3D immunoChip
      in saving up to 100 times reagent and about 6 times labour. The 3D immunoChip is
      able to detect albumin (ALB), as a model analyte, from 5 ng mL(-1) to 1000 ng mL(
      1), making it comparable to the commercialized ELISA kit based on a 96-well plate
      (0.22-400 ng mL(-1)). This thus enables the 3D immunoChip to directly detect ALB
      secreted by HepaRG cells cultured in a 3D cell culture array chip for high
      throughput drug hepatotoxicity evaluation, which could potentially accelerate
      drug screening. 

PMID- 25987292
TI  - Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3
      oxidosqualene to supernatant protein factor.
AB  - We present the crystal structures of the SEC14-like domain of supernatant protein
      factor (SPF) in complex with squalene and 2,3-oxidosqualene. The structures were
      resolved at 1.75A (complex with squalene) and 1.6A resolution (complex with 2,3
      oxidosqualene), leading in both cases to clear images of the protein/substrate
      interactions. Ligand binding is facilitated by removal of the Golgi-dynamics
      (GOLD) C-terminal domain of SPF, which, as shown in previous structures of the
      apo-protein, blocked the opening of the binding pocket to the exterior. Both
      substrates bind into a large hydrophobic cavity, typical of such lipid
      transporter family. Our structures report no specific recognition mode for the
      epoxide group. In fact, for both molecules, ligand affinity is dominated by
      hydrophobic interactions, and independent investigations by computational models
      or differential scanning micro-calorimetry reveal similar binding affinities for
      both ligands. Our findings elucidate the molecular bases of the role of SPF in
      sterol endo-synthesis, supporting the original hypothesis that SPF is a
      facilitator of substrate flow within the sterol synthetic pathway. Moreover, our
      results suggest that the GOLD domain acts as a regulator, as its conformational
      displacement must occur to favor ligand binding and release during the different
      synthetic steps. 

PMID- 25987293
TI  - Early mobilization in the critical care unit: A review of adult and pediatric
      literature.
AB  - Early mobilization of critically ill patients is beneficial, suggesting that it
      should be incorporated into daily clinical practice. Early passive, active, and
      combined progressive mobilizations can be safely initiated in intensive care
      units (ICUs). Adult patients receiving early mobilization have fewer ventilator
      dependent days, shorter ICU and hospital stays, and better functional outcomes.
      Pediatric ICU data are limited, but recent studies also suggest that early
      mobilization is achievable without increasing patient risk. In this review, we
      provide a current and comprehensive appraisal of ICU mobilization techniques in
      both adult and pediatric critically ill patients. Contraindications and perceived
      barriers to early mobilization, including cost and health care provider views,
      are identified. Methods of overcoming barriers to early mobilization and
      enhancing sustainability of mobilization programs are discussed. Optimization of
      patient outcomes will require further studies on mobilization timing and
      intensity, particularly within specific ICU populations. 

PMID- 25987294
TI  - Towards core outcome set (COS) development: a follow-up descriptive survey of
      outcomes in Cochrane reviews.
AB  - BACKGROUND: A core outcome set (COS) can address problems of outcome
      heterogeneity and outcome reporting bias in trials and systematic reviews,
      including Cochrane reviews, helping to reduce waste. One of the aims of the
      international Core Outcome Measures in Effectiveness Trials (COMET) Initiative is
      to link the development and use of COS with the outcomes specified and reported
      in Cochrane reviews, including the outcomes listed in the summary of findings
      (SoF) tables. As part of this work, an earlier exploratory survey of the outcomes
      of newly published 2007 and 2011 Cochrane reviews was performed. This survey
      examined the use of COS, the variety of specified outcomes, and outcome reporting
      in Cochrane reviews by Cochrane Review Group (CRG). To examine changes over time
      and to explore outcomes that were repeatedly specified over time in Cochrane
      reviews by CRG, we conducted a follow-up survey of outcomes in 2013 Cochrane
      reviews. METHODS: A descriptive survey of outcomes in Cochrane reviews that were
      first published in 2013. Outcomes specified in the methods sections and reported
      in the results section of the Cochrane reviews were examined by CRG. We also
      explored the uptake of SoF tables, the number of outcomes included in these, and
      the quality of the evidence for the outcomes. RESULTS: Across the 50 CRGs, 375
      Cochrane reviews that included at least one study specified a total of 3142
      outcomes. Of these outcomes, 32 % (1008) were not reported in the results section
      of these reviews. For 23 % (233) of these non-reported outcomes, we did not find
      any reason in the text of the review for this non-report. Fifty-seven percent
      (216/375) of reviews included a SoF table. CONCLUSIONS: The proportion of
      specified outcomes that were reported in Cochrane reviews had increased in 2013
      (68 %) compared to 2007 (61 %) and 2011 (65 %). Importantly, 2013 Cochrane
      reviews that did not report specified outcomes were twice as likely to provide an
      explanation for why the outcome was not reported. There has been an increased
      uptake of SoF tables in Cochrane reviews. Outcomes that were repeatedly specified
      in Cochrane reviews by CRG in 2007, 2011, and 2013 may assist COS development.

PMID- 25987295
TI  - Expression and function of purinergic P2Y12 receptors in rat trigeminal ganglion
      neurons.
AB  - Purinergic receptors play key signaling roles in neuropathic pain in the
      orofacial region, which is innervated by trigeminal ganglion (TG) neurons. The
      neuropathology of purinergic P2Y12 receptors is well characterized in glia;
      however, their physiological role in TG neurons remains to be fully elucidated.
      The present study investigated the expression and function of P2Y12 receptors in
      rat TG neurons. P2Y12 receptor immunoreactivity was intense in the soma,
      dendrites, and axons, and colocalized with a pan-neuronal marker, neurofilament
      H, isolectin B4, and substance P. In the presence of extracellular Ca(2+), 2
      methylthio-ADP (an agonist of P2Y1, 12, 13 receptors) transiently increased
      intracellular free Ca(2+) concentrations ([Ca(2+)]i), an effect that was
      abolished by P2Y12 receptor antagonists. In the absence of extracellular Ca(2+),
      ryanodine receptor/channel inhibitors diminished the 2-methylthio-ADP-induced
      increases in [Ca(2+)]i. A sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor
      gradually increased [Ca(2+)]i, and after a plateau, application of 2-MeS-ADP
      induced a rapid and transient, but additive increase in [Ca(2+)]i. An adenylate
      cyclase inhibitor transiently increased [Ca(2+)]i, while a phosphodiesterase
      inhibitor prevented the 2-methylthio-ADP-induced increase in [Ca(2+)]i. Our study
      shows that P2Y12 receptors are expressed in TG neurons, and act via a cAMP
      dependent pathway to release intracellular Ca(2+) from ryanodine-sensitive Ca(2+)
      stores. 

PMID- 25987296
TI  - Economic evaluation of single-pill combination of indapamide and amlodipine in
      the treatment of arterial hypertension in the Polish setting.
AB  - BACKGROUND: Arterial hypertension is a common disorder that affects around 9
      million adults in Poland. Single-pill combinations (SPCs) for the treatment of
      arterial hypertension have significant advantages over the free combinations,
      resulting in lower risk of cardiovascular events and lower consumption of medical
      resources. The current ESC/ESH 2013 guidelines for the first time recommend
      treatment with a combination of thiazide-like diuretic with calcium channel
      blocker. Currently, no such combination is reimbursed from public funds in
      Poland. AIM: To assess the economic value of treatment with SPC of indapamide and
      amlodipine (Tertens-AM(r)) for hypertensive patients compared with free
      combination therapy (FC), in the Polish setting. METHODS: As there are currently
      no published data directly estimating the additional effect of using indapamide +
      amlo-dipine SPC vs. FC, two extreme approaches are presented: with difference in
      effectiveness due to improved adherence to the treatment estimated from published
      studies on other molecules used in hypertension such as SPCs and FCs - the base
      case approach (1); and assuming no difference of effectiveness or adherence
      between SPC and FC of indapamide and amlodipine - the conservative approach (2).
      Modelling was carried out based on the Markov process in lifetime horizon. In the
      base-case approach, with the difference in effectiveness between SPC and FC, it
      was assumed that the differences in compliance translate into the differences in
      systolic blood pressure. Patients' characteristics were correlated with the risk
      of events associated with cardiovascular disease, based on the prediction
      algorithms from the Framingham Heart Study. Costs were considered from a National
      Health Fund (NHF) perspective and NHF and patient's perspective, and therefore
      direct medical costs were only included. RESULTS: The treatment with SPC of
      indapamide and amlodipine in place of FC resulted in 7.6 additional days of life
      in full health and longer overall patient survival by 2.9 days. The replacement
      of FC with SPC would result in national savings from both NHF perspective and NHF
      and patient's perspective, irrespective of the assumption of the difference in
      adherence between SPC and FC. The savings would amount to 1.602-3.954 million PLN
      and 16.498-19.186 million PLN from NHF perspective and NHF and patient's
      perspective, respectively. CONCLUSIONS: The treatment with SPC of indapamide and
      amlodipine for hypertensive patients was found to be dominant over FC or at least
      less expensive than treatment with FC when the difference in effectiveness was
      neglected. The replacement of FC with SPC would result in savings from both NHF
      perspective and NHF and patient's perspective.

PMID- 25987297
TI  - Epithelial and stromal alterations in prostate after cypermethrin administration
      in adult albino rats (histological and biochemical study).
AB  - Histological and biochemical alterations induced in prostate by cypermethrin
      insecticide exposure were investigated in adult albino rats. 60 mg/kg/day of
      cypermethrin were given orally to experimental group for 15 days then prostatic
      specimens were processed for light and electron microscopic examinations and for
      assessment of oxidative stress markers; prostatic glutathione (GSH), glutathione
      peroxidase enzyme (GPx) and malondialdehyde (MDA). Masson's trichrome and anti
      alpha-actin antibodies immunohistochemical staining were done. Blood samples were
      collected for measurement of total and prostatic acid phosphatase enzymes.
      Morphometric and statistical analyses were conducted. Cypermethrin treated group
      showed decrease in acinar epithelial height with detection of heterochromatic
      nuclei, cytoplasmic vacuolations and few apical microvilli. The stroma
      surrounding the acini was widened with significant increase in collagen fibers
      and significant decrease in smooth muscle cell alpha-actin immunoexpression. This
      was accompanied by a significant decrease of prostatic GSH level, activity of GPx
      enzyme with a significant increase in MDA level. Significant decrease in total
      and prostatic enzyme activities was also detected. In conclusion, cypermethrin
      induced epithelial degenerative changes in prostate which were accompanied by
      stromal alterations that seemed to be due to oxidative stress. More attention is
      required to the role of stromal microenvironment and oxidative stress markers in
      prostatic diseases.

PMID- 25987298
TI  - Qualitative Exploration of an Effective Depression Literacy Fotonovela with at
      Risk Latina Immigrants.
AB  - While depression is prevalent among immigrant Latinas, mental health literacy is
      low. Culturally tailored health narratives can improve mental health literacy and
      are now increasingly featured in Spanish language fotonovelas (i.e., booklets in
      a comic book format with posed photographs and dialogue bubbles). The purpose of
      this qualitative study is to explore why a depression literacy fotonovela proved
      effective with Latina immigrants at risk for depression in a quantitative
      randomized control study. This study is the qualitative companion of the
      previously published quantitative piece of a mixed methods study, the latter
      revealing posttest improvements in depression knowledge, self-efficacy to
      identify the need for treatment, and decreased stigma towards mental health care
      (Hernandez and Organista in Am J Community Psychol 2013. doi: 10.1007/s10464-013
      9587-1 ). Twenty-five immigrant Latinas participated in structured interviews, in
      the current qualitative study, 3 weeks after participating in the quantitative
      study. Results suggest depression literacy improved because participants
      evidenced high recall of the storyline and characters, which they also found
      appealing (e.g., liked peer and professional support offered to depressed main
      character). Further, identification with the main character was reflected in
      participants recalling similar circumstances impacting their mental health.
      Despite some improvement, stigma related to depression and its treatment remained
      for some women. Future research for the improvement of health literacy tools is
      discussed. 

PMID- 25987299
TI  - Micro-solid-phase extraction of organochlorine pesticides using porous metal
      organic framework MIL-101 as sorbent.
AB  - In this study, a metal-organic framework material, MIL-101, used as a micro-solid
      phase extraction (MU-SPE) sorbent for efficient enrichment of five organochlorine
      pesticides (OCPs), including alpha-HCH, Aldrin, alpha-Chlordane, Dieldrin and
      p,p'-DDD from water samples, followed by gas chromatography-mass spectrometry, is
      reported. This study demonstrated a new application of MIL-101 using MU-SPE, an
      advantage of the latter being its ability to process complex aqueous matrices,
      due to the protection of the sorbent afforded by the hollow fiber membrane bag.
      Key factors affecting extraction efficiency were studied, including elution
      solvent, extraction and desorption time. Under the optimal extraction conditions,
      the calibration plots were linear from 0.05 to 50 ng/mL for alpha-HCH and p,p'
      DDD, and 0.1 to 50 ng/mL for the other three analytes. The limits of detection
      were between 0.0025 and 0.016 ng/mL. The relative recoveries of the OCPs spiked
      into real water samples (at 5 ng/mL of each analyte) ranged from 87.6 to 98.6%
      with relative standard deviations of <10%.

PMID- 25987300
TI  - Infertility in Inflammatory Bowel Diseases: A Cause for Hope?

PMID- 25987301
TI  - Evidence Against Routine Testing of Patients With Functional Gastrointestinal
      Disorders for Celiac Disease: A Population-based Study.
AB  - BACKGROUND & AIMS: Celiac disease has been linked to irritable bowel syndrome
      (IBS)-like symptoms in outpatient clinics. Guidelines recommend that all patients
      with IBS-like symptoms undergo serologic testing for celiac disease, but there is
      controversy over whether celiac disease is more prevalent in populations with IBS
      like symptoms. We aimed to determine whether positive results from serologic
      tests for celiac disease are associated with IBS and other functional
      gastrointestinal disorders (FGIDs) in a large U.S. white population. METHODS:
      Validated, self-report bowel disease questionnaires (BDQs) were sent to randomly
      selected cohorts of Olmsted County, Minnesota residents. In separate protocols,
      serum samples were collected from more than 47,000 Olmsted County residents
      without a prior diagnosis of celiac disease; we performed serologic tests for
      celiac disease on stored serum samples from residents who completed the BDQ.
      Logistic regression was used to test for the association between serologic
      markers of celiac disease (positive vs negative) and individual FGIDs. RESULTS: A
      total of 3202 subjects completed the BDQ and had serum available for testing. IBS
      was identified in 13.6% of these subjects (95% confidence interval [CI], 12.4%
      14.8%), and any gastrointestinal symptom occurred in 55.2% (95% CI, 53.5%-56.9%).
      The prevalence of celiac disease on the basis of serologic markers was 1.0% (95%
      CI, 0.7%-1.4%). IBS was less prevalent in patients with celiac disease (3%) than
      patients without celiac disease (14%), although the difference was not
      statistically significant (odds ratio, 0.2; 95% CI, 0.03-1.5). Abdominal pain,
      constipation, weight loss, and dyspepsia were the most frequent symptom groups in
      subjects who were seropositive for celiac disease, but none of the
      gastrointestinal symptoms or disorders were significantly associated with celiac
      disease serology. CONCLUSIONS: Symptoms indicative of FGIDs and seropositive
      celiac disease are relatively common in a U.S. white community. Testing for
      celiac disease in patients with IBS in the community may not have a significantly
      increased yield over population-based screening in the United States.

PMID- 25987302
TI  - Ecology and geographic distribution of Yersinia enterocolitica among livestock
      and wildlife in China.
AB  - The results in this study show the prevalence of Yersinia enterocolitica varies
      in different animal species and regions of China. The highest prevalence is among
      pigs (12.91%), followed by dogs (9.80%), Ochotona curzoniae (plateau pica)
      (6.76%), chickens (4.50%), rodents (3.40%), cattle (2.78%) and sheep (0.89%).
      Pathogenic isolates comprised the majority of the Y. enterocolitica recovered
      from pigs (73.50%) and dogs (59.44%); whereas the nonpathogenic Y. enterocolitica
      made up most of poultry and wildlife recovered strains. A correlation analysis
      comparing the prevalence and geographic factors showed the isolation rate of Y.
      enterocolitica in pigs and dogs was negatively correlated with elevation (r=
      0.50, P<0.05) and annual average air temperature (r=-0.43, P<0.05), but there was
      positive correlation with annual precipitation (r=0.43, P<0.05); conversely, the
      isolation rate from wildlife is positively correlated with elevation (r=0.3,
      P<0.05) contrary to the result seen in livestock. Twelve novel biotype 2
      pathogenic Y. enterocolitica carried ail and ystB virulence genes, and one
      biotype 1A nonpathogenic strain positive with ail, ystB and ystA genes were
      isolated from Microtus fuscus (Qinghai vole) on plague foci of the Qinghai-Xizang
      plateau. The PFGE pattern K6GN11C30021 was predominant in pigs (44.25%) and
      patients (41.18%); K6GN11C30068 was predominant in dogs (40.16%). Animal isolates
      from the same region shared the same pattern (K6GN11C30021 and K6GN11C30012),
      indicating they may be from the same clone and arose through cross infection.
      Moreover, the identical PFGE pattern among local animals and diarrhea patients
      suggested that the animals may be the source of infections in these areas. 

PMID- 25987303
TI  - Frequency of Faith and Spirituality Discussion in Health Care.
AB  - Faith and spirituality are important in the lives of many individuals, and
      therefore, many patients. This study was performed to determine whether faith and
      spirituality are active part of the healthcare field and patients' receipt of
      these sometimes delicate topics. The nuances of the concepts of faith,
      spirituality, and religion and their implications in the healthcare setting are
      discussed. Benefits and detriments of faith and spirituality are reviewed in
      terms of how they relate to the health of the patient and to the healthcare
      field. With the focus of healthcare shifting to holistic care, this conversation
      may be more necessary than ever in practice, yet it seems many providers are not
      discussing these matters with patients. The study analyzes whether healthcare
      providers are discussing these topics with patients and how the discussion is
      received or would be received by patients. Findings demonstrate the infrequency
      of the discussion regardless of the fact that the majority of patients consider
      themselves faithful or spiritual. This study was approved by the Clarkson
      University Institutional Review Board on June 18, 2104. 

PMID- 25987304
TI  - Color associations to emotion and emotion-laden words: A collection of norms for
      stimulus construction and selection.
AB  - Color has the ability to influence a variety of human behaviors, such as object
      recognition, the identification of facial expressions, and the ability to
      categorize stimuli as positive or negative. Researchers have started to examine
      the relationship between emotional words and colors, and the findings have
      revealed that brightness is often associated with positive emotional words and
      darkness with negative emotional words (e.g., Meier, Robinson, & Clore,
      Psychological Science, 15, 82-87, 2004). In addition, words such as anger and
      failure seem to be inherently associated with the color red (e.g., Kuhbandner &
      Pekrun). The purpose of the present study was to construct norms for positive and
      negative emotion and emotion-laden words and their color associations.
      Participants were asked to provide the first color that came to mind for a set of
      160 emotional items. The results revealed that the color RED was most commonly
      associated with negative emotion and emotion-laden words, whereas YELLOW and
      WHITE were associated with positive emotion and emotion-laden words,
      respectively. The present work provides researchers with a large database to aid
      in stimulus construction and selection.

PMID- 25987305
TI  - Conducting spoken word recognition research online: Validation and a new timing
      method.
AB  - Models of spoken word recognition typically make predictions that are then tested
      in the laboratory against the word recognition scores of human subjects (e.g.,
      Luce & Pisoni Ear and Hearing, 19, 1-36, 1998). Unfortunately, laboratory
      collection of large sets of word recognition data can be costly and time
      consuming. Due to the numerous advantages of online research in speed, cost, and
      participant diversity, some labs have begun to explore the use of online
      platforms such as Amazon's Mechanical Turk (AMT) to source participation and
      collect data (Buhrmester, Kwang, & Gosling Perspectives on Psychological Science,
      6, 3-5, 2011). Many classic findings in cognitive psychology have been
      successfully replicated online, including the Stroop effect, task-switching
      costs, and Simon and flanker interference (Crump, McDonnell, & Gureckis PLoS ONE,
      8, e57410, 2013). However, tasks requiring auditory stimulus delivery have not
      typically made use of AMT. In the present study, we evaluated the use of AMT for
      collecting spoken word identification and auditory lexical decision data.
      Although online users were faster and less accurate than participants in the lab,
      the results revealed strong correlations between the online and laboratory
      measures for both word identification accuracy and lexical decision speed. In
      addition, the scores obtained in the lab and online were equivalently correlated
      with factors that have been well established to predict word recognition,
      including word frequency and phonological neighborhood density. We also present
      and analyze a method for precise auditory reaction timing that is novel to
      behavioral research. Taken together, these findings suggest that AMT can be a
      viable alternative to the traditional laboratory setting as a source of
      participation for some spoken word recognition research.

PMID- 25987306
TI  - PsiMLE: A maximum-likelihood estimation approach to estimating psychophysical
      scaling and variability more reliably, efficiently, and flexibly.
AB  - A simple and popular psychophysical model-usually described as overlapping
      Gaussian tuning curves arranged along an ordered internal scale-is capable of
      accurately describing both human and nonhuman behavioral performance and neural
      coding in magnitude estimation, production, and reproduction tasks for most
      psychological dimensions (e.g., time, space, number, or brightness). This model
      traditionally includes two parameters that determine how a physical stimulus is
      transformed into a psychological magnitude: (1) an exponent that describes the
      compression or expansion of the physical signal into the relevant psychological
      scale (beta), and (2) an estimate of the amount of inherent variability (often
      called internal noise) in the Gaussian activations along the psychological scale
      (sigma). To date, linear slopes on log-log plots have traditionally been used to
      estimate beta, and a completely separate method of averaging coefficients of
      variance has been used to estimate sigma. We provide a respectful, yet critical,
      review of these traditional methods, and offer a tutorial on a maximum-likelihood
      estimation (MLE) and a Bayesian estimation method for estimating both beta and
      sigma [PsiMLE(beta,sigma)], coupled with free software that researchers can use
      to implement it without a background in MLE or Bayesian statistics (R-PsiMLE). We
      demonstrate the validity, reliability, efficiency, and flexibility of this method
      through a series of simulations and behavioral experiments, and find the new
      method to be superior to the traditional methods in all respects. 

PMID- 25987307
TI  - Molecular events in relapsed oral squamous cell carcinoma: Recurrence vs.
      secondary primary tumor.
AB  - Relapses have a great impact on both the morbidity and mortality rates of oral
      squamous cell carcinoma (OSCC) patients. Current classification criteria are
      imprecise and need improvements. Recent advances in understanding of OSCC
      relapses on a molecular level provide new possibilities to better classify true
      recurrences and second primary tumors. This review discusses the limitations of
      the current OSCC relapse classification method and presents possible alternatives
      to improve this classification based on molecular techniques. Moreover, these
      molecular techniques add to the further understanding of these lesions and may
      provide tools for clinical management. 

PMID- 25987308
TI  - Investigation of salivary free amino acid profile for early diagnosis of breast
      cancer with ultra performance liquid chromatography-mass spectrometry.
AB  - BACKGROUND: Breast cancer (BC) is the second leading cause of cancer death in
      women worldwide. This study aimed at investigating salivary free amino acid
      (SFAA) profile to facilitate the early diagnosis of BC. METHODS: Unstimulated
      whole saliva from BC patients (n=27) and randomly from healthy females (n=28)
      were assayed with ultra-performance liquid chromatography-mass spectrometry (UPLC
      MS). Receiver operating characteristic curve (ROC) was used to evaluate the
      diagnostic performance of each of the amino acid (AA) biomarkers, or SFAA profile
      index for BC screening. RESULTS: Concentrations of 15 SFAAs demonstrated
      significant differences (P<0.05) between BC patients at stages I-II and healthy
      controls (HC). The area under the curve (AUC) values in HC vs BCs I-II based on
      single AA were from 0.695 to 0.866. The AUC for SFAA profile index combined Pro,
      Thr, His was 0.916 (sensitivity 88.2%, specificity 85.7%) in distinguishing HC
      from BCs I-II. CONCLUSIONS: The diagnostic potentials of 15 SFAAs as early
      diagnostic biomarkers for BC were verified and the diagnostic accuracy was
      improved in the use of SFAA profile index. The detection of SFAA profile is
      expected to be applied for the preclinical screening of early stage of BC in the
      future.

PMID- 25987309
TI  - Derivation of gender and age-specific reference intervals from fully normal
      Japanese individuals and the implications for health screening.
AB  - BACKGROUND: With nationwide standardization of laboratory tests among
      institutions for health screening in Japan, common reference intervals (RIs) were
      derived from records of 1,500,000 health check attendees. METHODS: Targets were
      20 basic laboratory tests including body mass index (BMI) and systolic and
      diastolic blood pressures (SBP, DBP). Individuals fulfilling the following strict
      criteria were chosen: SBP<130, DBP<85mmHg, BMI<25kg/m(2), non-smoking, ethanol
      consumption<20g/day and under no mediation with no remarkable current/past
      illnesses. The latent abnormal values exclusion (LAVE) method was applied to
      ensure fully normal results. RIs were derived by parametric method using modified
      Box-Cox power transformation. RESULTS: Among all attendees, 23% fulfilled the
      criteria. Application of the LAVE method further reduced the dataset by 40%-50%.
      Age-related charts of test results differed greatly between genders in almost all
      tests. Comparison of derived RIs with clinical decision limits (CDLs) revealed
      that the upper limits of RIs differed from CDLs according to gender and age.
      CONCLUSIONS: Implementation of gender and age-specific RIs derived from
      individuals with fully normal health attributes will (1) enable appropriate
      interpretation of test results in health screening and (2) promote judicious
      application of CDLs for therapeutic intervention, taking into account gender, age
      and other health attributes.

PMID- 25987310
TI  - Antibody-mediated rejection is associated with impaired graft function in
      pediatric heart transplant recipients.

PMID- 25987311
TI  - Eosinophil count, allergies, and rejection in pediatric heart transplant
      recipients.
AB  - BACKGROUND: Allograft rejection and long-term immunosuppression remain
      significant challenges in pediatric heart transplantation. Pediatric recipients
      are known to have fewer rejection episodes and to develop more allergic
      conditions than adults. A T-helper 2 cell dominant phenotype, manifested
      clinically by allergies and an elevated eosinophil count, may be associated with
      immunologic quiescence in transplant recipients. This study assessed whether the
      longitudinal eosinophil count and an allergic phenotype were associated with
      freedom from rejection. METHODS: This single-center, longitudinal, observational
      study included 86 heart transplant patients monitored from 1994 to 2011. Post
      transplant biannual complete blood counts, allergic conditions, and clinical
      characteristics related to rejection risk were examined. RESULTS: At least 1
      episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody
      mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were
      diagnosed with an allergic condition. Patients with ACR or AMR had a lower
      eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022,
      respectively). In the multivariable regression analysis, the presence of panel
      reactive antibodies to human leukocyte antigen I (p = 0.014) and the median
      eosinophil count (p = 0.011) were the only independent covariates associated with
      AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent
      risk factors for ACR. Allergic conditions or young age at transplant were not
      protective from rejection. CONCLUSIONS: This study demonstrates a novel
      association between a high eosinophil count and freedom from rejection.
      Identifying a biomarker for low rejection risk may allow a reduction in
      immunosuppression. Further investigation into the role of the T-helper 2 cell
      phenotype and eosinophils in rejection quiescence is warranted.

PMID- 25987312
TI  - Global left ventricular relaxation: A novel tissue Doppler index of acute
      rejection in pediatric heart transplantation.
AB  - BACKGROUND: Serial invasive cardiac catheterization with endomyocardial biopsies
      (EMBs) is the current standard of reference for evaluation after orthotopic heart
      transplant (OHTx). We developed a novel, non-invasive echocardiographic index of
      global left ventricular relaxation (LVRI) and assessed its sensitivity,
      specificity and predictive value for detecting rejection compared with EMB
      results in a prospective study conducted from September 2012 through May 2014.
      METHODS: LVRI was calculated as the sum of diastolic tissue Doppler imaging (TDI)
      velocities (E') of the left ventricular lateral, septal and posterior walls
      divided by the percentage of left ventricular posterior wall (LVPW) thinning by M
      mode. LVRI was measured in 47 OHTx patients and 50 patients with normal hearts.
      Of the 33 patients who underwent clinically indicated EMB, 22 patients had Grade
      0R EMB, 6 had Grade 1R and 5 had Grade 2R to 3R biopsy results. Sensitivity,
      specificity and predictive value of LVRI for discriminating Grade 1R to 3R EMB
      were calculated. The LVRI was compared before and after OHTx rejection treatment
      and during the early and late post-transplant period. To characterize LVRI, 1-way
      analysis of variance was used to compare all groups, including non-OHTx patients.
      RESULTS: LVRI was lower in patients with Grade 0R EMBs compared with non-OHTx
      patients. Patients with Grade 1R to 3R EMBs had lower LVRI than those with Grade
      0R EMBs. LVRI recovered after treatment for rejection. LVRI appeared to normalize
      between 40 and 90 days post-transplantation. After 90 days, sensitivity was 100%
      and specificity was 90.9% for detecting patients with Grade 1R to 3R EMBs using
      an LVRI of 0.8. CONCLUSION: LVRI, a novel, non-invasive TDI index of global left
      ventricular diastolic dysfunction, appears to be useful for detecting rejection
      in children beyond 3 months post-OHTx.

PMID- 25987313
TI  - Fontan-associated protein-losing enteropathy and heart transplant: A Pediatric
      Heart Transplant Study analysis.
AB  - BACKGROUND: Post-Fontan protein-losing enteropathy (PLE) is associated with
      significant morbidity and mortality. Although heart transplantation (HTx) can be
      curative, PLE may increase the risk of morbidity before and after HTx. This study
      analyzed the influence of PLE influence on waiting list and post-HTx outcomes in
      a pediatric cohort. METHODS: Fontan patients listed for HTx and enrolled in the
      Pediatric Heart Transplant Study from 1999 to 2012 were stratified by a diagnosis
      of PLE, and the association of PLE with waiting list and post-HTx mortality,
      rejection, and infection was analyzed. RESULTS: Compared with non-PLE Fontan
      patients (n = 260), PLE patients listed for HTx (n = 96) were older (11.9 years
      vs 7.6 years; p = 0.003), had a larger body surface area (1.1 m(2) vs 0.9 m(2); p
      = 0.0001), had lower serum bilirubin (0.5 vs 0.9 mg/dl; p = 0.01), lower B-type
      natriuretic peptide (59 vs 227 pg/ml; p = 0.006), and were less likely to be on a
      ventilator (3% vs 13%; p = 0.006). PLE patients had lower waiting list mortality
      than non-PLE Fontan patients (p < 0.0001). There were no intergroup differences
      for post-HTx survival or times to the first infection or rejection. PLE was not
      independently associated with increased post-HTx mortality at any time point.
      CONCLUSIONS: In this multicenter cohort, the diagnosis of PLE alone was not
      associated with increased waiting list mortality or post-HTx morbidity or
      mortality. Given the limitations of our data, this analysis suggests that PLE
      patients in the pediatric age group have outcomes similar to their non-PLE
      counterparts. Additional multicenter studies of PLE patients with targeted
      collection of PLE-specific information will be necessary to fully delineate the
      risks conferred by PLE for HTx.

PMID- 25987314
TI  - Functional characterization of PhGR and PhGRL1 during flower senescence in the
      petunia.
AB  - KEY MESSAGE: Petunia PhGRL1 suppression accelerated flower senescence and
      increased the expression of the genes downstream of ethylene signaling, whereas
      PhGR suppression did not. Ethylene plays an important role in flowers senescence.
      Homologous proteins Green-Ripe and Reversion to Ethylene sensitivity1 are
      positive regulators of ethylene responses in tomato and Arabidopsis,
      respectively. The petunia flower has served as a model for the study of ethylene
      response during senescence. In this study, petunia PhGR and PhGRL1 expression was
      analyzed in different organs, throughout floral senescence, and after exogenous
      ethylene treatment; and the roles of PhGR and PhGRL1 during petunia flower
      senescence were investigated. PhGRL1 suppression mediated by virus-induced gene
      silencing accelerated flower senescence and increased ethylene production;
      however, the suppression of PhGR did not. Taken together, these data suggest that
      PhGRL1 is involved in negative regulation of flower senescence, possibly via
      ethylene production inhibition and consequently reduced ethylene signaling
      activation.

PMID- 25987316
TI  - Post-repolarization refractoriness increases vulnerability to block and
      initiation of reentrant impulses in heterogeneous infarcted myocardium.
AB  - Myocardial infarction causes remodeling of the tissue structure and the density
      and kinetics of several ion channels in the cell membrane. Heterogeneities in
      refractory period (ERP) have been shown to occur in the infarct border zone and
      have been proposed to lead to initiation of arrhythmias. The purpose of this
      study is to quantify the window of vulnerability (WV) to block and initiation of
      reentrant impulses in myocardium with ERP heterogeneities using computer
      simulations. We found that ERP transitions at the border between normal
      ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions
      between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP
      transitions is a combination of electrotonic interaction between NZ and IZ cells
      and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP
      heterogeneities between NZ and IZ cells are more vulnerable to block and
      initiation of reentrant impulses than ERP heterogeneities between NZ cells. The
      relationship between coupling intervals of premature impulses (V1V2) and coupling
      intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and
      NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature
      impulses the shorter the coupling interval between the premature and first
      reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship
      measured during initiation of reentrant impulses in canine infarcted hearts which
      is direct. IN CONCLUSION: (1) ERP transitions at the NZ-IZ border are abrupt as a
      consequence of PRR; (2) PRR increases the vulnerability to block and initiation
      of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships
      measured at ERP heterogeneities in the computer model and in experimental canine
      infarcts are not consistent. Therefore, it is likely that other mechanisms like
      micro and/or macro structural heterogeneities also contribute to initiation of
      reentrant impulses in infarcted hearts.

PMID- 25987317
TI  - Development of a mobbing short scale in the Gutenberg Health Study.
AB  - PURPOSE: Despite its highly detrimental potential, most standard questionnaires
      assessing psychosocial stress at work do not include mobbing as a risk factor. In
      the German standard version of COPSOQ, mobbing is assessed with a single item. In
      the Gutenberg Health Study, this version was used together with a newly developed
      short scale based on the Leymann Inventory of Psychological Terror. The purpose
      of the present study was to evaluate the psychometric properties of these two
      measures, to compare them and to test their differential impact on relevant
      outcome parameters. METHODS: This analysis is based on a population-based sample
      of 1441 employees participating in the Gutenberg Health Study. Exploratory and
      confirmatory factor analyses and reliability analyses were used to assess the
      mobbing scale. To determine their predictive validities, multiple linear
      regression analyses with six outcome parameters and log-binomial regression
      models for two of the outcome aspects were run. RESULTS: Factor analyses of the
      five-item scale confirmed a one-factor solution, reliability was alpha = 0.65.
      Both the single-item and the five-item scales were associated with all six
      outcome scales. Effect sizes were similar for both mobbing measures. CONCLUSION:
      Mobbing is an important risk factor for health-related outcomes. For the purpose
      of psychosocial risk assessment in the workplace, both the single-item and the
      five-item constructs were psychometrically appropriate. Associations with
      outcomes were about equivalent. However, the single item has the advantage of
      parsimony, whereas the five-item construct depicts several distinct forms of
      mobbing.

PMID- 25987315
TI  - Molecular characterization of HbCZF1, a Hevea brasiliensis CCCH-type zinc finger
      protein that regulates hmg1.
AB  - KEY MESSAGE: The HbCZF1 protein binds to the hmg1 promoter in yeast and this
      interaction was confirmed in vitro. The hmg1 promoter was activated in transgenic
      plants by HbCZF1. Biosynthesis of natural rubber is known to be based on the
      mevalonate pathway in Hevea brasiliensis. The final step in the mevalonate
      production is catalyzed by the branch point enzyme, 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase (HMGR), which shunts HMG-CoA into the isoprenoid pathway,
      leading to the synthesis of natural rubber. However, molecular regulation of HMGR
      expression is not known. To study the transcriptional regulation of HMGR, the
      yeast one-hybrid experiment was performed to screen the latex cDNA library using
      the hmg1 (one of the three HMGR in H. brasiliensis) promoter as bait. One cDNA
      that encodes the CCCH-type zinc finger protein, designated as HbCZF1, was
      isolated from H. brasiliensis. HbCZF1 interacted with the hmg1 promoter in yeast
      one-hybrid system and in vitro. HbCZF1 contains a 1110 bp open reading frame that
      encodes 369 amino acids. The deduced HbCZF1 protein was predicted to possess a
      typical C-X7-C-X5-C3-H CCCH motif and RNA recognition motif. HbCZF1 was
      predominant in the latex, but little expression was detected in the leaves,
      barks, and roots. Furthermore, in transgenic tobacco plants, over-expression of
      HbCZF1 highly activated the hmg1 promoter. These results suggested that HbCZF1
      may participate in the regulation of natural rubber biosynthesis in H.
      brasiliensis.

PMID- 25987319
TI  - Ellagitannins, gallotannins, and gallo-ellagitannins from the galls of Tamarix
      aphylla.
AB  - Chromatographic separation of an aqueous acetone extract of the galls from
      Tamarix aphylla using gels resulted in isolation of an ellagitannin, phyllagallin
      M1 (13), a gallo-ellagitannin, phyllagallin D1 (14), and four gallotannins,
      phyllagallin M2 (15) and phyllagallins D2-D4 (16-18), in addition to four known
      ellagitannins and three phenolics of lower molecular weight structurally related
      to hydrolyzable tannins. The structures of the six new tannins were elucidated
      based on spectroscopic and chemical data. Among the phenolics, flavogallonic acid
      dilactone (8), which is presumed to be biogenetically produced by C-C oxidative
      coupling of an ellagic acid unit with a galloyl residue, shows an exceptional
      oxidative pattern of gallic acid residues in plants of the family Tamaricaceae.
      Although the ellagitannin tamarixellagic acid (4) was reported to be a
      constituent of the galls of T. aphylla, such compounds with anomalous location of
      the DHDG moiety at O-3 on the glucopyranose core have not been observed among the
      tannins of tamaricaceous plants. 

PMID- 25987318
TI  - New cytotoxic 19-norbufadienolide and bufogargarizin isolated from Chan Su.
AB  - One new 19-norbufadienolide (1) and one new bufogargarizin (2), together with
      twelve known bufadienolides (3-14, resp.) were isolated from Chan Su, a
      traditional Chinese medicine that is used in the treatment of cancer. Their
      structures were elucidated on the basis of detailed spectroscopic analysis and
      comparison of corresponding data that is previously reported. The cytotoxic
      activities of the isolated compounds were evaluated on HeLa and A549 cell lines.
      Though 1 and 2 showed weak cytotoxic activities on both cell lines, compounds 4
      and 5 showed lower IC50 values than bufalin, the most widely studied
      bufadienolide in Chan Su. Furthermore, four 3-ester derivatives (15-18) of
      compound 4 were synthesized and their cytotoxic activities were also evaluated.
      Analysis of the structure-activity relationship indicated that bufadienolides
      with aldehyde group at C-10 or alpha-hydroxyl group at C-11 exhibit stronger
      cytotoxic activities on both cell lines. The cytotoxic activity of arenobufagin-3
      ester derivative 17 was 4-fold higher than compound 4. 

PMID- 25987320
TI  - Phenylpropanoids and neolignans from Smilax trinervula.
AB  - A new phenylpropanoid glucoside and two new neolignans, namely (1S, 2R)-1-(3, 4,
      5-trimethoxyphenyl)-3-(beta-d-glucopyranosyloxy)-1, 2, 3-propanetriol (1), and
      (7R, 8R)-4, 7, 9, 9'-tetrahydroxy-3, 5, 3', 5'-tetramethoxy-8-4'-oxyneolignan 4-O
      beta-d-glucopyranoside (2) and 3', 9, 9'-trihydroxy-3, 5-dimethoxy-8-O-4'
      neolignan-4-O-beta-d-glucopyranoside (3), together with a new natural product
      (1S, 2R)-1-(3, 4, 5-trimethoxyphenyl)-1, 2, 3-propanetriol (4) and four known
      compounds (5-8) were isolated from the rhizomes of Smilax trinervula. Their
      structures were established mainly on the basis of 1D and 2D NMR spectral data,
      ESI-MS and literature comparisons. Compounds 1-8 were tested in vitro for their
      cytotoxic activities against 5 human tumor cell lines (SH-SY5Y, SGC-7901, HCT
      116, Lovo and Vero). Compounds 7 and 8 exhibited cytotoxic activity against Lovo,
      with IC50 values of 18.7MUM and 16.8MUM, respectively. 

PMID- 25987322
TI  - The anthracycline-trastuzumab interaction: a lesson in not jumping to confusion.

PMID- 25987321
TI  - Brasilane sesquiterpenoids and alkane derivatives from cultures of the
      basidiomycete Coltricia sideroides.
AB  - Three new brasilane-type sesquiterpenoids, brasilanes A-C (1-3), together with
      two new alkane derivatives, colisiderin A (4) and 7(E),9(E)-undecandiene-2,4,5
      triol (5), were isolated from cultures of the basidiomycete Coltricia sideroides.
      Their structures were elucidated by NMR and MS data analyses. The absolute
      configuration of 4 was determined by TDDFT ECD calculations while brasilane-type
      sesquiterpenoids were isolated from cultures of mushroom for the first time.
      Compounds 2 and 4 showed weak cytotoxicities against HL-60 and SW480,
      respectively. 

PMID- 25987323
TI  - Types of adult attention-deficit hyperactivity disorder (ADHD): baseline
      characteristics, initial response, and long-term response to treatment with
      methylphenidate.
AB  - Much recent research describes the importance of emotional symptoms in ADHD.
      While there is no accepted system for including emotionality in diagnosing ADHD,
      the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) provides a
      tool to facilitate this. It assesses a range of adult ADHD symptoms which load on
      two factors: inattentive and emotional dysregulation. The consistently high
      inattentive factor was used to define significant elevation on the more variable
      emotional dysregulation factor (which contains four WRAADDS domains:
      hyperactivity/restlessness, temper, affective lability, and emotional over
      reactivity) allowing the definition of two ADHD diagnostic types. We compared
      these two types on a broad range of adult subject characteristics, including
      response to methylphenidate (MPH) treatment assessed during two clinical trials.
      Marked impairment in three of the four emotional domains reflected a symptom
      severity level equivalent to that of the inattentive factor. 59 % met this
      threshold, defining them as ADHD emotion dysregulation presentation, as opposed
      to 41 % with ADHD inattentive presentation. Cluster analysis validated these
      groups by generating similar clusters with 85 % agreement regarding membership.
      ADHD emotional dysregulation presentation subjects showed more childhood ADHD
      symptoms, adult symptoms of oppositional defiant disorder, and evidence of
      personality disorder. Both types showed similar improvement during the double
      blind MPH arm of the trials and during a 6-month open-label phase. Based on the
      presence of symptoms of emotional dysregulation, ADHD in adults can be
      conceptualized as two types. Impairment and comorbidity in adults with ADHD are
      largely concentrated in ADHD emotional dysregulation presentation patients.

PMID- 25987324
TI  - The efficacy and safety of combined pulsed and conventional radiofrequency
      treatment of refractory cases of idiopathic trigeminal neuralgia: a retrospective
      study.
AB  - PURPOSE: We conducted a retrospective study to evaluate the efficacy and duration
      of pain relief for idiopathic trigeminal neuralgia (TN) patients after continuous
      radiofrequency (CRF) combined with pulsed radiofrequency (PRF) treatment of the
      Gasserian ganglion (GG). METHODS: Twenty-one patients were treated with pulsed RF
      for 6 min repeated after rotating the needle tip by 180 degrees , at a pulse
      width of 10 ms and at 45  degrees C. This was followed by conventional RF at 60 
      degrees C for 60 s, repeated after needle rotation by 180 degrees , then finally
      at 65  degrees C for 60 s also repeated after needle rotation by 180 degrees .
      Patients were assessed for pain intensity and consumption of analgesics at
      baseline and 7 days, 1 month, 6 months, and 12 months after the procedure. The
      patients' global impression of change (PGIC) scale was also assessed 7 days, 1
      month, 6 months, and 12 months after the procedure. The incidence of facial
      dysthesia was evaluated 7 days after the procedure. RESULTS: Excellent pain
      relief was achieved for 15 of 21 patients (71.4 %) after 1 week, 1 month, and 6
      months. and for 14 of 21 patients (66.7 %) after 12 months. Consumption of
      analgesics was significantly reduced for more than 6 months, and for fifteen
      patients the PGIC scale result was very much improved 12 months after the
      procedure compared with baseline. Eighteen of the 21 patients (85.7 %)
      experienced facial dysthesia 1 week after the procedure. CONCLUSION: Excellent
      pain relief and reduced consumption of analgesics for more than 6 months were
      observed in patients who received PRF combined with CRF to the GG for treatment
      of idiopathic TN.

PMID- 25987326
TI  - [Penis disorders].

PMID- 25987325
TI  - Efficacy of Cilostazol a selective phosphodiesterase-3 inhibitor in rat model of
      Streptozotocin diabetes induced vascular dementia.
AB  - The present study has been designed to investigate the potential of Cilostazol a
      phosphodiesterase-3 (PDE-3) inhibitor in diabetes-induced vascular dementia (Vad)
      employing Wistar rats. A single dose of Streptozotocin (STZ) was used for the
      induction of diabetes and subsequent Vad in rats. Memory and learning abilities
      of rats were evaluated with Morris water maze (MWM) test. Serum glucose, body
      weight, vascular endothelial function, serum nitrite/nitrate levels, brain
      oxidative stress levels (viz. brain thiobarbituric acid reactive species and
      reduced glutathione levels), inflammatory markers (viz. brain myeloperoxidase
      activity and neutrophil infiltration in the brain hippocampal area) and brain
      acetylcholinesterase activity were also tested. Donepezil was used as positive
      control. Streptozotocin treated animals showed poor performance on MWM indicating
      impairment of learning and memory abilities with a significant reduction in body
      weight, vascular endothelial function, serum nitrite/nitrate levels, along with
      an increase in serum glucose, brain oxidative stress levels, inflammatory changes
      and brain acetylcholinesterase activity. Treatment with selective PDE-3
      inhibitor, Cilostazol significantly attenuated, diabetes-induced impairment of
      learning and memory; endothelial dysfunction, and changes in various biochemical
      parameters. It is concluded that selective PDE-3 inhibitor, Cilostazol may be
      considered as the potential pharmacological agent for the management of diabetes
      induced vascular dementia. 

PMID- 25987327
TI  - [Epispadias and urethral duplication].
AB  - Epispadias is the mildest form of the exstrophy-epispadias complex and rarely
      occurs in an isolated form. The characteristic clinical sign is a mucosal strip
      on the penile dorsum. Clinically, epispadias presents with urinary incontinence.
      Primary surgical correction is recommended at the age of 12 months and should
      only be performed at a specialized center. During follow-up, further bladder neck
      surgery may be necessary. Despite a functional and cosmetically appealing penis,
      psychosocial and psychosexual development of the affected individuals can
      severely be affected. The incidence of urethral duplication remains unclear.
      Several classifications reflect the anatomical variation. The clinical
      presentation depends on the continuity of the duplicated urethra and its
      relationship to the sphincteric mechanism. In addition to clinical examination, a
      voiding cysturethrography is part of the basic diagnostic workup. After
      endoscopic examination an individual operative approach can be defined.

PMID- 25987328
TI  - [Conservative therapy of Peyronie's disease - update 2015].
AB  - Peyronie's disease (PD) is a benign disease of the penis leading to development
      of fibrous plaques at the penile tunica albuginea. PD is a heterogeneous disease
      with variable constellation of symptoms (penile deviation, pain, penile
      shortening, erectile dysfunction). Due to lack of pathophysiological knowledge
      there is no causal therapy of PD. Surgical therapy still represents the gold
      standard for correction of penile deviation. Available conservative treatment
      options vary from oral medical therapy to minimally invasive treatments (e.g.
      iontophoresis) and invasive treatment modalities (e.g. intralesional therapy). A
      gold standard for the conservative therapy of PD does not exist due to the
      nonhomogeneous disease and the variable constellation of symptoms. New
      conservative treatment options like penile traction and also promising treatments
      like intralesional injection therapy with collagenase have to be further
      investigated and prove their efficacy in the long-term. Moreover, well
      structured, standardized, randomized placebo-controlled studies have to be done
      for each of the treatment modalities, so that patients can be offered successful
      and evidence-based conservative therapies in the future. 

PMID- 25987329
TI  - [Operative therapy of Pyronie's disease].
AB  - The operative therapy of Pyronie's disease (penile induration) follows a staged
      scheme. If the deviation is > 45 degrees  a complex operative treatment in the
      sense of plaque incision and excision with subsequent defect coverage is
      necessary. This operation should be carried out under optical magnification to
      safeguard the vessel-nerve bundle. Defect coverage can currently be carried out
      using a collagen fleece with excellent outcome but alternative patches are also
      still available. The focus in patient management is on a realistic preoperative
      estimation of the situation in order to avoid any unrealistic preconceptions and
      expectations by the patient.

PMID- 25987330
TI  - [Diagnosis and management of priapism].
AB  - Priapism is defined as an erection for more than 4 h without sexual stimulation.
      The most common form with nearly 95% is the ischemic or low-flow form, which is
      very painful. The other 5% are comprised of nonischemic high-flow type usually
      caused by a blunt perineal trauma and the recurrent or intermittent so-called
      stuttering priapism. Anamnesis as well as physical and laboratory examination are
      important during the diagnostic workup. Patients who suffer from sickle cell
      anemia are predestined to develop priapism. Priapism constitutes a urological
      emergency because especially the low-flow type has to be treated immediately to
      prevent a long-lasting fibrosis of the corpus cavernosa and a consecutive
      erectile dysfunction. The first step is the puncture and aspiration of blood from
      the corpus cavernosa if necessary combined with the injection of alpha-agonists.
      In case detumescence is not achieved, an operative shunt should be placed after
      an MRI. If there is a complete fibrosis of the corpus cavernosa possibly combined
      with penis deviation the implantation of a penile prosthesis is an option. The
      therapy of high-flow priapism is not as urgent as that of low-flow priapism
      because there is no risk of ischemia. If conservative therapeutic options fail,
      the superselective embolization of the fistula is the treatment of choice. In
      recurrent or intermittent priapism, the goal is to avoid new episodes with drug
      treatment. Because of the low incidence of priapism, it is very difficult to
      recommend and favor one therapeutic procedure.

PMID- 25987331
TI  - [Genetic aspects of erectile dysfunction].
AB  - BACKGROUND: Erectile dysfunction (ED) is a common disorder in man that influences
      the quality of life of the patient and his partner. Known risk factors for ED
      comprise diabetes, coronary artery disease, hypertension but also lifestyle
      modifications such as smoking, diminished physical activity as well as obesity.
      In this manuscript the current scientific literature about genetics and erectile
      dysfunction is reviewed. MATERIALS AND METHODS: A literature search using the
      databank PubMed covering the topics genetics and erectile dysfunction was
      performed and relevant papers selected for presentation. RESULTS: Several aspects
      of genetics and ED are described in the current literature. Association studies
      of candidate polymorphisms and ED risk in comparison to healthy controls is a
      major area of research. Another topic is the genome-wide search for candidate
      polymorphisms with erectile dysfunction. The paper closes with the presentation
      of the pharmacogenomic analysis of treatment response to phosphodiesterase-5
      inhibitors. DISCUSSION: The heterogeneous results of genetic association studies
      are possibly due to small sample sizes of the study population and/or due to
      ethnic differences of the analyzed populations. This underlines the need for
      validation of this data in larger prospective multinational multicenter studies.

PMID- 25987332
TI  - [Conservative therapy of erectile dysfunction].
AB  - The erectile dysfunction (ED) with a prevalence of 19.2% and a steep age-related
      increase up to 53.4% in men over 70 years is a common sexual disorder. Especially
      after market launch of the phosphodiesterase 5 inhibitors the possibility of an
      easy-to-use and well-tolerated therapy is available. In case of nonresponse,
      vasoactive substances can be applied in different forms. In case of an additional
      hypogonadism, testosterone substitution is indicated. Simultaneously the causes
      of ED should always be treated, including a change of lifestyle with elimination
      of exogenous noxa. The use of mechanic tools as single or combination therapy can
      lead to improved erection. This article provides a critical overview of the
      latest conservative therapy options, it explains previous unsuccessful
      therapeutic trials and gives an outlook into potential ED therapy concepts of the
      future.

PMID- 25987333
TI  - [Surgical treatment of erectile dysfunction].
AB  - During the past decades several efforts had been undertaken to treat erectile
      dysfunction by vascular surgery. Today one option survived: Implantation of
      Penile Prostheses. A lot of improvements of the material and the process quality
      lead to very good long term results. Patients with severe erectile dysfunction
      can be recommended in good conscience for implant surgery. 

PMID- 25987334
TI  - [Erratum to: Urogynecology].

PMID- 25987336
TI  - [Immunotherapy for advanced renal cell cancer].

PMID- 25987335
TI  - [Penile dermatoses].
AB  - The diagnostics of penile skin alterations represent a urological and
      dermatological challenge. The spectrum of differential diagnoses ranges from
      benign skin alterations with no clinical significance, through infections,
      vesiculobullous diseases and neoplasms up to acute diseases necessitating
      emergency interventions. Evidence-based therapy concepts are not available for
      all these diseases and due to the rarity an interdisciplinary cooperation is
      expedient and promising. 

PMID- 25987338
TI  - [Chances and risks of Facebook as communication tool in urology].

PMID- 25987339
TI  - [Renal cell carcinoma: Drug therapy and prognostic models].
AB  - Renal cell carcinoma (RCC) represents the sixth-leading cancer-specific cause of
      death worldwide. This is mainly caused by metastatic or locally advanced RCC.
      Approximately 25-30% of patients present with metastasis during the initial
      diagnosis. Furthermore, 20-30% of patients develop metastatic disease following
      initial curative surgery. Metastatic RCC is characterized by a poor prognosis
      with a median overall survival of less than 2 years. Today, targeted therapies
      such as VEGF receptor inhibitors and antagonists as well as mTOR inhibitors
      represent the standard of care in metastatic RCC. Conventional chemotherapies or
      cytokine-based medications have been abandoned due to inferior clinical efficacy
      compared with targeted therapies. In Germany, sunitinib, pazopanib, temsirolimus,
      and bevacizumab have been approved for first-line treatment and sorafenib,
      axitinib, and everolimus for second-line treatment. Prognostic models, assessing
      individual risk profiles, have been developed in the last 15 years, which are
      crucial for the design of trials, patient counseling, and initiation of goal
      directed therapies.

PMID- 25987340
TI  - The thermal impact of phototherapy with concurrent super-pulsed lasers and red
      and infrared LEDs on human skin.
AB  - From the very first reports describing the method of action of phototherapy, the
      effects have been considered to be the result of photochemical and photophysical
      interactions between the absorbed photons and tissue and not related to secondary
      changes in tissue or skin temperature. However, thermal effects have been
      recently reported in dark pigmented skin when irradiated with single wavelengths
      of 810 and 904 nm of low-level laser therapy (LLLT) devices even with doses that
      do not exceed those recommended by the World Association of Laser Therapy (WALT).
      The aim of this study was to evaluate the thermal impact during the concurrent
      use of pulsed red and infrared LEDs and super-pulsed lasers when applied to
      light, medium, and dark pigmented human skin with doses typically seen in
      clinical practice. The study evaluated the skin temperature of 42 healthy
      volunteers (males and females 18 years or older, who presented different
      pigmentations, stratified according to Von Luschan's chromatic scale) via the use
      of a thermographic camera. Active irradiation was performed with using the multi
      diode phototherapy cluster containing four 905-nm super-pulsed laser diodes
      (frequency set to 250 Hz), four 875-nm infrared-emitting diodes, and four 640-nm
      LEDs (manufactured by Multi Radiance MedicalTM, Solon, OH, USA). Each of the four
      doses were tested on each subject: placebo, 0 J (60 s); 10 J (76 s); 30 J (228
      s); and 50 J (380 s). Data were collected during the last 5 s of each dose of
      irradiation and continued for 1 min after the end of each irradiation. No
      significant skin temperature increases were observed among the different skin
      color groups (p > 0.05), age groups (p > 0.05), or gender groups (p > 0.05). Our
      results indicate that the concurrent use of super-pulsed lasers and pulsed red
      and infrared LEDs can be utilized in patients with all types of skin pigmentation
      without concern over safety or excessive tissue heating. Additionally, the doses
      and device utilized in present study have demonstrated positive outcomes in prior
      clinical trials. Therefore, it can be concluded that the effects seen by the
      concurrent use of multiple wavelengths and light sources were the result of
      desirable photobiomodulation effect and not related to thermal influence. 

PMID- 25987341
TI  - Mapping of healthy oral mucosal tissue using diffuse reflectance spectroscopy:
      ratiometric-based total hemoglobin comparative study.
AB  - The objective of this study is to clinically evaluate the diffuse reflectance
      spectroscopy (DRS) ratiometric method for differentiation of normal oral mucosal
      tissues with different histological natures and vascularizations in the oral
      cavity. Twenty-one healthy patients aged 20-44 years were diagnosed as healthy
      and probed with a portable DRS system. Diffuse reflectance spectra were recorded
      in vivo in the range (450-650 nm). In this study, the following three oral
      mucosal tissues were considered: masticatory mucosa, lining mucosa, and
      specialized mucosa. Spectral features based on spectral intensity ratios were
      determined at five specific wavelengths (512, 540, 558, 575, and 620 nm). Total
      hemoglobin based on spectral ratios for the three anatomical regions have also
      been evaluated. The three studied groups representing different anatomical
      regions in the oral cavity were compared using analysis of variance and post hoc
      least significant difference tests. Statistical analysis showed a significant
      difference in the mean of diffuse spectral ratios between the groups (P < 0.05).
      Post hoc test detected significant difference between masticatory mucosa group
      and lining mucosa group (P < 0.05) and between masticatory mucosa group and
      specialized mucosa group (P = 0.000, at ratio 558/620 and P = 0.000, at ratio
      575/620). Significant difference was also found between the lining mucosa group
      and specialized mucosa group (P = 0.000, at ratio 512/558 and P = 0.000, at ratio
      512/575). It has also been shown that spectral ratios at wavelengths 558, 575,
      and 620 nm reveal the greatest difference among the main oral sites in terms of
      total hemoglobin content. Diffuse reflectance spectroscopy might be used for
      creating a DRS databank of normal oral mucosal tissue with specific spectral
      ratios featuring the total hemoglobin concentrations. That would further enhance
      the discrimination of oral tissue for examining the histological nature of oral
      mucosa and diagnosis of early precancerous changes in the oral cavity based on
      non-invasive monitoring of neovascularization. 

PMID- 25987342
TI  - Evolutionary diversity of social amoebae N-glycomes may support interspecific
      autonomy.
AB  - Multiple species of cellular slime mold (CSM) amoebae share overlapping
      subterranean environments near the soil surface. Despite similar life-styles,
      individual species form independent starvation-induced fruiting bodies whose
      spores can renew the life cycle. N-glycans associated with the cell surface
      glycocalyx have been predicted to contribute to interspecific avoidance,
      resistance to pathogens, and prey preference. N-glycans from five CSM species
      that diverged 300-600 million years ago and whose genomes have been sequenced
      were fractionated into neutral and acidic pools and profiled by MALDI-TOF-MS.
      Glycan structure models were refined using linkage specific antibodies,
      exoglycosidase digestions, MALDI-MS/MS, and chromatographic studies. Amoebae of
      the type species Dictyostelium discoideum express modestly trimmed high mannose N
      glycans variably modified with core alpha3-linked Fuc and peripherally decorated
      with 0-2 residues each of beta-GlcNAc, Fuc, methylphosphate and/or sulfate, as
      reported previously. Comparative analyses of D. purpureum, D. fasciculatum,
      Polysphondylium pallidum, and Actyostelium subglobosum revealed that each
      displays a distinctive spectrum of high-mannose species with quantitative
      variations in the extent of these modifications, and qualitative differences
      including retention of Glc, mannose methylation, and absence of a peripheral
      GlcNAc, fucosylation, or sulfation. Starvation-induced development modifies the
      pattern in all species but, except for universally observed increased mannose
      trimming, the N-glycans do not converge to a common profile. Correlations with
      glycogene repertoires will enable future reverse genetic studies to eliminate N
      glycomic differences to test their functions in interspecific relations and
      pathogen evasion. 

PMID- 25987343
TI  - Endourological management of live donors with urolithiasis at the time of donor
      nephrectomy: a single center experience.
AB  - PURPOSE: Live related renal donors with urolithiasis are made suitable for renal
      transplantation in two-stage procedure in most of the centers: first making the
      donor kidney stone free surgically or by ESWL and then proceeding to renal
      transplantation. To reduce the cost and morbidity of two surgical procedures in
      donors, we did a pilot study of removing subcentimeter renal calculi in live
      donors, after explanting the kidney, during bench surgery. MATERIALS AND METHODS:
      We included all prospective renal donors with subcentimeter (4-10 mm) calculi in
      one kidney in our study (n = 14). All these patients underwent standard donor
      evaluation and metabolic work up. After the donor nephrectomy, bench retrograde
      intra-renal surgery (RIRS) with or without pyelotomy was done for stone clearance
      followed by renal transplantation. RESULTS: Stone clearance was achieved in 13
      out of 14 donors. Donors and recipients were followed for 6-24 months. No stone
      recurrence or graft dysfunction was seen in the follow-up period. CONCLUSION: We
      concluded that bench RIRS is an excellent modality in the management of small
      renal calculi in prospective renal donors who are not having metabolically active
      disease. This reduced the cost and morbidity to the donor and minimized waiting
      time for transplant.

PMID- 25987345
TI  - First principles study of magnetoelectric coupling in Co2FeAl/BaTiO3 tunnel
      junctions.
AB  - Critical thickness for ferroelectricity and the magnetoelectric effect of
      Co2FeAl/BaTiO3 multiferroic tunnel junctions (MFTJs) are investigated using first
      principles calculations. The ferroelectric polarization of the barriers can be
      maintained upto a critical thickness of 1.7 nm for both the Co2/TiO2 and
      FeAl/TiO2 interfaces. The magnetoelectric effect is derived from the difference
      in the magnetic moments on interfacial atoms, which is sensitive to the reversal
      of electric polarization. The magnetoelectric coupling is found to be dependent
      on the interfacial electronic hybridizations. Compared with the Co2/TiO2
      interface, more net magnetization change is achieved at the FeAl/TiO2 interface.
      In addition, the in-plane strain effect shows that in-plane compressive strain
      can lead to the enhancement of ferroelectric polarization stability and intensity
      of magnetoelectric coupling. These findings suggest that Co2FeAl/BaTiO3 MFTJs
      could be utilized in the area of electrically controlled magnetism, especially
      the MFTJ with loaded in-plane compressive strain with the FeAl/TiO2 interface. 

PMID- 25987344
TI  - Renalase: Another puzzle piece between hypertension and simple renal cysts?
AB  - BACKGROUND AND AIM: Since renalase is mostly expressed in kidney tubules, simple
      renal cyst (SRC) originates from the kidney tubules, and both conditions are
      related to hypertension, it may be possible that SRC is associated with increased
      renalase levels. Therefore, in the current study we aimed to confirm the relation
      between renalase and epinephrine levels, the association between SRC and renalase
      levels and the association between renalase, blood pressure levels and
      endothelial dysfunction. MATERIALS AND METHODS: We made a cross-sectional study
      including 75 patients with SRC, and 51 controls were included to the study. Flow
      mediated dilatation (FMD) was assessed, and serum renalase and epinephrine levels
      were determined. RESULTS: Patient with SRC had lower renalase, higher epinephrine
      and lower FMD levels when compared to patients without SRC (p < 0.05). Log
      renalase was correlated with log epinephrine (r = -0.302, p = 0.001) and log FMD
      (r = 0.642, p < 0.0001). There was no correlation between renalase and urine
      albumin/creatinine ratio and glomerular filtration rate. In univariate analysis,
      age, glomerular filtration rate, renalase and FMD were associated with the
      presence of SRC. Multivariate regression analysis of factors which are
      statistically significant in univariate analysis showed that age and renalase was
      associated with the presence of SRC. CONCLUSION: We have demonstrated that
      renalase levels were associated with the presence of SRC and endothelial
      dysfunction. Further research is necessary to highlight underlying mechanisms.

PMID- 25987346
TI  - Differentiated thyroid carcinoma in lingual thyroid.
AB  - The lingual thyroid is the most common form of thyroid ectopy. The ectopic tissue
      may display any disease affecting the thyroid, including malignancies, which have
      an estimated incidence of less than 1%. To date only 51 cases of lingual thyroid
      cancer were reported. Analogously to what observed in orthotopic thyroid,
      papillary carcinoma is the predominant histotype in lingual thyroid carcinoma.
      The higher frequency of lingual follicular thyroid carcinoma previously reported
      is possibly related to histological misclassification in some early reports,
      prior to the standardization of histological typing of differentiated thyroid
      carcinomas. Nonetheless, the frequency of the follicular histotype is not
      negligible, accounting for about one-third of the reported cases. Both natural
      history and prognosis of lingual thyroid carcinoma are poorly known, likely
      because of the rarity of the disease and the heterogeneity in the therapeutic
      approach. However, among the cases more recently reported, surgical excision of
      the mass, either alone or followed by radioiodine ablation, is the first-line
      approach, with only two cases treated by radioiodine alone. The nonsignificant
      rate of neoplastic transformation in lingual thyroid should encourage efforts to
      obtain a widely accepted consensus for the management of this rare condition,
      along with standardization of either diagnostic or therapeutic handling of
      malignancies arising in ectopic thyroid.

PMID- 25987348
TI  - Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic
      forms of diabetes mellitus.
AB  - Ghrelin is a hormone that regulates appetite. It is likely to be involved in the
      pathophysiology of varying forms of diabetes. In animal studies, the ghrelin
      expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A).
      Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We
      aimed to assess the circulating ghrelin levels in HNF1A-MODY and in other types
      of diabetes and to evaluate its association with HNF1A mutation status. Our
      cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes
      (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK)
      gene mutation carriers with diabetes as well as 51 healthy controls. Plasma
      ghrelin concentration was measured using the immunoenzymatic assay with
      polyclonal antibody against the C-terminal fragment of its acylated and
      desacylated forms. Ghrelin concentrations were 0.75 +/- 0.32, 0.70 +/- 0.21, 0.50
      +/- 0.20, and 0.40 +/- 0.16 ng/ml in patients with HNF1A-MODY, GCK-MODY, T1DM,
      and T2DM, respectively. The ghrelin levels were higher in HNF1A-MODY and GCK-MODY
      than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in non
      diabetic controls (1.02 +/- 0.29 ng/ml, p < 0.001 for both comparisons). In the
      multivariate linear model, the differences between both MODY groups and common
      diabetes types remained significant. Analysis by a HNF1A mutation type indicated
      that ghrelin concentration is similar in patients with different types of
      sequence differences. Plasma ghrelin level is higher in HNF1A-MODY and GCK-MODY
      than in the common polygenic forms of diabetes.

PMID- 25987347
TI  - Low serum free thyroxine concentrations associate with increased arterial
      stiffness in euthyroid subjects: a population-based cross-sectional study.
AB  - Some studies suggest that even in euthyroid subjects, thyroid function may affect
      arteriosclerotic risk factors. We aimed to determine whether thyroid hormones or
      thyroid autoantibodies are associated with arterial stiffness in middle-aged and
      elderly Chinese subjects with euthyroidism. A cross-sectional, population-based
      study was conducted in Nanjing, China. A total of 812 euthyroid subjects (mean
      age [56.75 +/- 8.34] years; 402 men) without vascular disease and major
      arteriosclerotic risk factors were included. Clinical factors, oral glucose
      tolerance test results, homeostasis model assessment for insulin resistance (HOMA
      IR) results, and serum levels of lipids, free triiodothyronine (FT3), free
      thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid autoantibodies
      were measured. Arterial stiffness was assessed using brachial-ankle pulse wave
      velocity (baPWV). In Pearson correlation analyses, baPWV correlated inversely
      with FT4 (r = -0.146, P < 0.001), but not with FT3 (r = 0.008, P = 0.816) or TSH
      (r = 0.055, P = 0.118). Subsequently, a multiple stepwise regression analysis
      revealed a significant and independent association of FT4 with baPWV in euthyroid
      subjects (beta = -0.076, P = 0.005). After adjusting for potential cardiovascular
      risk factors, mean diastolic blood pressure (DBP), HOMA-IR, and baPWV levels
      decreased across increasing FT4 quartiles (DBP, P < 0.001; HOMA-IR, P < 0.001;
      baPWV, P = 0.003). No difference in baPWV was observed between the positive and
      the negative thyroid antibody groups (15.23 +/- 3.30 m/s vs. 15.73 +/- 3.05 m/s,
      P > 0.05). FT4 levels were inversely associated with arterial stiffness in
      euthyroid subjects. A prospective study is warranted to validate whether subjects
      with low-normal FT4 levels have a high incidence of cardiovascular disease. 

PMID- 25987349
TI  - Optimising the Inflammatory Bowel Disease Unit to Improve Quality of Care: Expert
      Recommendations.
AB  - INTRODUCTION: The best care setting for patients with inflammatory bowel disease
      [IBD] may be in a dedicated unit. Whereas not all gastroenterology units have the
      same resources to develop dedicated IBD facilities and services, there are steps
      that can be taken by any unit to optimise patients' access to interdisciplinary
      expert care. A series of pragmatic recommendations relating to IBD unit
      optimisation have been developed through discussion among a large panel of
      international experts. METHODS: Suggested recommendations were extracted through
      systematic search of published evidence and structured requests for expert
      opinion. Physicians [n = 238] identified as IBD specialists by publications or
      clinical focus on IBD were invited for discussion and recommendation modification
      [Barcelona, Spain; 2014]. Final recommendations were voted on by the group.
      Participants also completed an online survey to evaluate their own experience
      related to IBD units. RESULTS: A total of 60% of attendees completed the survey,
      with 15% self-classifying their centre as a dedicated IBD unit. Only half of
      respondents indicated that they had a defined IBD treatment algorithm in place.
      Key recommendations included the need to develop a multidisciplinary team
      covering specifically-defined specialist expertise in IBD, to instil processes
      that facilitate cross-functional communication and to invest in shared care
      models of IBD management. CONCLUSIONS: Optimising the setup of IBD units will
      require progressive leadership and willingness to challenge the status quo in
      order to provide better quality of care for our patients. IBD units are an
      important step towards harmonising care for IBD across Europe and for
      establishing standards for disease management programmes.

PMID- 25987351
TI  - The Value of Vedolizumab as Rescue Therapy in Moderate-Severe Crohn's Disease
      Patients with Adalimumab Non-response in the USA.
AB  - BACKGROUND AND AIMS: In May 2014, vedolizumab was approved by the Food and Drug
      Administration for the treatment of moderate-to-severe Crohn's disease. In
      clinical practice it is typically used in patients who are primary or secondary
      non-responders to adalimumab [Humira]. We aim to estimate the incremental
      benefits and costs of using vedolizumab as rescue therapy for adalimumab non
      responders. METHODS: A Markov model was used to simulate the clinical course of
      Crohn's disease in a hypothetical cohort of 10,000 patients over a 12-month
      period. The treatment strategies evaluated were adalimumab only [with and without
      dose intensification] and adalimumab and vedolizumab [with and without adalimumab
      dose intensification]. The base case strategy was adalimumab only with 25% of non
      responders undergoing dose intensification. Our primary outcomes were changes in
      costs and quality of life measures over the analytical horizon. RESULTS: In a 1
      year period, initiating vedolizumab as rescue therapy in adalimumab non
      responders reduces the average total cost per patient by 10%, and increases the
      average amount of time spent in remission or mild disease by up to 2 months.
      CONCLUSIONS: Treating on-label adalimumab non-responders with vedolizumab can, in
      the short term, significantly improves the quality of life of Crohn's disease
      patients that do not respond to adalimumab.

PMID- 25987350
TI  - Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans
      Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel
      Disease.
AB  - BACKGROUND AND AIMS: We investigated oral delivery of transforming growth factor
      beta 1 [TGFbeta]- and all-trans retinoic acid [ATRA]-loaded microspheres as
      therapy for gut inflammation in murine models of inflammatory bowel disease
      [IBD]. METHODS: ATRA and TGFbeta were separately encapsulated in poly [lactic-co
      glycolic] acid or polylactic acid microspheres [respectively]. TGFbeta was
      encapsulated using proprietary phase-inversion nanoencapsulation [PIN]
      technology. RESULTS: PIN particles provided sustained release of bioactive
      protein for at least 4 days and were stable for up to 52 weeks when stored at
      either 4(0)C or -20(0)C. In the SCID mouse CD4 + CD25- T cell transfer model of
      IBD, oral treatment starting at disease onset prevented weight loss,
      significantly reduced average disease score [~ 50%], serum amyloid A levels [~ 5
      fold], colon weight-to-length ratio [~ 50%], and histological score [~ 5-fold].
      CONCLUSIONS: Both agents given together outperformed either separately. Highest
      TGFbeta doses and most frequent dose schedule were most effective. Activity was
      associated with a significant increase [45%] in Foxp3 expression by colonic
      lamina propria CD4+ CD25+ T-cells. Activity was also demonstrated in dextran
      sulphate sodium-induced colitis. The data support development of the combination
      product as a novel, targeted immune based therapy for treatment for IBD.

PMID- 25987352
TI  - Relationship Between being Overweight and Iron Deficiency in Adolescents.
AB  - OBJECTIVE: Being overweight has been considered to be a risk factor of iron
      deficiency (ID). The objective of this study was to examine the relationship
      between being overweight and body iron status among Taiwanese adolescents.
      METHODS: A total of 2099 adolescents (1327 female) aged 12-19 years from four
      middle schools and one college in southern Taiwan participated in this study.
      Data on sex, age, body weight, height, hemoglobin concentration, plasma ferritin
      (PF), and serum iron (SI) levels were collected. According to the age- and sex
      specific body mass index (BMI) percentiles, the participants were divided into
      four weight groups: underweight (<5(th) percentile), normal weight (5-84(th)
      percentile), overweight (85-94(th) percentile), and obese (>=95(th) percentile).
      A multivariate logistic regression model was used to estimate the odds ratio (OR)
      and the 95% confidence interval (CI) for each factor. RESULTS: The correlation
      coefficients of linear regression were positive for BMI-hemoglobin and BMI-PF,
      but negative for BMI-SI. Compared with the normal-weight group, the obese group
      had a lower risk of PF level <15 MUg/L with an OR (95% CI) of 0.51 (0.30-0.87)
      but a higher risk of SI <60 MUg/dL with an OR (95% CI) of 1.78 (1.34-2.37). The
      percentages of low PF declined as BMI increased, but the percentages of low SI
      rose, from underweight to obesity groups. CONCLUSION: The relationship between
      being overweight and depleted iron store depends on which indicator is used to
      define the iron deficiency. Being overweight or obese would not be a risk factor
      of ID in adolescents, if ID were defined by PF rather than SI level.

PMID- 25987353
TI  - A theoretical perspective on road safety communication campaigns.
AB  - This paper proposes a theoretical perspective on road safety communication
      campaigns, which may help in identifying the conditions under which such
      campaigns can be effective. The paper proposes that, from a theoretical point of
      view, it is reasonable to assume that road user behaviour is, by and large,
      subjectively rational. This means that road users are assumed to behave the way
      they think is best. If this assumption is accepted, the best theoretical
      prediction is that road safety campaigns consisting of persuasive messages only
      will have no effect on road user behaviour and accordingly no effect on
      accidents. This theoretical prediction is not supported by meta-analyses of
      studies that have evaluated the effects of road safety communication campaigns.
      These analyses conclude that, on the average, such campaigns are associated with
      an accident reduction. The paper discusses whether this finding can be explained
      theoretically. The discussion relies on the distinction made by many modern
      theorists between bounded and perfect rationality. Road user behaviour is
      characterised by bounded rationality. Hence, if road users can gain insight into
      the bounds of their rationality, so that they see advantages to themselves of
      changing behaviour, they are likely to do so. It is, however, largely unknown
      whether such a mechanism explains why some road safety communication campaigns
      have been found to be more effective than others.

PMID- 25987354
TI  - The Evolutionary Tempo of Sex Chromosome Degradation in Carica papaya.
AB  - Genes on non-recombining heterogametic sex chromosomes may degrade over time
      through the irreversible accumulation of deleterious mutations. In papaya, the
      non-recombining male-specific region of the Y (MSY) consists of two evolutionary
      strata corresponding to chromosomal inversions occurring approximately 7.0 and
      1.9 MYA. The step-wise recombination suppression between the papaya X and Y
      allows for a temporal examination of the degeneration progress of the young Y
      chromosome. Comparative evolutionary analyses of 55 X/Y gene pairs showed that Y
      linked genes have more unfavorable substitutions than X-linked genes. However,
      this asymmetric evolutionary pattern is confined to the oldest stratum, and is
      only observed when recently evolved pseudogenes are included in the analysis,
      indicating a slow degeneration tempo of the papaya Y chromosome. Population
      genetic analyses of coding sequence variation of six Y-linked focal loci in the
      oldest evolutionary stratum detected an excess of nonsynonymous polymorphism and
      reduced codon bias relative to autosomal loci. However, this pattern was also
      observed for corresponding X-linked loci. Both the MSY and its corresponding X
      specific region are pericentromeric where recombination has been shown to be
      greatly reduced. Like the MSY region, overall selective efficacy on the X
      specific region may be reduced due to the interference of selective forces
      between highly linked loci, or the Hill-Robertson effect, that is accentuated in
      regions of low or suppressed recombination. Thus, a pattern of gene decay on the
      X-specific region may be explained by relaxed purifying selection and widespread
      genetic hitchhiking due to its pericentromeric location. 

PMID- 25987357
TI  - Lowest effective 131I activity for thyroid remnant ablation of differentiated
      thyroid cancer patients. Dosimetry-based model for estimation.
AB  - AIM: A theoretical dosimetry-based model was applied to estimate the lowest
      effective radioiodine activity for thyroid remnant ablation of low-risk
      differentiated thyroid cancer patients. PATIENTS, METHODS: The model is based on
      the distribution of the absorbed (radiation) dose per administered radioiodine
      activity and the absorbed dose threshold of 300 Gy for thyroid remnants, the
      level believed to destroy most thyroid remnants. For this purpose, 124I PET/CT
      images of 49 thyroidectomised patients were retrospectively analysed to measure
      the distribution of the (average) absorbed doses to thyroid remnant per
      administered 131I activity. The fraction of thyroid remnants that received at
      least 300 Gy was determined for standard activities between 0.37 and 5.55 GBq.
      The lower activity was considered to be equally effective to that obtained with
      higher activity if the (absolute) fraction difference was below 5%. RESULTS: A
      total of 62 thyroid remnants were included. The medians and ranges (in
      parentheses) for the absorbed dose per unit 131I activity were 359 Gy/GBq (34 to
      1825 Gy/GBq). The fractions of thyroid remnants receiving more than 300 Gy at
      different therapy activities (within parentheses) were 60% (1.11 GBq), 76% (1.85
      GBq), 79% (2.22 GBq), and 81-82% for activities between 2.59 and 3.70 GBq. The
      therapy activity of 1.11 GBq is considerably less effective than that of 1.85 or
      2.22 GBq; therapy activities were equally effective in the range between 2.22 to
      3.70 GBq. CONCLUSION: On the basis of the model and the patients' data included,
      the lowest effective therapy activity appears to be approximately 2.2 GBq to
      ablate thyroid remnants. The results of this study may help to guide the design
      of prospective clinical studies.

PMID- 25987355
TI  - Evolution of Enzyme Kinetic Mechanisms.
AB  - This review paper discusses the reciprocal kinetic behaviours of enzymes and the
      evolution of structure-function dichotomy. Kinetic mechanisms have evolved in
      response to alterations in ecological and metabolic conditions. The kinetic
      mechanisms of single-substrate mono-substrate enzyme reactions are easier to
      understand and much simpler than those of bi-bi substrate enzyme reactions. The
      increasing complexities of kinetic mechanisms, as well as the increasing number
      of enzyme subunits, can be used to shed light on the evolution of kinetic
      mechanisms. Enzymes with heterogeneous kinetic mechanisms attempt to achieve
      specific products to subsist. In many organisms, kinetic mechanisms have evolved
      to aid survival in response to changing environmental factors. Enzyme promiscuity
      is defined as adaptation to changing environmental conditions, such as the
      introduction of a toxin or a new carbon source. Enzyme promiscuity is defined as
      adaptation to changing environmental conditions, such as the introduction of a
      toxin or a new carbon source. Enzymes with broad substrate specificity and
      promiscuous properties are believed to be more evolved than single-substrate
      enzymes. This group of enzymes can adapt to changing environmental substrate
      conditions and adjust catalysing mechanisms according to the substrate's
      properties, and their kinetic mechanisms have evolved in response to substrate
      variability. 

PMID- 25987358
TI  - Suspected childhood cancer fast track: increasing referrals, diminishing returns.

PMID- 25987356
TI  - A Proposal for the Evolution of Cathepsin and Silicatein in Sponges.
AB  - Cathepsins are enzymes capable of degrading proteins intracellularly. They occur
      ubiquitously in opisthokonts, but their potential to provide insight across the
      evolutionary transition from protists to metazoans remains poorly investigated.
      Here, we explore the evolution of cathepsins using comparative analyses of
      transcriptomic datasets, focusing on both, protists (closely related to
      metazoans), and early divergent animals (i.e., sponges). We retrieved DNA
      sequences of nine cathepsin types (B, C, D, F, H, L, O, Z, and silicatein) in the
      surveyed taxa. In choanoflagellates, only five types (B, C, L, O, Z) were
      identified, all of them being also found in sponges, indicating that while all
      cathepsins present in protists were conserved across metazoan lineages,
      cathepsins F and H (and probably D) are metazoan acquisitions. The phylogeny of
      cysteine protease cathepsins (excluding cathepsin D) revealed two major lineages:
      lineage B (cathepsins B and C) and lineage L (cathepsins F, H, L, O, Z). In the
      latter lineage, a mutation at the active site of cathepsin L gave rise to
      silicatein, an enzyme exclusively known to date from siliceous sponges and
      involved in the production of their silica spicules. However, we found that
      several sponges with siliceous spicules did not express silicatein genes and
      that, in contrast, several aspiculate sponges did contain silicatein genes. Our
      results suggest that the ability to silicify may have evolved independently
      within sponges, some of them losing this capacity secondarily. We also show that
      most phylogenies based on cathepsin and silicatein genes (except for that of
      cathepsin O) failed to recover the major lineages of sponges. 

PMID- 25987359
TI  - Contribution of recurrent admissions in children and young people to emergency
      hospital admissions: retrospective cohort analysis of hospital episode
      statistics.
AB  - OBJECTIVE: To examine the contribution of recurrent admissions to the high rate
      of emergency admissions among children and young people (CYP) in England, and to
      what extent readmissions are accounted for by patients with chronic conditions.
      DESIGN: All hospital admissions to the National Health Service (NHS) in England
      using hospital episode statistics (HES) from 2009 to 2011 for CYP aged 0-24
      years. We followed CYP for 2 years from discharge of their first emergency
      admission in 2009. We determined the number of subsequent emergency admissions,
      time to next admission, length of stay and the proportion of injury and chronic
      condition admissions measured by diagnostic codes in all following admissions.
      RESULTS: 869 895 children had an index emergency admission in 2009, resulting in
      a further 939 710 admissions (of which 600 322, or 64%, were emergency
      admissions) over the next 2 years. After discharge from the index admission, 32%
      of 274,986 (32%) children were readmitted within 2 years, 26% of these
      readmissions occurring within 30 days of discharge. Recurrent emergency admission
      accounted for 41% of all emergency admissions in the 2-year cohort and 66% of
      inpatient days. 41% of index admissions, but 76% of the recurrent emergency
      admissions, were in children with a chronic condition. CONCLUSIONS: Recurrent
      admissions contribute substantially to total emergency admissions. They often
      occur soon after discharge, and disproportionately affect CYP with chronic
      conditions. Policies aiming to discourage readmissions should consider whether
      they could undermine necessary inpatient care for children with chronic
      conditions.

PMID- 25987360
TI  - Optimization of nanoparticles for cardiovascular tissue engineering.
AB  - Nano-particulate delivery systems have increasingly been playing important roles
      in cardiovascular tissue engineering. Properties of nanoparticles (e.g. size,
      polydispersity, loading capacity, zeta potential, morphology) are essential to
      system functions. Notably, these characteristics are regulated by fabrication
      variables, but in a complicated manner. This raises a great need to optimize
      fabrication process variables to ensure the desired nanoparticle characteristics.
      This paper presents a comprehensive experimental study on this matter, along with
      a novel method, the so-called Geno-Neural approach, to analyze, predict and
      optimize fabrication variables for desired nanoparticle characteristics.
      Specifically, ovalbumin was used as a protein model of growth factors used in
      cardiovascular tissue regeneration, and six fabrication variables were examined
      with regard to their influence on the characteristics of nanoparticles made from
      high molecular weight poly(lactide-co-glycolide). The six-factor five-level
      central composite rotatable design was applied to the conduction of experiments,
      and based on the experimental results, a geno-neural model was developed to
      determine the optimum fabrication conditions. For desired particle sizes of 150,
      200, 250 and 300 nm, respectively, the optimum conditions to achieve the low
      polydispersity index, higher negative zeta potential and higher loading capacity
      were identified based on the developed geno-neural model and then evaluated
      experimentally. The experimental results revealed that the polymer and the
      external aqueous phase concentrations and their interactions with other
      fabrication variables were the most significant variables to affect the size,
      polydispersity index, zeta potential, loading capacity and initial burst release
      of the nanoparticles, while the electron microscopy images of the nanoparticles
      showed their spherical geometries with no sign of large pores or cracks on their
      surfaces. The release study revealed that the onset of the third phase of release
      can be affected by the polymer concentration. Circular dichroism spectroscopy
      indicated that ovalbumin structural integrity is preserved during the
      encapsulation process. Findings from this study would greatly contribute to the
      design of high molecular weight poly(lactide-co-glycolide) nanoparticles for
      prolonged release patterns in cardiovascular engineering. 

PMID- 25987361
TI  - An optimized InCell Western screening technique identifies hexachlorophene as a
      novel potent TDP43 targeting drug.
AB  - TAR DNA binding protein (TDP43) is a DNA- and RNA-binding protein that is
      implicated in several neurodegenerative disorders termed as "TDP43
      proteinopathies" including Alzheimer's disease (AD), amyotrophic lateral
      sclerosis (ALS) and fronto-temporal lobe dementia (FTLD). We have developed an
      InCell Western (ICW) technique for screening TDP targeting drugs in 96 well
      plates. We tested 281 compounds and identified a novel compound hexachlorophene
      (referred to as B10) that showed potent reduction in TDP43 levels. The effect of
      B10 on TDP protein level was validated in two different cellular models:
      endogenous TDP43 expressing N9 microglial cells and TDP43-over-expressing HEK293
      and HeLa cells. We also analyzed effect of B10 on various pathological forms of
      TDP such as the C25 cleaved fragment that localizes to the cytosol, insoluble
      high molecular weight species, and ALS-linked mutants. Our data suggest that B10
      effectively reduces all forms of TDP. Overall, our data suggest that B10 could
      serve as a potential drug molecule for the treatment of AD, ALS and other TDP43
      proteinopathies. 

PMID- 25987362
TI  - Psychogenic Paroxysmal Nonepileptic Events in Children: A Review.
AB  - BACKGROUND: Paroxysmal nonepileptic events are common in children. Events with a
      psychological basis, historically referred to as pseudoseizures, are a large
      subset of paroxysmal nonepileptic events. METHODS: A review of the relevant
      pediatric and adult literature was performed. RESULTS: It was found that these
      events have many semioloigc features similar to epileptic events and can be
      challenging to correctly identify. The use of a detailed history in combination
      with video encephalography and knowledge of psychogenic paroxysmal nonepileptic
      events will facilitate making the correct diagnosis. Paroxysmal nonepileptic
      events are important to identify as comorbid disorders such as depression,
      anxiety disorder, family discord, and school issues are frequent. In addition,
      prior sexual, emotional, and/or physical abuse may be present. CONCLUSIONS:
      Pediatric patients with paroxysmal nonepileptic events need to be recognized in
      order to avoid unnecessary antiepileptic drugs and emergency department or
      hospital visits and to facilitate appropriate psychological intervention to
      address the underlying etiologies. This review will focus on evaluation and
      identification of paroxysmal nonepileptic events, in addition to reviewing the
      various comorbidities, effective treatments, and outcomes for pediatric patients.
      The key differences between pediatric and adult patients with paroxysmal
      nonepileptic events are addressed.

PMID- 25987363
TI  - Multiple Spinal Arachnoid Cysts in a Child.

PMID- 25987364
TI  - Self-assembled organic hexagonal micro-prisms with high second harmonic
      generation efficiency for photonic devices.
AB  - Multiwavelength coherent light sources are key components for circuit integration
      of nanophotonics. Here, we demonstrated highly efficient second harmonic
      generation (SHG) in single-crystalline hexagonal micro-prisms (HMPs) of 3-methyl
      4-methoxy-4'-nitrostilbene (MMONS) prepared via a facile self-assembled method.
      We found that the SHG conversion efficiency (etaSHG) of MMONS HMPs increases with
      increasing the prism side length (d). Local electric field |E|(2) calculations
      suggest that the symmetrical hexagonal prism shape of HMPs supports helically
      propagating modes. The SHG light produced at one end of HMP can be coupled into
      whispering-gallery (WG) like optical modes with a coupling efficiency of 50-80%
      and helically propagates along the length of HMPs toward another end. Based on
      this unique helical propagation of SHG light, we construct an optical
      interconnector by placing a single MMONS HMP on the top of a single micro-ribbon
      of 1,2-diphenyl-2-pyrazoline (DP). These easily fabricated MMONS HMPs can act as
      a coherent source, which adds a key component to the tool box of organic nano-
      and micro-structure optoelectronics. 

PMID- 25987365
TI  - Focalised stimulation using high definition transcranial direct current
      stimulation (HD-tDCS) to investigate declarative verbal learning and memory
      functioning.
AB  - BACKGROUND: Declarative verbal learning and memory are known to be lateralised to
      the dominant hemisphere and to be subserved by a network of structures, including
      those located in frontal and temporal regions. These structures support critical
      components of verbal memory, including working memory, encoding, and retrieval.
      Their relative functional importance in facilitating declarative verbal learning
      and memory, however, remains unclear. OBJECTIVE: To investigate the different
      functional roles of these structures in subserving declarative verbal learning
      and memory performance by applying a more focal form of transcranial direct
      current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to
      examine HD-tDCS effects and electrical field intensity distributions using
      computer modelling. METHODS: HD-tDCS was administered to the left dorsolateral
      prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe
      (LMTL) to stimulate the hippocampus, during learning on a declarative verbal
      memory task. Sixteen healthy participants completed a single blind, intra
      individual cross-over, sham-controlled study which used a Latin Square
      experimental design. Cognitive effects on working memory and sustained attention
      were additionally examined. RESULTS: HD-tDCS to the LDLPFC significantly improved
      the rate of verbal learning (p=0.03, eta(2)=0.29) and speed of responding during
      working memory performance (p=0.02, eta(2)=0.35), but not accuracy (p=0.12,
      eta(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was
      found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed
      that LMTL stimulation resulted in increased recency (p=0.02, eta(2)=0.31) and
      reduced mid-list learning effects (p=0.01, eta(2)=0.39), suggesting an inhibitory
      effect on learning. CONCLUSIONS: HD-tDCS to the LDLPFC facilitates the rate of
      verbal learning and improved efficiency of working memory may underlie
      performance effects. This focal method of administrating tDCS has potential for
      probing and enhancing cognitive functioning.

PMID- 25987367
TI  - Robust and efficient linear registration of white-matter fascicles in the space
      of streamlines.
AB  - The neuroscientific community today is very much interested in analyzing specific
      white matter bundles like the arcuate fasciculus, the corticospinal tract, or the
      recently discovered Aslant tract to study sex differences, lateralization and
      many other connectivity applications. For this reason, experts spend time
      manually segmenting these fascicles and bundles using streamlines obtained from
      diffusion MRI tractography. However, to date, there are very few computational
      tools available to register these fascicles directly so that they can be analyzed
      and their differences quantified across populations. In this paper, we introduce
      a novel, robust and efficient framework to align bundles of streamlines directly
      in the space of streamlines. We call this framework Streamline-based Linear
      Registration. We first show that this method can be used successfully to align
      individual bundles as well as whole brain streamlines. Additionally, if used as a
      piecewise linear registration across many bundles, we show that our novel method
      systematically provides higher overlap (Jaccard indices) than state-of-the-art
      nonlinear image-based registration in the white matter. We also show how our
      novel method can be used to create bundle-specific atlases in a straightforward
      manner and we give an example of a probabilistic atlas construction of the optic
      radiation. In summary, Streamline-based Linear Registration provides a solid
      registration framework for creating new methods to study the white matter and
      perform group-level tractometry analysis. 

PMID- 25987366
TI  - Deep neural network with weight sparsity control and pre-training extracts
      hierarchical features and enhances classification performance: Evidence from
      whole-brain resting-state functional connectivity patterns of schizophrenia.
AB  - Functional connectivity (FC) patterns obtained from resting-state functional
      magnetic resonance imaging data are commonly employed to study neuropsychiatric
      conditions by using pattern classifiers such as the support vector machine (SVM).
      Meanwhile, a deep neural network (DNN) with multiple hidden layers has shown its
      ability to systematically extract lower-to-higher level information of image and
      speech data from lower-to-higher hidden layers, markedly enhancing classification
      accuracy. The objective of this study was to adopt the DNN for whole-brain
      resting-state FC pattern classification of schizophrenia (SZ) patients vs.
      healthy controls (HCs) and identification of aberrant FC patterns associated with
      SZ. We hypothesized that the lower-to-higher level features learned via the DNN
      would significantly enhance the classification accuracy, and proposed an adaptive
      learning algorithm to explicitly control the weight sparsity in each hidden layer
      via L1-norm regularization. Furthermore, the weights were initialized via stacked
      autoencoder based pre-training to further improve the classification performance.
      Classification accuracy was systematically evaluated as a function of (1) the
      number of hidden layers/nodes, (2) the use of L1-norm regularization, (3) the use
      of the pre-training, (4) the use of framewise displacement (FD) removal, and (5)
      the use of anatomical/functional parcellation. Using FC patterns from
      anatomically parcellated regions without FD removal, an error rate of 14.2% was
      achieved by employing three hidden layers and 50 hidden nodes with both L1-norm
      regularization and pre-training, which was substantially lower than the error
      rate from the SVM (22.3%). Moreover, the trained DNN weights (i.e., the learned
      features) were found to represent the hierarchical organization of aberrant FC
      patterns in SZ compared with HC. Specifically, pairs of nodes extracted from the
      lower hidden layer represented sparse FC patterns implicated in SZ, which was
      quantified by using kurtosis/modularity measures and features from the higher
      hidden layer showed holistic/global FC patterns differentiating SZ from HC. Our
      proposed schemes and reported findings attained by using the DNN classifier and
      whole-brain FC data suggest that such approaches show improved ability to learn
      hidden patterns in brain imaging data, which may be useful for developing
      diagnostic tools for SZ and other neuropsychiatric disorders and identifying
      associated aberrant FC patterns.

PMID- 25987368
TI  - Optimization of rs-fMRI Pre-processing for Enhanced Signal-Noise Separation, Test
      Retest Reliability, and Group Discrimination.
AB  - Resting-state functional magnetic resonance imaging (rs-fMRI) has become an
      increasingly important tool in mapping the functional networks of the brain. This
      tool has been used to examine network changes induced by cognitive and emotional
      states, neurological traits, and neuropsychiatric disorders. However, noise that
      remains in the rs-fMRI data after preprocessing has limited the reliability of
      individual-subject results, wherein scanner artifacts, subject movements, and
      other noise sources induce non-neural temporal correlations in the blood oxygen
      level-dependent (BOLD) timeseries. Numerous preprocessing methods have been
      proposed to isolate and remove these confounds; however, the field has not
      coalesced around a standard preprocessing pipeline. In comparisons, these
      preprocessing methods are often assessed with only a single metric of rs-fMRI
      data quality, such as reliability, without considering other aspects in tandem,
      such as signal-to-noise ratio and group discriminability. The present study seeks
      to identify the data preprocessing pipeline that optimizes rs-fMRI data across
      multiple outcome measures. Specifically, we aim to minimize the noise in the data
      and maximize result reliability, while retaining the unique features that
      characterize distinct groups. We examine how these metrics are influenced by
      bandpass filter selection and noise regression in four datasets, totaling 181 rs
      fMRI scans and 38 subject-driven memory scans. Additionally, we perform two
      different rs-fMRI analysis methods - dual regression and region-of-interest based
      functional connectivity - and highlight the preprocessing parameters that
      optimize both approaches. Our results expand upon previous reports of individual
      scan reliability, and demonstrate that preprocessing parameter selection can
      significantly change the noisiness, reliability, and heterogeneity of rs-fMRI
      data. The application of our findings to rs-fMRI data analysis should improve the
      validity and reliability of rs-fMRI results, both at the individual-subject level
      and the group level. 

PMID- 25987369
TI  - Outbreak of multidrug-resistant tuberculosis in two secondary schools.
AB  - OBJECTIVES: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB)
      in two schools METHODS: This was a prospective, observational study of an
      outbreak of MDR-TB in 2 schools located in the towns of Onda and Nules, in the
      Spanish province of Castellon, from the moment of detection in November 2008
      until November 2014, including patient follow-up and contact tracing. RESULTS:
      Five cases of MDR-TB were diagnosed. Overall attack rate was 0.9%, and among the
      contacts traced, 66 had latent tuberculous infection, with an infection rate of
      14.4%. Molecular characterization of the 5M. tuberculosis isolates was performed
      by restriction fragment length polymorphism (RFLP) analysis of the IS6110
      sequence. In all 5 patients, cultures were negative at 4-month follow-up, showing
      the efficacy of the treatment given. No recurrence has been reported to date.
      CONCLUSIONS: In the context of globalization and the increased prevalence of MDR
      TB, outbreaks such as the one presented here are only to be expected. Contact
      tracing, strict follow-up of confirmed cases, the availability of fast diagnostic
      techniques to avoid treatment delay, and chemoprophylaxis, together with the
      molecular characterization of strains, are still essential.

PMID- 25987371
TI  - Different structures of the two peroxisome proliferator-activated receptor gamma
      (PPARgamma) ligand-binding domains in homodimeric complex with partial agonist,
      but not full agonist.
AB  - We designed and synthesized acylsulfonamide derivative (3) as a human peroxisome
      proliferator-activated receptor gamma (hPPARgamma) partial agonist by structural
      modification of hPPARgamma full agonist 1. Co-crystallization of 3 with
      hPPARgamma LBD afforded a homodimeric complex, and X-ray crystallographic
      analysis at 2.1A resolution showed that one of the LBDs adopts a fully active
      structure identical with that in the complex of rosiglitazone, a full agonist;
      however, the other LBD in the complex of 3 exhibits a different (non-fully
      active) structure. Interestingly, the apo-homodimer contained similar LBD
      structures. Intrigued by these results, we surveyed reported X-ray crystal
      structures of partial agonists complexed with hPPARgamma LBD homodimer, and
      identified several types of LBD structures distinct from the fully active
      structure. In contrast, both LBDs in the rosiglitazone complex have the fully
      active structure. These results suggest hPPARgamma partial agonists lack the
      ability to induce fully active LBD. The presence of at least one non-fully active
      LBD in the agonist complex may be a useful criterion to distinguish hPPARgamma
      partial agonists from full agonists. 

PMID- 25987370
TI  - Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine
      derivatives with potent in vitro antitumor activity via Cu-catalyzed three
      component reaction.
AB  - In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel
      structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were
      designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for
      cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and
      KBvin). All of the derivatives showed promising in vitro cytotoxic activity
      against the tested tumor cell lines, and were more potent than irinotecan.
      Significantly, these derivatives exhibited comparable cytotoxicity against KBvin,
      while irinotecan was less active against this cell line. With a concise efficient
      synthesis and potent cytotoxic profiles, especially significant activity towards
      KBvin, these compounds merit further development as a new generation of CPT
      derived PEG-conjugated drug candidates. 

PMID- 25987372
TI  - 9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors.
AB  - The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as
      potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are
      discussed. Optimization for JAK family selectivity led to compounds 14 and 21,
      with greater than 45-fold selectivity for JAK2 over all other members of the JAK
      kinase family. 

PMID- 25987373
TI  - Strongylophorines, meroditerpenoids from the marine sponge Petrosia corticata,
      function as proteasome inhibitors.
AB  - Two new strongylophorine derivatives, along with six known strongylophorines,
      were isolated from the marine sponge Petrosia corticata as proteasome inhibitors.
      Of these, a hemiacetal mixture of strongylophorines-13/-14 was the strongest
      inhibitor of the proteasome with an IC50 of 2.1MUM. 

PMID- 25987374
TI  - Synthesis of 5-isoxazol-3-yl-pyrimidine nucleosides as potential antileishmanial
      agents.
AB  - A simple and practical procedure for the preparation of C5-(isoxazol-3-yl)
      pyrimidine nucleosides through 1,3-dipolar cycloaddition of the in situ formed C5
      nitrile oxide substituted pyrimidine nucleosides with various terminal alkynes is
      presented. Compared with literature procedures, this new method has advantageous
      features such as readily available and inexpensive starting materials, simple
      procedure without using expensive transition metal catalyst, and broad scope of
      substrates. By employing this method, 30 nucleoside analogues were prepared in
      moderate yields. Biological studies on these C5-(isoxazol-3-yl)-pyrimidine
      nucleosides showed that most of them exhibited significant in vitro
      antileishmanial activity. 

PMID- 25987375
TI  - Discovery of a novel Kv7 channel opener as a treatment for epilepsy.
AB  - Facilitating activation, or delaying inactivation, of the native Kv7 channel
      reduces neuronal excitability, which may be beneficial in controlling spontaneous
      electrical activity during epileptic seizures. In an effort to identify a
      compound with such properties, the structure-activity relationship (SAR) and in
      vitro ADME for a series of heterocyclic Kv7.2-7.5 channel openers was explored.
      PF-05020182 (2) demonstrated suitable properties for further testing in vivo
      where it dose-dependently decreased the number of animals exhibiting full tonic
      extension convulsions in response to corneal stimulation in the maximal
      electroshock (MES) assay. In addition, PF-05020182 (2) significantly inhibited
      convulsions in the MES assay at doses tested, consistent with in vitro activity
      measure. The physiochemical properties, in vitro and in vivo activities of PF
      05020182 (2) support further development as an adjunctive treatment of refractory
      epilepsy. 

PMID- 25987376
TI  - DNA specific fluorescent symmetric dimeric bisbenzimidazoles DBP(n): the
      synthesis, spectral properties, and biological activity.
AB  - A series of new fluorescent symmetric dimeric bisbenzimidazoles DBP(n) bearing
      bisbenzimidazole fragments joined by oligomethylene linkers with a central 1,4
      piperazine residue were synthesized. The complex formation of DBP(n) in the DNA
      minor groove was demonstrated. The DBP(n) at micromolar concentrations inhibit in
      vitro eukaryotic DNA topoisomerase I and prokaryotic DNA methyltransferase
      (MTase) M.SssI. The DBP(n) were soluble well in aqueous solutions and could
      penetrate cell and nuclear membranes and stain DNA in live cells. The DBP(n)
      displayed a moderate effect on the reactivation of gene expression. 

PMID- 25987377
TI  - Progress towards small molecule menin-mixed lineage leukemia (MLL) interaction
      inhibitors with in vivo utility.
AB  - A series of substituted hydroxymethyl piperidine small molecule inhibitors of the
      protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) are
      described. Initial members of the series showed good inhibitory disruption of the
      menin-MLL1 interaction but demonstrated poor physicochemical and DMPK properties.
      Utilizing a structure-guided and iterative optimization approach key substituents
      were optimized leading to inhibitors with cell-based activity, improved in vitro
      DMPK parameters, and improved half-lives in rodent PK studies leading to MLPCN
      probe ML399. Ancillary off-target activity remains a parameter for further
      optimization. 

PMID- 25987378
TI  - Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of
      Lawsonia inermis (Henna).
AB  - The methanolic extract of Lawsonia inermis L. (henna) showed significant
      inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the
      constituents isolated from the methanolic extract, luteolin, quercetin, and (+/-)
      eriodictyol showed stronger inhibitory activity than the reference compound,
      arbutin. Several structure-activity relationships of the flavonoids were
      suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the
      double bond between the 2- and 3-positions were important. The active
      constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2
      mRNA expression. The suppression was considered as one of the mechanisms of
      action. Furthermore, the methanolic extract and several constituents, including
      luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to
      play a key role in UV-stimulated melanogenesis in human skin. 

PMID- 25987379
TI  - Understanding and practice of evidence based search strategy among postgraduate
      dental students: a preliminary study.
AB  - BACKGROUND: One of the core attributes of competent practice is the ability to
      locate and analyze high-quality evidence. Research on information seeking
      knowledge of dental graduates is scarce. OBJECTIVE: The objective was to evaluate
      pertinent knowledge and skills on formulation of answerable questions and
      searching skills through the understanding and application of EBP. MATERIAL AND
      METHODS: Participants' understanding and abilities to develop answerable
      questions in application of EBP were assessed through a quasi-experimental study
      design among freshly inducted postgraduate dental students at Dow University of
      Health Sciences. Pre and post workshop activity sessions were conducted and
      assessment was made through a tool that was an adaptation of the Fresno Test. The
      assessments performed were calculated for mean scores and standard deviations to
      draw descriptive results for the participants' understanding of the search items
      and clinical question formulation skills. Wilcoxon-signed rank test was performed
      to compare the pre and post workshop mean scores. RESULTS: Forty two participants
      (females = 20, males = 22) attended the workshop. Pre-workshop knowledge and
      understanding about the terminologies used in EBP was low among participants.
      Post-workshop performance of the participants to formulate a question, find
      evidence and search on PubMed was improved to a "Limited" level. The improvements
      were statistically significant but could not attain "Strong" and "Excellent"
      grades as far as the EBP skills were concerned. CONCLUSION: This study observed a
      potential to improve search skills of dental graduates after their training and
      exposure to search strategies available on databases.

PMID- 25987380
TI  - Sealing/Infiltration of Non-cavitated Proximal Carious Lesions May Lead to Lesion
      Arrest.

PMID- 25987381
TI  - Streptococcus mutans is Vertically Transmitted From Mother to Child.

PMID- 25987382
TI  - Laser Therapy is Safe but not Superior to Conventional Treatment of Peri
      implantitis.

PMID- 25987383
TI  - MTA, Formocresol, and Ferric Sulfate Have Significantly Better Clinical and
      Radiographic Outcomes Than Calcium Hydroxide and Laser Therapies in Primary Molar
      Pulpotomies After 18-24 Months.

PMID- 25987384
TI  - Existing Screening Methods for Oral Cancer are Generally Acceptable to Patients
      in Non-dental Settings.

PMID- 25987385
TI  - Water Fluoridation Has a Pre-eruptive Effect in Preventing Caries in Children.

PMID- 25987386
TI  - A Combination of Acetaminophen/Hydrocodone may not Affect Cold Pulpal Testing in
      Patients With Symptomatic Irreversible Pulpitis.

PMID- 25987387
TI  - An Automated System Targeting Outpatients at High Risk for Oral Cancer Improves
      Recruitment to Screening Programs for Premalignant or Early-stage Cancerous
      Lesions.

PMID- 25987388
TI  - The Hall Technique, a Simplified Method for Placing Stainless Steel Crowns on
      Primary Molars, may be as Successful as Traditionally Placed Crowns.

PMID- 25987389
TI  - The Miller-McEntire Score for Molars Provides an Evidence-based Approach to
      Assigning Periodontal Prognosis for Molar Teeth.

PMID- 25987390
TI  - Coffee consumption has no deleterious effects on periodontal health but its
      benefits are uncertain.

PMID- 25987391
TI  - Hall Technique had Better 1-year Clinical Outcomes for Treating Dental Caries in
      Primary Molars in High-risk Children Compared With Conventional Restoration or
      Non-restorative Approaches.

PMID- 25987392
TI  - Smoking cessation may promote additional benefits to non-surgical periodontal
      therapy in adults with chronic periodontitis.

PMID- 25987393
TI  - A Critical Comment to the Practice of Article "Analysis and Evaluation" Faveri et
      al. J Evid Base Dent Pract 2014;14:70-72.

PMID- 25987394
TI  - Considerations About Designing and Reporting Randomized Clinical Trials--Response
      to the Letter to the Editor From Preus et al.

PMID- 25987395
TI  - Mean platelet volume is a predictor of ST resolution following thrombolysis in
      acute ST elevation myocardial infarction.
AB  - BACKGROUND: Larger mean platelets volumes (MPV) are thrombogenic and frequently
      seen after ST-segment elevation myocardial infarction (STEMI). This study aimed
      to examine the association of MPV and resolution of ST-segment after thrombolysis
      in STEMI patients as and its impact on clinical outcome. METHODS: Patients
      presenting to the emergency department with the diagnosis of first STEMI and were
      referred to thrombolysis were screened. Patients with >=50% ST-segment resolution
      (STR) 90minutes after thrombolysis were assigned as "Responder" and those with
      <50% STR were assigned as "Non-Responders". Demographic, clinical comorbidities
      and risk factor were recorded along with and angiographic data. In-hospital
      occurrence of major adverse cardiac events (MACE), including acute heart failure
      (AHF), reinfarction and death were investigated. Additionally, the patients were
      followed for 6 additional months after their discharge from the hospital.
      RESULTS: STR>=50% was seen in 60.2% of patients after thrombolysis. Responders
      had significantly lower MPV (P=0.001) and the critical MPV values were 8.0
      femtoliter (fL) and 8.2fL in predicting STR and MACE. Patients with MPV >=8.2fL
      had lower probability of STR and higher rates of AHF (P<0.001), and MACE
      (P=0.001) compared to the patients with lower platelet volume. In multivariate
      regression, MPV was an independent predictor of STR (P<0.001) as well as MACE
      (HR=4.8, 95% CI of 1.8-12.4; P=0.001). Triple vessel disease was another
      independent factor that predicted MACE. CONCLUSION: Higher MPV's at admission
      were associated with lower STR and higher occurrence of major adverse cardiac
      events in patients receiving thrombolytic therapy for first time STEMI.

PMID- 25987396
TI  - Dactylosporangium cerinum sp. nov., a novel actinobacterium isolated from the
      rhizosphere of Pinus koraiensis Sieb. et Zucc.
AB  - A novel actinobacterium, designated strain NEAU-TPG4(T) was isolated from
      rhizosphere soil of Pinus koraiensis Sieb. et Zucc. collected from Luobei,
      Heilongjiang Province, north China, and characterized using a polyphasic
      approach. Morphological and chemotaxonomic properties of strain NEAU-TPG4(T) were
      consistent with the description of the genus Dactylosporangium. The strain formed
      finger-shaped sporangia on short sporangiophores that emerged directly from
      substrate hyphae. The cell-wall peptidoglycan consisted of meso- and 3-hydroxy
      diaminopimelic acids; arabinose, xylose and glucose were found as whole-cell
      sugars. The phospholipid profile contained diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. The
      predominant menaquinones were identified as MK-9(H8) and MK-9(H6). The
      predominant cellular fatty acids were identified as iso-C16:0, anteiso-C15:0,
      anteiso-C17:0 and C18:0. Phylogenetic analysis using 16S rRNA gene sequences also
      indicated that the strain should be classified in the genus Dactylosporangium and
      showed that the closest relatives were Dactylosporangium maewongense Japan
      Collection of Microorganism (JCM) 15933(T) (99.6 %), Dactylosporangium siamense
      NBRC 106093(T) (99.6 %), Dactylosporangium aurantiacum JCM 3083(T) (99.5 %) and
      Dactylosporangium luteum JCM 17685(T) (99.5 %). However, the low level of DNA-DNA
      relatedness and several cultural and physiological characteristics allowed the
      strain to be distinguished from its closest relatives. Thus, it is proposed that
      strain NEAU-TPG4(T) represents a novel Dactylosporangium species.
      Dactylosporangium cerinum sp. nov. The type strain of D. cerinum is NEAU-TPG4(T)
      (=CGMCC 4.7152(T) = DSM 46712(T)).

PMID- 25987397
TI  - Modestobacter lapidis sp. nov. and Modestobacter muralis sp. nov., isolated from
      a deteriorated sandstone historic building in Salamanca, Spain.
AB  - A polyphasic study was undertaken to establish the taxonomic status of two
      Modestobacter strains isolated from the surface of deteriorated sandstone of a
      historic building in Salamanca, Spain. The strains, isolates MDVD1(T) and MON
      3.1(T), were found to have chemotaxonomic and morphological properties consistent
      with their classification in the genus Modestobacter and to form distinct
      phyletic lines in the Modestobacter 16S rRNA gene tree. Isolate MDVD1(T) was
      found to be closely related to the type strain of Modestobacter versicolor (98.7
      % similarity) and isolate MON 3.1(T) to the type strain of Modestobacter
      multiseptatus (98.6 % similarity). The isolates were distinguished readily from
      one another and from the Modestobacter type strains by a broad range of
      phenotypic properties, by qualitative and quantitative differences in fatty acid
      profiles and by BOX fingerprint patterns. On the basis of these data, it is
      proposed that the isolates be classified in the genus Modestobacter as
      Modestobacter lapidis sp. nov. and Modestobacter muralis sp. nov., with isolates
      MON 3.1(T) (CECT 8844(T) = DSM 100206(T)) and MDVD1(T) (CECT 8845(T) = DSM
      100205(T)) as the respective type strains.

PMID- 25987398
TI  - The influence of atmospheric pressure on aortic aneurysm rupture--is the diameter
      of the aneurysm important?
AB  - BACKGROUND: The rate of aortic aneurysm rupture correlates with the aneurysm's
      diameter, and a higher rate of rupture is observed in patients with larger
      aneurysms. According to the literature, contradictory results concerning the
      relationship between atmospheric pressure and aneurysm size have been reported.
      AIM: In this paper, we assessed the influence of changes in atmospheric pressure
      on abdominal aneurysm ruptures in relationship to the aneurysm's size. METHODS:
      The records of 223 patients with ruptured abdominal aneurysms were evaluated. All
      of the patients had been admitted to the department in the period 1997-2007 from
      the Silesia region. The atmospheric pressures on the day of the rupture and on
      the days both before the rupture and between the rupture events were compared.
      The size of the aneurysm was also considered in the analysis. RESULTS: There were
      no statistically significant differences in pressure between the days of rupture
      and the remainder of the days within an analysed period. The highest frequency of
      the admission of patients with a ruptured aortic aneurysm was observed during
      periods of winter and spring, when the highest mean values of atmospheric
      pressure were observed; however, this observation was not statistically
      confirmed. A statistically non-significant trend towards the higher rupture of
      large aneurysms (> 7 cm) was observed in the cases where the pressure increased
      between the day before the rupture and the day of the rupture. This trend was
      particularly pronounced in patients suffering from hypertension (p = 0.1).
      CONCLUSIONS: The results of this study do not support the hypothesis that there
      is a direct link between atmospheric pressure values and abdominal aortic
      aneurysm ruptures.

PMID- 25987399
TI  - Long-term temporary pacing with an active fixation lead.
AB  - BACKGROUND: Ensuring a haemodynamically effective cardiac rhythm is a challenge
      in patients waiting for pacemaker reimplantation after transcutaneous lead
      extraction due to an infection of the implanted system. AIM: The authors report a
      retrospective analysis of temporary pacing with an active fixation lead (AFTP)
      connected to an externalised pacemaker in patients after transvenous lead
      extraction (TLE) due to an infection. METHODS: AFTP was used in 34 patients (12
      women) aged from 38 to 88 years (mean 67.5 years). This represented 24.5% of the
      population of patients undergoing TLE due to infective indications. In 32 cases,
      the indication for temporary pacing was atrioventricular block, and in 2 patients
      sick sinus syndrome. The lead was implanted via the internal jugular vein
      puncture into the right ventricle in 33 cases and into the right atrium in 1
      case. Leads were secured to the skin and attached to externalized pacemakers.
      RESULTS: AFTP was used for 4 to 26 days (average 14.5 days). Re-implantation was
      performed in 29 patients (85.3% of the study group). There was no early infection
      recurrence. Three patients died during AFTP (8.8% of the study group), including
      two due to septic shock, and a cardiac arrest due to pulseless electrical
      activity in another patient. CONCLUSIONS: Temporary pacing with an active
      fixation lead is an effective and safe method to ensure a hemodynamically stable
      heart rhythm for a period ranging from a few to several days after the surgery in
      patients after transcutaneous lead extraction due to infective indications.

PMID- 25987400
TI  - Trends in pharmacological therapy of patients referred for coronary artery bypass
      grafting between 2004 and 2008: a single-centre study.
AB  - BACKGROUND: Previous reports of pharmacological treatment concerning the surgical
      approach to coronary artery disease emphasise the underused possibilities of
      pharmacological treatment. AIM: To evaluate trends in the level of compliance
      between the pharmacological treatment administered in clinical practice and
      formal guidelines in patients undergoing coronary artery bypass grafting (CABG).
      METHODS: For this retrospective study, medical data from 2827 consecutive
      patients treated in a single cardiac surgery centre from 2004 to 2008 were
      collected. Among them, 1253 underwent surgical procedures as isolated CABG and
      were enrolled in the study. The pharmacological treatment was analysed at two
      points of the perioperative period: the day of admission to hospital and the day
      of discharge from hospital. We collected information about the following groups
      of drugs prescribed: aspirin, b-blockers, angiotensin converting enzyme
      inhibitors (ACEI), statins, and sartans. RESULTS: Before surgery, 89.78% of the
      total population of patients received b-blockers, 81.56% ACEI, 88.27% statins,
      and 3.19% sartans. After CABG, 94.48% of patients received aspirin, 96.04% b
      blockers, 85.16% ACEI, 92.09% statins, and 2.14% sartans. During the years
      analysed, a declining trend away from preoperative prescription of b-blockers (p
      < 0.001), ACEI (p < 0.001), and statins (p < 0.001) was observed. In contrast,
      sartans (p < 0.01) were more often administered over time. At the date of
      discharge, the tendency to prescribe b-blockers (p < 0.05), ACEI (p < 0.001), and
      statins (p < 0.001) was also declining. CONCLUSIONS: Pharmacological treatment of
      ischaemic heart disease in the pre- and postoperative period was underutilised.
      Positive changes were observed in comparison to previous reports from other
      countries.

PMID- 25987402
TI  - A novel life-threatening mutation in long QT2 syndrome.
AB  - BACKGROUND AND AIM: The aim of the report was to present a novel mutation in
      KCNH2 in a family with life-threatening long QT syndrome. METHODS: A genetic
      study using the method of next generation sequencing was performed in a 47-year
      old woman after several episodes of syncope and torsade de pointes after sudden
      stress, with familial history of sudden death in first-degree female relatives.
      The study was performed also in her three asymptomatic children. Prolongation of
      QTc and typical ECG pattern of long QT2 were seen in the index case and in her
      youngest son. RESULTS: Novel mutations (p.F617V) in exon 7 of KCNH2 were found in
      the index case and in her youngest son. CONCLUSIONS: A novel heterozygous
      missense mutation in exon 7 of KCNH2 gene, causing a protein change p.F617V, was
      found in a family with life-threatening arrhythmias in women and clinical outcome
      typical for long QT2 syndrome.

PMID- 25987401
TI  - Effects of outpatient followed by home-based telemonitored cardiac rehabilitation
      in patients with coronary artery disease.
AB  - BACKGROUND: Cardiac rehabilitation (CR) has been shown to reduce the
      cardiovascular mortality of patients with coronary artery disease (CAD) and help
      people to return to professional work. Unfortunately, limited accessibility and
      low participation levels present persistent challenges in almost all countries
      where CR is available. Applying telerehabilitation provides an opportunity to
      improve the implementation of and adherence to CR, and it seems that the hybrid
      form of training may be the optimal approach due to its cost-effectiveness and
      feasibility for patients referred by a social insurance institution. AIM: To
      present the clinical characteristics and evaluate the effects of hybrid:
      outpatient followed by home-based cardiac telerehabilitation in patients with CAD
      in terms of exercise tolerance, safety, and adherence to the programme. METHODS:
      A total of 125 patients (112 men, 13 women) with CAD, aged 58.3 +/- 4.5 years,
      underwent a five-week training programme (TP) consisting of 19-22 exercise
      training sessions. The first stage of TP was performed in the ambulatory form of
      CR in hospital; then, patients continued to be telemonitored TP at home (hybrid
      model of cardiac rehabilitation - HCR). Before and after completing CR, all
      patients underwent a symptom-limited treadmill exercise stress test. Adherence
      was reported by the number of dropouts from the TP. RESULTS: The number of days
      of absence in the HCR programme was 1.50 +/- 4.07 days. There were significant
      improvements (p < 0.05) in some measured variables after HCR in the exercise
      test: max. workload: 7.86 +/- 2.59 METs vs. 8.88 +/- 2.67 METs; heart rate (HR)
      at rest: 77.59 +/- 12.53 bpm vs. 73.01 +/- 11.57 bpm; systolic blood pressure at
      rest: 136.69 +/- 17.19 mm Hg vs. 130.92 +/- 18.95 mm Hg; double product at rest:
      10623.33 +/- 2262.97 vs. 9567.50 +/- 2116.81; HRR1: 97.46 +/- 18.27 bpm vs. 91.07
      +/- 19.19 bpm; and, NYHA class: 1.18 +/- 0.48 vs. 1.12 +/- 0.35. CONCLUSIONS: In
      patients with documented CAD, HCR is feasible and safe, and adherence is good.
      Most patients were on social rehabilitation benefit, had a smoking history, and
      suffered from hypertension, obesity, or were overweight. A hybrid model of CR
      improved exercise tolerance.

PMID- 25987403
TI  - Impaired aortic function in patients with coeliac disease.
AB  - BACKGROUND AND AIM: We aimed to investigate the association between aortic
      function (aortic stiffness index, aortic strain, and aortic distensibility),
      which is a predictor of atherosclerosis, and coeliac disease (CD). METHODS:
      Thirty-six patients with CD and 35 control subjects were included in the study.
      Serological screening was performed to determine the levels of auto-immune
      markers, including anti-gliadin immunoglobulin (Ig)A and IgG, and anti-tissue
      transglutaminase antibodies. Aortic distensibility, aortic strain, and aortic
      stiffness index were calculated using echocardiography. RESULTS: Aortic strain
      and aortic distensibility were significantly lower in patients with CD than in
      control subjects (0.07 [0.03-0.14] vs. 0.09 [0.06-0.15], p < 0.001; 0.0036 +/-
      0.0012 vs. 0.0051 +/- 0.0014, p < 0.001, respectively). However, the aortic
      stiffness index was significantly higher in patients with CD than in controls
      (1.14 [0.57-2.69] vs. 0.91 [0.59-1.92], p = 0.002). Coeliac disease was the only
      independent parameter that was correlated with aortic strain, aortic stiffness
      index, and aortic distensibility (b = -0.427, p < 0.001; b = 0.375, p = 0.003; b
      = -0.434, p < 0.001, respectively). CONCLUSIONS: In this study, we showed
      deteriorated aortic functions by echocardiography in CD patients, which predicted
      subclinical atherosclerosis. Because deteriorated aortic functions is a strong
      predictor of future cardiovascular events, close cooperation with cardiologists
      and gastroenterologists is needed in the management of CD patients, and increased
      awareness of ischaemic heart disease risk factors in these patients and
      healthcare providers is warranted.

PMID- 25987404
TI  - Relation of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio with
      coronary artery disease severity in patients undergoing coronary angiography.
AB  - BACKGROUND: Atherosclerosis is a chronic systemic inflammatory disease.
      Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are
      systemic inflammatory markers that are correlated with poor cardiovascular
      outcomes. AIM: To explore the relation of NLR and PLR with severity of coronary
      artery disease (CAD). METHODS: The study population consisted of 180 consecutive
      patients who underwent elective coronary angiography (CAG). While 100 patients
      (22 female, mean age: 60.6 +/- 12.6 years) had abnormal CAG, 80 patients (44
      female, mean age: 57.2 +/- 10.9 years) had normal CAG. NLR and PLR were
      calculated as the ratio of neutrophil count to lymphocyte count and as the ratio
      of platelet count to lymphocyte count, respectively. RESULTS: Although age
      distribution was similar between the two groups (p = 0.073), female gender was
      significantly higher in the normal CAG group (p < 0.001). Patients with abnormal
      CAG had significantly higher NLR and PLR when compared to patients with normal
      CAG (3.7 +/- 2.6 vs. 2.2 +/- 1.7, p < 0.001 and 125.9 +/- 72.3 vs. 102.6 +/-
      33.8, p = 0.027, respectively). NLR and PLR were significantly correlated with
      SYNTAX score and GENSINI score. In logistic regression analyses, only NLR (odds
      ratio: 1.576, confidence interval: 1.198-2.072, p = 0.001) was an independent
      predictor of CAD. An NLR of 2.3 or higher predicted the CAD with a sensitivity of
      66% and specificity of 70%. CONCLUSIONS: NLR and PLR seem to be a simple method
      to predict severity of CAD in patients undergoing elective CAG, and it may be
      part of cardiovascular examination before CAG.

PMID- 25987405
TI  - Complaints of neurotic patients that are of interest for a cardiologist.
AB  - BACKGROUND: Patients in various areas of medicine report symptoms that are
      unexplained by other medical reasons than psychological/psychiatric. Some of them
      urgently seek treatment due to cardiovascular complaints, mostly rapid heart
      rate, palpitations and chest pain. Typical cardiac investigations, usually
      showing no organic reasons for these conditions, bring little information about
      stressful life events and psychological predispositions of these patients.
      Identification of coexistence of "cardiac" symptoms with other symptoms typical
      for neurotic disorders and difficult life circumstances may facilitate not only
      psychiatric diagnosis but also evaluation by cardiologists, primary care
      physicians, and other specialists. AIM: To determine the psychosocial context of
      psychogenic "pseudocardiac" symptoms and their coexistence with other symptoms in
      patients with neurotic disorders. METHODS: Medical records of patients from the
      years 1980-2002 that included self-administered questionnaires transformed into
      an anonymised database were examined. An analysis of the relationship between
      symptoms reported in the Symptom Checklist and biographical circumstances
      described in the Life Inventory before admission to a psychotherapy day clinic
      for patients with neurotic disorders was performed using simple logistic
      regression with estimation of odds ratios and their 95% confidence intervals.
      RESULTS: The symptoms of tachycardia/palpitations and chest pain were very
      common, present in most subjects, and were significantly associated with such
      circumstances as suboptimal conflict solving by passive aggression or quarrels,
      uncertainty in the relationship, a sense of being inferior to the partner, and
      poor financial situation. In addition, these "pseudocardiac" symptoms were also
      associated with such childhood reminiscences as origin from a large low income
      family, feeling that the family of origin was inferior to others, and experience
      of parental hostility or lack of support. CONCLUSIONS: Physicians of all
      specialties who deal with patients experiencing pseudocardiac symptoms should
      expect their psychological background and perform a simple interview to identify
      the presence of adverse biographical circumstances described above.
      Identification and discussing these difficult experiences with the patients may
      help to convince them to seek psychological support or psychotherapy.

PMID- 25987406
TI  - Diagnostic performance of myocardial perfusion single-photon emission computed
      tomography with attenuation correction.
AB  - BACKGROUND: Myocardial perfusion single-photon emission computed tomography
      (SPECT) is one of the basic tools used for the purpose of diagnosis of coronary
      artery disease (CAD), prognosis of its unfavourable consequences, and evaluation
      of therapy effectiveness. However, its efficacy is compromised by a relatively
      low specificity of detection of perfusion defects, which is attributed to
      attenuation of gamma rays inside the patient's body, causing artefacts
      erroneously taken for perfusion defects. It is expected that attenuation
      correction (AC) could eliminate such artefacts. AIM: To evaluate whether visual,
      semi-quantitative analysis of attenuation-corrected myocardial perfusion imaging
      provides an advantage over a non-corrected study. METHODS: A retrospective study
      applying AC was performed in 107 patients who had coronary angiography within
      three months. Patients underwent a stress/rest Tc-99m methoxyisobutylisonitrile
      (MIBI, POLATOM) double day SPECT/CT myocardial perfusion imaging. Images were
      analysed by two experienced nuclear medicine specialists (a consensus) applying a
      visual semiquantitative method. Coronary angiography findings were used as a
      reference for the analysis of diagnostic performance of myocardial perfusion
      study protocols. RESULTS: AC increased the specificity of detection of CAD in the
      whole group of patients from 63% to 86% (p = 0.0005), with a slight reduction in
      sensitivity (from 83% to 79%). The improved specificity was also noted in
      subgroups of male and female patients. Accuracy in the whole group of patients
      increased from 71% to 83% (p = 0.01). AC improved the specificity and accuracy of
      the method in the detection of perfusion defects in the right coronary artery
      (RCA) area from 73% to 88% (p = 0.005) and from 74% to 83% (p = 0.04),
      respectively, and the accuracy of the method in the left anterior descending
      (LAD) artery area from 79% to 87% (p = 0.043). It also reduced the number of
      ambiguous results of the study. CONCLUSIONS: AC improved the diagnostic
      performance of myocardial perfusion study in the detection of CAD and
      identification of critically stenosed LAD and RCA vessels, with enhanced comfort
      of study interpretation.

PMID- 25987407
TI  - Increased intraventricular pressures are as harmful as the electrophysiological
      substrate of heart failure in favoring sustained reentry in the swine heart.
AB  - BACKGROUND: Heart failure (HF) electrophysiological remodeling (HF-ER) often
      includes the effect of chronically increased intraventricular pressures (IVPs)
      and promotes ventricular tachycardia/ventricular fibrillation (VT/VF). In
      addition, acutely increased IVPs have been associated with a higher rate of VT/VF
      episodes in chronic HF. OBJECTIVE: We hypothesized that increased IVPs and/or an
      ionic-imbalanced (acidified), catecholamine-rich (adrenergic) milieu (AA milieu)
      may contribute as much as HF-ER to the substrate for reentry in HF. We used a
      porcine model of tachycardiomyopathy and evaluated the individual/combined
      contributions of (1) increased IVPs, (2) HF-ER, and (3) an AA milieu. METHODS: HF
      ER was induced in 7 pigs by rapid pacing. Seven pigs were used as controls.
      Hearts were isolated and Langendorff perfused. Programmed ventricular stimulation
      was conducted under low or increased IVP and normal/AA milieu (4 combinations).
      Epicardial optical mapping was used to quantify conduction velocity (CV), action
      potential duration (APD), and dispersion of repolarization (DoR). RESULTS: HF-ER
      decreased CV (-34%; P = .002) and increased APD (11%; P = .024) and DoR (21%; P =
      .007). Increased IVP amplified DoR (36%; P < .001) and decreased CV (-17%; P =
      .001) and APD (-8%; P < .001). The AA milieu consistently modified only APD (-9%;
      P < .001) and led to amplified inter-/intra-subject heterogeneity. Increased IVP
      similarly raised the odds of inducing sustained VT/VF as the presence of HF-ER
      (>6-fold). CONCLUSION: By magnifying DoR, decreasing CV, and shortening APD,
      increased IVP was as harmful as HF-ER in favoring the substrate for sustained
      reentry in this model. The AA milieu contributed to a much lesser extent. Thus, a
      stricter control of IVP might be postulated as a useful add-on antiarrhythmic
      strategy in HF.

PMID- 25987408
TI  - Construction of intracardiac vectorcardiogram from implantable cardioverter
      defibrillator intracardiac electrograms.
AB  - We constructed an intracardiac vectorcardiogram from 3 configurations of
      intracardiac cardiovertor defibrilator (ICD) electrograms (EGMs). Six distinctive
      3 lead combinations were selected out of five leads: can to right ventricular
      coil (RVC); RVC to superior vena cava coil (SVC); atrial lead tip (A-tip) to
      right ventricular (RV)-ring; can to RV-ring; RV-tip to RVC, in a patient with
      dual chamber ICD. Surface spatial QRS-T angle (119.8 degrees ) was similar to
      intracardiac spatial QRS-T angle derived from ICD EGMs combination A (101.3
      degrees ), B (96.1 degrees ), C (92.8 degrees ), D (95.2), E (99.0), F (96.2) and
      median (101.5). Future validation of the novel method is needed.

PMID- 25987409
TI  - Intra-individual ECG changes over 25 years: How long can elective ECGs be used as
      reference for acute ischemia detection?
AB  - BACKGROUND: The guidelines advocate, in patients with chest pain, comparison of
      the acute ECG with a previously made, non-ischemic ECG that serves as a
      reference, to corroborate the working diagnosis of acute coronary syndrome (ACS).
      Our approach of this serial comparison is to compute the differences between the
      ST vectors at the J point and 60 ms thereafter (?ST(J+0), ?ST(J+60)) and between
      the ventricular gradient (VG) vectors (?VG). In the current study, we investigate
      if reference ECGs remain valid in time. METHODS: We studied 6 elective non
      ischemic ECGs (ECG0, ECG1, ..., ECG5), 5 years apart, in 88 patients. Within each
      patient, serial comparisons were done 1) between all successive ECGs, and 2)
      between each of ECG1, ECG2, ..., ECG5 and ECG0, computing, in addition to
      ?ST(J+0), ?ST(J+60) and ?VG, the difference in heart rates, ?HR. Additionally,
      relevant clinical events and the diagnoses associated with each ECG were
      collected. Linear regression was used to assess trends in ?ST(J+0), ?ST(J+60) and
      ?VG; multiple linear regression was used to assess the influence of the clinical
      events and diagnoses on ?ST(J+0), ?ST(J+60) and ?VG. RESULTS: There were no
      trends in the differences between successive ECGs. Positive trends were seen with
      increasing time lapses between ECGs: ?ST(J+0), ?ST(J+60) and ?VG increased per
      year by 0.65 MUV, 1.45 MUV and 3.69 mV?ms, respectively. Extrapolation to a time
      lapse of 0 yielded 50.92 MUV, 36.63 MUV and 20.91 mV?ms for the short-term
      reproducibility of ?ST(J+0), ?ST(J+60) and ?VG, respectively. Multiple linear
      regression revealed that clinical variables could explain only 10%, 17% and 13%
      of the variability in ?ST(J+0), ?ST(J+60) and ?VG, respectively. CONCLUSION: With
      a view on ischemia detection thresholds in the order of magnitude of 58 MUV for
      ?ST and 26 mV.ms for ?VG, our study suggests that it is important to have a
      recent ECG available for the detection of myocardial ischemia, as an "aged" ECG
      may have lost its validity as a reference.

PMID- 25987410
TI  - Cardiac memory in cardiac resynchronization therapy: A vectorcardiographic
      comparison of biventricular and left ventricular pacing.
AB  - INTRODUCTION: "Cardiac memory" (CM) refers to a change in repolarization induced
      by an altered pathway of activation, manifested after resumption of spontaneous
      ventricular activation (SVA). AIMS: To investigate for the first time in humans
      the effects of left ventricular (LV) pacing on CM development through
      vectorcardiography (VCG). METHODS: We studied 28 patients with heart failure (HF)
      and left bundle branch block (LBBB) treated with cardiac resynchronization
      therapy (CRT). Fourteen patients underwent biventricular (BIV) stimulation; the
      other 14 underwent LV stimulation only. VCG was acquired during SVA at baseline
      and during AAI and DDD pacing immediately after and 7 and 90 days after the
      implant. RESULTS: At baseline, in both groups, the QRS and T vectors angles were
      those specific of LBBB pattern. During DDD pacing, QRS vector angle changed to
      the right and upward in BIV patients while no significant differences were
      observed in LV patients. During AAI pacing, T vector angle changed significantly
      in BIV patients, following the direction of the paced QRS and amplitude
      significantly increased. In LV patients no significant differences in T vector
      angles were observed. Only T vector amplitude significantly increased at 7 days
      (p=0.03) and at 90 days (p=0.008 vs baseline). CONCLUSION: In patients with LBBB,
      BIV pacing induces cardiac memory development as a significant change in T vector
      magnitude and angle, while LV pacing doesn't induce significant modifications in
      QRS and T vector angles and CM is manifested only as a significant T vector
      amplitude change.

PMID- 25987411
TI  - Aggressive and Prosocial? Examining Latent Profiles of Behavior, Social Status,
      Machiavellianism, and Empathy.
AB  - The present study tests whether aggression and prosocial behavior can coexist as
      part of a socially functional and adaptive profile among early adolescents. Using
      a person-centered approach, the study examined early adolescents' likelihood of
      being classified into profiles involving aggressive and prosocial behavior,
      social status (popular, liked, cool), machiavellianism, and both affective and
      cognitive components of empathy (empathic concern and perspective taking,
      respectively). Participants were 1170 early adolescents (10-12 years of age; 52%
      male) from four schools in metropolitan Santiago, Chile. Through latent profile
      analysis, three profiles emerged (normative-low aggressive, high prosocial-low
      aggressive, and high aggressive-high popular status). Both empathic concern and
      perspective taking were higher in the high prosocial-low aggressive profile,
      whereas the high aggressive-high popular status profile had the lowest scores on
      both empathy components as well as machiavellianism. No profile emerged where
      aggressive and prosocial behaviors were found to co-exist, or to be significantly
      above the mean. The results underscore that aggressive behavior is highly
      contextual and likely culturally specific, and that the study of behavioral
      profiles should consider social status as well as socio-emotional adjustment
      indicators. These complex associations should be taken into consideration when
      planning prevention and intervention efforts to reduce aggression or school
      bullying and to promote positive peer relationships.

PMID- 25987412
TI  - Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry Enables
      Multiplex, Quantitative Pharmacodynamic Studies of Phospho-Signaling.
AB  - In most cell signaling experiments, analytes are measured one Western blot lane
      at a time in a semiquantitative and often poorly specific manner, limiting our
      understanding of network biology and hindering the translation of novel
      therapeutics and diagnostics. We show the feasibility of using multiplex immuno
      MRM for phospho-pharmacodynamic measurements, establishing the potential for
      rapid and precise quantification of cell signaling networks. A 69-plex immuno-MRM
      assay targeting the DNA damage response network was developed and characterized
      by response curves and determinations of intra- and inter-assay repeatability.
      The linear range was >= 3 orders of magnitude, the median limit of quantification
      was 2.0 fmol/mg, the median intra-assay variability was 10% CV, and the median
      interassay variability was 16% CV. The assay was applied in proof-of-concept
      studies to immortalized and primary human cells and surgically excised cancer
      tissues to quantify exposure-response relationships and the effects of a genomic
      variant (ATM kinase mutation) or pharmacologic (kinase) inhibitor. The study
      shows the utility of multiplex immuno-MRM for simultaneous quantification of
      phosphorylated and nonmodified peptides, showing feasibility for development of
      targeted assay panels to cell signaling networks.

PMID- 25987413
TI  - A Scalable Approach for Protein False Discovery Rate Estimation in Large
      Proteomic Data Sets.
AB  - Calculating the number of confidently identified proteins and estimating false
      discovery rate (FDR) is a challenge when analyzing very large proteomic data sets
      such as entire human proteomes. Biological and technical heterogeneity in
      proteomic experiments further add to the challenge and there are strong
      differences in opinion regarding the conceptual validity of a protein FDR and no
      consensus regarding the methodology for protein FDR determination. There are also
      limitations inherent to the widely used classic target-decoy strategy that
      particularly show when analyzing very large data sets and that lead to a strong
      over-representation of decoy identifications. In this study, we investigated the
      merits of the classic, as well as a novel target-decoy-based protein FDR
      estimation approach, taking advantage of a heterogeneous data collection
      comprised of ~19,000 LC-MS/MS runs deposited in ProteomicsDB
      (https://www.proteomicsdb.org). The "picked" protein FDR approach treats target
      and decoy sequences of the same protein as a pair rather than as individual
      entities and chooses either the target or the decoy sequence depending on which
      receives the highest score. We investigated the performance of this approach in
      combination with q-value based peptide scoring to normalize sample-, instrument-,
      and search engine-specific differences. The "picked" target-decoy strategy
      performed best when protein scoring was based on the best peptide q-value for
      each protein yielding a stable number of true positive protein identifications
      over a wide range of q-value thresholds. We show that this simple and unbiased
      strategy eliminates a conceptual issue in the commonly used "classic" protein FDR
      approach that causes overprediction of false-positive protein identification in
      large data sets. The approach scales from small to very large data sets without
      losing performance, consistently increases the number of true-positive protein
      identifications and is readily implemented in proteomics analysis software.

PMID- 25987415
TI  - Hyperammonemic encephalopathy after adjunction of phenobarbital to chronic
      topiramate and oxcarbazepine therapy.

PMID- 25987416
TI  - New cardiovascular targets to prevent late onset Alzheimer disease.
AB  - The prevalence of dementia rises to between 20% and 40% with advancing age. The
      dominant cause of dementia in approximately 70% of these patients is Alzheimer
      disease. There is no effective disease-modifying pharmaceutical treatment for
      this neurodegenerative disease. A wide range of Alzheimer drugs that appeared
      effective in animal models have recently failed to show clinical benefit in
      patients. However, hopeful news has emerged from recent studies that suggest that
      therapeutic strategies aimed at reducing cardiovascular disease may also reduce
      the prevalence of dementia due to Alzheimer disease. This review summarizes the
      evidence for this link between cardiovascular disease and late onset Alzheimer
      dementia. Only evidence from human research is considered here. Longitudinal
      studies show an association between high blood pressure and pathological
      accumulation of the protein amyloid-beta42, and an even stronger association
      between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid
      beta42 accumulation is considered to be an early marker of Alzheimer disease, and
      increases the risk of subsequent cognitive decline and development of dementia.
      These observations could provide an explanation for recent observations of
      reduced dementia prevalence associated with improved cardiovascular care. 

PMID- 25987414
TI  - MS1 Peptide Ion Intensity Chromatograms in MS2 (SWATH) Data Independent
      Acquisitions. Improving Post Acquisition Analysis of Proteomic Experiments.
AB  - Quantitative analysis of discovery-based proteomic workflows now relies on high
      throughput large-scale methods for identification and quantitation of proteins
      and post-translational modifications. Advancements in label-free quantitative
      techniques, using either data-dependent or data-independent mass spectrometric
      acquisitions, have coincided with improved instrumentation featuring greater
      precision, increased mass accuracy, and faster scan speeds. We recently reported
      on a new quantitative method called MS1 Filtering (Schilling et al. (2012) Mol.
      Cell. Proteomics 11, 202-214) for processing data-independent MS1 ion intensity
      chromatograms from peptide analytes using the Skyline software platform. In
      contrast, data-independent acquisitions from MS2 scans, or SWATH, can quantify
      all fragment ion intensities when reference spectra are available. As each SWATH
      acquisition cycle typically contains an MS1 scan, these two independent label
      free quantitative approaches can be acquired in a single experiment. Here, we
      have expanded the capability of Skyline to extract both MS1 and MS2 ion intensity
      chromatograms from a single SWATH data-independent acquisition in an Integrated
      Dual Scan Analysis approach. The performance of both MS1 and MS2 data was
      examined in simple and complex samples using standard concentration curves. Cases
      of interferences in MS1 and MS2 ion intensity data were assessed, as were the
      differentiation and quantitation of phosphopeptide isomers in MS2 scan data. In
      addition, we demonstrated an approach for optimization of SWATH m/z window sizes
      to reduce interferences using MS1 scans as a guide. Finally, a correlation
      analysis was performed on both MS1 and MS2 ion intensity data obtained from SWATH
      acquisitions on a complex mixture using a linear model that automatically removes
      signals containing interferences. This work demonstrates the practical advantages
      of properly acquiring and processing MS1 precursor data in addition to MS2
      fragment ion intensity data in a data-independent acquisition (SWATH), and
      provides an approach to simultaneously obtain independent measurements of
      relative peptide abundance from a single experiment.

PMID- 25987417
TI  - Fatty acids as modulators of neutrophil recruitment, function and survival.
AB  - Neutrophils are well-known to act in the destruction of invading microorganisms.
      They have also been implicated in the activation of other immune cells including
      B- and T-lymphocytes and in the resolution of inflammation and tissue
      regeneration. Neutrophils are produced in the bone marrow and released into the
      circulation from where they migrate to tissues to perform their effector
      functions. Neutrophils are in constant contact with fatty acids that can modulate
      their function, activation and fate (survival or cell death) through different
      mechanisms. In this review, the effects of fatty acids pertaining to five
      classes, namely, long-chain saturated fatty acids (LCSFAs), short-chain fatty
      acids (SCFAs), and omega-3 (n-3), omega-6 (n-6) and omega-9 (n-9) unsaturated
      fatty acids, on neutrophils and the relevance of these effects for disease
      development are discussed. 

PMID- 25987418
TI  - Wnt signaling in atherosclerosis.
AB  - Atherosclerosis is a disease of the vascular wall that forms the basis for a
      large spectrum of pathologies of various organs and tissues. Although massive
      research efforts in the last decades have yielded valuable information about its
      underlying molecular mechanisms, this has not led to a translation into effective
      therapeutic interventions that can stop the progression or even can induce
      regression of atherosclerosis. This underscores the importance of investigations
      on the involvement of novel signaling pathways in the development and progression
      of this condition. In this review we focus on the role of Wnt signaling in
      atherosclerosis. Experimental evidence is presented that Wnt signaling is
      involved in many aspects of the development and progression of vascular lesions
      including endothelial dysfunction, macrophage activation and the proliferation
      and migration of vascular smooth muscle cells. Subsequently, we will discuss the
      role of Wnt signaling in myocardial infarction and stroke, two common pathologies
      resulting from the progression of atherosclerotic lesions towards an unstable
      phenotype. Despite the fact that the published data sometimes are ambiguous or
      even conflicting, a picture is emerging that an attenuation of Wnt signaling is
      beneficial for the cardiovascular system that is compromised by atherosclerosis. 

PMID- 25987419
TI  - Baropacing as a new option for treatment of resistant hypertension.
AB  - Electrical carotid baroreflex activation therapy is an emerging device-based
      treatment for patients with resistant hypertension. Its blood pressure lowering
      effect has been demonstrated in several animal and human studies, with prolonged
      effect over the long-term. The main mechanism of the blood pressure reduction
      during this therapy is by inhibition of the sympathetic outflow. Yet the question
      arises whether the inhibition of central sympathetic activity is sufficient to be
      the sole mechanism behind the sustained reduction in blood pressure. The major
      focus of this review is to elucidate the mechanisms of action that account for
      the effects of continuous carotid baroreflex activation on blood pressure in
      humans. Recent results of baroreflex activation therapy as a treatment for heart
      failure will also be discussed. 

PMID- 25987421
TI  - Functions of omega-3 fatty acids and FFA4 (GPR120) in macrophages.
AB  - Omega-3 polyunsaturated fatty acids (n-3 PUFAs), which are plentiful in fish oil,
      have been known for decades to be beneficial functional nutrients in different
      disease states. GPR120 is a G protein-coupled receptor for long-chain unsaturated
      fatty acids, including n-3 PUFAs, and was recently renamed free fatty acid
      receptor 4 (FFA4). Studies on FFA4-deficient mice and the development of specific
      pharmacological tools have started to unravel the functions of FFA4 associated
      with the actions of n-3 PUFAs in obesity, type 2 diabetes, and inflammation
      related diseases. Here, the state of the art regarding the roles and functions of
      FFA4 and n-3 PUFA in macrophages are reviewed from the pharmacological
      perspective. In particular, the functions of n-3 PUFA on the anti-inflammatory M2
      phenotypes of macrophages in different organs, such as, adipose tissues and
      liver, are discussed along with future research directions. 

PMID- 25987422
TI  - It is all about fluidity: Fatty acids and macrophage phagocytosis.
AB  - Phagocytosis is an early and fundamental step for the effective clearance of
      disease causing agents. The ability to engulf and kill pathogens is considered as
      a major effector function of macrophages. In their phagocytic role macrophages
      are part of the first line of innate immune defense. A number of studies
      investigating fatty acid effects on macrophage phagocytosis have been conducted
      over many years. In vitro-data consistently report that alterations in macrophage
      membrane fatty acid composition are linked to an altered phagocytic capacity,
      i.e. an increase in membrane unsaturated fatty acid content is associated with an
      increase in engulfment and killing rate. The mode of action of fatty acids seems
      to be the modulation of the physical nature of the macrophage plasma membrane. It
      appears that the saturated-to-unsaturated fatty acid ratio of macrophage membrane
      phospholipids is of importance in determining macrophage phagocytic capacity.
      Available in vivo-data are less clear. At present, there is a lack of systematic
      studies elucidating key factors such as fatty acid efficacy, effective dose or
      dosing intervals. Without this knowledge the targeted modulation of macrophage
      phagocytosis in vivo by fatty acids is still a distant possibility. 

PMID- 25987423
TI  - Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their
      role in inflammation associated with metabolic syndrome and cancer.
AB  - Linoleic acid (LA) is a major constituent of low-density lipoproteins. An
      essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by
      endogenous enzymes and reactive oxygen species in the circulation. Increased
      levels of low-density lipoproteins coupled with oxidative stress and lack of
      antioxidants drive the oxidative processes. This results in synthesis of a range
      of oxidised derivatives, which play a vital role in regulation of inflammatory
      processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo
      octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic
      acids. In this review, we examine the role of LA derivatives and their actions on
      regulation of inflammation relevant to metabolic processes associated with
      atherogenesis and cancer. The processes affected by LA derivatives include,
      alteration of airway smooth muscles and vascular wall, affecting sensitivity to
      pain, and regulating endogenous steroid hormones associated with metabolic
      syndrome. LA derivatives alter cell adhesion molecules, this initial step, is
      pivotal in regulating inflammatory processes involving transcription factor
      peroxisome proliferator-activated receptor pathways, thus, leading to alteration
      of metabolic processes. The derivatives are known to elicit pleiotropic effects
      that are either beneficial or detrimental in nature hence making it difficult to
      determine the exact role of these derivatives in the progress of an assumed
      target disorder. The key may lie in understanding the role of these derivatives
      at various stages of development of a disorder. Novel pharmacological approaches
      in altering the synthesis or introduction of synthesised LA derivatives could
      possibly help drive processes that could regulate inflammation in a beneficial
      manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9-
      hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic
      acid (PubChem CID: 6443013), 9-oxo-octadecadienoic acid (PubChem CID: 3083831),
      13-oxo-octadecadienoic acid (PubChem CID: 4163990), 9,10-epoxy-12-octadecenoate
      (PubChem CID: 5283018), 12,13-epoxy-9-keto-10- trans -octadecenoic acid (PubChem
      CID: 53394018), Pioglitazone (PubChem CID: 4829). 

PMID- 25987420
TI  - Mitochondrial fusion and fission proteins as novel therapeutic targets for
      treating cardiovascular disease.
AB  - The past decade has witnessed a number of exciting developments in the field of
      mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and
      movement impact on cellular physiology and pathology. By undergoing fusion and
      fission, mitochondria are able to change their morphology between elongated
      interconnected networks and discrete fragmented structures, respectively. The
      cardiac mitochondria, in particular, have garnered much interest due to their
      unique spatial arrangement in the adult cardiomyocyte, and the multiple roles
      they play in cell death and survival. In this article, we review the role of the
      mitochondrial fusion and fission proteins as novel therapeutic targets for
      treating cardiovascular disease. 

PMID- 25987424
TI  - Pro-resolving mediators produced from EPA and DHA: Overview of the pathways
      involved and their mechanisms in metabolic syndrome and related liver diseases.
AB  - A novel genus of pro-resolving lipid mediators endogenously generated from omega
      3 polyunsaturated fatty acids has been identified in exudates obtained during the
      resolution phase of acute inflammation. The term specialized pro-resolving
      mediators (SPM) has been coined for these lipid mediators, comprising four novel
      chemical mediator families designated resolvins of the E series (if derived from
      eicosapentaenoic acid) and resolvins of the D series, protectins and maresins (if
      generated from docosahexaenoic acid). These SPM act not only as "stop-signals" of
      inflammatory response, but also as facilitators of the ability of macrophages to
      clear apoptotic cells (efferocytosis) and migrate to peripheral lymph nodes
      (efflux), thus, expediting their removal from sites of inflammation. In this
      review, we provide an overview of the current efforts to elucidate the structure
      function, biosynthesis and actions of these omega-3-derived SPM in the context of
      inflammatory diseases. We specifically highlight the role of these SPM as
      endogenous counter-regulators of the persistent inflammatory status present in
      adipose tissue of obese individuals and describe the potential therapeutic impact
      of these bioactive lipid autacoids on the prevention of hepatic co-morbidities
      associated with obesity and the metabolic syndrome. 

PMID- 25987425
TI  - The renin-angiotensin system and its involvement in vascular disease.
AB  - The renin-angiotensin system (RAS) plays a critical role in the pathogenesis of
      many types of cardiovascular diseases including cardiomyopathy, valvular heart
      disease, aneurysms, stroke, coronary artery disease and vascular injury. Besides
      the classical regulatory effects on blood pressure and sodium homoeostasis, the
      RAS is involved in the regulation of contractility and remodelling of the vessel
      wall. Numerous studies have shown beneficial effect of inhibition of this system
      in the pathogenesis of cardiovascular diseases. However, dysregulation and
      overexpression of the RAS, through different molecular mechanisms, also induces,
      the initiation of vascular damage. The key effector peptide of the RAS,
      angiotensin II (Ang II) promotes cell proliferation, apoptosis, fibrosis,
      oxidative stress and inflammation, processes known to contribute to remodelling
      of the vasculature. In this review, we focus on the components that are under the
      influence of the RAS and contribute to the development and progression of
      vascular disease; extracellular matrix defects, atherosclerosis and ageing.
      Furthermore, the beneficial therapeutic effects of inhibition of the RAS on the
      vasculature are discussed, as well as the need for additive effects on top of RAS
      inhibition. 

PMID- 25987426
TI  - Modulation of inflammation and immunity by dietary conjugated linoleic acid.
AB  - Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers
      of linoleic acid. This family of polyunsaturated fatty acids has drawn
      significant attention in the last three decades for its variety of biologically
      beneficial properties and health effects. CLA has been shown to exert various
      potent protective functions such as anti-inflammatory, anticarcinogenic,
      antiadipogenic, antidiabetic and antihypertensive properties in animal models of
      disease. Therefore, CLA represents a nutritional avenue to prevent lifestyle
      diseases or metabolic syndrome. Initially, the overall effects of CLA were
      thought to be the result of interactions between its two major isomers: cis-9,
      trans-11 and trans-10, cis-12. However, later evidence suggests that such
      physiological effects of CLA might be different between the isomers: t-10, c-12
      CLA is thought to be anticarcinogenic, antiobesity and antidiabetic, whereas c-9,
      t-11-CLA is mainly anti-inflammatory. Although preclinical data support a benefit
      of CLA supplementation, human clinical findings have yet to show definitive
      evidence of a positive effect. The purpose of this review is to comprehensively
      summarize the mechanisms of action and anti-inflammatory properties of dietary
      CLA supplementation and evaluate the potential uses of CLA in human health and
      disease. 

PMID- 25987427
TI  - Inter-observer agreement for the evaluation of bone involvement on Whole Body Low
      Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM).
AB  - OBJECTIVE: We aimed to assess inter-observer agreement in bone involvement
      evaluation and define accuracy and reproducibility of MDCT images analysis in
      Multiple Myeloma (MM), by comparing two acquisition protocols at two different
      institutions. METHODS: A total of 100 MM patients underwent whole body low-dose
      computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV
      and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts)
      retrospectively reviewed 22 anatomical districts, reporting the following for
      each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4)
      risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous
      extension. Inter-observer agreement (by all readers, expert and young observers
      and comparison of the two protocols) was then statistically analyzed. RESULTS:
      According to Cohen's criteria, inter-observer agreement among the four readers
      and between experts and residents was good for the detection of bone lesions and
      extra-medullary extension, and for the evaluation of risk of collapse and
      cortical integrity. There was good agreement when comparing the two protocols. A
      greater variability was found for the evaluation of hyperattenuating lesions and
      the presence of fractures. CONCLUSIONS: WB-LDCT represents a reproducible and
      reliable technique that is helpful for defining bone disease in MM patients, with
      partial influence of readers' experience. KEY POINTS: * MDCT represents a
      reproducible technique for defining bone disease in MM. * Overall inter-observer
      agreement is good, even when comparing two different protocols. * Influence of
      readers' experience on image analysis is partial.

PMID- 25987428
TI  - Mammographic positioning quality of newly trained versus experienced
      radiographers in the Dutch breast cancer screening programme.
AB  - PURPOSE: Our purpose was to compare mammographic positioning quality of new (NR)
      versus experienced screening radiographers (ER) in the Netherlands. METHODS AND
      MATERIALS: Before starting to work in breast screening, NR must complete an
      education programme including a theoretical course (four days), practical
      training (six weeks), and a portfolio-review of 50 mammographic screening
      examinations performed by the radiographer. Furthermore, Dutch screening has an
      extensive system of quality assurance, including an audit-review of positioning
      quality of mammograms by ER. We analysed 13,520 portfolio views (NR) and 14,896
      audit views (ER) based on pre-specified criteria, e.g., depiction of inframammary
      angle. RESULTS: Overall positioning was more adequate for NR than ER (CC views:
      97% versus 86%, p = 0.00; MLO views: 92% versus 84%, p = 0.00). NR scored better
      for most of the CC-criteria and showed, for instance, less folds (inadequate: 10%
      versus 16%, p = 0.00). In contrast, NR encountered more difficulties for MLO
      views in, for example, depiction of infra-mammary angle (inadequate: 38% versus
      34%, p = 0.00). Overall, mammograms from NR were more often considered adequate,
      because of less severe errors. CONCLUSION: NR perform better than ER in overall
      positioning technique. These results stress the need for continuous monitoring
      and training in breast screening programmes to keep positioning skills up to
      date. KEY POINTS: * We evaluated positioning quality of new and experienced Dutch
      screening radiographers. * New radiographers outperform their experienced
      colleagues in mammographic positioning quality. * New radiographers make less
      severe errors compared to experienced colleagues. * There is a need for a
      continuous individual monitoring and feedback system.

PMID- 25987430
TI  - No more physician in physician-assisted suicide.

PMID- 25987432
TI  - Correction.
AB  - Feyi K, Klinger S, Pharro G et al. Predicting palliative care needs and mortality
      in end stage renal disease: use of an at-risk register. BMJ Support Palliat Care
      2015;5:19-25. The corresponding author's email address has been updated to
      s.klinger@nhs.net

PMID- 25987436
TI  - Acting out the past. Procedural/episodic memory dissociation in arts and media.

PMID- 25987435
TI  - Ancestral reconstruction of reproductive traits shows no tendency toward
      terrestriality in leptodactyline frogs.
AB  - BACKGROUND: Traditionally, the evolution of terrestrial reproduction in anurans
      from ancestors that bred in water has been accepted in the literature. Still, the
      existence of intermediate stages of water dependency, such as species that lay
      eggs close to water (e.g., in burrows) instead of in bodies of water, supports
      the hypothesis of an ordered and gradual evolution in the direction of a more
      terrestrial form of reproduction. However, this conventional view has recently
      been challenged for some anurans groups. Leptodactylinae frogs are a remarkable
      example of anurans with an outstanding diversity in terms of reproductive
      features, with distinct water dependency among lineages. Here, we tested the
      hypothesis of a gradual and ordered tendency towards terrestriality in
      Leptodactylinae, including the existence of obligatory intermediate stages, such
      as semi-terrestrial reproductive strategies. We also addressed the association
      between reproductive modes and the morphological and ecological features.
      RESULTS: An ancestral reconstruction analysis indicated that even though shifts
      from aquatic to terrestrial breeding occurred throughout the history of
      Leptodactylus and Adenomera, shifts from terrestrial to aquatic reproduction
      happened at almost the same frequency. Our results also demonstrated that
      reproductive modes for semi-terrestrial tadpoles were not necessarily an
      intermediate form between aquatic and terrestrial breeds. Correlations among
      reproductive modes and other life-history traits suggested that tadpole
      environment, clutch size, nuptial spines, and egg pigmentation were co-evolving
      and driven by water dependency. CONCLUSIONS: Our results found no evidence of
      evolutionary tendencies toward terrestriality in Leptodactylinae. We found
      reversals from terrestrial to aquatic tadpole development and no evidence of
      obligatory intermediate stages, such as semi-terrestrial reproductive strategies.
      We also found correlations between reproductive modes and other life-history
      traits driven by water dependence. Aquatic reproductive modes are associated with
      higher clutch sizes, lentic waters, and the presence of nuptial spines and egg
      pigmentation.

PMID- 25987437
TI  - Time for prediction? The effect of presentation rate on predictive sentence
      comprehension during word-by-word reading.
AB  - Predictive processing is a core component of normal language comprehension, but
      the brain may not engage in prediction to the same extent in all circumstances.
      This study investigates the effects of timing on anticipatory comprehension
      mechanisms. Event-related brain potentials (ERPs) were recorded while
      participants read two-sentence mini-scenarios previously shown to elicit
      prediction-related effects for implausible items that are categorically related
      to expected items ('They wanted to make the hotel look more like a tropical
      resort. So along the driveway they planted rows of PALMS/PINES/TULIPS.'). The
      first sentence of every pair was presented in its entirety and was self-paced.
      The second sentence was presented word-by-word with a fixed stimulus onset
      asynchrony (SOA) of either 500 msec or 250 msec that was manipulated in a within
      subjects blocked design. Amplitudes of the N400 ERP component are taken as a
      neural index of demands on semantic processing. At 500 msec SOA, implausible
      words related to predictable words elicited reduced N400 amplitudes compared to
      unrelated words (PINES vs TULIPS), replicating past studies. At 250 msec SOA this
      prediction-related semantic facilitation was diminished. Thus, timing is a factor
      in determining the extent to which anticipatory mechanisms are engaged. However,
      we found evidence that prediction can sometimes be engaged even under speeded
      presentation rates. Participants who first read sentences in the 250 msec SOA
      block showed no effect of semantic similarity for this SOA, although these same
      participants showed the effect in the second block with 500 msec SOA. However,
      participants who first read sentences in the 500 msec SOA block continued to show
      the N400 semantic similarity effect in the 250 msec SOA block. These findings add
      to results showing that the brain flexibly allocates resources to most
      effectively achieve comprehension goals given the current processing environment.

PMID- 25987438
TI  - Dissociated word production and comprehension in semantic dementia.

PMID- 25987440
TI  - Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of
      alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian
      population.
AB  - The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden
      506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian
      patients with liver cirrhosis, consecutively enrolled from June 2008 to January
      2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic
      factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively
      enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the
      above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT
      were the most frequent THRGFs, statistically significant in patients with
      alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28, 50 and 73,
      and 65 and 83 (all chi-square tests>3.84, and p values<0.05). Two logistic
      regression analysis, using PAI-1 4G-4G and MTHFR 677TT, as dependent variable,
      confirmed the independent significant relationship of these THRGFs with alcohol,
      cryptogenic liver cirrhosis and PVT. PAI 1 and MTHFR 677 genotypes, deviated from
      those expected in populations in Hardy-Weinberg equilibrium (all p values<0.05),
      in the subgroups of patients with alcohol, cryptogenic liver cirrhosis and
      presence of PVT. Our study shows the pivotal role of PAI-1 4G-4G and MTHFR 677TT
      in patients with alcohol, cryptogenic liver cirrhosis, and PVT, in a Caucasian
      population. In conclusion, thrombo and fibro-genetic mechanisms of PAI-1 4G-4G
      and MTHFR 677TT, could have a role in the development of liver cirrhosis, mainly
      in patients without HCV and HBV, and PVT.

PMID- 25987442
TI  - Reconsolidation and the regulation of plasticity: moving beyond memory.
AB  - Memory reconsolidation is a protein synthesis-dependent process that preserves,
      in some form, memories that have been destabilized through recall.
      Reconsolidation is a nearly universal phenomenon, occurring in a diverse array of
      species and learning tasks. The function of reconsolidation remains unclear but
      it has been proposed as a mechanism for updating or strengthening memories.
      Observations of an analog of reconsolidation in vitro and in sensory systems
      indicate that reconsolidation is unlikely to be a learning-specific phenomenon
      and may serve a broader function. We propose that reconsolidation arises from the
      activity-dependent induction of two coincident but opposing processes: the
      depotentiation and repotentiation of strengthened synapses. These processes
      suggest that reconsolidation reflects a fundamental mechanism that regulates and
      preserves synaptic strength. 

PMID- 25987441
TI  - The effects of antioxidant vitamin supplementation on expiratory flow rates at
      rest and during exercise.
AB  - PURPOSE: Previous studies suggest that pulmonary function is associated with
      fruit and vegetable consumption and plasma concentrations of antioxidant
      vitamins. Also, expiratory flow limitation (EFL) has been reported to limit
      ventilation during exercise in healthy individuals. We hypothesized antioxidant
      vitamin supplementation (AVS) would increase resting expiratory flow rates in
      healthy subjects and reduce EFL during exercise. METHODS: Ten healthy, nonsmoking
      subjects (5 M/5 W), consuming <5 servings of fruit and vegetables per day,
      participated in a randomized, single-blinded crossover design study with subjects
      receiving a placebo (PLA) or AVS [vitamins C (500 mg), E (400 IU), beta-carotene
      (15,000 IU), zinc (7.5 mg), selenium (50 mg), copper (1 mg), and manganese (2.5
      mg)] for 4 weeks. After a minimum 4-week washout period, subjects received the
      alternate supplementation. Pulmonary function tests and total antioxidant status
      (TAS) from plasma were measured pre- and post-supplement period. Subjects
      completed a pre- and post-supplement treadmill test for 20 min at 70% [Formula:
      see text] followed by increasing workload until exhaustion. RESULTS: AVS
      increased (p < 0.05) TAS by ~21% and resting expiratory flow rates (FEF25-75,
      FEF50) by ~9%. Following AVS, %EFL was significantly reduced by ~15% at minute
      15, 20, and end-exercise with no change (p > 0.05) in end-expiratory lung
      volumes. Breathing frequency and ratings of perceived exertion and dyspnea were
      also lower (p < 0.05) at min 20 of exercise. No changes (p > 0.05) were evident
      at rest or during exercise with PLA. CONCLUSIONS: These results suggest that AVS
      can increase TAS, improve resting expiratory flow rates and reduce EFL during
      exercise in healthy subjects who are not meeting fruit and vegetable
      recommendations.

PMID- 25987443
TI  - Embracing multiple definitions of learning.
AB  - Definitions of learning vary widely across disciplines, driven largely by
      different approaches used to assess its occurrence. These definitions can be
      better reconciled with each other if each is recognized as coherent with a common
      conceptualization of learning, while appreciating the practical utility of
      different learning definitions in different contexts. 

PMID- 25987444
TI  - [Pharmacotherapeutic care for vulnerable groups with polypharmacy has to get
      better].
AB  - Pharmacotherapeutic care of the elderly and psychiatric patients is complex and
      risky, because polypharmacy, the chronic use of five or more medications by a
      patient, is highly prevalent in these groups. Polypharmacy is a risk factor for
      medication related hospital admissions. The Dutch Health Care Inspectorate (IGZ)
      adopted 'improving care for the elderly' and 'improving medication safety' as
      spearheads. In order to provide input to IGZ enforcement policy, RIVM
      investigated the risks of polypharmacy as well as the measures that might limit
      these risks. This study shows that over- and undertreatment frequently occur.
      This may be caused by the fact that a physician sometimes does not know which
      medicines for a patient were prescribed, changed or stopped by other physicians.
      It was also found that psychiatric patients often experience side effects or
      interactions that are specific to psychiatric medicines, sometimes in combination
      with somatic medication. Various guidelines to improve medication safety are
      available, but several bottlenecks hamper the implementation, for example in the
      area of collaboration, direction and transfer of information on medication. But
      also ICT is insufficiently facilitating and physicians have too little knowledge
      of polypharmacy in the frail populations. The health care sector is taking
      various initiatives to remove bottlenecks. IGZ will from 2015 in all health care
      domains focus on four guidelines that describe the conditions for sensibly
      prescribing medication to frail people with polypharmacy. 

PMID- 25987445
TI  - [In Process Citation].

PMID- 25987446
TI  - Academic-industrial partnerships in drug discovery in the age of genomics.
AB  - Many US FDA-approved drugs have been developed through productive interactions
      between the biotechnology industry and academia. Technological breakthroughs in
      genomics, in particular large-scale sequencing of human genomes, is creating new
      opportunities to understand the biology of disease and to identify high-value
      targets relevant to a broad range of disorders. However, the scale of the work
      required to appropriately analyze large genomic and clinical data sets is
      challenging industry to develop a broader view of what areas of work constitute
      precompetitive research. 

PMID- 25987439
TI  - The biological functions of Naa10 - From amino-terminal acetylation to human
      disease.
AB  - N-terminal acetylation (NTA) is one of the most abundant protein modifications
      known, and the N-terminal acetyltransferase (NAT) machinery is conserved
      throughout all Eukarya. Over the past 50 years, the function of NTA has begun to
      be slowly elucidated, and this includes the modulation of protein-protein
      interaction, protein-stability, protein function, and protein targeting to
      specific cellular compartments. Many of these functions have been studied in the
      context of Naa10/NatA; however, we are only starting to really understand the
      full complexity of this picture. Roughly, about 40% of all human proteins are
      substrates of Naa10 and the impact of this modification has only been studied for
      a few of them. Besides acting as a NAT in the NatA complex, recently other
      functions have been linked to Naa10, including post-translational NTA, lysine
      acetylation, and NAT/KAT-independent functions. Also, recent publications have
      linked mutations in Naa10 to various diseases, emphasizing the importance of
      Naa10 research in humans. The recent design and synthesis of the first
      bisubstrate inhibitors that potently and selectively inhibit the NatA/Naa10
      complex, monomeric Naa10, and hNaa50 further increases the toolset to analyze
      Naa10 function.

PMID- 25987449
TI  - Local infiltration analgesia versus femoral nerve block in total knee
      arthroplasty: a meta-analysis.
AB  - INTRODUCTION: Local infiltration analgesia (LIA) and femoral nerve block (FNB)
      are both used for the pain management after total knee arthroplasty (TKA).
      Controversy still remains regarding the optimal technique for pain relief in
      patients undergoing TKA. The purpose of this meta-analysis was to compare the
      analgesia achieved with LIA and the one from FNB following TKA. HYPOTHESIS: LIA
      achieves better pain control than FNB in patients with TKA. METHODS: Databases,
      including Pubmed, EMBASE, the Cochrane Library and Web of Science were
      comprehensively searched to identify studies comparing LIA with FNB for patients
      with TKA. Two reviewers independently selected trials, extracted data, and
      assessed the methodological qualities of included studies. Data were analyzed by
      RevMan 5.2. RESULTS: Nine RCTs involving 782 patients were included. LIA achieved
      more rapid pain relief (VAS) at 6h postoperatively [SMD6h=-0.92, 95% CI (-1.38, 
      0.47)] than FNB. There were no significant differences at 24h and 48h [SMD24h=
      0.03, 95% CI (-0.46, 0.40); SMD48h=0.28, 95% CI (-0.35, 0.91)], VAS with activity
      at 24h and 48h [SMD6h=-0.54, 95% CI (-1.62, 0.54); SMD24h=-0.22, 95% CI (-1.41,
      0.96); SMD48h=-0.08, 95% CI (-0.52, 0.69)], opioid consumption at 24h and 48h
      [SMD24h=-0.24, 95% CI (-0.82, 0.34); SMD48h=0.15, 95% CI (0.25, 0.54)] and length
      of hospital stay [MD=-0.52, 95% CI (-1.13, 0.09)]. DISCUSSION: LIA may be the
      better choice in the pain management of TKA for it could achieve fast pain relief
      and is easier to perform than FNB for patients with TKA. LEVEL OF EVIDENCE: Level
      II, meta-analysis and systematic review.

PMID- 25987450
TI  - Flexible ureteroscopic laser lithotripsy for upper urinary tract stone disease in
      patients with spinal cord injury.
AB  - The objective of this study is to present the outcomes of flexible ureteroscopic
      laser lithotripsy (URS) for upper urinary tract stone disease in spinal cord
      injury (SCI) patients performed by a single surgeon. A retrospective analysis was
      performed for SCI patients treated with flexible URS for proximal ureter and
      kidney stone disease by a single surgeon between 2003 and 2013. Patient
      characteristics, operative outcomes, metabolic evaluation, and stone analyses
      were assessed in detail. A total of 27 URS procedures were performed for
      urolithiasis in 21 renal units of 19 patients. The mean age was 52.1 +/- 15.6
      years (16-72) and mean BMI was 29.2 +/- 7.3 kg/m(2) (20-45.7). Etiology of SCI
      was trauma (n: 10), multiple sclerosis (n: 6), cerebrovascular accident (n: 1),
      or undetermined (n: 2). The mean stone size was 15.9 +/- 8.6 (6-40) mm. In the 27
      URS procedures, stones were located in the ureter (n: 5), the kidney (n: 14), and
      both areas (n: 8). Mean hospitalization time was 2.0 +/- 2.4 (0-10) days.
      Postoperative complications were observed in 6 cases (22.2%). Three major
      complications included urosepsis (n: 1) and respiratory failure (n: 2), that were
      observed postoperatively and required admission to the intensive care unit. The 2
      minor complications were hypotension, fever and UTI, and required medical
      treatment. Fourteen (66.6%) of the 21 renal units were stone free. Calcium
      phosphate carbonate (n: 9) and struvite (n: 5) were the primary stone
      compositions detected. Hypocitraturia (n: 6), hypercalciuria (n: 5), hypernaturia
      (n: 5), hyperoxaluria (n: 4), and hyperuricosuria (n: 1) were common
      abnormalities in 24-h urine analysis. Ureteroscopic laser lithotripsy can be an
      effective treatment modality for SCI patients with upper urinary tract calculi.

PMID- 25987452
TI  - Late onset of progressive neurological deficits in severe angular kyphosis
      related to tuberculosis spondylitis.
AB  - PURPOSE: To investigate the causes of late-onset, progressive neurological
      deficits in patients with severe angular kyphosis caused by spondylitis secondary
      to tuberculosis (TB spondylitis). METHODS: From 2000 to 2011, 36 patients with
      severe angular kyphosis secondary to TB spondylitis (TB kyphosis) were enrolled
      in the study. All patients had late-onset, progressive neurological deficits. The
      causes of these deficits were classified with respect to the level of the
      causative lesion. Group A (n = 25, 69.4%) comprised patients whose neurological
      deficits resulted from the kyphosis itself. Patients in group B (n = 11, 30.6%)
      had developed neurological symptoms related to a lesion cephalad or caudal from
      the kyphosis. Surgical intervention was performed in 23 patients; 13 patients
      were treated conservatively. Clinical outcomes were evaluated using the American
      Spinal Injury Association (ASIA) impairment scale. RESULTS: The late onset of
      neurological deficits was attributed to cord compression, pure cord distraction,
      stenosis, and instability above or below the level of the angular kyphosis. An
      improvement of the neurological symptoms at the cord level after surgical
      intervention, as indicated by a change from a non-ambulatory (ASIA impairment
      scale A/C) to an ambulatory (ASIA D/E) status, occurred in four of nine (44.4%)
      surgically treated patients. However, only 2 of 10 (20.0%) patients treated
      conservatively showed cord level improvement, as assessed using the ASIA
      impairment scale. CONCLUSIONS: In their evaluation of paraplegic patients, spine
      surgeons should consider the many potential causes of late-onset neurological
      deficits in TB spondylitis to avoid performing unnecessary surgery. A simpler
      procedure may yield equivalent results.

PMID- 25987453
TI  - Answer to the Letter to the Editor of Marco A. Marino et al. concerning
      "Circumferential fusion using a custom-made screw in the management of high-grade
      spondylolisthesis" by Jouve JL, et al. (2014) Eur Spine J; 23(Suppl. 4):S457
      S462.

PMID- 25987454
TI  - Relationship between sedimentation sign and morphological grade in symptomatic
      lumbar spinal stenosis.
AB  - PURPOSE: We aimed to study the relationship between two morphological parameters
      recently described on MRI images in relation to lumbar spinal stenosis (LSS): the
      first is the sedimentation sign (SedS) and the second is the morphological
      grading of lumbar stenosis. MATERIALS AND METHODS: MRIs from a total of 137
      patients were studied. From those, 110 were issued from a prospective database of
      symptomatic LSS patients, of whom 73 were treated surgically and 37
      conservatively based on symptom severity. A third group consisting of 27 subjects
      complaining of low back pain (LBP) served as control. Severity of stenosis was
      judged at disc level using the four A to D grade morphological classification.
      The presence of a SedS was judged at pedicle level, above or below the site of
      maximal stenosis. RESULTS: A positive SedS was observed in 58, 69 and 76% of
      patients demonstrating B, C and D morphology, respectively, but in none with
      grade A morphology. The SedS was positive in 67 and 35% of the surgically and
      conservatively treated patients, respectively, and in 8% of the LBP group. C and
      D morphological grades were present in 97 and 35% of patients in the surgically
      and conservatively treated group, respectively, and in 18% of the LBP group.
      Presence of a positive SedS carried an increased risk of being submitted to
      surgery in the symptomatic LSS group (OR 3.5). This risk was even higher in the
      LSS patients demonstrating grade C or D morphology (OR 65). DISCUSSION AND
      CONCLUSION: One-third of surgically treated LSS patients do not present a SedS.
      This sign appears to be a lesser predictor of treatment modality in our setting
      of symptomatic LSS patients compared to the severity of stenosis judged by the
      morphological grade.

PMID- 25987455
TI  - Vertebral hemangiomas: their demographical characteristics, location along the
      spine and position within the vertebral body.
AB  - PURPOSE: Vertebral hemangiomas (VHs) are the most common form of benign tumors in
      the spine. The aim of this research was to study the prevalence of VHs in the
      human population, their distribution along the spine and their location in the
      vertebral body. METHODS: The presence of VHs was assessed in full spine CT scans
      of 196 adults. Demographic data were gathered from medical records. RESULTS: VHs
      were present in 26.0% of the individuals studied, a rate significantly higher
      (chi2=43.338, p<0.001) than the prevalence reported in the literature (10.7%).
      Multiple VHs (>=2) appeared in 7.2% of the population studied. VHs prevalence is
      sex-independent, appearing in 28.6% of females and 23.5% of males (chi2=0.663,
      p=0.416); and age-dependent: the mean age of affected individuals (65.8 years)
      was significantly higher (p<0.001) than unaffected individuals (56.2 years). VH
      size was also age-dependent (p=0.023). No vertebra was significantly more prone
      to be affected by a hemangioma. T11 and T12 show the highest prevalence of VHs
      (3.57% of vertebrae affected). VHs were found in similar percentages in the
      anterior and posterior parts of the vertebral body (52.8 vs. 47.2%,
      respectively); and at its center and periphery (50.1 and 49.9%, respectively).
      VHs usually appeared at mid-height of the vertebral body or slightly higher.
      CONCLUSIONS: The reported prevalence of VHs is dependent on the demographic
      structure of the population studied, the size of the VHs and the method used to
      identify them. Overall, the phenomenon is more frequent than usually reported.
      VHs may appear at all vertebral levels and in all areas of the vertebral body.

PMID- 25987456
TI  - Influence of cervical spine position on the radiographic parameters of the
      thoracic inlet alignment.
AB  - PURPOSE: Cervical sagittal balance is a complex phenomenon, influenced by many
      factors, which cannot be described by cervical lordosis alone. Attention has been
      focused on the relationship between T1 slope, thoracic inlet angle, and cervical
      sagittal balance. However, the effect of cervical position on these parameters
      has not been evaluated yet. The aim of this study was to assess the influence of
      cervical flexion and extension on radiographic thoracic inlet parameters.
      METHODS: 60 patients with one level radiculopathy symptoms underwent radiological
      examination. Mean age was 53 (40-72) years; there were 24 males and 34 females.
      Lateral standing X-rays of cervical spine were taken on the same day in neutral
      position, full flexion and full extension. Patients with previous cervical
      operations or congenital malformations were excluded. Thoracic inlet angle (TIA),
      neck tilt (NT) and thoracic (T1) slope were measured. Agreement between
      measurements was assessed and quantified by intra-class correlation coefficient
      (ICC) and median error for a single measurement (SEM). The ICC value greater than
      0.75 reflected sufficient agreement. RESULTS: The mean values of the parameters
      were: (1) for the neutral position: TIA 71.7 degrees  +/- 9.5 degrees ; T1 slope
      26.7 degrees  +/- 6.3 degrees ; and NT 44.9 degrees  +/- 7.2 degrees , (2) In
      extension: TIA 71.8 degrees  +/- 9.4 degrees ; T1 slope 24.9 degrees  +/- 7.6
      degrees ; and NT 46.9 degrees  +/- 7.2 degrees  and (3) In flexion 78.3 degrees 
      +/- 10.3 degrees ; T1 slope 33.6 degrees  +/- 7.8 degrees ; and NT 44.7 degrees 
      +/- 7.4 degrees . An excellent agreement was revealed for all NT measurements
      (ICC 0.76) and for TIA measured in flexion and neutral position (ICC 0.79). There
      was insufficient overall and in-pairs agreement for T1 slope measurements.
      CONCLUSIONS: Neck tilt measurements were not influenced by position of the
      cervical spine. T1 slope was significantly influenced by flexion and extension of
      the neck. This puts the concept that TIA is a morphologic parameter into
      question. This information should be taken into consideration when analyzing
      lateral radiographs of the cervical spine for clinical decision-making.

PMID- 25987457
TI  - Trust and Its Role in the Medical Encounter.
AB  - This paper addresses two research questions. The first is theoretical: What is
      trust? In the first half of this paper we present a distinctive tripartite
      analysis. We describe three attitudes, here called reliance, specific trust and
      general trust, each of which is characterised and illustrated. We argue that
      these attitudes are related, but not reducible, to one another. We suggest that
      the current impasse in the analysis of trust is in part due to the fact that some
      writers allude to these distinctions, but unclearly so, whilst others elide them
      altogether. The second research question focuses on doctor-patient interaction.
      Trust is often said to be central in medical encounters but this strikes us as
      too vague. The success of doctor-patient relations in part depends on adopting
      the most appropriate of the three attitudes we delineate. We argue that reliance
      is the appropriate attitude for most medical encounters. When circumstances do
      require trust, the distinction between specific trust and general trust is
      crucial. We describe medical encounters requiring specific trust. General trust
      is less often required in medicine; but it is appropriate in some cases and, when
      called for, it is called for strongly.

PMID- 25987458
TI  - A comprehensive genetic diagnosis of Chinese muscular dystrophy and congenital
      myopathy patients by targeted next-generation sequencing.
AB  - Muscular dystrophies and congenital myopathies are a large group of heterogeneous
      inherited muscle disorders. The spectrum of muscular dystrophies and congenital
      myopathies extends to more than 50 diseases today, even excluding the common
      forms Duchenne Muscular Dystrophy, Myotonic Dystrophy and Facioscapulohumeral
      Dystrophy. Unfortunately, even by critical clinical evaluation and muscle
      pathology, diagnosis is still difficult. To potentially remediate this
      difficulty, we applied a microarray-based targeted next-generation sequencing
      (NGS) technology to diagnose these patients. There were 55 consecutive unrelated
      patients who underwent the test, 36 of which (65%) were found to have a causative
      mutation. Our result shows the accuracy and efficiency of next-generation
      sequencing in clinical circumstances and reflects the features and relative
      distribution of inherited myopathies in the Chinese population. 

PMID- 25987459
TI  - Cutin from watermelon peels: A novel inducer for cutinase production and its
      physicochemical characterization.
AB  - Cutin a polymeric biological macromolecule made up of esterified polyacids which
      acts as an inducer of cutinase. The present work was based on screening and
      characterization of newer cutin source from the agro industrial wastes as
      inducers of cutinase production by Fusarium oxysporum MTCC 2480. Cutin isolated
      from peels of multi green colored watermelon (WMC) yielded 6.77 U/mL as compared
      to that 9.64 U/mL of cutinase using apple cutin. The FTIR and (13)C CP-MAS solid
      state NMR studies indicated the nature of WMC to be an aliphatic polyester of
      polyhydroxy fatty acids. A further FTIR spectroscopic study on dewaxed cutin
      confirmed that the ester linkages in WMC were completely hydrolyzed during
      submerged fermentation. GC-MS data clearly indicated the critical structural
      feature of WMC viz. hydroxyl groups at omega-position and middle of the fatty
      acid chain. The amorphous nature of WMC was confirmed by XRD. DSC of WMC showed
      two endothermic transition peaks, one broad appearing at 30-60  degrees C and
      other at 145  degrees C. Thermogravimetric analysis of WMC suggested it to be
      thermally stable up to 200  degrees C. This study warrants further work on using
      WMC as a substrate for fermentative production of cutinase.

PMID- 25987460
TI  - Hydrophobic surface functionalization of lignocellulosic jute fabrics by
      enzymatic grafting of octadecylamine.
AB  - Enzymatic grafting of synthetic molecules onto lignins provides a mild and eco
      friendly alternative for the functionalization of lignocellulosic materials. In
      this study, laccase-mediated grafting of octadecylamine (OA) onto lignin-rich
      jute fabrics was investigated for enhancing the surface hydrophobicity. First,
      the lignins in jute fabrics were isolated and analyzed in the macromolecular
      level by MALDI-TOF MS, (1)H NMR, (13)C NMR, and HSQC-NMR. Then, the surface of
      jute fabrics was characterized by FT-IR, XPS, and SEM. Subsequently, the nitrogen
      content of jute fabrics was determined by the micro-Kjeldahl method, and the
      grafting percentage (Gp) and grafting efficiency (GE) of the enzymatic reaction
      were calculated. Finally, the surface hydrophobicity of the jute fabrics was
      estimated by contact angle and wetting time measurements. The results indicate
      that the OA monomers were successfully grafted onto the lignin moieties on the
      jute fiber surface by laccase with Gp and GE values of 0.712% and 10.571%,
      respectively. Moreover, the modified jute fabrics via OA-grafting showed an
      increased wetting time of 18.5 min and a contact angle of 116.72 degrees ,
      indicating that the surface hydrophobicity of the jute fabrics increased after
      the enzymatic grafting modification with hydrophobic OA molecules.

PMID- 25987461
TI  - Alginate-okra gum blend beads of diclofenac sodium from aqueous template using
      ZnSO4 as a cross-linker.
AB  - Zinc (Zn(2+))-ion induced diclofenac sodium (DS)-loaded alginate-okra (Hibiscus
      esculentus) gum (OG) blend beads was successfully formulated through Zn(2+)-ion
      induced ionic-gelation cross-linking method in a complete aqueous environment.
      Effects of polymer-blend ratio and cross-linker concentration on drug
      encapsulation efficiency (DEE) and cumulative drug release at 8 h (R8h) were
      optimized by 3(2)-factorial design. The optimized formulation of Zn(2+)-ion
      induced DS-loaded alginate-OG beads demonstrated 89.27+/-3.58% of DEE and 43.73+/
      2.83% of R8h. The bead sizes were within 1.10+/-0.07 to 1.38+/-0.14 mm. The bead
      surface morphology was analyzed by SEM. The drug-polymer interaction in the
      optimized bead matrix was analyzed by FTIR and P-XRD. These beads exhibited
      sustained in vitro drug release over a prolonged period of 8h and followed
      controlled-release (zero-order) pattern with super case-II transport mechanism.
      The swelling and degradation of the optimized beads was influenced by the pH of
      test mediums, which might be suitable for intestinal drug delivery.

PMID- 25987462
TI  - Gum tragacanth dispersions: Particle size and rheological properties affected by
      high-shear homogenization.
AB  - The effect of high-shear homogenization on the rheological and particle size
      characteristics of three species of gum tragacanth (GT) was detected. Dispersions
      were subjected to 0-20 min treatment. Static light scattering techniques and
      rheological tests were used to study the effect of treatment. The results showed
      that the process caused a decrease in particle size parameters for all three
      species, but interestingly, the apparent viscosities increased. The highest
      increase of apparent viscosity was found for solutions containing Astragalus
      gossypinus, which possessed the highest insoluble fraction. The viscoelastic
      behaviors of dispersions were also significantly influenced by the process.
      Homogenization caused an increase in both G' and G", in all three species. The
      alterations seem to be highly dependent on GT species and structure. The results
      could be of high importance in the industry, since the process will lead to
      textural modifications of food products containing GT.

PMID- 25987463
TI  - Five biopsy specimens from the proximal part of the tumor reliably determine HER2
      protein expression status in gastric cancer.
AB  - BACKGROUND: National guidelines recommend trastuzumab for treatment of patients
      with metastatic HER2-positive gastric cancer (GC). There is currently no
      guideline indicating the number of biopsy specimens and the location from which
      they should be obtained to reliably determine the human epidermal growth factor
      receptor 2 (HER2) status in GC. The aim of this pilot study was (a) to quantify
      HER2-positive tumor cells in different tumor regions to assess the spatial
      heterogeneity of HER2 expression and (b) to establish the required number of
      biopsy specimens and the location from which they should be obtained within the
      tumor to achieve concordance between HER2 expression status in the biopsy
      specimens and the resection specimen. METHODS: HER2 expression was quantified in
      six different regions of 24 HER2-positive GC and in six virtual biopsy specimens
      from different luminal regions. Intratumoral regional heterogeneity and
      concordance between HER2 status in the biopsy specimens and the resection
      specimen were analyzed. RESULTS: HER2-positive cells were more frequent in the
      luminal tumor surface compared with deeper layers (p < 0.001). GCs with
      differentiated histological features were more commonly HER2 positive (p <
      0.001). Assessment of HER2 expression status in five biopsy specimens was
      sufficient to achieve 100 % concordance between the biopsy specimens and the
      resection specimen. CONCLUSIONS: This is the first study to suggest preferential
      HER2 positivity at the luminal surface in GC and to establish a minimum number of
      biopsy specimens needed to obtain a biopsy HER2 result which is identical to that
      from the whole tumor. Our study suggests that HER2 testing in five tumor
      containing endoscopic biopsy specimens from the proximal (oral) part of the tumor
      is advisable. The results from this pilot study require validation in a
      prospective study.

PMID- 25987464
TI  - Three Wzy polymerases are specific for particular forms of an internal linkage in
      otherwise identical O units.
AB  - The Wzx/Wzy-dependent pathway is the predominant pathway for O-antigen production
      in Gram-negative bacteria. The O-antigen repeat unit (O unit) is an
      oligosaccharide that is assembled at the cytoplasmic face of the membrane on
      undecaprenyl pyrophosphate. Wzx then flips it to the periplasmic face for
      polymerization by Wzy, which adds an O unit to the reducing end of a growing O
      unit polymer in each round of polymerization. Wzx and Wzy both exhibit enormous
      sequence diversity. It has recently been shown that, contrary to earlier reports,
      the efficiency of diverse Wzx forms can be significantly reduced by minor
      structural variations to their native O-unit substrate. However, details of Wzy
      substrate specificity remain unexplored. The closely related galactose-initiated
      Salmonella O antigens present a rare opportunity to address these matters. The D1
      and D2 O units differ only in an internal mannose-rhamnose linkage, and D3
      expresses both in the same chain. D1 and D2 polymerases were shown to be specific
      for O units with their respective alpha or beta configuration for the internal
      mannose-rhamnose linkage. The Wzy encoded by D3 gene cluster polymerizes only D1
      O units, and deleting the gene does not eliminate polymeric O antigen, both
      observations indicating the presence of an additional wzy gene. The levels of Wzx
      and Wzy substrate specificity will affect the ease with which new O units can
      evolve, and also our ability to modify O antigens, capsules or secreted
      polysaccharides by glyco-engineering, to generate novel polysaccharides, as the
      Wzx/Wzy-dependent pathway is responsible for much of the diversity. 

PMID- 25987465
TI  - Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor
      Agonists as PET Tracers for Pancreatic beta cell Imaging.
AB  - PURPOSE: Copper-64 (Cu-64) and Galium-68 (Ga-68) radiolabeled DO3A and NODA
      conjugates of exendin-4 were used for preclinical imaging of pancreatic beta
      cells via targeting of glucagon-like peptide-1 receptor (GLP-1R). PROCEDURES:
      DO3A-VS- and NODA-VS-tagged Cys(40)exendin-4 (DO3A-VS-Cys(40)-exendin-4 and NODA
      VS-Cys(40)-exendin-4, respectively) were labeled with Cu-64 and Ga-68 using
      standard techniques. Biodistribution and dynamic positron emission tomography
      (PET) were carried out in normal Sprague-Dawley (SD) rats. Ex vivo
      autoradiography imaging was conducted with freshly frozen pancreatic thin
      sections. RESULTS: DO3A-VS- and NODA-VS-Cys(40)-exendin-4 analogues were labeled
      with Cu-64 and Ga-68 to a specific activity of 518.7 +/- 3.7 Ci/mmol (19.19 +/-
      0.14 TBq/mmol) and radiochemical yield above 98 %. Biodistribution data
      demonstrated pancreatic uptake of 0.11 +/- 0.02 %ID/g for [(64)Cu]DO3A-VS-, 0.14
      +/- 0.02 %ID/g for [(64)Cu]NODA-VS-, 0.11 +/- 0.03 for [(68)Ga]DO3A-VS-, and 0.26
      +/- 0.03 for [(68)Ga]NODA-VS-Cys(40)-exendin-4. Excess exendin-4 and exendin-(9
      39)-amide displaced all four Cu-64 and Ga-68 labeled exendin-4 derivatives in
      blocking studies. CONCLUSIONS: [(64)Cu]/[(68)Ga]DO3A-VS-Cys(40)- and
      [(64)Cu]/[(68)Ga]NODA-VS-Cys(40)-exendin-4 can be used as PET imaging agents
      specific for GLP-1R expressed on beta cells. Here, we report the first evidence
      of pancreatic uptake visualized with exendin-4 derivative in a rat animal model
      via in vivo dynamic PET imaging.

PMID- 25987466
TI  - In Vivo Detection of miRNA Expression in Tumors Using an Activatable Nanosensor.
AB  - PURPOSE: The development of tools for the analysis of microRNA (miRNA) function
      in tumors can advance our diagnostic and prognostic capabilities. Here, we
      describe the development of technology for the profiling of miRNA expression in
      the tumors of live animals. PROCEDURES: The approach is based on miRNA
      nanosensors consisting of sensor oligonucleotides conjugated to magnetic
      nanoparticles for systemic delivery. Feasibility was demonstrated for the
      detection of miR-10b, implicated in epithelial to mesenchymal transition and the
      development of metastasis. The miR-10b nanosensor was tested in vivo in two mouse
      models of cancer. In the first model, mice were implanted subcutaneously with MDA
      MB-231-luc-D3H2LN tumors, in which miR-10b was inhibited. In the second model,
      mice were implanted bilaterally with metastatic MDA-MB-231 and nonmetastatic MCF
      7 cells. The nanosensors were injected intravenously, and fluorescence intensity
      in the tumors was monitored over time. RESULTS: We showed that the described
      nanosensors are capable of discriminating between tumors based on their
      expression of miR-10b. Radiant efficiency was higher in the miR-10b-active tumors
      than in the miR-10b-inhibited tumors and in the MDA-MB-231 tumors relative to the
      MCF-7 tumors. CONCLUSIONS: The described technology provides an important tool
      that could be used to answer questions about microRNA function in cancer.

PMID- 25987467
TI  - A default normal chest CT structured reporting field for coronary calcifications
      does not cause excessive false-negative reporting.
AB  - PURPOSE: The aim of this study was to compare the accuracy of coronary
      atherosclerosis reporting before and after the implementation of a structured
      reporting chest CT template. METHODS: A noncardiac, noncontrast chest CT
      structured reporting template was developed and mandated for department-wide use
      at a large academic center. The template included the statement "There are no
      coronary artery calcifications." All noncardiac, noncontrast chest CT
      examinations reported over 3 days, 1 month after template implementation
      (structured template group), and from a 3-day period 1 year prior (control group)
      were retrospectively collected. Final radiology reports were reviewed and
      designated positive or negative for coronary calcifications. CT images were
      reviewed in consensus by 2 radiologists, who scored each case for the presence or
      absence of coronary calcifications, blinded to the original report. Statistical
      analysis was performed using Pearson chi(2) and Fisher exact tests. RESULTS:
      Sixty-five percent (69 of 106) of structured template group and 58% (62 of 106)
      of control group cases had coronary calcifications. Reports from the structured
      template group were more likely to correctly state the presence or absence of
      coronary atherosclerosis compared with those from the control group (96.2% vs
      85.8%; odds ratio, 4.2; 95% confidence interval, 1.3-13.1; P = .008). Structured
      template group reports were less likely to be falsely negative compared with
      control group reports (3.8% vs 11.7%; odds ratio, 3.4; 95% confidence interval,
      1.0-10.8; P = .03). CONCLUSIONS: Implementing a structured reporting template
      improves reporting accuracy of coronary calcifications.

PMID- 25987468
TI  - A Case for Radiology Analytics: Evidence Without Emotion.

PMID- 25987469
TI  - Cardiometabolic risks profile of normal weight obese and multi-ethnic women in a
      developing country.
AB  - OBJECTIVES: To determine the prevalence of normal weight obesity among multi
      ethnic women in Peninsular Malaysia and examine its associations with
      cardiometabolic risks and lifestyle behaviours. METHODS: This was a cross
      sectional study involving women recruited via multi-stage sampling from six
      states in Malaysia. Anthropometric and body composition analysis were performed.
      Normal weight obese (NWO) was defined as normal body mass index for Asians and
      the highest tertile of % body fat (BF). Biochemical measurements included fasting
      lipid and blood glucose levels. Metabolic syndrome was diagnosed based on the
      Harmonization criteria. Participants completed self-reported questionnaires that
      included physical activity, smoking, alcohol consumption, fruit and vegetable
      intake and sleep duration. MAIN OUTCOME MEASURE: Body mass index, %BF,
      cardiometabolic risk factors, lifestyle behaviours. RESULTS: A total of 6854
      women were recruited and the prevalence of NWO was 19.8% (95% CI: 17.3-22.5). NWO
      was more prevalent among the Indians and older women. NWO women had higher odds
      for abdominal obesity (OR: 2.64, 95% CI: 1.73-4.04), hypertriglyceridemia (2.51,
      1.47-4.29) and hypertension (1.63, 1.15-2.31) compared to women with lower % body
      fat after adjusted for age and ethnicity. The prevalence of metabolic syndrome
      among NWO women was 5.4% (95% CI: 3.0-9.8). None of the lifestyle behaviours were
      significantly associated with NWO. CONCLUSIONS: Women with NWO had
      cardiometabolic abnormalities including abdominal obesity, dyslipidaemia and
      increased blood pressure. Health promotion efforts should include NWO women who
      may be oblivious of their deleterious health risks.

PMID- 25987470
TI  - Nutlin-3 loaded nanocarriers: Preparation, characterization and in vitro
      antineoplastic effect against primary effusion lymphoma.
AB  - In this investigation, Nutlin-3 (Nut3), a novel antitumor drug with low water
      solubility (<0.1mg/L at 25 degrees C), was loaded into liposomes (Lipo-Nut3),
      polymeric nanoparticles (NPs-Nut3) and nanoparticles engineered with an antibody
      direct against Syndecan-1/CD 138 (Syn-NPs-Nut3) to obtain carriers targeted to
      PEL (primary effusion lymphoma). The physicochemical properties of these carriers
      were determined. Atomic force microscopy showed that all the particles were well
      formed and spherical in shape. The presence of the antibody on surface led to a
      significant increase of mean diameter (280 +/- 63 nm), PDI (0.3) and the shift of
      zeta potential towards neutrality (-1 mV). The entrapment efficiency of Lipo
      Nut3, NPs-Nut3 and Syn-NPs-Nut3 was 30, 52 and 29%, and drug loading was 1.4, 4.5
      and 2.6%, respectively. By performing cytofluorimetric analyses and
      bromodeoxyuridine (BrdU) assay, the efficacy of nanocarriers to deliver the
      antineoplastic drug into a PEL cell line namely BCBL-1 (immortalized body cavity
      B-cell lymphoma) was investigated. Two days after the treatment with 20 MUM of
      Syn-NPs-Nut3, the cell density decreased at about 60% while the cell viability
      decreased at 56% only 5 days after transfection, when compared with untreated
      cells. A cell cycle arrest was observed with a significant decrease of cells in S
      phase and increasing of apoptotic cell, if compared with untreated control. These
      results confirms the potential of nanocarriers approaches to deliver antitumor
      drug with unfavorable chemico-physical properties. Moreover, this study strongly
      suggests that Syn-NPs-Nut3 can be a valuable drug carrier system for the
      treatment of PEL lymphoma.

PMID- 25987471
TI  - Disparities in Quality of Healthcare of Children from Immigrant Families in the
      US.
AB  - The objective of this study was to examine disparities in quality of pediatric
      primary care among children from immigrant families in the US. Drawing from a
      nationally representative sample of 83,528 children ages 0-17 years from the 2007
      National Survey of Children's Health, weighted logistic regression was used to
      assess the effect of immigrant family type on five indicators of quality of
      healthcare across children's racial/ethnic groups. Analyses controlled for
      indicators of child's access to care, family socio-economic characteristics, and
      primary language spoken in the household. Unadjusted estimates revealed a pattern
      of decreasing disparities from immigrant children to second-generation children,
      native-born children of immigrant parents, and to third-generation children,
      native-born children of native-born parents. Controlling for confounders showed
      that the positive effect of generational status on the quality of healthcare of
      children from immigrant families varied across indicators and among racial/ethnic
      groups. Not even third-generation Hispanic and Black children reached parity with
      third-generation White children on reported amount of time that providers devoted
      to their care and on providers' sensitivity to their family's values and customs.
      In contrast, disparities in reports of providers listening carefully to
      caregivers disappeared after adjusting for confounders, and only families headed
      by immigrant parents reported receiving less specific health-related information
      than the families of native-born White children. Our study suggests that it is
      important to develop interventions that help healthcare professionals to learn
      how different types of immigrant families perceive the interactions with the
      healthcare system and how to deliver care that increases the satisfaction of
      children from different racial/ethnic groups.

PMID- 25987472
TI  - Biosimilars in Dermatology: Current Situation (Part I).
AB  - The first biosimilar version of a biologic agent used to treat psoriasis
      (infliximab) entered the Spanish market on February 16 of this year, and more
      biosimilars can be expected to follow in the coming months and years. Logically,
      this new situation will have economic repercussions and alter prescribing
      patterns among dermatologists. In this article, we review regulatory issues
      related to the approval of biosimilars, with a particular focus on the situation
      in the European Union. We will examine analytical characterization studies and
      special considerations for clinical trials with biosimilars, and also look at
      several somewhat contentious issues, such as the extrapolation of indications,
      interchangeability, and automatic substitution. Finally, we will review the
      biosimilars with indications for psoriasis currently in the clinical development
      pipeline and assess their potential to offer comparable efficacy and safety to
      the reference product while contributing to the sustainability of the public
      health care system. 

PMID- 25987473
TI  - Reverse capillary flow of condensed water through aligned multiwalled carbon
      nanotubes.
AB  - Molecular transport through nanopores has recently received considerable
      attention as a result of advances in nanofabrication and nanomaterial synthesis
      technologies. Surprisingly, water transport investigations through carbon
      nanochannels resulted in two contradicting observations: extremely fast transport
      or rejection of water molecules. In this paper, we elucidate the mechanism of
      impeded water vapor transport through the interstitial space of aligned
      multiwalled carbon nanotubes (aligned-MWCNTs)--capillary condensation,
      agglomeration, reverse capillary flow, and removal by superhydrophobicity at the
      tip of the nanotubes. The origin of separation comes from the water's phase
      change from gas to liquid, followed by reverse capillary flow. First, the
      saturation water vapor pressure is decreased in a confined space, which is
      favorable for the phase change of incoming water vapor into liquid drops. Once
      continuous water meniscus is formed between the nanotubes by the adsoprtion and
      agglomeration of water molecules, a high reverse Laplace pressure is induced in
      the mushroom-shaped liquid meniscus at the entry region of the aligned-MWCNTs.
      The reverse Laplace pressure can be significantly enhanced by decreasing the pore
      size. Finally, the droplets pushed backward by the reverse Laplace pressure can
      be removed by superhydrophobicity at the tip of the aligned-MWCNTs. The
      analytical analysis was also supported by experiments carried out using 4 mm-long
      aligned-MWCNTs with different intertube distances. The water rejection rate and
      the separation factor increased as the intertube distance decreased, resulting in
      90% and 10, respectively, at an intertube distance of 4 nm. This mechanism and
      nanotube membrane may be useful for energy-efficient water vapor separation and
      dehumidification.

PMID- 25987474
TI  - Corrigendum: Hsp90 facilitates accurate loading of precursor piRNAs into PIWI
      proteins.

PMID- 25987475
TI  - The correlation between seasonality and peripherally inserted central catheter
      related infections in cancer patients.

PMID- 25987476
TI  - Polybrominated diphenyl ethers in articles: a review of its applications and
      legislation.
AB  - Polybrominated diphenyl ethers (PBDEs), especially commercial decabrominated
      diphenyl ethers (c-decaBDE), have been widely produced and applied to numerous
      materials because of their highly effective flame-retardant capabilities. The
      production of commercial pentaBDE (c-pentaBDE) and commercial octaBDE (c-octaBDE)
      ended in 2004 because they are persistent, bioaccumulative, and toxic to both
      humans and the environment, but decaBDE production and use continue. Furthermore,
      many congeners of PBDEs are still prevalent in consumer products and articles
      that they pose enormous threat to both the environment and human health. PBDEs
      have been detected in the casing of electrical and electronic equipment, textile
      materials, automotive interiors, polyurethane foam (PUF) in seat cushions,
      children's toys, kitchenware, and other products. With increasing evidence about
      PBDE pollution and the adoption of international conventions, many developed
      countries have drawn more public attention to PBDEs and developed sound
      strategies for their management. This review summaries the utilization and
      management of PBDEs in a number of countries and reaches the conclusion that
      PBDEs are still prevalent in consumer articles, while specific regulations or
      policies for articles containing PBDEs are rare. Public awareness should be
      raised on the importance of sound management of articles containing PBDEs.

PMID- 25987477
TI  - Evaluation of zinc accumulation, allocation, and tolerance in Zea mays L.
      seedlings: implication for zinc phytoextraction.
AB  - This work investigated the accumulation, allocation, and impact of zinc (Zn; 1.0
      MUM-10 mM) in maize (Zea mays L.) seedlings under simulated laboratory
      conditions. Z. mays exhibited no significant change in its habitus (the physical
      characteristics of plants) up to 10-1000 MUM of Zn (vs 5-10 mM Zn). Zn tolerance
      evaluation, based on the root test, indicated a high tolerance of Z. mays to both
      low and intermediate (or relatively high) concentrations of Zn, whereas this
      plant failed to tolerate 10 mM Zn and exhibited a 5-fold decrease in its Zn
      tolerance. Contingent to Zn treatment levels, Zn hampered the growth of axial
      organs and brought decreases in the leaf area, water regime, and biomass
      accumulation. Nevertheless, at elevated levels of Zn (10 mM), Zn(2+) was stored
      in the root cytoplasm and inhibited both axial organ growth and water regime.
      However, accumulation and allocation of Zn in Z. mays roots, studied herein
      employing X-ray fluorimeter and histochemical methods, were close to Zn
      accumulator plants. Overall, the study outcomes revealed Zn tolerance of Z. mays,
      and also implicate its potential role in Zn phytoextraction.

PMID- 25987478
TI  - A pospiviroid from symptomless portulaca plants closely related to iresine viroid
      1.
AB  - In symptomless plants of portulaca a potential new pospiviroid was characterized.
      Analysis by both double and return PAGE showed the presence of a circular RNA. RT
      PCR and sequencing revealed a genome of 351 nt with properties characteristic of
      members of the genus Pospiviroid and with highest sequence identity (circa 80%)
      with iresine viroid 1 (IrVd-1). The circular RNA from portulaca was shown to
      replicate independently in its original host, thus showing that it is indeed a
      viroid. Based on its molecular characteristics, it should be considered a new
      species. However, since no biological differences have yet been found with its
      closest relative IrVd-1, the viroid from portulaca does not fulfil all criteria
      for species demarcation of the ICTV. 

PMID- 25987479
TI  - Severe leptospirosis complicated by Epstein-Barr Virus reactivation.
AB  - INTRODUCTION: Weil's disease is a severe, potentially fatal illness following
      Leptospira interrogans infection. The reported case of a patient suffering from
      acute renal failure, jaundice, thrombocytopenia, rhabdomyolysis and encephalitis
      syndrome highlights the clinical challenge in reference to Weil syndrome
      complicated by Epstein-Barr Virus (EBV) reactivation. MATERIALS AND METHODS: The
      diagnosis of leptospirosis was performed using four different diagnostic methods.
      Sera were analyzed with an in-house IgM and IgG enzyme-linked immunosorbent assay
      (ELISA) and indirect haemagglutination assay (IHA). Microscopic agglutination
      test (MAT) was done using 17 reference strains comprising 14 serogroups and 17
      serovars. Polyvalent EBV-IgG analysis, EBV-IgG/IgM/IgA western blot analysis as
      well as quantitative EBV polymerase chain reaction (PCR) were performed. RESULTS:
      Leptospira IHA showed an initial titer of 1:640 (cut-off 1:320), leptospiral IgG
      was negative, but IgM was positive. MAT was negative at that time for all 17
      strains analyzed. One week later, leptospirosis IHA titer increased to 1:20,480.
      Leptospiral IgG was now positive, -IgM remained positive and urine was tested
      negative for leptospiral DNA. The MAT showed positive results for L. interrogans
      serovar Bataviae, serovar Copenhageni, serovar Pyrogenes and L. borgpetersenii
      serovar Serjoe. During follow-up examinations, both the leptospiral IgM and IgG
      remained positive and MAT showed positive results for L. interrogans of different
      serovars. EBV IgA immunoblot taken at admission was positive for VCA-p18,
      quantitative EBV-PCR showed an EBV viral load of 2.8E3 copies/ml indicating acute
      EBV-reactivation. CONCLUSION: Leptospirosis represents a neglected and re
      emerging disease which is difficult to diagnose since Leptospira-PCR from whole
      blood or urine is frequently negative in the case of early empiric antibiotic
      treatment. EBV-reactivation might represent a severe complication in Weil's
      disease which potentially aggravates clinical manifestations of leptospirosis
      including hepatitis, nephritis, and rhabdomyolysis. Thus, there might be a need
      for peripheral blood EBV-PCR and EBV blotting in patients suffering from
      complicated Weil syndrome, also in terms of the choice of antibiotic treatment.

PMID- 25987481
TI  - Allele-specific analysis of DNA replication origins in mammalian cells.
AB  - The mechanisms that control the location and timing of firing of replication
      origins are poorly understood. Using a novel functional genomic approach based on
      the analysis of SNPs and indels in phased human genomes, we observe that
      replication asynchrony is associated with small cumulative variations in the
      initiation efficiency of multiple origins between the chromosome homologues,
      rather than with the activation of dormant origins. Allele-specific measurements
      demonstrate that the presence of G-quadruplex-forming sequences does not
      correlate with the efficiency of initiation. Sequence analysis reveals that the
      origins are highly enriched in sequences with profoundly asymmetric G/C and A/T
      nucleotide distributions and are almost completely depleted of antiparallel
      triplex-forming sequences. We therefore propose that although G4-forming
      sequences are abundant in replication origins, an asymmetry in nucleotide
      distribution, which increases the propensity of origins to unwind and adopt non-B
      DNA structure, rather than the ability to form G4, is directly associated with
      origin activity. 

PMID- 25987482
TI  - Rationale and study protocol for a two-part intervention: Safety planning and
      structured follow-up among veterans at risk for suicide and discharged from the
      emergency department.
AB  - There are no evidence-based, brief interventions to reduce suicide risk in
      Veterans. Death by suicide is a major public health problem. This article
      describes a protocol, Suicide Assessment and Follow-up Engagement: Veteran
      Emergency Treatment [SAFE VET], developed for testing the effectiveness of a
      brief intervention combining a Safety Planning Intervention with structured
      follow-up (SPI-SFU) to reduce near-term suicide risk and increase outpatient
      behavioral health treatment engagement among Veterans seeking treatment at
      Veteran Affairs Medical Center (VAMC) emergency departments (EDs) who are at risk
      for suicide. In addition to describing study procedures, outcome measures,
      primary and secondary hypotheses, and human subjects' protection issues, the
      rationale for the selection of SPI-SFU as the intervention is detailed, as are
      safety considerations for the unique study setting and sample. 

PMID- 25987480
TI  - Ageing with HIV: a multidisciplinary review.
AB  - INTRODUCTION: After the introduction of highly active antiretroviral treatment,
      the course of HIV infection turned into a chronic disease and most of HIV
      positive patients will soon be over 50 years old. MATERIAL AND METHODS: This
      paper reviews the multiple aspects that physicians have to face while taking care
      of HIV-positive ageing patients including the definitions of frailty and the
      prevalence and risk factors of concomitant diseases. From a therapeutic point of
      view pharmacokinetic changes and antiretroviral-specific toxicities associated
      with ageing are discussed; finally therapeutic approaches to frailty are reviewed
      both in HIV-positive and negative patients. CONCLUSION AND DISCUSSION: We
      conclude by suggesting that the combined use of drugs with the least toxicity
      potential and the promotion of healthy behaviours (including appropriate
      nutrition and exercise) might be the best practice for ageing HIV-positive
      subjects.

PMID- 25987484
TI  - Selecting control interventions for use in orthotic trials: The methodological
      benefits of sham orthoses.

PMID- 25987485
TI  - Femtosecond laser induced hierarchical ZnO superhydrophobic surfaces with
      switchable wettability.
AB  - A simple and one-step method to form a rough ZnO layer consisting of
      micro/nanoscale hierarchical structures via direct femtosecond laser ablation of
      the Zn surface is reported for the first time. The resultant surfaces show
      switchable wettability between superhydrophobicity and quasi-superhydrophilicity
      via alternate UV irradiation and dark storage. 

PMID- 25987483
TI  - Investigating within-day and longitudinal effects of maternal stress on
      children's physical activity, dietary intake, and body composition: Protocol for
      the MATCH study.
AB  - Parental stress is an understudied factor that may compromise parenting practices
      related to children's dietary intake, physical activity, and obesity. However,
      studies examining these associations have been subject to methodological
      limitations, including cross-sectional designs, retrospective measures, a lack of
      stress biomarkers, and the tendency to overlook momentary etiologic processes
      occurring within each day. This paper describes the recruitment, data collection,
      and data analytic protocols for the MATCH (Mothers And Their Children's Health)
      study, a longitudinal investigation using novel real-time data capture strategies
      to examine within-day associations of maternal stress with children's physical
      activity and dietary intake, and how these effects contribute to children's
      obesity risk. In the MATCH study, 200 mothers and their 8 to 12 year-old children
      are participating in 6 semi-annual assessment waves across 3 years. At each wave,
      measures for mother-child dyads include: (a) real-time Ecological Momentary
      Assessment (EMA) of self-reported daily psychosocial stressors (e.g., work at a
      job, family demands), feeling stressed, perceived stress, parenting practices,
      dietary intake, and physical activity with time and location stamps; (b) diurnal
      salivary cortisol patterns, accelerometer-monitored physical activity, and 24
      hour dietary recalls; (c) retrospective questionnaires of sociodemographic,
      cultural, family, and neighborhood covariates; and (d) height, weight, and waist
      circumference. Putative within-day and longitudinal effects of maternal stress on
      children's dietary intake, physical activity, and body composition will be tested
      through multilevel modeling and latent growth curve models, respectively. The
      results will inform interventions that help mothers reduce the negative effects
      of stress on weight-related parenting practices and children's obesity risk.

PMID- 25987486
TI  - Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1
      activities in non-small cell lung cancer tissue.
AB  - Topoisomerase I (TOP1) regulates DNA topology during replication and
      transcription whereas tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in the
      repair of several types of DNA damages, including damages from defective TOP1
      catalysis. TOP1 is the target of chemotherapeutic drugs of the camptothecin
      family (CPT). TDP1 has in cell line based assays been shown to counteract the
      effect of CPT. We have quantified the enzymatic activities of TOP1 and TDP1 in
      paired (tumor and adjacent non-tumor) samples from non-small cell lung cancer
      (NSCLC) patients and show that in NSCLC TOP1 and TDP1 activities are
      significantly upregulated in the tumor tissue. Furthermore, we found a positive
      correlation between the TDP1 activity and the tumor percentage (TOP1 activity did
      not correlate with the tumor percentage) as well as between the activities of
      TOP1 and TDP1 both within the tumor and the non-tumor group. That TDP1 activity
      was upregulated in all tumor samples and correlated with the tumor percentage
      suggest that it must play a highly important function in NSCLC. This could be to
      protect against TOP1 mediated DNA damage as the activity of TOP1 likewise was
      upregulated in the majority of tumor samples and correlated positively to the
      TDP1 activity. Regardless, the finding that the TOP1 and TDP1 activities are
      upregulated and correlate positively suggests that combinatorial treatment
      targeting both activities could be advantageous in NSCLC.

PMID- 25987487
TI  - Dietary inflammation potential and postmenopausal breast cancer risk in a German
      case-control study.
AB  - Unhealthy dietary habits can increase the risk for serious medical conditions,
      such as cancer, yet the association between diet and breast cancer remains
      unclear. We investigated whether individual diets based on their inflammatory
      potential are associated with postmenopausal breast cancer risk by employing an
      energy-adjusted dietary inflammation index. In a German population-based case
      control study, 2887 postmenopausal breast cancer patients (aged 50-74 years,
      first diagnosed between 2002 and 2005) and 5512 healthy age-matched controls
      provided information on dietary habits for the year prior to diagnosis (cases) or
      recruitment (controls) using a 176-items food frequency questionnaire.
      Associations between the energy-adjusted dietary inflammation index (E-DII) score
      (both as continuous variable and in quintiles) and risk for breast cancer were
      assessed using conditional logistic regression adjusted for potential
      confounders. No significant associations between the E-DII score and
      postmenopausal breast cancer risk were observed (adjusted OR Q5 vs Q1: 1.01, 95%
      CI: 0.86-1.17). Associations did not differ by estrogen receptor/progesterone
      receptor status (ER + PR+: adjusted OR Q5 vs Q1: 1.06, 95% CI: 0.88-1.27; ER + or
      PR+: OR Q5 vs Q1: 1,07, 95% CI: 0.79-1.45; ER-PR-: OR Q5 vs Q1: 0.87 95% CI: 0.63
      1.20). Our results regarding E-DII are consistent with previous studies reporting
      a lack of association between C-reactive protein, a marker of systemic
      inflammation, and postmenopausal breast cancer risk. The findings may reflect a
      real absence of association between dietary inflammatory potential and
      postmenopausal cancer risk or an underestimation of association due to recall
      bias. Further investigation is warranted in cohort studies.

PMID- 25987488
TI  - Translating the concept of intrinsic subtypes into an oncoplastic cohort of more
      than 1000 patients - predictors of recurrence and survival.
AB  - INTRODUCTION: A paradigm shift in breast cancer was introduced by Sorlie's
      concept of intrinsic subtypes [1]. We validated this concept - which was
      originally based on 84 individuals - in a large cohort study of 1035 patients
      with oncoplastic surgery and analyzed if early and late recurrences are linked to
      a specific intrinsic tumor subtype or resection margins. MATERIALS AND METHODS:
      1035 patients with oncoplastic surgery (2004-2009) were analyzed with regard to
      treatment characteristics and patterns of early (<5 years) and late recurrence
      (>5 years) and survival related to the intrinsic subtypes. Data was retrieved
      from patient's charts, customized patients questionnaires and cancer registries.
      RESULTS: 944 patients with primary, unilateral breast cancer, median age 58
      years, were eligible for analysis. At a median FU of 5.2 years, LRR was 4.0%, 5
      year-OS 94.5% and DFS 90.9%. Intrinsic subtypes, but not T-size, nodal-status,
      resections margins nor histopathology, governed local control and survival. There
      was no signal for prevelance of unclear margins in any of intrinsic subgroups and
      no preference of any oncoplastic technique attributed to them. TNBC and Her2 non
      luminal breast cancer had highest recurrence and lowest survival rates. Although
      sentinel involvement (SLN+) was prevailing in the Luminal-B-Her 2 negative
      subtype at 34.3%, this did not translate into a higher axillary dissection rate.
      CONCLUSION: This study confirmed the intrinsic subtype concept on a large
      clinical basis and describes the patterns of early and late recurrence in
      oncoplastic surgery, concluding that bigger risk may not be overcome by bigger
      surgery.

PMID- 25987490
TI  - "I Liked Girls and I Thought They Were Pretty": Initial Memories of Same-Sex
      Attraction in Young Lesbian and Bisexual Women.
AB  - There is little research on what is meant by the concept of "feeling attracted"
      and even less about what same-sex attraction looks and feels like for
      individuals. Without insight into the phenomenon of same-sex attraction,
      researchers risk misunderstanding the role of sexual attraction in sexual
      identity development and risk mis-categorizing individuals in research designs
      that compare LGBTQ and heterosexual samples. The current study draws from semi
      structured interviews (n = 30) with young lesbian-, bisexual-, and queer
      identified women (ages 18-24) about their initial memories of same-sex
      attraction. Two questions were pursued using qualitative analytic strategies. We
      examined the age that participants remembered first experiencing same-sex
      attraction using content analysis. Two age groups emerged as distinct: those with
      experiences of same-sex attraction in childhood and those with initial
      attractions in later adolescence. We also examined key elements in participants'
      descriptions of early same-sex attraction using thematic analysis. The role of
      embodied feelings, relationships with other young women, and social environments
      including media images emerged as central to initial experiences of attraction.
      Findings highlight how early experiences of same-sex attraction produced
      different types of interpretations within individuals and, in turn, these
      interpretations informed how participants did or did not take up LGBTQ identity
      labels. These findings may help guide the development of more refined measurement
      tools for researchers hoping to sample sexual minorities and can contribute to
      developing more effective supports for individuals who experience same-sex
      attraction but may not adopt LGBTQ identity labels and, as a result, are
      routinely missed in outreach efforts.

PMID- 25987489
TI  - Dysregulation of Endoplasmic Reticulum Stress and Autophagic Responses by the
      Antiretroviral Drug Efavirenz.
AB  - Increasing evidence demonstrates that the antiretroviral drugs (ARVds) used for
      human immunodeficiency virus (HIV) treatment have toxic effects that result in
      various cellular and tissue pathologies; however, their impact on the cells
      composing the blood-brain barrier is poorly understood. The current study focused
      on ARVds, used either in combination or alone, on the induction of endoplasmic
      reticulum (ER) stress responses in human brain endothelial cells. Among studied
      drugs (efavirenz, tenofovir, emtricitabine, lamivudine, and indinavir), only
      efavirenz increased ER stress via upregulation and activation of protein kinase
      like ER kinase PERK and inositol requiring kinase 1alpha (IRE1alpha). At the same
      time, efavirenz diminished autophagic activity, a surprising result because
      typically the induction of ER stress is linked to enhanced autophagy. These
      results were confirmed in microvessels of HIV transgenic mice chronically
      administered with efavirenz. In a series of further experiments, we identified
      that efavirenz dysregulated ER stress and autophagy by blocking the activity of
      the Beclin-1/Atg14/PI3KIII complex in regard to synthesis of phosphatidylinositol
      3-phosphate, a process that is linked to the formation of autophagosomes. Because
      autophagy is a protective mechanism involved in the removal of dysfunctional
      proteins and organelles, its inhibition can contribute to the toxicity of
      efavirenz or the development of neurodegenerative disease in HIV patients treated
      with this drug. 

PMID- 25987491
TI  - Heated jackets and dryland-based activation exercises used as additional warm-ups
      during transition enhance sprint swimming performance.
AB  - OBJECTIVES: The lengthy competition transition phases commonly experienced by
      competitive swimmers may mitigate the benefits of the pool warm-up. To combat
      this, we examined the impact of additional passive and active warm-up strategies
      on sprint swimming performance. DESIGN: Counterbalanced, repeated-measures cross
      over study. METHODS: Sixteen junior competitive swimmers completed a standardised
      pool warm-up followed by a 30min transition and 100m freestyle time-trial.
      Swimmers completed four different warm-up strategies during transition: remained
      seated wearing a conventional tracksuit top and pants (Control), wore an
      insulated top with integrated heating elements (Passive), performed a 5min
      dryland-based exercise circuit (Dryland), or a combination of Passive and Dryland
      (Combo). Swimming time-trial performance, core and skin temperature and
      perceptual variables were monitored. Time variables were normalised relative to
      Control. RESULTS: Both Combo (-1.05+/-0.26%; mean+/-90% confidence limits,
      p=0.00) and Dryland (-0.68+/-0.34%; p=0.02) yielded faster overall time-trial
      performances, with start times also faster for Combo (-0.37+/-0.07%; p=0.00)
      compared to Control. Core temperature declined less during transition with Combo
      (-0.13+/-0.25 degrees C; p=0.01) and possibly with Dryland (-0.24+/-0.13 degrees
      C; p=0.09) compared to Control (-0.64+/-0.16 degrees C), with a smaller reduction
      in core temperature related to better time-trial performance (R(2)=0.91; p=0.04).
      CONCLUSIONS: Dryland-based exercise circuits completed alone and in combination
      with the application of heated tracksuit jackets during transition can
      significantly improve sprint swimming performance. Attenuation in the decline of
      core temperature and a reduction in start time appear as likely mechanisms.

PMID- 25987492
TI  - Trunk muscle activation, fatigue and low back pain in tennis players.
AB  - OBJECTIVES: To analyze differences in trunk endurance time, fatigue and
      activation in tennis players with and without low back pain. DESIGN:
      Observational study, cross-sectional design. METHODS: Thirty-five tennis players
      completed an isometric trunk endurance protocol comprising four tasks (flexor,
      extensor and side bridge tests). LBP history was obtained through the Nordic
      Musculoskeletal Questionnaire. Endurance time was recorded for each test. Surface
      electromyographic activity was recorded bilaterally from rectus abdominis,
      external obliques, iliocostalis lumborum and longissimus thoracis. Average
      electromyographic amplitude and median frequency slopes during the tests were
      calculated and used as indicators of change in muscle activation and fatigue.
      RESULTS: Asymptomatic players had greater flexor (p=0.004) and right side bridge
      (p=0.043) endurance times. These players produced a greater increase in avrEMG
      during the right side bridge test for the left ES-I (p=0.046) and right EO
      (p=0.008). Players with LBP in the last 7 days showed reduced activation of the
      left (p=0.014) and right (p=0.013) ES-I and left longissimus thoracis (ES-L,
      p=0.047) in the extensor test. In the left side bridge test there was a lower
      avrEMG slope of the left EO (p=0.024) and left RA MF slope (p=0.011). In the
      right side bridge test a lower left ES-I avrEMG slope was found (p=0.048).
      CONCLUSIONS: Symptomatic players show lower activation of extensor muscles, less
      co-contraction patterns and less abdominal endurance. Tennis coaches and
      clinicians should consider these factors in their approach to players with LBP.

PMID- 25987493
TI  - Improving scientific production in cardiovascular rehabilitation: A reasonable
      challenge for the Annals?

PMID- 25987494
TI  - Ureteroenteric Strictures After Open Radical Cystectomy and Urinary Diversion:
      The University of Southern California Experience.
AB  - OBJECTIVE: To evaluate the risk factors, management, and outcomes of benign
      ureteroenteric strictures (UES) in patients undergoing open radical cystectomy
      (RC) and urinary diversion for urothelial bladder carcinoma. MATERIALS AND
      METHODS: Using our institutional review board-approved institutional bladder
      cancer database, we identified 1964 patients who underwent RC for urothelial
      bladder carcinoma between 1971 and 2008. Patients underwent a uniform refluxing
      ureteroenteric anastomosis technique to ileum. In patients with UES, we reviewed
      clinicopathologic, management, and outcome variables. A multivariate logistic
      regression model was used to identify independent UES predictors. RESULTS: Forty
      nine patients and 51 renal units were retrospectively identified with benign UES
      (2.6%). Median follow-up was 12.4 years (0.2-27.3 years) and median time from RC
      to UES diagnosis was 10 months (2 months-10 years). Although one-third were
      asymptomatic, common presentations included flank pain (22%) and urinary tract
      infection (9%). Thirty-one patients underwent primary endoscopic treatments,
      including dilatation and stenting, of whom, 13 patients (42%) underwent secondary
      endoscopic treatment and 9 patients (29%) underwent open revision. Three patients
      underwent primary open management. Median glomerular filtration rate did not
      change after management (49-48 mL/min); however, imaging showed improvement in
      50% of cases. A multivariate logistic regression model revealed no association
      with age, body mass index, Charlson comorbidity index, perioperative radiation or
      chemotherapy, or preoperative serum albumin in predicting UES. CONCLUSION: Benign
      UES are uncommon after RC and urinary diversion using a consistent meticulous
      surgical approach. More commonly on the left, UES generally present a few months
      after RC. Although no specific predisposing factor was determined, surgical
      technique plays an important role.

PMID- 25987495
TI  - Shut Phimosis in the Priapus Fresco From Pompeii.

PMID- 25987496
TI  - Rezum System Water Vapor Treatment for Lower Urinary Tract Symptoms/Benign
      Prostatic Hyperplasia: Validation of Convective Thermal Energy Transfer and
      Characterization With Magnetic Resonance Imaging and 3-Dimensional Renderings.
AB  - OBJECTIVE: To evaluate by magnetic resonance imaging the physical effects of
      convective thermal energy transfer with water vapor as a means of treating lower
      urinary tract symptoms due to benign prostatic hyperplasia. METHODS: Sixty-five
      men with lower urinary tract symptoms were treated with the Rezum System by
      transurethral intraprostatic injection of water vapor. A group of 45 of these men
      consented to undergo a series of gadolinium-enhanced magnetic resonance imagings
      of the prostate after treatment to monitor the size and location of ablative
      lesions, their time course of resolution, and the corresponding change in
      prostate tissue volume. Visualization was conducted at 1 week, 1, 3, and 6 months
      after treatment. RESULTS: Outcomes were available for 44 patients. Convective
      thermal lesions were limited to the transition zone and correlated with targeted
      treatment locations. At 1 week after treatment, the mean volume of ablative
      lesions was 8.2 cm(3) (0.5-24.0 cm(3)). At 6 months, whole prostate volume was
      reduced by a mean of 28.9% and transition zone volume by 38.0% as compared with
      baseline 1-week images. At 3 and 6 months after treatment, the lesion volumes had
      reduced by 91.5% and 95.1%, respectively. Lesions remained within the targeted
      treatment zone without compromising integrity of the bladder, rectum, or striated
      urinary sphincter. CONCLUSION: This imaging study confirms the delivery of
      convective water vapor technology to create thermal lesions in the prostate
      tissue. Lesions generated underwent near complete resolution by 3 and 6 months
      after treatment with a concomitant one-third reduction in overall prostate and
      transition zone volumes.

PMID- 25987497
TI  - Reconstruction after proximal gastrectomy for gastric cancer in the upper third
      of the stomach: a review of the literature published from 2000 to 2014.
AB  - Proximal gastrectomy (PG) is occasionally performed to preserve the physiological
      function of the remnant stomach with the aim of maintaining a gastric reservoir
      for patients with early gastric cancer in the upper third of the stomach. Many
      reconstructive procedures after PG have been reported, including
      esophagogastrostomy (EG), jejunal interposition, jejunal pouch interposition, and
      double tract. However, no general agreement exists regarding the optimal
      reconstructive procedure. This article reviews the current reconstructive
      procedures available for PG. We examined the surgical outcomes, postoperative
      complications, endoscopic findings, and quality of life (QOL) according to the
      reconstructive procedures. We found no significant difference in anastomotic
      leakage and anastomotic stricture among the procedures. The frequency of reflux
      esophagitis was higher with simple EG compared with the other reconstructive
      procedures. Some additional procedures, such as fundoplication, the use of a
      narrow gastric conduit, and placement of a gastric tube in the lower mediastinum
      on EG, could decrease the frequency of reflux esophagitis and reflux symptoms.
      These additional procedures may improve the QOL; however, the previous studies
      were small and could not adequately compare the reconstructive procedures.
      Prospective randomized controlled trials that involve a longer trial period and
      more institutions are needed to clarify the optimal reconstructive procedures
      after PG. 

PMID- 25987498
TI  - Vascular smooth muscle cell differentiation to an osteogenic phenotype involves
      matrix metalloproteinase-2 modulation by homocysteine.
AB  - Arterial calcification is common in vascular diseases and involves conversion of
      vascular smooth muscle cells (VSMCs) to an osteoblast phenotype. Clinical studies
      suggest that the development of atherosclerosis can be promoted by homocysteine
      (HCY), but the mechanisms remain unclear. Here, we determined whether increases
      in HCY levels lead to an increase in VSMC calcification and differentiation, and
      examined the role of an extracellular matrix remodeler, matrix metalloproteinase
      2 (MMP-2). Rat VSMCs were exposed to calcification medium in the absence or
      presence of HCY (10, 100 or 200 MUmol/L) or an MMP-2 inhibitor (10(-6) or 10(-5)
      mol/L). MTT assays were performed to determine the cytotoxicity of the MMP-2
      inhibitor in calcification medium containing 200 MUmol/L HCY. Calcification was
      assessed by measurements of calcium deposition and alkaline phosphatase (ALP)
      activity as well as von Kossa staining. Expression of osteocalcin, bone
      morphogenetic protein (BMP)-2, and osteopontin, and MMP-2 was determined by
      immunoblotting. Calcification medium induced osteogenic differentiation of VSMCs.
      HCY promoted calcification, increased osteocalcin and BMP-2 expression, and
      decreased expression of osteopontin. MMP-2 expression was increased by HCY in a
      dose-dependent manner in VSMCs exposed to both control and calcification medium.
      The MMP-2 inhibitor decreased the calcium content and ALP activity, and
      attenuated the osteoblastic phenotype of VSMCs. Vascular calcification and
      osteogenic differentiation of VSMCs were positively regulated by HCY through
      increased/restored MMP-2 expression, increased expression of calcification
      proteins, and decreased anti-calcification protein levels. In summary, MMP-2
      inhibition may be a protective strategy against VSMC calcification.

PMID- 25987499
TI  - Pharmacokinetics of topically applied recombinant human keratinocyte growth
      factor-2 in alkali-burned and intact rabbit eye.
AB  - Keratinocyte growth factor-2 (KGF-2), an effective agent in the development of
      epithelial tissue and regeneration during corneal wound healing, is a potential
      therapeutic option to treat the corneal diseases with corneal epithelial defects.
      However the tissue distribution and pharmacokinetics of KGF-2 have not been
      explored yet in eye upon topical application. Using (125)I-labeled recombinant
      human KGF-2 ((125)I-rhKGF-2), tissue distribution of rhKGF-2 in alkali-burned and
      control rabbit eyes was studied. Our results revealed that (125)I-rhKGF-2 was
      distributed to all eye tissues examined. The highest radioactivity level was
      found in the cornea, followed by iris, sclera, ciliary body, lens, aqueous humor,
      vitreous body, and serum in a greatest to least order. The levels of (125)I-rhKGF
      2 were higher in corneas of alkali-burned eyes than those in control eyes though
      without statistical significance. Calculated pharmacokinetic parameters of t1/2,
      Cmax, and Tmax of rhKGF-2 in the rabbit corneas were 3.4 h, 135.2 ng/ml, and 0.5
      h, respectively. In iris, lens, aqueous humor, and tear, t1/2, Cmax, and Tmax
      values were 6.2, 6.5, 5.2, and 2.5 h; 23.2, 4.5, 24.1, and 29,498.9 ng/ml; and
      1.0, 0.5, 0.5, and 1.0 h, respectively. Predominant and rapid accumulation of
      rhKGF-2 in corneas suggests that therapeutic doses of rhKGF-2 could be delivered
      by topical application for treatment of corneal diseases. 

PMID- 25987500
TI  - Sensorineural hearing loss and ischemic injury: Development of animal models to
      assess vascular and oxidative effects.
AB  - Hearing loss may be genetic, associated with aging or exposure to noise or
      ototoxic substances. Its aetiology can be attributed to vascular injury, trauma,
      tumours, infections or autoimmune response. All these factors could be related to
      alterations in cochlear microcirculation resulting in hypoxia, which in turn may
      damage cochlear hair cells and neurons, leading to deafness. Hypoxia could
      underlie the aetiology of deafness, but very few data about it are presently
      available. The aim of this work is to develop animal models of hypoxia and
      ischemia suitable for study of cochlear vascular damage, characterizing them by
      electrophysiology and gene/protein expression analyses. The effects of hypoxia in
      infarction were mimicked in rat by partial permanent occlusion of the left
      coronary artery, and those of ischemia in thrombosis by complete temporary
      carotid occlusion. In our models both hypoxia and ischemia caused a small but
      significant hearing loss, localized at the cochlear apex. A slight induction of
      the coagulation cascade and of oxidative stress pathways was detected as cell
      survival mechanism, and cell damages were found on the cuticular plate of outer
      hair cells only after carotid ischemia. Based on these data, the two developed
      models appear suitable for in vivo studies of cochlear vascular damage. 

PMID- 25987501
TI  - Even in the era of congenital hypothyroidism screening mild and subclinical
      sensorineural hearing loss remains a relatively common complication of severe
      congenital hypothyroidism.
AB  - Only few studies have focused on neurosensory hearing function of patients with
      congenital hypothyroidism (CH) identified by CH screening programs and treated
      early and, therefore, this issue remains still controversial. The aim of this
      study was to ascertain whether an early and adequate replacement treatment may be
      able to prevent sensorineural hearing loss in 32 screened children with CH and no
      associated risk factors for neuro-otologic alterations. These patients were
      recruited according to highly selective criteria aiming to preliminarily exclude
      the negative interference of both treatment variables and other underlying risk
      factors. All the selected patients underwent, at a median age of 15.4 years, an
      audiologic investigation, which evidenced a mild and subclinical hearing loss in
      25% of them. The poorest hearing scores were recorded in the individuals with
      athyreosis and in those with absence of distal femur bony nucleus at CH
      diagnosis. The prevalence of hearing impairment was significantly higher in CH
      patients than in 32 age-matched control subjects with no CH (chi(2) = 6.3, p <
      0.025). In light of these findings, we concluded that: a) 25% of CH patients
      detected by CH screening may show, at a median age of 15.4 years, a mild and
      subclinical hearing impairment, despite early and adequate replacement treatment;
      b) the risk of hearing loss is higher in CH young patients than in age-matched
      control subjects without CH; c) the risk of hearing loss is closely associated
      with the severity of CH; d) this risk is particularly relevant in the children
      with pre-natal onset of hypothyroidism. 

PMID- 25987502
TI  - Effects of a dexamethasone-releasing implant on cochleae: A functional,
      morphological and pharmacokinetic study.
AB  - AIM: This study evaluated the impact of a dexamethasone-releasing silicone
      implant on hearing function preservation, cochlear morphology and perilymph
      pharmacokinetics after cochlear implantation. METHODS: Guinea pigs were implanted
      unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n
      = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response
      (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured
      preoperatively and over 6 months postoperatively. Cochlear histology using
      standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)
      alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were
      involved in the pharmacokinetic study, and real-time drug concentrations in
      perilymph were investigated using high-performance liquid chromatography (HPLC).
      The Mann-Whitney U test (1-tailed) was used for statistical analyses. RESULTS:
      ABR and DPOAE testing demonstrated decreased hearing function immediately
      postoperatively followed by a progressive hearing loss within the first day
      postoperatively. There was almost no observable hearing improvement in the
      control group from 1 week to 6 months postoperatively, but hearing levels in the
      DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA
      and control group was 5.0 +/- 3.4 dB and 21.7 +/- 5.3 dB, respectively at a 16
      kHz stimulus frequency 6 months postoperatively. The difference in threshold
      shifts was present throughout all measured frequencies, and it was significant at
      4-24 kHz. The morphological study revealed new fibrosis formation in the scala
      tympani, which encapsulated the implanted electrode. TNF-alpha positive staining
      in the cochleae of the DEXA group was less evident than the control group. The
      pharmacokinetic study revealed a peak perilymph concentration 30 min
      postoperatively and sustained dexamethasone release at least 1 week
      postoperatively. CONCLUSION: Cochlear implants that incorporate dexamethasone can
      release drug chronically in the inner ear and induce significant long-term
      recovery and preservation of auditory function after implantation.

PMID- 25987504
TI  - The application of genome editing in studying hearing loss.
AB  - Targeted genome editing mediated by clustered, regularly interspaced, short
      palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has
      emerged as one of the most powerful tools to study gene functions, and with
      potential to treat genetic disorders. Hearing loss is one of the most common
      sensory disorders, affecting approximately 1 in 500 newborns with no treatment.
      Mutations of inner ear genes contribute to the largest portion of genetic
      deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in
      human cells and model organisms such as zebrafish, mice and primates make it a
      promising technology in hearing research. With CRISPR/Cas9 technology, functions
      of inner ear genes can be studied efficiently by the disruption of normal gene
      alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing
      loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed
      repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore
      hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be
      efficiently performed in the mammalian inner ear in vivo. Thus, application of
      CRISPR/Cas9 in hearing research will open up new avenues for understanding the
      pathology of genetic hearing loss and provide new routes in the development of
      treatment to restore hearing. In this review, we describe major methodologies
      currently used for genome editing. We will highlight applications of these
      technologies in studies of genetic disorders and discuss issues pertaining to
      applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing
      loss. 

PMID- 25987505
TI  - Endolymphatic hydrops is prevalent in the first weeks following cochlear
      implantation.
AB  - AIM: To explore morphological or electrophysiological evidence for the presence
      of endolymphatic hydrops (EH) in guinea pig cochleae in the first 3 months after
      cochlear implantation. METHODS: Dummy silastic electrodes were implanted
      atraumatically into the basal turn of scala tympani via a cochleostomy. Round
      window electrocochleography (ECochG) was undertaken prior to and after
      implantation. Animals survived for 1, 7, 28 or 72 days prior to a terminal
      experiment, when ECochG was repeated. The cochleae were imaged using micro-CT
      after post-fixing with osmium tetroxide to reveal the inner ear soft tissue
      structure. EH was assessed by visual inspection at a series of frequency specific
      places along the length of the cochlea, and the extent to which Reissner's
      membrane departed from its neutral position was quantified. Tissue response
      volumes were calculated. Using ECochG, the ratio of the summating potential to
      the action potential (SP/AP ratio) was calculated in response to frequencies
      between 2 and 32 kHz. RESULTS: There was minimal evidence of electrode trauma
      from cochlear implantation on micro-CT imaging. Tissue response volumes did not
      change over time. EH was most prevalent 7 days after surgery in implanted ears,
      as determined by visual inspection. Scala media areas were increased, as expected
      in cases of EH, over the first month after cochlear implantation. SP/AP ratios
      decreased immediately after surgery, but were elevated 1 and 7 days after
      implantation. CONCLUSIONS: EH is prevalent in the first weeks after implant
      surgery, even in the absence of significant electrode insertion trauma.

PMID- 25987503
TI  - Biology and pathobiology of lipid droplets and their potential role in the
      protection of the organ of Corti.
AB  - The current review article seeks to extend our understanding on the role of lipid
      droplets within the organ of Corti. In addition to presenting an overview of the
      current information about the origin, structure and function of lipid droplets we
      draw inferences from the collective body of knowledge about this cellular
      organelle to build a conceptual framework to better understanding their role in
      auditory function. This conceptual model considers that lipid droplets play a
      significant role in the synthesis, storage, and release of lipids and proteins
      for energetic use and/or modulating cell signaling pathways. We describe the role
      and mechanism by which LD play a role in human diseases, and we also review
      emerging data from our laboratory revealing the potential role of lipid droplets
      from Hensen cells in the auditory organ. We suggest that lipid droplets might
      help to develop rapidly and efficiently the resolution phase of inflammatory
      responses in the mammalian cochlea, preventing inflammatory damage of the
      delicate inner ear structures and, consequently, sensorineural hearing loss.

PMID- 25987506
TI  - Intestinal intraepithelial lymphocyte activation promotes innate antiviral
      resistance.
AB  - Unrelenting environmental challenges to the gut epithelium place particular
      demands on the local immune system. In this context, intestinal intraepithelial
      lymphocytes (IEL) compose a large, highly conserved T cell compartment,
      hypothesized to provide a first line of defence via cytolysis of dysregulated
      intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC.
      Here we show that one of the most conspicuous impacts of activated IEL on IEC is
      the functional upregulation of antiviral interferon (IFN)-responsive genes,
      mediated by the collective actions of IFNs with other cytokines. Indeed, IEL
      activation in vivo rapidly provoked type I/III IFN receptor-dependent
      upregulation of IFN-responsive genes in the villus epithelium. Consistent with
      this, activated IEL mediators protected cells against virus infection in vitro,
      and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence,
      intraepithelial T cell activation offers an overt means to promote the innate
      antiviral potential of the intestinal epithelium. 

PMID- 25987508
TI  - Identifying and cultivating superforecasters as a method of improving
      probabilistic predictions.
AB  - Across a wide range of tasks, research has shown that people make poor
      probabilistic predictions of future events. Recently, the U.S. Intelligence
      Community sponsored a series of forecasting tournaments designed to explore the
      best strategies for generating accurate subjective probability estimates of
      geopolitical events. In this article, we describe the winning strategy: culling
      off top performers each year and assigning them into elite teams of
      superforecasters. Defying expectations of regression toward the mean 2 years in a
      row, superforecasters maintained high accuracy across hundreds of questions and a
      wide array of topics. We find support for four mutually reinforcing explanations
      of superforecaster performance: (a) cognitive abilities and styles, (b) task
      specific skills, (c) motivation and commitment, and (d) enriched environments.
      These findings suggest that superforecasters are partly discovered and partly
      created-and that the high-performance incentives of tournaments highlight aspects
      of human judgment that would not come to light in laboratory paradigms focused on
      typical performance. 

PMID- 25987507
TI  - Heritability, SNP- and Gene-Based Analyses of Cannabis Use Initiation and Age at
      Onset.
AB  - Prior searches for genetic variants (GVs) implicated in initiation of cannabis
      use have been limited to common single nucleotide polymorphisms (SNPs) typed in
      HapMap samples. Denser SNPs are now available with the completion of the 1000
      Genomes and the Genome of the Netherlands projects. More densely distributed SNPs
      are expected to track the causal variants better. Therefore we extend the search
      for variants implicated in early stages of cannabis use to previously untagged
      common and low-frequency variants. We run heritability, SNP and gene-based
      analyses of initiation and age at onset. This is the first genome-wide study of
      age at onset to date. Using GCTA and a sample of distantly related individuals
      from the Netherlands Twin Register, we estimated that the currently measured (and
      tagged) SNPs collectively explain 25 % of the variance in initiation (SE = 0.088;
      P = 0.0016). Chromosomes 4 and 18, previously linked with cannabis use and other
      addiction phenotypes, account for the largest amount of variance in initiation
      (6.8 %, SE = 0.025, P = 0.002 and 3.6 %, SE = 0.01, P = 0.012, respectively). No
      individual SNP- or gene-based test reached genomewide significance in the
      initiation or age at onset analyses. Our study detected association signal in the
      currently measured SNPs. A comparison with prior SNP-heritability estimates
      suggests that at least part of the signal is likely coming from previously
      untyped common and low frequency variants. Our results do not rule out the
      contribution of rare variants of larger effect-a plausible source of the
      difference between the twin-based heritability estimate and that from GCTA. The
      causal variants are likely of very small effect (i.e., <1 % explained variance)
      and are uniformly distributed over the genome in proportion to chromosomes'
      length. Similar to other complex traits and diseases, detecting such small
      effects is to be expected in sufficiently large samples.

PMID- 25987509
TI  - One Century of Global IQ Gains: A Formal Meta-Analysis of the Flynn Effect (1909
      2013).
AB  - The Flynn effect (rising intelligence test performance in the general population
      over time and generations) varies enigmatically across countries and intelligence
      domains; its substantive meaning and causes remain elusive. This first formal
      meta-analysis on the topic revealed worldwide IQ gains across more than one
      century (1909-2013), based on 271 independent samples, totaling almost 4 million
      participants, from 31 countries. Key findings include that IQ gains vary
      according to domain (estimated 0.41, 0.30, 0.28, and 0.21 IQ points annually for
      fluid, spatial, full-scale, and crystallized IQ test performance, respectively),
      are stronger for adults than children, and have decreased in more recent decades.
      Altogether, these findings narrow down proposed theories and candidate factors
      presumably accounting for the Flynn effect. Factors associated with life history
      speed seem mainly responsible for the Flynn effect's general trajectory, whereas
      favorable social multiplier effects and effects related to economic prosperity
      appear to be responsible for observed differences of the Flynn effect across
      intelligence domains. 

PMID- 25987510
TI  - How can intergroup interaction be bad if intergroup contact is good? Exploring
      and reconciling an apparent paradox in the science of intergroup relations.
AB  - The outcomes of social interactions among members of different groups (e.g.,
      racial groups, political groups, sexual orientation groups) have long been of
      interest to psychologists. Two related literatures on the topic have emerged-the
      intergroup interaction literature and the intergroup contact literature-in which
      divergent conclusions have been reported. Intergroup interaction is typically
      found to have negative effects tied to intergroup bias, producing heightened
      stress, intergroup anxiety, or outgroup avoidance, whereas intergroup contact is
      typically found to have positive effects tied to intergroup bias, predicting
      lower intergroup anxiety and lower prejudice. We examine these paradoxical
      findings, proposing that researchers contributing to the two literatures are
      examining different levels of the same phenomenon and that methodological
      differences can account for the divide between the literatures. Further, we
      introduce a mathematical model by which the findings of the two literatures can
      be reconciled. We believe that adopting this model will streamline thinking in
      the field and will generate integrative new research in which investigators
      examine how a person's experiences with diversity unfold. 

PMID- 25987512
TI  - The psychology of home environments: a call for research on residential space.
AB  - Homes are important: People devote much of their thought, time, and resources to
      selecting, modifying, and decorating their living spaces, and they may be
      devastated when their homes must be sold or are destroyed. Yet the empirical
      psychological literature says virtually nothing about the roles that homes might
      play in people's lives. We argue that homes provide an informative context for a
      wide variety of studies examining how social, developmental, cognitive, and other
      psychological processes play out in a consequential real-world setting. The topic
      of homes is also well suited to collaborations with a diverse array of
      disciplines ranging from architecture and engineering to sociology and law. We
      illustrate the potential insights to be gained from studying homes with an
      exploratory study that maps the psychological ambiances (e.g., romance, comfort,
      togetherness) that people desire in their homes; we identify six broad ambiance
      dimensions (restoration, kinship, storage, stimulation, intimacy, productivity)
      that show mean differences across rooms. We connect these findings to existing
      work on situation selection in emotion regulation. These ideas provide only an
      initial foray into the domain of residential space, but they hint at the
      productive roles that homes and other spaces could play in psychological
      theorizing and research. 

PMID- 25987514
TI  - Introduction to the special section on methods: odds and end.

PMID- 25987511
TI  - Affective science perspectives on cancer control: strategically crafting a
      mutually beneficial research agenda.
AB  - Cancer control research involves the conduct of basic and applied behavioral and
      social sciences to reduce cancer incidence, morbidity, and mortality and improve
      quality of life. Given the importance of behavior in cancer control, fundamental
      research is necessary to identify psychological mechanisms underlying cancer
      risk, prevention, and management behaviors. Cancer prevention, diagnosis, and
      treatment are often emotionally laden. As such, affective science research to
      elucidate questions related to the basic phenomenological nature of emotion,
      stress, and mood is necessary to understand how cancer control can be hindered or
      facilitated by emotional experiences. To date, the intersection of basic
      affective science research and cancer control remains largely unexplored. The
      goal of this article is to outline key questions in the cancer control research
      domain that provide an ecologically valid context for new affective science
      discoveries. We also provide examples of ways in which basic affective
      discoveries could inform future cancer prevention and control research. These
      examples are not meant to be exhaustive or prescriptive but instead are offered
      to generate creative thought about the promise of a cancer research context for
      answering basic affective science questions. Together, these examples provide a
      compelling argument for fostering collaborations between affective and cancer
      control scientists. 

PMID- 25987515
TI  - Scientific disintegrity as a public bad.
AB  - In this article, I argue that scientific dishonesty essentially results from an
      incentive problem; I do so using a standard economic model-the public bad.
      Arguably, at least in the short run, most scientists would increase their
      personal utility by being sloppy with scientific standards. Yet, if they do, it
      becomes more difficult for all scientists to make their voice heard in society,
      to convince policy makers to assign public funds to academia, and to lead
      fulfilling academic lives. The nature of the ensuing governance problem (and
      appropriate policy intervention) hinges on the definition of scientists' utility
      function. The policy problem is less grave if society attaches disproportionally
      more weight to severe or widespread violations and if individual scientists do
      not precisely know in advance when they will quit their academic lives. If most
      scientists internalize most scientific standards, then the problem is alleviated.
      However, internalization is immaterial if honorable scientists dislike that
      others advance their careers by violating those standards. Sanctions are helpful,
      even if relatively mild. However, it is important to also punish those who do not
      punish others for breaking the rules or, alternatively, to put some centralized
      mechanism for vigilance and enforcement into place. 

PMID- 25987516
TI  - Many replications do not causal inferences make: the need for critical
      replications to test competing explanations of nonrandomized studies.
AB  - Although direct replications are ideal for randomized studies, areas of
      psychological science that lack randomized studies should incorporate Rosenbaum's
      (2001) distinction between trivial and nontrivial replications, relabeled herein
      as exact and critical replications. If exact replications merely repeat
      systematic biases, they cannot enhance cumulative progress in psychological
      science. In contrast, critical replications distinguish between competing
      explanations by using crucial tests to clarify the underlying causal influences.
      We illustrate this potential with examples from research on corrective actions by
      professionals (e.g., psychotherapy, Ritalin) and parents (e.g., spanking,
      homework assistance), where critical replications are needed to overcome the
      inherent selection bias due to corrective actions being triggered by children's
      symptoms. Purported causal effects must first prove to be replicable after
      plausible confounds such as selection bias are eliminated. Subsequent critical
      replications can then compare plausible alternative explanations of the average
      unbiased causal effect and of individual differences in those effects. We
      conclude that this type of systematic sequencing of critical replications has
      more potential for making the kinds of discriminations typical of cumulative
      progress in science than do exact replications alone, especially in areas where
      randomized studies are unavailable. 

PMID- 25987517
TI  - Replicating studies in which samples of participants respond to samples of
      stimuli.
AB  - In a direct replication, the typical goal is to reproduce a prior experimental
      result with a new but comparable sample of participants in a high-powered
      replication study. Often in psychology, the research to be replicated involves a
      sample of participants responding to a sample of stimuli. In replicating such
      studies, we argue that the same criteria should be used in sampling stimuli as
      are used in sampling participants. Namely, a new but comparable sample of stimuli
      should be used to ensure that the original results are not due to idiosyncrasies
      of the original stimulus sample, and the stimulus sample must often be enlarged
      to ensure high statistical power. In support of the latter point, we discuss the
      fact that in experiments involving samples of stimuli, statistical power
      typically does not approach 1 as the number of participants goes to infinity. As
      an example of the importance of sampling new stimuli, we discuss the bygone
      literature on the risky shift phenomenon, which was almost entirely based on a
      single stimulus sample that was later discovered to be highly unrepresentative.
      We discuss the use of both resampled and expanded stimulus sets, that is,
      stimulus samples that include the original stimuli plus new stimuli. 

PMID- 25987518
TI  - On the applied implications of the "verbal overshadowing effect".
AB  - Schooler and Engstler-Schooler (1990) found that participants who wrote out a
      description of the perpetrator's face after watching a simulated crime video were
      subsequently less likely to identify that perpetrator from a photo lineup
      compared to participants in a control condition (i.e., the correct ID rate was
      reduced). The first registered replication report in Perspectives on
      Psychological Science confirmed this verbal overshadowing effect (Alogna et al.,
      2014). Does this result indicate a reduced ability to recognize the person who
      was verbally described, or does it instead reflect more conservative responding?
      The answer depends on the still unknown likelihood of identifying an innocent
      suspect from a lineup (the false ID rate). Assuming the reduced correct ID rate
      does reflect memory impairment, should the legal system be advised to give less
      weight to a suspect identification if the witness previously provided a verbal
      description of the perpetrator? Intuitively, the answer is "yes," but without
      knowing the false ID rate, it is unclear if a suspect identification following a
      verbal description should be given less weight or more weight. This is true even
      if the correct and false ID rates show that verbal descriptions impair memory. In
      our view, psychologists should withhold giving advice to the legal system about
      the effect of verbal descriptions on suspect identifications until the issue is
      investigated by including lineups that contain an innocent suspect. 

PMID- 25987519
TI  - On Klatzky and Creswell (2014): saving social priming effects but losing science
      as we know it?
AB  - Klatzky and Creswell (2014) offer an interpretation of the unreliability of
      social priming effects by analogizing them to what is known about the complexity
      of cross-modal transfer effects in perception. The complexity of these transfer
      effects arises because they are both multiply determined and stochastic. In this
      commentary, I argue that Klatzky and Creswell's thoughtful contribution raises
      the possibility that there might be deep and substantive limits to both the
      replicability and the generalizability of many of the phenomena that most
      interest psychologists, including social priming effects. Psychological phenomena
      largely governed by what Fodor (1983) called the "central system" may resist both
      replication and generalization by their very nature and not because of weak and
      underpowered experimental methods. With such phenomena, science might give us
      very good tools for explanation, but not for prediction (replication).

PMID- 25987520
TI  - Theory building, replication, and behavioral priming: where do we need to go from
      here?
AB  - This article suggests that the field of behavioral priming, which is basically a
      technique, is in need of theory building. Guidelines from successful theory
      building by induction in the realm of conscious motivation (namely, goal setting
      and self-efficacy) are suggested. The process would include replication with
      variation, identifying the logical relation between a given prime and the action
      in question, discovering moderators and mediators, and clarifying the
      relationship between the conscious mind and the subconscious. 

PMID- 25987522
TI  - Complications of Electromechanical Morcellation Reported in the Manufacturer and
      User Facility Device Experience (MAUDE) Database.
AB  - STUDY OBJECTIVE: To evaluate adverse events associated with electromechanical
      morcellation as reported to the Manufacturer and User Facility Device Experience
      (MAUDE) database. DESIGN: Retrospective analysis of an established database
      (Canadian Task Force classification III). INTERVENTION: A search of the MAUDE
      database for terms associated with commercially available electromechanical
      morcellation devices was undertaken for events leading to injury or death between
      2004 and 2014. Data, including the types of injury, need for conversion to open
      surgery, type of open surgery, and clinical outcomes, were extracted from the
      records. MEASUREMENTS AND MAIN RESULTS: Over a 10-year period, 9 events
      associated with death and 215 events associated with patient injury or
      significant delay of the surgical procedure were recorded. These involved 137
      device failures, 51 organ injuries, and the morcellation of 27 previously
      undiagnosed malignancies. Of the 9 deaths, 1 was associated with organ injury,
      and the other 8 were associated with morcellation of cancer. Of the 27
      undiagnosed cancers, 5 were reported by the manufacturer, 8 were reported by the
      patient or family, 9 were reported by medical or news reports, 2 were reported by
      medical professionals, and 3 were due to litigation. Morcellation of an
      undiagnosed malignancy was first reported to the database in December 2013.
      CONCLUSIONS: The MAUDE database appears to detect perioperative events, such as
      device failures and organ injury at the time of surgery, but appears to be poor
      at detecting late events after surgery, such as the potential spread of cancer.
      Outcome registries are likely a more efficient means of tracking potential long
      term adverse events associated with surgical devices.

PMID- 25987523
TI  - Telelap Alf-X-Assisted Laparoscopy for Ovarian Cyst Enucleation: Report of the
      First 10 Cases.
AB  - This prospective single-institutional clinical trial sought to assess the safety
      and feasibility of laparoscopic benign ovarian cyst enucleation with a novel
      robotic-assisted laparoscopic system. Here we report a series of 10 patients
      treated using the Telelap ALF-X system in the first clinical application on
      patients at the Division of Gynecologic Oncology, Catholic University of the
      Sacred Heart of Rome. The primary inclusion criterion was the presence of
      monolateral ovarian cyst without a preoperative assessment suspicious for
      malignancy. Intraoperative data, including docking time, operative time,
      estimated blood loss, intraoperative and perioperative complications, and
      conversion to either standard laparoscopy or laparotomy, were collected. The
      cysts were removed with an ovary-sparing technique with respect to conservative
      surgical principles. The median operative time was 46.3 minutes, and patients
      without postoperative complications were discharged at 1 or 2 days after the
      procedure. Telelap ALF-X laparoscopic enucleation of benign ovarian cysts with an
      ovary-sparing technique is feasible, safe, and effective; however, more clinical
      data are needed to determine whether this approach can offer any other benefits
      over other minimally invasive surgical techniques. 

PMID- 25987524
TI  - Postcoital Bleeding From a Vaginal Lesion.

PMID- 25987525
TI  - Facile construction of dual-bioresponsive biodegradable micelles with superior
      extracellular stability and activated intracellular drug release.
AB  - It is still a major challenge for targeted cancer chemotherapy to design stable
      biodegradable micellar drug delivery systems which show a rapid and complete
      intracellular drug release. Here, reversibly core-crosslinked pH-responsive
      biodegradable micelles were developed based on poly(ethylene glycol)-poly(2,4,6
      trimethoxybenzylidene-pentaerythritol carbonate-co-pyridyl disulfide carbonate)
      [PEG-P(TMBPEC-co-PDSC)] copolymers and investigated for intracellular doxorubicin
      (DOX) release. PEG-P(TMBPEC-co-PDSC) copolymers formed micelles with a small size
      of 58.6nm were readily crosslinked by the addition of dithiothreitol (DTT).
      Notably, in vitro release studies showed that under physiological conditions only
      ca. 19.9% of DOX was released from the reversibly crosslinked micelles in 24h at
      a low micelle concentration of 40MUg/mL. The release of DOX was accelerated at
      pH5.0 or in the presence of 10mM glutathione (GSH) at pH7.4, in which 64.2% and
      44.1% of DOX was released, respectively, in 24h. The drug release was further
      boosted at pH5.0 and 10mM GSH, with 98.8% of DOX released in 12h. Moreover, DOX
      release was also facilitated by a 4h incubation at pH5.0 followed by incubation
      at pH7.4 with 10mM GSH. Confocal microscopy indicated that DOX was delivered and
      released into the nuclei of RAW 264.7 cells following a 12h incubation with DOX
      loaded reversibly crosslinked micelles. MTT assays revealed that DOX-loaded
      reversibly crosslinked micelles had much higher antitumor activity than
      irreversibly crosslinked controls, with low IC50 values of 1.65 and 1.14MUg/mL
      for HeLa and RAW 264.7 cells, respectively, following a 48h incubation. The blank
      crosslinked micelles had a low cytotoxicity of up to a concentration of 0.8mg/mL.
      These reversibly crosslinked pH-sensitive biodegradable micelles with superior
      extracellular stability but activated intracellular drug release provide a novel
      platform for tumor-targeting drug delivery. 

PMID- 25987526
TI  - Achieving an ultra-narrow multiband light absorption meta-surface via coupling
      with an optical cavity.
AB  - Resonant plasmonic and metamaterial absorbers are of particular interest for
      applications in a wide variety of nanotechnologies including thermophotovoltaics,
      photothermal therapy, hot-electron collection and biosensing. However, it is
      rather challenging to realize ultra-narrow absorbers using plasmonic materials
      due to large optical losses in metals that inevitably decrease the quality of
      optical resonators. Here, we theoretically report methods to achieve an ultra
      narrow light absorption meta-surface by using photonic modes of the optical
      cavities, which strongly couple with the plasmon resonances of the metallic
      nanostructures. Multispectral light absorption with absorption amplitude
      exceeding 99% and a bandwidth approaching 10 nm is achieved at the optical
      frequencies. Moreover, by introducing a thick dielectric coupling cavity, the
      number of absorption bands can be strongly increased and the bandwidth can even
      be narrowed to less than 5 nm due to the resonant spectrum splitting enabled by
      strong coupling between the plasmon resonances and the optical cavity modes.
      Designing such optical cavity-coupled meta-surface structures is a promising
      route for achieving ultra-narrow multiband absorbers, which can be used in
      absorption filters, narrow-band multispectral thermal emitters and
      thermophotovoltaics. 

PMID- 25987527
TI  - Systematics and biogeography of the Hylarana frog (Anura: Ranidae) radiation
      across tropical Australasia, Southeast Asia, and Africa.
AB  - We present an inclusive molecular phylogeny for Hylarana across its global
      distribution, utilizing two mitochondrial and four nuclear gene regions for 69 of
      the 97 currently described species. We use phylogenetic methods to test monophyly
      of Hylarana, determine relationships among ten putative subgenera, identify major
      clades, reconstruct biogeographic history, and estimate continental dispersal
      dates. Results support Hylarana as a monophyletic group originating approximately
      26.9MYA and comprising eight clades that partly correspond to currently described
      subgenera plus two new groups. The African and Australasian species each form
      clades embedded within a paraphyletic Southeast Asian group. We estimate that
      Africa and Australasia were colonized by Hylarana s.l. from SE Asia approximately
      18.7 and 10.8MYA, respectively. Biogeographic reconstructions also support three
      separate colonization events in India from Southeast Asia. Examination of museum
      specimens identified morphological characters useful for delineating subgenera
      and species. We herein elevate all supported subgenera to genus rank and formally
      describe two new genera to produce a revised taxonomy congruent with our new
      phylogenetic and biogeographic findings. 

PMID- 25987528
TI  - Fleas (Siphonaptera) are Cretaceous, and evolved with Theria.
AB  - Fleas (order Siphonaptera) are highly-specialized, diverse blood-feeding
      ectoparasites of mammals and birds with an enigmatic evolutionary history and
      obscure origin. We here present a molecular phylogenetic study based on a
      comprehensive taxon sampling of 259 flea taxa, representing 16 of the 18 extant
      families of this order. A Bayesian phylogenetic tree with strong nodal support
      was recovered, consisting of seven sequentially derived lineages with
      Macropsyllidae as the earliest divergence, followed by Stephanocircidae.
      Divergence times of flea lineages were estimated based on fossil records and host
      specific associations to bats (Chiroptera), suggesting that the common ancestor
      of extant Siphonaptera diversified during the Cretaceous. However, most of the
      intraordinal divergence into extant lineages took place after the K-Pg boundary.
      Ancestral states of host association and biogeographical distribution were
      reconstructed, suggesting with high likelihood that fleas originated in the
      southern continents (Gondwana) and migrated from South America to their extant
      distributions in a relatively short time frame. Theria (placental mammals and
      marsupials) represent the most likely ancestral host group of extant
      Siphonaptera, with marsupials occupying a more important role than previously
      assumed. Major extant flea families evolved in connection to post K-Pg
      diversification of Placentalia. The association of fleas with monotremes and
      birds is likely due to later secondary host association. These results suggest
      caution in casually interpreting recently discovered Mesozoic fossil "dinosaur
      fleas" of Northeast Asia as part of what we currently consider Siphonaptera. 

PMID- 25987529
TI  - Hidden relationships and genetic diversity: Molecular phylogeny and
      phylogeography of the Levantine lizards of the genus Phoenicolacerta (Squamata:
      Lacertidae).
AB  - The Levant region witnessed dramatic tectonic events and climatic fluctuations
      that changed the historical landscape of the area and consequently influenced the
      cladogenesis and distribution of the local biota. In this study we use
      information from two mitochondrial and two nuclear genes and species delimitation
      methods in order to obtain the first robust time-calibrated molecular phylogeny
      of the Levantine rock lizards of the genus Phoenicolacerta. We sampled from
      across its distributional range with the aim to clarify its systematics,
      biogeography and evolution. Our results suggest that the genus includes two well
      supported clades, one comprising solely the montane species Phoenicolacerta
      kulzeri, and the other including the three remaining species, the relatively
      widespread, P. laevis, the Syrian-Turkish P. cyanisparsa and the Cypriot endemic
      P. troodica. We found that both P. laevis and P. cyanisparsa are not
      monophyletic, as the Turkish populations of P. laevis branch within P.
      cyanisparsa. We found high levels of undescribed diversity within P. laevis which
      necessitate a thorough revision. We suggest that Phoenicolacerta started
      radiating during the mid-late Miocene, and that both vicariance and dispersal
      events shaped the diversification and distribution of the genus concomitantly
      with the formation of major geological structures and climatic fluctuations in
      the Levant. These results highlight the region as an important center of
      speciation, contributing to the species diversity of the eastern Mediterranean. 

PMID- 25987530
TI  - Scorpion speciation in the Holy Land: Multilocus phylogeography corroborates
      diagnostic differences in morphology and burrowing behavior among Scorpio
      subspecies and justifies recognition as phylogenetic, ecological and biological
      species.
AB  - Scorpio Linnaeus, 1758 (family Scorpionidae Latreille, 1802) was considered
      monotypic for over a century, and comprised a single species, Scorpio maurus
      Linnaeus, 1758, with 19 subspecies, distributed from West Africa, throughout the
      Maghreb and the Middle East, to Iran. Two parapatric subspecies, Scorpio maurus
      fuscus (Ehrenberg, 1829) and Scorpio maurus palmatus (Ehrenberg, 1828), have long
      been recognized in the eastern Mediterranean region. We examined morphological
      variation, burrow architecture and genetic divergence among 39 populations across
      the distribution of the two subspecies to assess whether they are conspecific
      and, if not, how many species might be involved. Cuticle coloration, pedipalp
      chela digital carina condition, and selected measurements were recorded. Sixty
      burrows were excavated and examined for burrow structure and depth. A multilocus
      dataset comprising concatenated fragments of one nuclear (28S rDNA) and three
      mitochondrial (12S rDNA, 16S rDNA, Cytochrome c Oxidase Subunit I) loci, totaling
      ca. 2400 base-pairs, was produced for 41 individuals, and a single-locus dataset
      comprising 658 base-pairs of the COI locus for 156 individuals. Despite
      overlapping ranges in morphometric characters of pedipalp chela shape, the
      putative subspecies were easily distinguished by cuticle coloration and condition
      of the pedipalp chela digital carina, and were also found to differ significantly
      in burrow architecture and depth. Phylogeographical analyses of the COI and
      multilocus datasets recovered seven distinct clades. Separate analyses of
      mitochondrial sequences, and combined analyses of mitochondrial and nuclear
      sequences support most clades. The two major clades corresponded with the
      geographical distributions of S. m. fuscus and S. m. palmatus in the region.
      Specimens from these clades were genetically distinct, and exhibited different
      burrow structure in geographically-proximate localities, suggesting reproductive
      isolation. The palmatus clade included two distinct subclades of specimens from
      localities adjacent to the Dead Sea. Three other clades, comprising specimens
      from the most northeastern localities, were tentatively assigned to subspecies
      previously recorded in neighboring Jordan and Syria. The morphological,
      behavioral and genetic evidence supports previous suggestions that Scorpio maurus
      is a species complex and justifies the following taxonomic emendations: Scorpio
      fuscus (Ehrenberg, 1829), stat. nov.; Scorpio kruglovi Birula, 1910, stat. nov.;
      Scorpio palmatus (Ehrenberg, 1828), stat. nov.; Scorpio propinquus (Simon, 1872),
      stat. nov. 

PMID- 25987531
TI  - Comparative phylogeography of co-distributed Phrygilus species (Aves, Thraupidae)
      from the Central Andes.
AB  - The Neotropical ecoregion has been an important place of avian diversification
      where dispersal and allopatric events coupled with periods of active orogeny and
      climate change (Late Pliocene-Pleistocene) have shaped the biogeography of the
      region. In the Neotropics, avian population structure has been sculpted not only
      by geographical barriers, but also by non-allopatric factors such as natural
      selection and local adaptation. We analyzed the genetic variation of six co
      distributed Phrygilus species from the Central Andes, based on mitochondrial and
      nuclear markers in conjunction with morphological differentiation. We examined if
      Phrygilus species share patterns of population structure and historical
      demography, and reviewed the intraspecific taxonomy in part of their geographic
      range. Our results showed different phylogeographic patterns between species,
      even among those belonging to the same phylogenetic clade. P. alaudinus, P.
      atriceps, and P. unicolor showed genetic differentiation mediated by allopatric
      mechanisms in response to specific geographic barriers; P. gayi showed sympatric
      lineages in northern Chile, while P. plebejus and P. fruticeti showed a single
      genetic group. We found no relationship between geographic range size and genetic
      structure. Additionally, a signature of expansion was found in three species
      related to the expansion of paleolakes in the Altiplano region and the drying
      phase of the Atacama Desert. Morphological analysis showed congruence with
      molecular data and intraspecific taxonomy in most species. While we detected
      genetic and phenotypic patterns that could be related to natural selection and
      local adaptation, our results indicate that allopatric events acted as a major
      factor in the population differentiation of Phrygilus species. 

PMID- 25987532
TI  - Who's getting around? Assessing species diversity and phylogeography in the
      widely distributed lichen-forming fungal genus Montanelia (Parmeliaceae,
      Ascomycota).
AB  - Brown parmelioid lichens comprise a number of distinct genera in one of the most
      species-rich families of lichen-forming fungi, Parmeliaceae (Ascomycota). In
      spite of their superficial similarity, a number of studies of brown parmelioids
      have provided important insight into diversification in lichen-forming fungi with
      cosmopolitan distributions. In this study we assess species diversity,
      biogeography and diversification of the genus Montanelia, which includes alpine
      to temperate saxicolous species. We sampled each of the five known species, four
      of which are known from broad, intercontinental distributions. In order to
      identify potential biogeographical patterns, each broadly distributed species was
      represented by individuals collected across their intercontinental distributions.
      Molecular sequence data were generated for six loci, including three nuclear
      protein-coding markers (MCM7, RPB1, and RPB2), two nuclear ribosomal markers (ITS
      and nrLSU), and a fragment of the mitochondrial small subunit. We used three
      sequence-based species delimitations methods to validate traditional, phenotype
      based species and circumscribe previously unrecognized species-level lineages in
      Montanelia. Relationships among putative lineages and divergence times were
      estimated within a coalescent-based multi-locus species tree framework. Based on
      the results of the species delimitation analyses, we propose that the genus
      Montanelia is likely comprised of six to nine species-level lineages, including
      previously unrecognized species-level diversity in the nominal taxa M.
      panniformis and M. tominii. In contrast, molecular sequence data suggest that M.
      predisjuncta may be conspecific with the widespread taxon M. disjuncta in spite
      of distinct morphological differences. The rate-based age estimation of the most
      recent common ancestor of Montanelia (ca. 23.1Ma) was similar to previous
      estimates based on the fossil record. Furthermore, our data suggest that
      diversification in Montanelia occurred largely during the Neogene. At least three
      Montanelia species are broadly distributed throughout Asia, Europe, and North
      America with no evidence of phylogeographic substructure. In contrast to broadly
      distributed Montanelia species, our study suggests Pleistocene-dominated
      diversification and complex biogeographic history in the M. tominii group. Our
      analyses provide additional insight for understanding diversification and
      uncovering cryptic diversity in cosmopolitan species of lichen-forming fungi. 

PMID- 25987533
TI  - T1 Hyperintensity of the Pediatric Neural Axis: What to Consider?

PMID- 25987534
TI  - Neonatal Pain and Infection Relate to Smaller Cerebellum in Very Preterm Children
      at School Age.
AB  - OBJECTIVE: To examine whether specific neonatal factors differentially influence
      cerebellar subregional volumes and to investigate relationships between
      subregional volumes and outcomes in very preterm children at 7 years of age.
      STUDY DESIGN: Fifty-six children born very preterm (24-32 weeks gestational age)
      followed longitudinally from birth underwent 3-dimensional T(1)-weighted
      neuroimaging at median age 7.6 years. Children with severe brain injury were
      excluded. Cerebellar subregions were automatically segmented using the multiple
      automatically generated templates algorithm. The relation between cerebellum
      subregional volumes (adjusted for total brain volume and sex) and neonatal
      clinical factors were examined using constrained principal component analysis.
      Cognitive and visual-motor integration functions in relation to cerebellar
      volumes were also investigated. RESULTS: Higher neonatal procedural pain and
      infection, as well as other clinical factors, were differentially associated with
      reduced cerebellar volumes in specific subregions. After adjusting for clinical
      risk factors, neonatal procedural pain was distinctively associated with smaller
      volumes bilaterally in the posterior VIIIA and VIIIB lobules. Specific smaller
      cerebellar subregional volumes were related to poorer cognition and motor/visual
      integration. CONCLUSIONS: In very preterm children, exposure to painful
      procedures, as well as additional neonatal risk factors such as infection, were
      associated with reduced cerebellar volumes in specific subregions and poorer
      outcomes at school age.

PMID- 25987535
TI  - Perioperative and Maintenance Therapy After First-Line Therapy as Paradigms for
      Drug Discovery in Urothelial Carcinoma.
AB  - Perioperative chemotherapy provided to increase the chance of cure for localized
      disease and maintenance therapy for metastatic disease represent 2 distinct
      aspects of the urothelial cancer disease treatment spectrum. The ability to
      access both pre- and postchemotherapy tissue in the neoadjuvant setting provides
      important opportunities for translational research to test novel therapies and
      identify predictors of response to therapy. The maintenance setting may be more
      complex, and study design and endpoints need to be determined on the basis of the
      candidate drugs' mechanisms of action and toxicity. 

PMID- 25987536
TI  - Salvage endoscopic nasopharyngectomy is superior to intensity-modulated radiation
      therapy for local recurrence of selected T1-T3 nasopharyngeal carcinoma - A case
      matched comparison.
AB  - BACKGROUND: Salvage ENPG and IMRT are more effective treatments for rNPC than
      traditional 2-dimensional radiotherapy. However, compared with IMRT, the benefits
      of ENPG have not yet been clearly described. METHODS: We defined a resectable
      area in which the disease could be radically removed using ENPG and our imaging
      specialists selected eligible patients with tumors confined to this resectable
      area from a database of rNPC patients. Using propensity scores to adjust for some
      potential prognostic factors, a well-balanced cohort of 144 limited rNPC patients
      was created by matching each patient who underwent ENPG (study group) with one
      who underwent IMRT (control group). Morbidity, long-term oncological results,
      treatment-related complications, medical costs, and quality of life were
      compared. RESULTS: Compared with IMRT, ENPG was associated with a relatively good
      overall survival (5-year OS, 77.1% vs 55.5%, P=.003), QOL conservation (mean
      global health status score, 57.6 vs 29.8, P<.001), and significant decreases in
      post-treatment complications (12.5% vs 65.3%, P<.001), medical costs (23 645.90
      vs 118 122.53 Yuan, P<.001)~(?2371.71 vs 11,847.80, P<.001). CONCLUSIONS: Salvage
      ENPG may be more effective for maximizing survival and QOL benefits and
      minimizing treatment-related complications and medical costs for limited rNPC
      patients, as compared with IMRT.

PMID- 25987537
TI  - Neuropsychological manifestations in children with Sydenham's chorea after
      adjunct intravenous immunoglobulin and standard treatment.
AB  - This was an exploratory study comparing neuropsychological manifestations of
      Sydenham's chorea (SC), 6 months after initiation of treatment, in children who
      had received intravenous immunoglobulins as an adjunct to standard treatment,
      with those who had received standard treatment. We included a non-SC control
      group for comparison. We hypothesized that compared to controls, children with SC
      who had received prior intravenous immunoglobulins would demonstrate less
      pronounced impairments compared to those who had received standard care. We
      conducted a cross-sectional analysis of 17 children with -SC who had received
      treatment 6 months previously (9 treated with standard of care and 8 augmented
      with intravenous immunoglobulins) and 17 non-SC, medically well controls. The
      standard treatment group (n = 9) exhibited significant behavioral difficulties,
      including significantly poorer co-operation (p = 0.009) compared with the other
      augmented immunoglobulins and non-SC control groups, and increased impulsivity (p
      = 0.016) compared with non-SC controls. The standard treatment group scored
      significantly lower than the other two groups on a measure of executive
      functioning (p = 0.03). Children with SC may be more at risk for
      neuropsychological difficulties than non-SC, medically well children. Intravenous
      immunoglobulins may mitigate some of these impairments.

PMID- 25987539
TI  - Maternally acquired IgG immunity in neonates born to renal transplanted women.
AB  - Neonates born to renal transplanted women are exposed in utero to
      immunosuppressors and to antenatal conditions that may predispose the neonate to
      a high risk of prematurity and intrauterine growth retardation. These factors
      might interfere with the transfer of maternal IgG immunity. Total IgG levels and
      specific antibodies to measles, varicella, tetanus, Haemophilus influenzae type b
      (Hib) and Streptococcus pneumoniae (serotypes 4,6B,9V,14,18C,19F and 23F) were
      evaluated on maternal and cord blood samples of 23 sets of renal transplanted
      women and their newborns and 32 sets of healthy women-newborns at term. Total IgG
      levels were measured by nephelometry and specific antibodies, by ELISA. Renal
      transplanted mothers had lower median tetanus antibodies (0.67IU/mL) than
      controls (1.53IU/mL; p=0.017). Neonates from renal transplanted mothers had lower
      median tetanus antibodies (0.95IU/mL) than controls (1.97IU/mL, p=0.008).
      Antibodies to measles, varicella, Hib and the 7 serotypes of S. pneumoniae were
      similar between groups. Maternal antibodies were associated with an increase in
      neonatal antibodies for all antigens; gestational age was associated with an
      increase in Hib neonatal antibodies. Preeclampsia was associated with a decrease
      in neonatal total IgG and serotype 4 S. pneumoniae antibodies; chronic
      hypertension was associated with a decrease in neonatal serotype 6B S. pneumoniae
      antibodies. As neonates from transplanted women may be born with lower tetanus
      antibodies than controls, efforts should be made to keep maternal vaccines up-to
      date. Clinical antenatal care with control of preeclampsia, chronic hypertension
      and prevention of premature delivery might also contribute to neonatal antibody
      levels to specific antigens at birth.

PMID- 25987540
TI  - Alterations in sucrose sham-feeding intake as a function of diet-exposure in rats
      maintained on calorically dense diets.
AB  - We previously reported that rats increase meal size upon initial presentation of
      a calorically dense diet. The increase may be attributed to increased orosensory
      stimulation and/or reduced sensitivity to post-ingestive inhibitory signals.
      During feeding both types of signals are simultaneously in play; thus here, we
      compare responses in rats presented a high-energy diet (HE) or 45% high-fat diet
      (HF) with those of chow-fed controls (CHOW) in a sham-feeding procedure in which
      post-ingestive feedback is minimized. Measures of sham-feeding to sucrose were
      taken before diet manipulation (baseline), ~5 days (dynamic phase) and ~6 weeks
      (static phase) following introduction of the palatable diet, as well as after
      animals were switched back to standard chow (recovery phase). Some but not all
      the hypotheses based on our previous findings were confirmed by the outcomes
      here. Consistent with our hypothesis that enhanced orosensory stimulation during
      the dynamic phase compared with the static phase would generalize to increased
      intake of other palatable stimuli, HE rats showed higher sucrose intake during
      the dynamic phase compared with the static phase. Contrary to what we
      hypothesized, HE and HF rats did not increase responses to sucrose compared to
      CHOW rats. In fact, HE rats showed decreased responses compared to CHOW controls.
      Thus changes in orosensory stimulation do not necessarily generalize to increased
      intake of other palatable stimuli. 

PMID- 25987541
TI  - Characterization of diabetic osteoarthritic cartilage and role of high glucose
      environment on chondrocyte activation: toward pathophysiological delineation of
      diabetes mellitus-related osteoarthritis.
AB  - OBJECTIVE: To examine the relationship between osteoarthritis (OA) and type 2
      diabetes mellitus (DM). METHODS: OA cartilage from DM and non-DM patients
      undergoing knee replacement were stimulated by IL-1beta for 24 h and release of
      interleukin-6 (IL-6) and prostaglandin E2 (PGE2) was measured. Primary cultured
      murine chondrocytes were stimulated for 24 and 72 h with or without IL-1beta (5
      ng/mL) under normal-glucose (5.5 mM) or high-glucose (25 mM) conditions. The
      expression and release of pro-inflammatory mediators (IL-6, cyclooxygenase 2
      [COX2]/PGE2) were analyzed by quantitative RT-PCR and ELISA/EIA. Glucose uptake
      was assessed with ((14)C)-2-deoxyglucose. Reactive oxygen species (ROS) and
      nitric oxide (NO) production were measured. To analyze the mechanism of IL-1beta
      induced inflammation, cells were pretreated or treated with inhibitors of glucose
      transport (cytochalasin B), the polyol pathway (epalrestat), mitochondrial
      oxidative stress (MitoTEMPO) or nitric oxide synthase (l-NAME). RESULTS: With IL
      1beta stimulation, IL-6 and PGE2 release was greater in human DM than non-DM OA
      cartilage (2.7- and 3-fold, respectively) (P < 0.05). In vitro, with IL-1beta
      stimulation, IL-6 and COX2 mRNA expression, IL-6 and PGE2 release, and ROS and NO
      production were greater under high-than normal-glucose conditions in cultured
      chondrocytes. IL-1beta-increased IL-6 release was reduced with cytochalasin B,
      epalrestat, L-NAME or MitoTEMPO treatment (-45%, -62%, -38% and -40%,
      respectively). CONCLUSION: OA cartilages from DM patients showed increased
      responsiveness to IL-1beta-induced inflammation. Accordingly, high glucose
      enhanced IL-1beta-induced inflammation in cultured chondrocytes via oxidative
      stress and the polyol pathway. High glucose and diabetes may thus participate in
      the increased inflammation in OA.

PMID- 25987542
TI  - Involvement of the CasK/R two-component system in optimal unsaturation of the
      Bacillus cereus fatty acids during low-temperature growth.
AB  - Bacillus cereus sensu lato is composed of a set of ubiquitous strains including
      human pathogens that can survive a range of food processing conditions, grow in
      refrigerated food, and sometimes cause food poisoning. We previously identified
      the two-component system CasK/R that plays a key role in cold adaptation. To
      better understand the CasK/R-controlled mechanisms that support low-temperature
      adaptation, we performed a transcriptomic analysis on the ATCC 14579 strain and
      its isogenic ?casK/R mutant grown at 12 degrees C. Several genes involved in
      fatty acid (FA) metabolism were downregulated in the mutant, including desA and
      desB encoding FA acyl-lipid desaturases that catalyze the formation of a double
      bond on the FA chain in positions ?5 and ?10, respectively. A lower proportion of
      FAs presumably unsaturated by DesA was observed in the DeltacasK/R strain
      compared to the parental strain while no difference was found for FAs presumably
      unsaturated by DesB. Addition of phospholipids from egg yolk lecithin rich in
      unsaturated FAs, to growth medium, abolished the cold-growth impairment of
      DeltacasK/R suggesting that exogenous unsaturated FAs can support membrane-level
      modifications and thus compensate for the decreased production of these FAs in
      the B. cereus ?casK/R mutant during growth at low temperature. Our findings
      indicate that CasK/R is involved in the regulation of FA metabolism, and is
      necessary for cold adaptation of B. cereus unless an exogenous source of
      unsaturated FAs is available. 

PMID- 25987538
TI  - Models and mechanisms of vascular dementia.
AB  - Vascular dementia (VaD) is the second leading form of dementia after Alzheimer's
      disease (AD) plaguing the elderly population. VaD is a progressive disease caused
      by reduced blood flow to the brain, and it affects cognitive abilities especially
      executive functioning. VaD is poorly understood and lacks suitable animal models,
      which constrain the progress on understanding the basis of the disease and
      developing treatments. This review article discusses VaD, its risk factors,
      induced cognitive disability, various animal (rodent) models of VaD, pathology,
      and mechanisms of VaD and treatment options. 

PMID- 25987543
TI  - Nebulette knockout mice have normal cardiac function, but show Z-line widening
      and up-regulation of cardiac stress markers.
AB  - AIMS: Nebulette is a 109 kDa modular protein localized in the sarcomeric Z-line
      of the heart. In vitro studies have suggested a role of nebulette in stabilizing
      the thin filament, and missense mutations in the nebulette gene were recently
      shown to be causative for dilated cardiomyopathy and endocardial fibroelastosis
      in human and mice. However, the role of nebulette in vivo has remained elusive.
      To provide insights into the function of nebulette in vivo, we generated and
      studied nebulette-deficient (nebl(-) (/-)) mice. METHODS AND RESULTS: Nebl(-) (/
      ) mice were generated by replacement of exon 1 by Cre under the control of the
      endogenous nebulette promoter, allowing for lineage analysis using the ROSA26 Cre
      reporter strain. This revealed specific expression of nebulette in the heart,
      consistent with in situ hybridization results. Nebl(-) (/-) mice exhibited normal
      cardiac function both under basal conditions and in response to transaortic
      constriction as assessed by echocardiography and haemodynamic analyses.
      Furthermore, histological, IF, and western blot analysis showed no cardiac
      abnormalities in nebl(-) (/-) mice up to 8 months of age. In contrast,
      transmission electron microscopy showed Z-line widening starting from 5 months of
      age, suggesting that nebulette is important for the integrity of the Z-line.
      Furthermore, up-regulation of cardiac stress responsive genes suggests the
      presence of chronic cardiac stress in nebl(-) (/-) mice. CONCLUSION: Nebulette is
      dispensable for normal cardiac function, although Z-line widening and up
      regulation of cardiac stress markers were found in nebl(-) (/-) heart. These
      results suggest that the nebulette disease causing mutations have dominant gain
      of-function effects.

PMID- 25987546
TI  - Development and trafficking function of haematopoietic stem cells and myeloid
      cells during fetal ontogeny.
AB  - Fetal haematopoiesis is a highly regulated process in terms of time and location.
      It is characterized by the emergence of specific cell populations at different
      extra- and intraembryonic anatomical sites. Trafficking of haematopoietic stem
      cells (HSCs) between these supportive niches is regulated by a set of molecules,
      i.e. integrins and chemokine receptors, which are also described for the
      recruitment of differentiated innate immune cells. In this review, an overview
      will be given on fetal haematopoiesis as well as trafficking of HSCs during fetal
      life. In addition, we will focus on the appearance of the first differentiated
      neutrophils and monocytes in the fetal circulation and describe how they acquire
      the ability to roll, adhere, and transmigrate into inflamed fetal tissue.
      Furthermore, we will discuss other effector functions of innate immune cells
      evolving during fetal ontogeny. 

PMID- 25987544
TI  - The regulation of transendothelial migration: new knowledge and new questions.
AB  - Leucocyte transendothelial migration (TEM) involves a co-operative series of
      interactions between surface molecules on the leucocyte and cognate counter
      ligands on the endothelial cell. These interactions set up a cascade of
      signalling events inside the endothelial cell that both allow for the junctions
      to loosen and for membrane to be recruited from the lateral border recycling
      compartment (LBRC). The LBRC is thought to provide an increased surface area and
      unligated receptors to the leucocyte to continue the process. The relative
      importance of the individual adhesion/signalling molecules that promote
      transmigration may vary depending on the type of leucocyte, the vascular bed, the
      inflammatory stimulus, and the stage of the inflammatory response. However, the
      molecular interactions between leucocyte and endothelial cell activate signalling
      pathways that disengage the adherens and tight junctions and recruit the LBRC to
      the site of transmigration. With the exception of disengaging the junctions,
      similar molecules and mechanisms promote transcellular migration as paracellular
      migration of leucocytes. This review will discuss the molecular interactions and
      signalling pathways that regulate transmigration, and the common themes that
      emerge from studying TEM of different leucocyte subsets under different
      inflammatory conditions. We will also raise some unanswered questions in need of
      future research. 

PMID- 25987547
TI  - Cancer-Directed Therapy and Hospice Care for Metastatic Cancer in American
      Indians and Alaska Natives.
AB  - BACKGROUND: Little has been reported regarding patterns of oncologic care in
      American Indian/Alaska Natives (AI/AN). Observed worse survival has been
      attributed to later-stage presentation. We aimed to evaluate racial differences
      in cancer-directed therapy and hospice care utilization in AI/ANs and non
      Hispanic whites (NHW) with metastatic cancer. METHODS: The linked Surveillance,
      Epidemiology, and End Results (SEER)-Medicare claims database was accessed for
      AI/AN and NHW metastatic-cancer cases diagnosed between 2001 and 2007.
      Utilization of cancer-directed therapy (surgery, radiation, and/or chemotherapy)
      and/or hospice services was compared between AI/ANs and NHWs. Minimally adjusted
      (age, sex, diagnosis year) and fully-adjusted (also Klabunde comorbidity score,
      sociodemographic factors) regression models were used to estimate odds (OR) and
      hazard ratios (HR) for receipt of care. RESULTS: AI/ANs were younger, more likely
      to reside in the West, be unmarried, have lower income, and live in a nonurban
      setting than NHWs. Fewer AI/ANs received any cancer-directed therapy (57% vs. 61%
      NHWs) within 3 months of diagnosis; sociodemographic factors accounted for much
      of this difference [fully-adjusted HR, 0.94; 95% confidence interval (CI), 0.83
      1.08]. We noted differences in hospice utilization between AI/ANs (52%) and NHWs
      (61%). A significant difference in hospice utilization remained after adjustment
      for sociodemographics (OR, 0.78; 95% CI, 0.61-0.99). CONCLUSION: Observed
      absolute differences in care for AI/ANs and NHWs with metastatic cancer were
      largely accounted for by adjusting for socioeconomics, comorbidities, and
      demographic factors. A significant association between race and hospice
      utilization was noted. IMPACT: Efforts to improve metastatic-cancer care should
      focus on socioeconomic barriers and investigate the observed disparity in receipt
      of hospice services.

PMID- 25987545
TI  - Modulation of cardiac fibrosis by Kruppel-like factor 6 through transcriptional
      control of thrombospondin 4 in cardiomyocytes.
AB  - AIMS: Kruppel-like factors (KLFs) are a family of transcription factors which
      play important roles in the heart under pathological and developmental
      conditions. We previously identified and cloned Klf6 whose homozygous mutation in
      mice results in embryonic lethality suggesting a role in cardiovascular
      development. Effects of KLF6 on pathological regulation of the heart were
      investigated in the present study. METHODS AND RESULTS: Mice heterozygous for
      Klf6 resulted in significantly diminished levels of cardiac fibrosis in response
      to angiotensin II infusion. Intriguingly, a similar phenotype was seen in
      cardiomyocyte-specific Klf6 knockout mice, but not in cardiac fibroblast-specific
      knockout mice. Microarray analysis revealed increased levels of the extracellular
      matrix factor, thrombospondin 4 (TSP4), in the Klf6-ablated heart.
      Mechanistically, KLF6 directly suppressed Tsp4 expression levels, and cardiac
      TSP4 regulated the activation of cardiac fibroblasts to regulate cardiac
      fibrosis. CONCLUSION: Our present studies on the cardiac function of KLF6 show a
      new mechanism whereby cardiomyocytes regulate cardiac fibrosis through
      transcriptional control of the extracellular matrix factor, TSP4, which, in turn,
      modulates activation of cardiac fibroblasts.

PMID- 25987549
TI  - An in vitro evaluation of gaseous microemboli handling by contemporary venous
      reservoirs and oxygenator systems using EDAC.
AB  - Gaseous microemboli (GME) generated during cardiopulmonary bypass (CPB) can
      present a significant risk to patient outcomes, specifically if they are
      delivered to the cerebral vasculature. A number of GME sources have been
      identified, leading to improved clinical practice and equipment design to
      ameliorate the presence and intensity of GME during CPB. Recently, a number of
      new venous reservoir/oxygenator systems have entered the market, including the
      Sorin Inspire6 and Inspire8, the Terumo FX15 and FX25 and the Maquet Quadrox-i.
      The goal of the current study was to evaluate the GME-handling capacity of these
      contemporary venous reservoirs, oxygenators and complete systems, as well as our
      currently used Sorin Synthesis, using the EDAC system. The venous reservoir of
      the Quadrox-i was the most effective in removing all sizes of GME and total GME
      load, while the Synthesis was the least effective. The FX15 and FX25 were least
      effective removing small GME, while the FX15 and Quadrox-i were the least
      effective at removing medium GME. The Quadrox-i was least effective at removing
      large GME. In terms of complete venous reservoir/oxygenator systems, the
      Synthesis permitted the greatest amount of GME to pass, while the other systems
      appeared largely equivalent. 

PMID- 25987548
TI  - Normal Taste Acceptance and Preference of PANX1 Knockout Mice.
AB  - Taste compounds detected by G protein-coupled receptors on the apical surface of
      Type 2 taste cells initiate an intracellular molecular cascade culminating in the
      release of ATP. It has been suggested that this ATP release is accomplished by
      pannexin 1 (PANX1). However, we report here that PANX1 knockout mice do not
      differ from wild-type controls in response to representative taste solutions,
      measured using 5-s brief-access tests or 48-h two-bottle choice tests. This
      implies that PANX1 is unnecessary for taste detection and consequently that ATP
      release from Type 2 taste cells does not require PANX1. 

PMID- 25987550
TI  - Adenosine regulation of the immune response initiated by ischemia reperfusion
      injury.
AB  - It is clinically established that adenosine has negative chronotropic,
      antiarrhythmic effects and reduces arterial blood pressure. Adenosine addition to
      cardioplegic solutions used in cardiac operations is clinically well tolerated
      and has been shown to improve myocardial protection in several studies. However,
      the mechanism of action remains unclear. Therefore, it is important to define the
      effect of adenosine on the inflammatory cascade as immune cell activation occurs
      early during ischemia reperfusion injury. Adenosine appears to mediate the
      initial steps of the inflammatory cascade via its four G-coupled protein
      receptors: A1, A2A, A2B, and A3, expressed on neutrophils, lymphocytes and
      macrophages. The adenosine receptor isotype dictates the immune response. More
      specifically, the A1 and A3 receptors stimulate a pro-inflammatory immune
      response whereas the A2A and A2B are immunosuppressive. As the adenosine
      receptors are important for cardiac pre-conditioning and post-conditioning,
      adenosine may regulate the inflammatory responses initiated during ischemia
      mediated immune injury related to myocardial protection. 

PMID- 25987551
TI  - Hydrodynamic evaluation of aortic cardiopulmonary bypass cannulae using particle
      image velocimetry.
AB  - The high velocity jet from aortic arterial cannulae used during cardiopulmonary
      bypass potentially causes a "sandblasting" injury to the aorta, increasing the
      possibility of embolisation of atheromatous plaque. We investigated a range of
      commonly available dispersion and non-dispersion cannulae, using particle image
      velocimetry. The maximum velocity of the exit jet was assessed 20 and 40 mm from
      the cannula tip at flow rates of 3 and 5 L/min. The dispersion cannulae had lower
      maximum velocities compared to the non-dispersion cannulae. Dispersion cannulae
      had fan-shaped exit profiles and maximum velocities ranged from 0.63 to 1.52 m/s
      when measured at 20 mm and 5 L/min. Non-dispersion cannulae had maximum
      velocities ranging from 1.52 to 3.06 m/s at 20 mm and 5 L/min, with corresponding
      narrow velocity profiles. This study highlights the importance of understanding
      the hydrodynamic performance of these cannulae as it may help in selecting the
      most appropriate cannula to minimize the risk of thromboembolic events or aortic
      injury. 

PMID- 25987552
TI  - Extracorporeal life support for massive pulmonary embolism during pregnancy.
AB  - Massive pulmonary embolism is a leading cause of death during pregnancy. While
      the prevention of thromboembolic disease during the peripartum period is
      codified, there is no consensus regarding its treatment. We report two cases of
      pregnant women who had massive pulmonary embolisms (PE) and shock treated with
      veno-arterial extracorporeal life support (ECLS) and heparin therapy.Haemodynamic
      and oxygenation parameters were rapidly restored. The patients completely
      recovered and the pregnancies continued. The patients did not develop pulmonary
      hypertension. ECLS can be considered as a successful treatment option of massive
      pulmonary embolism during pregnancy. 

PMID- 25987553
TI  - Development and Validation of a Method for Simultaneous Estimation of Metformin
      and Sitagliptin in Human Plasma by LC-MS-MS and Its Application in a
      Bioequivalence Study.
AB  - A simple, sensitive, precise and accurate method for simultaneous estimation of
      metformin and sitagliptin from human plasma was developed and validated. Samples
      extracted from plasma using acetonitrile were separated on an SCX column and
      estimated using API 4000 Mass Spectrometer in the positive atmospheric pressure
      ionization mode (Turboionspray) by following multiple reaction monitoring
      transitions for both parent and daughter ions. A linear calibration plot was
      achieved for both the analytes in the concentration ranges of 10-2,206 ng/mL (for
      metformin) and 3-800.5 ng/mL (for sitagliptin) prepared in K2EDTA pooled plasma.
      Mean recovery for metformin was 92% and for sitagliptin was 104.5%. It is a fully
      validated method and successfully applied for estimation of these drug molecules
      during biostudies. 

PMID- 25987554
TI  - The Paradox of Humiliation: The Acceptance of an Unjust Devaluation of the Self.
AB  - Despite growing attention the study of humiliation is receiving, there is little
      consensus as to how humiliation differs from other related emotions. We here
      argue that humiliation shares central characteristics with anger, shame, and
      embarrassment, but also differs from these emotions in meaningful ways. In Study
      1, participants read about a professor who demeaned a student's work. We
      manipulated key appraisals of this scenario and measured humiliation, shame,
      anger, and embarrassment, as well as the tendencies for approach and avoidance.
      Results indicated that humiliation arises from accepting a devaluation of the
      self, which, simultaneously, is appraised as unjust. Moreover, humiliation is
      associated with tendencies for approach and avoidance simultaneously. We
      replicated these results in Study 2 in which participants referred to actual
      experiences in their lives during which they felt humiliated, ashamed, or angry.
      Taken together, results provide evidence of the unique nature of humiliation as a
      distinct, self-conscious emotion. 

PMID- 25987558
TI  - DNA Polymerase alpha Subunit Residues and Interactions Required for Efficient
      Initiation Complex Formation Identified by a Genetic Selection.
AB  - Biophysical and structural studies have defined many of the interactions that
      occur between individual components or subassemblies of the bacterial replicase,
      DNA polymerase III holoenzyme (Pol III HE). Here, we extended our knowledge of
      residues and interactions that are important for the first step of the replicase
      reaction: the ATP-dependent formation of an initiation complex between the Pol
      III HE and primed DNA. We exploited a genetic selection using a dominant negative
      variant of the polymerase catalytic subunit that can effectively compete with
      wild-type Pol III alpha and form initiation complexes, but cannot elongate.
      Suppression of the dominant negative phenotype was achieved by secondary
      mutations that were ineffective in initiation complex formation. The
      corresponding proteins were purified and characterized. One class of mutant
      mapped to the PHP domain of Pol III alpha, ablating interaction with the epsilon
      proofreading subunit and distorting the polymerase active site in the adjacent
      polymerase domain. Another class of mutation, found near the C terminus,
      interfered with tau binding. A third class mapped within the known beta-binding
      domain, decreasing interaction with the beta2 processivity factor. Surprisingly,
      mutations within the beta binding domain also ablated interaction with tau,
      suggesting a larger tau binding site than previously recognized. 

PMID- 25987559
TI  - Cytosolic PTEN-induced Putative Kinase 1 Is Stabilized by the NF-kappaB Pathway
      and Promotes Non-selective Mitophagy.
AB  - The potential cellular function of the 53-kDa cytosolic form of PINK1 (PINK1-53)
      is often overlooked because of its rapid degradation by the proteasome upon its
      production. Although a number of recent studies have suggested various roles for
      PINK1-53, how this labile PINK1 species attains an adequate expression level to
      fulfil these roles remains unclear. Here we demonstrated that PINK1-53 is
      stabilized in the presence of enhanced Lys-63-linked ubiquitination and
      identified TRAF6-related NF-kappaB activation as a novel pathway involved in
      this. We further showed that a mimetic of PINK1-53 promotes mitophagy but,
      curiously, in apparently healthy mitochondria. We speculate that this "non
      selective" form of mitophagy may potentially help to counteract the build-up of
      reactive oxygen species in cells undergoing oxidative stress and, as such,
      represent a cytoprotective response. 

PMID- 25987560
TI  - Minimalist Model Systems Reveal Similarities and Differences between Membrane
      Interaction Modes of MCL1 and BAK.
AB  - Proteins belonging to the BCL2 family are key modulators of apoptosis that
      establish a complex network of interactions among themselves and with other
      cellular factors to regulate cell fate. It is well established that mitochondrial
      membranes are the main locus of action of all BCL2 family proteins, but it is
      difficult to obtain a precise view of how BCL2 family members operate at the
      native mitochondrial membrane environment during apoptosis. Here, we used
      minimalist model systems and multiple fluorescence-based techniques to examine
      selected membrane activities of MCL1 and BAK under apoptotic-like conditions. We
      show that three distinct apoptosis-related factors (i.e. the BCL2 homology 3
      ligand cBID, the mitochondrion-specific lipid cardiolipin, and membrane
      geometrical curvature) all promote membrane association of BCL2-like structural
      folds belonging to both MCL1 and BAK. However, at the same time, the two proteins
      exhibited distinguishing features in their membrane association modes under
      apoptotic-like conditions. In addition, scanning fluorescence cross-correlation
      spectroscopy and FRET measurements revealed that the BCL2-like structural fold of
      MCL1, but not that of BAK, forms stable heterodimeric complexes with cBID in a
      manner adjustable by membrane cardiolipin content and curvature degree. Our
      results add significantly to a growing body of evidence indicating that the
      mitochondrial membrane environment plays a complex and active role in the mode of
      action of BCL2 family proteins. 

PMID- 25987561
TI  - Palmitoleate Reverses High Fat-induced Proinflammatory Macrophage Polarization
      via AMP-activated Protein Kinase (AMPK).
AB  - A rise in tissue-embedded macrophages displaying "M1-like" proinflammatory
      polarization is a hallmark of metabolic inflammation during a high fat diet or
      obesity. Here we show that bone marrow-derived macrophages (BMDM) from high fat
      fed mice retain a memory of their dietary environment in vivo (displaying the
      elevated proinflammatory genes Cxcl1, Il6, Tnf, Nos2) despite 7-day
      differentiation and proliferation ex vivo. Notably, 6-h incubation with
      palmitoleate (PO) reversed the proinflammatory gene expression and cytokine
      secretion seen in BMDM from high fat-fed mice. BMDM from low fat-fed mice exposed
      to palmitate (PA) for 18 h ex vivo also showed elevated expression of
      proinflammatory genes (Cxcl1, Il6, Tnf, Nos2, and Il12b) associated with M1
      polarization. Conversely, PO treatment increased anti-inflammatory genes (Mrc1,
      Tgfb1, Il10, Mgl2) and oxidative metabolism, characteristic of M2 macrophages.
      Therefore, saturated and unsaturated fatty acids bring about opposite macrophage
      polarization states. Coincubation of BMDM with both fatty acids counteracted the
      PA-induced Nos2 expression in a PO dose-dependent fashion. PO also prevented PA
      induced IkappaBalpha degradation, RelA nuclear translocation, NO production, and
      cytokine secretion. Mechanistically, PO exerted its anti-inflammatory function
      through AMP-activated protein kinase as AMP kinase knockout or inhibition by
      Compound C offset the PO-dependent prevention of PA-induced inflammation. These
      results demonstrate a nutritional memory of BMDM ex vivo, highlight the
      plasticity of BMDM polarization in response to saturated and unsaturated fatty
      acids, and identify the potential to reverse diet- and saturated fat-induced M1
      like polarization by administering palmitoleate. These findings could have
      applicability to reverse obesity-linked inflammation in metabolically relevant
      tissues. 

PMID- 25987562
TI  - Resveratrol and SRT1720 Elicit Differential Effects in Metabolic Organs and
      Modulate Systemic Parameters Independently of Skeletal Muscle Peroxisome
      Proliferator-activated Receptor gamma Co-activator 1alpha (PGC-1alpha).
AB  - Resveratrol (RSV) and SRT1720 (SRT) elicit beneficial metabolic effects and are
      postulated to ameliorate obesity and related metabolic complications. The co
      activator, peroxisome proliferator-activated receptor gamma co-activator 1alpha
      (PGC-1alpha), has emerged as a major downstream effector responsible for
      metabolic remodeling of muscle and other metabolic tissues in response to RSV or
      SRT treatment. However, the requirement of PGC-1alpha in skeletal muscle for the
      systemic metabolic effects of these compounds has so far not been demonstrated.
      Using muscle-specific PGC-1alpha knock-out mice, we show that PGC-1alpha is
      necessary for transcriptional induction of mitochondrial genes in muscle with
      both RSV and SRT treatment. Surprisingly, the beneficial effects of SRT on
      glucose homeostasis and of both compounds on energy expenditure occur even in the
      absence of muscle PGC-1alpha. Moreover, RSV and SRT treatment elicit differential
      transcriptional effects on genes involved in lipid metabolism and mitochondrial
      biogenesis in liver and adipose tissue. These findings indicate that RSV and SRT
      do not induce analogous metabolic effects in vivo. Our results provide important
      insights into the mechanism, effects, and organ specificity of the caloric
      restriction mimetics RSV and SRT. These findings are important for the design of
      future therapeutic interventions aimed at ameliorating obesity and obesity
      related metabolic dysfunction. 

PMID- 25987563
TI  - Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B.
AB  - Aurora kinase A and B share great similarity in sequences, structures, and
      phosphorylation motif, yet they show different localizations and play distinct
      crucial roles. The factors that determine such differences are largely unknown.
      Here we targeted Aurora A to the localization of Aurora B and found that Aurora A
      phosphorylates the substrate of Aurora B and substitutes its function in spindle
      checkpoint. In return, the centrosome targeting of Aurora B substitutes the
      function of Aurora A in the mitotic entry. Expressing the chimera proteins of the
      Auroras with exchanged N termini in cells indicates that the divergent N termini
      are also important for their spatiotemporal localizations and functions.
      Collectively, we demonstrate that functional divergence of Aurora kinases is
      determined by spatial compartmentalization, and their divergent N termini also
      contribute to their spatial and functional differentiation. 

PMID- 25987564
TI  - Pim-2 Kinase Influences Regulatory T Cell Function and Stability by Mediating
      Foxp3 Protein N-terminal Phosphorylation.
AB  - Regulation of the extent of immune responses is a requirement to maintain self
      tolerance and limit inflammatory processes. CD4(+)CD25(+)Foxp3(+) regulatory T
      (Treg) cells play a role in regulation. The Foxp3 transcription factor is
      considered a dominant regulator for Treg cell development and function. Foxp3
      function itself is directly regulated by multiple posttranslational modifications
      that occur in response to various external stimuli. The Foxp3 protein is a
      component of several dynamic macromolecular regulatory complexes. The complexes
      change constituents over time and through different signals to regulate the
      development and function of regulatory T cells. Here we identified a mechanism
      regulating Foxp3 level and activity that operates through discrete
      phosphorylation. The Pim-2 kinase can phosphorylate Foxp3, leading to decreased
      suppressive functions of Treg cells. The amino-terminal domain of Foxp3 is
      modified at several sites by Pim-2 kinase. This modification leads to altered
      expression of proteins related to Treg cell functions and increased Treg cell
      lineage stability. Treg cell suppressive function can be up-regulated by either
      pharmacologically inhibiting Pim-2 kinase activity or by genetically knocking out
      Pim-2 in rodent Treg cells. Deficiency of Pim-2 activity increases murine host
      resistance to dextran sodium sulfate-induced colitis in vivo, and a Pim-2 small
      molecule kinase inhibitor also modified Treg cell functions. Our studies define a
      pathway for limiting the regulation of Foxp3 function because the Pim-2 kinase
      represents a potential therapeutic target for modulating the Treg cell
      suppressive activities in controlling immune responses. 

PMID- 25987566
TI  - Mechanisms in endocrinology: The spectrum of haemostatic abnormalities in
      glucocorticoid excess and defect.
AB  - Glucocorticoids (GCs) target several components of the integrated system that
      preserves vascular integrity and free blood flow. Cohort studies on Cushing's
      syndrome (CS) have revealed increased thromboembolism, but the pathogenesis
      remains unclear. Lessons from epidemiological data and post-treatment
      normalisation time suggest a bimodal action with a rapid and reversible effect on
      coagulation factors and an indirect sustained effect on the vessel wall. The
      redundancy of the steps that are potentially involved requires a systematic
      comparison of data from patients with endogenous or exogenous hypercortisolism in
      the context of either inflammatory or non-inflammatory disorders. A predominant
      alteration in the intrinsic pathway that includes a remarkable rise in factor
      VIII and von Willebrand factor (vWF) levels and a reduction in activated partial
      thromboplastin time appears in the majority of studies on endogenous CS. There
      may also be a rise in platelets, thromboxane B2, thrombin-antithrombin complexes
      and fibrinogen (FBG) levels and, above all, impaired fibrinolytic capacity. The
      increased activation of coagulation inhibitors seems to be compensatory in order
      to counteract disseminated coagulation, but there remains a net change towards an
      increased risk of venous thromboembolism (VTE). Conversely, GC administered in
      the presence of inflammation lowers vWF and FBG, but fibrinolytic activity is
      also reduced. As a result, the overall risk of VTE is increased in long-term
      users. Finally, no studies have assessed haemostatic abnormalities in patients
      with Addison's disease, although these may present as a consequence of bilateral
      adrenal haemorrhage, especially in the presence of antiphospholipid antibodies or
      anticoagulant treatments. The present review aimed to provide a comprehensive
      overview of the complex alterations produced by GCs in order to develop better
      screening and prevention strategies against bleeding and thrombosis. 

PMID- 25987565
TI  - The Transmission Interfaces Contribute Asymmetrically to the Assembly and
      Activity of Human P-glycoprotein.
AB  - P-glycoprotein (P-gp; ABCB1) is an ABC drug pump that protects us from toxic
      compounds. It is clinically important because it confers multidrug resistance.
      The homologous halves of P-gp each contain a transmembrane (TM) domain (TMD) with
      6 TM segments followed by a nucleotide-binding domain (NBD). The drug- and ATP
      binding sites reside at the interface between the TMDs and NBDs, respectively.
      Each NBD is connected to the TMDs by a transmission interface involving a pair of
      intracellular loops (ICLs) that form ball-and-socket joints. P-gp is different
      from CFTR (ABCC7) in that deleting NBD2 causes misprocessing of only P-gp.
      Therefore, NBD2 might be critical for stabilizing ICLs 2 and 3 that form a
      tetrahelix bundle at the NBD2 interface. Here we report that the NBD1 and NBD2
      transmission interfaces in P-gp are asymmetric. Point mutations to 25 of 60
      ICL2/ICL3 residues at the NBD2 transmission interface severely reduced P-gp
      assembly while changes to the equivalent residues in ICL1/ICL4 at the NBD1
      interface had little effect. The hydrophobic nature at the transmission
      interfaces was also different. Mutation of Phe-1086 or Tyr-1087 to arginine at
      the NBD2 socket blocked activity or assembly while the equivalent mutations at
      the NBD1 socket had only modest effects. The results suggest that the NBD
      transmission interfaces are asymmetric. In contrast to the ICL2/3-NBD2 interface,
      the ICL1/4-NBD1 transmission interface is more hydrophilic and insensitive to
      mutations. Therefore the ICL2/3-NBD2 transmission interface forms a precise
      hydrophobic connection that acts as a linchpin for assembly and trafficking of P
      gp. 

PMID- 25987567
TI  - IMSEQ--a fast and error aware approach to immunogenetic sequence analysis.
AB  - MOTIVATION: Recombined T- and B-cell receptor repertoires are increasingly being
      studied using next generation sequencing (NGS) in order to interrogate the
      repertoire composition as well as changes in the distribution of receptor clones
      under different physiological and disease states. This type of analysis requires
      efficient and unambiguous clonotype assignment to a large number of NGS read
      sequences, including the identification of the incorporated V and J gene segments
      and the CDR3 sequence. Current tools have deficits with respect to performance,
      accuracy and documentation of their underlying algorithms and usage. RESULTS: We
      present IMSEQ, a method to derive clonotype repertoires from NGS data with
      sophisticated routines for handling errors stemming from PCR and sequencing
      artefacts. The application can handle different kinds of input data originating
      from single- or paired-end sequencing in different configurations and is generic
      regarding the species and gene of interest. We have carefully evaluated our
      method with simulated and real world data and show that IMSEQ is superior to
      other tools with respect to its clonotyping as well as standalone error
      correction and runtime performance. AVAILABILITY AND IMPLEMENTATION: IMSEQ was
      implemented in C++ using the SeqAn library for efficient sequence analysis. It is
      freely available under the GPLv2 open source license and can be downloaded at
      www.imtools.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online. CONTACT: lkuchenb@inf.fu-berlin.de or
      peter.robinson@charite.de.

PMID- 25987568
TI  - TRAL: tandem repeat annotation library.
AB  - MOTIVATION: Currently, more than 40 sequence tandem repeat detectors are
      published, providing heterogeneous, partly complementary, partly conflicting
      results. RESULTS: We present TRAL, a tandem repeat annotation library that allows
      running and parsing of various detection outputs, clustering of redundant or
      overlapping annotations, several statistical frameworks for filtering false
      positive annotations, and importantly a tandem repeat annotation and refinement
      module based on circular profile hidden Markov models (cpHMMs). Using TRAL, we
      evaluated the performance of a multi-step tandem repeat annotation workflow on
      547 085 sequences in UniProtKB/Swiss-Prot. The researcher can use these results
      to predict run-times for specific datasets, and to choose annotation complexity
      accordingly. AVAILABILITY AND IMPLEMENTATION: TRAL is an open-source Python 3
      library and is available, together with documentation and tutorials via
      http://www.vital-it.ch/software/tral. CONTACT: elke.schaper@isb-sib.ch.

PMID- 25987570
TI  - Reverse intersystem crossing from upper triplet levels to excited singlet: a 'hot
      excition' path for organic light-emitting diodes.
AB  - Since researches on the fate of highly excited triplet states demonstrated the
      existence of reverse intersystem crossing (RISC) from upper triplet levels to
      singlet manifold in naphthalene, quinoline, isoquinoline, etc. in the 1960s, this
      unique photophysical process was then found and identified in some other aromatic
      materials. However, the early investigations mainly focus on exploring the
      mechanism of this photophysical process; no incorporation of specific application
      was implemented. Until recently, our group innovatively used this 'sleeping'
      photophysical process to enhance the efficiency of fluorescent organic light
      emitting diodes by simultaneously harvesting singlet and triplet excitons.
      Efforts are devoted to developing materials with high photoluminescence
      efficiency and effective RISC through appropriate molecular design in a series of
      donor-acceptor material systems. The experimental and theoretical results
      indicate that these materials exhibit hybridized local and charge-transfer
      excited state, which achieve a combination of the high radiation from local
      excited state and the high T(m)->S(n) (m>=2, n>=1) conversion along charge
      transfer excited state. As expected, the devices exhibited favourable external
      quantum efficiency and low roll-off, and especially an exciton utilization
      efficiency exceeding the limit of 25%. Considering the significant progress made
      in organic light-emitting diodes with this photophysical process, we review the
      relevant mechanism and material systems, as well as our design principle in
      materials and device application.

PMID- 25987569
TI  - Serial monitoring of circulating tumor DNA in patients with primary breast cancer
      for detection of occult metastatic disease.
AB  - Metastatic breast cancer is usually diagnosed after becoming symptomatic, at
      which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA)
      contains tumor-specific chromosomal rearrangements that may be interrogated in
      blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of
      metastasis in a retrospective study of 20 patients diagnosed with primary breast
      cancer and long follow-up. Using an approach combining low-coverage whole-genome
      sequencing of primary tumors and quantification of tumor-specific rearrangements
      in plasma by droplet digital PCR, we identify for the first time that ctDNA
      monitoring is highly accurate for postsurgical discrimination between patients
      with (93%) and without (100%) eventual clinically detected recurrence. ctDNA
      based detection preceded clinical detection of metastasis in 86% of patients with
      an average lead time of 11 months (range 0-37 months), whereas patients with long
      term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity
      was predictive of poor survival. These findings establish the rationale for
      larger validation studies in early breast cancer to evaluate ctDNA as a
      monitoring tool for early metastasis detection, therapy modification, and to aid
      in avoidance of overtreatment. 

PMID- 25987571
TI  - Photon upconversion sensitized by a Ru(II)-pyrenyl chromophore.
AB  - The near-visible-to-blue singlet fluorescence of anthracene sensitized by a
      ruthenium chromophore with a long-lived triplet-excited state, [Ru(5-pyrenyl-1,10
      phenanthroline)(3)](PF(6))(2), in acetonitrile was investigated. Low intensity
      non-coherent green light was used to selectively excite the sensitizer in the
      presence of micromolar concentrations of anthracene generating anti-Stokes,
      singlet fluorescence in the latter, even with incident power densities below 500
      MUW cm(-2). The resultant data are consistent with photon upconversion proceeding
      from sensitized triplet-triplet annihilation (TTA) of the anthracene acceptor
      molecules, confirmed through transient absorption spectroscopy as well as static
      and dynamic photoluminescence experiments. Additionally, quadratic-to-linear
      incident power regimes for the upconversion process were identified for this
      composition under monochromatic 488 nm excitation, consistent with a sensitized
      TTA mechanism ultimately producing the anti-Stokes emission characteristic of
      anthracene singlet fluorescence.

PMID- 25987572
TI  - Excitons and the lifetime of organic semiconductor devices.
AB  - While excitons are responsible for the many beneficial optical properties of
      organic semiconductors, their non-radiative recombination within the material can
      result in material degradation due to the dumping of energy onto localized
      molecular bonds. This presents a challenge in developing strategies to exploit
      the benefits of excitons without negatively impacting the device operational
      stability. Here, we will briefly review the fundamental mechanisms leading to
      excitonic energy-driven device ageing in two example devices: blue emitting
      electrophosphorescent organic light emitting devices (PHOLEDs) and organic
      photovoltaic (OPV) cells. We describe strategies used to minimize or even
      eliminate this fundamental device degradation pathway. 

PMID- 25987573
TI  - Magnetic field dependence of singlet fission in solutions of diphenyl tetracene.
AB  - Magnetic field effects provide a convenient and specific probe of singlet exciton
      fission within optoelectronic devices. Here, we demonstrate that this tool may
      also be applied to screen potential fission material candidates in solution. We
      characterize the phenomenon in diphenyl tetracene (DPT), which shows strong
      fluorescence modulation and the expected field dependence in its transient decay
      as a function of concentration. Solution measurements may also be used to test
      for the presence of an intermediate charge transfer state, but we observe no
      changes to the field dependence of DPT singlet exciton fission in toluene
      relative to chloroform. 

PMID- 25987574
TI  - Triplet-triplet annihilation in highly efficient fluorescent organic light
      emitting diodes: current state and future outlook.
AB  - Studies of delayed electroluminescence in highly efficient fluorescent organic
      light-emitting diodes (OLEDs) of many dissimilar architectures indicate that the
      triplet-triplet annihilation (TTA) significantly increases yield of excited
      singlet states-emitting molecules in this type of device thereby contributes
      substantially to their efficiency. Towards the end of the 2000s, the essential
      role of TTA in realizing highly efficient fluorescent devices was widely
      recognized. Analysis of a diverse set of fluorescent OLEDs shows that high
      efficiencies are often cor-related to TTA extents. It is therefore likely that it
      is the long-term empirical optimization of OLED efficiencies that has resulted in
      fortuitous emergence of TTA as a large and ubiquitous contributor to efficiency.
      TTA contributions as high as 20-30% are common in the state-of-the-art OLEDs, and
      even become dominant in special cases, where TTA is shown to substantially exceed
      the spin-statistical limit. The fundamental features of OLED efficiency
      enhancement via TTA-molecular structure-dependent contributions, current density
      dependent intensities in practical devices and frequently observed antagonistic
      relationships between TTA extent and OLED lifetime-came to be understood over the
      course of the next few years. More recently, however, there was much less
      reported progress with respect to all-important quantitative details of the TTA
      mechanism. It should be emphasized that, to this day and despite the decades of
      work on improving blue phosphorescent OLEDs as well as the recent advent of
      thermally activated delayed fluorescence OLEDs, the majority of practical blue
      OLEDs still rely on TTA. Considering such practical importance of fluorescent
      blue OLEDs, the design of blue OLED-compatible materials capable of substantially
      exceeding the spin-statistical limit in TTA, elimination of the antagonistic
      relationship between TTA-related efficiency gains and lifetime losses, and
      designing devices with an extended range of current densities producing near
      maximum TTA electroluminescence are the areas where future improvements would be
      most beneficial. 

PMID- 25987575
TI  - Singlet-to-triplet interconversion using hyperfine as well as ferromagnetic
      fringe fields.
AB  - Until recently the important role that spin-physics ('spintronics') plays in
      organic light-emitting devices and photovoltaic cells was not sufficiently
      recognized. This attitude has begun to change. We review our recent work that
      shows that spatially rapidly varying local magnetic fields that may be present in
      the organic layer dramatically affect electronic transport properties and
      electroluminescence efficiency. Competition between spin-dynamics due to these
      spatially varying fields and an applied, spatially homogeneous magnetic field
      leads to large magnetoresistance, even at room temperature where the
      thermodynamic influences of the resulting nuclear and electronic Zeeman
      splittings are negligible. Spatially rapidly varying local magnetic fields are
      naturally present in many organic materials in the form of nuclear hyperfine
      fields, but we will also review a second method of controlling the electrical
      conductivity/electroluminescence, using the spatially varying magnetic fringe
      fields of a magnetically unsaturated ferromagnet. Fringe-field magnetoresistance
      has a magnitude of several per cent and is hysteretic and anisotropic. This new
      method of control is sensitive to even remanent magnetic states, leading to
      different conductivity/electroluminescence values in the absence of an applied
      field. We briefly review a model based on fringe-field-induced polaron-pair spin
      dynamics that successfully describes several key features of the experimental
      fringe-field magnetoresistance and magnetoelectroluminescence. 

PMID- 25987576
TI  - Singlet fission of hot excitons in pi-conjugated polymers.
AB  - We used steady-state photoinduced absorption (PA), excitation dependence
      (EXPA(omega)) spectrum of the triplet exciton PA band, and its magneto-PA
      (MPA(B)) response to investigate singlet fission (SF) of hot excitons into two
      separated triplet excitons, in two luminescent and non-luminescent pi-conjugated
      polymers. From the high energy step in the triplet EXPA(omega) spectrum of the
      luminescent polymer poly(dioctyloxy)phenylenevinylene (DOO-PPV) films, we
      identified a hot-exciton SF (HE-SF) process having threshold energy at E~2E(T)
      (=2.8 eV, where ET is the energy of the lowest lying triplet exciton), which is
      about 0.8 eV above the lowest singlet exciton energy. The HE-SF process was
      confirmed by the triplet MPA(B) response for excitation at E>2E(T), which shows
      typical SF response. This process is missing in DOO-PPV solution, showing that it
      is predominantly interchain in nature. By contrast, the triplet EXPA(omega)
      spectrum in the non-luminescent polymer polydiacetylene (PDA) is flat with an
      onset at E=E(g) (~2.25 eV). From this, we infer that intrachain SF that involves
      a triplet-triplet pair state, also known as the 'dark' 2A(g) exciton, dominates
      the triplet photogeneration in PDA polymer as E(g)>2E(T). The intrachain SF
      process was also identified from the MPA(B) response of the triplet PA band in
      PDA. Our work shows that the SF process in pi-conjugated polymers is a much more
      general process than thought previously.

PMID- 25987577
TI  - Kinetics of thermal-assisted delayed fluorescence in blue organic emitters with
      large singlet-triplet energy gap.
AB  - The kinetics of thermally activated delayed fluorescence (TADF) is investigated
      in dilute solutions of organic materials with application in blue light-emitting
      diodes (OLEDs). A method to accurately determine the energy barrier (DeltaE(a))
      and the rate of reverse intersystem crossing (kRisc) in TADF emitters is
      developed, and applied to investigate the triplet-harvesting mechanism in blue
      emitting materials with large singlet-triplet energy gap (DeltaE(ST)). In these
      materials, triplet-triplet annihilation (TTA) is the dominant mechanism for
      triplet harvesting; however, above a threshold temperature TADF is able to
      compete with TTA and give enhanced delayed fluorescence. Evidence is obtained for
      the interplay between the TTA and the TADF mechanisms in these materials.

PMID- 25987578
TI  - Triplet energies and excimer formation in meta- and para-linked carbazolebiphenyl
      matrix materials.
AB  - We present a spectroscopic investigation on the effect of changing the position
      where carbazole is attached to biphenyl in carbazolebiphenyl (CBP) on the triplet
      state energies and the propensity to excimer formation. For this, two CBP
      derivatives have been prepared with the carbazole moieties attached at the (para)
      4- and 4(')-positions (pCBP) and at the (meta) 3- and 3(')-positions (mCBP) of
      the biphenyls. These compounds are compared to analogous mCDBP and pCDBP, i.e.
      two highly twisted carbazoledimethylbiphenyls, which have a high triplet energy
      at about 3.0 eV and tend to form triplet excimers in a neat film. This torsion in
      the structure is associated with localization of the excited state onto the
      carbazole moieties. We find that in mCBP and pCBP, excimer formation is prevented
      by localization of the triplet excited state onto the central moiety. As
      conjugation can continue from the central biphenyls into the nitrogen of the
      carbazole in the para-connected pCBP, emission involves mainly the benzidine. By
      contrast, the meta-linkage in mCBP limits conjugation to the central biphenyl.
      The associated shorter conjugation length is the reason for the higher triplet
      energy of 2.8 eV in mCBP compared with the 2.65 eV in pCBP. 

PMID- 25987580
TI  - Organic semiconductor spintronics: utilizing triplet excitons in organic
      electronics.

PMID- 25987579
TI  - Multiple exciton generation in quantum dots versus singlet fission in molecular
      chromophores for solar photon conversion.
AB  - Both multiple exciton generation (MEG) in semiconductor nanocrystals and singlet
      fission (SF) in molecular chromophores have the potential to greatly increase the
      power conversion efficiency of solar cells for the production of solar
      electricity (photovoltaics) and solar fuels (artificial photosynthesis) when used
      in solar photoconverters. MEG creates two or more excitons per absorbed photon,
      and SF produces two triplet states from a single singlet state. In both cases,
      multiple charge carriers from a single absorbed photon can be extracted from the
      cell and used to create higher power conversion efficiencies for a photovoltaic
      cell or a cell that produces solar fuels, like hydrogen from water splitting or
      reduced carbon fuels from carbon dioxide and water (analogous to biological
      photosynthesis). The similarities and differences in the mechanisms and
      photoconversion cell architectures between MEG and SF are discussed. 

PMID- 25987581
TI  - Quality of life and clinical characteristics in a nonselected sample of patients
      with schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia experience low quality of life (QOL).
      AIMS: To examine QOL in these patients and the relation between QOL and illness
      duration, adjusted daily doses (ADDs) of antipsychotics, body mass index (BMI),
      waist circumference and smoking. METHODS: In this naturalistic, cross-sectional
      study, 82 patients were interviewed about smoking habits. Patients completed a
      QOL questionnaire (World Health Organization Quality of Life-Bref) consisting of
      physical, psychological, social and environmental domains and had height, weight
      and waist circumference measured. The characteristics and QOL were correlated
      using multiple regression analysis. RESULTS: QOL was significantly lower in the
      patients than in the general population (p < .01). In first-ever diagnosed
      patients, QOL was associated with BMI (regression coefficient (RC): physical 
      0.73, psychological -1.44 and environmental -0.55; all p < .05), ADD (RC:
      physical 3.71, psychological 4.37 and environmental 2.94; all p < .10) and
      smoking (RC: physical -0.69; p < .01). In the long-term ill patients, QOL was
      associated with BMI (RC: physical -1.19 and psychological -1.28; all p < .05) and
      illness duration (RC: physical 1.38; p < .05). CONCLUSION: Patients experienced
      low QOL. Lower QOL was associated with high BMI, low ADD and smoking in first
      ever diagnosed patients and with high BMI and short illness duration in long-term
      ill patients.

PMID- 25987582
TI  - Reflexivity: The Creation of Liminal Spaces--Researchers, Participants, and
      Research Encounters.
AB  - Reflexivity is defined as the constant movement between being in the phenomenon
      and stepping outside of it. In this article, we specify three foci of reflexivity
      -the researcher, the participant, and the encounter--for exploring the interview
      process as a dialogic liminal space of mutual reflection between researcher and
      participant. Whereas researchers' reflexivity has been discussed extensively in
      the professional discourse, participants' reflexivity has not received adequate
      scholarly attention, nor has the promise inherent in reflective processes
      occurring within the encounter.

PMID- 25987583
TI  - What Was (Also) at Stake When a Robot Bathtub Was Implemented in a Danish Elder
      Center: A Constructivist Secondary Qualitative Analysis.
AB  - Assistive technologies are often considered to be passive tools implemented in
      targeted processes. Our previous study of the implementation of the robot bathtub
      in a Danish elder center suggested that purposeful rationality was not the only
      issue at stake. To further explore this, we conducted a constructivist secondary
      qualitative analysis. Data included interviews, participant observations, working
      documents, and media coverage. The analysis was carried out in two phases and
      revealed that the bathing of the older people was constructed as a problem that
      could be offensive to the users' integrity, damaging to their well-being, and
      physically strenuous for the staff. The older users and the nursing staff were
      constructed as problem carriers. We conclude that technological solutions are not
      merely neutral and beneficial solutions to existing problems, but are rather part
      of strategic games contributing to the construction of the very problems they
      seek to solve.

PMID- 25987584
TI  - An Ethnographic-Discursive Approach to Parental Self-Help Groups: The Case of
      ADHD.
AB  - Mutual aid groups have become a common form of help in the mental health field.
      Although self-help groups are associated with a range of health and social
      benefits, they remain poorly understood in terms of the dynamics of their
      interactions. Adopting an ethnographic-discursive approach, we conducted a 6
      month observation of the meetings of a self-help group of parents with children
      diagnosed with attention deficit/hyperactivity disorder (ADHD) to analyze the
      discursive dynamics of the interactions that characterized the group. Using a set
      of discursive strategies and practices, the parents promoted a homogeneity of
      viewpoints and experiences within the group and constructed a shared and
      consensual narrative to endorse a specific understanding of ADHD. The production
      of both homogeneity within the group and a shared narrative served to absolve
      parents of guilt, helped parents to signify their experience within a blaming
      social context, and preserved their identities as "good parents."

PMID- 25987585
TI  - Measurement of the weighted peak level for occupational exposure to gradient
      magnetic fields for 1.5 and 3 Tesla MRI body scanners.
AB  - The purpose of this work is to give a contribution to the construction of a
      comprehensive knowledge of the exposure levels to gradient magnetic fields (GMF)
      in terms of the weighed peak (WP), especially for 3 Tesla scanners for which
      there are still few works available in the literature. A new generation probe for
      the measurement of electromagnetic fields in the range of 1 Hz-400 kHz was used
      to assess the occupational exposure levels to the GMF for 1.5 and 3.0 Tesla MRI
      body scanners, using the method of the WP according to the International
      Commission on Non-Ionizing Radiation Protection (ICNIRP) approach. The probe was
      placed at a height of 1.1 m, close to the MRI scanners, where operators could
      stay during some medical procedures with particular issues. The measurements were
      performed for a set of typical acquisition sequences for body (liver) and head
      exams. The measured values of WP were in compliance with ICNIRP 2010 reference
      levels for occupational exposures. 

PMID- 25987586
TI  - The Bacterial Sec Pathway of Protein Export: Screening and Follow-Up.
AB  - Most noncytoplasmic bacterial proteins are exported through the SecYEG channel in
      the cytoplasmic membrane. This channel and its associated proteins, collectively
      referred to as the Sec pathway, have strong appeal as a possible antibiotic drug
      target, yet progress toward new drugs targeting this pathway has been slow,
      perhaps due partly to many researchers' focus on a single component, the SecA
      ATPase. Here we report on a pathway-based screen in which beta-galactosidase
      (beta-gal) activity is trapped in the cytoplasm of Escherichia coli cells if
      translocation through SecYEG is impaired. Several hit compounds passed a
      counterscreen distinguishing between beta-gal overexpression and impaired beta
      gal export. However, the most extensively characterized hit gave limited E. coli
      growth inhibition (EC(50) >= 400 uM), and growth inhibition could not be
      unambiguously linked to the compound's effect on the Sec pathway. Our study and
      others underscore the challenges of finding potent druglike hits against this
      otherwise promising drug target.

PMID- 25987587
TI  - Echolocation in the bat, Rhinolophus capensis: the influence of clutter,
      conspecifics and prey on call design and intensity.
AB  - Echolocating bats are exposed not only to the echoes of their own calls, but
      often the signals of conspecifics and other bats. For species emitting short,
      frequency modulated signals e.g. vespertilionoids, adjustments in both the
      frequency and time domain have been observed in such situations. However, bats
      using long duration, constant frequency calls may confront special challenges,
      since these bats should be less able to avoid temporal and frequency overlap.
      Here we investigated echolocation call design in the highduty cycle bat,
      Rhinolophus capensis, as bats flew with either a conspecific or heterospecific in
      a large outdoor flight-room. We compared these recordings to those made of bats
      flying alone in the same flight-room, and in a smaller flight room, alone, and
      hunting tethered moths. We found no differences in duty cycle or peak frequency
      of the calls of R. capensis across conditions. However, in the presence of a
      conspecific or the vespertilionoid, Miniopterus natalensis, R. capensis produced
      longer frequency-modulated downward sweeps at the terminus of their calls with
      lower minimum frequencies than when flying alone. In the presence of the larger
      high-duty cycle bat, R. clivosus, R. capensis produced shorter calls than when
      flying alone or with a conspecific. These changes are similar to those of
      vespertilionoids when flying from open to more cluttered environments. They are
      not similar to those differences observed in vespertilionoids when flying with
      other bats. Also unlike vespertilinoids, R. capensis used calls 15 dB less
      intense in conspecific pairs than when alone. 

PMID- 25987588
TI  - Accountable Care Organizations: what they mean for the country and for
      neurointerventionalists.
AB  - The Affordable Care Act is celebrating its fifth anniversary and remains one of
      the most significant attempts to reform healthcare in US history. Prior to the
      federal legislation, Accountable Care Organizations had largely been part of an
      academic discussion about how to control rising healthcare costs, but have since
      become a fixture in our national healthcare landscape. A fundamental shift is
      underway in the relationship between healthcare delivery and payment models. Some
      elements of Accountable Care Organizations may remain unfamiliar to most
      healthcare providers, including neurointerventional specialists. In this paper we
      review the fundamental concepts behind and the current forms of Accountable Care
      Organizations, and discuss the challenges and opportunities they present for
      neurointerventionalists. 

PMID- 25987589
TI  - Kissing-Y stenting for endovascular treatment of complex wide necked bifurcation
      aneurysms using Acandis Acclino stents: results and literature review.
AB  - INTRODUCTION: Y-configured stent assisted coiling is a promising therapeutic
      option to ensure safe coil embolization and preserve the affected arteries in
      complex wide necked aneurysms. We present our experience with self-expanding
      Acandis Acclino stents for the treatment of complex aneurysms using the kissing-Y
      technique. METHODS: We retrospectively reviewed seven patients with seven complex
      aneurysms (three anterior communicating artery (AcomA), two middle cerebral
      artery, one basilar artery/superior cerebellar artery, and one vertebral
      artery/posterior inferior cerebellar artery) who were treated with the kissing-Y
      technique by stent assisted coiling from June 2013 to July 2014, with follow-up
      until January 2015. DSA follow-up was up to 17 months, with a mean follow-up
      period of 10 months. Six patients were treated electively and one in the acute
      phase of a subarachnoid hemorrhage. In all cases, closed cell Acandis Acclino
      stents were used. We evaluated procedural complications, clinical outcomes, and
      mid term angiographic follow-up. Additionally, a literature review is provided.
      RESULTS: In all patients, stents were successfully placed and implanted. One
      patient developed a periprocedural thromboembolic complication not directly
      related to the stents. No other periprocedural or postprocedural complications
      were encountered. Follow-up examinations showed stable and total occlusion of all
      coiled aneurysms. CONCLUSIONS: The results of our study show that the kissing-Y
      technique using closed cell Acandis Acclino stents followed by coil embolization
      is a feasible treatment option for selected complex bifurcation aneurysms.

PMID- 25987590
TI  - Flow diversion of large internal carotid artery aneurysms with the surpass
      device: impressions and technical nuance from the initial North American
      experience.
AB  - BACKGROUND: Flow diversion is an important tool for treatment of cerebral
      aneurysms, particularly large and giant aneurysms. The Surpass flow diverter is a
      new system under evaluation in the USA. OBJECTIVE: To report our initial
      experience of 20 cases with the Surpass flow diverter to demonstrate its basic
      properties, the required triaxial delivery platform, and the methodologies used
      to deploy it during treatment of large internal carotid artery (ICA) aneurysms
      METHODS: Twenty patients with ICA aneurysms >=10 mm with >=4 mm neck treated as
      part of the Surpass IntraCranial Aneurysm Embolization System Pivotal Trial (the
      SCENT trial; Stryker) were included. Details of patient demographics, aneurysm
      characteristics, and technical procedures were collected. RESULTS: Twenty
      patients (mean age 63.3+/-1.3 years; range 51-72) with 20 unruptured aneurysms
      (mean size 13.4+/-0.9 mm; range 10-21 mm) were treated. For proximal access, 60%
      of cases had aortic arch >=grade II, 55% had significant cervical ICA tortuosity,
      and 60% had cavernous ICA >=grade II. The Surpass device was implanted in 19/20
      (95%) cases. Of 19 cases, a single device was used in 18 cases (95%) and 2
      devices in only 1 case (5%). Balloon angioplasty was performed in 8/19 cases
      (42%). Complete aneurysm neck coverage and adequate vessel wall apposition was
      obtained in all 19 cases. CONCLUSIONS: Surpass is a next-generation flow diverter
      with unique device-specific and delivery-specific features compared with
      clinically available endoluminal flow diverters. Our initial experience
      demonstrates a favorable technical profile in treatment of large and giant ICA
      aneurysms. TRIAL REGISTRATION NUMBER: NCT01716117.

PMID- 25987591
TI  - SILK flow diverter for complex intracranial aneurysms: a Canadian registry.
AB  - INTRODUCTION: The SILK flow diverter (SFD) is used for the treatment of complex
      intracranial aneurysms. Small case series have been reported in the literature
      but few studies with a large number of patients have been published. We present
      our experience with the SFD for the treatment of intracranial aneurysms in
      Canada. METHODS: Centers across Canada using SFDs were contacted to fill out a
      case report form for patients treated with an SFD in their center. Individual
      centers were responsible for approval from their ethics committee. Image analysis
      was performed by individual operators. The case report forms were collected and
      the final analysis was performed. RESULTS: A total of 92 patients were treated
      with SFDs in eight centers in Canada between January 2009 and August 2013. The
      aneurysms were located in the posterior circulation in 16 patients and in the
      anterior circulation in 76 patients. Most aneurysms (75%) were saccular in shape;
      22% were fusiform and 3% were blister aneurysms. The size of the aneurysms varied
      from 2 to 60 mm with the neck varying from 2 to 60 mm. Perioperative morbidity
      and mortality were 8.7% and 2.2%, respectively. At the last available follow-up,
      83.1% of the aneurysms were either completely or near-completely occluded. The
      rate of complications was higher for fusiform aneurysms (p<0.001). CONCLUSIONS:
      The SFD appears to be an important tool for the treatment of complex intracranial
      aneurysms. Treatment outcomes and complication rates remain a problem, but should
      be considered in the context of available alternative interventions. Ongoing
      analysis of flow-diverting stents for radiographic and clinical performance is
      required.

PMID- 25987593
TI  - Retraction notice.
AB  - At the request of the Editor and the Publisher, the following article has been
      retracted.Imputing a randomly censored covariate in a linear regression model
      published online before print onMay 17, 2015, doi:10.1177/0962280215586011.
      Authored by Emmanuel Sampene & Folefac D Atem
      http://smm.sagepub.com/content/early/2015/05/15/0962280215586011.abstractThe
      above article was published without the full and proper permission from the
      rights holder to publish the data source.

PMID- 25987592
TI  - Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery
      dissection: is early surgical exploration warranted?
AB  - The natural history of spontaneous cerebral artery dissection and thrombosis
      remains uncertain. Concurrent subarachnoid hemorrhage further complicates the
      therapeutic approach. Thus the best strategy for managing patients with acute
      vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we
      present a case of spontaneous posterior inferior cerebellar artery dissection
      presenting with subarachnoid hemorrhage and acute thrombosis. Although the
      patient was initially managed conservatively, angiographic follow-up demonstrated
      recanalization of the diseased vessel, necessitating definitive treatment. Thus
      we propose that angiographic follow-up is necessary in the management of patients
      with subarachnoid hemorrhage in association with apparent vessel thrombosis. 

PMID- 25987594
TI  - Ethical, legal and professional issues arising from social media coverage by UK
      Helicopter Emergency Medical Services.
AB  - OBJECTIVE: Social media (SoMe) are gaining increasing acceptance among, and use
      by, healthcare service deliverers and workers. UK Helicopter Emergency Medical
      Services (HEMS) use SoMe to deliver service information and to fundraise, among
      other purposes. This article examines UK HEMS use of SoMe between January and
      February 2014 to determine the extent of adoption and to highlight trends in use.
      METHODS: The database of the Association of Air Ambulances, crosschecked with UK
      Emergency Aviation, was used to identify flying, charitable UK HEMS. This search
      identified 28 UK HEMS, of which 24 services met the criteria for selection for
      review. Using information harvested from the public domain, we then
      systematically documented SoMe use by the services. RESULTS: SoMe use by UK HEMS
      is extensive but not uniform. All selected UK HEMS maintained websites with
      blogs, as well as Facebook, Twitter, Wikipedia and JustGiving profiles, with the
      majority of services using Ebay for Charity, LinkedIn and YouTube. Some HEMS also
      held a presence on Pinterest, Google+, Instagram and Flickr, with a minority of
      services maintaining their own Rich Site Summary (RSS) feed. CONCLUSIONS: The
      SoMe adopted, while varied, allowed for increased, and different forms of,
      information delivery by HEMS to the public, often in real time. Such use, though,
      risks breaching patient confidentiality and data protection requirements,
      especially when information is viewed cumulatively across platforms. There is an
      urgent need for the continued development of guidance in this unique setting to
      protect patients while UK HEMS promote and fundraise for their charitable
      activities.

PMID- 25987595
TI  - Predicting older adults who return to the hospital or die within 30 days of
      emergency department care using the ISAR tool: subjective versus objective risk
      factors.
AB  - BACKGROUND: We sought to evaluate the ability of the Identification of Seniors At
      Risk (ISAR) tool to differentiate between older adult patients having a poor
      outcome within 30 days of emergency department (ED) care and those who do not. We
      compare prognostic accuracy of subjective versus objective risk factors. METHODS:
      202 community-dwelling patients age 65 years and older presenting to two EDs were
      prospectively enrolled. Participants completed the six-question ISAR and
      objective testing (cognition, ambulation, vision). We reviewed electronic medical
      records for current medications, hospitalisations in the past six months, ED
      disposition, length of hospital stay, subsequent ED visits or inpatient
      admissions or death at 30 days. Participants were given a point for each risk
      factor present; subjective and objective risk factors were scored separately. We
      tested ability of individual risk factors and scores to predict a composite
      outcome of subsequent ED visit, postdischarge hospitalisation or death by day 30
      after the index ED visit. We computed receiver operating curve area under the
      curves (AUC) to determine tool discrimination. RESULTS: 23% of participants had a
      poor 30-day outcome. The optimum subjective ISAR cut-off score for screening was
      >=2, which was present in 84% of participants, had a sensitivity of 91% and
      specificity of 19%. Using the subjective ISAR tool, the AUC was 0.66. The optimum
      objective ISAR-related risk cut-off score for screening was >=3, which was
      present in 82% of participants, had a sensitivity of 87% and specificity of 40%.
      Using the objective ISAR-related tool, the AUC was 0.69. CONCLUSIONS: The self
      reported ISAR tool did not discriminate well between older adults with or without
      30-day hospital revisit or death. An optimum score of >=2 would identify many
      older adults at no apparent increased risk of poor outcomes at 30 days. Using
      objective ISAR-related risk factors did not improve overall discrimination.

PMID- 25987596
TI  - Coagulation assessment with the new generation of oral anticoagulants.
AB  - Long-term oral anticoagulant (OAC) therapy is used for the treatment and
      prevention of thrombosis and thromboembolism. As OAC use is so widespread,
      emergency physicians are likely to encounter patients on anticoagulant therapy in
      the emergency department (ED) on a regular basis, either for the same reasons as
      the population in general or as a result of the increased bleeding risk that OAC
      use entails.The vitamin K antagonist warfarin has been the standard OAC for
      several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban
      and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply 'NOACs')
      have become available for long-term use. Protocols for assessing and managing
      warfarin-treated patients in the ED are well established and include
      international normalised ratio (INR) testing, which helps guide patient
      management. However, the INR does not give an accurate evaluation of coagulation
      status with NOACs, and alternative tests are therefore needed for use in
      emergency settings. This paper discusses what information the INR provides for a
      patient taking warfarin and which coagulation tests can guide the physician when
      treating patients on one of the NOACs, as well as other differences in emergency
      anticoagulation management. 

PMID- 25987603
TI  - The yeast ERAD-C ubiquitin ligase Doa10 recognizes an intramembrane degron.

PMID- 25987597
TI  - Social working memory and its distinctive link to social cognitive ability: an
      fMRI study.
AB  - Engaging social working memory (SWM) during effortful social cognition has been
      associated with neural activation in two neurocognitive systems: the medial
      frontoparietal system and the lateral frontoparietal system. However, the
      respective roles played by these systems in SWM remain unknown. Results from this
      study demonstrate that only the medial frontoparietal system supports the social
      cognitive demands managed in SWM. In contrast, the lateral frontoparietal system
      supports the non-social cognitive demands that are needed for task performance,
      but that are independent of the social cognitive computations. Moreover,
      parametric increases in the medial frontoparietal system, but not the lateral
      frontoparietal system, in response to SWM load predicted performance on a
      challenging measure of perspective-taking. Thus, the medial frontoparietal system
      may uniquely support social cognitive processes in working memory and the working
      memory demands afforded by effortful social cognition, such as the need to track
      another person's perspective in mind. 

PMID- 25987604
TI  - Bub3 promotes Cdc20-dependent activation of the APC/C in S. cerevisiae.
AB  - The spindle checkpoint ensures accurate chromosome segregation by sending a
      signal from an unattached kinetochore to inhibit anaphase onset. Numerous studies
      have described the role of Bub3 in checkpoint activation, but less is known about
      its functions apart from the spindle checkpoint. In this paper, we demonstrate
      that Bub3 has an unexpected role promoting metaphase progression in budding
      yeast. Loss of Bub3 resulted in a metaphase delay that was not a consequence of
      aneuploidy or the activation of a checkpoint. Instead, bub3Delta cells had
      impaired binding of the anaphase-promoting complex/cyclosome (APC/C) with its
      activator Cdc20, and the delay could be rescued by Cdc20 overexpression.
      Kinetochore localization of Bub3 was required for normal mitotic progression, and
      Bub3 and Cdc20 colocalized at the kinetochore. Although Bub1 binds Bub3 at the
      kinetochore, bub1Delta cells did not have compromised APC/C and Cdc20 binding.
      The results demonstrate that Bub3 has a previously unknown function at the
      kinetochore in activating APC/C-Cdc20 for normal mitotic progression. 

PMID- 25987606
TI  - Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and
      ER-vacuole contacts.
AB  - Organelle contact sites perform fundamental functions in cells, including lipid
      and ion homeostasis, membrane dynamics, and signaling. Using a forward proteomics
      approach in yeast, we identified new ER-mitochondria and ER-vacuole contacts
      specified by an uncharacterized protein, Ylr072w. Ylr072w is a conserved protein
      with GRAM and VASt domains that selectively transports sterols and is thus termed
      Ltc1, for Lipid transfer at contact site 1. Ltc1 localized to ER-mitochondria and
      ER-vacuole contacts via the mitochondrial import receptors Tom70/71 and the
      vacuolar protein Vac8, respectively. At mitochondria, Ltc1 was required for cell
      viability in the absence of Mdm34, a subunit of the ER-mitochondria encounter
      structure. At vacuoles, Ltc1 was required for sterol-enriched membrane domain
      formation in response to stress. Increasing the proportion of Ltc1 at vacuoles
      was sufficient to induce sterol-enriched vacuolar domains without stress. Thus,
      our data support a model in which Ltc1 is a sterol-dependent regulator of
      organelle and cellular homeostasis via its dual localization to ER-mitochondria
      and ER-vacuole contact sites. 

PMID- 25987605
TI  - Kinetochore-localized BUB-1/BUB-3 complex promotes anaphase onset in C. elegans.
AB  - The conserved Bub1/Bub3 complex is recruited to the kinetochore region of mitotic
      chromosomes, where it initiates spindle checkpoint signaling and promotes
      chromosome alignment. Here we show that, in contrast to the expectation for a
      checkpoint pathway component, the BUB-1/BUB-3 complex promotes timely anaphase
      onset in Caenorhabditis elegans embryos. This activity of BUB-1/BUB-3 was
      independent of spindle checkpoint signaling but required kinetochore
      localization. BUB-1/BUB-3 inhibition equivalently delayed separase activation and
      other events occurring during mitotic exit. The anaphase promotion function
      required BUB-1's kinase domain, but not its kinase activity, and this function
      was independent of the role of BUB-1/BUB-3 in chromosome alignment. These results
      reveal an unexpected role for the BUB-1/BUB-3 complex in promoting anaphase onset
      that is distinct from its well-studied functions in checkpoint signaling and
      chromosome alignment, and suggest a new mechanism contributing to the
      coordination of the metaphase-to-anaphase transition. 

PMID- 25987607
TI  - The Msd1-Wdr8-Pkl1 complex anchors microtubule minus ends to fission yeast
      spindle pole bodies.
AB  - The minus ends of spindle microtubules are anchored to a microtubule-organizing
      center. The conserved Msd1/SSX2IP proteins are localized to the spindle pole body
      (SPB) and the centrosome in fission yeast and humans, respectively, and play a
      critical role in microtubule anchoring. In this paper, we show that fission yeast
      Msd1 forms a ternary complex with another conserved protein, Wdr8, and the minus
      end-directed Pkl1/kinesin-14. Individual deletion mutants displayed the identical
      spindle-protrusion phenotypes. Msd1 and Wdr8 were delivered by Pkl1 to mitotic
      SPBs, where Pkl1 was tethered through Msd1-Wdr8. The spindle-anchoring defect
      imposed by msd1/wdr8/pkl1 deletions was suppressed by a mutation of the plus end
      directed Cut7/kinesin-5, which was shown to be mutual. Intriguingly, Pkl1 motor
      activity was not required for its anchoring role once targeted to the SPB.
      Therefore, spindle anchoring through Msd1-Wdr8-Pkl1 is crucial for balancing the
      Cut7/kinesin-5-mediated outward force at the SPB. Our analysis provides
      mechanistic insight into the spatiotemporal regulation of two opposing kinesins
      to ensure mitotic spindle bipolarity. 

PMID- 25987608
TI  - Role of stimulated intrarenal angiotensinogen in hypertension.
AB  - Experimental models of hypertension and patients with inappropriately increased
      renin formation due to a stenotic kidney, arteriosclerotic narrowing of the renal
      arterioles or a rare juxtaglomerular cell tumor have shown a progressive
      augmentation of the intrarenal/intratubular renin-angiotensin system (RAS). The
      increased intrarenal angiotensin II (Ang II) elicits renal vasoconstriction and
      enhanced tubular sodium reabsorption in proximal and distal nephron segments. The
      enhanced intrarenal Ang II levels are due to both increased Ang II type 1 (AT1)
      receptor mediated Ang II uptake and AT1 receptor dependent stimulation of renal
      angiotensinogen (AGT) mRNA and augmented AGT production. The increased AGT
      formation and secretion into the proximal tubular lumen leads to local formation
      of Ang II, which stimulates proximal transporters such as the sodium/hydrogen
      exchanger. Enhanced AGT production also leads to spillover of AGT into the distal
      nephron segments as reflected by AGT in the urine, which provides an index of
      intrarenal RAS activity. There is also increased Ang II concentration in distal
      nephron with stimulation of distal sodium transport. Increased urinary excretion
      of AGT has been demonstrated in patients with hypertension, type 1 and type 2
      diabetes mellitus, and several types of chronic kidney diseases indicating an
      upregulation of intrarenal RAS activity. 

PMID- 25987609
TI  - Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New
      Antiseptic.
AB  - Olanexidine gluconate [1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate]
      (development code OPB-2045G) is a new monobiguanide compound with bactericidal
      activity. In this study, we assessed its spectrum of bactericidal activity and
      mechanism of action. The minimal bactericidal concentrations of the compound for
      30-, 60-, and 180-s exposures were determined with the microdilution method using
      a neutralizer against 320 bacterial strains from culture collections and clinical
      isolates. Based on the results, the estimated bactericidal olanexidine
      concentrations with 180-s exposures were 869 MUg/ml for Gram-positive cocci (155
      strains), 109 MUg/ml for Gram-positive bacilli (29 strains), and 434 MUg/ml for
      Gram-negative bacteria (136 strains). Olanexidine was active against a wide range
      of bacteria, especially Gram-positive cocci, including methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant enterococci, and had a spectrum of
      bactericidal activity comparable to that of commercial antiseptics, such as
      chlorhexidine and povidone-iodine. In vitro experiments exploring its mechanism
      of action indicated that olanexidine (i) interacts with the bacterial surface
      molecules, such as lipopolysaccharide and lipoteichoic acid, (ii) disrupts the
      cell membranes of liposomes, which are artificial bacterial membrane models,
      (iii) enhances the membrane permeability of Escherichia coli, (iv) disrupts the
      membrane integrity of S. aureus, and (v) denatures proteins at relatively high
      concentrations (>=160 MUg/ml). These results indicate that olanexidine probably
      binds to the cell membrane, disrupts membrane integrity, and its bacteriostatic
      and bactericidal effects are caused by irreversible leakage of intracellular
      components. At relatively high concentrations, olanexidine aggregates cells by
      denaturing proteins. This mechanism differs slightly from that of a similar
      biguanide compound, chlorhexidine. 

PMID- 25987610
TI  - Retrograde Trafficking Inhibitor of Shiga Toxins Reduces Morbidity and Mortality
      of Mice Infected with Enterohemorrhagic Escherichia coli.
AB  - The most deadly outbreak of Escherichia coli O104:H4 occurred in Europe in 2011.
      Here, we evaluated the effects of the retrograde trafficking inhibitor Retro
      2(cycl) in a murine model of E. coli O104:H4 infection. Systemic treatment with
      Retro-2(cycl) significantly reduced body weight loss and improved clinical scores
      and survival rates for O104:H4-infected mice. The present data established that
      Retro-2(cycl) contributes to the protection of mice against O104:H4 infection and
      may represent a novel approach to limit Shiga toxin-producing Escherichia coli
      (STEC)-induced toxicity. 

PMID- 25987611
TI  - Impact of Ciprofloxacin and Clindamycin Administration on Gram-Negative Bacteria
      Isolated from Healthy Volunteers and Characterization of the Resistance Genes
      They Harbor.
AB  - The aim of this study was to assess the impact of ciprofloxacin, clindamycin, and
      placebo administration on culturable Gram-negative isolates and the antibiotic
      resistance genes they harbor. Saliva and fecal samples were collected from
      healthy human volunteers before and at intervals, up to 1 year after antibiotic
      administration. Samples were plated on selective and nonselective media to
      monitor changes in different colony types or bacterial species. Following
      ciprofloxacin administration, there was a decrease of Escherichia coli in feces
      and after clindamycin administration a decrease of Bacteroides in feces and
      Leptotrichia in saliva, which all returned to pretreatment levels within 1 to 4
      months. Ciprofloxacin administration also resulted in an increase in
      ciprofloxacin-resistant Veillonella in saliva, which persisted for 12 months.
      Additionally, 949 aerobic and anaerobic isolates purified from ciprofloxacin- and
      clindamycin-containing plates were screened for the presence of resistance genes.
      Resistance gene carriage was widespread in isolates from all three treatment
      groups, and no association was observed between genes and antibiotic
      administration. Although the anaerobic component of the microbiota was not a
      major reservoir of aerobe-associated antimicrobial resistance (AMR) genes, we
      detected the sulfonamide resistance gene sul2 in anaerobic isolates. The
      longitudinal nature of the study allowed identification of distinct Escherichia
      coli clones harboring multiple resistance genes, including one carrying an
      extended-spectrum beta-lactamase blaCTX-M group 9 gene, which persisted in the
      gut for up to 4 months. This study provided insight into the effects of
      antibiotic administration on healthy microbiota and the diversity of resistance
      genes harbored therein. 

PMID- 25987612
TI  - Nationwide Surveillance of Azole Resistance in Aspergillus Diseases.
AB  - Aspergillus disease affects a broad patient population, from patients with asthma
      to immunocompromised patients. Azole resistance has been increasingly reported in
      both clinical and environmental Aspergillus strains. The prevalence and clinical
      impact of azole resistance in different patient populations are currently
      unclear. This 1-year prospective multicenter cohort study aimed to provide
      detailed epidemiological data on Aspergillus resistance among patients with
      Aspergillus disease in Belgium. Isolates were prospectively collected in 18
      hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and
      treatment data were collected with a questionnaire. The outcome was evaluated to
      1 year after a patient's inclusion. A total of 220 Aspergillus isolates from 182
      patients were included. The underlying conditions included invasive aspergillosis
      (n = 122 patients), allergic bronchopulmonary aspergillosis (APBA) (n = 39
      patients), chronic pulmonary aspergillosis (n = 10 patients), Aspergillus
      bronchitis (n = 7 patients), and aspergilloma (n = 5 patients). The overall azole
      resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and
      was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis,
      aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive
      aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive
      aspergillosis was 52.5%, while susceptibility testing revealed azole resistance
      in only 2/58 of the deceased patients. The clinical impact of Aspergillus
      fumigatus resistance was limited in our patient population with Aspergillus
      diseases. 

PMID- 25987613
TI  - The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium
      tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence.
AB  - Mycobacterium tuberculosis must sense and adapt to host environmental cues to
      establish and maintain an infection. The two-component regulatory system PhoPR
      plays a central role in sensing and responding to acidic pH within the macrophage
      and is required for M. tuberculosis intracellular replication and growth in vivo.
      Therefore, the isolation of compounds that inhibit PhoPR-dependent adaptation may
      identify new antivirulence therapies to treat tuberculosis. Here, we report that
      the carbonic anhydrase inhibitor ethoxzolamide inhibits the PhoPR regulon and
      reduces pathogen virulence. We show that treatment of M. tuberculosis with
      ethoxzolamide recapitulates phoPR mutant phenotypes, including downregulation of
      the core PhoPR regulon, altered accumulation of virulence-associated lipids, and
      inhibition of Esx-1 protein secretion. Quantitative single-cell imaging of a
      PhoPR-dependent fluorescent reporter strain demonstrates that ethoxzolamide
      inhibits PhoPR-regulated genes in infected macrophages and mouse lungs. Moreover,
      ethoxzolamide reduces M. tuberculosis growth in both macrophages and infected
      mice. Ethoxzolamide inhibits M. tuberculosis carbonic anhydrase activity,
      supporting a previously unrecognized link between carbonic anhydrase activity and
      PhoPR signaling. We propose that ethoxzolamide may be pursued as a new class of
      antivirulence therapy that functions by modulating expression of the PhoPR
      regulon and Esx-1-dependent virulence. 

PMID- 25987615
TI  - blaCTX-M-1/9/1 Hybrid Genes May Have Been Generated from blaCTX-M-15 on an IncI2
      Plasmid.
AB  - Three hybrid CTX-M beta-lactamases, CTX-M-64, CTX-M-123, and CTX-M-132, with N
      and C termini matching CTX-M-1 group enzymes and centers matching CTX-M-9 group
      enzymes, have been identified. The hybrid gene sequences suggested recombination
      between blaCTX-M-15 and blaCTX-M-14, the two most common blaCTX-M variants
      worldwide. However, blaCTX-M-64 and blaCTX-M-123 are found in an ISEcp1-blaCTX-M
      transposition unit with a 45-bp "spacer," rather than the 48 bp usually
      associated with blaCTX-M-15, and 112 bp of IncA/C plasmid backbone. This is
      closer to the context of blaCTX-M-55, which has one nucleotide difference from
      blaCTX-M-15, on IncI2 plasmid pHN1122-1. Here, we characterized an IncI2 plasmid
      carrying blaCTX-M-15 with a 45-bp spacer (pHNY2-1) by complete sequencing and
      also sequenced IncI2 plasmids carrying blaCTX-M-64 (pHNAH46-1) or blaCTX-M-132
      (pHNLDH19) and an IncI1 plasmid carrying blaCTX-M-123 (pHNAH4-1). pHNY2-1 has the
      same ISEcp1-blaCTX-M-IncA/C insertion as pHN1122-1, pHNAH46-1, and pHNLDH19, and
      all four plasmid backbones are almost identical. pHNAH4-1 (IncI1 sequence type
      108 [ST108]) carries a transposition unit that includes a 2,720-bp fragment of
      the IncI2 backbone, suggesting ISEcp1-mediated transfer of blaCTX-M-IncA/C-IncI2
      to an IncI1 plasmid. All three hybrid blaCTX-M genes may have resulted from
      recombination between blaCTX-M-14 and blaCTX-M-15 with a 45-bp spacer on an IncI2
      plasmid. Five additional Escherichia coli isolates of different sequence types
      from different provinces, farms, and/or animals had blaCTX-M-64 on a pHNAH46-1
      like IncI2 plasmid and 9 had blaCTX-M-123 on a pHNAH4-1-like IncI1 ST108 plasmid.
      Thus, epidemic IncI plasmids may be responsible for the spread of blaCTX-M-64 and
      blaCTX-M-123 between different animals and different locations in China. 

PMID- 25987614
TI  - Causes and Implications of the Disappearance of Rifampin Resistance in a Rat
      Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis.
AB  - Orthopedic foreign body-associated infections are often treated with rifampin
      based combination antimicrobial therapy. We previously observed that rifampin
      resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolates were
      present 2 days after cessation of rifampin therapy in experimental foreign body
      osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14
      days after the completion of treatment. We studied two rifampin-resistant
      isolates recovered 2 days after treatment and one rifampin-susceptible isolate
      recovered 14 days after treatment. Growing these isolates alone in vitro or in
      vivo demonstrated no fitness defects; however, in mixed culture, rifampin
      susceptible bacteria outcompeted rifampin-resistant bacteria. In vivo, two
      courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days)
      yielded a greater decrease in bacterial quantity in the bones of treated animals
      14 days following treatment than that in animals receiving a single course of
      treatment (P = 0.0398). In infections established with equal numbers of rifampin
      resistant and rifampin-susceptible bacteria, one course of rifampin treatment did
      not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible
      isolates were recovered both 2 days and 14 days following treatment completion;
      however, the proportion of animals with rifampin-resistant isolates was lower at
      14 days than that at 2 days following treatment completion (P = 0.024). In
      untreated animals infected with equal numbers of rifampin-resistant and rifampin
      susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively
      recovered, indicating the outcompetition of rifampin-resistant by rifampin
      susceptible isolates. The data presented imply that although there is no apparent
      fitness defect in rifampin-resistant bacteria when grown alone, they are
      outcompeted by rifampin-susceptible bacteria when the two are present together.
      The findings also suggest that selected rifampin resistance may not persist in
      initially rifampin-susceptible infections following the discontinuation of
      rifampin. 

PMID- 25987616
TI  - The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from
      Mycobacterium tuberculosis.
AB  - 8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit
      decaprenylphosphoryl-beta-d-ribose 2'-oxidase (DprE1) and display nanomolar
      bactericidal activity against Mycobacterium tuberculosis in vitro. Structure
      activity relationship (SAR) studies revealed the 8-nitro group of the BTZ
      scaffold to be crucial for the mechanism of action, which involves formation of a
      semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution
      of the 8-nitro group has led to extensive loss of antimycobacterial activity.
      Here, we report the synthesis and characterization of the pyrrole
      benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain
      significant antimycobacterial activity, with MICs of 0.16 MUg/ml against M.
      tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration
      (IC50) values of <8 MUM and present favorable in vitro absorption-distribution
      metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The
      most promising compound, PyrBTZ01, did not show efficacy in a mouse model of
      acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition
      requires a combination of both covalent bond formation and compound potency. 

PMID- 25987617
TI  - Identification of New Natural CphA Metallo-beta-Lactamases CphA4 and CphA5 in
      Aeromonas veronii and Aeromonas hydrophila Isolates from Municipal Sewage in
      Central Italy.
AB  - Two new natural CphA metallo-beta-lactamases, the CphA4 and CphA5 enzymes, were
      identified in water samples from municipal sewage in central Italy. Compared to
      CphA, the CphA4 and CphA5 enzymes showed numerous point mutations. These enzymes
      have a narrow spectrum of substrates focused on carbapenems only. CphA5 showed
      kcat values about 40-, 12-, and 97-fold higher than those observed for CphA4
      versus imipenem, ertapenem, and biapenem, respectively. 

PMID- 25987618
TI  - Combinations of beta-Lactam Antibiotics Currently in Clinical Trials Are
      Efficacious in a DHP-I-Deficient Mouse Model of Tuberculosis Infection.
AB  - We report here a dehydropeptidase-deficient murine model of tuberculosis (TB)
      infection that is able to partially uncover the efficacy of marketed broad
      spectrum beta-lactam antibiotics alone and in combination. Reductions of up to 2
      log CFU in the lungs of TB-infected mice after 8 days of treatment compared to
      untreated controls were obtained at blood drug concentrations and time above the
      MIC (T>MIC) below clinically achievable levels in humans. These findings provide
      evidence supporting the potential of beta-lactams as safe and mycobactericidal
      components of new combination regimens against TB with or without resistance to
      currently used drugs. 

PMID- 25987619
TI  - Clonal Dissemination of OXA-370-Producing Klebsiella pneumoniae in Rio de
      Janeiro, Brazil.
AB  - Enzymes of the OXA-48 family have become some of the most important beta
      lactamases in the world. A new OXA-48 variant (OXA-370) was first described for
      an Enterobacter hormaechei strain isolated in Rio Grande do Sul (southern region
      of Brazil) in 2013. Here we report detection of the blaOXA-370 gene in 24
      isolates belonging to three Enterobacteriaceae species (22 Klebsiella pneumoniae
      isolates, 1 Enterobacter cloacae isolate, and 1 Enterobacter aerogenes isolate)
      collected from five hospitals in Rio de Janeiro, Brazil, in 2013 and 2014. The
      isolates showed a multidrug resistance profile, and 12.5% were resistant to
      polymyxin B. Besides blaOXA-370, no other carbapenemase genes were observed by
      PCR, whereas blaOXA-1 was found in all isolates and 22 isolates (91.6%) possessed
      blaCTX-M-15. Molecular typing of the K. pneumoniae isolates by pulsed-field gel
      electrophoresis (PFGE) showed the presence of two clonal groups, i.e., KpA (21
      isolates) and KpB (1 isolate). KpA was characterized as sequence type 16 (ST16)
      and KpB as ST1041 by multilocus sequence typing (MLST). ST16 has been observed
      for KPC-producing K. pneumoniae in Rio de Janeiro. Plasmid analysis performed
      with six representative OXA-370-producing isolates showed plasmids harboring the
      blaOXA-370 gene in all strains, ranging from 25 kb to 150 kb. This study suggests
      that there is an urgent need to investigate the presence of OXA-370 and
      dissemination of the K. pneumoniae ST16 clone carrying this gene in Brazil. 

PMID- 25987620
TI  - Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple
      Administrations in Healthy Volunteers.
AB  - Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would
      allow for optimal individualized dosage adjustments and improve drug safety and
      therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of
      clinically relevant, multidrug treatment regimens and to improve the feasibility
      of TDM, we conducted an open-label, multiple-dosing study with 16 healthy
      subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic
      acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide
      (1,500 mg) once daily were administered to both groups. Additionally,
      levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to
      group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were
      administered to group 2. Blood samples for PK analysis were collected up to 24 h
      following the 5 days of drug administration. The PK parameters, including the
      maximum plasma concentration (Cmax) and the area under the plasma concentration
      time curve during a dosing interval at steady state (AUCtau), were evaluated. The
      correlations between the PK parameters and the concentrations at each time point
      were analyzed. The mean Cmax and AUCtau, respectively, for each drug were as
      follows: cycloserine, 24.9 mg/liter and 242.3 mg . h/liter; PAS, 65.9 mg/liter
      and 326.5 mg . h/liter; prothionamide, 5.3 mg/liter and 22.1 mg . h/liter;
      levofloxacin, 6.6 mg/liter and 64.4 mg . h/liter; moxifloxacin, 4.7 mg/liter and
      54.2 mg . h/liter; streptomycin, 42.0 mg/liter and 196.7 mg . h/liter; kanamycin,
      34.5 mg/liter and 153.5 mg . h/liter. The results indicated that sampling at 1,
      2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered
      concomitantly. This study indicates that PK characteristics must be considered
      when prescribing optimal treatments for patients. (This study has been registered
      at ClinicalTrials.gov under registration no. NCT02128308.). 

PMID- 25987621
TI  - Intensity and Mechanisms of Fluoroquinolone Resistance within the H30 and H30Rx
      Subclones of Escherichia coli Sequence Type 131 Compared with Other
      Fluoroquinolone-Resistant E. coli.
AB  - The recent expansion of the H30 subclone of Escherichia coli sequence type 131
      (ST131) and its CTX-M-15-associated H30Rx subset remains unexplained. Although
      ST131 H30 typically exhibits fluoroquinolone resistance, so do multiple other E.
      coli lineages that have not expanded similarly. To determine whether H30 isolates
      have more intense fluoroquinolone resistance than other fluoroquinolone-resistant
      E. coli isolates and to identify possible mechanisms, we determined the MICs for
      four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and
      norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone
      resistant E. coli isolates (48 non-H30 and 41 H30 [23 H30Rx and 18 H30 non-Rx]).
      We compared the MICs with the H30 and H30Rx status, the presence/number of
      nonsynonymous mutations in gyrA, parC, and parE, the presence of aac(6')-1b-cr
      (an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump
      activity (measured as organic solvent tolerance [OST]). Among 1,518 recent E.
      coli clinical isolates, ST131 H30 predominated clonally, both overall and among
      the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared
      with non-H30 isolates, H30 isolates exhibited categorically higher MICs for all
      four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs,
      more nonsynonymous mutations in gyrA, parC, and parE (specifically gyrA D87N,
      parC E84V, and parE I529L), and a numerically higher prevalence of (H30Rx
      associated) aac(6')-1b-cr but lower OST scores. All putative resistance
      mechanisms were significantly associated with the MICs [for aac(6')-1b-cr:
      ciprofloxacin and norfloxacin only]. parC D87N corresponded with ST131 H30 and
      parE I529L with ST131 generally. Thus, more intense fluoroquinolone resistance
      may provide ST131 H30, especially H30Rx [if aac(6')-1b-cr positive], with subtle
      fitness advantages over other fluoroquinolone-resistant E. coli strains. This
      urges both parsimonious fluoroquinolone use and a search for other fitness
      enhancing traits within ST131 H30. 

PMID- 25987622
TI  - Response to Switch from Intermittent Therapy to Daily Therapy for Refractory
      Nodular Bronchiectatic Mycobacterium avium Complex Lung Disease.
AB  - Intermittent three-times-weekly antibiotic therapy is recommended for the initial
      treatment of patients with noncavitary nodular bronchiectatic Mycobacterium avium
      complex lung disease. Although some experts recommend switching from intermittent
      to daily therapy for patients whose sputum has persistent positive cultures after
      intermittent therapy, the clinical efficacy of these modifications is unknown. Of
      20 patients whose sputum had persistent positive cultures after 12 months of
      intermittent antibiotic therapy, specimens from 6 patients (30%) achieved a
      negative culture after a change to daily therapy. 

PMID- 25987623
TI  - Evaluation of Ceftaroline Alone and in Combination against Biofilm-Producing
      Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to
      Daptomycin and Vancomycin in an In Vitro Pharmacokinetic/Pharmacodynamic Model.
AB  - Annually, medical device infections are associated with >250,000 catheter
      associated bloodstream infections (CLABSI), with up to 25% mortality.
      Staphylococcus aureus, a primary pathogen in these infections, is capable of
      biofilm production, allowing organism persistence in harsh environments, offering
      antimicrobial protection. With increases in S. aureus isolates with reduced
      susceptibility to current agents, ceftaroline (CPT) offers a therapeutic
      alternative. Therefore, we evaluated whether CPT would have a role against
      biofilm-producing methicillin-resistant S. aureus (MRSA), including those with
      decreased susceptibilities to alternative agents. In this study, we investigated
      CPT activity alone or combined with daptomycin (DAP) or rifampin (RIF) against 3
      clinical biofilm-producing MRSA strains in an in vitro biofilm
      pharmacokinetic/pharmacodynamic (PK/PD) model. Simulated antimicrobial regimens
      were as follows: 600 mg of CPT every 8 h (q8h) (free maximum concentration of
      drug [fCmax], 17.04 mg/liter; elimination half-life [t1/2], 2.66 h), 12 mg/kg of
      body weight/day of DAP (fCmax, 14.7 mg/liter; t1/2, 8 h), and 450 mg of RIF q12h
      (fCmax, 3.5 mg/liter; t1/2, 3.4 h), CPT plus DAP, and CPT plus RIF. Samples were
      obtained and plated to determine colony counts. Differences in log10 CFU/cm(2)
      were evaluated by analysis of variance with Tukey's post hoc test. The strains
      were CPT and vancomycin susceptible and DAP nonsusceptible (DNS). CPT displayed
      activity throughout the experiment. DAP demonstrated initial activity with
      regrowth at 24 h in all strains. RIF was comparable to the drug-free control, and
      little benefit was observed when combined with CPT. CPT plus DAP displayed potent
      activity, with an average log10 CFU/cm(2) reduction of 3.33 +/- 1.01 from
      baseline. CPT demonstrated activity against biofilm-producing DNS MRSA. CPT plus
      DAP displayed therapeutic enhancement over monotherapy, providing a potential
      option for difficult-to-treat medical device infections. 

PMID- 25987624
TI  - Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones
      against Mycobacterium tuberculosis.
AB  - Clofazimine (CZM) is an antileprosy drug that was recently repurposed for
      treatment of multidrug-resistant tuberculosis. In Mycobacterium tuberculosis, CZM
      appears to act as a prodrug, which is reduced by NADH dehydrogenase (NDH-2), to
      release reactive oxygen species upon reoxidation by O2. CZM presumably competes
      with menaquinone (MK-4), a key cofactor in the mycobacterial electron transfer
      chain, for its reduction by NDH-2. We studied the effect of MK-4 supplementation
      on the activity of CZM against M. tuberculosis and found direct competition
      between CZM and MK-4 for the cidal effect of CZM, against nonreplicating and
      actively growing bacteria, as MK-4 supplementation blocked the drug's activity
      against nonreplicating bacteria. We demonstrated that CZM, like bedaquiline, is
      synergistic in vitro with benzothiazinones such as 2-piperazino-benzothiazinone
      169 (PBTZ169), and this synergy also occurs against nonreplicating bacteria. The
      synergy between CZM and PBTZ169 was lost in an MK-4-rich medium, indicating that
      MK-4 is the probable link between their activities. The efficacy of the dual
      combination of CZM and PBTZ169 was tested in vivo, where a great reduction in
      bacterial load was obtained in a murine model of chronic tuberculosis. Taken
      together, these data confirm the potential of CZM in association with PBTZ169 as
      the basis for a new regimen against drug-resistant strains of M. tuberculosis. 

PMID- 25987625
TI  - Gametocyte Clearance Kinetics Determined by Quantitative Magnetic Fractionation
      in Melanesian Children with Uncomplicated Malaria Treated with Artemisinin
      Combination Therapy.
AB  - Quantitative magnetic fractionation and a published mathematical model were used
      to characterize between-treatment differences in gametocyte density and
      prevalence in 70 Papua New Guinean children with uncomplicated Plasmodium
      falciparum and/or Plasmodium vivax malaria randomized to one of two artemisinin
      combination therapies (artemether-lumefantrine or artemisinin-naphthoquine) in an
      intervention trial. There was an initial rise in peripheral P. falciparum
      gametocyte density with both treatments, but it was more pronounced in the
      artemisinin-naphthoquine group. Model-derived estimates of the median
      pretreatment sequestered gametocyte population were 21/MUl for artemether
      lumefantrine and 61/MUl for artemisinin-naphthoquine (P < 0.001). The median time
      for P. falciparum gametocyte density to fall to <2.5/MUl (below which
      transmission becomes unlikely) was 16 days in the artemether-lumefantrine group
      and 20 days in artemisinin-naphthoquine group (P < 0.001). Gametocyte prevalence
      modeling suggested that artemisinin-naphthoquine-treated children became
      gametocytemic faster (median, 2.2 days) than artemether-lumefantrine-treated
      children (median, 5.3 days; P < 0.001) and had a longer median P. falciparum
      gametocyte carriage time per individual (20 versus 13 days; P < 0.001). Clearance
      of P. vivax gametocytes was rapid (within 3 days) in both groups; however,
      consistent with the reappearance of asexual forms in the main trial, nearly 40%
      of children in the artemether-lumefantrine group developed P. vivax gametocytemia
      between days 28 and 42 compared with 3% of children in the artemisinin
      naphthoquine group. These data suggest that artemisinin is less active than
      artemether against sequestered gametocytes. Greater initial gametocyte release
      after artemisinin-naphthoquine increases the period of potential P. falciparum
      transmission by 4 days relative to artemether-lumefantrine, but the longer
      elimination half-life of naphthoquine than of lumefantrine suppresses P. vivax
      recurrence and consequent gametocytemia. 

PMID- 25987627
TI  - Effect of Variants of Penicillin-Binding Protein 2 on Cephalosporin and
      Carbapenem Susceptibilities in Neisseria gonorrhoeae.
AB  - To characterize the relationship between penicillin-binding protein 2 (PBP2/penA)
      and susceptibility to extended-spectrum cephalosporins (ESCs) and carbapenem
      antibiotics, we compared 17 PBP2 variants in Neisseria gonorrhoeae. Nonmosaic and
      mosaic variants of PBP2 caused decreased susceptibility to ESCs and, to a lesser
      extent, to carbapenems. An A501P substitution in mosaic XXXIV_A501P conferred
      decreased susceptibility to ESCs but restored carbapenem susceptibility to wild
      type levels. These results could aid the molecular surveillance of antimicrobial
      resistance to these agents. 

PMID- 25987626
TI  - Risk Factors for Acquisition and Loss of Clostridium difficile Colonization in
      Hospitalized Patients.
AB  - Asymptomatic colonization may contribute to Clostridium difficile transmission.
      Few data identify which patients are at risk for colonization. We performed a
      prospective cohort study of C. difficile colonization and risk factors for C.
      difficile acquisition and loss in hospitalized patients. Patients admitted to
      medical or surgical wards at a tertiary care hospital were enrolled; interviews
      and chart review were performed to determine patient demographics, C. difficile
      infection (CDI) history, medications, and health care exposures. Stool
      samples/rectal swabs were collected at enrollment and discharge; stool samples
      from clinical laboratory tests were also included. Samples were cultured for C.
      difficile, and the isolates were tested for toxins A and B and ribotyped. Chi
      square tests and univariate logistic regression were used for the analyses. Two
      hundred thirty-five patients were enrolled. Of the patients, 21% were colonized
      with C. difficile (toxigenic and nontoxigenic) at admission and 24% at discharge.
      Ribotype 027 accounted for 6% of the strains at admission and 12% at discharge.
      Of the patients colonized at admission, 78% were also colonized at discharge.
      Cephalosporin use was associated with C. difficile acquisition (47% of patients
      who acquired C. difficile versus 25% of patients who did not; P = 0.03). beta
      lactam-beta-lactamase inhibitor combinations were associated with a loss of C.
      difficile colonization (36% of patients who lost C. difficile colonization versus
      8% of patients colonized at both admission and discharge; P = 0.04), as was
      metronidazole (27% versus 3%; P = 0.03). Antibiotic use affects the epidemiology
      of asymptomatic C. difficile colonization, including acquisition and loss, and it
      requires additional study. 

PMID- 25987629
TI  - MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a
      Staphylococcus aureus Immunocompromised Pneumonia Model.
AB  - Immunocompromised individuals are at increased risk of Staphylococcus aureus
      pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb)
      MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of
      the MAb in immunocompromised mice have not been reported. In this study, passive
      immunization with MEDI4893* increased survival rates and reduced bacterial
      numbers in the lungs in an immunocompromised murine S. aureus pneumonia model.
      Lungs from infected mice exhibited alveolar epithelial damage, protein leakage,
      and bacterial overgrowth, whereas lungs from mice passively immunized with
      MEDI4893* retained a healthy architecture, with an intact epithelial barrier.
      Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined
      with subtherapeutic doses of vancomycin or linezolid improved survival rates,
      compared with the monotherapies. Furthermore, coadministration of MEDI4893* with
      vancomycin or linezolid extended the antibiotic treatment window. These data
      suggest that MAb-mediated neutralization of AT holds promise in strategies for
      prevention and adjunctive therapy among immunocompromised patients. 

PMID- 25987628
TI  - Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in
      Acute Bacterial Skin and Skin Structure Infection.
AB  - A systematic literature review and meta-analysis were conducted to estimate the
      antibacterial treatment effect for linezolid and ceftaroline to inform on the
      design of acute bacterial skin and skin structure infection (ABSSSI)
      noninferiority trials. The primary endpoints included an early clinical treatment
      response (ECTR) defined as cessation of lesion spread at 48 to 72 h
      postrandomization and the test-of-cure (TOC) response defined as total resolution
      of the infection at 7 to 14 days posttreatment. The systematic review identified
      no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in
      uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12
      linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for
      nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95%
      confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0%
      (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for
      nonantibacterial treatment. The early clinical treatment effect could not be
      estimated, given no available placebo or proxy for placebo data for this
      endpoint. Clinical, methodological, and statistical heterogeneity influenced the
      selection of trials for the meta-analysis of the TOC treatment effect estimation.
      The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to
      55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid,
      and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment
      effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The
      antibacterial treatment effect estimation at TOC will inform on the design and
      analysis of future noninferiority ABSSSI clinical trials. 

PMID- 25987630
TI  - Effect of Resistance Mechanisms on the Inoculum Effect of Carbapenem in
      Klebsiella pneumoniae Isolates with Borderline Carbapenem Resistance.
AB  - We aimed to examine the effects of resistance mechanisms on several resistance
      phenotypes among carbapenem-resistant Klebsiella pneumoniae isolates with
      borderline carbapenem MICs. We compared carbapenemase-negative K. pneumoniae with
      carbapenemase-producing K. pneumoniae (CPKP) isolates with similar MICs. CPKP
      isolates exhibited a marked inoculum effect and were more resistant to the
      bactericidal effect of meropenem. This suggests that MIC measurements alone may
      not be sufficient in predicting the therapeutic efficacy of carbapenems against
      CPKP. 

PMID- 25987631
TI  - A Derivative of the Thiopeptide GE2270A Highly Selective against
      Propionibacterium acnes.
AB  - A chemical derivative of the thiopeptide GE2270A, designated NAI003, was found to
      possess a substantially reduced antibacterial spectrum in comparison to the
      parent compound, being active against just a few Gram-positive bacteria. In
      particular, NAI003 retained low MICs against all tested isolates of
      Propionibacterium acnes and, to a lesser extent, against Enterococcus faecalis.
      Furthermore, NAI003 showed a time- and dose-dependent killing of both a
      clindamycin-resistant and a clindamycin-sensitive P. acnes isolate. Gel shift
      experiments indicated that, like the parent compound, NAI003 retained the ability
      to bind to elongation factors Tu (EF-Tus) derived from Escherichia coli, E.
      faecalis, or P. acnes, albeit with reduced efficiency. In contrast, EF-Tus
      derived from the NAI003-insensitive Staphylococcus aureus or Streptococcus
      pyogenes did not bind this compound. These results were confirmed by in vitro
      studies using a hybrid translation system, which indicated that NAI003 can
      inhibit most efficiently protein synthesis driven by the P. acnes EF-Tu. P. acnes
      mutants resistant to NAI003 were isolated by direct plating. With one exception,
      all analyzed strains carried mutations in the tuf gene, encoding EF-Tu. Because
      of its selective effect on P. acnes in comparison to resident skin flora, NAI003
      represents a promising candidate for the topical treatment of acne, which has
      already completed a phase 1 clinical study. 

PMID- 25987632
TI  - Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared
      to Suspension Formulation in Hematological Malignancies.
AB  - Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in
      high-risk patients, is commercially available orally as a suspension formulation
      (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum
      steady-state concentrations (Css) of PCZ stratified by the administered
      formulation for antifungal prophylaxis in patients with myeloid malignancies (n =
      150). The primary outcome was the attainment rate of the target Css of >=700
      ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and
      corrected QT [QTc] interval prolongation) and breakthrough fungal infections.
      Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css
      assessment after at least 7 days of therapy were eligible. The median Css in the
      PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared
      to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab
      group (P < 0.0001). The percentages of patients achieving the target goal of
      >=700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade
      2 or higher) occurred in 1 patient in each group. QTc interval measurements were
      available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ
      tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3)
      and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the
      PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P =
      0.68). We conclude that the use of PCZ-tab was associated with higher Css and
      with the probability of achieving therapeutic goals without worsening of adverse
      effects. 

PMID- 25987633
TI  - In Vitro Antimicrobial Susceptibility Patterns of Blastocystis.
AB  - Blastocystis is the most common human enteric protist with controversial clinical
      significance. Metronidazole is considered a first-line treatment for Blastocystis
      infection; however, there has been increasing evidence for the lack of efficacy
      of this treatment. Treatment failure has been reported in several clinical cases,
      and recent in vitro studies have suggested the occurrence of metronidazole
      resistant strains. In this study, we tested 12 Blastocystis isolates from 4
      common Blastocystis subtypes (ST1, ST3, ST4, and ST8) against 12 commonly used
      antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin,
      trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole,
      fluconazole, nystatin, and itraconazole) at 10 different concentrations in vitro.
      It was found that each subtype showed little sensitivity to the commonly used
      metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and
      secnidazole). This study highlights the efficacy of other potential drug
      treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests
      that current treatment regimens be revised. 

PMID- 25987634
TI  - First Staphylococcal Cassette Chromosome mec Containing a mecB-Carrying Gene
      Complex Independent of Transposon Tn6045 in a Macrococcus caseolyticus Isolate
      from a Canine Infection.
AB  - A methicillin-resistant mecB-positive Macrococcus caseolyticus (strain KM45013)
      was isolated from the nares of a dog with rhinitis. It contained a novel 39-kb
      transposon-defective complete mecB-carrying staphylococcal cassette chromosome
      mec element (SCCmecKM45013). SCCmecKM45013 contained 49 coding sequences (CDSs),
      was integrated at the 3' end of the chromosomal orfX gene, and was delimited at
      both ends by imperfect direct repeats functioning as integration site sequences
      (ISSs). SCCmecKM45013 presented two discontinuous regions of homology (SCCmec
      coverage of 35%) to the chromosomal and transposon Tn6045-associated SCCmec-like
      element of M. caseolyticus JCSC7096: (i) the mec gene complex (98.8% identity)
      and (ii) the ccr-carrying segment (91.8% identity). The mec gene complex, located
      at the right junction of the cassette, also carried the beta-lactamase gene blaZm
      (mecRm-mecIm-mecB-blaZm). SCCmecKM45013 contained two cassette chromosome
      recombinase genes, ccrAm2 and ccrBm2, which shared 94.3% and 96.6% DNA identity
      with those of the SCCmec-like element of JCSC7096 but shared less than 52% DNA
      identity with the staphylococcal ccrAB and ccrC genes. Three distinct
      extrachromosomal circularized elements (the entire SCCmecKM45013,
      PsiSCCmecKM45013 lacking the ccr genes, and SCCKM45013 lacking mecB) flanked by
      one ISS copy, as well as the chromosomal regions remaining after excision, were
      detected. An unconventional circularized structure carrying the mecB gene complex
      was associated with two extensive direct repeat regions, which enclosed two open
      reading frames (ORFs) (ORF46 and ORF51) flanking the chromosomal mecB-carrying
      gene complex. This study revealed M. caseolyticus as a potential disease
      associated bacterium in dogs and also unveiled an SCCmec element carrying mecB
      not associated with Tn6045 in the genus Macrococcus. 

PMID- 25987635
TI  - In Vitro Activity of Ceftolozane Alone and in Combination with Tazobactam against
      Extended-Spectrum-beta-Lactamase-Harboring Enterobacteriaceae.
AB  - Ceftolozane, formally CXA-101, is a new antipseudomonal cephalosporin that is
      also active in vitro against Enterobacteriaceae but is vulnerable to extended
      spectrum beta-lactamases (ESBLs). The addition of tazobactam is intended to
      broaden coverage to most ESBL-producing Escherichia coli and Klebsiella pneumonia
      as well as other Enterobacteriaceae. The in vitro activities of ceftolozane
      tazobactam combinations against 67 clinically and molecularly characterized ESBL
      producing isolates were examined by checkerboard MIC testing to evaluate their
      potential clinical feasibility and to assess the optimal tazobactam
      concentrations to be used in MIC determinations of ceftolozane. Isolates included
      those from E. coli (n = 32), K. pneumoniae (n = 19), Enterobacter cloacae (n =
      15), and Citrobacter freundii (n = 1). Checkerboard experiments were performed to
      study interactions over the range of 0.008 to 64 mg/liter ceftolozane and 0.063
      to 32 mg/liter tazobactam using 2-fold-dilution series. The MIC50 and MIC90 of
      ceftolozane alone for all isolates were 16 and >=64 mg/liter, respectively.
      Increasing concentrations of tazobactam resulted in decreasing MICs of
      ceftolozane. The 50th and 90th percentile concentrations of tazobactam required
      to reduce the MIC of ceftolozane to 8 mg/liter for all organisms in this ESBL
      collection were 0.5 and 4 mg/liter, respectively. For E. coli, K. pneumoniae, and
      E. cloacae, these values were 0.5 and 2, 1 and 16, and 0.5 and 4 mg/liter,
      respectively. When combined with a fixed amount of 4 mg/liter tazobactam (current
      CLSI concentration used for susceptibility testing), 90% of the isolates would
      have an MIC of <=4 mg/liter. The combination ceftolozane-tazobactam is a
      promising alternative option for treating infections due to ESBL-harboring
      isolates. 

PMID- 25987636
TI  - In Vitro Activity of Dalbavancin against Drug-Resistant Staphylococcus aureus
      Isolates from a Global Surveillance Program.
AB  - In over a decade (2002 to 2012) of Staphylococcus aureus surveillance testing on
      62,195 isolates, dalbavancin was demonstrated to be active against isolates that
      were either susceptible or nonsusceptible to daptomycin, linezolid, or
      tigecycline. Nearly all (99.8%) multidrug-resistant methicillin-resistant S.
      aureus isolates were inhibited by dalbavancin at <=0.12 MUg/ml (MIC50/90,
      0.06/0.06 MUg/ml), the current U.S. Food and Drug Administration (U.S. FDA)
      breakpoint. Overall, only 0.35% of the monitored S. aureus isolates had a
      dalbavancin MIC of either 0.25 or 0.5 MUg/ml (i.e., were nonsusceptible). 

PMID- 25987637
TI  - Transfer of CMY-2 Cephalosporinase from Escherichia coli to Virulent Klebsiella
      pneumoniae Causing a Recurrent Liver Abscess.
AB  - A CMY-2-producing capsular type K2 Klebsiella pneumoniae strain (TVGHKP93) with
      multidrug resistance was isolated from a recurrent liver abscess in a patient who
      also carried a CMY-2-producing Escherichia coli strain (TVGHEC01) in the stool.
      TVGHKP93 retained its high virulence compared with that of the isogenic strain
      (TVGHKP60) with wild-type resistance from the first liver abscess. Our
      conjugation experiment showed the successful transfer of the blaCMY-2-carrying
      plasmid from TVGHEC01 into TVGHKP60. The transconjugant showed both high
      virulence and the multidrug-resistant phenotype, as did TVGHKP93. 

PMID- 25987638
TI  - Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal
      Microbiota.
AB  - Ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a
      novel non-beta-lactam beta-lactamase inhibitor, avibactam. The purpose of the
      present study was to investigate the effect of ceftaroline-avibactam on the human
      intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam
      (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8
      h on days 1 to 6 and as a single dose on day 7. Fecal samples were collected on
      day -1 (within 24 h of the first infusion on day 1) and on days 2, 5, 7, 9, 14,
      and 21. Escherichia coli numbers decreased during the study and normalized on day
      21. An increased number of Klebsiella bacteria appeared on day 14 and normalized
      on day 21. The number of other enterobacteria decreased during the study, and the
      number of enterococci decreased from days 2 to 7 and normalized on day 9. Candida
      numbers increased from days 5 to 9 and normalized after day 14. The number of
      lactobacilli decreased during the study and recovered on day 14. The number of
      bifidobacteria decreased on day 2 and normalized on day 21. The number of
      Bacteroides bacteria was unchanged. Clostridium difficile numbers decreased on
      days 7 and 9 and increased on days 14 and 21. A toxigenic C. difficile strain was
      detected in one volunteer on day 21 with no reported adverse events. Plasma
      samples were collected on days -1, 2, 5, and 7. Ceftaroline and avibactam
      concentrations were 0 to 34.5 mg/liter and 0 to 61.6 mg/liter, respectively, in
      plasma and 0 to 35.4 mg/kg and 0 to 98.5 mg/kg, respectively, in feces. (This
      study is registered in the European Clinical Trials Database
      [https://eudract.ema.europa.eu/] under number EudraCT 2012 004921-25.). 

PMID- 25987639
TI  - Colistin and Fusidic Acid, a Novel Potent Synergistic Combination for Treatment
      of Multidrug-Resistant Acinetobacter baumannii Infections.
AB  - The spread of multidrug-resistant Acinetobacter baumannii (MDRAB) has led to the
      renaissance of colistin (COL), often the only agent to which MDRAB remains
      susceptible. Effective therapy with COL is beset with problems due to
      unpredictable pharmacokinetics, toxicity, and the rapid selection of resistance.
      Here, we describe a potent synergistic interaction when COL was combined with
      fusidic acid (FD) against A. baumannii. Synergy in vitro was assessed against 11
      MDRAB isolates using disc diffusion, checkerboard methodology (fractional
      inhibitory concentration index [FICI] of <= 0.5, susceptibility breakpoint index
      [SBPI] of >2), and time-kill methodology (>=2 log10 CFU/ml reduction). The
      ability of FD to limit the emergence of COL resistance was assessed in the
      presence and absence of each drug alone and in combination. Synergy was
      demonstrated against all strains, with an average FICI and SBPI of 0.064 and
      78.85, respectively. In time-kill assays, COL-FD was synergistic and rapidly
      bactericidal, including against COL-resistant strains. Fusidic acid prevented the
      emergence of COL resistance, which was readily selected with COL alone. This is
      the first description of a novel COL-FD regimen for the treatment of MDRAB. The
      combination was effective at low concentrations, which should be therapeutically
      achievable while limiting toxicity. Further studies are warranted to determine
      the mechanism underlying the interaction and the suitability of COL-FD as an
      unorthodox therapy for the treatment of multidrug-resistant Gram-negative
      infections. 

PMID- 25987640
TI  - Sensitization of Radiation or Gemcitabine-Based Chemoradiation Therapeutic Effect
      by Nimotuzumab in Pancreatic Cancer Cells.
AB  - This study was performed to observe the effect of the combination of nimotuzumab
      with radiation or gemcitabine-based chemoradiation on antipancreatic cancer cell
      therapy. Pancreatic cancer cells (PANC-1) were treated with nimotuzumab alone or
      combined with radiation (2, 4, or 8 Gy), which was either with or without
      gemcitabine chemotherapy. Cell proliferation, cell cycle distribution, and
      apoptosis were observed. The inhibition rate, the percentage of G2/M phase
      arrest, and the apoptosis rate of the combined nimotuzumab with radiation group
      was significantly higher than the group without nimotuzumab (P < .001). The
      inhibition rate, the percentage of G2/M phase, and the apoptosis rate of the
      nimotuzumab therapy combined with gemcitabine-based chemoradiation group were
      obviously higher than that in gemcitabine-based chemoradiation group (P < .001).
      In conclusion, nimotuzumab could enhance the anticancer effect of radiation and
      gemcitabine-based chemoradiation in PANC-1 cancer cells because of the
      enhancement of cell cycle arrest and apoptosis.

PMID- 25987641
TI  - Journaling as Therapy.

PMID- 25987644
TI  - Tamma PD et al (Clin Infect Dis 2015; 60:1319-25).

PMID- 25987642
TI  - Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency
      Oscillations in Cortical-Subcortical Networks in Humans: Evidence From Resting
      State Magnetoencephalography-Recordings.
AB  - Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been
      prominently implicated in the pathophysiology of schizophrenia (ScZ). The current
      study tested the effects of ketamine, a dissociative anesthetic and NMDA-R
      antagonist, on resting-state activity recorded with magnetoencephalography (MEG)
      in healthy volunteers. In a single-blind cross-over design, each participant (n =
      12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006
      mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level
      in the beta (13-30 Hz) and gamma (30-90 Hz) frequency ranges. In addition,
      connectivity analysis at source-level was performed using transfer entropy (TE).
      Ketamine increased gamma-power while beta-band activity was decreased.
      Specifically, elevated 30-90 Hz activity was pronounced in subcortical (thalamus
      and hippocampus) and cortical (frontal and temporal cortex) regions, whilst
      reductions in beta-band power were localized to the precuneus, cerebellum,
      anterior cingulate, temporal and visual cortex. TE analysis demonstrated
      increased information transfer in a thalamo-cortical network after ketamine
      administration. The findings are consistent with the pronounced dysregulation of
      high-frequency oscillations following the inhibition of NMDA-R in animal models
      of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients
      and increased functional connectivity during early illness stages. Moreover, our
      data highlight the potential contribution of thalamo-cortical connectivity
      patterns towards ketamine-induced neuronal dysregulation, which may be relevant
      for the understanding of ScZ as a disorder of disinhibition of neural circuits.

PMID- 25987645
TI  - The effectiveness of acupuncture versus clonazepam in patients with burning mouth
      syndrome.
AB  - OBJECTIVE: Burning mouth syndrome (BMS) is a chronic oral condition,
      characterised by burning symptoms, which mainly affects perimenopausal and
      postmenopausal women. Neuropathy might be the underlying cause of the condition.
      There are still insufficient data regarding successful therapy. The aim of this
      study was to compare the effectiveness of acupuncture and clonazepam. METHODS:
      Forty-two patients with BMS (38 women, 4 men) aged 66.7+/-12.0 years were
      randomly divided into two groups. Acupuncture was performed on 20 participants
      over 4 weeks, 3 times per week, on points ST8, GB2, TE21, SI19, SI18 and LI4
      bilaterally as well as GV20 in the midline, each session lasting half an hour.
      Twenty-two patients took clonazepam once a day (0.5 mg in the morning) for 2
      weeks and, after 2 weeks, two tablets (0.5 mg in the morning and in the evening)
      were taken for the next 2 weeks. Prior to and 1 month after either therapy,
      participants completed questionnaires: visual analogue scale, Beck Depression
      Inventory, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale,
      36-item Short Form Health Survey (SF-36) and Montreal Cognitive Assessment
      (MoCA). RESULTS: There were significant improvements in the scores of all outcome
      measures after treatment with both acupuncture and clonazepam, except for MoCA.
      There were no significant differences between the two therapeutic regimens
      regarding the scores of the performed tests. CONCLUSIONS: Acupuncture and
      clonazepam are similarly effective for patients with BMS.

PMID- 25987643
TI  - Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A
      Systematic Review and Meta-analysis of the Survival Benefit of Achieving a
      Sustained Virological Response.
AB  - BACKGROUND: Achievement of a sustained virologic response (SVR) after treatment
      for Hepatitis C infection is associated with improved outcomes. This meta
      analysis aimed to determine the impact of SVR on long-term mortality risk
      compared with nonresponders in a range of populations. METHODS: An electronic
      search identified all studies assessing all-cause mortality in SVR and non-SVR
      patients. Eligible articles were stratified into general, cirrhotic, and
      populations coinfected with human immunodeficiency virus. The adjusted hazard
      ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs
      non-SVR, and pooled estimates for the 5-year mortality in each group were
      calculated. RESULTS: 31 studies (n = 33 360) were identified as suitable for
      inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9-7.5)
      across all studies. The adjusted hazard ratio of mortality for patients achieving
      SVR vs non-SVR was 0.50 (95% CI, .37-.67) in the general population, 0.26 (95%
      CI, .18-.74) in the cirrhotic group, and 0.21 (.10-.45) in the coinfected group.
      The pooled 5-year mortality rates were significantly lower for patients achieving
      SVR compared with non-SVR in all 3 populations. CONCLUSIONS: The results suggest
      that there is a significant survival benefit of achieving an SVR compared with
      unsuccessful treatment in a range of populations infected with hepatitis C virus.

PMID- 25987646
TI  - A swallowed needle in a cat treated for feline hyperaesthesia syndrome.

PMID- 25987648
TI  - Evaluation of the Patterns of Care Provided to Patients With COPD Compared to
      Patients With Lung Cancer Who Died in Hospital.
AB  - INTRODUCTION: There is limited information about the end-of-life care provided to
      patients with end-stage chronic obstructive pulmonary disease (COPD) in
      comparison to patients with lung cancer. AIM AND METHODS: We compared the end-of
      life care provided to patients with COPD versus patients with lung cancer who
      died in hospital over a 12-month period in our institution. RESULTS: During the
      study period, 89 patients died due to COPD (n = 34) or lung cancer (n = 55).
      Compared to patients with lung cancer, patients with COPD received less
      palliative care services (50% vs 9%, P < .001) and underwent more diagnostic
      tests and received more life-prolonging measures. CONCLUSION: Toward the end of
      their life, patients with COPD received fewer symptom-alleviating treatments and
      palliative care services.

PMID- 25987647
TI  - Associations of Reducing Sedentary Time With Vascular Function and Insulin
      Sensitivity in Older Sedentary Adults.
AB  - BACKGROUND: We previously reported increased moderate-intensity (3-6 metabolic
      equivalents (METs)) physical activity (PA) reverses aging-associated vascular
      endothelial dysfunction, a surrogate marker of cardiovascular risk. Whether
      reductions in sedentary time alone contribute to this improvement is unknown.
      METHODS: Data from 96 adults (aged >=50 years) enrolled in a randomized control
      trial evaluating a 12-week intervention to increase PA in sedentary individuals
      were analyzed. Amount and intensity of activity were measured pre- and post
      intervention by step count and accelerometry. Subjects were divided into 3
      categories based on change in sedentary activity (<1. 5 METs): (i) >=5% reduction
      in sedentary time, (ii) 0-4.99% reduction, and (iii) increase sedentary time.
      Vascular endothelial function was measured by brachial artery flow-mediated
      dilation (FMD%) pre- and post-intervention. RESULTS: Sedentary time decreased
      overall (P = 0.001), with a 101-minute decrease in category 1 (N = 27, P <
      0.001), a 42-minute decrease in category 2 (N = 29, P = 0.003), and a 44-minute
      increase in category 3 (N = 40, P = 0.02). While FMD% increased in the entire
      study population (P = 0.008) over 12 weeks, no differences were observed between
      the categories (P = 0.73). In category 1, FMD% improvement was associated
      achievement of >=20 minutes/day of moderate intensity PA in bouts >= 10 minutes
      in length. CONCLUSIONS: Reductions of up to 100 minutes of sedentary time per day
      over 12 weeks was not significantly associated with improved vascular endothelial
      function in older adults. FMD% was significantly higher among those with lower
      sedentary behavior and concomitant moderate-intensity PA of >=20 minutes/day in
      bouts.

PMID- 25987649
TI  - Meta-analysis of incomplete microarray studies.
AB  - Meta-analysis of microarray studies to produce an overall gene list is relatively
      straightforward when complete data are available. When some studies lack
      information-providing only a ranked list of genes, for example-it is common to
      reduce all studies to ranked lists prior to combining them. Since this entails a
      loss of information, we consider a hierarchical Bayes approach to meta-analysis
      using different types of information from different studies: the full data
      matrix, summary statistics, or ranks. The model uses an informative prior for the
      parameter of interest to aid the detection of differentially expressed genes.
      Simulations show that the new approach can give substantial power gains compared
      with classical meta-analysis and list aggregation methods. A meta-analysis of 11
      published studies with different data types identifies genes known to be involved
      in ovarian cancer and shows significant enrichment. 

PMID- 25987650
TI  - Methods to assess an exercise intervention trial based on 3-level functional
      data.
AB  - Motivated by data recording the effects of an exercise intervention on subjects'
      physical activity over time, we develop a model to assess the effects of a
      treatment when the data are functional with 3 levels (subjects, weeks and days in
      our application) and possibly incomplete. We develop a model with 3-level mean
      structure effects, all stratified by treatment and subject random effects,
      including a general subject effect and nested effects for the 3 levels. The mean
      and random structures are specified as smooth curves measured at various time
      points. The association structure of the 3-level data is induced through the
      random curves, which are summarized using a few important principal components.
      We use penalized splines to model the mean curves and the principal component
      curves, and cast the proposed model into a mixed effects model framework for
      model fitting, prediction and inference. We develop an algorithm to fit the model
      iteratively with the Expectation/Conditional Maximization Either (ECME) version
      of the EM algorithm and eigenvalue decompositions. Selection of the number of
      principal components and handling incomplete data issues are incorporated into
      the algorithm. The performance of the Wald-type hypothesis test is also
      discussed. The method is applied to the physical activity data and evaluated
      empirically by a simulation study. 

PMID- 25987651
TI  - Clinical evaluation of a new pupil independent diffractive multifocal intraocular
      lens with a +2.75 D near addition: a European multicentre study.
AB  - PURPOSE: To evaluate the clinical outcomes after cataract surgery with
      implantation of a new diffractive multifocal intraocular lens (IOL) with a lower
      near addition (+2.75 D.). METHODS: 143 eyes of 85 patients aged between 40 years
      and 83 years that underwent cataract surgery with implantation of the multifocal
      IOL (MIOL) Tecnis ZKB00 (Abbott Medical Optics,Santa Ana, California, USA) were
      evaluated. Changes in uncorrected (uncorrected distance visual acuity,
      uncorrected intermediate visual acuity, uncorrected near visual acuity) and
      corrected (corrected distance visual acuity, corrected near visual acuity) logMAR
      distance, intermediate visual acuity and near visual acuity, as well as manifest
      refraction were evaluated during a 3-month follow-up. Additionally, patients were
      asked about photic phenomena and spectacle dependence. RESULTS: Postoperative
      spherical equivalent was within +/-0.50 D and +/-1.00 D of emmetropia in 78.1%
      and 98.4% of eyes, respectively. Postoperative mean monocular uncorrected
      distance visual acuity, uncorrected near visual acuity and uncorrected
      intermediate visual acuity was 0.20 LogMAR or better in 73.7%, 81.1% and 83.9% of
      eyes, respectively. All eyes achieved monocular corrected distance visual acuity
      of 0.30 LogMAR or better. A total of 100% of patients referred to be at least
      moderately happy with the outcomes of the surgery. Only 15.3% of patients
      required the use of spectacles for some daily activities postoperatively.
      CONCLUSIONS: The introduction of low add MIOLs follows a trend to increase
      intermediate visual acuity. In this study a near add of +2.75 D still reaches
      satisfying near results and leads to high patient satisfaction for intermediate
      visual acuity.

PMID- 25987652
TI  - Platinum segments: a new platinum chain for adjustable upper eyelid loading.
AB  - PURPOSE: Prospective study evaluating outcomes of individually sutured platinum
      segment chains in upper eyelid loading. METHODS: Single-centre, single-surgeon,
      prospective study. Upper eyelid loading with 0.4 and 0.2 g platinum segment
      chains for lagophthalmos. Segments were sutured to create a desired weight and
      attached to superior tarsus and distal levator aponeurosis following levator
      recession. PRIMARY OUTCOME MEASURES: improvement in lagophthalmos and
      complications. SECONDARY OUTCOME MEASURES: cosmesis of eyelid margin contour and
      implant prominence. Minimum 3-month follow-up. RESULTS: Eighteen eyelids of 17
      patients received segment chains (mean weight 1.2 g, range 0.8-1.6 g) and 3 for
      exchange of pre-existing gold weights. Median follow-up was 10 (range 6-17)
      months. Mean blink lagophthalmos improved from 7 (3-10) mm to 3 (0-6) mm
      (p<0.0001), and gentle closure from 3.2 (0-8) mm to 1.1 (0-4.9) mm (p=0.0004).
      Twelve patients (71%) reported no prominence, and the remainder, mild prominence
      only. The chain was graded as having no prominence in 78% (14/18) eyelids. Two
      required segment adjustments with removal of a single 0.2 g segment at 11 months
      and transfer of 0.4 g segment to the contralateral eyelid at 16 months,
      respectively. One complication (posterior, trans-conjunctival exposure above the
      superior border of the tarsal plate) was seen 12 months post surgery, requiring
      repositioning. CONCLUSIONS: Platinum segment chains provide benefits of platinum
      chains with additional advantages of postoperative adjustibility. They can be
      used as an addition to pre-existing in situ weights or chains. TRIAL REGISTRATION
      NUMBER: REC reference: 13/SW/0146. IRAS project ID: 119022.

PMID- 25987653
TI  - Gene of the month: MET.
AB  - The MET receptor tyrosine kinase and its ligand hepatocyte growth factor/scatter
      factor (HGF/SF) are potential therapeutic targets in many human malignancies,
      making this pathway an important focus of molecular and cancer research. MET
      mutations have been detected in various tumours. In addition, many tumour types
      demonstrate MET and HGF/SF overexpression and amplification. The MET signal
      transduction cascade is complex, and manifests in a broad spectrum of mitogenic
      and morphogenic functions, affecting cell proliferation, migration,
      differentiation, morphology and survival. Cancer cells commandeer the
      physiological functions of this signalling axis to facilitate invasion and
      metastasis. Significant progress has been made in the development of agents that
      inhibit MET-HGF/SF signalling. In this article, we outline the key features of
      the MET gene, its protein product and the ligand HGF/SF, to provide an overview
      of this important signalling pathway and offer a summary of the relevant
      pathological and clinical directions of research. 

PMID- 25987654
TI  - Correction.

PMID- 25987655
TI  - Genome-wide analysis links NFATC2 with asparaginase hypersensitivity.
AB  - Asparaginase is used to treat acute lymphoblastic leukemia (ALL); however,
      hypersensitivity reactions can lead to suboptimal asparaginase exposure. Our
      objective was to use a genome-wide approach to identify loci associated with
      asparaginase hypersensitivity in children with ALL enrolled on St. Jude
      Children's Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n
      = 498), and Total XVI (n = 271), or Children's Oncology Group protocols POG 9906
      (n = 222) and AALL0232 (n = 2163). Germline DNA was genotyped using the
      Affymetrix 500K, Affymetrix 6.0, or the Illumina Exome BeadChip array. In
      multivariate logistic regression, the intronic rs6021191 variant in nuclear
      factor of activated T cells 2 (NFATC2) had the strongest association with
      hypersensitivity (P = 4.1 * 10(-8); odds ratio [OR] = 3.11). RNA-seq data
      available from 65 SJCRH ALL tumor samples and 52 Yoruba HapMap samples showed
      that samples carrying the rs6021191 variant had higher NFATC2 expression compared
      with noncarriers (P = 1.1 * 10(-3) and 0.03, respectively). The top ranked
      nonsynonymous polymorphism was rs17885382 in HLA-DRB1 (P = 3.2 * 10(-6); OR =
      1.63), which is in near complete linkage disequilibrium with the HLA-DRB1*07:01
      allele we previously observed in a candidate gene study. The strongest risk
      factors for asparaginase allergy are variants within genes regulating the immune
      response. 

PMID- 25987656
TI  - A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone
      in upfront treatment of systemic AL amyloidosis.
AB  - The combination of cyclophosphamide/bortezomib/dexamethasone (CyBorD) showed
      early promise of high rates of hematologic responses tempered by studies showing
      the inability to overcome poor prognosis of advanced cardiac amyloidosis. Large
      studies are needed to clarify its role in light chain (AL) amyloidosis. We report
      the outcome of 230 patients treated frontline with CyBorD. Overall hematologic
      response rate was 60%, and in the 201 patients with measurable disease it was
      62%, with 43% achieving at least very good partial response (VGPR). Cardiac
      response was reached in 17% of patients and renal response in 25% of patients.
      Advanced cardiac stage III patients (amino-terminal pro-natriuretic peptide type
      B >8500 ng/L) had lower response rates (42%, >= VGPR 23%) and poorer survival
      (median, 7 months). Nevertheless, hematologic response improved survival in these
      subjects (67% at 2 years), showing the importance of striving for a good response
      even in this group. 

PMID- 25987657
TI  - Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of
      measurements before GVHD onset and treatment.
AB  - We identified plasma biomarkers that presaged outcomes in patients with
      gastrointestinal graft-versus-host disease (GVHD) by measuring 23 biomarkers in
      samples collected before initiation of treatment. Six analytes with the greatest
      accuracy in predicting grade 3-4 GVHD in the first cohort (74 patients) were then
      tested in a second cohort (76 patients). The same 6 analytes were also tested in
      samples collected at day 14 +/- 3 from 167 patients free of GVHD at the time.
      Logistic regression and calculation of an area under a receiver-operating
      characteristic (ROC) curve for each analyte were used to determine associations
      with outcome. Best models in the GVHD onset and landmark analyses were determined
      by forward selection. In samples from the second cohort, collected a median of 4
      days before start of treatment, levels of TIM3, IL6, and sTNFR1 had utility in
      predicting development of peak grade 3-4 GVHD (area under ROC curve, 0.88).
      Plasma ST2 and sTNFR1 predicted nonrelapse mortality within 1 year after
      transplantation (area under ROC curve, 0.90). In the landmark analysis, plasma
      TIM3 predicted subsequent grade 3-4 GVHD (area under ROC curve, 0.76). We
      conclude that plasma levels of TIM3, sTNFR1, ST2, and IL6 are informative in
      predicting more severe GVHD and nonrelapse mortality. 

PMID- 25987658
TI  - Intracranial hemorrhage in patients with brain metastases treated with
      therapeutic enoxaparin: a matched cohort study.
AB  - Venous thromboembolism occurs frequently in patients with cancer who have brain
      metastases, but there is limited evidence supporting the safety of therapeutic
      anticoagulation. To assess the risk for intracranial hemorrhage associated with
      the administration of therapeutic doses of low-molecular-weight heparin, we
      performed a matched, retrospective cohort study of 293 patients with cancer with
      brain metastases (104 with therapeutic enoxaparin and 189 controls). A blinded
      review of radiographic imaging was performed, and intracranial hemorrhages were
      categorized as trace, measurable, and significant. There were no differences
      observed in the cumulative incidence of intracranial hemorrhage at 1 year in the
      enoxaparin and control cohorts for measurable (19% vs 21%; Gray test, P = .97;
      hazard ratio, 1.02; 90% confidence interval [CI], 0.66-1.59), significant (21% vs
      22%; P = .87), and total (44% vs 37%; P = .13) intracranial hemorrhages. The risk
      for intracranial hemorrhage was fourfold higher (adjusted hazard ratio, 3.98; 90%
      CI, 2.41-6.57; P < .001) in patients with melanoma or renal cell carcinoma (N =
      60) than lung cancer (N = 153), but the risk was not influenced by the
      administration of enoxaparin. Overall survival was similar for the enoxaparin and
      control cohorts (8.4 vs 9.7 months; Log-rank, P = .65). We conclude that
      intracranial hemorrhage is frequently observed in patients with brain metastases,
      but that therapeutic anticoagulation does not increase the risk for intracranial
      hemorrhage. 

PMID- 25987660
TI  - Congenital defects in V(D)J recombination.
AB  - INTRODUCTION OR BACKGROUND: The V(D)J recombination is a DNA rearrangement
      process that generates the diversity of T and B lymphocyte immune repertoire. It
      proceeds through the generation of a DNA double-strand break (DNA-DSB) by the
      Rag1/2 lymphoid-specific factors, which is repaired by the non-homologous end
      joining (NHEJ) DNA repair pathway. V(D)J recombination also constitutes a
      checkpoint in the lymphoid development. SOURCES OF DATA: V(D)J recombination
      defect results in severe combined immune deficiency (SCID) with a lack of T and B
      lymphocytes. AREAS OF AGREEMENT: The V(D)J recombination represents one of the
      few programmed molecular events leading to DNA-DSBs that strictly relies on NHEJ.
      Two NHEJ factors, Artemis and XLF/Cernunnos, were identified through the
      molecular studies of SCID patients. Mutations in PRKDC and DNA Ligase IV genes
      also result in SCID. GROWING POINTS: Studies in mice have demonstrated that
      XLF/Cernunnos is dispensable for V(D)J recombination in lymphoid cells but not
      for the repair of genotoxic-induced DNA-DSBs, which raises the question of the
      implication of Rag1/2 factors in the DNA repair phase of V(D)J recombination.
      AREAS TIMELY FOR DEVELOPING RESEARCH: New factors of NHEJ, such as PAXX, are
      being identified. Patients with NHEJ deficiency (XRCC4) without immune deficiency
      were recently reported. We, therefore, may not have yet the complete picture of
      DNA-DSB repair in the context of V(D)J recombination.

PMID- 25987659
TI  - International phase 3 study of azacitidine vs conventional care regimens in older
      patients with newly diagnosed AML with >30% blasts.
AB  - This multicenter, randomized, open-label, phase 3 trial evaluated azacitidine
      efficacy and safety vs conventional care regimens (CCRs) in 488 patients age >=65
      years with newly diagnosed acute myeloid leukemia (AML) with >30% bone marrow
      blasts. Before randomization, a CCR (standard induction chemotherapy, low-dose
      ara-c, or supportive care only) was preselected for each patient. Patients then
      were assigned 1:1 to azacitidine (n = 241) or CCR (n = 247). Patients assigned to
      CCR received their preselected treatment. Median overall survival (OS) was
      increased with azacitidine vs CCR: 10.4 months (95% confidence interval [CI], 8.0
      12.7 months) vs 6.5 months (95% CI, 5.0-8.6 months), respectively (hazard ratio
      [HR] was 0.85; 95% CI, 0.69-1.03; stratified log-rank P = .1009). One-year
      survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively
      (difference, 12.3%; 95% CI, 3.5%-21.0%). A prespecified analysis censoring
      patients who received AML treatment after discontinuing study drug showed median
      OS with azacitidine vs CCR was 12.1 months (95% CI, 9.2-14.2 months) vs 6.9
      months (95% CI, 5.1-9.6 months; HR, 0.76; 95% CI, 0.60-0.96; stratified log-rank
      P = .0190). Univariate analysis showed favorable trends for azacitidine compared
      with CCR across all subgroups defined by baseline demographic and disease
      features. Adverse events were consistent with the well-established safety profile
      of azacitidine. Azacitidine may be an important treatment option for this
      difficult-to-treat AML population. This trial was registered at
      www.clinicaltrials.gov as #NCT01074047. 

PMID- 25987661
TI  - Neutrophil Gelatinase-Associated Lipocalin, a Novel Mineralocorticoid Biotarget,
      Mediates Vascular Profibrotic Effects of Mineralocorticoids.
AB  - Activation of the mineralocorticoid receptor has been shown to be deleterious in
      cardiovascular diseases (CVDs). We have recently shown that lipocalin 2 (Lcn2),
      or neutrophil gelatinase-associated lipocalin (NGAL), is a primary target of
      aldosterone/mineralocorticoid receptor in the cardiovascular system. Lcn2 is a
      circulating protein, which binds matrix metalloproteinase 9 and modulates its
      stability. We hypothesized that Lcn2 could be a mediator of
      aldosterone/mineralocorticoid receptor profibrotic effects in the cardiovascular
      system. Correlations between aldosterone and profibrotic markers, such as
      procollagen type I N-terminal peptide, were investigated in healthy subjects and
      subjects with abdominal obesity. The implication of Lcn2 in the mineralocorticoid
      pathway was studied using Lcn2 knockout mice subjected to a
      nephrectomy/aldosterone/salt (NAS) challenge for 4 weeks. In human subjects,
      NGAL/matrix metalloproteinase 9 was positively correlated with plasma aldosterone
      and fibrosis biomarkers. In mice, loss of Lcn2 prevented the NAS-induced increase
      of plasma procollagen type I N-terminal peptide, as well as the increase of
      collagen fibers deposition and collagen I expression in the coronary vessels and
      the aorta. The lack of Lcn2 also blunted the NAS-induced increase in systolic
      blood pressure. Ex vivo, treatment of human fibroblasts with recombinant Lcn2
      induced the expression of collagen I and the profibrotic galectin-3 and
      cardiotrophin-1 molecules. Our results showed that Lcn2 plays a key role in
      aldosterone/mineralocorticoid receptor-mediated vascular fibrosis. The clinical
      data indicate that this may translate in human patients. Lcn2 is, therefore, a
      new biotarget in cardiovascular fibrosis induced by mineralocorticoid activation.

PMID- 25987662
TI  - Refractory Hypertension: Evidence of Heightened Sympathetic Activity as a Cause
      of Antihypertensive Treatment Failure.
AB  - Refractory hypertension is an extreme phenotype of treatment failure defined as
      uncontrolled blood pressure in spite of >=5 classes of antihypertensive agents,
      including chlorthalidone and a mineralocorticoid receptor antagonist. A
      prospective evaluation of possible mechanisms of refractory hypertension has not
      been done. The goal of this study was to test for evidence of heightened
      sympathetic tone as indicated by 24-hour urinary normetanephrine levels, clinic
      and ambulatory heart rate (HR), HR variability, arterial stiffness as indexed by
      pulse wave velocity, and systemic vascular resistance compared with patients with
      controlled resistant hypertension. Forty-four consecutive patients, 15 with
      refractory and 29 with controlled resistant hypertension, were evaluated
      prospectively. Refractory hypertensive patients were younger (48+/-13.3 versus
      56.5+/-14.1 years; P=0.038) and more likely women (80.0 versus 51.9%; P=0.047)
      compared with patients with controlled resistant hypertension. They also had
      higher urinary normetanephrine levels (464.4+/-250.2 versus 309.8+/-147.6 ug per
      24 hours; P=0.03), higher clinic HR (77.8+/-7.7 versus 68.8+/-7.6 bpm; P=0.001)
      and 24-hour ambulatory HR (77.8+/-7.7 versus 68.8+/-7.6; P=0.0018), higher pulse
      wave velocity (11.8+/-2.2 versus 9.4+/-1.5 m/s; P=0.009), reduced HR variability
      (4.48 versus 6.11; P=0.03), and higher systemic vascular resistance (3795+/-1753
      versus 2382+/-349 dyne.s.cm(5).m(2); P=0.008). These findings are consistent with
      heightened sympathetic tone being a major contributor to antihypertensive
      treatment failure and highlight the need for effective sympatholytic therapies in
      patients with refractory hypertension. 

PMID- 25987663
TI  - The Central Role of Neutrophil Gelatinase-Associated Lipocalin in Cardiovascular
      Fibrosis.

PMID- 25987664
TI  - Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset
      Chronic Kidney Disease in the Japanese General Population.
AB  - Whether long-term blood pressure (BP) variability among individuals without
      diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk,
      independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and
      metabolic profile changes during follow-up, remains uncertain. We used data from
      a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7
      years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration
      rate <60 mL/min per 1.73 m2 or proteinuria by dipstick). BP was measured at
      baseline and during 3 annual follow-up visits (4 visits). BP variability was
      defined as standard deviation (SD) and average real variability during the 4
      visits. At the year 3 follow-up visit, 6.3% of the population had developed CKD.
      In multivariable-adjusted logistic regression models, 1 SD increases in SDSBP
      (per 5 mmHg), SDDBP (per 3 mmHg), average real variabilitySBP (per 6 mmHg), and
      average real variabilityDBP (per 4 mmHg) were associated with new-onset CKD (odds
      ratios [ORs] and 95% confidence intervals, 1.15 [1.11-1.20], 1.08 [1.04-1.12],
      1.13 [1.09-1.17], 1.06 [1.02-1.10], respectively; all P<0.01) after adjustment
      for clinical characteristics, and with mean BP from year 0 to year 3. The
      associations of SDBP and average real variabilityBP with CKD remained significant
      after additional adjustments for metabolic parameter changes during follow-up
      (ORs, 1.06-1.15; all P<0.01). Sensitivity analyses by sex, antihypertensive
      medication use, and the presence of hypertension showed similar conclusions.
      Among those in the middle-aged and elderly general population without diabetes
      mellitus, long-term BP variability during 3 years was associated with new-onset
      CKD risk, independently of mean or cumulative exposure to BP and metabolic
      profile changes during follow-up. 

PMID- 25987665
TI  - Elevated Endothelial Hypoxia-Inducible Factor-1alpha Contributes to Glomerular
      Injury and Promotes Hypertensive Chronic Kidney Disease.
AB  - Hypertensive chronic kidney disease is one of the most prevalent medical
      conditions with high morbidity and mortality in the United States and worldwide.
      However, early events initiating the progression to hypertensive chronic kidney
      disease are poorly understood. We hypothesized that elevated endothelial hypoxia
      inducible factor-1alpha (HIF-1alpha) is a common early insult triggering initial
      glomerular injury leading to hypertensive chronic kidney disease. To test our
      hypothesis, we used an angiotensin II infusion model of hypertensive chronic
      kidney disease to determine the specific cell type and mechanisms responsible for
      elevation of HIF-1alpha and its role in the progression of hypertensive chronic
      kidney disease. Genetic studies coupled with reverse transcription polymerase
      chain reaction profiling revealed that elevated endothelial HIF-1alpha is
      essential to initiate glomerular injury and progression to renal fibrosis by the
      transcriptional activation of genes encoding multiple vasoactive proteins.
      Mechanistically, we found that endothelial HIF-1alpha gene expression was induced
      by angiotensin II in a nuclear factor-kappaB-dependent manner. Finally, we
      discovered reciprocal positive transcriptional regulation of endothelial Hif
      1alpha and Nf-kappab genes is a key driving force for their persistent activation
      and disease progression. Overall, our findings revealed that the stimulation of
      HIF-1alpha gene expression in endothelial cells is detrimental to induce kidney
      injury, hypertension, and disease progression. Our findings highlight early
      diagnostic opportunities and therapeutic approaches for hypertensive chronic
      kidney disease. 

PMID- 25987666
TI  - Hypoxia Represses ER-alpha Expression and Inhibits Estrogen-Induced Regulation of
      Ca2+-Activated K+ Channel Activity and Myogenic Tone in Ovine Uterine Arteries:
      Causal Role of DNA Methylation.
AB  - Previous in vivo study demonstrated that chronic hypoxia during gestation was
      associated with estrogen receptor-alpha (ER-alpha) gene repression in ovine
      uterine arteries. Yet, it remains undetermined whether hypoxia had a direct
      effect and if DNA methylation played a causal role in hypoxia-mediated ER-alpha
      gene repression. Thus, this study tested the hypothesis that prolonged hypoxia
      has a direct effect and increases promoter methylation resulting in ER-alpha gene
      repression and inhibition of estrogen-mediated adaptation of uterine vascular
      tone. Uterine arteries isolated from nonpregnant and pregnant sheep were treated
      ex vivo with 21.0% O2 and 10.5% O2 for 48 hours. Hypoxia significantly increased
      ER-alpha promoter methylation at both specificity protein-1 and upstream
      stimulatory factor binding sites, decreased specificity protein-1 and upstream
      stimulatory factor binding to the promoter, and suppressed ER-alpha expression in
      uterine arteries of pregnant animals. Of importance, the effects of hypoxia were
      blocked by a methylation inhibitor 5-aza-2'-deoxycytidine. In addition, hypoxia
      abrogated steroid hormone-mediated increase in ER-alpha expression and inhibited
      the hormone-induced increase in large-conductance Ca(2+)-activated K(+) channel
      activity and decrease in myogenic tone in uterine arteries of nonpregnant
      animals, which were reversed by 5-aza-2'-deoxycytidine. The results provide novel
      evidence of a direct effect of hypoxia on heightened promoter methylation that
      plays a causal role in ER-alpha gene repression and ablation of steroid hormone
      mediated adaptation of uterine arterial large conductance Ca(2+)-activated K(+)
      channel activity and myogenic tone in pregnancy. 

PMID- 25987668
TI  - Overlap between fibromyalgia tender points and Charcot's hysterical zones: A
      historical curiosity.

PMID- 25987669
TI  - Physician burnout: A neurologic crisis.

PMID- 25987667
TI  - Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult
      Population-Based Study.
AB  - Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an
      independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular
      calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known
      as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has
      been associated with various cardiovascular markers, cardiovascular outcomes, and
      mortality. In this study, we hypothesized that high levels of dp-ucMGP are
      associated with increased PWV. We recruited participants via a multicenter family
      based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by
      sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid
      and femoral pulse waveforms. Multiple regression analysis was performed to
      estimate associations between PWV and dp-ucMGP adjusting for age, renal function,
      and other cardiovascular risk factors. We included 1001 participants in our
      analyses (475 men and 526 women). Mean values were 7.87+/-2.10 m/s for PWV and
      0.43+/-0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both
      before and after adjustment for sex, age, body mass index, height, systolic and
      diastolic blood pressure (BP), heart rate, renal function, low- and high-density
      lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol
      lowering drugs, and history of cardiovascular disease (P<=0.01). In conclusion,
      high levels of dp-ucMGP are independently and positively associated with arterial
      stiffness after adjustment for common cardiovascular risk factors, renal
      function, and age. Experimental studies are needed to determine whether vitamin K
      supplementation slows arterial stiffening by increasing MGP carboxylation. 

PMID- 25987670
TI  - Challenges to ethics and professionalism facing the contemporary neurologist.

PMID- 25987671
TI  - Pearls & Oy-sters: Ocular motor abnormalities in bilateral paramedian thalamic
      stroke.

PMID- 25987672
TI  - Teaching NeuroImages: Drug-induced parkinsonism with asymmetrical putaminal DaT
      binding.

PMID- 25987673
TI  - Teaching NeuroImages: Giant fetal arachnoid cyst with favorable neurologic
      outcome.

PMID- 25987674
TI  - Effects of a Parent-Child Interactive Program for Families on Reducing the
      Exposure of School-Aged Children to Household Smoking.
AB  - INTRODUCTION: Parental smoking has been identified as the major source of
      children's exposure to environmental tobacco smoke (ETS). Therefore, parental
      involvement is critical in ETS exposure prevention programs. This study examined
      the effects of a parent-child interactive program on reducing children's exposure
      to ETS at home and enhancing parents' and children's prevention strategies.
      METHODS: A clustered randomized controlled trial was administered to 75 families
      of school-aged children from six primary schools in New Taipei City, Taiwan.
      Families in the intervention group received a parent-child interactive
      intervention, and parents in the control group received written materials on
      tobacco hazards. Data on children's exposure and the prevention of children's
      exposure to ETS at home were obtained at baseline, 8-week, and 20-week or 6-month
      assessments. RESULTS: The percentage of children with urine cotinine levels
      greater than or equal to 6 ng/ml was significantly lower in the intervention
      group than it was in the control group at both the 8-week and 6-month
      assessments. The intervention significantly reduced parental smoking in the
      presence of children and increased parents' prevention of children's ETS exposure
      and children's ETS avoidance behavior from the baseline to the 20-week
      assessment. CONCLUSIONS: This is a preliminary study design aimed at creating a
      program for reducing children's ETS exposure at home. Further research to produce
      evidence supporting the application of the parent-child interactive program in
      primary schools is suggested. The theoretical basis of the intervention design
      can serve as a reference for nursing education and the design of health education
      programs.

PMID- 25987675
TI  - The Effect of Polymorphisms in DNA Repair Genes and Carcinogen Metabolizers on
      Leukocyte Telomere Length: A Cohort of Healthy Spanish Smokers.
AB  - INTRODUCTION: Smoking implies exposure to carcinogenic agents that causes DNA
      damage, which could be suspected to enhance telomere attrition. To protect and
      deal with DNA damage, cells possess mechanisms that repair and neutralize harmful
      substances. Polymorphisms altering DNA repair capacity or carcinogen metabolism
      may lead to synergistic effects with tobacco carcinogen-induced shorter telomere
      length independently of cancer interaction. The aim of this study was to explore
      the association between leukocyte telomere length (LTL) and several genetic
      polymorphisms in DNA repair genes and carcinogen metabolizers in a cohort of
      healthy smokers. METHODS: We evaluated the effect of six genetic polymorphisms in
      cytochrome P1A1 (Ile462Val), XRCC1 (Arg399Gln), APEX1 (Asp148Glu), XRCC3
      (Thr241Met), and XPD (Asp312Asn; Lys751Gln) on LTL in a cohort of 145 healthy
      smokers in addition to smoking habits. RESULTS: Logistic regression analysis
      showed an association between XRCC1 399Gln allele and shorter telomere length (OR
      = 5.03, 95% CI = 1.08% to 23.36%). There were not association between the rest of
      polymorphisms analyzed and LTL. CONCLUSIONS: Continuous exposure to tobacco could
      overwhelm the DNA repair machinery, making the effect of the polymorphisms that
      reduce repair capacity more pronounced. Analyzing the function of smoking-induced
      DNA-repair genes and LTL is an important goal in order to identify therapeutic
      targets to treat smoking-induced diseases.

PMID- 25987676
TI  - Ivabradine approved for stable chronic heart failure.

PMID- 25987677
TI  - Study findings on acetaminophen at odds with clinical guidelines.

PMID- 25987678
TI  - Summaries of Safety Labeling Changes Approved By FDA-Boxed Warnings Highlights
      January-March 2015.

PMID- 25987679
TI  - Implementing mentoring into a pharmacy teaching and learning curriculum.

PMID- 25987680
TI  - Incorporating the Pharmacy Practice Model Initiative into advanced pharmacy
      practice experience rotations.

PMID- 25987681
TI  - Convulsions associated with moxifloxacin.

PMID- 25987683
TI  - A potential unexpected consequence of drug shortages on long-term prescribing
      patterns.

PMID- 25987682
TI  - Addressing potential interactions between antineoplastics and dietary
      supplements.

PMID- 25987684
TI  - Coping with death in the patient care setting.

PMID- 25987685
TI  - Finding and working with mentors.

PMID- 25987686
TI  - Oral acetylcysteine for neuropsychiatric disorders.

PMID- 25987687
TI  - Pharmacy leaders of tomorrow shaping practice today.

PMID- 25987688
TI  - Role of obinutuzumab in the treatment of chronic lymphocytic leukemia.
AB  - PURPOSE: The pharmacology, pharmacokinetics, safety and efficacy, and place in
      therapy of obinutuzumab in the treatment of chronic lymphocytic leukemia (CLL)
      are reviewed. SUMMARY: Obinutuzumab, a fully humanized monoclonal antibody that
      targets the CD20 receptor on mature B cells, was recently approved for use in
      combination with chlorambucil in patients with previously untreated CLL. In a
      Phase III clinical trial including 671 patients with CLL and significant
      comorbidities, patients who received obinutuzumab-chlorambucil combination
      therapy had longer median progression-free survival than those who received
      rituximab plus chlorambucil (26.7 months versus 15.2 months, p < 0.001) or
      chlorambucil alone (11.1 months, p < 0.001). Overall survival was also improved
      with the use of obinutuzumab-chlorambucil versus chlorambucil alone (hazard ratio
      for death, 0.41, p = 0.002) and similar to survival with the use of rituximab
      plus chlorambucil. The main type of adverse effect reported in association with
      obinutuzumab use is infusion-related reactions (IRRs), which occurred in 66% of
      patients in the Phase III trial, with 20% of reactions categorized as grade 3 or
      4; IRR risk can be reduced with appropriate dosing, premedication, patient
      monitoring, and immediate treatment of IRRs. Ongoing clinical trials are
      evaluating the effects of obinutuzumab in patients with newly diagnosed and
      relapsed or treatment-refractory CLL. CONCLUSION: In patients who are elderly or
      who have multiple comorbidities, the use of obinutuzumab, a CD20 monoclonal
      antibody, in combination with chlorambucil is an efficacious regimen for
      treatment-naive patients with symptomatic CLL.

PMID- 25987689
TI  - Case of antibiotic-associated diarrhea caused by Staphylococcus aureus
      enterocolitis.
AB  - PURPOSE: A case of Staphylococcus aureus enterocolitis (SEC) misdiagnosed as
      toxin-negative Clostridium difficile is reported. SUMMARY: An 82-year-old white
      man weighing 50 kg (body mass index, 16.8 kg/m(2)) was transported from an
      assisted living facility to the emergency department with the chief complaints of
      weakness, nausea, and diarrhea for one week and one bright-red stool on the
      morning of admission. Before hospital admission, he was treated for a urinary
      tract infection with ciprofloxacin 500 mg twice daily for 10 days. Stool cultures
      were negative for C. difficile but positive for S. aureus. The antimicrobial
      stewardship pharmacist recommended treatment with vancomycin 125 mg orally every
      6 hours for staphylococcal colitis. Oral vancomycin was discontinued after three
      doses on the morning of hospital day 8 after a gastroenterology consultation.
      Within 48 hours of the discontinuation of oral vancomycin, the patient had eight
      stools per day. Vancomycin was reinitiated and the patient's symptoms began to
      again improve. On hospital day 19, the patient was discharged with a prescription
      for 7 more days of therapy with vancomycin (to complete a 15-day course) and a
      diagnosis of toxin-negative C. difficile, despite having symptoms consistent with
      SEC and an enteric culture positive for S. aureus. CONCLUSION: An 82-year-old man
      was transferred from an assisted living facility to the hospital with profuse
      diarrhea and dehydration. Enteric cultures were positive for methicillin
      resistant S. aureus with multiple negative C. difficile toxin B assays.
      Appropriate therapy was delayed and the patient potentially misdiagnosed with
      toxin-negative C. difficile when the clinical symptoms and diagnostic testing
      were consistent with SEC.

PMID- 25987690
TI  - Subacute combined degeneration of the spinal cord in a patient abusing nitrous
      oxide and self-medicating with cyanocobalamin.
AB  - PURPOSE: A case of subacute combined degeneration (SCD) of the spinal cord
      manifesting as severe ataxia and urinary retention in a patient with a history of
      heavy nitrous oxide abuse and self-supplementation with cyanocobalamin is
      reported. SUMMARY: A 27-year-old woman was treated in the emergency department
      for complaints of abdominal pain and inability to urinate for about 12 hours. The
      patient also complained of worsening lower-extremity weakness for 10 days and a
      "pins and needles" sensation in the lower extremities for approximately 1 year.
      She reported nitrous oxide abuse over 3 years (an average of 100-200 "whippit"
      cartridges daily on 3 or 4 days per week), as well as long-term self-medication
      with oral and i.m. cyanocobalamin for the purpose of preventing nitrous oxide
      induced neurologic symptoms. Results of magnetic resonance imaging (MRI) were
      highly suggestive of SCD, which is typically seen in primary vitamin B12
      deficiency but has been reported in the context of chronic nitrous oxide
      exposure. Treatment was initiated with cyanocobalamin 1000 MUg i.m. daily, to be
      continued for 5 days and followed by a four-week regimen of 1000 MUg i.m. weekly.
      The patient was discharged after 3 days, despite continued symptoms, with
      instructions to obtain ongoing care but was lost to follow-up. CONCLUSION: A
      patient who abused nitrous oxide chronically developed ataxia, paresthesia, and
      urinary retention while self-medicating with cyanocobalamin. A diagnosis of SCD
      was supported by MRI findings, symptoms, and the known relationship between
      nitrous oxide exposure and vitamin B12 deficiency.

PMID- 25987692
TI  - Regulatory alerts for dietary supplements in Canada and the United States, 2005
      13.
AB  - PURPOSE: Dietary supplement regulatory alerts published by the Food and Drug
      Administration (FDA) and Health Canada were evaluated and characterized. METHODS:
      FDA MedWatch and Health Canada websites were reviewed to identify regulatory
      alerts regarding dietary supplements from January 1, 2005, through December 31,
      2013. Alerts were analyzed to identify product characteristics that may be
      predictive of product quality issues and potential patient harm. RESULTS: A total
      of 1560 dietary supplement-related regulatory alerts were identified. Of those,
      1287 (83%) were identified through Health Canada, and 273 (18%) were identified
      through FDA MedWatch. The country of origin of dietary supplements associated
      with regulatory alerts was not provided in most regulatory alerts; however, when
      their origin was provided, the United States was the most common. Dietary
      supplements intended for sexual enhancement were the subject of 33% of all
      regulatory alerts identified. Products purchased online were the most likely to
      be associated with a regulatory alert. Dietary supplements intended for sexual
      enhancement, weight loss, and bodybuilding or athletic performance appeared to
      pose the greatest risk for patient harm due to product contamination with a
      pharmaceutical such as a phosphodiesterase-5 inhibitor or sibutramine.
      CONCLUSION: Analysis of Canadian and U.S. regulatory alerts concerning dietary
      supplements revealed that more than 80% of the composite alerts were issued by
      Health Canada. The most common intended uses of supplements for which alerts were
      issued were sexual enhancement, weight loss, and bodybuilding or athletic
      performance. The most common reason for alerts was the presence of a
      pharmaceutical contaminant.

PMID- 25987691
TI  - Potential cytochrome P-450 drug-drug interactions in adults with metastatic solid
      tumors and effect on eligibility for Phase I clinical trials.
AB  - PURPOSE: Potential cytochrome P-450 (CYP) drug-drug interactions in adults with
      metastatic solid tumors and their effect on eligibility for Phase I clinical
      trials were characterized. METHODS: This study included adult patients with
      metastatic solid tumors seen by a medical oncologist from January 2008 through
      July 2011. The medications used by these patients were identified. Each
      medication's potential for interacting with CYP isozymes was also characterized.
      Medication changes required to meet Phase I trial eligibility criteria were also
      reviewed. RESULTS: Data from 1773 patients were analyzed: 1489 were not enrolled
      in a Phase I trial and 284 were enrolled in a Phase I trial. Polypharmacy was
      significantly more prevalent in the group enrolled in a Phase I trial compared
      with those not enrolled (95% versus 80%, p < 0.001). The majority of patients not
      enrolled in a Phase I trial were taking at least one CYP isozyme inhibitor (87%)
      and at least one CYP isozyme inducer (45%). In a separate analysis, four Phase I
      trials were evaluated. Of 295 screened patients, 3.2% could not enroll due to
      concurrent medications. Charts from 74 enrolled patients revealed 655 concurrent
      medications-93 medications required further review for eligibility involving 51
      (69%) of patients. Of the 93 medications, 38 (41%) were stopped and 41 (44%) were
      changed for the study. CONCLUSION: Polypharmacy and the use of medications that
      interact with CYP isoyzmes were common in adult patients with metastatic solid
      tumors. Patients enrolling in Phase I studies often require medication changes to
      meet eligibility requirements.

PMID- 25987693
TI  - Personal reflections 30 years after the Hilton Head Conference.

PMID- 25987695
TI  - Treatment Advances in Locoregionally Advanced and Stage IVB/Recurrent Cervical
      Cancer: Can We Agree That More Is Not Always Better?

PMID- 25987694
TI  - Efficacy of Prophylactic Low-Molecular Weight Heparin for Ambulatory Patients
      With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial.
AB  - PURPOSE: Advanced pancreatic cancer (APC), in addition to its high mortality,
      accounts for the highest rates of venous thromboembolic events (VTEs).
      Enoxaparin, a low-molecular weight heparin, is effective in prevention and
      treatment of VTEs. Some small studies have indicated that this benefit might
      extend to patients with cancer. PATIENTS AND METHODS: Patients with
      histologically proven APC were randomly assigned to ambulant first-line
      chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to
      investigate the probable reduction in symptomatic VTEs and the impact on
      survival. RESULTS: A total of 312 patients were recruited as one of the protocol
      end points was reached. Within the first 3 months, the numbers of symptomatic
      VTEs were as follows: 15 of 152 patients in the observation group and two of 160
      patients in the enoxaparin group (hazard ratio [HR], 0.12; 95% CI, 0.03 to 0.52;
      chi(2) P = .001). The numbers of major bleeding events were as follows: five of
      152 patients in the observation arm and seven of 160 patients in the enoxaparin
      arm (HR, 1.4; 95% CI, 0.35 to 3.72; chi(2) P = 1.0). Overall cumulative incidence
      rates of symptomatic VTEs were 15.1% (observation) and 6.4% (enoxaparin; HR,
      0.40; 95% CI, 0.19 to 0.83; P = .01). Progression-free (HR, 1.06; 95% CI, 0.84 to
      1.32; P = .64) and overall survival (HR, 1.01; 95% CI, 0.87 to 1.38; P = .44) did
      not differ between groups. CONCLUSION: This study demonstrates the high efficacy
      and feasibility of primary pharmacologic prevention of symptomatic VTEs in
      outpatients with APC. Treatment efficacy was not affected by simultaneous
      treatment with enoxaparin in this trial setting.

PMID- 25987696
TI  - To Better Understand Emotions of Bereaved Caregivers Who Took Care of Patients at
      Home.

PMID- 25987697
TI  - Assessing the Significance of BRCA1 and BRCA2 Mutations in Pancreatic Cancer.

PMID- 25987698
TI  - Reply to H. Nakayama et al.

PMID- 25987699
TI  - When to Offer Thromboprophylaxis to Patients With Advanced Pancreatic Cancer:
      Shedding Light on the Path Forward.

PMID- 25987700
TI  - Validation and Development of a Modified Breast Graded Prognostic Assessment As a
      Tool for Survival in Patients With Breast Cancer and Brain Metastases.
AB  - PURPOSE: Several indices have been developed to predict overall survival (OS) in
      patients with breast cancer with brain metastases, including the breast graded
      prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky
      performance score. However, number of brain metastases-a highly relevant clinical
      variable-is less often incorporated into the final model. We sought to validate
      the existing breast-GPA in an independent larger cohort and refine it integrating
      number of brain metastases. PATIENTS AND METHODS: Data were retrospectively
      gathered from a prospectively maintained institutional database. Patients with
      newly diagnosed brain metastases from 1996 to 2013 were identified. After
      validating the breast-GPA, multivariable Cox regression and recursive
      partitioning analysis led to the development of the modified breast-GPA. The
      performances of the breast-GPA and modified breast-GPA were compared using the
      concordance index. RESULTS: In our cohort of 1,552 patients, the breast-GPA was
      validated as a prognostic tool for OS (P < .001). In multivariable analysis of
      the breast-GPA and number of brain metastases (> three v <= three), both were
      independent predictors of OS. We therefore developed the modified breast-GPA
      integrating a fourth clinical parameter. Recursive partitioning analysis
      reinforced the prognostic significance of these four factors. Concordance indices
      were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast
      GPA and modified breast-GPA, respectively (P < .001). CONCLUSION: The modified
      breast-GPA incorporates four simple clinical parameters of high prognostic
      significance. This index has an immediate role in the clinic as a formative part
      of the clinician's discussion of prognosis and direction of care and as a
      potential patient selection tool for clinical trials.

PMID- 25987701
TI  - Trends in the Cost and Use of Targeted Cancer Therapies for the Privately Insured
      Nonelderly: 2001 to 2011.
AB  - PURPOSE: This study sought to define and identify drivers of trends in cost and
      use of targeted therapeutics among privately insured nonelderly patients with
      cancer receiving chemotherapy between 2001 and 2011. METHODS: We classified
      oncology drugs as targeted oral anticancer medications, targeted intravenous
      anticancer medications, and all others. Using the LifeLink Health Plan Claims
      Database, we studied and disaggregated trends in use and in insurance and out-of
      pocket payments per patient per month and during the first year of chemotherapy.
      RESULTS: We found a large increase in the use of targeted intravenous anticancer
      medications and a gradual increase in targeted oral anticancer medications;
      targeted therapies accounted for 63% of all chemotherapy expenditures in 2011.
      Insurance payments per patient per month and in the first year of chemotherapy
      for targeted oral anticancer medications more than doubled in 10 years,
      surpassing payments for targeted intravenous anticancer medications, which
      remained fairly constant throughout. Substitution toward targeted therapies and
      growth in drug prices both at launch and postlaunch contributed to payer spending
      growth. Out-of-pocket spending for targeted oral anticancer medications was <=
      half of the amount for targeted intravenous anticancer medications. CONCLUSION:
      Targeted therapies now dominate anticancer drug spending. More aggressive
      management of pharmacy benefits for targeted oral anticancer medications and
      payment reform for injectable drugs hold promise. Restraining the rapid rise in
      spending will require more than current oral drug parity laws, such as value
      based insurance that makes the benefits and costs transparent and involves the
      patient directly in the choice of treatment.

PMID- 25987702
TI  - Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior
      Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia.
AB  - PURPOSE: Survivors of childhood acute lymphoblastic leukemia (ALL) exhibit
      increased rates of neurocognitive deficits. This study was conducted to test
      whether interpatient variability in neurocognitive outcomes can be explained by
      polymorphisms in candidate genes conferring susceptibility to neurocognitive
      decline. METHODS: Neurocognitive testing was conducted in 350 pediatric leukemia
      survivors, treated on Dana-Farber Cancer Institute ALL Consortium Protocols 95-01
      or 00-01. Genomic DNA was isolated from bone marrow collected at remission.
      Candidate polymorphisms were selected on the basis of prior literature, targeting
      genes related to drug metabolism, oxidative damage, altered neurotransmission,
      neuroinflammation, and folate physiology. Single nucleotide polymorphisms were
      detected using either a customized multiplexed Sequenom MassARRAY assay or
      polymerase chain reaction-based allelic discrimination assays. Multivariable
      logistic regression models were used to estimate the effects of genotype on
      neurocognitive outcomes, adjusted for the effects of demographic and treatment
      variables. False-discovery rate correction was made for multiple hypothesis
      testing, indicated as a Q value. RESULTS: Inferior cognitive or behavioral
      outcomes were associated with polymorphisms in three genes related to oxidative
      stress and/or neuroinflammation: NOS3 (IQ, Q = 0.008; Vocabulary Q = 0.011;
      Matrix Reasoning Q = 0.008), SLCO2A1 (IQ Q = 0.043; Digit Span Q = 0.006; Block
      Design Q = 0.076), and COMT (Behavioral Assessment System for Children-2
      Attention Q = 0.080; and Hyperactivity Q = 0.084). Survivors homozygous for NOS3
      894T, with at least one SLCO2A1 variant G allele or with at least one GSTP1
      variant allele, had lower mean estimated IQ scores than those without these
      genotypes. CONCLUSION: These data are consistent with the hypothesis that
      oxidative damage contributes to chemotherapy-associated neurocognitive decline
      among children with leukemia.

PMID- 25987703
TI  - Pathogenic Leptospira interrogans exoproteins are primarily involved in
      heterotrophic processes.
AB  - Leptospirosis is a life-threatening and emerging zoonotic disease with a
      worldwide annual occurrence of more than 1 million cases. Leptospirosis is caused
      by spirochetes belonging to the genus Leptospira. The mechanisms of disease
      manifestation in the host remain elusive, and the roles of leptospiral
      exoproteins in these processes have yet to be determined. Our aim in this study
      was to assess the composition and quantity of exoproteins of pathogenic
      Leptospira interrogans and to construe how these proteins contribute to disease
      pathogenesis. Label-free quantitative mass spectrometry of proteins obtained from
      Leptospira spirochetes cultured in vitro under conditions mimicking infection
      identified 325 exoproteins. The majority of these proteins are conserved in the
      nonpathogenic species Leptospira biflexa, and proteins involved in metabolism and
      energy-generating functions were overrepresented and displayed the highest
      relative abundance in culture supernatants. Conversely, proteins of unknown
      function, which represent the majority of pathogen-specific proteins (presumably
      involved in virulence mechanisms), were underrepresented. Characterization of
      various L. interrogans exoprotein mutants in the animal infection model revealed
      host mortality rates similar to those of hosts infected with wild-type L.
      interrogans. Collectively, these results indicate that pathogenic Leptospira
      exoproteins primarily function in heterotrophic processes (the processes by which
      organisms utilize organic substances as nutrient sources) to maintain the
      saprophytic lifestyle rather than the virulence of the bacteria. The
      underrepresentation of proteins homologous to known virulence factors, such as
      toxins and effectors in the exoproteome, also suggests that disease manifesting
      from Leptospira infection is likely caused by a combination of the primary and
      potentially moonlight functioning of exoproteins. 

PMID- 25987704
TI  - Identifying Francisella tularensis genes required for growth in host cells.
AB  - Francisella tularensis is a highly virulent Gram-negative intracellular pathogen
      capable of infecting a vast diversity of hosts, ranging from amoebae to humans. A
      hallmark of F. tularensis virulence is its ability to quickly grow to high
      densities within a diverse set of host cells, including, but not limited to,
      macrophages and epithelial cells. We developed a luminescence reporter system to
      facilitate a large-scale transposon mutagenesis screen to identify genes required
      for growth in macrophage and epithelial cell lines. We screened 7,454 individual
      mutants, 269 of which exhibited reduced intracellular growth. Transposon
      insertions in the 269 growth-defective strains mapped to 68 different genes.
      FTT_0924, a gene of unknown function but highly conserved among Francisella
      species, was identified in this screen to be defective for intracellular growth
      within both macrophage and epithelial cell lines. FTT_0924 was required for full
      Schu S4 virulence in a murine pulmonary infection model. The DeltaFTT_0924 mutant
      bacterial membrane is permeable when replicating in hypotonic solution and within
      macrophages, resulting in strongly reduced viability. The permeability and
      reduced viability were rescued when the mutant was grown in a hypertonic
      solution, indicating that FTT_0924 is required for resisting osmotic stress. The
      DeltaFTT_0924 mutant was also significantly more sensitive to beta-lactam
      antibiotics than Schu S4. Taken together, the data strongly suggest that FTT_0924
      is required for maintaining peptidoglycan integrity and virulence. 

PMID- 25987706
TI  - Streptococcus pyogenes triggers activation of the human contact system by
      streptokinase.
AB  - Severe invasive infectious diseases remain a major and life-threatening health
      problem. In serious cases, a systemic activation of the coagulation cascade is a
      critical complication that is associated with high mortality rates. We report
      here that streptokinase, a group A streptococcal plasminogen activator, triggers
      the activation of the human contact system. Activation of contact system factors
      at the surface of the Streptococcus pyogenes serotype M49 is dependent on
      streptokinase and plasminogen. Our results also show that secreted streptokinase
      is an efficient contact system activator, independent from a contact surface.
      This results in the processing of high-molecular-weight kininogen and the release
      of bradykinin, a potent vascular mediator. We further investigated whether the
      ability of 50 different clinical S. pyogenes isolates to activate the contact
      system is associated with an invasive phenotype. The data reveal that isolates
      from invasive infections trigger an activation of the contact system more
      potently than strains isolated from noninvasive infections. The present study
      gives new insights into the mechanisms by which S. pyogenes triggers the human
      contact system and stresses the function of soluble and surface located plasmin
      exploited as a group A streptococcal virulence factor through the action of
      streptokinase.

PMID- 25987705
TI  - Colonization of epidermal tissue by Staphylococcus aureus produces localized
      hypoxia and stimulates secretion of antioxidant and caspase-14 proteins.
AB  - A partial-thickness epidermal explant model was colonized with green fluorescent
      protein (GFP)-expressing Staphylococcus aureus, and the pattern of S. aureus
      biofilm growth was characterized using electron and confocal laser scanning
      microscopy. The oxygen concentration in explants was quantified using
      microelectrodes. The relative effective diffusivity and porosity of the epidermis
      were determined using magnetic resonance imaging, while hydrogen peroxide (H2O2)
      concentration in explant media was measured by using microelectrodes. Secreted
      proteins were identified and quantified using elevated-energy mass spectrometry
      (MS(E)). S. aureus biofilm grows predominantly in lipid-rich areas around hair
      follicles and associated skin folds. Dissolved oxygen was selectively depleted (2
      to 3-fold) in these locations, but the relative effective diffusivity and
      porosity did not change between colonized and control epidermis. Histological
      analysis revealed keratinocyte damage across all the layers of colonized
      epidermis after 4 days of culture. The colonized explants released significantly
      (P < 0.01) more antioxidant proteins of both epidermal and S. aureus origin,
      consistent with elevated H2O2 concentrations found in the media from the
      colonized explants (P< 0.001). Caspase-14 was also elevated significantly in the
      media from the colonized explants. While H2O2 induces primary keratinocyte
      differentiation, caspase-14 is required for terminal keratinocyte differentiation
      and desquamation. These results are consistent with a localized biological impact
      from S. aureus in response to colonization of the skin surface. 

PMID- 25987707
TI  - Tim-3 induces Th2-biased immunity and alternative macrophage activation during
      Schistosoma japonicum infection.
AB  - T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been
      regarded as an important regulatory factor in both adaptive and innate immunity.
      Recently, Tim-3 was reported to be involved in Th2-biased immune responses in
      mice infected with Schistosoma japonicum, but the exact mechanism behind the
      involvement of Tim-3 remains unknown. The present study aims to understand the
      role of Tim-3 in the immune response against S. japonicum infection. Tim-3
      expression was determined by flow cytometry, and increased Tim-3 expression was
      observed on CD4(+) and CD8(+) T cells, NK1.1(+) cells, and CD11b(+) cells from
      the livers of S. japonicum-infected mice. However, the increased level of Tim-3
      was lower in the spleen than in the liver, and no increase in Tim-3 expression
      was observed on splenic CD8(+) T cells or CD11b(+) cells. The schistosome-induced
      upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK
      cell numbers in vitro and in vivo. Tim-3 antibody blockade led to upregulation of
      inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b(+) cells
      cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which
      are markers of M2 macrophages. In summary, we observed schistosome-induced
      expression of Tim-3 on critical immune cell populations, which may be involved in
      the Th2-biased immune response and alternative activation of macrophages during
      infection. 

PMID- 25987708
TI  - Cyclic di-GMP modulates gene expression in Lyme disease spirochetes at the tick
      mammal interface to promote spirochete survival during the blood meal and tick-to
      mammal transmission.
AB  - Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing
      and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and
      Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the
      contribution of these pathways to spirochete survival and gene regulation
      throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act
      of being acquired revealed that the absence of RpoS and the consequent
      derepression of tick-phase genes impart a Stay signal required for midgut
      colonization. In addition to the behavioral changes brought on by the RpoS-off
      state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by
      the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the
      blood meal. Prior studies attributed this dramatic phenotype to a metabolic
      lesion stemming from reduced glycerol uptake and utilization. In a head-to-head
      comparison, however, the B. burgdorferi Deltaglp mutant had a markedly greater
      capacity to survive tick feeding than B. burgdorferi Deltahk1 or Deltarrp1
      mutants, establishing unequivocally that glycerol metabolism is only one
      component of the protection afforded by c-di-GMP. Data presented herein suggest
      that the protective response mediated by c-di-GMP is multifactorial, involving
      chemotactic responses, utilization of alternate substrates for energy generation
      and intermediary metabolism, and remodeling of the cell envelope as a means of
      defending spirochetes against threats engendered during the blood meal.
      Expression profiling of c-di-GMP-regulated genes through the enzootic cycle
      supports our contention that the Hk1/Rrp1 TCS functions primarily, if not
      exclusively, in ticks. These data also raise the possibility that c-di-GMP
      enhances the expression of a subset of RpoS-dependent genes during nymphal
      transmission. 

PMID- 25987709
TI  - Immunoprofiling of the tryptophan-rich antigen family in Plasmodium vivax.
AB  - Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified
      in human and rodent malaria parasites. TRAgs have been proposed as candidate
      antigens for potential vaccines. The Plasmodium vivax TRAg (PvTRAg) family
      includes 36 members. Each PvTRAg contains a tryptophan-rich (TR) domain in the C
      terminal region. In this study, we recombinantly expressed all 36 PvTRAgs using a
      cell-free expression system, and, for the first time, profiled the IgG antibody
      responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40
      healthy individuals using protein microarray technology. The mean seropositive
      rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in
      this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13,
      PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG
      antibody, even in low-endemicity countries. In addition, the results of an
      immunofluorescence analysis suggest that PvTRAgs are, at least in part,
      associated with caveola-vesicle complexes, a unique structure of P. vivax
      infected erythrocytes. The mechanism of formation and the function of these
      abundant membrane structures are not known. Further investigation aimed at
      determining the functions of these proteins would lead to a better understanding
      of the blood-stage biology of P. vivax. 

PMID- 25987711
TI  - Hydathode trichomes actively secreting water from leaves play a key role in the
      physiology and evolution of root-parasitic rhinanthoid Orobanchaceae.
AB  - BACKGROUND AND AIMS: Root hemiparasites from the rhinanthoid clade of
      Orobanchaceae possess metabolically active glandular trichomes that have been
      suggested to function as hydathode trichomes actively secreting water, a process
      that may facilitate resource acquisition from the host plant's root xylem.
      However, no direct evidence relating the trichomes to water secretion exists, and
      carbon budgets associated with this energy-demanding process have not been
      determined. METHODS: Macro- and microscopic observations of the leaves of
      hemiparasitic Rhinanthus alectorolophus were conducted and night-time gas
      exchange was measured. Correlations were examined among the intensity of
      guttation, respiration and transpiration, and analysis of these correlations
      allowed the carbon budget of the trichome activity to be quantified. We examined
      the intensity of guttation, respiration and transpiration, correlations among
      which indicate active water secretion. KEY RESULTS: Guttation was observed on the
      leaves of 50 % of the young, non-flowering plants that were examined, and
      microscopic observations revealed water secretion from the glandular trichomes
      present on the abaxial leaf side. Night-time rates of respiration and
      transpiration and the presence of guttation drops were positively correlated,
      which is a clear indicator of hydathode trichome activity. Subsequent
      physiological measurements on older, flowering plants indicated neither intense
      guttation nor the presence of correlations, which suggests that the peak activity
      of hydathodes is in the juvenile stage. CONCLUSIONS: This study provides the
      first unequivocal evidence for the physiological role of the hydathode trichomes
      in active water secretion in the rhinanthoid Orobanchaceae. Depending on the
      concentration of organic elements calculated to be in the host xylem sap, the
      direct effect of water secretion on carbon balance ranges from close to neutral
      to positive. However, it is likely to be positive in the xylem-only feeding
      holoparasites of the genus Lathraea, which is closely related to Rhinanthus.
      Thus, water secretion by the hydathodes might be viewed as a physiological pre
      adaptation in the evolution of holoparasitism in the rhinanthoid lineage of
      Orobanchaceae.

PMID- 25987710
TI  - Roles of mitochondrial energy dissipation systems in plant development and
      acclimation to stress.
AB  - BACKGROUND: Plants are sessile organisms that have the ability to integrate
      external cues into metabolic and developmental signals. The cues initiate
      specific signal cascades that can enhance the tolerance of plants to stress, and
      these mechanisms are crucial to the survival and fitness of plants. The adaption
      of plants to stresses is a complex process that involves decoding stress inputs
      as energy-deficiency signals. The process functions through vast metabolic and/or
      transcriptional reprogramming to re-establish the cellular energy balance.
      Members of the mitochondrial energy dissipation pathway (MEDP), alternative
      oxidases (AOXs) and uncoupling proteins (UCPs), act as energy mediators and might
      play crucial roles in the adaption of plants to stresses. However, their roles in
      plant growth and development have been relatively less explored. SCOPE: This
      review summarizes current knowledge about the role of members of the MEDP in
      plant development as well as recent advances in identifying molecular components
      that regulate the expression of AOXs and UCPs. Highlighted in particular is a
      comparative analysis of the expression, regulation and stress responses between
      AOXs and UCPs when plants are exposed to stresses, and a possible signal cross
      talk that orchestrates the MEDP, reactive oxygen species (ROS), calcium
      signalling and hormone signalling. CONCLUSIONS: The MEDP might act as a cellular
      energy/metabolic mediator that integrates ROS signalling, energy signalling and
      hormone signalling with plant development and stress accumulation. However, the
      regulation of MEDP members is complex and occurs at transcriptional,
      translational, post-translational and metabolic levels. How this regulation is
      linked to actual fluxes through the AOX/UCP in vivo remains elusive.

PMID- 25987716
TI  - Evolution of Feeding Structures in the Marine Nematode Order Enoplida.
AB  - Marine nematodes of the order Enoplida may represent the earliest lineage of
      nematodes and have a variety of fixed and movable feeding structures in their
      stomas. This study used an 18S ribosomal RNA phylogeny of the orders Enoplida and
      Triplonchida (subclass Enoplia) to explore the evolution of these feeding
      structures in light of previous hypotheses based solely on morphology. The
      Enoplida and Triplonchida were found to be paraphyletic, as several taxa
      currently classified as Triplonchida, such as Rhabdodemania, were found to be
      part of the Enoplida clade. The position of Rhabdodemania within Enoplida was
      unclear, but a close relation to Enoplidae and Thoracostomopsidae was not
      supported, making it unlikely that its movable odontia are homologous with the
      mandibles of these families. A member of Anticomidae was well-supported as the
      base of the clade containing Phanodermatidae, Enoplidae, and Thoracostomopsidae,
      suggesting that taxa with buccal rods and mandibles evolved from nematodes with
      unarmed stomas. The Phanodermatidae were shown to be more closely related to the
      Enoplidae and Thoracostomopsidae than were the Leptosomatidae, suggesting that
      the buccal rods of the phanoderms (rather than the mandibular ridge/odontia
      complex of the Leptosomatidae), may be the origin of the mandibles. 

PMID- 25987717
TI  - Bronchoplastic closure as an alternative approach for tracheal reconstruction
      following resection of a massive tracheal tumour.
AB  - A 47-year old woman presented with large cell carcinoma with extensive lengthwise
      and circumferential invasion of the lower trachea. End-to-end anastomosis by
      suture lines alone may be impossible and even harmful, following tumour resection
      with such extensive tracheal involvement. Thus, we performed a successful
      tracheal reconstruction with bronchoplastic closure without complications or
      recurrence at 12-month follow-up. This case highlights the use of this technique
      for the closure of massive airway defects. 

PMID- 25987719
TI  - Erratum.

PMID- 25987718
TI  - Predictors of non-neoplastic lesions in lung tumours showing ground-glass opacity
      on thin-section computed tomography based on a multi-institutional prospective
      study?.
AB  - OBJECTIVES: Peripheral small lung tumours (LTs) showing ground-glass opacity
      (GGO) tend to be treated without preoperative histological diagnosis due to
      difficulty in obtaining tissue samples. Exclusion of non-neoplastic lesions
      (NNLs) is essential when considering non-surgical treatment such as stereotactic
      radiotherapy. Here, we sought to determine preoperative factors associated with
      NNLs in peripheral LTs using data from a prospective study that investigated the
      efficacy of lesser pulmonary resection (JCOG0804/WJOG4507L). METHODS: The key
      eligibility criteria of the study were as follows: (i) peripherally located
      definitive or suspected LC with maximum diameter <=2 cm and (ii) radiological non
      invasive tumour with consolidation/tumour ratio (CTR) of <=0.25 based on thin
      section computed tomography (CT). Among all the resected LTs, incidences of NNL
      and precancerous lesions were examined. Also, logistic regression analysis was
      conducted to investigate the predictors of NNL using maximum tumour dimension
      (<=1 cm/>1 cm) and CTR (0/>0) as an explanatory variable. RESULTS: Between May
      2009 and April 2011, 333 patients were prospectively enrolled from 51
      institutions into the study. Among 333 patients, 345 LTs were included in the
      analysis. There were 314 (91.0%) LCs, 17 (4.9%) precancerous lesions and 14
      (4.1%) non-cancerous lesions. Maximum tumour dimension <=1 cm was identified as a
      significant predictor of NNLs with logistic regression analysis. There were 10
      (8.6%) NNLs in 116 LT <=1 cm, but 4 (1.7%) NNLs in 229 LTs >1 cm. CONCLUSIONS:
      NNLs were found in only 4.1% of peripheral LTs with GGO. However, when the tumour
      diameter was <=1 cm, ~10% were NNLs, necessitating a histological diagnosis when
      non-surgical treatment was considered.

PMID- 25987721
TI  - What's in a Word? Concept mapping: a graphical tool to reinforce learning of
      epidemiological concepts.
AB  - Epidemiology is founded on central concepts and principles, essential for
      conducting, reporting and critically assessing epidemiological studies.
      Definitions of the many concepts used in the field can be found in textbooks and
      via the Dictionary of Epidemiology. However, central epidemiological concepts are
      labelled and used in multiple ways, leading to potential misunderstanding when
      communicating in different fora. The aim here is to describe collaborative
      concept mapping, and illustrate how it can be used in teaching and learning
      epidemiology. Concept mapping is a cognitive technique that is widely used in the
      education of medical and allied health professions as a tool for critical
      thinking, and to assimilate new knowledge, but it is still under-utilised in
      epidemiology. A specific concept map is defined by the aim and question in focus;
      it is thus framed by a context. The concept map is constructed using a set of
      concepts (nodes) that are linked with arrows or lines (links). Words and phrases
      (connective terms) are used to explain relationships between the concepts linked.
      Different domains can be interconnected by linking concepts in different areas
      (cross-links). The underlying structure of knowledge is often complex, and
      consequently concept maps can be constructed using different topological
      features. Here we provide an illustrative example of concept mapping, based on a
      set of 'basic' concepts introduced in a doctoral course in epidemiology. In
      summary, concept mapping is a compelling, active learning tool, which can promote
      shared deeper knowledge of concepts and their complex interconnections, thereby
      facilitating a better understanding of epidemiological research. 

PMID- 25987722
TI  - The impact of smoke-free legislation on educational differences in birth
      outcomes.
AB  - BACKGROUND: Smoke-free legislation may have positive effects on birth outcomes.
      Given that smoking and secondhand smoke during pregnancy vary with socioeconomic
      position, legislation may have greater effects in some socioeconomic groups. For
      this study, we evaluated the impact of a 2006 ban on smoking in public places in
      the Canadian province of Quebec on preterm birth, small-for-gestational-age birth
      and birth weight, and on educational differences in these birth outcomes.
      METHODS: We analysed data on singleton births in Quebec between 2003 and 2010.
      Logistic regression was used to model the association of smoke-free legislation
      with preterm birth (<37 weeks), very preterm birth (<34 weeks), small-for
      gestational-age birth (<10th centile for gestational age and sex), low birth
      weight (<2500 g) and mean birth weight, adjusting for secular trends before and
      after legislation. Interaction terms were included to assess differential effects
      by level of maternal education. RESULTS: Smoke-free legislation was associated
      with average reductions of 3.1 preterm births (95% CI 0.1 to 6.0), 2.3 very
      preterm births (95% CI 0.9 to 3.7), 5.9 small-for-gestational-age births (95% CI
      2.6 to 9.3) and 1.0 low birthweight infants (95% CI 0.4 to 1.6) per 1000 live
      births, as well as a 17.1 g increase in mean birth weight (95% CI 10.7 to 23.6).
      Legislation was associated with improved birth outcomes in all categories of
      maternal education. CONCLUSIONS: Smoke-free legislation in Quebec was associated
      with reductions in preterm and small-for-gestational-age births, and an increase
      in birth weight. There was no compelling evidence that legislation impacted
      educational gradients in birth outcomes.

PMID- 25987723
TI  - Migration, urbanisation and mortality: 5-year longitudinal analysis of the PERU
      MIGRANT study.
AB  - OBJECTIVE: To compare all-cause and cause-specific mortality among 3 distinct
      groups: within-country, rural-to-urban migrants, and rural and urban dwellers in
      a longitudinal cohort in Peru. METHODS: The PERU MIGRANT Study, a longitudinal
      cohort study, used an age-stratified and sex-stratified random sample of urban
      dwellers in a shanty town community in the capital city of Peru, rural dwellers
      in the Andes, and migrants from the Andes to the shanty town community.
      Participants underwent a questionnaire and anthropomorphic measurements at a
      baseline evaluation in 2007-2008 and at a follow-up visit in 2012-2013. Mortality
      was determined by death certificate or family interview. RESULTS: Of the 989
      participants evaluated at baseline, 928 (94%) were evaluated at follow-up (mean
      age 48 years; 53% female). The mean follow-up time was 5.1 years, totalling
      4732.8 person-years. In a multivariable survival model, and relative to urban
      dwellers, migrant participants had lower all cause mortality (HR=0.30; 95% CI
      0.12-0.78), and both the migrant (HR=0.07; 95% CI 0.01-0.41) and rural (HR=0.06;
      95% CI 0.01-0.62) groups had lower cardiovascular mortality. CONCLUSIONS:
      Cardiovascular mortality of migrants remains similar to that of the rural group,
      suggesting that rural-to-urban migrants do not appear to catch up with urban
      mortality in spite of having a more urban cardiovascular risk factor profile.

PMID- 25987725
TI  - SIRT1 deacetylates RORgammat and enhances Th17 cell generation.

PMID- 25987724
TI  - Functional loss of IkappaBepsilon leads to NF-kappaB deregulation in aggressive
      chronic lymphocytic leukemia.
AB  - NF-kappaB is constitutively activated in chronic lymphocytic leukemia (CLL);
      however, the implicated molecular mechanisms remain largely unknown. Thus, we
      performed targeted deep sequencing of 18 core complex genes within the NF-kappaB
      pathway in a discovery and validation CLL cohort totaling 315 cases. The most
      frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes
      IkappaBepsilon, a negative regulator of NF-kappaB in normal B cells. Strikingly,
      13 of these cases carried an identical 4-bp frameshift deletion, resulting in a
      truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE
      aberrations predominated in poor-prognostic patients and were associated with
      inferior outcome. Minor subclones and/or clonal evolution were also observed,
      thus potentially linking this recurrent event to disease progression. Compared
      with wild-type patients, NFKBIE-deleted cases showed reduced IkappaBepsilon
      protein levels and decreased p65 inhibition, along with increased phosphorylation
      and nuclear translocation of p65. Considering the central role of B cell receptor
      (BcR) signaling in CLL pathobiology, it is notable that IkappaBepsilon loss was
      enriched in aggressive cases with distinctive stereotyped BcR, likely
      contributing to their poor prognosis, and leading to an altered response to BcR
      inhibitors. Because NFKBIE deletions were observed in several other B cell
      lymphomas, our findings suggest a novel common mechanism of NF-kappaB
      deregulation during lymphomagenesis. 

PMID- 25987727
TI  - Amphibious hearing in ringed seals (Pusa hispida): underwater audiograms, aerial
      audiograms and critical ratio measurements.
AB  - Ringed seals (Pusa hispida) are semi-aquatic marine mammals with a circumpolar
      Arctic distribution. In this study, we investigate the amphibious hearing
      capabilities of ringed seals to provide auditory profiles for this species across
      the full range of hearing. Using psychophysical methods with two trained ringed
      seals, detection thresholds for narrowband signals were measured under quiet,
      carefully controlled environmental conditions to generate aerial and underwater
      audiograms. Masked underwater thresholds were measured in the presence of octave
      band noise to determine critical ratios. Results indicate that ringed seals
      possess hearing abilities comparable to those of spotted seals (Phoca largha) and
      harbor seals (Phoca vitulina), and considerably better than previously reported
      for ringed and harp seals. Best sensitivity was 49 dB re. 1 uPa (12.8 kHz) in
      water, and -12 dB re. 20 uPa (4.5 kHz) in air, rivaling the acute hearing
      abilities of some fully aquatic and terrestrial species in their respective
      media. Critical ratio measurements ranged from 14 dB at 0.1 kHz to 31 dB at 25.6
      kHz, suggesting that ringed seals--like other true seals--can efficiently extract
      signals from background noise across a broad range of frequencies. The work
      described herein extends similar research on amphibious hearing in spotted seals
      recently published by the authors. These parallel studies enhance our knowledge
      of the auditory capabilities of ice-living seals, and inform effective management
      strategies for these and related species in a rapidly changing Arctic
      environment.

PMID- 25987726
TI  - BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.
AB  - B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is
      essential for the homeostatic survival of mature B cells. Earlier in vitro
      experiments with inhibitors that block MEK 1 and 2 suggested that activation of
      ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival.
      However, these inhibitors are now known to also inhibit MEK5, which activates the
      related MAP kinase ERK5. In the present study, we demonstrated that BAFF-induced
      B cell survival was actually independent of ERK1/2 activation but required ERK5
      activation. Consistent with this, we showed that conditional deletion of ERK5 in
      B cells led to a pronounced global reduction in mature B2 B cell numbers, which
      correlated with impaired survival of ERK5-deficient B cells after BAFF
      stimulation. ERK5 was required for optimal BAFF up-regulation of Mcl1 and Bcl2a1,
      which are prosurvival members of the Bcl-2 family. However, ERK5 deficiency did
      not alter BAFF activation of the PI3-kinase-Akt or NF-kappaB signaling pathways,
      which are also important for BAFF to promote mature B cell survival. Our study
      reveals a critical role for the MEK5-ERK5 MAP kinase signaling pathway in BAFF
      induced mature B cell survival and homeostatic maintenance of B2 cell numbers.

PMID- 25987728
TI  - Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals.
AB  - Myoglobin (Mb) is an oxygen binding protein found in vertebrate skeletal muscle,
      where it facilitates intracellular transport and storage of oxygen. This protein
      has evolved to suit unique physiological needs in the muscle of diving
      vertebrates that express Mb at much greater concentrations than their terrestrial
      counterparts. In this study, we characterized Mb oxygen affinity (P50) from 25
      species of aquatic and terrestrial birds and mammals. Among diving species, we
      tested for correlations between Mb P50 and routine dive duration. Across all
      species examined, Mb P50 ranged from 2.40 to 4.85 mmHg. The mean P50 of Mb from
      terrestrial ungulates was 3.72+/-0.15 mmHg (range 3.70-3.74 mmHg). The P50 of
      cetaceans was similar to terrestrial ungulates ranging from 3.54 to 3.82 mmHg,
      with the exception of the melon-headed whale, which had a significantly higher
      P50 of 4.85 mmHg. Among pinnipeds, the P50 ranged from 3.23 to 3.81 mmHg and
      showed a trend for higher oxygen affinity in species with longer dive durations.
      Among diving birds, the P50 ranged from 2.40 to 3.36 mmHg and also showed a trend
      of higher affinities in species with longer dive durations. In pinnipeds and
      birds, low Mb P50 was associated with species whose muscles are metabolically
      active under hypoxic conditions associated with aerobic dives. Given the broad
      range of potential globin oxygen affinities, Mb P50 from diverse vertebrate
      species appears constrained within a relatively narrow range. High Mb oxygen
      affinity within this range may be adaptive for some vertebrates that make
      prolonged dives. 

PMID- 25987712
TI  - Species delimitation in plants using the Qinghai-Tibet Plateau endemic Orinus
      (Poaceae: Tridentinae) as an example.
AB  - BACKGROUND AND AIMS: Accurate identification of species is essential for the
      majority of biological studies. However, defining species objectively and
      consistently remains a challenge, especially for plants distributed in remote
      regions where there is often a lack of sufficient previous specimens. In this
      study, multiple approaches and lines of evidence were used to determine species
      boundaries for plants occurring in the Qinghai-Tibet Plateau, using the genus
      Orinus (Poaceae) as a model system for an integrative approach to delimiting
      species. METHODS: A total of 786 individuals from 102 populations of six
      previously recognized species were collected for niche, morphological and genetic
      analyses. Three plastid DNA regions (matK, rbcL and trnH-psbA) and one nuclear
      DNA region [internal transcribed space (ITS)] were sequenced. KEY RESULTS:
      Whereas six species had been previously recognized, statistical analyses based on
      character variation, molecular data and niche differentiation identified only two
      well-delimited clusters, together with a third possibly originating from
      relatively recent hybridization between, or historical introgression from, the
      other two. CONCLUSIONS: Based on a principle of integrative species delimitation
      to reconcile different sources of data, the results provide compelling evidence
      that the six previously recognized species of the genus Orinus that were examined
      should be reduced to two, with new circumscriptions, and a third, identified in
      this study, should be described as a new species. This empirical study highlights
      the value of applying genetic differentiation, morphometric statistics and
      ecological niche modelling in an integrative approach to re-circumscribing
      species boundaries. The results produce relatively objective, operational and
      unbiased taxonomic classifications of plants occurring in remote regions.

PMID- 25987729
TI  - One antenna, two antennae, big antennae, small: total antennae length, not
      bilateral symmetry, predicts odor-tracking performance in the American cockroach
      Periplaneta americana.
AB  - Determining the location of a particular stimulus is often crucial to an animal's
      survival. One way to determine the local distribution of an odor is to make
      simultaneous comparisons across multiple sensors. If the sensors detect
      differences in the distribution of an odor in space, the animal can then steer
      toward the source. American cockroaches, Periplaneta americana, have 4 cm long
      antennae and are thought to track odor plumes using a spatial sampling strategy,
      comparing the amount of odor detected between these bilateral sensors. However,
      it is not uncommon for cockroaches to lose parts of their antennae and still
      track a wind-borne odor to its source. We examined whether bilateral odor input
      is necessary to locate an odor source in a wind-driven environment and how the
      loss of increasing lengths of the antennae affects odor tracking. The tracking
      performances of individuals with two bilaterally symmetrical antennae of
      decreasing length were compared with antennal length-matched individuals with one
      antenna. Cockroaches with one antenna were generally able to track an odor plume
      to its source. In fact, the performances of unilaterally antennectomized
      individuals were statistically identical to those of their bilaterally
      symmetrical counterparts when the combined length of both antennae equaled the
      length of the single antenna of the antennectomized individuals. This suggests
      that the total length of available antennae influences odor tracking performance
      more than any specific piece of antenna, and that they may be doing something
      more complex than a simple bilateral comparison between their antennae. The
      possibility of an antenna-topic map is discussed. 

PMID- 25987730
TI  - Muscle contractile properties as an explanation of the higher mean power output
      in marmosets than humans during jumping.
AB  - The muscle mass-specific mean power output (PMMS,mean) during push-off in jumping
      in marmosets (Callithrix jacchus) is more than twice that in humans. In the
      present study it was tested whether this is attributable to differences in muscle
      contractile properties. In biopsies of marmoset m. vastus lateralis (VL) and m.
      gastrocnemius medialis (GM) (N=4), fibre-type distribution was assessed using
      fluorescent immunohistochemistry. In single fibres from four marmoset and nine
      human VL biopsies, the force-velocity characteristics were determined. Marmoset
      VL contained almost exclusively fast muscle fibres (>99.0%), of which 63% were
      type IIB and 37% were hybrid fibres, fibres containing multiple myosin heavy
      chains. GM contained 9% type I fibres, 44% type IIB and 47% hybrid muscle fibres.
      The proportions of fast muscle fibres in marmoset VL and GM were substantially
      larger than those reported in the corresponding human muscles. The curvature of
      the force-velocity relationships of marmoset type IIB and hybrid fibres was
      substantially flatter than that of human type I, IIA, IIX and hybrid fibres,
      resulting in substantially higher muscle fibre mass-specific peak power
      (PFMS,peak). Muscle mass-specific peak power output (PMMS,peak) values of
      marmoset whole VL and GM, estimated from their fibre-type distributions and force
      velocity characteristics, were more than twice the estimates for the
      corresponding human muscles. As the relative difference in estimated PMMS,peak
      between marmosets and humans is similar to that of PMMS,mean during push-off in
      jumping, it is likely that the difference in in vivo mechanical output between
      humans and marmosets is attributable to differences in muscle contractile
      properties. 

PMID- 25987731
TI  - Energy metabolism and cellular homeostasis trade-offs provide the basis for a new
      type of sensitivity to ocean acidification in a marine polychaete at a high-CO2
      vent: adenylate and phosphagen energy pools versus carbonic anhydrase.
AB  - Species distributions and ecology can often be explained by their physiological
      sensitivity to environmental conditions. Whilst we have a relatively good
      understanding of how these are shaped by temperature, for other emerging drivers,
      such as PCO2  we know relatively little. The marine polychaete Sabella
      spallanzanii increases its metabolic rate when exposed to high PCO2  conditions
      and remains absent from the CO2 vent of Ischia. To understand new possible
      pathways of sensitivity to CO2 in marine ectotherms, we examined the metabolic
      plasticity of S. spallanzanii exposed in situ to elevated PCO2  by measuring
      fundamental metabolite and carbonic anhydrase concentrations. We show that whilst
      this species can survive elevated PCO2  conditions in the short term, and
      exhibits an increase in energy metabolism, this is accompanied by a significant
      decrease in carbonic anhydrase concentration. These homeostatic changes are
      unlikely to be sustainable in the longer term, indicating S. spallanzanii may
      struggle with future high PCO2  conditions. 

PMID- 25987732
TI  - Physiological and molecular responses of the goldfish (Carassius auratus) kidney
      to metabolic acidosis, and potential mechanisms of renal ammonia transport.
AB  - Relative to the gills, the mechanisms by which the kidney contributes to ammonia
      and acid-base homeostasis in fish are poorly understood. Goldfish were exposed to
      a low pH environment (pH 4.0, 48 h), which induced a characteristic metabolic
      acidosis and an increase in total plasma [ammonia] but reduced plasma ammonia
      partial pressure (PNH3). In the kidney tissue, total ammonia, lactate and
      intracellular pH remained unchanged. The urinary excretion rate of net base under
      control conditions changed to net acid excretion under low pH, with contributions
      from both the NH4 (+) (~30%) and titratable acidity minus bicarbonate (~70%; TA
      HCO3 (-)) components. Inorganic phosphate (Pi), urea and Na(+) excretion rates
      were also elevated while Cl(-) excretion rates were unchanged. Renal alanine
      aminotransferase activity increased under acidosis. The increase in renal ammonia
      excretion was due to significant increases in both the glomerular filtration and
      the tubular secretion rates of ammonia, with the latter accounting for ~75% of
      the increase. There was also a 3.5-fold increase in the mRNA expression of renal
      Rhcg-b (Rhcg1) mRNA. There was no relationship between ammonia secretion and
      Na(+) reabsorption. These data indicate that increased renal ammonia secretion
      during acidosis is probably mediated through Rhesus (Rh) glycoproteins and occurs
      independently of Na(+) transport, in contrast to branchial and epidermal models
      of Na(+)-dependent ammonia transport in freshwater fish. Rather, we propose a
      model of parallel H(+)/NH3 transport as the primary mechanism of renal tubular
      ammonia secretion that is dependent on renal amino acid catabolism. 

PMID- 25987733
TI  - The function of resilin in honeybee wings.
AB  - The present work aimed to reveal morphological characteristics of worker honeybee
      (Apis mellifera) wings and demonstrate the function of resilin on camber changes
      during flapping flight. Detailed morphological investigation of the wings showed
      that different surface characteristics appear on the dorsal and ventral side of
      the honeybee wings and the linking structure connecting the forewing and hindwing
      plays an indispensable role in honeybee flapping flight. Resilin stripes were
      found on both the dorsal and ventral side of the wings, and resilin patches
      mostly existed on the ventral side. On the basis of resilin distribution, five
      flexion lines and three cambered types around the lines of passive deformation of
      the coupled-wing profile were obtained, which defined the deformation mechanism
      of the wing along the chord, i.e. concave, flat plate and convex. From a movie
      obtained using high-speed photography from three orthogonal views of free flight
      in honeybees, periodic changes of the coupled-wing profile were acquired and
      further demonstrated that the deformation mechanism is a fundamental property for
      variable deformed shapes of the wing profile during flapping flight, and, in
      particular, the flat wing profile achieves a nice transition between downstrokes
      and upstrokes. 

PMID- 25987734
TI  - Digesting pythons quickly oxidize the proteins in their meals and save the lipids
      for later.
AB  - Pythons digesting rodent meals exhibit up to 10-fold increases in their resting
      metabolic rate (RMR); this increase in RMR is termed specific dynamic action
      (SDA). Studies have shown that SDA is partially fueled by oxidizing dietary
      nutrients, yet it remains unclear whether the proteins and the lipids in their
      meals contribute equally to this energy demand. We raised two populations of mice
      on diets labeled with either [(13)C]leucine or [(13)C]palmitic acid to
      intrinsically enrich the proteins and lipids in their bodies, respectively. Ball
      pythons (Python regius) were fed whole mice (and pureed mice 3 weeks later),
      after which we measured their metabolic rates and the delta(13)C in the breath.
      The delta(13)C values in the whole bodies of the protein- and lipid-labeled mice
      were generally similar (i.e. 5.7+/-4.70/00 and 2.8+/-5.40/00, respectively) but
      the oxidative kinetics of these two macronutrient pools were quite different. We
      found that the snakes oxidized 5% of the protein and only 0.24% of the lipids in
      their meals within 14 days. Oxidation of the dietary proteins peaked 24 h after
      ingestion, at which point these proteins provided ~90% of the metabolic
      requirement of the snakes, and by 14 days the oxidation of these proteins
      decreased to nearly zero. The oxidation of the dietary lipids peaked 1 day later,
      at which point these lipids supplied ~25% of the energy demand. Fourteen days
      after ingestion, these lipids were still being oxidized and continued to account
      for ~25% of the metabolic rate. Pureeing the mice reduced the cost of gastric
      digestion and decreased SDA by 24%. Pureeing also reduced the oxidation of
      dietary proteins by 43%, but it had no effect on the rates of dietary lipid
      oxidation. Collectively, these results demonstrate that pythons are able to
      effectively partition the two primary metabolic fuels in their meals. This
      approach of uniquely labeling the different components of the diet will allow
      researchers to examine new questions about how and when animals use the nutrients
      in their meals. 

PMID- 25987735
TI  - Regional modulation of the response to glutathione in Hydra vulgaris.
AB  - In the presence of prey, or upon exposure to reduced glutathione (GSH), Hydra
      polyps open a mouth to ingest the captured prey and close it after feeding; at
      rest the mouth is not evident. In previous papers we have shown that GABA,
      glycine and NMDA modulate the mechanisms of mouth closure through ligand-gated
      ion-channel receptors that are similar to their mammalian analogues in terms of
      biochemical and pharmacological properties. In order to study the regional
      distribution of these receptors, we have applied the GSH assay to polyps
      amputated at different levels of the body column. The response to 1-10 umol l(-1)
      GSH of polyps lacking either peduncle and foot or the entire body columns (heads)
      was not different from control, whole animals. In the presence of GABA or
      muscimol, duration of the response was significantly decreased in heads; the
      decrease was suppressed by the GABA antagonists gabazine and bicuculline. By
      contrast, in animals lacking peduncle and foot, duration of the response did not
      vary upon GABA administration. Conversely, in the presence of glycine, duration
      of the response in heads preparations was similar to control, whereas in footless
      polyps, it was significantly reduced. The decrease was mimicked by the glycine
      agonists taurine and beta-alanine, and counteracted by strychnine. These results
      suggest a regional distribution of receptors to GABA and glycine in the
      neuromuscular circuitry modulating the feeding behaviour. 

PMID- 25987737
TI  - Interactive effects of early and later nutritional conditions on the adult
      antioxidant defence system in zebra finches.
AB  - In vertebrates, antioxidant defences comprise a mixture of endogenously produced
      components and exogenously obtained antioxidants that are derived mostly from the
      diet. It has been suggested that early-life micronutritional conditions might
      influence the way in which the antioxidant defence system operates, which could
      enable individuals to adjust the activity of the endogenous and exogenous
      components in line with their expected intake of dietary antioxidants if the
      future environment resembles the past. We investigated this possibility by
      experimentally manipulating the micronutrient content of the diet during
      different periods of postnatal development in the zebra finch (Taeniopygia
      guttata). Birds that had a low micronutrient diet during the growth phase
      initially had a lower total antioxidant capacity (TAC) than those reared under a
      high micronutrient diet, but then showed a compensatory response, so that by the
      end of the growth phase, the TAC of the two groups was the same. Interestingly,
      we found an interactive effect of micronutrient intake early and late in
      development: only those birds that continued with the same dietary treatment (low
      or high) throughout development showed a significant increase in their TAC during
      the period of sexual maturation. A similar effect was also found in the level of
      enzymatic antioxidant defences (glutathione peroxidase; GPx). No significant
      effects were found in the level of oxidative damage in lipids [malondialdehyde
      (MDA) levels]. These findings demonstrate the importance of early and late
      developmental conditions in shaping multiple aspects of the antioxidant system.
      Furthermore, they suggest that young birds may adjust their antioxidant defences
      to enable them to 'thrive' on diets rich or poor in micronutrients later in life.

PMID- 25987736
TI  - Cross-training in birds: cold and exercise training produce similar changes in
      maximal metabolic output, muscle masses and myostatin expression in house
      sparrows (Passer domesticus).
AB  - Maximal metabolic outputs for exercise and thermogenesis in birds presumably
      influence fitness through effects on flight and shivering performance. Because
      both summit (Msum, maximum thermoregulatory metabolic rate) and maximum (MMR,
      maximum exercise metabolic rate) metabolic rates are functions of skeletal muscle
      activity, correlations between these measurements and their mechanistic
      underpinnings might occur. To examine whether such correlations occur, we
      measured the effects of experimental cold and exercise training protocols for 3
      weeks on body (Mb) and muscle (Mpec) masses, basal metabolic rate (BMR), Msum,
      MMR, pectoralis mRNA and protein expression for myostatin, and mRNA expression of
      TLL-1 and TLL-2 (metalloproteinase activators of myostatin) in house sparrows
      (Passer domesticus). Both training protocols increased Msum, MMR, Mb and Mpec,
      but BMR increased with cold training and decreased with exercise training. No
      significant differences occurred for pectoralis myostatin mRNA expression, but
      cold and exercise increased the expression of TLL-1 and TLL-2. Pectoralis
      myostatin protein levels were generally reduced for both training groups. These
      data clearly demonstrate cross-training effects of cold and exercise in birds,
      and are consistent with a role for myostatin in increasing pectoralis muscle mass
      and driving organismal increases in metabolic capacities. 

PMID- 25987738
TI  - Fluctuating temperatures and ectotherm growth: distinguishing non-linear and time
      dependent effects.
AB  - Most terrestrial ectotherms experience diurnal and seasonal variation in
      temperature. Because thermal performance curves are non-linear, mean performance
      can differ in fluctuating and constant thermal environments. However, time
      dependent effects--effects of the order and duration of exposure to temperature-
      can also influence mean performance. We quantified the non-linear and time
      dependent effects of diurnally fluctuating temperatures for larval growth rates
      in the tobacco hornworm, Manduca sexta L., with four main results. First, the
      shape of the thermal performance curve for growth rate depended on the duration
      of exposure: for example, optimal temperature and thermal breadth were greater
      for growth rates measured over short (24 h during the last instar) compared with
      long (the entire period of larval growth) time periods. Second, larvae reared in
      diurnally fluctuating temperatures had significantly higher optimal temperatures
      and maximal growth rates than larvae reared in constant temperatures. Third, for
      larvae maintained at three mean temperatures (20, 25 and 30 degrees C) and three
      diurnal temperature ranges (+/-0, +/-5 and +/-10 degrees C), diurnal fluctuations
      had opposite effects on mean growth rates at low versus high mean temperature.
      Fourth, both short- and long-term thermal performance curves yielded poor
      predictions of the non-linear effects of fluctuating temperature on mean growth
      rates (compared with our experimental results) at higher mean temperatures. Our
      results suggest caution in using constant temperature studies to model the
      consequences of variable thermal environments.

PMID- 25987739
TI  - Diverse dose-response effects of yolk androgens on embryo development and
      nestling growth in a wild passerine.
AB  - Avian egg yolks contain various amounts of maternally derived androgens that can
      modify offspring phenotype and adjust their development to the post-hatching
      environment. Seemingly adaptive variation in yolk androgen levels with respect to
      breeding density conditions or male attractiveness has been found in numerous
      studies. One important consideration that has been overlooked in previous
      research is the likely non-linear nature of hormone effects. To examine possible
      complex dose-response effects of maternal androgens on chick development, we
      experimentally administered three different androgen doses of the naturally
      occurring mixture of yolk testosterone and androstenedione to spotless starling
      eggs (Sturnus unicolor). We found that yolk androgens induce a non-linear dose
      response pattern in several traits. Androgens had a stimulatory effect on
      hatchling body mass and nestling skeletal growth, but maximum values were found
      at intermediate doses, whereas our highest dose resulted in a decrease. However,
      the opposite U-shaped effect was found on nestling body mass. We also detected
      linear negative and positive effects on embryonic development period and nestling
      gape width, respectively. Our results suggest differential tissue responsiveness
      to yolk androgens, which may result in compromises in maternal allocation to
      produce adapted phenotypes. Because of the non-linear dose-response pattern,
      future investigations should carefully consider a wide range of concentrations,
      as the balance of costs and benefits may strongly differ depending on
      concentration. 

PMID- 25987740
TI  - Optimal T Cell Activation and B Cell Antibody Responses In Vivo Require the
      Interaction between Leukocyte Function-Associated Antigen-1 and Kindlin-3.
AB  - Kindlin-3 is an important integrin regulator that is mutated in the rare genetic
      disorder, leukocyte adhesion deficiency type III, a disorder characterized by
      defective neutrophil trafficking and platelet function, leading to recurrent
      bacterial infections and bleeding. Kindlin-3 is also known to regulate T cell
      adhesion in vitro and trafficking in vivo, but whether the integrin/kindlin
      interaction regulates T or B cell activation in vivo is unclear. In this study,
      we used TTT/AAA beta2-integrin knock-in (KI) mice and TCR-transgenic (OT-II) KI
      mice, in which the integrin/kindlin connection is disrupted, to investigate the
      role of the integrin/kindlin interaction in T cell activation. We show that basal
      T cell activation status in these animals in vivo is normal, but they display
      reduced T cell activation by wild-type Ag-loaded dendritic cells in vitro. In
      addition, T cell activation in vivo is reduced. We also show that basal Ab levels
      are normal in TTT/AAA beta2-integrin KI mice, but B cell numbers in lymph nodes
      and IgG and IgM production after immunization are reduced. In conclusion, we show
      that the integrin/kindlin interaction is required for trafficking of immune
      cells, as well as for T cell activation and B cell Ab responses in vivo. These
      results imply that the immunodeficiency found in leukocyte adhesion deficiency
      type III patients, in addition to being caused by defects in neutrophil function,
      may be due, in part, to defects in lymphocyte trafficking and activation. 

PMID- 25987741
TI  - Novel Human Cytomegalovirus Viral Chemokines, vCXCL-1s, Display Functional
      Selectivity for Neutrophil Signaling and Function.
AB  - Human CMV (HCMV) uses members of the hematopoietic system including neutrophils
      for dissemination throughout the body. HCMV encodes a viral chemokine, vCXCL-1,
      that is postulated to attract neutrophils for dissemination within the host. The
      gene encoding vCXCL-1, UL146, is one of the most variable genes in the HCMV
      genome. Why HCMV has evolved this hypervariability and how this affects the
      virus' dissemination and pathogenesis is unknown. Because the vCXCL-1
      hypervariability maps to important binding and activation domains, we
      hypothesized that vCXCL-1s differentially activate neutrophils, which could
      contribute to HCMV dissemination, pathogenesis, or both. To test whether these
      viral chemokines affect neutrophil function, we generated vCXCL-1 proteins from
      11 different clades from clinical isolates from infants infected congenitally
      with HCMV. All vCXCL-1s were able to induce calcium flux at a concentration of
      100 nM and integrin expression on human peripheral blood neutrophils, despite
      differences in affinity for the CXCR1 and CXCR2 receptors. In fact, their
      affinity for CXCR1 or CXCR2 did not correlate directly with chemotaxis, G protein
      dependent and independent (beta-arrestin-2) activation, or secondary chemokine
      (CCL22) expression. Our data suggest that vCXCL-1 polymorphisms affect the
      binding affinity, receptor usage, and differential peripheral blood neutrophil
      activation that could contribute to HCMV dissemination and pathogenesis. 

PMID- 25987743
TI  - Siglec-G Deficiency Leads to Autoimmunity in Aging C57BL/6 Mice.
AB  - Siglec-G, a member of the sialic acid-binding Ig-like lectin (Siglec) family, is
      expressed on B cell and dendritic cell surfaces. It acts as an inhibitory
      coreceptor and modulates B cell activation, especially on B1 cells, as Siglec-G
      deficient mice show mainly a B1 cell-restricted phenotype resulting in increased
      B1 cell numbers. Although higher B1 cell numbers are discussed to be associated
      with autoimmunity, loss of Siglec-G does not result in autoimmune disease in
      BALB/c mice. However, there is evidence from Siglec-G * CD22 double-deficient
      mice and Siglec-G(-/-) mice on an autoimmune-prone MRL/lpr background that Siglec
      G is important to maintain tolerance in B cells. In this study, we analyzed the
      role of Siglec-G in induction and maintenance of B cell tolerance on C57BL/6
      background and in the FcgammaRIIb-deficient background. We find that aging Siglec
      G-deficient and Siglec-G * FcgammaRIIb double-deficient mice develop an
      autoimmune phenotype with elevated autoantibody levels and mild
      glomerulonephritis. Aging Siglec-G-deficient mice have elevated numbers of plasma
      cells and germinal center B cells, as well as a higher number of activated CD4 T
      cells, which likely all contribute to autoantibody production. Additional loss of
      the inhibitory receptor FcgammaRIIb in Siglec-G(-/-) mice does not result in
      exacerbation of disease. These results indicate that Siglec-G is important to
      maintain tolerance in B cells and prevent autoimmunity. 

PMID- 25987744
TI  - Treatment with Recombinant Trichinella spiralis Cathepsin B-like Protein
      Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch
      from M1 to M2 Macrophages.
AB  - Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key
      role, can cause high morbidity and mortality. The switch from classically (M1) to
      alternatively (M2) activated macrophages, which is dependent on the activation of
      STAT6 signaling, has been shown to protect organs from I/R injuries. In the
      current study, the effects of recombinant Trichinella spiralis cathepsin B-like
      protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to
      macrophage phenotypes switch were investigated. In a mouse I/R model undergoing
      60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated
      that intestinal I/R caused significant intestinal injury and induced a switch
      from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers
      (arginase-1 and found in inflammatory zone protein), an increase in levels of M1
      markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1
      macrophages. RTsCPB reversed intestinal I/R-induced M2-M1 transition and promoted
      M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an
      increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB
      significantly ameliorated intestinal injury and improved intestinal function and
      survival rate of animals, accompanied by a decrease in neutrophil infiltration
      and an increase in cell proliferation in the intestine. However, a selective
      STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by
      inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury
      causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal
      injury by promoting STAT6-dependent M1 to M2 transition. 

PMID- 25987742
TI  - Glucocorticoid-Augmented Efferocytosis Inhibits Pulmonary Pneumococcal Clearance
      in Mice by Reducing Alveolar Macrophage Bactericidal Function.
AB  - Inhaled corticosteroids (ICS) increase community-acquired pneumonia (CAP)
      incidence in patients with chronic obstructive pulmonary disease (COPD) by
      unknown mechanisms. Apoptosis is increased in the lungs of COPD patients. Uptake
      of apoptotic cells (ACs) ("efferocytosis") by alveolar macrophages (AMos) reduces
      their ability to combat microbes, including Streptococcus pneumoniae, the most
      common cause of CAP in COPD patients. Having shown that ICS significantly
      increase AMo efferocytosis, we hypothesized that this process, termed
      glucocorticoid-augmented efferocytosis, might explain the association of CAP with
      ICS therapy in COPD. To test this hypothesis, we studied the effects of
      fluticasone, AC, or both on AMos of C57BL/6 mice in vitro and in an established
      model of pneumococcal pneumonia. Fluticasone plus AC significantly reduced TLR4
      stimulated AMo IL-12 production, relative to either treatment alone, and
      decreased TNF-alpha, CCL3, CCL5, and keratinocyte-derived chemoattractant/CXCL1,
      relative to AC. Mice treated with fluticasone plus AC before infection with
      viable pneumococci developed significantly more lung CFUs at 48 h. However, none
      of the pretreatments altered inflammatory cell recruitment to the lungs at 48 h
      postinfection, and fluticasone plus AC less markedly reduced in vitro mediator
      production to heat-killed pneumococci. Fluticasone plus AC significantly reduced
      in vitro AMo killing of pneumococci, relative to other conditions, in part by
      delaying phagolysosome acidification without affecting production of reactive
      oxygen or nitrogen species. These results support glucocorticoid-augmented
      efferocytosis as a potential explanation for the epidemiological association of
      ICS therapy of COPD patients with increased risk for CAP, and establish murine
      experimental models to dissect underlying molecular mechanisms. 

PMID- 25987746
TI  - Effects of iodinated contrast agent, xylocaine and gadolinium concentration on
      the signal emitted in magnetic resonance arthrography: a samples study.
AB  - OBJECTIVE: To investigate the effects of dilution of paramagnetic contrast agent
      with iodinated contrast and xylocaine on the signal intensity during magnetic
      resonance arthrography, and to improve the paramagnetic contrast agent
      concentration utilized in this imaging modality. MATERIALS AND METHODS: Samples
      specially prepared for the study with three different concentrations of
      paramagnetic contrast agent diluted in saline, iodinated contrast agent and
      xylocaine were imaged with fast spin echo T1-weighted sequences with fat
      saturation. The samples were placed into flasks and graphical analysis of the
      signal intensity was performed as a function of the paramagnetic contrast
      concentration. RESULTS: As compared with samples of equal concentrations diluted
      only with saline, the authors have observed an average signal intensity decrease
      of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the
      increased gadolinium concentration in the samples caused decrease in signal
      intensity with all the dilutions. CONCLUSION: Minimizing the use of iodinated
      contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5
      mmol/L diluted in saline will improve the sensitivity of magnetic resonance
      arthrography.

PMID- 25987747
TI  - Multidetector computed tomography in the preoperative staging of gastric
      adenocarcinoma.
AB  - OBJECTIVE: To evaluate the role of multidetector computed tomography in the
      preoperative investigation of tumor invasion depth and lymph node and metastatic
      involvement according to the TNM classification, in patients with gastric
      adenocarcinoma. MATERIALS AND METHODS: Fifty-four patients with biopsy-confirmed
      gastric cancer underwent preoperative staging with 64-channel multidetector
      computed tomography. Two independent radiologists analyzed the images and
      classified the findings. Sensitivity, specificity, accuracy and overall accuracy
      were calculated for each observer. The interobserver agreement was also
      evaluated. RESULTS: The accuracy in the classification of categories T ranged
      from 74% to 96% for observer 1 and from 80% to 92% for observer 2. The overall
      accuracy was 70% for both observers. The weighted kappa index was 0.75,
      consistent with a significant interobserver agreement. The accuracy in the
      classification of lymph node involvement (category N) ranged from 55% to 79% for
      observer 1 and from 73% to 82% for observer 2. The evaluation of metastatic
      involvement showed an overall accuracy of 89.6% for both observers. CONCLUSION:
      64-channel multidetector computed tomography demonstrated clinically relevant
      accuracy in the preoperative staging of gastric adenocarcinoma as regards
      invasion depth (T category) and metastatic involvement (M category).

PMID- 25987748
TI  - Abdominal alterations in disseminated paracoccidioidomycosis: computed tomography
      findings.
AB  - OBJECTIVE: To evaluate the incidence and spectrum of abdominal computed
      tomography imaging findings in patients with paracoccidioidomycosis. MATERIALS
      AND METHODS: Retrospective analysis of abdominal computed tomography images of 26
      patients with disseminated paracoccidioidomycosis. RESULTS: Abnormal abdominal
      tomographic findings were observed in 18 patients (69.2%), while no significant
      finding was observed in the other 8 (30.8%) patients. CONCLUSION: Computed
      tomography has demonstrated to play a relevant role in the screening and
      detection of abdominal abnormalities in patients with disseminated
      paracoccidioidomycosis.

PMID- 25987749
TI  - Evolution of mammographic image quality in the state of Rio de Janeiro.
AB  - OBJECTIVE: To evaluate the evolution of mammographic image quality in the state
      of Rio de Janeiro on the basis of parameters measured and analyzed during health
      surveillance inspections in the period from 2006 to 2011. MATERIALS AND METHODS:
      Descriptive study analyzing parameters connected with imaging quality of 52
      mammography apparatuses inspected at least twice with a one-year interval.
      RESULTS: Amongst the 16 analyzed parameters, 7 presented more than 70% of
      conformity, namely: compression paddle pressure intensity (85.1%), films
      development (72.7%), film response (72.7%), low contrast fine detail (92.2%),
      tumor mass visualization (76.5%), absence of image artifacts (94.1%), mammography
      specific developers availability (88.2%). On the other hand, relevant parameters
      were below 50% conformity, namely: monthly image quality control testing (28.8%)
      and high contrast details with respect to microcalcifications visualization
      (47.1%). CONCLUSION: The analysis revealed critical situations in terms of
      compliance with the health surveillance standards. Priority should be given to
      those mammography apparatuses that remained non-compliant at the second
      inspection performed within the one-year interval.

PMID- 25987750
TI  - Susceptibility weighted imaging: differentiating between calcification and
      hemosiderin.
AB  - OBJECTIVE: To present a detailed explanation on the processing of magnetic
      susceptibility weighted imaging (SWI), demonstrating the effects of echo time and
      sensitive mask on the differentiation between calcification and hemosiderin.
      MATERIALS AND METHODS: Computed tomography and magnetic resonance (magnitude and
      phase) images of six patients (age range 41- 54 years; four men) were
      retrospectively selected. The SWI images processing was performed using the
      Matlab's own routine. RESULTS: Four out of the six patients showed calcifications
      at computed tomography images and their SWI images demonstrated hyperintense
      signal at the calcification regions. The other patients did not show any
      calcifications at computed tomography, and SWI revealed the presence of
      hemosiderin deposits with hypointense signal. CONCLUSION: The selection of echo
      time and of the mask may change all the information on SWI images, and compromise
      the diagnostic reliability. Amongst the possible masks, the authors highlight
      that the sigmoid mask allows for contrasting calcifications and hemosiderin on a
      single SWI image.

PMID- 25987751
TI  - An ABC for decision making.
AB  - The present study was aimed at proposing a systematic evaluation of cranial
      computed tomography, identifying the main aspects to be analyzed in order to
      facilitate the decision making process regarding diagnosis and management in
      emergency settings. The present descriptive study comprised a literature review
      at the following databases: Access Medicine and Access Emergency Medicine (McGraw
      Hill Education); British Medical Journal Evidence Center; UptoDate; Bireme;
      PubMed; Lilacs; SciELO; ProQuest; Micromedex (Thomson Reuters); Embase. Once the
      literature review was completed, the authors identified the main diseases with
      tomographic repercussions and proposed the present system to evaluate cranial
      computed tomography images. An easy-to-memorize ABC system will facilitate the
      decision making in emergency settings, as it covers the main diseases encountered
      by intensivists and emergency physicians, and provides a sequential guidance
      about anatomical structures to be investigated as well as their respective
      alterations. 

PMID- 25987753
TI  - Toxic and metabolic encephalopathies: iconographic essay.
AB  - Generally, toxic-metabolic diseases affecting the central nervous system can
      hardly be differentiated just on the basis of their clinical presentation.
      However, some typical neuroradiological features can guide the correct diagnosis.
      In this context, magnetic resonance imaging is an important tool which, in
      association with clinical and laboratory data, can establish an early and
      specific treatment. The present pictorial essay with selected cases from the
      archives of the authors' institution describes imaging findings which might help
      in the etiologic diagnosis of toxic-metabolic diseases. 

PMID- 25987752
TI  - Whole-body magnetic resonance imaging in children: state of the art.
AB  - Whole-body imaging in children was classically performed with radiography,
      positron-emission tomography, either combined or not with computed tomography,
      the latter with the disadvantage of exposure to ionizing radiation. Whole-body
      magnetic resonance imaging (MRI), in association with the recently developed
      metabolic and functional techniques such as diffusion-weighted imaging, has
      brought the advantage of a comprehensive evaluation of pediatric patients without
      the risks inherent to ionizing radiation usually present in other conventional
      imaging methods. It is a rapid and sensitive method, particularly in pediatrics,
      for detecting and monitoring multifocal lesions in the body as a whole. In
      pediatrics, it is utilized for both oncologic and non-oncologic indications such
      as screening and diagnosis of tumors in patients with genetic syndromes,
      evaluation of disease extent and staging, evaluation of therapeutic response and
      post-therapy follow-up, evaluation of non neoplastic diseases such as multifocal
      osteomyelitis, vascular malformations and syndromes affecting multiple regions of
      the body. The present review was aimed at describing the major indications of
      whole-body MRI in pediatrics added of technical considerations. 

PMID- 25987755
TI  - Biliary colon: an unusual case of intestinal obstruction.

PMID- 25987754
TI  - Intestinal and appendiceal paracoccidioidomycosis.

PMID- 25987756
TI  - Catamenial pneumothorax.

PMID- 25987757
TI  - Enhancing survival with early surgical resection of endobronchial metastasis in a
      follow-up of ovarian carcinoma.

PMID- 25987758
TI  - Current status of imaging diagnosis of musculoskeletal involvement in tropical
      diseases.

PMID- 25987759
TI  - Effects of adding local anesthetic and iodinated contrast agents to the
      paramagnetic contrast solution in direct MR arthrography.

PMID- 25987760
TI  - MDCT in the preoperative staging of gastric adenocarcinoma.

PMID- 25987762
TI  - Matched Gk -constructions always yield Ck -continuous isogeometric elements.
AB  - Gk (geometrically continuous surface) constructions were developed to create
      surfaces that are smooth also at irregular points where, in a quad-mesh, three or
      more than four elements come together. Isogeometric elements were developed to
      unify the representation of geometry and of engineering analysis. We show how
      matched Gk constructions for geometry and analysis automatically yield Ck
      isogeometric elements. This provides a formal framework for the existing and any
      future isogeometric elements based on geometric continuity.

PMID- 25987761
TI  - Which is your diagnosis?

PMID- 25987763
TI  - Shape matters: corolla curvature improves nectar discovery in the hawkmoth
      Manduca sexta.
AB  - 1. We measured the effects of variation in corolla curvature and nectary aperture
      radius on pollinator foraging ability using the hawkmoth Manduca sexta and 3D
      printed artificial flowers whose shapes were mathematically specified. 2. In
      dimorphic arrays containing trumpet-shaped flowers and flat-disk flowers,
      hawkmoths were able to empty the nectaries of significantly more trumpet-shaped
      flowers regardless of nectary aperture size. Interestingly, trumpet-shaped
      flowers needed to deviate only slightly from the flat-disk morphotype in order to
      significantly increase hawkmoth foraging ability. 3. Whole-flower three
      dimensional shape, particularly corolla curvature, has the potential to act as a
      mechanical guide for Manduca sexta, further implicating direct flower-proboscis
      contact as an important contributor to foraging success during flower handling in
      hawkmoths.

PMID- 25987764
TI  - Interaction pattern for the complex of B-DNA Fullerene compounds with a set of
      known replication proteins using docking study.
AB  - Fullerenes have attracted considerable attention due to their unique chemical
      structure and potential applications which has opened wide venues for possible
      human exposure to various fullerene types. Therefore, in depth knowledge of how
      fullerene may interfere with various cellular processes becomes quite imperative.
      The present study was designed to investigate how the presence of fullerene
      affect the binding of DNA with different enzymes involved in replication process.
      Different fullerenes were first docked with DNA and then binding scores of
      different enzymes was analyzed with fullerene docked DNA. C30, C40 & C50 once
      docked with DNA, reduced the binding score of primase, whereas no significant
      change in the binding score was observed with the helicase, ssb protein, dna pol
      delta, dna pol epsilon, ligase, DNA clamp, and topoisomerases. On the contrast,
      the binding score of RPA14 decreases in fluctuating manner while interacting with
      increasing molecular weight of fullerene bound single-stranded DNA complex. The
      study revealed the affect of fullerene family interacting with DNA on the binding
      pattern of enzymes involved in replication process. Study suggests that the
      presence of most of fullerenes may not affect the activity of these enzymes
      necessary for replication process whereas C30, C40 & C50 may disrupt the activity
      of primase, (strating point for DNA polymerase) its docking score decreases from
      13820 to 10702. 

PMID- 25987765
TI  - Mining, characterization and validation of EST derived microsatellites from the
      transcriptome database of Allium sativum L.
AB  - Expressed Sequence Tags (ESTs) with comprehensive transcript information are
      valuable resources for development of molecular markers as they are derived from
      conserved genic regions. The present study highlights the mining of EST database
      to deduce the class I hyper variable SSRs in A. sativum. From 21694 garlic EST
      sequences, 642 non-redundant SSRs were identified with an average frequency of 1
      per 14.9 kb of garlic transcriptome. The most abundant SSR motifs were the
      mononucleotides (32.86%) followed by trinucleotides (28.50%) and dinucleotides
      (13.39%). Among the individual SSRs, (A/T)n accounted for the highest number
      (137; 21.33%) followed by (G/C)n (74; 11.52%) and (AAG)n (63;9.81%). Primers
      designed from a robust set of 7 AsESTSSRs resulted in the amplification of 63
      polymorphic alleles in 14 accessions of garlic. The resolving power of the
      markers varied from 4.286 (AsSSR7) to 18.143 (AsSSR13) while the average marker
      index (MI) was 5.087. These EST-SSRs markers for garlic could be useful for the
      improvement of garlic linkage map and could be used for evaluating genetic
      variation and comparative genomics studies in Allium species. 

PMID- 25987766
TI  - MET inhibitors for treatment of advanced hepatocellular carcinoma: A review.
AB  - The current standard treatment option for advanced hepatocellular carcinoma (HCC)
      is sorafenib, but its clinical benefit is modest. In spite of many attempts, few
      drugs can provide any significant improvement of survival as the first- or second
      line therapy of choice in phase III randomized controlled trials. Recently, the
      subgroup analysis of a phase II randomized controlled trial has shown that
      tivantinib, a selective MET inhibitor, can significantly improve the overall
      survival in patients with MET-positive advanced HCC after the failure or
      intolerance of a prior systemic therapy. These findings enlighten the role of MET
      inhibitors in the treatment of advanced HCC. In this paper, we review all ongoing
      and completed clinical trials regarding this topic. As for the first-line therapy
      of advanced HCC, INC280 and foretinib are being evaluated in 2 phase II single
      arm trials; and MSC2156119J and golvatinib plus sorafenib are being compared with
      sorafenib alone in 2 phase II randomized controlled trials. As for the second
      line therapy of advanced HCC, tivantinib and cabozantinib are being compared with
      placebo in 2 phase III randomized controlled trials.

PMID- 25987768
TI  - Phycocyanobilin accelerates liver regeneration and reduces mortality rate in
      carbon tetrachloride-induced liver injury mice.
AB  - AIM: To investigate the hepatoprotective effects of phycocyanobilin (PCB) in
      reducing hepatic injury and accelerating hepatocyte proliferation following
      carbon tetrachloride (CCl4) treatment. METHODS: C57BL/6 mice were orally
      administered PCB 100 mg/kg for 4 d after CCl4 injection, and then the serum and
      liver tissue of the mice were collected at days 1, 2, 3, 5 and 7 after CCl4
      treatment. A series of evaluations were performed to identify the curative
      effects on liver injury and recovery. Aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), albumin and superoxide dismutase (SOD) were detected to
      indirectly assess the anti-inflammatory effects of PCB. Meanwhile, we detected
      the expressions of hepatocyte growth factor, transforming growth factor alpha
      (TGF-alpha), TGF-beta, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6), the factors which are associated with inflammation and liver
      regeneration. The protein expressions of proliferating cell nuclear antigen
      (PCNA), TNF-alpha and cytochrome C were detected by western blot. Furthermore,
      the survival rates were analyzed of mice which were administered a lethal dose of
      CCl4 (2.6 mg/kg) with or without PCB. RESULTS: In our research, PCB showed a
      strongly anti-inflammatory effect on CCl4-induced liver injury in mice. The ALT
      was significantly decreased after CCl4 treatment from day 1 (P < 0.01) and the
      AST was significantly decreased from day 2 (P < 0.001). Both albumin and liver
      SOD were increased from day 2 (P < 0.001 and P < 0.01), but serum SOD levels did
      not show a significant increase (P > 0.05). PCB protected the structure of liver
      from the injury by CCl4. TUNEL assay showed that PCB dramatically reduced the
      number of apoptotic cells after CCl4 treatment compared to the control (101.0 +/-
      25.4 vs 25.7 +/- 6.4, P < 0.01). The result of western blotting showed that PCB
      could increase PCNA expression, decrease TNF-alpha and cytochrome C expression.
      Furthermore, data shows that PCB could improve the survival rate of acute liver
      failure (ALF) mice which were injected with a lethal dose of CCl4 (60.0% vs
      20.0%). CONCLUSION: Our study indicated that PCB could be an ideal candidate for
      reversing acute liver injury or ALF.

PMID- 25987767
TI  - Downregulation of rho-associated protein kinase 1 by miR-124 in colorectal
      cancer.
AB  - AIM: To investigate the roles and interactions of rho-associated protein kinase
      (ROCK)1 and miR-124 in human colorectal cancer (CRC). METHODS: Expression of
      ROCK1 protein was examined by Western blotting, and quantitative reverse
      transcriptase PCR was performed to measure expression of ROCK1 mRNA and miR-124.
      Two cancer cell lines were transfected with pre-miR-124 (mimic) and anti-miR-124
      (inhibitor) and the effects on ROCK1 protein and mRNA expression were observed.
      In addition, cell proliferation was assessed via a 5-ethynyl-2' deoxyuridine
      assay. Soft agar formation assay, and cell migration and invasion assays were
      used to determine the effect of survivin on the transformation and invasion
      activity of CRC cells. RESULTS: miR-124 was significantly downregulated in CRC
      compared to normal specimens (0.603 +/- 0.092 vs 1.147 +/- 0.286, P = 0.016) and
      in metastatic compared to nonmetastatic CRC specimens (0.416 +/- 0.047 vs 0.696
      +/- 0.089, P = 0.020). Expression of miR-124 was significantly associated with
      CRC metastasis, tumor T and N stages, and tumor grade (all P < 0.05). ROCK1
      protein was significantly increased in CRC compared to normal tissues (1.896 +/-
      0.258 vs 0.866 +/- 0.136, P = 0.026), whereas ROCK1 mRNA expression was unaltered
      (2.613 +/- 0.251 vs 2.325 +/- 0.246). miR-124 and ROCK1 were inversely expressed
      in CRC tissues and cell lines. ROCK1 mRNA was unaltered in cells transfected with
      miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a
      significant reduction in ROCK1 protein in cells transfected with miR-124 mimic
      and a significant increase in cells transfected with miR-124 inhibitor (Ps <
      0.05). Transformation and invasion of cells transfected with miR-124 inhibitor
      were significantly increased compared to those in normal controls (P < 0.05).
      Cells transfected with miR-124 inhibitor showed increased cell proliferation.
      CONCLUSION: miR-124 promotes hyperplasia and contributes to invasion of CRC
      cells, but downregulates ROCK1. ROCK1 and miR-124 may play important roles in
      CRC.

PMID- 25987769
TI  - Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via
      JNK-dependent mechanism in mice.
AB  - AIM: To assess the effects of dihydromyricetin (DHM) as a hepatoprotective
      candidate in reducing hepatic injury and accelerating hepatocyte proliferation
      after carbon tetrachloride (CCl4) treatment. METHODS: C57 BL/6 mice were used in
      this study. Mice were orally administered with DHM (150 mg/kg) for 4 d after CCl4
      treatment. Serum and liver tissue samples were collected on days 1, 2, 3, 5 and 7
      after CCl4 treatment. The anti-inflammatory effect of DHM was assessed directly
      by hepatic histology detection and indirectly by serum levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), albumin, and superoxide
      dismutase (SOD). Inflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and
      tumor necrosis factor-alpha (TNF-alpha), were detected using ELISA kits.
      Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role
      of DHM in promoting hepatocyte proliferation. Hepatocyte apoptosis was measured
      by TUNEL assay. Furthermore, apoptosis proteins Caspases-3, 6, 8, and 9 were
      detected by Western blot. SP600125 were used to confirm whether DHM regulated
      liver regeneration through JNK/TNF-alpha pathways. RESULTS: DHM showed a strong
      anti-inflammatory effect on CCl4-induced liver injury in mice. DHM could
      significantly decrease serum ALT, AST, IL-1beta, IL-6 and TNF-alpha and increase
      serum albumin, SOD and liver SOD compared to the control group after CCl4
      treatment (P < 0.05). PCNA results indicated that DHM could significantly
      increase the number of PCNA positive cells compared to the control (348.9 +/-
      56.0 vs 107.1 +/- 31.4, P < 0.01). TUNEL assay showed that DHM dramatically
      reduced the number of apoptotic cells after CCl4 treatment compared to the
      control (365.4 +/- 99.4 vs 90.5 +/- 13.8, P < 0.01). Caspase activity detection
      showed that DHM could reduce the activities of Caspases- 8, 3, 6 and 9 compared
      to the control (P < 0.05). The results of Western blot showed that DHM increased
      the expression of JNK and decreased TNF-alpha expression. However, DHM could not
      affect TNF-alpha expression after SP600125 treatment. Furthermore, DHM could
      significantly improve the survival rate of acute liver failure (ALF) mice (73.3%
      vs 20.0%, P < 0.0001), and SP600125 could inhibit the effect of DHM. CONCLUSION:
      These findings demonstrate that DHM alleviates CCl4-induced liver injury,
      suggesting that DHM is a promising candidate for reversing liver injury and ALF.

PMID- 25987770
TI  - Hemodynamics and vasoactive substance levels during renal congestion that occurs
      in the anhepatic phase of liver transplantation.
AB  - AIM: To explore hemodynamics and vasoactive substance levels during renal vein
      congestion that occurs in the anhepatic phase of liver transplantation. METHODS:
      New Zealand rabbits received ligation of the hepatic pedicle, supra-hepatic vena
      cava and infra-hepatic vena cava [anhepatic phase group (APH); n = 8], the renal
      veins (RVL; n = 8), renal veins and hepatic pedicle [with the inferior vena cava
      left open) (RVHP; n = 8)], or a sham operation (SOP; n = 8). Hemodynamic
      parameters (systolic, diastolic, and mean arterial blood pressures) and the
      levels of serum bradykinin (BK) and angiotensin II (ANGII) were measured at
      baseline (0 min), and 10 min, 20 min, 30 min, and 45 min after the surgery.
      Correlation analyses were performed to evaluate the associations between
      hemodynamic parameters and levels of vasoactive substances. RESULTS: All
      experimental groups (APH, RVL, and RVHP) showed significant decreases in
      hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures)
      compared to baseline levels, as well as compared to the SOP controls (P < 0.05
      for all). In contrast, BK levels were significantly increased compared to
      baseline in the APH, RVL, and RVHP groups at all time points measured (P < 0.05
      for all), whereas no change was observed in the SOP controls. There were no
      significant differences among the experimental groups for any measure at any time
      point. Further analyses revealed that systolic, diastolic, and mean arterial
      blood pressures were all negatively correlated with BK levels, and positively
      correlated with ANGII levels in the APH, RVL, and RVHP groups (P < 0.05 for all).
      CONCLUSION: In the anhepatic phase of orthotopic liver transplantation, renal
      vein congestion significantly impacts hemodynamic parameters, which correlate
      with serum BK and ANGII levels.

PMID- 25987771
TI  - Pancreas-sparing duodenectomy with regional lymph node dissection for early-stage
      ampullary carcinoma: A case control study using propensity scoring methods.
AB  - AIM: To investigate the outcomes of pancreas-sparing duodenectomy (PSD) with
      regional lymph node dissection vs pancreaticoduodenectomy (PD). METHODS: Between
      August 2001 and June 2014, 228 patients with early-stage ampullary carcinoma (Amp
      Ca) underwent surgical treatment (PD, n = 159; PSD with regional lymph node
      dissection, n = 69). The patients were divided into two groups: the PD group and
      the PSD group. Propensity scoring methods were used to select patients with
      similar disease statuses. A total of 138 matched cases, with 69 patients in each
      group, were included in the final analysis. RESULTS: The median operative time
      was shorter among the patients in the PSD group (435 min) compared with those in
      the PD group (481 min, P = 0.048). The median blood loss in the PSD group was
      significantly less than that in the PD group. The median length of hospital stay
      was shorter for patients in the PSD group vs the PD group. The incidence of
      pancreatic fistula was higher among patients in the PD group vs the PSD group.
      The 1-, 3-, and 5-year overall survival and disease-free survival rates for
      patients in the PSD group were 83%, 70%, 44% and 73%, 61%, 39%, respectively, and
      these values were not different than compared with those in the PD group (P =
      0.625). CONCLUSION: PSD with regional lymph node dissection presents an
      acceptable morbidity in addition to its advantages over PD. PSD may be a safe and
      feasible alternative to PD in the treatment of early-stage Amp Ca.

PMID- 25987772
TI  - Relevance of low viral load in haemodialysed patients with chronic hepatitis C
      virus infection.
AB  - AIM: To identify predictors of sustained virological response in hemodialysed
      patients treated by PEGinterferon alpha for chronic hepatitis C, genotype 1.
      METHODS: The sustained virological response (SVR) rate, IL28B genotype, IFNL4
      genotype, initial viral load (IVL) and other pretreatment variables in 39 end
      stage renal disease patients (ESRD) on maintenance haemodialysis (HD) infected
      with hepatitis C virus (HCV), genotype 1b, were compared with a control group of
      109 patients with normal kidney function treated within the same period. All the
      patients were treatment naive and had well compensated liver disease. The ESRD
      patients received 135 MUg of PEGylated interferon alpha-2a (PegIFN-alpha) weekly
      and a reduced dose of ribavirin (RBV) was administered to 23/39 patients with an
      initial haemoglobin level > 10 g/dL. Control group patients were given standard
      doses of PegIFN-alpha and RBV. SVR was assessed as HCV RNA negativity 24 wk post
      treatment. A t-test or ANOVA were used for comparisons of the means and a chi(2)
      test compared the frequencies. Logistic regression was used to determine
      significant predictors of SVR. Cutoff values for continuous variables were
      obtained from Receiver Operating Characteristic analysis. RESULTS: The
      distribution of IL28B rs12979860 CC, CT and TT genotypes in the ESRD group was
      28.2%, 64.1% and 7.7%, respectively, and 19.3%, 62.4% and 18.3% in the controls.
      The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B. The
      proportion of patients with a low IVL (< 600000 IU/mL) was significantly higher
      in the ESRD group than in the controls (28/39, 71.8% vs 51/109, 46.8%, P =
      0.009), as was the proportion of patients with low IVL in IL28B CC carriers
      compared with non-CC carriers in the ESRD group (10/11, 90.9% vs 18/28, 64.3%, P
      = 0.0035). This difference was not found in the controls (7/22, 31.8% vs 44/87,
      50.6%, P = 0.9). The overall SVR rate was 64.1% (25/39) in the ESRD group and
      50.5% (55/109) in the control group (P = 0.19). 11/11 (100%) and 19/22 (86.4%)
      IL28B CC patients achieved SVR in the ESRD and control groups, respectively. A
      statistically significant association between SVR and IL28B and IFNL4 variants
      was found in both groups. The ESRD patients who achieved SVR showed the lowest
      IVL [median 21000, interquartile range (IQR): 6000-23000 IU/mL], compared with
      ESRD individuals without SVR (1680000, IQR: 481000-6880000, P = 0.001), controls
      with SVR (387000, IQR: 111000-1253000) and controls without SVR (905000, IQR:
      451000-3020000). In ESRD, an IVL < 600000 IU/mL was strongly associated with SVR:
      24/28 (85.7%) patients who achieved SVR had viraemia below this threshold.
      CONCLUSION: Haemodialysis decreases the viral load, especially in IL28B CC
      genotype carriers. A low IVL was the strongest predictor of SVR in ESRD patients
      identified in multivariate analysis.

PMID- 25987773
TI  - Long-term oncologic outcomes of laparoscopic vs open surgery for stages II and
      III rectal cancer: A retrospective cohort study.
AB  - AIM: To evaluate the 5-year survival after laparoscopic surgery vs open surgery
      for stages II and III rectal cancer. METHODS: This study enrolled 406 consecutive
      patients who underwent curative resection for stages II and III rectal cancer
      between January 2000 and December 2009 [laparoscopic rectal resection (LRR), n =
      152; open rectal resection (ORR), n = 254]. Clinical characteristics, operative
      outcomes, pathological outcomes, postoperative recovery, and 5-year survival
      outcomes were compared between the two groups. RESULTS: Most of the clinical
      characteristics were similar except age (59 years vs 55 years, P = 0.033) between
      the LRR group and ORR group. The proportion of anterior resection was higher in
      the LRR group than that in the ORR group (81.6% vs 66.1%, P = 0.001). The LRR
      group had less estimated blood loss (50 mL vs 200 mL, P < 0.001) and a lower rate
      of blood transfusion (4.6% vs 11.8%, P = 0.019) compared to the ORR group. The
      pathological outcomes of the two groups were comparable. The LRR group was
      associated with faster recovery of bowel function (2.8 d vs 3.7 d, P < 0.001) and
      shorter postoperative hospital stay (11.7 d vs 13.7 d, P < 0.001). The median
      follow-up time was 63 mo in the LRR group and 65 mo in the ORR group. As for the
      survival outcomes, the 5-year local recurrence rate (16.0% vs 16.4%, P = 0.753),
      5-year disease-free survival (DFS) rate (63.0% vs 63.1%, P = 0.589), and 5-year
      overall survival (OS) rate (68.1% vs 63.5%, P = 0.682) were comparable between
      the LRR group and the ORR group. Stage by stage, there were also no statistical
      differences between the LRR group and the ORR group in terms of the 5-year local
      recurrence rate (stage II: 6.3% vs 8.7%, P = 0.623; stage III: 26.4% vs 23.2%, P
      = 0.747), 5-year DFS rate (stage II: 77.5% vs 77.6%, P = 0.462; stage III: 46.5%
      vs 50.9%, P = 0.738), and 5-year OS rate (stage II: 81.4% vs 74.3%, P = 0.242;
      stage III: 53.9% vs 54.1%, P = 0.459). CONCLUSION: LRR for stages II and III
      rectal cancer can yield comparable long-term survival while achieving short-term
      benefits compared to open surgery.

PMID- 25987774
TI  - High-resolution microendoscopy for esophageal cancer screening in China: A cost
      effectiveness analysis.
AB  - AIM: To study the cost-effectiveness of high-resolution microendoscopy (HRME) in
      an esophageal squamous cell carcinoma (ESCC) screening program in China. METHODS:
      A decision analytic Markov model of ESCC was developed. Separate model analyses
      were conducted for cohorts consisting of an average-risk population or a high
      risk population in China. Hypothetical 50-year-old individuals were followed
      until age 80 or death. We compared three different strategies for both cohorts:
      (1) no screening; (2) standard endoscopic screening with Lugol's iodine staining;
      and (3) endoscopic screening with Lugol's iodine staining and an HRME. Model
      parameters were estimated from the literature as well as from GLOBOCAN, the
      Cancer Incidence and Mortality Worldwide cancer database. Health states in the
      model included non-neoplasia, mild dysplasia, moderate dysplasia, high-grade
      dysplasia, intramucosal carcinoma, operable cancer, inoperable cancer, and death.
      Separate ESCC incidence transition rates were generated for the average-risk and
      high-risk populations. Costs in Chinese currency were converted to international
      dollars (I$) and were adjusted to 2012 dollars using the Consumer Price Index.
      RESULTS: The main outcome measurements for this study were quality-adjusted life
      years (QALYs) and incremental cost-effectiveness ratio (ICER). For the average
      risk population, the HRME screening strategy produced 0.043 more QALYs than the
      no screening strategy at an additional cost of I$646, resulting in an ICER of
      I$11808 per QALY gained. Standard endoscopic screening was weakly dominated.
      Among the high-risk population, when the HRME screening strategy was compared
      with the standard screening strategy, the ICER was I$8173 per QALY. For both the
      high-risk and average-risk screening populations, the HRME screening strategy
      appeared to be the most cost-effective strategy, producing ICERs below the
      willingness-to-pay threshold, I$23500 per QALY. One-way sensitivity analysis
      showed that, for the average-risk population, higher specificity of Lugol's
      iodine (> 40%) and lower specificity of HRME (< 70%) could make Lugol's iodine
      screening cost-effective. For the high-risk population, the results of the model
      were not substantially affected by varying the follow-up rate after Lugol's
      iodine screening, Lugol's iodine test characteristics (sensitivity and
      specificity), or HRME specificity. CONCLUSION: The incorporation of HRME into an
      ESCC screening program could be cost-effective in China. Larger studies of HRME
      performance are needed to confirm these findings.

PMID- 25987775
TI  - Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic
      hepatitis B.
AB  - AIM: To compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) in
      Asian and non-Asian chronic hepatitis B (CHB) patients. METHODS: The efficacy and
      safety of the initial 48 wk of treatment with TDF was compared in a post-hoc
      analysis of combined data from 217 Asians and 299 non-Asians included in Studies
      102 and 103 and a post-approval, open-label trial (Study 123). Patient groups
      were compared according to baseline hepatitis B e antigen (HBeAg) status and
      viral load. The main outcome measures included the proportion of patients who
      achieved a hepatitis B virus (HBV) DNA level < 400 copies/mL at Week 48 of
      treatment. Secondary measures included: HBV DNA and alanine aminotransaminase
      (ALT) levels over time; proportion of patients with normal ALT levels; proportion
      of patients with HBeAg loss/seroconversion and proportion of patients with
      hepatitis B surface antigen loss/seroconversion; changes in liver histology.
      Safety and tolerability were evaluated by the occurrence of adverse events (AEs),
      serious AEs, laboratory abnormalities, discontinuation of the study drug due to
      AEs, or death. The primary efficacy and safety analysis set included all patients
      who were randomly assigned to treatment and received at least one dose of study
      drug. RESULTS: At week 48, similar proportions of Asians and non-Asians reached
      HBV DNA < 400 copies/mL (96% of Asian and 97% of non-Asian patients with HBeAg
      negative CHB and 83% of Asian and 79% of non-Asian patients with HBeAg-positive
      CHB had HBV DNA) and normal ALT (78% of Asian and 81% of non-Asian patients with
      HBeAg-negative CHB and 71% of Asian and 74% of non-Asian patients with HBeAg
      positive CHB had normal ALT). On-treatment HBV DNA decline rates were similar
      between Asians and non-Asians regardless of baseline HBeAg status and viral load.
      HBV DNA decline during the first four weeks was 2.9 log10 copies/mL in HBeAg
      negative Asians and non-Asians, and in HBeAg-positive non-Asians, and 3.1 log10
      copies/mL in HBeAg-positive Asians. HBeAg loss and seroconversion was achieved in
      14% of Asians vs 26% and 24%, respectively, in non-Asians. Liver histology
      improved in 77.2% of Asians and 71.5% of non-Asians. No resistance to TDF
      developed. No renal safety signals were observed. CONCLUSION: TDF demonstrated
      similar viral suppression, normalization of ALT, improvements in liver fibrosis,
      and no detectable resistance in Asian and non-Asian patients regardless of
      baseline HBeAg status.

PMID- 25987776
TI  - Psychosocial mechanisms for the transmission of somatic symptoms from parents to
      children.
AB  - AIM: To examine familial aggregation of irritable bowel syndrome (IBS) via
      parental reinforcement/modeling of symptoms, coping, psychological distress, and
      exposure to stress. METHODS: Mothers of children between the ages of 8 and 15
      years with and without IBS were identified through the Group Health Cooperative
      of Puget Sound. Mothers completed questionnaires, including the Child Behavior
      Checklist (child psychological distress), the Family Inventory of Life Events
      (family exposure to stress), SCL-90R (mother psychological distress), and the
      Pain Response Inventory (beliefs about pain). Children were interviewed
      separately from their parents and completed the Pain Beliefs Questionnaire
      (beliefs about pain), Pain Response Inventory (coping) and Child Symptom
      Checklist [gastrointestinal (GI) symptoms]. In addition, health care utilization
      data was obtained from the automated database of Group Health Cooperative.
      Mothers with IBS (n = 207) and their 296 children were compared to 240 control
      mothers and their 335 children, while controlling for age and education. RESULTS:
      Hypothesis 1: reinforcement of expression of GI problems is only related to GI
      symptoms, but not others (cold symptoms) in children. There was no significant
      correlation between parental reinforcement of symptoms and child expression of GI
      or other symptoms. Hypothesis 2: modeling of GI symptoms is related to GI but not
      non-GI symptom reporting in children. Children of parents with IBS reported more
      non-GI (8.97 vs 6.70, P < 0.01) as well as more GI (3.24 vs 2.27, P < 0.01)
      symptoms. Total health care visits made by the mother correlated with visits made
      by the child (rho = 0.35, P < 0.001 for cases, rho = 0.26, P < 0.001 for
      controls). Hypothesis 3: children learn to share the methods of coping with
      illness that their mothers exhibit. Methods used by children to cope with
      stomachaches differed from methods used by their mothers. Only 2/16 scales showed
      weak but significant correlations (stoicism rho = 0.13, P < 0.05; acceptance rho
      = 0.13, P < 0.05). Hypothesis 4: mothers and children share psychological traits
      such as anxiety, depression, and somatization. Child psychological distress
      correlated with mother's psychological distress (rho = 0.41, P < 0.001 for cases,
      rho= 0.38, P < 0.001 for controls). Hypothesis 5: stress that affects the whole
      family might explain the similarities between mothers and their children. Family
      exposure to stress was not a significant predictor of children's symptom reports.
      Hypothesis 6: the intergenerational transmission of GI illness behavior may be
      due to multiple mechanisms. Regression analysis identified multiple independent
      predictors of the child's GI complaints, which were similar to the predictors of
      the child's non-GI symptoms (mother's IBS status, child psychological symptoms,
      child catastrophizing, and child age). CONCLUSION: Multiple factors influence the
      reporting of children's gastrointestinal and non-gastrointestinal symptoms. The
      clustering of illness within families is best understood using a model that
      incorporates all these factors.

PMID- 25987777
TI  - Comparison of the diagnostic yield and outcomes between standard 8 h capsule
      endoscopy and the new 12 h capsule endoscopy for investigating small bowel
      pathology.
AB  - AIM: To evaluate the completion rate and diagnostic yield of the PillCam SB2-ex
      in comparison to the PillCam SB2. METHODS: Two hundred cases using the 8-h
      PillCam SB2 were retrospectively compared to 200 cases using the 12 h PillCam SB2
      ex at a tertiary academic center. Endoscopically placed capsules were excluded
      from the study. Demographic information, indications for capsule endoscopy,
      capsule type, study length, completion of exam, clinically significant findings,
      timestamp of most distant finding, and significant findings beyond 8 h were
      recorded. RESULTS: The 8 and 12 h capsule groups were well matched respectively
      for both age (70.90 +/- 14.19 vs 71.93 +/- 13.80, P = 0.46) and gender (45.5% vs
      48% male, P = 0.69). The most common indications for the procedure in both groups
      were anemia and obscure gastrointestinal bleeding. PillCam SB2-ex had a
      significantly higher completion rate than PillCam SB2 (88% vs 79.5%, P = 0.03).
      Overall, the diagnostic yield was greater for the 8 h capsule (48.5% for SB2 vs
      35% for SB2-ex, P = 0.01). In 4/70 (5.7%) of abnormal SB2-ex exams the clinically
      significant finding was noted in the small bowel beyond the 8 h mark. CONCLUSION:
      In our study, we found the PillCam SB2-ex to have a significantly increased
      completion rate, though without any improvement in diagnostic yield compared to
      the PillCam SB2.

PMID- 25987778
TI  - Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric
      micropapillary carcinomas.
AB  - AIM: To identify those with a micropapillary pattern, ascertain relative
      frequency and document clinicopathological characteristics by reviewing gastric
      carcinomas. METHODS: One hundred and fifty-one patients diagnosed with gastric
      cancer who underwent gastrectomy were retrospectively studied and the presence of
      a regional invasive micropapillary component was evaluated by light microscopy.
      All available hematoxylin-eosin (HE)-stained slides were histologically reviewed
      and 5 tumors were selected as putative micropapillary carcinoma when cancer cell
      clusters without a vascular core within empty lymphatic-like space comprised at
      least 5% of the tumor. Tumor tissues from these 5 invasive gastric carcinomas
      were immunostained using an anti-mucin 1 (MUC1) antibody (clone MA695) to detect
      the characteristic inside-out pattern and with D2-40 antibody to determine the
      presence of intratumoral lymph vessels. Detection of intraepithelial neutrophil
      apoptosis was evaluated in consecutive histological tissue sections by three
      independent methods, namely light microscopy with HE staining, the conventional
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling
      (TUNEL) method and immunohistochemistry for activated caspase-3 (clone C92-605).
      RESULTS: Among 151 gastric cancers resected for cure, 5 (3.3%) were
      adenocarcinomas with a micropapillary component. Four of the patients died of
      disease from 6 to 23 mo and one patient was alive with metastases at 9 mo. All
      patients had advanced-stage cancer (>= pT2) and lymph node metastasis. Positive
      MUC1 immunostaining on the stroma-facing surface (inside-out pattern) of the
      carcinomatous cluster cells, together with negative immunostaining for D2-40 in
      the cells limiting lymphatic-like spaces, confirmed the true micropapillary
      pattern in these gastric neoplasms. In all five cases, several micropapillae were
      infiltrated by neutrophils. HE staining, TUNEL assay and immunostaining for
      caspase-3 demonstrated apoptotic neutrophils within cytoplasmic vacuoles of tumor
      cells. These data suggest phagocytosis (cannibalism) of apoptotic neutrophils by
      micropapillary tumor cells. Tumor cell cannibalism is usually found in aggressive
      tumors with anaplastic morphology. Our data extend these observations to gastric
      micropapillary carcinoma: a tumor histotype analogously characterized by
      aggressive behavior and poor prognosis. The results are of interest because they
      raise the intriguing possibility that neutrophil cannibalism by tumor cells may
      be one of the mechanisms favoring tumor growth in gastric micropapillary
      carcinomas. CONCLUSION: This is the first study showing phagocytosis
      (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary
      carcinomas.

PMID- 25987779
TI  - Effectiveness of therapeutic barium enema for diverticular hemorrhage.
AB  - AIM: To evaluate the effectiveness of barium impaction therapy for patients with
      colonic diverticular bleeding. METHODS: We reviewed the clinical charts of
      patients in whom therapeutic barium enema was performed for the control of
      diverticular bleeding between August 2010 and March 2012 at Yokohama Rosai
      Hospital. Twenty patients were included in the review, consisting of 14 men and 6
      women. The median age of the patients was 73.5 years. The duration of the follow
      up period ranged from 1 to 19 mo (median: 9.8 mo). Among the 20 patients were 11
      patients who required the procedure for re-bleeding during hospitalization, 6
      patients who required it for re-bleeding that developed after the patient left
      the hospital, and 3 patients who required the procedure for the prevention of re
      bleeding. Barium (concentration: 150 w%/v%) was administered per the rectum, and
      the leading edge of the contrast medium was followed up to the cecum by
      fluoroscopy. After confirmation that the ascending colon and cecum were filled
      with barium, the enema tube was withdrawn, and the patient's position was changed
      every 20 min for 3 h. RESULTS: Twelve patients remained free of re-bleeding
      during the follow-up period (range: 1-19 mo) after the therapeutic barium enema,
      including 9 men and 3 women with a median age of 72.0 years. Re-bleeding occurred
      in 8 patients including 5 men and 3 women with a median age of 68.5 years: 4
      developed early re-bleeding, defined as re-bleeding that occurs within one week
      after the procedure, and the remaining 4 developed late re-bleeding. The DFI
      (disease-free interval) decreased 0.4 for 12 mo. Only one patient developed a
      complication from therapeutic barium enema (colonic perforation). CONCLUSION:
      Therapeutic barium enema is effective for the control of diverticular hemorrhage
      in cases where the active bleeding site cannot be identified by colonoscopy.

PMID- 25987780
TI  - Endoscopic and biopsy diagnoses of superficial, nonampullary, duodenal
      adenocarcinomas.
AB  - AIM: To investigate the accuracy of endoscopic or biopsy diagnoses of superficial
      nonampullary duodenal epithelial tumors (NADETs). METHODS: Clinicopathological
      data were reviewed for 84 superficial NADETs from 74 patients who underwent
      surgery or endoscopic resection between September 2002 and August 2014 at a
      single prefectural cancer center. Superficial NADETs were defined as lesions
      confined to the mucosa or submucosa. Demographic and clinicopathological data
      were retrieved from charts, endoscopic and pathologic reports. Endoscopic reports
      included endoscopic diagnosis, location, gross type, diameter, color, and
      presence or absence of biopsy. Endoscopic diagnoses were made by an endoscopist
      in charge of the examination before biopsy specimens were obtained. Endoscopic
      images were obtained using routine, front-view, high-resolution video endoscopy,
      and chromoendoscopy with indigocarmine was performed for all lesions. Endoscopic
      images were reviewed by at least two endoscopists to assess endoscopic findings
      indicative of carcinoma. Preoperative diagnoses based on endoscopy and biopsy
      findings were compared with histological diagnoses of resected specimens.
      Sensitivity, specificity, and accuracy were assessed for endoscopic diagnosis and
      biopsy diagnosis. RESULTS: The majority (81%) of the lesions were located in the
      second portion of the duodenum. The median lesion diameter was 14.5 mm according
      to final histology. Surgery was performed for 49 lesions from 39 patients, and 35
      lesions from 35 patients were endoscopically resected. Final histology confirmed
      65 carcinomas, 15 adenomas, and 3 hyperplasias. A final diagnosis of duodenal
      carcinoma was made for 91% (52/57) of the lesions diagnosed as carcinoma by
      endoscopy and 93% (42/45) of the lesions diagnosed as carcinoma by biopsy. The
      sensitivity, specificity, and accuracy of endoscopic diagnoses were 80%, 72%, and
      78%, respectively, whereas those of biopsy diagnoses were 72%, 80%, and 74%,
      respectively. Preoperative diagnoses of carcinomas were made in 88% (57/65) of
      the carcinoma lesions via endoscopy or biopsy. Endoscopic findings associated
      with carcinoma were red color, depression, and mixed-type morphology. CONCLUSION:
      Preoperative endoscopy and biopsy showed similar accuracies in the diagnosis of
      carcinoma in patients with superficial NADETs.

PMID- 25987781
TI  - Efficacy of 14-d vs 7-d moxifloxacin-based triple regimens for second-line
      Helicobacter pylori eradication.
AB  - AIM: To evaluate the efficacy of the 14-d moxifloxacin-based triple therapy for
      the second-line eradication of Helicobacter pylori (H. pylori) infection.
      METHODS: Between 2011 and 2013, we conducted a retrospective review of the
      medical records of 160 patients who had experienced failure of their first-line
      proton pump inhibitor-based eradication therapy and subsequently received the
      moxifloxacin-based triple therapy as a second-line eradication treatment regimen.
      The patients who were treated with the moxifloxacin-based triple therapy (oral 20
      mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.)
      for 7 d were assigned to the RAM-7 group (n = 79) while those who took them for
      14 days were assigned to RAM-14 group (n = 81). The eradication rates for both
      groups were determined by intention-to-treat (ITT) and per-protocol (PP)
      analyses. ITT analysis compared the treatment groups as originally allocated
      while the PP analysis including only those patients who had completed the
      treatment as originally allocated. Successful eradication therapy for H. pylori
      infection was defined as the documentation of a negative (13)C-urea breath test 4
      wk after the end of the eradication treatment. RESULTS: The overall ITT
      eradication rate was 76.2% (122/160). The final ITT eradication rates were 70.8%
      (56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4% (66/81; 95%CI: 74.6%
      88.3%) in the RAM-14 group (P = 0.034). The overall PP eradication rate was 84.1%
      (122/145), and the final PP eradication rates were 77.7% (56/72; 95%CI: 70.2%
      85.3%) in the RAM-7 group and 90.4% (66/73; 95%CI: 82.8%-98.1%) in the RAM-14
      group (P = 0.017). The H. pylori-eradication rates in the RAM-14 group were
      significantly higher compared with that of the RAM-7 group according to both the
      ITT (P = 0.034) and the PP analyses (P = 0.017). Both groups exhibited good
      treatment compliance (RAM-7/RAM-14 group: 100%/100%). The adverse event rates
      were 19.4% (14/72) and 20.5% (15/73) in the RAM-7 and RAM-14 groups, respectively
      (P = 0.441). Adverse events occurred in 14 of the 72 patients (19.4) in the RAM-7
      group and in 15 of the 73 patients (20.5) in the RAM-14 group. No statistically
      significant differences (P = 0.441) were observed. CONCLUSION: The 14-d
      moxifloxacin-based triple therapy is a significantly more effective second-line
      eradication treatment as compared to the 7-d alternative for H. pylori infection
      in South Korea.

PMID- 25987782
TI  - Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients
      with chronic hepatitis B?
AB  - AIM: To determine the association between the neutrophil to lymphocyte (N/L)
      ratio and the degree of liver fibrosis in patients with chronic hepatitis B (CHB)
      infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB
      patients who were admitted to the study hospitals for histological evaluation of
      chronic hepatitis B-related liver fibrosis were included in this retrospective
      study. The patients were divided into two groups based on the fibrosis score:
      individuals with a fibrosis score of F0 or F1 were included in the "no/minimal
      liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4
      were included in the "advanced liver fibrosis" group. The Statistical Package for
      Social Sciences 18.0 for Windows was used to analyze the data. A P value of <
      0.05 was accepted as statistically significant. RESULTS: Three experienced and
      blinded pathologists evaluated the fibrotic status and inflammatory activity of
      129 liver biopsy samples from the CHB patients. Following histopathological
      examination, the "no/minimal fibrosis" group included 79 individuals, while the
      "advanced fibrosis" group included 50 individuals. Mean (N/L) ratio levels were
      notably lower in patients with advanced fibrosis when compared with patients with
      no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet
      ratio index was markedly higher in cases with advanced fibrosis compared to those
      with no/minimal fibrosis. CONCLUSION: Reduced levels of the peripheral blood N/L
      ratio were found to give high sensitivity, specificity and predictive values in
      CHB patients with significant fibrosis. The prominent finding of our research
      suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis
      in patients with CHB.

PMID- 25987783
TI  - Inflammation scores predict survival for hepatitis B virus-related hepatocellular
      carcinoma patients after transarterial chemoembolization.
AB  - AIM: To compare the prognostic ability of inflammation scores for patients with
      hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) undergoing
      transarterial chemoembolization (TACE). METHODS: Data of 224 consecutive patients
      who underwent TACE for unresectable HBV-related HCC from September 2009 to
      November 2011 were retrieved from a prospective database. The association of
      inflammation scores with clinicopathologic variables and overall survival (OS)
      were analyzed, and receiver operating characteristic curves were generated, and
      the area under the curve (AUC) was calculated to evaluate the discriminatory
      ability of each inflammation score and staging system, including tumor-node
      metastasis, Barcelona Clinic Liver Cancer, and Cancer of the Liver Italian
      Program (CLIP) scores. RESULTS: The median follow-up period was 390 d, the one-,
      two-, and three-year OS were 38.4%, 18.3%, and 11.1%, respectively, and the
      median OS was 390 d. The Glasgow Prognostic Score (GPS), modifed GPS, neutrophil
      lymphocyte ratio, and Prognostic Index were associated with OS. The GPS
      consistently had a higher AUC value at 6 mo (0.702), 12 mo (0.676), and 24 mo
      (0.687) in comparison with other inflammation scores. CLIP consistently had a
      higher AUC value at 6 mo (0.656), 12 mo (0.711), and 24 mo (0.721) in comparison
      with tumor-node-metastasis and Barcelona Clinic Liver Cancer staging systems.
      Multivariate analysis revealed that alanine aminotransferase, GPS, and CLIP were
      independent prognostic factors for OS. The combination of GPS and CLIP (AUC =
      0.777) was superior to CLIP or GPS alone in prognostic ability for OS.
      CONCLUSION: The prognostic ability of GPS is superior to other inflammation
      scores for HCC patients undergoing TACE. Combining GPS and CLIP improved the
      prognostic power for OS.

PMID- 25987784
TI  - Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous
      cell carcinoma.
AB  - AIM: To determine the prognostic significance of preoperative serum neutrophil
      lymphocyte ratio (NLR) in esophageal squamous cell carcinoma (ESCC). METHODS:
      Data from 371 eligible patients with ESCC who had undergone surgery with curative
      intent at our institution between October 2000 and May 2007 were retrospectively
      recruited for analysis. The cutoff value of NLR was 3.0 as determined by the
      receiver operating characteristic curve, which discriminated between survival and
      death; the area under the curve was 0.709, and the sensitivity and specificity
      were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between
      the NLR and clinicopathological characteristics was analyzed using a chi(2) test.
      The prognostic influence of the NLR and other clinicopathological factors on
      cancer-specific survival (CSS) and recurrence-free survival (RFS) was studied
      using the Kaplan-Meier method. To evaluate the independent prognostic value of
      NLR, multivariate Cox regression models were applied. RESULTS: The median age of
      the patients was 57.0 years, and 276/371 (74.4%) patients were male. The NLR was
      <= 3.0 in 80.1% (297/371) of the patients, and the remaining 19.9% (74/371) had
      an NLR > 3.0. Median postoperative follow-up was 66.0 mo [interquartile range
      (IQR): 49.0-76.0 mo], with a follow-up rate of 94%. Follow-up was not
      significantly different between patients with an NLR <= and > 3.0 (63.13 +/- 1.64
      vs 61.52 +/- 3.66, P = 0.711). However, higher preoperative serum NLR was
      associated with significantly increased risks of higher pathological tumor status
      (P = 0.007). A significant, independent association between high preoperative
      serum NLR and poor clinical outcome was identified in a multivariate analysis for
      CSS (HR = 1.591; P = 0.007) and RFS (HR = 1.525; P = 0.013). Moreover, when
      patients were stratified by pathological tumor-node-metastasis (TNM) staging, the
      adverse effects of preoperative serum NLR on CSS (HR = 2.294; P = 0.008) and RFS
      (HR = 2.273; P = 0.008) were greatest in those patients with stage IIIA disease.
      CONCLUSION: Preoperative serum NLR is a useful prognostic marker to complement
      TNM staging for operable ESCC patients, particularly in patients with stage IIIA
      disease.

PMID- 25987785
TI  - Poor oncologic outcomes of hepatocellular carcinoma patients with intra-abdominal
      infection after hepatectomy.
AB  - AIM: To evaluate the impact of postoperative infectious complications on
      hepatocellular carcinoma following curative hepatectomy. METHODS: We performed a
      retrospective analysis of 200 hepatocellular carcinoma patients who underwent
      hepatectomy at our institution between September 2003 and June 2011. The
      patients' demographics, clinicopathological characteristics and postoperative
      infectious complications were analyzed. The Clavien-Dindo classification was
      adopted to assess the severity of complications. The dynamic change in the
      neutrophil-to-lymphocyte ratio, defined as the absolute neutrophil count divided
      by the absolute lymphocyte count, after surgery was also investigated. The
      observation endpoints for this study were recurrence-free survival and overall
      survival of the patients. Statistical analysis of the survival curves was
      performed using the Kaplan-Meier method and the log-rank test. The prognostic
      value of each variable for predicting prognosis was assessed via multivariate Cox
      proportional hazards regression analysis. The cutoff score for each variable was
      selected based on receiver operating characteristic curve analysis. All
      statistical tests were two-sided, and significance was set at P < 0.05. RESULTS:
      The median age of the patients was 49 years, and the majority of patients were
      male (86%) and had been infected with hepatitis B virus (86%). The 30-d
      postoperative infectious complication rate was 34.0% (n = 68). Kaplan-Meier
      survival analysis revealed that postoperative infection was significantly
      correlated with tumor recurrence (P < 0.001). The postoperative intra-abdominal
      infection group exhibited a worse prognosis than the non-intra-abdominal
      infection group (P < 0.001). A significantly increased incidence of postoperative
      intra-abdominal infection was observed in the patients with hepatic cirrhosis (P
      = 0.028), concomitant splenectomy (P = 0.007) or vascular invasion (P = 0.026).
      The patients who had an elevated postoperative neutrophil-to-lymphocyte ratio
      change (> 1.643) clearly exhibited poorer recurrence-free survival than those who
      did not (P = 0.009), although no significant correlation was observed between
      overall survival and the change in the postoperative neutrophil-to-lymphocyte
      ratio. Based on multivariate analysis, hepatitis B surface antigen positivity,
      Child-Turcotte-Pugh class B, an elevated postoperative neutrophil-to-lymphocyte
      ratio change and intra-abdominal infection were significant predictors of poor
      recurrence-free survival. Hepatic cirrhosis, the maximal tumor diameter and intra
      abdominal infection were significant predictors of overall survival. CONCLUSION:
      Postoperative intra-abdominal infection adversely affected oncologic outcomes,
      and the change in postoperative neutrophil-to-lymphocyte ratio was a good
      indicator of tumor recurrence in hepatocellular carcinoma patients after curative
      hepatectomy.

PMID- 25987787
TI  - Effect of peroral esophageal myotomy for achalasia treatment: A Chinese study.
AB  - AIM: To assess the safety and feasibility of peroral esophageal myotomy (POEM) in
      patients with achalasia. METHODS: From January 2012 to March 2014, 50 patients
      (28 men, 22 women; mean age: 42.8 years, range: 14-70 years) underwent POEM. Pre-
      and postoperative symptoms were quantified using the Eckardt scoring system.
      Barium swallow and esophagogastroscopy were performed before and after POEM,
      respectively. Esophageal motility was evaluated in all patients, both
      preoperatively and one month after POEM treatment, using a high-resolution
      manometry system. Manometry data, Eckardt scores, lower esophageal sphincter
      pressure and barium swallow results were used to evaluate the effect of the
      procedure. RESULTS: POEM was successfully completed for all patients. The mean
      procedure time was 55.4 +/- 17.3 min and the mean total length of myotomy of the
      circular esophagus was 10.5 +/- 2.6 cm. No specific complications occurred, with
      the exception of two patients that developed asymptomatic pneumomediastinum and
      subcutaneous emphysema. Clinical improvement in symptoms was achieved in all
      patients. Approximately 77.5% of patients experienced weight gain 6 mo after
      POEM, with an average of 4.78 kg (range: 2-15 kg). The lower esophageal sphincter
      resting pressure, four second integrated relaxation pressure and Eckardt scores
      were all significantly reduced after POEM (Ps < 0.05). A small segment of
      proximal esophageal peristalsis appeared postoperatively in two patients, but
      without normal esophageal peristalsis. The average diameter of the esophageal
      lumen decreased significantly from 4.39 to 3.09 cm (P < 0.01). CONCLUSION: POEM
      can relieve achalasia symptoms, improve gastroesophageal junction relaxation and
      restore esophageal body motility function, but not normal esophageal peristalsis.

PMID- 25987786
TI  - Significance of platelet count and platelet-based models for hepatocellular
      carcinoma recurrence.
AB  - AIM: To explore the effects of platelet count (PLT) and 11 platelet-based indices
      on postoperative recurrence of hepatocellular carcinoma (HCC). METHODS: We
      retrospectively analyzed 172 HCC patients who were treated by partial
      hepatectomy. Preoperative data, including laboratory biochemical results, were
      used to calculate the 11 indices included in the analysis. We performed receiver
      operating characteristic curve analysis to determine the optimal cut-off values
      for predicting recurrence. Cumulative rates of HCC recurrence were calculated
      using Kaplan-Meier survival curves and differences were analyzed by log-rank
      tests. Multivariate analyses were performed to identify independent predictors of
      recurrence, early recurrence (within one year after surgery), and late recurrence
      in HCC. To obtain better prognostic models, PLT-based indices were analyzed
      separately after being expressed as binary and continuous variables. Two platelet
      unrelated, validated HCC prognostic models were included in the analyses as
      reference indices. Additional analyses were performed after patients were
      stratified based on hepatitis B virus infection status, cirrhosis, and tumor size
      to investigate the significance of platelets in different subgroups. RESULTS: In
      the study cohort, 44.2% (76/172) of patients experienced HCC recurrence, and
      50.6% (87/172) died during a median follow-up time of 46 mo. PLT and five of the
      11 platelet-related models were significant predisposing factors for recurrence
      (P < 0.05). Multivariate analysis indicated that, among the clinical parameters,
      presence of ascites, PLT >= 148 * 10(9)/L, alkaline phosphatase >= 116 U/L, and
      tumor size >= 5 cm were independently associated with a higher risk of HCC
      recurrence (P < 0.05). Independent and significant models included the aspartate
      aminotransferase/PLT index, fibrosis index based on the four factors, fibro
      quotient, aspartate aminotransferase/PLT/gamma-glutamyl transpeptidase/alpha
      fetoprotein index, and the PLT/age/alkaline phosphatase/alpha
      fetoprotein/aspartate aminotransferase index. There were different risk factors
      between early and late recurrences, and PLT and these indices were more inclined
      to influence late recurrence. PLT was only predictive of recurrence in non
      cirrhotic HCC patients, and was not influenced by tumor size, which was a
      critical confounder in our study. CONCLUSION: PLT and PLT-based noninvasive
      models are effective tools for predicting postoperative recurrence, especially
      late recurrence. Larger cohorts are needed to validate our findings.

PMID- 25987788
TI  - Diagnosis and surgical treatment of esophageal gastrointestinal stromal tumors.
AB  - AIM: To retrospectively evaluate our experience with the diagnosis and surgical
      resection of esophageal gastrointestinal stromal tumors (GISTs). METHODS: Between
      January 2003 and August 2014, five esophageal GIST cases were admitted to our
      hospital. In this study, the hospital records, surgery outcomes, tumor recurrence
      and survival of these patients were retrospectively reviewed. RESULTS: The median
      age of the patients was 45.6 years (range: 12-62 years). Three patients presented
      with dysphagia, and one patient presented with chest discomfort. The remaining
      patient was asymptomatic. Four patients were diagnosed with esophageal GISTs by a
      preoperative endoscopic biopsy. Three patients underwent esophagectomy, and two
      patients underwent video-assisted thoracoscopic surgery. The mean operating time
      was 116 min (range: 95-148 min), and the mean blood loss was 176 mL (range: 30
      300 mL). All tumors were completely resected. The mean length of postoperative
      hospital stay was 8.4 d (range: 6-12 d). All patients recovered and were
      discharged successfully. The median postoperative follow-up duration was 48 mo
      (range: 29-72 mo). One patient was diagnosed with recurrence, one patient was
      lost to follow-up, and three patients were asymptomatic and are currently being
      managed with close radiologic and clinical follow-up. CONCLUSION: Surgery is the
      standard, effective and successful treatment for esophageal GISTs. Long-term
      follow-up is required to monitor recurrence and metastasis.

PMID- 25987789
TI  - Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated
      channel 3 in Hirschsprung's disease.
AB  - AIM: To determine if hyperpolarisation-activated nucleotide-gated (HCN) channels
      exist in human colon, and to investigate the expression of HCN channels in
      Hirschsprung's disease. METHODS: We investigated HCN1, HCN2, HCN3 and HCN4
      protein expression in pull-through specimens from patients with Hirschsprung's
      disease (HSCR, n = 10) using the proximal-most ganglionic segment and distal-most
      aganglionic segment, as well as in healthy control specimens obtained at the time
      of sigmoid colostomy closure in children who had undergone anorectoplasty for
      imperforate anus (n = 10). Fluorescent immunohistochemistry was performed to
      assess protein distribution, which was then visualized using confocal microscopy.
      RESULTS: No HCN1 channel expression was observed in any of the tissues studied.
      Both HCN2 and HCN4 proteins were found to be equally expressed in the aganglionic
      and ganglionic bowel in HSCR and controls. HCN3 channel expression was found to
      be markedly decreased in the aganglionic colon vs ganglionic colon and controls.
      HCN2-4 channels were seen to be expressed within neurons of the myenteric and
      submucosal plexus of the ganglionic bowel and normal controls, and also co
      localised to interstitial cells of Cajal in all tissues studied. CONCLUSION: We
      demonstrate HCN channel expression in human colon for the first time. Reduced
      HCN3 expression in aganglionic bowel suggests its potential role in HSCR
      pathophysiology.

PMID- 25987790
TI  - Association of erectile dysfunction with depression in patients with chronic
      viral hepatitis.
AB  - AIM: To investigate the prevalence of erectile dysfunction (ED) and its
      association with depression in patients with chronic viral hepatitis. METHODS:
      This single center cross-sectional study was conducted from August 2013 through
      January 2014. All outpatients with chronic viral hepatitis in our liver clinic
      between 18 and 80 years of age were considered eligible for this study. The
      exclusion criteria included well-established causes of ED, such as diabetes,
      hypertension, hyperlipidemia, alcohol abuse, liver cirrhosis, ischemic heart
      disease, renal disease, neurologic disease, and malignancy. We also excluded the
      patients who had incompletely answered the questionnaires. ED was assessed using
      the validated Korean version of the International Index of Erectile Function
      (IIEF-5) scale. The Korean version of the self-administered Beck Depression
      Inventory (BDI) scale was used to assess depression in the patients. Demographic
      and medical data were obtained from the patients' medical records. Current or
      past history of psychiatric diagnosis and drug history including the use of an
      antiviral agent and an antidepressant were also recorded. RESULTS: A total of 727
      patients met the initial eligibility criteria. Six hundred seventeen patients
      were excluded because their medical records contained one or more of the
      previously determined exclusion criteria. The remaining 110 patients were
      assessed based on the BDI and IIEF-5 questionnaires. Based on the IIEF-5 scale,
      the prevalence of ED among patients with chronic viral hepatitis was 40%.
      Compared with the non-ED group, patients in the ED group were older. The
      proportion of patients in the ED group who had a job or who were naive peg
      interferon users was lower than that in patients in the non-ED group. Patients
      with ED had significantly lower scores on the IIEF-5 scale than patients without
      ED (11.75 +/- 4.88 vs 21.33 +/- 1.86, P = 0.000). Patients with ED rated
      significantly higher scores on the BDI scale compared with patients without ED
      (12.59 +/- 7.08 vs 5.30 +/- 4.00, P = 0.000). Also, the IIEF-5 scores were
      negatively correlated with age, employment, and BDI scores. In the multiple
      logistic regression analysis, age and depression were independently associated
      with erectile dysfunction (P = 0.019 and 0.000, respectively). CONCLUSION:
      Patients with chronic viral hepatitis have a high prevalence of ED. Age and
      depression are independent factors for ED in male patients with chronic viral
      hepatitis.

PMID- 25987791
TI  - Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C
      virus infection: ANRS-HC25-VITAVIC study.
AB  - AIM: To investigate if correction of hypovitaminosis D before initiation of Peg
      interferon-alpha/ribavirin (PegIFN/RBV) therapy could improve the efficacy of
      PegIFN/RBV in previously null-responder patients with chronic genotype 1 or 4
      hepatitis C virus (HCV) infection. METHODS: Genotype 1 or 4 HCV-infected patients
      with null response to previous PegIFN/RBV treatment and with hypovitaminosis D (<
      30 ng/mL) prospectively received cholecalciferol 100000 IU per week for 4 wk
      [from week -4 (W-4) to W0], followed by 100000 IU per month in combination with
      PegIFN/RBV for 12 mo (from W0 to W48). The primary outcome was the rate of early
      virological response defined by an HCV RNA < 12 IU/mL after 12 wk PegIFN/RBV
      treatment. RESULTS: A total of 32 patients were included, 19 (59%) and 13 (41%)
      patients were HCV genotype 1 and 4, respectively. The median baseline vitamin D
      level was 15 ng/mL (range: 7-28). In modified intention-to-treat analysis, 29
      patients who received at least one dose of PegIFN/RBV were included in the
      analysis. All patients except one normalized their vitamin D serum levels. The
      rate of early virologic response was 0/29 (0%). The rate of HCV RNA < 12 IU/mL
      after 24 wk of PegIFN/RBV was 1/27 (4%). The safety profile was favorable.
      CONCLUSION: Addition of vitamin D to PegIFN/RBV does not improve the rate of
      early virologic response in previously null-responders with chronic genotype 1 or
      4 HCV infection.

PMID- 25987792
TI  - Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic
      Liver Cancer staging.
AB  - AIM: To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona
      Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival.
      METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child
      Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the
      largest nodule were determined at diagnosis for 1060 patients with hepatocellular
      carcinoma at a tertiary referral center for liver disease in Egypt. Demographic
      information, etiology of liver disease, and biochemical data (including serum
      bilirubin, albumin, international normalized ratio, alanine and aspartate
      aminotransferases, and AFP) were evaluated. Staging of the tumor was determined
      at the time of diagnosis using the BCLC staging system; 496 patients were stage A
      and 564 patients were stage B. Patients with mild ascites on initial ultrasound,
      computed tomography, or clinical examination, and who had a CTP score <= 9 were
      included in this analysis. All patients received therapy according to the
      recommended treatment based on the BCLC stage, and were monitored from the time
      of diagnosis to the date of death or date of data collection. The effect of the
      presence of ascites and AFP level on survival was analyzed. RESULTS: At the time
      the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC
      stages A and B, respectively, had died. Overall mean survival of the BCLC A and B
      patients during a three-year follow-up period was 31 mo [95% confidence interval
      (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of
      ascites, multiple focal lesions, large tumor size, AFP level and CTP score were
      independent predictors of survival for the included patients on multivariate
      analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP >= 200
      ng/mL, and 8% had both. Their median survival in the presence of ascites was
      shorter if AFP was >= 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites,
      patients with AFP >= 200 ng/mL had a shorter survival (28 mo vs 39 mo). For stage
      B patients, survival for the corresponding groups was 12, 18, 19 and 22 mo. The
      one-, two-, and three-year survival rates for stage A patients without ascites
      and AFP < 200 ng/mL were 94%, 77%, and 71%, respectively, and for patients with
      ascites and AFP >= 200 ng/mL were 83%, 24%, and 22%, respectively (P < 0.001).
      Adding ascites and AFP >= 200 ng/mL improved the discriminatory ability for
      predicting prognosis (area under the curve, 0.618 vs 0.579 for BCLC, P < 0.001).
      CONCLUSION: Adding AFP and ascites to the BCLC staging classification can improve
      prognosis prediction for early and intermediate stages of hepatocellular
      carcinoma.

PMID- 25987793
TI  - Association of Streptococcus bovis presence in colonic content with advanced
      colonic lesion.
AB  - AIM: To prospectively examine the association between presence of Streptococcus
      bovis (S. bovis) in colonic suction fluid and the endoscopic findings on
      colonoscopy. METHODS: From May 2012 to March 2013, 203 consecutive patients who
      underwent colonoscopy for any reason were enrolled in the study. Exclusion
      criteria included: antibiotic use in the previous month, age younger than 18
      years, and inadequate preparation for colonoscopy. The colonoscopy was performed
      for the total length of the colon or to the occluding tumor. The endoscopic
      findings were registered. Samples were obtained proximal to the colonoscopic part
      of the suction tube from each patient and sent to the clinical microbiology
      laboratory for isolation and identification of S. bovis. Samples were incubated
      in enrichment media with addition of antibiotic disks for inhibition of growth of
      Gram-negative rods. The samples were seeded on differential growth media;
      suspected positive colonies were isolated and identified with Gram staining,
      catalase, and pyrrolidonyl arylamidase tests, and further identified using a
      VITEK2 system. Statistical analyses were performed using the Student's t and
      chi(2) tests. RESULTS: Of the 203 patients recruited, 49 (24%) patients were
      found to be S. bovis carriers; of them, the endoscopic findings included: 17
      (34.7%) cases with malignant tumors, 11 (22.4%) with large polyps, 5 (10.2%) with
      medium-sized polyps, 6 (12.2%) with small polyps, 4 (8.1%) with colitis, and 6
      (12.2%) normal colonoscopies. Of 154 patients found negative for S. bovis, the
      endoscopic findings included: none with malignant tumors, 9 (5.8%) cases with
      large polyps, 11 (7.1%) with medium-sized polyps, 26 (16.9%) with small polyps, 7
      (4.5%) with colitis, and 101 (65.6%) normal colonoscopies. S. bovis (Gram
      positive coccus) is considered part of the normal intestinal flora. There is an
      association between S. bovis bacteremia and colonic neoplasia. It is not well
      understood whether the bacterium has a pathogenetic role in the development of
      neoplasia or constitutes an epiphenomenon of colorectal neoplasms. There was a
      clear relationship between positivity for S. bovis in colonic suction fluid and
      findings of malignant tumors and large polyps in the colon. CONCLUSION: There is
      an association between S. bovis bacteremia and malignant colonic lesions; this
      should prompt for development of a reliable screening method for advanced colonic
      lesions.

PMID- 25987795
TI  - Self-reported dietary fructose intolerance in irritable bowel syndrome: Proposed
      diagnostic criteria.
AB  - AIM: To study the criteria for self-reported dietary fructose intolerance (DFI)
      and to evaluate subjective global assessment (SGA) as outcome measure. METHODS:
      Irritable bowel syndrome (IBS) patients were randomized in an open study design
      with a 2 wk run-in on a habitual IBS diet, followed by 12 wk with/without
      additional fructose-reduced diet (FRD). Daily registrations of stool frequency
      and consistency, and symptoms on a visual analog scale (VAS) were performed
      during the first 4 wk. SGA was used for weekly registrations during the whole
      study period. Provocation with high-fructose diet was done at the end of the
      registration period. Fructose breath tests (FBTs) were performed. A total of 182
      subjects performed the study according to the protocol (88 FRD, 94 controls).
      RESULTS: We propose a new clinically feasible diagnostic standard for self
      reported fructose intolerance. The instrument is based on VAS registrations of
      symptom relief on FRD combined with symptom aggravation upon provocation with
      fructose-rich diet. Using these criteria 43 of 77 patients (56%) in the present
      cohort of IBS patients had self-reported DFI. To improve the concept for clinical
      evaluation, we translated the SGA scale instrument to Norwegian and validated it
      in the context of the IBS diet regimen. The validation procedures showed a
      sensitivity, specificity and kappa value for SGA detecting the self-reported DFI
      group by FRD response within the IBS patients of 0.79, 0.75 and 0.53,
      respectively. Addition of the provocation test yielded values of 0.84, 0.76 and
      0.61, respectively. The corresponding validation results for FBT were 0.57, 0.34
      and -0.13, respectively. CONCLUSION: FRD improves symptoms in a subgroup of IBS
      patients. A diet trial followed by a provocation test evaluated by SGA can
      identify most responders to FRD.

PMID- 25987794
TI  - Models for predicting hepatitis B e antigen seroconversion in response to
      interferon-alpha in chronic hepatitis B patients.
AB  - AIM: To develop models to predict hepatitis B e antigen (HBeAg) seroconversion in
      response to interferon (IFN)-alpha treatment in chronic hepatitis B patients.
      METHODS: We enrolled 147 treatment-naive HBeAg-positive chronic hepatitis B
      patients in China and analyzed variables after initiating IFN-alpha1b treatment.
      Patients were tested for serum alanine aminotransferase (ALT), hepatitis B virus
      DNA, hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface
      antigen, HBeAg, antibody to hepatitis B e antigen (anti-HBe), and antibody to
      hepatitis B core antigen (anti-HBc) at baseline and 12 wk, 24 wk, and 52 wk after
      initiating treatment. We performed univariate analysis to identify response
      predictors among the variables. Multivariate models to predict treatment response
      were constructed at baseline, 12 wk, and 24 wk. RESULTS: At baseline, the 3
      factors correlating most with HBeAg seroconversion were serum ALT level > 4 * the
      upper limit of normal (ULN), HBeAg <= 500 S/CO, and anti-HBc > 11.4 S/CO. At 12
      wk, the 3 factors most associated with HBeAg seroconversion were HBeAg level <=
      250 S/CO, decline in HBeAg > 1 log10 S/CO, and anti-HBc > 11.8 S/CO. At 24 wk,
      the 3 factors most associated with HBeAg seroconversion were HBeAg level <= 5
      S/CO, anti-HBc > 11.4 S/CO, and decline in HBeAg > 2 log10 S/CO. Each variable
      was assigned a score of 1, a score of 0 was given if patients did not have any of
      the 3 variables. The 3 factors most strongly correlating with HBeAg
      seroconversion at each time point were used to build models to predict the
      outcome after IFN-alpha treatment. When the score was 3, the response rates at
      the 3 time points were 57.7%, 83.3%, and 84.0%, respectively. When the score was
      0, the response rates were 2.9%, 0.0%, and 2.1%, respectively. CONCLUSION: Models
      with good negative and positive predictive values were developed to calculate the
      probability of response to IFN-alpha therapy.

PMID- 25987796
TI  - Oral mixture of autologous colon-extracted proteins for the Crohn's disease: A
      double-blind trial.
AB  - AIM: To evaluate the safety and efficacy of oral administration of AlequelTM, an
      autologous protein-containing colon extract. METHODS: A total of 43 patients were
      enrolled in a randomized, placebo-controlled, double-blind trial. Patients were
      orally administered with autologous protein-containing colon extract three doses
      of autologous study drug per week for 15 wk, for a total of 45 doses. Patients
      were followed for safety parameters. Remission was defined as a Crohn's disease
      activity index (CDAI) score of less than or equal to 150. All patients were
      followed for changes in subsets of T cells by fluorescence-activated cell sorting
      analysis. RESULTS: Analysis was performed on a total number of evaluable patients
      of 14 in the study drug group and 15 in the placebo group. Treatment was well
      tolerated by all patients. No major treatment-related adverse events were
      reported or observed in any of the treated patients during the feeding or follow
      up periods. Between weeks 6 and 9 of the study, six of the 14 (43%) evaluable
      subjects who received the study drug achieved a CDAI of 150 or lower. In
      contrast, five of the 15 (33%) evaluable subjects in the placebo group achieved
      remission. Between weeks 9 and 12, the remission rates were 50% and 33% for the
      drug group and placebo group, respectively. Among the drug-treated subjects who
      achieved remission, the effect of the drug was judged as stable in eight of the
      14 subjects as measured by at least two CDAI scores indicating remission in the
      15-wk treatment period. A decreased percentage of peripheral natural killer T
      regulatory cells (a decrease of 28% vs an increase of 16%) and an increased ratio
      of CD4(+)/CD8(+) T lymphocytes (an increase of 11% vs a decrease of 9%) were
      noted in subjects with a significant clinical response. CONCLUSION: Oral
      administration of the autologous colonic extract could be a safe and effective
      for the treatment of patients with moderate to severe Crohn's disease.

PMID- 25987797
TI  - Prevalence of fatty liver disease and the economy in China: A systematic review.
AB  - AIM: To investigate the relationship between the economy and the adult prevalence
      of fatty liver disease (FLD) in mainland China. METHODS: Literature searches on
      the PubMed and Chinese National Knowledge Infrastructure databases were performed
      to identify eligible studies published before July 2014. Records were limited to
      cross-sectional surveys or baseline surveys of longitudinal studies that reported
      the adult prevalence of FLD and recruited subjects from the general population or
      community. The gross domestic product (GDP) per capita was chosen to assess the
      economic status. Multiple linear regression and Loess regression were chosen to
      fit the data and calculate the 95%CIs. Fitting and overfitting of the models were
      considered in choosing the appropriate models. RESULTS: There were 27 population
      based surveys from 26 articles included in this study. The pooled mean prevalence
      of FLD in China was 16.73% (95%CI: 13.92%-19.53%). The prevalence of FLD was
      correlated with the GDP per capita and survey years in the country (adjusted R
      (2) = 0.8736, P GDP per capita = 0.00426, P years = 0.0000394), as well as in
      coastal areas (R (2) = 0.9196, P GDP per capita = 0.00241, P years = 0.00281).
      Furthermore, males [19.28% (95%CI: 15.68%-22.88%)] presented a higher prevalence
      than females [14.1% (95%CI: 11.42%-16.61%), P = 0.0071], especially in coastal
      areas [21.82 (95%CI: 17.94%-25.71%) vs 17.01% (95%CI: 14.30%-19.89%), P =
      0.0157]. Finally, the prevalence was predicted to reach 20.21% in 2020,
      increasing at a rate of 0.594% per year. CONCLUSION: This study reveals a
      correlation between the economy and the prevalence of FLD in mainland China.

PMID- 25987798
TI  - Association of IL-17 polymorphisms with gastric cancer risk in Asian populations.
AB  - AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C
      polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS:
      We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric
      cancer susceptibility systematically. Relevant articles were identified in the
      MEDLINE, Science Citation Index, Cochrane Library, PubMed, EMBASE, CINAHL and
      Current Contents Index databases. We used version 12.0 STATA statistical software
      to evaluate the statistical data. Two reviewers abstracted the data
      independently. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were
      calculated. RESULTS: Seven independent, case-control studies were chosen for the
      meta-analysis, which included 3210 gastric cancer patients and 3889 healthy
      controls. The overall estimation showed a positive association between the IL-17
      rs2275913 G>A polymorphism and the occurrence of gastric cancer for five genetic
      models (all P < 0.05) and similar results were observed for the IL-17 rs763780
      T>C variation with four genetic models (all P < 0.05), but not for the dominant
      model (P > 0.05). Subgroup analysis by country revealed that the rs2275913 G>A
      and rs763780 T>C polymorphisms may be the main risk factor for gastric cancer in
      Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly
      correlated with gastric cancer risk in Asian populations, especially those
      carrying the rs2275913 G>A and rs763780 T>C polymorphisms.

PMID- 25987799
TI  - Systematic review and meta-analysis of prophylactic abdominal drainage after
      pancreatic resection.
AB  - AIM: To investigate whether prophylactic abdominal drainage is necessary after
      pancreatic resection. METHODS: PubMed, Web of Science, and the Cochrane Library
      were systematically searched to obtain relevant articles published before January
      2014. Publications were retrieved if they met the selection criteria. The
      outcomes of interest included: mortality, morbidity, postoperative pancreatic
      fistula (POPF), clinically relevant pancreatic fistula (CR-PF), abdominal
      abscess, reoperation rate, the rate of interventional radiology drainage, and the
      length of hospital stay. Subgroup analyses were also performed for
      pancreaticoduodenectomy (PD) and for distal pancreatectomy. Begg's funnel plot
      and the Egger regression test were employed to assess potential publication bias.
      RESULTS: Nine eligible studies involving a total of 2794 patients were identified
      and included in this meta-analysis. Of the included patients, 1373 received
      prophylactic abdominal drainage. A fixed-effects model meta-analysis showed that
      placement of prophylactic drainage did not have beneficial effects on clinical
      outcomes, including morbidity, POPF, CR-PF, reoperation, interventional radiology
      drainage, and length of hospital stay (Ps > 0.05). In addition, prophylactic
      drainage did not significantly increase the risk of abdominal abscess. Overall
      analysis showed that omitting prophylactic abdominal drainage resulted in higher
      mortality after pancreatectomy (OR = 1.56; 95%CI: 0.93-2.92). Subgroup analysis
      of PD showed similar results to those in the overall analysis. Elimination of
      prophylactic abdominal drainage after PD led to a significant increase in
      mortality (OR = 2.39; 95%CI: 1.22-4.69; P = 0.01). CONCLUSION: Prophylactic
      abdominal drainage after pancreatic resection is still necessary, though more
      evidence from randomized controlled trials assessing prophylactic drainage after
      PD and distal pancreatectomy are needed.

PMID- 25987800
TI  - Left ventricular assist device hemolysis leading to dysphagia.
AB  - A 41-year-old man with a continuous-flow left ventricular assist device presented
      for evaluation of dysphagia and dark urine. He was found to have a significantly
      elevated L-lactate dehydrogenase and an elevated plasma free hemoglobin
      consistent with intravascular hemolysis. After the hemolysis ceased, both the
      black urine and dysphagia resolved spontaneously. Transient esophageal
      dysfunction, as a manifestation of gastrointestinal dysmotility, is known to
      occur in the setting of hemolysis. Paroxysmal nocturnal hemoglobinuria is another
      recognized cause of massive hemolysis with gastrointestinal dysmotility occurring
      in 25%-35% of patients during a paroxysm. Intravascular hemolysis increases
      plasma free hemoglobin, which scavenges nitric oxide (NO), an important second
      messenger for smooth muscle cell relaxation. The decrease in NO can lead to
      esophageal spasm and resultant dysphagia. In our patient the resolution of
      hemolysis resulted in resolution of dysphagia. 

PMID- 25987801
TI  - Esophageal subepithelial lesion diagnosed as malignant gastrointestinal
      neuroectodermal tumor.
AB  - A 21-year-old male visited our hospital with a complaint of aggravating dysphagia
      and odynophagia for a few days. Esophagogastroduodenoscopy showed huge bulging
      mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor
      teeth. Endoscopic ultrasonography showed an about 35 mm sized irregular margined
      in-homogenous hypoechoic lesion with an obscure layer of origin. Endoscopic
      ultrasonography fine needle aspiration revealed spindle cell proliferation
      without immunoreactivity for CD117, SMA, and cytokeratin. The patient underwent
      excision of the subepithelial lesion at the distal esophagus. On pathologic
      examination of the specimen, the tumor was composed of short fascicles of oval to
      spindle cells with eosinophilic and clear cytoplasm and vesicular nuclei. The
      tumor cells were positive for S-100 and SOX10 and negative for CD117, SMA, HMB
      45, melan-A, cytokeratin, and CD99. The split-apart signal was detected in EWSR1
      on FISH, suggesting a malignant gastrointestinal neuroectodermal tumor. At the
      time of writing, the patient is on radiation therapy at the operated site of
      esophagus and doing well, with no recurrence for three months. Malignant
      gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with
      features of clear cell sarcoma, without melanocytic differentiation, and shows a
      poor prognosis. This is the first reported case of malignant gastrointestinal
      neuroectodermal tumor arising as subepithelial lesion in the esophagus.

PMID- 25987803
TI  - Transjugular intrahepatic portosystemic shunt as bridge-to-surgery in refractory
      gastric antral vascular ectasia.
AB  - Gastric antral vascular ectasia (GAVE) may cause gastrointestinal bleeding (GIB).
      The treatment of GAVE relies on endoscopic approaches such as electrocoagulation
      (argon plasma coagulation, laser therapy, heater probe therapy, radiofrequency
      ablation), cryotherapy, and band ligation. In refractory cases, antrectomy may be
      considered. In the event of an associated cirrhosis and portal hypertension, it
      has been suggested that antrectomy could be an option, provided the mortality
      risk isn't considered too great. We report the case of a 67-year-old cirrhotic
      patient who presented with GAVE related GIB, unresponsive to multiple endoscopic
      treatments. The patient had a good liver function (model for end-stage disease
      10). After a multidisciplinary meeting, a transjugular intrahepatic portosystemic
      shunt (TIPS) procedure was performed, in order to treat the cirrhosis associated
      ascites. The outcome was successful. An antrectomy was then performed, with no
      recurrence of GIB and no transfusion need during three months of follow up. In
      this case, the TIPS procedure achieved a complete ascites regression, allowing a
      safer surgical treatment of the GAVE-related GIB. 

PMID- 25987802
TI  - Therapeutic endoscopic retrograde cholangiopancreatography in a patient with
      situs inversus viscerum.
AB  - Situs inversus viscerum (SIV) is a rare congenital condition characterized by
      complete transposition of all viscera. This anatomical pathology makes endoscopic
      retrograde cholangiopancreatography (ERCP) technically difficult. We report a new
      case of a 70-year-old Chinese male with total SIV who had obstructive jaundice.
      Magnetic resonance cholangiopancreatography demonstrated a number of stones in
      the gallbladder and common bile duct (CBD). Therapeutic ERCP was performed to
      relieve biliary obstruction and remove the CBD stones. This procedure started
      with the patient in a supine position and the endoscopist at the left side of the
      table. When the papilla was maintained, the patient was repositioned to a prone
      position and standard endoscopic sphincterotomy and endoscopic papillary balloon
      dilatation procedures were conducted. ERCP was performed successfully and
      relevant complications did not occur in this patient. We also present a review of
      the literature published between 1985 and 2014 in the PubMed and EMBASE
      databases. There were eight published cases during this period, with one each
      from America, Finland, India, Italy, South Korea and Pakistan, and two from
      Spain. Our case is the first reported in China. 

PMID- 25987805
TI  - The nature and meaning of insulin pump use in emerging adults with type 1
      diabetes.
AB  - Objective. The purpose of this study is to investigate the meaning of living with
      an insulin pump for the management of type 1 diabetes during the period of
      emerging adulthood. Through a phenomenological narrative, this study contributes
      to the reflective understanding of the everyday life experiences of this
      population. Methods. A hermeneutic phenomenological design was used for this
      study of nine emerging adults (aged 19-24 years). Data were generated through
      face-to-face interviews and analyzed using the phenomenological approach of Max
      van Manen. Results. Four themes represent the essence of the day-to-day
      experiences of these emerging adults: seeking control, becoming responsible,
      staying connected, and accepting me. Conclusions. An in-depth understanding of
      the meaning of daily experiences with insulin pump technology has the potential
      to promote a developmentally appropriate approach to this age-group. The human
      understanding gained through this study is essential to the development of
      evidence-based practice guidelines and resources for this vulnerable population. 

PMID- 25987804
TI  - Are children on jejunal feeds at risk of iron deficiency?
AB  - Children on exclusive jejunal feeding may be at risk of iron deficiency due to
      the feeds bypassing the duodenum, which is the primary site for iron absorption.
      We describe the biochemical and hematological features of six children on
      exclusive jejunal feeding who did not receive iron supplementation. At a mean
      (standard deviation) period of 11 (6.5) mo after commencing jejunal feeds, there
      was a significant reduction in both serum iron (18.5 g/L vs 9.8 g/L, P = 0.01)
      and transferrin saturation levels (23.1% vs 13.7%, P = 0.02), suggesting iron
      deficiency. However, there was no significant change in ferritin, hemoglobin and
      mean corpuscular volume levels post-commencement of jejunal feeds. This may be
      the result of small bowel adaptation in response to early iron deficiency. Larger
      and longer term prospective studies are required to investigate if children on
      jejunal feeds are at risk of developing iron deficiency. 

PMID- 25987806
TI  - Going mobile with diabetes support: a randomized study of a text message-based
      personalized behavioral intervention for type 2 diabetes self-care.
AB  - Objective. Patients with type 2 diabetes often fail to achieve self-management
      goals. This study tested the impact on glycemic control of a two-way text
      messaging program that provided behavioral coaching, education, and testing
      reminders to enrolled individuals with type 2 diabetes in the context of a clinic
      based quality improvement initiative. The secondary aim examined patient
      interaction and satisfaction with the program. Methods. Ninety-three adult
      patients with poorly controlled type 2 diabetes (A1C >8%) were recruited from 18
      primary care clinics in three counties for a 6-month study. Patients were
      randomized by a computer to one of two arms. Patients in both groups continued
      with their usual care; patients assigned to the intervention arm also received
      from one to seven diabetes-related text messages per day depending on the choices
      they made at enrollment. At 90 and 180 days, A1C data were obtained from the
      electronic health record and analyzed to determine changes from baseline for both
      groups. An exit survey was used to assess satisfaction. Enrollment behavior and
      interaction data were pulled from a Web-based administrative portal maintained by
      the technology vendor. Results. Patients used the program in a variety of ways.
      Twenty-nine percent of program users demonstrated frequent engagement (texting
      responses at least three times per week) for a period of >=90 days. Survey
      results indicate very high satisfaction with the program. Both groups' average
      A1C decreased from baseline, possibly reflecting a broader quality improvement
      effort underway in participating clinics. At 90 and 180 days, there was no
      statistically significant difference between the intervention and control groups
      in terms of change in A1C (P >0.05). Conclusions. This study demonstrated a
      practical approach to implementing and monitoring a mobile health intervention
      for self-management support across a wide range of independent clinic practices. 

PMID- 25987808
TI  - Targeted recruitment of adults with type 2 diabetes for a physical activity
      intervention.
AB  - Recruiting sufficient numbers of participants for physical activity trials for
      individuals with diabetes can be difficult because there are often many
      behavioral demands for participants, and inclusion and exclusion criteria can be
      extensive. This study examined the recruitment strategies used for a randomized,
      controlled trial designed to investigate the efficacy of an automated telephone
      intervention to promote physical activity in adults with type 2 diabetes in an
      urban Veterans Administration health care system. Traditional recruitment
      approaches of posting flyers and obtaining referrals from clinicians did not
      yield sufficient numbers of interested patients. Using the electronic medical
      record system to identify patients with uncontrolled diabetes allowed staff to
      send targeted mailings to participants, and 77% of participants were recruited
      using this method. The targeted mailing approach elicited a positive response
      rate of 12% (328 of 2,764 potential participants identified) and appeared to
      produce a more representative and appropriate sample than other recruitment
      methods used. Lessons learned in this study may be helpful to researchers in
      future trials who attempt to recruit participants with diabetes for physical
      activity protocols. 

PMID- 25987807
TI  - Using photography as a method to explore adolescent challenges and resilience in
      type 1 diabetes.
AB  - Patient-centered approaches to disease management are consistently recognized as
      valuable tools for improving health outcomes, yet studies are rarely designed to
      elicit adolescent perspectives. This study sought to better understand the
      perspectives of youths with type 1 diabetes according to key demographic
      variables. We conducted an exploratory study through which 40 youths were
      provided with disposable cameras and prompted to take five photographs each that
      captured what diabetes meant to them and to provide narratives to accompany their
      photo choices. Demographic variables examined included sex, age, disease
      duration, socioeconomic status (SES), race, and glycemic control (A1C). Content
      analysis was used for photos and open-ended responses to assign photo index
      scores, which were then analyzed by demographic variables using Mann-Whitney U
      tests for statistical significance. Analysis of photos/narratives (n = 202)
      revealed five main types of representations depicted by at least 50% of the young
      people. "Challenge" photos included diabetes supplies as tethering, food as a
      source of frustration, and the body as a territory for disease encroachment.
      "Resilience" photos included coping mechanisms and symbols of resistance.
      Overall, these representations were consistent across demographic categories with
      two exceptions. Males took more food depictions than females (P <0.005) and had
      fewer coping depictions (P <0.05). Youths from more affluent households were more
      likely to take photos of resistance (P <0.05). The use of photo index scores
      expands previous studies using photography by comparing demographic variation
      within a sample. Our findings provide insight into coping strategies and indicate
      that SES may provide an advantage for affluent youths in meeting diabetes
      specific challenges. 

PMID- 25987809
TI  - Translating an evidence-based diabetes education approach into rural african
      american communities: the "wisdom, power, control" program.
AB  - Purpose. The aim of this exploratory study was to assess the efficacy of the
      "Wisdom, Power, Control" diabetes self-management education (DSME) program with
      regard to diabetes knowledge, self-efficacy, self-care, distress level, and A1C
      in an African-American population. Methods. A prospective, quasi-experimental,
      repeated-measure design was employed to measure these outcomes. Study
      participants were assessed at baseline, 6 weeks post-intervention, and at a 3
      month A1C follow-up. Results. A total of 103 participants were recruited from the
      intervention counties, and 14 were identified from the control counties. At the
      post-test, participants in the intervention group reported a significantly higher
      level of diabetes knowledge (Delta = 9.2%, P <0.0001), higher self-efficacy
      (Delta = 0.60, P <0.0001), more self-care behaviors (Delta = 0.48, P <0.0001),
      lower distress level (Delta = -0.15, P = 0.05), and higher health status (Delta =
      0.49, P = <0.0001). About 56% of the intervention group completed all six
      classes, and 25% attended five classes. Conclusions. Findings from this study
      demonstrate the initial success of translating a culturally adapted DSME program
      into rural African-American communities. The study highlights important lessons
      learned in the process of implementing this type of program in a real-world
      setting with a minority population. 

PMID- 25987810
TI  - The role of polycystic ovary syndrome in reproductive and metabolic health:
      overview and approaches for treatment.

PMID- 25987811
TI  - Case Study: Use of GLP-1 Receptor Agonist in a Patient on Intensive Insulin
      Therapy.

PMID- 25987812
TI  - Assessment of group-based diabetes education using the "continuing your journey
      with diabetes" conversation map in the veteran population.

PMID- 25987813
TI  - Health care transformation initiatives in type 2 diabetes care: a qualitative
      study in the cincinnati beacon community.

PMID- 25987814
TI  - The times they are a-changin'.

PMID- 25987815
TI  - Six impossible things before breakfast: examining diabetes self-care.

PMID- 25987817
TI  - Chipping away at antibiotic resistance, hideous hospital gowns, and other health
      care woes.
AB  - Sessions on antibiotics at a pharmacists' convention help put a 14-year-old case
      of strep throat in perspective, showing what has changed, what hasn't, and what
      should. But there's hope on the horizon (for antibiotics and for those gowns,
      too). 

PMID- 25987816
TI  - P&T committees face new medicare rules: proof needed of "independent" members'
      independence.
AB  - Seeking proof of P&T committee members' independence. 

PMID- 25987818
TI  - Inappropriate Use of Pharmacy Bulk Packages of IV Contrast Media Increases the
      Risk of Infections.
AB  - Bulk packages of IV contrast media used inappropriately. 

PMID- 25987820
TI  - Pharmaceutical approval update.
AB  - Filgrastim-sndz (Zarxio) to help prevent infections related to chemotherapy,
      dinutuximab (Unituxin) for high-risk pediatric neuroblastoma, and panobinostat
      (Farydak) for multiple myeloma. 

PMID- 25987822
TI  - Precision medicine initiative aims for a new generation of diagnostics and
      treatments: but is the promise of genetic targeting overinflated?
AB  - Washington politicians appear to agree on the need for a vigorous effort to
      develop genetic tests and targeted, genomic medicines that reach small
      populations within specific disease groups. Still, the quest for "precision
      medicine" has some skeptics. 

PMID- 25987821
TI  - Ferric citrate (auryxia) for the treatment of hyperphosphatemia.
AB  - Ferric citrate (Auryxia) for the treatment of hyperphosphatemia. 

PMID- 25987823
TI  - The antibiotic resistance crisis: part 2: management strategies and new agents.
AB  - Controlling antibiotic-resistant bacteria calls for widespread adoption of
      antibiotic stewardship programs; better diagnosis, tracking and prescribing
      practices; optimized therapeutic regimens; prevention of infection transmission
      and new drugs. 

PMID- 25987824
TI  - Customized order-entry sets can prevent antiretroviral prescribing errors: a
      novel opportunity for antimicrobial stewardship.
AB  - BACKGROUND: Patients with human immunodeficiency virus (HIV) infection on
      antiretroviral (ARV) therapy are at increased risk for medication errors during
      transitions of care between the outpatient and inpatient settings. This can lead
      to treatment failure or toxicity. Previous studies have emphasized the prevalence
      of medication errors in such patients, but few have reported initiatives to
      prevent errors from occurring. METHODS: The study was conducted in a 1,400-bed
      health care center with a state-designated Acquired Immunodeficiency Syndrome
      (AIDS) Center in the Bronx, New York. The antimicrobial stewardship team and HIV
      specialists developed customized order-entry sets (COES) to guide ARV prescribing
      and retrospectively reviewed their effect on error rates of initial ARV orders
      for inpatients before reconciliation. Patient records were reviewed in six-month
      periods before and after intervention. The student's t-test or Mann-Whitney U
      test was used to compare continuous variables; chi-square or Fisher's exact test
      was used for categorical variables. RESULTS: A total of 723 and 661 admissions
      were included in the pre-intervention and post-intervention periods,
      respectively. Overall, error rates decreased by 35% (38.0% to 24.8%, P < 0.01)
      with COES. Wrong doses and drug interactions decreased by more than 40% (P <
      0.005). Error reductions were observed in protease inhibitor (PI)-based (43.6%
      versus 28.7%, P < 0.01) and non-PI-based (38.0% versus 24.4%, P = 0.02) regimens
      with COES. A shift in predominant drug-class errors was observed as there was a
      trend toward increased usage of non-PI regimens post-intervention. Admission in
      the pre-intervention period (adjusted odds ratio [AOR], 1.79; 95% confidence
      interval [CI], 1.39-2.31) and use of PI-based regimens (AOR, 2.03; 95% CI, 1.53
      2.70) remained significantly associated with ARV prescribing errors after
      controlling for confounding factors. CONCLUSION: Detailed COES improved ARV
      prescribing habits, reduced the potential for prescribing incorrect regimens, and
      can prove useful and cost-effective where HIV-specific medication reconciliation
      is unavailable.

PMID- 25987825
TI  - American college of cardiology: 64th annual scientific session and expo.
AB  - Topics included a new agent to lower cholesterol and the use of cangrelor,
      bivalirudin, unfractionated heparin, ticagrelor, and Bendavia for acute coronary
      syndromes. 

PMID- 25987826
TI  - In the Crowded HIV Market, There's Room for Innovation.
AB  - As researchers seek more-effective, safer medications to treat human
      immunodeficiency virus, the focus has shifted to fixed-dose, single-tablet
      combinations. 

PMID- 25987827
TI  - BIR Pipeline for Preparation of Phylogenomic Data.
AB  - SUMMARY: We present a pipeline named BIR (Blast, Identify and Realign) developed
      for phylogenomic analyses. BIR is intended for the identification of gene
      sequences applicable for phylogenomic inference. The pipeline allows users to
      apply their own manually curated sequence alignments (seed) in search for
      homologous genes in sequence databases and available genomes. BIR automatically
      adds the identified sequences from these databases to the seed alignments and
      reconstruct a phylogenetic tree from each. The BIR pipeline is an efficient tool
      for the identification of orthologous gene copies because it expands user-defined
      sequence alignments and conducts massive parallel phylogenetic reconstruction.
      The application is also particularly useful for large-scale sequencing projects
      that require management of a large number of single-gene alignments for gene
      comparison, functional annotation, and evolutionary analyses. AVAILABILITY: The
      BIR user manual is available at http://www.bioportal.no/ and can be accessed
      through Lifeportal at https://lifeportal.uio.no. Access is free but requires a
      user account registration using the link "Register for BIR access" from the
      Lifeportal homepage.

PMID- 25987828
TI  - Roles of solvent accessibility and gene expression in modeling protein sequence
      evolution.
AB  - Models of protein evolution tend to ignore functional constraints, although
      structural constraints are sometimes incorporated. Here we propose a
      probabilistic framework for codon substitution that evaluates joint effects of
      relative solvent accessibility (RSA), a structural constraint; and gene
      expression, a functional constraint. First, we explore the relationship between
      RSA and codon usage at the genomic scale as well as at the individual gene scale.
      Motivated by these results, we construct our framework by determining how
      probable is an amino acid, given RSA and gene expression, and then evaluating the
      relative probability of observing a codon compared to other synonymous codons. We
      come to the biologically plausible conclusion that both RSA and gene expression
      are related to amino acid frequencies, but, among synonymous codons, the relative
      probability of a particular codon is more closely related to gene expression than
      RSA. To illustrate the potential applications of our framework, we propose a new
      codon substitution model. Using this model, we obtain estimates of 2N s, the
      product of effective population size N, and relative fitness difference of allele
      s. For a training data set consisting of human proteins with known structures and
      expression data, 2N s is estimated separately for synonymous and nonsynonymous
      substitutions in each protein. We then contrast the patterns of synonymous and
      nonsynonymous 2N s estimates across proteins while also taking gene expression
      levels of the proteins into account. We conclude that our 2N s estimates are too
      concentrated around 0, and we discuss potential explanations for this lack of
      variability. 

PMID- 25987829
TI  - Genomic Analysis of the BMP Family in Glioblastomas.
AB  - Glioblastoma multiforme (GBM) is a grade IV glioma with a median survival of 15
      months. Recently, bone morphogenetic protein (BMP) signaling has been shown to
      promote survival in xenograft murine models. To gain a better understanding of
      the role of BMP signaling in human GBMs, we examined the genomic alterations of
      90 genes associated with BMP signaling in GBM patient samples. We completed this
      analysis using publically available datasets compiled through Te Cancer Genome
      Atlas and the Glioma Molecular Diagnostic Initiative. Here we show how mRNA
      expression is altered in GBM samples and how that is associated with patient
      survival, highlighting both known and novel associations between BMP signaling
      and GBM biology. 

PMID- 25987830
TI  - Applications of second-harmonic generation imaging microscopy in ovarian and
      breast cancer.
AB  - In this perspective, we discuss how the nonlinear optical technique of second
      harmonic generation (SHG) microscopy has been used to greatly enhance our
      understanding of the tumor microenvironment (TME) of breast and ovarian cancer.
      Striking changes in collagen architecture are associated with these epithelial
      cancers, and SHG can image these changes with great sensitivity and specificity
      with submicrometer resolution. This information has not historically been
      exploited by pathologists but has the potential to enhance diagnostic and
      prognostic capabilities. We summarize the utility of image processing tools that
      analyze fiber morphology in SHG images of breast and ovarian cancer in human
      tissues and animal models. We also describe methods that exploit the SHG physical
      underpinnings that are effective in delineating normal and malignant tissues.
      First we describe the use of polarization-resolved SHG that yields metrics
      related to macromolecular and supramolecular structures. The coherence and
      corresponding phase-matching process of SHG results in emission directionality
      (forward to backward), which is related to sub-resolution fibrillar assembly.
      These analyses are more general and more broadly applicable than purely
      morphology-based analyses; however, they are more computationally intensive.
      Intravital imaging techniques are also emerging that incorporate all of these
      quantitative analyses. Now, all these techniques can be coupled with rapidly
      advancing miniaturization of imaging systems to afford their use in clinical
      situations including enhancing pathology analysis and also in assisting in real
      time surgical determination of tumor margins. 

PMID- 25987832
TI  - Virtual glaucoma clinics: patient acceptance and quality of patient education
      compared to standard clinics.
AB  - PURPOSE: Virtual glaucoma clinics allow rapid, reliable patient assessment but
      the service should be acceptable to patients and concordance with treatment needs
      to be maintained with adequate patient education. This study compares experiences
      and understanding of patients reviewed via the virtual clinic versus the standard
      clinic by way of an extended patient satisfaction questionnaire (PSQ). PATIENTS
      AND METHODS: One hundred PSQs were given to consecutive patients attending
      glaucoma clinics in October 2013. All 135 patients reviewed via the virtual
      clinic from April 2013 until August 2013 were sent postal PSQs in September 2013.
      Data were obtained for demographics, understanding of glaucoma, their condition,
      satisfaction with their experience, and quality of information. Responses were
      analyzed in conjunction with the clinical records. RESULTS: Eighty-five percent
      of clinic patients and 63% of virtual clinic patients responded to the PSQ. The
      mean satisfaction score was over 4.3/5 in all areas surveyed. Virtual clinic
      patients' understanding of their condition was very good, with 95% correctly
      identifying their diagnosis as glaucoma, 83% as ocular hypertension and 78% as
      suspects. There was no evidence to support inferior knowledge or self-perceived
      understanding compared to standard clinic patients. Follow-up patients knew more
      about glaucoma than new patients. Over 95% of patients found our information
      leaflet useful. Forty percent of patients sought additional information but less
      than 20% used the internet for this. CONCLUSION: A substantial proportion of
      glaucoma pathway patients may be seen by non-medical staff supervised by glaucoma
      specialists via virtual clinics. Patients are accepting of this format, reporting
      high levels of satisfaction and non-inferior knowledge to those seen in standard
      clinics.

PMID- 25987831
TI  - Current and emerging treatment options for myopic choroidal neovascularization.
AB  - Choroidal neovascularization (CNV) is the main cause of visual impairment in
      highly myopic patients younger than 50 years of age. There are different
      treatments for myopic CNV (mCNV), with 5- to 10-year outcomes currently.
      Chorioretinal atrophy is still the most important determinant factor for visual
      outcome. The purpose of this study is to provide an overview of the current
      treatments for mCNV, including laser, surgical management, verteporfin
      photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy.
      Emerging treatment options are also discussed. 

PMID- 25987833
TI  - Comparative fasting bioavailability of two clopidogrel formulations in healthy
      Mediterranean volunteers: an in vitro-in vivo correlation.
AB  - OBJECTIVE: The aim of this study was to evaluate the bioequivalence of two drug
      products, generic clopidogrel bisulfate 75 mg film-coated tablets versus the
      reference Plavix((r)) clopidogrel bisulfate 75 mg film-coated tablets. METHODS:
      Bioequivalence of tablets was tested by comparisons against the reference brand
      product in accordance with the requirements of the Declaration of Helsinki, the
      current Good Clinical Practice Guidelines, and the International Conference on
      Harmonization. RESULTS: The relationship between concentration and peak area
      ratio was found to be linear within the range 24.500-1,836.600 pg/mL for
      clopidogrel. The correlation coefficient (r) was always greater than 0.99 during
      the course of the validation. Statistical comparison of the main pharmacokinetic
      parameters showed no significant difference between test and reference. The point
      estimates (ratios of geometric mean) were 104.122%, 104.184%, and 109.091% for
      areas under the plasma concentration-time curve (AUC) AUC0-last, AUC0-infinity,
      and peak plasma concentration C max, respectively. These pharmacokinetic
      parameter values of clopidogrel and its main metabolite lie within the
      bioequivalence limit (80%-125%) specified by the US Food and Drug Administration
      and the European Medicines Agency. CONCLUSION: The tested drug product was
      bioequivalent to the reference drug under fasting conditions and had the same
      safety profile, which is important to achieve equivalent therapeutic effect with
      the reference.

PMID- 25987834
TI  - Changing the face of hepatitis C management - the design and development of
      sofosbuvir.
AB  - The availability of direct-acting antiviral (DAA) therapy has launched a new era
      in the management of chronic hepatitis C. Sofosbuvir, a uridine nucleotide analog
      that inhibits the hepatitis C RNA-dependent RNA polymerase, is the backbone of
      chronic hepatitis C therapy. Acting at the catalytic site of the polymerase,
      sofosbuvir is highly potent in suppressing viral replication and has a high
      genetic barrier to resistance. Sofosbuvir is effective across all hepatitis C
      genotypes, and is a mainstay of interferon-free combination therapy. In Phase II
      and III studies, genotype 1 patients who took sofosbuvir in combination with
      another DAA such as the NS3-4A protease inhibitor, simeprevir, or the NS5A
      replication complex inhibitors, ledipasvir or daclatasvir, achieved a sustained
      virologic response rate of over 90%. Harvoni((r)), a combination tablet of
      sofosbuvir and ledipasvir, dosed once daily is recommended for 24 weeks for
      treatment-experienced genotype 1 patients with cirrhosis, but 12 weeks of therapy
      is sufficient for all other populations. While genotype 2 (12 weeks or 16 weeks)
      and treatment-naive genotype 3 patients (24 weeks) have excellent response rates
      with sofosbuvir and ribavirin, treatment-experienced cirrhotic genotype 3
      patients may need the addition of another DAA such as daclatasvir. Sofosbuvir is
      efficacious in special populations such as HIV-hepatitis C virus-coinfected
      patients and liver transplant recipients and has already made a profound impact
      in these groups. Since it is renally eliminated, patients with advanced kidney
      disease or on dialysis must await dosing recommendations. Sofosbuvir-based
      regimens appear to be well tolerated with headache and fatigue being the most
      common side effects. The opportunity to cure patients with hepatitis C with
      sofosbuvir combination therapy is likely to change the future for our patients,
      particularly if the emphasis shifts to identifying those patients unaware that
      they are infected and providing affordable access to treatment. 

PMID- 25987835
TI  - Apolipoprotein M regulates the orphan nuclear receptor LRH-1 gene expression
      through binding to its promoter region in HepG2 cells.
AB  - Apolipoprotein M (ApoM) is predominantly located in the high-density lipoprotein
      in human plasma. It has been demonstrated that ApoM expression could be regulated
      by several crucial nuclear receptors that are involved in the bile acid
      metabolism. In the present study, by combining gene-silencing experiments,
      overexpression studies, and chromatin immunoprecipitation assays, we showed that
      ApoM positively regulated liver receptor homolog-1 (LRH-1) gene expression via
      direct binding to an LRH-1 promoter region (nucleotides -406/ -197). In addition,
      we investigated the effects of farnesoid X receptor agonist GW4064 on hepatic
      ApoM expression in vitro. In HepG2 cell cultures, both mRNA and protein levels of
      ApoM and LRH-1 were decreased in a time-dependent manner in the presence of 1 MUM
      GW4064, and the inhibition effect was gradually attenuated after 24 hours. In
      conclusion, our findings present supportive evidence that ApoM is a regulator of
      human LRH-1 transcription, and further reveal the importance of ApoM as a
      critical regulator of bile acids metabolism. 

PMID- 25987836
TI  - Structure-activity exploration of a small-molecule Lipid II inhibitor.
AB  - We have recently identified low-molecular weight compounds that act as inhibitors
      of Lipid II, an essential precursor of bacterial cell wall biosynthesis. Lipid II
      comprises specialized lipid (bactoprenol) linked to a hydrophilic head group
      consisting of a peptidoglycan subunit (N-acetyl glucosamine [GlcNAc]-N-acetyl
      muramic acid [MurNAc] disaccharide coupled to a short pentapeptide moiety) via a
      pyrophosphate. One of our lead compounds, a diphenyl-trimethyl indolene pyrylium,
      termed BAS00127538, interacts with the MurNAc moiety and the isoprenyl tail of
      Lipid II. Here, we report on the structure-activity relationship of BAS00127538
      derivatives obtained by in silico analyses and de novo chemical synthesis. Our
      results indicate that Lipid II binding and bacterial killing are related to three
      features: the diphenyl moiety, the indolene moiety, and the positive charge of
      the pyrylium. Replacement of the pyrylium moiety with an N-methyl pyridinium,
      which may have importance in stability of the molecule, did not alter Lipid II
      binding or antibacterial potency. 

PMID- 25987837
TI  - Development of acquired factor V inhibitor after treatment with ceftazidime: a
      case report and review of the literature.
AB  - We report the case of a 59-year-old Chinese man who showed an asymptomatic
      coagulation factor V deficiency pattern after second intravenous treatment with
      ceftazidime. Normal pooled plasma failed to correct the abnormalities in a mixing
      test, and the presence of factor V inhibitor was confirmed by the Bethesda
      method. The coagulopathy was not corrected by transfusion of fresh frozen plasma
      and prothrombin complex concentrate, but rather by treatment with prednisone and
      withdrawal of dubious drugs. The findings reported here should prompt clinicians
      to watch for drug-induced coagulation factor deficiency. 

PMID- 25987838
TI  - Gold nanoparticle-based beacon to detect STAT5b mRNA expression in living cells:
      a case optimized by bioinformatics screen.
AB  - Messenger RNA (mRNA), a single-strand ribonucleic acid with functional gene
      information is usually abnormally expressed in cancer cells and has become a
      promising biomarker for the study of tumor progress. Hairpin DNA-coated gold
      nanoparticle (hDAuNP) beacon containing a bare gold nanoparticle (AuNP) as
      fluorescence quencher and thiol-terminated fluorescently labeled stem-loop-stem
      oligonucleotide sequences attached by Au-S bond is currently a new nanoscale
      biodiagnostic platform capable of mRNA detection, in which the design of the loop
      region sequence is crucial for hybridizing with the target mRNA. Hence, in this
      study, to improve the sensitivity and selectivity of hDAuNP beacon
      simultaneously, the loop region of hairpin DNA was screened by bioinformatics
      strategy. Here, signal transducer and activator of transcription 5b (STAT5b) mRNA
      was selected and used as a practical example. The results from the combined
      characterizations using optical techniques, flow cytometry assay, and cell
      microscopic imaging showed that after optimization, the as-prepared hDAuNP beacon
      had higher selectivity and sensitivity for the detection of STAT5b mRNA in living
      cells, as compared with our previous beacon. Thus, the bioinformatics method may
      be a promising new strategy for assisting in the designing of the hDAuNP beacon,
      extending its application in the detection of mRNA expression and the resultant
      mRNA-based biological processes and disease pathogenesis. 

PMID- 25987839
TI  - Low-density lipoprotein cholesterol of less than 70 mg/dL is associated with
      fewer cardiovascular events in acute coronary syndrome patients: a real-life
      cohort in Thailand.
AB  - BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) is associated
      with an increased risk of cardiovascular disease or mortality; however, the LDL-C
      goal for therapy in acute coronary syndrome (ACS) patients is controversial and
      varies among guidelines. This study aimed to assess the effect of reaching an LDL
      C goal of <70 mg/dL (<1.8 mmol/L) on first composite cardiovascular outcomes in
      routine clinical practice in Thailand. METHODS: A retrospective cohort study was
      conducted using medical charts and the electronic hospital database of patients
      diagnosed with ACS and treated with statins at a tertiary care hospital in
      Thailand between 2009 and 2012. After admission, patients were followed from the
      date of LDL-C goal assessment until the first event of composite cardiovascular
      outcomes (nonfatal ACS, nonfatal stroke, or all-cause death). Cox proportional
      hazard models adjusted for potential confounders were used. RESULTS: Of 405
      patients, mean age was 65 years (60% males). Twenty-seven percent of the patients
      attained an LDL-C goal of <70 mg/dL, 38% had LDL-C between 70 and 99 mg/dL, and
      35% had LDL-C >=100 mg/dL. Forty-six patients experienced a composite
      cardiovascular outcome. Compared with patients with an LDL-C >=100 mg/dL,
      patients achieving an LDL-C of <70 mg/dL were associated with a reduced composite
      cardiovascular outcome (adjusted hazard ratio [HR]=0.42; 95% confidence interval
      [CI]=0.18-0.95; P-value=0.037), but patients with an LDL-C between 70 and 99
      mg/dL had a lower composite cardiovascular outcome, which was not statistically
      significant (adjusted HR=0.73; 95% CI=0.37-1.42; P-value=0.354). CONCLUSION: ACS
      patients who received statins and achieved an LDL-C of <70 mg/dL had
      significantly fewer composite cardiovascular outcomes, confirming "the lower the
      better" and the benefit of treating to LDL-C target in ACS patient management.

PMID- 25987840
TI  - Reduced Efficacy of Commercial Acaricides Against Populations of Resistant Cattle
      Tick Rhipicephalus microplus from Two Municipalities of Antioquia, Colombia.
AB  - Two distant Antioquian cattle farms where systemic and topical acaricides had
      previously failed to control infestations by Rhipicephalus (Boophilus) microplus
      were studied. An initial in vivo study was conducted using single subcutaneous
      injections with a long-acting formulation of ivermectin (630 MUg/kg). Injections
      were made at 3-month intervals on animals at each farm to evaluate the
      therapeutic and persistent efficacy of ivermectin against R. microplus. Body tick
      counts and reproductive parameters of semi- or fully engorged females (>=5 mm)
      were assessed at 10-day intervals, and since no negative control group could be
      included, values were compared against those for day 0. Although there was an
      overall reduction of 50%-75% in tick numbers that persisted for 30-40 days, it
      was not significantly different at one of the farms and not enough to afford
      protection from severe infestations. The engorgement weight and egg mass weight
      of ticks from treated animals were significantly lower throughout the 50-day
      posttreatment period. Egg hatch was not significantly reduced posttreatment and
      remained at levels of 80%-90%. A random selection of 9 out of 28 commercial
      formulations of ivermectin sold in Colombia were analyzed by High Performance
      Liquid Chromatography (HPLC). All were within the expected labeled concentration
      (+/-15% deviation) of 1% and 3.15% ivermectin except for one. A popular
      unregistered injectable widely used in both farms and labeled as "natural
      pyrethrin", was found to contain 10.5% ivermectin. An adult immersion test was
      conducted to evaluate the efficacy of topical acaricides to recommended
      concentrations of five commercial products and/or their combinations. Efficacy
      was determined by comparing the reproductive index of each treated group to that
      of the control group. Cypermethrin (150 ppm) was completely ineffective at both
      farms. Amitraz (208 ppm) exhibited low and intermediate efficacies of 14% and
      56%. The combination of amitraz (100 ppm) and cypermethrin (150 ppm) was less
      efficacious than the amitraz alone. A generic product based on amitraz +
      citronella (208 ppm + 10 ppm, respectively) was shown to be less efficacious than
      the name-brand amitraz product. Products containing the organophosphate
      chlorpyrifos or trichlorfon exhibited intermediate efficacies of approximately
      60% at the Tarso farm. We conclude that at these two locations, there is a high
      degree of resistance to many of the acaricides available in Colombia and confirm
      suspicions that ivermectin is no longer able to eliminate tick infestations. 

PMID- 25987841
TI  - Observed loss and ineffectiveness of mosquito larvicides applied to catch basins
      in the northern suburbs of chicago IL, 2014.
AB  - In the northeastern part of the greater Chicago metropolitan area, the North
      Shore Mosquito Abatement District (NSMAD) treats approximately 50,000 catch
      basins each season with larvicide tablets as part of its effort to reduce local
      populations of the West Nile virus (WNV) vector Culex pipiens. During the 2014
      season, an NSMAD technician monitored a subset of 60-195 basins weekly for 18
      weeks among the communities of the District for the presence of mosquitoes.
      Monitoring found no clear evidence in the reduction of mosquitoes with the use of
      larvicides, and visual inspections of 211 larvicide-treated basins found that the
      majority (162, 76.8%) were missing tablets 1-17 weeks after applications. This
      loss of treatment may be due to the rapid dissolution or flushing of larvicides
      and would help explain why the larvicide appeared to be ineffective. 

PMID- 25987842
TI  - Aerosol optical depth as a measure of particulate exposure using imputed censored
      data, and relationship with childhood asthma hospital admissions for 2004 in
      athens, Greece.
AB  - An understanding of human health implications from atmosphere exposure is a
      priority in both the geographic and the public health domains. The unique
      properties of geographic tools for remote sensing of the atmosphere offer a
      distinct ability to characterize and model aerosols in the urban atmosphere for
      evaluation of impacts on health. Asthma, as a manifestation of upper respiratory
      disease prevalence, is a good example of the potential interface of geographic
      and public health interests. The current study focused on Athens, Greece during
      the year of 2004 and (1) demonstrates a systemized process for aligning data
      obtained from satellite aerosol optical depth (AOD) with geographic location and
      time, (2) evaluates the ability to apply imputation methods to censored data, and
      (3) explores whether AOD data can be used satisfactorily to investigate the
      association between AOD and health impacts using an example of hospital admission
      for childhood asthma. This work demonstrates the ability to apply remote sensing
      data in the evaluation of health outcomes, that the alignment process for remote
      sensing data is readily feasible, and that missing data can be imputed with a
      sufficient degree of reliability to develop complete datasets. Individual
      variables demonstrated small but significant effect levels on hospital admission
      of children for AOD, nitrogen oxides (NOx), relative humidity (rH), temperature,
      smoke, and inversely for ozone. However, when applying a multivari-able model, an
      association with asthma hospital admissions and air quality could not be
      demonstrated. This work is promising and will be expanded to include additional
      years. 

PMID- 25987843
TI  - Carbon Disulfide (CS2) Mechanisms in Formation of Atmospheric Carbon Dioxide
      (CO2) Formation from Unconventional Shale Gas Extraction and Processing
      Operations and Global Climate Change.
AB  - Carbon disulfide (CS2) has been historically associated with the production of
      rayon, cellophane, and carbon tetrachloride. This study identifies multiple
      mechanisms by which CS2 contributes to the formation of CO2 in the atmosphere.
      CS2 and other associated sulfide compounds were found by this study to be present
      in emissions from unconventional shale gas extraction and processing (E&P)
      operations. The breakdown products of CS2; carbonyl sulfide (COS), carbon
      monoxide (CO), and sulfur dioxide (SO2) are indirect greenhouse gases (GHGs) that
      contribute to CO2 levels in the atmosphere. The heat-trapping nature of CO2 has
      been found to increase the surface temperature, resulting in regional and global
      climate change. The purpose of this study is to identify five mechanisms by which
      CS2 and the breakdown products of CS2 contribute to atmospheric concentrations of
      CO2. The five mechanisms of CO2 formation are as follows: Chemical Interaction of
      CS2 and hydrogen sulfide (H2S) present in natural gas at high temperatures,
      resulting in CO2 formation;Combustion of CS2 in the presence of oxygen producing
      SO2 and CO2;Photolysis of CS2 leading to the formation of COS, CO, and SO2, which
      are indirect contributors to CO2 formation;One-step hydrolysis of CS2, producing
      reactive intermediates and ultimately forming H2S and CO2;Two-step hydrolysis of
      CS2 forming the reactive COS intermediate that reacts with an additional water
      molecule, ultimately forming H2S and CO2. CS2 and COS additionally are implicated
      in the formation of SO2 in the stratosphere and/or troposphere. SO2 is an
      indirect contributor to CO2 formation and is implicated in global climate change.

PMID- 25987844
TI  - Sustainable watersheds: integrating ecosystem services and public health.
AB  - Sustainable management of aquatic ecosystems is a worldwide priority; the
      integrity of these systems depends, in turn, on the integrity of the watersheds
      (catchments) in which they are embedded. In this article, we present the
      concepts, background, and scientific foundations for assessing, both nationally
      and at finer scales, the relationships between ecosystem services, human health,
      and socioeconomic values in the context of water quality, water quantity,
      landscapes, the condition of watersheds, and the connectivity of waters, from
      headwaters to estuaries and the coastal ocean. These assessments will be a
      foundation for what we have termed "watershed epidemiology," through which the
      connections between ecosystems and human health can be explored over broad
      spatial and temporal scales. Understanding and communicating these relationships
      should lead to greater awareness of the roles watersheds play in human well
      being, and hence to better management and stewardship of water resources. The
      U.S. Environmental Protection Agency is developing the research, models, and
      planning tools to support operational national assessments of watershed
      sustainability, building upon ongoing assessments of aquatic resources in
      streams, rivers, lakes, wetlands and estuaries. 

PMID- 25987845
TI  - Efficiency of health care in state correctional institutions.
AB  - Little is known about the efficiency of health care in correction settings. This
      article reports an efficiency analysis of health care in state correctional
      institutions (SCIs) in a single, mid-Atlantic state from 2003 to 2006. A two
      stage data envelopment analysis was used to estimate the technical efficiency of
      prison health care and determine inmate and institutional characteristics that
      were associated with efficiency. Our output variable was the number of infirmary
      inpatient days for each year of study. The input variable for the first stage was
      the sum of personnel medical staff costs and other medical operating costs. SCIs
      with more white prisoners, older prisoners, and higher proportions of inmates
      with parole violations were significantly less efficient in their provision of
      health care than other SCIs. There were no SCI characteristics that were
      predictive of efficiency. These results suggest that healthcare efficiency in
      corrections may decline as the prison population continues to age. 

PMID- 25987846
TI  - The effects of serum from prostate cancer patients with elevated body mass index
      on prostate cancer cells in vitro.
AB  - We examined whether serum from obese, compared to non-obese, PCa (prostate
      cancer) patients creates a growth-enhancing tumor micro-environment in vitro.
      Serum from 80 subjects was divided into four groups: normal weight men with and
      without PCa and overweight/obese men with and without PCa. Cell proliferation,
      migration, and invasion were measured in LNCaP, and PC3 cells treated with
      patient serum were obtained from the above groups. The results reveal that
      proliferation of LNCaP cells was significantly (P = 0.05) greater with serum from
      non-obese (mean = 1.26 +/- 0.20) compared to that from obese patients (mean =
      1.16 +/- 0.19). Serum from obese PCa patients compared to non-obese PCa patients
      induced significantly greater amounts of cell migration (P < 0.01) in PC3 cells.
      Serum from obese patients induced significantly (P < 0.01) lower amounts of cell
      invasion (mean = 8.2 +/- 4.5) compared to non-obese patients (mean = 18.1 +/-
      5.0) when treated on PC3 cells. Serum TNF-alpha (tumor necrosis factor alpha)
      levels correlated with LNCaP cell proliferation in vitro in non-obese PCa (P <
      0.01) and non-obese control groups (P = 0.05). All statistical calculations
      controlled for age, since the PCa patient groups were significantly older than
      the control groups (P < 0.01). In conclusion, serum from obese PCa patients
      induced greater PCa cell migration and lower cell proliferation and invasion in
      vitro. 

PMID- 25987847
TI  - Choline and Fructooligosaccharide: Non-alcoholic Fatty Liver Disease, Cardiac Fat
      Deposition, and Oxidative Stress Markers.
AB  - This study investigates the treatment of non-alcoholic fatty liver disease
      (NAFLD) in rats with choline and fructooligosaccharide (FOS). The healthy control
      group received standard diet. The other three groups consisted of animals with
      NAFLD. Group Estr received standard diet; group Echo received standard diet plus
      choline (3 g/100 g diet); and group Efos received standard diet plus FOS (10
      g/100 g diet). Food intake, weight, urinary nitrogen, urinary ammonia, total
      cholesterol, serum triacylglyceride, liver and heart weights, tissue nitrogen,
      tissue fat, vitamin E, TBARS, and reduced glutathione (GSH) were measured in
      hepatic and heart tissue. Choline and FOS treatments resulted in total mean fat
      reduction in liver and heart tissue of 0.2 and 1.7 g, respectively. Both
      treatments were equally effective in reducing hepatic and cardiac steatosis.
      There were no differences in the TBARS level among experimental and control
      groups, indicating that the proposed treatments had no added protection against
      free radicals. While all experimental groups had increased vitamin E and GSH
      levels, choline treatment led to a significant increase compared to control. 

PMID- 25987848
TI  - Method for Evaluation of the Requirements of B-group Vitamins Using Tryptophan
      Metabolites in Human Urine.
AB  - Tryptophan metabolism is directly involved with B-group vitamins such as vitamin
      B2, niacin, and vitamin B6, and indirectly with vitamin B1 and pantothenic acid.
      We evaluated the validity of requirements of B-group vitamins set by the Dietary
      Reference Intakes for the Japanese (DRI-J). We investigated the fate of dietary
      tryptophan in 10 Japanese adult men who ate the same diet based on DRI-J during a
      4-week study. Vitamin mixtures were administered based on the amounts in the
      basal diet during weeks 2, 3, and 4. Daily urine samples were collected eight
      times (days 1 and 5 in each week). Administration of vitamin mixtures had no
      effect on tryptophan metabolites such as anthranilic acid, kynurenic acid,
      xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid within
      individuals. Surplus administration of B-group vitamins against DRI-J
      requirements did not elicit beneficial effects on tryptophan metabolism. Our
      findings supported the requirements of B-group vitamins set by the DRI-J. 

PMID- 25987849
TI  - Strumpellin and Spartin, Hereditary Spastic Paraplegia Proteins, are Binding
      Partners.
AB  - Hereditary spastic paraplegia (HSP) is one of the most heterogeneous
      neurodegenerative diseases with more than 50 identified genes causing a
      relatively stereotypical phenotypic presentation. Recent studies of HSP
      pathogenesis have suggested the existence of shared biochemical pathways that are
      crucial for axonal maintenance and degeneration. We explored possible
      interactions of several proteins associated with this condition. Here we report
      interactions of endogenous and overexpressed strumpellin with another HSP
      associated protein, spartin. This biochemical interaction does not appear to be a
      part of the Wiskott-Aldrich syndrome protein and Scar homologue (WASH) complex
      because spartin is not co-immunoprecipitated with WASH1 protein. The spartin
      strumpellin association does not require the presence of the microtubule
      interacting and trafficking domain of spartin. Over-expression of mutant forms of
      strumpellin with the introduced HSP-causing mutations does not alter the
      colocalization of these two proteins. Knockdown of strumpellin in cultured
      cortical rat neurons interferes with development of neuronal branching and
      results in reduced expression of endogenous spartin. Proteosomal inhibition
      stabilized the levels of spartin and WASH1 proteins, supporting increased spartin
      degradation in the absence of strumpellin. 

PMID- 25987850
TI  - Memory impairment and reduced exploratory behavior in mice after administration
      of systemic morphine.
AB  - In the present study, the effects of morphine were examined on tests of spatial
      memory, object exploration, locomotion, and anxiety in male ICR mice.
      Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a
      significant decrease in Y-maze alternations compared to saline vehicle-treated
      mice. The reduced Y-maze alternations induced by morphine were completely blocked
      by naloxone (15 mg/kg) or beta-funaltrexamine (5 mg/kg) but not by
      norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the
      morphine-induced spatial memory impairment was mediated predominantly by MU
      opioid receptors (MOPs). Significant spatial memory retrieval impairments were
      observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg)
      or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone.
      Reduced exploratory time was observed in mice after administration of morphine
      (15 mg/kg), in a novel-object exploration test, without any changes in locomotor
      activity. No anxiolytic-like behavior was observed in morphine-treated mice in
      the elevated plus maze. A significant reduction in buried marbles was observed in
      morphine-treated mice measured in the marble-burying test, which was blocked by
      naloxone. These observations suggest that morphine induces impairments in spatial
      short-term memory and retrieval, and reduces exploratory behavior, but that these
      effects are not because of overall changes in locomotion or anxiety. 

PMID- 25987852
TI  - Surgical outcome and complications of nasal septal perforation repair with
      temporal fascia and periosteal grafts.
AB  - AIMS: Surgical treatment of nasal septal perforation remains a challenging field
      of rhinology. A large variety of techniques and grafts with promising results
      have been introduced for perforation repair. However, the use of fascia or fascia
      with periosteum has not been previously evaluated for a large sample of patients.
      METHODS: During the years 2007-2014, 105 operations were performed and 98
      patients were treated for nasal septal perforation at the Department of
      Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital,
      Helsinki, Finland. We performed a retrospective review of closure rates and
      complications. Follow-up time ranged from 1 to 62 months. RESULTS: Bleeding was
      the most common early complication (9%), followed by postoperative infection (5%)
      in the whole series. Our main technique, bipedicled advancement flaps with fascia
      or fascia and periosteum, was performed for 81 patients. We obtained successful
      closure in 78% of these patients with this operative technique and the rate
      increased to 86% during the last 3 years of the study period. CONCLUSIONS:
      Perforation repair with temporal fascia or fascia with periosteum requiring only
      one donor site seems to be a reliable option for nasal septal perforation repair.

PMID- 25987851
TI  - Pre-exposure prophylaxis for sexually-acquired HIV risk management: a review.
AB  - Despite significant efforts, the rate of new HIV infections worldwide remains
      unacceptably high, highlighting the need for new HIV prevention strategies. HIV
      pre-exposure prophylaxis (PrEP) is a new approach that involves the ongoing use
      of antiretroviral medications by HIV-negative individuals to reduce the risk of
      HIV infection. The use of daily tenofovir/emtricitabine as oral PrEP was found to
      be effective in multiple placebo-controlled clinical trials and approved by the
      United States Food and Drug Administration. In addition, the Centers for Disease
      Control and Prevention in the United States and the World Health Organization
      have both released guidelines recommending the offer of oral PrEP to high-risk
      populations. The scale-up of PrEP is underway, but several implementation
      questions remain unanswered. Demonstration projects and open-label extensions of
      placebo-controlled trials are ongoing and hope to contribute to our understanding
      of PrEP use and delivery outside the randomized controlled trial setting.
      Evidence is beginning to emerge from these open-label studies and will be
      critical for guiding PrEP scale-up. Outside of such studies, PrEP uptake has been
      slow and several client- and provider-related barriers are limiting uptake.
      Maximizing the public health impact of PrEP will require rollout to be combined
      with interventions to promote uptake, support adherence, and prevent increases in
      risk behavior. Additional PrEP strategies are currently under investigation in
      placebo-controlled clinical trials and may be available in the future. 

PMID- 25987853
TI  - The Relationship between Thyroid Function and Depressive Symptoms-the FIN-D2D
      Population-Based Study.
AB  - The association between thyroid function and depression is controversial. Both
      conditions express many similar symptoms, but the studies done give conflicting
      results. This study draws on a random, population-based sample of 4500 subjects
      aged 45-75 years old from Finland. The basic clinical study was done in 2007 for
      1396 men and 1500 women (64% participation rate). Thyroid stimulating hormone
      (TSH), free thyroxine (F-T4), and free triiodothyronine (F-T3) were measured in
      2013 from frozen samples. The 21-item Beck Depression Inventory (BDI-21) was
      applied to assess depressive symptoms (score >=10 points). The prevalence of
      depressive symptoms was 17.5% in women and 12.5% in men. In women, the mean
      levels of TSH, F-T4, and F-T3 without depressive symptoms vs. with the presence
      of depressive symptoms were 1.92/1.97 mU/L, 13.1/13.1 pmol/L, and 3.91/3.87
      pmol/L (NS), respectively. In men, the levels were 1.87/1.94 mU/L, 13.5/13.7
      pmol/L, and 4.18/4.12 pmol/L (NS), respectively. In multiple regression analysis,
      TSH had no relationship to BDI-21 total score. We found no association between
      depressive symptoms and thyroid values. 

PMID- 25987854
TI  - Predictors of abnormal bone mass density in adult patients with homozygous sickle
      cell disease.
AB  - BACKGROUND: Adult patients with sickle-cell disease (SCD) often have multiple
      bone compactions causing tissue hypoxia and osteonecrosis. The impact on bone
      abnormalities lesion detected by bone mass density is not well defined. AIM: The
      study is a cross sectional, perspective was designed to assess the prevalence of
      abnormal BMD in adult Bahraini patients with SCD and to assess the predictive
      risk of different metabolic variables such as serum level of vitamin D3,
      testosterone, and parathyroid hormone in addition to lactate dehydrogenase (LDH),
      hemoglobin (Hb), and reticulocyte count for the development of abnormal bone
      density on dual X-ray absorptiometry (DXA) scan. METHOD: The study was conducted
      over the period of 12 months from first of January 2012 to end of December 2012.
      All patients were evaluated clinically for severity of SCD and abnormal bone mass
      density (BMD) using DXA scan. Blood samples were withdrawn for measuring the
      serum level of vitamin D3, testosterone, and parathyroid hormone in addition to
      Hb, LDH, and reticulocyte count. Multiple logistic regression analysis was used
      to assess risk prediction of different variables for the development of abnormal
      BMD on DXA with T-score <=-2.5 standard deviation (SD). RESULTS: The study
      included Bahraini patients with SCD (n = 55, age 29.24 +/- 9.47 years, male 60%
      and female 40%) compared with an age-matched healthy control group (n = 55, age
      28.82 +/- 8.64 years, with 62% male and 38% female). Of the 55 patients with SCD
      compared with the control group, there were 33 (58%) patients with low BMD and 2
      (3%) in the control. Among the 33 patients with SCD and with low BMD, there were
      20 (36%) with osteoporosis (T-score of <=-2.5 SD) and 13 (24%) with osteopenia (T
      score of <-1 to -2.5 SD). The most affected site of low BMD was lumbar spine
      (55%), followed by the radius (30%) and neck of the femur (15%). SCD patients
      with osteoporosis compared with the healthy subjects had significantly lower body
      surface area (BSA, m(2)) of 1.4 +/- 0.3 vs. 1.63 +/- 0.5 BMI, low level of
      vitamin D3 of 21.11 +/- 6.95 ng/mL vs. 46.2 +/- 15.19 (P < 0.001), lower
      testosterone level of 1.34 +/- 0.54 vs. 2.18 +/- 0.56 ng/mL (P < 0.001), higher
      reticulocyte count (P < 0.001), and higher LDH level (P < 0.001). The low serum
      level of vitamin D3 (<20 ng/mL) and low testosterone of <0.9 ng/mL had risk
      prediction (odds ratio) of 1.14 and 1.2, respectively, for abnormal BMD in SCD.
      In the risk prediction of other variables of parathormone (PTH), LDH, and
      reticulocyte, were not significant. CONCLUSION: The prevalence of abnormal bone
      mass density (BMD) is high (60%) in Bahraini patients with SCD. There is
      significant low serum level of vitamin D3 and low testosterone hormone in those
      with very low bone mass density (BMD) (osteoporosis and T-score <-2.5). The low
      serum level of vitamin D3 (<20 ng/mL) and low testosterone of <0.9 ng/mL had risk
      prediction (odds ratio) of 1.14 and 1.2, respectively, for abnormal BMD in SCD.

PMID- 25987855
TI  - Functions of Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma) in
      Gynecologic Disorders.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of a
      class of nuclear hormone receptors intimately involved in the regulation of
      expression of myriad genes that regulate energy metabolism, cell differentiation,
      apoptosis, and inflammation. Although originally discovered as a pivotal
      regulator of adipocyte differentiation, the roles that PPARgamma plays in
      gynecological disorders are still unknown. There are a number of studies on the
      functions of PPARgamma and its agonists in gynecological disorders. In this mini
      review, we provide a brief summary of the advances in recent years. 

PMID- 25987856
TI  - Comparison of the blood and lymphatic microvessel density of pleomorphic adenoma
      and Basal cell adenoma.
AB  - BACKGROUND: Pleomorphic adenoma (PA) is the most common tumor of the salivary
      gland, while basal cell adenoma (BCA) is an uncommon neoplasm. Blood and
      lymphatic vessels are crucial for tumor metabolism. The aim of this study was to
      compare the blood and lymphatic vascular density and vascular and endothelial
      growth factor (VEGF) expression in PA and BCA tumors. In addition, cell
      proliferation was evaluated in these tumors. METHODS: Blood and lymphatic vessel
      content, VEGF expression, and cell proliferation were analyzed in 30 cases of PA
      and 13 cases of BCA by immu-nohistochemistry using antibodies for CD34, CD105, D2
      40, VEGF, and Mcm-2. RESULTS: Regarding CD34 and CD105 expression, PA
      demonstrated a high vascularity and a low number of positive vessels,
      respectively. D2-40-positive lymphatic vessels were mainly located in the tumor
      capsules, with small intratumoral lymphatic vessels observed occasionally. VEGF
      expression revealed a remarkably heterogeneous immunoreactivity, alternating from
      weak or negative to positive or intense. BCA presented significantly higher CD34,
      CD34, CD105, D2-40, and VEGF expression compared to PA. No significant difference
      was found in cell proliferation between the tumors. CONCLUSION: Although PA and
      BCA are considered part of the same spectrum of differentiation, this study
      showed that the blood and lymphatic vascularization of these tumors is different.

PMID- 25987857
TI  - The effects of celecoxib or naproxen on blood pressure in pediatric patients with
      juvenile idiopathic arthritis.
AB  - BACKGROUND: Selective and nonselective nonsteroidal anti-inflammatory drugs
      (NSAIDs) are indicated for the treatment of juvenile idiopathic arthritis (JIA).
      However, the effect of NSAIDs on blood pressure (BP) in children has not been
      rigorously examined. METHODS: In this randomized, double-blind, multicenter,
      active-controlled, 6-week trial, the safety and efficacy of celecoxib (50 mg
      twice daily [bid] or 100 mg bid) or naproxen (7.5 mg/kg bid) was evaluated in
      patients aged 2-17 years with JIA. RESULTS: The least squares (LS) mean
      difference (celecoxib - naproxen) in change from baseline to week 6/final visit
      in systolic BP was 1.10 (90% confidence interval, -0.56, 2.76). No significant LS
      mean differences in diastolic BP relative to baseline were reported. Treatment
      emergent adverse events occurred in 48% of patients in each treatment group.
      CONCLUSION: Both celecoxib and naproxen had no impact on BP, and both treatments
      had comparable safety profiles. Celecoxib, or naproxen, could be seen as suitable
      treatment options for pediatric patients with JIA.

PMID- 25987858
TI  - Why do we need a diagnosis? Maybe a syndrome is enough?
AB  - The recent publication of the Diagnostic and Statistical Manual of Mental
      Disorders 5.1 by the American Psychiatric Association, and the continuing work of
      the World Health Organization on the 11th revision of the International
      Classification of Diseases raises once more the question of the need for, the
      use, and the usefulness of diagnosis in psychiatry The fact that, despite
      significant advances of science, we are still uncertain about the causes and
      pathogenesis of mental disorders seems to support the notion that it would be
      better to use syndromes instead of diagnoses, or go even further and describe
      mental states in health and disease by a series of ratings on key dimensions of
      mental functioning. Another option that has also received some backing is the
      presentation of the universe of mental illness by a series of disease prototypes
      which, it is argued, would be particularly attractive to practising clinicians.
      The paper discusses these issues and ends by supporting the use of different ways
      of presenting mental illness, depending on the purpose of the description. 

PMID- 25987859
TI  - Focus on psychosis.
AB  - The concept of psychosis has been shaped by traditions in the concepts of mental
      disorders during the last 170 years. The term "psychosis" still lacks a unified
      definition, but denotes a clinical construct composed of several symptoms.
      Delusions, hallucinations, and thought disorders are the core clinical features.
      The search for a common denominator of psychotic symptoms points toward
      combinations of neuropsychological mechanisms resulting in reality distortion. To
      advance the elucidation of the causes and the pathophysiology of the symptoms of
      psychosis, a deconstruction of the term into its component symptoms is therefore
      warranted. Current research is dealing with the delineation from "normality", the
      genetic underpinnings, and the causes and pathophysiology of the symptoms of
      psychosis. 

PMID- 25987860
TI  - Descriptive psychopathology, phenomenology, and the legacy of Karl Jaspers.
AB  - With his early publications (1910-1913), Karl Jaspers created a comprehensive
      methodological arsenal for psychiatry, thus laying the foundation for descriptive
      psychopathology. Following Edmund Husserl, the founder of philosophical
      phenomenology, Jaspers introduced phenomenology into psychopathology as "static
      understanding," ie, the unprejudiced intuitive reproduction (Vergegenwartigung)
      and description of conscious phenomena. In a longitudinal perspective, "genetic
      understanding" based on empathy reveals how mental phenomena arise from mental
      phenomena. Severance in understanding of, or alienation from, meaningful
      connections is seen as indicating illness or transition of a natural development
      into a somatic process. Jaspers opted for philosophy early. After three terms of
      law, he switched to studying medicine, came to psychopathology after very little
      training in psychiatry; to psychology without ever studying psychology; and to a
      chair in philosophy without ever studying philosophy. In the fourth and
      subsequent editions of his General Psychopathology, imbued by his existential
      philosophy, Jaspers partly abandoned the descriptive method. 

PMID- 25987861
TI  - The Kraepelinian tradition.
AB  - Emil Kraepelin (1856-1926) was an influential figure in the history of psychiatry
      as a clinical science. This paper, after briefly presenting his biography,
      discusses the conceptual foundations of his concept of mental illness and follows
      this line of thought through to late 20th-century "Neo-Kraepelinianism,"
      including recent criticism, particularly of the nosological dichotomy of
      endogenous psychoses. Throughout his professional life, Kraepelin put emphasis on
      establishing psychiatry as a clinical science with a strong empirical background.
      He preferred pragmatic attitudes and arguments, thus underestimating the
      philosophical presuppositions of his work. As for nosology, his central
      hypothesis is the existence and scientific accessibility of "natural disease
      entities" ("naturliche Krankheitseinheiten") in psychiatry. Notwithstanding
      contemporary criticism that he commented upon, this concept stayed at the very
      center of Kraepelin's thinking, and therefore profoundly shaped his clinical
      nosology. 

PMID- 25987862
TI  - Eugen Bleuler's schizophrenia--a modern perspective.
AB  - The introduction of the term and concept schizophrenia earned its inventor, Swiss
      psychiatrist Eugen Bleuler, worldwide fame. Prompted by the rejection of the main
      principle of Kraepelinian nosology, namely prognosis, Bleuler's belief in the
      clinical unity of what Kraepelin had described as dementia praecox required him
      to search for alternative characterizing features that would allow scientific
      description and classification. This led him to consider psychological, and to a
      lesser degree, social factors alongside an assumed underlying neurobiological
      disease process as constitutive of what he then termed schizophrenia, thus making
      him an early proponent of a bio-psycho-social understanding of mental illness.
      Reviewing Bleuler's conception of schizophrenia against the background of his
      overall clinical and theoretical work, this paper provides a critical overview of
      Bleuler's key nosological principles and links his work with present-day debates
      about naturalism, essentialism, and stigma. 

PMID- 25987863
TI  - French perspectives on psychiatric classification.
AB  - This article reviews the role of the French schools in the development of
      psychiatric nosology. Boissier de Sauvages published the first French treatise on
      medical nosology in 1763. Until the 1880s, French schools held a pre-eminent
      position in the development of psychiatric concepts. From the 1880s until World
      War I, German-speaking schools exerted the most influence, featuring the work of
      major figures such as Emil Kraepelin and Eugen Bleuler. French schools were
      probably hampered by excessive administrative and cultural centralization.
      Between the 1880s and the 1930s, French schools developed diagnostic categories
      that set them apart from international classifications. The main examples are
      Bouffee Delirante, and the complex set of chronic delusional psychoses (CDPs),
      including chronic hallucinatory psychosis. CDPs were distinguished from
      schizophrenia by the lack of cognitive deterioration during evolution. Modern
      French psychiatry is now coming into line with international classification, such
      as DSM-5 and the upcoming ICD-11. 

PMID- 25987864
TI  - The history of nosology and the rise of the Diagnostic and Statistical Manual of
      Mental Disorders.
AB  - The current Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 arose
      from a tradition filled with haphazard science and politically driven choices.
      The nosology of modern psychiatry began with the German classifiers of the late
      19th century, especially Emil Kraepelin. Psychoanalysis then blotted out the
      classificatory vision for the next half-century, and most of this European
      psychopathological science failed to cross the Atlantic. The DSM series was a
      homegrown American product, beginning with Medical 203 in 1945, then guided by
      psychoanalytic insights through DSM-I in 1952 and DSM-II in 1968. In 1980, DSM
      III represented a massive "turning of the page" in nosology, and it had the
      effect of steering psychoanalysis toward the exit in psychiatry and the beginning
      of a reconciliation of psychiatry with the rest of medicine. With the advent of
      DSM-5, however, questions are starting to be asked about whether this massive
      venture is on the right track. 

PMID- 25987865
TI  - Genetic and genomic analyses as a basis for new diagnostic nosologies.
AB  - For schizophrenia, bipolar disorder, and autism, clinical descriptions are
      precise and reliable, but there is great overlap among diagnoses in associated
      genetic polymorphisms and rare variants, treatment response, and other
      phenomenological findings such as brain imaging. It is widely hoped that new
      diagnostic categories can be developed which are more precise and predictive of
      important features of illness, particularly response to pharmacological agents.
      It is the intent of this paper to describe the diagnostic implications of some
      current genetic findings, and to describe how the genetic associations with
      diagnosis may be teased apart into new associations with biologically coherent
      diagnostic entities and scales, based on the various functional aspects of the
      associated genes and functional genomic data. 

PMID- 25987866
TI  - A knowledge network for a dynamic taxonomy of psychiatric disease.
AB  - Current taxonomic approaches in medicine and psychiatry are limited in validity
      and utility. They do serve simple communication purposes for medical coding,
      teaching, and reimbursement, but they are not suited for the modern era with its
      rapid explosion of knowledge from the "omics" revolution. The National Academy of
      Sciences published a report entitled Toward Precision Medicine: Building a
      Knowledge Network for Biomedical Research and a New Taxonomy of Disease. The
      authors advocate a new taxonomy that would integrate molecular data, clinical
      data, and health outcomes in a dynamic, iterative fashion, bringing together
      research, public health, and health-care delivery with the interlinked goals of
      advancing our understanding of disease pathogenesis and thereby improving health.
      As the need for an information hub and a knowledge network with a dynamic
      taxonomy based on integration of clinical and research data is vital, and timely,
      this proposal merits consideration. 

PMID- 25987867
TI  - Research Domain Criteria: toward future psychiatric nosologies.
AB  - The Research Domain Criteria (RDoC) project was initiated by the National
      Institute of Mental Health (NIMH) in early 2009 as the implementation of Goal 1.4
      of its just-issued strategic plan. In keeping with the NIMH mission, to
      "transform the understanding and treatment of mental illnesses through basic and
      clinical research," RDoC was explicitly conceived as a research-related
      initiative. The statement of the relevant goal in the strategic plan reads:
      "Develop, for research purposes, new ways of classifying mental disorders based
      on dimensions of observable behavior and neurobiological measures." Due to the
      novel approach that RDoC takes to conceptualizing and studying mental disorders,
      it has received widespread attention, well beyond the borders of the immediate
      research community. This review discusses the rationale for the experimental
      framework that RDoC has adopted, and its implications for the nosology of mental
      disorders in the future. 

PMID- 25987868
TI  - ZooKeys 500: traditions and innovations hand-in-hand servicing our taxonomic
      community.

PMID- 25987869
TI  - Terry L. Erwin: She Had a Black Eye and in Her Arm She Held a Skunk: Re-published
      from "American Entomologist" Vol. 61 (I) on the occasion of ZooKeys 500.

PMID- 25987871
TI  - A new gall crab species (Brachyura, Cryptochiridae) associated with the free
      living coral Trachyphylliageoffroyi (Scleractinia, Merulinidae).
AB  - A new species of gall crab is described from the free-living stony coral
      Trachyphylliageoffroyi. Specimens were collected during field work in Lembeh
      Strait (Indonesia) and off Kudat (Malaysian Borneo). This new species, here named
      Lithoscaptussemperi sp. n., is the ninth species assigned to the genus. It can be
      separated from its congeners by not having the internal orbital angle extending
      beyond the external orbital angle, and by the stout female P2 merus with
      prominent distomesial projection. In addition, the carapace surface appears
      smooth, despite having small tubercles on the anterior half, and is without
      noticeable spines, other than those on the frontal margin. The distinctive
      carapace pattern in life is a diagnostic character in male specimens. 

PMID- 25987870
TI  - A large 28S rDNA-based phylogeny confirms the limitations of established
      morphological characters for classification of proteocephalidean tapeworms
      (Platyhelminthes, Cestoda).
AB  - Proteocephalidean tapeworms form a diverse group of parasites currently known
      from 315 valid species. Most of the diversity of adult proteocephalideans can be
      found in freshwater fishes (predominantly catfishes), a large proportion infects
      reptiles, but only a few infect amphibians, and a single species has been found
      to parasitize possums. Although they have a cosmopolitan distribution, a large
      proportion of taxa are exclusively found in South America. We analyzed the
      largest proteocephalidean cestode molecular dataset to date comprising more than
      100 species (30 new), including representatives from 54 genera (80%) and all
      subfamilies, thus significantly improving upon previous works to develop a
      molecular phylogeny for the group. The Old World origin of proteocephalideans is
      confirmed, with their more recent expansion in South America. The earliest
      diverging lineages are composed of Acanthotaeniinae and Gangesiinae but most of
      the presently recognized subfamilies (and genera) appear not to be monophyletic;
      a deep systematic reorganization of the order is thus needed and the present
      subfamilial system should be abandoned. The main characters on which the
      classical systematics of the group has been built, such as scolex morphology or
      relative position of genital organs in relation to the longitudinal musculature,
      are of limited value, as demonstrated by the very weak support for
      morphologically-defined subfamilies. However, new characters, such as the pattern
      of uterus development, relative ovary size, and egg structure have been
      identified, which may be useful in defining phylogenetically well-supported
      subgroups. A strongly supported lineage infecting various snakes from a wide
      geographical distribution was found. Although several improvements over previous
      works regarding phylogenetic resolution and taxon coverage were achieved in this
      study, the major polytomy in our tree, composed largely of siluriform parasites
      from the Neotropics, remained unresolved and possibly reflects a rapid radiation.
      The genus Spasskyellina Freze, 1965 is resurrected for three species of
      Monticellia bearing spinitriches on the margins of their suckers. 

PMID- 25987872
TI  - A remarkable new species of Alloscorpiops Vachon, 1980 from a cave in Vietnam
      (Scorpiones, Euscorpiidae, Scorpiopinae).
AB  - Among the genera of the subfamily Scorpiopinae Kraepelin, 1905 Alloscorpiops
      remains rather discrete. Only recently new species were added to this genus,
      increasing its number from two to five. Therefore, species of Alloscorpiops
      remain rare. One remarkable new species, Alloscorpiopstroglodytes sp. n., is
      described on the basis of a single male specimen collected inside a cave from
      Song Thanh Nature Reserve, Cha Vanh Commune, Nam Giang District in Vietnam. The
      new species presents most features exhibited by scorpions of the genus
      Alloscorpiops, but it is characterized by reduced size, slender body and
      elongated pedipalps. This new scorpion taxon represents the third species of
      Scorpiopinae discovered in a cave system, and may be another endemic element in
      the fauna of Vietnam. 

PMID- 25987873
TI  - Two new species of the Liolaemuselongatus-kriegi complex (Iguania, Liolaemidae)
      from Andean highlands of southern Chile.
AB  - The elongatus-kriegi complex is one of the most diverse clades of the Liolaemus
      (sensu stricto) subgenus of lizards. There are currently 29 species recognized in
      this group distributed between Chile and Argentina. Based on molecular evidence,
      there seem to be five main clades nested within this complex: the elongatus,
      leopardinus, kriegi, petrophilus and punmahuida clades. Liolaemusbuergeri and
      Liolaemuskriegi, both of the kriegi clade, were believed to inhabit the
      surroundings of the Laja Lagoon, in the Biobio Region of Chile. Moreover, this
      Chilean population of Liolaemuskriegi was recently recognized as an undescribed
      taxon called "Liolaemus sp. A" based on molecular phylogenetics. In this work, we
      studied these two populations of the Laja Lagoon and provided the morphological
      diagnosis to describe them as two new species: Liolaemusscorialis sp. n. and
      Liolaemuszabalai sp. n., previously considered Liolaemusbuergeri and
      "Liolaemuskriegi/Liolaemus sp. A" respectively. Additionally, we identified
      another population of Liolaemusscorialis in the vicinity of La Mula Lagoon in the
      Araucania Region of Chile. Liolaemusscorialis differs from almost all of the
      species of the elongatus-kriegi complex by its considerably smaller size.
      Nevertheless, without molecular data we cannot assign it to any particular
      subclade. Liolaemuszabalai belongs to the kriegi clade based on published
      molecular phylogenies. Finally, we provide some natural history data on both
      species and we document for the first time the presence of Liolaemusneuquensis in
      Chile from a museum specimen from La Mula Lagoon. 

PMID- 25987874
TI  - A taxonomic review of Aramidescajaneus (Aves, Gruiformes, Rallidae) with notes on
      morphological variation in other species of the genus.
AB  - The taxonomy of the polytypic and wide-ranging Gray-necked Wood-rail,
      Aramidescajaneus is reviewed, based on external morphology and voice. Throughout
      its distribution, there is extensive plumage variation, much of it taxonomically
      uninformative. However, through three informative plumage characters, as well as
      morphometric and vocal variation, three phylogenetic species were identified
      within what is today known as Aramidescajaneus, all of which already had
      available names: Aramidesalbiventris Lawrence, 1868, from southern Mexico to
      northeastern Costa Rica, Aramidescajaneus (Statius Muller, 1776) (sensu stricto),
      from southwestern Costa Rica to Argentina, and Aramidesavicenniae Stotz, 1992,
      from a small section of the coast of southeastern Brazil. Aramidesalbiventris
      presents extensive plumage variation, but with no geographic structure. The song
      of Aramidescajaneus and Aramidesavicenniae is strikingly and completely different
      from the song of Aramidesalbiventris. A previously unnoticed parapatric pattern
      of distribution of Aramidescajaneus and its congener Aramidessaracura in
      southeastern Brazil is described, and we clarify that the name
      Aramidesplumbeicollis, included in the synonymy of Aramidesalbiventris, was first
      made available in 1892, rather than in 1888 as is widely referred. In addition,
      plumage variation in Aramidesypecaha, Aramideswolfi, and Aramidesmangle is
      discussed. 

PMID- 25987875
TI  - Can whole-drawer images measure up? A reply to Johnson et al. (2013)?
AB  - Johnson et al. (2013) found that morphometric measurements of dragonfly wings
      taken from actual specimens and measurements taken from whole-drawer images of
      those specimens were equally accurate. We do not believe that their conclusions
      are justified by their data and analysis. Our reasons are, first, that their
      study was constrained in ways that restrict the generalisability of their
      results, but second, and of far greater significance, their statistical approach
      was entirely unsuited to their data and their results misled them to erroneous
      conclusions. We offer an alternative analysis of their data as published. Our
      reanalysis demonstrates, contra Johnson et al., that measurements from scanned
      images are not a reliable substitute for direct measurement. 

PMID- 25987877
TI  - Molecular data for Crenavolva species (Gastropoda, Ovulidae) reveals the synonymy
      of C.chiapponii.
AB  - During fieldwork in Indonesia and Malaysia, eight lots containing 33 specimens
      belonging to the genus Crenavolva (Ovulidae) were collected. Species were
      initially identified as Crenavolvaaureola, Crenavolvachiapponii,
      Crenavolvastriatula and Crenavolvatrailli, respectively. For Crenavolvachiapponii
      this is the second record. In contrast to the ecological data available from the
      original description of this species, it was found in shallow water on a
      gorgonian host coral, i.e. Acanthogorgia sp. A molecular analysis based on COI
      and 16S mtDNA markers, including sequence data obtained from GenBank, showed that
      Crenavolvachiapponii should be considered a junior synonym of Crenavolvaaureola
      and that previously identified ovulid specimens are probably misidentified. 

PMID- 25987876
TI  - On the identity of Chamaedrilusglandulosus (Michaelsen, 1888) (Clitellata,
      Enchytraeidae), with the description of a new species.
AB  - The taxonomy of Chamaedrilusglandulosus (Michaelsen, 1888) s. l., most commonly
      known previously as Cognettiaglandulosa, is revised. A recent molecular
      systematic study has shown that this taxon harbours two cryptic, but genetically
      well separated lineages, each warranting species status. In this study these two
      lineages are scrutinized morphologically, on the basis of Michaelsen's type
      material as well as newly collected specimens from Central and Northern Europe.
      Chamaedrilusglandulosus s. s. is redescribed and Chamaedrilusvarisetosus sp. n.
      is recognized as new to science. The two species are morphologically very
      similar, differing mainly in size, but seem to prefer different habitats, with
      Chamaedrilusglandulosus being a larger aquatic species, and
      Chamaedrilusvarisetosus being smaller and mainly found in moist to wet soil. 

PMID- 25987878
TI  - A review of Bornean Micronectidae (Hemiptera, Heteroptera, Nepomorpha) with
      descriptions of two new species from Sabah, Malaysia.
AB  - Previous research of Bornean Micronectidae Jaczewski, 1924 (pygmy water boatmen)
      is summarized based on the data from the literature and recent work. All the
      Bornean micronectids belong to the genus Micronecta Kirkaldy, 1897. Descriptions
      or redescriptions and a key to the eight species, which have so far been found in
      Borneo are presented, namely Micronectadecorata Lundblad, 1933,
      Micronectaludibunda Breddin, 1905, Micronectaliewi sp. n., Micronectalakimi sp.
      n., Micronectalumutensis Chen, Nieser & Lansbury, 2008, Micronectaskutalis Nieser
      & Chen, 1999, Micronectakymatista Nieser & Chen, 1999) and
      Micronectaquadristrigata Breddin, 1905. The synonyms are indicated under each
      species. To facilitate identification, illustrations and habitus photos are
      provided. The faunistic components of Micronectidae in Borneo are discussed from
      a zoogeographic point of view. 

PMID- 25987879
TI  - Molecular phylogeny of the genus Dicronocephalus (Coleoptera, Scarabaeidae,
      Cetoniinae) based on mtCOI and 16S rRNA genes.
AB  - The seven species belonging to the genus Dicronocephalus are a very interesting
      group with a unique appearance and distinct sexual dimorphism. Only one species
      among them, Dicronocephalusadamsi, has been known in the Korean fauna. This
      species is recognized as having a wide distribution from Tibet to Korean
      Peninsula and is currently represented by two subspecies that have separated
      geographical ranges. The phylogenetic relationships of Dicronocephalusadamsi were
      still unclear. The phylogeny of Dicronocephalus is reconstructed with a
      phylogenetic study of five species including four subspecies based on a molecular
      approach using mitochondrial COI and 16S rRNA genes. Our results are compared
      with the results obtained by previous authors based on morphological characters.
      They show that the tested taxa are divided into two major clades. Clade A
      consists of two species (Dicronocephalusadamsi + Dicranocephalusyui) and Clade B
      includes the others (Dicronocephalusdabryi + Dicranocephalusuenoi +
      Dicranocephaluswallichii). This result generally supports Kurosawa's proposal
      except that Dicronocephalusdabryi and Dicranocephalusuenoi are newly recognized
      as members of a monophyletic group. We propose that Dicronocephalusadamsidrumonti
      is a junior subjective synonym of Dicronocephalusadamsiadamsi. These results show
      that three members of the Dicranocephaluswallichii group should be treated as
      species rather than subspecies. However, further research including analyses of
      different genetic markers is needed to reconfirm our results. 

PMID- 25987880
TI  - Revised and annotated checklist of aquatic and semi-aquatic Heteroptera of
      Hungary with comments on biodiversity patterns.
AB  - A basic knowledge of regional faunas is necessary to follow the changes in
      macroinvertebrate communities caused by environmental influences and climatic
      trends in the future. We collected all the available data on water bugs in
      Hungary using an inventory method, a UTM grid based database was built, and
      Jackknife richness estimates and species accumulation curves were calculated.
      Fauna compositions were compared among Central-European states. As a result, an
      updated and annotated checklist for Hungary is provided, containing 58 species in
      21 genera and 12 families. A total 66.8% of the total UTM 10 * 10 km squares in
      Hungary possess faunistic data for water bugs. The species number in grid cells
      numbered from 0 to 42, and their diversity patterns showed heterogeneity. The
      estimated species number of 58 is equal to the actual number of species known
      from the country. The asymptotic shape of the accumulative species curve predicts
      that additional sampling efforts will not increase the number of species
      currently known from Hungary. These results suggest that the number of species in
      the country was estimated correctly and that the species accumulation curve
      levels off at an asymptotic value. Thus a considerable increase in species
      richness is not expected in the future. Even with the species composition
      changing the chance of species turn-over does exist. Overall, 36.7% of the
      European water bug species were found in Hungary. The differences in faunal
      composition between Hungary and its surrounding countries were caused by the rare
      or unique species, whereas 33 species are common in the faunas of the eight
      countries. Species richness does show a correlation with latitude, and similar
      species compositions were observed in the countries along the same latitude. The
      species list and the UTM-based database are now up-to-date for Hungary, and it
      will provide a basis for future studies of distributional and biodiversity
      patterns, biogeography, relative abundance and frequency of occurrences important
      in community ecology, or the determination of conservation status. 

PMID- 25987881
TI  - Systematics of the Rhinellamargaritifera complex (Anura, Bufonidae) from western
      Ecuador and Panama with insights in the biogeography of Rhinellaalata.
AB  - The Rhinellamargaritifera species group consists of 17 species of toads
      distributed in tropical and subtropical South America and eastern Central
      America. The identity of some of its species is poorly understood and there are
      numerous undescribed cryptic species. Among them, the status of
      Rhinellamargaritifera is one of the most problematic. Its range includes lowland
      rainforests separated by the Andes, the Chocoan rainforest to the west and the
      Amazonian rainforest to the east. This distribution is puzzling because the Andes
      are an old and formidable barrier to gene flow and therefore should generate
      vicariant speciation between disjunct lowland populations. Herein we clarify the
      taxonomy of populations of the Rhinellamargaritifera complex from Central America
      and the Choco region of South America. The morphological and genetic variation of
      Rhinellamargaritifera was examined from 39 populations from Choco, 24 from the
      upper Amazon region of Ecuador, and 37 from Panama, including the holotype of the
      Panamanian Rhinellaalata. Phylogenetic analyses were performed based on
      mitochondrial genes 12S rRNA, 16S rRNA, and cytochrome c oxidase I (COI) and the
      nuclear gene Tyrosinase (Tyr). The genetic and morphological data show that
      Panamanian and Chocoan populations are conspecific. In the phylogeny, populations
      from Choco and Panama form a well-supported clade. The morphology of the holotype
      of Rhinellaalata falls within the variation range of Panamanian and Chocoan
      populations. Based on all this evidence, we assign the populations from western
      Ecuador and Panama to Rhinellaalata and demonstrate that the unusual distribution
      pattern of "Rhinellamargaritifera" on both sides of the Andes was an artifact of
      incorrectly defined species boundaries. 

PMID- 25987882
TI  - Five new synonyms in Epimedium (Berberidaceae) from China.
AB  - Five new synonyms in Chinese Epimedium are designated in the present paper.
      Epimediumchlorandrum is treated as a synonym of Epimediumacuminatum;
      Epimediumrhizomatosum as a synonym of Epimediummembranaceum;
      Epimediumbrachyrrhizum as a synonym of Epimediumleptorrhizum; Epimediumdewuense
      as a synonym of Epimediumdolichostemon; and
      Epimediumsagittatumvar.oblongifoliolatum as a synonym of
      Epimediumborealiguizhouense. 

PMID- 25987883
TI  - Preliminary phylogenetic analysis of the Andean clade and the placement of new
      Colombian blueberries (Ericaceae, Vaccinieae).
AB  - The blueberry tribe Vaccinieae (Ericaceae) is particularly diverse in South
      America and underwent extensive radiation in Colombia where many endemics occur.
      Recent fieldwork in Colombia has resulted in valuable additions to the phylogeny
      and as well in the discovery of morphologically noteworthy new species that need
      to be phylogenetically placed before being named. This is particularly important,
      as the monophyly of many of the studied genera have not been confirmed. In order
      to advance our understanding of the relationships within neotropical Vaccinieae
      and advice the taxonomy of the new blueberry relatives, here we present the most
      comprehensive phylogenetic analysis for the Andean clade. Anthopterus,
      Demosthenesia, and Pellegrinia are among the putative Andean genera recovered as
      monophyletic, while other eight Andean genera were not. The analyses also showed
      that genera that have been traditionally widely defined are non-monophyletic and
      could be further split into more discrete groups. Four newly discovered Colombian
      Vaccinieae are placed in the monophyletic Satyria s.s. and the Psammisia I clade.
      Although these new species are endemic to the Colombian Western Cordillera and
      Choco biogeographic region and three are not known outside of Las Orquideas
      National Park, they do not form sister pairs. 

PMID- 25987884
TI  - New blueberry and mortino relatives (Ericaceae) from northwestern Colombia.
AB  - The inventory of the vascular plants of one of the richest and least studied
      floras, the Andean and Choco regions of northwestern Colombia, targets Las
      Orquideas National Park. As a result of field trips to areas never before
      collected, several epiphytic and small terrestrial shrubs in the family Ericaceae
      have been discovered in the Park's humid forests. Five new, morphologically
      remarkable species of Ericaceae (tribe Vaccinieae), are here described and
      illustrated. In a separate phylogenetic analysis, Psammisiapinnata Pedraza,
      Psammisiapseudoverticillata Pedraza, Satyriaorquidiensis Pedraza, and
      Satyriapterocalyx Pedraza, were placed by molecular sequence data within clades
      of the non-monophyletic genera Psammisia and Satyria; phylogenetic evidence for
      the placement of Psammisiasophiae Pedraza is still lacking. Their affinities are
      here discussed, along with their preliminary conservation status. 

PMID- 25987885
TI  - Studies of Malagasy Eugenia - IV: Seventeen new endemic species, a new
      combination, and three lectotypifications; with comments on distribution,
      ecological and evolutionary patterns.
AB  - Seventeen new endemic species of the genus Eugenia L. (Myrtaceae) are proposed
      from Madagascar, including: Eugeniaandapae N. Snow, Eugeniabarriei N. Snow,
      Eugeniabemangidiensis N. Snow, Eugeniacalciscopulorum N. Snow,
      Eugeniadelicatissima N. Snow, Callm. & Phillipson, Eugeniaechinulata N. Snow,
      Eugeniagandhii N. Snow, Eugeniahazonjia N. Snow, Eugeniaiantarensis N. Snow,
      Eugeniamalcomberi N. Snow, Eugeniamanomboensis N. Snow, Eugeniaobovatifolia N.
      Snow, Eugeniaranomafana N. Snow & D. Turk, Eugeniaravelonarivoi N. Snow & Callm.,
      Eugeniarazakamalalae N. Snow & Callm., Eugeniatiampoka N. Snow & Callm., and
      Eugeniawilsoniana N. Snow, and one new combination, Eugeniarichardii (Blume) N.
      Snow, Callm. & Phillipson is provided. Detailed descriptions, information on
      distribution and ecology, distribution maps, vernacular names (where known),
      digital images of types, comparisons to morphologically similar species.
      Preliminary assessment of IUCN risk of extinction and conservation
      recommendations are provided, including Vulnerable (4 species), Endangered (2
      species), and Critically Endangered (4 species). Lectotpyes are designated for
      Eugeniahovarum H. Perrier, Eugenianompa H. Perrier, and Eugeniascottii H. Perrier
      respectively. 

PMID- 25987886
TI  - Absorption mechanisms of Cu(2+) on a biogenic bixbyite-like Mn2O3 produced by
      Bacillus CUA isolated from soil.
AB  - BACKGROUND: Although most reported biogenic Mn oxides are hexagonal birnessites,
      other types of biogenic Mn oxides also commonly occur in the environment.
      However, sorption characteristics and underlying mechanisms of the adsorption of
      heavy-metal ions on these biogenic Mn oxides are still rarely addressed. In this
      study, the sorption mechanisms of Cu(II) on a low valence biogenic Mn oxide,
      poorly crystallized bixbyite-like Mn2O3 (alpha-Mn2O3), were investigated.
      RESULTS: The maximum adsorption capacity of Cu(II) onto this biogenic Mn oxide at
      pH 6.00 was 796 mmol/kg (0.45 mol Cu mol(-1) Mn). The complex structure of
      adsorbed Cu(II) was constrained using Cu extended X-ray absorption fine structure
      (EXAFS) analysis, combined with structural parameters of the biogenic Mn oxide
      with alternately arranged regular and distorted MnO6 octahedra obtained through
      multiple-FEFF fitting of Mn EXAFS data. The sorbed Cu(II) was found to coordinate
      with the biogenic Mn oxide particle edges as inner-sphere complexes. At a
      relatively low Cu(2+) loading (233 mmol/kg, pH 6.00), Cu(II) adsorbed onto the
      biogenic Mn oxide with two types of coordinated complexes, i.e., (1) coordinated
      with one regular/distorted MnO6 octahedron as a monodentate-mononuclear complex
      and (2) with two adjacent MnO6 octahedra as a bidentate-binuclear complex. While,
      at a relatively high Cu(2+) loading (787 mmol/kg, pH 6.00), only one type of
      coordinated complex was constrained, the adsorbed Cu(II) coordinated with one
      regular/distorted MnO6 octahedron as a monodentate-mononuclear complex.
      CONCLUSIONS: This research extends further insight into the bacterial Mn(II)
      oxidation in the environment and serves as a good reference for understanding the
      interactions between metal ions and biogenic low valence Mn oxides, which are
      still poorly explored either theoretically or practically.

PMID- 25987887
TI  - A novel multiplexed immunoassay identifies CEA, IL-8 and prolactin as prospective
      markers for Dukes' stages A-D colorectal cancers.
AB  - BACKGROUND: Current methods widely deployed for colorectal cancers (CRC)
      screening lack the necessary sensitivity and specificity required for population
      based early disease detection. Cancer-specific protein biomarkers are thought to
      be produced either by the tumor itself or other tissues in response to the
      presence of cancers or associated conditions. Equally, known examples of cancer
      protein biomarkers (e.g., PSA, CA125, CA19-9, CEA, AFP) are frequently found in
      plasma at very low concentration (pg/mL-ng/mL). New sensitive and specific assays
      are therefore urgently required to detect the disease at an early stage when
      prognosis is good following surgical resection. This study was designed to meet
      the longstanding unmet clinical need for earlier CRC detection by measuring
      plasma candidate biomarkers of cancer onset and progression in a clinical stage
      specific manner. EDTA plasma samples (1 MUL) obtained from 75 patients with
      Dukes' staged CRC or unaffected controls (age and sex matched with stringent
      inclusion/exclusion criteria) were assayed for expression of 92 human proteins
      employing the Proseek(r) Multiplex Oncology I proximity extension assay. An
      identical set of plasma samples were analyzed utilizing the Bio-Plex ProTM human
      cytokine 27-plex immunoassay. RESULTS: Similar quantitative expression patterns
      for 13 plasma antigens common to both platforms endorsed the potential efficacy
      of Proseek as an immune-based multiplex assay for proteomic biomarker research.
      Proseek found that expression of Carcinoembryonic Antigen (CEA), IL-8 and
      prolactin are significantly correlated with CRC stage. CONCLUSIONS: CEA, IL-8 and
      prolactin expression were found to identify between control (unaffected), non
      malignant (Dukes' A + B) and malignant (Dukes' C + D) stages.

PMID- 25987889
TI  - Identification of a self-regulatory pheromone system that controls nymph
      aggregation behavior of rice spittlebug Callitettix versicolor.
AB  - BACKGROUND: Nymphs of many spittlebug species are known to aggregate in one
      spittle mass, a behavior which greatly benefits the survival of the developing
      nymphs. Little is known, however, about the precise mechanisms that induce and
      regulate aggregation. Here, we investigated the aggregation behavior of nymphs of
      the rice spittlebug Callitettix versicolor, and analyzed the chemical composition
      of spittle masses. RESULTS: We identified six n-alkane compounds, namely un-, do
      , tri-, tetra-, penta- and hexadecane in the spittle mass. Importantly, we showed
      that solitary spittle mass (SSM) and aggregation spittle mass (ASM) differed
      significantly in the amounts and composition of these compounds. While un-, do-,
      tri-, tetra-and hexadecane were overrepresented in SSM, pentadecane was found at
      significantly higher levels in ASM. Electrophysiological experiments showed that
      antennae responses to these six compounds were significantly higher than to both
      the hexane and the docosane control, which suggests a specific role of the six
      volatile alkanes as pheromones. In agreement with this hypothesis, behavioral
      tests revealed that five of the six compounds (e.g. un-, do-, tri-, tetra-, and
      hexadecane) acted as attractants across a wide concentration range. Thus, these
      five compounds allow recruitment of additional nymphs to a growing spittle mass.
      The sixth compound, pentadecane, attracted nymphs at low doses, whereas at higher
      doses, this effect vanished, suggesting that this alkane functioned as a
      repellent, thus preventing recruitment of additional individuals to a full
      aggregation in a spittle mass. CONCLUSIONS: In summary, our study identified a
      simple, yet fully functional feedback mechanism which allows aggregation at low
      nymph numbers, while preventing over-crowding beyond a set number of nymphs
      within one spittle mass. In conclusion, our study provides new insights into C.
      versicolor development and behavior that should greatly facilitate the
      identification of new approaches for pheromonal control of this pest.

PMID- 25987888
TI  - Identification of sialylated glycoproteins from metabolically oligosaccharide
      engineered pancreatic cells.
AB  - In this study, we investigated the use of metabolic oligosaccharide engineering
      and bio-orthogonal ligation reactions combined with lectin microarray and mass
      spectrometry to analyze sialoglycoproteins in the SW1990 human pancreatic cancer
      line. Specifically, cells were treated with the azido N-acetylmannosamine analog,
      1,3,4-Bu3ManNAz, to label sialoglycoproteins with azide-modified sialic acids.
      The metabolically labeled sialoglyproteins were then biotinylated via the
      Staudinger ligation, and sialoglycopeptides containing azido-sialic acid glycans
      were immobilized to a solid support. The peptides linked to metabolically labeled
      sialylated glycans were then released from sialoglycopeptides and analyzed by
      mass spectrometry; in parallel, the glycans from azido-sialoglycoproteins were
      characterized by lectin microarrays. This method identified 75 unique N-glycosite
      containing peptides from 55 different metabolically labeled sialoglycoproteins of
      which 42 were previously linked to cancer in the literature. A comparison of two
      of these glycoproteins, LAMP1 and ORP150, in histological tumor samples showed
      overexpression of these proteins in the cancerous tissue demonstrating that our
      approach constitutes a viable strategy to identify and discover
      sialoglycoproteins associated with cancer, which can serve as biomarkers for
      cancer diagnosis or targets for therapy. 

PMID- 25987890
TI  - Quality of life and psychosocial well-being among children living with HIV at a
      care home in Southern India.
AB  - This study was designed to evaluate the quality of life (QOL) of children living
      with HIV at an institutional care home in Bangalore, India. The Sneha Care Home
      is a unique residence that provides educational and community support with a
      focus on physical, nutritional, medical, and psychological care for orphans and
      vulnerable children. Cross-sectional health measures and interview data were
      collected from 97 residents including 52 boys and 45 girls between 5 and 12 years
      of age (mean age = 9). QOL was measured with the Pediatric Quality of Life 4.0
      (PedsQL) Inventory. Caregivers perceived children to have an overall higher QOL
      than was self-reported by children (total score 83 vs. 78). Our findings
      indicated self-reported QOL decreased with age of the child, while caregiver
      reported QOL increased with age, suggesting a need to ensure greater
      psychological support for older children. Physical measures showed the children's
      clinical severity of disease remained well controlled living in this residential,
      values-based care home.

PMID- 25987891
TI  - A comparison of high-throughput techniques for assaying circadian rhythms in
      plants.
AB  - Over the last two decades, the development of high-throughput techniques has
      enabled us to probe the plant circadian clock, a key coordinator of vital
      biological processes, in ways previously impossible. With the circadian clock
      increasingly implicated in key fitness and signalling pathways, this has opened
      up new avenues for understanding plant development and signalling. Our tool-kit
      has been constantly improving through continual development and novel techniques
      that increase throughput, reduce costs and allow higher resolution on the
      cellular and subcellular levels. With circadian assays becoming more accessible
      and relevant than ever to researchers, in this paper we offer a review of the
      techniques currently available before considering the horizons in circadian
      investigation at ever higher throughputs and resolutions. 

PMID- 25987893
TI  - Global availability of data on HPV genotype-distribution in cervical, vulvar and
      vaginal disease and genotype-specific prevalence and incidence of HPV infection
      in females.
AB  - BACKGROUND: Country-level HPV genotyping data may be sought by decision-makers to
      gauge the genotype-specific burden of HPV-related diseases in their jurisdiction
      and assess the potential impact of HPV vaccines. We investigated, by country, the
      availability of published literature on HPV genotypes in cervical, vaginal and
      vulvar cancers and intraepithelial neoplasms (CINs, VaINs and VINs) and on
      prevalence and incidence of genital HPV infections among women without clinically
      manifest disease. FINDINGS: Primary sources of publications were the
      PubMed/Medline and EMBASE databases. Original studies or meta-analyses published
      from 2000, covering genotypes 16 and 18 and at least one of genotypes
      31/33/45/52/58, were included. Key exclusion criteria were language not English,
      cervical lesions not histologically confirmed (cytology only), special
      populations (e.g., immunocompromised) and, for cervical studies, small population
      (<50). A total of 727 studies reporting HPV genotype-specific data were
      identified: 366 for cervical cancers and CINs, 43 for vulvar or vaginal cancers
      and VINs/VaINs, and 395 and 21 for infection prevalence and incidence,
      respectively, in general female population samples. A large proportion of studies
      originated from a small set of countries. Cervical cancer/CIN typing data was
      scarce for several regions with the highest cervical cancer burden, including
      Eastern, Middle and Western Africa, Central America, South-East Asia, South Asia,
      and Eastern Europe. Data for vulvar/vaginal disease was limited outside of Europe
      and North America. CONCLUSIONS: Although a large body of published HPV genotype
      specific data is currently available, data gaps exist for genotype-specific
      infection incidence and several world regions with the highest cervical cancer
      burden.

PMID- 25987894
TI  - Mental health first aid training for the Bhutanese refugee community in the
      United States.
AB  - BACKGROUND: The aim of this study was to investigate the impact of Mental Health
      First Aid (MHFA) training for Bhutanese refugee community leaders in the U.S. We
      hypothesized that training refugee leaders would improve knowledge of mental
      health problems and treatment process and decrease negative attitudes towards
      people with mental illness. METHODS: One hundred and twenty community leaders
      participated in MHFA training, of whom 58 had sufficient English proficiency to
      complete pre- and post-tests. The questionnaires assessed each participant's
      ability to recognize signs of depression, knowledge about professional help and
      treatment, and attitudes towards people with mental illness. RESULTS: Between the
      pre- and post-test, participants showed significant improvement in the
      recognition of symptoms of depression and expressed beliefs about treatment that
      became more concordant with those of mental health professionals. However, there
      was no reduction in negative attitudes towards people with mental illness.
      CONCLUSIONS: MHFA training course is a promising program for Bhutanese refugee
      communities in the U.S. However, some adaptations may be necessary to ensure that
      MHFA training is optimized for this community.

PMID- 25987895
TI  - Role of human papillomaviruses in carcinogenesis.
AB  - The human papillomavirus (HPV) family comprises more than 170 different types
      that preferentially infect the mucosa of the genitals, upper-respiratory tract,
      or the skin. The 'high-risk HPV type', a sub-group of mucosal HPVs, is the cause
      of approximately 5% of all human cancers, which corresponds to one-third of all
      virus-induced tumours. Within the high-risk group, HPV16 is the most oncogenic
      type, being responsible for approximatively 50% of all worldwide cervical
      cancers. Many studies suggest that, in addition to the high-risk mucosal HPV
      types, certain cutaneous HPVs also have a role in the development of non-melanoma
      skin cancer (NMSC). Functional studies on the HPV early gene products showed that
      E6 and E7 play a key role in carcinogenesis. These two proteins use multiple
      mechanisms to evade host immune surveillance, allowing viral persistence, and to
      deregulate cell cycle and apoptosis control, thus facilitating the accumulation
      of DNA damage and ultimately cellular transformation. The demonstration that high
      risk HPV types are the etiological agents of cervical cancer allowed the
      implementation in the clinical routine of novel screening strategies for cervical
      lesions, as well as the development of a very efficient prophylactic vaccine.
      Because of these remarkable achievements, there is no doubt that in the coming
      decades we will witness a dramatic reduction of cervical cancer incidence
      worldwide. 

PMID- 25987896
TI  - Past and future of prophylactic ablation of the cervical squamocolumnar junction.
AB  - HPV vaccination has the potential to prevent the vast majority of cervical cancer
      cases but cervical cancer screening remains the only prevention strategy in adult
      unvaccinated women. The range of primary screening tests has expanded to include,
      in addition to cytology, visual inspection with acetic acid (VIA) and HPV
      testing. HPV-testing has the best sensitivity and negative predictive value, and
      a low-cost HPV test may make large-scale high-quality cervical cancer screening
      possible in low- and medium-income countries (LMICs). However, on account of its
      low specificity, HPV-testing would impose the additional burden of triaging HPV+
      women using cytology, colposcopy, VIA, or other not yet affordable tests. If
      minimally invasive treatments that have proven efficacious in HPV+ women with
      cervical intra-epithelial (CIN) grade 2 and 3 lesions also reduced future
      cervical cancer risk in lesion-free HPV+ women, the treatment of all HPV+ women
      would become attractive in LMICs in which screening should be performed as
      infrequently as possible. In the pre-mass screening era, gynaecologists widely
      practiced prophylactic ablation of the columnar epithelium visible on the
      ectocervix (ectopy) and squamocolumnar junction (SCJ) in the hope of preventing
      cervical cancer. Favourable outcomes were reported, especially from Finland, but
      conclusive results were not reached on account of weaknesses in the study
      methods. Indirect support for prophylactic ablation is provided by the hypothesis
      that some cells of embryonic origin derived from the SCJ are the source of high
      grade CIN and cervical carcinoma, and that they do not regenerate after SCJ
      ablation. SCJ cell elimination may avoid neoplastic transformation though not HPV
      reinfection. Randomised controlled trials are gold-standard, but if not feasible,
      an evaluation of the impact of prophylactic ablation could be done in the
      framework of large HPV-based screening programmes. Careful follow-up of lesion
      free HPV+ women would provide much needed information on the risk-to-benefit
      ratio of prophylactic ablation. 

PMID- 25987897
TI  - Performance of HPV DNA testing in the follow-up after treatment of high-grade
      cervical lesions, adenocarcinoma in situ (AIS) and microinvasive carcinoma.
AB  - BACKGROUND: Over the last two decades it has become clear that distinct types of
      human papillomavirus (HPV), the so-called high-risk types (hrHPV), are the major
      cause of cervical cancer. The hrHPV-DNA testing has shown excellent performance
      in several clinical applications from screening to the follow-up of
      conservatively treated patients. METHODS: We conducted a systematic review of the
      recent literature on the performance of HPV DNA testing in follow-up after
      treatment of high-grade cervical lesions, adenocarcinoma in situ, and
      microinvasive carcinoma compared to Pap smear cytology. RESULTS: Observational
      studies have demonstrated that the high risk hrHPV-DNA test is significantly more
      sensitive (95%) compared to follow-up cytology(70%) in detecting post-treatment
      squamous intraepithelial high-grade lesions. Moreover, in patients treated
      conservatively for cervical adenocarcinoma in situ, the hrHPV-DNA test is the
      most significant independent predictor of recurrent disease or progression to
      invasive cancer, and the combination of viral DNA testing and cytology reaches
      90% sensitivity in detecting persistent lesions at the first follow-up visit and
      100% at the second follow-up visit. The cause of microinvasive squamous cervical
      carcinoma is increasingly treated with conservative therapies in order to
      preserve fertility, and an effective strategy allowing early detection of
      residual or progressive disease has become more and more important in post
      treatment follow-up. Primary results seem to indicate that the median time for
      viral clearance is relatively longer compared with patients treated for CIN and
      suggest a prolonged surveillance for these patients. However, the potential
      clinical value of HPV-DNA testing in this clinical setting needs to be confirmed
      by further observations. CONCLUSIONS: The excellent sensitivity, negative
      predictive value, and optimal reproducibility of the hrHPV DNA testing, currently
      is considered a powerful tool in the clinicians' hands to better manage post
      treatment follow-up either in cervical squamous lesion or in situ adenocarcinoma.

PMID- 25987898
TI  - Human papillomavirus in anal squamous cell carcinoma: an angel rather than a
      devil?
AB  - Anal cancer is a rare disease with an increasing incidence worldwide but,
      unfortunately, even today the scientific community still has a limited knowledge
      and limited options of treatment. More than 50% of patients with anal cancer
      presenting at diagnosis with locoregional disease have good chances of cure with
      chemoradiotherapy (CT-RT). However, once patients develop metastatic spread, the
      prognosis is very poor. Human papillomavirus (HPV) is present in more than 80% of
      anal cancers and while multiple etiologic connections between HPV infection and
      anal cancer have already been well elucidated, its prognostic and/or predictive
      role is currently under investigation, especially among immunocompetent patients
      affected by this disease. In a single-institutional set, we have retrospectively
      analysed clinical data of 50 consecutive cases homogeneously treated with CT-RT
      for stage I-III anal squamous cell carcinoma. We found that HPV-positive anal
      cancers had a statistically significant improved five-year disease-free survival
      (DFS) compared to HPV-negative group. These findings could be explained by an
      increased chemo/radiosensitivity of HPV-positive tumours. Further efforts should
      be directed towards a better understanding of HPV-related oncogenesis and towards
      designing novel tailored strategies for the management of this disease both in
      terms of prevention and treatment. 

PMID- 25987899
TI  - Issues in optimising and standardising the accuracy and utility of the
      colposcopic examination in the HPV era.
AB  - For this tribute to Mario Sideri, we reviewed some of the current issues in
      colposcopy, many of which we were researching with him. The review concentrates
      on the impact of HPV testing on cervical screening, specifically on the practice
      of colposcopy as the major diagnostic procedure in cervical screening programmes.
      Topics include the changing population of women referred to colposcopy, evolving
      views of the colposcopic impression, differing approaches to directed and random
      biopsy, issues in teaching colposcopy using static images, and the development of
      colposcopy aids, and simplified visual assessment techniques. 

PMID- 25987900
TI  - VIN usual type-from the past to the future.
AB  - Usual vulvar intraepithelial neoplasia (uVIN) is the most common VIN type,
      generally related to a human papillomavirus (HPV) infection, predominantly type
      16. The incidence of uVIN has been increasing over the last decades, and a
      bimodal peak is observed at the age of 40-44 and over 55 years. Almost 40% of
      patients with uVIN have a past, concomitant or future HPV-associated lesion of
      the lower genital tract. HPV-related malignancies are associated with a
      persistent HPV infection. The host immune response is of crucial importance in
      determining clearance or persistence of both HPV infections and HPV-related VIN.
      About 60% of the patients present with symptoms. Clinical features of uVIN vary
      in site, number, size, shape, colour, and thickness of lesions. Multicentric
      disease is often present. Most uVIN lesions are positive at immunohistochemistry
      to p16(ink4a) and p14(arf), but negative to p53. Irrespective of surgical
      treatment used, uVIN recurrence rates are high. Positive margins do not predict
      the development of invasive disease and the need to re-excide the tissue around
      the scare remains to be demonstrated. Therefore, considering the low progression
      rate of uVIN and psycosexual sequelae, treatments should be as conservative as
      possible. Medical treatments available are mainly based on immunotherapy to
      induce normalisation of immune cell count in uVIN. None are approved by the food
      and drug administration (FDA) for the treatment of uVIN. If medical treatment is
      performed, adequate biopsies are required to reduce the risk of unrecognised
      invasive disease. Some studies suggest that failure to respond to immunotherapy
      might be related to a local immunosuppressive microenvironment, but knowledge of
      the uVIN microenvironment is limited. Moreover, our knowledge of the potential
      mechanisms involved in the escape of HPV-induced lesions from the immune system
      has many gaps. HPV vaccines have been demonstrated to be effective in preventing
      uVIN, with 94.9% efficacy in the HPV-naive population, while studies on
      therapeutic vaccines are limited. The low incidence of VIN requires large
      multicentre studies to determine the best way to manage affected patients and to
      investigate the immunological characteristics of the 'vulvar microenviroment'
      which leads to the persistence of HPV. 

PMID- 25987901
TI  - Screening of cervical cancer in Catalonia 2006-2012.
AB  - The early detection of intraepithelial lesions of the cervix, through the
      periodic examination of cervical cells, has been fundamental for the prevention
      of invasive cervical cancer and its related mortality. In this report, we
      summarise the cervical cancer screening activities carried out in Catalonia,
      Spain, within the National Health System during 2008-2011. The study population
      covers over two million women resident in the area. The evaluation includes
      758,690 cervical cytologies performed on a total of 595,868 women. The three-year
      coverage of cervical cytology among women aged between 25 and 65 years was 40.8%.
      About 50% of first screened women with negative results had not returned to the
      second screening round. The introduction of high-risk human papillomavirus DNA
      (HPV) detection, as a primary screening cotest with cytology among women over age
      40 with a poor screening history, significantly improved the detection of
      cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior
      to cytology alone. Cotesting did not improve the detection of CIN2+. The use of
      the HPV test for the triage of atypical squamous cell undetermined significance
      (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both
      cytology and HPV test) was largely performed by midwives (66.7%), followed by
      obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full
      use of online medical records. During the study period, educational activities
      for professionals and for women were carried out periodically. The organisation
      of screening as a population activity in which women are actively called to the
      screening visit and the introduction of HPV testing as a primary screening tool
      are strongly recommended to ensure the maximum population impact in the reduction
      of the cervical cancer burden. 

PMID- 25987902
TI  - Diagnostic work-up strategy for periprosthetic joint infections after total hip
      and knee arthroplasty: a 12-year experience on 320 consecutive cases.
AB  - BACKGROUND: Elective knee and hip arthroplasty is followed by infections in
      currently about 0.5-2.0 % of cases - a figure which is on the increase due to the
      rise in primary implants. Correct diagnosis early on is essential so that
      appropriate therapy can be administered. This work presents a retrospective
      analysis of the diagnoses of patients suffering infections after total hip or
      knee arthroplasty. METHODS: 320 patients with prosthetic joint infection (PJI)
      following knee or hip arthroplasty were identified. They comprised a) 172
      patients with an infection after total hip arthroplasty (THA): 56 % females (n =
      96) and 44 % males (n = 76) with a mean age of 70.9 (39-92) years; and 148
      patients with an infection after total knee arthroplasty (TKA): 55 % females (n =
      82) and 45 % males (n = 66) with a mean age of 70.7 (15-87) years. RESULTS:
      Although significantly more TKA than THA patients reported pain, erythema, a
      burning sensation and swelling, no differences between the two groups were
      observed with respect to dysfunction, fever or fatigue. However, significant
      differences were noted in the diagnosis of loosening (THA 55 %, TKA 31 %, p <
      0.001) and suspected infection using conventional X-rays (THA 61 %, TKA 29 %, p <
      0.001). FDG-PET-CT produced very good results in nearly 95 % of cases. There were
      no differences between THA and TKA patients regarding levels of inflammation
      markers. Histological evaluation proved to be significantly better than
      microbiological analysis. SUMMARY: The clinical picture may be non-specific and
      not show typical inflammatory symptoms for a long time, particularly in PJI of
      the hip. As imaging only provides reliable conclusions after the symptoms have
      persisted for a long time, morphological imaging is not suitable for the
      detection of early infections. FDG-PT-CT proved to be the most successful
      technique and is likely to be used more frequently in future. Nevertheless, there
      are currently no laboratory parameters which are suitable for the reliable
      primary diagnosis of PJI. Diagnosis requires arthrocentesis, and the fluid
      obtained should always be examined both microbiologically and histologically.

PMID- 25987903
TI  - Divergence of transcriptional landscape occurs early in B cell activation.
AB  - BACKGROUND: Signaling via B cell receptor (BCR) and Toll-like receptors (TLRs)
      results in activation of B cells with distinct physiological outcomes, but
      transcriptional regulatory mechanisms that drive activation and distinguish these
      pathways remain unknown. RESULTS: Two hours after ligand exposure RNA-seq, ChIP
      seq and computational methods reveal that BCR- or TLR-mediated activation of
      primary resting B cells proceeds via a large set of shared and a smaller subset
      of distinct signal-selective transcriptional responses. BCR stimulation resulted
      in increased global recruitment of RNA Pol II to promoters that appear to transit
      slowly to downstream regions. Conversely, lipopolysaccharide (LPS) stimulation
      involved an enhanced RNA Pol II transition from initiating to elongating mode
      accompanied by greater H3K4me3 activation markings compared to BCR stimulation.
      These rapidly diverging transcriptomic landscapes also show distinct repressing
      (H3K27me3) histone signatures, mutually exclusive transcription factor binding in
      promoters, and unique miRNA profiles. CONCLUSIONS: Upon examination of genome
      wide transcription and regulatory elements, we conclude that the B cell
      commitment to different activation states occurs much earlier than previously
      thought and involves a multi-faceted receptor-specific transcriptional landscape.

PMID- 25987904
TI  - Persistent organic pollutants as risk factors for type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is a major and fast growing public health
      problem. Although obesity is considered to be the main driver of the pandemic of
      T2DM, a possible contribution of some environmental contaminants, of which
      persistent organic pollutants (POPs) form a particular class, has been suggested.
      POPs are organic compounds that are resistant to environmental degradation
      through chemical, biological, and photolytic processes which enable them to
      persist in the environment, to be capable of long-range transport, bio accumulate
      in human and animal tissue, bio accumulate in food chains, and to have potential
      significant impacts on human health and the environment. Several epidemiological
      studies have reported an association between persistent organic pollutants and
      diabetes risk. These findings have been replicated in experimental studies both
      in human (in-vitro) and animals (in-vivo and in-vitro), and patho-physiological
      derangements through which these pollutants exercise their harmful effect on
      diabetes risk postulated. This review summarizes available studies, emphasises on
      limitations so as to enable subsequent studies to be centralized on possible
      pathways and bring out clearly the role of POPs on diabetes risk. 

PMID- 25987905
TI  - Independent external validation and comparison of prevalent diabetes risk
      prediction models in a mixed-ancestry population of South Africa.
AB  - BACKGROUND: Guidelines increasingly encourage the use of multivariable risk
      models to predict the presence of prevalent undiagnosed type 2 diabetes mellitus
      worldwide. However, no single model can perform well in all settings and
      available models must be tested before implementation in new populations. We
      assessed and compared the performance of five prevalent diabetes risk models in
      mixed-ancestry South Africans. METHODS: Data from the Cape Town Bellville-South
      cohort were used for this study. Models were identified via recent systematic
      reviews. Discrimination was assessed and compared using C-statistic and non
      parametric methods. Calibration was assessed via calibration plots, before and
      after recalibration through intercept adjustment. RESULTS: Seven hundred thirty
      seven participants (27 % male), mean age, 52.2 years, were included, among whom
      130 (17.6 %) had prevalent undiagnosed diabetes. The highest c-statistic for the
      five prediction models was recorded with the Kuwaiti model [C-statistic 0.68: 95
      % confidence: 0.63-0.73] and the lowest with the Rotterdam model [0. 64 (0.59
      0.69)]; with no significant statistical differences when the models were compared
      with each other (Cambridge, Omani and the simplified Finnish models). Calibration
      ranged from acceptable to good, however over- and underestimation was prevalent.
      The Rotterdam and the Finnish models showed significant improvement following
      intercept adjustment. CONCLUSIONS: The wide range of performances of different
      models in our sample highlights the challenges of selecting an appropriate model
      for prevalent diabetes risk prediction in different settings.

PMID- 25987906
TI  - Chemokine RANTES/CCL5 as an unknown link between wound healing in the jawbone and
      systemic disease: is prediction and tailored treatments in the horizon?
AB  - BACKGROUND: This research elucidates the question of whether common and
      widespread dental procedures (DP) like root filling (RF) and the removal of
      wisdom teeth (WT) contribute to chronic inflammation in the jawbone. Dentists, in
      carrying out these DP, can set off defective wound healing in the jawbone in
      ignorance of its connection to inflammatory mediators and the possibility of it
      being a hidden cause of chronic systemic diseases (SYD). MATERIALS AND METHODS:
      We examined samples of the jawbone for seven cytokines by multiplex analysis in
      three groups of jawbone areas. In order to clarify systemic interrelations,
      specimens from 16 patients were analyzed in areas of former surgery in the
      retromolar wisdom tooth area; specimens from 16 patients were analyzed in the
      jawbone, apically of teeth with RF; and specimens from 19 patients were of the
      healthy jawbone. Each of the retromolar and the apical jawbone samples showed
      clinically fatty degenerated and osteonecrotic medullary changes. RESULTS: All
      fatty necrotic and osteolytic jawbone (FDOJ) samples showed regulated on
      activation, normal T-cell expressed and secreted (RANTES) and fibroblast growth
      factor (FGF)-2 as the only extremely overexpressed cytokines. FDOJ cohorts showed
      a 30-fold mean overexpression of RANTES and a 20-fold overexpressed level of FGF
      2 when compared to healthy controls. CONCLUSIONS: As RANTES is discussed in the
      literature as a possible contributor to inflammatory diseases, and though it
      might have oncogenic effects, we hypothesize that FDOJ in areas of improper and
      incomplete wound healing in the jawbone might act as hyperactivated signaling
      pathways, while serving as an unknown source of "silent inflammation". Because of
      the wide range of RANTES in immune diseases, treating FDOJ can cover many
      potential prediction or prognosis of individual outcomes.

PMID- 25987907
TI  - Is serum lactate necessary in patients with normal anion gap and serum
      bicarbonate?
AB  - INTRODUCTION: There has been an increase in patients having serum lactate drawn
      in emergency situations. The objective of this study was to determine whether or
      not it was necessary to obtain a lactate level in patients with a normal serum
      bicarbonate level and anion gap. METHODS: This is a retrospective chart review
      evaluation of 304 patients who had serum lactate and electrolytes measured in an
      emergency setting in one academic medical center. RESULTS: In 66 patients who had
      elevated serum lactate (>2.2mmol/L), 45 (68%) patients had normal serum
      bicarbonate (SB) (greater than 21 mmol/L). Normal anion gap (AG) (normal range
      <16 mEq/l) was found in 51 of the 66 patients (77%). CONCLUSION: We found that
      among patients with elevated serum lactate, 77% had a normal anion gap and 68%
      had normal serum bicarbonate. We conclude serum lactate should be drawn based on
      clinical suspicion of anaerobic tissue metabolism independent of serum
      bicarbonate or anion gap values.

PMID- 25987908
TI  - Case series of patients with ruptured abdominal aortic aneurysm.
AB  - INTRODUCTION: Traditionally, patients with suspected ruptured abdominal aortic
      aneurysm (rAAA) are taken immediately for operative repair. Computed tomography
      (CT) has been considered contraindicated. However, with the emergence of
      endovascular repair, this approach to suspected rAAA could be changing. METHODS:
      We present retrospective data in a case series of 110 patients with rAAA.
      Patients were managed at a single tertiary medical center over a five-year
      period. At this site, there was an established multidisciplinary protocol in
      which patients with suspected rAAA undergo CT with consideration for endovascular
      aortic repair (EVAR). RESULTS: Our results demonstrated a mortality of 30% with
      our institutional protocol for CT in suspected rAAA. Comparing patients who
      ultimately had EVAR with open repair, those able to have endovascular aneurysm
      repair (EVAR) had lower mortality, shorter hospital stays for survivors, and a
      greater likelihood of being discharged to home than those with open repair. While
      survivors were more likely to have had EVAR, surviving patients were younger, had
      a significantly lower creatinine at presentation, and required fewer blood
      transfusions than those who died. CONCLUSION: Based on this case series, an
      institutional approach endorsing CT for presumed rAAA appears to be reasonable.
      Our results suggest that EVAR may be beneficial in appropriately-selected
      patients and that CT may potentially facilitate superior management options for
      patient care.

PMID- 25987909
TI  - Racial differences in opiate administration for pain relief at an academic
      emergency department.
AB  - INTRODUCTION: The decision to treat pain in the emergency department (ED) is a
      complex, idiosyncratic process. Prior studies have shown that EDs undertreat
      pain. Several studies demonstrate an association between analgesia administration
      and race. This is the first Midwest single institution study to address the
      question of race and analgesia, in addition to examining the effects of both
      patient and physician characteristics on race-based disparities in analgesia
      administration. METHODS: This was a retrospective chart review of patients
      presenting to an urban academic ED with an isolated diagnosis of back pain,
      migraine, or long bone fracture (LBF) from January 1, 2007 to December 31, 2011.
      Demographic and medication administration information was collected from patient
      charts by trained data collectors blinded to the hypothesis of the study. The
      primary outcome was the proportion of African-Americans who received analgesia
      and opiates, as compared to Caucasians, using Pearson's chi-squared test. We
      developed a multiple logistic regression model to identify which physician and
      patient characteristics correlated with increased opiate administration. RESULTS:
      Of the 2,461 patients meeting inclusion criteria, 57% were African-American and
      30% Caucasian (n=2136). There was no statistically significant racial difference
      in the administration of any analgesia (back pain: 86% vs. 86%, p=0.81; migraine:
      83% vs. 73%, p=0.09; LBF: 94% vs. 90%, p=0.17), or in opiate administration for
      migraine or LBF. African-Americans who presented with back pain were less likely
      to receive an opiate than Caucasians (50% vs. 72%, p<0.001). Secondary outcomes
      showed that higher acuity, older age, physician training in emergency medicine,
      and male physicians were positively associated with opiate administration.
      Neither race nor gender patient-physician congruency correlated with opiate
      administration. CONCLUSION: No race-based disparity in overall analgesia
      administration was noted for all three conditions: LBF, migraine, and back pain
      at this institution. A race-based disparity in the likelihood of receiving opiate
      analgesia for back pain was observed in this ED. The etiology of this is likely
      multifactorial, but understanding physician and patient characteristics of
      institutions may help to decrease the disparity by raising awareness of practice
      patterns and can provide the basis for quality improvement projects.

PMID- 25987910
TI  - Opioid education and nasal naloxone rescue kits in the emergency department.
AB  - INTRODUCTION: Emergency departments (EDs) may be high-yield venues to address
      opioid deaths with education on both overdose prevention and appropriate actions
      in a witnessed overdose. In addition, the ED has the potential to equip patients
      with nasal naloxone kits as part of this effort. We evaluated the feasibility of
      an ED-based overdose prevention program and described the overdose risk
      knowledge, opioid use, overdoses, and overdose responses among participants who
      received overdose education and naloxone rescue kits (OEN) and participants who
      received overdose education only (OE). METHODS: Program participants were
      surveyed by telephone after their ED visit about their substance use, overdose
      risk knowledge, history of witnessed and personal overdoses, and actions in a
      witnessed overdose including use of naloxone. RESULTS: A total of 415 ED patients
      received OE or OEN between January 1, 2011 and February 28, 2012. Among those, 51
      (12%) completed the survey; 37 (73%) of those received a naloxone kit, and 14
      (27%) received OE only. Past 30-day opioid use was reported by 35% OEN and 36%
      OE, and an overdose was reported by 19% OEN and 29% OE. Among 53% (27/51) of
      participants who witnessed another individual experiencing an overdose, 95% OEN
      and 88% OE stayed with victim, 74% OEN and 38% OE called 911, 26% OEN and 25% OE
      performed rescue breathing, and 32% OEN (n=6) used a naloxone kit to reverse the
      overdose. We did not detect statistically significant differences between OEN and
      OE-only groups in opioid use, overdose or response to a witnessed overdose.
      CONCLUSION: This is the first study to demonstrate the feasibility of ED-based
      opioid overdose prevention education and naloxone distribution to trained
      laypersons, patients and their social network. The program reached a high-risk
      population that commonly witnessed overdoses and that called for help and used
      naloxone, when available, to rescue people. While the study was retrospective
      with a low response rate, it provides preliminary data for larger, prospective
      studies of ED-based overdose prevention programs.

PMID- 25987911
TI  - Epinephrine for anaphylaxis: underutilized and unavailable.

PMID- 25987912
TI  - Reassessing After-Hour Arrival Patterns and Outcomes in ST-Elevation Myocardial
      Infarction.
AB  - INTRODUCTION: Differences in after-hours capability or performance of ST
      elevation myocardial infarction (STEMI) centers has the potential to impact
      outcomes of patients presenting outside of regular hours. METHODS: Using a
      prospective observational study, we analyzed all 1,247 non-transfer STEMI
      patients treated in 15 percutaneous coronary intervention (PCI) facilities in
      Dallas, Texas, during a 24-month period (2010-2012). Controlling for confounding
      factors through a variety of statistical techniques, we explored differences in
      door-to-balloon (D2B) and in-hospital mortality for those presenting on weekends
      vs. weekdays and business vs. after hours. RESULTS: Patients who arrived at the
      hospital on weekends had larger D2B times compared to weekdays (75 vs. 65
      minutes; KW=48.9; p<0.001). Patients who arrived after-hours had median D2B times
      >16 minutes longer than those who arrived during business hours and a higher
      likelihood of mortality (OR 2.23, CI [1.15-4.32], p<0.05). CONCLUSION: Weekends
      and after-hour PCI coverage is still associated with adverse D2B outcomes and in
      hospital mortality, even in major urban settings. Disparities remain in after
      hour STEMI treatment.

PMID- 25987913
TI  - Variability in the initial costs of care and one-year outcomes of observation
      services.
AB  - INTRODUCTION: The use of observation units (OUs) following emergency departments
      (ED) visits as a model of care has increased exponentially in the last decade.
      About one-third of U.S. hospitals now have OUs within their facilities. While
      their use is associated with lower costs and comparable level of care compared to
      inpatient units, there is a wide variation in OUs characteristics and operational
      procedures. The objective of this research was to explore the variability in the
      initial costs of care of placing patients with non-specific chest pain in
      observation units (OUs) and the one-year outcomes. METHODS: The author
      retrospectively investigated medical insurance claims of 22,962 privately insured
      patients (2009-2011) admitted to 41 OUs. Outcomes included the one-year chest
      pain/cardiovascular related costs and primary and secondary outcomes. Primary
      outcomes included myocardial infarction, congestive heart failure, stroke or
      cardiac arrest, while secondary outcomes included revascularization procedures,
      ED revisits for angina pectoris or chest pain and hospitalization due to
      cardiovascular diseases. The author aggregated the adjusted costs and prevalence
      rates of outcomes for patients over OUs, and computed the weighted coefficients
      of variation (WCV) to compare variations across OUs. RESULTS: There was minimal
      variability in the initial costs of care (WCV=2.2%), while the author noticed
      greater variability in the outcomes. Greater variability were associated with the
      adjusted cardiovascular-related costs of medical services (WCV=17.6%) followed by
      the adjusted prevalence odds ratio of patients experiencing primary outcomes
      (WCV=16.3%) and secondary outcomes (WCV=10%). CONCLUSION: Higher variability in
      the outcomes suggests the need for more standardization of the observation
      services for chest pain patients.

PMID- 25987914
TI  - Physician documentation of sepsis syndrome is associated with more aggressive
      treatment.
AB  - INTRODUCTION: Timely recognition and treatment of sepsis improves survival. The
      objective is to examine the association between recognition of sepsis and
      timeliness of treatments. METHODS: We identified a retrospective cohort of
      emergency department (ED) patients with positive blood cultures from May 2007 to
      January 2009, and reviewed vital signs, imaging, laboratory data, and
      physician/nursing charts. Patients who met systemic inflammatory response
      syndrome (SIRS) criteria and had evidence of infection available to the treating
      clinician at the time of the encounter were classified as having sepsis. Patients
      were dichotomized as RECOGNIZED if sepsis was explicitly articulated in the
      patient record or if a sepsis order set was launched, or as UNRECOGNIZED if
      neither of these two criteria were met. We used median regression to compare time
      to antibiotic administration and total volume of fluid resuscitation between
      groups, controlling for age, sex, and sepsis severity. RESULTS: SIRS criteria
      were present in 228/315 (72.4%) cases. Our record review identified sepsis
      syndromes in 214 (67.9%) cases of which 118 (55.1%) had sepsis, 64 (29.9%) had
      severe sepsis, and 32 (15.0%) had septic shock. The treating team contemplated
      sepsis (RECOGNIZED) in 123 (57.6%) patients. Compared to the UNRECOGNIZED group,
      the RECOGNIZED group had a higher use of antibiotics in the ED (91.9 vs.75.8%,
      p=0.002), more patients aged 60 years or older (56.9 vs. 33.0%, p=0.001), and
      more severe cases (septic shock: 18.7 vs. 9.9%, severe sepsis: 39.0 vs.17.6%,
      sepsis: 42.3 vs.72.5%; p<0.001). The median time to antibiotic (minutes) was
      lower in the RECOGNIZED (142) versus UNRECOGNIZED (229) group, with an adjusted
      median difference of -74 minutes (95% CI [-128 to -19]). The median total volume
      of fluid resuscitation (mL) was higher in the RECOGNIZED (1,600 mL) compared to
      the UNRECOGNIZED (1,000 mL) group. However, the adjusted median difference was
      not statistically significant: 262 mL (95% CI [ -171 to 694 mL]). CONCLUSION:
      Patients whose emergency physicians articulated sepsis syndrome in their
      documentation or who launched the sepsis order set received antibiotics sooner
      and received more total volume of fluid. Age <60 and absence of fever are factors
      associated with lack of recognition of sepsis cases.

PMID- 25987915
TI  - Association of insurance status with health outcomes following traumatic injury:
      statewide multicenter analysis.
AB  - INTRODUCTION: Recognizing disparities in definitive care for traumatic injuries
      created by insurance status may help reduce the higher risk of trauma-related
      mortality in this population. Our objective was to understand the relationship
      between patients' insurance status and trauma outcomes. METHODS: We collected
      data on all patients involved in traumatic injury from eight Level I and 15 Level
      IV trauma centers, and four non-designated hospitals through Arizona State Trauma
      Registry between January 1, 2008 and December 31, 2011. Of 109,497 records
      queried, we excluded 29,062 (26.5%) due to missing data on primary payer, sex,
      race, zip code of residence, injury severity score (ISS), and alcohol or drug
      use. Of the 80,435 cases analyzed, 13.3% were self-pay, 38.8% were Medicaid, 13%
      were Medicare, and 35% were private insurance. We evaluated the association
      between survival and insurance status (private insurance, Medicare, Medicaid, and
      self-pay) using multiple logistic regression analyses after adjusting for
      race/ethnicity (White, Black/African American, Hispanic, and American
      Indian/Alaska Native), age, gender, income, ISS and injury type (penetrating or
      blunt). RESULTS: The self-pay group was more likely to suffer from penetrating
      trauma (18.2%) than the privately insured group (6.0%), p<0.0001. There were more
      non-White (53%) self-pay patients compared to the private insurance group
      (28.3%), p<0.0001. Additionally, the self-pay group had significantly higher
      mortality (4.3%) as compared to private insurance (1.9%), p<0.0001. A simple
      logistic regression revealed higher mortality for self-pay patients (crude OR=
      2.32, 95% CI [2.07-2.67]) as well as Medicare patients (crude OR= 2.35, 95% CI
      [2.54-3.24]) as compared to private insurance. After adjusting for confounding, a
      multiple logistic regression revealed that mortality was highest for self-pay
      patients as compared to private insurance (adjusted OR= 2.76, 95% CI [2.30
      3.32]). CONCLUSION: These results demonstrate that after controlling for
      confounding variables, self-pay patients had a significantly higher risk of
      mortality following a traumatic injury as compared to any other insurance-type
      groups. Further research is warranted to understand this finding and possibly
      decrease the mortality rate in this population.

PMID- 25987916
TI  - Psychiatric and medical management of marijuana intoxication in the emergency
      department.
AB  - We use a case report to describe the acute psychiatric and medical management of
      marijuana intoxication in the emergency setting. A 34-year-old woman presented
      with erratic, disruptive behavior and psychotic symptoms after recreational
      ingestion of edible cannabis. She was also found to have mild hypokalemia and QT
      interval prolongation. Psychiatric management of cannabis psychosis involves
      symptomatic treatment and maintenance of safety during detoxification. Acute
      medical complications of marijuana use are primarily cardiovascular and
      respiratory in nature; electrolyte and electrocardiogram monitoring is indicated.
      This patient's psychosis, hypokalemia and prolonged QTc interval resolved over
      two days with supportive treatment and minimal intervention in the emergency
      department. Patients with cannabis psychosis are at risk for further psychotic
      sequelae. Emergency providers may reduce this risk through appropriate diagnosis,
      acute treatment, and referral for outpatient care. 

PMID- 25987917
TI  - Pediatric urinary retention and constipation: vaginal agenesis with
      hematometrocolpos.

PMID- 25987918
TI  - Rectus sheath hematoma: an unfortunate consequence of novel anticoagulants.

PMID- 25987919
TI  - Unusual placement of a central venous catheter: left pericardiophrenic vein.

PMID- 25987920
TI  - Vaginal bulge.

PMID- 25987921
TI  - Rare radiological pattern of diffuse esophageal spasm.

PMID- 25987922
TI  - Horner's Syndrome after Superficial Cervical Plexus Block.
AB  - Ultrasound-guided nerve blocks are becoming more essential for the management of
      acute pain in the emergency department (ED). With increased block frequency comes
      unexpected complications that require prompt recognition and treatment. The
      superficial cervical plexus block (SCPB) has been recently described as a method
      for ED management of clavicle fracture pain. Horner's syndrome (HS) is a rare and
      self-limiting complication of regional anesthesia in neck region such as brachial
      and cervical plexus blocks. Herein we describe the first reported case of a HS
      after an ultrasound-guided SCPB performed in the ED and discuss the complex
      anatomy of the neck that contributes to the occurrence of this complication. 

PMID- 25987923
TI  - Emergent presentation of decompensated mitral valve prolapse and atrial septal
      defect.
AB  - Mitral valve prolapse is not commonly on the list of differential diagnosis when
      a patient presents in the emergency department (ED) in severe distress,
      presenting with non-specific features such as abdominal pain, tachycardia and
      dyspnea. A healthy 55-year-old man without significant past medical history
      arrived in the ED with a unique presentation of a primary mitral valve prolapse
      with an atrial septal defect uncommon in cardiology literature. Early recognition
      of mitral valve prolapse in high-risk patients for severe mitral regurgitation or
      patients with underlying cardiovascular abnormalities such as an atrial septal
      defect is crucial to prevent morbid outcomes such as sudden cardiac death. 

PMID- 25987924
TI  - Anaphylaxis due to head injury.
AB  - Both anaphylaxis and head injury are often seen in the emergency department, but
      they are rarely seen in combination. We present a case of a 30-year-old woman who
      presented with anaphylaxis with urticaria and angioedema following a minor head
      injury. The patient responded well to intramuscular epinephrine without further
      complications or airway compromise. Prior case reports have reported angioedema
      from hereditary angioedema during dental procedures and maxillofacial surgery,
      but there have not been any cases of first-time angioedema or anaphylaxis due to
      head injury. 

PMID- 25987925
TI  - Morel-LAvallee lesion initially diagnosed as quadriceps contusion: ultrasound,
      MRI, and importance of early intervention.
AB  - Morel-Lavallee lesions (MLL) are rare, closed degloving injuries caused by trauma
      that delivers a shearing force to the soft tissue most commonly of the hip. If
      not treated in the acute and subacute setting these lesions are often complicated
      by re-accumulation of fluid, infection, or chronic pain. We present a unique case
      of a recurrent, massive medial knee/thigh MLL in which proper treatment was
      delayed due to initial diagnosis of a quadriceps contusion. We describe the
      ultrasound and magnetic resonance imaging findings of this patient and based on a
      review of recent literature propose that the initial management should have
      included early drainage/debridement, which likely could have prevented recurrence
      and significantly shortened the clinical course. 

PMID- 25987926
TI  - Rapid diagnosis of nonconvulsive status epilepticus using reduced-lead
      electroencephalography.
AB  - INTRODUCTION: Electroencephalography (EEG) is indicated for diagnosing
      nonconvulsive status epilepticus (NCSE) in a patient who has altered level of
      consciousness after a motor seizure. A study in a neonatal population found 94%
      sensitivity and 78% specificity for detection of seizure using a single-lead
      device. This study aims to show that a reduced montage EEG would detect 90% of
      seizures detected on standard EEG. METHODS: A portable Brainmaster EEG device was
      available in the emergency department (ED) at all times. Patients presenting to
      the ED with altered mental status and known history of seizure or a witnessed
      seizure having a standard EEG were eligible for this study. The emergency
      physician obtained informed consent from the legally authorized representative
      (LAR), while an ED technician attached the electrodes to the patient, and a
      research associate attached the electrodes to the wiring routing to the portable
      EEG module. A board-certified epileptologist interpreted the tracings via the
      Internet. Simultaneously, the emergency physician ordered a standard 23-lead EEG,
      which would be interpreted by the neurologist on call to read EEGs. We compared
      the epileptologist's interpretation of the reduced montage EEG to the results of
      the 23-lead EEG, which was considered the gold standard for detecting seizures.
      RESULTS: Twelve of 12 patients or 100% had the same findings on reduced-montage
      EEG as standard EEG. One of 12 patients or 8% had nonconvulsive seizure activity.
      CONCLUSION: The results are consistent with prior studies which have shown that 8
      48% of patients who have had a motor seizure continue to have nonconvulsive
      seizure activity on EEG. This study suggests that a bedside reduced-montage EEG
      can be used to make the diagnosis of NCSE in the ED. Further study will be
      conducted to see if this technology can be applied to the inpatient neurological
      intensive care unit setting.

PMID- 25987927
TI  - Bleb point: mimicker of pneumothorax in bullous lung disease.
AB  - In patients presenting with severe dyspnea, several diagnostic challenges arise
      in distinguishing the diagnosis of pneumothorax versus several other pulmonary
      etiologies like bullous lung disease, pneumonia, interstitial lung disease, and
      acute respiratory distress syndrome. Distinguishing between large pulmonary
      bullae and pneumothorax is of the utmost importance, as the acute management is
      very different. While multiple imaging modalities are available, plain
      radiographs may be inadequate to make the diagnosis and other advanced imaging
      may be difficult to obtain. Ultrasound has a very high specificity for
      pneumothorax. We present a case where a large pulmonary bleb mimics the lung
      point and therefore inaccurately suggests pneumothorax. 

PMID- 25987928
TI  - Diagnosis of a Strangulated Laparoscopic Incisional Hernia with Point-of-Care
      Ultrasonography.
AB  - The use of point-of-care ultrasound for the diagnosis of bowel obstructions and
      hernias is becoming increasingly common in the emergency department (ED). Using a
      relatively rare case of an incisional port hernia, we demonstrate the ultrasound
      findings of a strangulated hernia causing a partial small bowel obstruction. A 46
      year-old female presented four days following a laparoscopic surgery complaining
      of abdominal pain, nausea and lack of bowel movements. There was a palpable mass
      in the left lower quadrant under the 12mm trocar port incision. ED point-of-care
      ultrasound revealed herniated akinetic loops of bowel through her laparoscopy
      incision. This is the first case report to describe the use of point-of-care
      ultrasound for the diagnosis of a strangulated incisional port hernia at the
      bedside. 

PMID- 25987929
TI  - Rapid Extrication versus the Kendrick Extrication Device (KED): Comparison of
      Techniques Used After Motor Vehicle Collisions.
AB  - INTRODUCTION: The goal of this study was to compare application of the Kendrick
      Extrication Device (KED) versus rapid extrication (RE) by emergency medical
      service personnel. Our primary endpoints were movement of head, time to
      extrication and patient comfort by a visual analogue scale. METHODS: We used 23
      subjects in two scenarios for this study. The emergency medical services (EMS)
      providers were composed of one basic emergency medical technician (EMT), one
      advanced EMT. Each subject underwent two scenarios, one using RE and the other
      using extrication involving a commercial KED. RESULTS: Time was significantly
      shorter using rapid extraction for all patients. Angles of head turning were all
      significantly larger when using RE. Weight marginally modified the effect of KED
      versus RE on the "angle to right after patient moved to backboard (p= 0.029) and
      on subjective movement on patient questionnaire (p=0.011). No statistical
      differences were noted on patient discomfort or pain. CONCLUSION: This is a small
      experiment that showed decreased patient neck movement using a KED versus RE but
      resulted in increased patient movement in obese patients. Further studies are
      needed to determine if the KED improves any meaningful patient outcomes in the
      era of increased evidence-based medicine in emergency medical services.

PMID- 25987930
TI  - Self-reported provider safety in an urban emergency medical system.
AB  - INTRODUCTION: Emergency Medical Service (EMS) personnel often respond to
      dangerous scenes and encounter hostile individuals without police support. No
      recent data describes the frequency of physical or verbal assaults or which
      providers have increased fear for their safety. This information may help to
      guide interventions to improve safety. Our objective was to describe self
      reported abuse and perceptions of safety and to determine if there are
      differences between gender, shift, and years of experience in a busy two-tiered,
      third service urban EMS system. METHODS: This was a secondary analysis of an
      anonymous, cross-sectional work safety survey of EMS providers. This survey
      included demographics, years of experience, history of verbal and physical
      assault, safety behavior following an assault and perceptions of safety.
      Descriptive statistics were generated. RESULTS: Eighty-nine percent (196/221) of
      EMS providers completed the survey. Most were male (72%) and between the ages of
      25 and 50 years (66%). The majority of providers had worked in this service for
      more than five years (54%), and many for more than ten years (37%). Verbal
      assaults were reported by 88% (172/196, 95% CI [82.4%-91.6%]). Although 80%
      (156/196, 95% CI [73.4%-84.6%]) reported physical assaults, only 40% (62/156, 95%
      CI [32.4%-47.6%]) sought medical care and 49% (76/156, 95% CI [41%-56.6%])
      reported the assault to police. The proportion of those who sought medical care
      and reported the assault to the police was not the same across years of
      experience (p<0.0001). Fear for personal safety was reported by 68% (134/196, 95%
      CI [61.6%-74.5%]). There was no statistical difference in assault by gender;
      however, females feared more for their safety compared to men (38/50, 76% v
      96/142, 68%, p=0.02). The proportion of those who have ever been physically
      assaulted was not the same across shift worked (p=0.01). CONCLUSION: The majority
      of EMS providers surveyed reported an assault and certain groups had a higher
      rate of assault. Most assaults were not reported to the police and medical care
      was infrequently sought following an event. The majority of providers reported
      feeling fear for their personal safety. Further research into enhancing safety
      mechanisms is needed.

PMID- 25987931
TI  - Knowledge and Beliefs of EMS Providers toward Lights and Siren Transportation.
AB  - INTRODUCTION: The use of warning lights and siren (WLS) increases the risk of
      ambulance collisions. Multiple studies have failed to demonstrate a clinical
      benefit to the patients. We sought to investigate the degree to which providers
      understand the data and incorporate it into their practice. METHODS: The authors
      distributed an anonymous survey to prehospital providers under their medical
      direction at staff and quality assurance meetings. The surveys asked the
      providers' degree of agreement with four statements: transport with lights and
      siren shortens transport times; transport with lights and siren improves patient
      outcome; transport with lights and siren increases the risk of collision during
      transport; and transport with lights and siren reduces the utilization of "mutual
      aid" service. We compared responses between providers who had been in prior
      ambulance collisions and those who had not. RESULTS: Few responses reached
      statistical significance, but respondents tended towards agreement that WLS use
      shortens transport times, that it does not improve outcomes, and that it
      increases the risk of collision. Despite the overall agreement with the published
      literature, respondents report >80% of transports are conducted using WLS.
      CONCLUSION: The data demonstrate the surveyed providers are aware of the risk
      posed by WLS to themselves, their patients, and the public. Nevertheless, their
      practice in the absence of rigid protocols suggests they disregard this
      knowledge. Despite a large number of prior ambulance collisions among the
      surveyed group, a high number of transports are conducted using WLS.

PMID- 25987932
TI  - Using EMS Dispatch to Trigger STEMI Alerts Decreases Door-to-Balloon Times.
AB  - INTRODUCTION: We sought to determine the potential reduction in door-to-balloon
      time (DTB) by allowing paramedics to perform prehospital ST-Elevation Myocardial
      Infarction (STEMI) notification using brief communications via emergency medical
      services (EMS) 9-1-1 dispatchers as soon as they saw a STEMI on 12-lead
      electrocardiogram (EKG). Our hypothesis was that earlier cardiac catheterization
      lab (CCL) activation would improve overall DTB and avoid delays arising from on
      scene issues or the time required to deliver a full report. METHODS: The study
      setting was a single suburban community teaching hospital, which is a regional
      percutaneous coronary intervention (PCI) center with more than 120,000 Emergency
      Department (ED) visits/year and is serviced by a single tiered-response, advanced
      life support (ALS) paramedic-level agency. STEMI notifications from July 2009 to
      July 2012 occurred by either standard direct EMS-to-physician notification or by
      immediate 9-1-1 dispatch notification. In the 9-1-1 dispatcher-aided notification
      method, paramedics were asked to provide a brief one-sentence report using their
      lapel microphones upon immediate realization of a diagnostic EKG (usually within
      1-2 minutes of patient contact). This report to the 9-1-1 dispatcher included the
      patient's sex, age, and cardiologist (if known). The dispatcher then called the
      emergency department attending and informed them that a STEMI was being
      transported and that CCL activation was needed. We used retrospective chart
      review of a consecutive sample of patients from an existing STEMI registry to
      determine whether there was a statistically significant difference in DTB between
      the groups. RESULTS: Eight hundred fifty-six total STEMI alert patients arrived
      by EMS during the study. We excluded 730 notifications due to events such as
      cardiac arrest, arrhythmia, death, resolution of EKG changes and/or symptoms,
      cardiologist decision not to perform PCI, arrival as a transfer after prior
      stabilization at a referring facility or arriving by an EMS agency other than New
      Castle County EMS (NCC*EMS). Sixty-four (64) sequential patients from each group
      comprised the study sample. The average DTB (SD) for the standard communication
      method was 57.6 minutes (17.9), while that for dispatcher-aided communication was
      46.1 minutes (12.8), (mean difference 57.6-46.1 minutes=11.5 minutes with a 95%
      CI [6.06,16.94]) p=0.0001. In the dispatcher-aided group, 92% of patients (59/64)
      met standards of <=60 minute DTB time. Only 64% (41/64) met this goal in the
      standard communication group (p=0.0001). CONCLUSION: Brief, early notification of
      STEMI by paramedics through 9-1-1 dispatchers achieves earlier CCL activation in
      a hospital system already using EMS-directed CCL activation. This practice
      significantly decreased DTB and yielded a higher percentage of patients meeting
      the DTB<=60 minutes quality metric.

PMID- 25987934
TI  - Comments on "low-cost alternative external rotation shoulder brace and review of
      treatment in acute shoulder dislocations".

PMID- 25987933
TI  - Understanding Why Patients Return to the Emergency Department after Mild
      Traumatic Brain Injury within 72 Hours.
AB  - INTRODUCTION: Although there are approximately 1.1 million case presentations of
      mild traumatic brain injury (mTBI) in the emergency department (ED) each year,
      little data is available to clinicians to identify patients who are at risk for
      poor outcomes, including 72-hour ED return after discharge. An understanding of
      patients at risk for ED return visits during the hyperacute phase following head
      injury would allow ED providers to develop clinical interventions that reduce its
      occurrence and improve outcomes. METHODS: This institutional review board
      approved consecutive cohort study collected injury and outcome variables on
      adults with the purpose of identifying positive predictors for 72-hour ED return
      visits in mTBI patients. RESULTS: Of 2,787 mTBI patients, 145 (5%) returned
      unexpectedly to the ED within 72 hours of hospital discharge. Positive predictors
      for ED return visits included being male (p=0.0298), being black (p=0.0456),
      having a lower prehospital Glasgow Coma Score (p=0.0335), suffering the injury
      due to a motor vehicle collision (p=0.0065), or having a bleed on head computed
      tomography (CT) (p=0.0334). ED return visits were not significantly associated
      with age, fracture on head CT, or symptomology following head trauma. Patients
      with return visits most commonly reported post-concussion syndrome (43.1%), pain
      (18.7%), and recall for further clinical evaluation (14.6%) as the reason for
      return. Of the 124 patients who returned to the ED within 72 hours, one out of
      five were admitted to the hospital for further care, with five requiring
      intensive care unit stays and four undergoing neurosurgery. CONCLUSION:
      Approximately 5% of adult patients who present to the ED for mTBI will return
      within 72 hours of discharge for further care. Clinicians should identify at-risk
      individuals during their initial visits and attempt to provide anticipatory
      guidance when possible.

PMID- 25987935
TI  - Comments on "low-cost alternative external rotation shoulder brace and review of
      treatment in acute shoulder dislocations".

PMID- 25987936
TI  - Review of nipple reconstruction techniques and introduction of v to y technique
      in a bilateral wise pattern mastectomy or reduction mammaplasty.
AB  - INTRODUCTION: Nipple-areola complex reconstruction (NAR) is the final procedure
      in breast reconstruction after the majority of mastectomies. Many methods of NAR
      have been described, each with inherent advantages and disadvantages depending on
      local healthy tissue availability, previous scarring and procedures, and the
      operative morbidity of the NAR technique. Nipple reconstructions may be
      complicated by scars or previous nipple reconstruction, making the procedure more
      challenging. We propose the use of the V-Y advancement flap as a new method that
      is suitable for both novice and experienced surgeons wishing to broaden their
      range of techniques for difficult nipple reconstructions. METHODS: A traditional
      V-Y advancement flap is lifted at the site of the future nipple. Mastectomy scars
      from prior mastectomy, mammoplasty, or nipple reconstruction can be incorporated
      into the flap. The flap is folded caudally upon itself and the secondary defect
      at the apex of the flap is linearly closed. RESULTS: At 6-month postoperative
      evaluation, adequate nipple projection and patient satisfaction were achieved
      with this method. CONCLUSION: The V-Y advancement flap is a suitable method for
      achieving satisfactory results when faced with challenging NAR. The method is
      easy to perform, reproducible, has low operative morbidity, and incorporates
      previous wise pattern mastectomy or mammaplasty scars into the newly
      reconstructed nipple, thereby decreasing new scar formation on the breast and
      leading to favorable cosmetic results.

PMID- 25987937
TI  - Gene expression changes between patent and fused cranial sutures in a
      nonsyndromic craniosynostosis population.
AB  - OBJECTIVE: Craniosynostosis is a premature fusion of 1 or more cranial sutures.
      It may occur with additional morphological abnormalities (syndromic) or in
      isolation. Studies suggest that dysregulation of normal cell proliferation,
      differentiation, and migration has a role in isolated or nonsyndromic
      craniosynostosis but the molecular mechanisms remain unknown. The aim of this
      research is to identify genes differentially expressed in prematurely fused human
      suture compared to patent suture in nonsyndromic craniosynostosis. METHODS: Bone
      fragments from synostosed and patent sutures of 7 infants with nonsyndromic
      craniosynostosis were collected during surgical release of fused sutures. RNA was
      isolated from the fragments (7 patent and 7 fused) and global gene expression
      profiled using the Illumina WGE-DASL assay and HumanRef 8.0 Beadchip. RESULTS:
      Comparison of mRNA expression in fused and patent suture identified 68 genes
      significantly differentially expressed and having fold changes <= -2.0 and >= 2.0
      with a false discovery rate adjusted P value at .10 and 136 with adjusted P value
      of 0.15. SFRP2 (secreted frizzled-related protein 2) demonstrated the largest
      decrease in fused sutures. Analysis including only sagittal fused sutures
      revealed a set of 35 overlapping genes that may be involved in suture patency
      over all suture types. SPHKAP (sphingosine kinase type 1-interacting protein), a
      modulator of TGFbeta signaling, was significant in the sagittal subset.
      CONCLUSION: Differentially expressed genes were identified in fused suture
      relative to patent in a nonsyndromic craniosynostosis population. SFRP2 is likely
      important in suture patency. Genes having significant roles in osteoblastogenesis
      as negative regulators of canonical Wnt pathway were significantly downregulated.

PMID- 25987938
TI  - A biodegradable polyurethane dermal matrix in reconstruction of free flap donor
      sites: a pilot study.
AB  - We have developed a biodegradable temporizing matrix (BTM) capable of supporting
      secondary split-skin graft-take in animal studies. We report its first long-term
      implantation and use as a dermal scaffold in humans. This preliminary study
      assesses its ability to integrate, its ease of delamination, its ability to
      sustain split-skin graft in complex wounds, the degree of wound contraction, and
      ultimately the quality of the scar at 1 year postimplantation. Ten patients were
      recruited, each requiring elective free flap reconstruction. Free flap donor
      sites created were anterolateral thigh flaps, fibular osseocutaneous flaps, or
      radial/ulnar forearm (RF/UF) flaps. The BTM was implanted when the flap was
      detached from its donor site. Dressing changes were performed twice weekly. The
      time elapsed between implantation and delamination depended on the type of flap
      and thus the wound bed left. Once integrated, the BTMs were delaminated in
      theatre, and the surface of the "neodermis" was refreshed by dermabrasion, prior
      to application of a split-skin graft. The BTM integration occurred in all
      patients (100% in 6 patients, with 90%, 84%, 76%, and 60% integration in the
      remainder). Integrated BTM sustained successful graft-take in all patients.
      Complete take was marred in 2 patients, over areas of BTM that had not integrated
      and graft application was performed too early. The BTM can be applied into wounds
      in humans and can integrate, persist in the presence of infection, and sustain
      split-skin overgrafting, despite the trial group presenting with significant
      comorbidities. 

PMID- 25987939
TI  - Birth weight and incidence of surgical obstetric brachial plexus injury.
AB  - OBJECTIVES: (1) To analyze the birth weight of obstetric brachial plexus injury
      (OBPI) patients requiring one or more reconstructive surgeries and (2) to analyze
      whether there is any difference in the severity of the injury, and the outcome of
      the surgery between the macrosomic and nonmacrosomic OBPI patients. STUDY DESIGN:
      An observational cohort study was performed on 100 consecutive patients treated
      with surgery at the Texas Nerve and Paralysis Institute. Ninety of the 100
      patients underwent the modified Quad surgery, which improves the shoulder
      abduction and overall shoulder function. All OBPI patients in our study were
      assessed preoperatively and postoperatively by evaluating video recordings of
      active shoulder abduction. RESULTS: Using a 4000 g definition of macrosomia, 52%
      of patients would be considered macrosomic, and using a 4500 g definition of
      macrosomia, 18% of patients are considered macrosomic in our study. Permanent
      injury occurs also in average-birth-weight children. CONCLUSIONS: A significant
      percentage (48%-82% depending on definition of macrosomia) of OBPI patients
      requiring major reconstructive surgery had birth weights which would put them in
      the "normal" birth weight category. In addition, we found that there was no
      significant difference in the severity of the injury, and the outcome of the
      modified Quad surgical procedure between macrosomic and nonmacrosomic OBPI
      patients. However, there was a significant improvement in shoulder movement in
      both macrosomic and nonmacrosomic patients after modified Quad surgery.

PMID- 25987940
TI  - The Comparison of Intrathecal Morphine and IV Morphine PCA on Pain Control,
      Patient Satisfaction, Morphine Consumption, and Adverse Effects in Patients
      Undergoing Reduction Mammoplasty.
AB  - BACKGROUND: Following breast reduction procedures, the level of postoperative
      pain can be severe, and sufficient pain control influences a patient's
      physiological, immunological, and psychological status. OBJECTIVE: The aim of
      this study was to examine the use of intrathecal morphine (ITM) in breast
      reduction surgery with patient-controlled analgesia (PCA). METHODS: Sixty-two
      female patients who underwent breast reductions with the same technique
      participated in this study. The study group (ITM + PCA) included 32 patients; a
      single shot (0.2 mg) of ITM and intravenous morphine with PCA were administered.
      In the control group, morphine PCA alone was intravenously administered to 30
      patients. Comparisons between the groups of cumulative morphine consumption,
      visual analog scale scores, and patient satisfaction scores, which were the
      primary outcome measures, and adverse effects, which were the secondary outcome
      measures, were conducted. RESULTS: The patients in the 2 groups had similar
      degrees of pain and satisfaction scores. The study group had lower cumulative
      morphine consumption (P = .001) than the PCA-only control group; there was no
      statistically significant difference in adverse effects between the 2 groups.
      CONCLUSION: Intrathecal morphine may effectively control pain with lower total
      morphine consumption following breast reduction surgery.

PMID- 25987942
TI  - Mycobacterium Abscessus Abscess Post-thread Facial Rejuvenation Procedure.

PMID- 25987943
TI  - Ganglion cyst of the peroneus longus.

PMID- 25987941
TI  - Super-drained distally based neurofasciocutaneous sural flap: a case series and
      review of literature.
AB  - OBJECTIVE: The distally based neurofasciocutaneous sural flap is central to the
      armamentarium for the reconstruction of leg's distal third, ankle, and hindfoot.
      Despite the use of adapted techniques aimed at increasing the flap's reliability,
      venous congestion remains a frequently encountered problem. We present a venous
      super-drainage technique used by the senior author to reduce venous congestion
      and improve flap reliability when harvesting larger flaps. METHODS: A
      retrospective chart review, from January 2002 to October 2008, at 2 tertiary care
      centers, was conducted on all cases of inferior limb reconstruction with reverse
      sural flaps on defects greater than 10 * 5 cm. In addition, a literature review
      was carried out to examine the average sural flap surface area and reported
      complications published from 1992 to 2012. We then compared our results with
      those published in the literature. RESULTS: A total of 15 flaps were identified.
      Mean flap dimensions were 14 * 8.5 cm (mean area = 115.27 cm(2); 95% confidence
      interval, 99.28-131.26). None of the flaps developed complications (arterial or
      venous insufficiency, partial/complete necrosis). The average flap surface area
      in the literature is 55.08 cm(2), with a 22% rate of total complications. We
      harvested significantly larger flaps (P < .001) with a significantly lower total
      complication rate (P < .05) when compared with that reported in the literature.
      CONCLUSION: Anastomosing the proximal end of the lesser saphenous vein with a
      vein at the defect site improves venous outflow, effectively reducing the
      incidence of venous congestion, increases the potential flap size, and improves
      reliability.

PMID- 25987944
TI  - The leech condo: an innovative approach to containing leeches on a congested
      flap.

PMID- 25987945
TI  - Thromboangiitis Obliterans (Buerger's Disease).

PMID- 25987946
TI  - Tick bite with target lesion complicating routine cast immobilization.

PMID- 25987947
TI  - A growing lesion of the lip.

PMID- 25987948
TI  - Rhinophyma.

PMID- 25987949
TI  - The danger of posterior plagiocephaly.

PMID- 25987951
TI  - Type 2 diabetes among Asian Americans: Prevalence and prevention.
AB  - Type 2 diabetes mellitus (T2DM) is a growing problem among Asian Americans. Based
      on the Centers for Disease Control, the age-adjusted prevalence of T2DM for Asian
      Americans is 9%, placing them at "moderate risk". However differential patterns
      of disease burden emerge when examining disaggregated data across Asian American
      ethnic groups; with Filipino, Pacific Islander, Japanese, and South Asian groups
      consistently described as having the highest prevalence of T2DM. Disentangling
      and strengthening prevalence data is vital for on-going prevention efforts. The
      strongest evidence currently available to guide the prevention of T2DM in the
      United States comes from a large multicenter randomized clinical control trial
      called the Diabetes Prevention Program, which targets individual lifestyle
      behavior changes. It has been translated and adopted for some Asian American
      groups, and shows promise. However stronger study designs and attention to
      several key methodological considerations will improve the science. Increased
      attention has also been directed toward population level downstream prevention
      efforts. Building an infrastructure that includes both individual and population
      approaches is needed to prevent T2DM among Asian American populations, and is
      essential for reducing health disparities. 

PMID- 25987952
TI  - Adipose tissue fibrosis.
AB  - The increasing prevalence of obesity causes a major interest in white adipose
      tissue biology. Adipose tissue cells are surrounded by extracellular matrix
      proteins whose composition and remodeling is of crucial importance for cell
      function. The expansion of adipose tissue in obesity is linked to an
      inappropriate supply with oxygen and hypoxia development. Subsequent activation
      of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and
      initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and
      excess triglycerides are stored in ectopic tissues. Stressed adipocytes and
      hypoxia contribute to immune cell immigration and activation which further
      aggravates adipose tissue fibrosis. There is substantial evidence that adipose
      tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in
      the clinical setting. Peroxisome proliferator activated receptor gamma agonists
      and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin
      resistance. Current knowledge suggests that antifibrotic drugs, increasing
      adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue
      function and thereby ameliorate metabolic diseases. 

PMID- 25987950
TI  - Epigenetic reduction of DNA repair in progression to gastrointestinal cancer.
AB  - Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair
      genes cause increased risk of gastrointestinal (GI) cancer. In sporadic GI
      cancers, mutations in DNA repair genes are relatively rare. However, epigenetic
      alterations that reduce expression of DNA repair genes are frequent in sporadic
      GI cancers. These epigenetic reductions are also found in field defects that give
      rise to cancers. Reduced DNA repair likely allows excessive DNA damages to
      accumulate in somatic cells. Then either inaccurate translesion synthesis past
      the un-repaired DNA damages or error-prone DNA repair can cause mutations.
      Erroneous DNA repair can also cause epigenetic alterations (i.e., epimutations,
      transmitted through multiple replication cycles). Some of these mutations and
      epimutations may cause progression to cancer. Thus, deficient or absent DNA
      repair is likely an important underlying cause of cancer. Whole genome sequencing
      of GI cancers show that between thousands to hundreds of thousands of mutations
      occur in these cancers. Epimutations that reduce DNA repair gene expression and
      occur early in progression to GI cancers are a likely source of this high genomic
      instability. Cancer cells deficient in DNA repair are more vulnerable than normal
      cells to inactivation by DNA damaging agents. Thus, some of the most clinically
      effective chemotherapeutic agents in cancer treatment are DNA damaging agents,
      and their effectiveness often depends on deficient DNA repair in cancer cells.
      Recently, at least 18 DNA repair proteins, each active in one of six DNA repair
      pathways, were found to be subject to epigenetic reduction of expression in GI
      cancers. Different DNA repair pathways repair different types of DNA damage.
      Evaluation of which DNA repair pathway(s) are deficient in particular types of GI
      cancer and/or particular patients may prove useful in guiding choice of
      therapeutic agents in cancer therapy. 

PMID- 25987954
TI  - Adapting chronic care models for diabetes care delivery in low-and-middle-income
      countries: A review.
AB  - A contextual review of models for chronic care was done to develop a context
      adapted chronic care model-based service delivery model for chronic conditions
      including diabetes. The Philippines was used as the setting of a low-to-middle
      income country. A context-based narrative review of existing models for chronic
      care was conducted. A situational analysis was done at the grassroots level,
      involving the leaders and members of the community, the patients, the local
      health system and the healthcare providers. A second analysis making use of
      certain organizational theories was done to explore on improving feasibility and
      acceptability of organizing care for chronic conditions. The analyses indicated
      that care for chronic conditions may be introduced, considering the needs of
      people with diabetes in particular and the community in general as recipients of
      care, and the issues and factors that may affect the healthcare workers and the
      health system as providers of this care. The context-adapted chronic care model
      based service delivery model was constructed accordingly. Key features are:
      incorporation of chronic care in the health system's services; assimilation of
      chronic care delivery with the other responsibilities of the healthcare workers
      but with redistribution of certain tasks; and ensuring that the recipients of
      care experience the whole spectrum of basic chronic care that includes education
      and promotion in the general population, risk identification, screening,
      counseling including self-care development, and clinical management of the
      chronic condition and any co-morbidities, regardless of level of control of the
      condition. This way, low-to-middle income countries can introduce and improve
      care for chronic conditions without entailing much additional demand on their
      limited resources. 

PMID- 25987955
TI  - How the kidney hyperfiltrates in diabetes: From molecules to hemodynamics.
AB  - In this review, we focused on two molecules, connexin and sodium-glucose
      cotransporter, which can link to diabetic hyperfiltration. In diabetic kidney,
      the activation of renin-angiotensin system occurs simultaneously with glomerular
      hyperfiltration. The latter largely depends on pathophysiological afferent
      arteriolar dilation in the presence of high angiotensin II. As a mechanistic
      basis for the above, tubular hypothesis has been proposed for type 1 diabetic
      patients as well as experimental models. Although tubular hypothesis has not been
      well evaluated in type 2 diabetes, clinical observations support that tubular
      hypothesis is true also in type 2 diabetes. Recent results on tubular hypothesis
      along with connexin abnormality in type 2 diabetes were revisited. In addition,
      the importance of sodium-glucose cotransporter in diabetic hyperfiltration is
      discussed. The link between salt paradox and the activation of renin-angiotensin
      system will be also reviewed. 

PMID- 25987953
TI  - Toxic stress, inflammation and symptomatology of chronic complications in
      diabetes.
AB  - Diabetes affects at least 382 million people worldwide and the incidence is
      expected to reach 592 million by 2035. The incidence of diabetes in youth is
      skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5%
      increase in type 2 diabetes in the United States between 2001 and 2009. The
      effects of toxic stress, the culmination of biological and environmental
      interactions, on the development of diabetes complications is gaining attention.
      Stress impacts the hypothalamus-pituitary-adrenal axis and contributes to
      inflammation, a key biological contributor to the pathogenesis of diabetes and
      its associated complications. This review provides an overview of common diabetic
      complications such as neuropathy, cognitive decline, depression, nephropathy and
      cardiovascular disease. The review also provides a discussion of the role of
      inflammation and stress in the development and progression of chronic
      complications of diabetes, associated symptomatology and importance of early
      identification of symptoms of depression, fatigue, exercise intolerance and pain.

PMID- 25987958
TI  - Lean diabetes mellitus: An emerging entity in the era of obesity.
AB  - Much has been published on the characteristics of type 2 diabetes mellitus and
      its association with the epidemic of obesity. But relatively little is known
      about the incidence of lean diabetes, progression of disease and fate of the
      patients with low-normal body mass index (< 25). Studies in developing countries
      have shown that the clinical characteristics of these patients include history of
      childhood malnutrition, poor socioeconomic status, relatively early age of onset
      and absence of ketosis on withdrawal of insulin. In the United States, recent
      studies showed that the lean, normal weight diabetes is not rare especially among
      minority populations. They showed that these patients are mainly males, have
      higher prevalence of insulin use indicating rapid beta cell failure. They might
      have increased total, cardiovascular and non cardiovascular mortality when
      compared to obese diabetic patients. In this review, the epidemiologic and
      clinical features of lean diabetes are presented. The potential causal mechanisms
      of this emerging diabetes type that may include genetic, autoimmune, acquired and
      behavioral factors are discussed. The need for studies to further elucidate the
      causation as well as specific prevention and treatment of lean diabetes is
      emphasized. 

PMID- 25987959
TI  - Psychological themes that influence self-management of type 1 diabetes.
AB  - It has long been accepted that psychological factors adversely influence efforts
      to optimise glycaemic control. These are often unrecognised in terms of clinical
      assessment and therefore under reported. This essay presents an introduction to
      psychological issues that interact with psychiatric co-morbidities and diabetes
      specific distress, and a case scenario illustrating the interconnectedness of
      presenting problems and themes. In the way that we cannot separate carbohydrate
      counting, blood glucose monitoring and insulin dose adjustment in the
      understanding of a presenting problem such as poor control, so we cannot separate
      the concurrent thoughts, feelings, and behaviours. Each of these emotional
      aspects are self-managed either through avoidance, or by delayed disclosure and
      are frequently associated with poor health outcomes. There is a requirement for
      the healthcare team to be sensitised to these issues and to develop styles of
      communication that are empathic, reflective and non judgemental. A brief outline
      of evidence-based psychotherapy treatments is given. 

PMID- 25987956
TI  - Effects of exercise on brain functions in diabetic animal models.
AB  - Human life span has dramatically increased over several decades, and the quality
      of life has been considered to be equally important. However, diabetes mellitus
      (DM) characterized by problems related to insulin secretion and recognition has
      become a serious health problem in recent years that threatens human health by
      causing decline in brain functions and finally leading to neurodegenerative
      diseases. Exercise is recognized as an effective therapy for DM without
      medication administration. Exercise studies using experimental animals are a
      suitable option to overcome this drawback, and animal studies have improved
      continuously according to the needs of the experimenters. Since brain health is
      the most significant factor in human life, it is very important to assess brain
      functions according to the different exercise conditions using experimental
      animal models. Generally, there are two types of DM; insulin-dependent type 1 DM
      and an insulin-independent type 2 DM (T2DM); however, the author will mostly
      discuss brain functions in T2DM animal models in this review. Additionally, many
      physiopathologic alterations are caused in the brain by DM such as increased
      adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia,
      insulin and leptin resistance, and dysregulation of neurotransmitters and
      declined neurogenesis in the hippocampus and we describe how exercise corrects
      these alterations in animal models. The results of changes in the brain
      environment differ according to voluntary, involuntary running exercises and
      resistance exercise, and gender in the animal studies. These factors have been
      mentioned in this review, and this review will be a good reference for studying
      how exercise can be used with therapy for treating DM. 

PMID- 25987957
TI  - Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition.
AB  - Diabetes mellitus is increasing at an alarming rate and has become a global
      challenge. Insulin resistance in target tissues and a relative deficiency of
      insulin secretion from pancreatic beta-cells are the major features of type 2
      diabetes (T2D). Chronic low-grade inflammation in T2D has given an impetus to the
      field of immuno-metabolism linking inflammation to insulin resistance and beta
      cell dysfunction. Many factors advocate a causal link between metabolic stress
      and inflammation. Numerous cellular factors trigger inflammatory signalling
      cascades, and as a result T2D is at the moment considered an inflammatory
      disorder triggered by disordered metabolism. Cellular mechanisms like activation
      of Toll-like receptors, Endoplasmic Reticulum stress, and inflammasome activation
      are related to the nutrient excess linking pathogenesis and progression of T2D
      with inflammation. This paper aims to systematically review the metabolic profile
      and role of various inflammatory pathways in T2D by capturing relevant evidence
      from various sources. The perspectives include suggestions for the development of
      therapies involving the shift from metabolic stress to homeostasis that would
      favour insulin sensitivity and survival of pancreatic beta-cells in T2D. 

PMID- 25987960
TI  - Insulin action in muscle and adipose tissue in type 2 diabetes: The significance
      of blood flow.
AB  - Under normal metabolic conditions insulin stimulates microvascular perfusion
      (capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and
      thus increases blood flow mainly after meal ingestion or physical exercise. This
      helps the delivery of insulin itself but also that of substrates and of other
      signalling molecules to multiple tissues beds and facilitates glucose disposal
      and lipid kinetics. This effect is impaired in insulin resistance and type 2
      diabetes early in the development of metabolic dysregulation and reflects early
      onset endothelial dysfunction. Failure of insulin to increase muscle and adipose
      tissue blood flow results in decreased glucose handling. In fat depots, a blunted
      postprandial blood flow response will result in an insufficient suppression of
      lipolysis and an increased spill over of fatty acids in the circulation, leading
      to a more pronounced insulin resistant state in skeletal muscle. This defect in
      blood flow response is apparent even in the prediabetic state, implying that it
      is a facet of insulin resistance and exists long before overt hyperglycaemia
      develops. The following review intends to summarize the contribution of blood
      flow impairment to the development of the atherogenic dysglycemia and
      dyslipidaemia. 

PMID- 25987961
TI  - Assessment of cardiovascular risk in diabetes: Risk scores and provocative
      testing.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality
      among patients with diabetes mellitus, who have a risk of cardiovascular
      mortality two to four times that of people without diabetes. An individualised
      approach to cardiovascular risk estimation and management is needed. Over the
      past decades, many risk scores have been developed to predict CVD. However, few
      have been externally validated in a diabetic population and limited studies have
      examined the impact of applying a prediction model in clinical practice.
      Currently, guidelines are focused on testing for CVD in symptomatic patients.
      Atypical symptoms or silent ischemia are more common in the diabetic population,
      and with additional markers of vascular disease such as erectile dysfunction and
      autonomic neuropathy, these guidelines can be difficult to interpret. We propose
      an algorithm incorporating cardiovascular risk scores in combination with typical
      and atypical signs and symptoms to alert clinicians to consider further
      investigation with provocative testing. The modalities for investigation of CVD
      are discussed. 

PMID- 25987962
TI  - Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide
      polymorphisms of inflammatory cytokines.
AB  - Inflammation plays a significant role in the etiology of type 2 diabetes mellitus
      (T2DM). The rise in the pro-inflammatory cytokines is the essential step in
      glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and
      beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6,
      IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-alpha), C-reactive protein,
      resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins.
      Diabetes mellitus has firm genetic and very strong environmental influence;
      exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms
      (SNPs) in various genes including those of pro and anti-inflammatory cytokines
      have been reported as a risk for T2DM. Not all the SNPs have been confirmed by
      unifying results in different studies and wide variations have been reported in
      various ethnic groups. The inter-ethnic variations can be explained by the fact
      that gene expression may be regulated by gene-gene, gene-environment and gene
      nutrient interactions. This review highlights the impact of these interactions on
      determining the role of single nucleotide polymorphism of IL-6, TNF-alpha,
      resistin and adiponectin in pathogenesis of T2DM. 

PMID- 25987963
TI  - Attenuating type 2 diabetes with postpartum interventions following gestational
      diabetes mellitus.
AB  - Women with a history of gestational diabetes should be screened during and after
      the postpartum period because of a high risk for developing type 2 diabetes
      mellitus. Although differences exist between guidelines practiced throughout
      various parts of the world, all recommend the use of cutoffs for fasting and/or
      post-load plasma glucose to diagnose diabetes or pre-diabetes. The use of these
      glycemic parameters could be optimized when a trend is observed, rather than
      considering them as isolated values at various time points. As the presence of
      insulin resistance and beta-cell dysfunction start before glycemic changes are
      evident, the estimation of insulin sensitivity and beta-cell function by
      Homeostatic Model Assessment is suggested for women who have additional risk
      factors for diabetes, such as obesity. Disease-modifying lifestyle intervention
      should be the first-line strategy to prevent or delay the onset of diabetes in
      women with a history of gestational diabetes mellitus. Intensive lifestyle
      interventions are designed to decrease caloric intake and increase physical
      activity in order to reduce body weight and fat, which will in turn reduce
      insulin resistance. This article also reviews unique problems of postpartum
      women, which should be considered when designing and implementing an
      intervention. Innovative "out of the box" thinking is appreciated, as continued
      adherence to a program is a challenge to both the women and the health care
      personnel who deal with them. 

PMID- 25987965
TI  - Advanced glycation end-product expression is upregulated in the gastrointestinal
      tract of type 2 diabetic rats.
AB  - AIM: To investigate changes in advanced glycation end products (AGEs) and their
      receptor (RAGE) expression in the gastrointestinal (GI) tract in type 2 diabetic
      rats. METHODS: Eight inherited type 2 diabetic rats Goto-Kakizak (GK) and ten age
      matched normal rats were used in the study. From 18 wk of age, the body weight
      and blood glucose were measured every week and 2 wk respectively. When the rats
      reached 32 wk, two-centimeter segments of esophagus, duodenum, jejunum, ileum,
      and colon were excised and the wet weight was measured. The segments were fixed
      in 10% formalin, embedded in paraffin and five micron sections were cut. The
      layer thickness was measured in Hematoxylin and Eosin-stained slides. AGE [N
      epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were
      detected by immunohistochemistry staining and image analysis was done using
      Sigmascan Pro 4.0 image analysis software. RESULTS: The blood glucose
      concentration (mmol/L) at 18 wk age was highest in the GK group (8.88 +/- 1.87 vs
      6.90 +/- 0.43, P < 0.001), a difference that continued to exist until the end of
      the experiment. The wet weight per unit length (mg/cm) increased in esophagus,
      jejunum and colon from the normal to the GK group (60.64 +/- 9.96 vs 68.56 +/-
      11.69, P < 0.05 for esophagus; 87.01 +/- 9.35 vs 105.29 +/- 15.45, P < 0.01 for
      jejunum; 91.37 +/- 7.25 vs 97.28 +/- 10.90, P < 0.05 for colon). Histologically,
      the layer thickness of the GI tract was higher for esophagus, jejunum and colon
      in the GK group [full thickness (MUm): 575.37 +/- 69.22 vs 753.20 +/- 150.41, P <
      0.01 for esophagus; 813.51 +/- 44.44 vs 884.81 +/- 45.31, P < 0.05 for jejunum;
      467.12 +/- 65.92 vs 572.26 +/- 93.60, P < 0.05 for colon]. In esophagus, the AGE
      and RAGE mainly distributed in striated muscle cells and squamous epithelial
      cells. The AGE distribution was much stronger in the GK group compared to the
      normal group both in the striated muscle layer and mucosa layer (immuno-positive
      area/ total measuring area %: 4.52 +/- 0.89 vs 10.96 +/- 1.34, P < 0.01 for
      muscle; 8.90 +/- 2.62 vs 22.45 +/- 1.26, P < 0.01 for mucosa). No visible
      difference was found for RAGE distribution between the two groups. In the
      intestine AGE and RAGE distributed in epithelial cells of villi and crypt. RAGE
      was also found in neurons in the myenteric and submucosal plexus. The intensity
      of AGE staining in mucosa of all segments and RAGE staining in neurons in all
      segments were strongest in the diabetes group. Significant difference for AGE was
      found in the epithelial cells of villi and crypt in duodenum (immuno-positive
      area/total measuring area %: 13.37 +/- 3.51 vs 37.48 +/- 8.43, P < 0.05 for
      villi; 0.38 +/- 0.12 vs 1.87 +/- 0.53, P < 0.05 for crypt) and for RAGE in
      neurons of all segments (e.g., for jejunum: no staining neurons% 0 vs 0, mild
      36.0 +/- 5.2 vs 28.7 +/- 3.5, moderate 53.2 +/- 4.8 vs 55.8 +/- 5.4, strong 10.7
      +/- 1.1 vs 15.4 +/- 2.0, P < 0.05). In the colon, RAGE was primarily found in
      neurons in the myenteric and submucosal plexus. It was stronger in the diabetes
      group than in the normal group (no staining neurons% 6.2 +/- 0.2 vs 0.3 +/- 0.04,
      mild 14.9 +/- 2.1 vs 17.6 +/- 1.5, moderate 53.1 +/- 4.6 vs 44.7 +/- 4.4, strong
      25.6 +/- 18 vs 43.6 +/- 4.0, P < 0.05). In the rectum, RAGE was primarily found
      in the mucosa epithelial cells. CONCLUSION: The AGE and RAGE expression was up
      regulated in the GI tract of GK diabetic rats and may contribute to GI
      dysfunction in type 2 diabetic patients.

PMID- 25987964
TI  - Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2
      diabetes and metabolic syndrome.
AB  - Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are the serious
      public health problems worldwide. Moreover, it is estimated that MetS patients
      have about five-fold greater risk of the T2DM development compared with people
      without the syndrome. Peroxisome proliferator-activated receptors are a subgroup
      of the nuclear hormone receptor superfamily of ligand-activated transcription
      factors which play an important role in the pathogenesis of MetS and T2DM. All
      three members of the peroxisome proliferator-activated receptor (PPAR) nuclear
      receptor subfamily, PPARalpha, PPARbeta/delta and PPARgamma are critical in
      regulating insulin sensitivity, adipogenesis, lipid metabolism, and blood
      pressure. Recently, more and more studies indicated that the gene polymorphism of
      PPARs, such as Leu(162)Val and Val(227)Ala of PPARalpha, +294T > C of
      PPARbeta/delta, Pro(12)Ala and C1431T of PPARgamma, are significantly associated
      with the onset and progressing of MetS and T2DM in different population
      worldwide. Furthermore, a large body of evidence demonstrated that the glucose
      metabolism and lipid metabolism were influenced by gene-gene interaction among
      PPARs genes. However, given the complexity pathogenesis of metabolic disease, it
      is unlikely that genetic variation of a single locus would provide an adequate
      explanation of inter-individual differences which results in diverse clinical
      syndromes. Thus, gene-gene interactions and gene-environment interactions
      associated with T2DM and MetS need future comprehensive studies. 

PMID- 25987966
TI  - Temperature dependent dynamics of DegP-trimer: A molecular dynamics study.
AB  - DegP is a heat shock protein from high temperature requirement protease A family,
      which reacts to the environmental stress conditions in an ATP independent way.
      The objective of the present analysis emerged from the temperature dependent
      functional diversity of DegP between chaperonic and protease activities at
      temperatures below and above 28  degrees C, respectively. DegP is a multimeric
      protein and the minimal functional unit, DegP-trimer, is of great importance in
      understanding the DegP pathway. The structural aspects of DegP-trimer with
      respect to temperature variation have been studied using molecular dynamics
      simulations (for 100 ns) and principal component analysis to highlight the
      temperature dependent dynamics facilitating its functional diversity. The DegP
      trimer revealed a pronounced dynamics at both 280 and 320 K, when compared to the
      dynamics observed at 300 K. The LA loop is identified as the highly flexible
      region during dynamics and at extreme temperatures, the residues 46-80 of LA loop
      express a flip towards right (at 280) and left ( at 320 K) with respect to the
      fixed beta-sheet connecting the LA loop of protease for which Phe46 acts as one
      of the key residues. Such dynamics of LA loop facilitates inter-monomeric
      interaction with the PDZ1 domain of the neighbouring monomer and explains its
      active participation when DegP exists as trimer. Hence, the LA loop mediated
      dynamics of DegP-trimer is expected to provide further insight into the
      temperature dependent dynamics of DegP towards the understanding of its assembly
      and functional diversity in the presence of substrate. 

PMID- 25987967
TI  - Structures to complement the archaeo-eukaryotic primases catalytic cycle
      description: What's next?
AB  - DNA replication is a crucial stage in the transfer of genetic information from
      parent to daughter cells. This mechanism involves multiple proteins with one key
      player being the primase. Primases are single-stranded DNA dependent RNA
      polymerases. On the leading strand, they synthesize the primer once allowing DNA
      elongation while on the lagging strand primers are generated repeatedly (Okazaki
      fragments). Primases have the unique ability to create the first phosphodiester
      bond yielding a dinucleotide which is initially elongated by primases and then by
      DNA polymerases. Primase activity has been studied in the last decades but the
      detailed molecular steps explaining some unique features remain unclear. High
      resolution structures of free and bound primases domains have brought significant
      insights in the understanding of the primase reaction cycle. Here, we give a
      short review of the structural work conducted in the field of archaeo-eukaryotic
      primases and we underline the missing "pictures" of the active forms of the
      enzyme which are of major interest. We organized our analysis with respect to the
      progression through the catalytic pathway. 

PMID- 25987968
TI  - The role of low-level laser in periodontal surgeries.
AB  - Treatment protocols with low-level Laser (also called 'soft laser therapy) have
      been used in health care systems for more than three decades. Bearing in mind the
      suitable sub-cellular absorption and the cellular-vascular impacts, low-level
      laser may be a treatment of choice for soft tissues. Low-level lasers have played
      crucial and colorful roles in performing periodontal surgeries. Their anti
      inflammatory and painless effects have been variously reported in in-vitro
      studies. In this present review article, searches have been made in Pub Med,
      Google Scholar, and Science Direct, focusing on the studies which included low
      level lasers, flap-periodontal surgeries, gingivectomy, and periodontal graft.
      The present study has sought to review the cellular impacts of low-level lasers
      and its role on reducing pain and inflammation following soft tissue surgical
      treatments. 

PMID- 25987970
TI  - Effect of Different Powers of Er,Cr:YSGG Laser Treatment on Surface Morphology of
      Microhybride Composite Resin: Scanning Electron Microscope (SEM) Evaluation.
AB  - INTRODUCTION: The aim of this study was to evaluate and compare microhybride
      composite treated by bur and different power of Erbium, Chromium doped Yttrium
      Scandium Gallium Garnet (Er,Cr:YSGG) laser by Scanning Electron Microscope (SEM).
      METHODS: 21 microhybride composite blocks (DiaFil TM, DiaDent, Korea) with 2 * 4
      * 4 mm dimensions were made. The bonding surface of these blocks were polished,
      The samples were put into 6 groups for laser irradiation as follows: Group 1
      (power: 1W, Energy: 50 mJ); Group 2(power: 2 W, Energy: 100mJ); Group 3 (power:
      3W, Energy: 150mJ); Group 4 (power: 4W, Energy: 200mJ); Group 5 (power: 5W,
      Energy: 250mJ) and Group 6(power:6 W, Energy:300mJ). One group prepared by bur-
      treated. All samples were prepared by repetition rate of 20 Hz. Then, the samples
      were prepared for SEM examination. RESULT: Some irregularities were seen in
      Er,Cr:YSGG laser samples in comparison to Bur group that produced favorable
      surface for adhesion of repair composite. CONCLUSION: Among different lasers,
      Er;Cr:YSGG laser can be chosen as a suitable technique for surface treatment of
      unsatisfactory composites.

PMID- 25987969
TI  - Role of optical spectroscopic methods in neuro-oncological sciences.
AB  - In the surgical treatment of malignant tumors, it is crucial to characterize the
      tumor as precisely as possible. The determination of the exact tumor location as
      well as the analysis of its properties is very important in order to obtain an
      accurate diagnosis as early as possible. In neurosurgical applications, the
      optical, non-invasive and in situ techniques allow for the label-free analysis of
      tissue, which is helpful in neuropathology. In the past decades, optical
      spectroscopic methods have been investigated drastically in the management of
      cancer. In the optical spectroscopic techniques, tissue interrogate with sources
      of light which are ranged from the ultraviolet to the infrared wavelength in the
      spectrum. The information accumulation of light can be in a reflection which is
      named reflectance spectroscopy; or interactions with tissue at different
      wavelengths which are called fluorescence and Raman spectroscopy. This review
      paper introduces the optical spectroscopic methods which are used to characterize
      brain tumors (neuro-oncology). Based on biochemical information obtained from
      these spectroscopic methods, it is possible to identify tumor from normal brain
      tissues, to indicate tumor margins, the borders towards normal brain tissue and
      infiltrating gliomas, to distinguish radiation damage of tissues, to detect
      particular central nervous system (CNS) structures to identify cell types using
      particular neurotransmitters, to detect cells or drugs which are optically
      labeled within therapeutic intermediations and to estimate the viability of
      tissue and the prediction of apoptosis beginning in vitro and in vivo. The label
      free, optical biochemical spectroscopic methods can provide clinically relevant
      information and need to be further exploited to develop a safe and easy-to-use
      technology for in situ diagnosis of malignant tumors. 

PMID- 25987971
TI  - Qualitative analysis of teeth and evaluation of amalgam elements penetration into
      dental matrix using laser induced breakdown spectroscopy.
AB  - INTRODUCTION: In this study, laser induced breakdown spectroscopy (LIBS) is used
      for qualitative analysis of healthy and carious teeth. The technique of laser
      ablation is receiving increasing attention for applications in dentistry,
      specifically for the treatment of teeth such as drilling of micro-holes and
      plaque removal. METHODS: A quality-switched (Q-switched) Neodymium-Doped Yttrium
      Aluminium Garnet (Nd:YAG) laser operating at wavelength of 1064 nm, pulse energy
      of 90 mJ/pulse, repetition rate of 2Hz and pulse duration of 6 ns was used in
      this analysis. In the process of ablation a luminous micro-plasma is normally
      generated which may be exploited for on-line elemental analysis via laser induced
      breakdown spectroscopy technique. We propose laser induced breakdown spectroscopy
      as a rapid, in situ and easy method for monitoring drilling process. RESULTS: The
      results of elemental analysis show the presence of some trace elements in teeth
      including P, Ca, Mg, Zn, K, Sr, C, Na, H, O and the permeability of some amalgam
      (teeth filling materials) elements including Hg, Ag, Cu and Sn into dental
      matrix. CONCLUSION: This study addresses the ability of LIBS in elemental
      analysis of teeth and its feasibility in acute identification of healthy and
      carious teeth during drilling process for future clinical applications.

PMID- 25987972
TI  - The effect of low-level laser therapy on human leukemic cells.
AB  - INTRODUCTION: Laser phototherapy is used for the treatment of chemotherapy
      induced oral mucositis in patients with leukemia, although there are limited data
      supporting the safety of this method. This study aimed to evaluate the effect of
      different doses of low-level laser on proliferation of acute myeloid leukemia
      (AML) cell line (KG-1a) in vitro. METHODS: A plastic flask containing 5,000,000
      KG-1a cultured cells was provided by Iran Pasteur Institute. KG-1a cell line has
      been produced from the bone marrow aspirate of a 59-year-old white male with
      acute myelogenous leukemia. Upon completion of the proliferation steps of KG-1a
      cell line, 7*10(4) cells were placed in 96-well tissue culture plates. All the
      surrounding wells were filled with Wright-Giemsa stain in order to prevent laser
      from scattering to the neighboring wells. In total, 28 plates were prepared using
      this method. After a forty-eight hours incubation period, irradiation was
      performed in continuous mode with an infrared laser of 810nm wavelength. After 24
      hours, cells cultures were exposed to one, two, or three applications of laser
      irradiation. Irradiation exposures were performed at energy densities of 5, 10,
      and 20 J/cm(2) . Each experiment included 18 replicates for each application of
      laser and 6 replicates of negative/untreated controls. For experiments with two
      and three repeated exposures, the irradiation applications were separated by 48
      hours. All the culture plates were incubated for seven days. Cell proliferation
      was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl
      tetrazolium bromide) assay after seven days. Spectroscopy (620nm) was used to
      determine the optical density (OD) of both irradiated and control samples.
      RESULTS: Significant increase in cell proliferation was seen only after two
      exposures at energy density of 20J/cm2 (P=0.021). CONCLUSION: Although LLLT is
      commonly used to treat radiotherapy- or chemotherapy- induced mucositis, as long
      as further studies demonstrate that different wavelengths and doses of laser
      phototherapy are safe and effective in treatment of mucositis, clinicians should
      remain cautious regarding the use of this treatment modality to treat patients
      with malignancies.

PMID- 25987973
TI  - Scanning Electron Microscope (SEM) Evaluation of Composite Surface Irradiated by
      Different Powers of Er:YAG Laser.
AB  - INTRODUCTION: The aim of this study was to evaluate the composite surface treated
      by different powers of Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) laser in
      comparison with bur preparation via scanning electron microscope. METHODS:
      Fourteen composite resin blocks with 15* 10 * 10 mm dimensions were used in this
      study. The samples were divided to seven groups as follow: Group 1 (power: 1 W,
      Energy: 50 mJ); Group 2 (power: 2 W, Energy: 100 mJ); Group 3 (power: 3W, Energy:
      150 mJ); Group 4 (power: 4 W, Energy: 200 mJ); Group 5 (power: 5W, Energy: 250
      mJ); Group 6 (power: 6 W, Energy: 300 mJ); Group 7: Diamond bur. Then, the
      samples were prepared for SEM examination. RESULTS: The surface treated by Er:YAG
      laser showed irregular and micro porous surface. CONCLUSION: It seems that
      composite surface treatment by Er:YAG laser can be an alternative method for
      composite repair if suitable parameters are used.

PMID- 25987974
TI  - Evaluation of the effect of low level laser therapy toothbrush in treatment of
      dentin hypersensitivity.
AB  - INTRODUCTION: Dentin hypersensitivity is one of the most common complications
      that affect patients after periodontal therapy. Recently low level laser therapy
      has been introduced as a new treatment modality and has produced beneficial
      results. The purpose of this study is to evaluate the effect of low level laser
      therapy toothbrushes in reduction of dentin hypersensitivity. METHODS: In this
      pilot interventional controlled clinical trial, 40 patients suffering from dentin
      hypersensitivity were selected using simple randomization. Half of the patients
      were given laser toothbrushes and the other half was given non-laser sensodyne
      toothbrushes. Primary dentin hypersensitivity was recorded by visual analogue
      scale (VAS) score and ice spray. Then dentin hypersensitivity was measured right
      after the treatment as well az in the intervals of 1 month and 2 months after
      initiation of the study. Data were compared using Statistical Package for the
      Social Sciences (SPSS) software and Analysis of variance (ANOVA) paired T test.
      RESULTS: The results of this study showed that there was a significant difference
      in each of the two kinds of tooth brushes separately for all time intervals (P <
      0.001). Also the effect of the type of toothbrush was investigated using before
      treatment VAS with covariance analyses. P values for immediately, 1 month and 2
      months after treatment were calculated to be 0.078, 0.02, 0.01 respectfully. Also
      the effect of the toothbrush type was significant in the manner that laser
      toothbrushes reduce dentin hypersensitivity more than ordinary toothbrushes (P<
      0.05). CONCLUSION: Both sensodyne and laser tooth brushes improve dentin
      hypersensitivity, although the laser toothbrush led to better results in short.

PMID- 25987975
TI  - Excision of epulis granulomatosa with diode laser in 8 years old boy.
AB  - INTRODUCTION: Epulis granulomatosa is a lesion which grows from an extraction
      socket. It can be misdiagnosed with lesions of the same clinical appearance such
      as: foreign body or pyogenic granuloma, or as a herniation of the maxillary
      sinus. The most common treatment is surgical excision. CASE REPORT: The present
      article reports an Epulis granulomatosa which was removed with diode laser (810
      nm) due to child's fear related to traditional surgical instruments and bleeding.
      RESULTS AND CONCLUSION: Lasers are useful for soft tissue surgery in modern
      dentistry, especially in relation to pediatric patients due to the rapid and
      regular wound healing without sutures.

PMID- 25987976
TI  - Neural growth hormone: regional regulation by estradiol and/or sex chromosome
      complement in male and female mice.
AB  - BACKGROUND: Sex differences in pituitary growth hormone (GH) are well documented
      and coordinate maturation and growth. GH and its receptor are also produced in
      the brain where they may impact cognitive function and synaptic plasticity, and
      estradiol produces Gh sex differences in rat hippocampus. In mice, circulating
      estradiol increases Gh mRNA in female but not in male medial preoptic area
      (mPOA); therefore, additional factors regulate sexually dimorphic Gh expression
      in the brain. Thus, we hypothesized that sex chromosomes interact with estradiol
      to promote sex differences in GH. Here, we assessed the contributions of both
      estradiol and sex chromosome complement on Gh mRNA levels in three large brain
      regions: the hippocampus, hypothalamus, and cerebellum. METHODS: We used the four
      core genotypes (FCG) mice, which uncouple effects of sex chromosomes and gonadal
      sex. The FCG model has a deletion of the sex-determining region on the Y
      chromosome (Sry) and transgenic insertion of Sry on an autosome. Adult FCG mice
      were gonadectomized and given either a blank Silastic implant or an implant
      containing 17beta-estradiol. Significant differences in GH protein and mRNA were
      attributed to estradiol replacement, gonadal sex, sex chromosome complement, and
      their interactions, which were assessed by ANOVA and planned comparisons.
      RESULTS: Estradiol increased Gh mRNA in the cerebellum and hippocampus,
      regardless of sex chromosome complement or gonadal sex. In contrast, in the
      hypothalamus, females had higher Gh mRNA than males, and XY females had more Gh
      mRNA than XY males and XX females. This same pattern was observed for GH protein.
      Because the differences in Gh mRNA in the hypothalamus did not replicate prior
      studies using other mouse models and tissue from mPOA or arcuate nucleus, we
      examined GH protein in the arcuate, a subdivision of the hypothalamus. Like the
      previous reports, and in contrast to the entire hypothalamus, a sex chromosome
      complement effect showed that XX mice had more GH than XY in the arcuate.
      CONCLUSIONS: Sex chromosome complement regulates GH in some but not all brain
      areas, and within the hypothalamus, sex chromosomes have cell-specific actions on
      GH. Thus, sex chromosome complement and estradiol both contribute to GH sex
      differences in the brain.

PMID- 25987978
TI  - A phase II trial to assess the activity of gemcitabine and docetaxel as first
      line chemotherapy treatment in patients with unresectable leiomyosarcoma.
AB  - BACKGROUND: Gemcitabine and docetaxel have been shown to be active in pre-treated
      relapsed leiomyosarcoma. This study investigated the combination as first line
      treatment in patients with unresectable locally advanced/metastatic
      leiomyosarcoma. METHODS: Patients received gemcitabine 900 mg/m(2) days 1 and 8,
      and docetaxel 100 mg/m(2) day 8, administered 3-weekly for up to 8 cycles, with
      GCSF support on days 9-15. Patients who had received previous radiotherapy were
      treated at 75% dose. Patients were evaluated for response by RECIST 1.0 after
      cycles 2, 4, 6 and 8, and 3-monthly after completing treatment. RESULTS: Forty
      four patients were evaluable for response. Eligible patients had histologically
      proven leiomyosarcoma of the uterus (54.5%) or other sites (45.5%). Thirty-nine
      patients (84.4%) had metastatic disease, and 5 (15.6%) had locally advanced
      disease. Six patients (13.6%) had grade 1 disease, and 23 (75%) had grade 2/3
      disease. All patients had demonstrated disease progression prior to trial entry.
      Responses were as follows: partial response 11 (25.0%), stable disease
      (confirmed) 16 (36.6%), stable disease (unconfirmed) 7 (15.9%), progressive
      disease 10 (22.7%). Median progression-free survival and overall survival were
      7.1 months (95% CI 5.7-8.3) and 17.9 months (95% CI 10.6-25.2), respectively.
      Progression free rates at 3 and 6 months were 70.5% (95% CI 56.7-84.2%) and 59.1%
      (95% CI 44.3-73.9%). CONCLUSIONS: This study demonstrates gemcitabine and
      docetaxel to be active in locally advanced/metastatic leiomyosarcoma in the first
      line setting. Further investigation comparing with current standard therapies for
      leiomyosarcoma is warranted.

PMID- 25987979
TI  - Emerging Toxicity Models from Emerging Scientists.
AB  - Toxicology has seen a recent influx of new talents from other fields attracted by
      the application of their expertise to pressing questions of toxicological and
      environmental relevance. This transition has opened the door to innovative and
      exciting scientific opportunities but has also generated a new set of questions
      and challenges. In this viewpoint article, I will highlight some of the drivers
      and hurdles encountered by the recent new breeds of toxicologists.

PMID- 25987977
TI  - Muscular dystrophy in the mdx mouse is a severe myopathy compounded by
      hypotrophy, hypertrophy and hyperplasia.
AB  - BACKGROUND: Preclinical testing of potential therapies for Duchenne muscular
      dystrophy (DMD) is conducted predominantly of the mdx mouse. But lack of a
      detailed quantitative description of the pathology of this animal limits our
      ability to evaluate the effectiveness of putative therapies or their relevance to
      DMD. METHODS: Accordingly, we have measured the main cellular components of
      muscle growth and regeneration over the period of postnatal growth and early
      pathology in mdx and wild-type (WT) mice; phalloidin binding is used as a measure
      of fibre size, myonuclear counts and BrdU labelling as records of myogenic
      activity. RESULTS: We confirm a two-phase postnatal growth pattern in WT muscle:
      first, increase in myonuclear number over weeks 1 to 3, then expansion of
      myonuclear domain. Mdx muscle growth lags behind that of WT prior to overt signs
      of pathology. Fibres are smaller, with fewer myonuclei and smaller myonuclear
      domains. Moreover, satellite cells are more readily detached from mdx than WT
      muscle fibres. At 3 weeks, mdx muscles enter a phase of florid myonecrosis,
      accompanied by concurrent regeneration of an intensity that results in complete
      replacement of pre-existing muscle over the succeeding 3 to 4 weeks. Both WT and
      mdx muscles attain maximum size by 12 to 14 weeks, mdx muscle fibres being up to
      50% larger than those of WT as they become increasingly branched. Mdx muscle
      fibres also become hypernucleated, containing twice as many myonuclei per
      sarcoplasmic volume, as those of WT, the excess corresponding to the number of
      centrally placed myonuclei. CONCLUSIONS: The best-known consequence of lack of
      dystrophin that is common to DMD and the mdx mouse is the conspicuous necrosis
      and regeneration of muscle fibres. We present protocols for measuring this in
      terms both of loss of muscle nuclei previously labelled with BrdU and of the
      intensity of myonuclear labelling with BrdU administered during the regeneration
      period. Both measurements can be used to assess the efficacy of putative
      antinecrotic agents. We also show that lack of dystrophin is associated with a
      number of previously unsuspected abnormalities of muscle fibre structure and
      function that do not appear to be directly associated with myonecrosis.

PMID- 25987980
TI  - Hip and knee arthroplasty: quo vadis?
AB  - Despite of the steady decrease of surgical site infection (SSI) over the last two
      decades, the incidence of SSI after hip and knee arthroplasty has recently
      surged. This may be explained by technical changes that may result in an
      increased risk of SSI, such as the broad implementation of fast track programs,
      and/or early interventions on suspected SSI. By definition, early intervention
      may lead to a higher SSI score, even in the absence of a true SSI. In any case,
      the reverse trend of SSI warrants further investigations. 

PMID- 25987981
TI  - Abaloparatide: a new anabolic therapy on the horizon.

PMID- 25987982
TI  - Structural differences in epiphyseal and physeal hypertrophic chondrocytes.
AB  - We have observed that epiphyseal and physeal hypertrophic chondrocytes in BALB/c
      mice show considerable differences of light microscopic and ultrastructural
      appearance, even when the cells are at the same stage of differentiation. In
      addition, cell structure maintenance improved with tissue preparation controlled
      for osmolarity and for membrane stabilization using 0.5% ruthenium hexammine
      trichloride (RHT) for both light microscopy (LM) and electron microscopy (EM) or
      0.5% lanthanum nitrate for LM. Physeal hypertrophic chondrocytes showed a gradual
      increase in size closer to the metaphysis and a change in shape as cells
      elongated along the long axis. The nucleus remained central, with uniformly
      dispersed chromatin, and the rough endoplasmic reticulum (RER) was randomly
      dispersed throughout cytoplasm with little to no presence against the cell
      membrane. Even the lowermost cells showed thin elongated or dilated cisternae of
      RER and intact cell membranes. Epiphyseal chondrocytes remained circular to oval
      with no elongation. Nucleus and RER were positioned as a complete transcellular
      central nucleocytoplasmic column or as an incomplete bud with RER of the
      column/bud always continuous with RER peripherally against the intact cell
      membrane. RER was densely packed with parallel cisternae with adjacent cytoplasm
      empty of organelles but often filled with circular deposits of moderately
      electron-dense material consistent with fat. Optimal technique for LM involved
      fixation using glutaraldehyde (GA) 1.3%, paraformaldehyde (PFA) 1% and RHT 0.5%
      (mOsm 606) embedded in JB-4 plastic and stained with 0.5% toluidine blue. Optimal
      technique for EM used fixation with GA 1.3%, PFA 1%, RHT 0.5% and cacodylate
      buffer 0.03 M (mOsm 511) and post-fixation including 1% osmium tetroxide. These
      observations lead to the possibility that the same basic cell, the hypertrophic
      chondrocyte, has differing functional mechanisms at different regions of the
      developing bone. 

PMID- 25987983
TI  - Screening for vitamin D deficiency in adults.

PMID- 25987984
TI  - A new WNT on the bone: WNT16, cortical bone thickness, porosity and fractures.
AB  - The last decade has provided abundant data implicating the WNT pathway in bone
      development and in the regulation of skeletal homeostasis. Rare human mutations
      together with gain- and loss-of-function approaches in mice have clearly
      demonstrated that disrupted regulation of this pathway leads to altered bone
      mass. In addition to these rare human and mice mutations, large population-based
      genome-wide association studies (GWASs) have identified single-nucleotide
      polymorphisms in ~60 loci strongly associated with variations in bone mineral
      density (BMD) at different skeletal sites. Among the loci/genes identified by BMD
      GWAS, components of the WNT signaling pathway are numerous and have been shown to
      contribute to skeletal development and homeostasis. Within the components of WNT
      signaling, the gene coding for WNT16, one of the 19 WNT ligands of the human
      genome, has been found strongly associated with specific bone traits such as
      cortical bone thickness, cortical porosity and fracture risk. Recently, the first
      functional characterization of Wnt16 has confirmed the critical role of Wnt16 in
      the regulation of cortical bone mass and bone strength in mice. These reports
      have extended our understanding of Wnt16 function in bone homeostasis and have
      not only confirmed the unique association of Wnt16 with cortical bone and
      fracture susceptibility, as suggested by GWAS in human populations, but have also
      provided novel insights into the biology of this WNT ligand and the mechanism(s)
      by which it regulates cortical but not trabecular bone homeostasis. Most
      interestingly, Wnt16 appears to be a strong anti-resorptive soluble factor acting
      on both osteoblasts and osteoclast precursors. 

PMID- 25987985
TI  - Preclinical mouse models of osteosarcoma.
AB  - Osteosarcoma is the most common form of primary bone tumors with high prevalence
      in children. Survival rates of osteosarcoma are low, especially in the case of
      metastases. Mouse models of this disease have been very valuable in investigation
      of mechanisms of tumorigenesis, metastasis, as well as testing possible
      therapeutic options. In this chapter, we summarize currently available mouse
      models for osteosarcoma and provide detailed methodology for the isolation of
      cell lines from genetically engineered mouse models (GEMMs), gene modification
      and tumor cell injection methods, as well as imaging techniques. 

PMID- 25987987
TI  - Tumour-derived miRNAs and bone metastasis.
AB  - Skeletal metastases are complications of epithelial cancers, among which breast,
      prostate and lung carcinomas are the most osteotropic. In primary tumours, a
      subset of cancer cells undergoes epithelial-mesenchymal transition, acquires
      mobility to migrate into the surrounding stroma and seeds at distant sites to
      grow. The specific development of bone metastasis requires the recruitment of
      circulating tumour cells in the bone marrow, their adaptation to survive in the
      surrounding microenvironment where they alter the functions of osteoclasts and
      osteoblasts, and hijack signals coming from the bone matrix. Each of the
      molecular pathways underlining these steps is regulated by multiple factors,
      through the tight control of genes expressed by cancer cells interacting with
      cells from the bone microenvironment. In this context, miRNAs can act as master
      regulators of gene expression to control multiple aspects of bone metastasis
      formation, including cancer cell escape from the primary tumour site, cancer cell
      dissemination to bone and invasion of the bone marrow, as well as secondary
      outgrowth and tumour-stroma cell interactions. In the clinic, specific miRNA
      signatures have been identified in osteotropic cancer cells, raising the
      possibility that miRNAs could be used as biomarkers of bone metastasis. The
      regulatory activity of miRNAs in the bone microenvironment also suggests that
      miRNAs could be promising therapeutic targets. 

PMID- 25987990
TI  - Better food safety practices.

PMID- 25987986
TI  - The role of fetuin-A in mineral trafficking and deposition.
AB  - Calcium and phosphate are the principle ions involved in the deposition of
      mineral in the human body. Inhibitors of mineralisation are essential for the
      prevention of ectopic mineral precipitation and deposition. In the past decade,
      through in vitro, in vivo and clinical observation studies, we have come to
      appreciate the importance of fetuin-A (Fet-A), a circulating glycoprotein, in
      preventing ectopic calcium phosphate mineralisation. Moreover, the detection of
      Fet-A-containing mineral complex, termed calciprotein particles (CPPs), has
      provided new ways to assess an individual's calcific risk. The pathophysiological
      significance of CPPs in disease states is yet to be defined, but it provides an
      exciting avenue to further our understanding of the development of ectopic
      mineralisation. 

PMID- 25987988
TI  - Acidic microenvironment and bone pain in cancer-colonized bone.
AB  - Solid cancers and hematologic cancers frequently colonize bone and induce
      skeletal-related complications. Bone pain is one of the most common complications
      associated with cancer colonization in bone and a major cause of increased
      morbidity and diminished quality of life, leading to poor survival in cancer
      patients. Although the mechanisms responsible for cancer-associated bone pain
      (CABP) are poorly understood, it is likely that complex interactions among cancer
      cells, bone cells and peripheral nerve cells contribute to the pathophysiology of
      CABP. Clinical observations that specific inhibitors of osteoclasts reduce CABP
      indicate a critical role of osteoclasts. Osteoclasts are proton-secreting cells
      and acidify extracellular bone microenvironment. Cancer cell-colonized bone also
      releases proton/lactate to avoid intracellular acidification resulting from
      increased aerobic glycolysis known as the Warburg effect. Thus, extracellular
      microenvironment of cancer-colonized bone is acidic. Acidosis is algogenic for
      nociceptive sensory neurons. The bone is densely innervated by the sensory
      neurons that express acid-sensing nociceptors. Collectively, CABP is evoked by
      the activation of these nociceptors on the sensory neurons innervating bone by
      the acidic extracellular microenvironment created by bone-resorbing osteoclasts
      and bone-colonizing cancer cells. As current treatments do not satisfactorily
      control CABP and can elicit serious side effects, new therapeutic interventions
      are needed to manage CABP. Understanding of the cellular and molecular mechanism
      by which the acidic extracellular microenvironment is created in cancer-colonized
      bone and by which the expression and function of the acid-sensing nociceptors on
      the sensory neurons are regulated would facilitate to develop novel therapeutic
      approaches for the management of CABP. 

PMID- 25987989
TI  - Chronic stress, sympathetic activation and skeletal metastasis of breast cancer
      cells.
AB  - Improved detection programs and new therapies significantly improved the 5-year
      survival rate of women with breast cancer. However, some women still relapse and
      succumb to cancer because of metastatic disease. In particular, chronically
      depressed patients do not seem to benefit from newly developed treatments and
      present with shorter survival. The reason for this association is unclear, but
      recent cues from preclinical studies point to the possible contribution of
      neuroendocrine factors generated in response to chronic stress and depression.
      Retrospective clinical studies also suggest a beneficial effect of sympathetic
      blockade in terms of less advanced disease at diagnosis, lower cancer-specific
      mortality, longer disease-free survival and reduced metastasis development and
      tumor recurrence, especially in patients who have taken propranolol before
      diagnosis. Therefore, beta-blockers or therapies normalizing sympathetic tone
      might be beneficial as early adjuvant therapies to limit skeletal metastases and
      growth and eventually to improve prognosis in patients with breast cancers. 

PMID- 25987991
TI  - Determination of biogenic amines by high-performance liquid chromatography (HPLC
      DAD) in probiotic cow's and goat's fermented milks and acceptance.
AB  - This study evaluated the presence of biogenic amines in fermented cow's and
      goat's milks containing probiotic bacteria, during the first 10 days of chilled
      storage (4 +/- 2 degrees C), when the probiotic strains are most viable. The
      overall acceptance of both fermented milks, produced using the same starter
      culture and probiotics, was tested. In both products, the initially high levels
      of tyramine (560 mg kg(-1) means for both fermented milks), the predominant
      biogenic amine, increased during the storage period, which may be considered this
      amine as a quality index for fermented milks. The other principal biogenic amines
      (putrescine, cadaverine, histamine, and spermidine) were produced on days 1-5 of
      storage, and thereafter decreased. At the end of the 10th day, these amines,
      respectively, showed values of fermented cow's milk 20.26, 29.09, 17.97, and
      82.07 mg kg(-1); and values of fermented goat's milk 22.92, 29.09, 34.85, and
      53.85 mg kg(-1), in fermented cow's and goat's milk. Fermented cow's milk was
      well accepted compared to fermented goat's milk. The results suggested that the
      content of biogenic amines may be a criterion for selecting lactic acid bacteria
      used to produce fermented milks. 

PMID- 25987992
TI  - Influence of extraction techniques on antioxidant properties and bioactive
      compounds of loquat fruit (Eriobotrya japonica Lindl.) skin and pulp extracts.
AB  - In this study, the bioactive compounds of loquat fruit (Eriobotrya japonica
      Lindl.) skin and pulp extracted by two extraction methods (solvent and ultrasound
      assisted) with three solvents (ethanol, water and ethanol-water) were compared to
      supercritical fluid extraction. The antioxidant activities of skin and pulp
      extracts were evaluated and compared to tertiary butylhydroquinone (TBHQ) using
      2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, beta-carotene
      bleaching, and the Rancimat assays. In DPPH assay solvent extracts of skin by
      ethanol (SSE) and ethanol-water (SSEW) showed strong inhibitory activity. The
      SSEW also showed the highest inhibition percentage of 85.58% by the beta-carotene
      bleaching assay and longest induction time of 4.78 h by the Rancimat method. The
      large amount of tocopherols and phenolics contained in the skin extract may cause
      its strong antioxidant ability. The results indicated that the solvent extraction
      with ethanol-water produced the maximum extraction yield of phenolic and
      tocopherol compounds from loquat fruit skin and pulp. Furthermore, solvent
      extraction was the most effective in antioxidant activity of the extracts
      compared to other extraction techniques. 

PMID- 25987993
TI  - Effect of sodium alginate coating enriched with horsemint (Mentha longifolia)
      essential oil on the quality of bighead carp fillets during storage at 4 degrees
      C.
AB  - Effect of sodium alginate coating enriched with horsemint essential oil (HEO) on
      the quality of bighead carp (Aristichthys nobilis) fillets at refrigeration
      temperature (4 +/- 1 degrees C) was studied. Bighead carp fillets were coated
      with neat sodium alginate (SA) and sodium alginate containing 0.5 and 1% v/v of
      HEO and their quality changes in terms of total volatile basic nitrogen (TVB-N),
      peroxide value (PV), thiobarbituric acid (TBA), and microbial counts were
      investigated. SA coating enriched with the essential oil could reduce the
      spoilage of the fillets and extend their shelf-life. Samples treated with SA
      containing HEO showed significantly (P < 0.05) lower TVB-N content and lipid
      oxidation, as reflected by lower PV, FFA and TBA values during the storage period
      compared with the SA and control. The treatment also reduced the degree of
      microbial deterioration of the fillets (about 1.5 log10 CFU/g) more efficiently
      than the SA. 

PMID- 25987994
TI  - Absorption of omega-3 fats from carbohydrate and proteinaceous food matrices
      before and after storage.
AB  - Development of n-3 fortified, shelf-stable foods is facilitated by encapsulated
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), since natural n-3
      food sources cannot withstand high temperature and prolonged shelf life.
      Organoleptic stability of n-3 fortified, shelf-stable foods has been
      demonstrated, but chemical changes in the food matrix throughout storage could
      conceivably impact digestibility of the protein-based encapsulant thereby
      compromising n-3 bioavailability. We assessed the effect of prolonged high
      temperature storage and variations in food matrix (proteinaceous or carbohydrate)
      on the time course and magnitude of blood fatty acids changes associated with
      ingestion of n-3 fortified foods. Low-protein (i.e., cake) and high-protein
      (i.e., meat sticks) items were supplemented with 600 mg encapsulated DHA+EPA, and
      frozen either immediately after production (FRESH) or after 6 months storage at
      100 degrees F (STORED). Fourteen volunteers consumed one item per week
      (randomized) for 4 weeks. Blood samples obtained at baseline, 2, 4, and 6 h post
      consumption were analyzed for circulating long-chain omega 3 fatty acids (LCn3).
      There was no difference in LCn3 area under the curve between items. LCn3 in
      response to cakes peaked at 2-h (FRESH: 54.0 +/- 16.8 MUg/mL, +18%; STORED: 53.0
      +/- 13.2 MUg/mL, +20%), while meats peaked at 4-h (FRESH: 51.9 +/- 12.5 MUg/mL,
      +22%; STORED: 53.2 +/- 16.9 MUg/mL, +18%). There were no appreciable differences
      in time course or magnitude of n-3 appearance in response to storage conditions
      for either food types. Thus, bioavailability of encapsulated DHA/EPA, within low-
      and high-protein food items, was not affected by high-temperature shelf-storage.
      A shelf-stable, low- or high-protein food item with encapsulated DHA/EPA is
      suitable for use in shelf-stable foods. 

PMID- 25987995
TI  - Model for understanding consumer textural food choice.
AB  - The current paradigm for developing products that will match the marketing
      messaging is flawed because the drivers of product choice and satisfaction based
      on texture are misunderstood. Qualitative research across 10 years has led to the
      thesis explored in this research that individuals have a preferred way to
      manipulate food in their mouths (i.e., mouth behavior) and that this behavior is
      a major driver of food choice, satisfaction, and the desire to repurchase.
      Texture, which is currently thought to be a major driver of product choice, is a
      secondary factor, and is important only in that it supports the primary driver
      mouth behavior. A model for mouth behavior is proposed and the qualitative
      research supporting the identification of different mouth behaviors is presented.
      The development of a trademarked typing tool for characterizing mouth behavior is
      described along with quantitative substantiation of the tool's ability to group
      individuals by mouth behavior. The use of these four groups to understand
      textural preferences and the implications for a variety of areas including
      product design and weight management are explored. 

PMID- 25987996
TI  - Effects of types and amounts of stabilizers on physical and sensory
      characteristics of cloudy ready-to-drink mulberry fruit juice.
AB  - In this study, the pH of mulberry juice was optimized for high anthocyanin
      content and an attractive red color. Mulberry juice pH values of 2.5, 4.0, 6.0,
      and 8.0 were evaluated. A pH of 2.5 gave an anthocyanin content of 541.39 +/-
      106.43 mg of cyanidin-3-glucoside per liter, and the a* value was 14 +/- 1.00.
      The effects of stabilizers (CMC and xanthan gum) on the physical characteristics
      of cloudy ready-to-drink mulberry fruit juice (via the addition of mulberry fruit
      pulp at a mass fraction of 5%) during storage (4 degrees C for 1 week) were also
      determined using different mass fractions of the stabilizers (0.1%, 0.3%, and
      0.5%). Increasing the stabilizer mass fraction increased the viscosity,
      turbidity, stability of turbidity, and h* value. Using xanthan gum as the
      stabilizer produced better results for these parameters than CMC. The type of
      stabilizer and its mass fraction had no effect on most sensory characteristics,
      including appearance, color, taste, texture, and overall acceptability (P >=
      0.05), but did affect the odor (P >= 0.05). Xanthan gum stabilizer gave the juice
      a better odor than CMC. Cloudy mulberry juice containing 0.5% xanthan gum as the
      stabilizer had the highest acceptance rate among panelists (average acceptance
      was 6.90 +/- 1.37 points) and produced no precipitate during storage. 

PMID- 25987997
TI  - Morphological, physicochemical, and antioxidant profile of noncommercial banana
      cultivars.
AB  - Banana cultivars--Luvhele (MusaABB), Mabonde (MusaAAA), and Muomva-red (Musa
      balbisiana) --were characterized for morphological, physicochemical, and
      antioxidant properties. All three cultivars varied significantly (P < 0.05) in
      their morphology, pH, titratable acidity and total soluble solids with no
      significant difference in their ash content. Individual cultivars showed
      variations in flour starch granule when observed using a scanning electron
      microscope. Characterization of cultivars for total polyphenols (TPs) and
      antioxidant activity upon pretreatment with ascorbic, citric, and lactic acid
      shows that the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay of
      samples varied significantly as Muomva-red cultivar (1.02 +/- 0.01 mg GA/g)
      expressed the highest DPPH activity at lactic acid concentration of 20 g/L. Total
      polyphenol content was also highest for Muomva-red [1091.76 +/- 122.81 mg GAE/100
      g (d.w.)]. The high amount of TPs present in these cultivars make them suitable
      source of bio-nutrients with great medicinal and health functions. 

PMID- 25987998
TI  - Effects of combined traditional processing methods on the nutritional quality of
      beans.
AB  - Consumption of dry beans is limited by long cooking times thus high fuel
      requirement. The bioavailability of nutrients in beans is also limited due to
      presence of antinutrients such as phytates and tannins. Little research has been
      done on combined processing methods for production of nutritious fast cooking
      bean flour and the effect of combined treatments on nutritional quality of beans
      has not previously determined. The aim of this study was to reduce cooking time
      and enhance the nutritional value of dry beans. Specifically to: develop
      protocols for production of fast cooking bean flours and assess the effect of
      processing on the nutritional characteristics of the flours. Dry beans (K131
      variety) were soaked for 12 h; sprouted for 48 h; dehulled and steamed for 25 and
      15 min for whole and dehulled beans respectively or roasted at 170 degrees C for
      45 and 15 min for whole and dehulled beans respectively. Dehulling eliminated
      phytates and tannins and increased protein digestibility. In vitro protein
      digestibility and mineral (iron and zinc) extractability were negatively
      correlated with tannin and phytate content. Total available carbohydrates were
      highest in moist heat-treated bean flours. Overall, combined processing of beans
      improved the nutritional quality of dry beans and the resulting precooked flours
      need less cooking time compared to whole dry beans. 

PMID- 25987999
TI  - Antioxidative responses during germination in quinoa grown in vitamin B-rich
      medium.
AB  - Synthetic vitamin preparations have grown in popularity to combat health risks
      associated with an imbalanced diet, poor exercise and stress. In terms of
      bioavailability and diversity, they lack behind vitamins naturally occurring in
      plants. Solutions to obtain plant-derived vitamins at a larger scale are highly
      desirable. B vitamins act as precursors of enzymatic cofactors, thereby
      regulating important metabolic processes both in animals and plants. Because
      during plant germination, the vitamin content and micronutrient availability
      increase, sprouts are generally considered a healthier food as compared to dry
      grains. Germination only occurs if a plant's antioxidant machinery is
      sufficiently activated to cope with oxidative stress. Seeds of quinoa, an edible
      gluten-free plant naturally rich in minerals, germinate readily in a solution
      containing the eight B vitamins. We studied biochemical changes during quinoa
      germination, with a focus on nutritionally relevant characteristics. The results
      are considered from a nutritional and plant physiological perspective.
      Germination of quinoa in vitamin-rich medium is a promising strategy to enhance
      the nutritional value of this matrix. Additional health-beneficial effects
      indirectly resulting from the vitamin treatment include elevated levels of the
      multi-functional amino acid proline and a higher antioxidant capacity. Plant
      biomolecules can be better protected from oxidative damage in vivo. 

PMID- 25988000
TI  - Amino acid profile and oxidizable vitamin content of Synsepalum dulcificum berry
      (miracle fruit) pulp.
AB  - The amino acid profile of the Synsepalum dulcificum berry was studied. Among the
      essential amino acid observed, leucine (2.35 g/100 g protein) was the highest
      while methionine (0.31 g/100 g protein) was the lowest. The nonessential amino
      acids were also discovered, with glutamic acid (3.43 g/100 g protein) being the
      highest and glycine (0.38 g/100 g protein), the lowest. The study of the
      oxidizable vitamins revealed that vitamin C (1.33 mg/100 g) was more abundant
      than vitamin A (2.54 ug) and vitamin E (0.78 mg/100 g). This information will
      hopefully enhance the fruits acceptability by more people and thus, generally
      promote its utilization and appreciation in our diets. 

PMID- 25988003
TI  - Study of physio-psychological effects on traffic wardens due to traffic noise
      pollution; exposure-effect relation.
AB  - BACKGROUND: Noise pollution has increased to alarming extent in most of the urban
      areas in Pakistan. It is assumed even more perilous than air and water pollution
      due to its direct acute and chronic physio-psychological effects. The objective
      of this study is to analyze and evaluate the psychological and physiological
      effects caused by traffic noise on traffic wardens and to find relation type
      between exposure time and effect. METHODS: Three wardens check posts near roads
      were selected for survey in Taxila and Islamabad cities of Pakistan. Survey
      conducted included noise measurements at aforementioned check posts for one month
      and Performa based interviews of traffic wardens. RESULTS AND CONCLUSIONS:
      Analysis of results showed that noise levels varied between 85-106 dB hence
      violating OSHA regulations. Major psychological effects found in wardens were
      aggravated depression 58%, stress 65%, public conflict 71%, irritation and
      annoyance 54%, behavioral affects 59% and speech interference 56%. Physiological
      effects found were hypertension 87%, muscle tension 64%, exhaustion 48%, low
      performance levels 55%, concentration loss 93%, hearing impairment 69%, headache
      74% and cardiovascular issue 71%. Relation between exposure time and effects were
      evaluated by using simple regression test in excel. Percentage of psychological
      and physiological effects in wardens varied with the exposure time; aggravated
      depression (R(2) = 0.946, P = 0.133), stress suffering (R(2) = 0.014, P = 0.173),
      public conflict (R(2) = 0.946, P = 0.133), irritation and annoyance (R(2) =
      0.371, P = 0.137), behavioral affects (R(2) = 0.596, P = 0.0616) and speech
      interference (R(2) = 0.355, P = 0.445), hypertension (R(2) = 0.96, P = 0.00095)
      and cardiovascular issue (R(2) = 0.775, P = 0.044).

PMID- 25988001
TI  - Malnutrition and infant and young child feeding in informal settlements in
      Mumbai, India: findings from a census.
AB  - Childhood malnutrition remains common in India. We visited families in 40 urban
      informal settlement areas in Mumbai to document stunting, wasting, and overweight
      in children under five, and to examine infant and young child feeding (IYCF) in
      children under 2 years. We administered questions on eight core WHO IYCF
      indicators and on sugary and savory snack foods, and measured weight and height
      of children under five. Stunting was seen in 45% of 7450 children, rising from
      15% in the first year to 56% in the fifth. About 16% of children were wasted and
      4% overweight. 46% of infants were breastfed within the first hour, 63% were
      described as exclusively breastfed under 6 months, and breastfeeding continued
      for 12 months in 74%. The indicator for introduction of solids was met for 41% of
      infants. Only 13% of children satisfied the indicator for minimum dietary
      diversity, 43% achieved minimum meal frequency, and 5% had a minimally acceptable
      diet. About 63% of infants had had sugary snacks in the preceding 24 h, rising to
      78% in the second year. Fried and salted snack foods had been eaten by 34% of
      infants and 66% of children under two. Stunting and wasting remain unacceptably
      common in informal settlements in Mumbai, and IYCF appears problematic,
      particularly in terms of dietary diversity. The ubiquity of sugary, fried, and
      salted snack foods is a serious concern: substantial consumption begins in
      infancy and exceeds that of all other food groups except grains, roots, and
      tubers. 

PMID- 25988004
TI  - The impacts of land cover types on urban outdoor thermal environment: the case of
      Beijing, China.
AB  - BACKGROUND: This study investigated the microclimatic behavior of different land
      cover types in urban parks and, the correlation between air temperature and land
      cover composition to understand how land cover affects outdoor thermal
      environment during hot summer. METHODS: To address this issue, air temperatures
      were measured on four different land cover types at four observation sites inside
      an urban park in Beijing, China, meanwhile, the land cover composition of each
      site was quantified with CAD, by drawing corresponding areas on the aerial
      photographs. RESULTS: The results showed that the average air temperature
      difference among four land cover types was large during the day and small during
      the night. At noon, the average air temperature differed significantly among four
      land cover types, whereas on night, there was no significant difference among
      different land cover types. Results of the linear regression indicated that
      during daytime, there was a strong negative correlation between air temperature
      and percent tree cover; while at nighttime, a significant negative correlation
      was observed between air temperature and percent lawn cover. It was shown that as
      the percent tree cover increased by 10 %, the air temperature decreased by 0.26 
      degrees C during daytime, while as the percent lawn cover increased by 10 %, the
      air temperature decreased by 0.56  degrees C during nighttime. CONCLUSIONS:
      Results of this study help to clarify the effects of land cover on urban outdoor
      thermal environment, and can provide assistance to urban planner and designer for
      improving green space planning and design in the future.

PMID- 25988005
TI  - Assessment of different organic supplements for degradation of Parthenium
      hysterophorus by vermitechnology.
AB  - Globally, there are a number of treatments indicated for the control of invasive
      alien plant species like parthenium. The production and use of vermicomposts from
      weeds or other wastes in agriculture is economical and eco-friendly. The unique
      advantage of using vermicomposting is that it helps to build and sustain soil
      condition and fertility for sustainable agricultural activities. The present
      study was an attempt to produce the vermicompost from Parthenium, farm and animal
      wastes and to analyze its nutrient content and suitability to be used as manure.
      The raw materials Parthenium, farm and animal wastes were collected and
      decomposed by tank method using Eisenia foetida. There were four different
      treatments in three replications of parthenium mixed with farm wastes and animal
      manures @10:1:1 ratio. The pH, organic carbon, organic matter, macro and micro
      nutrients and exchangeable bases were analyzed by standard methods. Addition of
      different farm and animal wastes helped to degrade the Parthenium and improve the
      nutrient value. Different treatments have shown improvements in the degraded
      product in terms of pH, organic carbon, organic matter, macro and micro nutrients
      and exchangeable bases. The vermicompost was found to have a good quality
      comparable to any organic manure. The results revealed the economic feasibility
      of the vermicompost (the organic manure) production as it uses the locally
      available materials and eco friendly nature of its technology. This methodology
      can be adopted by farmers to improve the crop productivity and maintain the soil
      fertility using the locally available organic waste materials. 

PMID- 25988006
TI  - Recurrence of herpes simplex encephalitis associated with temozolomide
      chemoradiation for malignant glioma: a case report and review of the literature.
AB  - Although herpes simplex encephalitis is not classically considered an
      opportunistic infection, reactivation of herpes simplex is being seen
      increasingly in patients with cancer or immunosuppression. The authors present a
      patient with malignant glioma and HSV-1 encephalitis whose PCR-proven
      encephalitis recurred after temozolomide (TMZ) chemoradiation despite acyclovir
      therapy, and summarize details of four other cases of HSV-1 encephalitis
      associated with TMZ. The similarity among these cases raises the likely need for
      longer treatment courses and/or oral suppressive therapy in patients at risk for
      herpes simplex infections who are receiving TMZ. 

PMID- 25988007
TI  - Addison's disease masking a potentially life-threatening condition.
AB  - Addison's disease (AD) is a metabolic disorder that affects the metabolism of
      potassium. The hyperkalemia that results from this condition can be reflected in
      the electrocardiogram, which could confound the diagnosis of other cardiac
      conditions. Such a challenging situation was encountered when a 73-year-old male
      with history of AD presented to the emergency department with chest pain. 

PMID- 25988008
TI  - Possible effects of pramipexole on neck muscles in a patient with Parkinson's
      disease.
AB  - Recent case reports suggest a possible causal correlation between antecollis and
      pramipexole. Here, we report the case of a 62-year-old Italian man with a 2-year
      history of Parkinson's disease (PD) and cervical spondylosis for which he was
      treated with pramipexole. He developed severe neck rigidity immediately after an
      inguinal hernia operation but several months after introduction of pramipexole.
      He was initially treated with painkillers and physiotherapy with no significant
      improvement. His condition deteriorated presenting disproportionate rigidity
      between anterior and posterior neck muscles (antecollis) to the extent that
      normal activities were severely restricted. However, significant improvement
      occurred after the withdrawal of pramipexole. The patient undertook a second
      cycle of physiotherapy with remarkable results and returned to function normally
      in everyday life. This case report suggests that neurologists should be motivated
      to inform the scientific community about other possible cases in which an
      association between antecollis and pramipexole might operate in PD. 

PMID- 25988009
TI  - Acute interstitial lung disease in a patient with anaplastic lymphoma kinase
      positive non-small-cell lung cancer after crizotinib therapy.
AB  - Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma
      kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK
      positive non-small-cell lung cancer (NSCLC). Most drug-related adverse events are
      mild to moderate; however, some patients may develop acute interstitial lung
      disease (ILD) which is sometimes fatal. We present a case of crizotinib
      associated ILD in a 47-year-old woman treated with crizotinib for metastatic
      adenocarcinoma of the lung. The patient presented with acute breathlessness and
      hypoxaemia in the second month of crizotinib therapy; radiological and
      histopathological work-up was suggestive of acute interstitial pneumonia. The
      patient improved clinically with corticosteroid therapy and was successfully re
      challenged with crizotinib. In conclusion, while treating NSCLC patients with
      crizotinib, it is important to promptly investigate and treat any new-onset
      respiratory symptoms, as the latter could represent an adverse effect related to
      therapy. Prompt discontinuation of the offending drug and initiation of
      corticosteroid therapy may prevent adverse outcomes. 

PMID- 25988010
TI  - Moyamoya disease in a patient with neuromyelitis optica.
AB  - Moyamoya disease can be associated with autoimmune disease such as
      thyrotoxicosis, but there has been only one report of association with
      neuromyelitis optica (NMO). We report another case of this combination with the
      presence of anti-SSA antibody in addition to the NMO-immunoglobulin G. The
      patient presented limb weakness along with unsteady gait and numbness. A magnetic
      resonance imaging (MRI) of the spine showed extensive intramedullary hyperintense
      signals at C2 to T3 levels. On the other hand, no lesions were found on the MRI
      of the brain. The patient tested positive for anti-aquaporin-4 antibody and anti
      SSA antibody which confirms the diagnosis of NMO. A magnetic resonance
      angiography scan of the brain revealed a bilateral distal occlusion of the
      internal carotid arteries (ICAs) as well as occlusions of the middle cerebral
      arteries (MCAs) with fine collaterals in the region which confirms the diagnosis
      of moyamoya disease. This report suggests that autoimmunity may be an important
      factor in the pathogenesis of moyamoya disease in some patients. 

PMID- 25988011
TI  - Wilson's disease: 'face of giant panda' and 'trident' signs together.
AB  - Wilson's disease is an inborn error of metabolism characterized by inability to
      excrete copper into the bile, with excessive deposition of copper into the eyes,
      liver and brain. Lentiform nuclei are involved most commonly, but involvement of
      thalamus, midbrain and pons results in certain characteristic radiological signs
      on neuroimaging. Atrophy of cerebral and cerebellar cortex is also common yet
      under-recognized. Identification of these signs helps in the diagnosis in
      appropriate clinical setting. 

PMID- 25988012
TI  - Recurrent spontaneous pneumomediastinum in a young female: Hamman's crunch
      revisited(?).
AB  - Presence of free air in the mediastinum without any identifiable cause is defined
      as spontaneous pneumomediastinum (SPM). SPM is more common in young males. The
      common inciting event leading to SPM are retching, vomiting, acute asthma attack,
      intense sport activity, inhalation of drugs and weight loss as seen in anorexia
      nervosa. Analgesics and rest is the mainstay of treatment. Recurrence of SPM is
      rare. We present a case of recurrent SPM occurring in a young female within few
      months interval. We also present a brief literature review. 

PMID- 25988013
TI  - Multiple cranial neuropathies in cerebral venous sinus thrombosis.
AB  - Clinical presentation of cerebral venous sinus thrombosis (CVST) is varied and
      often mimics many neurological disorders, making it a diagnostic challenge, and
      cranial nerve palsy in CVST is rare and its pathophysiology remains unclear. We
      report a case of a 19-year-old male with a history of whiplash injury, admitted
      with extensive CVST, developed right facial nerve palsy with extension of
      thrombus into the ipsilateral transverse sinus, sigmoid sinus and internal
      jugular vein. Later, he developed left facial nerve palsy with partial left
      occulomotor weakness. We suggest that either reversible compromised oxygen or
      glucose consumption within the intrinsic vascular system of the nerve, resulting
      in cranial nerve abnormalities. CVST should be considered in cases of trivial
      trauma, even in the absence of hyper-coagulable states, and it can have atypical
      presentation like multiple cranial neuropathies. 

PMID- 25988014
TI  - Truth is a daughter of time: a case of MELAS diagnosed 25 years after initial
      manifestation.
AB  - The acronym MELAS (mitochondrial encephalopathy with lactic acidosis and stroke
      like episodes) belies the true scope of one of the most prevalent
      mitochondriopathies in adults. While the original description focused on
      neuromuscular symptoms, we now recognize this syndrome as genetically well
      defined but phenotypically profoundly heterogeneous, as exemplified by our
      experience. Here we report the case of a man who initially presented in 1986. In
      hindsight, his was a classic manifestation of MELAS, but the illness was ascribed
      to an ill-defined viral encephalitis. Over the years, diabetes and hearing
      impairment developed and his functional status deteriorated progressively. It
      took the quarter of a century to arrive at the correct diagnosis. It is
      worthwhile to keep an open mind when dealing with chronically ill patients with a
      seemingly clear-cut diagnosis. 

PMID- 25988015
TI  - Unexplained acute coronary occlusion causing anterior myocardial infarction.
AB  - We present a diagnostic conundrum with a case of a young woman presenting with an
      acute myocardial infarction in cardiogenic shock who was found to have an
      occluded left main stem (LMS). Despite ballooning the LMS, multiple re-occlusions
      in the same area warranted stent deployment. There was a filling defect in the
      left aortic sinus which was evaluated further with a CT scan and transoesophageal
      echocardiogram, confirming a mass consistent with a papillary fibroelastoma. The
      patient went on to have an left ventricular assist device and died while awaiting
      a heart transplant, but the mass was never found at surgery. 

PMID- 25988016
TI  - A case of cough variant asthma undiagnosed for 16 years.
AB  - A 64-year-old female patient presented with a 16-year history of persistent dry
      cough that was undiagnosed after workups at several healthcare facilities. The
      patient denies wheezing, shortness of breath or sputum production. Previous
      workups include chest imaging, transthoracic echocardiogram (TTE), laryngoscopy,
      spirometry and bronchoscopy, all of which were unremarkable. During her current
      evaluation, spirometry was ordered again for the patient, which showed a post
      bronchodilator improvement in the FEV1 by 13%, strongly suggestive of asthma. The
      patient was started on pharmacological therapy for severe persistent asthma,
      which led to sustained symptomatic improvement per evaluation at follow-up after
      2 months. Spirometric findings, clinical presentation and resolution of symptoms
      with adequate therapy for asthma suggest that this is a case of cough variant
      asthma that went undiagnosed for several years. This case report summarizes the
      workup for chronic cough and how the diagnosis of cough variant asthma can be
      missed. 

PMID- 25988017
TI  - Pulmonary renal syndrome: peripheral lung sparing.

PMID- 25988018
TI  - Diaphragm perforation after radiofrequency ablation for liver malignancy.

PMID- 25988019
TI  - Ictal bradycardia and atrioventricular block: a cardiac manifestation of
      epilepsy.
AB  - We describe a case of a patient with recurrent syncopal episodes that ultimately
      was discovered to be due to ictal bradycardia caused by temporal lobe epilepsy. A
      diagnostic dilemma was presented by a 55-year-old male who had recurrent syncopal
      events despite having an atrial pacemaker. The patient was noted to have
      automatisms and was diagnosed via electrocardiogram/electroencephalogram
      (EEG/ECG) co-registration to have ictal bradycardia and atrioventricular (AV)
      block leading to syncope. He was successfully managed with seizure control with
      the use of levetiracetam. Ictal bradycardia and AV block are uncommon
      manifestations of epilepsy and can progress to complete heart block and asystole.
      Diagnosis is best performed with simultaneous ECG and EEG recordings. Definitive
      management is seizure control with the use of antiepileptic drugs, with the
      question of pacemaker placement still up for debate. 

PMID- 25988020
TI  - Nocardia farcinica complicating Cogan's syndrome.
AB  - Nocardiosis is an uncommon bacterial gram-positive infection caused by aerobic
      actinomycetes in the genus Nocardia. Nocardiosis is typically regarded as an
      opportunistic infection with approximately two-thirds of infected patients being
      immunocompromised. In this case report we describe a 45-year-old female who
      presented with a right thigh abscess. She had been taking high-dose prednisolone
      and ciclosporin for Cogan's syndrome. She presented with erythema and severe pain
      over her right thigh. Ultrasound showed a collection and Nocardia farcinica was
      isolated. This case report stresses the importance of considering atypical
      infections in immunocompromised patients, even with minor symptoms, to avoid
      delay in diagnosis and treatment. 

PMID- 25988021
TI  - Editorial.

PMID- 25988022
TI  - Meningitis complicated by mycotic aneurysms.
AB  - Mycotic aneurysms complicated by vasospasm and strokes represent a rare
      manifestation of bacterial meningitis. We describe a healthy woman diagnosed with
      bacterial meningitis and mycotic aneurysms, who received both antibiotic and
      corticosteroid therapy. This approach fostered a significant radiologic
      improvement in her mycotic aneurysms as evidenced by serial angiographic
      examinations. During her course, she developed vasospasm and strokes and required
      intra-arterial verapamil. More importantly and as a result of these combined
      therapies, the patient experienced a substantial clinical improvement. This case
      allows the description of mycotic aneurysms epidemiology, clinical presentation
      and complications. In addition, our vignette bestows the relevance of serial
      neurologic examinations and radiologic testing during the acute vasculopathy
      period. Current conservative and interventional therapeutic options are briefly
      discussed. 

PMID- 25988023
TI  - Cat scratch disease in Medellin, Colombia.
AB  - Cat scratch disease (CSD) is the most common zoonosis transmitted by household
      animals. There is limited data on the epidemiology and clinical presentation of
      this disease in Colombia. The typical presentation includes subacute or chronic
      lymph node infection following inoculation of Bartonella henselae bacilli through
      a cat scratch. Cats have a B. henselae seroprevalence as high as 90%. Here, we
      report the case of a preschool boy from a rural area of Antioquia, Colombia, who
      presented with chronic lymphadenopathy in the right axilla. Other important
      infectious etiologies were ruled out, and confirmation was made with the Warthin
      Starry stain of a lymph node biopsy. We also discuss the most important aspects
      of the diagnosis, treatment and prevention of the disease. 

PMID- 25988024
TI  - Dual left anterior descending coronary artery (type IV): a rare coronary artery
      anomaly.
AB  - The variants of the left anterior descending (LAD) coronary artery are important
      in interpretation of coronary angiogram and in interventional procedures. The
      double LAD coronary artery originating from the left main coronary stem and the
      right coronary artery is a rare congenital coronary anomaly. In this case report,
      we are describing a patient with the double left anterior descending coronary
      artery (type IV), one with normal origin, and the other originating from the
      right coronary artery. Anatomical knowledge of this rare variant of LAD is
      important for novice interventional cardiologists during interpretation of
      coronary angiogram. To the best of our knowledge, there are ~28 cases of dual LAD
      (including type IV) reported in the literature. 

PMID- 25988025
TI  - Desmoplastic malignant mesothelioma of the peritoneum.
AB  - Malignant mesothelioma is an uncommon neoplasm arising in body cavities lined by
      the mesothelium. Immunohistochemical stains are useful for making a diagnosis,
      but the correct combination of antibodies as should be selected in a
      comprehensive assessment. A peritoneal origin combined with desmoplastic
      histology is an extremely rare disease entity. Here, we report a case of the
      primary peritoneal malignant mesothelioma. A 53-year-old man admitted to the
      hospital with abdominal distension and pelvic pain. In laparotomy, peritonitis
      carcinomatosa situation was exposed. Multiple biopsies were taken from omentum,
      peritoneum and fascia. Calretinin, WT-1, D2-40, keratin 5/6, mesothelin, keratin
      7, keratin 20, CD99, CEA, smooth muscle actin, desmin, CD34 and S-100 were
      negative. With these findings tumor was evaluated as desmoplastic malignant
      mesothelioma of the peritoneum. Currently, no established standard treatments for
      malignant peritoneal mesothelioma, but early diagnosis by exploratory laparotomy
      followed by chemotherapy may have contributed to longer survival for patients. 

PMID- 25988026
TI  - Pregnancy delusion hinders the diagnosis of achalasia in a patient with life
      threatening emaciation.
AB  - Abnormal eating behaviour among psychiatric patients is associated with several
      psychiatric conditions, but may also be caused by a comorbid physical condition.
      Clinical assessment of a psychiatric patient is often challenging, which
      contributes to an increased rate of undiagnosed medical conditions and an
      increased mortality rate. We present the clinical case of a 46-year-old woman
      with a long-term delusion of triplet pregnancy, and recurrent vomiting. She
      experienced intense weight loss and eventually faced a life-threatening situation
      due to achalasia, which was incidentally discovered on a chest X-ray during her
      second psychiatric hospitalization, after several other tests, including upper
      digestive endoscopy, returned normal results. After a successful laparoscopic
      Heller's myotomy, her digestive symptoms greatly improved. This report
      illustrates the difficulty of establishing clinical-surgical diagnoses in
      psychotic patients, as some delusions seem to explain clinical complaints,
      masking and delaying the diagnosis of comorbid conditions. 

PMID- 25988027
TI  - Giant spider angiomas.

PMID- 25988029
TI  - Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic
      dilemma.
AB  - Post-operative cognitive dysfunction (POCD) is common in the elderly, and
      significantly impacts their recovery. We present an unusual diagnostic challenge
      where a 65-year-old male presented 4-week post-total knee arthroplasty with acute
      cognitive dysfunction lasting 19 days. Curiously, there were no findings
      uncovering a specific cause, but during investigation underlying predisposing
      factors such as depression, mild memory deficits and generalized brain volume
      loss were identified. The impression after psychogeriatric review was that of an
      organic brain syndrome with overlay of depression, with a complex presentation as
      POCD. After escalation of behavioural disturbance, he was commenced on anti
      psychotic/depressant, with immediate response. We emphasize the importance of pre
      operative evaluation of cognitive function and risk factors in all geriatric
      patients undergoing elective surgery, and the need for further characterization
      of POCD, as well as experimental research elucidating the underlying mechanisms
      to better identify and treat this important post-surgical phenomenon. 

PMID- 25988028
TI  - Meningeal haemorrhage secondary to cerebrospinal fluid drainage during thoracic
      endovascular aortic repair.
AB  - Thoracic endovascular aortic repair (TEVAR) has shown lower mortality compared
      with open surgical repair (OSR). However, the risk of spinal cord ischaemia (SCI)
      remains similar than OSR. As a prophylactic measure to reduce the risk of SCI,
      cerebrospinal fluid (CSF) drainage has been widely used in OSR. In TEVAR, the
      utility of this adjunct is still controversial. We report a case of a 56-year-old
      man referred for TEVAR for a descending thoracic aneurysm that previously
      underwent an abdominal aneurysmectomy with aortobifemoral bypass graft. On the
      day before, a lumbar cerebrospinal drain was placed prophylactically. Forty-eight
      hours after the procedure, meningeal symptoms without neurological deficits
      developed. Clinical investigation revealed meningeal haemorrhage. Therapy with
      nimodipine was initiated with symptomatic relief. Evidence from randomized
      controlled trials supporting the role of CSF drainage in TEVAR is still lacking.
      We discuss the current recommendations, potential benefits and risks and cautions
      associated with CSF drainage in TEVAR. 

PMID- 25988030
TI  - Development and remission of depressive symptoms and treatment with hormonal
      contraceptives.
AB  - We present two cases of female patients with a history of depression who
      developed depressive symptoms after treatment with hormonal contraceptives (HC)
      in the form of combined oral contraceptive pill, progestin-only pill and combined
      contraceptive vaginal ring. The presented two cases are based on the women's
      medical records complemented by personal interviews. The existing literature on
      the effects of HC on depression is inconclusive. Patient-based decisions with
      consideration of the individual history and predispositions are recommended when
      starting oral contraceptives. If depressive symptoms occur, decisions regarding
      discontinuation need to be made on an individual basis. 

PMID- 25988031
TI  - Acute response and chronic stimulus for cardiac structural and functional
      adaptation in a professional boxer.
AB  - The individual response to acute and chronic changes in cardiac structure and
      function to intense exercise training is not fully understood and therefore
      evidence in this setting may help to improve the timing and interpretation of pre
      participation cardiac screening. The following case report highlights an acute
      increase in right ventricular (RV) size and a reduction in left ventricular (LV)
      basal radial function with concomitant increase at the mid-level in response to a
      week's increase in training volume in a professional boxer. These adaptations
      settle by the second week; however, chronic physiological adaptation occurs over
      a 12-week period. Electrocardiographic findings demonstrate an acute lateral T
      wave inversion at 1 week, which revert to baseline for the duration of training.
      It appears that a change in training intensity and volume generates an acute
      response within the RV that acts as a stimulus for chronic adaptation in this
      professional boxer. 

PMID- 25988032
TI  - Acute hyperammonaemic encephalopathy.

PMID- 25988033
TI  - A salty cause of cough in a 24-year-old man.
AB  - With improvement in the diagnosis and treatment of cystic fibrosis cases in
      recent years, the survival of these cases has been increased. On the other hand,
      an increasing number of cases are presented during adulthood. Here we report a 24
      year-old man with a history of productive cough, bilateral paranasal sinusitis
      and polyps, and recurrent abdominal pain. Thoracic computed tomography revealed a
      bilateral scattered tree in bud pattern and some bronchiectatic changes. Semen
      analysis showed azoospermia. A sweat chloride test was >60 mEq/l in two
      occasions. 

PMID- 25988034
TI  - Cognitive dysfunction during anti-NMDA-receptor encephalitis is present in early
      phase of the disease.
AB  - Anti-NMDA-receptor encephalitis is an autoimmune disorder with a well-defined set
      of clinical features including psychiatric changes (anxiety, agitation, bizarre
      behaviour, delusional or paranoid thoughts), epileptic seizures and cognitive
      disturbance followed by movement disorders including orofacial dyskinesias,
      alterations in the level of consciousness and dysautonomia. Although the
      cognitive changes are not always very clear at presentation, they can persist
      after recovery from the acute and often prolonged illness. However, there are few
      studies describing neuropsychiatric changes in depth, both in the early course of
      the disease and in long-term follow-up. 

PMID- 25988035
TI  - Primary hypoparathyroidism presenting with heart failure and ventricular
      fibrillation.
AB  - A 24-year-old female presented with sudden heart failure and ventricular
      fibrillation. A complete work-up suggested the existence of primary
      hypoparathyroidism in an otherwise previously healthy young woman. Left ventricle
      enlargement was detected by echocardiography with an ejection fraction of 30%.
      Electrolyte disorders dominated the laboratory results, with severe hypocalcemia,
      hypokalemia, hypomagnesemia and other changes, which were corrected with infusion
      therapy. An improvement of her overall condition prompted a switch from
      electrolyte infusion therapy to the oral route after the first week of treatment.
      The patient was discharged under calcium, calcitriol, diuretics and angiotensin
      converting-enzyme-inhibitors oral maintenance therapy. Two months after
      discharge, her ejection fraction remained low (33%), although the end-systolic
      volume had returned to normal values, and her general status had substantially
      improved. Within a period of 4 months her cardiac function improved significantly
      and the follow-up surveillance echocardiography showed an ejection fraction of
      53%, with normal left ventricle dimensions. 

PMID- 25988036
TI  - Recurrent gastric lactobezoar in an infant.
AB  - Lactobezoars are a type of bezoar composed of undigested milk and mucus. The
      aetiology is likely multifactorial, being classically described in association
      with pre-term, low-birth weight infants fed with hyperconcentrated formula. The
      authors present a case of lactobezoar recurrence in a pre-term infant with
      oesophageal atresia. To our knowledge, this is the first report of recurrence of
      lactobezoar. 

PMID- 25988037
TI  - Pulmonary strongyloidiasis following renal transplantation without travel to an
      endemic area.
AB  - We report a case of Strongyloides stercoralis hyperinfection in an
      immunosuppressed individual occurring in a non-endemic area. Geographic risk is
      not sufficient to rule out Strongyloidiasis in susceptible individuals presenting
      with severe pulmonary disease. 

PMID- 25988038
TI  - Sarcoidosis presenting with hypercalcaemia following withdrawal of long-term
      immunosuppression in renal transplantation.
AB  - Long-term immunosuppression, including corticosteroids, is a hallmark of renal
      transplantation. We describe a patient who had a failed transplant after 15
      years, subsequent graft nephrectomy and withdrawal of his immunosuppression
      therapy including prednisolone. Within months of complete cessation of
      prednisolone, he developed hypercalcaemia and subsequent systemic symptoms
      including ocular, respiratory and dermatological. A skin biopsy demonstrated non
      caseating granulomatous lesion and a diagnosis of sarcoidosis was confirmed. Re
      commencement with prednisolone resulted in complete resolution of clinical and
      biochemical features of sarcoidosis. Sarcoidosis is unlikely to present in the
      immunosuppressed patient. This case highlights that unexplained hypercalcaemia at
      the time of withdrawal of immunosuppression, including corticosteroids, may be a
      feature of sarcoidosis. 

PMID- 25988039
TI  - Colonic perforation following endoscopy revealed by plain radiography.

PMID- 25988040
TI  - Acute adrenal insufficiency as a first presentation of myelodysplastic syndrome
      and sigmoid colon adenocarcinoma: a case report.
AB  - Acute adrenal failure due to bilateral adrenal haemorrhage is rare and may
      initially present with non-specific symptoms. It can rapidly progress into a life
      threatening condition if not diagnosed promptly. Both traumatic and non-traumatic
      conditions have been implicated in the aetiology, with the latter been even
      rarer. We describe the case of a 57-year-old woman presenting with vomiting and
      epigastric pain and later developing fever and diarrhoea. The patient then
      deteriorated into shock and primary adrenal insufficiency was identified. A
      computed tomography scan noted bilateral adrenal haemorrhage. Further
      investigations showed a sigmoid colon adenocarcinoma and a myelodysplastic
      syndrome, with monosomy seven. Bilateral non-traumatic adrenal haemorrhage is an
      infrequent finding and investigating its aetiology can be challenging. In our
      patient, two simultaneous underlying diseases were identified. To the best of our
      knowledge, the combination of these two non-traumatic conditions as a cause of
      acute bilateral adrenal haemorrhage has not been previously reported. 

PMID- 25988041
TI  - A case of thoracic splenosis in a post-splenectomy patient following abdominal
      trauma: Hello Howell-Jolly.
AB  - Seeding of splenic tissue to extra-abdominal sites is a relatively infrequent
      consequence of open abdominal trauma. Immunological function of these small foci
      of ectopic splenic tissue is unknown and their use in determining the splenic
      function may be limited. In this case report, a patient is described who had
      previously undergone an emergency splenectomy. The absence of Howell-Jolly bodies
      on the blood smear in a patient who had previously undergone surgical splenectomy
      raised the suspicion of splenosis. The immunological features as well as non
      invasive evaluation of these ill-defined splenic tissue sites are discussed. 

PMID- 25988042
TI  - Incidentalomas to glioblastoma multiforme.
AB  - In April 1999, a 25-year-old male underwent magnetic resonance imaging (MRI) as a
      control subject for a multiple sclerosis study. The scan serendipitously revealed
      two lesions ('incidentalomas') in the right frontal lobe. Initially, he was
      asymptomatic and was monitored with interval MRI scans. After years of
      monitoring, contact was accidentally lost. He later presented following a
      witnessed generalized seizure. He was commenced on phenytoin, which was changed
      to carbamazepine due to side effects. MRI revealed three gliomas and an open
      brain biopsy confirmed a diagnosis of low-grade astrocytoma. The location and
      multifocal nature of the gliomas ruled out complete neurosurgical debulking.
      However, his seizures increased in frequency and in February 2007, the biopsy
      confirmed malignant transformation to multifocal glioblastoma multiforme. He
      successfully underwent partial debulking, radiotherapy and adjuvant temozolomide
      chemotherapy. Currently, he is 6 years post-treatment and asymptomatic. 

PMID- 25988043
TI  - Epidermal growth factor receptor inhibitors related trichomegaly of Eyelashes.
AB  - Advances in understanding of the mechanisms involved in oncogenesis have led to
      the development of targeted therapies such as epidermal growth factor receptor
      inhibitors (EGFRIs), targeting a variety of molecular structures and able to
      inhibit aberrantly activated oncogenic pathways. Their use made treatment more
      tolerable with significant reduction of systemic adverse effects. However, EGFRIs
      are associated with toxicities affecting the skin and adnexal structures that
      affect the majority of treated patients. Trichomegaly of eyelashes is a unique
      side-effect, seen in prolonged treatment with EGFRI. It is essential to be
      familiar with this adverse effect, its potential complications, long-term
      sequelae, and available effective treatment strategy in order to appropriately
      manage these patients. 

PMID- 25988044
TI  - It is never too late to treat anxiety neurosis or panic disorder with a serotonin
      reuptake inhibitor.
AB  - In a register study on patients hospitalized in the 1950s for anxiety neurosis,
      going until 1994 for diagnostic behaviour and until 2004 for suicidal behaviour,
      we found a co-existence with depression. However, the study has no information
      about therapy. Just after the finalization of this study, one of the patients was
      hospitalized in our department for depression. At that time the patient was 70
      years old; at his index hospitalization in 1954 he was 30 years of age.
      Throughout his 40 years of illness he had received no psychiatric treatment. The
      spontaneous course went from panic attacks through stages of phobia and avoidance
      behaviour until the final stage of depression. At 70 years of age, for the first
      time in his life, he received antidepressant medication in the form of a specific
      serotonin re-uptake inhibitor. After 6 weeks of therapy not only the depression
      but also the anxiety disorder remitted. 

PMID- 25988045
TI  - LMNA-related dilated cardiomyopathy.
AB  - A case of idiopathic dilated cardiomyopathy (DCM) that is likely to be associated
      with LMNA mutation Arg190Pro in a heterozygote is described. The features of DCM
      in the patient were conduction disorders, cardiac arrhythmias, progressive heart
      failure and minor musculoskeletal disturbances. We consider that the mutation
      Arg190Pro contributes to the formation of a weak nuclear lamina and diminishes
      muscle mechanical stability which is critical during cardiac contraction. The
      case report illustrates in detail the phenotypic manifestations of the novel LMNA
      mutation and difficulties in management related to it. 

PMID- 25988046
TI  - Enduring complete metabolic response in metastatic adenocarcinoma of the gastro
      oesophageal junction.
AB  - We report on a 46-year-old gentleman who presented with a poorly differentiated
      invasive adenocarcinoma of the gastro-oesophageal junction, local lymph node
      involvement and bilobar liver metastases. Nearly 2 years after diagnosis, he has
      sustained complete metabolic response and remains in excellent clinical condition
      after treatment with chemoradiotherapy. Fluorodeoxyglucose positron emission
      tomography images at diagnosis and after treatment have been provided. 

PMID- 25988047
TI  - Disseminated tuberculosis causing isolated splenic vein thrombosis and multiple
      splenic abscesses.
AB  - Tuberculosis is a common infectious cause of splenic enlargement in developing
      countries, but tubercular splenic abscesses are a rare presentation, found
      predominantly in immunocompromised populations. We report a case of tubercular
      splenic abscesses with isolated splenic vein thrombosis in an immunocompetent
      person. 

PMID- 25988048
TI  - Visceral leishmaniasis with Roth spots.
AB  - Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania
      donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes.
      The protozoa is obliged intracellularly and causes a wide spectrum of clinical
      syndromes: VL ('kala azar'), cutaneous leishmaniasis and mucocutaneous
      leishmaniasis (espundia). Kala azar is the most aggressive form and if untreated
      causes high mortality. Here, we describe a case of VL that presented to us with
      high-grade fever and found to have Roth spots that were resolved after 15 days of
      therapy. 

PMID- 25988049
TI  - Sneathia species in a case of neonatal meningitis from Northeast India.
AB  - Here we report the detection of Sneathia species most closely related to Sneathia
      sanguinegens, an infrequently reported bacterium, in the cerebrospinal fluid of a
      neonate by a culture independent method. Even though on rare occasions, this
      bacterium was isolated previously from the blood of neonatal bacteraemia cases.
      To the best of our knowledge there exists no previous report of detection of S.
      sanguinegens in the cerebrospinal fluid even though recently there has been a
      report of isolation of closely related species, Leptotrichia amnionii. The
      neonate recovered following antimicrobial therapy for 21 days. We conclude that
      uncultivable or difficult- to-cultivate bacteria like Sneathia could be an
      emerging pathogen for neonatal infection. 

PMID- 25988050
TI  - An unexpected cause of orbital apex syndrome in an immune-competent elderly male.
AB  - Invasive aspergillosis causing orbital apex syndrome (OAS) in an immune-competent
      individual is a very rare phenomenon, scarcely reported in medical literature. A
      68-year-old male presented with progressive loss of vision in the right eye,
      starting after a cataract surgery. Neurological examination suggested OAS.
      Imaging was suggestive of mass lesion causing destruction of ethmoid bone. Biopsy
      of the lesion could not be done initially in view of its proximity to the major
      neuro-vascular bundle in the orbital apex and cavernous sinus and the major risk
      involved in the procedure relative to its yield. There was no response to
      empirical therapy with antibacterials, steroids or Amphotericin-B. Gradually the
      mass increased in size and was amenable to biopsy. Endoscopy guided biopsy
      revealed invasive aspergillosis. Switching over to voriconazole lead to
      successful management. This case highlights the importance of early diagnosis and
      selection of an appropriate antifungal therapy in the management of invasive
      aspergillosis. 

PMID- 25988051
TI  - Co-infection of Sarcina and Giardia in a child.
AB  - We present a case of 3-year-old boy who presented with vomiting and chronic
      diarrhoea, and the duodenal biopsy showed the presence of both Giardia and
      Sarcina. The clinical and pathological significance of Sarcina remains unknown in
      human beings and its co-existence with Giardia has not been reported. 

PMID- 25988052
TI  - Chronic rupture of the coronary sinus of Valsalva with pseudoaneurysm formation.

PMID- 25988054
TI  - Disseminated tuberculosis with tuberculous meningitis in an immunocompetent host.
AB  - Disseminated tuberculosis (TB) results from the lymphohematogenous spread of
      Mycobacterium tuberculosis. Despite the availability of effective therapy,
      diagnosis is usually late and mortality remains high. We report a case of a 29
      year-old male with a history of alcohol abuse that presented with altered mental
      status and was found to have a 'tree-in-bud' sign on chest radiography. Chest
      computed tomography revealed innumerable pulmonary nodules in a miliary pattern.
      Examination of sputum and cerebrospinal fluid was positive for M. tuberculosis on
      nucleic acid amplification testing. The case emphasizes the importance of
      considering disseminated TB in patients with risk factors and typical
      radiographic patterns even in geographic areas with low disease prevalence. 

PMID- 25988053
TI  - Aggressive vertebral hemangioma in the postpartum period: an eye-opener.
AB  - Pregnancy is a well-known risk factor for incidental or asymptomatic vertebral
      hemangiomas becoming aggressive or symptomatic, most often during the third
      trimester of pregnancy, related to hemodynamic and endocrinal changes occurring
      during pregnancy. Many patients show spontaneous incomplete remission after
      delivery. We report a rare case of aggressive vertebral hemangioma in the
      postpartum period in a 26-year-old woman, who presented with upper backache with
      progressive spastic paraparesis. 

PMID- 25988055
TI  - But he has no chest pain....
AB  - Atypical presentations of acute coronary syndromes (ACS) are not uncommon and
      have been associated with higher mortality probably, because these patients are
      misdiagnosed and undertreated. They are most frequently encountered in older
      patients, women and in patients with diabetes, chronic renal failure or dementia.
      It is also well described in the literature that many chemotherapy agents are
      associated with myocardial ischaemic events. In addition to that, patients with
      cancer frequently receive large doses of opiate analgesics for chronic pain,
      which can obscure the symptoms of myocardial ischaemia. In this case report, we
      describe a patient who was receiving chemotherapy and large doses of opiate
      analgesics and presented with atypical symptoms for ACS. Our aim is to raise
      awareness of this challenging group of patients and the necessity to pay
      particular attention to symptoms other than chest pain as potential indicators of
      myocardial ischaemia. 

PMID- 25988056
TI  - Acute aseptic meningitis due to intravenous immunoglobulin therapy in Guillain
      Barre syndrome.
AB  - The majority of adverse reactions of intravenous immunoglobulin (IVIG) therapy
      are mild, transient and self-limiting with potentially serious complications
      occurring in <5% of patients. IVIG-associated transient aseptic meningitis is one
      such rare adverse effect, which has been seldomly described in the literature. We
      report a case of aseptic meningitis due to IVIG therapy in a Guillain-Barre
      syndrome (GBS) patient. The cerebrospinal fluid analysis revealed high cell
      counts with predominance of lymphocytic cells, raised protein, normal glucose
      level and no growth of the organisms on culture. The patient improved with
      supportive care such as intravenous fluids and analgesics without neurological
      complications. This case emphasizes the importance of recognizing IVIG-associated
      complications like aseptic meningitis in GBS patients. 

PMID- 25988057
TI  - Secondary Sjogren's syndrome presenting with hypokalemic periodic paralysis.
AB  - Renal tubular acidosis (RTA) may develop in a large population of patients with
      Sjogren's syndrome (SS), but most of the subjects are asymptomatic. Here, we
      report a patient with known rheumatoid arthritis and symptoms of xerostomia,
      xerophthalmia and periodic paralysis. SS should be considered as a cause of RTA.
      The treatment of the underlying disorder may ameliorate the symptoms. 

PMID- 25988058
TI  - Tumor lysis syndrome and acute anemia in an African-American man with chronic
      lymphocytic leukemia.
AB  - Tumor lysis syndrome (TLS) is a life-threating hematologic emergency caused by
      massive lysis of tumor cells into the blood stream. TLS can be prevented and
      treated with rasburicase. Rasburicase-induced hemolysis and methemoglobinemia is
      a rare but serious complication. Screening for G6PD should be considered for
      patients at higher risk for G6PD deficiency who may be also at high risk for TLS
      on the basis of clinical parameters. G6PD level in G6PD-deficient patients may be
      normal during an acute hemolytic episode and may not help to clarify the
      diagnosis at the time of presentation. The characteristic peripheral blood smear
      findings of 'bite' and 'blister' cells representing oxidative damage to red blood
      cells can help to quickly establish the diagnosis of G6PD deficiency-related
      hemolysis. The treatment of an acute hemolytic episode in a patient with G6PD
      deficiency requires avoiding the source of oxidative stress and using transfusion
      support as needed. 

PMID- 25988059
TI  - A rare case of multifocal lymphadenopathy in a young male.
AB  - Lymphadenopathy can be caused by localized and systemic diseases. While viral and
      bacterial infections commonly cause lymphadenitis in young adults, tuberculosis
      (TB) is a common cause for lymphadenopathy in endemic areas. Besides,
      lymphadenopathy may be a presenting manifestation of malignancy, systemic
      disorders and some rare diseases. Thus, relevant evaluation and exclusion of
      commoner causes is important to clinch the diagnosis. Histopathological
      examination is mandatory in such patients. We hereby report the case of a young
      adult male who presented with low-grade fever and abdominal pain with cervical
      and mesenteric lymphadenopathy in a TB endemic region, but was proved to have
      atypical presentation of Kikuchi-Fujimoto disease, which is a rare but benign
      cause of lymphadenopathy. 

PMID- 25988060
TI  - Polymorphous light eruption: a common skin disease uncommonly recognized in the
      Hispanic population.
AB  - Polymorphous light eruption (PMLE) is a common acquired disease entity belonging
      to the idiopathic photodermatoses that is uncommonly considered in the Hispanic
      population. The pathogenesis of the disease and the mechanism of adaptation in
      skin (hardening phenomenon) have yet to be elucidated. PMLE is characterized by
      recurrent abnormal delayed reactions to sunlight ranging from pruritic
      erythematous papules, papulovesicles and plaques to erythema multiforme. It
      commonly occurs in the spring or early summer with a predilection for females. A
      Pubmed review of the literature shows no case reports or literature regarding
      PMLE in Hispanics. To the best of our knowledge, we report the first case of a 41
      year-old Hispanic female diagnosed with PMLE. A high index of suspicion must
      remain in this group. Additional studies reviewing epidemiology in this group and
      detailing similar cases may be suggested. 

PMID- 25988061
TI  - Primary hepatic tuberculosis in immunocompetent adults: a UK case series.
AB  - Primary hepatic tuberculosis (TB) is very rare in the UK, but the incidence may
      be rising. Three cases of primary hepatic TB in immunocompetent patients without
      evidence of pulmonary involvement are reported. The diagnosis was challenging as
      two patients had liver space-occupying lesions, and the third patient presented
      with liver abscess. All of them responded well to standard anti-tubercular
      treatment. Hepatic TB should be considered in the differential diagnosis of space
      occupying lesions of the liver and liver abscesses. 

PMID- 25988062
TI  - Porphyria and anorexia: cause and effect.
AB  - Porphyrias are hereditary disorders related to impaired biosynthesis of heme and
      characterized by multisystemic manifestations. Acute intermittent porphyria (AIP)
      is the most common acute subtype of the disease, and often associated with
      psychiatric symptoms. We here report a patient who developed acute flaccid
      paralysis after remarkable weight loss, which was related to an eating disorder
      (anorexia nervosa). After an extensive neurologic workup, he was diagnosed with
      AIP. This case emphasizes a deleterious vicious cycle between AIP and anorexia:
      porphyria may lead to anorexia and the carbohydrate restriction may lead to
      recurrent porphyric attacks. Therefore, an interruption of this cycle with
      psychiatric approaches to the eating disorders is crucial for long-term
      therapeutic efficacy. 

PMID- 25988064
TI  - The rising tide of bloodstream infections with Actinomyces species: bimicrobial
      infection with Actinomyces odontolyticus and Escherichia coli in an intravenous
      drug user.
AB  - Clinicians of all specialties need to be aware of a recent, nationwide increase
      in the number of Actinomyces bloodstream infections. We report a case of
      bimicrobial bloodstream infection with Actinomyces odontolyticus and Escherichia
      coli in an intravenous drug user. A 36-year-old, male intravenous drug user was
      admitted with acute-onset pleuritic chest pain, back pain, pyrexia, tachycardia,
      tachypnoea and hypotension. Chest CT showed multiple, bilateral, cavitating lung
      lesions, most likely the result of septic emboli originating from an infected
      deep venous thrombosis (DVT). Blood cultures led to a mixed growth of A.
      odontolyticus, identified by matrix-assisted laser desorption ionization time-of
      flight (MALDI-TOF), and E. coli. The rising tide of bloodstream infections with
      Actinomyces species is likely to continue with the increasing availability of
      sophisticated molecular identification techniques, including MALDI-TOF. In this
      case, the results of antimicrobial susceptibility tests were particularly
      important because the E. coli was susceptible to ciprofloxacin, whereas the A.
      odontolyticus was resistant. 

PMID- 25988063
TI  - Primary hepatic tuberculosis presenting as acute liver failure.
AB  - Abdominal tuberculosis is a common clinical entity in Indian subcontinent;
      however, hepatic tuberculosis in the absence of miliary abdominal tuberculosis is
      restricted to the case reports and small case series in English literature. It
      mimics common liver diseases like liver abscess and tumors. We report a case of
      25-year-old immunocompetent female who presented with features of acute liver
      failure. Ultrasonography (USG) abdomen revealed multiple hypoechoic lesions.
      However, patient expired within 48 h of presentation but her liver autopsy
      revealed multiple epithelioid cell caseating granulomas with positive staining
      for acid fast bacilli (AFB). Polymerase chain reaction (PCR) was also positive
      for Mycobacterium tuberculosis. 

PMID- 25988065
TI  - Plasma cell leukaemia: a management conundrum.
AB  - Primary plasma cell leukaemia in a young transplant eligible patient brings forth
      a number of perplexing questions and many remain unanswered. There are good data
      to suggest the superiority of novel agents over conventional chemotherapy
      regimens, however choosing between autologous and allogeneic haematopoietic stem
      cell transplant in first remission remains a therapeutic conundrum. We report a
      case of primary plasma cell leukaemia in a young patient and the dilemmas in its
      management. 

PMID- 25988066
TI  - Lyme meningo-radiculitis responsive to oral doxycycline therapy in the USA.
AB  - The spirochete strains that cause Lyme disease are different between the USA and
      Europe. This leads not only to a variation in clinical presentations, but it was
      also thought to alter responsiveness to antibiotic treatment. Unlike in Europe,
      in the USA there are no head-to-head trials of oral and intravenous antibiotics
      in the treatment of neuroborreliosis. Guidelines from the American Academy of
      Neurology (AAN) state that oral doxycycline is probably safe and effective in
      treating neuroborrliosis without parenchymal involvement, this was mainly
      extrapolated from European studies data with no reports from North America. To
      the best of our knowledge, this is the first reported case of Lyme meningo
      radiculitis successfully treated with oral doxycycline alone in the USA. This
      comes in support of the oral doxycycline as an initial and even monotherapy for
      non-parenchymal Lyme disease of the nervous system in the USA. 

PMID- 25988067
TI  - VACTERL association-type anomalies in a male neonate with a Y-chromosome
      abnormality.
AB  - The acronym VACTERL describes the non-random co-occurrence of three of the
      following anomalies: vertebral (V), anal (A), cardiac (C), tracheoesophageal
      fistula with or without oesophageal atresia (TE), renal (R) and limb defects (L).
      Here, we report a newborn baby with VACTERL-type anomalies along with a single
      umbilical artery. The additional interesting findings include development
      dysplasia of the right hip, dislocation of the left knee and the left club foot.
      The karyotype revealed 46, X,i (Yp), i.e. deletion in the long arm, while
      duplication in the short arm of the Y chromosome (isochromosome Yp), which has
      never been previously reported in VACTERL association. 

PMID- 25988068
TI  - Eculizumab treatment for paroxysmal nocturnal haemoglobinuria in a patient with
      recurrent simultaneous multivessel coronary stent thrombosis.
AB  - We describe a case of recurrent multivessel coronary stent thrombosis in the
      absence of the typical hallmarks of this phenomenon: (i) discontinuation or poor
      compliance with double antiplatelet therapy; (ii) stent malapposition and (iii)
      stent underexpansion. In this case, the recurrence of stent thrombosis was indeed
      manifestation of a more complex underlying disease, and eventually allowed the
      clinicians to come to the final diagnosis of paroxysmal nocturnal
      haemoglobinuria. 

PMID- 25988069
TI  - Localized malignant pleural mesothelioma with renal metastasis.
AB  - Localized malignant pleural mesothelioma (LMM) is a rare subset of malignant
      pleural mesothelioma. Its epidemiology, biology, natural history and optimal
      treatment are poorly understood. We report a case of LMM treated aggressively
      with complete surgical resection and adjuvant radiotherapy, but subsequently
      complicated by local chest wall recurrence and solitary metastasis to the kidney.
      This case is examined in the context of a small number of cases of LMM in the
      literature to emphasize the existence of this rare disease entity, their unusual
      biological behaviour and the need for further tumour molecular and genomic
      research. 

PMID- 25988070
TI  - Spontaneous coronary artery dissection: a rare diagnosis in a postmenopausal
      woman.
AB  - We report a case of a 50-year-old ex-smoker, postmenopausal woman presenting with
      an acute myocardial infarction caused by a spontaneous coronary artery dissection
      of a long 'wrap-around' left anterior descending coronary artery. After the
      diagnostic coronary angiography, she was treated medically with subsequent
      improvement. 

PMID- 25988071
TI  - 'Tendon xanthomas' as an indicator of premature coronary artery disease.

PMID- 25988072
TI  - Thrombotic thrombocytopenic purpura with concomitant small- and large-vessel
      thrombosis, atypical posterior reversible encephalopathy syndrome and cerebral
      microbleeds.
AB  - We report a case of thrombotic thrombocytopenic purpura (TTP) with uncommon
      imaging features, namely concomitant small- and large-vessel thrombosis, atypical
      locations of posterior reversible encephalopathy syndrome (PRES) and microbleeds.
      A 58-year-old Chinese woman presented with slurred speech and multiple petechiae
      over lower limbs. Blood tests showed thrombocytopenia. Neuroimaging showed
      multiple acute small infarcts and PRES in the subcortical white matter, basal
      ganglia, thalamus, brainstem and occipital lobe. Microbleeds were noted. She was
      treated as TTP with infusion of cryo-reduced plasma (CRP). Patient subsequently
      developed dense right hemiplegia. Computed tomography of brain demonstrated a new
      major left middle cerebral artery territory infarct. She was stabilized after 2
      weeks of treatment with daily CRP infusion, then received rehabilitation for
      major stroke. Early recognition of TTP provides the best chance of recovery as
      most lesions are reversible when TTP was treated. However, concurrent large
      artery thrombosis could cause major morbidity and mortality. 

PMID- 25988073
TI  - Acute pulmonary edema secondary to hyperbaric oxygen therapy.
AB  - Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment
      of diabetic ulcers, air embolism, carbon monoxide poisoning and gas gangrene with
      minimal adverse effects. Very few cases of HBOT causing acute pulmonary edema
      (PE) has been described; with a study on dogs suggesting that a complication of
      this therapy could be PE. We describe the case of an 80-year-old man with a
      history of stable systolic heart failure and diabetes mellitus presenting with
      acute PE following treatment with HBOT for diabetic foot. 

PMID- 25988074
TI  - Abdominal actinomycosis after laparoscopic cholecystectomy: an uncommon
      presentation of an uncommon problem.
AB  - Actinomycosis is a rare bacterial infection with a broad clinical presentation
      that is seldom reported after elective cholecystectomy. We present an as-of-yet
      unreported case of actinomycosis in an 81-year-old gentleman who was found to
      have right-sided peritonitis and small bowel obstruction 11 months after elective
      laparoscopic cholecystectomy. A complex loculated lesion was found on laparotomy
      with a protracted course of antibiotics being needed for treatment. The rarity of
      this condition will mean it remains a surprise diagnosis to many clinicians.
      However, it is important that clinicians maintain some index of suspicion to
      prevent unnecessary surgery and are aware of the protracted course of antibiotics
      that is needed for successful treatment. 

PMID- 25988075
TI  - Hyperpigmented cutaneous lesions that flare-up with scratching: Darier's sign.
AB  - We present the case of a 40-year-old male with a past medical history of
      urticaria pigmentosa (UP) who presented for consultation to the Allergy clinic
      for an opinion of systemic mastocytosis. Previous workups included elevated serum
      tryptase level, UP on skin biopsy and an increased number of CD117-positive/CD25
      positive mast cells on bone marrow biopsy. This case emphasizes the importance of
      physical findings such as Darier's sign in patients with hyperpigmented lesions,
      which virtually supports the diagnosis UP, raises the suspicion for systemic
      mastocytosis and guides further diagnostic evaluation. This case also outlines
      the management of systemic mastocytosis. 

PMID- 25988076
TI  - A tick-borne illness unmasking asymptomatic Brugada syndrome.
AB  - Brugada syndrome is an important cause of sudden cardiac death and should be
      recognized in asymptomatic patients with characteristic electrocardiographic
      (ECG) findings. We report a case of a 59-year-old male who presented with fever
      and generalized malaise after a camping trip with confirmed tick exposure.
      Initial diagnostic work-up included an ECG, which showed incidental ST-segment
      elevation in the right precordial leads consistent with a type 1 ECG pattern seen
      in Brugada syndrome. He was diagnosed with fever-induced Brugada syndrome and
      treated with doxycycline and antipyretics. The type 1 ECG pattern resolved a few
      hours later with a resultant right bundle branch block. Implantable cardioverter
      defibrillator implantation was not indicated after risk stratification. The case
      highlights the importance of considering Brugada syndrome in patients with
      characteristic ECG changes in the setting of fever, and reviews the latest
      criteria for diagnosis, management and risk stratification of this fatal
      condition. 

PMID- 25988077
TI  - Dramatic response to selective internal radiation therapy for unresectable
      hepatocellular carcinoma.
AB  - A 54-year-old woman with a known history of multifocal hepatocellular carcinoma
      was treated with selective internal radiation therapy (SIRT) using yttrium-90
      ((90)Y) microspheres, despite disease relapses after surgical resection and
      transarterial chemoembolization. She developed a dramatic clinical, radiological
      and metabolic response after 9 weeks. This case provides visual illustration of
      the potential roles of SIRT in the treatment of hepatocellular carcinoma. 

PMID- 25988078
TI  - Fibrous dysplasia of rib presenting as a cystic mass in the lung.
AB  - Fibrous dysplasia (FD) is a benign skeletal disorder that can affect one bone
      (monostotic form) or multiple bones (polyostotic form). It is a non-inherited
      bone disease, in which abnormal differentiation of osteoblasts leads to
      replacement of normal marrow and cancellous bone by immature bone with fibrous
      stroma. It is often asymptomatic and incidentally detected on radiographs. We
      report this rare disorder in a 22-year-old lady who presented to us with cough
      and breathlessness. Her chest radiograph showed a cystic mass extending into the
      chest wall. On computed tomography scan, mass turned out to be FD of the second
      rib. Histopathology of the lesion confirmed the diagnosis. 

PMID- 25988079
TI  - Acute motor axonal neuropathy in a patient with prolonged CD4 depletion due to
      HIV: a local variant of macrophage activation syndrome?
AB  - Acute inflammatory demyelinating polyneuropathy or Guillain-Barre syndrome is
      well recognized as a presenting feature of human immunodeficiency virus (HIV)
      seroconversion and, to a lesser extent, as a complication of HIV infection,
      particularly immune reconstitution. Acute motor axonal neuropathy (AMAN) is much
      rarer in this setting. A case is presented of acute motor neuropathy, with
      features most consistent with AMAN in the setting of congenital HIV and prolonged
      non-compliance with antiretroviral treatment. The case throws new light on the
      pathogenesis of this condition. Macrophage activation is proposed as fundamental;
      the patient was predisposed by HIV as well as the use of granulocyte colony
      stimulating factor and AMAN was then precipitated by a bacterial infection. 

PMID- 25988080
TI  - Mucoepidermoid carcinoma of the lung: a rare entity.
AB  - A 38-year-old lady presented with mild fever and dry cough of 1 week duration.
      Her chest X-ray showed right middle lobe collapse and consolidation. CT thorax
      revealed a mass in the right middle lobe. Subsequent bronchoscopy showed a growth
      completely occluding the right middle lobe bronchus and extending proximally into
      bronchus intermedius. Right bilobectomy (middle and lower lobes) with
      lymphadenectomy was performed. All the histomorphological features were
      suggestive of a low-grade mucoepidermoid carcinoma (MEC). MEC is one of the very
      rare neoplasms of the lung comprising <1% of all lung tumours. Low-grade MEC has
      a better prognosis than high-grade tumour, the latter being similar to that of
      non-small-cell lung carcinoma. 

PMID- 25988081
TI  - Pazopanib induced hand-foot syndrome.

PMID- 25988082
TI  - Longitudinally extensive transverse myelitis as presenting manifestation of small
      cell carcinoma lung.
AB  - Longitudinally extensive transverse myelitis (LETM) is an unusual manifestation
      of systemic malignancy. It has been mainly reported with lung cancers and
      lymphoproliferative malignancy. LETM in systemic malignancy can be caused by
      either intramedullary metastases or paraneoplastic syndrome. We report an unusual
      case of small-cell carcinoma lung, who presented with LETM without having any
      cardinal manifestations of lung malignancy. This case report highlights the
      important differentiating features between intramedullary metastasis and
      paraneoplastic syndrome. 

PMID- 25988083
TI  - Severe short stature and Wolf-Hirschhorn syndrome: response to growth hormone in
      two cases without growth hormone deficiency.
AB  - Wolf-Hirschhorn syndrome (WHS) is a rare congenital disorder occurring in
      approximately 1/50 000 births, with marked pre- and postnatal growth failure. WHS
      results from the hemizygous deletion encompassing the 4p16.3 region. This report
      of two children with WHS shows that growth hormone treatment in selected children
      with WHS and severe short stature may have a substantial effect on long-term
      growth. 

PMID- 25988085
TI  - "Taking my breath away by keeping stress at bay" - an employee assistance program
      in the automotive assembly plant.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of individual
      focused stress management training namely Deep Breathing Exercise (DBE) on self
      perceived occupational stress among male automotive assembly-line workers.
      METHODS: A quasi-experimental study was conducted at 2 automotive assembly plants
      in Malaysia over 9 months, from January 2012 to September 2012. Assembly-line
      workers from Plant A received DBE training while Plant B acted as a control by
      receiving pamphlets on stress and its ill-effects. Intention-to-treat analysis
      was conducted among the self-voluntary respondents in Plant A (n=468) and Plant B
      (n=293). The level of stress was measured using Depression Anxiety Stress Scales
      21 (DASS-21) stress subscale. RESULTS: Significant favorable intervention effects
      were found in Plant A (Effect size=0.6) as compared to Plant B (Effect size=0.2)
      at the end of the study in those receiving DBE. Time and group interaction
      effects were examined using the repeated measure ANOVA test in which there was a
      significant group *time interaction effect [F (1, 1) = 272.45, P<0.001].
      CONCLUSION: The improvement in stress levels showed the potential of DBE training
      as part of Employee Assistance Program in the automotive assembly plant. Future
      studies should be carried out to assess the long term effects of an on-site
      relaxation training to provide stronger evidence for the introduction of DBE
      among assembly-line workers as a coping strategy to alleviate occupational
      stress.

PMID- 25988086
TI  - Using analytic hierarchy process to identify the nurses with high stress-coping
      capability: model and application.
AB  - BACKGROUND: Nurses have long been relied as the major labor force in hospitals.
      Featured with complicated and highly labor-intensive job requirement, multiple
      pressures from different sources was inevitable. Success in identifying stresses
      and accordingly coping with such stresses is important for job performance of
      nurses, and service quality of a hospital. Purpose of this research is to
      identify the determinants of nurses' capabilities. METHODS: A modified Analytic
      Hierarchy Process (AHP) was adopted. Overall, 105 nurses from several randomly
      selected hospitals in southern Taiwan were investigated to generate factors. Ten
      experienced practitioners were included as the expert in the AHP to produce
      weights of each criterion. Six nurses from two regional hospitals were then
      selected to test the model. RESULTS: Four factors are then identified as the
      second level of hierarchy. The study result shows that the family factor is the
      most important factor, and followed by the personal attributes. Top three sub
      criteria that attribute to the nurse's stress-coping capability are children's
      education, good career plan, and healthy family. The practical simulation
      provided evidence for the usefulness of this model. CONCLUSION: The study
      suggested including these key determinants into the practice of human-resource
      management, and restructuring the hospital's organization, creating an employee
      support system as well as a family-friendly working climate. The research
      provided evidence that supports the usefulness of AHP in identifying the key
      factors that help stabilizing a nursing team.

PMID- 25988088
TI  - Occurrence of aflatoxins contamination in brown rice from pakistan.
AB  - BACKGROUND: The objective of this study was to determine the distribution of an
      economically-important class of mycotoxins, the aflatoxins (AFs) in Pakistani
      Brown Rice. METHODS: A total of 262 of brown rice samples were collected from
      different vendors during July 2006 to June 2011. Samples were analyzed for the
      occurrence of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) by thin
      layer chromatography (TLC) technique. RESULTS: AFB1 was detected in 250 (95.4%)
      samples, whereas AFB2 was detected in 20 (7.6%) samples. Furthermore, AFG1 and
      AFG2 were not found in any sample. The contamination range of AFB1 and AFB2 was
      found 1.07-24.65 MUg/kg and 0.52-2.62 MUg/kg, respectively. Total AFs were
      quantified in 250 (95.4%) samples with an average of 3.89 MUg/kg and
      contamination range was noted to be between 1.07-27.27 MUg/kg. The overall
      results indicated that in 12 (4.6%) samples, AFs were not found within detectable
      limits. Furthermore, in 188 (71.7%) samples, AFs level was found below than
      maximum tolerated levels (MTL) as recommended by the European Union (4 MUg/kg).
      Moreover, in 61 (23.3%) samples, AFs range was found between 4-20 MUg/kg, which
      were fit for human consumption as per MTL (20 MUg/kg) assigned by USA (FDA and
      FAO) and Pakistan (PSQCA). While only one sample (27.27 MUg/kg) exceeded the
      above mention regulation limits. CONCLUSION: Low level of AFs occurs frequently
      in brown rice, and can be improved using proper harvesting practices, storage and
      transportation conditions. The small quantities of AFs warrant performing further
      investigation, monitoring and routine analysis on regular basis.

PMID- 25988087
TI  - CDC42-Interacting Protein 4 Gene Is Down Trans-Regulated by HBV DNA polymerase
      Trans Activated Protein 1.
AB  - BACKGROUND: Hepatitis B Virus (HBV) DNA polymerase transactivated protein 1
      (HBVDNAPTP1) is a novel protein transactivated by HBV DNA polymerase, screened by
      suppression subtractive hybridization technique (GenBank accession no: AY450389).
      The biological function of HBVDNAPTP1 was investigated in this study. METHODS: We
      constructed a vector pcDNA3.1 (-)/myc-His A-HBVDNAPTP1 and used it to transfect
      acute monocytic leukemia cell line THP-1. HBVDNAPTP1 expression was detected by
      western blot analysis in the cells. A cDNA library of genes transactivated by
      HBVDNAPTP1 in THP-1 cells was made in pGEM-T Easy using suppression subtractive
      hybridization (SSH). The cDNAs were sequenced and analyzed with BLAST search
      against the sequences in GenBank. RESULTS: Some sequences, such as CIP4, might be
      involved in apoptosis development. mRNA and protein expression of CIP4 was
      identified by Real time RT-PCR and western blot in THP-1 cells. HBVDNAPTP1 could
      down-regulate the expression of CIP4 at both transcription and translation
      levels. CONCLUSION: HBVDNAPTP1 may be involved in the positive regulation on the
      initiation of monocyte apoptosis. The result contribute to reveal the HBVDNAPTP1
      biological functions and provide new evidences for further exploration of the
      regulatory mechanism of HBVDNAPTP1.

PMID- 25988089
TI  - Evaluation of cognitive and behavioral effects of peer education model-based
      intervention to sun safe in children.
AB  - BACKGROUND: There have been many studies that evidence the health hazards of
      sunlight exposure, but less study on sun safe intervention model, especially in
      China. Our aim was to evaluate the cognitive and behavioral effects of a peer
      education model-based intervention to sun safe in children. METHODS: Cluster
      random control intervention was conducted in one district in Chongqing, China.
      Two primary schools, selected through stratified clustered sampling approach (two
      grades in each school, three classes in each grade) were designated as
      intervention (n=304) and control schools (n=305) randomly. 36 students, selected
      as peer educators in intervention group, were trained for one month. Educational
      activities such as discussions were organized by peer educator for one month.
      There was no sun safe education to participants in control school during the
      project period. The evaluation of changes of sun safe knowledge (the primary
      outcome), attitude and behavior (the secondary outcome measures) were conducted
      before intervention and at months of 0, 1 and 6 of the intervention to two groups
      using quantitative and qualitative methods. RESULTS: After the intervention, sun
      safe knowledge score which gained by the students from intervention group has
      been remarkably improved, compared to baseline survey (24.48+/-6.17 vs. 29.51+/
      6.75) (P<0.001), and it kept this high level (29.02+/-7.96 and. 28.65+/-8.96),
      while control group students' scores have made no difference (P=0.410). Most of
      students have changed their sun safe behavior after the intervention. CONCLUSION:
      Peer education program is somewhat effective in some dimensions for improving
      children's understanding of sun safe knowledge and behavior.

PMID- 25988090
TI  - Heavy metal bioabsorption capacity of intestinal helminths in urban rats.
AB  - BACKGROUND: The aim of the present study was to evaluate the capability of
      helminths to absorb heavy metals in comparison with that of the host tissues.
      METHODS: We compared the concentration of cadmium (Cd) and chromium (Cr) in urban
      rats and in their harboring helminthes -Moniliformis moniliformis, Hymenolepis
      diminuta and larval stage of Taenia taenaeiformis (Cysticercus fasciolaris). The
      heavy metal absorption was evaluated in 1g wet weight of parasites and tissues
      digested in nitric acid, using Inductivity Coupled Plasma (ICP_OES). RESULTS: A
      higher concentration of heavy metals was revealed in the helminths than in the
      host tissues. Bioconcentration factor (BF= C in parasite/C in tissue) for both Cd
      and Cr absorption was more than 10-fold higher in M. moniliformis than in the
      three compared host tissues. The BF of Cd in M. moniliformis compared to the
      liver, kidney and muscle of the host was 9.16, 14.14 and 17.09, respectively. BF
      in Cr in the same parasite and the same host tissues ranged from 10.67, 7.06 and
      4.6. High level of absorption in H. diminuta was significantly likewise; the
      individual BF of Cd and Cr in H. diminuta compared to the liver, kidney and
      muscle of the hosts was 4.95, 5.94 and 4.67 vs. 2.67, 11.56 and 5.59. The mean
      concentration of Cd and Cr in C. fasciolaris was also significantly higher than
      that in the rat livers (P<0.007 and P<0.004, respectively). CONCLUSION: This
      study claims that parasites of terrestrial animals exposed to heavy metals can be
      more accurate indicators than the host tissues as new environmental monitoring
      agents.

PMID- 25988091
TI  - Multi-state survival analysis in renal transplantation recipients.
AB  - BACKGROUND: Renal transplantation is a therapy for end-stage renal disease.
      During the study of recipients' survival after renal transplantation, there are
      some events as intermediate events that not only affect the recipients' survival
      but also events which are affected by various factors. The aim of this study was
      to handle these intermediate events in order to identify factors that affect
      recipients' survival by using multi-state models. METHODS: This retrospective
      cohort study included 405 renal transplant patients from Afzalipour Hospital,
      Kerman, Iran, from 2004 to 2010. The survival time of these recipients was
      determined after transplantation and the effect of various factors on the death
      hazard with and without renal allograft failure and hazard of renal allograft
      failure was studied by using multi-state models. RESULTS: During 4.06 years
      (median) of follow-up; 28 (6.9%) recipients died and allograft failure occurred
      in 51 (12.6%) recipients. Based on the results of multi-state model, receiving a
      living kidney transplantation decreased the hazard of renal allograft failure
      (HR=0.38; 95% CI: 0.17- 0.87), pre-transplant hypertension (HR=2.94; 95% CI: 1.54
      5.63) and serum creatinine levels >1.6 upon discharge from the hospital
      (HR=7.38; 95% CI: 3.87- 7.08) increased the hazard of renal allograft failure.
      Receiving living kidney transplantation decreased the hazard of death directly
      (HR=0.18; 95% CI: 0.04- 0.93). CONCLUSION: It was concluded that the effect of
      donor type, pre-transplant hypertension and having serum creatinine >1.6 upon
      discharge from the hospital was significant on hazard of renal allograft failure.
      The only variable that had a direct significant effect on hazard of death was
      donor type.

PMID- 25988092
TI  - A community assessment model appropriate for the Iranian community.
AB  - BACKGROUND: Community assessment is one of the core competencies for public
      health professionals; mainly because it gives them a better understanding of the
      strengths and drawbacks of their jurisdictions. We planned to recognize an
      appropriate model that provides a conceptual framework for the Iranian community.
      METHODS: This study was conducted in Tehran, during 2009-2010 and consisted of
      two parts: a review of the literature and qualitative interview with selected
      experts as well as focus group discussion with health field staff. These steps
      were done to develop a conceptual framework: planning for a steering committee,
      forming a working committee, re-viewing community assessment models and projects,
      preparing the proposed model draft, in-depth interview and focused group
      discussions with national experts, finalizing the draft, and preparing the final
      model. RESULTS: Three different models published and applied routinely in
      different contexts. The 2008 North Carolina Community Assessment model was used
      as a reference. Ten national and 18 international projects were compared to the
      reference and one and six projects were completely compatible with this model,
      respectively. CONCLUSION: Our final proposed model takes communities through
      eight steps to complete a collaborative community assessment: form a community
      assessment team, solicit community participation and gain inter-sectoral
      collaboration, establish a working committee, empower the community, collect and
      analyze community's primary and secondary statistics, solicit community input to
      select health priorities, evaluate the community assessment and develop the
      community assessment document, an develop the community action plans.

PMID- 25988094
TI  - How Iranian women conceptualize mental health: an explanatory model.
AB  - BACKGROUND: In Iran, more than 25% of women suffer from mental disorders. Mental
      disorders and subclinical problems are associated with socioeconomic problem. At
      the community level, mental health promotion can reduce social damage. The aim of
      this study as a part of community based mental health promotion intervention was
      to explore how mental health in Iranian women is viewed. METHODS: According to a
      qualitative method in 2012, participants were selected by purposeful sampling
      from married women 18 to 65 years who are residents in Tehran. Fifteen in depth
      individual interviews were conducted with regard to the concept of mental health,
      causal pathway and help-seeking behavior according to explanatory model. RESULTS:
      Mental health was perceived as the same of emotional well-being. It
      conceptualized not only lack of mental disorder but also sense of satisfaction
      and healthy functioning. According to participant's view, the causal pathway of
      mental health problems were classified to individual, familial and social
      factors. Physical and behavioral problems were related to individual factor, Lack
      of marital adjustment was one of the most important issues in familial item and
      in social factor, cultural context and socio-economic problems were extracted. In
      help seeking process, all of the participants believed that the religion has
      important effect in mental health. CONCLUSION: Marital adjustment is an important
      stage in process of mental health in women.

PMID- 25988093
TI  - Hospital-based incidence of traumatic spinal cord injury in tehran, iran.
AB  - BACKGROUND: The goal of this study was to describe the hospital-based incidence
      of traumatic spinal cord injury in Tehran, Iran. METHODS: We retrospectively
      reviewed the hospital records of traumatic spinal cord injury patients, admitted
      between March 2010 and July 2011 in 61/68 hospitals of Tehran. RESULTS: Overall,
      138 cases of traumatic spinal cord injury were identified. The majority of
      patients were male (84.8%). The mean age was 33.2 +/- 14.3 years. 54.3% patients
      were residing in Tehran and the others were referred from other cities. The mean
      annual incidence of hospitalized traumatic spinal cord injury patients of Tehran
      was 10.5/1,000,000/year (95% confidence interval: 9-12). Fall was the leading
      cause of injury (45.7%), followed by road traffic crash (40.6%). The most common
      cause of tetraplegia (cervical traumatic spinal cord injury) was road traffic
      crash. The duration of hospital stay for tetraplegia and paraplegia (thoracic and
      lumbar traumatic spinal cord injury) was 22.7+/-23.7 and 12.5+/-7.5, respectively
      (P<0.001). Early surgery (surgical decompression within 24 h) was done for 19% of
      the patients. The median day of hospitalization for early and late surgery was
      7.5 and 12, respectively (P=0.044). CONCLUSION: Preventing traumatic spinal cord
      injury should focus on males, age group of 21-30 years, falls and road traffic
      crash. More studies are suggested to evaluate the incidence of non-hospitalized
      traumatic spinal cord injury patients.

PMID- 25988095
TI  - Examine the Relationship between Mindfulness and Drug Craving in Addicts
      Undergoing Methadone Maintenance Treatment.
AB  - BACKGROUND: The aim of this study was examination the relationship between
      mindfulness and drug craving in addicts undergoing methadone maintenance
      treatment. METHODS: The subjects of this research were 80 addicts undergoing
      methadone maintenance treatment selected through available sampling from four
      addiction treatment center in Ahvaz from March 2012 to September 2012. Two
      questionnaires to examine the variables of this study were the five facets
      mindfulness questionnaire (FFMQ) and hero-in craving questionnaire (HCQ). The
      data were analyzed using SPSS version 16. RESULTS: The Pearson correlational
      results indicated significant reverse relation between mindfulness factors and
      craving sub scales (P<0.05). Besides, the regression results indicated that four
      factors of mindfulness such as observation, describing, acting with awareness and
      non-reactivity to inner experience can totally predict 48 percent of craving
      variance (P<0.01 ). CONCLUSION: There is a reverse relation between mindfulness
      and craving. Therefore we advise the researchers in addiction fields that in line
      with various studies that indicated effectiveness of mindfulness based
      interventions in improving various psychological problems, be researcher in
      effectiveness of this intervention in addiction fields. Moreover, we advise the
      addiction therapists to use mindfulness based interventions and technics in order
      to reduction of emotional and cognitive problems co morbidities with addiction
      such as craving that is one of potential factors affecting survival and relapse
      to drug abuse.

PMID- 25988096
TI  - Heat stress and physical capacity: a case study of semi-professional footballers.
AB  - BACKGROUND: The aim of this study was to determine heat stress effect on physical
      capacity of semi-professional footballers in Iran by means of oxygen consumption
      measurement, heart rate monitoring and WBGT assessment environmental conditions.
      METHODS: This study compared two different thermal environmental conditions
      related to sub-maximal exercise and its effect on human physical capacity. Thirty
      two male footballers (age 25.9 +/- 1.4 year; height 176 +/- 2.9 cm and weight 71
      +/- 9.8 kg) were investigated under four workloads (50,100,150 & 200 W) in two
      different thermal conditions in the morning (WBGT=21  degrees C) and afternoon
      (WBGT=33  degrees C) in summer. Each test cycle lasted for 10 minutes with a 10
      min interval for recovery and rest between every workload. In the end of each
      stage, the heart rate, blood pressure, skin temperature and oral temperature were
      measured and recorded. Expired air was collected and its volume was measured
      using standard Douglas bags. The WBGT index was also used to monitor the
      stressful heat condition. RESULTS: Heart rate and VO2 consumption findings for
      different workload showed a significant difference between morning and afternoon
      (P<0.001). HR and VO2 consumption in both morning and afternoon courses showed a
      liner relation (r=0.88, r=0.9 respectively). CONCLUSION: With increasing work
      load beside heat stress, heart rate and oxygen consumption increased. It is
      recommended that with Ta>35  degrees C or WBGT>28  degrees C, physical activates
      and performing exercises should be avoided in order to reduce the risk of heat
      stress-related conditions in athletes.

PMID- 25988097
TI  - The Psychometric Characteristics of the Exercise Benefits/Barriers Scale among
      Iranian Elderly.
AB  - BACKGROUND: The objective of this study was to investigate the validity and
      reliability of the Farsi version of the perceived benefits/barriers scale of
      physical activity in Iranian elderly. METHODS: Overall, 388 elderly subjects (60
      yr and over) completed the demographic characteristics questionnaire, the
      Exercise Benefits/Barriers Scale (EBBS) and the Yale physical activity scale.
      Data were analyzed through of exploratory factor analysis, using Varimax
      rotation, Cronbach's alpha and Pearson correlation. RESULTS: The matrix table of
      rotated elements of Farsi version of EBBS showed ten components, and 41 items
      predicted 61.83% of variance. 28 items in 5 components for benefits of, and 13
      items in 5 components for barriers to physical activity were identified.
      Cronbach's alpha for internal consistency in the whole scale and its subscales
      was 0.83, 0.94 and 0.68. In addition, positive and significant correlation was
      found between overall benefits and their sub-scales as well as between overall
      barriers and their subscales. Moreover, there was significant and positive
      correlation between physical activity and the benefits (r=0.209, P=0.005) and
      significant negative correlation between physical activity and the barriers (r=
      0.231, P=0.001). CONCLUSION: The results showed acceptable reliability and
      validity of the Farsi version of Exercise Benefits/Barriers Scale among Iranian
      elderly.

PMID- 25988098
TI  - Developing a bilingual "persian cued speech" website for parents and
      professionals of children with hearing impairment.
AB  - BACKGROUND: The use of the internet as a source of information gathering, self
      help and support is becoming increasingly recognized. Parents and professionals
      of children with hearing impairment have been shown to seek information about
      different communication approaches online. Cued Speech is a very new approach to
      Persian speaking pupils. Our aim was to develop a useful website to give related
      information about Persian Cued Speech to parents and professionals of children
      with hearing impairment. METHODS: All Cued Speech websites from different
      countries that fell within the first ten pages of Google and Yahoo search-engines
      were assessed. Main subjects and links were studied. All related information was
      gathered from the websites, textbooks, articles etc. RESULTS: Using a framework
      that combined several criteria for health-information websites, we developed the
      Persian Cued Speech website for three distinct audiences (parents, professionals
      and children). CONCLUSION: An accurate, complete, accessible and readable
      resource about Persian Cued Speech for parents and professionals is available
      now.

PMID- 25988099
TI  - Aneurysms of the Sinus of Valsalva in a Patient with Behcet's Disease.
AB  - A 38-year-old man with a history of recurrent genital ulceration initially
      diagnosed as genital herpes was admitted after presenting with paroxysmal
      nocturnal dyspnea. Echocardiography revealed aneurysm formation of the sinus of
      Valsalva. On diagnosis of an aneurysm of the sinus of Valsalva associated with
      Behcet's disease (BD), surgeon repaired the affected sinus only, and continuous
      steroid therapy maintained the integrity. 

PMID- 25988100
TI  - Measles outbreak in South of iran, where vaccine coverage was high: a case-series
      study.
AB  - BACKGROUND: Measles is a highly contagious viral disease that remains an
      important cause of mortality among children despite the availability of a safe
      and effective vaccine around the world. We aimed this study to show a measles out
      break occurring. METHODS: In early 2012, a report of measles outbreak was
      recorded on center for disease control (CDC) of Fars province, south of Iran.
      With this case-series study, characteristics of cases and network transition
      model were described. RESULTS: The primary case was an Afghan refugee who is
      likely to carry the measles virus from its country or from anywhere in Iran to
      Koordeh, a small village in south of Iran. Followed by the Afghan case, 6
      secondary and tertiary cases including rural health worker, were occurred. Except
      a case of 35 year old, in which her vaccination status was unknown, all cases has
      had adherence to vaccination protocol. CONCLUSION: More immunologic and vaccine
      quality investigations are needed to find the main cause of the outbreak.
      Nonetheless, due to the warm weather, probable bad temperature management of cold
      chain and technical problem in vaccination are the main suspicious reasons of the
      outbreak.

PMID- 25988101
TI  - Sanctions against Iran: The Impact on Health Services.

PMID- 25988102
TI  - Desmotology: a black hole in health care.

PMID- 25988103
TI  - Does menthol-brand cigarette initiate early smoking? Evidence from a cross
      sectional study in sarawak, malaysia.

PMID- 25988104
TI  - Multiple sclerosis in parsis: a historical issue.

PMID- 25988105
TI  - Descriptive characteristics of coal workers' pneumoconiosis cases in Turkey.

PMID- 25988106
TI  - Grand challenges in nutrition.

PMID- 25988107
TI  - Grand challenges in nutrition and environmental sustainability.

PMID- 25988108
TI  - Grand challenges in nutrition and food science technology.

PMID- 25988113
TI  - Positive effects of a healthy snack (fruit) versus an unhealthy snack
      (chocolate/crisps) on subjective reports of mental and physical health: a
      preliminary intervention study.
AB  - BACKGROUND/AIMS: Recent research has shown associations between type of snack and
      wellbeing. These studies have been cross-sectional and the aim of the present
      research was to examine this topic using an intervention study. METHODS: A
      between-subjects intervention study was carried out. Volunteers (100 students,
      mean age = 19.00 years; 27 male, 73 female) completed online questionnaires
      measuring anxiety and depression, fatigue, somatic symptoms, cognitive
      difficulties, and distress at baseline. They were then randomly assigned to one
      of two snacking conditions - chocolate/crisps or fruit. Volunteers consumed one
      snack item in the mid-afternoon each day for 10 days. At the end of the
      intervention, the volunteers completed the questionnaires again. RESULTS:
      Analyses of the baseline data confirmed that consumption of chocolate was
      associated with greater emotional eating and depression. Analyses of covariance,
      with the baseline data as covariates, were carried out on the post-intervention
      responses. The results showed that consumption of fruit was associated with lower
      anxiety, depression, and emotional distress than consumption of crisps/chocolate.
      Similarly, scores for somatic symptoms, cognitive difficulties, and fatigue were
      greater in the crisps/chocolate condition. CONCLUSION: These results extend
      findings from cross-sectional studies and give a clearer indication of causal
      effects of different types of snacks on wellbeing.

PMID- 25988109
TI  - Assessment of physical activity and energy expenditure: an overview of objective
      measures.
AB  - The ability to assess energy expenditure (EE) and estimate physical activity (PA)
      in free-living individuals is extremely important in the global context of non
      communicable diseases including malnutrition, overnutrition (obesity), and
      diabetes. It is also important to appreciate that PA and EE are different
      constructs with PA defined as any bodily movement that results in EE and
      accordingly, energy is expended as a result of PA. However, total energy
      expenditure, best assessed using the criterion doubly labeled water (DLW)
      technique, includes components in addition to physical activity energy
      expenditure, namely resting energy expenditure and the thermic effect of food.
      Given the large number of assessment techniques currently used to estimate PA in
      humans, it is imperative to understand the relative merits of each. The goal of
      this review is to provide information on the utility and limitations of a range
      of objective measures of PA and their relationship with EE. The measures
      discussed include those based on EE or oxygen uptake including DLW, activity
      energy expenditure, physical activity level, and metabolic equivalent; those
      based on heart rate monitoring and motion sensors; and because of their
      widespread use, selected subjective measures. 

PMID- 25988110
TI  - Neural responses to visual food cues according to weight status: a systematic
      review of functional magnetic resonance imaging studies.
AB  - Emerging evidence from recent neuroimaging studies suggests that specific food
      related behaviors contribute to the development of obesity. The aim of this
      review was to report the neural responses to visual food cues, as assessed by
      functional magnetic resonance imaging (fMRI), in humans of differing weight
      status. Published studies to 2014 were retrieved and included if they used visual
      food cues, studied humans >18 years old, reported weight status, and included
      fMRI outcomes. Sixty studies were identified that investigated the neural
      responses of healthy weight participants (n = 26), healthy weight compared to
      obese participants (n = 17), and weight-loss interventions (n = 12). High-calorie
      food images were used in the majority of studies (n = 36), however, image
      selection justification was only provided in 19 studies. Obese individuals had
      increased activation of reward-related brain areas including the insula and
      orbitofrontal cortex in response to visual food cues compared to healthy weight
      individuals, and this was particularly evident in response to energy dense cues.
      Additionally, obese individuals were more responsive to food images when
      satiated. Meta-analysis of changes in neural activation post-weight loss revealed
      small areas of convergence across studies in brain areas related to emotion,
      memory, and learning, including the cingulate gyrus, lentiform nucleus, and
      precuneus. Differential activation patterns to visual food cues were observed
      between obese, healthy weight, and weight-loss populations. Future studies
      require standardization of nutrition variables and fMRI outcomes to enable more
      direct comparisons between studies. 

PMID- 25988111
TI  - Approaches for the identification of genetic modifiers of nutrient dependent
      phenotypes: examples from folate.
AB  - By combining the sciences of nutrition, bioinformatics, genomics, population
      genetics, and epidemiology, nutrigenomics is improving our understanding of how
      diet and nutrient intake can interact with or modify gene expression and disease
      risk. In this review, we explore various approaches to examine gene-nutrient
      interactions and the modifying role of nutrient consumption, as they relate to
      nutrient status and disease risk in human populations. Two common approaches
      include the use of SNPs in candidate genes to identify their association with
      nutritional status or disease outcomes, or genome-wide association studies to
      identify genetic polymorphisms associated with a given phenotype. Here, we
      examine the results of various gene-nutrient interaction studies, the association
      of genetic polymorphisms with disease expression, and the identification of
      nutritional factors that modify gene-dependent disease phenotypes. We have
      focused on specific examples from investigations of the interactions of folate, B
      vitamin consumption, and polymorphisms in the genes of B-vitamin dependent
      enzymes and their association with disease risk, followed by an examination of
      the strengths and limitations of the methods employed. We also present
      suggestions for future studies, including an approach from an on-going large
      scale study, to examine the interaction of nutrient intake and genotypic
      variation and their impact on nutritional status. 

PMID- 25988112
TI  - Anti-Proliferation Potential and Content of Fucoidan Extracted from Sporophyll of
      New Zealand Undaria pinnatifida.
AB  - Undaria pinnatifida is a species of brown seaweed known to contain rich amounts
      of fucoidan, a sulfated polysaccharide known to possess various biological
      activities. We isolated crude fucoidan (F0) from the sporophylls of U.
      pinnatifida grown in the Marlborough Sounds, New Zealand. Sulfate content, uronic
      acid content, and molecular weight of F0 were 15.02, 1.24, and >150 kDa,
      respectively. F0 was fractionated to yield three further fractions: F1, F2, and
      F3. Cytotoxicity of two major fractions was determined by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The algal
      fucoidans specifically suppressed the proliferation of three cancer cell lines
      with less cytotoxicity against the normal cells. Selective cytotoxicity could
      relate to the distinctive structures of each fucoidan fraction. Results from this
      study provide evidence that fucoidan, especially from U. pinnatifida grown in New
      Zealand, possesses great potential to be used as a functional food to reduce
      cancer risk or supplement cancer treatment. 

PMID- 25988114
TI  - Dietary Sugars Analysis: Quantification of Fructooligossacharides during
      Fermentation by HPLC-RI Method.
AB  - In this work, a simple chromatographic method is proposed and in-house validated
      for the quantification of total and individual fructooligossacharides (e.g., 1
      kestose, nystose, and 1(F)-fructofuranosylnystose). It was shown that a high
      performance liquid chromatography with refractive index detector could be used to
      monitor the dynamic of fructooligossacharides production via sucrose fermentation
      using Aspergillus aculeatus. This analytical technique may be easily implemented
      at laboratorial or industrial scale for fructooligossacharides mass-production
      monitoring allowing also controlling the main substrate (sucrose) and the
      secondary by-products (glucose and fructose). The proposed chromatographic method
      had a satisfactory intra- and inter-day variability (in general, with a relative
      standard deviation lower than 5%), high sensitivity for each sugar (usually, with
      a relative error lower than 5%), and low detection (lower than 0.06 +/- 0.04 g/L)
      and quantification (lower than 0.2 +/- 0.1 g/L) limits. The correct
      quantification of fructooligossacharides in fermentative media may allow a more
      precise nutritional formulation of new functional foods, since it is reported
      that different fructooligossacharides exhibit different biological activities and
      effects. 

PMID- 25988115
TI  - Improving carotenoid extraction from tomato waste by pulsed electric fields.
AB  - In this investigation, the influence of the application of pulsed electric fields
      (PEFs) of different intensities (3-7 kV/cm and 0-300 MUs) on the carotenoid
      extraction from tomato peel and pulp in a mixture of hexane:acetone:ethanol was
      studied with the aim of increasing extraction yield or reducing the percentage of
      the less green solvents in the extraction medium. According to the cellular
      disintegration index, the optimum treatment time for the permeabilization of
      tomato peel and pulp at different electric field strengths was 90 MUs. The PEF
      permeabilization of tomato pulp did not significantly increase the carotenoid
      extraction. However, a PEF treatment at 5 kV/cm improved the carotenoid
      extraction from tomato peel by 39% as compared with the control in a mixture of
      hexane:ethanol:acetone (50:25:25). Further increments of electric field from 5 to
      7 kV/cm did not increase significantly the extraction of carotenoids. The
      presence of acetone in the solvent mixture did not positively affect the
      carotenoid extraction when the tomato peels were PEF-treated. Response surface
      methodology was used to determine the potential of PEF for reducing the
      percentage of hexane in a hexane:ethanol mixture. The application of a PEF
      treatment allowed reducing the hexane percentage from 45 to 30% without affecting
      the carotenoid extraction yield. The antioxidant capacity of the extracts
      obtained from tomato peel was correlated with the carotenoid concentration and it
      was not affected by the PEF treatment. 

PMID- 25988117
TI  - Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health.
AB  - Zinc supplementation trials in the elderly showed that the incidence of
      infections was decreased by approximately 66% in the zinc group. Zinc
      supplementation also decreased oxidative stress biomarkers and decreased
      inflammatory cytokines in the elderly. In our studies in the experimental model
      of zinc deficiency in humans, we showed that zinc deficiency per se increased the
      generation of IL-1beta and its mRNA in human mononuclear cells following LPS
      stimulation. Zinc supplementation upregulated A20, a zinc transcription factor,
      which inhibited the activation of NF-kappaB, resulting in decreased generation of
      inflammatory cytokines. Oxidative stress and chronic inflammation are important
      contributing factors for several chronic diseases attributed to aging, such as
      atherosclerosis and related cardiac disorders, cancer, neurodegeneration,
      immunologic disorders and the aging process itself. Zinc is very effective in
      decreasing reactive oxygen species (ROS). In this review, the mechanism of zinc
      actions on oxidative stress and generation of inflammatory cytokines and its
      impact on health in humans will be presented. 

PMID- 25988118
TI  - (Ultra) high pressure homogenization for continuous high pressure sterilization
      of pumpable foods - a review.
AB  - Bacterial spores have a strong resistance to both chemical and physical hurdles
      and create a risk for the food industry, which has been tackled by applying high
      thermal intensity treatments to sterilize food. These strong thermal treatments
      lead to a reduction of the organoleptic and nutritional properties of food and
      alternatives are actively searched for. Innovative hurdles offer an alternative
      to inactivate bacterial spores. In particular, recent technological developments
      have enabled a new generation of high pressure homogenizer working at pressures
      up to 400 MPa and thus, opening new opportunities for high pressure sterilization
      of foods. In this short review, we summarize the work conducted on (ultra) high
      pressure homogenization (U)HPH to inactivate endospores in model and food
      systems. Specific attention is given to process parameters (pressure, inlet, and
      valve temperatures). This review gathers the current state of the art and
      underlines the potential of UHPH sterilization of pumpable foods while
      highlighting the needs for future work. 

PMID- 25988116
TI  - Addressing Chronic Malnutrition through Multi-Sectoral, Sustainable Approaches: A
      Review of the Causes and Consequences.
AB  - Chronic malnutrition, including stunting, is an important example of a global
      challenge that spans multiple sectors, specifically health, agriculture, and the
      environment. The objective of this paper is to review current knowledge on the
      causes and consequences of chronic malnutrition and their relationship with
      multiple sectors. Understanding the causes includes approaching chronic
      malnutrition from the basic, underlying, and immediate levels. The causes reach
      from macro-level environmental influences to specific micronutrient intake. In
      order to effectively address stunting, it is important to understand the timing
      of stunting and the ability of individuals to catch up in terms of linear growth,
      cognitive ability, and immune function. The consequences of chronic malnutrition
      are transgenerational and they have an impact at the individual, community, and
      national level in the short- and long-term. There are still many gaps in
      knowledge regarding both the causes and consequences of chronic malnutrition,
      particularly when it comes to the interaction with agriculture and the
      environment, and understanding these gaps is important to addressing the burden
      of chronic malnutrition through evidence-based interventions. 

PMID- 25988119
TI  - Methodological framework: discovering foods or nutrients with a causative
      influence on body weight in free-living settings.
AB  - A significant increase in food availability has been implicated in the worldwide
      obesity epidemic, and there is significant interest in understanding if specific
      foods may contribute to weight gain or aid in weight loss. Many foods have been
      studied in controlled laboratory studies or short-term studies, and these
      findings are often the basis for food-based public health recommendations to
      reduce or prevent obesity. Unfortunately, often these findings are not applicable
      to free-living settings where many interacting factors influence energy balance
      and body weight. Therefore, a proposed set of evidence criteria for making a food
      based public health recommendation to reduce or prevent obesity is outlined and
      discussed herein, to serve as a basis for future committee or panel discussion
      and formalization. Using these criteria as a basis for making strong evidence
      based recommendations will improve the state of science and policy in this area. 

PMID- 25988122
TI  - Rheumatoid cachexia revisited: a metabolic co-morbidity in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease in which pro
      inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, play a
      crucial role. The chronic inflammation, combined with reduced physical activity,
      leads to muscle wasting whereas fat mass would be maintained; the resulting
      abnormal metabolic state is described as rheumatoid cachexia. Since the loss of
      muscle volume would be compensated by the increased fat mass, body mass index
      (BMI) is reported not to reflect the nutritional status in RA patients. The
      implication of rheumatoid cachexia for cardiovascular risk and clinical prognosis
      is not clearly understood, however, adequate control of disease activity in
      combination with appropriate physical exercise could be the most important
      strategy to control rheumatoid cachexia and related metabolic problems. 

PMID- 25988121
TI  - Could dopamine agonists aid in drug development for anorexia nervosa?
AB  - Anorexia nervosa is a severe psychiatric disorder most commonly starting during
      the teenage-years and associated with food refusal and low body weight. Typically
      there is a loss of menses, intense fear of gaining weight, and an often
      delusional quality of altered body perception. Anorexia nervosa is also
      associated with a pattern of high cognitive rigidity, which may contribute to
      treatment resistance and relapse. The complex interplay of state and trait
      biological, psychological, and social factors has complicated identifying
      neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2
      neurotransmitter receptors are involved in motivational aspects of food approach,
      fear extinction, and cognitive flexibility. They could therefore be important
      targets to improve core and associated behaviors in anorexia nervosa. Treatment
      with dopamine antagonists has shown little benefit, and it is possible that
      antagonists over time increase an already hypersensitive dopamine pathway
      activity in anorexia nervosa. On the contrary, application of dopamine receptor
      agonists could reduce circuit responsiveness, facilitate fear extinction, and
      improve cognitive flexibility in anorexia nervosa, as they may be particularly
      effective during underweight and low gonadal hormone states. This article
      provides evidence that the dopamine receptor system could be a key factor in the
      pathophysiology of anorexia nervosa and dopamine agonists could be helpful in
      reducing core symptoms of the disorder. This review is a theoretical approach
      that primarily focuses on dopamine receptor function as this system has been
      mechanistically better described than other neurotransmitters that are altered in
      anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa
      also warrant further study with respect to their interaction with other
      neurotransmitter systems, such as serotonin pathways. 

PMID- 25988120
TI  - Hydroxytyrosol and potential uses in cardiovascular diseases, cancer, and AIDS.
AB  - Hydroxytyrosol is one of the main phenolic components of olive oil. It is present
      in the fruit and leaf of the olive (Olea europaea L.). During the past decades,
      it has been well documented that this phenolic compound has health benefits and a
      protective action has been found in preclinical studies against several diseases.
      Here, we review its bioavailability in human beings and several assays showing
      significant results related with cardiovascular diseases, cancer, and acquired
      immunodeficiency syndrome (AIDS). Mechanisms of action include potent anti
      oxidant and anti-inflammatory effects, among others. The importance of
      hydroxytyrosol in protection of low-density lipoproteins and consequently its
      implication in the reduction of cardiovascular disease risk has been highlighted
      by the European Food Safety Authority, concluding that 5 mg of hydroxytyrosol and
      its derivatives should be consumed daily to reach this effect at physiological
      level. We discuss the potential uses of this compound in supplements, nutraceutic
      foods, or topical formulations in the disease risk reduction. Finally, we
      conclude that more studies are needed to sustain or reject many other health
      claims not yet fully documented and to validate these newly available
      hydroxytyrosol-based products, because it seems to be a good candidate to reduce
      the risk of diseases mentioned. 

PMID- 25988123
TI  - Degradation of Fructans and Production of Propionic Acid by Bacteroides
      thetaiotaomicron are Enhanced by the Shortage of Amino Acids.
AB  - Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes
      its ecosystem by catabolism of various polysaccharides. A model of cross-talk
      between the metabolism of amino acids and fructans in B. thetaiotaomicron was
      proposed. The growth of B. thetaiotaomicron DSM 2079 in two defined media
      containing mineral salts and vitamins, and supplemented with either 20 or 2 amino
      acids, was studied in an isothermal microcalorimeter. The polyfructans inulin
      (from chicory) and levan (synthesized using levansucrase from Pseudomonas
      syringae), two fructooligosaccharide preparations with different composition,
      sucrose and fructose were tested as substrates. The calorimetric power-time
      curves were substrate specific and typically multiauxic. A surplus of amino acids
      reduced the consumption of longer oligosaccharides (degree of polymerization >
      3). Bacterial growth was not detected either in the carbohydrate free medium
      containing amino acids or in the medium with inulin as a sole carbohydrate. In
      amino acid-restricted medium, fermentation leading to acetic acid formation was
      dominant at the beginning of growth (up to 24 h), followed by increased lactic
      acid production, and mainly propionic and succinic acids were produced at the end
      of fermentation. In the medium supplemented with 20 amino acids, the highest
      production of d-lactate (82 +/- 33 mmol/gDW) occurred in parallel with extensive
      consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. The
      production of Ala and Glu was observed at growth on all substrates, and the
      production was enhanced under amino acid deficiency. The study revealed the
      influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed
      that defined growth media are invaluable in elucidating quantitative metabolic
      profiles of the bacteria. Levan was shown to act as an easily degradable
      substrate for B. thetaiotaomicron. The effect of levan on balancing or modifying
      colon microbiota will be studied in further experiments. 

PMID- 25988124
TI  - The Effect of BCMO1 Gene Variants on Macular Pigment Optical Density in Young
      Healthy Caucasians.
AB  - BACKGROUND: Serum lutein (L) and zeaxanthin (Z) positively correlate with macular
      pigment optical density (MPOD); hence, the latter is a valuable indirect tool for
      measuring L and Z content in the macula. L and Z have been attributed antioxidant
      capacity and protection from certain retinal diseases but their uptake within the
      eye is thought to depend on genetic, age, and environmental factors. In
      particular, gene variants within beta-carotene monooxygenase (BCMO1) are thought
      to modulate MPOD in the macula. OBJECTIVES: To determine the effect of BCMO1
      single nucleotide polymorphisms (SNPs) rs11645428, rs6420424, and rs6564851 on
      MPOD in a cohort of young healthy participants of Caucasian origin with normal
      ocular health. DESIGN: In this cohort study, MPOD was assessed in 46 healthy
      participants (22 male and 24 female) with a mean age of 23.8 +/- 4.0 years (range
      19-33). The three SNPs, rs11645428, rs6420424, rs6564851 that have established
      associations with MPOD were determined using MassEXTEND (hME) Sequenom assay. One
      way analysis of variance was performed on groups segregated into homozygous and
      heterozygous BCMO1 genotypes. Correlations between body mass index (BMI), iris
      color, gender, central retinal thickness (CRT), diet, and MPOD were investigated.
      RESULTS: Macular pigment optical density neither significantly varied with BCMO1
      rs11645428 (F 2,41 = 0.70, p = 0.503), rs6420424 (F 2,41 = 0.21, p = 0.801) nor
      rs6464851 homozygous or heterozygous genotypes (F 2,41 = 0,13, p = 0.88), in this
      young healthy cohort. The combination of these three SNPs into triple genotypes
      based on plasma conversion efficiency did not affect MPOD (F 2,41 = 0.07, p =
      0.9). There was a significant negative correlation with MPOD and CRT (r = -0.39,
      p = 0.01) but no significant correlation between BMI, iris color, gender, and
      MPOD. CONCLUSION: Our results indicate that macular pigment deposition within the
      central retina is not dependent on BCMO1 gene variants in young healthy people.
      We propose that MPOD is saturated in younger persons and/or other gene variant
      combinations determine its deposition.

PMID- 25988125
TI  - Natural resources - food nexus: food-related environmental footprints in the
      mediterranean countries.
AB  - Immediate action is required in the Mediterranean to address environmental
      degradation that is mainly driven by consumption patterns. Increasing stress on
      biological and social systems is put by unsustainable consumption patterns. Food
      consumption patterns are important drivers of environment degradation. The
      objective of this review paper is to explore natural resources-food nexus in the
      Mediterranean region by highlighting the environmental footprints of the current
      consumption and production patterns. Secondary data from different sources such
      as FAOSTAT, the World Bank, Water Footprint Network (WFN), and Global Footprint
      Network were used to analyze the situation in 21 Mediterranean countries. The
      region faces many environmental challenges, e.g., land degradation, water
      scarcity, environment pollution, biodiversity loss, and climate change. The
      current consumption patterns imply high ecological, carbon, and water footprints
      of consumption and unfavorable national virtual-water balances. Food Balance
      Sheets data show that the contribution of vegetal and animal-based food product
      groups to food supply is variable among the Mediterranean countries. This has
      implications also in terms of the WF of food supply, which was calculated for
      Bosnia, Egypt, Italy, Morocco, and Turkey. The WF of the current diet resulted
      lower than that of the proposed Mediterranean one in the case of Italy. There is
      a strong scientific evidence supporting assumption that it is so also for other
      Mediterranean countries. The Mediterranean is characterized by a high resource
      use intensity that is further exacerbated by food losses and waste (FLW). In
      fact, FLW implies the loss of precious resources (water, land, energy) and inputs
      (fertilizers). Therefore, it is crucial to increase adherence to the traditional
      Mediterranean diet and to reduce FLW in order to foster transition to more
      sustainable food consumption patterns thus reducing pressure on the scarce
      resources of the Mediterranean region. 

PMID- 25988126
TI  - Nanoemulsion-based delivery systems to improve functionality of lipophilic
      components.
AB  - The use of active lipophilic substances such as antimicrobials and health-related
      compounds in the food industry is still a challenge due to their poor water
      solubility and instability in food formulations. Nano-sized structures such as
      nanoemulsions of oil-in-water are regarded as useful tools with a great potential
      in the food sector to incorporate food ingredients. Reducing the size of the
      active compounds incorporated within a solution would increase the surface area
      per mass unit of nanoemulsions, thus enhancing solubility and stability in foods.
      In addition, the ability of the active lipids to penetrate across biological
      membranes is also enhanced, thus boosting their biological functionality. An
      overview of the most significant studies reporting data about the potential
      benefits of active lipid nanoemulsions over conventional emulsions is presented. 

PMID- 25988127
TI  - Lactate and cancer: revisiting the warburg effect in an era of lactate shuttling.

PMID- 25988128
TI  - Enhancement of Cisplatin sensitivity in human cervical cancer: epigallocatechin-3
      gallate.
AB  - Cisplatin is one of the effective chemotherapeutics in the treatment of several
      types of cancers. However, in addition to the efforts against to its toxicity,
      the amelioration of cisplatin sensitivity is an important point in treatment of
      cervical cancer. To do so, additional substances such as epigallocatechin gallate
      (EGCG), a polyphenol in green tea, have been used in combination with
      chemotherapeutics. We aimed to investigate the possible molecular pathways to
      potentiate cervical cancer cell (HeLa) growth inhibition by combination therapy
      of cisplatin and EGCG. HeLa cells were treated with EGCG (25 MUM), cisplatin (250
      nM), and their combination for 24 h. Cell viability was determined by MTS Assay.
      We analyzed the expressions of NF-kappaB p65, COX-2, Nrf2, HO-1, p-mTOR, p
      p70S6K1, p-4E-BP1, and p-Akt by Western blot analysis. Herein, we have
      demonstrated that EGCG works synergistic with cisplatin in inhibiting growth of
      cervical cancer cells. EGCG improved efficacy of cisplatin treatment in HeLa
      cells by regulating NFkappaB p65, COX-2, p-Akt, and p-mTOR pathways, whereas it
      increased the expression levels of Nrf2/HO-1 in combined therapy. Our
      observations revealed that EGCG increases the sensitization of cisplatin to
      cervical cancer cells by inhibiting cell survival and inducing apoptosis. 

PMID- 25988129
TI  - Dietary Patterns Derived Using Exploratory and Confirmatory Factor Analysis are
      Stable and Generalizable Across Race, Region, and Gender Subgroups in the REGARDS
      Study.
AB  - BACKGROUND: Examining diet as a whole using dietary patterns as exposures is a
      complementary method to using single food or nutrients in studies of diet and
      disease, but the generalizability of intake patterns across race, region, and
      gender in the United States has not been established. OBJECTIVE: To employ
      rigorous statistical analysis to empirically derive dietary patterns in a large
      bi-racial, geographically diverse population and examine whether results are
      stable across population subgroups. DESIGN: The present analysis utilized data
      from 21,636 participants in the Reasons for Geographic and Racial Differences in
      Stroke (REGARDS) study who completed the Block 98 food frequency questionnaire.
      We employed exploratory factor analysis and confirmatory factor analyses on 56
      different food groups iteratively and examined differences by race, region, and
      sex to determine the optimal factor solution in our sample. RESULTS: Five dietary
      patterns emerged: the "Convenience" pattern was characterized by mixed dishes;
      the "Plant-based" pattern by fruits, vegetables, and fish; the "Sweets/Fats"
      pattern by sweet snacks, desserts, and fats and oils; the "Southern" pattern by
      fried foods, organ meat, and sweetened beverages; and the "Alcohol/Salads"
      pattern by beer, wine, liquor, and salads. Differences were most pronounced in
      the Southern pattern with black participants, those residing in the Southeast,
      and participants not completing high school having the highest scores.
      CONCLUSION: Five meaningful dietary patterns emerged in the REGARDS study and
      showed strong congruence across race, sex, and region. Future research will
      examine associations between these patterns and health outcomes to better
      understand racial disparities in disease and inform prevention efforts.

PMID- 25988130
TI  - The Pentapeptide RM-131 Promotes Food Intake and Adiposity in Wildtype Mice but
      Not in Mice Lacking the Ghrelin Receptor.
AB  - The gastrointestinal peptide hormone ghrelin is the endogenous ligand of the
      growth hormone secretagogue receptor (a.k.a. ghrelin receptor, GHR). Currently,
      ghrelin is the only circulating peripheral hormone with the ability to promote a
      positive energy balance by stimulating food intake while decreasing energy
      expenditure and body fat utilization, as defined in rodents. Based on these and
      additional, beneficial effects on metabolism, the endogenous ghrelin system is
      considered an attractive target to treat diverse pathological conditions
      including those associated with eating/wasting disorders and cachexia. As the
      pharmacological potential of ghrelin is hampered by its relatively short half
      life, ghrelin analogs with enhanced pharmacokinetics offer the potential to
      sustainably improve metabolism. One of these ghrelin analogs is the pentapeptide
      RM-131, which promotes food intake and adiposity with higher potency as compared
      to native ghrelin in rodents. Whereas, the effect of RM-131 on energy metabolism
      is solidly confirmed in rodents, it remains elusive whether RM-131 exerts its
      effect solely via the ghrelin receptor. Accordingly, we assessed the receptor
      specificity of RM-131 to promote food intake and adiposity in mice lacking the
      GHR. Our data show that in wildtype mice RM-131 potently promotes weight gain and
      adiposity through stimulation of food intake. However, RM-131 fails to affect
      food intake and body weight in mice lacking the GHR, underlining that the
      anabolic effects of RM-131 are mediated via the ghrelin receptor in mice. 

PMID- 25988132
TI  - Effect of Black Tea and Black Tea Pomace Polyphenols on alpha-Glucosidase and
      alpha-Amylase Inhibition, Relevant to Type 2 Diabetes Prevention.
AB  - This study evaluates the potential mechanism of action and bioactivity of black
      tea and black tea pomace for type 2 diabetes prevention via inhibition of
      carbohydrate hydrolyzing enzymes. Black tea leaves were extracted in hot water
      and black tea pomace was extracted in 70% acetone. The phenolic content of the
      water extract (WBT) and pomace acetone extracts (AOBT) were 5.77 and 8.9 mg/mL,
      respectively, both based on the same concentration of solid tea in the extract.
      The water extract was subjected to C18 extraction and the resulting hydrophobic
      fraction (HBBT) was further subjected to LH-20 extraction to recover a low
      molecular weight phenolic enriched fraction (LMW) and a high molecular weight
      enriched fraction (HMW). The phenolic content of the LMW and HMW fraction were
      1.42 and 2.66 mg/mL, respectively. Among water extracts the HMW fraction was most
      bioactive against alpha-glucosidase (IC50 = 8.97 MUg/mL) followed by HBBT
      fraction (IC50 = 14.83 MUg/mL). However, the HBBT fraction was the most bioactive
      fraction against alpha-amylase (IC50 = 0.049 mg/mL). The black tea pomace (AOBT)
      had significant alpha-glucosidase inhibitory activity (IC50 = 14.72 MUg/mL) but
      lower alpha-amylase inhibitory activity (IC50 = 0.21 mg/mL). The phenolic
      profiles for LMW and HMW fractions were evaluated using HPLC and the differences
      between the two profiles were identified. Further research is underway to
      identify and evaluate the phenolic compounds that are present in the HMW
      fraction. Our findings suggest that black tea and black tea pomace has potential
      for carbohydrate hydrolyzing enzyme inhibition and this activity depends on high
      molecular weight phenolic compounds. 

PMID- 25988131
TI  - Chemical and biochemical mechanisms underlying the cardioprotective roles of
      dietary organopolysulfides.
AB  - Foods that are rich in organosulfides are highly regarded for their broad range
      of functions in disease prevention and health promotion since ancient time yet
      modern scientific study, particularly clinical studies could not agree with
      traditional wisdom. One of the complexities is due to the labile nature of
      organosulfides, which are often transformed to different structures depending on
      the processing conditions. The recent evidence on polysulfides as H2S donors may
      open up a new avenue for establishing structure and health promotion activity
      relationship. To put this development into perspective, we carried out a review
      on the recent progress on the chemistry and biochemistry of organopolysulfides
      with emphasis on their cardioprotective property. First, we briefly surveyed the
      foods that are rich in polysulfides and their structural diversity. This is
      followed by in-depth discussion on the chemical transformations of polysulfides
      under various processing conditions. We further reviewed the potential action
      mechanisms of polysulfides in cardioprotection through: (a) hydrogen sulfide
      releasing activity; (b) radical scavenging activity; and (c) activity in enzyme
      inhibition and intervention of gene regulation pathways. Based on the literature
      trend, we can conclude that the emerging concept of organopolysulfides as
      naturally occurring H2S donors is intriguing and warrants further research to
      establish the structure and activity relationship of the organopolysulfides as
      H2S donors. 

PMID- 25988134
TI  - Effects of high-fructose diets on central appetite signaling and cognitive
      function.
AB  - The consumption of fructose has increased tremendously over the last five
      decades, which is to a large extent due to the development of high-fructose corn
      syrup (HFCS), a commercial sugar additive that contains high amounts of free
      fructose. HFCS is often added to processed food and beverages partly because it
      is a powerful sweetener but even more so because the production is cheap.
      Although fructose in combination with fiber, vitamins, and minerals, as present
      in fruits, is a healthy source of energy, isolated fructose, in processed food
      products has been associated with several health disorders such as insulin
      resistance and hypertension. Apart from its metabolic consequences, a growing
      body of literature suggests that free fructose can also affect neuronal systems.
      High-fructose intake may on the one hand affect central appetite regulation by
      altering specific components of the endocannabinoid system. On the other hand, it
      appears to impact on cognitive function by affecting phosphorylation levels of
      insulin receptor, synapsin 1, and synaptophysin. The present report reviews the
      recent evidence showing a negative effect of free fructose consumption on central
      appetite control, as well as cognitive function. 

PMID- 25988135
TI  - Double sampling with multiple imputation to answer large sample meta-research
      questions: introduction and illustration by evaluating adherence to two simple
      CONSORT guidelines.
AB  - BACKGROUND: Meta-research can involve manual retrieval and evaluation of
      research, which is resource intensive. Creation of high throughput methods (e.g.,
      search heuristics, crowdsourcing) has improved feasibility of large meta-research
      questions, but possibly at the cost of accuracy. OBJECTIVE: To evaluate the use
      of double sampling combined with multiple imputation (DS + MI) to address meta
      research questions, using as an example adherence of PubMed entries to two simple
      consolidated standards of reporting trials guidelines for titles and abstracts.
      METHODS: For the DS large sample, we retrieved all PubMed entries satisfying the
      filters: RCT, human, abstract available, and English language (n = 322, 107). For
      the DS subsample, we randomly sampled 500 entries from the large sample. The
      large sample was evaluated with a lower rigor, higher throughput (RLOTHI) method
      using search heuristics, while the subsample was evaluated using a higher rigor,
      lower throughput (RHITLO) human rating method. Multiple imputation of the missing
      completely at-random RHITLO data for the large sample was informed by: RHITLO
      data from the subsample; RLOTHI data from the large sample; whether a study was
      an RCT; and country and year of publication. RESULTS: The RHITLO and RLOTHI
      methods in the subsample largely agreed (phi coefficients: title = 1.00, abstract
      = 0.92). Compliance with abstract and title criteria has increased over time,
      with non-US countries improving more rapidly. DS + MI logistic regression
      estimates were more precise than subsample estimates (e.g., 95% CI for change in
      title and abstract compliance by year: subsample RHITLO 1.050-1.174 vs. DS + MI
      1.082-1.151). As evidence of improved accuracy, DS + MI coefficient estimates
      were closer to RHITLO than the large sample RLOTHI. CONCLUSION: Our results
      support our hypothesis that DS + MI would result in improved precision and
      accuracy. This method is flexible and may provide a practical way to examine
      large corpora of literature.

PMID- 25988133
TI  - Does Circadian Disruption Play a Role in the Metabolic-Hormonal Link to Delayed
      Lactogenesis II?
AB  - Breastfeeding improves maternal and child health. The American Academy of
      Pediatrics recommends exclusive breastfeeding for 6 months, with continued
      breastfeeding for at least 1 year. However, in the US, only 18.8% of infants are
      exclusively breastfed until 6 months of age. For mothers who initiate
      breastfeeding, the early post-partum period sets the stage for sustained
      breastfeeding. Mothers who experience breastfeeding problems in the early post
      partum period are more likely to discontinue breastfeeding within 2 weeks. A
      major risk factor for shorter breastfeeding duration is delayed lactogenesis II
      (DLII; i.e., onset of milk "coming in" more than 72 h post-partum). Recent
      studies report a metabolic-hormonal link to DLII. This is not surprising because
      around the time of birth the mother's entire metabolism changes to direct
      nutrients to mammary glands. Circadian and metabolic systems are closely linked,
      and our rodent studies suggest circadian clocks coordinate hormonal and metabolic
      changes to support lactation. Molecular and environmental disruption of the
      circadian system decreases a dam's ability to initiate lactation and negatively
      impacts milk production. Circadian and metabolic systems evolved to be functional
      and adaptive when lifestyles and environmental exposures were quite different
      from modern times. We now have artificial lights, longer work days, and increases
      in shift work. Disruption in the circadian system due to shift work, jet-lag,
      sleep disorders, and other modern life style choices are associated with
      metabolic disorders, obesity, and impaired reproduction. We hypothesize that DLII
      is related to disruption of the mother's circadian system. Here, we review
      literature that supports this hypothesis, and describe interventions that may
      help to increase breastfeeding success. 

PMID- 25988136
TI  - Measuring Dietary Restraint Status: Comparisons between the Dietary Intent Scale
      and the Restraint Scale.
AB  - The measurement of young women's self-reported dietary restraint status is
      complex. Compared to Herman and Polivy's commonly utilized Restraint Scale (RS),
      Stice's Dietary Intent Scale (DIS) is less understood. Because the DIS is
      becoming a popular research tool, it is important to understand how this scale
      compares to more traditional measures of restraint. We conducted two
      correlational studies (Study 1 N = 110; Study 2 N = 216) to ascertain the
      similarities and the differences between the DIS and - as a comparison measure -
      the well-researched RS. We explored how the two scales were related to several
      body image variables (e.g., thin-ideal internalization); with a range of self
      regulatory variables (e.g., dispositional self-control); with observed food
      intake during a taste test; and with 18-month weight change (Study 2 only).
      Participants were female University students and were not selected for dieting or
      disordered eating. Unlike RS scores, DIS scores were not significantly correlated
      with the majority of variables tapping into unsuccessful self-regulation.
      However, our data also highlighted similarities between the two restraint scales
      (e.g., association with 18-month weight-loss) and demonstrated that not only were
      participants' DIS scores un-related to unsuccessful self-regulatory variables,
      neither were they related to the variables tapping into successful self
      regulation. 

PMID- 25988137
TI  - Working toward Healthy and Sustainable Diets: The "Double Pyramid Model"
      Developed by the Barilla Center for Food and Nutrition to Raise Awareness about
      the Environmental and Nutritional Impact of Foods.
AB  - The Barilla Center for Food and Nutrition has produced an updated version of the
      traditional food pyramid based on the Mediterranean diet in order to assess the
      simultaneous impact that food has on human health and the environment. The Double
      Pyramid Model demonstrates how the foods recommended to be consumed most
      frequently are also those exerting less environmental impact, whereas the foods
      that should be consumed less frequently are those characterized by a higher
      environmental impact. The environmental impacts resulting from three different
      menus were compared. All menus were equally balanced and comparable in terms of
      nutrition, but they differed in relation to the presence of absence of animal
      flesh and animal products. The first dietary pattern (omnivorous) included both
      animal flesh and products; the second (lacto-ovo-vegetarian) included animal
      products (eggs and dairy) but no flesh; and the third (vegan) was solely plant
      based. The results obtained suggest that a diet based on the principles of the
      Mediterranean diet, as suggested by the Double Pyramid, generates a lower
      environmental impact compared to diets that are heavily based on daily meat
      consumption. 

PMID- 25988139
TI  - Challenges in food chemistry.

PMID- 25988140
TI  - The ecologic validity of fructose feeding trials: supraphysiological feeding of
      fructose in human trials requires careful consideration when drawing conclusions
      on cardiometabolic risk.
AB  - BACKGROUND: Select trials of fructose overfeeding have been used to implicate
      fructose as a driver of cardiometabolic risk. OBJECTIVE: We examined temporal
      trends of fructose dose in human controlled feeding trials of fructose and
      cardiometabolic risk. METHODS: We combined studies from eight meta-analyses on
      fructose and cardiometabolic risk to assess the average fructose dose used in
      these trials. Two types of trials were identified: (1) substitution trials, in
      which energy from fructose was exchanged with equal energy from other
      carbohydrates and (2) addition trials, in which energy from fructose supplemented
      a diet compared to the diet alone. RESULTS: We included 64 substitution trials
      and 16 addition trials. The weighted average fructose dose in substitution trials
      was 101.7 g/day (95% CI: 98.4-105.1 g/day), and the weighted average fructose
      dose in addition trials was 187.3 g/day (95% CI: 181.4-192.9 g/day). CONCLUSION:
      Average fructose dose in substitution and addition trials greatly exceed national
      levels of reported fructose intake (49 +/- 1.0 g/day) (NHANES 1977-2004). Future
      trials using fructose doses at real world levels are needed.

PMID- 25988141
TI  - Exercise training and Beta-alanine-induced muscle carnosine loading.
AB  - PURPOSE: Beta-alanine (BA) supplementation has been shown to augment muscle
      carnosine concentration, thereby promoting high-intensity (HI) exercise
      performance. Trained muscles of athletes have a higher increase in carnosine
      concentration after BA supplementation compared to untrained muscles, but it
      remains to be determined whether this is due to an accumulation of acute exercise
      effects or to chronic adaptations from prior training. The aim of the present
      study was to investigate whether high-volume (HV) and/or HI exercise can improve
      BA-induced carnosine loading in untrained subjects. METHODS: All participants (n
      = 28) were supplemented with 6.4 g/day of BA for 23 days. The subjects were
      allocated to a control group, HV, or HI training group. During the BA
      supplementation period, the training groups performed nine exercise sessions,
      consisting of either 75-90 min continuous cycling at 35-45% Wmax (HV) or 3 to 5
      repeats of 30 s cycling at 165% Wmax with 4 min recovery (HI). Carnosine content
      was measured in soleus and gastrocnemius medialis by proton magnetic resonance
      spectroscopy. RESULTS: There was no difference in absolute increase in carnosine
      content between the groups in soleus and gastrocnemius muscle. For the average
      muscle carnosine content, a higher absolute increase was found in HV (+2.95 mM; P
      = 0.046) and HI (+3.26 mM; P = 0.028) group compared to the control group (+1.91
      mM). However, there was no additional difference between the HV and HI training
      group. CONCLUSION: HV and HI exercise training showed no significant difference
      on BA-induced muscle carnosine loading in soleus and gastrocnemius muscle. It can
      be suggested that there can be a small cumulative effect of exercise on BA
      supplementation efficiency, although differences did not reach significance on
      individual muscle level.

PMID- 25988138
TI  - Exploiting base excision repair to improve therapeutic approaches for pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) is a highly chemoresistant and metastatic
      disease with a dismal 5-year survival rate of 6%. More effective therapeutic
      targets and approaches are urgently needed to tackle this devastating disease.
      The base excision repair (BER) pathway has been identified as a predictor of
      therapeutic response, prognostic factor, and therapeutic target in a variety of
      cancers. This review will discuss our current understanding of BER in PDA and its
      potential to improve PDA treatment. 

PMID- 25988142
TI  - Recent and future grand challenges in protein folding, misfolding, and
      degradation.

PMID- 25988143
TI  - Mathematics's role in the grand challenge of deciphering the molecular basis of
      life.

PMID- 25988144
TI  - New challenges in structural biology: catching the complexity of dynamic
      nanomachines.

PMID- 25988145
TI  - Differences in conformational dynamics within the Hsp90 chaperone family reveal
      mechanistic insights.
AB  - The molecular chaperones of the Hsp90 family are essential in all eukaryotic
      cells. They assist late folding steps and maturation of many different proteins,
      called clients, that are not related in sequence or structure. Hsp90 interaction
      with its clients appears to be coupled to a series of conformational changes.
      Using hydrogen exchange mass spectrometry (HX-MS) we investigated the structural
      dynamics of human Hsp90beta (hHsp90) and yeast Hsp82 (yHsp82). We found that
      eukaryotic Hsp90s are much more flexible than the previously studied Escherichia
      coli homolog (EcHtpG) and that nucleotides induce much smaller changes. More
      stable conformations in yHsp82 are obtained in presence of co-chaperones. The
      tetratricopeptide repeat (TPR) domain protein Cpr6 causes a different amide
      proton protection pattern in yHsp82 than the previously studied TPR-domain
      protein Sti1. In the simultaneous presence of Sti1 and Cpr6, protection levels
      are observed that are intermediate between the Sti1 and the Cpr6 induced changes.
      Surprisingly, no bimodal distributions of the isotope peaks are detected,
      suggesting that both co-chaperones affect both protomers of the Hsp90 dimer in a
      similar way. The cochaperones Sba1 was found previously in the crystal structure
      bound to the ATP hydrolysis-competent conformation of Hsp90, which did not allow
      to distinguish the mode of Sba1-mediated inhibition of Hsp90's ATPase activity by
      stabilizing the pre- or post-hydrolysis step. Our HX-MS experiments now show that
      Sba1 binding leads to a protection of the ATP binding lid, suggesting that it
      inhibits Hsp90's ATPase activity by slowing down product release. This hypothesis
      was verified by a single-turnover ATPase assay. Together, our data suggest that
      there are much smaller energy barriers between conformational states in
      eukaryotic Hsp90s than in EcHtpG and that co-chaperones are necessary in addition
      to nucleotides to stabilize defined conformational states. 

PMID- 25988146
TI  - Efficient and stable reconstitution of the ABC transporter BmrA for solid-state
      NMR studies.
AB  - We present solid-state NMR sample preparation and first 2D spectra of the
      Bacillus subtilis ATP-binding cassette (ABC) transporter BmrA, a membrane protein
      involved in multidrug resistance. The homodimeric 130-kDa protein is a challenge
      for structural characterization due to its membrane-bound nature, size, inherent
      flexibility and insolubility. We show that reconstitution of this protein in
      lipids from Bacillus subtilis at a lipid-protein ratio of 0.5 w/w allows for
      optimal protein insertion in lipid membranes with respect to two central NMR
      requirements, high signal-to-noise in the spectra and sample stability over a
      time period of months. The obtained spectra point to a well-folded protein and a
      highly homogenous preparation, as witnessed by the narrow resonance lines and the
      signal dispersion typical for the expected secondary structure distribution of
      BmrA. This opens the way for studies of the different conformational states of
      the transporter in the export cycle, as well as on interactions with substrates,
      via chemical-shift fingerprints and sequential resonance assignments. 

PMID- 25988148
TI  - Synergism between a foldase and an unfoldase: reciprocal dependence between the
      thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK.
AB  - The role of bacterial Hsp40, DnaJ, is to co-chaperone the binding of misfolded or
      alternatively folded proteins to bacterial Hsp70, DnaK, which is an ATP-fuelled
      unfolding chaperone. In addition to its DnaK targeting activity, DnaJ has a weak
      thiol-reductase activity. In between the substrate-binding domain and the J
      domain anchor to DnaK, DnaJ has a unique domain with four conserved CXXC motives
      that bind two Zn(2+) and partly contribute to polypeptide binding. Here, we
      deleted in DnaJ this Zn-binding domain, which is characteristic to type I but not
      of type II or III J-proteins. This caused a loss of the thiol-reductase activity
      and strongly reduced the ability of DnaJ to mediate the ATP- and DnaK-dependent
      unfolding/refolding of mildly oxidized misfolded polypeptides, an inhibition that
      was alleviated in the presence of thioredoxin or DTT. We suggest that in addition
      to their general ability to target misfolded polypeptide substrates to the
      Hsp70/Hsp110 chaperone machinery, Type I J-proteins carry an ancillary protein
      dithiol-isomerase function that can synergize the unfolding action of the
      chaperone, in the particular case of substrates that are further stabilized by
      non-native disulfide bonds. Whereas the unfoldase can remain ineffective without
      the transient untying of disulfide bonds by the foldase, the foldase can remain
      ineffective without the transient ATP-fuelled unfolding of wrong local structures
      by the unfoldase. 

PMID- 25988149
TI  - The OncoFinder algorithm for minimizing the errors introduced by the high
      throughput methods of transcriptome analysis.
AB  - The diversity of the installed sequencing and microarray equipment make it
      increasingly difficult to compare and analyze the gene expression datasets
      obtained using the different methods. Many applications requiring high-quality
      and low error rates cannot make use of available data using traditional
      analytical approaches. Recently, we proposed a new concept of signalome-wide
      analysis of functional changes in the intracellular pathways termed OncoFinder, a
      bioinformatic tool for quantitative estimation of the signaling pathway
      activation (SPA). We also developed methods to compare the gene expression data
      obtained using multiple platforms and minimizing the error rates by mapping the
      gene expression data onto the known and custom signaling pathways. This technique
      for the first time makes it possible to analyze the functional features of
      intracellular regulation on a mathematical basis. In this study we show that the
      OncoFinder method significantly reduces the errors introduced by transcriptome
      wide experimental techniques. We compared the gene expression data for the same
      biological samples obtained by both the next generation sequencing (NGS) and
      microarray methods. For these different techniques we demonstrate that there is
      virtually no correlation between the gene expression values for all datasets
      analyzed (R (2) < 0.1). In contrast, when the OncoFinder algorithm is applied to
      the data we observed clear-cut correlations between the NGS and microarray gene
      expression datasets. The SPA profiles obtained using NGS and microarray
      techniques were almost identical for the same biological samples allowing for the
      platform-agnostic analytical applications. We conclude that this feature of the
      OncoFinder enables to characterize the functional states of the transcriptomes
      and interactomes more accurately as before, which makes OncoFinder a method of
      choice for many applications including genetics, physiology, biomedicine, and
      molecular diagnostics. 

PMID- 25988151
TI  - Differentiated thyroid cancer in patients with resistance to thyroid hormone
      syndrome. A novel case and a review of the literature.
AB  - Resistance to thyroid hormone (RTH) represents a syndrome in which patients
      present elevated circulating thyroid hormones in the presence of non-suppressed
      TSH. We report a novel case where a patient with RTH presented a differentiated
      thyroid cancer. A19 year-old female had been referred due to thyroid disease that
      disclosed features characteristic of a RTH. During the follow up it was detected
      a follicular tumor that led to the recommendation for thyroid surgical ablation,
      where an incidental papillary thyroid microcarcinoma (mPTC) was found. The
      increase of thyroglobulin (TG) levels following thyroid removal referred the
      patient for radioiodine treatment. Post-treatment, it was detected jugular
      adenopathies and the patient was subjected to cervical lymph node drainage where
      metastases of the mPTC were found. RTH syndrome was confirmed by the detection of
      a THRB germline mutation. A BRAF mutation was also found in the mPTC but not
      detected in the follicular adenoma or normal adjacent tissue. The young age of
      the patient, the rarity of BRAF mutations in childhood and the high dissemination
      of the malignancy, lead us to the speculation that increased TSH stimulation in a
      RTH background and oncogenic activation of BRAF could have served as (co) drivers
      and might have triggered an advanced stage of the neoplastic disease. These
      findings together with a review of published cases add novel information to the
      management of RTH patients with differentiated thyroid cancer. 

PMID- 25988150
TI  - Differential effects of glycation on protein aggregation and amyloid formation.
AB  - Amyloids are a class of insoluble proteinaceous substances generally composed of
      linear un-branched fibrils that are formed from misfolded proteins.
      Conformational diseases such as Alzheimer's disease, transmissible spongiform
      encephalopathies, and familial amyloidosis are associated with the presence of
      amyloid aggregates in the affected tissues. The majority of the cases are
      sporadic, suggesting that several factors must contribute to the onset and
      progression of these disorders. Among them, in the past 10 years, non-enzymatic
      glycation of proteins has been reported to stimulate protein aggregation and
      amyloid deposition. In this review, we analyze the most recent advances in this
      field suggesting that the effects induced by glycation may not be generalized as
      strongly depending on the protein structure. Indeed, being a post-translational
      modification, glycation could differentially affects the aggregation process in
      promoting, accelerating and/or stabilizing on-pathway and off-pathway species. 

PMID- 25988152
TI  - Temporal resolution in fluorescence imaging.
AB  - Temporal resolution is a key factor for imaging rapidly occurring events in
      biology. In this feature article, I investigate an approximate estimate for
      determining the temporal resolution limit. The condition that led to this limit
      is, the time taken by the ensemble (99.9%) of excited molecules to relax to
      ground state, assuming all the emitted photons are detected. In a simplistic
      three-level system, the temporal resolution is, ~3tau p , where tau p = (log e
      10)/(kf + knr ) and, kf and knr are respectively the radiative and non-radiative
      emission rates. This further assumes the ideal condition that, the quantum
      efficiency of the detector is unity and there are no other loses. We discuss few
      state-of-art microscopy techniques that are capable of high temporal resolution.
      This includes techniques such as multifocal multiphoton microscopy (MMM),
      multifocal plane microscopy, multiple excitation spot optical microscopy (MESO),
      multiplane microscopy and multiple light-sheet microscopy (MLSM). 

PMID- 25988147
TI  - Wrecked regulation of intrinsically disordered proteins in diseases:
      pathogenicity of deregulated regulators.
AB  - Biologically active proteins without stable tertiary structure are common in all
      known proteomes. Functions of these intrinsically disordered proteins (IDPs) are
      typically related to regulation, signaling, and control. Cellular levels of these
      important regulators are tightly regulated by a variety mechanisms ranging from
      firmly controlled expression to precisely targeted degradation. Functions of IDPs
      are controlled by binding to specific partners, alternative splicing, and
      posttranslational modifications among other means. In the norm, right amounts of
      precisely activated IDPs have to be present in right time at right places.
      Wrecked regulation brings havoc to the ordered world of disordered proteins,
      leading to protein misfolding, misidentification, and missignaling that give rise
      to numerous human diseases, such as cancer, cardiovascular disease,
      neurodegenerative diseases, and diabetes. Among factors inducing pathogenic
      transformations of IDPs are various cellular mechanisms, such as chromosomal
      translocations, damaged splicing, altered expression, frustrated
      posttranslational modifications, aberrant proteolytic degradation, and defective
      trafficking. This review presents some of the aspects of deregulated regulation
      of IDPs leading to human diseases. 

PMID- 25988154
TI  - Trapping a salt-dependent unfolding intermediate of the marginally stable protein
      Yfh1.
AB  - Yfh1, the yeast ortholog of frataxin, is a protein of limited thermodynamic
      stability which undergoes cold denaturation at temperatures above the water
      freezing point. We have previously demonstrated that its stability is strongly
      dependent on ionic strength and that monovalent or divalent cations are able to
      considerably stabilize the fold. Here, we present a study of the folded state and
      of the structural determinants that lead to the strong salt dependence. We
      demonstrate by nuclear magnetic resonance that, at room temperature, Yfh1 exists
      as an equilibrium mixture of a folded species and a folding intermediate in slow
      exchange equilibrium. The equilibrium completely shifts in favor of the folded
      species by the addition of even small concentrations of salt. We demonstrate that
      Yfh1 is destabilized by a localized energetic frustration arising from an
      "electrostatic hinge" made of negatively charged residues mapped in the beta
      sheet. Salt interactions at this site have a "frustration-relieving" effect. We
      discuss the consequences of our findings for the function of Yfh1 and for our
      understanding of protein folding stability. 

PMID- 25988153
TI  - Structural mechanisms of chaperone mediated protein disaggregation.
AB  - The ClpB/Hsp104 and Hsp70 classes of molecular chaperones use ATP hydrolysis to
      dissociate protein aggregates and complexes, and to move proteins through
      membranes. ClpB/Hsp104 are members of the AAA+ family of proteins which form ring
      shaped hexamers. Loops lining the pore in the ring engage substrate proteins as
      extended polypeptides. Interdomain rotations and conformational changes in these
      loops coupled to ATP hydrolysis unfold and pull proteins through the pore. This
      provides a mechanism that progressively disrupts local secondary and tertiary
      structure in substrates, allowing these chaperones to dissociate stable
      aggregates such as beta-sheet rich prions or coiled coil SNARE complexes. While
      the ClpB/Hsp104 mechanism appears to embody a true power-stroke in which an ATP
      powered conformational change in one protein is directly coupled to movement or
      structural change in another, the mechanism of force generation by Hsp70s is
      distinct and less well understood. Both active power-stroke and purely passive
      mechanisms in which Hsp70 captures spontaneous fluctuations in a substrate have
      been proposed, while a third proposed mechanism-entropic pulling-may be able to
      generate forces larger than seen in ATP-driven molecular motors without the
      conformational coupling required for a power-stroke. The disaggregase activity of
      these chaperones is required for thermotolerance, but unrestrained protein
      complex/aggregate dissociation is potentially detrimental. Disaggregating
      chaperones are strongly auto-repressed, and are regulated by co-chaperones which
      recruit them to protein substrates and activate the disaggregases via mechanisms
      involving either sequential transfer of substrate from one chaperone to another
      and/or simultaneous interaction of substrate with multiple chaperones. By
      effectively subjecting substrates to multiple levels of selection by multiple
      chaperones, this may insure that these potent disaggregases are only activated in
      the appropriate context. 

PMID- 25988155
TI  - The conformation of enkephalin bound to its receptor: an "elusive goal" becoming
      reality.
AB  - The availability of solid state structures of opioid receptors has prompted us to
      reconsider a crucial question concerning bioactive peptides: can their
      conformation be studied without any knowledge of the structure of their
      receptors? The possibility of giving a meaningful answer to this query rests
      ultimately on the ease of dealing with the flexibility of bioactive peptides, and
      amongst them one of the most flexible bioactive peptides, enkephalin. All
      solution studies of enkephalin hint at an inextricable mixture of quasi
      isoenergetic conformers. In this study we refer to the only NMR work that yielded
      inter-residue NOEs, performed at very low temperature. In the present work, we
      have used the simplest possible docking methods to check the consistency of the
      main conformers of enkephalin with the steric requirements of the active site of
      the receptor, as provided by the crystal structure of its complex with
      naltrindole, a rigid antagonist. We show that the conformers found in the
      equilibrium mixture at low temperature are indeed compatible with a good fit to
      the receptor active site. The possible uncertainties linked to the different
      behavior of agonists and antagonists do not diminish the relevance of the
      finding. 

PMID- 25988156
TI  - Nanoparticle-facilitated functional and molecular imaging for the early detection
      of cancer.
AB  - Cancer detection in its early stages is imperative for effective cancer treatment
      and patient survival. In recent years, biomedical imaging techniques, such as
      magnetic resonance imaging, computed tomography and ultrasound have been greatly
      developed and have served pivotal roles in clinical cancer management. Molecular
      imaging (MI) is a non-invasive imaging technique that monitors biological
      processes at the cellular and sub-cellular levels. To achieve these goals, MI
      uses targeted imaging agents that can bind targets of interest with high
      specificity and report on associated abnormalities, a task that cannot be
      performed by conventional imaging techniques. In this respect, MI holds great
      promise as a potential therapeutic tool for the early diagnosis of cancer.
      Nevertheless, the clinical applications of targeted imaging agents are limited
      due to their inability to overcome biological barriers inside the body. The use
      of nanoparticles has made it possible to overcome these limitations. Hence,
      nanoparticles have been the subject of a great deal of recent studies. Therefore,
      developing nanoparticle-based imaging agents that can target tumors via active or
      passive targeting mechanisms is desirable. This review focuses on the
      applications of various functionalized nanoparticle-based imaging agents used in
      MI for the early detection of cancer. 

PMID- 25988158
TI  - An evolutionary perspective on the Crabtree effect.
AB  - The capability to ferment sugars into ethanol is a key metabolic trait of yeasts.
      Crabtree-positive yeasts use fermentation even in the presence of oxygen, where
      they could, in principle, rely on the respiration pathway. This is surprising
      because fermentation has a much lower ATP yield than respiration (2 ATP vs.
      approximately 18 ATP per glucose). While genetic events in the evolution of the
      Crabtree effect have been identified, the selective advantages provided by this
      trait remain controversial. In this review we analyse explanations for the
      emergence of the Crabtree effect from an evolutionary and game-theoretical
      perspective. We argue that an increased rate of ATP production is likely the most
      important factor behind the emergence of the Crabtree effect. 

PMID- 25988159
TI  - Application of statistical process control to qualitative molecular diagnostic
      assays.
AB  - Modern pathology laboratories and in particular high throughput laboratories such
      as clinical chemistry have developed a reliable system for statistical process
      control (SPC). Such a system is absent from the majority of molecular
      laboratories and where present is confined to quantitative assays. As the
      inability to apply SPC to an assay is an obvious disadvantage this study aimed to
      solve this problem by using a frequency estimate coupled with a confidence
      interval calculation to detect deviations from an expected mutation frequency.
      The results of this study demonstrate the strengths and weaknesses of this
      approach and highlight minimum sample number requirements. Notably, assays with
      low mutation frequencies and detection of small deviations from an expected value
      require greater sample numbers to mitigate a protracted time to detection.
      Modeled laboratory data was also used to highlight how this approach might be
      applied in a routine molecular laboratory. This article is the first to describe
      the application of SPC to qualitative laboratory data. 

PMID- 25988157
TI  - Standing of nucleic acid testing strategies in veterinary diagnosis laboratories
      to uncover Mycobacterium tuberculosis complex members.
AB  - Nucleic acid testing (NAT) designate any molecular approach used for the
      detection, identification, and characterization of pathogenic microorganisms,
      enabling the rapid, specific, and sensitive diagnostic of infectious diseases,
      such as tuberculosis. These assays have been widely used since the 90s of the
      last century in human clinical laboratories and, subsequently, also in veterinary
      diagnostics. Most NAT strategies are based in the polymerase chain reaction (PCR)
      and its several enhancements and variations. From the conventional PCR, real-time
      PCR and its combinations, isothermal DNA amplification, to the nanotechnologies,
      here we review how the NAT assays have been applied to decipher if and which
      member of the Mycobacterium tuberculosis complex is present in a clinical sample.
      Recent advances in DNA sequencing also brought new challenges and have made
      possible to generate rapidly and at a low cost, large amounts of sequence data.
      This revolution with the high-throughput sequencing (HTS) technologies makes
      whole genome sequencing (WGS) and metagenomics the trendiest NAT strategies,
      today. The ranking of NAT techniques in the field of clinical diagnostics is
      rising, and we provide a SWOT (Strengths, Weaknesses, Opportunities, and Threats)
      analysis with our view of the use of molecular diagnostics for detecting
      tuberculosis in veterinary laboratories, notwithstanding the gold standard being
      still the classical culture of the agent. The complementary use of both classical
      and molecular diagnostics approaches is recommended to speed the diagnostic,
      enabling a fast decision by competent authorities and rapid tackling of the
      disease. 

PMID- 25988160
TI  - Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing.
AB  - Antibiotic resistance in Helicobacter pylori (H.pylori) is the main factor
      affecting the efficacy of current treatment methods against infection caused by
      this organism. The traditional culture methods for testing bacterial
      susceptibility to antibiotics are expensive and require 10-14 days. Since
      resistance to clarithromycin, fluoroquinolone, and tetracycline seems to be
      exclusively caused by specific mutations in a small region of the responsible
      gene, molecular methods offer an attractive alternative to the above-mentioned
      techniques. The technique of polymerase chain reaction (PCR) is an accurate and
      rapid method for the detection of mutations that confer antibiotic resistance.
      This review highlights the mechanisms of antibiotic resistance in H. pylori and
      the molecular methods for antibiotic susceptibility testing. 

PMID- 25988161
TI  - Endophilin-A1 BAR domain interaction with arachidonyl CoA.
AB  - Endophilin-A1 belongs to the family of BAR domain containing proteins that
      catalyze membrane remodeling processes via sensing, inducing and stabilizing
      membrane curvature. We show that the BAR domain of endophilin-A1 binds
      arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA
      into a defined structure. We studied low resolution structures of endophilin-A1
      BAR and its complex with arachidonyl-CoA in solution using synchrotron small
      angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be
      dimeric at lower concentrations but builds tetramers and higher order complexes
      with increasing concentrations. Extensive titration SAXS studies revealed that
      the BAR domain produces a homogenous complex with the lipid micelles. The
      structural model of the complexes revealed two arachidonyl-CoA micelles bound to
      the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the
      bound micelles significantly decreases compared to that of the free micelles, and
      this structural result may provide hints on the potential biological relevance of
      the endophilin-A1-BAR interaction with arachidonyl CoA. 

PMID- 25988162
TI  - Challenging muscle homeostasis uncovers novel chaperone interactions in
      Caenorhabditis elegans.
AB  - Proteome stability is central to cellular function and the lifespan of an
      organism. This is apparent in muscle cells, where incorrect folding and assembly
      of the sarcomere contributes to disease and aging. Apart from the myosin-assembly
      factor UNC-45, the complete network of chaperones involved in assembly and
      maintenance of muscle tissue is currently unknown. To identify additional factors
      required for sarcomere quality control, we performed genetic screens based on
      suppressed or synthetic motility defects in Caenorhabditis elegans. In addition
      to ethyl methyl sulfonate-based mutagenesis, we employed RNAi-mediated knockdown
      of candidate chaperones in unc-45 temperature-sensitive mutants and screened for
      impaired movement at permissive conditions. This approach confirmed the
      cooperation between UNC-45 and Hsp90. Moreover, the screens identified three
      novel co-chaperones, CeHop (STI-1), CeAha1 (C01G10.8) and Cep23 (ZC395.10),
      required for muscle integrity. The specific identification of Hsp90 and Hsp90 co
      chaperones highlights the physiological role of Hsp90 in myosin folding. Our work
      thus provides a clear example of how a combination of mild perturbations to the
      proteostasis network can uncover specific quality control modules. 

PMID- 25988163
TI  - Linking metabolomics data to underlying metabolic regulation.
AB  - The comprehensive experimental analysis of a metabolic constitution plays a
      central role in approaches of organismal systems biology. Quantifying the impact
      of a changing environment on the homeostasis of cellular metabolism has been the
      focus of numerous studies applying various metabolomics techniques. It has been
      proven that approaches which integrate different analytical techniques, e.g., LC
      MS, GC-MS, CE-MS and H-NMR, can provide a comprehensive picture of a certain
      metabolic homeostasis. Identification of metabolic compounds and quantification
      of metabolite levels represent the groundwork for the analysis of regulatory
      strategies in cellular metabolism. This significantly promotes our current
      understanding of the molecular organization and regulation of cells, tissues and
      whole organisms. Nevertheless, it is demanding to elicit the pertinent
      information which is contained in metabolomics data sets. Based on the central
      dogma of molecular biology, metabolite levels and their fluctuations are the
      result of a directed flux of information from gene activation over transcription
      to translation and posttranslational modification. Hence, metabolomics data
      represent the summed output of a metabolic system comprising various levels of
      molecular organization. As a consequence, the inverse assignment of metabolomics
      data to underlying regulatory processes should yield information which-if
      deciphered correctly-provides comprehensive insight into a metabolic system. Yet,
      the deduction of regulatory principles is complex not only due to the high number
      of metabolic compounds, but also because of a high level of cellular
      compartmentalization and differentiation. Motivated by the question how
      metabolomics approaches can provide a representative view on regulatory
      biochemical processes, this article intends to present and discuss current
      metabolomics applications, strategies of data analysis and their limitations with
      respect to the interpretability in context of biological processes. 

PMID- 25988166
TI  - Immunity of the Saccharomyces cerevisiae SSY5 mRNA to nonsense-mediated mRNA
      decay.
AB  - The nonsense-mediated mRNA decay (NMD) pathway is a specialized pathway that
      triggers the rapid degradation of select mRNAs. Initially, identified as a
      pathway that degrades mRNAs with premature termination codons, NMD is now
      recognized as a pathway that also regulates some natural mRNAs. Since natural
      mRNAs do not typically contain premature termination codons, these mRNAs contain
      features that target them to NMD. In Saccharomyces cerevisiae mRNAs with
      atypically long 3'-UTRs are usually degraded by NMD, however in some conditions a
      constitutively expressed SSY5 mRNA with multiple NMD targeting signals including
      an atypically long 3'-UTR is an exception. We investigated the features of the
      SSY5 mRNAs that confer immunity to NMD. We found that the SSY5 mRNA 3'-UTRs are
      sufficient to target NMD insensitive mRNA to the pathway. Replacing the SSY5 3'
      UTRs with the cyc1-512 3'-UTRs, known to target mRNAs to NMD or with the CYC1 3'
      UTR, known not to target mRNAs to NMD, resulted in production of SSY5 mRNAs that
      were regulated by NMD. These observations suggest that the SSY5 mRNAs require
      sequences both within the 5'-UTR and/or ORF as well as the 3'-UTR to escape decay
      by NMD. 

PMID- 25988165
TI  - Biological response of cancer cells to radiation treatment.
AB  - Cancer is a class of diseases characterized by uncontrolled cell growth and has
      the ability to spread or metastasize throughout the body. In recent years,
      remarkable progress has been made toward the understanding of proposed hallmarks
      of cancer development, care, and treatment modalities. Radiation therapy or
      radiotherapy is an important and integral component of cancer management, mostly
      conferring a survival benefit. Radiation therapy destroys cancer by depositing
      high-energy radiation on the cancer tissues. Over the years, radiation therapy
      has been driven by constant technological advances and approximately 50% of all
      patients with localized malignant tumors are treated with radiation at some point
      in the course of their disease. In radiation oncology, research and development
      in the last three decades has led to considerable improvement in our
      understanding of the differential responses of normal and cancer cells. The
      biological effectiveness of radiation depends on the linear energy transfer
      (LET), total dose, number of fractions and radiosensitivity of the targeted cells
      or tissues. Radiation can either directly or indirectly (by producing free
      radicals) damages the genome of the cell. This has been challenged in recent
      years by a newly identified phenomenon known as radiation induced bystander
      effect (RIBE). In RIBE, the non-irradiated cells adjacent to or located far from
      the irradiated cells/tissues demonstrate similar responses to that of the
      directly irradiated cells. Understanding the cancer cell responses during the
      fractions or after the course of irradiation will lead to improvements in
      therapeutic efficacy and potentially, benefitting a significant proportion of
      cancer patients. In this review, the clinical implications of radiation induced
      direct and bystander effects on the cancer cell are discussed. 

PMID- 25988164
TI  - Protein folding as a driving force for dual protein targeting in eukaryotes.
AB  - It is well documented that in eukaryotic cells molecules of one protein can be
      located in several subcellular locations, a phenomenon termed dual targeting,
      dual localization, or dual distribution. The differently localized identical or
      nearly identical proteins are termed "echoforms." Our conventional definition of
      dual targeted proteins refers to situations in which one of the echoforms is
      translocated through/into a membrane. Thus, dual targeted proteins are recognized
      by at least one organelle's receptors and translocation machineries within the
      lipid bilayer. In this review we attempt to evaluate mechanisms and situations in
      which protein folding is the major determinant of dual targeting and of the
      relative distribution levels of echoforms in the subcellular compartments of the
      eukaryotic cell. We show that the decisive folding step can occur prior, during
      or after translocation through the bilayer of a biological membrane. This
      phenomenon involves folding catalysts in the cell such as chaperones, proteases
      and modification enzymes, and targeting processes such as signal recognition,
      translocation through membranes, trapping, retrotranslocation and reverse
      translocation. 

PMID- 25988167
TI  - How round is a protein? Exploring protein structures for globularity using
      conformal mapping.
AB  - We present a new algorithm that automatically computes a measure of the geometric
      difference between the surface of a protein and a round sphere. The algorithm
      takes as input two triangulated genus zero surfaces representing the protein and
      the round sphere, respectively, and constructs a discrete conformal map f between
      these surfaces. The conformal map is chosen to minimize a symmetric elastic
      energy E S (f) that measures the distance of f from an isometry. We illustrate
      our approach on a set of basic sample problems and then on a dataset of diverse
      protein structures. We show first that E S (f) is able to quantify the roundness
      of the Platonic solids and that for these surfaces it replicates well traditional
      measures of roundness such as the sphericity. We then demonstrate that the
      symmetric elastic energy E S (f) captures both global and local differences
      between two surfaces, showing that our method identifies the presence of
      protruding regions in protein structures and quantifies how these regions make
      the shape of a protein deviate from globularity. Based on these results, we show
      that E S (f) serves as a probe of the limits of the application of conformal
      mapping to parametrize protein shapes. We identify limitations of the method and
      discuss its extension to achieving automatic registration of protein structures
      based on their surface geometry. 

PMID- 25988169
TI  - DNA studies using atomic force microscopy: capabilities for measurement of short
      DNA fragments.
AB  - Short DNA fragments, resulting from ionizing radiation induced DNA double strand
      breaks (DSBs), or released from cells as a result of physiological processes and
      circulating in the blood stream, may play important roles in cellular function
      and potentially in disease diagnosis and early intervention. The size
      distribution of DNA fragments contribute to knowledge of underlining biological
      processes. Traditional techniques used in radiation biology for DNA fragment size
      measurements lack the resolution to quantify short DNA fragments. For the
      measurement of cell-free circulating DNA (ccfDNA), real time quantitative
      Polymerase Chain Reaction (q-PCR) provides quantification of DNA fragment sizes,
      concentration and specific gene mutation. A complementary approach, the imaging
      based technique using Atomic Force Microscopy (AFM) provides direct visualization
      and measurement of individual DNA fragments. In this review, we summarize and
      discuss the application of AFM-based measurements of DNA fragment sizes. Imaging
      of broken plasmid DNA, as a result of exposure to ionizing radiation, as well as
      ccfDNA in clinical specimens offer an innovative approach for studies of short
      DNA fragments and their biological functions. 

PMID- 25988168
TI  - Ser or Leu: structural snapshots of mistranslation in Candida albicans.
AB  - Candida albicans is a polymorphic opportunistic fungal pathogen normally residing
      as commensal on mucosal surfaces, skin and gastrointestinal and genitourinary
      tracts. However, in immunocompromised patients C. albicans can cause superficial
      mucosal infections or life-threatening disseminated candidemia. A change in
      physiological conditions triggers a cascade of molecular events leading to
      morphogenetic alterations and increased resistance to damage induced by host
      defenses. The complex biology of this human pathogen is reflected in its
      morphological plasticity and reinforced by the ability to ambiguously translate
      the universal leucine CUG codon predominantly as serine, but also as leucine.
      Mistranslation affects more than half of C. albicans proteome and it is
      widespread across many biological processes. A previous analysis of CTG-codon
      containing gene products in C. albicans suggested that codon ambiguity subtly
      shapes protein function and might have a pivotal role in signaling cascades
      associated with morphological changes and pathogenesis. In this review we further
      explore this hypothesis by highlighting the role of ambiguous decoding in
      macromolecular recognition of key effector proteins associated with the
      regulation of signal transduction cascades and the cell cycle, which are critical
      processes for C. albicans morphogenic plasticity under a variety of environmental
      conditions. 

PMID- 25988170
TI  - Allosteric regulation of deubiquitylase activity through ubiquitination.
AB  - Ataxin-3, the protein responsible for spinocerebellar ataxia type-3, is a
      cysteine protease that specifically cleaves poly-ubiquitin chains and
      participates in the ubiquitin proteasome pathway. The enzymatic activity resides
      in the N-terminal Josephin domain. An unusual feature of ataxin-3 is its low
      enzymatic activity especially for mono-ubiquitinated substrates and short
      ubiquitin chains. However, specific ubiquitination at lysine 117 in the Josephin
      domain activates ataxin-3 through an unknown mechanism. Here, we investigate the
      effects of K117 ubiquitination on the structure and enzymatic activity of the
      protein. We show that covalently linked ubiquitin rests on the Josephin domain,
      forming a compact globular moiety and occupying a ubiquitin binding site
      previously thought to be essential for substrate recognition. In doing so,
      ubiquitination enhances enzymatic activity by locking the enzyme in an activated
      state. Our results indicate that ubiquitin functions both as a substrate and as
      an allosteric regulatory factor. We provide a novel example in which a
      conformational switch controls the activity of an enzyme that mediates
      deubiquitination. 

PMID- 25988171
TI  - Mediation of organismal aging and somatic proteostasis by the germline.
AB  - Experimental interventions that reduce reproduction cause an extension in
      lifespan. In invertebrates, such as Caenorhabditis elegans, the aging of the soma
      is regulated by signals from the germline. Indeed, ablation of germ cells
      significantly extends lifespan. Notably, germline-deficient animals exhibit
      heightened resistance to proteotoxic stress. This phenotype correlates with
      increased potential of intracellular clearance mechanisms such as the proteasome
      and autophagy in somatic tissues. Here we review the molecular mechanisms by
      which signals from the germline regulate lifespan in C. elegans with special
      emphasis on clearance mechanisms. 

PMID- 25988172
TI  - A data preprocessing strategy for metabolomics to reduce the mask effect in data
      analysis.
AB  - HighlightsDeveloped a data preprocessing strategy to cope with missing values and
      mask effects in data analysis from high variation of abundant metabolites.A new
      method- 'x-VAST' was developed to amend the measurement deviation
      enlargement.Applying the above strategy, several low abundant masked differential
      metabolites were rescued. Metabolomics is a booming research field. Its success
      highly relies on the discovery of differential metabolites by comparing different
      data sets (for example, patients vs. controls). One of the challenges is that
      differences of the low abundant metabolites between groups are often masked by
      the high variation of abundant metabolites. In order to solve this challenge, a
      novel data preprocessing strategy consisting of three steps was proposed in this
      study. In step 1, a 'modified 80%' rule was used to reduce effect of missing
      values; in step 2, unit-variance and Pareto scaling methods were used to reduce
      the mask effect from the abundant metabolites. In step 3, in order to fix the
      adverse effect of scaling, stability information of the variables deduced from
      intensity information and the class information, was used to assign suitable
      weights to the variables. When applying to an LC/MS based metabolomics dataset
      from chronic hepatitis B patients study and two simulated datasets, the mask
      effect was found to be partially eliminated and several new low abundant
      differential metabolites were rescued. 

PMID- 25988174
TI  - Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium
      tuberculosis.
AB  - Comparison of genome sequences from clinical isolates of Mycobacterium
      tuberculosis with phylogenetically-related pathogens Mycobacterium marinum,
      Mycobacterium kansasii, and Mycobacterium leprae reveals diversity amongst genes
      associated with vitamin B12-related metabolism. Diversity is generated by gene
      deletion events, differential acquisition of genes by horizontal transfer, and
      single nucleotide polymorphisms (SNPs) with predicted impact on protein function
      and transcriptional regulation. Differences in the B12 synthesis pathway,
      methionine biosynthesis, fatty acid catabolism, and DNA repair and replication
      are consistent with adaptations to different environmental niches and pathogenic
      lifestyles. While there is no evidence of further gene acquisition during
      expansion of the M. tuberculosis complex, the emergence of other forms of genetic
      diversity provides insights into continuing host-pathogen co-evolution and has
      the potential to identify novel targets for disease intervention. 

PMID- 25988173
TI  - On the energy components governing molecular recognition in the framework of
      continuum approaches.
AB  - Molecular recognition is a process that brings together several biological
      macromolecules to form a complex and one of the most important characteristics of
      the process is the binding free energy. Various approaches exist to model the
      binding free energy, provided the knowledge of the 3D structures of bound and
      unbound molecules. Among them, continuum approaches are quite appealing due to
      their computational efficiency while at the same time providing predictions with
      reasonable accuracy. Here we review recent developments in the field emphasizing
      on the importance of adopting adequate description of physical processes taking
      place upon the binding. In particular, we focus on the efforts aiming at
      capturing some of the atomistic details of the binding phenomena into the
      continuum framework. When possible, the energy components are reviewed
      independently of each other. However, it is pointed out that rigorous approaches
      should consider all energy contributions on the same footage. The two major
      schemes for utilizing the individual energy components to predict binding
      affinity are outlined as well. 

PMID- 25988175
TI  - Pyroglutamyl-N-terminal prion protein fragments in sheep brain following the
      development of transmissible spongiform encephalopathies.
AB  - Protein misfolding, protein aggregation and disruption to cellular proteostasis
      are key processes in the propagation of disease and, in some progressive
      neurodegenerative diseases of the central nervous system, the misfolded protein
      can act as a self-replicating template or prion converting its normal isoform
      into a misfolded copy of itself. We have investigated the sheep transmissible
      spongiform encephalopathy, scrapie, and developed a multiple selected reaction
      monitoring (mSRM) mass spectrometry assay to quantify brain peptides representing
      the "ragged" N-terminus and the core of ovine prion protein (PrP(Sc)) by using Q
      Tof mass spectrometry. This allowed us to identify pyroglutamylated N-terminal
      fragments of PrP(Sc) at residues 86, 95 and 101, and establish that these
      fragments were likely to be the result of in vivo processes. We found that the
      ratios of pyroglutamylated PrP(Sc) fragments were different in sheep of different
      breeds and geographical origin, and our expanded ovine PrP(Sc) assay was able to
      determine the ratio and allotypes of PrP accumulating in diseased brain of PrP
      heterozygous sheep; it also revealed significant differences between N-terminal
      amino acid profiles (N-TAAPs) in other types of ovine prion disease, CH1641
      scrapie and ovine BSE. Variable rates of PrP misfolding, aggregation and
      degradation are the likely basis for phenotypic (or strain) differences in prion
      affected animals and our mass spectrometry-based approach allows the simultaneous
      investigation of factors such as post-translational modification (pyroglutamyl
      formation), conformation (by N-TAAP analysis) and amino-acid polymorphisms
      (allotype ratio) which affect the kinetics of these proteostatic processes. 

PMID- 25988176
TI  - Quantifying the role of chaperones in protein translocation by computational
      modeling.
AB  - The molecular chaperone Hsp70 plays a central role in the import of cytoplasmic
      proteins into organelles, driving their translocation by binding them from the
      organellar interior. Starting from the experimentally-determined structure of the
      E. coli Hsp70, we computed, by means of molecular simulations, the effective free
      energy profile for substrate translocation upon chaperone binding. We then used
      the resulting free energy to quantitatively characterize the kinetics of the
      import process, whose comparison with unassisted translocation highlights the
      essential role played by Hsp70 in importing cytoplasmic proteins. 

PMID- 25988177
TI  - Using docking and alchemical free energy approach to determine the binding
      mechanism of eEF2K inhibitors and prioritizing the compound synthesis.
AB  - A-484954 is a known eEF2K inhibitor with submicromolar IC50 potency. However, the
      binding mechanism and the crystal structure of the kinase remains unknown. Here,
      we employ a homology eEF2K model, docking and alchemical free energy simulations
      to probe the binding mechanism of eEF2K, and in turn, guide the optimization of
      potential lead compounds. The inhibitor was docked into the ATP-binding site of a
      homology model first. Three different binding poses, hypothesis 1, 2, and 3, were
      obtained and subsequently applied to molecular dynamics (MD) based alchemical
      free energy simulations. The calculated relative binding free energy of the
      analogs of A-484954 using the binding pose of hypothesis 1 show a good
      correlation with the experimental IC50 values, yielding an r (2) coefficient of
      0.96 after removing an outlier (compound 5). Calculations using another two poses
      show little correlation with experimental data, (r (2) of less than 0.5 with or
      without removing any outliers). Based on hypothesis 1, the calculated relative
      free energy suggests that bigger cyclic groups, at R1 e.g., cyclobutyl and
      cyclopentyl promote more favorable binding than smaller groups, such as
      cyclopropyl and hydrogen. Moreover, this study also demonstrates the ability of
      the alchemical free energy approach in combination with docking and homology
      modeling to prioritize compound synthesis. This can be an effective means of
      facilitating structure-based drug design when crystal structures are not
      available. 

PMID- 25988178
TI  - Check and mate to exosomal extracellular miRNA: new lesson from a new approach.
AB  - MicroRNAs (miRNAs) are 19-24 nt single-stranded RNAs which regulate gene
      expression by sequence-specific targeting of corresponding mRNAs. Extracellular
      miRNAs have been consistently detected in all human body fluids, and were shown
      to be prominent non-invasive biomarkers for various diseases including cancer.
      Albeit biological function of cell-free miRNA remains questionable, some studies
      demonstrated that exosomes encapsulated extracellular miRNAs could mediate inter
      cellular signaling. While others suggested that these miRNAs are mostly by
      products of cellular activity and do not carry any significant biological
      function. This article aims to discuss the current theories of origin of
      extracellular miRNA, and to highlight recent application of a novel technique of
      micro-vesicles counting, that may challenge the existence of exosomal miRNA. 

PMID- 25988181
TI  - Alternative salt bridge formation in Abeta-a hallmark of early-onset Alzheimer's
      disease?
AB  - Recently the 3D structure of the Osaka mutant form (E22Delta) of Amyloid-beta1-40
      has been determined. We here compare the NMR chemical-shift with the published
      shifts of a brain-seeded form of wild-type Abeta and suggest that the determined
      mutant fold is accessible to the wild-type protein as well, with small
      conformational adaptations which accommodate the E22 residue missing in the Osaka
      mutant. In addition, we illustrate how other mutants could also conform to this
      model. The stabilization of the N-terminal part of the protein via an
      intermolecular salt bridge to Lys28 may represent a common structural motif for
      the mutants which are related to early-onset Alzheimer disease. This feature
      might connect to the observed increased toxicity of the mutant forms compared to
      wild-type Abeta1-40, where the salt bridge involving Lys28 is intramolecular. 

PMID- 25988180
TI  - Methylation of cell-free circulating DNA in the diagnosis of cancer.
AB  - A range of molecular alterations found in tumor cells, such as DNA mutations and
      DNA methylation, is reflected in cell-free circulating DNA (circDNA) released
      from the tumor into the blood, thereby making circDNA an ideal candidate for the
      basis of a blood-based cancer diagnosis test. In many cancer types, mutations
      driving tumor development and progression are present in a wide range of
      oncogenes and tumor suppressor genes. However, even when a gene is consistently
      mutated in a particular cancer, the mutations can be spread over very large
      regions of its sequence, making evaluation difficult. This diversity of sequence
      changes in tumor DNA presents a challenge for the development of blood tests
      based on DNA mutations for cancer diagnosis. Unlike mutations, DNA methylation
      that can be consistently measured, as it tends to occur in specific regions of
      the DNA called CpG islands. Since DNA methylation is reflected within circDNA,
      detection of tumor-specific DNA methylation in patient plasma is a feasible
      approach for the development of a blood-based test. Aberrant circDNA methylation
      has been described in most cancer types and is actively being investigated for
      clinical applications. A commercial blood test for colorectal cancer based on the
      methylation of the SEPT9 promoter region in circDNA is under review for approval
      by the Federal Drug Administration (FDA) for clinical use. In this paper, we
      review the state of research in circDNA methylation as an application for blood
      based diagnostic tests in colorectal, breast, lung, pancreatic and ovarian
      cancers, and we consider some of the future directions and challenges in this
      field. There are a number of potential circDNA biomarkers currently under
      investigation, and experience with SEPT9 shows that the time to clinical
      translation can be relatively rapid, supporting the promise of circDNA as a
      biomarker. 

PMID- 25988179
TI  - From protein structure to function via single crystal optical spectroscopy.
AB  - The more than 100,000 protein structures determined by X-ray crystallography
      provide a wealth of information for the characterization of biological processes
      at the molecular level. However, several crystallographic "artifacts," including
      conformational selection, crystallization conditions and radiation damages, may
      affect the quality and the interpretation of the electron density maps, thus
      limiting the relevance of structure determinations. Moreover, for most of these
      structures, no functional data have been obtained in the crystalline state, thus
      posing serious questions on their validity in infereing protein mechanisms. In
      order to solve these issues, spectroscopic methods have been applied for the
      determination of equilibrium and kinetic properties of proteins in the
      crystalline state. These methods are UV-vis spectrophotometry,
      spectrofluorimetry, IR, EPR, Raman, and resonance Raman spectroscopy. Some of
      these approaches have been implemented with on-line instruments at X-ray
      synchrotron beamlines. Here, we provide an overview of investigations
      predominantly carried out in our laboratory by single crystal polarized
      absorption UV-vis microspectrophotometry, the most applied technique for the
      functional characterization of proteins in the crystalline state. Studies on
      hemoglobins, pyridoxal 5'-phosphate dependent enzymes and green fluorescent
      protein in the crystalline state have addressed key biological issues, leading to
      either straightforward structure-function correlations or limitations to
      structure-based mechanisms. 

PMID- 25988182
TI  - Anti-adaptors use distinct modes of binding to inhibit the RssB-dependent
      turnover of RpoS (sigma(S)) by ClpXP.
AB  - In Escherichia coli, sigma(S) is the master regulator of the general stress
      response. The level of sigma(S) changes in response to multiple stress conditions
      and it is regulated at many levels including protein turnover. In the absence of
      stress, sigma(S) is rapidly degraded by the AAA+ protease, ClpXP in a regulated
      manner that depends on the adaptor protein RssB. This two-component response
      regulator mediates the recognition of sigma(S) and its delivery to ClpXP. The
      turnover of sigma(S) however, can be inhibited in a stress specific manner, by
      one of three anti-adaptor proteins. Each anti-adaptor binds to RssB and inhibits
      its activity, but how this is achieved is not fully understood at a molecular
      level. Here, we describe details of the interaction between each anti-adaptor and
      RssB that leads to the stabilization of sigma(S). By defining the domains of RssB
      using partial proteolysis we demonstrate that each anti-adaptor uses a distinct
      mode of binding to inhibit RssB activity. IraD docks specifically to the N
      terminal domain of RssB, IraP interacts primarily with the C-terminal domain,
      while IraM interacts with both domains. Despite these differences in binding, we
      propose that docking of each anti-adaptor induces a conformational change in
      RssB, which resembles the inactive dimer of RssB. This dimer-like state of RssB
      not only prevents substrate binding but also triggers substrate release from a
      pre-bound complex. 

PMID- 25988184
TI  - The AAA+ proteins Pontin and Reptin enter adult age: from understanding their
      basic biology to the identification of selective inhibitors.
AB  - Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases
      Associated with various cellular Activities) family. They are implicated in
      multiple and seemingly unrelated processes encompassing the regulation of gene
      transcription, the remodeling of chromatin, DNA damage sensing and repair, and
      the assembly of protein and ribonucleoprotein complexes, among others. The 2nd
      International Workshop on Pontin and Reptin took place at the Instituto de
      Tecnologia Quimica e Biologica Antonio Xavier in Oeiras, Portugal on October 10
      12, 2014, and reported significant new advances on the mechanisms of action of
      these two AAA+ ATPases. The major points under discussion were related to the
      mechanisms through which these proteins regulate gene transcription, their roles
      as co-chaperones, and their involvement in pathophysiology, especially in cancer
      and ciliary biology and disease. Finally, they may become anticancer drug targets
      since small chemical inhibitors were shown to produce anti-tumor effects in
      animal models. 

PMID- 25988186
TI  - Multifaceted role of matrix metalloproteinases (MMPs).
AB  - Matrix metalloproteinases (MMPs), a large family of calcium-dependent zinc
      containing endopeptidases, are involved in the tissue remodeling and degradation
      of the extracellular matrix. MMPs are widely distributed in the brain and
      regulate various processes including microglial activation, inflammation,
      dopaminergic apoptosis, blood-brain barrier disruption, and modulation of alpha
      synuclein pathology. High expression of MMPs is well documented in various
      neurological disorders including Parkinson's disease (PD), Alzheimer's disease
      (AD), Japanese encephalitis (JE), and Glaucoma. Although potentially critical,
      the role of MMPs in neuronal disorders is under-investigated. The present review
      summarizes the role of MMPs in neurodegeneration with a particular emphasis on
      PD, AD, JE, and Glaucoma. 

PMID- 25988187
TI  - Integrating Patient-Reported Outcomes into Spine Surgical Care through Visual
      Dashboards: Lessons Learned from Human-Centered Design.
AB  - INTRODUCTION: The collection of patient-reported outcomes (PROs) draws attention
      to issues of importance to patients-physical function and quality of life. The
      integration of PRO data into clinical decisions and discussions with patients
      requires thoughtful design of user-friendly interfaces that consider user
      experience and present data in personalized ways to enhance patient care. Whereas
      most prior work on PROs focuses on capturing data from patients, little research
      details how to design effective user interfaces that facilitate use of this data
      in clinical practice. We share lessons learned from engaging health care
      professionals to inform design of visual dashboards, an emerging type of health
      information technology (HIT). METHODS: We employed human-centered design (HCD)
      methods to create visual displays of PROs to support patient care and quality
      improvement. HCD aims to optimize the design of interactive systems through
      iterative input from representative users who are likely to use the system in the
      future. Through three major steps, we engaged health care professionals in
      targeted, iterative design activities to inform the development of a PRO
      Dashboard that visually displays patient-reported pain and disability outcomes
      following spine surgery. FINDINGS: Design activities to engage health care
      administrators, providers, and staff guided our work from design concept to
      specifications for dashboard implementation. Stakeholder feedback from these
      health care professionals shaped user interface design features, including
      predefined overviews that illustrate at-a-glance trends and quarterly snapshots,
      granular data filters that enable users to dive into detailed PRO analytics, and
      user-defined views to share and reuse. Feedback also revealed important
      considerations for quality indicators and privacy-preserving sharing and use of
      PROs. CONCLUSION: Our work illustrates a range of engagement methods guided by
      human-centered principles and design recommendations for optimizing PRO
      Dashboards for patient care and quality improvement. Engaging health care
      professionals as stakeholders is a critical step toward the design of user
      friendly HIT that is accepted, usable, and has the potential to enhance quality
      of care and patient outcomes.

PMID- 25988183
TI  - Elements of the cellular metabolic structure.
AB  - A large number of studies have demonstrated the existence of metabolic covalent
      modifications in different molecular structures, which are able to store
      biochemical information that is not encoded by DNA. Some of these covalent mark
      patterns can be transmitted across generations (epigenetic changes). Recently,
      the emergence of Hopfield-like attractor dynamics has been observed in self
      organized enzymatic networks, which have the capacity to store functional
      catalytic patterns that can be correctly recovered by specific input stimuli.
      Hopfield-like metabolic dynamics are stable and can be maintained as a long-term
      biochemical memory. In addition, specific molecular information can be
      transferred from the functional dynamics of the metabolic networks to the
      enzymatic activity involved in covalent post-translational modulation, so that
      determined functional memory can be embedded in multiple stable molecular marks.
      The metabolic dynamics governed by Hopfield-type attractors (functional
      processes), as well as the enzymatic covalent modifications of specific molecules
      (structural dynamic processes) seem to represent the two stages of the dynamical
      memory of cellular metabolism (metabolic memory). Epigenetic processes appear to
      be the structural manifestation of this cellular metabolic memory. Here, a new
      framework for molecular information storage in the cell is presented, which is
      characterized by two functionally and molecularly interrelated systems: a
      dynamic, flexible and adaptive system (metabolic memory) and an essentially
      conservative system (genetic memory). The molecular information of both systems
      seems to coordinate the physiological development of the whole cell. 

PMID- 25988185
TI  - LOV-based optogenetic devices: light-driven modules to impart photoregulated
      control of cellular signaling.
AB  - The Light-Oxygen-Voltage domain family of proteins is widespread in biology where
      they impart sensory responses to signal transduction domains. The small, light
      responsive LOV modules offer a novel platform for the construction of optogenetic
      tools. Currently, the design and implementation of these devices is partially
      hindered by a lack of understanding of how light drives allosteric changes in
      protein conformation to activate diverse signal transduction domains. Further,
      divergent photocycle properties amongst LOV family members complicate
      construction of highly sensitive devices with fast on/off kinetics. In the
      present review we discuss the history of LOV domain research with primary
      emphasis on tuning LOV domain chemistry and signal transduction to allow for
      improved optogenetic tools. 

PMID- 25988188
TI  - Anti-CD28 Antibody-Initiated Cytokine Storm in Canines.
AB  - BACKGROUND: CD28 signal blockade following T cell receptor activation is under
      intense investigation as a tolerance-inducing therapy for transplantation. Our
      goal is to produce a CD28-specific reagent as a therapy for the prevention of
      graft rejection and graft-versus-host disease in the canine model of allogeneic
      hematopoietic cell transplantation (HCT). METHODS: We infused a monoclonal mouse
      anti-canine CD28 antibody (1C6 mAb) into four dogs and a fragment of antigen
      binding (1C6 Fab) into two dogs. Pharmacokinetics, pathology, cytokine release,
      and the crystal structure of 1C6 Fv were evaluated. RESULTS: Within an hour of an
      IV injection of the 1C6 mAb, the dogs became leukopenic and developed a steroid
      refractory cytokine storm. Two of the dogs developed high fevers, one experienced
      diffuse alveolar hemorrhage, and another developed gastrointestinal hemorrhage.
      The cytokine storm was characterized by elevated plasma levels of MCP-1, IP-10,
      IL-10, IL-6, and TNF-alpha. In addition, one dog showed elevated levels of IL-2,
      IL-8, and IL-18. In contrast, infusion of 1C6 Fab was well tolerated without any
      side effects. Dry-coating 1C6 mAb onto tissue culture plates induced CD3
      independent proliferation and TNF-alpha production. Crystal structure analysis
      revealed that 1C6 binds to canine CD28 in a manner different than previously
      reported for conventional agonistic or superagonistic antibodies. CONCLUSIONS:
      These results indicate that dogs and humans develop a similar cytokine storm
      following infusion ofanti-CD28 mAb, providing an appropriate large animal for
      further study. 1C6 Fab warrants evaluation as a tolerance-inducing reagent in the
      canine model of allogeneic HCT.

PMID- 25988189
TI  - Integrated miRNA and mRNA Analysis of Time Series Microarray Data.
AB  - The dynamic temporal regulatory effects of microRNA are not well known. We
      introduce a technique for integrating miRNA and mRNA time series microarray data
      with known disease pathology. The integrated analysis includes identifying both
      mRNA and miRNA that are signi cantly similar to the quantitative pathology.
      Potential regulatory miRNA/mRNA target pairs are identi ed through databases of
      both predicted and validated pairs. Finally, potential target pairs are ltered by
      examining the second derivatives of the fold changes over time. Our system was
      used on genome-wide microarray expression data of mouse lungs (n = 160) following
      aspiration of multi-walled carbon nanotubes. This system shows promise of readily
      identifying miRNA for further study as potential biomarker use.

PMID- 25988190
TI  - Periodontal risk and recall interval evaluation after a program of comprehensive
      supragingival plaque control.
AB  - OBJECTIVE: To investigate if a comprehensive supragingival control can modify the
      periodontal risk and suggested recall interval over time, using an adaptation of
      an available model of periodontal risk assessment (PRA, Perio-Tools(r) website).
      METHOD AND MATERIALS: Single-arm clinical trial data (visible plaque and gingival
      bleeding indexes, periodontal probing depth, bleeding on probing, and clinical
      attachment level from baseline (day 0, T0), day 30 (T1), and day 180 (T2) from 50
      moderate-to-severe periodontitis patients (25 never-smokers; 25 smokers)
      submitted to a comprehensive supragingival plaque control regimen for 180 days
      were subjected to a secondary analysis using an adaptation of the PRA. The
      periodontal risk (high, medium, or low) and suggested recall interval were
      calculated per patient and at each experimental time. General linear models and
      the Cochran test were used for statistical analysis, considering the dependence
      of the data. RESULTS: All patients were at high risk at baseline. At T1, 20%
      migrated to medium-risk (P = .002). At T2, 38% and 8% exhibited medium- and low
      risk, respectively (P <= .001). The reduction between T1 and T2 was significant
      (P = .001). The mean recall interval increased from 3.0 +/- 0.0 (T0) to 3.6 +/-
      1.2 (T1), and 4.9 +/- 2.6 months at T2 (P < .003). The effect that smoking habit
      exerted on risk was limited to the first 30 days, and no effect on recall
      interval was observed. CONCLUSION: The oral hygiene condition is an important
      indicator that influences the risk and the recall interval over time, thus
      deserving attention when evaluating the individual periodontal prognosis.

PMID- 25988191
TI  - Three-dimensional finite element analysis of stress distribution of two-retainer
      and single-retainer all-ceramic resin-bonded fixed partial dentures.
AB  - OBJECTIVE: A long-term clinical study previously stated that adhesively luted
      resin-bonded fixed partial dentures (RBFPDs) with two retainers exhibited two
      complications (loss of adhesion or fracture between retainer and pontic) when
      compared to RBFPDs with a single retainer. The reasons for these complications
      were not reported. The aim of this study was to evaluate the stress distribution
      of two-retainer and singleretainer zirconium dioxide RBFPDs by using three
      dimensional finite element analysis (3D FEA). METHOD AND MATERIALS: Two different
      3D finite element models were created. Each model contained cortical bone,
      cancellous bone, periodontal ligament, cement, and enamel. Additionally one of
      the models contained a two-retainer zirconium dioxide RBFPD while another
      contained a single-retainer zirconium dioxide RBFPD. A 100 N force was applied at
      45 degrees 2 mm below the incisal edge of the palatal surface of the pontic. In
      each model, Von Mises stress distribution was evaluated. RESULTS: Maximum Von
      Mises stress values in RBFPD with a single retainer and two retainers were 1.13
      MPa and 1.23 MPa, respectively. Von Mises stress was concentrated at the
      interface between pontic and retainer for RBFPD with two retainers. CONCLUSION:
      Zirconium dioxide RBFPD with a single retainer and two retainers exhibited
      similar stress concentrations between pontic and retainer. However, the use of a
      single retainer for RBFPDs prevented stress concentration at the interface
      between retainer and pontic.

PMID- 25988192
TI  - GBR using cross-linked collagen membrane and a new highly purified bovine
      xenograft (Laddec) in horizontal ridge augmentation: Case report of clinical and
      histomorphometric analysis.
AB  - This case report presents the clinical and histologic evaluation of the
      application of a cross-linked collagen membrane and a new highly purified bovine
      xenograft with type 1 collagen fiber preservation (Laddec) in mandibular
      horizontal ridge augmentation on a 50-year-old woman. Significant bone volume was
      achieved to restore severe bone defect in order to place two implants.
      Histomorphometric analysis of a bone core at the augmented site, at 6 months,
      showed new bone formation with bone substitute particles integrated to new viable
      bone. 

PMID- 25988193
TI  - Report on the clinical technique of thermo-curing glass-ionomer sealant.
AB  - Controversy exists regarding the general safety of resin sealants and in
      particular their use in children, due to the possible leaching of non-polymerized
      monomers including bisphenol A. A thermally cured high-viscosity glass-ionomer
      cement (GIC) is suggested as a first-choice sealant material. An innovative
      approach of thermo-curing the GIC during placement is presented. The step-by-step
      clinical procedure and rationale for the biomimetic thermo-cured glass-ionomer
      fissure sealant are introduced and described. A thermally cured GIC sealant may
      provide long-term caries protection to fissures and pits without the need to
      maintain and reseal. GICs are both biocompatible and biomimetic resulting in
      formation of fluorapatite, the ultimate protection against dental caries. 

PMID- 25988194
TI  - Effects of electric fields on human mesenchymal stem cell behaviour and
      morphology using a novel multichannel device.
AB  - The intrinsic piezoelectric nature of collagenous-rich tissues, such as bone and
      cartilage, can result in the production of small, endogenous electric fields
      (EFs) during applied mechanical stresses. In vivo, these EFs may influence cell
      migration, a vital component of wound healing. As a result, the application of
      small external EFs to bone fractures and cutaneous wounds is actively practiced
      clinically. Due to the significant regenerative potential of stem cells in bone
      and cartilage healing, and their potential role in the observed improved healing
      in vivo post applied EFs, using a novel medium throughput device, we investigated
      the impacts of physiological and aphysiological EFs on human bone marrow-derived
      mesenchymal stem cells (hBM-MSCs) for up to 15 hours. The applied EFs had
      significant impacts on hBM-MSC morphology and migration; cells displayed varying
      degrees of conversion to a highly elongated phenotype dependent on the EF
      strength, consistent perpendicular alignment to the EF vector, and definitive
      cathodal migration in response to EF strengths >=0.5 V cm(-1), with the fastest
      migration speeds observed at between 1.7 and 3 V cm(-1). We observed variability
      in hBM-MSC donor-to-donor responses and overall tolerances to applied EFs. This
      study thus confirms hBM-MSCs are responsive to applied EFs, and their rate of
      migration towards the cathode is controllable depending on the EF strength,
      providing new insight into the physiology of hBM-MSCs and possibly a significant
      opportunity for the utilisation of EFs in directed scaffold colonisation in vitro
      for tissue engineering applications or in vivo post implantation. 

PMID- 25988195
TI  - Unsupervised explorative data analysis of normal human leukocytes and BCR/ABL
      positive leukemic cells mid-infrared spectra.
AB  - We proved the ability of Fourier Transform Infrared microspectroscopy (microFTIR)
      complemented by Principal Component Analysis (PCA) to detect protein
      phosphorylation/de-phosphorylation in mammalian cells. We analyzed by microFTIR
      human polymorphonuclear neutrophil (PMNs) leukocytes, mouse-derived parental
      Ba/F3 cells (Ba/F3#PAR), Ba/F3 cells transfected with p210(BCR/ABL) (Ba/F3#WT)
      and expressing high levels of protein tyrosine kinase (PTK), and human-derived
      BCR/ABL positive K562 leukemic cell sub-clones engineered to differently express
      receptor-type tyrosine-protein phosphatase gamma (PTPRG). Synchrotron radiation
      (SR) and conventional (globar) IR sources were used to perform microFTIR
      respectively, on single cells and over several cells within the same sample. Ex
      vivo time-course experiments were run, inducing maximal protein phosphorylation
      in PMNs by 100 nM N-formylated tripeptide fMLP. Within the specific IR
      fingerprint 1800-850 cm(-1) frequency domain, PCA identified two regions with
      maximal signal variance. These were used to model and test the robustness of PCA
      in representing the dynamics of protein phosphorylation/de-phosphorylation
      processes. An IR signal ratio marker reflecting the homeostatic control by
      protein kinases and phosphatases was identified in normal leukocytes. The models
      identified by microFTIR and PCA in normal leukocytes also distinguished BCR/ABL
      positive Ba/F3#WT from BCR/ABL negative Ba/F3#PAR cells as well as K562 cells
      exposed to functionally active protein tyrosine phosphatase recombinant protein
      ICD-Tat transduced in cells by HIV-1 Tat technology or cells treated with the PTK
      inhibitor imatinib mesylate (IMA) from cells exposed to phosphatase inactive
      (D1028A)ICD-Tat recombinant protein and untreated control cells, respectively.
      The IR signal marker correctly reflected the degrees of protein phosphorylation
      associated with abnormal PTK activity in BCR/ABL positive leukemic cells and in
      general was inversely related to the expression/activity of PTPRG in leukemic sub
      clones. In conclusion, we have described a new, reliable and simple spectroscopic
      method to study the ex vivo protein phosphorylation/de-phosphorylation balance in
      cell models: it is suitable for biomedical and pharmacological research labs but
      it also needs further optimization and its evaluation on large cohorts of
      patients to be proposed in the clinical setting of leukemia. 

PMID- 25988196
TI  - Detection of trace heavy metal ions in water by nanostructured porous Si
      biosensors.
AB  - A generic biosensing platform, based on nanostructured porous Si (PSi), Fabry
      Perot thin films, for label-free monitoring of heavy metal ions in aqueous
      solutions by enzymatic activity inhibition, is described. First, we show a
      general detection assay by immobilizing horseradish peroxidase (HRP) within the
      oxidized PSi nanostructure and monitor its catalytic activity in real time by
      reflective interferometric Fourier transform spectroscopy. Optical studies reveal
      the high specificity and sensitivity of the HRP-immobilized PSi towards three
      metal ions (Ag(+) > Pb(2+) > Cu(2+)), with a detection limit range of 60-120 ppb.
      Next, we demonstrate the concept of specific detection of Cu(2+) ions (as a model
      heavy metal) by immobilizing Laccase, a multi-copper oxidase, within the oxidized
      PSi. The resulting biosensor allows for specific detection and quantification of
      copper ions in real water samples by monitoring the Laccase relative activity.
      The optical biosensing results are found to be in excellent agreement with those
      obtained by the gold standard analytical technique (ICP-AES) for all water
      samples. The main advantage of the presented biosensing concept is the ability to
      detect heavy metal ions at environmentally relevant concentrations using a simple
      and portable experimental setup, while the specific biosensor design can be
      tailored by varying the enzyme type. 

PMID- 25988197
TI  - A microfluidic immunoassay platform for the detection of free prostate specific
      antigen: a systematic and quantitative approach.
AB  - As a leading cause of cancer-related deaths in men globally, prostate cancer
      (PCa) demands immense attention for theranostic purposes. There is an increasing
      need for the development of rapid, sensitive, economical, miniaturized and
      multiplexable assays. Towards this goal, we present a systematic approach for the
      optimisation of a microfluidic sandwich immunoassay, which can be applied as a
      generic biosensor platform for PCa detection. Prostate specific antigen (PSA) was
      used as the model biomarker, and its free form was captured using commercially
      available antibodies and detected using chemiluminescence, both in spiked buffer
      and matrix solutions. Along with the optimisation of surface chemistry and
      microfluidic parameters, we report a bio-affinity amplification strategy based on
      biotin-streptavidin chemistry to bring the limits of detection for free-PSA from
      21.4 ng mL(-1) down to 2.7 ng mL(-1), within the clinically relevant range. An
      estimate of the surface coverage and simulations of the interactions taking place
      in the microfluidic biosensor during the assay are also presented. This novel
      platform using a simple passive adsorption-based bio-affinity strategy, when
      coupled with multiplexing and integrated detection, can serve as a promising
      point-of-care diagnostic tool for PCa. 

PMID- 25988199
TI  - Sensitive colorimetric detection of protein by gold nanoparticles and rolling
      circle amplification.
AB  - An ultrasensitive method for the detection of protein is critically important in
      fundamental research and practical applications due to the low abundance of
      disease markers in body fluids or tissues. To detect the trace levels of disease
      markers with high sensitivity and specificity, a sensitive colorimetric biosensor
      for protein assay was developed using gold nanoparticles (AuNPs) and rolling
      circle amplification (RCA). After binding the biotinylated primer/circular
      template to the streptavidin-conjugated sandwich ELISA immunocomplex, the
      biotinylated primer was isothermally extended to generate single-stranded DNA
      (ssDNA). Sequentially, the padlock DNA was added and hybridized with the RCA
      products. The aggregation of the additional AuNPs in the supernatant containing
      the surplus padlock DNA and a certain concentration of salt could then be
      observed. The established sensor allowed for the specific detection of alpha
      fetoprotein (AFP) with a detection limit of 33.45 pg mL(-1). It was also
      demonstrated that this method could distinguish 500 pg mL(-1) AFP with the naked
      eye. In addition, this biosensor could be applied to complex sample analysis and
      could be further used as a universal method for any protein or virus
      determination by changing the corresponding antibodies. 

PMID- 25988198
TI  - A cationic fluorescent polymeric thermometer for the ratiometric sensing of
      intracellular temperature.
AB  - We developed new cationic fluorescent polymeric thermometers containing both
      benzothiadiazole and BODIPY units as an environment-sensitive fluorophore and as
      a reference fluorophore, respectively. The temperature-dependent fluorescence
      spectra of the thermometers enabled us to perform highly sensitive and practical
      ratiometric temperature sensing inside living mammalian cells. Intracellular
      temperatures of non-adherent MOLT-4 (human acute lymphoblastic leukaemia) and
      adherent HEK293T (human embryonic kidney) cells could be monitored with high
      temperature resolutions (0.01-1.0  degrees C) using the new cationic fluorescent
      polymeric thermometer. 

PMID- 25988200
TI  - A microfabrication-free nanoliter droplet array for nucleic acid detection
      combined with isothermal amplification.
AB  - A nanoliter droplet array based on a hydrophilic-hydrophobic patterned chip is
      developed without using microfabrication technology. Combined with the isothermal
      amplification technology, it has been applied to perform nucleic acid detection,
      showing excellent specificity and sensitivity. As a versatile platform, it is
      used to detect three gene targets successfully. 

PMID- 25988201
TI  - Synthesis of model humic substances: a mechanistic study using controllable H/D
      exchange and Fourier transform ion cyclotron resonance mass spectrometry.
AB  - The products of the oxidative coupling of phenols are frequently used as
      synthetic analogues to natural humic substances (HS) for biomedical research.
      However, their molecular compositions and exact structures remain largely
      unknown. The objective of this study was to develop a novel approach for the
      molecular-level analysis of phenolic polymerisates that is capable of
      inventorying molecular constituents and resolving their distinct structural
      formulas. For this purpose, we have synthesized the model HS using the oxidative
      coupling of a specifically designed phenylpropanoic monomer, 3-(4-hydroxy-3
      methoxyphenyl)-3-oxopropionic acid, to hydroquinone. We have characterized the
      synthesized model HS using high resolution Fourier transform ion cyclotron
      resonance mass spectrometry (FTICR MS), (1)H NMR spectroscopy, and controllable
      hydrogen/deuterium (H/D) exchange. We succeeded in the molecular inventory of the
      model HS. The assigned molecular formulas occupied the substantial space of CHO
      compositions in the Van Krevelen diagram with a maximum density found in the
      regions of tannins and lignins, resembling those of natural HS. To identify the
      exact structural formulas of the individual constituents in the model HS, we have
      applied selective H/D exchange of non-labile backbone protons by a choice of
      basic or acidic catalytic conditions followed by FTICR MS. The determined
      formulas allowed us to verify the proposed pathways of hydroxylation and
      carboxylation in the course of the phenolic coupling and to identify the
      acetylation of aromatic rings as an important side reaction. We conclude that the
      proposed analytical approach may be used to identify the molecular carriers of
      biological activity within the phenolic polymerisates and eventually within
      natural HS. 

PMID- 25988202
TI  - Facile synthesis of boron- and nitride-doped MoS2 nanosheets as fluorescent
      probes for the ultrafast, sensitive, and label-free detection of Hg(2+).
AB  - Bulk MoS2, a prototypical transition metal chalcogenide material, is an indirect
      band gap semiconductor with negligible photoluminescence. In this study, we have
      developed, for the first time, a simple and low-cost synthetic strategy to
      prepare boron- and nitrogen-doped MoS2 (B,N-MoS2) nanosheets. Through boron and
      nitrogen doping, the band gap of MoS2 increases from 1.20 eV to 1.61 eV, and the
      obtained B,N-MoS2 nanosheets exhibit an enhanced fluorescence. The B,N-MoS2
      nanosheets can be used as a green and facile sensing platform for label-free
      detection of Hg(2+) because of their high sensitivity and selectivity toward
      Hg(2+). In addition, detection can be easily accomplished through one-step rapid
      (within 2 min) operation, with a limit as low as 1 nM. This study demonstrates
      that the introduction of boron and nitrogen elements into ultrathin MoS2
      nanosheets for enhanced fluorescence properties is feasible through a facile and
      general preparation strategy and may also offer a unique idea as a potential way
      to design more efficient MoS2-based sensors and fluorescent materials. 

PMID- 25988203
TI  - A gold nanoparticle-based colorimetric probe for rapid detection of 1
      hydroxypyrene in urine.
AB  - Direct and rapid detection of 1-hydroxypyrene (1-OHP) is of great importance
      owing to its high carcinogenicity, teratogenicity and toxicity. In this study, a
      simple colorimetric assay for rapid determination of 1-OHP is reported, which is
      based on non-crosslinking aggregation of gold nanoparticles (Au NPs) induced by 1
      OHP in the presence of formic acid (FA). Initially, Au NPs were synthesized with
      citrate as the capping agent and exhibited red color. Subsequently, the addition
      of FA did not cause aggregation of Au NPs, but a proton transfer process occurred
      from FA to carboxylic anions on the surface of Au NPs with a decreased zeta
      potential. The subsequent addition of 1-OHP resulted in a further decreased zeta
      potential and an intensely hydrophobic environment, which led to a strong and
      rapid non-crosslinking aggregation of Au NPs within 5 min with the color changing
      from red to violet blue. Based on this principle, sensitive and selective
      detection of 1-OHP was achieved. The detection limit was 3.3 nM. Finally, the
      colorimetric assay was successfully applied to detect 1-OHP in a urine sample.
      This strategy provides new insights into developing colorimetric methods for on
      site and real-time detection of polycyclic aromatic hydrocarbons. 

PMID- 25988204
TI  - Note of concern.

PMID- 25988205
TI  - The American Society of Surgical Oncology travel  grant.

PMID- 25988206
TI  - EUPHA office column.

PMID- 25988207
TI  - Message from the WHO Regional Director for Europe: Investing in health over the
      life-course.

PMID- 25988208
TI  - Health and food safety: 'promotion, protection and prevention' Vytenis
      Andriukaitis, EU Commissioner for Health and Food Safety since November 2014,
      sets out his health priorities.

PMID- 25988209
TI  - Retraction. AvrXa7-Xa7 mediated defense in rice can be suppressed by
      transcriptional activator-like effectors TAL6 and TAL11a from Xanthomonas oryzae
      pv. oryzicola.

PMID- 25988211
TI  - Retraction notice to Correlation between the number and origin of  circulating
      microparticles and fibrin clot properties in patients with  coronary artery
      disease  [IJCA Journal Title 181C (2014) 147 - 148 of retracted article].

PMID- 25988210
TI  - Comments on Liu Yet al. "Effect of c-erbB2 overexpression on prognosis in
      osteosarcoma: evidence from eight studies".

PMID- 25988212
TI  - DNA methylation analysis for the diagnosis of thyroid nodules - a pilot study
      with reference to BRAF(V) (600E) mutation and cytopathology results.
AB  - OBJECTIVE: Promoter hypermethylation and the BRAF(V) (600E) mutation are both
      involved in thyroid tumorigenesis. We conducted a pilot study on the diagnosis of
      thyroid nodules by analysis of promoter hypermethylation status with reference to
      BRAF(V) (600E) mutation and cytopathology results using formalin-fixed, paraffin
      embedded (FFPE) tissues and liquid-based preparation (LBP) thyroid fine needle
      aspiration (FNA) samples to predict more reliably the possibility of papillary
      carcinoma. METHODS: We initially performed MethyLight analysis for 30 genes that
      are known to be hypermethylated in malignancies using 164 papillary carcinomas
      and 77 benign tissue samples. Five genes selected from the tissue analysis were
      subsequently analysed in 75 surgically proven benign and 66 surgically proven
      papillary carcinoma LBP FNA samples. Samples that showed two or more positive
      results among the five genes were classified as methylation positive. We also
      analysed the BRAF(V) (600E) mutation status of the FNA samples. RESULTS: We
      identified five genes that were significantly hypermethylated in malignant
      tissues: PTGS2, HOXA1, TMEFF2, p16 and PTEN. With respect to diagnostic
      potential, results obtained using the BRAF(V) (600E) mutation test combined with
      cytological examination were not significantly different from those obtained with
      cytological examination only. Combining methylation analyses with cytological
      examination or performing all three tests for diagnoses did not improve
      significantly the negative predictive values and sensitivity, but a significant
      decrease in positive predictive value and specificity was observed. CONCLUSION:
      Further studies are needed on larger samples to assess the potential value of
      methylation analysis of thyroid FNA.

PMID- 25988213
TI  - A planar chiral meta-surface for optical vortex generation and focusing.
AB  - Data capacity is rapidly reaching its limit in modern optical communications.
      Optical vortex has been explored to enhance the data capacity for its extra
      degree of freedom of angular momentum. In traditional means, optical vortices are
      generated using space light modulators or spiral phase plates, which would
      sharply decrease the integration of optical communication systems. Here we
      experimentally demonstrate a planar chiral antenna array to produce optical
      vortex from a circularly polarized light. Furthermore, the antenna array has the
      ability to focus the incident light into point, which greatly increases the power
      intensity of the generated optical vortex. This chiral antenna array may have
      potential application in highly integrated optical communication systems. 

PMID- 25988214
TI  - Polymer Brush Surfaces Showing Superhydrophobicity and Air-Bubble Repellency in a
      Variety of Organic Liquids.
AB  - Silicon (Si) substrates were modified with polyalkyl methacrylate brushes having
      different alkyl chain lengths (C(n), where n = 1, 4, 8, and 18) using ARGET-ATRP
      at ambient temperature without purging the reaction solution of oxygen. The
      dynamic hydrophobicity of these polymer brush-covered Si surfaces when submerged
      in a variety of organic solvents (1-butanol, dichloromethane, toluene, n-hexane)
      depended markedly on the alkyl chain length and to a lesser extent polymer
      solubility. Long-chain poly(stearyl methacrylate) brushes (C(n) = 18) submerged
      in toluene showed excellent water-repellant properties, having large
      advancing/receding contact angles (CAs) of 169 degrees /168 degrees  with
      negligible CA hysteresis (1 degrees ). Whereas polymer brushes with short alkyl
      chain (C(n) <= 4) had significantly worse water drop mobility because of small
      CAs (as low as 125 degrees /55 degrees ) and large CA hysteresis (up to 70
      degrees ). However, such poor dynamic dewetting behavior of these surfaces was
      found to significantly improve when water drops impacted onto the surfaces at
      moderate velocities. Under these conditions, all brush surfaces were able to
      expel water drops from their surface. In addition, our brush surfaces were also
      highly repellant toward air bubbles under all conditions, irrespective of C(n) or
      polymer solubility. These excellent surface properties were found to be vastly
      superior to the performance of conventional perfluoroalkylsilane-derived
      surfaces.

PMID- 25988215
TI  - Quorum-sensing regulators in Gram-positive bacteria: 'cherchez le peptide'.
AB  - Gram-positive bacteria can regulate gene expression at the population level via a
      mechanism known as quorum sensing. Oligopeptides serve as the signaling
      molecules; they are secreted and then are either detected at the bacterial
      surface by two-component systems or reinternalized via an oligopeptide transport
      system. In the latter case, imported peptides interact with cognate regulators
      (phosphatases or transcriptional regulators) that modulate the expression of
      target genes. These regulators help control crucial functions such as virulence,
      persistence, conjugation and competence and have been reported in bacilli,
      enterococci and streptococci. They form the rapidly growing RRNPP group. In this
      issue of Molecular Microbiology, Hoover et al. (2015) highlight the group's
      importance: they have identified a new family of regulators, Tprs (Transcription
      factor regulated by a Phr peptide), which work with internalized Phr-like
      peptides. The mechanisms underlying the expression of the genes that encode these
      internalized peptides are poorly documented. However, Hoover et al. (2015) have
      provided a new insight: an environmental molecule, glucose, can inhibit
      expression of the Phr-like peptide gene via catabolic repression. This previously
      undescribed regulatory pathway, controlling the production of a bacteriocin,
      might influence Streptococcus pneumonia's fitness in the nasopharynx, where
      galactose is present. 

PMID- 25988216
TI  - Neoadjuvant chemoradiation for rectal cancer is not associated with higher rates
      of thromboembolism.
AB  - AIM: Thromboembolism (TE) is a leading cause of death amongst cancer patients.
      The effect of neoadjuvant chemoradiotherapy (nCRT) on the risk of TE in rectal
      cancer patients is unknown. The aim of this study was to determine whether nCRT
      was associated with an increased risk of TE in patients with rectal cancer,
      either during therapy or with subsequent treatment. METHOD: This was a
      retrospective study from a prospectively maintained database at a tertiary
      referral centre. Participants included patients with rectal cancer treated
      between January 2000 and December 2013. The primary outcome was the rate of TE in
      patients with rectal cancer who had nCRT compared with those who did not.
      RESULTS: One hundred and seventy-one (7.8%) of 2181 rectal cancer patients
      developed TE. Patients who had nCRT did not have an increased incidence of TE
      compared with those who had surgery alone (81/946, 8.6% vs 94/1235, 7.6%, P =
      0.42) after a median follow-up of 95 months. Ten (1.1%) of 946 patients who
      received nCRT developed TE during or immediately after nCRT. Most TE events
      occurred in the 30-day postoperative period (70 patients, 3.2%). CONCLUSION: The
      prevalence of TE in patients with rectal cancer was 7.8%, with most events
      occurring in within 30 days of surgery. Neoadjuvant chemoradiation was not
      associated with an increased risk of TE.

PMID- 25988217
TI  - Chicken surimi fortified by omega-3 fatty acid addition: manufacturing and
      quality properties.
AB  - BACKGROUND: The meat of spent hens is hard to use owing to its small amount and
      poor quality. A washing process to remove sarcoplasmic proteins and other
      impurities can prolong the shelf life of surimi-like products. Owing to the
      benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), functional foods
      fortified with omega-3 PUFAs are increasingly being marketed. Hence, in this
      study, omega-3 FA-fortified chicken surimi was manufactured, and how to
      ameliorate its lipid peroxidation during frozen storage was investigated.
      RESULTS: A 0.10% (w/v) solution of sodium chloride (NaCl) instead of distilled
      water in the third washing step decreased (P < 0.05) myofibrillar protein loss
      and moisture content of spent hen breast protein recoveries. Oil droplets in
      fish, flaxseed or soybean oil-added chicken surimi were well distributed.
      Moreover, flaxseed oil addition increased (P < 0.05) total omega-3 FAs and omega
      3/omega-6 FA ratio, while only fish oil provided long-chain PUFAs. Oil addition
      decreased (P < 0.05) hardness and gumminess of chicken surimi, while flaxseed oil
      resulted in more (P < 0.05) yellow surimi than fish and soybean oil. Fish oil
      added samples showed higher (P < 0.05) lipid oxidation than flaxseed or soybean
      oil-added samples under -15 to -10  degrees C storage, but alpha-tocopherol
      addition ameliorated it. CONCLUSION: A novel semi-manufactured chicken surimi
      product with nutritional benefits could be developed by fortification with fish
      or flaxseed oil.

PMID- 25988218
TI  - Fluorescent Probe HKSOX-1 for Imaging and Detection of Endogenous Superoxide in
      Live Cells and In Vivo.
AB  - Superoxide anion radical (O2(*-)) is undoubtedly the most important primary
      reactive oxygen species (ROS) found in cells, whose formation and fate are
      intertwined with diverse physiological and pathological processes. Here we report
      a highly sensitive and selective O2(*-) detecting strategy involving O2(*-)
      cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We
      have synthesized three new O2(*-) fluorescent probes (HKSOX-1, HKSOX-1r for
      cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit
      excellent selectivity and sensitivity toward O2(*-) over a broad range of pH,
      strong oxidants, and abundant reductants found in cells. In confocal imaging,
      flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied
      to detect O2(*-) in multiple cellular models, such as inflammation and
      mitochondrial stress. Additionally, our probes can be efficiently applied to
      visualize O2(*-) in intact live zebrafish embryos. These probes open up exciting
      opportunities for unmasking the roles of O2(*-) in health and disease. 

PMID- 25988219
TI  - DNA entropy reveals a significant difference in complexity between housekeeping
      and tissue specific gene promoters.
AB  - BACKGROUND: The complexity of DNA can be quantified using estimates of entropy.
      Variation in DNA complexity is expected between the promoters of genes with
      different transcriptional mechanisms; namely housekeeping (HK) and tissue
      specific (TS). The former are transcribed constitutively to maintain general
      cellular functions, and the latter are transcribed in restricted tissue and cells
      types for specific molecular events. It is known that promoter features in the
      human genome are related to tissue specificity, but this has been difficult to
      quantify on a genomic scale. If entropy effectively quantifies DNA complexity,
      calculating the entropies of HK and TS gene promoters as profiles may reveal
      significant differences. RESULTS: Entropy profiles were calculated for a total
      dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587
      tissue specific (TS) human gene promoters. The mean profiles show the TS
      promoters have a significantly lower entropy (p<2.2e-16) than HK gene promoters.
      The entropy distributions for the 3 datasets show that promoter entropies could
      be used to identify novel HK genes. CONCLUSION: Functional features comprise DNA
      sequence patterns that are non-random and hence they have lower entropies. The
      lower entropy of TS gene promoters can be explained by a higher density of
      positive and negative regulatory elements, required for genes with complex
      spatial and temporary expression.

PMID- 25988220
TI  - Identification of evolutionarily conserved Momordica charantia microRNAs using
      computational approach and its utility in phylogeny analysis.
AB  - Momordica charantia (bitter gourd, bitter melon) is a monoecious Cucurbitaceae
      with anti-oxidant, anti-microbial, anti-viral and anti-diabetic potential.
      Molecular studies on this economically valuable plant are very essential to
      understand its phylogeny and evolution. MicroRNAs (miRNAs) are conserved, small,
      non-coding RNA with ability to regulate gene expression by bind the 3' UTR region
      of target mRNA and are evolved at different rates in different plant species. In
      this study we have utilized homology based computational approach and identified
      27 mature miRNAs for the first time from this bio-medically important plant. The
      phylogenetic tree developed from binary data derived from the data on
      presence/absence of the identified miRNAs were noticed to be uncertain and
      biased. Most of the identified miRNAs were highly conserved among the plant
      species and sequence based phylogeny analysis of miRNAs resolved the above
      difficulties in phylogeny approach using miRNA. Predicted gene targets of the
      identified miRNAs revealed their importance in regulation of plant developmental
      process. Reported miRNAs held sequence conservation in mature miRNAs and the
      detailed phylogeny analysis of pre-miRNA sequences revealed genus specific
      segregation of clusters. 

PMID- 25988221
TI  - Hospitalization frequency and charges for neurocysticercosis, United States, 2003
      2012.
AB  - Neurocysticercosis, brain infection with Taenia solium larval cysts, causes
      substantial neurologic illness around the world. To assess the effect of
      neurocysticercosis in the United States, we reviewed hospitalization discharge
      data in the Nationwide Inpatient Sample for 2003-2012 and found an estimated
      18,584 hospitalizations for neurocysticercosis and associated hospital charges
      totaling >US $908 million. The risk for hospitalization was highest among
      Hispanics (2.5/100,000 population), a rate 35 times higher than that for the non
      Hispanic white population. Nearly three-quarters of all hospitalized patients
      with neurocysticercosis were Hispanic. Male sex and age 20-44 years also incurred
      increased risk. In addition, hospitalizations and associated charges related to
      cysticercosis far exceeded those for malaria and were greater than for those for
      all other neglected tropical diseases combined. Neurocysticercosis is an
      increasing public health concern in the United States, especially among
      Hispanics, and costs the US health care system a substantial amount of money. 

PMID- 25988222
TI  - Orbital nematic order and interplay with magnetism in the two-orbital Hubbard
      model.
AB  - Motivated by the recent angle-resolved photoemission spectroscopy (ARPES) on FeSe
      and iron pnictide families of iron-based superconductors, we have studied the
      orbital nematic order and its interplay with antiferromagnetism within the two
      orbital Hubbard model. We used random phase approximation (RPA) to calculate the
      dependence of the orbital and magnetic susceptibilities on the strength of
      interactions and electron density (doping). To account for strong electron
      correlations not captured by RPA, we further employed non-perturbative
      variational cluster approximation (VCA) capable of capturing symmetry broken
      magnetic and orbitally ordered phases. Both approaches show that the electron and
      hole doping affect the two orders differently. While hole doping tends to
      suppress both magnetism and orbital ordering, the electron doping suppresses
      magnetism faster. Crucially, we find a realistic parameter regime for moderate
      electron doping that stabilizes orbital nematicity in the absence of long-range
      antiferromagnetic order. This is reminiscent of the non-magnetic orbital nematic
      phase observed recently in FeSe and a number of iron pnictide materials and
      raises the possibility that at least in some cases, the observed electronic
      nematicity may be primarily due to orbital rather than magnetic fluctuations. 

PMID- 25988223
TI  - Global features of functional brain networks change with contextual disorder.
AB  - It is known that features of stimuli in the environment affect the strength of
      functional connectivity in the human brain. However, investigations to date have
      not converged in determining whether these also impact functional networks'
      global features, such as modularity strength, number of modules, partition
      structure, or degree distributions. We hypothesized that one environmental
      attribute that may strongly impact global features is the temporal regularity of
      the environment, as prior work indicates that differences in regularity impact
      regions involved in sensory, attentional and memory processes. We examined this
      with an fMRI study, in which participants passively listened to tonal series that
      had identical physical features and differed only in their regularity, as defined
      by the strength of transition structure between tones. We found that series
      regularity induced systematic changes to global features of functional networks,
      including modularity strength, number of modules, partition structure, and degree
      distributions. In tandem, we used a novel node-level analysis to determine the
      extent to which brain regions maintained their within-module connectivity across
      experimental conditions. This analysis showed that primary sensory regions and
      those associated with default-mode processes are most likely to maintain their
      within-module connectivity across conditions, whereas prefrontal regions are
      least likely to do so. Our work documents a significant capacity for global-level
      brain network reorganization as a function of context. These findings suggest
      that modularity and other core, global features, while likely constrained by
      white-matter structural brain connections, are not completely determined by them.

PMID- 25988224
TI  - Subjective illusion of control modulates striatal reward anticipation in
      adolescence.
AB  - The perception of control over the environment constitutes a fundamental
      biological adaptive mechanism, especially during development. Previous studies
      comparing an active choice condition with a passive no-choice condition showed
      that the neural basis of this mechanism is associated with increased activity
      within the striatum and the prefrontal cortex. In the current study, we aimed to
      investigate whether subjective belief of control in an uncertain gambling
      situation induces elevated activation in a cortico-striatal network. We
      investigated 79 adolescents (age range: 13-16years) during reward anticipation
      with a slot machine task using functional magnetic resonance imaging. We assessed
      post-experimentally whether the participants experienced a subjective illusion of
      control on winning or losing in this task that was objectively not given.
      Nineteen adolescents experienced an illusion of control during slot machine
      gambling. This illusion of control group showed an increased neural activity
      during reward anticipation within a cortico-striatal network including ventral
      striatum (VS) as well as right inferior frontal gyrus (rIFG) relative to the
      group reporting no illusion of control. The rIFG activity was inversely
      associated with impulsivity in the no illusion of control group. The subjective
      belief about control led to an elevated ventral striatal activity, which is known
      to be involved in the processing of reward. This finding strengthens the notion
      that subjectively perceived control, not necessarily the objective presence of
      control, affects striatal reward-related processing. 

PMID- 25988225
TI  - The aging brain shows less flexible reallocation of cognitive resources during
      dual-task walking: A mobile brain/body imaging (MoBI) study.
AB  - Aging is associated with reduced abilities to selectively allocate attention
      across multiple domains. This may be particularly problematic during everyday
      multitasking situations when cognitively demanding tasks are performed while
      walking. Due to previous limitations in neuroimaging technology, much remains
      unknown about the cortical mechanisms underlying resource allocation during
      locomotion. Here, we utilized an EEG-based mobile brain/body imaging (MoBI)
      technique that integrates high-density event-related potential (ERP) recordings
      with simultaneously acquired foot-force sensor data to monitor gait patterns and
      brain activity concurrently. To assess effects of motor load on cognition we
      evaluated young (N=17; mean age=27.2) and older adults (N=16; mean age=63.9) and
      compared behavioral and ERP measures associated with performing a Go/No-Go
      response inhibition task as participants sat stationary or walked on a treadmill.
      Stride time and variability were also measured during task performance and
      compared to stride parameters obtained without task performance, thereby
      assessing effects of cognitive load on gait. Results showed that older, but not
      young adults' accuracy dropped significantly when performing the inhibitory task
      while walking. Young adults revealed ERP modulations at relatively early (N2
      amplitude reduction) and later (earlier P3 latency) stages within the processing
      stream as motor load increased while walking. In contrast, older adults' ERP
      modulations were limited to later processing stages (increased P3 amplitude) of
      the inhibitory network. The relative delay and attenuation of ERP modulations
      accompanied by behavioral costs in older participants might indicate an age
      associated loss in flexible resource allocation across multiple tasks. Better
      understanding of the neural underpinnings of these age-related changes may lead
      to improved strategies to reduce fall risk and enhance mobility in aging. 

PMID- 25988227
TI  - Not all declarative memories are created equal: Fast Mapping as a direct route to
      cortical declarative representations.
AB  - Memory formation for newly acquired associations typically depends on hippocampal
      neocortical interactions. Through the process of system-consolidation, the
      mnemonic binding role of the hippocampus is subsequently replaced by cortical
      hubs, such as the ventromedial prefrontal cortex (vmPFC) or the anterior temporal
      lobe (ATL). Here, using BOLD-fMRI, we compared retrieval of semantic associations
      acquired through Fast Mapping (FM), an incidental, exclusion-based learning
      procedure, to retrieval of similar associations that were intentionally acquired
      through Explicit Encoding (EE). Despite an identical retrieval task, the encoding
      histories of the retrieved semantic associations (FM vs. EE) induced distinct
      neural substrates and disparate related neural dynamics in time. Retrieval of
      associations acquired through EE engaged the expected hippocampal and vmPFC
      related networks. Furthermore, retrieval intentionally encoded associations gave
      rise to a typical overnight increase in engagement of the vmPFC and increased
      vmPFC-hippocampal-neocortical functional connectivity. On the other hand,
      retrieval of associations acquired through FM immediately engaged an ATL related
      network that typically supports well-established semantic knowledge, a network
      that did not engage the hippocampus and the vmPFC. Moreover, FM learning was
      associated with minimal overnight changes in the BOLD responses and in the
      functional connectivity. Our findings indicate that FM may induce a direct, ATL
      mediated acquisition and retention of novel arbitrary associations, bypassing the
      initial hippocampal-cortical representation phase. A direct, ATL-mediated
      vocabulary acquisition through FM could support the learning and retention of new
      associations in young children with presumably an immature hippocampal system,
      and possibly even in amnesic adults with hippocampal lesions. 

PMID- 25988226
TI  - Whole brain mapping of visual and tactile convergence in the macaque monkey.
AB  - The proposal that sensory processing is achieved in segregated anatomical
      pathways has been profoundly revisited following the description of cross-modal
      anatomical connections both at higher and at lower processing levels. However, an
      understanding of the cortical extent of these long range cross-modal functional
      influences has been missing. Here, we use functional magnetic resonance imaging
      (fMRI) to map, in the non-human primate brain, the cortical regions which are
      activated by both visual and tactile stimulations. We describe an unprecedented
      pattern of functional visuo-tactile convergence, encompassing both low-level
      visual and somatosensory areas and multiple higher-order associative areas. We
      also show that the profile of this convergence depends on the physical properties
      of the mapping stimuli, indicating that visuo-tactile convergence is most
      probably even more prevailing than what we actually describe. Overall, these
      observations substantiate the view that the brain is massively multisensory. 

PMID- 25988228
TI  - Simultaneous EEG-fMRI reveals brain networks underlying recognition memory ERP
      old/new effects.
AB  - The mapping of event-related potentials (ERP) on functional magnetic resonance
      imaging (fMRI) data remains difficult as scalp electroencephalography (EEG) is
      assumed to be largely insensitive to deep brain structures. Simultaneous
      recordings of EEG and fMRI might be helpful in reconciling surface ERPs with
      hemodynamic activations in medial temporal lobe structures related to recognition
      memory. EEG and imaging studies provide evidence for two independent processes
      underlying recognition memory, namely recollection and familiarity. Recollection
      reflects the conscious retrieval of contextual information about a specific
      episode, while familiarity refers to an acontextual feeling of knowing. Both
      processes were related to two spatiotemporally different ERP effects, namely the
      early mid-frontal old/new effect (familiarity) and the late parietal old new
      effect (recollection). We conducted an exploratory simultaneous EEG-fMRI study
      using a recognition memory paradigm to investigate which brain activations are
      modulated in relation to the ERP old/new effects. To this end we examined 17
      participants in a yes/no recognition task with word stimuli. Single-trial
      amplitudes of ERP old/new effects were related to the hemodynamic signal in an
      EEG-informed fMRI analysis for a subset of 12 subjects. FMRI activation in the
      right dorsolateral prefrontal cortex and the right intraparietal sulcus was
      associated with the amplitude of the early frontal old/new effect (350-550ms),
      and activation in the right posterior hippocampus, parahippocampal cortex and
      retrosplenial cortex was associated with the amplitude of the late parietal old
      new effect (580-750ms). These results provide the first direct link between
      electrophysiological and hemodynamic correlates of familiarity and recollection.
      Moreover, these findings in healthy subjects complement data from intracranial
      ERP recordings in epilepsy patients and lesion studies in hypoxia patients. 

PMID- 25988230
TI  - Elevated expression levels of lysyl oxidases protect against aortic aneurysm
      progression in Marfan syndrome.
AB  - Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic
      dissections. The condition is caused by mutations in the gene encoding fibrillin
      1, an essential component in the formation of elastic fibers. While experimental
      findings in animal models of the disease have shown the involvement of
      transforming growth factor-beta (TGF-beta)- and angiotensin II-dependent
      pathways, alterations in the vascular extracellular matrix (ECM) may also play a
      role in the onset and progression of the aortic disease. Lysyl oxidases (LOX) are
      extracellular enzymes, which initiates the formation of covalent cross-linking of
      collagens and elastin, thereby contributing to the maturation of the ECM. Here we
      have explored the role of LOX in the formation of aortic aneurysms in MFS. We
      show that aortic tissue from MFS patients and MFS mouse model (Fbn1(C1039G/+))
      displayed enhanced expression of the members of the LOX family, LOX and LOX-like
      1 (LOXL1), and this is associated with the formation of mature collagen fibers.
      Administration of a LOX inhibitor for 8weeks blocked collagen accumulation and
      aggravated elastic fiber impairment, and these effects correlated with the
      induction of a strong and rapidly progressing aortic dilatation, and with
      premature death in the more severe MFS mouse model, Fbn1(mgR/mgR), without any
      significant effect on wild type animals. This detrimental effect occurred
      preferentially in the ascending portion of the aorta, with little or no
      involvement of the aortic root, and was associated to an overactivation of both
      canonical and non-canonical TGF-beta signaling pathways. The blockade of
      angiotensin II type I receptor with losartan restored TGF-beta signaling
      activation, normalized elastic fiber impairment and prevented the aortic
      dilatation induced by LOX inhibition in Fbn1(C1039G/+) mice. Our data indicate
      that LOX enzymes and LOX-mediated collagen accumulation play a critical
      protective role in aneurysm formation in MFS. 

PMID- 25988229
TI  - Vanderbilt University Institute of Imaging Science Center for Computational
      Imaging XNAT: A multimodal data archive and processing environment.
AB  - The Vanderbilt University Institute for Imaging Science (VUIIS) Center for
      Computational Imaging (CCI) has developed a database built on XNAT housing over a
      quarter of a million scans. The database provides framework for (1) rapid
      prototyping, (2) large scale batch processing of images and (3) scalable project
      management. The system uses the web-based interfaces of XNAT and REDCap to allow
      for graphical interaction. A python middleware layer, the Distributed Automation
      for XNAT (DAX) package, distributes computation across the Vanderbilt Advanced
      Computing Center for Research and Education high performance computing center.
      All software are made available in open source for use in combining portable
      batch scripting (PBS) grids and XNAT servers. 

PMID- 25988232
TI  - Phthalate esters in main source water and drinking water of Zhejiang Province
      (China): Distribution and health risks.
AB  - To evaluate the distributions and health risks of phthalate esters in the main
      source water and corresponding drinking water of Zhejiang Province, the
      concentrations of 16 phthalate esters in water samples from 19 sites were
      measured from samples taken in the dry season and wet season. The concentration
      of the total phthalate ester congeners in source water ranged from 1.07 MUg/L to
      7.12 MUg/L in the wet season, from 0.01 MUg/L to 1.58 MUg/L in the dry season,
      from 1.18 MUg/L to 15.28 MUg/L from drinking water in the wet season, and from
      0.16 MUg/L to 1.86 MUg/L from drinking water in the dry season. Of the 16
      phthalate esters, dimethyl phthalate, dibutyl phthalate, di-(2-ethyl-hexyl)
      phthalate, di-iso-butyl phthalate, bis-2-n-butoxyethyl phthalate, and
      dicyclohexyl phthalate were present in the samples analyzed, dominated by di-iso
      butyl phthalate and di-(2-ethyl-hexyl) phthalate. The concentrations of phthalate
      esters in the wet season were all relatively higher than those in the dry season,
      and the drinking water had higher concentrations of phthalate esters than source
      water. The phthalate ester congeners studied pose little health risk to nearby
      citizens. Environ Toxicol Chem 2015;34:2205-2212. (c) 2015 SETAC. 

PMID- 25988231
TI  - Losartan treatment attenuates tumor-induced myocardial dysfunction.
AB  - Fatigue and muscle wasting are common symptoms experienced by cancer patients.
      Data from animal models demonstrate that angiotensin is involved in tumor-induced
      muscle wasting, and that tumor growth can independently affect myocardial
      function, which could contribute to fatigue in cancer patients. In clinical
      studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the
      development of chemotherapy-induced cardiovascular dysfunction, suggesting a
      mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the
      present study, we investigated whether an angiotensin (AT) 1-receptor antagonist
      could prevent the development of tumor-associated myocardial dysfunction. METHODS
      AND RESULTS: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1
      mice at 8weeks of age. Simultaneously, mice were administered Losartan (10mg/kg)
      daily via their drinking water. In vivo echocardiography, blood pressure, in
      vitro cardiomyocyte function, cell proliferation assays, and measures of systemic
      inflammation and myocardial protein degradation were performed 19days following
      tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle
      mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated
      myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated
      tumor-associated alterations in calcium signaling in cardiomyocytes, which was
      associated with improved myocyte contraction velocity, systolic function, and
      blood pressures in the hearts of tumor-bearing mice. CONCLUSIONS: These data
      suggest that Losartan may mitigate tumor-induced myocardial dysfunction and
      inflammation.

PMID- 25988233
TI  - Phenotypic integration in the feeding system of the eastern diamondback
      rattlesnake (Crotalus adamanteus).
AB  - Selection can vary geographically across environments and temporally over the
      lifetime of an individual. Unlike geographic contexts, where different selective
      regimes can act on different alleles, age-specific selection is constrained to
      act on the same genome by altering age-specific expression. Snake venoms are
      exceptional traits for studying ontogeny because toxin expression variation
      directly changes the phenotype; relative amounts of venom components determine,
      in part, venom efficacy. Phenotypic integration is the dependent relationship
      between different traits that collectively produce a complex phenotype and, in
      venomous snakes, may include traits as diverse as venom, head shape and fang
      length. We examined the feeding system of the eastern diamondback rattlesnake
      (Crotalus adamanteus) across environments and over the lifetime of individuals
      and used a genotype-phenotype map approach, protein expression data and
      morphological data to demonstrate that: (i) ontogenetic effects explained more of
      the variation in toxin expression variation than geographic effects, (ii) both
      juveniles and adults varied geographically, (iii) toxin expression variation was
      a result of directional selection and (iv) different venom phenotypes covaried
      with morphological traits also associated with feeding in temporal (ontogenetic)
      and geographic (functional) contexts. These data are the first to demonstrate, to
      our knowledge, phenotypic integration between multiple morphological characters
      and a biochemical phenotype across populations and age classes. We identified
      copy number variation as the mechanism driving the difference in the venom
      phenotype associated with these morphological differences, and the parallel
      mitochondrial, venom and morphological divergence between northern and southern
      clades suggests that each clade may warrant classification as a separate
      evolutionarily significant unit. 

PMID- 25988234
TI  - Structure-activity relationship of Cr/Ti-PILC catalysts using a pre-modification
      method for NO oxidation and their surface species study.
AB  - The performances of Cr/Ti-PILC catalysts, which were prepared by the pre
      modification method, are studied for the selective catalytic oxidation of NO. The
      aim of this paper is to elucidate the detailed relationship between physical
      nanoparticle structure and chemical properties. The maximum NO conversion over
      the Cr-HP(3)/TP catalyst reached 71.4% at 280  degrees C. The catalysts were
      characterized by powder X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray photoelectron
      spectroscopy (XPS), temperature-programmed reduction of H2 (H2-TPR), temperature
      programmed desorption (TPD) and diffuse reflectance infrared Fourier transform
      spectroscopy (DRIFTS) techniques. The characterization results demonstrated that
      the enhanced catalytic activity was ascribed to several beneficial effects, which
      were caused by the pre-modification such as the inhibition of crystallite size,
      improvement of Cr species dispersion and increase of the amount of active sites.
      XPS and FTIR experiments indicated that two Cr(VI) species, oxidized state CrO3
      and chromate species with the anionic form, were generated via pre-modification,
      which played different roles in the catalytic reaction. In addition, the TPR and
      TPD results suggest that the increased active sites (Cr(VI) species) were
      conducive for the preferential adsorption and activation of NO. Furthermore,
      DRIFTS results revealed that the intermediates, NO(+) and nitrates, interacted
      quickly to generate gaseous NO2.

PMID- 25988236
TI  - KPC and NDM-1 genes in related Enterobacteriaceae strains and plasmids from
      Pakistan and the United States.
AB  - To characterize the genomic context of New Delhi metallo-beta-lactamase-1 (NDM-1)
      and Klebsiella pneumoniae carbapenemase (KPC), we sequenced 78 Enterobacteriaceae
      isolates from Pakistan and the United States encoding KPC, NDM-1, or no
      carbapenemase. High similarities of the results indicate rapid spread of
      carbapenem resistance between strains, including globally disseminated pathogens.

PMID- 25988237
TI  - Exploration of the cognitive, adaptive and behavioral functioning of patients
      affected with Bardet-Biedl syndrome.
AB  - The aim of the study was to investigate the behavioral phenotype of patients
      affected with Bardet-Biedl syndrome (BBS). Twenty-four patients with molecularly
      confirmed diagnosis of BBS (6-38 years old) were evaluated using standardized
      neuropsychological tests. Results were compared with normative data. The mean
      intellectual functioning of participants fell 1.5 standard deviations below
      normal expectations; though, the majority of participants (75-80%) did not
      display an intellectual disability. The group's mean performance on most
      cognitive tasks and all scales of adaptive functioning was significantly weaker
      than norms. The majority (55-60%) of participants displayed broadly average
      verbal fluency and auditory rote learning, while 22-40% were severely impaired in
      the same areas. The majority of participants were severely impaired in perceptual
      reasoning (53%), attentional capacity (69%), and functional independence (74%).
      Symptoms associated with Autism were reported for 77% of participants. Behavioral
      issues were unrelated to intellectual ability but significantly correlated with
      adaptive functioning. This first neurocognitive evaluation of a molecularly
      confirmed cohort of BBS patients shows that the majority of patients experience
      significant difficulties with perceptual intellectual abilities, auditory
      attentional capacity, adaptive independence, and behavior. The frequency of
      autism-related symptoms far exceeds the incidence rate of diagnosed autism in
      general and warrants further investigations.

PMID- 25988238
TI  - Motion and gravity effects in the precision of quantum clocks.
AB  - We show that motion and gravity affect the precision of quantum clocks. We
      consider a localised quantum field as a fundamental model of a quantum clock
      moving in spacetime and show that its state is modified due to changes in
      acceleration. By computing the quantum Fisher information we determine how
      relativistic motion modifies the ultimate bound in the precision of the
      measurement of time. While in the absence of motion the squeezed vacuum is the
      ideal state for time estimation, we find that it is highly sensitive to the
      motion-induced degradation of the quantum Fisher information. We show that
      coherent states are generally more resilient to this degradation and that in the
      case of very low initial number of photons, the optimal precision can be even
      increased by motion. These results can be tested with current technology by using
      superconducting resonators with tunable boundary conditions. 

PMID- 25988239
TI  - Pelvic drainage during removal of dialysis catheter decreases the risk of
      subsequent intra-abdominal complications in refractory peritoneal dialysis
      related peritonitis.
AB  - AIM: Some patients with refractory peritoneal dialysis-related peritonitis
      continue to develop intra-abdominal complications despite removal of the
      peritoneal catheter. Repeated percutaneous drainage or open laparotomy is often
      required, and mortality is not uncommon. The benefits of pelvic drainage
      placement during catheter removal in decreasing these complications and
      interventions remain unproven. METHODS: Forty-six patients with refractory
      peritonitis who underwent removal of a Tenckhoff catheter between 1991 and 2013
      were reviewed retrospectively. Twelve patients had pelvic drainage using closed
      active suction devices during catheter removal (drainage group). The remaining 34
      patients underwent catheter removal without drainage (non-drainage group). The
      outcomes measured were the development of intra-abdominal complications and the
      requirement for repeated percutaneous drainage or open laparotomy within 90 days
      after the catheter removal. RESULTS: Baseline characteristics were similar with
      the exception of a higher median number of previous peritonitis episodes in the
      drainage group compared with the non-drainage group (2 vs 0, P = 0.02). During
      the follow-up period, intra-abdominal complications occurred in 15 (44%) of 34
      patients in the non-drainage group, compared with one (8%) of 12 patients in the
      drainage group (P = 0.03). Twelve (35%) patients in the non-drainage group
      required repeated percutaneous drainage or open laparotomy for management,
      compared with zero (0%) patients in the drainage group (P = 0.02). Drain tubes
      were removed at a median of 6 days (inter-quartile range: 5-10) without
      complications. CONCLUSIONS: In the management of refractory peritonitis, pelvic
      drainage during removal of dialysis catheter decreases the risk of subsequent
      intra-abdominal complications and invasive interventions.

PMID- 25988240
TI  - Effect-directed identification of endocrine disruptors in plastic baby teethers.
AB  - Concerns have been raised regarding the human health effects of endocrine
      disrupting chemicals (EDCs), many of which are associated with and leaching from
      plastics. As infants are particularly vulnerable to EDCs, we have investigated
      whether plastic teethers for babies represent a relevant source of exposure.
      Applying effect-directed analysis, we use bioassays to screen teethers, toys used
      to soothe a baby's teething ache, for endocrine activity and chemical analysis to
      identify the causative compounds. We detected significant endocrine activity in
      two of 10 plastic teethers. Those samples leached estrogenic and/or
      antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast
      Antiandrogen Screen. After sample fractionation, gas chromatography-mass
      spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben
      were responsible for the observed estrogenic and antiandrogenic activity in one
      product. The second product is likely to contain at least six different
      antiandrogenic compounds that remain so far unidentified. This study demonstrates
      that plastic teethers can be a source of infant exposure to well-established and
      unknown EDCs. Because of their limited value to the product, but potential
      toxicity, manufacturers should critically revisit the use of parabens in plastic
      teethers and further toys. Moreover, plastic teethers might leach EDCs that
      escape routine analysis and, thus, toxicological evaluation. The resulting
      uncertainty in product safety poses a problem to consumers, producers and
      regulators that remain to be resolved.

PMID- 25988243
TI  - Development of ssDNA aptamers as potent inhibitors of Mycobacterium tuberculosis
      acetohydroxyacid synthase.
AB  - Acetohydroxyacid synthase (AHAS) from Mycobacterium tuberculosis (Mtb) is a
      promising potential drug target for an emerging class of new anti-tuberculosis
      agents. In this study, we identify short (30-mer) single-stranded DNA aptamers as
      a novel class of potent inhibitors of Mtb-AHAS through an in vitro DNA-SELEX
      method. Among all tested aptamers, two candidate aptamers (Mtb-Apt1 and Mtb-Apt6)
      demonstrated the greatest inhibitory potential against Mtb-AHAS activity with
      IC50 values in the low nanomolar range (28.94+/-0.002 and 22.35+/-0.001 nM
      respectively). Interestingly, inhibition kinetics analysis of these aptamers
      showed different modes of enzyme inhibition (competitive and mixed type of
      inhibition respectively). Secondary structure-guided mutational modification
      analysis of Mtb-Apt1 and Mtb-Apt6 identified the minimal region responsible for
      their inhibitory action and consequently led to 17-mer and 20-mer shortened
      aptamers that retained equivalent or greater inhibitory potential. Notably, a
      modeling and docking exercise investigated the binding site of these two potent
      inhibitory aptamers on the target protein and showed possible involvement of some
      key catalytic dimer interface residues of AHAS in the DNA-protein interactions
      that lead to its potent inhibition. Importantly, these two short candidate
      aptamers, Mtb-Apt1 (17-mer) and Mtb-Apt6 (20-mer), also demonstrated significant
      growth inhibition against multidrug-resistant (MDR-TB) and extensively drug
      resistant (XDR-TB) strains of tuberculosis with very low MIC of 5.36 MUg/ml and
      6.24 MUg/ml, respectively and no significant cytotoxicity against mammalian cell
      line. This is the first report of functional inhibitory aptamers against Mtb-AHAS
      and provides the basis for development of these aptamers as novel and strong anti
      tuberculosis agents.

PMID- 25988242
TI  - Differential Regulation of Vascular Endothelial Growth Factors by Promoter
      targeted shRNAs.
AB  - Vascular endothelial growth factors (VEGFs) and their receptors (VEGF-R) are
      central regulators of vasculogenesis, angiogenesis, and lymphangiogenesis. They
      contribute to many vascular-related pathologies, and hence VEGF-targeted
      therapies have been widely sought after. In this study, the authors investigated
      the ability of promoter-targeted small hairpin RNAs (shRNAs) to regulate VEGF-A,
      VEGF-C and VEGF-R1 in different cell lines. The authors identified shRNAs that
      can upregulate hVEGF-C at both the mRNA and protein levels, and differentially
      regulate hVEGF-A depending on the cell type. Likewise, the authors identified
      shRNA that downregulated VEGF-R1 gene expression. Hence, promoter-targeted shRNAs
      can affect endogenous gene expression not only bimodally, but also differentially
      in a cell-type specific manner. Importantly, all three genes tested were
      regulated by at least one shRNA, supporting the idea that nuclear RNA
      interference is a widespread phenomenon. The level of regulation across the panel
      of shRNAs varied maximally from a 2.2-fold increase to a 4-fold decrease. This
      level of change should be useful in fine-tuning and modulating target gene
      expression, which for potent molecules, such as VEGF-A and VEGF-C, can be very
      beneficial. These promoter-targeted shRNAs may facilitate the design and
      development of targeted, context-dependent strategies for both pro- and
      antiangiogenic therapies for the treatment of vascular-related pathologies. 

PMID- 25988244
TI  - The intrinsically disordered protein LEA7 from Arabidopsis thaliana protects the
      isolated enzyme lactate dehydrogenase and enzymes in a soluble leaf proteome
      during freezing and drying.
AB  - The accumulation of Late Embryogenesis Abundant (LEA) proteins in plants is
      associated with tolerance against stresses such as freezing and desiccation. Two
      main functions have been attributed to LEA proteins: membrane stabilization and
      enzyme protection. We have hypothesized previously that LEA7 from Arabidopsis
      thaliana may stabilize membranes because it interacts with liposomes in the dry
      state. Here we show that LEA7, contrary to this expectation, did not stabilize
      liposomes during drying and rehydration. Instead, it partially preserved the
      activity of the enzyme lactate dehydrogenase (LDH) during drying and freezing.
      Fourier-transform infrared (FTIR) spectroscopy showed no evidence of aggregation
      of LDH in the dry or rehydrated state under conditions that lead to complete loss
      of activity. To approximate the complex influence of intracellular conditions on
      the protective effects of a LEA protein in a convenient in-vitro assay, we
      measured the activity of two Arabidopsis enzymes (glucose-6-P dehydrogenase and
      ADP-glucose pyrophosphorylase) in total soluble leaf protein extract (Arabidopsis
      soluble proteome, ASP) after drying and rehydration or freezing and thawing. LEA7
      partially preserved the activity of both enzymes under these conditions,
      suggesting its role as an enzyme protectant in vivo. Further FTIR analyses
      indicated the partial reversibility of protein aggregation in the dry ASP during
      rehydration. Similarly, aggregation in the dry ASP was strongly reduced by LEA7.
      In addition, mixtures of LEA7 with sucrose or verbascose reduced aggregation more
      than the single additives, presumably through the effects of the protein on the H
      bonding network of the sugar glasses. 

PMID- 25988241
TI  - Rheumatoid Arthritis, Anti-Cyclic Citrullinated Peptide Positivity, and
      Cardiovascular Disease Risk in the Women's Health Initiative.
AB  - OBJECTIVE: To evaluate the incidence of cardiovascular disease (CVD) morbidity
      and mortality over the course of 10 years among the more than 160,000
      postmenopausal women in the Women's Health Initiative (WHI) in relation to self
      reported rheumatoid arthritis (RA), taking disease-modifying antirheumatic drugs
      (DMARDs), anti-cyclic citrullinated peptide (anti-CCP) positivity, rheumatoid
      factor (RF) positivity, CVD risk factors, joint pain, and inflammation (white
      blood cell count and interleukin-6 levels). METHODS: Anti-CCP and RF were
      measured in a sample of WHI participants with self-reported RA (n = 9,988). RA
      was classified as self-reported RA plus anti-CCP positivity and/or taking DMARDs.
      Anti-CCP-negative women with self-reported RA and not taking DMARDs were
      classified as having "unverified RA." RESULTS: Age-adjusted rates of coronary
      heart disease (CHD), stroke, CVD, fatal CVD, and total mortality were higher in
      women with RA than in women with no reported RA, with multivariable-adjusted
      hazard ratios of 1.46 (95% confidence interval [95% CI] 1.17-1.83) for CHD and
      2.55 (95% CI 1.86-3.51) for fatal CVD. Among women with RA, anti-CCP positivity
      and RF positivity were not significantly associated with higher risk of any
      outcomes, despite slightly higher risk of death for those who were anti-CCP
      positive than for those who were anti-CCP negative. Joint pain severity and CVD
      risk factors were strongly associated with CVD risk, even in women with no
      reported RA. CVD incidence was increased in women with RA versus women with no
      reported RA at almost all risk factor levels, except for low levels of joint pain
      or inflammation. Among women with RA, inflammation was more strongly associated
      with fatal CVD and total mortality than with CHD or CVD. CONCLUSION: Among
      postmenopausal women, RA was associated with 1.5-2.5-fold higher CVD risk. CVD
      risk was strongly associated with CVD risk factors, joint pain severity, and
      inflammation, but not with anti-CCP positivity or RF positivity.

PMID- 25988247
TI  - CO2 laser emission modes to control enamel erosion.
AB  - Considering the importance and prevalence of dental erosion, the aim of this in
      vitro study was to evaluate the influence of different modes of pulse emission of
      CO2 laser associated or not to acidulated phosphate fluoride (APF) 1.23% gel, in
      controlling enamel erosion by profilometry. Ninety-six fragments of bovine enamel
      were flattened and polished, and the specimens were subjected to initial erosive
      challenge with hydrochloric acid (pH = 2). Specimens were randomly assigned
      according to surface treatment: APF 1.23% gel and gel without fluoride (control),
      and subdivided according to the modes of pulse CO2 laser irradiation: no
      irradiation (control), continuous, ultrapulse, and repeated pulse (n = 12). After
      surface treatment, further erosive challenges were performed for 5 days, 4 * 2
      min/day. Enamel structure loss was quantitatively determined by a profilometer,
      after surface treatment and after 5 days of erosive challenges. Two-away ANOVA
      revealed a significant difference between the pulse emission mode of the CO2
      laser and the presence of fluoride (P <= 0.05). The Duncan's test showed that CO2
      laser irradiation in continuous mode and the specimens only received fluoride,
      promoted lower enamel loss than that other treatments. A lower dissolution of the
      enamel prisms was observed when it was irradiated with CO2 laser in continuous
      mode compared other groups. It can be concluded that CO2 laser irradiation in
      continuous mode was the most effective to control the enamel structure loss
      submitted to erosive challenges with hydrochloric acid.

PMID- 25988248
TI  - Prevalence of cholera risk factors between migrant Haitians and Dominicans in the
      Dominican Republic.
AB  - OBJECTIVE: To determine whether cholera risk factor prevalence in the Dominican
      Republic can be explained by nationality, independent of other factors, given the
      vulnerability of many Haitians in the country and the need for targeted
      prevention. METHODS: A cross-sectional, observational household survey (103
      Haitian and 260 Dominican) was completed in 18 communities in July 2012. The
      survey included modules for demographics, knowledge, socioeconomic status, and
      access to adequate water, sanitation, and hygiene (WASH) infrastructure. Logistic
      regression assessed differential access to WASH infrastructure and Poisson
      regression assessed differences in cholera knowledge, controlling for potential
      confounders. RESULTS: Dominican and Haitian households differed on demographic
      characteristics. Haitians had lower educational attainment, socioeconomic status,
      and less knowledge of cholera than Dominicans (adjusted odds ratio [aOR] = 0.66;
      95% confidence interval [95%CI] = 0.55-0.81). Access to improved drinking water
      was low for both groups, but particularly low among rural Haitians (aOR = 0.21;
      95%CI: 0.04-1.01). No differences were found in access to sanitation after
      adjusting for sociodemographic confounders (aOR = 1.00; 95%CI: 0.57-1.76).
      CONCLUSIONS: Urban/rural geography and socioeconomic status play a larger role in
      cholera risk factor prevalence than nationality, indicating that Haitians'
      perceived vulnerability to cholera is confounded by contextual factors.
      Understanding the social dynamics that lead to cholera risk can inform control
      strategies, leading to better targeting and the possibility of eliminating
      cholera from the island.

PMID- 25988249
TI  - [Survival rate of patients with stomach cancer in Peru, 2009-2010].
AB  - OBJECTIVE: Determine the survival rate of patients diagnosed with stomach cancer
      in 2009-2010 in Peru. METHODS: A retrospective cohort study was conducted of
      patients diagnosed with stomach cancer registered in the National Epidemiological
      Surveillance System (SNVE) of the Directorate General of Epidemiology (DGE) and
      the Register of Vital Statistics (RHV) of the General Office of Statistics and
      Information (OGEI) for the years 2009-2010. RESULTS: 3 568 patients of the SNVE
      were included; 51.5% were men and 48.5% were women; the average age was 63.9
      years; 60.07% were 60 years old or older. It was found that 33.6% had intestinal
      type adenocarcinoma, 18.7% had diffuse type carcinoma, and 4.1% had primary
      gastric lymphoma. The overall survival rate was 29.7 +/- 0.8 months and was
      better for those under 60 years (P = 0.034), for women (P = 0.014) and for
      intestinal type adenocarcinoma (P< 0.001). There was no difference (P = 0.713)
      between the survival rate of gastric lymphomas and adenocarcinomas. In order to
      evaluate mortality, 6 069 patient records from the RHV were included; national
      mortality was 10.3 per 100 000 population; the regions with the highest mortality
      were Huanuco, Huancavelica, and Junin. CONCLUSIONS: The general survival rate was
      29.7 +/- 0.8 months; women, those under 60 years, and patients with intestinal
      type adenocarcinoma had better survival rates. The highest mortality from stomach
      cancer is concentrated in the poorest regions of Peru, where it is probable that
      living conditions facilitate the high communicability of Helicobacter pylori.

PMID- 25988250
TI  - [Adequacy of prenatal care according to maternal characteristics in Brazil].
AB  - OBJECTIVE: To verify the degree of adequacy of prenatal care in Brazil and to
      determine whether it is associated with sociodemographic characteristics of
      women. METHODS: This nationwide hospital-based study was performed with 23 894
      women in 2011 and 2012. Data were obtained from interviews with puerperal women
      and from the prenatal card recording prenatal care appointments. Adequate
      prenatal care was defined as that started no later than the 12th gestational
      week, with performance of at least six consultations (with number of
      consultations adjusted for gestational age at delivery), record in the prenatal
      card of at least one result for each of the recommended routine prenatal tests,
      and guidance regarding the maternity hospital for delivery. Multivariate logistic
      regression was performed to verify the association between maternal
      characteristics and the adequacy of prenatal care. RESULTS: Early onset of
      prenatal care was observed in 53.9% of participants, adequate number of
      consultations in 73.2%, record of at least one of each recommended test in 62.9%,
      guidance regarding maternity hospital in 58.7%, and overall adequate prenatal
      care in 21.6%. Less adequate prenatal care was observed in women who were
      younger, black, multiparous, who did not have a partner, without paid employment,
      having fewer years of formal schooling, belonging to lower socioeconomic classes,
      and living in the North and Northeast of Brazil. After adjustment of maternal
      characteristics, no differences were observed between public or private health
      care services regarding adequacy of prenatal care. CONCLUSIONS: Even though the
      coverage of prenatal care is virtually universal in Brazil, regional and social
      differences in the access and adequacy of care still persist. The implementation
      of strategies to facilitate early access to prenatal care is essential.

PMID- 25988251
TI  - Depression help-seeking attitudes and behaviors among an Internet-based sample of
      Spanish-speaking perinatal women.
AB  - OBJECTIVE: To examine attitudes and beliefs related to help-seeking for
      depression among an international sample of pregnant women, a majority of whom
      were Spanish-speakers residing in Latin America. METHODS: More than 6 000 (n = 6
      672) pregnant women met eligibility criteria and consented to participate between
      15 January 2009-12 August 2011. Of these, 1 760 with a Latino/Hispanic background
      completed a baseline survey as part of a larger study. Group comparisons analyzed
      attitudes and behaviors related to seeking help for depression, while a logistic
      regression was conducted to identify demographic characteristics related to help
      seeking support. RESULTS: Of the participants, three-fourths reported
      experiencing depression during or after their current or past pregnancies. The
      majority of participants did not seek help, and generally reported ambivalence
      about their depressive symptoms and uncertainty as to the helpfulness of others.
      However, 44.8% did seek help, mostly by speaking to family or partners and
      reported feeling fear, shame, and embarrassment about their symptoms. A current
      major depressive episode and an income less than or equal to US$ 10 000 were
      significant predictors of help-seeking behaviors. CONCLUSIONS: Data from this
      study suggest that when feeling sad or depressed, perinatal Latinas tend to seek
      emotional support first from family and friends and may underutilize mental
      health services when needed. The Internet is an effective means for reaching
      perinatal women, especially those in areas of the world where there may be
      barriers to accessing psychological resources.

PMID- 25988252
TI  - [Estimate of the incidence of HIV in the adult population of Paraguay using the
      MoT mathematical model].
AB  - OBJECTIVE: To estimate the incidence of HIV in the adult population of Paraguay
      for 2014 and analyze its distribution and associated uncertainty according to
      risk behavior. METHODS The UNAIDS model was applied according to modes of
      transmission (MoT). Data were obtained from a detailed review of documents
      prepared between 1996 and 2013. Uncertainty of the estimated values was analyzed.
      RESULTS: The estimated incidence for 2014 was 0.091% (3,081 new infections). Both
      the percentage of new infections (74.75%, CI95%: 64.19%-81.47%) and the incidence
      rate per 10,000 population (9,518) were greater in the group of men who have sex
      with men (MSM). The second most affected group was made up of those who have
      stable heterosexual sex (9.9%). Heterosexual transmission accounted for 23% of
      new cases and 8% corresponded to couples (men and women) who engaged in high-risk
      behavior for HIV transmission. Female sex workers and intravenous drug users
      accounted for 1%. CONCLUSIONS: The resulting estimate of the incidence of HIV and
      its distribution among groups at risk is consistent with national-level reports
      and with the characteristics of the MSM population, which accounts for the
      greatest number of cases in the epidemic. Preventive actions should be aimed at
      this group in order to have a significant impact on the course of the epidemic in
      the country. Furthermore, it is recommended that preventive activities aimed at
      stable couples in at-risk groups and the general population be expanded and
      strengthened.

PMID- 25988253
TI  - A systematic review of nursing research priorities on health system and services
      in the Americas.
AB  - OBJECTIVE: To systematically review literature on priorities in nursing research
      on health systems and services in the Region of the Americas as a step toward
      developing a nursing research agenda that will advance the Regional Strategy for
      Universal Access to Health and Universal Health Coverage. METHOD: This was a
      systematic review of the literature available from the following databases: Web
      of Science, PubMed, LILACS, and Google. Documents considered were published in
      2008-2014; in English, Spanish, or Portuguese; and addressed the topic in the
      Region of the Americas. The documents selected had their priority-setting process
      evaluated according to the "nine common themes for good practice in health
      research priorities." A content analysis collected all study questions and
      topics, and sorted them by category and subcategory. RESULTS: Of 185 full-text
      articles/documents that were assessed for eligibility, 23 were selected: 12 were
      from peer-reviewed journals; 6 from nursing publications; 4 from Ministries of
      Health; and 1 from an international organization. Journal publications had
      stronger methodological rigor; the majority did not present a clear
      implementation or evaluation plan. After compiling the 444 documents' study
      questions and topics, the content analysis resulted in a document with 5
      categories and 16 subcategories regarding nursing research priorities on health
      systems and services. CONCLUSIONS: Research priority-setting is a highly
      important process for health services improvement and resources optimization, but
      implementation and evaluation plans are rarely included. The resulting document
      will serve as basis for the development of a new nursing research agenda focused
      on health systems and services, and shaped to advance universal health coverage
      and universal access to health.

PMID- 25988254
TI  - [Differences between the 2013 and 2014 hypertension guidelines.: Position of the
      Central American and Caribbean Society for Hypertension and Cardiovascular
      Prevention].
AB  - Between the end of 2013 and the beginning of 2014 the most internationally
      influential hypertension guidelines were published. Although there are no major
      differences between them, there are discrepancies that can have an impact on
      treatment and prognosis for individuals with hypertension. This article analyzes
      the main controversial elements in the guides and presents the recommendations of
      the Sociedad Centroamericana y del Caribe de Hipertension y Prevencion
      Cardiovascular (Caribbean Society for Hypertension and Cardiovascular
      Prevention). The main differences are found a) in the categorization of
      prehypertension, b) in the use of global cardiovascular risk in the decision to
      begin antihypertensive treatment, c) in the validity of beta-blockers as first
      line drugs in treating uncomplicated hypertension, and d) the increase in the
      therapeutic goal of maintaining values between < 140/90 and < 150/90 mmHg in
      patients over 60 years of age with no history of diabetes or chronic kidney
      disease. All the factors in favor of and against accepting each of these four
      controversial criteria are analyzed critically and the observations made by the
      Society are included. The conclusion is that there are pros and cons for all
      controversial elements in the hypertension guides. However, the weight of the
      evidence and clinical judgment favor subdividing prehypertension into stages I
      and II, seeking a therapeutic goal of maintaining systolic blood pressure below
      140 mmHg in all the hypertensive patients under 80 years of age, retaining beta
      blockers as first-line drugs in uncomplicated hypertension, and not delaying the
      start of drug treatment for hypertension stage I with low global cardiovascular
      risk. Finally, seven recommendations by the Society based on the analysis are
      included. 

PMID- 25988255
TI  - Congenital rubella syndrome: a matter of concern.
AB  - Congenital rubella syndrome (CRS), an important cause of severe birth defects,
      remains a public health problem in a significant number of countries. Therefore,
      global health experts encourage use of rubella vaccination, with the primary aim
      of preventing CRS. While large-scale rubella vaccination during the last decade
      has drastically reduced or eliminated both the virus and CRS in Europe and the
      Americas, many countries in Africa, South-East Asia, the Eastern Mediterranean,
      and the Western Pacific have not yet incorporated any type of rubella-containing
      vaccine into their immunization schedule. As a result, through travel and
      migration, rubella has been imported into countries that had successfully
      eliminated the virus, leading to outbreaks and the reestablishment of endemic
      transmission. The objective of this study was to identify the key factors
      required for CRS elimination (prevalence reduction, vaccination strategies, and
      surveillance methods) by reviewing publications in PubMed on rubella and CRS
      (systematic reviews, country experiences, and position papers from the World
      Health Organization (WHO) and other intergovernmental organizations). Based on
      the results of the review, to eliminate rubella and CRS in endemic areas and
      reduce re-emergence in previously disease-free areas, all countries should carry
      out two types of mass rubella vaccination campaigns: 1) one single mass national
      immunization campaign targeting all men and women 5-39+ years old (with the upper
      age limit depending on the year in which the rubella-containing vaccine was
      introduced and the epidemiology of rubella in the country) and 2) incorporation
      of an rubella-containing vaccine in routine childhood immunization programs,
      including regular vaccination campaigns for 12-month-olds and measles follow-up
      campaigns. In addition to mass rubella immunization campaigns and routine
      childhood vaccination programs, the following measures should be taken to help
      fight rubella and CRS: 1) surveillance of the number of susceptible women of
      childbearing age, and the emergence of imported cases; 2) coverage of susceptible
      populations with "second-chance" ("catch-up") campaigns (vaccination of older
      children and adults who may have missed earlier immunization programs); 3) rapid
      response to outbreaks; 4) strengthening of CRS surveillance; 5) involvement of
      the private sector in awareness and vaccination campaigns; and 6) reduction of
      the number of false-positive laboratory test results. 

PMID- 25988256
TI  - [Self-management: a comprehensive approach to management of chronic conditions].
AB  - For both clinical and economic reasons, the increasing number of persons living
      with chronic conditions represents a public health issue of growing importance.
      Emphasizing patient responsibility, and acting in concert with the provider
      community, self-management represents a promising strategy for treating chronic
      conditions-moving beyond education to teaching individuals to actively identify
      challenges and solve problems associated with their illness. Self-management also
      shows potential as an effective paradigm across the prevention spectrum (primary,
      secondary, and tertiary) by establishing a pattern for health early in life and
      providing strategies for mitigating illness and managing it in later life. We
      suggest ways to advance research methods and practical applications of self
      management as steps in its future development and implementation. 

PMID- 25988258
TI  - Nutrient Loading through Submarine Groundwater Discharge and Phytoplankton Growth
      in Monterey Bay, CA.
AB  - We quantified groundwater discharge and associated nutrient fluxes to Monterey
      Bay, California, during the wet and dry seasons using excess (224)Ra as a tracer.
      Bioassay incubation experiments were conducted to document the response of bloom
      forming phytoplankton to submarine groundwater discharge (SGD) input. Our data
      indicate that the high nutrient content (nitrate and silica) in groundwater can
      stimulate the growth of bloom-forming phytoplankton. The elevated concentrations
      of nitrate in groundwater around Monterey Bay are consistent with agriculture,
      landfill, and rural housing, which are the primary land-uses in the area
      surrounding the study site. These findings indicate that SGD acts as a continual
      source of nutrients that can feed bloom-forming phytoplankton at our study site,
      constituting a nonpoint source of anthropogenic nutrients to Monterey Bay. 

PMID- 25988257
TI  - Heparin affinity purification of extracellular vesicles.
AB  - Extracellular vesicles (EVs) are lipid membrane vesicles released by cells. They
      carry active biomolecules including DNA, RNA, and protein which can be
      transferred to recipient cells. Isolation and purification of EVs from culture
      cell media and biofluids is still a major challenge. The most widely used
      isolation method is ultracentrifugation (UC) which requires expensive equipment
      and only partially purifies EVs. Previously we have shown that heparin blocks EV
      uptake in cells, supporting a direct EV-heparin interaction. Here we show that
      EVs can be purified from cell culture media and human plasma using
      ultrafiltration (UF) followed by heparin-affinity beads. UF/heparin-purified EVs
      from cell culture displayed the EV marker Alix, contained a diverse RNA profile,
      had lower levels of protein contamination, and were functional at binding to and
      uptake into cells. RNA yield was similar for EVs isolated by UC. We were able to
      detect mRNAs in plasma samples with comparable levels to UC samples. In
      conclusion, we have discovered a simple, scalable, and effective method to purify
      EVs taking advantage of their heparin affinity. 

PMID- 25988260
TI  - Do deposit-feeders compete? Isotopic niche analysis of an invasion in a species
      poor system.
AB  - Successful establishment of invasive species is often related to the existence of
      vacant niches. Competition occurs when invaders use the same limiting resources
      as members of the recipient community, which will be reflected in some overlap of
      their trophic niches. The concept of isotopic niche has been used to study
      trophic niche partitioning among species. Here, we present a two-year field study
      comparing isotopic niches of the deposit-feeding community in a naturally species
      poor system. The isotopic niche analyses showed no overlap between a recent
      polychaete invader and any of the native species suggesting that it has occupied
      a vacant niche. Its narrow isotopic niche suggests specialized feeding, however,
      the high delta(15)N values compared to natives are most likely due to isotope
      fractionation effects related to nitrogen recycling and a mismatch between
      biological stoichiometry of the polychaete and the sediment nitrogen content.
      Notably, highly overlapping isotopic niches were inferred for the native species,
      which is surprising in a food-limited system. Therefore, our results demonstrate
      that invaders may broaden the community trophic diversity and enhance resource
      utilization, but also raise questions about the congruence between trophic and
      isotopic niche concepts and call for careful examination of assumptions
      underlying isotopic niche interpretation. 

PMID- 25988259
TI  - An inactive geminin mutant that binds cdt1.
AB  - The initiation of DNA replication is tightly regulated in order to ensure that
      the genome duplicates only once per cell cycle. In vertebrate cells, the unstable
      regulatory protein Geminin prevents a second round of DNA replication by
      inhibiting the essential replication factor Cdt1. Cdt1 recruits mini-chromosome
      maintenance complex (MCM2-7), the replication helicase, into the pre-replication
      complex (pre-RC) at origins of DNA replication. The mechanism by which Geminin
      inhibits MCM2-7 loading by Cdt1 is incompletely understood. The conventional
      model is that Geminin sterically hinders a direct physical interaction between
      Cdt1 and MCM2-7. Here, we describe an inactive missense mutant of Geminin,
      GemininAWA, which binds to Cdt1 with normal affinity yet is completely inactive
      as a replication inhibitor even when added in vast excess. In fact, GemininAWA
      can compete with GemininWT for binding to Cdt1 and prevent it from inhibiting DNA
      replication. GemininAWA does not inhibit the loading of MCM2-7 onto DNA in vivo,
      and in the presence of GemininAWA, nuclear DNA is massively over-replicated
      within a single S phase. We conclude that Geminin does not inhibit MCM loading by
      simple steric interference with a Cdt1-MCM2-7 interaction but instead works by a
      non-steric mechanism, possibly by inhibiting the histone acetyltransferase HBO1. 

PMID- 25988261
TI  - The Influence of Single-Dose and Short-Term Administration of Quercetin on the
      Pharmacokinetics of Midazolam in Humans.
AB  - Quercetin is a plant flavonol that is available from both daily diet and
      nutraceuticals. To investigate the effect of acute and short-term intake of high
      dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5
      mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1
      week supplementation with 1500 mg quercetin daily. A substudy was performed in
      three subjects to explore the impact of repeated quercetin intake on
      intravenously administered midazolam. Coadministration with a single dose of
      quercetin did not significantly alter the pharmacokinetics of midazolam and its
      1'-hydroxymetabolite, but following short-term quercetin intake, there was a
      trend to reduced midazolam exposure (geometric mean ratio of test-control area
      under the plasma concentration-time curve (AUC0-infinity ): 0.82; 90% confidence
      interval: 0.61-1.10) and midazolam-metabolite AUC0-infinity ratios were decreased
      by 9.7%-47.6% from control in seven subjects. The tendency was opposite when
      midazolam was given intravenously. We conclude that a single dose of quercetin
      would not provoke any toxic adverse events when coadministered with midazolam,
      whereas repeated quercetin intake can reduce systemic exposure to the orally
      given drug by increasing its CYP3A-catalyzed metabolism. As the effect deviated
      after intravenous drug administration, different mechanisms of interaction may be
      involved at the intestinal site compared with the liver.

PMID- 25988263
TI  - Investigating Conversational Dynamics: Interactive Alignment, Interpersonal
      Synergy, and Collective Task Performance.
AB  - This study investigates interpersonal processes underlying dialog by comparing
      two approaches, interactive alignment and interpersonal synergy, and assesses how
      they predict collective performance in a joint task. While the interactive
      alignment approach highlights imitative patterns between interlocutors, the
      synergy approach points to structural organization at the level of the
      interaction-such as complementary patterns straddling speech turns and
      interlocutors. We develop a general, quantitative method to assess lexical,
      prosodic, and speech/pause patterns related to the two approaches and their
      impact on collective performance in a corpus of task-oriented conversations. The
      results show statistical presence of patterns relevant for both approaches.
      However, synergetic aspects of dialog provide the best statistical predictors of
      collective performance and adding aspects of the alignment approach does not
      improve the model. This suggests that structural organization at the level of the
      interaction plays a crucial role in task-oriented conversations, possibly
      constraining and integrating processes related to alignment. 

PMID- 25988262
TI  - Radiation Doses in Consecutive CT Examinations from Five University of California
      Medical Centers.
AB  - PURPOSE: To summarize data on computed tomographic (CT) radiation doses collected
      from consecutive CT examinations performed at 12 facilities that can contribute
      to the creation of reference levels. MATERIALS AND METHODS: The study was
      approved by the institutional review boards of the collaborating institutions and
      was compliant with HIPAA. Radiation dose metrics were prospectively and
      electronically collected from 199 656 consecutive CT examinations in 83 181
      adults and 3871 consecutive CT examinations in 2609 children at the five
      University of California medical centers during 2013. The median volume CT dose
      index (CTDIvol), dose-length product (DLP), and effective dose, along with the
      interquartile range (IQR), were calculated separately for adults and children and
      stratified according to anatomic region. Distributions for DLP and effective dose
      are reported for single-phase examinations, multiphase examinations, and all
      examinations. RESULTS: For adults, the median CTDIvol was 50 mGy (IQR, 37-62 mGy)
      for the head, 12 mGy (IQR, 7-17 mGy) for the chest, and 12 mGy (IQR, 8-17 mGy)
      for the abdomen. The median DLPs for single-phase, multiphase, and all
      examinations, respectively, were as follows: head, 880 mGy . cm (IQR, 640-1120
      mGy . cm), 1550 mGy . cm (IQR, 1150-2130 mGy . cm), and 960 mGy . cm (IQR, 690
      1300 mGy . cm); chest, 420 mGy . cm (IQR, 260-610 mGy . cm), 880 mGy . cm (IQR,
      570-1430 mGy . cm), and 550 mGy . cm (IQR 320-830 mGy . cm); and abdomen, 580 mGy
      . cm (IQR, 360-860 mGy . cm), 1220 mGy . cm (IQR, 850-1790 mGy . cm), and 960 mGy
      . cm (IQR, 600-1460 mGy . cm). Median effective doses for single-phase,
      multiphase, and all examinations, respectively, were as follows: head, 2 mSv
      (IQR, 1-3 mSv), 4 mSv (IQR, 3-8 mSv), and 2 mSv (IQR, 2-3 mSv); chest, 9 mSv
      (IQR, 5-13 mSv), 18 mSv (IQR, 12-29 mSv), and 11 mSv (IQR, 6-18 mSv); and
      abdomen, 10 mSv (IQR, 6-16 mSv), 22 mSv (IQR, 15-32 mSv), and 17 mSv (IQR, 11-26
      mSv). In general, values for children were approximately 50% those for adults in
      the head and 25% those for adults in the chest and abdomen. CONCLUSION: These
      summary dose data provide a starting point for institutional evaluation of CT
      radiation doses.

PMID- 25988264
TI  - Spatial and spatiotemporal variation in metapopulation structure affects
      population dynamics in a passively dispersing arthropod.
AB  - The spatial and temporal variation in the availability of suitable habitat within
      metapopulations determines colonization-extinction events, regulates local
      population sizes and eventually affects local population and metapopulation
      stability. Insights into the impact of such a spatiotemporal variation on the
      local population and metapopulation dynamics are principally derived from
      classical metapopulation theory and have not been experimentally validated. By
      manipulating spatial structure in artificial metapopulations of the spider mite
      Tetranychus urticae, we test to which degree spatial (mainland-island
      metapopulations) and spatiotemporal variation (classical metapopulations) in
      habitat availability affects the dynamics of the metapopulations relative to
      systems where habitat is constantly available in time and space (patchy
      metapopulations). Our experiment demonstrates that (i) spatial variation in
      habitat availability decreases variance in metapopulation size and decreases
      density-dependent dispersal at the metapopulation level, while (ii)
      spatiotemporal variation in habitat availability increases patch extinction
      rates, decreases local population and metapopulation sizes and decreases density
      dependence in population growth rates. We found dispersal to be negatively
      density dependent and overall low in the spatial variable mainland-island
      metapopulation. This demographic variation subsequently impacts local and
      regional population dynamics and determines patterns of metapopulation stability.
      Both local and metapopulation-level variabilities are minimized in mainland
      island metapopulations relative to classical and patchy ones. 

PMID- 25988265
TI  - An Intervention To Enhance the Food Environment in Public Recreation and Sport
      Settings: A Natural Experiment in British Columbia, Canada.
AB  - BACKGROUND: Publicly funded recreation and sports facilities provide children
      with access to affordable physical activities, although they often have unhealthy
      food environments that may increase child obesity risk. This study evaluated the
      impact of a capacity-building intervention (Healthy Food and Beverage Sales;
      HFBS) on organizational capacity for providing healthy food environments, health
      of vending machine products, and food policy development in recreation and sport
      facilities in British Columbia, Canada. METHODS: Twenty-one HFBS communities
      received training, resources, and technical support to improve their food
      environment over 8 months in 2009-2010, whereas 23 comparison communities did
      not. Communities self-reported organizational capacity, food policies, and
      audited vending machine products at baseline and follow-up. Repeated-measures
      analysis of variance evaluated intervention impact. RESULTS: Intervention and
      comparison communities reported higher organizational capacity at follow-up;
      however, improvements were greater in HFBS communities (p<0.001). Healthy vending
      products increased from 11% to 15% (p<0.05), whereas unhealthy products declined
      from 56% to 46% (p<0.05) in HFBS communities, with no changes in comparison
      communities. At baseline 10% of HFBS communities reported having a healthy food
      policy, whereas 48% reported one at follow-up. No comparison communities had food
      policies. CONCLUSIONS: This is the first large, controlled study to examine the
      impact of an intervention to improve recreation and sport facility food
      environments. HFBS communities increased their self-rated capacity to provide
      healthy foods, healthy vending product offerings, and food policies to a greater
      extent than comparison communities. Recreation and sport settings are a priority
      setting for supporting healthy dietary behaviors among children.

PMID- 25988267
TI  - Effects of Polytypism on Optical Properties and Band Structure of Individual
      Ga(N)P Nanowires from Correlative Spatially Resolved Structural and Optical
      Studies.
AB  - III-V semiconductor nanowires (NWs) have gained significant interest as building
      blocks in novel nanoscale devices. The one-dimensional (1D) nanostructure
      architecture allows one to extend band structure engineering beyond quantum
      confinement effects by utilizing formation of different crystal phases that are
      thermodynamically unfavorable in bulk materials. It is therefore of crucial
      importance to understand the influence of variations in the NWs crystal structure
      on their fundamental physical properties. In this work we investigate effects of
      structural polytypism on the optical properties of gallium phosphide and GaP/GaNP
      core/shell NW structures by a correlative investigation on the structural and
      optical properties of individual NWs. The former is monitored by transmission
      electron microscopy, whereas the latter is studied via cathodoluminescence (CL)
      mapping. It is found that structural defects, such as rotational twins in zinc
      blende (ZB) GaNP, have detrimental effects on light emission intensity at low
      temperatures by promoting nonradiative recombination processes. On the other
      hand, formation of the wurtzite (WZ) phase does not notably affect the CL
      intensity neither in GaP nor in the GaNP alloy. This suggests that zone folding
      in WZ GaP does not enhance its radiative efficiency, consistent with theoretical
      predictions. We also show that the change in the lattice structure have
      negligible effects on the bandgap energies of the GaNP alloys, at least within
      the range of the investigated nitrogen compositions of <2%. Both WZ and ZB GaNP
      are found to have a significantly higher efficiency of radiative recombination as
      compared with that in parental GaP, promising for potential applications of GaNP
      NWs as efficient nanoscale light emitters within the desirable amber-red spectral
      range. 

PMID- 25988269
TI  - Substance flow analysis of phosphorus within New Zealand and comparison with
      other countries.
AB  - Phosphorus (P) is an essential and non-renewable resource that is estimated to be
      depleted within the next 70-140 years. Increasing P scarcity and environmental
      pollution requires the development of a proper P management system. One
      fundamental step is to understand how P flows within society. Thus, a substance
      flow analysis (SFA) of P was conducted to distinguish and quantify different P
      flows within New Zealand, and principal component analysis (PCA) was used to show
      where the P flow in New Zealand was significantly different from the most
      efficient P utilization countries. Aside from having low P recovery, New Zealand
      imports a significant amount of P, while re-exporting a much smaller fraction of
      it compared with other countries, resulting in a high accumulation. The SFA
      analysis showed that although diffuse sources of P pollution pose a greater
      environmental risk to water bodies, promoting P recovery from point sources of
      pollution, such as from waste treatment facilities and landfill sites, would
      still improve the P management efficiency in New Zealand, which could decrease
      the annual P rock imports by 20%.

PMID- 25988268
TI  - Tickborne relapsing fever in southern Iran, 2011-2013.

PMID- 25988270
TI  - Day-to-Day Changes of Auricular Point Acupressure to Manage Chronic Low Back
      Pain: A 29-day Randomized Controlled Study.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of a 4-week
      auricular point acupressure (APA) treatment on chronic low back pain (CLBP)
      outcomes and examine the day-to-day variability of CLBP in individuals receiving
      APA for CLBP over 29 days. DESIGN: This was a prospective, randomized controlled
      trial (RCT). Data were collected at baseline, during each of the four office
      visits for APA treatment, after the completion of the 4-week intervention, and 1
      month after the last treatment. A daily diary was given to each participant to
      record his or her APA practices, analgesic use, and pain intensity.
      INTERVENTIONS: APA was used to manage CLBP. The participants received one APA
      treatment per week for 4 weeks. PATIENTS AND SETTING: Sixty-one participants with
      CLBP were randomized into either a real APA or sham APA treatment group.
      Participants were recruited from primary care offices and clinics or through the
      Research Participant Registry at the University of Pittsburgh. RESULTS: Among
      participants in the real APA group, a 30% reduction of worst pain was exhibited
      after the first day of APA treatment, and continuous reduction in pain (44%) was
      reported by the completion of the 4-week APA. This magnitude of pain reduction
      reached the clinically significant level of improvement reported in other
      clinical trials of chronic pain therapies. Analgesic use by participants in the
      real APA group also was reduced compared with use by participants in the sham
      group. CONCLUSION: This study shows that APA is a promising pain management
      strategy that is not invasive and can be self-managed by participants for CLBP.
      Given the day-to-day fluctuation in ratings, the tighter ecologic assessment of
      pain scores and other treatment parameters are an important pragmatic aspect of
      the design of chronic pain studies.

PMID- 25988271
TI  - Diameter of main tumor feeding artery of a hepatocellular carcinoma: Measurement
      at the entry site into the nodule.
AB  - AIM: To measure the diameter of the main tumor feeding artery (TFA) of a
      hepatocellular carcinoma (HCC) nodule at the entry site into the nodule. METHODS:
      Fifty-seven HCC nodules in 43 patients were analyzed using a 3-D workstation and
      picture archiving system (PACS). TFA was defined as an artery connected to a HCC
      nodule on catheter-assisted multidetector computed tomography angiography
      (CAMDCTA). The entry site of the main TFA into the nodule was identified on
      CAMDCTA, and the corresponding portion was measured on digital angiography (DA)
      or digital subtracted angiography (DSA). The measuring scale of the PACS was
      calibrated using the platinum tip of microballoon catheters 0.68 mm in diameter.
      We investigated the relationship between diameters of the nodule and its main
      TFA. RESULTS: The diameters of the nodule and its main TFA ranged 7-63 mm (20.3
      +/- 12.7) and 0.12-1.79 mm (0.41 +/- 0.32), respectively. Simple regression
      analysis revealed a relationship between diameters of the nodule and its main TFA
      (P < 0.0001). The diameter of the main TFA was less than 1 mm in 53 of 57 nodules
      (93.0%), and less than 0.5 mm in 42 (73.7%). CONCLUSION: The diameter of main TFA
      was thicker in the larger nodule. The size of commercially available porous
      gelatin particles (1 or 2 mm in diameter) seems too large for embolization of
      most of HCC nodules.

PMID- 25988272
TI  - A proposed approach to systematically identify and monitor the corporate
      political activity of the food industry with respect to public health using
      publicly available information.
AB  - Unhealthy diets represent one of the major risk factors for non-communicable
      diseases. There is currently a risk that the political influence of the food
      industry results in public health policies that do not adequately balance public
      and commercial interests. This paper aims to develop a framework for categorizing
      the corporate political activity of the food industry with respect to public
      health and proposes an approach to systematically identify and monitor it. The
      proposed framework includes six strategies used by the food industry to influence
      public health policies and outcomes: information and messaging; financial
      incentive; constituency building; legal; policy substitution; opposition
      fragmentation and destabilization. The corporate political activity of the food
      industry could be identified and monitored through publicly available data
      sourced from the industry itself, governments, the media and other sources. Steps
      for country-level monitoring include identification of key food industry actors
      and related sources of information, followed by systematic data collection and
      analysis of relevant documents, using the proposed framework as a basis for
      classification of results. The proposed monitoring approach should be pilot
      tested in different countries as part of efforts to increase the transparency and
      accountability of the food industry. This approach has the potential to help
      redress any imbalance of interests and thereby contribute to the prevention and
      control of non-communicable diseases. 

PMID- 25988273
TI  - Contribution of Clostridium difficile infection to the development of lower
      gastrointestinal adverse events during autologous stem cell transplantation.
AB  - BACKGROUND: Lower gastrointestinal (GI) adverse events (LGAE) are common
      afflictions of patients undergoing stem cell transplantation (SCT).
      Unfortunately, the pathophysiology remains poorly characterized. Emerging data
      suggest a prominent role of intestinal microbiota; however, contributions of
      pathogenic gut microbiota such as Clostridium difficile are not well defined. We
      performed a genome-wide association study (GWAS) to investigate clinical and
      genetic factors associated with development of LGAE. METHODS: A total of 972
      patients undergoing autologous SCT were graded for LGAE based on Common
      Terminology Criteria for Adverse Events (v 4.0). Germline DNA material was
      obtained from leukapharesis products and genotyped using Illumina((r)) Whole
      Genome Genotyping Infinium chemistry and HumanOmni1-Quad Bead chips containing
      over 1.1 million single nucleotide polymorphisms (SNPs) (Illumina, San Diego,
      California, USA). Statistical models incorporating clinical factors, genetic
      factors, and a combination of clinical plus genetic factors were utilized to
      compare patients who developed severe LGAE (grade 2 or above) and others.
      RESULTS: Among 972 patients, 459 (47.2%) developed severe LGAE. Baseline
      hemoglobin and hematocrit, estimated glomerular filtration rate, beta2
      microglobulin, protocol type, and C. difficile infection (CDI) were associated
      with severe LGAE on univariate analysis, Genomic comparisons between groups did
      not reveal any SNPs associated with severe LGAE and neither did incorporation of
      genetic factors into the clinical model. In addition, 11 candidate SNPs
      associated with upper GI mucositis were evaluated, alongside clinical factors in
      a multivariate model. Only CDI was found to be associated with severe LGAE in all
      models. CONCLUSION: CDI is a prominent factor in the development of LGAE in
      patients undergoing autologous SCT.

PMID- 25988275
TI  - Therapeutic alliance in mental health nursing: an evolutionary concept analysis.
AB  - The concept of therapeutic alliance is relevant in contemporary mental health
      care, as the consumer-led recovery movement promotes the development of
      collaborative relationships, and is focussed on the consumer's individual concept
      of wellbeing. An evolutionary concept analysis was undertaken to establish a
      contemporary interpretation of therapeutic alliance for mental health nursing.
      The CINAHL, Scopus and PsycINFO databases were searched for articles (n = 322),
      with 52 deemed appropriate for analysis. Therapeutic alliance is characterised by
      mutual partnerships between nurses and consumers, and is dependent on a
      humanistic healthcare culture. Therapeutic alliance is associated with enhanced
      consumer outcomes and experiences with care. 

PMID- 25988274
TI  - Visualization and Interpretation of Support Vector Machine Activity Predictions.
AB  - Support vector machines (SVMs) are among the preferred machine learning
      algorithms for virtual compound screening and activity prediction because of
      their frequently observed high performance levels. However, a well-known
      conundrum of SVMs (and other supervised learning methods) is the black box
      character of their predictions, which makes it difficult to understand why models
      succeed or fail. Herein we introduce an approach to rationalize the performance
      of SVM models based upon the Tanimoto kernel compared with the linear kernel.
      Model comparison and interpretation are facilitated by a visualization technique,
      making it possible to identify descriptor features that determine compound
      activity predictions. An implementation of the methodology has been made freely
      available. 

PMID- 25988276
TI  - Reliability of manikin-based studies: an evaluation of manikin characteristics
      and their impact on measurements of ventilatory variables.
AB  - Findings from manikin-based studies on ventilation are commonly directly
      extrapolated to clinical practice. The aim of this study was to determine how the
      use of manikins affects measurements of ventilatory variables. We connected a
      lung simulator to a manikin, which was then ventilated at different inspiratory
      flows. We defined three experimental models to compare measurements of
      ventilatory variables between the mechanical ventilator and the lung simulator.
      Even when no leakage occurred, significant tidal volume deviations were observed;
      from a mean (SD) of 21 (2) ml to 49 (9) ml, and from 40 (4) ml to 88 (5) ml for
      invasive and non-invasive ventilation, respectively (p < 0.001). Significant peak
      pressure deviations from 0.7 (0.1) cmH2 O to 10.6 (0.3) cmH2 O were also recorded
      during non-invasive ventilation (p < 0.001). Evaluation of manikin resistance and
      airway dead space may be essential to limit study bias. We suggest a
      recalibration of the recorded data if comparisons are made between different
      tests performed at different inspiratory flows.

PMID- 25988277
TI  - Bacteriology of deep neck infections: analysis of 634 patients.
AB  - BACKGROUND: The aim of this study was to review the bacteriology of deep neck
      infections (DNI) and identify the factors that influence the incidence of
      causative bacteria. METHODS: A retrospective analysis of 634 patients with DNI
      was performed. Statistical analysis was used to compare the incidence of common
      pathogens in various conditions such as age of the patients, aetiology and
      associated diabetes mellitus. RESULTS: Bacteria were isolated in 514 cultures
      (81%). Aerobic bacteria were isolated from 246 cultures (39%) and anaerobic
      bacteria from 61 cultures (10%). Both aerobic and anaerobic bacteria were
      isolated from 207 cultures (32%). The most common aerobic bacteria were
      Streptococcus pyogenes (41%) and Staphylococcus aureus (32%). The most common
      anaerobic bacteria were Peptostreptococcus species (28%), followed by Prevotela
      species (8%) and Proprionibacterium species (7%). The incidence of anaerobic
      bacteria was higher in adults, in patients with infections of dental origin and
      in non-diabetic patients. CONCLUSIONS: The bacteriology of DNI is polymicrobial,
      including both aerobic and anaerobic bacteria. The incidence of anaerobic
      bacteria is higher in adults, in patients with infections of dental origin and in
      non-diabetic patients.

PMID- 25988279
TI  - Targeting of AIDS related encephalopathy using phenylalanine anchored lipidic
      nanocarrier.
AB  - Transport of the anti-HIV agents across the blood-brain barrier (BBB) is a
      prerequisite to treat acquired immunodeficiency syndrome (AIDS) related
      encephalopathy. In the present study, we explored facilitated transport of
      efavirenz (EFV, a non-nucleoside reverse transcriptase inhibitor) across BBB
      using phenylalanine anchored solid lipid nanoparticles (PA-SLN). PA (amino acid
      micro-nutrient) was used as a ligand which facilitated carrier mediated transport
      (CMT) via l-amino acid transporter i.e. LAT1 to traverse BBB. PA was coupled to
      SLN via amide linkage using carbodiimide chemistry and coupling was confirmed by
      comparative infrared spectroscopic analysis. SLNs (SLN and PA-SLN) were
      nanometric in size (around 150nm) and possessed good entrapment efficiency
      (around 70%). In vitro drug release revealed controlled release pattern for more
      than 24h. In vivo studies showed 2-3-folds and 7-8-folds accumulation of PA-SLN
      in brain as compared to SLN and EFV, respectively. Further, transcytosis studies
      confirmed capability of PA-SLN to cross BBB i.e. 10-fold higher transcytosis
      potential as compared to EFV. Fluorescence microscopic imaging reassured enhanced
      brain localization of PA-SLN. Thus, PA-SLN improved the EFV bioavailability and
      maintained therapeutic levels in the brain for an extended period of time that
      can result in significant eradication of the viral load therein. Such nutrient
      mediated drug targeting could bring forth advances in biocompatible and
      biodegradable drug delivery systems. 

PMID- 25988278
TI  - Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic
      Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A
      Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - OBJECTIVE: Vitamin D has an important immunomodulatory effect, but there are no
      trials that directly address the boosting of serum levels of 25-hydroxyvitamin D
      (25[OH]D) in juvenile-onset systemic lupus erythematosus (SLE). The aim of this
      study was to evaluate the effect of vitamin D supplementation on disease activity
      and fatigue in juvenile-onset SLE. METHODS: This study was a randomized, double
      blind, placebo-controlled, 24-week trial. Forty juvenile-onset SLE patients were
      randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (juvenile-onset
      SLE-VitD) or placebo (juvenile-onset SLE-PL). Medications remained stable
      throughout the study. Serum levels of 25(OH)D were measured using
      radioimmunoassay. Disease activity was assessed using the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus
      Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue
      Severity Scale (K-FSS). RESULTS: At baseline, groups were similar regarding age,
      body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive
      drugs, SLEDAI, ECLAM, K-FSS, and levels of 25(OH)D. After 24 weeks, the mean
      level of 25(OH)D was higher in the juvenile-onset SLE-VitD group than in the
      juvenile-onset SLE-PL group (P < 0.001). At the end of the intervention, a
      significant improvement in SLEDAI (P = 0.010) and in ECLAM (P = 0.006) was
      observed in the juvenile-onset SLE-VitD group compared to the juvenile-onset SLE
      PL group. Regarding fatigue evaluation, a reduction of fatigue related to social
      life score was found in the juvenile-onset SLE-VitD group compared to the
      juvenile-onset SLE-PL group (P = 0.008). Cholecalciferol was well tolerated with
      no serious adverse events. CONCLUSION: This study suggests that cholecalciferol
      supplementation for 24 weeks is effective in decreasing disease activity and
      improving fatigue in juvenile-onset SLE patients.

PMID- 25988280
TI  - Bromocriptine tablet of self-microemulsifying system adsorbed onto porous carrier
      to stimulate lipoproteins secretion for brain cellular uptake.
AB  - Both low solubility and high hepatic metabolism cause low oral bioavailability of
      bromocriptine mesylate (BM) leading to very low drug amount in brain. Self
      microemulsion (SME) tablets were developed to improve solubility, stimulate
      lipoprotein synthesis to promote lymphatic transport, avoid hepatic metabolism
      and target drug to brain. SME liquid containing castor oil, Tween((r)) 80 and
      Cremophor((r)) EL was prepared and then adsorbed onto solid carries,
      Aerosil((r))200, Aeroperl((r))300 or NeusilinUS2((r)), yielding SME powders. The
      optimal ratios of SME liquid to carriers determined from flowability and scanning
      electron photomicrographs before tableting were 1.5:1, 2:1 and 2.5:1 for
      Aerosil((r))200, Aeroperl((r))300 and NeusilinUS2((r)), respectively. Only
      Aeroperl((r))300 SME tablet had comparable dissolution to BM commercial tablet.
      From in vitro study in Caco-2 cells, fluorescein loaded SME tablet showed higher
      uptake than fluorescein loaded in either oil or surfactant. Although
      significantly lower amount of drug was permeated from SME tablet than from
      commercial tablet, higher drug uptake was obviously observed (P<0.05). In
      addition, higher lipoprotein synthesis expressing as content of apolipoprotein B
      (apo-B) found in secreted chylomicron resulted in higher drug uptake in co
      culture of brain endothelial cells (bEnd.3) and astrocytes (CTX TNA2) from drug
      loaded SME tablet when compared to commercial tablet (P<0.05) due to binding of
      apo-B to LDL receptors expressed on the surface of endothelial cells. Therefore,
      tablet of SME adsorbed onto porous carrier potentially delivered BM to brain via
      lymphatic transport by increasing the lipoprotein synthesis. 

PMID- 25988281
TI  - Controlled delivery of bPEI-niclosamide complexes by PEO nanofibers and
      evaluation of its anti-neoplastic potentials.
AB  - Since the turn of the 21st century, nanofiber based drug delivery systems have
      evolved drastically to attain controlled and sustained delivery of various
      bioactive molecules. In spite of such efforts, the tangible interface existing
      between the target cells and the drug molecules could not be narrowed down. This
      drawback has been overcome in this work by realizing nanofiber based scaffold for
      delivery of polymer-drug complexes rather than just the drug. In course with
      this, in the present study a differentially cross-linkable bPEI-PEO (branched
      polyethylenimine-poly(ethylene oxide)) based nanofiber is fabricated for tunable
      delivery of bPEI-niclosamide complexes. Hydrophilic bPEI-niclosamide complexes
      are pre-synthesized and stabilized by crosslinking agent, which were then
      incorporated into bPEI-PEO nanofibers by electrospinning. The niclosamide loaded
      nanofibers by virtue of bPEI moieties presence were then cross-linked to
      different degrees which in turn altered bPEI-niclosamide release profile. The
      release kinetics of bPEI-niclosamide complexes from nanofibers was elucidated
      further by Korsmeyer-Peppas model. Apart from this, the versatile nature of bPEI
      PEO nanofibers was also validated for different drug loading concentration and
      extent of crosslinking. The fibers antitumor efficacy was then assessed against
      A549 (Non-small cell lung cancer cells) and U-87 MG (glioblastoma cells) at two
      different time points (at 48h and 96h) in order to realize the importance of
      release profile in manifestation of different therapeutic outcomes. Thus, this
      work endows niclosamide a new life for anticancer application which has remained
      elusive till date due to its hydrophobic nature. 

PMID- 25988282
TI  - Modification of oral absorption of oxyresveratrol using lipid based
      nanoparticles.
AB  - The aim of this study was to develop and assess nanostructured lipid carriers
      (NLC) compared to solid lipid nanoparticles (SLN) for improving the oral
      bioavailability of oxyresveratrol (OXY). The OXY formulated as SLN (OXY-SLN) and
      NLC (OXY-NLC) were prepared by a high shear homogenization technique. The
      optimized OXY-NLC (NLC3) produced smaller nanoparticle sizes (96+/-0.9nm) than
      that of the OXY-SLN (108+/-0.3nm) with a homogeneous size distribution and a high
      zeta potential. The spherical NLC had a significantly higher efficiency for OXY
      entrapment (89+/-0.1%) and a better stability than the SLN after storage for 12
      months at 4+/-2 degrees C according to parameters such as smaller particles,
      greater zeta potential and a higher loading capacity (p<0.05). Differential
      scanning calorimetry (DSC) showed a less ordered crystalline structure of NLC
      than SLN. The accumulated drug in an amorphous state in the NLC was also
      confirmed by powder X-ray diffraction (PXRD). The in vitro release profiles of
      the OXY-NLC showed a more sustained release compared to the SLN and unformulated
      OXY. The in vivo pharmacokinetic profiles implied enterohepatic recycling of OXY
      in the Wistar rat. Meanwhile, the oral absorption pattern of OXY was modified by
      both types of lipid nanoparticles. The SLN and NLC increased the relative
      bioavailability of OXY to 125% and 177%, respectively, compared with unformulated
      OXY. These findings indicated that NLC could be used as a potential carrier to
      improve the oral bioavailability of OXY. 

PMID- 25988283
TI  - Polymeric complex micelles with double drug-loading strategies for folate
      mediated paclitaxel delivery.
AB  - Drug loading is a key procedure in the preparation of drug-loaded nano-carriers.
      In this study, the paclitaxel (PTX)-loaded polymeric complex micelles (FA-P123
      PTX/PTX micelles) with double drug-loading strategies were designed and prepared
      to improve the drug loading percentage of carriers and its anti-tumor efficiency.
      PTX was simultaneously conjugated to pluronic P123 (P123) polymer and
      encapsulated inside the P123 complex micelle. Folate (FA) was linked to the
      surface of micelles for the active target delivery of micelles to tumor cells.
      The FA-P123-PTX/PTX micelles showed spherical shaped with high drug loading of
      18.08+/-0.64%. The results of cellular uptake studies suggested that FA could
      promote the internalization of micelles into the FR positive cells. FA-P123
      PTX/PTX micelles showed significant higher anti-tumor activity against FR
      positive tumor cells compared to Taxol((r)) (p<0.05). Moreover, the FA-P123
      PTX/PTX micelles exhibited higher anti-tumor efficacy in B16 bearing mice with
      better safety property compared with Taxol((r)). These results suggested that FA
      P123-PTX/PTX micelles with double drug-loading strategies showed great potential
      for targeted delivery of anti-cancer drugs. 

PMID- 25988284
TI  - Wilson's disease with cognitive impairment and without extrapyramidal signs:
      improvement of neuropsychological performance and reduction of MRI abnormalities
      with trientine treatment.
AB  - Extrapyramidal signs are neurological dysfunction commonly associated with
      Wilson's disease (WD). In addition, cognitive dysfunction has been reported in
      the early stages of WD. In this report, we describe a 49-year-old woman
      presenting with memory impairments and without Parkinsonian or extrapyramidal
      signs. She was diagnosed with WD based on the presence of Kayser-Fleischer rings
      around the irises of her eyes and two ATP7B gene mutations, R778L at exon 8 and
      A874V at exdyon 11. Serial magnetic resonance imaging analysis and
      neuropsychological tests showed improvements following treatment with trientine. 

PMID- 25988285
TI  - When blood transfusion medicine becomes complicated due to interference by
      monoclonal antibody therapy.
AB  - BACKGROUND: Monoclonal antibodies (MoAbs) are increasingly integrated in the
      standard of care. The notion that therapeutic MoAbs can interfere with clinical
      laboratory tests is an emerging concern that requires immediate recognition and
      the development of appropriate solutions. Here, we describe that treatment of
      multiple myeloma patients with daratumumab, a novel anti-CD38 MoAb, resulted in
      false-positive indirect antiglobulin tests (IATs) for all patients for 2 to 6
      months after infusion. This precluded the correct identification of irregular
      blood group antibodies for patients requiring blood transfusion. STUDY DESIGN AND
      METHODS: The IAT was performed using three- and 11-donor-cell panels.
      Interference of daratumumab and three other anti-CD38 MoAbs was studied using
      fresh-frozen plasma spiked with different MoAb concentrations. Additionally it
      was tested whether two potentially neutralizing agents, anti-idiotype antibody
      and recombinant soluble CD38 (sCD38) extracellular domain, were able to inhibit
      the interference. RESULTS: The CD38 MoAbs caused agglutination in the IAT in a
      dose-dependent manner. Addition of an excess of anti-idiotype antibodies or sCD38
      protein to the test abrogated CD38 MoAb interference and successfully restored
      irregular antibody screening and identification. DISCUSSION: CD38 MoAb therapy
      causes false-positive results in the IAT. The reliability of the test could be
      restored by adding a neutralizing agent against the CD38 MoAb to the patient's
      plasma. This study emphasizes that during drug development, targeted therapeutics
      should be investigated for potential interference with laboratory tests. Clinical
      laboratories should be informed when patients receive MoAb treatments and matched
      laboratory tests to prevent interference should be employed.

PMID- 25988286
TI  - Flash Flood Risks and Warning Decisions: A Mental Models Study of Forecasters,
      Public Officials, and Media Broadcasters in Boulder, Colorado.
AB  - Timely warning communication and decision making are critical for reducing harm
      from flash flooding. To help understand and improve extreme weather risk
      communication and management, this study uses a mental models research approach
      to investigate the flash flood warning system and its risk decision context. Data
      were collected in the Boulder, Colorado area from mental models interviews with
      forecasters, public officials, and media broadcasters, who each make important
      interacting decisions in the warning system, and from a group modeling session
      with forecasters. Analysis of the data informed development of a decision-focused
      model of the flash flood warning system that integrates the professionals'
      perspectives. Comparative analysis of individual and group data with this model
      characterizes how these professionals conceptualize flash flood risks and
      associated uncertainty; create and disseminate flash flood warning information;
      and perceive how warning information is (and should be) used in their own and
      others' decisions. The analysis indicates that warning system functioning would
      benefit from professionals developing a clearer, shared understanding of flash
      flood risks and the warning system, across their areas of expertise and job
      roles. Given the challenges in risk communication and decision making for
      complex, rapidly evolving hazards such as flash floods, another priority is
      development of improved warning content to help members of the public protect
      themselves when needed. Also important is professional communication with members
      of the public about allocation of responsibilities for managing flash flood
      risks, as well as improved system-wide management of uncertainty in decisions. 

PMID- 25988288
TI  - The Arteries of the Brain in Hare (Lepus europaeus Pallas, 1778).
AB  - Research into course and variability of brain arteries in hare were performed on
      38 adult hares of both sexes (males 23 and females 15). The arteries were filled
      with a synthetic latex at a constant pressure introduced with a medical syringe
      to the left ventricle. The source of blood supply to the brain was internal
      carotid arteries, whose branches formed an arterial circle of the brain,
      vertebral arteries, and basilar artery as the result of its anastomosis.
      Variability focused on a method of departure of middle cerebral arteries, which
      were multiple vessels in 39.5% of cases and rostral cerebellar arteries. Caudal
      communicating arteries in hare comprised bilateral anastomosis of internal
      carotid arteries and final branches of the basilar artery. It stabilized the
      steady flow of blood to all parts of the brain. Caudal cerebral arteries
      comprised final branches of the basilar artery. The largest capacity of all the
      arteries of the brain was observed in the main trunk of the basilar artery. The
      capacity of these vessels was 4.53 mm(3) on average. The factor of capacity of
      cerebral arteries in relation to weight of the brain reaches a high value in
      hare.

PMID- 25988289
TI  - Stress and Premenstrual Symptoms in Reproductive-Aged Women.
AB  - Premenstrual symptoms are often reported from reproductive-aged women worldwide.
      The etiologies of the symptoms are complex (e.g., biological and sociocultural
      factors), and require an international and multidisciplinary approach. A total of
      48 studies were reviewed on how stress and premenstrual symptoms have been
      defined and measured, and major findings on relational patterns and other
      associated factors were examined. Subsequently, we discuss several trends and
      limitations identified from the review. Prospective studies, which use valid
      assessment measures and consider women's subjective and objective symptoms for
      several menstrual cycles, are necessary for a valid conclusion. More intervention
      studies and studies on various populations are needed. 

PMID- 25988287
TI  - Improved dissolution and absorption of ketoconazole in the presence of organic
      acids as pH-modifiers.
AB  - Formulation development of poorly water-soluble compounds can be challenging
      because of incomplete dissolution that causes low and variable bioavailability.
      Enhancing compound solubility is important and many techniques have been
      investigated to that end, but they require specific materials and machinery. This
      study investigates the incorporation of a pH-modifier as a method to increase
      compound solubility and uses ketoconazole (KZ), which is weakly basic (pKa: 6.5),
      as a model compound. Organic acids are effective pH-modifiers and are generally
      used in pharmaceutical industries. We successfully obtained granules containing
      variable organic acids (KZ/acid granule) using a high-shear mixer. Dissolution
      tests of the KZ/acid granule resulted in highly enhanced solubility under non
      sink conditions. Adding water-soluble acids, such as citric acid (CA) and
      tartaric acid, resulted in more than 8-fold higher dissolution at pH 6.0 compared
      to that of KZ only. The granules containing citric acid (KZ/CA granule) improved
      the dissolution of KZ after oral administration to rats under low gastric acid
      conditions, where the bioavailability of the KZ/CA granules at elevated gastric
      pH was comparable with that of KZ only at gastric acidic pH. The incorporation of
      organic acids would result in effective therapeutic outcomes independent of
      gastric pH in patients. In addition, higher bioavailability of KZ was observed
      after oral administration of KZ/CA granules under gastric acidic pH conditions
      than that of KZ alone. Thus, CA improved the dissolution and absorption rate of
      KZ after oral administration. 

PMID- 25988291
TI  - Preoperative chemotherapy for resectable thoracic esophageal cancer.
AB  - BACKGROUND: Surgery has been the treatment of choice for patients with localized
      esophageal cancer. Several studies have investigated whether preoperative
      chemotherapy followed by surgery leads to improvement in cure rates, but
      individual reports have provided conflicting results. An explicit systematic
      update of the role of preoperative chemotherapy in the treatment of patients with
      resectable thoracic esophageal cancer is, therefore, warranted. OBJECTIVES: The
      objective of this review is to determine the role of preoperative chemotherapy in
      the treatment of patients with resectable thoracic esophageal carcinoma. SEARCH
      METHODS: We identified trials by searching the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE (1966 to 2013), EMBASE (1988 to 2013), and
      CANCERLIT (1993 to 2013). We did not confine our search to English language
      publications. We updated searches in CENTRAL, MEDLINE, and EMBASE in October
      2013. SELECTION CRITERIA: All trials of patients with potentially resectable
      carcinoma of the esophagus (of any histologic type) who were randomly assigned to
      chemotherapy or no chemotherapy before surgery. DATA COLLECTION AND ANALYSIS: The
      primary outcome was survival, which was assessed with the use of hazard ratios.
      This is an amendment to the original review, which used risk ratios to assess
      survival at yearly intervals. Hazard ratios (HRs) have now been introduced to
      summarize the complete survival experience in a single analysis. Risk ratios
      (RRs) were used to compare rates of resection, tumor recurrences, and treatment
      morbidity and mortality. MAIN RESULTS: We identified a total of 13 randomized
      trials involving 2362 participants. Ten trials (2122 participants) reported
      sufficient detail on survival to be included in a meta-analysis for the primary
      outcome. Preoperative chemotherapy improves overall survival (HR 0.88, 95%
      confidence interval (CI) 0.80 to 0.96) and is associated with a significantly
      higher rate of complete (R0) resection (RR 1.11, 95% CI 1.03 to 1.19).No evidence
      suggests that the overall rate of resection (RR 0.96, 95% CI 0.92 to 1.01), tumor
      recurrence (RR 0.81, 95% CI 0.54 to 1.22) or nonfatal complications (RR 0.90; 95%
      CI 0.76 to 1.06) was different for preoperative chemotherapy compared with
      surgery alone. Trials reported risks of toxicity with chemotherapy that ranged
      from 11% to 90%. AUTHORS' CONCLUSIONS: In summary, preoperative chemotherapy plus
      surgery offers a survival advantage compared with surgery alone for patients with
      resectable thoracic esophageal cancer, but the evidence is of moderate quality.
      Some evidence of toxicity and preoperative mortality have been associated with
      chemotherapy.

PMID- 25988292
TI  - microRNA miR-10b inhibition reduces cell proliferation and promotes apoptosis in
      non-small cell lung cancer (NSCLC) cells.
AB  - Lung cancer is one of the most common and serious types of cancer. Till now, the
      treatment of lung cancer has been unsatisfactory, which is associated with poor
      prognosis and high mortality. Therefore, there is an urgent requirement to
      investigate the molecular mechanisms underlying lung tumorigenesis. To study the
      potential function of miR-10b involved in the regulation of lung tumors, we
      monitored NSCLC cell behaviour including proliferation, apoptosis and cell cycle
      using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the
      expression levels of miR-10b in 75 NSCLC patients' tissues and Western blot was
      also used to analyze the expression level of genes correlated with apoptosis in
      NSCLC cells. miR-10b expression levels were higher in NSCLC tissues compared with
      an adjacent normal tissue control. Silencing of miR-10b inhibited cancer cell
      progress by arresting cell cycle progression in the G0/G1 phase and promoted
      apoptosis in NSCLC cells. Western blot analysis of miR-10b-silenced cells
      revealed up-regulation of apoptosis-inducing members Fas, FasL, Bax and caspase
      3, and down-regulation of apoptosis-inhibiting factors Bcl-2 and PCNA. And, a
      significant inverse correlation between the level of miR-10b and klotho was
      observed, which has been demonstrated to be a novel tumor suppressor gene. A
      further in vivo tumor formation study in nude mice indicated that inhibition of
      miR-10b in lung cancer cells delayed the progress of tumor formation. These
      findings indicated that miR-10b might serve as a useful potential target for
      treatment of NSCLC. 

PMID- 25988290
TI  - Human CD45RA(-) FoxP3(hi) Memory-Type Regulatory T Cells Show Distinct TCR
      Repertoires With Conventional T Cells and Play an Important Role in Controlling
      Early Immune Activation.
AB  - Adoptive immunotherapy with regulatory T cells (Treg) is a new option to promote
      immune tolerance following solid organ transplantation (SOT). However, Treg from
      elderly patients awaiting transplantation are dominated by the CD45RA(-) CD62L(+)
      central memory type Treg subset (TregCM), and the yield of well-characterized and
      stable naive Treg (TregN) is low. It is, therefore, important to determine
      whether these TregCM are derived from the thymus and express high stability,
      suppressive capacity and a broad antigen repertoire like TregN. In this study, we
      showed that TregCM use a different T cell receptor (TCR) repertoire from
      conventional T cells (Tconv), using next-generation sequencing of all 24 Vbeta
      families, with an average depth of 534 677 sequences. This showed almost no
      contamination with induced Treg. Furthermore, TregCM showed enhanced suppressive
      activity on Tconv at early checkpoints of immune activation controlling
      activation markers expression and cytokine secretion, but comparable inhibition
      of proliferation. Following in vitro expansion under mTOR inhibition, TregCM
      expanded equally as well as TregN without losing their function. Despite
      relatively limited TCR repertoire, TregCM also showed specific alloresponse,
      although slightly reduced compared to TregN. These results support the
      therapeutic usefulness of manufacturing Treg products from CD45RA(-) CD62L(+)
      Treg-enriched starting material to be applied for adoptive Treg therapy. 

PMID- 25988294
TI  - Reactivity and Catalytic Activity of Hydrogen Atom Chemisorbed Silver Clusters.
AB  - Metal clusters of silver have attracted recent interest of researchers as a
      result of their potential in different catalytic applications and low cost.
      However, due to the completely filled d orbital and very high first ionization
      potential of the silver atom, the silver-based catalysts interact very weakly
      with the reacting molecules. In the current work, density functional theory
      calculations were carried out to investigate the effect of hydrogen atom
      chemisorption on the reactivity and catalytic properties of inert silver
      clusters. Our results affirm that the hydrogen atom chemisorption leads to
      enhancement in the binding energy of the adsorbed O2 molecule on the inert silver
      clusters. The increase in the binding energy is also characterized by the
      decrease in the Ag-O and increase in the O-O bond lengths in the case of the AgnH
      silver clusters. Pertinent to the increase in the O-O bond length, a significant
      red shift in the O-O stretching frequency is also noted in the case of the AgnH
      silver clusters. Moreover, the hydrogen atom chemisorbed silver clusters show low
      reaction barriers and high heat of formation of the final products for the
      environmentally important CO oxidation reaction as compared to the parent
      catalytically inactive clusters. The obtained results were compared with those of
      the corresponding gold and hydrogen atom chemisorbed gold clusters obtained at
      the same level of theory. It is expected the current computational study will
      provide key insights for future advances in the design of efficient nanosilver
      based catalysts through the adsorption of a small atom or a ligand. 

PMID- 25988293
TI  - Prediction of small-for-gestational-age neonates: screening by biophysical and
      biochemical markers at 19-24 weeks.
AB  - OBJECTIVE: To investigate the value of combined screening by maternal
      characteristics and medical history, fetal biometry and biophysical and
      biochemical markers at 19-24 weeks' gestation, for prediction of delivery of
      small-for-gestational-age (SGA) neonates, in the absence of pre-eclampsia (PE),
      and examine the potential value of such assessment in deciding whether the third
      trimester scan should be at 32 and/or 36 weeks' gestation. METHODS: This was a
      screening study in 7816 singleton pregnancies, including 389 (5.0%) that
      delivered SGA neonates with birth weight < 5(th) percentile (SGA < 5(th) ), in
      the absence of PE. Multivariable logistic regression analysis was used to
      determine if screening by a combination of maternal factors, fetal biometry,
      uterine artery pulsatility index (UtA-PI) and maternal serum concentrations of
      placental growth factor (PlGF) and alpha-fetoprotein (AFP) had significant
      contribution in predicting SGA neonates. A model was developed for selecting the
      gestational age for third-trimester assessment, at 32 and/or 36 weeks, based on
      the results of screening at 19-24 weeks. RESULTS: Significant independent
      contributions to the prediction of SGA < 5(th) were provided by maternal factors,
      fetal biometry, UtA-PI and serum PlGF and AFP. The detection rate (DR) of such
      combined screening at 19-24 weeks was 100%, 78% and 42% for SGA < 5(th)
      delivering < 32, at 32-36 and >= 37 weeks' gestation, respectively, at a false
      positive rate (FPR) of 10%. In a hypothetical model, it was estimated that if the
      desired objective of prenatal screening is to predict about 80% of the cases of
      SGA < 5(th) , it would be necessary to select 11% of the population at the 19-24
      week assessment to be reassessed at 32 weeks and 44% to be reassessed at 36
      weeks; 57% would not require a third-trimester scan. CONCLUSION: Prenatal
      prediction of a high proportion of SGA neonates necessitates the undertaking of
      screening in the third trimester of pregnancy, in addition to assessment in the
      second trimester, and the timing of such screening, at 32 and/or 36 weeks, should
      be contingent on the results of the assessment at 19-24 weeks.

PMID- 25988295
TI  - Stability of the Liquid State of Imidazolium-Based Ionic Liquids under High
      Pressure at Room Temperature.
AB  - To understand the stability of the liquid phase of ionic liquids under high
      pressure, we investigated the phase behavior of a series of 1-alkyl-3
      methylimidazolium tetrafluoroborate ([Cnmim][BF4]) homologues with different
      alkyl chain lengths for 2 <= n <= 8 up to ~7 GPa at room temperature. The ionic
      liquids exhibited complicated phase behavior, which was likely due to the
      conformational flexibility in the alkyl chain. The present results reveal that
      [Cnmim][BF4] falls into superpressed state around 2-3 GPa range upon compression
      with an implication of multiple phase or structural transitions to ~7 GPa.
      Remarkably, a characteristic nanostructural organization in ionic liquids largely
      diminishes at the superpressed state. The behaviors of imidazolium-based ionic
      liquids can be classified into, at least, three patterns: (1) pressure-induced
      crystallization, (2) superpressurization upon compression, and (3) decompression
      induced crystallization from the superpressurized glass. Interestingly, the high
      pressure phase behavior was relevant to the glass transition behavior at low
      temperatures and ambient pressure. As n increases, the glass transition pressure
      (pg) decreases (from 2.8 GPa to ~2 GPa), and the glass transition temperature
      increases. The results indicate that the p-T range of the liquid phase is
      regulated by the alkyl chain length of [Cnmim][BF4] homologues. 

PMID- 25988296
TI  - Human serum albumin-mimetic chromatography based hexadecyltrimethylammonium
      bromide as a novel direct probe for protein binding of acidic drugs.
AB  - Human serum albumin (HSA) is the most important drug carrier in humans mainly
      binding acidic drugs. Negatively charged compounds bind more strongly to HSA than
      it would be expected from their lipophilicity alone. With the development of new
      acidic drugs, there is a high need for rapid and simple protein binding screening
      technologies. Biopartitioning micellar chromatography (BMC) is a mode of micellar
      liquid chromatography, which can be used as an in vitro system to model the
      biopartitioning process of drugs when there are no active processes. In this
      study, a new kind of BMC using hexadecyltrimethylammonium bromide (CTAB) as
      micellar mobile phases was used for the prediction of protein binding of acidic
      drugs based on the similar property of CTAB micelles to HSA. The use of BMC is
      simple, reproducible and can provide key information about the pharmacological
      behavior of drugs such as protein binding properties of new compounds during the
      drug discovery process. The relationships between the MLC retention data of a
      heterogeneous set of 17 acidic and neutral drugs and their plasma protein binding
      parameter were studied and second-order polynomial models obtained in two
      different concentrations (0.07 and 0.09M) of CTAB. However, the developed models
      are only being able to distinguish between strongly and weakly binding drugs.
      Also, the developed models were characterized by both the descriptive and
      predictive ability (R(2)=0.885, RCV(2)=0.838 and R(2)=0.898, RCV(2)=0.859 for
      0.07 and 0.09M CTAB, respectively). The application of the developed model to a
      prediction set demonstrated that the model was also reliable with good predictive
      accuracy. 

PMID- 25988297
TI  - Validation of a confirmatory method of salbutamol in sheep hair by UPLC-MS/MS and
      its application to pharmacokinetic study.
AB  - A new method for determining salbutamol in hair of sheep by ultra-performance
      liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was established.
      Samples were extracted with 0.1M of HCl solution. The mixture was heated to 60 
      degrees C in a water bath and kept at this temperature for 4h. The extracts were
      purified through SPE method and then dried with nitrogen. Residues were
      redissolved in mobile phase. The target compound was determined by UPLC-MS/MS
      with BEH-C18 column. The usefulness and feasibility of different treatment
      procedures of hair containing salbutamol were evaluated. The range of linearity
      was 1-100 ng/g. The LOD was 0.3 ng/g, and the LOQ was 1 ng/g. Recoveries were 89
      106%, and coefficients of variation were 3.2-13.9%. Pharmacokinetics of
      salbutamol was studied in healthy sheep after oral administration of 150 MUg/kg
      body weight salbutamol for 21 consecutive days. Salbutamol residues in hair were
      still detected after 21 days of administration.

PMID- 25988298
TI  - Albumin infusion in cirrhotic patients with infections other than spontaneous
      bacterial peritonitis: End of the story?

PMID- 25988299
TI  - Additional drug resistance of multidrug-resistant tuberculosis in patients in 9
      countries.
AB  - Data from a large multicenter observational study of patients with multidrug
      resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2
      new approaches to treatment of MDR TB: a short (9-month) regimen and a
      bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance
      to fluoroquinolones and second-line injectable drugs and thus would qualify as
      candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a
      fluoroquinolone or second-line injectable drug would qualify as candidates for a
      bedaquiline-containing regimen in accordance with published guidelines. Among
      candidates for the 9-month regimen, standardized drug-susceptibility tests
      demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs.
      Among candidates for bedaquiline, drug-susceptibility tests demonstrated
      susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained
      susceptibility to <2 drugs. These data may assist national TB programs in
      planning to implement new drugs and drug regimens. 

PMID- 25988300
TI  - Evidence for nodeless superconductivity in NdO(1-x)F(x)BiS2 (x = 0.3 and 0.5)
      single crystals.
AB  - We study the superconducting pairing states of NdO(1-x)F(x)BiS2 (x = 0.3 and 0.5)
      by measuring the magnetic penetration depth Deltalambda(T) using the tunnel-diode
      oscillator (TDO) technique. An upturn is observed in Deltalambda(T) as well as
      the magnetic susceptibility chi(T) in the low-temperature limit, which is
      attributed to the paramagnetism of Nd ions. After subtracting the paramagnetic
      contributions, the penetration depth Deltalambda(T) follows an exponential-type
      temperature dependence at T ? T(c), providing evidence of nodeless
      superconductivity for NdO(1-x)F(x)BiS2. This is further supported by the analyses
      of superfluid density rho(s)(T), which can be well described by a BCS model with
      an energy gap of Delta(0) ~ 2.15 k(B)T(c).

PMID- 25988301
TI  - Endemic melioidosis in residents of desert region after atypically intense
      rainfall in central Australia, 2011.
AB  - After heavy rains and flooding during early 2011 in the normally arid interior of
      Australia, melioidosis was diagnosed in 6 persons over a 4-month period. Although
      the precise global distribution of the causal bacterium Burkholderia pseudomallei
      remains to be determined, this organism can clearly survive in harsh and even
      desert environments outside the wet tropics. 

PMID- 25988302
TI  - Dermoscopic features in 12 cats with dermatophytosis and in 12 cats with self
      induced alopecia due to other causes: an observational descriptive study.
AB  - BACKGROUND: Dermoscopy is a noninvasive technique allowing rapid magnified in
      vivo observation of the skin and structures that lie beneath the skin surface.
      Various congenital and acquired hair shaft abnormalities may also be evaluated by
      dermoscopy. Additionally, characteristic features of Microsporum canis-induced
      tinea capitis and trichotillomania in humans have been reported. OBJECTIVES: To
      describe the dermoscopic findings observed in cats with patchy alopecia due to M.
      canis infection and in cats with self-inflicted hair loss. ANIMALS: Twenty-four
      client-owned cats presented at a veterinary referral practice. METHODS:
      Dermoscopy was performed with a hand-held nonpolarized light dermoscope at 10
      fold magnification. The glass plate of the dermoscope was applied gently to the
      lesions and no sedation was required. RESULTS: Twelve cats were diagnosed with
      dermatophytosis and 12 with self-induced alopecia due to other causes. At 10-fold
      magnification, the most characteristic findings observed in circumscribed lesions
      of cats with dermatophytosis were opaque, slightly curved, broken hairs of a
      homogeneous thickness (comma-like structures) and a variable amount of brown-to
      yellow greasy scales. In cats with self-induced alopecia, multiple hairs with a
      normal shaft cleanly broken at different lengths, short tufts of hairs broken at
      an equal level and hook-like and coiled hairs were observed. CONCLUSIONS AND
      CLINICAL IMPORTANCE: This observational descriptive study suggests that
      dermoscopy may represent a helpful noninvasive in vivo technique in the
      differential diagnosis of patchy alopecia in cats.

PMID- 25988303
TI  - Factors predicting 30-day readmission after laparoscopic colorectal cancer
      surgery within an enhanced recovery programme.
AB  - AIM: Hospital readmission within 30 days of surgery has become a marker of poor
      quality patient care. This study aimed to investigate factors predictive of 30
      day readmission after laparoscopic colorectal cancer surgery within an enhanced
      recovery after surgery (ERAS) programme. METHOD: Consecutive patients undergoing
      laparoscopic surgery for colorectal cancer within an ERAS programme between 2002
      and 2009 were included. Data were collected relating to patient demographics,
      neoadjuvant chemoradiotherapy, ERAS compliance, and operative and postoperative
      outcomes. A logistic regression model was used to identify factors associated
      with readmissions after adjusting for the potential effect of covariables
      simultaneously. RESULTS: In all, 268 cancer patients underwent laparoscopic
      colorectal surgery (108 rectal resections), of whom 34 (12.7%) were readmitted
      due most commonly to bowel obstruction (29%) and surgical site infection (18%).
      The use of neoadjuvant therapy (odds ratio 4.49, 95% CI 1.41-14.35; P = 0.011)
      and ERAS compliance above 93% (odds ratio 0.38, 95% CI 0.18-0.84; P = 0.016) were
      independent predictors of readmission. CONCLUSION: Poor ERAS compliance and
      preoperative chemoradiotherapy were significant predictors of readmission
      following laparoscopic colorectal cancer surgery. Further research is required to
      expand the scope of ERAS beyond hospital discharge.

PMID- 25988304
TI  - Integrating small molecule signalling and H-NS antagonism in Vibrio cholerae, a
      bacterium with two chromosomes.
AB  - H-NS is a well-established silencer of virulence gene transcription in the human
      pathogen Vibrio cholerae. Biofilm formation aids V. cholerae in colonizing both
      its host and its external environments, and H-NS silences biofilm gene
      expression. Cyclic-di-guanosine monophosphate acts through the DNA binding
      proteins VpsR and VpsT to overcome H-NS-mediated repression of biofilm genes,
      driving a transition between a planktonic and a colonial/biofilm lifestyle. The H
      NS binding pattern has now been charted on both chromosomes in V. cholerae, but
      whether or not this abundant DNA-binding-and-bridging protein plays any roles in
      nucleoid organization in this bacterium remains an open question. 

PMID- 25988305
TI  - The many meanings of gross photosynthesis and their implication for
      photosynthesis research from leaf to globe.

PMID- 25988306
TI  - Expanded Porphyrins as Two-Dimensional Porous Membranes for CO2 Separation.
AB  - Porphyrin-based two-dimensional polymers have uniform micropores and close to
      atom-thin thicknesses, but they have not been explored for gas separation. Herein
      we design various expanded porphyrin derivatives for their potential application
      in membrane gas separation, using CO2/N2 as an example. Pore sizes are determined
      based on both van der Waals radii and electron density distribution. Potential
      energy curves for CO2 and N2 passing through are mapped by dispersion-corrected
      density functional theory calculations. The passing-through barriers are used to
      evaluate CO2/N2 separation selectivity. Promising subunits for CO2 separation
      have been selected from the selectivity estimates. 2D membranes composed of
      amethyrin derivatives are shown to have high ideal selectivity on the order of
      10(6) for CO2/N2 separation. Classical molecular dynamics simulation yields a
      permeance of 10(4)-10(5) GPU for CO2 through extended 2D membranes based on
      amethyrin derivatives. This work demonstrates that porphyrin systems could offer
      an attractive bottom-up approach for 2D porous membranes. 

PMID- 25988307
TI  - Autophagy--a fundamental cellular mechanism on the verge of clinical translation.

PMID- 25988308
TI  - Reduced forced vital capacity in Aboriginal Australians: Biology or missing
      evidence?

PMID- 25988309
TI  - Micropollutant removal from wastewater: facts and decision-making despite
      uncertainty.

PMID- 25988310
TI  - Impulsivity and reasons for living among African American youth: a risk
      protection framework of suicidal ideation.
AB  - This study aims to explore the impact of specific facets of impulsivity as
      measured by the UPPS Impulsive Behavior Scale (UPPS), as well as reasons for
      living in predicting suicidal ideation among African American college-aged
      students. The incremental validity of each facet of the UPPS interacting with
      reasons for living, a construct meant to buffer against risk for suicide, was
      explored in a sample of African American students (N = 130; ages 18-24). Results
      revealed significant interactions between reasons for living and two factors of
      impulsivity, (lack of) premeditation and sensation seeking. Higher levels of
      sensation seeking and lack of premeditation in conjunction with lower reasons for
      living was associated with increased suicidal ideation. Neither urgency nor (lack
      of) perseverance significantly interacted with reasons for living in association
      with suicidal ideation. These results suggest including elements of impulsivity,
      specifically sensation seeking and (lack of) premeditation, when screening for
      suicidal ideation among African American youth. Future investigations should
      continue to integrate factors of both risk and protection when determining risk
      for suicide. 

PMID- 25988311
TI  - Are metals emitted from electronic cigarettes a reason for health concern? A risk
      assessment analysis of currently available literature.
AB  - BACKGROUND: Studies have found that metals are emitted to the electronic
      cigarette (EC) aerosol. However, the potential health impact of exposure to such
      metals has not been adequately defined. The purpose of this study was to perform
      a risk assessment analysis, evaluating the exposure of electronic cigarette (EC)
      users to metal emissions based on findings from the published literature.
      METHODS: Two studies were found in the literature, measuring metals emitted to
      the aerosol from 13 EC products. We estimated that users take on average 600 EC
      puffs per day, but we evaluated the daily exposure from 1200 puffs. Estimates of
      exposure were compared with the chronic Permissible Daily Exposure (PDE) from
      inhalational medications defined by the U.S. Pharmacopeia (cadmium, chromium,
      copper, lead and nickel), the Minimal Risk Level (MRL) defined by the Agency for
      Toxic Substances and Disease Registry (manganese) and the Recommended Exposure
      Limit (REL) defined by the National Institute of Occupational Safety and Health
      (aluminum, barium, iron, tin, titanium, zinc and zirconium). RESULTS: The average
      daily exposure from 13 EC products was 2.6 to 387 times lower than the safety cut
      off point of PDEs, 325 times lower than the safety limit of MRL and 665 to 77,514
      times lower than the safety cut-off point of RELs. Only one of the 13 products
      was found to result in exposure 10% higher than PDE for one metal (cadmium) at
      the extreme daily use of 1200 puffs. Significant differences in emissions between
      products were observed. CONCLUSIONS: Based on currently available data, overall
      exposure to metals from EC use is not expected to be of significant health
      concern for smokers switching to EC use, but is an unnecessary source of exposure
      for never-smokers. Metal analysis should be expanded to more products and
      exposure can be further reduced through improvements in product quality and
      appropriate choice of materials.

PMID- 25988313
TI  - DNA barcoding and morphological identification of neotropical ichthyoplankton
      from the Upper Parana and Sao Francisco.
AB  - The identification of fish larvae from two neotropical hydrographic basins using
      traditional morphological taxonomy and DNA barcoding revealed no conflicting
      results between the morphological and barcode identification of larvae. A lower
      rate (25%) of correct morphological identification of eggs as belonging to
      migratory or non-migratory species was achieved. Accurate identification of
      ichthyoplankton by DNA barcoding is an important tool for fish reproductive
      behaviour studies, correct estimation of biodiversity by detecting eggs from rare
      species, as well as defining environmental and management strategies for fish
      conservation in the neotropics. 

PMID- 25988312
TI  - Prevalence of Marijuana Use among University Students in Bolivia, Colombia,
      Ecuador, and Peru.
AB  - Young adults 18 to 25 years old show the highest prevalence of marijuana use in
      Latin America. This study analyzes the changes in prevalence of marijuana use
      among university students in the Andean Community (Bolivia, Colombia, Ecuador,
      and Peru) from two studies carried out in 2009 and in 2012. Data were collected
      through representative two-stage samples of universities and students in the
      Andean Community. An online survey was administered using a standardized
      questionnaire. Prevalence was calculated for lifetime, past year, and past month.
      Marijuana was the most widely used illicit substance consumed among university
      students, in 2009 and in 2012. Past month prevalence among university students in
      2009 in Colombia was 5.27%, in Peru 1.00%, in Ecuador 1.68%, and in Bolivia
      0.76%. Past month prevalence in 2012 in Colombia was 7.14%, in Ecuador 3.67%, in
      Peru 1.62%, and in Bolivia 1.45% in 2012. Among university students in the Andean
      Community, past month prevalence increased among both males and females between
      2009 and 2012 in most countries. Marijuana continues to be the most commonly used
      illicit drug in Latin American countries. Increases in prevalence among young
      adults could have important implications for national drug policy. 

PMID- 25988314
TI  - Case of Hermansky-Pudlak syndrome 1 in a Japanese infant.

PMID- 25988315
TI  - ImmuSort, a database on gene plasticity and electronic sorting for immune cells.
AB  - Gene expression is highly dynamic and plastic. We present a new immunological
      database, ImmuSort. Unlike other gene expression databases, ImmuSort provides a
      convenient way to view global differential gene expression data across thousands
      of experimental conditions in immune cells. It enables electronic sorting, which
      is a bioinformatics process to retrieve cell states associated with specific
      experimental conditions that are mainly based on gene expression intensity. A
      comparison of gene expression profiles reveals other applications, such as the
      evaluation of immune cell biomarkers and cell subsets, identification of cell
      specific and/or disease-associated genes or transcripts, comparison of gene
      expression in different transcript variants and probe set quality evaluation. A
      plasticity score is introduced to measure gene plasticity. Average rank and
      marker evaluation scores are used to evaluate biomarkers. The current version
      includes 31 human and 17 mouse immune cell groups, comprising 10,422 and 3,929
      microarrays derived from public databases, respectively. A total of 20,283 human
      and 20,963 mouse genes are available to query in the database. Examples show the
      distinct advantages of the database. The database URL is
      http://202.85.212.211/Account/ImmuSort.html. 

PMID- 25988316
TI  - Robo1/2 regulate follicle atresia through manipulating granulosa cell apoptosis
      in mice.
AB  - Secreted Slit proteins and their Roundabout (Robo) receptors act as a repulsive
      cue to prevent axons from migrating to inappropriate locations during the
      development of the nervous system. Slit/Robo has also been implicated in
      reproductive system development, but the molecular mechanism of the Slit/Robo
      pathway in the reproductive system remains poorly understood. Using a transgenic
      mouse model, we investigated the function of the Slit/Robo pathway on ovarian
      follicle development and atresia. We first demonstrated that more offspring were
      born to mice with a partial knockout of the Robo1/2 genes in mice. We next showed
      that Robo1 and Robo2 are strongly expressed in ovarian granulosa cells. Apoptosis
      in granulosa cells was reduced when Robo1/2 were partially knocked out, and this
      observation was further verified by in vitro Robo1/2 knockout experiments in
      mouse and human granulosa cells. We also found that ovarian angiogenesis was
      enhanced by a partial lack of Robo1/2 genes. In summary, our data suggest that
      the Slit/Robo pathway can impact follicle development and atresia by influencing
      granulosa cell apoptosis.

PMID- 25988318
TI  - Digital Ecology: Coexistence and Domination among Interacting Networks.
AB  - The overwhelming success of Web 2.0, within which online social networks are key
      actors, has induced a paradigm shift in the nature of human interactions. The
      user-driven character of Web 2.0 services has allowed researchers to quantify
      large-scale social patterns for the first time. However, the mechanisms that
      determine the fate of networks at the system level are still poorly understood.
      For instance, the simultaneous existence of multiple digital services naturally
      raises questions concerning which conditions these services can coexist under.
      Analogously to the case of population dynamics, the digital world forms a complex
      ecosystem of interacting networks. The fitness of each network depends on its
      capacity to attract and maintain users' attention, which constitutes a limited
      resource. In this paper, we introduce an ecological theory of the digital world
      which exhibits stable coexistence of several networks as well as the dominance of
      an individual one, in contrast to the competitive exclusion principle.
      Interestingly, our theory also predicts that the most probable outcome is the
      coexistence of a moderate number of services, in agreement with empirical
      observations. 

PMID- 25988317
TI  - Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12
      week double-blind randomized controlled trial.
AB  - Low-dose memantine might have anti-inflammatory and neurotrophic effects
      mechanistically remote from an NMDA receptor. We investigated whether add-on
      memantine reduced cytokine levels and benefitted patients with opioid dependence
      undergoing methadone maintenance therapy (MMT) in a randomized, double-blind,
      controlled 12-week study. Patients were randomly assigned to a group: Memantine
      (5 mg/day) (n = 53) or Placebo (n = 75). The methadone dose required and
      retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-alpha,
      C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor
      (TGF)-beta1, and brain-derived neurotrophic factor (BDNF) levels were examined
      during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine
      therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower
      methadone dose than did Placebo-group (P = 0.039). They also had significantly
      lower plasma TNF-alpha and significantly higher TGF-beta1 levels. We provide
      evidence of the benefit of add-on memantine in opioid dependent patients
      undergoing MMT. 

PMID- 25988320
TI  - Synthesis of 2-aminoindolizines by 1,3-dipolar cycloaddition of pyridinium ylides
      with electron-deficient ynamides.
AB  - Electron-deficient ynamides, possessing an ynoate or an ynone moiety, have been
      successfully involved for the first time in a 1,3-dipolar cycloaddition with
      stabilized pyridinium ylides. These reactions afford an efficient and general
      access toward a variety of substituted 2-aminoindolizines which can serve as
      useful precursors for the synthesis of other more complex nitrogen heterocycles. 

PMID- 25988324
TI  - Can a single water molecule really affect the HO2 + NO2 hydrogen abstraction
      reaction under tropospheric conditions?
AB  - The effect of a single water molecule on the HO2 + NO2 hydrogen abstraction
      reaction has been investigated by employing B3LYP and CCSD(T) theoretical
      approaches with the aug-cc-pVTZ basis set. The reaction without water has three
      types of reaction channels on both singlet and triplet potential energy surfaces,
      depending on how the HO2 radical approaches NO2. These correspond to the
      formation of trans-HONO + O2, cis-HONO + O2 and HNO2 + O2. Our calculated results
      show that triplet reaction channels are favorable and their total rate constant,
      at 298 K, is 2.01 * 10(-15) cm(3) molecule(-1) s(-1), which is in good agreement
      with experimental values. A single water molecule affects each one of these
      triplet reaction channels in the three different reactions of H2O...HO2 + NO2,
      HO2...H2O + NO2 and NO2...H2O + HO2, depending on the way the water interacts.
      Interestingly, the water molecule in these reactions not only acts as a catalyst
      giving the same products as the naked reaction, but also as a reactant giving the
      product of HONO2 + H2O2. The total rate constant of the H2O...HO2 + NO2 reaction
      is estimated to be slower than the naked reaction by 6 orders of magnitude at 298
      K. However, the total rate constants of the HO2...H2O + NO2 and NO2...H2O + HO2
      reactions are faster than the naked reaction by 4 and 3 orders of magnitude at
      298 K, respectively. Their total effective rate constant is predicted to be 1.2
      times that of the corresponding total rate constant without water at 298 K, which
      is in agreement with the prediction reported by Li et al. (science, 2014, 344,
      292-296).

PMID- 25988326
TI  - Reducing the risk for waterborne nosocomial neonatal legionellosis.

PMID- 25988327
TI  - Why should hospitals fund delirium research?

PMID- 25988329
TI  - Revised AGS Choosing Wisely((r)) list: changes to help guide older adult care
      conversations.

PMID- 25988330
TI  - Rational design, synthesis and molecular modeling studies of novel anti
      oncological alkaloids against melanoma.
AB  - 3D-pharmacophore and 2D-QSAR modeling studies describe the anti-oncological
      properties of spiro-alkaloids. The dispiro[2H-indene-2,3'-pyrrolidine-2',3''
      [3H]indole]-1,2''(1''H, 3H)-diones 20-38 were prepared via 1,3-dipolar
      cycloaddition reactions of azomethine ylides (generated in situ via
      decarboxylative condensation of isatins 7-9 with sarcosine 10) and 2
      (arylmethylidene)-2,3-dihydro-1H-inden-1-ones 11-19 in refluxing ethanol. Some of
      the spiro-alkaloids (21, 22, 29 and 37) revealed potent antitumor properties
      against melanoma carcinoma cell lines (GaLa, LuPiCi and LuCa) utilizing the in
      vitro SRB standard method exhibiting potency close to that of the standard
      reference doxorubicin. 

PMID- 25988332
TI  - Flavor compounds and sensory profiles of a novel Chinese marinated chicken.
AB  - BACKGROUND: Marinating is a Chinese traditional meat-processing method using aged
      brine that brings popular flavor together with food safety issues. In this study
      a novel method named quantitative marinating (QM) was developed to improve
      Chinese traditional marinating (TM). Flavor compounds and sensory profiles of two
      marinated products were determined to verify if the improved marinating method
      could maintain the characteristic flavors of TM. RESULTS: Fifty-four, 60, 60, 60
      and 44 volatile flavor compounds were identified from four processing stages of
      QM and TM respectively. Contents of taste compounds first increased and then
      decreased in the processing stages of QM. The total free amino acid contents of
      QM and TM products were 789 and 536 mg per 100 g respectively. The total
      nucleotide content of QM product (22.21 mg per 100 g) was higher than that of TM
      (20.75 mg per 100 g), while the fatty acid content of QM product (26.66 mg g(-1))
      was lower than that of TM (44.43 mg g(-1)). Finally, QM received higher sensory
      scores than TM. CONCLUSION: Volatile flavor compounds, taste compounds and
      sensory properties of QM were richer than those of TM, indicating that QM can not
      only maintain the original aroma of TM but also have advantages in taste
      compounds.

PMID- 25988331
TI  - Sorting of Clathrin-Independent Cargo Proteins Depends on Rab35 Delivered by
      Clathrin-Mediated Endocytosis.
AB  - Clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) co
      exist in most cells but little is known about their communication and
      coordination. Here we show that when CME was inhibited, endocytosis by CIE
      continued but endosomal trafficking of CIE cargo proteins was altered. CIE cargo
      proteins that normally traffic directly into Arf6-associated tubules after
      internalization and avoid degradation (CD44, CD98 and CD147) now trafficked to
      lysosomes and were degraded. The endosomal tubules were also absent and Arf6-GTP
      levels were elevated. The altered trafficking, loss of the tubular endosomal
      network and elevated Arf6-GTP levels caused by inhibition of CME were rescued by
      expression of Rab35, a Rab associated with clathrin-coated vesicles, or its
      effector ACAPs, Arf6 GTPase activating proteins (GAP) that inactivate Arf6.
      Furthermore, siRNA knockdown of Rab35 recreated the phenotype of CME ablation on
      CIE cargo trafficking without altering endocytosis of transferrin. These
      observations suggest that Rab35 serves as a CME detector and that loss of CME, or
      Rab35 input, leads to elevated Arf6-GTP and shifts the sorting of CIE cargo
      proteins to lysosomes and degradation. 

PMID- 25988333
TI  - Accumulation of contaminants of emerging concern in food crops-part 1: Edible
      strawberries and lettuce grown in reclaimed water.
AB  - Contaminants of emerging concern present in domestic waste streams include a
      highly diverse group of potentially biologically active compounds that can be
      detected at trace levels in wastewater. Concerns about potential uptake into
      crops arise when reclaimed water is used in food crop production. The present
      study investigated how 9 contaminants of emerging concern in reclaimed water are
      taken up into edible portions of two food crops. Two flame retardant chemicals,
      tris(1-chloro-2-propyl) phosphate (TCPP) and tris(2-chloroethyl) phosphate (TCEP)
      and several polar pharmaceuticals (carbamazepine, diphenhydramine,
      sulfamethoxazole, and trimethoprim) accumulated in a linear, concentration
      dependent manner in lettuce (Lactuca sativa) irrigated with reclaimed water,
      suggesting passive uptake of both neutral and ionizable chemical contaminants in
      lettuce. Furthermore, concentration-dependent accumulation of TCEP and TCPP from
      reclaimed water was also observed in strawberry fruits (Fragaria ananassa).
      Collectively, these data suggest that highly polar or charged contaminants can be
      taken up by crops from water bearing contaminants of emerging concern and can be
      accumulated in the edible portions. Using these data, however, estimates of human
      exposure to these contaminants from reclaimed water food crop accumulation
      suggest that exposure to the contaminants of emerging concern examined in the
      present study is likely substantially lower than current exposure guidelines.

PMID- 25988319
TI  - Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes
      and are regulated by APOE.
AB  - Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but
      the impact of iron on disease outcomes has not been previously explored in a
      longitudinal study. Ferritin is the major iron storage protein of the body; by
      using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored
      whether brain iron status impacts longitudinal outcomes in the Alzheimer's
      Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin
      levels were negatively associated with cognitive performance over 7 years in 91
      cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and
      predicted MCI conversion to AD. Ferritin was strongly associated with CSF
      apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-E4.
      These findings reveal that elevated brain iron adversely impacts on AD
      progression, and introduce brain iron elevation as a possible mechanism for APOE
      E4 being the major genetic risk factor for AD. 

PMID- 25988334
TI  - Trivalent Cation Induced Bundle Formation of Filamentous fd Phages.
AB  - Bacteriophages are filamentous polyelectrolyte viral rods infecting only
      bacteria. In this study, we investigate the bundle formation of fd phages with
      trivalent cations having different ionic radii (Al(3+) , La(3+) and Y(3+) ) at
      various phage and counterion concentrations, and at varying bundling times.
      Aggregated phage bundles were detected at relatively low trivalent counterion
      concentrations (1 mM). Although 10 mM and 100 mM Y(3+) and La(3+) treatments
      formed larger and more intertwined phage bundles, Al(3+) and Fe(3+) treatments
      lead to the formation of networking filaments. Energy dispersive X-ray
      spectroscopy (EDX) analyses confirmed the presence of C, N and O peaks on densely
      packed phage bundles. Immunofluorescence labelling and ELISA analyses with anti
      p8 antibodies showed the presence of phage filaments after bundling. 

PMID- 25988335
TI  - miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition
      of the cell cycle and the epithelial to mesenchymal transition in cervical cancer
      cells.
AB  - MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate target gene
      expression, play an important role in cancer initiation, progression, and
      metastasis. However, the role of many miRNAs in cervical cancer is not fully
      understood. In this study, we found that miR-212 and miR-132 from the same gene
      cluster are downregulated in human cervical cancer tissues when compared with
      adjacent noncancerous tissues. The overexpression of miR-212/132 not only led to
      a delay in the G1/S phase transition and repressed cell proliferation but also
      resulted in an increase in E-cadherin expression and a decrease in vimentin,
      suppressing the epithelial to mesenchymal transition and migration and invasion
      in cervical cancer cells. Subsequently, SMAD2 was identified as a common target
      of miR-212/132 and was found to be negatively regulated by miR-212/132 at the
      mRNA and protein levels. Furthermore, SMAD2 silencing led to the same effect on
      cervical cancer cells as miR-212/132 overexpression. Importantly, SMAD2
      overexpression partially reversed the cellular phenotypes induced by miR-212/132
      overexpression. In conclusion, our study indicated that miR-212/132 functions as
      tumor suppressor by targeting SMAD2 in cervical cancer.

PMID- 25988336
TI  - Diagnostic value of panoramic radiography in predicting inferior alveolar nerve
      injury after mandibular third molar extraction: a meta-analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the predictive value of
      panoramic radiography on inferior alveolar nerve (IAN) injury after extraction of
      the mandibular third molar. METHODS: Relevant studies up to 1 June 2014 that
      discussed the association of panoramic radiography signs and post-mandibular
      third molar extraction IAN injury were systematically retrieved from the
      databases of PubMed, Embase, Springerlink, Web of Science and Cochrane library.
      The effect size of pooled sensitivity, specificity, positive likelihood ratios
      (PLR), negative likelihood ratios (NLR) and diagnostic odds ratio (DOR) with
      their 95% confidence intervals (CI) were statistically analysed with Meta-disc
      1.4 software. RESULTS: Nine articles were included in this meta-analysis. The
      pooled estimates of sensitivity and specificity were 0.56 (95% CI: 0.50-0.61) and
      0.86 (95% CI: 0.84-0.87), respectively. The overall PLR was 3.46 (95% CI: 2.02
      5.92) and overall NLR was 0.58 (95% CI: 0.45-0.73). The pooled estimate of DOR
      was 6.49 (95% CI: 2.92-14.44). The area under the summary receiver operating
      characteristic curve was 0.7143 +/- 0.0604. CONCLUSIONS: The meta-analysis
      indicated that interpretation of panoramic radiography based on darkening of the
      root had a high specificity in predicting IAN injury after mandibular third molar
      extraction. However, the ability of this panoramic radiography marker to detect
      true positive IAN injury was not satisfactory.

PMID- 25988337
TI  - Mycosis fungoides and Sezary syndrome: Current challenges in assessment,
      management and prognostic markers.
AB  - Mycosis fungoides and Sezary syndrome are the most common variants of the
      cutaneous T-cell lymphomas. Assessment of a patient with a suspected diagnosis
      requires thorough history taking and physical examination, in combination with
      skin biopsy. In some cases flow cytometry, molecular studies and imaging are also
      required in order to diagnose and stage the disease. Staging is derived from the
      tumour-node-metastasis-blood classification and is currently our best attempt to
      stratify prognosis and hence guide management in this complex disease. Many other
      clinical, biological and pathological factors may help to distinguish groups at
      risk and predict prognosis more accurately. Management remains heavily guided by
      staging, such that patients with early-stage disease generally begin treatment
      with skin-directed or local therapies and those with advanced-stage disease have
      many treatment options, including chemotherapy, the use of biological agents,
      local and total body radiotherapy, as well as haematopoietic stem cell
      transplantation. Besides staging, many other patient-related factors influence
      the treatment strategy, particularly where symptom relief is paramount. There are
      many challenges remaining in the study of Mycosis fungoides and Sezary syndrome
      and, given the rarity of the disease, concerted worldwide efforts are required to
      conduct efficient and effective research. 

PMID- 25988338
TI  - Improved T1, contrast concentration, and pharmacokinetic parameter quantification
      in the presence of fat with two-point Dixon for dynamic contrast-enhanced
      magnetic resonance imaging.
AB  - PURPOSE: To evaluate the impact of fat and fat-suppression on the quantification
      of T1, gadolinium concentration, and pharmacokinetic parameters in DCE-MRI.
      METHODS: T1 values were measured in fat-free phantoms using variable flip angle
      with no fat suppression, quick or interleaved fat saturation (QFS), or two-point
      Dixon and were compared with reference values measured with inversion recovery
      prepared turbo spin echo. Relaxivity of gadolinium-benzyloxypropionictetraacetate
      (Gd-BOPTA) was measured in emulsions of Gd-BOPTA solution and fat using Dixon in
      phase and water-only images. Liver T1 and pharmacokinetic parameters of 15
      patients were calculated from Dixon in-phase and water-only images and were
      correlated with liver fat signal fraction. RESULTS: T1 values measured using
      Dixon water-only and non-fat-suppressed images matched the reference values;
      while T1 values measured using QFS showed large deviations. Relaxivities and Gd
      measured in the Dixon water-only images were less affected by the fat than those
      measured in the in-phase images. The correlation between liver fat fraction and
      the differences in measured pharmacokinetic parameters using Dixon in-phase and
      water-only images were significant (P < 0.05) for T1, K(trans), and incremental
      area under the curve, but not Ve (P = 0.1). CONCLUSION: Dixon water-only images
      provided more reliable estimation of T1, Gd, and pharmacokinetic parameters when
      fat was present.

PMID- 25988340
TI  - Do we need a disease-specific cardiovascular risk calculator for patients with
      rheumatoid arthritis?

PMID- 25988339
TI  - Gut metabolites and bacterial community networks during a pilot intervention
      study with flaxseeds in healthy adult men.
AB  - SCOPE: Flaxseeds contain the phytoestrogens lignans that must be activated to
      enterolignans by intestinal bacteria. We investigated the impact of flaxseeds on
      fecal bacterial communities and their associations with fecal and blood
      metabolites. METHODS AND RESULTS: Nine healthy male adult subjects ingested 0.3
      g/kg/day flaxseeds during 1 week. Gut bacteria as well as blood and fecal
      metabolites were analyzed. Ingestion of flaxseeds triggered a significant
      increase in the blood concentration of enterolignans, accompanied by fecal
      excretion of propionate and glycerol. Overall diversity and composition of
      dominant fecal bacteria remained individual specific throughout the study.
      Enterolactone production was linked to the abundance of two molecular species
      identified as Ruminococcus bromii and Ruminococcus lactaris. Most dominant
      species of the order Bacteroidales were positively associated with fecal
      concentrations of either acetic, isovaleric, or isobutyric acid, the latter being
      negatively correlated with blood levels of triglycerides. The relative sequence
      abundance of one Gemmiger species (Ruminococcaceae) and of Coprococcus comes
      (Lachnospiraceae) correlated positively with blood levels of LDL cholesterol and
      triglycerides, respectively. CONCLUSION: Flaxseeds increase enterolignan
      production but do not markedly alter fecal metabolome and dominant bacterial
      communities. The data underline the possible role of members of the family
      Ruminococcaceae in the regulation of enterolignan production and blood lipids.

PMID- 25988341
TI  - Understanding and Reducing Inconsistency in Seatbelt-Use Decisions: Findings from
      a Cardinal Decision Issue Perspective.
AB  - This article has two aims. The first is to present results that partly explain
      why some automobile drivers choose to use their seatbelts only part time, thereby
      exposing themselves to unnecessary risk. The second is to offer and illustrate
      the "cardinal decision issue perspective"((1)) as a tool for guiding research and
      development efforts that focus on complex real-life decision behaviors that can
      entail wide varieties of risk, including but not limited to inconsistent seatbelt
      use. Each of 24 young male participants drove an instrumented vehicle equipped to
      record continuously seatbelt use as well as other driving data. After all trips
      were finished, each participant completed an interview designed to reconstruct
      how he made randomly selected seatbelt-use decisions under specified conditions.
      The interview also examined whether and how drivers established "decision
      policies" regarding seatbelt use. Such policies were good predictors of
      inconsistent seatbelt use. Drivers who had previously adopted policies calling
      for consistent seatbelt use were significantly more likely than others to
      actually drive belted. Meta-decisions about seatbelt policy adoption appeared to
      rest on factors such as whether the driver had ever been asked to consider
      selecting a policy. Whether a driver made an ad hoc, on-the-spot seatbelt-use
      decision was associated with a perceived need to make such a decision. Finally,
      participants with full-time policies were especially likely to deploy their
      seatbelts by default, without recognizing the need to decide about belt use on a
      trip-by-trip basis. We end with recommendations for reducing inconsistencies in
      seatbelt use in actual practice. 

PMID- 25988342
TI  - Exciting potential: the importance of the right environment.

PMID- 25988343
TI  - Handling low hemoglobin and iron deficiency in a blood donor population: 2 years'
      experience.
AB  - BACKGROUND: Iron deficiency and blood donors with low hemoglobin (Hb)
      concentration are well-known challenges in any blood bank setting. In the Capital
      Region of Denmark, a new approach was adopted that centralized measurement of Hb,
      initiated ferritin (F) measurement, and established a center for donor Hb and
      iron. An algorithm was created based on Hb and F levels, which drove decisions on
      outreach by the donor Hb and iron resource team to the donor, including whether
      to provide iron supplementation or, on rare occasions, a referral to the donor's
      general practitioner. STUDY DESIGN AND METHODS: The change in Hb for repeat
      donors was followed during the first 2 years of the intervention strategy, which
      included measurements of F and offering intermittent iron supplementation to some
      of the donors. RESULTS: In 2 years, 62,663 blood donors donated 193,288 units of
      blood and 318 donors gave 754 complete blood count blood samples. Over time in
      the repeat donors, the Hb increased from 15.39 to 15.60 g/dL and 13.85 to 14.06
      g/dL in male and female donors, respectively, and the proportion of donors with
      low Hb decreased from 0.9% to 0.3% and 3.9% to 2.7% for the male and female
      donors, respectively. CONCLUSION: The program with goal-directed iron
      supplementation only to those that would benefit has led to an increase in Hb
      concentration and a reduction in the proportion of donors with low Hb
      concentration.

PMID- 25988345
TI  - Outburst of Macrophage Activation Syndrome in Mevalonate Kinase Deficiency:
      Comment on the Article by Schulert et al.

PMID- 25988346
TI  - Fetal umbilical-portal-systemic venous shunt: in-utero classification and
      clinical significance.
AB  - OBJECTIVES: To review our experience with fetal umbilical-portal-systemic venous
      shunts (UPSVS), to devise an in-utero classification system, and to analyze their
      clinical and prognostic characteristics. METHODS: This was a retrospective review
      of cases of UPSVS examined at an academic tertiary referral center over the 14
      year period from 2001 to 2014 inclusive. The anatomical origin and drainage of
      the fetal umbilical, portal, ductus venosus and hepatic venous systems, and the
      integrity of the intrahepatic portal venous system (IHPVS), were assessed using
      two- and three-dimensional color Doppler sonography. Fetomaternal clinical
      characteristics and long-term outcome were investigated by means of medical
      files, imaging documentation and telephone interviews with the mothers. RESULTS:
      Forty-four cases with UPSVS were reviewed. Prenatal classification was based on
      the anatomical origin of the shunt (umbilical, portal or ductal), with cases
      classified into four types: Type I, umbilical-systemic shunt (n = 9 (20.4%));
      Type II, ductus venosus-systemic shunt (n = 19 (43.2%)); and Type III, portal
      systemic shunt, divided into two subtypes: Type IIIa, intrahepatic portal
      systemic shunt (n = 12 (27.2%)) and Type IIIb, extrahepatic portal-systemic shunt
      (n = 4 (9.1%)). Each type presented particular clinical and prognostic
      characteristics. The most important favorable prognostic factors were absence of
      associated major malformation and presence of the IHPVS. Thus, Type IIIa
      (intrahepatic portal-systemic shunt) had the best outcome. CONCLUSIONS: Fetal
      UPSVS are anomalies with a broad spectrum of manifestations and prognoses.
      Accurate mapping of the IHPVS is paramount for optimizing prenatal counseling and
      postnatal care. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 25988347
TI  - Navigating the mesentery: a comparative pre- and per-operative visualization of
      the vascular anatomy.
AB  - AIM: Awareness of anatomy is critical for performing safe surgery within the root
      of the mesentery. Our aim was to investigate the anatomical relationship between
      the superior mesenteric artery (SMA) and vein (SMV) and their branches within a
      predefined D3 area of the right colon and to compare preoperatively established
      three-dimensional (3D) mesenteric vessel anatomy from CT with that found at
      surgery. METHOD: Prospective data were collected on 139 patients included in the
      'Safe Radical D3 Right Hemicolectomy for Cancer Through Preoperative Biphasic
      Multi-detector Computed Tomography (MDCT) Angiography' trial. CT data sets were
      3D reconstructed before surgery and compared with photographs taken during the
      operation. RESULTS: The ileocolic artery was present and correctly identified in
      all patients and crossed the SMV anteriorly in 58 (41.7%). Seventeen patients had
      a right colic artery at surgery and there were three false-negative and one false
      positive CT findings, yielding a diagnostic accuracy of 97.1%, sensitivity of
      85.7% and specificity of 95.2%. Positive and negative predictive values were
      94.7% and 97.5%, respectively. The middle colic artery was absent in one (0.7%)
      patient and multiple (nine double and one triple) in 10 (7.2%) patients. A mean
      of 3.8 +/- 1.2 jejunal arteries and 2.0 +/- 0.8 jejunal veins arose from the SMA
      and SMV. Jejunal veins crossed the SMA in the D3 area anteriorly in 30.9% of
      patients. In 26 (18.7%) patients, additional veins drained into the SMV,
      including pancreaticoduodenal in 16, right colic in six and both in two. The
      inferior mesenteric vein entered the SMV in 58 (41.7%) patients and crossed the
      D3 area in three (2.2%). CONCLUSION: CT-reconstructed anatomy has high
      specificity, sensitivity, accuracy and reliability.

PMID- 25988348
TI  - Prospective multicenter international surveillance of azole resistance in
      Aspergillus fumigatus.
AB  - To investigate azole resistance in clinical Aspergillus isolates, we conducted
      prospective multicenter international surveillance. A total of 3,788 Aspergillus
      isolates were screened in 22 centers from 19 countries. Azole-resistant A.
      fumigatus was more frequently found (3.2% prevalence) than previously
      acknowledged, causing resistant invasive and noninvasive aspergillosis and
      severely compromising clinical use of azoles. 

PMID- 25988349
TI  - Treatment patterns in advanced melanoma: findings from a survey of European
      oncologists.
AB  - With the emergence of new therapies, established patterns of treating advanced
      melanoma are changing. The aim of this study was to understand how advanced
      melanoma is treated in clinical practice in Europe following the introduction of
      ipilimumab and vemurafenib. An online survey was conducted between August and
      November 2012 with 150 oncologists and dermatologists, from France, Germany,
      Italy, Spain and the U.K.; respondents reported treating the majority of patients
      with one or two lines of therapy. For BRAF mutant melanoma, the most frequently
      used first-line treatments were vemurafenib and dacarbazine. For BRAF wild-type
      melanoma, the most frequently used first-line treatment was dacarbazine. There
      was no single preferred agent for the second-line treatment of BRAF mutant or
      BRAF wild-type disease. Most sequencing from first- to second-line was from
      conventional dacarbazine to newer agents such as ipilimumab and vemurafenib. The
      treatment of advanced melanoma is rapidly evolving due to the introduction of new
      agents. This study presents an early insight into access to the new agents,
      ipilimumab and vemurafenib, and clinical practice in several European countries.

PMID- 25988350
TI  - Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events
      following Vaccination, Haiti, 2013.
AB  - In 2013, the first government-led oral cholera vaccination (OCV) campaign in
      Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination
      coverage, barriers to vaccination, and adverse events following vaccination, we
      conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809
      persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years).
      Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two
      dose coverage was lowest among persons >15 years of age. In Cerca Carvajal,
      coverage was significantly lower for male than female respondents (69% vs. 85%;
      p<0.001). No major adverse events were reported. The main reason for
      nonvaccination was absence during the campaign. Vaccination coverage after this
      campaign was acceptable and comparable to that resulting from campaigns
      implemented by nongovernmental organizations. Future campaigns should be tailored
      to reach adults who are not available during daytime hours. 

PMID- 25988352
TI  - DFT calculations of magnetic anisotropy energy of Ge(1-x)Mn(x)Te ferromagnetic
      semiconductor.
AB  - Density functional theory (DFT) calculations of the energy of magnetic anisotropy
      for diluted ferromagnetic semiconductor Ge(1-x)Mn(x)Te were performed using
      OpenMX package with fully relativistic pseudopotentials. The influence of hole
      concentration and magnetic ion neighbourhood on magnetic anisotropy energy is
      presented. Analysis of microscopic mechanism of magnetic anisotropy is provided,
      in particular the role of spin-orbit coupling, spin polarization and spatial
      changes of electron density are discussed. The calculations are in accordance
      with the experimental observation of perpendicular magnetic anisotropy in
      rhombohedral Ge(1-x)Mn(x)Te (1 1 1) thin layers.

PMID- 25988351
TI  - A Method for Extracting the Free Energy Surface and Conformational Dynamics of
      Fast-Folding Proteins from Single Molecule Photon Trajectories.
AB  - Single molecule fluorescence spectroscopy holds the promise of providing direct
      measurements of protein folding free energy landscapes and conformational
      motions. However, fulfilling this promise has been prevented by technical
      limitations, most notably, the difficulty in analyzing the small packets of
      photons per millisecond that are typically recorded from individual biomolecules.
      Such limitation impairs the ability to accurately determine conformational
      distributions and resolve sub-millisecond processes. Here we develop an
      analytical procedure for extracting the conformational distribution and dynamics
      of fast-folding proteins directly from time-stamped photon arrival trajectories
      produced by single molecule FRET experiments. Our procedure combines the maximum
      likelihood analysis originally developed by Gopich and Szabo with a statistical
      mechanical model that describes protein folding as diffusion on a one-dimensional
      free energy surface. Using stochastic kinetic simulations, we thoroughly tested
      the performance of the method in identifying diverse fast-folding scenarios,
      ranging from two-state to one-state downhill folding, as a function of relevant
      experimental variables such as photon count rate, amount of input data, and
      background noise. The tests demonstrate that the analysis can accurately retrieve
      the original one-dimensional free energy surface and microsecond folding dynamics
      in spite of the sub-megahertz photon count rates and significant background noise
      levels of current single molecule fluorescence experiments. Therefore, our
      approach provides a powerful tool for the quantitative analysis of single
      molecule FRET experiments of fast protein folding that is also potentially
      extensible to the analysis of any other biomolecular process governed by sub
      millisecond conformational dynamics. 

PMID- 25988353
TI  - Human Herpesvirus 8-Related Primary Effusion Lymphoma After Liver
      Transplantation.
AB  - Primary effusion lymphoma is a rare subclass of non-Hodgkin lymphoma associated
      with human herpesvirus 8 infection and principally seen in human immunodeficiency
      virus-positive patients. We report on the case of a 72-year-old human
      immunodeficiency virus-negative male with a hepatic transplant 10 years prior,
      who presented with a symptomatic right-sided pleural effusion and was found to
      have primary effusion lymphoma by flow cytometric and cytopathologic examination.
      Immunohistochemistry of his lymphoma cells was positive for human herpesvirus 8.
      Both he and his donor had no identifiable risk factors for human herpesvirus 8
      infection. The patient was intolerant of antiviral therapy and chemotherapy,
      dying 7 months after diagnosis. Posttransplant primary effusion lymphoma is
      exceedingly rare and carries a very poor prognosis. Individualized treatment
      strategies are necessary given the scant body of published literature with
      guidance based solely on case reports. 

PMID- 25988354
TI  - Highly Selective Dissociation of a Peptide Bond Following Excitation of Core
      Electrons.
AB  - The controlled breaking of a specific chemical bond with photons in complex
      molecules remains a major challenge in chemistry. In principle, using the K-edge
      absorption of a particular atomic element, one might excite selectively a
      specific atomic entity in a molecule. We report here highly selective
      dissociation of the peptide bonds in N-methylformamide and N-methylacetamide on
      tuning the X-ray wavelength to the K-edge absorption of the atoms connected to
      (or near) the peptide bond. The high selectivity (56-71%) of this cleavage arises
      from the large energy shift of X-ray absorption, a large overlap of the 1s
      orbital and the valence pi* orbital that is highly localized on a peptide bond
      with antibonding character, and the relatively low bond energy of the peptide
      bonds. These characteristics indicate that the high selectivity on bond
      dissociation following core excitation could be a general feature for molecules
      containing peptide bonds. 

PMID- 25988355
TI  - Nucleoid organization in the radioresistant bacterium Deinococcus radiodurans.
AB  - Processes favoring the exceptional resistance to genotoxic stress of Deinococcus
      radiodurans are not yet completely characterized. It was postulated that its
      nucleoid and chromosome(s) organization could participate in the DNA double
      strand break repair process. Here, we investigated the organization of chromosome
      1 by localization of three chromosomal loci including oriC, Ter and a locus
      located in its left arm. For this purpose, we used a ParB-parS system to
      visualize the position of the loci before and after exposure to gamma-rays. By
      comparing the number of fluorescent foci with the number of copies of the studied
      loci present in the cells measured by quantitative polymerase chain reaction
      (qPCR), we demonstrated that the 4-10 copies of chromosome 1 per cell are
      dispersed within the nucleoid before irradiation, indicating that the chromosome
      copies are not prealigned. Chromosome segregation is progressive but not co
      ordinated, allowing each locus to be paired with its sister during part of the
      cell cycle. After irradiation, the nucleoid organization is modified, involving a
      transient alignment of the loci in the late stage of DNA repair and a delay of
      segregation of the Ter locus. We discuss how these events can influence DNA
      double strand break repair. 

PMID- 25988356
TI  - FERONIA receptor kinase interacts with S-adenosylmethionine synthetase and
      suppresses S-adenosylmethionine production and ethylene biosynthesis in
      Arabidopsis.
AB  - Environmental inputs such as stress can modulate plant cell metabolism, but the
      detailed mechanism remains unclear. We report here that FERONIA (FER), a plasma
      membrane receptor-like kinase, may negatively regulate the S-adenosylmethionine
      (SAM) synthesis by interacting with two S-adenosylmethionine synthases (SAM1 and
      SAM2). SAM participates in ethylene, nicotianamine and polyamine biosynthetic
      pathways and provides the methyl group for protein and DNA methylation reactions.
      The Arabidopsis fer mutants contained a higher level of SAM and ethylene in plant
      tissues and displayed a dwarf phenotype. Such phenotype in the fer mutants was
      mimicked by over-expressing the S-adenosylmethionine synthetase in transgenic
      plants, whereas sam1/2 double mutant showed an opposite phenotype. We propose
      that FER receptor kinase, in response to environmental stress and plant hormones
      such as auxin and BR, interacts with SAM synthases and down-regulates ethylene
      biosynthesis. 

PMID- 25988357
TI  - ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is
      required for fear memory.
AB  - Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit
      (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both
      fear learning and activity-induced long-term potentiation (LTP) of cortico
      basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting
      a critical role of ASICs in fear memory formation. In this study, we found that
      ASICs were differentially expressed within the amygdala neuronal population, and
      the extent of LTP at various glutamatergic synapses correlated with the level of
      ASIC expression in postsynaptic neurons. Importantly, selective deletion of
      ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in
      these cells and reduced fear learning to the same extent as that found when
      ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear
      learning requires ASIC-dependent LTP at multiple amygdala synapses, including
      both cortico-BLA input synapses and intra-amygdala synapses on output neurons. 

PMID- 25988360
TI  - Sex differences in mechanisms, presentation and management of ischaemic heart
      disease.
AB  - Ischaemic heart disease (IHD) is the leading cause of death in women as in men,
      although presentation in women is on average 7-10 years later. Recent temporal
      trends show declining IHD incidence and mortality among men but not among women.
      Other gender differences concern the prevalence of underlying mechanisms. Women
      more frequently than men have nonobstructive epicardial artery disease,
      nonatherosclerotic spontaneous coronary artery dissection, stress cardiomyopathy,
      plaque erosion, microvascular dysfunction, and a heavier risk factor burden, even
      after adjustment for age. Atypical symptoms of IHD are more common in women. The
      crude outcomes of both chronic and acute coronary syndromes are worse in women
      than in men, in relation to older age and comorbidities. After adjustments, in
      hospital mortality after acute myocardial infarction is reported to remain higher
      among younger women compared to male peers. Such female vulnerability, in
      apparent contrast with the delayed average onset and lesser extent of epicardial
      atherosclerosis, likely reflects gender differences in early presentation, as
      well as in mechanisms, prevention, diagnosis, comorbidities, management, and
      response to treatment. Recognition and quality of care of IHD are still not the
      same for women and men. 

PMID- 25988358
TI  - Advanced fibrosis associates with atherosclerosis in subjects with nonalcoholic
      fatty liver disease.
AB  - OBJECTIVE: Nonalcoholic fatty liver (NAFLD) with advanced fibrosis usually has a
      deteriorated prognosis, which was mainly attributed to cardiovascular cause. We
      investigated whether advanced fibrosis assessed by noninvasive fibrosis markers
      was associated with subclinical atherosclerosis in NAFLD patients. METHODS: A
      total of 2550 participants with ultrasound confirmed NAFLD from a community based
      population study were included in the present analysis. NAFLD fibrosis score
      (NFS) derived from available parameters was calculated to assess severity of
      fibrosis of the NAFLD patients. The NAFLD patients with a NFS > 0.676 indicated
      of presence of advanced fibrosis. The carotid intima-media thickness (CIMT),
      carotid plaques and brachial-ankle pulse wave velocity (ba-PWV) were used as the
      indicators of early atherosclerosis. RESULTS: NAFLD patients with advanced
      fibrosis had higher CIMT and ba-PWV, compared with those without fibrosis (CIMT:
      0.65 versus 0.57 mm; ba-PWV: 1884 versus 1535 cm/s, both p < 0.0001).
      Participants with advanced fibrosis were more likely to have higher homeostasis
      model assessment of insulin resistance index (HOMA_IR, 3.28 versus 2.45, p <
      0.0001). After adjusting the confounders, participants with advanced fibrosis
      associated with 1.98-folds increased risk for elevated CIMT, 2.28-folds increased
      risk for present carotid plaque and 2.68-folds increased risk for arterial
      stiffness, respectively, as compared to participants without fibrosis. After
      further adjustment for HOMA_IR, the positive associations did not appreciably
      change. CONCLUSION: Advanced fibrosis indicated by NFS was positively associated
      with CIMT, presence of carotid plaque and arterial stiffness in the NAFLD
      patients, independent of conventional cardiometabolic risk factors and insulin
      resistance.

PMID- 25988359
TI  - Unfractionated heparin-clopidogrel combination in ST-elevation myocardial
      infarction not receiving reperfusion therapy.
AB  - OBJECTIVE: We sought explore the relative benefits of unfractionated heparin
      (UFH) compared with enoxaparin, alone or in combination with clopidogrel, in ST
      segment elevation myocardial infarction (STEMI) patients not undergoing
      reperfusion therapy. METHODS: This is a propensity score study from The
      International Survey on Acute Coronary Syndromes in Transition Countries (ISACS
      TC/NCT01218776) on patients admitted between October 2010-June 2013. There were a
      total of 1175 STEMI patients who did not receive mechanical or pharmacological
      reperfusion. Of these, 1063 were eligible for the aim of the study, being treated
      with UFH (522/1175; 44.4%) or enoxaparin (541/1175; 46%). Clopidogrel in
      combination with UFH or enoxaparin was given to 751 (63.9%) patients. The primary
      endpoint was in-hospital mortality. Secondary endpoints were intracranial
      hemorrhages, and clinically relevant bleedings. RESULTS: After adjustment for any
      confounders, UFH was associated with a lower risk of in-hospital mortality in
      clopidogrel users (multivariate adjusted regression analysis: odds ratio [OR]:
      0.62, 95% Confidence Interval [CI] 0.41-0.94) as compared with clopidogrel non
      users (OR: 0.94, 95% CI 0.55-1.60). The observed effect was not associated with
      combined enoxaparin and clopidogrel therapy. Major bleeding events were
      comparable in the enoxaparin group and UFH group (0.4% and 1.5% respectively, p =
      0.06). The risk of major hemorrhage was nearly similar with combined UFH
      clopidogrel therapy (1.4%) as compared with UFH alone (1.9%), p = 0.67.
      CONCLUSION: UFH - Clopidogrel combination was associated with a large mortality
      reduction in STEMI patients not undergoing reperfusion therapy and did not
      significantly increase the risk of major bleeding.

PMID- 25988363
TI  - Relationship of the Topological Distances and Activities between mPGES-1 and COX
      2 versus COX-1: Implications of the Different Post-Translational Endoplasmic
      Reticulum Organizations of COX-1 and COX-2.
AB  - In vascular inflammation, prostaglandin E2 (PGE2) is largely biosynthesized by
      microsomal PGE2 synthase-1 (mPGES-1), competing with other downstream eicosanoid
      synthesizing enzymes, such as PGIS, a synthase of a vascular protector
      prostacyclin (PGI2), to isomerize the cyclooxygenase (COX)-2-derived
      prostaglandin H2 (PGH2). In this study, we found that a majority of the product
      from the cells co-expressing human COX-2, mPGES-1, and PGIS was PGE2. We
      hypothesize that the molecular and cellular mechanisms are related to the post
      translational endoplasmic reticulum (ER) arrangement of those enzymes. A set of
      fusion enzymes, COX-2-linker [10 amino acids (aa)]-PGIS and COX-2-linker (22
      amino acids)-PGIS, were created as "The Bioruler", in which the 10 and 22 amino
      acids are defined linkers with known helical structures and distances (14.4 and
      30.8 A, respectively). Our experiments have shown that the efficiency of PGI2
      biosynthesis was reduced when the separation distance increased from 10 to 22
      amino acids. When COX-2-10aa-PGIS (with a 14.4 A separation) was co-expressed
      with mPGES-1 on the ER membrane, a major product was PGE2, but not PGI2. However,
      expression of COX-2-10aa-PGIS and mPGES-1 on a separated ER with a distance of
      ?30.8 A reduced the level of PGE2 production. These data indicated that the mPGES
      1 is "complex-likely" colocalized with COX-2 within a distance of 14.4 A. In
      addition, the cells co-expressing COX-1-10aa-PGIS and mPGES-1 produced PGI2
      mainly, but not PGE2. This indicates that mPGES-1 is expressed much farther from
      COX-1. These findings have led to proposed models showing the different post
      translational ER organization between COX-2 and COX-1 with respect to the
      topological arrangement of the mPGES-1 during vascular inflammation.

PMID- 25988361
TI  - Analysis of Published Criteria for Clinically Inactive Disease in a Large
      Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated.
AB  - OBJECTIVE: The Pediatric Rheumatology International Trials Organisation (PRINTO)
      recently published criteria for classification of patients with juvenile
      dermatomyositis (DM) as having clinically inactive disease. The criteria require
      that at least 3 of 4 conditions be met, i.e., creatine kinase level <=150
      units/liter, Childhood Myositis Assessment Scale score >=48, Manual Muscle
      Testing in 8 muscles score >=78, and physician's global assessment of overall
      disease activity (PGA) <=0.2. The present study was undertaken to test these
      criteria in a UK cohort of patients with juvenile DM. METHODS: We assessed 1,114
      patient visits for the 4 items in the PRINTO criteria for clinically inactive
      disease. Each visit was analyzed to determine whether skin disease was present.
      The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients.
      RESULTS: At 307 of the 1,114 visits, clinically inactive disease was achieved
      based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at
      65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA
      <=0.2 was one of the 3 criteria that were met, the frequency of skin signs was
      significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%).
      If PGA was considered an essential criterion for clinically inactive disease (P
      CID), patients with active skin disease were less likely to be categorized as
      having clinically inactive disease (a median DAS skin score of 0 [of a possible
      maximum of 9] in visits where the PGA was <=0.2, versus a median DAS skin score
      of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001).
      Use of the P-CID led to improvements in the positive predictive value and the
      positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and
      5.1 with the current criteria). CONCLUSION: There was a high frequency of skin
      disease among patients with juvenile DM who did not meet the PGA criterion for
      inactive disease but met the other 3 criteria. Incorporating PGA as an essential
      criterion for clinically inactive disease helps prevent the misclassification of
      patients with active skin disease.

PMID- 25988364
TI  - High Photoresponsivity and Short Photoresponse Times in Few-Layered WSe2
      Transistors.
AB  - Here, we report the photoconducting response of field-effect transistors based on
      three atomic layers of chemical vapor transport grown WSe2 crystals mechanically
      exfoliated onto SiO2. We find that trilayered WSe2 field-effect transistors,
      built with the simplest possible architecture, can display high hole mobilities
      ranging from 350 cm(2)/(V s) at room temperature (saturating at a value of ~500
      cm(2)/(V s) below 50 K) displaying a strong photocurrent response, which leads to
      exceptionally high photoresponsivities up to 7 A/W under white light illumination
      of the entire channel for power densities p < 10(2) W/m(2). Under a fixed
      wavelength of lambda = 532 nm and a laser spot size smaller than the conducting
      channel area, we extract photoresponsitivities approaching 100 mA/W with
      concomitantly high external quantum efficiencies up to ~40% at room temperature.
      These values surpass values recently reported from more complex architectures,
      such as graphene and transition metal dichalcogenides based heterostructures.
      Also, trilayered WSe2 phototransistors display photoresponse times on the order
      of 10 MUs. Our results indicate that the addition of a few atomic layers
      considerably decreases the photoresponse times, probably by minimizing the
      interaction with the substrates, while maintaining a very high photoresponsivity.

PMID- 25988362
TI  - Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal
      neuroinflammation in rat model of monoarthritis.
AB  - Curcumin is a major component of turmeric and reportedly has anti-inflammatory
      and anti-oxidant effects. Neuroinflammation has been recognized to play an
      important role in the pathogenesis of various diseases in the central nervous
      system. Here we investigated the anti-nociceptive and anti-neuroinflammatory
      effect of curcumin on arthritic pain in rats. We found that repeated oral
      treatment with curcumin, either before or after complete Freund's adjuvant (CFA)
      injection, dose-dependently attenuated CFA-induced mechanical allodynia and
      thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal
      injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore,
      such a curcumin treatment reduced CFA-induced activation of glial cells and
      production of inflammatory mediators [interleukin-1beta (IL-1beta), monocyte
      chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP
      1alpha)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced
      production of IL-1beta, tumor necrosis factor-alpha, MCP-1, and MIP-1alpha in
      cultured astrocytes and microglia. Our results suggest that intrathecal curcumin
      attenuates arthritic pain by inhibiting glial activation and the production of
      inflammatory mediators in the spinal cord, suggesting a new application of
      curcumin for the treatment of arthritic pain. 

PMID- 25988365
TI  - Bothersome tics in patients with chronic tic disorders: Characteristics and
      individualized treatment response to behavior therapy.
AB  - This report examined the most frequently reported bothersome tics among
      individuals with chronic tic disorders and evaluated the improvement and
      remission of tics and their associated characteristics. Youths and adults (N =
      240) were randomly assigned to receive the comprehensive behavioral intervention
      for tics (CBIT) or psychoeducation and supportive therapy (PST). At baseline,
      motor tics and tics with an urge were rated as more bothersome relative to vocal
      tics and tics without premonitory urges. The five most common bothersome tics
      included eye blinking, head jerks, sniffing, throat clearing, and other complex
      motor tics. While CBIT outperformed PST across tic type and urge presence, tics
      preceded by premonitory urges at baseline had higher severity at posttreatment
      across treatment condition. Six individual tic types had lower severity at
      posttreatment following CBIT relative to PST. Baseline urge presence was
      associated with tic remission for CBIT but not PST. Specific bothersome tics were
      more likely to remit with CBIT relative to PST. Findings suggest that individual
      tics respond and remit differently to CBIT relative to PST, with implications
      highlighting the negative reinforcement hypothesis in tic symptom maintenance.
      CLINICALTRIALS. GOV IDENTIFIERS: NCT00218777; NCT00231985.

PMID- 25988367
TI  - Band-like lipoatrophy on the forearm by injected triamcinolone acetonide to wrist
      joint.

PMID- 25988366
TI  - Targeted DNA degradation using a CRISPR device stably carried in the host genome.
AB  - Once an engineered organism completes its task, it is useful to degrade the
      associated DNA to reduce environmental release and protect intellectual property.
      Here we present a genetically encoded device (DNAi) that responds to a
      transcriptional input and degrades user-defined DNA. This enables engineered
      regions to be obscured when the cell enters a new environment. DNAi is based on
      type-IE CRISPR biochemistry and a synthetic CRISPR array defines the DNA
      target(s). When the input is on, plasmid DNA is degraded 10(8)-fold. When the
      genome is targeted, this causes cell death, reducing viable cells by a factor of
      10(8). Further, the CRISPR nuclease can direct degradation to specific genomic
      regions (for example, engineered or inserted DNA), which could be used to
      complicate recovery and sequencing efforts. DNAi can be stably carried in an
      engineered organism, with no impact on cell growth, plasmid stability or DNAi
      inducibility even after passaging for >2 months. 

PMID- 25988369
TI  - Systematic review of vision-related quality of life questionnaires for older
      institutionalised seniors with dementia.
AB  - PURPOSE: In view of our interest in helping older institutionalised adults with
      co-existing visual and cognitive deficits, our objective was to review vision
      related quality of life (VRQoL) questionnaires developed for people with
      dementia. METHODS: A systematic literature search was performed in seven relevant
      databases, limited to peer-reviewed journals published in English, French,
      Spanish, Italian or German languages, between 1982 and 2012. The retained VRQoL
      questionnaires were described. Only relevant articles that fully meet our target
      population and interest criteria were eligible for psychometric properties
      rating. RESULTS: The literature search identified 461 potentially relevant
      articles, from which 69 were isolated and reviewed. Eight articles presented
      questionnaires that were administered to older institutionalised individuals with
      dementia. Three VRQoL questionnaires were identified, from which only one was
      designed and validated for those with mild to moderate dementia and none for
      individuals with more advanced dementia. CONCLUSIONS: There is a pressing need to
      build and validate a questionnaire for assessing VRQoL in older institutionalised
      individuals with dementia, to provide a research tool capable of evaluating how
      changes in vision impact their QoL.

PMID- 25988370
TI  - Eutectic nano-droplet template injection into bulk silicon to construct porous
      frameworks with concomitant conformal coating as anodes for Li-ion batteries.
AB  - Building porosity in monolithic materials is highly desired to design 3D
      electrodes, however ex-situ introduction or in-situ generation of nano-scale
      sacrificial template is still a great challenge. Here Al-Si eutectic droplet
      templates are uniformly injected into bulk Si through Al-induced solid-solid
      convection to construct a highly porous Si framework. This process is concomitant
      with process-inherent conformal coating of ion-conductive oxide. Such an all-in
      one method has generated a (continuously processed) high-capacity Si anode
      integrating longevity and stable electrolyte-anode diaphragm for Li-ion batteries
      (e.g. a reversible capacity as large as ~1800 mAh/g or ~350 MUAh/cm(2)-MUm with a
      CE of ~99% at 0.1 C after long-term 400 cycles). 

PMID- 25988368
TI  - Protective role of bacillithiol in superoxide stress and Fe-S metabolism in
      Bacillus subtilis.
AB  - Glutathione (GSH) serves as the prime thiol in most organisms as its depletion
      increases antibiotic and metal toxicity, impairs oxidative stress responses, and
      affects Fe and Fe-S cluster metabolism. Many gram-positive bacteria lack GSH, but
      instead produce other structurally unrelated yet functionally equivalent thiols.
      Among those, bacillithiol (BSH) has been recently identified in several low G+C
      gram-positive bacteria. In this work, we have explored the link between BSH and
      Fe-S metabolism in Bacillus subtilis. We have identified that B. subtilis lacking
      BSH is more sensitive to oxidative stress (paraquat), and metal toxicity (Cu(I)
      and Cd(II)), but not H2 O2 . Furthermore, a slow growth phenotype of BSH null
      strain in minimal medium was observed, which could be recovered upon the addition
      of selected amino acids (Leu/Ile and Glu/Gln), supplementation of iron, or
      chemical complementation with BSH disulfide (BSSB) to the growth medium.
      Interestingly, Fe-S cluster containing isopropylmalate isomerase (LeuCD) and
      glutamate synthase (GOGAT) showed decreased activities in BSH null strain.
      Deficiency of BSH also resulted in decreased levels of intracellular Fe
      accompanied by increased levels of manganese and altered expression levels of Fe
      S cluster biosynthetic SUF components. Together, this study is the first to
      establish a link between BSH and Fe-S metabolism in B. subtilis.

PMID- 25988371
TI  - Patient-provider communication about medication use at the community pharmacy
      counter.
AB  - OBJECTIVE: The objectives of this study were to, first, describe the information
      exchanged between pharmacy staff and patients about prescribed medication at the
      community pharmacy counter, and second, to investigate to what extent this met
      professional medication counselling guidelines. METHODS: Pharmaceutical
      encounters were videotaped in four community pharmacies in the Netherlands.
      Patients were included if they collected a prescription for their own use. An
      observation protocol, including the MEDICODE checklist, was used to analyse the
      video recordings. A distinction was made between first and repeat prescriptions.
      KEY FINDINGS: One hundred fifty-three encounters were videotaped. When dispensing
      first prescriptions, pharmacy staff provided most information on instructions how
      to use the medication (83.3%), form of the medication (71.4%) and treatment
      duration (42.9%). Topics for repeat prescriptions (such as the effects of the
      medication and the incidence of observed adverse effects) were rarely discussed.
      Pharmacy staff rarely encouraged patients to ask questions. CONCLUSIONS: Pharmacy
      staff members provided little medication-related information at the counter,
      especially for repeat prescriptions, did not encourage active patient
      participation, and thereby did not adhere to the guidelines of their professional
      organisation. Further research is needed to understand the reasons for this.

PMID- 25988372
TI  - Changes in mortality due to major alcohol-related diseases in four Nordic
      countries, France and Germany between 1980 and 2009: a comparative age-period
      cohort analysis.
AB  - AIMS: To investigate age, period and cohort effects on time trends of alcohol
      related mortality in countries with different drinking habits and alcohol
      policies. DESIGN AND SETTING: Age-period-cohort (APC) analyses on alcohol-related
      mortality were conducted in Denmark, Finland, Norway, Sweden, France and Germany.
      PARTICIPANTS: Cases included alcohol-related deaths in the age range 20-84 years
      between 1980 and 2009. MEASUREMENTS: Mortality data were taken from national
      causes of death registries and covered the ICD codes alcoholic psychosis, alcohol
      use disorders, alcoholic liver disease and toxic effect of alcohol. FINDINGS: In
      all countries changes across age, period and cohort were found to be significant
      for both genders [effect value with confidence interval (CI) shown in Supporting
      information, Table S1]. Period effects pointed to an increase in alcohol-related
      mortality in Denmark, Finland and Germany and a slightly decreasing trend in
      Sweden, while in Norway an inverse U-shaped curve and in France a U-shaped curve
      was found. Compared with the cohorts born before 1960, the risk of alcohol
      related mortality declined substantially in cohorts born in the 1960s and later.
      Pairwise between-country comparisons revealed more statistically significant
      differences for period (P < 0.001 for all 15 comparisons by gender) than for age
      [P < 0.001 in seven (men) and four (women) of 15 comparisons] or cohort [P < 0.01
      in two (men) and three (women) of 15 comparisons]. CONCLUSIONS: Strong period
      effects suggest that temporal changes in alcohol-related mortality in Denmark,
      Finland, Norway, Sweden, France and Germany between 1980 and 2009 were related to
      secular differences affecting the whole population and that these effects
      differed across countries.

PMID- 25988373
TI  - Tunicate pregnane X receptor (PXR) orthologs: transcript characterization and
      natural variation.
AB  - Vertebrate pregnane X receptor (PXR, NR1I2), a ligand-activated nuclear receptor
      (NR), regulates expression of detoxification genes. Vertebrate PXR orthologs may
      adaptively evolve to bind deleterious/toxic xenobiotics typically encountered by
      organisms from their diet. Tunicates (phylum Chordata) are marine filter-feeders
      that form a sister clade to the Vertebrata. Genomes of two tunicate taxa, Ciona
      intestinalis and Botryllus schlosseri, encode at least two PXR orthologs
      (abbreviated VDR/PXRalpha and beta). Here we report characterization of the
      transcript structures and sequence variation of three tunicate PXR orthologs: C.
      intestinalis VDR/PXRalpha and beta, and B. schlosseri VDR/PXRalpha. The three
      predicted proteins consist of both DNA-binding (DBD) and ligand-binding (LBD)
      domains typical of NRs. The C. intestinalis VDR/PXRbeta LBD may be significantly
      larger than that of the VDR/PXRalpha orthologs. In both tunicate taxa, the mRNAs
      were characterized by high frequencies of single nucleotide polymorphisms (SNPs,
      ca. 3 SNPs/100 base pairs). The majority of SNPs were synonymous and standard
      tests (Tajima's D, dN/dS ratios) indicated strong purifying selection. However,
      one base pair frameshift allelic variants were found in the C. intestinalis
      VDR/PXRalpha and beta genes. The predicted proteins consisted of a DBD but lacked
      an LBD. The persistence of these variants may possibly reflect constitutive
      expression of detoxification genes as a selective advantage in the marine
      environment. These results provide a foundation for further investigations into
      the molecular evolution, population genetics and functioning of tunicate
      receptors involved in detection of marine bioactive compounds. 

PMID- 25988375
TI  - Perineal approach in strangulated rectal prolapse: early surgical intervention.

PMID- 25988376
TI  - Attachment and associated sexual health behaviors of heterosexual Mexican
      housewives.
AB  - Sexually transmitted infections including human immunodeficiency virus are
      international public health concerns. Heterosexual women who are in steady
      relationships have been described as a particularly vulnerable population at risk
      for sexually transmitted infections acquired from their male partners. In this
      pilot study, we describe associations identified via cross-sectional survey among
      demographic variables, attachment style, and condom use in Mexican heterosexual
      women (ages 20-44 years, n  =  50) who self-reported current steady partner
      relationships. Descriptive, bivariate, and correlation analyses were conducted.
      Secure attachment and condom use were positively correlated with education level.
      Limited sexual risk prevention knowledge and contraception use, low risk
      perception within male partner relationships and misconception about proper
      condom use were identified as sources of elevated risk for sexually transmitted
      infections via male partners. Implications of findings include sexual health
      intervention modification to include dialogue concerning the context of steady
      relationship and sexual risk among Mexican heterosexual women. 

PMID- 25988374
TI  - Mind the gap-deficits in our knowledge of aspects impacting the bioavailability
      of phytochemicals and their metabolites--a position paper focusing on carotenoids
      and polyphenols.
AB  - Various secondary plant metabolites or phytochemicals, including polyphenols and
      carotenoids, have been associated with a variety of health benefits, such as
      reduced incidence of type 2 diabetes, cardiovascular diseases, and several types
      of cancer, most likely due to their involvement in ameliorating inflammation and
      oxidative stress. However, discrepancies exist between their putative effects
      when comparing observational and intervention studies, especially when using pure
      compounds. These discrepancies may in part be explained by differences in intake
      levels and their bioavailability. Prior to exerting their bioactivity, these
      compounds must be made bioavailable, and considerable differences may arise due
      to their matrix release, changes during digestion, uptake, metabolism, and
      biodistribution, even before considering dose- and host-related factors. Though
      many insights have been gained on factors affecting secondary plant metabolite
      bioavailability, many gaps still exist in our knowledge. In this position paper,
      we highlight several major gaps in our understanding of phytochemical
      bioavailability, including effects of food processing, changes during digestion,
      involvement of cellular transporters in influx/efflux through the
      gastrointestinal epithelium, changes during colonic fermentation, and their phase
      I and phase II metabolism following absorption. 

PMID- 25988381
TI  - Tibor Ganti and Robert Rosen: Contrasting approaches to the same problem.
AB  - Of the various theories of life that appeared in the second half of the 20th
      century the chemoton of Tibor Ganti and the (M,R)-systems of Robert Rosen are
      among the most important, of which the former is rooted in chemical engineering
      and the latter is highly abstract. Despite apparent differences, in part due to
      very different ways of presenting them, these two approaches share some important
      characteristics: both are "closed to efficient causation", which means that they
      require nothing from their environment, and in particular not catalysts, apart
      from "food", or chemical species that allow for the production of energy. On the
      other hand Rosen insisted that a living organism cannot be regarded as a machine,
      whereas Ganti explicitly discussed its mechanical nature, and the enclosing
      boundary is explicitly created by the system itself in the chemoton, but is (at
      best) simply implicit in (M,R)-systems. 

PMID- 25988382
TI  - Molecular Cloning and Functional Characterization of Mannose Receptor in Zebra
      Fish (Danio rerio) during Infection with Aeromonas sobria.
AB  - Mannose receptor (MR) is a member of pattern-recognition receptors (PRRs), which
      plays a significant role in immunity responses. Much work on MR has been done in
      mammals and birds while little in fish. In this report, a MR gene (designated as
      zfMR) was cloned from zebra fish (Danio rerio), which is an attractive model for
      the studies of animal diseases. The full-length cDNA of zfMR contains 6248 bp
      encoding a putative protein of 1428 amino acids. The predicted amino acid
      sequences showed that zfMR contained a cysteine-rich domain, a single fibronectin
      type II (FN II) domain, eight C-type lectin-like domains (CTLDs), a transmembrane
      domain and a short C-terminal cytoplasmic domain, sharing highly conserved
      structures with MRs from the other species. The MR mRNA could be detected in all
      examined tissues with highest level in kidney. The temporal expression patterns
      of MR, IL-1beta and TNF-alpha mRNAs were analyzed in the liver, spleen, kidney
      and intestine post of infection with Aeromonas sobria. By immunohistochemistry
      assay, slight enhancement of MR protein was also observed in the spleen and
      intestine of the infected zebra fish. The established zebra fish-A. sobria
      infection model will be valuable for elucidating the role of MR in fish immune
      responses to infection. 

PMID- 25988383
TI  - The real culprit in systemic lupus erythematosus: abnormal epigenetic regulation.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple
      organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has
      been intensively studied but remains far from clear. B and T lymphocyte
      abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic
      materials, and various genetic and epigenetic factors are attributed to the
      development of SLE. The latest research findings point to the association between
      abnormal epigenetic regulation and SLE, which has attracted considerable interest
      worldwide. It is the purpose of this review to present and discuss the
      relationship between aberrant epigenetic regulation and SLE, including DNA
      methylation, histone modifications and microRNAs in patients with SLE, the
      possible mechanisms of immune dysfunction caused by epigenetic changes, and to
      better understand the roles of aberrant epigenetic regulation in the initiation
      and development of SLE and to provide an insight into the related therapeutic
      options in SLE. 

PMID- 25988384
TI  - Synthesis, characterization and biological evaluation of transition metal
      complexes derived from N, S bidentate ligands.
AB  - Two bidentate NS ligands were synthesized by the condensation reaction of S-2
      methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3
      methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of
      Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal
      complexes formed were expected to have a general formula of [M(NS)2] where M =
      Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis,
      molar conductivity, magnetic susceptibility and various spectroscopic techniques.
      The magnetic susceptibility measurements and spectral results supported the
      predicted coordination geometry in which the Schiff bases behaved as bidentate NS
      donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The
      molecular structures of the isomeric S2M2MBH (1) and S2M3MBH (2) were established
      by X-ray crystallography to have very similar l-shaped structures. The Schiff
      bases and their metal complexes were evaluated for their biological activities
      against estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB
      231) breast cancer cell lines. Only the Cu(II) complexes showed marked
      cytotoxicity against the cancer cell lines. Both Schiff bases and other metal
      complexes were found to be inactive. In concordance with the cytotoxicity
      studies, the DNA binding studies indicated that Cu(II) complexes have a strong
      DNA binding affinity. 

PMID- 25988386
TI  - Mitochondria-derived reactive oxygen species play an important role in
      Doxorubicin-induced platelet apoptosis.
AB  - Doxorubicin (DOX) is an effective chemotherapeutic agent; however; its use is
      limited by some side effects; such as cardiotoxicity and thrombocytopenia. DOX
      induced cardiotoxicity has been intensively investigated; however; DOX-induced
      thrombocytopenia has not been clearly elucidated. Here we show that DOX-induced
      mitochondria-mediated intrinsic apoptosis and glycoprotein (GP)Ibalpha shedding
      in platelets. DOX did not induce platelet activation; whereas; DOX obviously
      reduced adenosine diphosphate (ADP)- and thrombin-induced platelet aggregation;
      and impaired platelet adhesion on the von Willebrand factor (vWF) surface. In
      addition; we also show that DOX induced intracellular reactive oxygen species
      (ROS) production and mitochondrial ROS generation in a dose-dependent manner. The
      mitochondria-targeted ROS scavenger Mito-TEMPO blocked intracellular ROS and
      mitochondrial ROS generation. Furthermore; Mito-TEMPO reduced DOX-induced
      platelet apoptosis and GPIbalpha shedding. These data indicate that DOX induces
      platelet apoptosis; and impairs platelet function. Mitochondrial ROS play a
      pivotal role in DOX-induced platelet apoptosis and GPIbalpha shedding. Therefore;
      DOX-induced platelet apoptosis might contribute to DOX-triggered
      thrombocytopenia; and mitochondria-targeted ROS scavenger would have potential
      clinical utility in platelet-associated disorders involving mitochondrial
      oxidative damage. 

PMID- 25988388
TI  - Suppression of the proliferation of hypoxia-Induced retinal pigment epithelial
      cell by rapamycin through the /mTOR/HIF-1alpha/VEGF/ signaling.
AB  - Rapamycin, a highly specific inhibitor of mammalian target of rapamycin (mTOR),
      exhibits significant antitumor/antiangiogenic activity in human cancer cells. Its
      effect on the retinal pigment epithelial (RPE) cells was rarely investigated.
      This study assessed the proliferation of hypoxia-induced RPE and the inhibitory
      effects of rapamycin using 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay and examined the expression of hypoxia-inducible factor
      1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in RPE cells
      with or without rapamycin under normoxic and hypoxic conditions using real-time
      PCR and Western blot. We found that hypoxia increased the levels of mTOR, HIF
      1alpha, and VEGF. The suppression of HIF-1alpha and VEGF by rapamycin was
      associated with dephosphorylation of mTOR and the downstream effector ribosomal
      protein S6 kinase (P70S6K) and 4E-binding protein-1 (4E-BP1) of mTORC1. Rapamycin
      only inhibited the protein levels and did not change the mRNA expression of HIF
      1alpha. No cytotoxicity to the RPE cells by rapamycin was caused under either
      normoxia or hypoxia. Our data suggest that rapamycin suppresses hypoxia-induced
      RPE cell proliferation through a mechanism related to the targeting of mTOR/HIF
      1alpha/VEGF signaling. Rapamycin may potentially provide a safe and effective
      novel treatment for choroidal vascular disease.

PMID- 25988389
TI  - Gas molecule scattering & ion mobility measurements for organic macro-ions in He
      versus N2 environments.
AB  - A pending issue in linking ion mobility measurements to ion structures is that
      the collisional cross section (CCS, the measured structural parameter in ion
      mobility spectrometry) of an ion is strongly dependent upon the manner in which
      gas molecules effectively impinge on and are reemitted from ion surfaces (when
      modeling ions as fixed structures). To directly examine the gas molecule
      impingement and reemission processes and their influence, we measured the CCSs of
      positively charged ions of room temperature ionic liquids 1-ethyl-3
      methylimidazolium dicyanamide (EMIM-N(CN)2) and 1-ethyl-3-methylimidazolium
      tetrafluoroborate (EMIM-BF4) in N2 using a differential mobility analyzer-mass
      spectrometer (DMA-MS) and in He using a drift tube mobility spectrometer-mass
      spectrometer (DT-MS). Cluster ions, generated via electrosprays, took the form
      (AB)N(A)z, spanning up to z = 20 and with masses greater than 100 kDa. As
      confirmed by molecular dynamics simulations, at the measurement temperature (~300
      K), such cluster ions took on globular conformations in the gas phase. Based upon
      their attained charge levels, in neither He nor N2 did the ion-induced dipole
      potential significantly influence gas molecule-ion collisions. Therefore,
      differences in the CCSs measured for ions in the two different gases could be
      primarily attributed to differences in gas molecule behavior upon collision with
      ions. Overwhelmingly, by comparison of predicted CCSs with selected input
      impingement-reemission laws to measurements, we find that in N2, gas molecules
      collide with ions diffusely--they are reemitted at random angles relative to the
      gas molecule incoming angle--and inelastically. Meanwhile, in He, gas molecules
      collide specularly and elastically and are emitted from ion surfaces at
      determined angles. The results can be rationalized on the basis of the momentum
      transferred per collision; in the case of He, individual gas molecule collisions
      minimally perturb the atoms within a cluster ion (internal motion), while in the
      case of N2, individual gas molecules have sufficiently large momentum to alter
      the internal motion in organic ions.

PMID- 25988387
TI  - Serum amyloid A receptor blockade and incorporation into high-density lipoprotein
      modulates its pro-inflammatory and pro-thrombotic activities on vascular
      endothelial cells.
AB  - The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces
      expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1,
      VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages
      and endothelial cells, and induces endothelial dysfunction-a precursor to
      atherosclerosis. In this study, we determined the effect of pharmacological
      inhibition of known SAA receptors on pro-inflammatory and pro-thrombotic
      activities of SAA in human carotid artery endothelial cells (HCtAEC). HCtAEC were
      pre-treated with inhibitors of formyl peptide receptor-like-1 (FPRL-1), WRW4;
      receptor for advanced glycation-endproducts (RAGE), (endogenous secretory RAGE;
      esRAGE) and toll-like receptors-2/4 (TLR2/4) (OxPapC), before stimulation by
      added SAA. Inhibitor activity was also compared to high-density lipoprotein
      (HDL), a known inhibitor of SAA-induced effects on endothelial cells. SAA
      significantly increased gene expression of TF, NFkappaB and TNF and protein
      levels of TF and VEGF in HCtAEC. These effects were inhibited to variable extents
      by WRW4, esRAGE and OxPapC either alone or in combination, suggesting involvement
      of endothelial cell SAA receptors in pro-atherogenic gene expression. In
      contrast, HDL consistently showed the greatest inhibitory action, and often
      abrogated SAA-mediated responses. Increasing HDL levels relative to circulating
      free SAA may prevent SAA-mediated endothelial dysfunction and ameliorate
      atherogenesis. 

PMID- 25988390
TI  - Comparison of Fluoroscopy and Ultrasound Guidance for Sacroiliac Joint Injection
      in Patients with Chronic Low Back Pain.
AB  - BACKGROUND AND OBJECTIVES: Sacroiliac joint (SIJ) arthritis is a common cause of
      chronic mechanical low back pain (LBP) that is often treated with injection of
      local anesthetic and steroids. Ultrasound (US) has emerged as a viable
      alternative to fluoroscopy (FL) to guide SIJ injections; however, few studies
      have compared these modalities. In this prospective randomized, controlled trial,
      we compared both accuracy and efficacy of US and FL guidance for SIJ injections.
      METHODS: Forty patients with chronic moderate-to-severe LBP secondary to SIJ
      arthritis were randomized to receive US- or FL-guided unilateral SIJ injections.
      Primary outcomes included pain at 1 month measured by numerical rating scale
      (NRS) scores. Secondary outcomes included NRS scores at 24 hours, 72 hours, 1
      week, and 3 months after injection, physical functioning at 1 month after the
      procedure, procedure time, incidence of intra-articular and peri-articular needle
      placement, patient discomfort, overall patient satisfaction, and daily opioid
      consumption. RESULTS: There was no significant difference in NRS pain scores
      between the 2 groups at 1 month or at any other follow-up points. A significant
      reduction from baseline mean NRS scores was observed in both groups at 1 month
      after injection (US 22.7%, P = 0.025; FL 37.3%, P < 0.001). There was no
      significant difference in procedure-related variables, physical functioning,
      discomfort, opioid utilization, and patient satisfaction between the 2 groups.
      CONCLUSIONS: Ultrasound-guided SIJ injection with fluoroscopic confirmation has
      similar accuracy and efficacy to fluoroscopy alone for SIJ injections in patients
      with chronic low back pain secondary to SIJ arthritis.

PMID- 25988385
TI  - Molecular Connections between Cancer Cell Metabolism and the Tumor
      Microenvironment.
AB  - Cancer cells preferentially utilize glycolysis, instead of oxidative
      phosphorylation, for metabolism even in the presence of oxygen. This phenomenon
      of aerobic glycolysis, referred to as the "Warburg effect", commonly exists in a
      variety of tumors. Recent studies further demonstrate that both genetic factors
      such as oncogenes and tumor suppressors and microenvironmental factors such as
      spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer
      cells. Reciprocally, altered cancer cell metabolism can modulate the tumor
      microenvironment which plays important roles in cancer cell somatic evolution,
      metastasis, and therapeutic response. In this article, we review the progression
      of current understandings on the molecular interaction between cancer cell
      metabolism and the tumor microenvironment. In addition, we discuss the
      implications of these interactions in cancer therapy and chemoprevention. 

PMID- 25988391
TI  - Blastomeres aggregation as an efficient alternative for trophoblast culture from
      porcine parthenogenetic embryos.
AB  - Zona pellucida free (ZPF) oocytes were cultured after electrical activation to
      allow blastomeres aggregation and compared to ZP intact (ZPI) oocytes. In feeder
      dependent conditions, the trophoblast attachment and primary outgrowths were
      significantly higher in ZPF than in ZPI groups. In feeder-free conditions,
      trophoblast attachment and typical morphological trophoblast primary outgrowths
      were observed in ZPF group. The primary colonies derived from the ZPF embryos in
      both culture conditions were able to establish secondary and tertiary colonies
      and showed mRNA expression of CDX2, TEAD4 and KRT8 as trophoblast markers, while
      outgrowths from the ZPI embryos could not grow beyond primary colonies.

PMID- 25988393
TI  - Tug-of-war between corrugation and binding energy: revealing the formation of
      multiple moire patterns on a strongly interacting graphene-metal system.
AB  - The formation of multidomain epitaxial graphene on Rh(111) under ultra-high
      vacuum (UHV) conditions has been characterized by scanning tunnelling microscopy
      (STM) measurements and density functional theory (DFT) calculations. At variance
      with the accepted view for strongly interacting graphene-metal systems, we
      clearly demonstrate the formation of different rotational domains leading to
      multiple moire structures with a wide distribution of surface periodicities.
      Experiments reveal a correlation between the STM apparent corrugation and the
      lattice parameter of the moire unit cell, with corrugations of just 30-40 pm for
      the smallest moires. DFT calculations for a relevant selection of these moire
      patterns show much larger height differences and a non-monotonic behaviour with
      the moire size. Simulations based on non-equilibrium Green's function (NEGF)
      methods reproduce quantitatively the experimental trend and provide a detailed
      understanding of the interplay between electronic and geometric contributions in
      the STM contrast of graphene systems. Our study sheds light on the subtle energy
      balance among strain, corrugation and binding that drives the formation of the
      moire patterns in all graphene/metal systems and suggests an explanation for the
      success of an effective model only based on the lattice mismatch. Although low
      values of the strain energy are a necessary condition, it is the ability of
      graphene to corrugate in order to maximize the areas of favourable graphene-metal
      interactions that finally selects the stable configurations. 

PMID- 25988392
TI  - Wax, sex and the origin of species: Dual roles of insect cuticular hydrocarbons
      in adaptation and mating.
AB  - Evolutionary changes in traits that affect both ecological divergence and mating
      signals could lead to reproductive isolation and the formation of new species.
      Insect cuticular hydrocarbons (CHCs) are potential examples of such dual traits.
      They form a waxy layer on the cuticle of the insect to maintain water balance and
      prevent desiccation, while also acting as signaling molecules in mate recognition
      and chemical communication. Because the synthesis of these hydrocarbons in insect
      oenocytes occurs through a common biochemical pathway, natural or sexual
      selection on one role may affect the other. In this review, we explore how
      ecological divergence in insect CHCs can lead to divergence in mating signals and
      reproductive isolation. We suggest that the evolution of insect CHCs may be ripe
      models for understanding ecological speciation. 

PMID- 25988394
TI  - Comedications alter drug-induced liver injury reporting frequency: Data mining in
      the WHO VigiBaseTM.
AB  - Polypharmacy is common, and may modify mechanisms of drug-induced liver injury.
      We examined the effect of these drug-drug interactions on liver safety reports of
      four drugs highly associated with hepatotoxicity. In the WHO VigiBaseTM, liver
      event reports were examined for acetaminophen, isoniazid, valproic acid, and
      amoxicillin/clavulanic acid. Then, we evaluated the liver event reporting
      frequency of these 4 drugs in the presence of co-reported medications. Each of
      the 4 primary drugs was reported as having more than 2000 liver events, and co
      reported with more than 600 different medications. Overall, the effect of 2275 co
      reported drugs (316 drug classes) on the reporting frequency was analyzed.
      Decreased liver event reporting frequency was associated with 245 drugs/122 drug
      classes, including anti-TNFalpha, opioids, and folic acid. Increased liver event
      reporting frequency was associated with 170 drugs/82 drug classes; in particular,
      halogenated hydrocarbons, carboxamides, and bile acid sequestrants. After
      adjusting for age, gender, and other co-reported drug classes, multiple co
      reported drug classes were significantly associated with decreased/increased
      liver event reporting frequency in a drug-specific/unspecific manner. In
      conclusion, co-reported medications were associated with changes in the liver
      event reporting frequency of drugs commonly associated with hepatotoxicity,
      suggesting that comedications may modify drug hepatic safety. 

PMID- 25988396
TI  - MICCA: a complete and accurate software for taxonomic profiling of metagenomic
      data.
AB  - The introduction of high throughput sequencing technologies has triggered an
      increase of the number of studies in which the microbiota of environmental and
      human samples is characterized through the sequencing of selected marker genes.
      While experimental protocols have undergone a process of standardization that
      makes them accessible to a large community of scientist, standard and robust data
      analysis pipelines are still lacking. Here we introduce MICCA, a software
      pipeline for the processing of amplicon metagenomic datasets that efficiently
      combines quality filtering, clustering of Operational Taxonomic Units (OTUs),
      taxonomy assignment and phylogenetic tree inference. MICCA provides accurate
      results reaching a good compromise among modularity and usability. Moreover, we
      introduce a de-novo clustering algorithm specifically designed for the inference
      of Operational Taxonomic Units (OTUs). Tests on real and synthetic datasets shows
      that thanks to the optimized reads filtering process and to the new clustering
      algorithm, MICCA provides estimates of the number of OTUs and of other common
      ecological indices that are more accurate and robust than currently available
      pipelines. Analysis of public metagenomic datasets shows that the higher
      consistency of results improves our understanding of the structure of
      environmental and human associated microbial communities. MICCA is an open source
      project. 

PMID- 25988397
TI  - Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney
      Transplant Recipients With Allograft Dysfunction.
AB  - There is no literature on the use of belatacept for sensitized patients or
      regrafts in kidney transplantation. We present our initial experience in high
      immunologic risk kidney transplant recipients who were converted from tacrolimus
      to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or
      interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were
      switched from tacrolimus to belatacept at a median of 4 months posttransplant.
      Renal function improved significantly from a peak mean estimated glomerular
      filtration rate (eGFR) of 23.8 +/- 12.9 mL/min/1.73 m(2) prior to the switch to
      an eGFR of 42 +/- 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5
      months postconversion. No new rejection episodes were diagnosed despite a prior
      history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in
      5/6 patients did not show subclinical rejection. No development of donor-specific
      antibodies (DSA) was noted. In this preliminary investigation, we report improved
      kidney function without a concurrent increase in risk of rejection and DSA in six
      sensitized patients converted from tacrolimus to belatacept. Improvement in renal
      function was noted even in patients with chronic allograft fibrosis without
      evidence of acute CNI toxicity. Further studies with protocol biopsies are needed
      to ensure safety and wider applicability of this approach.

PMID- 25988398
TI  - Prevalence, antimicrobial resistance and genetic lineages of Enterococcus spp.
      from vegetable food, soil and irrigation water in farm environments in Tunisia.
AB  - BACKGROUND: The objective of this study was to determine the species, clonal
      diversity, antibiotic resistance and virulence of enterococci in different
      environments. Seventy-one samples of farm origin (34 of food vegetables, 27 of
      soil and ten of irrigation water) and 19 samples of vegetables from five markets,
      were inoculated in Slanetz-Bartley agar plates supplemented or not with
      gentamicin (SB-Gen and SB plates, respectively) for enterococci recovery.
      RESULTS: Enterococci were obtained from 72.2% of tested samples in SB media (food
      vegetables from farms, 88.2%; soil and irrigation water, 51%; food vegetables
      from markets, 84.2%), and 65 enterococcal isolates were obtained. Enterococcus
      faecium was the most prevalent species (52.3%), followed by E. hirae (35.4%), E.
      faecalis (6.15%), and E. casseliflavus (6.15%). Antibiotic resistance detected
      among these enterococci was as follows (percentage/detected gene): ciprofloxacin
      (60%), erythromycin (18.4%/erm(B)), tetracycline (15.4%/tet(M)-tet(L)), kanamycin
      (15.4%/aph(3')-III), chloramphenicol (7.7%), streptomycin (3%/ant(6)), vancomycin
      (6.15%/vanC2)), teicoplanin (0%) and ampicillin (0%). High-level gentamicin
      resistant (HLR-G) enterococci were detected in SB-Gen plates in 14 of 90 tested
      samples (15.5%), and 15 isolates were characterized: ten E. faecalis, four E.
      faecium and one E. hirae. All HLR-G enterococci carried the aac(6')-aph(2"),
      erm(B) and tet(M) genes, among other resistance genes. The HLR-G isolates showed
      high genetic diversity (ten different PFGE profiles), and were ascribed to the
      sequence types ST2, ST16, ST28 and new ST528 (in E. faecalis), and ST56, new
      ST885 and new ST886 (in E. faecium). CONCLUSION: Food vegetables in the farm or
      market settings are frequently contaminated by HLR-G enterococci, and these
      microorganisms could reach the human intestine through the food chain, if
      hygienic conditions are not followed. (c) 2015 Society of Chemical Industry.

PMID- 25988395
TI  - Exogenous interleukin-33 targets myeloid-derived suppressor cells and generates
      periphery-induced Foxp3+ regulatory T cells in skin-transplanted mice.
AB  - Interleukin-33 (IL-33) has been a focus of study because of its variety of
      functions shaping CD4(+) T-cell biology. In the present work, we evaluated the
      modulatory effect of IL-33 on suppressor cells in an in vivo transplantation
      model. C57BL/6 wild-type mice were grafted with syngeneic or allogeneic skin
      transplants and treated with exogenous IL-33 daily. After 10 days of treatment,
      we analysed draining lymph node cellularity and found in allogeneic animals an
      increment in myeloid-derived suppressor cells, which co-express MHC-II, and
      become enriched upon IL-33 treatment. In line with this observation, inducible
      nitric oxide synthase and arginase 1 expression were also increased in allogeneic
      animals upon IL-33 administration. In addition, IL-33 treatment up-regulated the
      number of Foxp3(+) regulatory T (Treg) cells in the allogeneic group,
      complementing the healthier integrity of the allografts and the increased
      allograft survival. Moreover, we demonstrate that IL-33 promotes CD4(+) T-cell
      expansion and conversion of CD4(+)  Foxp3(-) T cells into CD4(+)  Foxp3(+) Treg
      cells in the periphery. Lastly, the cytokine pattern of ex vivo-stimulated
      draining lymph nodes indicates that IL-33 dampens interferon-gamma and IL-17
      production, stimulating IL-10 secretion. Altogether, our work complements
      previous studies on the immune-modulatory activity of IL-33, showing that this
      cytokine affects myeloid-derived suppressor cells at the cell number and gene
      expression levels. More importantly, our research demonstrates for the first time
      that IL-33 allows for in vivo Foxp3(+) Treg cell conversion and favours an anti
      inflammatory or tolerogenic state by skewing cytokine production. Therefore, our
      data suggest a potential use of IL-33 to prevent allograft rejection, bringing
      new therapeutics to the transplantation field. 

PMID- 25988399
TI  - Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of
      Inhibitors of Checkpoint Kinase 1.
AB  - Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response,
      facilitating cell-cycle arrest to provide sufficient time for lesion repair. This
      leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness
      of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783),
      the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be
      a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for
      development. A campaign of analogue synthesis established SAR delineating ChK1
      and AChE activities and allowing identification of new leads with improved
      profiles. In silico docking using a model of AChE permitted rationalization of
      the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as
      selective, orally bioavailable ChK1 inhibitors offering excellent in vitro
      potency with significantly reduced AChE activity. In combination with
      gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and
      are efficacious in a mouse p53 mutant xenograft model. 

PMID- 25988400
TI  - Necrotising fasciitis by steroid-induced Sweet's syndrome: a case report.

PMID- 25988401
TI  - Marrow Adipose Tissue Quantification of the Lumbar Spine by Using Dual-Energy CT
      and Single-Voxel (1)H MR Spectroscopy: A Feasibility Study.
AB  - PURPOSE: To test the performance of dual-energy computed tomography (CT) in the
      assessment of marrow adipose tissue (MAT) content of the lumbar spine by using
      proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy as a reference
      standard and to determine the influence of MAT on the assessment of bone mineral
      density (BMD). MATERIALS AND METHODS: This study was institutional review board
      approved and complied with HIPAA guidelines. Written informed consent was
      obtained. Twelve obese osteopenic but otherwise healthy subjects (mean age +/-
      standard deviation, 43 years +/- 13) underwent 3-T (1)H MR spectroscopy of the L2
      vertebra by using a point-resolved spatially localized spectroscopy sequence
      without water suppression. The L2 vertebra was scanned with dual-energy CT (80
      and 140 kV) by using a dual-source multi-detector row CT scanner with a
      calibration phantom. Mean basis material composition relative to the phantom was
      estimated in the L2 vertebra. Volumetric BMD was measured with and without
      correction for MAT. Bland-Altman 95% limits of agreement and Pearson correlation
      coefficients were calculated. RESULTS: There was excellent agreement between (1)H
      MR spectroscopy and dual-energy CT, with a mean difference in fat fraction of 
      0.02 between the techniques, with a 95% confidence interval of -0.24, 0.20. There
      was a strong correlation between marrow fat fraction obtained with (1)H MR
      spectroscopy and that obtained with dual-energy CT (r = 0.91, P < .001). The
      presence of MAT led to underestimation of BMD, and this bias increased with
      increasing MAT content (P < .001). CONCLUSION: Dual-energy CT can be used to
      assess MAT content and BMD of the lumbar spine in a single examination and
      provides data that closely agree and correlate with (1)H MR spectroscopy data.

PMID- 25988402
TI  - Linking contemporary high resolution magnetic resonance imaging to the von
      Economo legacy: A study on the comparison of MRI cortical thickness and
      histological measurements of cortical structure.
AB  - The cerebral cortex is a distinctive part of the mammalian nervous system,
      displaying a spatial variety in cyto-, chemico-, and myelinoarchitecture. As part
      of a rich history of histological findings, pioneering anatomists von Economo and
      Koskinas provided detailed mappings on the cellular structure of the human
      cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas.
      Current day investigations into the structure of human cortex have embraced
      technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale
      thickness and organization of the cortical mantle in vivo. However, direct
      comparisons between current day MRI estimates and the quantitative measurements
      of early anatomists have been limited. Here, we report on a simple, but
      nevertheless important cross-analysis between the histological reports of von
      Economo and Koskinas on variation in thickness of the cortical mantle and MRI
      derived measurements of cortical thickness. We translated the von Economo
      cortical atlas to a subdivision of the commonly used Desikan-Killiany atlas (as
      part of the FreeSurfer Software package and a commonly used parcellation atlas in
      studies examining MRI cortical thickness). Next, values of "width of the cortical
      mantle" as provided by the measurements of von Economo and Koskinas were
      correlated to cortical thickness measurements derived from high-resolution
      anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP).
      Cross-correlation revealed a significant association between group-averaged MRI
      measurements of cortical thickness and histological recordings (r = 0.54, P <
      0.001). Further validating such a correlation, we manually segmented the von
      Economo parcellation atlas on the standardized Colin27 brain dataset and applied
      the obtained three-dimensional von Economo segmentation atlas to the T1 data of
      each of the HCP subjects. Highly consistent with our findings for the mapping to
      the Desikan-Killiany regions, cross-correlation between in vivo MRI cortical
      thickness and von Economo histology-derived values of cortical mantle width
      revealed a strong positive association (r = 0.62, P < 0.001). Linking today's
      state-of-the-art T1-weighted imaging to early histological examinations our
      findings indicate that MRI technology is a valid method for in vivo assessment of
      thickness of human cortex.

PMID- 25988403
TI  - Translation and cancer.

PMID- 25988404
TI  - Resolving the phylogeny of a speciose spider group, the family Linyphiidae
      (Araneae).
AB  - For high-level molecular phylogenies, a comprehensive sampling design is a key
      factor for not only improving inferential accuracy, but also for maximizing the
      explanatory power of the resulting phylogeny. Two standing problems in molecular
      phylogenies are the unstable placements of some deep and long branches, and the
      phylogenetic relationships shown by robust supported clades conflict with
      recognized knowledge. Empirical and theoretical studies suggest that increasing
      taxon sampling is expected to ameliorate, if not resolve, both problems; however,
      sometimes neither the current taxonomic system nor the established phylogeny can
      provide sufficient information to guide additional sampling design. We examined
      the phylogeny of the spider family Linyphiidae, and selected ingroup species
      based on epigynal morphology, which can be reconstructed in a phylogenetic
      context. Our analyses resulted in seven robustly supported clades within
      linyphiids. The placements of four deep and long branches are sensitive to
      variations in both outgroup and ingroup sampling, suggesting the possibility of
      long branch attraction artifacts. Results of ancestral state reconstruction
      indicate that successive state transformations of the epigynal plate are
      associated with early cladogenetic events in linyphiid diversification.
      Representatives of different subfamilies were mixed together within well
      supported clades and examination revealed that their defining characters, as per
      traditional taxonomy, are homoplastic. Furthermore, our results demonstrated that
      increasing taxon sampling produced a more informative framework, which in turn
      helps to study character evolution and interpret the relationships among
      linyphiid lineages. Additional defining characters are needed to revise the
      linyphiid taxonomic system based on our phylogenetic hypothesis. 

PMID- 25988405
TI  - Energy Balance 4 Kids with Play: Results from a Two-Year Cluster-Randomized
      Trial.
AB  - BACKGROUND: Identifying sustainable approaches to improving the physical activity
      (PA) and nutrition environments in schools is an important public health goal.
      This study examined the impact of Energy Balance for Kids with Play (EB4K with
      Play), a school-based intervention developed by the Academy of Nutrition and
      Dietetics Foundation and Playworks, on students' PA, dietary habits and
      knowledge, and weight status over 2 years. METHODS: This cluster-randomized,
      controlled trial took place in four intervention and two control schools over 2
      years (n=879; third- to fifth-grade students). PA (fourth and fifth grades only),
      dietary knowledge and behaviors, school policies, and BMI z-score were assessed
      at baseline (fall 2011), midpoint (spring 2012), and endpoint (fall 2012 for
      accelerometers; spring 2013 for all other outcomes). RESULTS: At endpoint, there
      were no group differences in change in PA or dietary behaviors, although BMI z
      score decreased overall by -0.07 (p=0.05). Students' dietary knowledge
      significantly increased, as did the amount of vegetables schools served. Post-hoc
      analyses stratified by grade revealed that, relative to control students, fourth
      grade intervention students reduced school-day sedentary time by 15 minutes
      (p=0.023) and third-grade intervention students reduced BMI z-score by -0.2
      (0.05; p<0.05). There were no signicifant differences for older students.
      CONCLUSIONS: EB4K with Play, which leverages the existing infrastructure of two
      national programs, increases children's dietary knowledge and may improve weight
      status and decrease sedentary behaviors among younger children. Future iterations
      should examine programming specific for different age groups.

PMID- 25988406
TI  - Salmonella enterica serotype enteritidis in French Polynesia, South Pacific, 2008
      2013.
AB  - Outbreaks of Salmonella enterica serotype Enteritidis infections associated with
      eggs occurred in French Polynesia during 2008-2013. Molecular analysis of
      isolates by using clustered regularly interspaced short palindromic repeat
      polymorphisms and multilocus variable-number tandem-repeat analysis was
      performed. This subtyping made defining the epidemic strain, finding the source,
      and decontaminating affected poultry flocks possible. 

PMID- 25988408
TI  - From Greek to Arabic: "Tom Morton" Cigar Box Label, Part I.

PMID- 25988407
TI  - Three-parameter shear wave inversion in MR elastography of incompressible
      transverse isotropic media: Application to in vivo lower leg muscles.
AB  - PURPOSE: To develop and demonstrate MR elastography (MRE) for the measurement of
      three independent viscoelastic constants of skeletal muscle according to the
      theory of linear elasticity of incompressible materials with transverse isotropy
      (TI). METHODS: Three-dimensional multifrequency MRE was applied to soleus,
      gastrocnemius, and tibialis anterior muscles in 10 healthy volunteers. The
      rotational wave fields were solved for complex-valued viscoelastic parameters
      MU12, MU13, and E3 corresponding to two shear moduli (within the planes of
      isotropy and symmetry of TI materials) and Young's modulus (along the principal
      fiber axis). RESULTS: Anisotropy was represented by the inequality MU12  < MU13 
      < 1/3E3 considering storage and loss properties of the soleus and gastrocnemius
      muscles, whereas storage shear moduli of tibialis were indistinguishable. Storage
      moduli were: 1.06 +/- 0.12, 1.33 +/- 0.10, 6.92 +/- 0.95 kPa (soleus); 0.90 +/-
      0.11, 1.30 +/- 0.15, 8.22 +/- 1.37 kPa (gastrocnemius); 1.26 +/- 0.16, 1.27 +/-
      0.11, 9.29 +/- 1.42 kPa (tibialis), for MU12, MU13, and E3, respectively. The
      muscles were different in their MU12 and E3 values, whereas MU13 was less
      sensitive to the muscle type. Leg differences were observed in the soleus and
      gastrocnemius muscles. CONCLUSION: Recovery of the full elasticity tensor in
      incompressible TI materials is feasible by three-dimensional inversion of the
      time-harmonic shear wave equation. The method is potentially useful for the
      clinical evaluation of skeletal muscle anisotropy.

PMID- 25988409
TI  - Capitol Hill Bill: "Tom Morton" Cigar Box Label, Part II.

PMID- 25988410
TI  - Identity Theft? "Tom Morton" Cigar Box Label, Part III.

PMID- 25988411
TI  - Correlation between the STOP-Bang Score and the Severity of Obstructive Sleep
      Apnea.

PMID- 25988412
TI  - In reply.

PMID- 25988413
TI  - Prehabilitation versus Rehabilitation.

PMID- 25988414
TI  - In reply.

PMID- 25988415
TI  - Effect of thoracic epidural anesthesia on the tolerance to acute normovolemic
      anemia: issues warranting comment.

PMID- 25988416
TI  - In reply.

PMID- 25988417
TI  - Inappropriate trial of cervical epidural injections.

PMID- 25988418
TI  - In reply.

PMID- 25988425
TI  - Stereoselective Synthesis of Natural and Non-natural Thomsen-nouveau Antigens and
      Hydrazide Derivatives.
AB  - A selective glycosylation strategy enabling access to all stereochemical
      combinations of tumor associated Thomsen-nouveau (Tn) antigen, D-GalNAc-O
      Ser/Thr, has been developed. The key component for selectivity is the phthalimide
      protected D- or L-amino acid acceptors which allow access to alpha- or beta
      anomers in excellent yields (72-96%) and selectivity (~100%) when appropriate C-2
      substitution is installed. The glycoamino acid intermediates were divergently
      converted to Tn-based carboxylates or to hydrazides by tandem Pd-C debenzylation
      followed by treatment with hydrazine hydrate or hydrazine hydrate treatment
      alone.

PMID- 25988426
TI  - Interdisciplinary management of an adolescent patient with significant previous
      trauma to the upper incisors.
AB  - Significant dental trauma may result in short-term and long-term clinical
      dilemmas. There are many factors to consider when formulating the relevant and
      reasonable treatment options for such patients. Interdisciplinary management has
      the potential to significantly improve both aesthetic and functional outcomes in
      challenging cases. With respect to each presented option, the patient must be
      informed of the inherent advantages and disadvantages, the appropriate treatment
      timing, duration and the costs involved, both financial and biological. 

PMID- 25988427
TI  - Xenotransplantation literature update, March-April 2015.

PMID- 25988428
TI  - Sequencing of the ART4 gene in sub-Saharan cohorts reveals ethnic differences and
      two new DO alleles: DO*B-Ile5Thr and DO*B-Trp266Arg.
AB  - BACKGROUND: Given the high heterogeneity of sub-Saharan populations especially
      between nonpygmoids and pygmoids, differences are expected during investigation
      of the DO/ART4 gene. STUDY DESIGN AND METHODS: Using genomic DNA extracted from
      blood samples collected from 77 Tswa pygmoids and 39 Teke and seven San
      nonpygmoids, DO coding regions were amplified and sequenced. A tetra-primer
      amplification refractory mutation system-polymerase chain reaction method was
      developed to specifically detect the DO*B-SH-Gln149Lys variant. Membrane
      expression of newly identified variant alleles in K562-transduced cells was
      studied by flow cytometry. RESULTS: Extensive polymorphism was confirmed in Teke
      or San nonpygmoids and Tswa pygmoids with, respectively, 12, zero, and 24 DO*A;
      54, 10, and 115 DO*B or DO*B-WL; five, zero, and 14 DO*HY; and six DO*JO alleles
      in Teke only. The DO*B-SH-Gln149Lys variant was observed as the third most
      frequent after the DO*HY and DO*JO alleles. Two novel DO*B alleles were
      identified in the San samples, that is, DO*B-Ile5Thr and DO*B-Trp266Arg. Study of
      K562-transduced cells showed that compared to the DO*B allele, DO*B-Ile5Thr was
      expressed more strongly while DO*B-Trp266Arg variant was expressed to a lesser
      extent and was not recognized by MIMA-123 monoclonal antibodies. CONCLUSION:
      Sequencing analysis showed more allelic combinations in nonpygmoids than in
      pygmoids with high frequencies of DO*HY, DO*JO, and DO*B-SH-Gln149Lys variant
      alleles. This finding underlines the importance of including DO*HY and DO*JO
      single-nucleotide polymorphisms in genotyping tests to improve transfusion
      safety. Characterization of two novel DO*B alleles highlights the value of
      testing selected ethnic groups in understanding DO allele diversity.

PMID- 25988429
TI  - Metabolic profile of 2-(2-hydroxypropanamido) benzoic acid in rats by ultra high
      performance liquid chromatography combined with Fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - An ultra high performance liquid chromatography combined with Fourier transform
      ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) method was developed
      to investigate the in vivo metabolism of 2-(2-hydroxypropanamido) benzoic acid
      (HPABA), a marine-derived anti-inflammatory drug, for the first time. Plasma,
      urine, feces and bile samples were collected from male and female rats after a
      single intragastric administration of HPABA at a dose of 100mg/kg. Besides the
      parent drug, a total of 13 metabolites (3 phase I and 10 phase II metabolites)
      were detected and tentatively identified through comparing their mass
      spectrometry profiles with those of HPABA. Results demonstrated that metabolic
      pathways of HPABA in rats included decarboxylation, hydroxylation,
      dehydrogenation, glucuronidation, glycine conjugation and N-acetyl conjugation.
      In summary, this work provided valuable information regarding the metabolism of
      HPABA in rats, which would contribute to better understanding of its safety and
      mechanism of action. 

PMID- 25988430
TI  - Liquid chromatography-tandem mass spectrometry for the quantification of
      flurbiprofen in human plasma and its application in a study of bioequivalence.
AB  - A simple, quick and accurate LC-MS/MS method for the quantification of
      flurbiprofen in human plasma with indomethacin as internal standard (IS) was
      developed and validated. Samples were treated with methanol to precipitate
      proteins, then separated on a Ultimate C18 column (5MUm, 2.1*50mm) with a
      gradient elusion process. Mobile phase A was comprised of water and formic acid,
      mobile phase B was comprised of acetonitrile and formic acid. Multi reaction
      monitoring (MRM) signals were saved on a negative ionization electrospray mass
      spectrometer. The calibration curve showed good linearity in the range of 40.00
      10000.00MUg/L (r(2)=0.998). Intra-day RE was 0.2-2.2%. Inter-day RE was 0.5-3.4%.
      The samples showed good stability under the study conditions. No significant
      matrix effect was observed. The established method was then applied to a
      bioequivalence study of a flurbiprofen axetil formulation. 

PMID- 25988431
TI  - The European Consensus Statement on sacral neuromodulation.

PMID- 25988432
TI  - Relationship between interpretation, alliance, and outcome in psychodynamic
      psychotherapy: control of therapist effects and assessment of moderator variable
      impact.
AB  - The current study examines the relationship between therapist interpretations in
      the early stages of psychodynamic psychotherapy and subsequent outcomes for 76
      outpatients. Pre-treatment characteristics of global symptomatology, personality
      pathology, insight, and level of object relations were examined as possible
      significant patient characteristics. Independent clinicians reliably rated
      therapist use of interpretations over two early treatment sessions (third and
      ninth). Patient-rated alliance was also examined as a possible psychotherapy
      process predictor of change. Therapy outcomes were measured based on patients'
      changes in global symptomatology and estimates of improvement across a broad
      range of functioning at the end of treatment. An examination of the study
      independent variables revealed significant relationships between pre-treatment
      personality disorder symptomatology with patient object relations (OR), patient
      OR with pre-treatment insight, and pre-treatment insight with use of therapist
      interpretation. Pre-treatment symptomatology and early treatment interpretations
      predicted reliable change in global symptomatology. Patients' estimates of
      improvement across a broad band of functioning were most significantly impacted
      by quality of alliance. Analysis of these outcome relationships controlled for
      therapist effects. Statistical implications of therapist effects are discussed in
      regard to this area of research and future directions for investigation are
      explored.

PMID- 25988433
TI  - Orbital Decompression for the Treatment of Spontaneous Globe Luxations.
AB  - AIMS: To describe the results of orbital decompression in patients with
      spontaneous globe luxations and to evaluate predisposing factors for this
      condition. METHODS: The clinical records of patients who underwent orbital
      decompression for the treatment of spontaneous globe luxations between 2010 and
      2013 were reviewed. Data collected were age, gender, predisposing factors,
      preoperative and postoperative exophthalmometry, duration of follow-up, presence
      of diplopia before and after surgery and intra- and postoperative complications.
      RESULTS: Seven patients underwent orbital decompression after spontaneous globe
      luxation during the study period. Six patients underwent bilateral decompression.
      Two patients underwent a three-wall decompression, four of them medial and
      lateral decompression and one patient medial decompression. The predisposing
      factors for globe luxation were Graves' orbitopathy, malar hypoplasia, high
      myopia, floppy eyelid syndrome and orbital fat hypertrophy in the context of
      obesity. After orbital decompression, none of the patients reported new globe
      luxations. No intraoperative complications were observed. None of the patients
      developed de novo diplopia. DISCUSSION: Orbital decompression is an effective
      method for the prevention of new episodes in patients with spontaneous globe
      luxations. It has good aesthetic and functional results and addresses the
      exophthalmos present in most cases.

PMID- 25988435
TI  - Genome-wide genetic diversity of rove beetle populations along a metal pollution
      gradient.
AB  - To what extent chemical contamination affects genetic diversity of wild
      populations remains an open question in ecotoxicology. Here we used a genome-wide
      approach (615 nuclear RADseq loci containing 3017 SNPs) and a mtDNA fragment
      (ATP6) to analyze the effect of long-term exposure to elevated concentrations of
      metals (Cd, Pb, Zn) on genetic diversity in rove beetle (Staphylinus
      erythropterus) populations living along a pollution gradient in Poland. In total,
      96 individuals collected from six sites at increasing distance from the source of
      pollution were analyzed. We found weak differentiation between populations
      suggesting extensive gene flow. The highest genetic diversity was observed in a
      population inhabiting the polluted site with the highest metal availability. This
      may suggest increased mutation rates, possibly in relation to elevated oxidative
      stress levels. The polluted site could also act as an ecological sink receiving
      numerous migrants from neighboring populations. Despite higher genetic diversity
      at the most polluted site, there was no correlation between the genetic diversity
      and metal pollution or other soil properties. We did not find a clear genomic
      signature of local adaptation to metal pollution. Like in some other cases of
      metal tolerance in soil invertebrates, high mobility may counteract possible
      effects of local selective forces associated with soil pollution. 

PMID- 25988434
TI  - Conductivity-based detection techniques in nanofluidic devices.
AB  - This review covers conductivity detection in fabricated nanochannels and
      nanopores. Improvements in nanoscale sensing are a direct result of advances in
      fabrication techniques, which produce devices with channels and pores with
      reproducible dimensions and in a variety of materials. Analytes of interest are
      detected by measuring changes in conductance as the analyte accumulates in the
      channel or passes transiently through the pore. These detection methods take
      advantage of phenomena enhanced at the nanoscale, such as ion current
      rectification, surface conductance, and dimensions comparable to the analytes of
      interest. The end result is the development of sensing technologies for a broad
      range of analytes, e.g., ions, small molecules, proteins, nucleic acids, and
      particles. 

PMID- 25988436
TI  - Using population demographic parameters to assess impacts of two polybrominated
      diphenyl ethers (BDE-47, BDE-209) on the rotifer Brachionus plicatilis.
AB  - Polybrominated diphenyl ethers (PBDEs) are highly persistent anthropogenic
      contaminants found in the environment, posing a risk to aquatic ecosystems,
      whereas there is a lack of data concerning their impacts on marine invertebrates.
      The objective of this study was to assess the relative lethal and sublethal
      aquatic toxicity effects of two PBDEs, BDE-47 and BDE-209 congeners, on marine
      zooplankton rotifer Brachionus plicatilis associated with PBDE concentrations and
      time of exposure. Gas chromatography-mass spectrometry (GC-MS) analyses were
      performed to determine actual PBDE concentrations. Rotifer population demographic
      parameters from life tables, including age-specific survivorship (lx), age
      specific fecundity (mx), net reproductive rate (R0), intrinsic rate of increase
      (rm), finite rate of increase (lambda), life expectancy (E0) and generation time
      (T), were used as measures of treatment effects. Results from this study have
      revealed increasingly intense negative effects on many of the rotifer demographic
      parameters with elevated PBDE concentrations. The population growth curves of B.
      plicatilis showed almost no lag phase and reached peak abundances within 11 days,
      while B. plicatilis exposed to BDE-209 had a lag phase of about 5 days. In
      addition, increased PBDE levels reduced the population abundances and peak
      population densities of B. plicatilis. The two PBDEs have caused the carrying
      capacity (K) suppressed and the negative influence turned more serious as the
      concentration rose. Results also revealed that the time to reach growth curve
      inflection point (Tp) was shortened by PBDEs to different degrees. This study not
      only indicated that life table demography and population growth curve studies
      were two important aspects used to evaluate toxicant PBDE effects, but also
      compared the two PBDE disruptions to the population growth and reproduction of
      the rotifer. 

PMID- 25988437
TI  - Underrecognized arthropod-borne and zoonotic pathogens in northern and
      northwestern Thailand: serological evidence and opportunities for awareness.
AB  - Although scrub typhus and murine typhus are well-described tropical rickettsial
      illnesses, especially in Southeast Asia, only limited evidence is available for
      rickettsia-like pathogens contributing to the burden of undifferentiated febrile
      illness. Using commercially available kits, this study measured immunoglobulin G
      (IgG) antibody seroprevalence for Coxiella burnetii, Ehrlichia chaffeensis,
      Bartonella henselae, Anaplasma phagocytophilum, and spotted fever group
      rickettsiae (SFGR) in 375 patients enrolled in undifferentiated febrile illness
      studies at Chiangrai (northern Thailand) and Mae Sot (Thai-Myanmar border).
      Ehrlichia and SFGR were the most common causes of IgG seropositivity. A distinct
      relationship between age and seropositivity was found in Chiangrai with
      acquisition of IgG titers against Ehrlichia, Bartonella, Anaplasma, and SFGR in
      young adulthood, suggesting cumulative exposure to these pathogens. At Mae Sot,
      high early IgG titers against Ehrlichia and SFGR were common, whereas Anaplasma
      and Bartonella IgG titers increased at 50-60 years. Q fever associated with low
      IgG positivity at both study sites, with significantly higher prevalence at 30
      years of age in Chiangrai. These data suggest that other rickettsial illnesses
      could contribute to the burden of febrile illness in Thailand and possibly
      adjacent regions. Improved diagnostics and better understanding of antibody
      longevity and cross-reactivity will improve identification and management of
      these easily treatable infectious diseases. 

PMID- 25988439
TI  - Evidence for West Nile virus spillover into the squirrel population in Atlanta,
      Georgia.
AB  - BACKGROUND: In the United States, spillover of West Nile virus (WNV) into wild
      mammal populations has been reported since the introduction of the virus into the
      New World in 1999. Eastern gray squirrels (Sciurus carolinensis) exhibit a high
      seroprevalence for WNV in urban settings where high virus circulation and human
      spillover have been reported. In Atlanta, Georgia, human cases of WNV are
      uncommon despite high infection rates in birds and mosquitoes. In this study, we
      evaluated WNV exposure of eastern gray squirrels in a WNV hot spot in Atlanta.
      MATERIALS AND METHODS: Gray squirrels were live-trapped in Grant Park, Atlanta,
      during July-October, 2012, and a census was conducted to estimate squirrel
      density in the study site. Sera from trapped animals were tested for circulating
      virus-by-virus isolation in cell culture and for WNV-specific antibodies by
      enzyme-linked immunosorbent assay and plaque reduction neutralization test.
      Mosquitoes were collected at the same location and tested for virus isolation.
      RESULTS: Among the 69 collected squirrels, 25 (36.2%) tested positive for WNV
      antibodies, although none were viremic. Seroprevalence was lower in juveniles
      (18.8%) than in adults (37.5%), but this difference was not statistically
      significant. Gender and squirrel density had no effect on seroprevalence.
      Seasonality of squirrel seroprevalence and of mosquito infection were
      significantly associated, both peaking in August. No difference in squirrel
      exposure was detected across the collection sites. CONCLUSIONS: We report a high
      degree of WNV exposure in squirrels in Grant Park that was correlated with
      seasonality of mosquito infection. The detection of antibodies in juveniles
      suggests that circulation of WNV in the surveyed population is ongoing. Eastern
      gray squirrels may be suitable indicators for virus amplification and for risk of
      human spillover on a local scale in urban settings.

PMID- 25988438
TI  - Single-Nucleotide Polymorphisms Reveal Spatial Diversity Among Clones of Yersinia
      pestis During Plague Outbreaks in Colorado and the Western United States.
AB  - BACKGROUND: In western North America, plague epizootics caused by Yersinia pestis
      appear to sweep across landscapes, primarily infecting and killing rodents,
      especially ground squirrels and prairie dogs. During these epizootics, the risk
      of Y. pestis transmission to humans is highest. While empirical models that
      include climatic conditions and densities of rodent hosts and fleas can predict
      when epizootics are triggered, bacterial transmission patterns across landscapes,
      and the scale at which Y. pestis is maintained in nature during inter-epizootic
      periods, are poorly defined. Elucidating the spatial extent of Y. pestis clones
      during epizootics can determine whether bacteria are propagated across landscapes
      or arise independently from local inter-epizootic maintenance reservoirs.
      MATERIAL AND METHODS: We used DNA microarray technology to identify single
      nucleotide polymorphisms (SNPs) in 34 Y. pestis isolates collected in the western
      United States from 1980 to 2006, 21 of which were collected during plague
      epizootics in Colorado. Phylogenetic comparisons were used to elucidate the
      hypothesized spread of Y. pestis between the mountainous Front Range and the
      eastern plains of northern Colorado during epizootics. Isolates collected from
      across the western United States were included for regional comparisons. RESULTS:
      By identifying SNPs that mark individual clones, our results strongly suggest
      that Y. pestis is maintained locally and that widespread epizootic activity is
      caused by multiple clones arising independently at small geographic scales. This
      is in contrast to propagation of individual clones being transported widely
      across landscapes. Regionally, our data are consistent with the notion that Y.
      pestis diversifies at relatively local scales following long-range translocation
      events. We recommend that surveillance and prediction by public health and
      wildlife management professionals focus more on models of local or regional
      weather patterns and ecological factors that may increase risk of widespread
      epizootics, rather than predicting or attempting to explain epizootics on the
      basis of movement of host species that may transport plague.

PMID- 25988440
TI  - Colorado tick fever in the United States, 2002-2012.
AB  - BACKGROUND: Colorado tick fever (CTF) is an acute systemic febrile illness caused
      by the CTF virus (CTFV). The last national summary of CTF cases in the United
      States included cases reported through 2001. This study summarizes national
      surveillance data for CTF from 2002 through 2012 and examines trends in the
      epidemiology and testing of identified CTF cases. METHODS: Because CTF is not
      nationally notifiable, we identified CTF cases through solicited reports from
      state health departments and diagnostic laboratory records. For all cases, we
      collected data on age, sex, county of residence, travel history, symptom onset
      date, laboratory testing, and clinical outcome. Poisson regression was used to
      examine trends over time in case counts, and simple linear regression and
      logistic regression were used to examine trends in case characteristics. RESULTS:
      From 2002 through 2012, 75 CTF cases were identified with a median of five cases
      per year (range 3-14). Forty-seven (63%) cases occurred in males and 49 (65%)
      occurred in people aged >=40 years. The majority (80%) of cases had onset of
      illness during May through July. Cases occurred in residents of 14 states but the
      infections were acquired in six western states. Wyoming had the highest annual
      incidence of CTF among residents (3.4 cases per million population), followed by
      Montana (1.5 per million), and Utah (0.5 per million). Over the 11 years, there
      was an increase in the proportion of cases diagnosed by RT-PCR testing and in the
      proportion of cases among travelers to another state. CONCLUSIONS: CTF cases
      continue to occur annually among residents and visitors to the western United
      States. Public health prevention messages about decreasing tick exposure should
      be targeted to residents and travelers who will spend time outdoors in an endemic
      region during the spring and summer months.

PMID- 25988441
TI  - Serologic survey of orthopoxvirus infection among rodents in hungary.
AB  - As a result of discontinuing vaccination against smallpox after the late 1970s,
      different orthopoxviruses (OPVs), such as cowpox virus (CPXV), have become a re
      emerging healthcare threat among zoonotic pathogens. In Hungary, data on OPV
      prevalence among its rodent host species have been absent. Here, rodents
      belonging to four species, i.e., striped field mouse (Apodemus agrarius), yellow
      necked mouse (A. flavicollis), wood mouse (A. sylvaticus) and bank vole (Myodes
      glareolus), were live trapped at 13 sampling plots on a 149-ha area in the Mecsek
      Mountains, Hungary, from March to September in 2011 and 2012. Rodent sera were
      collected and screened for OPV-reactive antibodies with an immunfluorescence
      assay (IFA). Among the 1587 tested rodents, 286 (18.0%) harbored OPV-specific
      antibodies. Seroprevalence was the highest for the bank vole (71.4%) and the
      striped field mouse (66.7%). Due to a masting event in the autumn of 2011 across
      Central Europe, the abundance of bank voles increased drastically in the 2012
      season, raising the overall OPV seroprevalence. We provide the first data on OPV
      occurrence and seroprevalence in rodents in Hungary. The circulation of OPV in
      rodents in densely populated areas warrants further studies to elucidate the
      zoonotic potential of OPV in humans. 

PMID- 25988442
TI  - Molecular Detection of Rickettsia africae in Amblyomma variegatum Collected from
      Sudan.
AB  - Despite the increasing awareness of the importance of emerging vector-borne
      diseases, human tick-borne diseases, particularly rickettsial infections, are
      overlooked, especially in the countries such as Sudan with limited resources to
      perform molecular-based surveys. This study aimed at detection and genetic
      characterization of Rickettsia spp. in ticks collected from Sudan. The samples
      were first screened for the presence of rickettsial agents by gltA real-time PCR
      and subsequently characterized by gltA and ompA PCR and size-based multispacer
      typing. The results demonstrated the wide distribution of Rickettsia africae
      and/or closely related species across Sudan. The results of this report highlight
      the need for careful consideration of rickettsial infections in patients with
      nonmalarial febrile illness in this country. Nationwide surveillance on ticks
      associated with human rickettsial infections in Sudan is warranted. 

PMID- 25988443
TI  - Polymicrobial Q Fever and enterococcal aortic prosthetic valve endocarditis with
      aortic root abscess.
AB  - Polymicrobial endocarditis is uncommon. We present a case of polymicrobial
      endocarditis caused by Enterococcus faecalis and Coxiella burnetii and review
      previous cases of polymicrobial endocarditis involving Coxiella burnetii. Testing
      for Q fever should be considered in any patient with endocarditis living in an
      endemic area. 

PMID- 25988445
TI  - Conversations about how we die.

PMID- 25988444
TI  - Orthobunyavirus antibodies among humans in selected parts of the Rift Valley and
      northeastern Kenya.
AB  - Ngari, Bunyamwera, Ilesha, and Germiston viruses are among the mosquito-borne
      human pathogens in the Orthobunyavirus genus, family Bunyaviridae, associated
      with febrile illness. Although the four orthobunyaviruses have been isolated from
      mosquito and/or tick vectors sampled from different geographic regions in Kenya,
      little is known of human exposure in such areas. We conducted a serologic
      investigation to determine whether orthobunyaviruses commonly infect humans in
      Kenya. Orthobunyavirus-specific antibodies were detected by plaque reduction
      neutralization tests in 89 (25.8%) of 345 persons tested. Multivariable analysis
      revealed age and residence in northeastern Kenya as risk factors. Implementation
      of acute febrile illness surveillance in northeastern Kenya will help to detect
      such infections. 

PMID- 25988448
TI  - Bird's nest and ferns: Fidelia Bridges.

PMID- 25988456
TI  - Hospital quality reporting by US News & World Report: why, how, and what's ahead.

PMID- 25988457
TI  - A piece of my mind. A silent curriculum.

PMID- 25988458
TI  - Hospital ratings: a guide for the perplexed.

PMID- 25988459
TI  - Defining amyloid pathology in persons with and without dementia syndromes: making
      the right diagnosis.

PMID- 25988460
TI  - Expression of Concern: Sato et al. Effect of folate and mecobalamin on hip
      fractures in patients with stroke: a randomized controlled trial. JAMA.
      2005;293(9):1082-1088.

PMID- 25988461
TI  - Oral steroids for acute radiculopathy due to a herniated lumbar disk: a
      randomized clinical trial.
AB  - IMPORTANCE: Oral steroids are commonly used to treat acute sciatica due to a
      herniated disk but have not been evaluated in an appropriately powered clinical
      trial. OBJECTIVE: To determine if oral prednisone is more effective than placebo
      in improving function and pain among patients with acute sciatica. DESIGN,
      SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical
      trial conducted from 2008 to 2013 in a large integrated health care delivery
      system in Northern California. Adults (n=269) with radicular pain for 3 months or
      less, an Oswestry Disability Index (ODI) score of 30 or higher (range, 0-100;
      higher scores indicate greater dysfunction), and a herniated disk confirmed by
      magnetic resonance imaging were eligible. INTERVENTIONS: Participants were
      randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral
      prednisone (5 days each of 60 mg, 40 mg, and 20 mg; total cumulative dose = 600
      mg; n = 181) or matching placebo (n = 88). MAIN OUTCOMES AND MEASURES: The
      primary outcome was ODI change at 3 weeks; secondary outcomes were ODI change at
      1 year, change in lower extremity pain (measured on a 0-10 scale; higher scores
      indicate more pain), spine surgery, and Short Form 36 Health Survey (SF-36)
      Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (0-100
      scale; higher scores better). RESULTS: Observed baseline and 3-week mean ODI
      scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the
      placebo group, respectively. The prednisone-treated group showed an adjusted mean
      6.4-point (95% CI, 1.9-10.9; P = .006) greater improvement in ODI scores at 3
      weeks than the placebo group and a mean 7.4-point (95% CI, 2.2-12.5; P = .005)
      greater improvement at 52 weeks. Compared with the placebo group, the prednisone
      group showed an adjusted mean 0.3-point (95% CI, -0.4 to 1.0; P = .34) greater
      reduction in pain at 3 weeks and a mean 0.6-point (95% CI, -0.2 to 1.3; P = .15)
      greater reduction at 52 weeks. The prednisone group showed an adjusted mean 3.3
      point (95% CI, 1.3-5.2; P = .001) greater improvement in the SF-36 PCS score at 3
      weeks, no difference in the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3
      to 5.4; P = .08), no change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI,
      -0.4 to 4.8; P = .10), and an adjusted 3.6-point (95% CI, 0.6-6.7; P = .02)
      greater improvement in the SF-36 MCS score at 52 weeks. There were no differences
      in surgery rates at 52-week follow-up. Having 1 or more adverse events at 3-week
      follow-up was more common in the prednisone group than in the placebo group
      (49.2% vs 23.9%; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with acute
      radiculopathy due to a herniated lumbar disk, a short course of oral steroids,
      compared with placebo, resulted in modestly improved function and no improvement
      in pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00668434.

PMID- 25988464
TI  - Stroke prevention in atrial fibrillation: a systematic review.
AB  - IMPORTANCE: Atrial fibrillation (AF) is associated with an increase in mortality
      and morbidity, with a substantial increase in stroke and systemic
      thromboembolism. Strokes related to AF are associated with higher mortality,
      greater disability, longer hospital stays, and lower chance of being discharged
      home than strokes unrelated to AF. OBJECTIVE: To provide an overview of current
      concepts and recent developments in stroke prevention in AF, with suggestions for
      practical management. EVIDENCE REVIEW: A comprehensive structured literature
      search was performed using MEDLINE for studies published through March 11, 2015,
      that reported on AF and stroke, bleeding risk factors, and stroke prevention.
      FINDINGS: The risk of stroke in AF is reduced by anticoagulant therapy.
      Thromboprophylaxis can be obtained with vitamin K antagonists (VKA, eg, warfarin)
      or a non-VKA oral anticoagulant (NOAC). Major guidelines emphasize the important
      role of oral anticoagulation (OAC) for effective stroke prevention in AF.
      Initially, clinicians should identify low-risk AF patients who do not require
      antithrombotic therapy (ie, CHA2DS2-VASc score, 0 for men; 1 for women).
      Subsequently, patients with at least 1 stroke risk factor (except when the only
      risk is being a woman) should be offered OAC. A patient's individual risk of
      bleeding from antithrombotic therapy should be assessed, and modifiable risk
      factors for bleeding should be addressed (blood pressure control, discontinuing
      unnecessary medications such as aspirin or nonsteroidal anti-inflammatory drugs).
      The international normalized ratio should be tightly controlled for patients
      receiving VKAs. CONCLUSIONS AND RELEVANCE: Stroke prevention is central to the
      management of AF, irrespective of a rate or rhythm control strategy. Following
      the initial focus on identifying low-risk patients, all others with 1 or more
      stroke risk factors should be offered OAC.

PMID- 25988465
TI  - Blood pressure control and cognitive performance: something to think about with
      aging.

PMID- 25988466
TI  - Antidepressant treatment for postnatal depression.
AB  - CLINICAL QUESTION: Are antidepressants associated with improved outcomes for
      postnatal depression? BOTTOM LINE: Compared with placebo, selective serotonin
      reuptake inhibitors (SSRIs) are associated with better response and remission
      rates for postnatal depression. However, few studies included women with severe
      depression or suicidal ideation. There are insufficient data to conclude whether
      antidepressants are associated with better outcomes than psychological
      interventions.

PMID- 25988463
TI  - Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis.
AB  - IMPORTANCE: Amyloid-beta positron emission tomography (PET) imaging allows in
      vivo detection of fibrillar plaques, a core neuropathological feature of
      Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid
      plaques also occur in patients with non-AD dementia. OBJECTIVE: To use individual
      participant data meta-analysis to estimate the prevalence of amyloid positivity
      on PET in a wide variety of dementia syndromes. DATA SOURCES: The MEDLINE and Web
      of Science databases were searched from January 2004 to April 2015 for amyloid
      PET studies. STUDY SELECTION: Case reports and studies on neurological or
      psychiatric diseases other than dementia were excluded. Corresponding authors of
      eligible cohorts were invited to provide individual participant data. DATA
      EXTRACTION AND SYNTHESIS: Data were provided for 1359 participants with
      clinically diagnosed AD and 538 participants with non-AD dementia. The reference
      groups were 1849 healthy control participants (based on amyloid PET) and an
      independent sample of 1369 AD participants (based on autopsy). MAIN OUTCOMES AND
      MEASURES: Estimated prevalence of positive amyloid PET scans according to
      diagnosis, age, and apolipoprotein E (APOE) epsilon4 status, using the
      generalized estimating equations method. RESULTS: The likelihood of amyloid
      positivity was associated with age and APOE epsilon4 status. In AD dementia, the
      prevalence of amyloid positivity decreased from age 50 to 90 years in APOE
      epsilon4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%]
      at 90 years; n = 377) and to a lesser degree in APOE epsilon4 carriers (97% [95%
      CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01).
      Similar associations of age and APOE epsilon4 with amyloid positivity were
      observed in participants with AD dementia at autopsy. In most non-AD dementias,
      amyloid positivity increased with both age (from 60 to 80 years) and APOE
      epsilon4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI,
      48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18],
      29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years;
      frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to
      43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at
      60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n =
      30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years;
      noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at
      80 years. CONCLUSIONS AND RELEVANCE: Among participants with dementia, the
      prevalence of amyloid positivity was associated with clinical diagnosis, age, and
      APOE genotype. These findings indicate the potential clinical utility of amyloid
      imaging for differential diagnosis in early-onset dementia and to support the
      clinical diagnosis of participants with AD dementia and noncarrier APOE epsilon4
      status who are older than 70 years.

PMID- 25988467
TI  - Iris heterochromia and unilateral eyelash hypertrichosis.

PMID- 25988468
TI  - Prevalence of the metabolic syndrome in the United States, 2003-2012.

PMID- 25988462
TI  - Prevalence of cerebral amyloid pathology in persons without dementia: a meta
      analysis.
AB  - IMPORTANCE: Cerebral amyloid-beta aggregation is an early pathological event in
      Alzheimer disease (AD), starting decades before dementia onset. Estimates of the
      prevalence of amyloid pathology in persons without dementia are needed to
      understand the development of AD and to design prevention studies. OBJECTIVE: To
      use individual participant data meta-analysis to estimate the prevalence of
      amyloid pathology as measured with biomarkers in participants with normal
      cognition, subjective cognitive impairment (SCI), or mild cognitive impairment
      (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies
      published before April 2015 using the MEDLINE and Web of Science databases and
      through personal communication with investigators. STUDY SELECTION: Studies were
      included if they provided individual participant data for participants without
      dementia and used an a priori defined cutoff for amyloid positivity. DATA
      EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants
      with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from
      55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on
      positron emission tomography or in cerebrospinal fluid according to AD risk
      factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by
      generalized estimating equations. RESULTS: The prevalence of amyloid pathology
      increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%
      51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43%
      (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71%
      (95% CI, 66%-76%) among patients with MCI. APOE-epsilon4 carriers had 2 to 3
      times higher prevalence estimates than noncarriers. The age at which 15% of the
      participants with normal cognition were amyloid positive was approximately 40
      years for APOE epsilon4epsilon4 carriers, 50 years for epsilon2epsilon4 carriers,
      55 years for epsilon3epsilon4 carriers, 65 years for epsilon3epsilon3 carriers,
      and 95 years for epsilon2epsilon3 carriers. Amyloid positivity was more common in
      highly educated participants but not associated with sex or biomarker modality.
      CONCLUSIONS AND RELEVANCE: Among persons without dementia, the prevalence of
      cerebral amyloid pathology as determined by positron emission tomography or
      cerebrospinal fluid findings was associated with age, APOE genotype, and presence
      of cognitive impairment. These findings suggest a 20- to 30-year interval between
      first development of amyloid positivity and onset of dementia.

PMID- 25988469
TI  - Treatment for Clostridium difficile infection in adults.

PMID- 25988470
TI  - Treatment for Clostridium difficile infection in adults.

PMID- 25988471
TI  - Government regulations on physician self-referral.

PMID- 25988472
TI  - Treatment for Clostridium difficile infection in adults--reply.

PMID- 25988473
TI  - Government regulations on physician self-referral.

PMID- 25988474
TI  - Government regulations on physician self-referral--reply.

PMID- 25988476
TI  - The humors: some psychological aspects of Shakespeare's tragedies.

PMID- 25988477
TI  - JAMA patient page. Childhood vaccines.

PMID- 25988478
TI  - High-throughput micro-scale cultivations and chromatography modeling: Powerful
      tools for integrated process development.
AB  - Upstream processes are rather complex to design and the productivity of cells
      under suitable cultivation conditions is hard to predict. The method of choice
      for examining the design space is to execute high-throughput cultivation
      screenings in micro-scale format. Various predictive in silico models have been
      developed for many downstream processes, leading to a reduction of time and
      material costs. This paper presents a combined optimization approach based on
      high-throughput micro-scale cultivation experiments and chromatography modeling.
      The overall optimized system must not necessarily be the one with highest product
      titers, but the one resulting in an overall superior process performance in up-
      and downstream. The methodology is presented in a case study for the Cherry
      tagged enzyme Glutathione-S-Transferase from Escherichia coli SE1. The Cherry
      TagTM (Delphi Genetics, Belgium) which can be fused to any target protein allows
      for direct product analytics by simple VIS absorption measurements. High
      throughput cultivations were carried out in a 48-well format in a BioLector micro
      scale cultivation system (m2p-Labs, Germany). The downstream process optimization
      for a set of randomly picked upstream conditions producing high yields was
      performed in silico using a chromatography modeling software developed in-house
      (ChromX). The suggested in silico-optimized operational modes for product
      capturing were validated subsequently. The overall best system was chosen based
      on a combination of excellent up- and downstream performance.

PMID- 25988479
TI  - Mycobacterium bovis in Panama, 2013.
AB  - Panama remains free of zoonotic tuberculosis caused by Mycobacterium bovis.
      However, DNA fingerprinting of 7 M. bovis isolates from a 2013 bovine
      tuberculosis outbreak indicated minimal homology with strains previously
      circulating in Panama. M. bovis dispersion into Panama highlights the need for
      enhanced genotype testing to track zoonotic infections. 

PMID- 25988480
TI  - Reply: To PMID 25512203.

PMID- 25988482
TI  - Reply: To PMID 25988345.

PMID- 25988481
TI  - Influence of soil properties and soil leaching on the toxicity of ionic silver to
      plants.
AB  - Silver (Ag) has been shown to exhibit antimicrobial properties; as a result, it
      is being used increasingly in a wide range of consumer products. With these uses,
      the likelihood that Ag may enter the environment has increased, predominately via
      land application of biosolids or irrigation with treated wastewater effluent. The
      aim of the present study was to investigate the toxicity of Ag to 2 plant
      species: barley (Hordeum vulgare L. CV Triumph) and tomato (Lycopersicum
      esculentum) in a range of soils under both leached and unleached conditions. The
      concentrations that resulted in a 50% reduction of plant growth (EC50) were found
      to vary up to 20-fold across the soils, indicating a large influence of soil type
      on Ag toxicity. Overall, barley root elongation was found to be the least
      sensitive to added Ag, with EC50 values ranging from 51 mg/kg to 1030 mg/kg,
      whereas the tomato plant height showed higher sensitivity with EC50 values
      ranging from 46 mg/kg to 486 mg/kg. The effect of leaching was more evident in
      the barley toxicity results, where higher concentrations of Ag were required to
      induce toxicity. Variations in soil organic carbon and pH were found to be
      primarily responsible for mitigating Ag toxicity; therefore, these properties may
      be used in future risk assessments for Ag to predict toxicity in a wide range of
      soil types.

PMID- 25988483
TI  - Picky eating and child weight status development: a longitudinal study.
AB  - BACKGROUND: Children's picky eating behaviour has been linked both to being
      overweight and underweight. However, the role of parenting practices in this
      relationship has rarely been investigated. The present study aimed to clarify the
      direction of the association between picky eating and weight status and to
      examine the moderating role of food parenting practices. METHODS: The present
      study comprised a longitudinal study on the effects of picky eating on child
      weight status within the KOALA Birth Cohort Study, the Netherlands. Mothers and
      their children were included in the analyses. Children's picky eating behaviour
      and food parenting practices were assessed at baseline (child age 5 years). Their
      weight status was assessed repeatedly until age 9 years. Mixed effects linear and
      logistic regressions were used to compare picky eaters (n = 403) and non-picky
      eaters (n = 621) on changes in weight status over the years. RESULTS: At baseline
      of age 5 years, picky eaters were slightly shorter, more often underweight and
      less often overweight than non-picky eaters, whereas energy intake in relation to
      body weight (kJ kg(-1)) was similar. Picky eaters with a normal weight at
      baseline had no increased risk of becoming underweight during follow-up until age
      9 years, and were less likely to become overweight compared to non-picky eaters.
      There were no interactions with food parenting practices. The parents of picky
      eaters more often reported pressuring their child to eat and restrict unhealthy
      food intake compared to parents of non-picky eaters. CONCLUSIONS: The association
      between picky eating and child weight status was not influenced by parenting
      practices.

PMID- 25988484
TI  - Carnobacterium divergens Bacteremia in woman.

PMID- 25988485
TI  - Relationship between Quantified Instrumental Swallowing Examination and
      Comprehensive Clinical Swallowing Examination.
AB  - The aim of this study was to identify the correlation between the Mann Assessment
      of Swallowing Ability (MASA) and the Videofluoroscopic Dysphagia Scale (VDS) to
      investigate the applicability of the MASA as a follow-up test of swallowing
      function. Criterion validity was assessed for MASA results versus VDS scores of
      tests administered to 54 patients who had a stroke and dysphagia. A significant
      correlation was found between the MASA and the VDS (correlation coefficient = 
      0.509). In analyses of test-re-test reliability and inter-rater reliability of
      the scoring scale, intraclass correlation coefficients (2, 1) were high (0.98,
      0.99). In conclusion, the results of the present study indicate that the MASA
      holds adequate clinical test-re-test and inter-rater reliabilities and criterion
      validity for measuring the swallowing abilities of Korean patients who had a
      stroke and dysphagia. The MASA could contribute to more systematic management of
      swallowing problems and efficient therapeutic service.

PMID- 25988486
TI  - Vibrational and Rotational Mode Specificity in The Cl + H2O -> HCl + OH Reaction:
      A Quantum Dynamical Study.
AB  - The vibrational and rotational mode specificity of the Cl + H2O -> HCl + OH
      reaction is studied on a recently constructed ab initio based global potential
      energy surface using an initial state selected Chebyshev real wave packet method.
      The full-dimensional quantum dynamical results under the centrifugal sudden
      and/or J-shifting approximations indicate that this reaction is enhanced strongly
      by excitations of the stretching modes of the H2O reactant but only weakly by
      bending excitations. On the other hand, combination modes are found to enhance
      the reaction more than the sum of individual excitations. In addition, rotational
      excitation of the H2O reactant slightly inhibits the reactivity. The observed
      mode specificity is consistent with the predictions of the recently proposed
      Sudden Vector Projection model, which attributes the promotional effects of the
      reactant modes to their couplings with the reaction coordinate at the transition
      state. 

PMID- 25988487
TI  - Synthesis and characterization of brush-like multigraft copolymers PnBA-g-PMMA by
      a combination of emulsion AGET ATRP and emulsion polymerization.
AB  - In this paper, poly(n-butyl acrylate)-g-poly(methyl methacrylate) multigraft
      copolymers were synthesized by macromonomer technique and miniemulsion
      copolymerization. The PMMA macromonomers were obtained by an activator generated
      by electron transfer atom transfer radical polymerization (AGET ATRP) in emulsion
      system and subsequent allylation. Then the copolymerization of different
      macromonomers with nBA was carried out in miniemulsion system, obtaining
      multigraft copolymers with high molecular weight. The latex particles and
      distribution of emulsion AGET ATRP and miniemulsion copolymerization were
      characterized using laser light scattering. The molecular weight and
      polydispersity indices of macromonomers and multigraft copolymers were analyzed
      by gel permeation chromatography, and the number-average molecular weight range
      is 187,600-554,800 g/mol for PnBA-g-PMMA copolymers. In addition, the structural
      characteristics of macromonomer and brush-like copolymers were determined by
      infrared spectra and (1)H nuclear magnetic resonance spectroscopy. The thermal
      performance of brush-like copolymers were characterized by differential scanning
      calorimetry and thermogravimetric analysis. Atomic force microscopy results
      showed that the degree of microphase separation was varying with increasing PMMA
      content in PnBA-g-PMMA. The dynamic rheometer analysis revealed that multigraft
      copolymer with PMMA content of 31.4% exhibited good elastomeric properties to
      function as a TPE. These multigraft copolymers show a promising low cost and
      environmental friendly thermoplastic elastomer.

PMID- 25988488
TI  - Natrolite zeolite supported copper nanoparticles as an efficient heterogeneous
      catalyst for the 1,3-diploar cycloaddition and cyanation of aryl iodides under
      ligand-free conditions.
AB  - In this paper, we report the preparation of Natrolite zeolite supported copper
      nanoparticles as a heterogeneous catalyst for 1,3-diploar cycloaddition and
      synthesis aryl nitriles from aryl iodides under ligand-free conditions. The
      catalyst was characterized using XRD, SEM, TEM, EDS and TG-DTA. The experimental
      procedure is simple, the products are formed in high yields and the catalyst can
      be recycled and reused several times without any significant loss of catalytic
      activity. 

PMID- 25988489
TI  - Joint tumor growth prediction and tumor segmentation on therapeutic follow-up PET
      images.
AB  - Tumor response to treatment varies among patients. Patient-specific prediction of
      tumor evolution based on medical images during the treatment can help to build
      and adapt patient's treatment planning in a non-invasive way. Personalized tumor
      growth modeling allows patient-specific prediction by estimating model parameters
      based on individual's images. The model parameters are often estimated by
      optimizing a cost function constructed based on the tumor delineations. In this
      paper, we propose a joint framework for tumor growth prediction and tumor
      segmentation in the context of patient's therapeutic follow ups. Throughout the
      treatment, a series of sequential positron emission tomography (PET) images are
      acquired for tumor response monitoring. We propose to take into account the
      predicted information, which is used in combination with the random walks (RW)
      algorithm, to develop an automatic tumor segmentation method on PET images.
      Moreover, we propose an iterative scheme of RW, making the segmentation more
      performant. Furthermore, the obtained segmentation is applied to the process of
      model parameter estimation so as to get the model based prediction of tumor
      evolution. We evaluate our methods on 7 lung tumor patients, totaling 29 PET
      exams, under radiotherapy by comparing the obtained tumor prediction and tumor
      segmentation with manual tumor delineation by expert. Our system produces
      promising results when compared to the state-of-the-art methods. 

PMID- 25988490
TI  - Discriminative dictionary learning for abdominal multi-organ segmentation.
AB  - An automated segmentation method is presented for multi-organ segmentation in
      abdominal CT images. Dictionary learning and sparse coding techniques are used in
      the proposed method to generate target specific priors for segmentation. The
      method simultaneously learns dictionaries which have reconstructive power and
      classifiers which have discriminative ability from a set of selected atlases.
      Based on the learnt dictionaries and classifiers, probabilistic atlases are then
      generated to provide priors for the segmentation of unseen target images. The
      final segmentation is obtained by applying a post-processing step based on a
      graph-cuts method. In addition, this paper proposes a voxel-wise local atlas
      selection strategy to deal with high inter-subject variation in abdominal CT
      images. The segmentation performance of the proposed method with different atlas
      selection strategies are also compared. Our proposed method has been evaluated on
      a database of 150 abdominal CT images and achieves a promising segmentation
      performance with Dice overlap values of 94.9%, 93.6%, 71.1%, and 92.5% for liver,
      kidneys, pancreas, and spleen, respectively. 

PMID- 25988492
TI  - Spin-driven symmetry breaking in the frustrated fcc pyrite MnS2.
AB  - We report the characterisation of natural samples of the cubic pyrite mineral
      MnS2 using very high resolution synchrotron x-ray diffraction techniques. At low
      temperatures we find a new low temperature polymorph, which results from coupling
      between magnetic and lattice degrees of freedom. Below the magnetic ordering
      temperature T(N) = 48 K, we detect a pseudo-tetragonal distortion with a tiny c/a
      ratio of 1.0006. The structure can be refined in the space group Pbca The
      symmetry lowering reduces magnetic frustration in the fcc Mn(2+) lattice and is
      likely responsible for the previously reported lock-in of the magnetic
      propagation vector. This behaviour is similar to the spin-Peierls phase
      transitions reported in other three-dimensional Heisenberg magnets like the
      chromate spinels.

PMID- 25988491
TI  - The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic
      Preconditioning.
AB  - The endogenous electric field (EF)-directed migration of keratinocytes
      (galvanotaxis) into wounds is an essential step in wound re-epithelialization.
      Hypoxia, which occurs immediately after injury, acts as an early stimulus to
      initiate the healing process; however, the mechanisms for this effect, remain
      elusive. We show here that the galvanotactic migration of keratinocytes was
      enhanced by hypoxia preconditioning as a result of the increased directionality
      rather than the increased motility of keratinocytes. This enhancement was both
      oxygen tension- and preconditioning time-dependent, with the maximum effects
      achieved using 2% O2 preconditioning for 6 hours. Hypoxic preconditioning (2% O2,
      6 hours) decreased the threshold voltage of galvanotaxis to < 25 mV/mm, whereas
      this value was between 25 and 50 mV/mm in the normal culture control. In a
      scratch-wound monolayer assay in which the applied EF was in the default healing
      direction, hypoxic preconditioning accelerated healing by 1.38-fold compared with
      the control conditions. Scavenging of the induced ROS by N-acetylcysteine (NAC)
      abolished the enhanced galvanotaxis and the accelerated healing by hypoxic
      preconditioning. Our data demonstrate a novel and unsuspected role of hypoxia in
      supporting keratinocyte galvanotaxis. Enhancing the galvanotactic response of
      cells might therefore be a clinically attractive approach to induce improved
      wound healing. 

PMID- 25988493
TI  - Combretastatin A4-phosphate and its potential in veterinary oncology: a review.
AB  - For many years, research on anticancer therapy has focussed almost exclusively on
      targeting cancer cells directly, to selectively kill them or restrict their
      growth. But limited advances in this strategy have led researchers to shift their
      attention to other potential targets. Active research is now on-going on
      targeting tumour stroma. Vascular disrupting agents (VDAs) appear a promising
      class of anticancer drugs that are currently under investigation as a sole or
      combined therapy in human cancer patients. This article will briefly touch on the
      history and biology of combretastatin A4-phosphate (CA4P) as a typical example of
      VDAs and will concentrate on the side effects that can be expected when used in
      veterinary patients. Particularly, the pathogenesis of these side effects and how
      they may be prevented and/or treated will be discussed. The purpose of this
      article is to illustrate the potentials of CA4P as anticancer therapy in
      veterinary oncology patients.

PMID- 25988494
TI  - Glycoprotein labeling with click chemistry (GLCC) and carbohydrate detection.
AB  - Molecular labeling and detection techniques are essential to research in life
      science. Here, a method for glycoprotein labeling/carbohydrate detection through
      glycan replacement, termed glycoprotein labeling with click chemistry (GLCC), is
      described. In this method, a glycoprotein is first treated with specific
      glycosidases to remove certain sugar residues, a procedure that creates acceptor
      sites for a specific glycosyltransferase. A 'clickable' monosaccharide is then
      installed onto these sites by the glycosyltransferase. This modified glycoprotein
      is then conjugated to a reporter molecule using a click chemistry reaction. For
      glycoproteins that already contain vacant glycosylation sites, deglycosylation is
      not needed before the labeling step. As a demonstration, labeling on fetal bovine
      fetuin, mouse immunoglobulin IgG and bacterial expressed human TNFalpha and
      TNFbeta are shown. Compared to traditional ways of protein labeling, labeling at
      glycosylation sites with GLCC is considerably more specific and less likely to
      have adverse effects, and, when utilized as a method for carbohydrate detection,
      this method is also highly specific and sensitive. 

PMID- 25988495
TI  - Synthesis, characterization and in vitro evaluation of a series of novel
      polyrotaxane-based delivery system for artesunate.
AB  - A series of novel artesunate-polyrotaxanes (ATS-PRs) with folic acid capped, in
      which artesunate (ATS) was covalently bound to a cyclodextrin (CD) of the
      polyrotaxane (PR), were synthesized and were characterized by NMR, XRD, TG and
      DSC. The cytotoxicities of ATS-PRs on human colon cancer cell lines HT-29, SW480,
      HTC116 and DLD-1 showed that their antitumor activities were better than that of
      artesunate (ATS) and dihydroartemisinin (DHA). These ATS-PRs may provide a useful
      approach to the development of a highly effective drug candidate for the
      chemotherapy of human colon cancer. 

PMID- 25988496
TI  - Structure of the O-polysaccharide of Escherichia coli O87.
AB  - The following structure of the O-polysaccharide of Escherichia coli HS1/2 serving
      as a primary receptor for bacteriophage DT57-12 was elucidated by sugar analysis
      along with 1D and 2D (1)H and (13)C NMR spectroscopy: This structure is shared by
      E. coli O87 type strain. Putatively assigned functions of genes in the O-antigen
      gene cluster of E. coli O87 are consistent with the O-polysaccharide structure
      established. 

PMID- 25988497
TI  - 38th annual scientific meeting of the research society on alcoholism, june 20-24 
      san antonio, Texas.

PMID- 25988498
TI  - Green Color Purification in Tb(3+) Ions through Silica Inverse Opal
      Heterostructure.
AB  - The ordered SiO2:Tb(3+) inverse opal heterostructure films are fabricated through
      polystyrene spheres hetero-opal template using the convective self-assembly
      method to examine their potential for color purification. Their optical
      properties and photoluminescence have been investigated and compared with
      individual single inverse opals and reference (SiO2:Tb(3+) powder). The
      heterostructures are shown to possess two broad photonic stop bands separated by
      an effective pass band, causing suppression of blue, orange, and red emission
      bands corresponding to (5)D4 -> (7)F(j); j = 6, 4, 3 transitions, respectively
      and an enhancement of green emission (i.e., (5)D4 -> (7)F5). Although the
      suppression of various emission occurs because of its overlap with the photonic
      band gaps (PSBs), the enhancement of green radiation is observed because of its
      location matching with the pass band region. The Commission International de
      l'Eclairage (CIE) chromaticity coordinates of the emission spectrum of the
      heterostructure based on polystyrene sphere of 390 and 500 nm diameter are x =
      0.2936, y = 0.6512 and lie closest to those of standard green color (wavelength
      545 nm). In addition, a significant increase observed in luminescence lifetime
      for (5)D4 level of terbium in inverse opal heterostructures vis-a-vis reference
      (SiO2:Tb(3+) powder) is attributed to the change in the effective refractive
      index.

PMID- 25988499
TI  - High Molybdenum availability for evolution in a Mesoproterozoic lacustrine
      environment.
AB  - Trace metal data for Proterozoic marine euxinic sediments imply that the
      expansion of nitrogen-fixing cyanobacteria and diversification of eukaryotes were
      delayed while the availability of bioessential metals such as molybdenum in the
      ocean was limited. However, there is increasing recognition that the
      Mesoproterozoic evolution of nitrogen fixation and eukaryotic life may have been
      promoted in marginal marine and terrestrial environments, including lakes, rather
      than in the deep ocean. Molybdenum availability is critical to life in lakes,
      just as it is in the oceans. It is, therefore, important to assess molybdenum
      availability to the lacustrine environment in the Mesoproterozoic. Here we show
      that the flux of molybdenum to a Mesoproterozoic lake was 1 to 2 orders of
      magnitude greater than typical fluxes in the modern and ancient marine
      environment. Thus, there was no barrier to availability to prevent evolution in
      the terrestrial environment, in contrast to the nutrient-limited Mesoproterozoic
      oceans. 

PMID- 25988500
TI  - Competition between Fibrillation and Induction of Vesicle Fusion for the Membrane
      Associated 40-Residue beta-Amyloid Peptides.
AB  - Disruption of the cell membrane by the beta-amyloid (Abeta) peptides has been
      considered as a main mechanism of Alzheimer's disease. The peptide-to-lipid molar
      ratio (P:L) varies over a broad range biologically. We report here that two of
      the previously observed Abeta evolution pathways, fibrillation and induction of
      vesicle fusion, compete with each other when P:L varies in model Abeta-liposome
      systems. Fibrillation is preferred at higher P:L values, and fusion is promoted
      at lower P:L values. Structural studies suggest that the same residues in Abeta
      may involve in both the initial fibrillation and membrane binding at the fusion
      sites. 

PMID- 25988501
TI  - Multiplexed Millimeter Wave Communication with Dual Orbital Angular Momentum
      (OAM) Mode Antennas.
AB  - Communications using the orbital angular momentum (OAM) of radio waves have
      attracted much attention in recent years. In this paper, a novel millimeter-wave
      dual OAM mode antenna is cleverly designed, using which a 60 GHz wireless
      communication link with two separate OAM channels is experimentally demonstrated.
      The main body of the dual OAM antenna is a traveling-wave ring resonator using
      two feeding ports fed by a 90 degrees  hybrid coupler. A parabolic reflector is
      used to focus the beams. All the antenna components are fabricated by 3D printing
      technique and the electro-less copper plating surface treatment process. The
      performances of the antenna, such as S-parameters, near-fields, directivity, and
      isolation between the two OAM modes are measured. Experimental results show that
      this antenna can radiate two coaxially propagating OAM modes beams
      simultaneously. The multiplexing and de-multiplexing are easily realized in the
      antennas themselves. The two OAM mode channels have good isolation of more than
      20 dB, thus ensuring the reliable transmission links at the same time. 

PMID- 25988502
TI  - NK cell immunophenotypic and genotypic analysis of infants with severe
      respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the leading cause of severe lower
      respiratory tract infection in infants. Reduced numbers of NK cells have been
      reported in infants with severe RSV infection; however, the precise role of NK
      cells during acute RSV infection is unclear. In this study the NK and T cell
      phenotypes, LILRB1 gene polymorphisms and KIR genotypes of infants hospitalized
      with RSV infection were analyzed. Compared to controls, infants with acute RSV
      infection showed a higher proportion of LILRB1+ T cells; in addition, a subgroup
      of infants with RSV infection showed an increase in LILRB1+ NK cells. No
      differences in NKG2C, NKG2A, or CD161 expression between RSV infected infants and
      controls were observed. LILRB1 genotype distribution of the rs3760860 A>G, and
      rs3760861 A>G single nucleotide polymorphisms differed between infants with RSV
      infection and healthy donors, whereas no differences in any of the KIR genes were
      observed. Our results suggest that LILRB1 participates in the pathogenesis of RSV
      infection. Further studies are needed to define the role of LILRB1+ NK in
      response to RSV and to confirm an association between LILRB1 polymorphisms and
      the risk of severe RSV infection. 

PMID- 25988503
TI  - Sex differences in obesity incidence: 20-year prospective cohort in South Africa.
AB  - BACKGROUND: Prospective data spanning childhood and adolescence are needed to
      better understand obesity incidence among children and to identify important
      periods for intervention. OBJECTIVE: To describe gender differences in overweight
      and obesity from infancy to late adolescence in a South African cohort. METHODS:
      We analysed body mass index at 1-2 years, 4-8 years, 11-12 years, 13-15 years and
      16-18 years among 1172 participants in the South African Birth-to-Twenty cohort.
      RESULTS: Among boys, overweight and obesity prevalence declined from age 1-2
      years to 16-18 years. Among girls, overweight and obesity prevalence increased
      from 4-8 years to 16-18 years. Obesity incidence was highest from 4-8 years to 11
      12 years in boys (6.8 cases per 1000 person-years) and from 11-12 years to 13-15
      years in girls (11.2 cases per 1000 person-years). Among girls, obesity at 16-18
      years was associated with overweight (odds ratio [OR] = 3.6; 95% confidence
      interval [CI] 1.8-7.2) or obesity (OR = 8.0; 95% CI 3.7-17.6) at 1-2 years and
      overweight (OR = 6.8; 95% CI 3.3-13.9) or obesity (OR = 42.3; 95% CI 15.0-118.8)
      at 4-8 years; for boys, obesity at 16-18 years was associated with overweight at
      1-2 years (OR = 5.6; 95% CI 1.7-18.0) and obesity at 4-8 years (OR = 19.7; 95% CI
      5.1-75.9). CONCLUSIONS: Among girls, overweight and obesity increased throughout
      childhood. Overweight and obesity were not widely prevalent among boys. Early
      childhood and post-puberty may be important periods for intervention among girls.

PMID- 25988504
TI  - The concept of geodesic curvature applied to optical surfaces.
AB  - PURPOSE: To propose geodesic curvature as a metric to characterise how an optical
      surface locally differs from axial symmetry. To derive equations to evaluate
      geodesic curvatures of arbitrary surfaces expressed in polar coordinates.
      METHODS: The concept of geodesic curvature is explained in detail as compared to
      other curvature-based metrics. Starting with the formula representing a surface
      as function of polar coordinates, an equation for the geodesic curvature is
      obtained depending only on first and second radial and first order angular
      derivatives of the surface function. The potential of the geodesic curvature is
      illustrated using different surface tests. RESULTS: Geodesic curvature reveals
      local axial asymmetries more sharply than other types of curvatures such as
      normal curvatures. CONCLUSION: Geodesic curvature maps could be used to
      characterise local axial asymmetries for relevant optometry applications such as
      corneal topography anomalies (keratoconus) or ophthalmic lens metrology.

PMID- 25988505
TI  - Distress, race/ethnicity and smoking cessation in treatment-seekers: implications
      for disparity elimination.
AB  - BACKGROUND AND AIMS: Distress is a modifiable risk factor for smoking
      maintenance. This study aimed to assess racial/ethnic differences in distress pre
      and post-cognitive-behavioral therapy (CBT) for smoking cessation, and relations
      with abstinence. DESIGN: Analyses of variance and logistic regressions were
      conducted. SETTING: University-based smoking cessation laboratory in South
      Florida, USA. PARTICIPANTS: The sample comprised 234 treatment-seekers recruited
      from the community (18% white, 60% African American and 22% Hispanic).
      INTERVENTION: All participants received eight sessions of group CBT plus 8 weeks
      of transdermal nicotine patches (TNP). MEASUREMENTS: Demographics and smoking
      history [baseline], perceived stress and depressive symptoms [baseline and end of
      therapy (EOT)], carbon monoxide-verified 7-day point prevalence abstinence
      (p.p.a.) at EOT, 3 months post-CBT (primary outcome) and 6 months (self-report).
      FINDINGS: Compared with whites, African Americans reported greater baseline
      perceived stress (P = 0.03) and depressive symptoms (P = 0.06); no EOT
      differences were found. African Americans (P < 0.001) and Hispanics (P < 0.01)
      reported greater perceived stress reduction, and African Americans reported
      greater reductions in depressive symptoms (P < 0.01). EOT-perceived stress
      (adjusted odds ratio (AOR) = 0.93 (0.89-0.98)) and depressive symptoms [AOR =
      0.96 (0.93-0.99)] were associated inversely with 7-day p.p.a. at 3 months.
      Reductions in perceived stress [AOR = 0.93 (0.89-0.98)] and depressive symptoms
      at the EOT [AOR = 0.96 (0.93-0.99)] were associated with cessation, such that
      reduced distress increased the odds of abstinence. The interactions between
      race/ethnicity and distress on 7-day p.p.a. were not significant at any
      assessment point. CONCLUSIONS: Among smokers in Florida, USA, racial/ethnic
      differences in distress before starting cognitive-behavioral therapy for smoking
      cessation were eliminated at the end of treatment, driven by improvements among
      African Americans and Hispanics. High levels of distress were associated with
      reduced odds of abstinence through 6 months across racial/ethnic groups.

PMID- 25988506
TI  - 'Everything's fine, so why does it happen?' A qualitative investigation of
      patients' perceptions of noncardiac chest pain.
AB  - AIMS AND OBJECTIVES: To examine patients' perceptions and experiences of
      noncardiac chest pain, within the framework of the common sense model.
      BACKGROUND: Patients with noncardiac chest pain have good physical prognosis, but
      frequently suffer prolonged pain and psychological distress. The common sense
      model may provide a good framework for examining outcomes in patients with
      noncardiac chest pain. DESIGN: Qualitative thematic analysis with semi-structured
      interviews. METHODS: In 2010, participants recruited from an emergency department
      (N = 7) with persistent noncardiac chest pain and distress were interviewed using
      a semi-structured schedule, and data were analysed using thematic analysis.
      RESULTS: Seven themes were identified; six of which mapped onto core dimensions
      of the common sense model (identity, cause, timeline, consequences, personal
      control, treatment control). Contrary to previous research on medically
      unexplained symptoms, most participants perceived psychological factors to play a
      causal role in their chest pain. Participants' perceptions largely mapped onto
      the common sense model, although there was a lack of coherence across dimensions,
      particularly with regard to cause. CONCLUSION: Patients with noncardiac chest
      pain lack understanding with regard to their condition and may be accepting of
      psychological causes of their pain. RELEVANCE TO CLINICAL PRACTICE: Brief
      psychological interventions aimed at improving understanding of the causes of
      noncardiac chest pain and providing techniques for managing pain and stress may
      be useful for patients with noncardiac chest pain.

PMID- 25988507
TI  - Combined Optical Coherence and Fluorescence Microscopy to assess dynamics and
      specificity of pancreatic beta-cell tracers.
AB  - The identification of a beta-cell tracer is a major quest in diabetes research.
      However, since MRI, PET and SPECT cannot resolve individual islets, optical
      techniques are required to assess the specificity of these tracers. We propose to
      combine Optical Coherence Microscopy (OCM) with fluorescence detection in a
      single optical platform to facilitate these initial screening steps from cell
      culture up to living rodents. OCM can image islets and vascularization without
      any labeling. Thereby, it alleviates the need of both genetically modified mice
      to detect islets and injection of external dye to reveal vascularization. We
      characterized Cy5.5-exendin-3, an agonist of glucagon-like peptide 1 receptor
      (GLP1R), for which other imaging modalities have been used and can serve as a
      reference. Cultured cells transfected with GLP1R and incubated with Cy5.5-exendin
      3 show full tracer internalization. We determined that a dose of 1 MUg of Cy5.5
      exendin-3 is sufficient to optically detect in vivo the tracer in islets with a
      high specificity. In a next step, time-lapse OCM imaging was used to monitor the
      rapid and specific tracer accumulation in murine islets and its persistence over
      hours. This optical platform represents a versatile toolbox for selecting beta
      cell specific markers for diabetes research and future clinical diagnosis. 

PMID- 25988509
TI  - Arrogance in the workplace: implications for mental health nurses.
AB  - Cultures of performativity may contribute to organizational and individual
      arrogance. Workplace organizations have individuals who at various times will
      display arrogance, which may manifest in behaviours, such as an exaggerated sense
      of self-importance, dismissiveness of others, condescending behaviors and an
      impatient manner. Arrogance is not a flattering label and irrespective of the
      reason or the position of power, in the context of organizational behaviors, may
      not be useful and may even be detrimental to the work environment. Thus, it is
      timely to reflect on the implications of arrogance in the workplace. Advocacy and
      empowerment can be undermined and relationships adversely impacted, including the
      achievement of positive consumer outcomes. This paper provides an introduction to
      arrogance, and then discusses arrogance to promote awareness of the potential
      consequences of arrogance and its constituent behaviors. 

PMID- 25988508
TI  - What can isolated skeletal muscle experiments tell us about the effects of
      caffeine on exercise performance?
AB  - Caffeine is an increasingly popular nutritional supplement due to the legal,
      significant improvements in sporting performance that it has been documented to
      elicit, with minimal side effects. Therefore, the effects of caffeine on human
      performance continue to be a popular area of research as we strive to improve our
      understanding of this drug and make more precise recommendations for its use in
      sport. Although variations in exercise intensity seems to affect its ergogenic
      benefits, it is largely thought that caffeine can induce significant improvements
      in endurance, power and strength-based activities. There are a number of
      limitations to testing caffeine-induced effects on human performance that can be
      better controlled when investigating its effects on isolated muscles under in
      vitro conditions. The hydrophobic nature of caffeine results in a post-digestion
      distribution to all tissues of the body making it difficult to accurately
      quantify its key mechanism of action. This review considers the contribution of
      evidence from isolated muscle studies to our understating of the direct effects
      of caffeine on muscle during human performance. The body of in vitro evidence
      presented suggests that caffeine can directly potentiate skeletal muscle force,
      work and power, which may be important contributors to the performance-enhancing
      effects seen in humans. 

PMID- 25988510
TI  - Hydrogen Bonding Stabilized Self-Assembly of Inorganic Nanoparticles: Mechanism
      and Collective Properties.
AB  - Developing a simple and efficient method to organize nanoscale building blocks
      into ordered superstructures, understanding the mechanism for self-assembly and
      revealing the essential collective properties are crucial steps toward the
      practical use of nanostructures in nanotechnology-based applications. In this
      study, we showed that the high-yield formation of ZnO nanoparticle chains with
      micrometer length can be readily achieved by the variation of solvents from
      methanol to water. Spectroscopic studies confirmed the solvent effect on the
      surface properties of ZnO nanoparticles, which were found to be critical for the
      formation of anisotropic assemblies. Quantum mechanical calculations and all atom
      molecular dynamic simulations indicated the contribution of hydrogen bonding for
      stabilizing the structure in water. Dissipative particle dynamics further
      revealed the importance of solvent-nanoparticle interactions for promoting one
      dimensional self-assembly. The branching of chains was found upon aging,
      resulting in the size increase of the ensembles and network formation. Steady
      state and time-resolved luminescent spectroscopes, which probed the variation of
      defect-related emission, revealed stronger Forster resonance energy transfer
      (FRET) between nanoparticles when the chain networks were formed. The high
      efficiency of FRET quenching can be ascribed to the presence of multiple energy
      transfer channels, as well as the short internanoparticle distances and the
      dipole alignment. 

PMID- 25988511
TI  - Adenocarcinoma of the appendix: a rural experience.

PMID- 25988512
TI  - Epitaxial Bi2 FeCrO6 Multiferroic Thin Film as a New Visible Light Absorbing
      Photocathode Material.
AB  - Ferroelectric materials have been studied increasingly for solar energy
      conversion technologies due to the efficient charge separation driven by the
      polarization induced internal electric field. However, their insufficient
      conversion efficiency is still a major challenge. Here, a photocathode material
      of epitaxial double perovskite Bi(2) FeCrO(6) multiferroic thin film is reported
      with a suitable conduction band position and small bandgap (1.9-2.1 eV), for
      visible-light-driven reduction of water to hydrogen. Photoelectrochemical
      measurements show that the highest photocurrent density up to -1.02 mA cm(-2) at
      a potential of -0.97 V versus reversible hydrogen electrode is obtained in p-type
      Bi(2) FeCrO(6) thin film photocathode grown on SrTiO(3) substrate under AM 1.5G
      simulated sunlight. In addition, a twofold enhancement of photocurrent density is
      obtained after negatively poling the Bi(2) FeCrO(6) thin film, as a result of
      modulation of the band structure by suitable control of the internal electric
      field gradient originating from the ferroelectric polarization in the Bi(2)
      FeCrO(6) films. The findings validate the use of multiferroic Bi(2) FeCrO(6) thin
      films as photocathode materials, and also prove that the manipulation of internal
      fields through polarization in ferroelectric materials is a promising strategy
      for the design of improved photoelectrodes and smart devices for solar energy
      conversion.

PMID- 25988513
TI  - The new LNG-releasing IUS: a new opportunity to reduce the burden of unintended
      pregnancy.
AB  - Unintended pregnancies still remain a worldwide public health problem. They have
      received much attention in adolescents given the strong impact they have on their
      present and future lives. Young women wishing to delay maternity are also
      especially vulnerable to unintended pregnancies. Studies have revealed a pattern
      of use of contraceptive methods that is likely to increase this risk. Methods of
      long-acting reversible contraception (LARC), among which copper and
      levonorgestrel-releasing intrauterine devices (IUD and IUS) are the most common,
      have been widely recommended to avoid unintended pregnancy at any age. Despite
      this, the use of these devices is very limited. Several barriers to their wide
      spread use have been identified, which specially affect a higher use by
      nulliparous women. A new levonorgestrel-releasing IUS containing only 13.5mg of
      levonorgestrel (IUS12) recently marketed as Jaydess(r) in Europe, has a smaller
      size, provides a shorter duration of action, and a lower hormonal content
      compared to Mirena(r), along with a similar efficacy and safety profile, may
      offer a long-term option that better addresses the needs of nulliparous women.
      Evidence on the risk of unintended pregnancies in young women--with a special
      emphasis in Europe, barriers associated with a lower-than-desirable use of LARC
      methods--especially intrauterine devices (IUD and IUS), and the potential
      benefits of the new IUS12 including changes in bleeding pattern, safety and user
      satisfaction--especially with respect to nulliparous and adolescents--are
      reviewed here. Evidence supports that IUS12 may offer a LARC option that better
      addresses the needs of these women.

PMID- 25988514
TI  - Menopausal stages and non-alcoholic fatty liver disease in middle-aged women.
AB  - OBJECTIVES: There is no established evidence regarding the influence of the
      menopausal transition period on non-alcoholic fatty liver disease (NAFLD). The
      goal of this study was to examine the association between menopausal stages and
      the prevalence of NAFLD in middle-aged Korean women. METHODS: This study was a
      cross-sectional analysis of 1559 women aged 44-56 years, who underwent a
      comprehensive health screening examination in the Kangbuk Samsung Hospital Total
      Healthcare Centers during 2012 and 2013. Information regarding menopause status
      was collected using a standardized, self-administered questionnaire. The presence
      of fatty liver was determined using ultrasonography. Menopausal stages were
      defined according to the criteria of the Stages of Reproductive Aging Workshop
      (STRAW+10) as follows: early menopausal transition was defined as a persistent
      difference in consecutive menstrual cycle length of seven or more days; late
      menopausal transition was defined as having an interval of amenorrhea of 60 days
      or more; post-menopause was defined as the absence of menstrual periods for 12 or
      more months since the last period; pre-menopause was defined as having a regular
      menstrual cycle and not meeting the above criteria. Odds ratios and 95%
      confidence intervals for NAFLD were estimated by menopausal stages. RESULTS: Of
      the 1559 women, 334 had NAFLD. A higher prevalence of NAFLD was observed across
      menopausal stages (p for trend <0.05). After adjusting for age, center, BMI,
      smoking status, alcohol intake, physical activity, educational level, parity and
      age at menarche, the odds ratios (95% CIs) for NAFLD comparing early transition,
      late transition, and post-menopause to pre-menopause were 1.07 (0.68-1.67), 1.87
      (1.23-2.85), and 1.67 (1.01-2.78), respectively. CONCLUSIONS: This study
      performed in middle-aged Korean women suggests that there is an increased
      prevalence of NAFLD in the late menopausal transition as well as post-menopausal
      stages, independent of a variety of potential confounders. The findings of this
      study suggest that early intervention strategies implemented before women begin
      to experience the menopausal transition are needed to reduce the risk of NAFLD.

PMID- 25988515
TI  - Impact of iron-reducing bacteria on the corrosion rate of carbon steel under
      simulated geological disposal conditions.
AB  - The current projects for the disposal of high-level radioactive waste rely on
      underground burial and confinement by metallic envelopes that are susceptible to
      corrosion processes. The impact of microbial activity must be fully clarified in
      order to provide biological parameters for predictive reactive transport models.
      This study investigates the impact of hydrogenotrophic iron-reducing bacteria
      (Shewanella oneidensis strain MR-1) on the corrosion rate of carbon steel under
      simulated geological disposal conditions by using a geochemical approach. It was
      found that corrosion damage changes mostly according to the experimental solution
      (i.e., chemical composition). Magnetite and vivianite were identified as the main
      corrosion products. In the presence of bacteria, the corrosion rate increased by
      a factor of 1.3 (according to weight loss analysis) to 1.8 (according to H2
      measurements), and the detected amount of magnetite diminished. The mechanism
      likely to enhance corrosion is the destabilization and dissolution of the
      passivating magnetite layer by reduction of structural Fe(III) coupled to H2
      oxidation.

PMID- 25988516
TI  - Nephrocalcinosis in Calcium Stone Formers Who Do Not have Systemic Disease.
AB  - PURPOSE: Nephrocalcinosis is commonly present in primary hyperparathyroidism,
      distal renal tubular acidosis and medullary sponge kidney disease. To our
      knowledge it has not been studied in patients with calcium phosphate stones who
      do not have systemic disease. MATERIALS AND METHODS: We studied patients
      undergoing percutaneous nephrolithotomy who had calcium phosphate or calcium
      oxalate stones and did not have hyperparathyroidism, distal renal tubular
      acidosis or medullary sponge kidney disease. On postoperative day 1 all patients
      underwent noncontrast computerized tomography. If there were no residual
      calcifications, the patient was categorized as not having nephrocalcinosis. If
      there were residual calcifications, the patient underwent secondary percutaneous
      nephrolithotomy. If the calcifications were found to be stones, the patient was
      categorized as not having nephrocalcinosis. If the calcifications were not
      stones, the patient was categorized as having nephrocalcinosis. Patients were
      grouped based on the type of stones that formed, including hydroxyapatite,
      brushite and idiopathic calcium oxalate. The extent of nephrocalcinosis was
      quantified as 0--absent nephrocalcinosis to 3--extensive nephrocalcinosis.
      Patients with residual calcifications on postoperative day 1 noncontrast
      computerized tomography who did not undergo secondary percutaneous
      nephrolithotomy were excluded from analysis. The presence or absence of
      nephrocalcinosis was correlated with metabolic studies. RESULTS: A total of 67
      patients were studied, including 14 with hydroxyapatite, 19 with brushite and 34
      with idiopathic calcium oxalate calculi. Nephrocalcinosis was present in 10 of 14
      (71.4%), 11 of 19 (57.9%) and 6 of 34 patients (17.6%) in the hydroxyapatite,
      brushite and idiopathic calcium oxalate groups, respectively (chi-square p =
      0.01). The mean extent of nephrocalcinosis per group was 1.98, 1.32 and 0.18 for
      hydroxyapatite, brushite and idiopathic calcium oxalate, respectively (p
      <=0.001). The presence of nephrocalcinosis positively correlated with urine
      calcium excretion (mean +/- SD 287.39 +/- 112.49 vs 223.68 +/- 100.67 mg per day,
      p = 0.03). CONCLUSIONS: Patients without systemic disease who form hydroxyapatite
      and brushite stones commonly have coexistent nephrocalcinosis. Nephrocalcinosis
      can occur in calcium oxalate stone formers but the quantity and frequency of
      nephrocalcinosis in this group are dramatically less.

PMID- 25988517
TI  - The Ohmmeter Identifies the Site of Fluid Leakage during Artificial Urinary
      Sphincter Revision Surgery.
AB  - PURPOSE: While the AMS 800 artificial urinary sphincter improves continence in up
      to 90% of patients, revision surgery may be needed in up to 50%. We determined
      whether an ohmmeter could accurately assess the site of fluid leak from
      individual components of the artificial urinary sphincter at the time of revision
      surgery. MATERIALS AND METHODS: We retrospectively reviewed the records of
      patients who underwent artificial urinary sphincter revision surgery between 1996
      and 2013. Patients in whom fluid loss was identified preoperatively by plain film
      radiography and who subsequently underwent revision surgery using the ohmmeter
      were assessed for outcomes. RESULTS: The ohmmeter was used intraoperatively in a
      total of 20 surgeries in 19 patients and it correctly identified the location of
      fluid loss in 18 of 20 (90%). Fluid leakage was found from the pressure
      regulating balloon in 13 cases, from the cuff in 4 and from the tubing to the
      pressure regulating balloon in 1. None had fluid loss from the pump. In the 17
      cases in which only the malfunctioning component was replaced a satisfactory
      postoperative outcome with a fully functional device was documented in all.
      Repeat surgery was performed in 5 of 17 cases (29.4%) at a median of 17 months
      (range 2 to 39). No patient underwent repeat surgery due to failure to accurately
      diagnose a component leak. CONCLUSIONS: In cases of suspected fluid loss as a
      cause of artificial urinary sphincter malfunction an ohmmeter can identify the
      site of fluid loss during component revision surgery.

PMID- 25988518
TI  - Baseline Perineural Invasion is Associated with Shorter Time to Progression in
      Men with Prostate Cancer Undergoing Active Surveillance: Results from the REDEEM
      Study.
AB  - PURPOSE: We evaluated the association of perineural invasion with disease
      progression in men with prostate cancer on active surveillance. MATERIALS AND
      METHODS: We retrospectively analyzed the records of 302 men on active
      surveillance for low risk prostate cancer (T1c-T2a), Gleason 6 or less, 3 or
      fewer positive cores, 50% or less of any core involved and prostate specific
      antigen 11 ng/ml or less in the REduction by Dutasteride of clinical progression
      Events in Expectant Management (REDEEM) study. Patients underwent study mandated
      biopsies 18 and 36 months after enrollment. Disease progression was divided into
      pathological (4 or greater positive cores, 50% or greater core involvement, or
      Gleason greater than 6 on followup biopsy), therapeutic (any therapeutic prostate
      cancer intervention) or clinical (pathological or therapeutic progression). Time
      to disease progression was analyzed with Cox models adjusting for patient age,
      race, baseline prostate specific antigen, number of sampled and involved cores,
      tumor length and treatment. RESULTS: A total of 11 patients (4%) had perineural
      invasion on baseline biopsy. Perineural invasion was not associated with any
      baseline features (each p >0.05). During the study clinical progression developed
      in 125 patients (41%), including pathological progression in 95. One, 2 and 3
      year clinical progression-free survival for men with vs without perineural
      invasion was 82%, 27% and 27% vs 93%, 67% and 58%, respectively (p <0.05). On
      multivariable analyses perineural invasion was associated with clinical (HR 2.39,
      95% CI 1.16-4.94, p = 0.019) and pathological progression (HR 2.21, 95% CI 0.92
      5.33, p = 0.076). CONCLUSIONS: Among patients with prostate cancer on active
      surveillance perineural invasion was associated with an increased risk of
      clinical progression. The 2-year risk of clinical progression with perineural
      invasion was 73%. If these results are confirmed, patients with perineural
      invasion may not be good active surveillance candidates.

PMID- 25988520
TI  - Antitumor and antimicrobial activity of some cyclic tetrapeptides and tripeptides
      derived from marine bacteria.
AB  - Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu) was selected as a lead to evaluate
      antitumor-antibiotic activity. Histidine was chosen to replace the serine residue
      to form cyclo(Gly-l-His-l-Pro-l-Glu). Cyclic tetrapeptides (CtetPs) were then
      synthesized using a solution phase method, and subjected to antitumor and
      antibiotic assays. The benzyl group protected CtetPs derivatives, showed better
      activity against antibiotic-resistant Staphylococcus aureus in the range of 60
      120 MUM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity
      against several cell lines at a concentration of 80-108 MUM. However, shortening
      the size of the ring to the cyclic tripeptide (CtriP) scaffold, cyclo(Gly-l-Ser-l
      Pro), cyclo(Ser-l-Pro-l-Glu) and their analogues showed no antibiotic or
      antitumor activity. This phenomenon can be explained from their backbone
      structures. 

PMID- 25988521
TI  - Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF
      BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells.
AB  - Dihydroaustrasulfone alcohol (DA), an active compound firstly isolated from
      marine corals, has been reported to reveal anti-cancer and anti-inflammation
      activities. These reported activities of DA raised a possible application in anti
      restenosis. Abnormal proliferation and migration of vascular smooth muscle cells
      (VSMCs) and the stimulation of platelet-derived growth factor (PDGF)-BB play
      major pathological processes involved in the development of restenosis.
      Experimental results showed that DA markedly reduced balloon injury-induced
      neointima formation in the rat carotid artery model and significantly inhibited
      PDGF-BB-stimulated proliferation and migration of VSMCs. Our data further
      demonstrated that translational and active levels of several critical signaling
      cascades involved in VSMC proliferation, such as extracellular signal-regulated
      kinase/ mitogen-activated protein kinases (ERK/MAPK), phosphatidylinositol 3
      kinase (PI3K)/AKT, and signal transducer and activator of transcription (STAT),
      were obviously inhibited. In addition, DA also decreased the activation and
      expression levels of gelatinases (matrix metalloproteinase (MMP)-2 and MMP-9)
      involved in cell migration. In conclusion, our findings indicate that DA can
      reduce balloon injury-neointimal hyperplasia, the effect of which may be
      modulated through suppression of VSMC proliferation and migration. These results
      suggest that DA has potential application as an anti-restenotic agent for the
      prevention of restenosis. 

PMID- 25988522
TI  - SAR of Sponge-Inspired Hemibastadin Congeners Inhibiting Blue Mussel
      PhenolOxidase.
AB  - Hemibastadin derivatives, including the synthetically-derived 5,5'
      dibromohemibastadin-1 (DBHB), are potent inhibitors of blue mussel phenoloxidase
      (PO), which is a key enzyme involved in the firm attachment of this invertebrate
      to substrates and, thus, a promising molecular target for anti-fouling research.
      For a systematic investigation of the enzyme inhibitory activity of hemibastadin
      derivatives, we have synthesized nine new congeners, which feature structural
      variations of the DBHB core structure. These structural modifications include,
      e.g., different halogen substituents present at the aromatic rings, different
      amine moieties linked to the (E)-2-(hydroxyimino)-3-(4-hydroxyphenyl)propionic
      acid, the presence of free vs. substituted aromatic hydroxyl groups and a free
      vs. methylated oxime group. All compounds were tested for their inhibitory
      activity towards the target enzyme in vitro, and IC50 values were calculated.
      Derivatives, which structurally closely resemble sponge-derived hemibastadins,
      revealed superior enzyme inhibitory properties vs. congeners featuring structural
      moieties that are absent in the respective natural products. This study suggests
      that natural selection has yielded structurally-optimized antifouling compounds. 

PMID- 25988523
TI  - Antidiabetic activity of differently regioselective chitosan sulfates in alloxan
      induced diabetic rats.
AB  - The present study investigated and compared the hypoglycemic activity of
      differently regioselective chitosan sulfates in alloxan-induced diabetic rats.
      Compared with the normal control rats, significantly higher blood glucose levels
      were observed in the alloxan-induced diabetic rats. The differently
      regioselective chitosan sulfates exhibited hypoglycemic activities at different
      doses and intervals, especially 3-O-sulfochitosan (3-S). The major results are as
      follows. First, 3,6-di-O-sulfochitosan and 3-O-sulfochitosan exhibited more
      significant hypoglycemic activities than 2-N-3, 6-di-O-sulfochitosan and 6-O
      sulfochitosan. Moreover, 3-S-treated rats showed a more significant reduction of
      blood glucose levels than those treated by 3,6-di-O-sulfochitosan. These results
      indicated that -OSO3- at the C3-position of chitosan is a key active site.
      Second, 3-S significantly reduced the blood glucose levels and regulated the
      glucose tolerance effect in the experimental rats. Third, treatment with 3-S
      significantly increased the plasma insulin levels in the experimental diabetic
      rats. A noticeable hypoglycemic activity of 3-S in the alloxan-induced diabetic
      rats was shown. Clinical trials are required in the future to confirm the utility
      of 3-S. 

PMID- 25988519
TI  - Marine polysaccharides from algae with potential biomedical applications.
AB  - There is a current tendency towards bioactive natural products with applications
      in various industries, such as pharmaceutical, biomedical, cosmetics and food.
      This has put some emphasis in research on marine organisms, including macroalgae
      and microalgae, among others. Polysaccharides with marine origin constitute one
      type of these biochemical compounds that have already proved to have several
      important properties, such as anticoagulant and/or antithrombotic,
      immunomodulatory ability, antitumor and cancer preventive, antilipidaemic and
      hypoglycaemic, antibiotics and anti-inflammatory and antioxidant, making them
      promising bioactive products and biomaterials with a wide range of applications.
      Their properties are mainly due to their structure and physicochemical
      characteristics, which depend on the organism they are produced by. In the
      biomedical field, the polysaccharides from algae can be used in controlled drug
      delivery, wound management, and regenerative medicine. This review will focus on
      the biomedical applications of marine polysaccharides from algae. 

PMID- 25988525
TI  - A transportable, inexpensive electroporator for in utero electroporation.
AB  - Electroporation is a useful technique to study gene function during development
      but its broad application is hampered due to the expensive equipment needed. We
      describe the construction of a transportable, simple and inexpensive
      electroporator delivering square pulses with varying length and amplitude. The
      device was successfully used for in utero electroporation in mouse with a
      performance comparable to that of commercial products.

PMID- 25988526
TI  - Hyperbaric Oxygen Therapy: A New Treatment for Chronic Pain?
AB  - BACKGROUND AND OBJECTIVE: Hyperbaric oxygen therapy (HBOT) is a treatment
      providing 100% oxygen at a pressure greater than that at sea level. HBOT is
      becoming increasingly recognized as a potential treatment modality for a broad
      range of ailments, including chronic pain. In this narrative review, we discuss
      the current understanding of pathophysiology of nociceptive, inflammatory and
      neuropathic pain, and the body of animal studies addressing mechanisms by which
      HBOT may ameliorate these different types of pain. Finally, we review clinical
      studies suggesting that HBOT may be useful in treating chronic pain syndromes,
      including chronic headache, fibromyalgia, complex regional pain syndrome, and
      trigeminal neuralgia. DATABASE AND DATA TREATMENT: A comprehensive search through
      MEDLINE, EMBASE, Scopus, and Web of Science for studies relating to HBOT and pain
      was performed using the following keywords: hyperbaric oxygen therapy or
      hyperbaric oxygen treatment (HBOT), nociceptive pain, inflammatory pain,
      neuropathic pain, HBOT AND pain, HBOT AND headache, HBOT AND fibromyalgia, HBOT
      AND complex regional pain syndrome, and HBOT AND trigeminal neuralgia. RESULTS:
      Twenty-five studies examining the role of HBOT in animal models of pain and human
      clinical trials were found and reviewed for this narrative review. CONCLUSIONS:
      HBOT has been shown to reduce pain using animal models. Early clinical research
      indicates HBOT may also be useful in modulating human pain; however, further
      studies are required to determine whether HBOT is a safe and efficacious
      treatment modality for chronic pain conditions.

PMID- 25988524
TI  - RSK3: A regulator of pathological cardiac remodeling.
AB  - The family of p90 ribosomal S6 kinases (RSKs) are pleiotropic effectors for
      extracellular signal-regulated kinase signaling pathways. Recently, RSK3 was
      shown to be important for pathological remodeling of the heart. Although cardiac
      myocyte hypertrophy can be compensatory for increased wall stress, in chronic
      heart diseases, this nonmitotic cell growth is usually associated with
      interstitial fibrosis, increased cell death, and decreased cardiac function.
      Although RSK3 is less abundant in the cardiac myocyte than other RSK family
      members, RSK3 appears to serve a unique role in cardiac myocyte stress responses.
      A potential mechanism conferring the unique function of RSK3 in the heart is
      anchoring by the scaffold protein muscle A-kinase anchoring protein beta
      (mAKAPbeta). Recent findings suggest that RSK3 should be considered as a
      therapeutic target for the prevention of heart failure, a clinical syndrome of
      major public health significance.

PMID- 25988528
TI  - Conjunctival extranodal marginal zone B-cell lymphoma with crystal-storing
      histiocytosis.

PMID- 25988530
TI  - PMMA functionalized boron nitride sheets as nanofillers.
AB  - We report the functionalization of hexagonal boron nitride (hBN) with polymer
      chains. These chains are grown by atom transfer radical polymerization (ATRP)
      from hBN following thermal treatment. When used as a nanofiller, the material
      shows improved dispersion resulting in significantly improved toughness as
      compared to pristine hBN without polymer functionalization. The polymer
      functionalized BN is also characterized by TGA, FTIR and FESEM. 

PMID- 25988527
TI  - Shaping mitotic chromosomes: From classical concepts to molecular mechanisms.
AB  - How eukaryotic genomes are packaged into compact cylindrical chromosomes in
      preparation for cell divisions has remained one of the major unsolved questions
      of cell biology. Novel approaches to study the topology of DNA helices inside the
      nuclei of intact cells, paired with computational modeling and precise
      biomechanical measurements of isolated chromosomes, have advanced our
      understanding of mitotic chromosome architecture. In this Review Essay, we
      discuss - in light of these recent insights - the role of chromatin architecture
      and the functions and possible mechanisms of SMC protein complexes and other
      molecular machines in the formation of mitotic chromosomes. Based on the
      information available, we propose a stepwise model of mitotic chromosome
      condensation that envisions the sequential generation of intra-chromosomal
      linkages by condensin complexes in the context of cohesin-mediated inter
      chromosomal linkages, assisted by topoisomerase II. The described scenario
      results in rod-shaped metaphase chromosomes ready for their segregation to the
      cell poles. 

PMID- 25988529
TI  - Repeated forced swim stress differentially affects formalin-evoked nociceptive
      behaviour and the endocannabinoid system in stress normo-responsive and stress
      hyper-responsive rat strains.
AB  - Repeated exposure to a homotypic stressor such as forced swimming enhances
      nociceptive responding in rats. However, the influence of genetic background on
      this stress-induced hyperalgesia is poorly understood. The aim of the present
      study was to compare the effects of repeated forced swim stress on nociceptive
      responding in Sprague-Dawley (SD) rats versus the Wistar Kyoto (WKY) rat strain,
      a genetic background that is susceptible to stress, negative affect and
      hyperalgesia. Given the well-documented role of the endocannabinoid system in
      stress and pain, we investigated associated alterations in endocannabinoid
      signalling in the dorsal horn of the spinal cord and amygdala. In SD rats,
      repeated forced swim stress for 10 days was associated with enhanced late phase
      formalin-evoked nociceptive behaviour, compared with naive, non-stressed SD
      controls. In contrast, WKY rats exposed to 10 days of swim stress displayed
      reduced late phase formalin-evoked nociceptive behaviour. Swim stress increased
      levels of monoacylglycerol lipase (MAGL) mRNA in the ipsilateral side of the
      dorsal spinal cord of SD rats, an effect not observed in WKY rats. In the
      amygdala, swim stress reduced anandamide (AEA) levels in the contralateral
      amygdala of SD rats, but not WKY rats. Additional within-strain differences in
      levels of CB1 receptor and fatty acid amide hydrolase (FAAH) mRNA and levels of 2
      arachidonylglycerol (2-AG) were observed between the ipsilateral and
      contralateral sides of the dorsal horn and/or amygdala. These data indicate that
      the effects of repeated stress on inflammatory pain-related behaviour are
      different in two rat strains that differ with respect to stress responsivity and
      affective state and implicate the endocannabinoid system in the spinal cord and
      amygdala in these differences.

PMID- 25988533
TI  - A National Survey Assessing the Current Workforce of Transplant Pharmacists
      Across Accredited U.S. Solid Organ Transplant Programs.
AB  - Integration of pharmacists into multidisciplinary transplant patient care has
      advanced in recent years, with limited data available to evaluate the current
      status of the profession. This was a national survey developed as an AST Pharmacy
      COP initiative. Responses were solicited from pharmacists practicing at U.S.
      transplant programs based on UNOS listing; 176 participants from 113 centers
      (41%) responded, with 79% practicing <=10 years. There is a median of 1.4
      pharmacist full-time equivalents (FTEs) (range 0.1-7.1) for every 100
      transplants. The predominant activities performed by pharmacists during the
      transplant phase include medication review (95%), lab review (92%), allergy
      review (88%), medication therapy management (92%), bedside rounds (87%),
      medication education (79%), documentation (71%), and coordinating discharge
      medications (58%). Similar activities were reported during the other phases, but
      participation was less common. The involvement of dedicated transplant
      pharmacists within multidisciplinary care has become standard at a large number
      of centers, although expansion is still needed to ensure core pharmaceutical care
      components are provided to all transplant recipients across all centers. These
      results inform on the typical responsibilities of pharmacists practicing within
      the field of transplantation and illustrate that the level of pharmacist
      involvement significantly varies across transplant centers and the phases of
      transplantation. 

PMID- 25988532
TI  - Expression and purification of a single-chain Type IV restriction enzyme
      Eco94GmrSD and determination of its substrate preference.
AB  - The first reported Type IV restriction endonuclease (REase) GmrSD consists of
      GmrS and GmrD subunits. In most bacteria, however, the gmrS and gmrD genes are
      fused together to encode a single-chain protein. The fused coding sequence for
      ECSTEC94C_1402 from E. coli strain STEC_94C was expressed in T7 Express. The
      protein designated as Eco94GmrSD displays modification-dependent ATP-stimulated
      REase activity on T4 DNA with glucosyl-5-hydroxymethyl-cytosines (glc-5hmC) and
      T4gt DNA with 5-hydroxymethyl-cytosines (5hmC). A C-terminal 6xHis-tagged protein
      was purified by two-column chromatography. The enzyme is active in Mg(2+) and
      Mn(2+) buffer. It prefers to cleave large glc-5hmC- or 5hmC-modified DNA. In
      phage restriction assays, Eco94GmrSD weakly restricted T4 and T4gt, whereas T4
      IPI*-deficient phage (Deltaip1) were restricted more than 10(6)-fold, consistent
      with IPI* protection of E. coli DH10B from lethal expression of the closely
      homologous E. coli CT596 GmrSD. Eco94GmrSD is proposed to belong to the His-Asn
      His (HNH)-nuclease family by the identification of a putative C-terminal REase
      catalytic site D507-H508-N522. Supporting this, GmrSD variants D507A, H508A, and
      N522A displayed no endonuclease activity. The presence of a large number of fused
      GmrSD homologs suggests that GmrSD is an effective phage exclusion protein that
      provides a mechanism to thwart T-even phage infection. 

PMID- 25988531
TI  - Differential dependence on nuclear factor-kappaB-inducing kinase among natural
      killer T-cell subsets in their development.
AB  - Natural killer T cells (NKT cells) are comprised of several subsets. However, the
      possible differences in their developmental mechanisms have not been fully
      investigated. To evaluate the dependence of some NKT subpopulations on nuclear
      factor-kappaB-inducing kinase (NIK) for their generation, we analysed the
      differentiation of NKT cells, dividing them into subsets in various tissues of
      alymphoplasia (aly/aly), a mutant mouse strain that lacks functional NIK. The
      results indicated that the efficient differentiation of both invariant NKT (iNKT)
      and non-iNKT cells relied on NIK expression in non-haematopoietic cells; however,
      the dependence of non-iNKT cells was lower than that of iNKT cells. Especially,
      the differentiation of CD8(+) non-iNKT cells was markedly resistant to the aly
      mutation. The proportion of two other NKT cell subsets, NK1.1(+) gammadelta T
      cells and NK1.1(-) iNKT cells, was also significantly reduced in aly/aly mice,
      and this defect in their development was reversed in wild-type host mice given
      aly/aly bone marrow cells. In exerting effector functions, NIK in NKT-alphabeta
      cells appeared dispensable, as NIK-deficient NKT-alphabeta cells could secrete
      interleukin-4 or interferon-gamma and exhibit cytolytic activity at a level
      comparable to that of aly/+ NKT-alphabeta cells. Collectively, these results
      imply that the NIK in thymic stroma may be critically involved in the
      differentiation of most NKT cell subsets (although the level of NIK dependence
      may vary among the subsets), and also that NIK in NKT-alphabeta cells may be
      dispensable for their effector function.

PMID- 25988534
TI  - Edible films and coatings based on biodegradable residues applied to acerolas
      (Malpighia punicifolia L.).
AB  - BACKGROUND: This study aimed to produce and characterize edible films and
      coatings from fruit and vegetable residue (FVR) flour and potato peel (P) flour.
      Two coating approaches (immersion and film) were studied on the quality of
      acerolas. RESULTS: Film-forming solutions (FFS) presented a viscoelastic behavior
      and a gelation process occurring at 70  degrees C. Maximum density (1.018 g cm(
      3) ), viscosity (44.404 cP) and starch content were obtained for FFS based on 8%
      FVR flour with 4% P flour. This same film presented enhanced mechanical
      properties such as tensile strength and elongation at break (0.092 MPa and 36%
      respectively). Solubility of the films averaged 87%, demonstrating high
      hydrophilicity. Improved performance was obtained for film-packaged acerolas,
      which exhibited an increase in shelf life of 50% compared with control fruits. A
      lower loss of weight was observed for these samples by about 30-57% compared with
      control fruits, but minor modifications of pH, titratable acidity and soluble
      solid content occurred during storage. CONCLUSION: This study demonstrated the
      potential of FVR flour for edible coating and film formulation. Practical
      application on acerolas constituted a motivating route to evaluate and optimize
      this process; however, microbiological and sensory analyses are necessary to
      assess the material acceptability and safety.

PMID- 25988535
TI  - Water-Soluble Ruthenium(II) Complexes with Chiral 4-(2,3-Dihydroxypropyl)
      formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by
      Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and
      Induction of Tumor Cell Apoptosis.
AB  - Three water-soluble ruthenium(II) complexes with chiral 4-(2,3-dihydroxypropyl)
      formamide oxoaporphine (FOA) were synthesized and characterized. It was found
      that these ruthenium(II) complexes exhibited considerable in vitro anticancer
      activities and that they were the effective stabilizers of telomeric and G
      quadruplex-DNA (G4-DNA) in promoter of c-myc, which acted as a telomerase
      inhibitor targeting G4-DNA and induced cell senescence and apoptosis.
      Interestingly, the in vitro anticancer activity of 6 (LC-003) was higher than
      those of 4 (LC-001) and 5 (LC-002), more selective for BEL-7404 cells than for
      normal HL-7702 cells, and preferred to activate caspases-3/9. The different
      biological behaviors of the ruthenium complexes could be correlated with the
      chiral nature of 4-(2,3-dihydroxypropyl)-formamide oxoaporphine. More
      significantly, 6 exhibited effective inhibitory on tumor growth in BEL-7402
      xenograft mouse model and higher in vivo safety than cisplatin. These mechanistic
      insights indicate that 6 displays low toxicity and can be a novel anticancer drug
      candidate. 

PMID- 25988536
TI  - Interoceptive exposure exercises for social anxiety.
AB  - Individuals with social anxiety disorder (SAD) commonly experience panic attacks
      and evidence increased anxiety sensitivity (AS) specific to noticeable anxiety
      sensations. Interoceptive exposure (IE) is an effective treatment for reducing
      AS, but few IE tasks target fears of blushing, sweating, or trembling, which are
      incorporated within AS social concerns and especially feared by individuals with
      SAD. The primary study aims were trifold: (1) identify novel IE tasks that
      produce blushing, sweating, and/or trembling; (2) assess the intensity of
      sensations and anxiety produced by a series of novel and validated IE tasks; and
      (3) evaluate the incremental validity of combining an IE task and a speech task.
      Individuals (N = 55) with heightened fear of noticeably blushing, sweating,
      and/or trembling completed a control task and 8 IE tasks (e.g., hot sauce,
      hyperventilation). All tasks produced greater intensity of anxiety and sensations
      compared to the control task (ps < .001; range of eta(p)(2) = .20-.50). Responses
      to the combination of an IE task and social task compared to a social task alone
      did not differ significantly. Future directions for research and clinical
      implications of the findings are discussed.

PMID- 25988537
TI  - Eating disorders in individuals with type 1 diabetes: case series and day
      hospital treatment outcome.
AB  - Women with type 1 diabetes are at high risk for eating disorders (ED), a
      combination that can increase medical complications and mortality. As little is
      known about treatment response in this population, clinical presentation and
      treatment outcome in an extended case series were assessed. A chart review at the
      Eating Disorders Day Hospital Program at Toronto General Hospital identified a
      total of 100 individuals with type 1 diabetes assessed 1990-2012. Of 37 who
      attended day hospital, most experienced improvement in ED symptoms, but only
      18.8% had a good immediate treatment outcome, while 43.8% had an intermediate
      outcome and 37.5% had a poor outcome (meeting diagnostic criteria at discharge).
      This is poorer than program outcomes in individuals without diabetes (chi(2)  =
      12.2, df = 2; p = 0.002). Factors influencing treatment engagement and outcome
      must be further studied and used to improve treatment results in this high-risk
      group.

PMID- 25988538
TI  - An Intracranial Petri Dish? Formation of Abscess in Prior Large Stroke After
      Decompressive Hemicraniectomy.
AB  - OBJECTIVE: Development of brain abscess after an infarction is a rare clinical
      condition. There have been 11 cases in the literature. Many patients were treated
      with potent antibiotics only and did not survive. We present 2 cases in which
      patients received aggressive surgical resection of brain abscess and survived.
      The analysis of the literature confirmed our finding that surgical intervention
      of brain abscess in patients after stroke is advisable. METHODS: A 58-year-old
      man was transferred to our institution with left hemiparesis, hemisensory loss,
      neglect, and hemianopsia. The computed tomography angiography demonstrated large
      volume right hemispheric infarct. He underwent decompressive hemicraniectomy but
      developed fevers and swollen fontanelle 6 weeks later, which did not improve with
      antibiotics. The magnetic resonance imaging demonstrated progression of ring
      enhancement of the old infarct and abscess formation was suspected. In another
      case, a 42-year-old woman was admitted to our institution with aphasia and
      weakness on the right side. The computed tomography angiography showed left
      middle cerebral artery territory infarction and decompressive hemicraniectomy was
      performed. Patient recovered well but a brain abscess was suspected during a
      routine preoperative computed tomography before cranioplasty. RESULTS: In the
      first case, patient was then taken to the operating room for resection of the
      infarcted brain tissue involved. The patient's consciousness improved, and he was
      discharged with antibiotic treatment. The patient subsequently underwent
      cranioplasty with synthetic graft with no complications. In the second case, the
      suspected abscess was resected surgically and culture of abscess grew Pantoea
      agglomerans and Bacillus macerans. The patient underwent synthetic cranioplasty 1
      month later and remained in good condition. CONCLUSIONS: Secondary abscess
      formation after significant ischemic stroke is a rare condition that carries
      potential for high morbidity/mortality. The limited body of literature with the
      addition of our 2 cases supports aggressive management with surgical evacuation
      of brain abscess to increase survival.

PMID- 25988539
TI  - Radiosurgery and Seizures in Cerebral Arteriovenous Malformation.

PMID- 25988540
TI  - Vascular endothelial function is improved by oral glycine treatment in aged rats.
AB  - Glycine has been used to reduce oxidative stress and proinflammatory mediators in
      some metabolic disorders; however, its effect on the vasculature has been poorly
      studied. The aim of this work was to explore the effect of glycine on endothelial
      dysfunction in aged rats. Aortic rings with intact or denuded endothelium were
      obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15
      months of age. Concentration-response curves to phenylephrine (PHE) were obtained
      from aortic rings incubated with N(G)-nitro-l-arginine methyl ester (l-NAME),
      superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA
      expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4),
      cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)
      alpha, and interleukin-1 beta was measured by real time RT-PCR. The endothelial
      modulation of the contraction by PHE was decreased in aortic rings from aged
      rats. Glycine treatment improved this modulator effect and increased relaxation
      to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l
      NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC
      560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the
      expression of COX-2 and TNF-alpha. Glycine improved the endothelium function in
      aged rats possibly by enhancing eNOS expression and reducing the role of
      superoxide anion and contractile prostanoids that increase the nitric oxide
      bioavailability. 

PMID- 25988541
TI  - Ischemic heart disease, prescription of optimal medical therapy and geriatric
      syndromes in community-dwelling older men: A population-based study.
AB  - BACKGROUND: Guideline recommended management of ischemic heart disease (IHD)
      suggests the concomitant use of antiplatelet, beta-blocker, renin angiotensin
      system blocker and statin therapy. In older people exposure to multiple
      medications has been associated with adverse events and geriatric syndromes. The
      study aimed to investigate the use of medications for IHD in older men with and
      without geriatric syndromes, and whether adherence to medication guidelines
      impacts on adverse outcomes. METHODS: Community-dwelling men, aged >= 70 years
      and enrolled in the Concord Health and Ageing in Men Project were studied. Data
      on self-reported IHD, number of guideline recommended medications (use of four
      guideline medications considered optimal medical therapy) and geriatric syndromes
      (frailty, falls, cognitive impairment and urinary incontinence) were obtained.
      Cox regression was used to assess the relationship between optimal medical
      therapy and adverse outcomes (mortality and institutionalization), stratifying by
      geriatric syndromes. RESULTS: At baseline, 462 (27%) men self-reported a history
      of IHD and of these, 226 (49%) had at least one geriatric syndrome. Among men
      with IHD, no significant difference was observed in patterns of prescribing
      between those with and without geriatric syndromes. Compared to zero medications,
      optimal medical therapy among men with IHD was associated with lower mortality
      [hazard ratio, HR = 0.40 (95% CI: 0.21-0.95)] and institutionalization risk
      (HR=0.31; 95% CI: 0.09-0.81). The presence of geriatric syndromes did not modify
      the association of increasing use of guideline recommended medications and
      clinical outcomes. CONCLUSION: In older men with IHD, greater adherence to
      medication guidelines appears to be positively associated with better clinical
      outcomes, independent of geriatric syndromes.

PMID- 25988543
TI  - The Effect of Progressive-Tension Closure on Donor Site Seroma Formation in
      Delayed Latissimus Dorsi Flaps for Breast Reconstruction.
AB  - BACKGROUND: Autologous tissue flaps play an integral part in breast
      reconstruction. The latissimus dorsi myocutaneous flap is an effective and
      aesthetic method of immediate breast reconstruction, although a high rate of
      donor site seroma formation has plagued this procedure. Many techniques to reduce
      donor site seromas have been undertaken. This study evaluates the effect of
      progressive-tension closure (PTC) on postoperative seroma. METHODS: This is a
      retrospective cohort study of 100 breasts reconstructed using a traditional
      closure versus PTC of the donor site. Outcomes collected include patient age,
      date of surgery, side of surgery, body mass index (BMI), smoking status, diabetes
      diagnosis, number of days the initial operative drain was present, seroma
      occurrence, seroma aspirations, seroma catheters placed, and operative
      interventions. RESULTS: The PTC technique significantly decreased seroma
      formation, with 40% of the traditional closure sites developing seromas and only
      14% in the PTC group (P = 0.0078). The mean number of days the postoperative
      drain remained was significantly reduced with the PTC technique, just 16.6 days
      compared to 27.8 days (P < 0.0001). Of the seromas which did develop, the PTC
      group had significantly fewer aspirations (38.9% vs 14%, P = 0.014), drains
      placed (15.8% vs 4.6%, P < 0.0001), and operative interventions (7% vs 0%, P <
      0.0001). There was no significant difference in mean patient age (54.1, 52.4) or
      body mass index (28.1, 27.3) between the groups. CONCLUSIONS: The PTC technique
      of closing latissimus dorsi donor sites significantly decreases seroma formation,
      number of days a drain is present, and postoperative interventions. This
      decreases the time and resources devoted to addressing seromas.

PMID- 25988542
TI  - Pulsed light for the inactivation of fungal biofilms of clinically important
      pathogenic Candida species.
AB  - Microorganisms are naturally found as biofilm communities more than planktonic
      free-floating cells; however, planktonic culture remains the current model for
      microbiological studies, such as disinfection techniques. The presence of fungal
      biofilms in the clinical setting has a negative impact on patient mortality, as
      Candida biofilms have proved to be resistant to biocides in numerous in vitro
      studies; however, there is limited information on the effect of pulsed light on
      sessile communities. Here we report on the use of pulsed UV light for the
      effective inactivation of clinically relevant Candida species. Fungal biofilms
      were grown by use of a CDC reactor on clinically relevant surfaces. Following a
      maximal 72 h formation period, the densely populated biofilms were exposed to
      pulsed light at varying fluences to determine biofilm sensitivity to pulsed-light
      inactivation. The results were then compared to planktonic cell inactivation.
      High levels of inactivation of C. albicans and C. parapsilosis biofilms were
      achieved with pulsed light for both 48 and 72 h biofilm structures. The findings
      suggest that pulsed light has the potential to provide a means of surface
      decontamination, subsequently reducing the risk of infection to patients. The
      research described herein deals with an important aspect of disease prevention
      and public health. 

PMID- 25988544
TI  - Fusobacterium necrophorum and other Fusobacterium spp. isolated from head and
      neck infections: A 10-year epidemiology study in an academic hospital.
AB  - BACKGROUND: Fusobacterium spp. from clinical specimens are increasingly reported.
      We sought to describe the epidemiology, the microbiological, and the clinical
      characteristics of head and neck infections caused by Fusobacterium necrophorum
      and other Fusobacterium spp. MATERIALS AND METHODS: Retrospective cohort study
      between October 1st, 2004 and September 30(th), 2014 performed in an academic
      hospital. Electronic patient charts and the laboratory information system were
      reviewed for demographic and microbiological data. The number and percentages of
      specific diagnosis and treatment among patients with positive Fusobacterium spp.
      culture were calculated. The incidence was calculated based on the number of
      specimens investigated each year. RESULTS: Included were 230 cultures of 230
      patients (median age of 28 years, 61.7% men). F. necrophorum was often found in
      young patients with high C-reactive protein (CRP) and high number of leukocytes
      in blood. Other Fusobacterium spp. were often found in middle aged patients with
      relatively high CRP and slightly increased leukocytes. Three major causes of the
      isolation of F. necrophorum and other Fusobacterium spp. were acute tonsillitis
      (n = 18, incidence of 0.2%), peritonsillar abscess (n = 39, 0.5%) and acute
      otitis (n = 45, 0.1%). While F. necrophorum was found in majority (37/57) of
      patients with acute tonsillitis or peritonsillar abscess, Fusobacterium spp.
      other than F. necrophorum were found in the majority (35/45) of patients with
      acute otitis. Isolated fusobacteria were susceptible to beta-lactam antibiotics,
      clindamycin and metronidazole. The outcomes of patients with Fusobacterium spp.
      were good. CONCLUSION: F. necrophorum and other Fusobacterium spp. are rare cause
      of head and neck infections. The infections are well treated by combination of
      antibiotics and surgery.

PMID- 25988545
TI  - Pneumonia Outbreak Caused by Chlamydophila pneumoniae among US Air Force Academy
      Cadets, Colorado, USA.
AB  - During October 2013-May 2014, there were 102 cases of pneumonia diagnosed in US
      Air Force Academy cadets. A total of 73% of tested nasal washes contained
      Chlamydophila pneumoniae. This agent can be considered to be present on campus
      settings during outbreaks with numerous, seemingly disconnected cases of
      relatively mild pneumonia. 

PMID- 25988546
TI  - Spirochensilides A and B, Two New Rearranged Triterpenoids from Abies
      chensiensis.
AB  - Two new triterpenoids, spirochensilides A (1) and B (2) were isolated from Abies
      chensiensis. Comprehensive spectroscopic analysis revealed that 1 and 2 are the
      first example of triterpenoids possessing a unique 8,10-cyclo-9,10-seco and
      methyl-rearranged carbon skeleton. The single crystal X-ray diffraction analyses
      and computational methods allowed the absolute configuration assignments of the
      two compounds. A plausible biogenetic pathway of spirochensilide A (1) is also
      proposed. 

PMID- 25988547
TI  - Lipid droplet-organelle interactions: emerging roles in lipid metabolism.
AB  - Cellular homeostasis depends on the precisely coordinated use of lipids as fuels
      for energy production, building blocks for membrane biogenesis or chemical
      signals for intra-cellular and inter-cellular communication. Lipid droplets (LDs)
      are universally conserved dynamic organelles that can store and mobilize fatty
      acids and other lipid species for their multiple cellular roles. Increasing
      evidence suggests that contact zones between LDs and other organelles play
      important roles in the trafficking of lipids and in the regulation of lipid
      metabolism. Here we review recent advances regarding the nature and functional
      relevance of interactions between LDs and other organelles-particularly the
      endoplasmic reticulum (ER), LDs, mitochondria and vacuoles-that highlight their
      importance for lipid metabolism. 

PMID- 25988549
TI  - Endoscopic stenting for colorectal obstruction from unresectable ovarian and
      colorectal cancer: a bridge to surgery.

PMID- 25988551
TI  - Withdrawn: An unusual urticarial eruption: familial cold autoinflammatory
      syndrome.

PMID- 25988548
TI  - The essential roles of transition fibers in the context of cilia.
AB  - Once thought of as a vestigial organelle, the primary cilium is now recognized as
      a signaling hub for key cellular pathways in vertebrate development. The recent
      renaissance in cilia studies significantly improved our understanding of how
      cilia form and function, but little is known about how ciliogenesis is initiated
      and how ciliary proteins enter cilia. These important ciliary events require
      transition fibers (TFs) that are positioned at the ciliary base as symmetric nine
      bladed propeller fibrous structures. Up until recently, TFs have been the most
      underappreciated ciliary structures due to limited knowledge about their
      molecular composition and function. Here, we highlight recent advances in our
      understanding of TF composition and the indispensable roles of TFs in regulating
      the initiation of ciliogenesis and the selective import of ciliary proteins. 

PMID- 25988554
TI  - Prevalence of Eosinophilic Gastritis, Gastroenteritis, and Colitis: Estimates
      From a National Administrative Database.
AB  - OBJECTIVES: Eosinophilic esophagitis (EoE) is becoming increasingly more common,
      but the prevalence of other eosinophilic gastrointestinal disorders (EGIDs) is
      unknown. Our objective was to estimate the prevalence of eosinophilic gastritis,
      gastroenteritis, and colitis in the United States. METHODS: We used the IMS
      Health LifeLink PharMetrics Plus Claims Database, data representative of a US
      national commercially insured population containing medical and pharmaceutical
      claims for > 75 million individuals. We restricted our sample to patients ages 0
      to 64 with continuous enrollment between July 1, 2009, and June 30, 2011. We
      identified patients with eosinophilic gastritis, gastroenteritis, and colitis as
      defined by >= 1 instance of the International Classification of Diseases, Ninth
      Revision codes 535.70, 558.41, and 558.42, respectively. We calculated the
      prevalence of the codes in the database and then standardized the estimates to
      the US population by age and sex. RESULTS: The standardized estimated prevalences
      of eosinophilic gastritis, gastroenteritis, and colitis were 6.3/100,000,
      8.4/100,000, and 3.3/100,000, respectively. The prevalence of eosinophilic
      gastroenteritis was the highest among children age < 5 years, whereas
      eosinophilic gastritis was more prevalent among older age groups. We observed no
      age differences for eosinophilic colitis. Among affected patients, there was a
      high proportion of coexisting allergic conditions, 38.5% for eosinophilic
      gastritis, 45.6% for gastroenteritis, and 41.8% for colitis. Concomitant allergic
      disease was most commonly identified in pediatric patients. CONCLUSIONS: The
      prevalence of non-EoE EGIDs remains rare in the United States, with < 50,000
      total patients affected. There appears to be a female predominance and a high co
      occurrence of atopic comorbidities.

PMID- 25988553
TI  - Effects of Maternal Omega-3 Supplementation on Fatty Acids and on Visual and
      Cognitive Development.
AB  - OBJECTIVES: The aim of the present study was to elucidate whether a dairy drink
      enriched with omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) could have
      an impact on the lipid profile of the mother and the newborn, and also whether
      this intervention could affect the newborns' visual and cognitive development.
      METHODS: A total of 110 pregnant women were randomly assigned to one of the
      following intervention groups: control group (n = 54), taking 400 mL/day of the
      control dairy drink, and supplemented group (fish oil [FO]) (n = 56), taking 400
      mL/day of the fish oil-enriched dairy drink (including ~400 mg eicosapentaenoic
      acid-docosahexaenoic acid [DHA]/day). During the study, the mothers' diets were
      supervised by a nutritionist to encourage compliance with present recommendations
      of FA intake. Blood fatty acid profiles were determined in the mother's (at
      enrollment, at delivery, and at 2.5 and 4 months) and newborn (at delivery and at
      2.5 months) placenta and breast milk (colostrum and at 1, 2, and 4 months).
      Pattern reversal visual evoked potentials (VEPs) (at 2.5 and 7.5 months) and
      Bayley test (at 12 months) were recorded. RESULTS: DHA percentage was higher in
      plasma, erythrocyte membranes, and breast milk samples from the FO group. The
      ratio of nervonic acid was also higher in plasma and erythrocyte lipids of the
      mother and newborn's blood samples from the FO group. No differences were
      observed in the Bayley test. No differences were observed in VEPs between both
      groups. We observed a shorter latency, however, in the lower visual angle (7.5')
      in the boys of the supplemented group. CONCLUSIONS: Omega-3 LC-PUFA dietary
      supplement during pregnancy and lactation influenced the mother and newborn's
      fatty acid profile and nervonic acid content but did not show effects on visual
      and cognitive/psychomotor development.

PMID- 25988555
TI  - Electrolyte and Mineral Homeostasis After Optimizing Early Macronutrient Intakes
      in VLBW Infants on Parenteral Nutrition.
AB  - OBJECTIVES: The aim of the present study was to evaluate electrolyte and mineral
      homeostasis in very-low-birth-weight (VLBW) infants who received high protein and
      energy intakes with a unique standardized parenteral nutrition solution
      containing electrolytes and minerals from birth onward. METHODS: Prospective
      cohort study in 102 infants with birth weight <1250 g. The evolution of plasma
      biochemical parameters was described during the first 2 weeks of life. RESULTS:
      During the first 3 days of life, mean parenteral intakes were 51 +/- 8 kcal . kg
      . day with 2.7 +/- 0.4 g . kg . day of protein, 1.1 +/- 0.2 mmol . kg . day of
      sodium and potassium, and 1.3 +/- 0.2 mmol . kg . day of calcium and phosphorus.
      Afterwards, most nutritional intakes (parenteral and enteral) met growth
      requirements. No infant developed a hyperkalemia >7 mmol/L, and a hypernatremia
      >150 mmol/L occurred only in 15.7% of the infants. In contrast, hyponatremia <130
      mmol/L and hypokalemia <3 mmol/L occurred in 30.4% and 8.8% of the infants,
      respectively. The initial neonatal metabolic acidosis rapidly resolved in most
      infants and only 2.0% developed a base deficit >10 mmol/L after day 3 of life.
      Early hypocalcemia <1.8 mmol/L occurred in 13.7% of the infants. In contrast,
      hypophosphatemia <1.6 mmol/L occurred in 37.3% and hypercalcemia >2.8 mmol/L
      occurred in 12.7% of the infants. CONCLUSIONS: Increasing early protein and
      energy intakes in VLBW infants in the first week of life improves electrolyte
      homeostasis. It also increases the phosphorus requirements with a calcium-to
      phosphorus ratio <=1.0 (mmol/mmol) and the potassium and sodium requirements to
      avoid the development of a refeeding-like syndrome. These data suggest that the
      parenteral nutrition guidelines for VLBW infants for the first week of life need
      to be revised.

PMID- 25988556
TI  - Children With Anorectal Malformations, Hirschsprung Disease, and Their Siblings:
      Proxy Reports and Self-Reports.
AB  - OBJECTIVES: The aim of the present study was to compare parent proxy reports with
      that of self-reports of children with anorectal malformations (ARMs) or
      Hirschsprung disease (HD) and healthy siblings and thereafter was examine whether
      these comparisons differed between patients and their siblings. METHODS: Parents
      (n = 98) of either children with ARM (n = 44) or HD (n = 54) and a healthy
      sibling (n = 98) recruited from the 6 Dutch pediatric surgical centers and from
      the ARM and HD patient societies were included in this cross-sectional multilevel
      study. Agreement between child self-reports and parent proxy reports was compared
      through mean differences and through (intraclass) correlations. We conducted
      multilevel analyses to take dependencies between assessments within families into
      account. RESULTS: All of the children (children with ARM or HD and their
      siblings) reported more pain and symptoms than their parents reported. We also
      found that only children with ARM or HD reported less positive emotions than
      their parents. Furthermore, higher correlations were found between parent proxy
      reports and patient-self reports than between parent proxy reports and sibling
      self-reports on cognitive functioning and social interaction. CONCLUSIONS:
      Parents tend to overestimate the physical functioning of both their ill and
      healthy children, and overestimate the emotional functioning of only their
      children with ARM or HD. Furthermore, children with ARM or HD and parents agree
      more on health-related quality of life domains than healthy children and parents.

PMID- 25988557
TI  - Hepatitis D in Children.
AB  - Hepatitis D virus (HDV) is an uncommon, defective, single-stranded circular RNA
      virus that is dependent on the hepatitis B virus' surface antigen envelope
      proteins for transmission. It is highly pathogenic and associated with high rates
      of progression to cirrhosis and associated complications. HDV continues to ravage
      endemic parts of Asia and Europe, and its prevalence in the United States,
      although low, has not decreased in frequency, despite universal hepatitis B virus
      vaccination, because of lack of testing and underrecognition. There are few
      reports on the prevalence and characteristics of HDV infection in the pediatric
      population. We present 2 patients with HDV infection at our institution; both
      were from eastern Europe and were treated with pegylated interferon-alpha. The
      present standard of care treatment for HDV yields suboptimal results, but
      insights into the virology of hepatitis D are stimulating the search for novel
      therapeutic approaches, particularly the development of prenylation inhibitors
      and viral entry inhibitors. 

PMID- 25988558
TI  - Antecedent Predictors of Feeding Outcomes in Premature Infants With Protracted
      Mechanical Ventilation.
AB  - OBJECTIVES: The aim of the present study was to define risk factors associated
      with gastrostomy in premature infants receiving protracted mechanical ventilation
      (>=30 days). METHODS: Retrospective data collected on 170 preterm neonates (birth
      weight <1500 g) who received uninterrupted mechanical ventilation for >=30 days
      were analyzed with logistic regression methods to predict the association of
      gastrostomy with cardiorespiratory, infectious, and neurological morbidities.
      RESULTS: A total of 32 of 170 infants had gastrostomy tubes. Including all of the
      covariates in 1 model, duration of cumulative ventilation (P < 0.001) and
      uninterrupted ventilation (P < 0.001), and ventriculoperitoneal shunt (P = 0.02)
      were significant predictors, whereas sepsis, intraventrical hemorrhage grade III
      or IV, and patent ductus arteriosus ligation were not. Respiratory severity score
      (mean airway pressure * fraction of inspired oxygen) calculated at 30 days of
      life was also a significant predictor (P = 0.01). CONCLUSIONS: In infants with
      protracted mechanical ventilation, the degree of respiratory support at 1 month
      of age, prolonged respiratory morbidity, and neuropathology are the significant
      predictors for gastrostomy.

PMID- 25988559
TI  - Contribution of Esophagram to the Evaluation of Complicated Pediatric
      Eosinophilic Esophagitis.
AB  - OBJECTIVES: In contrast to peptic strictures, clinically significant strictures
      in patients with eosinophilic esophagitis (EoE) may be subtle and go unrecognized
      at the time of endoscopy. We aimed to identify how often stricture was identified
      by endoscopy as compared with contrast esophagram. METHODS: We retrospectively
      reviewed esophagram and endoscopy examinations of all of the patients with EoE
      with esophageal stricture seen at a tertiary care pediatric hospital over a 6
      year period who had both procedures completed within a 3-month time frame.
      Medical charts were reviewed for clinicopathologic information including age,
      duration of symptoms, histology, and treatment. RESULTS: Twenty-two children with
      EoE-associated stricture completed both esophagram and endoscopic assessments.
      Esophageal strictures were identified by esophagram, and not endoscopy, in 55% of
      these children. Patients with stricture identified at esophagram alone had a
      shorter duration of symptoms (2.1 years duration vs 5.4 years duration, P = 0.03)
      than the group identified by endoscopy. Preoperative radiographic identification
      of a stricture was associated with dilation more often being performed.
      CONCLUSIONS: Esophagram is a valuable test to assess esophageal anatomy in
      children with complicated EoE. Esophagram may be able to detect subtle
      fibrostenosis earlier in the natural history of the disease than endoscopy.

PMID- 25988560
TI  - Hepatitis B Virus Revaccination With Standard Versus Pre-S Vaccine in Previously
      Immunized Patients With Celiac Disease.
AB  - OBJECTIVE: Previous studies have suggested that hepatitis B virus (HBV) vaccines
      may be less immunogenic in individuals with celiac disease (CD). A pre-S vaccine
      (Sci-B-Vac) has demonstrated superior immunogenicity compared with standard HBV
      vaccines in several diseases. We compared the short-term immunogenicity of a pre
      S vaccine with a HBV vaccine (Engerix B) for repeat vaccination of seronegative,
      previously immunized patients with CD. METHODS: Participants were 1 to 18-year
      old children with CD who despite standard HBV vaccines in infancy had
      nonprotective hepatitis B surface antibody (HBs-Ab) concentrations (<=10 mIU/mL).
      Patients were randomized to receive either Engerix B or pre-S vaccine. HBs-Ab
      concentrations were measured 1 month after the first dose. For those who had not
      responded after 1 dose, measurement was repeated after the third dose. RESULTS:
      Children (n = 82) were analyzed (42 pre-S vaccine and 40 Engerix B). Baseline
      characteristics were similar for both groups, including gluten-free diet status.
      Both arms showed high response rates following the first injection: 41 (98%)
      versus 35 (87%) for pre-S vaccine and Engerix B recipients, respectively (P =
      0.08). All other patients responded when measured after dose 3. HBs-Ab
      concentrations (mIU/mL) were higher in the pre-S vaccine group (median 925,
      interquartile range [IQR] 424-1000) than the Engerix B group (median 363, IQR 106
      996, P = 0.005). Twenty (48%) of the pre-S vaccine recipients were "high
      responders" (>1000 mIU/mL) versus 10 (25%) in Engerix B recipients (P = 0.008).
      CONCLUSIONS: Both vaccines elicited adequate booster responses in most previously
      vaccinated patients with CD with nonprotective HBs-Ab concentrations. Pre-S
      vaccine administration resulted in higher Hbs-Ab concentrations. Our data suggest
      that a single dose of either vaccine is sufficient to raise titers to protective
      levels in most patients with CD.

PMID- 25988561
TI  - Short Sleep Duration Is Related to Emerging Cardiovascular Risk Factors in Obese
      Children.
AB  - OBJECTIVE: The aim of the present study was to evaluate the influence of sleep
      duration on cardiovascular risk factors in obese children. METHODS: Cross
      sectional analysis of 90 obese children ages 7 to 16 years. Anthropometric and
      clinical evaluation with specification of dietary and lifestyle habits was
      carried out during an office visit. Sleep duration was evaluated by the BEARS (B
      = bedtime issues, E = excessive daytime sleepiness, A = night awakening, R =
      regularity and duration of sleep, S = snoring) questionnaire on children's sleep
      characteristics. Sleep time adequacy by age was assessed according to the
      criteria of the National Sleep Foundation. Biochemical blood variables indicative
      of metabolic risk (glucose, lipid profile, and insulin) were obtained. Emergent
      new factors of metabolic risk, including high-sensitive C-reactive protein, gamma
      glutamyltranspeptidase, homocysteine, retinol-binding protein 4 (RBP4), thyroid
      stimulating hormone (TSH), inflammatory markers, and the adipokines leptin,
      adiponectin, and ghrelin were also evaluated. The relations between the duration
      of sleep and these variables were analyzed by general lineal model analysis.
      Significant variables were introduced in logistic regression analysis to
      determine the odds ratio (OR) and 95% confidence interval (CI) of cardiometabolic
      factors with respect to sleep. RESULTS: Children who slept for short duration
      were significantly more at risk of severe central obesity. In the regression
      model, the mean arterial pressure (odds ratio [OR] 1.10, 95% confidence interval
      [CI] 1.02-1.17, P = 0.008), homocysteine (OR 1.41, 95% CI 1.08-1.84, P = 0.013),
      RBP4 (OR 1.78, 95% CI 1.15-2.78, P = 0.010), and TSH (OR 2.01, 95% CI 1.21-3.34,
      P = 0.007) remain as significant independent predictors related to short sleep
      duration. We did not find any association between sleep duration and inflammatory
      markers or adipokines. CONCLUSIONS: Short sleep duration increases the severity
      of obesity and is related to cardiovascular risk factors in children.

PMID- 25988562
TI  - Omega-3 Fatty Acid-Rich Parenteral Nutrition: Is It a Double-Edged Sword?
AB  - Parenteral nutrition (PN) has been strongly associated with intestinal failure
      associated liver disease. Cholestasis, liver steatosis, and liver fibrosis are
      features of this liver injury, which can progress to end stage liver disease.
      Omega-3 fatty acid rich PN has been shown to alleviate cholestasis and steatosis.
      There have been reports although suggesting that it may not be able to arrest or
      reverse the progression to liver fibrosis. In this article, we develop a
      hypothesis of the mechanism of how Omega-3 fatty acid rich PN may influence the
      progression of fibrosis. 

PMID- 25988563
TI  - Death in Pediatric Intensive Care Unit: Not for Children With Acute Pancreatitis.

PMID- 25988564
TI  - Overuse of the Emergency Department and CT Scans in Pediatric IBD: Time for Hot
      Spotting?

PMID- 25988565
TI  - The Relationship Between Balance Confidence and Cognitive Motor Interference in
      Individuals With Multiple Sclerosis.
AB  - Gait and cognitive impairments are compounded when performed simultaneously in
      individuals with multiple sclerosis (MS), and this is termed cognitive-motor
      interference (CMI). The authors examined whether CMI is related to balance
      confidence in individuals with MS. They hypothesized that individuals with low
      balance confidence would exhibit greater CMI possibly indicating a behavioral
      modification during dual task conditions. Thirty-four individuals with MS
      completed Activity-specific Balance Confidence (ABC) scale and a cognitive
      assessment as well as single and dual task walking trials at a comfortable pace.
      CMI was calculated as the percent change in walking velocity and cognitive task
      performance from single- to dual-task conditions and termed dual-task cost (DTC).
      A correlation analysis was performed to determine the relationships between DTCs
      of gait and cognitive performance and ABC scores. The correlation analysis
      revealed no significant association between ABC and DTC of walking velocity (p >
      .05). A significant relationship between balance confidence and DTCs of cognition
      was observed. The observed relationships suggest individuals with MS tend to
      alter their cognitive performance rather than manipulating their gait when
      confronted with a dual task. Overall, the findings partially support a behavioral
      explanation of CMI in individuals with MS. 

PMID- 25988567
TI  - Sensitive, quantitative, and high-throughput detection of angiogenic markers
      using shape-coded hydrogel microparticles.
AB  - Elevated serum concentrations of angiogenic markers including vascular
      endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet
      derived growth factor (PDGF) have been correlated with various clinical disorders
      including cancer, cardiovascular diseases, diabetes mellitus, and liver fibrosis.
      In addition, the correlation between the serum concentrations of these factors,
      clinical diagnosis, prognosis, and response to therapeutic agents is significant.
      Thereby suggesting high-throughput detection of serum levels of angiogenic
      markers has important implications in early detection of different clinical
      disorders as well as for subsequent therapy monitoring. Here, we demonstrate the
      feasibility of utilization of shape-coded hydrogel microparticle based suspension
      arrays for quantitative and reproducible measurement of VEGF, FGF, and PDGF in
      single and multiplexed assays. Bio-inert PEG hydrogel attenuated the background
      signal thereby improving the sensitivity of the detection method as well as
      eliminating the need for blocking the proteins. In the singleplexed assay, the
      detection limits of 1.7 pg ml(-1), 1.4 pg ml(-1), and 1.5 pg ml(-1) for VEGF,
      FGF, and PDGF respectively indicated that the sensitivity of the developed method
      exceeds that of the conventional technologies. We also demonstrated that in the
      multiplexed assays, recovery of the proteins was within 20% of the expected
      values. The practical applicability of the hydrogel microparticle based detection
      system was established by demonstrating the ability of the system to quantify the
      production of VEGF, FGF, and PDGF by breast cancer cells (MDA-MB-231). 

PMID- 25988566
TI  - Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine
      Reveals Broad and Balanced Humoral Immunogenicity.
AB  - The current resurgence of whooping cough is alarming, and improved pertussis
      vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV)
      are potential vaccine candidates, but omvPV-induced humoral responses have not
      yet been characterized in detail. The purpose of this study was to determine the
      antigen composition of omvPV and to elucidate the immunogenicity of the
      individual antigens. Quantitative proteome analysis revealed the complex
      composition of omvPV. The omvPV immunogenicity profile in mice was compared to
      those of classic whole cell vaccine (wPV), acellular vaccine (aPV), and pertussis
      infection. Pertussis-specific antibody levels, antibody isotypes, IgG subclasses,
      and antigen specificity were determined after vaccination or infection by using a
      combination of multiplex immunoassays, two-dimensional immunoblotting, and mass
      spectrometry. The vaccines and infection raised strong antibody responses, but
      large quantitative and qualitative differences were measured. The highest
      antibody levels were obtained by omvPV. All IgG subclasses
      (IgG1/IgG2a/IgG2b/IgG3) were elicited by omvPV and in a lower magnitude by wPV,
      but not by aPV (IgG1) or infection (IgG2a/b). The majority of omvPV-induced
      antibodies were directed against Vag8, BrkA, and LPS. The broad and balanced
      humoral response makes omvPV a promising pertussis vaccine candidate. 

PMID- 25988568
TI  - Fatal false-negative transfusion infection involving a buffy coat platelet pool
      contaminated with biofilm-positive Staphylococcus epidermidis: a case report.
AB  - BACKGROUND: Bacterial contamination of platelet concentrates (PCs) poses the
      major posttransfusion infectious risk in developed countries. The aerobic
      microorganism most frequently isolated from PCs is coagulase-negative
      Staphylococcus epidermidis, a normal inhabitant of the human skin, which has been
      involved in fatal transfusion reactions worldwide. CASE REPORT: In September
      2014, a splenectomized elderly male patient, suffering from leukemia, was
      transfused with two 5-day-old buffy coat platelet (PLT) pools. The patient
      returned to emergency on the same day with a low-grade fever. He was bacteremic
      and died on the next day. Microbiology and molecular testing of a blood sample
      from the patient and one of the PCs yielded the same S. epidermidis strain.
      Further analysis demonstrated that this S. epidermidis isolate displays a biofilm
      positive phenotype in PCs. DISCUSSION: At Canadian Blood Services, PCs are
      screened for bacterial contamination with the BacT/ALERT system (bioMerieux) at
      approximately 24 hours postcollection. The implicated PC had been tested and
      yielded a false-negative culture result. A titration experiment indicated that,
      at the time of screening, the contaminated PC had a titer of less than 0.74
      colony-forming units (CFU)/mL (<227 CFUs/unit) of S. epidermidis. Mathematical
      models have predicted that up to 70% of PCs contaminated with coagulase-negative
      staphylococci at concentrations of 0.02 CFU/mL can be missed by BacT/ALERT
      screening. CONCLUSION: Despite several mitigation strategies, false-negative
      cultures with current PLT screening practices still occur. This report creates
      awareness of the pathogenicity of opportunistic S. epidermidis, a low-virulence
      organism, in susceptible patients who may not develop a typical transfusion
      reaction.

PMID- 25988571
TI  - Bonding Motifs of Noble-Gas Compounds As Described by the Local Electron Energy
      Density.
AB  - The bonding situation of some exemplary noble-gas (Ng) compounds, including
      HNg(+), HNgF, FNgO(-), Ng-HF, and NgBeO (Ng = He-Xe) was assayed by examining
      their local electron energy density H(r). In general, this function partitions
      the space of atomic species (neutral and ionic) into inner regions of negative
      values and outer regions of positive values. In the formation of chemical bonds,
      these atomic regions combine so to form a molecular H(r), Hmol(r), whose plotted
      form naturally shows the "covalent" and "noncovalent" regions of the molecular
      species and allows also the recognition of different types of noncovalent
      interactions such van der Waals, hydrogen, and ionic or partially ionic bonds.
      The qualitative assignment of the various bonding motifs is corroborated by the
      topological analysis of Hmol(r), which typically includes several critical points
      of rank 3 and variable signature. These points are, in particular, characterized
      here in terms of their bond degree (BD). From a previous definition (Espinosa J.
      Chem. Phys. 2002, 117, 5529-5542), this quantity is taken as the ratio between
      the energy density calculated at the critical point of H(r), H(rc), and the
      corresponding electron density rho(rc): BD = -H(rc)/rho(rc). Thus, the BD is
      positive for covalent interactions (H(rc) < 0) and negative for noncovalent
      interactions (H(rc) > 0). For structurally related species, the BD result, in
      general, positively correlated with the binding energies and is, therefore, a
      semiquantitative index of stability. The present study suggests the general
      validity of the Hmol(r) to effectively assay the bonding motifs of noble-gas
      compounds.

PMID- 25988570
TI  - Associations between dietary intake and the presence of the metabolic syndrome in
      patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Although dietary habits have been associated with the likelihood of
      the metabolic syndrome (MetS) in the general population, similar associations in
      non-alcoholic fatty liver disease (NAFLD) patients have not been explored. The
      aim of this cross-sectional study was to assess the presence of the MetS and to
      explore its potential association with dietary habits in a sample of NAFLD
      patients. METHODS: Seventy-three adult patients with recent NAFLD diagnosis based
      on elevated liver enzyme levels and evidence of hepatic steatosis on ultrasound
      were enrolled. Participants' habitual food consumption was retrospectively
      assessed through a food frequency questionnaire and adherence to the
      Mediterranean diet (MD) was assessed via the Mediterranean Diet Score
      (MedDietScore). The presence of the MetS was defined as the concomitant presence
      of at least three of its individual components, according to the criteria
      proposed by a recent joint statement of several major organisations. RESULTS: The
      MetS was present in 46.5% of the sample, with increased waist circumference
      values and decreased high-density lipoprotein cholesterol levels being the most
      prevalent disorders (63% and 88.7%, respectively). Consumption of refined grains
      [odds ratio (OR) = 1.02, 95% confidence interval (CI) = 1.00-1.05] and red meat
      and products (OR = 1.10, 95% CI = 1.01-1.21) were positively associated with the
      presence of the MetS, whereas the consumption of whole grains (OR = 0.92, 95% CI
      = 0.84-0.99) and MedDietScore (OR = 0.87, 95% CI = 0.76-0.99) were negatively
      associated, after adjusting for participants' age, sex, daily energy intake and
      time spent in sedentary activities. CONCLUSIONS: Low refined grain and red meat
      intake, high whole grain intake and high adherence to the MD were associated with
      lower odds of the MetS in NAFLD patients.

PMID- 25988569
TI  - Electroconductive Nanopatterned Substrates for Enhanced Myogenic Differentiation
      and Maturation.
AB  - Electrically conductive materials provide a suitable platform for the in vitro
      study of excitable cells, such as skeletal muscle cells, due to their inherent
      conductivity and electroactivity. Here it is demonstrated that bioinspired
      electroconductive nanopatterned substrates enhance myogenic differentiation and
      maturation. The topographical cues from the highly aligned collagen bundles that
      form the extracellular matrix of skeletal muscle tissue are mimicked using
      nanopatterns created with capillary force lithography. Electron beam deposition
      is then utilized to conformally coat nanopatterned substrates with a thin layer
      of either gold or titanium to create electroconductive substrates with well
      defined, large-area nanotopographical features. C2C12 cells, a myoblast cell
      line, are cultured for 7 d on substrates and the effects of topography and
      electrical conductivity on cellular morphology and myogenic differentiation are
      assessed. It is found that biomimetic nanotopography enhances the formation of
      aligned myotubes and the addition of an electroconductive coating promotes
      myogenic differentiation and maturation, as indicated by the upregulation of
      myogenic regulatory factors Myf5, MyoD, and myogenin (MyoG). These results
      suggest the suitability of electroconductive nanopatterned substrates as a
      biomimetic platform for the in vitro engineering of skeletal muscle tissue. 

PMID- 25988573
TI  - Derivation of normal diploid human embryonic stem cells from tripronuclear
      zygotes with analysis of their copy number variation and loss of heterozygosity.
AB  - This study sought to establish archives of genetic copy number variation (CNV) in
      human embryonic stem cell (hESC) lines that are associated with known diseases.
      We collected patients' fresh, discarded zygotes from in vitro fertilization (IVF)
      or intracytoplasmic sperm injection (ICSI) protocols. A total of 208 fresh,
      tripronuclear, discarded zygotes were also collected in this study from patients
      on the third day of their treatment cycle, prior to transfer. The blastula
      formation rates were 13.51% (26/192) and 26.7% (4/15) while the high-quality
      blastocyst formation rates were 5.8% (11/192) and 20% (3/15) in the IVF and ICSI
      groups, respectively. The inner cell mass (ICM) from each embryo was mechanically
      separated, and then grown on feeder layers consisting of mouse embryonic
      fibroblasts and human foreskin fibroblasts (a 1:1 mixture). The hESC karyotype
      was determined by traditional G-banding; analysis of the results for the Zh19P25
      and Zh20P24 cell lines showed that both were 46 XY. CNV and loss-of
      heterozygosity analysis of hESC gDNA was performed to assess the genetic
      characteristics associated with molecular diseases using the high-resolution
      Infinium High-Density HumanCytoSNP-12 DNA chip. Seven CNVs in Zh19P25 and Zh20P24
      were deletions, and a region that corresponds to Potocki-Shaffer disease, 11p11.2
      11p11.12 in Zh20P24, showed a 2.98-Mb loss. These data together suggest that
      single-nucleotide polymorphism (SNP) microarray analysis for molecular
      cytogenetic features can help to distinguish hESC lines with a normal karyotype
      from tripronuclear zygotes with known, disease-related characteristics.

PMID- 25988576
TI  - Having one's mate for dinner.

PMID- 25988574
TI  - Genome-wide site-specific differential methylation in the blood of individuals
      with Klinefelter syndrome.
AB  - Klinefelter syndrome (KS) (47 XXY) is a common sex-chromosome aneuploidy with an
      estimated prevalence of one in every 660 male births. Investigations into the
      associations between DNA methylation and the highly variable clinical
      manifestations of KS have largely focused on the supernumerary X chromosome;
      systematic investigations of the epigenome have been limited. We obtained genome
      wide DNA methylation data from peripheral blood using the Illumina
      HumanMethylation450K platform in 5 KS (47 XXY) versus 102 male (46 XY) and 113
      female (46 XX) control subjects participating in the COPDGene Study. Empirical
      Bayes-mediated models were used to test for differential methylation by KS
      status. CpG sites with a false-discovery rate < 0.05 in the discovery cohort
      which were available on the first-generation HumanMethylation 27 K platform were
      further examined in an independent replication cohort of 2 KS subjects, 590 male,
      and 495 female controls drawn from the International COPD Genetics Network
      (ICGN). Differential methylation at sites throughout the genome were identified,
      including 86 CpG sites that were differentially methylated in KS subjects
      relative to both male and female controls. CpG sites annotated to the HEN1
      methyltransferase homolog 1 (HENMT1), calcyclin-binding protein (CACYBP), and
      GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) genes were among
      the "KS-specific" loci that were replicated in ICGN. We conclude that site
      specific differential methylation exists throughout the genome in KS. The
      functional impact and clinical relevance of these differentially methylated loci
      should be explored in future studies.

PMID- 25988578
TI  - Rapidly Reversible Winging Scapula.

PMID- 25988579
TI  - Accumulation of contaminants of emerging concern in food crops-part 2: Plant
      distribution.
AB  - Arid agricultural regions often turn to using treated wastewater (reclaimed
      water) to irrigate food crops. Concerns arise, however, when considering the
      potential for persistent contaminants of emerging concern to accumulate into
      plants intended for human consumption. The present study examined the
      accumulation of a suite of 9 contaminants of emerging concern into 2
      representative food crops, lettuce and strawberry, following uptake via the roots
      and subsequent distribution to other plant tissues. Calculating accumulation
      metrics (concentration factors) allowed for comparison of the compartmental
      affinity of each chemical for each plant tissue compartment. The root
      concentration factor was found to exhibit a positive linear correlation with the
      pH-adjusted octanol-water partition coefficient (DOW ) for the target
      contaminants of emerging concern. Coupled with the concentration-dependent
      accumulation observed in the roots, this result implies that accumulation of
      these contaminants of emerging concern into plant roots is driven by passive
      partitioning. Of the contaminants of emerging concern examined, nonionizable
      contaminants, such as triclocarban, carbamazepine, and organophosphate flame
      retardants displayed the greatest potential for translocation from the roots to
      above-ground plant compartments. In particular, the organophosphate flame
      retardants displayed increasing affinity for shoots and fruits with decreasing
      size/octanol-water partition coefficient (KOW ). Cationic diphenhydramine and
      anionic sulfamethoxazole, once transported to the shoots of the strawberry plant,
      demonstrated the greatest potential of the contaminants examined to be then
      carried to the edible fruit portion.

PMID- 25988580
TI  - Pre-diagnostic cruciferous vegetables intake and lung cancer survival among
      Chinese women.
AB  - No study to date has prospectively evaluated the association between pre
      diagnostic cruciferous vegetables intake and lung cancer survival among women.
      This analysis included 547 incident lung cancer cases identified from the
      Shanghai Women's Health Study (SWHS) during the follow-up period of 1997-2011.
      Dietary intake was assessed for all SWHS participants at enrollment and
      reassessed 2-3 years later. Cox proportional hazards models were used to estimate
      hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for
      potential confounders. Of the 547 lung cancer patients, 412 patients died during
      the follow-up. A total of 393 (95.4%) deaths from lung cancer were documented
      with median survival time of 10.3 months (interquartile range, 3.6-21.1 months).
      High cruciferous vegetables intake was significantly associated with improved
      lung cancer-specific survival after adjusting for all nonclinical prognostic
      factors (n = 547, HR = 0.69; 95%CI = 0.49-0.95; P trend = 0.02) for the highest
      versus lowest quartile. A slightly stronger association of cruciferous vegetables
      intake with lung cancer-specific survival was observed in analyses restricted to
      patients with known clinical prognostic factors (n = 331, HR = 0.63; 95%CI = 0.41
      0.97; P trend = 0.03) or never smokers (n = 308, HR = 0.58; 95%CI = 0.37-0.91; P
      trend = 0.02). In conclusion, pre-diagnostic cruciferous vegetables intake is
      associated with better survival of lung cancer in Chinese women. 

PMID- 25988581
TI  - Fatal nosocomial MDR TB identified through routine genetic analysis and whole
      genome sequencing.

PMID- 25988582
TI  - SWEETs, transporters for intracellular and intercellular sugar translocation.
AB  - Three families of transporters have been identified as key players in
      intercellular transport of sugars: MSTs (monosaccharide transporters), SUTs
      (sucrose transporters) and SWEETs (hexose and sucrose transporters). MSTs and
      SUTs fall into the major facilitator superfamily; SWEETs constitute a
      structurally different class of transporters with only seven transmembrane
      spanning domains. The predicted topology of SWEETs is supported by crystal
      structures of bacterial homologs (SemiSWEETs). On average, angiosperm genomes
      contain ~20 paralogs, most of which serve distinct physiological roles. In
      Arabidopsis, AtSWEET8 and 13 feed the pollen; SWEET11 and 12 provide sucrose to
      the SUTs for phloem loading; AtSWEET11, 12 and 15 have distinct roles in seed
      filling; AtSWEET16 and 17 are vacuolar hexose transporters; and SWEET9 is
      essential for nectar secretion. The remaining family members await
      characterization, and could play roles in the gametophyte as well as other
      important roles in sugar transport in the plant. In rice and cassava, and
      possibly other systems, sucrose transporting SWEETs play central roles in
      pathogen resistance. Notably, the human genome also contains a glucose
      transporting isoform. Further analysis promises new insights into mechanism and
      regulation of assimilate allocation and a new potential for increasing crop
      yield. 

PMID- 25988583
TI  - Detection of monoclonality in intestinal lymphoma with polymerase chain reaction
      for antigen receptor gene rearrangement analysis to differentiate from enteritis
      in dogs.
AB  - The diagnosis of canine intestinal lymphoma by morphological examination is
      challenging, especially when endoscopic tissue specimens are used. The utility of
      detection of antigen receptor gene rearrangement by polymerase chain reaction
      (PARR) in canine lymphoma has been well established, but its usefulness to
      distinguish enteritis and intestinal lymphoma remains unclear. In this
      retrospective study we assessed clonality of 29 primary canine intestinal
      lymphoma, 14 enteritis and 15 healthy control cases by PARR analysis, using
      formalin-fixed, paraffin-embedded full-thickness tissue specimens. We could
      detect monoclonal rearrangements in 22 of 29 canine intestinal lymphomas [76%;
      95% confidence interval (CI) 56-90%] and polyclonal rearrangements in all of the
      enteritis and healthy control cases (100%; CI 88-100%). We revealed a
      predominance of T-cell phenotype compared to B-cell phenotype (85%; CI 65-96% and
      15%; CI 4-35%, respectively). We showed that PARR analysis contributes to
      differentiation of canine intestinal lymphoma from enteritis and to phenotyping
      of lymphomas.

PMID- 25988584
TI  - Transcription closed and open complex dynamics studies reveal balance between
      genetic determinants and co-factors.
AB  - In E. coli, promoter closed and open complexes are key steps in transcription
      initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis.
      However, the exact mechanism of initiation remains to be fully elucidated. Here,
      using single mRNA detection and dual reporter studies, we show that increased
      intracellular magnesium concentration affects Plac initiation complex formation
      resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates
      transcription transition, which modulates bimodality of mRNA distribution in the
      exponential phase. We reveal that Mg2+ regulates the size and frequency of the
      mRNA burst by changing the open complex duration. Moreover, increasing magnesium
      concentration leads to higher intrinsic and extrinsic noise in the exponential
      phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a
      shorter contact distance between aspartic acid residues and Nucleotide
      Triphosphate residues and increasing electrostatic charges in the active site.
      Our findings provide unique biophysical insights into the balanced mechanism of
      genetic determinants and magnesium ion in transcription initiation regulation
      during cell growth.

PMID- 25988586
TI  - Interface Trap Density Reduction for Al2O3/GaN (0001) Interfaces by Oxidizing
      Surface Preparation prior to Atomic Layer Deposition.
AB  - We correlate interfacial defect state densities with the chemical composition of
      the Al2O3/GaN interface in metal-oxide-semiconductor (MOS) structures using
      synchrotron photoelectron emission spectroscopy (PES), cathodoluminescence and
      high-temperature capacitance-voltage measurements. The influence of the wet
      chemical pretreatments involving (1) HCl+HF etching or (2) NH4OH(aq) exposure
      prior to atomic layer deposition (ALD) of Al2O3 were investigated on n-type GaN
      (0001) substrates. Prior to ALD, PES analysis of the NH4OH(aq) treated surface
      shows a greater Ga2O3 component compared to either HCl+HF treated or as-received
      surfaces. The lowest surface concentration of oxygen species is detected on the
      acid etched surface, whereas the NH4OH treated sample reveals the lowest carbon
      surface concentration. Both surface pretreatments improve electrical
      characteristics of MOS capacitors compared to untreated samples by reducing the
      Al2O3/GaN interface state density. The lowest interfacial trap density at
      energies in the upper band gap is detected for samples pretreated with NH4OH.
      These results are consistent with cathodoluminescence data indicating that the
      NH4OH treated samples show the strongest band edge emission compared to as
      received and acid etched samples. PES results indicate that the combination of
      reduced carbon contamination while maintaining a Ga2O3 interfacial layer by
      NH4OH(aq) exposure prior to ALD results in fewer interface traps after Al2O3
      deposition on the GaN substrate. 

PMID- 25988585
TI  - Typology of alcohol mixed with energy drink consumers: motivations for use.
AB  - BACKGROUND: Previous research on alcohol mixed with energy drinks (AmED) has
      shown that use is typically driven by hedonistic, social, functional, and
      intoxication-related motives, with differential associations with alcohol-related
      harm across these constructs. There has been no research looking at whether there
      are subgroups of consumers based on patterns of motivations. Consequently, the
      aims were to determine the typology of motivations for AmED use among a community
      sample and to identify correlates of subgroup membership. In addition, we aimed
      to determine whether this structure of motivations applied to a university
      student sample. METHODS: Data were used from an Australian community sample (n =
      731) and an Australian university student sample (n = 594) who were identified as
      AmED consumers when completing an online survey about their alcohol and ED use.
      Participants reported their level of agreement with 14 motivations for AmED use;
      latent classes of AmED consumers were identified based on patterns of motivation
      endorsement using latent class analysis. RESULTS: A 4-class model was selected
      using data from the community sample: (i) taste consumers (31%): endorsed
      pleasurable taste; (ii) energy-seeking consumers (24%): endorsed functional and
      taste motives; (iii) hedonistic consumers (33%): endorse pleasure and sensation
      seeking motives, as well as functional and taste motives; and (iv) intoxication
      related consumers (12%): endorsed motives related to feeling in control of
      intoxication, as well as hedonistic, functional, and taste motives. The consumer
      subgroups typically did not differ on demographics, other drug use, alcohol and
      ED use, and AmED risk taking. The patterns of motivations for the 4-class model
      were similar for the university student sample. CONCLUSIONS: This study indicated
      the existence of 4 subgroups of AmED consumers based on their patterns of
      motivations for AmED use consistently structured across the community and
      university student sample. These findings lend support to the growing
      conceptualization of AmED consumers as a heterogeneous group in regard to
      motivations for use, with a hierarchical and cumulative class order in regard to
      the number of types of motivation for AmED use. Prospective research may endeavor
      to link session-specific motives and outcomes, as it is apparent that primary
      consumption motives may be fluid between sessions.

PMID- 25988587
TI  - Tobacco use and dental myths In India: need for specific intervention.

PMID- 25988588
TI  - Overcoming birth weight: can physical activity mitigate birth weight-related
      differences in adiposity?
AB  - BACKGROUND: Individuals born at low or high birth weight (BW) have elevated
      adiposity. The extent to which physical activity can mitigate this risk is
      unknown. OBJECTIVES: The aim of this study was to determine if associations
      between BW and adiposity vary by self-reported moderate-to-vigorous physical
      activity (MVPA) among adolescents. METHODS: We used data on adolescents in the
      National Health and Nutrition Examination Survey (1999-2006; 12-15 years; n =
      4064). Using gender-stratified linear regression, we modelled body mass index
      (BMI) and waist circumference (WC) z-scores as a function of low, normal and high
      BW, MVPA (weekly Metabolic Equivalent of Task hours) and MVPA*BW cross-product
      terms, adjusting for sociodemographics, diet and, in WC models, BMI. RESULTS:
      Among girls with low MVPA, those born with high BW had greater BMI than normal
      BW; this difference diminished with greater MVPA (coefficient [95% confidence
      interval]: low MVPA: 0.72 [0.29, 1.14]; high MVPA: -0.04 [-0.48, 0.39]; P for
      interaction = 0.05). Among boys, MVPA did not modify the associations between BW
      and BMI. WC was unrelated to BW, regardless of MVPA. CONCLUSIONS: Findings
      suggest that effects of high BW in total adiposity can be more easily modified
      with MVPA in adolescent girls than in boys.

PMID- 25988590
TI  - Impact of Mutating the Key Residues of a Bifunctional 5,10
      Methylenetetrahydrofolate Dehydrogenase-Cyclohydrolase from Escherichia coli on
      Its Activities.
AB  - Methylenetetrahydrofolate dehydrogenase-cyclohydrolase (FolD) catalyzes
      interconversion of 5,10-methylene-tetrahydrofolate and 10-formyl-tetrahydrofolate
      in the one-carbon metabolic pathway. In some organisms, the essential requirement
      of 10-formyl-tetrahydrofolate may also be fulfilled by formyltetrahydrofolate
      synthetase (Fhs). Recently, we developed an Escherichia coli strain in which the
      folD gene was deleted in the presence of Clostridium perfringens fhs (E. coli
      DeltafolD/p-fhs) and used it to purify FolD mutants (free from the host-encoded
      FolD) and determine their biological activities. Mutations in the key residues of
      E. coli FolD, as identified from three-dimensional structures (D121A, Q98K, K54S,
      Y50S, and R191E), and a genetic screen (G122D and C58Y) were generated, and the
      mutant proteins were purified to determine their kinetic constants. Except for
      the R191E and K54S mutants, others were highly compromised in terms of both
      dehydrogenase and cyclohydrolase activities. While the R191E mutant showed high
      cyclohydrolase activity, it retained only a residual dehydrogenase activity. On
      the other hand, the K54S mutant lacked the cyclohydrolase activity but possessed
      high dehydrogenase activity. The D121A and G122D (in a loop between two helices)
      mutants were highly compromised in terms of both dehydrogenase and cyclohydrolase
      activities. In vivo and in vitro characterization of wild-type and mutant (R191E,
      G122D, D121A, Q98K, C58Y, K54S, and Y50S) FolD together with three-dimensional
      modeling has allowed us to develop a better understanding of the mechanism for
      substrate binding and catalysis by E. coli FolD. 

PMID- 25988589
TI  - The effectiveness of brief alcohol interventions delivered by community
      pharmacists: randomized controlled trial.
AB  - BACKGROUND AND AIMS: To undertake the first randomized controlled trial to
      evaluate the effectiveness of a brief intervention delivered by community
      pharmacists to reduce hazardous or harmful drinking. DESIGN: This parallel group
      randomized trial allocated participants individually to brief alcohol
      intervention (n = 205) or a leaflet-only control condition (n = 202), with follow
      up study after 3 months. SETTING: Sixteen community pharmacies in one London
      Borough, UK. PARTICIPANTS: A total of 407 pharmacy customers (aged 18 years or
      over) with Alcohol Use Disorder Identification Test (AUDIT) scores 8-19,
      inclusive. INTERVENTION: A brief motivational discussion of approximately 10
      minutes' duration, for which 17 pharmacists received a half-day of training.
      MEASUREMENTS: Hazardous or harmful drinking was assessed using the AUDIT
      administered by telephone by a researcher blind to allocation status. The two
      primary outcomes were: (1) change in AUDIT total scores and (2) the proportions
      no longer hazardous or harmful drinkers (scoring < 8) at 3 months. The four
      secondary outcomes were: the three subscale scores of the AUDIT (for consumption,
      problems and dependence) and health status according to the EQ-5D (a standardized
      instrument for use as a measure of health outcome). FINDINGS: At 3 months 326
      (80% overall; 82% intervention, 78% control) participants were followed-up. The
      difference in reduction in total AUDIT score (intervention minus control) was 
      0.57, 95% confidence interval (CI) = -1.59 to 0.45, P = 0.28. The odds ratio for
      AUDIT ? 8 (control as reference) was 0.87, 95% CI = 0.50 to 1.51, P = 0.61). For
      two of the four secondary outcomes (dependence score: -0.46, 95% CI = -0.82 to 
      0.09, P = 0.014; health status score: -0.09, 95% CI = -0.16 to -0.02, P = 0.013)
      the control group did better, and in the other two there were no differences
      (consumption score: -0.05, 95% CI = -0.54 to 0.44, P = 0.85; non-dependence
      problems score: -0.13, 95% CI = -0.66 to 0.41). Sensitivity analyses did not
      change these findings. CONCLUSIONS: A brief intervention delivered by community
      pharmacists appears to have had no effect in reducing hazardous or harmful
      alcohol consumption.

PMID- 25988591
TI  - Three temperature regimes in superconducting photon detectors: quantum, thermal
      and multiple phase-slips as generators of dark counts.
AB  - We perform measurements of the switching current distributions of three w ~ 120
      nm wide, 4 nm thick NbN superconducting strips which are used for single-photon
      detectors. These strips are much wider than the diameter of the vortex cores, so
      they are classified as quasi-two-dimensional (quasi-2D). We discover evidence of
      macroscopic quantum tunneling by observing the saturation of the standard
      deviation of the switching distributions at temperatures around 2 K. We analyze
      our results using the Kurkijarvi-Garg model and find that the escape temperature
      also saturates at low temperatures, confirming that at sufficiently low
      temperatures, macroscopic quantum tunneling is possible in quasi-2D strips and
      can contribute to dark counts observed in single photon detectors. At the highest
      temperatures the system enters a multiple phase-slip regime. In this range single
      phase-slips are unable to produce dark counts and the fluctuations in the
      switching current are reduced. 

PMID- 25988593
TI  - 'Because That's the Way It's Always Been Done': Reviewing the Nurse-Initiated
      Rules in a Mental Health Unit as a Step Toward Trauma-Informed Care.
AB  - Acknowledgement of the effects of trauma in the lives of the mental health
      service user population is increasingly being recognised as an imperative for
      Mental Health services. 'Trauma-informed care' provides values to guide practice.
      Mental Health nurses are well placed to commence integrating trauma-informed care
      into everyday practice. This paper describes the process of reviewing the nurse
      led rules in an acute inpatient mental health unit as one step toward providing a
      trauma-informed environment. Findings from questionnaires are used to highlight
      the applicability of the process to the underlying values of trauma-informed
      care. Consistency and transparency of rules is demonstrated as a nursing-led step
      toward establishing emotional safety and creating a trauma-informed environment. 

PMID- 25988592
TI  - Exposure to a youthful circulaton rejuvenates bone repair through modulation of
      beta-catenin.
AB  - The capacity for tissues to repair and regenerate diminishes with age. We sought
      to determine the age-dependent contribution of native mesenchymal cells and
      circulating factors on in vivo bone repair. Here we show that exposure to
      youthful circulation by heterochronic parabiosis reverses the aged fracture
      repair phenotype and the diminished osteoblastic differentiation capacity of old
      animals. This rejuvenation effect is recapitulated by engraftment of young
      haematopoietic cells into old animals. During rejuvenation, beta-catenin
      signalling, a pathway important in osteoblast differentiation, is modulated in
      the early repair process and required for rejuvenation of the aged phenotype.
      Temporal reduction of beta-catenin signalling during early fracture repair
      improves bone healing in old mice. Our data indicate that young haematopoietic
      cells have the capacity to rejuvenate bone repair and this is mediated at least
      in part through beta-catenin, raising the possibility that agents that modulate
      beta-catenin can improve the pace or quality of fracture repair in the ageing
      population. 

PMID- 25988594
TI  - A qualitative study of nurses' clinical experience in recognising low mood and
      depression in older patients with multiple long-term conditions.
AB  - AIMS AND OBJECTIVES: To explore how nurses' recognise depression in older
      patients with multiple long-term conditions and the strategies they use to
      support the patient. BACKGROUND: Depression decreases an older person's quality
      of life and sense of wellness, and increases functional impairment. The positive
      role of nurses working with patients with long-term conditions is now being
      recognised internationally; however, there is a gap in the research about how
      nurses recognise depression in older patients and how this impacts on their
      practice. DESIGN: This is a qualitative study informed by a constructivist
      grounded theory approach. METHODS: In-depth telephone interviews were conducted
      with 40 nurses working in geographically diverse areas in New Zealand. RESULTS:
      Having the conversation with older patients about their low moods, or
      specifically about depression was not something that all the nurses had, or felt
      they could have. While some nurses knew they could provide specific advice to
      patients, others believed this was not their responsibility, or within the scope
      of their role. CONCLUSION: Faced with an increasing number of older people with
      long-term conditions, one of which maybe depression itself or as a result of
      living with other long-term conditions, ongoing monitoring and support pathways
      are necessary to prevent further decline in the older person's quality of life
      and well-being. RELEVANCE TO CLINICAL PRACTICE: Nurses in primary health care can
      build on current knowledge and skills to increase their capability to promote
      'ageing well' with older people who have long-term conditions and depression.

PMID- 25988596
TI  - Ultrasensitive DNA sensor based on gold nanoparticles/reduced graphene
      oxide/glassy carbon electrode.
AB  - We have designed a simple and novel electrochemical biosensor based on glassy
      carbon electrode (GCE) for DNA detection. GCE was modified with reduced graphene
      oxide (RGO) and gold nanoparticles (AuNPs) by the electrochemical method, which
      is helpful for immobilization of thiolated bioreceptors. The electrode
      modification processes were characterized by scanning electron microscopy (SEM)
      and electrochemical methods. Then a single-stranded DNA (ssDNA) probe for BRCA1
      5382 insC mutation detection was immobilized on the modified electrode for a
      specific time. The experimental conditions, such as probe immobilization time and
      target DNA (complementary DNA) hybridization time and temperature with probe DNA,
      were optimized using electrochemical methods. The electrochemical response for
      DNA hybridization and synthesis was measured using electrochemical impedance
      spectroscopy (EIS) and cyclic voltammetry (CV) methods. The calibration graph
      contains two linear ranges; the first part is in the range of 3.0*10(-20) to
      1.0*10(-12)M, and the second segment part is in the range of 1.0*10(-12) to
      1.0*10(-7)M. The biosensor showed excellent selectivity for the detection of the
      complementary sequences from noncomplementary sequences, so it can be used for
      detection of breast cancer. 

PMID- 25988595
TI  - Prolyl hydroxylase inhibition corrects functional iron deficiency and
      inflammation-induced anaemia in rats.
AB  - BACKGROUND AND PURPOSE: Small-molecule inhibitors of prolyl hydroxylase (PHD)
      enzymes are a novel target for the treatment of anaemia and functional iron
      deficiency (FID). Other than being orally bioavailable, the differentiation of
      PHD inhibitors from recombinant human erythropoietin (rhEPO) has not been
      demonstrated. EXPERIMENTAL APPROACH: JNJ-42905343 was identified and
      characterized as a novel inhibitor of PHD and its action was compared with rhEPO
      in healthy rats and in a rat model of inflammation-induced anaemia and FID
      [peptidoglycan-polysaccharide (PGPS) model]. KEY RESULTS: Oral administration of
      JNJ-42905343 to healthy rats increased the gene expression of cytochrome b
      (DcytB) and divalent metal-ion transporter 1 (DMT1) in the duodenum, and
      increased plasma EPO. Repeated administration of JNJ-42905343 for 28 days
      increased blood haemoglobin, mean corpuscular haemoglobin (MCH) and mean
      corpuscular volume (MCV). The serum iron concentration was increased with low
      doses (0.3 mg.kg(-1) ) but reduced at high doses (6 mg.kg(-1) ). In PGPS-treated
      rats, administration of JNJ-42905343 for 28 days corrected FID and anaemia, as
      reflected by increased blood haemoglobin, MCH and MCV. Increased expression of
      DcytB and DMT1 genes in the duodenum resulting in increased iron availability was
      defined as the mechanism for these effects. rhEPO did not affect DcytB and DMT1
      and was not effective in PGPS-treated rats. CONCLUSIONS AND IMPLICATIONS: PHD
      inhibition has a beneficial effect on iron metabolism in addition to stimulating
      the release of EPO. Small-molecule inhibitors of PHD such as JNJ-42905343
      represent a mechanism distinct from rhEPO to treat anaemia and FID.

PMID- 25988597
TI  - Electrostatically Reversible Polarity of Ambipolar alpha-MoTe2 Transistors.
AB  - A doping-free transistor made of ambipolar alpha-phase molybdenum ditelluride
      (alpha-MoTe2) is proposed in which the transistor polarity (p-type and n-type) is
      electrostatically controlled by dual top gates. The voltage signal in one of the
      gates determines the transistor polarity, while the other gate modulates the
      drain current. We demonstrate the transistor operation experimentally, with
      electrostatically controlled polarity of both p- and n-type in a single
      transistor. 

PMID- 25988598
TI  - Use of three-dimensional printed 'haptic' models for preoperative planning in an
      Australian plastic surgery unit.

PMID- 25988599
TI  - Direct laser-writing of ferroelectric single-crystal waveguide architectures in
      glass for 3D integrated optics.
AB  - Direct three-dimensional laser writing of amorphous waveguides inside glass has
      been studied intensely as an attractive route for fabricating photonic integrated
      circuits. However, achieving essential nonlinear-optic functionality in such
      devices will also require the ability to create high-quality single-crystal
      waveguides. Femtosecond laser irradiation is capable of crystallizing glass in
      3D, but producing optical-quality single-crystal structures suitable for
      waveguiding poses unique challenges that are unprecedented in the field of
      crystal growth. In this work, we use a high angular-resolution electron
      diffraction method to obtain the first conclusive confirmation that uniform
      single crystals can be grown inside glass by femtosecond laser writing under
      optimized conditions. We confirm waveguiding capability and present the first
      quantitative measurement of power transmission through a laser-written crystal-in
      glass waveguide, yielding loss of 2.64 dB/cm at 1530 nm. We demonstrate
      uniformity of the crystal cross-section down the length of the waveguide and
      quantify its birefringence. Finally, as a proof-of-concept for patterning more
      complex device geometries, we demonstrate the use of dynamic phase modulation to
      grow symmetric crystal junctions with single-pass writing. 

PMID- 25988600
TI  - Asymmetrical allocation of JAK1 mRNA during spermatogonial stem cell division in
      Xenopus laevis.
AB  - During Xenopus spermatogenesis, each primary spermatogonium (PG), the largest
      single cell in the testis, undergoes mitotic divisions with a concomitant
      decrease in size to produce smaller differentiating spermatogonia. The
      spermatogonial stem cells (SSCs) occur in this PG population. Taking advantage of
      identifiable and isolatable properties of Xenopus SSCs, we examined JAK1 gene
      expression during the spermatogenesis because there have been reports on the
      important role of JAK/STAT pathway in regulating the status of SSCs in Drosophila
      and mouse. Surprisingly, in situ hybridization revealed the presence of JAK1 mRNA
      in the differentiating spermatogonia and primary spermatocytes as well as some
      PGs. Inhibition of JAK1 activity in the testis caused a decrease in percentage of
      BrdU-incorporating spermatogonia, suggesting that JAK1 was at least involved in
      regulation of spermatogonial proliferation. Interestingly, single cell reverse
      transcription-polymerase chain reaction (RT-PCR) clearly showed two different
      types of SSCs: SSCs with JAK1 mRNA (JAK1+ ) or without JAK1 mRNA (JAK1- ). Since
      JAK1- SSC level was increased by induction of testis regeneration, self-renewing
      SSCs were thought to be JAK1- . In addition, we found barrel-shaped PGs, in which
      JAK1 mRNA was localized asymmetrically to one half of the cell. The stainability
      with propidium iodide and morphology of two nuclei in the barrel-shaped PG were
      similar to those of PG nucleus. Based on the above observations, we propose the
      hypothesis that JAK1+ SSC is preparing for production of PGs destined to
      differentiate (destined PGs) and the accumulated JAK1 mRNA in the SSC is
      distributed exclusively into the destined PGs through mitotic division.

PMID- 25988601
TI  - Selective use of transradial access for endovascular treatment of severe
      intracranial vertebrobasilar artery stenosis.
AB  - OBJECTIVE: To study the feasibility and safety of transradial artery access for
      endovascular intervention of severe intracranial vertebrobasilar stenosis for
      selected patients not suitable for transfemoral access. METHODS: This was a
      retrospective analysis of 58 patients who had undergone intervention for severe
      intracranial vertebrobasilar stenosis using transradial access between January
      2012 and September 2014. The reasons for transradial access were traced. The
      outcome measures were the technical success rate, 30-day stroke or death in the
      territory of the culprit artery, periprocedural and access site complication
      rates. RESULTS: Out of the 58 patients, 19 patients (32.8%) used the transradial
      approach due to poor iliofemoral artery access, 28 (48.3%) due to unfavorable
      brachiocephalic or subclavian artery anatomy, 11 (19%) due to unfavorable
      vertebral artery anatomy. The technical success rate was 100%. There were four
      periprocedural complications, one of which was asymptomatic. The 30-day stroke
      rate was 5.2% (3/58 patients), with two of them having no residual neurological
      deficits. There was no mortality. None had access site complications.
      CONCLUSIONS: For selected patients with severe intracranial vertebrobasilar
      stenosis with difficult femoral access or anatomical variations precluding
      provision of a stable support for intracranial intervention, the transradial
      approach was shown to be a safe and feasible alternative route of access. Future
      trials of endovascular treatment for intracranial posterior circulation strokes
      should take into account the route of access.

PMID- 25988602
TI  - To operate or not?: A literature review of surgical outcomes in 95 patients with
      Parkinson's disease undergoing spine surgery.
AB  - INTRODUCTION: Degenerative spondylosis and kyphoscoliosis are increasingly
      recognized entities in patients with Parkinson's disease. Surgical treatment with
      spinal fusion can be complicated due to poor bone quality and muscular
      dysfunction in this patient population. The goal of this paper is to investigate
      surgical outcomes in Parkinson's patients undergoing spine surgery. METHODS: We
      performed a literature review using the PubMed and Google Scholar search engines
      investigating "Parkinson's disease and spinal fusion surgery" from the period of
      2000 to 2013. The inclusion criteria included only English articles with
      Parkinson's patients that underwent spinal surgery. We identified and reviewed
      all six articles that included ninety-five patients with Parkinson's disease who
      underwent spinal surgery. RESULTS: A total of 95 patients with Parkinson's
      disease who underwent spinal fusion surgery were reviewed with average patient
      age of 69 and a 3:4 male to female ratio. With an average follow up of 40 months,
      46 out of 73 patients (63%) were judged to have satisfactory outcomes with poor
      outcomes noted in the remaining 37%. These included but were not limited to
      pseudoarthrosis, hardware failure/pullout, development of adjacent level disease,
      persistent kyphosis or sagittal imbalance, and no improvement or worsening in
      their postoperative visual analog pain scale. There was a 45% (29/65) revision
      rate and a 59% (30/51) complication rate following the index procedure.
      CONCLUSION: It remains unclear whether Parkinson's patients benefit from spinal
      fusion surgery. Further prospective research is warranted to investigate surgical
      outcomes in this subset of patients.

PMID- 25988603
TI  - A possible variant of negative motor seizure arising from the supplementary
      negative motor area.

PMID- 25988604
TI  - Publication bias in meta-analyses from the Cochrane Database of Systematic
      Reviews.
AB  - We used a Bayesian hierarchical selection model to study publication bias in 1106
      meta-analyses from the Cochrane Database of Systematic Reviews comparing
      treatment with either placebo or no treatment. For meta-analyses of efficacy, we
      estimated the ratio of the probability of including statistically significant
      outcomes favoring treatment to the probability of including other outcomes. For
      meta-analyses of safety, we estimated the ratio of the probability of including
      results showing no evidence of adverse effects to the probability of including
      results demonstrating the presence of adverse effects. RESULTS: In the meta
      analyses of efficacy, outcomes favoring treatment had on average a 27% (95%
      Credible Interval (CI): 18% to 36%) higher probability to be included than other
      outcomes. In the meta-analyses of safety, results showing no evidence of adverse
      effects were on average 78% (95% CI: 51% to 113%) more likely to be included than
      results demonstrating that adverse effects existed. In general, the amount of
      over-representation of findings favorable to treatment was larger in meta
      analyses including older studies. CONCLUSIONS: In the largest study on
      publication bias in meta-analyses to date, we found evidence of publication bias
      in Cochrane systematic reviews. In general, publication bias is smaller in meta
      analyses of more recent studies, indicating their better reliability and
      supporting the effectiveness of the measures used to reduce publication bias in
      clinical trials. Our results indicate the need to apply currently underutilized
      meta-analysis tools handling publication bias based on the statistical
      significance, especially when studies included in a meta-analysis are not recent.

PMID- 25988605
TI  - Investigating endocrine and physiological parameters of captive American kestrels
      exposed by diet to selected organophosphate flame retardants.
AB  - Organophosphate triesters are high production volume additive flame retardants
      (OPFRs) and plasticizers. Shown to accumulate in abiotic and biotic environmental
      compartments, little is known about the risks they pose. Captive adult male
      American kestrels (Falco sparverius) were fed the same dose (22 ng OPFR/g
      kestrel/d) daily (21 d) of tris(2-butoxyethyl) phosphate (TBOEP), tris(2
      chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), or
      tris(1,2-dichloro-2-propyl) phosphate (TDCIPP). Concentrations were undetected in
      tissues (renal, hepatic), suggesting rapid metabolism. There were no changes in
      glutathione status, indicators of hepatic oxidative status, or the cholinergic
      system (i.e., cerebrum, plasma cholinesterases; cerebrum muscarinic, nicotinic
      receptors). Modest changes occurred in hepatocyte integrity and function
      (clinical chemistry). Significant effects on plasma free triiodothyronine (FT3)
      concentrations occurred with exposure to TBOEP, TCEP, TCIPP, and TDCIPP; TBOEP
      and TCEP had additional overall effects on free thyroxine (FT4), whereas TDCIPP
      also influenced total thyroxine (TT4). Relative increases (32%-96%) in
      circulating FT3, TT3, FT4, and/or TT4 were variable with each OPFR at 7 d
      exposure, but limited thereafter, which was likely maintained through decreased
      thyroid gland activity and increased hepatic deiodinase activity. The observed
      physiological and endocrine effects occurred at environmentally relevant
      concentrations and suggest parent OPFRs or metabolites may have been present
      despite rapid degradation.

PMID- 25988606
TI  - A first-principles study of the electronic structure and mechanical and optical
      properties of CaAlSiN3.
AB  - The mechanical properties, electronic structures and optical properties of
      CaAlSiN3 were investigated using the first-principles calculations. The elastic
      constants, bulk moduli, shear moduli, Young's moduli, and Poisson's ratio were
      obtained. These results indicate that CaAlSiN3 is mechanically stable and a
      relatively hard material. Moreover, this compound has an indirect band gap of
      ~3.4 eV according to its band structure and density of states. The linear photon
      energy dependent dielectric functions and related optical properties including
      the refractive index, extinction coefficient, absorption spectrum, reflectivity,
      and energy loss spectrum were computed and discussed. It is shown that no sizable
      anisotropy is found in the optical properties of CaAlSiN3. The obtained
      structural estimation and some other results are in agreement with available
      experimental and theoretical data. This investigation is not only helpful for
      better understanding the electronic, mechanical and optical properties of
      CaAlSiN3, but also will open up the possibility of its use in device
      applications. 

PMID- 25988607
TI  - Porous hollow carbon spheres decorated with molybdenum diselenide nanosheets as
      anodes for highly reversible lithium and sodium storage.
AB  - Porous hollow carbon spheres (PHCS) decorated with MoSe2 nanosheets (MoSe2@ PHCS)
      are synthesized via a three-step process. Uniform and conformal MoSe2 nanosheets
      are firmly attached to PHCS according to the characterization of scanning
      electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen
      adsorption/desorption measurements. Enhanced electrochemical performance of
      MoSe2@PHCS is investigated in lithium-ion and sodium-ion storage. The MoSe2@PHCS
      deliver a reversible lithium storage capacity of 681 mA h g(-1) for 100
      discharge/charge cycles. In Na-ion batteries, it manifests a reversible sodium
      capacity of 580 mA h g(-1) after 100 cycles. Three synergic effects can be
      attributed to the enhanced electrochemical performance of MoSe2@PHCS: (1) both
      the sheet structure of the MoSe2 and the mechanically robust carbon sphere
      supporter can accommodate stress from cycling; (2) the porous hollow carbon
      spheres matrix in the MoSe2@PHCS offers a beneficial conductivity environment;
      (3) uniform and conformal MoSe2 nanosheets attachment shortens the electronic
      lithium-ion and sodium-ion pathway during cycling. The MoSe2@PHCS have a great
      potential as an anode for lithium and sodium batteries. 

PMID- 25988608
TI  - Development and Characterization of Transcription Factor Gene-Derived
      Microsatellite (TFGM) Markers in Medicago truncatula and Their Transferability in
      Leguminous and Non-Leguminous Species.
AB  - Transcription factors (TFs) are critical adaptor molecules that regulate many
      plant processes by controlling gene expression. The recent increase in the
      availability of TF data has made TFs a valuable resource for genic functional
      microsatellite marker development. In the present study, we developed TF gene
      derived microsatellite (TFGM) markers for Medicago truncatula and assessed their
      cross-species transferability. A total of 203 SSRs were identified from 1467 M.
      truncatula TF coding sequences, 87.68% of which were trinucleotide repeats,
      followed by mono- (4.93%) and hexanucleotide repeats (1.48%). Further, 142 TFGM
      markers showed a high level of transferability to the leguminous (55.63%-85.21%)
      and non-leguminous (28.17%-50.00%) species. Polymorphisms of 27 TFGM markers were
      evaluated in 44 alfalfa accessions. The allele number per marker ranged from two
      to eight with an average of 4.41, and the PIC values ranged from 0.08 to 0.84
      with an average of 0.60. Considering the high polymorphism, these TFGM markers
      developed in our study will be valuable for genetic relationship assessments,
      marker-assisted selection and comparative genomic studies in leguminous and non
      leguminous species. 

PMID- 25988609
TI  - Development and validation of a docking-based virtual screening platform for the
      identification of new lactate dehydrogenase inhibitors.
AB  - The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key
      enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells
      and is linked to the vitality of tumors in hypoxic conditions. With the aim of
      identifying new hLDH5 inhibitors, a fully automated docking-based virtual
      screening platform was developed by considering different protein conformations
      and the consensus docking strategy. In order to verify the reliability of the
      reported platform, a small database of about 10,000 compounds was filtered by
      using this method, and the top-ranked compounds were tested for their hLDH5
      inhibition activity. Enzymatic assays revealed that, among the ten selected
      compounds, two proved to efficiently inhibit enzyme activity with IC50 values in
      the micromolar range. These results demonstrate the validity of the methodologies
      we followed, encouraging the application of larger virtual screening studies and
      further refinements of the platform. Furthermore, the two active compounds herein
      described may be considered as interesting leads for the development of new and
      more efficient LDH inhibitors. 

PMID- 25988610
TI  - A structural hierarchy matching approach for molecular similarity/substructure
      searching.
AB  - An approach for molecular similarity/substructure searching based on structural
      hierarchy matching is proposed. In this approach, small molecules are divided
      into two categories, acyclic and cyclic forms. The latter are further divided
      into three structural hierarchies, namely, framework, complicated-, and mono
      rings. During searching, the similarity coefficients of a structural query and
      each retrieved molecule are calculated using the hierarchy of the query as the
      reference. A total of 13,911 chemicals were involved in this work, from which the
      minimal cyclic and acyclic substructures are extracted, and further processed
      into fuzzy structural fingerprints. Subsequently, the fingerprints are used as
      the searching indices for molecular similarity or substructure searching. The
      tests show that this approach can give user options to choose between one
      substructure and multi-substructure searching with sorted results. Moreover, this
      algorithm has the potential to be developed for molecular similarity searching
      and substructure analysis. 

PMID- 25988611
TI  - Design, synthesis and antitubercular activity of certain nicotinic Acid
      hydrazides.
AB  - Three series of 6-aryl-2-methylnicotinohydrazides 4a-i, N'-arylidene-6-(4
      bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2
      oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were
      synthesized and evaluated for their potential in vitro antimycobacterial activity
      against M. tuberculosis. The results showed that isatin hydrazides 8a-c are
      remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c
      exhibited the highest activity among all the tested compounds (MIC = 12.5 and
      6.25 ug/mL, respectively). Compounds 8b and 8c were also devoid of apparent
      cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b
      and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two
      isatin hydrazides could offer an excellent framework for future development to
      obtain more potent antitubercular agents. The SAR study suggested that
      lipophilicity of the synthesized derivatives is a crucial element that accounts
      for their antimycobacterial activity. Finally, a theoretical kinetic study was
      established to predict the ADME of the active derivatives. 

PMID- 25988612
TI  - Almond Skin Inhibits HSV-2 Replication in Peripheral Blood Mononuclear Cells by
      Modulating the Cytokine Network.
AB  - We have investigated the effect of almond skin extracts on the production of pro
      inflammatory and anti-inflammatory cytokines in human peripheral blood
      mononuclear cells (PBMCs). PBMCs were either infected or not by herpes simplex
      virus type 2 (HSV-2), with and without prior treatment with almond skin extracts.
      Production of IL-17 induced by HSV-2 was inhibited by natural skins (NS)
      treatment. NS triggered PBMC in releasing IFN-alpha, IFN-gamma and IL-4 in
      cellular supernatants. These results may explain the antiviral potential of
      almond skins. 

PMID- 25988613
TI  - Current understanding of molecular pathology and treatment of cardiomyopathy in
      duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a genetic muscle disorder caused by
      mutations in the Dmd gene resulting in the loss of the protein dystrophin.
      Patients do not only experience skeletal muscle degeneration, but also develop
      severe cardiomyopathy by their second decade, one of the main causes of death.
      The absence of dystrophin in the heart renders cardiomyocytes more sensitive to
      stretch-induced damage. Moreover, it pathologically alters intracellular calcium
      (Ca2+) concentration, neuronal nitric oxide synthase (nNOS) localization and
      mitochondrial function and leads to inflammation and necrosis, all contributing
      to the development of cardiomyopathy. Current therapies only treat symptoms and
      therefore the need for targeting the genetic defect is immense. Several
      preclinical therapies are undergoing development, including utrophin up
      regulation, stop codon read-through therapy, viral gene therapy, cell-based
      therapy and exon skipping. Some of these therapies are undergoing clinical
      trials, but these have predominantly focused on skeletal muscle correction.
      However, improving skeletal muscle function without addressing cardiac aspects of
      the disease may aggravate cardiomyopathy and therefore it is essential that
      preclinical and clinical focus include improving heart function. This review
      consolidates what is known regarding molecular pathology of the DMD heart,
      specifically focusing on intracellular Ca2+, nNOS and mitochondrial
      dysregulation. It briefly discusses the current treatment options and then
      elaborates on the preclinical therapeutic approaches currently under development
      to restore dystrophin thereby improving pathology, with a focus on the heart. 

PMID- 25988615
TI  - A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17
      hydroxylase enzyme. Synthesis and in silico molecular docking study.
AB  - A new series of 17-(N-(arylimino)-5-pregnen-3beta-ol derivatives 19-32 as well as
      carboxylate and acrylate analogues of pregnenolone 37-40 were synthesized and
      evaluated for their inhibitory activity against human CYP17 hydroxylase expressed
      in Escherichia coli. Compounds 32 and 37 were the most potent analogues in this
      series, showing inhibition activity with IC50 = 2.11 and 1.29 MUM, respectively.
      However, the analogue 37 revealed a better selectivity profile (83.21% inhibition
      of hydroxylase), which is a leading candidate for further development. Molecular
      docking study of 37 showed binding with the amino acid residues of CYP17 through
      hydrogen bonds and hydrophobic interaction.

PMID- 25988616
TI  - Diagnostic properties of ultrasound of major salivary glands in Sjogren's
      syndrome: a meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis on studies examining
      the properties of ultrasonography of major salivary glands for diagnosing
      Sjogren's syndrome. MATERIALS AND METHODS: We searched for the literature on
      eight databases. The quality of included articles was assessed with the QUADAS-2
      tool. Publication bias, pooled sensitivity, specificity, diagnostic odds ratio,
      and 95% confidence intervals (95%CI) were calculated. Meta-regression analysis
      was performed. RESULTS: We identified 37 studies and 33 ultrasonographic scoring
      systems. High risk of bias was observed in 'patient selection', 'conduct and
      interpretation of ultrasound', and 'flow of patients and timing of tests' in 78%,
      70%, and 51% of the studies. We included 29 studies in the meta-analysis.
      Publication bias was highly probable. Pooled sensitivity was 0.69 (95%CI: 0.67
      0.71), specificity 0.92 (95%CI: 0.91-0.93), and diagnostic odds ratio 33.89
      (95%CI: 20.75-55.35). Significant heterogeneity was detected between studies.
      Meta-regression analysis showed that studies with high risk of bias in 'conduct
      and interpretation of ultrasound' and studies evaluating only parenchymal
      homogeneity had higher log diagnostic odds ratio (1.09 and 2.49, respectively, p
      < 0.05). CONCLUSIONS: The quality of current studies is low, thus not allowing to
      judge the likelihood of salivary gland ultrasonography as a reliable and
      practical tool in diagnosing Sjogren's syndrome.

PMID- 25988617
TI  - In reply to the comment of Dr Asaf Achiron to a paper: Circulating anti-retinal
      antibodies in response to anti-angiogenic therapy in exudative age-related
      macular degeneration.

PMID- 25988618
TI  - Possible role of NAD-dependent glyceraldehyde-3-phosphate dehydrogenase in growth
      promotion of Arabidopsis seedlings by low levels of selenium.
AB  - We explored functional significance of selenium (Se) in Arabidopsis physiology.
      Se at very low concentrations in cultivation exerted a considerable positive
      effect on Arabidopsis growth with no indication of oxidative stress, whereas Se
      at higher concentrations significantly suppressed the growth and brought serious
      oxidative damage. Respiration, ATP levels, and the activity of NAD-dependent
      glyceraldehyde-3-phosphate dehydrogenase (NAD-GAPDH) were enhanced in Arabidopsis
      grown in the medium containing 1.0 MUM Se. Addition of an inhibitor of
      glutathione (GSH) synthesis to the medium abolished both of the Se-dependent
      growth promotion and NAD-GAPDH up-regulation. Assay of NAD-GAPDH purified from
      seedlings subjected to Se interventions raised the possibility of a direct
      connection between the activity of this enzyme and Arabidopsis growth. These
      results reveal that trace amounts of Se accelerate Arabidopsis growth, and
      suggest that this pro-growth effect of Se arises enhancing mitochondrial
      performance in a GSH-dependent manner, in which NAD-GAPDH may serve as a key
      regulator.

PMID- 25988620
TI  - The countertransference impact of autistic defence in an otherwise neurotic
      patient.
AB  - This paper investigates the question of why, in the psychoanalytic psychotherapy
      of a patient with encapsulated autistic pathology, the steady maintenance of a
      therapeutically neutral stance can be especially difficult. Transference and
      countertransference vicissitudes are examined. The author notices that the
      patient's intolerance of 'opposites' (cf. Tustin, 1986), combined with extreme
      antipathy to having that intolerance noticed, can elicit corresponding, and
      potentially destabilizing, countertransference reactions. These reactions
      comprise an unstable tension between co-existing pressures towards fusion with,
      or expulsion of, the patient, their co-existence under further pressure to remain
      unnoticed. Until perceived, this state of affairs risks collusion with the
      pressure either to merge with or to expel the patient, and compromises the
      capacity to notice the detail of the transference process and even to notice co
      existent positive and negative transference images. Detailed clinical
      illustration is given, including a session where it was difficult to notice the
      patient's experience of a couple as a combined object. The author finds these
      observations of bipolar countertransference tensions illuminated by Green's
      concepts of positive and negative narcissism and of the disobjectalizing
      function, and specifically accounted for by Ribas's theory of autism as radical
      drive defusion. 

PMID- 25988619
TI  - Identification of distinct layers within the stratified squamous epithelium of
      the adult human true vocal fold.
AB  - OBJECTIVES/HYPOTHESIS: A precise molecular schema for classifying the different
      cell types of the normal human vocal fold epithelium is lacking. We hypothesize
      that the true vocal fold epithelium has a cellular architecture and organization
      similar to that of other stratified squamous epithelia including the skin,
      cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and
      gastrointestinal tract, a molecular definition of the normal cell types within
      the human vocal fold epithelium and a description of their geometric
      relationships should serve as a foundation for characterizing cellular changes
      associated with metaplasia, dysplasia, and cancer. STUDY DESIGN: Qualitative
      study with adult human larynges. METHODS: Histologic sections of normal human
      laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and
      immunohistochemical protein expression profile, including cytokeratins (CK13 and
      CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and
      proliferation markers (Ki67). RESULTS: We demonstrated that three distinct cell
      strata with unique marker profiles are present within the stratified squamous
      epithelium of the true vocal fold. We used these definitions to establish that
      cell proliferation is restricted to certain cell types and layers within the
      epithelium. These distinct cell types are reproducible across five normal adult
      larynges. CONCLUSION: We have established that three layers of cells are present
      within the normal adult stratified squamous epithelium of the true vocal fold.
      Furthermore, replicating cell populations are largely restricted to the parabasal
      strata within the epithelium. This delineation of distinct cell populations will
      facilitate future studies of vocal fold regeneration and cancer. LEVEL OF
      EVIDENCE: N/A.

PMID- 25988614
TI  - On the role of skin in the regulation of local and systemic steroidogenic
      activities.
AB  - The mammalian skin is a heterogeneous organ/tissue covering our body, showing
      regional variations and endowed with neuroendocrine activities. The latter is
      represented by its ability to produce and respond to neurotransmitters,
      neuropeptides, hormones and neurohormones, of which expression and phenotypic
      activities can be modified by ultraviolet radiation, chemical and physical
      factors, as well as by cytokines. The neuroendocrine contribution to the
      responses of skin to stress is served, in part, by local synthesis of all
      elements of the hypothalamo-pituitary-adrenal axis. Skin with subcutis can also
      be classified as a steroidogenic tissue because it expresses the enzyme, CYP11A1,
      which initiates steroid synthesis by converting cholesterol to pregnenolone, as
      in other steroidogenic tissues. Pregnenolone, or steroidal precursors from the
      circulation, are further transformed in the skin to corticosteroids or sex
      hormones. Furthermore, in the skin CYP11A1 acts on 7-dehydrocholesterol with
      production of 7-dehydropregnolone, which can be further metabolized to other
      Delta7steroids, which after exposure to UVB undergo photochemical transformation
      to vitamin D like compounds with a short side chain. Vitamin D and lumisterol,
      produced in the skin after exposure to UVB, are also metabolized by CYP11A1 to
      several hydroxyderivatives. Vitamin D hydroxyderivatives generated by action of
      CYP11A1 are biologically active and are subject to further hydroxylations by
      CYP27B1, CYP27A1 and CP24A. Establishment of which intermediates are produced in
      the epidermis in vivo and whether they circulate on the systemic level represent
      a future research challenge. In summary, skin is a neuroendocrine organ endowed
      with steroid/secosteroidogenic activities. 

PMID- 25988621
TI  - Lumiquinone A, an alpha-Aminomalonate-Derived Aminobenzoquinone from Photorhabdus
      luminescens.
AB  - Lumiquinone A (1), an unusual aminobenzoquinone member within the phenylpropanoid
      class of natural products, together with the known compound 3,5-dihydroxy-4
      isopropyl-trans-stilbene (2), was isolated from the entomopathogenic bacterium
      Photorhabdus luminescens TT01. On the basis of the analysis of extensive 2D NMR
      and high-resolution ESI-QTOF-MS spectral data, the structure of 1 was determined
      to be a 2-amino-5-hydroxy-1,4-benzoquinone substituted with (E)-2-phenylvinyl and
      isopropyl functional groups. Free alpha-aminomalonate medium supplementation
      significantly enhanced production of 1 relative to 2 in a dose-dependent manner,
      suggesting that promiscuous polyketide synthase processing of malonate- versus
      alpha-aminomalonate-derived substrates represents a competitive route for
      polyketide structural diversification. Metabolites 1 and 2 were active against
      Bacillus subtilis and Saccharomyces cerevisiae. 

PMID- 25988623
TI  - Excess in moderation: general anesthesia for cesarean delivery.

PMID- 25988624
TI  - Infusion systems: the infrastructure of modern anesthesia.

PMID- 25988625
TI  - A spotlight on obstetric anesthesia in the developing world: finally getting the
      attention it deserves.

PMID- 25988626
TI  - Sleep, pain, and breathing.

PMID- 25988622
TI  - The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation
      Lymphoproliferative Disorder.
AB  - We examined the associations of Epstein-Barr virus (EBV) status with
      characteristics and outcomes of posttransplantation lymphoproliferative disorder
      (PTLD) by studying 176 adult solid organ transplant recipients diagnosed with
      PTLD between 1990 and 2013 (58 [33%] EBV-negative; 118 [67%] EBV-positive). The
      proportion of EBV-negative cases increased over time from 10% (1990-1995) to 48%
      (2008-2013) (p < 0.001). EBV-negative PTLD had distinct characteristics
      (monomorphic histology, longer latency) though high-risk features (advanced
      stage, older age, high lactate dehydrogenase, central nervous system involvement)
      were not more common compared to EBV-positive PTLD. In multivariable analysis,
      EBV negativity was not significantly associated with worse response to initial
      therapy (adjusted odds ratio, 0.84; p = 0.75). The likelihood of achieving a
      complete remission (CR) was not significantly different for EBV-negative versus
      EBV-positive PTLD including when therapy was reduction of immunosuppression alone
      (35% vs. 43%, respectively, p = 0.60) or rituximab (43% vs. 47%, p = 1.0). EBV
      negativity was also not associated with worse overall survival (adjusted hazard
      ratio, 0.91; p = 0.71). Our findings indicate that EBV status is not prognostic
      or predictive of treatment response in adults with PTLD. The high proportion of
      EBV-negative disease diagnosed in recent years highlights the need for new
      strategies for prevention and management of EBV-negative PTLD.

PMID- 25988627
TI  - Portable infrared pupillometry: ready for prime time?

PMID- 25988628
TI  - Monitoring for carotid endarterectomy: more or less?

PMID- 25988629
TI  - Waiting to exhale: neuraxial anesthesia in patients with chronic obstructive
      pulmonary disease.

PMID- 25988630
TI  - The evolution of perioperative transfusion testing and blood ordering.
AB  - The evolution of modern anesthesia and surgical practices has been accompanied by
      enhanced supportive procedures in blood banking and transfusion medicine. There
      is increased focus on the preparation and the use of blood components including,
      but not limited to, preventing unnecessary type and screen/crossmatch orders,
      decreasing the time required to provide compatible red blood cells (RBCs), and
      reducing the waste of limited blood and personnel resources. The aim of this
      review is to help the anesthesiologist and surgical staff identify patients at
      highest risk for surgical bleeding. In addition, this review examines how
      anesthesia and transfusion medicine can efficiently and safely allocate blood
      components for surgical patients who require transfusions. The following
      databases were searched: PubMed, EMBASE, Google Scholar, and the Cochrane Library
      from January 1970 through March 2014. Subsequent reference searches of retrieved
      articles were also assessed. Several innovations have drastically changed the
      procedures by which blood is ordered, inventoried, and the speed in which blood
      is delivered for patient care. Before entering an operating room, patient blood
      management provides guidance to clinicians about when and how to treat
      preoperative anemia and intra- and postoperative strategies to limit the
      patient's exposure to blood components. Timely updates of the recommendations for
      blood orders (maximum surgical blood ordering schedule) have enhanced
      preoperative decision making regarding the appropriateness of the type and screen
      versus the type and crossmatch order. The updated maximum surgical blood ordering
      schedule reflects modern practices, such as laparoscopy, improved surgical
      techniques, and use of hemostatic agents resulting in a more streamlined process
      for ordering and obtaining RBCs. The electronic (computer) crossmatch and
      electronic remote blood issue have also dramatically reduced the amount of time
      required to obtain crossmatch-compatible RBCs when compared with the more
      traditional serologic crossmatch methods. These changes in blood banking methods
      have resulted in more efficient delivery of blood to surgical patients. 

PMID- 25988632
TI  - Echocardiographic Artifact Induced by HeartWare Left Ventricular Assist Device.

PMID- 25988631
TI  - Real-Time Transesophageal Echocardiography for Left Atrial Appendage Ligation
      Using the LARIAT Snare Device.

PMID- 25988633
TI  - Postoperative sleep-disordered breathing in patients without preoperative sleep
      apnea.
AB  - BACKGROUND: Recently published data show that postoperative apnea-hypopnea index
      (AHI) is significantly increased in some patients without preoperative sleep
      apnea. These patients may be at risk of developing perioperative adverse events
      related to sleep-disordered breathing (SDB). The objective of this study was to
      investigate the incidence and predictors of postoperative moderate-to-severe SDB
      (AHI > 15 events/h) in patients without sleep apnea preoperatively. METHODS: In a
      prospective observational fashion, patients were invited to undergo sleep studies
      with a portable device (Embletta X100) preoperatively at home and postoperatively
      on the first and third night after surgery in the hospital or at home. The
      primary outcome was the incidence of postoperative moderate-to-severe SDB (AHI >
      15 events/h) in non-sleep apnea patients (preoperative AHI <= 5 events/h).
      Logistic regression was used to evaluate the association of clinical factors and
      preoperative sleep parameters with the occurrence of postoperative moderate-to
      severe SDB. RESULTS: A total of 120 non-sleep apnea patients completed the study,
      of which 31 (25.8% [95% confidence interval: 18.3%-34.6%]) patients were found to
      have AHI > 15 events/h on postoperative night 1 and/or postoperative night 3
      (postoperative SDB group), and 89 (74%) patients had an AHI <= 15 events/h on
      both postoperative night 1 and 3 (postoperative non-SDB group). The patients in
      the postoperative SDB group were older (60 +/- 13 vs 53 +/- 12 years, P = 0.008)
      with more smokers (32.3% vs 15.7%, P = 0.048) and had a greater increase in the
      obstructive apnea index (adjusted P = 0.0003), central apnea index (adjusted P =
      0.0012), and hypopnea index (adjusted P = 0.0004). Multivariate logistic
      regression analysis found that age and preoperative respiratory disturbance index
      (RDI) were significantly associated with the occurrence of postoperative moderate
      to-severe SDB, P = 0.018 and P = 0.006, respectively. The sensitivity privilege
      cutoff of RDI at 4.9 events/h identified 70.2% to 96.4%patients developing
      postoperative moderate-to-severe SDB. CONCLUSIONS: At least 18.3% of non-sleep
      apnea patients developed moderate-to-severe SDB after surgery. Age and
      preoperative RDI were associated with the occurrence of postoperative moderate-to
      severe SDB.

PMID- 25988634
TI  - Portable infrared pupillometry: a review.
AB  - Portable infrared pupillometers provide an objective measure of pupil size and
      pupillary reflexes, which for most clinicians was previously only a visual
      impression. But despite the fact that pupillometry can uncover aspects of how the
      human pupil reacts to drugs and noxious stimulation, the use of pupillometry has
      not gained widespread use among anesthesiologists and critical care physicians.
      The present review is an introduction to the physiology of pupillary reflexes and
      the currently established clinical applications of infrared pupillometry, which
      will hopefully encourage physicians to use this diagnostic tool in their clinical
      practice. Portable infrared pupillometry was introduced in 1989. The technology
      involves flooding the eye with infrared light and then measuring the reflected
      image on an infrared sensor. Pupil size, along with variables of the pupillary
      light reflex and pupillary reflex dilation, is calculated by the instrument and
      displayed on a screen immediately after each time-stamped measurement. Use of
      these instruments has uncovered aspects of how the human pupil reacts to drugs
      and noxious stimulation. The primary clinical applications for portable
      pupillometry have been in the assessment of brainstem function. Portable
      pupillometry is useful in the management of pain because it allows for
      assessments of the effect of opioids and in the titration of combined regional
      general anesthetics. 

PMID- 25988635
TI  - The environmental impact of the Glostavent(r) anesthetic machine.
AB  - Because anesthetic machines have become more complex and more expensive, they
      have become less suitable for use in the many isolated hospitals in the poorest
      countries in the world. In these situations, they are frequently unable to
      function at all because of interruptions in the supply of oxygen or electricity
      and the absence of skilled technicians for maintenance and servicing. Despite
      these disadvantages, these machines are still delivered in large numbers, thereby
      expending precious resources without any benefit to patients. The Glostavent was
      introduced primarily to enable an anesthetic service to be delivered in these
      difficult circumstances. It is smaller and less complex than standard anesthetic
      machines and much less expensive to produce. It combines a drawover anesthetic
      system with an oxygen concentrator and a gas-driven ventilator. It greatly
      reduces the need for the purchase and transport of cylinders of compressed gases,
      reduces the impact on the environment, and enables considerable savings. Cylinder
      oxygen is expensive to produce and difficult to transport over long distances on
      poor roads. Consequently, the supply may run out. However, when using the
      Glostavent, oxygen is normally produced at a fraction of the cost of cylinders by
      the oxygen concentrator, which is an integral part of the Glostavent. This
      enables great savings in the purchase and transport cost of oxygen cylinders. If
      the electricity fails and the oxygen concentrator ceases to function, oxygen from
      a reserve cylinder automatically provides the pressure to drive the ventilator
      and oxygen for the breathing circuit. Consequently, economy is achieved because
      the ventilator has been designed to minimize the amount of driving gas required
      to one-seventh of the patient's tidal volume. Additional economies are achieved
      by completely eliminating spillage of oxygen from the breathing system and by
      recycling the driving gas into the breathing system to increase the Fraction of
      Inspired Oxygen (FIO2) at no extra cost. Savings also are accrued when using the
      drawover breathing system as the need for nitrous oxide, compressed air, and soda
      lime are eliminated. The Glostavent enables the administration of safe anesthesia
      to be continued when standard machines are unable to function and can do so with
      minimal harm to the environment. 

PMID- 25988636
TI  - Chronic opioid use and central sleep apnea: a review of the prevalence,
      mechanisms, and perioperative considerations.
AB  - BACKGROUND: Chronic opioid use has been associated with the development of sleep
      disordered breathing (SDB) such as central sleep apnea (CSA). Patients receiving
      chronic opioids may suffer from unrecognized sleep apnea that contributes to
      opioid-overdose death. Currently, information regarding the perioperative
      management of patients with chronic opioid-associated CSA is limited. The
      objectives of this review are to define the clinical manifestations of SDB
      associated with chronic opioid therapy, especially CSA, and to highlight their
      prevalence, mechanisms, risk factors, and perioperative management. METHODS: We
      searched Medline (1983-2014), Medline In-Process and other nonindexed citations
      (July 2014), EMBASE (1983-2014), the Cochrane Database of Systematic Reviews
      (January 2005-2014), the Cochrane Central Registry of Controlled Trials (July
      2014), and PubMed basic search for new materials (1983-2014). Anesthesia and
      Sleep Medicine meeting abstracts were also searched for relevant articles. We
      included all prospective, retrospective studies and case reports in which CSA and
      chronic opioid use was confirmed by polysomnography. CSA was defined as the
      absence of airflow for >= 10 seconds with the absence of breathing efforts. A
      Central Apnea Index >= 5 events/h was considered significant. RESULTS: The search
      strategy yielded 8 studies which included 560 patients. The overall prevalence of
      CSA in patients taking chronic opioids was high (24%). The morphine equivalent
      daily dose (MEDD) was strongly associated with the severity of the SDB,
      predominantly CSA, with an MEDD of >200 mg being a threshold of particular
      concern. Concurrent use of benzodiazepines or hypnotics was associated with the
      severity of CSA in one study. Body mass index was inversely related to the
      severity of SDB. There were various recommendations regarding the best type of
      positive airway pressure therapy for the treatment of opioid-associated CSA.
      Continuous positive airway pressure may be ineffective in eliminating, or may
      even increase, CSA. Adaptive servoventilation and bilevel positive airway
      pressure ventilation were effective according to some reports. CONCLUSIONS: The
      overall prevalence of CSA in patients taking chronic opioids was 24%. The most
      important risk factors for severity of CSA were an MEDD >200 mg, and low or
      normal body mass index. Continuous positive airway pressure is often ineffective
      for treating CSA. Limited data are available on the perioperative management of
      patients with CSA associated with chronic opioid use. Further prospective studies
      on the perioperative risks and management of these patients are needed.

PMID- 25988637
TI  - Teaching neuraxial anesthesia techniques for obstetric care in a Ghanaian
      referral hospital: achievements and obstacles.
AB  - Anesthesia providers in low-income countries may infrequently provide regional
      anesthesia techniques for obstetrics due to insufficient training and supplies,
      limited manpower, and a lack of perceived need. In 2007, Kybele, Inc. began a 5
      year collaboration in Ghana to improve obstetric anesthesia services. A program
      was designed to teach spinal anesthesia for cesarean delivery and spinal labor
      analgesia at Ridge Regional Hospital, Accra, the second largest obstetric unit in
      Ghana. The use of spinal anesthesia for cesarean delivery increased significantly
      from 6% in 2006 to 89% in 2009. By 2012, >90% of cesarean deliveries were
      conducted with spinal anesthesia, despite a doubling of the number performed. A
      trial of spinal labor analgesia was assessed in a small cohort of parturients
      with minimal complications; however, protocol deviations were observed. Although
      subsequent efforts to provide spinal analgesia in the labor ward were hampered by
      anesthesia provider shortages, spinal anesthesia for cesarean delivery proved to
      be practical and sustainable. 

PMID- 25988639
TI  - A comparison of plaintiff and defense expert witness qualifications in
      malpractice litigation in anesthesiology.
AB  - BACKGROUND: Expert witnesses serve a crucial role in the medicolegal system,
      interpreting evidence so that it can be understood by jurors. Guidelines have
      been established by both the legal community and professional medical societies
      detailing the expectations of expert witnesses. The primary objective of this
      analysis was to evaluate the expertise of anesthesiologists testifying as expert
      witnesses in malpractice litigation. METHODS: The WestlawNext legal database was
      searched for cases over the last 5 years in which anesthesiologists served as
      expert witnesses. Internet searches were used to identify how long each witness
      had been in practice. Departmental websites, the Scopus database, and state
      medical licensing boards were used to measure scholarly impact (via the h-index)
      and determine whether the witness was a full-time faculty member in academia.
      RESULTS: Anesthesiologists testifying in 295 cases since 2008 averaged over 30
      years of experience per person (mean +/- SEM, defense, 33.4 +/- 0.7, plaintiff,
      33.1 +/- 0.6, P = 0.76). Individual scholarly impact, as measured by h-index, was
      found to be lower among plaintiff experts (mean +/- SEM, 4.8 +/- 0.5) than their
      defendant counterparts (mean +/- SEM, 8.1 +/- 0.8; P = 0.02). A greater
      proportion of defense witnesses were involved in academic practice (65.7% vs
      54.8%, P = 0.04). CONCLUSIONS: Anesthesiologists testifying for both sides are
      very experienced. Defense expert witnesses are more likely to have a higher
      scholarly impact and to practice in an academic setting. This indicates that
      defense expert witnesses may have greater expertise than plaintiff expert
      witnesses.

PMID- 25988640
TI  - To stop or not?

PMID- 25988638
TI  - Outcomes for extremely premature infants.
AB  - Premature birth is a significant cause of infant and child morbidity and
      mortality. In the United States, the premature birth rate, which had steadily
      increased during the 1990s and early 2000s, has decreased annually for 7 years
      and is now approximately 11.39%. Human viability, defined as gestational age at
      which the chance of survival is 50%, is currently approximately 23 to 24 weeks in
      developed countries. Infant girls, on average, have better outcomes than infant
      boys. A relatively uncomplicated course in the intensive care nursery for an
      extremely premature infant results in a discharge date close to the prenatal
      estimated date of confinement. Despite technological advances and efforts of
      child health experts during the last generation, the extremely premature infant
      (less than 28 weeks gestation) and extremely low birth weight infant (<1000 g)
      remain at high risk for death and disability with 30% to 50% mortality and, in
      survivors, at least 20% to 50% risk of morbidity. The introduction of continuous
      positive airway pressure, mechanical ventilation, and exogenous surfactant
      increased survival and spurred the development of neonatal intensive care in the
      1970s through the early 1990s. Routine administration of antenatal steroids
      during premature labor improved neonatal mortality and morbidity in the late
      1990s. The recognition that chronic postnatal administration of steroids to
      infants should be avoided may have improved outcomes in the early 2000s. Evidence
      from recent trials attempting to define the appropriate target for oxygen
      saturation in preterm infants suggests arterial oxygen saturation between 91% and
      95% (compared with 85%-89%) avoids excess mortality; however, final analyses of
      data from these trials have not been published, so definitive recommendations are
      still pending. The development of neonatal neurocritical intensive care units may
      improve neurocognitive outcomes in this high-risk group. Long-term follow-up to
      detect and address developmental, learning, behavioral, and social problems is
      critical for children born at these early gestational ages.The striking
      similarities in response to extreme prematurity in the lung and brain imply that
      agents and techniques that benefit one organ are likely to also benefit the
      other. Finally, because therapy and supportive care continue to change, the
      outcomes of extremely low birth weight infants are ever evolving. Efforts to
      minimize injury, preserve growth, and identify interventions focused on
      antioxidant and anti-inflammatory pathways are now being evaluated. Thus,
      treating and preventing long-term deficits must be developed in the context of a
      "moving target." 

PMID- 25988642
TI  - Blocks of the anterior abdominal wall: local and systemic effect?

PMID- 25988641
TI  - Residency board certification requirements and preoperative surgical home
      activities in the United States: comparing anesthesiology, family medicine,
      internal medicine, and surgery.

PMID- 25988643
TI  - Longer times to reanesthetization with longer anesthetic duration?

PMID- 25988644
TI  - Questions on prevention of newborn hypothermia after cesarean delivery.

PMID- 25988645
TI  - In response.

PMID- 25988646
TI  - Core temperature monitoring.

PMID- 25988647
TI  - Early physician anesthetists in the United States.

PMID- 25988649
TI  - A novel interstitial deletion of 2q22.3 q23.3 in a patient with dysmorphic
      features, epilepsy, aganglionosis, pure red cell aplasia, and skeletal
      malformations.
AB  - Many chromosomal deletions encompassing the 2q23.1 region have been described
      ranging from small deletions of 38 kb up to >19 Mb. Most phenotypic features of
      the 2q23.1 deletion syndrome are due to a MBD5 gene loss independent of the size
      of the deletion. Here, we describe a male patient harboring a novel interstitial
      deletion encompassing the 2q22.3 q23.3 chromosomal region. Array-CGH revealed a
      7.1 Mb deletion causing haploinsufficiency of several genes including MBD5,
      ACVR2, KIF5C, and EPC2. This patient presents with additional findings to those
      already described in individuals who have deletions of MBD5 including toes
      absence of halluces, pure red cell aplasia, and intestinal aganglionosis.
      Interestingly, in the deleted region there are previously identified regulatory
      sequences which are located upstream to ZEB2, which is associated with
      Hirschsprung disease (HSCR). Several genes have been associated with pure red
      cell aplasia, but to our knowledge, this is the first time that 2q deletion is
      associated with this phenotype. These additional findings should be added to the
      list of manifestations associated with 2q deletion, and provide support for the
      hypothesis that this individual has a true contiguous gene deletion syndrome.

PMID- 25988650
TI  - [Final reply, quality registries: Time to discuss the core of science and quality
      criteria].

PMID- 25988651
TI  - [The Medical Products Agency is positive to a dialogue about off-label
      prescribing].

PMID- 25988652
TI  - [The medical society of anthroposophic medicine: Allow anthroposophic medicines
      in Sweden].

PMID- 25988653
TI  - [Not Available].

PMID- 25988654
TI  - Role of crystallins in diabetic complications.
AB  - BACKGROUND: Crystallins are the major structural proteins of vertebrate eye lens
      responsible for maintaining the refractive index of the lens. However, recent
      studies suggest that they also have a functional significance in non-lenticular
      tissues. Prolonged uncontrolled diabetes results in the development of macro and
      microvascular complications that are the leading causes of morbidity and
      mortality in diabetic patients all over the world. SCOPE OF REVIEW: Recent
      studies have shown that crystallins play an instrumental role in diabetes and its
      complications. Therefore, this review highlights the current data on the impact
      of chronic hyperglycemia on expression, distribution, glycation, phosphorylation,
      chaperone-like function and, anti-apoptotic activity of crystallins. Furthermore,
      we discussed the insights for developing therapeutic strategies for diabetic
      complications including natural agents, peptides, and pharmacological chaperones
      that modulate or mimic chaperone activity of alpha-crystallins. MAJOR
      CONCLUSIONS: Upregulation of crystallins appears to be a common feature of
      chronic diabetes. Further, chronic hyperglycemia induces the glycation and
      phosphorylation of crystallins, mainly alpha-crystallins and thereby alters their
      properties. The disturbed interaction of alphaB-crystallin with various apoptotic
      mediators including Bax and caspases is also an important factor for increased
      cell death in diabetes. Numerous dietary agents, peptides, and chemical
      chaperones prevent apoptosis and the loss of chaperone activity in diabetes.
      GENERAL SIGNIFICANCE: Understanding the role of crystallins will aid in
      developing therapeutic strategies for alleviating pathophysiological conditions
      such as protein aggregation, inflammation, oxidative stress and apoptosis
      associated with chronic complications of diabetes including cataract,
      retinopathy, and cardiomyopathy. This article is part of a Special Issue entitled
      Crystallin Biochemistry in Health and Disease.

PMID- 25988657
TI  - Effect of divalent Ba cation substitution with Sr on coupled 'multiglass' state
      in the magnetoelectric multiferroic compound Ba3NbFe3Si2O14.
AB  - (Ba/Sr)3NbFe3Si2O14 is a magneto-electric multiferroic with an incommensurate
      antiferromagnetic spiral magnetic structure which induces electric polarization
      at 26 K. Structural studies show that both the compounds have similar crystal
      structure down to 6 K. They exhibit a transition, TN at 26 K and 25 K
      respectively, as indicated by heat capacity and magnetization, into an
      antiferromagnetic state. Although Ba and Sr are isovalent, they exhibit very
      different static and dynamic magnetic behaviors. The Ba-compound exhibits a
      glassy behavior with critical slowing dynamics with a freezing temperature of ~35
      K and a critical exponent of 3.9, a value close to the 3-D Ising model above TN,
      in addition to the invariant transition into an antiferromagnetic state. The Sr
      compound however does not exhibit any dispersive behavior except for the
      invariant transition at TN. The dielectric constant reflects magnetic behavior of
      the two compounds: the Ba-compound has two distinct dispersive peaks while the Sr
      compound has a single dispersive peak. Thus the compounds exhibit coupled
      'multiglass' behavior. The difference in magnetic properties between the two
      compounds is found to be due to modifications to super exchange path angle and
      length as well as anti-site defects which stabilize either ferromagnetic or
      antiferromagnetic interactions.

PMID- 25988658
TI  - Stable Iridium(IV) Complexes of an Oxidation-Resistant Pyridine-Alkoxide Ligand:
      Highly Divergent Redox Properties Depending on the Isomeric Form Adopted.
AB  - The preparation of the facial and meridional isomers of [Ir(pyalk)3] (pyalk = 2
      (2-pyridyl)isopropanoate), as model complexes for a powerful water oxidation
      catalyst, is reported. The strongly donating N3O3 ligand set is very oxidation
      resistant, yet promotes facile metal-centered oxidation to form stable Ir(IV)
      compounds. The Ir(III/IV) reduction potentials of the two isomers differ by 340
      mV despite the identical ligand set. A ligand field rationalization is advanced
      and supported by DFT calculations. 

PMID- 25988659
TI  - The role of the sphingosine-1-phosphate signaling pathway in osteocyte
      mechanotransduction.
AB  - Osteocytes are proposed to be the mechanosensory cells that translate mechanical
      loading into biochemical signals during the process of bone adaptation. The lipid
      mediator sphingosine-1-phosphate (S1P) has been reported to play a role in the
      mechanotransduction process of blood vessels and also in the dynamic control of
      bone mineral homeostasis. Nevertheless, the potential role of S1P in bone
      mechanotransduction has yet to be elucidated. In this study, we hypothesized that
      a S1P cascade is involved in the activation of osteocytes in response to loading
      induced oscillatory fluid flow (OFF) in bone. MLO-Y4 osteocyte-like cells express
      the necessary components of a functional S1P cascade. To examine the involvement
      of S1P signaling in osteocyte mechanotransduction, we applied OFF (1 Pa, 1 Hz) to
      osteocyte-like MLO-Y4 cells under conditions where the S1P signaling pathway was
      modulated. We found that decreased endogenous S1P levels significantly suppressed
      the OFF-induced intracellular calcium response. Addition of extracellular S1P to
      MLO-Y4 cells enhanced the synthesis and release of prostaglandin E2 (PGE2) under
      static cells and amplified OFF-induced PGE2 release. The stimulatory effect of
      OFF on the gene expression levels of osteoprotegerin (OPG) and receptor activator
      for nuclear factor kappaB ligand (RANKL) was S1P dependent. Furthermore, the S1P2
      receptor subtype was shown to be involved in OFF-induced PGE2 synthesis and
      release, as well as down-regulation of RANKL/OPG gene expression ratio. In
      summary, our data suggest that S1P cascade is involved in OFF-induced
      mechanotransduction in MLO-Y4 cells and that extracellular S1P exerts its effect
      partly through S1P2 receptors.

PMID- 25988661
TI  - Donor Nucleotide-Binding Oligomerization-Containing Protein 2 (NOD2) Single
      Nucleotide Polymorphism 13 Is Associated with Septic Shock after Allogeneic Stem
      Cell Transplantation.
AB  - Single nucleotide polymorphisms (SNPs) within nucleotide-binding oligomerization
      domain-containing protein 2 (NOD2) and toll-like receptor (TLR) 5 genes have been
      recently associated with the incidence and outcome of infections. In this study,
      we analyzed 38 patients with septic shock after allogeneic stem cell
      transplantation (allo-SCT) for an association of SNPs within NOD2 and TLR5 genes,
      with susceptibility to septic shock. One hundred twenty-seven transplant
      recipients unaffected by any infectious complications were used as controls. We
      found a significant association between the presence of donor NOD2 SNP13
      (3016_3017insC) and the incidence of septic shock (P = .002). In multivariate
      analysis, donor NOD2 SNP13 appeared as an independent risk factor for the
      incidence of septic shock after allo-SCT. No association was found for recipient
      SNPs (NOD2 and TLR5) and donor NOD2 SNP8, SNP12, and TLR5-Stop SNP. Our results
      suggest that NOD2 SNP13 has an impact on the pathophysiology of severe infectious
      complications and is an independent risk factor for the development of septic
      shock after allo-SCT.

PMID- 25988662
TI  - Comments on "diagnosis and management of osteonecrosis of the jaw: a systematic
      review and international consensus".

PMID- 25988660
TI  - Trabecular bone score (TBS) as a new complementary approach for osteoporosis
      evaluation in clinical practice.
AB  - Trabecular bone score (TBS) is a recently-developed analytical tool that performs
      novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry
      (DXA) images, and thereby captures information relating to trabecular
      microarchitecture. In order for TBS to usefully add to bone mineral density (BMD)
      and clinical risk factors in osteoporosis risk stratification, it must be
      independently associated with fracture risk, readily obtainable, and ideally,
      present a risk which is amenable to osteoporosis treatment. This paper summarizes
      a review of the scientific literature performed by a Working Group of the
      European Society for Clinical and Economic Aspects of Osteoporosis and
      Osteoarthritis. Low TBS is consistently associated with an increase in both
      prevalent and incident fractures that is partly independent of both clinical risk
      factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More
      recently, TBS has been shown to have predictive value for fracture independent of
      fracture probabilities using the FRAX(r) algorithm. Although TBS changes with
      osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and
      it is not clear how change in TBS relates to fracture risk reduction. TBS may
      also have a role in the assessment of fracture risk in some causes of secondary
      osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced
      osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment
      in combination with both aBMD and FRAX. 

PMID- 25988665
TI  - Acetonitrile as a cyanating reagent: Cu-catalyzed cyanation of arenes.
AB  - A novel approach to the Cu-catalyzed cyanation of simple arenes using
      acetonitrile as an attractive cyano source has been documented. The C-H
      functionalization of arenes without directing groups involves a sequential
      iodination/cyanation to give the desired aromatic nitriles in good yields. A
      highly efficient Cu/TEMPO system for acetonitrile C-CN bond cleavage has been
      discovered. TEMPO is used as a cheap oxidant and enables the reaction to be
      catalytic in copper. Moreover, TEMPOCH2CN 6 has been identified as the active
      cyanating agent and shows high reactivity for forming the -CN moiety. 

PMID- 25988664
TI  - Human cell adhesion molecules: annotated functional subtypes and
      overrepresentation of addiction-associated genes.
AB  - Human cell adhesion molecules (CAMs) are essential for proper development,
      modulation, and maintenance of interactions between cells and cell-to-cell (and
      matrix-to-cell) communication about these interactions. Despite the differential
      functional significance of these roles, there have been surprisingly few
      systematic studies to enumerate the universe of CAMs and identify specific CAMs
      in distinct functions. In this paper, we update and review the set of human genes
      likely to encode CAMs with searches of databases, literature reviews, and
      annotations. We describe likely CAMs and functional subclasses, including CAMs
      that have a primary function in information exchange (iCAMs), CAMs involved in
      focal adhesions, CAM gene products that are preferentially involved with
      stereotyped and morphologically identifiable connections between cells (e.g.,
      adherens junctions, gap junctions), and smaller numbers of CAM genes in other
      classes. We discuss a novel proposed mechanism involving selective anchoring of
      the constituents of iCAM-containing lipid rafts in zones of close neuronal
      apposition to membranes expressing iCAM binding partners. We also discuss data
      from genetic and genomic studies of addiction in humans and mouse models to
      highlight the ways in which CAM variation may contribute to a specific brain
      based disorder such as addiction. Specific examples include changes in CAM mRNA
      splicing mediated by differences in the addiction-associated splicing regulator
      RBFOX1/A2BP1 and CAM expression in dopamine neurons. 

PMID- 25988666
TI  - Silver nanoparticle aggregates on metal fibers for solid phase microextraction
      surface enhanced Raman spectroscopy detection of polycyclic aromatic
      hydrocarbons.
AB  - Solid phase microextraction (SPME), a solvent free technique for sample
      preparation, has been successfully coupled with GC, GC-MS, and HPLC for
      environmental analysis. In this work, a method combining solid phase
      microextraction with surface enhanced Raman spectroscopy (SERS) is developed for
      detection of polycyclic aromatic hydrocarbons (PAHs). Silver nanoparticle
      aggregates were deposited on the Ag-Cu fibers via layer-by-layer deposition,
      which were modified with propanethiol (PTH). The SERS-active SPME fiber was
      immersed in water directly to extract PAHs and then detected using a portable
      Raman spectrometer. The pronounced valence vibration of the C-C bond at 1030 cm(
      1) was chosen as an internal standard peak for the constant concentration of PTH.
      The RSD values of the stability and the uniformity of the SERS-active SPME fiber
      are 2.97% and 5.66%, respectively. A log-log plot of the normalized SERS
      intensity versus fluoranthene concentration showed a linear relationship (R(2) =
      0.95). The detection limit was 7.56 * 10(-10) M and the recovery rate of water
      samples was in the range of 95% to 115%. The method can also be applied to
      detection of PAH mixtures, and each component of the mixtures can be
      distinguished by Raman characteristic peaks. The SERS-active SPME fiber could be
      further confirmed by GC-MS. 

PMID- 25988667
TI  - Multistability in a class of stochastic delayed Hopfield neural networks.
AB  - In this paper, multistability analysis for a class of stochastic delayed Hopfield
      neural networks is investigated. By considering the geometrical configuration of
      activation functions, the state space is divided into 2(n) + 1 regions in which
      2(n) regions are unbounded rectangles. By applying Schauder's fixed-point theorem
      and some novel stochastic analysis techniques, it is shown that under some
      conditions, the 2(n) rectangular regions are positively invariant with
      probability one, and each of them possesses a unique equilibrium. Then by
      applying Lyapunov function and functional approach, two multistability criteria
      are established for ensuring these equilibria to be locally exponentially stable
      in mean square. The first multistability criterion is suitable to the case where
      the information on delay derivative is unknown, while the second criterion
      requires that the delay derivative be strictly less than one. For the constant
      delay case, the second multistability criterion is less conservative than the
      first one. Finally, an illustrative example is presented to show the
      effectiveness of the derived results.

PMID- 25988669
TI  - An ultrasensitive sandwich type electrochemiluminescence immunosensor for
      triiodothyronine detection using silver nanoparticle-decorated graphene oxide as
      a nanocarrier.
AB  - An ultrasensitive electrochemiluminescence (ECL) immunosensor was constructed to
      detect 3,3',5-triiodothyronine (T3). The system employed T3-conjugated, silver
      nanoparticle-decorated carboxylic graphene oxide (Ag@fGO-T3) as a carrier and
      anti-T3 antibody-tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)3(2+)) as a probe.
      The Ag@fGO-T3 and Ru(bpy)3(2+) complex could be mobilized rapidly to the anode in
      the reaction chamber through electrophoresis. The fGO is reduced
      electrochemically at the electrode, and the electrons could transfer from an
      anode to the Ru(bpy)3(2+). The complex is excited at the electrode and an ECL
      signal is produced upon reacting with tripropylamine (TPrA). Because of its large
      surface area and excellent conductivity, Ag@fGO could enhance ECL signal
      significantly in the system. Quantitative measurement of T3 could be achieved in
      the range from 0.1 pg/mL to 0.8 ng/mL with a detection limit of 0.05 pg/mL. In
      addition, the novel immunosensor showed good specificity in the presence of
      serum, indicating its high potential in clinical use.

PMID- 25988668
TI  - Specific chemotherapeutic agents induce metastatic behaviour through stromal- and
      tumour-derived cytokine and angiogenic factor signalling.
AB  - Recent studies reveal that chemotherapy can enhance metastasis due to host
      responses, such as augmented expression of adhesion molecules in endothelial
      cells and increased populations of myeloid cells. However, it is still unclear
      how tumour cells contribute to this process. Here, we observed that paclitaxel
      and carboplatin accelerated lung metastasis in tumour-bearing mice, while
      doxorubicin and fluorouracil did not. Mechanistically, paclitaxel and carboplatin
      induced similar changes in cytokine and angiogenic factors. Increased levels of
      CXCR2, CXCR4, S1P/S1PR1, PlGF and PDGF-BB were identified in the serum or primary
      tumour tissues of tumour-bearing mice treated by paclitaxel. The serum levels of
      CXCL1 and PDGF-BB and the tissue level of CXCR4 were also elevated by
      carboplatin. On the other hand, doxorubicin and fluorouracil did not induce such
      changes. The chemotherapy-induced cytokine and angiogenic factor changes were
      also confirmed in gene expression datasets from human patients following
      chemotherapy treatment. These chemotherapy-enhanced cytokines and angiogenic
      factors further induced angiogenesis, destabilized vascular integrity, recruited
      BMDCs to metastatic organs and mediated the proliferation, migration and
      epithelial-to-mesenchymal transition of tumour cells. Interestingly, inhibitors
      of these factors counteracted chemotherapy-enhanced metastasis in both tumour
      bearing mice and normal mice injected intravenously with B16F10-GFP cells. In
      particular, blockade of the SDF-1alpha-CXCR4 or S1P-S1PR1 axes not only
      compromised chemotherapy-induced metastasis but also prolonged the median
      survival time by 33.9% and 40.3%, respectively. The current study delineates the
      mechanism of chemotherapy-induced metastasis and provides novel therapeutic
      strategies to counterbalance pro-metastatic effects of chemo-drugs via
      combination treatment with anti-cytokine/anti-angiogenic therapy.

PMID- 25988670
TI  - European Rabbits as Reservoir for Coxiella burnetii.
AB  - We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir
      for Coxiella burnetii in the Iberian region. High individual and population
      seroprevalences observed in wild and farmed rabbits, evidence of systemic
      infections, and vaginal shedding support the reservoir role of the European
      rabbit for C. burnetii. 

PMID- 25988671
TI  - Nanofiltration to remove microparticles and decrease the thrombogenicity of
      plasma: in vitro feasibility assessment.
AB  - BACKGROUND: As plasma contains procoagulant microparticles (MPs), removing MPs by
      75-nm nanofiltration may decrease plasma in vitro thrombogenicity while
      maintaining the hemostatic activity from coagulation factors. STUDY DESIGN AND
      METHODS: We defined conditions to nanofilter leukoreduced plasma on a 75-nm
      hollow-fiber membrane filter. Plasma quality was assessed by coagulation,
      immunochemical, and electrophoretic assays. MP removal was evaluated by
      biophysical (flow cytometry, dynamic light scattering, nanoparticle tracking
      analysis, and tunable resistive pulse sensing) and functional (thrombin
      generation assay [TGA; Technothrombin], prothrombinase [Zymuphen MP-activity],
      tissue factor [Zymuphen MP-TF], and procoagulant phospholipid-dependent clotting
      time [STA-Procoag-PPL] assays) methods. Spiking experiments using platelet MPs
      were performed to determine extent of removal by nanofiltration. RESULTS: Freshly
      collected leukoreduced, but not previously frozen, plasma could be readily
      nanofiltered on a 0.01-m2 75-nm nanofilter under conditions preserving protein
      and lipoprotein profile, coagulation factor content, and global coagulation
      activity (prothrombin time, activated partial thromboplastin time). Biophysical
      methods confirmed an extensive removal of MPs during nanofiltration. All
      functional assays indicated a marked reduction of plasma in vitro
      thrombogenicity. There was no thrombin generation in nanofiltered plasma tested
      by TGA assay with "RC-low phospholipid concentration" reagent, while it was
      similar to that of starting and leukoreduced plasma samples when using "RC-high
      phospholipid concentration" reagent. More than 9 log of MPs were removed by
      nanofiltration. CONCLUSION: Nanofiltration of 75 nm efficiently removes MPs and
      decreases in vitro thrombogenicity of plasma without affecting the protein
      content or the hemostatic activity of coagulation factors. Studies are needed to
      evaluate the impact of MP removal on in vivo thrombogenic risks and hemostatic
      efficacy.

PMID- 25988672
TI  - Comparison between uroflowmetry and sonouroflowmetry in recording of urinary flow
      in healthy men.
AB  - OBJECTIVES: To evaluate the accuracy of sonouroflowmetry in recording urinary
      flow parameters and voided volume. METHODS: A total of 25 healthy male volunteers
      (age 18-63 years) were included in the study. All participants were asked to
      carry out uroflowmetry synchronous with recording of the sound generated by the
      urine stream hitting the water level in the urine collection receptacle, using a
      dedicated cell phone. From 188 recordings, 34 were excluded, because of voided
      volume <150 mL or technical problems during recording. Sonouroflowmetry recording
      was visualized in a form of a trace, representing sound intensity over time.
      Subsequently, the matching datasets of uroflowmetry and sonouroflowmetry were
      compared with respect to flow time, voided volume, maximum flow rate and average
      flow rate. Pearson's correlation coefficient was used to compare parameters
      recorded by uroflowmetry with those calculated based on sonouroflowmetry
      recordings. RESULTS: The flow pattern recorded by sonouroflowmetry showed a good
      correlation with the uroflowmetry trace. A strong correlation (Pearson's
      correlation coefficient 0.87) was documented between uroflowmetry-recorded flow
      time and duration of the sound signal recorded with sonouroflowmetry. A moderate
      correlation was observed in voided volume (Pearson's correlation coefficient
      0.68) and average flow rate (Pearson's correlation coefficient 0.57). A weak
      correlation (Pearson's correlation coefficient 0.38) between maximum flow rate
      recorded using uroflowmetry and sonouroflowmetry-recorded peak sound intensity
      was documented. CONCLUSIONS: The present study shows that the basic concept
      utilizing sound analysis for estimation of urinary flow parameters and voided
      volume is valid. However, further development of this technology and
      standardization of recording algorithm are required.

PMID- 25988673
TI  - Dielectric and Conduction Mechanisms of Parylene N at High Temperature: Phase
      Transition Effect.
AB  - Dielectric and electrical properties correlated with the structure analysis have
      been studied on 27% semicrystalline parylene-N (-H2C-C6H4-CH2-)n thin films.
      Transition-phase, AC- and DC-conduction mechanisms, and the MW-interfacial
      polarization were identified in parylene N at high temperature by experimental
      and theoretical investigations. The dielectric analysis based on the dc
      conductivity highlights a temperature of 230  degrees C as a transition
      temperature from the alpha-form to the beta1-form. This structure transition is
      accompanied by a modification on the DC-conduction mechanisms from ionic to
      electronic conduction in the alpha-form and the beta1-form, respectively. The AC
      conduction mechanism is governed by the small polaron tunneling mechanism (SPTM)
      with WH,alpha = 0.23 eV and a tunneling distance of 7.71 A in the alpha-form,
      while it becomes a correlated barrier-hopping (CBH) mechanism with a WM,beta 1 =
      0.52 eV in the beta1-form. The imaginary part of the electrical modulus formalism
      obeys the Kohlrausch-Williams-Watt (KWW) model and shows the presence of the
      interfacial polarization effect. The theoretical Kohlrausch exponent (betaKWW)
      confirms the existence of the transition phase on the parylene N in the vicinity
      of the 230  degrees C as deduced by the DC- and the AC-conduction parameters. The
      correlations between the experimental results and the theoretical models are very
      useful knowledge and tools for diverse parylene N applications at high
      temperature. 

PMID- 25988674
TI  - Polyphasic Temporal Behavior of Finger-Tapping Performance: A Measure of Motor
      Skills and Fatigue.
AB  - Successive voluntary motor movement involves a number of physiological mechanisms
      and may reflect motor skill development and neuromuscular fatigue. In this study,
      the temporal behavior of finger tapping was investigated in relation to motor
      skills and fatigue by using a long-term computer-based test. The finger-tapping
      performances of 29 healthy male volunteers were analyzed using linear and
      nonlinear regression models established for inter-tapping interval. The results
      suggest that finger-tapping performance exhibits a polyphasic nature, and has
      several characteristic time points, which may be directly related to muscle
      dynamics and energy consumption. In conclusion, we believe that future studies
      evaluating the polyphasic nature of the maximal voluntary movement will lead to
      the definition of objective scales that can be used in the follow up of some
      neuromuscular diseases, as well as, the determination of motor skills, individual
      ability, and peripheral fatigue through the use of a low cost, easy-to-use
      computer-based finger-tapping test. 

PMID- 25988675
TI  - Overcoming the Fundamental Challenges in Improving the Impact Strength and
      Crystallinity of PLA Biocomposites: Influence of Nucleating Agent and Mold
      Temperature.
AB  - Poly(lactic acid) (PLA), one of the widely studied renewable resource based
      biopolymers, has yet to gain a strong commercial standpoint because of certain
      property limitations. This work is a successful attempt in achieving PLA
      biocomposites that showed concurrent improvements in impact strength and heat
      deflection temperature (HDT). Biocomposites were fabricated from a super
      toughened ternary blend of PLA, poly(ether-b-amide) elastomeric copolymer and
      ethylene-methyl acrylate-glycidyl methacrylate and miscanthus fibers. The effects
      of varying the processing parameters and addition of various nucleating agents
      were investigated. Crystallinity was controlled by optimizing the mold
      temperature and cycle time of the injection process. With the addition of 1 wt %
      aromatic sulfonate derivative (Lak-301) as a nucleating agent at a mold
      temperature of 110  degrees C, PLA biocomposites exhibited dramatic reduction in
      crystallization half time to 1.3 min with crystallinity content of 42%.
      Mechanical and thermal properties assessment for these biocomposites revealed a 4
      fold increase in impact strength compared to neat PLA. The HDT of PLA
      biocomposites increased to 85  degrees C from 55  degrees C compared to neat PLA.
      Crystallization behavior was studied in detail using differential scanning
      calorimetry and was supported with observations from wide-angle X-ray diffraction
      profiles and polarized optical microscopy. The presence of a nucleating agent did
      not alter the crystal structure of PLA; however, a significant difference in
      spherulite size, crystallization rate and content was observed. Fracture surface
      morphology and distribution of nucleating agent in the PLA biocomposites were
      investigated through scanning electron microscopy. 

PMID- 25988677
TI  - Involvement of the Inferior Colliculus in a binaural spatial illusion (Commentary
      on Rajala et al.).

PMID- 25988676
TI  - Safety, tolerability and pharmacokinetics of rilpivirine following administration
      of a long-acting formulation in healthy volunteers.
AB  - OBJECTIVES: This phase I healthy volunteer study (NCT01031589) was carried out to
      investigate the safety/tolerability and pharmacokinetics of a rilpivirine (RPV;
      TMC278) long-acting (LA) formulation after single and multiple intramuscular
      (i.m.) injections. METHODS: In the first part of the study, which had an open
      label design, a single RPV LA i.m. injection (300 mg/mL) of 300 (n = 6) or 600 (n
      = 5) mg was given to the volunteers. In the second part of the study, which had a
      double-blind, randomized, placebo-controlled design, three RPV LA i.m. injections
      (one every 4 weeks) at 1200/600/600 mg (n = 6) or placebo (n = 2) were given.
      Safety and local tolerability were monitored. RPV plasma concentrations were
      analysed up to 28 days after injection or until they were < 20 ng/mL. RESULTS:
      Grade 1/2 RPV-related adverse events in the 300, 600 and 1200/600/600 mg groups
      were: rash (zero, one and one subject, respectively, the last of whom
      discontinued participation in the study); musculoskeletal stiffness (three, zero
      and zero subjects, respectively); injection site reactions (one, two and two
      subjects, respectively). After one injection of 300, 600 or 1200 mg RPV LA, the
      mean (standard deviation) maximum plasma concentration was 39 (25), 48 (13) and
      140 (16) ng/mL, and the mean (standard deviation) area under the concentration
      time curve (28 days) was 17,090 (8907), 25,240 (8184) and 55,350 (13,550) ng
      h/mL, respectively. RPV pharmacokinetics were largely comparable after the 1200
      mg loading dose and both 600 mg injections of RPV LA. The mean (standard
      deviation) RPV plasma concentration across the 28-day dosing interval after the
      last injection in the 1200/600/600 mg group was 79 (19) ng/mL. CONCLUSIONS:
      Single and multiple i.m. injections of RPV LA demonstrated favourable
      local/systemic tolerability in healthy volunteers. RPV pharmacokinetics suggested
      that clinically relevant plasma concentrations can be achieved with this LA
      formulation.

PMID- 25988678
TI  - Canine brain tumours: a model for the human disease?
AB  - Canine brain tumours are becoming established as naturally occurring models of
      disease to advance diagnostic and therapeutic understanding successfully. The
      size and structure of the dog's brain, histopathology and molecular
      characteristics of canine brain tumours, as well as the presence of an intact
      immune system, all support the potential success of this model. The limited
      success of current therapeutic regimens such as surgery and radiation for dogs
      with intracranial tumours means that there can be tremendous mutual benefit from
      collaboration with our human counterparts resulting in the development of new
      treatments. The similarities and differences between the canine and human
      diseases are described in this article, emphasizing both the importance and
      limitations of canines in brain tumour research. Recent clinical veterinary
      therapeutic trials are also described to demonstrate the areas of research in
      which canines have already been utilized and to highlight the important potential
      benefits of translational research to companion dogs.

PMID- 25988679
TI  - Poor Efficiency of Eight-Plates in the Treatment of Lower Limb Discrepancy.
AB  - BACKGROUND: Among the numerous existing epiphysiodesis procedures, the eight
      plate-guided growth technique, initially described for angular deformities
      correction, has progressively gained popularity among pediatric orthopaedic
      surgeons to treat lower limb discrepancy (LLD). The goal of this study was to
      assess the efficacy of eight-plates in LLD. METHODS: All children treated for LLD
      with eight-plates were prospectively included and followed until skeletal
      maturity. Efficacy of the epiphysiodesis was calculated 6 and 18 months
      postoperatively and at latest follow-up, according to a method previously
      validated for percutaneous epiphysiodesis using transphyseal screws (PETS).
      Radiologic measurements were performed using 3-dimensional low-dose
      stereoradiography. Intraoperative and postoperative complications were reported.
      RESULTS: Thirty-two patients were included (average age at surgery, 12.5 y). For
      femoral epiphysiodesis, efficacy was only 23% at 6 months and 68% at latest
      follow-up. The procedure was even less efficient on the proximal tibia, with only
      42% of the expected growth arrest at latest examination. Eight patients (20%)
      experienced plate-related pain during follow-up, and 5 physes (12.5%) required
      unplanned revision surgery. CONCLUSIONS: Results of the current series show that
      the eight-plate technique procedure was associated with few perioperative
      complications, but the growth arrest observed at follow-up was unpredictable and
      lower than that achieved with PETS in previous reports. Eight-plate procedures
      cannot be considered as an efficient epiphysiodesis technique in comparison with
      standard technique. LEVEL OF EVIDENCE: Level IV.

PMID- 25988680
TI  - Intercondylar Notch Width as a Risk Factor for Medial Femoral Condyle
      Osteochondritis Dissecans in Skeletally Immature Patients.
AB  - BACKGROUND: Juvenile osteochondritis dissecans (OCD) of the medial femoral
      condyle (MFC) is one of the most common causes of knee pain in adolescents.
      Wilson sign reproduces knee pain with internal rotation of the tibia during
      extension of the knee from 90 to 30 degrees due to impingement of the tibial
      eminence on the MFC. This impingement may result in microtrauma and contribute to
      lesion formation. The purpose of this study was to evaluate anatomic factors that
      may increase the likelihood of impingement by using magnetic resonance imaging
      scans of patients with MFC OCD lesions to measure tibial eminence height and
      femoral notch width. METHODS: A retrospective, case-control study was performed
      using the radiology database at our institution between July 2009 and February
      2014. Magnetic resonance imagings of patients with MFC OCD lesions and matched
      controls were identified. For each patient, tibial eminence height and femoral
      notch width were measured and then normalized for patient size [creating the
      tibial eminence height normalized, and the notch width index (NWI),
      respectively]. Values for OCD and control knees were compared using Student t
      test. Interrater and intrarater reliability were calculated using intraclass
      correlation coefficients. RESULTS: Thirty-five MFC OCD patients and matched
      controls were identified. Comparison of the groups showed a significantly smaller
      NWI in MFC OCD knees than in the matched controls (0.2620+/-0.0248 vs. 0.2886 +/
      0.0323, P=0.0003). There was no difference in tibial eminence height normalized
      between groups (0.1387+/-0.0161 vs. 0.1428+/-0.0108, P=0.21). Interrater and
      intrarater reliability of all measurements was good to excellent (0.81 to 1.00)
      when measurements were made using bony margins. CONCLUSIONS: Knees with MFC OCD
      lesions have significantly smaller NWIs than matched controls. This anatomic
      factor may increase the likelihood of tibial eminence impingement and contribute
      to OCD lesion formation. LEVEL OF EVIDENCE: Level III-case-control study.

PMID- 25988682
TI  - Fatal bacteremia caused by Campylobacter gracilis, United States.

PMID- 25988683
TI  - Observation and Mediation of the Presence of Metallic Lead in Organic-Inorganic
      Perovskite Films.
AB  - We have employed soft and hard X-ray photoelectron spectroscopies to study the
      depth-dependent chemical composition of mixed-halide perovskite thin films used
      in high-performance solar cells. We detect substantial amounts of metallic lead
      in the perovskite films, which correlate with significant density of states above
      the valence band maximum. The metallic lead content is higher in the bulk of the
      perovskite films than at the surface. Using an optimized postanneal process in
      air, we can reduce the metallic lead content in the perovskite film. This process
      reduces the amount of metallic lead and a corresponding increase in the
      photoluminescence quantum efficiency of the perovskite films can be observed.
      This correlation indicates that metallic lead impurities are likely a key defect
      whose concentration can be controlled by simple annealing procedures in order to
      increase the performance for perovskite solar cells. 

PMID- 25988684
TI  - Post-traumatic Stress Symptoms among Iranian Parents of Children during Cancer
      Treatment.
AB  - Support of parents of children with cancer requires healthcare personnel to be
      knowledgeable about the prevalence of post-traumatic stress symptoms among
      Iranian parents of children with cancer. This study was conducted to fulfill this
      aim in the South-East of Iran. Using the Impact of Event Scale -Revised, for
      parents of children with cancer, 200 parents in two hospitals supervised by
      Kerman University of Medical Sciences, were assessed. The total mean score of
      post-traumatic stress symptoms was 41.70. Among all categories of the Impact of
      Event Scale -Revised, the highest mean belonged to the category of 'intrusion'
      16.03 (SD  =  6.24) and the lowest one belonged to the category of 'hyperarousal'
      10.68 (SD  =  4.58). Based on the results, mothers had higher post-traumatic
      stress symptoms compared with fathers (p < 0.05). Adjusted odds ratio showed that
      the prevalence of post-traumatic stress symptoms among mothers was 2.49 times
      more than that among fathers (p  =  0.01). There was no association between
      sociodemographic data and post-traumatic stress symptoms. More research is needed
      to elucidate the Iranian parents' experience of having children with cancer. 

PMID- 25988681
TI  - Partially Digested Adult Cardiac Extracellular Matrix Promotes Cardiomyocyte
      Proliferation In Vitro.
AB  - Stimulating or maintaining the proliferative capacity of postnatal mammalian
      cardiomyocytes is a major challenge to cardiac regeneration. Previously, it is
      found that fetal cardiac extracellular matrix (ECM) can promote neonatal rat
      cardiomyocyte proliferation in vitro better than neonatal or adult ECM. It is
      hypothesized that partial digestion of adult ECM (PD-ECM) would liberate less
      crosslinked components that promote cardiomyocyte proliferation, similar to fetal
      ECM. Neonatal rat cardiac cells are seeded onto substrates coated with adult rat
      cardiac ECM that has been solubilized in pepsin-HCl for 1, 3, 6, 12, 24, or 48 h.
      Cardiomyocyte proliferation and fold-change in numbers from 1 to 5 d are highest
      on 1 and 3 h PD-ECM compared to other conditions. Sarcomeres tend to mature on 24
      and 48 h PD-ECM where low proliferation is observed. 3 h PD-ECM is primarily
      composed of Fibrillin-1, Fibrinogen, and Laminins while 48 h PD-ECM is dominated
      by Collagen I. Our results suggest that adult ECM retains regenerative cues that
      may be masked by more abundant, mature ECM components. PD-ECM provides a simple
      yet powerful approach to promoting cardiomyocyte proliferation. 

PMID- 25988685
TI  - Mucocele of the tongue.

PMID- 25988686
TI  - Impact of modernization on adult body composition on five islands of varying
      economic development in Vanuatu.
AB  - OBJECTIVE: The Republic of Vanuatu, similar to other South Pacific island
      nations, is undergoing a rapid health transition as a consequence of
      modernization. The pace of modernization is uneven across Vanuatu's 63 inhabited
      islands, resulting in differential impacts on overall body composition and
      prevalence of obesity among islands, and between men and women. In this study, we
      investigated (1) how modernization impacts body composition between adult male
      and female Melanesians living on four islands of varying economic development in
      Vanuatu, and (2) how body composition differs between adult Melanesians and
      Polynesians living on rural islands in Vanuatu. METHODS: Anthropometric
      measurements were taken on adult male and female Melanesians aged 18 years and
      older (n = 839) on the islands of Ambae (rural), Aneityum (rural with tourism),
      Nguna (rural with urban access), and Efate (urban) in Vanuatu, in addition to
      Polynesian adults on Futuna (rural). RESULTS: Mean measurements of body mass and
      fatness, and prevalence of obesity, were greatest on the most modernized islands
      in our sample, particularly among women. Additionally, differences between men
      and women became more pronounced on islands that were more modernized. Rural
      Polynesians on Futuna exhibited greater body mass, adiposity, and prevalence of
      obesity than rural Melanesians on Ambae. CONCLUSIONS: We conclude that Vanuatu is
      undergoing an uneven and rapid health transition resulting in increased
      prevalence of obesity, and that women are at greatest risk for developing obesity
      related chronic diseases in urbanized areas in Vanuatu.

PMID- 25988688
TI  - What defines a high-volume hip or knee surgeon in the United States?
AB  - The literature suggests that high-volume hip and knee surgeons have better
      patient outcomes. Therefore, clearly defining a high-volume or a low-volume
      surgeon is important. The definition of high-volume has been quite arbitrary, and
      numbers such as 50 surgeries per year have been used to define high-volume. The
      objective of this study was to show that, on the basis of data contained in the
      National Inpatient Sample database, using the quartile approach will quantify the
      increasing number of surgeries required per year to remain a high-volume joint
      surgeon. Using quartiles may provide a more consistent way to define what is
      meant by a low- or high-volume surgeon in the United States, and a clear
      definition of quartiles will aid future studies seeking to determine whether
      outcomes can be correlated with quartiles. 

PMID- 25988687
TI  - Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and
      low morbidity in the general population: A long-term follow-up study, the WHO
      MONICA project, Gothenburg, Sweden.
AB  - OBJECTIVE: There is limited knowledge about the natural history of
      normocalcaemic, vitamin D-sufficient hyperparathyroidism (nHPT). The aim was to
      study the prevalence of nHPT and its relation to morbidity. DESIGN: Cross
      sectional and retrospective study at the Sahlgrenska University Hospital,
      Gothenburg, Sweden. SUBJECTS: A random population of 608 men and women, age 25-64
      years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in
      2008 (n = 410, of whom 277 were vitamin D sufficient). MEASUREMENTS: A serum
      intact parathyroid hormone (S-PTH) >=60 ng/l was considered as HPT, S-calcium
      2.15-2.49 mmol/l as normocalcaemia and S-25(OH)D >= 50 nmol/l as vitamin D
      sufficiency. Data on fractures, stroke and myocardial infarction were retrieved
      until 2013, that is a 17-year follow-up. RESULTS: The prevalence of nHPT was 2.0%
      in 1995 (age 25-64) and 11.0% in 2008 (age 38-79). S-PTH was positively
      correlated with age and BMI. After adjustment for these variables, a high S-PTH
      level (>=60 ng/l) at follow-up was associated with previously low S-25(OH)D, high
      osteocalcin, S-PTH and both past and presently treated hypertension. No relation
      was seen with creatinine, cystatin C, malabsorption markers, thyroid function,
      glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures,
      myocardial infarction, stroke or death at follow-up. CONCLUSIONS: This small
      random population study showed that nHPT was common, 11% at follow-up. Only one
      individual developed mild hypercalcaemia in 13 years. Previous S-PTH was
      predictive of nHPT and hypertension was prevalent, but no increase in hard end
      points was seen over a 17-year period.

PMID- 25988689
TI  - Proton therapy for prostate cancer: why and what orthopaedic surgeons need to
      know about it.
AB  - Most orthopaedic surgeons are unfamiliar with proton therapy or the difference
      between proton radiation and photon (X-ray) radiation. After they perform a total
      hip replacement or metallic hip implant, their patient cannot have proton therapy
      for prostate cancer because the protons must pass exclusively through the hips
      and are blocked by metal. Proton therapy is a sophisticated and expensive
      technology with growing demand and limited supply. In proton therapy, heavy
      protons are accelerated to almost the speed of light in a synchrotron (particle
      accelerator) down a magnetic beam the length of a football field to radiate
      cancers. Proton therapy is a remarkably safe and effective treatment for prostate
      cancer, the most common cancer in men, although treatment superiority has yet to
      be proved in randomized studies. There are currently only 10 proton centers in
      the United States. 

PMID- 25988690
TI  - Total hip arthroplasty in very young bone marrow transplant patients.
AB  - Concerns remain about total hip arthroplasty (THA) performed in very young
      patients, especially those with complex medical history such as allogeneic bone
      marrow transplantation (ABMT). This study retrospectively reviews the
      perioperative courses and functional outcomes of ABMT patients <21 years old
      undergoing primary uncemented THA. Nine THAs were performed in five ABMT patients
      at an average age of 19.7 years. The interval between ABMT and THA was 73.0
      months with clinical follow-up of 25.8 months. Harris Hip Scores (HHS) increased
      dramatically from preoperatively 44.5 (range, 31.1-53.4) to postoperatively 85.2
      (range, 72.0-96.0) and all patients subjectively reported a good (four hips) to
      excellent (five hips) overall outcome. There was one reoperation for
      periprosthetic fracture fixation but there were no infections or revisions
      performed. Despite the history of severe hematopoietic conditions requiring ABMT,
      these very young patients do appear to have improved pain and function following
      primary THA with short-term follow-up. 

PMID- 25988691
TI  - Outcomes of biceps tenodesis in an active duty population.
AB  - Pathology affecting the long head of the biceps tendon and its insertion is a
      frequent cause of shoulder pain in the active duty military population. The
      purpose of this investigation was to evaluate functional outcomes of subpectoral
      biceps tenodesis in an active duty population. A retrospective case series of 22
      service members who underwent biceps tenodesis was performed and Shoulder Pain
      and Disability Indexes (SPADI) and Disabilities of the Arm, Shoulder and Hand
      (DASH) scores were obtained preoperatively and at 6 months. Additionally, a
      review of each subject's physical profile was performed 6 months after surgery to
      determine continued physical limitations and one's ability to deploy. There was a
      statistically significant improvement in SPADI and DASH scores comparing
      preoperative versus postoperative outcomes. Although five subjects (22%)
      continued to have a restriction to performing push-ups on the Army Physical
      Fitness Test, all were deemed deployable from a physical standpoint. The results
      of this review suggest that active duty personnel undergoing biceps tenodesis
      have significant functional improvement at 6 months. Additionally, very few have
      long-term physical limitations or deployment restrictions. 

PMID- 25988692
TI  - Utility of computed tomography arthrograms in evaluating osteochondral allograft
      transplants of the distal femur.
AB  - Postsurgical evaluation of osteochondral allograft transplant surgery (OATS) of
      the distal femur most commonly utilizes radiographs or magnetic resonance
      imaging. This article proposes the utilization of computed tomography (CT)
      arthrography as an additional option, which allows clear assessment of articular
      congruity and osseous integration. A retrospective review was performed of 18
      patients who underwent an OATS for distal femoral chondral lesions and obtained
      CT arthrograms postoperatively. CT arthrograms were evaluated for osseous
      integration and articular congruity. The average age and follow-up were 30.9
      years and 4.3 years, respectively. Only 60% of patients were able to remain in
      the military postoperatively. The articular cartilage was smooth in eight
      (44.4%); complete bony integration was noted in eight (44.4%) patients. Neither
      articular congruity nor bony integration was associated with duty status at final
      follow-up. Although it allows excellent evaluation, similar to other modalities,
      CT arthrogram does not appear predictive of functional outcome. 

PMID- 25988694
TI  - Army orthopaedic surgery residency program directors' selection criteria.
AB  - Factors associated with successful selection in U.S. Army orthopaedic surgical
      programs are unreported. The current analysis includes survey data from all Army
      orthopaedic surgery residency program directors (PDs) to determine these factors.
      PDs at all Army orthopaedic surgery residency programs were provided 17 factors
      historically considered critical to successful selection and asked to rank order
      the factors as well as assign a level of importance to each. Results were
      collated and overall mean rankings are provided. PDs unanimously expressed that
      performance during the on-site orthopaedic surgery rotation at the individual
      program director's institution was most important. Respondents overwhelmingly
      reported that Steps 1 and 2 licensing exam scores were next most important,
      respectively. Survey data demonstrated that little importance was placed on
      letters of recommendation and personal statements. PDs made no discriminations
      based on allopathic or osteopathic degrees. The most important factors for Army
      orthopaedic surgery residency selection were clerkship performance at the
      individual PD's institution and licensing examination score performance. Army PDs
      consider both USMLE and COMLEX results, because Army programs have a higher
      percentage of successful osteopathic applicants. 

PMID- 25988693
TI  - Uninterrupted perioperative clopidogrel and bleeding-related events after total
      joint arthroplasty: a case series.
AB  - There is a known bleeding risk with administration of the antiplatelet drug
      clopidogrel, but in certain patients the likelihood of thrombosis is too high to
      cease its administration perioperatively. The risks of performing total joint
      arthroplasty in this population are unknown. An inpatient pharmacy database query
      identified seven patients who underwent eight hip or knee arthroplasties from
      2007 to 2009 without perioperative interruption in clopidogrel administration.
      Bleeding-related events were recorded, including one inpatient death, one
      reoperation for infection, two 30-day readmissions, two antibiotic prescriptions
      for the incision, and blood transfusion administration during seven of eight
      admissions. The majority of bleeding-related events occurred following knee
      arthroplasty. Uninterrupted perioperative clopidogrel administration was
      associated with a high risk of bleeding-related events following total joint
      arthroplasty, particularly of the knee. Consideration should be given to delaying
      total joint arthroplasty until clopidogrel can safely be held in the
      perioperative period. 

PMID- 25988696
TI  - Reverse oblique end screws in nonlocking plates decrease construct strength in
      synthetic osteoporotic bone medium.
AB  - Fracture stability can be challenging for osteoporotic individuals. The end screw
      of nonlocked plates is subjected to the greatest loading and is typically the
      site of construct failure. To enhance fixation, the end screw can be angled away
      from the fracture. The current study biomechanically evaluated screws angled the
      other direction: toward the fracture using 3.5-mm dynamic compression plates in
      an osteoporotic bone model. Three different plate lengths (6-, 8-, 12-hole) were
      tested in three-point bending with an oblique, perpendicular, or reverse oblique
      end screw. The peak load for loss of screw fixation for the reverse oblique end
      screw constructs was significantly less than the other screw orientations for all
      plate lengths. The 12-hole peak load, energy, and displacement magnitudes for all
      three screw orientations were significantly greater than all 6- and 8-hole
      constructs. The use of a reverse oblique end screw is inferior to both
      perpendicular and oblique end screws. 

PMID- 25988695
TI  - Return to driving after arthroscopic rotator cuff repair: patient-reported safety
      and maneuverability.
AB  - This survey investigated patients' return to driving after rotator cuff surgery,
      to determine whether pain, weakness, sling use, and narcotics correlate with self
      assessed safety and maneuvering. Fifty-four patients (80.6% of those eligible)
      were surveyed 4 months after surgery. Return to driving ranged widely from same
      day to 4 months, with two not driving at 4 months; 12% reported narcotics use and
      33% reported sling use. Drivers reporting weakness were more likely to feel
      unsafe (p = .02) and more likely to report difficulty maneuvering (p <.01).
      Drivers reporting pain were more likely to feel unsafe (p < .01) and more likely
      to report difficulty maneuvering their vehicle (p < .01). Patient-reported return
      to driving does not correspond to perceived safety; pain and weakness correspond
      with feeling unsafe and difficulty maneuvering. Although subjective, clinicians
      may find these self-assessments predictive when counseling patients on return to
      driving. 

PMID- 25988697
TI  - Stem pain after cementless revision total knee arthroplasty.
AB  - Revision total knee arthroplasty (TKA) often requires long diaphyseal supporting
      stems. Pain at the end of the cemented revision stem has been reported, but no
      study has been published regarding the incidence in cementless revision TKA. This
      study reviewed 120 cementless revision TKAs with a diaphyseal slotted stem to
      compare the incidence of stem pain to that in a control cohort of 100 primary TKA
      patients with a metaphyseal stem. In the revision cohort, 20 out of 120 patients
      reported pain at the end of their stem on the tibia, but no patient reported
      thigh pain. In the primary TKA cohort, seven out of 100 patients reported pain
      below the tibial stem. No correlation between stem length or stem fit was found.
      This study found that more than 16% of patients may have pain at the end of their
      press-fit revision TKA stem, and this complication should be explained to
      patients before their revision TKA surgery. 

PMID- 25988698
TI  - Scapholunate advanced collapse.
AB  - This case study reviews the pathophysiology of scapholunate advanced collapse
      (SLAC), which is the most common etiology of degenerative arthritis in the wrist.
      The scapholunate ligament serves a critical role in stability of the carpus.
      Disruption of the scapholunate ligament, its sequela, and the magnetic resonance
      imaging evaluation are discussed, with review of the defining features of this
      disease and its progression. 

PMID- 25988699
TI  - Free vascularized fibular grafts for femoral head osteonecrosis: alternative
      technique utilizing a buttress plate for graft fixation.
AB  - Core decompression with free vascularized fibular grafting is an effective hip
      preservation treatment for osteonecrosis of the femoral head. This procedure has
      traditionally utilized a single Kirschner wire to secure the fibular strut within
      the femoral neck. While this method has proven effective, migration of the
      Kirschner wire remains the most common recipient site complication. Additionally
      the presence of the Kirschner wire traversing the intramedullary canal can also
      complicate future hip arthroplasty. Therefore, this article describes a simple
      graft fixation technique utilizing a buttress plate that obviates migration
      problems. Ten patients are presented with at least 6 months of follow-up who have
      been treated with this technique without complications. This fixation method is
      simple and eliminates a major potential complication and allows for easier
      conversion to total hip arthroplasty. 

PMID- 25988700
TI  - Use of the lateral fluoroscopic view to identify a safe starting point and
      trajectory lines when placing percutaneous iliosacral screws.
AB  - Safe percutaneous placement of iliosacral screws remains a challenge given the
      close proximity to neurovascular structures. Because of the concerns with safe
      placement, surgeons have explored the use of three-dimensional fluoroscopy and
      intraoperative computed tomography-guided screw placement with success; however,
      these intraoperative aids are not readily available and, in some cases, are cost
      prohibitive. The authors present a surgical technique that varies from the
      standard technique for placement of percutaneous iliosacral screws by utilizing
      the lateral sacral view at the start of the procedure to identify the appropriate
      starting point and trajectory lines, which aid in obtaining fluoroscopic imaging
      and guiding pin advancement. Use of this technique has resulted in the safe
      placement (no cortical breach) of 97.5% of iliosacral screws. 

PMID- 25988701
TI  - Leishmania survival in the macrophage: where the ends justify the means.
AB  - Macrophages are cells of the immune system that mediate processes ranging from
      phagocytosis to tissue homeostasis. Leishmania has evolved ingenious ways to
      adapt to life in the macrophage. The GP63 metalloprotease, which disables key
      microbicidal pathways, has recently been found to disrupt processes ranging from
      antigen cross-presentation to nuclear pore dynamics. New studies have also
      revealed that Leishmania sabotages key metabolic and signaling pathways to fuel
      parasite growth. Leishmania has also been found to induce DNA methylation to turn
      off genes controlling microbicidal pathways. These novel findings highlight the
      multipronged attack employed by Leishmania to subvert macrophage function. 

PMID- 25988702
TI  - Oxygen sensing by protozoans: how they catch their breath.
AB  - Cells must know the local levels of available oxygen and either adapt accordingly
      or relocate to more favorable environments. Prolyl 4-hydroxylases (P4Hs) are
      emerging as universal cellular oxygen sensors. In animals, these oxygen sensors
      respond to decreased oxygen availability by up-regulating hypoxia-inducible
      transcription factors. In protozoa, the P4Hs appear to activate E3-SCF ubiquitin
      ligase complexes via a glycosylation-dependent mechanism, potentially to turn
      over their proteomes. Intracellular parasites are impacted by both types of
      oxygen-sensing pathways. Since parasites are exposed to diverse oxygen tensions
      during their life cycles, this review identifies emerging oxygen-sensing
      mechanisms and discusses how these mechanisms probably contribute to the
      regulation of unicellular eukaryotes. 

PMID- 25988703
TI  - Bullying victimization in childhood predicts inflammation and obesity at mid
      life: a five-decade birth cohort study.
AB  - BACKGROUND: We aimed to test whether childhood bullying victimization increases
      risk for age-related disease at mid-life using biological markers including
      inflammation and adiposity, independent of other childhood risk factors and key
      adult variables. METHOD: The present study was a 50-year prospective longitudinal
      birth cohort study of all births in Britain in 1 week in 1958. Exposure to
      bullying was assessed prospectively when participants were aged 7 and 11 years
      (27.7% occasionally bullied; 14.6% frequently bullied). Blood inflammation
      biomarkers [C-reactive protein (CRP) and fibrinogen] and adiposity [body mass
      index (BMI) and waist:hip ratio] were measured at age 45 years. RESULTS:
      Participants who had been frequently bullied in childhood showed increased levels
      of CRP at mid-life [beta = 0.07, 95% confidence interval (CI) 0.04-0.10] and
      higher risk for clinically relevant inflammation cut-off [CRP > 3 mg/l: 20.4% v.
      15.9%, odds ratio (OR) = 1.35, 95% CI 1.12-1.64]. Women who were bullied in
      childhood had higher BMI than non-bullied participants and were at increased risk
      of being obese (BMI >= 30 kg/m2: occasionally bullied: 26.0% v. 19.4%, OR = 1.45,
      95% CI 1.18-1.77; frequently bullied: 26.2% v. 19.4%, OR = 1.41, 95% CI 1.09
      1.83). Findings remained significant when controlling for childhood risk factors
      (e.g. parental social class; participants' BMI and psychopathology in childhood)
      and key adult variables (e.g. adult social class, smoking, diet and exercise).
      CONCLUSIONS: Bullied children show increases in risk factors for age-related
      disease in middle adulthood, independent of co-occurring childhood and adult
      risks. Given the high prevalence of bullying victimization in childhood, tackling
      this form of psychosocial stress early in life has the potential of reducing risk
      for age-related disease and its associated burden.

PMID- 25988704
TI  - Characterization of polymeric nanomaterials using analytical ultracentrifugation.
AB  - The characterization of nanomaterials represents a complex analytical challenge
      due to their dynamic nature (small size, high reactivity, and instability) and
      the low concentrations in the environment, often below typical analytical
      detection limits. Analytical ultracentrifugation (AUC) is especially useful for
      the characterization of small nanoparticles (1-10 nm), which are often the most
      problematic for the commonly used techniques such as electron microscopy or
      dynamic light scattering. In this study, small polymeric nanomaterials
      (allospheres) that are used commercially to facilitate the distribution of
      pesticides in agricultural fields were characterized under a number of
      environmentally relevant conditions. Under most of the studied conditions, the
      allospheres were shown to have a constant hydrodynamic diameter (dH) of about 7.0
      nm. Only small increases in diameter were observed, either at low pH or very high
      ionic strength or hardness, demonstrating their high physicochemical stability
      (and thus high mobility in soils). Furthermore, natural organic matter had little
      effect on the hydrodynamic diameters of the allospheres. The concentration of the
      nanoparticles was an important parameter influencing their agglomeration-results
      obtained using dynamic light scattering at high particle concentrations showed
      large agglomerate sizes and significant particle losses through sedimentation,
      clearly indicating the importance of characterizing the nanomaterials under
      environmentally relevant conditions.

PMID- 25988706
TI  - Anti-RNA Polymerase II Antibodies in a U.S. Cohort of Systemic Sclerosis
      Patients: Comment on the Article by Hamaguchi et al.

PMID- 25988705
TI  - Determining the Minimally Important Difference in the Clinical Disease Activity
      Index for Improvement and Worsening in Early Rheumatoid Arthritis Patients.
AB  - OBJECTIVE: Simplified measures to quantify rheumatoid arthritis (RA) disease
      activity are increasingly used. The minimum clinically important differences
      (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI),
      have not been well-defined in real-world clinic settings, especially for early RA
      patients with low/moderate disease activity. METHODS: Data from Canadian Early
      Arthritis Cohort patients were used to examine absolute change in CDAI in the
      first year after enrollment, stratified by disease activity. MCID cut points were
      derived to optimize the sum of sensitivity and specificity versus the gold
      standard of patient self-reported improvement or worsening. Sensitivity,
      specificity, positive predictive values, and negative predictive values were
      calculated against patient self-reported improvement (gold standard) and for
      change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score
      in 28 joints (DAS28) improvement. Discrimination was examined using the area
      under receiver operator curves. Similar methods were used to evaluate MCIDs for
      worsening for patients who achieved low disease activity. RESULTS: A total of 578
      patients (mean +/- SD age 54.1 +/- 15.3 years, 75% women, median [interquartile
      range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to
      the improvement analysis. The MCID cut points for improvement were 12 (patients
      starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10-22), and 1
      (low disease activity: CDAI <10). Performance characteristics were acceptable
      using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening
      among patients who achieved low disease activity was 2 units. CONCLUSION: These
      minimum important absolute differences in CDAI can be used to evaluate
      improvement and worsening and increase the utility of CDAI in clinical practice.

PMID- 25988707
TI  - The association between the RAGE G82S polymorphism, sRAGE and chronic
      periodontitis in Taiwanese individuals with and without diabetes.
AB  - BACKGROUND AND OBJECTIVE: The present study investigated the association between
      the RAGE G82S polymorphism, the plasma levels of sRAGE and chronic periodontitis
      in subjects with and without diabetes mellitus (DM). MATERIAL AND METHODS: A
      total of 230 patients with DM and 264 non-DM participants were recruited for this
      study. Genotyping of the RAGE G82S polymorphism was accomplished using polymerase
      chain reaction-restriction fragment length polymorphism, and associations were
      analyzed with the chi-squared test and logistic regression analysis. RESULTS: In
      the non-DM group, the chi-squared test showed that the frequency distributions of
      the G82S polymorphism were significantly different between chronic periodontitis
      and non-chronic periodontitis subjects (chi(2) = 8.39, p = 0.02). A multivariate
      logistic regression model showed that the (G82S + S82S) genotypes were associated
      with a significantly increased risk of chronic periodontitis development compared
      to the G82G genotype (adjusted odds ratio = 2.06, 95% confidence interval: 1.08
      4.07). In the DM group, there was no association between the G82S polymorphism
      and chronic periodontitis development when a multivariate logistic regression was
      performed. Plasma levels of sRAGE were significantly higher in subjects with the
      G82G genotype compared to those with the (G82S + S82S) genotypes in both the non
      DM (856.6 +/- 332.0 vs. 720.4 +/- 311.4 pg/mL, p = 0.003) and DM groups (915.3 +/
      497.1 vs. 603.5 +/- 298.3 pg/mL, p < 0.0001). However, there was no difference
      in plasma sRAGE levels between chronic periodontitis and non-chronic
      periodontitis subjects in both the DM and non-DM groups. Moreover, when the
      subjects were further sub-divided by the G82S polymorphism, the difference in
      plasma levels of sRAGE between chronic periodontitis and non-chronic
      periodontitis subjects in the DM and non-DM groups remained statistically
      insignificant. CONCLUSIONS: The present study revealed that the RAGE G82S
      polymorphism was associated with chronic periodontitis in the non-DM group but
      not in the DM group. Our results also showed that the plasma levels of sRAGE were
      significantly higher in subjects with the RAGE G82G genotype, and this
      correlation was not affected by the presence of chronic periodontitis in the DM
      and non-DM groups.

PMID- 25988708
TI  - Using Transdermal Alcohol Monitoring to Detect Low-Level Drinking.
AB  - BACKGROUND: Several studies demonstrate the utility of Alcohol Monitoring
      Systems' (AMS) transdermal alcohol concentration (TAC) monitor to objectively
      quantify drinking. AMS standard criteria (i.e., TAC >0.02 g/dl) used for drinking
      detection are deliberately conservative, but consequently only detect drinking
      equivalent to 5 or more standard drinks. Our study sought to characterize the
      sensitivity of TAC measurement to detect low-level drinking defined as the
      consumption of 1 to 3 beers. METHODS: Data were pooled from 3 studies giving
      controlled doses of 1, 2, 3, 4, and 5 Corona(c) beers (12 oz = 0.92 standard
      units) to 32 male and 29 female research volunteers wearing TAC monitors under
      controlled conditions. Analyses describe the sensitivity to detect drinking at
      various peak TAC thresholds beginning with any positive reading >0 g/dl, and then
      using TAC thresholds of 0.02 and 0.03 g/dl. RESULTS: Nearly 40% of participants
      drinking 1 beer did not have a positive TAC reading. However, positive TAC
      readings were observed in more than 95 and in 100% of participants drinking 2 and
      3 or more beers, respectively. The probability of peak TAC detection was a
      positive function of the number of beers consumed and a negative function of the
      minimum TAC threshold for detection. Drinking was somewhat more likely to be
      detected in females than males drinking 2 to 5 beers, but not after 1 beer. Use
      of AMS standard criteria only reliably detected the consumption of 5 beers, and
      45.9% of all occasions of drinking 1 to 3 beers were undetected using 0.02 g/dl
      as a threshold. CONCLUSIONS: Peak TAC levels between 0 and 0.02 g/dl must be
      considered to detect the low-level drinking of 1 to 3 standard drinks, and such
      thresholds are necessary when researchers and clinicians want to detect low-level
      drinking.

PMID- 25988709
TI  - Enhanced emission of charged-exciton polaritons from colloidal quantum dots on a
      SiN/SiO2 slab waveguide.
AB  - We investigate the photoluminescence (PL) spectra and the time-resolved PL decay
      process from colloidal quantum dots on SiN/SiO2 wet etched via BOE (HF:NH4F:H2O).
      The spectrum displays multi-peak shapes that vary with irradiation time. The
      evolution of the spectral peaks with irradiation time and collection angle
      demonstrates that the strong coupling of the charged-exciton emission to the
      leaky modes of the SiN/SiO2 slab waveguide predominantly produces short
      wavelength spectral peaks, resulting in multi-peak spectra. We conclude that BOE
      etching enhances the charged-exciton emission efficiency and its contribution to
      the total emission compared with the unetched case. BOE etching smoothes the
      electron confinement potential, thus decreasing the Auger recombination rate.
      Therefore, the charged-exciton emission efficiency is high, and the charged
      exciton-polariton emission can be further enhanced through strong coupling to the
      leaky mode of the slab waveguide. 

PMID- 25988711
TI  - Patient-perceived benefit of sialendoscopy as measured by the Glasgow Benefit
      Inventory.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate the patient-perceived effect of sialendoscopy on
      patients with obstructive symptoms from the salivary glands. STUDY DESIGN:
      Retrospectively identified cohort used for a prospective study of all consecutive
      patients at the Department of Otorhinolaryngology at Vejle Hospital, Vejle,
      Denmark, March 2009 to December 2013. METHODS: By chart review we recorded the
      patient's age, gender, date of the sialendoscopy, type of gland, sialolithiasis,
      successful extraction of sialolithiasis, stenosis of salivary ducts, dilation,
      type of saliva, and surgeon. The follow-up was done by applying the Glasgow
      Benefit Inventory questionnaire by letter and telephone. RESULTS: There were 130
      sialendoscopies performed on 116 patients. Of these, 24 patients were excluded
      due to subsequent surgery. Thus, 92 patients were eligible, of whom 80 responded,
      giving an 87% response rate. The Glasgow Benefit Inventory score had a predicted
      overall mean of 13.4 (95% confidence interval: 9.9 to 17.2). Significant positive
      outcomes by multiple regression were the presence of stones (P = 0.015) and
      examination of the parotid gland (P = 0.041). CONCLUSIONS: Overall, there is a
      significant patient-perceived benefit from sialendoscopy, which is comparable to
      the benefit from tonsillectomy. The benefit is significantly higher if stones are
      found than not and for examination of the parotid gland as compared to the
      submandibular gland. LEVEL OF EVIDENCE: 4

PMID- 25988710
TI  - Pelitinib (EKB-569) targets the up-regulation of ABCB1 and ABCG2 induced by
      hyperthermia to eradicate lung cancer.
AB  - BACKGROUND AND PURPOSE: Pelitinib is a potent irreversible EGFR TK inhibitor
      currently in clinical trials for the treatment of lung cancer. Hyperthermia has
      been applied concomitantly with chemotherapy and radiotherapy to enhance
      treatment outcome. In this study, we investigated the ability of the combination
      of pelitinib with other conventional anticancer drugs to specifically target
      cancer cells with up-regulated efflux transporters ABCB1/ABCG2 after hyperthermia
      as a novel way to eradicate the cancer stem-like cells responsible for cancer
      recurrence. EXPERIMENTAL APPROACH: Alterations in intracellular topotecan
      accumulation, the efflux of fluorescent probe substrates, expression and ATPase
      activity of ABCB1/ABCG2 and tumoursphere formation capacity of side population
      (SP) cells sorted after hyperthermia were examined to elucidate the mechanism of
      pelitinib-induced chemosensitization. KEY RESULTS: While pelitinib did not
      modulate ABCB1/ABCG2 expressions, the combination of pelitinib with transporter
      substrate anticancer drugs induced more marked apoptosis, specifically in cells
      exposed to hyperthermia. The flow cytometric assay showed that both ABCB1- and
      ABCG2-mediated drug effluxes were significantly inhibited by pelitinib in a
      concentration-dependent manner. The inhibition kinetics suggested that pelitinib
      is a competitive inhibitor of ABCB1/ABCG2, which is consistent with its ability
      to stimulate their ATPase activity. SP cells sorted after hyperthermia were found
      to be more resistant to anticancer drugs, presumably due to the up-regulation of
      ABCB1 and ABCG2. Importantly, pelitinib specifically enhanced the
      chemosensitivity but reduced the tumoursphere formation capacity of these SP
      cells. CONCLUSIONS AND IMPLICATIONS: This study demonstrated a novel approach,
      exploiting drug resistance, to selectively kill cancer stem-like cells after
      hyperthermia.

PMID- 25988712
TI  - Comparative ventilatory strategies of acclimated rats and burrowing plateau pika
      (Ochotona curzoniae) in response to hypoxic-hypercapnia.
AB  - The objective of this study was to compare the different ventilatory strategies
      that help in coping with hypoxic-hypercapnia environment among two species: use
      acclimated rats and plateau pikas (Ochotona curzoniae) that live in Tibetan
      plateaus, and have been well adjusted to high altitude. Arterial blood samples
      taken at 4100 m of elevation in acclimatized rats and adapted pikas revealed
      inter-species differences with lower hemoglobin and hematocrit and higher blood
      pH in pikas. A linear and significant increase in minute ventilation was observed
      in pikas, which help them to cope with hypoxic-hypercapnia. Pikas also displayed
      a high inspiratory drive and an invariant respiratory timing regardless of the
      conditions. Biochemical analysis revealed that N-methyl-D-aspartate receptor
      (NMDA) receptor gene and nNOS gene are highly conserved between rats and pikas,
      however pikas have higher expression of NMDA receptors and nNOS compared to rats
      at the brainstem level. Taken together, these results suggest that pikas have
      developed a specific ventilatory pattern supported by a modification of the
      NMDA/NO ventilatory central pathways to survive in extreme conditions imposed on
      the Tibetan plateaus. These physiological adaptive strategies help in maintaining
      a better blood oxygenation despite high CO2 concentration in burrows at high
      altitude.

PMID- 25988714
TI  - Land use change influences soil C, N, and P stoichiometry under 'Grain-to-Green
      Program' in China.
AB  - Changes in land use might affect the combined C, N and P stoichiometry in soil.
      The Grain-to-Green Program (GTGP), which converts low-yield croplands or
      abandoned lands into forest, shrub, and/or grassland, was the largest land
      reforestation project in China. This study collected the reported C, N and P
      contents of soil in GTGP zones to achieve the factors driving the changes in the
      C:N, C:P, and N:P values. The results showed that the annual average
      precipitation exerted significant effects on the C:P value, and on the N:P value
      became significant 20 years after the change in land use. The annual average
      temperature was the main factor affecting the C:N value during the first 10
      years, while the annual average precipitation strongly affected this value
      afterwards. In addition, "Redfield-like" interactions between C, N, and P in the
      soil may exist. A linear regression revealed significant positive correlations
      between the C:N, C:P, and N:P values and the restoration age, temperature, and
      precipitation after a change in land use. Therefore large-scale changes in land
      use under the 'GTGP' program might significantly affect the C:N, C:P and N:P
      ratios in soil. 

PMID- 25988713
TI  - Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell
      of Interest Using Cell-Derived, Biomimetic Patterning.
AB  - Heterogeneity of cell populations can confound population-averaged measurements
      and obscure important findings or foster inaccurate conclusions. The ability to
      generate a homogeneous cell population, at least with respect to a chosen trait,
      could significantly aid basic biological research and development of high
      throughput assays. Accordingly, we developed a high-resolution, image-based
      patterning strategy to produce arrays of single-cell patterns derived from the
      morphology or adhesion site arrangement of user-chosen cells of interest (COIs).
      Cells cultured on both cell-derived patterns displayed a cellular architecture
      defined by their morphology, adhesive state, cytoskeletal organization, and
      nuclear properties that quantitatively recapitulated the COIs that defined the
      patterns. Furthermore, slight modifications to pattern design allowed for
      suppression of specific actin stress fibers and direct modulation of adhesion
      site dynamics. This approach to patterning provides a strategy to produce a more
      homogeneous cell population, decouple the influences of cytoskeletal structure,
      adhesion dynamics, and intracellular tension on mechanotransduction-mediated
      processes, and a platform for high-throughput cellular assays. 

PMID- 25988715
TI  - Negative impact of oxygen molecular activation on Cr(VI) removal with core-shell
      Fe@Fe2O3 nanowires.
AB  - In this study, we demonstrate that the presence of oxygen molecule can inhibit
      Cr(VI) removal with core-shell Fe@Fe2O3 nanowires at neutral pH of 6.1. 100% of
      Cr(VI) removal was achieved by the Fe@Fe2O3 nanowires within 60 min in the anoxic
      condition, in contrast, only 81.2% of Cr(VI) was sequestrated in the oxic
      condition. Removal kinetics analysis indicated that the presence of oxygen could
      inhibit the Cr(VI) removal efficiency by near 3 times. XRD, SEM, and XPS analysis
      revealed that either the anoxic or oxic Cr(VI) removal was involved with
      adsorption, reduction, co-precipitation, and re-adsorption processes. More Cr(VI)
      was bound in a reduced state of Cr(III) in the anoxic process, while a thicker
      Cr(III)/Fe(III)/Cr(VI) oxyhydroxides shell, leading to inhibiting the electron
      transfer, was found under the oxic process. The negative impact of oxygen
      molecule was attributed to the oxygen molecular activation which competed with
      Cr(VI) adsorbed for the consumption of donor electrons from Fe(0) core and
      ferrous ions bound on the iron oxides surface under the oxic condition. This
      study sheds light on the understanding of the fate and transport of Cr(VI) in
      oxic and anoxic environment, as well provides helpful guide for optimizing Cr(VI)
      removal conditions in real applications.

PMID- 25988716
TI  - Determining the selectivity of divalent metal cations for the carboxyl group of
      alginate hydrogel beads during competitive sorption.
AB  - To investigate the competitive sorption of divalent metal ions such as Ca(2+),
      Cu(2+), Ni(2+), and Pb(2+) on alginate hydrogel beads, batch and column tests
      were conducted. The concentration of carboxyl group was found to be limited in
      the preparation of spherical hydrogel beads. From kinetic test results, 80% of
      sorption was observed within 4h, and equilibrium was attained in 48 h. According
      to the comparison of the total uptake and release, divalent metal ions were found
      to stoichiometrically interact with the carboxyl group in the alginate polymer
      chain. From the Langmuir equation, the maximum capacities of Pb(2+), Cu(2+), and
      Ni(2+) were calculated to be 1.1, 0.48, and 0.13 mmol/g, respectively. The
      separation factor (alpha) values for alphaPb/Cu, alphaPb/Ni, and alphaCu/Ni were
      14.0, 98.9, and 7.1, respectively. The sorption capacity of Pb(2+) was not
      affected by the solution pH; however, the sorption capacities of Cu(2+) and
      Ni(2+) decreased with increasing solution pH, caused by competition with
      hydrogen. According to the result from the fixed column test, Pb(2+) exhibited
      the highest affinity, followed by Cu(2+) and Ni(2+), which is in exact agreement
      with those of kinetic and isotherm tests. The sorbent could be regenerated using
      4% HCl, and the regenerated sorbent exhibited 90% capacity upto 9 cycles.

PMID- 25988717
TI  - Translational regulation in chloroplasts for development and homeostasis.
AB  - Chloroplast genomes encode 100-200 proteins which function in photosynthesis, the
      organellar genetic system, and other pathways and processes. These proteins are
      synthesized by a complete translation system within the chloroplast, with
      bacterial-type ribosomes and translation factors. Here, we review translational
      regulation in chloroplasts, focusing on changes in translation rates which occur
      in response to requirements for proteins encoded by the chloroplast genome for
      development and homeostasis. In addition, we delineate the developmental and
      physiological contexts and model organisms in which translational regulation in
      chloroplasts has been studied. This article is part of a Special Issue entitled:
      Chloroplast biogenesis. 

PMID- 25988718
TI  - Contouring variability of human- and deformable-generated contours in
      radiotherapy for prostate cancer.
AB  - This study was designed to evaluate contouring variability of human-and
      deformable-generated contours on planning CT (PCT) and CBCT for ten patients with
      low-or intermediate-risk prostate cancer. For each patient in this study, five
      radiation oncologists contoured the prostate, bladder, and rectum, on one PCT
      dataset and five CBCT datasets. Consensus contours were generated using the
      STAPLE method in the CERR software package. Observer contours were compared to
      consensus contour, and contour metrics (Dice coefficient, Hausdorff distance,
      Contour Distance, Center-of-Mass [COM] Deviation) were calculated. In addition,
      the first day CBCT was registered to subsequent CBCT fractions (CBCTn: CBCT2
      CBCT5) via B-spline Deformable Image Registration (DIR). Contours were
      transferred from CBCT1 to CBCTn via the deformation field, and contour metrics
      were calculated through comparison with consensus contours generated from human
      contour set. The average contour metrics for prostate contours on PCT and CBCT
      were as follows: Dice coefficient-0.892 (PCT), 0.872 (CBCT-Human), 0.824 (CBCT
      Deformed); Hausdorff distance-4.75 mm (PCT), 5.22 mm (CBCT-Human), 5.94 mm (CBCT
      Deformed); Contour Distance (overall contour)-1.41 mm (PCT), 1.66 mm (CBCT
      Human), 2.30 mm (CBCT-Deformed); COM Deviation-2.01 mm (PCT), 2.78 mm (CBCT
      Human), 3.45 mm (CBCT-Deformed). For human contours on PCT and CBCT, the
      difference in average Dice coefficient between PCT and CBCT (approx. 2%) and
      Hausdorff distance (approx. 0.5 mm) was small compared to the variation between
      observers for each patient (standard deviation in Dice coefficient of 5% and
      Hausdorff distance of 2.0 mm). However, additional contouring variation was found
      for the deformable-generated contours (approximately 5.0% decrease in Dice
      coefficient and 0.7 mm increase in Hausdorff distance relative to human-generated
      contours on CBCT). Though deformable contours provide a reasonable starting point
      for contouring on CBCT, we conclude that contours generated with B-Spline DIR
      require physician review and editing if they are to be used in the clinic.

PMID- 25988719
TI  - Mechanisms of cell height changes that mediate epithelial invagination.
AB  - Epithelial invagination is a morphogenetic process that converts flat cell sheets
      into tubular structures and contributes to the formation of three-dimensional
      organs during development. Because the cells in tubular structures have smaller
      apical than basal surfaces, apical constriction is thought to be critical for the
      process of epithelial invagination. In addition, the invagination process is also
      accompanied by cell elongation, followed by cell shortening and basal expansion.
      While the mechanisms involved in apical constriction have been well
      characterized, recent technical advances are just beginning to unravel the
      mechanisms involved in cell height control, which include cytoskeletal changes,
      cortical tension generation, cell adhesion, and cytoplasmic flow. Furthermore,
      cell height changes associated with mitosis and apoptosis have recently been
      shown to contribute to epithelial invagination. To develop a comprehensive
      understanding of epithelial invagination, it is important to elucidate the
      mechanisms that mediate cell shape changes and facilitate their coordination. In
      this review, we summarize the recent advances in this field, focusing on the
      mechanisms that control cell height. 

PMID- 25988720
TI  - On the electrostatic nature of electrides.
AB  - The nature of electron localization in electrides is explored by examining their
      electrostatic features. Ab initio investigations of three experimentally
      synthesized and two theoretically modeled organic electrides are performed in
      order to unveil the characteristics of the trapped electron and to understand the
      reason for their low thermal stability. A single molecular unit of the electride
      extracted from the crystal structure shows an unusually deep minimum in its
      electrostatic potential, located far away from its van der Waals surface. A
      comparison of electrostatic features of the usual electron localization such as
      lone pairs has been drawn against those of the trapped electron in the crystal
      voids of electrides. Further characterization of the MESP minimum brings out the
      isotropic behavior of the trapped electrons as compared to the lone-pair minimum
      which is strongly directional. The analysis of single molecular behavior of an
      electride has been extended to the set of molecules in the unit cell of the
      crystal lattice. The present study also suggests the criteria for ligands to
      achieve thermally stable organic electrides. 

PMID- 25988721
TI  - Identification of matrix metalloproteinase inhibitors by chemical arrays.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade
      many extracellular matrix components and that have been implicated in the
      pathogenesis of various human diseases including cancer metastasis. Here, we
      screened MMP-9 inhibitors using photo-cross-linked chemical arrays, which can
      detect small-molecule ligand-protein interactions on a chip in a high-throughput
      manner. The array slides were probed sequentially with His-MMP-9, anti-His
      antibody, and a Cy5-labeled secondary antibody and then scanned with a microarray
      scanner. We obtained 27 hits among 24,275 compounds from the NPDepo library; 2 of
      the identified compounds (isoxazole compound 1 and naphthofluorescein) inhibited
      MMP-9 enzyme activity in vitro. We further explored 17 analogs of 1 and found
      that compound 18 had the strongest inhibitory activity. Compound 18 also
      inhibited other MMPs, including MMP-2, MMP-12, and MMP-13 and significantly
      inhibited cell migration in human fibrosarcoma HT1080 cells. These results
      suggest that 18 is a broad-spectrum MMP inhibitor. 

PMID- 25988722
TI  - Effect of Surface States on Terahertz Emission from the Bi2Se3 Surface.
AB  - Three-dimensional topological insulators are materials that behave as an
      insulator in the interior, but as a metal on the surface with Dirac surface
      states protected by the topological properties of the bulk wavefunctions. The
      newly discovered second surface state, located about 1.5 eV above the conduction
      band in Bi2Se3 allows direct photoexcitation of the surface electrons in n-doped
      samples with a Ti:sapphire femtosecond laser. We have observed efficient THz
      generation from the Bi2Se3 basal plane upon femtosecond optical excitation. By
      performing polarization-resolved studies on the emitted THz spectrum, two
      emission mechanisms have been identified, namely, emission generated from the
      transient photocurrent under the influence of the surface depletion field and
      from nonlinear optical rectification. The two types of emission are governed by
      distinct selection rules. And while the former is characterized by a narrow-band
      spectrum, the latter, involving almost instantaneous optical transitions, has a
      broad bandwidth and is enhanced by the presence of resonant transitions. These
      two emission mechanisms are further separated by their distinct doping dependence
      upon exposure to ambient air. With surface selectivity, THz emission spectroscopy
      thus provides a valuable spectroscopic tool for studies of the optical
      conductivity and dynamics of the surface state in centrosymmetric Bi2Se3. 

PMID- 25988723
TI  - Infantile sexuality and Freud's legacy.
AB  - The topic of sexuality and infantile sexuality, though less frequently discussed
      by psychoanalysis in recent decades, has received renewed attention for some
      years. The intention of this paper is to share some reflections around the role
      of infantile sexuality in our thinking, how we encounter it in our work with
      patients and in clinical material. Through reference to questions put forward by
      Freud (1905) in Three Essays, this paper takes into consideration some areas of
      the debate that has developed on the subject of infantile sexuality, starting
      from Freud's original intuition, including various hypotheses on the genesis of
      the sexual drive. The author will concentrate on two specific points. Firstly,
      how infantile sexuality - as a permanent dimension of the subject's existence -
      unfolds in the relationship and is deeply influenced by it. And that is how in
      childhood and adolescence, infantile sexuality ushers in parental sexuality -
      just as, in the case of our patients, infantile sexuality ushers in the analyst's
      sexuality. The second point pertains to the temporal dimension within which
      infantile sexuality is inscribed. The hypothesis that the author proposes is that
      infantile sexuality may be understood in the specific time of psychoanalysis
      [Nachtraglichkeit], distinct and different with respect to the linear,
      evolutionary dimension. 

PMID- 25988724
TI  - Magnetic resonance imaging structural alterations in brain of alcohol abusers and
      its association with impulsivity.
AB  - Despite the suggestion that impulsivity plays a central role in the transfer from
      a recreational drug use to a substance use disorder, very few studies focused on
      neurobiological markers for addiction. This study aimed to identify volumetric
      alterations in a sample of patients with mild alcohol use disorder with a short
      history of alcohol use, compared with a control group, and also focused on its
      association with impulsivity levels. Most magnetic resonance imaging studies have
      focused on severe alcohol use disorder, formerly called alcohol-dependent
      patients, showing alcohol-related structural alterations and their association
      with alcohol use history variables but not with personality parameters like
      impulsivity. Our hypothesis is that our group of alcohol users may already
      display structural alterations especially in brain regions related to inhibitory
      control like medial-prefrontal regions, and that those structural alterations
      could be more associated to personality traits like impulsivity than to drug use
      variables. Our results clearly demonstrate that our population showed lower
      regional grey and white matter volumes in the medial-prefrontal and orbitofrontal
      cortices, as well as higher regional white matter volume in the ventral striatum
      and the internal capsule. Volumetric alterations were associated to the Barratt's
      impulsivity score: the more impulsive the subjects, the lower the medial
      prefrontal cortex grey matter volume.

PMID- 25988725
TI  - Matrix metalloproteinase-sensitive size-shrinkable nanoparticles for deep tumor
      penetration and pH triggered doxorubicin release.
AB  - Nanocarriers are widely used for delivering drugs to tumors and are progressing
      in a stable trend. The enhanced permeability and retention (EPR) effect has been
      a key rationale for the development of stimulus-responsive nanocarriers to solid
      tumor. In this study, we developed a kind of novel nanocarrier, G-AuNPs-DOX-PEG,
      which was constructed with shrinkable gelatin nanoparticles coated, doxorubicin
      (DOX) tethered gold nanoparticles and long chain polyethylene glycol (PEG). The
      particle size of G-AuNPs-DOX-PEG was 186.5 nm with a zeta potential of -4.21 mV
      and the DOX loading capacity was 9.22%. In vitro, the G-AuNPs-DOX-PEG could be
      degraded by MMP-2 proteins with a size shrink from 186.5 nm to 59.3 nm. The
      release of DOX from G-AuNPs-DOX-PEG was in a pH- and time-dependent manner. At pH
      5.0, the release of DOX was much quicker than that at high pH value and the
      cumulative release rate of DOX from G-AuNPs-DOX-PEG was approach 90.9%. Cellular
      uptake demonstrated that G-AuNPs-DOX-PEG could be internalized via the endosome
      mediated pathway. Tumor spheroid penetration and collagen gel diffusion showed G
      AuNPs-DOX-PEG with pre-incubation with MMP-2 could significantly enhance its
      penetrating efficiency. In vivo and ex vivo imaging exhibit that G-AuNPs-DOX-PEG
      could distribute into 4T1 and B16F10 tumor at a highest intensity.
      Correspondingly, 4T1 and B16F10 tumor bearing mice treated with G-AuNPs-DOX-PEG
      displayed the lowest tumor growth rate. In summary, the tumor microenvironment
      sensitive size-shrinkable G-AuNPs-DOX-PEG could deliver into deep tumor region
      and then release DOX, resulting in a best anti-tumor effect. 

PMID- 25988727
TI  - Availability of extracellular matrix biopolymers and differentiation state of
      human mesenchymal stem cells determine tissue-like growth in vitro.
AB  - To explore the space-filling growth of adherent mesenchymal stem cells (MSC) into
      tissue-like structures in vitro, human bone marrow derived MSC were exposed to
      fibronectin-coated, millimeter-sized, triangular channels casted in poly(dimethyl
      siloxane) carriers. The results revealed that the three dimensional (3D) growth
      of MSC differs in dependence on differentiation status and availability of
      extracellular matrix (ECM) proteins: Massive 3D structure formation was observed
      for MSC under pro-osteogenic stimulation but not for undifferentiated MSC nor for
      MSC under pro-adipogenic stimulation; boosting cellular matrix secretion and
      addition of soluble ECM proteins caused extensive 3D tissue formation of
      undifferentiated MSC. The reported findings may contribute to bridge the gap
      between in vitro and in vivo analyses and guide the application of MSC in tissue
      replacement approaches. 

PMID- 25988726
TI  - Multifunctional envelope-type mesoporous silica nanoparticles for pH-responsive
      drug delivery and magnetic resonance imaging.
AB  - A novel multifunctional envelope-type mesoporous silica nanoparticle (MEMSN)
      system combining the merits of pH-responsiveness, non-toxicity and biological
      specificity, is demonstrated for drug delivery and magnetic resonance imaging
      (MRI). This system is constructed by immobilizing acetals on the surface of
      mesoporous silica, and then coupling to ultra small lanthanide doped upconverting
      nanoparticle, which act as a gate keeper. The anticancer drug DOX is thus locked
      in the pores, and its burst release can be achieved under acidic environment on
      account of the hydrolyzation reactions of acetals. The nanogated drug release
      system is highly efficacious for cancer therapy both in vitro and in vivo.
      Importantly, the nanocomposite could be harmlessly metabolized and degraded into
      apparently non-toxic products within a few days. The nanoscale effect of the
      system allows for passive tumor targeting and increased tumor accumulation of the
      probes via the enhanced permeation and retention (EPR) effect, which is
      visualized by MRI in vivo. Therefore, such nanosystem should be of great
      significance in the future development of highly efficient and tumor targeted
      drug delivery vehicles for cancer chemotherapy. 

PMID- 25988728
TI  - Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal
      stem cells for myocardial infarction.
AB  - Stem cell therapy has been proved to be an effective approach to ameliorate the
      heart remodeling post myocardial infarction (MI). However, poor cell engraftment
      and survival in ischemic myocardium limits the successful use of cellular therapy
      for treating MI. Here, we sought to transplant adipose derived-mesenchymal stem
      cells (AD-MSCs) with a hydrogel (NapFF-NO), naphthalene covalently conjugated a
      short peptide, FFGGG, and beta-galactose caged nitric oxide (NO) donor, which can
      release NO molecule in response to beta-galactosidase. AD-MSCs, either from
      transgenic mice that constitutively express GFP and firefly luciferase (Fluc), or
      express Fluc under the control of VEGFR2 promoter, were co-transplanted with
      NapFF-NO hydrogel into murine MI models. Improved cell survival and enhanced
      cardiac function were confirmed by bioluminescence imaging (BLI) and
      echocardiogram respectively. Moreover, increasing VEGFR2-luc expression was also
      tracked in real-time in vivo, indicating NapFF-NO hydrogel stimulated VEGF
      secretion of AD-MSCs. To investigate the therapeutic mechanism of NapFF-NO
      hydrogel, cell migration assay, paracrine action of AD-MSCs, and histology
      analysis were carried out. Our results revealed that condition medium from AD
      MSCs cultured with NapFF-NO hydrogel could promote endothelial cell migration.
      Additionally, AD-MSCs showed significant improvement secretion of angiogenic
      factors VEGF and SDF-1alpha in the presence of NapFF-NO hydrogel. Finally,
      postmortem analysis confirmed that transplanted AD-MSCs with NapFF-NO hydrogel
      could ameliorate heart function by promoting angiogenesis and attenuating
      ventricular remodeling. In conclusion, NapFF-NO hydrogel can obviously improve
      therapeutic efficacy of AD-MSCs for MI by increasing cell engraftment and
      angiogenic paracrine action. 

PMID- 25988729
TI  - Resonant light scattering from a single dielectric nano-antenna formed by
      electron beam-induced deposition.
AB  - Dielectric nano-antennas are promising elements in nanophotonics due to their low
      material loss and strong leaky-mode optical resonances. In particular, light
      scattering can be easily manipulated using dielectric nano-antennas. To take full
      advantage of dielectric nano-antennas and explore their new optical applications,
      it is necessary to fabricate three-dimensional nano-structures under arbitrary
      conditions such as in non-planar substrates. Here, we demonstrate full-visible
      range resonant light scattering from a single dielectric optical nano-rod
      antenna. The nano-rod antenna was formed by electron beam-induced deposition
      (EBID), a promising three-dimensional nanofabrication technique with a high
      spatial resolution. The nano-rods consist of amorphous alloys of C and O, with a
      width of 180 nm on average and a length of 4.5 MUm. Polarization-resolved dark
      field scattering measurements show that both transverse-electric and transverse
      magnetic mode resonances cover the full visible range as the height of the nano
      rod antenna varies from 90 to 280 nm. Numerical simulations successfully
      reproduce the measured scattering features and characterize the modal properties,
      using the critical points dispersive dielectric constant of the EBID carbonaceous
      material. Our deep understanding of resonant light scattering in the EBID
      dielectric nano-antenna will be useful for near-field measurement or for the
      implementation of three-dimensional nanophotonic devices. 

PMID- 25988730
TI  - Topical dexamethasone-cyclodextrin nanoparticle eye drops for non-infectious
      Uveitic macular oedema and vitritis - a pilot study.
AB  - PURPOSE: To evaluate the safety and efficacy of 1.5% dexamethasone nanoparticle
      (DexNP) drops in eyes with non-infectious uveitic macular oedema and vitritis.
      METHODS: In a prospective pilot study, DexNP drops were administered four times a
      day for 4 weeks followed by drops tapering over a period of another 4 weeks.
      Follow-up time was 12 weeks. RESULTS: Five eyes with macular oedema and three
      eyes with vitritis were included in the study. Best corrected visual acuity
      (BCVA) significantly improved from a median of 0.2 logMAR to a median of 0.15
      logMAR at 4 weeks' time (p < 0.05). Median BCVA was 0.175 logMAR and 0.2 logMAR,
      at week 8 and 12, respectively (p > 0.05). Macular oedema significantly improved
      at all time-points as compared to baseline (p < 0.05) and resolved in all eyes
      during follow-up. One eye had macular oedema relapse at week 12. Vitritis
      improved in all eyes and resolved completely in two eyes. One eye had intraocular
      pressure (IOP) elevation which was well controlled with topical antihypertensive
      treatment, and one eye had cataract progression. CONCLUSION: This short pilot
      study demonstrates favourable effect of 1.5% DexNP eye drops on eyes with non
      infectious uveitic macular oedema and vitritis. Further comparative long-term
      studies are warranted to assess this effect.

PMID- 25988731
TI  - Plasma-based ambient ionization mass spectrometry in bioanalytical sciences.
AB  - Plasma-based ambient ionization mass spectrometry techniques are gaining growing
      interest due to their specific features, such as the need for little or no sample
      preparation, its high analysis speed, and the ambient experimental conditions.
      Samples can be analyzed in gas, liquid, or solid forms. These techniques allow
      for a wide range of applications, like warfare agent detection, chemical reaction
      control, mass spectrometry imaging, polymer identification, and food safety
      monitoring, as well as applications in biomedical science, e.g., drug and
      pharmaceutical analysis, medical diagnostics, biochemical analysis, etc. Until
      now, the main drawback of plasma-based techniques is their quantitative aspect,
      but a lot of efforts have been done to improve this obstacle.

PMID- 25988732
TI  - Wound centers: is it time for organizational accreditation.

PMID- 25988733
TI  - Medicare changes that you may not know.

PMID- 25988734
TI  - A study of the utility and equivalency of 2 methods of wound measurement:
      digitized tracing versus digital photography.
AB  - OBJECTIVE: To examine agreement between digitized tracing and digital photography
      methods in measuring wound area and healing rate, and to compare and contrast the
      2 methods on feasibility and utility in patient care and research settings.
      SETTING: Toronto Rehabilitation Institute, University Health Network, Toronto,
      Ontario, Canada. PARTICIPANTS: A total of 20 subjects aged 18 years or older with
      a spinal cord injury and pressure ulcers that were Stage II or higher, and who
      had received in- or outpatient wound care at the hospital for at least 3
      consecutive weeks. METHODS: Wound area was measured at weekly intervals. One
      assessor calculated wound area from a digitized tracing. A second assessor
      calculated wound area using a wound photograph. Both assessors used Image-J
      software. The 2 methods were compared for differences in weekly wound area and
      weekly healing rate. RESULTS: Methods were different for wound area (P < .0001),
      whereas there was no difference between methods in weekly healing rate (P =
      .9429). CONCLUSIONS: The 2 methods are in agreement on the important parameter of
      healing rate. Both methods are feasible in clinical settings. Wound photography
      may be more useful than digitized tracings because it simultaneously captures
      wound appearance.

PMID- 25988735
TI  - A research design for the quantification of the neuropeptides substance p and
      calcitonin gene-related Peptide in rat skin using Western blot analysis.
AB  - OBJECTIVE: To describe and standardize a protocol that overcomes the technical
      limitations of Western blot (WB) analysis in the quantification of the
      neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP)
      following nociceptive stimuli in rat skin. DESIGN: Male Wistar rats (Rattus
      norvegicus albinus) weighing 250 to 350 g were used in this study. Elements of WB
      analysis were adapted by using specific manipulation of samples, repeated cycles
      of freezing and thawing, more thorough maceration, and a more potent homogenizer;
      increasing lytic reagents; promoting greater inhibition of protease activity; and
      using polyvinylidene fluoride membranes as transfer means for skin-specific
      protein. Other changes were also made to adapt the WB analysis to a rat model.
      SETTING: University research center. MAIN OUTCOME MEASURE: Western blot analysis
      adapted to a rat model. RESULTS: This research design has proven effective in
      collecting and preparing skin samples to quantify SP and CGRP using WB analysis
      in rat skin. CONCLUSION: This study described a research design that uses WB
      analysis as a reproducible, technically accessible, and cost-effective method for
      the quantification of SP and CGRP in rat skin that overcomes technical biases.

PMID- 25988736
TI  - Dressings for Preventing Pressure Ulcers: A Meta-analysis.
AB  - The purpose of this analysis is to determine the effectiveness of dressing
      material in the prevention of pressure ulcers. Results showed that hydrocolloid,
      foam, and film were more effective than a standard care protocol in patients at
      risk for pressure ulcers. 

PMID- 25988737
TI  - Practice implications for peristomal skin assessment and care from the 2014 world
      council of enterostomal therapists international ostomy guideline.
AB  - All persons with an ostomy are at risk for development of peristomal skin
      problems. This is true regardless of the person's nation of residence, type of
      stoma, or supplies available for stoma care. There are measures that can be taken
      to lessen the potential for peristomal skin problems. These measures include
      preoperative stoma site marking, preoperative education, appropriate
      pouch/barrier fitting, and pouch maintenance. The 2014 World Council of
      Enterostomal Therapists International Ostomy Guideline includes recommendations
      that can be implemented to prevent situations that may lead to peristomal skin
      complications.

PMID- 25988739
TI  - Clinical order sets for arterial ulcers.

PMID- 25988740
TI  - Neutrophil to lymphocyte ratio and risk of a first episode of stroke in patients
      with atrial fibrillation: a cohort study.
AB  - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is associated with increased
      risk of cardiovascular morbidity and mortality. We aimed to assess the
      association between NLR and first episode of stroke in patients with atrial
      fibrillation. METHODS: Using the computerized database of the largest HMO in
      Israel, we identified a cohort of adults, aged 20 years or older, with atrial
      fibrillation diagnosed before 1 January 2012. Eligible subjects had no prior
      stroke or TIA, were not on anticoagulants at baseline, and had at least one blood
      cell count performed in 2011. The cohort (32,912 subjects) was followed for the
      first event of stroke or TIA until 31 December 2012. RESULTS: Overall 981
      subjects developed stroke during a follow-up of 30,961 person-years (stroke rate,
      3.17 per 100 person-years). The incidence rate of stroke increased across NLR
      quartiles: 2.27, 2.72, 3.26 and 4.54 per 100 person-years, respectively. Cox
      proportional hazard regression analysis adjusting for the individual CHA2 DS2 
      VASc score risk factors showed that, compared with the lowest NLR quartile, the
      HR for stroke was 1.11 (95% CI, 0.91-1.35), 1.25 (1.03-1.51) and 1.56 (1.29-1.88)
      for the second, third and highest quartile, respectively. On stratified analysis,
      NLR refined the risk of stroke across all CHA2 DS2 -VASc score strata. Adding NLR
      to the CHA2 DS2 -VASc score increased the AUC from 0.627 (95% CI, 0.612-0.643) to
      0.635 (0.619-0.651) (P = 0.037). CONCLUSIONS: The neutrophil to lymphocyte ratio
      is directly associated with the risk of stroke in patients with atrial
      fibrillation. Future studies are needed to replicate these findings.

PMID- 25988741
TI  - Dealing with existential anxiety in exercise-based cardiac rehabilitation: a
      phenomenological-hermeneutic study of patients' lived experiences.
AB  - AIMS AND OBJECTIVES: To investigate patients' lived experiences of exercise-based
      cardiac rehabilitation. BACKGROUND: Exercise-based cardiac rehabilitation is used
      to enable patients with cardiac problems to move forward to lead satisfying
      lives. However, knowledge of patients' concerns while they follow the current
      programmes is sparse. DESIGN: This study, which included nine men and two women
      with unstable angina pectoris and non-ST-elevation myocardial infarction, used a
      phenomenological-hermeneutic approach. METHODS: The patients were followed by
      field observations during exercise-based cardiac rehabilitation. Focus group
      interviews were conducted at the programme end, and individual interviews were
      performed one to two months later. The interpretation comprised three
      methodological steps: naive reading, structural analysis, and comprehensive
      interpretation and discussion. FINDINGS: Although both physically and
      psychologically challenged, the patients were encouraged to maintain an active
      lifestyle. Three themes were identified: anxiety regarding exercise, whereby the
      patients are initially insecure about how to behave with their diseased hearts;
      encouragement from training together, whereby the patients support each other in
      exercising; and growing confidence in the heart, whereby the patients enjoy being
      physically active. CONCLUSIONS: In exercise-based cardiac rehabilitation,
      patients' insecurity with respect to their heart disease is revealed as an
      existential anxiety. Through peer support and a positive physical perception, the
      patients gain renewed self-efficacy, helping them to continue their lives in an
      active and satisfying way. RELEVANCE TO CLINICAL PRACTICE: Knowing that patients
      are confronted with an existential anxiety during exercise-based cardiac
      rehabilitation is important because it requires specific care. Recognising this
      anxiety also highlights how participating in the programme can be very demanding,
      which can help us understand aspects of adherence problems. Of greatest
      importance is that exercise-based cardiac rehabilitation enables patients to find
      a new foothold, which comprises enjoying being physically active.

PMID- 25988742
TI  - A metal exchange method for thiolate-protected tri-metal M(1)Ag(x)Au(24
      x)(SR)(18)(0) (M = Cd/Hg) nanoclusters.
AB  - We herein reported the first synthesis of tri-metallic M1AgxAu24-x(SR)18(0) (M =
      Cd/Hg) nanoclusters by a two-step metal exchange method. Optical spectra
      suggested that the second and third foreign metals could largely change the
      electronic structure of homogold Au25(SR)18(-) nanoclusters. This work also
      provides a novel way to find the doping site of some special metals (such as Cd),
      which can be done using silver as the isotope of gold. 

PMID- 25988743
TI  - The effects of physical exercise in children with attention deficit hyperactivity
      disorder: a systematic review and meta-analysis of randomized control trials.
AB  - OBJECTIVE: The aim of this systematic review and meta-analysis was to examine the
      evidence for the effectiveness of exercise interventions on attention deficit
      hyperactivity disorder (ADHD)-related symptoms such as inattention,
      hyperactivity/impulsivity, anxiety and cognitive functions in children and
      adolescents. METHOD: Five databases covering the period up to November 2014
      (PubMed, Scopus, EMBASE, EBSCO [E-journal, CINAHL, SportDiscus] and The Cochrane
      Library) were searched. Methodological quality was assessed using the Cochrane
      tool of bias. Standardized mean differences (SMD) and 95% confidence intervals
      were calculated, and the heterogeneity of the studies was estimated using
      Cochran's Q-statistic. RESULTS: Eight randomized controlled trials (n = 249)
      satisfied the inclusion criteria. The studies were grouped according to the
      intervention programme: aerobic and yoga exercise. The meta-analysis suggests
      that aerobic exercise had a moderate to large effect on core symptoms such as
      attention (SMD = 0.84), hyperactivity (SMD = 0.56) and impulsivity (SMD = 0.56)
      and related symptoms such as anxiety (SMD = 0.66), executive function (SMD =
      0.58) and social disorders (SMD = 0.59) in children with ADHD. Yoga exercise
      suggests an improvement in the core symptoms of ADHD. CONCLUSIONS: The main
      cumulative evidence indicates that short-term aerobic exercise, based on several
      aerobic intervention formats, seems to be effective for mitigating symptoms such
      as attention, hyperactivity, impulsivity, anxiety, executive function and social
      disorders in children with ADHD.

PMID- 25988744
TI  - Catalytic mechanism of cofactor-free dioxygenases and how they circumvent spin
      forbidden oxygenation of their substrates.
AB  - Dioxygenases catalyze a diverse range of biological reactions by incorporating
      molecular oxygen into organic substrates. Typically, they use transition metals
      or organic cofactors for catalysis. Bacterial 1-H-3-hydroxy-4-oxoquinaldine-2,4
      dioxygenase (HOD) catalyzes the spin-forbidden transfer of dioxygen to its N
      heteroaromatic substrate in the absence of any cofactor. We combined kinetics,
      spectroscopic and computational approaches to establish a novel reaction
      mechanism. The present work gives insight into the rate limiting steps in the
      reaction mechanism, the effect of first-coordination sphere amino acids as well
      as electron-donating/electron-withdrawing substituents on the substrate. We
      highlight the role of active site residues Ser101/Trp160/His251 and their
      involvement in the reaction mechanism. The work shows, for the first time, that
      the reaction is initiated by triplet dioxygen and its binding to deprotonated
      substrate and only thereafter a spin state crossing to the singlet spin state
      occurs. As revealed by steady- and transient-state kinetics the oxygen-dependent
      steps are rate-limiting, whereas Trp160 and His251 are essential residues for
      catalysis and contribute to substrate positioning and activation, respectively.
      Computational modeling further confirms the experimental observations and
      rationalizes the electron transfer pathways, and the effect of substrate and
      substrate binding pocket residues. Finally, we make a direct comparison with iron
      based dioxygenases and explain the mechanistic and electronic differences with
      cofactor-free dioxygenases. Our multidisciplinary study confirms that the
      oxygenation reaction can take place in absence of any cofactor by a unique
      mechanism in which the specially designed fit-for-purpose active-site
      architecture modulates substrate reactivity toward oxygen. 

PMID- 25988745
TI  - Surgical Success in Chronic Pancreatitis: Sequential Endoscopic Retrograde
      Cholangiopancreatography and Surgical Longitudinal Pancreatojejunostomy (Puestow
      Procedure).
AB  - Introduction Chronic pancreatitis (CP) can be a cause of recurrent, severe,
      disabling abdominal pain in children. Surgery has been suggested as a useful
      therapy, although experience is limited and the results unpredictable. We
      reviewed our experience of a two-stage protocol-preliminary endoscopic retrograde
      cholangiopancreatography (ERCP) and duct stenting, and if symptoms resolved,
      definitive surgical decompression by longitudinal pancreatojejunostomy (LPJ)
      (Puestow operation). Patients and Methods This is a single-center, retrospective
      review of children with established CP who underwent an LPJ between February 2002
      and September 2012. A questionnaire was completed (incorporating visual analog
      scale pain and lifestyle scores) to assess functional outcome. Data are expressed
      as median (range). Results In this study, eight (M:F ratio of 4:4) children
      underwent an LPJ and one female child had a more limited pancreatojejunostomy
      anastomosis following preliminary ERCP and stent placement where possible.
      Diagnoses included hereditary pancreatitis (n = 3), idiopathic or structural
      pancreatitis (n = 5), and duct stricture following radiotherapy (n = 1). Median
      duct diameter presurgery was 5 (4-11) mm. Endoscopic placement of a Zimmon
      pancreatic stent was possible in six with relief of symptoms in all. Median age
      at definitive surgery was 11 (range, 7-17) years with a median postoperative stay
      of 9 (range, 7-12) days and a follow-up of 6 (range, 0.5-12) years. All children
      reported markedly reduced episodes of pain postprocedure. One developed diabetes
      mellitus, while three had exocrine deficiency (fecal elastase < 200 ug/g)
      requiring enzyme supplementation. The child with limited LPJ had symptomatic
      recurrence and required restenting and further surgery to widen the anastomosis
      to become pain free. Conclusion ERCP and stenting provide a therapeutic trial to
      assess possible benefit of a definitive duct drainage procedure. LPJ-the modified
      Puestow operation was safe and complication-free with good medium-term relief of
      symptoms. We were not able to identify a consistent etiology-associated outcome. 

PMID- 25988746
TI  - Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Differentiated from
      Biliary Atresia.
AB  - Purpose The aim of this article is to differentiate neonatal intrahepatic
      cholestasis caused by citrin deficiency (NICCD) from biliary atresia (BA) by
      total hexose. Methods A total of 11 patients with NICCD, 29 patients with BA, and
      4,898 children as controls were involved in this study. The blood concentration
      of amino acids, carnitine, acylcarnitines, and total hexose were measured in dry
      blood spots (DBS) using tandem mass spectrometry (MS/MS). Results In the patients
      with NICCD, the blood concentration of the total hexose (15.3 +/- 9.0 mmol/L vs.
      7.3 +/- 2.7 mmol/L; p < 0.001), citrulline (Cit) (197.9 +/- 93.7 umol/L vs. 17.5
      +/- 7.4 umol/L; p < 0.001) were higher than those of patients with BA. Using
      total hexose (> 10 mmol/L), Cit (> 55 umol/L) to diagnose NICCD, the sensitivity
      and specificity were 66.7 and 97.8% and 90.0 and 99.1%, respectively, and all of
      the areas under the receiver-operating characteristic curves were greater than
      0.85. Conclusion Elevated total hexose in DBS measured by MS/MS associated with
      elevated amino acids, especially Cit can be used to diagnose NICCD and
      differentiate it from BA. 

PMID- 25988747
TI  - Vesicoscopic Treatment of Symptomatic Congenital Bladder Diverticula in Children:
      A 7-Year Experience.
AB  - Introduction The objective of this study was to report on the use of vesicoscopy
      in the treatment of symptomatic congenital bladder diverticula (CBD) in children.
      Material and Methods In this study, 16 males, aged 4 to 12 years (median age,
      6.25 years), were treated for symptomatic CBD; 3 patients presented double
      diverticulum and 13 presented single diverticulum. The presenting symptoms were
      recurrent urinary tract infection, hematuria, lower abdominal pain, and voiding
      dysfunctions as urgency, frequency alone, or in association. A first midline 5-mm
      trocar was introduced for a 0-degree telescope at the dome of the bladder, and
      two left and right 3- or 5-mm trocars were inserted through the anterolateral
      wall. The bladder was then insufflated with carbon dioxide to 10 to 12 mm Hg
      pressure. The diverticula were inverted into the bladder and the mucosa around
      the neck was circumcised by using scissors and hook. The defect was sutured and
      the bladder was drained. Vesicoureteral reflux (VUR) of third grade or higher was
      treated endoscopically. Results Mean operative time was 90 minutes for
      procedures. At 6-month follow-up, ultrasound and voiding cystourethrogram (VCUG)
      showed the disappearance of the diverticulum in 15 out of the 16 patients. The
      patient, with huge double diverticulum and fourth grade right VUR, presented
      recurrence of a small left diverticulum. Patients with voiding disorders
      presented a gradual improvement of their urgency. VUR disappeared at VCUG in all
      patients. Conclusion Vesicoscopic diverticulectomy resulted a safe and effective
      procedure and can be considered a valid alternative to the open or laparoscopic
      procedures. In our opinion, routine use of vesicoscopy could become the gold
      standard for the treatment of CBD in children. 

PMID- 25988748
TI  - Endoscopic Surveillance for Congenital Diaphragmatic Hernia: Unexpected
      Prevalence of Silent Esophagitis.
AB  - Introduction Gastroesophageal reflux disease (GERD) is a frequent comorbidity
      after congenital diaphragmatic hernia (CDH) repair. Our aim was to evaluate the
      clinical and endoscopic prevalence of esophagitis in a long-term follow-up of CDH
      patients. Materials and Methods Patients operated on for posterolateral CDH and
      undergoing general anesthesia for concomitant pathologies between January and
      October 2013 were included in the study. GERD was investigated both clinically
      (Manterola questionnaire) and endoscopically. The severity of esophagitis was
      evaluated according to the Hetzel-Dent classification and multiple biopsies were
      performed. The correlation between clinical score and severity of esophagitis was
      evaluated. Results Twelve patients were included in the study (mean age: 14.5
      years; range, 9-18 years). Only three children (25%) had a pathological
      questionnaire. At endoscopy, three children (25%) were affected by grade 1
      esophagitis, six (50%) by grade 2, two (17%) by grade 3, and one (8%) by grade 4.
      One of the children presented Barrett esophagus. A moderate negative correlation
      was found between clinical data and endoscopic findings (r: -0.54 and p: 0.067).
      Conclusion Even in the absence of symptoms, esophagitis revealed to have a high
      prevalence in CDH patients. A long-term clinical and instrumental follow-up is
      mandatory to early diagnose and treat GERD. 

PMID- 25988749
TI  - Failure of First-Line Antibiotics in Nonoperative Management of Appendiceal Mass,
      toward a Second-Line Instead of Surgery?
AB  - Background Conservative approach for complicated appendicitis has been gradually
      adopted in children to decrease postoperative morbidity. The first aim of this
      study was to assess the efficacy of a second-line antibiotics enlarged on
      Pseudomonas aeruginosa and Enterococcus in case of poor clinical outcome after
      initial conservative approach for appendiceal mass and abscess. The second aim of
      this study was to identify predictive factors of failure of first-line
      antibiotics. Methods We performed a prospective review of all the cases of
      appendiceal mass or abscess managed at our institution between November 2007 and
      September 2011 after implementation of a conservative protocol including a second
      line antibiotics in case of poor initial clinical outcome. Results A total of 64
      consecutive patients were included. We observed a success in 46 patients after
      the first-line antibiotics and in 14 of the remaining patients after the second
      line. The only predictive factor of failure of the first-line antibiotics was a
      shorter duration of symptoms before admission (p = 0.02). Laparoscopic
      appendectomy was performed in all the cases (emergency or interval procedure)
      with six postoperative complications and two conversions to open surgery.
      Conclusions A gradual adapted antibiotherapy in nonoperative management of
      appendiceal abscess and mass is effective. We found no relevant predictive factor
      of failure of the first-line antibiotics. 

PMID- 25988750
TI  - Does Severity of Pelvic Fractures Correlate with the Incidence of Associated
      Intra-Abdominal Injuries in Children?
AB  - Background Pelvic fractures are considered a marker of injury severity,
      especially in the pediatric population. However, the correlation between the
      severity of pelvic fractures and incidence of associated abdominal injuries is
      not clear. Methods A retrospective cohort study involving blunt trauma patients
      up to the age of 14 years, who suffered from pelvic fractures, with or without
      associated intra-abdominal injuries. Results A total of 812 trauma patients were
      included in this study. Overall, 671 of them suffered from pelvic fractures with
      abbreviated injury scale (AIS) of 2, 103 with AIS of 3, and 38 with AIS of 4 to
      5. Overall mortality was found to be 5.2%, strongly correlating with the severity
      of the pelvic fractures (p value < 0.0001). There was no correlation between the
      incidence of most extrapelvic abdominal organ injuries (liver, spleen, small
      bowel, and pancreas) and the severity of pelvic fractures. A significant
      correlation was found with intrapelvic organ injuries (p value < 0.0001) and
      kidney injuries (p = 0.03). Conclusions Mortality of pediatric trauma patients
      with pelvic fractures is correlated with the severity of the fractures. An
      increase in the severity of pelvic fractures in this population is associated
      with an increased incidence of pelvic organ injury, but is not associated with
      the presence of extrapelvic abdominal injuries, except for kidney injuries. 

PMID- 25988752
TI  - There and back again: revisiting the on-time effect.
AB  - In apparent motion, static stimuli presented successively in shifted locations
      produce a subjective percept of continuous motion. Reducing stimulus exposure (or
      on-time) was shown to consistently increase the perceived velocity of apparent
      motion (Vision Research 29 (1989), 335-347), yet surprisingly little
      investigation has followed up on the discovery of this illusion. In five
      experiments, we delineate the boundary conditions of the on-time illusion in
      order to clarify its underlying mechanisms. Subjects viewed multi-item apparent
      motion displays, in which at some point, on-time duration either increased or
      decreased. Objective velocity remained unchanged, yet participants had to judge
      whether they perceived the motion to become slower or faster. We observed the on
      time illusion during both fast and slow apparent motion. The effect was not
      modulated by stimulus luminance, thus precluding an energy-summation account of
      the illusion. It generalized from speed perception to time perception in a
      temporal bisection task. The illusion was specific to apparent motion, as it did
      not occur with veridical motion. Finally, the illusion persisted when on-time and
      off-time were not confounded, that is, when off-time remained constant. These
      findings are discussed in the framework of current models of motion perception.

PMID- 25988751
TI  - Large-scale recent expansion of European patrilineages shown by population
      resequencing.
AB  - The proportion of Europeans descending from Neolithic farmers ~ 10 thousand years
      ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male
      specific region of the Y chromosome (MSY) has been widely applied to this
      question, but unbiased estimates of diversity and time depth have been lacking.
      Here we show that European patrilineages underwent a recent continent-wide
      expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European
      and Middle Eastern populations, defines a phylogeny containing 5,996 single
      nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and
      R1b), accounting for 64% of our sample, have very recent coalescent times,
      ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share
      similar histories featuring a demographic expansion starting ~ 2.1-4.2 KYA. Our
      results are compatible with ancient MSY DNA data, and contrast with data on
      mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses
      interest on the social structure of Bronze Age Europe.

PMID- 25988753
TI  - Visual search under scotopic lighting conditions.
AB  - When we search for visual targets in a cluttered background we systematically
      move our eyes around to bring different regions of the scene into foveal view. We
      explored how visual search behavior changes when the fovea is not functional, as
      is the case in scotopic vision. Scotopic contrast sensitivity is significantly
      lower overall, with a functional scotoma in the fovea. We found that in scotopic
      search, for a medium- and a low-spatial-frequency target, individuals made longer
      lasting fixations that were not broadly distributed across the entire search
      display but tended to peak in the upper center, especially for the medium
      frequency target. The distributions of fixation locations are qualitatively
      similar to those of an ideal searcher that has human scotopic detectability
      across the visual field, and interestingly, these predicted distributions are
      different from those predicted by an ideal searcher with human photopic
      detectability. We conclude that although there are some qualitative differences
      between human and ideal search behavior, humans make principled adjustments in
      their search behavior as ambient light level decreases. 

PMID- 25988754
TI  - Prenatal diagnosis of fragile X syndrome complicated by full mutation retraction.

PMID- 25988756
TI  - Schedule-induced polydipsia is associated with increased spine density in
      dorsolateral striatum neurons.
AB  - Schedule-induced polydipsia (SIP) is an adjunctive behavior in which rats exhibit
      excessive drinking as a consequence of intermittent feeding, and it has been
      proposed as a candidate model to study the development of compulsive and
      repetitive behavior. Although several brain structures are involved in compulsive
      behavior, it has been suggested that alterations in fronto-striatal circuits may
      underlie compulsive spectrum disorders. In the present work, we examined whether
      SIP would induce modifications in dorsolateral striatum (DLS) and anterior
      prefrontal cortex (aPFC) neurons. Specifically, the effects of 20 sessions of SIP
      were determined in the dendrites of DLS medium spiny neurons and in the basal
      dendritic arbors of layer V pyramidal cells in the aPFC. The structure, size and
      branching complexity in aPFC neurons were also studied. Results showed that SIP
      resulted in an increase in dendritic spine density in DLS neurons. Moreover,
      dendritic spine density was highly correlated with the level of drinking in
      animals subjected to SIP. By contrast, we observed no differences either in
      dendritic spine density or in the morphological structure of the dendrites of the
      aPFC in SIP rats compared to their control counterparts. We hypothesize that SIP
      induced structural plasticity in DLS neurons could be related to inflexible
      response in compulsive behavior. The findings of this study could provide new
      insights into the involvement of particular cell populations of the dorsolateral
      striatum and anterior prefrontal cortex regions in compulsive spectrum disorders.

PMID- 25988755
TI  - Secretory autophagy.
AB  - Autophagy, once viewed exclusively as a cytoplasmic auto-digestive process, has
      its less intuitive but biologically distinct non-degradative roles. One
      manifestation of these functions of the autophagic machinery is the process
      termed secretory autophagy. Secretory autophagy facilitates unconventional
      secretion of the cytosolic cargo such as leaderless cytosolic proteins, which
      unlike proteins endowed with the leader (N-terminal signal) peptides cannot enter
      the conventional secretory pathway normally operating via the endoplasmic
      reticulum and the Golgi apparatus. Secretory autophagy may also export more
      complex cytoplasmic cargo and help excrete particulate substrates. Autophagic
      machinery and autophagy as a process also affect conventional secretory pathways,
      including the constitutive and regulated secretion, as well as promote
      alternative routes for trafficking of integral membrane proteins to the plasma
      membrane. Thus, autophagy and autophagic factors are intimately intertwined at
      many levels with secretion and polarized sorting in eukaryotic cells. 

PMID- 25988757
TI  - Inflammation in nervous system disorders. Introduction.

PMID- 25988758
TI  - One-pot hydrogen peroxide and hydrohalic acid induced ring closure and selective
      aromatic halogenation to give new ring-fused benzimidazoles.
AB  - A new series of selectively dichlorinated and dibrominated five- to eight
      membered-ring [1,2-a]-fused benzimidazoles and [1,4]oxazino[4,3-a]benzimidazoles
      are synthesized in mostly high yields of >80% using the reaction of hydrogen
      peroxide and hydrohalic acid with commercially available o-cyclic amine
      substituted anilines. Domestic bleach with HCl can also be used for a one-pot
      ring closure and chlorination. 

PMID- 25988759
TI  - Low haemoglobin concentration in Tibetan males is associated with greater high
      altitude exercise capacity.
AB  - Tibetans living at high altitude have adapted genetically such that many display
      a low erythropoietic response, resulting in near sea-level haemoglobin (Hb)
      concentration. We hypothesized that absence of the erythropoietic response would
      be associated with greater exercise capacity compared to those with high [Hb] as
      a result of beneficial changes in oxygen transport. We measured, in 21 Tibetan
      males with [Hb] ranging from 15.2 g dl(-1) to 22.9 g dl(-1) (9.4 mmol l(-1) to
      14.2 mmol l(-1) ), [Hb], ventilation, volumes of O2 and CO2 utilized at peak
      exercise (VO2 and VCO2), heart rate, cardiac output and arterial blood gas
      variables at peak exercise on a cycle ergometer at ~4200 m. Lung and muscle O2
      diffusional conductances were computed from these measurements. [Hb] was related
      (negatively) to VO2 kg(-1) (r = -0.45, P< 0.05), cardiac output kg(-1) (QT kg(-1)
      , r = -0.54, P < 0.02), and O2 diffusion capacity in muscle (DM kg(-1) , r = 
      0.44, P<0.05), but was unrelated to ventilation, arterial partial pressure of O2
      (PaO2) or pulmonary diffusing capacity. Using multiple linear regression,
      variance in peak VO2 kg(-1) was primarily attributed to QT, DM, and PCO2 (R(2) =
      0.88). However, variance in pulmonary gas exchange played essentially no role in
      determining peak VO2. These results (1) show higher exercise capacity in Tibetans
      without the erythropoietic response, supported mostly by cardiac and muscle O2
      transport capacity and ventilation rather than pulmonary adaptations, and (2)
      support the emerging hypothesis that the polycythaemia of altitude, normally a
      beneficial response to low cellular PO2, may become maladaptive if excessively
      elevated under chronic hypoxia. The cause and effect relationships among [Hb],
      QT, DM, and PCO2 remain to be elucidated.

PMID- 25988761
TI  - Nutritional adequacy of dietary intake in women with anorexia nervosa.
AB  - Understanding nutrient intake of anorexia nervosa (AN) patients is essential for
      the treatment. Therefore, estimates of total energy and nutrient consumption were
      made in a group of young women (19 to 30 years) with restricting and binge purge
      subtypes of AN participating in an ecological momentary assessment study.
      Participants completed three nonconsecutive 24-hour diet recalls. Mean nutrient
      intakes were stratified by subtype and by quartiles of energy intake and compared
      to the age specific Dietary Reference Intake (DRI) levels, as well as to the
      reported intakes from the What We Eat In America (WWEIA) dietary survey 2011
      2012. Reported intake was determined for energy, macronutrients, and
      micronutrients. The mean body mass index (BMI) for all participants was 17.2 +/-
      0.1 kg/m2. Reported nutrient intake was insufficient for participants in
      quartiles 1-3 of both AN subtypes when compared to the DRIs. Intake reported by
      participants in quartile 4 of both subgroups met requirements for most nutrients
      and even met or exceeded estimated energy needs. Counseling of AN patients should
      be directed to total food consumption to improve energy intake and to reduce
      individual nutritional gaps. 

PMID- 25988762
TI  - No positive influence of ingesting chia seed oil on human running performance.
AB  - Runners (n = 24) reported to the laboratory in an overnight fasted state at 8:00
      am on two occasions separated by at least two weeks. After providing a blood
      sample at 8:00 am, subjects ingested 0.5 liters flavored water alone or 0.5
      liters water with 7 kcal kg-1 chia seed oil (random order), provided another
      blood sample at 8:30 am, and then started running to exhaustion (~70% VO2max).
      Additional blood samples were collected immediately post- and 1-h post-exercise.
      Despite elevations in plasma alpha-linolenic acid (ALA) during the chia seed oil
      (337%) versus water trial (35%) (70.8 +/- 8.6, 20.3 +/- 1.8 MUg mL(-1),
      respectively, p < 0.001), run time to exhaustion did not differ between trials
      (1.86 +/- 0.10, 1.91 +/- 0.13 h, p = 0.577, respectively). No trial differences
      were found for respiratory exchange ratio (RER) (0.92 +/- 0.01), oxygen
      consumption, ventilation, ratings of perceived exertion (RPE), and plasma glucose
      and blood lactate. Significant post-run increases were measured for total
      leukocyte counts, plasma cortisol, and plasma cytokines (Interleukin-6 (IL-6),
      Interleukin-8 (IL-8), Interleukin-10 (IL-10), and Tumor necrosis factors-alpha
      (TNF-alpha)), with no trial differences. Chia seed oil supplementation compared
      to water alone in overnight fasted runners before and during prolonged, intensive
      running caused an elevation in plasma ALA, but did not enhance run time to
      exhaustion, alter RER, or counter elevations in cortisol and inflammatory outcome
      measures.

PMID- 25988760
TI  - Selenium and chronic diseases: a nutritional genomics perspective.
AB  - Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in
      biological pathways known to be altered in multifactorial diseases, such as
      cellular maintenance, response to oxidative stress and correct protein folding.
      Although epidemiological studies indicate that low Se intake is linked to
      increased risk for various chronic diseases, supplementation trials have given
      confusing outcomes, suggesting that additional genetic factors could affect the
      relationship between Se and health. Genetic data support this hypothesis, as risk
      for several chronic diseases, in particular cancer, was linked to a number of
      single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein
      synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in
      related molecular pathways and biomarkers of Se status were found to further
      modulate the genetic risk carried by the SNPs. Taken together, nutritional
      genomics approaches uncovered the potential implication of some selenoproteins as
      well as the influence of complex interactions between genetic variants and Se
      status in the aetiology of several chronic diseases. This review discusses the
      results from these genetic associations in the context of selenoprotein functions
      and epidemiological investigations and emphasises the need to assess in future
      studies the combined contribution of Se status, environmental stress, and
      multiple or individual SNPs to disease risk. 

PMID- 25988763
TI  - Predictors of Energy Compensation during Exercise Interventions: A Systematic
      Review.
AB  - Weight loss from exercise-induced energy deficits is usually less than expected.
      The objective of this systematic review was to investigate predictors of energy
      compensation, which is defined as body energy changes (fat mass and fat-free
      mass) over the total amount of exercise energy expenditure. A search was
      conducted in multiple databases without date limits. Of 4745 studies found, 61
      were included in this systematic review with a total of 928 subjects. The overall
      mean energy compensation was 18% +/- 93%. The analyses indicated that 48% of the
      variance of energy compensation is explained by the interaction between initial
      fat mass, age and duration of exercise interventions. Sex, frequency, intensity
      and dose of exercise energy expenditure were not significant predictors of energy
      compensation. The fitted model suggested that for a shorter study duration, lower
      energy compensation was observed in younger individuals with higher initial fat
      mass (FM). In contrast, higher energy compensation was noted for younger
      individuals with lower initial FM. From 25 weeks onward, energy compensation was
      no longer different for these predictors. For studies of longer duration (about
      80 weeks), the energy compensation approached 84%. Lower energy compensation
      occurs with short-term exercise, and a much higher level of energy compensation
      accompanies long-term exercise interventions. 

PMID- 25988764
TI  - Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size
      Distribution and Oxidation.
AB  - Sex differences have been previously highlighted in the cardioprotective effects
      of the Mediterranean diet (MedDiet). The objective of this study was to
      investigate whether sex differences also exist with regard to LDL particle size
      distribution and oxidation. Participants were 37 men and 32 premenopausal women
      (24-53 years) with slightly elevated LDL-C concentrations (3.4-4.9 mmol/L) or
      total cholesterol/HDL-C >=5.0. Variables were measured before and after a four
      week isoenergetic MedDiet. Sex differences were found in response to the MedDiet
      for the proportion of medium LDL (255-260 A) (p for sex-by-time interaction =
      0.01) and small, dense LDL (sdLDL; <255 A) (trend; p for sex-by-time interaction
      = 0.06), men experiencing an increase in the proportion of medium LDL with a
      concomitant reduction in the proportion of sdLDL, while an opposite trend was
      observed in women. A sex difference was also noted for estimated cholesterol
      concentrations among sdLDL (p for sex-by-time interaction = 0.03), with only men
      experiencing a reduction in response to the MedDiet. The MedDiet marginally
      reduced oxidized LDL (oxLDL) concentrations (p = 0.07), with no sex difference.
      Results suggest that short-term consumption of the MedDiet leads to a favorable
      redistribution of LDL subclasses from smaller to larger LDL only in men. These
      results highlight the importance of considering sex issues in cardiovascular
      benefits of the MedDiet. 

PMID- 25988765
TI  - Evaluation of drinks contribution to energy intake in summer and winter.
AB  - All drinks hydrate and most also provide nutrients and energy. Our objective was
      to evaluate the contribution of drinks to total energy intake in summer and
      winter. Data were obtained using the Water Balance Questionnaire (WBQ) from a
      sample of the general population in Athens, Greece (n = 984), 473 individuals (42
      +/- 18 years) in summer and 511 individuals (38 +/- 20 years) in winter
      stratified by sex and age. The WBQ embeds a semi-quantitative food frequency
      questionnaire of 58 foods and the Short International Physical Activity
      Questionnaire. Data were analyzed for the contribution of drinks to total energy
      intake. In winter, total energy intake was 2082 +/- 892 kcal/day; energy intake
      from drinks was 479 +/- 286 kcal/day and energy expenditure 1860 +/- 390
      kcal/day. In summer, total energy intake was 1890 +/- 894 kcal/day, energy intake
      from drinks 492 +/- 499 kcal/day and energy expenditure 1830 +/- 491 kcal/day.
      Energy intake from drinks in summer was higher than in winter (p < 0.001) and in
      men higher than in women in both seasons (p < 0.001 in summer, p = 0.02 in
      winter). Coffee, coffee drinks, milk, chocolate milk and alcoholic drinks
      contributed approximately 75% of energy from drinks. Fruit juice and sugar
      sweetened drinks, including soft drinks and fruit juice based drinks, were
      consumed less frequently contributing up to 25% of drink energy intake. Drinks
      contribute approximately 1/4 of total energy intake depending on the energy
      content of the drink and frequency of consumption. Coffee, dairy and alcoholic
      drinks were the main energy contributors. 

PMID- 25988766
TI  - Carbohydrate electrolyte solutions enhance endurance capacity in active females.
AB  - The purpose of the present study was to investigate the effects of
      supplementation with a carbohydrate-electrolyte solution (CES) in active females
      during a prolonged session of submaximal running to exhaustion. Eight healthy
      active females volunteered to perform a session of open-ended running to
      exhaustion at 70% of their maximal oxygen consumption on a treadmill during the
      follicular phase of their menstrual cycle on two occasions. During each run, the
      subjects consumed either 3mL.kg(-1) body mass of a 6% CES or a placebo drink (PL)
      every 20 min during exercise. The trials were administered in a randomized double
      blind, cross-over design. During the run, the subjects ingested similar volumes
      of fluid in two trials (CES: 644 +/- 75 mL vs. PL: 593 +/- 66 mL, p > 0.05). The
      time to exhaustion was 16% longer during the CES trial (106.2 +/- 9.4 min) than
      during the PL trial (91.6 +/- 5.9 min) (p < 0.05). At 45 min during exercise, the
      plasma glucose concentration in the CES trial was higher than that in PL trial.
      No differences were observed in the plasma lactate level, respiratory exchange
      ratio, heart rate, perceived rate of exertion, sensation of thirst, or abdominal
      discomfort between the two trials (p > 0.05). The results of the present study
      confirm that CES supplementation improves the moderate intensity endurance
      capacity of active females during the follicular phases of the menstrual cycle.
      However, the exogenous oxidation of carbohydrate does not seem to explain the
      improved capacity after CES supplementation.

PMID- 25988767
TI  - Impact of leucine supplementation on exercise training induced anti-cardiac
      remodeling effect in heart failure mice.
AB  - Leucine supplementation potentiates the effects of aerobic exercise training
      (AET) on skeletal muscle; however, its potential effects associated with AET on
      cardiac muscle have not been clarified yet. We tested whether leucine
      supplementation would potentiate the anti-cardiac remodeling effect of AET in a
      genetic model of sympathetic hyperactivity-induced heart failure in mice
      (alpha2A/alpha2CARKO). Mice were assigned to five groups: wild type mice treated
      with placebo and sedentary (WT, n = 11), alpha2A/alpha2CARKO treated with placebo
      and sedentary (KO, n = 9), alpha2A/alpha2CARKO treated with leucine and sedentary
      (KOL, n = 11), alpha2A/alpha2CARKO treated with placebo and AET (KOT, n = 12) or
      alpha2A/alpha2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of
      four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal
      speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo
      (distilled water). The AET significantly improved exercise capacity, fractional
      shortening and re-established cardiomyocytes' diameter and collagen fraction in
      KOT. Additionally, AET significantly prevented the proteasome hyperactivity,
      increased misfolded proteins and HSP27 expression. Isolated leucine
      supplementation displayed no effect on cardiac function and structure (KOL),
      however, when associated with AET (KOLT), it increased exercise tolerance to a
      higher degree than isolated AET (KOT) despite no additional effects on AET
      induced anti-cardiac remodeling. Our results provide evidence for the modest
      impact of leucine supplementation on cardiac structure and function in exercised
      heart failure mice. Leucine supplementation potentiated AET effects on exercise
      tolerance, which might be related to its recognized impact on skeletal muscle. 

PMID- 25988768
TI  - Hypolipidemic effects and safety of Lactobacillus reuteri 263 in a hamster model
      of hyperlipidemia.
AB  - We aimed to verify the beneficial effects of probiotic strain Lactobacillus
      reuteri 263 (Lr263) on hypolipidemic action in hamsters with hyperlipidemia
      induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet
      (HCD)). Male Golden Syrian hamsters were randomly divided into two groups: normal
      (n = 8), standard diet (control), and experimental (n = 32), a HCD. After a two
      week induction followed by a six-week supplementation with Lr263, the 32
      hyperlipidemic hamsters were divided into four groups (n = 8 per group) to
      receive vehicle or Lr263 by oral gavage at 2.1, 4.2, or 10.5 * 10(9) cells/kg/day
      for 6 weeks, designated the HCD, 1X, 2X and 5X groups, respectively. The efficacy
      and safety of Lr263 supplementation were evaluated by lipid profiles of serum,
      liver and feces and by clinical biochemistry and histopathology. HCD
      significantly increased serum levels of total cholesterol (TC), triacylglycerol
      (TG) cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density
      lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG
      levels, and degree of fatty liver as compared with controls. Lr263
      supplementation dose dependently increased serum HDL-C level and decreased serum
      TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG
      level. In addition, Lr263 supplementation had few subchronic toxic effects. Lr263
      could be a potential agent with a hypolipidemic pharmacological effect.

PMID- 25988770
TI  - Correction to Synthesis of a Smoothened Cholesterol: 18,19-Di-nor-cholesterol.

PMID- 25988769
TI  - Oral zinc supplementation reduces the erythropoietin responsiveness index in
      patients on hemodialysis.
AB  - BACKGROUND: In hemodialysis (HD) patients, zinc depletion caused by inadequate
      intake, malabsorption, and removal by HD treatment leads to erythropoiesis
      stimulating agent (ESA) hyporesponsiveness. This study investigated the effects
      of zinc supplementation in HD patients with zinc deficiency on changes in the
      erythropoietin responsiveness index (ERI). METHODS: Patients on HD with low serum
      zinc levels (<65 MUg/dL) were randomly assigned to two groups: The polaprezinc
      group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and
      the control group (no supplementation) (n = 35) for 12 months. All the 70
      patients had been taking epoetin alpha as treatment for renal anemia. ERI was
      measured with the following equation: Weekly ESA dose (units)/dry weight
      (kg)/hemoglobin (g/dL). RESULTS: There were no significant changes in hemoglobin
      levels within groups or between the control and polaprezinc groups during the
      study period. Although reticulocyte counts were increased immediately after zinc
      supplementation, this change was transient. Serum zinc levels were significantly
      increased and serum copper levels were significantly decreased in the polaprezinc
      group after three months; this persisted throughout the study period. Although
      there was no significant change in the serum iron or transferrin saturation
      levels in the polaprezinc group during the study period, serum ferritin levels
      significantly decreased following polaprezinc treatment. Further, in the
      polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months
      and nine months, respectively, as compared with the baseline value. Multiple
      stepwise regression analysis revealed that the change in the serum zinc level was
      an independent predictor of lowered ERI. CONCLUSIONS: Zinc supplementation
      reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for
      patients with renal anemia and low serum zinc levels.

PMID- 25988771
TI  - Analysis of multi-source metabolomic data using joint and individual variation
      explained (JIVE).
AB  - Metabolic profiling is increasingly being used for understanding biological
      processes but there is no single analytical technique that provides a complete
      quantitative or qualitative profiling of the metabolome. Data fusion (i.e. joint
      analysis of data from multiple sources) has the potential to circumvent this
      issue facilitating knowledge discovery and reliable biomarker identification.
      Another field of application of data fusion is the simultaneous analysis of
      metabolomic changes through several biofluids or tissues. However, metabolomics
      typically deals with large datasets, with hundreds to thousands of variables and
      the identification of shared and individual factors or structures across multiple
      sources is challenging due to the high variable to sample ratios and differences
      in intensity and noise range. In this work we apply a recent method, Joint and
      Individual Variation Explained (JIVE), for the integrated unsupervised analysis
      of metabolomic profiles from multiple data sources. This method separates the
      shared patterns among data sources (i.e. the joint structure) from the individual
      structure of each data source that is unrelated to the joint structure. Two
      examples are described to show the applicability of JIVE for the simultaneous
      analysis of multi-source data using: (i) plasma samples subjected to different
      analytical techniques, sample treatment and measurement conditions; and (ii)
      plasma and urine samples subjected to liquid chromatography-mass spectrometry
      measured using two ionization conditions. 

PMID- 25988772
TI  - Pharmacokinetic and pharmacodynamic evaluation of aflibercept for the treatment
      of colorectal cancer.
AB  - INTRODUCTION: Colorectal cancer (CRC) is currently one of the most lethal and
      prevalent tumors worldwide. Prognosis in the metastatic setting remains poor
      despite therapeutic advances. In addition to chemotherapy, new drugs have
      recently been developed targeting signaling pathways involved in tumor growth,
      differentiation and angiogenesis. Aflibercept , a recombinant protein derived
      from VEGF receptors 1 and 2, also targets this angiogenesis pathway but via a
      different mechanism, acting as VEGF decoy, thus blocking other VEGFs. AREAS
      COVERED: A comprehensive review of preclinical studies with aflibercept in cell
      lines and xenografts of different tumor types is presented. Aflibercept safety,
      pharmacokinetics and pharmacodynamics data from Phase I studies in solid tumor
      patients are discussed. Implications of Phase II studies and the pivotal Phase
      III VELOUR trial of second-line treatment in metastatic CRC (mCRC) patients
      evaluating aflibercept alone or combined with chemotherapy are also described.
      EXPERT OPINION: In this challenging field, aflibercept offers a good option for
      oxaliplatin-refractory mCRC patients when combined with irinotecan and 5
      fluorouracil irrespective of prior anti-angiogenic treatment. Therapeutic
      management may be further advanced by characterization of patients with
      predictive biomarkers and molecular profiles to improve benefit with this
      treatment.

PMID- 25988774
TI  - Quality of red blood cells washed using a second wash sequence on an automated
      cell processor.
AB  - BACKGROUND: Washed red blood cells (RBCs) are indicated for immunoglobulin (Ig)A
      deficient recipients when RBCs from IgA-deficient donors are not available.
      Canadian Blood Services recently began using the automated ACP 215 cell processor
      (Haemonetics Corporation) for RBC washing, and its suitability to produce IgA
      deficient RBCs was investigated. STUDY DESIGN AND METHODS: RBCs produced from
      whole blood donations by the buffy coat (BC) and whole blood filtration (WBF)
      methods were washed using the ACP 215 or the COBE 2991 cell processors and IgA
      and total protein levels were assessed. A double-wash procedure using the ACP 215
      was developed, tested, and validated by assessing hemolysis, hematocrit,
      recovery, and other in vitro quality variables in RBCs stored after washing, with
      and without irradiation. RESULTS: A single wash using the ACP 215 did not meet
      Canadian Standards Association recommendations for washing with more than 2 L of
      solution and could not consistently reduce IgA to levels suitable for IgA
      deficient recipients (24/26 BC RBCs and 0/9 WBF RBCs had IgA levels < 0.05
      mg/dL). Using a second wash sequence, all BC and WBF units were washed with more
      than 2 L and had levels of IgA of less than 0.05 mg/dL. During 7 days' postwash
      storage, with and without irradiation, double-washed RBCs met quality control
      criteria, except for the failure of one RBC unit for inadequate (69%) postwash
      recovery. CONCLUSION: Using the ACP 215, a double-wash procedure for the
      production of components for IgA-deficient recipients from either BC or WBF RBCs
      was developed and validated.

PMID- 25988775
TI  - Drug resistance-associated mutations in Mycoplasma genitalium in female sex
      workers, Japan.
AB  - Mycoplasma genitalium was detected in 21 (14.1%) of 149 vaginal swab samples and
      in 1 (0.7%) of 149 throat washing samples from female sex workers during 2013
      2014 in Japan. Prevalences of M. genitalium with macrolide resistance-associated
      23S rRNA mutations and fluoroquinolone resistance-associated parC alterations
      were 47.1% and 36.8%, respectively. 

PMID- 25988776
TI  - Foreword: Pediatric hydrocephalus: systematic literature review and evidence
      based guidelines.

PMID- 25988777
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 1: Introduction and methodology.
AB  - This clinical systematic review of and evidence-based guidelines for the
      treatment of pediatric hydrocephalus were developed by a physician volunteer task
      force. They are provided as an educational tool based on an assessment of current
      scientific and clinical information as well as accepted approaches to treatment.
      They are not intended to be a fixed protocol, because some patients may require
      more or less treatment. In Part 1, the authors introduce the reader to the
      complex topic of hydrocephalus and the lack of consensus on its appropriate
      treatment. The authors describe the development of the Pediatric Hydrocephalus
      Systematic Review and Evidence-Based Guidelines Task Force charged with reviewing
      the literature and recommending treatments for hydrocephalus, and they set out
      the basic methodology used throughout the specific topics covered in later
      chapters. 

PMID- 25988778
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 2: Management of posthemorrhagic hydrocephalus in premature
      infants.
AB  - OBJECT: The objective of this systematic review and analysis was to answer the
      following question: What are the optimal treatment strategies for posthemorrhagic
      hydrocephalus (PHH) in premature infants? METHODS: Both the US National Library
      of Medicine and the Cochrane Database of Systematic Reviews were queried using
      MeSH headings and key words relevant to PHH. Two hundred thirteen abstracts were
      reviewed, after which 98 full-text publications that met inclusion criteria that
      had been determined a priori were selected and reviewed. RESULTS: Following a
      review process and an evidentiary analysis, 68 full-text articles were accepted
      for the evidentiary table and 30 publications were rejected. The evidentiary
      table was assembled linking recommendations to strength of evidence (Classes I
      III). CONCLUSIONS: There are 7 recommendations for the management of PHH in
      infants. Three recommendations reached Level I strength, which represents the
      highest degree of clinical certainty. There were two Level II and two Level III
      recommendations for the management of PHH. Recommendation Concerning Surgical
      Temporizing Measures: I. Ventricular access devices (VADs), external ventricular
      drains (EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are
      treatment options in the management of PHH. Clinical judgment is required.
      STRENGTH OF RECOMMENDATION: Level II, moderate degree of clinical certainty.
      Recommendation Concerning Surgical Temporizing Measures: II. The evidence
      demonstrates that VSG shunts reduce the need for daily CSF aspiration compared
      with VADs. STRENGTH OF RECOMMENDATION: Level II, moderate degree of clinical
      certainty. Recommendation Concerning Routine Use of Serial Lumbar Puncture: The
      routine use of serial lumbar puncture is not recommended to reduce the need for
      shunt placement or to avoid the progression of hydrocephalus in premature
      infants. STRENGTH OF RECOMMENDATION: Level I, high clinical certainty.
      Recommendation Concerning Nonsurgical Temporizing Agents: I. Intraventricular
      thrombolytic agents including tissue plasminogen activator (tPA), urokinase, or
      streptokinase are not recommended as methods to reduce the need for shunt
      placement in premature infants with PHH. STRENGTH OF RECOMMENDATION: Level I,
      high clinical certainty. Recommendation Concerning Nonsurgical Temporizing
      Agents. II. Acetazolamide and furosemide are not recommended as methods to reduce
      the need for shunt placement in premature infants with PHH. STRENGTH OF
      RECOMMENDATION: Level I, high clinical certainty. Recommendation Concerning
      Timing of Shunt Placement: There is insufficient evidence to recommend a specific
      weight or CSF parameter to direct the timing of shunt placement in premature
      infants with PHH. Clinical judgment is required. STRENGTH OF RECOMMENDATION:
      Level III, unclear clinical certainty. Recommendation Concerning Endoscopic Third
      Ventriculostomy: There is insufficient evidence to recommend the use of
      endoscopic third ventriculostomy (ETV) in premature infants with posthemorrhagic
      hydrocephalus. STRENGTH OF RECOMMENDATION: Level III, unclear clinical certainty.

PMID- 25988779
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 3: Endoscopic computer-assisted electromagnetic navigation and
      ultrasonography as technical adjuvants for shunt placement.
AB  - OBJECT: This systematic review was undertaken to answer the following question:
      Do technical adjuvants such as ventricular endoscopic placement, computer
      assisted electromagnetic guidance, or ultrasound guidance improve ventricular
      shunt function and survival? METHODS: The US National Library of Medicine
      PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were
      queried using MeSH headings and key words specifically chosen to identify
      published articles detailing the use of cerebrospinal fluid shunts for the
      treatment of pediatric hydrocephalus. Articles meeting specific criteria that had
      been delineated a priori were then examined, and data were abstracted and
      compiled in evidentiary tables. These data were then analyzed by the Pediatric
      Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to
      consider evidence-based treatment recommendations. RESULTS: The search yielded
      163 abstracts, which were screened for potential relevance to the application of
      technical adjuvants in shunt placement. Fourteen articles were selected for full
      text review. One additional article was selected during a review of literature
      citations. Eight of these articles were included in the final recommendations
      concerning the use of endoscopy, ultrasonography, and electromagnetic image
      guidance during shunt placement, whereas the remaining articles were excluded due
      to poor evidence or lack of relevance. The evidence included 1 Class I, 1 Class
      II, and 6 Class III papers. An evidentiary table of relevant articles was
      created. CONCLUSIONS/RECOMMENDATION: There is insufficient evidence to recommend
      the use of endoscopic guidance for routine ventricular catheter placement.
      STRENGTH OF RECOMMENDATION: Level I, high degree of clinical certainty.
      RECOMMENDATION: The routine use of ultrasound-assisted catheter placement is an
      option. STRENGTH OF RECOMMENDATION: Level III, unclear clinical certainty.
      RECOMMENDATION: The routine use of computer-assisted electromagnetic (EM)
      navigation is an option. STRENGTH OF RECOMMENDATION: Level III, unclear clinical
      certainty.

PMID- 25988780
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 4: Cerebrospinal fluid shunt or endoscopic third ventriculostomy
      for the treatment of hydrocephalus in children.
AB  - OBJECT: The objective of this systematic review was to examine the existing
      literature comparing CSF shunts and endoscopic third ventriculostomy (ETV) for
      the treatment of pediatric hydrocephalus and to make evidence-based
      recommendations regarding the selection of surgical technique for this condition.
      METHODS: Both the US National Library of Medicine and the Cochrane Database of
      Systematic Reviews were queried using MeSH headings and key words specifically
      chosen to identify published articles detailing the use of CSF shunts and ETV for
      the treatment of pediatric hydrocephalus. Articles meeting specific criteria that
      had been determined a priori were examined, and data were abstracted and compiled
      in evidentiary tables. These data were then analyzed by the Pediatric
      Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to
      consider treatment recommendations based on the evidence. RESULTS: Of the 122
      articles identified using optimized search parameters, 52 were recalled for full
      text review. One additional article, originally not retrieved in the search, was
      also reviewed. Fourteen articles met all study criteria and contained comparative
      data on CSF shunts and ETV. In total, 6 articles (1 Class II and 5 Class III)
      were accepted for inclusion in the evidentiary table; 8 articles were excluded
      for various reasons. The tabulated evidence supported the evaluation of CSF
      shunts versus ETV. CONCLUSIONS: Cerebrospinal fluid shunts and ETV demonstrated
      equivalent outcomes in the clinical etiologies studied. RECOMMENDATION: Both CSF
      shunts and ETV are options in the treatment of pediatric hydrocephalus. STRENGTH
      OF RECOMMENDATION: Level II, moderate clinical certainty.

PMID- 25988781
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 5: Effect of valve type on cerebrospinal fluid shunt efficacy.
AB  - OBJECT: The objective of this systematic review was to examine the existing
      literature to compare differing shunt components used to treat hydrocephalus in
      children, find whether there is a superior shunt design for the treatment of
      pediatric hydrocephalus, and make evidence-based recommendations for the
      selection of shunt implants when placing shunts. METHODS: Both the US National
      Library of Medicine PubMed/MEDLINE database and the Cochrane Database of
      Systematic Reviews were queried using MeSH headings and key words chosen to
      identify publications comparing the use of shunt implant components. Abstracts of
      these publications were reviewed, after which studies meeting the inclusion
      criteria were selected. An evidentiary table was compiled summarizing the
      selected articles and quality of evidence. These data were then analyzed by the
      Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task
      Force to consider evidence-based treatment recommendations. RESULTS: Two hundred
      sixty-nine articles were identified using the search parameters, and 43 articles
      were recalled for full-text review. Of these, 22 papers met the study criteria
      for a comparison of shunt components and were included in the evidentiary table.
      The included studies consisted of 1 Class I study, 11 Class II studies, and 10
      Class III studies. The remaining 21 articles were excluded. CONCLUSIONS: An
      analysis of the evidence did not demonstrate a clear advantage for any specific
      shunt component, mechanism, or valve design over another. RECOMMENDATION: There
      is insufficient evidence to demonstrate an advantage for one shunt hardware
      design over another in the treatment of pediatric hydrocephalus. Current designs
      described in the evidentiary tables are all treatment options. STRENGTH OF
      RECOMMENDATION: Level I, high degree of clinical certainty. RECOMMENDATION: There
      is insufficient evidence to recommend the use of a programmable valve versus a
      nonprogrammable valve. Programmable and nonprogrammable valves are both options
      for the treatment of pediatric hydrocephalus. STRENGTH OF RECOMMENDATION: Level
      II, moderate degree of clinical certainty.

PMID- 25988782
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 6: Preoperative antibiotics for shunt surgery in children with
      hydrocephalus: a systematic review and meta-analysis.
AB  - OBJECT: The objective of this systematic review and meta-analysis was twofold: to
      answer the question "What is the evidence for the effectiveness of prophylactic
      intravenous antibiotics for infection prevention in shunt surgery?" and to make
      treatment recommendations based on the available evidence. METHODS: The US
      National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of
      Systematic Reviews were queried using MeSH headings and key words relevant to
      prophylactic antibiotic use in children undergoing a shunt operation. Abstracts
      were reviewed to identify which studies met the inclusion criteria. An
      evidentiary table was assembled summarizing the studies and the quality of
      evidence (Classes I-III). A meta-analysis was conducted using a random-effects
      model to calculate a cumulative estimate of treatment effect using risk ratio
      (RR). Heterogeneity was assessed using chi-square and I(2) statistics. A
      sensitivity analysis was also conducted. Based on the quality of the literature
      and the result of the meta-analysis, a recommendation was rendered (Level I, II,
      or III). RESULTS: Nine studies (4 Class I, 3 Class II, and 2 Class III) met our
      inclusion criteria. Of 7 randomized controlled trials (RCTs), 3 were downgraded
      from Class I to Class II because of significant quality issues, and all RCTs were
      potentially underpowered. In only 2 Class in retrospective cohort studies were
      preoperative antibiotic agents found to be protective against shunt infection.
      When data from the individual studies were pooled together, the infection rate in
      the prophylactic antibiotics group was 5.9% compared with 10.7% in the control
      group. Using a random-effects model, the cumulative RR was 0.55 (95% CI 0.38
      0.81), indicating a protective benefit of prophylactic preoperative intravenous
      antibiotics. A sensitivity analysis of RCTs only (n = 7) also demonstrated a
      statistical benefit, but an analysis of higher-quality RCTs only (n = 4) did not.
      Conclusions Within the limits of this systematic review and meta-analysis,
      administration of preoperative antibiotic agents for shunt surgery in children
      was found to lower the infection risk (quality of evidence: Class II; strength of
      recommendation, Level II). RECOMMENDATION: The use of preoperative antibiotic
      agents can be recommended to prevent shunt infection in patients with
      hydrocephalus. It was only by combining the results of the various underpowered
      studies (meta-analysis) that the use of preoperative antibiotics for shunt
      surgery in children was shown to lower the risk of shunt infection. STRENGTH OF
      RECOMMENDATION: Level II, moderate degree of clinical certainty.

PMID- 25988783
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 7: Antibiotic-impregnated shunt systems versus conventional
      shunts in children: a systematic review and meta-analysis.
AB  - OBJECT: The objective of this systematic review and meta-analysis was to answer
      the following question: Are antibiotic-impregnated shunts (AISs) superior to
      standard shunts (SSs) at reducing the risk of shunt infection in pediatric
      patients with hydrocephalus? METHODS: Both the US National Library of Medicine
      PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were
      queried using MeSH headings and key words relevant to AIS use in children.
      Abstracts were reviewed, after which studies meeting the inclusion criteria were
      selected. An evidentiary table was assembled summarizing the studies and the
      quality of their evidence (Classes I-III). A meta-analysis was conducted using a
      random-effects model to calculate a cumulative estimate of treatment effect using
      risk ratio (RR). Heterogeneity was assessed using the chi-square and I(2)
      statistics. Based on the quality of the literature and the result of the meta
      analysis, a recommendation was rendered (Level I, II, or III). RESULTS: Six
      studies, all Class III, met our inclusion criteria. All but one study focused on
      a retrospective cohort and all but one were conducted at a single institution.
      Four of the studies failed to demonstrate a lowered infection rate with the use
      of an AIS. However, when the data from individual studies were pooled together,
      the infection rate in the AIS group was 5.5% compared with 8.6% in the SS group.
      Using a random-effects model, the cumulative RR was 0.51 (95% CI 0.29-0.89, p <
      0.001), indicating that a shunt infection was 1.96 times more likely in patients
      who received an SS. CONCLUSIONS: We recommend AIS tubing because of the
      associated lower risk of shunt infection compared to the use of conventional
      silicone hardware (quality of evidence: Class III; strength of recommendation:
      Level III). RECOMMENDATION: Antibiotic-impregnated shunt (AIS) tubing may be
      associated with a lower risk of shunt infection compared with conventional
      silicone hardware and thus is an option for children who require placement of a
      shunt. STRENGTH OF RECOMMENDATION: Level III, unclear degree of clinical
      certainty.

PMID- 25988784
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 8: Management of cerebrospinal fluid shunt infection.
AB  - OBJECT: The objective of this systematic review was to answer the following
      question: What is the optimal treatment strategy for CSF shunt infection in
      pediatric patients with hydrocephalus? METHODS: The US National Library of
      Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH
      headings and key words relevant to the objective of this systematic review.
      Abstracts were reviewed, after which studies meeting the inclusion criteria were
      selected and graded according to their quality of evidence (Classes I-III).
      Evidentiary tables were constructed that summarized pertinent study results, and
      based on the quality of the literature, recommendations were made (Levels I-III).
      RESULTS: A review and critical appraisal of 27 studies that met the inclusion
      criteria allowed for a recommendation for supplementation of antibiotic treatment
      using partial (externalization) or complete shunt hardware removal, with a
      moderate degree of clinical certainty. However, a recommendation regarding
      whether complete shunt removal is favored over partial shunt removal (that is,
      externalization) could not be made owing to severe methodological deficiencies in
      the existing literature. There is insufficient evidence to recommend the use of
      intrathecal antibiotic therapy as an adjunct to systemic antibiotic therapy in
      the management of routine CSF shunt infections. This also holds true for other
      clinical scenarios such as when an infected CSF shunt cannot be completely
      removed, when a shunt must be removed and immediately replaced in the face of
      ongoing CSF infection, or when the setting is ventricular shunt infection caused
      by specific organisms (for example, gram-negative bacteria). CONCLUSIONS:
      Supplementation of antibiotic treatment with partial (externalization) or
      complete shunt hardware removal are options in the management of CSF shunt
      infection. There is insufficient evidence to recommend either shunt
      externalization or complete shunt removal as the preferred surgical strategy for
      the management of CSF shunt infection. Therefore, clinical judgment is required.
      In addition, there is insufficient evidence to recommend the combination of
      intrathecal and systemic antibiotics for patients with CSF shunt infection when
      the infected shunt hardware cannot be fully removed, when the shunt must be
      removed and immediately replaced, or when the CSF shunt infection is caused by
      specific organisms. The potential neurotoxicity of intrathecal antibiotic therapy
      may limit its routine use. RECOMMENDATION: Supplementation of antibiotic
      treatment with partial (externalization) or with complete shunt hardware removal
      is an option in the management of CSF shunt infection. STRENGTH OF
      RECOMMENDATION: Level II, moderate degree of clinical certainty. RECOMMENDATION:
      There is insufficient evidence to recommend either shunt externalization or
      complete shunt removal as a preferred surgical strategy for the management of CSF
      shunt infection. Therefore, clinical judgment is required. STRENGTH OF
      RECOMMENDATION: Level III, unclear degree of clinical certainty. RECOMMENDATION:
      There is insufficient evidence to recommend the combination of intrathecal and
      systemic antibiotics for patients with CSF shunt infection in whom the infected
      shunt hardware cannot be fully removed or must be removed and immediately
      replaced, or when the CSF shunt infection is caused by specific organisms. The
      potential neurotoxicity of intrathecal antibiotic therapy may limit its routine
      use. STRENGTH OF RECOMMENDATION: Level III, unclear degree of clinical certainty.

PMID- 25988785
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 9: Effect of ventricular catheter entry point and position.
AB  - OBJECT: The objective of this guideline was to answer the following question: Do
      the entry point and position of the ventricular catheter have an effect on shunt
      function and survival? METHODS: Both the US National Library of Medicine/MEDLINE
      database and the Cochrane Database of Systematic Reviews were queried using MeSH
      headings and key words specifically chosen to identify published articles
      detailing the use of CSF shunts for the treatment of pediatric hydrocephalus.
      Articles meeting specific criteria that had been delineated a priori were then
      examined, and data were abstracted and compiled in evidentiary tables. RESULTS:
      The search yielded 184 abstracts, which were screened for potential relevance to
      the clinical question of the effect of ventricular catheter entry site on shunt
      survival. An initial review of the abstracts identified 14 papers that met the
      inclusion criteria, and these were recalled for full-text review. After review of
      these articles, only 4 were noted to be relevant for an analysis of the impact of
      entry point on shunt survival; an additional paper was retrieved during the
      review of full-text articles and was included as evidence to support the
      recommendation. The evidence included 1 Class II paper and 4 Class III papers. An
      evidentiary table was created including the relevant articles.
      CONCLUSION/RECOMMEndation: There is insufficient evidence to recommend the
      occipital versus frontal point of entry for the ventricular catheter; therefore,
      both entry points are options for the treatment of pediatric hydrocephalus.
      STRENGTH OF RECOMMENDATION: Level III, unclear degree of clinical certainty.

PMID- 25988786
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 10: Change in ventricle size as a measurement of effective
      treatment of hydrocephalus.
AB  - OBJECT: The objective of this systematic review is to answer the following
      question: Does ventricle size after treatment have a predictive value in
      determining the effectiveness of surgical intervention in pediatric
      hydrocephalus? METHODS: The US National Library of Medicine PubMed/MEDLINE
      database and the Cochrane Database of Systematic Reviews were searched using MeSH
      headings and key words relevant to change in ventricle size after surgical
      intervention for hydrocephalus in children. An evidentiary table was assembled
      summarizing the studies and the quality of evidence (Classes I-III). RESULTS: Six
      articles satisfied inclusion criteria for the evidentiary tables for this part of
      the guidelines. All were Class III retrospective studies.
      CONCLUSIONS/RECOMMENDATIon: There is insufficient evidence to recommend a
      specific change in ventricle size as a measurement of the effective treatment of
      hydrocephalus and as a measurement of the timing and effectiveness of treatments
      including ventriculoperitoneal shunts and third ventriculostomies. STRENGTH OF
      RECOMMENDATION: Level III, unclear clinical certainty.

PMID- 25988787
TI  - High current density PQQ-dependent alcohol and aldehyde dehydrogenase bioanodes.
AB  - In this paper, we explore the bioelectrooxidation of ethanol using
      pyrroloquinoline quinone (PQQ)-dependent alcohol and aldehyde dehydrogenase (ADH
      and AldDH) enzymes for biofuel cell applications. The bioanode architectures were
      designed with both direct electron transfer (DET) and mediated electron transfer
      (MET) mechanisms employing high surface area materials such as multi-walled
      carbon nanotubes (MWCNTs) and MWCNT-decorated gold nanoparticles, along with
      different immobilization techniques. Three different polymeric matrices were
      tested (tetrabutyl ammonium bromide (TBAB)-modified Nafion; octyl-modified linear
      polyethyleneimine (C8-LPEI); and cellulose) in the DET studies. The modified
      Nafion membrane provided the best electrical communication between enzymes and
      the electrode surface, with catalytic currents as high as 16.8 +/- 2.1 uA cm(-2).
      Then, a series of ferrocene redox polymers were evaluated for MET. The redox
      polymer 1,1'-dimethylferrocene-modified linear polyethyleneimine (FcMe2-C3-LPEI)
      provided the best electrochemical response. Using this polymer, the
      electrochemical assays conducted in the presence of MWCNTs and MWCNTs-Au
      indicated a Jmax of 781 +/- 59 uA cm(-2) and 925 +/- 68 uA cm(-2), respectively.
      Overall, from the results obtained here, DET using the PQQ-dependent ADH and
      AldDH still lacks high current density, while the bioanodes that operate via MET
      employing ferrocene-modified LPEI redox polymers show efficient energy conversion
      capability in ethanol/air biofuel cells.

PMID- 25988788
TI  - A molecular beacon biosensor based on the nanostructured aluminum oxide surface.
AB  - A new class of molecular beacon biosensors based on the nanostructured aluminum
      oxide or anodic aluminum oxide (AAO) surface is reported. In this type of sensor,
      the AAO surface is used to enhance the fluorescent signals of the fluorophore
      labeled hairpin DNA. When a target DNA with a complementary sequence to that of
      the hairpin DNA is applied on the sensor, the fluorophores are forced to move
      away from the AAO surface due to the hybridization between the hairpin DNA and
      the target DNA, resulting in the significant decrease of the fluorescent signals.
      The observed signal reduction is sufficient to achieve a demonstrated detection
      limit of 10nM, which could be further improved by optimizing the AAO surface. The
      control experiments have also demonstrated that the bioassay used in the
      experiments has excellent specificity and selectivity, indicating the great
      promise of this type of sensor for diagnostic applications. Since the arrayed AAO
      micropatterns can be fabricated on a single chip in a cost-effective manner, the
      arrayed sensors could provide an ideal technical platform for studying
      fundamental biological process and monitoring disease biomarkers. 

PMID- 25988789
TI  - An optimized ratiometric fluorescent probe for sensing human UDP
      glucuronosyltransferase 1A1 and its biological applications.
AB  - This study aimed to develop a practical ratiometric fluorescent probe for highly
      selective and sensitive detection of human UDP-glucuronosyltransferase 1A1
      (UGT1A1), one of the most important phase II enzymes. 4-Hydroxy-1,8-naphthalimide
      (HN) was selected as the fluorophore for this study because it possesses
      intramolecular charge transfer (ICT) feature and displays outstanding optical
      properties. A series of N-substituted derivatives with various hydrophobic,
      acidic and basic groups were designed and synthesized to evaluate the selectivity
      of HN derivatives toward UGT1A1. Our results demonstrated that the introduction
      of an acidic group to HN could significantly improve the selectivity of UGT1A1.
      Among the synthesized fluorescent probes, NCHN (N-3-carboxy propyl-4-hydroxy-1,8
      naphthalimide) displayed the best combination of selectivity, sensitivity and
      ratiometric fluorescence response following UGT1A1-catalyzed glucuronidation.
      UGT1A1-catalyzed NCHN-4-O-glucuronidation generated a single fluorescent product
      with a high quantum yield (Phi=0.688) and brought remarkable changes in both
      color and fluorescence in comparison with the parental substrate. The newly
      developed probe has been successfully applied for sensitive measurements of
      UGT1A1 activities in human liver preparations, as well as for rapid screening of
      UGT1A1 modulators, using variable enzyme sources. Furthermore, its potential
      applications for live imaging of endogenous UGT1A1in cells have also been
      demonstrated. 

PMID- 25988790
TI  - The human counterpart of mouse B-1 cells.
AB  - B-1 cells represent a subpopulation of B cells that has been extensively studied
      in mice and shown to spontaneously generate natural antibody that provides
      antimicrobial protection and helps dispose of cellular debris. Mouse B-1 cells
      originate from distinct progenitors and express additional immune properties that
      include phagocytosis, antigen presentation, immune suppression, and polarization
      of T cell differentiation. Confusion regarding the existence of human B-1 cells
      with mouse B-1-like properties has recently been addressed by identification of a
      new phenotypic profile. Human B-1 cells spontaneously secrete antibody and are
      distinct from other circulating B cell populations by multiple criteria. A number
      of laboratories have recently reported on changes to the human B-1 cell
      population in human disease. 

PMID- 25988791
TI  - On the role of SMA modeling in simulating NiTinol self-expanding stenting
      surgeries to assess the performance characteristics of mechanical and thermal
      activation schemes.
AB  - The work is focused on a detailed simulation of the key stages involved in the
      NiTinol self-expanding stenting surgical procedure; i.e., crimping, deployment,
      SMA activation, as well as post-surgery steady-state cyclic behavior mimicking
      the systolic-to-diastolic pressure oscillations. To this end, a general multi
      mechanism SMA model was utilized, whose calibration was completed using the test
      data from simple isothermal uniaxial tension experiments. The emphasis in the
      study was placed on the comparison of two alternative SMA activation protocols,
      in terms of both the immediate and long-term (post-surgery) performance
      characteristics. The first is 'hard' mechanical activation utilizing
      superelasticity, and the second is 'soft' thermal activation relying upon the
      combined one-way shape memory effect and constrained-recovery characteristics of
      the NiTinol material. The important findings are (1) the thermal activation
      protocol is far superior compared to the mechanical counterpart, from the point
      of view of lower magnitudes of the induced outward chronic forces, lesser
      developed stresses in the host tissue, as well as higher compression ratio with
      lesser crimping force for the same geometry of initial stent memory
      configuration, (2) the thermal activation protocol completely bypassed the
      complications of maintaining the high restraining force during deployment of the
      stent, and (3) there is no indication of any detrimental functional
      fatigue/degradation in the cured stenotic artery during cyclic pressure
      oscillations. 

PMID- 25988792
TI  - Synthesis of antibacterial methacrylate monomer derived from thiazole and its
      application in dental resin.
AB  - A non-quaternary ammonium antibacterial methacrylate monomer MEMT derived from
      thiazole was synthesized and applied into UDMA/TEGDMA dental resin with a series
      of mass fraction (10 wt%, 20 wt%, and 30 wt%). Double bond conversion,
      polymerization shrinkage, water sorption, solubility, flexural strength and
      modulus, and antibacterial activity of MEMT containing resin formulations were
      investigated with UDMA/TEGDMA as control resin. The results showed that MEMT
      containing dental resin had higher double bond conversion than control resin.
      Compared with control polymer, all MEMT containing polymer had comparable or
      lower polymerization shrinkage, water sorption and solubility, except for the
      polymer with 30 wt% of MEMT which had higher water sorption and solubility than
      control polymer. The MEMT had no influence on flexural strength and modulus
      before water immersion, but all MEMT containing polymers had lower flexural
      strength and modulus than control polymer after water immersion. The MEMT could
      endow dental polymer with obvious antibacterial activity by immobilizing MEMT
      into the polymeric network.

PMID- 25988794
TI  - Positive Thinking and Social Perceptions of a Male vs. Female Peer's Cancer
      Experience.
AB  - Positive thinking (PT; i.e., sustaining positive thoughts and suppressing
      negative thoughts to "fight" cancer) is often equated with direct control over
      one's cancer trajectory. It was determined whether PT exposure enhanced the
      effort, control, and responsibility attributions ascribed to a peer for his/her
      cancer trajectory, and whether those ascriptions varied as a function of the
      peer's or participant's gender. Within a hypothetical online blog, a peer
      described a personal experience with bone cancer. Undergraduate participants (N =
      630) were randomly administered one of 12 experimental conditions that varied in
      terms of the peer's gender, PT exposure, and cancer outcome. MANCOVA results
      indicated that PT exposure enhanced the effort, control, and responsibility
      attributions assigned to the peer for an unsuccessful cancer outcome, regardless
      of the peer's or participant's gender. Moreover, the male peer was perceived as
      more accountable for still having cancer but the female peer received more
      "credit" for being cancer-free. The notion of PT may contribute to overestimating
      cancer patients' personal influence over their disease trajectory and social
      perceptions of successful or unsuccessful cancer outcomes vary as a function of
      the patient's gender. 

PMID- 25988793
TI  - Role of cytoreductive nephrectomy for Japanese patients with primary renal cell
      carcinoma in the cytokine and targeted therapy era.
AB  - OBJECTIVE: To assess the efficacy of cytoreductive nephrectomy for Japanese
      patients with primary metastatic renal cell carcinoma in the cytokine and
      targeted therapy era. METHODS: The present retrospective study evaluated 330
      Japanese patients with renal cell carcinoma who had synchronous metastases at
      diagnosis between 2001 and 2010. The characteristics of patients who did and did
      not undergo cytoreductive nephrectomy were compared. RESULTS: Of the 330
      patients, 254 (77.0%) underwent cytoreductive nephrectomy. Patients who underwent
      cytoreductive nephrectomy were younger; had better Karnofsky Performance Status;
      higher rates of lung metastases only and systemic therapy; lower rates of
      increased lactate dehydrogenase concentration and liver and multiple metastases;
      and a lower Memorial Sloan Kettering Cancer Center risk score. Independent
      predictors of poorer overall survival included clinical stage T3/4; poorer
      Memorial Sloan Kettering Cancer Center risk and Karnofsky Performance Status;
      increased C-reactive protein concentration; and absence of cytoreductive
      nephrectomy and systemic therapy. Median overall survival was significantly
      longer in the patients who did rather than did not undergo cytoreductive
      nephrectomy, irrespective of systemic treatment. In patients without
      cytoreductive nephrectomy, median overall survival was significantly longer in
      those who received targeted (15.5 months; hazard ratio 0.45; 95% confidence
      interval 0.21-0.94), but not by cytokine (8.2 months; hazard ratio 0.72; 95%
      confidence interval 0.36-1.46) compared with no systemic treatment (4.4 months).
      CONCLUSIONS: Overall survival seems to be significantly longer in patients
      undergoing cytoreductive nephrectomy. However, prospective trials are required to
      confirm our results, as targeted therapy might improve the survival even in the
      absence of cytoreductive nephrectomy.

PMID- 25988796
TI  - Effect of Preoperative Occlusal Matrices on the Vickers Microhardness of
      Composite Disks Polymerized with QTH and LED Lamps.
AB  - PURPOSE: This study aimed to assess the reliability of the preoperative occlusal
      matrix technique in terms of the surface Vickers microhardness (VMH) of the
      underlying composite restorative material. MATERIALS AND METHODS: Two hundred
      microhybrid composite cylinders were built up and light-cured in a single-layer
      step, forming two experimental groups (N = 100) according to their heights (1.5
      mm/2 mm). Each group was divided into five subgroups (N = 20) depending on the
      matrix thickness (no matrix/0.5 mm/1 mm/2 mm/3 mm). Half the specimens per
      subgroup (N = 10) were randomly polymerized with a quartz-tungsten-halogen (QTH)
      light-curing unit (LCU). The remaining half were cured using a light-emitting
      diode lamp. The top and bottom samples' sides were tested for VMH at 1 hour and
      24 hours post-curing using a universal VMH machine. A multiple analysis of
      variance with repeated measurements for the "surface" factor and the Student
      Newman-Keuls test were run (alpha = 0.05). Bottom/top microhardness ratios were
      compared with the empirically accepted limit (0.8). Surface topography was
      analyzed under a scanning electron microscope. RESULTS: The thinnest matrices
      provided the significantly best VMH values. LCU, disc height, and time also
      contributed to VMH. At 24 hours, 2-mm high discs polymerized with QTH resulted in
      inadequate microhardness ratios when 1-mm thick to 3-mm thick matrices were used.
      CONCLUSION: The thinnest matrices are the most recommendable ones. CLINICAL
      SIGNIFICANCE: The esthetics and occlusal reproducibility achieved with customized
      occlusal matrices fabricated before cavity preparation have been widely
      demonstrated. However, their effect on the physical properties of the
      restorations deserves further investigation. Although more studies are necessary,
      the thinnest matrices seem to be the most suitable to preserve the composite
      surface VMH and the curing depth.

PMID- 25988797
TI  - Myometrial artery calcifications and aging.
AB  - OBJECTIVE: This study aims to determine whether myometrial artery calcifications
      increase with age and whether uterine sections are an appropriate model for
      studying vascular aging. METHODS: An observational study of 172 women (aged 45 y
      or older) who underwent hysterectomy for benign indications at the University
      Hospital (Newark, NJ) between July 1, 2009 and June 1, 2012 was performed. Women
      with a history of malignancy, undocumented last menstrual period, or unavailable
      uterine tissue slides were excluded. H&E-stained uterine sections were evaluated
      for myometrial artery calcifications (defined as the presence of acellular
      densely basophilic material within the media of vessels) by a single pathologist
      in a blinded manner. RESULTS: Between July 1, 2009 and June 1, 2012,
      hysterectomies were performed on 441 women, 172 of whom met inclusion criteria.
      Seventeen women (9.9%) had myometrial artery calcifications detectable on H&E
      stained tissue sections. None of 84 women aged 45 to 49 years, 2 of 51 women
      (3.9%) aged 50 to 59 years (aged 56 and 58 y), 10 of 27 women (37%) aged 60 to 69
      years, and 5 of 10 women (50%) aged 70 to 81 years had myometrial artery
      calcifications. The prevalence of myometrial artery calcifications significantly
      increased with advancing age (P = 0.022). CONCLUSIONS: Myometrial artery
      calcifications increase with advancing age. Histological sections of uterine
      tissue from hysterectomy specimens seem to be a useful model for evaluating
      vascular aging markers.

PMID- 25988799
TI  - A novel FOXL2 gene mutation and BMP15 variants in a woman with primary ovarian
      insufficiency and blepharophimosis-ptosis-epicanthus inversus syndrome.
AB  - OBJECTIVE: This study aims to search for mutations in relevant genes in a woman
      with primary ovarian insufficiency (POI) and blepharophimosis-ptosis-epicanthus
      inversus syndrome (BPES). METHODS: This study reports on the case of a woman with
      POI, BPES, and autoimmune endocrine disorder. Bidirectional sequencing of the
      coding regions and intron/exon boundaries of FOXL2 and BMP15 genes and hormonal
      assays for the measurement of follicle-stimulating hormone, luteinizing hormone,
      estradiol, testosterone, Delta4-androstenedione, and dehydroepiandrosterone
      sulfate were employed. RESULTS: A novel de novo heterozygous deletion
      (p.K150Rfs*121) in the FOXL2 gene was identified to coexist with two BMP15 gene
      variants located in the same allele (c.-9C>G; p.N103S). CONCLUSIONS: The novel,
      de novo FOXL2 gene mutation (p.K150Rfs*121) expands the spectrum of molecular
      defects identified in women with BPES. Coexisting gene variants in POI-related
      genes, such as BMP15, may act synergistically and explain the observed phenotypic
      variability in women with BPES (ie, BPES with or without POI). The concept of
      digenic inheritance suggested herein has been previously introduced for other
      nosologies such as hypogonadotrophic hypogonadism. Endocrine autoimmunity might
      also contribute to the POI phenotype.

PMID- 25988800
TI  - Letters to the Editor.

PMID- 25988798
TI  - kappa Agonists as a novel therapy for menopausal hot flashes.
AB  - OBJECTIVE: The etiology of postmenopausal hot flashes is poorly understood,
      making it difficult to develop and target ideal therapies. A network of
      hypothalamic estrogen-sensitive neurons producing kisspeptin, neurokinin B and
      dynorphin-called KNDy neurons-are located adjacent to the thermoregulatory
      center. KNDy neurons regulate pulsatile secretion of gonadotropin-releasing
      hormone (GnRH) and luteinizing hormone (LH). Dynorphin may inhibit this system by
      binding kappa opioid receptors within the vicinity of KNDy neurons. We
      hypothesize that hot flashes are reduced by KNDy neuron manipulation. METHODS: A
      double-blind, cross-over, placebo-controlled pilot study evaluated the effects of
      a kappa agonist. Hot flash frequency was the primary outcome. Twelve healthy
      postmenopausal women with moderate to severe hot flashes (aged 48-60 y) were
      randomized. Eight women with sufficient baseline hot flashes for statistical
      analysis completed all three interventions: placebo, standard-dose
      pentazocine/naloxone (50/0.5 mg), or low-dose pentazocine/naloxone (25/0.25 mg).
      In an inpatient research setting, each participant received the three
      interventions, in randomized order, on three separate days. On each day, an
      intravenous catheter was inserted for LH blood sampling, and skin conductance and
      Holter monitors were placed. Subjective hot flash frequency and severity were
      recorded. RESULTS: The mean (SEM) hot flash frequency 2 to 7 hours after therapy
      initiation was lower than that for placebo (standard-dose kappa agonist, 4.75
      [0.67] hot flashes per 5 h; low-dose kappa agonist, 4.50 [0.57] hot flashes per 5
      h; placebo, 5.94 [0.78] hot flashes per 5 h; P = 0.025). Hot flash intensity did
      not vary between interventions. LH pulsatility mirrored objective hot flashes in
      some--but not all--women. CONCLUSIONS: This pilot study suggests that kappa
      agonists may affect menopausal vasomotor symptoms.

PMID- 25988801
TI  - A spoonful of sugar.

PMID- 25988802
TI  - Rapid and Specific Aqueous-Phase Detection of Nitroaromatic Explosives with
      Inherent Porphyrin Recognition Sites in Metal-Organic Frameworks.
AB  - Development of a rapid and effective method for the detection of 2,4,6
      trinitrotoluene (TNT) in aqueous phase has attracted great attention. In this
      work, the fluorescent porphyrin-based metal-organic frameworks (MOFs) of PCN-224
      were successfully exploited as a fluorescent probe for the rapid and selective
      TNT detection in water media. This strategy combined the advantages of
      fluorescent porphyrin molecules and porous MOFs, which not only overcame the
      aggregation of hydrophobic tetrakis(4-carboxyphenyl)porphyrin (TCPP) recognition
      sites but also promoted TNT to interact with recognition sites in virtue of the
      high surface and intrinsic open structure of MOFs. As a result, a rapid response
      time of as short as 30 s was obtained for the elaborated fluorescent probe.
      Meanwhile, the bright red emission of porphyrin units in PCN-224 could be
      proportionally quenched in correlation with the applied TNT level through the
      formation of TNT-TCPP complex in the ground state. The specificity of the
      employed sensory platform for TNT recognition was scarcely affected by other
      possible coexistent interfering species. Furthermore, this fluorescent PCN-224
      probe presented a much higher quenching efficiency for TNT than other
      structurally similar nitroaromatic compounds and was successfully applied for the
      quantitative detection of TNT in the mixed nitroaromatic explosive samples. This
      prefigured their great potentials of practical TNT detection in water media for
      public safety and security. 

PMID- 25988803
TI  - Cardiovascular health promotion and consumers with mental illness in Australia.
AB  - People with serious mental illness (SMI) have increased risk of cardiovascular
      disease and premature death, yet research on nurse-provided health promotion in
      mental health services remains under-developed. This paper informs efforts to
      improve the nursing role in physical health of consumers with SMI by establishing
      what nurse perceptions and background influence their care. Members of the
      Australian College of Mental Health Nursing were invited to participate in an
      online survey on their views on physical health care in mental health services.
      Survey questions included: (a) nurse-consumer collaboration in preventative care
      and (b) sub-sections of the Robson and Haddad Physical Health Attitude Scale to
      measure nurse perceived barriers to encouraging lifestyle change of consumers
      with SMI and frequency of nurse physical healthcare practices. Structural
      equation modelling was applied to investigate antecedents to physical health
      care, as well as relationships between antecedents. A national sample of 643
      nurses reported regular engagement in health promotion (e.g. advice on diet).
      There was statistical support for a model depicting perceived consumer-nurse
      collaboration as a dual-determinant of nurse perceived barriers and self-reported
      health promotion to consumers with SMI. Perceived barriers to consumer lifestyle
      change did not predict health promotion. The effects of nurse-consumer
      collaboration were significant, but small. Perceived consumer-nurse collaboration
      in preventative care may positively influence the amount of health promotion by
      nurses in mental health. Perceived barriers to consumer adherence with a healthy
      lifestyle did not have an impact on nurse-delivered health promotion. 

PMID- 25988804
TI  - Abdominoscrotal hydrocele: when one sac becomes bissac.

PMID- 25988795
TI  - Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in
      the EuroSIDA study.
AB  - OBJECTIVES: The long-term side effects of stavudine (d4T) led to recommendations
      in 2009 to phase out use of this drug. We aimed to describe temporal patterns of
      d4T use across Europe. METHODS: Patients taking combination antiretroviral
      therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in
      the study. cART was defined as d4T-containing [d4T plus at least two other
      antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs
      from any class, excluding d4T). Poisson regression was used to describe temporal
      changes in the prevalence of d4T use and factors associated with initiating d4T.
      RESULTS: A total of 5850 patients receiving cART on 1 January 2006 were included
      in the current analysis, rising to 7768 patients on January 1 2013. During this
      time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline
      of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined
      fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in
      Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson
      regression models, new d4T initiations decreased by 14% per 6 months [adjusted
      incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with
      initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98)
      versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60
      6.02) versus HIV RNA < 400 copies/mL. CONCLUSIONS: d4T use has declined sharply
      since 2006 to low levels in most regions; however, a low but persistent level of
      d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also
      more common. The reasons for the regional differences may be multifactorial, but
      it is important to ensure that all clinicians treating HIV-positive patients are
      aware of the potential harmful effects associated with d4T.

PMID- 25988805
TI  - Novel approaches to discovery of biomarkers in rheumatoid arthritis: comment on
      the article by Oswald et al.

PMID- 25988806
TI  - A native interactor scaffolds and stabilizes toxic ATAXIN-1 oligomers in SCA1.
AB  - Recent studies indicate that soluble oligomers drive pathogenesis in several
      neurodegenerative proteinopathies, including Alzheimer and Parkinson disease.
      Curiously, the same conformational antibody recognizes different disease-related
      oligomers, despite the variations in clinical presentation and brain regions
      affected, suggesting that the oligomer structure might be responsible for
      toxicity. We investigated whether polyglutamine-expanded ATAXIN-1, the protein
      that underlies spinocerebellar ataxia type 1, forms toxic oligomers and, if so,
      what underlies their toxicity. We found that mutant ATXN1 does form oligomers and
      that oligomer levels correlate with disease progression in the Atxn1(154Q/+)
      mice. Moreover, oligomeric toxicity, stabilization and seeding require
      interaction with Capicua, which is expressed at greater ratios with respect to
      ATXN1 in the cerebellum than in less vulnerable brain regions. Thus, specific
      interactors, not merely oligomeric structure, drive pathogenesis and contribute
      to regional vulnerability. Identifying interactors that stabilize toxic
      oligomeric complexes could answer longstanding questions about the pathogenesis
      of other proteinopathies. 

PMID- 25988807
TI  - Dysregulated Dscam levels act through Abelson tyrosine kinase to enlarge
      presynaptic arbors.
AB  - Increased expression of Down Syndrome Cell Adhesion Molecule (Dscam) is
      implicated in the pathogenesis of brain disorders such as Down syndrome (DS) and
      fragile X syndrome (FXS). Here, we show that the cellular defects caused by
      dysregulated Dscam levels can be ameliorated by genetic and pharmacological
      inhibition of Abelson kinase (Abl) both in Dscam-overexpressing neurons and in a
      Drosophila model of fragile X syndrome. This study offers Abl as a potential
      therapeutic target for treating brain disorders associated with dysregulated
      Dscam expression. 

PMID- 25988808
TI  - An excitatory amacrine cell detects object motion and provides feature-selective
      input to ganglion cells in the mouse retina.
AB  - Retinal circuits detect salient features of the visual world and report them to
      the brain through spike trains of retinal ganglion cells. The most abundant
      ganglion cell type in mice, the so-called W3 ganglion cell, selectively responds
      to movements of small objects. Where and how object motion sensitivity arises in
      the retina is incompletely understood. In this study, we use 2-photon-guided
      patch-clamp recordings to characterize responses of vesicular glutamate
      transporter 3 (VGluT3)-expressing amacrine cells (ACs) to a broad set of visual
      stimuli. We find that these ACs are object motion sensitive and analyze the
      synaptic mechanisms underlying this computation. Anatomical circuit
      reconstructions suggest that VGluT3-expressing ACs form glutamatergic synapses
      with W3 ganglion cells, and targeted recordings show that the tuning of W3
      ganglion cells' excitatory input matches that of VGluT3-expressing ACs'
      responses. Synaptic excitation of W3 ganglion cells is diminished, and responses
      to object motion are suppressed in mice lacking VGluT3. Object motion, thus, is
      first detected by VGluT3-expressing ACs, which provide feature-selective
      excitatory input to W3 ganglion cells. 

PMID- 25988809
TI  - Drivers' behavioral responses to combined speed and red light cameras.
AB  - BACKGROUND: Numerous signalized intersections worldwide have been equipped with
      enforcement cameras in order to tackle red light running and often also to
      enforce speed limits. However, various impact evaluation studies of red light
      cameras (RLCs) showed an increase of rear-end collisions (up to 44%). OBJECTIVE:
      The principal objective of this study is to provide a better insight in possible
      explaining factors for the increase in rear-end collisions that is caused by
      placing combined speed and red light cameras (SRLCs). METHOD: Real-world
      observations and driving simulator-based observations are combined. Video
      recordings at two signalized intersections where SRLCs were about to be installed
      are used to analyze rear-end conflicts, interactions and driver behavior in two
      conditions (i.e., with and without SRLC). Furthermore, one of these intersections
      was rebuilt in a driving simulator equipped with an eye tracking system. At this
      location, two test conditions (i.e., SRLC and SRLC with a warning sign) and one
      control condition (i.e., no SRLC) are examined. The data of 63 participants were
      used to estimate the risk of rear-end collisions by means of a Monte Carlo
      Simulation. RESULTS: The results of the on-site observation study reveal
      decreases in the number of red and yellow light violations, a shift (i.e., closer
      to the stop line) in the dilemma zone and a time headway reduction after the
      installation of the SRLC. Based on the driving simulator data, the odds of rear
      end collisions (compared to the control condition) for the conditions with SRLC
      and SRLC+warning sign is 6.42 and 4.01, respectively. CONCLUSION: The real-world
      and driving simulator observations indicate that the risk of rear-end collisions
      increases when SRLCs are installed. However, this risk might decrease when a
      warning sign is placed upstream.

PMID- 25988810
TI  - Improving car drivers' perception of motorcycle motion through innovative
      headlight configurations.
AB  - The most frequent cause of motorcycle accidents occurs when another vehicle
      violates the motorcycle's right-of-way at an intersection. In addition to
      detection errors, misperception of the approaching motorcycle's speed and time-to
      arrival is another driver error that accounts for these accidents, although this
      error has been studied less often. Such misperceptions have been shown to be
      related to the small size of motorcycles and to their small angular velocity when
      approaching. In two experiments we tested the impact of different motorcycle
      headlight configurations in various ambient lighting conditions (daytime, dusk,
      and nighttime). The participants drove on a driving simulator and had to turn
      left across a line of vehicles composed of motorcycles and cars. The motorcycles
      were approaching at different speeds and were equipped with either a "standard"
      headlight, a "horizontal" configuration (added to the standard headlight were two
      lights on the rearview mirrors so as to visually increase the horizontal
      dimension of the motorcycle), a "vertical" configuration (one light on the
      rider's helmet and two lights on the fork were added to the standard headlight so
      as to increase the vertical dimension of the motorcycle), or a "combined"
      configuration (combining the horizontal and vertical configurations). The
      findings of the first experiment in nighttime conditions indicated that both the
      vertical and combined configurations significantly increased the gap car drivers
      accepted with respect to the motorcycle as compared to the standard
      configuration, and that the accepted gaps did not differ significantly from those
      accepted for cars. The advantage of the vertical and combined configurations
      showed up especially when the motorcycle's approach speed was high. The findings
      of the second experiment in dusk and daytime conditions indicated similar
      patterns, but the headlight-configuration effect was less pronounced at dusk, and
      nonsignificant during the day. The results are discussed with regards to possible
      applications for motorcycles. 

PMID- 25988812
TI  - Investigating the Interaction Pattern and Structural Elements of a Drug-Polymer
      Complex at the Molecular Level.
AB  - Strong associations between drug and polymeric carriers are expected to
      contribute to higher drug loading capacities and better physical stability of
      amorphous solid dispersions. However, molecular details of the interaction
      patterns and underlying mechanisms are still unclear. In the present study, a
      series of amorphous solid dispersions of clofazimine (CLF), an antileprosy drug,
      were prepared with different polymers by applying the solvent evaporation method.
      When using hypromellose phthalate (HPMCP) as the carrier, the amorphous solid
      dispersion system exhibits not only superior drug loading capacity (63% w/w) but
      also color change due to strong drug-polymer association. In order to further
      explain these experimental observations, the interaction between CLF and HPMCP
      was investigated in a nonpolar volatile solvent system (chloroform) prior to
      forming the solid dispersion. We observed significant UV/vis and (1)H NMR
      spectral changes suggesting the protonation of CLF and formation of ion pairs
      between CLF and HPMCP in chloroform. Furthermore, nuclear Overhauser effect
      spectroscopy (NOESY) and diffusion order spectroscopy (DOSY) were employed to
      evaluate the strength of associations between drug and polymers, as well as the
      molecular mobility of CLF. Finally, by correlating the experimental values with
      quantum chemistry calculations, we demonstrate that the protonated CLF is binding
      to the carboxylate group of HPMCP as an ion pair and propose a possible
      structural model of the drug-polymer complex. Understanding the drug and carrier
      interaction patterns from a molecular perspective is critical for the rational
      design of new amorphous solid dispersions. 

PMID- 25988813
TI  - Induction of influenza (H5N8) antibodies by modified vaccinia virus Ankara H5N1
      vaccine.

PMID- 25988811
TI  - Macrochimerism in Intestinal Transplantation: Association With Lower Rejection
      Rates and Multivisceral Transplants, Without GVHD.
AB  - Blood chimerism has been reported sporadically among visceral transplant
      recipients, mostly in association with graft-vs-host disease (GVHD). We
      hypothesized that a higher degree of mixed chimerism would be observed in
      multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver
      transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal
      prospective study investigating multilineage blood chimerism with flow cytometry
      in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one
      iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9
      iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who
      displayed early moderate to severe rejection. Pre-formed high-titer donor
      specific antibodies, bound in vivo to the circulating donor cells, were
      associated with an accelerated decline in chimerism. Blood chimerism was also
      studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients
      exhibited greater T and B cell chimerism than either iITx or iLTx recipients.
      Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13)
      recipients, suggesting that its presence required the hepatic allograft. Our
      study demonstrates, for the first time, frequent T cell chimerism without GVHD
      following visceral transplantation and a possible relationship with reduced
      rejection rate in MVTx recipients. 

PMID- 25988814
TI  - Association between two single nucleotide polymorphisms of interleukin-27 gene
      and increased cryptorchidism risk.
AB  - Growing evidences have suggested the association between interleukin-27 and
      cryptorchidism. We aimed to investigate the relationship between IL-27
      polymorphisms and cryptorchidism susceptibility. A total of 519 males were
      enrolled in a case-control study (150 cases and 369 normal subjects). The
      variants were discriminated using polymerase chain reaction-restriction fragment
      length polymorphism methods. The proportions of the major allele for rs153109 and
      rs17855750 were A and T with frequencies of 0.56 and 0.85 in cases and 0.51 and
      0.91 in controls respectively (P values = 0.002, P value = 0.002). The
      heterozygous genotype of rs153109 and 17855750 was A/G and T/G with frequencies
      of 0.62 and 0.25 in cases and 0.39 and 0.17 in controls respectively (P values
      <0.001, P values <0.001). The A allele and A/G genotype of rs153109 polymorphisms
      contribute to increase cryptorchidism susceptibility, and G allele and T/G
      genotype of rs17855750 also contribute to increase cryptorchidism susceptibility,
      which implies that these allele and genotypes may be risk factors for the
      development of cryptorchidism. 

PMID- 25988815
TI  - Gold nanoparticles-based chemiluminescence resonance energy transfer for
      ultrasensitive detection of melamine.
AB  - A turn-on chemiluminescence resonance energy transfer method was fabricated for
      the determination of melamine by using bis(2,4,6-trichlorophenyl)oxalate-hydrogen
      peroxide-fluorescein chemiluminescence reaction as a donor and dispersed gold
      nanoparticles as an acceptor. The chemiluminescence signal of bis(2,4,6
      trichlorophenyl)oxalate-hydrogen peroxide-fluorescein reaction decreased
      significantly in the presence of dispersed gold nanoparticles because the
      absorption band of dispersed gold nanoparticles perfectly overlapped with the
      chemiluminescence spectrum. Melamine could induce the aggregation of gold
      nanoparticles, leading to a dramatic red-shift of the absorption band of
      dispersed gold nanoparticles. The absorption band of the aggregated gold
      nanoparticles does not overlap with the chemiluminescence spectrum of the
      reaction. In such a case, chemiluminescence resonance energy transfer could not
      happen and the chemiluminescence signal was restored. The procedure allowed the
      measurement of 3.2*10(-12)-3.2*10(-7) mol/L melamine with a limit of detection of
      3*10(-13) mol/L. The method was applied to the determination of melamine in
      spiked milk samples; with recoveries within the range 94.1-104.2%.

PMID- 25988816
TI  - Bio-inspired route for the synthesis of spherical shaped MgO:Fe(3+)
      nanoparticles: Structural, photoluminescence and photocatalytic investigation.
AB  - MgO:Fe(3+) (0.1-5 mol%) nanoparticles (NPs) were synthesized via eco-friendly,
      inexpensive and simple low temperature solution combustion route using Aloe vera
      gel as fuel. The final products were characterized by SEM, TEM and HRTEM. PXRD
      data and Rietveld analysis revealed the formation of cubic system. The influence
      of Fe(3+) ion concentration on the structure morphology, UV absorption, PL
      emission and photocatalytic activity of MgO:Fe(3+) NPs were investigated. The
      yellow emission with CIE chromaticity coordinates (0.44, 0.52) and average
      correlated color temperature value was found to be 3540 K which corresponds to
      warm light of NPs. The control of Fe(3+) on MgO matrix influences the
      photocatalytic decolorization of methylene blue (MB) under UV light. The enhanced
      photocatalytic activity of MgO:Fe(3+) (4 mol%) was attributed to dopant
      concentration, effective crystallite size, textural properties, decreased band
      gap and capability for reducing the electron-hole pair recombination. Further,
      the trends of inhibitory effect in the presence of different radical scavengers
      were explored. These findings open up new avenues for the exploration of Fe-doped
      MgO in eco-friendly water applications and in the process of display devices.

PMID- 25988817
TI  - Spectroscopic analyses on interaction of melamine, cyanuric acid and uric acid
      with DNA.
AB  - In this work, the interaction of DNA with melamine (MEL), cyanuric acid (CYA) and
      uric acid (UA) were studied, respectively, by means of UV-vis, fluorescence,
      circular dichroism (CD) spectroscopy, viscosity and gel electrophoresis methods.
      The fluorescence quenching was used to study the interaction models of MEL, CYA
      and UA with DNA, respectively, and the bimolecular quenching constant (Kq),
      apparent quenching constant (Ksv), effective binding constant (KA) and
      corresponding dissociation constant (KD) and binding site number (n) were
      calculated by adopting Stern-Volmer, Lineweaver-Burk and Double logarithm
      equations. The results show that MEL, CYA and UA are all able to markedly bind to
      DNA, and the binding strength order is DNA-UA>DNA-CYA>DNA-MEL. It is wished that
      these researches would facilitate the understanding of the formation of kidney
      stones and gout in the body after ingesting excess MEL. 

PMID- 25988818
TI  - Spectroscopic investigation, photophysical parameters and DFT calculations of
      4,4'-(1E,1'E)-2,2'-(pyrazine-2,5-diyl)bis(ethene-2,1-diyl)bis(N,N
      dimethylaniline) (PENDA) in different solvents.
AB  - A comprehensive investigation on the photophysics of a pi-conjugated potential
      push-pull chromophore system 4,4'-(1E,1'E)-2,2'-(Pyrazine-2,5-diyl)bis(ethene-2,1
      diyl)bis(N,N-dimethylaniline) (PENDA) has been carried out spectroscopically. The
      optical absorption and emission properties of this molecule have been studied in
      different solvents. The molecule PENDA shows strong solvatochromic emission upon
      changing the solvent polarity from nonpolar to polar; indicating that emission
      state is of intramolecular charge transfer (ICT) character. The solvent effect on
      the spectral properties such as singlet absorption, molar absorptivity,
      oscillator strength, dipole moment and fluorescence quantum yield of PENDA have
      been studied in detail. Lippert-Mataga and Reichardt correlations were used to
      estimate the difference between the excited and ground state dipole moments
      (DeltaMU). Ground and electronic excited states geometric optimizations were
      performed using density functional theory (DFT) and time-dependent density
      functional theory (TDDFT), respectively, with the Gaussian 09 package. A solution
      of (8*10(-5) M) PENDA in THF, dioxane, CH3CN and CHCl3 gives laser emission when
      pumped by a nitrogen laser pulse (lambdaex=337.1 nm) of 800 ps duration and 1.48
      mJ pulse energy. PENDA dye displays fluorescence quenching by colloidal silver
      nanoparticles (Ag NPs) in ethanol. The fluorescence data reveal that dynamic
      quenching and energy transfer play a major role in the fluorescence quenching
      mechanism.

PMID- 25988819
TI  - Anticancer, photoluminescence and electrochemical properties of structurally
      characterized two imine derivatives.
AB  - Two imine compounds, 4-[(E)-(2-methoxybenzylidene)amino]phenol (L(1)) and 4-[(E)
      (3,4-dimethoxybenzylidene)amino]phenol (L(2)) were synthesized and characterized
      by the analytical and spectroscopic methods. The electrochemical and
      photoluminescence properties of the imine compounds L(1) and L(2) were
      investigated in different solvents. The compounds L(1) and L(2) show different
      redox processes at some potentials. The molecular structures of two Schiff base
      compounds are broadly similar, differing principally in the position, the number
      of methoxy (-OCH3) groups and dihedral angles between aromatic rings. While the
      compound L(1) has only one methoxy group located on the o-position with respect
      to the imine bond (C=N), the L(2) contains two methoxy groups on the p-m
      positions with respect to the imine bond. The imine compounds show two or three
      emission bands in the 619-832 nm range in organic solvents. In the 1.0*10(-3) M
      concentration, the compounds have the highest excitation and emission bands. The
      imine compounds L(1) and L(2) were screened for their in vitro cytotoxicity on
      HeLa cell lines using the xCELLigence system (Real Time Cell Analyzer).

PMID- 25988820
TI  - Molecular Subsetting of Interferon Pathways in Sjogren's Syndrome.
AB  - OBJECTIVE: Sjogren's syndrome (SS) is an autoimmune disease that targets the
      salivary and lacrimal glands. While all patients demonstrate inflammatory
      infiltration and abnormal secretory function in the target tissues, the disease
      features, pathology, and clinical course can vary. Activation of distinct
      inflammatory pathways may drive disease heterogeneity. The purpose of this study
      was to investigate whether activation of the interferon (IFN) pathway correlates
      with key phenotypic features. METHODS: Clinical data and 1 labial salivary gland
      (stored frozen) were obtained from each of 82 participants (53 patients with
      primary SS and 29 control subjects) in the Sjogren's International Collaborative
      Clinical Alliance (SICCA) registry. Salivary gland lysates were immunoblotted
      with markers of type I or type II IFN, and patterns of IFN activity were
      determined by hierarchical clustering. Correlations between SS phenotypic
      features and IFN activity in the salivary gland were performed. RESULTS: A total
      of 58% of the SS participants had high IFN activity and differed significantly
      from those with low IFN activity (higher prevalence of abnormal findings on
      sialometry, leukopenia, hyperglobulinemia, high-titer antinuclear antibody, anti
      SSA, and high focus score on labial salivary gland [LSG] biopsy). Three distinct
      patterns of IFN were evident: type I-predominant, type II-predominant, and type
      I/II mixed IFN. These groups were clinically indistinguishable except for the LSG
      focus score, which was highest in those with type II-predominant IFN. CONCLUSION:
      The SS phenotype includes distinct molecular subtypes, which are segregated by
      the magnitude and pattern of IFN responses. Associations between IFN pathways and
      disease activity suggest that IFNs are relevant therapeutic targets in SS.
      Patients with distinct patterns of high IFN activity are clinically similar,
      demonstrating that IFN-targeting therapies must be selected according to the
      specific pathway(s) that is active in vivo in the individual patient.

PMID- 25988821
TI  - Production of sulfate radical and hydroxyl radical by reaction of ozone with
      peroxymonosulfate: a novel advanced oxidation process.
AB  - In this work, simultaneous generation of hydroxyl radical (*OH) and sulfate
      radical (SO4*-) by the reaction of ozone (O3) with peroxymonosulfate (PMS; HSO5-)
      has been proposed and experimentally verified. We demonstrate that the reaction
      between the anion of PMS (i.e.,SO52-) and O3 is primarily responsible for driving
      O3 consumption with a measured second order rate constant of (2.12 +/- 0.03) *
      10(4) M(-1) s(-1). The formation of both *OH and SO4*- from the reaction between
      SO52- and O3 is confirmed by chemical probes (i.e., nitrobenzene for *OH and
      atrazine forb oth *OH and SO4*-). The yields of *OH and SO4*- are determined to
      be 0.43 +/- 0.1 and 0.45 +/- 0.1 per mol of O3 consumption, respectively. An
      adduct,-O3SOO- + O3 -> -O3SO5-, is assumed as the first step, which further
      decomposes into SO5*- and O3*-. The subsequent reaction of SO5*- with O3is
      proposed to generate SO4*-, while O3*- converts to *OH. A definition of R(ct,*OH)
      and R(ct,SO4*-) (i.e., respective ratios of *OH and SO4*- exposures to O3
      exposure) is adopted to quantify relative contributions of *OH and SO4*-.
      Increasing pH leads to increases in both values of R(ct,*OH) and R(ct,SO4*-) but
      does not significantly affect the ratio of R(ct,SO4*-) to R(ct,*OH) (i.e.,
      R(ct,SO4*-)/R(ct,*OH)), which represents the relative formation of SO4*- to *OH.
      The presence of bicarbonate appreciably inhibits the degradation of probes and
      fairly decreases the relative contribution of *OH for their degradation, which
      may be attributed to the conversion of both *OH and SO4*- to the more selective
      carbonate radical (CO3*-).Humic acid promotes O3 consumption to generate *OH and
      thus leads to an increase in the R(ct,*OH) value in the O3/PMS process,w hile
      humic acid has negligible influence on the R(ct,SO4*-) value. This discrepancy is
      reasonably explained by the negligible effect of humic acid on SO4*- formation
      and a lower rate constant for the reaction of humic acid with SO4*- than with
      *OH. In addition, the efficacy of the O3/PMS process in real water is also
      confirmed.

PMID- 25988822
TI  - Opportunistic fungal infections in dogs treated with ciclosporin and
      glucocorticoids: eight cases.
AB  - Glucocorticoids are the standard of care for the treatment of immune-mediated
      disorders, and ciclosporin is increasingly being used off-label as an adjunct
      immunosuppressive drug in dogs. However, opportunistic infections can develop
      during combination immunosuppressive regimens. This case series describes
      atypical fungal infections in eight dogs treated with immunosuppressive dosages
      of glucocorticoids and ciclosporin. The median duration of combined treatment
      prior to the identification of fungal infection was 31 (range, 13 to 201) days,
      although two dogs received glucocorticoids for prolonged periods prior to the
      addition of ciclosporin. The estimated prevalence of serious fungal infections
      with this drug combination appears to be low (approximately 1 . 67%), but these
      infections led directly or indirectly to death or euthanasia in five of eight
      (63%) dogs. These cases highlight the need for frequent clinical monitoring of
      dogs receiving immunosuppressive dosages of glucocorticoids and ciclosporin.

PMID- 25988823
TI  - A Plea to Consider the Benefits of Moderate Alcohol Consumption.

PMID- 25988824
TI  - Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in
      Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology
      Registry.
AB  - OBJECTIVE: Uveitis is a major extraarticular quality of life-restricting
      manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to
      describe the occurrence of uveitis in JIA patients receiving tumor necrosis
      factor inhibitors or methotrexate (MTX). METHODS: Patients' characteristics,
      treatment, and the reported first occurrence of uveitis as an adverse event were
      searched in the Biologics in Pediatric Rheumatology Registry. The rates per
      exposed patients, exposure time, and time until event were calculated. RESULTS:
      Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844
      patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and
      13 of 364 patients were receiving adalimumab. Patients with uveitis were younger
      (mean +/- SD age 4.6 +/- 4.2 versus 7.4 +/- 4.5 years; P < 0.0001), more likely
      to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P <
      0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with
      a uveitis diagnosis before starting treatment more often had a uveitis event (n =
      28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95%
      confidence interval 1.58-2.94], P < 0.0001). In 16 patients, a new uveitis event
      occurred: 11 while taking MTX (3.2 per 1,000 patient-years), 2 while taking
      etanercept monotherapy (1.9 per 1,000 patient-years), and 3 while taking
      etanercept and MTX combination (0.9 per 1,000 patient-years). A new uveitis event
      occurred early in the disease course after a median disease duration of 1.5 years
      (interquartile range [IQR] 1.3-3.8) while taking etanercept and 1.8 years (IQR
      1.8-2.1) for the MTX cohort. A recurrent uveitis event was reported after a
      disease duration of 7.6 years (IQR 4.3-10.0) in the etanercept cohort and 4.8
      years (IQR 1.0-5.8) in the MTX cohort. Univariate analysis showed that MTX, but
      not etanercept or adalimumab, led to a lower rate of uveitis. CONCLUSION:
      Patients with a history of uveitis had higher risks for uveitis events while
      taking both etanercept and adalimumab. Methotrexate turned out to be protective.
      Few patients developed a first uveitis event while taking etanercept, while the
      rate is comparable to that with MTX. Uveitis may not be attributed to be an
      adverse drug reaction to etanercept.

PMID- 25988825
TI  - Bauxite-supported Transition Metal Oxides: Promising Low-temperature and SO2
      tolerant Catalysts for Selective Catalytic Reduction of NOx.
AB  - In order to develop low-temperature (below 200  degrees C) and SO2-tolerant
      catalysts for selective catalytic reduction (SCR) of NOx, a series of cheap
      M/bauxite (M = Mn, Ni and Cu) catalysts were prepared using bauxite as a support.
      Their SCR performances are much superior to typical V2O5/TiO2, the addition of M
      into bauxite results in significant promotion of NOx removal efficiency,
      especially at low temperature. Among the catalysts, Cu/bauxite exhibits wide
      temperature window over 50-400  degrees C, strong resistance against SO2 and H2O
      as well as good regeneration ability in SCR of NOx. NOx conversion is more than
      80% at 50-200  degrees C, and N2 selectivity is more than 98%. Cu/bauxite can
      serve as a promising catalyst in SCR of NOx. 

PMID- 25988827
TI  - Don't Mind the Gap: Intuitions, Emotions, and Reasons in the Enhancement Debate.

PMID- 25988829
TI  - Genetic diversity of bovine Neospora caninum determined by microsatellite
      markers.
AB  - Neospora caninum is one of the most significant parasitic organisms causing
      bovine abortion worldwide. Despite the economic impact of this infection,
      relatively little is known about the genetic diversity of this parasite. In this
      study, using Nc5 and ITS1 nested PCR, N. caninum has been detected in 12 brain
      samples of aborted fetuses from 298 seropositive dairy cattle collected from four
      different regions in Tehran, Iran. These specimen (Nc-Iran) were genotyped in
      multilocus using 9 different microsatellite markers previously described (MS4,
      MS5, MS6A, MS6B, MS7, MS8, MS10, MS12 and MS21). Microsatellite amplification was
      completely feasible in 2 samples, semi-completely in 8 samples, and failed in 2
      samples. Within the two completely performed allelic profiles of Nc-Iran strains,
      unique multilocus profiles were obtained for both and novel allelic patterns were
      found in the MS8 and MS10 microsatellite markers. The Jaccard's similarity index
      showed significant difference between these two strains and from other standard
      isolates derived from GenBank such as Nc-Liv, Nc-SweB1, Nc-GER1, KBA1, and KBA2.
      All samples originating from the same area showed identical allelic numbers and a
      correlation between the number of repeats and geographic districts was observed. 

PMID- 25988828
TI  - Modulation of the pro-inflammatory molecules E-selectin and TNF-alpha gene
      transcription in Eimeria ninakohlyakimovae-infected primary caprine host
      endothelial cells.
AB  - Eimeria ninakohlyakimovae is an important coccidian parasite of goats which
      causes severe hemorrhagic typhlocolitis in young animals, thereby leading to high
      economic losses in goat industry worldwide. The first merogony of E.
      ninakohlyakimovae occurs within host endothelial cells (ECs) of the lacteal
      capillaries of the villi of the distal ileum resulting in the formation of
      macromeronts (up to 170 MUm) within 10-12 days post-infection (p.i.) and
      releasing >120,000 merozoites I. The E. ninakohlyakimovae-macromeront formation
      within highly immunoreactive host endothelial cells (ECs) should rely on several
      regulatory processes to fulfill this massive replication. Here host EC-parasite
      interactions were investigated to determine the extent of modulation carried out
      by E. ninakohlyakimovae in primary caprine umbilical vein endothelial cells
      (CUVEC) during the first merogony. Gene transcription of the adhesion molecule E
      selectin and the cytokine TNF-alpha were significantly enhanced in the first
      hours and days p.i. in E. ninakohlyakimovae-infected CUVEC. The activation of
      CUVEC was also demonstrated by enhanced chemokine CCL2 and cytokine GM-CSF gene
      transcription, whereas no differences of the eNOS gene transcription were
      observed in E. ninakohlyakimovae-infected CUVEC when compared to un-infected
      controls. The data presented here suggest that infection of caprine host ECs by
      E. ninakohlyakimovae results in EC activation associated with enhanced gene
      transcription encoding for pro-inflammatory as well as immunomodulatory
      molecules, which might be important for the defense against this intracellular
      parasite.

PMID- 25988830
TI  - Zoonotic Cryptosporidium spp. and Enterocytozoon bieneusi in pet chinchillas
      (Chinchilla lanigera) in China.
AB  - Cryptosporidium and Enterocytozoon bieneusi are the most prevalent protist
      pathogens responsible for inducing human and animal diseases worldwide. The aim
      of the present work was to determine the occurrence of Cryptosporidium spp. and
      E. bieneusi in pet chinchillas in China. One hundred forty fecal samples were
      collected from four cities: Beijing, Zhengzhou, Anyang and Guiyang. They were
      then examined with PCR amplification of the small subunit ribosomal RNA (SSU
      rRNA) of Cryptosporidium spp. and the internal transcribed spacer (ITS) of the
      ribosomal RNA of E. bieneusi. The infection rates for Cryptosporidium spp. and E.
      bieneusi were 10.0% and 3.6%, respectively. Sequence analysis of SSU rRNA gene
      products identified two Cryptosporidium spp., Cryptosporidium ubiquitum (n=13)
      and Cryptosporidium parvum (n=1). Subtyping with the 60-kDa glycoprotein (gp60)
      gene showed that all C. ubiquitum isolates belonged to zoonotic subtype family
      XIId, while the subtype of the C. parvum isolate could not be identified. Two E.
      bieneusi genotypes were identified in five samples, zoonotic genotypes BEB6 (n=3)
      and D (n=2). This is the first report of C. ubiquitum and C. parvum, and E.
      bieneusi in chinchillas. This result indicates that pet chinchillas may be a
      potential source of human infection with Cryptosporidium spp. and E. bieneusi. 

PMID- 25988831
TI  - Governing Rule for Dynamic Formation of Grain Boundaries in Grown Graphene.
AB  - Grains and grain boundaries (GBs) in graphene are vital for the control of its
      properties; however, engineering or controlling them by growth remains a great
      challenge. Here we discover that the dynamic formation of GBs within chemical
      vapor deposited polygonal graphene flakes is described by a geometric rule. A GB
      is formed to be symmetrically tilted and a continuous straight line, and the key
      parameters including end point, direction of GB line, and misorientation angles
      between adjacent graphene grains can be determined solely by the geometries of
      the polygonal graphene flakes. We also show the growth control over the length of
      straight graphene GB lines and demonstrate the capability of parallel fabrication
      of field-effect transistor devices across predicted GBs in a straightforward
      manner. This work constitutes a significant step forward in engineering grains
      and GBs in graphene. 

PMID- 25988832
TI  - Post awakening salivary cortisol secretion and trait well-being: The importance
      of sample timing accuracy.
AB  - Indices of post awakening cortisol secretion (PACS), include the rise in cortisol
      (cortisol awakening response: CAR) and overall cortisol concentrations (e.g.,
      area under the curve with reference to ground: AUCg) in the first 30-45 min. Both
      are commonly investigated in relation to psychosocial variables. Although
      sampling within the domestic setting is ecologically valid, participant non
      adherence to the required timing protocol results in erroneous measurement of
      PACS and this may explain discrepancies in the literature linking these measures
      to trait well-being (TWB). We have previously shown that delays of little over 5
      min (between awakening and the start of sampling) to result in erroneous CAR
      estimates. In this study, we report for the first time on the negative impact of
      sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to
      detect significant relationships between PACS and TWB when measured in the
      domestic setting. Healthy females (N=49, 20.5+/-2.8 years) selected for
      differences in TWB collected saliva samples (S1-4) on 4 days at 0, 15, 30, 45 min
      post awakening, to determine PACS. Adherence to the sampling protocol was
      objectively monitored using a combination of electronic estimates of awakening
      (actigraphy) and sampling times (track caps). Relationships between PACS and TWB
      were found to depend on sample timing accuracy. Lower TWB was associated with
      higher post awakening cortisol AUCg in proportion to the mean sample timing
      accuracy (p<.005). There was no association between TWB and the CAR even taking
      into account sample timing accuracy. These results highlight the importance of
      careful electronic monitoring of participant adherence for measurement of PACS in
      the domestic setting. Mean sample timing inaccuracy, mainly associated with
      delays of >5 min between awakening and collection of sample 1 (median=8 min
      delay), negatively impacts on the sensitivity of analysis to detect associations
      between PACS and TWB.

PMID- 25988826
TI  - The opioid receptors as targets for drug abuse medication.
AB  - The endogenous opioid system is largely expressed in the brain, and both
      endogenous opioid peptides and receptors are present in areas associated with
      reward and motivation. It is well known that this endogenous system plays a key
      role in many aspects of addictive behaviours. The present review summarizes the
      modifications of the opioid system induced by chronic treatment with drugs of
      abuse reported in preclinical and clinical studies, as well as the action of
      opioid antagonists and agonists on the reinforcing effects of drugs of abuse,
      with therapeutic perspectives. We have focused on the effects of chronic
      psychostimulants, alcohol and nicotine exposure. Taken together, the changes in
      both opioid peptides and opioid receptors in different brain structures following
      acute or chronic exposure to these drugs of abuse clearly identify the opioid
      system as a potential target for the development of effective pharmacotherapy for
      the treatment of addiction and the prevention of relapse. 

PMID- 25988833
TI  - Analysis of the genetic basis of periodic fever with aphthous stomatitis,
      pharyngitis, and cervical adenitis (PFAPA) syndrome.
AB  - PFAPA syndrome is the most common autoinflammatory syndrome in children from
      Western countries. In spite of its strong familial clustering, its genetic basis
      and inheritance pattern are still unknown. We performed a comprehensive genetic
      study on 68 individuals from 14 families. Linkage analysis suggested a
      susceptibility locus on chromosome 8, but direct molecular sequencing did not
      support this initial statistical finding. Exome sequencing revealed the absence
      of any gene that was mutated in all patients. Exhaustive screening of genes
      involved in other autoinflammatory syndromes or encoding components of the human
      inflammasome showed no DNA variants that could be linked to PFAPA molecular
      pathology. Among these, the previously-reported missense mutation V198M in the
      NLRP3 gene was clearly shown not to co-segregate with PFAPA. Our results on this
      relatively large cohort indicate that PFAPA syndrome is unlikely to be a
      monogenic condition. Moreover, none of the several genes known to be involved in
      inflammation or in autoinflammatory disorders seem to be relevant, alone, to its
      etiology, suggesting that PFAPA results from oligogenic or complex inheritance of
      variants in multiple disease genes and/or non-genetic factors. 

PMID- 25988834
TI  - Impairment of radial glial scaffold-dependent neuronal migration and formation of
      double cortex by genetic ablation of afadin.
AB  - Studies of human brain malformations, such as lissencephaly and double cortex,
      have revealed the importance of neuronal migration during cortical development.
      Afadin, a membrane scaffolding protein, regulates the formation of adherens
      junctions (AJs) and cell migration to form and maintain tissue structures. Here,
      we report that mice with dorsal telencephalon-specific ablation of afadin gene
      exhibited defects similar to human double cortex, in which the heterotopic cortex
      was located underneath the normotopic cortex. The normotopic cortex of the mutant
      mice was arranged in the pattern similar to the cortex of the control mice, while
      the heterotopic cortex was disorganized. As seen in human patients, double cortex
      in the mutant mice was formed by impaired neuronal migration during cortical
      development. Genetic ablation of afadin in the embryonic cerebral cortex
      disrupted AJs of radial glial cells, likely resulting in the retraction of the
      apical endfeet from the ventricular surface and the dispersion of radial glial
      cells from the ventricular zone to the subventricular and intermediate zones.
      These results indicate that afadin is required for the maintenance of AJs of
      radial glial cells and that the disruption of AJs might cause an abnormal radial
      scaffold for neuronal migration. In contrast, the proliferation or
      differentiation of radial glial cells was not significantly affected. Taken
      together, these findings indicate that afadin is required for the maintenance of
      the radial glial scaffold for neuronal migration and that the genetic ablation of
      afadin leads to the formation of double cortex. 

PMID- 25988835
TI  - Modality-independent neural mechanisms for novel phonetic processing.
AB  - The present study investigates whether the inferior frontal gyrus is activated
      for phonetic segmentation of both speech and sign. Early adult second language
      learners of Spanish and American Sign Language at the very beginning of
      instruction were tested on their ability to classify lexical items in each
      language based on their phonetic categories (i.e., initial segments or location
      parameter, respectively). Conjunction analyses indicated that left-lateralized
      inferior frontal gyrus (IFG), superior parietal lobule (SPL), and precuneus were
      activated for both languages. Common activation in the left IFG suggests a
      modality-independent mechanism for phonetic segmentation. Additionally, common
      activation in parietal regions suggests spatial preprocessing of audiovisual and
      manuovisual information for subsequent frontal recoding and mapping. Taken
      together, we propose that this frontoparietal network is involved in domain
      general segmentation of either acoustic or visual signal that is important to
      novel phonetic segmentation. 

PMID- 25988837
TI  - Preparation of proteoglycan from salmon nasal cartilage under nondenaturing
      conditions.
AB  - Salmon nasal cartilage was micronized in ethanol using a rotor-stator homogenizer
      for the high yield of proteoglycan extraction. This procedure also brought about
      depressing the degradation of proteoglycan and the contamination of collagens.
      Proteoglycan was extracted by 4 M magnesium chloride and isolated by anion
      exchange chromatography. The gel filtration HPLC and the antibody reactivity
      showed that the core protein was intact.

PMID- 25988836
TI  - Selective transgene expression in cerebellar Purkinje cells and granule cells
      using adeno-associated viruses together with specific promoters.
AB  - Adeno-associated virus (AAV) is a powerful tool for gene delivery into the brain
      and has been used for transgene expression in the cerebellar cortex. Although the
      efficacies of different AAV serotypes to transduce cerebellar Purkinje cells were
      examined, it has been difficult to achieve cell-type specific transgene
      expression. Here we used AAV serotype 1 with two specific promoters, namely,
      Ca(2+)/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) and the minimum
      region of the GABAA receptor alpha6 subunit (GABRalpha6) promoters, and compared
      their expression patterns in the cerebellar cortex with the expression patterns
      of ubiquitous promoters that are often used for AAV-mediated expression. Whereas
      AAV with ubiquitous promoters, the cytomegalovirus early enhancer/chicken beta
      actin promoter, and a small fragment of the synapsin-1 gene promoter caused
      ubiquitous expression in all cerebellar neurons tested, AAV with the CaMKIIalpha
      promoter injected into 10-day-old mice enabled selective expression in Purkinje
      cells. Furthermore, we developed AAV with the GABRalpha6 promoter, and succeeded
      for the first time to express the transgene exclusively in granule cells. Fresh
      cerebellar slices of mice injected with these AAVs were applicable for
      physiological experiments, such as patch clamp recording, optogenetic imaging,
      and stimulation. Thus, these AAV vectors are useful tools towards understanding
      the basic properties of cerebellar neurons or mechanisms of cerebellar functions.
      Particularly, selective expression in Purkinje or granule cells is useful for
      analyses using genetically-modified animals, such as knockout mice. 

PMID- 25988838
TI  - Introduction of luminescent rhenium(I), ruthenium(II), iridium(III) and
      rhodium(III) systems into rhodamine-tethered ligands for the construction of
      bichromophoric chemosensors.
AB  - Several classes of luminescent transition metal complexes, including rhenium(I)
      tricarbonyl diimine, ruthenium(II) diimine, cyclometallated iridium(III) and
      rhodium(III) diimine, as well as ruthenium(II) and iridium(III) terpyridine
      systems, tethered with rhodamine moieties, have been synthesized and
      characterized. The X-ray crystal structure of one cyclometallated rhodium(III)
      diimine (11) with a rhodamine pendant was determined. Most of the complexes were
      found to exhibit emission in fluid solution at room temperature. Depending on the
      nature of the transition metal system, the emission origin was mainly assigned to
      be derived from the triplet excited state of the metal-to-ligand charge transfer
      ((3)MLCT) or the intraligand ((3)IL) transition. The cation-binding properties of
      these complexes toward various cations were investigated by electronic absorption
      and emission spectroscopy. Some of them were found to exhibit new low-energy
      absorption and emission bands, attributed to the ring opening of the rhodamine
      moiety, with high selectivity and/or high sensitivity for various cations, in
      agreement with sensing and spectroscopic behaviours of the rhodamine derivative.
      Depending on the nature of the transition metal centres, the chelating ligands as
      well as the linker to the rhodamine derivative, different sensing properties in
      terms of selectivity, sensitivity and binding stability, could be obtained.

PMID- 25988839
TI  - Gadolinium nanoparticles and contrast agent as radiation sensitizers.
AB  - The goal of the present study was to evaluate and compare the radiosensitizing
      properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent
      (GdCA) Magnevist((r)) in order to better understand the mechanisms by which they
      act as radiation sensitizers. This was determined following either low energy
      synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells
      exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or
      GdCA. Clonogenic assays were used to quantify cell survival after irradiation in
      the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV
      range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source.
      Radiosensitization was demonstrated with both agents in combination with X
      irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater
      effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy)
      was observed at an energy of 65 keV for both the nanoparticles and the contrast
      agent (2.44   +/-   0.33 and 1.50   +/-   0.20, for GdNPs and GdCA,
      respectively). At a higher energy (1.25 MeV), radiosensitization only was
      observed with GdNPs (1.66   +/-   0.17 and 1.01   +/-   0.11, for GdNPs and GdCA,
      respectively). The radiation dose enhancements were highly 'energy dependent' for
      both agents. Secondary-electron-emission generated after photoelectric events
      appeared to be the primary mechanism by which Gd contrast agents functioned as
      radiosensitizers. On the other hand, other biological mechanisms, such as
      alterations in the cell cycle may explain the enhanced radiosensitizing
      properties of GdNPs.

PMID- 25988840
TI  - Lateralization of mesial temporal lobe epilepsy with chronic ambulatory
      electrocorticography.
AB  - OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically
      undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or
      intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure
      focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with
      MTL epilepsy may provide additional information about seizure lateralization.
      This analysis describes data obtained from chronic ambulatory ECoG in patients
      with suspected bilateral MTL epilepsy in order to assess the time required to
      determine the seizure lateralization and whether this information could influence
      treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with
      suspected bilateral MTL epilepsy who were among a larger cohort with intractable
      epilepsy participating in a randomized controlled trial of responsive
      neurostimulation. Subjects were implanted with bilateral MTL leads and a
      cranially implanted neurostimulator programmed to detect abnormal interictal and
      ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to
      determine the lateralization of electrographic seizures and the interval of time
      until independent bilateral MTL electrographic seizures were recorded. RESULTS:
      Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7
      years on average (median 4.9 years). Independent bilateral MTL electrographic
      seizures were recorded in 84%. The average time to record bilateral
      electrographic seizures in the ambulatory setting was 41.6 days (median 13 days,
      range 0-376 days). Sixteen percent had only unilateral electrographic seizures
      after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the
      subjects implanted with bilateral MTL electrodes required >1 month of chronic
      ambulatory ECoG before the first contralateral MTL electrographic seizure was
      recorded. Some patients with suspected bilateral MTL seizures had only unilateral
      electrographic seizures. Chronic ambulatory ECoG in patients with suspected
      bilateral MTL seizures provides data in a naturalistic setting, may complement
      data from inpatient video-EEG monitoring, and can contribute to treatment
      decisions.

PMID- 25988842
TI  - Increased vulnerability to ethanol consumption in adolescent maternal separated
      mice.
AB  - The purpose of this study was to evaluate the effects of early life stress on the
      vulnerability to ethanol consumption in adolescence. To this aim, mice were
      separated from their mothers for 12 hours/day on postnatal days 8 and 12.
      Emotional behavior (light-dark box, elevated plus maze and tail suspension tests)
      and pre-attentional deficit (pre-pulse inhibition) were evaluated in adolescent
      maternal separated (MS) mice. Alterations of the corticotropin-releasing factor
      (CRF), glucocorticoid receptor (NR3C1), tyrosine hydroxylase (TH), mu-opioid
      receptor (MOr), brain-derived neurotrophic factor (BDNF), neuronal nuclei (NeuN),
      microtubule-associated protein 2 (MAP2) and neurofilament heavy (NF200)
      immunoreactive fibers were studied in the paraventricular nucleus of the
      hypothalamus (PVN), ventral tegmental area (VTA), nucleus accumbens (NAc) or
      hippocampus (HIP). The effects of maternal separation (alone or in combination
      with additional stressful stimuli) on ethanol consumption during adolescence were
      evaluated using the oral ethanol self-administration paradigm. MS mice presented
      mood-related alterations and pre-attentional deficit. Increased CRF, MOr and TH,
      and reduced BDNF, NR3C1, NeuN, MAP2 and NF200-immunoreactive fibers were observed
      in the PVN, NAc and HIP of adolescent MS mice. In the oral ethanol self
      administration test, adolescent MS mice presented higher ethanol consumption and
      motivation. Exposure to additional new stressful stimuli during adolescence
      significantly increased the vulnerability to ethanol consumption induced by
      maternal separation. These results clearly demonstrated that exposure to early
      life stress increased the vulnerability to ethanol consumption, potentiated the
      effects of stressful stimuli exposure during adolescence on ethanol consumption
      and modified the expression of key targets involved in the response to stress,
      ethanol reinforcing properties and cognitive processes.

PMID- 25988841
TI  - Application of high-dimensional feature selection: evaluation for genomic
      prediction in man.
AB  - In this study, we investigated the effect of five feature selection approaches on
      the performance of a mixed model (G-BLUP) and a Bayesian (Bayes C) prediction
      method. We predicted height, high density lipoprotein cholesterol (HDL) and body
      mass index (BMI) within 2,186 Croatian and into 810 UK individuals using genome
      wide SNP data. Using all SNP information Bayes C and G-BLUP had similar
      predictive performance across all traits within the Croatian data, and for the
      highly polygenic traits height and BMI when predicting into the UK data. Bayes C
      outperformed G-BLUP in the prediction of HDL, which is influenced by loci of
      moderate size, in the UK data. Supervised feature selection of a SNP subset in
      the G-BLUP framework provided a flexible, generalisable and computationally
      efficient alternative to Bayes C; but careful evaluation of predictive
      performance is required when supervised feature selection has been used. 

PMID- 25988843
TI  - Programmable living material containing reporter micro-organisms permits
      quantitative detection of oligosaccharides.
AB  - The increasing molecular understanding of many diseases today permits the
      development of new diagnostic methods. However, few easy-to-handle and
      inexpensive tools exist for common diseases such as food disorders. Here we
      present a living material based analytical sensor (LiMBAS) containing genetically
      modified bacteria (Escherichia coli) immobilized and protected in a thin layer
      between a nanoporous and support polymer membrane for a facile quantification of
      disease-relevant oligosaccharides. The bacteria were engineered to fluoresce in
      response to the analyte to reveal its diffusion behavior when using a blue-light
      source and optical filter. We demonstrated that the diffusion zone diameter was
      related semi-logarithmically to the analyte concentration. LiMBAS could
      accurately quantify lactose or galactose in undiluted food samples and was able
      to measure food intolerance relevant concentrations in the range of 1-1000 mM
      requiring a sample volume of 1-10 MUL. LiMBAS was storable for at least seven
      days without losing functionality at 4  degrees C. A wide range of genetic tools
      for E. coli are readily available thus allowing the reprogramming of the material
      to serve as biosensor for other molecules. In combination with smartphones, an
      automated diagnostic analysis becomes feasible which would also allow untrained
      people to use LiMBAS. 

PMID- 25988844
TI  - Complementary effects of bevacizumab and MMC in the improvement of surgical
      outcome after glaucoma filtration surgery.
AB  - PURPOSE: To determine the optimum administration route of bevacizumab after
      glaucoma filtering surgery (GFS) and to investigate whether a reduced dose of
      mitomycin-C (MMC) in combination with bevacizumab could improve surgical outcome
      with a reduced incidence of side-effects. METHODS: Plasma levels of bevacizumab
      were determined via ELISA after intracameral (IC), subconjunctival (SC) and
      intravitreal (IV) injections in mice, subjected to a mouse model of GFS.
      Application of MMC was compared to bevacizumab (SC, 25 MUg) and to the combined
      use of both adjuvants. Surgical sponges soaked in MMC 0.02% or 0.01% were exposed
      to the sclera for 1 or 2 min. Treatment outcome was studied by bleb
      investigation. RESULTS: The three administration routes of bevacizumab equally
      improved surgical outcome. The VEGF antibody was detected at relatively high
      levels in plasma shortly after IV injection, whereas it was minimally absorbed
      after IC and SC injections. Both bevacizumab (SC) and MMC 0.02% (2 min) similarly
      increased bleb area. As compared to MMC, the combined injection with bevacizumab
      induced an additional effect on surgical outcome. Exposure of MMC 0.02% for 1 or
      2 min together with bevacizumab equally improved surgical outcome, but 2 min
      application induced corneal toxicity. The combined use of bevacizumab and 1-min
      MMC 0.01% also improved surgical outcome compared to monotherapy, although to a
      lesser extent than the combination with 1-min MMC 0.02%. CONCLUSIONS: Adjunctive
      bevacizumab not only enhances the beneficial effect of MMC on surgical outcome,
      but also allows reducing the administration time of MMC 0.02%, thereby
      eliminating its toxic effects on the cornea.

PMID- 25988845
TI  - The effects of preparation and acoustic stimulation on contralateral and
      ipsilateral corticospinal excitability.
AB  - A loud auditory stimulus (LAS) presented together with an imperative stimulus
      during preparation for motor actions can speed their initiation. The effects of
      LAS on corticospinal excitability (CSE), however, depend on the state of
      preparation of the motor system for action. CSE also depends on the brain
      hemisphere controlling the responding limb. Usually, CSE is increased just before
      movement onset in the hemisphere controlling the movement and inhibited on the
      other side. This study investigated the impact of LAS on CSE of the contralateral
      and ipsilateral hemispheres, while participants prepared for a voluntary
      abduction of the index finger. In Experiment 1, we attempted to identify the
      pattern of modulation of the ipsilateral cortex (resting side) by determining the
      time course of corticospinal changes in anticipatory timing actions using
      transcranial magnetic stimulation. In Experiment 2, we investigated the impact of
      LAS on the ipsilateral and contralateral CSE during anticipatory preparation.
      Results found no modulation of ipsilateral CSE during preparation, but indicate
      an increase in CSE after EMG onset on the acting limb. Moreover, we found that
      LAS presentation increased CSE on the contralateral side (active side). 

PMID- 25988846
TI  - Hydrothermally Grown In-doped ZnO Nanorods on p-GaN Films for Color-tunable
      Heterojunction Light-emitting-diodes.
AB  - The incorporation of doping elements in ZnO nanostructures plays an important
      role in adjusting the optical and electrical properties in optoelectronic
      devices. In the present study, we fabricated 1-D ZnO nanorods (NRs) doped with
      different In contents (0% ~ 5%) on p-GaN films using a facile hydrothermal
      method, and investigated the effect of the In doping on the morphology and
      electronic structure of the NRs and the electrical and optical performances of
      the n-ZnO NRs/p-GaN heterojunction light emitting diodes (LEDs). As the In
      content increased, the size (diameter and length) of the NRs increased, and the
      electrical performance of the LEDs improved. From the electroluminescence (EL)
      spectra, it was found that the broad green-yellow-orange emission band
      significantly increased with increasing In content due to the increased defect
      states (oxygen vacancies) in the ZnO NRs, and consequently, the superposition of
      the emission bands centered at 415 nm and 570 nm led to the generation of white
      light. These results suggest that In doping is an effective way to tailor the
      morphology and the optical, electronic, and electrical properties of ZnO NRs, as
      well as the EL emission property of heterojunction LEDs. 

PMID- 25988847
TI  - Fatigue two months after myocardial infarction and its relationships with other
      concurrent symptoms, sleep quality and coping strategies.
AB  - AIMS AND OBJECTIVES: To explore fatigue levels two months after myocardial
      infarction and examine the associations with other concurrent symptoms, sleep
      quality and coping strategies. BACKGROUND: Fatigue has been found to be the most
      frequent and bothersome symptom after myocardial infarction, influencing health
      related quality of life negatively. DESIGN: The present study was explorative and
      cross-sectional. The focus was on fatigue two months postmyocardial infarction,
      complemented with a comparative analysis of fatigue dimension levels. METHODS:
      The sample included 142 persons (mean age 63 years), treated for myocardial
      infarction, who responded to a questionnaire package measuring fatigue,
      depression, health complaints (symptoms), sleep quality and coping strategies.
      RESULTS: The main results showed that a global fatigue score two months
      postmyocardial infarction was associated with concurrent symptoms, such as
      breathlessness and stress, and coping strategies such as change in values,
      intrusion and isolation. In comparisons of present fatigue dimension levels
      (general fatigue, physical fatigue, reduced activity and mental fatigue) two
      months postmyocardial infarction with baseline measurements (first week in
      hospital), the results showed that levels of fatigue dimensions had decreased. In
      comparisons with levels of fatigue four months postmyocardial infarction in a
      reference group, we found lower levels of fatigue two months postmyocardial
      infarction. CONCLUSION: The present findings indicated that postmyocardial
      infarction fatigue is lowest two months postmyocardial infarction. This may thus
      be the right time to identify persons experiencing postmyocardial infarction
      fatigue, as timely fatigue relief support may prevent progression into a state of
      higher levels of fatigue. RELEVANCE TO CLINIC PRACTICE: Measuring fatigue two
      months postmyocardial infarction would enable healthcare professionals to
      identify persons experiencing fatigue and to introduce fatigue relief support.
      Tailored rehabilitation support should include stress management and
      breathlessness relief support. If maladaptive use of the coping strategies
      isolation and intrusion is observed, these strategies could be discussed together
      with the patient.

PMID- 25988848
TI  - Desmopressin treatment improves platelet function under flow in patients with
      postoperative bleeding.
AB  - BACKGROUND: Patients undergoing major cardiothoracic surgery are subjected to
      dilution, owing to massive fluid infusion and blood component transfusion. These
      patients may experience bleeding perioperatively, and are frequently treated with
      the endothelium-activating agent desmopressin. OBJECTIVES: To investigate the
      effect of desmopressin administration on von Willebrand factor (VWF)-dependent
      coagulant and platelet functions under flow conditions. PATIENTS/METHODS: Blood
      from 16 patients with postoperative bleeding was obtained before and after
      desmopressin treatment (0.3 MUg kg(-1) body weight), and assessed for coagulant
      properties and platelet function. Furthermore, VWF antigen levels and multimer
      composition were determined in both samples. RESULTS: Desmopressin treatment did
      not change thrombin generation in plasma or whole blood thromboelasticity. Also
      coagulation factor levels (other than factor VIII) and coagulation times were
      unchanged, suggesting that desmopressin treatment did not have a major effect on
      the coagulant activity. On the other hand, desmopressin treatment raised the
      already high plasma levels of VWF from a median of 116 IU mL(-1) (interquartile
      range [IQR] 102-154 IU mL(-1) ) to a median of 160 IU mL(-1) (IQR 126-187 IU mL(
      1) ) (P = 0.007), owing to accumulation of the high molecular weight VWF
      multimers. Furthermore, desmopressin treatment caused an increase in collagen
      dependent thrombus formation and platelet phosphatidylserine exposure. Markers of
      thrombus formation correlated with the plasma levels of VWF. In vitro control
      experiments confirmed a major contribution of VWF to thrombus formation and
      procoagulant activity under conditions of blood dilution. CONCLUSIONS:
      Desmopressin treatment of patients with bleeding complications after
      cardiothoracic surgery induces the release of high molecular weight VWF
      multimers, which enhance platelet activation and thrombus formation under flow
      conditions.

PMID- 25988849
TI  - Recent developments in atmospheric pressure photoionization-mass spectrometry.
AB  - Recent developments in atmospheric pressure photoionization (APPI), which is one
      of the three most important ionization techniques in liquid chromatography-mass
      spectrometry, are reviewed. The emphasis is on the practical aspects of APPI
      analysis, its combination with different separation techniques, novel
      instrumental developments - especially in gas chromatography and ambient mass
      spectrometry - and the applications that have appeared in 2009-2014. (c) 2015
      Wiley Periodicals, Inc. Mass Spec Rev 36:423-449, 2017.

PMID- 25988850
TI  - NO disproportionation at a mononuclear site-isolated Fe(2+) center in Fe(2+)-MOF
      5.
AB  - The weak-field ligand environments at the metal nodes of metal-organic frameworks
      (MOFs) mimic the electronic environment of metalloenzyme active sites, but little
      is known about the reactivity of MOF nodes toward small molecules of biological
      relevance. Here, we report that the ferrous ions in Fe(2+)-exchanged MOF-5
      disproportionate nitric oxide to produce nitrous oxide and a ferric nitrito
      complex. Although mechanistic studies of N-N bond forming transformations often
      invoke a hyponitrite species, as in nitric oxide reductase and NOx reduction
      catalysis, little is known about this intermediate in its monoanionic state.
      Together with the first report of N-N coupling between NO molecules in a MOF, we
      present evidence for a species that is consistent with a ferric hyponitrite
      radical, whose isolation is enabled by the spatial constraints of the MOF matrix.

PMID- 25988851
TI  - Middle Managers' Experiences and Role in Implementing an Interactive Tailored
      Patient Assessment eHealth Intervention in Clinical Practice.
AB  - The role of nurse and physician managers is considered crucial for implementing
      eHealth interventions in clinical practice, but few studies have explored this.
      The aim of the current study was to examine the perceptions of nurse and
      physician managers regarding facilitators, barriers, management role,
      responsibility, and action taken in the implementation of an eHealth intervention
      called Choice into clinical practice. Individual qualitative interviews were
      conducted with six nurses and three physicians in management positions at five
      hospital units. The findings revealed that nurse managers reported
      conscientiously supporting the implementation, but workloads prevented them from
      participating in the process as closely as they wanted. Physician managers
      reported less contribution. The implementation process was influenced by
      facilitating factors such as perceptions of benefits from Choice and use of
      implementation strategies, along with barriers such as physician resistance,
      contextual factors and difficulties for front-line providers in learning a new
      way of communicating with the patients. The findings suggest that role
      descriptions for both nurse and physician managers should include implementation
      knowledge and implementation skills. Managers could benefit from an
      implementation toolkit. Implementation management should be included in
      management education for healthcare managers to prepare them for the constant
      need for implementation and improvement in clinical practice. 

PMID- 25988852
TI  - Controlling the dynamics of Forster resonance energy transfer inside a tunable
      sub-wavelength Fabry-Perot-resonator.
AB  - In this study we examined the energy transfer dynamics of a FRET coupled pair of
      chromophores at the single molecule level embedded in a tunable sub-wavelength
      Fabry-Perot resonator with two silver mirrors and separations in the lambda/2
      region. By varying the spectral mode density in the resonator via the mirror
      separation we altered the radiative relaxation properties of the single
      chromophores and thus the FRET efficiency. We were able to achieve wavelength
      dependent enhancement factors of up to three for the spontaneous emission rate of
      the chromophores while the quenching due to the metal surfaces was nearly
      constant. We could show by confocal spectroscopy, time correlated single photon
      counting and time domain rate equation modeling that the FRET rate constant is
      not altered by our resonator. 

PMID- 25988853
TI  - Rapid, randomized development of genetically encoded FRET sensors for small
      molecules.
AB  - Imaging small molecules in living cells can be achieved with genetically encoded
      fluorescent reporters. The most common sensors emit a signal generated by Forster
      resonance energy transfer (FRET), which occurs when two fluorescent proteins that
      flank a sensor protein are moved into close proximity. This movement occurs when
      the sensor protein binds a ligand of interest. The structural requirements for
      creating this type of sensor are complex. Typically, novel sensors are developed
      by testing different linkers between the fluorescent and the binding proteins, or
      by rationally modifying the binding protein based on its three-dimensional
      structure, when the structure is available. These procedures take up to months,
      and are tedious and inefficient. Here, we developed a generally applicable method
      that starts with a ligand-binding protein of choice and generates a library with
      thousands of candidate sensors with random asymmetric truncations and mutations
      in the binding moiety. We demonstrated, with examples of sensors for glucose,
      pyruvate, and thiamine, that our method allowed identification of novel sensors
      with ample FRET responses and a wide range of affinities, within about two weeks.
      Our method does not depend on structural information, it is flexible with respect
      to the FRET pair, and it substantially enhances the speed of FRET sensor
      development. 

PMID- 25988854
TI  - Novel and recurrent mutations in WISP3 and an atypical phenotype.

PMID- 25988855
TI  - E-cadherin enhances neuregulin signaling and promotes Schwann cell myelination.
AB  - In myelinating Schwann cells, E-cadherin is a component of the adherens junctions
      that stabilize the architecture of the noncompact myelin region. In other cell
      types, E-cadherin has been considered as a signaling receptor that modulates
      intracellular signal transduction and cellular responses. To determine whether E
      cadherin plays a regulatory role during Schwann cell myelination, we investigated
      the effects of E-cadherin deletion and over-expression in Schwann cells. In vivo,
      Schwann cell-specific E-cadherin ablation results in an early myelination delay.
      In Schwann cell-dorsal root ganglia neuron co-cultures, E-cadherin deletion
      attenuates myelin formation and shortens the myelin segment length. When over
      expressed in Schwann cells, E-cadherin improves myelination on Nrg1 type III(+/-)
      neurons and induces myelination on normally non-myelinated axons of sympathetic
      neurons. The pro-myelinating effect of E-cadherin is associated with an enhanced
      Nrg1-erbB receptor signaling, including activation of the downstream Akt and Rac.
      Accordingly, in the absence of E-cadherin, Nrg1-signaling is diminished in
      Schwann cells. Our data also show that E-cadherin expression in Schwann cell is
      induced by axonal Nrg1 type III, indicating a reciprocal interaction between E
      cadherin and the Nrg1 signaling. Altogether, our data suggest a regulatory
      function of E-cadherin that modulates Nrg1 signaling and promotes Schwann cell
      myelin formation.

PMID- 25988857
TI  - Performance status as a significant prognostic predictor in patients with
      urothelial carcinoma of the bladder who underwent radical cystectomy.
AB  - OBJECTIVES: To assess the significance of performance status as a prognostic
      factor after radical cystectomy for urothelial carcinoma of the bladder. METHODS:
      The present study included 730 consecutive patients with urothelial carcinoma of
      the bladder who underwent radical cystectomy. Clinicopathological outcomes in
      these patients were analyzed focusing on the impact of performance status, which
      was assessed using the Karnofsky Performance Status scale before surgery.
      Patients were classified into groups with Karnofsky Performance Status >=90 and
      <=80. RESULTS: A total of 561 (76.8%) and 169 (23.2%) patients were judged to
      have Karnofsky Performance Status >=90 and <=80, respectively. During a mean of
      52.0 months, disease recurrence and mortality occurred in 257 (35.2%) and 249
      (34.1%) patients, respectively, and the 5-year recurrence-free and overall
      survival rates were 64.1 and 65.3%, respectively. There were significant
      differences in age, hemoglobin, albumin, estimated glomerular filtration rate,
      pathological T stage and nodal involvement between the Karnofsky Performance
      Status >=90 and <=80 groups. Multivariate analysis showed independent impacts of
      Karnofsky Performance Status, pathological T stage, nodal involvement and
      lymphovascular invasion on recurrence-free survival, as well as independent
      impacts of Karnofsky Performance Status, age, body mass index, hemoglobin,
      pathological T stage, nodal involvement and lymphovascular invasion on overall
      survival. CONCLUSIONS: The results suggest a significant association between
      impaired performance status and unfavorable prognosis in patients with urothelial
      carcinoma of the bladder undergoing radical cystectomy.

PMID- 25988858
TI  - Complement receptor of the immunoglobulin superfamily reduces murine lupus
      nephritis and cutaneous disease.
AB  - Complement activation takes place in autoimmune diseases and accounts for tissue
      inflammation. Previously, complement inhibition has been considered for the
      treatment of SLE. Complement receptor of the immunoglobulin superfamily (CRIg) is
      a selective inhibitor of the alternative pathway of complement and a soluble form
      reverses established inflammation and bone destruction in experimental autoimmune
      arthritis. We asked whether specific inhibition of the alternative pathway could
      inhibit autoimmunity and/or organ damage in lupus-prone mice. Accordingly, we
      treated lupus-prone MRL/lpr mice with a soluble form of CRIg (CRIg-Fc) and we
      found that it significantly diminished skin lesions, proteinuria and pyuria, and
      kidney pathology. Interestingly, serum levels of anti-DNA antibodies were not
      affected despite the fact that serum complement 3 (C3) levels increased
      significantly. Immunofluorescent staining of kidney tissues revealed a reduction
      in staining intensity for C3, IgG, and the macrophage marker Mac-2. Thus our data
      show that inhibition of the alternative pathway of complement controls skin and
      kidney inflammation even in the absence of an effect on the production of
      autoantibodies. We propose that CRIg should be considered for clinical trials in
      patients with systemic lupus erythematosus. 

PMID- 25988856
TI  - New insights into heterogeneity of peritoneal B-1a cells.
AB  - Peritoneal B-1a cells are characterized by their expression of CD5 and enrichment
      for germline-encoded IgM B cell receptors. Early studies showing expression of a
      diverse array of VDJ sequences among purified B-1a cells provided a molecular
      basis for understanding the heterogeneity of the B-1a cell repertoire. Antigen
      driven positive selection and the identification of B-1a specific progenitors
      suggest multiple origins of B-1a cells. The introduction of new markers such as
      PD-L2, CD25, CD73, and PC1 (plasma cell alloantigen 1, also known as
      ectonucleotide phosphodiesterase/pyrophosphatase 1) further helped to identify
      phenotypically and functionally distinct B-1a subsets. Among many B-1a subsets
      defined by these new markers, PC1 is unique in that it subdivides B-1a cells into
      PC1(hi) and PC1(lo) subpopulations with distinct functions, such as production of
      natural IgM and gut IgA, response to the pneumococcal antigen PPS-3, secretion of
      interleukin-10, and support for T helper 1 (TH 1) cell differentiation. RNA
      sequencing of these subsets revealed differential expression of genes involved in
      cellular movement and immune cell trafficking. We will discuss these new insights
      underlying the heterogeneous nature of the B-1a cell repertoire. 

PMID- 25988859
TI  - Control of intestinal homeostasis through crosstalk between natural killer T
      cells and the intestinal microbiota.
AB  - The human host and the intestinal microbiota co-exist in a mutually beneficial
      relationship, which contributes to host and microbial metabolism as well as
      maturation of the host's immune system, among many other pathways (Tremaroli and
      Backhed, 2012; Hooper et al., 2012). At mucosal surfaces, and particularly in the
      intestine, the commensal microbiota provides 'colonization resistance' to
      invading pathogens and maintains homeostasis through microbial regulation of
      mucosal innate and adaptive immunity (Renz et al., 2012). Recent evidence
      suggests that natural killer T cells (NKT cells), a subgroup of lipid-reactive T
      cells, play central roles in bidirectional interactions between the host and the
      commensal microbiota, which govern intestinal homeostasis and prevent
      inflammation. Here, we provide a brief overview of recently identified pathways
      of commensal microbial regulation of NKT cells, discuss feedback mechanisms of
      NKT cell-dependent control of microbial colonization and composition, and
      highlight the critical role of host-microbial cross-talk for prevention of NKT
      cell-dependent mucosal inflammation. 

PMID- 25988860
TI  - New developments providing mechanistic insight into the impact of the microbiota
      on allergic disease.
AB  - The increase in allergic diseases over the past several decades is correlated
      with changes in the composition and diversity of the intestinal microbiota.
      Microbial-derived signals are critical for instructing the developing immune
      system and conversely, immune regulation can impact the microbiota. Perturbations
      in the microbiota composition may be especially important during early-life when
      the immune system is still developing, resulting in a critical window of
      opportunity for instructing the immune system. This review highlights recent
      studies investigating the role of the microbiome in susceptibility or development
      of allergic diseases with a focus on animal models that provide insight into the
      mechanisms and pathways involved. Identification of a causal link between reduced
      microbial diversity or altered microbial composition and increased susceptibility
      to immune-mediated diseases will hopefully pave the way for better preventive
      therapies. 

PMID- 25988863
TI  - EpCAM-Antibody-Labeled Noncytotoxic Polymer Vesicles for Cancer Stem Cells
      Targeted Delivery of Anticancer Drug and siRNA.
AB  - Cancer stem cells (CSCs) have the capability to initiate tumor, to sustain tumor
      growth, to maintain the heterogeneity of tumor, and are closely linked to the
      failure of chemotherapy due to their self-renewal and multilineage
      differentiation capability with an innate resistance to cytotoxic agents. Herein,
      we designed and synthesized a novel anti-EpCAM (epithelial cell adhesion
      molecule)-monoclonal-antibody-labeled CSCs-targeting, noncytotoxic and pH
      sensitive block copolymer vesicle as a nanocarrier of anticancer drug and siRNA
      (to overcome CSCs drug resistance by silencing the expression of oncogenes). This
      vesicle shows high delivery efficacy of both anticancer drug doxorubicin
      hydrochloride (DOX.HCl) and siRNA to the CSCs because it is labeled by the
      monoclonal antibodies to the CSCs-surface-specific marker. Compared to non-CSCs
      targeting vesicles, the DOX.HCl or siRNA loaded CSCs-targeting vesicles exhibited
      much better CSCs killing and tumor growth inhibition capabilities with lower
      toxicity to normal cells (IC50,DOX decreased by 80%), demonstrating promising
      potential applications in nanomedicine. 

PMID- 25988861
TI  - Bone marrow transcriptome and epigenome profiles of equine common variable
      immunodeficiency patients unveil block of B lymphocyte differentiation.
AB  - Common variable immunodeficiency (CVID) is a late-onset humoral deficiency
      characterized by B lymphocyte dysfunction or loss, decreased immunoglobulin
      production, and recurrent bacterial infections. CVID is the most frequent human
      primary immunodeficiency but still presents challenges in the understanding of
      its etiology and treatment. CVID in equine patients manifests with a natural
      impairment of B lymphocyte differentiation, and is a unique model to identify
      genetic and epigenetic mechanisms of disease. Bone marrow transcriptome analyses
      revealed decreased expression of genes indicative of the pro-B cell
      differentiation stage, importantly PAX5 (p<=0.023). We hypothesized that aberrant
      epigenetic regulation caused PAX5 gene silencing, resulting in the late-onset and
      non-familial manifestation of CVID. A significant increase in PAX5 enhancer
      region methylation was identified in equine CVID patients by genome-wide reduced
      representation bisulfite sequencing and bisulfite PCR sequencing (p=0.000). Thus,
      we demonstrate that integrating transcriptomics and epigenetics in CVID
      enlightens potential mechanisms of dysfunctional B lymphopoiesis or function. 

PMID- 25988862
TI  - Novel CFI mutation in a patient with leukocytoclastic vasculitis may redefine the
      clinical spectrum of Complement Factor I deficiency.
AB  - Factor I is an important regulator of the complement system. Lack of Factor I
      causes uncontrolled activation of the complement system leading to consumption of
      C3. Complete deficiency of Factor I is a rare condition and only around 40 cases
      has been reported in the literature. The clinical presentation of Factor I
      deficiency varies and includes severe recurrent bacterial infections,
      glomerulonephritis and autoimmune diseases. The patient, a 28-years old woman
      with consanguineous parents, presented with recurrent leukocytoclastic vasculitis
      in the lower extremities with no associated systemic involvement, and without
      increased infection tendency. Initial testing showed low C3 concentration and a
      detailed complement evaluation absence of complement Factor I. Sequencing
      revealed a homozygous missense mutation in exon 2 of the CFI gene (SCV000221312).
      Even though the clinical symptoms of CFI mutations vary among patients sole
      association with leukocytoclastic vasculitis redefines the clinical spectrum of
      complete Factor I deficiency. 

PMID- 25988865
TI  - Influence of antihypertensive therapy on cerebral perfusion in patients with
      metabolic syndrome: relationship with cognitive function and 24-h arterial blood
      pressure monitoring.
AB  - AIMS: To investigate the regional cerebral blood flow, cognitive function, and
      parameters of 24-h arterial blood pressure monitoring in patients with metabolic
      syndrome before and after combination antihypertensive therapy. METHODS: The
      study involved 54 patients with metabolic syndrome (MetS) investigated by brain
      single-photon emission computed tomography, 24-h blood pressure monitoring
      (ABPM), and comprehensive neuropsychological testing before and after 24 weeks of
      combination antihypertensive therapy. RESULTS: Patients with metabolic syndrome
      had significantly poorer regional cerebral blood flow compared with control
      group: by 7% (P = 0.003) in right anterior parietal cortex, by 6% (P = 0.028) in
      left anterior parietal cortex, by 8% (P = 0.007) in right superior frontal lobe,
      and by 10% (P = 0.00002) and 7% (P = 0.006) in right and left temporal brain
      regions, correspondingly. The results of neuropsychological testing showed 11%
      decrease in mentation (P = 0.002), and 19% (P = 0.011) and 20% (P = 0.009)
      decrease in immediate verbal and visual memory in patients with MetS as compared
      with control group. Relationships between the indices of ABPM, cerebral
      perfusion, and cognitive function were found. Data showed an improvement of
      regional cerebral blood flow, ABPM parameters, and indicators of cognitive
      functions after 6 months of antihypertensive therapy in patients with MetS.
      CONCLUSION: The study showed the presence of diffuse disturbances in cerebral
      perfusion is associated with cognitive disorders in patients with metabolic
      syndrome. Combination antihypertensive treatment exerts beneficial effects on the
      24-h blood pressure profile, increases cerebral blood flow, and improves
      cognitive function in patients with MetS.

PMID- 25988864
TI  - IL-9 inhibits HTB-72 melanoma cell growth through upregulation of p21 and TRAIL.
AB  - BACKGROUND: IL-9 is a pleiotropic cytokine produced mainly by Th9 cells. IL-9 may
      have an anti-proliferative role in murine melanoma, however, its effect on human
      melanoma is unknown. METHODS: We examined the effects of IL-9 on proliferation
      and apoptosis in four human melanoma cell lines, HTB-65, HTB-72, CRL-11147, and
      SK-Mel-5. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL
      staining and caspase-3 activity assay were used to assess proliferation and
      apoptosis, as appropriate. RESULTS: We found that IL-9 decreased the percentage
      of colonies of HTB-72 and SK-Mel-5 cells but not that of HTB-65 or CRL-11147
      cells. PCNA mRNA, PCNA+ cells, PCNA staining intensity, and the OD value of HTB
      72 melanoma cells were consistently decreased in the present of IL-9. IL-9 also
      increased TUNEL+ cells and the relative caspase-3 activity in HTB-72 melanoma
      cells. We further investigated the possible molecular mechanisms using RT-PCR and
      immunohistochemical staining. The anti-proliferative effect of IL-9 on HTB-72
      cells correlated with higher expression of anti-proliferative molecule p21. Its
      pro-apoptotic effect on HTB-72 cells correlated with higher expression of the pro
      apoptotic molecule TRAIL. CONCLUSIONS: IL-9 inhibits melanoma HTB-72 cell growth
      by upregulation of p21 and TRAIL. Understanding the interactions between IL-9 and
      melanoma may help direct strategies for cytokine-based immunotherapy development.

PMID- 25988866
TI  - A comparison of patterns of spontaneous adverse drug reaction reporting with St.
      John's Wort and fluoxetine during the period 2000-2013.
AB  - Herbal medicines are perceived to be safe by the general public and medical
      practitioners, despite abundant evidence from clinical trials and case reports
      that show herbal preparations can have significant adverse effects. The overall
      impact of adverse events to herbal medicines in Australia is currently unknown.
      Post marketing surveillance of medications through spontaneous adverse drug
      reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way
      to estimate this risk. The patterns of spontaneously reported ADRs provide
      insight to herbal dangers, especially when compared with patterns of a
      mechanistically similar conventional drug. The study compared the pattern of
      spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common
      herbal treatment for depression which contains selective serotonin reuptake
      inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI
      antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St.
      John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The
      demographic information, types of interaction, severity of the ADR, and the body
      systems affected (using the Anatomical Therapeutic Chemical classification
      system) were recorded for individual ADR cases. The majority of spontaneously
      reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26
      50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and
      fluoxetine have a similar profile, with the majority of cases affecting the
      central nervous system (45.2%, 61.7%). This result demonstrates that herbal
      preparations can result in ADRs similar to those of prescription medications.

PMID- 25988867
TI  - Copper-Catalyzed Coupling Cyclization of gem-Difluoroalkenes with Activated
      Methylene Carbonyl Compounds: Facile Domino Access to Polysubstituted Furans.
AB  - A novel and efficient CuI-catalyzed synthesis of 2,3,5-trisubstituted furans was
      developed via coupling cyclization of gem-difluoroalkenes with active methylene
      carbonyl compounds such as 1,3-dicarbonyl compounds, acetoacetonitrile, and
      phenylsulfonylacetone with the assistance of a base. Commercial availability of
      substrates or reagents, good to high isolated yields, and excellent functional
      group compatibility make this transformation a powerful tool for the synthesis of
      various furans. A plausible mechanism involving the allenyl ketone is suggested. 

PMID- 25988868
TI  - Comparing Fast Pressure Jump and Temperature Jump Protein Folding Experiments and
      Simulations.
AB  - The unimolecular folding reaction of small proteins is now amenable to a very
      direct mechanistic comparison between experiment and simulation. We present such
      a comparison of microsecond pressure and temperature jump refolding kinetics of
      the engineered WW domain FiP35, a model system for beta-sheet folding. Both
      perturbations produce experimentally a faster and a slower kinetic phase, and the
      "slow" microsecond phase is activated. The fast phase shows differences between
      perturbation methods and is closer to the downhill limit by temperature jump, but
      closer to the transiently populated intermediate limit by pressure jump. These
      observations make more demands on simulations of the folding process than just a
      rough comparison of time scales. To complement experiments, we carried out
      several pressure jump and temperature jump all-atom molecular dynamics
      trajectories in explicit solvent, where FiP35 folded in five of the six
      simulations. We analyzed our pressure jump simulations by kinetic modeling and
      found that the pressure jump experiments and MD simulations are most consistent
      with a 4-state kinetic mechanism. Together, our experimental and computational
      data highlight FiP35's position at the boundary where activated intermediates and
      downhill folding meet, and we show that this model protein is an excellent
      candidate for further pressure jump molecular dynamics studies to compare
      experiment and modeling at the folding mechanism level. 

PMID- 25988869
TI  - Routine filtration of hematopoietic stem cell products: the time has arrived.
AB  - BACKGROUND: Most blood products are infused at the time of transfusion through a
      standard blood filter, designed to capture macroaggregates and cellular debris
      that might be harmful to the patient if infused. Hematopoietic stem cell products
      are not universally filtered, likely due to concern about loss of viable stem
      cells in the filtration process. STUDY DESIGN AND METHODS: We conducted a two
      phase study to better understand the safety of routine filtration. First, surplus
      cryopreserved stem cell products were thawed and filtered, with markers of
      viability and potency measured. Second, routine filtration was implemented as
      part of routine practice at our center, and date of neutrophil and platelet (PLT)
      recovery was compared to historical controls. RESULTS: In the first phase, there
      was no difference seen in any markers of viability or potency for products after
      routine filtration. Based on those results, routine filtration was implemented.
      There was no difference in neutrophil or PLT engraftment. Thus, in this study,
      routine filtration did not impact the number of viable stem cells and did not
      delay engraftment. CONCLUSION: Given the very real harm posed by infusion of
      macroaggregates and cellular debris, and no clear disadvantage to filtration,
      routine filtration of stem cell products should be considered the standard of
      care.

PMID- 25988870
TI  - Determining the leaf emissivity of three crops by infrared thermometry.
AB  - Plant temperature can provide important physiological information for crop
      management. Non-contact measurement with an infrared thermometer is useful for
      detecting leaf temperatures. In this study, a novel technique was developed to
      measure leaf emissivity using an infrared thermometer with an infrared sensor and
      a thermocouple wire. The measured values were transformed into true temperatures
      by calibration equations to improve the measurement accuracy. The relationship
      between two kinds of measurement temperatures and setting emissivities was
      derived as a model for calculating of true emissivity. The emissivities of leaves
      of three crops were calculated by the mathematical equation developed in this
      study. The mean emissivities were 0.9809, 0.9783, 0.981 and 0.9848 for
      Phalaenopsis mature and new leaves and Paphiopedilum and Malabar chestnut leaves,
      respectively. Emissivity differed significantly between leaves of Malabar
      chestnut and the two orchids. The range of emissivities determined in this study
      was similar to that in the literature. The precision of the measurement is
      acceptable. The method developed in this study is a real-time, in situ technique
      and could be used for agricultural and forestry plants. 

PMID- 25988871
TI  - Intelligent detection of cracks in metallic surfaces using a waveguide sensor
      loaded with metamaterial elements.
AB  - This work presents a real life experiment of implementing an artificial
      intelligence model for detecting sub-millimeter cracks in metallic surfaces on a
      dataset obtained from a waveguide sensor loaded with metamaterial elements. Crack
      detection using microwave sensors is typically based on human observation of
      change in the sensor's signal (pattern) depicted on a high-resolution screen of
      the test equipment. However, as demonstrated in this work, implementing
      artificial intelligence to classify cracked from non-cracked surfaces has
      appreciable impact in terms of sensing sensitivity, cost, and automation.
      Furthermore, applying artificial intelligence for post-processing data collected
      from microwave sensors is a cornerstone for handheld test equipment that can
      outperform rack equipment with large screens and sophisticated plotting features.
      The proposed method was tested on a metallic plate with different cracks and the
      obtained experimental results showed good crack classification accuracy rates. 

PMID- 25988872
TI  - Dominant tree species are at risk from exaggerated drought under climate change.
AB  - Predicting the consequences of climate change on forest systems is difficult
      because trees may display species-specific responses to exaggerated droughts that
      may not be reflected by the climatic envelope of their geographic range.
      Furthermore, few studies have examined the postdrought recovery potential of
      drought-susceptible tree species. This study develops a robust ranking of the
      drought susceptibility of 21 tree species based on their mortality after two
      droughts (1990s and 2000s) in the savanna of north-eastern Australia. Drought
      induced mortality was positively related to species dominance, negatively related
      to the ratio of postdrought seedlings to adults and had no relationship to the
      magnitude of extreme drought within the species current geographic ranges. These
      results suggest that predicting the consequences of exaggerated drought on
      species' geographic ranges is difficult, but that dominant species like
      Eucalyptus with relatively slow rates of population recovery and dispersal are
      the most susceptible. The implications for savanna ecosystems are lower tree
      densities and basal area. 

PMID- 25988874
TI  - Metformin inhibits age-related centrosome amplification in Drosophila midgut stem
      cells through AKT/TOR pathway.
AB  - We delineated the mechanism regulating the inhibition of centrosome amplification
      by metformin in Drosophila intestinal stem cells (ISCs). Age-related changes in
      tissue-resident stem cells may be closely associated with tissue aging and age
      related diseases, such as cancer. Centrosome amplification is a hallmark of
      cancers. Our recent work showed that Drosophila ISCs are an excellent model for
      stem cell studies evaluating age-related increase in centrosome amplification.
      Here, we showed that metformin, a recognized anti-cancer drug, inhibits age- and
      oxidative stress-induced centrosome amplification in ISCs. Furthermore, we
      revealed that this effect is mediated via down-regulation of AKT/target of
      rapamycin (TOR) activity, suggesting that metformin prevents centrosome
      amplification by inhibiting the TOR signaling pathway. Additionally, AKT/TOR
      signaling hyperactivation and metformin treatment indicated a strong correlation
      between DNA damage accumulation and centrosome amplification in ISCs, suggesting
      that DNA damage might mediate centrosome amplification. Our study reveals the
      beneficial and protective effects of metformin on centrosome amplification via
      AKT/TOR signaling modulation. We identified a new target for the inhibition of
      age- and oxidative stress-induced centrosome amplification. We propose that the
      Drosophila ISCs may be an excellent model system for in vivo studies evaluating
      the effects of anti-cancer drugs on tissue-resident stem cell aging. 

PMID- 25988873
TI  - Venous thrombosis and cancer: from mouse models to clinical trials.
AB  - Cancer patients have a ~4 fold increased risk of venous thromboembolism (VTE)
      compared with the general population and this is associated with significant
      morbidity and mortality. This review summarizes our current knowledge of VTE and
      cancer, from mouse models to clinical studies. Notably, the risk of VTE varies
      depending on the type and stage of cancer. For instance, pancreatic and brain
      cancer patients have a higher risk of VTE than breast and prostate cancer
      patients. Moreover, patients with metastatic disease have a higher risk than
      those with localized tumors. Tumor-derived procoagulant factors and growth
      factors may directly and indirectly enhance VTE. For example, increased levels of
      circulating tumor-derived, tissue factor-positive microvesicles may trigger VTE.
      In a mouse model of ovarian cancer, tumor-derived IL-6 and hepatic thrombopoietin
      have been linked to increased platelet production and thrombosis. In addition,
      mouse models of mammary and lung cancer showed that tumor-derived granulocyte
      colony-stimulating factor causes neutrophilia and activation of neutrophils.
      Activated neutrophils can release neutrophil extracellular traps (NETs) that
      enhance thrombosis. Cell-free DNA in the blood derived from cancer cells, NETs
      and treatment with cytotoxic drugs can activate the clotting cascade. These
      studies suggest that there are multiple mechanisms for VTE in patients with
      different types of cancer. Preventing and treating VTE in cancer patients is
      challenging; the current recommendations are to use low-molecular-weight heparin.
      Understanding the underlying mechanisms may allow the development of new
      therapies to safely prevent VTE in cancer patients. 

PMID- 25988876
TI  - Childhood parental mental illness: living with fear and mistrust.
AB  - This paper presents one major theme of findings from a doctorate study. The study
      used a narrative enquiry approach, to gather parenting narratives of adult
      children of parents with mental illness. A Partnership Model for a Reflexive
      Narrative for Participant and Researcher (Partnership Model) was used to invite
      participants into the study, while encouraging a space for reflection for both
      the adult children and researcher. In total, 13 adult children participants
      constructed their narratives of living with childhood parental mental illness,
      alongside their current parenting role. Their stories reflected childhood
      experiences of fear and emergence of mistrust of others, particularly their
      parent with mental illness. For some participants, fear and mistrust continued
      into adulthood. Many adult children reported their childhood experiences of
      feeling lonely and isolated. They felt unable to disclose their experiences of
      parental mental illness to others. In addition, participants were unable to
      access information about their parent's condition, leaving them feeling
      unprepared and unskilled, despite their childhood desire to help their parent.
      This furthermore, compounded their sense of fear and isolation. Early
      identification of children and families experiencing mental illness is important
      to facilitate dialogue, psychoeducation and support. Social and health
      professionals have an important opportunity to enhance the social integration and
      support for families experiencing parental mental illness, to reduce long
      standing fear, isolation and mistrust. 

PMID- 25988875
TI  - Punitive preferences, monetary incentives and tacit coordination in the
      punishment of defectors promote cooperation in humans.
AB  - Peer-punishment is effective in promoting cooperation, but the costs associated
      with punishing defectors often exceed the benefits for the group. It has been
      argued that centralized punishment institutions can overcome the detrimental
      effects of peer-punishment. However, this argument presupposes the existence of a
      legitimate authority and leaves an unresolved gap in the transition from peer
      punishment to centralized punishment. Here we show that the origins of
      centralized punishment could lie in individuals' distinct ability to punish
      defectors. In our laboratory experiment, we vary the structure of the punishment
      situation to disentangle the effects of punitive preferences, monetary
      incentives, and individual punishment costs on the punishment of defectors. We
      find that actors tacitly coordinate on the strongest group member to punish
      defectors, even if the strongest individual incurs a net loss from punishment.
      Such coordination leads to a more effective and more efficient provision of a
      cooperative environment than we observe in groups of all equals. Our results show
      that even an arbitrary assignment of an individual to a focal position in the
      social hierarchy can trigger the endogenous emergence of more centralized forms
      of punishment. 

PMID- 25988878
TI  - Light and color in a void: The analysis of a special needs child.
AB  - This clinical report comes from the five year, four day a week analysis of a male
      child. What is special is that this treatment is of a child with marked mental
      retardation. I have retained this nomenclature because that is how Ricardo's
      parents described his mental capacity. What they meant was that he was greatly
      impaired in his cognition and this could be seen in Ricardo's severe cognitive,
      social, behavioral, and relational improprieties. I have privileged the function
      of psychoanalytic understanding and the role of transference to bring about
      modifications in this child's internal world. And I have considered the patient's
      psychotic mental state to be in need of psychoanalytic treatment not withstanding
      his psychosis's connection to his cognitive handicap. I have also added
      information I have received after the analysis, information that demonstrates
      continued integration coming from the analytic process. Owing to Ricardo's
      limited mental capacities, this article advances clinical information that is not
      often found in analyses of children. There are possibly many other children like
      him who nonetheless would benefit from dynamic psychoanalytic understanding. On
      the other hand, I shall not discuss this matter theoretically, even though some
      theoretic considerations are necessary. Clinical practice and the transferential
      relation are this report's principal material. 

PMID- 25988877
TI  - The cost-effectiveness of drug therapies to treat secondary hyperparathyroidism
      in renal failure: a focus on evidence regarding paricalcitol and cinacalcet.
AB  - The present review aims to assess the state-of-the-art regarding cost
      effectiveness of therapy for secondary hyperparathyroidism in order to identify
      the best treatment and review methodological issues. PubMed and the Cochrane
      Library were searched to identify papers performing comparative analysis of costs
      and effects of treatment for secondary hyperparathyroidism in adult patients.
      Among the 66 papers identified, only 10 were included in the analysis. Treatment
      strategies evaluated in the selected papers were: cinacalcet in addition to
      vitamin D and phosphate binders versus vitamin D and phosphate binders only
      (seven papers), paricalcitol versus non-selective vitamin D (two papers), early
      and late introduction of cinacalcet in addition to vitamin D and phosphate
      binders (one paper) and paricalcitol versus cinacalcet (one paper). The high
      degree of heterogeneity among alternative treatments and methodological limits
      related to cost items considered, resource valuation methods and so on, make it
      unfeasible to reach a definite conclusion regarding cost-effectiveness but allow
      for future research opportunities. 

PMID- 25988879
TI  - Cardiac Nitric Oxide Synthases and Na+/K+-ATPase in the Rat Model of Polycystic
      Ovary Syndrome Induced by Dihydrotestosterone.
AB  - Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for
      regular functioning of the heart. Since both enzymes are under insulin and
      androgen regulation and since insulin action and androgen level were disturbed in
      polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO)
      production and sodium/potassium transport would be deteriorated in PCOS. To test
      our hypothesis we introduced animal model of PCOS based on dihydrotestosterone
      (DHT) treatment of female Wistar rats and analyzed protein expression,
      phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible
      NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results
      indicate that DHT treatment significantly decreased cardiac eNOS protein level
      and activating phosphorylation at serine 1,177, while inhibitory phosphorylation
      at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein
      level in the heart of DHT-treated rats was significantly elevated. Furthermore,
      cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma
      membrane content, were decreased in rats with PCOS. In line with this, alpha 2
      subunit protein level in fraction of plasma membranes was also significantly
      below control level. In conclusion, DHT treatment impaired effectiveness of NOSs
      and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO
      production and sodium/potassium transport in the cardiac contraction and blood
      flow regulation, it implicates strong consequences of PCOS for heart functioning.

PMID- 25988880
TI  - Glucose- and Triglyceride-lowering Dietary Penta-O-galloyl-alpha-D-Glucose
      Reduces Expression of PPARgamma and C/EBPalpha, Induces p21-Mediated G1 Phase
      Cell Cycle Arrest, and Inhibits Adipogenesis in 3T3-L1 Preadipocytes.
AB  - Plant polyphenols, such as hydrolysable tannins, are present in the human diet
      and known to exhibit anti-diabetic and anti-obesity activity. We previously
      reported that the representative hydrolysable tannin compound alpha-penta-galloyl
      glucose (alpha-PGG) is a small molecule insulin mimetic that, like insulin, binds
      to insulin receptor (IR) and activates the IR-Akt-GLUT4 signaling pathway to
      trigger glucose transport and reduce blood glucose levels in db/db and ob/ob
      diabetic mice. However, its effects on adipogenesis and lipid metabolism were not
      known. In this study, high fat diet (HFD)-induced diabetic and obese mice were
      treated with alpha-PGG to determine its effects on blood glucose and
      triglycerides. 3T3-L1 preadipocytes were used as a cell model for identifying the
      anti-adipogenic activity of alpha-PGG at molecular and cellular levels as a first
      step in elucidating the mechanism of action of the compound. In vivo, oral
      administration of alpha-PGG significantly reduced levels of blood glucose,
      triglyceride, and insulin in HFD-induced diabetic/obese mice (P<0.05). In vitro,
      alpha-PGG inhibited the differentiation of 3T3-L1 preadipocytes into mature
      adipocytes. alpha-PGG suppressed the expression of positive adipogenic factors
      PPARgamma C/EBPalpha and mTOR and augmented the negative adipogenic factor Pref
      1. Furthermore, alpha-PGG induced upregulation of p21 and G1 phase cell cycle
      arrest. In contrast, adipogenic signaling pathways mediated by insulin, the cAMP
      response element binding protein (CREB) and glucocorticoid receptor (GR), were
      not inhibited. RNAi knockdown of p21 led to a 4-fold increase in triglyceride
      level in 3T3-L1 preadipocytes treated with MDI and alpha-PGG compared to regular
      preadipocytes. These results indicate, for the first time, that alpha-PGG is
      blood triglyceride- and glucose-lowering in HFD-induced obese and diabetic mice.
      It selectively inhibited some but not all major adipogenic pathways as well as
      the mTOR-p21-mediated cell cycle regulatory pathway. It is very likely that these
      apparently diverse but coordinated activities together inhibited adipogenesis.
      These results expand our knowledge on how PGG works in adipocytes and further
      confirm that alpha-PGG functions as an orally-deliverable natural insulin mimetic
      with adipogenetic modulatory functions. 

PMID- 25988881
TI  - Comparative Efficacy of Four Treatments in Patients with Graves' Disease: a
      Network Meta-analysis.
AB  - BACKGROUND: The question of which treatment should be preferred for the treatment
      of Graves' disease is debatable, and pairwise meta-analyses could not obtain
      hierarchies of these treatments. Our intention was to integrate the evidence to
      provide hierarchies of the comparative efficacy of 4 treatments (radioiodine,
      radioiodine+prednisone, antithyroid drugs and surgery). METHODS: We conducted a
      Bayesian-framework network meta-analysis of randomized controlled trials (RCTs)
      to compare 4 treatments in patients with Graves' disease. The eligible RCTs were
      identified by searching Amed, the British Nursing Index, Embase, PubMed, the
      Cochrane Central Register of Controlled Trials (CENTRAL), Google scholar, SIGLE,
      the National Technical Information Service, the National Research Register (UK)
      and the Current Controlled Trials databases. The data for 2 outcomes (e.g.,
      ophthalmopathy and recurrence) were independently extracted by 2 authors.
      RESULTS: A total of 4 RCTs were ultimately included. Radioiodine+prednisone
      therapy showed statistical significance in reducing the incidence of new or
      deteriorative ophthalmopathy comparing with the other 3 therapies. Compared with
      radioiodine, therapy with antithyroid drugs therapy as well as surgery
      significantly decreased the incidence of new or deteriorative ophthalmopathy.
      Radioiodine therapy significantly reduced the rate of recurrence when compared to
      therapy with antithyroid drugs or surgery. For decreasing the incidence of new or
      deteriorative ophthalmopathy, the 4 treatments were ranked as follows:
      radioiodine+prednisone therapy, therapy with antithyroid drugs, surgery and
      radioiodine therapy. For reducing the rate of recurrence, 3 treatments were
      ranked as follows: radioiodine therapy, therapy with antithyroid drugs and
      surgery. CONCLUSIONS: Radioiodine+prednisone therapy might have the least
      probability of leading to an exacerbation or new appearance of ophthalmopathy,
      and radioiodine therapy might have the least probability of causing a recurrence.

PMID- 25988882
TI  - Comparison of lacosamide concentrations in cerebrospinal fluid and serum in
      patients with epilepsy.
AB  - OBJECTIVE: This study was carried out to estimate the exposure of the central
      nervous system (CNS) to the antiepileptic drug (AED) lacosamide, under steady
      state conditions, in patients with epilepsy who take oral lacosamide alongside up
      to three other AEDs. METHODS: Twenty-seven serum and cerebral spinal fluid (CSF)
      samples were collected from 21 patients receiving lacosamide for the treatment of
      epilepsy (50-600 mg/day over two or three doses). This included 23 time-matched
      pairs of serum and CSF samples from 19 patients. The concentration of lacosamide
      in each sample was determined using high-performance liquid chromatography tandem
      mass spectrometry (HPLC-MS/MS). Linear regression was used to characterize the
      relationship between the CSF-to-serum ratio of lacosamide concentration and the
      time since dosing, the daily lacosamide dose, or the daily dose normalized by
      volume of distribution (Vd , approximated to total body water), and between the
      drug concentrations in each compartment (CSF vs. serum). RESULTS: Concentrations
      of lacosamide in CSF (mean +/- standard deviation [SD] 7.37 +/- 3.73 MUg/ml,
      range 1.24-14.95, n = 27) and serum (mean +/- SD 8.16 +/- 3.82 MUg/ml, range 2.29
      15.45, n = 27) samples showed a good correlation over the dose range
      investigated. The mean CSF-to-serum ratio of lacosamide concentrations was 0.897
      +/- 0.193 (range 0.492-1.254, n = 23 time-matched pairs) and was independent of
      lacosamide dose. SIGNIFICANCE: Drug concentrations in the CSF are often used to
      indicate those in the brain interstitial fluid. In patients with epilepsy who
      follow a stable oral AED dosing regimen, lacosamide concentration in CSF is
      approximately 85% of that found in serum, suggesting that serum may be a valuable
      indicator of lacosamide concentration in the CNS.

PMID- 25988884
TI  - Prospective assessment of health-related quality of life in men with late-onset
      hypogonadism who received testosterone replacement therapy.
AB  - The objective of this study was to characterise the status of health-related
      quality of life (HRQOL) in Japanese men with late-onset hypogonadism (LOH)
      treated with testosterone replacement therapy (TRT). HRQOL in 69 consecutive
      Japanese men with LOH undergoing TRT for at least 6 months was prospectively
      evaluated before and 6 months after the initiation of TRT using the Medical
      Outcomes Study 8-Item Short-Form Health Survey (SF-8). All eight-scale scores
      except for bodily pain (BP) in the 69 patients at 6 months after the introduction
      of TRT significantly improved compared with those before TRT; however, all scale
      scores except for BP in the 69 patients were significantly inferior to those in
      age-matched Japanese controls irrespective of the timing of SF-8. Multivariate
      analyses of several parameters revealed that both age and Aging Male Symptom
      (AMS) score had an independent impact on mental health (MH), despite the lack of
      an independent association between any score and the remaining factors examined.
      TRT appeared to significantly improve the status of HRQOL in men with LOH;
      however, even after the introduction of TRT, HRQOL associated with MH remained
      significantly impaired in elderly men and/or those with a high AMS score. 

PMID- 25988885
TI  - A formidable challenge.

PMID- 25988886
TI  - Intrinsic host restrictions to HIV-1 and mechanisms of viral escape.
AB  - To replicate in their hosts, viruses have to navigate the complexities of the
      mammalian cell, co-opting mechanisms of cellular physiology while defeating
      restriction factors that are dedicated to halting their progression. Primate
      lentiviruses devote a relatively large portion of their coding capacity to
      counteracting restriction factors by encoding accessory proteins dedicated to
      neutralizing the antiviral function of these intracellular inhibitors. Research
      into the roles of the accessory proteins has revealed the existence of previously
      undetected intrinsic defenses, provided insight into the evolution of primate
      lentiviruses as they adapt to new species and uncovered new targets for the
      development of therapeutics. This Review discusses the biology of the restriction
      factors APOBEC3, SAMHD1 and tetherin and the viral accessory proteins that
      counteract them. 

PMID- 25988887
TI  - Innate immunity against HIV-1 infection.
AB  - During acute HIV-1 infection, viral pathogen-associated molecular patterns are
      recognized by pathogen-recognition receptors (PRRs) of infected cells, which
      triggers a signaling cascade that initiates innate intracellular antiviral
      defenses aimed at restricting the replication and spread of the virus. This cell
      intrinsic response propagates outward via the action of secreted factors such as
      cytokines and chemokines that activate innate immune cells and attract them to
      the site of infection and to local lymphatic tissue. Antiviral innate effector
      cells can subsequently contribute to the control of viremia and modulate the
      quality of the adaptive immune response to HIV-1. The concerted actions of PRR
      signaling, specific viral-restriction factors, innate immune cells, innate
      adaptive immune crosstalk and viral evasion strategies determine the outcome of
      HIV-1 infection and immune responses. 

PMID- 25988888
TI  - Success and failure of the cellular immune response against HIV-1.
AB  - The cellular immune response to HIV-1 has now been studied in extraordinary
      detail. A very large body of data provides the most likely reasons that the HIV
      specific cellular immune response succeeds in a small number of people but fails
      in most. Understanding the success and failure of the HIV-specific cellular
      immune response has implications that extend not only to immunotherapies and
      vaccines for HIV-1 but also to the cellular immune response in other disease
      states. This Review focuses on the mechanisms that are most likely responsible
      for durable and potent immunologic control of HIV-1. Although we now have a
      detailed picture of the cellular immune responses to HIV-1, important questions
      remain regarding the nature of these responses and how they arise. 

PMID- 25988897
TI  - Paula Pitha-Rowe 1937-2015.

PMID- 25988898
TI  - TET1: an epigenetic guardian of lymphomagenesis.

PMID- 25988890
TI  - The impact of host genetic variation on infection with HIV-1.
AB  - The outcome after infection with the human immunodeficiency virus type 1 (HIV-1)
      is a complex phenotype determined by interactions among the pathogen, the human
      host and the surrounding environment. An impact of host genetic variation on HIV
      1 susceptibility was identified early in the pandemic, with a major role
      attributed to the genes encoding class I human leukocyte antigens (HLA) and the
      chemokine receptor CCR5. Studies using genome-wide data sets have underscored the
      strength of these associations relative to variants located throughout the rest
      of the genome. However, the extent to which additional polymorphisms influence
      HIV-1 disease progression, and how much of the variability in outcome can be
      attributed to host genetics, remain largely unclear. Here we discuss findings
      concerning the functional impact of associated variants, outline methods for
      quantifying the host genetic component and examine how available genome-wide data
      sets may be leveraged to discover gene variants that affect the outcome of HIV-1
      infection. 

PMID- 25988889
TI  - Antibody responses to envelope glycoproteins in HIV-1 infection.
AB  - Antibody responses to the HIV-1 envelope glycoproteins can be classified into
      three groups. Binding but non-neutralizing responses are directed to epitopes
      that are expressed on isolated envelope glycoproteins but not on the native
      envelope trimer found on the surface of virions and responsible for mediating the
      entry of virus into target cells. Strain-specific responses and broadly
      neutralizing responses, in contrast, target epitopes that are expressed on the
      native trimer, as revealed by recently resolved structures. The past few years
      have seen the isolation of many broadly neutralizing antibodies of remarkable
      potency that have shown prophylactic and therapeutic activities in animal models.
      These antibodies are helping to guide rational vaccine design and therapeutic
      strategies for HIV-1. 

PMID- 25988899
TI  - TOX sets the stage for innate lymphoid cells.

PMID- 25988900
TI  - A20 is a regulator of necroptosis.

PMID- 25988907
TI  - Genetic structure and forensic parameters of 38 Indels for human identification
      purposes in eight Mexican populations.
AB  - Insertion-deletions for human identification purposes (HID-Indels) offer
      advantages to solve particular forensic situations and complex paternity cases.
      In Mexico, admixed population known as Mestizos is the largest (~90%), plus a
      number of Amerindian groups (~10%), which have not been studied with HID-Indels.
      For this reason, allele frequencies and forensic parameters for 38 HID-Indels
      were estimated in 531 unrelated individuals from one Amerindian (Purepecha) and
      seven Mestizo populations from different regions of the country. Genotype
      distribution was in agreement with Hardy-Weinberg expectations in almost all
      loci/populations. The linkage disequilibrium (LD) test did not reveal possible
      associations between loci pairs in all eight Mexican populations. The combined
      power of discrimination was high in all populations (PD >99.99999999998%).
      However, the power of exclusion of the 38 HID-Indel system (PE >99.6863%) was
      reduced regarding most of autosomal STR kits. The assessment of genetic structure
      (AMOVA) and relationships between populations (FST) demonstrated significant
      differences among Mexican populations, mainly of the Purepecha Amerindian group.
      Among Mexican-Mestizos, three population clusters consistent with geography were
      defined: (i) North-West region: Chihuahua, Sinaloa, and Jalisco; (ii) Central
      Southern region: Mexico City, Veracruz and Yucatan; (iii) South region: Chiapas.
      In brief, this report validates the inclusion of the 38 HID-Indel system in
      forensic casework and paternity cases in seven Mexican-Mestizo populations from
      different regions, and in one Mexican Amerindian group. 

PMID- 25988909
TI  - Full Mouth Implant Rehabilitation with Staged Approach: 6-Year Clinical Follow
      Up.
AB  - OBJECTIVE: The transition of patients from failing dentition to complete arch
      implant rehabilitation often requires that the patient is rendered edentulous and
      has to wear a removable complete denture for varying periods of time. In order to
      avoid removable provisionalization, the staged treatment approach allows for
      fixed interim prosthesis throughout the rehabilitation process, patient comfort,
      and prosthodontic control. CLINICAL CONSIDERATIONS: The purpose of this clinical
      report is to describe a combination of staged approach with guided flapless
      surgery for minimally invasive treatment. The patient had fixed interim
      prostheses during the entire rehabilitation process. The various implant
      prosthodontic stages are illustrated for the complete arch prosthetic
      rehabilitation and the 6-year follow-up outcome is reported. A patient with
      debilitated dentition was treated with this combined protocol and was followed
      for 6 years after definitive prosthesis insertion. CONCLUSION: Implant and
      prosthesis success rates were 100% with minor biologic and no technical
      complications encountered up to 6-year recall. Guided surgery has the advantage
      of prosthetically driven implant placement and minimal postoperative sequelae,
      whereas the staged approach allows for fixed provisionalization throughout the
      entire treatment period. CLINICAL SIGNIFICANCE: As the computer-guided surgery
      protocols continue to evolve and improve, further clinical studies are necessary
      to assess accuracy and make this exciting technology even safer for the average
      clinician. The clinical significance of this case report lies in the treatment
      sequence combined with cutting edge technology for maximum patient comfort and
      prosthodontic control. Guided flapless surgery with prosthodontically driven
      implant placement led to predictable rehabilitation with no major complications
      after 6 years. A staged approach with fixed interim prostheses was used
      throughout the entire rehabilitation period, optimizing patient satisfaction and
      comfort. Natural canine guidance was the occlusal scheme of choice.

PMID- 25988908
TI  - A novel missense NMNAT1 mutation identified in a consanguineous family with Leber
      congenital amaurosis by targeted next generation sequencing.
AB  - Leber congenital amaurosis is the earliest onset and most severe inherited
      retinal dystrophy. Mutations in 21 genes have been identified to be responsible
      for LCA. To detect the causative variants, we performed targeted next generation
      sequencing in two affected siblings of a consanguineous Chinese family with
      suspected LCA. A novel homozygous missense mutation (c.721C>T, p. Pro241Ser) of
      NMNAT1 has been identified. The mutation was inherited from their consanguineous
      parents who were heterozygous and was absent in 300 unrelated healthy
      individuals. NMNAT1, which encodes the nicotinamide mononucleotide
      adenylyltransferase 1, has been recently identified to be one of the LCA-causing
      genes. Our results expanded the spectrum of mutations in NMNAT1. In this study,
      targeted next generation sequencing provides an accurate and efficient method for
      identifying mutations in hereditary diseases with highly genetic and clinical
      heterogeneity. 

PMID- 25988910
TI  - Reduced Water Vapor Transmission Rate of Graphene Gas Barrier Films for Flexible
      Organic Field-Effect Transistors.
AB  - Preventing reactive gas species such as oxygen or water is important to ensure
      the stability and durability of organic electronics. Although inorganic materials
      have been predominantly employed as the protective layers, their poor mechanical
      property has hindered the practical application to flexible electronics. The
      densely packed hexagonal lattice of carbon atoms in graphene does not allow the
      transmission of small gas molecules. In addition, its outstanding mechanical
      flexibility and optical transmittance are expected to be useful to overcome the
      current mechanical limit of the inorganic materials. In this paper, we reported
      the measurement of the water vapor transmission rate (WVTR) through the 6-layer
      10 * 10 cm(2) large-area graphene films synthesized by chemical vapor deposition
      (CVD). The WVTR was measured to be as low as 10(-4) g/m(2).day initially, and
      stabilized at ~0.48 g/m(2).day, which corresponds to 7 times reduction in WVTR
      compared to bare polymer substrates. We also showed that the graphene-passivated
      organic field-effect transistors (OFETs) exhibited excellent environmental
      stability as well as a prolonged lifetime even after 500 bending cycles with
      strain of 2.3%. We expect that our results would be a good reference showing the
      graphene's potential as gas barriers for organic electronics. 

PMID- 25988911
TI  - Klebsiella pneumoniae co-producing NDM-5 and OXA-181 carbapenemases, South Korea.

PMID- 25988912
TI  - Experimental assessment of gold nanoparticle-mediated dose enhancement in
      radiation therapy beams using electron spin resonance dosimetry.
AB  - In this work, we aim to experimentally assess increments of dose due to
      nanoparticle-radiation interactions via electron spin resonance (ESR) dosimetry
      performed with a biological-equivalent sensitive material.We employed 2-Methyl
      Alanine (2MA) in powder form to compose the radiation sensitive medium embedding
      gold nanoparticles (AuNPs) 5 nm in diameter. Dosimeters manufactured with 0.1%
      w/w of AuNPs or no nanoparticles were irradiated with clinically utilized 250 kVp
      orthovoltage or 6 MV linac x-rays in dosimetric conditions. Amplitude peak-to
      peak (App) at the central ESR spectral line was used for dosimetry. Dose-response
      curves were obtained for samples with or without nanoparticles and each energy
      beam. Dose increments due to nanoparticles were analyzed in terms of absolute
      dose enhancements (DEs), calculated as App ratios for each dose/beam condition,
      or relative dose enhancement factors (DEFs) calculated as the slopes of the dose
      response curves.Dose enhancements were observed to present an amplified behavior
      for small doses (between 0.1-0.5 Gy), with this effect being more prominent with
      the kV beam. For doses between 0.5-5 Gy, dose-independent trends were observed
      for both beams, stable around (2.1   +/-   0.7) and (1.3   +/-   0.4) for kV and
      MV beams, respectively. We found DEFs of (1.62   +/-   0.04) or (1.27   +/-  
      0.03) for the same beams. Additionally, we measured no interference between AuNPs
      and the ESR apparatus, including the excitation microwaves, the magnetic fields
      and the paramagnetic radicals.2MA was demonstrated to be a feasible paramagnetic
      radiation-sensitive material for dosimetry in the presence of AuNPs, and ESR
      dosimetry a powerful experimental method for further verifications of increments
      in nanoparticle-mediated doses of biological interest. Ultimately, gold
      nanoparticles can cause significant and detectable dose enhancements in
      biological-like samples irradiated at both kilo or megavoltage beams.

PMID- 25988913
TI  - Comparison of daytime and nighttime new particle growth at the HKUST supersite in
      Hong Kong.
AB  - Particles larger than 50-100 nm in diameter have been considered to be effective
      cloud condensation nuclei (CCN) under typical atmospheric conditions. We studied
      the growth of newly formed particles (NPs) in the atmosphere and the conditions
      for these particles to grow beyond 50 nm at a suburban coastal site in Hong Kong.
      Altogether, 17 new particle formation events each lasting over 1 h were observed
      in 17 days during 8 Mar-28 Apr and 1 Nov-30 Dec 2011. In 12 events, single-stage
      growth of NPs was observed in daytime when the median mobility diameter of NPs
      (Dp) increased up to ~40 nm but did not increase further. In three events, two
      stage particle growth to 61-97 nm was observed at nighttime. The second stage
      growth was preceded by a first-stage growth in daytime when the Dp reached 43 +/-
      4 nm. In all these 15 events, organics and sulfuric acid were major contributors
      to the first-stage growth in daytime. Ammonium nitrate unlikely contributed to
      the growth in daytime, but it was correlated with the second-stage growth of ~40
      nm NPs to CCN sizes at nighttime. The remaining two events apparently showed
      second-stage growth in late afternoon but were confirmed to be due to mixing of
      NPs with pre-existing particles. We conclude that daytime NP growth cannot reach
      CCN sizes at our site, but nighttime NP growth driven by organics and NH4NO3 can.

PMID- 25988914
TI  - Grammar of Binding in the languages of the world: Innate or learned?
AB  - Languages around the world often appear to manifest nearly identical grammatical
      properties, but, at the same time, the grammatical differences can also be great,
      sometimes even seeming to support Joos's (1958) claim that "languages can differ
      from each other without limit and in unpredictable way" (p. 96). This state of
      affairs provides a puzzle for both nativist approaches to language like
      Generative Grammar that posit a fixed "Universal Grammar", and for approaches
      that minimize the contribution of innate grammatical structure. We approach this
      puzzling state of affairs by looking at one area of grammar, "Binding", the
      system of local and long distance anaphoric elements in a language. This is an
      area of grammar that has long been central to the Generative approach to language
      structure. We compare the anaphoric systems found in "familiar" (European-like)
      languages that contain dedicated classes of bound and free anaphors (pronouns and
      reflexives) with the anaphoric systems in endangered Austronesian languages of
      Indonesia, languages in which there is overlap or no distinction between pronouns
      and reflexives (Peranakan Javanese and Jambi Malay). What is of special interest
      about Jambi anaphora is not only that conservative dialects of Jambi Malay do not
      distinguish between pronouns and reflexives, but that Jambi anaphora appear to
      constitute a live snapshot of a unitary class of anaphora in the process of
      grammaticalization as a distinct system of pronouns and reflexives. We argue that
      the facts of Jambi anaphora cannot be explained by theories positing a Universal
      Grammar of Binding. Thus, these facts provide evidence that complex grammatical
      systems like Binding cannot be innate. Our results from Austronesian languages
      are confirmed by data from signed and creole languages. Our conclusion is that
      the human language learning capacity must include the ability to model the full
      complexity found in the syntax of the world's languages. From the perspective of
      child language acquisition, these conclusions suggest that Universal Grammar does
      not provide a general solution to the problem of poverty of the stimulus, and the
      solution to that problem must reside at least in part in special properties of
      the grammar construction tools available to the language learner rather than
      simply in a fixed set of grammatical rules hard wired into the brains of
      speakers. 

PMID- 25988915
TI  - Viewers base estimates of face matching accuracy on their own familiarity:
      Explaining the photo-ID paradox.
AB  - Matching two different images of a face is a very easy task for familiar viewers,
      but much harder for unfamiliar viewers. Despite this, use of photo-ID is
      widespread, and people appear not to know how unreliable it is. We present a
      series of experiments investigating bias both when performing a matching task and
      when predicting other people's performance. Participants saw pairs of faces and
      were asked to make a same/different judgement, after which they were asked to
      predict how well other people, unfamiliar with these faces, would perform. In
      four experiments we show different groups of participants familiar and unfamiliar
      faces, manipulating this in different ways: celebrities in experiments 1-3 and
      personally familiar faces in experiment 4. The results consistently show that
      people match images of familiar faces more accurately than unfamiliar faces.
      However, people also reliably predict that the faces they themselves know will be
      more accurately matched by different viewers. This bias is discussed in the
      context of current theoretical debates about face recognition, and we suggest
      that it may underlie the continued use of photo-ID, despite the availability of
      evidence about its unreliability. 

PMID- 25988917
TI  - Hierarchy of Impairment of Spinal Mobility Measures in Ankylosing Spondylitis:
      Twelve-Year Data.
AB  - OBJECTIVE: To investigate which spinal mobility measures (SMMs) are most
      frequently impaired in patients with ankylosing spondylitis (AS), whether a
      hierarchy of impairment can be established, and whether assessing fewer measures
      sufficiently captures impairment in spinal mobility. METHODS: Patients from the
      Outcome in Ankylosing Spondylitis International Study were followed up for 12
      years. SMMs were considered impaired when falling below predefined cutoffs,
      derived from normal individuals. The proportion of patients in whom each SMM was
      impaired was calculated using baseline observation. In patients with >=1 impaired
      SMM, we investigated how often impairment in spinal mobility would be missed if
      only a fixed number of SMMs was assessed. Analyses were repeated using all 12
      year observations. RESULTS: A total of 216 patients were included (70% males).
      Lateral spinal flexion (LSF) was the most frequently impaired measure, followed
      by the modified Schober (mSchober) test, tragus-to-wall, cervical rotation,
      intermalleolar distance, and chest expansion measures, respectively. This
      hierarchy was strikingly consistent over time, and independent of sex, symptom
      duration, and presence of syndesmophytes. In patients with >=1 impaired SMM, LSF
      was impaired most frequently (86%), followed by the mSchober test (58%). If only
      LSF was measured, 14% of patients with impairment in any SMM would be missed; if
      additionally the mSchober test was measured, 9% would be missed. CONCLUSION: LSF
      followed by the mSchober test are the most frequently impaired mobility measures
      in AS, reflecting an earlier involvement of the lumbar spine, followed by
      involvement of the thoracic and cervical spine. In clinical practice LSF and the
      mSchober test suffice to screen impairment in spinal mobility.

PMID- 25988916
TI  - IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five
      Patients.
AB  - OBJECTIVE: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory
      condition that can affect nearly any organ. Prior studies have focused on
      individual cases of IgG4-RD or small case series. This study was undertaken to
      report detailed clinical and laboratory findings in a larger group of patients
      with IgG4-RD whose diagnosis was established by strict clinicopathologic
      correlation. METHODS: The baseline features of 125 patients with biopsy-proven
      IgG4-RD were reviewed. The diagnosis was confirmed by pathologists' review, based
      on consensus diagnostic criteria and correlation with clinicopathologic features.
      Disease activity and damage were assessed using the IgG4-RD Responder Index (RI).
      Flow cytometry was used to assess levels of circulating plasmablasts. RESULTS: Of
      the 125 patients, 107 had active disease and 86 were not receiving treatment for
      IgG4-RD. Only 51% of the patients with active disease had elevated serum IgG4
      concentrations. However, patients with active disease and elevated serum IgG4
      concentrations were older, had a higher IgG4-RD RI score, a greater number of
      organs involved, lower complement levels, higher absolute eosinophil counts, and
      higher IgE levels compared to those with active disease but normal serum IgG4
      concentrations (P < 0.01 for all comparisons). The correlation between IgG4+
      plasmablast levels and the IgG4-RD RI of disease activity (Spearman's rho = 0.45,
      P = 0.003) was stronger than the correlation between total plasmablast levels and
      the IgG4-RD RI. Seventy-six (61%) of the patients were male, but no significant
      differences according to sex were observed with regard to disease severity, organ
      involvement, or serum IgG4 concentrations. Treatment with glucocorticoids failed
      to produce sustained remission in 77% of patients. CONCLUSION: Nearly 50% of this
      patient cohort with biopsy-proven, clinically active IgG4-RD had normal serum
      IgG4 concentrations. Elevations in the serum IgG4 concentration appeared to
      identify a subset of patients with a more severe disease phenotype. In addition,
      the levels of IgG4+ plasmablasts correlated well with the extent of disease
      activity.

PMID- 25988918
TI  - Hemoglobin detection using carbon dots as a fluorescence probe.
AB  - Herein, we have described the application of high fluorescent carbon dots (CDs)
      without any surface modification as a simple and fast responding fluorescence
      probe for sensitive and selective determination of hemoglobin (Hb) in the
      presence of H2O2. Although Hb itself was able to quench the fluorescence of CDs,
      based on the inner filter effect (IFE) of the protein that affects both
      excitation and emission spectra of CDs, the presence of H2O2 resulted in further
      improvement of the sensitivity of Hb detection. The assay is based on the
      reaction of Hb with H2O2 that generates reactive oxygen species including
      hydroxyl (OH*) and superoxide (O2(*-)) radicals under heme degradation and/or
      iron release from Hb and the subsequent reaction of hydroxyl radicals, as strong
      oxidizing agents, with CDs resulting in high fluorescence quenching. The proposed
      probe was used for determination of Hb in concentration range of 1-100 nM with a
      detection limit of 0.4 nM. The method was successfully applied to the
      determination of Hb in human blood samples.

PMID- 25988919
TI  - Low-density lipoprotein-cholesterol (LDL-C) greater than 100 mg/dL as a quality
      indicator: locating risk in person, place and time.
AB  - RATIONALE, AIMS AND OBJECTIVES: Achieving control over elevated lipid parameters,
      particularly low-density lipoprotein (LDL)-cholesterol, is an acknowledged
      quality indicator in primary care. The Centers for Disease Control and Prevention
      (CDC)'s model for investigation of outbreaks (person-place-time) can be applied
      to the analysis of quality indicators. METHODS: A sample of 322 family medicine
      patients for whom lipid levels were ordered was extracted. LDL > 100 mg/dL was
      cross-tabulated by personal characteristics [age group, gender, body mass index
      (BMI), diagnoses], month (time) and ordering department (place). RESULTS: Age
      (except one age category), gender, time and location were not related to LDL >
      100 mg/dL after adjustment for covariates. All levels of BMI above normal
      elevated the risk of LDL > 100 mg/dL [BMI 25-29.9: odds ratio (OR) = 3.41,
      confidence interval (CI) = 1.61-7.23, P = 0.0014; BMI 30-34.9: OR = 2.93, CI =
      1.28-6.70, P = 0.0109; BMI >= 35: OR = 2.75, CI = 1.19-6.37, P = 0.0181].
      Patients with coronary artery disease (CAD) and diabetes mellitus (DM) were at
      reduced risk for LDL > 100 mg/dL (CAD: OR = 0.47, CI = 0.24-0.91, P = 0.0254; DM:
      OR = 0.28, CI = 0.14-0.55, P = 0.0002). CONCLUSION: An outbreak investigation
      model is useful for analysing variations in this quality indicator. Patients with
      higher BMI and those not diagnosed with CAD or DM type I/II may be considered for
      intensified lipid lowering using quality improvement efforts. These might include
      counselling for lifestyle changes or medication therapy depending upon their
      calculated cardiac risk.

PMID- 25988920
TI  - Coordination of physiological traits involved in drought-induced mortality of
      woody plants.
AB  - Accurate modelling of drought-induced mortality is challenging. A steady-state
      model is presented integrating xylem and phloem transport, leaf-level gas
      exchange and plant carbohydrate consumption during drought development. A
      Bayesian analysis of parameter uncertainty based on expert knowledge and a
      literature review is carried out. The model is tested by combining six data
      compilations covering 170 species using information on sensitivities of xylem
      conductivity, stomatal conductance and leaf turgor to water potential. The
      possible modes of plant failure at steady state are identified (i.e. carbon (C)
      starvation, hydraulic failure and phloem transport failure). Carbon starvation
      occurs primarily in the parameter space of isohydric stomatal control, whereas
      hydraulic failure is prevalent in the space of xylem susceptibility to embolism.
      Relative to C starvation, phloem transport failure occurs under conditions of low
      sensitivity of photosynthesis and high sensitivity of growth to plant water
      status. These three failure modes are possible extremes along two axes of
      physiological vulnerabilities, one characterized by the balance of water supply
      and demand and the other by the balance between carbohydrate sources and sinks.
      Because the expression of physiological vulnerabilities is coordinated, we argue
      that different failure modes should occur with roughly equal likelihood,
      consistent with predictions using optimality theory. 

PMID- 25988921
TI  - Co2(OH)2CO3 Nanosheets and CoO Nanonets with Tailored Pore Sizes as Anodes for
      Lithium Ion Batteries.
AB  - Co2(OH)2CO3 nanosheets were prepared and initially tested as anode materials for
      Li ion batteries. Benefiting from hydroxide and carbonate, the as-prepared sample
      delivered a high reversible capacity of 800 mAh g(-1) after 200 cycles at 200 mA
      g(-1) and long-cycling capability of 400 mAh g(-1) even at 1 A g(-1). Annealed in
      Ar, monoclinic Co2(OH)2CO3 nanosheets were transformed into cubic CoO nanonets
      with rich pores. The pore size had apparent influence on the high-rate
      performances of CoO. CoO with appropriate pore sizes exhibited greatly enhanced
      Li storage performances, stable capacity of 637 mAh g(-1) until 200 cycles at 1 A
      g(-1). More importantly, after many fast charge-discharge cycles, the highly
      porous nanonets were still maintained. Our results indicate that Co2(OH)2CO3
      nanosheets and highly porous CoO nanonets are both promising candidate anode
      materials for high-performance Li ion batteries. 

PMID- 25988922
TI  - My Family's Anti-Tobacco Education (My-FATE) model for Aboriginal and Torres
      Strait Islander peoples.

PMID- 25988923
TI  - Synthesis and evaluation of 3-ylideneoxindole acetamides as potent anticancer
      agents.
AB  - Indirubin, an active component in the traditional Chinese medicine formula
      Danggui Longhui Wan, shows promising anticancer effects. Meisoindigo is an analog
      derived from indirubin, which is less toxic and appears to be even more potent
      against cancer. In considering meisoindigo as a structural template for the
      development of new drugs, we designed and synthesized a series of 3
      ylideneoxindole acetamides as novel anticancer agents. The acetamides were then
      evaluated for in vitro and in vivo anticancer activities. The 3-ylideneoxindole
      acetamides were found to have better anticancer activity than was indirubin-3'
      oxime in several cancer cell lines and also displayed a spectrum of activity
      similar to that of the drug candidate roscovitine, a CDK inhibitor. Among the 3
      ylideneoxindole acetamides, compound 10 showed particularly good efficacy. Cell
      cycle analysis further revealed that compound 10 arrested cells in the G1 phase
      and caused an increase in the sub-G1 population, indicating that the apoptosis
      pathway had been induced. In addition, exposure of cells to compound 10 led to
      the upregulation of the cell-cycle regulator cyclin D1, which was sustained at a
      high level. In contrast, the same compound induced a short-term elevation in the
      level of cyclin E, which was followed by a rapid decrease and the attenuation of
      Rb phosphorylation. Furthermore, a docking model suggests that compound 10 binds
      to the active site of CDK4. In testing the therapeutic potency of compound 10 on
      CT26-xenografted BALB/c mice, a significant reduction in tumor size comparable to
      that of cisplatin was found when administrated via the i.p. route. The mice
      presented no loss of body weight, indicating that this compound possesses low
      toxicity. In the future, we are planning in vivo investigations of these new
      active anticancer agents to better elucidate active mechanisms at the cellular
      level and thus benefit the development of anticancer therapies. 

PMID- 25988924
TI  - Rosai-Dorfman disease with atypical intrascrotal involvement.
AB  - We describe two new cases of Rosai-Dorfman disease with intrascrotal involvement.
      Also known as sinus histiocytosis with massive lymphadenopathy, this is a rare
      entity, usually presenting with massive bilateral cervical lymphadenopathy. It is
      associated with extranodal involvement in up to 40% of cases, commonly in the
      face and neck area. Isolated intrascrotal involvement with no lymphadenopathies
      is extremely rare, and its definitive diagnosis is histopathological. Although
      they are the most frequent type, not all intrascrotal lesions are neoplastic;
      therefore, it is important to know other possible etiologies and their radiogical
      features that might help in the diagnosis. We also review other cases of
      intrascrotal involvement reported in the literature, as well as a review clinical
      features, treatment and prognosis of this entity, and a differential diagnosis of
      solid intrascrotal lesions. 

PMID- 25988925
TI  - Neurodegeneration and sport.
AB  - The recent interest in concussion in sport has resulted in significant media
      focus about chronic traumatic encephalopathy (CTE), although a direct causative
      link(s) between concussion and CTE is not established. Typically, sport-related
      CTE occurs in a retired athlete with or without a history of concussion(s) who
      presents with a constellation of cognitive, mood, and/or behavioral symptoms and
      who has postmortem findings of tau deposition within the brain. There are many
      confounding variables, however, that can account for brain tau deposition,
      including genetic mutations, drugs, normal aging, environmental factors,
      postmortem brain processing, and toxins. To understand the roles of such factors
      in neurodegenerative diseases that may occur in athletes, this article reviews
      some neurodegenerative diseases that may present with similar findings in
      nonathletes. The article also reviews pathological changes identified with normal
      aging, and reviews the pathological findings of CTE in light of all these
      factors. While many of these athletes have a history of exposure to head impacts
      as a part of contact sport, there is insufficient evidence to establish causation
      between sports concussion and CTE. It is likely that many of the cases with
      neuropathological findings represent the normal aging process, the effects of
      opiate abuse, or a variant of frontotemporal lobar degeneration. Whether
      particular genetic causes may place athletes at greater risk of neurodegenerative
      disease is yet to be determined. 

PMID- 25988926
TI  - Second-look surgery for intracranial germ cell tumors.
AB  - BACKGROUND: The role of second-look surgery in intracranial germ cell tumors
      (GCTs) needs to be reviewed. OBJECTIVE: To present our experience of second-look
      surgery in patients with intracranial GCTs who showed less than complete response
      despite normalizing or decreasing tumor markers after chemotherapy. METHODS:
      Retrospective review of 7 patients who underwent second-look surgery for an
      intracranial GCT was performed. RESULTS: Of 23 consecutive patients with newly
      diagnosed intracranial GCTs treated between August 2003 and August 2013, 7
      patients (30%) underwent second-look surgery. The mean age was 9.4 years. The
      initial diagnoses were mixed germ cell tumor in 5 and immature teratoma in 2.
      Second-look surgery was performed after 1 to 3 courses of chemotherapy. Magnetic
      resonance imaging at the surgery demonstrated increasing residual tumor in 4 and
      stable residual tumor in 3. Tumor markers were normalized in 5 and nearly
      normalized in 2. Gross total resection was achieved in all patients.
      Histopathology at second-look surgery revealed mature teratoma in 5, fibrosis
      with atypical cells in 1, and fibrosis in 1. All patients subsequently underwent
      additional chemoradiation therapy according to the initial diagnosis. All
      patients are alive with no evidence of recurrence, with a mean follow-up of 48
      months. CONCLUSION: Second-look surgery plays an important role in the treatment
      of intracranial GCTs. Surgery may be encouraged at a relatively early phase after
      chemotherapy when the residual tumor increases or does not change size despite
      normalized or nearly normalized tumor markers in order to achieve complete
      resection and improve outcome.

PMID- 25988927
TI  - Endovascular treatment and the outcomes of atherosclerotic intracranial stenosis
      in patients with hyperacute stroke.
AB  - BACKGROUND: The importance of underlying atherosclerotic intracranial artery
      stenosis (ICAS) in hyperacute stroke patients who receive endovascular therapy
      remains unknown. OBJECTIVE: To report and compare the outcomes of multimodal
      endovascular therapy in patients with hyperacute stroke with and without
      underlying ICAS. METHODS: A total of 172 consecutive patients with acute stroke
      were treated with multimodal endovascular therapy that was heavily weighted
      toward stent-based thrombectomy. Patients with ICAS underwent emergent
      intracranial angioplasty or stenting. Data were compared between patients with
      and without ICAS. Revascularization was defined as Thrombolysis in Cerebral
      Infarction grade >=2b. A favorable outcome was defined as a modified Rankin Scale
      score <=2 or equal to the premorbid modified Rankin Scale score at 3 months.
      RESULTS: ICAS was responsible for acute ischemic symptoms in 40 patients (22.9%).
      Revascularization and favorable outcome occurred more frequently in the ICAS
      group than in the control group (95% vs 81.8%, P = .04; 65% vs 40.2%, P = .01,
      respectively). The median baseline National Institutes of Health Stroke Scale
      score was significantly lower in the ICAS group compared with the control group
      (10 vs 12; P = .002). There were no significant differences between the 2 groups
      in the rates of symptomatic hemorrhage and mortality. CONCLUSION: Emergent
      intracranial angioplasty with or without stenting is safe and feasible and yields
      a high rate of revascularization and favorable outcome in patients with
      hyperacute stroke and underlying ICAS. Patients with underlying ICAS have less
      severe infarctions at presentation and higher successful revascularization after
      multimodal endovascular therapy in the setting of hyperacute stroke compared with
      those with other stroke subtypes.

PMID- 25988928
TI  - Clinical outcome of children with suspected shunt malfunction evaluated in the
      emergency department.
AB  - BACKGROUND: Patients with cerebrospinal fluid shunts frequently present to the
      emergency department (ED) with suspected shunt malfunction. The outcome of those
      patients who were discharged from ED when shunt malfunction was deemed unlikely
      has not been previously documented. OBJECTIVE: To demonstrate there is no
      increase in severity or likelihood of harm for patients who are discharged
      directly from the ED after adequate evaluation, as compared to patients who were
      selected for inpatient hospitalization. METHODS: The report screens 3080 ED
      visits between 2010 and 2013 made by patients with shunted hydrocephalus. ED
      visits preceded by another ED visit or neurosurgical procedures within 60 days
      were excluded. ED visits for reasons unrelated to shunt function were excluded,
      and 1943 visits met the inclusion criteria. Final dispositions from the ED
      included home (n = 1176), admission to neurosurgery service (n = 550), and
      admission to other services (n = 217). Subsequent events within 30 days,
      including ED visits and elective and nonelective shunt-related surgery, were
      reviewed. RESULTS: The clinical characteristics of the 3 groups were similar. Of
      patients discharged home from the ED, 19.0% returned to ED, and 4.5% required
      shunt-related surgeries. Of the patients admitted for observation, 18.7% returned
      to ED and 14.2% required shunt-related surgery. Of the patients admitted to other
      hospital services, 19.6% patients returned to the ED, with 2.0% requiring
      surgical intervention. There were no shunt-related mortalities in any of the 3
      groups. CONCLUSION: Children with cerebrospinal fluid shunts are often evaluated
      in the ED. Discharge from the ED, when suspicion for shunt malfunction is low, is
      an appropriate practice.

PMID- 25988930
TI  - Does navigated transcranial stimulation increase the accuracy of tractography? A
      prospective clinical trial based on intraoperative motor evoked potential
      monitoring during deep brain stimulation.
AB  - BACKGROUND: Tractography based on diffusion tensor imaging has become a popular
      tool for delineating white matter tracts for neurosurgical procedures. OBJECTIVE:
      To explore whether navigated transcranial magnetic stimulation (nTMS) might
      increase the accuracy of fiber tracking. METHODS: Tractography was performed
      according to both anatomic delineation of the motor cortex (n = 14) and nTMS
      results (n = 9). After implantation of the definitive electrode, stimulation via
      the electrode was performed, defining a stimulation threshold for eliciting motor
      evoked potentials recorded during deep brain stimulation surgery. Others have
      shown that of arm and leg muscles. This threshold was correlated with the
      shortest distance between the active electrode contact and both fiber tracks.
      Results were evaluated by correlation to motor evoked potential monitoring during
      deep brain stimulation, a surgical procedure causing hardly any brain shift.
      RESULTS: Distances to fiber tracks clearly correlated with motor evoked potential
      thresholds. Tracks based on nTMS had a higher predictive value than tracks based
      on anatomic motor cortex definition (P < .001 and P = .005, respectively).
      However, target site, hemisphere, and active electrode contact did not influence
      this correlation. CONCLUSION: The implementation of tractography based on nTMS
      increases the accuracy of fiber tracking. Moreover, this combination of methods
      has the potential to become a supplemental tool for guiding electrode
      implantation.

PMID- 25988929
TI  - Fully automated targeting using nonrigid image registration matches accuracy and
      exceeds precision of best manual approaches to subthalamic deep brain stimulation
      targeting in Parkinson disease.
AB  - BACKGROUND: Finding the optimal location for the implantation of the electrode in
      deep brain stimulation (DBS) surgery is crucial for maximizing the therapeutic
      benefit to the patient. Such targeting is challenging for several reasons,
      including anatomic variability between patients as well as the lack of consensus
      about the location of the optimal target. OBJECTIVE: To compare the performance
      of popular manual targeting methods against a fully automatic nonrigid image
      registration-based approach. METHODS: In 71 Parkinson disease subthalamic nucleus
      (STN)-DBS implantations, an experienced functional neurosurgeon selected the
      target manually using 3 different approaches: indirect targeting using standard
      stereotactic coordinates, direct targeting based on the patient magnetic
      resonance imaging, and indirect targeting relative to the red nucleus. Targets
      were also automatically predicted by using a leave-one-out approach to populate
      the CranialVault atlas with the use of nonrigid image registration. The different
      targeting methods were compared against the location of the final active contact,
      determined through iterative clinical programming in each individual patient.
      RESULTS: Targeting by using standard stereotactic coordinates corresponding to
      the center of the motor territory of the STN had the largest targeting error
      (3.69 mm), followed by direct targeting (3.44 mm), average stereotactic
      coordinates of active contacts from this study (3.02 mm), red nucleus-based
      targeting (2.75 mm), and nonrigid image registration-based automatic predictions
      using the CranialVault atlas (2.70 mm). The CranialVault atlas method had
      statistically smaller variance than all manual approaches. CONCLUSION: Fully
      automatic targeting based on nonrigid image registration with the use of the
      CranialVault atlas is as accurate and more precise than popular manual methods
      for STN-DBS.

PMID- 25988932
TI  - The logistics of choice.
AB  - The generalized matching law (GML) is reconstructed as a logistic regression
      equation that privileges no particular value of the sensitivity parameter, a.
      That value will often approach 1 due to the feedback that drives switching that
      is intrinsic to most concurrent schedules. A model of that feedback reproduced
      some features of concurrent data. The GML is a law only in the strained sense
      that any equation that maps data is a law. The machine under the hood of matching
      is in all likelihood the very law that was displaced by the Matching Law. It is
      now time to return the Law of Effect to centrality in our science. 

PMID- 25988934
TI  - Lack of protection against ebola virus from chloroquine in mice and hamsters.
AB  - The antimalarial drug chloroquine has been suggested as a treatment for Ebola
      virus infection. Chloroquine inhibited virus replication in vitro, but only at
      cytotoxic concentrations. In mouse and hamster models, treatment did not improve
      survival. Chloroquine is not a promising treatment for Ebola. Efforts should be
      directed toward other drug classes. 

PMID- 25988933
TI  - A genome-wide identified risk variant for PTSD is a methylation quantitative
      trait locus and confers decreased cortical activation to fearful faces.
AB  - Genetic factors appear to be highly relevant to predicting differential risk for
      the development of post-traumatic stress disorder (PTSD). In a discovery sample,
      we conducted a genome-wide association study (GWAS) for PTSD using a small
      military cohort (Systems Biology PTSD Biomarkers Consortium; SBPBC, N = 147) that
      was designed as a case-controlled sample of highly exposed, recently returning
      veterans with and without combat-related PTSD. A genome-wide significant single
      nucleotide polymorphism (SNP), rs717947, at chromosome 4p15 (N = 147, beta =
      31.34, P = 1.28 * 10(-8) ) was found to associate with the gold-standard
      diagnostic measure for PTSD (the Clinician Administered PTSD Scale). We conducted
      replication and follow-up studies in an external sample, a larger urban community
      cohort (Grady Trauma Project, GTP, N = 2006), to determine the robustness and
      putative functionality of this risk variant. In the GTP replication sample, SNP
      rs717947 associated with PTSD diagnosis in females (N = 2006, P = 0.005), but not
      males. SNP rs717947 was also found to be a methylation quantitative trait locus
      (meQTL) in the GTP replication sample (N = 157, P = 0.002). Further, the risk
      allele of rs717947 was associated with decreased medial and dorsolateral cortical
      activation to fearful faces (N = 53, P < 0.05) in the GTP replication sample.
      These data identify a genome-wide significant polymorphism conferring risk for
      PTSD, which was associated with differential epigenetic regulation and with
      differential cortical responses to fear in a replication sample. These results
      may provide new insight into understanding genetic and epigenetic regulation of
      PTSD and intermediate phenotypes that contribute to this disorder.

PMID- 25988935
TI  - Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients
      Receiving Everolimus and Reduced Tacrolimus Doses.
AB  - This study compared the incidence of CMV infection/disease in de novo kidney
      transplant recipients receiving everolimus or mycophenolate and no CMV
      pharmacological prophylaxis. We randomized 288 patients to receive a single 3
      mg/kg dose of antithymocyte globulin, tacrolimus, everolimus, and prednisone (r
      ATG/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n
      = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n =
      101). The primary end-point was the incidence of first CMV infection/disease in
      the intention-to-treat population at 12 months. Patients treated with r-ATG/EVR
      showed a 90% proportional reduction (4.7% vs. 37.6%, HR 0.10, 95% CI 0.037-0.29;
      p < 0.001), while those treated with BAS/EVR showed a 75% proportional reduction
      (10.8% vs. 37.6%, HR 0.25, 95% CI 0.13-0.48; p < 0.001) in the incidence of CMV
      infection/disease compared to BAS/MPS. There were no differences in the incidence
      of acute rejection (9.4 vs. 18.6 vs. 15.8%, p = 0.403), wound-healing
      complications, delayed graft function, and proteinuria. Mean estimated glomerular
      filtration rate was lower in BAS/EVR (65.7 +/- 21.8 vs. 60.6 +/- 20.9 vs. 69.5 +/
      21.5 ml/min, p = 0.021). In de novo kidney transplant recipients receiving no
      pharmacological CMV prophylaxis, reduced-dose tacrolimus and everolimus was
      associated with a significant reduction in the incidence of CMV infection/disease
      compared to standard tacrolimus dose and mycophenolate (ClinicalTrials.gov
      NCT01354301).

PMID- 25988936
TI  - Hepatic metallothioneins in molecular responses to cobalt, zinc, and their
      nanoscale polymeric composites in frog Rana ridibunda.
AB  - Despite numerous studies suggesting a dramatic decline of amphibians, the
      biochemical mechanisms of adaptation in these animals to polluted environment are
      poorly studied. The aim of this study was to elucidate the ability to release
      cobalt (Co) and zinc (Zn) from their nanoscale complexes (NCs) derived from the
      polymeric substance of N-vinylpyrrolidone (PS) in the liver of amphibian (Rana
      ridibunda). Frog males were subjected to 14days exposure to waterborne Co(2+)
      (50MUg/L), Zn(2+) (100MUg/L), as well as corresponding concentrations of Co-NC,
      Zn-NC or PS. Main attention was paid to MT's interrelations with indices of
      stress and toxicity. Only Co(2+) and Zn(2+) caused elevation of the correspondent
      metal in MTs. Co(2+) caused down-regulation of cathepsin D activity, while
      Zn(2+), Zn-NC and the PS up-regulated this activity. Zn(2+) provoked 1.6 times
      increase of metal-bounded form of the MT (MT-Me), while all other exposures
      caused the elevation of the ratio of MT total protein concentration (MT-SH) and
      concentrations of the MT-Me and/or immunoreactive (MTi) form (up to ~10 times)
      accompanied by a decrease in the levels of oxyradicals. The increased DNA
      fragmentation and down-regulation of caspase-3 activity in relation to the redox
      state of glutathione and/or lactate/pyruvate were shown at all exposures. These
      data indicate the vulnerability of the redox state of cellular thiols and
      inability to release Co and Zn from NCs in frog's liver. 

PMID- 25988937
TI  - Modern Palliative Treatments for Metastatic Bone Disease: Awareness of
      Advantages, Disadvantages, and Guidance.
AB  - BACKGROUND: Metastatic disease is the most common malignancy of the bone.
      Prostate, breast, lung, kidney, and thyroid cancer account for 80% of skeletal
      metastases. Bone metastases are associated with significant skeletal morbidity
      including severe bone pain, pathologic fractures, spinal cord or nerve roots
      compression, and malignant hypercalcemia. These events compromise greatly the
      quality of life of the patients. The treatment of cancer patients with bone
      metastases is mostly aimed at palliation. OBJECTIVE: This article aims to present
      these palliative treatments for the patients with bone metastases, summarize the
      clinical applications, and review the techniques and results. METHODS: It gives
      an extensive overview of the possibilities of palliation in patients with
      metastatic cancer to the bone. RESULTS AND DISCUSSION: Currently, modern
      treatments are available for the palliative management of patients with
      metastatic bone disease. These include modern radiation therapy, chemotherapy,
      embolization, electrochemotherapy, radiofrequency ablation, and high-intensity
      focused ultrasound. As such it is of interest for all physicians with no
      experience with these developments to make palliative procedures safer and more
      reliable.

PMID- 25988938
TI  - Safety and Efficacy of Needle-free Powder Lidocaine Delivery System in Adult
      Patients Undergoing Venipuncture or Peripheral Venous Cannulation: A Randomized,
      Double-Blind, Placebo-controlled Trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy, safety, and
      tolerability of a needle-free powder lidocaine delivery system compared with sham
      placebo in adults. METHODS: Adult patients participated in this multicenter,
      randomized, double-blind, placebo-controlled, parallel-group study. Patients were
      randomly allocated to receive either the needle-free powder lidocaine delivery
      system or sham placebo 1 to 3 minutes before a required venipuncture or venous
      cannulation. The primary efficacy endpoint measured the analgesic effect of the
      active system using a pain visual analogue scale. RESULTS: In 693 adults who
      completed the study, the needle-free powder lidocaine delivery system was
      associated with significantly less pain during venipuncture and venous
      cannulation compared with sham placebo, as demonstrated by a difference between
      groups in age-adjusted mean pain score (P=0.003). Secondary analyses
      demonstrating significant differences between groups included the proportion of
      patients who were pain free, the proportion of responders, and the difference
      between pain experienced during the current venous procedure compared with the
      recollection of pain experienced during a prior venous procedure. Use of the
      active system was not associated with any serious adverse events or any adverse
      events resulting in study discontinuation. All treatment-related adverse events
      were mild. DISCUSSION: This clinical trial demonstrated that use of a needle-free
      powder lidocaine delivery system resulted in a significant reduction of pain
      during venipuncture and peripheral intravenous cannulation in adults. Both the
      predefined primary endpoint and all 3 secondary endpoints were met. The needle
      free powder lidocaine delivery system may be an option for analgesia during
      venous access procedures in adults.

PMID- 25988939
TI  - Physical Activity to Reduce Systemic Inflammation Associated With Chronic Pain
      and Obesity: A Narrative Review.
AB  - INTRODUCTION: The increasing prevalence of chronic pain and obesity has
      significant health and cost implications for economies in the developed and
      developing world. Evidence suggests that there is a positive correlation between
      obesity and chronic pain and the link between them is thought to be systemic
      inflammation. OBJECTIVES: The aim of this narrative review was to explore the
      physiological links between chronic musculoskeletal pain and obesity and to
      consider the potential role of regular physical activity in providing a means of
      managing obesity-related chronic pain. DISCUSSION: Systemic inflammation,
      mechanical overload, and autonomic dysfunction are associated with increased
      prevalence and severity of chronic pain in individuals with obesity. It has been
      proposed, therefore, that interventions that target systemic inflammation could
      help to reduce chronic pain in obese individuals. Reduction in abdominal fat has
      been shown to alleviate pain and reduce the systemic markers of inflammation that
      contribute to chronic pain. Interventions that include exercise prescription have
      been shown to reduce both abdominal fat and systemic inflammation. Furthermore,
      exercise is also known to reduce pain perception and improve mental health and
      quality of life that also improves pain outcomes. However, adherence to formal
      exercise prescription is poor and therefore exercise programmes should be
      tailored to the interests, needs, and abilities of individuals to reduce
      attrition.

PMID- 25988940
TI  - Triblock Copolymer Nanovesicles for pH-Responsive Targeted Delivery and
      Controlled Release of siRNA to Cancer Cells.
AB  - New pH-responsive polymersomes for active anticancer oligonucleotide delivery
      were prepared from triblock copolymers. The delivery systems were formed by two
      terminal hydrophilic blocks, PEG and polyglycerolmethacrylate (poly-GMA), and a
      central weakly basic block, polyimidazole-hexyl methacrylate (poly-ImHeMA), which
      can complex with oligonucleotides and control vesicle formation/disassembly via
      pH variations. Targeted polymersomes were prepared by mixing folate-derivatized
      and underivatized copolymers. At pH 5, ds-DNA was found to complex with the pH
      responsive copolymers at a N/P molar ratio above ~2:1, which assisted the
      encapsulation of ds-DNA in the polymersomes, while low association was observed
      at pH 7.4. Cytotoxicity studies performed on folate receptor overexpressing KB
      and B16-F10 cells and low folate receptor expressing MCF-7 cells showed high
      tolerance of the polymersomes at up to 3 mg/mL concentration. Studies performed
      with red blood cells showed that at pH 5.0 the polymersomes have endosomolytic
      properties. Cytofluorimetric studies showed a 5.5-fold higher uptake of ds-DNA
      loaded folate-functional polymersomes in KB cells compared to nontargeted
      polymersomes. In addition, ds-DNA was found to be localized both in the nucleus
      and in the cytosol. The incubation of luciferase transfected B16-F10 cells with
      targeted polymersomes loaded with luciferase and Hsp90 expression silencing
      siRNAs yielded 31 and 23% knockdown in target protein expression, respectively.

PMID- 25988941
TI  - Response to low-dose herbicide selection in self-pollinated Avena fatua.
AB  - BACKGROUND: When applied at the correct plant stage and dose, herbicides are
      highly toxic to plants. At reduced, low herbicide doses (below the recommended
      dose) plants can survive and display continuous and quantitative variation in
      dose-survival responses. Recurrent (directional) selection studies can reveal
      whether such a phenotypic variation in plant survival response to low herbicide
      dose is heritable and leads to herbicide resistance. In a common experimental
      garden study, we have subjected a susceptible population of self-pollinated
      hexaploid Avena fatua to low-dose recurrent selection with the ACCase-inhibiting
      herbicide diclofop-methyl for three consecutive generations. RESULTS: Significant
      differences in response to low-dose diclofop-methyl selection were observed
      between the selected progenies and parent plants, with a twofold diclofop-methyl
      resistance and cross-resistance to ALS-inhibiting herbicides. Thus, the capacity
      of self-pollinated A. fatua to respond to low-dose herbicide selection is
      marginal, and it is much lower than in cross-pollinated L. rigidum. Lolium
      rigidum in the same experiment evolved 40-fold diclofop-methyl resistance by
      progressive enrichment of quantitative resistance-endowing traits. CONCLUSION:
      Cross-pollination rate, genetic variation and ploidy levels are identified as
      possible drivers affecting the contrasting capacity of Avena versus Lolium plants
      to respond to herbicide selection and the subsequent likelihood of resistance
      evolution at low herbicide dose usage.

PMID- 25988943
TI  - Association of VDR gene polymorphisms with heart disease in chronic kidney
      disease patients.
AB  - OBJECTIVES: It has been postulated that VDR polymorphisms influence mortality in
      CKD by directly modifying VDR protein levels or VDR sensitivity in target organs.
      Here we aimed at evaluating the possible association of VDR FokI and BsmI gene
      polymorphisms with co-morbid conditions of CKD at different stages. DESIGN AND
      METHODS: The patients included in this study were a Sicilian cohort of 171
      subjects, at CKD stage 1-2 (n=49), stage 3 (n=34), stage 4-5 (n=34), and
      hemodialysis (HD) (n=54). Almost 70% of patients were also suffering from heart
      disease, with/without diabetes and/or hypertension, and 40% were also suffering
      of hypertension, with/without diabetes and/or heart disease; only around 20% had
      no co-morbid conditions. RESULTS: A highly significant association was found
      between the BsmI B minor allele and heart disease in all CKD stages. Indeed, the
      odds ratio calculation showed that patients bearing either the bB or BB genotype
      had, respectively, a seven-fold and around twelve-fold increased risk for heart
      disease. Instead, the presence of bb wild-type genotype was associated with a
      fifty-fold reduced risk for heart disease, suggesting that the b allele may
      display a protective effect. No association was found for FokI genotypes with the
      different co-morbid conditions. CONCLUSIONS: We first demonstrated that the VDR
      BsmI B allele may be considered as a genetic determinant for heart disease and
      hypertension in CKD, independently from disease stage. Thus, the screening for
      VDR variants should be regarded as a way to better address preventive strategies
      and improving the management of CKD co-morbid conditions.

PMID- 25988942
TI  - Sex differences in autism spectrum disorders: does sex moderate the pathway from
      clinical symptoms to adaptive behavior?
AB  - We explored sex differences in diagnostic categories, clinical symptoms and
      adaptive behavior of persons with autism spectrum disorders, as well as sex
      specific correlations of clinical and adaptive caracteristics. The study involved
      108 patients (83 males, 6.73 +/- 4.33 years old) diagnosed with autism spectrum
      disorders (ASD). Assessment included ADI-R and Vineland Adaptive Behavior Scale
      II. Males were more often diagnosed with typical autism. There were no sex
      differences in the autistic symptoms, while females showed better functioning in
      Daily living skills, without reaching statistically significant difference (p =
      0.062). We have found different associations of autistic symptoms with different
      aspects of adaptive behavior in males and females. Social reciprocity in females
      correlated with social domain of adaptive behavior, in a positive direction. Our
      findings have shown that although there are no sex differences in autistic
      symptoms, females tend to be somewhat more functional, and are also less
      frequently diagnosed with typical autism. Our results have also shown that sex
      might moderate the way clinical symptoms are expressed in adaptive behavior.
      Social reciprocity might be the core feature regarding sex differences in ASD.
      Our findings might have diagnostic and therapeutical implications, pointing out
      to the need for individualized, sex-specific treatment in this group of
      disorders. 

PMID- 25988944
TI  - Inhibition of connexin43 improves functional recovery after ischemic brain injury
      in neonatal rats.
AB  - Connexin43 (Cx43) is one of the most abundant gap junction proteins in the
      central nervous system. Abnormal opening of Cx43 hemichannels after ischemic
      insults causes apoptotic cell death. In this study, we found persistently
      increased expression of Cx43 8 h to 7 d after hypoxia/ischemia (HI) injury in
      neonatal rats. Pre-treatment with Gap26 and Gap27, two Cx43 mimetic peptides,
      significantly reduced cerebral infarct volume. Gap26 treatment at 24 h after
      ischemia improved functional recovery on muscle strength, motor coordination, and
      spatial memory abilities. Further, Gap26 inhibited Cx43 expression and reduced
      active astrogliosis. Gap26 interacted and co-localized with Cx43 together in
      brain tissues and cultured astrocytes. After oxygen glucose deprivation, Gap26
      treatment reduced the total Cx43 level in cultured astrocytes; but Cx43 level in
      the plasma membrane was increased. Degradation of Cx43 in the cytoplasm was
      mainly via the ubiquitin proteasome pathway. Concurrently, phosphorylated Akt,
      which phosphorylates Cx43 on Serine(373) and facilitates the forward transport of
      Cx43 to the plasma membrane, was increased by Gap26 treatment. Microdialysis
      showed that increased membranous Cx43 causes glutamate release by opening Cx43
      hemichannels. Extracellular glutamate concentration was significantly decreased
      by Gap26 treatment in vivo. Finally, we found that cleaved caspase-3, an
      apoptosis marker, was attenuated after HI injury by Gap26 treatment. Effects of
      Gap27 were analogous to those of Gap26. In summary, our findings demonstrate that
      modulation of Cx43 expression and astroglial function is a potential therapeutic
      strategy for ischemic brain injury.

PMID- 25988945
TI  - Use of a commercial ELISA for the detection of measles-specific immunoglobulin G
      (IgG) in dried blood spots collected from children living in low-resource
      settings.
AB  - Seroepidemiological monitoring of population immunity to vaccine-preventable
      diseases is critical to prevent future outbreaks. Dried blood spots (DBS), drops
      of capillary blood dried on filter paper, are an affordable, minimally invasive
      alternative to venipuncture for collecting blood in field settings. However, few
      proven methods exist to analyze DBS for the presence of protective antibodies.
      This study validates a novel technique for measuring measles-specific
      immunoglobulin G (IgG) in capillary DBS using a commercial ELISA. The predictive
      performance of a new method for analyzing DBS was tested by comparing matched
      serum and DBS samples from 50 children. The accuracy, precision, and reliability
      of the procedure were evaluated, and the optimal cut points to classify positive
      and negative samples were determined. The method was then applied to 1,588 DBS
      collected during a large survey of children in Mexico and Nicaragua. Measles
      specific IgG in serum samples were 62% negative, 10% equivocal, and 28% positive.
      In comparisons with matched serum, DBS results were 100% sensitive and 96 . 8%
      specific, and agreed in 46 of 50 (92%) cases. The inter-assay and intra-assay
      coefficients of variation from kit-provided controls were greater than desired
      (24.8% and 8.4%, respectively). However, in predictive simulations the average
      misclassification was only 3.9%. Procedures were found to be acceptable to
      surveyors and participants. Analyzing DBS collected in low-resources settings is
      a feasible and accurate means of measuring population immunity to measles and
      should be used to generate objective measures of health status and health system
      performance.

PMID- 25988946
TI  - Selection and characterization of Euglena anabaena var. minor as a new candidate
      Euglena species for industrial application.
AB  - Euglena gracilis is a microalgae used as a model organism. Recently, mass
      cultivation of this species has been achieved for industrial applications. The
      genus Euglena includes more than 200 species that share common useful features,
      but the potential industrial applications of other Euglena species have not been
      evaluated. Thus, we conducted a pilot screening study to identify other species
      that proliferate at a sufficiently rapid rate to be used for mass cultivation; we
      found that Euglena anabaena var. minor had a rapid growth rate. In addition, its
      cells accumulated more than 40% weight of carbohydrate, most of which is
      considered to be a euglenoid specific type of beta-1-3-glucan, paramylon.
      Carbohydrate is stored in E. anabaena var. minor cells during normal culture,
      whereas E. gracilis requires nitrogen limitation to facilitate paramylon
      accumulation. These results suggest the potential industrial application of E.
      anabaena var. minor. 

PMID- 25988948
TI  - Melatonin attenuates impairments of structural hippocampal neuroplasticity in
      OXYS rats during active progression of Alzheimer's disease-like pathology.
AB  - Translational research on Alzheimer's disease (AD) has often focused on reducing
      the high cerebral levels of amyloid-beta (Abeta) as a key characteristic of AD
      pathogenesis. There is, however, a growing body of evidence that synaptic
      dysfunction may be crucial for the development of the most common (sporadic) form
      of AD. The applicability of melatonin (mainly produced by the pineal gland) to
      the treatment of AD is actively evaluated, but usually, such studies are based on
      animal models of early-onset AD, which is responsible for only ~5% of AD cases.
      We have shown previously that in OXYS rats (an established model of sporadic AD),
      accumulation of toxic forms of Abeta in the brain occurs later than does the
      development of signs of neurodegenerative changes and synaptic failure. In this
      regard, recently, we uncovered beneficial neuroprotective effects of melatonin
      (prophylactic dietary supplementation) in OXYS rats. Our aim here was to
      evaluate, starting at the age of active progression of AD-like pathology in OXYS
      rats, the effects of long-term oral administration of melatonin on the structure
      of synapses and on neuronal and glial cells of the hippocampus. Melatonin
      significantly increased hippocampal synaptic density and the number of excitatory
      synapses, decreased the number of inhibitory synapses, and upregulated pre- and
      postsynaptic proteins (synapsin I and PSD-95, respectively). Furthermore,
      melatonin improved the ultrastructure of neuronal and glial cells and reduced
      glial density. Based on our past and present results, the repair of
      neuroplasticity by melatonin is a promising strategy against AD.

PMID- 25988947
TI  - Structural Basis for Error-Free Bypass of the 5-N-Methylformamidopyrimidine-dG
      Lesion by Human DNA Polymerase eta and Sulfolobus solfataricus P2 Polymerase IV.
AB  - N(6)-(2-Deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N
      methylformamidopyrimidine (MeFapy-dG) arises from N7-methylation of
      deoxyguanosine followed by imidazole ring opening. The lesion has been reported
      to persist in animal tissues. Previous in vitro replication bypass investigations
      of the MeFapy-dG adduct revealed predominant insertion of C opposite the lesion,
      dependent on the identity of the DNA polymerase (Pol) and the local sequence
      context. Here we report crystal structures of ternary Pol.DNA.dNTP complexes
      between MeFapy-dG-adducted DNA template:primer duplexes and the Y-family
      polymerases human Pol eta and P2 Pol IV (Dpo4) from Sulfolobus solfataricus. The
      structures of the hPol eta and Dpo4 complexes at the insertion and extension
      stages, respectively, are representative of error-free replication, with MeFapy
      dG in the anti conformation and forming Watson-Crick pairs with dCTP or dC.

PMID- 25988949
TI  - Detection of acute hepatopancreatic necrosis disease strain of Vibrio
      parahaemolyticus using loop-mediated isothermal amplification.

PMID- 25988951
TI  - Scaling for quantum tunneling current in nano- and subnano-scale plasmonic
      junctions.
AB  - When two conductors are separated by a sufficiently thin insulator, electrical
      current can flow between them by quantum tunneling. This paper presents a self
      consistent model of tunneling current in a nano- and subnano-meter metal
      insulator-metal plasmonic junction, by including the effects of space charge and
      exchange correlation potential. It is found that the J-V curve of the junction
      may be divided into three regimes: direct tunneling, field emission, and space
      charge-limited regime. In general, the space charge inside the insulator reduces
      current transfer across the junction, whereas the exchange-correlation potential
      promotes current transfer. It is shown that these effects may modify the current
      density by orders of magnitude from the widely used Simmons' formula, which is
      only accurate for a limited parameter space (insulator thickness > 1 nm and
      barrier height > 3 eV) in the direct tunneling regime. The proposed self
      consistent model may provide a more accurate evaluation of the tunneling current
      in the other regimes. The effects of anode emission and material properties (i.e.
      work function of the electrodes, electron affinity and permittivity of the
      insulator) are examined in detail in various regimes. Our simple model and the
      general scaling for tunneling current may provide insights to new regimes of
      quantum plasmonics.

PMID- 25988952
TI  - Neonatal nurses' beliefs about almost continuous parent-infant skin-to-skin
      contact in neonatal intensive care.
AB  - AIMS AND OBJECTIVES: To describe what nurses believe about almost continuous skin
      to-skin contact for preterm infants between 32(0) -36(0)  weeks gestation.
      BACKGROUND: Skin-to-skin contact a few hours per day has become standard care for
      preterm infants in most high-technology neonatal intensive care units. However,
      few units practice Kangaroo Mother Care which involves almost continuous skin-to
      skin contact. DESIGN: A qualitative descriptive design. METHODS: An online
      questionnaire with open-ended questions was administered to 129 nurses at three
      neonatal units. Data were analysed with qualitative content analysis. FINDINGS:
      Nurses believed they would lose control because of limited access to the infant
      and would not be able to provide adequate care. Nurses also believed that mothers
      practicing almost continuous skin-to-skin contact would feel trapped and would
      experience stress if they could not meet the demands of the method. CONCLUSIONS:
      Although the nurses can describe several of the documented benefits of almost
      continuous skin-to-skin contact, an underuse continues to exist. RELEVANCE FOR
      CLINICAL PRACTICE: Beliefs described by the nurses are important to consider and
      resolve if the goal is to implement and provide Kangaroo Mother Care.

PMID- 25988950
TI  - Bridging the gap between omics and earth system science to better understand how
      environmental change impacts marine microbes.
AB  - The advent of genomic-, transcriptomic- and proteomic-based approaches has
      revolutionized our ability to describe marine microbial communities, including
      biogeography, metabolic potential and diversity, mechanisms of adaptation, and
      phylogeny and evolutionary history. New interdisciplinary approaches are needed
      to move from this descriptive level to improved quantitative, process-level
      understanding of the roles of marine microbes in biogeochemical cycles and of the
      impact of environmental change on the marine microbial ecosystem. Linking studies
      at levels from the genome to the organism, to ecological strategies and organism
      and ecosystem response, requires new modelling approaches. Key to this will be a
      fundamental shift in modelling scale that represents micro-organisms from the
      level of their macromolecular components. This will enable contact with omics
      data sets and allow acclimation and adaptive response at the phenotype level
      (i.e. traits) to be simulated as a combination of fitness maximization and
      evolutionary constraints. This way forward will build on ecological approaches
      that identify key organism traits and systems biology approaches that integrate
      traditional physiological measurements with new insights from omics. It will rely
      on developing an improved understanding of ecophysiology to understand
      quantitatively environmental controls on microbial growth strategies. It will
      also incorporate results from experimental evolution studies in the
      representation of adaptation. The resulting ecosystem-level models can then
      evaluate our level of understanding of controls on ecosystem structure and
      function, highlight major gaps in understanding and help prioritize areas for
      future research programs. Ultimately, this grand synthesis should improve
      predictive capability of the ecosystem response to multiple environmental
      drivers. 

PMID- 25988953
TI  - Improving sixth year medical students' performance in knee arthrocentesis using a
      synthetic knee model.
AB  - AIM: A knee arthrocentesis (KA) workshop using synthetic knee model was arranged
      for all sixth-year medical students (MS) in our institute to ensure equity in
      receiving training. We evaluated confidence level and knowledge of KA and
      synovial fluid analysis testing pre- and post-workshop for MS. METHODS: The
      workshop was divided into two parts. The first part was to provide knowledge in
      arthrocentesis and synovial fluid interpretation and the second was a practice
      session on the synthetic model under supervision. This is a report of pre-and
      post-workshop self-evaluation about the confidence in performing KA (0-10
      scales), improvement of knowledge in KA, and synovial fluid analysis earned from
      attending the workshop. Pearson chi(2) test or Fisher's exact test was used to
      compare categorical variables, where appropriate. RESULTS: There were 247 MS
      attended and 228 (92.3%) evaluated the workshops. Ninety-six (42.1%) MS had
      experience in KA prior to this workshop. The mean (SD) levels of confidence in
      performing the procedure before and after the workshop were 3.6 (2.5) and 7.5
      (1.7), respectively, P < 0.001. Improvement was shown regardless of previous
      exposure to KA. Knowledge of appropriate testing for synovial fluid was
      significantly improved in all items explored after the workshop and extended to
      the better scores earned from a competency examination. CONCLUSIONS: A hands-on
      structured workshop using a synthetic knee model for KA is a successful model for
      improving medical students' confidence in performing the procedure with evidence
      of sustaining knowledge in short-term follow-up.

PMID- 25988954
TI  - Risk factors for acquisition of drug resistance during multidrug-resistant
      tuberculosis treatment, Arkhangelsk Oblast, Russia, 2005-2010.
AB  - Acquired resistance to antituberculosis drugs decreases effective treatment
      options and the likelihood of treatment success. We identified risk factors for
      acquisition of drug resistance during treatment for multidrug-resistant
      tuberculosis (MDR TB) and evaluated the effect on treatment outcomes. Data were
      collected prospectively from adults from Arkhangelsk Oblast, Russia, who had
      pulmonary MDR TB during 2005-2008. Acquisition of resistance to capreomycin and
      of extensively drug-resistant TB were more likely among patients who received <3
      effective drugs than among patients who received >3 effective drugs (9.4% vs. 0%
      and 8.6% vs. 0.8%, respectively). Poor outcomes were more likely among patients
      with acquired capreomycin resistance (100% vs. 25.9%), acquired ofloxacin
      resistance (83.6% vs. 22.7%), or acquired extensive drug resistance (100% vs.
      24.4%). To prevent acquired drug resistance and poor outcomes, baseline
      susceptibility to first- and second-line drugs should be determined quickly, and
      treatment should be adjusted to contain >3 effective drugs. 

PMID- 25988957
TI  - Persistent ascites, leg edema and renal dysfunction after liver transplant.

PMID- 25988959
TI  - Pharmacological actions of nobiletin in the modulation of platelet function.
AB  - BACKGROUND AND PURPOSE: The discovery that flavonoids are capable of inhibiting
      platelet function has led to their investigation as potential antithrombotic
      agents. However, despite the range of studies on the antiplatelet properties of
      flavonoids, little is known about the mechanisms by which flavonoids inhibit
      platelet function. In this study, we aimed to explore the pharmacological effects
      of a polymethoxy flavonoid, nobiletin, in the modulation of platelet function.
      EXPERIMENTAL APPROACH: The ability of nobiletin to modulate platelet function was
      explored by using a range of in vitro and in vivo experimental approaches.
      Aggregation, dense granule secretion and spreading assays were performed using
      washed platelets. Fibrinogen binding, alpha-granule secretion and calcium
      mobilization assays were performed using platelet-rich plasma and whole blood was
      used in impedance aggregometry and thrombus formation experiments. The effect of
      nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6
      mice. KEY RESULTS: Nobiletin was shown to suppress a range of well-established
      activatory mechanisms, including platelet aggregation, granule secretion,
      integrin modulation, calcium mobilization and thrombus formation. Nobiletin
      extended bleeding time in mice and reduced the phosphorylation of PKB (Akt) and
      PLCgamma2 within the collagen receptor (glycoprotein VI)-stimulated pathway, in
      addition to increasing the levels of cGMP and phosphorylation of vasodilator
      stimulated phosphoprotein, a protein whose activity is associated with inhibitory
      cyclic nucleotide signalling. CONCLUSIONS AND IMPLICATIONS: This study provides
      insight into the underlying molecular mechanisms through which nobiletin
      modulates haemostasis and thrombus formation. Therefore, nobiletin may represent
      a potential antithrombotic agent of dietary origins.

PMID- 25988960
TI  - Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants.
AB  - Convenient drug-resistance testing of viral mutants is indispensable to effective
      treatment of viral infection. We developed a novel fluorometric assay for
      phenotypic differentiation of drug-resistant mutants of human immunodeficiency
      virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence
      (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR
      substrates. This assay protocol enables use of non-purified enzyme sources and
      multiple substrates for the enzymatic reaction. In this study, susceptibility of
      HIV mutations to drugs was evaluated by selective formation of three FL products
      after the enzymatic HIV-PR reaction. This proof-of-concept study indicates that
      the present HPLC-FL method could be an alternative to current phenotypic assays
      for the evaluation of HIV drug resistance. 

PMID- 25988961
TI  - Feeling powerless: Locus of control as a potential target for supportive care
      interventions to increase quality of life and decrease anxiety in ovarian cancer
      patients.
AB  - PURPOSE: To evaluate if an individual's locus of control (LOC) predicts various
      quality of life (QOL) and mental well-being measures. To identify targets that
      might enhance the overall spiritual well-being and QOL of ovarian cancer
      patients. METHODS: Multi-site analysis of women with newly diagnosed stages II-IV
      ovarian, primary peritoneal or fallopian tube cancer. Patients completed the
      following surveys: Locus of Control Scale (LOC), Functional Assessment of Chronic
      Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness
      Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment score (ESAS), Hospital
      Anxiety Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), and Herth
      Hope Index (HHI). Regression models were created to examine the effect of LOC
      upon QOL, symptoms, and other measures of mental well-being. These models
      adjusted for the effect of site of care, race, and partnership status as
      potential confounders. RESULTS: This study enrolled 104 patients from three
      separate treatment facilities. After adjusting for site, race and partnership
      status, higher levels of external LOC predicted decreased QOL (FACT-O) (p<0.05).
      Higher levels of external LOC also correlated with increased death anxiety and
      general anxiety (p<=0.05). Additionally, higher levels of external LOC predicted
      decreased hope (HHI) (p<=0.01). DISCUSSION: Ovarian cancer patients with a high
      external LOC may be at risk for decreased QOL at the time of their cancer
      diagnosis. They may also experience higher levels of anxiety and decreased
      feelings of hope. Identification of these women and interventions designed to
      increase a woman's sense of control over her situation may improve QOL and
      overall mental well-being.

PMID- 25988962
TI  - Isoreticular bio-MOF 100-102 coated solid-phase microextraction fibers for fast
      and sensitive determination of organic pollutants by the pore structure dominated
      mechanism.
AB  - Here we report the successful utilization of the stepwise ligand exchange
      strategy for the improvement of adsorption ability of a series of bio-MOFs. The
      fast extraction rate and the different adsorption performances of the three bio
      MOF coatings were dominated by their pore structures. 

PMID- 25988963
TI  - Belinostat (Beleodaq) for peripheral T-Cell lymphoma.

PMID- 25988964
TI  - In brief: mechlorethamine gel (Valchlor) for cutaneous T-Cell lymphoma.

PMID- 25988965
TI  - Pomalidomide (Pomalyst) for multiple myeloma.

PMID- 25988966
TI  - Mood and food.

PMID- 25988968
TI  - Stan Heptinstall and the Erfurt Conferences on Platelets--a personal view.

PMID- 25988969
TI  - Sugary drink consumption and dental caries in New South Wales teenagers.
AB  - BACKGROUND: The consumption of water, milk and various sugary drinks and their
      relationship with the caries experience of a random sample of teenagers aged 14
      to 15 years living in New South Wales, Australia was investigated. METHODS: Data
      were obtained from both clinical and questionnaire components of the NSW Teen
      Dental Survey, 2010. The analyses allowed for various demographic and behavioural
      risk factors using caries experience (DMFT >0) and mean DMFT as the key outcome
      variables. RESULTS: Males were more likely than females to consume large volumes
      of sugary drinks. Consuming two or more glasses of sugary drinks per day led to
      significantly increased caries experience amongst this sample of 14 and 15 year
      olds. Factors found to be associated with elevated sugary drink consumption
      included family income, gender, and mother's education level. CONCLUSIONS: There
      is a strong correlation between increased caries experience of NSW teenagers and
      high levels of consumption of sugary drinks.

PMID- 25988970
TI  - Infantile defences in parent-infant psychotherapy: The example of gaze avoidance.
AB  - Findings from parent-infant observational research have stimulated the
      development of intersubjective models of psychotherapeutic action. These models
      have brought out the infant as an interactive partner with the parent.
      Conversely, interest in describing the individual psyche of the baby has
      decreased, especially the unconscious levels of his/her experiences and
      representations. In parallel, clinicians and researchers have been less prone to
      apply classical psychoanalytic concepts when describing the internal world of the
      infant. The author argues that this is inconsistent with the fact that
      psychoanalytic theory, from its inception, was founded on speculations of the
      infant's mind. He investigates one such concept from classical theory; the
      defence. Specifically, he investigates if selective gaze avoidance in young
      babies may be described as a defence or even a defence mechanism. The
      investigation links with Selma Fraiberg's discussion of the phenomenon and also
      with Freud's conception of defence. The author also compares his views on the
      baby as a subject with those suggested by infant researchers, for example, Stern
      and Beebe. The discussion is illustrated by vignettes from a psychoanalytic
      therapy with a 3 month-old girl and her mother.

PMID- 25988971
TI  - Brief Report: Cryopyrin-Associated Periodic Syndrome Caused by a Myeloid
      Restricted Somatic NLRP3 Mutation.
AB  - OBJECTIVE: To identify the cause of disease in an adult patient presenting with
      recent-onset fevers, chills, urticaria, fatigue, and profound myalgia, who was
      found to be negative for cryopyrin-associated periodic syndrome (CAPS) NLRP3
      mutations by conventional Sanger DNA sequencing. METHODS: We performed whole
      exome sequencing and targeted deep sequencing using DNA from the patient's whole
      blood to identify a possible NLRP3 somatic mutation. We then screened for this
      mutation in subcloned NLRP3 amplicons from fibroblasts, buccal cells,
      granulocytes, negatively selected monocytes, and T and B lymphocytes and further
      confirmed the somatic mutation by targeted sequencing of exon 3. RESULTS: We
      identified a previously reported CAPS-associated mutation, p.Tyr570Cys, with a
      mutant allele frequency of 15% based on exome data. Targeted sequencing and
      subcloning of NLRP3 amplicons confirmed the presence of the somatic mutation in
      whole blood at a ratio similar to the exome data. The mutant allele frequency was
      in the range of 13.3-16.8% in monocytes and 15.2-18% in granulocytes. Notably,
      this mutation was either absent or present at a very low frequency in B and T
      lymphocytes, in buccal cells, and in the patient's cultured fibroblasts.
      CONCLUSION: Our findings indicate the possibility of myeloid-restricted somatic
      mosaicism in the pathogenesis of CAPS, underscoring the emerging role of
      massively parallel sequencing in clinical diagnosis.

PMID- 25988975
TI  - From the Editor. A report from the Harvard Joint Center for Housing Studies.

PMID- 25988972
TI  - The pluripotency factor NANOG promotes the formation of squamous cell carcinomas.
AB  - NANOG is a key pluripotency factor in embryonic stem cells that is frequently
      expressed in squamous cell carcinomas (SCCs). However, a direct link between
      NANOG and SCCs remains to be established. Here, we show that inducible
      overexpression of NANOG in mouse skin epithelia favours the malignant conversion
      of skin papillomas induced by chemical carcinogenesis, leading to increased SCC
      formation. Gene expression analyses in pre-malignant skin indicate that NANOG
      induces genes associated to epithelial-mesenchymal transition (EMT). Some of
      these genes are directly activated by NANOG, including EMT-associated genes Zeb1,
      Zeb2, Twist1, Prrx1 and miR-21. Finally, endogenous NANOG binds to the promoters
      of theses genes in human SCC cells and, moreover, NANOG induces EMT features in
      primary keratinocytes. These results provide in vivo evidence for the oncogenic
      role of NANOG in squamous cell carcinomas. 

PMID- 25988974
TI  - Evaluation of the combined use of the recombinant Brucella abortus Omp10, Omp19
      and Omp28 proteins for the clinical diagnosis of bovine brucellosis.
AB  - Currently, there are several serodiagnostic tools available for brucellosis,
      however, it is difficult to differentiate an active infection from vaccination.
      Hence, there is a great need to develop alternative means that can distinguish
      between these two conditions without utilizing lipopolysaccharide (LPS). This
      study was an attempt to determine the efficacy of combined recombinant Brucella
      (B.) abortus outer membrane proteins (rOmps) and individual rOmps in the
      serodiagnosis of brucellosis by enzyme linked immunosorbent assay (ELISA),
      utilizing both that standard tube agglutination test (TAT)-positive and -negative
      serum samples from Korean native cattle. The results are very interesting and
      promising because the combined rOmp antigens used in the study were highly
      reactive with the TAT-positive serum samples. The combined rOmps sensitivity,
      specificity and accuracy were 215/232 (92.67%), 294/298 (98.66%) and 509/530
      (96.04%), respectively. While these results are preliminary, the tests performed
      have very high potential in the serodiagnosis of brucellosis and likewise, the
      combined rOmps can be used for future vaccine production. 

PMID- 25988979
TI  - Semilunar Coronally Advanced Flap with or without Low Level Laser Therapy in
      Treatment of Human Maxillary Multiple Adjacent Facial Gingival Recessions: A
      Clinical Study.
AB  - PURPOSE: Semilunar coronally advanced flap (SCAF) and its modifications or
      adjuncts have been proposed in the literature for root coverage. Low level laser
      therapy (LLLT) has been shown to enhance wound healing. The aim of this split
      mouth randomized controlled clinical trial was to assess the effects of LLLT
      application with respect to root coverage after SCAF procedure for the treatment
      of human maxillary multiple adjacent facial gingival recessions. MATERIALS AND
      METHODS: Ten subjects with bilateral multiple adjacent maxillary facial gingival
      recession defects (Miller I and II) were included in this study (20 in test, 20
      in control group). A diode laser (810 nm) at 0.3 watts was applied to test sites
      during and 1 week after surgery for 10 seconds. Comparisons of the surgical sites
      were made with clinical measurements. RESULTS: Statistically significant
      differences were observed between test and control sites in the change in
      gingival recession depth, gingival recession width, clinical attachment level,
      and width of the keratinized tissue measurements after 6 months (p = 0.003, p =
      0.001, p = 0.006, and p =< 0.001, respectively). The test group presented
      significantly greater complete root coverage (N = 18/20, 90%) compared with the
      control group (N = 6/20, 30%) at 6 months post-operatively. CONCLUSION: Within
      the confines of this study, the results depicted that a Low Level Laser Technique
      application may enhance the predictability of SCAF procedure. Further long-term
      studies with more sample sizes are needed for a stronger evidence base. CLINICAL
      SIGNIFICANCE: Gingival recessions are commonly encountered in dentistry and pose
      an esthetic concern. Minimal gingival recessions can be treated by a Semilunar
      Coronally Advanced Flap (SCAF), but the predictability and stability of the
      outcomes are quiet questionable. In the present report, a Low Level Laser
      Technique (LLLT) application adjunct to SCAF depicted a significant improvement
      in the predictability and stability of root coverage outcomes (for a period of 6
      months) compared with as achieved by SCAF alone. From this report, it can be
      stated that LLLT may be effectively used in a day to day practice for enhancing
      the root coverage outcomes of SCAF.

PMID- 25988980
TI  - Reliable single sperm cryopreservation in Cell Sleepers for azoospermia
      management.
AB  - Conventional sperm freezing methods perform best when freezing sperm samples
      containing at least hundreds of spermatozoa. In this severe male factor
      infertility case series, we examined the reproductive outcomes in 12
      intracytoplasmic sperm injection cases where spermatozoa used were frozen in Cell
      Sleepers. Cell Sleepers are novel devices in which individual spermatozoa can be
      frozen in microdroplets. The case series included five men with obstructive
      azoospermia, six with nonobstructive azoospermia and one with cryptozoospermia,
      in whom microscopic sperm retrievals from testicular sperm extraction (TESE),
      micro-TESE extracts and a centrifugation procedure resulted in less than 50
      spermatozoa. A total of 304 microscopically retrieved spermatozoa were frozen in
      20 Cell Sleepers using a rapid manual cryopreservation method. A total of 179
      mature oocytes were injected with recovered thawed spermatozoa, resulting in a
      fertilisation rate of 65.9% (118 of 179), with no total fertilisation failures.
      In 10 cases, an embryo transfer was performed, three on day 3 and seven on day 5,
      resulting in a per cycle pregnancy rate of 58.3% (seven of 12). Four of the
      pregnancies have progressed past 20 gestation weeks. The recovery and use of
      spermatozoa that were frozen in Cell Sleepers was uncomplicated and effective and
      eliminated the need to perform any microscopic sperm retrieval procedures on the
      day of oocyte collection. Modification of the routine sperm cryopreservation
      methodology to include the use of Cell Sleepers increases the range of sperm
      samples that can be effectively cryopreserved, to include men with severe male
      factor fertility. 

PMID- 25988981
TI  - [Postoperative Osteomyelitis of a Distal Phalanx Caused by Raoultella
      ornithinolytica].
AB  - We report on a case of osteomyelitis of a distal phalanx of the right ring finger
      of a 62-year-old patient, which occurred 11 months after transosseous-transungual
      refixation of a closed flexor digitorum profundus tendon avulsion caused by
      Raoultella ornithinolytica. R. ornithinolytica is an encapsulated Gram-negative
      aerobic bacillus. In the literature only 13 cases of human infection by R.
      ornithinolytica are mentioned. To the best of our knowledge, this is the first
      case of an osteomyelitis caused by R. ornithinolytica. 

PMID- 25988982
TI  - Academic achievement one year after resective epilepsy surgery in children.
AB  - PURPOSE: Few studies have examined the academic functioning of children following
      pediatric epilepsy surgery. Although intellectual functioning has been more
      thoroughly investigated, children with epilepsy may experience additional
      difficulties with academic skills. This study examined the academic outcomes of a
      cohort of children who underwent pediatric epilepsy surgery on an average 1.2
      (standard deviation [SD]: 0.3) years prior. METHODS: Participants were 136
      children (mean age: 14.3 years, [SD]: 3.7 years) who had undergone resective
      epilepsy surgery. Academic functioning was assessed presurgery and postsurgery
      using standardized tests of reading, reading comprehension, arithmetic, and
      spelling. RESULTS: At baseline, 65% of the children displayed low achievement (1
      SD below test mean), and 28% had underachievement (1 SD below baseline IQ) in at
      least one academic domain. Examining change over time revealed that reading,
      numeral operations, and spelling significantly declined among all patients;
      seizure freedom at follow-up (attained in 64% of the patients) did not influence
      this relationship. Reading comprehension and IQ remained unchanged. Similar
      findings were found when examining patients with a baseline IQ of >= 70 and when
      controlling for IQ. Regression analyses revealed that after controlling for IQ,
      demographic and seizure-related variables were not significantly associated with
      academic achievement at follow-up. CONCLUSIONS: Results show baseline academic
      difficulties and deteriorations following surgery that go beyond IQ. Further
      investigations are required to determine whether the observed deteriorations
      result from the development of the child, the course of the disorder, or the
      epilepsy surgery itself. Long-term studies are warranted to identify the
      progression of academic achievement and whether the observed deteriorations
      represent a temporal disruption in function.

PMID- 25988984
TI  - Salmonella enterica Paratyphi A Infections in Travelers Returning from Cambodia,
      United States.

PMID- 25988983
TI  - The Fricke dosimeter as an absorbed dose to water primary standard for Ir-192
      brachytherapy.
AB  - The aim of this project was to develop an absorbed dose to water primary standard
      for Ir-192 brachytherapy based on the Fricke dosimeter. To achieve this within
      the framework of the existing TG-43 protocol, a determination of the absorbed
      dose to water at the reference position, D(r0,theta0), was undertaken. Prior to
      this investigation, the radiation chemical yield of the ferric ions (G-value) at
      the Ir-192 equivalent photon energy (0.380 MeV) was established by interpolating
      between G-values obtained for Co-60 and 250 kV x-rays.An irradiation geometry was
      developed with a cylindrical holder to contain the Fricke solution and allow
      irradiations in a water phantom to be conducted using a standard Nucletron
      microSelectron V2 HDR Ir-192 afterloader. Once the geometry and holder were
      optimized, the dose obtained with the Fricke system was compared to the standard
      method used in North America, based on air-kerma strength.Initial investigations
      focused on reproducible positioning of the ring-shaped holder for the Fricke
      solution with respect to the Ir-192 source and obtaining an acceptable type A
      uncertainty in the optical density measurements required to yield the absorbed
      dose. Source positioning was found to be reproducible to better than 0.3 mm, and
      a careful cleaning and control procedure reduced the variation in optical density
      reading due to contamination of the Fricke solution by the PMMA holder. It was
      found that fewer than 10 irradiations were required to yield a type A standard
      uncertainty of less than 0.5%.Correction factors to take account of the non-water
      components of the geometry and the volume averaging effect of the Fricke solution
      volume were obtained from Monte Carlo calculations. A sensitivity analysis showed
      that the dependence on the input data used (e.g. interaction cross-sections) was
      small with a type B uncertainty for these corrections estimated to be 0.2%.The
      combined standard uncertainty in the determination of absorbed dose to water at
      the reference position for TG-43 (1 cm from the source on the transverse axis, in
      a water phantom) was estimated to be 0.8% with the dominant uncertainty coming
      from the determination of the G-value. A comparison with absorbed dose to water
      obtained using the product of air-kerma strength and the dose rate constant gave
      agreement within 1.5% for three different Ir-192 sources, which is within the
      combined standard uncertainties of the two methods.

PMID- 25988985
TI  - PPh3.HBr-DMSO: A Reagent System for Diverse Chemoselective Transformations.
AB  - The broad applicability of the hitherto unexplored reagent combination PPh3.HBr
      DMSO is exemplified with multiple highly diverse one-step transformations to
      synthetically useful building blocks, such as flavones, 4H-thiochromen-4-ones,
      alpha-hydroxy ketones, 1,4-naphthoquinones (including vitamin K3), 2-bromo-3
      substituted-1H-1-indenones, 2-methylthio-1H-1-indenones, 3-butyne-1,2-dione, and
      4-pentene-2,3-diones. The simple and mild reaction conditions make the reagent
      superior in terms of yield and substrate scope in comparison with the existing
      alternatives. 

PMID- 25988987
TI  - Orbital Arrangements and Magnetic Interactions in the Quasi-One-Dimensional
      Cuprates ACuMoO4(OH) (A = Na, K).
AB  - A new spin-1/2 quasi-one-dimensional antiferromagnet KCuMoO4(OH) is prepared by
      the hydrothermal method. The crystal structures of KCuMoO4(OH) and the already
      known Na-analogue NaCuMoO4(OH) are isotypic, comprising chains of Cu(2+) ions in
      edge-sharing CuO4(OH)2 octahedra. Despite the structural similarity, their
      magnetic properties are quite different because of the different arrangements of
      dx(2)-y(2) orbitals carrying spins. For NaCuMoO4(OH), dx(2)-y(2) orbitals are
      linked by superexchange couplings via two bridging oxide ions, which gives a
      ferromagnetic nearest-neighbor interaction J1 of -51 K and an antiferromagnetic
      next-nearest-neighbor interaction J2 of 36 K in the chain. In contrast, a
      staggered dx(2)-y(2) orbital arrangement in KCuMoO4(OH) results in superexchange
      couplings via only one bridging oxide ion, which makes J1 antiferromagnetic as
      large as 238 K and J2 negligible. This comparison between the two isotypic
      compounds demonstrates an important role of orbital arrangements in determining
      the magnetic properties of cuprates. 

PMID- 25988988
TI  - Polyarteritis Nodosa of the Iliopsoas Muscle.

PMID- 25988986
TI  - Relationship Between Medial Meniscal Extrusion and Cartilage Loss in Specific
      Femorotibial Subregions: Data From the Osteoarthritis Initiative.
AB  - OBJECTIVE: Medial meniscal extrusion is known to be related to structural
      progression of knee osteoarthritis. However, it is unclear whether medial
      meniscal extrusion is more strongly associated with cartilage loss in certain
      medial femorotibial subregions than in others. METHODS: Segmentation of the
      medial tibial and femoral cartilage (baseline; 1-year followup) and the medial
      meniscus (baseline) was performed in 60 participants with frequent knee pain
      (mean +/- SD ages 61.3 +/- 9.2 years, body mass index 31.3 +/- 3.9 kg/m(2) ) and
      with unilateral medial radiographic joint space narrowing (JSN) grades 1-3, using
      double-echo steady-state magnetic resonance images. Medial meniscal extrusion
      distance and extrusion area (percentage) between the external meniscal and tibial
      margin at baseline, and longitudinal medial cartilage loss in 8 anatomic
      subregions were determined. RESULTS: A significant association (Pearson's
      correlation coefficient) was seen between medial meniscal extrusion area in JSN
      knees and cartilage loss over 1 year throughout the entire medial femorotibial
      compartment. The strongest correlation was with cartilage loss in the external
      medial tibia (r =-0.34, P < 0.01 in JSN; r =-0.30, P = 0.02 in knees without
      JSN). CONCLUSION: Medial meniscal extrusion was associated with subsequent medial
      cartilage loss. The external medial tibial cartilage may be particularly
      vulnerable to thinning once the meniscus extrudes and its surface is exposed to
      direct, nonphysiological, cartilage-to-cartilage contact.

PMID- 25988989
TI  - Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast
      milk: Occurrence, time-course variation and infant health risk.
AB  - Synthetic musk compounds (SMCs) and benzotriazole ultraviolet stabilizers (BUVSs)
      are used as additives in many consumer products. Limited data are available on
      the accumulation of SMCs in human fluids, and no data are available on BUVSs. In
      this study, 208 human breast milk samples were collected from 87 participants
      during the lactation period at <7, 15, 30, and 90 days after delivery in Korea.
      The total concentrations of SMCs and BUVSs ranged from <LOQ to 1593 (median: 286)
      ng/g lipid weight and from <LOQ to 2172 (median: 64.7) ng/g lipid weight,
      respectively. The residue levels of HHCB and AHTN in our samples were the
      highest, compared to those reported in the US, Europe, and China. The predominant
      compounds were HHCB and AHTN for SMCs and UV-328 for BUVSs, consistent with
      consumption patterns of these contaminants. Over the lactation period, no
      significant changes were found in concentrations of SMCs and BUVSs for both
      parity groups. Maternal age, body mass index, and parity were not associated with
      the concentrations of SMCs and BUVSs, while gestational age and delivery mode
      were associated with these contaminants. The estimated daily intakes of HHCB and
      AHTN were lower than the provisional tolerable daily intake values, suggesting a
      limited health risk to Korean infants. This study is the first to comprehensively
      investigate the current levels, accumulation features, contributing factors of
      BUVSs associated with breast milk consumption in Korea.

PMID- 25988991
TI  - Individual daytime noise exposure in different microenvironments.
AB  - BACKGROUND: Numerous studies showed that chronic noise exposure modeled through
      noise mapping is associated with adverse health effects. However, knowledge about
      real individual noise exposure, emitted by several sources, is limited.
      OBJECTIVES: To explain the variation in individual daytime noise exposure
      regarding different microenvironments, activities and individual characteristics.
      MATERIALS AND METHODS: In a repeated measures study in Augsburg, Germany (March
      2007-December 2008), 109 individuals participated in 305 individual noise
      measurements with a mean duration of 5.5h. Whereabouts and activities were
      recorded in a diary. One-minute averages of A-weighted equivalent continuous
      sound pressure levels (Leq) were determined. We used mixed additive models to
      elucidate the variation of Leq by diary-based information, baseline
      characteristics and time-invariant variables like long-term noise exposure.
      RESULTS: Overall noise levels were highly variable (median: 64 dB(A); range: 37
      105 dB(A)). Highest noise levels were measured in traffic during bicycling (69
      dB(A); 49-97 dB(A)) and lowest while resting at home (54 dB(A); 37-94 dB(A)).
      Nearly all diary-based information as well as physical activity, sex and age
      group had significant influences on individual noise. In an additional analysis
      restricted to times spent at the residences, long-term noise exposure did not
      improve the model fit. CONCLUSIONS: Individual exposures to day-time noise were
      moderate to high and showed high variations in different microenvironments except
      when being in traffic. Individual noise levels were greatly determined by
      personal activities but also seemed to depend on environmental noise levels.

PMID- 25988990
TI  - Fine particulate air pollution, nitrogen dioxide, and systemic autoimmune
      rheumatic disease in Calgary, Alberta.
AB  - OBJECTIVE: To estimate the association between fine particulate (PM2.5) and
      nitrogen dioxide (NO2) pollution and systemic autoimmune rheumatic diseases
      (SARDs). METHODS: Associations between ambient air pollution (PM2.5 and NO2) and
      SARDs were assessed using land-use regression models for Calgary, Alberta and
      administrative health data (1993-2007). SARD case definitions were based on >=2
      physician claims, or >=1 rheumatology billing code; or >=1 hospitalization code
      (for systemic lupus, Sjogren's Syndrome, scleroderma, polymyositis,
      dermatomyositis, or undifferentiated connective tissue disease). Bayesian
      hierarchical latent class regression models estimated the probability that each
      resident was a SARD case, based on these case definitions. The sum of individual
      level probabilities provided the estimated number of cases in each area. The
      latent class model included terms for age, sex, and an interaction term between
      age and sex. Bayesian logistic regression models were used to generate adjusted
      odds ratios (OR) for NO2 and PM2.5. pollutant models, adjusting for neighbourhood
      income, age, sex, and an interaction between age and sex. We also examined models
      stratified for First-Nations (FN) and non-FN subgroups. RESULTS: Residents that
      were female and/or aged >45 had a greater probability of being a SARD case, with
      the highest OR estimates for older females. Independently, the odds of being a
      SARDs case increased with PM2.5 levels, but the results were inconclusive for
      NO2. The results stratified by FN and non-FN groups were not distinctly
      different. CONCLUSION: In this urban Canadian sample, adjusting for demographics,
      exposure to PM2.5 was associated with an increased risk of SARDs. The results for
      NO2 were inconclusive.

PMID- 25988992
TI  - Parental oxytocin responses during skin-to-skin contact in pre-term infants.
AB  - OBJECTIVE: Maternal skin-to-skin contact (M-SSC) has been found to reduce adverse
      consequences of prematurity, however, its neurobiological mechanisms have been
      unknown. The purpose of the study was to examine oxytocin mechanism in modulating
      parental stress and anxiety during M-SSC and P-SSC (paternal SSC) with their pre
      term infants. METHODS: Twenty-eight stable pre-term infants and their parents
      (triads) were recruited in a 2-day cross-over study and 26 mothers and 19 fathers
      completed the study protocol. Each triad was randomly assigned to one of the two
      sequences: M-SSC was conducted on day-1 and P-SSC on day-2; and P-SSC on day-1
      and M-SSC on day-2. Parents' saliva samples for oxytocin and cortisol assays and
      visual analog anxiety levels were collected pre-SSC, 30-min during-SSC, and 30
      min post-SSC. RESULTS: Both maternal and paternal oxytocin levels were
      significantly increased during-SSC from baseline. Maternal oxytocin dropped post
      M-SSC, but paternal oxytocin continued to be maintained at a higher level during
      post-P-SSC. Both maternal and paternal cortisol levels significantly decreased
      during-SSC from baseline. Maternal cortisol continuously dropped post-M-SSC, but
      paternal cortisol increased post-P-SSC. Both mothers' and fathers' anxiety levels
      decreased during-SSC from baseline, and then increased post-SSC. Mother-father
      dyads also showed correlated or synchronized stress and anxiety responses in the
      NICU. CONCLUSION: M-SSC and P-SSC activated the oxytocin release and reduced
      stress and anxiety responses in mothers and fathers of pre-term infants. PRACTICE
      IMPLICATIONS: SSC plays a positive role in early post-partum period and patterns
      of maternal and paternal bio-behavioral responses to SSC with pre-term infants
      might be different.

PMID- 25988993
TI  - Clinical practice in line with evidence? A survey among primary care
      physiotherapists in western Sweden.
AB  - RATIONALE, AIMS AND OBJECTIVES: Evidence-based practice is becoming increasingly
      important in primary care physiotherapy. Clinical practice needs to reflect
      current best evidence and be concordant with evidence-based clinical guidelines.
      There is limited knowledge about therapeutic interventions used in primary care
      physiotherapy in Sweden. The objectives were to examine preferred treatment
      interventions reported by publicly employed physiotherapists in primary care for
      three common musculoskeletal disorders (low back pain, neck pain and subacromial
      pain), the extent to which these interventions were supported by evidence, and
      associations with demographic variables. METHODS: 419 physiotherapists in primary
      care in western Sweden were surveyed using a validated web-based questionnaire.
      RESULTS: The survey was completed by 271 respondents (65%). Median number of
      interventions reported was 7 (range 1-16). The most common treatment
      interventions across the three conditions were advice on posture (reported by 82
      94%), advice to stay active (86-92%), and different types of exercise (65-92%).
      Most of these interventions were supported by evidence. However, interventions
      with insufficient evidence, such as advice on posture, TENS and aquatic exercise,
      were also used by 29-96%. Modalities such as laser therapy and ultrasound were
      sparingly used (<5%), which is in line with evidence. For neck pain, use of
      evidence-based interventions was associated with gender and for subacromial pain,
      with work experience. CONCLUSIONS: Advice and exercise therapy were the
      interventions most frequently reported across the three diagnoses, illustrating
      an active treatment strategy. While most reported interventions are supported by
      evidence, interventions with unclear or no evidence of effect were also used to a
      high extent.

PMID- 25988994
TI  - Development and evaluation of training in culturally specific screening and brief
      intervention for hospital patients with alcohol-related injuries.
AB  - OBJECTIVE: To evaluate health practitioners' confidence and knowledge of alcohol
      screening, brief intervention and referral after training in a culturally adapted
      intervention on alcohol misuse and well-being issues for trauma patients. DESIGN:
      Mixed methods, involving semi-structured interviews at baseline and a post
      workshop questionnaire. SETTING: Targeted acute care within a remote area major
      tertiary referral hospital. PARTICIPANTS: Ten key informants and 69 questionnaire
      respondents from relevant community services and hospital-based health care
      professionals. INTERVENTION: Screening and brief intervention training workshops
      and resources for 59 hospital staff. MAIN OUTCOME MEASURES: Self-reported staff
      knowledge of alcohol screening, brief intervention and referral, and satisfaction
      with workshop content and format. RESULTS: After training, 44% of participants
      reported being motivated to implement alcohol screening and intervention.
      Satisfaction with training was high, and most participants reported that their
      knowledge of screening and brief intervention was improved. CONCLUSION: Targeted
      educational interventions can improve the knowledge and confidence of inpatient
      staff who manage patients at high risk of alcohol use disorder. Further research
      is needed to determine the duration of the effect and influence on practice
      behaviour. Ongoing integrated training, linked with systemic support and
      established quality improvement processes, is required to facilitate sustained
      change and widespread dissemination.

PMID- 25988995
TI  - Gold nanoparticle incorporated inverse opal photonic crystal capillaries for
      optofluidic surface enhanced Raman spectroscopy.
AB  - Novel transducers are needed for point of care testing (POCT) devices which aim
      at facile, sensitive and quick acquisition of health related information. Recent
      advances in optofluidics offer tremendous opportunities for biological/chemical
      analysis using extremely small sample volumes. This paper demonstrates
      nanostructured capillary tubes for surface enhanced Raman spectroscopy (SERS)
      analysis in a flow-through fashion. The capillary tube integrates the SERS sensor
      and the nanofluidic structure to synergistically offer sample delivery and
      analysis functions. Inside the capillary tube, inverse opal photonic crystal (IO
      PhC) was fabricated using the co-assembly approach to form nanoscale liquid
      pathways. In the nano-voids of the IO PhC, gold nanoparticles were in situ
      synthesized and functioned as the SERS hotspots. The advantages of the flow
      through SERS sensor are multifold. The capillary effect facilities the sample
      delivery process, the nanofluidic channels boosts the interaction of analyte and
      gold nanoparticles, and the PhC structure strengthens the optical field near the
      SERS hotspots and results in enhanced SERS signals from analytes. As an exemplary
      demonstration, the sensor was used to measure creatinein spiked in artificial
      urine samples with detection limit of 0.9 mg/dL.

PMID- 25988996
TI  - A colorimetric and ratiometric fluorescent probe for selective detection and
      cellular imaging of glutathione.
AB  - A new colorimetric and ratiometric fluorescent probe 1 based on a chlorinated
      coumarinyl aldehyde was developed for selective detection and cellular imaging of
      glutathione (GSH) over cysteine (Cys) and homocysteine (Hcy). Probe 1 exhibits a
      dramatic colorimetric and ratiometric fluorescence responses toward biothiols
      Cys, Hcy and GSH with high selectivity over other amino acids. Cys (or Hcy)
      induces a tandem SNAr-rearrangement reaction to form the corresponding amino
      coumarins (2a or 2b), which result in about 75 nm and 35 nm blue-shifts in
      absorption and emission, respectively. By comparison, the thio-coumarin (3')
      derived from the SNAr reaction with GSH, which does not occur rearrangement
      because of steric hindrance, undergoes an intramolecular aldimine condensation
      lead to a cyclic iminium cation (3) with 47 nm and 39 nm red-shifts in absorption
      and emission, respectively. The significantly difference of photophysical
      properties enable excellent selectivity towards GSH over Cys and Hcy. Further
      application to cellular imaging indicates that the probe has appreciable cell
      permeability and is highly responsive to the changes of GSH level. As a result,
      it is applicable to monitor GSH level in living cells.

PMID- 25988997
TI  - Enhancing the Reactivity of Al/CuO Nanolaminates by Cu Incorporation at the
      Interfaces.
AB  - In situ deposition of a thin (~5 nm) layer of copper between Al and CuO layers is
      shown to increase the overall nanolaminate material reactivity. A combination of
      transmission electron microscopy imaging, in situ infrared spectroscopy, low
      energy ion scattering measurements, and first-principles calculations reveals
      that copper spontaneously diffuses into aluminum layers (substantially less in
      CuO layers). The formation of an interfacial Al:Cu alloy with melting temperature
      lower than pure Al metal is responsible for the enhanced reactivity, opening a
      route to controlling the stochiometry of the aluminum layer and increasing the
      reactivity of the nanoenergetic multilayer systems in general. 

PMID- 25988998
TI  - Dominant gain-of-function mutations in transmembrane domain III of ERS1 and ETR1
      suggest a novel role for this domain in regulating the magnitude of ethylene
      response in Arabidopsis.
AB  - Prior work resulted in identification of an Arabidopsis mutant, eer5-1, with
      extreme ethylene response in conjunction with failure to induce a subset of
      ethylene-responsive genes, including AtEBP. EER5, which is a TREX-2 homolog that
      is part of a nucleoporin complex, functions as part of a cryptic aspect of the
      ethylene signaling pathway that is required for regulating the magnitude of
      ethylene response. A suppressor mutagenesis screen was carried out to identify
      second site mutations that could restore the growth of ethylene-treated eer5-1 to
      wild-type levels. A dominant gain-of-function mutation in the ethylene receptor
      ETHYLENE RESPONSE SENSOR 1 (ERS1) was identified, with the ers1-4 mutation being
      located in transmembrane domain III at a point nearly equivalent to the
      previously described etr1-2 mutation in the other Arabidopsis subfamily I
      ethylene receptor, ETHYLENE RESPONSE 1 (ETR1). Although both ers1-4 and etr1-2
      partially suppress the ethylene hypersensitivity of eer5-1 and are at least in
      part REVERSION TO ETHYLENE SENSITIVITY 1 (RTE1)-dependent, ers1-4 was
      additionally found to restore the expression of AtEBP in ers1-4;eer5-1 etiolated
      seedlings after ethylene treatment in an EIN3-dependent manner. Our work
      indicates that ERS1-regulated expression of a subset of ethylene-responsive genes
      is related to controlling the magnitude of ethylene response, with hyperinduction
      of these genes correlated with reduced ethylene-dependent growth inhibition. 

PMID- 25988999
TI  - Human activities and microbial geographies. An anthropological approach to the
      risk of infections in West African hospitals.
AB  - In hospital care, management of the risk of infection represents a crucial issue.
      Nevertheless, this question remains a neglected area in anthropological research,
      especially in African countries. To shed new light on this question, we conducted
      an anthropological investigation in the infectious disease department of a
      hospital in Niger. Daily observation of the work of the hospital staff for a
      total period of 6 months was spread out over 2008 and 2009. During our prolonged
      stay, we also collected 64 in-depth interviews of health care workers and
      attendants in the department. This study method made it possible to describe many
      of the practices and discourses related to the issues of medical and personal
      care and hospital hygiene and to compare the practices observed to standard
      principles for preventing hospital-acquired infections. Our ethnographic
      attention to the behavior of the actors showed the absence of formal spatial
      segmentations between different activities. The care provided by the untrained
      relatives serving as personal attendants introduced territorial enclaves governed
      by home hygiene standards into the interior of technical spaces. At the same
      time, privatizing equipment and space for their diverse activities, the medical
      staff disrupted technical chains and generated the recurrent crossing of
      microbial geographies. These results allow us to offer two principal guidelines
      for improving the quality of care and the management of risks of infection in
      hospitals in West Africa: (1) the essential role of the attendants in the care
      provided to hospital inpatients must be officially taken into account, especially
      by including them in the organization of medical hygiene procedures; (2) the
      different overlapping technical activities and social activities in the work
      space must be limited by their geographic and architectural segmentation. 

PMID- 25989000
TI  - Epidemics in Ming and Qing China: Impacts of changes of climate and economic well
      being.
AB  - We investigated the mechanism of epidemics with the impacts of climate change and
      socio-economic fluctuations in the Ming and Qing Dynasties in China (AD 1368
      1901). Using long-term and high-quality datasets, this study is the first
      quantitative research that verifies the 'climate change -> economy -> epidemics'
      mechanism in historical China by statistical methods that include correlation
      analysis, Granger causality analysis, ARX, and Poisson-ARX modeling. The analysis
      provides the evidences that climate change could only fundamentally lead to the
      epidemics spread and occurrence, but the depressed economic well-being is the
      direct trigger of epidemics spread and occurrence at the national and long term
      scale in historical China. Moreover, statistical modeling shows that economic
      well-being is more important than population pressure in the mechanism of
      epidemics. However, population pressure remains a key element in determining the
      social vulnerability of the epidemics occurrence under climate change. Notably,
      the findings not only support adaptation theories but also enhance our confidence
      to address climatic shocks if economic buffering capacity can be promoted
      steadily. The findings can be a basis for scientists and policymakers in
      addressing global and regional environmental changes. 

PMID- 25989001
TI  - Occupational closure in nursing work reconsidered: UK health care support workers
      and assistant practitioners: A focus group study.
AB  - In healthcare, occupational groups have adopted tactics to maintain autonomy and
      control over their areas of work. Witz described a credentialist approach to
      occupational closure adopted by nursing in the United Kingdom during the 19th and
      early 20th centuries. However, the recent advancement of assistant, 'non
      qualified' workers by governments and managers forms part of a reconfiguration of
      traditional professional work. This research used focus groups with three cohorts
      of healthcare support workers undertaking assistant practitioner training at a
      London university from 2011 to 13 (6 groups, n = 59). The aim was to examine how
      these workers positioned themselves as professionals and accounted for
      professional boundaries. A thematic analysis revealed a complex situation in
      which participants were divided between articulating an acceptance of a
      subordinate role within traditional occupational boundaries and a usurpatory
      stance towards these boundaries. Participants had usually been handpicked by
      managers and some were ambitious and confident in their abilities. Many aspired
      to train to be nurses claiming that they will gain recognition that they do not
      currently get but which they deserve. Their scope of practice is based upon their
      managers' or supervisors' perception of their individual aptitude rather than on
      a credentialist claim. They 'usurp' nurses claim to be the healthcare worker with
      privileged access to patients, saying they have taken over what nursing has
      considered its core work, while nurses abandon it for largely administrative
      roles. We conclude that the participants are the not unwilling agents of a
      managerially led project to reshape the workforce that cuts across existing
      occupational boundaries. 

PMID- 25989002
TI  - From substance use to homelessness or vice versa?
AB  - Homelessness is associated with substance use, but whether substance use precedes
      or follows homelessness is unclear. We investigate the nature of the relationship
      between homelessness and substance use using data from the unique Australian
      panel dataset Journeys Home collected in 4 surveys over the period from October
      2011 to May 2013. Our data refer to 1325 individuals who were homeless or at risk
      of becoming homeless. We investigate dynamics in homelessness and substance use
      over the survey period. We find that the two are closely related: homeless
      individuals are more likely to be substance users and substance users are more
      likely to be homeless. These relationships, however, are predominantly driven by
      observed and unobserved individual characteristics which cause individuals to be
      both more likely to be homeless and to be substance users. Once we take these
      personal characteristics into account it seems that homelessness does not affect
      substance use, although we cannot rule out that alcohol use increases the
      probability that an individual becomes homeless. These overall relationships also
      hide some interesting heterogeneity by 'type' of homelessness. 

PMID- 25989003
TI  - Choice and compassion at the end of life: A critical analysis of recent English
      policy discourse.
AB  - End of life care in England has recently been framed by two very different
      discourses. One (connected to advance care planning) promotes personal choice,
      the other promotes compassionate care; both are prominent in professional, policy
      and media settings. The article outlines the history of who promoted each
      discourse from 2008 to early 2015, when, why and how and this was done. Each
      discourse is then critically analysed from a standpoint that takes account of
      bodily decline, structural constraints, and human relationality. We focus on the
      biggest group of those nearing the end of their life, namely frail very old
      people suffering multiple conditions. In their care within contemporary
      healthcare organisations, choice becomes a tick box and compassion a commodity.
      Informed choice, whether at the end of life or in advance of it, does not
      guarantee the death the person wants, especially for those dying of conditions
      other than cancer and in the absence of universally available skilled and
      compassionate care. Enabling healthcare staff to provide compassionate,
      relational care, however, implies reversing the philosophical, political and
      financial direction of healthcare in the UK and most other Anglophone countries. 

PMID- 25989005
TI  - Richard Hader Visionary Leader Award.

PMID- 25989004
TI  - Laparoscopic off-clamp partial nephrectomy using soft coagulation.
AB  - OBJECTIVES: To assess the effectiveness of soft coagulation in off-clamp
      laparoscopic partial nephrectomy. METHODS: A total of 32 patients with renal
      tumors underwent laparoscopic partial nephrectomy with off-clamp using soft
      coagulation between May 2012 and September 2013. Tumor resection was carried out
      using a combination of bipolar forceps and a ball electrode using the soft
      coagulation system without hilar clamping. The outcomes of these patients were
      compared with those of 30 patients treated with hilar clamping. RESULTS: This off
      clamp procedure was successfully completed in 31 cases. No significant
      differences were observed in the mean age (60 vs 61 years), sex (male/female;
      25/7 vs 20/10), mean RENAL nephrometry score (5.7 vs 5.8), mean body mass index
      (24.4 vs 23) or tumor size (15 mm vs 16 mm) between the two groups. No
      significant differences were noted in positive surgical margins (0 vs 0) or blood
      loss (104 vs 115 cc) as well. In contrast, a significant difference was noted in
      the total operative time (278 vs 238 min). Serum creatinine percentage changes at
      3 months were 6.4 versus 7.3% in the off-clamp and hilum-clamp groups,
      respectively, which were not significantly different. CONCLUSIONS: Off-clamp
      laparoscopic partial nephrectomy can be safely carried out by using a soft
      coagulation technique.

PMID- 25989006
TI  - Telehealth: Enhancing collaboration, improving care coordination.

PMID- 25989007
TI  - Challenges facing older adults in continued education.

PMID- 25989008
TI  - TeamSTEPPS implementation in the LD/NICU settings.

PMID- 25989009
TI  - A closer look at this specialty.

PMID- 25989011
TI  - Let's talk about it: Communication and a healthy work environment.

PMID- 25989012
TI  - Mental health tips for nurse managers.

PMID- 25989013
TI  - Patient handling and time outs: The way to sustain safety.

PMID- 25989014
TI  - The ART of maintaining the "care" in healthcare.

PMID- 25989015
TI  - Leadership Q&A: Becoming a chairperson.

PMID- 25989016
TI  - Steady-state choice between four alternatives obeys the constant-ratio rule.
AB  - We investigated why violations to the constant-ratio rule, an assumption of the
      generalized matching law, occur in procedures that arrange frequent changes to
      reinforcer ratios. Our investigation produced steady-state data and compared them
      with data from equivalent, frequently changing procedures. Six pigeons responded
      in a four-alternative concurrent-schedule experiment with an arranged reinforcer
      rate ratio of 27:9:3:1. The same four variable-interval schedules were used in
      every condition, for 50 sessions, and the physical location of each schedule was
      changed across conditions. The experiment was a steady-state version of a
      frequently changing procedure in which the locations of four VI schedules were
      changed every 10 reinforcers. We found that subjects' responding was consistent
      with the constant-ratio rule in the steady-state procedure. Additionally, local
      analyses showed that preference after reinforcement was towards the alternative
      that was likely to produce the next reinforcer, instead of being towards the just
      reinforced alternative as in frequently changing procedures. This suggests that
      the effect of a reinforcer on preference is fundamentally different in rapidly
      changing and steady-state environments. Comparing this finding to the existing
      literature suggests that choice is more influenced by reinforcer-generated
      signals when the reinforcement contingencies often change. 

PMID- 25989017
TI  - Wohlfahrtiimonas chitiniclastica Bacteremia Associated with Myiasis, United
      Kingdom.

PMID- 25989019
TI  - Biosciences in nurse education: is the curriculum fit for practice? Lecturers'
      views and recommendations from across the UK.
AB  - AIMS AND OBJECTIVES: This study aims to review the biosciences component of
      preregistration nursing programmes in higher education institutions across the UK
      through the experiences and perceptions of lecturers involved in nursing
      education. BACKGROUND: Studies suggest that some qualified nurses lack confidence
      in explaining the bio-scientific rationale for their clinical practice.
      Biosciences can be difficult to understand and integrate into clinical decision
      making and require protected time within preregistration nurse education. In the
      absence of explicit national guidelines, it is unclear as to the depth and extent
      biosciences are taught across different institutions and the level achieved at
      the point of registration. DESIGN: A survey approach was adopted to generate
      quantitative and qualitative feedback. METHODS: Data were collected using a semi
      structured questionnaire seeking the experiences and views of lecturers involved
      in teaching biosciences to nursing students across the UK. Data received from 10
      institutions were analysed using descriptive statistics and thematic analysis.
      RESULTS: Lecturers reported that the hours of taught biosciences ranged from 20
      113 hours, principally within the first year. This represents between 0.4-2.4% of
      time within a preregistration nursing programme (4600 hours). Large group
      lectures predominate, supplemented by smaller group or practical work, and online
      materials. The biosciences are assessed specifically in half the institutions
      surveyed and as part of integrated assessments in the rest. In relation to
      student feedback, all respondents stated that students consistently requested
      more time and greater priority for biosciences in their programme. CONCLUSIONS:
      This survey suggests that the number of hours spent teaching biosciences is
      minimal and varies widely between higher education institutions. All respondents
      expressed concern about the challenges of teaching difficult bio-scientific
      concepts to large groups in such a limited time and called for greater clarity in
      national guidelines to ensure that all nurses are adequately educated and
      assessed in bioscience subjects. RELEVANCE TO CLINICAL PRACTICE: Failure to
      understand the biosciences underpinning care has implications for safe and
      competent nursing.

PMID- 25989018
TI  - Improving patient prostate cancer risk assessment: Moving from static, globally
      applied to dynamic, practice-specific risk calculators.
AB  - Clinical risk calculators are now widely available but have generally been
      implemented in a static and one-size-fits-all fashion. The objective of this
      study was to challenge these notions and show via a case study concerning risk
      based screening for prostate cancer how calculators can be dynamically and
      locally tailored to improve on-site patient accuracy. Yearly data from five
      international prostate biopsy cohorts (3 in the US, 1 in Austria, 1 in England)
      were used to compare 6 methods for annual risk prediction: static use of the
      online US-developed Prostate Cancer Prevention Trial Risk Calculator (PCPTRC);
      recalibration of the PCPTRC; revision of the PCPTRC; building a new model each
      year using logistic regression, Bayesian prior-to-posterior updating, or random
      forests. All methods performed similarly with respect to discrimination, except
      for random forests, which were worse. All methods except for random forests
      greatly improved calibration over the static PCPTRC in all cohorts except for
      Austria, where the PCPTRC had the best calibration followed closely by
      recalibration. The case study shows that a simple annual recalibration of a
      general online risk tool for prostate cancer can improve its accuracy with
      respect to the local patient practice at hand. 

PMID- 25989020
TI  - Ebola risk perception in Germany, 2014.
AB  - Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but
      none has affected European countries like the 2014 epidemic in West Africa. We
      used an online questionnaire to investigate risk perceptions in Germany during
      this epidemic peak. Our questionnaire covered risk perceptions, knowledge about
      transmission routes, media use, reactions to the outbreak, attitudes toward
      measures to prevent the spread of EVD and vaccination against EVD, and
      willingness to volunteer for aid missions. Of 974 participants, 29% indicated
      that they worried about EVD, 4% correctly stated virus transmission routes, and
      75% incorrectly rated airborne transmission and transmission by asymptomatic
      patients as possible. Many indicated that if a patient were flown to Germany for
      treatment in a nearby hospital, they would adapt preventive behavior. Although
      most participants were not worried about EVD at the current stage of the
      epidemic, misperceptions regarding transmission were common and could trigger
      inappropriate behavior changes. 

PMID- 25989021
TI  - The pharmacokinetics of pimobendan enantiomers after oral and intravenous
      administration of racemate pimobendan formulations in healthy dogs.
AB  - Pimobendan is a benzimidazole-pyridazinone derivative, marketed as a racemic
      mixture for the management of canine heart failure. Pharmacokinetics of the
      enantiomers of pimobendan and its oral bioavailability have not been described in
      dogs. The aim of this study was to describe pharmacokinetics of three
      formulations of pimobendan in healthy dogs: the licensed capsule product, and
      novel liquid and intravenous formulations. A three-period, nested randomized two
      treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and
      i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid
      chromatography-mass spectrometry. Noncompartmental modelling was used to describe
      the pharmacokinetics. Parameters were compared between formulations using a
      general linear model. Bioequivalence of the oral formulations was tested using
      CI90 for AUC(0-infinity) and Cmax . Bioavailability of pimobendan after oral
      dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC.
      The positive enantiomer of pimobendan (PE) had a larger volume of distribution
      than the negative enantiomer (NE) (281 +/- 48 vs. 215 +/- 68 mL/kg; P = 0.003)
      and a shorter half-life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed
      more quickly than the PE into blood cells. Enantiomers of pimobendan have
      differing absorption, distribution and elimination. The pharmacokinetics of
      pimobendan in healthy dogs was described.

PMID- 25989022
TI  - Deconstructing the complexity of regulating common properties in different cell
      types: lessons from the delilah gene.
AB  - To understand development we need to understand how transcriptional regulatory
      mechanisms are employed to confer different cell types with their unique
      properties. Nonetheless it is also critical to understand how such mechanisms are
      used to confer different cell types with common cellular properties, such as the
      ability to adhere to the extracellular matrix. To decode how adhesion is
      regulated in cells stemming from different pedigrees we analyzed the regulatory
      region that drives the expression of Dei, which is a transcription factor that
      serves as a central determinant of cell adhesion, particularly by inducing
      expression of betaPS-integrin. We show that activation of dei transcription is
      mediated through multiple cis regulatory modules, each driving transcription in a
      spatially and temporally restricted fashion. Thus the dei gene provides a
      molecular platform through which cell adhesion can be regulated at the
      transcriptional level in different cellular milieus. Moreover, we show that these
      regulatory modules respond, often directly, to central regulators of cell
      identity in each of the dei-expressing cell types, such as D-Mef2 in muscle
      cells, Stripe in tendon cells and Blistered in wing intervein cells. These
      findings suggest that the acquirement of common cellular properties shared by
      different cell types is embedded within the unique differentiation program
      dictated to each of these cells by the major determinants of its identity. 

PMID- 25989023
TI  - Ezh2 maintains retinal progenitor proliferation, transcriptional integrity, and
      the timing of late differentiation.
AB  - Epigenetic regulation, including histone modification, is a critical component of
      gene regulation, although precisely how this contributes to the development of
      complex tissues such as the neural retina is still being explored. We show that
      during retinal development in mouse, there are dynamic patterns of expression of
      the polycomb repressive complex 2 (PRC2) catalytic subunit EZH2 in retinal
      progenitors and some differentiated cells, as well as dynamic changes in the
      histone modification H3K27me3. Using conditional knockout of Ezh2 using either
      Pax6-alphaCre or Six3-Cre, we find selective reduction in postnatal retinal
      progenitor proliferation, disruption of retinal lamination, and enhanced
      differentiation of several late born cell types in the early postnatal retina,
      including photoreceptors and Muller glia, which are ultimately increased in
      number and become reactive. RNA-seq identifies many non-retinal genes upregulated
      with loss of Ezh2, including multiple Hox genes and the cell cycle regulator
      Cdkn2a, which are established targets of EZH2-mediated repression. ChIP analysis
      confirms loss of the H3K27me3 modification at these loci. Similar gene
      upregulation is observed in retinal explants treated with an EZH2 chemical
      inhibitor. There is considerable overlap with EZH2-regulated genes reported in
      non-neural tissues, suggesting that EZH2 can regulate similar genes in multiple
      lineages. Our findings reveal a conserved role for EZH2 in constraining the
      expression of potent developmental regulators to maintain lineage integrity and
      retinal progenitor proliferation, as well as regulating the timing of late
      differentiation. 

PMID- 25989024
TI  - Are molecular markers useful predictors of adaptive potential?
AB  - Estimates of molecular genetic variation are often used as a cheap and simple
      surrogate for a population's adaptive potential, yet empirical evidence suggests
      they are unlikely to be a valid proxy. However, this evidence is based on
      molecular genetic variation poorly predicting estimates of adaptive potential
      rather than how well it predicts true values. As a consequence, the relationship
      has been systematically underestimated and the precision with which it could be
      measured severely overstated. By collating a large database, and using suitable
      statistical methods, we obtain a 95% upper bound of 0.26 for the proportion of
      variance in quantitative genetic variation explained by molecular diversity. The
      relationship is probably too weak to be useful, but this conclusion must be taken
      as provisional: less noisy estimates of quantitative genetic variation are
      required. In contrast, and perhaps surprisingly, current sampling strategies
      appear sufficient for characterising a population's molecular genetic variation
      at comparable markers. 

PMID- 25989026
TI  - Prevalence of hepatitis C antibodies in the population aged 16-80 years in the
      Community of Madrid 2008-2009.
AB  - Together with AIDS, the burden of hepatitis C virus (HCV) in Spain heads the list
      of communicable diseases in terms of impact on public health. The aim of this
      study was to estimate the prevalence of HCV antibodies in the Community of
      Madrid, assess changes in recent years and analyse associated risk factors.
      Descriptive cross-sectional study of a target population consisting of Community
      of Madrid residents aged 16-80 years old. Two-stage cluster sampling was
      performed, with stratification by socioeconomic status and percentage immigrant
      population. The sampling frame consisted of public blood extraction centers
      attached to the Madrid Health Service. Seroprevalence of HCV antibodies,
      prevalence ratios by age groups in comparison with 1999 survey data and
      prevalence association with risk factors were assessed using a logistic
      regression model. Prevalence of HCV antibodies for the age group 16-80 years was
      1.8% (95% CI: 1.3-2.5). The age group with the highest prevalence was 41-60
      years. In comparison with the 1999 survey, prevalence fell for the age groups 21
      30 and 31-40 years and increased for the age group 41-60. Statistically
      significant associations were found for age, education, history of hepatitis C
      and consultation regarding liver problems. Seroprevalence of HCV antibodies in
      the Community of Madrid is similar to that shown in other regions of Spain. It is
      increasing in older age groups as the population at risk ages. Incidence of
      hepatitis C may be decreasing considering the decrease in the seroprevalence in
      the population younger than 40 related to the previous serosurvey.

PMID- 25989025
TI  - Prevention of the degeneration of human dopaminergic neurons in an astrocyte co
      culture system allowing endogenous drug metabolism.
AB  - BACKGROUND AND PURPOSE: Few neuropharmacological model systems use human neurons.
      Moreover, available test systems rarely reflect functional roles of co-cultured
      glial cells. There is no human in vitro counterpart of the widely used 1-methyl-4
      phenyl-tetrahydropyridine (MPTP) mouse model of Parkinson's disease EXPERIMENTAL
      APPROACH: We generated such a model by growing an intricate network of human
      dopaminergic neurons on a dense layer of astrocytes. In these co-cultures, MPTP
      was metabolized to 1-methyl-4-phenyl-pyridinium (MPP(+) ) by the glial cells, and
      the toxic metabolite was taken up through the dopamine transporter into neurons.
      Cell viability was measured biochemically and by quantitative neurite imaging,
      siRNA techniques were also used. KEY RESULTS: We initially characterized the
      activation of PARP. As in mouse models, MPTP exposure induced (poly-ADP-ribose)
      synthesis and neurodegeneration was blocked by PARP inhibitors. Several different
      putative neuroprotectants were then compared in mono-cultures and co-cultures.
      Rho kinase inhibitors worked in both models; CEP1347, ascorbic acid or a caspase
      inhibitor protected mono-cultures from MPP(+) toxicity, but did not protect co
      cultures, when used alone or in combination. Application of GSSG prevented
      degeneration in co-cultures, but not in mono-cultures. The surprisingly different
      pharmacological profiles of the models suggest that the presence of glial cells,
      and the in situ generation of the toxic metabolite MPP(+) within the layered
      cultures played an important role in neuroprotection. CONCLUSIONS AND
      IMPLICATIONS: Our new model system is a closer model of human brain tissue than
      conventional cultures. Its use for screening of candidate neuroprotectants may
      increase the predictiveness of a test battery.

PMID- 25989029
TI  - Action observation: mirroring across our spontaneous movement tempo.
AB  - During action observation (AO), the activity of the "mirror system" is influenced
      by the viewer's expertise in the observed action. A question that remains open is
      whether the temporal aspects of the subjective motor repertoire can influence the
      "mirror system" activation. 

PMID- 25989030
TI  - Adrian Stokes and the portrait of Melanie Klein.
AB  - This paper focuses on the offer by the art writer Adrian Stokes to commission and
      pay for a portrait of the psychoanalyst Melanie Klein by the artist William
      Coldstream. It details some of the precursors of this offer in Stokes's preceding
      involvement first with Klein and then with Coldstream; her response to this
      offer; and its outcome and aftermath in Stokes's subsequent writing about Klein
      and Coldstream. 

PMID- 25989031
TI  - [Rare but important Disease: Update on ocular GvHD].

PMID- 25989032
TI  - [Allogeneic haematopoietic stem cell transplantation - an overview].
AB  - Allogeneic haematopoietic stem cell transplantation is an effective treatment
      option for chemotherapy-refractory or relapsed haematological malignancies such
      as leukaemias and lymphomas. After conditioning with chemotherapy with or without
      total body irradiation, donor cells are infused to reconstitute haematopoiesis.
      Donor-derived immune cells induce immune reactions to control or eradicate the
      underlying disease, thereby going beyond the effect of chemotherapy. This graft
      versus-tumour effect (GvT) is often accompanied by detrimental graft-versus-host
      reactions (graft-versus-host disease, GvHD), which substantially influence the
      mortality and morbidity after transplantation. The balance between GvHD and GvT,
      implementing various parameters such as donor selection, stem cell source,
      conditioning, immune reconstitution and immunosuppressive regimens, represents
      the challenge in the field of allogeneic stem cell transplantation. 

PMID- 25989033
TI  - [Clinical Signs of Ocular Graft-versus-Host Disease].
AB  - BACKGROUND: Ocular graft-versus-host disease (GvHD) is mainly an inflammatory
      ocular surface disorder after allogeneic hematopoetic stem cell transplantation
      (HSCT) with increasing incidence. METHODS: We present an overview on clinical
      signs of ocular GvHD. RESULTS: Ocular chronic GvHD representing a severe ocular
      surface disease is a long-term problem after allogeneic HSCT. It is not only
      associated with reduced quality of life because of dry eye symptoms but can also
      impair visual acuity and lead to blindness due to corneal complications. Patients
      with ocular GvHD are often resistant to therapy because of the severe dry eye
      disease and persistent inflammatory activity. CONCLUSION: A multimodal and
      interdisciplinary therapy - in cooperation with the colleagues from haematology
      and oncology is important for the treatment of patients with ocular GvHD.

PMID- 25989034
TI  - [Non-Invasive Diagnosis of Ocular Graft-versus-Host Disease].
AB  - Ocular graft-vs-host disease (GvHD) is a major complication following allogenic
      blood stem cell transplantation (aBSCT) leading to a disturbance of the ocular
      surface integrity with a broad range of severity. Leading symptom is a pronounced
      autoinflammatory reaction in particular at the ocular surface with typical
      features of dry eye disease. Potential complications include visual loss, pain
      and damage to the ocular structures with, e. g. corneal ulcerations. Diagnosis
      and treatment of ocular GvHD are a challenge for attending ophthalmologists and
      require intensive interdisciplinary patient care in particular with haemato
      oncologists. First and follow-up examinations consist of several diagnostic steps
      that include quantitative and qualitative analysis of tearfilm, visual acuity,
      ocular surface and retinal integrity, cataract development and subjective
      symptoms. Available tests are mostly evaluated for usage in dry eye diagnosis but
      are, however, mostly unspecific for diagnosing ocular GvHD reliably. Only
      combinations of several clinical tests together with the experience of
      specialised ophthalmologists may lead to the certain diagnosis and treatment
      decisions at state. This review illustrates the available established and
      innovative non-invasive diagnostic tests and evaluates their potential use for
      diagnosing ocular GvHD. 

PMID- 25989035
TI  - [Therapy for Ocular Graft-vs-Host Disease].
AB  - Therapy for ocular graft-vs-host disease (ocular GvHD) is challenging for
      ophthalmologists as progress of the disease often occurs rapidly and is
      unforeseeable. Primary goal is the preservation or restoration of visual acuity,
      however, studies on ocular GvHD that have investigated therapeutic concepts are
      limited. In contrast, most therapeutic recommendations from consensus conferences
      derive from studies on dry eye diseases other than ocular GvHD. This review
      demonstrates the available therapies in the following categories: local,
      systemic, surgical and prophylactic. Primary targets are anti-inflammation, anti
      fibrosis and lubrification of the ocular surface. In conclusion, studies strictly
      on ocular GvHD are needed to enable better evidence-based therapeutic decision
      making in the future. 

PMID- 25989036
TI  - [Patient-Centred Care of Ocular Graft-vs-Host Disease in Germany].
AB  - BACKGROUND: Ocular GvHD is a severe complication following allogenic blood stem
      cell transplantation leading to massive reduction in quality of life and ocular
      pathologies including corneal perforation. Interdisciplinary patient-centred care
      needs to be performed in specialized ophthalmic centers that provide all
      diagnostic and therapeutic options, however, only few clinics have the necessary
      infrastructure. In addition there is a lack of transparency and easily accessible
      information for the patients regarding ophthalmic care and specialized centres.
      For this reason the "Ocular GvHD working group" within the Cornea Section of the
      German Society of Ophthalmology has been founded to evaluate and improve patient
      centered care in ocular GvHD within Germany. METHODS: A survey was performed
      among the members of the Cornea Section of the German Society of Ophthalmology
      and the Directors of Departments of Ophthalmology in Germany that evaluated the
      number of annual examinations, presence of specialized GvHD outpatient clinics
      and eye screenings prior to allogenic blood stem cell transplantation (aBSCT).
      RESULTS: 25 clinics (19 university hospitals, 6 general hospitals) responded to
      the survey. In 18 clinics aBSCT are performed. Between 5 and 200 patients after
      aBSCT are examined per year per clinic. Larger institutions are associated with
      departments of haemato-oncology and other specialised disciplines to facilitate
      an interdisciplinary patient care. Three clinics are associated with GvHD
      competence centres. The major challenge in establishing an appropriate
      infrastructure for better patient-centered care is the limited or lacking
      reimbursement by health insurances. CONCLUSIONS: Within Germany only few
      ophthalmic centres exist that provide state-of-the-art patient-centered care for
      ocular GvHD. The present structures are not sufficient to treat all patients
      undergoing aBSCT following existing guidelines. Joint efforts are necessary to
      establish more and accessible competence centers for ocular GvHD with sufficient
      personnel and structural resources. In addition, ocular GvHD should be included
      as a mandatory topic in medical training and transparent and easily accessible
      information needs to be provided for patients and health-care professionals.

PMID- 25989037
TI  - [Gonioscopy - a forgotten examination method?].

PMID- 25989038
TI  - The metabolic syndrome: the future is now.

PMID- 25989039
TI  - Diversity of food-borne Bacillus volatile compounds and influence on fungal
      growth.
AB  - AIMS: To evaluate the antifungal activity of the volatile organic compounds
      (VOCs) produced by 75 different food-borne Bacillus species against Aspergillus
      niger, Aspergillus flavus, Aspergillus parasiticus, Aspergillus clavatus,
      Fusarium oxysporum f. sp. lactucae and Moniliophthora perniciosa and to determine
      the VOCs responsible for the inhibition. METHODS AND RESULTS: Bacillus strains
      inhibited fungal growth, although with different inhibition grades, with Bacillus
      subtilis, Bacillus amyloliquefaciens and Bacillus cereus strains as the best
      antifungal VOCs producers. While M. perniciosa DM4B and F. oxysporum f.sp.
      lactucae MA28 were the most sensitive fungi, A. parasiticus MG51 showed the
      greatest resistance to Bacillus VOCs exposure. Thirty-seven compounds were
      detected by SPME-GC-MS analysis, although similar patterns in volatile compounds
      were evidenced within the species, interspecific VOCs differences determined
      different effects on fungal growth. Multiple partial least regression (MPLRS) and
      antifungal activity of the individual VOCs revealed that only propanone, 1
      butanol, 3-methyl-1-butanol, acetic acid, 2-methylpropanoic acid, carbon
      disulphide, 3-methylbutanoic acid and ethyl acetate were responsible for mycelia
      inhibition of M. perniciosa DM4B and F. oxysporum f.sp. lactucae MA28.
      CONCLUSIONS: The antagonistic activity of the Bacillus VOCs was demonstrated,
      although it cannot easily be explained through the action of a single molecule,
      thus a holistic approach could be more appropriate to estimate the fungal growth
      inhibition. SIGNIFICANCE AND IMPACT OF THE STUDY: VOCs produced by Bacillus from
      cooked food can be considered as promising antifungal compounds useful in the
      control of fungal plant pathogens. This study investigates for the first time the
      correlation between mycelia inhibition of M. perniciosa and F. oxysporum f. sp.
      lactucae and the VOCs emitted by the Bacillus species.

PMID- 25989040
TI  - Influence of organic loading rate on integrated bioreactor treating hypersaline
      mustard wastewater.
AB  - Mustard tuber wastewater is characterized by high salinity and high organic
      content that is potentially detrimental to the biological treatment system and
      affects the treatment efficiency accordingly. The experiment used the integrated
      bioreactor to reduce much of the organics in mustard tuber wastewater, and found
      the influence of organic loading rate on effluent chemical oxygen demand (COD)
      and phosphate (PO4 (3-) -P). Results showed that under the condition of 10-15 
      degrees C, 6 mg/L of dissolved oxygen, the reduction value of COD removal rate in
      anaerobic and aerobic area was 14.5% and 31.7% when the organic loading rate
      increased from 2.0 to 4.0 kg COD/m(3) /day. Therefore, an integrated bioreactor
      should take 2.0 kg COD/m(3) /day organic loading rate in mustard wastewater
      treatment if the effluent is expected to meet the third level of "Integrated
      Wastewater Discharge Standard" (GB 8978-1996). 

PMID- 25989041
TI  - NCAM1-TTC12-ANKK1-DRD2 gene cluster and the clinical and genetic heterogeneity of
      adults with ADHD.
AB  - Dysfunctions of the dopaminergic system have been implicated on the etiology of
      Attention Deficit/Hyperactivity Disorder (ADHD). Meta-analyses addressing the
      association of the dopamine receptor D2 (DRD2) gene and ADHD were inconclusive
      due to excessive heterogeneity across studies. Both the great phenotypic
      heterogeneity of ADHD and the complexity of the genomic region where DRD2 is
      located could contribute to the inconsistent findings. Most previous DRD2 studies
      focused on the well-known Taq1A (rs1800497) SNP, which is actually placed in a
      neighbor gene (ANKK1). These two genes, together with NCAM1 and TTC12, form the
      NTAD gene cluster on Chr11q22-23. In order to address the reasons for the high
      heterogeneity previously reported on DRD2 effects on ADHD, this study
      investigates the role of NTAD variants on ADHD susceptibility in adults and on
      the modulation of comorbidity and personality profiles in these patients.
      Functional polymorphisms from NTAD were analyzed, both individually and in
      haplotypes, on a sample of 520 adults with ADHD and 630 non-ADHD controls. No
      direct association of NTAD variants with ADHD susceptibility itself was observed.
      However, different NTAD polymorphisms and haplotypes were associated to various
      phenotypes relevant to the clinical heterogeneity of ADHD, including Major
      Depressive Disorder, Generalized Anxiety Disorder, and Harm Avoidance and
      Persistence temperament scores. Therefore, these findings represent a possible
      explanation for the multiple conflicting findings regarding polymorphisms in this
      genomic region in psychiatry. The NTAD cluster may comprise a variety of
      independent molecular influences on various brain and behavior characteristics
      eventually associated with ADHD comorbidities and personality traits. (c) 2015
      Wiley Periodicals, Inc.

PMID- 25989043
TI  - Electrical penetration graph technique as a tool to monitor the early stages of
      aphid resistance to insecticides.
AB  - BACKGROUND: Sulfoxaflor, a new insecticide from the sulfoximine chemical family,
      and imidacloprid, a widely used neonicotinoid insecticide, were tested to assess
      the susceptibility and feeding behaviour of two populations of Myzus persicae:
      Mp61, which exhibited target-site R81T resistance to neonicotinoids, and Mp1989,
      a laboratory clone maintained since 1989 as a susceptible reference. RESULTS: The
      imidacloprid LC50 value for Mp61 was 16 times higher than for Mp1989, showing a
      moderate level of resistance. Sulfoxaflor LC50 values for Mp61 and Mp1989 were
      much closer. The probing behaviour, as assessed by electrical penetration graphs
      (EPGs), of both populations was clearly altered by sulfoxaflor, which reduced the
      ability of aphids to find and feed from the phloem. The feeding behaviour of the
      susceptible Mp1989 population was much more severely affected than the moderately
      resistant Mp61 population on imidacloprid-treated plants. PCR assays of both
      aphid populations followed by DNA sequencing identified differences between
      populations in the point mutation in the beta-subunit of the nicotinic
      acetylcholine receptor linked to the resistant gene against the neonicotinoid
      insecticide. CONCLUSIONS: Sulfoxaflor provoked feeding cessation more rapidly
      than imidacloprid in both aphid populations. Sharp differences in feeding
      behaviour were detected between the susceptible and the moderately resistant
      neonicotinoid-resistant aphid populations. The EPG technique can be used as a
      useful tool to give new insights into the functional effects of new chemical
      compounds and for early detection of low to moderate levels of resistance of sap
      feeding insects to insecticides. The potential of this technique was validated by
      molecular analysis of the R81T mutation target site.

PMID- 25989044
TI  - Pharmacological evaluation of a novel phosphodiesterase 10A inhibitor in models
      of antipsychotic activity and cognition.
AB  - In this study, we report the pharmacological effects of a novel PDE10A inhibitor,
      SEP-39. SEP-39 is a potent (1.0nM) inhibitor of human PDE10A in vitro, with good
      selectivity (>16000-fold) against other PDEs. In an in vivo occupancy study, the
      RO50 value was determined to be 0.7mg/kg (p.o.), corresponding to plasma and
      brain exposures of 28ng/mL and 43ng/g, respectively. Using microdialysis, we show
      that 3mg/kg (p.o.) SEP-39 significantly increased rat striatal cGMP
      concentrations. Furthermore, SEP-39 inhibits PCP-induced hyperlocomotion at doses
      of 1 and 3mg/kg (p.o.) corresponding to 59-86% occupancy. At similar doses in a
      catalepsy study, the time on the bar was increased but the maximal effect was
      less than that seen with haloperidol. In an EEG study, 3 and 10mg/kg (p.o.) SEP
      39 suppressed REM intensity and increased the latency to REM sleep. We also
      demonstrate the procognitive effects of SEP-39 in the rat novel object
      recognition assay. These effects appear to require less PDE10A inhibition than
      the reversal of PCP-induced hyperlocomotion or EEG effects, as improvements in
      recognition index were seen at doses of 0.3mg/kg and above. Our data demonstrate
      that SEP-39 is a potent, orally active PDE10A inhibitor with therapeutic
      potential in a number of psychiatric indications.

PMID- 25989045
TI  - Central and peripheral antinociceptive activity of 3-(2-oxopropyl)-3-hydroxy-2
      oxindoles.
AB  - Convolutamydine A has been shown to develop a significant antinociceptive effect.
      Here we demonstrated that new analogues (5-iodo-3-(2-oxopropyl)-3-hydroxy-2
      oxindole (5-Iisa), 5-fluoro-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Fisa), 5
      chloro-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Clisa) and 5-methyl-3-(2
      oxopropyl)-3-hydroxy-2-oxindole (5-Meisa)), at 0.1-10mg/kg doses, have
      significant peripheral and central antinociceptive effects in thermal and
      chemical models of nociception. Oral administered analogues demonstrated more
      pronounced antinociceptive effects than that obtained with the classical opioid
      drug morphine (5mg/kg) in the first and second phases of formalin-induced
      licking. In the tail flick model, 5-Clisa and 5-Meisa antinociceptive effect was
      almost twice as that observed with the same dose of morphine. The concomitant
      administration of diverse antagonists and the analogues indicates that 5-Iisa
      effects involve the activation of opioid pathway. On the other hand, 5-Fisa and 5
      Clisa have the participation of opioid, nitrergic, cholinergic adrenergic and
      serotoninergic pathways and 5-Meisa has the involvement of opioid, serotoninergic
      and cholinergic pathways. In conclusion, our results suggest that the new four
      analogues from Convolutamydine A have significant antinociceptive effects in
      thermal and chemical induced nociception and could be used in development of new
      drugs to be used in pain treatment with reduced side effects. 

PMID- 25989046
TI  - Antinociceptive and hypnotic activities of pregabalin in a neuropathic pain-like
      model in mice.
AB  - To evaluate the antinociceptive and hypnotic effects of pregabalin, we
      established a neuropathic pain-like model in mice using partial sciatic nerve
      ligation (PSNL), and examined thermal hyperalgesia, mechanical allodynia,
      electroencephalogram, rota-rod testing, and c-Fos expression in the anterior
      cingulate cortex. Gabapentin was used as a reference drug in the study.
      Pregabalin administered i.g. at 12.5 and 25mg/kg prolonged the duration of
      thermal latencies by 1.4- and 1.6-fold and increased the mechanical threshold by
      2.2- and 3.1-fold 3h after administration, respectively, but did not affect motor
      coordination in PSNL mice, compared with vehicle control. Pregabalin (12.5 and
      25mg/kg) given at 6:30 increased the amount of non-rapid eye movement sleep in a
      4-h period by 1.3- and 1.4-fold, respectively, in PSNL mice. However, pregabalin
      (25mg/kg) given at 20:30 did not alter the sleep pattern in normal mice.
      Immunohistochemical study showed that PSNL increased c-Fos expression in the
      neurons of anterior cingulate cortex by 2.1-fold, which could be reversed by
      pregabalin. These results indicate that pregabalin is an effective treatment for
      both neuropathic pain and sleep disturbance in PSNL mice. 

PMID- 25989047
TI  - Acute social defeat stress increases the conditioned rewarding effects of cocaine
      in adult but not in adolescent mice.
AB  - Stressful experiences modify activity in areas of the brain involved in the
      rewarding effects of psychostimulants. In the present study we evaluated the
      influence of acute social defeat (ASD) on the conditioned rewarding effects of
      cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the
      conditioned place preference (CPP) paradigm. Experimental mice were exposed to
      social defeat in an agonistic encounter before each session of conditioning with
      1mg/kg or 25mg/kg of cocaine. The effects of social defeat on corticosterone
      levels were also evaluated. Adult mice exposed to ASD showed an increase in the
      conditioned reinforcing effects of cocaine. Only these mice developed cocaine
      induced CPP with the subthreshold dose of cocaine, and they needed a higher
      number of extinction sessions for the 25mg/kg cocaine-induced CPP to be
      extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned
      reinforcing effects of cocaine, since CPP was not produced with the lower dose of
      cocaine and was extinguished faster when they were conditioned with 25mg/kg.
      Adult mice exposed to social defeat displayed higher levels of corticosterone
      than their controls and adolescent mice. Our results confirm that the effect of
      social defeat stress on the acquisition and reinstatement of the CPP induced by
      cocaine varies depending on the age at which this stress is experienced. 

PMID- 25989048
TI  - The role of purinergic and dopaminergic systems on MK-801-induced antidepressant
      effects in zebrafish.
AB  - Depression is a serious disease characterized by low mood, anhedonia, loss of
      interest in daily activities, appetite and sleep disturbances, reduced
      concentration, and psychomotor agitation. There is a growing interest in NMDA
      antagonists as a promising target for the development of new antidepressants.
      Considering that purinergic and dopaminergic systems are involved in depression
      and anxiety states, we characterized the role of these signaling pathways on MK
      801-induced antidepressant effects in zebrafish. Animals treated with MK-801 at
      the doses of 5, 10, 15, or 20MUM during 15, 30, or 60min spent longer time in the
      top area of aquariums in comparison to control group, indicating an
      anxiolytic/antidepressant effect induced by this drug. Animals treated with MK
      801 spent longer time period at top area until 2 (5MUM MK-801) and 4 (20MUM MK
      801) hours after treatment, returning to basal levels from 24h to 7days after
      exposure. Repeated MK-801 treatment did not induce cumulative effects, since
      animals treated daily during 7days had the same behavioral response pattern
      observed since the first until the 7th day. In order to investigate the effects
      of adenosine A1 and A2A receptor antagonist and agonist and the influence of
      modulation of adenosine levels on MK-801 effects, we treated zebrafish with
      caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI
      during 30min before MK-801 exposure. The non-specific adenosine receptor
      antagonist caffeine (50mg/kg) and the selective A1 receptor antagonist DPCPX
      (15mg/kg) prevented the behavioral changes induced by MK-801. The non-specific
      nucleoside transporter (NT) inhibitor dipyridamole (10mg/kg) exacerbated the
      behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride
      and SCH 23390) did not change the behavioral alterations induced by MK-801. Our
      findings demonstrated that antidepressant-like effects of MK-801 in zebrafish are
      mediated through adenosine A1 receptor activation. 

PMID- 25989050
TI  - Erratum.
AB  - Article title: "Suicide-specific Safety in the Inpatient Psychiatric Unit".
      Authors: M. L. De Santis, H. Myrick, D. A. Lamis, C. P. Pelic, C. Rhue, and J.
      York. Journal: Issues in Mental Health Nursing. Bibliometrics: Volume 36, Issue
      3, pages 190-199. DOI: 10.3109/01612840.2014.961625. The name of the fifth author
      appeared incorrectly in the online and print version of this article. The correct
      name should be:Colette Rhue. The publisher apologizes for this error.

PMID- 25989049
TI  - A high-performance white-light-emitting-diodes based on nano-single crystal
      divanadates quantum dots.
AB  - We report a high-performance phosphors-free white light-emitting-diodes (w-LEDs)
      using Ba2V2O7 or Sr2V2O7 quantum dots that directly heteroepitaxially grown on
      common quartz substrates by polymer assisted deposition (PAD). The quantum
      efficiency of quantum dots is as high as 95%. More importantly, electronic local
      functions, band structure and partial density of states have been firstly
      calculated to study the luminescent and heteroepitaxial growth mechanisms by the
      Ab-initio Simulation. Additionally, the glaring white light excited at a
      wavelength of 325 nm was experimentally observed, which unambiguously
      demonstrated that such quantum dots can be efficient w-LEDs for solid state
      lighting. 

PMID- 25989051
TI  - A eudesmane-type sesquiterpene isolated from Pluchea odorata (L.) Cass. combats
      three hallmarks of cancer cells: Unrestricted proliferation, escape from
      apoptosis and early metastatic outgrowth in vitro.
AB  - Pluchea odorata is ethno pharmaceutically used to treat inflammation-associated
      disorders. The dichloromethane extract (DME) was tested in the carrageenan
      induced rat paw oedema assay investigating its effect on inflammation that was
      inhibited by 37%. Also an in vitro anti-neoplastic potential was reported.
      However, rather limited information about the bio-activity of purified compounds
      and their cellular mechanisms are available. Therefore, two of the most abundant
      eudesmanes in P. odorata were isolated and their anti-neoplastic and anti
      intravasative activities were studied. HL-60 cells were treated with P. odorata
      compounds and metabolic activity, cell number reduction, cell cycle progression
      and apoptosis induction were correlated with relevant protein expression. Tumour
      cell intravasation through lymph endothelial monolayers was measured and
      potential causal mechanisms were analyzed by Western blotting. Compound PO-1
      decreased the metabolic activity of HL-60 cells (IC50 = 8.9 MUM after 72 h) and
      10 MUM PO-1 induced apoptosis, while PO-2 showed just weak anti-neoplastic
      activities at concentrations beyond 100 MUM. PO-1 arrested the cell cycle in G1
      and this correlated with induction of JunB expression. Independent of this
      mechanism 25 MUM PO-1 decreased MCF-7 spheroid intravasation through the lymph
      endothelial barrier. Hence, PO-1 inhibits an early step of metastasis, impairs
      unrestricted proliferation and induces apoptosis at low micromolar
      concentrations. These results warrant further testing in vivo to challenge the
      potential of PO-1 as novel lead compound.

PMID- 25989052
TI  - The genetic consequences of paternal acrylamide exposure and potential for
      amelioration.
AB  - Acrylamide is a toxin that humans are readily exposed to due to its formation in
      many carbohydrate rich foods cooked at high temperatures. Acrylamide is
      carcinogenic, neurotoxic and causes reproductive toxicity when high levels of
      exposure are reached in mice and rats. Acrylamide induced effects on fertility
      occur predominantly in males. Acrylamide exerts its reproductive toxicity via its
      metabolite glycidamide, a product which is only formed via the cytochrome P450
      detoxifying enzyme CYP2E1. Glycidamide is highly reactive and forms adducts with
      DNA. Chronic low dose acrylamide exposure in mice relevant to human exposure
      levels results in significantly increased levels of DNA damage in terms of
      glycidamide adducts in spermatocytes, the specific germ cell stage where Cyp2e1
      is expressed. Since cells in the later stages of spermatogenesis are unable to
      undergo DNA repair, and this level of acrylamide exposure causes no reduction in
      fertility, there is potential for this damage to persist until sperm maturation
      and fertilisation. Cyp2e1 is also present within epididymal cells, allowing for
      transiting spermatozoa to be exposed to glycidamide. This could have consequences
      for future generations in terms of predisposition to diseases such as cancer,
      with growing indications that paternal DNA damage can be propagated across
      multiple generations. Since glycidamide is the major contributor to DNA damage, a
      mechanism for preventing these effects is inhibiting the function of Cyp2e1.
      Resveratrol is an example of an inhibitor of Cyp2e1 which has shown success in
      reducing damage caused by acrylamide treatment in mice. 

PMID- 25989053
TI  - Ferric Ions Inhibit the Amyloid Fibrillation of beta-Lactoglobulin at High
      Temperature.
AB  - The energetics of amyloid fibrillar aggregation of beta-lactoglobulin (betaLG)
      following incubation at high temperature and acid pH was studied by differential
      scanning calorimetry in the presence of Cu(2+) or Fe(3+) cations, and without any
      metal. Cu(2+) and metal-free protein solutions showed a distinct exothermic
      response that disappeared almost completely when the Fe(3+) molar concentration
      was ten times greater than the betaLG concentration. Thioflavin T fluorescence
      studies in solution and atomic force microscopy analysis of the deposit left on
      flat mica substrates by heat-incubated betaLG solutions correlated the absence of
      exothermic response of Fe(3+)-betaLG solutions with a lack of fibril production.
      In contrast, abundant fibril deposits were observed for Cu(2+)-betaLG solutions,
      with a rich polymorphism of multistrand fibrillar structures. Electron
      paramagnetic resonance revealed that Fe(3+) permanently binds to betaLG in the
      aggregate state whereas Cu(2+) plays a catalytic role without binding to the
      protein. We propose that Fe(3+) inhibits fibril production after binding to a key
      region of the protein sequence, possibly interfering with the nucleation step of
      the fibrillation process and opening a nonfibrillar aggregation pathway. These
      findings suggest that transition metal ions can be utilized to effectively
      modulate protein self-assembly into a variety of structures with distinct
      morphologies at the nanoscale level. 

PMID- 25989054
TI  - Investigating detrusor muscle concentrations of oxybutynin after intravesical
      delivery in an ex vivo porcine model.
AB  - Intravesical oxybutynin is highly effective in the treatment of overactive
      bladder. Traditionally the mechanism of action was explained by antagonism of
      muscarinic receptors located in the detrusor, however evidence now suggests
      antimuscarinics may elicit their effect by modifying afferent pathways in the
      mucosal region. This study aimed to investigate the bladder wall distribution of
      oxybutynin in an ex vivo setting providing tissue - layer specific concentrations
      of drug achieved after intravesical delivery. Whole ex vivo porcine bladders were
      intravesically instilled with 0.167 mg mL(-1) oxybutynin solution. After 60 min,
      tissue samples were excised, serially sectioned parallel to the urothelial
      surface and extracted drug quantified. Drug distribution into the urothelium,
      lamina propria and detrusor was determined. Oxybutynin permeated into the bladder
      wall at a higher rate than other drugs previously investigated (apparent
      transurothelial Kp = 1.36 * 10(-5) cm s(-1) ). After 60 min intravesical
      instillation, concentrations achieved in the urothelium (298.69 MUg g(-1) ) and
      lamina propria (43.65 MUg g(-1) ) but not the detrusor (0.93 MUg g(-1) ) were
      greater than reported IC50 values for oxybutynin. This work adds to the
      increasing body of evidence suggesting antimuscarinics elicit their effects via
      mechanisms other than direct inhibition of detrusor contraction.

PMID- 25989055
TI  - Self-curled coral-like gamma-Al2O3 nanoplates for use as an adsorbent.
AB  - Biomimetic self-curled nanoplates assembled coral-like nanoporous gamma-Al2O3 has
      been prepared by a solvothermal method using ethylene glycol (EG)H2O as the mixed
      solvent, followed by the annealing process. The resulting samples are composed of
      micro/nanostructured units (~1.5 MUm) with self-curled porous nanoplates on the
      surface. The volume ratio of EG to water in precursor solution is crucial for the
      formation of coral-like structure. The formation process is investigated to be an
      assembly process with self-curled nanoplates driven by adsorption of EG.
      Importantly, the coral-like porous gamma-Al2O3 has high surface area of 64.18
      m(2)/g and exhibits enhanced adsorption performance for efficient removal of
      heavy metal Hg(II) (49.15 mg/g). The removal capacity is higher than (~2.5 times)
      those of commercial Al2O3 nanoparticles and hollow structured gamma-Al2O3
      prepared without EG (~2.7 times). Further investigation shows adsorption
      behaviors of the coral-like gamma-Al2O3 and the alumina hollow structure can be
      well described by Langmuir isotherm model, whereas that of commercial Al2O3
      nanoparticles fits Freundlich isotherm model. This work not only provides an
      inspiration for high efficient biomimetic adsorbent but also presents a facile
      route for coral-like gamma-Al2O3 preparation.

PMID- 25989056
TI  - Electrospray deposition in vacuum as method to create functionally active protein
      immobilization on polymeric substrates.
AB  - We demonstrate in this work the deposition of a large biological molecule
      (fibronectin) on polymeric substrates in a high vacuum environment using an
      electrospray deposition system. Fibronectin was deposited and its distribution
      and structure investigated and retention of function (ability to promote cell
      adhesion) on return to liquid environment is shown. AFM was used to monitor
      changes in the morphology of the surface before and after fibronectin deposition,
      whilst the biological activity of the deposited protein is assessed through a
      quantitative analysis of the biomolecular adhesion and migration of fibroblast
      cells to the modified surfaces. For the first time we have demonstrated that
      using high vacuum electrospray deposition it is possible to deposit large protein
      molecules on polymeric surfaces whilst maintaining the protein activity. The
      deposition of biological molecules such as proteins with the retention of their
      activity onto clean well-controlled surfaces under vacuum condition, offers the
      possibility for future studies utilizing high resolution vacuum based techniques
      at the atomic and molecular scale providing a greater understanding of protein
      surface interface behaviour of relevance to a wide range of applications such as
      in sensors, diagnostics and tissue engineering. 

PMID- 25989057
TI  - Hantzsch dihydropyridines: Privileged structures for the formation of well
      defined gold nanostars.
AB  - Anisotropic and branched gold nanoparticles have great potential in optical,
      chemical and biomedical applications. However their syntheses involve multi-step
      protocols and the use of cytotoxic agents. Here, we report a novel one-step
      method for the preparation of gold nanostructures using only Hantzsch 1,4
      dihydropyridines as mild reducing agents. The substituent pattern of the
      dihydropyridine nucleus was closely related to the ease of formation, morphology
      and stability of the nanoparticles. We observed nanostructures such as spheres,
      rods, triangles, pentagons, hexagons, flowers, stars and amorphous. We focused
      mainly on the synthesis and characterization of well-defined gold nanostars,
      which were produced quickly at room temperature (25 degrees C) in high yield and
      homogeneity. These nanostars presented an average size of 68 nm with mostly four
      or six tips. Based on our findings, we propose that the growth of the nanostars
      occurs in the (111) lattice plane due to a preferential deposition of the gold
      atoms in the early stages of particle formation. Furthermore, the nanostars were
      easily modified with peptides remaining stable for more than six months in their
      colloidal state and showing a better stability than unmodified nanostars in
      different conditions. We report a new approach using dihydropyridines for the
      straightforward synthesis of gold nanostructures with controlled shape, feasible
      for use in future applications.

PMID- 25989058
TI  - MIL-68 (In) nano-rods for the removal of Congo red dye from aqueous solution.
AB  - MIL-68 (In) nano-rods were prepared by a facile solvothermal synthesis using
      NaOAc as modulator agent at 100 degrees C for 30 min. The BET test showed that
      the specific surface area and pore volume of MIL-68 (In) nanorods were 1252 m(2)
      g(-1) and 0.80 cm(3) g(-1), respectively. The as-prepared MIL-68 (In) nanorods
      showed excellent adsorption capacity and rapid adsorption rate for removal of
      Congo red (CR) dye from water. The maximum adsorption capacity of MIL-68 (In)
      nanorods toward CR reached 1204 mg g(-1), much higher than MIL-68 (In) microrods
      and most of the previously reported adsorbents. The adsorption process of CR by
      MIL-68 (In) nano-rods was investigated and found to be obeying the Langmuir
      adsorption model in addition to pseudo-second-order rate equation. Moreover, the
      MIL-68 (In) nanorods showed an acceptable reusability after regeneration with
      ethanol. All information gives an indication that the as-prepared MIL-68 (In)
      nanorods show their potential as the adsorbent for highly efficient removal of CR
      in wastewater.

PMID- 25989059
TI  - Fitness components of Drosophila melanogaster developed on a standard laboratory
      diet or a typical natural food source.
AB  - Drosophila melanogaster is often used as a model organism in evolutionary biology
      and ecophysiology to study evolutionary processes and their physiological
      mechanisms. Diets used to feed Drosophila cultures differ between laboratories
      and are often nutritious and distinct from food sources in the natural habitat.
      Here we rear D. melanogaster on a standard diet used in our laboratory and a
      field diet composed of decomposing apples collected in the field. Flies developed
      on these two diet compositions are tested for heat, cold, desiccation, and
      starvation resistance as well as developmental time, dry body mass and fat
      percentage. The nutritional compositions of the standard and field diets were
      analyzed, and discussed in relation to the phenotypic observations. Results
      showed marked differences in phenotype of flies from the two types of diets.
      Flies reared on the field diet are more starvation resistant and they are
      smaller, leaner, and have lower heat resistance compared to flies reared on the
      standard diet. Sex specific effects of diet type are observed for several of the
      investigated traits and the strong sexual dimorphism usually observed in
      desiccation resistance in D. melanogaster disappeared when rearing the flies on
      the field diet. Based on our results we conclude that care should be taken in
      extrapolating results from one type of diet to another and especially from
      laboratory to field diets. 

PMID- 25989060
TI  - Perspectives from masters in rheumatology and autoimmunity: perspectives on the
      conventional wisdom.

PMID- 25989061
TI  - Flavones from Cassia siamea and their anti-tobacco mosaic virus activity.
AB  - Two new flavones, siameflavones A and B (1 and 2), together with five known
      flavones (3-7) were isolated from the stem of Cassia siamea. Their structures
      were elucidated by spectroscopic methods including extensive 1D and 2D NMR
      techniques. Compounds 1-5 were evaluated for their anti-tobacco mosaic virus
      (Anti-TMV) activity. The results showed that compounds 1-5 showed weak anti-TMV
      activity with inhibition rates in the range of 11.6-18.5%. 

PMID- 25989062
TI  - Risk Indicators of Papillary Recession in the Anterior Maxilla.
AB  - PURPOSE: The interdental papilla is the portion of the gingiva that occupies the
      space between two adjacent teeth. When papillary recession occurs, an array of
      problems arises ranging from phonetics to food impaction and esthetic concerns.
      The aim of this study was to identify risk indicators for visible papillary
      recession in the anterior maxilla among a Caucasian population utilizing an
      advanced analytical approach. MATERIALS AND METHODS: A dataset of 211 adult
      dentate Caucasian patients that had undergone intraoral assessment of midline
      papillary recession and extra-oral assessment of visible papillary recession
      during maximum ("Duchenne") smile was utilized. An enhanced analytical approach
      was employed to identify risk indicators for papillary recession. RESULTS:
      Approximately one-third of the participants (38%) demonstrated papillary
      recession during maximum smile ("visible papillary recession"). An association
      between sex (male preference) and visible papillary recession was found in this
      sample population, while age was found to be a risk indicator for papillary
      recession in individuals over 65 years of age. CONCLUSIONS: Visible midline
      papillary recession in the maxilla is a highly prevalent clinical entity in
      Caucasian individuals, thus the development of efficacious treatment modalities
      for papillary regeneration is necessary. Findings of the present study on risk
      indicators for visible papillary absence, namely sex and age, may facilitate
      clinicians in treating patient with compromised interdental aesthetics as well as
      identifying patients that are in high risk for loss of interdental tissues.
      CLINICAL SIGNIFICANCE: Findings of the present study on risk indicators for
      visible papillary absence, namely sex and age, indicate the need for careful
      assessment and meticulous treatment planning with respect to preservation of the
      interdental tissues. The consideration of these risk indicators can help dentists
      to identify patients at risk for papillary recession.

PMID- 25989063
TI  - Development and validation of a rapid ultra high performance liquid
      chromatography with tandem mass spectrometry method for the simultaneous
      determination of darunavir, ritonavir, and tenofovir in human plasma: Application
      to human pharmacokinetics.
AB  - A sensitive ultra high performance liquid chromatography with tandem mass
      spectrometry method was developed for the simultaneous determination of
      darunavir, ritonavir and tenofovir in human plasma. Sample preparation involved a
      simple liquid-liquid extraction using 200 MUL of human plasma extracted with
      methyl tert-butyl ether for three analytes and internal standard. The separation
      was accomplished on an Acquity UPLC BEH C18 (50 mm x 2.1 mm, 1.7 MUm) analytical
      column using gradient elution of acetonitrile/methanol (80:20, v/v) and 5.0 mM
      ammonium acetate containing 0.01% formic acid at a flow rate of 0.4 mL/min. The
      linearity of the method ranged between 20.0 and 12 000 ng/mL for darunavir, 2.0
      and 2280 ng/mL for ritonavir, and 14.0 and 1600 ng/mL for tenofovir using 200 MUL
      of plasma. The method was completely validated for its selectivity, sensitivity,
      linearity, precision and accuracy, recovery, matrix effect, stability, and
      dilution integrity. The extraction recoveries were consistent and ranged between
      79.91 and 90.04% for all three analytes and internal standard. The method
      exhibited good intra-day and inter-day precision between 1.78 and 6.27%. Finally
      the method was successfully applied for human pharmacokinetic study in eight
      healthy male volunteers after the oral administration of 600 mg darunavir along
      with 100 mg ritonavir and 100 mg tenofovir as boosters. 

PMID- 25989065
TI  - Diabetes quality of care at a university community in Beirut.
AB  - RATIONALE, AIMS AND OBJECTIVES: To assess the quality of diabetes mellitus (DM)
      care provided by a group of family doctors in Beirut. METHODS: An observational
      study, conducted at the American University of Beirut Medical Center-Family
      Medicine Clinics (AUBMC-FMC), examined the electronic health records (EHRs) of
      the beneficiaries of the Health Insurance Plan at the American University of
      Beirut (AUB-HIP) who were older than 20 years (n = 9469) in 2009. The eligible
      population included patients with DM (n = 701). Several provider/patient-directed
      interventions were introduced in the late 2000s, including a comprehensive EHRs
      system with point-of-care computer reminders, a provider financial incentive
      based on an annual performance appraisal ranked against that of the US Healthcare
      Effectiveness Data and Information Set (HEDIS) Comprehensive Diabetes Care
      indicators, as well as periodic up-to-date training. RESULTS: Optimal control for
      HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol,
      triglycerides and blood pressure were found in 58.6%, 51.0%, 22.4%, 53.3% and
      60.2% of the population, respectively. 64.1% and 70.0% received screening for
      diabetic nephropathy and a dilated eye examination, respectively. When
      benchmarked against the HEDIS Comprehensive Diabetes Care indicators, the AUB
      HIP's quality of care was 13% higher than the average of all plans in the United
      States. Screening for nephropathy, however, did not reach the above benchmark.
      CONCLUSIONS: Benchmarking served as an important tool in evaluating the current
      DM care offered and in detecting gaps, yet interventions are recommended for
      further improvement.

PMID- 25989064
TI  - Mechanisms of myoblast fusion during muscle development.
AB  - The development and regeneration of skeletal muscle require the fusion of
      mononucleated muscle cells to form multinucleated, contractile muscle fibers.
      Studies using a simple genetic model, Drosophila melanogaster, have discovered
      many evolutionarily conserved fusion-promoting factors in vivo. Recent work in
      zebrafish and mouse also identified several vertebrate-specific factors required
      for myoblast fusion. Here, we integrate progress in multiple in vivo systems and
      highlight conceptual advance in understanding how muscle cell membranes are
      brought together for fusion. We focus on the molecular machinery at the fusogenic
      synapse and present a three-step model to describe the molecular and cellular
      events leading to fusion pore formation. 

PMID- 25989066
TI  - Solution-Processed Planar Perovskite Solar Cell Without a Hole Transport Layer.
AB  - Solar cells with a structure of ITO/ZnO/CH3NH3PbI3/graphite/carbon black
      electrode were fabricated by spin coating at ambient conditions. PbI2 thin films
      were converted into CH3NH3PbI3 perovskite by reacting with CH3NH3I in solution.
      The incorporation of electrochemically exfoliated graphite improved the fill
      factor, open circuit potential and short circuit current density. The best device
      yielded 10.2% power conversion efficiency. 

PMID- 25989067
TI  - A 50-Year-Old Woman With Cowden Syndrome and Joint Pains.

PMID- 25989068
TI  - Theoretical Electronic Circular Dichroism Study of 1,3-Diene Derivatives for the
      Elucidation of ECD Spectra of 1,3-Cyclohexadiene and Its Derivatives.
AB  - The origin of P- or M-chirality of methyl substituted 1,3-cyclohexadienes are
      elucidated by time-dependent density functional theory (TD-DFT) calculation of
      1,3-cyclohexadiene derivatives and acyclic 1,3-dienes. The sign-inversion of the
      rotatory strength of the lowest excited state between 1,3-cyclohexadiene and (5R)
      axial-methyl-1,3-cyclohexadiene is caused by the conformation around the (C=)C-C(
      Me) dihedral angle. The correlation between the sign of the rotatory strength and
      conformation has been found not only in methyl substituted derivatives but also
      fluoro substituted compounds.

PMID- 25989069
TI  - Speech Perception With Combined Electric-Acoustic Stimulation: A Simulation and
      Model Comparison.
AB  - OBJECTIVE: The aim of this study is to simulate speech perception with combined
      electric-acoustic stimulation (EAS), verify the advantage of combined stimulation
      in normal-hearing (NH) subjects, and then compare it with cochlear implant (CI)
      and EAS user results from the authors' previous study. Furthermore, an automatic
      speech recognition (ASR) system was built to examine the impact of low-frequency
      information and is proposed as an applied model to study different hypotheses of
      the combined-stimulation advantage. Signal-detection-theory (SDT) models were
      applied to assess predictions of subject performance without the need to assume
      any synergistic effects. DESIGN: Speech perception was tested using a closed-set
      matrix test (Oldenburg sentence test), and its speech material was processed to
      simulate CI and EAS hearing. A total of 43 NH subjects and a customized ASR
      system were tested. CI hearing was simulated by an aurally adequate signal
      spectrum analysis and representation, the part-tone-time-pattern, which was
      vocoded at 12 center frequencies according to the MED-EL DUET speech processor.
      Residual acoustic hearing was simulated by low-pass (LP)-filtered speech with
      cutoff frequencies 200 and 500 Hz for NH subjects and in the range from 100 to
      500 Hz for the ASR system. Speech reception thresholds were determined in
      amplitude-modulated noise and in pseudocontinuous noise. Previously proposed SDT
      models were lastly applied to predict NH subject performance with EAS
      simulations. RESULTS: NH subjects tested with EAS simulations demonstrated the
      combined-stimulation advantage. Increasing the LP cutoff frequency from 200 to
      500 Hz significantly improved speech reception thresholds in both noise
      conditions. In continuous noise, CI and EAS users showed generally better
      performance than NH subjects tested with simulations. In modulated noise,
      performance was comparable except for the EAS at cutoff frequency 500 Hz where NH
      subject performance was superior. The ASR system showed similar behavior to NH
      subjects despite a positive signal-to-noise ratio shift for both noise
      conditions, while demonstrating the synergistic effect for cutoff frequencies
      >=300 Hz. One SDT model largely predicted the combined-stimulation results in
      continuous noise, while falling short of predicting performance observed in
      modulated noise. CONCLUSIONS: The presented simulation was able to demonstrate
      the combined-stimulation advantage for NH subjects as observed in EAS users. Only
      NH subjects tested with EAS simulations were able to take advantage of the gap
      listening effect, while CI and EAS user performance was consistently degraded in
      modulated noise compared with performance in continuous noise. The application of
      ASR systems seems feasible to assess the impact of different signal processing
      strategies on speech perception with CI and EAS simulations. In continuous noise,
      SDT models were largely able to predict the performance gain without assuming any
      synergistic effects, but model amendments are required to explain the gap
      listening effect in modulated noise.

PMID- 25989071
TI  - Sleep disruption is related to poor response inhibition in individuals with
      obsessive-compulsive and repetitive negative thought symptoms.
AB  - BACKGROUND AND OBJECTIVES: Obsessive-compulsive (OC) symptoms and repetitive
      negative thinking (RNT) are associated with poor inhibitory control. Sleep
      disruptions may partially mediate these relations and/or act as a "second hit" to
      individuals with OC symptoms and RNT. Models including habitual (past month)
      hours slept and bedtimes were tested. METHODS: We employed a go/no-go task that
      allowed us to examine the relation between sleep and inhibition with various task
      contingencies. Sixty-seven unselected individuals were recruited from the
      participant pool at a public university. RESULTS: Bias-corrected bootstrap
      estimates did not show that sleep disruption mediated the relation between OC
      symptoms and response inhibition nor the relation between RNT and response
      inhibition. Multiple linear regression analyses found significant interactions
      between hours slept and OC symptom severity and between RNT and hours slept to
      predict poor response inhibition. Hours slept significantly negatively predicted
      commission errors when OC symptoms and RNT levels were relatively heightened but
      not when OC symptoms and RNT levels were relatively low. These effects were
      present in blocks where task contingencies were designed to shape a no-go bias.
      No significant relations were found with habitual bedtimes. LIMITATIONS: The
      cross-sectional study design precludes testing the temporal precedence of
      symptoms in the "second hit" model. The unselected sample also limits
      generalization to clinical samples. CONCLUSIONS: These findings support a "second
      hit" model of interaction between sleep disruption and perseverative thoughts and
      behaviors. Further research on the mechanisms of the relation between sleep
      disruption and perseverative thought symptoms (OC and RNT) is warranted.

PMID- 25989072
TI  - Full correction for spatially distributed speed-of-sound in echo ultrasound based
      on measuring aberration delays via transmit beam steering.
AB  - Aberrations of the acoustic wave front, caused by spatial variations of the speed
      of-sound, are a main limiting factor to the diagnostic power of medical
      ultrasound imaging. If not accounted for, aberrations result in low resolution
      and increased side lobe level, over all reducing contrast in deep tissue imaging.
      Various techniques have been proposed for quantifying aberrations by analysing
      the arrival time of coherent echoes from so-called guide stars or beacons. In
      situations where a guide star is missing, aperture-based techniques may give
      ambiguous results. Moreover, they are conceptually focused on aberrators that can
      be approximated as a phase screen in front of the probe. We propose a novel
      technique, where the effect of aberration is detected in the reconstructed image
      as opposed to the aperture data. The varying local echo phase when changing the
      transmit beam steering angle directly reflects the varying arrival time of the
      transmit wave front. This allows sensing the angle-dependent aberration delay in
      a spatially resolved way, and thus aberration correction for a spatially
      distributed volume aberrator. In phantoms containing a cylindrical aberrator, we
      achieved location-independent diffraction-limited resolution as well as accurate
      display of echo location based on reconstructing the speed-of-sound spatially
      resolved. First successful volunteer results confirm the clinical potential of
      the proposed technique. 

PMID- 25989070
TI  - Regulation of immunoproteasome function in the lung.
AB  - Impaired immune function contributes to the development of chronic obstructive
      pulmonary disease (COPD). Disease progression is further exacerbated by pathogen
      infections due to impaired immune responses. Elimination of infected cells is
      achieved by cytotoxic CD8(+)  T cells that are activated by MHC I-mediated
      presentation of pathogen-derived antigenic peptides. The immunoproteasome, a
      specialized form of the proteasome, improves generation of antigenic peptides for
      MHC I presentation thereby facilitating anti-viral immune responses. However,
      immunoproteasome function in the lung has not been investigated in detail yet. In
      this study, we comprehensively characterized the function of immunoproteasomes in
      the human and murine lung. Parenchymal cells of the lung express low constitutive
      levels of immunoproteasomes, while they are highly and specifically expressed in
      alveolar macrophages. Immunoproteasome expression is not altered in whole lung
      tissue of COPD patients. Novel activity-based probes and native gel analysis
      revealed that immunoproteasome activities are specifically and rapidly induced by
      IFNgamma treatment in respiratory cells in vitro and by virus infection of the
      lung in mice. Our results suggest that the lung is potentially capable of
      mounting an immunoproteasome-mediated efficient adaptive immune response to
      intracellular infections. 

PMID- 25989073
TI  - Chromothripsis.

PMID- 25989074
TI  - Bat flight.

PMID- 25989075
TI  - Spectral filtering enables trichromatic vision in colorful jumping spiders.

PMID- 25989076
TI  - Cross-referencing online activity with the connectome to identify a neglected but
      well-connected neuron.

PMID- 25989077
TI  - Optogenetic control of organelle transport using a photocaged chemical inducer of
      dimerization.

PMID- 25989078
TI  - Genetics: dynamic cellular aging markers associated with major depression.
AB  - Psychiatric diseases are associated with an increased rate of somatic age-related
      illness. A new study sheds light on putative mediating cellular mechanisms by
      linking increased mitochondrial DNA copy number and decreased telomere length to
      childhood stress and major depression. 

PMID- 25989079
TI  - Plant grafting: making the right connections.
AB  - The cultivation of many crops relies on the formation of chimeric plants, where
      roots from one variety are grafted onto the shoot of another. A new study
      uncovers how two plants connect and demonstrates that the root and shoot do not
      contribute equally to the union. 

PMID- 25989080
TI  - Immunology: Dendritic Cells Pull the T Cell's Strings.
AB  - Cells communicate by sensing diffusible or surface-associated chemical signals,
      with the surface-associated molecules also providing mechanical cues. New work
      now shows that both chemical and mechanical signals are critical for the
      communication between T cells and antigen-presenting dendritic cells in the
      initiation and maintenance of immune responses.

PMID- 25989081
TI  - Neuroanatomy: connectome connects fly and mammalian brain networks.
AB  - A recent study shows that brain connectivity in Drosophila melanogaster follows a
      small-world, modular and rich-club organisation that facilitates information
      processing. This organisation shows a striking similarity with the mammalian
      brain. 

PMID- 25989082
TI  - Tumor Metabolism: MAGE-A Proteins Help TRIM Turn Over AMPK.
AB  - MAGE-A proteins are testis-specific E3 ubiquitin ligase components whose
      expression is upregulated in many cancers. MAGE-A3 and -A6 act as oncogenes and
      recent work now shows that they degrade the central metabolic regulator AMPK,
      providing a novel mechanism for rewiring cancer metabolism. 

PMID- 25989083
TI  - Human evolution: enhancing the brain.
AB  - Humans have tripled their brain size since they split from the chimpanzee
      lineage. A new paper provides for the first time functional evidence that an
      enhancer contributed to this expansion by accelerating the cell cycle in neural
      progenitors. 

PMID- 25989084
TI  - Neuron migration: anillin protects leading edge actin.
AB  - Establishment of a neuronal system requires proper regulation of the F-actin-rich
      leading edges of migrating neurons and neurite growth cones. A new study shows
      that RhoG signals through the multi-domain protein anillin to stabilize F-actin
      in these structures. 

PMID- 25989085
TI  - Human cooperation: the race to give.
AB  - An analysis of online charity donations reveals that, when males make large
      donations to attractive female fundraisers, other males respond in kind,
      providing field evidence for 'competitive altruism' in which helpful acts are
      used as a display to attract partners. 

PMID- 25989086
TI  - Plant sex chromosomes: lost genes with little compensation.
AB  - In many animals, gene loss on Y chromosomes is compensated through altered
      expression of their X-chromosome homologue. Now, however, a new study in plants
      finds that even genes deleted from the Y show no dosage compensation. 

PMID- 25989088
TI  - A Synthetic Factor XIIa Inhibitor Blocks Selectively Intrinsic Coagulation
      Initiation.
AB  - Coagulation factor XII (FXII) inhibitors are of interest for the study of the
      protease in the intrinsic coagulation pathway, for the suppression of contact
      activation in blood coagulation assays, and they have potential application in
      antithrombotic therapy. However, synthetic FXII inhibitors developed to date have
      weak binding affinity and/or poor selectivity. Herein, we developed a peptide
      macrocycle that inhibits activated FXII (FXIIa) with an inhibitory constant Ki of
      22 nM and a selectivity of >2000-fold over other proteases. Sequence and
      structure analysis revealed that one of the two macrocyclic rings of the in vitro
      evolved peptide mimics the combining loop of corn trypsin inhibitor, a natural
      protein-based inhibitor of FXIIa. The synthetic inhibitor blocked intrinsic
      coagulation initiation without affecting extrinsic coagulation. Furthermore, the
      peptide macrocycle efficiently suppressed plasma coagulation triggered by contact
      of blood with sample tubes and allowed specific investigation of tissue factor
      initiated coagulation. 

PMID- 25989087
TI  - The importance and benefits of species.
AB  - Humans depend on biodiversity in myriad ways, yet species are being rapidly lost
      due to human activities. The ecosystem services approach to conservation tries to
      establish the value that society derives from the natural world such that the
      true cost of proposed development actions becomes apparent to decision makers.
      Species are an integral component of ecosystems, and the value they provide in
      terms of services should be a standard part of ecosystem assessments. However,
      assessing the value of species is difficult and will always remain incomplete.
      Some of the most difficult species' benefits to assess are those that accrue
      unexpectedly or are wholly unanticipated. In this review, we consider recent
      examples from a wide variety of species and a diverse set of ecosystem services
      that illustrate this point and support the application of the precautionary
      principle to decisions affecting the natural world. 

PMID- 25989089
TI  - Enhancing syntrophic metabolism in up-flow anaerobic sludge blanket reactors with
      conductive carbon materials.
AB  - Syntrophic metabolism of alcohols and fatty acids is a critical step in anaerobic
      digestion, which if enhanced can better stabilize the process and enable shorter
      retention times. Direct interspecies electron transfer (DIET) has recently been
      recognized as an alternative route to hydrogen interspecies transfer as a
      mechanism for interspecies syntrophic electron exchange. Therefore, the
      possibility of accelerating syntrophic metabolism of ethanol in up-flow anaerobic
      sludge blanket (UASB) reactors by incorporating conductive materials in reactor
      design was investigated. Graphite, biochar, and carbon cloth all immediately
      enhanced methane production and COD removal. As the hydraulic retention time was
      decreased the increased effectiveness of treatment in reactors with conductive
      materials increased versus the control reactor. When these conductive materials
      were removed from the reactors rates of syntrophic metabolism declined to rates
      comparable to the control reactor. These results suggest that incorporating
      conductive materials in the design of UASB reactors may enhance digester
      effectiveness. 

PMID- 25989090
TI  - Cultivation of marine microalgae using shale gas flowback water and anaerobic
      digestion effluent as the cultivation medium.
AB  - The potential of shale gas flowback water and anaerobic digestion (AD) effluent
      to reduce the water and nutrient requirements for marine microalgae cultivation
      was evaluated with the following strains: Nannochloropsis salina, Dunaliella
      tertiolecta, and Dunaliella salina. N. salina and D. tertiolecta achieved the
      highest biomass productivity in the medium composed of flowback water and AD
      effluent (6% v/v). Growth in the above unsterilized medium was found to be
      comparable to that in sterilized commercial media with similar initial inorganic
      nitrogen concentrations, salinity, and pH levels. Specific growth rates of 0.293
      and 0.349 day(-1) and average biomass productivities of 225 and 275 mg L(-1)day(
      1) were obtained for N. salina and D. tertiolecta, respectively. The lipid
      content and fatty acid profile of both strains in the medium were also comparable
      to those obtained with commercial nutrients and salts.

PMID- 25989091
TI  - Dry anaerobic co-digestion of organic fraction of municipal waste with paperboard
      mill sludge and gelatin solid waste for enhancement of hydrogen production.
AB  - The aim of this study is to investigate the bio-H2 production via dry anaerobic
      co-fermentation of organic fraction of municipal solid waste (OFMSW) with protein
      and calcium-rich substrates such as gelatin solid waste (GSW) and paperboard mill
      sludge (PMS). Co-fermentation of OFMSW/GSW/PMS significantly enhanced the H2
      production (HP) and H2 yield (HY). The maximum HP of 1082.5+/-91.4 mL and HY of
      144.9+/-9.8 mL/gVSremoved were achieved at a volumetric ratio of 70% OFMSW:20%
      GSW:10% PMS. COD, carbohydrate, protein and lipids conversion efficiencies were
      60.9+/-4.4%, 71.4+/-3.5%, 22.6+/-2.3% and 20.5+/-1.8% respectively. Co
      fermentation process reduced the particle size distribution which is favorably
      utilized by hydrogen producing bacteria. The mean particle size diameters for
      feedstock and the digestate were 939.3 and 115.2MUm, respectively with reduction
      value of 8.15-fold in the mixtures. The volumetric H2 production increased from
      4.5+/-0.3 to 7.2+/-0.6 L(H2)/L(substrate) at increasing Ca(+2) concentrations
      from 1.8+/-0.1 to 6.3+/-0.5 g/L respectively.

PMID- 25989092
TI  - Biodegradation of nonylphenol by a novel entomopathogenic Metarhizium robertsii
      strain.
AB  - The biodegradation of nonylphenol (NP) by a newly isolated form of the larva
      fungal strain Metarhizium robertsii IM 6519 was investigated in this study. This
      isolate was capable of degrading 4-n-NP, and multiple metabolites were detected.
      The coexistence of parallel degradation pathways with versatile hydroxylation in
      different positions of the alkyl chain is a unique feature of this strain.
      Moreover, several metabolites previously described only in higher eukaryotes were
      detected in the fungal cultures. The degradation process led to the
      mineralization of 4-n-NP (with an efficiency of 36%), a great advantage of this
      strain that results in complete removal of toxic substrate from the environment. 

PMID- 25989093
TI  - Evaluation of wastewater treatment in a novel anoxic-aerobic algal-bacterial
      photobioreactor with biomass recycling through carbon and nitrogen mass balances.
AB  - Algal-bacterial symbiosis, implemented in an innovative anoxic-aerobic
      photobioreactor configuration with biomass recycling, supported an efficient
      removal of total organic carbon (86-90%), inorganic carbon (57-98%) and total
      nitrogen (68-79%) during synthetic wastewater treatment at a hydraulic and sludge
      retention times of 2 days and 20 days, respectively. The availability of
      inorganic carbon in the photobioreactor, determined by its supply in the
      wastewater and microalgae activity, governed the extent of nitrogen removal by
      assimilation or nitrification-denitrification. Unexpectedly, nitrate production
      was negligible despite the high dissolved oxygen concentrations, denitrification
      being only based on nitrite reduction. Biomass recycling resulted in the
      enrichment of rapidly settling algal flocs, which supported effluent total
      suspended solid concentrations below the European Union maximum discharge limits.
      Finally, the maximum nitrous oxide emissions recorded were far below the emission
      factors reported for wastewater treatment plants, confirming the environmental
      sustainability of this innovative photobioreactor in terms of global warming
      impact.

PMID- 25989094
TI  - Oncolytic viruses: perspectives on clinical development.
AB  - Developing a live anti-cancer agent derived in most cases from human pathogens
      presents a unique set of challenges to clinical development versus those
      anticipated with standard chemotherapeutics and small molecules. The selection of
      therapeutic targets for oncolytic virus (OV) clinical development, as is true
      with the development of any agent for cancer therapy, requires careful
      consideration beyond preclinical and early clinical data, especially when
      multiple indications may initially appear equally promising. Further, the added
      complexity of the potential for infectious complications following OV therapy
      must be anticipated in order to efficiently and safely conduct clinical studies.
      As more OV enter the clinic, these issues will become increasingly important to
      successful OV drug development. 

PMID- 25989095
TI  - Significant enhancement in photocatalytic hydrogen evolution from water using a
      MoS2 nanosheet-coated ZnO heterostructure photocatalyst.
AB  - A novel MoS2 nanosheet-coated ZnO heterostructure photocatalyst was successfully
      synthesized via a simple hydrothermal method. Two-dimensional MoS2 nanosheets
      were intimately deposited onto ZnO surface to form an intimate function, which
      favors the charge-transfer and suppresses the recombination of the photogenerated
      electron-hole pairs between MoS2 and ZnO, resulting in a significantly enhanced
      photocatalytic activity for hydrogen evolution. The photocatalytic activities of
      the MoS2-ZnO composite photocatalysts with different MoS2 contents for hydrogen
      production were systematically evaluated. The 1.00 wt% MoS2-ZnO photocatalyst
      shows the highest H2 production rate of 768 MUmol h(-1) g(-1) in the presence of
      Na2S and Na2SO3 as the sacrificial reagents, which is 14.8 times higher than that
      of pure ZnO. The photocatalytic activity of MoS2 as a cocatalyst for H2 evolution
      reaction is considerably higher than many noble metals such as Pt, Rh, Ru and Au,
      suggesting that MoS2 could act as a potential substitute for noble metals in
      photocatalytic H2 production systems. This work presents a noble-metal-free,
      highly-efficient, and stable MoS2 cocatalyst to suppress the recombination of
      electron-hole pairs of ZnO, resulting in an enhanced photocatalytic hydrogen
      production activity. 

PMID- 25989096
TI  - Geographic disparities in pancreatic cancer survival in a southeastern safety-net
      academic medical center.
AB  - OBJECTIVE: To quantify the effects of race, measures of socioeconomic status and
      geographic residency status on pancreatic cancer survival time. DESIGN:
      Retrospective review. SETTING: A southeastern safety-net academic medical centre
      in the United States. PARTICIPANTS: The study population consisted of all
      patients who were diagnosed, referred to or treated at the medical centre between
      2009 and 2012 (n = 245). To ensure completeness and accuracy of the data, follow
      up treatment and survival information about the cases were collected from the
      Georgia Comprehensive Cancer Registry in 2013. MAIN OUTCOME MEASURES: The odds of
      receiving first-course treatment (surgery, radiation or chemotherapy) and overall
      survival following a pancreatic cancer diagnosis. RESULTS: There were no observed
      differences in receipt of initial treatment; however, patients from low
      socioeconomic and rural areas had significant increase in risk of death compared
      to patients from affluent and urban areas. CONCLUSIONS: Results from this single
      site study suggests the significance of factors other than treatment differences
      that contribute to geographic disparities in mortality.

PMID- 25989097
TI  - Person-centred positive emotions, object-centred negative emotions: 2-year-olds
      generalize negative but not positive emotions across individuals.
AB  - Prior work suggests that young children do not generalize others' preferences to
      new individuals. We hypothesized (following Vaish et al., 2008, Psychol. Bull.,
      134, 383-403) that this may only hold for positive emotions, which inform the
      child about the person's attitude towards the object but not about the positivity
      of the object itself. It may not hold for negative emotions, which additionally
      inform the child about the negativity of the object itself. Two-year-old children
      saw one individual (the emoter) emoting positively or negatively towards one and
      neutrally towards a second novel object. When a second individual then requested
      an object, children generalized the emoter's negative but not her positive
      emotion to the second individual. Children thus draw different inferences from
      others' positive versus negative emotions: Whereas they view others' positive
      emotions as person centred, they may view others' negative emotions as object
      centred and thus generalizable across people. The results are discussed with
      relation to the functions and implications of the negativity bias. 

PMID- 25989098
TI  - Candida auris candidemia in Kuwait, 2014.

PMID- 25989099
TI  - Reply: To PMID 25371395.

PMID- 25989100
TI  - Response to detection of New Delhi metallo-beta-lactamase-producing bacteria,
      Brazil.

PMID- 25989101
TI  - Inhibitory effects of antiseptic mouthrinses on Streptococcus mutans,
      Streptococcus sanguinis and Lactobacillus acidophilus.
AB  - BACKGROUND: Oral antiseptics are valuable in controlling oral infections caused
      by cariogenic bacteria. The aim of this study was to investigate the effects of
      mouthrinses and pure antiseptic compounds on Streptococcus mutans and non-mutans
      bacteria (Streptococcus sanguinis and Lactobacillus acidophilus). METHODS: The
      agar diffusion assay was employed to determine bacterial growth inhibition.
      RESULTS: Commercial mouthrinses containing chlorhexidine gluconate (0.2%),
      cetylpyridinium chloride (0.05%) and sodium fluoride (0.05%) produced
      statistically similar growth inhibition of S. mutans, S. sanguinis and L.
      acidophilus (with zones of inhibition ranging from 7.56 +/- 0.52 mm to 7.39 +/-
      0.53 mm, 17.44 +/- 0.94 mm to 18.31 +/- 0.62 mm and 8.61 +/- 1.43 to 8.67 +/-
      1.43 mm respectively, p > 0.05). The chlorhexidine mouthwash produced the
      greatest mean growth inhibition of S. sanguinis and S. mutans compared to all
      other mouthrinses tested (p < 0.01). The minimum concentrations at which
      inhibition against S. mutans could be detected were chlorhexidine gluconate at
      0.005% (wt/vol), cetylpyridinium chloride 0.01% (wt/ vol), povidone iodine 10%
      (wt/vol) and sodium hypochlorite 0.5% (vol/vol). CONCLUSIONS: Chlorhexidine
      (0.01%), cetylpyridinium chloride (0.01%), povidone iodine (10%) and sodium
      hypochlorite (0.5%) are effective at inhibiting the growth of S. mutans, S.
      sanguinis and L. acidophilus.

PMID- 25989102
TI  - Palladium-Catalyzed Alkynylation of Morita-Baylis-Hillman Carbonates with
      (Triisopropylsilyl)acetylene on Water.
AB  - Direct alkynylation of Morita-Baylis-Hillman carbonates with
      (triisopropylsilyl)acetylene catalyzed by a Pd(OAc)2-NHC complex was developed
      "on water" to give the corresponding 1,4-enynes. The significant effects of water
      amount in the solvent on further transformations of 1,4-enynes were investigated.

PMID- 25989103
TI  - Patient experience measurement ignores mental health: suggestions for healthcare
      organizations.

PMID- 25989104
TI  - Thiol-disulfide exchange between the PDI family of oxidoreductases negates the
      requirement for an oxidase or reductase for each enzyme.
AB  - The formation of disulfides in proteins entering the secretory pathway is
      catalysed by the protein disulfide isomerase (PDI) family of enzymes. These
      enzymes catalyse the introduction, reduction and isomerization of disulfides. To
      function continuously they require an oxidase to reform the disulfide at their
      active site. To determine how each family member can be recycled to catalyse
      disulfide exchange, we have studied whether disulfides are transferred between
      individual PDI family members. We studied disulfide exchange either between
      purified proteins or by identifying mixed disulfide formation within cells grown
      in culture. We show that disulfide exchange occurs efficiently and reversibly
      between specific PDIs. These results have allowed us to define a hierarchy for
      members of the PDI family, in terms of ability to act as electron acceptors or
      donors during thiol-disulfide exchange reactions and indicate that there is no
      kinetic barrier to the exchange of disulfides between several PDI proteins. Such
      promiscuous disulfide exchange negates the necessity for each enzyme to be
      oxidized by Ero1 (ER oxidoreductin 1) or reduced by a reductive system. The lack
      of kinetic separation of the oxidative and reductive pathways in mammalian cells
      contrasts sharply with the equivalent systems for native disulfide formation
      within the bacterial periplasm. 

PMID- 25989105
TI  - Inhibition of ROS and inflammation by an imidazopyridine derivative X22 attenuate
      high fat diet-induced arterial injuries.
AB  - Obesity is strongly associated with the cause of structural and functional
      changes of the artery. Oxidative stress and inflammation play a critical role in
      the development of obesity-induced cardiovascular disorders. Our group previously
      found that an imidazopyridine derivative X22 showed excellent anti-inflammatory
      activity in LPS-stimulated macrophages. This study was designed to investigate
      the protective effects of X22 on high fat diet (HFD)-induced arterial injury and
      its underlying mechanisms. We observed that palmitate (PA) treatment in HUVECs
      induced a marked increase in reactive oxygen species, inflammation, apoptosis,
      and fibrosis. All of these changes were effectively suppressed by X22 treatment
      in a dose-dependent manner, associated with NF-kappaB inactivation and Nrf-2
      activation. In HFD-fed rats, administration of X22 at 10mg/kg significantly
      decreased the arterial inflammation and oxidative stress, and eventually improved
      the arterial matrix remodeling and apoptosis. X22 at 10mg/kg showed a comparable
      bioactivity with the positive control, curcumin at 50mg/kg. The in vivo
      beneficial effects of X22 are also associated with its ability to increase Nrf2
      expression and inhibit NF-kappaB activation in the artery of HFD-fed rats.
      Overall, these results suggest that X22 may have therapeutic potential in the
      treatment of obesity-induced artery injury via regulation of Nrf2-mediated
      oxidative stress and NF-kappaB-mediated inflammation. 

PMID- 25989106
TI  - Methyl-gamma-butyrobetaine decreases levels of acylcarnitines and attenuates the
      development of atherosclerosis.
AB  - OBJECTIVE: The elevation of the levels of l-carnitine and its fatty acid esters,
      acylcarnitines, in tissue or plasma has been linked to the development of
      atherosclerosis. Recently, a potent inhibitor of l-carnitine biosynthesis and
      transport, methyl-gamma-butyrobetaine (methyl-GBB), was discovered. In this
      study, we evaluated the effects of gamma-butyrobetaine (GBB), l-carnitine and
      methyl-GBB administration on the progression of atherosclerosis. METHODS:
      Apolipoprotein E knockout (apoE(-/-)) mice were treated with methyl-GBB, l
      carnitine or GBB for 4months. Following the treatment, the amount of
      atherosclerotic lesions, the number of immune cells in atherosclerotic lesions
      and the plasma lipid profile were analysed. The l-carnitine and acylcarnitine
      levels were determined in the aortic tissues of CD-1 outbred mice 2weeks after
      treatment with methyl-GBB at the dose of 10mg/kg. RESULTS: Treatment with methyl
      GBB decreased the acylcarnitine and l-carnitine levels in the aortic tissues by
      seventeen- and ten-fold, respectively. Methyl-GBB treatment at a dose of 10mg/kg
      reduced the size of atherosclerotic plaques by 36%. Neither l-carnitine nor GBB
      treatment affected the development of atherosclerosis. CONCLUSIONS: Methyl-GBB
      administration significantly attenuated the development of atherosclerosis in
      apoE(-/-)mice. Our results demonstrate that decreasing the acylcarnitine pools
      can attenuate the development of atherosclerosis.

PMID- 25989107
TI  - Exaggerated hypertensive response to combretastatin A-4 phosphate in hypertensive
      rats: Effective pharmacological inhibition by diltiazem.
AB  - Combretastatin A-4 phosphate (CA4P), a tubulin depolymerizing agent, shows
      promise in anti-cancer therapy and is associated with dose-dependent transient
      hypertension. The cardiac consequence of this hypertensive effect is unknown.
      This study was conducted to examine the cardiotoxic effect of CA4P on a rat model
      of hypertension. Hypertensive rats were created by feeding a 6% high salt (HS)
      diet to Dahl salt sensitive (DSS) rats for 2.5weeks. Cardiac toxicity was
      measured using serum troponin I levels 24h after CA4P administration. In rats fed
      HS diet, there was a significant increase in mean arterial blood pressure (MAP)
      from baseline, which was further increased by 80% following CA4P administration
      with peak systolic blood pressure (BP) of 247mmHg. Treatment with the calcium
      channel blockers, diltiazem and nicardipine, completely inhibited the
      hypertensive effects of CA4P. Nitroglycerin or enalapril, however, failed to
      completely block the hypertensive effects of CA4P. CA4P injection also
      significantly increased the cardiac troponin I level in hypertensive rats though
      pretreatment with diltiazem effectively blocked troponin I increase after CA4P
      administration. Based on these findings, an exaggerated hypertensive response to
      CA4P is associated with myocardial damage in hypertensive rats. Calcium channel
      blockers effectively blocked both CA4P induced hypertension and cardiac damage. 

PMID- 25989108
TI  - Extracellular ATP metabolism on vascular endothelial cells: A pathway with pro
      thrombotic and anti-thrombotic molecules.
AB  - Vascular endothelial contributes to the metabolism and interconversion of
      extracellular adenine nucleotides via ecto-ATPase/ADPase (CD39) and ecto
      5'nucleotidase (CD73) activities. These enzymes collectively dephosphorylate ATP,
      ADP, and AMP with the production of additional adenosine. In the vascular system,
      adenine nucleotides (ATP and ADP) and nucleoside adenosine represent an important
      class of extracellular molecules involved in modulating the processes linked to
      vascular thrombosis exerting various effects in platelets. Yet, the mechanisms by
      which the extracellular ATP metabolism in the local environment trigger pro
      thrombotic and anti-thrombotic states are yet to be fully elucidated. In this
      article, the relative contribution of extracellular ATP metabolism in platelet
      regulation is explored. 

PMID- 25989109
TI  - Peri-operative assessment of right heart function: role of echocardiography.
AB  - The right heart contributes significantly to overall cardiac function. Right
      ventricular (RV) haemodynamics and function have been defined to be
      physiologically different from the left ventricle, and yet independently
      associated with outcomes in a spectrum of conditions. In particular, RV function
      has been shown to influence prognosis of patients undergoing surgery. The
      assessment of right heart function during the intra-operative and immediate
      postoperative periods plays an important role in the clinical management of
      patients having surgery. While a number of techniques are available for the
      assessment of the right heart intra-operatively, echocardiography remains the
      prime choice being least invasive, relatively safe, readily accessible and cost
      effective. Advancements in the field of echocardiographic have improved ability
      to assess right heart function. This review examines the role echocardiography
      and advances in this imaging modality in the assessment of right heart function
      within the peri-operative setting. 

PMID- 25989110
TI  - Biobehavioral and neuroendocrine correlates of antioxidant enzyme activity in
      ovarian carcinoma.
AB  - Increased levels of reactive oxygen species (ROS) such as superoxide anions and
      hydrogen peroxide have been reported in many cancer cells and they have been
      implicated in carcinogenesis and tumor progression. Antioxidant enzymes, such as
      Manganese Superoxide Dismutase (MnSOD or SOD2) and Glutathione Peroxidase-1
      (GPx1), act coordinately to neutralize ROS. These enzymes are also thought to
      contribute to cancer cell resistance to conventional radio-chemo-therapies.
      Although some relationships have been reported between psychosocial factors and
      the regulation of antioxidant enzymes, little is known about these relationships
      in the context of cancer progression. The current study investigated the levels
      of MnSOD and GPx1in confirmed serous, high-grade tumor tissue from 60 ovarian
      cancer patients, and explored the relationship between the activity of these
      enzymes, the levels of tumor norepinephrine (NE), and patient mood as determined
      via pre-operative questionnaires. MnSOD activity was positively related to
      depressed mood (p=0.025) and tumor NE (p=0.023). In contrast, GPx1 activity was
      inversely related to fatigue (p=0.015) and tumor NE (p=0.009), and was positively
      associated with vigor (p=0.024). These findings suggest that psychological state
      and adrenergic signaling are linked with antioxidant enzyme activity in ovarian
      cancer and may have implications for patient treatments and outcomes. 

PMID- 25989112
TI  - Altered plasma fibrin clot properties in essential thrombocythemia.
AB  - Patients with increased thromboembolic risk tend to form denser fibrin clots
      which are relatively resistant to lysis. We sought to investigate whether
      essential thrombocythemia (ET) is associated with altered fibrin clot properties
      in plasma. Ex vivo plasma fibrin clot permeability coefficient (Ks), turbidimetry
      and clot lysis time (CLT) were measured in 43 consecutive patients with ET
      (platelet count from 245 to 991 * 10(3)/uL) and 50 control subjects matched for
      age, sex and comorbidities. Fibrinolysis proteins and inhibitors together with
      platelet activation markers were determined. Reduced Ks (-38%, p < 0.0001) and
      prolonged CLT (+34%, p < 0.0001) were observed in ET. The differences remained
      significant after adjustment for fibrinogen and platelet count. ET was associated
      with a slightly shorter lag phase (-5%, p = 0.01) and higher maximum absorbency
      of the turbidimetric curve (+6%, p < 0.001). The ET patients had higher plasma P
      selectin by 193% (p < 0.00001) and platelet factor 4 (PF4) by 173% (p < 0.00001),
      with higher P-selectin observed in 19 (44%) patients with JAK-2 gene V617F
      mutation. Higher t-PA (+20%, p < 0.001), 23% higher plasminogen activator
      inhibitor-1, PAI-1 (+23%, p < 0.01) and unaltered thrombin-activatable
      fibrinolysis inhibitor, plasminogen and alpha2-antiplasmin activity were found in
      the ET group. Ks inversely correlated with fibrinogen, PF4 and C-reactive
      protein. CLT positively correlated only with PAI-1. Patients with ET display
      prothrombotic plasma fibrin clot phenotype including impaired fibrinolysis, which
      represents a new prothrombotic mechanism in this disease.

PMID- 25989113
TI  - Investigation of second- and third-harmonic generation in few-layer gallium
      selenide by multiphoton microscopy.
AB  - Gallium selenide (GaSe) is a layered semiconductor and a well-known nonlinear
      optical crystal. The discovery of graphene has created a new vast research field
      focusing on two-dimensional materials. We report on the nonlinear optical
      properties of few-layer GaSe using multiphoton microscopy. Both second- and third
      harmonic generation from few-layer GaSe flakes were observed. Unexpectedly, even
      the peak at the wavelength of 390 nm, corresponding to the fourth-harmonic
      generation or the sum frequency generation from third-harmonic generation and
      pump light, was detected during the spectral measurements in thin GaSe flakes. 

PMID- 25989115
TI  - High-resolution manometry and endoscopic ultrasonography are important for
      diagnosing congenital esophageal stenosis.

PMID- 25989111
TI  - Sex-dependent modulation of age-related cognitive decline by the L-type calcium
      channel gene Cacna1c (Cav 1.2).
AB  - Increased calcium influx through L-type voltage-gated calcium channels has been
      implicated in the neuronal dysfunction underlying age-related memory declines.
      The present study aimed to test the specific role of Cacna1c (which encodes Cav
      1.2) in modulating age-related memory dysfunction. Short-term, spatial and
      contextual/emotional memory was evaluated in young and aged, wild-type as well as
      mice with one functional copy of Cacna1c (haploinsufficient), using the novel
      object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal
      expression of Cacna1c mRNA was measured by quantitative polymerase chain
      reaction. Ageing was associated with object recognition and contextual/emotional
      memory deficits, and a significant increase in hippocampal Cacna1c mRNA
      expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA
      expression in both young and old animals. However, haploinsufficient mice did not
      manifest an age-related increase in expression of this gene. Behaviourally,
      Cacna1c haploinsufficiency prevented object recognition deficits during ageing in
      both male and female mice. A significant correlation between higher Cacna1c
      levels and decreased object recognition performance was observed in both sexes.
      Also, a sex-dependent protective role of decreased Cacna1c levels in
      contextual/emotional memory loss has been observed, specifically in male mice.
      These data provide evidence for an association between increased hippocampal
      Cacna1c expression and age-related cognitive decline. Additionally, they indicate
      an interaction between the Cacna1c gene and sex in the modulation of age-related
      contextual memory declines. 

PMID- 25989114
TI  - Rethinking the pathogenesis of hepatitis B virus (HBV) infection.
AB  - Chronic hepatitis B virus (HBV) infection affects approximately 375 million
      people worldwide. Current antiviral treatment effectively controls, but rarely
      clears chronic HBV infection. In addition, a significant portion of chronic HBV
      infected patients are not suitable for currently available antiviral therapy, and
      still face higher risk for cirrhosis and hepatocellular carcinoma. The poorly
      understood pathogenesis of HBV infection is the main barrier for developing more
      effective treatment strategies. HBV has long been viewed as non-cytopathic and
      the central hypothesis for HBV pathogenesis lies in the belief that hepatitis B
      is a host specific immunity-mediated liver disease. However, this view has been
      challenged by the accumulating experimental and clinical data that support a
      model of cytopathic HBV replication. In this article we systematically review the
      pathogenic role of HBV replication in hepatitis B and suggest possible HBV
      replication related mechanisms for HBV-mediated liver injury. We propose that a
      full understanding of HBV pathogenesis should consider the following elements. I.
      Liver injury can be caused by high levels of HBV replication and accumulation of
      viral products in the infected hepatocytes. II. HBV infection can be either
      directly cytopathic, non-cytopathic, or a mix of both in an individual patient
      depending upon accumulation levels of viral products that are usually associated
      with HBV replication activity in individual infected hepatocytes.

PMID- 25989117
TI  - Vision-value-volunteering.

PMID- 25989116
TI  - Information Foraging Across the Life Span: Search and Switch in Unknown Patches.
AB  - In this study, we used a word search puzzle paradigm to investigate age
      differences in the rate of information gain (RG; i.e., word gain as a function of
      time) and the cues used to make patch-departure decisions in information
      foraging. The likelihood of patch departure increased as the profitability of the
      patch decreased generally. Both younger and older adults persisted past the point
      of optimality as defined by the marginal value theorem (Charnov, 1976), which
      assumes perfect knowledge of the foraging ecology. Nevertheless, there was
      evidence that adults were rational in terms of being sensitive to the change in
      RG for making the patch-departure decisions. However, given the limitations in
      cognitive resources and knowledge about the ecology, the estimation of RG may not
      be accurate. Younger adults were more likely to leave the puzzle as the long-term
      RG incrementally decreased, whereas older adults were more likely to leave the
      puzzle as the local RG decreased. However, older adults with better executive
      control were more likely to adjust their likelihood of patch-departure decisions
      to the long-term change in RG. Thus, age-dependent reliance on the long-term or
      local change in RG to make patch-departure decisions might be due to individual
      differences in executive control. 

PMID- 25989118
TI  - Keeping children active despite orthopaedic limitations.

PMID- 25989119
TI  - The Epidemiology of Methicillin-Resistant Staphylococcus aureus in Orthopaedics.
AB  - In the specialty of orthopaedics, methicillin-resistant Staphylococcus aureus
      (MRSA) is a major contributor to infections of the soft tissues, surgical sites,
      and joints, in addition to increasing disability, mortality, and healthcare
      costs. Inappropriate prescribing and misuse of antibiotics have led to bacterial
      resistance and the rapid emergence of MRSA. It is imperative for healthcare
      providers and facilities to improve quality, promote safety, and decrease costs
      related to MRSA infections. The healthcare profession and society as a whole play
      an important role in minimizing the transmission of pathogens, reducing the
      incidence of MRSA infections, and decreasing the development of future antibiotic
      resistant pathogens. This article discusses the epidemiology of MRSA and
      describes evidence-based guidelines pertaining to the prevention, minimization,
      and treatment of MRSA-related infections. Specific application to orthopaedics
      are discussed in the context of patient risk factors, perioperative and
      postoperative prophylaxis, and current trends regarding education and reporting
      strategies. 

PMID- 25989121
TI  - Physical activity in adolescents with an orthopaedic limitation: a review of the
      literature.
AB  - Nine out of 10 adolescents fail to achieve the Healthy People 2020 recommended
      levels of aerobic and muscle-strengthening physical activity(J. E. Fulton et al.,
      2011).Whereas all adolescents constitute a vulnerable population because of their
      minimal physical activity, those with an orthopaedic limitation, such as slipped
      capitol femoral epiphyses, are at greater risk despite sharing characteristics
      with the general adolescent population such as normal cognition and independent
      ambulation. Twenty articles are reviewed describing components of effective
      physical activity interventions for adolescents aged 10-19 and their
      applicability to the target population of those with an orthopaedic limitation.
      Although physical activity interventions for adolescents with an orthopaedic
      limitation receive limited discussion in the literature, physical capability,
      belief in ability, and nontraditional activities, including dog-walking, are
      identified as behavioral facilitators.

PMID- 25989123
TI  - Does the use of a brief cryotherapy intervention with analgesic administration
      improve pain management after total knee arthroplasty?
AB  - BACKGROUND: Prior studies have evaluated only the prolonged use of cryotherapy as
      a nonpharmacologic pain intervention. PURPOSE OF THE STUDY: The purpose of this
      study was to determine whether a 30-minute application of cryotherapy at the time
      pain medication was given after a total knee arthroplasty (TKA) provided better
      pain relief than analgesic drugs alone. METHODS: A pretest, posttest, randomized
      controlled trial study design with crossover was used to evaluate the effects of
      cryotherapy on postoperative pain and satisfaction with pain management. A
      convenience sample of postoperative knee replacement patients constituted
      participants in the study. Two sequential episodes of pain requiring analgesic
      administration were studied in each patient, one with a 30-minute cryotherapy
      application and the other without cryotherapy. Dependent variables were changes
      in pain (posttest minus pretest) and level of satisfaction with pain management.
      Data were analyzed with repeated-measures analysis of variance, with p < .05
      considered significant. RESULTS: During two sequential treatments for
      postoperative pain, a total of 29 TKA patients received analgesic medication
      administration alone for one pain episode and analgesic medication administration
      with a brief cryotherapy administration for the other pain episode. No
      significant difference between the two treatments was found for changes in pain
      scores after the treatments or patient satisfaction with pain management (p >
      .05). The order in which the treatments were provided was found to be significant
      (p = .02) for scores on patient satisfaction with pain management, with
      cryotherapy as the treatment for the second pain episode having higher scores
      than when delivered for the first pain episode. Sixty minutes after analgesic
      administration with or without cryotherapy, average pain scores remained greater
      than 7. CONCLUSION: In TKA patients, the short-term application of cryotherapy
      with analgesic medication administration did not significantly decrease pain or
      improve patient satisfaction with pain management compared with analgesic
      medication administration only. Further study is necessary to determine whether
      short-term cryotherapy shortly after TKA is of benefit to pain relief and patient
      satisfaction.

PMID- 25989124
TI  - Blisters associated with elective wrist surgery.
AB  - Blistering of the skin has been reported after high energy trauma or
      arthroplasties of large joints. It is rare in wrist trauma and seldom reported
      following elective wrist surgery. We present three cases of skin blistering after
      elective wrist surgery. Two female patients aged 18 and 35 years and one male
      patient aged 53 years were treated with total wrist fusion, carpometacarpal
      fusion, and open wrist ligament repair. They reported burning pain at the blister
      site. The blisters were clear and treated with dressing changes. There were no
      infections or wound complications and all blisters resolved without sequelae.
      These complications were probably due to a combination of factors, including
      swelling, compression from dressing and splint, multiple surgical incisions, and
      the use of adhesive dressing. Reassurance and proper wound care are recommended
      for the complication of clear blistering following elective wrist surgery. 

PMID- 25989126
TI  - Examining rheumatoid arthritis patients' trust in their provider over time: the
      effects of demographic factors and accessing sources of information.
AB  - BACKGROUND: Patients who trust their providers have better health outcomes; a
      trusting patient-provider relationship is needed for optimal management of
      rheumatoid arthritis (RA), a chronic autoimmune disease. PURPOSES/METHODS: An
      observational study design (N = 100 RA patients) was used to: RESULTS: :
      Patients' trust in their providers decreased over time. Less-educated persons and
      those who accessed information from the Internet reported less trust in their
      providers. Patients who consulted a larger number of information sources rated
      trust in their provider more positively. CONCLUSION: RA patients' trust in
      providers is a dynamic construct influenced by education and health information.

PMID- 25989127
TI  - Acetaminophen by infusion.
AB  - Acetaminophen is a nonsteroidal, nonsalicylate analgesic and antipyretic that is,
      today, the most common medication ingredient found in oral and rectal over-the
      counter and prescription drugs. However, it was not until 2010 that Ofirmev
      (acetaminophen), an injection form of acetaminophen, was approved for treating
      mild to moderate pain, as an adjunct to opioids for severe pain, and reduction of
      fever in those younger than 2 years. Thus, intravenous acetaminophen may be
      appropriately used in a wide variety of settings and nurses who are knowledgeable
      and informed about the correct use of intravenous acetaminophen will be able to
      reduce the potential for medication misadventures. In this article, the uses and
      cautions for Ofirmev are discussed. 

PMID- 25989130
TI  - The DNP and the 2015 AACN Mandate.

PMID- 25989132
TI  - PCSK9 inhibitors: Novel therapeutic agents for the treatment of
      hypercholesterolemia.
AB  - Reducing plasma levels of low-density lipoprotein cholesterol (LDL-c) remains the
      cornerstone in the primary and secondary prevention of cardiovascular disease.
      However, a substantial proportion of patients fail to achieve acceptable LDL-c
      levels with currently available lipid-lowering drugs. Over the last decade,
      inhibition of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has emerged
      as a promising target to reduce residual cardiovascular disease risk. Binding of
      PCSK9 to the LDL receptor targets the LDL receptor for lysosomal degradation.
      Inhibition of PCSK9 increases expression of the LDL receptor. This observation
      has led to the development of a number of approaches to directly target PCSK9.
      Three monoclonal antibodies against PCSK9 are currently being evaluated in phase
      3 trials involving various patient categories on different background lipid
      lowering therapies. Current evidence shows reductions in LDL cholesterol levels
      of up to 70%, independent of background statin therapy. The results of phase 3
      trials will demonstrate the long-term efficacy and safety of PCSK9 inhibition,
      and will indicate whether LDL-c lowering induced by this novel approach
      translates into beneficial effects on CVD outcome. 

PMID- 25989133
TI  - Innovative pharmaceutical interventions in cardiovascular disease: Focusing on
      the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raising: A systematic
      review and meta-analysis of relevant preclinical studies and clinical trials.
AB  - Non-HDL-cholesterol is well recognised as a primary causal risk factor in
      cardiovascular disease. However, despite consistent epidemiological evidence for
      an inverse association between HDL-C and coronary heart disease, clinical trials
      aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their
      primary goals. This systematic review and meta-analysis investigated the effects
      of established and novel treatment strategies, specifically targeting HDL, on
      inhibition of atherosclerosis in cholesteryl ester transfer protein-expressing
      animals, and the prevention of clinical events in randomised controlled trials.
      Linear regression analyses using data from preclinical studies revealed
      associations for TC and non-HDL-C and lesion area (R(2)=0.258, P=0.045;
      R(2)=0.760, P<0.001), but not for HDL-C (R(2)=0.030, P=0.556). In clinical
      trials, non-fatal myocardial infarction risk was significantly less in the
      treatment group with pooled odd ratios of 0.87 [0.81; 0.94] for all trials and
      0.85 [0.78; 0.93] after excluding some trials due to off-target adverse events,
      whereas all-cause mortality was not affected (OR 1.05 [0.99-1.10]). Meta
      regression analyses revealed a trend towards an association between between-group
      differences in absolute change from baseline in LDL-C and non-fatal myocardial
      infarction (P=0.066), whereas no correlation was found for HDL-C (P=0.955). We
      conclude that the protective role of lowering LDL-C and non-HDL-C is well
      established. The contribution of raising HDL-C on inhibition of atherosclerosis
      and the prevention of cardiovascular disease remains undefined and may be
      dependent on the mode of action of HDL-C-modification. Nonetheless, treatment
      strategies aimed at improving HDL function and raising apolipoprotein A-I may be
      worth exploring. 

PMID- 25989134
TI  - Assessing the stereoselectivity of carbonyl reductases toward the reduction of
      OPBE and docking analysis.
AB  - The asymmetric reduction of prochiral carbonyl compounds by NAD(P)H-dependent
      carbonyl reductases represents a powerful method for the production of optically
      active alcohols. The stereoselectivity of a series of carbonyl reductases were
      evaluated toward the reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). A majority
      of reductases produced the ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE) with
      low to excellent enantiomeric excess (e.e.), whereas about 30% reductases
      catalyzed OPBE to form (S)-HPBE. Among them, the carbonyl reductase from
      Saccharomyces cerevisiae (SeCR) and short-chain dehydrogenase from Gluconobacter
      oxydans (GoKR) exhibited 100% e.e., yielding the corresponding (R) and (S)-HPBE,
      respectively. However, the SeCR showed relative higher activity (29.0 U/mg) and
      affinity (Km of 0.22 mM) than those of GoKR. Docking analysis found that the
      interaction of OPBE with enzyme-NADPH complex determined the NADPH-provided
      hydrogen transfer and the configuration of reductive product. These results
      indicated that the three-dimensional (3D) structure of enzymes controlled the
      stereoselectivity of the reductive product based on the geometry of the substrate
      and cofactor. 

PMID- 25989135
TI  - Can poisons stimulate bees? Appreciating the potential of hormesis in bee
      pesticide research.
AB  - Hormesis, a biphasic dose response whereby exposure to low doses of a stressor
      can stimulate biological processes, has been reported in many organisms,
      including pest insects when they are exposed to low doses of a pesticide.
      However, awareness of the hormesis phenomenon seems to be limited among bee
      researchers, in spite of the increased emphasis of late on pollinator toxicology
      and risk assessment. In this commentary, we show that there are several examples
      in the literature of substances that are toxic to bees at high doses but
      stimulatory at low doses. Appreciation of the hormetic dose response by bee
      researchers will improve our fundamental understanding of how bees respond to low
      doses of chemical stressors, and may be useful in pollinator risk assessment.

PMID- 25989138
TI  - Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and
      gastrointestinal tract of calves after subcutaneous injection, and bactericidal
      impacts on representative enteric bacteria.
AB  - This study's objectives were to determine intestinal antimicrobial concentrations
      in calves administered enrofloxacin or ceftiofur sodium subcutaneously, and their
      impact on representative enteric bacteria. Ultrafiltration devices were implanted
      in the ileum and colon of 12 steers, which received either enrofloxacin or
      ceftiofur sodium. Samples were collected over 48 h after drug administration for
      pharmacokinetic/pharmacodynamic analysis. Enterococcus faecalis or Salmonella
      enterica (5 * 10(5) CFU/mL of each) were exposed in vitro to peak and tail (48 h
      postadministration) concentrations of both drugs at each location for 24 h to
      determine inhibition of growth and change in MIC. Enrofloxacin had tissue
      penetration factors of 1.6 and 2.5 in the ileum and colon, while ciprofloxacin,
      an active metabolite of enrofloxacin, was less able to cross into the intestine
      (tissue penetration factors of 0.7 and 1.7). Ceftiofur was rapidly eliminated
      leading to tissue penetration factors of 0.39 and 0.25. All concentrations of
      enrofloxacin were bactericidal for S. enterica and significantly reduced E.
      faecalis. Peak ceftiofur concentration was bactericidal for S. enterica, and tail
      concentrations significantly reduced growth. E. faecalis experienced growth at
      all ceftiofur concentrations. The MICs for both organisms exposed to peak and
      tail concentrations of antimicrobials were unchanged at the end of the study.
      Enrofloxacin and ceftiofur achieved intestinal concentrations capable of reducing
      intestinal bacteria, yet the short exposure of ceftiofur in the intestine may
      select for resistant organisms.

PMID- 25989136
TI  - IL-1beta reduces tonic contraction of mesenteric lymphatic muscle cells, with the
      involvement of cycloxygenase-2 and prostaglandin E2.
AB  - BACKGROUND AND PURPOSE: The lymphatic system maintains tissue homeostasis by
      unidirectional lymph flow, maintained by tonic and phasic contractions within
      subunits, 'lymphangions'. Here we have studied the effects of the inflammatory
      cytokine IL-1beta on tonic contraction of rat mesenteric lymphatic muscle cells
      (RMLMC). EXPERIMENTAL APPROACH: We measured IL-1beta in colon-conditioned media
      (CM) from acute (AC-CM, dextran sodium sulfate) and chronic (CC-CM, T-cell
      transfer) colitis-induced mice and corresponding controls (Con-AC/CC-CM). We
      examined tonic contractility of RMLMC in response to CM, the cytokines h-IL-1beta
      or h-TNF-alpha (5, 10, 20 ng.mL(-1) ), with or without COX inhibitors [TFAP (10(
      5)  M), diclofenac (0.2 * 10(-5)  M)], PGE2 (10(-5)  M)], IL-1-receptor
      antagonist, Anakinra (5 MUg.mL(-1) ), or a selective prostanoid EP4 receptor
      antagonist, GW627368X (10(-6) and 10(-7)  M). KEY RESULTS: Tonic contractility of
      RMLMC was reduced by AC- and CC-CM compared with corresponding control culture
      media, Con-AC/CC-CM. IL-1beta or TNF-alpha was not found in Con-AC/CC-CM, but
      detected in AC- and CC-CM. h-IL-1beta concentration-dependently decreased RMLMC
      contractility, whereas h-TNF-alpha showed no effect. Anakinra blocked h-IL-1beta
      induced RMLMC relaxation, and with AC-CM, restored contractility to RMLMC. IL
      1beta increased COX-2 protein and PGE2 production in RMLMC.. PGE2 induced
      relaxations in RMLMC, comparable to h-IL-1beta. Conversely, COX-2 and EP4
      receptor inhibition reversed relaxation induced by IL-1beta. CONCLUSIONS AND
      IMPLICATIONS: The IL-1beta-induced decrease in RMLMC tonic contraction was COX-2
      dependent, and mediated by PGE2 . In experimental colitis, IL-1beta and tonic
      lymphatic contractility were causally related, as this cytokine was critical for
      the relaxation induced by AC-CM and pharmacological blockade of IL-1beta restored
      tonic contraction.

PMID- 25989139
TI  - Social support and the serotonin transporter genotype (5-HTTLPR) moderate levels
      of resilience, sense of coherence, and depression.
AB  - Gene x environment interactions have mainly been investigated in models of
      psychopathology. However, the putative interplay between genes and beneficial
      environmental conditions on positive outcomes has rarely been addressed. We
      therefore examined the interaction between the serotonin transporter linked
      polymorphic region (5-HTTLPR) and social support on the sense of coherence (SOC),
      resilience, and depressive symptoms. Furthermore, we scrutinized our examinations
      by differentiating between individuals with and without childhood abuse. The
      sample included 1,811 participants from the general population (Study of Health
      in Pomerania, Germany). The triallelic genotype of 5-HTTLPR was determined and
      longitudinal data of social support were used. Among individuals with high social
      support no significant differences between 5-HTTLPR genotypes regarding all
      outcome variables were found. However, among those with low social support,
      carriers of at least one short allele reported significantly increased levels of
      SOC and resilience, as well as less depressive symptoms than carriers of the l/l
      genotype. This result was not modified by differentiating between those with
      childhood abuse and those without. In less supportive social environments the
      impact of distinct genotypes on behavioral outcomes might be more relevant than
      in supportive environments where social compensation might take place. Our
      findings indicate that both alleles of 5-HTTLPR contribute to the adaptability to
      different environmental conditions.

PMID- 25989140
TI  - Triplex real-time PCR--an improved method to detect a wide spectrum of
      mitochondrial DNA deletions in single cells.
AB  - Mitochondrial DNA (mtDNA) mutations are commonly found in the skeletal muscle of
      patients with mitochondrial disease, inflammatory myopathies and sarcopenia. The
      majority of these mutations are mtDNA deletions, which accumulate to high levels
      in individual muscle fibres causing a respiratory defect. Most mtDNA deletions
      are major arc deletions with breakpoints located between the origin of light
      strand (OL) and heavy strand (OH) replication within the major arc. However,
      under certain disease conditions, rarer, minor arc deletions are detected.
      Currently, there are few techniques which would allow the detection and
      quantification of both types of mtDNA deletions in single muscle fibres. We have
      designed a novel triplex real-time PCR assay which simultaneously amplifies the
      MT-ND4 gene in the major arc, the MT-ND1 gene in the minor arc, and the non
      coding D-Loop region. We demonstrate that this assay is a highly sensitive and
      reliable tool for the detection and quantification of a broad range of major and
      minor arc mtDNA deletions with the potential to investigate the molecular
      pathogenesis in both research and diagnostic settings. 

PMID- 25989141
TI  - Neurocognitive dysfunction and pharmacological intervention using guanfacine in a
      rhesus macaque model of self-injurious behavior.
AB  - Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders
      but there is a dearth of information about neurological mechanisms underlying the
      behavior, and few animal models exist. SIB in humans is characterized by any
      intentional self-directed behavior that leads to wounds, whereas in macaques it
      is not always accompanied by wounds. We describe a cohort of rhesus macaques
      displaying SIB as adults, in which changes within the central nervous system were
      associated with the SIB. In these macaques, increases in central nervous system
      striatal dopamine (DA) receptor binding (BPND) measured by positron emission
      tomography (PET) [11C]raclopride imaging correlated with severity of wounding
      (rs=0.662, P=0.014). Furthermore, utilizing standardized cognitive function
      tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits
      in attentional set shifting (intra-/extradimensional shift) were correlated with
      increased severity of SIB (rs=0.563, P=0.045 and rs=0.692, P=0.009,
      respectively). We also tested the efficacy of guanfacine, an alpha2A adrenergic
      agonist that acts to improve postsynaptic transmission of neuronal impulses, in
      reducing SIB. A subset of these animals were enrolled in a randomized
      experimenter-blinded study that demonstrated guanfacine decreased the severity of
      wounding in treated animals compared with vehicle-only-treated controls
      (P=0.043), with residual beneficial effects seen for several weeks after
      cessation of therapy. Animals with the highest severity of SIB that received
      guanfacine also showed the most significant improvement (rs=-0.761, P=0.009). The
      elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have
      been improved by guanfacine. With underlying physiology potentially
      representative of the human condition and the ability to affect outcome measures
      of disease using pharmacotherapy, this model represents a unique opportunity to
      further our understanding of the biology and treatment of SIB in both animals and
      humans. 

PMID- 25989142
TI  - The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8)
      regulates noncoding RNAs and autism-related genes.
AB  - Chromodomain helicase DNA-binding protein 8 (CHD8) was identified as a leading
      autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and
      subsequent targeted-sequencing studies. De novo loss-of-function mutations were
      identified in 12 individuals with ASD and zero controls, accounting for a highly
      significant association. Small interfering RNA-mediated knockdown of CHD8 in
      human neural progenitor cells followed by RNA sequencing revealed that CHD8
      insufficiency results in altered expression of 1715  genes, including both
      protein-coding and noncoding RNAs. Among the 10 most changed transcripts, 4 (40%)
      were noncoding RNAs. The transcriptional changes among protein-coding genes
      involved a highly interconnected network of genes that are enriched in neuronal
      development and in previously identified ASD candidate genes. These results
      suggest that CHD8 insufficiency may be a central hub in neuronal development and
      ASD risk. 

PMID- 25989144
TI  - Analysis of Diffusion-Controlled Dissolution from Polydisperse Collections of
      Drug Particles with an Assessed Mathematical Model.
AB  - We introduce a "hierarchical" modeling strategy designed to be systematically
      extensible to increase the detail of dissolution predictions from polydisperse
      collections of drug particles and to be placed on firm mathematical and physical
      foundations with diffusion-dominated dissolution at its core to predict
      dissolution and the evolution of particle size distribution. We assess the model
      with experimental data and demonstrate higher accuracy by treating the
      polydisperse nature of dissolution. A level in the hierarchy is applied to study
      elements of diffusion-driven dissolution, in particular the role of particle-size
      distribution width with varying dose level and the influences of "confinement" on
      the process of dissolution. Confinement influences surface molecular flux,
      directly by the increase in bulk concentration and indirectly by the relative
      volume of particles to container. We find that the dissolution process can be
      broadly categorized within three "regimes" defined by the ratio of total
      concentration Ctot to solubility CS . Sink conditions apply in the first regime,
      when C tot /CS<~0.1. When C tot /CS>~5 (regime 3) dissolution is dominated by
      confinement and normalized saturation time follows a simple power law
      relationship. Regime 2 is characterized by a "saturation singularity" where
      dissolution is sensitive to both initial particle size distribution and
      confinement.

PMID- 25989143
TI  - Altered functional brain network connectivity and glutamate system function in
      transgenic mice expressing truncated Disrupted-in-Schizophrenia 1.
AB  - Considerable evidence implicates DISC1 as a susceptibility gene for multiple
      psychiatric diseases. DISC1 has been intensively studied at the molecular,
      cellular and behavioral level, but its role in regulating brain connectivity and
      brain network function remains unknown. Here, we utilize a set of complementary
      approaches to assess the functional brain network abnormalities present in mice
      expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice
      exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus
      along with a reorganization of functional brain network connectivity that
      included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC
      connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis,
      with Disc1tr Hemi mice showing a reduced probability of presynaptic
      neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC
      projection. Glutamate system dysfunction in Disc1tr Hemi mice was further
      supported by the attenuated cerebral metabolic response to the NMDA receptor
      (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR
      subunits 2A and 2B in these animals. These data show that the Disc1 truncation in
      Disc1tr Hemi mice induces a range of translationally relevant endophenotypes
      underpinned by glutamate system dysfunction and altered brain connectivity. 

PMID- 25989145
TI  - Acute middle East respiratory syndrome coronavirus infection in livestock
      Dromedaries, Dubai, 2014.
AB  - Camels carry Middle East respiratory syndrome coronavirus, but little is known
      about infection age or prevalence. We studied >800 dromedaries of all ages and 15
      mother-calf pairs. This syndrome constitutes an acute, epidemic, and time-limited
      infection in camels <4 years of age, particularly calves. Delayed social
      separation of calves might reduce human infection risk. 

PMID- 25989146
TI  - Corrosion resistance of Ti modified by chitosan-gold nanoparticles for orthopedic
      implantation.
AB  - Highly uniform bionanocomposite film composed of chitosan (CS) and gold
      nanoparticles (AuNPs) was synthesized successfully by electrodeposition method.
      The influence of AuNPs/CS bionanocomposite film on corrosion resistance of Ti was
      investigated. Surface morphology and compositional properties of the
      bionanocomposite were analyzed by scanning electron microscope (SEM), energy
      dispersive X-ray analysis (EDX), and X-ray photoelectron spectroscopy (XPS).
      Moreover, cyclic voltammetry (CV), open-circuit potential measurements (OCP),
      electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization
      (Rp) were used to examine the corrosion behavior in Hanks' solution. In
      comparison with Ti, Nyquist and Bode plots displayed higher impedance values and
      phase angles for AuNPs/CS biocomposite denoting a more protective passive film on
      Ti with inhibition efficiency (IE%) of 98%. An electric equivalent circuit with
      three time constants was modeled for the bionanocomposite. In addition, the
      antibacterial effect revealed the high efficiencies of the bionanocomposite film
      for inhibiting bacterial growth. The combination of the high biocompatibility of
      chitosan and strong adsorption ability of AuNPs make AuNPs/CS bionanocomposite
      promising candidate for modifying biomaterial surfaces for medical implantation
      applications. 

PMID- 25989147
TI  - Biosurfactant produced from Actinomycetes nocardiopsis A17: Characterization and
      its biological evaluation.
AB  - This investigation aims to isolate an Actinomycetes strain producing a
      biosurfactant from the unexplored region of industrial and coal mine areas.
      Actinomycetes are selected for this study as their novel chemistry was not
      exhausted and they have tremendous potential to produce bioactive secondary
      metabolites. The biosurfactant was characterized and further needed to be
      utilized for pharmaceutical dosage form. Isolation, purification, screening, and
      characterization of the Actinomycetes A17 were done followed by its fermentation
      in optimized conditions. The cell-free supernatant was used for the extraction of
      the biosurfactant and precipitated by cold acetone. The dried precipitate was
      purified by TLC and the emulsification index, surface tension and CMC were
      determined. The isolated strain with preferred results was identified as
      Actinomycetes nocardiopsis A17 with high foam-forming properties. It gives
      lipase, amylase, gelatinase, and protease activity. The emulsification index was
      found to be 93+/-0.8 with surface tension 66.67 dyne/cm at the lowest
      concentration and cmc 0.6 MUg/ml. These biosurfactants were characterized by
      Fourier transform infra red (FT-IR) spectroscopy and liquid chromatography-mass
      spectrometry (LC-MS). Therefore, it can be concluded that the biosurfactant
      produced by Actinomycetes nocardiopsis sp. strain A17 was found to have
      satisfactory results with high surface activity and emulsion-forming ability.

PMID- 25989148
TI  - The effects of sugars on moisture sorption isotherm and functional properties of
      cold water fish gelatin films.
AB  - Sugars were incorporated into CWFG solutions at different ratios (0%, 2%, 4%, and
      6% w/w). Functional properties of the modified films were characterized following
      American standard test methods, and moisture sorption isotherm was characterized
      by polynomial and GAB models. Permeation to water vapor and oxygen of the
      modified films decreased compared to that of the control CWFG films. Moisture
      content, solubility, and monolayer water content of CWFG films decreased with the
      increase of sugar content. The addition of sugars significantly increased the
      Tensile strength of CWFG films from 30 to 40 MPa for ribose, and 30 to 35 MPa for
      fructose whereas elongation at the breaks decreased from 60% to 30% for ribose,
      and from 60% to 45% for that which incorporated fructose sugars. Moisture
      sorption isotherm curve significantly shifted to lower moisture content in
      aw<0.6. In aw>0.6, ribose-incorporated CWFG films, had similar function to
      hydrogel materials. In all the characterizations, the effects of ribose were
      significantly higher than those of fructose. Results of this research can be
      explored for commercial use, depending on the application for either packaging
      purposes or in the cosmetics industries.

PMID- 25989149
TI  - Design, synthesis, and anti-inflammatory evaluation of novel diphenylthiazole
      thiazolidinone hybrids.
AB  - A series of diphenylthiazole-thiazolidinone hybrids was synthesized and evaluated
      in vitro and in vivo as anti-inflammatory/analgesic agents. The inhibition of
      cyclooxygenase (COX) enzymes was suggested as a molecular mechanism for the
      hybrids to exert their anti-inflammatory action. Of these compounds, 13b, 14, and
      15b showed the most potent COX inhibitory activity with IC50 values between 2.03
      and 12.27 uM, but with different selectivity profiles. All compounds were further
      evaluated in vivo for their anti-inflammatory/analgesic activities using three
      animal models. Interestingly, the results of the COX assay were in agreement with
      those of in vivo assays where the most potent COX inhibitors, 13b, 14, and 15b,
      exhibited the highest anti-inflammatory/analgesic activities compared to
      diclofenac. On the contrary, compounds 11 and 12 were the least potent ligands in
      vitro and in vivo as well. 

PMID- 25989150
TI  - Obituary for Robert Wallerstein (1921-2014).

PMID- 25989151
TI  - A new cyclolignan glycoside from the tubers of Pinellia ternata.
AB  - A new 2,7'-type cyclolignan glycoside, cyclolignanyingoside A (1), together with
      six known compounds (2-7) were isolated from the tubers of Pinellia ternata
      (Thunb.) Breit. The structure of 1 was elucidated on the basis of chemical and
      spectral analysis, including 1D, 2D NMR analyses, HR-ESI-MS, and CD spectrometry.
      The cytotoxic, antioxidant and tyrosinase-inhibiting activities of all the
      isolates were determined. However, all the isolates exhibited no activity on the
      selected cell lines (Hep-3B, Bcap-37, and MCF-7). In addition, compounds 1-3 and
      7 exhibited strong 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) free
      radical scavenging activity, and compounds 2 and 4 showed a moderate mushroom
      tyrsinase inhibitory activity. 

PMID- 25989152
TI  - Deciphering beta-Lactoglobulin Interactions at an Oil-Water Interface: A
      Molecular Dynamics Study.
AB  - Protein adsorption at liquid-liquid interfaces is of immense relevance to many
      biological processes and dairy-based functional foods. Due to experimental
      limitations, however, there is still a remarkable lack of understanding of the
      adsorption mechanism, particularly at a molecular level. In this study, atomistic
      molecular dynamics simulations were used to elucidate the approach and adsorption
      mechanism of beta-lactoglobulin (beta-LG) at a decane-water interface. Through
      multiple independent simulations starting from three representative initial
      orientations of beta-LG relative to the decane surface the rate at which beta-LG
      approaches the oil/water interface is found to be independent of its initial
      orientation, and largely stochastic in nature. While the residues that first make
      contact with the decane and the final orientation of beta-LG upon adsorption are
      similar in all cases, the adsorption process is driven predominantly by
      structural rearrangements that preserve the secondary structure but expose
      hydrophobic residues to the decane surface. This detailed characterization of the
      adsorption of beta-LG at an oil/water interface should inform the design and
      development of novel encapsulation and delivery systems in the food and
      pharmaceutical sciences. 

PMID- 25989153
TI  - Number of Circulating Follicular Helper 2 T Cells Correlates With IgG4 and
      Interleukin-4 Levels and Plasmablast Numbers in IgG4-Related Disease.
AB  - OBJECTIVE: To elucidate the pathologic role of follicular helper T (Tfh) cells
      and their subsets in active, untreated IgG4-related disease. METHODS: Fifteen
      patients with active, untreated, biopsy-proven IgG4-related disease, 24 patients
      with primary Sjogren's syndrome (SS), 12 patients with allergic rhinitis, and 23
      healthy controls were evaluated. Tfh cells were defined as CD3+CD4+CXCR5+CD45RA-
      cells. Circulating Tfh cell subsets among CXCR5+CD45RA-CD4+ T cells were defined
      as Tfh17 cells (CXCR3-CCR6+), Tfh1 cells (CXCR3+CCR6-), or Tfh2 cells (CXCR3-CCR6
      ). CD19+CD20-CD27+CD38+ cells were defined as plasmablasts. Serum cytokine levels
      (interleukin-4 [IL-4], IL-10, IL-21, and IL-33) were measured by cytometric bead
      array or enzyme-linked immunosorbent assay. RESULTS: Patients with IgG4-related
      disease had significantly increased levels of Tfh2 cells compared to healthy
      controls or patients with primary SS or allergic rhinitis. Increased Tfh2 levels
      were strongly associated with increased serum IgG4 levels and the IgG4:IgG ratio
      in IgG4-related disease. A positive correlation was observed between Tfh2 counts,
      plasmablast counts, and serum IL-4 levels. Interestingly, levels of plasmablasts
      and serum IL-4 and IgG4 decreased after treatment with glucocorticoids, whereas
      no obvious change was observed in Tfh2 cell counts. CONCLUSION: The Tfh2 cell
      count was specifically increased in IgG4-related disease and was correlated with
      elevated serum levels of IgG4 and IL-4 and plasmablast counts. Tfh2 cells were
      the only component that was not affected by glucocorticoid treatment, suggesting
      that Tfh2 cells are the cell type implicated in IgG4-related disease.

PMID- 25989155
TI  - Magnetic molecularly imprinted polymers synthesized by surface-initiated
      reversible addition-fragmentation chain transfer polymerization for the
      enrichment and determination of synthetic estrogens in aqueous solution.
AB  - Magnetic molecularly imprinted polymers have attracted significant interest
      because of their multifunctionality of selective recognition of target molecules
      and rapid magnetic response. In this contribution, magnetic molecularly imprinted
      polymers were synthesized via surface-initiated reversible addition addition
      fragmentation chain transfer polymerization using diethylstilbestrol as the
      template for the enrichment of synthetic estrogens. The uniform imprinted surface
      layer and the magnetic property of the magnetic molecularly imprinted polymers
      favored a fast binding kinetics and rapid analysis of target molecules. The
      static and selective binding experiments demonstrated a desirable adsorption
      capacity and good selectivity of the magnetic molecularly imprinted polymers in
      comparison to magnetic non-molecularly imprinted polymers. Accordingly, a
      corresponding analytical method was developed in which magnetic molecularly
      imprinted polymers were employed as magnetic solid-phase extraction materials for
      the concentration and determination of four synthetic estrogens
      (diethylstilbestrol, hexestrol, dienestrol, and bisphenol A) in fish pond water.
      The recoveries of these synthetic estrogens in spiked fish pond water samples
      ranged from 61.2 to 99.1% with a relative standard deviation of lower than 6.3%.
      This study provides a versatile approach to prepare well-defined magnetic
      molecularly imprinted polymers sorbents for the analysis of synthetic estrogens
      in water solution. 

PMID- 25989154
TI  - Transcutaneous electrical acupoint stimulation for the treatment of withdrawal
      syndrome in heroin addicts.
AB  - OBJECTIVE: To assess the therapeutic effect of transcutaneous electric acupoint
      stimulation (TEAS) for the treatment of withdrawal syndrome in heroin addicts.
      METHODS: A total of 63 male heroin addicts with withdrawal score higher than 20
      were recruited in the Detoxification Center of Zhongshan city, Guangdong
      province, China. They were randomly distributed into two groups: TEAS group (n =
      31) received TEAS by using a Han's acupoint nerve stimulator (HANS) model 200A
      with two output channels, 2-3 sessions per day, 30 minutes per session for 10
      consecutive days. Electrical stimulation of alternating frequencies of 2- and 100
      Hz with 3 second each, and with intensity of 10-15 mA was applied on Hegu (LI-4)
      and Laogong (PC-8) points on one hand, and Neiguan (PC-6) and Waiguan (SJ-5)
      points on the other forearm via electroconductive skin pads of 4 cm * 4 cm in
      size. The control group (n = 32) was treated with similar procedure except that
      the leads of the output of the stimulator was disconnected. Assessments of the
      severity of the withdrawal syndrome were conducted one day before and on each day
      during the whole treatment period of 10 days. Buprenorphin of 1 mg per day
      sublingually was provided to all subjects in the first two days, and then to
      those with withdrawal score over 20 in the following days. RESULTS: The TEAS
      treatment dramatically alleviated the withdrawal syndrome during heroin
      detoxification. No significant difference was found in withdrawal scores between
      the two groups at the beginning of the observation. Withdrawal scores showed a
      more marked drop in TEAS group than the control starting from the second day, and
      maintained at a lower level for the whole course of treatment. The area under the
      curve of withdrawal score in TEAS group was only 40% of that in the control (P <
      0.001, two way repeated measures analysis of variance), and the requirement of
      buprenorphine was only 10% of that in the control. No adverse effects were
      observed in either group. CONCLUSION: TEAS of 2/100 Hz for 10 days in abrupt
      abstinence of the heroin addicts resulted in a marked reduction of the withdrawal
      syndrome as well as a reduced requirement for rescue opioids.

PMID- 25989157
TI  - General Method for the Synthesis of Hollow Mesoporous Carbon Spheres with Tunable
      Textural Properties.
AB  - A versatile synthetic procedure to prepare hollow mesoporous carbon spheres
      (HMCS) is presented here. This approach is based on the deposition of a
      homogeneous hybrid polymer/silica composite shell on the outer surface of silica
      spheres through the surfactant-assisted simultaneous polycondensation of silica
      and polymer precursors in a colloidal suspension. Such composite materials can be
      further processed to give hollow mesoporous carbon spheres. The flexibility of
      this method allows for independent control of the morphological (i.e., core
      diameter and shell thickness) and textural features of the carbon spheres. In
      particular, it is demonstrated that the size of the pores within the mesoporous
      shell can be precisely tailored over an extended range (2-20 nm) by simply
      adjusting the reaction conditions. In a similar fashion, also the specific carbon
      surface area as well as the total shell porosity can be tuned. Most importantly,
      the textural features can be adjusted without affecting the dimension or the
      morphology of the spheres. The possibility to directly modify the shell textural
      properties by varying the synthetic parameters in a scalable process represents a
      distinct asset over the multistep hard-templating (nanocasting) routes. As an
      exemplary application, Pt nanoparticles were encapsulated in the mesoporous shell
      of HMCS. The resulting Pt@HMCS catalyst showed an enhanced stability during the
      oxygen reduction reaction, one of the most important reactions in
      electrocatalysis. This new synthetic procedure could allow the expansion, perhaps
      even beyond the lab-scale, of advanced carbon nanostructured supports for
      applications in catalysis. 

PMID- 25989156
TI  - Redox-Induced Backbiting of Surface-Tethered Alkylsulfonate Amphiphiles:
      Reversible Switching of Surface Wettability and Adherence.
AB  - The synthesis and characterization of electrode-supported poly(ferrocenylsilane)
      (PFS) films bearing iodopropyl (PFS-I) and undecanesulfonate (PFS-SO3(-)) surface
      moieties are presented. The redox responsiveness of these PFS films allows for
      controlled and repeatable switching of the surface energy of the PFS-I and PFS
      SO3(-) layers under electrochemical control. Static water/surface contact angle
      measurements showed a change in contact angle values for PFS-I from 80 degrees 
      (reduced state) to 70 degrees  (oxidized state) over repeated cycles. However, an
      opposite change in wettability was observed for PFS-SO3(-), where the values
      observed varied from 59 degrees  (reduced state) to 77 degrees  (oxidized state).
      Nanoscale adherence was assessed with colloid probe AFM. The adhesive forces
      between these surfaces and a polystyrene (PS) colloid probe in water alternated
      between 130 nN (reduced state) and 30 nN (oxidized state) for PFS-I layers and
      between 75 nN (reduced) and 180 nN (oxidized) for the PFS-SO3(-) films. The
      reversed response of PFS-I films to oxidation compared to that of PFS-SO3(-), in
      both contact angles and adhesive forces, suggests a different underlying
      mechanism for switching. As PFS-I is tuned from the reduced to the oxidized
      state, positively charged ferrocenium (Fc(+)) centers that formed in the film
      increase its wettability and reduce its adherence to the hydrophobic colloid
      probe. For PFS-SO3(-) in the reduced state, the exposed alkanesulfonate moieties
      increase the hydrophilicity of the surface. When oxidized, the Fc(+) units
      attract the negatively charged sulfonate groups, which results in a bending of
      the sulfonate groups toward the PFS surface, exposing the undecyl spacer. This
      alteration of the surface chemistry reduces the surface energy and increases the
      adherence between the bent alkyl chains and the hydrophobic PS colloid in water.
      The attraction of the charged sulfonate group to Fc(+) is in competition with the
      counterions present in the electrolyte solution. Therefore, the backbiting of the
      chain can be achieved only in electrolytes where the affinity of Fc(+) for the
      ions is lower than for the sulfonate group, in agreement with the Hofmeister
      series. 

PMID- 25989159
TI  - A 53-Year-Old Man With Dysuria, Pyuria, and Genital Ulcers.

PMID- 25989158
TI  - Lectin-gated, mesoporous, photofunctionalized glyconanoparticles for glutathione
      responsive drug delivery.
AB  - A stimuli-responsive drug delivery system based on fluorescent, lectin-gated,
      mesoporous glyconanoparticles has been developed and evaluated in normal- and
      cancer lung epithelial cells. The gating process proved efficient, exhibiting
      good sealing properties in the absence of the glutathione redox trigger, avoiding
      premature release in normal cells. In the presence of higher levels of
      glutathione in cancer cells, the lectin gate was rapidly opened and the
      anticancer drug released. 

PMID- 25989160
TI  - 2D Monolayer MoS2-Carbon Interoverlapped Superstructure: Engineering Ideal Atomic
      Interface for Lithium Ion Storage.
AB  - A novel strategy for the controlled synthesis of 2D MoS2/C hybrid nanosheets
      consisting of the alternative layer-by-layer interoverlapped single-layer MoS2
      and mesoporous carbon (m-C) is demonstrated. Such special hybrid nanosheets with
      a maximized MoS2 /m-C interface contact show very good performance for lithium
      ion batteries in terms of high reversible capacity, excellent rate capability,
      and outstanding cycling stability.

PMID- 25989162
TI  - Perseveration causes automatization of checking behavior in obsessive-compulsive
      disorder.
AB  - Repeated checking leads to reductions in meta-memory (i.e., memory confidence,
      vividness and detail), and automatization of checking behavior (Dek, van den
      Hout, Giele, & Engelhard, 2014, 2015). Dek et al. (2014) suggested that this is
      caused by increased familiarity with the checked stimuli. They predicted that
      defamiliarization of checking by modifying the perceptual characteristics of
      stimuli would cause de-automatization and attenuate the negative meta-memory
      effects of re-checking. However, their results were inconclusive. The present
      study investigated whether repeated checking leads to automatization of checking
      behavior, and if defamiliarization indeed leads to de-automatization and
      attenuation of meta-memory effects in patients with OCD and healthy controls.
      Participants performed a checking task, in which they activated, deactivated and
      checked threat-irrelevant stimuli. During a pre- and post-test checking trial,
      check duration was recorded and a reaction time task was simultaneously
      administered as dual-task to assess automatization. After the pre- and post-test
      checking trial, meta-memory was rated. Results showed that relevant checking led
      to automatization of checking behavior on the RT measure, and negative meta
      memory effects for patients and controls. Defamiliarization led to de
      automatization measured with the RT task, but did not attenuate the negative meta
      memory effects of repeated checking. Clinical implications are discussed. 

PMID- 25989161
TI  - Genetic association study of circadian genes with seasonal pattern in bipolar
      disorders.
AB  - About one fourth of patients with bipolar disorders (BD) have depressive episodes
      with a seasonal pattern (SP) coupled to a more severe disease. However, the
      underlying genetic influence on a SP in BD remains to be identified. We studied
      269 BD Caucasian patients, with and without SP, recruited from university
      affiliated psychiatric departments in France and performed a genetic single
      marker analysis followed by a gene-based analysis on 349 single nucleotide
      polymorphisms (SNPs) spanning 21 circadian genes and 3 melatonin pathway genes. A
      SP in BD was nominally associated with 14 SNPs identified in 6 circadian genes:
      NPAS2, CRY2, ARNTL, ARNTL2, RORA and RORB. After correcting for multiple testing,
      using a false discovery rate approach, the associations remained significant for
      5 SNPs in NPAS2 (chromosome 2:100793045-100989719): rs6738097 (pc = 0.006),
      rs12622050 (pc = 0.006), rs2305159 (pc = 0.01), rs1542179 (pc = 0.01), and
      rs1562313 (pc = 0.02). The gene-based analysis of the 349 SNPs showed that
      rs6738097 (NPAS2) and rs1554338 (CRY2) were significantly associated with the SP
      phenotype (respective Empirical p-values of 0.0003 and 0.005). The associations
      remained significant for rs6738097 (NPAS2) after Bonferroni correction. The
      epistasis analysis between rs6738097 (NPAS2) and rs1554338 (CRY2) suggested an
      additive effect. Genetic variations in NPAS2 might be a biomarker for a seasonal
      pattern in BD. 

PMID- 25989163
TI  - Ebola from emergence to epidemic: the virus and the disease, global preparedness
      and perspectives.
AB  - Humans constantly encounter threats from many infectious, zoonotic, and
      devastating pathogens. Outbreaks of severe acute respiratory syndrome (SARS),
      bird flu, and swine flu posing pandemic threats have compelled health agencies to
      follow global preparedness for combating the emerging deadly pathogens. The
      outbreak in West Africa of highly contagious Ebola viral disease (EVD) that
      started in Guinea in December 2013, assumed global proportions to become the
      largest outbreak of EVD and the most prominent international health concern. With
      fatality rates of nearly 50%-90%, it has claimed, as of 11 April 2015, 10,619
      human lives out of a total of 25,626 cases reported worldwide. Ebola virus
      (EBOV), a member of Filoviridae family, is associated with severe, often lethal,
      hemorrhagic fever disease in humans and animals. The animal hosts, including non
      human primates and reservoir hosts (fruit bats), play a significant role in
      transmission and maintenance of EBOV in nature. Although no approved vaccine for
      the prevention of EVD currently exists, disease control can be greatly enhanced
      by timely laboratory confirmation through blood tests using enzyme-linked
      immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction
      (RT-PCR). Adherence to strict sanitary and hygienic measures, monitoring and
      surveillance of EBOV, as well as quarantine checks on international trade,
      transport, and visitors from affected countries are mandatory to prevent and
      control the spread of EVD. This review describes the salient properties of EBOV
      and the development of novel diagnostics, vaccines, and control strategies for
      this emerging disease of high public health concern and international emergency. 

PMID- 25989164
TI  - Filarial hydrocele: a neglected condition of a neglected tropical disease.
AB  - Filarial hydrocele is the most common chronic manifestation of lymphatic
      filariasis (LF) and poses a major public health burden to several filarial
      endemic countries. This review highlights the socio-economic impact of the
      disease, the role of the immune system in hydrocele development, current
      diagnostic approaches, and the control and management of filarial hydrocele. In
      the quest to facilitate the global effort to eliminate filarial hydrocele as a
      neglected tropical disease, a more comprehensive understanding of the mechanisms
      underlying the pathogenesis and development of the condition is important. In
      general, success has been achieved using annual treatment with ivermectin, but
      much remains to be done, particularly with late-stage infected individuals where
      surgery remains the only option. Studies have successfully demonstrated that
      inhibition of embryogenesis in adult female worms occurs after weeks of
      tetracycline treatment. Even more intriguing was the observation that the
      Wolbachia endosymbionts potently induce proinflammatory cytokines such as tumor
      necrosis factors (TNFs) and vascular endothelial growth factors (VEGFs), which
      are crucial for the development of filarial hydrocele. Furthermore, reports from
      human studies show that doxycycline treatment significantly ameliorates filarial
      hydrocele and markedly reverses early-stage filarial hydrocele. However, with the
      enormous challenges that face LF elimination such as global funding, logistics,
      civil wars, and drug resistance, a more relentless and collective approach from
      local governments as well as other stakeholders is needed to accelerate the fight
      against filarial hydrocele if the goal to eliminate it by 2020 is be to achieved.

PMID- 25989165
TI  - Prevalence and antimicrobial resistance of Salmonella serotypes isolated from
      retail chicken meat and giblets in Iran.
AB  - INTRODUCTION: Salmonella is one of the major foodborne pathogens responsible for
      outbreaks of foodborne illness in humans worldwide. METHODOLOGY: A total of 560
      samples of chicken meat and giblets were collected from retail markets for
      Salmonella identification, serotyping, and antimicrobial resistance testing.
      RESULTS: Salmonella was detected in 19.8% of samples. Among the five serotypes
      identified, S. Thompson was the predominant type (48.7%). High antimicrobial
      resistance rates were observed to nalidixic acid (92.8%), tetracycline (81%),
      trimethoprim (68.4%), sulfamethoxazole / trimethoprim (61.2%), streptomycin
      (56.7%), and kanamycin (36.9%). Although resistance to chloramphenicol (3.6%),
      amoxicillin-clavulanic acid (5.4%), and ampicillin (11.7%) was detected, none of
      the isolates were resistant to ceftazidime, ceftriaxone, cefotaxime,
      ciprofloxacin, colistin, gentamicin, nor imipenem. CONCLUSIONS: Restrictions on
      the irrational use of antibiotics in humans and animals are suggested for the
      reduction of resistant strains.

PMID- 25989166
TI  - Serological, cultural, and molecular evidence of Brucella infection in small
      ruminants in Pakistan.
AB  - INTRODUCTION: The objectives of the present study were to determine the
      seroprevalence and identify the causative agent of brucellosis in small ruminants
      in Pakistan. METHODOLOGY: A total of 278 serum and 212 milk samples were
      collected from sheep and goats that had close contact with seropositive bovine
      herds. Data related to age, sex, location, and breed were collected on the
      sampling day. Serum and milk samples were initially screened using two different
      Rose Bengal plate test (RBPT) antigens and a milk ring test (MRT). Seropositive
      samples were subjected to bacterial isolation and PCR analysis using Brucella
      genus-specific (bcsp31) and Brucella species-specific (IS711 for Brucella abortus
      and Brucella melitensis) quantitative real-time polymerase chain reactions (qRT
      PCR). RESULTS: Twenty-four (8.6%) serum samples were positive by RBPT. Twenty
      (9.4%) animals were positive for Brucella antibodies using MRT. No Brucella
      isolates were obtained from the examined blood and milk samples. Of the 24
      seropositive serum samples, 18 (75%) were positive in the Brucella genus-specific
      (bcsp31) and Brucella abortus-specific (IS711) qRT-PCR, respectively.
      CONCLUSIONS: Brucella abortus was identified as causative agent of ovine and
      caprine brucellosis in Pakistan. Results of this study can be used for the
      development of an effective control and eradication strategy for brucellosis in
      livestock, especially small ruminants.

PMID- 25989167
TI  - Colistin alone or combined with sulbactam or carbapenem against A. baumannii in
      ventilator-associated pneumonia.
AB  - INTRODUCTION: Colistin use has increased over the last ten years because of
      multidrug-resistant microorganisms. The aim of this study was to compare the
      clinical and microbiological efficacy of colistin alone or in combination with
      sulbactam or carbapenem in the treatment of ventilator-associated pneumonia (VAP)
      due to multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii.
      METHODOLOGY: Cases treated for VAP because of MDR and XDR A. baumannii between
      January 2011 and January 2013 were included in the study. The primary and
      secondary outcome for colistin alone, colistin with sulbactam, and colistin with
      carbapenems were evaluated. The primary outcomes were clinical efficacy and
      microbiological efficacy; the secondary outcomes were nephrotoxicity, length of
      hospitalization, and mortality. RESULTS: A total of 70 VAP patients were
      evaluated. A total of 17 patients (24.3%) were administered colistin alone, 20
      patients (28.6%) were administered colistin and sulbactam, and 33 patients
      (47.1%) were administered colistin and carbapenem. Clinical and microbiological
      response rates were higher in the carbapenem combination group (63.6% and 63.6%
      in both) than in the sulbactam combination group, which registered 55.0% and
      60.0%, respectively. However, this did not represent a significant difference
      statistically (p > 0.05). There was also no significant difference between
      colistin alone and the combination groups regarding clinical and microbiological
      efficacy and mortality. CONCLUSIONS: Neither the administration of colistin alone
      nor colistin combined with either sulbactam or carbapenem had any noticeable
      advantage in the treatment of VAP in terms of clinical response, microbiological
      response, nephrotoxicity, length of hospitalization, and mortality.

PMID- 25989169
TI  - Antibiotic resistance and virulence genes of extraintestinal pathogenic
      Escherichia coli from tropical estuary, South India.
AB  - INTRODUCTION: Escherichia coli strains can cause a variety of intestinal and
      extraintestinal diseases. Extraintestinal pathogenic E. coli (ExPEC) strains have
      the ability to cause severe extraintestinal infections. Multidrug resistance
      among ExPEC could complicate human infections. METHODOLOGY: Escherichia coli
      strains were isolated during the period of January 2010 to December 2012 from
      five different stations set at Cochin estuary. Susceptibility testing was
      determined by the disk-diffusion method using nine different antimicrobial
      agents. A total of 155 strains of Escherichia coli were screened for the presence
      of virulence factor genes including papAH, papC, sfa/focDE, iutA,and kpsMT II
      associated with ExPEC. RESULTS: Among the 155 E. coli isolates, 26 (16.77%),
      carried two or more virulence genes typical of ExPEC. Furthermore, 19.23% of the
      ExPEC isolates with multidrug resistance were identified to belong to
      phylogenetic groups B2 and D. Statistically significant association of iutA gene
      in ExPEC was found with papC (p < 0.001) and kpsMT II (p < 0.001) genes. ExPEC
      isolates were mainly resistant to ampicillin (23.07%), tetracycline (19.23%), co
      trimoxazole (15.38%), and cefotaxime (15.38%). The adhesion genes papAH and
      sfa/focDE were positively associated with resistance to gentamicin,
      chloramphenicol, and cefotaxime (p < 0.05). CONCLUSIONS: Co-occurrence of
      virulence factor genes with antibiotic resistance among ExPEC poses considerable
      threat to those who use this aquatic system for a living and for recreation.

PMID- 25989168
TI  - Effect of combination therapy between thyme oil and ciprofloxacin on ulcer
      forming Shigella flexneri.
AB  - INTRODUCTION: Shigella flexneri is a Gram-negative bacteria that has the ability
      to invade the epithelium of the colon and cause colon ulcers. METHODOLOGY: The
      ability of isolated Shigella flexneri from bloody diarrhea to cause colon ulcers
      was investigated by histopathological examination via oral administration of the
      bacteria to adult male albino Sprague-Dawley rats. The antibacterial activity of
      thyme oil, ciprofloxacin, and their combination were evaluated in vitro and in
      vivo. RESULTS: Oral administration of 12*108 CFU/mL of S. flexneri was able to
      cause colon ulcers. Thyme oil had the highest antibacterial activity among other
      investigated oils (minimum inhibitory concentration [MIC] 150uL/L). Ciprofloxacin
      had the highest antimicrobial activity against S. flexneri (MIC 0.4mg/L). The
      synergism between thyme oil and ciprofloxacin showed the maximum growth
      inhibition of S. flexneri. The synergistic activity of thyme oil and
      ciprofloxacin succeeded in healing the epithelial surface of the colon and
      decreased the inflammation of the lamina propria; it also decreased the bacterial
      load in the infected colon, while the commercial drug failed to heal the colon
      ulcer. Thyme oil, ciprofloxacin, and their combination showed different degrees
      of effects on the bacterial cell structure by transmission and scanning electron
      microscopes. CONCLUSIONS: The combination of thyme oil and ciprofloxacin gave
      synergistic activity, which proved to be more effective in inhibiting the growth
      of ulcer-forming S. flexneri, healing the colon ulcer, and decreasing
      infiltration of the lamina propria with inflammatory cells.

PMID- 25989170
TI  - Treatment of pediatric diarrhea: a simulated client study at private pharmacies
      of Ujjain, Madhya Pradesh, India.
AB  - INTRODUCTION: In low- and middle-income countries such as India, private
      pharmacies play an important role in medical treatments, offering advice for
      common illnesses such as diarrhea and respiratory tract infections. There is a
      need to explore the details of the dispensing practices at the private pharmacies
      in low- and middle-income countries. METHODOLOGY: The present study used
      simulated client methodology to assess the actual dispensing practices for
      patients with pediatric diarrhea at private pharmacies in an urban setting of an
      Indian province. RESULTS: This study identified 164 private pharmacies (84.10%)
      in the study setting that engaged in the practice of dispensing prescription
      drugs without prescriptions. Only about 40% asked clients if they had a
      prescription from a doctor. The average duration of consultations at the
      pharmacies was 1.3 minutes (range, 0.5-6 minutes). The dispensing of drugs was
      not in compliance with the recommended guidelines and regulations. The most
      commonly dispensed drugs were antibiotics (40.24%); of these, quinolones either
      alone or in combination with imidazoles were the most frequently dispensed. The
      other commonly dispensed drugs were antimotility drugs (31.10%) and Lactobacillus
      acidophilus (probiotics; 23.17%). The drugs were dispensed in inappropriate doses
      due to the absence of indications. CONCLUSIONS: Overuse and misuse of all these
      prescription drugs dispensed by pharmacies pose significant issues, such as
      resistance, dangerous side effects, and high costs. At the same time, the
      pharmacies did not dispense recommended drugs such as oral rehydration solution
      and zinc, which they are authorized to dispense without a prescription.

PMID- 25989171
TI  - Seroepidemiology of hepatitis B virus infection among Chinese schizophrenia
      patients.
AB  - INTRODUCTION: This study aimed to analyze the characteristics of HBsAg, HBsAb,
      coexistence of HBsAg and HBsAb, and the genotypic distribution of HBV in Chinese
      schizophrenia patients. METHODOLOGY: A total of 1,694 schizophrenia patients, 9
      85 years of age, were recruited for the present study. HBsAg, HBsAb, and HBV DNA
      were detected with commercial methods. ALT, AST, gamma-GT, TBIL, and IBIL were
      measured by an automatic biochemistry analyzer. All statistical analyses were
      performed with SPSS 13.0. RESULTS: The seroprevalence of HBsAg and HBsAb in 1,649
      schizophrenia patients was 11.0% and 54.6%, respectively. HBsAb seroprevalence
      significantly decreased with the duration of the disease (p = 0.0009). The lowest
      seroprevalence of HBsAg was determined in 9.4% of the patients who had had the
      illness for < 1 year, and then increased to 11.7%, 11.3% and 11.7% in the
      patients who had had the illness for 1-5 years, 6-10 years and > 10 years. HBsAg
      and HBsAb coexisted in 69 individuals, which comprised 4.2% of the total
      subjects, and in 38.1% of the HBsAg-positive patients. Additionally, HBV titers
      were quantified in 64 HBsAg-positive samples; the highest virus titer was
      6.14*108 copies/mL, while 12 patients had less than 500 copies/mL. Moreover,
      among 48 HBV strains isolated from 62 HBsAg-positive samples, 33 and 15 strains
      belonged to genotypes C and B, respectively. CONCLUSION: Genotypes B and C HBV
      were the dominant genotypes distributed in schizophrenia patients, and the HBsAb
      seroprevalence significantly decreased with illness duration. Effective
      prevention strategies for against HBV transmission are required.

PMID- 25989172
TI  - Determination of PFOR gene expression in strains of G. intestinalis with
      different inhibitory concentrations of metronidazole.
AB  - INTRODUCTION: Giardia intestinalis is the most important and common diarrhea
      causing parasitic protozoa worldwide with growing clinical relevance in public
      health. There are many documented cases of G. intestinalis resistance to
      metronidazole (MZ). Pyruvate: ferredoxin oxidoreductase (PFOR), the membrane
      localized enzyme, plays a key role in the development of resistance to drugs. The
      aim of the present study was to evaluate the difference in the levels of PFOR
      gene expression between MZ-resistant and MZ-susceptible strains of G.
      intestinatlis. METHODOLOGY: From 159 samples with G. intestinalis cysts, 48
      strains were successfully cultivated. Using specific pair primers, PFOR gene
      expressions were estimated in different groups of Giardia. The polymerase chain
      reaction (PCR) data were analyzed with Bayesian analysis of qRT-PCR data using
      MCMC.qpcr package, with relative expression software tool (REST) and quantitative
      PCR CopyCount web source. RESULTS: In the group of Giardia with minimum
      inhibitory concentration (MIC) of 6.3 uM, the level of PFOR gene expression was
      downregulated and compared with controls, differed by 1.5 to 2.8 times. At the
      same time, there was no significant difference in PFOR gene expression between
      the control (susceptible) group and the group with MIC of 3.2 uM. CONCLUSIONS:
      Though there is association between PFOR gene expression and metronidazole
      resistance of Giardia intestinalis, the level of PFOR gene expression cannot be a
      strong genetic marker to predict level of resistance to metronidazole based on
      MICs.

PMID- 25989173
TI  - An unidentified cluster of infection in the Peruvian Amazon region.
AB  - INTRODUCTION: Bartonella bacilliformis is the etiological agent of Carrion's
      disease, which is a neglected disease linked to people in low-socioeconomic
      populations in Andean valleys. An outbreak of B. bacilliformis was reported in a
      rural area of the Peruvian Amazon region. The aim of this study was to
      characterize this outbreak using molecular techniques. METHODOLOGY: Fifty-three
      blood samples from patients diagnosed with Carrion's disease were analyzed by
      molecular tools, using both a Bartonella-specific polymerase chain reaction (PCR)
      and an universal PCR, both based on 16S rRNA gene amplification. Additional water
      samples from the area were also analyzed. RESULTS: Unexpectedly, the samples were
      positive only when the universal PCR was used. Although environmental
      contamination cannot be ruled out, the results showed that Sphingomonas faeni was
      the possible causative agent of this outbreak, and that water was the most
      feasible infection source. CONCLUSIONS: Diagnosis by clinical criteria or
      microscopy may lead to misdiagnosis. There is a need to include molecular tools
      in the routine diagnosis of febrile syndromes, including Carrion's disease.

PMID- 25989174
TI  - Detection and genotyping of Leptospira spp. from the kidneys of a seemingly
      healthy pig slaughtered for human consumption.
AB  - INTRODUCTION: Leptospirosis is a zoonotic disease caused by pathogenic Leptospira
      spp.  Leptospirosis is maintained in an environment due to chronic kidney
      infection of a wide variety of domestic, peridomestic and wild reservoir mammals.
      In this study the role of pigs in maintenance of leptospires on the Caribbean
      island of St. Kitts was investigated. METHODOLOGY: The condemned kidneys of 60
      pigs slaughtered at a St. Kitts abattoir were screened by a quantitative-PCR for
      the presence of Leptospira spp. Positive samples were genotyped using a six-gene
      based multilocus sequence typing scheme. RESULTS: Leptospiral DNA was detected in
      the kidneys of one of the 60 pigs. Multilocus sequence typing identified the
      infecting species to be L. interrogans. CONCLUSIONS: Detection of this zoonotic
      pathogen in the kidneys of a seemingly healthy pig raises concerns regarding the
      subclinical carriers of the disease among the island's swine population.

PMID- 25989175
TI  - Haemorrhagic pneumonia caused by Stenotrophomonas maltophilia in two newborns.
AB  - Invasive procedures and antibiotic treatment increase the risk of nosocomial
      infections in neonatal intensive care units. Early identification and appropriate
      treatment is important. Herein we report two cases of massive hemorrhagic
      pneumonia caused by Stenotrophomonas maltophilia. The first case was diagnosed
      with congenital pneumonia; a chest tube was inserted because of pneumothorax on
      the third day of life. The second case had been referred with respiratory
      distress syndrome, and bilateral pneumothorax was present on admission. Upon
      follow up, the cases' clinical condition worsened; acute respiratory distress
      syndrome and massive pulmonary haemorrhage developed. After Stenotrophomonas
      maltophilia was isolated in blood cultures, the cases were treated successfully
      using a combination of trimethoprim/sulfamethoxazole and fluoroquinolone. 

PMID- 25989176
TI  - Brain tuberculosis-associated immune reconstitution inflammatory syndrome in an
      HIV-positive patient: a biopsy-proven case.
AB  - The case of an HIV-infected man from Eritrea previously diagnosed with
      tuberculosis, who presented neurological impairment and cerebral lesion after
      having voluntarily stopped anti-tubercular and antiretroviral therapies, is here
      reported. Treatments associated with steroids and mannitol were administered. The
      patient's condition improved, but neuroimaging showed a continuous worsening of
      the lesion, while a great immunological reconstitution was observed. Brain
      microsurgery was performed. A tuberculosis diagnosis was supported by
      pathological and microbiological examinations. Tuberculosis arising during immune
      reconstitution inflammatory syndrome is a complication of antiretroviral
      treatment and is considered to be an emerging disorder, especially in countries
      highly endemic for tuberculosis. 

PMID- 25989177
TI  - The production of information in the attention economy.
AB  - Online traces of human activity offer novel opportunities to study the dynamics
      of complex knowledge exchange networks, in particular how emergent patterns of
      collective attention determine what new information is generated and consumed.
      Can we measure the relationship between demand and supply for new information
      about a topic? We propose a normalization method to compare attention bursts
      statistics across topics with heterogeneous distribution of attention. Through
      analysis of a massive dataset on traffic to Wikipedia, we find that the
      production of new knowledge is associated to significant shifts of collective
      attention, which we take as proxy for its demand. This is consistent with a
      scenario in which allocation of attention toward a topic stimulates the demand
      for information about it, and in turn the supply of further novel information.
      However, attention spikes only for a limited time span, during which new content
      has higher chances of receiving traffic, compared to content created later or
      earlier on. Our attempt to quantify demand and supply of information, and our
      finding about their temporal ordering, may lead to the development of the
      fundamental laws of the attention economy, and to a better understanding of
      social exchange of knowledge information networks. 

PMID- 25989178
TI  - Unique Chiral Interpenetrating d-f Heterometallic MOFs as Luminescent Sensors.
AB  - One novel three-dimensional (3D) 3d-4f metal-organic framework (MOF),
      [TbZn(L)(CO3)2(H2O)]n (1) [HL = 4'-(4-carboxyphenyl)-2,2':6',2"-terpyridine], has
      been successfully synthesized and structurally characterized. Structural analysis
      shows that compound 1 features a unique chiral interpenetrating 3D framework for
      the first time. The resulting crystals of 1 are composed of enantiomers 1a (P41)
      and 1b (P43), as was clearly confirmed by the crystal structure and the
      corresponding circular dichroism (CD) analyses of eight randomly selected
      crystals. The investigations on CD spectra based on every single crystal clearly
      assigned the Cotton effect signals. The powder X-ray diffraction measurement of 1
      after being immersed in common solvents reveals that 1 possess excellent solvent
      stability. Furthermore, luminescent studies imply that 1 displays highly
      selective luminescent sensing of aldehydes, such as formol, acetaldehyde, and
      propanal. 

PMID- 25989179
TI  - A phase I trial of mushroom powder in patients with biochemically recurrent
      prostate cancer: Roles of cytokines and myeloid-derived suppressor cells for
      Agaricus bisporus-induced prostate-specific antigen responses.
AB  - BACKGROUND: Each year in the United States, nearly 50,000 prostate cancer
      patients exhibit a rise in prostate-specific antigen (PSA) levels, which can
      indicate disease recurrence. For patients with biochemically recurrent prostate
      cancer, we evaluated the effects of white button mushroom (WBM) powder on serum
      PSA levels and determined the tolerability and biological activity of WBM.
      METHODS: Patients with continuously rising PSA levels were enrolled in the study.
      Dose escalation was conducted in cohorts of 6; this ensured that no more than 1
      patient per cohort experienced dose-limiting toxicity (DLT). The primary
      objective was to evaluate treatment feasibility and associated toxicity. The
      secondary objectives were to determine WBM's effect on serum PSA/androgen levels;
      myeloid-derived suppressor cells (MDSCs); and cytokine levels. RESULTS: Thirty
      six patients were treated; no DLTs were encountered. The overall PSA response
      rate was 11%. Two patients receiving 8 and 14 g/d demonstrated complete response
      (CR): their PSA declined to undetectable levels that continued for 49 and 30
      months. Two patients who received 8 and 12 g/d experienced partial response (PR).
      After 3 months of therapy, 13 (36%) patients experienced some PSA decrease below
      baseline. Patients with CR and PR demonstrated higher levels of baseline
      interleukin-15 than nonresponders; for this group, we observed therapy-associated
      declines in MDSCs. CONCLUSIONS: Therapy with WBM appears to both impact PSA
      levels and modulate the biology of biochemically recurrent prostate cancer by
      decreasing immunosuppressive factors.

PMID- 25989180
TI  - LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and
      pharmacogenetic study.
AB  - Latrophilin 3 (LPHN3) is a brain-specific member of the G-protein coupled
      receptor family associated to both attention-deficit/hyperactivity disorder
      (ADHD) genetic susceptibility and methylphenidate (MPH) pharmacogenetics.
      Interactions of LPHN3 variants with variants harbored in the 11q chromosome
      improve the prediction of ADHD development and medication response. The aim of
      this study was to evaluate the role of LPHN3 variants in childhood ADHD
      susceptibility and treatment response in a naturalistic clinical cohort. The
      association between LPHN3 and ADHD was evaluated in 523 children and adolescents
      with ADHD and 132 controls. In the pharmacogenetic study, 172 children with ADHD
      were investigated. The primary outcome measure was the parent-rated Swanson,
      Nolan and Pelham Scale - version IV applied at baseline, first and third months
      of treatment with MPH. The results reported herein suggest the CGC haplotype
      derived from single nucleotide polymorphisms (SNPs) rs6813183, rs1355368 and
      rs734644 as an ADHD risk haplotype (P = 0.02, OR = 1.46). Although non
      significant after multiple testing correction, its interaction with the 11q
      chromosome SNP rs965560 slightly increases risk (P = 0.03, OR = 1.55). Homozygous
      individuals for the CGC haplotype showed faster response to MPH treatment as a
      significant interaction effect between CGC haplotype and treatment over time was
      observed (P < 0.001). Homozygous individuals for the GT haplotype derived from
      SNPs rs6551665 and rs1947275 showed a nominally significant interaction with
      treatment over time (P = 0.04). Our findings replicate previous findings
      reporting that LPHN3 confers ADHD susceptibility, and moderates MPH treatment
      response in children and adolescents with ADHD. 

PMID- 25989181
TI  - Skyrmion-Based Dynamic Magnonic Crystal.
AB  - A linear array of periodically spaced and individually controllable skyrmions is
      introduced as a magnonic crystal. It is numerically demonstrated that skyrmion
      nucleation and annihilation can be accurately controlled by a nanosecond spin
      polarized current pulse through a nanocontact. Arranged in a periodic array, such
      nanocontacts allow the creation of a skyrmion lattice that causes a periodic
      modulation of the waveguide's magnetization, which can be dynamically controlled
      by changing either the strength of an applied external magnetic field or the
      density of the injected spin current through the nanocontacts. The skyrmion
      diameter is highly dependent on both the applied field and the injected current.
      This implies tunability of the lowest band gap as the skyrmion diameter directly
      affects the strength of the pinning potential. The calculated magnonic spectra
      thus exhibit tunable allowed frequency bands and forbidden frequency bandgaps
      analogous to that of conventional magnonic crystals where, in contrast, the
      periodicity is structurally induced and static. In the dynamic magnetic crystal
      studied here, it is possible to dynamically turn on and off the artificial
      periodic structure, which allows switching between full rejection and full
      transmission of spin waves in the waveguide. These findings should stimulate
      further research activities on multiple functionalities offered by magnonic
      crystals based on periodic skyrmion lattices. 

PMID- 25989182
TI  - Hybrid Materials Based on Magnetic Layered Double Hydroxides: A Molecular
      Perspective.
AB  - Design of functional hybrids lies at the very core of synthetic chemistry as it
      has enabled the development of an unlimited number of solids displaying
      unprecedented or even improved properties built upon the association at the
      molecular level of quite disparate components by chemical design. Multifunctional
      hybrids are a particularly appealing case among hybrid organic/inorganic
      materials. Here, chemical knowledge is used to deploy molecular components
      bearing different functionalities within a single solid so that these properties
      can coexist or event interact leading to unprecedented phenomena. From a
      molecular perspective, this can be done either by controlled assembly of
      organic/inorganic molecular tectons into an extended architecture of hybrid
      nature or by intercalation of organic moieties within the empty channels or
      interlamellar space offered by inorganic solids with three-dimensional (MOFs,
      zeolites, and mesoporous hosts) or layered structures (phosphates, silicates,
      metal dichalcogenides, or anionic clays). This Account specifically illustrates
      the use of layered double hydroxides (LDHs) in the preparation of magnetic
      hybrids, in line with the development of soft inorganic chemistry processes (also
      called "Chimie Douce"), which has significantly contributed to boost the
      preparation hybrid materials based on solid-state hosts and subsequent
      development of applications. Several features sustain the importance of LDHs in
      this context. Their magnetism can be manipulated at a molecular level by adequate
      choice of constituting metals and interlayer separation for tuning the nature and
      extent of magnetic interactions across and between planes. They display
      unparalleled versatility in accommodating a broad range of anionic species in
      their interlamellar space that encompasses not only simple anions but chemical
      systems of increasing dimensionality and functionalities. Their swelling
      characteristics allow for their exfoliation in organic solvents with high
      dielectric strength, to produce two-dimensional nanosheets with atomic thickness
      that can be used as macromolecular building blocks in the assembly of
      nanocomposites. We describe how these advantageous properties turn LDHs into
      excellent vehicles for the preparation of multifunctional materials with
      increasing levels of complexity. For clarity, the reader will first find a
      succinct description of the most relevant aspects controlling the magnetism of
      LDHs followed by their use in the preparation of magnetic hybrids from a
      molecular perspective. This includes the intercalation anionic species of
      increasing nuclearity like paramagnetic mononuclear complexes, stimulus
      responsive molecular guests, one- and two-dimensional coordination polymers, or
      even preassembled 2D networks. This approach allows us to evolve from "dual
      function" materials with coexistence, for example, of magnetism and
      superconductivity, to smart materials in which the magnetic or structural
      properties of the LDH layers can be tuned by applying an external stimulus like
      light or temperature. We will conclude with a brief look into the promising
      features offered by magnetic nanocomposites based on LDHs and our views on the
      most promising directions to be pursued in this context. 

PMID- 25989183
TI  - New analytical solution to calculate linear absorption coefficients of beta
      radiations.
AB  - The paper deals with an alternative model of beta radiation transmissions through
      attenuation layers and brings another analytical description of this phenomenon.
      The model is validated with a reliable data set and brings a possibility to
      calculate characteristic material parameters with low uncertainties. Using no
      correction factors, these calculations can be considered fundamental and
      inspiring for further research in the field. 

PMID- 25989184
TI  - Determination of faecal inflammatory marker concentration as a noninvasive method
      of evaluation of pathological activity in children with inflammatory bowel
      diseases.
AB  - PURPOSE: The optimization of procedure evaluating the severity of inflammatory
      bowel diseases (IBD) using non-invasive methods. PATIENTS/METHODS: One hundred
      and nine children with IBD hospitalized in gastroenterology ward between 2009 and
      2011 participated in the study. Activity of the disease was evaluated in each
      patient. Concentration of three inflammatory markers: dimeric form of tumor
      pyruvate kinase (M2-PK), calprotectin and lactoferrin was evaluated using
      immunoenzymatic tests. RESULTS: Existence of a significant correlation between
      the faecal level of all tested markers and the stage of clinical activity of the
      disease was demonstrated in children with IBD, both in Crohn's disease (M2-PK
      p<0.01; calprotectin p=0.005; lactoferrin p<0.01) and in ulcerative colitis group
      (M2-PK p<0.01; calprotectin p=0.004; lactoferrin p<0.01). A significant
      difference in the level of markers was found between children with unclassified
      colitis and the group of patients with ulcerative colitis and Crohn's disease,
      but there was no difference between Crohn's disease and ulcerative colitis. The
      increase in the level of one marker correlated with increasing level of other
      markers (p<0.01). Faecal markers seem to correlate well with majority of
      indicators of inflammatory condition in blood. CONCLUSIONS: Measuring M2-PK,
      lactoferrin and calprotectin levels in faeces seem to be a useful indicator of
      the level of disease activity in children with IBD.

PMID- 25989185
TI  - Green Light to Plant Responses to Pathogens: The Role of Chloroplast Light
      Dependent Signaling in Biotic Stress.
AB  - Light has a key impact on the outcome of biotic stress responses in plants by
      providing most of the energy and many signals for the deployment of defensive
      barriers. Within this context, chloroplasts are not only the major source of
      energy in the light; they also host biosynthetic pathways for the production of
      stress hormones and secondary metabolites, as well as reactive oxygen species and
      other signals which modulate nuclear gene expression and plant resistance to
      pathogens. Environmental, and in particular, light-dependent regulation of immune
      responses may allow plants to anticipate and react more effectively to pathogen
      threats. As more information is gathered, increasingly complex models are
      developed to explain how light and reactive oxygen species signaling could
      interact with endogenous defense pathways to elicit efficient protective
      responses against invading microorganisms. The emerging picture places
      chloroplasts in a key position of an intricate regulatory network which involves
      several other cellular compartments. This article reviews current knowledge on
      the extent and the main features of chloroplast contribution to plant defensive
      strategies against biotic stress. 

PMID- 25989186
TI  - Enhanced photocatalytic hydrogen evolution efficiency using hollow microspheres
      of (CuIn)(x)Zn(2(1-x))S2 solid solutions.
AB  - Hollow spheres of multicomponent (CuIn)(x)Zn(2(1-x))S2 solid solutions have been
      rapidly synthesized by a salt-assisted aerosol decomposition method.
      (CuIn)(0.2)Zn(1.6)S2 hollow spheres with a band gap of 2.53 eV exhibited an
      excellent and stable photocatalytic activity of 360 MUmol h(-1) (50 mg
      photocatalysts) for hydrogen evolution from aqueous solutions containing
      sacrificial reagents (SO3(2-) and S(2-)) under visible light (lambda>= 420 nm)
      due to the well-crystallized microspheres and mesoporous structures. H2 evolution
      rate of the (CuIn)(0.2)Zn(1.6)S2 hollow spheres reached as high as 57 MUmol h(-1)
      (50 mg photocatalysts) even without Ru loading.

PMID- 25989187
TI  - Use of Ex Vivo Normothermic Perfusion for Quality Assessment of Discarded Human
      Donor Pancreases.
AB  - A significant number of pancreases procured for transplantation are deemed
      unsuitable due to concerns about graft quality and the associated risk of
      complications. However, this decision is subjective and some declined grafts may
      be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to
      transplantation may allow a more objective assessment of graft quality and reduce
      discard rates. We report ex vivo normothermic perfusion of human pancreases
      procured but declined for transplantation, with ABO-compatible warm oxygenated
      packed red blood cells for 1-2 h. Five declined human pancreases were assessed
      using this technique after a median cold ischemia time of 13 h 19 min. One
      pancreas, with cold ischemia over 30 h, did not appear viable and was excluded.
      In the remaining pancreases, blood flow and pH were maintained throughout
      perfusion. Insulin secretion was observed in all four pancreases, but was lowest
      in an older donation after cardiac death pancreas. Amylase levels were highest in
      a gland with significant fat infiltration. This is the first study to assess the
      perfusion, injury, as measured by amylase, and exocrine function of human
      pancreases using EVNP and demonstrates the feasibility of the approach, although
      further refinements are required. 

PMID- 25989188
TI  - Review of general practitioners perception of a rural New South Wales outreach
      rehabilitation service.

PMID- 25989190
TI  - Quality and fatty acid profile of the milk of indigenous goats subjected to
      different local diets in Tunisian arid lands.
AB  - The study tested the hypothesis that certain pastoral forages and olive by
      products, available in arid areas, may positively influence fatty acid
      composition and physicochemical properties of goat's milk. Thirty indigenous
      goats (body weight = 25.2 kg; age = 4.1 years) were allocated to three groups.
      During 60 days, the goats received ad libitum either dried olive leaves + Stipa
      tenacissima (group OL), khortane grass hay (group Ko) or oat hay (control diet,
      group OH). Milk samples were collected and analysed for total solids, fat,
      protein, lactose and ash content and fatty acid profile. Average milk yield did
      not statistically differ among groups. Milk total solids from OL group were
      higher in comparison with Ko and C groups (15.3, 14.7 and 14.5%, respectively; p
      < 0.05). Fat content was also higher for the OL group as compared to the other
      groups (5.44 vs. 5.01 and 4.66%, respectively, for Ko and OH). No significant
      differences were observed for the milk content of lactose, protein and ash. The
      percentage of saturated fatty acids of total milk fat was higher in OL and Ko
      groups compared to the C group (p < 0.001); the milk whereof was characterized by
      the highest percentage of monounsaturated (p < 0.01) and total unsaturated fatty
      acids. Milk fat of Ko and C groups showed significantly higher proportions of
      rumenic (CLA cis-9 trans-11) and vaccenic acids (C18:1 trans-11) compared to OL
      milk. The feeding system based on Stipa tenacissima and dried olive leaves
      resulted in the milk lowest proportion of trans-fatty acids and the highest
      proportion of polyunsaturated omega3-fatty acids (p < 0.05).

PMID- 25989189
TI  - Sequence Type 4821 Clonal Complex Serogroup B Neisseria meningitidis in China,
      1978-2013.
AB  - Serogroup B Neisseria meningitidis strains belonging to sequence type 4821 clonal
      complex (CC4821), a hyperinvasive lineage first identified for serogroup C in
      2003, have been increasingly isolated in China. We characterized the outer
      membrane protein genes of 48 serogroup B and 214 serogroup C strains belonging to
      CC4821 and analyzed the genomic sequences of 22 strains. Four serogroup B strains
      had porin A (i.e., PorA), PorB, and ferric enterobactin transport (i.e., FetA)
      genotypes identical to those for serogroup C. Phylogenetic analysis of the
      genomic sequences showed that the 22 CC4821 strains from patients and healthy
      carriers were unevenly clustered into 2 closely related groups; each group
      contained serogroup B and C strains. Serogroup B strains appeared variable at the
      capsule locus, and several recombination events had occurred at uncertain
      breakpoints. These findings suggest that CC4821 serogroup C N. meningitidis is
      the probable origin of highly pathogenic CC4821 serogroup B strains. 

PMID- 25989192
TI  - State restrictions on the interstate practice of dermatopathology are
      unconstitutional: the tissue is the issue.
AB  - The regulation of the interstate practice of dermatopathology,
      teledermatopathology and teledermatology is the subject of discussion in many
      recent articles. Laws and regulations in many states complicate such interstate
      practice, requiring the dermatopathologist to be licensed in the state where the
      biopsy is taken if the dermatopathologist practices in and is licensed in a
      different state. To date, this discussion has been from the viewpoint of the
      dermatopathologist or dermatologist. But, when seen from the patient's viewpoint,
      its apparent that most such state regulation may be void as an unconstitutional
      infringement of a patient's fundamental right of unrestricted interstate travel
      under the Constitution of the United States of America. 

PMID- 25989191
TI  - Ability of Interleukin-33- and Immune Complex-Triggered Activation of Human Mast
      Cells to Down-Regulate Monocyte-Mediated Immune Responses.
AB  - OBJECTIVE: Mast cells have been implicated in the pathogenesis of rheumatoid
      arthritis (RA). In particular, their activation by interleukin-33 (IL-33) has
      been linked to the development of arthritis in animal models. The aim of this
      study was to evaluate the functional responses of human mast cells to IL-33 in
      the context of RA. METHODS: Human mast cells were stimulated with IL-33 combined
      with plate-bound IgG or IgG anti-citrullinated protein antibodies (ACPAs), and
      their effects on monocyte activation were evaluated. Cellular interactions of
      mast cells in RA synovium were assessed by immunofluorescence analysis, and the
      expression of messenger RNA (mRNA) for mast cell-specific genes was evaluated in
      synovial biopsy tissue from patients with early RA who were naive to treatment
      with disease-modifying antirheumatic drugs. RESULTS: IL-33 induced the up
      regulation of Fcgamma receptor type IIa and enhanced the activation of mast cells
      by IgG, including IgG ACPAs, as indicated by the production of CXCL8/IL-8.
      Intriguingly, mast cell activation triggered with IL-33 and IgG led to the
      release of mediators such as histamine and IL-10, which inhibited monocyte
      activation. Synovial mast cells were found in contact with CD14+
      monocyte/macrophages. Finally, mRNA levels of mast cell-specific genes were
      inversely associated with disease severity, and IL-33 mRNA levels showed an
      inverse correlation with the levels of proinflammatory markers. CONCLUSION: When
      human mast cells are activated by IL-33, an immunomodulatory phenotype develops,
      with human mast cells gaining the ability to suppress monocyte activation via the
      release of IL-10 and histamine. These findings, together with the presence of
      synovial mast cell-monocyte interactions and the inverse association between the
      expression of mast cell genes at the synovial level and disease activity, suggest
      that these newly described mast cell-mediated inhibitory pathways might have a
      functional relevance in the pathogenesis of RA.

PMID- 25989193
TI  - Effect of chemomechanical caries removal on bonding of resin-modified glass
      ionomer cement adhesives to caries-affected dentine.
AB  - BACKGROUND: This study evaluated the effect of: (1) chemomechanical caries
      removal (CMCR); (2) dentine surface treatments and (3) dentine substrates on
      adhesion of resin-modified glass ionomer cement (RMGIC) adhesives. METHODS: One
      hundred and twenty permanent molars exhibiting moderate cavitation on the
      occlusal surface into dentine were used. Seventy-five carious molars were used
      for bond strength testing; the remaining 45 for micromorphological evaluation of
      the bonded interface. Caries was excavated with NaOCl-based CMCR (Carisolv),
      enzyme-based CMCR (Papacarie), or conventional rotary caries removal methods.
      Dentine surface treatment was performed using 37% phosphoric acid, 25-30% PAA or
      20% PAA + 3% AlCl3 . RESULTS: Three-way ANOVA revealed that all three factors
      'caries removal methods', 'dentine surface treatments' and 'dentine substrates'
      did not significantly affect bond strength (p > 0.05). Scanning electron
      microscopy micrographs showed that the acid-base resistant layer was thicker in
      caries-affected dentine compared to sound dentine. CONCLUSIONS: NaOCl- and enzyme
      based CMCR methods have no adverse effect on adhesion of RMGIC adhesives to sound
      and caries-affected dentine. Dentine surface treatment with 37% phosphoric acid
      for 5 s has no negative effect on bonding of RMGIC adhesives to dentine compared
      with using polyacrylic acid for 10 s. RMGIC adhesives bonded well to both sound
      and caries-affected dentine.

PMID- 25989194
TI  - Preceptors' Expectations of Nursing Students' Preparation before Placement in
      Psychiatry: Ability and Will to Reflect on and Exercise Knowledge.
AB  - Nursing students must be prepared to provide nursing care regardless of the
      patient's illness. This requires that nursing education, including clinical
      placements, strengthen knowledge and skills in mental health nursing. The aim of
      this qualitative study was to describe 15 preceptors' expectations of nursing
      students' preparedness before they entered the psychiatric field. Data was
      collected with focus group interviews and analysed using conventional content
      analysis. The findings show that preceptors are concerned about the nursing
      students' will and ability to reflect on and exercise knowledge for managing the
      student role and themselves; for adapting their perspective on humanity; for
      their understanding of illness and how they are interacting with persons with
      mental illness. The conclusion is that the preceptors expect the educators to
      give sufficient theoretical knowledge and assess the students' personal maturity
      prior to entering the psychiatric field. 

PMID- 25989195
TI  - Access to Six- and Seven-Membered 1,7-Fused Indolines via Rh(III)-Catalyzed Redox
      Neutral C7-Selective C-H Functionalization of Indolines with Alkynes and Alkenes.
AB  - We report herein a new strategy for the Rh(III)-catalyzed redox-neutral C7
      selective C-H activation/annulation of indolines to rapidly access various
      privileged 1,7-fused indolines by utilizing an oxidizing-directing group. For
      example, a Rh(III)-catalyzed redox-neutral C7-selective C-H functionalization of
      indolines with arylalkynes is described to directly access 7-membered 1,7-fused
      indolines. Moreover, an unprecedented intramolecular addition of an alkenyl
      Cp*Rh(III) species to a carbamoyl moiety occurred to give 1H-pyrroloquinolinones
      when employing alkyl alkynes. Additionally, an efficient Rh(III)-catalyzed redox
      neutral C7-selective C-H activation/alkenylation/aza-Michael addition of
      indolines is also developed to give 6-membered 1,7-fused indolines. The
      advantages of these processes are as follows: (1) mild and simple reaction
      conditions; (2) no need for an external oxidant; (3) broad scope of substrates;
      and (4) valuable six- or seven-membered 1,7-fused indolines as products. 

PMID- 25989196
TI  - Ivabradine (Corlanor) for heart failure.

PMID- 25989197
TI  - Fluticason furoate (Arnuity Ellipta) for asthma.

PMID- 25989198
TI  - Ceftazidime/Avibactam (Avycaz) -- a new intraveneous antibiotic.

PMID- 25989199
TI  - Histoplasmosis in Idaho and Montana, USA, 2012-2013.

PMID- 25989200
TI  - Size, surface charge, and shape determine therapeutic effects of nanoparticles on
      brain and retinal diseases.
AB  - Nanoparticles can be valuable therapeutic options to overcome physical barriers
      to reach central nervous system. Systemically administered nanoparticles can pass
      through blood-neural barriers; whereas, locally injected nanoparticles directly
      reach neuronal and perineuronal cells. In this review, we highlight the
      importance of size, surface charge, and shape of nanoparticles in determining
      therapeutic effects on brain and retinal diseases. These features affect overall
      processes of delivery of nanoparticles: in vivo stability in blood and other body
      fluids, clearance via mononuclear phagocyte system, attachment with target cells,
      and penetration into target cells. Furthermore, they are also determinants of
      nano-bio interfaces: they determine corona formation with proteins in body
      fluids. Taken together, we emphasize the importance of considerations on
      characteristics of nanoparticles more suitable for the treatment of brain and
      retinal diseases in the development of nanoparticle-based therapeutics. FROM THE
      CLINICAL EDITOR: The central nervous system (CNS) remains an area where drug
      access and delivery are difficult clinically due to the blood brain barrier. With
      advances in nanotechnology, many researchers have designed and produced
      nanoparticle-based systems in an attempt to solve this problem. In this concise
      review, the authors described the current status of drug delivery to the CNS,
      based on particle size and shape. This article should stimulate more research to
      be done on future drug design.

PMID- 25989202
TI  - Habitat complexity influences fine scale hydrological processes and the incidence
      of stormwater runoff in managed urban ecosystems.
AB  - Urban ecosystems have traditionally been considered to be pervious features of
      our cities. Their hydrological properties have largely been investigated at the
      landscape scale and in comparison with other urban land use types. However,
      hydrological properties can vary at smaller scales depending upon changes in
      soil, surface litter and vegetation components. Management practices can directly
      and indirectly affect each of these components and the overall habitat
      complexity, ultimately affecting hydrological processes. This study aims to
      investigate the influence that habitat components and habitat complexity have
      upon key hydrological processes and the implications for urban habitat
      management. Using a network of urban parks and remnant nature reserves in
      Melbourne, Australia, replicate plots representing three types of habitat
      complexity were established: low-complexity parks, high-complexity parks, and
      high-complexity remnants. Saturated soil hydraulic conductivity in low-complexity
      parks was an order of magnitude lower than that measured in the more complex
      habitat types, due to fewer soil macropores. Conversely, soil water holding
      capacity in low-complexity parks was significantly higher compared to the two
      more complex habitat types. Low-complexity parks would generate runoff during
      modest precipitation events, whereas high-complexity parks and remnants would be
      able to absorb the vast majority of rainfall events without generating runoff.
      Litter layers on the soil surface would absorb most of precipitation events in
      high-complexity parks and high-complexity remnants. To minimize the incidence of
      stormwater runoff from urban ecosystems, land managers could incrementally
      increase the complexity of habitat patches, by increasing canopy density and
      volume, preserving surface litter and maintaining soil macropore structure. 

PMID- 25989203
TI  - Continuous-flow technology-a tool for the safe manufacturing of active
      pharmaceutical ingredients.
AB  - In the past few years, continuous-flow reactors with channel dimensions in the
      micro- or millimeter region have found widespread application in organic
      synthesis. The characteristic properties of these reactors are their
      exceptionally fast heat and mass transfer. In microstructured devices of this
      type, virtually instantaneous mixing can be achieved for all but the fastest
      reactions. Similarly, the accumulation of heat, formation of hot spots, and
      dangers of thermal runaways can be prevented. As a result of the small reactor
      volumes, the overall safety of the process is significantly improved, even when
      harsh reaction conditions are used. Thus, microreactor technology offers a unique
      way to perform ultrafast, exothermic reactions, and allows the execution of
      reactions which proceed via highly unstable or even explosive intermediates. This
      Review discusses recent literature examples of continuous-flow organic synthesis
      where hazardous reactions or extreme process windows have been employed, with a
      focus on applications of relevance to the preparation of pharmaceuticals. 

PMID- 25989204
TI  - Home for now: A mixed-methods evaluation of a short-term housing support program
      for homeless families.
AB  - The use of short-term rental subsidy vouchers offers a new approach to addressing
      the housing needs of families facing homelessness. In Massachusetts, the Family
      Home pilot program placed homeless families in housing instead of shelter,
      providing two years of rental subsidy plus support services with the goal of
      enabling families to maintain market rate housing. This mixed-method case study
      complements staff and participant interview data with participant survey and
      administrative data to evaluate the implementation and short-term outcomes of
      Family Home in one region. Data point to improved family well-being in housing
      but also persistent barriers to achieving longer-term housing and economic
      stability. Of the families who had exited the program at the end of the study,
      one quarter were able to retain their housing at market rate, only 9% returned to
      shelter, and one in five moved in with families/friends. Lack of affordable
      housing in a high rental cost region and jobs that pay living wages were among
      the major reasons that families struggled to maintain housing. This research
      points to the need for integrating supportive services from the program's start,
      including targeted workforce development, to plan for the end of the short-term
      rental subsidy. 

PMID- 25989205
TI  - A comment on the Brazilian contribution to the diagnosis and treatment of
      headache disorders.

PMID- 25989206
TI  - Treatment of headache following intra-arterial coiling for cerebral aneurysm with
      indomethacin.

PMID- 25989207
TI  - Trigger point injection reduces the pain of idiopathic intracranial hypotension.

PMID- 25989208
TI  - Cluster headache.

PMID- 25989210
TI  - Actinomycin D and nutlin-3a synergistically promote phosphorylation of p53 on
      serine 46 in cancer cell lines of different origin.
AB  - The p53 tumor suppressor protein is a transcription factor activated by
      phosphorylation of its N-terminus. MDM2, encoded by a p53-activated gene, acts as
      a negative-feedback regulator of p53 by promoting p53 degradation. Moreover, MDM2
      inhibits p53 by binding to and concealing its N-terminal transcription-activating
      domain. p53 can be activated by nutlin-3a, a molecule designed to bind MDM2 and
      prevent its interaction with p53. Actinomycin D promotes phosphorylation and
      accumulation of p53 via a mechanism that involves high expression of MDM2. We
      hypothesized that co-treatment of cells with actinomycin D and nutlin-3a would
      lead to synergistic activation of p53 by stimulating kinases and preventing
      accumulated MDM2 from binding to p53. Indeed, co-treatment of various cell lines
      with actinomycin D and nutlin-3a resulted in a synergistic increase of p53
      phosphorylation on serine 46. We focused on this residue because it is a marker
      of the highest level of p53 activation. Co-treatment was associated with
      conspicuous decrease in a marker of mTOR activity in NCI-H28 cells and very
      strong activation of p53 targets, including CDKN1A and PML, in A549 cells. Other
      p53 target genes (SESN1, SESN2, TIGAR, DRAM1) were also efficiently upregulated;
      however, a marker of apoptosis (active caspase-3) appeared only in some cancer
      cell lines (e.g., A375 and other cell lines derived from melanoma) indicating
      that phosphorylation of p53 on serine 46 is not straightforwardly associated with
      induction of apoptosis. Moreover, our data suggest that melanoma may be a
      suitable target for drug combination used in this study. 

PMID- 25989209
TI  - Direct current stimulation over the human sensorimotor cortex modulates the
      brain's hemodynamic response to tactile stimulation.
AB  - Tactile stimuli produce afferent signals that activate specific regions of the
      cerebral cortex. Noninvasive transcranial direct current stimulation (tDCS)
      effectively modulates cortical excitability. We therefore hypothesised that a
      single session of tDCS targeting the sensory cortices would alter the cortical
      response to tactile stimuli. This hypothesis was tested with a block-design
      functional magnetic resonance imaging protocol designed to quantify the blood
      oxygen level-dependent response to controlled sinusoidal pressure stimulation
      applied to the right foot sole, as compared with rest, in 16 healthy young
      adults. Following sham tDCS, right foot sole stimulation was associated with
      activation bilaterally within the precentral cortex, postcentral cortex, middle
      and superior frontal gyri, temporal lobe (subgyral) and cingulate gyrus.
      Activation was also observed in the left insula, middle temporal lobe, superior
      parietal lobule, supramarginal gyrus and thalamus, as well as the right inferior
      parietal lobule and claustrum (false discovery rate corrected, P < 0.05). To
      explore the regional effects of tDCS, brain regions related to somatosensory
      processing, and cortical areas underneath each tDCS electrode, were chosen as
      regions of interest. Real tDCS, as compared with sham tDCS, increased the percent
      signal change associated with foot stimulation relative to rest in the left
      posterior paracentral lobule. These results indicate that tDCS acutely modulated
      the cortical responsiveness to controlled foot pressure stimuli in healthy
      adults. Further study is warranted, in both healthy individuals and patients with
      sensory impairments, to link tDCS-induced modulation of the cortical response to
      tactile stimuli with changes in somatosensory perception. 

PMID- 25989211
TI  - Accelerated tooth movement with piezocision and its periodontal-transversal
      effects in patients with Class II malocclusion.
AB  - OBJECTIVE: To compare the extent of canine distalization and the transversal
      changes, postdistalization gingival indices, and mobility scores between patients
      who were undergoing orthodontic treatment involving upper premolar extraction
      with (experimental group) or without piezocision. MATERIALS AND METHODS: Twenty
      maxillary canines of 10 patients were evaluated with split mouth design. Pre- and
      postdistalization dental casts were prepared and scanned with an orthodontic
      scanner to compare the extent of distalization and transversal changes between
      the two groups. The pre- and postdistalization gingival indices and mobility
      scores were also calculated. RESULTS: Three-dimensional analysis of the models
      revealed significant differences in tooth movement (lesser anchorage loss and
      greater canine distalization) between the experimental and control groups.
      Furthermore, the distalization time was shortened in the experimental group.
      There were no differences in the transversal changes, pre- and postdistalization
      gingival indices, or mobility scores between groups. CONCLUSION: Piezocision
      assisted distalization accelerates tooth movement, decreases the anchorage loss
      for posterior teeth, and does not induce any maxillary transversal change.
      Moreover, piezocision does not have any adverse effects on periodontal health.

PMID- 25989212
TI  - Prevention of root resorption in hypofunctional teeth by occlusal function
      recovery.
AB  - OBJECTIVE: To clarify whether occlusal hypofunction is one of the key
      determinants for root resorption during tooth movement and root resorption is
      prevented by its recovery. MATERIALS AND METHODS: The rats were randomly divided
      into one control and two experimental groups: hypofunctional and recovery groups.
      In the hypofunctional group, an anterior metal cap and bite plate were attached
      to the maxillary and mandibular incisors to simulate occlusal hypofunction. In
      the recovery group, the appliances were removed 7 weeks after their use, and the
      rats were allowed to bite for 4 weeks after removal. At the age of 16 weeks, the
      upper first molars were moved and after 0, 7, 14, and 21 days, the maxillae were
      resected. The resorption area was quantified morphohistologically and tartrate
      resistant acid phosphatase (TRAP)-positive cells on the root surface were
      counted. We also examined the expressions of receptor activator of nuclear factor
      kappaB ligand (RANKL), macrophage-colony stimulating factor (M-CSF), and
      interleukin (IL)-8 immunohistochemically. RESULTS: The amount of root resorption
      and the number of TRAP-positive cells were significantly greater in the
      hypofunctional group than in the control and recovery groups. Moreover,
      immunoreactivity for RANKL, M-CSF, and IL-8 was detected in the periodontal
      ligament and on the root surface in the hypofunctional group. CONCLUSION:
      Occlusal hypofunction is one of the critical factors for root resorption;
      however, root resorption may be prevented by recovery of occlusal function.

PMID- 25989214
TI  - Remote platelet function testing--Significant progress towards widespread testing
      in clinical practice.

PMID- 25989213
TI  - Three-dimensional effects of the mini-implant-anchored Forsus Fatigue Resistant
      Device: A randomized controlled trial.
AB  - OBJECTIVE: To detect three-dimensionally the effects of using mini-implant
      anchorage with the Forsus Fatigue Resistant Device (FFRD). MATERIALS AND METHODS:
      The sample comprised 43 skeletal Class II females with deficient mandibles. They
      were randomly allocated into three groups: 16 patients (13.25 +/- 1.12 years)
      received FFRD alone (Forsus group), 15 subjects (13.07 +/- 1.41 years) received
      FFRD and mini-implants (FMI group), and 12 subjects (12.71 +/- 1.44 years) were
      in the untreated control group. Three-dimensional analyses of cone beam computed
      tomographic images were completed, and the data were statistically analyzed.
      RESULTS: Class I relationship and overjet correction were achieved in 88% of the
      cases. None of the two treatment groups showed significant mandibular skeletal
      effects. In the FMI group, significant headgear effect, decrease in maxillary
      width, and increase in the lower facial height were noted. In the FMI group,
      retroclination of maxillary incisors and distalization of maxillary molars were
      significantly higher. Proclination and intrusion of mandibular incisors were
      significantly greater in the Forsus group. CONCLUSIONS: FFRD resulted in Class II
      correction mainly through dentoalveolar effects and with minimal skeletal
      effects. Utilization of mini-implant anchorage effectively reduced the
      unfavorable proclination and intrusion of mandibular incisors but did not produce
      additional skeletal effects.

PMID- 25989215
TI  - [Upper Airway Stimulation in Obstructive Sleep Apnea].

PMID- 25989217
TI  - Synthetic and endogenous cannabinoids protect retinal neurons from AMPA
      excitotoxicity in vivo, via activation of CB1 receptors: Involvement of PI3K/Akt
      and MEK/ERK signaling pathways.
AB  - Cannabinoids have been suggested to protect retinal ganglion cells in different
      models of toxicity, but their effects on other retinal neurons are poorly known.
      We investigated the neuroprotective actions of the endocannabinoid N-arachidonoyl
      ethanolamine (Anandamide/AEA) and the synthetic cannabinoids R1-Methanandamide
      (MethAEA) and HU-210, in an in vivo retinal model of AMPA excitotoxicity, and the
      mechanisms involved in the neuroprotection. Sprague-Dawley rats were
      intravitreally injected with PBS or AMPA in the absence or presence of the
      cannabinoid agonists. Brain nitric oxide synthase (bNOS) and choline
      acetyltransferase (ChAT) immunoreactivity (IR), as well as TUNEL staining,
      assessed the AMPA-induced retinal amacrine cell loss and the dose-dependent
      neuroprotection afforded by cannabinoids. The CB1 receptor selective antagonist
      AM251 and the PI3K/Akt inhibitor wortmannin reversed the cannabinoid-induced
      neuroprotection, suggesting the involvement of CB1 receptors and the PI3K/Akt
      pathway in cannabinoids' actions. Experiments with the CB2 agonist JWH015 and
      [(3)H]CP55940 radioligand binding suggested that the CB2 receptor is not involved
      in the neuroprotection. AEA and HU-210 induced phosphorylation of Akt but only
      AEA induced phosphorylation of ERK1/2 kinases, as revealed by western blot
      analysis. To investigate the role of caspase-3 in the AMPA-induced cell death,
      the caspase-3 inhibitor Z-DEVD-FMK was co-injected with AMPA. Z-DEVD-FMK had no
      effect on AMPA excitotoxicity. Moreover, no difference was observed in the
      phosphorylation of SAPK/JNK kinases between PBS- and AMPA-treated retinas. These
      results suggest that endogenous and synthetic cannabinoids protect retinal
      amacrine neurons from AMPA excitotoxicity in vivo via a mechanism involving the
      CB1 receptors, and the PI3K/Akt and/or MEK/ERK1/2 signaling pathways. 

PMID- 25989216
TI  - Mangiferin supplementation improves serum lipid profiles in overweight patients
      with hyperlipidemia: a double-blind randomized controlled trial.
AB  - Our previous studies have shown that mangiferin decreased serum triglycerides and
      free fatty acids (FFAs) by increasing FFAs oxidation in both animal and cell
      experiments. This study sought to evaluate the effects of mangiferin on serum
      lipid profiles in overweight patients with hyperlipidemia. Overweight patients
      with hyperlipidemia (serum triglyceride >= 1.70 mmol/L, and total cholesterol >=
      5.2 mmol/L) were included in this double-blind randomized controlled trial.
      Participants were randomly allocated to groups, either receiving mangiferin (150
      mg/day) or identical placebo for 12 weeks. The lipid profile and serum levels of
      mangiferin, glucose, L-carnitine, beta-hydroxybutyrate, and acetoacetate were
      determined at baseline and 12 weeks. A total of 97 participants completed the
      trial. Compared with the placebo control, mangiferin supplementation
      significantly decreased the serum levels of triglycerides and FFAs, and insulin
      resistance index. Mangiferin supplementation also significantly increased the
      serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine,
      beta-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase
      activity. However, there were no differences in the serum levels of total
      cholesterol, low-density lipoprotein cholesterol, serum glucose, and insulin
      between groups. Mangiferin supplementation could improve serum lipid profiles by
      reducing serum triglycerides and FFAs in overweight patients with hyperlipidemia,
      partly due to the promotion of FFAs oxidation. 

PMID- 25989218
TI  - A resveratrol analog termed 3,3',4,4',5,5'-hexahydroxy-trans-stilbene is a potent
      HIV-1 inhibitor.
AB  - HIV resistance to current anti-HIV drugs and drug toxicity have created a need
      for new anti-HIV agents. We have examined and characterized a synthetic
      resveratrol analog, termed 3,3',4,4',5,5'-hexahydroxy-trans-stilbene (M8), for
      potential anti-HIV activity. Here, we demonstrate that M8 possesses potent anti
      HIV activity against several HIV variants with EC50 values in the low MUM range.
      M8 was shown to act at a very early step of HIV entry prior to fusion to host
      cells. These results demonstrate that this novel resveratrol derivative possesses
      potent anti-HIV-1 activity and may have a mechanism of action that is different
      from current anti-HIV-1 drugs including entry inhibitors. Further structure
      guided design might lead to the development of newer improved resveratrol
      derivatives that could have value either in therapy or as microbicides to prevent
      the sexual transmission of HIV-1.

PMID- 25989219
TI  - Hemoglobin H identification by high-performance liquid chromatography in
      confirmed hemoglobin H disease.
AB  - INTRODUCTION: Among hemoglobin (Hb) H disease cases diagnosed by DNA testing in
      our hemoglobinopathy laboratory, we have noted instances of unreported Hb H from
      high-performance liquid chromatography (HPLC) results of referring laboratories.
      METHODS: To characterize these issues, we identified all cases of genotypic Hb H
      disease diagnosed in our laboratory. HPLC chromatograms were reviewed to
      determine the presence and retention time of the Hb H peak. RESULTS: Hemoglobin H
      was not reported in 24.2% of patients (23 of 95) with genotypic Hb H disease. The
      characteristic prerun peak of Hb H was present on review of all eight Variant or
      Variant II beta-thalassemia short-program chromatograms. Elevated Hb F (>=3%) was
      reported in 14 cases. The Hb H peak was found in the Hb F window in 11 dual
      program cases. The incorrect identification of Hb H as elevated Hb F resulted in
      two testing referrals for 'deltabeta-thalassemia'. CONCLUSIONS: Hemoglobin H may
      go unreported due to failure to examine for or recognize its peak on Variant or
      Variant II beta-thalassemia short-program chromatograms. Elution of Hb H in the
      Hb F window resulted in misidentification of Hb H for Hb F and may indicate a
      Variant II HbA2 /HbA1C program software error. Our findings highlight the need
      for careful chromatogram inspection and clinical correlation in the diagnosis of
      Hb H disease.

PMID- 25989220
TI  - Differences in CART expression and cell cycle behavior discriminate sympathetic
      neuroblast from chromaffin cell lineages in mouse sympathoadrenal cells.
AB  - Adrenal medullary chromaffin cells and peripheral sympathetic neurons originate
      from a common sympathoadrenal (SA) progenitor cell. The timing and phenotypic
      changes that mark this lineage diversification are not fully understood. The
      present study investigated the expression patterns of phenotypic markers, and
      cell cycle dynamics, in the adrenal medulla and the neighboring suprarenal
      ganglion of embryonic mice. The noradrenergic marker, tyrosine hydroxylase (TH),
      was detected in both presumptive adrenal medulla and sympathetic ganglion cells,
      but with significantly stronger immunostaining in the former. There was intense
      cocaine and amphetamine-regulated transcript (CART) peptide immunostaining in
      most neuroblasts, whereas very few adrenal chromaffin cells showed detectable
      CART immunostaining. This phenotypic segregation appeared as early as E12.5,
      before anatomical segregation of the two cell types. Cell cycle dynamics were
      also examined. Initially, 88% of Sox10 positive (+) neural crest progenitors were
      proliferating at E10.5. Many SA progenitor cells withdrew from the cell cycle at
      E11.5 as they started to express TH. Whereas 70% of neuroblasts (TH+/CART+ cells)
      were back in the cell cycle at E12.5, only around 20% of chromaffin (CART
      negative) cells were in the cell cycle at E12.5 and subsequent days. Thus,
      chromaffin cell and neuroblast lineages showed differences in proliferative
      behavior from their earliest appearance. We conclude that the intensity of TH
      immunostaining and the expression of CART permit early discrimination of
      chromaffin cells and sympathetic neuroblasts, and that developing chromaffin
      cells exhibit significantly lower proliferative activity relative to sympathetic
      neuroblasts.

PMID- 25989221
TI  - Plexin-B3 suppresses excitatory and promotes inhibitory synapse formation in rat
      hippocampal neurons.
AB  - Molecular mechanisms underlying synaptogenesis and synaptic plasticity have
      become one of the main topics in neurobiology. Increasing evidence suggests that
      axon guidance molecules including semaphorins and plexins participate in synapse
      formation and elimination. Although class B plexins are widely expressed in the
      brain, their role in the nervous system remains poorly characterized. We
      previously identified that B-plexins modulate microtubule dynamics and through
      this impact dendrite growth in rat hippocampal neurons. Here, we demonstrate that
      Plexin-B2 and Plexin-B3 are present in dendrites, but do not localize in
      synapses. We find that overexpression of all B-plexins leads to decreased volume
      of excitatory synapses, and at the same time Plexin-B1 and Plexin-B3 promote
      inhibitory synapse assembly. Plexin-B3 mutants revealed that these processes use
      different downstream pathways. While elimination of excitatory synapses is the
      result of Plexin-B3 binding to microtubule end binding proteins EB1 and EB3, the
      increase in inhibitory synapses is mediated by regulation of Ras and Rho GTPases.
      Overall, our findings demonstrate that Plexin-B3 contributes to regulating
      synapse formation. 

PMID- 25989223
TI  - Acute Diastolic Heart Dysfunction Caused by Ruptured Descending Thoracic Aortic
      Aneurysm with Posterior Mediastinal Hematoma.

PMID- 25989222
TI  - Assessing switchability for biosimilar products: modelling approaches applied to
      children's growth.
AB  - The present paper describes two statistical modelling approaches that have been
      developed to demonstrate switchability from the original recombinant human growth
      hormone (rhGH) formulation (Genotropin((r)) ) to a biosimilar product
      (Omnitrope((r)) ) in children suffering from growth hormone deficiency.
      Demonstrating switchability between rhGH products is challenging because the
      process of growth varies with the age of the child and across children. The first
      modelling approach aims at predicting individual height measured at several time
      points after switching to the biosimilar. The second modelling approach provides
      an estimate of the deviation from the overall growth rate after switching to the
      biosimilar, which can be regarded as an estimate of switchability. The results
      after applying these approaches to data from a randomized clinical trial are
      presented. The accuracy and precision of the predictions made using the first
      approach and the small deviation from switchability estimated with the second
      approach provide sufficient evidence to conclude that switching from
      Genotropin((r)) to Omnitrope((r)) has a very small effect on growth, which is
      neither statistically significant nor clinically relevant.

PMID- 25989225
TI  - Evaluation of the pharmacokinetics of oral amitriptyline and its active
      metabolite nortriptyline in fed and fasted Greyhound dogs.
AB  - This study reports the pharmacokinetics of oral amitriptyline and its active
      metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were
      enrolled in a randomized crossover design. A single oral dose of amitriptyline
      hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed
      dogs. Blood samples were collected at predetermined times from 0 to 24 h after
      administration, and plasma drug concentrations were measured by liquid
      chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses
      were performed. Two dogs in the fasted group vomited following amitriptyline
      administration and were excluded from analysis. The range of amitriptyline CMAX
      for the remaining fasted dogs (n = 3) was 22.8-64.5 ng/mL compared to 30.6-127
      ng/mL for the fed dogs (n = 5). The range of the amitriptyline AUCINF for the
      three fasted dogs was 167-720 h.ng/mL compared to 287-1146 h.ng/mL for fed dogs.
      The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs
      was 69-91% (n = 3). The exposure of the active metabolite nortriptyline was
      correlated to amitriptyline exposure (R(2)  = 0.84). Due to pharmacokinetic
      variability and the small number of dogs completing this study, further studies
      are needed assessing the impact of feeding on oral amitriptyline
      pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted
      dogs. 

PMID- 25989224
TI  - Allosteric modulation of sigma-1 receptors elicits anti-seizure activities.
AB  - BACKGROUND AND PURPOSE: Application of orthosteric sigma-1 receptor agonists as
      anti-seizure drugs has been hindered by questionable efficacy and potential
      adverse effects. Here, we have investigated the anti-seizure effects of the novel
      and potent allosteric modulator of sigma-1 receptors, SKF83959 and its derivative
      SOMCL-668 (3-methyl-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol).
      EXPERIMENTAL APPROACH: The anti-seizure effects of SKF83959 were investigated in
      three mouse models, maximal electroshock seizures, pentylenetetrazole-induced
      convulsions and kainic acid-induced 'status epilepticus'. Also, in rats, the
      cortical epileptiform activity induced by topical application of picrotoxin was
      recorded in electrocorticograms. In rat hippocampal brain slices, effects of the
      drugs on the high potassium-evoked epileptiform local field potentials were
      studied. Anti-seizure activities of SOMCL-668, a newly developed sigma-1 receptor
      selective allosteric modulator, were also investigated. KEY RESULTS: SKF83959
      (20, 40 mg.kg(-1) ) exhibited anti -seizure actitity in the three mouse models
      and reduced the cortical epileptiform activity without alteration of spontaneous
      motor activity and motor coordination. These effects were blocked by the sigma-1
      receptor antagonist BD1047, but not the dopamine D1 receptor antagonist SCH23390.
      SKF83959 alone did not directly inhibit the epileptiform firing of CA3 neurons
      induced by high potassium in hippocampal slices, but did potentiate inhibition by
      the orthosteric sigma-1 receptor agonist SKF10047. Lastly, a selective sigma-1
      receptor allosteric modulator SOMCL-668, which does not bind to dopamine
      receptors, exerted similar anti-seizure activities. CONCLUSIONS AND IMPLICATIONS:
      SKF83959 and SOMCL-668 displayed anti-seizure activities, indicating that
      allosteric modulation of sigma-1 receptors may provide a novel approach for
      discovering new anti-seizure drugs.

PMID- 25989226
TI  - Effects of Geographical Accessibility on the Use of Outpatient Care Services:
      Quasi-Experimental Evidence from Panel Count Data.
AB  - In 2010-2012, new outpatient service locations were established in Hungarian
      micro-regions, which had lacked such capacities before. We exploit this quasi
      experiment to estimate the effect of geographical accessibility on outpatient
      case numbers using both individual-level and semi-aggregate panel data. We find a
      24-27 per cent increase of case numbers as a result of the establishments. Our
      specialty-by-specialty estimates imply that a 1-min reduction of travel time to
      the nearest outpatient unit increases case numbers for example by 0.9 per cent in
      internal care and 3.1 per cent in rheumatology. The size of the new outpatient
      capacities has a separate effect, raising the possibility of the presence of
      supplier-induced demand. By combining a fixed-effects logit and a fixed-effects
      truncated Poisson estimator, we decompose the effects into increases in the
      probability of ever visiting a doctor on the one hand and an increase of the
      frequency of visits on the other hand. We find that new visits were dominant in
      the vast majority of specialties, whereas both margins were important for example
      in rheumatology. Finally, we demonstrate the usefulness of the fixed-effects
      truncated Poisson estimator in modelling count data by examining its robustness
      by simulations.

PMID- 25989229
TI  - Unbound ritonavir concentrations in rat and human hepatocytes.
AB  - Knowledge regarding intracellular drug exposure is crucial to gain mechanistic
      understanding of hepatic disposition. This study aims to develop an approach to
      determine unbound intracellular concentrations (Cu,cell ) of ritonavir. Ritonavir
      was selected as a model drug as incubations with high ritonavir concentrations
      inhibited all saturable processes involved in ritonavir disposition including
      metabolism and transporter-mediated membrane passage. Following this incubation,
      hepatocytes were re-equilibrated in fresh protein-containing medium before
      determination of extracellular unbound ritonavir concentrations. In the absence
      of metabolism and transport, unbound intracellular and unbound extracellular
      concentrations were identical. In parallel, total intracellular ritonavir
      concentrations (Ccell ) were determined, enabling the calculation of
      intracellular free fractions (fu,cell ). Additionally, Ccell was determined after
      exposing hepatocytes to a therapeutically relevant concentration (0.5 MUM).
      Multiplication of this concentration with fu,cell resulted in Cu,cell . Finally,
      Kpu,u (intracellular unbound drug accumulation ratio) was calculated. Exposure of
      rat and human hepatocytes to 0.5 MUM ritonavir resulted in Cu,cell of 12 +/- 1
      and 8 +/- 1 nM. Corresponding Kpu,u values were 2.7 +/- 0.5 and 1.4 +/- 0.2. We
      present an in vitro method to determine Cu,cell of ritonavir in intact
      hepatocytes. Cu,cell obtained at clinically relevant extracellular concentrations
      are in accordance with concentrations known to inhibit cytochrome P450 and are
      achieved because of ritonavir accumulation in hepatocytes.

PMID- 25989228
TI  - New ambuic acid derivatives from the solid culture of Pestalotiopsis neglecta and
      their nitric oxide inhibitory activity.
AB  - Four new ambuic acid derivatives (1-4), and four known derivatives (5-8), were
      isolated from the solid culture of a plant pathogenic fungus Pestalotiopsis
      neglecta. Their structures were elucidated by extensive NMR experiments. The
      absolute configuration of the C-16 secondary alcohol in 1 was deduced via the CD
      data of the in situ formed [Rh2(OCOCF3)4] complex with the acetonide derivative
      of 1. The absolute configuration in 3 was assigned by comparison of the
      experimental and simulated electronic circular dichroism (ECD) spectrum. The NMR
      data of compound 5 was reported for the first time. In the nitric oxide (NO)
      inhibition assay, compounds 4, 6 and 7 showed inhibitory activity against the NO
      production in the lipopolysaccharide (LPS)-induced macrophage with IC50 values of
      88.66, 11.20, and 20.80 uM, respectively.

PMID- 25989227
TI  - Developmental trajectories in 22q11.2 deletion.
AB  - Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is
      the most common microdeletion syndrome affecting 1 in 2,000-4,000 live births and
      involving haploinsufficiency of ~50 genes resulting in a multisystem disorder.
      Phenotypic expression is highly variable and ranges from severe life-threatening
      conditions to only a few associated features. Most common medical problems
      include: congenital heart disease, in particular conotruncal anomalies; palatal
      abnormalities, most frequently velopharyngeal incompetence (VPI);
      immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary
      anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic
      facial features. The neurocognitive profile is also highly variable, both between
      individuals and during the course of development. From infancy onward, motor
      delays (often with hypotonia) and speech/language deficits are commonly observed.
      During the preschool and primary school ages, learning difficulties are very
      common. The majority of patients with 22q11.2DS have an intellectual level that
      falls in the borderline range (IQ 70-84), and about one-third have mild to
      moderate intellectual disability. More severe levels of intellectual disability
      are uncommon in children and adolescents but are more frequent in adults.
      Individuals with 22q11.2DS are at an increased risk for developing several
      psychiatric disorders including attention deficit with hyperactivity disorder
      (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic
      disorders and schizophrenia. In this review, we will focus on the developmental
      phenotypic transitions regarding cognitive development in 22q11.2DS from early
      preschool to adulthood, and on the changing behavioral/psychiatric phenotype
      across age, on a background of frequently complex medical conditions.

PMID- 25989230
TI  - Invasion dynamics of white-nose syndrome fungus, midwestern United States, 2012
      2014.
AB  - White-nose syndrome has devastated bat populations in eastern North America. In
      Midwestern United States, prevalence increased quickly in the first year of
      invasion (2012-13) but with low population declines. In the second year (2013
      14), environmental contamination led to earlier infection and high population
      declines. Interventions must be implemented before or soon after fungal invasion
      to prevent population collapse. 

PMID- 25989231
TI  - Vaccine immunotherapy in lung cancer: Clinical experience and future directions.
AB  - Lung cancer remains the most common cause of cancer-related deaths in the United
      States, with SEER data showing lung cancer accounting for 29% of all male-related
      cancer mortality and 26% of all female-related mortality. Patients with small
      cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) who have localized
      disease both have 5-year survival rates of 52.2%, whereas patients with
      metastatic disease have 5-year survival rates of only 3.7%. Traditional anti
      cancer therapies (surgery, radiotherapy, and chemotherapy) have limited
      effectiveness in curbing progression. However, advances in immunology and
      molecular biology in the past two decades have resulted in improved prognosis for
      those with SCLC and NSCLC, although novel therapies are still needed to make
      significant improvements in median overall and progression-free survival rates.
      Notable progress on the importance of tumor immunology has included work on
      immune surveillance, antigenic targets, and immune checkpoints. Immunotherapies,
      including vaccines, which can induce antitumor responses by harnessing the power
      of the immune system, may help to fill this void, and the cancer vaccine
      continues to be studied as adjunctive therapy. Here, we review recently reported
      results from clinical trials as well as the possible future roles of vaccine
      therapy in the treatment of SCLC and NSCLC patients. 

PMID- 25989232
TI  - Pathogenesis and treatment of the cardiorenal syndrome: Implications of L
      arginine-nitric oxide pathway impairment.
AB  - A highly complex interplay exists between the heart and kidney in the setting of
      both normal and abnormal physiology. In the context of heart failure, a
      pathophysiological condition termed the cardiorenal syndrome (CRS) exists whereby
      dysfunction in the heart or kidney can accelerate pathology in the other organ.
      The mechanisms that underpin CRS are complex, and include neuro-hormonal
      activation, oxidative stress and endothelial dysfunction. The endothelium plays a
      central role in the regulation of both cardiac and renal function, and as such
      impairments in endothelial function can lead to dysfunction of both these organs.
      In particular, reduced bioavailability of nitric oxide (NO) is a key
      pathophysiologic component of endothelial dysfunction. The synthesis of NO by the
      endothelium is critically dependent on the plasmalemmal transport of its
      substrate, L-arginine, via the cationic amino acid transporter-1 (CAT1). Impaired
      L-arginine-NO pathway activity has been demonstrated individually in heart and
      renal failure. Recent findings suggest abnormalities of the L-arginine-NO pathway
      also play a role in the pathogenesis of CRS and thus this pathway may represent a
      potential new target for the treatment of heart and renal failure. 

PMID- 25989234
TI  - The HIV-1 leader RNA is exquisitely sensitive to structural changes.
AB  - The untranslated leader of the HIV-1 RNA genome is highly structured and contains
      multiple replication signals. We probed in detail the sequence requirements of a
      small single-stranded domain using a combination of in silico, in vitro and in
      vivo virus experiments. Although 'structure-neutral' mutations can be designed by
      RNA prediction algorithms, experimental follow-up studies nearly always
      demonstrate local or regional RNA structure changes. Our results indicate that
      the wild-type HIV-1 RNA sequence has been selected from total sequence space as a
      unique solution to present critical replication signals in the context of a
      complex leader structure with small intervening single-stranded segments. 

PMID- 25989233
TI  - Artificial zinc finger DNA binding domains: versatile tools for genome
      engineering and modulation of gene expression.
AB  - Genome editing and alteration of gene expression by synthetic DNA binding
      activities gained a lot of momentum over the last decade. This is due to the
      development of new DNA binding molecules with enhanced binding specificity. The
      most commonly used DNA binding modules are zinc fingers (ZFs), TALE-domains, and
      the RNA component of the CRISPR/Cas9 system. These binding modules are fused or
      linked to either nucleases that cut the DNA and induce DNA repair processes, or
      to protein domains that activate or repress transcription of genes close to the
      targeted site in the genome. This review focuses on the structure, design, and
      applications of ZF DNA binding domains (ZFDBDs). ZFDBDs are relatively small and
      have been shown to penetrate the cell membrane without additional tags suggesting
      that they could be delivered to cells without a DNA or RNA intermediate. Advanced
      algorithms that are based on extensive knowledge of the mode of ZF/DNA
      interactions are used to design the amino acid composition of ZFDBDs so that they
      bind to unique sites in the genome. Off-target binding has been a concern for all
      synthetic DNA binding molecules. Thus, increasing the specificity and affinity of
      ZFDBDs will have a significant impact on their use in analytical or therapeutic
      settings.

PMID- 25989235
TI  - Role of CYP2D6 Polymorphisms in the Outcome of Postoperative Pain Treatment.
AB  - OBJECTIVE: To investigate the role of CYP2D6 phenotype in the outcome of
      postoperative (PO) pain (POP) treatment. DESIGN: Longitudinal cohort study. Open
      label trial with post hoc analysis. SETTING: General Hospital Surgery and
      Recovery Units. PATIENTS: Ninety unrelated Caucasians submitted to
      abdominal/thoracic surgery. INTERVENTIONS: Standard multimodal POP treatment
      including opioids (tramadol) and nonsteroidal anti-inflammatory drugs
      (ketoprofen) at different dosages and infusion rates according to the predicted
      mild, moderate, or severe POP. OUTCOME MEASURES: Pain (Numeric Rating Scale-NRS)
      and sedation (Ramsay Sedation Scale-RSS) up to 24 hours after surgery. By
      genotyping 16 CYP2D6 alleles, the four CYP2D6 phenotypes poor metabolizer (PM),
      intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid
      metabolizers (UM) were predicted. RESULTS: As compared with the CYP2D6-EM
      phenotype, in the early PO time (30 min) a higher RSS mean score in IM was
      observed (P = 0.035). A suggestion towards higher mean score in PM (P = 0.091)
      and a minor mean score in UM (P = 0.091) was also detected. No difference in the
      outcome of pain across the CYP2D6 phenotypes was observed. CONCLUSIONS: In
      respect to the normal CYP2D6 phenotype, our results suggested that slowly
      metabolizers (IMs and PMs) might have a major sedation, whereas more rapid
      metabolizers (UM) a minor sedation, in the early time after surgery. A minor role
      of CYP2D6 phenotype in PO analgesia may be suggested.

PMID- 25989236
TI  - Therapeutic Hypothermia Reduces Intracranial Pressure and Partial Brain Oxygen
      Tension in Patients with Severe Traumatic Brain Injury: Preliminary Data from the
      Eurotherm3235 Trial.
AB  - Traumatic brain injury (TBI) is a significant cause of disability and death and a
      huge economic burden throughout the world. Much of the morbidity associated with
      TBI is attributed to secondary brain injuries resulting in hypoxia and ischemia
      after the initial trauma. Intracranial hypertension and decreased partial brain
      oxygen tension (PbtO2) are targeted as potentially avoidable causes of morbidity.
      Therapeutic hypothermia (TH) may be an effective intervention to reduce
      intracranial pressure (ICP), but could also affect cerebral blood flow (CBF).
      This is a retrospective analysis of prospectively collected data from 17 patients
      admitted to the Western General Hospital, Edinburgh. Patients with an ICP >20
      mmHg refractory to initial therapy were randomized to standard care or standard
      care and TH (intervention group) titrated between 32 degrees C and 35 degrees C
      to reduce ICP. ICP and PbtO2 were measured using the Licox system and core
      temperature was recorded through rectal thermometer. Data were analyzed at the
      hour before cooling, the first hour at target temperature, 2 consecutive hours at
      target temperature, and after 6 hours of hypothermia. There was a mean decrease
      in ICP of 4.3+/-1.6 mmHg (p<0.04) from 15.7 to 11.4 mmHg, from precooling to the
      first epoch of hypothermia in the intervention group (n=9) that was not seen in
      the control group (n=8). A decrease in ICP was maintained throughout all time
      periods. There was a mean decrease in PbtO2 of 7.8+/-3.1 mmHg (p<0.05) from 30.2
      to 22.4 mmHg, from precooling to stable hypothermia, which was not seen in the
      control group. This research supports others in demonstrating a decrease in ICP
      with temperature, which could facilitate a reduction in the use of hyperosmolar
      agents or other stage II interventions. The decrease in PbtO2 is not below the
      suggested treatment threshold of 20 mmHg, but might indicate a decrease in CBF.

PMID- 25989237
TI  - Screening of GJB6 gene large deletions among Syrians with congenital hearing
      impairment.
AB  - BACKGROUND: Research into the genetics of congenital hearing impairment in the
      Syrian population, where cases are noticeably encountered, is still in its
      infancy. AIMS: Our goal was to estimate the frequencies of the del(GJB6-D13S1830)
      and del(GJB6-D13S1854) mutations in a group of Syrians with autosomal recessive
      nonsyndromic hearing loss (ARNSHL). METHODS: Forty-one unrelated Syrian probands,
      already screened for exon 2, GJB2 gene mutations, were reanalyzed for del(GJB6
      D13S1830) and del(GJB6-D13S1854) mutations by polymerase chain reaction. RESULTS:
      The del(GJB6-D13S1830) mutation was only found in homozygosity in 1 of 41
      probands (2.43%), while the del(GJB6-D13S1854) mutation was not detected in any
      of the enrolled patients. Coexistence of GJB2 and GJB6 mutations was not
      encountered in any case. CONCLUSIONS: Our study reports the first case in Syria
      with the del(GJB6-D13S1830) mutation. This mutation might be considered in the
      diagnosis and genetic counseling of inherited hearing impairment in the Syrian
      population.

PMID- 25989238
TI  - Differential Development of Systemic Lupus Erythematosus in NZM 2328 Mice
      Deficient in Discrete Pairs of BAFF Receptors.
AB  - OBJECTIVE: To determine the development of systemic lupus erythematosus (SLE) in
      NZM 2328 (NZM) mice deficient in 2 BAFF receptors. METHODS: NZM.BR-3(-/-) .BCMA(
      /-) , NZM.BR-3(-/-) .TACI(-/-) , and NZM.BCMA(-/-) .TACI(-/-) mice were evaluated
      on the clinical, pathologic, serologic, and cellular levels. BAFF receptor
      expression and lymphocyte phenotype were assessed by flow cytometry, IgG
      secreting cells by enzyme-linked immunospot assay, B cell responsiveness to BAFF
      and generation of Treg cells by in vitro culture, serum BAFF and total IgG and
      IgG autoantibody levels by enzyme-linked immunosorbent assay, renal
      immunopathology by immunofluorescence and histologic analyses, and clinical
      disease by assessment of proteinuria and mortality. RESULTS: Renal
      immunopathology and clinical disease were attenuated in NZM.BR-3(-/-) .BCMA(-/-)
      and NZM.BR-3(-/-) .TACI(-/-) mice but were accelerated in NZM.BCMA(-/-) .TACI(-/
      ) mice. Accelerated disease was associated with increases in B cells, IgG
      secreting cells, serum autoantibody levels, and T cells (especially CD4+
      activated memory cells), whereas attenuated disease was associated with
      reductions in many of these parameters. Serum BAFF levels were increased in all
      double-deficient NZM mice. Exogenous BAFF promoted the in vitro survival of B
      cells from NZM.BCMA(-/-) .TACI(-/-) or NZM wild-type mice but not those from
      NZM.BR-3(-/-) .BCMA(-/-) or NZM.BR-3(-/-) .TACI(-/-) mice. In vitro generation of
      Treg cells was reduced in NZM.BCMA(-/-) .TACI(-/-) mice, but not in NZM.BR-3(-/-)
      .BCMA(-/-) or NZM.BR-3(-/-) .TACI(-/-) mice. CONCLUSION: Elimination of B
      lymphocyte stimulator receptor 3 (BR-3) and TACI or BR-3 and BCMA inhibits the
      development of SLE in NZM mice. Selective targeting of BR-3 plus TACI or BR-3
      plus BCMA may be an efficacious therapeutic approach in human SLE.

PMID- 25989239
TI  - Statistical reporting in randomized controlled trials from the dermatology
      literature: a review of 44 dermatology journals.
AB  - BACKGROUND: The validity of randomized controlled trials (RCTs) is determined by
      several statistical factors. OBJECTIVES: To determine the level of recent
      statistical reporting in RCTs from the dermatology literature. METHODS: We
      searched MEDLINE for all RCTs published between 1 May 2013 and 1 May 2014 in 44
      dermatology journals. RESULTS: Two hundred and ten articles were screened, of
      which 181 RCTs from 27 journals were reviewed. Primary study outcomes were met in
      122 (67.4%) studies. Sample size calculations and beta values were reported in 52
      (28.7%) and 48 (26.5%) studies, respectively, and nonsignificant findings were
      supported in only 31 (17.1%). Alpha values were reported in 131 (72.4%) of
      studies with 45 (24.9%) having two-sided P-values, although adjustment for
      multiple statistical tests was performed in only 16 (9.9% of studies with >= two
      statistical tests performed). Sample size calculations were performed based on a
      single outcome in 44 (86.3%) and multiple outcomes in six (11.8%) studies.
      However, among studies that were powered for a single primary outcome, 20 (45.5%)
      made conclusions based on multiple primary outcomes. Twenty-one (41.2%) studies
      relied on secondary/unspecified outcomes. There were no differences for primary
      outcome being met (Chi-square, P = 0.29), sample size calculations (P >= 0.55),
      beta values (P = 0.89), alpha values (P = 0.65), correction for multiple
      statistical testing (P = 0.59), two-sided alpha (P = 0.64), support of
      nonsignificant findings (Fisher's exact, P = 0.23) based on the journal's impact
      factor. CONCLUSIONS: Levels of statistical reporting are low in RCTs from the
      dermatology literature. Future work is needed to improve these levels of
      reporting.

PMID- 25989240
TI  - Ultra high performance liquid chromatography with mass spectrometry method for
      the simultaneous determination of phenolic constituents in honey from various
      floral sources using multiwalled carbon nanotubes as extraction sorbents.
AB  - An ultra high performance liquid chromatography with mass spectrometry method has
      been developed for the simultaneous separation, identification and determination
      of 22 phenolic constituents in honey from various floral sources from Yemen.
      Solid-phase extraction was used for extraction of the target phenolic
      constituents from honey samples, while multiwalled carbon nanotubes were used as
      solid-phase adsorbent. The chromatographic separation of all phenolic
      constituents was performed on a BEH C18 column using a linear gradient elution
      with a binary mobile phase mixture of aqueous 0.1% formic acid and methanol. The
      quantitation was carried out in selected ion reaction monitoring acquisition
      mode. The total amount of phenolic acids, flavonoids and other phenols in each
      analyzed honey was found in the range of 338-3312, 122-5482 and 2.4-1342 MUg/100
      g of honey, respectively. 4-Hydroxybenzoic acid was found to be the major
      phenolic acid. The main detected flavonoid was chrysin, while cinnamic acid was
      found to be the major other phenol compound. The regeneration of solid phase
      adsorbent to be reused and recovery results confirm that the proposed method
      could be potentially used for the routine analysis of phenolic constituents in
      honey extract. 

PMID- 25989241
TI  - Effects of Cudrania tricuspidata Fruit Extract and Its Active Compound, 5,7,3',4'
      Tetrahydroxy-6,8-diprenylisoflavone, on the High-Affinity IgE Receptor-Mediated
      Activation of Syk in Mast Cells.
AB  - Cudrania tricuspidata fruit extract contains a rich source of prenylated
      flavonoids with potential antiatherosclerotic, hepatoprotective, and anti
      inflammatory properties. However, the effect of C. tricuspidata fruit extracts
      and its active compounds on the high-affinity IgE receptor (FcepsilonRI)-mediated
      signaling remains unknown. In the present study, the effect of methanol extract
      from the fruits of C. tricuspidata (MFC) and its active compound, 5,7,3',4'
      tetrahydroxy-6,8-diprenylisoflavone (THDPI), on FcepsilonRI-mediated signaling in
      mast cells was investigated. MFC and THDPI suppressed mast cell degranulation and
      Ca(2+) influx. MFC also interfered with IgE-FcepsilonRI interaction and decreased
      FcepsilonRIbeta mRNA expression in mast cells. Furthermore, MFC and THDPI
      inhibited the phosphorylation of Syk, LAT, and PLCgamma and F-actin
      redistribution. These results indicate that MFC and its active compound, THDPI,
      inhibit mast cell activation through the inhibition of FcepsilonRI-mediated Syk
      activation, suggesting a therapeutic potential for controlling mast cell
      activation in inflammatory and/or allergic processes. 

PMID- 25989243
TI  - Effects of Water on the Single-Chain Elasticity of Poly(U) RNA.
AB  - Water, the dominant component under the physiological condition, is a complicated
      solvent which greatly affects the properties of solute molecules. Here, we
      utilize atomic force microscope-based single-molecule force spectroscopy to study
      the influence of water on the single-molecule elasticity of an unstructured
      single-stranded RNA (poly(U)). In nonpolar solvents, RNA presents its inherent
      elasticity, which is consistent with the theoretical single-chain elasticity
      calculated by quantum mechanics calculations. In aqueous buffers, however, an
      additional energy of 1.88 kJ/mol.base is needed for the stretching of the ssRNA
      chain. This energy is consumed by the bound water rearrangement (Ew) during chain
      elongation. Further experimental results indicate that the Ew value is
      uncorrelated to the salt concentrations and stretching velocity. The results
      obtained in an 8 M guanidine.HCl solution provide more evidence that the bound
      water molecules around RNA give rise to the observed deviation between aqueous
      and nonaqueous environments. Compared to synthetic water-soluble polymers, the
      value of Ew of RNA is much lower. The weak interference of water is supposed to
      be the precondition for the RNA secondary structure to exist in aqueous solution.

PMID- 25989242
TI  - The cortical computations underlying feedback control in vocal production.
AB  - Recent neurophysiological studies of speaking are beginning to elucidate the
      neural mechanisms underlying auditory feedback processing during vocalizations.
      Here we review how research findings impact our state feedback control (SFC)
      model of speech motor control. We will discuss the evidence for cortical
      computations that compare incoming feedback with predictions derived from motor
      efference copy. We will also review observations from auditory feedback
      perturbation studies that demonstrate clear evidence for a state estimate
      correction process, which drives compensatory motor behavioral responses. While
      there is compelling support for cortical computations in the SFC model, there are
      still several outstanding questions that await resolution by future neural
      investigations. 

PMID- 25989244
TI  - Stabilizing Nanosized Si Anodes with the Synergetic Usage of Atomic Layer
      Deposition and Electrolyte Additives for Li-Ion Batteries.
AB  - A substantial increase in charging capacity over long cycle periods was made
      possible by the formation of a flexible weblike network via the combination of
      Al2O3 atomic layer deposition (ALD) and the electrolyte additive vinylene
      carbonate (VC). Transmission electron microscopy shows that a weblike network
      forms after cycling when ALD and VC were used in combination that dramatically
      increases the cycle stability for the Si composite anode. The ALD-VC combination
      also showed reduced reactions with the lithium salt, forming a more stable solid
      electrolyte interface (SEI) absent of fluorinated silicon species, as evidenced
      by X-ray photoelectron spectroscopy. Although the bare Si composite anode showed
      only an improvement from a 56% to a 45% loss after 50 cycles, when VC was
      introduced, the ALD-coated Si anode showed an improvement from a 73% to a 11%
      capacity loss. Furthermore, the anode with the ALD coating and VC had a capacity
      of 630 mAh g(-1) after 200 cycles running at 200 mA g(-1), and the bare anode
      without VC showed a capacity of 400 mAh g(-1) after only 50 cycles. This approach
      can be extended to other Si systems, and the formation of this SEI is dependent
      on the thickness of the ALD that affects both capacity and stability. 

PMID- 25989245
TI  - An emissive and pH switchable hydrazone-based hydrogel.
AB  - A serendipitous discovery has led to a new hydrazone-based low molecular weight
      fluorescent super-hydrogelator. The gelation and emission properties can be
      switched "ON" and "OFF" using pH, enabling the sensing of biogenic amines
      emanating from spoiled cod. 

PMID- 25989247
TI  - Development of a Novel Bidimensional Spectroelectrochemistry Cell Using Transfer
      Single-Walled Carbon Nanotubes Films as Optically Transparent Electrodes.
AB  - A really easy method to transfer commercial single-walled carbon nanotubes
      (SWCNTs) to different substrates is proposed. In this paper, a homogeneous
      transference of SWCNTs films to nonconductor and transparent supports, such as
      polyethylene terephthalate, glass, and quartz, and to conductor supports, such as
      indium tin oxide, aluminum, highly ordered pyrolytic graphite, and glassy carbon,
      was achieved using a very fast, reproducible, and clean methodology. In order to
      test these transferences, SWCNTs films transferred on quartz were used as working
      optically UV-vis transparent electrodes due to their optimal electrical and
      optical properties. A new easy-to-use, homemade optical fiber based cell for
      bidimensional spectroelectrochemistry was developed, offering the possibility to
      measure in normal and parallel configuration. The cell was tested with
      ferrocenemethanol, a compound widely used in electrochemistry but scarcely
      studied by spectroelectrochemistry, covering the UV-vis spectral region. 

PMID- 25989248
TI  - Wearable double-twisted fibrous perovskite solar cell.
AB  - Wearable double-twisted fibrous perovskite solar cells are developed based on
      flexible carbon nanotube fiber electrodes, which exhibit a maximum power
      conversion efficiency of 3.03% and bending stability larger than 1000 cycles, and
      maintain 89% efficiency after 96 h in ambient conditions if sealed by a
      transparent polymer layer. The obtained superior performance can shed light on
      future self-powering e-textiles. 

PMID- 25989246
TI  - Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in
      Rheumatoid Arthritis: A Meta-Analysis of Randomized Trials.
AB  - OBJECTIVE: The costs of biologic treatment per patient with rheumatoid arthritis
      (RA) are approximately 100 times the costs of treatment with a combination of
      conventional disease-modifying antirheumatic drugs (DMARDs). Despite this,
      biologic agents have not been proven superior. We compared the effects of
      combination DMARD therapies with and without biologic agents as therapy for
      patients with RA. METHODS: Eight randomized controlled trials published in 10
      articles were selected from a systematic literature search of 1,674 identified
      studies and integrated in a meta-analysis. These trials compared combinations of
      DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two
      reviewers independently entered data into standardized extraction forms. The
      combined effect measures were compared by means of the inverse variance method
      (continuous data) and the Mantel-Haenszel method (dichotomous data) using a
      random-effects model. RESULTS: The primary outcome, radiographic progression
      score, did not differ between the combination DMARD group and the TNF inhibitor
      group, neither during the second year (-0.09 units [-0.61, 0.44]) of treatment or
      during the first 2 years (0.66 units [-0.12, 1.43]). There were significant
      differences in the radiographic progression score, the American College of
      Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response
      criteria at 6 months in favor of TNF inhibitor treatment, but these differences
      were not present in patients treated with an initial steroid course and
      disappeared at 24 months, irrespective of the use of steroids. CONCLUSION: The
      difference between DMARD combination treatments, including or excluding TNF
      inhibitors, is small. Due to the enormous cost differences, RA guidelines should
      recommend combination DMARD treatment before initiation of TNF inhibitors.

PMID- 25989249
TI  - Estimating the effect of childhood socioeconomic disadvantage on oral cancer in
      India using marginal structural models.
AB  - BACKGROUND: Early life socioeconomic disadvantage could affect adult health
      directly or indirectly. To the best of our knowledge, there are no studies of the
      direct effect of early life socioeconomic conditions on oral cancer occurrence in
      adult life. METHODS: We conducted a multicenter, hospital-based, case-control
      study in India between 2011 and 2012 on 180 histopathologically confirmed
      incident oral and/or oropharyngeal cancer cases, aged 18 years or more, and 272
      controls that included hospital visitors, who were not diagnosed with any cancer
      in the same hospitals. Life-course data were collected on socioeconomic
      conditions, risk factors, and parental behavior through interview employing a
      life grid. The early life socioeconomic conditions measure was determined by
      occupation of the head of household in childhood. Adult socioeconomic measures
      included participant's education and current occupation of the head of household.
      Marginal structural models with stabilized inverse probability weights were used
      to estimate the controlled direct effects of early life socioeconomic conditions
      on oral cancer. RESULTS: The total effect model showed that those in the low
      socioeconomic conditions in the early years of childhood had 60% (risk ratio [RR]
      = 1.6 [95% confidence interval {CI} = 1.4, 1.9]) increased risk of oral cancer.
      From the marginal structural models, the estimated risk for developing oral
      cancer among those in low early life socioeconomic conditions was 50% (RR = 1.5
      [95% CI = 1.4, 1.5]), 20% (RR = 1.2 [95% CI = 0.9, 1.7]), and 90% (RR = 1.9 [95%
      CI = 1.7, 2.2]) greater than those in the high socioeconomic conditions when
      controlled for smoking, chewing, and alcohol, respectively. When all the three
      mediators were controlled in a marginal structural model, the RR was 1.3 (95% CI
      = 1.0, 1.6). CONCLUSION: Early life low socioeconomic condition had a controlled
      direct effect on oral cancer when smoking, chewing tobacco, and alcohol were
      separately adjusted in marginal structural models.

PMID- 25989251
TI  - Adaptive power-controllable orbital angular momentum (OAM) multicasting.
AB  - We report feedback-assisted adaptive multicasting from a single Gaussian mode to
      multiple orbital angular momentum (OAM) modes using a single phase-only spatial
      light modulator loaded with a complex phase pattern. By designing and optimizing
      the complex phase pattern through the adaptive correction of feedback
      coefficients, the power of each multicast OAM channel can be arbitrarily
      controlled. We experimentally demonstrate power-controllable multicasting from a
      single Gaussian mode to two and six OAM modes with different target power
      distributions. Equalized power multicasting, "up-down" power multicasting and
      "ladder" power multicasting are realized in the experiment. The difference
      between measured power distributions and target power distributions is assessed
      to be less than 1 dB. Moreover, we demonstrate data-carrying OAM multicasting by
      employing orthogonal frequency-division multiplexing 64-ary quadrature amplitude
      modulation (OFDM 64-QAM) signal. The measured bit-error rate curves and observed
      optical signal-to-noise ratio penalties show favorable operation performance of
      the proposed adaptive power-controllable OAM multicasting.

PMID- 25989250
TI  - Longitudinal in vivo evaluation of bone regeneration by combined measurement of
      multi-pinhole SPECT and micro-CT for tissue engineering.
AB  - Over the last decades, great strides were made in the development of novel
      implants for the treatment of bone defects. The increasing versatility and
      complexity of these implant designs request for concurrent advances in means to
      assess in vivo the course of induced bone formation in preclinical models. Since
      its discovery, micro-computed tomography (micro-CT) has excelled as powerful high
      resolution technique for non-invasive assessment of newly formed bone tissue.
      However, micro-CT fails to provide spatiotemporal information on biological
      processes ongoing during bone regeneration. Conversely, due to the versatile
      applicability and cost-effectiveness, single photon emission computed tomography
      (SPECT) would be an ideal technique for assessing such biological processes with
      high sensitivity and for nuclear imaging comparably high resolution (<1 mm).
      Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that
      release bone morphogenetic protein to guide the healing of critical sized
      calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and
      micro-CT evaluations we determine the spatiotemporal course of bone formation and
      remodeling within this synthetic hydrogel implant. End point evaluations by high
      resolution micro-CT and histological evaluation confirm the value of this
      approach to follow and optimize bone-inducing biomaterials. 

PMID- 25989252
TI  - Rapid Synthesis and Efficient Electrocatalytic Oxygen Reduction/Evolution
      Reaction of CoMn2O4 Nanodots Supported on Graphene.
AB  - Transition-metal oxides have attracted extensive interest as oxygen
      reduction/evolution reaction (ORR/OER) catalyst alternatives to precious Pt-based
      materials but generally exhibit limited electrocatalytic performance due to their
      large overpotential and low specific activity. We here report a rapid synthesis
      of spinel-type CoMn2O4 nanodots (NDs, below 3 nm) monodispersed on graphene for
      highly efficient electrocatalytic ORR/OER in 0.1 M KOH solution. The preparation
      of the composite involves the reaction of manganese and cobalt salts in mixed
      surfactant-solvent-water solution at mild temperature (120  degrees C) and air.
      CoMn2O4 NDs homogeneously distributed on carbonaceous substrates show strong
      coupling and facile charge transfer. Remarkably, graphene-supported CoMn2O4 NDs
      showed 20 mV higher ORR half-wave potential, twice the kinetic current, and
      better catalytic durability compared to the benchmark carbon-supported Pt
      nanoparticles (Pt/C). Moreover, CoMn2O4/reduced graphene oxide afforded
      electrocatalytic OER with a current density of 10 mA cm(-2) at a low potential of
      1.54 V and a small Tafel slope of ~56 mV/dec. This indicates that the composite
      of CoMn2O4 nanodots monodispersed on graphene is promising as highly efficient
      bifunctional electrocatalysts of ORR and OER that can be used in the areas of
      fuel cells and rechargeable metal-air batteries. 

PMID- 25989255
TI  - Electrical and Surface Properties of InAs/InSb Nanowires Cleaned by Atomic
      Hydrogen.
AB  - We present a study of InAs/InSb heterostructured nanowires by X-ray photoemission
      spectroscopy (XPS), scanning tunneling microscopy (STM), and in-vacuum electrical
      measurements. Starting with pristine nanowires covered only by the native oxide
      formed through exposure to ambient air, we investigate the effect of atomic
      hydrogen cleaning on the surface chemistry and electrical performance. We find
      that clean and unreconstructed nanowire surfaces can be obtained simultaneously
      for both InSb and InAs by heating to 380 +/- 20  degrees C under an H2 pressure 2
      * 10(-6) mbar. Through electrical measurement of individual nanowires, we observe
      an increase in conductivity of 2 orders of magnitude by atomic hydrogen cleaning,
      which we relate through theoretical simulation to the contact-nanowire junction
      and nanowire surface Fermi level pinning. Our study demonstrates the significant
      potential of atomic hydrogen cleaning regarding device fabrication when high
      quality contacts or complete control of the surface structure is required. As
      hydrogen cleaning has recently been shown to work for many different types of III
      V nanowires, our findings should be applicable far beyond the present materials
      system. 

PMID- 25989256
TI  - Nickel-Catalyzed Reactions Directed toward the Formation of Heterocycles.
AB  - Heterocycles have garnered significant attention because they are important
      functional building blocks in various useful molecules, such as pharmaceuticals,
      agricultural chemicals, pesticides, and materials. Several studies have been
      conducted regarding the preparation of heterocyclic skeletons with an emphasis on
      selectivity and efficiency. Three strategies are typically employed to construct
      cyclic molecules, namely, cyclization, cycloaddition, and ring-size alterations.
      Although each method has certain advantages, cycloaddition may be superior from
      the viewpoint of divergence. Specifically, cycloadditions enable the construction
      of rings from several pieces. However, the construction of heterocycles via
      cycloadditions is more challenging than the construction of carbocycles. For
      heterocycle construction, simple pericyclic reactions rarely work smoothly
      because of the large HOMO-LUMO gap unless well-designed combinations, such as
      electron-rich dienes and aldehydes, are utilized. Thus, a different approach
      should be employed to prepare heterocycles via cycloadditions. To this end, the
      use of metallacycles containing heteroatoms is expected to serve as a promising
      solution. In this study, we focused on the preparation of heteroatom-containing
      nickelacycles. Because nickel possesses a relatively high redox potential and an
      affinity for heteroatoms, several methods were developed to synthesize
      heteronickelacycles from various starting materials. The prepared nickelacycles
      were demonstrated to be reasonable intermediates in cycloaddition reactions,
      which were used to prepare various heterocycles. In this Account, we introduce
      the following four methods to prepare heterocycles via heteronickelacycles. (1)
      Direct oxidative insertion of Ni(0) to alpha,beta-unsaturated enone derivatives:
      treatment of 3-ethoxycarbonyl-4-phenyl-3-buten-2-one with Ni(0) afforded an oxa
      nickelacycle, which reacted with alkynes to give pyrans. (2) Substitution of a
      part of a cyclic compound with low-valent nickel, accompanied by elimination of
      small molecules such as CO, CO2, and acetophenone: treatment of phthalic
      anhydride with Ni(0) in the presence of ZnCl2 afforded the oxanickelacycle, which
      was formed via decarbonylative insertion of Ni(0) and reacted with alkynes to
      give isocumarins. (3) Cyclization to a nickelacycle, accompanied by two C-C sigma
      bond activations: insertion of Ni(0) into an arylnitrile, followed by aryl
      cyanation of an alkyne, gave alkenylnickel as an intermediate. The alkenylnickel
      species subsequently underwent an intramolecular nucleophilic attack with an
      arylcarbonyl group to form a cyclized product with concomitant cleavage of the C
      C sigma-bond between the carbonyl and aryl groups. (4) Assembly of several
      components to form a heteroatom-containing nickelacycle via cycloaddition: a new
      [2 + 2 + 1] cyclization reaction was carried out using an alpha,beta-unsaturated
      ester, isocyanate, and alkyne via a nickelacycle. On the basis of these four
      strategies, we developed new methods to prepare heterocyclic compounds using
      nickelacycles as the key active species. 

PMID- 25989253
TI  - Cervical cancer screening and follow-up in 4 geographically diverse US health
      care systems, 1998 through 2007.
AB  - BACKGROUND: Cervical cancer screening and follow-up guidelines have changed
      considerably in recent years, but to the authors' knowledge few published reports
      exist to estimate the impact of these changes in community-based settings. The
      authors examined the patterns and results of cervical cancer testing and follow
      up over a decade in 4 geographically diverse US health care systems to inform the
      future evaluation of changes resulting from increased uptake of the human
      papillomavirus (HPV) vaccination. METHODS: The authors studied women aged 21 to
      65 years who were members of one of these health systems at any time between 1998
      and 2007. Data were collected and standardized across sites, based on receipt of
      Papanicolaou (Pap) and HPV tests, HPV vaccination, cervical biopsies, and
      treatment of cervical dysplasia. Annual rates (per 1000 person-years) of Pap
      testing, HPV testing, and cervical biopsy and treatment procedures were
      calculated. Screening intervals and trends in the results of screening Pap tests
      and cervical biopsies also were examined. RESULTS: Pap testing rates decreased
      (from 483 per 1000 person-years in 2000 to 412 per 1000 person-years in 2007) and
      HPV testing rates increased over the study period. Screening frequency varied
      across health care systems, and many women continued to receive annual testing.
      All 4 sites moved to less frequent screening over the study period without marked
      changes in the overall use of cervical biopsy or treatment. CONCLUSIONS: Despite
      differences over time and across health plans in rates of cervical cancer testing
      and follow-up cervical procedures, the authors found no notable differences in
      Pap test results, diagnostic or treatment procedure rates, or pathological
      outcomes. This finding suggests that the longer screening intervals did not lead
      to more procedures or more cancer diagnoses.

PMID- 25989254
TI  - A pair of light signaling factors FHY3 and FAR1 regulates plant immunity by
      modulating chlorophyll biosynthesis.
AB  - Light and chloroplast function is known to affect the plant immune response;
      however, the underlying mechanism remains elusive. We previously demonstrated
      that two light signaling factors, FAR-RED ELONGATED HYPOCOTYL 3 (FHY3) and FAR
      RED IMPAIRED RESPONSE 1 (FAR1), regulate chlorophyll biosynthesis and seedling
      growth via controlling HEMB1 expression in Arabidopsis thaliana. In this study,
      we reveal that FHY3 and FAR1 are involved in modulating plant immunity. We showed
      that the fhy3 far1 double null mutant displayed high levels of reactive oxygen
      species and salicylic acid (SA) and increased resistance to Pseudomonas syringae
      pathogen infection. Microarray analysis revealed that a large proportion of
      pathogen-related genes, particularly genes encoding nucleotide-binding and
      leucine-rich repeat domain resistant proteins, are highly induced in fhy3 far1.
      Genetic studies indicated that the defects of fhy3 far1 can be largely rescued by
      reducing SA signaling or blocking SA accumulation, and by overexpression of
      HEMB1, which encodes a 5-aminolevulinic acid dehydratase in the chlorophyll
      biosynthetic pathway. Furthermore, we found that transgenic plants with reduced
      expression of HEMB1 exhibit a phenotype similar to fhy3 far1. Taken together,
      this study demonstrates an important role of FHY3 and FAR1 in regulating plant
      immunity, through integrating chlorophyll biosynthesis and the SA signaling
      pathway. 

PMID- 25989257
TI  - A comparative study of ballpoint ink ageing parameters using GC/MS.
AB  - For more than a decade scientists tried to develop methods capable of dating ink
      by monitoring the loss of phenoxyethanol (PE) over time. While many methods were
      proposed in the literature, few were really used to solve practical cases and
      they still raise much concern within the scientific community. In fact, due to
      the complexity of ink drying processes it is particularly difficult to find a
      reliable ageing parameter to reproducibly follow ink ageing. Moreover, systematic
      experiments are required in order to evaluate how different factors actually
      influence the results over time. Therefore, this work aimed at evaluating the
      capacity of four different ageing parameters to reliably follow ink ageing over
      time: (1) the quantity of solvent PE in an ink line, (2) the relative peak area
      (RPA) normalising the PE results using stable volatile compounds present in the
      ink formulation, (3) the solvent loss ratio (R%) calculated from PE results
      obtained by the analyses of naturally and artificially aged samples, (4) a
      modified solvent loss ratio version (R%*) calculated from RPA results. After the
      determination of the limits of reliable measurements of the analytical method,
      the repeatability of the different ageing parameters was evaluated over time, as
      well as the influence of ink composition, writing pressure and storage conditions
      on the results. Surprisingly, our results showed that R% was not the most
      reliable parameter, as it showed the highest standard deviation. Discussion of
      the results in an ink dating perspective suggests that other proposed parameters,
      such as RPA values, may be more adequate to follow ink ageing over time. 

PMID- 25989258
TI  - Community teaching hospital surgical experience with adult intussusception: Study
      of nine cases and literature review.
AB  - INTRODUCTION: Although more commonly thought of as a surgical problem affecting
      children, surgeons evaluating the adult acute abdomen should remain vigilante in
      diagnosing intussusception. In this case series, we reviewed 6 years of medical
      records at a community teaching hospital in order to analyze the etiology,
      presentation, and management of nine cases of adult intussusception. PRESENTATION
      OF CASES: Most of the patients in our series shared symptoms of nausea, vomiting,
      and abdominal pain. Computed tomography scan was crucial in distinguishing adult
      intussusception from other causes of acute abdomen. Eight patients underwent
      operative exploration, five of whom underwent bowel resection. One patient's
      symptoms resolved with no surgical intervention. All nine patients had excellent
      outcomes. DISCUSSION: Although detailed history and physical examination are
      essential in all cases of acute abdomen, CT scan findings of "target" signs are
      pathognomonic of intussusception. Laparoscopy should be strongly considered in
      select cases. Current literature suggests that reduction may be performed before
      resection if the lesion meets certain stringent parameters. The primary concern
      with regards to reduction before resection is potential embolization of malignant
      cells. Colonic intussusception is almost always treated with resection without
      reduction, while small intestinal intussusception could be treated by reduction
      before resection, if the small bowel lead points are less likely to be malignant.
      CONCLUSION: Intussusception is a rare but serious etiology of the acute abdomen
      in adults. Each case should be evaluated independently according to the specific
      type of lead-point lesion. Excellent outcomes may be anticipated with prompt
      diagnosis and surgical treatment.

PMID- 25989259
TI  - The management of bilateral myelolipoma: Case report and review of the
      literature.
AB  - INTRODUCTION: Bilateral adrenal myelolipoma is a rare benign neoplasm. We
      presented the case of a young man affected by a bilateral myelolipoma and the
      analysis of the literature of bilateral cases of myelolipoma. Our purpose is to
      give a suggestion of clear terms of reference regarding the management of this
      kind of bilateral neoplasm. PRESENTATION OF CASE: We reported the case of a 41
      year-old healthy man complained of abdominal pain in the upper quadrants. No
      significant alterations were found in routine blood and endocrinological tests.
      The imaging (CT and MRI) showed a huge right adrenal mass and a smaller lesion at
      the left adrenal gland. The preoperative pathological characterization was
      suggestive for a myelolipoma. A right open adrenalectomy was performed, and a
      radiological surveillance was planned for the left tumor. The pathological exam
      confirmed the diagnosis. DISCUSSION: In literature, there are 36 cases described.
      The clinical presentation consisted of symptomatic tumors, incidentally diagnosed
      lesions or myelolipomas in patients with an associated endocrinal disorder.
      Symptomatic tumors or those bigger than 7cm, because of the potential risk of
      rupture, are usually treated surgically. In smaller (<7cm) and asymptomatic ones
      the surgical treatment is not univocal. CONCLUSION: In the setting of the
      surgical treatment, it is important to preserve in some way the hormonal
      function. For that reason, the bilateral adrenalectomy has to be reserved for
      symptomatic or sizeable (>7cm) cases. As far as we know, this is the first review
      on bilateral myelolipomas.

PMID- 25989261
TI  - Infant mental health and attachment.

PMID- 25989260
TI  - Impact of activated carbon on the catabolism of (14)C-phenanthrene in soil.
AB  - Activated carbon amendment to contaminated soil has been proposed as an
      alternative remediation strategy to the management of persistent organic
      pollutant in soils and sediments. The impact of varying concentrations (0%,
      0.01%, 0.1% and 1.0%) of different types of AC on the development of phenanthrene
      catabolism in soil was investigated. Mineralisation of (14)C-phenanthrene was
      measured using respirometric assays. The increase in concentration of CB4, AQ5000
      or CP1 in soil led to an increase in the length of the lag phases. Statistical
      analyses showed that the addition of increasing concentrations of AC to the soil
      significantly reduced (P < 0.05) the extent of (14)C-phenanthrene mineralisation.
      For example, for CB4-, AQ5000- and CP1-amended soils, the overall extent of (14)C
      phenanthrene mineralisation reduced from 43.1% to 3.28%, 36.9% to 0.81% and 39.6%
      to 0.96%, respectively, after 120 days incubation. This study shows that the
      properties of AC, such as surface area, pore volume and particle size, are
      important factors in controlling the kinetics of (14)C-phenanthrene
      mineralisation in soil. 

PMID- 25989262
TI  - Factors affecting medication adherence in children receiving outpatient
      pharmacotherapy and parental adherence.
AB  - PROBLEM: Although pharmacotherapy is an effective treatment for many psychiatric
      disorders in children and adolescents, medication adherence rates among children
      are low. This study clarifies factors affecting children's medication adherence
      and the role of parental involvement. METHOD: Patients aged 7-17 years with a
      history of psychotropic medication treatment and their mothers were included in
      this study. Each mother and child completed self-administered questionnaires.
      Thirty mother-child pairs who fully completed the questionnaires were included in
      the analysis. RESULTS: Medication adherence was greater in children and mothers
      when mothers felt that "children's symptoms improved with treatment and
      medication." Medication adherence in children and mothers significantly
      correlated with the child's reported trust in their parent. CONCLUSIONS: The
      results suggest the need for psychosocial support that considers the influence of
      mothers on medication adherence in children treated in child psychiatry
      departments.

PMID- 25989263
TI  - Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney
      Transplants Using Extended Criteria Donors During Acute T Cell-Mediated
      Rejection.
AB  - Although renal transplantation using expanded criteria donors has become a common
      practice, immune responses related to immunosenescence in those kidney allografts
      have not been studied yet in humans. We performed a retrospective molecular
      analysis of the T cell immune response in 43 kidney biopsies from patients with
      acute T cell-mediated rejection including 25 from recipients engrafted with a
      kidney from expanded criteria donor and 18 from recipients grafted with optimal
      kidney allograft. The clinical, transplant and acute T cell-mediated rejection
      characteristics of both groups were similar at baseline. The expression of
      RORgammat, Il-17 and T-bet mRNA was significantly higher in the elderly than in
      the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA
      levels were significantly higher in elderly patients experiencing successful
      acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA
      was strongly associated with nonsuccessful reversal in elderly patients (p =
      0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3
      expression experienced significantly more treatment failure (87.5%) than patients
      with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p =
      0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and
      prognosis of acute T cell-mediated rejection in recipients of expanded criteria
      allograft.

PMID- 25989264
TI  - Estimated deaths and illnesses averted during fungal meningitis outbreak
      associated with contaminated steroid injections, United States, 2012-2013.
AB  - During 2012-2013, the US Centers for Disease Control and Prevention and partners
      responded to a multistate outbreak of fungal infections linked to
      methylprednisolone acetate (MPA) injections produced by a compounding pharmacy.
      We evaluated the effects of public health actions on the scope of this outbreak.
      A comparison of 60-day case-fatality rates and clinical characteristics of
      patients given a diagnosis on or before October 4, the date the outbreak was
      widely publicized, with those of patients given a diagnosis after October 4
      showed that an estimated 3,150 MPA injections, 153 cases of meningitis or stroke,
      and 124 deaths were averted. Compared with diagnosis after October 4, diagnosis
      on or before October 4 was significantly associated with a higher 60-day case
      fatality rate (28% vs. 5%; p<0.0001). Aggressive public health action resulted in
      a substantially reduced estimated number of persons affected by this outbreak and
      improved survival of affected patients. 

PMID- 25989265
TI  - Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by
      Modulating B Cell Migration and Germinal Center Formation.
AB  - OBJECTIVE: Syndecan 4 has been implicated as a critical mediator of inflammatory
      responses because of its functions as a coreceptor and reservoir for growth
      factors and chemokines. Although syndecan 4 is known to be expressed on B cells,
      its role in immune responses remains unclear. The purpose of this study was to
      investigate the contribution of syndecan 4 to the development of immune arthritis
      in murine models. METHODS: The clinical severity of 3 immunopathologically
      distinct models, collagen-induced arthritis (CIA), antigen-induced arthritis
      (AIA), and collagen antibody-induced arthritis (CAIA), was evaluated in wild-type
      (WT) mice and in syndecan 4-deficient (Sdc4(-/-) ) mice. Germinal center (GC)
      formation, B cell profiles, humoral immune responses, and B cell migration were
      analyzed during the course of CIA. RESULTS: Sdc4(-/-) mice were resistant to the
      induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which
      are T cell dependent and T cell independent, respectively, occurred with equal
      frequency in WT mice and Sdc4(-/-) mice. Furthermore, Sdc4(-/-) mice had reduced
      numbers of B cells and deficient GC formation in draining lymph nodes (DLNs)
      during the course of CIA, resulting in reduced production of collagen-specific
      autoantibodies. Compared with B cells from WT mice, B cells from Sdc4(-/-) mice
      showed reduced chemotactic migration toward stromal cell-derived factor 1 (SDF-1)
      and reduced SDF-1-mediated Akt phosphorylation. Consistent with these findings,
      in vivo transfer experiments showed that fewer Sdc4(-/-) B cells than WT B cells
      were found in and around the follicles in the DLNs. CONCLUSION: Our findings
      suggest that syndecan 4 contributes to the development of CIA by promoting GC
      formation and autoantibody production through its regulation of SDF-1-mediated B
      cell migration.

PMID- 25989266
TI  - Congenital nevi versus metastatic melanoma in a newborn to a mother with
      malignant melanoma - diagnosis supported by sex chromosome analysis and Imaging
      Mass Spectrometry.
AB  - A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on
      her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm
      thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no
      ulceration. Following induction of labor, the patient underwent re-excision with
      sentinel lymph node biopsy. This showed no residual melanoma and no lymph node
      metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of
      which were large and irregular. Two were biopsied and histologic examination
      showed dense dermal proliferation of medium sized melanocytes with multiple
      mitotic figures and no maturation with their descent into the dermis, raising
      suspicion of transplacental metastases. Examination of the placenta failed to
      show metastatic lesions. Multiplex polymerase chain reaction (PCR)-based
      genotyping, including testing for amelogenin locus for sex chromosome
      determination, demonstrated the presence of Y chromosome material in the
      melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of
      congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis
      of the mother's lesion showed proteomic signature expression indicative of
      malignant melanoma, whereas the two lesions in the newborn showed changes
      indicative of nevi. This case demonstrates the utility of genotyping and Mass
      Spectrometry analysis in this challenging clinical scenario. 

PMID- 25989267
TI  - Atraumatic restorative technique: case report on dental management of a patient
      with Moebius syndrome.
AB  - BACKGROUND: Clinical challenges associated with Moebius syndrome, a rare
      congenital neuromuscular disorder, include orofacial anomalies like microstomia,
      limited mouth opening and severe gag reflex. METHODS: This case report presents
      the dental management of an anxious female with Moebius syndrome. For
      restorations, atraumatic restorative technique (ART), using glass ionomer cement
      was used with hand instruments. RESULTS: All necessary dental treatment was
      completed in the dental chair, thus avoiding the need for a general anaesthetic,
      and associated complications with airway management due to orofacial
      abnormalities. CONCLUSIONS: ART is an appropriate technique for people with
      microstomia and/or limited mouth opening, such as those with Moebius syndrome.
      The application of ART can be extended to other special needs patients (people
      with physical and intellectual disabilities, extreme anxiety, needle phobia and
      the frail elderly in aged care facilities), where access or cooperation is
      difficult or limited.

PMID- 25989268
TI  - Post-diagnostic oral bisphosphonate use and colorectal cancer mortality: a
      population-based cohort study within the UK Clinical Practice Research Datalink.
AB  - BACKGROUND: We conducted the first study to investigate post-diagnostic oral
      bisphosphonates use and colorectal cancer-specific mortality. METHODS: Colorectal
      cancer patients were identified from the National Cancer Data Repository (1998
      2007) and linked to the UK Clinical Practice Research Datalink, providing
      prescription records, and Office of National Statistics mortality data. Time
      dependent Cox regression models investigated colorectal cancer-specific mortality
      in post-diagnostic bisphosphonate users. RESULTS: Overall, in 4791 colorectal
      cancer patients, there was no evidence of an association between bisphosphonate
      use and colorectal cancer-specific mortality (adjusted hazard ratio=1.11; 95%
      confidence interval 0.80, 1.54) or with drug frequency or type. CONCLUSIONS: In
      this novel population-based cohort study, post-diagnostic bisphosphonate use was
      not associated with longer rates of colorectal cancer survival.

PMID- 25989269
TI  - Long-term adverse outcomes in survivors of childhood bone sarcoma: the British
      Childhood Cancer Survivor Study.
AB  - BACKGROUND: With improved survival, more bone sarcoma survivors are approaching
      middle age making it crucial to investigate the late effects of their cancer and
      its treatment. We investigated the long-term risks of adverse outcomes among 5
      year bone sarcoma survivors within the British Childhood Cancer Survivor Study.
      METHODS: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs)
      were investigated for 664 bone sarcoma survivors. Use of health services, health
      and marital status, alcohol and smoking habits, and educational qualifications
      were investigated for survivors who completed a questionnaire. RESULTS: Survivors
      were seven times more likely to experience all-cause mortality than expected, and
      there were substantial differences in risk depending on tumour type. Beyond 25
      years follow-up the risk of dying from all-causes was comparable to the general
      population. This is in contrast to dying before 25 years where the risk was 12.7
      fold that expected. Survivors were also four times more likely to develop a SPN
      than expected, where the excess was restricted to 5-24 years post diagnosis.
      Increased health-care usage and poor health status were also found. Nonetheless,
      for some psychosocial outcomes survivors were better off than expected.
      CONCLUSIONS: Up to 25 years after 5-year survival, bone sarcoma survivors are at
      substantial risk of death and SPNs, but this is greatly reduced thereafter. As
      95% of all excess deaths before 25 years follow-up were due to recurrences and
      SPNs, increased monitoring of survivors could prevent mortality. Furthermore,
      bone and breast SPNs should be a particular concern. Since there are variations
      in the magnitude of excess risk depending on the specific adverse outcome under
      investigation and whether the survivors were initially diagnosed with
      osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these
      factors. These findings should provide useful evidence for risk stratification
      and updating clinical follow-up guidelines.

PMID- 25989270
TI  - Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS
      mutated metastatic colorectal cancer.
AB  - BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway has been
      implicated in the molecular pathogenesis of human cancers, including metastatic
      colorectal cancer (mCRC). This provides a rationale for the development of MAPK
      targeted agents such as pimasertib. METHODS: Patients with KRAS mutant mCRC were
      treated in the second-line setting with FOLFIRI (5-fluorouracil/folinic
      acid/irinotecan) plus pimasertib. The primary objective of the safety run-in
      phase was to determine the maximum-tolerated dose (MTD) and the recommended phase
      II dose of pimasertib combined with FOLFIRI. RESULTS: Sixteen patients were
      enrolled in the trial. Ten and six patients were treated daily with 45 and 60 mg
      of pimasertib plus FOLFIRI, respectively. The MTD was considered to be 45 mg per
      day. The most common treatment-emergent adverse events were diarrhoea, nausea,
      vomiting, asthenia and skin/rash event. Of the 15 patients in the efficacy
      analysis group, two patients had partial response, nine patients had stable
      disease, three patients had progressive disease as their best overall response
      and one patient could not be evaluated. CONCLUSIONS: Dose escalation of
      pimasertib in combination with FOLFIRI was limited by toxicity. At the MTD of 45
      mg per day, pimasertib was adequately tolerated in patients with mCRC and no
      unexpected or new safety signals or concerns were identified.

PMID- 25989271
TI  - Texture analysis of (125)I-A5B7 anti-CEA antibody SPECT differentiates metastatic
      colorectal cancer model phenotypes and anti-vascular therapy response.
AB  - BACKGROUND: We aimed to test the ability of texture analysis to differentiate the
      spatial heterogeneity of (125)I-A5B7 anti-carcinoembryonic antigen antibody
      distribution by nano-single photon emission computed tomography (SPECT) in well
      differentiated (SW1222) and poorly differentiated (LS174T) hepatic metastatic
      colorectal cancer models before and after combretastatin A1 di-phosphate anti
      vascular therapy. METHODS: Nano-SPECT imaging was performed following tail vein
      injection of 20 MBq (125)I-A5B7 in control CD1 nude mice (LS174T, n=3 and SW1222,
      n=4), and CA1P-treated mice (LS174T, n=3; SW1222, n=4) with liver metastases.
      Grey-level co-occurrence matrix textural features (uniformity, homogeneity,
      entropy and contrast) were calculated in up to three liver metastases in 14 mice
      from control and treatment groups. RESULTS: Before treatment, the LS174T
      metastases (n=7) were more heterogeneous than SW1222 metastases (n=12)
      (uniformity, P=0.028; homogeneity, P=0.01; contrast, P=0.045). Following CA1P,
      LS174T metastases (n=8) showed less heterogeneity than untreated LS174T controls
      (uniformity, P=0.021; entropy, P=0.006). Combretastatin A1 di-phosphate-treated
      SW1222 metastases (n=11) showed no difference in texture features compared with
      controls (all P>0.05). CONCLUSIONS: Supporting the potential for novel imaging
      biomarkers, texture analysis of (125)I-A5B7 SPECT shows differences in spatial
      heterogeneity of antibody distribution between well-differentiated (SW1222) and
      poorly differentiated (LS174T) liver metastases before treatment. Following anti
      vascular treatment, LS174T metastases, but not SW1222 metastases, were less
      heterogeneous.

PMID- 25989272
TI  - Expression of E-cadherin repressors SNAIL, ZEB1 and ZEB2 by tumour and stromal
      cells influences tumour-budding phenotype and suggests heterogeneity of stromal
      cells in pancreatic cancer.
AB  - BACKGROUND: There is evidence that tumour-stroma interactions have a major role
      in the neoplastic progression of pancreatic ductal adenocarcinoma (PDAC). Tumour
      budding is thought to reflect the process of epithelial-mesenchymal transition
      (EMT); however, the relationship between tumour buds and EMT remains unclear.
      Here we characterize the tumour-budding- and stromal cells in PDAC at protein and
      mRNA levels concerning factors involved in EMT. METHODS: mRNA in situ
      hybridisation and immunostaining for E-cadherin, beta-catenin, SNAIL1, ZEB1,
      ZEB2, N-cadherin and TWIST1 were assessed in the main tumour, tumour buds and
      tumour stroma on multipunch tissue microarrays from 120 well-characterised PDACs
      and associated with the clinicopathological features, including peritumoural
      (PTB) and intratumoural (ITB) budding. RESULTS: Tumour-budding cells showed
      increased levels of ZEB1 (P<0.0001) and ZEB2 (P=0.0119) and reduced E-cadherin
      and beta-catenin (P<0.0001, each) compared with the main tumour. Loss of
      membranous beta-catenin in the main tumour (P=0.0009) and tumour buds (P=0.0053),
      without nuclear translocation, as well as increased SNAIL1 in tumour and stromal
      cells (P=0.0002, each) correlated with high PTB. ZEB1 overexpression in the main
      tumour-budding and stromal cells was associated with high ITB (P=0.0084; 0.0250
      and 0.0029, respectively) and high PTB (P=0.0005; 0.0392 and 0.0007,
      respectively). ZEB2 overexpression in stromal cells correlated with higher pT
      stage (P=0.03), lymphatic invasion (P=0.0172) and lymph node metastasis
      (P=0.0152). CONCLUSIONS: In the tumour microenvironment of phenotypically
      aggressive PDAC, tumour-budding cells express EMT hallmarks at protein and mRNA
      levels underlining their EMT-type character and are surrounded by stromal cells
      expressing high levels of the E-cadherin repressors ZEB1, ZEB2 and SNAIL1, this
      being strongly associated with the tumour-budding phenotype. Moreover, our
      findings suggest the existence of subtypes of stromal cells in PDAC with
      phenotypical and functional heterogeneity.

PMID- 25989273
TI  - Validation of histomolecular classification utilizing histological subtype, MUC1,
      and CDX2 for prognostication of resected ampullary adenocarcinoma.
AB  - BACKGROUND: Outcomes for ampullary adenocarcinomas are heterogeneous, and
      numerous methods of categorisation exist. A histomolecular phenotype based on
      histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and
      Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We
      attempt to validate this classification in a large patient population. METHODS:
      Tissue samples from 163 patients with resected ampullary adenocarcinoma were
      classified based on histology and immunohistochemical expression of CDX2 and
      MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a
      sample with pancreaticobiliary histology, positive MUC1 and negative CDX2
      expression. RESULTS: There were 82 deaths; median follow-up of 32.4 months; and
      median overall survival of 87.7 (95% CI 42.9-109.5) months. PB comprised 28.2% of
      the cases. Factors associated with overall survival were histological subtype
      (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular
      (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT)
      vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was
      statistically significant, although MUC1 positivity defined as ?10% staining was
      significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR
      2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival.
      CONCLUSIONS: The prognostic ability of histomolecular phenotype has been
      validated in an independent cohort of ampullary adenocarcinoma patients.

PMID- 25989274
TI  - PTEN loss is associated with follicular variant of Middle Eastern papillary
      thyroid carcinoma.
AB  - BACKGROUND: PTEN gene at chromosomes 10q23.3 is a tumour suppressor gene that is
      inactivated in many types of human cancers. The known mechanisms of PTEN
      inactivation are rendered to mutation, epigenetic silencing by aberrant
      methylation or gene deletion. Although PTEN role has been documented in many
      cancers, PTEN alteration in papillary thyroid carcinoma (PTC) has not been fully
      elucidated. The aim of this study is to comprehensively investigate PTEN
      alterations in a large cohort of Middle Eastern papillary thyroid cancer by
      immunohistochemistry and fluorescent in situ hybridisation (FISH). METHODS: PTEN
      protein expression was analysed by immunohistochemistry in a tissue microarray
      (TMA) format in a large cohort of more than 1000 patients with papillary thyroid
      cancer. Copy number changes in PTEN were analysed by FISH and data were
      correlated with clinicopathological parameters along with survival analysis.
      RESULTS: PTEN inactivation reflected by complete absence of staining was seen in
      24.5% of PTC samples, whereas PTEN deletion was seen only in 4.8% of the tested
      samples by FISH. No association was seen between PTEN loss of protein expression
      and PTEN gene deletion. However, interestingly, PTEN loss of expression was
      significantly associated with the follicular variant subset of papillary thyroid
      cancer. CONCLUSION: Our study confirmed that PTEN might have a role in
      pathogenesis in a subset of PTC. PTEN loss of protein expression is a more common
      event in follicular variant of papillary thyroid cancer. Lack of association
      between PTEN loss of protein expression and PTEN gene deletion might indicate
      that gene deletion may not be the sole cause for PTEN loss of expression and
      these results might raise the possibility of other mechanism such as promoter
      methylation-mediated gene silencing to be responsible for PTEN inactivation.

PMID- 25989275
TI  - KPNA2 is a nuclear export protein that contributes to aberrant localisation of
      key proteins and poor prognosis of breast cancer.
AB  - BACKGROUND: It is recognised that modulations of the nuclear import of
      macromolecules have a role in changing cellular phenotypes and carcinogenesis. We
      and others have noticed that aberrant subcellular localisation of DNA damage
      response (DDR) proteins in breast cancer (BC) is associated with loss-of-function
      phenotype. This study aims to investigate the biological and clinical
      significance of the nucleocytoplasmic transport protein karyopherin alpha-2
      (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC.
      METHODS: A large (n=1494) and well-characterised series of early-stage invasive
      BC with a long-term follow-up was assessed for KPNA2 protein by using
      immunohistochemistry. RESULTS: KPNA2 expression was associated with the
      subcellular localisation of key DDR proteins that showed cytoplasmic expression
      including BRCA1, RAD51, SMC6L1, gammaH2AX, BARD1, UBC9, PIAS1 and CHK1. High
      level of KPNA2 was associated not only with cytoplasmic localisation of these
      proteins but also with their low/negative nuclear expression. Positive KPNA2
      expression was associated with negative oestrogen receptor and triple-negative
      phenotype. Survival analysis showed that KPNA2 was associated with poor outcome
      (P<0.0001), but this effect was not independent of other prognostic variables.
      CONCLUSIONS: This study provides further evidence for the complexity of DDR
      mechanism in BC, and that KNPA2 has a role in the aberrant subcellular
      localisation of DDR proteins with subsequent impaired function.

PMID- 25989277
TI  - Comment on: 'evaluation of chemoresponse assays as predictive markers'.

PMID- 25989276
TI  - Vitamin E intake from natural sources and head and neck cancer risk: a pooled
      analysis in the International Head and Neck Cancer Epidemiology consortium.
AB  - BACKGROUND: Evidence for the possible effect of vitamin E on head and neck
      cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10
      case-control studies (5959 cases and 12 248 controls) participating in the
      International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess
      the association between vitamin E intake from natural sources and cancer of the
      oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated using unconditional logistic regression models
      applied to quintile categories of non-alcohol energy-adjusted vitamin E intake.
      RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR
      for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend
      <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001).
      There was, however, appreciable heterogeneity of the estimated effect across
      studies for oral/pharyngeal cancer. Inverse associations were generally observed
      for the anatomical subsites of oral and pharyngeal cancer and within covariate
      strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E
      intake from foods may lower HNC risk, although we were not able to explain the
      heterogeneity observed across studies or rule out certain sources of bias.

PMID- 25989278
TI  - Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti
      EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer.
AB  - BACKGROUND: Metastatic colorectal cancer (mCRC) that harbours a BRAF V600E
      mutation (BRAF MT) is associated with poorer outcomes. However, whether this
      mutation is predictive of treatment benefit from anti-epidermal growth factor
      receptor (EGFR) monoclonal antibodies (mAbs) is uncertain. METHODS: We conducted
      a systematic review and meta-analysis of randomised controlled trials (RCTs)
      published up to July 2014 that evaluated the effect of BRAF MT on the treatment
      benefit from anti-EGFR mAbs for mCRC. RESULTS: Seven RCTs met the inclusion
      criteria for assessment of overall survival (OS), whereas eight RCTs met the
      inclusion criteria for assessment of progression-free survival (PFS). For RAS
      WT/BRAF MT tumours, the hazard ratio for OS benefit with anti-EGFR mAbs was 0.97
      (95% CI; 0.67-1.41), whereas the hazard ratio was 0.81 (95% CI; 0.70-0.95) for
      RAS WT/BRAF WT tumours. However, the test of interaction (P=0.43) was not
      statistically significant, highlighting that the observed differences in the
      effect of anti-EGFR mAbs on OS according to the BRAF mutation status may be due
      to chance alone. Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was
      0.86 (95% CI; 0.61-1.21) for RAS WT/BRAF MT tumours as compared with 0.62 (95%
      CI; 0.50-0.77) for RAS WT/BRAF WT tumours (test of interaction, P=0.07).
      INTERPRETATION: This meta-analysis demonstrates that there is insufficient
      evidence to definitively state that RAS WT/BRAF MT individuals attain a different
      treatment benefit from anti-EGFR mAbs for mCRC compared with RAS WT/BRAF WT
      individuals. As such, there are insufficient data to justify the exclusion of
      anti-EGFR mAb therapy for patients with RAS WT/BRAF MT mCRC.

PMID- 25989279
TI  - Seroconversions to Rickettsiae in US Military Personnel in South Korea.

PMID- 25989280
TI  - Methotrexate Treatment for Cesarean Scar Ectopic Pregnancy: Learning Lessons.

PMID- 25989281
TI  - Reply to Letter to the Editor: Methotrexate Treatment for Cesarean Scar Ectopic
      Pregnancy: Learning Lessons.

PMID- 25989283
TI  - Modulation of the pre-supplementary motor area reduces the sense of agency
      (Commentary on Cavazzana et al.).

PMID- 25989282
TI  - Endotoxin-induced skeletal muscle wasting is prevented by angiotensin-(1-7)
      through a p38 MAPK-dependent mechanism.
AB  - Skeletal muscle atrophy induced during sepsis syndrome produced by endotoxin in
      the form of LPS (lipopolysaccharide), is a pathological condition characterized
      by the loss of strength and muscle mass, an increase in MHC (myosin heavy chain)
      degradation, and an increase in the expression of atrogin-1 and MuRF-1 (muscle
      specific RING-finger protein 1), two ubiquitin E3 ligases belonging to the
      ubiquitin-proteasome system. Ang-(1-7) [Angiotensin-(1-7)], through its Mas
      receptor, has beneficial effects in skeletal muscle. We evaluated in vivo the
      role of Ang-(1-7) and Mas receptor on the muscle wasting induced by LPS injection
      into C57BL/10J mice. In vitro studies were performed in murine C2C12 myotubes and
      isolated myofibres from EDL (extensor digitorum longus) muscle. In addition, the
      participation of p38 MAPK (mitogen-activated protein kinase) in the Ang-(1-7)
      effect on the LPS-induced muscle atrophy was evaluated. Our results show that Ang
      (1-7) prevents the decrease in the diameter of myofibres and myotubes, the
      decrease in muscle strength, the diminution in MHC levels and the induction of
      atrogin-1 and MuRF-1 expression, all of which are induced by LPS. These effects
      were reversed by using A779, a Mas antagonist. Ang-(1-7) exerts these anti
      atrophic effects at least in part by inhibiting the LPS-dependent activation of
      p38 MAPK both in vitro and in vivo. We have demonstrated for the first time that
      Ang-(1-7) counteracts the skeletal muscle atrophy induced by endotoxin through a
      mechanism dependent on the Mas receptor that involves a decrease in p38 MAPK
      phosphorylation. The present study indicates that Ang-(1-7) is a novel molecule
      with a potential therapeutic use to improve muscle wasting during endotoxin
      induced sepsis syndrome.

PMID- 25989284
TI  - Pharmacokinetics of Ferrous Sulphate (Tardyferon(r)) after Single Oral Dose
      Administration in Women with Iron Deficiency Anaemia.
AB  - Iron-containing preparations available on the market vary in dosage, salt, and
      chemical state of iron contained in the preparation, as well as in the iron
      delivery process (immediate or prolonged-release). The present study aimed at
      characterizing the serum pharmacokinetics of iron in non pregnant women with iron
      deficiency anaemia (IDA) following a single oral administration of a prolonged
      release ferrous sulphate tablet. This multicenter, single dose, open-label study
      was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg
      oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon((r))
      under fasting conditions. Blood samples were collected before dosing and until 24
      h post-dosing. Serum iron concentrations were determined using a routine
      colorimetric analytical method. Pharmacokinetic parameters were determined from
      the serum concentration profiles using a non compartmental approach. Serum
      profiles showed elevated levels of iron up to 12 h after drug intake. The median
      time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2
      and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%.
      Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax,
      respectively. This study demonstrates that a single oral dose of 160 mg
      Tardyferon((r)) administered under fasting condition to 30 women with IDA leads
      to an optimal long-lasting release of iron in the gastrointestinal tract in the
      targeted population. This allows the attainment and maintenance of elevated serum
      iron levels for up to 12 h after administration.

PMID- 25989285
TI  - Microscopic Image Photography Techniques of the Past, Present, and Future.
AB  - CONTEXT: The field of pathology is driven by microscopic images. Educational
      activities for trainees and practicing pathologists alike are conducted through
      exposure to images of a variety of pathologic entities in textbooks,
      publications, online tutorials, national and international conferences, and
      interdepartmental conferences. During the past century and a half, photographic
      technology has progressed from primitive and bulky, glass-lantern projector
      slides to static and/or whole slide digital-image formats that can now be
      transferred around the world in a matter of moments via the Internet. OBJECTIVE:
      To provide a historic and technologic overview of the evolution of microscopic
      image photographic tools and techniques. DATA SOURCES: Primary historic methods
      of microscopic image capture were delineated through interviews conducted with
      senior staff members in the Emory University Department of Pathology. Searches
      for the historic image-capturing methods were conducted using the Google search
      engine. Google Scholar and PubMed databases were used to research methods of
      digital photography, whole slide scanning, and smart phone cameras for
      microscopic image capture in a pathology practice setting. CONCLUSIONS: Although
      film-based cameras dominated for much of the time, the rise of digital cameras
      outside of pathology generated a shift toward digital-image capturing methods,
      including mounted digital cameras and whole slide digital-slide scanning. Digital
      image capture techniques have ushered in new applications for slide sharing and
      second-opinion consultations of unusual or difficult cases in pathology. With
      their recent surge in popularity, we suspect that smart phone cameras are poised
      to become a widespread, cost-effective method for pathology image acquisition.

PMID- 25989286
TI  - Keratin Expression Patterns in Stromal Cells of Benign Sclerosing Lesions of the
      Breast: A Potential Diagnostic Pitfall.
AB  - CONTEXT: Metaplastic carcinomas arising in association with benign sclerosing
      lesions (BSLs) are rare malignancies in which a neoplastic spindle cell
      proliferation can be recognized extending beyond the boundaries of the complex
      sclerosing lesion or papilloma. However, in cases in which the metaplastic
      carcinoma is of the low-grade fibromatosis-like type or is a low-grade
      adenosquamous carcinoma, distinction from the background BSL can be a significant
      challenge. Cytokeratin (CK) and/or p63 immunostains are helpful in confirming the
      diagnosis of metaplastic carcinoma, but the expression patterns of these markers
      in the stromal cells of BSLs have not been well characterized. OBJECTIVE: To
      characterize the expression patterns of CKs and p63 in BSLs. DESIGN: We evaluated
      the spindle cell component of 55 BSLs using CK 5/6, CK 903, CK MNF116, and p63.
      RESULTS: A total of 45 cases (81%) showed no staining for CKs or p63 in benign
      stromal cells. CK 5/6, CK 903, and p63 were positive in one case each. CK MNF116
      stained spindle cells within 10 BSLs. No cases showed spindle cell reactivity for
      all 4 markers. Positive cases demonstrated very focal, weak staining of spindle
      cells; only 1 case showed focal, moderate CK staining. Spindle cell positivity
      was not associated with lesion type, growth pattern, spindle cell atypia, or
      mitoses. CONCLUSIONS: These findings suggest that although the presence or
      absence of expression of CK 5/6, CK 903, and p63 may be useful to distinguish BSL
      from metaplastic carcinomas arising in this setting, CK MNF116 positivity may be
      a diagnostic pitfall.

PMID- 25989288
TI  - Gonadotropins and Growth Hormone Family Characterization in an Endangered
      Siluriform Species, Steindachneridion parahybae (Pimelodidae): Relationship With
      Annual Reproductive Cycle and Induced Spawning in Captivity.
AB  - The aim of this study was to identify and characterize pituitary cells of
      Steindachneridion parahybae females in captivity, highlighting the possible
      relationship with reproductive disorders at this level, since this species shows
      oocyte final maturation, ovulation and spawning dysfunction in captivity. The
      localization and distribution of growth hormone (GH), prolactin (PRL),
      somatolactin (SL), beta-luteinizing hormone (beta-LH), and beta-follicle
      stimulating hormone (beta-FSH) immunoreactive (-ir) cells in the adenohypophysis
      was studied by immunohistochemical and Western blot methods. In addition,
      cellular morphometric analyses and semi-quantification of ir-cells optical
      density (OD) during the annual reproductive cycle and after artificial induced
      spawning (AIS) were performed. Results showed that the distribution and general
      localization of pituitary cell types were similar to that of other teleost
      species. However, the morphometrical study of adenohypophysial cells showed
      differences along the reproductive cycle and following AIS. In general, females
      at the vitellogenic stage presented greater OD values for GH, PRL and SL than at
      other maturation stages (previtellogenic and regression stages), probably
      indicating an increased cellular activity during this stage. Conversely, beta-LH
      OD did not vary during the annual reproductive cycle. After AIS, beta-LH, SL and
      GH ir-cells showed an increase in OD values suggesting a possible involvement on
      oocyte final maturation, ovulation and spawning or a feedback control on the
      brain-pituitary-gonads axis. Reproductive dysfunction in S. parahybae females in
      captivity may be due to alteration of the synthesis pathways of beta-LH. In
      addition, GH family of hormones could modulate associated mechanisms that
      influence the reproductive status in this species.

PMID- 25989287
TI  - The World Health Organization Classification of Skeletal Muscle Tumors in
      Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group.
AB  - CONTEXT: The World Health Organization Classification Since 1995, the
      International Classification of Rhabdomyosarcoma has provided prognostically
      relevant classification for rhabdomyosarcoma (RMS) and allowed risk
      stratification for children with RMS. The International Classification of
      Rhabdomyosarcoma includes botryoid and spindle cell RMS as superior-risk groups,
      embryonal RMS as an intermediate-risk group, and alveolar RMS as an unfavorable
      risk group. The 2013 World Health Organization (WHO) classification of skeletal
      muscle tumors modified the histologic classification of RMS to include sclerosing
      RMS as a type of spindle cell RMS separate from embryonal RMS. The current WHO
      classification includes embryonal, alveolar, spindle cell/sclerosing, and
      pleomorphic subtypes of RMS and does not separate the botryoid subtype.
      OBJECTIVE: To determine if the WHO classification applies to pediatric RMS.
      DESIGN: To accomplish this goal, we reviewed 9 consecutive Children's Oncology
      Group clinical trials to compare the WHO and International Classification of
      Rhabdomyosarcoma classifications with outcome and site of disease. RESULTS:
      Except for a subset of low-risk RMS, the outcome for botryoid was not
      significantly different from typical embryonal RMS when analyzed by primary site.
      Similarly, pediatric spindle cell and sclerosing patterns of RMS did not appear
      significantly different from typical embryonal RMS, with one exception: spindle
      cell RMS in the parameningeal region had an inferior outcome with 28% event-free
      survival. CONCLUSION: Our data support use of the WHO RMS classification in the
      pediatric population, with the caveat that histologic diagnosis does not
      necessarily confer the same prognostic information in children as in adults.

PMID- 25989289
TI  - Epidemiological and genetic analysis concerning the coxsackievirus A6 related
      endemic outbreak of hand-foot-mouth disease in Taizhou, China, during 2013.
AB  - A total of 1,098 strains of human enteroviruses (HEV), falling into 14 serotypes
      were detected upon analysis of 1,509 hand-foot-mouth disease (HFMD) samples
      collected in Taizhou during the period from July 2010 to December 2013. And a CV
      A6 related HFMD outbreak was identified in Taizhou during 2013. Phylogenic
      analyses of complete VP1 sequences indicate that this outbreak of HFMD in Taizhou
      is closely related to the global outbreaks of CV-A6 related HFMD since 2008, but
      the analyses also indicate that the outbreak in Taizhou is rather an endemic
      outbreak in which a phylogenic sub-group of CV-A6 was identified whose members
      commonly acquired a mutation R->K at site 254 of VP1 protein. It is interesting
      that the emergence of the sub-group was inferred to contribute to the endemic
      outbreak in Taizhou in 2013.

PMID- 25989291
TI  - Intrathecal Therapy: The Burden of Being Positioned as a Salvage Therapy.

PMID- 25989292
TI  - Pharmacokinetics and bioequivalence testing of five commercial formulations of
      omeprazole in the horse.
AB  - Omeprazole is widely used in the treatment of equine gastric ulcer syndrome. To
      date, little is known about the relative pharmacokinetics of the different
      formulations making comparisons between products difficult. The objectives of the
      study were to investigate the relative pharmacokinetics of five commercially
      available formulations of omeprazole in the horse and to test for bioequivalence
      of four of the formulations using one of the formulations as a reference
      standard. Twelve mature Thoroughbred horses were fasted for 16 h then
      administered 2 g of each formulation in a cross-over design. Serial blood samples
      were collected and plasma omeprazole concentration was determined by ultra high
      performance liquid chromatography-mass spectrometry (UHPLC-MS). No significant
      differences were present between three of the formulations and the reference
      formulation, while the fourth formulation had a lower Cmax and longer Tmax than
      the reference formulation. Bioequivalence against the reference formulation could
      not be demonstrated for any of the formulations tested. The findings of the study
      suggested that the method of protection utilised by different formulations of
      omeprazole (enteric-coated granules vs. buffering) does not significantly alter
      the pharmacokinetics of the drug. Further work to establish bioequivalence is
      needed before direct comparisons can be drawn between different formulations.

PMID- 25989290
TI  - The GPR 55 agonist, L-alpha-lysophosphatidylinositol, mediates ovarian carcinoma
      cell-induced angiogenesis.
AB  - BACKGROUND AND PURPOSE: Highly vascularized ovarian carcinoma secretes the
      putative endocannabinoid and GPR55 agonist, L-alpha-lysophosphatidylinositol
      (LPI), into the circulation. We aimed to assess the involvement of this agonist
      and its receptor in ovarian cancer angiogenesis. EXPERIMENTAL APPROACH: Secretion
      of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was
      tested by mass spectrometry. Involvement of cancer cell-derived LPI on
      angiogenesis was tested in the in vivo chicken chorioallantoic membrane (CAM)
      assay along with the assessment of the effect of LPI on proliferation, network
      formation, and migration of neonatal and adult human endothelial colony-forming
      cells (ECFCs). Engagement of GPR55 was verified by using its pharmacological
      inhibitor CID16020046 and diminution of GPR55 expression by four different target
      specific siRNAs. To study underlying signal transduction, Western blot analysis
      was performed. KEY RESULTS: Ovarian carcinoma cell-derived LPI stimulated
      angiogenesis in the CAM assay. Applied LPI stimulated proliferation, network
      formation, and migration of neonatal ECFCs in vitro and angiogenesis in the in
      vivo CAM. The pharmacological GPR55 inhibitor CID16020046 inhibited LPI
      stimulated ECFC proliferation, network formation and migration in vitro as well
      as ovarian carcinoma cell- and LPI-induced angiogenesis in vivo. Four target
      specific siRNAs against GPR55 prevented these effects of LPI on angiogenesis.
      These pro-angiogenic effects of LPI were transduced by GPR55-dependent
      phosphorylation of ERK1/2 and p38 kinase. CONCLUSIONS AND IMPLICATIONS: We
      conclude that inhibiting the pro-angiogenic LPI/GPR55 pathway appears a promising
      target against angiogenesis in ovarian carcinoma.

PMID- 25989293
TI  - Gathering Storm Clouds Suggest the Need for a Culture Change in Radiology:
      Radiologist-centered Imaging.

PMID- 25989294
TI  - Improving Network Structure can lead to Functional Failures.
AB  - In many real-world networks the ability to synchronize is a key property for
      their performance. Recent work on undirected networks with diffusive interaction
      revealed that improvements in the network connectivity such as making the network
      more connected and homogeneous enhances synchronization. However, real-world
      networks have directed and weighted connections. In such directed networks,
      understanding the impact of structural changes on the network performance remains
      a major challenge. Here, we show that improving the structure of a directed
      network can lead to a failure in the network function. For instance, introducing
      new links to reduce the minimum distance between nodes can lead to instabilities
      in the synchronized motion. This effect only occurs in directed networks. Our
      results allow to identify the dynamical importance of a link and thereby have a
      major impact on the design and control of directed networks. 

PMID- 25989295
TI  - The role of emotions in time to presentation for symptoms suggestive of cancer: a
      systematic literature review of quantitative studies.
AB  - BACKGROUND: Emotions may be important in patients' decisions to seek medical help
      for symptoms suggestive of cancer. OBJECTIVES: The aim of this systematic
      literature review was to examine quantitative literature on the influence of
      emotion on patients' help-seeking for symptoms suggestive of cancer. The
      objectives were to identify the following: (a) which types of emotions influence
      help-seeking behaviour, (b) whether these form a barrier or trigger for seeking
      medical help and (c) how the role of emotions varies between different cancers
      and populations. METHODS: We searched four electronic databases and conducted a
      narrative synthesis. Inclusion criteria were studies that reported primary,
      quantitative research that examined any emotion specific to symptom appraisal or
      help-seeking for symptoms suggestive of cancer. RESULTS: Thirty-three papers were
      included. The studies were heterogeneous in their methods and quality, and very
      few had emotion as the main focus of the research. Studies reported a limited
      range of emotions, mainly related to fear and worry. The impact of emotions
      appears mixed, sometimes acting as a barrier to consultation whilst at other
      times being a trigger or being unrelated to time to presentation. It is plausible
      that different emotions play different roles at different times prior to
      presentation. CONCLUSIONS: This systematic review provides some quantitative
      evidence for the role of emotions in help-seeking behaviour. However, it also
      highlighted widespread methodological, definition and design issues among the
      existing literature. The conflicting results around the role of emotions on time
      to presentation may be due to the lack of definition of each specific emotion.

PMID- 25989296
TI  - Kaposi's sarcoma simulating verrucous syndrome.

PMID- 25989297
TI  - Poly Implant Prothese: Two Studies of the Same Topic.

PMID- 25989298
TI  - Remote Ischemic Preconditioning Improves the Viability of Donor Lipoaspirate
      during Murine Fat Transfer.
AB  - BACKGROUND: Variable results associated with fat grafting have been attributed to
      local trauma, inconsistencies in transfer, and ischemia before the development of
      recipient circulation. Remote ischemic preconditioning is an inexpensive
      noninvasive technique that has been used in animal models and multicenter
      clinical trials to protect organ systems. In this work, the authors describe a
      novel animal model for analyzing the efficacy of fat grafting, and investigate
      the effect of remote ischemic preconditioning on volume retention. METHODS:
      Subcutaneous adipose tissue samples from green fluorescent protein/luciferase
      expressing FVB mice were obtained with or without pretreatment with a temporary
      hind-limb tourniquet. The samples were injected into the dorsal skin folds of
      wild-type FVB mice. The viability of the transferred tissue was examined over a
      28-day period with quantitative bioluminescence after luciferin injection.
      Transferred tissue was also explanted for histologic analysis. RESULTS: The
      remote ischemic preconditioning group had significantly increased bioluminescence
      at days 0, 1, and 28. Histologic analysis at day 28 confirmed the presence of
      vascularized adipose in both groups. However, significant amounts of interstitial
      fibrosis were found in the control group, whereas substantially less was found in
      the remote ischemic preconditioning group. The remote ischemic preconditioning
      group retained a substantially greater amount of green fluorescent protein,
      suggesting increased survival of donor adipocytes. CONCLUSIONS: In this work, the
      authors describe a novel animal model for quantitative evaluation of fat grafting
      using in vivo bioluminescence of adipocytes from luciferase-expressing mice. The
      authors also demonstrate that remote ischemic preconditioning increases the
      viability of fat transfer and decreases interstitial fibrosis.

PMID- 25989299
TI  - Face Lifting in the Massive Weight Loss Patient: Modifications of Our Technique
      for This Population.

PMID- 25989301
TI  - Comparison of Traditional versus Normative Cephalic Index in Patients with
      Sagittal Synostosis: Measure of Scaphocephaly and Postoperative Outcome.
AB  - BACKGROUND: Preoperative severity and postoperative success for patients with
      sagittal synostosis are measured by cephalic index, but this metric does not
      describe the appropriateness of euryon location. The authors hypothesize that
      cephalic index in patients with sagittal synostosis is an inaccurate measure of
      scaphocephaly. METHODS: Preoperative and 1-year postoperative cranial computed
      tomographic scans of children with sagittal synostosis treated before 6 months of
      age by either total calvarial reconstruction or endoscope-assisted craniectomy
      and helmet therapy (n = 10 for each) were reviewed retrospectively. The location
      of euryons in age-matched controls was measured as a fraction of the glabella
      opisthocranion distance (horizontal point of maximum width) and as the fraction
      of the nasion-vertex vertical distance (vertical point of maximum width).
      Cephalic index at this ideal location (normative cephalic index) and traditional
      cephalic index were determined in all patients. RESULTS: Ideal euryon location
      from preoperative controls was 56 percent by the horizontal point of maximum
      width and 56 percent by the vertical point of maximum width. Normative cephalic
      index (0.60) was significantly less than traditional cephalic index (0.66) in
      patients preoperatively (p < 0.001) and remained smaller postoperatively (0.68
      versus 0.73) for patients who underwent open reconstruction (p < 0.001). Patients
      treated endoscopically also had a smaller normative cephalic index (0.71) than
      traditional cephalic index (0.76) postoperatively (p < 0.001). CONCLUSIONS:
      Anterocaudal displacement of euryon in patients with sagittal synostosis
      influences cephalic index. Normative cephalic index, assessed at ideal euryon
      location, is a more accurate measure of preoperative severity and postoperative
      outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, III.

PMID- 25989300
TI  - Burn Scar Biomechanics after Pressure Garment Therapy.
AB  - BACKGROUND: The current standard of care for the prevention and treatment of
      scarring after burn injury is pressure garment therapy. Although this therapy has
      been used clinically for many years, controversy remains regarding its efficacy.
      The authors evaluated the efficacy of pressure garment therapy in a female red
      Duroc pig burn model in which wound depth could be tightly controlled. METHODS:
      Full-thickness burn wounds were generated on female red Duroc pigs. At day 28
      after burn, pressure garment therapy was applied to half the wounds (10 mmHg),
      with control wounds covered with garments that exerted no compression. Scar area,
      perfusion, hardness, and elasticity were quantified at days 0, 28, 42, 56, and 72
      using computerized planimetry, laser Doppler, and torsional ballistometry. Scar
      morphology was assessed at days 28, 56, and 76 using histology,
      immunohistochemistry, and transmission electron microscopy. RESULTS: Pressure
      garment therapy significantly hindered scar contraction, with control scars
      contracting to 64.6 percent + 13.9 percent original area at day 72, whereas
      pressure garment therapy scars contracted to 82.7 percent + 17.9 percent original
      area. Pressure garments significantly reduced skin hardness and increased skin
      strength by 1.3 times. No difference in perfusion or blood vessel density was
      observed. The average collagen fiber diameter was greater in control burns than
      in pressure garment therapy. CONCLUSIONS: Pressure garment therapy was effective
      at reducing scar contraction and improving biomechanics compared with control
      scars. These results confirm the efficacy of pressure garments and highlight the
      need to further investigate the role of pressure magnitude and the time of
      therapy application to enhance efficacy for optimal biomechanics and patient
      mobility.

PMID- 25989302
TI  - Submandibular Gland Reduction in Aesthetic Surgery of the Neck: Review of 112
      Consecutive Cases.
AB  - BACKGROUND: The indications for reduction of excessive submandibular gland volume
      in aesthetic rejuvenation of the neck have been well described, as has the
      surgical anatomy and the surgical technique. Despite this, submandibular gland
      reduction does not appear to be widely adopted, nor have significant case series
      been reported in the literature. This review of a consecutive series of aesthetic
      submandibular gland reductions was undertaken to provide a perspective about its
      place in neck contouring. METHODS: A retrospective chart review was conducted of
      all patients on whom the senior author (B.C.M.) had performed submandibular gland
      reduction for aesthetic reasons. Complications and reoperations were specifically
      analyzed. RESULTS: Submandibular gland reduction was performed in 112 of 736
      consecutive face lifts between 2002 and 2013, an incidence of 13 percent in
      primary face lifts and 25 percent in secondary face lifts. The median patient age
      was 57 years, and 87 percent were women. Major complications were those requiring
      early reoperation (1.8 percent) to manage significant hematomas; one was
      potentially fatal. Minor complications (10.8 percent) were managed
      nonoperatively. Submandibular sialocele (4.5 percent) and marginal mandibular
      branch neurapraxia (4.5 percent) were the most frequent, and all resolved fully
      by 3 months. Significantly, no patient reported a permanent dry mouth.
      CONCLUSIONS: The complication rate with submandibular gland reduction is
      comparable to that of a neck lift with platysma plication alone, with some
      additional specific risks: (1) catastrophic airway compression from bleeding deep
      in the neck, (2) significant increase of neurapraxias in secondary neck lifts,
      and (3) a moderate incidence of benign submandibular sialocele. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25989303
TI  - Defining the Role of Skin and Mucosal Biopsy in Facial Allotransplantation: A 2
      Year Review and Analysis of Histology.
AB  - BACKGROUND: The implications of allograft skin and mucosal biopsy findings on
      classification of rejection and treatment remain unclear. METHODS: Following
      facial allotransplantation, scheduled surveillance allograft skin and mucosal
      biopsy specimens were obtained. Clinical concern for acute rejection prompted
      biopsies off schedule. Compilation of biopsy results, Banff grading,
      immunosuppression, and clinical correlation were critically reviewed for a 2-year
      follow-up. RESULTS: A total of 39 biopsy specimens at 21 time points were
      obtained for analysis, including allograft skin (n = 21), mucosa (n = 17), and a
      lesion (n = 1). The patient had three episodes of acute rejection warranting
      treatment. Discordance between skin and mucosa occurred in 55.6 percent of biopsy
      specimens (p = 0.01). Mucosa concordance with the clinical evaluation occurred in
      38.9 percent of biopsy specimens (p = 0.02), and skin concordance with clinical
      evaluation was present in 81 percent of biopsy specimens (p = 0.01). CONCLUSIONS:
      The clinical utility of mucosal biopsy remains elusive. The authors' experience
      suggests that mucosal or skin biopsy, alone, should not drive the decision-making
      process in treatment. Skin biopsies are more likely to confirm clinical suspicion
      of rejection than mucosal histology. Data from other institutions are lacking,
      and future reporting may help elucidate the role of mucosal and skin biopsy in
      facial allotransplantation. CLINICAL QUESTIONS/LEVEL OF EVIDENCE: Diagnostic, V.

PMID- 25989304
TI  - Skin Grafts for Residual Limb Coverage and Preservation of Amputation Length.
AB  - BACKGROUND: Split-thickness skin grafts have historically been used sparingly for
      amputation coverage when delayed primary closure is not feasible without
      substantial loss of length. The authors investigated the use of split-thickness
      skin grafts in the residual limbs of combat-related amputees. METHODS: A
      retrospective review was completed on consecutive amputations of 300 lower and
      100 upper extremities treated at Walter Reed National Military Medical Center
      from 2003 to 2009, comparing patients treated with split-thickness skin grafts
      with those treated with delayed primary closure. Principal outcomes measured
      included early (wound failure) and late (heterotopic ossification requiring
      excision and soft-tissue revisions) complications requiring surgery. RESULTS:
      Statically significant differences were seen, with the split-thickness skin graft
      group having an increased incidence of wound failure (p < 0.022), heterotopic
      ossification requiring excision (p < 0.001), and soft-tissue revisions (p <
      0.001) compared with controls. The risk of revision was higher for lower
      extremity than for upper extremity amputations undergoing skin grafting. However,
      amputation level salvage, maintaining the proximal joint, was successful for all
      residual limbs with split-thickness skin grafts. CONCLUSIONS: Split-thickness
      skin grafts for closure of amputations result in significantly increased
      reoperation rates, but they are ultimately successful in salvaging residual limb
      length and amputation levels. In carefully selected patients, they may be a
      successful means of achieving definitive coverage when performed over robust,
      healthy muscle. In many patients, however, they should be viewed as a staging
      procedure to maintain length and amputation level until swelling decreases and
      revision surgery for split-thickness skin graft excision with or without
      concurrent procedures can be performed without the need to substantially shorten
      the residual limb.

PMID- 25989305
TI  - Surgical Technique and Clinical Results for Trapeziometacarpal Arthrodesis Using
      Locking Plate Fixation in Women Aged 50 Years or Older.
AB  - BACKGROUND: The authors hypothesized that locking plates have the potential to
      decrease the risk of nonunion for trapeziometacarpal joint arthrodesis and
      eliminate the period of postoperative immobilization. The surgical technique is
      described and the clinical results are reported for Eaton stage III
      trapeziometacarpal joint arthrodesis using locking plate fixation in elderly
      women. METHODS: The outcomes of 18 fusion operations with a 2-year follow-up were
      assessed during this prospective study. Patients were evaluated for bone union,
      grip strength, tip and key pinch strength, and Kapandji opposition scores. The
      Disabilities of the Arm, Shoulder and Hand questionnaire and visual analogue
      scale pain scores were obtained from the patients and evaluated. In addition,
      complications were assessed. RESULTS: Bone unions were obtained for 16 of 18
      fusions. Grip strength was 18.3 kg (range, 12.5 to 26.0 kg), tip pinch strength
      was 5.6 kg (range, 3.5 to 7.5 kg), and key pinch strength was 6.4 kg (range, 4.0
      to 7.5 kg). The Kapandji opposition score was 8.3 points (range, 8 to 10).
      Disabilities of the Arm, Shoulder and Hand questionnaire score decreased from
      54.2 (range, 68.8 to 39.4) to 8.8 (range, 3.9 to 22.0), and visual analogue scale
      pain scores decreased from 8.3 (range, 8 to 10) preoperatively to 0.9 (range, 0
      to 4) postoperatively. Malpositioned devices were removed from two patients. One
      symptomatic patient required removal of the fixation device as a result of
      hardware loosening. CONCLUSION: The results for arthrodesis with a locking plate
      are comparable to results with a nonlocking plate and are quite satisfactory in
      the appropriate hands. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25989307
TI  - Intralesional Cryotherapy for Treatment of Keloid Scars: A Prospective Study.

PMID- 25989308
TI  - Reply: Intralesional Cryotherapy for the Treatment of Keloid Scars: A Prospective
      Study.

PMID- 25989309
TI  - Reply: Practical Guidelines for Venous Thromboembolism Chemoprophylaxis in
      Elective Plastic Surgery.

PMID- 25989310
TI  - The Limitations of Chemoprophylaxis and Advantages of Alternative Methods to
      Reduce the Risk of Thromboembolism.

PMID- 25989311
TI  - Special focus issue on the annual meeting of the British Society for Gene and
      Cell Therapy.

PMID- 25989312
TI  - Dialkyl phosphates determination by gas chromatography: Evaluation of a microwave
      assisted derivatization?.
AB  - Dialkyl phosphates are organophosphate insecticide metabolites and their urinary
      analysis is useful for assessing human exposure to these compounds. This study
      presents a sample preparation method with microwave-assisted derivatization for
      two dialkyl phosphates to make the process faster before gas chromatographic
      analysis. The optimized conditions for derivatization procedure were: 250 MUL of
      2,3,4,5,6-pentafluorobenzyl bromide 3% in acetonitrile for derivative; microwave
      for 5 min with intensity of 160 W. The electron ionization mass spectrometric
      analysis was performed using a gas chromatography with mass spectrometry QP-2010
      from the Shimadzu((r)) equipped with RTx((r)) -5MS capillary column. Ions were
      monitored at selected-ion monitoring mode at m/z 350 for diethyl thiophosphate
      and m/z 366 for diethyl dithiophosphate. The developed method was linear for both
      metabolites. The intra-assay precision was the values ranged between 1.1 and
      9.1%, for diethyl thiophosphate, and between 4.06 and 6.9%, for diethyl
      dithiophosphate. The interassay precision showed relative standard deviation
      between 10.3 and 15.1%, for diethyl thiophosphate and between 4.9 and 11.9%, for
      diethyl dithiophosphate. The results obtained suggests that derivatization
      assisted by microwave, before gas chromatography with mass spectrometry analysis,
      can be applied to monitoring of exposure to organophosphates once is fast,
      sensible, and precise method to determinate dialkyl phosphates. 

PMID- 25989313
TI  - Super-long life time for 2D cyclotron spin-flip excitons.
AB  - An experimental technique for the indirect manipulation and detection of electron
      spins entangled in two-dimensional magnetoexcitons has been developed. The
      kinetics of the spin relaxation has been investigated. Photoexcited spin
      magnetoexcitons were found to exhibit extremely slow relaxation in specific
      quantum Hall systems, fabricated in high mobility GaAs/AlGaAs structures; namely,
      the relaxation time reaches values over one hundred microseconds. A qualitative
      explanation of this spin-relaxation kinetics is presented. Its temperature and
      magnetic field dependencies are discussed within the available theoretical
      framework. 

PMID- 25989314
TI  - Influence of the propagation strategy for obtaining robust Saccharomyces
      cerevisiae cells that efficiently co-ferment xylose and glucose in
      lignocellulosic hydrolysates.
AB  - Development of xylose-fermenting yeast strains that are tolerant to the
      inhibitors present in lignocellulosic hydrolysates is crucial to achieve
      efficient bioethanol production processes. In this study, the importance of the
      propagation strategy for obtaining robust cells was studied. Addition of
      hydrolysate during propagation of the cells adapted them to the inhibitors,
      resulting in more tolerant cells with shorter lag phases and higher specific
      growth rates in minimal medium containing acetic acid and vanillin than unadapted
      cells. Addition of hydrolysate during propagation also resulted in cells with
      better fermentation capabilities. Cells propagated without hydrolysate were
      unable to consume xylose in wheat straw hydrolysate fermentations, whereas 40.3%
      and 97.7% of the xylose was consumed when 12% and 23% (v/v) hydrolysate,
      respectively, was added during propagation. Quantitative polymerase chain
      reaction revealed changes in gene expression, depending on the concentration of
      hydrolysate added during propagation. This study highlights the importance of
      using an appropriate propagation strategy for the optimum performance of yeast in
      fermentation of lignocellulosic hydrolysates. 

PMID- 25989315
TI  - Human NCL Neuropathology.
AB  - The neuronal ceroid lipofuscinoses (NCL) currently encompass fourteen genetically
      different forms, CLN1 to CLN14, but are all morphologically marked by loss of
      nerve cells, particularly in the cerebral and cerebellar cortices, and the
      cerebral and extracerebral formation of lipopigments. These lipopigments show
      distinct ultrastructural patterns, i.e., granular, curvilinear/rectilinear and
      fingerprint profiles. They contain-although to a different degree among the
      different CLN forms-subunit C of ATP synthase, saposins A and D, and beta-amyloid
      proteins. Extracerebral pathology, apart from lipopigment formation, which
      provides diagnostic information, is scant or non-existent. The retina undergoes
      atrophy in all childhood forms. While many new data and findings have been
      obtained by immunohistochemistry in mouse and other animal models, similar
      findings in human NCL are largely missing, thus recommending respective studies
      of archived brain tissues. The newly described NCL forms, i.e., CLN 10 to CLN 14,
      also require further studies to provide complete neuropathology. This article is
      part of a Special Issue entitled: "Current Research on the Neuronal Ceroid
      Lipofuscinoses (Batten Disease)". 

PMID- 25989316
TI  - Children with Williams syndrome: Developmental trajectories for intellectual
      abilities, vocabulary abilities, and adaptive behavior.
AB  - To examine longitudinal trajectories of intellectual abilities, single-word
      vocabulary abilities, and adaptive behavior for 76 children with Williams
      syndrome (WS) aged 4-15 years, we compared their standard scores (SSs) at two
      time points approximately 3 years apart on the same standardized measures. At the
      group level, mean SS declined significantly for 8 of the 12 measures and showed a
      slight (nonsignificant) increase or decrease for 4 measures. However, for most
      measures significant changes in SS were found for only a small proportion of the
      children, with some children evidencing significant declines and a smaller
      proportion evidencing significant increases. Significant SS changes were most
      common for adaptive behavior. For all measures, the mean magnitude of SS change
      was smaller for older children (>7.5 years at Time 1) than for younger children
      (<7.5 years at Time 1). Furthermore, correlations between Time 1 and Time 2 SSs
      were larger for the older cohort than for the younger cohort, indicating that SS
      stability was greater for older children than for younger children. Although mean
      SSs declined for most measures, indicating that children with WS as a group were
      not making the expected amount of progress relative to their general population
      peers who earned the same SS at Time 1, there was little evidence either of
      regression (loss of skills) or stagnation (failure to increase raw scores). The
      relations of these results to those of previous smaller-sample longitudinal
      studies of children with WS and the implications of the findings are considered.

PMID- 25989317
TI  - An fMRI investigation into the effect of preceding stimuli during visual oddball
      tasks.
AB  - BACKGROUND: This study investigates the modulatory effect of stimulus sequence on
      neural responses to novel stimuli. A group of 34 healthy volunteers underwent
      event-related functional magnetic resonance imaging while performing a three
      stimulus visual oddball task, involving randomly presented frequent stimuli and
      two types of infrequent stimuli - targets and distractors. NEW METHOD: We
      developed a modified categorization of rare stimuli that incorporated the type of
      preceding rare stimulus, and analyzed the event-related functional data according
      to this sequence categorization; specifically, we explored hemodynamic response
      modulation associated with increasing rare-to-rare stimulus interval. RESULTS:
      For two consecutive targets, a modulation of brain function was evident
      throughout posterior midline and lateral temporal cortex, while responses to
      targets preceded by distractors were modulated in a widely distributed fronto
      parietal system. As for distractors that follow targets, brain function was
      modulated throughout a set of posterior brain structures. For two successive
      distractors, however, no significant modulation was observed, which is consistent
      with previous studies and our primary hypothesis. COMPARISON WITH EXISTING
      METHODS: The addition of the aforementioned technique extends the possibilities
      of conventional oddball task analysis, enabling researchers to explore the
      effects of the whole range of rare stimuli intervals. CONCLUSION: This
      methodology can be applied to study a wide range of associated cognitive
      mechanisms, such as decision making, expectancy and attention.

PMID- 25989318
TI  - Sin and pleasure: the history of chocolate in medicine.
AB  - In ancient Mayan texts cocoa is considered a gift of the gods: Pre-Columbian
      populations used chocolate as medicine, too. After the discovery of America,
      chocolate was introduced in Europe, but Christian Europe looked to this new
      exhilarating drink with extreme suspiciousness and criticism. From this reaction,
      the necessity derived to appeal to the reasons of health, with which doctors and
      scientists committed themselves to explain that chocolate was good for the body.
      However, during the Enlightment, the road of therapy separated from that of
      taste, and chocolate mainly maintained its leading role of excipient, bearing the
      burden, over time, of a negative valence, being associated with obesity, dental
      problems, unhealthy lifestyle, and so forth. The rehabilitation of chocolate has
      arisen only in recent times, re-establishing that value that Linnaeus himself
      credited to chocolate, calling the generous plant Theobroma cacao, food of the
      gods. 

PMID- 25989319
TI  - Community-Level Quality Improvement and the Patient Experience for Chronic
      Illness Care.
AB  - OBJECTIVE: To determine whether chronically ill adults from communities
      participating in a community-level quality improvement effort reported greater
      improvement on four domains of patient experience: care coordination, patient
      satisfaction, provider interaction and support, and receipt of recommended care
      for diabetes. STUDY SETTING: The Robert Wood Johnson Foundation's Aligning Forces
      for Quality (AF4Q) initiative provides multistakeholder alliances with funding
      and technical assistance to improve quality in their communities. STUDY DESIGN:
      This is a quasi-experimental, pre-post study. We used a difference-in-difference
      approach to detect relative changes over time on 16 survey-based outcome measures
      representing the four patient experience domains. DATA COLLECTION: We surveyed
      adults with chronic illness(es) in 14 AF4Q communities and a national comparison
      group. Wave 1 was completed in 2008 (8,140 respondents) and wave 2 in 2012 (9,565
      respondents). PRINCIPAL FINDINGS: Respondents from AF4Q communities reported
      modestly greater improvement on patient satisfaction and receipt of recommended
      care for diabetes. CONCLUSIONS: Results suggest that community-level QI efforts
      led by multistakeholder alliances hold the potential to improve patient
      satisfaction and receipt of recommended care for diabetes, but the magnitude of
      the effect may be limited. However, there is less evidence that community-level
      QI can improve patient perceptions of care coordination or provider interaction
      and support.

PMID- 25989320
TI  - Extensively drug-resistant New Delhi metallo-beta-lactamase-encoding bacteria in
      the environment, Dhaka, Bangladesh, 2012.
AB  - Carriage of the New Delhi metallo-beta-lactamase variant 1 (NDM-1) enables drug
      resistance to move between communities and hospitals. In Bangladesh, we found the
      blaNDM-1 gene in 62% of environmental waters and in fermentative and
      nonfermentative gram-negative bacteria. Escherichia coli sequence type (ST) 101
      was most commonly found, reflecting a common global relationship between ST101
      and NDM-1. 

PMID- 25989321
TI  - TiC/NiO Core/Shell Nanoarchitecture with Battery-Capacitive Synchronous Lithium
      Storage for High-Performance Lithium-Ion Battery.
AB  - The further development of electrode materials with high capacity and excellent
      rate capability presents a great challenge for advanced lithium-ion batteries.
      Herein, we demonstrate a battery-capacitive synchronous lithium storage mechanism
      based on a scrupulous design of TiC/NiO core/shell nanoarchitecture, in which the
      TiC nanowire core exhibits a typical double-layer capacitive behavior, and the
      NiO nanosheet shell acts as active materials for Li(+) storage. The as
      constructed TiC/NiO (32 wt % NiO) core/shell nanoarchitecture offers high overall
      capacity and excellent cycling ability, retaining above 507.5 mAh g(-1)
      throughout 60 cycles at a current density of 200 mA g(-1) (much higher than
      theoretical value of the TiC/NiO composite). Most importantly, the high rate
      capability is far superior to that of NiO or other metal oxide electrode
      materials, owing to its double-layer capacitive characteristics of TiC nanowire
      and intrinsic high electrical conductivity for facile electron transport during
      Li(+) storage process. Our work offers a promising approach via a rational
      hybridization of two electrochemical energy storage materials for harvesting high
      capacity and good rate performance. 

PMID- 25989322
TI  - Temperature management in neurological and neurosurgical intensive care unit.

PMID- 25989323
TI  - Two-Stage Single-Compartment Models to Evaluate Dissolution in the Lower
      Intestine.
AB  - The purpose was to propose two-stage single-compartment models for evaluating
      dissolution characteristics in distal ileum and ascending colon, under conditions
      simulating the bioavailability and bioequivalence studies in fasted and fed state
      by using the mini-paddle and the compendial flow-through apparatus (closed-loop
      mode). Immediate release products of two highly dosed active pharmaceutical
      ingredients (APIs), sulfasalazine and L-870,810, and one mesalamine colon
      targeting product were used for evaluating their usefulness. Change of medium
      composition simulating the conditions in distal ileum (SIFileum ) to a medium
      simulating the conditions in ascending colon in fasted state and in fed state was
      achieved by adding an appropriate solution in SIFileum . Data with immediate
      release products suggest that dissolution in lower intestine is substantially
      different than in upper intestine and is affected by regional pH differences >
      type/intensity of fluid convection > differences in concentration of other
      luminal components. Asacol(r) (400 mg/tab) was more sensitive to type/intensity
      of fluid convection. In all the cases, data were in line with available human
      data. Two-stage single-compartment models may be useful for the evaluation of
      dissolution in lower intestine. The impact of type/intensity of fluid convection
      and viscosity of media on luminal performance of other APIs and drug products
      requires further exploration.

PMID- 25989324
TI  - Levosimendan Reduces Mortality in Adults with Left Ventricular Dysfunction
      Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis.
AB  - INTRODUCTION: Levosimendan is implemented in patients with low cardiac output
      after cardiac surgery. However, the strength of evidence is limited by randomized
      controlled trials enrolling a small number of patients. Hence we have conducted a
      systematic review to determine the role of levosimendan in adult cardiac surgery.
      METHODS: PUBMED, WoS, Cochrane database, and SCOPUS were systematically queried
      to identify original English language peer-reviewed literature (inception-October
      2014) comparing clinical results of adult cardiac surgery between levosimendan
      and control. Pooled odds ratio (OR) was calculated using the Peto method; p <
      0.05 is significant; results are presented within 95% confidence intervals.
      Continuous data was compared using standardized mean difference/mean difference.
      RESULTS: Fourteen studies were included in the analysis. Levosimendan reduced
      early mortality in patients with reduced ejection fraction (5.5% vs. 9.1%) (OR
      0.48 [0.23-0.76]; p = 0.004). This result was confirmed using sensitivity
      analysis. Postoperative acute renal failure was lower with levosimendan therapy
      (7.4% vs. 11.5%). Intensive care unit stay was shorter in the levosimendan cohort
      comparable in both groups (standardized mean difference -0.31 [-0.53, -0.09]; p =
      0.006; I(2)  = 33.6%). Levosimendan-treated patients stayed 1.01 (1.61-0.42) days
      shorter when compared to control (p = 0.001). CONCLUSION: Our meta-analysis
      demonstrates that Levosimendan improves clinical outcomes in patients with left
      ventricular dysfunction undergoing cardiac surgery. Results of the ongoing
      multicenter randomized controlled trial are awaited to provide more conclusive
      evidence regarding the benefit of this drug.

PMID- 25989325
TI  - Multi-criterion water quality analysis of the Danube River in Serbia: A
      visualisation approach.
AB  - River quality analysis is an important activity which, in Serbia, has been
      performed using the Serbian Water Quality Index (SWQI). This is a measure based
      on a weighted aggregation of 10 water quality parameters. In this work,
      alternative methods drawing on visualisation approaches used in multi-criterion
      decision analysis are applied to the problem of evaluating river quality in the
      Danube. Two methods are considered: one which constructs a graph using the
      dominance relation combined with a further multi-criterion ranking method,
      average rank, and the other in which the dimensionality of the data is reduced
      using PCA for visualisation. Results for data collected in 2010 are analysed and
      compared with the corresponding SWQI values for the river in that year, and we
      find that by employing these methods it is possible to reveal more information
      within the data than is possible by using SWQI alone. 

PMID- 25989326
TI  - Editorial.

PMID- 25989327
TI  - Bounded in a nutshell and a king of infinite space: the embodied self and its
      intentional world.
AB  - This paper explores the implications of developments in phenomenological biology
      for a reconsideration of synchronicity and the self. The enactive approach of
      Maturana and Varela aims to reformulate the relation between biological organisms
      and the world in a non-Cartesian way, breaking down the conceptual division
      between mind and world so that meaning can be seen as a function of the species
      specific way in which an organism engages with its environment. This leads to a
      view of the self as inherently embodied and engaged with the particularities of
      its material, cultural and social worlds, while being infinitely extended through
      the power of imagination; this enables humans to adapt to many different social
      and material environments. In order to understand these differences, we need to
      'enter into the world of the other'. Where understanding of other animals
      requires immersion in their environmental milieux, understanding other humans
      requires us also to recognize that differences in socio-cultural milieux create
      significantly different worlds of meaning and experience. 

PMID- 25989328
TI  - The correspondence between Erich Neumann and C.G. Jung on the occasion of the
      November, progroms 1938 [corrected].
AB  - In the light of recently-published correspondence between Jung and Neumann, this
      paper considers and connects two aspects of their relationship: Jung's theory of
      an ethno-specific differentiation of the unconscious as formulated in 1934, and
      the relationship between Jung and Neumann at the beginning of the Holocaust in
      1938-with Jung as the wise old man and a father figure on one hand, and Neumann
      as the apprentice and dependent son on the other. In examining these two issues,
      a detailed interpretation of four letters, two by Neumann and two by Jung,
      written in 1938 and 1939, is given. Neumann's reflections on the collective
      Jewish determination in the face of the November pogroms in 1938 led Jung to
      modify his view, with relativization and secularization of his former position.
      This shift precipitated a deep crisis with feelings of disorientation and
      desertion in Neumann; the paper discusses how a negative father complex was then
      constellated and imaged in a dream. After years of silence, the two men were able
      to renew the deep bonds that characterized their lifelong friendship. 

PMID- 25989329
TI  - Temporality and the torments of time.
AB  - Immersion in time gives birth to consciousness, as well as conflict and torment.
      When human beings developed a sense of future, they also gained the ability to
      anticipate threats from nature or their fellow beings. They thereby created
      cultures that are bastions of survival, as well as places of poetry, art and
      religion where they could band together and reflect upon their common plight. The
      practice of psychoanalysis is in many ways a temporal process, a process of
      remembering, for owning and elaborating a past that gives us substance, thereby
      providing a basis for reflective consciousness. Stimulated by Freud's early
      writings, Lacan, Laplanche and their successors in particular have focussed
      extensively on time and psychoanalysis, and their views are a central point of
      this discussion. A substantial case study is offered that provides concrete
      examples of these perspectives. A multi-faceted view of temporality emerges, one
      that is more syncopated than linear or teleological. In conclusion, I will
      briefly discuss recent findings in the neuroscience of memory and 'time travel'
      that underpin contemporary psychoanalytic ideas in surprising ways. It is
      important to remember that acceptance of the contradictory nature of temporal
      experience can open space for increased freedom and playfulness. 

PMID- 25989330
TI  - Saying goodbye to the hero: Jung, Liber Novus and conversion from addiction.
AB  - Two chapters in Liber Novus throw fresh light on Jung's epistemology of
      addiction. Taking these as a starting point, the nature of the challenges that
      patients confront in leaving addiction behind are explored. It is suggested that
      an archetypal process of separation is constellated at the point of quitting as
      the precursor to a life without the object of the addiction. A short account is
      given of Jung's part in the inception of Alcoholics Anonymous and the potential
      role of a 'conversion experience' as an initiation into psychological
      reorientation away from the negative individuation experienced by the hero. The
      case of a patient addicted to heroin illustrates the contribution of an analytic
      approach in an NHS setting, along with other workers in a rehabilitation centre.
      Certain challenges of working with addicted people are outlined, including
      arousal of the psychotherapist's rescue fantasies. 

PMID- 25989331
TI  - The seventh penis: towards effective psychoanalytic work with pre-surgical
      transsexuals.
AB  - The author reflects on his contrasting analytic work with two transsexual
      patients. He uses three previous psychoanalytic studies (Stoller, Morel and
      Lemma) to explore whether effective analytic work with the issues driving a
      person's determined wish for sex reassignment surgery (SRS) is possible.
      Particular consideration is given to how such work might navigate a path between
      traumatizing and pathologizing the patient on the one hand and avoiding important
      analytic material out of fear of so doing on the other. The author proceeds to
      ask whether it is possible to tell in advance, with any degree of reliability,
      who is and who is not likely to benefit from surgery. He considers certain
      diagnostic issues in relation to these questions. Illustrations are given of how,
      in practice, countertransference anxieties about psychopathologizing transsexual
      patients can contribute to significant difficulties in working clinically with
      them. It is argued that the understanding and containment of such anxieties could
      eventually lead to more effective analytic work, and that such work might be
      further facilitated by considering the contribution of mind-body dissociation to
      transsexualism. 

PMID- 25989332
TI  - A response to Robert Withers.

PMID- 25989336
TI  - Demographics and disease characteristics of patients with psoriasis enrolled in
      the British Association of Dermatologists Biologic Interventions Register.
AB  - BACKGROUND: The British Association of Dermatologists Biologic Interventions
      Register (BADBIR) is a prospective, observational cohort designed to assess the
      long-term safety of biologic and conventional systemic therapies used for adults
      with moderate-to-severe psoriasis in the U.K. and Republic of Ireland.
      OBJECTIVES: To describe the demographics, disease severity and comorbidities of
      patients with psoriasis on enrolment into BADBIR, and to highlight differences in
      those commencing biologics compared with those on conventional systemic
      therapies. METHODS: Baseline data were collected from 151 dermatology departments
      in the U.K. and Republic of Ireland. Descriptive analysis was conducted. RESULTS:
      As of August 2014, 8399 patients were registered with BADBIR; 5065 (60%) received
      biologics, of whom 52.8% received adalimumab, 24.6% etanercept, 18.7% ustekinumab
      and 3.9% infliximab. In the comparator cohort 44.1% received methotrexate, 23.1%
      ciclosporin, 18.0% acitretin and 7.6% fumaric acid esters. Overall 4897 (58%)
      were male. Patients on biologics had a higher mean +/- SD age and disease
      duration than patients on conventional systemic therapies (46.3 +/- 12.7 vs. 44.3
      +/- 14.3 years and 23.0 +/- 12.6 vs. 19.0 +/- 13.4 years, respectively; both P <
      0.001). Mean body mass index, Psoriasis Area and Severity Index and Dermatology
      Life Quality Index scores for patients on biologics were higher than for those on
      conventional systemic therapies (31.0 +/- 7.2 vs. 30.1 +/- 7.3 kg m(-2) ; 16.4 +/
      8.3 vs. 15.5 +/- 7.9 and 17.4 +/- 7.5 vs. 15.0 +/- 7.1, respectively; all P <
      0.001). In total 71% of all patients had comorbidities and 47% had more than one
      comorbidity. The most frequent comorbidities were obesity (42.1%), hypertension
      (25.7%), depression (22.1%) and psoriatic arthritis (17.1%). CONCLUSIONS: BADBIR
      is an invaluable resource to study the safety and effectiveness of both biologic
      and conventional systemic therapies. Understanding differences in baseline
      characteristics between cohorts is crucial in undertaking future
      pharmacovigilance studies.

PMID- 25989338
TI  - Briakinumab for treatment of Crohn's disease: results of a randomized trial.
AB  - BACKGROUND: This study assessed the efficacy and safety of briakinumab, a human
      anti-IL-12/23p40 monoclonal antibody, compared with placebo for the induction and
      maintenance of remission in patients with moderately to severely active Crohn's
      disease. METHODS: In this phase 2b, multicenter, double-blind, parallel group
      study, 246 patients stratified by prior tumor necrosis factor-antagonist use and
      response, were randomized (1:1:1:3) to 4 intravenous induction regimens: placebo,
      200, 400, or 700 mg briakinumab, at weeks 0/4/8. At week 12, responders in the
      placebo or 400-mg induction groups entered the maintenance phase with the same
      regimen, whereas responders in the 700-mg induction group were rerandomized
      (1:1:1) to receive placebo, 200, or 700 mg briakinumab at weeks 12/16/20. At week
      24, patients in remission stopped receiving study drug (withdrawal phase) until
      relapse. Patients experiencing relapse, nonresponders, and nonremitters could
      enter the open-label phase. RESULTS: The primary end point of clinical remission
      at week 6 was not met. There were numerically greater rates of remission and
      response at 6, 12, or 24 weeks in patients treated with briakinumab. The safety
      and tolerability profile of briakinumab was similar in the induction and
      maintenance phases of the trial. CONCLUSIONS: Briakinumab showed a similar safety
      and tolerability profile to placebo in the induction and maintenance phases, and
      comparable rates of serious adverse events, adverse events leading to
      discontinuation, and malignancy. These data provide support for the potential
      efficacy of briakinumab and other IL-12/23 inhibitors in the treatment of
      moderate-to-severe Crohn's disease.

PMID- 25989337
TI  - Quality of methods reporting in animal models of colitis.
AB  - BACKGROUND: Current understanding of the onset of inflammatory bowel diseases
      relies heavily on data derived from animal models of colitis. However, the
      omission of information concerning the method used makes the interpretation of
      studies difficult or impossible. We assessed the current quality of methods
      reporting in 4 animal models of colitis that are used to inform clinical research
      into inflammatory bowel disease: dextran sulfate sodium, interleukin-10, CD45RB T
      cell transfer, and 2,4,6-trinitrobenzene sulfonic acid (TNBS). METHODS: We
      performed a systematic review based on PRISMA guidelines, using a PubMed search
      (2000-2014) to obtain publications that used a microarray to describe gene
      expression in colitic tissue. Methods reporting quality was scored against a
      checklist of essential and desirable criteria. RESULTS: Fifty-eight articles were
      identified and included in this review (29 dextran sulfate sodium, 15 interleukin
      10, 5 T cell transfer, and 16 TNBS; some articles use more than 1 colitis model).
      A mean of 81.7% (SD = +/-7.038) of criteria were reported across all models. Only
      1 of the 58 articles reported all essential criteria on our checklist. Animal
      age, gender, housing conditions, and mortality/morbidity were all poorly
      reported. CONCLUSIONS: Failure to include all essential criteria is a cause for
      concern; this failure can have large impact on the quality and replicability of
      published colitis experiments. We recommend adoption of our checklist as a
      requirement for publication to improve the quality, comparability, and
      standardization of colitis studies and will make interpretation and translation
      of data to human disease more reliable.

PMID- 25989339
TI  - Predictors of ICU Admission and Outcomes 1 Year Post-Admission in Persons with
      IBD: A Population-based Study.
AB  - BACKGROUND: To determine predictors of intensive care unit (ICU) admission and to
      assess health care utilization (HCU) post-ICU admission among persons with
      inflammatory bowel disease (IBD). METHODS: We matched a population-based database
      of Manitobans with IBD to a general population cohort on age, sex, and region of
      residence and linked these cohorts to a population-based ICU database. We
      compared the incidence rates of ICU admission among prevalent IBD cases according
      to HCU in the year before admission using generalized linear models adjusting for
      age, sex, socioeconomic status, region, and comorbidity. Among incident cases of
      IBD who survived their first ICU admission, we compared HCU with matched controls
      who survived ICU admission. RESULTS: Risk factors for ICU admission from the year
      before admission included cumulative corticosteroid use (incidence rate ratio,
      1.006 per 100 mg of prednisone; 95% confidence interval, 1.004-1.008) and IBD
      related surgery (incidence rate ratio, 2.79; 95% confidence interval, 1.99-3.92).
      Use of immunomodulatory therapies within 1 year, or surgery for IBD beyond 1 year
      prior, were not associated with ICU admission. In those who used corticosteroids
      and immunomodulatory medications in the year before ICU admission, the use of
      immunomodulatory medications conferred a 30% risk reduction in ICU admission
      (incidence rate ratio, 0.70; 95% confidence interval, 0.50-0.97). Persons with
      IBD who survived ICU admission had higher HCU in the year following ICU discharge
      than controls. CONCLUSIONS: Corticosteroid use and surgery within the year are
      associated with ICU admission in IBD while immunomodulatory therapy is not.
      Surviving ICU admission is associated with high HCU in the year post-ICU
      discharge.

PMID- 25989340
TI  - Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical
      Decision-making for IBD Outpatients on Maintenance Infliximab Therapy.
AB  - BACKGROUND: Infliximab is an effective therapy for inflammatory bowel disease
      (IBD). However, more than 50% of patients lose response. Empiric dose
      intensification is not effective for all patients because not all patients have
      objective disease activity or subtherapeutic drug level. The aim was to determine
      how an objective marker of disease activity or therapeutic drug monitoring
      affects clinical decisions regarding maintenance infliximab therapy in
      outpatients with IBD. METHODS: Consecutive patients with IBD on maintenance
      infliximab therapy were invited to participate by providing preinfusion stool and
      blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were
      measured by enzyme linked immunosorbent assay. Three decisions were compared: (1)
      actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert
      panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c)
      clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves
      were used to assess the ability of FCP and ITL in predicting clinical disease
      activity or remission. RESULTS: A total of 36 sets of blood and stool were
      available for analysis; median FCP 191.5 MUg/g, median ITLs 7.3 MUg/mL. The
      actual clinical decision differed from the hypothetical decision in 47.2% (FCP
      algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4%
      (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL)
      cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95%
      confidence interval [CI], 0.197-0.641) and subtherapeutic ITL (AUC = 0.774; 95%
      CI, 0.536-1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254
      0.742) and objective remission (AUC = 0.773; 95% CI, 0.622-0.924). CONCLUSIONS:
      Using FCP and ITLs in addition to clinical data results in an increased number of
      decisions to optimize management in outpatients with IBD on stable maintenance
      infliximab therapy.

PMID- 25989342
TI  - Symptoms of Depression and Risk of New Episodes of Low Back Pain: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: To investigate the contribution of symptoms of depression to future
      episodes of low back pain (LBP). METHODS: A search was conducted of AMED, CINAHL,
      Embase, Health and Society (H&S), LILACS, MEDLINE, PsycINFO, Scopus, and Web of
      Science databases. We included cohort studies investigating the effect of
      symptoms of depression on the development of new episodes of LBP, either lifetime
      incidence or a recurrent episode, in a population free of LBP at baseline. We
      accepted the original study's definition for a new episode of LBP, and for
      classifying patients as LBP-free at study entry. Two independent investigators
      extracted data and assessed methodological quality. Meta-analyses with random
      effects were used to pool risk estimates. RESULTS: We included 19 studies, with
      11 incorporated in the meta-analyses. Overall pooled results showed that symptoms
      of depression increased the risk of developing LBP (odds ratio [OR] 1.59, 95%
      confidence interval [95% CI] 1.26-2.01). The risk was similar in studies that
      used the diagnostic interview method (OR 1.66, 95% CI 1.14-2.42) and in studies
      using self-report screening questionnaires (OR 1.68, 95% CI 1.05-2.70). No
      statistically significant relationship was observed when we pooled studies that
      employed nonspecific screening questionnaires (OR 1.17, 95% CI 0.48-2.87). Three
      studies provided results in incremental categories of symptoms of depression and
      the pooled OR for the most severe level of depression (OR 2.51, 95% CI 1.58-3.99)
      was higher than for the lowest level (OR 1.51, 95% CI 0.89-2.56). CONCLUSION:
      Individuals with symptoms of depression have an increased risk of developing an
      episode of LBP in the future, with the risk being higher in patients with more
      severe levels of depression.

PMID- 25989341
TI  - Minimally invasive surgery for inflammatory bowel disease.
AB  - Surgical management of inflammatory bowel disease is a challenging endeavor given
      infectious and inflammatory complications, such as fistula, and abscess, complex
      often postoperative anatomy, including adhesive disease from previous open
      operations. Patients with Crohn's disease and ulcerative colitis also bring to
      the table the burden of their chronic illness with anemia, malnutrition, and
      immunosuppression, all common and contributing independently as risk factors for
      increased surgical morbidity in this high-risk population. However, to reduce the
      physical trauma of surgery, technologic advances and worldwide experience with
      minimally invasive surgery have allowed laparoscopic management of patients to
      become standard of care, with significant short- and long-term patient benefits
      compared with the open approach. In this review, we will describe the current
      state-of the-art for minimally invasive surgery for inflammatory bowel disease
      and the caveats inherent with this practice in this complex patient population.
      Also, we will review the applicability of current and future trends in minimally
      invasive surgical technique, such as laparoscopic "incisionless," single-incision
      laparoscopic surgery (SILS), robotic-assisted, and other techniques for the
      patient with inflammatory bowel disease. There can be no doubt that minimally
      invasive surgery has been proven to decrease the short- and long-term burden of
      surgery of these chronic illnesses and represents high-value care for both
      patient and society. 

PMID- 25989343
TI  - Redox-Sensitive Polymer/SPIO Nanocomplexes for Efficient Magnetofection and MR
      Imaging of Human Cancer Cells.
AB  - Magnetofection has received increasing attention for its great potential on gene
      therapy. To promote its clinical therapeutic applications, development of safe
      and effective magnetic nanocarriers is in high demand. Herein, we present a redox
      sensitive polymer/metal nanocomplex system (PSPIO) for efficient magnetofection
      and magnet resonance imaging (MRI) on cancer cells. PSPIO was prepared by
      modifying SPIO with redox-sensitive polyethylenimine (SSPEI) via a ligand
      exchange process. PSPIO could efficiently condense plasmid DNA (pDNA) into
      nanoparticles, which exhibited several favorable properties for gene delivery,
      including protection of nucleic acids from enzymatic degradation, stable colloids
      in serum, and redox-responsive pDNA release. As a potential MR imaging agent,
      PSPIO displayed good magnetization (28.3 emu/g) and dose-dependent T2-weighted
      imaging contrast (R2 = 291.1 s(-1) mM(-1)) in vitro. The use of redox-sensitive
      SSPEI polymer contributed to much lower cytotoxicity of PSPIO compared to
      nondegradable bPEI25k. In vitro transfection efficiency of PSPIO was
      significantly enhanced under an external magnetic field. In the presence of
      serum, PSPIO exhibited higher transgene expression than SSPEI or bPEI25k polymer
      on mouse glioma (ALTS1C1) or human prostate cancer (PC3) cell lines. Taken
      together, it is demonstrated that PSPIO possess great potential for cancer gene
      therapy and molecular imaging. 

PMID- 25989344
TI  - Chromodomain protein Tcd1 is required for macronuclear genome rearrangement and
      repair in Tetrahymena.
AB  - The survival of an organism's progeny depends on the maintenance of its genome.
      Programmed DNA rearrangement and repair in Tetrahymena occur during the
      differentiation of the developing somatic macronuclear genome from the germ line
      micronuclear genome. Tetrahymena chromodomain protein (Tcd1) exhibited dynamic
      localization from the parental to the developing macronuclei. In the developing
      macronuclei, Tcd1 colocalized with Pdd1 and H3K9me3. Furthermore, Tcd1
      colocalized with Pdd1 in the conjusome and "donut structure" of DNA elimination
      heterochromatin region. During the growth and conjugation stages, TCD1 knockout
      cells appeared normal and similar to wild-type strains. In addition, these
      knockout cells proceeded to the 2MAC-1MIC stage. However, the progeny of the TCD1
      knockout cells did not grow upon return to SPP medium and eventually died. The
      deletion of the internal elimination sequence R element was partially disrupted
      in the developing new macronuclei. Gamma H2A staining showed that Tcd1 loss
      induced the accumulation of DNA double-strand breaks and the failure of genome
      repair. These results suggest that the chromodomain protein Tcd1 is required for
      the rearrangement and repair of new macronuclear genome in Tetrahymena. 

PMID- 25989345
TI  - A facile synthesis of novel miconazole analogues and the evaluation of their
      antifungal activity.
AB  - Four novel miconazole analogues (8-11) were synthetized and evaluated for
      activity against four filamentous fungi (Mucor hiemalis, Aspergillus fumigatus,
      Trichosporon cutaneum, and Rhizopus oryzae) and eight species of Candida as yeast
      specimens. Compounds 9 and 10 showed very good activity when evaluated in yeast
      (MIC 0.112 and 0.163 MUg/mL) compared to the reference compound, itraconazole
      (MIC 0.067 MUg/mL). The best antifungal activity in filamentous strains was shown
      by compound 9. Hence compounds 9 and 10 represent new leads for further
      pharmacomodulation in this series. 

PMID- 25989346
TI  - Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their
      Abundance of Antigenic Regions (AAR).
AB  - Excretory/Secretory (ES) proteins play an important role in the host-parasite
      interactions. Experimental identification of ES proteins is time-consuming and
      expensive. Alternative bioinformatics approaches are cost-effective and can be
      used to prioritize the experimental analysis of therapeutic targets for parasitic
      diseases. Here we predicted and functionally annotated the ES proteins in T.
      solium genome using an integration of bioinformatics tools. Additionally, we
      developed a novel measurement to evaluate the potential antigenicity of T. solium
      secretome using sequence length and number of antigenic regions of ES proteins.
      This measurement was formalized as the Abundance of Antigenic Regions (AAR)
      value. AAR value for secretome showed a similar value to that obtained for a set
      of experimentally determined antigenic proteins and was different to the
      calculated value for the non-ES proteins of T. solium genome. Furthermore, we
      calculated the AAR values for known helminth secretomes and they were similar to
      that obtained for T. solium. The results reveal the utility of AAR value as a
      novel genomic measurement to evaluate the potential antigenicity of secretomes.
      This comprehensive analysis of T. solium secretome provides functional
      information for future experimental studies, including the identification of
      novel ES proteins of therapeutic, diagnosis and immunological interest. 

PMID- 25989347
TI  - Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in
      Straight Microchannels.
AB  - Viscoelasticity-induced particle migration has recently received increasing
      attention due to its ability to obtain high-quality focusing over a wide range of
      flow rates. However, its application is limited to low throughput regime since
      the particles can defocus as flow rate increases. Using an engineered carrier
      medium with constant and low viscosity and strong elasticity, the sample flow
      rates are improved to be 1 order of magnitude higher than those in existing
      studies. Utilizing differential focusing of particles of different sizes, here,
      we present sheathless particle/cell separation in simple straight microchannels
      that possess excellent parallelizability for further throughput enhancement. The
      present method can be implemented over a wide range of particle/cell sizes and
      flow rates. We successfully separate small particles from larger particles, MCF-7
      cells from red blood cells (RBCs), and Escherichia coli (E. coli) bacteria from
      RBCs in different straight microchannels. The proposed method could broaden the
      applications of viscoelastic microfluidic devices to particle/cell separation due
      to the enhanced sample throughput and simple channel design. 

PMID- 25989349
TI  - A thermal expansion investigation of the melting point anomaly in
      trihalomesitylenes.
AB  - Generally the order of melting point of halogenated compounds is found to be I >
      Br > Cl whereas, in the series of trihalomesitylenes the order follows as Br > I
      ~ Cl. This melting point anomaly has been explained in terms of their thermal
      expansion behaviours. The order of thermal expansion in this series is found to
      be Br < I ~ Cl. 

PMID- 25989350
TI  - Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute
      Stroke.
AB  - BACKGROUND: Patients with certain types of stroke need urgent anticoagulation and
      it is extremely important for them to achieve fast and stable anticoagulant
      effect and receive individualized treatment during the initiation of warfarin
      therapy. METHODS: We conducted a prospective study among 210 acute stroke
      patients who had an indication for anticoagulation and compared the impact of
      CYP2C9 and VKORC1 genotype-guided warfarin dosing (PhG) with fixed dosing (NPhG)
      on anticoagulation control and clinical outcome between groups. RESULTS: PhG
      achieved target INR values earlier, i.e., on average in 4.2 (4.1-4.7, 95% CI)
      days compared to NPhG (5.2 days [4.7-6.4, 95% CI]) (p = 0.0009), spent a higher
      percentage of time in the therapeutic INR range (76.3% [74.7-78.5, 95% CI] vs.
      67.1% [64.5-69.6, 95% CI] in NPhG), and spent less time overdosed (INR > 3.1)
      (PhG 0.4 [0.1-0.7, 95% CI], NPhG 1.7 [1.1-2.3, 95% CI] days; p >0.000). PhG
      reached stable maintenance dose faster (10 [9.9-10.7, 95% CI] vs. 13.9 [13.3
      14.7, 95% CI] days in controls; p = 0.0049) and had a better clinical outcome in
      relation to neurological deficit on admission as compared to NPhG. CONCLUSION: We
      confirmed that warfarin therapy with genotype-guided dosing instead of fixed
      dosing reduces the time required for stabilization and improves anticoagulant
      control with better clinical outcome in early stages of warfarin therapy
      introduction among acute stroke patients, which is essential for clinical
      practice.

PMID- 25989351
TI  - Prognostic Value of the Percentage of Neutrophils on Admission in Patients with
      ST-elevated Myocardial Infarction Undergoing Primary Percutaneous Coronary
      Intervention.
AB  - BACKGROUND AND AIMS: An elevated neutrophil count or neutrophil/lymphocyte ratio
      on admission has been reported to be an independent predictor of adverse cardiac
      events in patients with acute coronary syndrome (ACS). The relationship between
      the percentage of neutrophils (N%) at the time of admission and the long-term
      outcomes in patients with ST-segment elevated myocardial infarction (STEMI) who
      have undergone primary percutaneous coronary intervention (PCI) remains unclear.
      The aim of this study was to investigate the usefulness of the admission N% in
      predicting long-term mortality in patients with STEMI who were undergoing primary
      PCI. METHODS: We evaluated 701 consecutive patients admitted to nine medical
      institutions in northwest China within 24 h after symptom onset from January 1,
      2009-December 31, 2011. Using a receiver-operating characteristic analysis, N%
      >=82.1% was the best predictor of long-term mortality. Patients were divided into
      two groups according to this criterion. Mean follow-up time was 39.03 months.
      RESULTS: The long-term all-cause mortality rate was significantly higher in
      patients with a high N% level (7.17 vs. 3.11%, p = 0.015) as was the rate of
      cardiac mortality (6.48 vs. 2.59%, p = 0.013). In a multivariate logistic
      analysis, a high N% level was an independent predictor of long-term all-cause
      mortality (odds ratio 2.59, 95% confidence interval 1.21-5.53, p = 0.002) and
      long-term cardiac mortality (odds ratio 2.79, 95% confidence interval 1.24-6.28,
      p = 0.013). CONCLUSIONS: A high N% level on admission is an independent predictor
      of long-term mortality in STEMI patients undergoing primary PCI.

PMID- 25989352
TI  - B-cell epitope spreading and inflammation in a mouse model of arthritis is
      associated with a deficiency in reactive oxygen species production.
AB  - Autoantibody-mediated inflammation contributes to the development of rheumatoid
      arthritis (RA), and anti-type II collagen (CII) antibodies are present in the
      serum, synovial fluid, and cartilage of RA patients. We had previously generated
      and characterized knock-in mice expressing a germline-encoded, CII-specific IgH
      (B10Q.ACB), which demonstrated positive selection of self-reactive B cells. Here,
      we show that despite the spontaneous production of CII-specific autoantibodies,
      B10Q.ACB mice are protected from collagen-induced arthritis. Introducing a
      mutation in the Ncf1 gene, leading to ROS deficiency, breaks this strong
      arthritis resistance. Disease development in Ncf1-mutated B10Q.ACB mice is
      associated with an enhanced germinal center formation but without somatic
      mutations of the auto-reactive B cells, increased T-cell responses and
      intramolecular epitope-spreading. Thus, ROS-mediated B-cell tolerance to a self
      antigen could operate by limiting the expansion of the auto-reactive B-cell
      repertoire, which has important implications for the understanding of epitope
      spreading phenomena in rheumatoid arthritis and other autoimmune diseases. 

PMID- 25989348
TI  - Adaptable hydrogel networks with reversible linkages for tissue engineering.
AB  - Adaptable hydrogels have recently emerged as a promising platform for three
      dimensional (3D) cell encapsulation and culture. In conventional, covalently
      crosslinked hydrogels, degradation is typically required to allow complex
      cellular functions to occur, leading to bulk material degradation. In contrast,
      adaptable hydrogels are formed by reversible crosslinks. Through breaking and re
      formation of the reversible linkages, adaptable hydrogels can be locally modified
      to permit complex cellular functions while maintaining their long-term integrity.
      In addition, these adaptable materials can have biomimetic viscoelastic
      properties that make them well suited for several biotechnology and medical
      applications. In this review, an overview of adaptable-hydrogel design
      considerations and linkage selections is presented, with a focus on various cell
      compatible crosslinking mechanisms that can be exploited to form adaptable
      hydrogels for tissue engineering. 

PMID- 25989353
TI  - Stigma as a barrier to treatment for child acute malnutrition in Marsabit County,
      Kenya.
AB  - Acute malnutrition affects millions of children each year, yet global coverage of
      life-saving treatment through the community-based management of acute
      malnutrition (CMAM) is estimated to be below 15%. We investigated the potential
      role of stigma as a barrier to accessing CMAM. We surveyed caregivers bringing
      children to rural health facilities in Marsabit County, Kenya, divided into three
      strata based on the mid-upper arm circumference of the child: normal status (n =
      327), moderate acute malnutrition (MAM, n = 241) and severe acute malnutrition
      (SAM, n = 143). We used multilevel mixed effects logistic regression to estimate
      the odds of reporting shame as a barrier to accessing health care. We found that
      the most common barriers to accessing child health care were those known to be
      universally problematic: women's time and labour constraints. These constituted
      the top five most frequently reported barriers regardless of child acute
      malnutrition status. In contrast, the odds of reporting shame as a barrier were
      3.64 (confidence interval: 1.66-8.03, P < 0.05) times higher in caregivers of MAM
      and SAM children relative to those of normal children. We conclude that stigma is
      an under-recognized barrier to accessing CMAM and may constrain programme
      coverage. In light of the large gap in coverage of CMAM, there is an urgent need
      to understand the sources of acute malnutrition-associated stigma and adopt
      effective means of de-stigmatization.

PMID- 25989354
TI  - Enhanced Amplified Spontaneous Emission in Perovskites Using a Flexible
      Cholesteric Liquid Crystal Reflector.
AB  - Organic-inorganic perovskites are highly promising solar cell materials with
      laboratory-based power conversion efficiencies already matching those of
      established thin film technologies. Their exceptional photovoltaic performance is
      in part attributed to the presence of efficient radiative recombination pathways,
      thereby opening up the possibility of efficient light-emitting devices. Here, we
      demonstrate optically pumped amplified spontaneous emission (ASE) at 780 nm from
      a 50 nm-thick film of CH3NH3PbI3 perovskite that is sandwiched within a cavity
      composed of a thin-film (~7 MUm) cholesteric liquid crystal (CLC) reflector and a
      metal back-reflector. The threshold fluence for ASE in the perovskite film is
      reduced by at least two orders of magnitude in the presence of the CLC reflector,
      which results in a factor of two reduction in threshold fluence compared to
      previous reports. We consider this to be due to improved coupling of the oblique
      and out-of-plane modes that are reflected into the bulk in addition to any
      contributions from cavity modes. Furthermore, we also demonstrate enhanced ASE on
      flexible reflectors and discuss how improvements in the quality factor and
      reflectivity of the CLC layers could lead to single-mode lasing using CLC
      reflectors. Our work opens up the possibility of fabricating widely wavelength
      tunable "mirror-less" single-mode lasers on flexible substrates, which could find
      use in applications such as flexible displays and friend or foe identification. 

PMID- 25989355
TI  - Perceptions and Attitudes Toward NANDA-I Nursing Diagnoses: A Cross-Sectional
      Study of Jordanian Nursing Students.
AB  - PURPOSE: To assess the perceptions and attitudes of undergraduate nursing
      students toward NANDA-I nursing diagnosis. METHODS: A descriptive cross-sectional
      design was used. A convenient sample was recruited from nursing students at Zarqa
      University/Jordan. Perceptions toward NANDA-I Nursing Diagnosis scale and
      Positions on Nursing Diagnosis scale were used. FINDINGS: A total of 101 nursing
      students were included. A correct perception toward NANDA-I nursing diagnosis was
      evident. Attitudes toward NANDA appeared positive. However, insufficient
      distinction between nursing diagnosis and medical diagnosis and feeling less
      comfort while using NANDA-I were reported. CONCLUSIONS: Nursing students showed
      correct perceptions and positive attitudes toward the application of NANDA-I.
      PRACTICE IMPLICATIONS: Proper implementation of NANDA-I is a prerequisite to the
      better understanding of nursing language.

PMID- 25989357
TI  - Distinctive Reaction Pathways at Base Metals in High-Spin Organometallic
      Catalysts.
AB  - Inexpensive "base" metals are more affordable and sustainable than precious
      metals and also offer opportunities to discover new mechanisms for selective
      catalytic reactions. Base metal complexes can have high-spin electronic
      configurations that are rare in precious metal complexes. This Account describes
      some concepts relevant to high-spin organometallic complexes, focusing on our
      recent work with beta-diketiminate complexes of iron and cobalt. Even though high
      spin organometallic complexes have some unfamiliar spectroscopic properties, they
      can be studied using NMR spectroscopy as well as techniques that focus on the
      magnetism brought about by the unpaired electrons. Understanding the mechanisms
      of reactions using these complexes can be complicated, because complexes with a
      high-spin electronic configuration may need to change spin states to avoid high
      barriers for reaction. These spin-state changes can be rapid, and the ability of
      an excited spin state to "cut through" the barrier for a reaction can lead to
      spin acceleration. These concepts, originally developed by Poli, Shaik, Schwarz,
      and Harvey, are applied here to the fundamental organometallic reaction of beta
      hydride elimination (BHE). Experimentally validated density-functional
      calculations show spin acceleration in BHE using three-coordinate iron(II) and
      cobalt(II) complexes. A square-planar transition state is particularly beneficial
      for accelerating BHE when a high-spin iron(II) complex goes from an S = 2 ground
      state to an S = 1 transition state or when a high-spin cobalt(II) complex goes
      from an S = 3/2 ground state to an S = 1/2 transition state. The relative
      energies of the spin states can be controlled with the choice of the supporting
      ligand. Using an appropriate ligand, isomerization of 1-alkenes to their Z-2
      isomers can be catalyzed in high yields using the cobalt(II) alkyl complexes as
      catalysts. Though an earlier paper attributed the regioselectivity and
      stereoselectivity to the preferred geometry of the BHE step, the results of
      isotope labeling experiments suggest that the selectivity may actually come from
      the alkene exchange step (again with spin acceleration). In general, the use of
      multiple intersecting spin states is envisioned as a profitable strategy for
      bringing about low reaction barriers and high selectivity in catalytic reactions.
      This effort requires high-accuracy computational models as well as ligand design
      that gives nearby spin states with appropriate geometries. 

PMID- 25989358
TI  - Heat inactivation of wine spoilage yeast Dekkera bruxellensis by hot water
      treatment.
AB  - Cell suspensions of four Dekkera bruxellensis strains (CBS 2499, CBS 2797, CBS
      4459 and CBS 4601) were subjected to heat treatment in deionized water at four
      different temperatures (55.0, 57.5, 60.0 and 62.5 degrees C) to investigate their
      thermal resistance. The decimal reduction times at a specific temperature were
      calculated from the resulting inactivation curves: the D-values at 55.0 degrees C
      ranged from 63 to 79.4 s, at 57.5 degrees C from 39.6 to 46.1 s, at 60.0 degrees
      C from 19.5 to 20.7 s, at 62.5 degrees C from 10.2 to 13.7 s. The z-values were
      between 9.2 and 10.2 degrees C, confirming that heat resistance is a strain
      dependent character. A protocol for the sanitization of 225 l casks by immersion
      in hot water was set up and applied to contaminated 3-year-old barrels. The heat
      penetration through the staves was evaluated for each investigated temperature by
      positioning a thermal probe at 8 mm deep. A treatment at 60 degrees C for an
      exposure time of 19 min allowed to eliminate the yeast populations up to a log
      count reduction of 8. SIGNIFICANCE AND IMPACT OF THE STUDY: Brettanomyces/Dekkera
      bruxellensis is the main yeast involved in red wine spoilage that occurs during
      ageing in barrel, generating considerable economic losses. Current sanitization
      protocols, performed using different chemicals, are ineffective due to the porous
      nature of the wood. The thermal inactivation of D. bruxellensis cells by hot
      water treatment proves to be efficacious and easy to perform, provided that the
      holding time at the killing temperature takes into account the filling time of
      the vessel and the time for the heat penetration into the wood structure.

PMID- 25989356
TI  - NADPH Oxidase-Derived Peroxynitrite Drives Inflammation in Mice and Human
      Nonalcoholic Steatohepatitis via TLR4-Lipid Raft Recruitment.
AB  - The molecular events that link NADPH oxidase activation and the induction of Toll
      like receptor (TLR)-4 recruitment into hepatic lipid rafts in nonalcoholic
      steatohepatitis (NASH) are unclear. We hypothesized that in liver, NADPH oxidase
      activation is key in TLR4 recruitment into lipid rafts, which in turn up
      regulates NF-kappaB translocation to the nucleus and subsequent DNA binding,
      leading to NASH progression. Results from confocal microscopy showed that liver
      from murine and human NASH had NADPH oxidase activation, which led to the
      formation of highly reactive peroxynitrite, as shown by 3-nitrotyrosine formation
      in diseased liver. Expression and recruitment of TLR4 into the lipid rafts were
      significantly greater in rodent and human NASH. The described phenomenon was
      NADPH oxidase, p47phox, and peroxynitrite dependent, as liver from p47phox
      deficient mice and from mice treated with a peroxynitrite decomposition catalyst
      [iron(III) tetrakis(p-sulfonatophenyl)porphyrin] or a peroxynitrite scavenger
      (phenylboronic acid) had markedly less Tlr4 recruitment into lipid rafts.
      Mechanistically, peroxynitrite-induced TLR4 recruitment was linked to increased
      IL-1beta, sinusoidal injury, and Kupffer cell activation while blocking
      peroxynitrite-attenuated NASH symptoms. The results strongly suggest that NADPH
      oxidase-mediated peroxynitrite drove TLR4 recruitment into hepatic lipid rafts
      and inflammation, whereas the in vivo use of the peroxynitrite scavenger
      phenylboronic acid, a novel synthetic molecule having high reactivity with
      peroxynitrite, attenuates inflammatory pathogenesis in NASH. 

PMID- 25989360
TI  - HLA-G*01:04~UTR3 Recipient Correlates With Lower Survival and Higher Frequency of
      Chronic Rejection After Lung Transplantation.
AB  - Lung transplantation (LTx) is a valid therapeutic option for selected patients
      with end-stage lung disease. Soluble HLA-G (sHLA-G) has been associated with
      increased graft survival and decreased rejection episodes in solid organ
      transplantation. HLA-G haplotypes named UTRs, defined by SNPs from both the 5'URR
      and 3'UTR, have been reported to reliably predict sHLA-G level. The aim of this
      retrospective study was to determine the impact of HLA-G alleles and UTR
      polymorphism from LTx recipients on anti-HLA allo-immunization risk, overall
      survival and chronic rejection (CLAD). HLA-G SNPs were genotyped in 124
      recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy
      individuals and 26 cystic fibrosis patients not requiring LTx. sHLA-G levels were
      measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA
      G*01:06~UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005)
      but not of long-term survival post-LTx. HLA-G*01:04~UTR3 haplotype was associated
      with lower levels of sHLA-G at D0 and M3 (p = 0.03), impaired long-term survival
      (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo
      donor-specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show
      the deleterious association of different HLA-G alleles and UTRs in LTx.

PMID- 25989359
TI  - Genetic loci that regulate ectopic calcification in response to knee trauma in
      LG/J by SM/J advanced intercross mice.
AB  - This study reports on genetic susceptibility to ectopic calcification in the LG/J
      and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships,
      destabilization of medial meniscus (DMM) was performed to induce joint injury. We
      found that joint destabilization instigated ectopic calcifications as detected
      and quantified by micro-CT. We performed quantitative trait locus (QTL) analysis
      to map ectopic calcification phenotypes to discrete genomic locations. To
      validate the functional significance of the selected QTL candidate genes, we
      compared mRNA expression between parental LG/J and SM/J inbred strains. Overall,
      we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with
      11 QTLs linked to synovial calcification. Functional and bioinformatic analyses
      of single nucleotide polymorphism (SNP) identified functional classifications
      relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone
      metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis
      (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and
      ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic
      calcification involves multiple mechanisms. Furthermore, the expression of 11 out
      of 78 candidate genes was significantly different between LG/J and SM/J.
      Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with
      synovial calcification. Taken together, our findings of multiple genetic loci
      suggest the involvement of multiple genes contributing to ectopic calcification.

PMID- 25989361
TI  - Life-threatening delayed hyperhemolytic transfusion reaction in a patient with
      sickle cell disease: effective treatment with eculizumab followed by rituximab.
AB  - BACKGROUND: Hyperhemolysis in sickle cell disease is a rare and potentially life
      threatening complication of transfusion. STUDY DESIGN AND METHODS: In this
      article we report a case of delayed hemolytic transfusion reaction with resultant
      hyperhemolysis triggered by an anti-IH autoantibody with alloantibody behavior.
      RESULTS: The anti-IH was reactive at room temperature as well as 37  degrees C,
      but only weakly reactive with autologous red blood cells. Initial cold agglutinin
      titer was 512. The profound, life-threatening, intravascular hemolysis was
      rapidly and dramatically reduced with the Complement 5 (C5) inhibitory antibody,
      eculizumab. The auto/allo cold agglutinin was subsequently suppressed with
      rituximab treatment. CONCLUSIONS: Eculizumab, a potent C5 inhibitory antibody,
      can be a rapid and effective therapy for hyperhemolytic transfusion reactions
      when given in a sufficient dose to fully block the activation of complement C5.

PMID- 25989362
TI  - The development of pediatric anesthesiology and critical care medicine at the
      Cincinnati Children's Hospital: an interview with Dr. Theodore Striker.
AB  - Dr. Theodore W. 'Ted' Striker (1936-), Professor of Anesthesiology and Pediatrics
      at the University of Cincinnati, has played a pioneering role in the development
      of pediatric anesthesiology in the United States. As a model educator, clinician,
      and administrator, he shaped the careers of hundreds of physicians-in-training
      and imbued them with his core values of honesty, integrity, and responsibility. 

PMID- 25989363
TI  - Acrylamide: inhibition of formation in processed food and mitigation of toxicity
      in cells, animals, and humans.
AB  - Potentially toxic acrylamide is largely derived from the heat-inducing reactions
      between the amino group of the amino acid asparagine and carbonyl groups of
      glucose and fructose in plant-derived foods including cereals, coffees, almonds,
      olives, potatoes, and sweet potatoes. This review surveys and consolidates the
      following dietary aspects of acrylamide: distribution in food, exposure and
      consumption by diverse populations, reduction of the content in different food
      categories, and mitigation of adverse in vivo effects. Methods to reduce
      acrylamide levels include selecting commercial food with a low acrylamide
      content, selecting cereal and potato varieties with low levels of asparagine and
      reducing sugars, selecting processing conditions that minimize acrylamide
      formation, adding food-compatible compounds and plant extracts to food
      formulations before processing that inhibit acrylamide formation during
      processing of cereal products, coffees, teas, olives, almonds, and potato
      products, and reducing multiorgan toxicity (antifertility, carcinogenicity,
      neurotoxicity, teratogenicity). The herein described observations and
      recommendations are of scientific interest for food chemistry, pharmacology, and
      toxicology, but also have the potential to benefit nutrition, food safety, and
      human health.

PMID- 25989364
TI  - Rhabdomyomatous mesenchymal hamartoma presenting as a sacral skin tag in two
      neonates with spinal dysraphism.
AB  - Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation
      involving the dermis and subcutaneous tissue, of which there were 62 reported
      cases through 2014. We report RMH in two neonates presenting as a sacral skin
      tag. In both cases, magnetic resonance imaging (MRI) of the spine showed evidence
      of spinal dysraphism, including a lipomyelomeningocele and a tethered cord.
      Surgical repair of the defects was performed. Histopathologic examination of the
      skin tags showed a haphazard arrangement of mature skeletal muscle fibers and
      adnexal elements, consistent with RMH. The second patient also had a hemangioma
      on the sacrum and was diagnosed with LUMBAR (lower body hemangioma and other
      cutaneous defects, urogenital anomalies/ulceration, myelopathy, bony deformities,
      anorectal/arterial anomalies, and renal anomalies) syndrome, an association
      between cutaneous infantile hemangiomas of the lower body and regional congenital
      anomalies. The apparent association of paraspinal RMH with spinal dysraphism
      suggests that aberrant migration of mesodermally derived tissues (including
      skeletal muscle fibers) during neural tube development may be responsible for the
      pathologic findings in the skin. Additional study of patients with spinal
      dysraphism and congenital cutaneous lesions may further support this hypothesis. 

PMID- 25989365
TI  - Exploring child dental service use among migrant families in metropolitan
      Melbourne, Australia.
AB  - BACKGROUND: This study describes and explores factors related to dental service
      use among migrant children. METHODS: A cross-sectional analysis of baseline data
      from Teeth Tales, an exploratory trial implementing a community based child oral
      health promotion intervention. The sample size and target population was 600
      families with 1-4 year old children from Iraqi, Lebanese and Pakistani
      backgrounds residing in metropolitan Melbourne. Participants were recruited into
      the study using purposive and snowball sampling techniques. RESULTS: Most (88%;
      550/625) children had never visited the dentist (mean (SD) age 3.06 years
      (1.11)). In the fully adjusted model the variable most significantly associated
      with child dental visiting was parent reported 'no reason for child to visit the
      dentist' (OR = 0.07, p < 0.001). Of those children whose parents reported their
      child had no reason to visit the dentist, 22% (37/165) experienced dental caries
      with 8% (13/165) at the level of cavitation. CONCLUSIONS: Dental service use by
      migrant preschool children was very low. The relationship between perceived
      dental need and dental service use is currently not aligned. One in 10 children
      of select migrant background had visited a dentist, which is in the context of 1
      in 3 with dental caries. To improve utilization, health services should consider
      organizational cultural competence, outreach and increased engagement with the
      migrant community.

PMID- 25989367
TI  - Social cognition is not associated with cognitive reserve in older adults.
AB  - Social and general cognitive abilities decline in late life. Those with high
      cognitive reserve display better general cognitive performance in old age;
      however, it is unknown whether this is also the case for social cognition. A
      total of 115 healthy older adults, aged 60-85 years (m = 44, f = 71) were
      assessed using The Awareness of Social Inference Test (TASIT-R; social
      cognition), the Lifetime of Experiences Questionnaire (LEQ; cognitive reserve),
      and the Wechsler Abbreviated Scale of Intelligence (WASI-II; general cognitive
      ability). The LEQ did not predict performance on any TASIT-R subtest: Emotion
      Evaluation Test (beta = -.097, p = .325), Social Inference - Minimal (beta = 
      .004, p = .972), or Social Inference - Enriched (beta = -.016, p = .878).
      Sensitivity analyses using two alternative cognitive reserve measures, years of
      education and the National Adult Reading Test, supported these effects. Cognitive
      reserve was strongly related to WASI-II performance. Unlike general cognitive
      ability, social cognition appears unaffected by cognitive reserve. Findings
      contribute to the emerging understanding that cognitive reserve differentially
      affects individual cognitive domains, which has implications for the theoretical
      understanding of cognitive reserve and its brain correlates. Cognitive measures
      unbiased by cognitive reserve may serve as best indicators of brain health, free
      of compensatory mechanisms.

PMID- 25989366
TI  - RpoS and quorum sensing control expression and polar localization of Vibrio
      cholerae chemotaxis cluster III proteins in vitro and in vivo.
AB  - The diarrheal pathogen Vibrio cholerae contains three gene clusters that encode
      chemotaxis-related proteins, but only cluster II appears to be required for
      chemotaxis. Here, we present the first characterization of V. cholerae's 'cluster
      III' chemotaxis system. We found that cluster III proteins assemble into foci at
      bacterial poles, like those formed by cluster II proteins, but the two systems
      assemble independently and do not colocalize. Cluster III proteins are expressed
      in vitro during stationary phase and in conjunction with growth arrest linked to
      carbon starvation. This expression, as well as expression in vivo in suckling
      rabbits, is dependent upon RpoS. V. cholerae's CAI-1 quorum sensing (QS) system
      is also required for cluster III expression in stationary phase and modulates its
      expression in vivo, but is not required for cluster III expression in response to
      carbon starvation. Surprisingly, even though the CAI-1 and AI-2 QS systems are
      thought to feed into the same signaling pathway, the AI-2 system inhibited
      cluster III gene expression, revealing that the outputs of the two QS systems are
      not always the same. The distinctions between genetic determinants of cluster III
      expression in vitro and in vivo highlight the distinctive nature of the in vivo
      environment. 

PMID- 25989368
TI  - Hydration, Orientation, and Conformation of Methylglyoxal at the Air-Water
      Interface.
AB  - Aqueous-phase processing of methylglyoxal (MG) has been suggested to constitute
      an important source of secondary organic aerosol (SOA). The uptake of MG to
      aqueous particles is higher than expected because its carbonyl moieties can
      hydrate to form geminal diols, as well as because MG and its hydration products
      can undergo aldol condensation reactions to form larger oligomers in solution. MG
      is known to be surface active, but an improved description of its surface
      behavior is crucial to understanding MG-SOA formation. These studies investigate
      MG adsorption, focusing on its hydration state at the air-water interface, using
      a combined experimental and theoretical approach that involves vibrational sum
      frequency spectroscopy, molecular dynamics simulations, and density functional
      theory calculations. Together, the experimental and theoretical data show that MG
      exists predominantly in a singly hydrated state (diol) at the interface, with a
      diol-tetrol ratio at the surface higher than that for the bulk. In addition to
      exhibiting a strong surface activity, we find that MG significantly perturbs the
      water structure at the interface. The results have implications for understanding
      the atmospheric fate of methylglyoxal. 

PMID- 25989369
TI  - Productivity links morphology, symbiont specificity and bleaching in the
      evolution of Caribbean octocoral symbioses.
AB  - Many cnidarians host endosymbiotic dinoflagellates from the genus Symbiodinium.
      It is generally assumed that the symbiosis is mutualistic, where the host
      benefits from symbiont photosynthesis while providing protection and
      photosynthetic substrates. Diverse assemblages of symbiotic gorgonian octocorals
      can be found in hard bottom communities throughout the Caribbean. While current
      research has focused on the phylo- and population genetics of gorgonian symbiont
      types and their photo-physiology, relatively less work has focused on
      biogeochemical benefits conferred to the host and how these benefits vary across
      host species. Here we examine this symbiosis among 11 gorgonian species collected
      in Bocas del Toro, Panama. By coupling light and dark bottle incubations (P/R)
      with (13)C-bicarbonate tracers, we quantified the link between holobiont oxygen
      metabolism with carbon assimilation and translocation from symbiont to host. Our
      data show that P/R varied among species, and was correlated with colony
      morphology and polyp size. Sea fans and sea plumes were net autotrophs (P/R>1.5),
      while nine species of sea rods were net heterotrophs with most below compensation
      (P/R<1.0). (13)C assimilation corroborated the P/R results, and maximum
      delta(13)Chost values were strongly correlated with polyp size, indicating higher
      productivity by colonies with high polyp SA:V. A survey of gorgonian-Symbiodinium
      associations revealed that productive species maintain specialized, obligate
      symbioses and are more resistant to coral bleaching, whereas generalist and
      facultative associations are common among sea rods that have higher bleaching
      sensitivities. Overall, productivity and polyp size had strong phylogenetic
      signals with carbon fixation and polyp size showing evidence of trait covariance.

PMID- 25989370
TI  - Local adaptation constrains the distribution potential of heat-tolerant
      Symbiodinium from the Persian/Arabian Gulf.
AB  - The symbiotic association of corals and unicellular algae of the genus
      Symbiodinium in the southern Persian/Arabian Gulf (PAG) display an exceptional
      heat tolerance, enduring summer peak temperatures of up to 36  degrees C. As yet,
      it is not clear whether this resilience is related to the presence of specific
      symbiont types that are exclusively found in this region. Therefore, we used
      molecular markers to identify the symbiotic algae of three Porites species along
      >1000 km of coastline in the PAG and the Gulf of Oman and found that a recently
      described species, Symbiodinium thermophilum, is integral to coral survival in
      the southern PAG, the world's hottest sea. Despite the geographic isolation of
      the PAG, we discovered that representatives of the S. thermophilum group can also
      be found in the adjacent Gulf of Oman providing a potential source of
      thermotolerant symbionts that might facilitate the adaptation of Indian Ocean
      populations to the higher water temperatures expected for the future. However,
      corals from the PAG associated with S. thermophilum show strong local adaptation
      not only to high temperatures but also to the exceptionally high salinity of
      their habitat. We show that their superior heat tolerance can be lost when these
      corals are exposed to reduced salinity levels common for oceanic environments
      elsewhere. Consequently, the salinity prevailing in most reefs outside the PAG
      might represent a distribution barrier for extreme temperature-tolerant
      coral/Symbiodinium associations from the PAG. 

PMID- 25989371
TI  - Long-term soil transplant simulating climate change with latitude significantly
      alters microbial temporal turnover.
AB  - To understand soil microbial community stability and temporal turnover in
      response to climate change, a long-term soil transplant experiment was conducted
      in three agricultural experiment stations over large transects from a warm
      temperate zone (Fengqiu station in central China) to a subtropical zone (Yingtan
      station in southern China) and a cold temperate zone (Hailun station in northern
      China). Annual soil samples were collected from these three stations from 2005 to
      2011, and microbial communities were analyzed by sequencing microbial 16S
      ribosomal RNA gene amplicons using Illumina MiSeq technology. Our results
      revealed a distinctly differential pattern of microbial communities in both
      northward and southward transplantations, along with an increase in microbial
      richness with climate cooling and a corresponding decrease with climate warming.
      The microbial succession rate was estimated by the slope (w value) of linear
      regression of a log-transformed microbial community similarity with time (time
      decay relationship). Compared with the low turnover rate of microbial communities
      in situ (w=0.046, P<0.001), the succession rate at the community level was
      significantly higher in the northward transplant (w=0.058, P<0.001) and highest
      in the southward transplant (w=0.094, P<0.001). Climate warming lead to a faster
      succession rate of microbial communities as well as lower species richness and
      compositional changes compared with in situ and climate cooling, which may be
      related to the high metabolic rates and intense competition under higher
      temperature. This study provides new insights into the impacts of climate change
      on the fundamental temporal scaling of soil microbial communities and microbial
      phylogenetic biodiversity. 

PMID- 25989372
TI  - Molecular mechanisms underlying the close association between soil Burkholderia
      and fungi.
AB  - Bacterial species belonging to the genus Burkholderia have been repeatedly
      reported to be associated with fungi but the extent and specificity of these
      associations in soils remain undetermined. To assess whether associations between
      Burkholderia and fungi are widespread in soils, we performed a co-occurrence
      analysis in an intercontinental soil sample collection. This revealed that
      Burkholderia significantly co-occurred with a wide range of fungi. To analyse the
      molecular basis of the interaction, we selected two model fungi frequently co
      occurring with Burkholderia, Alternaria alternata and Fusarium solani, and
      analysed the proteome changes caused by cultivation with either fungus in the
      widespread soil inhabitant B. glathei, whose genome we sequenced. Co-cultivation
      with both fungi led to very similar changes in the B. glathei proteome. Our
      results indicate that B. glathei significantly benefits from the interaction,
      which is exemplified by a lower abundance of several starvation factors that were
      highly expressed in pure culture. However, co-cultivation also gave rise to
      stress factors, as indicated by the increased expression of multidrug efflux
      pumps and proteins involved in oxidative stress response. Our data suggest that
      the ability of Burkholderia to establish a close association with fungi mainly
      lies in the capacities to utilize fungal-secreted metabolites and to overcome
      fungal defense mechanisms. This work indicates that beneficial interactions with
      fungi might contribute to the survival strategy of Burkholderia species in
      environments with sub-optimal conditions, including acidic soils. 

PMID- 25989374
TI  - MRSA spa t1081, a highly transmissible strain endemic to Hong Kong, China, in the
      Netherlands.

PMID- 25989373
TI  - Cross-depth analysis of marine bacterial networks suggests downward propagation
      of temporal changes.
AB  - Interactions among microbes and stratification across depths are both believed to
      be important drivers of microbial communities, though little is known about how
      microbial associations differ between and across depths. We have monitored the
      free-living microbial community at the San Pedro Ocean Time-series station,
      monthly, for a decade, at five different depths: 5 m, the deep chlorophyll
      maximum layer, 150 m, 500 m and 890 m (just above the sea floor). Here, we
      introduce microbial association networks that combine data from multiple ocean
      depths to investigate both within- and between-depth relationships, sometimes
      time-lagged, among microbes and environmental parameters. The euphotic zone, deep
      chlorophyll maximum and 890 m depth each contain two negatively correlated
      'modules' (groups of many inter-correlated bacteria and environmental conditions)
      suggesting regular transitions between two contrasting environmental states. Two
      thirds of pairwise correlations of bacterial taxa between depths lagged such that
      changes in the abundance of deeper organisms followed changes in shallower
      organisms. Taken in conjunction with previous observations of seasonality at 890
      m, these trends suggest that planktonic microbial communities throughout the
      water column are linked to environmental conditions and/or microbial communities
      in overlying waters. Poorly understood groups including Marine Group A,
      Nitrospina and AEGEAN-169 clades contained taxa that showed diverse association
      patterns, suggesting these groups contain multiple ecological species, each
      shaped by different factors, which we have started to delineate. These
      observations build upon previous work at this location, lending further credence
      to the hypothesis that sinking particles and vertically migrating animals
      transport materials that significantly shape the time-varying patterns of
      microbial community composition.

PMID- 25989375
TI  - Genetic diversity and recombination within bufaviruses: Detection of a novel
      strain in Hungarian bats.
AB  - Bats are important hosts of many viruses and in several cases they may serve as
      natural reservoirs even for viruses with zoonotic potential worldwide, including
      Europe. However, they also serve as natural reservoir for other virus groups with
      important evolutionary relevance and yet unknown zoonotic potential. We performed
      viral metagenomic analyses on Miniopterus schreibersii bat fecal samples. As a
      result, a novel parvovirus was detected for the first time in European bats.
      Although, bufavirus was recently discovered as a novel human infecting
      parvovirus, here we report sequence data of the first bufavirus from European
      bats related to human bufaviruses. Based on our sequence data a possible
      intragenic recombination event was detected within bufaviruses which may serves
      as an important milestone in their evolution. 

PMID- 25989376
TI  - Impact of HBV genotypes A and D genetic variability on infection evolution.
AB  - HBV is characterized by a high genetic variability, which is the basis of its
      classification into eight genotypes (A-H). HBV infection is associated with
      different outcomes, from self-limiting acute hepatitis to active chronic
      hepatitis, asymptomatic carriage, and occult infection. The aim of this study was
      to analyze the genetic variability of HBV genotypes A and D isolates from 79
      cases of self-limiting acute hepatitis and chronic hepatitis, in order to
      identify HBV variants associated with resolution or chronicity of acute HBV
      infection. The entire preS-S sequence and a fragment of 346 bp of the preC-C
      region, containing Enhancer II and Basal Core Promoter sequences, were analyzed.
      A phylogenetic analysis of preS/S region showed that the 45.45% (15/33) of
      isolates from acute hepatitis cases were genotype A compared to 8.69% (4/46) of
      chronic hepatitis cases. (p = 0.0002). Mutations associated with immune-escape
      (T131N, D144A/E, G145K), amino acid polymorphisms in "a determinant" domain of S
      protein and mutations/deletions in preC/C region were found in isolates from
      acute and chronic hepatitis B cases. In this study mutations/deletions in preS-S
      and preC-C regions, usually associated with fulminant acute hepatitis, advanced
      forms of liver disease and increased risk for HCC, were identified in HBV strains
      of genotype A and D obtained both from patients with self-limiting acute HBV
      infection and from persistent infected patients. This founding probably is due to
      the natural viral evolution under host immune response and to the circulation of
      a wide variety of HBV strains in our geographic area because of the ancient
      introduction of genotype D and the migrant fluxes from North Africa. Moreover,
      the analysis of circulation of new HBV antigenic variants is fundamental for the
      epidemiological surveys and for the evaluation of the impact of viral evolution
      on vaccine prophylaxis strategies.

PMID- 25989377
TI  - Aggregation-Prone Amyloid-beta?Cu(II) Species Formed on the Millisecond Timescale
      under Mildly Acidic Conditions.
AB  - Metal ions and their interaction with the amyloid beta (Abeta) peptide might be
      key elements in the development of Alzheimer's disease. In this work the effect
      of Cu(II) on the aggregation of Abeta is explored on a timescale from
      milliseconds to days, both at physiological pH and under mildly acidic
      conditions, by using stopped-flow kinetic measurements (fluorescence and light
      scattering), (1) H NMR relaxation and ThT fluorescence. A minimal reaction model
      that relates the initial Cu(II) binding and Abeta folding with downstream
      aggregation is presented. We demonstrate that a highly aggregation prone
      Abeta?Cu(II) species is formed on the sub-second timescale at mildly acidic pH.
      This observation might be central to the molecular origin of the known
      detrimental effect of acidosis in Alzheimer's disease. 

PMID- 25989378
TI  - Malignant hyperthermia, a Scandinavian update.
AB  - BACKGROUND: Malignant Hyperthermia (MH) is a rare pharmacogenetic disorder,
      triggered by halogenated anesthetics and/or succinylcholine. In susceptible
      individuals, these drugs can activate an explosive life threatening clinical
      reaction. Leading symptoms are hypercarbia, muscle rigidity, and metabolic
      acidosis. MH is inherited in an autosomal-dominant manner and linked to mutations
      in the large ryanodine 1 gene (RYR1) gene in the majority of cases. Very few MH
      patients have been found to carry mutations in the CACNA1S gene. METHODS: For
      this review a large litterature search was carried out and the Swedish MH
      database consisting of 436 probands who have undergone in vitro muscle
      contraction test (IVCT) during 1984-2014 was analyzed. RESULTS: Twelve different
      MH causative mutations have been found in Swedish patients so far. These
      mutations lead to a disturbed calcium balance in striated muscle tissue. A muscle
      biopsy for the IVCT or finding of an approved causative mutation are required for
      the diagnosis. CONCLUSION: A Malignant Hyperthermia susceptible (MHS) patient
      should be anesthetized with trigger-free anesthesia. There are a few reports of
      MH-like reactions in patients unrelated to anesthesia. The outcome is dependent
      on early recognizing of the reaction and fast disconnection of the trigger agents
      and administration of dantrolene.

PMID- 25989380
TI  - Interventions for cough in cancer.
AB  - BACKGROUND: This is an updated version of the original Cochrane review first
      published in Issue 9, 2010 on "Interventions for cough in cancer". Cough is a
      common symptom in patients with malignancies, especially in patients with lung
      cancer. Cough is not well controlled in clinical practice and clinicians have few
      management options to treat it. OBJECTIVES: The primary objective was to
      determine the effectiveness of interventions, both pharmacological and non
      pharmacological, (other than chemotherapy and external beam radiotherapy) in the
      management of cough in malignant disease (especially in lung cancer). SEARCH
      METHODS: For this update, we searched for relevant studies in CENTRAL and DARE
      (The Cochrane Library); MEDLINE; EMBASE; PsycINFO; AMED and CINAHL to 9 June
      2014. In addition, we searched for ongoing trials via the metaRegister of
      controlled trials (mRCT), ClinicalTrials.gov, the World Health Organization (WHO)
      International Clinical Trials Registry Platform (ICTRP) and the UK Clinical
      Research Network Study Portfolio. SELECTION CRITERIA: We selected randomised
      controlled trials (RCTs) and clinical trials (quasi-experimental trials and
      trials where there is a comparison group but no mention of randomisation) in
      participants with primary or metastatic lung cancer or other cancers. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed the titles and
      abstracts of all studies for inclusion, and extracted data from all included
      studies independently before reaching consensus. A third review author arbitrated
      on any disagreement. Meta-analysis was not attempted due to the heterogeneity of
      the studies. MAIN RESULTS: For the original version of the review, 17 studies met
      the inclusion criteria and examined either brachytherapy, laser or photodynamic
      therapy (eight studies) or a variety of pharmacological therapies (nine studies).
      Overall, there was an absence of credible evidence and the majority of studies
      were of low methodological quality and at high risk of bias. Brachytherapy in a
      variety of doses seemed to improve cough in selected participants, suggesting
      that possibly the lowest effective dose should be used to minimise side effects.
      Photodynamic therapy was examined in one study and, while improvements in cough
      were observed, its role in relationship to other therapies for cough was unclear.
      Some indication of positive effect was observed with morphine, codeine,
      dihydrocodeine, levodropropizine, sodium cromoglycate and butamirate citrate
      linctus (cough syrup), although all studies had significant risk of bias. For
      this update, we did not identify any additional trials for inclusion. Two ongoing
      trials were identified but no study results were available. AUTHORS' CONCLUSIONS:
      No new trials were included since the publication of the original version of this
      review, while 11 new studies that were identified were eventually excluded from
      this review. Therefore, our conclusions remain unchanged. No practice
      recommendations could be drawn from this review. There is an urgent need to
      increase the number and quality of studies evaluating the effects of
      interventions for the management of cough in cancer.

PMID- 25989379
TI  - Naturally occurring tolerance acquisition to foods in previously allergic
      children is characterized by antigen specificity and associated with increased
      subsets of regulatory T cells.
AB  - BACKGROUND: Food allergy affects approximately 6-8% of children, and increasing
      in prevalence. Some children naturally outgrow their food allergy without
      intervention, but the mechanisms by which this occurs remain poorly understood.
      We sought to investigate the role of regulatory T cells in the development of
      naturally acquired tolerance. METHODS: Fifty-eight children (1-18 years) with
      either egg or peanut allergy, recent acquisition of natural tolerance to egg or
      peanut, or no food allergy were studied. Peripheral blood mononuclear cells
      (PBMC) from these groups were stimulated with relevant antigen for 48 h and flow
      cytometry performed to characterize both surface (CD3, CD4, CD25, CD14, CD19, and
      CD127) and intracellular markers (IL-10, Foxp3, and IL-5). RESULTS: Resting PBMC
      from naturally tolerant patients had significantly increased
      CD3+CD4+CD25+CD127loFoxp3+ cells, when compared to allergic or control patients
      (mean 6.36 vs. 2.37 vs. 2.62%, respectively, P < 0.05). Upon stimulation with
      relevant antigen, naturally tolerant patients also had increased IL-10-expressing
      CD25+CD127lo cells (6.33 vs. 1.65 vs. 0.7, P < 0.01), Foxp3+ cells (mean 12.6 vs.
      5.42 vs. 3%, P < 0.01), and CD4+ cells (mean 4.48 vs. 1.59 vs. 0.87%, P < 0.01);
      the increase was not observed in PBMCs from allergic or control patients.
      Additionally, this upregulation was only seen with relevant antigen stimulation
      and not upon stimulation with unrelated antigen. CONCLUSION: The increased
      CD3+CD4+CD25+CD127lo cells at baseline and upon stimulation and increased
      induction of IL-10-producing cells of several types, including Tr1 cells, from
      naturally tolerant patients suggests an important role for regulatory T cell
      subsets in the acquisition of natural tolerance.

PMID- 25989381
TI  - Evaluation of the effectiveness of a silver-impregnated medical cap for topical
      treatment of nipple fissure of breastfeeding mothers.
AB  - OBJECTIVE: This study evaluated the effectiveness of a medical topical treatment
      device named Silver Cap((r)) (Depofarma S.P.A., Mogliano Veneto, Treviso, Italy)
      for the treatment of nipple fissure in lactating women and its local
      tolerability, compared with the standard of care for nipple fissure treatment
      during breastfeeding. SUBJECTS AND METHODS: From December 2013 to September 2014,
      we recruited 40 women for symptomatic nipple fissures during lactation.
      Participants were randomized into two groups: the Silver Cap group (20 women;
      group A) or the control group (20 women; Group B, standard of breastfeeding
      care). All participants received breastfeeding education provided by a board
      certified lactation consultant. Group A was instructed to use the Silver Cap.
      Group B had a handbook with the standard of care for nipple treatment after each
      breastfeeding. Both groups received a questionnaire for a daily assessment. The
      duration of both treatments was 15 days. We performed a clinical evaluation on
      Days 0 and 2 and a follow-up by telephone on Day 7, and all participants
      underwent final evaluation face to face on Day 15. We performed photographic
      recording of the nipple on Day 0 and Day 15. RESULTS: There were no statistical
      differences in follow-up between the two treatments at Day 2. There was a
      significant and a more rapid resolution of painful symptoms in the Silver Cap
      group compared with the control group (p<0.05) at Days 7 and 15. Treatment with
      Silver Cap was more appreciated by the participants than standard care (p<0.05).
      Four participants in the Silver Cap group and six in the control group dropped
      out of the study. No local or systemic reactions were reported following Silver
      Cap application. CONCLUSIONS: Results of treatment with Silver Cap were more
      effective than standard care of nipple fissure treatment in term of resolution of
      painful symptoms. It promoted the healing process of lesions, and it was well
      tolerated and accepted by participants.

PMID- 25989382
TI  - An Immunohistochemical Study of Matrix Components in Early-Stage Vascular Canals
      Within Mandibular Condylar Cartilage in Midterm Human Fetuses.
AB  - Matrix components of vascular canals (VCs) in human fetal mandibular condylar
      cartilage (15-16 weeks of gestation) were analyzed by immunohistochemistry.
      Prevascular canals (PVCs), consisting of spindle-shaped cells without capillary
      invasion, were observed within the cartilage. Intense immunoreactivity for
      collagen type I, weak immunoreactivity for aggrecan and tenascin-C, weak
      hyaluronan (HA) staining, and abundant argyrophilic fibers in PVCs indicated that
      they contain noncartilaginous fibrous connective tissues that was different from
      those in the perichondrium/periosteum. These structural and immunohistochemical
      features of PVCs are different from those of previously reported cartilage canals
      of the long bone. Capillaries entered the VCs from the periosteum and ascended
      through VCs. Following capillary invasion, loose connective tissue had formed in
      the lower part of VCs, and immunoreactivity for collagen types I and III,
      tenascin-C, and HA staining was evident in the matrix of loose connective tissue.
      No chondroclasts or osteogenic cells were seen at the front of capillary
      invasion, although small, mononuclear tartrate-resistant acid phosphatase (TRAP)
      positive cells were present. Meanwhile, TRAP-positive, multinucleated
      chondroclasts and flattened, osteoblast-like cells were observed in the loose
      connective tissue at the lower part of VCs. These results may indicate slow
      progress of endochondral ossification in human fetal mandibular condyle. Further,
      unique matrix components in PVCs/VCs, which were different from those in
      cartilage canals in long bone, may reflect the difference of speed of
      endochondral ossification in cartilage canals and human fetal mandibular
      condyles.

PMID- 25989384
TI  - MicroRNA-873 Inhibits Morphine-Induced Macrophage Apoptosis by Elevating A20
      Expression.
AB  - OBJECTIVES: To study the role of microRNA-873 (miR-873) in suppressing morphine
      induced macrophage apoptosis and morphine dependence, and to identify molecular
      targets within the miR-873 pathway for the treatment of immune suppression and
      morphine addiction. METHODS: As morphine elevates TLR9 expression and induces
      TLR9-mediated apoptosis, we used TLR9 knockout Balb/C mice to study TLR9
      independent effects of miR-873 on morphine-induced macrophage apoptosis. Forty
      TLR9-knockout mice were randomly and equally assigned to morphine group and
      control group. Following the administration of morphine, miR-873 mimics or miR
      negative control was injected into mice in each group. Using freshly isolated
      macrophages from mice and RAW264.7 murine macrophage cell line, miR-873 level was
      determined by qRT-PCR and morphine induced apoptosis was measured by TUNEL
      assays. Western blotting was used to detect and quantify the expression level of
      A20, a protein that negatively regulates inflammation and TNF-induced apoptosis.
      RESULTS: qRT-PCR analysis revealed a markedly lower expression of miR-873 in
      freshly isolated peritoneal macrophages, liver tissue and spleen tissue in the
      morphine group compared with the corresponding tissues in the control group.
      TUNEL assays showed that the apoptosis rates in the morphine groups treated with
      miR-873 mimics was markedly lower than their respective control groups. Western
      blotting results showed that A20 expression level was sharply elevated in the
      experimental groups treated with miR-873 mimics than the negative and blank
      control groups. CONCLUSIONS: Our results show that miR-873 elevates A20 levels
      and inhibits morphine-induced macrophage apoptosis.

PMID- 25989383
TI  - Agonist- and antagonist-induced up-regulation of surface 5-HT3 A receptors.
AB  - BACKGROUND AND PURPOSE: The 5-HT3 receptor is a member of the pentameric ligand
      gated ion channel family and is pharmacologically targeted to treat irritable
      bowel syndrome and nausea/emesis. Furthermore, many antidepressants elevate
      extracellular concentrations of 5-HT. This study investigates the functional
      consequences of exposure of recombinant 5-HT3 A receptors to agonists and
      antagonists. EXPERIMENTAL APPROACH: We used HEK cells stably expressing
      recombinant 5-HT3 A receptors and the ND7/23 (mouse neuroblastoma/dorsal root
      ganglion hybrid) cell line, which expresses endogenous 5-HT3 receptors. Surface
      expression of recombinant 5-HT3 A receptors, modified to contain the bungarotoxin
      (BTX) binding sequence, was quantified using fluorescence microscopy to image BTX
      conjugated fluorophores. Whole cell voltage-clamp electrophysiology was used to
      measure the density of current mediated by 5-HT3 A receptors. KEY RESULTS: 5-HT3
      A receptors were up-regulated by the prolonged presence of agonists (5-HT and m
      chlorophenylbiguanide) and antagonists (MDL-72222 and morphine). The up
      regulation of 5-HT3 A receptors by 5-HT and MDL-72222 was time- and concentration
      dependent but was independent of newly translated receptors. The phenomenon was
      observed for recombinant rodent and human 5-HT3 A receptors and for endogenous 5
      HT3 receptors in neuronal ND7/23 cells. CONCLUSIONS AND IMPLICATIONS: Up
      regulation of 5-HT3 A receptors, following exposure to either agonists or
      antagonists suggests that this phenomenon may occur in response to different
      therapeutic agents. Medications that elevate 5-HT levels, such as the
      antidepressant inhibitors of 5-HT reuptake and antiemetic inhibitors of 5-HT3
      receptor function, may both raise receptor expression. However, this will require
      further investigation in vivo.

PMID- 25989385
TI  - Polymorphisms in the canine glucocorticoid receptor alpha gene (NR3C1alpha).
AB  - Corticosteroids are one of the most extensively used class of therapeutic agents
      in dogs. In human patients, response to corticosteroid therapy has been
      correlated with the presence of certain polymorphisms of the glucocorticoid
      receptor gene (NR3C1). Depending on the polymorphism present, patients may show
      either increased sensitivity to glucocorticoid-induced adverse effects or
      resistance to their therapeutic effects. Because response to corticosteroid
      therapy in dogs can also be variable and unpredictable, we hypothesized that
      genetic variability exists in the canine NR3C1 gene. The aim of this study was to
      sequence the coding regions of the canine NR3C1 gene in a representative sample
      of dogs. Samples from 97 dogs from four previously identified genetic groupings
      of domestic breeds (Asian/Ancient, Herding, Hunting, and Mastiff) were sequenced
      and evaluated. Four exons contained polymorphisms and four exons showed no
      variation from the reference sequence. A total of six single nucleotide
      polymorphisms (SNPs) were identified including four synonymous SNPs and two
      nonsynonymous SNPs (c.811A>T and c.2111T>C). No dogs were homozygous for either
      variant allele, while 23 dogs were heterozygous for the c.811A>T allele and 2
      were heterozygous for c.2111T>C allele. The amino acid changes caused by c.811A>T
      (serine to cysteine) and c.2111T>C (isoleucine to threonine) were both predicted
      by in silico analysis to be 'probably damaging' to structure and function of the
      resulting protein. We conclude that NR3C1 polymorphisms occur in dogs and may
      cause individual variation in response to corticosteroid therapy. 

PMID- 25989386
TI  - Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis
      Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical
      Therapy.
AB  - BACKGROUND & AIMS: Patients with cirrhosis and variceal hemorrhage have a high
      risk of rebleeding. We performed a prospective randomized trial to compare the
      prevention of rebleeding in patients given a small-diameter covered stent vs
      those given hepatic venous pressure gradient (HVPG)-based medical therapy
      prophylaxis. METHODS: We performed an open-label study of patients with cirrhosis
      (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany.
      Patients were assigned randomly more than 5 days after variceal hemorrhage to
      groups given a small covered transjugular intrahepatic portosystemic stent-shunt
      (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and
      isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were
      assigned to groups (baseline) and 2 weeks later. In the medical group, patients
      with an adequate reduction in HVPG (responders) remained on the drugs whereas
      nonresponders underwent only variceal band ligation. The study was closed 10
      months after the last patient was assigned to a group. The primary end point was
      variceal rebleeding. Survival, safety (adverse events), and quality of life
      (based on the Short Form-36 health survey) were secondary outcome measures.
      RESULTS: A significantly smaller proportion of patients in the TIPS group had
      rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A
      slightly higher proportion of patients in the TIPS group experienced adverse
      events, including encephalopathy (18% vs 8% for medical treatment; P = .05).
      Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before
      hemodynamic control was possible. Per-protocol analysis showed that rebleeding
      occurred in a smaller proportion of the 32 responders (18%) than in nonresponders
      who received variceal band ligation (31%) (P = .06). Fifteen patients from the
      medical group (16%) underwent TIPS placement during follow-up evaluation, mainly
      for refractory ascites. Survival time and quality of life did not differ between
      both randomized groups. CONCLUSIONS: Placement of a small-diameter, covered TIPS
      was straightforward and prevented variceal rebleeding in patients with Child A or
      B cirrhosis more effectively than drugs, which often required step-by-step
      therapy. However, TIPS did not increase survival time or quality of life and
      produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

PMID- 25989387
TI  - A Digital Reference Object to Analyze Calculation Accuracy of PET Standardized
      Uptake Value.
AB  - PURPOSE: To determine the extent of variations in computing standardized uptake
      value (SUV) by body weight (SUV(BW)) among different software packages and to
      propose a Digital Imaging and Communications in Medicine (DICOM) reference test
      object to ensure the standardization of SUV computation between medical image
      viewing workstations. MATERIALS AND METHODS: Research ethics board approval was
      not necessary because this study only evaluated images of a phantom. A synthetic
      set of positron emission tomographic (PET)/computed tomographic (CT) image data,
      called a digital reference object (DRO), with known SUV was created. The DRO was
      sent to 16 sites and evaluated on 21 different PET/CT display software packages.
      Users were asked to draw various regions of interest (ROIs) on specific features
      and report the maximum, minimum, mean, and standard deviation of the SUVs for
      each ROI. Numerical tolerances were defined for each metric, and the fraction of
      reported values within the tolerance was recorded, as was the mean, standard
      deviation, and range of the metrics. RESULTS: The errors in reported maximum SUV
      ranged from -37.8% to 0% for an isolated voxel with 4.11:1 target-to-background
      activity level, and errors in the reported mean SUV ranged from -1.6% to 100% for
      a region with controlled noise. There was also a range of errors in the less
      commonly used metrics of minimum SUV and standard deviation SUV. CONCLUSION: The
      variability of computed SUV(BW) between different software packages is
      substantial enough to warrant the introduction of a reference standard for
      medical image viewing workstations.

PMID- 25989388
TI  - PALM-IST: Pathway Assembly from Literature Mining--an Information Search Tool.
AB  - Manual curation of biomedical literature has become extremely tedious process due
      to its exponential growth in recent years. To extract meaningful information from
      such large and unstructured text, newer and more efficient mining tool is
      required. Here, we introduce PALM-IST, a computational platform that not only
      allows users to explore biomedical abstracts using keyword based text mining but
      also extracts biological entity (e.g., gene/protein, drug, disease, biological
      processes, cellular component, etc.) information from the extracted text and
      subsequently mines various databases to provide their comprehensive inter
      relation (e.g., interaction, expression, etc.). PALM-IST constructs protein
      interaction network and pathway information data relevant to the text search
      using multiple data mining tools and assembles them to create a meta-interaction
      network. It also analyzes scientific collaboration by extraction and creation of
      "co-authorship network," for a given search context. Hence, this useful
      combination of literature and data mining provided in PALM-IST can be used to
      extract novel protein-protein interaction (PPI), to generate meta-pathways and
      further to identify key crosstalk and bottleneck proteins. PALM-IST is available
      at www.hpppi.iicb.res.in/ctm. 

PMID- 25989392
TI  - Toward Rare Blood Cell Preservation for RNA Sequencing.
AB  - Cancer is driven by various events leading to cell differentiation and disease
      progression. Molecular tools are powerful approaches for describing how and why
      these events occur. With the growing field of next-generation DNA sequencing,
      there is an increasing need for high-quality nucleic acids derived from human
      cells and tissues-a prerequisite for successful cell profiling. Although advances
      in RNA preservation have been made, some of the largest biobanks still do not
      employ RNA blood preservation as standard because of limitations in low blood
      input volume and RNA stability over the whole gene body. Therefore, we have
      developed a robust protocol for blood preservation and long-term storage while
      maintaining RNA integrity. Furthermore, we explored the possibility of using the
      protocol for preserving rare cell samples, such as circulating tumor cells. The
      results of our study confirmed that gene expression was not impacted by the
      preservation procedure (r(2) > 0.88) or by long-term storage (r(2) = 0.95), with
      RNA integrity number values averaging over 8. Similarly, cell surface antigens
      were still available for antibody selection (r(2) = 0.95). Lastly, data mining
      for fusion events showed that it was possible to detect rare tumor cells among a
      background of other cells present in blood irrespective of fixation. Thus, the
      developed protocol would be suitable for rare blood cell preservation followed by
      RNA sequencing analysis. 

PMID- 25989393
TI  - Autoimmune hepatitis: Diagnosis and treatment guide in Japan, 2013.

PMID- 25989394
TI  - Gender-Specific Differences in Skeletal Muscle 11beta-HSD1 Expression Across
      Healthy Aging.
AB  - CONTEXT: Cushing's syndrome is characterized by marked changes in body
      composition (sarcopenia, obesity, and osteoporosis) that have similarities with
      those seen in aging. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      converts glucocorticoids to their active form (cortisone to cortisol in humans),
      resulting in local tissue amplification of effect. OBJECTIVE: To evaluate 11beta
      HSD1 expression and activity with age, specifically in muscle. To determine
      putative causes for increased activity with age and its consequences upon
      phenotypic markers of adverse aging. DESIGN: Cross-sectional observational study.
      SETTING: National Institute for Health Research-Wellcome Trust Clinical Research
      Facility, Birmingham, United Kingdom. PATIENTS OR OTHER PARTICIPANTS: Healthy
      human volunteers age 20 to 81 years (n = 134; 77 women, 57 men). INTERVENTIONS:
      Day attendance at research facility for baseline observations, body composition
      analysis by dual-energy x-ray absorptiometry, jump-plate mechanography, grip
      strength analysis, baseline biochemical profiling, urine collection, and vastus
      lateralis muscle biopsy. MAIN OUTCOME MEASURE(S): Skeletal muscle gene
      expression, urine steroid profile, bivariate correlations between
      expression/activity and phenotypic/biochemical variables. RESULTS: Skeletal
      muscle 11beta-HSD1 expression was increased 2.72-fold in women over 60 years of
      age compared to those aged 20-40 years; no differences were observed in men.
      There was a significant positive correlation between skeletal muscle 11beta-HSD1
      expression and age in women across the group (rho = 0.40; P = .009). No
      differences in expression of 11beta-HSD type 2, glucocorticoid receptor, or
      hexose-6-phosphate dehydrogenase between age groups were observed in either sex.
      Urinary steroid markers of 11beta-HSD1, 11beta-HSD type 2, or 5alpha-reductase
      were similar between age groups. Skeletal muscle 11beta-HSD1 expression was
      associated with reduced grip strength in both sexes and correlated positively
      with percentage of body fat, homeostasis model of assessment for insulin
      resistance, total cholesterol, LH, and FSH and negatively with bone mineral
      content and IGF-1 in women. CONCLUSIONS: Skeletal muscle 11beta-HSD1 is up
      regulated with age in women and is associated with reduced grip strength, insulin
      resistance, and an adverse body composition profile. Selective inhibition of
      11beta-HSD1 may offer a novel strategy to prevent and/or reverse age-related
      sarcopenia.

PMID- 25989395
TI  - Hand allotransplantation: operating room set-up and team coordination.
AB  - Vascularized composite allotransplantion requires careful planning and precise
      execution. The Director of the Hand Transplant Program must coordinate many
      personnel including nurses, anesthesiologists, transplant coordinators, surgeons,
      support staff, and hospital administrators. The operation is performed only after
      surgical rehearsal has reinforced the specialized role of each of these team
      members and the workflow of equipment and personnel has been optimized. 

PMID- 25989396
TI  - PBNR: Percutaneous Blunt Needle Reduction of Bony Mallet Injuries.
AB  - Mallet finger injuries are common; treatment goals include achieving joint
      stability, preventing extensor lag, and subsequent swan-neck deformity. We
      describe a simple technique for improving intraoperative bony mallet reduction,
      which may avoid the requirement for closed Ishiguro extension blocking wires or
      open fixation, and present a prospective case series (n=12). Intraoperative
      percutaneous blunt needle reduction (PBNR) is achieved under image intensifier
      guidance. Using artery forceps, a blunt fill needle tip is manipulated onto the
      proximal avulsed fragment; this is then guided into a reduced position and
      maintained using a well-formed Zimmer splint across the distal interphalangeal
      joint in 15- to 30-degree extension. There were 5 injuries involving >1/3 of the
      articular surface (Doyle's classification IVb) and 7 injuries involving >1/2 of
      the articular surface (Doyle's classification IVc). Mean hand therapy follow-up
      was 10.6+/-1.0 weeks, extensor lag was 4.6+/-1.7 degrees, and all patients
      achieved full functional recovery with return to normal daily activity. No
      complications were reported. Closed techniques, for example, Ishiguro extension
      blocking wires, may reduce the risks associated with open reduction, but do not
      avoid further articular surface damage. PBNR offers the surgeon a useful adjunct
      to the treatment options for bony mallet injuries, without excluding progression
      to surgical fixation if required. PBNR represents a less-invasive management
      option for bony mallet injures where surgical fixation may also be indicated. 

PMID- 25989397
TI  - Recognition and fixation of crista supinatoris fractures in Monteggia injuries.
AB  - In Monteggia fracture dislocations of the elbow, the lateral collateral ligament
      complex is disrupted as the radial head dislocates from the capitellum. A
      persistently incompetent lateral ulnar collateral ligament (LUCL) predisposes to
      posterolateral rotary instability of the elbow, thus restoration of the LUCL is
      essential for recovery. Although LUCL disruptions following elbow dislocations
      typically occur at the lateral humeral origin, we have identified a series of
      Monteggia injuries where the LUCL is avulsed from its ulnar insertion along with
      a fracture fragment containing the crista supinatoris. Failure to recognize and
      appropriately treat the crista supinatoris fracture in this injury may result in
      LUCL incompetence and risk symptomatic instability. The following technique
      describes the recognition and surgical treatment of Monteggia injuries,
      specifically recognizing the crista supinatoris fracture. Using this technique,
      patients reliably experience good functional outcomes with normal elbow
      stability. 

PMID- 25989399
TI  - Evolving conceptualisations of validity: impact on the process and outcome of
      assessment.

PMID- 25989400
TI  - The trouble with validity: what is part of it and what is not?

PMID- 25989401
TI  - Manipulating practice variables to maximise learning.

PMID- 25989402
TI  - Self-regulated learning: the challenge of learning in clinical settings.

PMID- 25989403
TI  - When I say ... learning culture.

PMID- 25989404
TI  - When I say ... mastery learning.

PMID- 25989405
TI  - A contemporary approach to validity arguments: a practical guide to Kane's
      framework.
AB  - CONTEXT: Assessment is central to medical education and the validation of
      assessments is vital to their use. Earlier validity frameworks suffer from a
      multiplicity of types of validity or failure to prioritise among sources of
      validity evidence. Kane's framework addresses both concerns by emphasising key
      inferences as the assessment progresses from a single observation to a final
      decision. Evidence evaluating these inferences is planned and presented as a
      validity argument. OBJECTIVES: We aim to offer a practical introduction to the
      key concepts of Kane's framework that educators will find accessible and
      applicable to a wide range of assessment tools and activities. RESULTS: All
      assessments are ultimately intended to facilitate a defensible decision about the
      person being assessed. Validation is the process of collecting and interpreting
      evidence to support that decision. Rigorous validation involves articulating the
      claims and assumptions associated with the proposed decision (the
      interpretation/use argument), empirically testing these assumptions, and
      organising evidence into a coherent validity argument. Kane identifies four
      inferences in the validity argument: Scoring (translating an observation into one
      or more scores); Generalisation (using the score[s] as a reflection of
      performance in a test setting); Extrapolation (using the score[s] as a reflection
      of real-world performance), and Implications (applying the score[s] to inform a
      decision or action). Evidence should be collected to support each of these
      inferences and should focus on the most questionable assumptions in the chain of
      inference. Key assumptions (and needed evidence) vary depending on the
      assessment's intended use or associated decision. Kane's framework applies to
      quantitative and qualitative assessments, and to individual tests and programmes
      of assessment. CONCLUSIONS: Validation focuses on evaluating the key claims,
      assumptions and inferences that link assessment scores with their intended
      interpretations and uses. The Implications and associated decisions are the most
      important inferences in the validity argument.

PMID- 25989406
TI  - Operationalising elaboration theory for simulation instruction design: a Delphi
      study.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility of incorporating
      the Delphi process within the simplifying conditions method (SCM) described in
      elaboration theory (ET) to identify conditions impacting the complexity of
      procedural skills for novice learners. METHODS: We generated an initial list of
      conditions impacting the complexity of lumbar puncture (LP) from key informant
      interviews (n = 5) and a literature review. Eighteen clinician-educators from six
      different medical specialties were subsequently recruited as expert panellists.
      Over three Delphi rounds, these panellists rated: (i) their agreement with the
      inclusion of the simple version of the conditions in a representative ('epitome')
      training scenario, and (ii) how much the inverse (complex) version increases LP
      complexity for a novice. Cronbach's alpha-values were used to assess inter-rater
      agreement. RESULTS: All panellists completed Rounds 1 and 2 of the survey and 17
      completed Round 3. In Round 1, Cronbach's alpha-values were 0.89 and 0.94 for
      conditions that simplify and increase LP complexity, respectively; both values
      increased to 0.98 in Rounds 2 and 3. With the exception of 'high CSF (cerebral
      spinal fluid) pressure', panellists agreed with the inclusion of all conditions
      in the simplest (epitome) training scenario. Panellists rated patient movement,
      spinal anatomy, patient cooperativeness, body habitus, and the presence or
      absence of an experienced assistant as having the greatest impact on the
      complexity of LP. CONCLUSIONS: This study demonstrated the feasibility of using
      expert consensus to establish conditions impacting the complexity of procedural
      skills, and the benefits of incorporating the Delphi method into the SCM. These
      data can be used to develop and sequence simulation scenarios in a progressively
      challenging manner. If the theorised learning gains associated with ET are
      realised, the methods described in this study may be applied to the design of
      simulation training for other procedural and non-procedural skills, thereby
      advancing the agenda of theoretically based instruction design in health care
      simulation.

PMID- 25989407
TI  - Exploring the factors influencing clinical students' self-regulated learning.
AB  - OBJECTIVES: The importance of self-regulated learning (SRL) has been broadly
      recognised by medical education institutions and regulatory bodies. Supporting
      the development of SRL skills has proven difficult because self-regulation is a
      complex interactive process and we know relatively little about the factors
      influencing this process in real practice settings. The aim of our study was
      therefore to identify factors that support or hamper medical students' SRL in a
      clinical context. METHODS: We conducted a constructivist grounded theory study
      using semi-structured interviews with 17 medical students from two universities
      enrolled in clerkships. Participants were purposively sampled to ensure variety
      in age, gender, experience and current clerkship. The Day Reconstruction Method
      was used to help participants remember their activities of the previous day. The
      interviews were transcribed verbatim and analysed iteratively using constant
      comparison and open, axial and interpretive coding. RESULTS: Self-regulated
      learning by students in the clinical environment was influenced by the specific
      goals perceived by students, the autonomy they experienced, the learning
      opportunities they were given or created themselves, and the anticipated outcomes
      of an activity. All of these factors were affected by personal, contextual and
      social attributes. CONCLUSIONS: Self-regulated learning of medical students in
      the clinical environment is different for every individual. The factors
      influencing this process are affected by personal, social and contextual
      attributes. Some of these are similar to those known from previous research in
      classroom settings, but others are unique to the clinical environment and include
      the facilities available, the role of patients, and social relationships
      pertaining to peers and other hospital staff. To better support students' SRL, we
      believe it is important to increase students' metacognitive awareness and to
      offer students more tailored learning opportunities.

PMID- 25989408
TI  - Nationwide study of publication misrepresentation in applicants to residency.
AB  - OBJECTIVES: This study was conducted to assess the prevalence of research
      publication misrepresentation amongst Canadian Resident Matching Service (CaRMS)
      applicants to a single surgical subspecialty residency as a potential means of
      assessing professional behaviour. METHODS: The authors reviewed CaRMS application
      forms to Canadian otolaryngology residency programmes over a 3-year period (2006
      2008) for peer-reviewed publications reported as 'published', 'accepted' and 'in
      press'. Citations were verified by searching PubMed, Google Scholar and
      electronic journals. Misrepresentation was defined as any of: (i) falsely claimed
      authorship of an existing article; (ii) claimed authorship of a non-existing
      article, and (iii) improper ordering of authorship. Outcomes included descriptive
      statistics, as well as sub-analyses pertaining to age, gender, affiliated medical
      school and academic degree, and number of publications per applicant. RESULTS: A
      total of 427 peer-reviewed publications were reported by 124 of 182 applicants
      (68% of applicants reported at least one publication). Of the 385 verifiable
      publications, 47 (12% of articles) were misrepresented by 29 applicants (23% of
      applicants claiming publication) self-reporting at least one publication. Age,
      gender, location of medical training, prior academic degree and number of
      citations per applicant did not relate to likelihood of misrepresentation (p >
      0.05). CONCLUSIONS: This study documents the nationwide prevalence of publication
      misrepresentation amongst applicants to Canadian otolaryngology residency
      programmes. The high rate of misrepresentation aligns with data reported in the
      literature and highlights the need to institute measures to dissuade graduates
      from this form of unprofessional behaviour.

PMID- 25989409
TI  - 'Stereotypes are reality': addressing stereotyping in Canadian Aboriginal medical
      education.
AB  - CONTEXT: Efforts are underway in many parts of the world to develop medical
      education curricula that address the health care issues of indigenous
      populations. The topic of stereotypes and their impact on such peoples' health,
      however, has received little attention. An examination of stereotypes will shed
      light on dominant cultural attitudes toward Aboriginal people that can affect
      quality of care and health outcomes in Aboriginal patients. OBJECTIVES: This
      study examines the views of undergraduate medical students regarding Canadian
      Aboriginal stereotypes and how they potentially affect Aboriginal people's
      health. The goal of this study was to gain insight into how medical learners
      perceive issues related to racism, discrimination and social stereotypes and to
      draw attention to gaps in Aboriginal health curricula. METHODS: This study
      involved a convenience sample of medical learners drawn from one undergraduate
      medical programme in western Canada. Using a semi-structured interview guide, we
      conducted a total of seven focus group interviews with 38 first- and second-year
      undergraduate medical students. Data were analysed using a thematic content
      analysis approach. RESULTS: Medical students recognise that stereotypes are
      closely related to processes of racism and discrimination. However, they
      generally feel that stereotypes of Aboriginal people are rooted in reality.
      Students also identified medical school as one of the environments in which they
      are commonly exposed to negative views of Aboriginal people. Student responses
      suggest they see the cultural gap between Aboriginal and non-Aboriginal people as
      being both a cause and a consequence of discrimination against Aboriginal people.
      CONCLUSIONS: The results of this study suggest that teaching medical students
      about the realities and impacts of stereotypes on Aboriginal peoples is a good
      starting point from which to address issues of racism and health inequities
      affecting the health of Aboriginal people.

PMID- 25989410
TI  - Medical electives in sub-Saharan Africa: a host perspective.
AB  - CONTEXT: Electives are part of most Western medical school curricula. It is
      estimated that each year 3000-4000 undergraduate medical students from the UK
      alone undertake an elective in a developing country. The impact of these
      electives has given some cause for concern, but the views of elective hosts are
      largely missing from the debate. OBJECTIVES: The purpose of this study was to
      evaluate the organisation, outcomes and impacts of medical electives in sub
      Saharan Africa from a host perspective. METHODS: A qualitative analysis of 14
      semi-structured interviews with elective hosts at seven elective sites in Malawi,
      Zambia and Tanzania was carried out. A framework analysis approach was used to
      analyse 483 minutes of audio-recorded data. RESULTS: Hosts were committed to
      providing elective experiences but their reasons for doing so varied
      considerably, in particular between urban or teaching hospitals and rural or
      mission hospitals. Nurturing a group of professionals who will understand the
      provision of health care from a global perspective was the main reason reported
      for hosting an elective, along with generating potential future staff. Hosts
      argued that the quality of supervision should be judged according to local
      context. Typical concerns cited in the literature with reference to clinical
      activities, safety and ethics did not emerge as issues for these hosts. However,
      in under-resourced clinical contexts, the training of local students sometimes
      had to take priority. Electives could be improved with greater student
      preparation and some contribution from sending institutions to support teaching,
      supervision or patient care. CONCLUSIONS: The challenge to both students and
      their sending institutions is to progress towards giving something proportionate
      back in return for the learning experiences received. There is clearly room to
      improve electives from the hosts' perspective, but individually host institutions
      lack the opportunity or ability to achieve change.

PMID- 25989411
TI  - Costs and inconsistencies in US IRB review of low-risk medical education
      research.
AB  - CONTEXT: Advances in communication technologies over the last two decades have
      transformed the way medical education research is conducted, creating
      opportunities for multi-institution national and international studies. Although
      these studies enable researchers to gain broader understandings of educational
      processes across institutions, they increase the need for multiple institutional
      review board (IRB) reviews to ensure the protection of human subjects.
      OBJECTIVES: This study describes the process of obtaining multiple IRB approvals
      of the same protocol for a multi-site, low-risk, medical education research
      project in the USA. The burden of obtaining those reviews and their consistency
      are assessed. The associated time and costs, and implications for the research
      process are detailed. METHODS: Following review by the investigators' parent
      institution IRB, the project team circulated a uniform protocol for conduct of a
      low-risk, medical education survey to the IRBs of 89 US medical schools for
      review. The processes and time required to obtain approvals were recorded to
      estimate associated research team personnel costs. RESULTS: Approval could not be
      obtained from five IRBs as a result of insurmountable procedural barriers. A
      total of 67 IRBs eventually deferred to the parent IRB determination. The
      remaining IRBs required a variety of additional procedural processes before
      ultimately agreeing with the original determination. The personnel costs
      associated with obtaining the 84 approvals amounted to US$121,344. CONCLUSIONS:
      Considering the value of multi-site designs to address a range of research
      questions, enhance participant diversity and develop representative findings,
      solutions must be found to counter inefficiencies of current IRB review processes
      for low-risk research, such as that usually conducted in medical education.
      Although we acknowledge that local review is an essential protective measure for
      research involving identifiable communities that are uniquely susceptible to
      social or economic harm, this report suggests that proposals to modernise and
      streamline IRB review processes for low-risk research are timely and relevant.

PMID- 25989412
TI  - Selection and study performance.

PMID- 25989413
TI  - Underlying factors in medical school admissions.

PMID- 25989415
TI  - Comparison of air-agitated liquid-liquid microextraction and ultrasound-assisted
      emulsification microextraction for polycyclic aromatic hydrocarbons determination
      in hookah water.
AB  - In this work, two disperser-free microextraction methods, namely, air-agitated
      liquid-liquid microextraction and ultrasound-assisted emulsification
      microextraction are compared for the determination of a number of polycyclic
      aromatic hydrocarbons in aqueous samples, followed by gas chromatography with
      flame ionization detection. The effects of various experimental parameters upon
      the extraction efficiencies of both methods are investigated. Under the optimal
      conditions, the enrichment factors and limits of detection were found to be in
      the ranges of 327-773 and 0.015-0.05 ng/mL for air-agitated liquid-liquid
      microextraction and 406-670 and 0.015-0.05 ng/mL for ultrasound-assisted
      emulsification microextraction, respectively. The linear dynamic ranges and
      extraction recoveries were obtained to be in the range of 0.05-120 ng/mL (R(2) >=
      0.995) and 33-77% for air-agitated liquid-liquid microextraction and 0.05-110
      ng/mL (R(2) >= 0.994) and 41-67% for ultrasound-assisted emulsification
      microextraction, respectively. To investigate this common view among some people
      that smoking hookah is healthy due to the passage of smoke through the hookah
      water, samples of both the hookah water and hookah smoke were analyzed. 

PMID- 25989414
TI  - 15-year incidence of diabetic ketoacidosis at onset of type 1 diabetes in
      children from a regional setting (Auckland, New Zealand).
AB  - We assessed the incidence of diabetic ketoacidosis (DKA) in children aged <15
      years with newly diagnosed type 1 diabetes mellitus (T1DM) in the Auckland Region
      (New Zealand) in 1999-2013, in a retrospective review of a complete regional
      cohort. DKA and its severity were classified according to ISPAD 2014 guidelines.
      Of 730 children presenting with new-onset T1DM over the 15-year time period, 195
      cases had DKA of any severity (27%). There was no change in the incidence of DKA
      or the proportion of children with severe DKA at presentation. The incidence of
      DKA among children aged <2.0 years (n = 40) was 53% compared to 25% for those
      aged 2-14 years (n = 690; p = 0.005). In children aged 2-14 years, increasing age
      at diagnosis was associated with greater likelihood of DKA at presentation (p =
      0.025), with the odds of DKA increasing 1.06 times with each year increase in
      age. Non-Europeans were more likely to present in DKA than New Zealand Europeans
      (OR 1.52; p = 0.048). Despite a consistent secular trend of increasing incidence
      of T1DM, there was no reduction in the incidence of DKA in new-onset T1DM in the
      Auckland Region over time. Thus, it is important to explore ways to reduce DKA
      risk. 

PMID- 25989416
TI  - Contrasting age related changes in autism spectrum disorder phenomenology in
      Cornelia de Lange, Fragile X, and Cri du Chat syndromes: Results from a 2.5 year
      follow-up.
AB  - Little is known about the way in which the characteristics of autism spectrum
      disorder (ASD) develop and manifest across the age span in individuals with
      genetic syndromes. In this study we present findings from a two and a half year
      follow-up of the characteristics associated with ASD in three syndromes: Cornelia
      de Lange (CdLS), Fragile X (FXS), and Cri du Chat (CdCS). Parents and carers of
      251 individuals (CdLS=67, CdCS=42, and FXS=142) completed the Social
      Communication Questionnaire (SCQ) at Time 1 (T1) and again two and a half years
      later (T2). The FXS and CdLS groups were more likely to meet the cut-offs for
      both autism and ASD and show greater severity of ASD related behaviors, at both
      T1 and T2, compared to the CdCS group. Older individuals (>15yrs) with CdLS were
      more likely to meet the cut off for ASD than younger individuals (<=15 yrs) with
      the syndrome and more likely to show greater severity of social impairments. In
      FXS repetitive behaviors were found to become less prominent with age and in CdCS
      social impairments were reported to be more severe with age. There were no
      significant changes between T1 and T2 in the severity of ASD characteristics in
      the CdCS and CdLS groups. The FXS group showed significantly fewer repetitive
      behaviors and less severe impairments in social interaction over this time frame.
      The findings suggest that while there may be similarities in overall severity and
      presentation of ASD characteristics in CdLS and FXS, these characteristics have
      divergent patterns of development within these groups.

PMID- 25989417
TI  - Metaproteomics reveals major microbial players and their biodegradation functions
      in a large-scale aerobic composting plant.
AB  - Composting is an appropriate management alternative for municipal solid waste;
      however, our knowledge about the microbial regulation of this process is still
      scare. We employed metaproteomics to elucidate the main biodegradation pathways
      in municipal solid waste composting system across the main phases in a large
      scale composting plant. The investigation of microbial succession revealed that
      Bacillales, Actinobacteria and Saccharomyces increased significantly with respect
      to abundance in composting process. The key microbiologic population for
      cellulose degradation in different composting stages was different. Fungi were
      found to be the main producers of cellulase in earlier phase. However, the
      cellulolytic fungal communities were gradually replaced by a purely bacterial one
      in active phase, which did not support the concept that the thermophilic fungi
      are active through the thermophilic phase. The effective decomposition of
      cellulose required the synergy between bacteria and fungi in the curing phase. 

PMID- 25989418
TI  - A truncated C-terminal fragment of Mycobacterium tuberculosis HSP70 enhances cell
      mediated immune response and longevity of the total IgG to influenza A virus M2e
      protein in mice.
AB  - As the importance of virus-specific IgG2a and strong induction of Th1 type immune
      response for virus clearance was reported, conventional influenza vaccines induce
      a highly humoral immune response and fail to induce cytotoxic T-lymphocyte (CTL)
      immunity. Hence, in agreement with heat shock protein 70 (HSP70) acting as Th1
      cytokine-like adjuvant, an Escherichia coli-expressed r4M2e.HSP70c fusion protein
      comprising C-terminus of Mycobacterium tuberculosis HSP70 genetically fused to
      four tandem repeats of influenza A virus M2e was constructed. Then, the case
      control study was carried out to evaluate the humoral and cellular responses
      elicited against M2e in Balb/C mice by intramuscular immunization with
      r4M2e.HSP70c alone. Our results showed that r4M2e.HSP70c rather than control
      groups, r4M2e, r4M2e+Alum, or rHSP70c, significantly elevated both longevity and
      serum level of the total M2e-specific IgG antibody, induced a Th1 skewed humoral
      and cellular immune responses, increased the level of IFN-gamma in BALF, and
      promoted the proliferation of peripheral blood lymphocytes. Furthermore, a virus
      challenge experiment revealed that mice vaccinated with r4M2e.HSP70c limited the
      severity of influenza A disease by 100% survival rate, less sever body weight
      loss and delaying the onset of morbidity in mice for 2days rather than other
      control groups. Here, we used r4M2e.HSP70c to stimulate M2e-specific antibody and
      cellular immune responses in Balb/C mice. The mHSP70c in the fusion form induced
      a long lasting Th1 skewed humoral and cellular immune responses against its
      associated protein. It seems anti-M2e antibodies limit viral replication and
      ameliorate influenza infection that allows the immune system to induce
      sterilizing HA-antibody against whole virion that leads to full protection
      against virulent influenza infection. 

PMID- 25989420
TI  - Coccidioides exposure and coccidioidomycosis among prison employees, California,
      United States.
AB  - Responding to a request by corrections agency management, we investigated
      coccidioidomycosis in prison employees in central California, a
      coccidioidomycosis-endemic area. We identified 103 cases of coccidioidomycosis
      that occurred over 4.5 years. As a result, we recommended training and other
      steps to reduce dust exposure among employees and thus potential exposure to
      Coccidioides. 

PMID- 25989419
TI  - Medicaid Expansions and Crowd-Out: Evidence from HIFA Premium Assistance
      Programs.
AB  - OBJECTIVE: To evaluate the effect of the Oregon and New Mexico Health Insurance
      Flexibility and Accountability (HIFA) demonstrations. HIFA is an optional state
      Medicaid expansion targeted at adults and children with incomes below 200 percent
      of the federal poverty level (FPL). The study has five research questions: What
      type of health insurance do HIFA enrollees self report in surveys? What are the
      demographic characteristics of these enrollees? What type of health insurance
      coverage, if any, did HIFA enrollees have just prior to enrollment in the HIFA
      program? Among those with prior coverage, what prompted participation in the HIFA
      program? What type of health insurance, if any, would HIFA enrollees have in the
      absence of HIFA? METHODS: Data were collected via telephone interviews with a
      total of 406 enrollees from Oregon and 409 enrollees from New Mexico. The survey
      was conducted between July 7 and September 20, 2009, for both states. The sample
      frame for the survey was based on administrative records of adults enrolled in
      June 2009. After completion of the survey, active enrollment status as of the
      date the telephone interview was confirmed. Respondents no longer enrolled at the
      time of the survey (7 cases in NM and 14 in OR) were excluded from the analysis.
      The final sample size was 794 verified HIFA enrollees. RESULTS: HIFA enrollees
      tended to be middle-aged, male, and relatively unhealthy. Employment status
      varied tremendously from the self-employed to retired to unable to work. HIFA
      enrollees were reasonably well educated with 80 percent having at least a high
      school education. Most HIFA enrollees (90 percent) reported being uninsured just
      prior to participation in HIFA. Of those who were uninsured, most reported having
      been uninsured for an extended time-a year or more. Most enrollees joined HIFA
      because they lacked access to health insurance or could not afford insurance on
      the private market. The overwhelming majority (76 percent) of respondents
      believed that they would be uninsured in the absence of HIFA, with few
      considering either an employer plan or private purchase to be a viable option.
      Over 90 percent of enrollees correctly indicated they had insurance coverage.
      However, characterization of the type of coverage was problematic, particularly
      in the absence of the program-specific name. CONCLUSIONS: HIFA enrolled a
      relatively sick, male, middle-aged population that tended to have been long-term
      uninsured--the kind of enrollees for which the programs were designed--with
      little apparent crowd-out of private insurance. The reported health status
      coupled with low incomes suggests that individual purchase is unlikely, a
      sentiment echoed by the respondents. In the absence of HIFA, most enrollees
      believed they would rejoin the ranks of the uninsured from where they came.

PMID- 25989421
TI  - Temporal trends of perfluoroalkyl substances (PFAS) in eggs of coastal and
      offshore birds: Increasing PFAS levels associated with offshore bird species
      breeding on the Pacific coast of Canada and wintering near Asia.
AB  - Perfluoroalkyl substances (PFAS) such as perfluoroalkyl carboxylates (PFCAs) and
      perfluoroalkyl sulfonates (PFSAs) have become virtually ubiquitous throughout the
      environment, and, based on laboratory studies, have known toxicological
      consequences. Various national and international voluntary phase-outs and
      restrictions on these compounds have been implemented over the last 10 to 15
      years. In the present study, we examine trends (1990/1991-2010/2011) in aquatic
      birds (ancient murrelet, Synthliboramphus antiquus [2009 only]; Leach's storm
      petrels, Oceanodroma leucorhoa; rhinoceros auklets, Cerorhinca monocerata; double
      crested cormorants, Phalacrocorax auritus; and great blue herons, Ardea
      herodias). The PFCA, PFSA, and stable isotope (delta(15) N and delta(13) C) data
      collected from these species from the Pacific coast of Canada, ranging over 20 to
      30 years, were used to investigate temporal changes in PFAS coupled to dietary
      changes. Perfluorooctane sulfonic acid (PFOS), the dominant PFSA compound in all
      4 species, increased and subsequently decreased in auklet and cormorant eggs in
      line with the manufacturing phase-out of PFOS and perfluorooctanoic acid (PFOA),
      but concentrations continuously increased in petrel eggs and remained largely
      unchanged in heron eggs. Dominant PFCA compounds varied between the offshore and
      coastal species, with increases seen in the offshore species and little or
      variable changes seen in the coastal species. Little temporal change was seen in
      stable isotope values, indicating that diet alone is not driving observed PFAS
      concentrations.

PMID- 25989422
TI  - Enhanced Boosting of Oral Absorption of Lopinavir Through Electrospray
      Coencapsulation with Ritonavir.
AB  - In vivo activities of absorption enhancers coencapsulated with poorly absorptive
      drugs in the same enteric-coated particles were evaluated. Lopinavir [a substrate
      of cytochrome P450 3A (CYP3A)] and ritonavir (an inhibitor of CYP3A-mediatd
      metabolism) were used as a model drug and a model absorption enhancer,
      respectively. Lopinavir and ritonavir were encapsulated into enteric-coated
      particles as amorphous forms using coaxial electrospray deposition. The
      electrospray treatment resulted in dramatic improvement of dissolution profiles
      of both compounds, probably because of complete amorphization and superior
      dispersion efficiency of the particles. Poor absorption of lopinavir in rats was
      observed after oral administration of enteric-coated particles containing
      lopinavir alone. When the particles were coadministered with enteric-coated
      particles containing ritonavir alone, lopinavir absorption was boosted. The
      boosting effect was further enhanced when ritonavir was coencapsulated with
      lopinavir into the same enteric-coated particles. A significant increase in area
      under the plasma concentration-time curve reflected an extension of mean
      residence time rather than an elevation of Cmax . Lopinavir absorption was
      improved presumably because lopinavir was always accompanied by a practical
      amount of ritonavir required for the boosting during the gastrointestinal transit
      of the particles. Not only did the electrospray coencapsulation technique improve
      drug absorption, but also increased trough concentration that might result in the
      reduction of the number of doses.

PMID- 25989423
TI  - Impact of HMG-CoA reductase inhibitors on the incidence of polyomavirus
      associated nephropathy in renal transplant recipients with human BK polyomavirus
      viremia.
AB  - BACKGROUND: Up to 20% of renal transplant recipients (RTR) will develop human BK
      polyomavirus (BKPyV) viremia. BKPyV viremia is a pre-requisite of polyomavirus
      associated nephropathy (PyVAN). Risk of BKPyV infections increases with
      immunosuppression. Currently, the only effective therapy against PyVAN is
      reductions in immunosuppression, but this may increase the risk of rejection. In
      vitro data have shown that pravastatin dramatically decreased caveolin-1
      expression in human renal proximal tubular epithelial cells (HRPTEC) and
      suppressed BKPyV infection in these cells. Based on these data, we postulated
      that statin therapy may prevent the progression of BKPyV viremia to PyVAN.
      PATIENTS AND METHODS: A multicenter, retrospective study was conducted in adult
      RTR transplanted between July 2005 and March 2012. All patients with documented
      BKPyV viremia (viral load >500 copies/mL on 2 consecutive tests) were included.
      Group I consisted of patients taking a statin before the BKPyV viremia diagnosis
      (n = 32), and Group II had no statin exposure before or after the BKPyV viremia
      diagnosis (n = 36). The primary endpoint was the incidence of PyVAN. RESULTS:
      Demographic data, transplant characteristics, and the degree of immunosuppression
      (i.e., induction/maintenance therapies, rejection treatment) were similar between
      the groups, with the exception of more diabetics in Group I. The incidence of
      PyVAN was comparable between the 2 groups (Group I = 28.1% vs. Group II = 41.7%;
      P = 0.312). CONCLUSIONS: Despite the proven in vitro effectiveness of pravastatin
      preventing BKPyV infection in HRPTEC, statins at doses maximized for cholesterol
      lowering, in RTR with BKPyV viremia, did not prevent progression to PyVAN.

PMID- 25989424
TI  - Synthesis, G-quadruplexes DNA binding, and photocytotoxicity of novel cationic
      expanded porphyrins.
AB  - Intensive reports allowed the conclusion that molecules with extended aromatic
      surfaces always do good jobs in the DNA interactions. Inspired by the previous
      successful researches, herein, we designed a series of cationic porphyrins with
      expanded planar substituents, and evaluated their binding behaviors to G
      quadruplex DNA using the combination of surface-enhanced raman, circular
      dichroism, absorption spectroscopy and fluorescence resonance energy transfer
      melting assays. Asymmetrical tetracationic porphyrin with one phenyl-4-N-methyl-4
      pyridyl group and three N-methyl-4-pyridyl groups exhibit the best G4-DNA binding
      affinities among all the designed compounds, suggesting that the bulk of the
      substituents should be matched to the width of the grooves they putatively lie
      in. Theoretical calculations applying the density functional theory have been
      carried out and explain the binding properties of these porphyrins reasonably.
      Meanwhile, these porphyrins were proved to be potential photochemotherapeutic
      agents since they have photocytotoxic activities against both myeloma cell
      (Ag8.653) and gliomas cell (U251) lines. 

PMID- 25989425
TI  - Mycotic Pseudoaneurysms of the Coronary Arteries.
AB  - BACKGROUND: Mycotic coronary artery aneurysms are rare and are often fatal
      without early recognition and prompt surgical management. METHODS: We present a
      case of mycotic pseudoaneurysm of the left main coronary artery (LMCA) after
      disseminated methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. A
      review of the literature in regards to the surgical management of coronary artery
      mycotic pseudoaneurysms was conducted. RESULTS: There were 26 reported cases of
      surgical management of coronary artery mycotic pseudoaneurysms. Coronary artery
      bypass surgery (CABG) and excision was the most common management (73.1% of cases
      reviewed). CONCLUSION: This case highlights the difficultly in diagnosing mycotic
      coronary artery pseudoaneurysms.

PMID- 25989426
TI  - The Effect of the Mediterranean Diet on Serum Total Antioxidant Capacity in Obese
      Patients: A Randomized Controlled Trial.
AB  - OBJECTIVE: The aim of this work was to evaluate the combined effect of physical
      activity and 1 and 12 months' adherence to Mediterranean diet (MD) on serum total
      antioxidant capacity (TAC) in obese patients, as well as factors contributing to
      TAC. METHODS: One hundred twenty-four patients were randomly assigned to either
      MD combined with physical activity or standard hypolypemic diet (SHD) with
      physical activity. Both groups received counseling and education during the
      initial week and were invited for the follow-up visits, where data on body weight
      and blood samples were collected. TAC was determined by Trolox equivalent
      antioxidant capacity and urate was determined using a uricase spectrophotometric
      method at the initial visit and after 1 and 12 months. RESULTS: Eighty-four
      patients finished the 12-month program and were analyzed. The baseline and 1- and
      12-month mean (+/-SD) TAC values in the MD group (n = 40) were 2.38 +/- 0.48,
      2.51 +/- 0.47, and 2.47 +/- 0.45 mmol Trolox equivalent (TE)/L, respectively. In
      the SHD group (n = 44), TAC values were 2.37 +/- 0.49, 2.48 +/- 0.49, and 2.31 +/
      0.51 mmol TE/L, respectively. There was a statistically significant main effect
      for time (p < 0.001), as well as statistically significant time-diet interaction
      effect (p = 0.009). There was no statistically significant correlation between
      TAC and uric acid after 1 month (p = 0.733) or 12 months (p = 0.844) of the
      intervention. Based on the regression model, which included gender, diet,
      physical activity level, and percentage body weight change, the type of diet was
      the only significantly contributing factor to TAC change after the 12-month
      period, F = 3.867, df = 3, p = 0.012, R = 0.358, R(2) = 0.128. CONCLUSION: This
      randomized controlled trial with diet and physical activity intervention and TAC
      as a primary outcome demonstrated initial antioxidant improvement in both MD and
      SHD groups and a long-term beneficial effect of MD. The results imply that diet
      composition-olive oil, nuts, and fish in particular-combined with physical
      activity modify antioxidant capacity.

PMID- 25989428
TI  - Racial and ethnic differences in physician assistant salaries.
AB  - Two recent reports using different data sets concluded that female physician
      assistants (PAs) earn substantially less than male PAs. Similar data comparing
      the effect of race and ethnicity on salary have not been compiled. This article
      examines the possibility of racial and ethnic salary disparities in PA salaries
      using data from the 2009 survey of members of the American Academy of Physician
      Assistants. 

PMID- 25989427
TI  - Coat Protein-Dependent Behavior of Poly(ethylene glycol) Tails in Iron Oxide Core
      Virus-like Nanoparticles.
AB  - Here we explore the formation of virus-like nanoparticles (VNPs) utilizing 22-24
      nm iron oxide nanoparticles (NPs) as cores and proteins derived from viral
      capsids of brome mosaic virus (BMV) or hepatitis B virus (HBV) as shells. To
      accomplish that, hydrophobic FeO/Fe3O4 NPs prepared by thermal decomposition of
      iron oleate were coated with poly(maleic acid-alt-octadecene) modified with
      poly(ethylene glycol) (PEG) tails of different lengths and grafting densities.
      MRI studies show high r2/r1 relaxivity ratios of these NPs that are practically
      independent of the polymer coating type. The versatility and flexibility of the
      viral capsid protein are on display as they readily form shells that exceed their
      native size. The location of the long PEG tails upon shell formation was
      investigated by electron microscopy and small-angle X-ray scattering. PEG tails
      were located differently in the BMV and HBV VNPs, with the BMV VNPs
      preferentially entrapping the tails in the interior and the HBV VNPs allowing the
      tails to extend through the capsid, which highlights the differences between
      intersubunit interactions in these two icosahedral viruses. The robustness of the
      assembly reaction and the protruding PEG tails, potentially useful in modulating
      the immune response, make the systems introduced here a promising platform for
      biomedical applications. 

PMID- 25989429
TI  - Pharmacologic management of chronic stable angina.
AB  - Chronic stable angina is a significant problem in older adults. The goal of
      therapy is to provide symptomatic relief, improve patient quality of life, and
      prevent subsequent angina or myocardial infarction that could lead to sudden
      death. The efficacy and safety of drugs such as beta-blockers and calcium channel
      blockers for managing chronic stable angina in older adults has not been
      rigorously investigated. Drug selection should be based on physiologic
      alterations, patient comorbidities, adverse reaction profile, and cost. 

PMID- 25989430
TI  - A permanent reminder of a lesson in empathy.

PMID- 25989432
TI  - Should patients with chronic liver disease receive venous thromboembolism
      prophylaxis?
AB  - Chronic liver disease has long been considered the prime example of acquired
      bleeding disorders due to its associated coagulopathies, namely elevated
      international normalized ratio (INR) and thrombocytopenia. Recent evidence has
      shown that patients with chronic liver disease also are at risk for hospital
      acquired venous thromboembolism (VTE). The safety and efficacy of low-dose
      anticoagulants for VTE prophylaxis have not been firmly established in this
      patient population. However, recent studies also indicate pharmacologic VTE
      prophylaxis can be used with caution in hospitalized patients with chronic liver
      disease. 

PMID- 25989434
TI  - Chest discomfort in a patient with cancer.
AB  - Patients with cancer are at higher risk for venous thromboembolism than patients
      without cancer due to hypercoagulability associated with malignancy. This article
      describes a patient with metastatic renal cell carcinoma who had chest pain over
      several weeks caused by multiple pulmonary emboli. 

PMID- 25989435
TI  - Surgical management of breast cancer.
AB  - This article reviews the surgical options for breast cancer with emphasis on
      factors that influence decision making and the data that have driven changes in
      clinical practice. 

PMID- 25989436
TI  - Physician assistant wages and employment, 2000-2025.
AB  - This study sought to assess physician assistant (PA) wages, make comparisons with
      other healthcare professionals, and project their earnings to 2025. The Bureau of
      Labor Statistics PA employment datasets were probed, and 2013 wages were used to
      explore median wage differences between large employer categories and 14 years of
      historical data (2000-2013). Median wages of PAs, family physicians and general
      practitioners, pharmacists, registered nurses, advanced practice nurses, and
      physical therapists were compared. Linear regression was used to project the PA
      median wage to 2025. In 2013, the median hourly wage for a PA employed in a
      clinical role was $44.70. From 2000 to 2013, PA wages increased by 40% compared
      with the cumulative inflation rate of 35.3%. This suggests that demand exceeds
      supply, a finding consistent with similar clinicians such as family physicians. A
      predictive model suggests that PA employment opportunities and remuneration will
      remain high through 2025. 

PMID- 25989437
TI  - Tetralogy of Fallot.

PMID- 25989438
TI  - An unexpectedly painful limb.

PMID- 25989439
TI  - Lessons learned from the brute beast.

PMID- 25989441
TI  - Olmsted syndrome in an Indian male with a new de novo mutation in TRPV3.

PMID- 25989440
TI  - An embryo of protocells: The capsule of graphene with selective ion channels.
AB  - The synthesis of artificial cell is a route for searching the origin of
      protocell. Here, we create a novel cell model of graphene capsules with selective
      ion channels, indicating that graphene might be an embryo of protocell membrane.
      Firstly, we found that the highly oxidized graphene and phospholipid-graphene
      oxide composite would curl into capsules under a strongly acidic saturated
      solution of heavy metallic salt solution at low temperature. Secondly, L-amino
      acids exhibited higher reactivity than D-amino acids on graphene oxides to form
      peptides, and the formed peptides in the influence of graphene would be
      transformed into a secondary structure, promoting the formation of left-handed
      proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused
      (84)Kr(25+), has a high selectivity for permeation of the monovalent metal ions (
      Rb(+) > K(+) > Cs(+) > Na(+) > Li(+), based on permeation concentration), but
      does not allow Cl(-) go through. It is similar to K(+) channels, which would
      cause an influx of K(+) into capsule of graphene with the increase of pH in the
      primitive ocean, creating a suitable inner condition for the origin of life.
      Therefore, we built a model cell of graphene, which would provide a route for
      reproducing the origin of life. 

PMID- 25989442
TI  - An anatomical and psychophysical comparison of subjective verticals in patients
      with right brain damage.
AB  - INTRODUCTION: Brain hemisphere lesions often cause a contralesional tilt of the
      subjective vertical (SV) a phenomenon related to spatial neglect and postural
      disorders. Depending on the method employed, different perceptual systems come
      into play when this gravitational vertical is assessed. Here, we compared the
      anatomical and psychophysical characteristics of modality-dependent SV biases in
      patients with right hemisphere stroke. METHODS: The SV was measured with visual,
      haptic and visual-haptic modalities (SV, SVV, SVHV) in 46 patients with a
      relatively recent stroke. Voxel-based lesion-symptom mapping (performed with
      NPM((r))) was used to highlight brain areas in which lesions best explained the
      severity of task biases (p < .05). RESULTS: Lesions explaining the SVV tilt
      (TSVV) were centered on the posterior part of the middle temporal gyrus, those
      explaining the TSHV were more limited and anterior, without convergence with the
      former. Lesions explaining the TSVHV were centered on the superior temporal gyrus
      and more anterior those explaining the TSVV, with convergence with lesions
      explaining both the TSVV and the TSHV. Patients showed counterclockwise
      deviations in the SVs. Constant and variable errors were greater for the SHV than
      for the SVV and for the SVHV. The TSVV and TVHV were closely related to the
      presence of left spatial neglect and hemianopia. CONCLUSIONS: Errors in the SVV
      and (at a lesser degree) SVHV were preferentially related to lesions in visual
      associative cortex. The SVV and especially the SVHV provide valuable estimates of
      patient difficulties, in view of the lower associated variable errors (i.e.,
      greater precision) and closer relationships with clinical disorders.

PMID- 25989445
TI  - Photoinduced Electron Transfer of PAMAM Dendrimer-Zinc(II) Porphyrin Associates
      at Polarized Liquid|Liquid Interfaces.
AB  - The heterogeneous photoinduced electron-transfer reaction of the ion associates
      between NH2-terminated polyamidoamine (PAMAM) dendrimers and 5,10,15,20
      tetrakis(4-sulfonatophenyl)porphyrinato zinc(II) (ZnTPPS(4-)) was studied at the
      polarized water|1,2-dichloroethane (DCE) interface. The positive photocurrent
      arising from the photoreduction of ZnTPPS(4-) by a lipophilic quencher,
      decamethylferrocene, in the interfacial region was significantly enhanced by the
      ion association with the PAMAM dendrimers. The photocurrent response of the
      dendrimer-ZnTPPS(4-) associates was dependent on the pH condition and on the
      generation of dendrimer. A few cationic additives such as polyallylamine and n
      octyltrimethyammonium were also examined as alternatives to the PAMAM dendrimer,
      but the magnitude of the photocurrent enhancement was rather small. The high
      photoreactivity of the dendrimer-ZnTPPS(4-) associates was interpreted mainly as
      a result of the high interfacial concentration of photoreactive porphyrin units
      associated stably with the dendrimer which was preferably adsorbed at the
      polarized water|DCE interface. The photochemical data observed in the second and
      fourth generation PAMAM dendrimer systems demonstrated that the higher generation
      dendrimer which can incorporate a porphyrin molecule more completely in the
      interior is less efficient for the photocurrent enhancement at the interface.
      These results indicated that the photoreactivity of ionic reactant at a polarized
      liquid|liquid interface can readily be modified via ion association with the
      charged dendrimer. 

PMID- 25989444
TI  - Neural mechanisms of the spacing effect in episodic memory: A parallel EEG and
      fMRI study.
AB  - Although behavioral studies have consistently reported the spacing effect in
      learning, its cognitive and neural mechanisms are still not clearly elucidated.
      According to the storage/retrieval strength framework proposed by Bjork (1999;
      Bjork & Bjork, 1992), which was built on the study-phase retrieval hypothesis and
      the deficient processing hypothesis, the spacing effect is achieved by reducing
      memomtary retrieval strength during subsequent repetitions and thus enhancing
      storage strength. The present study tested this hypothesis with parallel fMRI and
      EEG. Participants were asked to study 180 words that were repeated three times,
      with half of the words having an inter-repetition-lag of 1-3 words (i.e., massed
      learning) and the other half an inter-repetition-lag of 25-35 words (i.e., spaced
      learning). An unexpected recognition test was administered 24 h after learning.
      Consistent with Bjork's hypothesis, the EEG data suggested that spaced learning
      was associated with weaker retrieval strength, as indicated by a reduced
      familiarity effect in frontal N400. Meanwhile, spaced learning effectively
      enhanced the encoding process and thus led to stronger storage strength, as
      indicated by greater fMRI responses during learning in brain regions whose
      activities were associated with subsequent memory. Interestingly, no direct
      association was found between repetition priming and episodic memory. These
      results furthered our understanding of the neural mechanisms underlying the
      spacing effect. 

PMID- 25989443
TI  - Speech entrainment compensates for Broca's area damage.
AB  - Speech entrainment (SE), the online mimicking of an audiovisual speech model, has
      been shown to increase speech fluency in patients with Broca's aphasia. However,
      not all individuals with aphasia benefit from SE. The purpose of this study was
      to identify patterns of cortical damage that predict a positive response SE's
      fluency-inducing effects. Forty-four chronic patients with left hemisphere stroke
      (15 female) were included in this study. Participants completed two tasks: 1)
      spontaneous speech production, and 2) audiovisual SE. Number of different words
      per minute was calculated as a speech output measure for each task, with the
      difference between SE and spontaneous speech conditions yielding a measure of
      fluency improvement. Voxel-wise lesion-symptom mapping (VLSM) was used to relate
      the number of different words per minute for spontaneous speech, SE, and SE
      related improvement to patterns of brain damage in order to predict lesion
      locations associated with the fluency-inducing response to SE. Individuals with
      Broca's aphasia demonstrated a significant increase in different words per minute
      during SE versus spontaneous speech. A similar pattern of improvement was not
      seen in patients with other types of aphasia. VLSM analysis revealed damage to
      the inferior frontal gyrus predicted this response. Results suggest that SE
      exerts its fluency-inducing effects by providing a surrogate target for speech
      production via internal monitoring processes. Clinically, these results add
      further support for the use of SE to improve speech production and may help
      select patients for SE treatment. 

PMID- 25989446
TI  - Alumina-entrapped Ag catalyzed nitro compounds coupled with alcohols using
      borrowing hydrogen methodology.
AB  - Supported silver catalysts were reported for the first time to be able to
      catalyze the coupling reaction between nitroarenes and alcohols via the borrowing
      hydrogen scheme. The recyclable, non-leaching catalyst is synthesized by the
      entrapment method, which allows entrapping of silver nanoparticles in an alumina
      matrix. Alcohols, acting as the reducing agents for nitro-groups, alkylated the
      resultant amines smoothly over these silver catalysts giving a yield of >98%
      towards the N-substituted amines. In this process, multiple steps were realized
      in one-pot over a single catalyst with very high efficiency. It offers another
      clean and economic way to achieve amination of alcohols. 

PMID- 25989447
TI  - Molecular signatures of vaccine adjuvants.
AB  - Mass vaccination has saved millions of human lives and improved the quality of
      life in both developing and developed countries. The emergence of new pathogens
      and inadequate protection conferred by some of the existing vaccines such as
      vaccines for tuberculosis, influenza and pertussis especially in certain age
      groups have resulted in a move from empirically developed vaccines toward more
      pathogen tailored and rationally engineered vaccines. A deeper understanding of
      the interaction of innate and adaptive immunity at molecular level enables the
      development of vaccines that selectively target certain type of immune responses
      without excessive reactogenicity. Adjuvants constitute an imperative element of
      modern vaccines. Although a variety of candidate adjuvants have been evaluated in
      the past few decades, only a limited number of vaccine adjuvants are currently
      available for human use. A better understanding of the mode of action of
      adjuvants is pivotal to harness the potential of existing and new adjuvants in
      shaping a desired immune response. Recent advancement in systems biology powered
      by the emerging cutting edge omics technology has led to the identification of
      molecular signatures rapidly induced after vaccination in the blood that
      correlate and predict a later protective immune response or vaccine safety. This
      can pave ways to prospectively determine the potency and safety of vaccines and
      adjuvants. This review is intended to highlight the importance of big data
      analysis in advancing our understanding of the mechanisms of actions of adjuvants
      to inform rational development of future human vaccines. 

PMID- 25989448
TI  - Effectiveness of Rubella vaccine in a rubella outbreak in Guangzhou city, China,
      2014.
AB  - BACKGROUND: WHO recommends the use of rubella-containing vaccine (RCVs) to
      prevent rubella and congenital rubella syndrome (CRS). Most licensed rubella
      vaccines in use globally are based on RA27/3 strains and have estimated vaccine
      effectiveness (VE) rates of 95-100%. In contrast, China uses a BRD-II strain
      based rubella vaccine. Few field studies have been conducted that estimate VE of
      China's RCV. On March 17, 2014, a rubella outbreak was reported in a middle
      school in Guangzhou city, China. We conducted an investigation to understand
      reasons for the outbreak, and we used that investigation to estimate vaccine
      effectiveness of China's rubella vaccine. METHODS: To identify cases,
      investigators reviewed records kept by the school doctor and absentee records
      kept by teachers. Self-administered questionnaires were sent to parents of all
      students to collect information about the students' symptoms, the results of any
      physician consultation, and disease history. We obtained demographic information
      and illness information for all students in the school; vaccination status was
      determined by inspection of official, parent-held vaccination records. A
      retrospective cohort study was conducted in 13 classes that had secondary cases
      of rubella. Using the secondary attack rates, we evaluated VE by the number of
      RCV doses received and age at vaccination. RESULTS: During the period February 17
      May 23, 2014, 162 students (50 suspected cases, 88 probable cases, 24 confirmed
      cases) were diagnosed with rubella, yielding an overall attack rate of 10%
      (162/1621). Cases occurred in 27 classes (73%) of 37 classrooms. Secondary cases
      occurred in 13 classes (35%) of 37 classrooms. A total of 1130 students (69.7%)
      have vaccination certificates; 419 (37%) students were record-confirmed to have
      received RCV. For those vaccinated using BRD-II strain vaccine, vaccine
      effectiveness (VE) was 94% (95%CI: 75-98). VE for measles, mumps, and rubella
      (MMR) vaccine which is based on either BRD-II or RA27/3 strain was 89% (95%CI: 56
      97). VE of a single dose of domestic monovalent rubella vaccine that used BRD-II
      strain vaccine was 93% (95%CI: 73-98). VE for those who received the vaccine
      between 1 and 2 years of age was 95% (95% CI: 67-99) while the VE was 100% for
      those vaccinated after 2 years of age. VE among those who received RCV <12 years
      ago was 100% while VE among those who received RCV >=12 years ago was 92% (95%CI:
      70-98). CONCLUSIONS: The rubella vaccines used in China that are based on the BRD
      II rubella vaccine strain have VE of 94%, which is similar to the more commonly
      used RA27/3-based RCVs. Low vaccination coverage contributed to this outbreak;
      early reporting of an outbreak is necessary for effective outbreak response
      immunization.

PMID- 25989450
TI  - Avoiding compression of the DIEP pedicle at inset.

PMID- 25989449
TI  - The dengue vaccine pipeline: Implications for the future of dengue control.
AB  - Dengue has become the most rapidly expanding mosquito-borne infectious disease on
      the planet, surpassing malaria and infecting at least 390 million people per
      year. There is no effective treatment for dengue illness other than supportive
      care, especially for severe cases. Symptoms can be mild or life-threatening as in
      dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only
      partially successful in decreasing dengue transmission. The potential use of safe
      and effective tetravalent dengue vaccines is an attractive addition to prevent
      disease or minimize the possibility of epidemics. There are currently no licensed
      dengue vaccines. This review summarizes the current status of all dengue vaccine
      candidates in clinical evaluation. Currently five candidate vaccines are in human
      clinical trials. One has completed two Phase III trials, two are in Phase II
      trials, and three are in Phase I testing. 

PMID- 25989451
TI  - Structure of Slitrk2-PTPdelta complex reveals mechanisms for splicing-dependent
      trans-synaptic adhesion.
AB  - Selective binding between pre- and postsynaptic adhesion molecules can induce
      synaptic differentiation. Here we report the crystal structure of a synaptogenic
      trans-synaptic adhesion complex between Slit and Trk-like family member 2
      (Slitrk2) and receptor protein tyrosine phosphatase (RPTP) delta. The structure
      and site-directed mutational analysis revealed the structural basis of splicing
      dependent adhesion between Slitrks and type IIa RPTPs for inducing synaptic
      differentiation. 

PMID- 25989452
TI  - Chronic effects of the ionic liquid [C4mim][Cl] towards the microalga Scenedesmus
      quadricauda.
AB  - Chronic effects of the ionic liquid [C4mim][Cl] (mp 73  degrees C) towards the
      microalga, Scenedesmus quadricauda were studied by flow cytometry, monitoring
      multiple endpoints of cell density, esterase activity, membrane integrity,
      reactive oxygen species and chlorophyll fluorescence. Toxicity was clearly in
      evidence, and although increased esterase activity indicated hormesis during
      initial exposure to [C4mim][Cl], inhibition of both esterase activity and
      chlorophyll fluorescence became apparent after 3 days. Cell density was also
      decreased by culturing with [C4mim][Cl], but this effect was clearly
      concentration-dependent and only became significant during the second half of the
      experiment. In contrast, [C4mim][Cl] had only a modest effect on reactive oxygen
      species (ROS) and caused little damage to cell membranes. 

PMID- 25989453
TI  - Combined thermal and herbicide stress in functionally diverse coral symbionts.
AB  - Most reef building corals rely on symbiotic microalgae (genus Symbiodinium) to
      supply a substantial proportion of their energy requirements. Functional
      diversity of different Symbiodinium genotypes, endorsing the host with
      physiological advantages, has been widely reported. Yet, the influence of
      genotypic specificity on the symbiont's susceptibility to contaminants or
      cumulative stressors is unknown. Cultured Symbiodinium of presumed thermal
      tolerant clade D tested especially vulnerable to the widespread herbicide diuron,
      suggesting important free-living populations may be at risk in areas subjected to
      terrestrial runoff. Co-exposure experiments where cultured Symbiodinium were
      exposed to diuron over a thermal stress gradient demonstrated how fast-growing
      clade C1 better maintained photosynthetic capability than clade D. The mixture
      toxicity model of Independent Action, considering combined thermal stress and
      herbicide contamination, revealed response additivity for inhibition of
      photosynthetic yield in both tested cultures, emphasizing the need to account for
      cumulative stressor impacts in ecological risk assessment and resource
      management. 

PMID- 25989454
TI  - Characteristics of air pollutant dispersion around a high-rise building.
AB  - A numerical wind tunnel model was proposed. The computed results of the pollutant
      diffusion around a typical Hong Kong high-rise building model (at a linear scale
      of 1:30), were found to show a similar trend to the outcomes of self-conducted
      experimental measurements that the pathways of pollutant migration for windward
      and leeward pollutant emission are different. For the case with windward
      pollutant emission at the 3rd floor within a re-entry, the pollutant migrated
      downwards due to the downwash created by the wind. In contrast, for the case with
      leeward pollution emission, dispersion is dominated by intense turbulent mixing
      in the near wake and characterized by the upward migration of the pollutant in
      the leeward re-entry. The simulated results of haze-fog (HF) studies confirm that
      the pathway of pollutant migration is dominated by wind-structure interaction and
      buoyancy effect only plays a minor role in the dispersion process. 

PMID- 25989455
TI  - Spectrum of Muscle Histopathologic Findings in Forty-Two Scleroderma Patients
      With Weakness.
AB  - OBJECTIVE: To determine if distinct muscle pathologic features exist in
      scleroderma subjects with weakness. METHODS: This retrospective study included
      weak scleroderma subjects with muscle biopsies available for review. Biopsies
      were systematically assessed for individual pathologic features, including
      inflammation, necrosis, fibrosis, and acute neurogenic atrophy. Based on the
      aggregate individual features, biopsies were assigned a histopathologic category
      of polymyositis, dermatomyositis, necrotizing myopathy, nonspecific myositis,
      "acute denervation," "fibrosis only," or "other." Clinical data analyzed included
      autoantibody profiles, scleroderma subtype and disease duration, Medsger muscle
      severity scores, creatine kinase, electromyography, and muscle magnetic resonance
      imaging. RESULTS: A total of 42 subjects (79% female and 64% diffuse scleroderma)
      were included in this study. Necrosis (67%), inflammation (48%), acute neurogenic
      atrophy (48%), and fibrosis (33%) were the most prevalent pathologic features.
      The presence of fibrosis was strongly associated with anti-PM-Scl antibodies.
      Histopathologic categories included nonspecific myositis (36%), necrotizing
      myopathy (21%), dermatomyositis (7%), "acute denervation" (7%), "fibrosis only"
      (7%), and polymyositis (5%). Disease duration of scleroderma at the time of
      muscle biopsy was shorter in polymyositis than other histopathologic categories.
      Patients with anti-PM-Scl and Scl-70 antibodies also had a shorter disease
      duration than those with other autoantibody profiles. CONCLUSION: Nonspecific
      myositis and necrotizing myopathy were the most common histopathologic categories
      in weak scleroderma subjects. Surprisingly, nearly half of the subjects studied
      had histologic evidence of acute motor denervation (acute neurogenic atrophy);
      this has not been previously reported. Taken together, these observations suggest
      that a variety of pathologic mechanisms may underlie the development of myopathy
      in scleroderma.

PMID- 25989456
TI  - Dose-response relationship between antimicrobial drugs and livestock-associated
      MRSA in pig farming.
AB  - The farming community can be a vehicle for introduction of livestock-associated
      methicillin-resistant Staphylococcus aureus (LA-MRSA) in hospitals. During 2011
      2013, an 18-month longitudinal study aimed at reducing the prevalence of LA-MRSA
      was conducted on 36 pig farms in the Netherlands. Evaluations every 6 months
      showed a slight decrease in MRSA prevalence in animals and a stable prevalence in
      farmers and family members. Antimicrobial use, expressed as defined daily dosages
      per animal per year, decreased 44% during the study period and was associated
      with declining MRSA prevalence in pigs. MRSA carriage in animals was
      substantially higher at farms using cephalosporins. Antimicrobial use remained
      strongly associated with LA-MRSA in humans regardless of the level of animal
      contact. A risk factor analysis outlined potential future interventions for LA
      MRSA control. These results should encourage animal and public health authorities
      to maintain their efforts in reducing antimicrobial use in livestock and ask for
      future controlled intervention studies. 

PMID- 25989457
TI  - One-step purification and concentration of DNA in porous membranes for point-of
      care applications.
AB  - The emergence of rapid, user-friendly, point-of-care (POC) diagnostic systems is
      paving the way for better disease diagnosis and control. Lately, there has been a
      strong emphasis on developing molecular-based diagnostics due to their potential
      for greatly increased sensitivity and specificity. One of the most critical steps
      in developing practical diagnostic systems is the ability to perform sample
      preparation, especially the purification of nucleic acids (NA), at the POC. As
      such, we have developed a simple-to-use, inexpensive, and disposable sample
      preparation system for in-membrane purification and concentration of NAs. This
      system couples lateral flow in a porous membrane with chitosan, a linear
      polysaccharide that captures NAs via anion exchange chromatography. The system
      can also substantially concentrate the NAs. The combination of these capabilities
      can be used on a wide range of sample types, which are prepared for use in
      downstream processes, such as qPCR, without further purification. 

PMID- 25989458
TI  - Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for
      Th1, Th2, Th17, and iNKT-cell cytokine production.
AB  - Itk(-/-) mice exhibit defects in the activation, development, and function of
      CD4(+) and CD8(+) T cells and iNKT cells. These and other defects in these mice
      make it difficult to uncouple the developmental versus functional requirement of
      Itk signaling. Here, we report an allele-sensitive mutant of Itk (Itkas) whose
      catalytic activity can be selectively inhibited by analogs of the PP1 kinase
      inhibitor. We show that Itkas behaves like WT Itk in the absence of the inhibitor
      and can rescue the development of Itk(-/-) T cells in mice. Using mice carrying
      Itkas, we show using its inhibitor that Itk activity is required not only for
      Th2, Th17, and iNKT-cell cytokine production, but also surprisingly, for Th1
      cytokine production. This work has important implications for understanding the
      role of Itk signaling in the development versus function of iNKT cells, Th1, Th2,
      and Th17 cells. 

PMID- 25989459
TI  - Inactivation of Vibrio parahaemolyticus by antimicrobial photodynamic technology
      using methylene blue.
AB  - BACKGROUND: Vibrio parahaemolyticus is the leading causative pathogen of
      gastroenteritis often related to contaminated seafood. Photodynamic inactivation
      has been recently proposed as a strategy for killing cells and viruses. The
      objective of this study was to verify the bactericidal effects caused by
      photodynamic inactivation using methylene blue (MB) over V. parahaemolyticus via
      flow cytometry, agarose gel electrophoresis and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Vibrio parahaemolyticus counts were
      determined using the most probable number method. A scanning electron microscope
      and a transmission electron microscope were employed to intuitively analyze
      internal and external cell structure. RESULTS: Combination of MB and laser
      treatment significantly inhibited the growth of V. parahaemolyticus. The
      inactivation rate of V. parahaemolyticus was >99.99% and its counts were reduced
      by 5 log10 in the presence of 0.05 mg mL(-1) MB when illuminated with visible
      light (power density 200 mW cm(-2)) for 25 min. All inactivated cells showed
      morphological changes, leakage of cytoplasm and degradation of protein and DNA.
      CONCLUSION: Results from this study indicated that photodynamic technology using
      MB produced significant inactivation of V. parahaemolyticus mainly brought about
      by the degradation of protein and DNA.

PMID- 25989461
TI  - Cobalt-Catalyzed Dual Annulation of o-Halobenzaldimine with Alkyne: A Powerful
      Route toward Bioactive Indenoisoquinolinones.
AB  - A cobalt-catalyzed dual annulation reaction for the synthesis of variously
      substituted indenoisoquinolinones from 2-bromobenzaldehydes, amines, and methyl 2
      (ethynyl)benzoates has been developed. This method could also be applied to the
      synthesis of an array of highly functionalized bioactive indenoisoquinolinones
      and their derivatives. A possible mechanism of the cobalt catalysis is proposed,
      involving imine formation from bromobenzaldehyde and the amine, followed by a
      series of oxidative addition, alkyne insertion, cyclization reactions, and carbon
      carbon double-bond migration. The regioselective alkyne insertion plays an
      important role for the success of the second annulation. 

PMID- 25989460
TI  - Urinary Kidney injury molecule-1 can predict delayed graft function in living
      donor renal allograft recipients.
AB  - AIM: Delayed graft function is an early complication leading to impaired
      creatinine clearance, urine formation and determinant of long term graft outcome.
      The aim of the present study was to determine the earliest predictive cut-off
      value of uKIM-1 level in patients with delayed graft function and acute tubular
      necrosis. METHODS: We have determined the serial urinary KIM-1 normalized to
      urinary creatinine (uKIM-1, pg/mg) level at 0, 6, 12, 18, 24 and 48 h of post
      transplant by ELISA methods. RESULT: The normalized uKIM-1 and AUC-ROC, of uKIM-1
      were progressively increased up to 48 h in both delayed graft function (DGF) and
      immediate graft function (IGF). The u KIM-1 values were significantly high at 6,
      12, 18, 24 and 48 h in patients with DGF as compared to that of IGF except at
      half an hour post-transplant values. Although, progressive increase in uKIM-1
      values were observed in both groups of patients; there was an overlap of values
      between two groups up to 12 h. The earliest non-overlapping values of uKIM-1
      between the groups were observed at 18 h onwards and minimum difference of 923.43
      pg/mg. The earliest predictive AUC-ROC of uKIM-1 in patients with DGF without
      overlap with IGF was also observed at 18 h post-transplant with specificity of
      100% and sensitivity of 89.9%. CONCLUSION: Serial uKIM-1 measurement can be used
      as non-invasive diagnostic biomarkers to predict the incident of DGF in living
      donor renal transplant recipients. At 18(th) post-transplant hour uKIM-1 can
      predict DGF with 100% specificity and 89.9% sensitivity with a cut-off value of
      normalized KIM-1 of 923.43 pg/mg.

PMID- 25989462
TI  - Cucurbit[6]uril: A Possible Host for Noble Gas Atoms.
AB  - Density functional and ab initio molecular dynamics studies are carried out to
      investigate the stability of noble gas encapsulated cucurbit[6]uril (CB[6])
      systems. Interaction energy, dissociation energy and dissociation enthalpy are
      calculated to understand the efficacy of CB[6] in encapsulating noble gas atoms.
      CB[6] could encapsulate up to three Ne atoms having dissociation energy (zero
      point energy corrected) in the range of 3.4-4.1 kcal/mol, whereas due to larger
      size, only one Ar or Kr atom encapsulated analogues would be viable. The
      dissociation energy value for the second Ar atom is only 1.0 kcal/mol. On the
      other hand, the same for the second Kr is -0.5 kcal/mol, implying the instability
      of the system. The noble gas dissociation processes are endothermic in nature,
      which increases gradually along Ne to Kr. Kr encapsulated analogue is found to be
      viable at room temperature. However, low temperature is needed for Ne and Ar
      encapsulated analogues. The temperature-pressure phase diagram highlights the
      region in which association and dissociation processes of Kr@CB[6] would be
      favorable. At ambient temperature and pressure, CB[6] may be used as an effective
      noble gas carrier. Wiberg bond indices, noncovalent interaction indices, electron
      density, and energy decomposition analyses are used to explore the nature of
      interaction between noble gas atoms and CB[6]. Dispersion interaction is found to
      be the most important term in the attraction energy. Ne and Ar atoms in one Ng
      entrapped analogue are found to stay inside the cavity of CB[6] throughout the
      simulation at 298 K. However, during simulation Ng2 units in Ng2@CB[6] flip
      toward the open faces of CB[6]. After 1 ps, one Ne atom of Ne3@CB[6] almost
      reaches the open face keeping other two Ne atoms inside. At lower temperature (77
      K), all the Ng atoms in Ngn@CB[6] remain well inside the cavity of CB[6]
      throughout the simulation time (1 ps). 

PMID- 25989463
TI  - In Situ Investigation of Li and Na Ion Transport with Single Nanowire
      Electrochemical Devices.
AB  - In the past decades, Li ion batteries are widely considered to be the most
      promising rechargeable batteries for the rapid development of mobile devices and
      electric vehicles. There arouses great interest in Na ion batteries, especially
      in the field of static grid storage due to their much lower production cost
      compared with Li ion batteries. However, the fundamental mechanism of Li and Na
      ion transport in nanoscale electrodes of batteries has been rarely experimentally
      explored. This insight can guide the development and optimization of high
      performance electrode materials. In this work, single nanowire devices with
      multicontacts are designed to obtain detailed information during the
      electrochemical reactions. This unique platform is employed to in situ
      investigate and compare the transport properties of Li and Na ions at a single
      nanowire level. To give different confinement for ions and electrons during the
      electrochemical processes, two different configurations of nanowire electrode are
      proposed; one is to fully immerse the nanowire in the electrolyte, and the other
      is by using photoresist to cover the nanowire with only one end exposed. For both
      configurations, the conductivity of nanowire decreases after
      intercalation/deintercalation for both Li and Na ions, indicating that they share
      the similar electrochemical reaction mechanisms in layered electrodes. However,
      the conductivity degradation and structure destruction for Na ions is more severe
      than those of Li ions during the electrochemical processes, which mainly results
      from the much larger volume of Na ions and greater energy barrier encountered by
      the limited layered spaces. Moreover, the battery performances of coin cells are
      compared to further confirm this conclusion. The present work provides a unique
      platform for in situ electrochemical and electrical probing, which will push the
      fundamental and practical research of nanowire electrode materials for energy
      storage applications. 

PMID- 25989464
TI  - Assessing fatigue in inflammatory bowel disease: comparison of three fatigue
      scales.
AB  - BACKGROUND: Fatigue is commonly reported by patients with inflammatory bowel
      disease (IBD), both in quiescent and active disease. Few fatigue scales have been
      tested in IBD. AIM: To assess three fatigue assessment scales in IBD and to
      determine correlates of fatigue. METHODS: Potential participants (n = 2131) were
      randomly selected from an IBD organisation's members' database; 605 volunteered
      and were posted three fatigue scales: Inflammatory Bowel Disease Fatigue scale,
      Multidimensional Fatigue Inventory and Multidimensional Assessment Fatigue scale
      and questionnaires assessing anxiety, depression, quality of life (QoL) and IBD
      activity. The questionnaires were tested for stability over time with another
      group (n = 70) of invited participants. Internal consistency was measured by
      Cronbach's alpha and test-retest reliability by the intraclass correlation
      coefficient (ICC). RESULTS: Four hundred and sixty-five of 605 (77%)
      questionnaires were returned; of 70 invited, 48/70 returned test (68.6%) and
      41/70 (58.6%) returned retest. The three scales are highly correlated (P <
      0.001). Test-retest suggests reasonable agreement with ICC values between 0.65
      and 0.84. Lower age, female gender, IBD diagnosis, anxiety, depression and QoL
      were associated with fatigue (P < 0.001) on univariable analysis. However, on
      multivariable analysis only depression and low QoL were consistently associated
      with fatigue, while female gender was associated on most scales. IBD diagnosis,
      age and other factors were not consistently associated with severity or impact of
      fatigue once other variables were controlled for. CONCLUSIONS: All three fatigue
      scales are likely to measure IBD fatigue adequately. Responsiveness to change has
      not been tested. Depression, poorer QoL and probably female gender are the major
      associations of fatigue in IBD.

PMID- 25989466
TI  - Potentially preventable hospital separations related to oral health: a 10-year
      analysis.
AB  - BACKGROUND: The aims of this study were to assess the rates of hospitalizations
      for potentially preventable dental conditions over a 10-year period in Western
      Australia; to analyse trends over 10 years in rate changes of hopitalizations;
      and to analyse the mix of preventable dental conditions by age group and
      Aboriginal status. METHODS: The principal diagnosis, as classified by the
      International Classification of Disease (ICD-10AM), was used to select
      hospitalization data for all patients who were discharged from hospital in
      Western Australia for the financial years 1999-2000 to 2008-2009, for a
      potentially preventable oral health condition. RESULTS: Over a 10-year period
      more than 65 000 people were hospitalized. Population rates of hospitalization
      increased significantly over the period for both Aboriginal and non-Aboriginal
      population groups. Admission rates were higher for Aboriginal people. Children
      under 14 were more likely to be admitted; the most common condition that required
      hospitalization was dental caries, and the highest rates of hospitalization were
      for those from the most socio-economically disadvantaged areas. CONCLUSIONS:
      These hospitalizations remain a considerable and increasing financial burden on
      health budgets. An increase in efforts is necessary to curb escalating government
      health expenditure by reducing avoidable and preventable oral health related
      hospitalizations.

PMID- 25989465
TI  - Cost implications of implementation of pathogen-inactivated platelets.
AB  - BACKGROUND: Pathogen inactivation (PI) is a new approach to blood safety that may
      introduce additional costs. This study identifies costs that could be eliminated,
      thereby mitigating the financial impact. STUDY DESIGN AND METHODS: Cost
      information was obtained from five institutions on tests and procedures (e.g.,
      irradiation) currently performed, that could be eliminated. The impact of
      increased platelet (PLT) availability due to fewer testing losses, earlier entry
      into inventory, and fewer outdates with a 7-day shelf life were also estimated.
      Additional estimates include costs associated with managing (1) special requests
      and (2) test results, (3) quality control and proficiency testing, (4) equipment
      acquisition and maintenance, (5) replacement of units lost to positive tests, (6)
      seasonal or geographic testing, and (7) health department interactions. RESULTS:
      All costs are mean values per apheresis PLT unit in USD ($/unit). The estimated
      test costs that could be eliminated are $71.76/unit and a decrease in transfusion
      reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and
      dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit,
      while decreased outdating with 7-day storage can be amortized to $16.89/unit.
      Total potential costs saved with PI is $141.65/unit. Costs are influenced by a
      variety of factors specific to institutions such as testing practices and the
      location in which such costs are incurred and careful analysis should be
      performed. Additional benefits, not quantified, include retention of some
      currently deferred donors and scheduling flexibility due to 7-day storage.
      CONCLUSIONS: While PI implementation will result in additional costs, there are
      also potential offsetting cost reductions, especially after 7-day storage
      licensing.

PMID- 25989467
TI  - Dental implants inserted in male versus female patients: a systematic review and
      meta-analysis.
AB  - The aim of this meta-analysis was to test the null hypothesis of no difference in
      the failure rates, marginal bone loss (MBL) and post-operative infection for
      implants inserted in male or female patients, against the alternative hypothesis
      of a difference. An electronic search without time or language restrictions was
      undertaken in December 2014. Eligibility criteria included clinical human
      studies, either randomized or not. Ninety-one publications were included, with a
      total of 27,203 implants inserted in men (1185 failures), and 25,154 implants
      inserted in women (1039 failures). The results suggest that the insertion of
      dental implants in male patients statistically affected the implant failure rates
      (RR 1.21, 95% CI 1.07-1.37, P = 0.002). Due to the limited number of studies
      reporting results on MBL, it is difficult to estimate the real effect of the
      insertion of implants in different sexes on the marginal bone level. Due to lack
      of satisfactory information, meta-analysis for the outcome 'post-operative
      infection' was not performed. The results have to be interpreted with caution due
      to the presence of several confounding factors in the included studies.

PMID- 25989468
TI  - Deletion of Smgpi1 encoding a GPI-anchored protein suppresses sterility of the
      STRIPAK mutant DeltaSmmob3 in the filamentous ascomycete Sordaria macrospora.
AB  - The striatin interacting phosphatase and kinase (STRIPAK) complex, which is
      composed of striatin, protein phosphatase PP2A and kinases, is required for
      fruiting-body development and cell fusion in the filamentous ascomycete Sordaria
      macrospora. Here, we report on the interplay of the glycosylphosphatidylinositol
      (GPI)-anchored protein SmGPI1 with the kinase activator SmMOB3, a core component
      of human and fungal STRIPAK complexes. SmGPI1 is conserved among filamentous
      ascomycetes and was first identified in a yeast two-hybrid screen using SmMOB3 as
      bait. The physical interaction of SmMOB3 and SmGPI1 was verified by co
      immunoprecipitation. In vivo localization and differential centrifugation
      revealed that SmGPI1 is predominantly secreted and attached to the cell wall but
      is also associated with mitochondria and appears to be a dual-targeted protein.
      Deletion of Smgpi1 led to an increased number of fruiting bodies that were
      normally shaped but reduced in size. In addition, Smmob3 and Smgpi1 genetically
      interact. In the sterile DeltaSmmob3 background deletion of Smgpi1 restores
      fertility, vegetative growth as well as hyphal-fusion defects. The suppression
      effect was specific for the DeltaSmmob3 mutant as deletion of Smgpi1 in other
      STRIPAK mutants does not restore fertility. 

PMID- 25989469
TI  - Direct measurements of the optical cross sections and refractive indices of
      individual volatile and hygroscopic aerosol particles.
AB  - We present measurements of the evolving extinction cross sections of individual
      aerosol particles (spanning 700-2500 nm in radius) during the evaporation of
      volatile components or hygroscopic growth using a combination of a single
      particle trap formed from a Bessel light beam and cavity ring-down spectroscopy.
      For single component organic aerosol droplets of 1,2,6-hexanetriol, polyethylene
      glycol 400, and glycerol, the slow evaporation of the organic component (over
      time scales of 1000 to 10,000 s) leads to a time-varying size and extinction
      cross section that can be used to estimate the refractive index of the droplet.
      Measurements on binary aqueous-inorganic aerosol droplets containing one of the
      inorganic solutes ammonium bisulfate, ammonium sulfate, sodium nitrate, or sodium
      chloride (over time scales of 1000 to 15,000 s) under conditions of changing
      relative humidity show that extinction cross-section measurements are consistent
      with expectations from accepted models for the variation in droplet refractive
      index with hygroscopic growth. In addition, we use these systems to establish an
      experimental protocol for future single particle extinction measurements. The
      advantages of mapping out the evolving light extinction cross-section of an
      individual particle over extended time frames accompanied by hygroscopic cycling
      or component evaporation are discussed.

PMID- 25989470
TI  - Derivation and internal validation of an expanded cardiovascular risk prediction
      score for rheumatoid arthritis: a Consortium of Rheumatology Researchers of North
      America Registry Study.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of mortality in
      rheumatoid arthritis (RA), but CV risk prediction scores derived from the general
      population do not accurately predict CV risk in RA patients. The goal of these
      analyses was to develop and internally validate an expanded CV risk prediction
      score for RA. METHODS: Study participants were patients with RA and no known CVD
      from the Consortium of Rheumatology Researchers of North America registry. Two
      thirds of the cohort were used to derive the CV risk prediction score, and one
      third for internal validation. Traditional CV risk factors were included in the
      base Cox regression model, and RA-related variables were assessed in an expanded
      model predicting confirmed CV events. Fit and utility of the expanded model were
      evaluated. RESULTS: The study cohort included 23,605 RA patients with 437 CV
      events over a median followup of 2.2 years. The RA variables found to be
      significant in the regression models and included in the expanded risk model were
      disease activity (Clinical Disease Activity Index >10 versus <=10), disability
      (modified Health Assessment Questionnaire disability index >0.5 versus <=0.5),
      daily prednisone use (any versus none), and disease duration (>=10 years versus
      <10 years). The expanded model had good fit (Hosmer-Lemeshow goodness of fit P =
      0.94) and a lower Akaike's information criterion than the base model. In the
      internal validation cohort, the c-statistic for model discrimination was
      significantly improved from the base model to the expanded model (from 0.7261 to
      0.7609; P = 0.0104). The net reclassification index of CV risk in models using a
      4-category CV risk prediction tool was 40% (95% confidence interval 37-44%).
      CONCLUSION: This newly developed, expanded risk score for CV outcomes in RA
      performs well and improves the classification of CV risk in comparison to a risk
      prediction score in which only traditional risk factors were included.

PMID- 25989471
TI  - Palmoplantar Pustular Psoriasis Is Associated with Missense Variants in CARD14,
      but Not with Loss-of-Function Mutations in IL36RN in European Patients.

PMID- 25989473
TI  - Multibacillary leprosy in an active duty military member.

PMID- 25989472
TI  - Lack of Collagen VI Promotes Wound-Induced Hair Growth.
AB  - Collagen VI is an extracellular matrix molecule that is abundantly expressed in
      the skin. However, the role of collagen VI in hair follicle growth is unknown.
      Here, we show that collagen VI is strongly deposited in hair follicles, and is
      markedly upregulated by skin wounding. Lack of collagen VI in Col6a1(-/-) mice
      delays hair cycling and growth under physiological conditions, but promotes wound
      induced hair regrowth without affecting skin regeneration. Conversely, addition
      of purified collagen VI rescues the abnormal wound-induced hair regrowth in
      Col6a1(-/-) mice. Mechanistic studies revealed that the increased wound-induced
      hair regrowth of Col6a1(-/-) mice is triggered by activation of the Wnt/beta
      catenin signaling pathway, and is abolished by inhibition of this pathway. These
      findings highlight the essential relationships between extracellular matrix (ECM)
      and hair follicle regeneration, and suggest that collagen VI could be a potential
      therapeutic target for hair loss and other skin-related diseases. 

PMID- 25989474
TI  - Suppression of glucan, water dikinase in the endosperm alters wheat grain
      properties, germination and coleoptile growth.
AB  - Starch phosphate ester content is known to alter the physicochemical properties
      of starch, including its susceptibility to degradation. Previous work producing
      wheat (Triticum aestivum) with down-regulated glucan, water dikinase, the primary
      gene responsible for addition of phosphate groups to starch, in a grain-specific
      manner found unexpected phenotypic alteration in grain and growth. Here, we
      report on further characterization of these lines focussing on mature grain and
      early growth. We find that coleoptile length has been increased in these
      transgenic lines independently of grain size increases. No changes in starch
      degradation rates during germination could be identified, or any major alteration
      in soluble sugar levels that may explain the coleoptile growth modification. We
      identify some alteration in hormones in the tissues in question. Mature grain
      size is examined, as is Hardness Index and starch conformation. We find no
      evidence that the increased growth of coleoptiles in these lines is connected to
      starch conformation or degradation or soluble sugar content and suggest these
      findings provide a novel means of increasing coleoptile growth and early seedling
      establishment in cereal crop species. 

PMID- 25989475
TI  - The Subjective Experience of Pain: An FMRI Study of Percept-Related Models and
      Functional Connectivity.
AB  - OBJECTIVE: Previous work suggests that the perception of pain is subjective and
      dependent on individual differences in physiological, emotional, and cognitive
      states. Functional magnetic resonance imaging (FMRI) studies have used both
      stimulus-related (nociceptive properties) and percept-related (subjective
      experience of pain) models to identify the brain networks associated with pain.
      Our objective was to identify the network involved in processing subjective pain
      during cold stimuli. METHODS: The current FMRI study directly contrasted a
      stimulus-related model with a percept-related model during blocks of cold pain
      stimuli in healthy adults. Specifically, neuronal activation was modelled as a
      function of changes in stimulus intensity vs as a function of
      increasing/decreasing levels of subjective pain corresponding to changes in pain
      ratings. In addition, functional connectivity analyses were conducted to examine
      intrinsic correlations between three proposed subnetworks
      (sensory/discriminative, affective/motivational, and cognitive/evaluative)
      involved in pain processing. RESULTS: The percept-related model captured more
      extensive activation than the stimulus-related model and demonstrated an
      association between higher subjective pain and activation in expected cortical
      (dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, insula, dorsal
      anterior cingulate cortex [dACC] extending into pre-supplementary motor area) and
      subcortical (thalamus, striatum) areas. Moreover, connectivity results supported
      the posited roles of dACC and insula as key relay sites during neural processing
      of subjective pain. In particular, anterior insula appeared to link
      sensory/discriminative regions with regions in the other subnetworks, and dACC
      appeared to serve as a hub for affective/motivational, cognitive/evaluative, and
      motor subnetworks. CONCLUSIONS: Using a percept-related model, brain regions
      involved in the processing of subjective pain during the application of cold
      stimuli were identified. Connectivity analyses identified linkages between key
      subnetworks involved in processing subjective pain.

PMID- 25989476
TI  - Induction of ecdysteroidogenesis, methyl farnesoate synthesis and expression of
      ecdysteroid receptor and retinoid X receptor in the hepatopancreas and ovary of
      the giant mud crab, Scylla serrata by melatonin.
AB  - Melatonin, a chronobiotic molecule, is known to modulate several physiological
      functions in crustaceans including reproduction, molting and glucose homeostasis.
      In our earlier studies (Sainath and Reddy, 2010a), we observed hyperglycemia in
      crabs after melatonin administration and concluded that melatonin is another
      crustacean hyperglycemic hormone. In the current study, we have further examined
      the role of melatonin in regulating the levels of methyl farnesoate and
      ecdysteroid in the giant mud crab Scylla serrata and determined that melatonin
      indeed is a reproductive hormone. Further, we have determined partial nucleotide
      sequences of retinoid X receptor (RXR) and ecdysone receptor (EcR) in S. serrata
      and also studied the effect of melatonin on expression of these genes. Cloned RXR
      and EcR possess high sequence similarity with other Brachyuran genes.
      Administration of melatonin elevated circulatory methyl farnesoate (MF) and
      ecdysteroid levels in crabs. Since MF and ecdysteroid act through RXR and EcR
      respectively and these receptors are involved in the regulation of reproduction
      in crustaceans, we measured the expression levels of RXR and EcR in
      hepatopancreas and ovary after melatonin administration. The expression levels of
      both RXR and EcR increased significantly in the hepatopancreas and ovary of
      melatonin injected crabs when compared to the controls. In vitro culture of
      mandibular organ (MO) and Y-organ (YO) in the presence of melatonin resulted in a
      significant increase in the secretion of methyl farnesoate and ecdysteroid
      respectively. From the above studies it is clear that melatonin stimulates YO and
      MO, resulting in increased synthesis of ecdysteroids and methyl farnesoate, and
      thereby inducing reproduction in S. serrata. 

PMID- 25989477
TI  - Factors impeding the discovery of an intervention-based treatment for type 1
      diabetes.
AB  - Type 1 diabetes (T1D) is one of the most common and severe chronic diseases
      affecting both children and adults. The aetiology of the disease remains unknown,
      and thus far no 'true' cure for those affected is available. Indeed, exogenous
      insulin replacement therapy to manage glucose metabolism to the best degree
      possible remains the current standard of care. However, despite a recent array of
      truly impressive improvements designed to enhance disease management (e.g.
      insulin analogues, continuous glucose monitoring, insulin pumps), it is still
      difficult for the vast majority of patients to reach recommended target HbA1C
      levels (< 7.0%). As a result of suboptimal disease management, far too many
      patients with T1D have an increased risk for disease-associated complications
      such as nephropathy, neuropathy and retinopathy, as well as hypoglycaemia. New
      treatment modalities are therefore needed urgently to bring a 'true' cure
      (disease prevention/disease reversal) to patients with T1D. Here we consider
      issues that collectively pose a major stumbling block in T1D research with
      respect to identifying a means to prevent and/or cure the disease. We begin this
      Perspective by discussing new insights emanating from studies of the pancreas in
      human T1D; findings which may, at least in part, explain why previous
      interventions seeking disease prevention/reversal have yielded insufficient
      benefit. We then turn to suggestions that could optimise the outcome of future
      clinical trials. Finally, we direct attention to recommendations for the global
      T1D research community; messages we deem to have the potential to improve our
      chances of finding the elusive T1D 'cure'.

PMID- 25989478
TI  - Rapid COJEC versus standard induction therapies for high-risk neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is a rare malignant disease and mainly affects infants
      and very young children. The tumors mainly develop in the adrenal medullary
      tissue and an abdominal mass is the most common presentation. The high-risk group
      is characterized by metastasis and other characteristics that increase the risk
      for an adverse outcome. In the rapid COJEC induction schedule, higher single
      doses of selected drugs than standard induction schedules are administered over a
      substantially shorter treatment period, with shorter intervals between cycles.
      Shorter intervals and higher doses increase the dose intensity of chemotherapy
      and might improve survival. OBJECTIVES: The aim of this study was to evaluate the
      efficacy and adverse events of the rapid COJEC induction schedule as compared to
      standard induction schedules in patients with high-risk neuroblastoma (as defined
      by the International Neuroblastoma Risk Group (INRG) classification system).
      Outcomes of interest were complete response, early toxicity and treatment-related
      mortality as primary endpoints and overall survival, progression- and event-free
      survival, late non-hematological toxicity, and health-related quality of life as
      secondary endpoints. SEARCH METHODS: We searched the electronic databases CENTRAL
      (2014, Issue 11), MEDLINE (PubMed), and EMBASE (Ovid) for articles from inception
      to 11 November 2014. Further searches included trial registries, conference
      proceedings, and reference lists of recent reviews and relevant articles. We did
      not apply limits on publication year or languages. SELECTION CRITERIA: Randomized
      controlled trials evaluating the rapid COJEC induction schedule for high-risk
      neuroblastoma patients compared to standard induction schedules. DATA COLLECTION
      AND ANALYSIS: Two review authors performed study selection, abstracted data on
      study and patient characteristics, and assessed risk of bias independently. We
      resolved differences by discussion or by appeal to a third review author. We
      performed analyses according to the guidelines of the Cochrane Handbook for
      Systematic Reviews of Interventions. We used the five GRADE considerations, study
      limitations, consistency of effect, imprecision, indirectness, and publication
      bias, to judge the quality of the evidence. We downgraded for risk of bias and
      imprecision MAIN RESULTS: We identified one randomized controlled trial (CCLG
      ENSG-5) that included 262 patients with high-risk neuroblastoma who were
      randomized to receive either rapid COJEC (N = 130) or standard OPEC/COJEC (N =
      132) induction chemotherapy. We graded the evidence as low quality; we downgraded
      for risk of bias and imprecision.There was no clear evidence of a difference
      between the treatment groups in complete response (risk ratio (RR) 0.99, 95%
      confidence interval (CI) 0.71 to 1.38), treatment-related mortality (RR 1.21, 95%
      CI 0.33 to 4.39), overall survival (hazard ratio (HR) 0.83, 95% CI 0.63 to 1.10),
      and event-free survival (HR 0.86, 95% CI 0.65 to 1.13). We calculated the HRs
      using the complete follow-up period of the trial.Febrile neutropenia (two or more
      episodes), proven fungal infections, septicemia (one or more episodes),
      gastrointestinal toxicity (grade 3 or 4), renal toxicity (glomerular filtration
      rate < 80 ml/min per body surface area of 1.73 m(2)), neurological toxicity
      (grade 3 or 4), and ototoxicity (Brock grade 2 to 4) were addressed as early
      toxicities (during pre-operative chemotherapy). For febrile neutropenia,
      septicemia, and renal toxicity, a statistically significant difference in favor
      of the standard treatment arm was identified; for all other early toxicities no
      clear evidence of a difference between treatment groups was identified. With
      regard to late non-hematological toxicities (median follow-up 12.7 years; range
      6.9 to 16.5 years), the study provided data on any complication, renal toxicity
      (glomerular filtration rate < 80 ml/min per body surface area of 1.73m(2)),
      ototoxicity (Brock grade 1 to 4), endocrine complications, neurocognitive
      complications (i.e. behavioral, speech, or learning difficulties), and second
      malignancies. For endocrine complications and neurocognitive complications, a
      statistically significant difference in favor of the rapid COJEC arm was found;
      for all other late non-hematological toxicities no clear evidence of a difference
      between treatment groups was identified.Data on progression-free survival and
      health-related quality of life were not reported. AUTHORS' CONCLUSIONS: We
      identified one randomized controlled trial that evaluated rapid COJEC versus
      standard induction therapy in patients with high-risk neuroblastoma. No clear
      evidence of a difference in complete response, treatment-related mortality,
      overall survival, and event-free survival between the treatment alternatives was
      found. This could be the result of low power or too short a follow-up period.
      Results of both early and late toxicities were ambiguous. Information on
      progression-free survival and health-related quality of life were not available.
      This trial was performed in the 1990s. Since then, many changes in, for example,
      treatment and risk classification have occurred. Therefore, based on the
      currently available evidence, we are uncertain about the effects of rapid COJEC
      and standard induction therapy in patients with high-risk neuroblastoma. More
      research is needed for a definitive conclusion.

PMID- 25989479
TI  - What makes an allergen?
AB  - Allergic diseases are an immune disorder reacting to certain type of allergen(s).
      Remarkably only a small number of proteins of the plant and animal proteome act
      as allergens. Therefore, allergens have been clustered according to their common
      structural, biochemical and functional features. Evidence has accumulated that
      some allergens possess intrinsic adjuvant properties to stimulate the innate
      immunity. The adjuvant properties appear to contribute to the allergenicity of
      the respective proteins, namely the ability to cause allergic sensitization in
      susceptible subjects or allergic reactions in sensitized individuals. Here, we
      discuss how allergens interact with the innate immune cells, in particular
      dendritic cells and epithelial cells, via binding to pattern recognition
      receptors, exhibiting proteolytic activities and/or inducting type 2 innate
      lymphoid cells (ILC2), thereby contributing to the sensitization and development
      of allergic diseases.

PMID- 25989480
TI  - Evaluation of Low-Contrast Detectability of Iterative Reconstruction across
      Multiple Institutions, CT Scanner Manufacturers, and Radiation Exposure Levels.
AB  - PURPOSE: To compare image resolution from iterative reconstruction with
      resolution from filtered back projection for low-contrast objects on phantom
      computed tomographic (CT) images across vendors and exposure levels. MATERIALS
      AND METHODS: Randomized repeat scans of an American College of Radiology CT
      accreditation phantom (module 2, low contrast) were performed for multiple
      radiation exposures, vendors, and vendor iterative reconstruction algorithms.
      Eleven volunteers were presented with 900 images by using a custom-designed
      graphical user interface to perform a task created specifically for this reader
      study. Results were analyzed by using statistical graphics and analysis of
      variance. RESULTS: Across three vendors (blinded as A, B, and C) and across three
      exposure levels, the mean correct classification rate was higher for iterative
      reconstruction than filtered back projection (P < .01): 87.4% iterative
      reconstruction and 81.3% filtered back projection at 20 mGy, 70.3% iterative
      reconstruction and 63.9% filtered back projection at 12 mGy, and 61.0% iterative
      reconstruction and 56.4% filtered back projection at 7.2 mGy. There was a
      significant difference in mean correct classification rate between vendor B and
      the other two vendors. Across all exposure levels, images obtained by using
      vendor B's scanner outperformed the other vendors, with a mean correct
      classification rate of 74.4%, while the mean correct classification rate for
      vendors A and C was 68.1% and 68.3%, respectively. Across all readers, the mean
      correct classification rate for iterative reconstruction (73.0%) was higher
      compared with the mean correct classification rate for filtered back projection
      (67.0%). CONCLUSION: The potential exists to reduce radiation dose without
      compromising low-contrast detectability by using iterative reconstruction instead
      of filtered back projection. There is substantial variability across vendor
      reconstruction algorithms.

PMID- 25989481
TI  - Emerging role of long noncoding RNAs in autoimmune diseases.
AB  - Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new
      class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key
      role in the regulation of immunological functions and autoimmunity. Herein, we
      review the recent findings of lncRNA regulation in immune functions and in the
      development of autoimmunity and autoimmune disease. In addition, we focus on the
      involvement of lncRNA regulation in innate and adaptive immune responses, immune
      cell development, and differential expression of lncRNAs in autoimmune diseases,
      including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1
      diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease
      (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD).

PMID- 25989482
TI  - Effect of low frequency transcutaneous magnetic stimulation on sensory and motor
      transmission.
AB  - Peripheral nerve injury diminishes fast conducting large myelinated afferent
      fibers transmission but enhances smaller pain transmitting fibers firing. This
      aberrant afferent neuronal behavior contributes to development of chronic post
      traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic
      flux stimulation has been implicated in treating PTP-NP, a condition currently
      not adequately addressed by other therapies including transcutaneous electrical
      nerve stimulation (TENS). The current study assessed the effect of low frequency
      transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds,
      nerve conduction properties, and TENS induced fast afferent slowing effect as
      measured by motor and sensory conduction studies in the ulnar nerve. Results
      indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007,
      respectively) reduces sensory conduction velocity (CV) and increases sensory
      onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS
      (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P
      = 0.036) increases the sensory PL. LFTMS alone significantly (P < 0.05) elevates
      sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing
      effect on fast conducting fibers and casts a selective peripheral modulatory
      effect on slow conducting pain afferent fibers.

PMID- 25989483
TI  - Association of socioeconomic and practical unmet needs with self-reported
      nonadherence to cancer treatment appointments in low-income Latino and Black
      cancer patients.
AB  - OBJECTIVE: Treatment adherence, with minimal numbers of missed appointments, is
      an important determinant of survival among cancer patients. This study aims to
      determine if unmet financial, logistic, and supportive care needs predict self
      reported adherence to cancer treatment appointments of chemotherapy and/or
      radiation among low-income ethnic minority patients. DESIGN: The sample included
      1098 underserved Latino and Black patients recruited from cancer clinics in New
      York City through the Cancer Portal Project. Participants completed a survey
      which included sociodemographic, health-related questions and a needs assessment,
      in their preferred language. Patients' adherence to chemotherapy and/or radiation
      treatment appointments was assessed using a self-report. RESULTS: A sample of
      1098 patients (581 Latino and 517 Black cancer patients) was recruited. Forty-two
      Latino cancer patients (7.4%) and 78 Black cancer patients (15.5%) reported
      missing treatment appointments. Patients, who experienced four or more unmet
      needs (odds ratios [OR] = 2.02-3.36), and those with unmet housing needs (OR =
      3.10-3.31), were more likely to report missing cancer treatment appointments,
      regardless of their ethnicity/race. Black patients with unmet supportive care (OR
      = 2.27) and health insurance needs (OR = 3.80) were more likely to miss
      appointments. Amongst Latinos, legal health-related issues (OR = 2.51) was a
      significant predictor of missed appointments. CONCLUSIONS: Among ethnic minority
      cancer patients, unmet socioeconomic and supportive care needs, housing needs in
      particular, predicted patient-reported missed radiation, and/or chemotherapy
      appointments. Future research should focus on exploring the impact of practical
      and supportive unmet needs on adherence and development of interventions aiming
      to improve cancer treatment adherence.

PMID- 25989484
TI  - How does public opinion become extreme?
AB  - We investigate the emergence of extreme opinion trends in society by employing
      statistical physics modeling and analysis on polls that inquire about a wide
      range of issues such as religion, economics, politics, abortion, extramarital
      sex, books, movies, and electoral vote. The surveys lay out a clear indicator of
      the rise of extreme views. The precursor is a nonlinear relation between the
      fraction of individuals holding a certain extreme view and the fraction of
      individuals that includes also moderates, e.g., in politics, those who are "very
      conservative" versus "moderate to very conservative" ones. We propose an
      activation model of opinion dynamics with interaction rules based on the
      existence of individual "stubbornness" that mimics empirical observations.
      According to our modeling, the onset of nonlinearity can be associated to an
      abrupt bootstrap-percolation transition with cascades of extreme views through
      society. Therefore, it represents an early-warning signal to forecast the
      transition from moderate to extreme views. Moreover, by means of a phase diagram
      we can classify societies according to the percolative regime they belong to, in
      terms of critical fractions of extremists and people's ties. 

PMID- 25989485
TI  - Arts for health initiatives: an emerging international agenda and evidence base
      for older populations.

PMID- 25989486
TI  - Comment on: Higgins A., Sharek D., Nolan M., Sheerin B., Flanagan P.,
      Slaicuinaite S. & Walsh H. (2012) Mixed methods evaluation of an
      interdisciplinary sexuality education programme for staff working with people who
      have an acquired physical disability. Journal of Advanced Nursing 68(11), 238
      238.

PMID- 25989488
TI  - Writing locally, publishing globally: making papers 'international'.

PMID- 25989489
TI  - Philosophical ruminations on measurement: methodological orientations of patient
      reported outcome measures (PROMS).

PMID- 25989490
TI  - Effect of spinning workouts on affect.
AB  - BACKGROUND: Numerous physical exercises trigger positive changes in affect after
      relatively short workouts. Spinning, also known as indoor-cycling, is a very
      popular form of exercise, especially among women, but its impact on affect have
      not been examined to date. AIMS: The purpose of the current work was to
      investigate the possible benefits of spinning on affect in self-controlled and in
      instructor-led exercise sessions. METHODS: Using baseline measures and pre- to
      post-exercise design with a psychometrically validated questionnaire, the net
      effects of spinning (without music) on positive- and negative-affect were
      measured in two exercise conditions: (1) self-controlled workout (i.e. without an
      instructor) and (2) instructor-led workout. After both conditions, 18 women rated
      the extent which they enjoyed the exercise session on a 10-point Likert scale.
      RESULTS: The findings revealed that positive affect increased while negative
      affect decreased after both workouts. Exerted effort, measured through the heart
      rate, did not differ between the two conditions. However, participants enjoyed
      more the instructor-led exercise session than the self-regulated workout (effect
      size, Cohen's d = 0.93). CONCLUSIONS: This research reveals that spinning
      improves post-exercise affect, even without music and regardless of instructor's
      presence. Therefore, it demonstrates the net benefits of this popular exercise on
      affect.

PMID- 25989491
TI  - Difficulty describing feelings and post-traumatic symptoms after a collective
      trauma in survivors of L'Aquila earthquake.
AB  - BACKGROUND: The association between alexithymia and post-traumatic stress
      disorder (PTSD) symptoms has been demonstrated in several studies, but never in
      victims of a collective trauma such as a natural disaster, which has an impact on
      an entire community. AIMS: The aim was to assess the relationship between
      alexithymia and post-traumatic symptoms in a group of people who lived in
      L'Aquila exposed to the earthquake that hit the town in 2009. METHODS: Eighty
      seven participants were included and assessed for alexithymia, PTSD symptoms,
      depression, anxiety, and psychiatric symptoms. Linear regression models were used
      to test the hypothesis. RESULTS: The main finding was an association between
      "Difficulty-Describing-Feelings" and the intensity of post-traumatic symptoms in
      the worst month after trauma. Depression, anxiety and psychiatric comorbidity
      also showed a significant association with PTSD symptoms. CONCLUSIONS: In the
      present study of a collectively shared trauma, the alexithymic factor "difficulty
      describing-feelings" was significantly associated with the intensity of post
      traumatic symptoms.

PMID- 25989492
TI  - Spanish adaptation of the Revised Helping Alliance Questionnaire (HAq-II).
AB  - BACKGROUND: The working or helping alliance is one of the most widely studied
      constructs in psychotherapy process research. AIM: The aim of this study was to
      adapt the patient and therapist forms of the Revised Helping Alliance
      Questionnaire II (HAq-II-P and HAq-II-T, respectively) into Spanish. METHOD: The
      two measurement instruments were adapted through a systematic translation
      process, a pilot study and a clinical study. The psychometric properties were
      examined following the third psychotherapy session. RESULTS: Mean scores on the
      Spanish-language HAq-II-P and HAq-II-T were high. The corrected item-total
      correlations for >94% of the items were >0.30. Cronbach's alpha values for
      internal consistency were 0.88 and 0.93, respectively. Correlations for
      convergent validity with the respective versions of the Spanish-language Working
      Alliance Inventory were 0.80 and 0.87, respectively. In terms of predictive
      validity, there was a significant correlation between HAq-II-T and the patients'
      residual gain scores on the Spanish-language Beck Depression Inventory after the
      tenth psychotherapy session. CONCLUSIONS: These results are consistent with
      studies using the original English versions of the HAq-II.

PMID- 25989493
TI  - Hazardous alcohol use in general psychiatric outpatients.
AB  - BACKGROUND: Hazardous alcohol use in psychiatric patients may increase the risk
      of the development of a substance use disorder and negatively affect the course
      of the psychiatric disorder. AIMS: To investigate the prevalence of hazardous
      alcohol and drug use in a Swedish psychiatric outpatient population with
      particular focus on hazardous alcohol consumption and assess relationships of
      hazardous alcohol use to sex, age and psychiatric diagnosis. METHODS: General
      psychiatric outpatients, n = 1,679, completed a self-rating Alcohol Use Disorders
      Identification Test (AUDIT). RESULTS: Hazardous or harmful alcohol habits
      occurred among 22% of all women and 30% of all men with higher prevalence among
      younger patients. Nine percent of all women and 22 % of all men reported binge
      drinking. Binge drinking was more frequent in younger subjects. Women with a
      personality disorder diagnosis had a higher frequency of at risk drinking. Apart
      from that, psychiatric diagnosis was unrelated to rate of hazardous drinking.
      CONCLUSIONS: Hazardous alcohol use was common in this psychiatric outpatient
      population. With regard to possible risks related to drinking in psychiatric
      patients, alcohol habits should be assessed as a part of good clinical practice.

PMID- 25989498
TI  - Clinicopathological Findings of Chronic Rejection in a Face Grafted Patient.
AB  - BACKGROUND: Skin chronic rejection (CR) in vascularized composite
      allotransplantation has not been included in the Banff classification yet. We
      report a face-transplant patient who developed cutaneous clinicopathologic
      changes suggestive of CR. METHODS: The recipient was a 27-year-old man with
      severe disfigurement of the lower face due to a pyrotechnic explosion. He
      received a facial allograft, including mandible, cheeks, lips, and chin, in
      November 2009. Immunosuppression included antithymocyte globulins and bone-marrow
      infusion then steroids, tacrolimus, and mycophenolate mofetil. RESULTS: During
      the first posttransplant year the acute rejection episodes were characterized by
      reversible oedema and erythema of the graft. Subsequently, the patient developed
      primary asymptomatic Epstein-Barr virus (EBV) infection, followed by EBV+ B-cell
      lymphoma and hepatic EBV-associated posttransplant smooth muscle tumors;
      therefore, the immunosuppressive treatment was greatly reduced. Since the second
      posttransplant year, the allografted facial skin became progressively sclerotic
      and presented pigmented macules on a background of hypopigmentation and
      teleangiectasias, resulting in a poikilodermatous aspect. Skin biopsies showed
      epidermal atrophy, basal cell vacuolization, and diffuse dermal sclerosis in the
      absence of significant dermal cell infiltration. The dermal capillaries showed
      thickened walls and narrowed lumina, whereas the large vessels did not show
      significant alterations. Neither donor-specific antibodies nor vascular Cd4
      deposits were detected.A dysfunction of the graft functions occurred. It was
      evidenced by a decrease in mouth opening and modification of some phonemes
      although lip closure was still possible allowing food intake. CONCLUSIONS: This
      is the first report suggestive of CR in a face allotransplantation after
      immunosuppression minimization.

PMID- 25989497
TI  - Outcomes Following ABO-Incompatible Kidney Transplantation Performed After
      Desensitization by Nonantigen-Specific Immunoadsorption.
AB  - BACKGROUND: For desensitization of ABO-incompatible kidney transplant recipients
      we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab.
      METHODS: We now compared clinical outcomes of 34 ABO-incompatible living-donor
      kidney recipients who were transplanted using this protocol with that of 68
      matched ABO-compatible patients. In addition, we analyzed efficacy and cost of
      nonantigen-specific as compared to blood group antigen-specific IA. RESULTS:
      Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible
      patients was 1:64 (Coombs technique). Patients received a median of 7
      preoperative IA treatments. Twenty-four patients had a median of 2 additional
      plasmapheresis treatments to reach the preoperative target isoagglutinin titer of
      1:8 or less. After a median postoperative follow-up of 22 months, overall graft
      survival in the ABO-incompatible group was not significantly different from that
      in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended
      to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in
      both groups. The ABO-incompatible kidney recipients had a higher incidence of BK
      virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often
      colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood
      group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was
      associated with reduction in cost. CONCLUSIONS: Clinical outcomes of ABO
      incompatible patients desensitized with a nonantigen-specific IA device and
      rituximab do not differ from that of matched ABO-compatible patients although a
      trend toward reduced patient survival was noted. Special attention must be paid
      to the higher incidence of BK virus infection in recipients of ABO-incompatible
      grafts.

PMID- 25989499
TI  - Generation of Donor-specific T Regulatory Type 1 Cells From Patients on Dialysis
      for Cell Therapy After Kidney Transplantation.
AB  - BACKGROUND: T regulatory type 1 (Tr1) cell-mediated induction of tolerance in
      preclinical models of transplantation is remarkably effective. The clinical
      application of such a therapy in patients on dialysis undergoing kidney
      transplantation should take into account the possible alterations of the immune
      system observed in these patients. Herein, we aimed at testing the ability to
      generate donor-specific Tr1 cell-enriched lymphocytes from patients on dialysis
      on the waiting list for kidney transplantation. METHODS: The Tr1 cell-enriched
      lymphocytes were generated by coculturing interleukin-10-producing dendritic
      cells obtained from healthy donors with peripheral blood mononuclear cells
      (PBMCs) of patients on dialysis, following the same protocol used in a previous
      cell therapy clinical trial to prevent graft-versus-host disease. Alternatively,
      purified CD4(+) T cells were used instead of total PBMCs. The ability to generate
      clinical-grade Tr1 cell-enriched products was defined by testing the reduced
      response to restimulation with mature dendritic cells generated from the original
      donor (i.e., anergy assay). RESULTS: The Tr1 cell-enriched medicinal products
      generated from PBMCs of patients on dialysis showed a low anergic phenotype,
      incompatible with their eventual clinical application. This was irrespective of
      HLA matching with the donor or the intrinsically reduced ability to proliferate
      in response to alloantigens. On the contrary, the use of purified CD4(+) T cells
      isolated from patients on dialysis led to the generation of a highly anergic
      donor-specific medicinal product containing an average of 10% Tr1 cells.
      CONCLUSIONS: The Tr1 cell-enriched medicinal products can be efficiently
      generated from patients on dialysis by carefully tailoring the protocol on the
      patients' immunological characteristics.

PMID- 25989501
TI  - Patterns of Kidney Function Before and After Orthotopic Liver Transplant:
      Associations With Length of Hospital Stay, Progression to End-Stage Renal
      Disease, and Mortality.
AB  - BACKGROUND: In the context of orthotopic liver transplantation (OLT), renal
      dysfunction is used as a criterion for simultaneous liver-kidney transplantation.
      Changes in glomerular filtration rate (GFR) the year before and after OLT have
      not been well defined. METHODS: In a cohort of 416 OLT patients from 1996 to
      2009, estimated GFR (eGFR) was assessed during the 12 months before OLT (period
      A), at time of OLT (period B), and the 12 months after OLT (period C). Outcomes
      included progression to end stage renal disease (ESRD), length of stay, and
      mortality. RESULTS: The overall rate of progression to ESRD over 15 years of
      follow-up was 0.155/person-year and was strongly associated with eGFR <60 (hazard
      ratio [HR] = 2.7; P < 0.001), diabetes (HR = 2.6; P < 0.001), and with a
      combination of the 2 (HR = 5.5; P < 0.0001). Mean eGFR decreased from period A
      (86 mL/min per 1.73 m) to period B (77; P < 0.001) to period C (71; P < 0.001),
      with similar decreases in eGFR across subgroups of clinical variables. Patients
      with eGFR less than 60 mL/min per 1.73 m at OLT had acute and large decreases in
      eGFR from periods A to B, then increases to period C. Length of stay was
      associated with eGFR at OLT, hepatorenal syndrome, dialysis requirement, model
      for end-stage liver disease score, and alcoholic liver disease. Twelve-month
      mortality was strongly associated with time-dependent change in eGFR, hepatorenal
      syndrome, dialysis requirement, hepatitis C, and model for end-stage liver
      disease era transplantation but was not associated with eGFR at OLT. CONCLUSIONS:
      Among OLT patients, renal function worsened in all subgroups from before to after
      OLT, but the association of progression to ESRD was particularly high among
      patients with both diabetes and eGFR less than 60 at the time of OLT. This
      suggests that diabetes could be considered as a criterion when making decisions
      regarding simultaneous liver-kidney transplantation.

PMID- 25989500
TI  - Stimulation of Dopamine D3 Receptor Attenuates Renal Ischemia-Reperfusion Injury
      via Increased Linkage With Galpha12.
AB  - BACKGROUND: Renal ischemia-reperfusion (I/R) injury causes renal tubular
      necrosis, apoptosis, and inflammation leading to acute renal dysfunction. Recent
      studies have revealed that deletion of Galpha12 mitigates the renal damage due to
      I/R injury. Our previous study showed that activation of dopamine D3 receptor
      (D3R) increased its linkage with Galpha12, and hampered Galpha12-mediated
      stimulation of renal sodium transport. In the present study, we used an in-vivo
      rat model and an in vitro study of the renal epithelial cell line (NRK52E) to
      investigate whether or not an increased linkage between D3R and Galpha12
      contributes to the protective effect of D3R on renal I/R injury. METHODS: For in
      vivo studies, I/R injury was induced in a rat renal unilateral clamping model.
      For in vitro studies, hypoxia/reoxygenation and cold storage/rewarming injuries
      were performed in NRK52E cells. PD128907, a D3R agonist, or vehicle, was
      administered 15 minutes before clamping (or hypoxia) in both the in vivo or in
      vitro studies. RESULTS: In the rat renal unilateral clamping model, pretreatment
      with PD128907 (0.2 mg/kg, intravenous) protected against renal I/R injury and
      increased survival rate during a long-term follow-up after 7 days. A decrease in
      the generation of reactive oxygen species, apoptosis, and inflammation may be
      involved in the D3R-mediated protection because pretreatment with PD128907
      increased renal glutathione and superoxide dismutase levels and decreased
      malondialdehyde levels in the I/R group. The increase in cytokines (TNF-alpha, IL
      1beta, and IL-10) and myeloperoxidase in I/R injured kidney was also prevented
      with a simultaneous decrease in the apoptosis of the epithelial cells and
      expression of apoptosis biomarkers in kidney harvested 1 day after I/R injury.
      The increase in the coimmunoprecipitation between D3R and Galpha12 with D3R
      stimulation paralleled the observed renal protection from I/R injury. Moreover,
      in vitro studies showed that transient overexpression of Galpha12 in the NRK52E
      cells attenuated the protective effect of PD128907 on hypoxia/reoxygenation
      injury. The protective effect of PD128907 might be of significance to renal
      transplantation because cold storage/rewarming induced injury increased lactate
      dehydrogenase release and decreased cell viability in NRK52E cells. Conversely,
      in the presence of PD128907, the increased lactate dehydrogenase release and
      decreased cell viability were reversed. CONCLUSIONS: These results suggest that
      activation of D3R, by decreasing Galpha12-induced renal damage, may exert a
      protective effect from I/R injury.

PMID- 25989502
TI  - Spontaneous Splenorenal Shunt in Liver Transplantation: Results of Left Renal
      Vein Ligation Versus Renoportal Anastomosis.
AB  - BACKGROUND: Management of portal inflow to the graft in patients with spontaneous
      splenorenal shunts (SRS) is a matter of concern especially in case of large
      varices (more than 1 cm). In case of portal vein (PV) thrombosis (PVT),
      renoportal anastomosis (RPA) directly diverts the splanchnic and renal venous
      blood assuring a good portal inflow to the graft. Disconnection of the portacaval
      shunt by left renal vein ligation (LRVL) is another option but requires a patent
      PV. The indication of primary RPA rather than LRVL in patients with small native
      PV, especially in case of large graft, should be questioned in these complex
      cases of liver transplantation. METHODS: From 1998 to 2012, 17 patients with RPA
      and 15 patients with LRVL were transplanted in our center. We compared these 2
      techniques for short- and long-term results. RESULTS: The rate of preliver
      transplantation PVT (76% vs 27%) and graft weight (1538 +/- 383 g vs 1293 +/- 216
      g) was significantly higher in the RPA group. Renoportal anastomosis was
      performed in 4 cases of small but patent PV. Three-month mortality, morbidity,
      and massive ascitis were similar. No patient was retransplanted. One year after
      transplantation, PV diameter was still larger in RPA group. Three-year survival
      was similar (RPA: 79% vs LRVL: 53%, P = 0.1). CONCLUSIONS: In cirrhotic patients
      transplanted with large splenorenal shunts, RPA and LRVL reach similar survivals.
      In case of complete PVT and failure of thrombectomy, the RPA offers satisfactory
      long-term results.

PMID- 25989503
TI  - Variable Use of Model for End-Stage Liver Disease Exception Points in Patients
      With Neuroendocrine Tumors Metastatic to the Liver and Its Impact on Patient
      Outcomes.
AB  - BACKGROUND: The role of liver transplantation in management of patients with
      metastatic neuroendocrine tumors (NETs) is controversial. Because many such
      patients have low waitlist priority, centers may apply for model for end-stage
      liver disease (MELD) exception points to increase likelihood of receiving a liver
      transplant. No formal criteria exist for application or receipt of exception
      points for this indication. Few studies have assessed waitlist and
      posttransplantation outcomes in patients with metastatic NETs, and none examined
      the impact of exception points. METHODS: We analyzed all adult patients
      waitlisted for liver transplantation for metastatic NETs between February 27,
      2002, and June 4, 2014, and fit a multivariable model to evaluate the association
      between exception point status and posttransplantation outcomes. RESULTS: There
      was variable use of MELD exception points across the United Network for Organ
      Sharing regions. Patients with an approved MELD exception were nearly twice as
      likely to be transplanted as those without exceptions (70.8% vs 39.1%, P <
      0.001), and half as likely to be removed for death or clinical deterioration
      (9.2% vs 18.2%, P = 0.046). In multivariable models, posttransplantation survival
      was not associated with receipt of exception points, whereas risk of
      posttransplant mortality increased significantly with elevated serum total
      bilirubin level at transplantation. The 3-year posttransplant patient survival
      was 78% in transplant recipients with metastatic NETs whose total bilirubin level
      at transplantation was 1.3 mg/dL or less, compared to 36% in those with total
      bilirubin greater than 1.3 mg/dL. CONCLUSIONS: Serum total bilirubin may serve as
      a predictor of poor posttransplant survival in patients with metastatic NETs and
      could help risk-stratify patients applying for MELD exception points.

PMID- 25989504
TI  - Von Willebrand Factor Deficiency Corrected by Lung Transplantation.
AB  - BACKGROUND: In experimental models with von Willebrand disease pigs, plasma von
      Willebrand factor (vWF) was significantly increased after lung transplantation
      because lung endothelial cells strongly express vWF. However, these findings have
      not been confirmed in human beings. METHODS: A 26-year-old man with mild vWF
      deficiency (FvW:antigen 39 IU/dL; FvW:ristocetin cofactor activity 44 IU/dL;
      factor VIII 99%; normal multimeric plasma vWF pattern) was referred to our
      institution and underwent bilateral lung transplantation for cystic fibrosis. The
      patient received factor VIII/vWF concentrate both during and after surgery
      without any relevant bleeding events. At hospital discharge, he was taking
      immunosuppression with oral tacrolimus, prednisone, and mycophenolate mofetil,
      which has continued until the present day (22 months after the procedure).
      RESULTS: Plasma vWF level increased during the postoperative days, presumably due
      to endothelial injuries and the infusion of vWF concentrate. Laboratory tests at
      5, 11, 14, and 22 months after lung transplantation demonstrated sustained
      normalization of all parameters. CONCLUSIONS: To our knowledge, this is the first
      reported case of von Willebrand deficiency corrected through lung
      transplantation.

PMID- 25989505
TI  - Down syndrome: Cognitive and behavioral functioning across the lifespan.
AB  - Individuals with Down syndrome (DS) commonly possess unique neurocognitive and
      neurobehavioral profiles that emerge within specific developmental periods. These
      profiles are distinct relative to others with similar intellectual disability
      (ID) and reflect underlying neuroanatomic findings, providing support for a
      distinctive phenotypic profile. This review updates what is known about the
      cognitive and behavioral phenotypes associated with DS across the lifespan. In
      early childhood, mild deviations from neurotypically developing trajectories
      emerge. By school-age, delays become pronounced. Nonverbal skills remain on
      trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal
      learning and memory are strengths relative to verbal skills. Expressive language
      is delayed relative to comprehension. Aspects of language skills continue to
      develop throughout adolescence, although language skills remain compromised in
      adulthood. Deficits in attention/executive functions are present in childhood and
      become more pronounced with age. Characteristic features associated with DS
      (cheerful, social nature) are personality assets. Children are at a lower risk
      for psychopathology compared to other children with ID; families report lower
      levels of stress and a more positive outlook. In youth, externalizing behaviors
      may be problematic, whereas a shift toward internalizing behaviors emerges with
      maturity. Changes in emotional/behavioral functioning in adulthood are typically
      associated with neurodegeneration and individuals with DS are higher risk for
      dementia of the Alzheimer's type. Individuals with DS possess many unique
      strengths and weaknesses that should be appreciated as they develop across the
      lifespan. Awareness of this profile by professionals and caregivers can promote
      early detection and support cognitive and behavioral development.

PMID- 25989507
TI  - Genomic analysis of a ginger pathogen Bacillus pumilus providing the
      understanding to the pathogenesis and the novel control strategy.
AB  - Bacillus pumilus has been widely identified as a pathogen of plant and human,
      while the genetic information is rarely available for pathogenic B. pumilus
      strains. B. pumilus GR8 is a pathogen that causes ginger rhizome rot disease by
      invading ginger rhizome parenchymatous tissues, growing in the extracellular
      space, and producing plant cell wall-degrading enzymes to destroy ginger cells.
      In this study, the genome of GR8 was sequenced and characterized. This genome was
      the third completely sequenced genome of the B. pumilus species, and it exhibited
      high similarity to the genome of the B. pumilus strain B6033. The genome of GR8
      was 3.67 Mb in length and encoded 3,713 putative ORFs. Among these predicted
      proteins, numerous plant cell wall-degrading enzymes and several proteins
      associated with invading and adapting to the environment in the extracellular
      space of the ginger rhizome parenchymatous tissue were found. The GR8 genome
      contained only one restriction-modification system and no CRISPR/Cas system. The
      lack of phage-resistant system suggested that phages might be potential agents
      for the control of GR8. The genomic analysis of GR8 provided the understanding to
      the pathogenesis and the phage-control strategy of pathogenic B. pumilus strains.

PMID- 25989506
TI  - The BRAF(V600E) inhibitor, PLX4032, increases type I collagen synthesis in
      melanoma cells.
AB  - Vertical growth phase (VGP) melanoma is frequently metastatic, a process mediated
      by changes in gene expression, which are directed by signal transduction pathways
      in the tumor cells. A prominent signaling pathway is the Ras-Raf-Mek-Erk MAPK
      pathway, which increases expression of genes that promote melanoma progression.
      Many melanomas harbor a mutation in this pathway, BRAF(V600E), which
      constitutively activates MAPK signaling and expression of downstream target genes
      that facilitate tumor progression. In BRAF(V600E) melanoma, the small molecule
      inhibitor, vemurafenib (PLX4032), has revolutionized therapy for melanoma by
      inducing rapid tumor regression. This compound down-regulates the expression of
      many genes. However, in this study, we document that blocking the Ras-Raf-Mek-Erk
      MAPK pathway, either with an ERK (PLX4032) or a MEK (U1026) signaling inhibitor,
      in BRAF(V600E) human and murine melanoma cell lines increases collagen synthesis
      in vitro and collagen deposition in vivo. Since TGFbeta signaling is a major
      mediator of collagen synthesis, we examined whether blocking TGFbeta signaling
      with a small molecule inhibitor would block this increase in collagen. However,
      there was minimal reduction in collagen synthesis in response to blocking TGFbeta
      signaling, suggesting additional mechanism(s), which may include activation of
      the p38 MAPK pathway. Presently, it is unclear whether this increased collagen
      synthesis and deposition in melanomas represent a therapeutic benefit or an
      unwanted "off target" effect of inhibiting the Ras-Raf-Erk-Mek pathway. 

PMID- 25989508
TI  - Effect of human umbilical cord blood derived lineage negative stem cells
      transplanted in amyloid-beta induced cognitive impaired mice.
AB  - Alzheimer's disease (AD) is pathologically characterized by extracellular
      deposition of insoluble amyloid-beta (Abeta) plaques and intracellular tangles
      made up of phosphorylated tau in brain. Several therapeutic approaches are being
      carried out in animal AD models for testing their safety and efficacy in altering
      disease pathology and behavioral deficits. Very few studies have examined the
      effect of human umbilical cord blood (hUCB) derived stem cells in degenerative
      disease models despite growing number of cord blood banks worldwide. Here we have
      examined the therapeutic efficacy of hUCB derived lineage negative (Lin -ve) stem
      cells in alleviating behavioral and neuropathological deficits in a mouse model
      of cognitive impairment induced by bilateral intrahippocampal injection of Abeta
      42. Lin -ve cells were transplanted at two doses (50,000 and 100,000) at the site
      of injury and examined at 10 and 60 days post transplantation for rescue of
      memory deficits. These cells were found to ameliorate cognitive impairment in
      50,000-60 days and 100,000-10 days groups whereas, 50,000-10 days and 100,000-60
      days groups could not exert any significant improvement. Further, mice showing
      spatial memory improvement were mediated by up-regulation of BDNF, CREB and also
      by concomitant down regulation of Fas-L in their brain. The transplanted cells
      were found in the host tissue and survived up to 60 days without expressing
      markers of neuronal differentiation or reducing Abeta burden in mouse brain. We
      suggest that these undifferentiated cells could exert neuroprotective effects
      either through inhibiting apoptosis and/or trophic effects in the brain. 

PMID- 25989509
TI  - Head-To-Head Comparison of Different Solubility-Enabling Formulations of
      Etoposide and Their Consequent Solubility-Permeability Interplay.
AB  - The purpose of this study was to conduct a head-to-head comparison of different
      solubility-enabling formulations, and their consequent solubility-permeability
      interplay. The low-solubility anticancer drug etoposide was formulated in several
      strengths of four solubility-enabling formulations: hydroxypropyl-beta
      cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant
      sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability
      of these formulations to increase the solubility of etoposide was investigated,
      followed by permeability studies using the parallel artificial membrane
      permeability assay (PAMPA) and examination of the consequent solubility
      permeability interplay. All formulations significantly increased etoposide's
      apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based
      formulations resulted in a concomitant decreased permeability that could be
      modeled directly from the proportional increase in the apparent solubility. On
      the contrary, etoposide permeability remained constant when using the ASD
      formulation, irrespective of the increased apparent solubility provided by the
      formulation. In conclusion, supersaturation resulting from the amorphous form
      overcomes the solubility-permeability tradeoff associated with other formulation
      techniques. Accounting for the solubility-permeability interplay may allow to
      develop better solubility-enabling formulations, thereby maximizing the overall
      absorption of lipophilic orally administered drugs.

PMID- 25989511
TI  - Disentangling trait-based mortality in species with decoupled size and age.
AB  - 1. Size and age are fundamental organismal traits, and typically, both are good
      predictors of mortality. For many species, however, size and age predict
      mortality in ontogenetically opposing directions. Specifically, mortality due to
      predation is often more intense on smaller individuals whereas mortality due to
      senescence impacts, by definition, on older individuals. 2. When size-based and
      age-based mortality are independent in this manner, modelling mortality in both
      traits is often necessary. Classical approaches, such as Leslie or Lefkovitch
      matrices, usually require the model to infer the state of one trait from the
      state of the other, for example by assuming that explicitly modelled age (or
      stage) class structure provides implicit information on underlying size-class
      structure, as is the case in many species. 3. However, the assumption that one
      trait informs on the other is challenged when size and age are decoupled, as
      often occurs in invertebrates, amphibians, fish, reptiles and plants. In these
      cases, age-structured models may perform poorly at capturing size-based
      mortality, and vice versa. 4. We offer a solution to this dilemma, relaxing the
      assumption that class structure in one trait is inferable from class structure in
      another trait. Using empirical data from a reef fish, Sparisoma viride
      (Scaridae), we demonstrate how an individual-based model (IBM) can be implemented
      to model mortality as explicit, independent and simultaneous functions of
      individual size and age - an approach that mimics the effects of mortality in
      many wild populations. By validating this 'multitrait IBM' against three
      independent lines of empirical data, we determine that the approach produces more
      convincing predictions of size-class structure, longevity and post-settlement
      mortality for S. viride than do the trait-independent or single-trait mortality
      models tested. 5. Multitrait IBMs also allow trait-based mortality to be modelled
      either additively or multiplicatively, and individual variability in growth rates
      can be accommodated. Consequently, we propose that the approach may be useful in
      fields that may benefit from disentangling, or investigating interactions among,
      size-based and age-based demographic processes, including comparative demography
      (e.g. life-history consequences of resource patchiness) and conservation biology
      (e.g. impacts of invasive predators on size structure but not life span of
      natives).

PMID- 25989510
TI  - Estimating True Resource Costs of Outpatient Care for Medicare Beneficiaries:
      Standardized Costs versus Medicare Payments and Charges.
AB  - OBJECTIVE: To compare standardized estimates of the true resource costs of
      outpatient health care to the allowable and billed charges for that care among
      Medicare Fee for Service (FFS) beneficiaries. DATA SOURCES/STUDY SETTING:
      Medicare Carrier and Outpatient Standard Analytic (SAF) files linked to
      participant data in the Study of Osteoporotic Fractures from 2004 through 2010.
      Participants were 3,435 female Medicare Fee for Service enrollees age 80 and
      older recruited in one rural and three metropolitan areas of the United States.
      STUDY DESIGN: We estimated standardized costs for Carrier and OP-SAF claims using
      Medicare payment weights, and compared them to allowable and billed charges for
      those claims. We used semilog linear regression to estimate the associations of
      age, race, bone mineral density, prior fracture, and geriatric depression scale
      score with allowable charges, billed charges, and standardized costs. RESULTS:
      Estimated associations of patient characteristics with standardized costs were
      not statistically different than the associations with allowable charges (chi
      squared [chi(2)]: 8.6, p = .13) but were different from associations with billed
      charges (chi(2): 25.5, p < .001). CONCLUSION: Allowable charges for outpatient
      utilization in the Carrier file and OP-SAF may be good surrogates for
      standardized costs that reflect patient medical and surgical acuity.

PMID- 25989512
TI  - REPLY TO LETTERS.

PMID- 25989513
TI  - Mussel-Inspired Electrospun Nanofibers Functionalized with Size-Controlled Silver
      Nanoparticles for Wound Dressing Application.
AB  - Electrospun nanofibers that contain silver nanoparticles (AgNPs) have a strong
      antibacterial activity that is beneficial to wound healing. However, most of the
      literature available on the bactericidal effects of this material is based on the
      use of AgNPs with uncontrolled size, shape, surface properties, and degree of
      aggregation. In this study, we report the first versatile synthesis of novel
      catechol moieties presenting electrospun nanofibers functionalized with AgNPs
      through catechol redox chemistry. The synthetic strategy allows control of the
      size and amount of AgNPs on the surface of nanofibers with the minimum degree of
      aggregation. We also evaluated the rate of release of the AgNPs, the
      biocompatibility of the nanofibers, the antibacterial activity in vitro, and the
      wound healing capacity in vivo. Our results suggest that these silver-releasing
      nanofibers have great potential for use in wound healing applications. 

PMID- 25989514
TI  - Elucidating the Sorption Mechanism of Dibromomethane in Disordered Mesoporous
      Silica Adsorbents.
AB  - The mechanism of dibromomethane (DBM) sorption in mesoporous silica was
      investigated by in situ small-angle X-ray scattering (SAXS). Six different
      samples of commercial porous silica particles used for liquid chromatography were
      studied, featuring a disordered mesoporous structure, with some of the samples
      being functionalized with alkyl chains. SAXS curves were recorded at room
      temperature at various relative pressures P/P0 during adsorption of DBM. The in
      situ SAXS experiment is based on contrast matching between silica and condensed
      DBM with regard to X-ray scattering. One alkyl-modified silica sample was
      evaluated in detail by extraction of the chord-length distribution (CLD) from
      SAXS data obtained for several P/P0. On the basis of this analytical approach and
      by comparison with ex situ obtained data of nitrogen and DBM adsorption, the
      mechanism of DBM uptake was studied. Results of average mesopore sizes obtained
      with the CLD method were compared with pore size analysis using nitrogen
      physisorption (77 K) with advanced state-of-the-art nonlocal density functional
      theory (NLDFT) evaluation. The dual SAXS/physisorption study indicates that
      microporosity is negligible in all silica samples and that surface
      functionalization with a hydrophobic ligand has a major influence upon the
      process of DBM adsorption. Also, all of the mesopores are accessible as evidenced
      by in situ SAXS. The data suggest that no multilayer adsorption occurs on C18
      (octadecyl-)modified silica surfaces using DBM as adsorptive, and it is possibly
      also negligible on bare silica surfaces. 

PMID- 25989515
TI  - Structure and dynamics of metallic and carburized catalytic Ni nanoparticles:
      effects on growth of single-walled carbon nanotubes.
AB  - Understanding the evolution of the catalyst structure and interactions with the
      nascent nanotube under typical chemical vapor deposition (CVD) conditions for the
      synthesis of single-walled carbon nanotubes is an essential step to discover a
      way to guide growth toward desired chiralities. We use density functional theory
      (DFT) and ab initio molecular dynamics (AIMD) simulations on model metallic and
      carburized Ni clusters to explore changes in the fundamental features of the
      nanocatalyst: geometric and electronic structure, dynamics and stability of the
      carburized nanocatalyst, and interactions with nascent nanotube caps at two
      different temperatures (750 and 1000 K) and different carbon composition ratios.
      This allows us to gain insight about the evolution of these aspects during the
      pre-growth and growth stages of CVD synthesis of single-walled carbon nanotubes
      and their implications for reactivity and control of the nanotube structure. 

PMID- 25989518
TI  - The Effects of Phellinus linteus Polysaccharide Extracts on Cholesterol Efflux in
      Oxidized Low-Density Lipoprotein-Loaded THP-1 Macrophages.
AB  - The removal of excess cellular cholesterol is critical for maintaining cellular
      cholesterol homeostasis. Phellinus linteus polysaccharide extracts (PLPEs) is an
      immunomudulatory agent with a molecular weight of 153 kd. Here, we analyzed the
      effects of PLPEs on cholesterol efflux in oxidized low-density lipoprotein (ox
      LDL)-loaded THP-1 (human acute monocytic leukemia cell line) macrophages. Various
      concentrations of PLPEs (5, 10, 20, and 100 MUg/mL) were used to treat cells.
      Cholesterol efflux analysis was performed to analyze the cholesterol efflux ratio
      in PLPE-treated cells. Semiquantitative reverse transcription-polymerase chain
      reaction and Western blot analysis were conducted to assess the expression of
      target genes. Low dose of PLPEs (5-20 MUg/mL) dose dependently enhanced
      cholesterol efflux to apolipoprotein A-I (ApoA-I), evidenced by promoting the
      expression of adenosine 5'-triphosphate (ATP)-binding cassette A1, ATP-binding
      cassette G1, and peroxisome proliferation-activated receptor gamma, key
      regulators for cholesterol efflux. Moreover, GW9662, a potent antagonist of
      peroxisome proliferation-activated receptor gamma, inhibited PLPE (20 MUg/mL)
      promoted cholesterol efflux to ApoA-I in a dose-dependent fashion. However, high
      dose of PLPEs (100 MUg/mL) inhibited cholesterol efflux to ApoA-I from ox-LDL
      loaded THP-1 macrophages, enhanced the production of superoxide anion, decreased
      mitochondrial membrane potential and ATP levels, and raised nicotinamide adenine
      dinucleotide/nicotinamide adenine dinucleotide phosphate oxidase subunits. Thus,
      these results indicate that low and high doses of PLPEs exhibit opposite effects
      on cholesterol efflux from ox-LDL-loaded THP-1 cells. 

PMID- 25989520
TI  - Nitrate denitrification with nitrite or nitrous oxide as intermediate products:
      Stoichiometry, kinetics and dynamics of stable isotope signatures.
AB  - A kinetic analysis of nitrate denitrification by a single or two species of
      denitrifying bacteria with glucose or ethanol as a carbon source and nitrite or
      nitrous oxide as intermediate products was performed using experimental data
      published earlier (Menyailo and Hungate, 2006; Vidal-Gavilan et al., 2013).
      Modified Monod kinetics was used in the dynamic biological model. The special
      equations were added to the common dynamic biological model to describe how
      isotopic fractionation between N species changes. In contrast to the generally
      assumed first-order kinetics, in this paper, the traditional Rayleigh equation
      describing stable nitrogen and oxygen isotope fractionation in nitrate was
      derived from the dynamic isotopic equations for any type of kinetics. In
      accordance with the model, in Vidal-Gavilan's experiments, the maximum specific
      rate of nitrate reduction was proved to be less for ethanol compared to glucose.
      Conversely, the maximum specific rate of nitrite reduction was proved to be much
      less for glucose compared to ethanol. Thus, the intermediate nitrite
      concentration was negligible for the ethanol experiment, while it was significant
      for the glucose experiment. In Menyailo's and Hungate's experiments, the low
      value of maximum specific rate of nitrous oxide reduction gives high intermediate
      value of nitrous oxide concentration. The model showed that the dynamics of
      nitrogen and oxygen isotope signatures are responding to the biological dynamics.
      Two microbial species instead of single denitrifying bacteria are proved to be
      more adequate to describe the total process of nitrate denitrification to
      dinitrogen. 

PMID- 25989521
TI  - Retrospective monitoring of mercury in fish from selected European freshwater and
      estuary sites.
AB  - Levels and trends of total mercury (THg) and methylmercury (MeHg) compounds in
      bream (Abramis brama) from different European sites were compared. Bream were
      collected between 2007 and 2013 in the estuaries of the rivers Scheldt
      (Netherlands), Rhone (France), Gota alv (Sweden), Tees (United Kingdom), and
      Mersey (UK), and in Lake Belau (Germany). A direct mercury analyzer was used to
      determine THg concentrations while MeHg was measured by gas
      chromatography/inductively coupled plasma-mass spectrometry applying stable
      isotope dilution. THg and MeHg in annual pool samples of bream ranged between
      15.9 and 251 MUg kg(-1) wet weight (ww) with lowest concentrations found at the
      reference site Lake Belau and highest in samples from the river Rhone. The EU
      environmental quality standard (EQS) of 20 MUg kg(-1) ww was exceeded at all
      sites and in all years except at Lake Belau in 2012. Significantly decreasing
      trends over time were observed only in bream from the Rhone, while THg increased
      in bream from the Western Scheldt. The MeHg fractions of THg were always >80% and
      a significant difference between sites was detected only in one case (Rhone vs.
      Lake Belau).

PMID- 25989522
TI  - Residual perfluorochemicals in the biochar from sewage sludge.
AB  - Biochar has been recently considered as a candidate for soil amendment and soil
      remediation. Some pollutants have been screened in the biochar for safety
      purposes except for perfluorochemicals (PFCs). In this study, the contamination
      of biochars from plant residues and sewage sludge with perfluorooctanesulfonic
      acid (PFOS) and perfluorooctanoic acid (PFOA) was examined. The total residual
      concentrations of PFOA and PFOS in the sludge biochar were 15.8-16.9 ng/g and
      these values did not decrease significantly after pyrolysis. On the other hand,
      these PFCs were not found in the biochar from plant sources. In conclusion, the
      use of the sludge biochar in the agricultural environment should be re-evaluated,
      since the concentrations of PFCs in the sewage sludge showed no significant
      decrease after thermal process.

PMID- 25989523
TI  - Atrazine immobilization on sludge derived biochar and the interactive influence
      of coexisting Pb(II) or Cr(VI) ions.
AB  - Sludge derived biochars (SDBCs) may have the potential to simultaneously remove
      heavy metals and organic contaminants in relation to their various active
      sorption sites for both metal ions and organic compounds. SDBCs have been proven
      to provide a considerable capacity for immobilizing Pb(II) and Cr(VI) ions in
      solution, and in this study their ability to sorb atrazine, in addition to their
      corresponding interactive influences with coexisting metal ions, is extensively
      investigated. The results indicate that all atrazine adsorption isotherms fit
      well with the Freundlich equation, and the greatest value of 16.8 mg g(-1)
      sorption capacity occurred with SDBCs pyrolyzed at 400 degrees C for 2h. The slow
      sorption kinetics fit well with the Lagergren's 2nd order reaction, and depend
      upon the initial atrazine concentration, indicating the significance of a site
      specific process. The ionic strength-dependence of the atrazine adsorption
      behavior further consolidates the involvement of the mechanism of the H-bond with
      hydroxyl groups on SDBC. However, when Pb(II)/Cr(VI) metal ions coexist in
      solution, they substantially suppress atrazine adsorption, probably because the
      inner complex between the hydroxyl groups on SDBCs and Pb(II)/Cr(III) ions
      intrude the weak H-bond with atrazine. As a result, metal adsorption was found to
      be unaffected by the coexisting atrazine. Therefore, although SDBC is applicable
      for atrazine removal/immobilization in most of environmentally relevant
      conditions, a two-step process may be required if heavy metal ions coexist.

PMID- 25989524
TI  - In vivo two-photon imaging of axonal dieback, blood flow, and calcium influx with
      methylprednisolone therapy after spinal cord injury.
AB  - Severe spinal cord injury (SCI) can cause neurological dysfunction and paralysis.
      However, the early dynamic changes of neurons and their surrounding environment
      after SCI are poorly understood. Although methylprednisolone (MP) is currently
      the standard therapeutic agent for treating SCI, its efficacy remains
      controversial. The purpose of this project was to investigate the early dynamic
      changes and MP's efficacy on axonal damage, blood flow, and calcium influx into
      axons in a mouse SCI model. YFP H-line and Thy1-GCaMP transgenic mice were used
      in this study. Two-photon microscopy was used for imaging of axonal dieback,
      blood flow, and calcium influx post-injury. We found that MP treatment attenuated
      progressive damage of axons, increased blood flow, and reduced calcium influx
      post-injury. Furthermore, microglia/macrophages accumulated in the lesion site
      after SCI and expressed the proinflammatory mediators iNOS, MCP-1 and IL-1beta.
      MP treatment markedly inhibited the accumulation of microglia/macrophages and
      reduced the expression of the proinflammatory mediators. MP treatment also
      improved the recovery of behavioral function post-injury. These findings suggest
      that MP exerts a neuroprotective effect on SCI treatment by attenuating
      progressive damage of axons, increasing blood flow, reducing calcium influx, and
      inhibiting the accumulation of microglia/macrophages after SCI. 

PMID- 25989525
TI  - Cost-effectiveness of Chlamydia vaccination programs for young women.
AB  - We explored potential cost-effectiveness of a chlamydia vaccine for young women
      in the United States by using a compartmental heterosexual transmission model. We
      tracked health outcomes (acute infections and sequelae measured in quality
      adjusted life-years [QALYs]) and determined incremental cost-effectiveness ratios
      (ICERs) over a 50-year analytic horizon. We assessed vaccination of 14-year-old
      girls and catch-up vaccination for 15-24-year-old women in the context of an
      existing chlamydia screening program and assumed 2 prevaccination prevalences of
      3.2% by main analysis and 3.7% by additional analysis. Estimated ICERs of
      vaccinating 14-year-old girls were $35,300/QALY by main analysis and $16,200/QALY
      by additional analysis compared with only screening. Catch-up vaccination for 15
      24-year-old women resulted in estimated ICERs of $53,200/QALY by main analysis
      and $26,300/QALY by additional analysis. The ICER was most sensitive to
      prevaccination prevalence for women, followed by cost of vaccination, duration of
      vaccine-conferred immunity, and vaccine efficacy. Our results suggest that a
      successful chlamydia vaccine could be cost-effective. 

PMID- 25989526
TI  - Soft Tissue Sarcoma With Tongue Metastasis: A Case Report and Literature Review.
AB  - Soft tissue sarcomas are rare malignant tumors that develop from mesenchymal
      cells. Metastasis is predominantly hematologic, with the lungs being the most
      common site. Metastasis to the oral cavity is a rare occurrence. The most common
      primary tumors to metastasize to the oral cavity are adenocarcinoma of the lung,
      breast, and kidney. This report describes a case of a 41-year-old man who was
      diagnosed with myxofibrosarcoma of the lower extremity and underwent neoadjuvant
      chemoradiation followed by surgical resection. Two years later, he presented with
      metastasis to the tongue and lungs. The literature on tongue metastasis of soft
      tissue sarcoma is reviewed and discussed. Surgeons providing care to patients
      with a soft tissue sarcoma should maintain a strong clinical suspicion for
      distant metastases in patients with this type of tumor. 

PMID- 25989528
TI  - A method of continuous indirect aspiration for field clearance in lymphatic
      supermicrosurgery.

PMID- 25989527
TI  - Resonance Frequency Analysis of Sinus Augmentation by Osteotome Sinus Floor
      Elevation and Lateral Window Technique.
AB  - PURPOSE: To evaluate the use of resonance frequency analysis (RFA) to
      quantitatively compare the stability of implants placed in the atrophic posterior
      maxilla using 3 sinus augmentation techniques: osteotome sinus floor elevation
      (OSFE) and 1- and 2-step lateral window techniques (LWTs). MATERIALS AND METHODS:
      Data were retrospectively collected from 50 patients, 29 to 85 years old. One
      hundred twenty-eight implants were subdivided based on sinus augmentation
      technique as determined by available native bone height. Thirty-three implants
      were placed using OSFE in at least 8.0 mm of bone. Forty-four implants were
      synchronously placed using 1-step LWT in 3.0 to 7.9 mm of bone. In cases with
      less than 3.0 mm of bone, the 2-step LWT was performed and the remaining 51
      implants were placed after a period of healing. Implant stability quotient (ISQ)
      was recorded from RFA at stage 1 and subsequently at stage 2 (follow-up) 3 to 12
      months later. Statistical analysis was completed using t test and analysis of
      variance to assess differences in implant stability over time and among
      techniques, respectively. RESULTS: ISQ values at placement averaged 70.9, 68.9,
      and 72.2 for OSFE, LWT, and LWT with delayed placement, respectively. These
      differences were not statistically significant (P = .2). At stage 2 (follow-up),
      average ISQ values were 76.7, 77.7, and 78.7 for OSFE, LWT, and LWT with delayed
      placement, respectively. These differences were not statistically significant (P
      = .3). In contrast, differences in ISQ at stage 2 (follow-up) versus stage 1 were
      statistically significant for all 3 techniques (P < .01). OSFE, 1-step LWT, and 2
      step LWT yielded average increases in ISQ of 5.8, 8.8, and 6.5, respectively.
      CONCLUSIONS: The results support the use of OSFE, 1-step LWT, and 2-step LWT to
      augment bone in the atrophic edentulous posterior maxilla. All 3 methods provide
      predictable osseointegration and yield statistical increases in ISQ at stage 2
      (follow-up) compared with time of placement. With appropriate case selection
      according to native vertical bone height, there are no statistical differences in
      ISQ among these 3 techniques at either stage.

PMID- 25989529
TI  - Involvement of a P2X7 Receptor in the Acrosome Reaction Induced by ATP in Rat
      Spermatozoa.
AB  - The acrosome reaction (AR) is the exocytosis of the acrosomal vesicle in response
      to different physiological and non-physiological stimuli. Particularly in
      mammals, the AR is needed for sperm to fuse with the oocyte plasma membrane, and
      it occurs only in capacitated sperm. Previous evidence in the literature
      indicates that extracellular ATP induces the AR in capacitated human and bovine
      spermatozoa, but its receptor has not yet been identified. The aim of this work
      was to define a putative ATP receptor in rat spermatozoa using pharmacological
      and biochemical approaches. We found that ATP induced the AR only in capacitated
      rat spermatozoa, which was inhibited in the presence of two general inhibitors of
      ATP receptors (P2 receptors), Suramin, and oxidized ATP (oATP), and one inhibitor
      of P2X receptor (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid [PPADS]).
      In addition, the AR induced by ATP in capacitated rat spermatozoa was inhibited
      by brilliant blue-G (BB-G) and 17-beta-oestradiol, two blockers of P2X7
      receptors. Moreover, the ATP analog 2'(3')-O-(4-benzoylbenzoyl) ATP (BzATP) was
      almost 500 times more potent than ATP to induce the AR, which agrees with the
      pharmacology of a P2X7 receptor. Here, we show the presence of P2X7 receptor by
      Western blot and its localization in the tail and acrosome by indirect
      immunofluorescence. Finally, we quantify the presence of ATP in the rat oviduct
      during the estrous cycle. We found that the ATP concentration within the lumen of
      the oviduct is similar to those required to induce acrosome reaction, which agree
      with its role during in vivo fertilization. Therefore, our results strongly
      suggest that ATP induces the AR in capacitated rat spermatozoa through a P2X7
      receptor, which may be functional during in vivo fertilization.

PMID- 25989531
TI  - Deciphering Kinetic Information from Single-Molecule FRET Data That Show Slow
      Transitions.
AB  - Single-molecule FRET is one of the most powerful and widely used biophysical
      techniques in biological sciences. It, however, often suffers from limitations
      such as weak signal and limited measurement time intrinsic to single-molecule
      fluorescence measurements. Despite several ameliorative measures taken to
      increase measurement time, it is nearly impossible to acquire meaningful kinetic
      information on a molecule if conformational transitions of the molecule are
      ultraslow such that transition times (?tau?orig) are comparable to or longer than
      measurement times (deltat) limited by the finite lifetime of fluorescent dye.
      Here, to extract a reliable and accurate mean transition time from a series of
      short time traces with ultraslow kinetics, we suggest a scheme called sHaRPer
      (serialized Handshaking Repeated Permutation with end removal) that concatenates
      multiple time traces. Because data acquisition frequency f and measurement time
      (deltat) affect the estimation of mean transition time (?tau?), we provide
      mathematical criteria that f, deltat, and ?tau? should satisfy to make ?tau?
      close enough to ?tau?orig. Although application of the sHaRPer method has a
      potential risk of distorting the time constants of individual kinetic phases if
      the data are described with kinetic partitioning, we also provide criteria to
      avoid such distortion. Our sHaRPer method is a useful way to handle single
      molecule data with slow transition kinetics. This study provides a practical
      guide to use sHaRPer. 

PMID- 25989530
TI  - Association of urinary and anal incontinence with measures of pelvic floor muscle
      contractility.
AB  - OBJECTIVE: To assess the association between clinical and sonographic measures of
      pelvic floor muscle (PFM) function and symptoms of urinary and anal incontinence
      (AI). METHODS: This was a retrospective study of women seen at a tertiary
      urogynecological unit. All women had undergone a standardized interview, clinical
      examination including Modified Oxford Scale (MOS) grading, urodynamic testing and
      four-dimensional translabial ultrasound (TLUS). Cranioventral shift of the
      bladder neck (BN) and reduction in the hiatal anteroposterior (AP) diameter were
      measured using ultrasound volumes acquired on maximal PFM contraction, blinded
      against all clinical data. RESULTS: Data from 726 women with a mean age of 56 +/-
      13.7 (range, 18-88) years and a mean body mass index of 29 +/- 6.1 (range, 17-55)
      kg/m(2) were analyzed. Stress (SI) and urge (UI) urinary incontinence were
      reported by 73% and 72%, respectively, and 13% had AI. Mean MOS grade was 2.4 +/-
      1.1 (range, 0-5). Mean cranioventral BN shift on TLUS was 7.1 +/- 4.4 (range, 0.3
      25.3) mm; mean reduction in AP hiatal diameter was 8.6 +/- 4.8 (range, 0.3-31.3)
      mm. On univariate analysis, neither MOS nor TLUS measures were strongly
      associated with symptoms of urinary incontinence or AI; associations were non
      significant except for BN displacement/SI (7.3 mm vs 6.5 mm; P = 0.028), BN
      displacement/UI (6.85 vs 7.75; P = 0.019), hiatal AP diameter/AI (9.6 mm vs 8.5
      mm; P = 0.047) and MOS/SI (2.42 vs 2.19; P = 0.013). CONCLUSIONS: In this large
      retrospective study we did not find any strong associations between sonographic
      or palpatory measures of PFM function and symptoms of urinary incontinence or AI.
      Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 25989532
TI  - Sn-Seeded GaAs Nanowires as Self-Assembled Radial p-n Junctions.
AB  - The widespread use of Au as a seed particle in the fabrication of semiconductor
      nanowires presents a fundamental limitation to the potential incorporation of
      such nanostructures into electronic devices. Although several other growth
      techniques have been demonstrated, the use of alternative seed particle metals
      remains an underexplored but potentially very promising way to influence the
      properties of the resulting nanowires while simultaneously avoiding gold. In this
      Letter, we demonstrate the use of Sn as a seed particle metal for GaAs nanowires
      grown by metal-organic vapor phase epitaxy. We show that vertically aligned and
      stacking defect-free GaAs nanowires can be grown with very high yield. The
      resulting nanowires exhibit Esaki diode behavior, attributed to very high n
      doping of the nanowire core with Sn, and simultaneous C-doping of the radial
      overgrowth. These results demonstrate that the use of alternative seed particle
      metals is a potentially important area to explore for developing nanowire
      materials with controlled material properties. 

PMID- 25989534
TI  - Pretreatment with low dose etomidate prevents etomidate-induced rat adrenal
      insufficiency by regulating oxidative stress-related MAPKs and apoptosis.
AB  - Etomidate is frequently used as an anesthetic and sedation agent in the clinic
      setting. This study determined that a low-dose pre-infusion followed by a
      continuous dose infusion of etomidate could reduce etomidate-induced adrenal
      gland insufficiency. Sixty adult male Wistar rats were used, with six rats per
      group. Based on preliminary experiments, 0.6mg/kg etomidate was selected as the
      low dose for this study. Oxidative stress and apoptosis-related proteins in the
      adrenal glands were assayed using Western blot, and serum levels of CORT and
      11beta-hydroxylase were detected using ELISA. Pretreatment with a single bolus of
      low dose etomidate significantly increased the levels of CORT and 11beta
      hydroxylase as well as the activities of superoxide dismutase (SOD), catalase
      (CAT) and glutathioneperoxidase (GPx) in the adrenal glands, but reduced nitric
      oxide (NO) production when compared to the positive group. Furthermore, Western
      blot data showed that pretreatment with low dose etomidate increased
      extracellular signal-regulated kinase1/2 (ERK1/2), CREB and bcl-2 activation, but
      suppressed the p-p38, c-JunN-terminal kinase (JNK), inducible NO synthase (iNOS),
      cleaved-caspase3, cleaved-poly-ADP-ribose polymerase (PARP), bax, and AKT
      activation. The ERK inhibitor PD98059 and the p38MAPK inhibitor SB203580
      abolished the protective effect of low dose etomidate pretreatment. These data
      demonstrated that pretreatment with low dose etomidate attenuated etomidate
      induced adrenal insufficiency to rat adrenal glands. Oxidative stress-related
      MAPKs and apoptosis proteins might be responsible for mediating the etomidate
      preconditioning effect in rats. 

PMID- 25989533
TI  - An aptasensor for selective, sensitive and fast detection of lead(II) based on
      polyethyleneimine and gold nanoparticles.
AB  - Lead (Pb), as a major environmental contaminant, could be harmful to humans when
      inhaled or ingested. In this study, we developed a sensitive, selective and fast
      colorimetric aptasensor for Pb(+2) based on polyethylenimine (PEI) and gold
      nanoparticles (AuNPs). In the absence of Pb(+2), aptamer binds to PEI. So the
      well-dispersed AuNPs remain stable with a wine-red color. Upon the addition of
      Pb(+2), a conformational change happens and a G-quadruplex aptamer/Pb(+2) complex
      is formed, leading to the aggregation of AuNPs and a color change to blue. This
      sensor showed a high selectivity toward Pb(+2) with a limit of detection (LOD) as
      low as 702pM. Moreover, our fabricated sensor was successfully applied for Pb(+2)
      detection in rat serum and tap water. 

PMID- 25989535
TI  - Sources of occupational stress in NSW and ACT dentists.
AB  - BACKGROUND: This study aimed to identify and understand the chronic sources of
      work stress in the NSW and ACT dentistry context. Further, the study examines
      whether Australian dentists are exposed to similar sources of work stress as
      dentists internationally. METHODS: A purposive sample of registered members of
      the NSW Branch of the Australian Dental Association (ADA) were interviewed.
      Participants were selected because they represented the key characteristics of
      the broader ADA population. Interviews were recorded and fully transcribed.
      Themes were identified, developed, refined and clarified using established and
      rigorous methods of interview investigation and analysis. RESULTS: A total of 18
      dentists participated in the study. Inductive content analysis was used to
      develop six main categories of chronic sources of stress. These groupings were
      time and scheduling pressures, professional concerns, patient/public perceptions
      of dentists, staffing problems, pressures associated with treating patients and
      business process stressors. CONCLUSIONS: Like their international counterparts,
      Australian dentists are subject to a variety of job-specific stressors. However,
      the most notable difference between Australian and international dentists relates
      to the business side of dentistry. It would appear that the Australian statutory,
      regulatory and industrial relations environment place unique and profound
      pressures on Australian dentists.

PMID- 25989536
TI  - Intramolecular Charge-Transfer Excited-State Processes in 4-(N,N
      Dimethylamino)benzonitrile: The Role of Twisting and the pisigma* State.
AB  - The structural processes leading to dual fluorescence of 4
      (dimethylamino)benzonitrile in the gas phase and in acetonitrile solvent were
      investigated using a combination of multireference configuration interaction
      (MRCI) and the second-order algebraic diagrammatic construction (ADC(2)) methods.
      Solvent effects were included on the basis of the conductor-like screening model.
      The MRCI method was used for computing the nonadiabatic interaction between the
      two lowest excited pipi* states (S2(La, CT) and S1(Lb, LE)) and the corresponding
      minimum on the crossing seam (MXS) whereas the ADC(2) calculations were dedicated
      to assessing the role of the pisigma* state. The MXS structure was found to have
      a twisting angle of ~50 degrees . The branching space does not contain the
      twisting motion of the dimethylamino group and thus is not directly involved in
      the deactivation process from S2 to S1. Polar solvent effects are not found to
      have a significant influence on this situation. Applying Cs symmetry
      restrictions, the ADC(2) calculations show that CCN bending leads to a strong
      stabilization and to significant charge transfer (CT). Nevertheless, this
      structure is not a minimum but converts to the local excitation (LE) structure on
      releasing the symmetry constraint. These findings suggest that the main role in
      the dynamics is played by the nonadiabatic interaction of the LE and CT states
      and that the main source for the dual fluorescence is the twisted internal charge
      transfer state in addition to the LE state. 

PMID- 25989539
TI  - Genetic predisposition to liver cirrhosis.

PMID- 25989537
TI  - Leptin and Neutrophil-Activating Peptide 2 Promote Mesenchymal Stem Cell
      Senescence Through Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway in
      Patients With Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) derived from patients with systemic
      lupus erythematosus (SLE) exhibit enhanced senescence. Cellular senescence has
      been reported to be induced by several inflammatory cytokines, including
      interferon-alpha (IFNalpha) and IFNgamma, that are involved in the pathogenesis
      of SLE. We undertook this study to investigate whether the inflammatory
      environment in SLE could affect MSC senescence. METHODS: Cellular senescence was
      measured by staining of senescence-associated beta-galactosidase and by
      expression of the cell cycle inhibitors p53 and p21. Eighty cytokines and
      chemokines in serum from healthy controls and patients with SLE were identified
      by cytokine antibody array. RESULTS: SLE serum promoted senescence of MSCs, which
      was reversed by the phosphatidylinositol 3-kinase (PI3K)/Akt signaling inhibitor
      LY294002 but not by the JAK/STAT inhibitor AG490 and not by the MEK/ERK inhibitor
      PD98059. Cytokine antibody array analysis revealed that leptin and neutrophil
      activating peptide 2 (NAP-2) were the 2 factors most significantly elevated in
      SLE serum compared with normal serum. Blockade of leptin or NAP-2 in MSC cultures
      abolished SLE serum-induced senescence, while direct addition of these 2 factors
      could promote senescence in cultures of normal MSCs. Inhibition of PI3K/Akt
      signaling with LY294002 reduced leptin- and NAP-2-induced senescence in MSCs.
      CONCLUSION: Taken together, our data show that leptin and NAP-2 act
      synergistically to promote MSC senescence through enhancement of the PI3K/Akt
      signaling pathway in SLE patients.

PMID- 25989540
TI  - Oxytocin encourages maternal learning.

PMID- 25989542
TI  - Transgenerational effects of BPA.

PMID- 25989543
TI  - Refining HDAC inhibition to restore memory.

PMID- 25989545
TI  - Experimental biology 2015.

PMID- 25989546
TI  - Susceptibility of Sigmodon hispidus.

PMID- 25989547
TI  - Revisions to the animal welfare inspection guide.

PMID- 25989548
TI  - Hypothermia as anesthesia for 10-d-old rats.

PMID- 25989549
TI  - Response to Protocol Review Scenario: Many potential options.

PMID- 25989550
TI  - Response to Protocol Review Scenario: Protocol is acceptable.

PMID- 25989551
TI  - Response to Protocol Review Scenario: Justify, justify, justify.

PMID- 25989552
TI  - Blood collection in the guinea pig (Cavia porcellus).
AB  - Guinea pigs are useful animal models for the study of many human diseases
      including diabetes mellitus and infectious diseases. Often, these studies involve
      collecting blood samples of considerable volume. This column describes safe
      techniques for restraint and blood collection from the jugular vein and cranial
      vena cava from alert and anesthetized guinea pigs. 

PMID- 25989554
TI  - Quality testing of autoclaved rodent drinking water during short-term and long
      term storage.
AB  - All animals need clean water to drink. At the authors' animal facility, drinking
      water for immunocompromised rodents is filtered by reverse osmosis, acidified
      during bottling and sterilized in an autoclave. Autoclaved water bottles can be
      stored in unopened autoclave bags for 7 d or in opened bags for 2 d; if not used
      during that time, they are emptied, cleaned, refilled and sterilized again. The
      authors wished to determine whether the storage period of 2-7 d was adequate and
      necessary to ensure the quality of drinking water. They tested water bottles for
      pH levels and for the presence of adenosine triphosphate as a measure of organic
      contamination during short-term and long-term storage. The pH of autoclaved
      drinking water generally remained stable during storage. Furthermore, no
      instances of organic contamination were detected in autoclaved water bottles
      stored for up to 22 d in unopened bags and only one instance was detected in
      bottles stored for up to 119 d in opened bags in a room with individually
      ventilated cages. On the basis of these findings, the acceptable storage period
      for autoclaved water bottles in opened bags at the authors' facility was extended
      to 21 d. 

PMID- 25989555
TI  - The need for econometric research in laboratory animal operations.
AB  - The scarcity of research funding can affect animal facilities in various ways.
      These effects can be evaluated by examining the allocation of financial resources
      in animal facilities, which can be facilitated by the use of mathematical and
      statistical methods to analyze economic problems, a discipline known as
      econometrics. The authors applied econometrics to study whether increasing per
      diem charges had a negative effect on the number of days of animal care purchased
      by animal users. They surveyed animal numbers and per diem charges at 20 research
      institutions and found that demand for large animals decreased as per diem
      charges increased. The authors discuss some of the challenges involved in their
      study and encourage research institutions to carry out more robust econometric
      studies of this and other economic questions facing laboratory animal research. 

PMID- 25989557
TI  - 'Do no harm' in training.

PMID- 25989558
TI  - Ain't no shame in namin'.

PMID- 25989556
TI  - The potential for nutritional components of food items used for enrichment of
      research animals to act as confounding variables in toxicology studies.
AB  - Produce and other non-certified foods may be provided to laboratory animals for
      enrichment, but this practice can generate scientific concerns, particularly if
      these food items contain nutrients that are pharmacologically active or affect
      animals' consumption of the basal diet. The author reviews information on
      potential for a number of nutritional components of food items to affect study
      data. On the basis of published effect levels, he proposes an upper limit for the
      consumption of each component in enrichment items relative to the amount present
      in a standard basal diet. He then assesses the amounts of these nutritional
      components in a broad range of food enrichment items and proposes a maximum
      serving size for each item for several common laboratory animals. Total caloric
      content and sugar content are the limiting components for many enrichment food
      items, but most items may be used as enrichment for laboratory animals without
      affecting study results, as long as the amounts of the items provided are
      managed. 

PMID- 25989559
TI  - Network of compliance professionals.

PMID- 25989562
TI  - Reply to Commentary by Trentham et al. on "Caged Phosphate and the Slips and
      Misses in Determination of Quantum Yields for Ultraviolet-A-Induced
      Photouncaging" by Gasser et al.

PMID- 25989563
TI  - Advanced analytical method of nereistoxin using mixed-mode cationic exchange
      solid-phase extraction and GC/MS.
AB  - Nereistoxin(NTX) was originated from a marine annelid worm Lumbriconereis
      heteropoda and its analogue pesticides including cartap, bensultap, thiocyclam
      and thiobensultap have been commonly used in agriculture, because of their low
      toxicity and high insecticidal activity. However, NTX has been reported about its
      inhibitory neuro toxicity in human and animal body, by blocking nicotinic
      acetylcholine receptor and it cause significant neuromuscular toxicity, resulting
      in respiratory failure. We developed a new method to determine NTX in biological
      fluid. The method involves mixed-mode cationic exchange based solid phase
      extraction and gas chromatography/mass spectrometry for final identification and
      quantitative analysis. The limit of detection and recovery were substantially
      better than those of other methods using liquid-liquid extraction or headspace
      solid phase microextraction. The good recoveries (97+/-14%) in blood samples were
      obtained and calibration curves over the range 0.05-20 mg/L have R2 values
      greater than 0.99. The developed method was applied to a fatal case of cartap
      intoxication of 74 years old woman who ingested cartap hydrochloride for suicide.
      Cartap and NTX were detected from postmortem specimens and the cause of the death
      was ruled to be nereistoxin intoxication. The concentrations of NTX were 2.58
      mg/L, 3.36 mg/L and 1479.7 mg/L in heart, femoral blood and stomach liquid
      content, respectively. The heart blood/femoral blood ratio of NTX was 0.76.

PMID- 25989564
TI  - Decline in activities of daily living after a visit to a Canadian emergency
      department for minor injuries in independent older adults: are frail older adults
      with cognitive impairment at greater risk?
AB  - OBJECTIVES: To compare functional decline in activities of daily living (ADLs) of
      older adults visiting emergency departments (EDs) for minor injuries according to
      frailty and cognitive status. DESIGN: Prospective cohort study. SETTING: Seven
      Canadian EDs. PARTICIPANTS: Individuals aged 65 and older who were independent in
      ADLs at baseline were recruited between March 2011 and March 2013 (N=1,114).
      MEASUREMENTS: The Older American Resources and Services (OARS) questionnaire was
      completed during the ED visit or within 7 days and 3 and 6 months after a minor
      injury to ascertain functional decline (>=1-point drop in ADL score).
      Participants were considered frail based on the Canadian Study of Health and
      Aging Clinical Frailty Scale (>=Level 4, vulnerable). Cognitive impairment was
      defined as performing below cutoffs on the Montreal Cognitive Assessment (<23/30)
      or Telephone Interview for Cognitive Status (<=31/50). Four subgroups were
      created: frail with cognitive impairment, frail without cognitive impairment,
      nonfrail with cognitive impairment, nonfrail without cognitive impairment.
      Sociodemographic and health data were also collected. RESULTS: Information on
      OARS, frailty, and cognitive impairment were available for 850 at 3 months and
      728 at 6 months; 19.9% of participants showed declining function at 3 months and
      25.3% at 6 months. After adjusting for age, number of comorbidities, and
      instrumental activity of daily living disability at baseline, frail participants
      with cognitive impairment were at significantly greater risk of functional
      decline at 3 (adjusted risk ratio (aRR)=1.89; 95% confidence interval (CI)=1.38
      2.59) and 6 (aRR=2.09; 95% CI=1.45-3.00) months than nonfrail participants
      without cognitive impairment. CONCLUSION: Easy-to-administer frailty and
      cognitive screening tools should be included in ED assessments to identify
      independent older adults at high risk of functional decline after minor injury so
      that appropriate services may be provided to prevent deterioration in ADLs.

PMID- 25989566
TI  - Geriatric care boot cAMP: an interprofessional education program for healthcare
      professionals.
AB  - In response to the need for interprofessional geriatrics education, a half-day
      geriatric care boot camp for healthcare professionals was held that covered core
      concepts in geriatric medicine: delirium and dementia, medication management,
      palliative care, ethics, and a general overview of older adults. Aspects of the
      curriculum focused on interprofessional education, and the attendees and
      presenters were healthcare professionals from a wide variety of fields. Primary
      objectives were to determine changes in knowledge of core concepts in geriatrics
      and level of comfort in caring for older adults. Secondary objectives assessed
      whether participants found the interprofessional approach beneficial and whether
      they used or shared this information with others in their professional
      activities. Participants completed pre- and postassessment surveys. Changes in
      participant understanding of each core concept were statistically significant, as
      was the change in comfort level of participants in caring for older adults.
      Furthermore, attendees found the multidisciplinary perspective of the boot camp
      beneficial. A 3-month follow-up survey assessed whether attendees applied and
      shared information learned in their own professional activities. Half of the
      respondents who reported sharing universally shared core concepts. Delirium and
      dementia information was most frequently shared. Information was most frequently
      shared with students, nurses, and patients' families. Attendees less frequently
      shared, or did not share, with physicians, physician assistants, social workers,
      physical and occupational therapists, nutritionists, and dentists. The healthcare
      professionals who may benefit greatly from future education programs are those
      with whom the boot camp information was least frequently shared; thus, they are
      appropriate targets for advertisements for future programs. 

PMID- 25989567
TI  - An early risk index: the original frailty measure?

PMID- 25989565
TI  - Changes in insulin-like growth factor-I and its binding proteins are associated
      with diabetes mellitus in older adults.
AB  - OBJECTIVES: To determine whether changes in insulin-like growth factor (IGF)
      protein levels are greater in participants with type 2 diabetes mellitus or
      worsening glycemia than in normoglycemic individuals over a 9-year follow-up
      period. DESIGN: Retrospective analysis of a cohort study. SETTING: Participants
      were recruited from North Carolina, California, Maryland, and Pennsylvania.
      PARTICIPANTS: Cardiovascular Health Study All Stars participants, a cohort study
      of community-dwelling adults aged 65 and older (N=897). MEASUREMENTS: Plasma IGF
      I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American
      Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired
      fasting glucose (IFG), and diabetes mellitus were used to classify participants
      at baseline (1996-97) and follow-up (2005-06). RESULTS: At baseline, mean age was
      76.3+/-3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT
      plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with
      normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels
      occurred in those who had diabetes mellitus at baseline (9-year changes: -9.3%
      for IGF-I, 59.7% for IGFBP-1, -13.4% for IGFBP-3), the smallest in individuals
      who remained normoglycemic at follow-up (9-year changes: -3.7% for IGF-I, 25.6%
      for IGFBP-1, -6.4% for IGFBP-3), and intermediate in those who were normoglycemic
      but developed IFG at follow-up. CONCLUSION: Degrees of glycemic impairment are
      associated with varying degrees of change in IGF protein levels. The changes
      observed in the diabetes mellitus group have been previously shown to be
      associated with heart failure, cancer, and noncancer mortality.

PMID- 25989568
TI  - Community-based comprehensive geriatric assessment of short- and long-term
      predictors of cognitive decline in elderly adults.

PMID- 25989570
TI  - An independent association between urinary incontinence and falls in chronic
      benzodiazepine users.

PMID- 25989569
TI  - Distribution of survival times in a real-world cohort of older adults with
      chronic kidney disease: the median may not be the message.

PMID- 25989572
TI  - Nonconvulsive status epilepticus: master of disguise.

PMID- 25989571
TI  - Lumbar pain as unusual presentation of bone marrow metastatic replacement by
      colon carcinoma.

PMID- 25989573
TI  - Late-onset sarcoidosis in a 77-year-old man.

PMID- 25989574
TI  - High-calorie supplements for treatment of anorexia or cachexia in older adults.

PMID- 25989575
TI  - Response to Finucane.

PMID- 25989576
TI  - Continuous sedation and death.

PMID- 25989577
TI  - Comments on "intervention with the screening tool of older persons potentially
      inappropriate prescriptions/screening tool to alert doctors to right treatment
      criteria in elderly residents of a chronic geriatric facility: a randomized
      clinical trial".

PMID- 25989578
TI  - Response to Lavan and colleagues.

PMID- 25989579
TI  - Real-world evidence supports optimally dosed thiazide-type diuretics as preferred
      in treatment regimens of older adults with hypertension.

PMID- 25989580
TI  - Response to Einhorn and colleagues.

PMID- 25989581
TI  - Value of WELLS's Pulmonary Embolism Prediction Score in Elderly Outpatients.

PMID- 25989582
TI  - Response to Richard Schreiber: diagnosing pulmonary embolism in frail older
      adults out of the hospital.

PMID- 25989583
TI  - Bioimpedance analysis and frailty.

PMID- 25989584
TI  - Effect of the overlap syndrome of depressive symptoms and delirium on outcomes in
      elderly adults with hip fracture: a comment.

PMID- 25989585
TI  - Response to safer and kulcu.

PMID- 25989586
TI  - Response to Carnevali and colleagues.

PMID- 25989587
TI  - Response to Lertxundi and colleagues.

PMID- 25989588
TI  - Confusion regarding anticholinergic burden measurement.

PMID- 25989590
TI  - Prevalence and correlates of major depressive disorder among rural-to-urban
      migrant workers in Shenzhen, China.
AB  - BACKGROUND: In China, rural-to-urban migrant workers (MWs) are a large and
      vulnerable population that may be at high risk for depression, but previous
      studies focused on depressive symptoms of MWs and no study has investigated the
      epidemiology of major depressive disorder (MDD). The objective of this study was
      to determine the prevalence and correlates of one-month and lifetime MDD among
      MWs in Shenzhen, China, and mental health services utilization of MWs with
      lifetime MDD. METHODS: A total of 3031 MWs were recruited from 10 manufacturing
      factories and interviewed with the Chinese version of the Mini International
      Neuropsychiatric Interview. RESULTS: The one-month and lifetime prevalence rates
      of MDD were 1.39% (95% CI: 0.97%, 1.80%) and 5.08% (95% CI: 4.30%, 5.86%),
      respectively. No significant gender and age-group differences were found in these
      rates. The risk factors for lifetime MDD included lower education, worse living
      condition, poorer self-perceived physical health, migration before adulthood,
      infrequently calling family members, and having done lots of jobs. Only 3.25% of
      the respondents with lifetime MDD had sought professional help prior to the
      interview. LIMITATIONS: The MW sample was selected from manufacturing factories,
      we should be cautious in generalizing our findings to MWs of other industries.
      CONCLUSIONS: Compared with the Chinese general population, MWs may have a similar
      prevalence of MDD, but the rate of lifetime mental health services use of MWs
      with lifetime MDD is extremely low. MDD is a major public health concern for this
      population. There is an urgent need to improve mental health services for MWs.

PMID- 25989592
TI  - The role and fate of inorganic nitrogen species during UVA/TiO2 disinfection.
AB  - Inorganic nitrogen species have three states including ammonia nitrogen
      (NH4(+)/NH3), nitrite (NO2(-)) and nitrate (NO3(-)) and are often found in the
      disinfection system. However, no available literature could be found on their
      role and fate in photocatalytic disinfection systems. In this study, batch
      experiments were conducted to investigate bacteria inactivation, H2O2 generated
      and inorganic nitrogen variation to understand the role and fate of inorganic
      nitrogen species during UVA/TiO2 disinfection and evaluate effects of initial pH
      and bacteria levels on the role and fate. NH4(+)/NH3 and NO2(-) inhibited the
      photocatalytic disinfection process obviously. It could be confirmed through that
      H2O2 yield used for pathogen inactivation was dependent on NH4(+)/NH3 and NO2(-)
      levels. The NH4(+)/NH3 remaining, NH4(+) remaining and NO3(-) yields in only
      NH4(+)/NH3 photocatalytic oxidation experiments were obviously different from the
      corresponding values in the photocatalytic disinfection experiments with
      NH4(+)/NH3, which confirmed that photocatalytic disinfection had an obvious
      effect on the fate of NH4(+)/NH3. However, photocatalytic disinfection had slight
      effects on the fate of NO2(-) and NO3(-). Escherischia coli inactivation rate was
      the highest in neutral solutions (Initial pH 7) while the lowest in alkaline
      solutions (Initial pH 8.5). The decrease of NH4(+)/NH3 in alkaline solutions was
      the most significant. In turn, the photocatalysis of NO2(-) was more evident in
      acidic solutions. E. coli inactivation was reduced with the increase of initial
      E. coli concentrations. The initial bacteria concentrations significantly
      influenced the increase of NH4(+)/NH3, NH4(+) and NO3(-), but slightly impacted
      the decrease of NO2(-).

PMID- 25989591
TI  - In vitro bioassays to evaluate complex chemical mixtures in recycled water.
AB  - With burgeoning population and diminishing availability of freshwater resources,
      the world continues to expand the use of alternative water resources for
      drinking, and the quality of these sources has been a great concern for the
      public as well as public health professionals. In vitro bioassays are
      increasingly being used to enable rapid, relatively inexpensive toxicity
      screening that can be used in conjunction with analytical chemistry data to
      evaluate water quality and the effectiveness of water treatment. In this study, a
      comprehensive bioassay battery consisting of 36 bioassays covering 18 biological
      endpoints was applied to screen the bioactivity of waters of varying qualities
      with parallel treatments. Samples include wastewater effluent, ultraviolet light
      (UV) and/or ozone advanced oxidation processed (AOP) recycled water, and
      infiltrated recycled groundwater. Based on assay sensitivity and detection
      frequency in the samples, several endpoints were highlighted in the battery,
      including assays for genotoxicity, mutagenicity, estrogenic activity,
      glucocorticoid activity, arylhydrocarbon receptor activity, oxidative stress
      response, and cytotoxicity. Attenuation of bioactivity was found to be dependent
      on the treatment process and bioassay endpoint. For instance, ozone technology
      significantly removed oxidative stress activity, while UV based technologies were
      most efficient for the attenuation of glucocorticoid activity. Chlorination
      partially attenuated genotoxicity and greatly decreased herbicidal activity,
      while groundwater infiltration efficiently attenuated most of the evaluated
      bioactivity with the exception of genotoxicity. In some cases, bioactivity (e.g.,
      mutagenicity, genotoxicity, and arylhydrocarbon receptor) increased following
      water treatment, indicating that transformation products of water treatment may
      be a concern. Furthermore, several types of bioassays with the same endpoint were
      compared in this study, which could help guide the selection of optimized methods
      in future studies. Overall, this research indicates that a battery of bioassays
      can be used to support decision-making on the application of advanced water
      treatment processes for removal of bioactivity.

PMID- 25989593
TI  - Mechanisms of enhanced total organic carbon elimination from oxalic acid
      solutions by electro-peroxone process.
AB  - Electro-peroxone (E-peroxone) is a novel electrocatalytic ozonation process that
      combines ozonation and electrolysis process to enhance pollutant degradation
      during water and wastewater treatment. This enhancement has been mainly
      attributed to several mechanisms that increase O3 transformation to .OH in the E
      peroxone system, e.g., electro-generation of H2O2 from O2 at a carbon-based
      cathode and its subsequent peroxone reaction with O3 to .OH, electro-reduction of
      O3 to .OH at the cathode, and O3 decomposition to .OH at high local pH near the
      cathode. To get more insight how these mechanisms contribute respectively to the
      enhancement, this study investigated total organic carbon (TOC) elimination from
      oxalic acid (OA) solutions by the E-peroxone process. Results show that the E
      peroxone process significantly increased TOC elimination rate by 10.2-12.5 times
      compared with the linear addition of the individual rates of corresponding
      ozonation and electrolysis process. Kinetic analyses reveal that the
      electrochemically-driven peroxone reaction is the most important mechanism for
      the enhanced TOC elimination rate, while the other mechanisms contribute minor to
      the enhancement by a factor of 1.6-2.5. The results indicate that proper
      selection of electrodes that can effectively produce H2O2 at the cathode is
      critical to maximize TOC elimination in the E-peroxone process.

PMID- 25989594
TI  - Chronic Obstructive Pulmonary Disease: CT Quantification of Airway Dimensions,
      Numbers of Airways to Measure, and Effect of Bronchodilation.
AB  - PURPOSE: To determine the effect of bronchodilation on airway indexes reflecting
      airway disease in patients with chronic obstructive pulmonary disease (COPD) and
      to determine the minimum number of segmental and subsegmental airways required.
      MATERIALS AND METHODS: This study was approved by the local ethical committee,
      and written informed consent was obtained from all subjects. Twenty patients with
      COPD who had undergone pre- and postbronchodilator pulmonary function tests and
      computed tomographic (CT) examinations were prospectively included. Eight healthy
      volunteers underwent two CT examinations. Luminal area and wall thickness (WT) of
      third- and fourth-generation airways were measured twice by three readers. The
      percentage of total airway area occupied by the wall and the square root of wall
      area at an internal perimeter of 10 mm (?WAPi10) were calculated. The effects of
      pathologic status, session, reader, bronchodilation, and CT examination were
      assessed by using mixed linear model analyses. The number of airways to measure
      for a definite percentage error of ?WAPi10 was computed by using a bootstrap
      method. RESULTS: There were no significant session, reader, or bronchodilation
      effects on WT in third-generation airways and ?WAPi10 in patients with COPD (P
      values ranging from .187 to >.999). WT in third-generation airways and ?WAPi10
      were significantly different in patients with COPD and control subjects (P = .018
      and <.001, respectively). Measuring 12 third- or fourth-generation airways
      ensured a maximal 10% error of ?WAPi10. CONCLUSION: WT in third-generation
      airways and ?WAPi10 are not significantly different before and after
      bronchodilation and are different in patients with COPD and control subjects.
      Twelve is the minimum number of third- or fourth-generation airways required to
      ensure a maximal 10% error of ?WAPi10. ((c)) RSNA, 2015 Clinical trial
      registration no. NCT01142531 Online supplemental material is available for this
      article.

PMID- 25989595
TI  - Extra-gonadal steroids modulate non-breeding territorial aggression in weakly
      electric fish.
AB  - The neuroendocrine control of intraspecific aggression is a matter of current
      debate. Although aggression in a reproductive context has been associated with
      high levels of circulating androgens in a broad range of species, it has also
      been shown to occur during the non-breeding season when gonads are regressed and
      plasma steroid hormone levels are low. In mammals and birds the aromatization of
      androgens into estrogens plays a key role in the regulation of aggression in both
      the breeding and non-breeding seasons. This is the first study in a teleost fish
      to explore the role of steroids in the modulation of non-breeding aggression.
      Gymnotus omarorum is a highly aggressive teleost fish that exhibits aggression
      all year-round. We analyzed male-male non-breeding agonistic behavior, compared
      circulating 11-Ketotestosterone (11-KT) levels between dominants and isolated
      males, assessed the regulatory role of aromatization of androgens into estrogens,
      and evaluated the gonads as a source of these sex steroids. We found that high
      levels of aggression occurred in the non-breeding season despite low plasma 11-KT
      levels, and that there was no difference in 11-KT levels between dominant and
      isolated males. We demonstrated that acute aromatase inhibition decreased
      aggression, distorted contest dynamics, and affected expected outcome. We also
      found that castrated individuals displayed aggressive behavior indistinguishable
      from non-castrated males. Our results show, for the first time in teleost fish,
      that territorial aggression of G. omarorum during the non-breeding season depends
      on a non-gonadal estrogenic pathway. 

PMID- 25989598
TI  - Representation of the Numerosity 'zero' in the Parietal Cortex of the Monkey.
AB  - Zero is a fundamental concept in mathematics and modern science. Empty sets are
      considered a precursor of the concept of numerosity zero and a part of numerical
      continuum. How is numerosity zero (the absence of visual items) represented in
      the primate cortex? To address this question, we trained monkeys to perform
      numerical operations including numerosity zero. Here we show a group of neurons
      in the posterior parietal cortex of the monkey activated in response to
      numerosity 'zero'. 'Zero' neurons are classified into exclusive and continuous
      types; the exclusive type discretely encodes numerical absence and the continuous
      type encodes numerical absence as a part of a numerical continuum. "Numerosity
      zero" neurons enhance behavioral discrimination of not only zero numerosity but
      also non-zero numerosities. Representation of numerosity zero in the parietal
      cortex may be a precursor of non-verbal concept of zero in primates. 

PMID- 25989599
TI  - Ebola and mental health.

PMID- 25989597
TI  - Obesity accelerates cognitive decline by aggravating mitochondrial dysfunction,
      insulin resistance and synaptic dysfunction under estrogen-deprived conditions.
AB  - Chronic consumption of a high-fat diet (HF) causes peripheral insulin resistance,
      brain insulin resistance, brain mitochondrial dysfunction and cognitive
      impairment. Estrogen deprivation has also been found to impair cognition.
      However, the combined effect of both conditions on the brain is unclear. We
      hypothesized that estrogen deprivation causes brain insulin resistance, brain
      mitochondrial dysfunction, hippocampal synaptic dysfunction and cognitive
      impairment, and that consumption of a HF accelerates these impairments in an
      estrogen-deprived condition. Seventy-two female rats were divided into sham (S)
      and ovariectomized (O) groups. Rats in each group were further divided into two
      subgroups to be fed with either a normal diet (ND) or HF for 4, 8 and 12 weeks.
      At the end of each period, the Morris water maze test was carried out, after
      which the blood and brain were collected for metabolic and brain function
      analysis. Obesity, peripheral insulin resistance, increased brain oxidative
      stress and hippocampal synaptic dysfunction were observed at the eighth week in
      the NDO, HFS and HFO rats. However, these impairments were worse in the HFO rats.
      Interestingly, brain insulin resistance, brain mitochondrial dysfunction and
      cognitive impairment developed earlier (week eight) in the HFO rats, whereas
      these conditions were observed later at week 12 in the NDO and HFS rats. Either
      estrogen deprivation or HF appears to cause peripheral insulin resistance,
      increased brain oxidative stress, hippocampal synaptic dysfunction, brain
      mitochondrial dysfunction and brain insulin resistance, which together can lead
      to cognitive impairment. A HF accelerates and aggravates these deleterious
      effects under estrogen-deprived conditions.

PMID- 25989596
TI  - Reproductive state modulates testosterone-induced singing in adult female
      European starlings (Sturnus vulgaris).
AB  - European starlings (Sturnus vulgaris) exhibit seasonal changes in singing and in
      the volumes of the neural substrate. Increases in song nuclei volume are mediated
      at least in part by increases in day length, which is also associated with
      increases in plasma testosterone (T), reproductive activity, and singing behavior
      in males. The correlations between photoperiod (i.e. daylength), T, reproductive
      state and singing hamper our ability to disentangle causal relationships. We
      investigated how photoperiodic-induced variation in reproductive state modulates
      the effects of T on singing behavior and song nuclei volumes in adult female
      starlings. Female starlings do not naturally produce measureable levels of
      circulating T but nevertheless respond to exogenous T, which induces male-like
      singing. We manipulated photoperiod by placing birds in a photosensitive or
      photorefractory state and then treated them with T-filled or empty silastic
      implants. We recorded morning singing behavior for 3 weeks, after which we
      assessed reproductive condition and measured song nuclei volumes. We found that T
      treated photosensitive birds sang significantly more than all other groups
      including T-treated photorefractory birds. All T-treated birds had larger song
      nuclei volumes than with blank-treated birds (despite photorefractory T-treated
      birds not increasing song-rate). There was no effect of photoperiod on the song
      nuclei volumes of T-treated birds. These data show that the behavioral effects of
      exogenous T can be modulated by reproductive state in adult female songbirds.
      Furthermore, these data are consistent with other observations that increases in
      singing rate in response to T are not necessarily due to the direct effects of T
      on song nuclei volume.

PMID- 25989601
TI  - Anisotropy in the Raman scattering of a CaFeO2.5 single crystal and its link with
      oxygen ordering in Brownmillerite frameworks.
AB  - Periodic DFT calculations allow an understanding of the strong orientation
      dependent Raman spectra of oriented CaFeO2.5 single crystals. Modes involving the
      oscillation of the apical oxygen (O(ap)) atoms perturb the induced electric
      dipoles. These are formed by anisotropy in the charge distribution and are found
      to be strongly enhanced when the electric field of the linearly polarized laser
      line is parallel to the b axis. For the CaFeO2.5 ordered system, strong
      polarizability of these modes corresponds to strong Raman intensities.
      Conversely, the apical oxygen disorder observed in low-temperature oxygen
      conducting SrFeO2.5 destroys the long-range coherence of the respective Raman
      modes, which consequently show a strongly reduced intensity. This study provides
      a vibrational tool to discriminate between ordered and disordered isomorporphous
      ABO2.5 Brownmillerite frameworks. Furthermore, in combination with DFT
      calculations, we have found that the weakening of the interlayer interactions is
      responsible for the loss of ordering in Brownmillerite compounds.

PMID- 25989600
TI  - Sulfatide-Hsp70 interaction promotes Hsp70 clustering and stabilizes binding to
      unfolded protein.
AB  - The 70-kDa heat shock protein (Hsp70), one of the major stress-inducible
      molecular chaperones, is localized not only in the cytosol, but also in
      extracellular milieu in mammals. Hsp70 interacts with various cell surface
      glycolipids including sulfatide (3'-sulfogalactosphingolipid). However, the
      molecular mechanism, as well as the biological relevance, underlying the
      glycolipid-Hsp70 interaction is unknown. Here we report that sulfatide promotes
      Hsp70 oligomerization through the N-terminal ATPase domain, which stabilizes the
      binding of Hsp70 to unfolded protein in vitro. We find that the Hsp70 oligomer
      has apparent molecular masses ranging from 440 kDa to greater than 669 kDa. The C
      terminal peptide-binding domain is dispensable for the sulfatide-induced oligomer
      formation. The oligomer formation is impaired in the presence of ATP, while the
      Hsp70 oligomer, once formed, is unable to bind to ATP. These results suggest that
      sulfatide locks Hsp70 in a high-affinity state to unfolded proteins by clustering
      the peptide-binding domain and blocking the binding to ATP that induces the
      dissociation of Hsp70 from protein substrates. 

PMID- 25989602
TI  - A novel function of Huntingtin in the cilium and retinal ciliopathy in
      Huntington's disease mice.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by the toxic
      expansion of polyglutamine in the Huntingtin (HTT) protein. The pathomechanism is
      complex and not fully understood. Increasing evidence indicates that the loss of
      normal protein function also contributes to the pathogenesis, pointing out the
      importance of understanding the physiological roles of HTT. We provide evidence
      for a novel function of HTT in the cilium. HTT localizes in diverse types of
      cilia--including 9 + 0 non-motile sensory cilia of neurons and 9 + 2 motile
      multicilia of trachea and ependymal cells--which exert various functions during
      tissue development and homeostasis. In the photoreceptor cilium, HTT is present
      in all subciliary compartments from the base of the cilium and adjacent centriole
      to the tip of the axoneme. In HD mice, photoreceptor cilia are abnormally
      elongated, have hyperacetylated alpha-tubulin and show mislocalization of the
      intraflagellar transport proteins IFT57 and IFT88. As a consequence,
      intraflagellar transport function is perturbed and leads to aberrant accumulation
      of outer segment proteins in the photoreceptor cell bodies and disruption of
      outer segment integrity, all of which precede overt cell death. Strikingly,
      endogenous mouse HTT is strongly reduced in cilia and accumulates in
      photoreceptor cell bodies, suggesting that HTT loss function contributes to
      structural and functional defects of photoreceptor cilia in HD mouse. Our results
      indicate that cilia pathology participates in HD physiopathology and may
      represent a therapeutic target.

PMID- 25989603
TI  - Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan
      poly(ethylene imine) hybrid nanoparticles: A mechanistic insight.
AB  - Integrin-targeted nanoparticles are promising for the delivery of small
      interfering RNA (siRNA) to tumor cells or tumor endothelium in cancer therapy
      aiming at silencing genes essential for tumor growth. However, during the process
      of optimizing and realizing their full potential, it is pertinent to gain a basic
      mechanistic understanding of the bottlenecks existing for nanoparticle-mediated
      intracellular delivery. We designed alphavbeta3 integrin-targeted nanoparticles
      by coupling arginine-glycine-aspartate (RGD) or RGD peptidomimetic (RGDp) ligands
      to the surface of poly(ethylene glycol) (PEG) grafted chitosan-poly(ethylene
      imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by
      alphavbeta3-targeted versus non-targeted nanoparticles was quantified in the
      human non-small cell lung carcinoma cell line H1299 expressing enhanced green
      fluorescent protein (EGFP) using a stem-loop reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) approach. Data demonstrated that the
      internalization of alphavbeta3-targeted nanoparticles was highly dependent on the
      surface concentration of the ligand. Above a certain threshold concentration, the
      use of targeted nanoparticles provided a two-fold increase in the number of siRNA
      copies/cell, subsequently resulting in as much as 90% silencing of EGFP at well
      tolerated carrier concentrations. In contrast, non-targeted nanoparticles
      mediated low levels of gene silencing, despite relatively high intracellular
      siRNA concentrations, indicating that these nanoparticles might end up in late
      endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus,
      the silencing efficiency of the chitosan-based nanoparticles is strongly
      dependent on the uptake and the intracellular trafficking in H1299 EGFP cells,
      which is critical information towards a more complete understanding of the
      delivery mechanism that can facilitate the future design of efficient siRNA
      delivery systems. 

PMID- 25989604
TI  - A detailed investigation on electro-Fenton treatment of propachlor:
      Mineralization kinetic and degradation intermediates.
AB  - In this study, electrochemical removal of propachlor from water has been
      investigated by electro-Fenton process which provides continuous electrochemical
      production of hydroxyl radical which is a highly oxidizing agent. This radical
      can react with propachlor unselectively and can oxidize it into carbon dioxide
      and water. Effects of applied current, catalyst (Fe2(SO4)3) and supporting
      electrolyte (Na2SO4) concentrations on the degradation rate of propachlor have
      been examined and determined as 200 mA, 0.20 mM and 25 mM, respectively. The
      oxidation reaction showed a second-order reaction kinetic with an absolute rate
      constant value of (3.6+/-0.2)*10(9) M(-1) s(-1) which was determined by
      competition kinetic experiments. Total organic carbon analysis was employed to
      follow the mineralization of propachlor. The total mineralization was completed
      in a seven-hour electrolysis at 300 mA indicating that the electro-Fenton process
      is very effective in the mineralization of propachlor in water. Oxidation of
      propachlor with hydroxyl radical led to the formation of intermediate species.
      Some of these species were detected and quantified by chromatographic and
      spectroscopic methods such as HPLC, GC-MS and IC. A plausible mineralization
      pathway for the electrochemical removal of propachlor was proposed based on the
      identified by-products.

PMID- 25989605
TI  - Adsorption of emerging pollutants on functionalized multiwall carbon nanotubes.
AB  - Adsorption of three representative emerging pollutants - 1,8-dichlorooctane,
      nalidixic acid and 2-(4-methylphenoxy)ethanol- on different carbon nanotubes was
      studied in order to determine the influence of the morphological and chemical
      properties of the materials on their adsorption properties. As adsorbents,
      multiwall carbon nanotubes (MWCNTs) without functionalization and with oxygen or
      nitrogen surface groups, as well as carbon nanotubes doped with nitrogen were
      used. The adsorption was studied in aqueous phase using batch adsorption
      experiments, results being fitted to both Langmuir and Freundlich models. The
      adsorption capacity is strongly dependent on both the hydrophobicity of the
      adsorbates and the morphology of the adsorbents. Thermodynamic parameters were
      determined observing strong interactions between the aromatic rings of the
      emerging pollutant and the nitrogen modified adsorbents. 

PMID- 25989606
TI  - Low-dose add-on memantine treatment may improve cognitive performance and self
      reported health conditions in opioid-dependent patients undergoing methadone
      maintenance-therapy.
AB  - An important interaction between opioid and dopamine systems has been indicated,
      and using opioids may negatively affect cognitive functioning. Memantine, a
      medication for Alzheimer's disease, increasingly is being used for several
      disorders and maybe important for cognitive improvement. Opioid-dependent
      patients undergoing methadone-maintenance-therapy (MMT) and healthy controls
      (HCs) were recruited. Patients randomly assigned to the experimental (5 mg/day
      memantine (MMT+M) or placebo (MMT+P) group: 57 in MMT+M, 77 in MMT+P. Those
      completed the cognitive tasks at the baseline and after the 12-week treatment
      were analyzed. Thirty-seven age- and gender-matched HCs, and 42 MMT+P and 39
      MMT+M patients were compared. The dropout rates were 49.4% in the MMT+P and 26.3%
      in the MMT+M. Both patient groups' cognitive performances were significantly
      worse than that of the HCs. After the treatment, both patient groups showed
      improved cognitive performance. We also found an interaction between the patient
      groups and time which indicated that the MMT+M group's post-treatment improvement
      was better than that of the MMT+P group. Memantine, previously reported as
      neuroprotective may attenuate chronic opioid-dependence-induced cognitive
      decline. Using such low dose of memantine as adjuvant treatment for improving
      cognitive performance in opioid dependents; the dose of memantine might be a
      worthy topic in future studies.

PMID- 25989607
TI  - Differential Hematopoietic Activity in White Adipose Tissue Depending on its
      Localization.
AB  - White adipose tissue (WAT) can be found in different locations in the body, and
      these different adipose deposits exhibit specific physiopathological importance
      according to the subcutaneous or abdominal locations. We have shown previously
      the presence of functional hematopoietic stem/progenitor cells (HSPC) in
      subcutaneous adipose tissue (SCAT). These cells exhibit a specific hematopoietic
      activity that contributes to the renewal of the immune cell compartment within
      this adipose deposit. In this study, we investigated whether HSPC can be found in
      visceral adipose tissue (VAT) and whether a putative difference in in situ
      hematopoiesis may be related to anatomical location and to site-specific immune
      cell content in VAT compared to SCAT. Therein, we identified for the first time
      the presence of HSPC in VAT. Using both in vitro assays and in vivo competitive
      repopulation experiments with sorted HSPC from VAT or SCAT, we showed that the
      hematopoietic activity of HSPC was lower in VAT, compared to SCAT. In addition,
      this altered hematopoietic activity of HSPC in VAT was due to their
      microenvironment, and may be related to a specific combination of secreted
      factors and extracellular matrix molecules expressed by adipose derived stromal
      cells. Our results indicate that WAT specific hematopoietic activity may be
      generalized to all adipose deposits, although with specificity according to the
      fat pad location. Considering the abundance of WAT in the body, this emphasizes
      the potential importance of this hematopoietic activity in physiopathological
      situations.

PMID- 25989608
TI  - Removal of Ca(2+) from the Oxygen-Evolving Complex in Photosystem II Has Minimal
      Effect on the Mn4O5 Core Structure: A Polarized Mn X-ray Absorption Spectroscopy
      Study.
AB  - Ca(2+)-depleted and Ca(2+)-reconstituted spinach photosystem II was studied using
      polarized X-ray absorption spectroscopy of oriented PS II preparations to
      investigate the structural and functional role of the Ca(2+) ion in the Mn4O5Ca
      cluster of the oxygen-evolving complex (OEC). Samples were prepared by low
      pH/citrate treatment as one-dimensionally ordered membrane layers and poised in
      the Ca(2+)-depleted S1 (S1') and S2 (S2') states, the S2'YZ(*) state, at which
      point the catalytic cycle of water oxidation is inhibited, and the Ca(2+)
      reconstituted S1 state. Polarized Mn K-edge XANES and EXAFS spectra exhibit
      pronounced dichroism. Polarized EXAFS data of all states of Ca(2+)-depleted PS II
      investigated show only minor changes in distances and orientations of the Mn-Mn
      vectors compared to the Ca(2+)-containing OEC, which may be attributed to some
      loss of rigidity of the core structure. Thus, removal of the Ca(2+) ion does not
      lead to fundamental distortion or rearrangement of the tetranuclear Mn cluster,
      which indicates that the Ca(2+) ion in the OEC is not critical for structural
      maintenance of the cluster, at least in the S1 and S2 states, but fulfills a
      crucial catalytic function in the mechanism of the water oxidation reaction. On
      the basis of this structural information, reasons for the inhibitory effect of
      Ca(2+) removal are discussed, attributing to the Ca(2+) ion a fundamental role in
      organizing the surrounding (substrate) water framework and in proton-coupled
      electron transfer to YZ(*) (D1-Tyr161). 

PMID- 25989609
TI  - Medically Significant Infections Are Increased in Patients With Juvenile
      Idiopathic Arthritis Treated With Etanercept: Results From the British Society
      for Paediatric and Adolescent Rheumatology Etanercept Cohort Study.
AB  - OBJECTIVE: The association between anti-tumor necrosis factor therapy and
      increased rates of infection is widely documented in adults with rheumatoid
      arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have
      been less well documented. The aims of this analysis were to compare the rates of
      medically significant infections (MSIs) in children with JIA treated with
      etanercept (ETN) versus methotrexate (MTX) and to compare the rates between
      combination therapy with ETN plus MTX and monotherapy with ETN. METHODS: A total
      of 852 ETN-treated children and 260 MTX-treated children had been recruited to
      the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort
      Study (BSPAR-ETN). MSIs included infections that resulted in death or
      hospitalization or were deemed medically significant by the clinician. This on
      drug analysis followed the patients until the first MSI, treatment
      discontinuation, the last followup, or death. Cox proportional hazards models,
      which were adjusted using propensity deciles, were used to compare rates of MSI
      between cohorts. Sensitivity analyses were conducted specifically with regard to
      serious infections (SIs), which were defined as those requiring hospitalization
      or treatment with intravenous antibiotics/antivirals. RESULTS: The ETN-treated
      cohort was older and had a longer disease duration, but the disease activity was
      similar between the cohorts. A total of 133 first MSIs were reported (109 with
      ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the
      controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval
      1.22-3.74]). The risk of MSI was higher whether patients were receiving
      combination or monotherapy. Sensitivity analysis showed no between-group
      difference in the rate of SIs, which were much less common. CONCLUSION: ETN
      therapy is associated with an increased risk of MSI; however, this increased risk
      disappears when considering only SIs, which suggests that either there were
      differences in the severity of infections and/or there was a possible reporting
      bias.

PMID- 25989610
TI  - Formation of Copper Zinc Tin Sulfide Thin Films from Colloidal Nanocrystal
      Dispersions via Aerosol-Jet Printing and Compaction.
AB  - A three-step method to create dense polycrystalline semiconductor thin films from
      nanocrystal liquid dispersions is described. First, suitable substrates are
      coated with nanocrystals using aerosol-jet printing. Second, the porous
      nanocrystal coatings are compacted using a weighted roller or a hydraulic press
      to increase the coating density. Finally, the resulting coating is annealed for
      grain growth. The approach is demonstrated for making polycrystalline films of
      copper zinc tin sulfide (CZTS), a new solar absorber composed of earth-abundant
      elements. The range of coating morphologies accessible through aerosol-jet
      printing is examined and their formation mechanisms are revealed. Crack-free
      albeit porous films are obtained if most of the solvent in the aerosolized
      dispersion droplets containing the nanocrystals evaporates before they impinge on
      the substrate. In this case, nanocrystals agglomerate in flight and arrive at the
      substrate as solid spherical agglomerates. These porous coatings are mechanically
      compacted, and the density of the coating increases with compaction pressure.
      Dense coatings annealed in sulfur produce large-grain (>1 MUm) polycrystalline
      CZTS films with microstructure suitable for thin-film solar cells.

PMID- 25989611
TI  - A systematic review and meta-analysis of ultrasound versus electrical stimulation
      for peripheral nerve location and blockade.
AB  - We systematically reviewed peripheral nerve blockade guided by ultrasound versus
      electrical stimulation. We included 26 comparisons in 23 randomised controlled
      trials of 2125 participants. Ultrasound reduced the rate of pain during the
      procedure, relative risk (95% CI) 0.60 (0.41-0.89), p = 0.01. Ultrasound with or
      without electrical stimulation reduced the rate of analgesic or anaesthetic
      rescue versus electrical stimulation alone, relative risk (95% CI) 0.40 (0.29
      0.54) and 0.29 (0.16-0.52), respectively, p < 0.0001 for both. The rate of rescue
      was unaffected by the addition of electrical stimulation to ultrasound, relative
      risk (95% CI) 1.07 (0.54-2.10), p = 0.85. Ultrasound, with or without electrical
      stimulation, reduced the pooled rate of vascular puncture, relative risk (95% CI)
      0.23 (0.15-0.37), p < 0.0001. There was no difference in the rate of
      postoperative neurological side-effects, relative risk (95% CI) 0.76 (0.53-1.09),
      p = 0.13. 

PMID- 25989612
TI  - Elemental and spectroscopic characterization of plasters from Fatih Mosque
      Istanbul (Turkey) by combined micro-Raman, FTIR and EDXRF techniques.
AB  - The characterization of the plasters and coloring agents of the wall paintings of
      Fatih Mosque have been performed using combined micro-Raman, FTIR and EDXRF
      techniques. The investigations show that the plaster used on the walls has mixed
      gypsum-lime binders. Cinnabar {HgS}, lead red {Pb3O4} and hematite {alpha-Fe2O3}
      were identified in the red surfaces. Blue color is attributed to ultramarine blue
      {Na8-10Al6Si6O24S2-4}. Green color is assigned to mixtures of green earth, copper
      phthalocyanine {Cu(C32Cl16N8)} and brochantite {CuSO4.3Cu(OH)2}. Strontium yellow
      {SrCrO4} and zinc white {ZnO} were also used to ensure the color tone. The
      results provide a basis for future restoration of wall paints. 

PMID- 25989613
TI  - Spectroscopic study of water adsorption on Li(+), TMA(+) and HDTMA(+) exchanged
      montmorillonite.
AB  - The potential of IR and NMR spectroscopy in characterization the interaction of
      water with natural and organically modified montmorillonites was introduced.
      Organoclays were prepared from Li-saturated montmorillonite (Li-S) and
      tetramethylammonium (TMA) or hexadecyltrimethylammonium (HDTMA) salts. The
      influence of organic cation size on the water vapour uptake was examined and a
      comparative study with natural clay mineral was provided. The near-IR spectra
      confirmed the reduced water content in TMA-S and HDTMA-S. After exposure of the
      samples to water vapour under various relative humidities (RH) the H2O content
      was determined. According to the adsorption isotherms the amount of water
      decreased in order Li-S>TMA-S>HDTMA-S. The intensities of the 2nuOH and [Formula:
      see text] bands, corresponding to the vibrations of H2O, gradually increased in
      hydrated samples. The (13)C MAS NMR and near-IR of hydrated organoclays confirmed
      the presence of H2O close to the cation's headgroup. NMR signals of inner -CH2-
      groups in HDTMA-S were also affected by hydration: the intensity of disordered
      gauche conformers (31.1 ppm) overtook the intensity of ordered all-trans
      conformers (33.0 ppm).

PMID- 25989614
TI  - Crystallographic, vibrational and DFT studies of 1-(2-hydroxy-4,5
      dimethylphenyl)ethanone.
AB  - Molecular structure and properties of 1-(2-hydroxy-4,5-dimethylphenyl)ethanone
      were experimentally investigated by X-ray diffraction technique and vibrational
      spectroscopy. Experimental results on the molecular structure of the reported
      compound were supported with computational studies using the density functional
      theory (DFT), with the Becke-3-Lee-Yang-Parr (B3LYP) functional and the 6
      311+G(3df,p) basis set. Potential energy distribution (PED) and potential energy
      surface (PES) analyses were performed to identify characteristic frequencies and
      reliable conformational analysis correspondingly. The compound crystallizes in
      monoclinic space group C2/c with the CO up-OH down conformation. There is a good
      agreement between the experimentally determined geometrical parameters and
      vibrational frequencies of the compound to those predicted theoretically. 

PMID- 25989616
TI  - Influence of CuO content on the structure of lithium fluoroborate glasses:
      Spectral and gamma irradiation studies.
AB  - Glasses of lithium fluoroborate of the composition LiF 15%-B2O3 85% with
      increasing CuO as added dopant were prepared and characterized by combined
      optical and FTIR spectroscopy before and after gamma irradiation. The optical
      spectrum of the undoped glass reveals strong UV absorption with two distinct
      peaks at about 235 and 310 nm and with no visible bands. This strong UV
      absorption is related to the presence of unavoidable trace iron impurity (Fe(3+))
      within the materials used for the preparation of this glass. After irradiation,
      the spectrum of the undoped glass shows a decrease of the intensity of the UV
      bands together with the resolution of an induced visible broad band centered at
      about 520 nm. The CuO doped glasses reveal the same UV absorption beside a very
      broad visible band centered at 780 nm and this band shows extension and splitting
      to several component peaks with higher CuO contents. Upon gamma irradiation, the
      spectra of all CuO-doped glasses reveal pronounced decrease of their intensities.
      The response of irradiation on the studied glasses is correlated with suggested
      photochemical reactions together with some shielding effect of the copper ions.
      The observed visible band is related to the presence of copper as distorted
      octahedral Cu(2+) ions. Infrared absorption spectra of the prepared glasses show
      repetitive characteristic triangular and tetrahedral borate units similar to that
      published from alkali or alkaline earth oxides B2O3 glasses. A suggested
      formation of (BO3/2F) tetrahedral units is advanced through action of LiF on B2O3
      and these suggested units showing the same position and number as BO4 tetrahedra.

PMID- 25989615
TI  - Synthesis, spectroscopic, coordination and biological activities of some
      transition metal complexes containing ONO tridentate Schiff base ligand.
AB  - The main target of this paper is to get an interesting data for the preparation
      and characterizations of metal oxide (MO) nanoparticles using H2L Schiff base
      complexes as precursors through the thermal decomposition procedure. Five Schiff
      base complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) metal ions were
      synthesized from 2-[(2-hydroxy-naphthalen-1-ylmethylene)-amino]-benzoic acid new
      adduct (H2L). Theses complexes were characterized using infrared, electronic,
      mass and (1)H NMR spectroscopic techniques. The elemental analysis data was
      confirmed that the stoichiometry of (metal:H2L) is 1:1 molar ratio. The molar
      conductance indicates that all of complexes are non electrolytic. The general
      chemical formulas of these complexes is [M(L)(NH3)].nH2O. All complexes are
      tetrahedral geometry. The thermal decomposition behavior of H2L hydrated and
      anhydrous complexes has been discussed using thermogravimetric analysis (TG/DTG)
      and differential thermal analyses (DTA) under nitrogen atmosphere. The
      crystalline phases of the reaction products were checked using X-ray
      diffractometer (XRD) and scanning electron microscopy (SEM). 

PMID- 25989617
TI  - Association study of forkhead box P3 gene polymorphisms with unexplained
      recurrent spontaneous abortion.
AB  - Unexplained recurrent spontaneous abortion (URSA) has been suggested to be
      associated with the failure of fetal-maternal immunological tolerance in which
      the regulatory T lymphocytes (Tregs) play a crucial role. This study evaluated
      the association between single-nucleotide polymorphisms (SNPs) in the
      forkhead/winged helix transcription factor (FOXP3) gene, a key factor for the
      development and function of Tregs, and URSA, in an Iranian population. In this
      case-control study, 195 patients with a history of URSA and101 healthy women were
      included as case and control groups respectively. Four SNPs in the FOXP3 gene,
      two in the promoter region: -924A/G and -3279C/A, and two intronic, -20G/A and
      +459T/C, were genotyped using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) analysis. The -924A/G (p<0.0001) and -20G/A
      (p=0.008) polymorphisms were found to be associated with URSA. The respective
      odds ratios (OR) for bearing -924A/G and -20G/A gene polymorphisms were 4.1 [95%
      CI 2.3-7.5] and 2.1 [95% CI 1.2-3.6] fold higher in URSA women than those in
      controls. Thus, there were significant differences in the distribution of A and G
      alleles of -924A/G and -20G/A between URSA and controls (p=0.001, OR; 3.6 [95% CI
      2.1-6.1] and p=0.006, OR; 1.6 [95% CI 1-2.6] respectively). No associations were
      found for -3279C/A and +459T/C polymorphisms between URSA and controls. These
      results suggest that polymorphisms of the FOXP3 gene might confer susceptibility
      to URSA, probably by altering FOXP3 function and/or its expression. 

PMID- 25989619
TI  - Two-in-one sample preparation for plan-view TEM.
AB  - Transmission electron microscopy (TEM) sample preparation requires special
      skills, it is time consuming and costly, hence, an increase of the efficiency is
      of primary importance. This article describes a method that duplicates the yield
      of the conventional mechanical and ion beam preparation of plan-view TEM samples.
      As a modification of the usual procedures, instead of one two different samples
      are comprised in a single specimen. The two pre-cut slabs, one from each samples,
      are embedded side by side in the window of a 3 mm dia Ti disk and the specimen is
      thinned mechanically and by ion milling until perforation that occurs at the
      interface of the two different slabs. That, with proper implementation, provides
      acceptable size thin area for the TEM study of both samples. The suitability of
      the two-in-one method has been confirmed through examples.

PMID- 25989618
TI  - Whole-Body MR Imaging in the German National Cohort: Rationale, Design, and
      Technical Background.
AB  - PURPOSE: To detail the rationale, design, and future perspective of implementing
      whole-body magnetic resonance (MR) imaging in the German National Cohort, a large
      multicentric population-based study. MATERIALS AND METHODS: All institutional
      review boards approved the study, and informed consent is obtained before study
      enrollment. Participants are enrolled from a random sample of the general
      population at five dedicated imaging sites among 18 recruitment centers. MR
      imaging facilities are equipped with identical 3.0-T imager technology and use
      uniform MR protocols. Imager-specific hardware and software settings remained
      constant over the study period. On-site and centralized measures of image quality
      enable monitoring of completeness of the acquisitions and quality of each of the
      MR sequences. Certified radiologists read all MR imaging studies for presence of
      incidental findings according to predefined algorithms. RESULTS: Over a 4-year
      period, six participants per day are examined at each center, totaling a final
      imaging cohort of approximately 30 000 participants. The MR imaging protocol is
      identical for each site and comprises a set of 12 native series to cover
      neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging
      phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis
      platform as part of a central imaging core incorporates a thin client-based
      integrative and modular data handling platform to enable multicentric off-site
      image reading for incidental findings. Scientific analysis will be pursued on a
      per-project hypothesis-driven basis. CONCLUSION: Population-based whole-body MR
      imaging as part of the German National Cohort will serve to compile a
      comprehensive image repository, will provide insight into physiologic variants
      and subclinical disease burden, and has the potential to enable identification of
      novel imaging biomarkers of risk.

PMID- 25989621
TI  - Bandgap scaling in bilayer graphene antidot lattices.
AB  - On the basis of a tight binding model we reveal how the bandgap in bilayer
      graphene antidot lattices (GALs) follows a different scaling law than in
      monolayer GALs and we provide an explanation using the Dirac model. We show that
      previous findings regarding the criteria for the appearance of a bandgap in
      monolayer GALs are equally applicable to the bilayer case. Furthermore, we
      briefly investigate the optical properties of bilayer GALs and show that
      estimates of the bandgap using optical methods could lead to overestimates due to
      weak oscillator strength of the lowest transitions. Finally, we investigate the
      effect of imposing an electric field perpendicular to the bilayer GAL structure
      and find that the bandgap tunability may be extended as compared to pristine
      bilayer graphene. 

PMID- 25989620
TI  - The Hypothermic Influence on CHOP and Ero1-alpha in an Endoplasmic Reticulum
      Stress Model of Cerebral Ischemia.
AB  - Hypoxia induced endoplasmic reticulum stress causes accumulation of unfolded
      proteins in the endoplasmic reticulum and activates the unfolded protein
      response, resulting in apoptosis through CCAAT-enhancer-binding protein
      homologous protein (CHOP) activation. In an in vitro and in vivo model of
      ischemic stroke, we investigated whether hypothermia regulates the unfolded
      protein response of CHOP and Endoplasmic reticulum oxidoreductin-alpha (Ero1
      alpha), because Ero1-alpha is suggested to be a downstream CHOP target. The gene
      expression of CHOP and Ero1-alpha was measured using Quantitative-PCR (Q-PCR) in
      rat hippocampi following global cerebral ischemia, and in hypoxic
      pheochromocytoma cells during normothermic (37  degrees C) and hypothermic (31 
      degrees C) conditions. As a result of ischemia, a significant increase in
      expression of CHOP and Ero1-alpha was observed after three, six and twelve hours
      of reperfusion following global ischemia. A stable increase in CHOP expression
      was observed throughout the time course (p < 0.01, p < 0.0001), whereas Ero1
      alpha expression peaked at three to six hours (p < 0.0001). Induced hypothermia
      in hypoxia stressed PC12 cells resulted in a decreased expression of CHOP after
      three, six and twelve hours (p < 0.0001). On the contrary, the gene expression of
      Ero1-alpha increased as a result of hypothermia and peaked at twelve hours (p <
      0.0001). Hypothermia attenuated the expression of CHOP, supporting that
      hypothermia suppress endoplasmic reticulum stress induced apoptosis in stroke. As
      hypothermia further induced up-regulation of Ero1-alpha, and since CHOP and Ero1
      alpha showed differential regulation as a consequence of both disease (hypoxia)
      and treatment (hypothermia), we conclude that they are regulated independently. 

PMID- 25989622
TI  - Functions of the two zebrafish MAVS variants are opposite in the induction of
      IFN1 by targeting IRF7.
AB  - IFNs create the first line of host cells to defense viral infection, however,
      unrestricted expression of IFN can be hazardous to the host. IRF7 is the master
      regulator of type I IFN expression. To our knowledge, non research about the
      inhibition of IFN expression by targeting IRF7 has been reported in fish. In this
      study, we reported that the splicing variant of wildtype MAVS (MAVS_tv1),
      MAVS_tv2, negatively regulated IRF7-mediated IFN production. Firstly, in vivo,
      the transcriptional levels of MAVS_tv2 in trunk kidney and spleen from the
      zebrafish infected with SVCV were monitored. Then, in vitro, the protein
      expression pattern of MAVS_tv2 in zebrafish cell lines was detected using anti
      MAVS_tv2 antibody. Furthermore, overexpression of MAVS_tv2 decreased the
      activation of IFN1 promoter that induced by IRF7 in a dose-dependent manner,
      whereas it had little effect on IRF3, a close relative of IRF7. In addition, such
      inhibition was also observed in IRF7-mediated epcIFN promoter and ISRE
      activities, but not in the activation of the promoters of type II IFNs and NF-KB,
      due to IRF7 not regulating their expression. Lastly, overexpression of MAVS_tv2
      decreased the transcriptional levels of several IFN-stimulated genes activated by
      IRF7. These findings suggest that MAVS_tv2 is a negative regulator of IFN1 by
      targeting IRF7.

PMID- 25989623
TI  - Molecular characterization of two immunity-related acute-phase proteins:
      Haptoglobin and serum amyloid A from black rockfish (Sebastes schlegeli).
AB  - Haptoglobin (Hp) and serum amyloid A (SAA) are two vital proteins involved in
      inflammatory reactions and are classified as acute-phase proteins. They are
      released from hepatocytes under inflammatory conditions to protect healthy cells
      from being damaged by pathogens or from self-destructive mechanisms. In this
      study, a previously constructed black rockfish (Sebastes schlegeli) cDNA library
      was used to identify the full-length cDNA sequences of Hp and SAA homologs (RfHp
      and RfSAA, respectively) and characterize them at the molecular level. As
      expected, in silico analysis of these homologs showed the typical domain
      architectures of their known counterparts. Open reading frames of RfHp and RfSAA
      consisted of 942-bp and 313-bp DNA sequences, respectively. The derived
      polypeptide sequence of RfHp was composed of 313 amino acids (aa) with a
      predicted molecular weight of 34 kD, whereas RfSAA had a 121-amino acid sequence
      with a molecular weight of 13 kD. Phylogenetic analysis as well as pairwise
      sequence alignment results showed that RfHp was more closely related to
      Oreochromis mossambicus from an evolutionary perspective while RfSAA was closely
      related to the Epinephelus coioides ortholog. Although both genes were expressed
      ubiquitously in the tissues analyzed, they were particularly expressed in liver
      tissue, suggesting their origin in hepatocytes. Quantitative real-time PCR
      analysis indicated that both RfHp and RfSAA were significantly up-regulated by
      both bacterial and viral stimulation in liver tissue, affirming their putative
      importance in the acute phase of first-line host immune defenses.

PMID- 25989624
TI  - Immune and stress responses in oysters with insights on adaptation.
AB  - Oysters are representative bivalve molluscs that are widely distributed in world
      oceans. As successful colonizers of estuaries and intertidal zones, oysters are
      remarkably resilient against harsh environmental conditions including wide
      fluctuations in temperature and salinity as well as prolonged air exposure.
      Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as
      filter-feeders. These unique adaptations make oysters interesting models to study
      the evolution of host-defense systems. Recent advances in genomic studies
      including sequencing of the oyster genome have provided insights into oyster's
      immune and stress responses underlying their amazing resilience. Studies show
      that the oyster genomes are highly polymorphic and complex, which may be key to
      their resilience. The oyster genome has a large gene repertoire that is enriched
      for immune and stress response genes. Thousands of genes are involved in oyster's
      immune and stress responses, through complex interactions, with many gene
      families expanded showing high sequence, structural and functional diversity. The
      high diversity of immune receptors and effectors may provide oysters with
      enhanced specificity in immune recognition and response to cope with diverse
      pathogens in the absence of adaptive immunity. Some members of expanded immune
      gene families have diverged to function at different temperatures and salinities
      or assumed new roles in abiotic stress response. Most canonical innate immunity
      pathways are conserved in oysters and supported by a large number of diverse and
      often novel genes. The great diversity in immune and stress response genes
      exhibited by expanded gene families as well as high sequence and structural
      polymorphisms may be central to oyster's adaptation to highly stressful and
      widely changing environments. 

PMID- 25989625
TI  - The effects of dietary oxidized konjac glucomannan and its acidolysis products on
      the immune response, expression of immune related genes and disease resistance of
      Schizothorax prenanti.
AB  - In the present study, KGM was degraded by H2O2 and HCl to obtain two products
      with different molecular weights: oxidized konjac glucomannan (OKGM, 4.7 * 10(5)
      Da) and low-molecular-weight oxidized konjac glucomannan (L-OKGM, 9.2 * 10(3)
      Da). The effects of the two OKGM products on IL-1beta, TNF-alpha, and TLR22 gene
      expression, and immune parameters and the resistance to Aeromonas hydrophila of
      Schizothorax prenanti were determined. The results showed that the lysozyme
      activity was significantly enhanced by the L-OKGM diets. The SOD activity was
      significantly increased by both OKGM and L-OKGM diets. The MDA level of fish fed
      the OKGM and L-OKGM diets was significantly lower than the control group. IL
      1beta mRNA level in the spleen significantly increased in all L-OKGM fed groups.
      The 8.0 g kg(-1) L-OKGM diet also significantly up-regulated IL-1beta gene
      expression in the head kidney. In the gut, IL-1beta mRNA levels were
      significantly higher in fish fed with the 8.0 g kg(-1) OKGM and 16.0 g kg(-1) L
      OKGM diets. The TNF-alpha mRNA level of L-OKGM group significantly increased in
      the spleen, head kidney and gut. High dosing of OKGM significantly up-regulated
      TNF-alpha transcription in the head kidney, while only the 8.0 g kg(-1) OKGM
      group showed significantly higher TNF-alpha mRNA expression in the mesonephros.
      Fish fed the L-OKGM diets showed significantly higher expression of TLR22 in the
      spleen, head kidney and mesonephros. After the injection of A. hydrophila, the
      8.0 g kg(-1) L-OKGM group showed a significantly higher survival rate than did
      the control group. Present study suggests that OKGM and L-OKGM can up-regulate
      immune-related gene expression and enhance disease resistance in S. prenanti, and
      L-OKGM exhibits higher immunomodulatory activity.

PMID- 25989626
TI  - The unbinding studies of vascular endothelial growth factor receptor-2 protein
      tyrosine kinase type II inhibitors.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase has two
      conformations, active and inactive conformations. Type II inhibitors bind to
      inactive conformation. It has two possible binding/unbinding paths. To explore
      the unbinding path of inhibitor 01-435 that was generated by fragment build in
      the binding pocket of VEGFR-2, molecular dynamics (MD) simulation was performed
      on the crystal structure of VEGFR-2 in complex with 01-435, then steered
      molecular dynamics (SMD) simulation was executed on the crystal structure of
      VEGFR-2 in complex with 01-435. Pull force, van der Waals and electrostatic
      interaction along the two paths were calculated by using SMD simulation. The SMD
      simulation results indicate that the more favorable path for inhibitor
      dissociation is along with the traditional ATP-channel rather than the allosteric
      pocket-channel, which is mainly due to the less electrostatic interaction that
      the ligand suffers during dissociation process along the traditional ATP-channel.

PMID- 25989628
TI  - The metabolic fate of stiripentol in the rat. Studies on cytochrome P-450
      mediated methylenedioxy ring cleavage and side chain isomerism.
AB  - Following a single oral dose (200 mg Kg (-1) of stiripentol t (1) o adult male
      Sprague-Dawley rats, a total of 15 metabolites (accounting collectively for 44%
      of the administered dose collected over 48 hr) were identified in urine by GC/MS
      techniques, while only unchanged I (accounting for a further 12.8% and 23.5% of
      the dose in two rats) was present in extracts of feces. The major pathway of
      metabolism I involved cytochrome P-450-mediated cleavage of the methylenedioxy
      ring to yield catechol derivatives. In vitro studies employing rat hepatic
      microsomal preparations showed that this reaction was associated with the
      formation of a type III optical difference spectrum, indicative of the generation
      of an inhibitory ligand-complex between a reactive metabolite of I and the
      prosthetic heme moiety of cytochrome P-450. Mechanistic studies on the origin of
      a series of metabolites of I in which the allylic alcohol side chain had been
      replaced by an isomeric 3-pentanone structure pointed to the operation of a two
      step sequence involving initial alcohol oxidation followed by olefin reduction.
      The former reaction appeared to be catalyzed in part by cytochrome P-450 enzymes.
      It is concluded that the rat represents an appropriate model for humans in the
      conduct of detailed studies of the metabolic fate of I and analogs thereof.

PMID- 25989629
TI  - [POERT2].

PMID- 25989627
TI  - On the Possibility of Facilitated Diffusion of Dendrimers Along DNA.
AB  - We investigate the electrostatics, energetics, and dynamics of dendrimer-DNA
      interactions that mimic protein-DNA complexes as a means to design facilitated
      mechanisms by which dendrimers can slide and search DNA for targets. By using all
      atom molecular dynamics simulations, we calculated the free energy profiles of
      dendrimer-binding around the DNA via umbrella sampling. We also calculated
      electrostatic interaction maps in comparison to proteins, as well as the
      dynamical changes induced by DNA-dendrimer interactions via NMR-measurable order
      parameters. Our results show that for dendrimers to go around DNA, there is a
      free-energy barrier of 8.5 kcal/mol from the DNA major groove to DNA minor
      groove, with a minimum in the major groove. This barrier height makes it unlikely
      for an all-amine dendrimer to slide along DNA longitudinally, but following a
      helical path may be possible along the major groove. Comparison of the nonbonded
      interaction energy and the interaction free-energy profiles reveal a considerable
      entropic cost as the dendrimer binds to DNA. This is also supported by the
      mobility patterns obtained from NMR-measurable order parameter values, which show
      a decreased mobility of the dendrimer N-H bond vectors in the DNA-binding mode. 

PMID- 25989630
TI  - [Surprisingly old skeleton in the cupboard].

PMID- 25989631
TI  - [HevyLiteTM - a new method for detection of monoclonal immunoglobulins].

PMID- 25989632
TI  - [Autoimmune pancreatitis - diagnostic consensus].

PMID- 25989633
TI  - [Acromegaly and pharmacotherapy].

PMID- 25989634
TI  - [Calcific uremic arteriolopathy].

PMID- 25989635
TI  - Latest lessons from other veterinary  associations.

PMID- 25989637
TI  - Rethinking our approach to bovine Johne's   disease.

PMID- 25989638
TI  - Kick-starting a national mentor program.

PMID- 25989636
TI  - Our digital space is evolving.

PMID- 25989639
TI  - Successfully integrating a flexible workforce  into your veterinary practice.

PMID- 25989640
TI  - John Kendall - WW1 veterinarian.

PMID- 25989641
TI  - What I love about Pan Pac.

PMID- 25989642
TI  - World Veterinary Association update.

PMID- 25989643
TI  - What's happening with the Veterinary Award review?

PMID- 25989644
TI  - What is a uniform?

PMID- 25989645
TI  - The elephant in the hen house.

PMID- 25989646
TI  - Deafness in Australian cattle dogs.

PMID- 25989647
TI  - Crystallographic structure and functional implications of the nitrogenase
      molybdenum-iron protein from azotobacter vinelandii.
AB  - The crystal structure of the nitrogenase molybdenum-iron protein from Azotobacter
      vinelandii has been determined at 2.7 A resolution. The alpha- and beta-subunits
      in this alpha (2) beta (2) tetramer have similar polypeptide folds. The FeMo
      cofactor is completely encompassed by the alpha-subunit, whereas the P-cluster
      pair occurs at the interface between alpha- and beta-subunits. Structural
      similarities are apparent between nitrogenase and other electron transfer
      systems, including hydrogenases and the photosynthetic reaction centre

PMID- 25989648
TI  - Spry2 regulates signalling dynamics and terminal bud branching behaviour during
      lung development--retraction.

PMID- 25989649
TI  - Neurogenetics in Argentina: diagnostic yield in a personalized research based
      clinic.
AB  - As a whole neurogenetic diseases are a common group of neurological disorders.
      However, the recognitionand molecular diagnosis of these disorders is not always
      straightforward. Besides, there is a paucity of informationregarding the
      diagnostic yield that specialized neurogenetic clinics could obtain. We performed
      a prospective,observational, analytical study of the patients seen in a
      neurogenetic clinic at a tertiary medicalcentre to assess the diagnostic yield of
      a comprehensive diagnostic evaluation that included a personalizedclinical
      assessment along with traditional and next-generation sequencing diagnostic
      tests. We included a cohortof 387 patients from May 2008 to June 2014. For sub
      group analysis we selected a sample of patientswhose main complaint was the
      presence of progressive ataxia, to whom we applied a systematic
      moleculardiagnostic algorithm. Overall, a diagnostic mutation was identified in
      27.4% of our cohort. However, if weonly considered those patients where a
      molecular test could be performed, the success rate rises to 45%. Weobtained
      diagnostic yields of 23.5 and 57.5% in the global group of ataxic patients and in
      the subset of ataxicpatients with a positive family history, respectively. Thus,
      about a third of patients evaluated in a neurogeneticclinic could be successfully
      diagnosed.

PMID- 25989650
TI  - The author responds.

PMID- 25989651
TI  - [Revaluvation of UPPP and the pharynx in patients with snoring anatomy].

PMID- 25989652
TI  - [The correlation between stanniocalcin 2 expression and prognosis in laryngeal
      squamous cell cancer].
AB  - OBJECTIVE: In this study, we have detected the expression of STC2 protein in
      laryngeal cancer and The safe incisal margin by immunohistochemical staining, to
      evaluate its correlation with clinical features and the prognosis value in
      laryngeal squamous cell cancer. METHOD: Eighty-one paraffin-embedd specimens of
      patients who underwent surgery for laryngeal cancer were collected. Clinical
      data, including date of birth, gender, tumor subsite, tumor stage, RT, and
      survival status have been recorded. The samples including laryngeal cancer
      tissues and the safe incisal margin were analyzed for the expression of STC2
      protein by immunohistochemical staining. We analyzed the correlations with STC2
      expression level and clinical data with software SPSS 18. 0. RESULT: (1)fifty-six
      cases in 81 cases (69. 1 %) are positive. In 30 cases of the safe incisal margin
      tissues, STC2 is not expressed, which shows statistically significant differences
      between the two groups (P<0. 05). (2)Overexpression of STC2 in laryngeal cancer
      were correlated with the tumor clinical stage and N stage, T stage, tumor site
      location and histological grade (P<0. 05), but not with genderor age (P> 0. 05).
      (3)The result showed that the 3-year survival rate is 74. 1%, according to the
      survival analysis by STC2, STC2 positive group has poorer outcome versus the
      negative group. (4)The clinical stage displayed the independent value in
      predicting the tumor prognosis of laryngeal cancer (P<0. 05), not the expression
      level of STC2. CONCLUSION: Overexpression of STC2 in laryngeal cancer patients is
      correlated with poor outcome, which means STC2 positive group has poorer
      prognosis than the STC2 negative group.

PMID- 25989653
TI  - [Expression of CDK4 and p16 in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of CDK4 and p16 in laryngeal squamous
      cell carcinoma (LSCC) tissues. METHOD: The expressions of CDK4 and p16 in 30
      cases of LSCC tissues and 20 cases of edge tissues were detected by
      immunohistochemical technology SP method, and discuss their correlation with
      clincial pathology and clinical stage of LSCC. RESULT: The positive rates of CDK4
      and p16 were 63. 3 %,46. 7% in LSCC tissues, and the positive rates were 25%, 90%
      in edge tissues. The expression of CDK4 in LSCC tissues was significantly higher
      than that in edge tissues(P<0. 05), which was not associated with the clincial
      pathology and clinical stage(P> 0. 05); The expression of p16 in LSCC tissues was
      significantly lower than that in edge tissues(P<0. 05), it was associated with
      the clincial pathology (P<0. 05), but not associated with clinical stage(P>0. 05)
      ;there is a negative correlation between CDK4 and p16 (r= -0. 786, P<0. 05).
      CONCLUSION: Low expression of p16 and high expression of CDK4 may play an
      important role in the development of LSCC and the low expression of p16 in LSCC
      tissue could be used as important reference markers of malignant degree of
      tumour.

PMID- 25989654
TI  - [Detection of cytokeratin18 and cytokeratin19 gene expression in blood and tumor
      tissue of nasopharyngeal carcinoma patients by RT-PCR].
AB  - Abstract OBJECTIVE: To measure the expression of CK18 and CK19 in the cells from
      peripheral blood and tumor tissue of the nasopharyngeal carcinoma patients,to
      test whether CK 18 and CK 19 could be biomarkers of nasopharyngeal carcinoma
      fordiagnosis. METHOD: The mRNA was extracted from the blood and carcinoma tissue
      of nasopharyngeal carcinoma and was reversed transcription to cDNA. The 3 pairs
      primers were designed for RT-PCR and the fold value was calculated to evaluated
      expression by DeltaCT. RESULT: There are no statistical differences between the
      CK18 and CK19 gene expression and the gender, age and metastasis in tumor tissue
      of 45 nasopharyngeal carcinoma patients (P>0. 05). There are significant
      differences among 3 pathological stages and 2 genes expressed increase as the
      grade malignancy (P<0. 05). The detecting of the 2 genes expression from blood
      cells shows that CK18 and CK19 had a high positive ratio 64% and 75%
      respectively. Meanwhile this method showed a same detection characteristic in
      tumor and blood, the positive.rate of CK18 and CK19 genes in metastasis is higher
      than non-metastasis. The results showed CK18 has a high specificity and CK19 has
      a high sensitivity for prognosis and all relapsed cases are associated with the
      expression of CK18 and CK19. CONCLUSION: CK18 and CK19 may be used as biomarkers
      of nasopharyngeal carcinoma for diagnosis.

PMID- 25989655
TI  - [Clinical analysis of 38 cases of petrous apex cholesteatoma].
AB  - OBJECTIVE: To explore the clinical characteristics, diagnosis method and
      treatment of petrous apex cholesteatoma. METHOD: A retrospective analysis was
      taken with respects to the clinical characteristics, diagnosis and surgical
      management of 38 patients who underwent surgery for petrous apex cholesteatoma in
      our department. RESULT: (1)31 patients had unilateral hearing loss and facial
      paralysis of different degree, 27 patients were firstly characterized with
      hearing loss, and followed by facial paralysis. 6 cases had facial paralysis as
      the main performance. (2)17 patients had syndrome of tinnitus, and 15 patients
      had syndrome of vertigo and 4 cases of severe pain of ear. (3)All patients had
      petrous bone destroy with high resolution CT scan, while MRI suggests the
      presence of pathological changes in petrous apex. (4)All patients were taken
      surgeries to remove the lesion, and translabyrinth approach was chosen for 23
      patients, middle cranial fossa approach is 12, while 3 case has choose endoscopic
      approach. 8 cases were operated with facial nerve decompression. 7 cases was
      taken end to end anastomosis. 3 cases of great auricular nerve transplantation.
      There is no recurrence in follow-up of 1 years to 2 years. CONCLUSION: The
      clinical manifestations of petrous apex cholesteatoma lack specificity, and high
      resolution CT and MRI has important value in the diagnosis of petrous apex
      cholesteatoma. The strategy of surgical operation should be taken according to
      the classification, location of petrous apex cholesteatoma as well as hearing
      level and facial nerve function with patients.

PMID- 25989656
TI  - [Priliminary study of pedicled sternocleidomastoid clavicular periosteocutaneous
      flap to repair the laryngotracheal defect].
AB  - OBJECTIVE: To investigate the feasibility of utilizing pedicled
      sternocleidomastoid clavicular periosteocutaneous flap to reconstruct the
      laryngotracheal defect after tumor resection. METHOD: To review 6 cases of
      laryngotracheal defect resulting from resction of thyroid papillary
      carcinoma(4/6) or subglottic laryngeal carcinoma (2/6) (T1~2N1~2M0 , UICC,2002),
      laryngotracheal stenting was also employed in all cases. Half a year after
      surgery, the stoma was sutured if no local recurrence took place and safety was
      proved after tracheal tube had been obstructed for days. The follow-up time
      lasted from half a year to 3 years. RESULT: Four cases (4/6) were extubated
      successfully without event, one case could intermittently plug the tracheal tube.
      One patient couldn't breath with tracheal tube plugging. CONCLUSION: To
      reconstruct the laryngotracheal defect with pedicled sternocleidomastoid
      clavicular.periosteocutaneous flap after tumor resection is feasible in selected
      cases and could get satisfactory clinical results either in respiration or
      phonation.

PMID- 25989657
TI  - [The value of central lymph node dissection in surgical treatment of papillary
      thyroid carcinoma].
AB  - OBJECTIVE: To discuss the role of the central lymph node dissection in the
      treatment of papillary thyroid carcinoma. METHOD: Collect 136 patients who
      underwent thyroidectomy with papillary thyroid carcinoma in our hospital in 2011
      2012,all are conducted with lymph node dissection in the central area as well as
      resection of primary lesion. Functionl lateral neck lymph node dissection were
      used for patients with clinical lateral neck lymph node metastasis. RESULT: In
      136 patients, 56. 6%(77/136) of the central lymph node metastasis were detected.
      Positive rate was 47. 5% in 101 cN0 patients and 82. 9% in 35 cN1 patients.
      CONCLUSION: In the case of not increasing risk of surgery, resection of thyroid
      cancer primary lesion the central lymph node at the same time is a surgical
      procedure to be recommended.

PMID- 25989658
TI  - [Clinical features of thyroglossal duct carcinoma].
AB  - OJECTIVE: To analyze the cinicopathological features, treatments, and prognosis
      of patients with papillary TDCa. METHOD: A retrospective study was conducted of
      the medical records of our hospital for cases of TDCa. General clinical
      information including diagnostic criteria and treatments was obtained and
      analyzed. A literature review was also conducted. RESULT: There were 160 cases of
      thyroglossal duct anomalies hospitalized in Peking Union Medical College Hospital
      in the past 20 years, and TDCa was diagnosed in 3 (1. 88%) cases. All 3 cases
      underwent local radical resections, and papillary TDCa was diagnosed based on the
      pathology examination. Selective neck dissection was chosen in one which was
      confirmed with cervical lymphatic metastasis. All patients were followed up with
      no recurrences or metastasis. CONCLUSION: The incidence of TDCa is very low and
      the pathology examination is the only way to confirm the diagnosis. Surgery,
      especially Sistrunk's procedure, is the treatment of choice, with low
      complications and recurrence. In the presence of cervical lymphadenopathy,
      selective neck dissection should be considered.

PMID- 25989659
TI  - [Reduced expression of Diceri is associated with poor prognosis in patients with
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: Dicerl plays an important role in generation of microRNA, the purpose
      of this study was to evaluate Dicerl expression and its prognostic value in
      nasopharyngeal carcinoma (NPC). METHOD: The protein expression of Dicerl was
      examined by immunohistochemistry in 276 NPC specimens, and the mRNA levels of
      Dicerl were analyzed by qRT-PCR in 56 NPC and 11 nasopharyngitis tissues. Cox
      regression analysis was used to identify independent prognostic factors, and a
      prognostic score model was constructed for survival prediction. RESULT:
      Expression of Dicerl was downregulated in NPC tissues at both the mRNA and the
      protein levels, and there was a notable positive correlation between the
      expression levels of Dicerl mRNA and protein. Low Dicerl expression was
      positively correlated with distant metastasis (P<0. 01) and death (P<0. 05). In
      addition, low expression of Dicerl was significantly associated with poorer
      overall survival (HR = 2. 32, 95% CI: 1. 30 ~ 4. 14, P<0. 01) and poorer distant
      metastasis-free survival (HR = 2. 56, 95% CI: 1. 39 ~ 4. 74, P<0. 01).
      Furthermore, multivariate analysis showed that low expression of Dicerl and tumor
      node-metastasis (TNM) stage were independent prognostic indicators for NPC
      patients. A prognostic score model combining the Dicerl expression and TNM stage
      had a better prognostic value than the TNM stage alone model or Dicer) expression
      alone model (P< 0. 05). CONCLUSION: Dicerl was downregulated in NPC tissues at
      both the mRNA and the protein levels, and low expression of Dicerl could be
      served as novel prognostic biomarker for NPC patients.

PMID- 25989660
TI  - [Expression of LMP2A, E-Cadherin and fibronectin in nasopharyngeal carcinoma and
      its clinical significance].
AB  - OBJECTIVE: To investigate the expression of EBV-encoded latent membrane protein
      2A (LMP2A) and epithelial-mesenchymal transformation(EMT) associated markers (E
      cadherin and fibronectin) in nasopharyngeal carcinoma (NPC) and its clinical
      significance. METHOD: The expression of LMP2A, E-cad-herin and fibronectin
      proteins in 32 cases of chronic nasopharyngeal inflammation, 56 cases of NPC and
      18 cases of NPC lymph node metastasis were examined byimmunohistochemical SP
      method. RESULT: (1)The positive rates of LMP2A in NPC and its lymph node
      metastasis were significantly higher than those of chronic nasopharyngeal
      inflammation (89. 3%vs 37. 5%o and 77. 8% vs 37. 5%) respectively (both P<0. 01);
      The normal expression rates of E-cadherin in NPC and its lymph node metastasis
      were significantly lower than those of chronic nasopharyngeal inflammation (33.
      9% vs 90. 6% and 5. 6% vs 90. 6%) respectively (both P<0. 01); The positive rates
      of fibronectin in NPC and its lymph node metastasis were significantly higher
      than those of chronic nasopharyngeal inflammation (83. 9% vs 28. 1% and 72. 2% vs
      28. 1%) respectively (both P<0. 01). (2) ZLMP2A expression were negatively
      correlated with normal expression of E-cadherin (r= -0. 387, P<0. 01), and were
      positively correlated with fibronectin (r= 0. 421, P<0. 01). (3)LMP2A, E-cadherin
      and fibronectin expression were significantly correlated with N stage and
      clinical stage (both P<0. 05), but the three proteins were not significantly
      correlated with M stage (both P> 0. 05). In addition, LMP2A and E-cadherin
      expression were significantly correlated with T stage (both P<0. 01). CONCLUSION:
      LMP2A and fibronectin expressions were increased in NPC, but normal expression of
      E-cadherin were decreased. LMP2A may promote lymph node metastasis and malignant
      progression of NPC by induce EMT through downregulation of E-cadherin and
      upregulation of fibronectin.

PMID- 25989661
TI  - [Analysis of related factors of tonsil postoperative pain].
AB  - OBJECTIVE: To explore the related factors of tonsil postoperative pain. METHOD:
      After founding databank a statistic analysis was performed on 90 cases with
      tonsillectomy who admitted in our hospital. Chi-square test were used to
      investigate the related factors for postoperative pain in those patients. RESULT:
      After Chi-square test, the important effect factors in the postoperative pain
      were gender, age, surgical methods, preemptive analgesia, physical analgesia and
      preoperative anxiety level. CONCLUSION: The pain after tonsillectomy is
      influenced by not only surgery itself, but also by preemptive analgesia,
      preoperative anxiety level and so on.

PMID- 25989662
TI  - [Surgical excision and botulinum toxin A injection for vocal process granuloma].
AB  - OBJECTIVE: To study the efficacy of treatment with microsurgery in combination
      with local injection of type A botulinum toxin for vocal process granuloma.
      METHOD: 28 patients with vocal process granuloma received endotracheal intubation
      under general anesthesia. The lesion was removed with micro-scissor and CO2
      laster under a self-retaining laryngoscope and microscope. The incision and
      mucous membrane surrounding the wound was closed with 8-0 absorbable suture. 4
      point injection of botulinum toxin type A 8-15 u was then performed along the
      thyroarytenoid muscle and arytenoid muscle of the same side. Postoperative
      medication was administered based on disease causes. RESULT: All patients
      experienced vocal cord dyskinesia of the injected side 2-3 days after surgery. At
      1 month after the surgery, wound healing was good in all the 28 patients, and the
      vocal cord movement was limited at the injected side. At 3 months, movement of
      the bilateral vocal cords was normal, and the vocal cord process mucosa was
      smooth. Patients were followed up for more than a year, and only one patient had
      recurrence in 2 months after surgery. The cure rate was 96. 4%. CONCLUSION:
      Combination of laryngeal microsurgery and type A botulinum toxin local injection
      can shorten the treatment course of vocal process granuloma.

PMID- 25989663
TI  - [Correlation between expression of ERCC1 and the treatment of cisplatin-based
      chemotherapy in local advanced nasopharyngeal carcinoma].
AB  - OBJECTIVE: To study the expression of excision repair cross-complementing 1
      (ERCC1) and the treatment of cisplatin-based chemotherapy in local advanced
      nasopharyngeal carcinoma (NPC). METHOD: The expression of ERCC1 protein in 107
      cases with NPC and in 48 normal nasopharyngeal tissues adjacent to the cancer was
      detected by immunohistochemical method. RESULT: High expression of ERCC1 was
      observed in 52 cases with NPC, and 18 cases normal nasopharyngeal tissues, there
      was no statistically significant differences between them. The expression of
      ERCC1 protein was significant correlated with patient total TNM stage, but not
      significantly correlated with age, gender, histological type, T stage and N
      stage. The recent treatment efficiency in Low ER-CCl expression cases was higher
      than high expression cases. There was statistically significant difference
      between them. In 97 follow-up cases, 2 cases died, 5 cases with liver and lung
      metastasis, there was no statistically significant difference between them.
      CONCLUSION: ERCC1 expression maybe regarded as indicator platinum based
      chemotherapy sensitivity prediction in nasopharyngeal carcinoma, and also helpful
      for formulating individualized treatment. The immunohistochemical detection is
      also simple and effective detection method for ERCC1 expression.

PMID- 25989664
TI  - [Ocular and cervical vestibular evoked myogenic potentials in patients with
      peripheral vestibular disorders].
AB  - OBJECTIVE: To observe the ocular vestibular evoked myogenic potential (oVEMP) and
      the cervical vestibular evoked myogenic potential (cVEMP) in patients with
      vestibular diseases. METHOD: From March, 2011 to March, 2012, 13 patients (14
      ears) with peripheral vestibular diseases were recruited. Each patient underwent
      conventional oVEMP and cVEMP examinations elicited by intensive air conducted
      sound (short tone burst, 500 Hz) in bilateral ears. RESULT: Thirteen cases (14
      ears) were included in this study. They were 3 cases (3 ears) with Ramsay Hunt
      syndrome, 3 cases (4 ears) with acoustic neuroma, 1 case (1 ear) with VII and
      VIII cranial nerve trauma after head injury, 2 cases (2 ears) with vestibular
      neuritis, 3 cases (3 ears) with Meniere's disease, and Icase (1 ear) with
      unilateral hypoplasia of the internal auditory canal. Altogether, oVEMP could be
      elicited in only 2 ears (14. 3%) and cVEMP were found abnormal in 11 ears (78.
      6%). CONCLUSION: The otolithic vestibular end organs and their input pathways
      could be examined by cVEMP and oVEMP examinations in patients with peripheral
      vestibular disorders.

PMID- 25989665
TI  - [The study on the proliferation and the apoptosis factors in vitro of Kolliker
      organ supporting cells in the cochlea of newborn rat].
AB  - OBJECTIVE: To study the apoptosis/proliferation of Kolliker organ supporting
      cells and to understand the prompting apoptosis factors in vivo in the supporting
      cells in the Kolliker organ by changing the environment of the cultured
      supporting cells in the Kliker organ in vitro, via the separation, culture and
      purification of the supporting cells in the K6lliker organ. METHOD: A
      combinatorial approach of enzymatic digestion and mechanical separation was
      employed to isolate and culture in vitro pure Kolliker organ supporting cells.
      The purity was tested by flow cytometry assay. And K6lliker organ supporting
      cells were harvested to detect the rate and cycle of apoptosis by flow cytometry
      after Annexin V/PI staining, to test the cell growth curve by MTT assay, and to
      observe the differential expressions of the Bcl-2, Caspase-3, Caspase-8 and
      Caspase-9 through the Realtime PCR and Western blot. The calcium, potassium and
      glutamate concentrations in the culture medium of these cells in vitro were
      changed to detect the survival rate of cells by MTT assay. RESULT: The purity of
      K6lliker organ supporting cells by flow cytometry assay was 96. 56%. And these
      cells showed no significant difference in apoptosis, but an evident linear
      growth. The results of Realtime PCR and Western blot showed that the expression
      of Bcl-2, Caspase-3, Caspase-8 and Caspase-9 mRNA and protein in all different
      time points kept stable. Furthermore, the elevation of extracellular Ca2+ might
      contribute to decrease the cell viability of supporting cells. And K+
      participated regulation of cell viability in a concentration-depending way.
      However, glutamate appeared to be a protective factor in high concentration.
      CONCLUSION: There is no significant apoptosis in vitro of the supporting cells in
      the Kolliker organ of rats, showing a linear growth. The Ca2+ in high
      concentration might contribute to the apoptosis factor of these cells. However,
      the K+ and glutamate appear to be protective factors in high concentration.

PMID- 25989666
TI  - [The vitro research of effects of Beclin1 on paclitaxel-sensitivity in laryngeal
      carcinoma cell Hep-2].
AB  - OBJECTIVE: Background: We detect the effects of Beclinl on paclitaxel-sensitivity
      in laryngeal carcinoma cell. METHOD: This study used Hep-2, Hep-2-pcDNA3. 1, Hep
      2-Beclinl as invitro model. The effect of paclitaxel on the proliferation and
      cell apoptosis of laryngeal cancer cell lines was evaluated by MTT assay and flow
      cytometry. The protein expression level of Akt and p-Akt was detected by Western
      blot. Result: After treated by paclitaxel, the inhibition rate was significantly
      higher in Hep-2-Beclin cells than in Hep-2-pcDNA3. 1 cells and Hep-2 cells (P<.
      05). After dealing with 10 tg/L paclitaxel, the apoptosis rate in Hep-2, Hep-2
      pcDNA3. 1, Hep-2-Beclinl were (23. 75 +/- 2 3. 77) %, (21. 25 +/- 4. 92) %, (32.
      50 +/- 5. 97) %, respectively. After dealing with 20ug/L paclitaxel, the
      apoptosis rate in Hep-2, Hep-2-pcDNA3. 1, Hep-2-Beclinl were (38. 75 +/- 4. 79)
      %, (38. 75+/-6. 55) %, (50. 00+/-7. 26) %, respectively. Paclitaxel-induced
      apoptosis was higher in Hep-2-Beclin cells than in Hep-2-pcDNA3. 1 cells and Hep
      2 cells (P<. 05). The result of western blot showed that the protein expression
      level of p-Akt in Hep-2-Beclin cells was lower than in Hep-2-pcDNA3. 1 cells and
      Hep-2 cells (P<0. 05) and the protein expression level of Akt was similar in
      three cell lines (P>0. 05). CONCLUSION: Beclinl enhances paclitaxel-sensitivity
      by inhibition of PI3K/Akt pathway.

PMID- 25989667
TI  - [Three cases of thyroid neoplasms complicated by tumour embolus in internal
      jugular vein].

PMID- 25989668
TI  - [Clinical application of the custom-made radial forearm flap for reconstruction
      of tongue defects].

PMID- 25989669
TI  - [Pathogens of suppurative perichondritis of ear auricle and their clinical
      significances].

PMID- 25989670
TI  - [Simple antihypertensive treatment of intermittent arterial epistaxis: a clinical
      analysis of 25 cases].

PMID- 25989671
TI  - [The hyperbaric orygen in treatment of sudden deafness effect].

PMID- 25989672
TI  - [Observation of wound healing after trans-oral laser surgery for early glottic
      carcinoma].

PMID- 25989673
TI  - [Two cases of acute pulmonary embolism in head and neck tumor surgery].
AB  - A male patient with hypopharyngeal cancer accepted operation under general
      anesthesia. Sixth day after surgery in patient with sudden chest pain and obvious
      difficulty in breathing. Blood oxygen saturation of 90%. The electrocardiogram
      showed: ST-T change,Tv6 flat;blood gas analysis: pH 7. 491, PCO2 34. 1 mmHg, PO2
      54. 7 mmHg; D-Dimer 3. 87 mg/L; white blood cell 17. 50 * 10(9)/L. CTPA showed:
      right pulmonary artery embolism,pulmonary infection. Another male patient with
      the right tonsil cancer accepted operation under general anesthesia. Fourth day
      of patient suddenly appear bosom frowsty and obvious difficulty in breathing.
      Blood oxygen sat- uration of 88%. Blood gas analysis: pH: 7. 48, PCO2 : 33 mmHg,
      PO2 : 57 mmHg; D-Dimer: 2. 97 mg/L; white blood cell:11. 80 * 10(9)/L. CTPA
      showed: the main pulmonary artery and right pulmonary artery branch embolism,
      pulmonary inflammation. Both were diagnosised as acute pulmonary embolism and
      recovered well after giving anticoagulant therapy in time.

PMID- 25989674
TI  - [One cases of scalp teratoma].
AB  - The patient, female, 27 years old. The scalp neoplasm had been found at her right
      temple 10 years ago. At first, the size of the tumor was just like a soybean, and
      did not grow obviously in the past nine and a half years. But the tumor increased
      fast in these six months, almost as large as the pigeon egg now. The physical
      examination showed that: A spherical tumor locates in the right temple near the
      right ear; the size of the tumor is 3 cm X 4 cm X 3 cm; the surface is smooth, no
      tenderness, no obvious mobile base, skull defect not touched. Primary diagnosis:
      the scalp cyst or lipoma. Under the local anesthesia we remove the neoplasm,
      during the operation we found the lesion located in the subcutaneous tissue
      layer, involved the galea aponeurosis layer, the skull surface are smooth and
      complete. The tumor was completely removed. We cut the mass and found a cystic
      cavity sized 3 cmX4 cm, which contained gray jerry-built materials, contained oil
      and a mass of hair, the capsule wall was complete. Postoperative pathological
      report: The tumor is cystic look throught the microscope, the capsule wall is
      squamous epithelium, containing keratinized material and hair. The pathological
      diagnosis is teratoma. The incision healed primarily, no recurrence found for
      about a year.

PMID- 25989675
TI  - [Giant tonsillolith in a child].
AB  - We describe a case of a 7-year-old child with Down syndrome who presented with
      loud snoring and cessation of breath during sleep and was found to have a large
      calculus (20 mm X 12 mm X 12 mm) in her left tonsil by CT scan for which
      tonsillectomy with adenoidectomy were done. This is one of the youngest reported
      cases in the literature.

PMID- 25989676
TI  - [Thyroglossal duct carcinoma combined with systemic lupus erythematosus: one case
      report].
AB  - Thyroglossal duct carcinoma is a malignant tumor which occurs in the thyroglossal
      duct cyst. The incidence of thyroglossal duct carcinoma has been reported as
      approximately 1%. Up to now, just about 250 cases of thyroglossal duct carcinoma
      have been reported in the literature,most of which are single case reports and
      small case series. In most cases, the diagnosis of the thyroglossal duct
      carcinoma is not made until the histologic examination after surgery operation.
      The preoperative examination such as CT or fine needle aspiration cytology can
      help the preoperative diagnosis. But the surgical treatment for the thyroglossal
      duct carcinoma is still controversial. Now we report a case of a thyroglossal
      duct carcinoma combined with systemic lupus erythematosus. The patient herself
      found an anterior neck mass in the median submental region one year ago. The
      preoperative CT examination suggested thyroglossal duct cyst with pouch
      canceration(papillary carcinoma). Then she underwent a Sistrunk procedure and
      level I neck dissection, and the histopathological diagnosis was thyroglossal
      duct carcinoma. The patient was treated with levothyroxine therapy at suppressive
      dose after the surgery. Now the patient is at regular follow-up with no relapse
      occur.

PMID- 25989677
TI  - [Research progress of squamous cell carcinoma of head and neck EGFR targeted
      therapy resistance mechanisms].
AB  - Overexpression of the epidermal growth factor receptor (EGFR) is a common
      characteristic of head and neck squamous cell carcinomas (HNSCC) , and initiates
      important signal transduction pathways in carcinogenesis. Now the EGFR is a
      validated target for cancer therapies in HNSCC. However, the effect of EGFR
      targeted therapies is only modest because of primary and/or acquired resistance.
      Therefore, an improved understanding of the molecular mechanisms of resistance to
      EGFR inhibitors may establish new treatment options to overcome resistance. In
      this review, the molecular mechanisms of resistance and the strategies to
      overcome it were summarized.

PMID- 25989678
TI  - [Application of 24-hour MII-pH monitoring in the diagnosis of laryngopharyngeal
      reflux disease].
AB  - Laryngopharyngeal reflux has become increasingly prevalent and received more and
      more attention. The "gold standard" for identifying and measuring
      laryngopharyngeal reflux disease is 24-hour multichannel intraluminal impedance
      pH monitoring. In this paper, we review the clinical application of this
      monitoring technology.

PMID- 25989679
TI  - [Thyroid operation after the discussion on drainage technology].
AB  - OBJECTIVE: To investigate the possibility of thyroidectomy/lobectomy without
      drainage after surgery. METHOD: Eighty-eight consecutive cases with thyroid mass
      have been underwent operations including: lobectomy group(42 cases), thyroid
      lobectomy with contralateral partial thyroidectomy group (17 cases) and total
      thyroidectomy group (29 cases) from 2013. 06 to 2014. 06 in Nanjing Tongren
      Hospital. FIfteen patients with thyroid operation in other hospital were
      collected from 2014. 01 to 2014. 06, the recovery of postoperative incision were
      compared. RESULTS: Eighty-four cases were smoothly discharged from hospital
      except 4 thyroidectomy cases suffered from a small amount of effusion in surgical
      cavity. Our postoperative wound recovery were more in line with the principle of
      cosmetology compared with other hospital operation group. CONCLUSION: Drainage
      following thyroidectomy is not essential, if the thyroid surgery is meticulous in
      each step of the surgery, and can increase the effect of beauty.

PMID- 25989680
TI  - [Recent developments of dispersive liquid-liquid microextraction technique].
AB  - As a relatively new sample preparation technique, dispersive liquid-liquid
      microextraction (DLLME) has the advantages of simplicity of operation, high
      enrichment factor and low consumption of organic solvent. In this review, the
      recent advances of DLLME and its important applications are briefly reviewed,
      including (1) the combined use of DLLME with other extraction methods, (2) the
      expansion of the extraction solvent, (3) the development of extraction devices.

PMID- 25989681
TI  - [Isotopic tracing technique in quantitative analysis of metabolic reprogramming
      in tumor cells].
AB  - It is hard to begin to discuss tumor metabolism without mentioning Warburg
      effect. Tumor metabolism has been received intensive attention in recent years
      for understanding Warburg effect which is also known as aerobic glycolysis. Even
      Warburg did not anticipate, other nutrients, such as glutamine, serine and
      glycine could serve as alternative source for energy demands and block building
      in cancer cells. To delineate altered metabolic pathways in cancer cells,
      isotopic tracing technique provides a novel and holistic insight in metabolic
      switch under control of oncogenes and tumor suppressor genes. An array of
      chromatography coupled with mass spectrometry is the powerful tool to detect the
      isotope-labeled metabolites for unlocking the underlying biochemical reactions in
      cancer cells. In this review article, we focus on carbon-13 and deuterium
      labeling for quantitative analysis of intermediate metabolites including reduced
      form of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is mainly
      derived from pentose phosphate pathway in previous biochemical textbook. However,
      deuterium-isotope labeling metabolic flux analysis can reveal other important
      pathways for NADPH production, such as one-carbon metabolism, which is also
      discussed in this review.

PMID- 25989682
TI  - [Preparation of grapheme oxide based immobilized lectin and its application to
      efficient glycoprotein/glycopeptide enrichment].
AB  - Protein glycosylation in eukaryotic cells regulates a variety of physiological
      processes including cell recognition, cell adhesion, migration, and immune
      response. It is also closely related with the occurrence and development of many
      critical diseases. Therefore, large scale identification of protein glycosylation
      not only provides important information for the study of basic biological
      mechanisms, but also is crucial for the discovery of new diagnostic biomarkers
      and therapeutic targets. Due to the low abundance of glycoprotein/glycopeptide in
      real biological samples, enrichment before mass spectrometry (MS) analysis is an
      essential step for achieving deep glycosylation site coverage. Lectin enrichment,
      as an effective method for glycoproteins/glycopeptides enrichment, has been
      utilized widely in glycoproteomics research. To solve the problems of low lectin
      loading and limited enrichment efficiency of existing lectin functional
      materials, we prepared two kinds of new graphene oxide ( GO) immobilized lectin.
      Besides good dispersion in aqueous solution as well as good chemical stability,
      GO has extremely large specific surface area and also carries high density of
      functional groups on its surface, which is especially benelicial for achieving
      high lectin loading amount. As a result, lectin loading as high as 1. 90 mg/mg
      was achieved for GO-lectin (GO-ConA 2. 073 mg/mg, RSD = 1. 0%; GO-WGA 1. 908
      mg/mg, RSD = 0.14%). One milligram GO-lectin can adsorb more than 200 ug
      glycoprotein each experiment in two weeks. The GO-lectin was successfully applied
      in glycoproteins/glycopeptides enrichment with high efficiency and selectivity,
      indicating its good application potential in glycoproteomics research.

PMID- 25989683
TI  - [Rapid fabrication of molecularly imprinted polymer fibers for solid phase
      microextraction of bisphenol A].
AB  - The rapid preparation of molecularly imprinted polymer (MIP) fibers was reported
      using bisphenol A (BPA) as the template molecular, acetonitrile (ACN) as the
      porogenic solvent, alpha-methacrylic acid (MAA) as the functional monomer,
      ethylene dimethacrylate (EDMA) as the crosslinker, and azodiisobutyronitrile
      (AIBN) as the thermal initiator. It was carried out within a capillary of 530 um
      inner diameter (I. D.) by microwave irradiation in 7 min. The resulted BPA-MIP
      fibers were pushed out from the capillary, eluted in a vial and inserted in the
      capillary again followed by the application of the solid phase microextraction
      (SPME) procedure. The extraction performance was investigated in detail by
      varying the molar ratios between the template and the monomer (BPA/MAA), the
      concentration of NaCl, the extraction and desorption time, the pH value and the
      desorption solvents. The selectivity of the prepared MIP and non-molecularly
      imprinted polymer (NIP) fibers was comparatively evaluated by selecting two
      structurally-related compounds, phenol (P) and 4-phenylphenol (PP), and non
      analogue dicyandiamide (DCD). The established method was successfully applied for
      the pretreatment and determination of BPA from beverage samples coupled to high
      performance liquid chromatography (HPLC). Under the optimal conditions, the
      linear range of BPA was 10-400 ug/L; the detection limit (LOD) was 0.45 ug/L and
      the recoveries spiked in the mineral water were 88.4%-102. 8%. The results
      demonstrated that the developed method can determine BPA in real samples with
      some advantages of simple pretreatment, rapid analysis, low limit of detection
      and low consumption of materials.

PMID- 25989684
TI  - [Multi-residue determination of veterinary drugs in cheese by QuEChERS and liquid
      chromatography-tandem mass spectrometry].
AB  - A rapid and sensitive method has been developed for the simultaneous
      determination of 50 veterinary drugs (including macrolides, quinolones,
      sulfonamides, and tetracyclines) in cheese using a modified QuEChERS method
      coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). After
      adding Na2EDTA buffer solution and ceramic homogenizer, the cheese sample was
      extracted by 5% (v/v) acetic acid-acetonitrile, sodium chloride and anhydrous
      sodium sulfate were used for salting-out process. The resulting supernatant
      solution was purified by C18 sorbent and the re-dissolved solution was analyzed
      by LC-MS/MS under dynamic multi-reaction monitoring (dynamic MRM) mode via
      positive electrospray ionization with a ZORBAX-SB-C18 column. The limits of
      quantification (LOQ, S/N= 10) of the target compounds ranged from 0. 05 ug/kg to
      20 ug/kg in cheese. At spiked levels of 20, 50, 100 ug/kg (n =6) , the
      percentages of drug with a recovery between 70% and 120% were 94%, 92%, and 96%,
      respectively. The relative standard deviations (RSDs) were between 1% and 14%.
      This method has been applied to determine seven real samples from markets.
      Roxithromycin and flumequine have been detected in two samples separately. The
      results demonstrated that this simple, rapid and accurate method is suitable for
      the detection of multi-class veterinary drugs in cheese.

PMID- 25989685
TI  - [Regression evaluation index intelligent filter method for quick optimization of
      chromatographic separation conditions].
AB  - This paper presents a method of regression evaluation index intelligent filter
      method (REIFM) for quick optimization of chromatographic separation conditions.
      The hierarchical chromatography response function was used as the chromatography
      optimization index. The regression model was established by orthogonal regression
      design. The chromatography-optimization index was filtered by the intelligent
      filter program, and the optimization of the separation conditions was obtained.
      The experimental results showed that the average relative deviation between the
      experimental values and the predicted values was 0. 18% at the optimum and the
      optimization results were satisfactory.

PMID- 25989686
TI  - [Application of gas chromatography-high resolution quadrupole time of flight mass
      spectrometry to the analysis of benzaldehyde, benzyl alcohol acetophenone and
      phenylacetaldehyde in complex aromatic samples].
AB  - The study focuses on the quantitative analytical characterization of
      benzaldehyde, benzyl alcohol, acetophenone and phenylacetaldehyde in complex
      aromatic samples by gas chromatography-high resolution quadrupole time of flight
      mass spectrometry (GC-QTOF MS). The four compounds in real sample were accurately
      qualified and quantified through a comprehensive analysis of the GC retention
      times and the accurate masses of the ion fragments obtained by the high
      resolution MS. The new method therefore effectively avoids the interference of
      the real sample substrate, which reduces the accuracy of the analysis results.
      The peak area of the characteristic ion fragment for each compound was used for
      quantitation calculation. The MS signal responses of the four compounds showed
      good linear relationships with the corresponding mass concentrations and the
      linear regression coefficients were greater than 0. 99. The method recoveries
      were 87. 97% - 103.01%. The limits of detection (LODs) were 0. 01, 0. 03, 0. 02
      and 0. 01 mg/L for benzaldehyde, benzyl alcohol, acetophenone and
      phenylacetaldehyde respectively. The contents of the four compounds in three real
      samples were analyzed. The study provided a new strategy for oxygenate analysis
      in complex aromatic samples using GC-QTOF MS. By measuring the accurate masses,
      the new method reduces the reliance on chromatographic separation ability and
      makes up the shortcomings of the traditional GC-MS methods.

PMID- 25989687
TI  - [Determination of gambogic acid in Gamboge by non-aqueous capillary
      electrophoresis].
AB  - Gambogic acid (GA), a kind of caged xanthones, has low solubility in water. A non
      aqueous capillary electrophoresis (NACE) was established for the determination of
      GA in Gamboge based on the optimized conditions. The effect of 20% - 60% methanol
      or acetonitrile spiked in running solution was investigated. The effects of
      compositions, concentration, pH, additives like beta-cyclodextrin in running
      buffer were thoroughly studied. Applied voltage and applied temperature were also
      observed. Optimal electrophoretic conditions were as follows: 20 mmol/L sodium
      borohydride solution (pH 9. 86) containing 40% (v/v) acetonitrile, 10 mmol/L beta
      cyclodextrin as running buffer, applied voltage of 10 kV, capillary temperature
      of 30  degrees C and detection wavelength of 280 nm. The calibration curve had
      good linearity in the range of 2-2 000 mg/L with the correlation coefficient of
      0. 999 6. The limit of quantification (S/N= 3) of the method was 2 mg/L. The
      quantifications of GA in Gamboge from different producing places including
      Vietnam, Thailand, Burma, India were 1. 67-472.40 mg/g with the RSD (n= 3) of
      1.12% -2.60%. The content of Gamboge from Vietnam is obviously low while the
      others are high. The recoveries of GA spiked in real samples ranged from 95. 2%
      to 105. 6%. The method of NACE is simple, efficient and of good reproducibility,
      can be served as a novel reference to identify and control the quality of
      Gamboge.

PMID- 25989688
TI  - [Determination of fluorescent whitening agents in disposable sanitary products by
      high performance liquid chromatography].
AB  - A method for the determination of four fluorescent whitening agents (FWAs) (FWA
      357, FWA 220, FWA 204 and FWA 113) in disposable sanitary products by high
      performance liquid chromatography with diode array detection (HPLC-DAD) was
      developed. The sample was extracted with a 20 mL ultrapure water by sonication
      for 30 min at 80  degrees C. The HPLC method was performed on an SB Phenyl column
      (250 mm x 4. 6 mm, 5 um) by gradient elution using 5 mmol/L ammonium acetate and
      acetonitrile as mobile phases, which can separate the target analytes
      successfully. The target analytes showed good linearity in the range of 0. 025
      400 mg/L with the correlation coefficients (r2) greater than 0. 999 9. The limits
      of detection (LODs, S/N =3) were 0.02-0. 1 mg/L, and the method limits of
      quantification (MLOQs) were 1. 0 - 5. 0 mg/kg for the target analytes. The
      feasibility of this method was demonstrated by the determination of FWAs in
      samples with spiked recoveries. The recoveries were in the range between 83. 7%
      and 101. 0%, and the relative standard deviations (RSDs) (n=6) ranged from 2. 4%
      to 7. 0%. This method is simple, and has high recoveries for the determination of
      FWAs in disposable sanitary products.

PMID- 25989689
TI  - [Simultaneous determination of three inorganic anions in food-grade lubricating
      oils by chromatography with suppressed conductivity detection].
AB  - An ion chromatographic (IC) method with suppressed conductivity detection was
      developed for the simultaneous determination of Cl-, NO3(-), SO(2-)(4) in food
      grade lubricating oils. After ultrasonic extraction with 50% (v/v) methanol
      aqueous solution and centrifugation, the sample in aqueous phase was purified
      with 0. 22 um hybrid fiber membranes, then analyzed by IC using 15 mmol/L KOH
      solution as eluent, and detected by a suppressed conductivity detector. Effects
      of the concentration and flow rate of the eluent, and the concentration of the
      methanol aqueous solution on the detection of the three anions were investigated.
      Under the optimized separation conditions, the three anions were separated
      completely and the system peaks didn't interfere with the determination. The
      calibration curves showed good linearity (R2> 0. 999) in the range of 0. 10-20.
      00 mg/L. The limits of detection (LODs, S/N= 3) were 0. 01 - 0. 03 mg/kg. The
      average recoveries of Cl-, NO(-)3, SO(2-)4 anions were 90. 0% - 103. 6% with the
      relative standard deviations (RSDs) of 2. 8% - 5. 7%. This method avoids the time
      consuming pretreatment process to burn or ash the oil phase matrix, and can
      determine the amounts of three inorganic anions (Cl-, NO(-)3, SO(2-)(4)) in food
      grade lubricating oils fast and accurately. It is suitable for simultaneously
      separating and detecting trace inorganic anions in lubricating oils or other oil
      products.

PMID- 25989690
TI  - [Simultaneous determination of five active components of compound alpha-ketoacid
      tablet in human urine by ion-pair reversed-phase high performance liquid
      chromatography].
AB  - A simple and sensitive method for the simultaneous determination of five active
      components, D, L-alpha-hydroxymethionine calcium (HMACa), alpha-ketovaline
      calcium (KVCa), D, L-alpha-ketoisoleucine calcium (KILCa), alpha-ketoleucine
      calcium (KLCa) and alpha-ketophenylalanine calcium (KPACa) of compound alpha
      ketoacid tablet in human urine by ion-pair reversed-phase high performance liquid
      chromatography (RP-HPLC) was developed and validated. The separation conditions,
      such as the concentration of ion-pair reagent, the pH value of the mobile phase
      and the concentration of the buffer were optimized. All the five analytes were
      separated well on a C18 column (250 mm x 4.6 mm, 5 um) with diode array detection
      at 210 nm and the column temperature of 35  degrees C. The mobile phases were
      acetonitrile and 20 mmol/L phosphate buffer (containing 15 mmol/L
      tetrabutylammonium hydroxide; pH 7) at the flow rate of 1. 0 mL/min with gradient
      elution. The calibration curves for the five components were linear in the range
      from 20 to 200 mg/L (r>= 0. 9990). The limits of detection (LODs, S/N= 3) were
      3.0, 5. 0, 3. 6, 5.7 and 2. 5 mg/L, and the limits of quantification (LOQs, S/N=
      10) were 9. 6, 16.7, 12.0, 19.0 and 8.3 mg/L for HMACa, KVCa, KILCa, KLCa and
      KPACa, respectively. The intra-day and inter-day precisions were less than 7%,
      and the average recoveries were between 86.79% and 112. 00% in the human urine
      with RSDs lower than 9% (n= 5). The method proved precise, specific and
      reproducible, and can be used for the determination of the five components in
      urine.

PMID- 25989691
TI  - [Analysis of the volatile components in Minnan oolong tea by headspace solid
      phase microextraction coupled with comprehensive two-dimensional gas
      chromatography-time of flight mass spectrometry and the application in its
      variety identification].
AB  - A method to analyze the volatile components in Minnan oolong tea was developed
      based on headspace solid phase microextraction (HS-SPME) coupled with
      comprehensive two-dimensional gas chromatography-time of flight mass spectrometry
      (GC*GC-TOF MS). Volatile compounds of 48 oolong tea samples with different
      qualities and production seasons from five varieties (Tieguanyin, Huangjingui,
      Benshan, Maoxie and Meizhan) were extracted by HS-SPME and analyzed by GC*GC-TOF
      MS. More than 2 000 peaks were obtained from each sample, and 51 common compounds
      were tentatively identified by comparison with the standard mass spectrum
      databases, retention indices and structure spectra. The projection score of the
      common compounds obtained from principal component analysis ( PCA) had presented
      a straightforward classification trend for different oolong tea varieties. In
      addition, 9 compounds which had significant impact on the classification were
      selected by stepwise discriminate analysis, and used as variables to establish
      four discriminated functions by Fisher's discriminate analysis (FDA). The
      accuracy for the recognition of 48 samples was 97. 9%. The results had
      demonstrated the feasibility of the method to be used to discriminate the oolong
      tea varieties.

PMID- 25989692
TI  - [Determination of short chain chlorinated paraffins in polyvinyl chloride
      plastics by gas chromatography-negative chemical ion/mass spectrometry].
AB  - A novel method was established to determine short chain chlorinated paraffins (SC
      CPs) in polyvinyl chloride (PVC) plastics by gas chromatography-negative chemical
      ion/mass spectrometry (GC-NCI/MS). Ultrasonic extraction was used to extract
      SCCPs from PVC plastics. The optimal extraction time was 1.5 h, and concentrated
      sulfuric acid was adopted to purify the extracted solution. Finally, SCCPs in a
      sample were detected by GC-NCI/MS at 160 C and with methane reagent gas at 1. 5
      mL/min. This method was not influenced by medium chain chlorinated paraffins
      (MCCPs) in the sample, and accurate quantitation was made for SCCPs. Twelve
      batches of samples were analyzed and SCCPs were detected in each batch with the
      contents from 0. 3 x 10(2)mg/kg to 3. 5 x 10(4)mg/kg. With respect to European
      limitation of SC-CPs (1%), four batches of samples did not comply with the
      European regulation, and they accounted for 33. 3%. Obviously, high SCCPs risk
      was presented in PVC plastics.

PMID- 25989693
TI  - [Coupling of gas chromatography with single photon ionization time-of-flight mass
      spectrometry and its application to characterization of compounds in diesel].
AB  - A novel analytical method coupling gas chromatography (GC) with single photon
      ionization time-of-flight mass spectrometry (SPI-TOF MS) has been developed.
      First of all, a double-wall-tube transfer line was built to combine GC with SPI
      TOF MS, which realized seamless connection between GC and SPI ion source. Based
      on this, standard n-pentadecane and benzene/toluene/xylene standard gas mixtures
      were used to study important voltage parameters of the ion source. After the
      optimization of the ion source voltages, pure molecular ion peaks of the analytes
      were obtained in the mass spectra and qualitative analysis of different kinds of
      organic compounds were eventually realized rapidly and accurately. At last,
      GC/SPI-TOF MS was applied to the characterization of volatile and semvolatile
      organic compounds in diesel and two-dimensional spectra of GC*SPI-TOF MS were
      obtained. Without complicated spectra interpretation and data processing,
      volatile and semi-volatile organic compounds in diesel have been classified
      qualitatively by ion mass-to-charge ratio (m/z) in SPI mass spectra, including
      aliphatic compounds, aromatic compounds and nitrogen-containing compounds with
      low concentration such as benzopyrroles. Isomeric compounds in diesel were
      separated and identified by retention times of chromatographic peaks. The results
      indicate that the proposed analytical method of GC/SPI-TOF MS is suitable for the
      characterization of complicated samples such as diesel and environmental
      pollutants with easy operation and high efficiency.

PMID- 25989694
TI  - [Determination of the four generic fractions of aged bitumen by thin-layer
      chromatography with flame ionization detection].
AB  - The aging process of bitumen has been paid more and more attention by the
      researchers. The four generic fractions (saturates, aromatics, resins and
      asphaltenes) of bitumen change significantly during the aging process. The
      analysis of the changes of the four generic fractions of bitumen is very helpful
      to reveal the bitumen aging mechanisms and guide its engineering applications. In
      this study, the bitumen was aged by thin film oven test (TFOT) , pressurized
      aging vessel (PAV) test and ultraviolet (UV) aging test, respectively. Then the
      four generic fractions of bitumen before and after aging were analyzed by thin
      layer chromatography with flame ionization detection (TLC-FID) , which was
      further compared with the solubility procedures and chromatographic technique (
      named as Corbett method). The compositions of the expanded solvents were also
      investigated. Finally, the correlation between the TLC-FID and Corbett method was
      further studied, which revealed a proper TLC-FID meth- od for detection of aged
      bitumen. The bitumen solution dissolved by dichloromethane was successively
      expanded by n-heptane, toluene/n-heptane (80 :20, v/v) and toluene/ethanol (55:
      45, v/v) , followed by TLC-FID. This method is of great significance for the
      analysis of the four generic fractions of bitumen and for the exploration of
      bitumen aging mechanisms.

PMID- 25989695
TI  - [Analysis of difference of serum proteins between patients with cirrhosis and
      normal people by capillary electrophoresis with light-emitting diode induced
      fluorescence detection].
AB  - An experimental method of protein separation by capillary electrophoresis coupled
      with light-emitting diode induced fluorescence detection (CE-LED-IF) was
      established. The fluorescein isothiocyanate (FITC) was used as fluorescent dye in
      this method. An optical fiber was inserted into the separation capillary and was
      suited right at the detection window which was used to transmit the excitation
      light of LED. The efficiency of the light of LED and the detection limits of FITC
      was improved. The difference of serum proteins between the patients with
      cirrhosis and normal people was detected by this method. A series of effects on
      CE were studied, such as the wavelength of the light source and filter, the
      concentration and pH of the running buffer and the separation voltage. Then the
      optimized method was established for the determination of the serum proteins. The
      repeatability of CE-LED-IF was tested and the RSDs of migration time and peak
      area were 1. 14% and 3. 23% , respectively. The results showed that there were
      two specific peaks in cirrhosis serum. The differences between the patients with
      cirrhosis and normal people having statistical significance indicated that these
      proteins might be the potential biomarkers for cirrhosis diagnosis. The developed
      CE-LED-IF method proved suitable for the separation of serum proteins with good
      repeatability and supportable for the clinical diagnosis of cirrhosis.

PMID- 25989696
TI  - Is there a difference in post-transplant lymphoproliferative disorder in adults
      after solid organ and haematologic stem cell transplantation? Experience in 41
      patients.
AB  - OBJECTIVE: To determine if there is a difference in post-transplant
      lymphoproliferative disorder (PTLD) in adults after solid organ transplantation
      (SOT) and haematologic stem cell transplantation (HST). METHODS: In this
      institutional review board-approved Health Insurance Portability and
      Accountability Act-compliant study, we reviewed clinical data and imaging at the
      time of diagnosis in 41 patients (26 SOT and 15 HST) (31 males and 10 females;
      mean age 51 years) with histopathology-confirmed PTLD seen at our institution
      from 2004 through 2013. Statistical analysis was performed to assess difference
      in distribution and survival between SOT and HST cohorts. RESULTS: SOT: 17
      lung/cardiac, 8 renal and 1 liver transplant recipients. HST: 13
      leukaemia/lymphoma and 2 patients with aplastic anaemia. Median time to
      diagnosis: SOT 3.0 years; HST 6 months (Fisher's exact test; p = 0.0011). There
      was no statistically significant difference in distribution of PTLD after SOT and
      HST with nodes (15/26; 8/15), lung (10/26; 5/15) and bowel (6/26; 4/15) being the
      most common sites. Hepatic (3/26) and neurologic (2/26) involvement occurred in
      only SOT cohort while splenic PTLD (5/15) occurred more often in HST cohort.
      Death occurred earlier in HST (9/15; 2 weeks) than SOT cohort (12/26; 11 months)
      (Wilcoxon test; p = 0.0188). CONCLUSION: PTLD did not differ significantly in
      distribution between SOT and HST cohorts. PTLD after HST occurred early and had
      shorter survival. ADVANCES IN KNOWLEDGE: The most common sites of PTLD were the
      nodes, lung and bowel. Distribution of PTLD does not differ significantly between
      patients with SOT and HST. PTLD after HST occurs early and has poor survival
      compared with PTLD after SOT.

PMID- 25989698
TI  - Benefits of fluorine-18 fludeoxyglucose positron emission tomography in secondary
      cytoreductive surgery for patients with recurrent epithelial ovarian cancer.
AB  - OBJECTIVE: To investigate the benefits of fluorine-18 fludeoxyglucose positron
      emission tomography ((18)F-FDG-PET) in patients undergoing secondary
      cytoreductive surgery (SCRS) for recurrent epithelial ovarian cancer. METHODS:
      Patients were identified, and their clinical information was extracted by review
      of the gynaecologic oncology database of Peking Union Medical College Hospital.
      (18)F-FDG-PET scan and analysis were performed by nuclear medicine experts at our
      hospital. RESULTS: The PET group and the control group of patients evaluated by
      conventional imaging methods differed significantly with respect to the
      proportion of patients who underwent complete SCRS and the number of residual
      lesions (p = 0.002 and 0.006, respectively). A Cox model showed that longer
      progression-free survival (PFS) correlated significantly with (18)F-FDG-PET
      evaluation [relative risk (RR) = 0.432; p = 0.001], sensitivity to platinum-based
      chemotherapies (RR = 0.604; p = 0.034) and resection completeness (RR = 0.679; p
      = 0.039). Longer overall survival (OS) correlated significantly with sensitivity
      to platinum-based chemotherapy (RR = 0.317; p = 0.000) and the CA-125 level after
      two cycles of chemotherapy (RR = 2.663; p = 0.003). Surgical safety and
      complications did not significantly differ between the two groups of patients.
      CONCLUSION: (18)F-FDG-PET is useful for evaluating patients with recurrent
      epithelial ovarian carcinoma. Patients who undergo PET-guided SCRS have a greater
      chance of complete tumour resection and a longer PFS. ADVANCES IN KNOWLEDGE: SCRS
      guided by PET results in fewer residual lesions. PET-guided SCRS is safe and can
      prolong PFS and OS in patients with recurrent ovarian cancer.

PMID- 25989699
TI  - Monitoring proton therapy with PET.
AB  - Protons are being used in radiation therapy because of typically better dose
      conformity and reduced total energy deposited in the patient as compared with
      photon techniques. Both aspects are related to the finite range of a proton beam.
      The finite range also allows advanced dose shaping. These benefits can only be
      fully utilized if the end of range can be predicted accurately in the patient.
      The prediction of the range in tissue is associated with considerable
      uncertainties owing to imaging, patient set-up, beam delivery, interfractional
      changes in patient anatomy and dose calculation. Consequently, a significant
      range (of the order of several millimetres) is added to the prescribed range in
      order to ensure tumour coverage. Thus, reducing range uncertainties would allow a
      reduction of the treatment volume and reduce dose to potential organs at risk. 

PMID- 25989697
TI  - Personalized radiotherapy: concepts, biomarkers and trial design.
AB  - In the past decade, and pointing onwards to the immediate future, clinical
      radiotherapy has undergone considerable developments, essentially including
      technological advances to sculpt radiation delivery, the demonstration of the
      benefit of adding concomitant cytotoxic agents to radiotherapy for a range of
      tumour types and, intriguingly, the increasing integration of targeted
      therapeutics for biological optimization of radiation effects. Recent molecular
      and imaging insights into radiobiology will provide a unique opportunity for
      rational patient treatment, enabling the parallel design of next-generation
      trials that formally examine the therapeutic outcome of adding targeted drugs to
      radiation, together with the critically important assessment of radiation volume
      and dose-limiting treatment toxicities. In considering the use of systemic agents
      with presumed radiosensitizing activity, this may also include the identification
      of molecular, metabolic and imaging markers of treatment response and
      tolerability, and will need particular attention on patient eligibility. In
      addition to providing an overview of clinical biomarker studies relevant for
      personalized radiotherapy, this communication will highlight principles in
      addressing clinical evaluation of combined-modality-targeted therapeutics and
      radiation. The increasing number of translational studies that bridge large-scale
      omics sciences with quality-assured phenomics end points-given the imperative
      development of open-source data repositories to allow investigators the access to
      the complex data sets-will enable radiation oncology to continue to position
      itself with the highest level of evidence within existing clinical practice. 

PMID- 25989700
TI  - Rapamycin ameliorates the CTLA4-Ig-mediated defect in CD8(+) T cell immunity
      during gammaherpesvirus infection.
AB  - Latent viral infections are a major concern among immunosuppressed transplant
      patients. During clinical trials with belatacept, a CTLA4-Ig fusion protein,
      patients showed an increased risk of Epstein-Barr virus-associated posttransplant
      lymphoproliferative disorder, thought to be due to a deficient primary CD8(+) T
      cell response to the virus. Using a murine model of latent viral infection, we
      observed that rapamycin treatment alone led to a significant increase in virus
      specific CD8(+) T cells, as well as increased functionality of these cells,
      including the ability to make multiple cytokines, while CTLA4-Ig treatment alone
      significantly dampened the response and inhibited the generation of
      polyfunctional antigen-specific CD8(+) T cells. However, the addition of
      rapamycin to the CTLA4-Ig regimen was able to quantitatively and qualitatively
      restore the antigen-specific CD8(+) T cell response to the virus. This
      improvement was physiologically relevant, in that CTLA4-Ig treated animals
      exhibited a greater viral burden following infection that was reduced to levels
      observed in untreated immunocompetent animals by the addition of rapamycin. These
      results reveal that modulation of T cell differentiation though inhibition of
      mTOR signaling can restore virus-specific immune competence even in the absence
      of CD28 costimulation, and have implications for improving protective immunity in
      transplant recipients. 

PMID- 25989702
TI  - Dynamic evolution of Geranium mitochondrial genomes through multiple horizontal
      and intracellular gene transfers.
AB  - The exchange of genetic material between cellular organelles through
      intracellular gene transfer (IGT) or between species by horizontal gene transfer
      (HGT) has played an important role in plant mitochondrial genome evolution. The
      mitochondrial genomes of Geraniaceae display a number of unusual phenomena
      including highly accelerated rates of synonymous substitutions, extensive gene
      loss and reduction in RNA editing. Mitochondrial DNA sequences assembled for 17
      species of Geranium revealed substantial reduction in gene and intron content
      relative to the ancestor of the Geranium lineage. Comparative analyses of nuclear
      transcriptome data suggest that a number of these sequences have been
      functionally relocated to the nucleus via IGT. Evidence for rampant HGT was
      detected in several Geranium species containing foreign organellar DNA from
      diverse eudicots, including many transfers from parasitic plants. One lineage has
      experienced multiple, independent HGT episodes, many of which occurred within the
      past 5.5 Myr. Both duplicative and recapture HGT were documented in Geranium
      lineages. The mitochondrial genome of Geranium brycei contains at least four
      independent HGT tracts that are absent in its nearest relative. Furthermore, G.
      brycei mitochondria carry two copies of the cox1 gene that differ in intron
      content, providing insight into contrasting hypotheses on cox1 intron evolution. 

PMID- 25989701
TI  - Individualized home-based exercise programs for older people to reduce falls and
      improve physical performance: A systematic review and meta-analysis.
AB  - There is considerable diversity in the types of exercise programs investigated to
      reduce falls in older people. The purpose of this paper was to review the
      effectiveness of individualized (tailored) home-based exercise programs in
      reducing falls and improving physical performance among older people living in
      the community. A systematic review and meta-analysis was conducted of randomized
      or quasi-randomized trials that utilized an individualized home-based exercise
      program with at least one falls outcome measure reported. Single intervention
      exercise studies, and multifactorial interventions where results for an exercise
      intervention were reported independently were included. Two researchers
      independently rated the quality of each included study. Of 16,871 papers
      identified from six databases, 12 met all inclusion criteria (11 randomized
      trials and a pragmatic trial). Study quality overall was high. Sample sizes
      ranged from 40 to 981, participants had an average age 80.1 years, and although
      the majority of studies targeted the general older population, several studies
      included clinical groups as their target (Parkinson's disease, Alzheimer's
      disease, and hip fracture). The meta-analysis results for the five studies
      reporting number of fallers found no significant effect of the intervention (RR
      [95% CI]=0.93 [0.72-1.21]), although when a sensitivity analysis was performed
      with one study of participants recently discharged from hospital removed, this
      result was significant (RR [95% CI] = 0.84 [0.72-0.99]). The meta-analysis also
      found that intervention led to significant improvements in physical activity,
      balance, mobility and muscle strength. There were no significant differences for
      measures of injurious falls or fractures. 

PMID- 25989703
TI  - IMPLICATIONS OF GLOBAL PRICING POLICIES ON ACCESS TO INNOVATIVE DRUGS: THE CASE
      OF TRASTUZUMAB IN SEVEN LATIN AMERICAN COUNTRIES.
AB  - OBJECTIVES: Differential pricing, based on countries' purchasing power, is
      recommended by the World Health Organization to secure affordable medicines.
      However, in developing countries innovative drugs often have similar or even
      higher prices than in high-income countries. We evaluated the potential
      implications of trastuzumab global pricing policies in terms of cost
      effectiveness (CE), coverage, and accessibility for patients with breast cancer
      in Latin America (LA). METHODS: A Markov model was designed to estimate life
      years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare
      perspective. To better fit local cancer prognosis, a base case scenario using
      transition probabilities from clinical trials was complemented with two
      alternative scenarios with transition probabilities adjusted to reflect breast
      cancer epidemiology in each country. RESULTS: Incremental discounted benefits
      ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from
      USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross
      domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in
      Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that
      trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and
      remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent
      and 26.6 percent, respectively). Trastuzumab price would need to decrease between
      69.6 percent to 94.9 percent to became CE in LA. CONCLUSIONS: Although CE in
      other settings, trastuzumab was not CE in LA. The use of health technology
      assessment to prioritize resource allocation and support price negotiations is
      critical to making innovative drugs available and affordable in developing
      countries.

PMID- 25989704
TI  - Preschool Program Improves Young Children's Food Literacy and Attitudes to
      Vegetables.

PMID- 25989705
TI  - DNA barcoding of common soft scales (Hemiptera: Coccoidea: Coccidae) in China.
AB  - The soft scales (Hemiptera: Coccoidea: Coccidae) are a group of sap-sucking plant
      parasites, many of which are notorious agricultural pests. The quarantine and
      economic importance of soft scales necessitates rapid and reliable identification
      of these taxa. Nucleotide sequences of the mitochondrial cytochrome c oxidase
      subunit I (COI) gene (barcoding region) and 28S rDNA were generated from 340
      individuals of 36 common soft scales in China. Distance-based [(best match,
      Automated Barcode Gap Discovery (ABGD)], tree-based (neighbor-joining, Bayesian
      inference), Klee diagrams, and general mixed Yule coalescent (GMYC) models were
      used to evaluate barcoding success rates in the data set. Best match showed that
      COI and 28S sequences could provide 100 and 95.52% correct identification,
      respectively. The average interspecific divergences were 19.81% for COI data and
      20.38% for 28S data, and mean intraspecific divergences were 0.56 and 0.07%,
      respectively. For COI data, multiple methods (ABGD, Klee, and tree-based methods)
      resulted in general congruence with morphological identifications. However, GMYC
      analysis tended to provide more molecular operational taxonomic units (MOTUs).
      Twelve MOTUs derived from five morphospecies (Rhodococcus sariuoni, Pulvinaria
      vitis, Pulvinaria aurantii, Parasaissetia nigra, and Ceroplastes rubens) were
      observed using the GMYC approach. In addition, tree-based methods showed that 28S
      sequences could be used for species-level identification (except for Ceroplastes
      ceriferus - Ceroplastes pseudoceriferus), even with low genetic variation (<1%).
      This report demonstrates the robustness of DNA barcoding for species
      discrimination of soft scales with two molecular markers (COI and 28S) and
      provides a reliable barcode library and rapid diagnostic tool for common soft
      scales in China.

PMID- 25989708
TI  - Is it useful to ask "Esta deprimido?" ("Are you depressed?") to terminally-ill
      Portuguese patients? Results from outpatient research.
AB  - OBJECTIVES: Depression is a serious psychological problem in the palliative care
      setting. Brief screening tools for depression are lacking and need to be brief
      and acceptable. This study aimed to identify the properties of the single
      Portuguese question "Esta deprimido?" ("Are you depressed?") to screen for
      depression. METHODS: Retrospective study from 100 patient's medical records
      identifying the answers on the single Portuguese question for depression "Esta
      deprimido?" ("Are you depressed?") and the HADS depression sub-scale, using a
      score >=11 on the latter as the gold standard for clinically significant
      depressive symptoms. Sensitivity, specificity, positive predictive and negative
      values were calculated. RESULTS: Response rate for the single Portuguese question
      for depression was 100%. Prevalence of depression symptoms (HADS-d >= 11) was
      43%. To the question "Esta deprimido?" 60 patients responded "yes." Sixteen
      patients who replied "no" to the single question had clinically significant
      depressive symptoms based on the HADS depression sub-scale. The single tool had
      65.2% sensitivity, 49.2% specificity and 50.0% and 64.4% of positive predictive
      and negative values, respectively. SIGNIFICANCE OF RESULTS: In this first
      preliminary retrospective Portuguese study, the single question for depression
      has shown poor screening properties. Future research in larger and mixed patients
      samples of Portuguese terminally ill is necessary to find more accurate and
      robust properties of this brief tool.

PMID- 25989706
TI  - Comparative study of combined bevacizumab/targeted photocoagulation vs
      bevacizumab alone for macular oedema in ischaemic branch retinal vein occlusions.
AB  - PURPOSE: To investigate whether targeted retinal photocoagulation (TRP) of
      peripheral non-perfused areas (NPAs) could prevent the recurrence of macular
      oedema (ME) due to branch retinal vein occlusion (BRVO) after intravitreal
      bevacizumab injection (IVB). METHODS: Eyes received 1.25 mg IVB only (IVB group)
      or combined with TRP (IVB + TRP group) of NPAs, more than 5 disc areas identified
      by fluorescein angiography in the patients with ME secondary to BRVO. Best
      corrected visual acuity (BCVA) and central retinal thickness (CRT) determined by
      optical coherence tomography were measured every month for 6 months. RESULTS:
      Thirty-eight patients were enrolled and randomized to IVB group (n = 19) and IVB
      + TRP group (n = 19). Both groups showed similar thinning in CRT at 1 week after
      IVB, IVB + TRP group maintained thinner retina at 2 (p = 0.0072) and 3 (p =
      0.0086) months compared with IVB group in whom turned to thickened almost back to
      baseline at 3 months. The number of reinjections in IVB group (1.58 +/- 0.69) was
      significantly greater (p = 0.0025) than that in IVB + TRP group (0.83 +/- 0.62).
      BCVA significantly improved at 6 month in IVB + TRP group (p = 0.015), but not in
      IVB group. CONCLUSION: TRP of NPAs reduced the amount of ME recurrence following
      IVB compared to IVB alone.

PMID- 25989710
TI  - The zoonotic potential of Mycobacterium avium ssp. paratuberculosis: a systematic
      review and meta-analyses of the evidence.
AB  - This systematic review-meta-analysis appraises and summarizes all the available
      research (128 papers) on the zoonotic potential of Mycobacterium avium ssp.
      paratuberculosis. The latter has been debated for a century due to pathogenic and
      clinical similarities between Johne's disease in ruminants and Crohn's disease
      (108 studies) in humans and recently for involvement in other human diseases;
      human immunodeficiency virus (HIV) infection (2), sarcoidosis (3), diabetes
      mellitus type 1 (T1DM) (7) and type 2 (3), multiple sclerosis (5) and Hashimoto's
      thyroiditis (2). Meta-analytical results indicated a significant positive
      association, consistently across different laboratory methods for Crohn's disease
      [odds ratio (OR) range 4.26-8.44], T1DM (OR range 2.91-9.95) and multiple
      sclerosis (OR range 6.5-7.99). The latter two and the thyroiditis hypothesis
      require further investigation to confirm the association. Meta-regression of
      Crohn's disease studies using DNA detection methods indicated that choice of
      primers and sampling frame (e.g. general population vs. hospital-based sample)
      explained a significant proportion of heterogeneity. Other epidemiological
      studies demonstrated a lack of association between high-risk occupations and
      development of Crohn's disease. Due to knowledge gaps in understanding the role
      of M. paratuberculosis in the development or progression of human disease, the
      evidence at present is not strong enough to inform the potential public health
      impact of M. paratuberculosis exposure. 

PMID- 25989709
TI  - Birthweight and Childhood Cancer: Preliminary Findings from the International
      Childhood Cancer Cohort Consortium (I4C).
AB  - BACKGROUND: Evidence relating childhood cancer to high birthweight is derived
      primarily from registry and case-control studies. We aimed to investigate this
      association, exploring the potential modifying roles of age at diagnosis and
      maternal anthropometrics, using prospectively collected data from the
      International Childhood Cancer Cohort Consortium. METHODS: We pooled data on
      infant and parental characteristics and cancer incidence from six geographically
      and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and
      Children (UK), the Collaborative Perinatal Project (USA), the Danish National
      Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian
      Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey
      (Australia)]. Birthweight metrics included a continuous measure, deciles, and
      categories (>= 4.0 vs. < 4.0 kilogram). Childhood cancer (377 cases diagnosed
      prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute
      lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated
      hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional
      hazards models stratified by cohort. RESULTS: A linear relationship was noted for
      each kilogram increment in birthweight adjusted for gender and gestational age
      for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for
      leukaemia. There were no significant interactions with maternal pre-pregnancy
      overweight or pregnancy weight gain. Birthweight >= 4.0 kg was associated with
      non-leukaemia cancer among children diagnosed at age >= 3 years [HR = 1.62; 95%
      CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for
      difference = 0.02]. CONCLUSION: Childhood cancer incidence rises with increasing
      birthweight. In older children, cancers other than leukaemia are particularly
      related to high birthweight. Maternal adiposity, currently widespread, was not
      demonstrated to substantially modify these associations. Common factors
      underlying foetal growth and carcinogenesis need to be further explored.

PMID- 25989711
TI  - Association of IRF8 gene polymorphisms with autoimmune thyroid disease.
AB  - BACKGROUND: The occurrence of autoimmune thyroid disease (AITD) is known to have
      a major adverse effect on interferon (INF)-alpha treatment. The genetic variant
      of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with
      susceptibility to systemic lupus erythematosus and multiple sclerosis. In this
      study, we investigated possible associations of the IRF8 polymorphisms,
      rs17445836 and rs2280381, with AITD in an ethnic Chinese population. MATERIAL AND
      METHODS: In total, 278 patients with Graves' disease (GD) and 55 patients with
      Hashimoto's thyroiditis (HT), and 252 healthy controls were enrolled. Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct
      sequencing were used for genotyping. RESULTS: Significantly lower frequencies of
      the GA genotype and A allele of rs17445836 were found in the HT group than in the
      control group (P = 0.028, odds ratio (OR) = 4.71 and P = 0.022, OR = 4.40,
      respectively). Both rs17445836 and rs2280381 were associated with the presence of
      an antimicrosomal antibody (AmiA), and rs2280381 was also associated with the
      presence of an antithyroglobulin antibody (ATA) in AITD. Moreover, rs17445836 was
      associated with the level of AmiA in AITD. CONCLUSIONS: rs17445836 of IRF8 is a
      possible genetic variant associated with the development of HT. rs17445836 was
      associated with the production of thyroid antibody, and the GG genotype of
      rs17445836 was associated with a higher AmiA titre than the GA genotype.

PMID- 25989712
TI  - Characterization of Red/Green Cyanobacteriochrome NpR6012g4 by Solution Nuclear
      Magnetic Resonance Spectroscopy: A Hydrophobic Pocket for the C15-E,anti
      Chromophore in the Photoproduct.
AB  - Cyanobacteriochromes (CBCRs) are cyanobacterial photosensory proteins distantly
      related to phytochromes. Like phytochromes, CBCRs reversibly photoconvert between
      a dark-stable state and a photoproduct via photoisomerization of the 15,16-double
      bond of their linear tetrapyrrole (bilin) chromophores. CBCRs provide
      cyanobacteria with complete coverage of the visible spectrum and near-ultraviolet
      region. One CBCR subfamily, the canonical red/green CBCRs typified by AnPixJg2
      and NpR6012g4, can function as sensors of light color or intensity because of
      their great variation in photoproduct stability. The mechanistic basis for
      detection of green light by the photoproduct state in this subfamily has proven
      to be a challenging research topic, with competing hydration and trapped-twist
      models proposed. Here, we use 13C-edited and 15N-edited 1H-1H NOESY solution
      nuclear magnetic resonance spectroscopy to probe changes in chromophore
      configuration and protein-chromophore interactions in the NpR6012g4 photocycle.
      Our results confirm a C15-Z,anti configuration for the red-absorbing dark state
      and reveal a C15-E,anti configuration for the green-absorbing photoproduct. The
      photoactive chromophore D-ring is located in a hydrophobic environment in the
      photoproduct, surrounded by both aliphatic and aromatic residues.
      Characterization of variant proteins demonstrates that no aliphatic residue is
      essential for photoproduct tuning. Taken together, our results support the
      trapped-twist model over the hydration model for the red/green photocycle of
      NpR6012g4.

PMID- 25989713
TI  - Is the current standard of care leading to cost-effective outcomes for patients
      with type 2 diabetes requiring insulin? A long-term health economic analysis for
      the UK.
AB  - AIMS: The aim of the analysis was to investigate whether insulin intensification,
      based on the use of intensive insulin regimens as recommended by the current
      standard of care in routine clinical practice, would be cost-effective for
      patients with type 2 diabetes in the UK. METHODS: Clinical data were derived from
      a retrospective analysis of 3185 patients with type 2 diabetes on basal insulin
      in The Health Improvement Network (THIN) general practice database. In total, 48%
      (614 patients) intensified insulin therapy, defined by adding bolus or premix
      insulin to a basal regimen, which was associated with a reduction in HbA1c and an
      increase in body mass index. Projections of clinical outcomes and costs (2011
      GBP) over patients' lifetimes were made using a recently validated type 2
      diabetes model. RESULTS: Immediate insulin intensification was associated with
      improvements in life expectancy, quality-adjusted life expectancy and time to
      onset of complications versus no intensification or delaying intensification by
      2, 4, 6, or 8 years. Direct costs were higher with the insulin intensification
      strategy (due to the acquisition costs of insulin). Incremental cost
      effectiveness ratios for insulin intensification were GBP 32,560, GBP 35,187, GBP
      40,006, GBP 48,187 and GBP 55,431 per QALY gained versus delaying intensification
      2, 4, 6 and 8 years, and no intensification, respectively. CONCLUSIONS: Although
      associated with improved clinical outcomes, insulin intensification as practiced
      in the UK has a relatively high cost per QALY and may not lead to cost-effective
      outcomes for patients with type 2 diabetes as currently defined by UK cost
      effectiveness thresholds.

PMID- 25989714
TI  - The clinico-pathological conference, based upon Giovanni Battista Morgagni's
      legacy, remains of fundamental importance even in the era of the vanishing
      autopsy.
AB  - Walter Cannon and Richard Cabot inaugurated the clinico-pathological conference
      (CPC) at Harvard Medical School at the beginning of the twentieth century, but
      this approach to anatomo-clinical correlation was first introduced by Giovanni
      Battista Morgagni at the University of Padua in the eighteenth century. The CPC
      consists of the presentation of a clinical case, in which past and recent medical
      histories of the patient, with all relevant information about laboratory tests
      including biopsy results, therapy and, eventually in a fatal case, the autopsy,
      are discussed. This is done for an audience of trainees and all physicians
      involved in the care for the patient. The CPC is still in use in many academic
      hospitals, as a teaching tool not only for undergraduate and graduate medical
      trainees, but also for postgraduate continuous medical education, in spite of the
      progressively declining autopsy rate. CPCs represent the ideal occasion for
      fruitful discussion between the two "souls" of medicine, i.e., the clinical, with
      its focus on the patient, and the pathological, with its focus on understanding
      disease. To discontinue using them would be equal to denying that modern medicine
      originated in Morgagni's method. 

PMID- 25989716
TI  - Neonatal testosterone exposure induces early development of follicular cysts
      followed by sympathetic ovarian hyperinnervation.
AB  - This study analysed the temporal association between ovarian cyst development
      induced by neonatal androgenisation and sympathetic innervation. Neonatal rats
      (postnatal Days 1 to 5) were treated with testosterone or dihydrotestosterone and
      the effects were evaluated at postnatal Days 20, 40, 90 or 180. Ovulation rate,
      number of cystic follicles and density of sympathetic fibres were analysed. The
      effects of surgical denervation or gonadotrophin stimulation were also assessed.
      Rats exposed to testosterone showed no oestrous cycle activity and did not
      ovulate, maintaining a polycystic ovarian morphology at all ages studied. Also, a
      significant increase in ovarian density of noradrenergic fibres was detected at
      postnatal Days 90 and 180. Sympathectomy was unable to re-establish ovarian
      activity; however, human chorionic gonadotrophin stimulation was enough to induce
      ovulation. The impact of dihydrotestosterone on ovarian function was less
      noticeable, showing the coexistence of corpora lutea and cystic structures
      without changes in sympathetic innervation. Our findings suggest that a
      remodelling of ovarian sympathetic innervation occurs as a response to
      modifications in the pattern of follicular growth induced by testosterone. A role
      of sympathetic innervation in the maintenance of the polycystic condition is
      suggested.

PMID- 25989715
TI  - Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the
      clinical, morphological, immunohistochemical, and molecular characteristics of an
      unusual pancreatic carcinoma.
AB  - We report a case of tumour in the head of the pancreas observed in a 57-year-old
      man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP)
      serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the
      tumour was predominantly composed of solid sheets of large eosinophilic cells
      with a prominent lymphoid infiltration without association neither with DNA
      microsatellite instability nor Epstein-Barr virus infection. The tumour was
      diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and
      glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic
      staining for AFP was focally observed. Moreover, tumour cells showed countless
      cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A
      primary hepatocellular carcinoma of the liver was ruled out by careful clinical
      analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here,
      we describe the first case of such variant associated with lymphoid stroma. The
      characteristic histologic features and the immunophenotypic profile help in
      distinguishing this carcinoma from other pancreatic tumours, notably from
      medullary carcinoma. 

PMID- 25989717
TI  - Comparison of Cutting Balloon Angioplasty and Percutaneous Balloon Angioplasty of
      Arteriovenous Fistula Stenosis: A Meta-Analysis and Systematic Review of
      Randomized Clinical Trials.
AB  - BACKGROUND: Hemodialysis (HD) access failure is a common cause of increased
      morbidity and healthcare cost in patients with end stage renal disease (ESRD).
      Percutaneous balloon angioplasty has been used to treat hemodialysis access
      stenosis but is complicated by a high rate of restenosis. Percutaneous cutting
      balloon (PCB) angioplasty is an alternative approach that has shown to reduce
      restenosis. OBJECTIVES: The aim of the study is to assess the safety and efficacy
      of PCB angioplasty in comparison with conventional and high-pressure balloon
      angioplasty in the treatment of hemodialysis access site stenosis. METHODS: We
      searched PubMed, EMBASE and the Cochrane Central register of controlled trials
      (CENTRAL) databases through August 2014 and selected studies using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We
      included all randomized clinical trials with a head-to-head comparison between
      PCB and conventional or high-pressure balloon angioplasty RESULTS: Three studies
      with 1034 participants (age 60.7 (+/-12.9) years and 50.1% males) with 525 in PCB
      and 509 in control arm were included in the analysis. The immediate procedural
      success rate was not significantly different in the PCB angioplasty and control
      arm respectively, (87.2% vs. 83.7% RD -0.02; 95%CI -0.06 to 0.01; P = 0.38). The
      six-month target lesion patency was significantly higher in the PCB angioplasty
      arm (67.2% vs. 55.6% RD 0.12; 95%CI 0.05-0.19; P < 0.05) with number needed to
      treat (NNT) of 9. The device related complications were not statistically
      significant between groups (RD 0.03; 95%CI -0.02 to 0.07; P = 0.26). CONCLUSIONS:
      PCB angioplasty is effective in treatment of hemodialysis access stenosis, with
      significantly higher six-month patency compared to balloon angioplasty.

PMID- 25989718
TI  - Diversity of Cervicovaginal Cytokine Response to Incident Chlamydia trachomatis
      Infection Among a Prospective Cohort of Young Women.
AB  - PROBLEM: Animal, in vitro, and ex vivo studies have identified several cytokines
      involved in host immunity to genital Chlamydia trachomatis (CT) infection.
      However, in vivo cytokine responses are not well described. Our objectives were
      to document cervicovaginal cytokine levels and intrawoman cytokine changes during
      incident CT in a prospective cohort. METHODS: From our prospective cohort, 62
      women had incident CT, comprising a CT-negative visit followed by a CT-positive
      visit. At these visits, cytokine protein levels (IL-6, IL-8, IL-1alpha, IL-1beta,
      MIP-1alpha, RANTES, IFN-gamma) were measured using cervicovaginal lavages and the
      MILLIPLEX(TM) /Luminex((r)) multiplex assay. Quartiles were defined for each
      cytokine from all 124 visits. RESULTS: At the group level, RANTES was higher (P <
      0.01) at the CT-positive visit than at baseline, but the other cytokines did not
      significantly differ. For intrawoman cytokine changes, women with a cytokine
      level that increased at least one quartile higher (going from baseline to the CT
      positive visit) ranged between 26 and 53%. Women with a cytokine level staying in
      the same quartile ranged between 32 and 48%. Women with a cytokine level that
      decreased at least one quartile lower ranged between 15 and 37%. CONCLUSION:
      Intrawoman cervicovaginal cytokine changes during incident CT appear
      heterogeneous and may reflect differences in natural host immunity.

PMID- 25989720
TI  - Angiodysplasia: new look at an old conundrum.
AB  - Angiodysplasia is a unifying concept and designation for all developmental
      vascular anomalies currently known in the medical literature as angiomatosis,
      arteriovenous malformation, congenital arteriovenous fistula, congenital
      hemangioma or lymphangiomatosis, telangiectasia, vascular hamartoma, and all
      those clinical disorders identified by eponyms, such as Klippel-Tranaunay
      syndrome and Rendu-Osler-Weber syndrome. A new classification is proposed to
      catalog the histomorphologic spectrum of angiodysplasia likely to be found in
      each individual case with the caveat that virtually all angiodysplastic lesions
      will have mixed histomorphology although one type may predominate. Examples of
      the most commonly encountered angiodysplastic lesions are described and
      illustrated in this review. 

PMID- 25989719
TI  - Health effects of cow's milk consumption in infants up to 3 years of age: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To summarize the best available evidence regarding the short- and long
      term health effects of cow's milk intake in healthy, full-term infants up to 3
      years of age. DESIGN: We conducted a systematic review and meta-analysis.
      SETTING: We searched MEDLINE (via PubMed), EMBASE and the Cochrane Library
      between 1960 and July 2013 and manually reviewed reference lists of pertinent
      articles. Two researchers independently reviewed abstracts and full-text articles
      and extracted relevant data. SUBJECTS: We included (randomized/non-randomized)
      controlled trials and observational studies. RESULTS: We included data from
      twenty-three studies (one randomized controlled trial, four non-randomized
      controlled trials, eight case-control studies and ten cohort studies) for the
      evidence synthesis. Pooled results of four studies revealed a higher risk of Fe
      deficiency anaemia for infants consuming cow's milk compared with those consuming
      follow-on formula (relative risk=3.76; 95 % CI 2.73, 5.19). For type 1 diabetes
      mellitus, six out of seven case-control studies did not show a difference in the
      risk of developing this disease based on the age of introduction of cow's milk.
      We did not find negative associations for other health effects. CONCLUSIONS:
      Cow's milk consumption in infancy is associated with an increased risk of
      developing Fe-deficiency anaemia. Limiting cow's milk consumption may be
      important to ensure an adequate Fe intake for infants and toddlers. High-quality
      patient information for caregivers is needed on how infants' Fe requirements can
      be met.

PMID- 25989721
TI  - Expression of metalloproteases by cardiac myocytes and fibroblasts in vitro.
AB  - Regulation of the turnover of extracellular matrix (ECM) components has been
      attributed in part to matrix metalloproteases (MMP). Isolated cardiac myocytes
      and fibroblasts from different developmental stages express different patterns of
      MMPs in vitro. Zymography of media and cell extracts of fibroblasts and myocytes
      indicated several apparent molecular weights (Mr) with gelatinolytic activity
      with prominent bands at 92 and 72 kDa. No caseinolytic activity was detected.
      These MMPs were characteristic of known MMP-2 and MMP-9. Fibroblasts
      predominantly expressed the latent 72-kDa MMP, whereas myocytes expressed a
      latent 92-kDa MMP. Expression of these MMPs was not affected by density of
      culture or the type of ECM substrate on which the cells were grown. Sodium
      dodecyl sulfate (SDS)-activated MMP-2 showed specific cleavage patterns on
      collagen types I and III but not on fibronectin, collagen type IV, or laminin.
      The reaction of SDS-activated MMP-2 produced a 140-kDa fragment from collagen
      types I and III. No specific substrate patterns were observed with activated MMP
      9. MMP-2 from fibroblasts could also be activated by mechanical tension developed
      by fibroblasts within collagen gels or by cyclically stretching Silastic
      membranes on which the fibroblasts were grown. When mechanical tension was
      inhibited in collagen gels by antibodies against the beta1 integrin, the 72-kDa
      MMP, or cytochalasin D, the activated band at 62 kDa was not detected.
      Immunocytochemical localization with antibodies against MMP-2 showed a weak
      reaction on cardiac myocytes, but intense staining around the focal adhesions of
      migrating fibroblasts. In collagen gels, staining was localized to the leading
      pseudopodia of the fibroblasts. Together, these data indicate that the rat MMP-2
      is a collagenase primarily associated with cardiac fibroblasts, activated by
      mechanical tension, and may be important in cellular ECM interactions. 

PMID- 25989722
TI  - Differences in the distribution of versican, decorin, and biglycan in
      atherosclerotic human coronary arteries.
AB  - The distributions of versican, biglycan, and decorin have been examined in
      segments of normal and atherosclerotic human coronary arteries using antibodies
      directed against the core proteins of these macromolecules. Versican
      immunostaining was prominent throughout the extracellular matrix (ECM) in regions
      of the vessels that contained abundant smooth-muscle cells, such as in diffuse
      intimal thickenings, fibrous caps, and in zones of loose, myxoid connective
      tissue. Versican also was present in smooth-muscle-rich thrombi and at borders of
      the lipid-rich cores of advanced atherosclerotic lesions. Biglycan immunostaining
      was observed in diffuse intimal thickenings, fibrous caps, and myxoid areas, but,
      unlike versican, it was abundant in the lipid-rich core of advanced plaques.
      However, biglycan immunostaining was absent in smooth-muscle cell-enriched
      thrombi. Decorin immunostaining paralleled biglycan immunostaining except that it
      was conspicuously absent in the myxoid areas of the plaque and markedly reduced
      in diffuse intimal thickenings. Both biglycan and decorin immunostaining were
      consistently associated with some of the microvessels in the thrombi and in
      advanced atherosclerotic plaques. Taken together, these results indicate that
      specific proteoglycans distribute to topographically defined regions of normal
      and atherosclerotic human coronary arteries and that these different
      distributions may indicate a diversity of functions in normal and pathologic
      processes of the arterial wall. 

PMID- 25989723
TI  - Cardiac valve prostheses at autopsy: an analysis of 337 cases with
      clinicopathologic correlation.
AB  - We evaluated the pathologic findings at autopsy in 337 patients who had undergone
      cardiac valve replacement over 10 years (1982 to 1991). Rheumatic heart disease
      was the most common indication for valve replacement (84% of cases). Among the
      255 patients with short-term survival (<1 month), in 162 cases (63.5%), the cause
      of death was related to surgery and/or underlying cardiovascular conditions. Host
      prosthetic valve interactions contributed to mortality in 14.9% cases. However,
      in longtime survivors (82 patients), a significant number (86.5%) showed evidence
      of prosthesis-related complications, such as infective endocarditis, thrombosis,
      anticoagulant-related hemorrhage, and bioprosthetic valve degeneration. 

PMID- 25989724
TI  - Food restriction protects and obesity increases vulnerability to isoproterenol
      induced myocardial necrosis in rats.
AB  - Factors that determine the wide variation in the severity of isoproterenol
      induced myocardial necrosis (ISO-MN) are numerous and poorly defined. We have
      investigated the role of age, body weight, food intake, and genetic strain
      differences on vulnerability to ISO-MN in rats. The proportion of apical
      myocardium that became necrotic after administration of toxic doses of
      isoproterenol was used as the index of ISO-MN. Sprague-Dawley (SD) rats of 8 to
      10 and 16 to 18 weeks of age had 3.4 and 3.3 fold more severe apical myocardial
      lesions respectively than 5- to 6-week-old rats. Among Zucker rats of 8 to 9
      weeks of age there was 5.2 times more necrosis in obese than in lean animals.
      Fifty percent food restriction for one week, or 24 hours of fasting in 8- to 10
      week-old SD rats led to a 50% reduction in the area of necrosis compared to ad
      lib fed controls. Under similar conditions 16- to 18-week-old rats showed a
      similar reduction with 24-hour fasting, but 50% food restriction had no effect.
      Similarly, food restriction had no effect in 5- to 6-week-old SD or obese Zucker
      rats. Feeding of diets containing lard, or olive, corn, or fish oils for one week
      had no significant effect on ISO-MN in SD rats. These results suggests that age,
      obesity, and food intake alter vulnerability to ISO-MN. 

PMID- 25989725
TI  - The placental mTOR-pathway: correlation with early growth trajectories following
      intrauterine growth restriction?
AB  - Idiopathic intrauterine growth restriction (IUGR) is a result of impaired
      placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up
      growth are of higher risk for cardiovascular and metabolic co-morbidities in
      adult life. Mammalian target of rapamycin (mTOR) was recently shown to function
      as a placental nutrient sensor. Thus, we determined possible correlations of
      members of the placental mTOR signaling cascade with auxologic parameters of
      postnatal growth. The protein expression and activity of mTOR-pathway signaling
      components, Akt, AMP-activated protein kinase alpha, mTOR, p70S6kinase1 and
      insulin receptor substrate-1 were analysed via western blotting in IUGR v.
      matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was
      immunohistochemically stained in placental sections. Data from western blot
      analyses were correlated with retrospective auxological follow-up data at 1 year
      of age. We found significant catch-up growth in the 1st year of life in the IUGR
      group. MTOR and its activated form are immunohistochemically detected in multiple
      placental compartments. We identified correlations of placental mTOR-pathway
      signaling components to auxological data at birth and at 1 year of life in IUGR.
      Analysis of the protein expression and phosphorylation level of mTOR-pathway
      components in IUGR and AGA placentas postpartum, however, did not reveal
      pathognomonic changes. Our findings suggest that the level of activated mTOR
      correlates with early catch-up growth following IUGR. However, the complexity of
      signals converging at the mTOR nexus and its cellular distribution pattern seem
      to limit its potential as biomarker in this setting. 

PMID- 25989726
TI  - Rail or roll: a new, convenient and safe way to position self-gripping meshes in
      open inguinal hernia repair.
AB  - PURPOSE: In open inguinal hernia repair self-gripping meshes are currently
      commonly employed. Assumed benefits are saving of time, ease of handling and
      omission of fixation. Self-gripping meshes are, however, not as easy to handle
      and position as commonly stated. We describe a newly developed way of intra
      operative mesh preparation and implantation and compare it to the conventional
      technique of insertion of self-gripping meshes. METHODS: A two-armed, randomized
      trial with 64 patients was performed. For implantation of the self-gripping,
      light weight and partially absorbable mesh we used either a newly described
      rolling technique (group 1: n = 32) or the conventional way of insertion (group
      2: n = 32). Primary endpoints of the study were feasibility with regard to actual
      implantation time and surgeons' satisfaction with the methods. Secondary
      endpoints were total operating time, length of hospital stay, postoperative pain,
      duration of pain medication intake and postoperative morbidity. In addition all
      patients were prospectively followed up according to the Hernia Med(r) registry's
      standards. RESULTS: Implantation time (seconds) 140 +/- 74 vs. 187 +/- 84, p =
      0.008, duration of pain medication intake (days) 3.6 +/- 2.8 vs. 4.8 +/- 2.6; p =
      0.046 and postoperative morbidity 2 (6%) vs. 8 (25%) was significantly beneficial
      in group 1 (rolling technique) compared to group 2 (conventional method). Blinded
      questionnaire revealed that rolling the mesh is generally easier with less
      repositioning maneuvers than conventional placement. Neither overall procedure
      time, length of stay nor postoperative pain scores differed significantly between
      groups. CONCLUSION: The newly introduced rolling technique for the actual
      placement of self-gripping meshes in open inguinal hernia repair is technically
      less demanding and therefore significantly faster when compared to the
      conventional way of insertion of the same product. In addition the rolling
      technique has shown to be safe for the patients and to also provide higher
      surgeons' satisfaction.

PMID- 25989727
TI  - Deactivation of signal amplification by reversible exchange catalysis, progress
      towards in vivo application.
AB  - The catalyst which is used in the signal amplification by reversible exchange
      (SABRE) process facilitates substrate hyperpolarisation while acting to speed up
      the rate of relaxation. Consequently, the lifetime over which the hyperpolarised
      contrast agent is visible is drastically reduced. We show that the addition of a
      chelating ligand, such as bipyridine, rapidly deactivates the SABRE catalyst
      thereby lengthening the agent's relaxation times and improving the potential of
      SABRE for diagnostic MRI. 

PMID- 25989729
TI  - Erratum: Whole-genome sequence-based analysis of thyroid function.

PMID- 25989728
TI  - Treatment of Sarcoidosis.
AB  - In general, sarcoidosis treatment should be offered to palliate symptoms and
      improve quality of life or to prevent end-organ disease. Symptoms include
      pulmonary as well as extra-pulmonary manifestations of the disease. The
      assessment of response to disease includes functional studies such as the forced
      vital capacity. Radiologic imaging such as chest x-ray has also been used to
      assess response, although standardized measures have rarely been tested. There
      are sufficient clinical trials to make specific recommendations regarding
      treatment of symptomatic pulmonary disease. Initial therapy is usually prednisone
      or a similar glucocorticoid. However, there are several features of this
      treatment which are unknown. This includes the initial dose, timing of reduction
      of dose, and when to discontinue treatment. Since many patients are intolerant of
      prednisone, steroid-sparing alternatives have been studied. Methotrexate is the
      most widely used anti-metabolite, but azathioprine, leflunomide, and
      mycophenolate have also been reported as helpful. The biologic agents, especially
      monoclonal anti-tumor necrosis factor (anti-TNF) antibodies, have proved
      effective in patients who have failed other treatments. Infliximab, the most
      widely studied anti-TNF antibody, has proved effective for a range of refractory
      sarcoidosis. However, there remain questions regarding dose and duration of
      therapy. For the clinician, the many treatment options allow for a specific
      treatment regimen for each patient which minimizes risk while enhancing benefit. 

PMID- 25989730
TI  - Apparent left ventricular cavity dilatation during PET/CT in hypertrophic
      cardiomyopathy: Clinical predictors and potential mechanisms.
AB  - BACKGROUND: Apparent left ventricular cavity dilatation (LVCD) in patients with
      hypertrophic cardiomyopathy (HCM) is an incompletely understood phenomenon. We
      aimed at investigating its clinical predictors and potential mechanisms. METHODS:
      Sixty one HCM patients underwent N-13-ammonia PET for visual evaluation of LVCD,
      transient ischemic dilatation (TID) index, myocardial blood flow (MBF), coronary
      flow reserve (CFR), and regional myocardial perfusion (rMP). TID index was also
      derived at 2-4 and 15-20 minutes. RESULTS: Visual LVCD and quantitative TID
      (>1.13 abnormal) agreement were excellent (k 0.91; P < .0001). LVCD-positive (n =
      32) patients had greater LV thickness (2.26 +/- 0.59 vs 1.92 +/- 0.41 cm; P =
      .005), but lower stress MBF (1.66 +/- 0.42 vs 2.07 +/- 0.46 mL/minute/g; P <
      .0001), and CFR (1.90 +/- 0.46 vs 2.46 +/- 0.69; P < .0001) than LVCD-negative (n
      = 29) patients. Abnormal rMP was present in 31/32 LVCD-positive but only 12/29 (P
      < .0001) LVCD-negative. TID index was higher at 2-4 (1.30 +/- 0.13) than at 15-20
      minutes (1.27 +/- 0.12; P = .001) in LVCD-positive, whereas it was the same (1.04
      +/- 0.07 vs 1.04 +/- 0.07; P = .9) in LVCD-negative. In multivariate analysis,
      global peak MBF, abnormal rMP, and LV thickness were the best predictors of LVCD.
      CONCLUSION: Apparent LVCD is a common finding in HCM, intimately related to
      abnormal myocardial perfusion, globally impaired vasodilator flow reserve, and
      degree of hypertrophy. In addition to regional and/or diffuse subendocardial
      ischemia, some degree of true LV chamber dilatation may also contribute to the
      occurrence of apparent LVCD in HCM.

PMID- 25989731
TI  - Complete and incomplete revascularization: Whose definition is it anyway?

PMID- 25989732
TI  - Efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin cream
      in chinese patients with melasma: a randomized, double-blind, placebo-controlled,
      multicenter, parallel-group study.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to determine the efficacy and safety
      of fluocinolone acetonide, hydroquinone, and tretinoin (FAHT) cream for the
      treatment of moderate and severe facial melasma. The primary objective was
      assessment of clinical efficacy, instrumental measured efficacy, and integral
      therapeutic efficacy at the end of weeks 4 and 8. METHODS: A total of 233
      subjects were randomly allocated (1:1 ratio) to receive topically administered
      FAHT cream (n = 117) or placebo (n = 116) once nightly for 8 weeks. Observed side
      effects were documented throughout. RESULTS: In the per protocol set (PPS; those
      subjects who met all requirements of the protocol), the integral therapeutic
      efficacy rate of FAHT cream on moderate and severe melasma was 68.57% (vs.
      placebo, 0.94%), the clinical effective rate of FAHT cream was 74.29 % (vs.
      placebo, 0.94%), and the instrumental measure efficacy of FAHT cream was 71.43%
      (vs. placebo, 6.60%). The difference in efficacy between the two groups was
      statistically significant (p < 0.001). In the full analysis set (FAS; the PPS and
      those subjects who were lost to follow-up but received at least one study
      treatment), the integral therapeutic efficacy rate of FAHT cream was 64.60% (vs.
      placebo, 0.88%), the clinical effective rate of FAHT cream was 69.91% (vs.
      placebo, 0.88%), and the instrumental measure efficacy of FAHT cream was 69.03 %
      (vs. placebo, 7.08%). The difference in efficacy between the two groups was
      statistically significant (p < 0.001). Of 113 subjects in the FAHT group, 34
      (30.1%) reported adverse effects. Most of the pathological adverse effects were
      mild and resolved with either continuous treatment or discontinuation. Of 113
      subjects in the placebo group, three (2.6%) reported mild adverse effects. No
      severe adverse effects or other abnormal clinical results were associated with
      the study treatment. CONCLUSION: FAHT cream is efficacious, well tolerated, and
      has a high margin of safety for the treatment of moderate and severe melasma in
      the Chinese population.

PMID- 25989733
TI  - Diclofenac sodium injection (akis((r)), dicloin ((r))): a review of its use in
      the management of pain.
AB  - A novel formulation of diclofenac sodium suitable for subcutaneous or
      intramuscular injection (Akis((r)), Dicloin((r))) has been developed using the
      complexing agent hydroxypropyl-beta-cyclodextrin (HPbetaCD) as a solubility
      enhancer. Diclofenac HPbetaCD is available in several European countries, where
      it is indicated for use in adults with acute forms of pain, including
      postoperative pain. Clinical trials have demonstrated the analgesic efficacy of
      diclofenac HPbetaCD in terms of relieving moderate to severe postoperative pain
      in patients undergoing dental surgery or minor orthopaedic surgery. Subcutaneous
      diclofenac HPbetaCD also effectively relieved moderate to severe neuropathic
      pain, related to cancer or not. Diclofenac HPbetaCD was generally well tolerated
      in clinical trials, with injection-site reactions among the most commonly
      reported adverse events. The local tolerability of diclofenac HPbetaCD was
      consistently rated as 'good' or 'excellent' across all studies. Subcutaneous
      administration of diclofenac is a valid alternative to intramuscular delivery,
      with the advantages of easier administration, the availability of additional body
      sites suitable for injection and the potential for self-administration. Thus,
      diclofenac HPbetaCD 25, 50 or 75 mg/mL solution for subcutaneous or intramuscular
      injection extends the treatment options available for use in the management of
      pain in adults. 

PMID- 25989734
TI  - A promising RVO4:Eu(3+), Li(+)@SiO2 (R = Gd, Y and Gd/Y) red-emitting phosphor
      with improved luminescence (cd/m(2)) and colour purity for optical display
      applications.
AB  - Red emission intensity was optimized in three stages, by investigating the
      effects of: (i) host composition (Gd, Y and Gd/Y), (ii) codoping Li(+) as a
      sensitizer and, finally, (iii) with a SiO2 shell coating as a protecting layer.
      Lanthanide vanadate powder phosphors were synthesized using a modified colloidal
      precipitation technique. The effects of SiO2 coating on phosphor particles were
      characterized using scanning electron microscopy (SEM)-EDAX, transmission
      electron microscopy (TEM), Fourier transform infrared (FTIR) and
      photoluminescence (PL) measurements. An improvement in the PL intensity on Li
      codoping was due to improved crystallinity, which led to higher oscillating
      strengths for the optical transitions, and also a lowering of the inversion
      symmetry of Eu(3+) ions. Red emission intensity due to (5)D0  -> (5)D2 transition
      of the phosphor Y0.94VO4:Eu(3+)0.05, Li(+)0.01 was enhanced by 22.28% compared
      with Y0.95VO4:Eu(3+)0.05, and was further improved by 58.73% with SiO2 coating.
      The luminescence intensity (I) and colour coordinates (x, y) of the optimized
      phosphor Y0.94VO4:Eu(3+)0.05, Li(+)0.01@SiO2, where I = 13.07 cd/m(2) and (x =
      0.6721, y = 0.3240), were compared with values for a commercial red phosphor
      (Y2O2S:Eu(3+)), where I = 27 cd/m(2) and (x = 0.6522, y = 0.3437). The measured
      colour coordinates are superior to those of the commercial red phosphor, and
      moreover, match well with standard NTSC values (x = 0.67, y = 0.33).

PMID- 25989737
TI  - [Classification of gliomas. Current progress and perspectives].
AB  - The diagnostic subdivision of gliomas is traditionally based on histological
      features as defined by the World Health Organization (WHO) classification of
      tumors of the central nervous system. In recent years molecular studies have
      identified a number of genetic and epigenetic markers that could contribute to an
      improved tumor classification and better prediction of response to therapy and
      prognosis in the individual patient. The most important molecular tests with
      differential diagnostic relevance in patients with astrocytic and
      oligodendroglial tumors include the detection of genetic mutations in the
      isocitrate dehydrogenase 1 (IDH1), IDH2, alpha thalassemia/mental retardation
      syndrome X-linked (ATRX), histone H3.3 (H3F3A) and v-raf murine sarcoma viral
      oncogene homolog B (BRAF) genes as well as the demonstration of codeletions of
      chromosomal arms 1p and 19q. Important predictive markers that have been linked
      to the response to alkylating chemotherapy are O-6-methylguanine-DNA
      methyltransferase (MGMT) promoter methylation in glioblastoma patients and 1p/19q
      codel status in anaplastic glioma patients. Oncogenic c11orf95/RELA fusion gene
      formation is characteristic for a subgroup of patients with supratentorial
      ependymoma. In addition to diagnostic testing of individual genes, novel
      microarray and next generation sequencing (NGS) techniques show promising
      perspectives in glioma diagnostics. The assessment of DNA methylation profiles
      using DNA methylation arrays representing 450,000 CpG dinucleotides distributed
      throughout the human genome (450 k array test) now allows the robust molecular
      classification of gliomas into clinically relevant entities and variants.
      Moreover, glioma-associated gene panel NGS promises the timely parallel
      sequencing of relevant diagnostic and predictive marker genes in a single test.
      It will now be a major task to integrate these novel results and techniques into
      the conventional histological procedures in the up-coming revision of the WHO
      classification. 

PMID- 25989738
TI  - [Therapeutic options for brain metastases].
AB  - Brain metastases are common in cancer patients, especially in lung cancer, breast
      cancer and melanoma and represent a therapeutic challenge. Established local
      therapeutic procedures include neurosurgical resection, stereotactic irradiation
      and whole brain radiotherapy; however, for selected patients novel targeted
      therapies with documented activity against brain metastases are emerging. These
      include v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors, the
      anticytotoxic T lymphocyte-associated protein 4 (CTL4A) antibodies ipilimumab in
      melanoma, HER2 antagonists in breast cancer and epidermal growth factor receptor
      (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors in non-small cell lung
      cancer. Therefore, the modern management of patients with brain metastases should
      be performed in an interdisciplinary setting and under consideration of relevant
      molecular markers to facilitate optimal patient outcome. 

PMID- 25989735
TI  - Biological ageing and frailty markers in breast cancer patients.
AB  - Older cancer patients are a highly heterogeneous population in terms of global
      health and physiological reserves, and it is often difficult to determine the
      best treatment. Moreover, clinical tools currently used to assess global health
      require dedicated time and lack a standardized end score. Circulating markers of
      biological age and/or fitness could complement or partially substitute the
      existing screening tools. In this study we explored the relationship of potential
      ageing/frailty biomarkers with age and clinical frailty. On a population of 82
      young and 162 older non-metastatic breast cancer patients, we measured mean
      leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated
      upon activation, normal T cell expressed and secreted (RANTES), monocyte
      chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also
      developed a new tool to summarize clinical frailty, designated Leuven
      Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi
      continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL
      6 levels were associated with chronological age in both groups and with clinical
      frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1
      only correlated with age. Plasma IL-6 should be further explored as frailty
      biomarker in cancer patients. 

PMID- 25989739
TI  - Utility of T-wave alternans during night time as a predictor for ventricular
      fibrillation in patients with Brugada syndrome.
AB  - The prognostic value of T-wave alternans (TWA) during the night time in patients
      with Brugada syndrome (Br-S) remains unknown. We assessed TWA for risk
      stratification using 24-h multichannel Holter electrocardiogram (24-M-ECG) in Br
      S. We enrolled 129 patients with Br-S [grouped according to histories of
      ventricular fibrillation (VF), n = 16; syncope, n = 10; or no symptoms
      (asymptomatic), n = 103] and 11 controls. Precordial electrodes were attached to
      the third (3L-V1, 3L-V2) and fourth (4L-V1, 4L-V2 and 4L-V5) intercostal spaces.
      We measured the values of maximum TWA (max-TWA) during the night time (12 a.m.-6
      a.m.) and the day time (12 p.m.-6 p.m.) and calculated parameters of heart rate
      variability. Compared to the asymptomatic and control groups, the VF and syncope
      groups showed significantly greater 3L-V2 max-TWA during the night time. The
      cutoff value for the 3L-V2 max-TWA during the night time was determined as 20 uV
      (sensitivity 94 % and specificity 48 %; p = 0.01). Multivariate analysis revealed
      that 3L-V2 max-TWA during the night time >=20 uV and previous VF episodes were
      independent predictors of future VF episodes. During a mean follow-up period of
      68 +/- 37 months, 16 patients experienced VF episodes. The incidence of VF
      episodes was the highest during the night time (p < 0.001). The 3L-V2 max-TWA
      during the night time may be a useful predictor for VF episodes in patients with
      Br-S. 

PMID- 25989740
TI  - Disparities in the prenatal detection of critical congenital heart disease.
AB  - OBJECTIVES: Prenatal diagnosis of critical congenital heart disease, which
      requires surgical or catheter intervention in the first 30 days of life, allows
      for delivery at a specialized center and can reduce preoperative morbidity and
      mortality. We sought to identify the risk factors for a missed prenatal diagnosis
      of critical congenital heart disease. METHODS: Patients presenting to the
      Children's Hospital of Wisconsin with critical congenital heart disease from 2007
      to 2013 were included. Those with a prenatal diagnosis were compared with those
      with a postnatal diagnosis. RESULTS: The cohort included 535 patients with
      prenatal diagnosis made in 326 (61%). The prenatal diagnostic rate improved from
      44% in 2007 to 69% in 2013. Independent factors associated with a postnatal
      diagnosis were a lesion that required a view other than a four chamber view to
      make the diagnosis (p < 0.0001), absence of another organ system anomaly (p <
      0.0001), and living in a higher poverty (p = 0.02) or lower population density
      communities (p = 0.002). CONCLUSIONS: While the prenatal diagnostic rate for
      critical congenital heart disease is improving, those living in impoverished or
      rural communities are at highest risk of not having a diagnosis made prenatally.
      Interventions to improve prenatal detection of congenital heart disease should
      target these vulnerable areas.

PMID- 25989741
TI  - Predicting disease progression from short biomarker series using expert advice
      algorithm.
AB  - Well-trained clinicians may be able to provide diagnosis and prognosis from very
      short biomarker series using information and experience gained from previous
      patients. Although mathematical methods can potentially help clinicians to
      predict the progression of diseases, there is no method so far that estimates the
      patient state from very short time-series of a biomarker for making diagnosis
      and/or prognosis by employing the information of previous patients. Here, we
      propose a mathematical framework for integrating other patients' datasets to
      infer and predict the state of the disease in the current patient based on their
      short history. We extend a machine-learning framework of "prediction with expert
      advice" to deal with unstable dynamics. We construct this mathematical framework
      by combining expert advice with a mathematical model of prostate cancer. Our
      model predicted well the individual biomarker series of patients with prostate
      cancer that are used as clinical samples. 

PMID- 25989742
TI  - Age-dependent neuromuscular impairment in prion protein knockout mice.
AB  - INTRODUCTION: The cellular prion protein (PrP(C) ) is commonly recognized as the
      precursor of prions, the infectious agents of the fatal transmissible spongiform
      encephalopathies, or prion diseases. Despite extensive effort, the physiological
      role of PrP(C) is still ambiguous. Evidence has suggested that PrP(C) is involved
      in different cellular functions, including peripheral nerve integrity and
      skeletal muscle physiology. METHODS: We analyzed the age-dependent influence of
      PrP(C) on treadmill test-based aerobic exercise capacity and on a series of
      morphological and metabolic parameters using wild-type and genetically modified
      mice of different ages expressing, or knockout (KO) for, PrP(C) . RESULTS: We
      found that aged PrP-KO mice displayed a reduction in treadmill performance
      compared with PrP-expressing animals, which was associated with peripheral nerve
      demyelination and alterations of skeletal muscle fiber type. CONCLUSION: PrP-KO
      mice have an age-dependent impairment of aerobic performance as a consequence of
      specific peripheral nerve and muscle alterations.

PMID- 25989743
TI  - Erratum to: In vitro digestion of starches in a dynamic gastrointestinal model:
      an innovative study to optimize dietary management of patients with hepatic
      glycogen storage diseases.

PMID- 25989744
TI  - Cephalopod-Inspired Miniaturized Suction Cups for Smart Medical Skin.

PMID- 25989746
TI  - Three-dimensional dictionary-learning reconstruction of (23)Na MRI data.
AB  - PURPOSE: To reduce noise and artifacts in (23)Na MRI with a Compressed Sensing
      reconstruction and a learned dictionary as sparsifying transform. METHODS: A
      three-dimensional dictionary-learning compressed sensing reconstruction algorithm
      (3D-DLCS) for the reconstruction of undersampled 3D radial (23)Na data is
      presented. The dictionary used as the sparsifying transform is learned with a K
      singular-value-decomposition (K-SVD) algorithm. The reconstruction parameters are
      optimized on simulated data, and the quality of the reconstructions is assessed
      with peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). The
      performance of the algorithm is evaluated in phantom and in vivo (23)Na MRI data
      of seven volunteers and compared with nonuniform fast Fourier transform (NUFFT)
      and other Compressed Sensing reconstructions. RESULTS: The reconstructions of
      simulated data have maximal PSNR and SSIM for an undersampling factor (USF) of 10
      with numbers of averages equal to the USF. For 10-fold undersampling, the PSNR is
      increased by 5.1 dB compared with the NUFFT reconstruction, and the SSIM by 24%.
      These results are confirmed by phantom and in vivo (23)Na measurements in the
      volunteers that show markedly reduced noise and undersampling artifacts in the
      case of 3D-DLCS reconstructions. CONCLUSION: The 3D-DLCS algorithm enables
      precise reconstruction of undersampled (23)Na MRI data with markedly reduced
      noise and artifact levels compared with NUFFT reconstruction. Small structures
      are well preserved.

PMID- 25989747
TI  - Cardioprotective Effects of Tannic Acid on Isoproterenol-Induced Myocardial
      Injury in Rats: Further Insight into 'French Paradox'.
AB  - Tannic acid (TA) is a polyphenolic compound, which has shown diverse
      pharmacological effects with antimutagenic, anticarcinogenic and antibactericidal
      properties. However, cardioprotective effects of TA have not been reported. To
      investigate the protective effects of TA, rats were administered TA for 7 days
      and then intoxicated with isoproterenol (ISO). Myocardial ischemia injury was
      indicated by changes in electrocardiographic (ECG) patterns, morphology and
      cardiac marker enzymes. Furthermore, protein expression levels of c-fos, c-jun,
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), cleaved
      caspase-3 and -9 were analyzed by immunohistochemistry, and activities of
      apoptosis-related proteins Bax, Bcl-2, caspase-3 and nuclear factor kappa B (NF
      kappaB) were detected by Western blot. Pretreatment with TA ameliorated changes
      in morphology and ECG, reduced activities of marker enzymes, suppressed
      overexpression of apoptosis-related proteins, upregulated expression of
      antioxidants. Moreover, TA pretreatment contributed to the decrease in ratio of
      Bax/Bcl-2, as well as reduced expression of TNF-alpha, IL-1beta, caspase-3,
      cleaved-caspase-3 and -9. TA displayed cardioprotective effects, which may be
      attributed to lowering of Bax/Bcl-2 ratio, c-fos and c-jun expression and
      inhibition of NF-kappaB activation, as well as oxidative stress, inflammation and
      apoptosis. These findings provide further insight into the 'French paradox' and
      the mechanisms underlying the beneficial effects of TA. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 25989745
TI  - Dairy intake after prostate cancer diagnosis in relation to disease-specific and
      total mortality.
AB  - Information regarding postdiagnostic dairy intake and prostate cancer survival is
      limited. We evaluated intake of total, high-fat and low-fat dairy after prostate
      cancer diagnosis in relation to disease-specific and total mortality. We included
      926 men from the Physicians' Health Study diagnosed with non-metastatic prostate
      cancer between 1982 and 2000 who completed a diet questionnaire a median of 5
      years after diagnosis and were followed thereafter for a median of 10 years to
      assess mortality. Cox proportional hazards regression was used to estimate
      associations between dairy intake and prostate cancer specific and all-cause
      mortality. During 8,903 person-years of follow-up, 333 men died, 56 due to
      prostate cancer. Men consuming >=3 servings/day of total dairy products had a 76%
      higher risk of total mortality and a 141% higher risk of prostate cancer-specific
      mortality compared to men who consumed less than 1 dairy product/day (hazard
      ratio (HR) = 1.76, 95% confidence interval (CI): 1.21, 2.55, ptrend  < 0.001 for
      total mortality; HR = 2.41, 95% CI: 0.96, 6.02, ptrend  = 0.04 for prostate
      cancer-specific mortality). The association between high-fat dairy and mortality
      risk appeared to be stronger than that of low-fat dairy, but the difference
      between them was not statistically significant (p for difference = 0.57 for
      prostate cancer-specific mortality and 0.56 for total mortality). Among men
      without metastases when diagnosed, higher intake of dairy foods after prostate
      cancer diagnosis may be associated with increased prostate cancer-specific and
      all-cause mortality.

PMID- 25989748
TI  - Induced radioisotopes in a linac treatment hall.
AB  - When linacs operate above 8MV an undesirable neutron field is produced whose
      spectrum has three main components: the direct spectrum due to those neutrons
      leaking out from the linac head, the scattered spectrum due to neutrons produced
      in the head that collides with the nuclei in the head losing energy and the third
      spectrum due to room-return effect. The third category of spectrum has mainly
      epithermal and thermal neutrons being constant at any location in the treatment
      hall. These neutrons induce activation in the linac components, the concrete
      walls and in the patient body. Here the induced radioisotopes have been
      identified in concrete samples located in the hall and in one of the wedges. The
      identification has been carried out using a gamma-ray spectrometer. 

PMID- 25989749
TI  - Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell
      transplantation is associated with lipodystropic and sarcopenic phenotypes.
AB  - BACKGROUND: Survivors of childhood acute lymphoblastic leukaemia (ALL) treated
      with haematopoietic stem cell transplantation and total body irradiation
      (HSCT/TBI) have a high cardiometabolic risk despite lacking overt clinical
      obesity. This study characterised body composition using different methodologies
      and explored associations with reduced insulin sensitivities in a group of ALL
      survivors treated with/without HSCT/TBI. PROCEDURE: Survivors of childhood ALL
      treated with HSCT/TBI (n = 20,10 M) were compared with Chemotherapy-only (n =
      31), and an obese non-leukaemic controls (n = 30). All subjects (aged 16-26
      years) were investigated with: auxology (BMI, waist and hip circumferences), DEXA
      (total and regional fat, fat-free mass), abdominal MRI (subcutaneous, visceral,
      intramuscular fat), oral glucose tolerance tests (impaired glucose tolerance or
      diabetes, insulin sensitivity) and serum adiponectin. RESULTS: HSCT/TBI Group
      displayed a higher prevalence of abnormal glucose tolerance (45%); lower insulin
      sensitivity; lower lean mass with higher prevalence of reduced fat-free mass
      index (from DEXA); higher visceral and intramuscular, and lower subcutaneous fat
      on MRI, compared with the Chemotherapy-only and Obese controls. BMI was lowest in
      HSCT/TBI Group. Waist-to-hip and android-to-gynoid ratios were similar between
      HSCT/TBI and Obese Groups. Insulin sensitivity adjusted for visceral fat mass was
      lower in the HSCT/TBI than the Chemotherapy-only and Obese groups. Adiponectin in
      the HSCT/TBI Group was lower than the Chemotherapy-only group, and correlated
      negatively with time post HSCT/TBI. CONCLUSIONS: HSCT/TBI survivors have an
      increased risk of abnormal glucose tolerance and reduced insulin sensitivity with
      reduced subcutaneous and increased visceral fat distribution, increased total fat
      mass and reduced lean mass.

PMID- 25989751
TI  - The solid state conversion reaction of epitaxial FeF2(110) thin films with
      lithium studied by angle-resolved X-ray photoelectron spectroscopy.
AB  - The phase evolution and morphology of the solid state FeF2 conversion reaction
      with Li has been characterized using angle-resolved X-ray photoelectron
      spectroscopy (ARXPS). An epitaxial FeF2(110) film was grown on a MgF2(110) single
      crystal substrate and exposed to atomic lithium in an ultra-high vacuum chamber.
      A series of ARXPS spectra was taken after each Li exposure to obtain depth
      resolved chemical state information. The Li-FeF2 reaction initially proceeded in
      a layer-by-layer fashion to a depth of ~1.2 nm. Beyond this depth, the reaction
      front became non-planar, and regions of unreacted FeF2 were observed in the near
      surface region. This reaction progression is consistent with molecular dynamics
      simulations. Additionally, the composition of the reacted layer was similar to
      that of electrochemically reacted FeF2 electrodes. An intermediary compound
      FexLi2-2xF2, attributed to iron substituted in the LiF lattice, has been
      identified using XPS. These measurements provide insight into the atomistics and
      phase evolution of high purity FeF2 conversion electrodes without contamination
      from electrolytes and binders, and the results partially explain the capacity
      losses observed in cycled FeF2 electrodes. 

PMID- 25989752
TI  - Vitamin D deficiency and possible link with Bony pain and onset of Osteoporosis.
AB  - OBJECTIVE: To explore if vitamin D deficiency had a direct correlation with bone
      pain or if it contributes in any way to the onset of osteoporosis. METHODS: The
      cross sectional Study was conducted from February to May 2014, presented at
      Liaquat National Hospital, Karachi, and comprised Orthopaedic outpatients. Who
      were questioned, examined and counselled, before a questionnaire was filled that
      included questions about their complaint, and its severity. Several blood test
      reports were incorporated including serum Vitamin D, to evaluate kidney and liver
      functions. Dual energy X-ray absorptiometry scans of the lumber and hip regions
      were also included. Data was collected manually and analysed using SPSS version
      16. RESULTS: The mean age of the 65 subjects, was 52.+/-16 SD years, and
      54(83.1%) were overweight with body mass index of 29.7kg/m2. Besides, 61(93.8%)
      had a positive association of low vitamin D levels as a causative agent for bone
      pain with mean pain severity index 6+/-1 SD. On the other hand 25(38.5%) were
      diagnosed as cases of osteoporosis, and, of them, 21(84%) had low vitamin D
      levels. CONCLUSIONS: Deficiency of vitamin D was directly related to the
      intensity of bone pain. Some patients had vitamin D deficiency along with
      osteoporosis, which may have aggravating effect in this context.

PMID- 25989754
TI  - Competing interests of undergraduate medical education and industry: integration
      into longitudinal curricular themes.
AB  - Recent changes in curricula around the globe with emphasis on teaching/learning
      and assessing professionalism in medical schools has been the priority. With the
      changing public expectations and professional demands, it has become imperative
      to develop clear guidelines and policies for students and faculty to better
      understand and meet the expectations of them as part of professionalism. In order
      to analyse this problem and highlight potential solutions, a literature search
      was conducted using Eric, Medline, Google Scholar and CINAHL Plus databases from
      1985 to February 2013. We reviewed publications regarding the relationship
      between the pharmaceutical and device industry and medical education which is one
      of the most debated and divisive ethical issues. We also analysed the tenets of
      professionalism, including integrity, primary responsibility to our patients,
      self-regulation, and societal responsibility, as they provide the framework to
      make decisions that meet our standards and support the public and patient's faith
      and trust in us. We propose that every lecture to medical students must include a
      standardised disclosure. Role modelling, on-going education, and creating
      policies that eliminate, instead of simply mitigating the negative consequences
      of faculty's conflicts of interest, are specific interventions on which we will
      need to focus to prevent harm to future physicians, and most importantly, to
      patients. 

PMID- 25989753
TI  - Functional outcome of complex tibial plateau fractures managed with closed
      ilizarov.
AB  - OBJECTIVE: To determine the functional outcome of closed Ilizarov treatment in
      complex tibial fractures in terms of range of motion and stability of collateral
      ligaments of knee. METHODS: The descriptive case series was conducted at Ghurki
      Trust Teaching Hospital/Lahore Medical and Dental College, Lahore, from July 21,
      2012, to January 20, 2013. After evaluation according to advance trauma life
      support protocol, patients were selected to undergo close Ilizarov. They were
      followed up for 3 months and functional outcome in terms of range of motion and
      stability was assessed. We went above-knee if ligaments were torn and the knee
      was unstable. The above-knee assembly was removed after 6 weeks and tibial
      fixator was removed at 12 weeks. Subject to fracture healing, full weight-bearing
      was started 2-4 week later. SPSS 17 was used for statistical analysis. RESULTS:
      Of the40 patients in the study, 33(82.5%) were males and 7(17.5%) were females
      with a mean age of 36.68+/-11.77 years (range: 15-55 years). Overall, 36(90%)
      patients had range of motion graded good to excellent, while and 37 (92.5%) had
      stability graded good to excellent. CONCLUSIONS: Ilizarov fixation is an ideal
      method of treatment for tibial plateau fractures when extensive dissection and
      internal fixation are contraindicated due to trauma to the soft tissue,
      deficiency of bone stock, and bony comminution.

PMID- 25989755
TI  - Decreased bone mineral density and associated risk factors in hospital visiting
      people of Islamabad.
AB  - OBJECTIVE: TBesides aging there are multiple factors involved in decreasing Bone
      Mineral Density. Knowing the burden of the diseaseand its related factors in our
      population can help better treat this. Therefore, our objective was to identify
      subjects with low Bone Mineral Density (BMD) and its risk factors in hospital
      visiting people in Islamabad. METHODS: Descriptive cross sectional study was
      conducted atRawal Institute of Health Sciences, Islamabad in 3rd week of June,
      2014. Total 300 persons including patients, attendants and hospital staff were
      selected.Calcaneus BMD was measured usingultrasound bone densitometer. T-score
      was calculated.Specific questionnaire form was filled to identify risk factors.
      Prevalence and prevalence ratio was calculated. RESULTS: Out of 300 study sample,
      178 (59.3%) are females. Mean age of the study population is 37.34 (SD=12.93).
      Overall, prevalence of osteopaenia and osteoporosis in the study population is
      107 (35.7%) and 5 (1.7%) respectively. Prevalence of osteopaenia is seen more in
      elderly subjects, females, people with low Body Mass Index (BMI), people who are
      usually not exposed to sunlight and who are mostly bound to houses. CONCLUSIONS:
      Decreased BMD is associated with increasing age, female gender, low BMI, little
      exposure to sun light and being restrained to homes. It is not affected by daily
      milk intake, parity of females, cola drinking and smoking in our part of the
      world.

PMID- 25989756
TI  - Pseudomonas as trespassers in diabetic foot infections: More questions and fewer
      answers.
AB  - OBJECTIVE: To assess microbiological isolates from diabetic foot ulcers presented
      at a tertiary care teaching hospital. METHODS: The prospective observational
      study was conducted at department of Orthopaedics, Liaquat National Hospital
      Karachi, from January 2009 to October 2011, and comprised patients with diabetic
      foot ulcers (Wagner grading 1-4). Grade 0 and 5 were excluded. Wound swabs or
      tissue biopsies were taken before the induction of antibiotic prophylaxis
      according to the standard aseptic protocols. SPSS 16 was used for statistical
      analysis. RESULTS: Of the 250 patients in the study, 151(60.4%) were male with an
      overall mean age of the subjects of 46+/-8.1 years. Mean duration of diabetes was
      14+/-6.7 years. Based on Wagner's grading, 90(36%) patients had grade 1,
      58(23.2%) grade 2, 97(38.8%) grade 3, and 5(2%) grade 4. The most common isolates
      were polymicrobial in 90(36%) patients and pseudomonas aeruginosa in 87(34.8%).
      Resistance antibiogram for pseudomonas aeruginosa showed sensitivity against
      Imipenem, Aztreonam, Ceftazidime, Ciprofloxacin and Gentamicin. CONCLUSIONS: The
      isolation of pseudomonas aeruginosa gives an idea about the recent microbial
      spectra from our region and should prompt the need for multi-centre studies from
      South Asia to devise treatment guidelines for this part of the world.

PMID- 25989757
TI  - Operative management of patients with non-spinal metastatic bone disease. Does it
      actually improve quality of life?
AB  - OBJECTIVE: To determine the survival rate and functional outcome of skeletal
      stabilisation in patients with metastatic bone disease. METHODS: The
      retrospective study was conducted at Aga Khan University Hospital, Karachi, and
      comprised data of patients with non-spinal metastatic bone disease managed
      surgically from January 2002 to December 2010. All patients had been managed by
      experienced orthopaedic, oncology and multidisciplinary teams. Patients managed
      by non-oncologic orthopaedic surgeons were excluded. The prognostic influence of
      clinical, pathological and treatment variables on Musculoskeletal Tumour Society
      score, range of motion, local complications and death rate were measured. SPSS 19
      was used for statistical analysis. RESULTS: Of the 49 patients whose records were
      included in the study, 21(42.9%) males and 28(57.1%) females with an overall
      median age of 59 years. Most common primary tumour site was breast in 15(3.8%)
      followed by lungs in 11(22.4%), Open reduction and internal fixation was the mpst
      commonly used procedure in 18(36.7%) patients. Mean duration of follow-up was
      30.20+/-29.2 SD months (range: 10-48 months). The median patient survival was 23
      months. 23% patients have superficial surgical site infection. Mean
      Musculoskeletal Tumour Society score was 23.73+/-14.3 SD. CONCLUSIONS: The
      results confirm the principle that surgery for metastatic disease is done
      primarily to improve quality of life and ambulation status, and to alleviate
      pain.

PMID- 25989758
TI  - Bone mineral density in patients with chronic backache.
AB  - OBJECTIVE: To evaluate the association of bone mass density with chronic
      backache. METHODS: The case-control observational study was conducted at Bone
      Mass Density Assessment Unit, Liaquat University of Medical & Health Sciences
      Jamshoro from January 2011 to December 2013. Adult patients of either gender
      having chronic backache were studied alongside subjects without backache who
      served as the control group. Bone mass density of all patients was measured at
      the lumbar spine (L1-L4) and hip using a dual-energy X-ray absorptiometry scan.
      Association of chronic backache with age, gender, body mass index and bone mass
      density was assessed by performing multiple regression analysis. RESULTS: Of the
      482 subjects in the study, 162(33.6%) were cases and 320(66.3%) were the
      controls. Overall age range was 20-78 years with a mean of 48.5+/-12.36. The mean
      age of the controls was 38.87+/-13.55, while for the cases it was 36.26+/-9.41.
      Bone mass density in the cases was significantly low compared to the controls (p
      0.028). CONCLUSIONS: Severity of chronic backache could be predicted by low bone
      mass density.

PMID- 25989759
TI  - Significance of strontium ranelate in healing of surgically fixed tibial
      diapyseal fractures treated with strontium ranelate vs placebo; a randomised
      double blind controlled trial.
AB  - OBJECTIVE: To determine the surgical outcome of patients with axial cervical
      spine fractures. METHODS: The randomised double-blinded placebo-controlled
      clinical study was conducted at the Indus Hospital, Karachi, from August 2011 to
      August 2013. Patients were randomised to receive placebo or strontium ranelate
      postoperatively after surgical fixation of tibial diaphyseal fractures.
      Assessment of fracture healing was done clinically and radiologically at 30, 60
      and 90 days. SPSS 21 was used for statistical analysis. RESULTS: Initially, 76
      patients were enrolled, but 63(82.9%) completed the study. Out of 63 patients,
      32(50.8%) were randomly assigned to group A and 31(49.2%) to group B, which was
      administered the placebo. Overall enhancement of fracture healing efficacy of
      strontium ranelate group was 20(62.5%) versus 9(29%) of the placebo group.
      CONCLUSIONS: Strontium ranelate was effective in enhancing fracture healing based
      on clinical and radiological assessment. Hence, it can be considered an effective
      therapeutic agent for accelerating fracture healing.

PMID- 25989760
TI  - A comparison between orthopedic surgeon and allied health worker in pirani score.
AB  - OBJECTIVE: To assess the strength of agreement for each of the Pirani assessment
      categories between an orthopaedic surgeon and allied health worker on scoring
      clubfeet. METHODS: The descriptive cross-sectional study was conducted at the
      Indus Hospital, Karachi, from November 2012 to June 2013, comprised children
      below 12 months of age with untreated unilateral or bilateral clubfoot deformity
      an allied health worker, who was a plaster technician, was given 1-week training
      in the Pirani Scoring method. The feet were scored by the surgeon and the
      paramedic independently. SPSS 21 was used for statistical analysis. RESULTS: The
      study had 57 patients, and 92 feet were assessed. The difference between the
      means of score of each parameter, including the hind foot score and total score,
      was less than 0.09. The means of total score were found to be identical. Total
      Hind Foot Score was 0.48 and Total Score was 0.354. The statistical inter
      observer reliability for all components was rated as substantial to moderate
      agreement except Equinus Rigidityand Total Score, which showed fair agreement.
      CONCLUSIONS: Pirani scoring method for clubfoot assessment was found to be a
      reliable tool for use by plaster technicians for independent assessment of
      clubfoot. However, prior training and supervision in the early phase is
      necessary.

PMID- 25989750
TI  - Purinergic signalling during development and ageing.
AB  - Extracellular purines and pyrimidines play major roles during embryogenesis,
      organogenesis, postnatal development and ageing in vertebrates, including humans.
      Pluripotent stem cells can differentiate into three primary germ layers of the
      embryo but may also be involved in plasticity and repair of the adult brain.
      These cells express the molecular components necessary for purinergic signalling,
      and their developmental fates can be manipulated via this signalling pathway.
      Functional P1, P2Y and P2X receptor subtypes and ectonucleotidases are involved
      in the development of different organ systems, including heart, blood vessels,
      skeletal muscle, urinary bladder, central and peripheral neurons, retina, inner
      ear, gut, lung and vas deferens. The importance of purinergic signalling in the
      ageing process is suggested by changes in expression of A1 and A2 receptors in
      old rat brains and reduction of P2X receptor expression in ageing mouse brain. By
      contrast, in the periphery, increases in expression of P2X3 and P2X4 receptors
      are seen in bladder and pancreas. 

PMID- 25989761
TI  - Perception about braces in parents of children with clubfoot.
AB  - OBJECTIVE: To access the acceptability of Steenbeek brace by children undergoing
      clubfoot correction and their parents to ensure long-term compliance. METHODS:
      The cross-sectional study was conducted at the Indus Hospital, Karachi from
      October 2013 to March 2014. A trained researcher interviewed the person primarily
      responsible for bracing the child using a pre-coded questionnaire. Modified
      Orthotics Prosthetics User Survey for satisfaction with either the Mitchell brace
      of the Steenbeek brace was used. It included 11 questions in the Parent Bracing
      Satisfaction Survey. SPSS 21 was used for statistical analysis. RESULTS:
      Interviews were completed with 110 primary caregivers among whom 90(81.8%) were
      mothers. Overall, 32(29.1%) children were using the Mitchell brace, 30(27.3%) the
      Steenbeek brace, 46(41.8%) had shifted from Mitchell to Steenbeek brace, and
      2(1.8%) had shifted from Steenbeek to Mitchell brace. Median duration of current
      brace usage was 4 and 3.5 months for Steenbeek and Mitchell braces respectively.
      The mean age of the child was 1.4 +/-0.7 years, and the mean of 4-point Likerts
      cale score of parent bracing satisfaction was 28.7+/-2.2 in children on the
      Mitchell brace versus 28.5+/-1.9 for those on Steenbeek brace (p=0.505). Overall,
      82(74.5%) parents had favourable attitude towards braces in general, but there
      were no significant differences in the items except "brace is easy to put on"
      (p=0.040) and "durability between Mitchell and Steenbeek groups" (p=0.017).
      CONCLUSIONS: There were no differences in satisfaction levels between the two
      types of brace users.

PMID- 25989763
TI  - Our experience with Van Nes Rotationplasty for locally advanced lower extremity
      tumours.
AB  - OBJECTIVE: To present an early experience with the time-tested technique of Van
      Ness Rotationplasty to save distal lmbs. METHODS: Van Nes Rotationplasty for
      locally advanced lower extremity tumours. A reterorespective audit was conducted
      at Aga Khan University Hospital, Karachi, and comprised cases of bone and soft
      tissue sarcoma who underwent Van Ness Rotationplasty over seven years from
      January 2005 to December 2011. Demographic data, family history, past history, co
      morbids, date since diagnosis, duration of symptoms, type of tumour, metastasis,
      pre-op and post-op functional status, recurrence and survival were collected.
      RESULTS: Of the 351 cases of bone and soft tissue sarcoma, 9 (2.6%) underwent Van
      Ness Rotationplasty and were included in the study. The mean duration of symptoms
      was 7+/-3SD months (range: 8-41 months). All except 1(11.1%) were osteogenic
      sarcomas. All except 1(11.1%) involved distal femur. Overall, 7(77.8%) had
      localised Enneking stage IIB disease. Two (22.2%) patients expired due to
      metastatic disease, but none had local recurrence. Complete excision of tumour
      was achieved in all (100%) patients. Longest follow-up was of 34 months while the
      shortest was of 6 months. No local recurrences were noted. Functional recovery
      was good. Two (22.2%) patients had simultaneous sciatic nerve repair as part of
      the primary procedure. Both of them had good motor function at the time of final
      follow-up. Mean Musculoskeletal Tumour Societyscore was 23.88+/-2SD. CONCLUSIONS:
      Van Nes Rotationplasty was found to be a successful alternative to amputation in
      cases of locally advanced tumours of distal femur or proximal tibia.

PMID- 25989762
TI  - Functional and radiological outcome of Intramedullary nailing vs. plate fixation
      for humeral shaft fractures. Does treatment method bring any difference?
AB  - BACKGROUD: Operative Management of Humeral shaft fractures may be accomplished
      with the help of Plate fixation or IM Nails. Controversy exists as to which
      modality is superior to the other in terms of fewer complications and better
      functional and radiological outcome. OBJECTIVE: To compare the differences in
      radiological and functional outcome of humeral shaft fractures managed by
      platefixation and antegrade intramedullary nails. METHODS: The retrospective
      study was conducted at Aga Khan University Hospital, Karachi, and comprised
      records of Patients managed surgically for uncomplicated humeral shaft fractures
      between 2007 and 2012. The patients were followed up for one year at clinic, and
      radiographs and clinical assessment were used to complete the Quick Disabilities
      of the Arm, Shoulder and HandQuestionnaire. SPSS 19 was used for statistical
      analysis. RESULTS: Of the total 61 patients, 39(64%) underwent plating and
      22(36%) had intramedullary nailing. There was no significant difference in terms
      of mean age and mean duration of surgery in the two groups (p>0.05 each). Also,
      no significant difference was noted in the duration of healing with either of the
      two methods (p>0.05). Mean Questionnaire score for plating was 23.9+/-17.7, while
      for intramedullary nailing it was 21.7+/-19.8 (p>0.05). CONCLUSIONS: There was no
      significant difference in the radiological and functional outcome of patients in
      the two groups.

PMID- 25989764
TI  - Transfusion practice in orthopedic patients: do we really need it?
AB  - OBJECTIVE: To determine the proportion of inappropriate transfusions in patients
      undergoing orthopaedic surgery at a tertiary care university hospital, and
      factors associated with inappropriate transfusions. METHODS: The prospective
      study was conducted at Aga Khan University Hospital, Karachi, from December 2008
      to September 2009, and comprised patients admitted to the Orthopaedic Department
      and received transfusion of at least one packed cell. Patients were divided into
      four groups: A, those with haemoglobin < 7, B, haemoglobin 7.1-10 without
      ischemic heart disease, C, haemoglobin 7.1-10 with ischemic heart disease, and D,
      haemoglobin >10. Variables recorded were, pre-transfusion haemoglobin level, co
      morbids, symptoms of hypovolemia, pre-transfusion volume replacement with fluids,
      transfusion reactions, and haemoglobin after 48 hours. Indications of transfusion
      were assessed in accordance with available data. RESULTS: Of the 126 patients,
      65(52%) were males and 61(48%) were females. There were 18(14%) patients in group
      A, 88(70%) in group B, 12(10%) in group C, and 8(6%) in group D. Overall,
      Overall, 44(35%) were transfused appropriately according to the criteria, and
      82(65%) were inappropriate. CONCLUSIONS: The number of inappropriate transfusion
      was quiet high and demands revision of institutional policy of packed cell
      transfusion in accordance with available guidelines.

PMID- 25989765
TI  - Use of distally based random flap in the management of soft tissue defects in
      upper two thirds of leg.
AB  - OBJECTIVE: To assess the results of cases with complex wounds exposing tibia who
      were managed with distally based random flaps. METHODS: The retrospective study
      was conducted at Aga Khan University Hospital, Karachi, and Dow University
      Hospital, Karachi and comprised data between February 2000 and March 2013of
      patients who had been admitted with a recent or prior history of trauma with a
      soft tissue defect in upper two-thirds of tibia and who had undergone coverage
      procedure using distal based flap. RESULTS: The mean age of the total 21 patients
      in the study was 29+/-9 years, and 20(95%)were male. Road traffic accident was
      the most common mechanism of injury in 13(62%). Tibia was exposed in all the
      21(100%) cases requiring soft tissue coverage. There was associated fracture of
      tibia in 18(86%) patients. Mean flap length was 12+/-1.7 cm and width was 5.3 +/
      0.86 cm. Maximum size for the flap dissected was 15x7cm. Donor site was covered
      with split thickness skin graft in 19(90.5%) patients. Flap survival rate was
      100%. Only 2(9.5%) patients developed partial flap necrosis. Clinical outcome was
      graded as good in 19(90.5%) patients and fair in 2(9.5%). Superficial infection
      was observed in 2(9.5%) patients. CONCLUSIONS: Distal based flap appeared to be
      an effective solution for the coverage of soft tissue defects in upper two-thirds
      of leg.

PMID- 25989766
TI  - Use of fresh parental fibular allograft for reconstruction of skeletal defects
      after limb salvage surgery.
AB  - OBJECTIVE: To share early experience with paediatric patients having undergone
      skeletal reconstruction after limb salvage surgery. METHODS: A reterorespective
      audit study was conducted at Aga Khan University Hospital, Karachi, from 1994 to
      2011 An audit of the institutional tumour registry was done and relevant cases of
      paediatric patients having undergone skeletal reconstruction after limb salvage
      surgery were tracked. Outcomes were objectively assessed through Musculoskeletal
      Tumour Society score. International Society of Limb Salvage grading was used to
      measure union of the graft to the host bone. RESULTS: Of the total 9 patients,
      5(55.6%) were males and 4(44.4%) were females with an overall mean age of 11+/-3
      SD years (range: 7-14 years). Six (66.7%) cases involved lower limbs, while
      2(22.2%) cases involved upper limbs. The mean follow-up was 41+/-3SD months
      (range: 14-204 months). There was no tissue reaction observed locally or
      systemically. No local recurrence was seen. Mean Musculoskeletal Tumor Society
      score was 21.2+/-3 SD and International Society Of Limb Salvage grading was
      excellent in 5(55.5%) patients and good in 2(22.2%). One (11.1%) fibula fractured
      due to non-union at the proximal site. One (11.1%) patient died of the disease.
      Donor site morbidity was minimum except a big toe drop in 1(11%) case.
      CONCLUSIONS: Parental fresh fibular allografts provide a good alternative for
      skeletal reconstruction. Donor site morbidity was minimal.

PMID- 25989767
TI  - Role of injecting bone marrow aspiration injection in treating delayed union and
      non-union.
AB  - OBJECTIVE: To access the role of bone marrow injection in the management of
      delayed union and non-union. METHODS: The prospective study was conducted at the
      Department of Orthopaedic Surgery and Traumatology, Mayo Hospital, Lahore, from
      January 2012 to December 2013, and comprised patients who had long bone fractures
      that resulted in delayed or non-union and were treated with bone marrow
      injections. Aspiration of bone marrow was done from tibial tuberosity and was
      injected percutaneously at the fracture site. The whole procedure was carried out
      as a day case. Fracture site mobility, tenderness and radiological features were
      assessed using the Union Scale score. RESULTS: Of the 25 patients, 18(72%)were
      male and 7(28%) were female with an overall mean age of 38+/-12.96SD years
      (range: 17-61 years). There were 19(76%) tibial shaft fractures, 4(16%) had shaft
      of femur fracture, and 2(8%) had humeral shaft fracture. Mean time duration
      between the injury and the procedure was 34 +/-3.46 SD weeks (range: 30-42
      weeks). Overall, 23 (92%) patients showed union and the mean time of healing was
      15 +/-2.73SD weeks (range: 12-22 weeks) after the procedure. CONCLUSIONS:
      Percutaneous bone marrow injection provided an alternative to open bone grafting,
      having least complications, especially for early intervention in the fracture
      healing process.

PMID- 25989768
TI  - Variability of magnification on digital pelvic radiographs from patients with
      fractures of the femoral neck - a retrospective audit.
AB  - OBJECTIVE: To determine the variability in magnification of radiographs in an
      emergency setting. METHODS: The retrospective study was conducted at Aga Khan
      University Hospital, Karachi, and comprised records of patients who underwent
      Austin Moore hemiarthroplasty over a two-year periodfrom 1st January 2006 to 31st
      December 2007. Magnification factor was determined using measurements obtained
      from preoperative and postoperative radiographs and comparing them with the
      actual size of implant used. Intra-observer and inter-observer reliability of
      measurements were calculated. SPSS 19 was used for data analysis. RESULTS: Of the
      63 patients studied, 25(39.7%) were males and 38(60.3%) were females with an
      overall mean age of 69.8+/-12 years. The mean implant size used was 46mm+/-4mm.
      Preoperative magnification was 8%+/-4%, resulting in an overestimation of implant
      size by 4.2+/-2.3mm. Postoperative magnification was 13%+/-4%, resulting in an
      overestimation of 5.9+/-1.9mm.Prediction using fixed scaling of 15% resulted in a
      correct estimation of implant size for only 15(24%) patients. CONCLUSIONS:
      Digital radiographs of the pelvis exhibited variable amount of magnification
      along with an inconsistency in magnification on repeat examination.

PMID- 25989769
TI  - Operative treatment of displaced intra-articular fractures of Calcaneum: Is it
      worthwhile?
AB  - OBJECTIVE: To compare the results of operative treatment for displaced intra
      articular fractures of calcaneum with conservative treatment. METHODS: The
      retrospective non-randomised comparative study using. purposive non-probability
      convenient sampling was conducted at the Combined Military Hospital, Rawalpindi,
      and comprised treatment records from March 2010 to October 2013 of patients who
      had been treated either by Plaster of Paris casting (Group A) or managed by open
      reduction internal fixation (Group B). Functional outcome was assessed using Foot
      and Ankle Disability Index. RESULTS: Of the 42 records in the study, 20(47.6%)
      related to Group A and 22(52.4%) to Group B. The mean age was 41+/-7.82 years
      (range: 28-55 years) in Group A, and 31+/-6.35 years (range: 21-43) in Group B.
      Male-to-female ratio was 10:1 in Group A; 9:1 in Group B. Union was achieved in
      all (100%) cases. Bone substitute was used in 16(72.7%) in Group B to fill void
      during reconstruction of collapsed calcaneum. Wound complications were noted in
      2(9.1%) Group B patients. There was loss of reduction in 1(4.5%). Mean Foot and
      Ankle Disability Index score in Group A was 45+/-10.68.4 compared to 67.9+/-10.04
      in Group B (p=1.99). CONCLUSIONS: For displaced intra-articular fractures,
      operative treatment is associated with better functional outcome in terms of
      absolute functional scores and should be the treatment of choice although factors
      such as age, soft tissue injury and surgical expertise may influence the
      decision.

PMID- 25989771
TI  - Burkhalter opponensplasty; role in isolated median nerve injury.
AB  - OBJECTIVE: To report the outcome of Burkhalter opponensplasty using Extensor
      Indicis Proprius with isolated traumatic low median nerve palsy. METHODS: The
      prospective study was conducted at the Mayo Hospital, Lahore, from June 2010 to
      June 2013, and comprised cases of Burkhalter opponensplasty using the Extensor
      Indicis Proprius to restore thumb opposition in isolated median nerve palsies.
      All patients had the condition for 16 to 20 months. The tendon was harvested just
      proximal to the extensor expansion and the insertion was to the distal attachment
      of abductor pollicis brevis. RESULTS: Of the 11 patients in the study, 6(54.5%)
      were females and 5(45.5%) were males, with overall ages ranging between 19 years
      and 51 years. There were no postoperative complications. Nine (82%) patients had
      excellent results, while the remaining 2(18%) had good result. CONCLUSIONS: In
      patients with isolated traumatic median nerve palsy, Burkhalter opponensplasty
      yielded excellent and satisfactory results.

PMID- 25989770
TI  - Outcome of neurolysis combined with anterior submuscular transfer of ulnar nerve
      in McGowan Grade II and III tardy ulnar nerve palsy.
AB  - OBJECTIVE: To see the impact of combined neurolysis and submuscular transposition
      approach in patients with tardy ulnar nerve palsy of Mc Gowan grades II and III.
      METHODS: The descriptive case series was conducted at King Edward Medical
      University, Mayo Hospital, Lahore, between January 2013 and January 2014, and
      comprised patients with positive nerve conduction study and electromyography,
      aged above 14 years with McGowan grades II and III tardy ulnar nerve palsy of any
      aetiology. They were treated by a single surgeon and his team. Anterior
      submuscular transposition with internal neurolysis under loupes was performed.
      Improvement in hand function was determined with Quick Disabilities of the Arm,
      Shoulder and Handscore 6 months postoperatively. Data was analysed using SPSS 16.
      RESULTS: Of the 20 consecutive patients in the study, 14(70%) were males and
      6(30%) were females with a standard deviation of 16.35(range: 14-60 years). Six
      month postoperatively, Quick Disabilities of the Arm, Shoulder and Handscore had
      a mean improvement from 43 to 21 (standard deviation from 6.46 to 7.51)
      supporting the evidence that 18(90%) patients had significant improvement in hand
      function. There was 1(5%) excellent, 13(65%) good, 4(20%) fair and 2(10%) poor
      functional outcomes. CONCLUSIONS: Patients with Mc Gowan grades II and III tardy
      ulnar nerve palsy showed good functional outcome when internal neurolysis was
      combined with submuscular transposition.

PMID- 25989772
TI  - Chondromyxoid fibroma; experience of 36 cases of an intriguing entity.
AB  - OBJECTIVE: To evaluate the clinico-pathological features and treatment options of
      chondromyxoid fibroma patients. METHODS: The retrospective study was conducted at
      the Aga Khan University Hospital (AKUH), Karachi, and comprised data of all cases
      of chondromyxoid fibroma of bone diagnosed between 1996 and 2013.The diagnosis
      had been made mostly histopathologically, but also included patients in whom
      preoperative incisional biopsies had been used. Histopathological and
      radiological findings along with various treatment options and follow-up was
      recorded on a proforma. RESULTS: Of the total 36 patients,14(39%) were females
      and 22(61%) were males, with an overall mean age +/- of standard deviation 20.9
      years +/- 9.8 (range: 6-51 years). Diagnosis was made histopathologically in
      27(75%) patients and biopsy was used in 9(25%) cases. The most common site of
      involvement was tibia in 16(44.4%). The main presenting symptom was pain in
      30(83.3%) and/or swelling in 6(16.6%). Radiological examination revealed no foci
      of soft tissue involvement. Bizarre large atypical cells were seen in 14(39%)
      cases and osteoid formation in 2(5.5%), leading to extreme difficulty in
      diagnosis. Treatment options included wide resection and marginal excisionin
      22(61%) cases, intra-lesional curettage in 14(39%). The mean +/- standard
      deviation follow-up was 48.8 +/- 40.2 months (range: 8-152 months). Follow-up
      details were available only for 19(53%) patients. Among them, recurrence occurred
      in 7(36.8%) patients. No functional loss developed after surgical treatment, but
      3(16%) patients developed wound-site infection. CONCLUSIONS: Chondromyxoid
      fibroma is clinically and histopathologically rare and difficult to diagnose
      because of the absence of typical diagnostic features in every case.

PMID- 25989773
TI  - Malrotation after reamed intramedullary nailing with and without a fracture table
      for closed fractures of the femoral shaft.
AB  - OBJECTIVE: To observe the effect of the choice of surgical table on the incidence
      of malrotation. METHODS: The randomised trial was conducted from July 2012 to
      January 2013 at the Aga Khan University Hospital, Karachi, during which 74
      patients were inducted. Randomisation was done via random allocation software
      version 1.0.0 and sealed envelopes were used to guide the choice of table.
      Malrotation was assessed by the operating surgeon using the lesser trochanteric
      shape signunder intra-operative fluoroscopy. SPSS 19 was used for statistical
      analysis. RESULTS: The 74 patients in the study were divided into two groups of
      37(50%) each using fracture table and the regular table.Overall, there were
      55(74%) male and 19(26%) female patients with a mean age of 37+/-17 years.
      Overall incidence of malrotation was 13(17.6%). Malrotation was observed in
      7(19%)patients in the fracture table group and 6(16%)in the regular table group
      (p=0.760). CONCLUSIONS: The choice of fracture table did not influence the
      occurrence or direction of malrotation.

PMID- 25989774
TI  - Outcome of single stage vertebral column resection in treatment of kyphotic
      deformity.
AB  - OBJECTIVE: To find the frequency of deformity correction, functional outcome and
      complications of single-stage vertebral column resection in patients with
      kyphotic deformity. METHODS: The prospective case series was conducted at
      Hayatabad Medical Complex, Peshawar, and Aman Hospital, Peshawar, from January
      2012 to December 2013, and comprised all patients who underwent single-stage
      posterior vertebral column resection. Only patients with severe rigid sharp
      deformity of different aetiology that required more than 40 degree correction and
      who had at least 3-month follow-up were included. Data was processed using SPSS
      16. RESULTS: Of the total 18 patients, 11(61.1%) were male and 7(38.9%) were
      female, with an overall mean age of 28.7+/-13.6 years (range: 12-60 years). Among
      them, 8(44.4%) patients had congenital kyphosis, 5(27.8%) had posttraumatic
      origin, 4(22.2%) had post-tuberculous deformity, while 1(5.6%) had iatrogenic
      kyphosis. The apex of the deformity was in thoracic spine in 12(66.7%) patients,
      while in 6(33.3%) patients it was in the lumbar spine. The average pre- and post
      operative Cobb's angle was 66.2+/-18.9 degrees and 18.8+/-12.8 degrees
      respectively. Mean correction of deformities was 47.3+/-13.3 degrees. The mean
      correction achieved in percentage terms was 73.5+/-8.6 per cent (range: 56-87%).
      There were no patients with post-operative deterioration of neurological status.
      Two (11%) patients underwent re-exploration of the wounds with wash and cultures
      due to wound discharge. CONCLUSIONS: Posterior vertebral column resection was
      found to be a very effective method of correction of severe kyphotic deformities
      in expert hands with acceptable morbidity.

PMID- 25989775
TI  - Is smartphone a necessity or luxury among orthopedic specialty?
AB  - OBJECTIVE: To assess the utilisation pattern of smart phones by residents and
      consultants with respect to their clinical work and academics. METHODS: The cross
      sectional study was carried out in orthopaedic departments of various hospitals
      in Karachi in July 2014. Orthopaedic residents and consultants were asked to fill
      a questionnaire containing various questions, including utilisation of their
      smart phones for professional applications, books, internet and emails; and
      sharing of clinical data. RESULTS: A total of 98residents and consultants were
      approached and 83(84.7%) of them filled up the questionnaire. Of them, 70(84.3%)
      owned a smart phone and represented the study sample. Of them, 60(85.7%) were
      using applications on their mobile phone; and 27(38.6%) were using them for
      sharing clinical data with colleagues. The use of smart phone applications was
      more among residents than consultants (p=0.010) and the same applied to data
      sharing (p=0.028). AO Surgery reference was the most utilised application in
      43(61.4%). Besides, 46(65.7%) respondents were using smart phones to read text
      books; 60(85.7%) were using internet on their smart phones for browsing web pages
      and to check emails; and 62(88.6%) wanted to have more applications available
      related to orthopaedic practice. Only 1(1.4%) respondent was willing to pay for
      these applications. CONCLUSIONS: Majority of orthopaedic caregivers owned a smart
      phone, but their clinical use was limited which may be enhanced to improve
      patient care.

PMID- 25989776
TI  - Effect of teriparatide on bone regenerate after distraction osteogenesis.
AB  - OBJECTIVE: To determine the effect of teriparatide on new bone formation in a rat
      model of distraction osteogenesis. METHODS: The experimental study was conducted
      at the Aga Khan University Hospital, Karachi, in November-December 2010, and
      comprised male Sprague-Dawley rats weighing 250gm each who were allocated to two
      treatment groups, teriparatide and saline, both given subcutaneously for 7 weeks.
      Femoral distraction was done for 3 weeks at the rate of 0.4mm/day, followed by a
      further 4 weeks for consolidation. New bone formation was assessed using X-ray
      scoring system, bone densitometry and histology. RESULTS: The 12 rats in the
      study were divided into two groups of 6(50%) each. All rats in the teriparatide
      group showed new bone formation whereas bone formation was present only in
      2(33.3%) rats in the saline group. Bone densitometry showed that area (size) of
      the new bone formed adjacent to the margins of the osteotomy site as well as the
      total bone mineral content of the new bone was significantly higher (p<0.05) in
      the teriparatide group. Histological analysis showed larger but statistically
      insignificant (p>0.05) area of woven and trabecular new bone in the teriparatide
      group. CONCLUSIONS: The results suggested a promising role of parathyroid
      analogue therapy in distraction osteogenesis for promoting bone formation and
      consolidation. This may have strong clinical implications in cases of limb
      lengthening and bone transport.

PMID- 25989777
TI  - Results of injection corticosteroids in treatment of De Quervain's Tenosynovitis.
AB  - BACKGROUND: De Quervain's tenosynovitis is defined as stenosing tenosynovitis of
      the synovial sheath of tendons of abductor polices longus and extensor pollicis
      brevis in the first compartment of wrist due to repetitive use. OBJECTIVE: To
      assess the results of injecting corticosteroids injections for De Quervain's
      tenosynovitis. METHODS: 80 patients with disease were included in this study. All
      had a mean of 5.87 weeks of treatment of the condition with NSAIDs and had shown
      no response. Using Visual analogue scale the severity of tenderness on first
      dorsal compartment and pain felt on Finkelstein test was recorded. A mixture of 1
      ml (40mg) of methylprednisolone acetate and 1 ml of 2% lignocaine hydrochloride
      was injected in first dorsal compartment of involved wrist. Patients were
      followed for 28 weeks on monthly basis. Outcome measure was reduction in pain and
      tenderness on the radial side of wrist and negative Finkelstein test subsequent
      to injection. RESULTS: 65% patients after 1st injection were symptoms free at two
      weeks, 35% patients were given second injection two weeks after the first. 80%
      patients at four weeks, 95% patients at six weeks and 98.75% patients were
      symptom free at 12th week. One patient underwent surgical release. The adverse
      reaction of steroid was seen in 25% of patients, which were subsided in 20 weeks.
      CONCLUSIONS: We conclude that two or three local steroid injections in the first
      dorsal compartment lead to significant improvement in patients with de Quervain's
      tenosynovitis.

PMID- 25989778
TI  - Asymptomatic urinary tract infection: Cause of postoperative wound infection.
AB  - OBJECTIVE: To determine the rate of urinary tract infection in patients given
      incomplete treatment before undergoing hip fracture surgery. METHODS: The
      descriptive case series was conducted at Aga Khan University Hospital, Karachi,
      From October 25, 2012 to April 24, 2013. 84 postmenopausal women having hip
      fracture along with asymptomatic urinary tract infection. The infection was
      treated incompletely and postoperatively wound infection rate was determined. The
      SPSS version 17 was used to analyze the data. RESULTS: The overall mean age of
      the 84 patients in the study was 63.57+10.34 years. Overall, 14(16.7%) patients
      had wound infection after orthopaedic implant surgery for hip fracture.
      CONCLUSIONS: There was a high occurrence of wound infection after hip implant
      surgery in patients having preoperative asymptomatic urinary tract infection who
      were treated incompletely.

PMID- 25989779
TI  - Autologous blood injection in the treatment of lateral epicondylitis.
AB  - OBJECTIVE: To determine mean decrease in visual analogue pain score after
      autologous blood injection in patients with lateral epicondylitis. METHODS: The
      quasi-experimental study was conducted at Ghurki Trust Hospital, Lahore, from
      December 10, 2012, to June 8, 2013, and comprised patients having lateral
      epicondylitis of elbow. Pre-procedure baseline visual analogue score was
      measured. Under aseptic conditions, 2ml of autologous blood was drawn from the
      contra-lateral antecubital fossa of the patient and slowly injected into the site
      of maximum tenderness. Patients were advised to continue their normal daily
      activities and were followed up at third and sixth week for assessment of pain
      intensity. Mean decrease was calculated by subtracting the post-procedure visual
      analogue score from the baseline value.SPSS 11 was used for data analysis.
      RESULTS: Of the 150 patients in the study, there were 127(84.7%) males and
      23(15.3%) females. Male-to-female ratio was 5.5:1 Overall mean age of was 33.91+/
      10.23 years. The mean pre-injection pain score was 8.97+/-1.02 and post-injection
      was 3.59+/-1.58. Mean decrease in VAS pain score was 5.37+/-1.80. CONCLUSIONS:
      Autolgous blood injection was found to be an effective way to treat patients of
      epicondylitis elbow.

PMID- 25989780
TI  - Preventing the preventable: role of transamine in total knee arthroplasty.
AB  - OBJECTIVE: To assess the efficacy and safety of perioperative intravenous
      Tranexamic Acid in reducing blood loss and transfusion requirements in patients
      undergoing Total Knee Arthroplasty. METHODS: The prospectivedouble-blind
      randomised control trial was conducted from March to July 2014 at the Combined
      Military Hospital, Rawalpindi, and comprised patients below 85 years of age
      undergoing unilateral or bilateral cemented Total Knee Arthroplasty. The patients
      were divided into control or Transaminegroups. Two doses of 15mg/kg of Transamine
      were given to the latter group. All patients were operated under spinal or
      combined spinal-epidural anaesthesiausing pneumatic tourniquet and similar
      cemented implant. Primary outcome was postoperative blood loss in drains.
      Secondary outcomes were the number of blood units transfused, change in
      haemoglobin level and adverse events. RESULTS: Of the 62 patients on the study,
      there were 34(55%) patents in the Transaminegroup with a mean age of 64+/-8.4
      years, and28(45%)in the control group with a mean age of 60.8+/-10.3. The two
      groups were matched for demographic and blood indices.Mean blood loss via intra
      articular drain in the control group was 619+/-243ml per knee, and 402+/-169ml
      per knee in the Transaminegroup. Blood transfusions were required by
      14(50%)patients in the control groupand 6(17.6%)in the Transaminegroup.
      CONCLUSIONS: Perioperative intravenous transamine significantly reduced blood
      loss as well as blood transfusion requirements.

PMID- 25989781
TI  - Improvised explosive device bombing police bus: Pattern of injuries, patho
      physiology and early management.
AB  - OBJECTIVE: To understand the different types of blast injuries, their mechanisms,
      patho-physiology of wounds and clinical consequences caused by improvised
      explosive device detonation, and their early management. METHODS: The
      retrospective study related to 70 Special Security Unit personnel of police
      travelling on duty in a bus that was struck with an Improvised Explosive Device
      on February 13, 2014, at 7:48am.The data of triage, primary survey and
      resuscitation and secondary survey on arrival at the Accident and Emergency
      section of Jinnah Postgraduate Medical Centre, Karachi, were noted and later
      analysed. RESULTS: Police commandos aged 20-32 years were brought to hospital
      within 35-55 minutes of blast by ambulances. Triage at Emergency labelled
      11(15.7%) Black, 15(21.4%) Red, 19(27.2%) Yellow and 25(35.7%) Green. Primary
      blast waves led to 11 closed blast lung presenting as pneumothorax in 9(12.8%)
      patients; 11(15.7%) chest tube thoracotomies were performed. Primary blast waves
      also produced ear drum and eyeball perforation. Seven (10%) patients received
      calcaneal fractures; 2(2.8%) with bilateral calcaneal fractures. Tertiary blast
      waves also caused amputations, and lower leg open fractures. Patients who died
      had received multi-system involvement injuries due to combined primary and
      secondary blast waves. CONCLUSIONS: Improvised explosive devices produce a
      variety of serious and uncommon injuries requiring special care and early multi
      disciplinary response. Repeated primary and secondary survey in Accident and
      Emergency are very important.

PMID- 25989782
TI  - Metallosis, complete osteolysis of ilium, acetabulum and proximal femur.
      Disastrous complication of total hip arthoplasty: A case report.
AB  - Metallosis is serious condition that comes about when metallic debris builds up
      in the soft tissues of the body. This condition is seen in individuals undergoing
      joint replacement surgery, like those of the hip, knee and elbow. Incidence of
      metallosis is not common. Here we present a case of 61 year-old male, who had
      undergone right-sided total hip replacement 20 years earlier due to avascular
      necrosis. He presented to us with one-year history of massive swelling of right
      thigh and mild pain and discomfort in September 2013. He was unable to carry
      weight on the affected limb and had been bed-ridden for the preceding three
      months. On surgery, we found that the femur had eroded on the medial side, and
      the whole illium had been destroyed except the iliac crest. We removed the stem,
      some metal particles and the fibrous tissue. After 2 months of surgery, he died
      of myocardial infarction. 

PMID- 25989783
TI  - "The role and ability of orthopaedic postgraduate resident's clubfoot treatment
      with ponseti's methodology." A comparative study of resident's versus
      consultant's directed treatment.
AB  - OBJECTIVE: To evaluate the outcome of Ponseti treatment carried out by the
      Postgraduate Orthopaedic Trainees compared with the treatment given by their
      Mentors. METHODS: The prospective comparative case series study was conducted at
      Jinnah Postgraduate Medical Centre, Karachi, and comprised idiopathic Congenital
      Clubfoot Deformity patients treated from September 2012 to December 2013. Also
      included were a few cases treated between September 2006 and September 2012, who
      had complete record, serial photograph and updated follow-up. The patients were
      divided into two groups. Those treated by residents formed Group A and those by
      consultants were in Group B. The follow-up duration ranged from 06 months to 05
      years. Outcome measures included the number of casts required to achieve
      correction with Pirani score 0.5, the rate of Per-Cutaneous Achilles Tenotomy
      (PCAT), the rate of early relapse and treatment and failure to maintain
      correction. SPSS 13 was used for statistical analysis. RESULTS: Of the 172
      patients in the study, 111(64.5%) patients with 185 feet were treated by the
      residents, while 61(35.5%) patients with 96 feet were treated by consultant. The
      overall mean age was 25.8+/-32.88 weeks (range: 1-156 weeks). The difference in
      age between the two groups was significant (p=0.01). A total of 166(96.51%)
      patients were on maintenance phase in Foot Abduction Bracing and 6(3.48%)
      completed the treatment successfully without residual deformity. The median
      number of cast per patient given by Group A was 6 and 5 in Group B. The number of
      8+ casts given in Group A were 46 (24.86%) and 17 (17.7%) in Group B. Tenotomies
      performed in Group A were 106 (57.27%) and 70 (73%) in Group B, and overall PCAT
      performed were 183 (65.12%). The overall success rate was nearly similar between
      the two groups, with the difference of<1%. CONCLUSIONS: The best practice to
      achieve excellent to good results from the beginners in Ponseti technique is to
      provide mentorship training for the skill of Ponseti manipulation, application of
      cast and continued treatment.

PMID- 25989784
TI  - Treatment of long-segment fracture at middle-up part of femur with long proximal
      femoral nail antirotation.
AB  - OBJECTIVE: To investigate the results of non-invasive operation method and
      evaluate clinical and radiological outcome of long proximal femoral nail
      antirotation in treating long-segment fracture at middle-up part of femur.
      METHODS: The retrospective study was conducted at the Second Hospital of Fuzhou,
      China, and comprised cases of long-segment fracture in middle-up part of femur
      power treated with long proximal femoral nail antirotation between June 2006 and
      December 2013. The patients were followed up for a minimum of 9 months. Clinical
      outcomes were evaluated according to Harris Hip Score and radiological
      examinations were done at 1, 2, 3, 6, 9 and 12 months and once a year thereafter.
      RESULTS: Of the 139 patients, 104(75%) were males and 35(25%) females, within the
      age range of 18-86 years. The time period from injury to the index ranged from 3h
      to 15 days. The operative time of all cases ranged from 35 to 90 minutes, while
      the blood loss during surgery ranged from 30ml to 200ml. All patients walked with
      walking aid appliance 4-10 days post-operation with partial and gradually
      increasing to full weight-bearing. None of the patients developed infection,
      thrombus, cut-out or breakage of the implants. Follow-ups ranged from 9 to 37
      months. According to Harris Hip Functional Score, 108(77.7%) cases behaved
      excellent, 22(15.9%) good, 8(5.7%) fair, and 1(0.7%) case poor. The good rate, as
      such, was 130(93.5%). CONCLUSIONS: Long proximal femoral nail antirotation is an
      effective treatment method for long-segment fracture at middle upper part of
      femur, with high healing rate, quick function recovery as well as less
      complication incidence.

PMID- 25989785
TI  - Difficulties in maintenance of clubfoot abduction brace and solutions -
      maintenance of clubfoot abduction brace, locks and keys.
AB  - OBJECTIVE: To determine the frequency of early relapse after achieving good
      initial correction in children who were on clubfoot abduction brace. METHODS: The
      cross-sectional study was conducted at the Jinnah Postgraduate Medical Centre,
      Karachi, and included parents of children of either gender in the age range of 6
      months to 3years with idiopathic clubfoot deformities who had undergone Ponseti
      treatment between September 2012 and June 2013, and who were on maintenance brace
      when the data was collected from December 2013 to March 2014. Parents of patients
      with follow-up duration in brace less than six months and those with syndromic
      clubfoot deformity were excluded. The interviews were taken through a purposive
      designed questionnaire. SPSS 16 was used for data analysis. RESULTS: The study
      included parents of 120 patients. Of them, 95(79.2%) behaved with good compliance
      on Denis Browne Splint, 10(8.3%) were fair and 15(12.5%)showed poor compliance.
      Major reason for poor and non-compliance was unaffordability of time and cost for
      regular follow-up. Besides, 20(16.67%) had inconsistent use due to delay inre
      procurement of Foot Abduction Braceonce the child had outgrown the shoe. Only
      4(3.33%) talked of cultural barriers and conflict of interest between the
      parents. Early relapse was observed in 23(19.16%) patients and 6(5%) of them
      responded to additional treatment and were put back on brace treatment;
      13(10.83%) had minor relapse with forefoot varus, without functional disability,
      and the remaining 4(3.33%) had major relapse requiring extensive surgery. Overall
      success was recorded in 116(96.67%) cases. CONCLUSIONS: The positioning of shoes
      on abduction brace bar, comfort in shoes, affordability, initial and subsequent
      delay in procurement of new shoes once the child's feet overgrew the shoe, were
      the four containable factors on the part of Ponseti practitioner.

PMID- 25989786
TI  - Precontoured anatomical plates new era in the complex tibail plateau fractures
      fixation.
AB  - OBJECTIVE: Functional outcome of Intraarticular Tibial Plateau Fractures fixed
      with precontoured anatomical plates using Knee Society Score. METHODS:
      Observational study with retrospective review of collected data. Patient's
      demography, mechanism of injury, schatzker's classification includingtype IV, V
      and VI. All patients underwent screw and plate fixation using two incision
      technique with pre-contoured anatomical plates and intercondylar lag screws where
      indicated. Passive range of motion exercises started at 2 weeks. Postoperative
      knee pain, range of motion and stiffness were recorded at followup 3 and 4
      months. Mean+/-SD were calculated for quantitative variables and qualitative
      variables were presented with frequency and percentages. The association of
      outcome (Knee Society Score) with gender, age and Schatzker's type was evaluated
      by applying Fisher's Exact test considering p-value <0.05 as significant.
      RESULTS: Twenty-five patients were included in study. 20 patients were available
      and 05 lost to follow up. 16 were males and 4 females out of 20 patients. Average
      age is 36.2+/-12.89 years. All patients sustained injuries after RTA. 5 patients
      had postoperative knee pain while remaining were pain free. Average flexion was
      123.8 with (SD 8.88)range of 105 to 135 degree. Average extension was 3.15 with
      (SD 2.41) range of 0 to 8 degress. 4 patients developed stiffness of knee. 2
      patients symptomatic implant. All fractures healed at follow up at 4 months.
      According to Knee Society score (SD 7.65) 14 cases scored as good, 4 cases scored
      fair and 2 cases scored poor. There was no association of knee score was found
      with gender (p=0.493) but significant association of knee score was found with
      age (p=0.007) and Schatzker's type (p=0.028). CONCLUSIONS: Tibial plateau
      fractures can be effectively treated by anatomical reduction and absolute
      fixation using pre-contoured anatomical plates. Functional outcome calculated by
      Knee Society score is better in young patients. With appropriate surgical
      techniques and early post-operative rehabilitation, good functional results can
      be achieved.

PMID- 25989787
TI  - Functional outcome of ACL reconstruction using patellar bone tendon bone graft.
AB  - PURPOSE: To evaluate the mid-term functional outcome using Lysholm score of
      anterior cruciate ligamentreconstruction using bone patella-tendon bone graft.
      METHODS: The retrospective study of prospectively collected data was conducted at
      Liaquat National Hospital, Karachi, from June 2010to June 2013, and comprised
      patients with complete anterior cruciate ligamenttear who were treated with
      diagnostic arthroscopy and open reconstruction using bone patella-tendon bone
      graft. All patients were operated under tourniquet control and knee immobiliser
      was applied. Straight leg raise procedure was started on 2nd postoperative day.
      One year after surgery, functional outcome was assessed using Lysholm score.
      RESULTS: All the 36(100%) patients in the study were males. Four (11%) patients
      were lost to follow-up and were excluded, while 32(89%) completed the study.
      Right knee was involved in 16(50%) patients while left knee was involved in
      16(50%) patients. Overall, 31(97%) patients had history of contact sports injury.
      The average age of patients was 28.25+/-8.32 years. All patients were operated at
      an average of 17.5+/-10.3 weeks. The ligament tear was associated with medial
      meniscal tear in 16(50%) patients, while lateral meniscal tear was noted in
      10(31.25%). The mean Lysholm score was 83.06+/-4.17at 1 year (fair to good
      outcome). The average range of motion 1 year after surgery was 127.5+/-11.25.
      Loss of extension <3o was noted in 20(62.5%) patients, while >3o was noted in
      12(37.5%). The average loss of extension was 3.5+/-2.3 degrees. Two (6.25%)
      patients developed superficial infection which subsided with oral antibiotics.
      Anterior knee pain was reported by 8(25%) patients. CONCLUSIONS: Patellar bone
      tendon bone graft was a reliable method for reconstruction of anterior cruciate
      ligament.

PMID- 25989788
TI  - Anthropomorphic mismatch between distal femurs and a standard total knee
      replacement system in Pakistani population.
AB  - AIMS: To compare the measurements of distal femurs of a Pakistani population and
      with the implants used. METHODS: The single-centre prospective cross-sectional
      study was conducted at the Indus Hospital, Karachi, from 01-06-2011 to 31-10
      2011, and comprised total knee replacement patients. Surgeries were performed by
      the same team. Each measurement was taken after the resection of the trochlea
      (flush to the anterior femoral cortex), the distal cut and the anterior chamfer
      cuts. Measurements were taken intraoperatively with a sterile vernier calliper.
      SPSS 17was used to analyse the data. RESULTS: The mean age of the 33 patients in
      the study was 59.3+/-7years. There were 4(12.1%) males and 29(87.9%) females. A
      mismatch was found in per-operative measurements with the mean aspect ratio being
      0.79+/-0.05and the standardised aspect ratio of the implants being 0.90 (SD+/
      0.0). CONCLUSIONS: There are differences between anthropomorphometry of our
      skeleton and Caucasian designed implants. This could have implications in the
      long term.

PMID- 25989789
TI  - Early outcome of surgical intervention in subaxial cervical spine injuries.
AB  - OBJECTIVE: To determine the surgical outcome of patients with axial cervical
      spine fractures. METHODS: The study was conducted at the Spine Unit of Hayatabad
      Medical Complex, Peshawar, and Aman Hospital, Peshawar, from January 2012 to
      March 2013. Patients with sub-axial cervical spine fractures were treated
      surgically. The outcome was measured using Visual Analogue Score, Neck Disability
      Index, by neurology and on the basis of complications. SPSS 16 was used for
      statistical analysis. RESULTS: Of the 50 patients in the study, 7(14%) were
      females, while 43(86%) were male. Overall mean age was 30.3+/-7.9 years (range:
      18-60 years). Major cause of injury was road traffic accidents in 29(58%). A
      total of 29(58%) patients had dislocation of the spine which was successfully
      reduced in 22(75.9%). Mean postoperative visual analogue score was 2.9+/-1.5
      (range: 1-7) at last follow-up. Mean neck disability index score was 10.9+/-5.2
      (range: 4-26). Dysphagia was the most common complication in 12(24%).
      CONCLUSIONS: Majority of the sub-axial fractures can be treated effectively with
      good outcome through anterior approach. Gradual axial skull traction is an easy
      and safe method for reduction of cervical fracture dislocations.

PMID- 25989790
TI  - The use of locally harvested bone chips as a graft in spine fusion surgery.
AB  - OBJECTIVE: To evaluate the outcome of local corticocancellous bone chips used for
      fusion in various kinds of spine surgeries. METHODS: The observational
      prospective study was conducted at the Hayatabad Medical Complex, Peshawar, and
      Aman Hospital, Peshawar, from April 2011 to April 2013, and comprised cases in
      which locally harvested bone chips removed during decompression were used as bone
      graft for arthodesis. All cases were successfully followed up for at least one
      year. SPSS 16 was used for statistical analysis. RESULTS: Of the80 patients in
      the study, 44(55%) were female and 36(45%) were male. The overall mean age was
      39.5+/-12.7 years (range: 13-75 years). Besides, 34(42.5%) were operated for
      spine surgery, 22(27.5%) for spondylolisthesis, 12(15.0%) for disc degeneration
      and 12 (15%) for spinal stenosis. In 54(67.5%) patients posterio-lateral fusion
      with decompression was done, while in 26(32.5%) transforaminal lumbar interbody
      fusion was done. Oswestry Disability Index scoreat last follow-up ranged from 4
      to 56 with a mean of 17.7+/-10.7. CONCLUSIONS: Locally harvested bone chips are
      reasonable alternative to iliac crest bone graft, having comparable results while
      avoiding donor site morbidity associated with iliac crest bone grafts.

PMID- 25989791
TI  - Knee dislocations and popliteal artery injury: A single centre experience from
      Karachi.
AB  - OBJECTIVE: To determine the association of popliteal artery injury with simple
      knee dislocations or knee fracture dislocations, and to evaluate the role of
      clinical assessment and colour Doppler ultrasound examination in diagnosing these
      injuries. METHODS: The prospective case series study was done at the Liaquat
      National Hospital, Karachi, and comprised patients with simple knee dislocations
      or knee fracture dislocations presenting between February 2013 and April 2014.
      All patients underwent clinical assessment including distal pulse examination and
      signs of vascular trauma. Following reduction of dislocation, repeat clinical
      examination and assessment of limb with colour Doppler ultrasound was carried
      out. RESULTS: Out of 9 patients in the study, 6(66.7%)had simple dislocations,
      while 3(33.3%) sustained fracture dislocations of the knee. Two (22%) patients
      sustained injury to the popliteal artery which was effectively managed via
      surgical treatment. Clinical examination of the affected extremities effortlessly
      revealed the 2(22%) vascular trauma cases. Doppler ultrasound was carried out in
      8(89%) cases and it successfully excluded 7(78%) cases for vascular trauma and
      identified 1(11%) injury with reduced flow. This case underwent computed
      angiography scan and later surgery revealed popliteal artery trauma. Doppler
      ultrasound was not carried out in 1(11%) case which was a spontaneously relocated
      knee with hard signs of vascular injury. CONCLUSIONS: Popliteal artery injury can
      be a limb-threatening complication following trauma to the knee. Carefully
      performed clinical examination and colour Doppler ultrasound are effective tools
      for identification of such cases.

PMID- 25989793
TI  - Editorial.

PMID- 25989792
TI  - Dynamic hip screw fixation for inter-trochanteric fractures: determinants of
      outcomes.
AB  - OBJECTIVE: To evaluate factors associated with revision of dynamic hip screw
      implant in patients undergoing the procedure for the fixation of
      intertrochanteric fractures. METHODS: The retrospective study was conducted at
      the Aga Khan University Hospital, Karachi, and comprised records of patients who
      had undergone dynamic hip screw fixation surgery between 2008 and 2012. Medical
      records and data for all patients were obtained from the medical records office.
      For all patients, the record files were systematically reviewed using a
      structured, pre-defined data extraction sheet. SPSS 20 was used statistical
      analysis. RESULTS: Out of 317 patients who had undergone the procedure, 8(2.5%)
      were excluded due to missing records. The study sample as such stood at
      309(97.5%). Of them, 6(1.9%) required revision of the dynamic hip screw placed
      initially. High tip apex distance was found to be associated with the revision
      (p<0.0001).Demographic parameters and co-morbid conditions were not associated
      with a need for revision surgery (p>0.05). CONCLUSIONS: Patients requiring
      dynamic hip screw implant revision had higher tip apex distance than the rest. A
      lower value is advisable during placement of the screw to reduce the need for
      subsequent revision.

PMID- 25989794
TI  - T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell
      proliferation and induce cell apoptosis in leukemia cell lines.
AB  - BACKGROUND: T-type Ca(2+) channels are often aberrantly expressed in different
      human cancers and participate in the regulation of cell cycle progression,
      proliferation and death. METHODS: RT-PCR, Q-PCR, western blotting and whole-cell
      patch-clamp recording were employed to assess the expression of T-type Ca(2+)
      channels in leukemia cell lines. The function of T-type Ca(2+) channels in
      leukemia cell growth and the possible mechanism of the effect of T-type Ca(2+)
      channel antagonists on cell proliferation and apoptosis were examined in T
      lymphoma cell lines. RESULTS: We show that leukemia cell lines exhibited reduced
      cell growth when treated with T-type Ca(2+) channel inhibitors, mibefradil and
      NNC-55-0396 in a concentration-dependent manner. Mechanistically, these
      inhibitors played a dual role on cell viability: (i) blunting proliferation,
      through a halt in the progression to the G1-S phase; and (ii) promoting cell
      apoptosis, partially dependent on the endoplasmic reticulum Ca(2+) release. In
      addition, we observed a reduced phosphorylation of ERK1/2 in MOLT-4 cells in
      response to mibefradil and NNC-55-0396 treatment. CONCLUSIONS: These results
      indicate that mibefradil and NNC-55-0396 regulate proliferation and apoptosis in
      T-type Ca(2+) channel expressing leukemia cell lines and suggest a potential
      therapeutic target for leukemia.

PMID- 25989796
TI  - Poorly controlled cholesterol is associated with cognitive impairment in T2DM: a
      resting-state fMRI study.
AB  - BACKGROUND: Debate remains on whether hypercholesterolemia is associated with
      cognitive impairment. Hence, we investigated whether poorly controlled
      cholesterol impairs functional connectivity among patients with type 2 diabetes
      mellitus (T2DM). METHODS: Resting-state functional connectivity infers to an
      interregional cooperation characterized by synchronous and low-frequency (<0.08
      Hz) fluctuations on blood oxygen level-dependent functional magnetic resonance
      imaging (fMRI). We used resting-state fMRI to investigate the functional
      connectivity of 25 T2DM patients with poorly controlled cholesterol, 22 patients
      with target cholesterol and 26 healthy controls. Further correlation analysis was
      conducted between the functional connectivity and clinical data as well as
      neuropsychological tests. RESULTS: The three groups did not statistically differ
      in age, sex, education level, body mass index, blood pressure, fasting C
      peptides, and triglyceride. Compared with target cholesterol patients, patients
      with poorly controlled cholesterol showed significantly increased levels of serum
      cholesterol, low-density lipoprotein (LDL), and LDL/high-density lipoproteins
      (HDL) ratio, as well as poor performance in Trail Making Test B (TMT-B) (p<0.05).
      Disordered functional connectivity of bilateral hippocampus-middle frontal gyrus
      (MFG) in the poorly controlled group consistently existed when compared with the
      two other groups. Moreover, the aberrant functional connectivity was associated
      with the TMT-B scores and the LDL/HDL index in T2DM patients with poorly
      controlled cholesterol. CONCLUSIONS: T2DM patients with poorly controlled
      cholesterol showed impaired attention and executive function. The resting-state
      connectivity disturbance of the hippocampus-MFG may be involved in this process.
      Decreasing the LDL/HDL ratio can be taken as precaution against cognitive
      decrements.

PMID- 25989795
TI  - The origin of snakes: revealing the ecology, behavior, and evolutionary history
      of early snakes using genomics, phenomics, and the fossil record.
AB  - BACKGROUND: The highly derived morphology and astounding diversity of snakes has
      long inspired debate regarding the ecological and evolutionary origin of both the
      snake total-group (Pan-Serpentes) and crown snakes (Serpentes). Although
      speculation abounds on the ecology, behavior, and provenance of the earliest
      snakes, a rigorous, clade-wide analysis of snake origins has yet to be attempted,
      in part due to a dearth of adequate paleontological data on early stem snakes.
      Here, we present the first comprehensive analytical reconstruction of the
      ancestor of crown snakes and the ancestor of the snake total-group, as inferred
      using multiple methods of ancestral state reconstruction. We use a combined-data
      approach that includes new information from the fossil record on extinct crown
      snakes, new data on the anatomy of the stem snakes Najash rionegrina, Dinilysia
      patagonica, and Coniophis precedens, and a deeper understanding of the
      distribution of phenotypic apomorphies among the major clades of fossil and
      Recent snakes. Additionally, we infer time-calibrated phylogenies using both new
      'tip-dating' and traditional node-based approaches, providing new insights on
      temporal patterns in the early evolutionary history of snakes. RESULTS:
      Comprehensive ancestral state reconstructions reveal that both the ancestor of
      crown snakes and the ancestor of total-group snakes were nocturnal, widely
      foraging, non-constricting stealth hunters. They likely consumed soft-bodied
      vertebrate and invertebrate prey that was subequal to head size, and occupied
      terrestrial settings in warm, well-watered, and well-vegetated environments. The
      snake total-group - approximated by the Coniophis node - is inferred to have
      originated on land during the middle Early Cretaceous (~128.5 Ma), with the crown
      group following about 20 million years later, during the Albian stage. Our
      inferred divergence dates provide strong evidence for a major radiation of
      henophidian snake diversity in the wake of the Cretaceous-Paleogene (K-Pg) mass
      extinction, clarifying the pattern and timing of the extant snake radiation.
      Although the snake crown-group most likely arose on the supercontinent of
      Gondwana, our results suggest the possibility that the snake total-group
      originated on Laurasia. CONCLUSIONS: Our study provides new insights into when,
      where, and how snakes originated, and presents the most complete picture of the
      early evolution of snakes to date. More broadly, we demonstrate the striking
      influence of including fossils and phenotypic data in combined analyses aimed at
      both phylogenetic topology inference and ancestral state reconstruction.

PMID- 25989798
TI  - Aspects of the Health Inspection Authority in the People's Republic of China.
AB  - BACKGROUND: In China, there was a pressing need to establish a governmental
      agency to oversee the organizations that provide public health and medical
      services. The Chinese Health Inspection Authority (HIA), a relatively independent
      organization functioning at each administrative level (provincial, municipal, and
      county), was mandated to conduct 11 health inspection functions to maintain
      efficient public health and medical services. These functions include issuing
      health permit, conducting health supervision and inspection, health testing and
      evaluation, case investigation, complaint handling, managing public health
      crisis, monitoring and safeguarding public health at major public events,
      enforcing supervision and inspection compliance, public health education,
      information management, and team training and management. Since the reform of the
      health inspection system by the Ministry of Health in 2000, the HIA underwent a
      series of changes and transitions. This study aimed to describe and assess the
      five factors that were considered to be important for meeting service delivery
      objectives of the HIA in the People's Republic of China. METHODS: A total of 604
      HIAs, sampled across three geographical regions of China at three administrative
      levels, participated in a cross-sectional survey conducted in 2013. Descriptive
      statistics were used to analyze the status of mandated operations, manpower,
      revenue and expenditures, and institutional infrastructure. Differences in these
      characteristics across the geographical regions and administrative levels were
      compared. RESULTS: On average, the HIAs had not fully implemented the 11 mandated
      functions at any administrative levels. Governmental financial allocations were
      the main sources of revenue. Three primary personnel employment models coexisted
      and most employed the quasi-civil service employment model. The institutional
      infrastructure did not meet governmental mandated standards with respect to
      building area or the number and types of equipment available to conduct key
      functions. CONCLUSIONS: In 2012, the majority of the HIAs in China at the
      provincial, municipal, and county levels did not meet the mandated requirements,
      although positive indications toward meeting these requirements were observed. It
      is necessary for the government to pay more attention to institutional resources
      (buildings, equipment, and the level of the staff's educational attainment) and
      ensure that the HIAs can meet their service delivery objectives.

PMID- 25989797
TI  - Low birth weight and prenatal care in Colombia: a cross-sectional study.
AB  - BACKGROUND: Low birth weight (LBW) is one of the most important factors affecting
      child morbidity and mortality worldwide; approximately one third of neonatal
      deaths are attributable to it. Most research and public health policy on LBW
      arise from developed nations, despite that most cases (96.5%) take place in
      developing countries. The specific features of prenatal care that prevent LBW in
      developing countries are unclear. This study aims to identify the characteristics
      of prenatal care associated with LBW in a developing country as Colombia.
      METHODS: Observational cross-sectional study using data from the Colombian
      Demographic and Health Survey 2010. A total of 10,692 children were included.
      Descriptive statistics were calculated, followed by bivariate regressions of LBW
      with all other study variables. Finally, stepwise logistic binomial regression
      analyses were done. RESULTS: A LBW prevalence of 8.7% was found. Quality of
      prenatal care (95%CI: 0.33, 0.92; OR = 0.55), number of prenatal visits (95%CI:
      0.92, 0.93; OR = 0.92), and first prenatal visits during pregnancy (95%CI: 1.02,
      1.07; OR = 1.08) were associated with LBW even after controlling for all the
      studied variables. The health care provider conducting prenatal checkup, and
      insurance coverage, were not associated with LBW. CONCLUSION: This research
      provides information on the characteristics of prenatal care (quality, number of
      visits, and gestational age at first prenatal visit) which may strengthen LBW
      prevention in Colombia and possibly in countries with similar socioeconomic
      characteristics.

PMID- 25989799
TI  - Withaferin A Regulates LRRK2 Levels by Interfering with the Hsp90- Cdc37
      Chaperone Complex.
AB  - Leucine-Rich Repeat Kinase 2 (LRRK2) is a large, multi-domain protein that has
      been found to be mutated in patients with familial and sporadic Parkinson's
      disease, Alzheimer's disease and Crohn's disease. While the functions of LRRK2
      are still largely unclear and mutations in LRRK2 are associated with adverse gain
      of-function activities such as increased kinase activity, increased levels of
      LRRK2 alone are associated with toxicity in neurons. Consequently, exploring
      mechanisms to decrease levels of LRRK2 using pharmacological inhibitors would be
      highly advantageous. Previous work has shown that the chaperone heat shock
      protein 90 (Hsp90) and its co-chaperone Cdc37 interact with and stabilize LRRK2.
      In the current study, we explore the regulation of LRRK2 by withaferin A (WA), a
      potent inhibitor of the interaction between Hsp90 and Cdc37. We report that
      treatment of the microglial cell line N9 with WA causes a decrease in cellular
      levels of LRRK2 in a dose- and time-dependent manner. We also find that treatment
      with WA disrupts the interaction between Hsp90, its co-chaperone Cdc37 and LRRK2,
      which leads to the destabilization and decreased levels of LRRK2. Additionally,
      treatment with celastrol, which is also an inhibitor of the Hsp90-Cdc37 complex,
      decreased LRRK2 levels. Interestingly, treatment with WA in the presence of
      celastrol enhanced the clearance of LRRK2. Overall, our data suggest that LRRK2
      levels can be regulated by targeting the Hsp90-Cdc37 complex, which may have
      implications in the search for therapeutic strategies for Alzheimer's disease,
      Parkinson's disease and other LRRK2 proteinopathies. 

PMID- 25989800
TI  - Comparison of Arthroscopic Microfracture for Osteochondral Lesions of the Talus
      With and Without Subchondral Cyst.
AB  - BACKGROUND: Although various treatment modalities for an osteochondral lesion of
      the talus (OLT) with a subchondral cyst have been recommended previously, the
      primary treatment methods for such conditions have yet to be conclusively
      determined. Moreover, few comprehensive studies have compared the outcomes of
      cases where patients were treated with microfracture for OLT with and without
      subchondral cysts. PURPOSE: To evaluate the clinical outcomes after arthroscopic
      microfractures performed as a primary treatment for OLT with a subchondral cyst.
      STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The study cohort
      consisted of 102 patients (102 ankles) who underwent arthroscopic microfracture
      for small to midsized OLT. The ankles were divided into a cyst group (45 ankles)
      and a noncyst group (57 ankles).The American Orthopaedic Foot and Ankle Society
      (AOFAS) ankle-hindfoot scale, visual analog scale (VAS), and Ankle Activity Score
      (AAS) were used to compare the clinical outcomes between the groups over a mean
      follow-up period of 48 months. RESULTS: The mean AOFAS ankle-hindfoot scores were
      64.8 in the cyst group and 66.2 in the noncyst group preoperatively. These
      improved to 91.8 and 91.3, respectively, at the final follow-up. The mean VAS
      scores were 7.5 in the cyst group and 7.3 in the noncyst group preoperatively;
      these improved to 2.3 and 2.2, respectively, at the final follow-up. The mean AAS
      in the cyst group and the noncyst group improved from 2.7 and 2.6 preoperatively
      to 6.7 and 6.5 at the final follow-up, respectively. In terms of radiographic
      stage improvements, the cyst group showed no change in 18 ankles (40%) and showed
      improvements of 1 grade in 13 ankles (28.9%), 2 grades in 9 ankles (20%), 3
      grades in 3 ankles (6.7%), and 4 grades in 2 ankles (4.4%). The noncyst group
      showed no change in 17 ankles (29.8%) and showed improvements of 1 grade in 11
      ankles (19.3%), 2 grades in 11 ankles (19.3%), 3 grades in 14 ankles (24.6%), and
      4 grades in 4 ankles (7.0%). No significant differences were found between the
      groups in terms of the AOFAS score, VAS score, AAS, or radiographic stage
      improvements. CONCLUSION: OLT with and without subchondral cysts treated with
      arthroscopic microfracture showed similarly good clinical results. The study
      results suggest that microfracture could be a primary treatment strategy for
      treating small to midsized OLT regardless of the existence of subchondral cysts.

PMID- 25989801
TI  - Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic
      Review.
AB  - Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends
      survival in patients with advanced biliary tract cancer (BTC). We conducted a
      systematic review in order to collate this evidence and assess whether
      gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease
      stage, or geographic region, and whether associated toxicities are related to
      regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials.
      gov (2008-search date), and abstracts from major oncology conferences (2009-
      search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and
      cisplatin. All study types reporting efficacy (survival, response rates) or
      safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for
      inclusion; efficacy data were extracted from prospective studies only. Evidence
      retrieved from one meta-analysis (abstract), four randomized controlled trials,
      12 nonrandomized prospective studies, and three retrospective studies supported
      the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival
      ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%.
      Toxicities were generally acceptable and manageable. Heterogeneity in study
      designs and data collected prevented formal meta-analysis, however exploratory
      assessments suggested that efficacy did not vary with primary tumor site
      (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or
      geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not
      related to gemcitabine dose or cisplatin frequency. Despite individual variation
      in study designs, the evidence presented suggests that gemcitabine-cisplatin is
      effective in patients from a diverse range of countries and with heterogeneous
      disease characteristics. No substantial differences in toxicity were observed
      among the different dosing schedules of gemcitabine and cisplatin. 

PMID- 25989802
TI  - The Prognostic Significance of FGFR4 Gly388 Polymorphism in Esophageal Squamous
      Cell Carcinoma after Concurrent Chemoradiotherapy.
AB  - PURPOSE: The purpose of this study is to investigate the role of fibroblast
      growth factor receptor 4 (FGFR4) polymorphism in esophageal cancer after
      chemoradiotherapy (CRT). MATERIALS AND METHODS: Peripheral blood samples from 244
      patients treated with CRT for esophageal squamous cell carcinoma were assessed
      for the role of FGFR4 genotype on treatment response and survival. RESULTS: A
      total of 94 patients were homozygous for the Gly388 allele, and 110 were
      heterozygous and 40 homozygous for the Arg388 allele. No significant association
      was found between the FGFR4 genotype and clinicopathological parameters. However,
      patients carrying the Gly388 allele showed a better overall response rate than
      Arg388 carriers (p=0.038). In addition, Gly388 allele patients at an earlier
      stage showed better overall survival (OS) and progression-free survival than
      Arg388 carriers. Among these, the Gly388 allele showed significantly improved OS
      compared to Arg388 carriers in the lymph node (LN) metastasis group (p=0.042)
      compared to the no LN metastasis group (p=0.125). However, similar survival
      outcomes were observed for advanced-stage disease regardless of genotype.
      CONCLUSION: This result suggests that the role of FGFR4 Gly388 in treatment
      outcomes differs according to esophageal cancer stage. It showed a predictive
      role in the response of esophageal cancer patients to CRT with a better trend for
      OS in Gly388 than Arg388 carriers in the early stages. In particular, LN-positive
      early-stage patients carrying the Gly388 allele showed improved OS compared to
      those carrying Arg388.

PMID- 25989804
TI  - Exploring perceptions and use of the electronic health record by parents of
      children with autism spectrum disorder: A qualitative study.
AB  - This qualitative project used structured interviews with nine parents to examine
      perceptions of the electronic health record (EHR) and associated patient portal
      in the treatment of their child's autism spectrum disorder. Thematic analysis
      identified six complementary themes including: Familiarity and exposure to the
      EHR, changing experience of care (streamlining appointments, providing more rapid
      medical record access, increasing clinician awareness of the complexity of their
      child's medical treatment, and facilitating prescriptions), portal use,
      patient/EHR/portal interaction, interoperability, and mother as care coordinator.
      While aware of the patient portal, only one-third had registered to use it and
      these parents reported only limited use. In general, perceptions of the
      electronic health record are positive, but the patient portal has yet to have
      needed consumer adoption. Further research and functionality are needed to
      increase portal registration and greater portal integration in patient care.

PMID- 25989803
TI  - Age-Period-Cohort Analysis of Female Breast Cancer Mortality in Korea.
AB  - PURPOSE: Despite the low mortality rate of breast cancer among women in Korea,
      the breast cancer mortality rate has increased. The aim of this study was to
      examine trends in breast cancer mortality from 1983 to 2012 in Korea, assessing
      the importance of age, period, and birth cohort as risk factors. MATERIALS AND
      METHODS: Data on the annual number of deaths due to female breast cancer and on
      female population statistics from 1983 to 2012 were obtained from Statistics
      Korea. A log-linear Poisson age-period-cohort model was used to estimate age,
      period, and cohort effects. RESULTS: The increasing breast cancer mortality can
      be explained predominantly by a birth cohort effect: the risk of breast cancer
      death showed a steady increase until the 1968 birth cohort, and decreased
      thereafter. There was a sharp increase in the magnitude of the age effect up to
      60 years old, then a moderate increase in the effect during the sixties, followed
      by another sharp increase from 70 years old. The period effect on breast cancer
      mortality seems negligible based on its adjusted relative risk, even though it
      was statistically significant after adjusting for age and cohort effects.
      CONCLUSION: In this study, the mortality pattern of breast cancer in Korea can be
      explained predominantly by a birth cohort effect. Hence, the overall mortality
      rate of breast cancer may increase for a while, and show a gradual decrease in
      the future, which will start from the younger age group.

PMID- 25989806
TI  - The effects of decentralizing anti-retroviral services in Nigeria on costs and
      service utilization: two case studies.
AB  - Nigeria launched a 'hub and spoke' decentralization pilot in March 2010 for the
      provision of anti-retroviral therapy (ART). In this programme, stable ART
      patients at hospitals (hubs) were referred to primary health care centres
      (spokes) for the continued provision of ART. The objectives of this study are to
      compare the cost of ART care provided through the two levels of care. We also
      assess if decentralization was associated with changes in patients' service
      utilization. Data were collected from facilities and patient records from Kaduna
      and Cross Rivers States. Costs were collected from the provider perspective. In
      Cross River, 398 patients and 528 from Kaduna were included in the retrospective
      cohort. The analysis utilizes separate fixed effect regressions for each state to
      assess differences in costs and service utilization among patients that
      decentralized. Uptake of decentralized services was ~3% in Cross Rivers and ~9%
      in Kaduna among active ART patients in April 2011. Patients electing to
      decentralize had 40% (95% CI: 13% to 67%) higher costs in Cross Rivers and 29% (
      44% to -14%) lower costs in Kaduna as compared with patients that did not
      decentralize. Lower costs in Kaduna appear to result from shifting care to less
      expensive cadres of health workers (task shifting) rather than decentralization.
      Decentralization of health services is a complicated process and broad
      generalizations across settings and processes, concerning whether or not it
      reduces unit costs, are likely over-simplifications. Similarly, decentralization
      of ART services does not automatically increase access to ART care, and may limit
      access to ART laboratory services. This study is limited by not including costs
      incurred above the facility level, such as training, or costs borne by patients.

PMID- 25989805
TI  - Primary prevention with lipid lowering drugs and long term risk of vascular
      events in older people: population based cohort study.
AB  - OBJECTIVE: To determine the association between use of lipid lowering drugs
      (statin or fibrate) in older people with no known history of vascular events and
      long term risk of coronary heart disease and stroke DESIGN: Ongoing prospective
      population based cohort study recruited in 1999-2000, with five face-to-face
      examinations. SETTING: Random sample of community dwelling population aged 65
      years and over, living in three French cities (Bordeaux, Dijon, Montpellier).
      PARTICIPANTS: 7484 men and women (63%) with mean age 73.9 years and no known
      history of vascular events at entry. Mean follow-up was 9.1 years. MAIN OUTCOME
      MEASURES: Adjusted hazard ratios of coronary heart disease and stroke in baseline
      lipid lowering drug users compared with non-users, calculated using multivariable
      Cox proportional hazard models adjusted for numerous potential confounding
      factors. Hazard ratios were estimated for use of any lipid lowering drug and for
      statin and fibrate separately. RESULTS: Lipid lowering drug users were at
      decreased risk of stroke compared with non-users (hazard ratio 0.66, 95%
      confidence interval 0.49 to 0.90); hazard ratios for stroke were similar for
      statin (0.68, 0.45 to 1.01) and fibrate (0.66, 0.44 to 0.98). No association was
      found between lipid lowering drug use and coronary heart disease (hazard ratio
      1.12, 0.90 to 1.40). Analyses stratified by age, sex, body mass index,
      hypertension, systolic blood pressure, triglyceride concentrations, and
      propensity score did not show any effect modification by these variables, either
      for stroke or for coronary heart disease. CONCLUSION: In a population based
      cohort of older people with no history of vascular events, use of statins or
      fibrates was associated with a 30% decrease in the incidence of stroke.

PMID- 25989807
TI  - Influence of habitat and land use on the assemblages of ephemeroptera,
      plecoptera, and trichoptera in neotropical streams.
AB  - Insects of the orders Ephemeroptera, Plecoptera, and Trichoptera (EPT) are often
      used to assess the conditions of aquatic environments, but few studies have
      examined the differences in these communities between riffles and pools. Our
      objective was to test whether riffles shelter greater richness and abundance of
      EPT, as well as to assess the sensitivity of these insects for detecting impacts
      from different land uses in streams in southeastern Brazil. Samples were
      collected in the dry season of 2012 with a Surber sampler in riffles and pools of
      nine streams (forest, pasture, and urban areas). Principal component analysis
      distinguished the streams according to different land uses as a function of
      percentage of plant cover and water oxygenation level and showed partial
      distinction between riffles and pools as a function of current speed and
      percentage of ultrafine sand. Detrended correspondence analysis indicated the
      distinction in EPT composition between riffles and pools, except in urban
      streams. The results of this study confirm the expected differences in the EPT
      fauna structure between riffles and pools, especially in forest and pasture
      environments. The individual metrics of riffle and pool assemblages showed
      significantly different responses to land use. Therefore, we suggest individual
      sampling of riffles and pools, since the metrics of these assemblages' insects
      can differ between these habitats and influence the results of assessments in low
      order streams. 

PMID- 25989808
TI  - Monitoring Residual Platelet Activity Among Patients With Acute Coronary Syndrome
      Post-PCI by Modified Impedance Whole Blood Platelet Aggregation and Release
      Method.
AB  - Antiplatelet medicines have been one of the cornerstones in the treatment of
      patients with acute coronary syndrome (ACS). However, adverse cardiovascular
      events still occur in some patients on standard antiplatelet therapy. Therefore,
      a reliable laboratory test to monitor the residual platelet activity (RPA) is
      urgent. We aim to modify the impedance whole blood platelet aggregation (WBA)
      assay associated with release assay to monitor RPA, despite antiplatelet therapy
      and assess their relationship with clinical ischemic events. In this study, RPA
      was tested in 133 patients with ACS postpercutaneous coronary intervention
      between 24 and 36 hours after a 300-mg clopidogrel loading dose by modified
      assay. Then, these patients were followed up for 3 months for clinical ischemic
      events. Meanwhile, platelet activity of 58 healthy volunteers was also tested by
      modified assay. Results showed that in modified assay the point of platelet
      magnified activation time (MAT) and maximal platelet adenosine triphosphate
      release values (RV) have significant differences between healthy volunteers and
      patients ([90.86 +/- 27.60 seconds] vs [206.44 +/- 58.97 seconds] and [2.07 +/-
      0.64 nmol] vs [0.98 +/- 0.49 nmol];P< .001 andP< .001, respectively). During
      follow-up, 5 patients present ischemic events. Receiver-operator characteristic
      curve showed that the cutoff values for MAT and RV were 156.5 seconds and 1.05
      nmol, respectively, with the sensitivity and specificity of 60.00% and 83.30% and
      80.00% and 67.50%, respectively; when MAT combined with RV, the sensitivity can
      be increased to 100%. Therefore, modified impedance WBA and release assay may be
      a potentially recommended reliable laboratory assays for monitoring the RPA. 

PMID- 25989809
TI  - Complex tricuspid valve repair for infective endocarditis: leaflet augmentation,
      chordae and annular reconstruction.
AB  - Surgical treatment of tricuspid valve (TV) endocarditis remains a challenge
      because of extensive valve destruction, high risk of reinfection, poor outcomes
      with valve replacement and complex patient compliance issues. Reconstruction of
      the TV is certainly favoured over replacement; however, diffuse, multifocal
      vegetations and complete debridement often leave insufficient building materials
      necessary for repair. We describe our surgical reconstructive technique that
      relies upon extensive autologous pericardial patch augmentation of the destroyed
      TV leaflets to establish leaflet coaptation, supplemented with expanded
      polytetrafluoroethylene neo-chordae and annular reconstruction. We report our
      outcomes in a series of patients with grossly infected TVs with more than 50% of
      valvular destruction. 

PMID- 25989810
TI  - The Effect of Evolving Fluid Resuscitation on the Outcome of Severely Injured
      Patients: An 8-year Experience at a Tertiary Trauma Center.
AB  - BACKGROUND AND AIMS: Fluid resuscitation of severely injured patients has shifted
      over the last decade toward less crystalloids and more blood products. Helsinki
      University trauma center implemented the massive transfusion protocol in the end
      of 2009. The aim of the study was to review the changes in fluid resuscitation
      and its influence on outcome of severely injured patients with hemodynamic
      compromise treated at the single tertiary trauma center. MATERIAL AND METHODS:
      Data on severely injured patients (New Injury Severity Score > 15) from Helsinki
      University Hospital trauma center's trauma registry was reviewed over 2006-2013.
      The isolated head-injury patients, patients without hemodynamic compromise on
      admission (systolic blood pressure > 90 or base excess > -5.0), and those
      transferred in from another hospital were excluded. The primary outcome measure
      was 30-day in-hospital mortality. The study period was divided into three phases:
      2006-2008 (pre-protocol, 146 patients), 2009-2010 (the implementation of massive
      transfusion protocol, 85 patients), and 2011-2013 (post massive transfusion
      protocol, 121 patients). Expected mortality was calculated using the Revised
      Injury Severity Classification score II. The Standardized Mortality Ratio, as
      well as the amounts of crystalloids, colloids, and blood products (red blood
      cells, fresh frozen plasma, platelets) administered prehospital and in the
      emergency room were compared. RESULTS: Of the 354 patients that were included,
      Standardized Mortality Ratio values decreased (indicating better survival) during
      the study period from 0.97 (pre-protocol), 0.87 (the implementation of massive
      transfusion protocol), to 0.79 (post massive transfusion protocol). The amount of
      crystalloids used in the emergency room decreased from 3870 mL (pre-protocol),
      2390 mL (the implementation of massive transfusion protocol), to 2340 mL (post
      massive transfusion protocol). In these patients, the blood products' (red blood
      cells, fresh frozen plasma, and platelets together) relation to crystalloids
      increased from 0.36, 0.70, to 0.74, respectively, in three phases. CONCLUSION:
      During the study period, no other major changes in the protocols on treatment of
      severely injured patients were implemented. The overall awareness of damage
      control fluid resuscitation and introduction of massive transfusion protocol in a
      trauma center has a significant positive effect on the outcome of severely
      injured patients.

PMID- 25989811
TI  - Plan to Have No Unplanned: A Collaborative, Hospital-Based Quality-Improvement
      Project to Reduce the Rate of Unplanned Extubations in the Pediatric ICU.
AB  - BACKGROUND: Although under-reported and understudied, unplanned extubations carry
      a significant risk of patient harm and even death. They are an important
      yardstick of quality control of care of intubated patients in the ICU. A unit
      based risk assessment and multidisciplinary approach is required to decrease the
      incidence of unplanned extubations. METHODS: As part of a quality-improvement
      initiative of Children's Hospital at Montefiore, all planned and unplanned
      extubations in a multidisciplinary 20-bed pediatric ICU were evaluated over a 12
      month period (January to December 2010). At the end of 6 months, an interim
      analysis was performed, and high-risk patient groups and patient care factors
      were identified. These factors were targeted in the second phase of the project.
      RESULTS: Over this period, there were a total of 267 extubations, of which 231
      (87%) were planned extubations and 36 (13%) were unplanned. A patient care policy
      targeting the risk factors was instituted, along with extensive nursing and other
      personnel education in the second phase. As a result of this intervention, the
      unplanned extubation rate in the pediatric ICU decreased from 3.55 to 2.59/100
      intubation days. All subjects who had an unplanned extubation during nursing
      procedures or transport required re-intubation, whereas none of the unplanned
      extubations during ventilator weaning required re-intubation. CONCLUSIONS: A
      targeted approach based on unit-specific risk factors is most effective in
      quality-improvement projects. A specific policy for sedation and weaning can be
      very helpful in managing intubated patients and preventing unintended harm.

PMID- 25989812
TI  - Noninvasive Ventilation in Mustard Airway Diseases.
AB  - BACKGROUND: Noninvasive ventilation (NIV) has been shown to improve numerous
      clinical measures in subjects with COPD, including gas exchange, exercise
      tolerance, dyspnea, hospitalizations, health-related quality of life (HRQOL), and
      functional status. Although useful for classical COPD, NIV has not been validated
      specifically as a treatment option for mustard airway disease. Our aim was to
      assess the efficacy of NIV in subjects with severe mustard airway disease.
      METHODS: This study was performed over the course of 12 months on 20 subjects
      with severe mustard airway disease (Global Initiative for Chronic Obstructive
      Lung Disease criteria). Subjects were selected from the pulmonary clinic of
      Baqiyatallah Hospital in Tehran, Iran. Body mass index, lung function, dyspnea,
      exercise tolerance, HRQOL, sleep quality, and hospitalization measures were
      assessed before and after NIV treatment. RESULTS: NIV improved HRQOL (P = .03)
      and sleep quality (P = .06) in very severe subjects and reduced hospitalizations
      (P = .003) and exacerbations (P = .01) in severe subjects. Chest imaging studies
      showed that these subjects had heterogeneous airway disease, the main finding of
      which was bronchiolitis obliterans. CONCLUSIONS: NIV can be used as an effective
      new palliative method in the treatment of mustard airway disorders. Subjects with
      very severe and severe disease benefitted differently from NIV.

PMID- 25989813
TI  - A Culture in Transition: Paramedic Experiences with Community Referral Programs.
AB  - OBJECTIVES: As an aging population continues to place strain on the health care
      system, many older adults are living with unmet social and medical needs. In
      response, Emergency Medical Services (EMS) have initiated programs that encourage
      paramedics to refer patients in need to community based support services. This
      qualitative study explores frontline paramedic experiences with referral programs
      to identify opportunities and challenges in their practice. METHODS: This study
      used an intepretivist qualitative study design involving interviews of frontline
      paramedics employed in a region where referral programs were in place. Interviews
      were semi-structured and one-on-one. Data were transcribed verbatim and analyzed
      using inductive open coding throughout, then grouped to identify themes. Data
      collection and analysis were conducted simultaneously and flexibly until
      saturation. RESULTS: Twenty-three interviews were conducted representing 6
      regions. When participating with referral programs the data revealed that
      frontline paramedics appear to experience (a) role confusion, (b) an inadequate
      knowledge base, (c) inadequate feedback, (d) undefined accountability, and (e)
      strong patient advocacy. CONCLUSIONS: In a strained health care system, EMS and
      paramedics have an opportunity to better serve patients by initiating referrals
      for patients they encounter with unmet social and medical needs. However,
      referral programs face a number of challenges that, if left poorly addressed, may
      threaten the success of such programs.

PMID- 25989814
TI  - Adherence to complementary feeding recommendations for infants and implications
      for public health.
AB  - OBJECTIVE: The current study investigates (i) the extent to which breast-feeding
      and non-breast-feeding mothers follow the Canadian Nutrition for Healthy Term
      Infants (NHTI) recommendations; (ii) the first complementary foods given and the
      differences by breast-feeding status; (iii) whether any breast-feeding is
      associated with earlier introduction to complementary foods relative to non
      breast-feeding, after controlling for potentially confounding factors; and (iv)
      the need for improvements in timing and resources of interventions by examining
      breast-feeding rates over time and information sources used by mothers. DESIGN:
      Longitudinal data from the Kingston, Frontenac, and Lennox & Addington (KFL&A)
      Infant Feeding Survey were used. Mothers completed a survey at the end of their
      hospital stay and were interviewed by telephone at 2, 4, 6 and 12 months
      thereafter. SETTING: The study took place in the KFL&A region of Ontario, Canada.
      SUBJECTS: The sample consisted of 325 mothers who gave birth to a live infant of
      at least 36 weeks' gestation and a birth weight of at least 1500 g at Kingston
      General Hospital between January and July of 2008. RESULTS: Four in five mothers
      introduced complementary foods prior to 6 months. Mothers not breast-feeding at 6
      months introduced water, juice, infant cereals, fruit and vegetables, and foods
      not recommended by Canada's Food Guide sooner than breast-feeding mothers. Breast
      feeding mothers were more likely to introduce milks appropriately, but had low
      adherence to giving their infants vitamin D supplements. CONCLUSIONS: To support
      adherence to NHTI recommendations, interventions should be conducted during early
      infancy and deliver consistent, evidence-based recommendations.

PMID- 25989815
TI  - Identification and characterization of immunodominant linear epitopes on the
      antigenic region of a serine protease in newborn Trichinella larvae.
AB  - An immunodominant serine protease of Trichinella spiralis named NBL1 showed
      encouraging potential in early diagnosis of trichinellosis in pigs and elicited
      protective immune responses during infection of animals. To further define
      serological reagents for diagnostic use, the specific epitopes on NBL protein
      recognized by the antibody responses of different susceptible hosts need to be
      defined. The present study described comprehensive mapping of immunodominant
      linear epitopes in the antigenic region (NBL-C, the C-terminal part of the
      protein) using various serum samples obtained from three kinds of hosts - pig,
      wild boar and mice. We identified six peptides which were commonly recognized by
      sera from pigs experimentally infected with Trichinella and pigs immunized with
      rNBL1-C; five and four peptides were recognized by sera from wild boars and mice
      infected with Trichinella, respectively. Three peptides (NBL1-6, -7 and -9) were
      commonly recognized by antisera in all three hosts, which share the sequence
      PSSGSRPTYP. We also found that one peptide (NBL1-12) was only recognized by
      antibodies from pigs immunized with rNBL1-C. The identification of specific
      epitopes targeted by the host antibody response is important both for
      understanding the natural response to infection and for the development of
      subunit vaccines and diagnostic tools for trichinellosis. 

PMID- 25989816
TI  - Clostridium difficile in Crete, Greece: epidemiology, microbiology and clinical
      disease.
AB  - We studied the epidemiology and microbiology of Clostridium difficile and the
      characteristics of patients with C. difficile infection (CDI) in Crete in three
      groups of hospitalized patients with diarrhoea: group 1 [positive culture and
      positive toxin by enzyme immunoassay (EIA)]; group 2 (positive culture, negative
      toxin); group 3 (negative culture, negative toxin). Patients in group 1 were
      designated as those with definitive CDI (20 patients for whom data was available)
      and matched with cases in group 2 (40 patients) and group 3 (40 patients). C.
      difficile grew from 6% (263/4379) of stool specimens; 14.4% of these had positive
      EIA, of which 3% were resistant to metronidazole. Three isolates had decreased
      vancomycin susceptibility. Patients in groups 1 and 2 received more antibiotics
      (P = 0.03) and had more infectious episodes (P = 0.03) than patients in group 3
      prior to diarrhoea. Antibiotic administration for C. difficile did not differ
      between groups 1 and 2. Mortality was similar in all three groups (10%, 12.5% and
      5%, P = 0.49). CDI frequency was low in the University Hospital of Crete and
      isolates were susceptible to metronidazole and vancomycin.

PMID- 25989817
TI  - A NOVEL SEARCH BUILDER TO EXPEDITE SEARCH STRATEGIES FOR SYSTEMATIC REVIEWS.
AB  - OBJECTIVES: Developing a search strategy for use in a systematic review is a time
      consuming process requiring construction of detailed search strings using
      complicated syntax, followed by iterative fine-tuning and trial-and-error testing
      of these strings in online biomedical search engines. METHODS: Building upon
      limitations of existing online-only search builders, a user-friendly computer
      based tool was created to expedite search strategy development as part of
      production of a systematic review. RESULTS: Search Builder 1.0 is a Microsoft
      Excel(r)-based tool that automatically assembles search strategy text strings for
      PubMed (www.pubmed.com) and Embase (www.embase.com), based on a list of user
      defined search terms and preferences. With the click of a button, Search Builder
      1.0 automatically populates the syntax needed for functional search strings, and
      copies the string to the clipboard for pasting into Pubmed or Embase. The offline
      file-based interface of Search Builder 1.0 also allows for searches to be easily
      shared and saved for future reference. CONCLUSIONS: This novel, user-friendly
      tool can save considerable time and streamline a cumbersome step in the
      systematic review process.

PMID- 25989818
TI  - Effect of ovarian hormones on the healthy equine uterus: a global gene expression
      analysis.
AB  - The physiological changes associated with the varying hormonal environment
      throughout the oestrous cycle are linked to the different functions the uterus
      needs to fulfil. The aim of the present study was to generate global gene
      expression profiles for the equine uterus during oestrus and Day 5 of dioestrus.
      To achieve this, samples were collected from five horses during oestrus (follicle
      >35 mm in diameter) and dioestrus (5 days after ovulation) and analysed using
      high-throughput RNA sequencing techniques (RNA-Seq). Differentially expressed
      genes between the two cycle stages were further investigated using Gene Ontology
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
      The expression of 1577 genes was found to be significantly upregulated during
      oestrus, whereas 1864 genes were expressed at significantly higher levels in
      dioestrus. Most genes upregulated during oestrus were associated with the
      extracellular matrix, signal interaction and transduction, cell communication or
      immune function, whereas genes expressed at higher levels in early dioestrus were
      most commonly associated with metabolic or transport functions, correlating well
      with the physiological functions of the uterus. These results allow for a more
      complete understanding of the hormonal influence on gene expression in the equine
      uterus by functional analysis of up- and downregulated genes in oestrus and
      dioestrus, respectively. In addition, a valuable baseline is provided for further
      research, including analyses of changes associated with uterine inflammation.

PMID- 25989819
TI  - The prevalence and geographic distribution of complex co-occurring disorders: a
      population study.
AB  - AIMS: A subset of people with co-occurring substance use and mental disorders
      require coordinated support from health, social welfare and justice agencies to
      achieve diversion from homelessness, criminal recidivism and further health and
      social harms. Integrated models of care are typically concentrated in large urban
      centres. The present study aimed to empirically measure the prevalence and
      distribution of complex co-occurring disorders (CCD) in a large geographic region
      that includes urban as well as rural and remote settings. METHODS: Linked data
      were examined in a population of roughly 3.7 million adults. Inclusion criteria
      for the CCD subpopulation were: physician diagnosed substance use and mental
      disorders; psychiatric hospitalisation; shelter assistance; and criminal
      convictions. Prevalence per 100 000 was calculated in 91 small areas representing
      urban, rural and remote settings. RESULTS: 2202 individuals met our inclusion
      criteria for CCD. Participants had high rates of hospitalisation (8.2
      admissions), criminal convictions (8.6 sentences) and social assistance payments
      (over $36 000 CDN) in the past 5 years. There was wide variability in the
      geographic distribution of people with CCD, with high prevalence rates in rural
      and remote settings. CONCLUSIONS: People with CCD are not restricted to areas
      with large populations or to urban settings. The highest per capita rates of CCD
      were observed in relatively remote locations, where mental health and substance
      use services are typically in limited supply. Empirically supported interventions
      must be adapted to meet the needs of people living outside of urban settings with
      high rates of CCD.

PMID- 25989820
TI  - Supramolecular Control in Nanostructured Film Architectures for Detecting Breast
      Cancer.
AB  - The need for early detection of various diseases, including breast cancer, has
      motivated research into nanomaterials that can be assembled in organized films
      which serve as biosensors. Owing to the variety of possible materials and film
      architectures, procedures are required to design optimized biosensors. In this
      study, we combine surface-specific methods to monitor the assembly of antibodies
      on nanostructured films with two distinct architectures. In the first, a layer of
      the antibody type mouse anti-HER2 (clone tab250) was immobilized on a self
      assembled monolayer (SAM) of 11-mercaptoundecanoic acid modified with N
      hydroxysuccinimide (NHS) and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide
      (EDC). In the second approach, a SAM of cysteamine was coated with a
      biotin/spreptavidin bilayer on which a layer of biotinylated antibody type
      MSx2HUp185/her biotin was adsorbed. The rougher, less passivating coating with
      cysteamine determined from cyclic voltammetry and scanning electron microscopy
      led to biosensors that are more sensitive to detect the breast cancer ERBB2
      (HER2) biomarker in impedance spectroscopy measurements. This higher
      distinguishing ability of the cysteamine-containing film architecture was proven
      with information visualization methods to treat the impedance data. Polarization
      modulated infrared reflection absorption spectroscopy (PM-IRRAS) confirmed that
      biosensing resulted from the antibody-ERBB2 antigen affinity. 

PMID- 25989821
TI  - Synthesis of Sulfoximine Carbamates by Rhodium-Catalyzed Nitrene Transfer of
      Carbamates to Sulfoxides.
AB  - Sulfoximines are of considerable interest for incorporation into medicinal
      compounds. A convenient synthesis of N-protected sulfoximines is achieved, under
      mild conditions, by rhodium-catalyzed transfer of carbamates to sulfoxides. The
      first examples of 4-membered thietane-oximines are prepared. Sulfoximines bearing
      Boc and Cbz groups are stable to further cross coupling reactions, and readily
      deprotected. This method may facilitate the preparation of NH-sulfoximines
      providing improved (global) deprotection strategies, which is illustrated in the
      synthesis of methionine sulfoxide (MSO). 

PMID- 25989822
TI  - Peroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal
      tubulointerstitial fibrosis.
AB  - AIM: Apoptosis is one of the most important mechanisms underlying renal
      tubulointerstitial fibrosis. We identified a role of protein Peroxiredoxin 1
      (Prx1) in protecting apoptosis occurred in tubular epithelial cells of the rat
      and human kidney. METHODS: Immunohistochemistry (IHC) staining was used to detect
      Prx1 expression in kidney derived from unilateral-ureteral obstruction (UUO) rats
      or patients with obstructive nephropathy. Modulation of Prx1 expression by
      transfecting siRNA and overexpression plasmid approach were carried out in NRK
      52E (rat kidney tubular epithelial cell line) cells. UUO-induced apoptosis was
      determined using TUNEL assay. RESULTS: Immunohistochemistry staining showed that
      Prx1 expressed in the cytoplasm of renal tubular epithelial cells, in the kidneys
      of UUO rats. The reduction was confirmed by both IHC and real-time polymerase
      chain reaction following a course of renal tubulointerstitial fibrosis in UUO
      rats and a decrease of Prx1 occurred concomitantly with an elevation of TUNEL
      positive cells. Fluorofenidone (AKF-PD), a new anti-tubulointerstitial fibrotic
      agent, attenuated Prx1 reduction in UUO rats. Furthermore, hydrogen peroxide (H2
      O2 )-derived oxidative stress activated p38 MAPK, and induced apoptosis in NRK
      52E cells; knockdown of Prx1 sensitized both events in NRK-52E cells, and
      overexpression of Prx1 diminished the apoptosis and the phosphorylation of p38
      CONCLUSION: Downregulation of Prx1 occurred in renal tubular epithelial cells of
      UUO rats and patients with obstructive nephropathy. Prx1 may alleviate the
      pathogenesis by inhibiting H2 O2 -induced apoptosis via inhibiting the p38 MAPK
      pathway. Prx1 may represent a useful target for a protective therapy towards
      renal tubulointerstitial fibrosis.

PMID- 25989823
TI  - Assessment of parafoveal cone density in patients taking hydroxychloroquine in
      the absence of clinically documented retinal toxicity.
AB  - PURPOSE: To measure cone density in patients taking hydroxychloroquine (HCQ),
      with no clinical evidence of maculopathy. METHODS: Patients visiting for HCQ
      macular toxicity screening in the Besancon University Hospital Ophthalmology
      Department (France) were studied. They underwent routine examination including
      spectral-domain optical coherence tomography, fundus autofluorescence and
      multifocal electroretinogram to detect HCQ-induced retinal toxicity. Cone metrics
      (density, spacing and percentage of cones with six neighbours) were obtained
      using an adaptive optics camera (RTX1, Imagine Eyes, Orsay, France). The region
      of interest corresponded to a 0.3 degrees  * 0.3 degrees  square placed nasally
      and temporally at 2 degrees  of eccentricity from the fovea. RESULTS: Forty eyes
      of 23 patients were studied. The majority of the patients (21/23) were female.
      They were aged from 25 to 60 years (mean age +/- SD: 40.1 years +/- 10). The
      cumulative dose for HCQ ranged from 24 to 2160 g (777 +/- 558 g). None of them
      displayed HCQ toxicity on screening tests. Bivariate analysis showed moderate
      cone loss with escalating doses of HCQ (linear regression, r2 = 0.23, p = 0.018).
      Cone spacing also increased with increasing cumulative dose (r2 = 0.17, p =
      0.008). Cone packing remained unchanged (p > 0.05). Multivariate analysis showed
      that age and cumulative dose were additive and independent factors of cone
      dropout. CONCLUSIONS: In this pilot study, we observed moderate cone loss as HCQ
      cumulative doses increased. The early detection of parafoveal cone metric changes
      may represent the earliest sign of HCQ macular toxicity during screening.

PMID- 25989827
TI  - Reduced Glutathione for Prevention of Renal Outcomes in Patients Undergoing
      Selective Coronary Angiography or Intervention.
AB  - OBJECTIVES: To evaluate the effect of reduced glutathione on renal outcomes
      following the selective coronary angiography and/or intervention. BACKGROUND:
      Contrast agents can cause an acute reduction in renal function that may be due to
      the generation of reactive oxygen species. The role of antioxidants in prevention
      of this renal impairment is controversial. METHODS AND RESULTS: We conducted a
      randomized, placebo-controlled trial of reduced glutathione in 825 patients who
      underwent selective coronary angiography and/or intervention. Patients were
      assigned to reduced glutathione 1800 mg (n = 416) or placebo (n = 411)
      intravenously. Contrast-induced acute kidney injury was defined by an absolute
      increase of serum creatinine >=0.5 mg/dl (44.2 MUmol/L) or a relative increase of
      >=25% measured 48 hours after the procedure. The incidence of contrast-induced
      acute kidney injury was 5.07% in the glutathione group and 4.97% in the control
      group (relative risk, 1.04; 95% confidence interval, 0.59-1.83; P = 0.886).
      Change in serum malondialdehyde was (-) 1.01 +/- 1.69 nmol/ml in the glutathione
      group and (-) 0.67 +/- 1.55 nmol/ml in the control group (P = 0.054), and change
      in serum total antioxidant capacity level was also similar in both groups (0.91
      +/- 2.06 nmol/ml and 0.79 +/- 2.18 nmol/ml, respectively; P = 0.936).
      CONCLUSIONS: A single dose of reduced glutathione does not reduce the risk of
      contrast-induced acute kidney injury in patients undergoing coronary angiography
      and/or intervention.

PMID- 25989828
TI  - Direct measurement of DNA-mediated adhesion between lipid bilayers.
AB  - Multivalent interactions between deformable mesoscopic units are ubiquitous in
      biology, where membrane macromolecules mediate the interactions between
      neighbouring living cells and between cells and solid substrates. Lately,
      analogous artificial materials have been synthesised by functionalising the outer
      surface of compliant Brownian units, for example emulsion droplets and lipid
      vesicles, with selective linkers, in particular short DNA sequences. This
      development extended the range of applicability of DNA as a selective glue,
      originally applied to solid nano and colloidal particles. On very deformable
      lipid vesicles, the coupling between statistical effects of multivalent
      interactions and mechanical deformation of the membranes gives rise to complex
      emergent behaviours, as we recently contributed to demonstrate [Parolini et al.,
      Nat. Commun., 2015, 6, 5948]. Several aspects of the complex phenomenology
      observed in these systems still lack a quantitative experimental characterisation
      and a fundamental understanding. Here we focus on the DNA-mediated multivalent
      interactions of a single liposome adhering to a flat supported bilayer. This
      simplified geometry enables the estimate of the membrane tension induced by the
      DNA-mediated adhesive forces acting on the liposome. Our experimental
      investigation is completed by morphological measurements and the characterisation
      of the DNA-melting transition, probed by in situ Forster Resonant Energy Transfer
      spectroscopy. Experimental results are compared with the predictions of an
      analytical theory that couples the deformation of the vesicle to a full
      description of the statistical mechanics of mobile linkers. With at most one
      fitting parameter, our theory is capable of semi-quantitatively matching
      experimental data, confirming the quality of the underlying assumptions. 

PMID- 25989830
TI  - Near infrared light-driven liquid crystal phase transition enabled by hydrophobic
      mesogen grafted plasmonic gold nanorods.
AB  - Light-driven phase transition in liquid crystals is a fascinating endeavour from
      both scientific and technological points of view. Here we demonstrate the proof
      of-principle that the photothermal effect of organo-soluble plasmonic gold
      nanorods can introduce the phase transition of thermotropic liquid crystals upon
      near infrared laser irradiation. Interestingly, the reverse process occurs when
      the laser is switched off. 

PMID- 25989831
TI  - Prenatal Infection and Autism Spectrum Disorders in Childhood: A Population-Based
      Case-Control Study in Taiwan.
AB  - BACKGROUND: Infection in pregnancy has long been linked with negative postnatal
      development and health. This study aims to assess the association between
      prenatal infections and autism spectrum disorders (ASDs) across three trimesters
      and to probe possible sex heterogeneity in such link. METHOD: A total of 4184
      children with incident ASDs and 16,734 matched children were identified from the
      2000-2007 National Health Insurance Research Database. For each child,
      information pertaining to the mother's infection during pregnancy,
      sociodemographics, and medical history was retrieved from healthcare records.
      Conditional logistic analyses were carried out to estimate the strength of
      associations with adjustment for multiple comparisons. RESULT: Pooled analyses
      demonstrated that having two or more outpatient visits for genital infection
      [adjusted odds ratio (aOR): 1.34; 95% confidence interval (95% CI) 1.12, 1.60;
      false discovery rate (FDR) < 0.01] and bacterial infection (aOR: 1.24; 95% CI
      1.06, 1.43; FDR < 0.05) in the third trimester were slightly associated with
      increased risk of ASDs. No statistically significant sex differences were found.
      CONCLUSION: The present study contributes updated population-based evidence about
      the connection between prenatal infection and ASDs. Potential effect of bacterial
      and genital tract infections during the third trimester on risk of ASDs warrants
      further exploration.

PMID- 25989829
TI  - Switch to etravirine for HIV-positive patients receiving statin treatment: a
      prospective study.
AB  - BACKGROUND: Lifestyle changes and statins are the cornerstones in management of
      dyslipidaemia in patients with HIV infection. Replacement of an antiretroviral
      therapy (ART) component is a proposed therapeutic strategy to reduce
      cardiovascular risk. In dyslipidaemic patients with HIV infection, we assessed
      the efficacy of replacing boosted protease inhibitor (bPI) or efavirenz (EFV) by
      etravirine (ETR) as an alternative to statin therapy. MATERIALS AND METHODS: A
      prospective, open-label, multicentre, 12-week study of patients with HIV
      infection on ART including bPI or EFV, and statin treatment. Four weeks after
      statin interruption, bPI or EFV was switched to ETR (400 mg, 8 weeks) if serum
      low-density lipoprotein cholesterol (LDL-C) was >= 3 mM. The primary endpoint was
      the proportion of patients on ETR with no indication for statin treatment at
      study completion. Serum levels of HIV RNA, lipids and biomarkers of
      cardiovascular disease were also measured. (ClinicalTrials.gov: NCT01543035).
      RESULTS: The 31 included patients had a HIV-1 RNA < 50 copies/mL (median age, 52
      years; median CD4, 709 cell/mL; median LDL-C, 2.89 mM), 68% were on EFV, and 32%
      were on bPI. At week 4, 27 patients switched to ETR. At study completion, 15
      patients (56%) on ETR did not qualify for statin treatment. After the ETR switch,
      serum levels of the cardiovascular biomarkers sICAM and MCP1/CCL2 decreased by
      11.2% and 18.9%, respectively, and those of CCL5/RANTES and tissue inhibitor of
      metalloproteinase-1 increased by 14.3% and 13.4%, respectively, indicating
      reduced cardiovascular risk. There were no notable treatment-related adverse
      events. CONCLUSIONS: Replacing bPI or EFV by ETR is a viable strategy to obviate
      primary prevention statin treatment.

PMID- 25989832
TI  - Genes and networks regulating root anatomy and architecture.
AB  - The root is an excellent model for studying developmental processes that underlie
      plant anatomy and architecture. Its modular structure, the lack of cell movement
      and relative accessibility to microscopic visualization facilitate research in a
      number of areas of plant biology. In this review, we describe several examples
      that demonstrate how cell type-specific developmental mechanisms determine cell
      fate and the formation of defined tissues with unique characteristics. In the
      last 10 yr, advances in genome-wide technologies have led to the sequencing of
      thousands of plant genomes, transcriptomes and proteomes. In parallel with the
      development of these high-throughput technologies, biologists have had to
      establish computational, statistical and bioinformatic tools that can deal with
      the wealth of data generated by them. These resources provide a foundation for
      posing more complex questions about molecular interactions, and have led to the
      discovery of new mechanisms that control phenotypic differences. Here we review
      several recent studies that shed new light on developmental processes, which are
      involved in establishing root anatomy and architecture. We highlight the power of
      combining large-scale experiments with classical techniques to uncover new
      pathways in root development.

PMID- 25989833
TI  - Blending Aboriginal and Western healing methods to treat intergenerational trauma
      with substance use disorder in Aboriginal peoples who live in northeastern
      Ontario, Canada.
AB  - As with many Indigenous groups around the world, Aboriginal communities in Canada
      face significant challenges with trauma and substance use. The complexity of
      symptoms that accompany intergenerational trauma and substance use disorders
      represents major challenges in the treatment of both disorders. There appears to
      be an underutilization of substance use and mental health services, substantial
      client dropout rates, and an increase in HIV infections in Aboriginal communities
      in Canada. The aim of this paper is to explore and evaluate current literature on
      how traditional Aboriginal healing methods and the Western treatment model
      "Seeking Safety" could be blended to help Aboriginal peoples heal from
      intergenerational trauma and substance use disorders. A literature search was
      conducted using the keywords: intergenerational trauma, historical trauma,
      Seeking Safety, substance use, Two-Eyed Seeing, Aboriginal spirituality, and
      Aboriginal traditional healing. Through a literature review of Indigenous
      knowledge, most Indigenous scholars proposed that the wellness of an Aboriginal
      community can only be adequately measured from within an Indigenous knowledge
      framework that is holistic, inclusive, and respectful of the balance between the
      spiritual, emotional, physical, and social realms of life. Their findings
      indicate that treatment interventions must honour the historical context and
      history of Indigenous peoples. Furthermore, there appears to be strong evidence
      that strengthening cultural identity, community integration, and political
      empowerment can enhance and improve mental health and substance use disorders in
      Aboriginal populations. In addition, Seeking Safety was highlighted as a well
      studied model with most populations, resulting in healing. The provided
      recommendations seek to improve the treatment and healing of Aboriginal peoples
      presenting with intergenerational trauma and addiction. Other recommendations
      include the input of qualitative and quantitative research as well as studies
      encouraging Aboriginal peoples to explore treatments that could specifically
      enhance health in their respective communities. 

PMID- 25989834
TI  - Reliability of three landmarking methods for dual inclinometry measurements of
      lumbar flexion and extension.
AB  - BACKGROUND: To examine the intra and inter-rater reliability of lumbar flexion
      and extension measurements attained using three landmarking methods for dual
      inclinometry. METHODS: This was a repeated measures reliability study.
      Convenience sampling was used to obtain forty volunteer subjects. Two assessors
      measured a series of lumbar flexion and extension movements using the J-TechTM
      dual inclinometer. Three different landmarking methods were used: 1) straight
      palpation of PSIS and L1, 2) palpation of PSIS and the site of the nearest 5 cm
      interval point closest to L1 and 3) location of PSIS and 15 cm cephalad. Upon
      landmarking, adhesive tape was used to mark landmarks and the inclinometer was
      placed on sites for three trials of flexion and extension. Tape was removed and
      landmarks were relocated by the same assessor (intra-rater) for an additional
      three trials; and this process was repeated by a second assessor (inter-rater).
      Reliability was determined using intra-class correlation coefficients. RESULTS:
      Reliability within a set of three repetitions was very high (ICCs > 0.90); intra
      rater reliability after relocating landmarks was high (ICCs > 0.80); reliability
      between therapists was moderate to high (0.60 > ICCs < 0.76). Assessment of
      flexion and extension movements by straight palpation of bony landmarks as in the
      Straight palpation of PSIS and L1 method (ICC: Flexion 0.60; Extension 0.74) was
      found to be marginally less reliable than the other two landmarking measurement
      strategies (ICC: Flexion 0.66; Extension 0.76). CONCLUSION: All three methods of
      land marking are reliable. We recommend the use of the PSIS to 15 cm cephalad
      method as used in the modified-modified Schobers test as it is the simplest to
      perform and aligns with current clinical practice.

PMID- 25989836
TI  - Immune responses in children infected with the pinworm Enterobius vermicularis in
      central Greece.
AB  - Previous studies have suggested an immunomodulatory and even protective role for
      Enterobius vermicularis, the least pathogenic human intestinal helminth. Here, in
      a study using haematological and serological parameters, we tested a total of 215
      children from central Greece, with a mean age of 8.39, of whom 105 (48.84%) were
      infected with E. vermicularis and 110 (51.16%) were matched healthy controls. In
      particular, we analysed eosinophil counts (EO), serum eosinophil cationic protein
      (ECP), total and specific serum immunoglobulin E (IgE) and the ECP/EO ratio. The
      atopic status and the potential occurrence of clinically expressed allergic
      diseases were both taken into account. Eosinophils, ECP and IgE were found to be
      higher in infected than in uninfected children, indicating a type-2 immune
      response activation during infection. Atopic infected children exhibited higher
      IgE levels compared to non-atopic ones. EO and ECP were found to be lower in
      atopic children who had a history of allergic disease than in those with no such
      history. The type-2 oriented immune response elicited against E. vermicularis
      could contribute to a balanced activation of the immune system in the examined
      children. Interestingly, although the atopic children showed a stronger
      activation, they did not exhibit any symptoms and, moreover, there seemed to be
      some indication of immunosuppression in those children with a positive history of
      allergic disease. 

PMID- 25989835
TI  - Were sea level changes during the Pleistocene in the South Atlantic Coastal Plain
      a driver of speciation in Petunia (Solanaceae)?
AB  - BACKGROUND: Quaternary climatic changes led to variations in sea level and these
      variations played a significant role in the generation of marine terrace deposits
      in the South Atlantic Coastal Plain. The main consequence of the increase in sea
      level was local extinction or population displacement, such that coastal species
      would be found around the new coastline. Our main goal was to investigate the
      effects of sea level changes on the geographical structure and variability of
      genetic lineages from a Petunia species endemic to the South Atlantic Coastal
      Plain. We employed a phylogeographic approach based on plastid sequences obtained
      from individuals collected from the complete geographic distribution of Petunia
      integrifolia ssp. depauperata and its sister group. We used population genetics
      tests to evaluate the degree of genetic variation and structure among and within
      populations, and we used haplotype network analysis and Bayesian phylogenetic
      methods to estimate divergence times and population growth. RESULTS: We observed
      three major genetic lineages whose geographical distribution may be related to
      different transgression/regression events that occurred in this region during the
      Pleistocene. The divergence time between the monophyletic group P. integrifolia
      ssp. depauperata and its sister group (P. integrifolia ssp. integrifolia) was
      compatible with geological estimates of the availability of the coastal plain.
      Similarly, the origin of each genetic lineage is congruent with geological
      estimates of habitat availability. CONCLUSIONS: Diversification of P.
      integrifolia ssp. depauperata possibly occurred as a consequence of the marine
      transgression/regression cycles during the Pleistocene. In periods of high sea
      level, plants were most likely restricted to a refuge area corresponding to
      fossil dunes and granitic hills, from which they colonized the coast once the sea
      level came down. The modern pattern of lineage geographical distribution and
      population variation was established by a range expansion with serial founder
      effects conditioned on soil availability.

PMID- 25989837
TI  - Determining content for a simulation-based curriculum in pediatric emergency
      medicine: results from a national Delphi process.
AB  - OBJECTIVES: By the end of residency training, pediatric emergency medicine (PEM)
      residents are expected to have developed the confidence and abilities required to
      manage acutely ill children. Acquisition of competence requires exposure and/or
      supplemental formal education for critical and noncritical medical clinical
      presentations. Simulation can provide experiential learning and can improve
      trainees' knowledge, skills, and attitudes. The primary objective of this project
      was to identify the content for a simulation-based national curriculum for PEM
      training. METHODS: We recruited participants for the Delphi study by contacting
      current PEM program directors and immediate past program directors as well as
      simulation experts at all of the Canadian PEM fellowship sites. We determined the
      appropriate core content for the Delphi study by combining the PEM core content
      requirements of the Royal College of Physicians and Surgeons of Canada (RCPSC)
      and the American Board of Pediatrics (ABP). Using the Delphi method, we achieved
      consensus amongst the national group of PEM and simulation experts. The
      participants completed a three-round Delphi (using a four-point Likert scale).
      RESULTS: Response rates for the Delphi were 85% for the first round and 77% for
      second and third rounds. From the initial 224 topics, 53 were eliminated (scored
      <2). Eighty-five topics scored between 2 and 3, and 87 scored between 3 and 4.
      The 48 topics, which were scored between 3.5 and 4.0, were labeled as "key
      curriculum topics." CONCLUSION: We have iteratively identified a consensus for
      the content of a national simulation-based curriculum.

PMID- 25989838
TI  - Lunch frequency among adolescents: associations with sociodemographic factors and
      school characteristics.
AB  - OBJECTIVE: To investigate: (i) how lunch frequency of adolescents varies between
      schools and between classes within schools; (ii) the associations between
      frequency of lunch and individual sociodemographic factors and school
      characteristics; and (iii) if any observed associations between lunch frequency
      and school characteristics vary by gender and age groups. DESIGN: Cross-sectional
      study in which students and school headmasters completed self-administered
      questionnaires. Associations were estimated by multilevel multivariate logistic
      regression. SETTING: The Danish arm of the Health Behaviour in School-Aged
      Children study 2010. SUBJECTS: Students (n 4922) aged 11, 13 and 15 years
      attending a random sample of seventy-three schools. RESULTS: The school-level and
      class-level variations in low lunch frequency were small (intraclass correlation
      coefficient <2.1 %). At the individual level, low lunch frequency was most common
      among students who were boys, 13- and 15-year-olds, from medium and low family
      social class, descendants of immigrants, living in a single-parent family and in
      a reconstructed family. School-level analyses suggested that having access to a
      canteen at school was associated with low lunch frequency (OR=1.47; 95% CI 1.14,
      1.89). Likewise not having an adult present during lunch breaks was associated
      with low lunch frequency (OR=1.44; 95% CI 1.18, 1.75). Cross-level interactions
      suggested that these associations differed by age group. CONCLUSIONS: Lunch
      frequency among Danish students appears to be largely influenced by
      sociodemographic factors. Additionally, the presence of an adult during lunch
      breaks promotes frequent lunch consumption while availability of a canteen may
      discourage frequent lunch consumption. These findings vary between older and
      younger students.

PMID- 25989840
TI  - Assessment of medical students' proficiency in dermatology: Are medical students
      adequately prepared to diagnose and treat common dermatologic conditions in the
      United States?
AB  - This study assessed whether a current medical school curriculum is adequately
      preparing medical students to diagnose and treat common dermatologic conditions.
      A 15-item anonymous multiple choice quiz covering fifteen diseases was developed
      to test students' ability to diagnose and treat common dermatologic conditions.
      The quiz also contained five items that assessed students' confidence in their
      ability to diagnose common dermatologic conditions, their perception of whether
      they were receiving adequate training in dermatology, and their preferences for
      additional training in dermatology. The survey was performed in 2014, and was
      completed by 85 students (79.4%). Many students (87.6%) felt that they received
      inadequate training in dermatology during medical school. On average, students
      scored 46.6% on the 15-item quiz. Proficiency at the medical school where the
      study was performed is considered an overall score of greater than or equal to
      70.0%. Students received an average score of 49.9% on the diagnostic items and an
      average score of 43.2% on the treatment items. The findings of this study suggest
      that United States medical schools should consider testing their students and
      assessing whether they are being adequately trained in dermatology. Then schools
      can decide if they need to re-evaluate the timing and delivery of their current
      dermatology curriculum, or whether additional curriculum hours or clinical
      rotations should be assigned for dermatologic training. 

PMID- 25989839
TI  - EFFICACY OF CARPENTIER-EDWARDS PERICARDIAL PROSTHESES: A SYSTEMATIC REVIEW AND
      META-ANALYSIS.
AB  - OBJECTIVES: The Carpentier-Edwards pericardial (CEP) prostheses are the type of
      bioprostheses most used worldwide. Although they were designed to minimize the
      rate of valve deterioration and reoperation, their clinical superiority over
      other prostheses models still lacks confirmation. The objective of this study was
      to evaluate its effectiveness. METHODS: We performed a systematic review and meta
      analysis in the PubMed, Embase, Cochrane, and Lilacs databases. Operative
      mortality, overall mortality and reoperation rates after heart valve surgery were
      compared between the use of CEP and other cardiac prostheses. Two independent
      reviewers screened studies for inclusion and extracted the data. Disagreements
      were resolved by consensus. The GRADE criterion was used to assess the evidence
      quality. RESULTS: A total of twenty-eight studies were selected, including 19,615
      individuals. The studies presented a high heterogeneity and low quality of
      evidence what limited the reliability of the results. The pooled data from the
      selected studies did not demonstrate significant differences between CEP and
      porcine, pericardial or stentless prostheses regarding operative mortality,
      overall mortality and reoperation rates. However, the pooled data from 3
      observational trials pointed out a higher risk for reoperation after valve
      replacement using CEP prostheses against mechanical prostheses (OR 4.92 [95
      percent confidence interval 2.43-9.96]). CONCLUSIONS: The current data present in
      the literature still does not support a clinical advantage for the use of CEP
      prostheses over other bioprostheses. The quality of the studies in the literature
      is limited and further studies are needed to address if CEP prostheses will have
      a clinical advantage over other prostheses.

PMID- 25989841
TI  - Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of
      available diagnostic tests.
AB  - Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a
      diagnostic challenge as more than 50% of patients remain without an aetiology.
      The introduction of polymerase chain reaction (PCR) and arboviral serologies have
      increased diagnostic capabilities, yet large scale epidemiological studies
      evaluating their use in clinical practice are lacking. We conducted a prospective
      observational study in New Orleans between November 1999 and September 2008
      (early era) when PCR was not widely available, and in Houston between November
      2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting
      with meningitis and negative CSF-GS were followed for 4 weeks. All
      investigations, PCR used, and results were recorded as they became available. In
      323 patients enrolled, PCR provided the highest diagnostic yield (24.2%) but was
      ordered for 128 (39.6%) patients; followed by serology for arboviruses (15%) that
      was ordered for 100 (31%) of all patients. The yield of blood cultures was
      (10.3%) and that of CSF cultures was 4%; the yield for all other tests was <10%.
      Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72.1% in
      early era vs. 53.4% (P < 0.01) in modern era; this change was attributed to
      diagnosing more viral pathogens, 8.3% and 26.3% (P < 0.01), respectively. The
      introduction of PCR and arboviral serologies has improved the yield of diagnosing
      patients with meningitis and a negative CSF-GS, but both tests are being under
      utilized.

PMID- 25989843
TI  - Genomic expression profiles in cumulus cells derived from germinal vesicle and
      MII mouse oocytes.
AB  - Cumulus cells (CCs) are distinct from other granulosa cells and the mutual
      communication between CCs and oocytes is essential for the establishment of
      oocyte competence. In the present study we assessed genomic expression profiles
      in mouse CCs before and after oocyte maturation in vitro. Microarray analysis
      revealed significant changes in gene expression in CCs between the germinal
      vesicle (GV) and metaphase II (MII) stages, with 2615 upregulated and 2808
      downregulated genes. Genes related to epidermal growth factor, extracellular
      matrix (Ptgs2, Ereg, Tnfaip6 and Efemp1), mitochondrial metabolism (Fdx1 and
      Aifm2), gap junctions and the cell cycle (Gja1, Gja4, Ccnd2, Ccna2 and Ccnb2)
      were highlighted as being differentially expressed between the two development
      stages. Real-time polymerase chain reaction confirmed the validity and
      reproducibility of the results for the selected differentially expressed genes.
      Similar expression patterns were identified by western blot analysis for some
      functional proteins, including EFEMP1, FDX1, GJA1 and CCND2, followed by
      immunofluorescence localisation. These genes may be potential biomarkers for
      oocyte developmental competence following fertilisation and will be investigated
      further in future studies.

PMID- 25989842
TI  - BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia
      cells.
AB  - The bromodomain (BRD) and extraterminal (BET) proteins including BRD2, BRD3 and
      BRD4 have been identified as key targets for leukemia maintenance. A novel oral
      inhibitor of BRD2/3/4, the thienotriazolodiazepine compound OTX015, suitable for
      human use, is available. Here we report its biological effects in AML and ALL
      cell lines and leukemic samples. Exposure to OTX015 lead to cell growth
      inhibition, cell cycle arrest and apoptosis at submicromolar concentrations in
      acute leukemia cell lines and patient-derived leukemic cells, as described with
      the canonical JQ1 BET inhibitor. Treatment with JQ1 and OTX15 induces similar
      gene expression profiles in sensitive cell lines, including a c-MYC decrease and
      an HEXIM1 increase. OTX015 exposure also induced a strong decrease of BRD2, BRD4
      and c-MYC and increase of HEXIM1 proteins, while BRD3 expression was unchanged. c
      MYC, BRD2, BRD3, BRD4 and HEXIM1 mRNA levels did not correlate however with
      viability following exposure to OTX015. Sequential combinations of OTX015 with
      other epigenetic modifying drugs, panobinostat and azacitidine have a synergic
      effect on growth of the KASUMI cell line. Our results indicate that OTX015 and
      JQ1 have similar biological effects in leukemic cells, supporting OTX015
      evaluation in a Phase Ib trial in relapsed/refractory leukemia patients.

PMID- 25989844
TI  - Adult attention-deficit/hyperactivity disorder and its association with substance
      use and substance use disorders in young men.
AB  - BACKGROUND: Functional and mental health impairments that adults with attention
      deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular
      substance use and co-morbidity with substance use disorders (SUD). This may be
      especially true during young adulthood, which represents a critical stage of life
      associated with increased substance use and associated problems. However,
      previous studies investigating the association between ADHD and substance use and
      SUD have demonstrated inconsistent results, probably due to methodological
      limitations (e.g., small and non-representative samples). Thus, the relationship
      of ADHD with substance use and related disorders remains unclear. The aim of the
      present study was to examine the association between ADHD and both the use of
      licit and illicit substances and the presence of SUD in a large, representative
      sample of young men. METHOD: The sample included 5677 Swiss men (mean age 20 +/-
      1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C
      SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The
      association between ADHD and substance use and SUD was assessed for alcohol,
      nicotine, cannabis and other illicit drugs, while controlling for socio
      demographic variables and co-morbid psychiatric disorders (i.e., major depression
      (MD) and anti-social personality disorder (ASPD)). RESULTS: Men with ADHD were
      more likely to report having used nicotine, cannabis and other illicit drugs at
      some time in their life, but not alcohol. ADHD was positively associated with
      early initiation of alcohol, nicotine and cannabis use, the risky use of these
      substances, and the presence of alcohol use disorders, and nicotine and cannabis
      dependence. Additionally, our analyses revealed that these patterns are also
      highly associated with ASPD. After adjusting for this disorder, the association
      between ADHD and licit and illicit substance use and the presence of SUDs was
      reduced, but remained significant. CONCLUSIONS: Our findings suggest that adult
      ADHD is significantly associated with a propensity to experiment with licit and
      illicit substances, especially at earlier ages, to exhibit risky substance use
      patterns, and to subsequently develop SUDs. Preventive strategies that include
      early intervention and addressing co-morbidity with ASPD may be crucial to
      reducing substance use and the development of pathological substance use patterns
      in young men affected by ADHD and, thus, helping to prevent further illness
      burden later in life.

PMID- 25989845
TI  - Oxidative Stress Correlates (OSC) in Diabetes Mellitus Patients.
AB  - BACKGROUND/AIM: Diabetes mellitus (DM) is a considerable systemic metabolic
      disorder to exhibit various metabolic and cardiovascular disorders, mainly
      hyperglycemia. Our study aims to evaluate oxidative stress markers in DM patients
      and to determine the clinical correlates affecting the investigational
      parameters. METHODOLOGY: To evaluate oxidative stress, the following parameters
      were included: tri-glycerides(TG), total cholesterol, low density lipoprotein
      cholesterol(LDL), oxidized LDL cholesterol(Ox LDL), superoxide dismutase(SOD),
      glutathione peroxidase(GSH-Px) and plasminogen activator inhibitor(PAI) which
      were measured at single observation point. Patient clinical and demographic data
      were taken from registered medication profiles from the Outpatient Department.
      RESULTS: The diabetic subjects have significantly high measured values of
      endocrine(p<0.01), metabolic(p<0.01) and antioxidant parameters(p<0.05), and have
      significant higher values of TG(3.69+/-1.27 vs 1.79+/-0.84 mmol/L, p< 0.01), Ox
      LDL(85.37+/-19.1 vs 77.11+/-26.64 mmol/L, p<0.05) and SOD enzyme activity(918.78
      +/- 145.39 vs 880.08+/-149.52 U/g Hb, p<0.05) compared to the controls. A
      significant negative correlation was found between Ox LDL and HbA1c(r = -0.6782,
      p < 0.001) among diabetic subjects. CONCLUSION: Elevated Ox-LDL, SOD and GSH-Px
      are associated with the diabetic patients. However, oxidative stress threshold
      values also showed high oxidative activity markers among controls. Clinical
      variables showed predictive information on oxidative activity among diabetes
      patients.

PMID- 25989846
TI  - Palladium-Catalyzed sp(3) C-H Nitration of 8-Methylquinolines.
AB  - Palladium-catalyzed nitration of 8-methylquinolines with t-BuONO to give 8
      (nitromethyl)quinolines in moderate to excellent yields has been developed
      involving an sp(3) C-H bond activation. The resulting (nitromethyl)quinolines
      could be selectively reduced to (1,2,3,4-tetrahydroquinolin-8-yl)methanamines by
      NaBH4 in the presence of a catalytic amount of NiCl2.6H2O. 

PMID- 25989847
TI  - Dielectric Effects at Organic/Inorganic Interfaces in Nanostructured Devices.
AB  - Dielectric interfaces are important in organic electronic devices, as they
      dominate charge generation and recombination dynamics and set the tone for
      efficiency of the device. In a charge separation scenario across the interface,
      we calculate the binding energy of a charge carrier for variations in dielectric
      mismatch (i.e., the ratio of the dielectric constant of materials forming the
      interface), interface shape and size, and dielectric anisotropy. We find that
      dielectric mismatch results in binding of the charge carrier to the interface
      with energies on the order of several kT. For the variation in interface shape
      and size, epitomized by the device morphology, we show that the assumption of a
      planar interface overestimates the attractive potential. The change in the
      interface curvature affects the binding energy of the charge carrier by order of
      kT. Anisotropy is shown to affect critically the electric field along the
      principal axis, while the binding energy of the charge is altered by more than 5
      kT. We are able to give an upper limit on the change in the binding energy for
      the variations in the above interfacial factors. These limits can serve as
      guidelines for optimization, interface engineering, and design of high efficiency
      organic electronic devices. 

PMID- 25989848
TI  - Are Molecules Involved in Neuritogenesis and Axon Guidance Related to Autism
      Pathogenesis?
AB  - Autism spectrum disorder is a heterogeneous disease, and numerous alterations of
      gene expression come into play to attempt to explain potential molecular and
      pathophysiological causes. Abnormalities of brain development and connectivity
      associated with alterations in cytoskeletal rearrangement, neuritogenesis and
      elongation of axons and dendrites might represent or contribute to the structural
      basis of autism pathology. Slit/Robo signaling regulates cytoskeletal remodeling
      related to axonal and dendritic branching. Components of its signaling pathway
      (ABL and Cdc42) are suspected to be molecular bases of alterations of normal
      development. The present review describes the most important mechanisms
      underlying neuritogenesis, axon pathfinding and the role of GTPases in neurite
      outgrowth, with special emphasis on alterations associated with autism spectrum
      disorders. On the basis of analysis of publicly available microarray data,
      potential biomarkers of autism are discussed. 

PMID- 25989849
TI  - Acute and subchronic effects on immune responses of carp (Cyprinus carpio L.)
      after exposure to deoxynivalenol (DON) in feed.
AB  - The mycotoxin deoxynivalenol (DON) has been shown to regularly occur at relevant
      concentrations in feed designed for aquaculture use, but little is known about
      the consequences of its presence on the organisms that consume the DON
      contaminated feed. Previous studies indicated a down-regulation of pro
      inflammatory responses in carp (Cyprinus carpio L.) after 4 weeks of feeding DON.
      The present study examined the time course of innate immune responses of carp to
      orally administered DON. Changes in mRNA levels of immune genes in different
      organs (head kidney, trunk kidney, spleen, liver, and intestine) were observed
      indicating immune-modulating properties of DON. The immune-modulatory effects
      during the acute phase of DON exposure were characterized by the activation of
      both pro- and anti-inflammatory cytokines and enzymes in carp. The subchronic
      responses to DON were characterized by activation of arginases culminating in
      increased arginase activity in head kidney leukocytes after 26 days of DON
      treatment. These results suggest profound effects of this mycotoxin on fish in
      aquaculture.

PMID- 25989850
TI  - Defining a rational step-care algorithm for managing thyroid carcinoma patients
      with elevated thyroglobulin and negative on radioiodine scintigraphy (TENIS):
      considerations and challenges towards developing an appropriate roadmap.

PMID- 25989851
TI  - Pedunculopontine cell loss and protein aggregation direct microglia activation in
      parkinsonian rats.
AB  - We previously reported a loss of cholinergic neurons within the pedunculopontine
      tegmental nucleus (PPTg) in rats that had been intra-nigrally lesioned with the
      proteasomal inhibitor lactacystin, with levels of neuronal loss corresponding to
      that seen in the post-mortem pedunculopontine nucleus (PPN) of advanced
      Parkinson's disease (PD) patients. Here we reveal lower expression values of the
      acetylcholine synthesising enzyme, choline acetyltransferase, within the
      remaining PPTg cholinergic neurons of lesioned rats compared to sham controls. We
      further characterise this animal model entailing dopaminergic- and non
      dopaminergic neurodegeneration by reporting on stereological counts of non
      cholinergic neurons, to determine whether the toxin is neuro-type specific. Cell
      counts between lesioned and sham-lesioned rats were analysed in terms of the
      topological distribution pattern across the rostro-caudal extent of the PPTg. The
      study also reports somatic hypotrophy in the remaining non-cholinergic neurons,
      particularly on the side closest to the nigral lesion. The cytotoxicity affecting
      the PPTg in this rat model of PD involves overexpression and accumulation of
      alpha-synuclein (alphaSYN), affecting cholinergic and non-cholinergic neurons as
      well as microglia on the lesioned hemispheric side. We ascertained that microglia
      within the PPTg become fully activated due to the extensive neuronal damage and
      neuronal death resulting from a lactacystin nigral lesion, displaying a distinct
      rostro-caudal distribution profile which correlates with PPTg neuronal loss, with
      the added implication that lactacystin-induced alphaSYN aggregation might trigger
      neuronophagia for promoting PPTg cell loss. The data provide critical insights
      into the mechanisms underlying the lactacystin rat model of PD, for studying the
      PPTg in health and when modelling neurodegenerative disease.

PMID- 25989853
TI  - Actin dynamics shape microglia effector functions.
AB  - Impaired actin filament dynamics have been associated with cellular senescence.
      Microglia, the resident immune cells of the brain, are emerging as a central
      pathophysiological player in neurodegeneration. Microglia activation, which
      ranges on a continuum between classical and alternative, may be of critical
      importance to brain disease. Using genetic and pharmacological manipulations, we
      studied the effects of alterations in actin dynamics on microglia effector
      functions. Disruption of actin dynamics did not affect transcription of genes
      involved in the LPS-triggered classical inflammatory response. By contrast, in
      consequence of impaired nuclear translocation of phospho-STAT6, genes involved in
      IL-4 induced alternative activation were strongly downregulated. Functionally,
      impaired actin dynamics resulted in reduced NO secretion and reduced release of
      TNFalpha and IL-6 from LPS-stimulated microglia and of IGF-1 from IL-4 stimulated
      microglia. However, pathological stabilization of the actin cytoskeleton
      increased LPS-induced release of IL-1beta and IL-18, which belong to an
      unconventional secretory pathway. Reduced NO release was associated with
      decreased cytoplasmic iNOS protein expression and decreased intracellular
      arginine uptake. Furthermore, disruption of actin dynamics resulted in reduced
      microglia migration, proliferation and phagocytosis. Finally, baseline and ATP
      induced [Ca(2+)]int levels were significantly increased in microglia lacking
      gelsolin, a key actin-severing protein. Together, the dynamic state of the actin
      cytoskeleton profoundly and distinctly affects microglia behaviours. Disruption
      of actin dynamics attenuates M2 polarization by inhibiting transcription of
      alternative activation genes. In classical activation, the role of actin
      remodelling is complex, does not relate to gene transcription and shows a major
      divergence between cytokines following conventional and unconventional secretion.

PMID- 25989852
TI  - Individual variation in the neural processes of motor decisions in the stop
      signal task: the influence of novelty seeking and harm avoidance personality
      traits.
AB  - Personality traits contribute to variation in human behavior, including the
      propensity to take risk. Extant work targeted risk-taking processes with an
      explicit manipulation of reward, but it remains unclear whether personality
      traits influence simple decisions such as speeded versus delayed responses during
      cognitive control. We explored this issue in an fMRI study of the stop signal
      task, in which participants varied in response time trial by trial, speeding up
      and risking a stop error or slowing down to avoid errors. Regional brain
      activations to speeded versus delayed motor responses (risk-taking) were
      correlated to novelty seeking (NS), harm avoidance (HA) and reward dependence
      (RD), with age and gender as covariates, in a whole brain regression. At a
      corrected threshold, the results showed a positive correlation between NS and
      risk-taking responses in the dorsomedial prefrontal, bilateral orbitofrontal, and
      frontopolar cortex, and between HA and risk-taking responses in the
      parahippocampal gyrus and putamen. No regional activations varied with RD. These
      findings demonstrate that personality traits influence the neural processes of
      executive control beyond behavioral tasks that involve explicit monetary reward.
      The results also speak broadly to the importance of characterizing inter-subject
      variation in studies of cognition and brain functions.

PMID- 25989854
TI  - Evaluating the efficacy of bioremediating a diesel-contaminated soil using
      ecotoxicological and bacterial community indices.
AB  - Diesel represents a common environmental contaminant as a result of operation,
      storage, and transportation accidents. The bioremediation of diesel in a
      contaminated soil is seen as an environmentally safe approach to treat
      contaminated land. The effectiveness of the remediation process is usually
      assessed by the degradation of the total petroleum hydrocarbon (TPH)
      concentration, without considering ecotoxicological effects. The aim of this
      study was to assess the efficacy of two bioremediation strategies in terms of
      reduction in TPH concentration together with ecotoxicity indices and changes in
      the bacterial diversity assessed using PCR-denaturing gradient gel
      electrophoresis (DGGE). The biostimulation strategy resulted in a 90 % reduction
      in the TPH concentration versus 78 % reduction from the natural attenuation
      strategy over 12 weeks incubation in a laboratory mesocosm-containing diesel
      contaminated soil. In contrast, the reduction in the ecotoxicity resulting from
      the natural attenuation treatment using the Microtox and earthworm toxicity
      assays was more than double the reduction resulting from the biostimulation
      treatment (45 and 20 % reduction, respectively). The biostimulated treatment
      involved the addition of nitrogen and phosphorus in order to stimulate the
      microorganisms by creating an optimal C:N:P molar ratio. An increased
      concentration of ammonium and phosphate was detected in the biostimulated soil
      compared with the naturally attenuated samples before and after the remediation
      process. Furthermore, through PCR-DGGE, significant changes in the bacterial
      community were observed as a consequence of adding the nutrients together with
      the diesel (biostimulation), resulting in the formation of distinctly different
      bacterial communities in the soil subjected to the two strategies used in this
      study. These findings indicate the suitability of both bioremediation approaches
      in treating hydrocarbon-contaminated soil, particularly biostimulation. Although
      biostimulation represents a commercially viable bioremediation technology for use
      in diesel-contaminated soils, further research is required to determine the
      ecotoxicological impacts of the intervention.

PMID- 25989855
TI  - Ecological status classification of the Taizi River Basin, China: a comparison of
      integrated risk assessment approaches.
AB  - Integrated risk assessment approaches allow to achieve a sound evaluation of
      ecological status of river basins and to gain knowledge about the likely causes
      of impairment, useful for informing and supporting the decision-making process.
      In this paper, the integrated risk assessment (IRA) methodology developed in the
      EU MODELKEY project (and implemented in the MODELKEY Decision Support System) is
      applied to the Taizi River (China), in order to assess its Ecological and
      Chemical Status according to EU Water Framework Directive (WFD) requirements. The
      available dataset is derived by an extensive survey carried out in 2009 and 2010
      across the Taizi River catchment, including the monitoring of physico-chemical
      (i.e. DO, EC, NH3-_N, chemical oxygen demand (COD), biological oxygen demand in 5
      days (BOD5) and TP), chemical (i.e. polycyclic aromatic hydrocarbons (PAHs) and
      metals), biological (i.e. macroinvertebrates, fish, and algae), and
      hydromorphological parameters (i.e. water quantity, channel change and morphology
      diversity). The results show a negative trend in the ecological status from the
      highland to the lowland of the Taizi River Basin. Organic pollution from
      agriculture and domestic sources (i.e. COD and BOD5), unstable hydrological
      regime (i.e. water quantity shortage) and chemical pollutants from industry (i.e.
      PAHs and metals) are found to be the main stressors impacting the ecological
      status of the Taizi River Basin. The comparison between the results of the IRA
      methodology and those of a previous study (Leigh et al. 2012) indicates that the
      selection of indicators and integrating methodologies can have a relevant impact
      on the classification of the ecological status. The IRA methodology, which
      integrates information from five lines of evidence (i.e., biology, physico
      chemistry, chemistry, ecotoxicology and hydromorphology) required by WFD, allows
      to better identify the biological communities that are potentially at risk and
      the stressors that are most likely responsible for the observed alterations. This
      knowledge can be beneficial for a more effective restoration and management of
      the river basin ecosystem.

PMID- 25989856
TI  - Risk analysis on heavy metal contamination in sediments of rivers flowing into
      Nansi Lake.
AB  - In order to understand the risk of heavy metals in sediments of the rivers
      flowing into Nansi Lake, 36 surface sediments were sampled from six rivers and
      seven heavy metals (Cr, Cu, Ni, Zn, As, Pb, and Cd) were determined. Potential
      ecological risk index (RI) of the six rivers showed significant differences:
      Xinxue River, Jiehe River, and Guangfu River were at medium potential risk,
      whereas the risk of Chengguo River was the lowest. Jiehe River, Xuesha River, and
      Jiangji River were meeting the medium potential risk at river mouths. Geo
      accumulation index (I geo) of the seven heavy metals revealed that the
      contamination of Cu and Cd was more serious than most other metals in the studied
      areas, whereas Cr in most sites of our study was not polluted. Moreover,
      correlation cluster analysis demonstrated that the contamination of Cu, Ni, and
      Zn in six rivers was mainly caused by local emissions, whereas that of As, Pb,
      and Cd might come from the external inputs in different forms. Consequently, the
      contamination of Cu and Cd and the potential risk in Xinxue River, Jiehe River,
      and Guangfu River as well as the local emissions should be given more attention
      to safeguard the water quality of Nansi Lake and the East Route Project of South
      to North Water Transfer.

PMID- 25989857
TI  - Trace element fluxes in sediments of an environmentally impacted river from a
      coastal zone of Brazil.
AB  - Data regarding trace element concentrations and fluxes in suspended sediments and
      bedload are scarce. To fill this gap and meet the international need to include
      polluted rivers in future world estimation of trace element fluxes, this study
      aimed to determine the trace element fluxes in suspended sediment and bedload of
      an environmentally impacted river in Brazil. Water, suspended sediment, and
      bedload from both the upstream and the downstream cross sections were collected.
      To collect both the suspended sediment and water samples, we used the US DH-48.
      Bedload measurements were carried out using the US BLH 84 sampler. Concentrations
      of Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn were determined by inductively coupled
      plasma (ICP-OES). As and Hg were determined by an atomic absorption
      spectrophotometer (AA-FIAS). The suspended sediments contributed more than 99 %
      of the trace element flux. By far Pb and to a less extent Zn at the downstream
      site represents major concerns. The yields of Pb and Zn in suspended sediments
      were 4.20 and 2.93 kg km(2) year(-1), respectively. These yields were higher than
      the values reported for Pb and Zn for Tuul River (highly impacted by mining
      activities), 1.60 and 1.30 kg km(2) year(-1), respectively, as well as the Pb
      yield (suspended + dissolved) to the sea of some Mediterranean rivers equal to
      3.4 kg km(2) year(-1). Therefore, the highest flux and yield of Pb and Zn in
      Ipojuca River highlighted the importance to include medium and small rivers-often
      overlooked in global and regional studies-in the future estimation of world trace
      element fluxes in order to protect estuaries and coastal zones.

PMID- 25989858
TI  - Management of sewage sludge by composting using fermented water hyacinth.
AB  - The goal of the present research work was to assess the management of sewage
      sludge (SS) by composting using fermented water hyacinth (WHferm) as an
      amendment. The water hyacinth was fermented, and a higher production of volatile
      fatty acids (VFAs) (782.67 mg L(-1)) and soluble organic carbon (CSOL) (4788.34
      mg L(-1)) was obtained using a particle size of 7 mm compared to 50 mm. For
      composting, four treatments (10 kg fresh weight each) were evaluated: treatment A
      (100 % SS + 0 % WHferm), treatment B (75 % SS + 25 % WHferm), treatment C (50 %
      SS + 50 % WHferm), and treatment D (25 % SS + 75 % WHferm). The WHferm added to
      SS, especially in treatments C (50 %) and D (75 %), increased the initial
      contents of organic matter (OM), organic carbon (CORG), CSOL, the C/N ratio, and
      the germination index (GI). The heavy metal content (HMC) (As, Cd, Cr, Cu, Hg,
      Ni, Pb, and Zn) at the beginning was below the maximum allowed by USEPA
      regulations. All of the samples were free of Salmonella sp. from the beginning.
      The reduction of the CORG, CSOL, total Kjeldahl nitrogen (TKN), and C/N ratio
      indicated the degradation of the OM by day 198. The treatments with WHferm (B, C,
      and D) yielded higher values of electrical conductivity, cation exchange
      capacity, and GI than SS at day 198. No significant differences were observed in
      GI among the treatments with WHferm. The fecal coliforms were eliminated (<3 MPN
      g(-1)) and the helminths were reduced to <=5 eggs/2 g during the process. The
      competition for nutrients and the presence of suppressive fungi of the genera
      Penicillium, Rhizopus, Paecilomyces (penicillin producers), and Fusariella
      isolated from the compost may have promoted the elimination of pathogens since no
      thermophile temperatures were obtained. WHferm as an amendment in the composting
      of SS improved the characteristics of the final product, especially when it was
      used in proportions of 25 and 50 %. An excellent product was obtained in terms of
      HMC, and the product was B class in terms of pathogens.

PMID- 25989859
TI  - Insecticidal activity of Jatropha curcas extracts against housefly, Musca
      domestica.
AB  - The hexane and ether extracts of leaves, bark and roots of Jatropha curcas were
      screened for their toxicity against different developmental stages of housefly.
      The larvicidal, pupicidal and adulticidal activities were analysed at various
      concentrations (0.78-7.86 mg/cm(2)) of hexane and ether extracts. The lethal
      concentration values (LC50) of hexane extract of J. curcas leaves were 3.0 and
      0.27 mg/cm(2) for adult and larval stages of housefly, respectively, after 48 h.
      Similarly, the ether extract of leaf showed the LC50 of 2.20 and 4.53 mg/cm(2)
      for adult and larval stages of housefly. Least toxicity was observed with hexane
      root extract of J. curcas with LC50 values of 14.18 and 14.26 mg/cm(2) for adult
      and larvae of housefly, respectively, after 48 h. The variation in LC50 against
      housefly pupae was found to be 8.88-13.10 mg/cm(2) at various J. curcas extract
      concentrations. The GC-MS analysis of J. curcas leaf extract revealed the
      presence of trans-phytol (60.81 %), squalene (28.58 %), phytol (2.52 %) and
      nonadecanone (1.06 %) as major components that could be attributed for
      insecticidal activity of J. curcas extracts.

PMID- 25989860
TI  - Environmental exposure to organochlorine pesticides and deficits in cochlear
      status in children.
AB  - The aim of this study was to examine the hypothesis that organochlorine
      pesticides (OCPs), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta
      HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) and its
      metabolite 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'- DDE) are ototoxic
      to humans. A multivariate general linear model was designed, in which the
      statistical relation between blood serum concentrations of HCB, beta-HCH, p,p'
      DDT, or p,p'-DDE at different ages (at birth, 6, 16, and 45 months) and the
      distortion product otoacoustic emissions (DPOAEs) was treated as multivariate
      outcome variables. Polychlorinated biphenyl (PCB) congeners and OCPs were
      strongly correlated in serum of children from our cohort. To ascertain that the
      association between DPOAEs at a given frequency and concentration of a pesticide
      is not influenced by PCBs or other OCP also present in serum, we calculated
      benchmark concentrations (BMCs) relating DPOAEs to a serum pesticide alone and in
      presence of confounding PCB-153 or other OCPs. We found that BMCs relating DPOAEs
      to serum pesticides are not affected by confounders. DPOAE amplitudes were
      associated with serum OCPs at all investigated time intervals, however, in a
      positive way with prenatal exposure and in a negative way with all postnatal
      exposures. We observed tonotopicity in the association of pesticides with
      amplitude of DPOAEs as its strength was frequency dependent. We conclude that
      exposure to OCPs in infancy at environmental concentrations may be associated
      with hearing deficits.

PMID- 25989861
TI  - Hydrocarbon concentration and source appraisal in atmospheric particulate matter
      (PM2.5) of an urban tropical area.
AB  - Polycyclic aromatic (46 PAHs) and aliphatic hydrocarbons (C12-C40) were studied
      in atmospheric particulate matter sampled in Rio de Janeiro Metropolitan Area
      (RJMA). In total, 236 samples from six different sites were collected
      simultaneously and weekly over 1 year (January-December 2011) allowing a robust
      atmospheric characterization of fine particulate matter (PM2.5). Hydrocarbon
      concentration was in general low compared to previous studies in the area (PAHs
      range 0.25-19.3 ng m(-3)), possibly due to changes in fuel composition over time.
      Precipitation is the main meteorological parameter that rules particulate and
      hydrocarbon concentration, modifying PAH typology by scavenging. Aliphatic and
      aromatic diagnostic ratios gave indications conflicting with combustion features.
      However, ratios showed differences among sites. Principal component analysis
      (PCA) associated to multiple linear regressions (MLR) allowed quantitative
      estimate of sources and effectively indicated vehicular emission as the main
      hydrocarbon source in the atmospheric particulate matter.

PMID- 25989862
TI  - Occurrence and distribution of polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDD/Fs) in industrial and domestic sewage sludge.
AB  - Sewage sludge samples collected from 43 different domestic and industrial
      wastewater treatment plants and petrochemical industries that discharge to the
      Houston Ship Channel (HSC) were analyzed for polychlorinated dibenzo-p-dioxins
      and polychlorinated dibenzofurans (PCDD/Fs), which are highly toxic and
      carcinogenic towards humans and animals. The measured total PCDD/F toxic
      equivalency (TEQ) ranged between 0.73 and 7348.40 pg/g dry weight. The mean TEQ
      of PCDD/Fs in industrial sludge was approximately 40 times higher than that in
      sewage sludge. The PCDD homolog concentrations in the industrial samples were
      higher than those observed at the wastewater treatment plants by a factor of 10,
      with total heptachlorodibenzodioxin (HpCDD) exhibiting the maximum concentration
      in most of the samples. Among the PCDF homologs, total heptadichlorodibenzofuran
      (HpCDF) dominated the total homolog concentration in sludge from the wastewater
      treatment plants, whereas total tetradichlorodibenzofuran (TeCDF) dominated the
      industrial sludge samples. Overall, the total PCDD/F TEQ in sludge samples was
      much higher than that in effluent samples from the same facility. A linear
      correlation (R (2) = 0.62, p value < 0.068) was found indicating that sludge
      sampling can be used as a surrogate for effluent concentrations in wastewater
      treatment plants but not for industrial discharges.

PMID- 25989864
TI  - When to recommend allogeneic transplant in multiple myeloma.
AB  - Utilization of allogeneic transplant in the management of multiple myeloma has
      been actively pursued for nearly 30 years. In this paper, the existing data for
      use of transplant is reviewed as primary therapy, as salvage and for genetic high
      risk disease. The relative merits of using a matched-unrelated donor vs. an HLA
      matched donor and what impact the introduction of the novel agents has on the
      decision to transplant will be covered. 

PMID- 25989863
TI  - Phenolic profile of Dunaliella tertiolecta growing under high levels of copper
      and iron.
AB  - The present study investigates the phenolic profile of exudates and extracts of
      the green algae Dunaliella tertiolecta, harvested in natural seawater in the
      absence (control) and in the presence of Cu(II) (315 and 790 nmol L(-1)) and
      Fe(III) (900 nmol L(-1)) in order to identify and quantify the phenolic compounds
      produced under metallic stress conditions. The presence of metal ions modifies
      the growth of cells and changes cell metabolism by producing phenolic compounds
      adapted to the solution. The use of reversed-phase high-performance liquid
      chromatography (RP-HPLC) permitted the identification of 14 phenolic
      constituents. The concentration and type of polyphenols detected in cell extracts
      and in solution are directly related with the metal and its concentration during
      growth cultures, achieving 1.4 times higher levels of polyphenols under 790 nmol
      Cu(II) L(-1) with respect to the control experiments. Microalga excretes
      polyphenols to be adapted to the environmental conditions. Gentisic acid, (+)
      catechin and (-) epicatechin, the most prominent phenolic compounds detected in
      the algae extracts, showed high antioxidant activity in inhibiting 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radicals. This potent activity may be related to its
      presence in cells and exudates in high concentrations.

PMID- 25989865
TI  - Exploring the role of bone marrow increased FDG uptake on PET/CT in patients with
      lymphoma-associated hemophagocytic lymphohistiocytosis: a reflection of bone
      marrow involvement or cytokine storm?
AB  - The role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) uptake of bone marrow (BM) on
      positron emission tomography/computed tomography (PET/CT) in patients with
      lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) remains
      uncertain. This retrospective study included 34 LA-HLH patients who underwent
      both PET/CT and comprehensive BM examinations prior to treatment. Comparison
      between PET/CT and BM examinations for the assessment of bone marrow involvement
      (BMI) indicated statistical difference (p = 0.039). The specificity of PET/CT in
      detecting BMI was 11.1% compared to BM examinations. However, a significant
      correlation was found between PET parameters of BM and laboratory parameters
      associated with HLH, such as C-reactive protein, ferritin, fibrinogen and soluble
      CD25. By multivariate analysis, PET parameters of marrow were significantly
      associated with overall survival. The findings suggest that FDG uptake of marrow
      might fail to detect lymphomatous BMI, but reflected the level of cytokine storm
      to a certain extent and might be a prognostic factor in patients with LA-HLH.

PMID- 25989866
TI  - Acute acquired comitant esotropia of childhood: a classification based on 48
      children.
AB  - PURPOSE: To identify characteristics of pediatric patients who develop acute
      acquired comitant esotropia (AACE) with and without intracranial disease.
      METHODS: We reviewed the charts of 48 children consecutively referred to the
      hospital with AACE during a 13-year period. Inclusion criteria were acute onset
      of comitant esotropia, available data on ophthalmologic, orthoptic and neurologic
      examinations. Children with neurological signs, AACE recurrence or hyperopia <+3
      dioptres (D) underwent brain computed tomography or magnetic resonance imaging.
      Patients without imaging were followed. RESULTS: In all, 48 cases were recorded.
      The mean age at onset was 4.7 years, being significantly higher among children
      with intracranial disease. Seven cause-specific types of AACE in childhood were
      identified: The acute accommodative (n = 15, 31%), decompensated monofixation
      syndrome or esophoria (n = 13, 27%), idiopathic (n = 9, 19%), intracranial
      disease (n = 3, 6%), occlusion related (n = 3, 6%), AACE secondary to different
      aetiologic disease (n = 3, 6%) and cyclic AACE (n = 2, 4%). Intracranial disease
      included hydrocephalus, pontine and thalamic glioma. Of the children with
      intracranial disease, 2 of 3 had no obvious neurological signs at onset. Four
      significant risk factors for intracranial disease were identified as follows:
      larger esodeviation at distance, recurrence of AACE, neuro signs (papilledema)
      and older age at onset (>6 years). CONCLUSION: In a large case series of children
      with AACE and by review of literature, we identified seven cause-specific types
      of AACE. Intracranial disease was present in 6%, and four risk factors were
      identified to guide clinicians when to perform brain imaging. Findings suggest
      AACE of childhood to be differentiated from AACE of adulthood.

PMID- 25989867
TI  - A novel technique for laparoscopic inguinal hernia repair in children: single
      port laparoscopic percutaneous extraperitoneal closure assisted by an optical
      forceps.
AB  - AIM: The aim of this study was to describe and report the results of our new
      pediatric inguinal hernia repair technique, in which single-port laparoscopic
      percutaneous extraperitoneal closure (SPEC) technique was modified by using
      optical foreign-body forceps (OFF) of the rigid bronchoscope. MATERIALS AND
      METHODS: Between January 2012 and January 2014, a total of 79 children who were
      operated using SPEC assisted with OFF (SPEC-OFF) were included in this study.
      Demographic and clinical features of the children were obtained and reviewed
      retrospectively. RESULTS: Ninety-nine hernia repairs were performed on a total of
      79 children (51 boys, 28 girls). All of the patients were operated by SPEC-OFF
      without the need of introducing extra forceps, with or without an additional
      trocar. The mean operating time was 17.6 +/- 5.5 min. The mean follow-up period
      was 17.5 +/- 7.1 months. There were six recurrences (two boys, four girls). No
      wound infection, hydroceles or testicular atrophy occurred in any patients during
      post-surgery follow-up. The technique left a very small scar with excellent
      cosmesis in the umbilicus and groin area. CONCLUSIONS: SPEC-OFF is a simple, safe
      and effective technique for laparoscopic inguinal hernia repair, and for
      determining contralateral hernia. There is no need to use additional working
      forceps for the technique and the surgeon can perform the procedure without any
      assistance for laparoscope.

PMID- 25989870
TI  - Generalized infantile myofibromatosis with a monophasic primitive pattern.
AB  - Infantile myofibromatosis (IM) is a rare disorder present at birth or in early
      infancy with a biphasic histological pattern. We present a neonatal-onset case of
      generalized IM with visceral (central nervous system, heart, lungs, liver,
      spleen, small intestine, kidneys and bones) and placental involvement, showing a
      monophasic histological pattern through the lesions during the course of disease.
      Histologically, the tumor was composed of a solid proliferation of cytologically
      uniform, 'primitive' mesenchymal cells associated with a hemangiopericytoma-like
      vascular pattern. Immunohistochemical analysis and ultrastructural study revealed
      that the tumor cells exhibited primitive features without mature myofibroblastic
      differentiation. Neither ETV6-NTRK3 nor ACTB-GLI fusion gene was identified. The
      patient died of cerebral hemorrhage and respiratory failure at four months of age
      despite intensive therapy. Generalized IM characterized by monophasic primitive
      pattern could be related to poor clinical outcome. 

PMID- 25989868
TI  - Population Pharmacokinetics of Darbepoetin Alfa in Conjunction with Hypothermia
      for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.
AB  - AIM: The aim of this study was to determine the population pharmacokinetics of
      darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy
      treated with hypothermia. METHODS: Neonates >=36 weeks gestation and <12 h
      postpartum with moderate to severe hypoxic-ischemic encephalopathy who were
      undergoing hypothermia treatment were recruited in this randomized, multicenter,
      investigational, new drug pharmacokinetic study. Two intravenous darbepoetin alfa
      treatment groups were evaluated: 2 and 10 ug/kg. Serum erythropoietin
      concentrations were measured using an enzyme-linked immunosorbent assay. Monolix
      4.3.1 was used to estimate darbepoetin alfa clearance and volume of distribution.
      Covariates tested included: birthweight, gestational age, postnatal age,
      postmenstrual age, sex, Sarnat score, and study site. RESULTS: Darbepoetin alfa
      pharmacokinetics were well described by a one-compartment model with exponential
      error. Clearance and the volume of distribution were scaled by birthweight
      (centered on the mean) a priori. Additionally, gestational age (also centered on
      the mean) significantly affected darbepoetin alfa clearance. Clearance and volume
      of distribution were estimated as 0.0465 L/h (95% confidence interval 0.0392
      0.0537) and 1.58 L (95% confidence interval 1.29-1.87), respectively.
      CONCLUSIONS: A one-compartment model successfully described the pharmacokinetics
      of darbepoetin alfa among hypothermic neonates treated for hypoxic-ischemic
      encephalopathy. Clearance decreased with increasing gestational age.

PMID- 25989872
TI  - Community structure and soil pH determine chemoautotrophic carbon dioxide
      fixation in drained paddy soils.
AB  - Previous studies suggested that microbial photosynthesis plays a potential role
      in paddy fields, but little is known about chemoautotrophic carbon fixers in
      drained paddy soils. We conducted a microcosm study using soil samples from five
      paddy fields to determine the environmental factors and quantify key functional
      microbial taxa involved in chemoautotrophic carbon fixation. We used stable
      isotope probing in combination with phospholipid fatty acid (PLFA) and molecular
      approaches. The amount of microbial (13)CO2 fixation was determined by
      quantification of (13)C-enriched fatty acid methyl esters and ranged from 21.28
      to 72.48 ng of (13)C (g of dry soil)(-1), and the corresponding ratio (labeled
      PLFA-C:total PLFA-C) ranged from 0.06 to 0.49%. The amount of incorporationof
      (13)CO2 into PLFAs significantly increased with soil pH except at pH 7.8. PLFA
      and high-throughput sequencing results indicated a dominant role of Gram-negative
      bacteria or proteobacteria in (13)CO2 fixation. Correlation analysis indicated a
      significant association between microbial community structure and carbon
      fixation. We provide direct evidence of chemoautotrophic C fixation in soils with
      statistical evidence of microbial community structure regulation of inorganic
      carbon fixation in the paddy soil ecosystem.

PMID- 25989873
TI  - Aflibercept versus ranibizumab for treating persistent diabetic macular oedema.
AB  - The purpose of this study was to compare the efficacy of intravitreal aflibercept
      versus ranibizumab for treating therapy-resistant diabetic macular oedema (DME).
      A 69-year-old man presented with persistent bilateral DME despite previous
      ranibizumab treatment. Bilateral study treatment comprised one cycle of three
      monthly ranibizumab injections (0.5 mg), followed by one cycle of three
      aflibercept injections (2.0 mg), a second ranibizumab cycle and a second
      aflibercept cycle. Baseline visual acuity (ETDRS score) was 60 letters for the
      right eye and 65 letters for the left eye. Baseline central foveal thickness
      (CFT) was 305 MUm for the right eye and 453 MUm for the left eye. Substantially
      improved outcomes were observed during the first aflibercept cycle. CFT was
      reduced by 150 MUm (mean) in both the eyes and decreased below the lowest level
      achieved during the previous 2.5-year ranibizumab treatment. Visual acuity was
      improved by 17.5 letters (mean) in both the eyes. Reintroduction of ranibizumab
      immediately worsened the status of both eyes back to the baseline level. During
      the final aflibercept cycle, visual acuity and CFT improved to the same levels
      achieved during the first aflibercept cycle. In this case study, we prospectively
      switched the treatment three times and observed a dramatic and consistent
      treatment advantage for aflibercept.

PMID- 25989875
TI  - [Magnetic urethral closure device. Negative outcome after implantation for the
      treatment of female urinary incontinence].
AB  - We report on a negative outcome after implantation of a magnetic urethral closure
      device, consisting of one part screwed into the pubic bone and one part as a
      vaginal cone, for the treatment of urinary stress incontinence grade III.
      Continence was never achieved for the patient. The urethra narrowed over time due
      to erosion and scarring and the patient started intermittent catheterization,
      because spontaneous micturition was not possible. The magnet was broken, the
      bladder neck was eroded, several fragments were found in the bladder, and
      numerous fragments were scattered throughout the small pelvis. Surgery consisted
      of removing most of the fragments, followed by bladder neck closure and
      suprapubic diversion. 

PMID- 25989876
TI  - [Research activities of the GeSRU Academics urological infections group. Projects
      that pave the way for the best group performance].

PMID- 25989874
TI  - [Evaluation of testicular volume in 0- to 18-year-old boys by sonography].
AB  - BACKGROUND: Reference values are necessary in clinical practice in order to
      correctly evaluate testicular volume and detect disorders. OBJECTIVES: The
      objective of this prospective cross-sectional study was to evaluate reference
      values for testicular volume dependent on age, height, and weight in boys aged 0
      18 years. MATERIAL AND METHODS: During their inpatient stay, the testes of 174
      boys, who were free of disease or therapy that might influence testicular
      development, were examined by sonography. High resolution ultrasound transducers
      ranging from 7.5-14 MHz were used for evaluation. The testicular volume was
      calculated by the ellipsoid formula: length * width * height * (pi/6). RESULTS:
      The subject age ranged from 0-18 years (average 7.1 +/- 5.3 years). At the age of
      0-8 years, the left testicular volume (1.2 ml) was less than the right testicular
      volume (1.3 ml). At the age of 13 years, the testicular volume of all subjects
      was over 3 ml. Left testicular volume of boys aged 16.5-18 years ranged from 7 to
      22 ml and the right testicular volume ranged from 6 to 22 ml. CONCLUSION:
      Reference value tables of testicular volume dependent on age, and for the first
      time dependent on weight and height in boys aged from 0-18 years were compiled.
      Tables of testicular length, width, and height dependent on age are provided.

PMID- 25989877
TI  - Inflammation induced at different developmental stages affects differently the
      range of microglial reactivity and the course of seizures evoked in the adult
      rat.
AB  - BACKGROUND: In the brain, inflammation occurs following a variety of types of
      brain damage, including epileptic seizures. Proinflammatory cytokines, like IL
      1beta or TNFalpha, can increase neuronal excitability and initiate spontaneous
      seizures or epileptogenesis. Recent studies indicate that the effects can be
      attenuated or even abolished in animals subjected to inflammation-inducing
      treatments at earlier developmental stages, termed "preconditioning".
      Immunocompetent microglial cells display particular sensitivity to subtle brain
      pathologies showing a morphological continuum from resting to reactive forms.
      Following inflammation, multiple ramified processes of resting microglia become
      gradually shorter, and the cells transform into macrophages. Parameters of the
      morphological variations were used here as indicators of the nervous tissue
      reactivity to seizures in adult rats experiencing inflammation at earlier stages
      of postnatal development. METHODS: Systemic inflammation was induced with
      lipopolysaccharide (LPS) in 6-day-old or 30-day-old rats. In two-month-old
      survivors of the inflammatory status, seizures were evoked with pilocarpine
      injection. The seizure intensity was scored during a six-hour continuous
      observation period following the injection. Brain sections were immunostained for
      Iba1 to visualize microglia. Thereafter, morphology of microglial cells located
      in the hippocampal formation was analyzed using parameters such as solidity,
      circularity, ramification index, and area. RESULTS: In naive rats, seizure
      induced transformations of microglial cells were reflected by strong changes in
      the parameters of their morphology. However, in the adult rats pretreated with
      LPS on their 6th or 30th postnatal days, the seizure-induced changes were
      significantly reduced, and microglial morphology remained significantly closer to
      normal. Significant amelioration of the acute phase of seizures was observed only
      when inflammation was induced in 30-day-old, but not in 6-day-old, rats.
      CONCLUSIONS: The results confirm previous reports that moderate inflammation
      protects the nervous tissue from subsequent damage by reducing influences of
      proinflammatory factors on reactive glial cells. The young-age inflammation may
      have age-dependent effects on susceptibility to seizures induced in adulthood.
      This article is part of a Special Issue entitled "Status Epilepticus".

PMID- 25989878
TI  - An evaluation of lateralizing signs in patients with temporal lobe epilepsy.
AB  - Resective epilepsy surgery has been accepted as an effective treatment for
      patients with medically intractable temporal lobe epilepsy (TLE) to control the
      seizures and to limit cognitive dysfunction. Complete resection of the epileptic
      zone, and therefore the success of the surgery, depends on the identification of
      the seizure focus. Reliable lateralizing semiologic signs, together with other
      presurgical assessments, are of great importance for an accurate identification
      of the seizure focus. In this respect, this study evaluated the frequency of
      semiologic signs in medically intractable temporal lobe epilepsy (TLE) together
      with the lateralizing values and variations according to the age and gender
      groups. Two hundred seventy-three seizures of 55 patients of the Adult Epilepsy
      Monitoring Unit of Gazi University Faculty of Medicine with the diagnosis of
      medically intractable TLE, whose epileptic foci were detected through noninvasive
      presurgical procedures and seizures were controlled successfully after anterior
      temporal lobectomy (ATL), were analyzed retrospectively. Seizure semiologies of
      the patients were evaluated in terms of lateralizing values, and it was inquired
      whether age/gender causes any variation. Versive head rotation, unilateral
      dystonic limb posturing, asymmetric tonic limb posturing, and the combination of
      unilateral hand automatisms and dystonic posturing were determined as the
      semiologic signs with the highest lateralizing values (90-100%). While hand
      automatisms were observed frequently in the group with early seizure-onset age
      (onset age <= 2), asymmetric tonic limb posturing was detected as more frequent
      in the group with later seizure-onset age (onset age > 2; p < .005). In addition
      to this, semiologic signs were noted to be different between male and female
      groups; psychic and autonomic auras and ictal emotional signs were associated
      with women (p < .005).

PMID- 25989879
TI  - Chilling of Steindachneridionparahybae (siluriformes: pimelodidae) embryos.
AB  - The objective of this study was to assess the viability of Steindachneridion
      parahybae embryos after chilling using different cryoprotectant solutions, stages
      of embryonic development, chilling curves, and storage periods at temperatures
      between -10  degrees C and 0  degrees C. Three experimental tests were conducted,
      and the following aspects were evaluated: (1) the toxicity of six cryoprotectant
      solutions (10% methanol, ethylene glycol, or DMSO combined with 0.5-M sucrose or
      lactose); (2) viability of embryos submitted to cooling with two cryoprotectant
      solutions (10% or 20% methanol combined with 10-M sucrose) at three different
      stages of development (closure of blastoporus, appearance of the optic vesicle
      and the moment when the tail began to straighten out), and two chilling periods
      (6 and 12 hours); (3) viability of embryos submitted to cooling with three
      chilling curves (directly to the freezer without a curve, 0.5  degrees C/min and
      1.0  degrees C/min) and two chilling periods (6 and 12 hours). After the tests,
      it was concluded that the protocol which presented the most positive results
      after chilling, with a hatching rate of 63.50 +/- 9.98% of the embryos and 12.32
      +/- 3.85% normal hatched larvae, was the one with embryos at the free-tail stage,
      the cryoprotectant solution with 10% methanol and 10-M sucrose, a chilling curve
      of 0.5  degrees C/min, stored for a maximum of 6 hours at subzero temperatures
      (temperature ranging between -5.05  degrees C and -7.83  degrees C). 

PMID- 25989881
TI  - A Mo-doped TiNb2O7 anode for lithium-ion batteries with high rate capability due
      to charge redistribution.
AB  - Mo-doped TiNb2O7 (TNO) anode material has shown excellent electrochemical
      performance, especially at high C-rates. Doping TNO with Mo(6+) resulted in
      charge redistribution, leading to the enhancement of electronic conductivity
      (caused by bandgap narrowing) and Li(+) diffusivity in the lattice. 

PMID- 25989880
TI  - Impaired antioxidant HDL function is associated with premature myocardial
      infarction.
AB  - BACKGROUND: There is growing evidence that the predictive value of HDL
      cholesterol levels for cardiovascular risk stratification is limited in patients
      with coronary artery disease (CAD). HDL function seems to be a more sensitive
      surrogate of cardiovascular risk estimation than simple serum levels. Therefore,
      we aimed to assess whether impaired antioxidant HDL function is involved in the
      development of premature acute myocardial infarction (AMI). METHODS: In this
      multicentre case-control study, we compared the antioxidant function of HDL,
      measured by the HDL inflammatory index (HII), and HDL particle size in 184
      patients comprising 92 patients with AMI at a very young age (<=40 years of age)
      and 92 age- and gender-matched controls. RESULTS: Antioxidant capacities of HDL
      were significantly impaired in the acute phase of AMI (HII of 1.50 [IQR 1.10
      1.74] vs. 0.56 [IQR 0.41-0.86] in controls, P < 0.001 as well as in the chronic
      stable phase 1 year after the event (HII of 0.85 [IQR 0.72-1.03] vs. 0.56 [IQR
      0.41-0.86], P < 0.001) compared to controls. Moreover, HDL function in the stable
      phase remained significantly associated with premature MI in adjusted logistic
      regression analysis with an OR of 2.24 per SD increase of HII (95% CI 1.28-3.91;
      P = 0.005). Analyses of HDL size revealed a significant correlation between all
      HDL subfractions and HDL function in controls, whereas this correlation was lost
      for large and intermediate HDL in AMI patients. CONCLUSION: Impaired antioxidant
      function of HDL is independently associated with the development of premature
      AMI. The maintenance of HDL function might evolve into a significant therapeutic
      target, especially in patients with premature CAD.

PMID- 25989882
TI  - Crystallographic dependence of photocatalytic activity of WO3 thin films prepared
      by molecular beam epitaxy.
AB  - We investigated the impact of crystallographic orientation on the photocatalytic
      activity of single crystalline WO3 thin films prepared by molecular beam epitaxy
      on the photodegradation of rhodamine B (RhB). A clear effect is observed, with
      (111) being the most reactive surface, followed by (110) and (001).
      Photoreactivity is directly correlated with the surface free energy determined by
      density functional theory calculations. The RhB photodegradation mechanism is
      found to involve hydroxyl radicals in solution formed from photo-generated holes
      and differs from previous studies performed on nanoparticles and composites. 

PMID- 25989883
TI  - Captopril therapy limits ventricular remodeling but does not alter myocardial
      collagen fiber morphology of cardiomyopathic hamsters.
AB  - Previous studies of the effect of angiotensin-converting enzyme (ACE) inhibitors
      on the process of cardiac remodeling have devoted little attention to potentially
      beneficial alterations in collagen fiber morphology and microscopic organization.
      The present work is part of a continuing effort to define mechanisms responsible
      for changes in microscopic material properties of cardiac tissue that are induced
      by such pharmacologic therapy. Morphologic evaluation of 11 cardiomyopathic (CM)
      and 5 control hamsters was performed. Six CM hamsters received captopril for 3
      months in their drinking water (2 gm/l), and five other CM hamsters and five
      normal control hamsters received no treatment. Myocyte and collagen content,
      organization, and fiber size were defined with the use of circular statistics in
      fixed sections that were stained with picrosirius red and viewed with polarized
      light. The scar regions from both treated and untreated CM hearts manifested
      similar collagen fiber thicknesses, organization (angular deviation 21.1 +/- 0.7
      degrees vs. 19.2 +/- 2.2 degrees, untreated vs. treated, p = NS), and content
      (65.0% +/- 2.2% vs. 65.7% +/- 3.7%, untreated vs. treated, p = NS). However,
      significant muscle fiber disarray was observed in myocytes in the non-necrotic
      zones near scars for both treated and untreated CM heart, and a strong trend
      toward normalization of myocyte alignment was observed after captopril therapy.
      In the present study, captopril exerted no significant effect on collagen
      content, two-dimensional fiber organization, or fiber thickness in either scar or
      nonscar regions. Thus, the beneficial effects of captopril on cardiac material
      properties in ventricular remodeling associated with heritable cardiomyopathy
      does not appear to be related to alterations in collagen fiber morphology or
      organization. However, the trend toward normalization of myocyte alignment
      induced by captopril in non-necrotic zones suggests a possible mechanism for the
      known beneficial effects of captopril on favorable ventricular remodeling. 

PMID- 25989884
TI  - The healed and sealed aortic intimomedial tear.
AB  - A retrospective study of surgical pathology and autopsy material revealed eight
      examples of intimomedial tears that had healed with the tear sealed or
      obliterated by fibromuscular tissue; four were the result of iatrogenic trauma
      related to application of aortic cross clamps during surgery and four developed
      spontaneously. The former were single lesions, the latter all associated with
      other intimomedial tears. Iatrogenic/traumatic tears occurred in ascending aortas
      that had histologically normal medias, spontaneous ones were located at sites
      where intimal tears are found and affected aortas with diseased medias.
      Observations in these cases suggest a triphasic process in the pathogenesis of
      dissecting aneurysms involving an intimal tear, hemorrhage into the resultant
      defect, and a hemorrhagic dissection of the media. These processes do not
      necessarily follow in sequence so the mechanism of each must be understood. The
      size and morphology of healed and sealed intimomedial tears indicate some might
      be detectable by ultrasonography and/or other imaging techniques. They seem
      uncommon but could be missed by both imagers and pathologists. 

PMID- 25989885
TI  - Subset of vascular dendritic cells transforming into foam cells in human
      atherosclerotic lesions.
AB  - It has been previously demonstrated that S-100 positive vascular dendritic cells
      are involved in human atherosclerosis and they usually show a low level of
      accumulation of lipids in their cytoplasm, even though they located among foam
      cells and cellular debris in atherosclerotic lesions. During ongoing
      immunohistochemical investigations, however, we have found that a few S-100
      positive cells exhibited a foam cell appearance. Therefore, we undertook an
      electronmicroscopic examination to see if any foam cells exhibit the distinctive
      features of vascular dendritic cells such as the presence of dense granules and a
      tubulovesicular system uniquely found in well differentiated dendritic cells.
      Foam cells exhibiting the typical characteristics of vascular dendritic cells
      were indeed found. Their cytoplasm contained a large number of lipid vacuoles and
      cisterns of the tubulovesicular system as well as dense granules which, in
      contrast to lysosomes present in macrophages, did not transform into
      phagolysosomes. The formation of a central lamina inside cisterns of the
      tubulovesicular system was also detected. These pentalaminal structures,
      comprised of two parallel limiting membranes and a central lamina, are similar to
      the Birbeck granules present in human epidermal Langerhans cells. From our
      present observations we speculate that the defense mechanisms against extensive
      lipid accumulation may be broken in some vascular dendritic cells, causing them
      to transform into foam cells. 

PMID- 25989886
TI  - Lysosomal enzyme release from human neutrophils adherent to foreign material
      surfaces: enhanced release of elastase activity.
AB  - Neutrophils are the major phagocytic white blood cell present during the acute
      inflammatory response to cardiovascular medical devices and can become activated
      to release a wide variety of products that help mediate the overall host
      response. The purpose of this investigation was to develop an in vitro system to
      study the release of lysosomal enzymes from neutrophils adherent to biomaterial
      surfaces. Neutrophils isolated from peripheral human blood were allowed to adhere
      to different biomaterials and lysosomal enzyme release assessed by monitoring
      elastase-like activity in the supernatant. The number of adherent neutrophils
      with intact cytoplasmic membranes was estimated by extracting the cells and
      quantifying lactate dehydrogenase. Stimulated and non-stimulated neutrophils
      released significantly different amounts of elastase-like activity depending on
      the biomaterial surface to which they were adhered. The techniques developed in
      this study form the basis of an in vitro system for investigating the events
      associated with neutrophil/biomaterial interactions as well as a method for
      evaluating the white blood cell response to the materials used in circulatory
      support devices. 

PMID- 25989887
TI  - Lactobacillus endocarditis: a chronic active infection.
AB  - Lactobacilli are gram positive rod-shaped or filamentous bacteria that are a rare
      cause of endocarditis. We review the literature of less than 50 reported cases,
      and present a case of a 43-year-old male with a protracted, one-year history
      consistent with endocarditus. The pathologic findings in the heart at autopsy
      indicate a long, chronic course of smoldering infection with extensive secondary
      fibroelastosis of valvular structure and adjacent endocardium, although
      superimposed more acute vegetation with viable organisms consistent with the
      premortem blood culture of Lactobacillus acidophilus were abuntly present. Thus,
      the pathologic and clinical features of this case, and our review of the
      available literature, suggest that infective endocarditis caused by Lactobacillus
      species has an indolent nature and results in severe, chronic alterations of
      valvular structure. 

PMID- 25989888
TI  - Cardiac pseudopyogenic granuloma: a type of vascular hyperplasia in the
      transplanted heart mimicking pyogenic granuloma.
AB  - We present a unique case of cardiac pseudopyogenic granuloma in a 61-year-old man
      that underwent orthotopic heart transplantation for end-stage ischemic heart
      disease. The lesion was an incidental pathological finding in the allograft
      removed for chronic graft vascular disease. This lesion is attributed to the
      minor trauma of the biopsy in the right side of the heart following cardiac
      transplantation. The cardiac right side can be considered the venous side of the
      heart; therefore, we consider the lesion a mimicker of an intravenous pyogenic
      granuloma. Pseudopyogenic granuloma may represent organization of a mural
      thrombus which formed secondary to biopsy procedure(s). The lesion must be
      distinguished from bacillary angiomatosis, Karposi sarcoma, and other neoplasms
      that may present an intravascular type of growth. 

PMID- 25989889
TI  - Modeling approach for multiple transporters-mediated drug-drug interactions in
      sandwich-cultured human hepatocytes: effect of cyclosporin A on hepatic
      disposition of mycophenolic acid phenyl-glucuronide.
AB  - A lower exposure of mycophenolic acid (MPA) in patients receiving MPA-mofetil in
      combination with cyclosporin A (CsA) is thought to be due to the inhibition of
      enterohepatic circulation of phenyl-glucuronide of MPA (MPAG). This study aimed
      to evaluate the interaction of CsA with hepatic disposition of MPA and MPAG in
      sandwich-cultured human hepatocytes (SCHH) by a mathematical modeling approach.
      In addition, the inhibition of CsA for glucuronidation of MPA to MPAG was
      examined in human liver microsomes. Inhibitory parameters of CsA for hepatic
      disposition of MPAG were estimated using a non-linear mixed effect model program,
      NONMEM. As a result, CsA did not influence the conversion of MPA to MPAG in
      either SCHH or human liver microsomes. In contrast, CsA inhibited the basolateral
      uptake of MPAG with an estimated maximum inhibitory effect (Imax) of 32.4%. CsA
      also inhibited basolateral efflux and biliary excretion of MPAG formed in SCHH,
      and the concentration producing 50% of Imax (IC50) for biliary excretion was
      lower than that for basolateral efflux. Our modeling approach suggests that CsA
      inhibits both basolateral uptake and biliary excretion of MPAG and leads to
      changes in systemic exposure of MPA and MPAG in humans.

PMID- 25989890
TI  - Relationship between ABCB1 gene polymorphisms and severe neutropenia in patients
      with breast cancer treated with doxorubicin/cyclophosphamide chemotherapy.
AB  - Chemotherapy-induced neutropenia is one of the major adverse events which results
      in the reduction of chemotherapy. Doxorubicin is a substrate of the adenosine
      triphosphate-binding cassette subfamily B member 1 (ABCB1) transporter;
      reportedly, ABCB1 polymorphisms influence doxorubicin pharmacokinetics. We
      evaluated the association between chemotherapy-induced neutropenia and ABCB1
      polymorphisms in patients with breast cancer. We investigated 141 patients with
      breast cancer treated with doxorubicin and cyclophosphamide (AC) chemotherapy.
      Peripheral blood samples obtained from patients were genotyped for the ABCB1
      2677G>T/A and 3435C>T polymorphisms. The genotypes were then investigated for
      their association with grade 3 or greater neutropenia, and further their risk
      factors were examined using a multivariate logistic regression. The proportion of
      patients with grade 3 or greater neutropenia was 85.7% in the homozygous variant
      group, and 80% and 58.6% in the heterozygous variant and GG genotype groups,
      respectively (p = 0.021). The multivariate logistic regression analysis revealed
      that the ABCB1 2677G>T/A polymorphism was a strong predictor of grade 3 or
      greater neutropenia (odds ratio: 3.76; 95% confidence interval: 1.44-9.81; p =
      0.007). ABCB1 polymorphisms may influence the extent of chemotherapy-induced
      neutropenia in AC combination-treated patients with breast cancer.

PMID- 25989891
TI  - Population pharmacokinetic analysis for 10-monohydroxy derivative of
      oxcarbazepine in pediatric epileptic patients shows no difference between
      Japanese and other ethnicities.
AB  - Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized
      by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD)
      following oral administration. The pharmacokinetic (PK) profiles of MHD were
      evaluated in pediatric epileptic patients and a possible ethnic difference in PK
      of MHD between Japanese and non-Japanese pediatric patients was assessed. A non
      linear mixed effect modeling approach was used to determine the PK of MHD. A one
      compartment population model with first-order absorption appropriately described
      the PK of MHD. No clinically relevant differences were found for using body
      surface area or weight to explain between-patient variability, therefore the
      final model included the effects of body weight on apparent clearance (CL/F) and
      apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3
      concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on
      CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded
      no ethnic difference with respect to CL/F of MHD between Japanese and non
      Japanese patients. Hence, oxcarbazepine can be generally applied using the same
      dosage and administration for the treatment of partial onset seizures in
      pediatric patients, regardless of ethnicity.

PMID- 25989892
TI  - A CAR-responsive enhancer element locating approximately 31 kb upstream in the 5'
      flanking region of rat cytochrome P450 (CYP) 3A1 gene.
AB  - Constitutive androstane receptor (CAR) is one of the principal regulators of
      hepatic cytochrome P450s (CYPs) 3A (CYP3A). cDNA-mediated expression of a mature
      rat CAR (rCAR) into rat hepatoma cells induced CYP3A1 and CYP2B mRNAs. Aberrant
      rCAR failed in these inductions. Three important human CYP3A4 regulatory elements
      (REs), proximal ER6 (proER6), xenobiotic responsive enhancer module (XREM) and
      constitutive liver enhancer module (CLEM), support constitutive and inducible
      expression of CYP3As mediated by CAR and pregnane X receptor (PXR). NHR-scan
      software predicted proER6, XREM and CLEM at -255 b, -8 kb and -11.5 kb,
      respectively of CYP3A4, but neither XREM nor CLEM was predicted in rat CYP3A. A
      luciferase reporter construct carrying a 5'-flanking sequence of CYP3A1 (-31,739
      to -31,585 from its transcription initiation site) revealed important for the
      rCAR-dependent transactivation of CYP3A1. This region includes two putative
      binding motifs of nuclear receptors (DR4 and DR2), a putative hepatocyte nuclear
      factor-1 binding motif (HNF1), nuclear factor-kappa B binding motif (NFkappaB),
      activator protein 1 binding motif (AP-1), and ecotropic viral integration site 1
      binding motif (Evi1). We hereby conclude DR4 and/or DR2 motifs being primarily
      responsible and HNF1 being synergistically functioning elements for the rCAR
      mediated transcription of CYP3A1.

PMID- 25989893
TI  - Dehydroepiandrosterone sulfate, a useful endogenous probe for evaluation of drug
      drug interaction on hepatic organic anion transporting polypeptide (OATP) in
      cynomolgus monkeys.
AB  - Since drug-drug interaction (DDI) can affect organic anion-transporting
      polypeptide (OATP) and cause clinical events, prediction of such DDI is important
      in early clinical development. Although statins are useful probes for OATP
      mediated DDI, endogenous probes would be more practical for predicting such DDI.
      In this study, we investigate the possible use of dehydroepiandrosterone sulfate
      (DHEAS), an endogenous OATP substrate, in predicting OATP-mediated DDI in
      cynomolgus monkeys as a first step toward in human assessment. In in vitro
      experiments, both human and cynomolgus monkey hepatocytes showed a time- and
      temperature-dependent DHEAS uptake. Rifampicin (RIF), a typical OATP inhibitor,
      inhibited this uptake, indicating the involvement of OATP in DHEAS uptake. In in
      vivo experiments, the area under the plasma concentration-time curve (AUC) and
      maximum plasma concentration (Cmax) of DHEAS were significantly increased
      following administration of RIF 10 mg/kg, although the extent of this increase
      was lower than that observed with the test-statins used in this study. However,
      based on the results of in vitro hepatic DHEAS uptake, changes in DHEAS
      concentration are expected to be more prominent in human than in monkey. This
      shows for the first time that DHEAS may be used as endogenous probe for
      predicting OATP-mediated DDI.

PMID- 25989894
TI  - Do All Activities "Weigh" Equally? How Different Physical Activities Differ as
      Predictors of Weight.
AB  - In Britain, it is recommended that, to stay healthy, adults should do 150 minutes
      of moderate-intensity physical activity every week. The recommendations provided
      by the U.K. government, however, remain silent in regard to the type of activity
      that should be done. Using the annual Health Survey for England we compare how
      different types of physical activities predict a person's weight. In particular,
      we consider clinically measured body mass index and waist circumference. We
      document mean slopes emanating from ordinary least squares regressions with these
      measures as the dependent variables. We show that individuals who walk at a brisk
      or fast pace are more likely to have a lower weight when compared to individuals
      doing other activities. Additionally, we highlight that the association between
      physical activity and weight is stronger for females and individuals over the age
      of 50. Our overall conclusions are robust to a number of specifications. 

PMID- 25989895
TI  - Unusual Vascular Complications Associated with Transradial Coronary Procedures
      Among 10,324 Patients: Case Based Experience and Treatment Options.
AB  - OBJECTIVES: We aimed to present our experience regarding the unusual vascular
      complications and specific treatment strategies in patients who underwent
      transradial coronary procedure (TRC). BACKGROUND: Transradial access provides
      lower vascular access site complication rates compared with transfemoral access.
      However, there is lack of data obtained from large study populations concerning
      the incidence and treatment strategies of hemorrhagic and vascular complications
      following a TRC in the literature. METHODS: 10,324 patients (2,652 patients with
      percutaneous coronary intervention and 7,672 patients with a diagnostic
      transradial coronary angiography) who underwent a TRC from February 2010 to
      December 2014 were reviewed to identify cases of large hematoma, perforation,
      arteriovenous fistula, and pseudoaneurysm. RESULTS: The observed incidence was
      0.44% (45 patients) for all unusual vascular and hemorrhagic complications. Of
      these 45 patients; 32 patients (0.31%) presented with large hematoma (>=6 cm), 8
      patients (0.08%) presented with perforation, 4 patients (0.04%) presented with
      arteriovenous fistula (AVF), and only 1 case (0.009%) presented with radial
      artery pseudoaneurysm. Forty-one of forty-five patients were managed with
      mechanical compression. Surgery was performed in only 3 cases; a patient with a
      brachial artery perforation leading to compartment syndrome, a patient with AVF
      resulting in limb ischemia, and a patient with radial artery pseudoaneurysm. A
      right internal mammarian artery perforation resulting in huge breast hematoma was
      treated via endovascular graft stent implantation. CONCLUSIONS: Hemorrhagic and
      vascular complications are rarely seen during TRC. However, majority of these
      complications could be managed conservatively without a requirement for surgical
      reconstruction.

PMID- 25989896
TI  - Efficacy of concomitant use of dexmedetomidine and propofol in tetanus.
AB  - Tetanus is an infectious disease caused by Clostridium tetani, which manifests
      systemic convulsion and autonomic instability associated with high case fatality.
      Despite proper medical intervention, management of those symptoms is often
      difficult. We report a case of 67-year-old man with tetanus in which a
      concomitant use of dexmedetomidine, an adrenaline alpha-2 receptor agonist, and
      propofol, a GABA(A) receptor binding agent, was successful in the management of
      systemic convulsion and autonomic instability without necessitating conventional
      anticonvulsant, neuromuscular blocking agents, or tracheostomy.

PMID- 25989897
TI  - The Effect of Surface Charge Saturation on Heat-induced Aggregation of Firefly
      Luciferase.
AB  - We present here the effect of firefly luciferase surface charge saturation and
      the presence of some additives on its thermal-induced aggregation. Three mutants
      of firefly luciferase prepared by introduction of surface Arg residues named as
      2R, 3R and 5R have two, three and five additional arginine residues substituted
      at their surface compared to native luciferase; respectively. Turbidimetric study
      of heat-induced aggregation indicates that all three mutants were reproducibly
      aggregated at higher rates relative to wild type in spite of their higher
      thermostability. Among them, 2R had most evaluated propensity to heat-induced
      aggregation. Therefore, the hydrophilization followed by appearing of more
      substituted arginine residues with positive charge on the firefly luciferase
      surface was not reduced its thermal aggregation. Nevertheless, at the same
      condition in the presence of charged amino acids, e.g. Arg, Lys and Glu, as well
      as a hydrophobic amino acid, e.g. Val, the heat-induced aggregation of wild type
      and mutants of firefly luciferases was markedly decelerated than those in the
      absence of additives. On the basis of obtained results it seems, relinquishment
      of variety in charge of amino acid side chains, they via local interactions with
      proteins cause to decrease rate and extent of their thermal aggregation. 

PMID- 25989898
TI  - Repairing organs: lessons from intestine and liver.
AB  - The concept of organ regeneration has fascinated humanity from ancient mythology
      to modern science fiction. Recent advances offer the potential to soon bring such
      technology within the grasp of clinical medicine. Rapidly expanding insights into
      the intrinsic repair processes of the intestine and liver have uncovered
      significant plasticity in epithelial tissues. Harnessing this knowledge,
      researchers have recently created culture systems that enable the expansion of
      stem cells into transplantable tissue in vitro. Here we discuss how the growing
      tool set of stem cell biology can bring organ repair from fictitious narrative to
      medical practice. 

PMID- 25989899
TI  - Modifiable and non-modifiable factors associated with employment outcomes
      following spinal cord injury: A systematic review.
AB  - CONTEXT: Employment rates in individuals with spinal cord injury (SCI) are
      approximately 35%, which is considerably lower than that of the general
      population. In order to improve employment outcomes a clear understanding of what
      factors influence employment outcomes is needed. OBJECTIVE: To systematically
      review factors that are consistently and independently associated with employment
      outcomes in individuals with SCI, and to understand the magnitude of their
      influence. METHODS: Through an electronic search of MEDLINE/PubMed, EMBASE,
      CINAHL, PsycINFO, Social Science Abstracts and Social Work databases, we
      identified studies published between 1952-2014 that investigated factors
      associated with employment outcomes following SCI. Exclusion criteria included:
      (1) reviews (2) studies not published in English (3) studies not controlling for
      potential confounders through a regression analysis, or (4) studies not providing
      an effect measure in the form of OR, RR, or HR. Data were categorized based on
      the International Classification of Functioning, Disability and Health framework,
      with each domain sub-categorized by modifiability. First author, year of
      publication, sample size, explanatory and outcome variables, and effect measures
      were extracted. RESULTS: Thirty-nine studies met the inclusion criteria. Twenty
      modifiable and twelve non-modifiable factors have been investigated in the
      context of employment following SCI. Education, vocational rehabilitation,
      functional independence, social support, and financial disincentives were
      modifiable factors that have been consistently and independently associated with
      employment outcomes. CONCLUSION: A number of key modifiable factors have been
      identified and can inform interventions aimed at improving employment outcomes
      for individuals with SCI. Future research should focus on determining which
      factors have the greatest effect on employment outcomes, in addition to
      developing and evaluating interventions targeted at these factors.

PMID- 25989900
TI  - Erratum to: Extensive multifocal branch duct IPMN of the pancreas after liver
      transplantation: is surgery justified?

PMID- 25989901
TI  - Evolutionary relationships of West Nile virus detected in mosquitoes from a
      migratory bird zone of Colombian Caribbean.
AB  - BACKGROUND: West Nile virus (WNV) is a member of the genus Flavivirus, and it is
      transmitted between Culex sp. mosquitoes and avian hosts. Equids and humans are
      commonly infected with WNV as dead-end hosts, and the signs and symptoms of
      infection range from mild illness to neurologic symptoms as encephalitis,
      meningitis and sometimes death. Previous phylogenetic studies have classified WNV
      into six genetically distinct lineages and provided valuable insight on WNV
      dispersal patterns within the Americas and its emergence in different geographic
      areas. In this study, we isolated, sequenced and genetically characterized the
      NS5 and envelope genes for two WNV strains detected from Northern of Colombia.
      Herein we describe the evolutionary relationships with representative WNV-strains
      isolated in a variety of epidemic outbreaks and countries, to define the
      phylogeographic origin and possible implications in the epidemiology of this
      emergent virus in Colombia. FINDINGS: Fragments of the NS5 and Envelope genes
      were amplified with RT-PCR and sequenced to obtain 1186-nt and 1504-nt portions,
      respectively. Our sequences were aligned with 46 sequences from WNV-strains
      collected in the U.S., Mexico and Argentina for phylogenetic reconstruction using
      Bayesian methods. Sequence analyses identified unique non-synonymous
      substitutions in the envelope gene of the WNV strains we detected, and our
      sequences clustered together with those from the attenuated Texas - 2002
      genotype. CONCLUSIONS: A new strain closely related to attenuated strains
      collected in Texas during 2002 was identified from Colombia by phylogenetic
      analysis. This finding may explain the absence of human/equine cases of WNV
      encephalitis or severe disease in Colombia and possibly other regions of South
      America. Follow-up studies are needed in ecosystems used by migratory birds areas
      and virological/entomological surveillance.

PMID- 25989902
TI  - Tamoxifen use reduces the risk of osteoporotic fractures in women with breast
      cancer in Asia: a nationwide population-based cohort study.
AB  - PURPOSE: Bone mineral density changes with tamoxifen treatment have been reported
      in pre- and post-menopausal women with breast cancer. However, there remains
      controversy as to whether tamoxifen significantly reduces fracture rates in
      different age groups. Breast cancer occurs at 10-20 years younger in Asian women
      compared with Western women. Therefore we conducted this population-based case
      control study to determine whether or not tamoxifen use is associated with
      osteoporotic fractures. PATIENTS AND METHODS: We selected 75488 women with breast
      cancer with no prior history of fractures from the Longitudinal Health Insurance
      Database for Catastrophic Illness Patients in 2000-2011. They were followed from
      the date of the diagnosis of breast cancer to the date a hip, vertebral or wrist
      fracture occurred. Because the use of tamoxifen was a time-dependent variable, we
      used a Cox proportional hazard model with time-dependent exposure covariates to
      estimate the risk of a fracture. RESULTS: There were 50257 and 25231 women with
      breast cancer who did and did not receive tamoxifen treatment, respectively. The
      tamoxifen users had lower risks for overall fractures with hazard ratios (HRs) of
      0.52 and 0.59 in the crude and adjusted models (95 % CI = 0.45-0.61 and 0.51
      0.69), respectively. They also had lower risks for hip (HR = 0.55, 95 % CI = 0.45
      0.67) and vertebral (HR = 0.64, 95 % CI = 0.50-0.82) fractures in the adjusted
      model. The risk of fractures decreased with an increasing dosage of tamoxifen.
      Regardless of the age group, the tamoxifen users had a lower risk of fractures
      than the non-users. CONCLUSION: In this Asian population-based case-control
      study, tamoxifen use was associated with a reduction in osteoporotic fractures,
      especially in hip fractures.

PMID- 25989903
TI  - The fission yeast MTREC complex targets CUTs and unspliced pre-mRNAs to the
      nuclear exosome.
AB  - Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome.
      However, the mechanism by which they are recognized and targeted to the exosome
      is not fully understood. Here we report that the MTREC complex, which has
      recently been shown to promote degradation of meiotic mRNAs and regulatory
      ncRNAs, is also the major nuclear exosome targeting complex for CUTs and
      unspliced pre-mRNAs in Schizosaccharomyces pombe. The MTREC complex specifically
      binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these
      RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a
      minor role in this process. The MTREC complex physically interacts with the
      nuclear exosome and with various RNA-binding and RNA-processing complexes,
      coupling RNA processing to the RNA degradation machinery. Our study reveals the
      central role of the evolutionarily conserved MTREC complex in RNA quality
      control, and in the recognition and elimination of CUTs. 

PMID- 25989905
TI  - Estimation of genetic parameters and detection of quantitative trait loci for
      minerals in Danish Holstein and Danish Jersey milk.
AB  - BACKGROUND: Bovine milk provides important minerals, essential for human
      nutrition and dairy product quality. For changing the mineral composition of the
      milk to improve dietary needs in human nutrition and technological properties of
      milk, a thorough understanding of the genetics underlying milk mineral contents
      is important. Therefore the aim of this study was to 1) estimate the genetic
      parameters for individual minerals in Danish Holstein (DH) (n=371) and Danish
      Jersey (DJ) (n=321) milk, and 2) detect genomic regions associated with mineral
      content in the milk using a genome-wide association study (GWAS) approach.
      RESULTS: For DH, high heritabilities were found for Ca (0.72), Zn (0.49), and P
      (0.46), while for DJ, high heritabilities were found for Ca (0.63), Zn (0.57),
      and Mg (0.57). Furthermore, intermediate heritabilities were found for Cu in DH,
      and for K, Na, P and Se in the DJ. The GWAS revealed a total of 649 significant
      SNP markers detected for Ca (24), Cu (90), Fe (111), Mn (3), Na (1), P (4), Se
      (12) and Zn (404) in DH, while for DJ, a total of 787 significant SNP markers
      were detected for Ca (44), Fe (43), K (498), Na (4), Mg (1), P (94) and Zn (3).
      Comparing the list of significant markers between DH and DJ revealed that the SNP
      ARS-BFGL-NGS-4939 was common in both breeds for Zn. This SNP marker is closely
      linked to the DGAT1 gene. Even though we found significant SNP markers on BTA14
      in both DH and DJ for Ca, and Fe these significant SNPs did not overlap.
      CONCLUSION: The results show that Ca, Zn, P and Mg show high heritabilities. In
      combination with the GWAS results this opens up possibilities to select for
      specific minerals in bovine milk.

PMID- 25989907
TI  - How electrodiagnosis predicts clinical outcome of focal peripheral nerve lesions.
AB  - This article reviews the electrodiagnostic (EDX) prognostic factors for focal
      traumatic and nontraumatic peripheral nerve injuries. Referring physicians and
      patients often benefit from general and nerve-specific prognostic information
      from the EDX consultant. Knowing the probable outcome from a nerve injury allows
      the referring physician to choose the best treatment options for his/her
      patients. Nerve injuries are variable in their mechanism, location, and
      pathophysiology. The general effects of the injuries on nerve and muscle are well
      known, but more research is needed for nerve-specific information. Several
      factors currently known to influence prognosis include: nature of the nerve
      trauma, amount of axon loss, recruitment in muscles supplied by the nerve, the
      extent of demyelination, and the distance to reinnervate functional muscles. This
      article reviews these general concepts and also nerve-specific EDX measures that
      predict outcome after focal neuropathies.

PMID- 25989904
TI  - Parallel transmission for ultrahigh-field imaging.
AB  - The development of MRI systems operating at or above 7 T has provided researchers
      with a new window into the human body, yielding improved imaging speed,
      resolution and signal-to-noise ratio. In order to fully realise the potential of
      ultrahigh-field MRI, a range of technical hurdles must be overcome. The non
      uniformity of the transmit field is one of such issues, as it leads to non
      uniform images with spatially varying contrast. Parallel transmission (i.e. the
      use of multiple independent transmission channels) provides previously
      unavailable degrees of freedom that allow full spatial and temporal control of
      the radiofrequency (RF) fields. This review discusses the many ways in which
      these degrees of freedom can be used, ranging from making more uniform transmit
      fields to the design of subject-tailored RF pulses for both uniform excitation
      and spatial selection, and also the control of the specific absorption rate. (c)
      2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

PMID- 25989910
TI  - Novel Inflammatory Markers in Hyperlipidemia: Clinical Implications.
AB  - Hyperlipidemia is characterized by abnormally increased plasma of any or all
      lipids and /or lipoproteins and is a confirmed risk factor for the formation of
      atherosclerosis. Inflammation plays a crucial role in the formation and
      progression of atherosclerosis and consequently on cardiovascular diseases.
      Nowadays, the effective role of the immune system and subsequently of systemic
      inflammation is well established. Multiple levels of evidence from experimental
      models and histopathologic assessment of tissues to systemic biomarkers and
      epidemiologic or clinical associations have revealed that inflammation is one of
      the basic mechanisms in the destabilization of the atherogenetic plaque which
      leads to clinical events. Several inflammatory markers are affiliated with lipids
      level and the process of atherosclerosis. The most known of them are interleukin
      6 and interleukin 1beta, C-reactive protein, tumor necrosis factor-alpha,
      pentraxin3, serum amyloid A, sCD40, adhesion molecules, monocyte chemoattractant
      protein-1, sEndoglin, PAPP-A, chemokine 16, insulin like growth factor,
      lipoprotein-associated phospholipase A2 and galectin 3 but their role in
      atherogenesis is not well established for all of them. As atheromatosis is one of
      the main causes of death all over the world, in upcoming studies it will be
      useful to specify the exact role of these markers in this process in order to
      have a better prognosis, diagnosis and understanding of this disorder. The aim in
      this review is to study the literature on the novel inflammation markers of
      hyperlipidemia according to their clinical implications. 

PMID- 25989906
TI  - Determinants of hydroxychloroquine blood concentration variations in systemic
      lupus erythematosus.
AB  - OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among
      patients with systemic lupus erythematosus (SLE). A
      pharmacokinetic/pharmacodynamic relationship has been found in different
      situations, and a very low blood concentration of HCQ is a simple marker of
      nonadherence to treatment. Therefore, interest in blood HCQ concentration
      measurement has increased, but little is known about factors that influence blood
      HCQ concentration variability. This study was undertaken to analyze determinants
      of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of
      patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to
      determine the association of epidemiologic, clinical, and biologic factors with
      blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration
      <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we
      restricted the analyses of the PLUS data to the 509 SLE patients receiving 400
      mg/day. We found no association of ethnicity or smoking with blood HCQ
      concentrations and no pharmacokinetic drug-drug interaction with antacids or with
      inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high
      body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04),
      increased time between the last tablet intake and measurement of blood HCQ
      concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count
      (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated
      with low blood HCQ concentrations. In 22 SLE patients with chronic renal
      insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58
      ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was
      significantly higher than that in the 509 patients from the PLUS study (1,338
      ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P <
      0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood
      HCQ concentrations. Because this measurement is increasingly being used, these
      data might be useful for clinicians.

PMID- 25989908
TI  - Physical activity level is not a determinant of autonomic nervous system activity
      and clinical severity in children/adolescents with sickle cell anemia: A pilot
      study.
AB  - BACKGROUND: Autonomic nervous system (ANS) activity has been suggested to
      modulate the clinical severity of sickle cell anemia (SCA) by increasing the risk
      for vaso-occlusive events. Regular physical activity (PA) is known to improve ANS
      activity and health status in several cardiovascular and metabolic diseases.
      Whether regular PA improves the health status of SCA patients remains unknown.
      PROCEDURE: Twenty-two patients with SCA and 15 healthy (AA) children/adolescents
      participated to the study. Heart rate variability was measured in supine position
      and after a tilt-test to quantify the ANS activity. PA energy expenditure (PAEE)
      was assessed with questionnaire. RESULTS: 1) PAEE was lower in SCA compared to AA
      (190 +/- 152 vs. 432 +/- 277 kcal . d(-1), respectively, P < 0.01), 2) overall
      ANS activity was lower in SCA compared to AA, 3) parasympathetic withdrawal was
      observed in SCA with aging, 4) ANS reactivity was slightly impaired in SCA
      compared to AA (reduction in HFnu: -38 +/- 27 vs. -58 +/- 14%, respectively, P <
      0.05), 5) ANS indices, PAEE, and rates of clinical events were not correlated.
      CONCLUSION: Both the level of PA and ANS activity are reduced in SCA compared to
      AA children/adolescents, particularly in those older than 15 years. Neither PAEE,
      nor ANS activity seem to influence the clinical severity of children/adolescents
      with SCA.

PMID- 25989911
TI  - Therapeutic Effects of Herbal Chemicals in Traditional Chinese Medicine on
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common type of dementia that leads to
      increasing death and mental disability among humans. Current therapy of AD mainly
      relies on the use of acetylcholinesterase inhibitors (AChEIs) or antagonists of N
      methyl-D-aspartate receptors (NMDARs), which only relieve the symptoms of the
      disease but not halt its progression. Nevertheless, Traditional Chinese medicines
      (TCM) are highly prized as many bioactive components isolated from TCM are
      beneficial for treating AD. In this review, we summarize the latest information
      on TCM and the bioactive components according to their mechanistic role in
      alleviating AD. They act as modulators of alpha- and beta-secretases, and
      inhibitors of betaamyloid (Abeta) aggregation. Some of them suppress Abeta
      induced neuronal cytotoxicity and inflammation. Hence, this work has demonstrated
      the feasibility of applying TCM in AD therapy and the possibility of screening of
      constituents in TCM in the near future. 

PMID- 25989913
TI  - Erratum to: Acute response test to adaptive servo-ventilation, a possible
      modality to assessing the reversibility of pulmonary vascular resistance.

PMID- 25989912
TI  - Non-traditional systemic treatments for diabetic retinopathy: an evidence-based
      review.
AB  - The rapid escalation in the global prevalence diabetes, with more than 30% being
      afflicted with diabetic retinopathy (DR), means it is likely that associated
      vision-threatening conditions will also rise substantially. This means that new
      therapeutic approaches need to be found that go beyond the current standards of
      diabetic care, and which are effective in the early stages of the disease. In
      recent decades several new pharmacological agents have been investigated for
      their effectiveness in preventing the appearance and progression of DR or in
      reversing DR; some with limited success while others appear promising. This up-to
      date critical review of non-traditional systemic treatments for DR is based on
      the published evidence in MEDLINE spanning 1980-December 2014. It discusses a
      number of therapeutic options, paying particular attention to the mechanisms of
      action and the clinical evidence for the use of renin-angiotensin system
      blockade, fenofibrate and calcium dobesilate monohydrate in DR. 

PMID- 25989915
TI  - Solution-Grown Nanowire Devices for Sensitive and Fast Photodetection.
AB  - Highly sensitive and fast photodetector devices with CdSe quantum nanowires as
      active elements have been developed exploiting the advantages of electro- and wet
      chemical routes. Bismuth nanoparticles electrochemically synthesized directly
      onto interdigitating platinum electrodes serve as catalysts in the following
      solution-liquid-solid synthesis of quantum nanowires directly on immersed
      substrates under mild conditions at low temperature. This fast and simple
      preparation process leads to a photodetector device with a film of nanowires of
      limited thickness bridging the electrode gaps, in which a high fraction of
      individual nanowires are electrically contacted and can be exposed to light at
      the same time. The high sensitivity of the photodetector device can be expressed
      by its on/off ratio or its photosensitivity of more than 10(7) over a broad
      wavelength range up to about 700 nm. The specific detectivity and responsivity
      are determined to D* = 4 * 10(13) Jones and R = 0.32 A/W, respectively. The speed
      of the device reflects itself in a 3 dB frequency above 1 MHz corresponding to
      rise and fall times below 350 ns. The remarkable combination of a high
      sensitivity and a fast response is attributed to depletion regions inside the
      nanowires, tunnel-junction barriers between nanowires, and Schottky contacts at
      the electrodes, where all of these features are strongly influenced by the number
      of photogenerated charge carriers. 

PMID- 25989914
TI  - Family history and outcome of young patients with breast cancer in the UK (POSH
      study).
AB  - BACKGROUND: Young patients presenting to surgical clinics with breast cancer are
      usually aware of their family history and frequently believe that a positive
      family history may adversely affect their prognosis. Tumour pathology and
      outcomes were compared in young British patients with breast cancer with and
      without a family history of breast cancer. METHODS: Prospective Outcomes in
      Sporadic versus Hereditary breast cancer (POSH) is a large prospective cohort
      study of women aged less than 41 years with breast cancer diagnosed and treated
      in the UK using modern oncological management. Personal characteristics, tumour
      pathology, treatment and family history of breast/ovarian cancer were recorded.
      Follow-up data were collected annually. RESULTS: Family history data were
      available for 2850 patients. No family history was reported by 65.9 per cent, and
      34.1 per cent reported breast/ovarian cancer in at least one first- or second
      degree relative. Patients with a family history were more likely to have grade 3
      tumours (63.3 versus 58.9 per cent) and less likely to have human epidermal
      growth factor receptor 2-positive tumours (24.7 versus 28.8 per cent) than those
      with no family history. In multivariable analyses, there were no significant
      differences in distant disease-free intervals for patients with versus those
      without a family history, either for the whole cohort (hazard ratio (HR) 0.89, 95
      per cent c.i. 0.76 to 1.03; P = 0.120) or when stratified by oestrogen receptor
      (ER) status (ER-negative: HR 0.80, 0.62 to 1.04, P = 0.101; ER-positive: HR 0.95,
      0.78 to 1.15, P = 0.589). CONCLUSION: Young British patients presenting to breast
      surgical clinics with a positive family history can be reassured that this is not
      a significant independent risk factor for breast cancer outcome.

PMID- 25989916
TI  - Gender differences in outpatients with anxiety disorders: the Leiden Routine
      Outcome Monitoring Study.
AB  - BACKGROUND: Data from the general population show higher prevalence of different
      anxiety disorders in women as compared with men. We analysed gender differences
      in a naturalistic sample of outpatients with anxiety disorders in a mental
      healthcare setting. METHOD: Routine outcome monitoring data were collected from
      1333 patients (age: 18-65; 63.3% women) fulfilling Diagnostic and Statistical
      Manual of Mental Disorders IV criteria of current anxiety disorder according to
      the Mini-International Neuropsychiatric Interview between 2004 through 2006. Data
      included Comprehensive Psychopathological Rating Scale, Brief Symptom Inventory
      (BSI), Short Form Health Survey (SF-36), Mood and Anxiety Symptom Questionnaire
      (MASQ). Chi-squared test and t-test were used to compare women with men for
      variables with parametric distributions, and Mann-Whitney test for non-parametric
      distribution. Adjustments for potential confounders (age, level of education,
      ethnicity and comorbidites) were made by logistic regression models (for discrete
      variables) or analysis of covariance. RESULTS: The female-to-male ratio (i.e.,
      844 women, 489 men) for any anxiety disorder was 1.73 : 1 (95% confidence
      interval [CI]: 1.63-1.83), with the strongest skewness for post-traumatic stress
      disorder (2.80 : 1) and the smallest one for social phobia (1.18 : 1). Compared
      with men, women reported more severe self-rating scores on the BSI (on average,
      the scores were 12.3% higher on 3 of 9 subscales: somatisation, interpersonal
      sensitivity and anxiety), SF-36 (self-reported generic health status was lower on
      5 of 8 subscales: physical functioning, social functioning, physical problems,
      vitality and bodily pain) and MASQ (on average, the scores were 6.6% higher on 4
      of 5 subscales: anxious arousal, general distress, general distress depression,
      general distress anxiety). On the contrary, no gender difference was found in the
      severity of anxiety symptoms measured by the Brief Anxiety Scale. Women were more
      likely to suffer from comorbid depression and bulimia nervosa, and less likely
      from substance abuse. CONCLUSIONS: In a treatment-seeking population the
      prevalence rate of anxiety disorders was 1.7 times higher in female compared with
      men. Female outpatients were more severely affected on self-rated but not on
      observer-rated scales.

PMID- 25989917
TI  - Infratrochlear nerve block for a new infratrochlear neuralgia.

PMID- 25989918
TI  - Survival and Elimination of Hepatitis E Virus: A Review.
AB  - Recently, foodborne transmission of hepatitis E virus (HEV) has become a concern
      due to the identification of undercooked pork products as a risk factor for
      infection. The limited number of studies which have been performed indicate that
      HEV could remain infectious at temperatures used in some cooking regimes,
      although inactivation by heating at 71  degrees C for 20 min has been
      demonstrated. There are significant gaps in our knowledge regarding the survival
      of HEV in foods and the environment (including food contact surfaces), and also
      regarding the effect of elimination procedures used in food supply chain
      settings. The lack of a reliable infectivity assay has hampered extensive study.
      It is recommended that studies be undertaken to develop an efficient propagation
      system (based on in vitro cell culture), to facilitate the acquisition of
      extensive information on the survival of HEV in food and the environment, and its
      response to disinfection and elimination procedures.

PMID- 25989919
TI  - Prejudice in reports on misconduct cases in The BMJ.

PMID- 25989920
TI  - MEDICAL DEVICE PRICES IN ECONOMIC EVALUATIONS.
AB  - OBJECTIVES: Economic evaluations, although not formally used in purchasing
      decisions for medical devices in Canada, are still being conducted and published.
      The aim of this study was to examine the way that prices have been included in
      Canadian economic evaluations of medical devices. METHODS: We conducted a review
      of the economic concepts and implications of methods used for economic
      evaluations of the eleven most implanted medical devices from the Canadian
      perspective. RESULTS: We found Canadian economic studies for five of the eleven
      medical devices and identified nineteen Canadian studies. Overall, the device
      costs were important components of total procedure cost, with an average ratio of
      44.1 %. Observational estimates of the device costs were obtained from buyers or
      sellers in 13 of the 19 studies. Although most of the devices last more than 1
      year, standard costing methods for capital equipment was never used. In addition,
      only eight studies included a sensitivity analysis for the device cost. None of
      the sensitivity analyses were based on actual price distributions. CONCLUSIONS:
      Economic evaluations are potentially important for policy making, but although
      they are being conducted, there is no standardized approach for incorporating
      medical device prices in economic analyses. Our review provides suggestions for
      improvements in how the prices are incorporated for economic evaluations of
      medical devices.

PMID- 25989921
TI  - Experimental pig-to-pig transmission dynamics for African swine fever virus,
      Georgia 2007/1 strain.
AB  - African swine fever virus (ASFV) continues to cause outbreaks in domestic pigs
      and wild boar in Eastern European countries. To gain insights into its
      transmission dynamics, we estimated the pig-to-pig basic reproduction number (R
      0) for the Georgia 2007/1 ASFV strain using a stochastic susceptible-exposed
      infectious-recovered (SEIR) model with parameters estimated from transmission
      experiments. Models showed that R 0 is 2.8 [95% confidence interval (CI) 1.3-4.8]
      within a pen and 1.4 (95% CI 0.6-2.4) between pens. The results furthermore
      suggest that ASFV genome detection in oronasal samples is an effective diagnostic
      tool for early detection of infection. This study provides quantitative
      information on transmission parameters for ASFV in domestic pigs, which are
      required to more effectively assess the potential impact of strategies for the
      control of between-farm epidemic spread in European countries.

PMID- 25989922
TI  - Is liver stiffness measurement to stage fibrosis in patients with nonalcoholic
      fatty liver disease ready for clinical use?

PMID- 25989923
TI  - A comparison of two approaches to training visual analysis of AB graphs.
AB  - Visual analysis is the primary method of evaluating data in single-subject
      research. Few studies have evaluated interventions to teach visual analys is
      skills. The purpose of this study was to evaluate systematic instruction,
      delivered using computer-based intervention or a recorded lecture, on identifying
      changes in slope and level in AB graphs. Results indicated that both approaches
      were significantly more effective than a no-treatment control condition but were
      not different from each other. We discuss the implications of these results for
      training and directions for future research. 

PMID- 25989924
TI  - Co-adjuvant effects of plant polysaccharide and propolis on chickens inoculated
      with Bordetella avium inactivated vaccine.
AB  - Taishan Pinus massoniana pollen polysaccharide (TPPPS), propolis (PP) and aloe
      polysaccharide (AP), used as adjuvants, have been proven to possess immunity
      enhancing functions. However, their collaborative immunomodulatory effects are
      largely unknown. To determine which combination can induce the best effects, the
      three adjuvants were separately or conjointly added into Bordetella avium
      inactivated vaccines to investigate their co-adjuvant effects on vaccinated
      chickens. We found that, among all six adjuvant-treated vaccine inoculated groups
      (TPPPS, PP, AP, TPPPS-PP, PP-AP and TPPPS-AP), the chickens inoculated with
      TPPPS, PP or TPPPS-PP adjuvant vaccines showed significantly higher levels of
      antibody titre, cytokine, lymphocyte transformation and peripheral blood T
      lymphocyte count than those of non-adjuvant vaccine inoculated groups (P < 0.05),
      indicating the good immune-enhancing effects of TPPPS and PP. The TPPPS-PP group
      showed the highest levels of antibody titres and interleukin-2 (IL-2) at 14-28
      days post the first inoculation (dpi), lymphocyte transformation rates (LTRs) at
      14-35 dpi, CD4(+) T-lymphocyte counts at 14-42 dpi, and CD8(+) T-lymphocyte
      counts at 28 dpi. The results revealed that B. avium inactivated vaccine used
      conjointly with TPPPS and PP induced the strongest humoral and cellular immune
      responses. Thus, there was a synergistic effect between TPPPS and PP on enhancing
      immunity, which suggests that they can be used as a novel adjuvant formulation
      for the development of poultry vaccines. 

PMID- 25989925
TI  - Diabetic polyneuropathy and the risk of developing diabetic retinopathy: a
      nationwide, population-based study.
AB  - PURPOSE: To assess the relationship between diabetic polyneuropathy (DPN) and the
      risk of diabetic retinopathy (DR). METHODS: From 1997 to 2010, we identified 5031
      newly diagnosed DPN patients and 20 124 controls matched for sex, age, and index
      year. Cox proportional hazards regression analyses were used to estimate the
      adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of DR between the
      DPN patients and the non-DPN group. The adjusted hazard ratio was calculated and
      adjusted for age, sex, duration of diabetes and comorbidities of hypertension,
      cardiovascular disease and diabetic nephropathy. RESULTS: The incidence rate of
      DR was 5.87-fold higher in the DPN patients than in the non-DPN group (44.0 vs.
      7.22 per 1000 person-years), with an adjusted HR of 5.41(95% CI = 4.92-5.94). The
      DPN-to-non-DPN DR incidence rate ratio decreased with age (adjusted HR = 6.63 for
      subgroup younger than 65 years and adjusted HR = 3.91 for subgroup aged 65 years
      or older). Compared with the non-DPN group, the DPN patients had a 5.63-fold risk
      of non-proliferative DR (adjusted HR = 5.63, 95% CI = 5.11-6.21) and a 3.67-fold
      risk of proliferative DR (adjusted HR = 3.67, 95% CI = 2.57-5.23). CONCLUSION:
      The patients with DPN had an increased risk of developing DR and advanced DR
      compared with the non-DPN group, particularly among the subgroup aged younger
      than 65 years.

PMID- 25989926
TI  - Fecal microRNA profile in patients with colorectal carcinoma before and after
      curative surgery.
AB  - PURPOSE: The purpose of this study was to explore the potential role of deranged
      fecal microRNA (miRNA) pattern as a reliable warning signal of colorectal cancer
      (CRC), a subset of fecal CRC-related miRNAs was evaluated in CRC patients, before
      and after surgery, and in healthy controls. METHODS: Twenty CRC patients and 20
      age/sex-matched healthy volunteers with negative colonoscopy entered the study.
      Cancer biopsy, colonic mucosa from the resected specimens, and fecal samples from
      patients and controls were screened for 13 miRNAs involved in CRC onset and
      progressions by reverse transcription quantitative PCR (RT-qPCR). Postoperative
      evaluation of fecal miRNAs was carried out after a median follow-up of 18 months
      (range 12-30). RESULTS: Two out 13 miRNAs (RNU6B, miR-16-3p) were used as
      internal controls leaving 11 available for analysis. Cancer tissue contained
      significantly higher expression of all miRNAs, compared to normal mucosa (p <
      0.05). Expression of preoperative levels of five fecal miRNAs, (miR-19-b-3p, miR
      20a-5p, miR-21-3p, miR92a-3p, miR141) was significantly higher in CRC patients
      compared to controls and significantly decreased after curative surgery. Three
      out of these five miRNAs (miR20a-5p, miR21-3p, and miR141) returned to values
      comparable to normal controls. CONCLUSIONS: A set of three specific fecal miRNAs
      is overexpressed before surgery, and return within the normal range after cancer
      removal could be considered as an appealing opportunity for a new reliable tool
      for CRC secondary prevention. However, their role needs to be explored in large
      prospective trials and compared with the existing screening tools.

PMID- 25989927
TI  - Surgical options for locally recurrent rectal cancer--review and update.
AB  - Locally recurrent rectal tumours in the pelvis are found in about 6% following
      treatment for rectal cancer. This type of tumour can cause serious local
      complications and symptoms. The aim of modern surgical oncology is to offer a
      curative treatment option embedded in an interdisciplinary network of
      specialities to the patient. Due to advancements in surgical techniques and
      procedures, especially regarding surgical reconstruction, the possibilities of a
      curative treatment regarding recurrent cancers have been expanded and
      established. To aim for a curative treatment one must introduce a multimodal
      therapy including radio- and chemotherapy, and a radical oncological surgery with
      en bloc resection of the tumour and affected surrounding organs to achieve a R0
      resection.

PMID- 25989928
TI  - Waste not, want more: a call for surgeons to support the manufacture of non-cross
      linked biologic grafts specifically sized for laparoscopic ventral rectopexy.

PMID- 25989929
TI  - Compression anastomotic ring-locking procedure (CARP) is a safe and effective
      method for intestinal anastomoses following left-sided colonic resection.
AB  - BACKGROUND: Compression anastomotic ring-locking procedure (CARP) is a novel
      procedure for creating colonic anastomoses. The surgical procedure allows
      perioperative quantification of the compression pressure between the intestinal
      ends within the anastomosis and postoperative monitoring of the anastomotic
      integrity. We have recently shown that CARP is a safe and effective method for
      colonic anastomoses in pigs, and the purpose of the present study was to evaluate
      CARP for colonic anastomoses in humans. MATERIALS AND METHODS: This is a
      prospective study on 25 patients undergoing elective left-sided colonic
      resection. Time for evacuation of the anastomotic rings, perioperative
      compression pressure, and adverse effects were recorded. Postoperative blood
      samples were collected daily, and flexible sigmoidoscopy was performed 8-12 weeks
      after surgery to examine the anastomoses. RESULTS: Fourteen out of 25 patients
      underwent CARP. CARP was not used in 11 patients due to advanced tumor disease
      (two cases) and size restrictions (nine cases). No case of anastomotic leakage,
      bowel obstruction, or stenosis formation was observed. No device-related
      perioperative adverse events were noted. The surgical device evacuated
      spontaneously in all patients by the natural route after a median of 10 days.
      Perioperative compression pressure ranged between 85 and 280 mBar (median 130
      mBar). Flexible sigmoidoscopy revealed smooth anastomoses without signs of
      pathological inflammation or stenosis in all cases. CONCLUSION: Our results
      indicate that the novel suture-less CARP is a safe and effective method for
      creating colonic anastomoses. Further studies are warranted in larger patient
      populations to compare CARP head-on-head with stapled and/or hand-sewn colonic
      anastomoses.

PMID- 25989930
TI  - Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a
      prospective study.
AB  - PURPOSE: The aim of this study was to evaluate outpatient, non-antibiotic
      management in acute uncomplicated diverticulitis with regard to admissions,
      complications, and recurrences, within a 3-month follow-up period. METHODS: A
      prospective, observational study in which patients with computer tomography
      verified acute uncomplicated diverticulitis were managed as outpatients without
      antibiotics. The patients kept a personal journal, were contacted daily by a
      nurse, and then followed up by a surgeon at 1 week and 3 months. RESULTS: In
      total, 155 patients were included, of which 54 were men; the mean age of the
      patients was 57.4 years. At the time of diagnosis, the mean C-reactive protein
      and white blood cell count were 73 mg/l and 10.5 * 10(9), respectively, and
      normalized in the vast majority of patients within the first week. The majority
      of the patients (97.4%) were managed successfully as outpatients without
      antibiotics, admissions, or complications. In only four (2.6%) patients, the
      management failed because of complications in three and deterioration in one.
      These patients were all treated successfully as inpatients without surgery. Five
      patients had recurrences and were treated as outpatients without antibiotics.
      Follow-up colonic investigations revealed cancer in two patients and polyps in 13
      patients. CONCLUSION: Previous results of low complication rates with the non
      antibiotic policy were confirmed. The new policy of outpatient management without
      antibiotics in acute uncomplicated diverticulitis is now shown to be feasible,
      well functioning, and safe.

PMID- 25989931
TI  - Percutaneous cryoablation of renal masses under CT fluoroscopy: radiation doses
      to the patient and interventionalist.
AB  - PURPOSE: Computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation
      is an effective therapeutic method used to treat focal renal masses. The purpose
      of this study is to quantify the radiation dose to the patient and interventional
      radiologist during percutaneous cryoablation of renal masses using CT
      fluoroscopic guidance. METHODS: Over a 1-year period, the CT fluoroscopy time
      during percutaneous cryoablation of renal masses was recorded in 41 patients. The
      level of complexity of each procedure was designated as simple, intermediate, or
      complex. Patient organ radiation doses were estimated using an anthropomorphic
      model. Dose to the interventional radiologist was estimated using ion chamber
      survey meters. RESULTS: The average CT fluoroscopy time for technically simple
      cases was 47 s, 126 s for intermediate cases, and 264 s for complex cases. The
      relative risk of hematologic stomach and liver malignancy in patients undergoing
      this procedure was 1.003-1.074. The lifetime attributable risk of cancer ranged
      from 2 to 58, with the highest risk in younger patients for developing leukemia.
      The estimated radiation dose to the interventionalist without lead shielding was
      390 mR (3.9 mGy) per year of cases. CONCLUSIONS: The radiation risk to the
      patient during CT fluoroscopy-guided percutaneous renal mass cryoablation is, as
      expected, related to procedure complexity. Quantification of patient organ
      radiation dose was estimated using an anthropomorphic model. This information,
      along with the associated relative risk of malignancy, may assist in evaluating
      risks of the procedure, particularly in younger patients. The radiation dose to
      the interventionist is low regardless of procedure complexity, but highlights the
      importance of lead shielding.

PMID- 25989932
TI  - Non-hyperfunctioning pancreatic endocrine tumors: multimodality imaging features
      with histopathological correlation.
AB  - PURPOSE: To evaluate the multimodality imaging features of non-hyperfunctioning
      pancreatic endocrine tumors (NF-PNET) with histopathological correlation.
      METHODS: Preoperative imaging (CT: n = 23; MRI: n = 14; (111)In-octreotide: n =
      8) of 28 patients (17 female; mean age 55 years) with resected NF-PNET were
      evaluated for tumor location, size, morphology, attenuation/signal intensity,
      (111)In-octreotide uptake, cystic degeneration, and enhancement. Tissue specimens
      were assessed for the extent of stromal fibrosis, vascular density, presence of a
      fibrous pseudocapsule, and tumor grading. Correlation between imaging and
      histopathology was made using the Fisher-Freeman-Halton exact test. RESULTS: NF
      PNET arose from the pancreatic head/neck (n = 10), body (n = 7), and tail (n =
      11). On CT, NF-PNET (mean largest diameter: 4.4 cm) appeared predominantly solid
      (69.6%), well defined (91.3%), and oval (47.8%) in shape. In the late arterial
      phase, NF-PNET appeared mainly hypovascular (55.5%). Septations (30.4%) and
      calcifications (21.7%) were relatively uncommon. On MRI, NF-PNET (mean size: 2.6
      cm) appeared most commonly as solid (57.1%), encapsulated (71.4%), oval (64.2%)
      lesions that were hyperintense on T2-WI (64.3%), and hypo- or isovascular to
      pancreas (66.7%) during the late arterial phase. Cystic NF-PNET (3.8 cm) were not
      significantly larger than solid (3.5 cm) NF-PNET (CT, p = 0.758; MRI, p = 0.451).
      (111)In-octreotide uptake was demonstrated in 5/8 (62.5%) patients. At
      histopathology, NF-PNET were predominantly encapsulated (69.2%); stromal fibrosis
      comprised <33% of the tumor (69.2%), and vascular density was average (46.1%). A
      significant association was demonstrated between the degree of fibrosis and
      hypointensity on T2-WI (p = 0.003). Vascular density, tumor grade, and degree of
      fibrosis did not significantly relate to the pattern of enhancement. CONCLUSIONS:
      NF-PNETs have variable imaging appearances but are most commonly oval shaped,
      solid, and well-defined/encapsulated masses, and hypovascular on late arterial
      and portal venous phase. Cystic degeneration in NF-PNET appears independent of
      tumor size. Low signal intensity on T2-WI correlates with extensive intratumoral
      fibrosis.

PMID- 25989933
TI  - The neural dynamic mechanisms of asymmetric switch costs in a combined Stroop
      task-switching paradigm.
AB  - Switch costs have been constantly found asymmetrical when switching between two
      tasks of unequal dominance. We used a combined Stroop-task-switching paradigm and
      recorded electroencephalographic (EEG) signals to explore the neural mechanism
      underlying the phenomenon of asymmetrical switch costs. The results revealed that
      a fronto-central N2 component demonstrated greater negativity in word switch (cW)
      trials relative to word repeat (wW) trials, and both First P3 and P3b components
      over the parieto-central region exhibited greater positivity in color switch (wC)
      trials relative to color repeat (cC) trials, whereas a contrasting switch-related
      fronto-central SP effect was found to have an opposite pattern for each task.
      Moreover, the time-frequency analysis showed a right-frontal lower alpha band (9
      11 Hz) modulation in the word task, whereas a fronto-central upper alpha band (11
      13 Hz) modulation was exclusively found in the color task. These results provide
      evidence for dissociable neural processes, which are related to inhibitory
      control and endogenous control, contributing to the generation of asymmetrical
      switch costs. 

PMID- 25989934
TI  - Electrokinetic behaviour of porous TiO2-coated implants.
AB  - It is known that the "race for the surface" determining the in vivo response is
      strictly connected to the physico-chemical properties of the material, especially
      at its surface. Accordingly, the study of surface roughness, charge and
      wettability is fundamental to predict the bio-response to the implant. In this
      work, streaming potential was chosen as a reliable method to quantify the solid
      surface charge of hydrothermally treated (HT) TiO2-anatase nano-crystalline
      coatings, grown on titanium substrates. The influence of metal and ionic
      conductance on the zeta potential values was taken into account, allowing for the
      correlation of the surface charge with the coating porosity, the semiconductor
      character of the TiO2 nano-crystals and the metallic nature of the bulk titanium.

PMID- 25989935
TI  - In vitro apatite formation on nano-crystalline titania layer aligned parallel to
      Ti6Al4V alloy substrates with sub-millimeter gap.
AB  - Pure titanium substrates were chemically oxidized with H2O2 and subsequent
      thermally oxidized at 400  degrees C in air to form anatase-type titania layer on
      their surface. The chemically and thermally oxidized titanium substrate (CHT) was
      aligned parallel to the counter specimen such as commercially pure titanium
      (cpTi), titanium alloy (Ti6Al4V) popularly used as implant materials or Al
      substrate with 0.3-mm gap. Then, they were soaked in Kokubo's simulated body
      fluid (SBF, pH 7.4, 36.5  degrees C) for 7 days. XRD and SEM analysis showed that
      the in vitro apatite-forming ability of the contact surface of the CHT specimen
      decreased in the order: cpTi > Ti6Al4V > Al. EDX and XPS surface analysis showed
      that aluminum species were present on the contact surface of the CHT specimen
      aligned parallel to the counter specimen such as Ti6Al4V and Al. This result
      indicated that Ti6Al4V or Al specimens released the aluminum species into the SBF
      under the spatial gap. The released aluminum species might be positively or
      negatively charged in the SBF and thus can interact with calcium or phosphate
      species as well as titania layer, causing the suppression of the primary
      heterogeneous nucleation and growth of apatite on the contact surface of the CHT
      specimen under the spatial gap. The diffusion and adsorption of aluminum species
      derived from the half-sized counter specimen under the spatial gap resulted in
      two dimensionally area-selective deposition of apatite particles on the contact
      surfaces of the CHT specimen. 

PMID- 25989937
TI  - Transoral robotic resection of an adult laryngeal haemangioma and review of the
      literature.
AB  - BACKGROUND: Haemangioma of the adult larynx is an uncommon, benign lesion. The
      optimal surgical method of treating these lesions is controversial because only
      very limited case series are available. This paper reports the results of
      transoral robotic resection of a supraglottic haemangioma in an adult and reviews
      the literature. METHODS AND RESULTS: A 58-year-old woman presented having
      experienced a lump-in-the-throat sensation for 1 year. Investigations on
      laryngoscopy revealed a lobulated, dark red mass in the region of the
      supraglottis. This was successfully excised by transoral robotic excision without
      complications. CONCLUSION: Adult supraglottic haemangiomas can be treated
      successfully with transoral robotic excision; this potentially allows more of the
      surrounding mucosal tissue to be spared and enables easy control of bleeding.

PMID- 25989936
TI  - Development of nanovesicular systems for dermal imiquimod delivery:
      physicochemical characterization and in vitro/in vivo evaluation.
AB  - The aim of the current investigation was to develop and statistically evaluate
      nanovesicular systems for dermal imiquimod delivery. To this purpose,
      transethosomes were prepared with phospholipid, ethanol and different permeation
      enhancers. Conventional ethosomes, with soy phospholipid and ethanol, were used
      as control. The prepared vesicles were characterized for size, zeta potential,
      stability and entrapment efficiency. The optimal transethosomal formulation with
      mean particle size of 82.3 +/- 9.5 nm showed the higher entrapment efficiency
      (68.69 +/- 1.7%). In vitro studies, permeation results of accumulated drug and
      local accumulation efficiency were significantly higher for transethosomes (24.64
      ug/cm(2) and 6.70, respectively) than control (14.45 ug/cm(2) and 3.93,
      respectively). Confocal laser scanning microscopy of rhodamine 6G-loaded
      transethosomes revealed an enhanced retention into the deeper skin layers as
      compared to conventional ethosomes. Besides, Fourier-transform infra-red
      spectroscopy studies were also performed to understand the mechanism of
      interaction between skin and carriers. What's more, results of in vivo studies
      indicated the transethosomes of imiquimod providing the most effectiveness for
      dermal delivery among all of the formulations. These results suggested that
      transethosomes would be a promising dermal carrier for imiquimod in actinic
      keratose treatment.

PMID- 25989938
TI  - Rate Coefficients for the Gas-Phase Reactions of Hydroxyl Radicals with a Series
      of Methoxylated Aromatic Compounds.
AB  - Rate coefficients for the reactions of hydroxyl radicals (OH) with a series of
      oxygenated aromatics (two methoxybenzene and five methoxyphenol isomers) have
      been obtained using the relative kinetic method in 1080 and 480 L photoreactors
      at the University of Wuppertal, Germany. The experiments were realized at 295 +/-
      2 K and 1 bar total pressure of synthetic air using in situ Fourier transform
      infrared spectroscopy for the chemical analysis. The following rate coefficients
      (in units of cm(3) molecule(-1) s(-1)) were determined: methoxybenzene (anisole),
      (2.08 +/- 0.21) * 10(-11); 1-methoxy-2-methylbenzene, (4.56 +/- 0.50) * 10(-11);
      2-methoxyphenol (guaiacol), (5.40 +/- 0.72) * 10(-11); 3-methoxyphenol, (6.93 +/-
      0.67) * 10(-11); 4-methoxyphenol, (5.66 +/- 0.55) * 10(-11); 2-methoxy-4
      methylphenol, (7.51 +/- 0.68) * 10(-11); 2,3-dimethoxyphenol, (7.49 +/- 0.81) *
      10(-11); and 2,6-dimethoxyphenol (syringol), (8.10 +/- 0.98) * 10(-11). The rate
      coefficients for the reactions of OH with 2,3-dimethoxyphenol and 1-methoxy-2
      methylbenzene are first time measurements. The rate coefficients determined in
      this work are compared with previous determinations reported in the literature
      and also with the values estimated using a structure-activity relationship
      method. A comparison is performed between the OH rate coefficients obtained for
      methoxylated aromatics with those of other substituted aromatics in order to
      understand the influence of the type, number, and position of the different
      substituents on the reactivity of aromatics toward OH. In addition, a comparison
      is made between the OH and Cl rate coefficients for the compounds. The principal
      atmospheric sink of these methoxylated aromatic compounds during daytime is their
      reaction with OH radicals. The corresponding lifetimes for reaction with OH
      radicals and Cl atoms are 2-8 and 11-50 h, respectively. 

PMID- 25989940
TI  - The association between socio-economic position and diet quality in Australian
      adults.
AB  - OBJECTIVE: We aimed to investigate the association between multiple measures of
      socio-economic position (SEP) and diet quality, using a diet quality index
      representing current national dietary guidelines, in the Australian adult
      population. DESIGN: Cross-sectional study. Linear regression analyses were used
      to estimate the association between indicators of SEP (educational attainment,
      level of income and area-level disadvantage) and diet quality (measured using the
      Dietary Guideline Index (DGI)) in the total sample and stratified by sex and age
      (<=55 years and >55 years). SETTING: A large randomly selected sample of the
      Australian adult population. SUBJECTS: Australian adults (n 9296; aged >=25
      years) from the Australian Diabetes, Obesity and Lifestyle Study. RESULTS: A
      higher level of educational attainment and income and a lower level of area-level
      disadvantage were significantly associated with a higher DGI score, across the
      gradient of SEP. The association between indicators of SEP and DGI score was
      consistently stronger among those aged <=55 years compared with their older
      counterparts. The most disadvantaged group had a DGI score between 2 and 5 units
      lower (depending on the marker of SEP) compared with the group with the least
      disadvantage. CONCLUSIONS: A higher level of SEP was consistently associated with
      a higher level of diet quality for all indicators of SEP examined. In order to
      reduce socio-economic inequalities in diet quality, healthy eating initiatives
      need to act across the gradient of socio-economic disadvantage with a
      proportionate focus on those with greater socio-economic disadvantage.

PMID- 25989939
TI  - Biomaterial based cardiac tissue engineering and its applications.
AB  - Cardiovascular disease is a leading cause of death worldwide, necessitating the
      development of effective treatment strategies. A myocardial infarction involves
      the blockage of a coronary artery leading to depletion of nutrient and oxygen
      supply to cardiomyocytes and massive cell death in a region of the myocardium.
      Cardiac tissue engineering is the growth of functional cardiac tissue in vitro on
      biomaterial scaffolds for regenerative medicine application. This strategy relies
      on the optimization of the complex relationship between cell networks and
      biomaterial properties. In this review, we discuss important biomaterial
      properties for cardiac tissue engineering applications, such as elasticity,
      degradation, and induced host response, and their relationship to engineered
      cardiac cell environments. With these properties in mind, we also emphasize in
      vitro use of cardiac tissues for high-throughput drug screening and disease
      modelling. 

PMID- 25989941
TI  - Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine
      carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous
      cell carcinoma.
AB  - BACKGROUND: As the comprehensive genomic analysis of small cell lung cancer
      (SCLC) progresses, novel treatments for this disease need to be explored. With
      attention to the direct connection between the receptor tyrosine kinases (RTKs)
      of tumor cells and the pharmacological effects of specific inhibitors, we
      systematically assessed the RTK expressions of high-grade neuroendocrine
      carcinomas of the lung [HGNECs, including SCLC and large cell neuroendocrine
      carcinoma (LCNEC)]. PATIENTS AND METHODS: Fifty-one LCNEC and 61 SCLC patients
      who underwent surgical resection were enrolled in this research. As a control
      group, 202 patients with adenocarcinomas (ADCs) and 122 patients with squamous
      cell carcinomas (SQCCs) were also analyzed. All the tumors were stained with
      antibodies for 10 RTKs: c-Kit, EGFR, IGF1R, KDR, ERBB2, FGFR1, c-Met, ALK, RET,
      and ROS1. RESULTS: The LCNEC and SCLC patients exhibited similar
      clinicopathological characteristics. The IHC scores for each RTK were almost
      equivalent between the LCNEC and SCLC groups, but they were significantly
      different from those of the ADC or SQCC groups. In particular, c-Kit was the only
      RTK that was remarkably expressed in both LCNECs and SCLCs. On the other hand,
      about 20 % of the HGNEC tumors exhibited strongly positive RTK expression, and
      this rate was similar to those for the ADC and SQCC tumors. Intriguingly,
      strongly positive RTKs were almost mutually exclusive in individual tumors.
      CONCLUSIONS: Compared with ADC or SQCC, LCNEC and SCLC had similar expression
      profiles for the major RTKs. The exclusive c-Kit positivity observed among HGNECs
      suggests that c-Kit might be a distinctive RTK in HGNEC.

PMID- 25989943
TI  - The Epidemiology of Prehospital Emergency Responses for Older Adults in a
      Provincial EMS System.
AB  - OBJECTIVES: Societal aging is expected to impact the use of emergency medical
      services (EMS). Older adults are known as high users of EMS. Our primary
      objective was to quantify the rate of EMS use by older adults in a Canadian
      provincial EMS system. Our secondary objective was to compare those transported
      to those not transported. METHODS: We analysed data from a provincial EMS
      database for emergency responses between January 1, 2010 and December 31, 2010
      and included all older adults (>=65 years) requesting EMS for an emergency call.
      We described EMS use in relation to age, sex, and resources. RESULTS: There were
      30,653 emergency responses for older adults in 2010, representing close to 50% of
      the emergency call volume and an overall response rate of 202.8 responses per
      1,000 population 65 years and older. The mean age was 79.9+/-8.5 years for those
      57.3% who were female. The median paramedic-determined Canadian Triage and Acuity
      Scale (CTAS) score was 3 and the mean on-scene time was 24.2 minutes. Non
      transported calls (12.3%) for the elderly involved predominantly (54.9%) female
      patients of similar mean age (78.3 years) but lower acuity (CTAS 5) and longer
      average on-scene times (32.6 minutes). CONCLUSIONS: We confirmed the increasingly
      high rate of EMS use with age to be consistent with other industrialized
      populations. The low-priority and non-transport calls by older adults consumed
      considerable resources in this provincial system and might be the areas most
      malleable to meet the challenges facing EMS systems.

PMID- 25989942
TI  - Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo
      hepatocellular carcinoma model.
AB  - PURPOSE: A previous study showed that flavopiridol increased doxorubicin
      sensitivity in hypoxic hepatocellular carcinoma (HCC) cells by increasing
      apoptosis through suppressing hypoxia-inducible N-myc downstream-regulated gene-1
      (NDRG1) expression. However, this has not been investigated in an in vivo HCC
      model. Therefore, we aimed to elucidate whether the combination of doxorubicin
      and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model.
      METHODS: An HCC mouse model was established by implanting C3H/He mouse with MH134
      cells. Then, doxorubicin with or without flavopiridol was injected. The anti
      tumor efficacy was assessed by evaluating tumor volumes, and the underlying
      mechanism was investigated by quantifying apoptotic cells, the Ki-67
      proliferation index, and microvessel densities (MVDs). Immunohistochemistry of
      NDRG1 was performed to determine the underlying mechanism. RESULTS: Tumor growth
      was significantly suppressed in the doxorubicin + flavopiridol combination group
      compared to the other three groups. The percentage of apoptotic cells was
      significantly higher, and Ki-67-positive proliferating cells were significantly
      lower in the combination group compared to the other groups; however, MVDs were
      not significantly different across the groups. Increased apoptosis by
      flavopiridol occurred by suppressing hypoxia-inducible NDRG1 expression.
      CONCLUSIONS: These results show that a combination of doxorubicin and
      flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model. This
      synergistic effect of combination therapy was attributed to increased apoptosis
      and decreased proliferation of tumor cells rather than decreased angiogenesis.
      These findings suggest that flavopiridol might be an effective adjuvant therapy
      to doxorubicin-resistant HCC cells by inducing apoptosis through suppression of
      NDRG1 expression.

PMID- 25989944
TI  - PCSK9 inhibitors and neurocognitive adverse events: exploring the FDA directive
      and a proposal for N-of-1 trials.
AB  - Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel
      class of medications that greatly lower low-density lipoprotein cholesterol (LDL
      C) by upregulating LDL receptor availability. In early 2014, the US Food and Drug
      Administration (FDA) directed developers of PCSK9 inhibitors to monitor
      neurocognitive adverse effects and consider neurocognitive testing in at least a
      subset of participants in ongoing late-stage trials. Available trial evidence
      indicates that neurocognitive adverse events may occur more commonly in
      individuals receiving an antibody to PCSK9, but these events are uncommon and
      have not been associated with on-treatment LDL-C levels. Moreover, it is unclear
      to what extent closer monitoring of trial participants allocated to PCSK9
      inhibitors has led to an ascertainment bias. Regardless, further trial data are
      needed, and long-term outcomes trials are ongoing, with at least one including a
      neurocognitive substudy. Considering lessons learned from the statin experience,
      high-quality prospective cohort studies and randomized trials may not be enough
      to allay concerns or settle debate since the focus of effect in these studies is
      the group average. Therefore, we suggest that n-of-1 trials could be considered
      to bring the focus to the individual while retaining the benefits of blinding and
      randomization in evidence generation. Ultimately, any neurocognitive adverse
      effects that might exist with PCSK9 inhibition and lipid lowering must be weighed
      against potential benefits of therapy, including avoidance of myocardial
      infarction and stroke, and a reduced risk of dementia due to neurovascular
      benefits from long-term lipid lowering. 

PMID- 25989945
TI  - Effect of multiple repeat cesarean sections on maternal morbidity: data from
      southeast Turkey.
AB  - BACKGROUND: Cesarean section (CS) is one of the most common obstetric procedures
      worldwide and an increased rate of cesarean section has been observed in recent
      studies. Maternal and fetal mortality and morbidity associated with cesarean
      section is an important health problem worldwide. This requires the evaluation of
      the effect of repeated cesarean delivery on maternal morbidity. MATERIAL/METHODS:
      A total of 2460 patients who underwent delivery by CS at a center in southeast
      Turkey between January 2012 and January 2014 (24 months) were included in the
      study. The patients were divided into 5 groups according to the number of CSs,
      and the maternal and neonatal outcomes of the groups were retrospectively
      evaluated. RESULTS: A statistically significant difference was found between the
      groups in terms of maternal age, education level, time of hospitalization,
      operating time, the presence of dense adhesions, bowel and bladder injury, the
      presence of placenta previa, hysterectomy, blood transfusion requirements, and
      need for intensive care (p<0.05). Placenta previa (OR, 11.7; 95% CI, 2.6-53.2)
      and placenta accreta (OR, 12.2; 95% CI, 3.9-37.8) were found to be important risk
      factors in terms of the need for hysterectomy. No statistically significant
      difference was found between the groups for gestational age at birth, birth
      weight, fifth-minute APGAR score, preoperative and postoperative hemoglobin
      levels, uterine rupture, wound infection, wound dehiscence, placenta accreta,
      maternal death, and endometritis (p>0.05). A total of 4 or more CSs was
      identified as the critical level for most of the major complications.
      CONCLUSIONS: An increasing number of CSs is accompanied by serious maternal
      complications. Four or more CSs are of especially critical importance. Decreasing
      the number of cesarean sections is required to decrease relevant complications.
      Vaginal birth after CS is an option that should be recommended to the patient.

PMID- 25989947
TI  - Healthcare-associated outbreaks due to Mucorales and other uncommon fungi.
AB  - BACKGROUND: Healthcare-associated outbreaks of fungal infections, especially with
      uncommon and emerging fungi, have become more frequent in the past decade.
      MATERIALS AND METHOD: Here, we reviewed the history and definition of healthcare
      associated outbreaks of uncommon fungal infections and discussed the principles
      of investigating, containing and treatment of these outbreaks. RESULTS: In case
      of these uncommon diseases, occurrence of two or more cases in a short period is
      considered as an outbreak. Contaminated medical devices and hospital environment
      are the major sources of these outbreaks. Care must be taken to differentiate a
      real infection from colonization or contamination. Defining and identifying
      cases, describing epidemiologic feature of cases, finding and controlling the
      source of the outbreak, treating patients, and managing asymptomatic exposed
      patients are main steps for outbreak elimination. These fungal outbreaks are not
      only difficult to detect but also hard to treat. Early initiation of appropriate
      antifungal therapy is strongly associated with improved outcomes in infected
      patients. Choice of antifungal drugs should be made based on spectrum,
      pharmacodynamic and pharmacokinetic characteristics and adverse effects of
      available drugs. Combination antifungal therapy and surgical intervention may be
      also helpful in selected cases. CONCLUSIONS: A multidisciplinary approach and
      close collaboration between all key partners are necessary for successful control
      of fungal outbreaks.

PMID- 25989949
TI  - Cross-talk between systemic and cerebral inflammation in depressive disorders:
      Relevance to pathogenesis and treatment.

PMID- 25989950
TI  - The association of crown-rump length discrepancy with birthweight discordance in
      spontaneous versus IVF monochorionic twins: a multicenter study.
AB  - OBJECTIVE: The objective of this study was to compare the associations of crown
      rump length (CRL) discrepancy with birthweight discordance in spontaneous versus
      in vitro fertilization (IVF) monochorionic (MC) twin pregnancies. METHOD: This is
      a multicenter retrospective study on women with twin pregnancies assessed for
      nuchal translucency between January 1997 and July 2013. The study group was
      subdivided into MC twins conceived spontaneously and after IVF. Pregnancies with
      later fetal death or twin transfusion syndrome were excluded. A large-weight
      discordance was defined as a difference of birthweights of >15%. RESULTS: The
      study group included 171 pregnancies; of them, 142 (83%) were spontaneous and 29
      (17%) were IVF conceived. In the entire cohort, we found a significant
      correlation between birthweight discordance and CRL discrepancy (r = 0.173, P <
      0.05). While a significant correlation was found between CRL discrepancy and
      birthweight discordance in spontaneous-conceived pregnancies (n = 142, r = 0.24,
      P = 0.005), such correlation was not present in IVF pregnancies (n = 29, r = 
      0.7, P = 0.724). A logistic regression analysis found significant odds of larger
      weight discordance for each increase of 1% in CRL discrepancy among spontaneously
      conceived pregnancies (odds ratio = 1.1, confidence interval = 1.03-1.2, P =
      0.005). A receiver operating characteristic (ROC) for large-weight discordance in
      the spontaneously conceived pregnancies demonstrated an area under the ROC curve
      of 0.613 (P = 0.039). CONCLUSION: The significant correlation between CRL
      discrepancy and birthweight discordance in spontaneous versus IVF MC twin
      pregnancies might suggest differential monozygotic twinning process.

PMID- 25989951
TI  - Applicability of the ICD-11 proposal for PTSD: a comparison of prevalence and
      comorbidity rates with the DSM-IV PTSD classification in two post-conflict
      samples.
AB  - BACKGROUND: The World Health Organization recently proposed significant changes
      to the posttraumatic stress disorder (PTSD) diagnostic criteria in the 11th
      edition of the International Classification of Diseases (ICD-11). OBJECTIVE: The
      present study investigated the impact of these changes in two different post
      conflict samples. METHOD: Prevalence and rates of concurrent depression and
      anxiety, socio-demographic characteristics, and indicators of clinical severity
      according to ICD-11 in 1,075 Cambodian and 453 Colombian civilians exposed to
      civil war and genocide were compared to those according to the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). RESULTS: Results
      indicated significantly lower prevalence rates under the ICD-11 proposal (8.1%
      Cambodian sample and 44.4% Colombian sample) compared to the DSM-IV (11.2%
      Cambodian sample and 55.0% Colombian sample). Participants meeting a PTSD
      diagnosis only under the ICD-11 proposal had significantly lower rates of
      concurrent depression and a lower concurrent total score (depression and anxiety)
      compared to participants meeting only DSM-IV diagnostic criteria. There were no
      significant differences in socio-demographic characteristics and indicators of
      clinical severity between these two groups. CONCLUSIONS: The lower prevalence of
      PTSD according to the ICD-11 proposal in our samples of persons exposed to a high
      number of traumatic events may counter criticism of previous PTSD classifications
      to overuse the PTSD diagnosis in populations exposed to extreme stressors. Also
      another goal, to better distinguish PTSD from comorbid disorders could be
      supported with our data.

PMID- 25989952
TI  - EMDR for Syrian refugees with posttraumatic stress disorder symptoms: results of
      a pilot randomized controlled trial.
AB  - BACKGROUND: The most common mental health problems among refugees are depression
      and posttraumatic stress disorder (PTSD). Eye movement desensitization and
      reprocessing (EMDR) is an effective treatment for PTSD. However, no previous
      randomized controlled trial (RCT) has been published on treating PTSD symptoms in
      a refugee camp population. OBJECTIVE: Examining the effect of EMDR to reduce the
      PTSD and depression symptoms compared to a wait-list condition among Syrian
      refugees. METHOD: Twenty-nine adult participants with PTSD symptoms were randomly
      allocated to either EMDR sessions (n=15) or wait-list control (n=14). The main
      outcome measures were Impact of Event Scale-Revised (IES-R) and Beck Depression
      Inventory (BDI-II) at posttreatment and 4-week follow-up. RESULTS: Analysis of
      covariance showed that the EMDR group had significantly lower trauma scores at
      posttreatment as compared with the wait-list group (d=1.78, 95% CI: 0.92-2.64).
      The EMDR group also had a lower depression score after treatment as compared with
      the wait-list group (d=1.14, 95% CI: 0.35-1.92). CONCLUSION: The pilot RCT
      indicated that EMDR may be effective in reducing PTSD and depression symptoms
      among Syrian refugees located in a camp. Larger RCTs to verify the (cost-)
      effectiveness of EMDR in similar populations are needed.

PMID- 25989953
TI  - Treatment of Unfit Patients With Advanced Non-Small-Cell Lung Cancer: Definition
      Criteria According an Expert Panel.
AB  - The assessment of special categories of non-small-cell lung cancer (NSCLC)
      patients requires a comprehensive analysis of all factors potentially influencing
      the daily quality of life and the relative contribution of tumor-related symptoms
      on the overall patient health status. While for elderly patients prospective
      evidence and recommendations allow clinicians to better address their patients to
      a shared treatment, a paucity of reliable data refers to treatment opportunities
      for these patients, termed frail or unfit, who are not considered eligible for
      chemotherapy usually administered to adult patients. This consensus was inspired
      by the absence of clear criteria to define the category of unfit patients in the
      context of advanced NSCLC in order to share all the available tools for their
      classification and evaluation and to support decisions for clinical practice on a
      daily basis. After review of the literature and panelist consensus, a series of
      items was identified as relevant: age, performance status, renal function, heart
      failure, previous cerebrovascular events, uncontrolled hypertension, neuropathy,
      hearing loss, symptomatic brain metastases, severe psychiatric disorders, and
      absence of caregiver support. On the basis of these factors, a treatment
      algorithm for clinical practice to categorize unfit NSCLC patient into 3 major
      clinical scenarios was defined: (1) unfit for cisplatin-based chemotherapy, (2)
      unfit for carboplatin-based chemotherapy, and (3) unfit for single-agent
      chemotherapy. 

PMID- 25989954
TI  - Gaps in knowledge about personality disorders in homeless populations (commentary
      for article by Whitbeck, Armenta, and Welch-Lazoritz, "Borderline personality
      disorder and Axis I psychiatric and substance use disorders among women
      experiencing homelessness in three US cities").

PMID- 25989948
TI  - Aptamer-Functionalized Nanoparticles as "Smart Bombs": The Unrealized Potential
      for Personalized Medicine and Targeted Cancer Treatment.
AB  - Conventional delivery of chemotherapeutic agents leads to multiple systemic side
      effects and toxicity, limiting the doses that can be used. The development of
      targeted therapies to selectively deliver anti-cancer agents to tumor cells
      without damaging neighboring unaffected cells would lead to higher effective
      local doses and improved response rates. Aptamers are single-stranded
      oligonucleotides that bind to target molecules with both high affinity and high
      specificity. The high specificity exhibited by aptamers promotes localization and
      uptake by specific cell populations, such as tumor cells, and their conjugation
      to anti-cancer drugs has been explored for targeted therapy. Advancements in the
      development of polymeric nanoparticles allow anti-cancer drugs to be encapsulated
      in protective nonreactive shells for controlled drug delivery with reduced
      toxicity. The conjugation of aptamers to nanoparticle-based therapeutics may
      further enhance direct targeting and personalized medicine. Here we present how
      the combinatorial use of aptamer and nanoparticle technologies has the potential
      to develop "smart bombs" for targeted cancer treatment, highlighting recent pre
      clinical studies demonstrating efficacy for the direct targeting to particular
      tumor cell populations. However, despite these pre-clinical promising results,
      there has been little progress in moving this technology to the bedside. 

PMID- 25989957
TI  - Successful treatment with canakinumab of a paediatric patient with resistant
      Behcet's disease.

PMID- 25989955
TI  - Elevated ratio of acylated to unacylated ghrelin in children and young adults
      with Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive
      to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may
      be involved in the underlying mechanisms of the switch. The purpose of this study
      is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS
      and investigate their associations with hyperphagia. This is a cross-sectional
      clinical study conducted in three PWS expert centers in the Netherlands and
      France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients
      with PWS (0.2-29.4 years) and compared with 50 age-matched obese subjects (4.3
      16.9 years) and 39 healthy controls (0.8-28.6 years). AEBSF was used to inhibit
      deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels
      as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml,
      resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p =
      0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS
      and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16).
      The reason for the higher AG/UAG ratio in PWS and obese was, however, completely
      different, as PWS had a high AG and obese a very low UAG. PWS patients without
      weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in
      contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG
      ratio. The switch to excessive weight gain in PWS seems to coincide with an
      increase in the AG/UAG ratio, even prior to the start of hyperphagia.

PMID- 25989956
TI  - Societal preferences for rheumatoid arthritis treatments: evidence from a
      discrete choice experiment.
AB  - OBJECTIVE: There is a concern that cost-effectiveness analysis using quality
      adjusted life years does not capture all valuable benefits of treatments. The
      objective of this study was to determine the value society places on aspects of
      RA treatment to inform policymaking. METHODS: A discrete choice experiment was
      administered to a representative sample of the Canadian general population. The
      discrete choice experiment, developed using focus groups, had seven attributes
      (route and frequency of administration, chance of benefit, chance of serious and
      minor side effects, confidence in evidence and life expectancy). A conditional
      logit regression model was used to estimate the significance and relative
      importance of attributes in influencing preferences on the quality-adjusted life
      years scale. RESULTS: Responses from 733 respondents who provided rational
      responses were analysed. Six attribute levels within four attributes
      significantly influenced preferences for treatments: a willingness to trade a
      year of life expectancy over a 10-year period to increase the probability of
      benefiting from treatment, or two-thirds of a year to reduce minor or serious
      side effects to the lowest level or improve the confidence in benefit/side-effect
      estimates. There was also some evidence of a preference for oral drug delivery,
      though a subgroup analysis suggested this preference was restricted to injection
      naive respondents. CONCLUSION: Our results suggest society values the degree of
      confidence in the estimates of risks and benefits of RA treatments and the route
      of administration, as well as benefits and side effects. This study provides
      important evidence to policymakers determining the cost-effectiveness of
      treatments in arthritis.

PMID- 25989958
TI  - Multiple arterial injuries and prolonged cholesterol feeding do not increase
      percent lumen stenosis: impact of compensatory enlargement in the microswine
      model.
AB  - While the swine model is frequently utilized in the study of arterial
      intervention, it has been difficult to create severe peripheral arterial stenosis
      without total thrombotic occlusion with a single arterial injury and short-term
      cholesterol feeding. The combination of multiple arterial injuries and prolonged
      cholesterol feeding was explored in an effort to create lesions with significant
      luminal compromise. Nineteen microswine were divided into two groups and fed a
      high cholesterol diet followed by multiple balloon injuries of the iliac
      arteries. We conclude that repeated balloon injuries and longer cholesterol
      feeding significantly increase areas of plaque and necrotic core but do not
      increase percent stenosis because of arterial compensatory enlargement. The
      microswine iliac arteries enlarge in relation to plaque area and repeated balloon
      injuries. The compensatory lumen enlargement may be one of the factors resulting
      in significant angiographic underestimation of plaque area during the early stage
      of the atherosclerotic disease, but it may functionally delay important lumen
      stenosis until the lesion occupies 40% of the internal elastic lamina area. This
      study suggests that repeated injury and longer cholesterol feeding to increase
      percent stenosis may not be cost effective in this model. However, this model is
      good for studying an increase in plaque accumulation. 

PMID- 25989959
TI  - Temporal changes in the surgical pathology of prosthetic aortic valves: a study
      of 157 cases spanning 26 years (1970-1995).
AB  - The objective of this study was to identify time-related changes in the types,
      functional states, and complications of explanted prosthetic aortic valves. All
      patients having a prosthetic aortic valve replacement at Mayo Clinic Rochester
      during the years 1970, 1975, 1980, 1985, 1990, and 1995 were identified. By
      reviewing the medical records and pathologic specimens, 157 valves were
      classified by type, functional state, complications, and duration of
      implantation. Among the 157 patients (118 men and 39 women), 48% had mechanical
      valves, 37% bioprostheses, 14% homografts, and 1% teflon trileaflet.
      Regurgitation was the most common functional state both overall (69%) and in each
      year. The mean age of patients at reoperation increased from 53 years in 1970 to
      60 years in 1995, during which time the mean duration of implantation increased
      from 2.7 to 9.2 years. Although mechanical valves represented 70% of explanted
      aortic prostheses in 1970, they accounted for only 37% in 1995. The percentage of
      valves failing from structural degeneration decreased, from 58% in 1980 to an
      average of 36% thereafter, while the percentage for prosthetic aortic
      endocarditis increased from 0% in 1980 to an average of 19% during 1985, 1990,
      and 1995. Endocarditis affected men in 19 (83%) of the 23 cases and was caused by
      staphylococci or streptococci in 18 (78%). The development of newer prosthetic
      valves, changes in surgeons' preferences for them, and improvements in diagnosis,
      treatment, and prevention have contributed to temporal fluctuations in the
      relative frequencies of complications and associated functional states. 

PMID- 25989960
TI  - Participation of nitric oxide and peroxynitrite in the development of myocardial
      tissue damage in acute myocardial infarction.
AB  - Many factors, including superoxides, contribute to tissue damage in acute
      myocardial infarction (AMI). Excess nitric oxide (NO) produced by inducible NO
      synthase (iNOS) has also been reported to participate in myocardial injury
      associated with AMI, but its exact role remains unclear. To elucidate the role of
      NO and peroxynitrite in the pathogenesis of myocardial injury associated with
      AMI, we examined the expression of iNOS in the autopsied specimens of the left
      ventricle obtained from 15 patients with AMI and five with old MI by
      immunohistochemistry using an anti-iNOS polyclonal antibody. The distribution of
      nitrotyrosine was also examined immunohistochemically. In patients who died from
      12 hours to 3 weeks after the infarction, positive immunoreactivity for iNOS was
      observed in residual myocytes, macrophages, and vascular endothelial cells in the
      peri-infarcted area. Degenerating myocytes in that area in all of that group
      showing positive staining for iNOS were also stained positive for anti
      nitrotyrosine antibody selfsame. These findings were not observed in the
      myocardial specimens obtained from patients who died within 12 hours after the
      onset of AMI, showing a minimal number of inflammatory cells, or in the specimens
      from patients with an old myocardial infarction, which showed scar tissue and no
      cellular infiltration. Inducible NOS and nitrotyrosine were expressed in damaged
      myocardium from patients with AMI, suggesting that the NO radical and
      peroxynitrite are involved in the pathogenesis of myocardial damage. 

PMID- 25989961
TI  - Versican, biglycan, and decorin protein expression patterns in coronary arteries:
      analysis of primary and restenotic lesions.
AB  - The pathobiology of rapid intimal thickening following balloon angioplasty
      remains unsettled. Proteoglycans (PGs) expressed by smooth-muscle cells (SMCs)
      are known to participate in vascular responses to injury. In this analysis,
      patients ranging from age 48 to 79 years (mean = 58), underwent atherectomy for
      36 restenotic tissues (taken 64 to 345 days postangioplasty; mean = 108) and for
      10 primary atherosclerotic plaques. Tissues were formaldehyde-fixed, paraffin
      embedded, and histochemically and immunohistochemically stained to determine the
      temporal and semi-quantitative contribution of major vessel wall PGs, versican,
      biglycan, and decorin. Versican was the most striking PG in the neointima of
      restenotic vessels, including a prominent pericellular pattern corresponding to
      proliferative SMCs, as well as a large extracellular accumulation. Biglycan was
      limited to the most loose and proliferative neointima and stained less than in
      primary plaques. Decorin staining was virtually absent in the most proliferative
      neointimal tissue, whereas it was quite striking in established primary lesions.
      Thus the earliest response to balloon injury of a coronary artery includes
      striking expression of versican protein, but the limited expression of biglycan
      differs from the prominence of the PG in primary atherosclerosis. Versican
      expression in restenotic lesions is similar to that seen previously in transplant
      arteriopathy, but the lack of biglycan in atherectomy specimens from restenosis
      sites is distinctively different from that seen in rapidly progressive transplant
      vascular disease. 

PMID- 25989962
TI  - Pathologic evidence of arrhythmogenic cardiomyopathy and myocarditis in two
      siblings.
AB  - This report describes the case of two siblings who underwent heart
      transplantation with a clinical diagnosis of mildly dilated cardiomyopathy.
      Pathological examination of the hearts revealed arrhythmogenic (right
      ventricular) cardiomyopathy, adipose type, associated with biventricular
      myocarditis in both the recipients' hearts. Family history revealed the
      occurrence of dilated cardiomyopathy and myocarditis in their father and his
      sister. To our knowledge, this is the first pathological demonstration of
      arrhythmogenic cardiomyopathy and myocarditis in siblings. We think this report
      substantiates a genetic ground for the relationship between these two heart
      conditions. 

PMID- 25989963
TI  - Hemophagocytic syndrome complicating cardiac transplantation.
AB  - Infection-associated hemophagocytic syndrome is one of the hemophagocytic
      disorders, and is most often seen in the pediatric population, typically in the
      setting of immunosuppression. We present the case of a 33-year-old man who had
      been well for more than 3 years following cardiac transplantation until he
      developed the infection-associated hemophagocytic syndrome. The patient had a
      fulminant downhill course, dying in shock 10 weeks after his first presentation.
      Serologic studies for Epstein-Barr virus suggested a remote infection; other
      viral and microbiologic studies were negative. The only previous report of
      infection-associated hemophagocytic syndrome complicating cardiac transplant
      appears to be that of a pediatric patient. The case presented illustrates the
      difficulties in antemortem diagnosis of this disorder, and in its treatment. 

PMID- 25989964
TI  - Multiple cardiac lipomas and sudden death: a case report and literature review.
AB  - We report a unique case of multiple subepicardial lipomas found in a 15-year-old
      girl who died suddenly. This case is, to the best of our knowledge, unique in
      several aspects. First, the large lipomas arose extensively from the surface of
      the heart, infiltrating the walls of all four chambers, and the left ventricle
      was most severely involved. Second, the lipomas were associated with lipomatous
      hypertrophy of the interatrial groove. Third, multiple lipomas involved the
      organs of two systems, namely, the heart and the stomach. We speculate that it
      was fatty infiltration of the left ventricle that led to ventricular fibrillation
      and sudden death. 

PMID- 25989965
TI  - Long-Term Effects of Novel Combination Coating Anti-CD34 Antibody Applied on
      Sirolimus-Eluting Stents.
AB  - OBJECTIVES: We investigated whether the combination coating of a novel
      "prohealing coating" hyaluronan-chitosan (HC) and anti-CD34 antibody applied on
      an SES (HCASES) can reduce neointimal formation while promoting
      endothelialization compared to either agent alone. BACKGROUND: Drug-eluting
      stents have considerably reduced the incidence of in-stent restenosis compared
      with bare metal stents. However, the beneficial effect of drug elution is
      overshadowed by delayed re-endothelialization as well as later "catch-up"
      proliferation related to the drug. METHODS: Three different stents: Sirolimus
      eluting stents (SES), Genous anti-CD34 antibody stents (GS), and the combination
      of HC-anti-CD34 antibody with sirolimus-eluting stents (HCASES) were deployed in
      54 normal porcine coronary arteries and harvested for scanning electron
      microscopy (SEM) and histological analysis at 60, 90, and 120 days. RESULTS: At
      60 and 90 days, SEM analysis showed stent surface endothelial coverage was nearly
      completed in the HCASES (87 +/- 3%, 95 +/- 3%) compared with that in the SES (68
      +/- 6%, 77 +/- 8%, P = 0.03). Histological examination at 90 days showed that the
      HCASES group had less percentage of stenosis than the GS group (P < 0.05). At 120
      days, SEM showed a significantly higher extent of endothelial coverage above
      struts in the HCASES (96 +/- 2%) and the GS (95 +/- 3%) as compared with the SES
      group (66 +/- 3%; P = 0.02). The HCASES group showed less stenosis than that in
      the GS group (P < 0.05), but it was not significantly different from the SES
      group (P = 0.063). CONCLUSIONS: Histological and SEM analyses demonstrate that
      the HCASES can reduce neointimal formation and inflammation while promoting
      endothelialization in the long term.

PMID- 25989966
TI  - S-doped Na2Ti6O13@TiO2 core-shell nanorods with enhanced visible light
      photocatalytic performance.
AB  - S-doped Na2Ti6O13@TiO2 (S-TTO) core-shell nanorods, with exposed anatase TiO2
      {101} facets, were synthesized by a facile calcination method. It was found that
      the addition of thiourea as the sulfur precursor was beneficial for the formation
      of anatase TiO2 with a better crystallinity and the doped sulfur atoms favorably
      stabilized the anatase structure. The substitution of Ti(4+) by S(6+) in the
      lattice of S-TTO gave rise to the visible light response and increased the amount
      of active groups typically as a hydroxyl radical adsorbed onto the catalyst
      surface. With the formation of the Ti-O-S bond, partial electrons could be
      transferred from S to O atoms. The electron-deficient S atoms might capture e(-)
      and thus inhibit the recombination of photogenerated electron-hole pairs.
      Meanwhile, a closely contacted interface was formed between Na2Ti6O13 and anatase
      TiO2, resulting in a nanoscale heterojunction structure to speed up the
      separation rate of photogenerated charge carriers. The exposed anatase {101}
      facets could act as possible reservoirs of the photogenerated electrons, yielding
      a highly reactive surface for the reduction of O2 to O2(-) and thus the decrease
      of recombination probability of electron-hole pairs. In addition, the
      anisotropically shaped titanate nanorods provided a pathway for the quick
      transport of charge carriers throughout the longitudinal direction. The combined
      effects of S doping, nano-heterojunction formation and morphology engineering led
      to an obviously enhanced photocatalytic performance for the degradation of
      methylene blue (MB) solution under visible light irradiation. The corresponding
      photocatalytic mechanism was investigated and discussed in detail. The present
      work may provide an insight into the fabrication of delicate composite
      photocatalysts with excellent performance. 

PMID- 25989967
TI  - Platinum decorated functionalized defective acetylene black; a promising cathode
      material for the oxygen reduction reaction.
AB  - A novel single-pot method to exfoliate and functionalize acetylene black is
      proposed. The deliberate functionalization was found to enhance the intrinsic
      oxygen reduction efficiency along with the nucleation and growth of platinum nano
      particles on the surface. The resulting material showed enormously high oxygen
      reduction reactivity compared to its commercial counterparts. 

PMID- 25989968
TI  - GlideScope vs. C-MAC for Awake Upright Laryngoscopy.
AB  - BACKGROUND: Combining video laryngoscopy with awake upright intubation may
      provide an alternative modality of endotracheal intubation (ETI) that avoids
      pitfalls associated with traditional ETI. OBJECTIVE: We compared laryngoscopic
      views and time intervals between the GlideScope (GVL) and C-MAC video
      laryngoscopes using a face-to-face technique in awake, upright volunteers.
      METHODS: We performed a prospective, randomized, crossover study performing awake
      upright laryngoscopy on healthy volunteers. Under local anesthesia, participants
      had awake upright laryngoscopy performed by a resident and attending physician,
      both operating GVL and C-MAC in random order. We recorded times to first view of
      the glottis and best view of the glottis, percentage of glottic opening (POGO)
      score, Cormack-Lehane grade, and number of attempts needed to visualize the
      glottis. RESULTS: We enrolled 26 subjects, 10 male and 16 female (mean age of
      31.9 years). GVL had shorter time to first view of the glottis than the CMAC
      (median 7 s; interquartile range [IQR]: 6.5-18 s vs. 9 s; IQR: 8-13; p = 0.005).
      However, time to best view of the glottis was similar between devices (GVL 10.25
      s; IQR: 8.5-15 s; CMAC 13 s; IQR: 10-16 s; p = 0.238). GVL had higher POGO median
      scores (61.25; IQR: 45.5-87.5) compared to C-MAC (5; IQR: 2.5-20.5) (p < 0.001)
      and improved Cormack-Lehane views (median 1.5 views; IQR: 1-2 views) compared to
      C-MAC (median 2 views; IQR: 2-3 views; p = 0.001). Number of attempts were
      similar across devices (median 1; IQR, 1-1.5) for both GVL and C-MAC (p = 0.764).
      CONCLUSIONS: GlideScope provides superior views to C-MAC in awake upright
      laryngoscopy in healthy volunteers.

PMID- 25989969
TI  - Myocardial Infarction in the Setting of Anaphylaxis to Celecoxib: A Case of
      Kounis Syndrome.
AB  - BACKGROUND: Acute coronary syndromes in the setting of an allergic or
      hypersensitivity reaction are known as Kounis syndrome. The syndrome involves
      release of inflammatory mediators after an allergen exposure that leads to
      coronary artery vasospasm or platelet activation. A variety of foods, drugs, and
      environmental exposures have been implicated in this condition. CASE REPORT: The
      case involves a 62-year-old woman with dyspnea, chest pain, and transient ST
      segment elevation after ingesting celecoxib. Her symptoms resolved with treatment
      for a suspected allergic reaction. Although she did have mild elevation of serum
      cardiac biomarkers, subsequent cardiac catheterization demonstrated normal
      coronary arteries. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This is
      the first reported case of ST-segment elevation myocardial infarction after
      allergy to celecoxib. Knowledge of Kounis syndrome will better prepare physicians
      in both its identification and clinical management.

PMID- 25989970
TI  - Deficits in learning and memory in mice with a mutation of the candidate dyslexia
      susceptibility gene Dyx1c1.
AB  - Dyslexia is a learning disability characterized by difficulty learning to read
      and write. The underlying biological and genetic etiology remains poorly
      understood. One candidate gene, dyslexia susceptibility 1 candidate 1 (DYX1C1),
      has been shown to be associated with deficits in short-term memory in dyslexic
      populations. The purpose of the current study was to examine the behavioral
      phenotype of a mouse model with a homozygous conditional (forebrain) knockout of
      the rodent homolog Dyx1c1. Twelve Dyx1c1 conditional homozygous knockouts, 7
      Dyx1c1 conditional heterozygous knockouts and 6 wild-type controls were
      behaviorally assessed. Mice with the homozygous Dyx1c1 knockout showed deficits
      on memory and learning, but not on auditory or motor tasks. These findings affirm
      existing evidence that DYX1C1 may play an underlying role in the development of
      neural systems important to learning and memory, and disruption of this function
      could contribute to the learning deficits seen in individuals with dyslexia.

PMID- 25989972
TI  - Next generation sequencing in women affected by nonsyndromic premature ovarian
      failure displays new potential causative genes and mutations.
AB  - OBJECTIVE: To identify new molecular actors involved in nonsyndromic premature
      ovarian failure (POF) etiology. DESIGN: This is a retrospective case-control
      cohort study. SETTING: University research group and IVF medical center.
      PATIENT(S): Twelve women affected by nonsyndromic POF. The control group included
      176 women whose menopause had occurred after age 50 and had no antecedents
      regarding gynecological disease. A further 345 women from the same ethnic origin
      (general population group) were also recruited to assess allele frequency for
      potentially deleterious sequence variants. INTERVENTION(S): Next generation
      sequencing (NGS), Sanger sequencing, and bioinformatics analysis. MAIN OUTCOME
      MEASURE(S): The complete coding regions of 70 candidate genes were massively
      sequenced, via NGS, in POF patients. Bioinformatics and genetics were used to
      confirm NGS results and to identify potential sequence variants related to the
      disease pathogenesis. RESULT(S): We have identified mutations in two novel genes,
      ADAMTS19 and BMPR2, that are potentially related to POF origin. LHCGR mutations,
      which might have contributed to the phenotype, were also detected. CONCLUSION(S):
      We thus recommend NGS as a powerful tool for identifying new molecular actors in
      POF and for future diagnostic/prognostic purposes.

PMID- 25989971
TI  - Widespread disruption of host transcription termination in HSV-1 infection.
AB  - Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for
      virus-induced host shut-off. Here we show that global changes in transcription
      and RNA processing and their impact on translation can be analysed in a single
      experimental setting by applying 4sU-tagging of newly transcribed RNA and
      ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1
      triggers the disruption of transcription termination of cellular, but not viral,
      genes. This results in extensive transcription for tens of thousands of
      nucleotides beyond poly(A) sites and into downstream genes, leading to novel
      intergenic splicing between exons of neighbouring cellular genes. As a
      consequence, hundreds of cellular genes seem to be transcriptionally induced but
      are not translated. In contrast to previous reports, we show that HSV-1 does not
      inhibit co-transcriptional splicing. Our approach thus substantially advances our
      understanding of HSV-1 biology and establishes HSV-1 as a model system for
      studying transcription termination. 

PMID- 25989973
TI  - Effect of menses on standardized assessment of sexual dysfunction among women
      with uterine fibroids: a cohort study.
AB  - OBJECTIVE: To determine if assessment of sexual dysfunction by the Female Sexual
      Function Index (FSFI) is related to whether the FSFI is administered during or
      between menses, in women with symptomatic uterine fibroids. DESIGN: Prospective
      cohort. SETTING: Academic medical centers. PATIENT(S): Premenopausal women who
      had symptomatic uterine fibroids and were enrolled in fibroid treatment trials.
      INTERVENTION(S): Administration of FSFI during and between menses. MAIN OUTCOME
      MEASURE(S): Mean FSFI scores in each of 6 domains, and a discordance score to
      report individual differences in assessment. RESULT(S): Thirty-three women
      completed the FSFI, during menstruation, and at a time in their cycle when they
      were not menstruating. The mean FSFI scores for each domain did not differ based
      on when in the menstrual cycle the instrument was administered. However, on an
      individual level, nearly half of the women reported sexual dysfunction
      differently during menses than between menses. Of those that reported
      differences, the pain and desire domains improved; the lubrication and
      satisfaction domains worsened during menses. CONCLUSION(S): Although the mean
      values of the domain scores were not different, women did report differences in
      sexual functioning during vs. between menses. Timing of the questionnaire in
      relation to menses should be considered in sexual-dysfunction assessment for
      women with uterine fibroids. CLINICAL TRIALS REGISTRATION NUMBER: NCT00995878.

PMID- 25989974
TI  - Are reproductive endocrinologists still gynecologists?

PMID- 25989975
TI  - Introduction: Training in reproductive endocrinology and infertility: meeting
      worldwide needs.
AB  - Training in reproductive endocrinology (REI) and its male variant, andrology, has
      been profoundly influenced by the central role captured by assisted reproductive
      technologies (ART). The marked differences in financial, regulatory, and
      societal/ethical restrictions on ART in different countries of the world also
      prominently influence the clinical management of infertility. Training should
      strive for comprehensive teaching of all medically indicated procedures, even if
      only to optimize cross-border care. Better international standardization of
      infertility practices and training would benefit worldwide infertility care and
      should be promoted by international societies. 

PMID- 25989976
TI  - Autologous endometrial coculture biopsy: is timing everything?
AB  - OBJECTIVE: To determine whether endometrial biopsy timing affects implantation
      rates and pregnancy outcomes in patients undergoing in vitro fertilization (IVF)
      with autologous endometrial coculture (AECC). DESIGN: Retrospective cohort study.
      SETTING: Academic medical center. PATIENT(S): All patients with a history of at
      least one failed IVF cycle who underwent an IVF-AECC cycle at our center from May
      2004 to November 2013 were included. INTERVENTION(S): Patients underwent luteal
      phase endometrial biopsy in preparation for IVF. Biopsy samples were used for IVF
      in either the subsequent menstrual cycle or a future cycle. Embryos were cultured
      in AECC media and transferred on day 3. MAIN OUTCOME MEASURE(S): A total of 2,533
      cycles of 1,719 patients who underwent an IVF-AECC cycle were identified. Cycles
      were stratified by endometrial biopsy timing. Clinical outcomes, including
      implantation, pregnancy, and live birth rates, were analyzed and compared between
      the two groups. RESULT(S): A total of 1,416 coculture biopsies were performed in
      the menstrual cycle before IVF and 1,117 were performed more than one cycle
      before IVF. The two groups were similar in age, body mass index, number of mature
      oocytes retrieved, and best embryo grade. There were no significant differences
      in implantation, clinical pregnancy, or live birth rates, with adjusted relative
      risks of 1.02 (95% confidence interval [CI] 0.92-1.13), 1.02 (95% CI 0.91-1.14),
      and 0.99 (95% CI 0.86-1.16), respectively. CONCLUSION(S): Coculture biopsy in the
      cycle preceding IVF does not increase implantation, clinical pregnancy, or live
      birth rates compared with biopsies performed more than one cycle before IVF.
      Previously demonstrated improvements in embryo quality and pregnancy outcomes in
      patients undergoing IVF with AECC are probably not attributable to biopsy-induced
      endometrial injury.

PMID- 25989977
TI  - Mutational screening of NR5A1 gene encoding steroidogenic factor 1 in
      cryptorchidism and male factor infertility and functional analysis of seven
      undescribed mutations.
AB  - OBJECTIVE: To study the role of NR5A1 in cryptorchidism and male factor
      infertility. Mutations in NR5A1 have been initially associated with primary
      adrenal insufficiency and 46,XY gonadal dysgenesis and more recently with less
      severe phenotypes, including preliminary descriptions in severe forms of male
      factor infertility. Far less clear is the possible involvement of NR5A1 mutations
      in cryptorchidism. DESIGN: Retrospective cross-sectional cohort study and
      functional analysis of mutant proteins. SETTING: University department.
      PATIENT(S): Nine hundred fifty-nine subjects, including children with
      cryptorchidism and adults with different semen phenotypes associated or not
      associated with a history of cryptorchidism. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Mutation screening of NR5A1 by sequencing all exons. Functional
      analysis of mutant proteins by transactivation assays of CYP11A1 and CYP17A1
      promoters. RESULT(S): We identified seven undescribed and one previously
      described missense mutation in subjects with severe spermatogenic impairment,
      without (4/236, 1.7%) and with (3/85, 3.5%) a history of cryptorchidism. Newborns
      with cryptorchidism carry NR5A1 mutations at low frequency (0.7%), whereas no
      mutations were found in milder forms of infertility and normozoospermia,
      irrespective of the presence of cryptorchidism. The mutant proteins showed
      impaired transactivation of gonadal promoters. A single nucleotide polymorphism
      (rs1110061; c.437 G->C; p.Gly146Ala) was also associated with more severe forms
      of spermatogenic impairment with cryptorchidism. CONCLUSION(S): This study,
      combined with what is already known about NR5A1-associated phenotypes, suggests
      considering mutations in this gene as a novel genetic cause of more severe forms
      of male factor infertility, especially when associated with a history of
      cryptorchidism.

PMID- 25989978
TI  - Concordance among sperm deoxyribonucleic acid integrity assays and semen
      parameters.
AB  - OBJECTIVE: To assess the concordance of sperm chromatin structure assay (SCSA)
      results, epifluorescence TUNEL assay results, and standard semen parameters.
      DESIGN: Prospective, observational study. SETTING: Tertiary referral andrology
      clinic. PATIENT(S): A total of 212 men evaluated for subfertility by a single
      physician. INTERVENTION(S): Clinical history, physical examination, semen
      analysis, SCSA, and TUNEL assay. MAIN OUTCOME MEASURE(S): Spearman's rank
      correlation coefficients (r) between SCSA DNA fragmentation index (DFI),
      percentage TUNEL-positive sperm, and semen analysis parameters. RESULT(S): There
      was a positive correlation between SCSA DFI and TUNEL (r = 0.31), but the
      strength of this correlation was weaker than has previously been reported. The
      discordance rate between SCSA and TUNEL in classifying patients as normal or
      abnormal was 86 of 212 (40.6%). The SCSA DFI was moderately negatively correlated
      with sperm concentration and motility. The TUNEL results were unrelated to
      standard semen parameters. CONCLUSION(S): The SCSA DFI and percentage TUNEL
      positive sperm are moderately correlated measures of sperm DNA integrity but
      yield different results in a large percentage of patients. The DFI is well
      correlated with semen analysis parameters, whereas TUNEL is not. These data
      indicate that the SCSA and TUNEL assay measure different aspects of sperm DNA
      integrity and should not be used interchangeably.

PMID- 25989979
TI  - Stro-1/CD44 as putative human myometrial and fibroid stem cell markers.
AB  - OBJECTIVE: To identify and characterize myometrial/fibroid stem cells by specific
      stem cell markers in human myometrium, and to better understand the stem cell
      contribution in the development of uterine fibroids. DESIGN: Prospective,
      experimental human and animal study. SETTING: University research laboratory.
      PATIENT(S)/ANIMAL(S): Women undergoing hysterectomy for treatment of symptomatic
      uterine fibroids and female NOD/SCID/IL-2Rgamma(null) mice. INTERVENTION(S):
      Identification and isolation of stem cells from human fibroids and adjacent
      myometrium tissues using Stro-1/CD44-specific surface markers. MAIN OUTCOME
      MEASURE(S): Flow cytometry, semiquantitative polymerase chain reaction,
      clonogenicity assays, cell culture, molecular analysis, immunocyto
      histochemistry, in vitro differentiation, and xenotransplantation assays.
      RESULT(S): Using Stro-1/CD44 surface markers, we were able to isolate stem cells
      from adjacent myometrium and human fibroid tissues. The undifferentiated status
      of isolated cells was confirmed by the expression of ABCG2 transporter, as well
      as additional stem cell markers OCT4, NANOG, and GDB3, and the low expression of
      steroid receptors ERalpha and PR-A/PR-B. Mesodermal cell origin was established
      by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and
      absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the
      ability of these cells to differentiate in vitro into adipocytes, osteocytes, and
      chondrocytes. Finally, their functional capability to form fibroid-like lesions
      was established in a xenotransplantation mouse model. The injected cells labeled
      with superparamagnetic iron oxide were tracked by both magnetic resonance imaging
      and fluorescence imaging, thus demonstrating the regenerative potential of
      putative fibroid stem cells in vivo. CONCLUSION(S): We have demonstrated that
      Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of
      myometrial/fibroids cells, exhibiting key features of stem/progenitor cells.
      These findings offer a useful tool to better understand the initiation of uterine
      fibroids, and may lead to the establishment of effective therapeutic options.

PMID- 25989982
TI  - Genetic Differentiation of Hypothalamus Parentally Biased Transcripts in
      Populations of the House Mouse Implicate the Prader-Willi Syndrome Imprinted
      Region as a Possible Source of Behavioral Divergence.

PMID- 25989980
TI  - OncoRep: an n-of-1 reporting tool to support genome-guided treatment for breast
      cancer patients using RNA-sequencing.
AB  - BACKGROUND: Breast cancer comprises multiple tumor entities associated with
      different biological features and clinical behaviors, making individualized
      medicine a powerful tool to bring the right drug to the right patient. Next
      generation sequencing of RNA (RNA-Seq) is a suitable method to detect targets for
      individualized treatment. Challenges that arise are i) preprocessing and
      analyzing RNA-Seq data in the n-of-1 setting, ii) extracting clinically relevant
      and actionable targets from complex data, iii) integrating drug databases, and
      iv) reporting results to clinicians in a timely and understandable manner.
      RESULTS: To address these challenges, we present OncoRep, an RNA-Seq based n-of-1
      reporting tool for breast cancer patients. It reports molecular classification,
      altered genes and pathways, gene fusions, clinically actionable mutations and
      drug recommendations. It visualizes the data in an approachable html-based
      interactive report and a PDF clinical report, providing the clinician and tumor
      board with a tool to guide the treatment decision making process. CONCLUSIONS:
      OncoRep is free and open-source ( https://bitbucket.org/sulab/oncorep/ ), thereby
      offering a platform for future development and innovation by the community.

PMID- 25989983
TI  - Phylogeographic Analyses of American Black Bears (Ursus americanus) Suggest Four
      Glacial Refugia and Complex Patterns of Postglacial Admixture.
AB  - Studies of species with continental distributions continue to identify
      intraspecific lineages despite continuous habitat. Lineages may form due to
      isolation by distance, adaptation, divergence across barriers, or genetic drift
      following range expansion. We investigated lineage diversification and admixture
      within American black bears (Ursus americanus) across their range using 22 k
      single nucleotide polymorphisms and mitochondrial DNA sequences. We identified
      three subcontinental nuclear clusters which we further divided into nine
      geographic regions: Alaskan (Alaska-East), eastern (Central Interior Highlands,
      Great Lakes, Northeast, Southeast), and western (Alaska-West, West, Pacific
      Coast, Southwest). We estimated that the western cluster diverged 67 ka, before
      eastern and Alaskan divergence 31 ka; these divergence dates contrasted with
      those from the mitochondrial genome where clades A and B diverged 1.07 Ma, and
      clades A-east and A-west diverged 169 ka. We combined estimates of divergence
      timing with hindcast species distribution models to infer glacial refugia for the
      species in Beringia, Pacific Northwest, Southwest, and Southeast. Our results
      show a complex arrangement of admixture due to expansion out of multiple refugia.
      The delineation of the genomic population clusters was inconsistent with the
      ranges for 16 previously described subspecies. Ranges for U. a. pugnax and U. a.
      cinnamomum were concordant with admixed clusters, calling into question how to
      order taxa below the species level. Additionally, our finding that U. a.
      floridanus has not diverged from U. a. americanus also suggests that morphology
      and genetics should be reanalyzed to assess taxonomic designations relevant to
      the conservation management of the species. 

PMID- 25989984
TI  - Letter to the Editor.

PMID- 25989985
TI  - Corticosteroid or placebo injection combined with deep transverse friction
      massage, Mills manipulation, stretching and eccentric exercise for acute lateral
      epicondylitis: a randomised, controlled trial.
AB  - BACKGROUND: Lateral epicondylitis of the elbow is a frequent condition with long
      lasting symptoms. Corticosteroid injection is increasingly discouraged and there
      is little knowledge on the combined effect of corticosteroid injection and
      physiotherapy for acute conditions. We wanted to investigate the efficacy of
      physiotherapy alone and combined with corticosteroid injection for acute lateral
      epicondylitis. METHODS: A randomized, controlled study with one-year follow-up
      was conducted in a general practice setting in Sarpsborg, Norway. We included 177
      men and women aged 18 to 70 with clinically diagnosed lateral epicondylitis of
      recent onset (2 weeks to 3 months). They were randomly assigned to one of three
      treatments: physiotherapy with two corticosteroid injections, physiotherapy with
      two placebo injections or wait-and-see (control). Physiotherapy consisted of deep
      transverse friction massage, Mills manipulation, stretching, and eccentric
      exercises. We used double blind injection of corticosteroid and single blind
      assessments. The main outcome measure was treatment success defined as patients
      rating themselves completely recovered or much better on a six-point scale.
      RESULTS: One hundred fifty-seven patients (89 %) completed the trial. Placebo
      injection with physiotherapy showed no significant difference compared to control
      or to corticosteroid injection with physiotherapy at any follow-up.
      Corticosteroid injection with physiotherapy had a 10.6 times larger odds for
      success at six weeks (odds ratio 10.60, p < 0.01) compared to control (NNT = 3,
      99 % CI 1.5 to 4.2). At 12 weeks there was no significant difference between
      these groups, but at 26 weeks the odds for success were 91 % lower (OR 0.09, p <
      0.01) compared to control, showing a large negative effect (NNT = 5, 99 % CI 2.1
      to 67.4). At 52 weeks there was no significant difference. Both control and
      placebo injection with physiotherapy showed a gradual increase in success.
      CONCLUSIONS: Acute lateral epicondylitis is a self-limiting condition where 3/4
      of patients recover within 52 weeks. Physiotherapy with deep transverse friction
      massage, Mills manipulation, stretching, and eccentric exercises showed no clear
      benefit, and corticosteroid injection gave no added effect. Corticosteroid
      injections combined with physiotherapy might be considered for patients needing a
      quick improvement, but intermediate (12 to 26 weeks) worsening of symptoms makes
      the treatment difficult to recommend. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT00826462.

PMID- 25989987
TI  - Reflections on 50 years of change.
AB  - In honor of the 50th anniversary of the first nurse practitioner (NP) program in
      the United States, Dr. Loretta Ford offers these reflections on the progress of
      NPs in the past half century. 

PMID- 25989986
TI  - Fast and robust 3D T1 mapping using spiral encoding and steady RF excitation at 7
      T: application to cardiac manganese enhanced MRI (MEMRI) in mice.
AB  - Mapping longitudinal relaxation times in 3D is a promising quantitative and non
      invasive imaging tool to assess cardiac remodeling. Few methods are proposed in
      the literature allowing us to perform 3D T1 mapping. These methods often require
      long scan times and use a low number of 3D images to calculate T1 . In this
      project, a fast 3D T1 mapping method using a stack-of-spirals sampling scheme and
      regular RF pulse excitation at 7 T is presented. This sequence, combined with a
      newly developed fitting procedure, allowed us to quantify T1 of the whole mouse
      heart with a high spatial resolution of 208 * 208 * 315 um(3) in 10-12 min
      acquisition time. The sensitivity of this method for measuring T1 variations was
      demonstrated on mouse hearts after several injections of manganese chloride
      (doses from 25 to 150 umol kg(-1) ). T1 values were measured in vivo in both pre-
      and post-contrast experiments. This protocol was also validated on ischemic mice
      to demonstrate its efficiency to visualize tissue damage induced by a myocardial
      infarction. This study showed that combining spiral gradient shape and steady RF
      excitation enabled fast and robust 3D T1 mapping of the entire heart with a high
      spatial resolution.

PMID- 25989988
TI  - Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it
      from Bowen's disease and seborrheic keratosis.
AB  - Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is
      sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in
      situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To
      date, there has never been a report focusing on dermoscopic features to
      distinguish HAS from BD and SK. We found the following dermoscopic findings to be
      characteristic of HAS: fine black dots/globules (75% of cases) and fine scales
      arranged annularly (100% of cases). In contrast, glomerular vessels, which are
      typically observed in BD, were not seen in any of the four cases. Cerebriform
      appearance and milia-like cysts, which are typically observed in SK, were also
      not seen in any of the four cases. The existence of "scattered fine black
      dots/globules" and "fine scales arranged annularly", and the absence of the
      glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS
      resembles BD or SK clinically, it can be distinguished from these by the
      characteristic dermoscopic features. 

PMID- 25989990
TI  - Chemotherapy for lung cancer: still alive!

PMID- 25989989
TI  - Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by
      epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer:
      evaluation of efficacy and safety.
AB  - OBJECTIVE: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free
      paclitaxel coupled to human albumin without an associated increase in toxicity.
      The neoadjuvant study of primary breast cancer was planned to evaluate tumor
      response and safety of triweekly nanoparticle albumin-bound paclitaxel. METHODS:
      Patients with Stage II/III HER2-negative primary breast cancer received four
      courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w),
      followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600
      mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was
      histologically evaluated. In addition, the clinical response, breast-conserving
      rate and safety of this treatment were monitored. RESULTS: Among 53 patients who
      received nanoparticle albumin-bound paclitaxel followed by epirubicin and
      cyclophosphamide neoadjuvant chemotherapy, pathological complete response and
      near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%)
      patients who had surgery, respectively. The overall objective response rate was
      71.7% after completion of chemotherapy. Based on Positron Emission Tomography
      Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete
      metabolic response and partial metabolic response after 2-3 courses of
      nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most
      common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were
      Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%)
      patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events.
      CONCLUSION: Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound
      paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast
      cancer patients with acceptable clinical response and drug tolerance, but
      conferred a low rate of pathological complete response. Monotherapy with q3w
      nanoparticle albumin-bound paclitaxel could be an appropriate substitute for
      solvent-based taxane in terms of therapeutic and safety management.

PMID- 25989991
TI  - Comparison of garenoxacin with levofloxacin as antimicrobial prophylaxis in acute
      myeloid leukemia.
AB  - OBJECTIVE: Levofloxacin is widely used as antimicrobial prophylaxis against high
      risk chemotherapy-induced neutropenia. Garenoxacin, a fluoroquinolone developed
      in Japan, shows a stronger in vitro antimicrobial activity against Gram-positive
      bacteria than levofloxacin. METHODS: We retrospectively analyzed high-risk
      patients with acute myeloid leukemia who were administered garenoxacin (n = 36)
      or levofloxacin (n = 120) during chemotherapy. We compared the profiles of
      infections between these fluoroquinolones. RESULTS: Febrile events occurred in 31
      (86%) and 93 (78%) cases in the garenoxacin and levofloxacin group, respectively
      (P = 0.35). Bloodstream infections by Gram-positive bacteria were recorded in one
      (3%) case in the garenoxacin group and 25 (21%) cases in the levofloxacin group
      (P < 0.01). In contrast, bloodstream infections by Gram-negative microorganisms
      were identified in five (4%) cases in the levofloxacin group and eight (22%)
      cases in the garenoxacin group (P < 0.01). CONCLUSIONS: These results indicate
      that there may be substantial differences in the antimicrobial spectrum between
      different fluoroquinolones. Although there are several biases due to rather small
      sample size and the retrospective nature, we should take the differences into
      consideration when we administer a prophylactic fluoroquinolone to a patient with
      hematological disease.

PMID- 25989992
TI  - Pharmacotherapy for bipolar depression: comparative efficacy and acceptability is
      in the eye of the beholder.

PMID- 25989993
TI  - NICE recommendations: why no disinvestment recommendations to offset investment
      decisions?

PMID- 25989994
TI  - Oligosaccharides in infant formula: more evidence to validate the role of
      prebiotics.
AB  - The gastrointestinal (GI) microbiota differs between breast-fed and classic
      infant formula-fed infants. Breast milk is rich in prebiotic oligosaccharides
      (OS) and may also contain some probiotics, but scientific societies do not
      recommend the addition of prebiotic OS or probiotics to standard infant formula.
      Nevertheless, many infant formula companies often add one or the other or both.
      Different types of prebiotic OS are used in infant formula, including galacto
      oligosaccharide, fructo-oligosaccharide, polydextrose and mixtures of these OS,
      but none adds human milk OS. There is evidence that the addition of prebiotics to
      infant formula brings the GI microbiota of formula-fed infants closer to that of
      breast-fed infants. Prebiotics change gut metabolic activity (by decreasing stool
      pH and increasing SCFA), have a bifidogenic effect and bring stool consistency
      and defecation frequency closer to those of breast-fed infants. Although there is
      only limited evidence that these changes in GI microbiota induce a significant
      clinical benefit for the immune system, interesting positive trends have been
      observed in some markers. Additionally, adverse effects are extremely seldom.
      Prebiotics are added to infant formula because breast milk contains human milk
      OS. Because most studies suggest a trend of beneficial effects and because these
      ingredients are very safe, prebiotics bring infant formula one step closer to the
      golden standard of breast milk. 

PMID- 25989995
TI  - Contribution of dietary starch to hepatic and systemic carbohydrate fluxes in
      European seabass (Dicentrarchus labrax L.).
AB  - In the present study, the effects of partial substitution of dietary protein by
      digestible starch on endogenous glucose production were evaluated in European
      seabass (Dicentrarchus labrax). The fractional contribution of dietary
      carbohydrates v. gluconeogenesis to blood glucose appearance and hepatic glycogen
      synthesis was quantified in two groups of seabass fed with a diet containing 30%
      digestible starch (DS) or without a carbohydrate supplement as the control
      (CTRL). Measurements were performed by transferring the fish to a tank containing
      water enriched with 5% (2)H2O over the last six feeding days, and quantifying the
      incorporation of (2)H into blood glucose and hepatic glycogen by (2)H NMR. For
      CTRL fish, gluconeogenesis accounted for the majority of circulating glucose
      while for the DS fish, this contribution was significantly lower (CTRL 85 (SEM 4)
      % v. DS 54 (SEM 2) %; P < 0.001). Hepatic glycogen synthesis via gluconeogenesis
      (indirect pathway) was also significantly reduced in the DS fish, in both
      relative (CTRL 100 (SEM 1) % v. DS 72 (SEM 1) %; P < 0.001) and absolute terms
      (CTRL 28 (SEM 1) v. DS 17 (sem 1) MUmol/kg per h; P < 0.001). A major fraction of
      the dietary carbohydrates that contributed to blood glucose appearance (33 (sem
      1) % of the total 47 (SEM 2) %) had undergone exchange with hepatic glucose 6
      phosphate. This indicated the simultaneous activity of hepatic glucokinase and
      glucose 6-phosphatase. In conclusion, supplementation of digestible starch
      resulted in a significant reduction of gluconeogenic contributions to systemic
      glucose appearance and hepatic glycogen synthesis.

PMID- 25989996
TI  - Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for
      ethanol-related glucose intolerance?
AB  - The exact mechanism of ethanol's effects on glucose tolerance has not been well
      determined. The present study focuses for the first time on hypoxia and low-grade
      inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male
      Wistar rats were randomly allocated into control and ethanol feeding groups.
      Ethanol-treated rats received edible ethanol once a day at a total dosage of 5
      g/kg per d, and the controls received distilled water. Ethanol volumes were
      adjusted every week. At the end of 8 weeks, we carried out an oral glucose
      tolerance test. Blood and AT were collected for measuring hypoxia-inducible
      factor-1alpha (HIF-1alpha), GLUT1, TNF-alpha, IL-6, leptin and vascular
      endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9
      adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells
      were then collected for measuring HIF-1alpha, GLUT1, TNF-alpha and IL-6. The
      results showed that long-term ethanol consumption impaired glucose tolerance in
      rats. Ethanol consumption had little influence on body weight, but both
      epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as
      compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the
      protein levels of HIF-1alpha and GLUT1, the indicators of hypoxia in rat
      epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the
      levels of inflammation-related adipokines, such as TNF-alpha, IL-6, leptin and
      VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and
      low-grade inflammation might be a new mechanism in the treatment of ethanol
      related diabetes.

PMID- 25989997
TI  - Higher serum 25-hydroxyvitamin D concentrations are related to a reduced risk of
      depression.
AB  - Vitamin D has been suggested to protect against depression, but epidemiological
      evidence is scarce. The present study investigated the relationship of serum 25
      hydroxyvitamin D (25(OH)D) with the prevalence of depressive and anxiety
      disorders. The study population consisted of a representative sample of Finnish
      men and women aged 30-79 years from the Health 2000 Survey. The sample included
      5371 individuals, of which 354 were diagnosed with depressive disorder and 222
      with anxiety disorder. Serum 25(OH)D concentration was determined from frozen
      samples. In a cross-sectional study, a total of four indicators of depression and
      one indicator of anxiety were used as dependent variables. Serum 25(OH)D was the
      risk factor of interest, and logistic models used further included
      sociodemographic and lifestyle variables as well as indicators of metabolic
      health as confounding and/or effect-modifying factors. The population
      attributable fraction (PAF) was estimated. Individuals with higher serum 25(OH)D
      concentrations showed a reduced risk of depression. The relative odds between the
      highest and lowest quartiles was 0.65 (95% CI 0.46, 0.93; P for trend = 0.006)
      after adjustment for sociodemographic, lifestyle and metabolic factors. Higher
      serum 25(OH)D concentrations were associated with a lower prevalence of
      depressive disorder especially among men, younger, divorced and those who had an
      unhealthy lifestyle or suffered from the metabolic syndrome. The PAF was
      estimated to be 19% for depression when serum 25(OH)D concentration was at least
      50 nmol/l. These results support the hypothesis that higher serum 25(OH)D
      concentrations protect against depression even after adjustment for a large
      number of sociodemographic, lifestyle and metabolic factors. Large-scale
      prospective studies are needed to confirm this finding.

PMID- 25989998
TI  - Contents of total fat, fatty acids, starch, sugars and dietary fibre in Swedish
      market basket diets.
AB  - The typical dietary supply of total fat, fatty acids, starch, sugars, polyols and
      dietary fibre in Sweden was assessed from analyses of market baskets (MB)
      purchased in 2005 and 2010. MB were based on food balance sheets, with each
      basket comprising about 130 foods, which represented more than 90% of annual
      dietary supply. Foods were divided into ten to twelve categories. In 2010, total
      fat contributed 34% of energy (E%), SFA 14.3 E%, MUFA 12.8 E%, PUFA 4.6 E%, n-6
      fatty acids 3.6 E%, n-3 fatty acids 1.0 E% and trans-fatty acids (TFA) 0.5 E%.
      Glycaemic carbohydrates contributed 47 E%, monosaccharides 9 E%, sucrose 11 E%,
      disaccharides 15 E% and total sugars 24 E%. Added sugars contributed about 15 E%.
      Dietary fibre content was about 1.7 g/MJ in the 2010 MB. Compared with the 2005
      MB, the dietary supply of TFA and dietary fibre was lower, otherwise differences
      were small. The present MB survey shows that the content of SFA and added sugars
      was higher than the current Nordic Nutrition Recommendations, while the content
      of PUFA and especially dietary fibre was lower. TFA levels decreased and dietary
      supply was well below the recommendations of the WHO. These results emphasise a
      focus on quality and food sources of fat and carbohydrates, limiting foods rich
      in SFA and added sugars and replacing them with foods rich in dietary fibre and
      cis-unsaturated fatty acids.

PMID- 25989999
TI  - Relaxation NMR as a tool to study the dispersion and formulation behavior of
      nanostructured carbon materials.
AB  - Solvent relaxation NMR has been used to estimate the surface areas and
      wettability of various types of nanostructured carbon materials in a range of
      solvents including water, ethanol, and tetrahydrofuran. We illustrate the
      application of the technique through several short case studies using samples
      including nanocarbon blacks, graphene oxide, nanographites, and porous graphenes.
      The technique is shown to give a good measure of surface area, correlating well
      with conventional surface area estimates obtained by nitrogen adsorption,
      transmission electron microscopy, or light scattering for the non-porous samples.
      NMR relaxation has advantages in terms of speed of analysis and being able to use
      concentrated, wet, and opaque samples. For samples that are porous, two distinct
      surface areas can be estimated assuming the two environments ('inner' and
      'outer') have the same surface chemistry, and that there is a slow exchange of
      solvent molecules between them. Furthermore, we show that differences in
      wettability and dispersability between samples dispersed in water, ethanol, and
      cyclopentanone can be observed, along with changes to the surface chemistry of
      the interface. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25990000
TI  - Thermoresponsive PNIPAM Coatings on Nanostructured Gratings for Cell Alignment
      and Release.
AB  - Thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) has been widely used as a
      surface coating to thermally control the detachment of adsorbed cells without the
      need for extreme stimuli such as enzyme treatment. Recently, the use of 2D and 3D
      scaffolds in controlling cell positioning, growth, spreading, and migration has
      been of a great interest in tissue engineering and cell biology. Here, we use a
      PNIPAM polymer surface coating atop a nanostructured linear diffraction grating
      to controllably change the surface topography of 2D linear structures using
      temperature stimuli. Neutron reflectometry and surface diffraction are utilized
      to examine the conformity of the polymer coating to the grating surface, its
      hydration profile, and its evolution in response to temperature variations. The
      results show that, in the collapsed state, the PNIPAM coating conforms to the
      grating structures and retains a uniform hydration of 63%. In the swollen state,
      the polymer expands beyond the grating channels and absorbs up to 87% water. Such
      properties are particularly desirable for 2D cell growth scaffolds with a built
      in nonextreme tissue-release mechanism. Indeed, the current system demonstrates
      advanced performance in the effective alignment of cultured fibroblast cells and
      the easy release of the cells upon temperature change. 

PMID- 25990001
TI  - Contribution of two conserved histidines to the dual activity of archaeal RNA
      guide-dependent and -independent pseudouridine synthase Cbf5.
AB  - In all organisms, several distinct stand-alone pseudouridine synthase (PUS)
      family enzymes are expressed to isomerize uridine into pseudouridine (Psi) by
      specific recognition of RNAs. In addition, Psis are generated in Archaea and
      Eukaryotes by PUS enzymes which are organized as ribonucleoprotein particles
      (RNP)--the box H/ACA s/snoRNPs. For this modification system, a unique TruB-like
      catalytic PUS subunit is associated with various RNA guides which specifically
      target and secure substrate RNAs by base-pairing. The archaeal Cbf5 PUS displays
      the special feature of exhibiting both RNA guide-dependent and -independent
      activities. Structures of substrate-bound TruB and H/ACA sRNP revealed the
      importance of histidines in positioning the target uridine in the active site. To
      analyze the respective role of H60 and H77, we have generated variants carrying
      alanine substitutions at these positions. The impact of the mutations was
      analyzed for unguided modifications U(55) in tRNA and U2603 in 23S rRNA, and for
      activity of the box H/ACA Pab91 sRNP enzyme. H77 (H43 in TruB), but not H60,
      appeared to be crucial for the RNA guide-independent activity. In contrast to
      earlier suggestions, H60 was found to be noncritical for the activity of the
      H/ACA sRNP, but contributes together with H77 to the full activity of H/ACA
      sRNPs. The data suggest that a similar catalytic process was conserved in the two
      divergent pseudouridylation systems.

PMID- 25990002
TI  - Choroidal abnormalities in neurofibromatosis type 1 detected by near-infrared
      reflectance imaging in paediatric population.
AB  - PURPOSE: To investigate choroidal abnormalities in paediatric patients with
      neurofibromatosis type 1 (NF1) detected by near-infrared reflectance (NIR)
      retinography in order to evaluate diagnostic accuracy. METHODS: Seventy-eight
      paediatric patients with NF1, diagnosed according to the National Institutes of
      Health (NIH) criteria, and 96 healthy control subjects matched for age were
      examined. Enrolled patients were under 16 years old. The presence of choroidal
      abnormalities was investigated by confocal scanning laser ophthalmoscopy. Main
      outcome measure was to evaluate diagnostic accuracy in paediatric patients
      compared with the NIH criteria. RESULTS: Seventy-eight patients with NF1 (41
      female, 37 male; mean age 8.1 +/- 3.5 years) were compared with 96 healthy
      control subjects (42 female, 54 male; mean age 8 +/- 3 years). Choroidal
      abnormalities were observed in 54 (69.2%) of the patients with NF1. As regards
      the fundus topographical distribution, choroidal abnormalities were more frequent
      at the posterior pole with a statistically significant correlation between
      patient age and the number of involved choroidal areas (Spearman r = 0.23; p <
      0.04). No choroidal abnormalities were present in the control group. Detection
      accuracy of choroidal nodules was 70%. CONCLUSION: Choroidal abnormalities
      appearing as bright patchy regions detected by NIR imaging occurred very
      frequently in paediatric patients affected by NF1. The present study appears to
      show that NIR used to detect choroidal involvement allows for elevated diagnostic
      accuracy.

PMID- 25990003
TI  - Hypothesis: Human papillomavirus vaccination syndrome--small fiber neuropathy and
      dysautonomia could be its underlying pathogenesis.
AB  - Vaccination has been one of the most effective public health measures in the
      history of medicine. However, seemingly inexplicit adverse reactions have been
      described after the injection of the newer vaccines vs. human papillomavirus
      (HPV). The symptoms more often reported are chronic pain with paresthesias,
      headaches, fatigue, and orthostatic intolerance. Adverse reactions appear to be
      more frequent after HPV vaccination when compared to other type of immunizations.
      Different isolated cases and small series have described the development of
      complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome
      (POTS), and fibromyalgia after HPV vaccination. These are illnesses often
      difficult to diagnose that have overlapping clinical features. Sympathetic
      nervous system dysfunction seems to play a major role in the pathogenesis of
      these syndromes. Also, small fiber neuropathy has been recently recognized in
      CRPS, POTS, and fibromyalgia. This article forwards the hypothesis that small
      fiber neuropathy and dysautonomia could be the common underlying pathogenesis to
      the group of rare, but severe reactions that follow HPV vaccination. Clinicians
      should be aware of the possible association between HPV vaccination and the
      development of these difficult to diagnose painful dysautonomic syndromes. 

PMID- 25990004
TI  - The age-risk relationship of hematologic malignancies in patients with rheumatoid
      arthritis: a nationwide retrospective cohort study.
AB  - The risk of hematologic malignancies in rheumatoid arthritis (RA) patients has
      been an important clinical concern. The information of age effect on the interval
      from the diagnosis of RA to that of hematologic malignancies is limited. This
      study aimed to define the age-risk relationship between hematologic malignancies
      and RA. A retrospective cohort study was conducted nationwide with 17,472
      patients and 87,360 controls from the Taiwan National Health Insurance Database
      covering 1997-2008. The subsequent development of hematologic malignancy was
      observed. The age-adjusted standardized incidence ratios (SIRs), incidence per
      1000 person-years, follow-up duration for the diagnosis of hematologic
      malignancies, and cumulative hazard rates of hematologic malignancies between RA
      and controls were analyzed. Significantly higher incidences of both lymphoid and
      myeloid malignancies were found in male RA patients compared with RA-free
      patients (SIR 3.36, 95% CI = 2.03-5.57, and SIR: 3.69, 95% CI = 2.46-5.53). A
      significantly increased overall incidence risk was found in lymphoid malignancies
      (SIR 3.00, 95% CI = 2.22-4.05) but not significantly increased in myeloid
      malignancies (SIR 1.54, 95% CI = 0.95-2.50) in female RA. The follow-up duration
      for hematologic malignancies was significantly shorter in RA patients than in RA
      free patients in both males and females (70.70 vs. 103.80 months and 67.73 vs.
      100.93 months, respectively). Additionally, higher cumulative hazard rates in
      both lymphoid and myeloid malignancies were found in male RA patients (p <
      0.0001). RA patients have a shorter incubation time to hematological malignancies
      while comparing to the RA-free people, and the risks are variable in gender and
      different age groups.

PMID- 25990005
TI  - Predictors of response to TNF-alpha antagonist therapy in Chinese rheumatoid
      arthritis.
AB  - This study aimed to investigate the clinical, immunological, and radiologic
      predictors of response to tumor necrosis factor (TNF)-alpha antagonist therapy in
      Chinese rheumatoid arthritis (RA). Ninety RA patients were divided into two
      groups according to their responsiveness to TNF-alpha antagonist therapy at 1
      month: group A (responders) and group B (non-responders). After 3 months of
      therapy, all the 90 patients were re-assessed and re-divided into another two
      groups: group C (responders) and group D (non-responders). Serum samples and
      clinical characteristics as well as radiographic features were collected at
      baseline, first month, and third month post-initial administration of TNF-alpha
      antagonist. Serum TNF-alpha, interleukin (IL)-6, IL-8, IL-34, and matrix
      metalloproteinase (MMP)-3 were measured by enzyme-linked immunosorbent assay
      (ELISA). Disease activity and Sharp score were evaluated. (1) Comparisons between
      groups A and B: subjects in group A showed a lower level of erythrocyte
      sedimentation rate (ESR) and a higher level of albumin (ALB) at baseline than
      that of group B (p < 0.05). The cutoff value of ALB for prediction was >=34.9 g/l
      and that of ESR was <=55.5 mm/h. (2) Comparisons between groups C and D: group C
      showed lower levels of ESR, health assessment questionnaire (HAQ), and IL-34 at
      baseline (p < 0.05). The threshold for prediction were as follows: ESR <=60 mm/h,
      HAQ <=1.3125, and IL-34 <=194.12 pg/ml. (3) The serum cytokines were positively
      correlated with C-reactive protein (CRP) and disease activity index, while ALB
      was negatively correlated with CRP and disease activity. Baseline ALB >=34.9 g/l
      or ESR <=55.5 mm/h might predict a good response at 1-month treatment of TNF
      alpha antagonist, while baseline ESR <=60 mm/h, HAQ <=1.3125, and IL-34 <=194.12
      pg/ml might predict a good response at 3-month treatment.

PMID- 25990006
TI  - Weight loss and undernutrition in community-dwelling patients with Alzheimer's
      dementia: From population based studies to clinical management.
AB  - Weight loss and undernutrition are commonly described in patients with
      Alzheimer's disease (AD) and have been associated with various adverse outcomes.
      Therefore, it is important to know what the best approach is to community
      dwelling AD patients with a risk of developing a poor nutritional status;
      however, there is currently no evidence on which to base nutritional
      recommendations. Expert based recommendations are that the nutritional status
      should be part of the work-up of all AD patients. If weight loss of 5% or more
      has occurred in 3-6 months or if the mini-nutritional assessment (MNA) classifies
      a patient as undernourished, a nutritional intervention should be started. The
      intervention should be multifactorial and encompass treatment of the underlying
      proposed causes and risk factors of weight loss and undernutrition as well as
      improvement of the nutritional status by increasing energy and protein intake
      combined with daily physical activity.

PMID- 25990007
TI  - Impact of joint contracture on older persons in a geriatric setting: A cross
      sectional study.
AB  - BACKGROUND: Joint contractures are a common phenomenon in older persons and are
      assessed by measuring the range of motion; however, little is known about the
      impact of joint contractures on activities of daily living (ADL). OBJECTIVES: The
      aim of the study was to identify problems related to joint contracture of older
      persons in a geriatric setting using the international classification of
      functioning, disability and health (ICF) as a framework. MATERIAL AND METHODS: A
      cross-sectional study was conducted between February and July 2013 in nursing
      homes (n=11) and geriatric rehabilitation hospitals (n=3) in North Rhine
      Westphalia, Germany. The study population included persons aged >=65 years with
      at least one diagnosis of joint contracture. If the participant was unable to
      adequately answer the best informed next of kin or staff nurse acted as a proxy.
      A questionnaire with 124 ICF categories was completed through face-to-face
      interviews with the participants. RESULTS: A total of 149 participants were
      included in the study. The mean age was 77.6+/-6.9 years and 69.8% were women.
      Problems in climbing (94.0%), walking long distances (92.6%) and kneeling (92.6%)
      were most frequently identified. The most often identified facilitators in
      environmental factors were health services, systems and policies (93.2%), whereas
      the leading barrier was climate (30.3%). CONCLUSION: Joint contractures have a
      huge impact on functioning and social participation and particularly on personal
      mobility. From the nursing and rehabilitation perspective, assessments should not
      only measure joint mobility but also determine and quantify the consequences of
      contractures on ADL.

PMID- 25990008
TI  - Serological survey using ELISA to determine the prevalence of Coxiella burnetii
      infection (Q fever) in sheep and goats in Great Britain.
AB  - A survey of Coxiella burnetii infection (Q fever) in sheep flocks and goat herds
      in Great Britain was undertaken. A total of 5791 sheep (384 flocks) and 522 goats
      (145 herds) were examined for C. burnetii antibodies using an ELISA. Overall, 53
      sheep (37 flocks), and four goats (four herds), tested positive. Estimates of
      individual animal, between-flock/-herd and within-flock/-herd crude prevalences
      were 0.9%, 10.2% and 9.0%, respectively, for sheep, and 0.8%, 3% and 26.3%,
      respectively, for goats. With sheep, the likelihood of an animal testing positive
      increased with total flock size (P = 0.002) and number of breeding ewes in the
      flock (P = 0.021). It also increased with number of goats within a 10 km radius
      (P = 0.038). There was no evidence for spatial clustering of positive herds above
      that expected by chance alone. No analysis of risk factors was attempted for
      goats because of the paucity of positives.

PMID- 25990009
TI  - "Tinkle Tinkle Little Girl, How We Wonder Why You Can't": An Unusual AIDP-like
      Syndrome in a Toddler.

PMID- 25990011
TI  - Reply.

PMID- 25990010
TI  - Profiling of relaxin and its receptor proteins in boar reproductive tissues and
      spermatozoa.
AB  - BACKGROUND: Relaxin levels in seminal plasma have been associated with positive
      effects on sperm motility and quality, and thus having potential roles in male
      fertility. However, the origin of seminal relaxin, within the male reproductive
      tract, and the moment of its release in the vicinity of spermatozoa remain
      unclear. Here, we assessed the longitudinal distribution of relaxin and its
      receptors RXFP1 and RXFP2 in the reproductive tract, sex accessory glands, and
      spermatozoa of adult boars. METHODS: Spermatozoa were harvested from three
      fertile boars and reproductive tract (testes and epididymis) and sex accessory
      gland (prostate and seminal vesicles) tissues were collected post-mortem from
      each boar. Epididymis ducts were sectioned into caput, corpus, and cauda regions,
      and spermatozoa were mechanically collected. All samples were subjected to
      immunofluorescence and/or western immunoblotting for relaxin, RXFP1, and RXFP2
      detection. Immunolabeled-spermatozoa were submitted to flow cytometry analyses
      and data were statistically analyzed with ANOVA. RESULTS: Both receptors were
      detected in all tissues, with a predominance of mature and immature isoforms of
      RXFP1 and RXFP2, respectively. Relaxin signals were found in the testes, with
      Leydig cells displaying the highest intensity compared to other testicular cells.
      The testicular immunofluorescence intensity of relaxin was greater than that of
      other tissues. Epithelial basal cells exhibited the highest relaxin
      immunofluorescence intensity within the epididymis and the vas deferens. The
      luminal immunoreactivity to relaxin was detected in the seminiferous tubule,
      epididymis, and vas deferens ducts. Epididymal and ejaculated spermatozoa were
      immunopositive to relaxin, RXFP1, and RXFP2, and epididymal corpus-derived
      spermatozoa had the highest immunoreactivities across epididymal sections. Both
      vas deferens-collected and ejaculated spermatozoa displayed comparable, but
      lowest immunofluorescence signals among groups. The entire sperm length was
      immunopositive to both relaxin and receptors, with relaxin signal being robust in
      the acrosome area and RXFP2, homogeneously distributed than RXFP1 on the head of
      ejaculated spermatozoa. CONCLUSIONS: Immunolocalization indicates that relaxin
      receptor complexes may have important roles in boar reproduction and that
      spermatozoa are already exposed to relaxin upon their production. The findings
      suggest autocrine and/or paracrine actions of relaxin on spermatozoa, either
      before or after ejaculation, which have possible roles on the fertilizing
      potential of spermatozoa.

PMID- 25990012
TI  - Efficacy of adsorbents (bentonite and diatomaceous earth) and turmeric (Curcuma
      longa) in alleviating the toxic effects of aflatoxin in chicks.
AB  - A study was conducted to determine the efficacy of bentonite clay (BC),
      diatomaceous earth (DE) and turmeric powder (TUM) in alleviating the toxic
      effects of aflatoxin B1 (AFB1). A total of 250 Ross-308 d-old male broiler chicks
      were assigned to 10 dietary treatments (5 replicates of 5 chicks) from hatch to d
      21. Dietary treatments were: basal diet; basal diet plus AFB1 (2 mg) or BC
      (0.75%), or DE (0.75%), or TUM (200 mg/kg curcuminoids) and different
      combinations of AFB1, BC, DE and TUM. Feed intake (FI), body weight gain (BWG)
      and feed gain (FG) of the birds fed on BC or DE separately were not different
      from control birds. Birds fed on TUM only had similar FI and FG but lower BWG
      than control chicks. Aflatoxin B1 reduced FI, BWG and serum concentrations of
      glucose, albumin, total protein calcium, but increased FG and relative liver and
      kidney weights. Chicks fed on the combination of AFB1 and BC had similar FI and
      FG to control chicks. Chicks fed on the combination of DE and AFB1 had lower FI
      (23.1%) and BWG (28.6%) compared with control chicks. Chicks fed on the
      combination of TUM and AFB1 also had decreased FI (26.2 %) and BWG (31%) compared
      with control chicks. Chicks fed on the combination of AFB1, BC and TUM consumed
      significantly higher amounts of feed compared with chicks fed on only AF, but
      gained less when compared with control diet chicks. Chicks fed on the combination
      of AFB1, DE and TUM diet had poorer growth performance than those fed on AFB1
      alone. None of the combination diets reduced the severity of liver lesions. 

PMID- 25990014
TI  - PCSK9 inhibitors for LDL lowering.

PMID- 25990013
TI  - Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient
      level pooled analysis of prospectively adjudicated cardiovascular events.
AB  - BACKGROUND: The cardiovascular (CV) safety of linagliptin was evaluated in
      subjects with type 2 diabetes (T2DM). METHODS: Pre-specified patient-level pooled
      analysis of all available double-blind, randomized, controlled trials, >= 12
      weeks' duration (19 trials, 9459 subjects) of linagliptin versus placebo/active
      treatment. Primary end point: composite of prospectively adjudicated CV death,
      non-fatal myocardial infarction, non-fatal stroke, and hospitalization for
      unstable angina (4P-MACE). Hospitalization for congestive heart failure (CHF) was
      also evaluated; adjudication of CHF was introduced during the phase 3 program (8
      trials; 3314 subjects). 4P-MACE was assessed in placebo-controlled trials
      (subgroup of 18 trials; 7746 subjects). Investigator-reported events suggestive
      of CHF from 24 placebo-controlled trials (including trials <12 weeks' duration,
      8778 subjects) were also analyzed. RESULTS: 5847 patients received linagliptin (5
      mg: 5687, 10 mg: 160) and 3612 comparator (glimepiride: 775, voglibose: 162,
      placebo: 2675); cumulative exposure, 4421.3 and 3254.7 patient-years,
      respectively. 4P-MACE incidence rates: 13.4 per 1000 patient-years, linagliptin
      (60 events), 18.9, total comparators (62 events); overall hazard ratio (HR), 0.78
      (95% confidence interval [CI], 0.55-1.12). HR for adjudicated hospitalization for
      CHF (n = 21): 1.04 (0.43-2.47). For placebo-controlled trials, 4P-MACE incidence
      rates: 14.9 per 1000 patient-years, linagliptin (43 events), 16.4, total
      comparators (29 events); overall HR, 1.09 (95% CI, 0.68-1.75). Occurrence of
      investigator-reported events suggestive of CHF was low for linagliptin- (26
      events, 0.5%; serious: 16 events, 0.3%) and placebo-treated (8 events, 0.2%;
      serious: 6 events, 0.2%) patients. CONCLUSIONS: Linagliptin is not associated
      with increased CV risk versus pooled active comparators or placebo in patients
      with T2DM.

PMID- 25990015
TI  - Improving in-kennel presentation of shelter dogs through response-dependent and
      response-independent treat delivery.
AB  - In a sequence of studies, we evaluated 2 behavioral interventions designed to
      decrease undesirable in-kennel behaviors of shelter dogs. In Experiment 1, we
      compared the efficacy of a simple pairing of person with food (response
      independent treat delivery) to an increasing interval differential-reinforcement
      of-other-behavior (DRO) procedure and a control condition. Both procedures
      decreased the median percentage of undesirable behavior from baseline (88.13%,
      interquartile range [IQR] = 52.78% and 66.43%, IQR = 89.06% respectively), and
      the control condition increased behavior by 15.13% (IQR = 32.08%), H(2) = 6.49, p
      = .039. In Experiment 2, we assessed the efficacy of a response-independent
      procedure on the whole shelter population. We found a 68% decrease from baseline
      in the number of dogs that behaved undesirably (U = -4.16, p < .001). Our results
      suggest that a response-independent procedure is equivalent in efficacy to a DRO
      procedure to decrease undesirable in-kennel behavior of shelter dogs. 

PMID- 25990016
TI  - Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of
      neuromyelitis optica.
AB  - INTRODUCTION: Neuromyelitis Optica (NMO) is an autoimmune disease primarily
      targeting the spinal cord and optic nerve leading to paralysis and blindness. The
      discovery of an antibody against the astrocytic water channel, aquaporin-4
      (AQP4), in the majority of patients, has led to the presumption that the antibody
      was necessary for disease pathogenesis. The potential role of T cells in the
      central nervous system, however, has not been thoroughly examined. RESULTS: We
      generated an anti-AQP4 antibody seronegative model of NMO using pathogenic AQP4
      reactive T cells in mice by immunizing AQP4 null mice with peptides corresponding
      to the second extracellular loop of AQP4, loop C. When polarized to a Th17
      phenotype and transferred to wild-type mice, these cells caused tail and limb
      weakness. Histology showed demyelination and T cell infiltration in the spinal
      cord, optic nerve and brain. Animals receiving cells re-stimulated in culture
      with non-specific proteins resulted in no behavioral disease, indicating that
      specific targeting of AQP4 is essential for this phenotype. CONCLUSIONS: In
      summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like
      disease in mice, independent of antibodies, indicating that pathogenic AQP4
      reactive T cells may play a similar role in humans.

PMID- 25990017
TI  - Novel echocardiographic techniques for the evaluation of athletes' heart: A focus
      on speckle-tracking echocardiography.
AB  - BACKGROUND: The development and rapid dissemination of two-dimensional
      echocardiography led to important further advances in our understanding of
      athletes' heart that has been the subject of several echocardiographic studies
      involving many thousands of athletes. The description of ventricular chamber
      enlargement, myocardial hypertrophy and atrial dilatation has led to a more
      comprehensive understanding of cardiac adaptation to exercise conditioning. Most
      recently, advanced echocardiographic techniques have begun to clarify significant
      functional adaptations of the myocardium that accompany previously reported
      morphological features of athletes' heart. In particular, speckle-tracking
      echocardiography (STE) has recently provided further insights into the
      characterisation of myocardial properties. DISCUSSION: STE is a relatively new,
      largely angle-independent, non-invasive imaging technique that allows for an
      objective and quantitative evaluation of global and regional myocardial function.
      STE has enhanced our understanding of athletes' heart through a comprehensive
      characterisation of biventricular and biatrial function, providing novel insights
      into the investigation of physiological adaptation of the heart to exercise
      conditioning. These peculiarities can provide further useful data to distinguish
      between athletes' heart and cardiomyopathies. Furthermore, STE represents a
      promising tool to address new concerns on right ventricular function and to
      increase understanding of the complexity of the non-systemic circulation,
      especially in the athletic population. CONCLUSION: This review article analyses
      new data on cardiac function in athletes by novel echocardiographic techniques
      with a particular attention to the application of STE to characterise
      biventricular and biatrial function in athletes.

PMID- 25990018
TI  - Analysis of the performance of the CHESHIRE and YAPP methods at CASD-NMR round 3.
AB  - We present an analysis of the results obtained at CASD-NMR round 3 by the
      CHESHIRE and the YAPP methods. To determine protein structures, the CHESHIRE
      method uses solely information provided by NMR chemical shifts, while the YAPP
      method uses an automated assignment of NOESY spectra. Of the ten targets of CASD
      NMR round 3, nine CHESHIRE predictions and eight YAPP ones were submitted. The
      eight YAPP predictions ranged from 0.7 to 1.9 A Calpha accuracy, with an average
      of 1.3 A. The nine CHESHIRE predictions ranged from 0.8 to 2.6 A Calpha accuracy
      for the ordered regions of the proteins, with an average of 1.6 A. Taken
      together, these results illustrate how the NOESY based YAPP method and the
      chemical shift based CHESHIRE method can provide structures of comparable
      quality. 

PMID- 25990020
TI  - Computational Study of Catalytic Reaction of Quercetin 2,4-Dioxygenase.
AB  - We present a quantum mechanics/molecular mechanics (QM/MM) and QM-only study on
      the oxidative ring-cleaving reaction of quercetin catalyzed by quercetin 2,4
      dioxygenase (2,4-QD). 2,4-QD has a mononuclear type 2 copper center and
      incorporates two oxygen atoms at C2 and C4 positions of the substrate. It has not
      been clear whether dioxygen reacts with a copper ion or a substrate radical as
      the first step. We have found that dioxygen is more likely to bind to a Cu(2+)
      ion, involving the dissociation of the substrate from the copper ion. Then a
      Cu(2+)-alkylperoxo complex can be generated. Comparison of geometry and stability
      between QM-only and QM/MM results strongly indicates that steric effects of the
      protein environment contribute to maintain the orientation of the substrate
      dissociated from the copper center. The present QM/MM results also highlight that
      a prior rearrangement of the Cu(2+)-alkylperoxo complex and a subsequent hydrogen
      bond switching assisted by the movement of Glu73 can facilitate formation of an
      endoperoxide intermediate selectively. 

PMID- 25990019
TI  - Fractional enrichment of proteins using [2-(13)C]-glycerol as the carbon source
      facilitates measurement of excited state 13Calpha chemical shifts with improved
      sensitivity.
AB  - A selective isotope labeling scheme based on the utilization of [2-(13)C]
      glycerol as the carbon source during protein overexpression has been evaluated
      for the measurement of excited state (13)Calpha chemical shifts using Carr
      Purcell-Meiboom-Gill (CPMG) relaxation dispersion (RD) experiments. As expected,
      the fractional incorporation of label at the Calpha positions is increased two
      fold relative to labeling schemes based on [2-(13)C]-glucose, effectively
      doubling the sensitivity of NMR experiments. Applications to a binding reaction
      involving an SH3 domain from the protein Abp1p and a peptide from the protein
      Ark1p establish that accurate excited state (13)Calpha chemical shifts can be
      obtained from RD experiments, with errors on the order of 0.06 ppm for exchange
      rates ranging from 100 to 1000 s(-1), despite the small fraction of (13)Calpha
      (13)Cbeta spin-pairs that are present for many residue types. The labeling
      approach described here should thus be attractive for studies of exchanging
      systems using (13)Calpha spin probes.

PMID- 25990021
TI  - Metal-organic framework nodes as nearly ideal supports for molecular catalysts:
      NU-1000- and UiO-66-supported iridium complexes.
AB  - Metal-organic frameworks with Zr6 nodes, UiO-66 and NU-1000, were investigated as
      supports for Ir(CO)2 and Ir(C2H4)2 complexes. A single bonding site for the
      iridium is identified on the nodes of NU-1000, whereas two sites are identified
      on UiO-66, although at low iridium loadings only one site is occupied. Density
      functional theory calculations provide structural results that are in good
      agreement with infrared and X-ray absorption fine-structure spectra. The
      reactivity of node-supported Ir(CO)2 with C2H4 and the catalytic activity and
      selectivity of the species initially present as Ir(C2H4)2 for ethylene
      hydrogenation and dimerization were investigated both experimentally and
      computationally and shown to be strongly influenced by the node. 

PMID- 25990022
TI  - Spinal cord protection in open- and endovascular thoracoabdominal aortic aneurysm
      repair: critical review of current concepts and future perspectives.
AB  - Unresolved for over half a century now since the beginning of aortic surgery
      spinal cord injury (SCI) remains the most devastating complication after
      extensive open and endovascular thoracoabdominal aortic aneurysm (TAA/A) repair.
      Over the past decade extensive research on spinal cord perfusion lead to a better
      understanding of previously unknown physiologic mechanisms involved in the
      suspension of the cord's arterial supply and the consecutive development of SCI
      underscoring the need for new concepts in treatment strategy and monitoring
      methods during and after TAA/A repair. Based on this knowledge, new treatment
      strategies in particular the staged-repair were developed. The first-in-man
      translation of this idea has just been published introducing the new concept:
      minimally invasive selective segmental artery coil-embolization. Another approach
      to overcome the most critical initial period after segmental artery occlusion due
      to stent graft deployment in the descending or thoracoabdominal aorta is
      temporary aneurysm sac perfusion, which also has recently been clinically
      trialed. Furthermore, the new non-invasive real-time monitoring method to record
      spinal cord viability by means of near-infrared spectroscopy of the paraspinal
      collateral network by means of near-infrared spectroscopy has also been suggested
      and successfully introduced in a pilot series to a clinical setting. This review
      addresses problems, unsolved questions and future perspectives regarding these
      three new concepts. 

PMID- 25990024
TI  - The 2014 Varsity Medical Ethics Debate: should we allow genetic information to be
      patented?
AB  - The 2014 Varsity Medical Ethics debate convened upon the motion: "This house
      believes that genetic information should not be commoditised". This annual debate
      between students from the Universities of Oxford and Cambridge, now in its sixth
      year, provided the starting point for arguments on the subject. The present
      article brings together and extends many of the arguments put forward during the
      debate. We explore the circumstances under which genetic material should be
      considered patentable, the possible effects of this on the research and
      development of novel therapeutics, and the need for clear guidelines within this
      rapidly developing field.The Varsity Medical Debate was first held in 2008 with
      the aim of allowing students to engage in discussion about ethics and policy
      within healthcare. Two Oxford medical students, Mahiben Maruthappu and Sanjay
      Budheo founded the event. The event is held annually and it is hoped that this
      will allow future leaders to voice a perspective on the arguments behind topics
      that will feature heavily in future healthcare and science policy. This year the
      Oxford University Medical Society at the Oxford Union hosted the debate.

PMID- 25990023
TI  - Assessment of the effector function of CMV-specific CTLs isolated using MHC
      multimers from granulocyte-colony stimulating factor mobilized peripheral blood.
AB  - BACKGROUND: Adoptive transfer of CMV-specific T cells has shown promising results
      in preventing pathological effects caused by opportunistic CMV infection in
      immunocompromised patients following allogeneic hematopoietic stem cell
      transplantation. The majority of studies have used steady-state leukapheresis for
      CMV-reactive product manufacture, a collection obtained prior to or months after
      G-CSF mobilization, but the procurement of this additional sample is often not
      available in the unrelated donor setting. If the cellular product for adoptive
      immunotherapy could be generated from the same G-CSF mobilized collection, the
      problems associated with the additional harvest could be overcome. Despite the
      tolerogenic effects associated with G-CSF mobilization, recent studies described
      that CMV-primed T cells generated from mobilized donors remain functional.
      METHODS: MHC-multimers are potent tools that allow the rapid production of
      antigen-specific CTLs. Therefore, in the present study we have assessed the
      feasibility and efficacy of CMV-specific CTL manufacture from G-CSF mobilized
      apheresis using MHC-multimers. RESULTS: CMV-specific CTLs can be efficiently
      isolated from G-CSF mobilized samples with Streptamers and are able to express
      activation markers and produce cytokines in response to antigenic stimulation.
      However, this anti-viral functionality is moderately reduced when compared to non
      mobilized products. CONCLUSIONS: The translation of Streptamer technology for the
      isolation of anti-viral CTLs from G-CSF mobilized PBMCs into clinical practice
      would widen the number of patients that could benefit from this therapeutic
      strategy, although our results need to be taken into consideration before the
      infusion of antigen-specific T cells obtained from G-CSF mobilized samples.

PMID- 25990025
TI  - The anatomical location of the corticoreticular pathway at the subcortical white
      matter in the human brain: A diffusion tensor imaging study.
AB  - We attempted to investigate the anatomical location of the corticoreticular
      pathway (CRP) in the subcortical white matter in the human. Thirty-three healthy
      volunteers were recruited. The locations of the CRP and corticospinal tract (CST)
      were defined as the location on axial slice of the centrum semiovale, corona
      radiata, and posterior limb of the internal capsule. The CRP was located close
      antero-medially to the CST in all three regions of subcortical white matter. 

PMID- 25990026
TI  - Amoeba-inspired nanoarchitectonic computing implemented using electrical Brownian
      ratchets.
AB  - In this study, we extracted the essential spatiotemporal dynamics that allow an
      amoeboid organism to solve a computationally demanding problem and adapt to its
      environment, thereby proposing a nature-inspired nanoarchitectonic computing
      system, which we implemented using a network of nanowire devices called
      'electrical Brownian ratchets (EBRs)'. By utilizing the fluctuations generated
      from thermal energy in nanowire devices, we used our system to solve the
      satisfiability problem, which is a highly complex combinatorial problem related
      to a wide variety of practical applications. We evaluated the dependency of the
      solution search speed on its exploration parameter, which characterizes the
      fluctuation intensity of EBRs, using a simulation model of our system called
      'AmoebaSAT-Brownian'. We found that AmoebaSAT-Brownian enhanced the solution
      searching speed dramatically when we imposed some constraints on the fluctuations
      in its time series and it outperformed a well-known stochastic local search
      method. These results suggest a new computing paradigm, which may allow high
      speed problem solving to be implemented by interacting nanoscale devices with low
      power consumption. 

PMID- 25990028
TI  - Necrotising (malignant) otitis externa in the UK: a growing problem. Review of
      five cases and analysis of national Hospital Episode Statistics trends.
AB  - BACKGROUND: Necrotising (malignant) otitis externa is a severe infection causing
      temporal bone osteomyelitis. Although rare, our experience (reported herein)
      shows local doubling of cases in 2013. Hospital Episodes Statistics data for
      England over 14 years also indicate increased incidence nationally. Specific
      learning points in management are also discussed. METHODS: A retrospective review
      was conducted of patients admitted in 2013 to Wexham Park Hospital, Slough, UK
      (catchment population, 450 000). In addition, the UK Government Hospital Episodes
      Statistics data were interrogated. RESULTS: There were five cases of necrotising
      (malignant) otitis externa in 2013, representing a local doubling on previous
      years. The mean age of patients was 82 years. All cultures grew Pseudomonas
      aeruginosa; no isolates were antibiotic resistant. All patients responded to
      systemic anti-pseudomonals on clinical, biochemical and radiological parameters.
      Hospital Episodes Statistics data showed a six-fold increase in the number of
      cases from 1999 (n = 67) to 2013 (n = 421). CONCLUSION: Our experience suggests
      increasing necrotising (malignant) otitis externa incidence, and retrospective
      analysis of Hospital Episodes Statistics data supports this observation.
      Necrotising (malignant) otitis externa poses challenges in management, as
      exemplified in our cases, requiring a high index of suspicion and early
      aggressive treatment to achieve cure.

PMID- 25990027
TI  - Motor practice effects and sensorimotor integration in adults who stutter:
      Evidence from visuomotor tracking performance.
AB  - PURPOSE: The purpose of this study was to utilize a visuomotor tracking task,
      with both the jaw and hand, to add to the literature regarding non-speech motor
      practice and sensorimotor integration (outside of auditory-motor integration
      domain) in adults who do (PWS) and do not (PWNS) stutter. METHOD: Participants
      were 15 PWS (14 males, mean age = 27.0) and 15 PWNS (14 males, mean age = 27.2).
      Participants tracked both predictable and unpredictable moving targets separately
      with their jaw and their dominant hand, and accuracy was assessed by calculating
      phase and amplitude difference between the participant and the target. Motor
      practice effect was examined by comparing group performance over consecutive
      tracking trials of predictable conditions as well as within the first trial of
      same conditions. RESULTS: Results showed that compared to PWNS, PWS were not
      significantly different in matching either the phase (timing) or the amplitude of
      the target in both jaw and hand tracking of predictable and unpredictable
      targets. Further, there were no significant between-group differences in motor
      practice effects for either jaw or hand tracking. Both groups showed improved
      tracking accuracy within and between the trials. CONCLUSION: Our findings
      revealed no statistically significant differences in non-speech motor practice
      effects and integration of sensorimotor feedback between PWS and PWNS, at least
      in the context of the visuomotor tracking tasks employed in the study. In
      general, both talker groups exhibited practice effects (i.e., increased accuracy
      over time) within and between tracking trials during both jaw and hand tracking.
      Implications for these results are discussed. EDUCATIONAL OBJECTIVES: The reader
      will be able to: (a) describe the importance of motor learning and sensory-motor
      integration for speech, (b) summarize past research on PWS's performance during
      speech and nonspeech motor tasks, and (c) describe the relation between different
      aspects of speech and non-speech motor control and stuttering.

PMID- 25990029
TI  - Using the taxon-specific genes for the taxonomic classification of bacterial
      genomes.
AB  - BACKGROUND: The correct taxonomic assignment of bacterial genomes is a primary
      and challenging task. With the availability of whole genome sequences, the gene
      content based approaches appear promising in inferring the bacterial taxonomy.
      The complete genome sequencing of a bacterial genome often reveals a substantial
      number of unique genes present only in that genome which can be used for its
      taxonomic classification. RESULTS: In this study, we have proposed a
      comprehensive method which uses the taxon-specific genes for the correct
      taxonomic assignment of existing and new bacterial genomes. The taxon-specific
      genes identified at each taxonomic rank have been successfully used for the
      taxonomic classification of 2,342 genomes present in the NCBI genomes, 36 newly
      sequenced genomes, and 17 genomes for which the complete taxonomy is not yet
      known. This approach has been implemented for the development of a tool
      'Microtaxi' which can be used for the taxonomic assignment of complete bacterial
      genomes. CONCLUSION: The taxon-specific gene based approach provides an alternate
      valuable methodology to carry out the taxonomic classification of newly sequenced
      or existing bacterial genomes.

PMID- 25990030
TI  - The stability domain of the selenide kesterite photovoltaic materials and NMR
      investigation of the Cu/Zn disorder in Cu2ZnSnSe4 (CZTSe).
AB  - Bulk compounds, prepared via the ceramic route, related to Cu2ZnSnSe4 (CZTSe), a
      material considered for use in photovoltaic devices, were investigated using NMR
      spectroscopy, electron-probe microanalyses and X-ray diffraction. These materials
      adopt the kesterite structure regardless of the Cu and Zn contents. It is also
      shown that the stability domain of the copper-poor quaternary phases is wider for
      selenide derivatives than for sulphides. Finally, the Cu/Zn disorder level in
      CZTSe is found to be higher when the samples are quenched, which is reminiscent
      of the behaviour of the parent sulphide compounds CZTS. 

PMID- 25990032
TI  - Cardiovascular pathology: A new journal for an old need.

PMID- 25990033
TI  - Cardiovascular pathology at the crossroads: The dilemma of cardiac pathologists.

PMID- 25990034
TI  - Parasitic diseases of the heart I: Acute and chronic Chagas' disease.

PMID- 25990035
TI  - The role of endothelial cell adhesion molecules in the development of
      atherosclerosis.
AB  - The vascular endothelium serves as a dynamic interface between circulating blood
      elements and the interstitial tissues. As such, it communicates to cells within
      the vessel wall as well as to the surrounding tissue, sensing its environment and
      responding accordingly. The vasculature must maintain a delicate balance when
      initiating a functional response by producing both proinflammatory and
      antiinflammatory mediators, vasoconstrictors and vasodilators, growth stimulators
      and inhibitors, and prothrombogenic and antithrombogenic factors. Any response to
      injurious agents could lead to pathology. Confounding this complex interplay is
      the fact that the very response to injury that may have developed to undo the
      damage may itself be even more deleterious. One response to injury by the
      endothelium is the new or increased expression of surface receptors for immune
      elements. In atherosclerosis, the adhesion of monocytes (and T cells) to the
      endothelium is a key event triggered by some form of insult. Subsequent events
      include monocytic infiltration of the vessel wall, alterations in lipid
      metabolism, and the activation of these cells into foam cells. The presence of
      large numbers of foam cells in the intima may produce a high concentration of
      cytokines and growth factors within a localized area, extracellular matrix
      perturbations, smooth muscle cell proliferation, and ultimately platelet
      aggregation at the site of stenosis. Endothelial cells themselves will not only
      elaborate factors after the initial injury to the vessel wall but also in
      response to the factors produced by foam cells within the plaque. These
      endothelial cell factors include MCP-1, a chemoattractant for monocytes
      (179,180), IL-1 (63,64), IL-6 (interleukin-6) (65-67), IL-8 (interleukin 8)
      (181), and PDGF, a potent smooth muscle mitogen (4,72) (Fig. 3). Endothelial
      cells will propagate an inflammatory response long after the initial insult to
      the arterial vessel. A chronic cycle of endothelial cell activation and leukocyte
      infiltration is constitutively activated. Thus, all of the cellular elements of
      the vessel wall, as well as the atherosclerotic plaque itself, elaborate
      cytokines and growth factors that amplify and propagate the pathological process.

PMID- 25990036
TI  - Pathological considerations in replacement cardiac valves.

PMID- 25990037
TI  - AIDS and the heart: Review and consideration of pathogenetic mechanisms.
AB  - Many of the diverse pathologic manifestations of heart disease in acquired immune
      deficiency syndrome (AIDS) may relate ultimately to immune dysfunction and
      opportunistic infection, but other important changes occur, including myocarditis
      and cardiomyopathy, which may have less clear pathogeneses. We review findings
      from our AIDS autopsy series and comment on the findings and thoughts of others
      studying pathologic changes in the heart in AIDS. 

PMID- 25990038
TI  - Atherosclerotic abdominal aortic aneurysms: Comparative data of different types
      based on the degree of inflammatory reaction.
AB  - Two-hundred two patients who consecutively underwent histological examination of
      the aneurysm wall with the full thickness at the time of repair procedure of
      infrarenal true abdominal aortic aneurysm were retrieved from the files of the
      Department of Pathology at the National Cardiovascular Center in the 13-year
      period from September 1977 to August 1990. Inflammatory aneurysms were present in
      15 patients (7.4%);14 men, 1 woman. The other 187 patients with ordinary
      atherosclerotic aneurysms were classified into four groups according to the
      thickness of adventitia and periadventitia, and clinical and pathological
      variables were compared between these groups and patients with inflammatory
      aneurysms. Patients with inflammatory aneurysms were significantly more likely to
      be younger and demonstrate weight loss, ureteric obstruction, absence of
      abdominal bruit, more accelerated erythrocyte sedimentation rate, and more
      thickening of adventitial and periadventitial tissue. The microscopic features of
      ordinary atherosclerotic aneurysms that had remarkable thickening of adventitia
      and periadventitia showed no sharp distinction from those of inflammatory
      aneurysms. Our study suggests that atherosclerosis plays a major role in the
      aneurysmal dilatation of the aorta and in the periaortic inflammatory process,
      and that inflammatory aneurysms are located at one end of the spectrum of
      atherosclerotic abdominal aortic aneurysms. 

PMID- 25990039
TI  - Inflammatory aneurysm of the aorta or chronic periaortitis: A nosologic quandry.

PMID- 25990040
TI  - [New technologies in the prosthetic management after amputations].
AB  - BACKGROUND: In Germany around 70,000 amputations are carried out on extremities
      each year. Modern prosthetic functional components have become more and more
      sophisticated and must be understood and applied by their users to be of
      beneficial use in everyday life. The prosthetic socket is the most important
      component of modern extremity prosthetics. OBJECTIVES: Which demands have to be
      met by a modern prosthetic socket so that innovative function-improving
      components in prosthetics can be successfully applied? MATERIALS AND METHODS:
      Complex prosthetic technologies are rarely compatible with a lower overall weight
      of the prosthesis. The increase in functionality also produces differentiated
      force effects on the human body. Modern socket technologies, therefore, have to
      compensate for the increased strain and counteract the increasing dynamics
      between the stump and the prosthesis. This can be achieved through the
      application of adhesive socket materials and through new adhesive mechanisms.
      Form variants can also improve the connection between stump and prosthetic
      socket. RESULTS: The improvements in prosthetic socket technology presented here
      have a lasting positive effect on the daily routine of many amputees. Not only do
      they improve the control and application of modern prosthetic components, but
      also clearly enhance the wearing comfort. CONCLUSION: The prosthetic socket is
      crucial for the success of exoskeletal prosthetic management. The better we
      succeed in making the human body and the prosthetic socket an entity, the more
      usefully and comfortably innovative prosthetic methods can be applied.

PMID- 25990041
TI  - Complete mitochondrial genome of a sunbird, Aethopyga gouldiae (Aves:
      Passeriformes), the first representative of Nectariniidae.
AB  - The first complete mitochondrial genome of a sunbird was determined for Gould's
      sunbird Aethopyga gouldiae. The identity of the sample was verified by conducting
      nucleotide blast for each mitochondrial ribosomal RNA and protein-coding gene,
      and by estimating its phylogenetic position using five genes (12S, ND2, ATP6,
      ND3, CYTb) and 52 passerines (including 17 sunbirds and allies). The mitogenomic
      length of A. gouldiae was 16,893 bp, including 13 protein-coding genes, 22
      transfer RNA genes, 2 ribosomal RNA genes and 1 control region. The nucleotide
      composition of the genome shows a bias toward A + T. Since the sunbirds and
      allies form a large bird group that feeds on nectar, along with the hummingbirds
      and honeyeaters, the mitogenome of A. gouldiae could contribute to understand the
      evolution of feeding behavior in birds and the phylogenetic position of the
      sunbirds.

PMID- 25990043
TI  - Survival and Stationary Distribution Analysis of a Stochastic Competitive Model
      of Three Species in a Polluted Environment.
AB  - In this paper, we develop and study a stochastic model for the competition of
      three species with a generalized dose-response function in a polluted
      environment. We first carry out the survival analysis and obtain sufficient
      conditions for the extinction, non-persistence, weak persistence in the mean,
      strong persistence in the mean and stochastic permanence. The threshold between
      weak persistence in the mean and extinction is established for each species.
      Then, using Hasminskii's methods and a Lyapunov function, we derive sufficient
      conditions for the existence of stationary distribution for each population.
      Numerical simulations are carried out to support our theoretical results, and
      some biological significance is presented. 

PMID- 25990042
TI  - Tumor-Targeting Co-Delivery of Drug and Gene from Temperature-Triggered Micelles.
AB  - Co-delivery strategy using multifunctional nanocarriers is an attractive option
      for the synergistic and enhanced effects in cancer treatment, but one system
      integrating multiple functions for controlled release at the target is still
      challenging. Herein, this study shows the synthesis and characterization of our
      stimulus-responsive co-delivery system for the controlled release into tumors,
      which is composed of polyethylenimine (PEI)-linked Pluronic F127 (PF127) and
      folic acid (FA), called PF127-PEI-FA. PF127-PEI-FA system facilitated drug
      loading and gene complex formation, and showed controlled release behaviors in
      response to hitting temperature to hyperthermia. PF127-PEI-FA system was
      demonstrated to be biocompatible and showed receptor-mediated gene delivery. The
      results of our multifunctional nanocarrier system that enabled co-delivery
      suggest a promising potential for controlled drug release at targeted areas.
      However, further in-depth studies on the use of therapeutic drugs and genes in
      multiple cell types and the animal response are required. 

PMID- 25990044
TI  - Role of Toll like receptor 4 signaling pathway in the secondary damage induced by
      experimental spinal cord injury.
AB  - Toll-like receptors (TLRs) are signaling receptors in the innate immune system
      that is specific immunologic response to systemic bacterial infection and injury.
      TLRs contribute to the initial induction of neuroinflammation in the CNS. In
      spinal cord injury (SCI) intricate immune cell interactions are triggered,
      typically consisting of a staggered multiphasic immune cell response, which can
      become deregulated. The present study aims to evaluate the role of TLR4 signaling
      pathway in the development of secondary damage in a mouse model of SCI using TLR4
      deficient (TLR4-KO) mice such as C57BL/10ScNJ and C3H/HeJ mice. We evaluated
      behavioral changes, histological, immunohistochemistry and molecular assessment
      in TLR4-KO after SCI. SCI was performed on TLR4-KO and wild-type (WT) mice by the
      application of vascular clips (force of 24g) to the dura via a four-level T5-T8
      laminectomy. Mice were sacrificed at 24h after SCI to evaluate the various
      parameters. SCI TLR4 KO mice developed severer hind limb motor dysfunction and
      neuronal death by histological evaluation, myeloid differentiation primary
      response 88 (Myd88) expression as well as an increase in nuclear factor NF-kappaB
      activity, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels,
      glial fibrillary acidic protein (GFAP), microglia marker (CD11beta), inducible
      nitric oxide synthases (iNOS), poly-ADP-ribose polymerase (PARP) and
      nitrotyrosine expression compared to WT mice. Moreover, the absence of TLR4 also
      caused a decrease in phosphorylated interferon regulatory transcription factor (p
      IRF3) and interferon (IFN-beta) release. In addition, SCI TLR4 KO mice showed in
      spinal cord tissues a more pronounced up-regulation of Bax and a down-regulation
      of Bcl-2 compared to SCI WT mice. Finally, we clearly demonstrated that TLR4 is
      important for coordinating post-injury sequel and in regulating inflammation
      after SCI.

PMID- 25990045
TI  - A mixed-methods exploration of implementation of a comprehensive school healthy
      eating model one year after scale-up.
AB  - OBJECTIVE: To study the implementation of a school-based healthy eating (HE)
      model one year after scale-up in British Columbia (BC). Specifically, to examine
      implementation of Action Schools! BC (AS! BC) and its influence on implementation
      of classroom HE activities, and to explore factors associated with
      implementation. DESIGN: Diffusion of Innovations, Social Cognitive and
      Organizational Change theories guided our approach. We used a mixed-methods
      research design including focus group interviews (seven schools, sixty-two
      implementers) and a cross-sectional multistage survey to principals (n 36, 92 %
      response rate) and teachers of grades 4 to 7 (n 168, 70 % response rate). Self
      reported implementation of classroom HE activities and reported use of specific
      AS! BC HE activities were primary implementation measures. Thematic analysis of
      focus group data and multilevel mixed-effect logistic regression analyses of
      survey data were conducted. SETTING: Elementary schools across BC, Canada.
      SUBJECTS: Thirty-nine school districts, thirty-six principals, 168 grade 4 to 7
      teachers. RESULTS: Forty-two per cent of teachers in registered schools were
      implementing AS! BC HE in their classrooms. Users were 6.25 times more likely to
      have delivered a HE lesson in the past week. Implementation facilitators were
      school champions, technical support and access to resources; barriers were lack
      of time, loss of leadership or momentum. Implementation predictors were teacher
      training, self-efficacy, experience with the physical activity component of AS!
      BC, supportive school climate and parental post-secondary education. CONCLUSIONS:
      Our findings reinforce that continued teacher training and support are important
      public health investments that contribute to successful implementation of school
      based HE models after scale-up.

PMID- 25990046
TI  - The impact of home health length of stay and number of skilled nursing visits on
      hospitalization among Medicare-reimbursed skilled home health beneficiaries.
AB  - The implementation of the Home Health Prospective Payment System in 2000 led to a
      dramatic reduction in home health length of stay and number of skilled nursing
      visits among Medicare beneficiaries. While policy leaders have focused on the
      rising costs of home health care, its potential underutilization, and the
      relationship between service use and patient outcomes including hospitalization
      rates have not been rigorously examined. A secondary analysis of five Medicare
      owned assessment and claims data sets for the year 2009 was conducted among two
      independently randomly selected samples of Medicare-reimbursed home health
      recipients (each n = 31,485) to examine the relationship between home health
      length of stay or number of skilled nursing visits and hospitalization rates
      within 90 days of discharge from home health. Patients who had a home health
      length of stay of at least 22 days or received at least four skilled nursing
      visits had significantly lower odds of hospitalization than patients with shorter
      home health stays and fewer skilled nursing visits. Additional study is needed to
      clarify the best way to structure home health services and determine readiness
      for discharge to reduce hospitalization among this chronically ill population. In
      the mean time, the findings of this study suggest that home health providers
      should consider the benefits of at least four SNV and/or a home health LOS of 22
      days or longer.

PMID- 25990047
TI  - Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees
      with Gitelman syndrome and review of literature.
AB  - OBJECTIVE: Gitelman syndrome (GS) is one of the most common causes of inherited
      hypokalaemia. As it was caused by mutations in the SLC12A3 gene, GS is a highly
      heterogeneous disease. Here, we aimed to investigate the clinical and genetic
      characteristics of two Chinese pedigrees and summarize the advance in GS
      genetics, diagnosis and management. SUBJECTS AND METHODS: Two three-generation
      families with GS were identified and screened for mutations in the SLC12A3 gene.
      Genotype-phenotype correlations were analysed. RESULTS: The two probands (A and
      B) were characterized by hypokalaemia, hypomagnesaemia and hypocalciuria without
      hypertension. Complete DNA sequencing of the SLC12A3 gene revealed two novel
      compound heterozygous mutations (c.179C>T and c.234delG; c.486-490delTACGGinsA
      and c.1925G>A), which are predicted to drastically affect normal protein
      structure. The female members of the pedigrees showed mild-to-no phenotype,
      although they carried the same mutations as the probands. Moreover, proband B
      presented with more severe symptoms than did proband A, which might be related to
      a lower serum magnesium level. During the 1-year follow-up, both probands showed
      satisfactory symptom improvement following the use of potassium and magnesium
      supplements. CONCLUSION: Our findings strongly suggested that the two novel
      mutations in the SLC12A3 gene are the causative agents of GS, which may provide
      further insights into the function of this gene and help clinicians better
      understand this disorder.

PMID- 25990048
TI  - Vital Signs Are Not Associated with Self-Reported Acute Pain Intensity in the
      Emergency Department.
AB  - OBJECTIVES: This study aimed to ascertain the association between self-reported
      pain intensity and vital signs in both emergency department (ED) patients and a
      subgroup of patients with diagnosed conditions known to produce significant pain.
      METHODS: We performed a retrospective analysis of real-time, archived data from
      an electronic medical record system at an urban teaching hospital and regional
      community hospital. We included consecutive ED patients >=16 years old who had a
      self-reported pain intensity >=1 as measured during triage, from March 2005 to
      December 2012. The primary outcome was vital signs for self-reported pain
      intensity levels (mild, moderate, severe) on an 11-point verbal numerical scale.
      Changes in pain intensity levels were also compared to variations in vital signs.
      Both analyses were repeated on a subgroup of patients with diagnosed conditions
      recognized to produce significant pain: fracture, dislocation, or renal colic.
      RESULTS: We included 153,567 patients (mean age of 48.4+/-19.3 years; 55.5%
      women) triaged with pain (median intensity of 7/10+/-3). Of these, 8.9% of
      patients had diagnosed conditions recognized to produce significant pain. From
      the total sample, the difference between mild and severe pain categories was 2.7
      beats/minutes (95% CI: 2.4-3.0) for heart rate and 0.13 mm Hg (95% CI: -0.26
      0.52) for systolic blood pressure. These differences generated small effect sizes
      and were not clinically significant. Results were similar for patients who
      experienced changes in pain categories and for those conditions recognized to
      produce significant pain. CONCLUSION: Health care professionals cannot use vital
      signs to estimate or substantiate self-reported pain intensity levels or changes
      over time.

PMID- 25990049
TI  - Basophil activation by mosquito extracts in patients with hypersensitivity to
      mosquito bites.
AB  - Hypersensitivity to mosquito bites (HMB) is a cutaneous disorder belonging to the
      group of Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell
      lymphoproliferative diseases, and is primarily mediated by EBV-infected NK cells.
      It is characterized by intense local skin reactions accompanied by general
      symptoms after mosquito bites, and infiltration of EBV-infected NK cells into the
      bite sites. However, the mechanisms underlying these reactions have not been
      fully examined. We recently described the activation of circulating basophils by
      mosquito extracts in vitro in a patient with HMB. To further investigate this
      finding, we studied four additional patients with HMB. All patients showed
      typical clinical features of HMB after mosquito bites and they had NK
      lymphocytosis and high peripheral blood EBV DNA loads. We found evidence of EBV
      infection in NK cells through in situ hybridization that detected EBV-encoded
      small RNA-1, and flow cytometry showed HLA-DR expression on almost all NK cells.
      Basophil activation tests with the extracts of epidemic mosquitoes Culex pipiens
      pallens and Aedes albopictus showed positive responses to one or both extracts in
      all samples from patients with HMB, suggesting the presence of mosquito antigen
      specific IgE and its binding to basophils. In particular, the extract of Aedes
      albopictus was able to activate basophils in all available patient samples. These
      results indicate that basophils and/or mast cells activated by mosquito bites may
      be involved in initiation and development of severe skin reactions to mosquito
      bites in HMB. 

PMID- 25990050
TI  - Treatment of diabetes with encapsulated pig islets: an update on current
      developments.
AB  - The potential use of allogeneic islet transplantation in curing type 1 diabetes
      mellitus has been adequately demonstrated, but its large-scale application is
      limited by the short supply of donor islets and the need for sustained and heavy
      immunosuppressive therapy. Encapsulation of pig islets was therefore suggested
      with a view to providing a possible alternative source of islet grafts and
      avoiding chronic immunosuppression and associated adverse or toxic effects.
      Nevertheless, several vital elements should be taken into account before this
      therapy becomes a clinical reality, including cell sources, encapsulation
      approaches, and implantation sites. This paper provides a comprehensive review of
      xenotransplantation of encapsulated pig islets for the treatment of type 1
      diabetes mellitus, including current research findings and suggestions for future
      studies. 

PMID- 25990052
TI  - Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients
      with diabetes mellitus type 2.
AB  - OBJECTIVE: Uncontrolled diabetes has become a major cause of mortality and
      morbidity by reason of vascular angiopathy. The aim of this study was to evaluate
      the concentrations of soluble forms of vascular adhesion molecule-1 (sVCAM-1),
      intercellular adhesion molecule-1 (sICAM-1), E-selectin, and thrombomodulin in
      patients with well-controlled and uncontrolled diabetes type 2. METHODS: The
      study was conducted on 62 patients with diabetes. Group I consisted of 35
      patients with well-controlled diabetes. The second group included 27 patients
      with uncontrolled diabetes with micro-albuminuria. A control group was made up of
      25 healthy volunteers. The concentrations of sVCAM-1, sICAM-1, sE-selectin, and
      soluble thrombomodulin were assayed in plasma. Serum concentration of creatinine
      was measured and the plasma concentrations of fasting glucose and glycated
      hemoglobin (HbA1c) determined. RESULTS: Lower concentrations of ICAM-1 were found
      in the group of uncontrolled diabetes patients compared with those with well
      controlled disease. In patients with uncontrolled diabetes, VCAM-1 levels were
      significantly higher compared with the group with well-controlled diabetes. In
      patients with uncontrolled diabetes a positive correlation was obtained between
      glomerular filtration rate and sE-selectin and a negative correlation between the
      levels of creatinine and ICAM-1, although there was a positive correlation
      between (HbA1c) and ICAM-1. CONCLUSIONS: The study confirmed the participation of
      the inflammatory process associated with impaired vascular endothelial function
      in the pathogenesis of type 2 diabetes. The opposite effect of uncontrolled
      hyperglycemia on adhesion molecules suggests different functions of VCAM-1 and
      ICAM-1 in complications of diabetes.

PMID- 25990051
TI  - Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in
      streptozotocin-induced diabetic rats.
AB  - We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat
      model induced with high-fat diet and intraperitoneal injection of streptozotocin.
      Ginsenoside Rg1 was injected intraperitoneally for 12 weeks. Myocardial injury
      indices and oxidative stress markers were determined. Changes in cardiac
      ultrastructure were evaluated with transmission electron microscopy. Myocardial
      apoptosis was assessed via terminal deoxynucleotidyl transferase (TDT)-mediated
      DNA nick-end labeling (TUNEL) and immunohistochemistry. Ginsenoside Rg1 was
      associated with a significant dose-dependent reduction in serum levels of
      creatinine kinase MB and cardiac troponin I, and lessened ultrastructural
      disorders in diabetic myocardium, relative to the untreated diabetic model rats.
      Also, compared with the untreated diabetic rats, significant reductions in serum
      and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1
      treated groups, and increased levels of the antioxidants (superoxide dismutase,
      catalase, and glutathione peroxidase) were detected. TUNEL staining indicated
      reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be
      associated with reduced levels of caspase-3 (CASP3) and increased levels of B
      cell lymphoma-extra-large (Bcl-xL) in the diabetic myocardium. Ginsenoside Rg1
      treatment of diabetic rats was associated with reduced oxidative stress and
      attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of
      potential preventative and therapeutic value for cardiovascular injury in
      diabetic patients. 

PMID- 25990053
TI  - Mineral metabolism disturbances are associated with the presence and severity of
      calcific aortic valve disease.
AB  - OBJECTIVE: We investigated whether disturbance of calcium and phosphate
      metabolism is associated with the presence and severity of calcific aortic valve
      disease (CAVD) in patients with normal or mildly impaired renal function.
      METHODS: We measured serum levels of calcium, phosphate, alkaline phosphatase
      (AKP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), and
      biomarkers of bone turnover in 260 consecutive patients with normal or mildly
      impaired renal function and aortic valve sclerosis (AVSc) (n=164) or stenosis
      (AVS) (n=96) and in 164 age- and gender-matched controls. Logistic regression
      models were used to determine the association of mineral metabolism parameters
      with the presence and severity of CAVD. RESULTS: Stepwise increases were observed
      in serum levels of calcium, phosphate, AKP, and iPTH from the control group to
      patients with AVS, and with reverse changes for 25-OHD levels (all P<0.001).
      Similarly, osteocalcin, procollagen I N-terminal peptide, and beta-isomerized
      type I collagen C-telopeptide breakdown products were significantly increased
      stepwise from the control group to patients with AVS (all P<0.001). In patients
      with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were
      negatively, related to trans-aortic peak flow velocity and mean pressure
      gradient. After adjusting for relevant confounding variables, increased serum
      levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD
      were independently associated with the presence and severity of CAVD.
      CONCLUSIONS: This study suggests an association between mineral metabolism
      disturbance and the presence and severity of CAVD in patients with normal or
      mildly impaired renal function. Abnormal bone turnover may be a potential
      mechanism.

PMID- 25990054
TI  - Meta-analysis of C242T polymorphism in CYBA genes: risk of acute coronary
      syndrome is lower in Asians but not in Caucasians.
AB  - BACKGROUND: A lot of studies have demonstrated that C242T polymorphism in CYBA
      genes may play an important role in the pathological process of acute coronary
      syndrome (ACS). However, the results are not consistent. To further evaluate this
      debate, we performed a meta-analysis to determine the relationship between C242T
      polymorphism and ACS. METHODS AND RESULTS: We screened PubMed/MEDLINE, EBSCIO,
      and EMBASE research reports until Mar. 2014 and extracted data from 10 studies
      involving 6102 ACS patients and 8669 controls. Subgroup analysis by ethnicity
      documented a significant decreased risk of ACS for C242T polymorphism in the
      Asian population under allelic comparison (odd ratio (OR) 0.73; 95% confidence
      intervals (CI) 0.64-0.83), dominant model (OR 0.71; 95% CI 0.62-0.82), and
      homozygote comparison (OR 0.57; 95% CI 0.35-0.92). However, in the overall
      population and especially with Caucasians, no significant association was
      uncovered. Further meta-regression analysis revealed that the heterogeneity among
      studies was largely attributed to ethnicity. No publication bias was detected
      through a funnel plot and an Egger's linear regression test. CONCLUSIONS: Taken
      together, our results suggest that the C242T polymorphism might be a protective
      factor against developing ACS in the Asian population. Further researches will be
      needed to identify the confounding factors which modified the protective effect
      of T allele among Caucasians.

PMID- 25990056
TI  - Treatment and prognosis of cervical cancer associated with pregnancy: analysis of
      20 cases from a Chinese tumor institution.
AB  - This study was designed to investigate the therapeutic approaches and prognosis
      for cervical cancer associated with pregnancy. Clinical information, therapeutic
      strategies, and follow-up results of 20 patients with cervical cancer associated
      with pregnancy from Jan. 2000 to June 2009 in the Zhejiang Cancer Hospital were
      retrospectively analyzed. The International Federation of Gynecology and
      Obstetrics (FIGO) stages were: in situ (n=1), stage IA1 (n=1), stage IB1 (n=5),
      stage IB2 (n=1), stage IIA (n=8), stage IIB (n=3), and stage IIIB (n=1). Eight
      patients were in the first trimester of pregnancy, four in the second, two in the
      third, and six at postpartum when diagnosed. The therapeutic strategies were
      either single or combined modalities, including surgery, radiotherapy, and
      chemotherapy. Fourteen patients survived, five patients died (four of remote
      metastasis and one of uremia), and one patient was lost to follow-up. One newborn
      from a patient at stage IIA carcinoma in the third trimester with postponed
      therapy six weeks after diagnosis survived. Retarded fetal growth was observed in
      one patient receiving neoadjuvant chemotherapy and cesarean section. Out of the
      six postpartum patients, three underwent cesarean section and survived, whereas
      only one out of the three who underwent vaginal delivery survived. The remaining
      two died of remote metastasis. Therefore, personalized treatment is necessary for
      cervical cancer associated with pregnancy. Cervical cancer patients in the third
      trimester of pregnancy can continue the pregnancy for a short period of time.
      There may be potential risk for the fetus by chemotherapy during pregnancy.
      Cesarean section is the preferred mode of delivery for pregnant cervical cancer
      patients. 

PMID- 25990055
TI  - Pitavastatin calcium improves endothelial function and delays the progress of
      atherosclerosis in patients with hypercholesterolemia.
AB  - BACKGROUND: Statins have proven efficacy in inhibiting the onset and progress of
      atherosclerosis. The effectiveness of pitavastatin in reversing carotid
      atherosclerosis associated with hypercholesterolemia (HC) is unknown. OBJECTIVES:
      To explore the simultaneous effects of pitavastatin calcium on brachial arterial
      flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and
      arterial stiffness (beta), three surrogate markers of atherosclerosis were
      studied in HC patients. METHODS: A randomized, double-blind trial was performed
      with 40 HC subjects who fulfilled the inclusion/exclusion criteria. Patients were
      given pitavastatin calcium 1 mg/d (Group 1) or 2 mg/d (Group 2) for 8 weeks.
      There were 20 patients in each group, and 30 gender- and age-matched healthy
      subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and
      arterial stiffness indicated by beta were measured at baseline and at 8 weeks
      after starting pitavastatin calcium therapy using ultrasound techniques.
      Biochemical tests were also made on all subjects. RESULTS: At baseline, higher
      total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduced
      FMD, and increased beta and IMT were observed in HC patients (P<0.001 for all)
      compared with controls. After 8 weeks, TC was decreased by 20.59%/27.56% and LDL
      C 30.92%/35.64%, respectively, in comparison to baseline groups; the HC groups
      had reduced beta and improved endothelial function over the 8-week follow-up
      (P<0.05-0.001); nonetheless, no significant alterations of IMT were found
      (P>0.05). Significant negative interactions between TC/LDL and FMD (P<0.05
      0.001), positive interactions between TC and IMT (P=0.003) and between TC/LDL and
      beta (P<0.001-0.000) were found. CONCLUSIONS: Treatment with pitavastatin calcium
      exerted favorable effects on endothelial function and arterial stiffness. It also
      improved carotid atherosclerosis in patients with HC.

PMID- 25990057
TI  - Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood
      salvage but preserves the function of erythrocytes.
AB  - The safe use of intraoperative blood salvage (IBS) in cancer surgery remains
      controversial. Here, we investigated the killing effect of cisplatin combined
      with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from
      IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and
      pretreated with cisplatin (50, 100, and 200 MUg/ml) alone at 37  degrees C for 60
      min and cisplatin (25, 50, 100, and 200 MUg/ml) combined with hyperthermia at 42 
      degrees C for 60 min. After pretreatment, the cell viability, colony formation
      and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3
      diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic
      fragility, membrane phosphatidylserine externalization, and blood gas variables
      in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200
      MUg/ml) combined with hyperthermia (42  degrees C) for 60 min significantly
      decreased HepG2 cell viability, and completely inhibited colony formation and DNA
      metabolism when the HepG2 cell concentration was 5*10(4) ml(-1) in the
      erythrocyte (P<0.01). Erythrocytic Na(+)-K(+)-ATPase activity, 2,3-DPG level,
      phosphatidylserine externalization, and extra-erythrocytic free Hb were
      significantly altered by hyperthermia plus high concentrations of cisplatin (100
      and 200 MUg/ml) (P<0.05), but not by hyperthermia plus 50 MUg/ml cisplatin
      (P>0.05). In conclusion, pretreatment with cisplatin (50 MUg/ml) combined with
      hyperthermia (42  degrees C) for 60 min effectively eliminated HepG2 cells from
      IBS but did not significantly affect erythrocytes in vitro. 

PMID- 25990059
TI  - Erratum to: Synthetic promoters consisting of defined cis-acting elements link
      multiple signaling pathways to probenazole-inducible system.

PMID- 25990058
TI  - CRP, but not TNF-alpha or IL-6, decreases after weight loss in patients with
      morbid obesity exposed to intensive weight reduction and balneological treatment.
AB  - OBJECTIVE: The aim of this study was to evaluate the concentrations of C-reactive
      protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      the degree of homeostasis model assessment-insulin resistance (HOMA-IR) in
      patients with morbid obesity exposed to a three-week low-calorie diet and
      balneotherapy. METHODS: The study included 33 patients (25 females and 8 males;
      mean age 46 years) with body mass index (BMI) values of >40 kg/m(2). Evaluations
      of CRP, IL-6, TNF-alpha, lipid profile, HOMA-IR, and fasting glucose were carried
      out before (baseline data) and three weeks after the treatment. The control group
      consisted of 20 healthy volunteers (15 females and 5 males) with a mean age of 39
      years and BMI values of <=24.9 kg/m(2). RESULTS: In the blood of patients with
      morbid obesity we found significantly elevated levels of CRP, TNF-alpha,
      triglycerides, HOMA-IR and fasting glucose, but a decreased level of high density
      lipoprotein (HDL)-cholesterol, compared with the healthy individuals. The
      treatment resulted in about a 9.4% reduction in body weight from 122.5 to 111.0
      kg and a significant decrease in the concentration of CRP, but no change in TNF
      alpha or IL-6. HOMA-IR was significantly reduced. CONCLUSIONS: The decrease in
      CRP level without changes in TNF-alpha or IL-6 concentrations after the low
      calorie diet and balneological treatment, suggests that an essential amount of
      adipose tissue must be removed before proper adipocyte function is restored. The
      decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is
      beneficial in obese patients.

PMID- 25990060
TI  - Head louse control by suffocation due to blocking their oxygen uptake.
AB  - The present study shows that head lice (Pediculus humanus capitis) are killed by
      suffocation when submersed into the anti-louse shampoo Licener(r), which contains
      a mild shampoo component and an extract of neem seeds after their oil components
      had been pressed off. It is shown that the inner tracheal system becomes
      completely filled by the very fluid product. Within 3-10 min, oxygen uptake is
      prohibited and death of all thus treated lice stages occurred.

PMID- 25990061
TI  - Molecular identification, immunolocalization, and characterization of Clonorchis
      sinensis triosephosphate isomerase.
AB  - Clonorchis sinensis triosephosphate isomerase (CsTIM) is a key regulatory enzyme
      of glycolysis and gluconeogenesis, which catalyzes the interconversion of
      glyceraldehyde 3-phosphate to dihydroxyacetone phosphate. In this study, the
      biochemical characterizations of CsTIM have been examined. A full-length
      complementary DNA (cDNA; Cs105350) sequence encoding CsTIM was obtained from our
      C. sinensis cDNA library. The open reading frame of CsTIM contains 759 bp which
      encodes 252 amino acids. The amino acid sequence of CsTIM shares 60-65% identity
      with other species. Western blot analysis displayed that recombinant CsTIM
      (rCsTIM) can be probed by anti-rCsTIM rat serum and anti-C. sinensis
      excretory/secretory products (anti-CsESPs) rat serum. Quantitative reverse
      transcription (RT)-PCR and western blotting analysis revealed that CsTIM
      messenger RNA (mRNA) and protein were differentially expressed in development
      cycle stages of the parasite, including adult worm, metacercaria, excysted
      metacercaria, and egg. In addition, immunolocalization assay showed that CsTIM
      was located in the seminal vesicle, eggs, and testicle. Moreover, rCsTIM
      exhibited active enzyme activity in catalytic reactions. The Michaelis constant
      (K m) of rCsTIM was 0.33 mM, when using glyceraldehyde 3-phosphate as the
      substrate. The optimal temperature and pH of CsTIM were 37  degrees C and 7.5
      9.5, respectively. Collectively, these results suggest that CsTIM is an important
      protein involved in glycometabolism, and CsTIM possibly take part in many
      biological functions in the growth and development of C. sinensis.

PMID- 25990062
TI  - Onchocerciasis caused by Onchocerca lupi: an emerging zoonotic infection.
      Systematic review.
AB  - Globalization has increased circulation of people, their food, livestock and pets
      in the world, and changes in the environment, climate and human behaviour have
      led to the rapid expansion of emerging infections throughout the world. One of
      the reasons of a new pathogen affecting humans is the passage from an animal to a
      human being. Onchocerca (O.) lupi, a filarial worm first described in a wolf in
      1967, is an emerging pathogen which has been incriminated as the etiological
      agent for 205 canine, 2 feline and 18 human infections in Europe, Tunisia,
      Turkey, Iran and the USA. Most frequent findings in animals and humans are
      monolateral or asymmetrical variably painful subconjunctival swellings and
      nodules containing immature or mature worms affecting the eye and/or adjacent
      tissues accompanied by conjunctival hyperemia. Occasionally, subcutaneous nodules
      and masses affecting the spinal cord have been observed in humans. Diagnosis of
      O. lupi is achieved by microscopy of excised adult female worms which exhibit a
      particular cuticular structure and molecular analysis. Treatment consists in worm
      removal accompanied by antihelminthic, antibiotic and anti-inflammatory therapy. 

PMID- 25990064
TI  - Transmyocardial laser revascularization: histopathological findings.
AB  - Transmyocardial laser revascularization (TMLR) is a new surgical technique
      clinically tested in patients with advanced severe coronary arteriosclerosis when
      classic routine treatment by medicaments, percutaneous transluminal coronary
      angioplasty (PTCA), or aorto-coronary bypass surgery does not improve symptoms of
      ischemic heart disease. During the procedure high-energy CO 2 laser performs 35
      40 transmyocardial channels via left-sided thoracotomy. Channels are drilled from
      the epicardial side of the heart through the myocardium into the left ventricle
      cavity. Impulses are synchronized with EKG (diastole), the channel diameter is
      about 1 mm. Transmural laser penetration is confirmed by intraoperative
      transesophageal echocardiography (TEE). This technique is based on a theory that
      channels allow blood supply from left ventricle directly into the intramyocardial
      vessels (possibly capillaries) and so improve oxygenation of ischemic myocardium.
      Presented are gross and microscopic findings in a 75-year-old woman who suffered
      from classic class IV angina with shortness of breath. She had a history of an
      inferior myocardial infarct, ventricular tachyarrhythmia, aorto-coronary bypass,
      and mitral valvuloplasty. Her ejection fraction by echocardiography was 25%.
      Angiographically, she had multiple occlusions of native coronary arteries and
      diffuse distal stenosis in the graft of the left internal mammary artery (LIMA)
      to the left anterior descending coronary artery (LAD). Thirty six of forty laser
      pulses were confirmed by TEE as transmural. The patient died suddenly of
      ventricular fibrillation 5 days after TMLR surgery. The autopsy was performed 6
      hours after death. After cross-sectioning of the heart all the laser-bored
      channels were found partially or completely filled by fibrin and cell infiltrate
      composed mainly of polymorphonuclear leukocytes. Patent channels were found
      within myocardial scars, channels performed through viable myocardium appeared to
      be partially collapsed and occluded. 

PMID- 25990063
TI  - Is impaired response inhibition independent of symptom dimensions in obsessive
      compulsive disorder? Evidence from ERPs.
AB  - Impaired response inhibition has been consistently reported in patients diagnosed
      with obsessive-compulsive disorder (OCD). This clinically heterogeneous disorder
      is characterized by several symptom dimensions that may have distinct, but
      partially overlapping, neural correlates. The present study examined whether
      alterations in response inhibition may be related to symptom severity and symptom
      dimensions. Event-related potentials (ERPs) were recorded in a group of 42
      medication-free OCD patients as well as 42 healthy controls during a stop-signal
      task. Symptom dimension scores were obtained using the Yale-Brown Obsessive
      Compulsive Scale symptom checklist. OCD patients showed longer stop-signal
      reaction times (SSRT, p < 0.01) and larger stop-N2 amplitudes (p < 0.01) compared
      to healthy controls. Neither the longer SSRT nor the larger stop-N2 scores were
      significantly correlated with symptom severity or present or lifetime OCD
      symptoms in OCD patients. These results indicate that deficient response
      inhibition is a common occurrence in OCD patients that is independent of global
      symptom severity and symptom dimensions. These data support the notion that
      impaired response inhibition may be a general attribute of patients with OCD. 

PMID- 25990065
TI  - Identification of fibrillins as a major component of coronary atherosclerotic
      plaques.
AB  - Fibrillins are two distinct 350 kD RGD-containing glycoproteins found in
      microfibrils in the extracellular matrix. Fibrillin-containing microfibrils are
      required for elastic fiber formation and serve as an anchor for protein binding
      via beta1 and/or alphavbeta3 receptors. Fibrillin-1 is causally linked to
      Marfan's syndrome, which is in part characterized by disruption of the aortic
      media. Fibrillin-2 is causally linked to congenital contractural arachnodactyly,
      which is rarely characterized by cardiovascular symptoms. We hypothesized that
      fibrillins might be present in coronary atherosclerotic plaques and contribute to
      plaque stability. To test this, we examined the expression of fibrillins-1 and -2
      in human coronary arteries and coronary atherectomies. Positive staining for
      fibrillin-1 and fibrillin-2 proteins was observed by immunochemistry in 95% of
      the specimens. Fibrillin-1 was localized to the plaque, adventitia, and
      endothelial cells. Fibrillin-2 stained diffusely in the adventitia and focally in
      the plaque. Neither fibrillin was abundant in the media. Substantial differences
      between the amount and localization of histologically stained elastic fibers and
      fibrillin immunohistochemical staining were noted. By in situ hybridization,
      fibrillin-1 mRNA was localized to smooth muscle cells, endothelial cells, and
      fibroblasts. In spite of the presence of fibrillin-2 antigen by
      immunohistochemistry, fibrillin-2 mRNA was not detected by in situ hybridization.
      These data implicate fibrillins as important components of the atherosclerotic
      plaque. Fibrillins may contribute to plaque stability and act as binding sites
      for other macromolecules within the atherosclerotic lesion. 

PMID- 25990066
TI  - Lipofuscin and lipid oxidation in human coronary endothelium.
AB  - Coronary artery endothelium was studied in 13 human hearts removed in the course
      of heart transplants. Plasma cholesterol ranged from 60 to 240 mg/dl (median
      151). In all cases, abundant endothelial lipid and lipofuscin droplets were
      found, with images of transition between the two types; ultrastructural evidence
      indicated that lipofuscin derived both by fusion of smaller lipofuscin droplets
      as well as by oxidation of lipid droplets. There was no evidence of lipofuscin
      generation by autophagocytosis as seen in other organs. It is concluded that
      endothelial lipofuscin is not "wear-and-tear pigment" but a byproduct of lipid
      oxidation, a process normally carried out by the endothelial cells. In the
      endothelium of human veins, lipofuscin granules were much smaller and rare; this
      points to a biological difference between arterial and venous endothelium. 

PMID- 25990067
TI  - Bilateral Ebstein's Malformation Associated with Multiple Orifices in the
      Atrioventricular Valves.
AB  - Ebstein's malformation involving both atrioventricular valves is a very rare
      entity. We report two cases in which the atrioventricular valves were also
      associated with multiple orifices. The first was an adult with known congenital
      heart disease. The true nature of the valvar malformation, associated with
      atrioventricular septal defect, was only discovered at autopsy. The second case
      was a neonatal heart specimen associated with hypoplastic left ventricle and
      aortic atresia. A review of the literature showed that Ebstein's malformation was
      rarely associated with atrioventricular septal defect. While accessory orifices
      were common in the left atrioventricular valve, they were rarely found in the
      right atrioventricular valve. Our cases, therefore, showed a very rare
      combination of seemingly disparate defects at the level of the atrioventricular
      junction. 

PMID- 25990068
TI  - Vasculopathies of Neurofibromatosis Type 1 (von Recklinghausen Disease).
AB  - Vasculopathies are the least publicized but most important manifestation of
      neurofibromatosis type 1 (NF1, or, von Recklinghausen disease) as the cause of
      morbidity and mortality in children and young adults afflicted with the disease.
      Occlusive or aneurysmal disease of arteries of all sizes may occur almost
      anywhere in the body. Coarctation or segmental hypoplasia of the abdominal aorta
      with or without renal artery ostial stenosis is a common cause of renovascular
      hypertension. Although rare, occlusive coronary artery disease in NF1 may result
      in myocardial infarction and sudden unexpected death. Visceral vasculopathy
      causes ischemic bowel disease; and catastrophic retroperitoneal or abdominal
      hemorrhage has been attributed to spontaneously ruptured arterial aneurysms.
      Peripheral vascular disease in NF1 with limb ischemia requiring an amputation is
      described for the first time here. Scanty information exists in the current
      pathology literature on NF1 vasculopathies, hence the presentation of this
      review. 

PMID- 25990069
TI  - Gastrointestinal vasculitis and vasculitis associated with gastrointestinal
      diseases.
AB  - Vasculitis and the gut may be linked in two different sets of circumstances. In
      one, which is more common, the gut is merely one of the several organ-systems
      affected by systemic vasculitis and vasculitis associated with rheumatic
      connective tissue diseases or inflammatory bowel disease (secondary vasculitis).
      In the other, which is more uncommon, the vasculitis is isolated to the
      gastrointestinal tract (primary vasculitis). In either category, intestinal
      ischemia with hemorrhage, perforation, or gangrene may be the catastrophic
      complications that, even with timely surgical intervention, could still carry a
      high mortality rate. Familiarity with the histopathologic spectrum of primary and
      secondary gastrointestinal vasculitis is a prerequisite for correct
      interpretation of biopsy and surgical resection specimens that will determine the
      appropriate choice of treatment. 

PMID- 25990070
TI  - A comparison of conventional visual and spectrophotometric shade taking by
      trained and untrained dental students.
AB  - BACKGROUND: The aim of this study was to compare the accuracy of shade selection
      using a spectrophotometer with a conventional method using a shade guide for
      'trained' and 'untrained' students. METHODS: The 'trained' group were given a
      presentation and training exercise on colour science and shade selection and the
      'untrained' group were not given any information or training. Each student
      matched the shade of maxillary right central incisor for eight test subjects
      using both methods. Differences in colour (?E) and value (?L) between the natural
      teeth and the shade determined by each method were calculated for both trained
      and untrained students. RESULTS: Overall, the spectrophotometric method was more
      accurate but 'trained' students tended to be more accurate in matching shade
      using the visual method and were significantly better in matching the value
      visually than when using the spectrophotometer. 'Untrained' students matched both
      the shade and the value more accurately when using the spectrophotometer.
      CONCLUSIONS: Within the limits of this study, matching the shade of natural teeth
      using a spectrophotometric device is more accurate than a conventional method
      using a shade guide. However, knowledge and training on colour science and shade
      selection significantly affected the results.

PMID- 25990071
TI  - Plasmonic cavity-apertures as dynamic pixels for the simultaneous control of
      colour and intensity.
AB  - Despite steady technological progress, displays are still subject to inherent
      limitations in resolution improvement and pixel miniaturization because a series
      of colours is generally expressed by a combination of at least three primary
      colour pixels. Here we propose a structure comprising a metal cavity and a
      nanoaperture, which we refer to as a cavity-aperture, to simultaneously control
      the colour and intensity of transmitted light in a single pixel. The metal cavity
      constructs plasmonic standing waves to organize the spatial distribution of
      amplitudes according to wavelength, and the nanoaperture permits light with a
      specific wavelength and amplitude to pass through it, depending on the
      nanoaperature's relative position in the cavity and the polarization state of the
      incident light. Therefore, the cavity-aperture has the potential to function as a
      dynamic colour pixel. This design method may be helpful in developing various
      photonic devices, such as micro-imaging systems and multiplexed sensors. 

PMID- 25990073
TI  - Orchestrating an immune response against cancer with engineered immune cells
      expressing alphabetaTCRs, CARs, and innate immune receptors: an immunological and
      regulatory challenge.
AB  - Over half a century ago, the first allogeneic stem cell transplantation (allo
      SCT) initiated cellular immunotherapy. For several decades, little progress was
      made, and toxicity of allo-SCT remained a major challenge. However, recent
      breakthroughs have opened new avenues to further develop this modality and to
      provide less toxic and equally efficient interventions for patients suffering
      from hematological or solid malignancies. Current novel cellular immune
      interventions include ex vivo expansion and adoptive transfer of tumor
      infiltrating immune cells or administration of drugs which antagonize tolerizing
      mechanisms. Alternatively, transfer of immune cells engineered to express defined
      T cell receptors (TCRs) and chimeric antigen receptors (CARs) has shown its
      potential. A valuable addition to 'engineered' adaptive immunity has emerged
      recently through the improved understanding of how innate immune cells can attack
      cancer cells without substantial side effects. This has enabled the development
      of transplantation platforms with limited side effects allowing early immune
      interventions as well as the design of engineered immune cells expressing innate
      immune receptors. Here, we focus on innate immune interventions and their
      orchestration with TCR- and CAR-engineered immune cells. In addition, we discuss
      how the exploitation of the full potential of cellular immune interventions is
      influenced by regulatory frameworks. Finally, we highlight and discuss
      substantial differences in the current landscape of clinical trials in Europe as
      compared to the USA. The aim is to stimulate international efforts to support
      regulatory authorities and funding agencies, especially in Europe, to create an
      environment that will endorse the development of engineered immune cells for the
      benefit of patients. 

PMID- 25990074
TI  - Increased CCL17 serum levels are associated with improved survival in advanced
      melanoma.
AB  - BACKGROUND: Prognostic factors of melanoma patients with distant metastases
      remain poorly established. This study aimed to compare the prognostic impact of
      putative serum biomarkers, namely S100B, YKL-40 or CCL17, in stage IV melanoma
      patients. PATIENTS AND METHODS: Serum concentrations were analyzed by ELISA.
      Disease-specific survival of 80 patients according to S100B, YKL-40 or CCL17 and
      clinical factors were calculated by univariate Kaplan-Meier survival and
      multivariate analysis. RESULTS: Low serum levels of S100B, high concentrations of
      CCL17 and female gender correlated with improved survival. A trend for favorable
      prognosis was observed for the M categories M1a/b versus M1c according to the
      AJCC classification. No correlation with survival was evident for YKL-40 serum
      levels and age. In multivariate analysis, S100B (HR 2.1; p = 0.005) and CCL17 (HR
      1.8; p = 0.029) had independent prognostic impact. Patients with a combination of
      normal S100B and high CCL17 had a high chance for long-term survival, which was
      43 % after 3 years. CONCLUSION: Serum levels of CCL17 and S100B represent
      independent prognostic markers for melanoma patients with distant metastases.
      These biomarkers were more powerful than the M category according to the AJCC
      classification to indicate overall survival. CCL17 represents a promising
      biomarker upon immune checkpoint blockade in melanoma.

PMID- 25990075
TI  - Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes
      in patients with colorectal cancer.
AB  - Although the development of multi-disciplinary management has improved the
      survival of colorectal cancer (CRC), the prognosis of metastatic CRC patients
      remains poor. Accumulating evidence has demonstrated that immunotherapy with
      cancer vaccines and adoptive T cell transfusions may improve outcomes as an
      adjuvant to current standard CRC treatment. In this phase I/II study, 71 CRC
      patients who underwent radical surgery (stage I-III, n = 46) or palliative
      surgery (stage IV with non-resectable synchronous metastases, n = 25) were
      included. In the first part of this study, sentinel lymph nodes (SLNs) were
      intraoperatively identified in 55 patients (46 with stage I-III CRC and 9 with
      stage IV CRC). SLN-T lymphocytes were expanded ex vivo for a median of 28.5 days
      (range 23-33 days). Thereafter, a median of 153 * 10(6) cells (range 20.7-639.0 *
      10(6)) were transfused. No treatment-related toxicity was observed. In the second
      part of this study, the stage IV patients were routinely followed. The 24-month
      survival rate of the SLN-T lymphocyte group was significantly higher than that of
      the control group: 55.6 versus 17.5% (p = 0.02). The median overall survival of
      the SLN-T lymphocyte and control groups was 28 and 14 months, respectively. Our
      study showed that adjuvant SLN-T lymphocyte immunotherapy is feasible and safe
      for postoperative CRC patients. Additionally, this therapy may improve the long
      term survival of metastatic CRC. Further investigation of the clinical efficacy
      and anti-tumor immunity is warranted.

PMID- 25990077
TI  - Inferior gluteal artery pseudoaneurysm 37 years after transpelvic gunshot wound.

PMID- 25990076
TI  - The "Down the PC" view - A new tool to assess screw positioning in the posterior
      column of the acetabulum.
AB  - INTRODUCTION: Minimal-invasive placement of screws into the posterior column of
      the acetabulum (PC) is challenging. Due to the saddle-shaped curvature of the
      medial cortical border of the PC, the standard fluoroscopic views of the pelvis
      cannot provide the desired safety during screw insertion. The aim of this study
      was to define a view tangentially to the medial cortex of the PC and to evaluate
      its accuracy and inter-observer reproducibility. METHODS: Radio-dense markers on
      the medial cortex of the PC along the axis of a PC screw were brought in line and
      landmarks of the new "Down the PC" view were determined. Kirschner wires were
      placed into the PC of a pelvis composite model and five pelvic cadaver specimens
      in a total of 34 different correct and incorrect positions. Based on either only
      the "Down the PC" view, only the standard views, or a combination of both, three
      fellowship-trained orthopaedic surgeons had to decide if the inserted wires were
      in bone in the posterior column or had exited cortex, and if they penetrated the
      acetabulum. Sensitivity, specificity, and the intra-class correlation coefficient
      were calculated. RESULTS: A view using three radiographic landmarks (pelvic brim,
      medial cortical wall of the body of the ischium, ischial spine) was found.
      Sensitivity and specificity to detect perforation out of the bone were 1.00 and
      0.97 for the "Down the PC" view, 0.46 and 0.97 if only the standard views were
      used, and 1.00 and 0.95 for a combination of both. Sensitivity and specificity to
      detect intra-articular wire placement were 1.00 and 0.96 for the "Down the PC"
      view, 0.72 and 0.95 if only the standard views were used, and 0.94 and 0.99 for a
      combination of both. Inter-observer agreement using only the "Down the PC" view
      was excellent with an ICC of 0.92 for perforation and ICC of 0.82 for intra
      articular wire placement. CONCLUSIONS: The "Down the PC" view is a useful
      addendum in the orthopaedic trauma surgeon's tool box. Using simple landmarks, it
      is easily to reproduce and thereby shows excellent accuracy and inter-observer
      agreement in order to detect medial perforation or intra-articular implant
      position.

PMID- 25990079
TI  - Metal hydride-based materials towards high performance negative electrodes for
      all-solid-state lithium-ion batteries.
AB  - Electrode performances of MgH2-LiBH4 composite materials for lithium-ion
      batteries have been studied using LiBH4 as the solid-state electrolyte, which
      shows a high reversible capacity of 1650 mA h g(-1) with an extremely low
      polarization of 0.05 V, durable cyclability and robust rate capability. 

PMID- 25990080
TI  - Non-pharmacological interventions for agitation in dementia: various strategies
      demonstrate effectiveness for care home residents; further research in home
      settings is needed.

PMID- 25990081
TI  - An Improved Integration of Template-Based and Template-Free Protein Structure
      Modeling Methods and its Assessment in CASP11.
AB  - Most computational protein structure prediction methods are designed for either
      template based or template-free (ab initio) structure prediction. The approaches
      that integrate the prediction capabilities of both template-based modeling and
      template-free modeling are needed to synergistically combine the two kinds of
      methods to improve protein structure prediction. In this work, we develop a new
      method to integrate several protein structure prediction methods including our
      template-based MULTICOM server, our ab initio contact-based protein structure
      prediction method CONFOLD, our multi-template-based model generation tool MTMG,
      and locally installed external Rosetta, I-TASSER and RaptorX protein structure
      prediction tools to improve protein structure prediction of a fullspectrum
      difficulty ranging from easy, to medium and to hard. Our method participated in
      the 11(th) community-wide Critical Assessment of Techniques for Protein Structure
      Prediction (CASP11) in 2014 as MULTICOM-NOVEL server. It was ranked among top 10
      methods for protein tertiary structure prediction according to the official
      CASP11 assessment, which demonstrates that integrating complementary modeling
      methods is useful for advancing protein structure prediction. 

PMID- 25990082
TI  - Effects of Cofactors on Conformation Transition of Random Peptides Consisting of
      a Reduced Amino Acid Alphabet.
AB  - This study aims to explore the structure characteristic of random polypeptides
      constructed by origin early amino acid alphabet, as well as the effects of
      cofactors on conformation transition of random peptides. DNA library R8-4
      encoding VNM random peptides were constructed by small cassette strategy.
      Subsequently, a random polypeptide library was constructed using in vitro
      translation. Expression and purification of VNM random peptides were also
      performed by a conventional method of recombinant. CD spectrum analysis indicated
      that VNM random polypeptides have a secondary structure characteristic of
      protein, such as the content of alpha-helix is greater than 60%, random coil is
      about 20% beta sheet, and beta turn is less than 10%. CD spectrum changed with
      the addition of 10-40 uM ATP and NADP, but slightly changed by NAD; no influence
      was observed with MgSO4. Bis-ANS binding assay indicated that fluorescent
      intensity of bis-ANS was strengthened slightly by 10 VNM random peptides.
      Fluorescent intensity was strengthened fourfold by adding 10-40 uM ATP, NAD, and
      NADH, whereas the inducing effect of NADPH and MgSO4 were negligible. VNM random
      peptides have a classic secondary structure and hydrophobic domain in water
      solution. Moreover, conformation transition and hydrophobic domain could be
      induced by cofactor, indicating the preliminary evidence for the hypothesis that
      "the origin of primitive protein was induced by small molecule." 

PMID- 25990083
TI  - An Overview of Interleukin-17A and Interleukin-17 Receptor A Structure,
      Interaction and Signaling.
AB  - Interleukin-17A (IL-17A) and its receptor (IL-17RA) are prototype members of IL
      17 ligand/receptor family firstly identified in CD4+ T cells, which comprises six
      ligands (IL-17A to IL- 17F) and five receptors (IL-17RA to IL-17RE). IL-17A is
      predominantly secreted by T helper 17 (Th17) cells, and plays important roles in
      the development of autoimmune and inflammatory diseases. IL-17RA is widely
      expressed, and forms a complex with IL-17RC. Binding of IL-17A to this receptor
      complex triggers the activation of several intracellular signaling pathways. In
      this review, we aimed to summarize literature data about molecular features of IL
      17A and IL-17RA from gene to mature protein. We are also providing insight into
      regulatory mechanisms, protein structural conformation, including ligand-receptor
      interaction, and an overview of signaling pathways. Our aim was to compile the
      data on molecular characteristics of IL-17A and IL-17RA which may help in the
      understanding of their functions in health and disease. 

PMID- 25990084
TI  - Heterologous Expression of MeLEA3: A 10 kDa Late Embryogenesis Abundant Protein
      of Cassava, Confers Tolerance to Abiotic Stress in Escherichia coli with
      Recombinant Protein Showing In Vitro Chaperone Activity.
AB  - Late embryogenesis abundant (LEA) proteins are small molecular weight proteins
      involved in acquisition of tolerance to drought, salinity, high temperature,
      cold, and freezing stress in many plants. Previous studies revealed a cDNA
      sequence coding for a 10 kDa atypical LEA protein, named MeLEA3, predicted to be
      located into mitochondria with potential role in salt stress response of cassava
      (Manihot esculenta Crantz). Here we aimed to produce the recombinant MeLEA3
      protein by heterologous expression in Escherichia coli and evaluate the tolerance
      of bacteria expressing this protein under abiotic stress. Our result revealed
      that the recombinant MeLEA3 protein conferred a protective function against heat
      and salt stress in bacterial cells. Also, the recombinant MeLEA3 protein showed
      in vitro chaperone activity by protection of NdeI restriction enzyme activity
      under heat stress. 

PMID- 25990085
TI  - Autoantibody Signatures Combined with Epstein-Barr Virus Capsid Antigen-IgA as a
      Biomarker Panel for the Detection of Nasopharyngeal Carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is prevalent in Southern China and Southeast Asia,
      and autoantibody signatures may improve early detection of NPC. In this study,
      serum levels of autoantibodies against a panel of six tumor-associated antigens
      (p53, NY-ESO-1, MMP-7, Hsp70, Prx VI, and Bmi-1) and Epstein-Barr virus capsid
      antigen-IgA (VCA-IgA) were tested by enzyme-linked immunosorbent assay in a
      training set (220 NPC patients and 150 controls) and validated in a validation
      set (90 NPC patients and 68 controls). We used receiver-operating characteristics
      (ROC) to calculate diagnostic accuracy. ROC curves showed that use of these 6
      autoantibody assays provided an area under curve (AUC) of 0.855 [95% confidence
      interval (CI), 0.818-0.892], 68.2% sensitivity, and 90.0% specificity in the
      training set and an AUC of 0.873 (95% CI, 0.821-0.925), 62.2% sensitivity, and
      91.2% specificity in the validation set. Moreover, the autoantibody panel
      maintained diagnostic accuracy for VCA-IgA-negative NPC patients [0.854 (0.809
      0.899), 67.8%, and 90.0% in the training set; 0.879 (0.815-0.942), 67.4%, and
      91.2% in the validation set]. Importantly, combination of the autoantibody panel
      and VCA-IgA improved diagnostic accuracy for NPC versus controls compared with
      the autoantibody panel alone [0.911 (0.881-0.940), 81.4%, and 90.0% in the
      training set; 0.919 (0.878-0.959), 78.9%, and 91.2% in the validation set), as
      well as for early-stage NPC (0.944 (0.894-0.994), 87.9%, and 94.0% in the
      training set; 0.922 (0.808-1.000), 80.0%, and 92.6% in the validation set]. These
      results reveal autoantibody signatures in an optimized panel that could improve
      the identification of VCA-IgA-negative NPC patients, may aid screening and
      diagnosis of NPC, especially when combined with VCA-IgA.

PMID- 25990086
TI  - Metformin Use and Lung Cancer Risk--Letter.

PMID- 25990087
TI  - Prediagnostic Obesity and Physical Inactivity Are Associated with Shorter
      Telomere Length in Prostate Stromal Cells.
AB  - Obesity and inactivity have been associated with advanced-stage prostate cancer,
      and poor prostate cancer outcomes, though the underlying mechanism(s) is unknown.
      To determine whether telomere shortening, which has been associated with lethal
      prostate cancer, may be a potential underlying mechanism, we prospectively
      evaluated the association between measures of adiposity, physical activity, and
      telomere length in 596 participants in the Health Professionals Follow-up Study,
      who were surgically treated for prostate cancer. Using tissue microarrays, we
      measured telomere length in cancer and benign cells using a telomere-specific
      FISH assay. Adiposity and activity were assessed via questionnaire within 2 years
      of diagnosis. Adjusting for age, pathologic stage, and grade, the median and SD
      of the per cell telomere signals were determined for each man for stromal cells
      and cancer cells by adiposity and activity categories. Overweight/obese men (54%)
      were similar to normal weight men on most factors, but had higher Gleason sum and
      lower activity levels. Overweight/obese men had 7.4% shorter telomeres in stromal
      cells than normal weight men (P = 0.06). The least active men had shorter
      telomeres in stromal cells than more active men (Ptrend = 0.002). Men who were
      overweight/obese and the least active had the shortest telomeres in stromal cells
      (20.7% shorter; P = 0.0005) compared with normal weight men who were the most
      active. Cancer cell telomere length and telomere length variability did not
      differ by measures of adiposity or activity. Telomere shortening in prostate
      cells may be one mechanism through which lifestyle influences prostate cancer
      risk and outcomes.

PMID- 25990090
TI  - Scant evidence on the effectiveness of metformin in type 2 diabetes.

PMID- 25990088
TI  - Bacterial Prostatitis Enhances 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine
      (PhIP)-Induced Cancer at Multiple Sites.
AB  - Dietary carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP), and chronic inflammation have each been implicated as etiologic agents in
      prostate cancer. We hypothesized that bacterial prostatitis would accelerate PhIP
      induced preinvasive lesions in the rat prostate. Male Fischer 344 rats were
      assigned into 4 groups: Control (untreated), PhIP (200 ppm in the diet for 20
      weeks), Escherichia coli (E. coli, prostatic inoculation in week 10), or PhIP +
      E. coli. Study animals were monitored for a total of 52 weeks and were euthanized
      as necessary based on strict criteria for health status and tumor burden. Animals
      treated with E. coli initially developed acute and chronic inflammation in all
      lobes of the prostate, whereas inflammation was observed predominantly in the
      ventral lobe at time of death. PhIP + E. coli-treated animals exhibited a marked
      decrease in survival compared with PhIP-alone-treated animals as a result of an
      increase in the number of invasive cancers that developed at multiple sites,
      including the skin, small intestine, and Zymbal's gland. Despite their earlier
      mortality, PhIP + E. coli-treated animals developed an increased average number
      of precancerous lesions within the prostate compared with PhIP-treated animals,
      with a significantly increased Ki-67 index. Multiplexed serum cytokine analysis
      indicated an increase in the level of circulating IL6 and IL12 in PhIP + E. coli
      treated animals. Elevated serum IL6 levels correlated with the development of
      precancerous lesions within the prostate. These results suggest that bacterial
      infections and dietary carcinogens, two conceivably preventable cancer risk
      factors, may synergistically promote tumorigenesis.

PMID- 25990089
TI  - Liver sharing and organ procurement organization performance under redistricted
      allocation.
AB  - Concerns have been raised that optimized redistricting of liver allocation areas
      might have the unintended result of shifting livers from better-performing to
      poorer-performing organ procurement organizations (OPOs). We used liver simulated
      allocation modeling to simulate a 5-year period of liver sharing within either 4
      or 8 optimized districts. We investigated whether each OPO's net liver import
      under redistricting would be correlated with 2 OPO performance metrics (observed
      to expected liver yield and liver donor conversion ratio), along with 2 other
      potential correlates (eligible deaths and incident listings above a Model for End
      Stage Liver Disease score of 15). We found no evidence that livers would flow
      from better-performing OPOs to poorer-performing OPOs in either redistricting
      scenario. Instead, under these optimized redistricting plans, our simulations
      suggest that livers would flow from OPOs with more-than-expected eligible deaths
      toward those with fewer-than-expected eligible deaths and that livers would flow
      from OPOs with fewer-than-expected incident listings to those with more-than
      expected incident listings; the latter is a pattern that is already established
      in the current allocation system. Redistricting liver distribution to reduce
      geographic inequity is expected to align liver allocation across the country with
      the distribution of supply and demand rather than transferring livers from better
      performing OPOs to poorer-performing OPOs.

PMID- 25990091
TI  - Viral protein R of HIV type-1 induces retrotransposition and upregulates
      glutamate synthesis by the signal transducer and activator of transcription 1
      signaling pathway.
AB  - Viral protein R (Vpr) of HIV-1 plays an important role in viral replication in
      macrophages. Various lines of evidence suggest that expression of Vpr in
      macrophages causes immunopathogenesis; however, the underlying mechanism is not
      yet fully understood. In this study, it was shown that recombinant Vpr (rVpr)
      induces retrotransposition of long interspersed element-1 in RAW264.7, a
      macrophage-like cell line, and activates reverse transcriptase-dependent
      immunotoxic cascades including production of IFN-beta and phosphorylation of
      signal transducer and activator of transcription 1 (STAT1). Knockout experiments
      based on the CRISPR/Cas9 nickase system further demonstrated that cyclic
      guanosine monophosphate-adenosine monophosphate synthase (cGAS) and stimulator of
      interferon gene (STING) are responsible for IFN-beta production and STAT1
      phosphorylation, respectively. Moreover, rVpr was found to increase production of
      glutaminase C, a regulator of glutamate synthesis, which is also dependent on the
      cGAS-STING pathway. Taken together with reports that glutaminase C is involved in
      the pathogenesis of HIV-associated neurocognitive disorder (HAND) and that Vpr is
      detectable in the cerebrospinal fluid of HIV-1-positive patients, a possible role
      of Vpr-induced L1-RTP and immunotoxic cascades in the development of HAND is
      discussed. 

PMID- 25990092
TI  - Thermochemical study of amino acid imprinted polymer films.
AB  - Molecularly imprinted polymers provide an alternative to traditional methods of
      amino acid analysis. The imprinted polymers are more robust and significantly
      less expensive than, for example, ELISA analysis. Amino acid imprinted nylon-6
      thin films were studied by differential scanning calorimetry and scanning
      electron microscopy. Endothermic peaks were observed for imprinted films at
      temperatures higher than that for pure nylon, indicating the formation of a more
      ordered, hydrogen bonded polymer. Removal of the amino acid from the imprinted
      film resulted in reversion to the peak observed for pure nylon-6. Additives, beta
      cyclodextrin and multiwalled carbon nanotubes, were added to the imprinted
      polymer solutions as a means to increase the porosity of the films. These studies
      resulted in alternative morphologies and calorimetric results that provide
      additional functionalities and applications for imprinted polymers.

PMID- 25990093
TI  - Utility of cardiac computed tomography for evaluation of pannus in mechanical
      aortic valve.
AB  - The clinical significance of pannus detected on computed tomography (CT) has not
      yet been investigated. The purposes of this study were to investigate the
      clinical significance of pannus detected on cardiac CT in patients who underwent
      aortic valve replacement (AVR) with mechanical valves, and to determine
      predictors for pannus severity. A total of 92 patients who underwent cardiac CT
      and TTE and who had undergone mechanical AVR were included. The geometric orifice
      area (GOA), the presence of limitation of motion (LOM) and pannus were evaluated
      on CT. The GOA, presence of LOM, and presence and severity of pannus were
      compared with echocardiographic parameters. Logistic regression analysis was
      performed to determine the predictors for pannus severity. The GOA on CT
      positively correlated with effective orifice area on TTE (r = 0.733, P < 0.0001).
      Pannus was found in 77.2% and LOM in 14.0%. With increasing pannus severity, mean
      transvalvular pressure gradient (PG) was significantly higher (P < 0.0001).
      Patients with elevated PG showed a smaller GOA, a higher incidence of pannus,
      more severe pannus and LOM than patients with normal PG (P < 0.05). Small valve
      size (<=19 mm), Carbomedics valve, rheumatic etiology, and young age at AVR
      (<48.8 years) were independent predictors of moderate to severe pannus (P <
      0.05). Cardiac CT is helpful in the evaluation of pannus formation in patients
      with mechanical aortic valves. Moderate to severe pannus formation frequently
      occurred in patients with small mechanical valve size, Carbomedics valves,
      rheumatic heart disease and young age at AVR.

PMID- 25990094
TI  - Chronic HBV-infected subjects older than 35 years with persistently normal ALT
      and ultrasound, despite high viral load do not have significant fibrosis.

PMID- 25990095
TI  - Rush to judgment: the STI-treatment trials and HIV in sub-Saharan Africa.
AB  - INTRODUCTION: The extraordinarily high incidence of HIV in sub-Saharan Africa led
      to the search for cofactor infections that could explain the high rates of
      transmission in the region. Genital inflammation and lesions caused by sexually
      transmitted infections (STIs) were a probable mechanism, and numerous
      observational studies indicated several STI cofactors. Nine out of the ten
      randomized controlled trials (RCTs), however, failed to demonstrate that treating
      STIs could lower HIV incidence. We evaluate all 10 trials to determine if their
      design permits the conclusion, widely believed, that STI treatment is ineffective
      in reducing HIV incidence. DISCUSSION: Examination of the trials reveals critical
      methodological problems sufficient to account for statistically insignificant
      outcomes in nine of the ten trials. Shortcomings of the trials include weak
      exposure contrast, confounding, non-differential misclassification, contamination
      and effect modification, all of which consistently bias the results toward the
      null. In any future STI-HIV trial, ethical considerations will again require weak
      exposure contrast. The complexity posed by HIV transmission in the genital
      microbial environment means that any future STI-HIV trial will face confounding,
      non-differential misclassification and effect modification. As a result, it is
      unlikely that additional trials would be able to answer the question of whether
      STI control reduces HIV incidence. CONCLUSIONS: Shortcomings in published RCTs
      render invalid the conclusion that treating STIs and other cofactor infections is
      ineffective in HIV prevention. Meta-analyses of observational studies conclude
      that STIs can raise HIV transmission efficiency two- to fourfold. Health policy
      is always implemented under uncertainty. Given the known benefits of STI control,
      the irreparable harm from not treating STIs and the likely decline in HIV
      incidence resulting from STI control, it is appropriate to expand STI control
      programmes and to use funds earmarked for HIV prevention to finance those
      programmes.

PMID- 25990097
TI  - Alemtuzumab Induced Thyroid Disease in Multiple Sclerosis: A Review and Approach
      to Management.
AB  - Alemtuzumab, an anti-CD52 monoclonal antibody, was recently approved for
      treatment of MS in Canada, having shown to significantly reduce relapses and
      disability in patients, particularly those who relapsed despite first line
      treatment. Offsetting its benefit however, is the development of novel secondary
      autoimmune disease, particularly affecting the thyroid gland in up to 36% of
      patients. The incidence of Alemtuzumab induced thyroid dysfunction (AITD) will
      likely rise as alemtuzumab becomes more widely used for treating MS. We review
      the clinical and investigational cues that help delineate the aetiology and
      management of thyrotoxicosis and hypothyroidism in ATID. AITD can be easily
      managed and we present a simple approach for its evaluation and management by
      neurologists that should be implemented prior to considering a referral to an
      internist or endocrinologist for further opinion or treatment. 

PMID- 25990096
TI  - Filamentous aggregations of phosphorylated alpha-synuclein in Schwann cells
      (Schwann cell cytoplasmic inclusions) in multiple system atrophy.
AB  - BACKGROUND: The histological hallmark of multiple system atrophy (MSA) is the
      presence of filamentous aggregations of phosphorylated alpha-synuclein in
      oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). Although
      GCIs can occur widely in the central nervous system, accumulation of
      phosphorylated alpha-synuclein in Schwann cells has not been reported in MSA. We
      immunohistochemically examined the cranial and spinal nerves, peripheral ganglia
      and visceral autonomic nervous system of patients with MSA (n = 14) and control
      subjects (n = 20). RESULTS: In MSA, accumulation of phosphorylated alpha
      synuclein was found in the cytoplasm of Schwann cells. These Schwann cell
      cytoplasmic inclusions (SCCIs) were also immunopositive for ubiquitin and p62.
      SCCIs were found in 12 of 14 patients with MSA (85.7 %). They were most frequent
      in the anterior nerve of the sacral cord and, to a lesser extent, in the cranial
      nerves (oculomotor, glossopharyngeal-vagus and hypoglossal nerves), and spinal
      and sympathetic ganglia. SCCIs were rarely found in the visceral organs.
      Immunoelectron microscopy demonstrated that the SCCIs consisted of abnormal
      filaments, 15-20 nm in diameter. No such inclusions were found in controls.
      CONCLUSION: The present findings indicate that Schwann cells are also involved in
      the disease process of MSA.

PMID- 25990098
TI  - Corneal collagen cross-linking for infectious keratitis: an update of clinical
      studies.
AB  - Collagen cross-linking (CXL) with ultraviolet light-activated riboflavin is a
      corneal surface procedure developed for the treatment of keratoconus and corneal
      ectasia. With the known microbicidal and corneal stiffening effects of
      ultraviolet irradiation and photoactivated riboflavin, it has recently been
      introduced for the management of infectious keratitis, especially for ulcers
      resistant to antimicrobial therapy or associated with corneal melting. Various
      authors have attempted to use CXL as an adjunctive, salvage or even as the sole
      treatment for infectious corneal ulcers. The aim of this review was to provide a
      summary of the clinical studies in the literature. It is worth noting that there
      is still no consensus on the treatment protocol of CXL against infectious
      keratitis. The disparities in outcome measures, treatment protocol and study
      design can confound the interpretation and hamper the generalization of the study
      results. Based on current evidence, the role of CXL in infectious keratitis
      remained unclear despite the reported success in some clinical cases. Further
      investigations are warranted concerning the efficacy and safety of treating
      infectious keratitis with CXL. 

PMID- 25990100
TI  - Bilateral sciatic neuropathy misdiagnosed as critical illness neuropathy: a case
      report.

PMID- 25990099
TI  - Urinary Tract Stones and Osteoporosis: Findings From the Women's Health
      Initiative.
AB  - Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent,
      serious conditions for postmenopausal women. Men with kidney stones are at
      increased risk of osteoporosis; however, the relationship of urinary tract stones
      to osteoporosis in postmenopausal women has not been established. The purpose of
      this study was to determine whether urinary tract stones are an independent risk
      factor for changes in bone mineral density (BMD) and incident fractures in women
      in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in
      the Observational Study and Clinical Trials of the WHI with information on
      urinary tract stones status: 9856 of these women reported urinary tract stones at
      baseline and/or incident urinary tract stones during follow-up. Cox regression
      models were used to determine the association of urinary tract stones with
      incident fractures and linear mixed models were used to investigate the
      relationship of urinary tract stones with changes in BMD that occurred during
      WHI. Follow-up was over an average of 8 years. Models were adjusted for
      demographic and clinical factors, medication use, and dietary histories. In
      unadjusted models there was a significant association of urinary tract stones
      with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in
      covariate adjusted analyses, urinary tract stones were not significantly related
      to changes in BMD at any skeletal site or to incident fractures. In conclusion,
      urinary tract stones in postmenopausal women are not an independent risk factor
      for osteoporosis.

PMID- 25990101
TI  - Erratum to: Management of headache disorders in the Emergency Department setting.

PMID- 25990102
TI  - The prevalence of restless legs syndrome in Edirne and its districts concomitant
      comorbid conditions and secondary complications.
AB  - We aimed to determine the prevalence and risk factors of restless legs syndrome
      in Edirne and its districts, located in Western Thrace, which is the most western
      part of Turkey. In this study, 4003 individuals who could communicate and agreed
      to participate in the study were evaluated. To obtain the data from the
      applicants in 30 Family Health Centres in Edirne and its districts, a face-to
      face questionnaire that consisted of 54 questions was prepared by the
      researchers. The questionnaire included general information, questions to
      evaluate potential concomitant comorbid conditions and questions regarding the
      symptomatology used in restless legs syndrome (RLS) diagnosis, as well as
      questions to evaluate insomnia and tension-type headache secondary to insomnia
      according to the ICD-II Criteria (International Classification of Sleep Disorders
      II Criteria). Of 4003 individuals, 282 were diagnosed with RLS according to the
      questionnaire results from Edirne and its districts, and the prevalence of RLS
      was 7%. Approximately, 47.9% of the patients with RLS were male, and 52.1% were
      female, which was not significantly different (p > 0.05). Anaemia was identified
      in 41.1 % of the cases and control group was detected in 19.4 %, which was
      significantly different (p < 0.001). Secondary insomnia was identified in 64.2%
      of the cases with RLS and was not detected in 35.8%, which was significantly
      different (p < 0.001). RLS prevalence studies will increase the awareness of the
      community and provide early diagnosis and treatment, as well as serve as a basis
      to reduce morbidity and improve the quality of life.

PMID- 25990103
TI  - Brainstem glioblastoma in a patient with secondary progressive multiple
      sclerosis.

PMID- 25990104
TI  - Intravenous thiotepa for treatment of breast cancer-related leptomeningeal
      carcinomatosis: case series.
AB  - Leptomeningeal carcinomatosis (LMC) secondary to metastatic breast cancer (MBC)
      has increased in incidence with improved systemic disease control. Current
      treatment options include radiation therapy (to symptomatic sites) and systemic
      treatment [intrathecal (IT) or intravenous (IV) chemotherapy]. Methotrexate
      (MTX), thiotepa and cytarabine are the most commonly used IT agents, while high
      dose MTX is the most common IV regimen. While IT treatments are generally well
      tolerated, complications like chemical meningitis, leukoencephalopathy, etc.
      occur. LMC may cause a breakdown in the blood-brain barrier and thus allow
      systemic agents to penetrate; however, efficacy is reported only for agents
      administered at high doses (MTX). We report our institution's experience in using
      IV thiotepa as treatment for LMC secondary to MBC. We conducted a retrospective
      chart review of 13 patients with MBC who developed LMC and treated with IV
      thiotepa at our institution. It was administered at 40 mg/m(2) every 21 days;
      median number of thiotepa cycles administered was 5 with the major dose-limiting
      toxicity being myelosuppression. Four had partial response, 3 had stable disease
      and 6 had progressive disease. The 6-month survival rate was 69 % and 1-year
      survival rate was 31 %. Despite retrospective nature of our case series, we found
      the use of IV thiotepa as sole treatment for LMC in patients with MBC to be well
      tolerated, easily administered in the ambulatory setting, and with efficacy
      comparable to the other chemotherapeutic agents commonly used in the treatment of
      LMC. This regimen warrants further investigation in prospective studies.

PMID- 25990105
TI  - Metronidazole-induced central and peripheral nervous system toxicity.

PMID- 25990106
TI  - Temoporfin improves efficacy of photodynamic therapy in advanced biliary tract
      carcinoma: A multicenter prospective phase II study.
AB  - Photodynamic therapy using porfimer (P-PDT) improves palliation and survival in
      nonresectable hilar bile duct cancer. Tumoricidal penetration depth of temoporfin
      PDT (T-PDT) is twice that of P-PDT. In a single-arm phase II study we
      investigated the safety, efficacy, survival time, and adverse events of T-PDT
      compared with previous data on P-PDT. Twenty-nine patients (median 71 [range 47
      88] years) with nonresectable hilar bile duct cancer were treated with T-PDT
      (median 1 [range 1-4] sessions) plus stenting and followed up every 3 months. The
      PDT was well tolerated. In patients with occluded segments at baseline (n=28) a
      reopening of a median of 3 (range 1-7) segments could be achieved: n=16 local
      response and n=11 stable local disease, one progressive disease. Cholestasis and
      performance significantly improved when impaired at baseline. Time to local tumor
      progression was a median of 6.5 (2.7-41.0) months. Overall survival time was a
      median of 15.4 (range 4.4-62.4) months. Patients died from tumor progression
      (55%), cholangitis (18%), pneumonia (7%), hemobilia (7%), esophagus variceal
      hemorrhage (3%), and vascular diseases (10%). Adverse events were cholangitis
      (n=4), liver abscess (n=2), cholecystitis (n=2), phototoxic skin (n=5), and
      injection site reactions (n=7). Compared to previous P-PDT, T-PDT shows prolonged
      time to local tumor progression (median 6.5 versus 4.3 months, P<0.01), fewer PDT
      treatments needed (median 1 versus 3, P<0.01), a higher 6-month survival rate
      (83% versus 70%, P<0.01), and a trend for longer overall median survival (15.4
      versus 9.3 months, P=0.72) yet not significantly different. The risk of adverse
      events is not increased except for (avoidable) subcutaneous phototoxicity at the
      injection site. CONCLUSION: Temoporfin-PDT can safely be delivered to hilar bile
      duct cancer patients and results in prolonged patency of hilar bile ducts, a
      trend for longer survival time, and similar palliation as with P-PDT.

PMID- 25990107
TI  - Effect of Ionic Conductivity on Response Speed of SrTiO3-Based All-Solid-State
      Electric-Double-Layer Transistor.
AB  - An all-solid-state electric-double-layer transistor (EDLT) with a Y-stabilized
      ZrO2 (YSZ) proton conductor/SrTiO3 (STO) single crystal has been fabricated to
      investigate ionic conductivity effect on the response speed, which should be a
      key parameter for development of next-generation EDLTs. The drain current
      exhibited a 4-order-of-magnitude increment by electrostatic carrier doping at the
      YSZ/STO interface due to ion migration, and the behavior strongly depended on the
      operation temperature. An Arrhenius-type plot of the ionic conductivity
      (sigma(i)) in the YSZ and t(c)-1, which is a current-rise time needed for charge
      accumulation at the YSZ/STO interface, shows a synchronized variation, indicating
      a proportional relationship between the two parameters. Analysis of the sigma(i)
      t(c) diagram shows that, in contrast to conventional EDLTs, the response speed
      should reach picosecond order at room temperature by using extreme
      miniaturization and superionic conductors. Furthermore, the diagram indicates
      that plenty of solid electrolytes, which have not been used due to the lack of
      criteria for evaluation, can be a candidate for all-solid-state EDLTs exceeding
      the carrier density of conventional EDLTs, even though the response speed becomes
      comparably lower than those of FETs.

PMID- 25990109
TI  - Emerging adults' use of alcohol and social networking sites during a large street
      festival: A real-time interview study.
AB  - BACKGROUND: Emerging adults have high rates of heavy episodic drinking (binge
      drinking) and related risks including alcohol-impaired driving. To understand
      whether social networking sites (SNSs) used on mobile devices represent a viable
      platform for real-time interventions, this study measured emerging adults' use of
      two popular SNSs (Facebook and Twitter) during the Mifflin Street Block Party.
      This annual festival is held in Madison, Wisconsin and is known for high alcohol
      consumption. FINDINGS: Event attendees ages 18-23 years were recruited by young
      adult research assistants (>21 years). Participants completed a brief in-person
      interview assessing drinking intensity, use of SNSs, and use of SNSs to plan
      transportation. Analyses included t-tests, chi-squared tests, and Fisher's exact
      tests. At the event, nearly all of the 200 participants (97 %) consumed alcohol
      and 18 % met criteria for heavy episodic drinking. Approximately one-third of
      participants had used Facebook or Twitter on the day of the event. Facebook use
      (23 %) was more prevalent than Twitter use (18 %), especially among heavy
      episodic drinkers. Use of either SNS was 41 % among females and 24 % among males
      (chi (2)=6.01; df=1; p=0.01). Plans to use a SNS to arrange transportation were
      relatively uncommon (4 %), but this was more frequent among heavy episodic
      drinkers (11 %) compared to non-heavy episodic drinkers (2 %) (Fisher's exact
      p=0.02). CONCLUSIONS: These results indicate that SNSs are used during alcohol
      consumption and warrant exploration as a way to facilitate connections to
      resources like safe ride services.

PMID- 25990108
TI  - Preclinical good laboratory practice-compliant safety study to evaluate
      biodistribution and tumorigenicity of a cartilage advanced therapy medicinal
      product (ATMP).
AB  - BACKGROUND: The clinical development of advanced therapy medicinal products
      (ATMPs), a new class of drugs, requires initial safety studies that deviate from
      standard non-clinical safety protocols. The study provides a strategy to address
      the safety aspects of biodistribution and tumorigenicity of ATMPs under good
      laboratory practice (GLP) conditions avoiding cell product manipulation.
      Moreover, the strategy was applied on a human ATMP for cartilage repair. METHODS:
      The testing strategy addresses biodistribution and tumorigenicity using a multi
      step analysis without any cell manipulation to exclude changes of test item
      characteristics. As a safeguard measurement for meeting regulatory expectations,
      the project design and goals were discussed continuously with the regulatory
      authority using a staggered scientific advice concept. Subsequently, the strategy
      was applied to co.don chondrosphere(r) (huChon spheroid), a tissue-engineered
      matrix-free ATMP of human normal chondrocytes. In both the biodistribution and
      tumorigenicity studies, huChon spheroids were implanted subcutaneously into 40
      immunodeficient mice. Biodistribution was studied 1 month after implantation. A
      skin disc containing the huChon spheroid, two surrounding skin rings and selected
      organs were analyzed by validated, gender-specific, highly-sensitive triplex qPCR
      and by immunohistochemistry (IHC). RESULTS: No human DNA was detected in distant
      skin rings and analyzed organs. IHC revealed no direct or indirect indications of
      cell migration. Tumorigenicity was assessed 6 months after huChon spheroid
      implantation by palpation, macroscopic inspection, histology and IHC. No mice
      from the huChon spheroid group developed a tumor at the implantation site. In two
      mice, benign tumors were detected that were negative for HLA-ABC, suggesting that
      they were of spontaneous murine origin. CONCLUSIONS: In summary, the presented
      strategy using a multi-step analysis was confirmed to be suitable for safety
      studies of ATMPs.

PMID- 25990111
TI  - Expanding forms of scholarship.

PMID- 25990113
TI  - Experimental observation of anomalous thermal radiation from a three-dimensional
      metallic photonic crystal.
AB  - We report some striking results on thermal radiation properties of a resonantly
      coupled cavity photonic crystal (PhC) at elevated temperatures (T = 400-900 K).
      We experimentally found that at resonant wavelengths, lambda = 1.1, 1.64, 2.85
      MUm, the PhC emission is spectrally selective, quasi-coherent, directional, and
      shows significant deviation from Planck's blackbody law at equilibrium. The
      presence of non-equilibrium effects, driven by strong thermal excitation and
      cavity resonance, may be the major cause for our experimental observation. 

PMID- 25990110
TI  - Abdominal wall hernia in cirrhotic patients: emergency surgery results in higher
      morbidity and mortality.
AB  - BACKGROUND: Patients with cirrhosis have a high incidence of abdominal wall
      hernias and carry an elevated perioperative morbidity and mortality. The optimal
      surgical management strategy as well as timing of abdominal hernia repair remains
      controversial. METHODS: A cohort study of 67 cirrhotic patients who underwent
      hernia repair during the period of January 1998-December 2009 at the University
      Hospital of Sao Paulo were included. After meeting study criteria, a total of 56
      patients who underwent 61 surgeries were included in the final analysis. Patient
      characteristics, morbidity (Clavien score), mortality, Child-Turcotte-Pugh score,
      MELD score, use of prosthetic material, and elective or emergency surgery have
      been analysed with regards to morbidity and 30-day mortality. RESULTS: The median
      MELD score of the patient population was 14 (range: 6 to 24). Emergency surgery
      was performed in 34 patients because of ruptured hernia (n = 13), incarceration
      (n = 10), strangulation (n = 4), and skin necrosis or ulceration (n = 7).
      Elective surgery was performed in 27 cases. After a multivariable analysis,
      emergency surgery (OR 7.31; p 0.017) and Child-Pugh C (OR 4.54; p 0.037) were
      risk factors for major complications. Moreover, emergency surgery was a unique
      independent risk factor for 30-day mortality (OR 10.83; p 0.028). CONCLUSIONS:
      Higher morbidity and mortality are associated with emergency surgery in advanced
      cirrhotic patients. Therefore, using cirrhosis as a contraindication for hernia
      repair in all patients may be reconsidered in the future, especially after
      controlling ascites and in those patients with hernias that are becoming
      symptomatic or show signs of possible skin necrosis and rupture. Future
      prospective randomized studies are needed to confirm this surgical strategy.

PMID- 25990114
TI  - 2014 ICHLNRRA intercomparison of radon/thoron gas and radon short-lived decay
      products measuring instruments in the NRPI Prague.
AB  - During the Eighth International Conference on High Levels of Natural Radiation
      and Radon Areas held in autumn 2014 at Prague, the third intercomparison of
      radon/thoron gas and radon short-lived decay products measurement instruments was
      organised by and held at the Natural Radiation Division of the National Radiation
      Protection Institute (NRPI; SURO v.v.i.) in Prague. The intercomparison was newly
      focussed also on continuous monitors with active sampling adapters capable to
      distinguish radon/thoron gas in their mix field.The results of radon gas
      measurements carried out in the big NRPI radon chamber indicated very well an
      average deviation of up to 5 % from the reference NRPI value for 80 % of all the
      exposed instruments. The results of equilibrium equivalent concentration
      continuous monitors indicated an average deviation of up to 5 % from the
      reference NRPI value for 40 % of all the exposed instruments and their ~8-10 %
      shift compared with the NRPI. The results of investigated ambient conditions upon
      response of exposed continuous monitors indicated influence of aerosol changes
      upon response of radon monitors with an active air sampling adapters through the
      filter, only. The exposures of both radon/thoron gas discriminative continuous
      monitors and passive detectors have been indicated inconsistent results: on one
      hand, their excellent agreement up to several per cent for both the gases, and on
      the other hand, systematic unsatisfactory differences up to 40 %. Additional
      radon/thoron exercises are recommended to improve both the instruments themselves
      and quality of their operators.

PMID- 25990115
TI  - The portable device for continual measurement of radon progenies on filter using
      the detector Timepix.
AB  - In this article, a portable device was presented for continual measuring of
      equilibrium equivalent concentration (EEC) of (222)Rn based on the Timepix
      detector with 300-um-thick active layer. In order to have a portable device, a
      filtration head was developed for collecting short-lived radon progenies attached
      on aerosols. The short-lived progenies are estimated from analysing alphas from
      decay of (218,214)Po from Millipore filter after termination of filtration.
      Comparison with beta measurement was done as well. The dependence of EEC on an
      air flow and filtration time was studied. The low-level detection limit for EEC
      was estimated from the last 10 min of 3-h decay measurement and was found in the
      range of 40-70 Bq m(-3). EEC was measured in National Radiation Protection
      Institute radon chamber, and results were compared with the commercial detector
      Fritra4. 

PMID- 25990116
TI  - Glucose breath test and Crohn's disease: Diagnosis of small intestinal bacterial
      overgrowth and evaluation of therapeutic response.
AB  - OBJECTIVE: Small intestinal bacterial overgrowth (SIBO) is characterized by an
      abnormal proliferation of bacterial species in the small bowel. It has been shown
      that patients with Crohn's disease (CD) have a higher risk of SIBO development.
      The aim of the present study was to investigate SIBO prevalence in CD patients,
      possible clinical predictors of SIBO development and response to antibiotic
      therapy. MATERIAL AND METHODS: Sixty-eight patients (42 male, 26 female; mean age
      49.3 +/- 12.8 years) with CD reporting abdominal complaints were prospectively
      evaluated for SIBO with H2/CH4 glucose breath test (GBT). RESULTS: Of the 68
      patients enrolled, 18 (26.5%) tested positive for SIBO. Patients with SIBO
      exhibited increased stool frequency and significant reduction of stool solidity
      (p = 0.014), were older than patients tested negative to GBT (54.3 +/- 13.0 years
      vs. 47.5 +/- 12.3 years, p = 0.049), reported a longer history of CD (21.2 +/-
      10.3 years vs. 15.7 +/- 10.2 years, p = 0.031) and showed a significant higher
      frequency of prior surgery (p = 0.001), revealing an association of number of
      surgical procedures (OR = 2.8315, 95% CI = 1.1525-6.9569, p = 0.023) with SIBO.
      Breath test normalization occurred in 13/15 patients evaluated after antibiotic
      and probiotic therapy. Although vitamin B12 levels were lower in patients with
      SIBO (p = 0.045) and a significant improvement was found after treatment (p =
      0.011), this could be due to the heterogeneity, regarding vitamin B12 treatment,
      in our cohort. CONCLUSION: SIBO is a frequent but underestimated condition in CD,
      which often mimics acute flare, effectively identified with GBT and could be
      treated with a combined antibiotic and probiotic therapy.

PMID- 25990118
TI  - Cardiovascular pathology: Past, present, and future achievements.

PMID- 25990119
TI  - Working formulation nomenclature of heart transplant pathology: A retrospective
      evaluation of 1037 endomyocardial biopsies.
AB  - Working Formulation (WF) was recently introduced by the International Society for
      Heart Transplantation to grade acute cellular rejection, as well as additional
      lesions observed in endomyocardial biopsies (EMBs). The aim of this study was to
      evaluate the actual advantages of this grading system in terms of feasibility and
      predictive value. To this purpose, we reclassified 1037 EMBs performed in our
      heart transplantation units according to the WF. Our results show that multifocal
      mild rejection (grade IA), when worsening, tends to progress to multifocal
      moderate (3A), whereas diffuse mild (1B) generally worsens to diffuse moderate
      (3B), thus following the same focal or diffuse pattern. Unifocal moderate
      rejection (grade 2) has a peculiar behavior, in that it almost always resolves,
      though in our units it is treated the same way as is grade 113. Finally, we found
      a significant relationship between Quilty B effect and chronic rejection. In
      conclusion, this retrospective study shows that WF is effective in using both
      qualitative and quantitative criteria and, particularly, in separating focal and
      diffuse forms of rejection and devoting a distinct grade to unifocal moderate
      rejection. 

PMID- 25990117
TI  - Harnessing cross-species alignment to discover SNPs and generate a draft genome
      sequence of a bighorn sheep (Ovis canadensis).
AB  - BACKGROUND: Whole genome sequences (WGS) have proliferated as sequencing
      technology continues to improve and costs decline. While many WGS of model or
      domestic organisms have been produced, a growing number of non-model species are
      also being sequenced. In the absence of a reference, construction of a genome
      sequence necessitates de novo assembly which may be beyond the ability of many
      labs due to the large volumes of raw sequence data and extensive bioinformatics
      required. In contrast, the presence of a reference WGS allows for alignment which
      is more tractable than assembly. Recent work has highlighted that the reference
      need not come from the same species, potentially enabling a wide array of species
      WGS to be constructed using cross-species alignment. Here we report on the
      creation a draft WGS from a single bighorn sheep (Ovis canadensis) using
      alignment to the closely related domestic sheep (Ovis aries). RESULTS: Two
      sequencing libraries on SOLiD platforms yielded over 865 million reads, and
      combined alignment to the domestic sheep reference resulted in a nearly complete
      sequence (95% coverage of the reference) at an average of 12x read depth (104
      SD). From this we discovered over 15 million variants and annotated them relative
      to the domestic sheep reference. We then conducted an enrichment analysis of
      those SNPs showing fixed differences between the reference and sequenced
      individual and found significant differences in a number of gene ontology (GO)
      terms, including those associated with reproduction, muscle properties, and bone
      deposition. CONCLUSION: Our results demonstrate that cross-species alignment
      enables the creation of novel WGS for non-model organisms. The bighorn sheep WGS
      will provide a resource for future resequencing studies or comparative genomics.

PMID- 25990120
TI  - The international society for heart and lung transplantation working formulation
      for heart transplant rejection: Is it making the grade?
AB  - The cardinal criterion of a classification is utility. It provides one means in
      an attempt to give order to what would otherwise be a hopeless jumble of
      disconnected facts. As such it is of the first importance in any field of
      scholarly endeavor. 

PMID- 25990121
TI  - Parasitic diseases of the heart II: Toxoplasmosis and other protozoan and
      helminthic diseases.

PMID- 25990122
TI  - Porcine coronary artery organ culture: A model for the study of angioplasty
      injury.
AB  - The pathogenesis of coronary artery restenosis following angioplasty is not well
      understood. In order to carry out studies on the pathogenesis of restenosis, we
      developed and characterized an organ culture system using the porcine epicardial
      left anterior descending and circumflex coronary arteries. In nonangioplasty
      cultures at two weeks there was neointimal formation with intimal smooth muscle
      cells present within a loose matrix. All the neointimal cells beneath the
      endothelium stained positive for smooth muscle cell actin with alpha-SM1
      antibody. Smooth muscle cell proliferation was maximum between four and eight
      days. Angioplasty, carried out by local balloon inflation at the onset of
      culture, resulted in an augmentation of the neointimal thickness and a further
      increase in smooth muscle cell proliferation. Endothelial cells, however, were
      absent from the angioplasty site, having been damaged and lost at the time of
      angioplasty. Because there is a response to angioplasty in this organ culture
      model, it will be a useful way of studying many of the factors likely to be
      important in the regulation of restenosis following angioplasty. 

PMID- 25990123
TI  - Reperfusion injury in the ischemic myocardium.
AB  - Myocardial reperfusion injury is defined as the conversion of reversibly injured
      myocytes to irreversibly injured cells following temporary coronary artery
      occlusion. Although not universally accepted, the concept of lethal reperfusion
      injury is strongly supported by studies that temporally link an interventional
      therapy administered in the perireperfusion period to myocardial salvage.
      Myocardial reperfusion may be due to the deleterious consequences of cellular
      edema, calcium overload, free-radical generation, neutrophil infiltration, and
      microvascular damage. Current studies suggest that perfluorochemicals and
      adenosine (agents that preserve endothelium and attenuate neutrophil chemotaxis)
      are the most promising compounds that reduce infarct size in experimental animal
      models and may warrant clinical trials in man. 

PMID- 25990124
TI  - Ischemic myocardial injury in rapidly paced dogs: Contribution to ventricular
      dysfunction.
AB  - Chronic rapid ventricular pacing in the dog has been shown to provide a
      predictable and stable model of heart failure for which the operative
      pathomechanism remains in question. In a group of 20 dogs with congestive failure
      induced by rapid ventricular pacing for a mean duration of 29.5 +/- 13.1 days
      (range 7 to 55 days), mean left ventricular end diastolic pressure (LVEDP) was
      elevated as compared with unpaced controls (23.2 +/- 2.7 mmHg vs. 2.0 +/- 0 mmHg,
      p < 0.001). Gross myocardial hemorrhage was present at autopsy in 9 of 20 (45%)
      paced animals, and necrosis was present in 5 of 20 (25%). Histologic findings
      included acute ischemic myocardial injury with contraction band necrosis, wavy
      myofibers, and coagulation necrosis ranging from 0 to 4 lesions per paced animal
      (1.4 +/- 1.4, mean +/- SD), compared with none in unpaced animals (p < 0.03).
      Healed ischemic lesions ranged from 0 to 10 per animal (mean 3.2 +/- 2.9) versus
      none in control animals (p < 0.0001). Total injury score (acute plus healed) for
      each paced animal ranged from 0 to 12 (mean 4.6 +/- 2.9), compared with no injury
      in nonpaced controls (p < 0.0001). Thus ischemic injury reflected by multiple
      foci of acute and healed myocardial injury is a prominent and common feature in
      the canine rapid ventricular pacing model of heart failure. 

PMID- 25990125
TI  - Effects of cholesterol oxides on LDL receptors in cultured rabbit aortic smooth
      muscle cells.
AB  - The efficiency of receptor-mediated low-density lipoprotein (LDL) uptake and
      degradation has been implicated in the development of atherosclerosis. It has
      previously been shown that cholesterol oxides have more effect on the feedback
      control of cholesterol biosynthesis than does cholesterol per se on a molecule
      for-molecule basis. Cholesterol oxides may also modify the expression or function
      of the LDL receptors, resulting in alteration in cholesterol homeostasis. Rabbit
      aortic smooth muscle cells were preincubated in 5% lipoprotein-deficient medium
      for 24 hours and then incubated with 1 or 5 MUg/ml purified cholesterol or
      cholesterol oxides, including 25-hydroxycholesterol, 7-ketocholesterol,
      cholestane-3beta,5alpha,6beta-triol, and cholesterol 5alpha, 6alpha-epoxide for
      12 to 24 hours. The uptake of (125)I-LDL was significantly suppressed in a dose
      dependent fashion to 67% of the control value by 25-hydroxycholesterol at 1
      MUg/ml and to 53% at 5 MUg/ml after the 24-hour incubation period. Other
      cholesterol oxides also had inhibitory effects on the LDL uptake at 5 MUg/ml. At
      these concentrations cholesterol oxides additionally inhibited cellular
      degradation of LDL and the fractional turnover rate of LDL was prolonged. 

PMID- 25990126
TI  - Myocardial infarct size-Limiting effect of ischemic preconditioning: Its natural
      decay and the effect of repetitive preconditioning.
AB  - To characterize the cardioprotective effect of ischemic preconditioning, its
      natural decay and the effect of repetitive preconditioning were studied in the
      rabbit. Control rabbits underwent simple 30-minute coronary occlusion and 72 h
      reperfusion. In four groups, hearts were preconditioned with 5 minutes of
      ischemia and then allowed to "recover" for 5, 15, 25, or 35 minutes prior to the
      30-minute coronary occlusion. In another two groups of rabbits, the
      preconditioning (PC) was performed by two or four cycles of 5 minutes ischemia
      separated by 5 minutes reperfusion. Infarct size was 43.9% +/- 5.0% of area at
      risk in control rabbits. With recovery periods of 5 and 15 minutes, PC limited
      infarct size to 20.7% +/- 2.9% and 26.7% +/- 4.3% of the area at risk,
      respectively. As the recovery period increased, the infarct sizes progressively
      approached the control value, though PC still tended to be beneficial with a
      recovery time of 35 minutes. After two or four repetitions of 5-minute PC,
      infarct size was 16.4% +/- 4.2% and 13.7% +/- 2.6% of the area at risk,
      respectively, which were not significantly different from that after a single 5
      minute PC (20.7% +/- 2.9%). In another series of experiments, alteration of
      regional systolic thickening fraction (TF) after PC was assessed by an epicardial
      Doppler probe. Post-PC recovery of TF was 64.9% +/- 8.9% of baseline value at 5
      minutes and 73.2 +/- 7.2% at 35 minutes after reperfusion, showing the
      persistence of modest stunning. These results suggest that in the rabbit heart, 5
      minutes ischemia affords the myocardium a marked resistance against ischemic
      necrosis and that this resistance, which is unrelated to myocardial stunning,
      decays over a period of 30 minutes. Furthermore, the data imply that the
      resistance to ischemic injury is almost maximally induced by a single episode of
      5 minutes ischemia and is not markedly enhanced by its repetition. 

PMID- 25990127
TI  - Hypomagnesemia and isoproterenol cardiomyopathies: Protection by probucol.
AB  - Chronic magnesium deficiency is associated with injury of heart muscle, blood
      vessels, and neuronal tissue. Despite its clinical significance, the mechanism of
      magnesium deficiency-induced damage remains unclear. The myocardial necrosis
      induced by injecting catecholamines, which is augmented by magnesium deficiency,
      is thought to involve a free radical component through catecholamine
      autoxidation. alpha-tocopherol was shown to ameliorate the myocardial necrosis
      induced by magnesium-deficiency (Freedman et al. BBRC 1990;170:1102-1106),
      suggesting a role for free radicals in this process. If free-radical injury plays
      a role in magnesium deficiency, then the catecholamine-associated free-radical
      production may explain the synergistic myocardial injury between catecholamine
      and magnesium deficiency. To test the hypothesis that free-radical damage may
      play a role in magnesium deficiency-induced myocardial necrosis, we investigated
      the protective effects of probucol, a hypolipidemic agent with antioxidant
      properties. Hamsters were fed a Mg-deficient diet for 14 days with or without
      probucol. At the end of this period, some animals were sacrificed, while others
      were injected with isoproterenol and killed 48 hours later. All hearts were
      processed for morphometric analysis of the lesions. Changes in serum lipids were
      also determined. Probucol reduced the size and number of both the isoproterenol-
      and magnesium deficiency-induced cardiac lesions. Our results suggest that it is
      probucol's antioxidant property and not its hypolipidemic action that is
      responsible for this protection. 

PMID- 25990128
TI  - Fibroelastic papilloma: A not-so-benign cardiac tumor.
AB  - Six fibroelastic papillomas, ranging in size from 2 to 17 mm, were diagnosed
      among 106 benign cardiac tumors observed at our institute since 1970. Two were
      incidental autopsy findings, and involved the pulmonary and aortic semilunar
      valves, respectively; four were surgically removed specimens from the left side
      of the heart. Clinical diagnosis was achieved in two young subjects, aged 25 and
      31 years, by 2D-echo examination, following an episode of acute myocardial
      infarction precipitated during a soccer game; the tumor was related to the mitral
      valve apparatus in both cases, and a coronary embolism, either neoplastic or
      thrombotic, was the most likely cause of myocardial infarction. Thus, cardiac
      left-side fibroelastic papilloma should be considered a potentially
      lifethreatening tumor in hemodynamic terms. Like myxoma, this tumor entails the
      risk of systemic embolism that may also occur in the coronary arterial tree,
      precipitating myocardial infarction and sudden cardiac arrest. 

PMID- 25990129
TI  - Serum urate and obstructive sleep apnoea in severe obesity.
AB  - Obstructive sleep apnoea (OSA) may increase the risk of hyperuricaemia and
      predispose to gout. The evidence for the effects of OSA on serum urate in severe
      obesity is limited. This study investigated whether OSA was associated with serum
      urate in severe obesity and whether continuous positive airway pressure (CPAP)
      treatment was associated with a fall in urate. Severely obese subjects without
      known OSA or gout were recruited. Baseline assessments included urate, metabolic
      parameters, spirometry and overnight polysomnography. OSA patients were initially
      naive to treatment and were offered CPAP. At follow-up, change in urate was
      compared between CPAP-treated and non-CPAP-treated subjects. A high urate was
      defined as greater than the median. Logistic regression was performed to identify
      associations between (1) OSA and high urate at baseline and (2) use of CPAP and
      change in urate at follow-up. In total, 92 subjects were recruited (61 (66%) OSA
      and 31 (34%) non-OSA). Median urate was 345 MUmol/L. OSA was associated with high
      urate in females at baseline after adjusting for confounders (adjusted odds ratio
      ORadj = 10.2; 95% CI: 1.1, 93.5). At follow-up (14 months), 58 subjects (28 on
      CPAP and 30 not on CPAP) were reassessed. CPAP was significantly associated with
      a fall to a low urate category at follow-up ( = 0.017). Regression revealed a
      trend for a fall in urate category in the CPAP-treated group (ORadj = 9.3; 95%
      CI: 0.8, 97). Serum urate is associated with OSA in severely obese females and
      CPAP may reduce levels in patients with OSA. There may be a need to consider and
      assess for OSA in obese patients with hyperuricaemia and recurrent attacks of
      gout. 

PMID- 25990130
TI  - A psychological intervention for smoking cessation delivered as treatment for
      smokers with chronic obstructive pulmonary disease: Multiple needs of a complex
      group and recommendations for novel service development.
AB  - This pilot study investigated the benefits of adjunctive psychological
      intervention for smokers accessing standard smoking cessation interventions.
      Chronic obstructive pulmonary disease (COPD) smokers attending a smoking
      cessation service were offered up to 12 adjunctive clinical psychology sessions.
      Baseline data included demographics, smoking history, and disease severity.
      Outcomes included attendance and quit rate. In all, 59 patients with moderate
      COPD were referred. Of the 20 patients who attended training sessions, 7 (35%)
      were relapse prevention referrals and 13 (65%) were current smokers. Of the seven
      relapse prevention referrals, six (86%) maintained their quit, 2 of 13 (15%) of
      the current smoker group maintained a 28-day quit and 3 of 13 (23%) of current
      smokers reduced their tobacco intake. For COPD smokers with a heavy smoking
      history and multiple past quit attempts, there was insufficient evidence to show
      that additional psychological intervention leads to higher quit rates.
      Significant barriers to quitting and complex medical and psychosocial needs were
      identified in this group, suggesting that the current 'one-size-fits-all'
      approach to smoking cessation may not be sufficient to meet the needs of such a
      complex group. 

PMID- 25990131
TI  - Psychopathic personality development from ages 9 to 18: Genes and environment.
AB  - The genetic and environmental etiology of individual differences was examined in
      initial level and change in psychopathic personality from ages 9 to 18 years. A
      piecewise growth curve model, in which the first change score (G1) influenced all
      ages (9-10, 11-13, 14-15, and 16-18 years) and the second change score (G2) only
      influenced ages 14-15 and 16-18 years, fit the data better did than the standard
      single slope model, suggesting a turning point from childhood to adolescence. The
      results indicated that variations in levels and both change scores were mainly
      due to genetic (A) and nonshared environmental (E) influences (i.e., AE structure
      for G0, G1, and G2). No sex differences were found except on the mean values of
      level and change scores. Based on caregiver ratings, about 81% of variance in G0,
      89% of variance in G1, and 94% of variance in G2 were explained by genetic
      factors, whereas for youth self-reports, these three proportions were 94%, 71%,
      and 66%, respectively. The larger contribution of genetic variance and covariance
      in caregiver ratings than in youth self-reports may suggest that caregivers
      considered the changes in their children to be more similar as compared to how
      the children viewed themselves. 

PMID- 25990132
TI  - Endovascular Treatment of Occlusive Lesions in the Aortic Bifurcation with
      Kissing Polytetrafluoroethylene-Covered Stents.
AB  - PURPOSE: To determine the clinical outcomes of polytetrafluoroethylene covered
      balloon expandable stents (CBESs) in occlusive lesions of the aortic bifurcation
      in a kissing stent configuration. MATERIALS AND METHODS: The study included 69
      consecutive patients (29 men, 40 women) who underwent kissing stent procedures
      with CBESs between January 2003 and April 2009 in a single center. Patients who
      were previously treated with a CBES were excluded. Follow-up consisted of
      clinical investigation and duplex ultrasound examination. RESULTS: The primary
      patency was 88.1% at 1 year and 71.5% at 4 years, with secondary patency rates of
      88.1% and 75.3%, respectively. For patients receiving a stent for the first time,
      primary patency was 91.3% at 1 year and 77.1% at 4 years. For patients who had
      received previous stents, patency was 83.6% at 1 year and 65.2% at 4 years (P =
      .83). There were no differences in secondary patency and freedom from target
      lesion reintervention (TLR). Loss of primary patency was mainly caused by stent
      occlusions (14 cases [78%]). The freedom from TLR at 4 years was 76.8%.
      CONCLUSIONS: Patency rates and freedom from TLR of CBESs in the kissing stent
      configuration with up to 4 years of follow-up were satisfying and mainly affected
      by stent occlusions. Studies focusing on optimizing stent configuration and
      medical care to reduce the incidence of thrombosis are indicated to improve
      results further.

PMID- 25990133
TI  - Long-Term Patency and Clinical Analysis of Expanded Polytetrafluoroethylene
      Covered Transjugular Intrahepatic Portosystemic Shunt Stent Grafts.
AB  - PURPOSE: To evaluate long-term patency and symptomatic recurrence rates following
      transjugular intrahepatic portosystemic shunt (TIPS) creation with expanded
      polytetrafluoroethylene (ePTFE)-covered stent grafts and to determine the
      necessity of extended clinical follow-up beyond 2 years after TIPS creation.
      MATERIALS AND METHODS: A retrospective review including 262 TIPSs created with
      ePTFE-covered stent grafts between July 2002 and October 2012 was performed.
      Primary, primary assisted, and secondary patency rates were calculated.
      Assessment of clinical data included technical, hemodynamic, and clinical success
      rates, as well as mortality after TIPS creation. RESULTS: Primary patency rates
      at 2, 4, and 6 years were 74%, 62%, and 50%, respectively. Primary assisted
      patency rates at 2, 4, and 6 years were 93%, 85%, and 78%, respectively.
      Secondary patency rates at 2, 4, and 6 years were 99%, 91%, and 84%,
      respectively. Technical and hemodynamic success rates were 99% and 93%,
      respectively. Clinical success rates for refractory ascites were 66% (complete
      response) and 90% (partial response); clinical success rate for bleeding/varices
      was 90%. Mortality rates at 2, 4, and 6 years after TIPS creation were 27%, 38%,
      and 46%, respectively. At the median wait time until transplantation, patients
      had an 84% chance of being alive. TIPS dysfunction developed in 21% of patients;
      30% of revisions occurred later than 2 years during follow-up. CONCLUSIONS:
      Beyond 2 years after TIPS creation, patency rates gradually decrease, mortality
      rates continue to increase, and the chance of recurrent ascites or bleeding
      remains present. Together, these findings suggest that continued clinical follow
      up beyond 2 years is necessary in patients with a TIPS created with an ePTFE
      covered stent graft.

PMID- 25990134
TI  - Proximal Splenic Artery Embolization in Chemotherapy-Induced Thrombocytopenia: A
      Retrospective Analysis of 13 Patients.
AB  - PURPOSE: To determine if proximal splenic artery embolization (PSAE) provides a
      safe and effective alternative to alleviate chemotherapy-induced thrombocytopenia
      (CIT), allowing patients with cancer to resume chemotherapy regimens. MATERIALS
      AND METHODS: Thirteen patients (9 men, 4 women; mean age, 63 y) with underlying
      malignancy (pancreatic adenocarcinoma, n = 6; cholangiocarcinoma, n = 5; other, n
      = 2) complicated by CIT underwent PSAE. Mean platelet counts were calculated
      before the initiation of chemotherapy, at the nadir that resulted in
      discontinuation of chemotherapy before the PSAE procedure, at peak values after
      the procedure, and at a mean follow-up of 9.2 months. The time to reinitiation of
      chemotherapy after PSAE was calculated. RESULTS: Baseline platelet count before
      initiation of chemotherapy was 162 * 10(9)/L (range, 90-272 * 10(9)/L). The
      platelet count nadir resulting in cessation of chemotherapy was 45 * 10(9)/L
      (range, 23-67 * 10(9)/L), and the pre-PSAE platelet count was 88 * 10(9)/L
      (range, 49-131 * 10(9)/L). The post-PSAE peak platelet count improved
      significantly (to 209 * 10(9)/L; range, 83-363 * 10(9)/L) compared with the nadir
      counts and the pre-PSAE counts (P < .01) at a mean short-term follow-up of 35
      days (range, 7-91 d). The counts at follow-up to 9.2 months (range, 3-15 mo) were
      152 * 10(9)/L (range, 91-241 * 10(9)/L). All patients became eligible to resume
      chemotherapy. The time to initiation of chemotherapy after PSAE averaged 22 days
      (range, 4-58 d) in 12 patients; one patient declined chemotherapy. CONCLUSIONS:
      Proximal splenic artery embolization appears to be safe and effective in
      alleviating CIT, allowing resumption of systemic chemotherapy. Further studies
      may help guide patient selection by identifying characteristics that allow a
      sustained improvement in thrombocytopenia.

PMID- 25990135
TI  - Effect of Molecular Stacking on Exciton Diffusion in Crystalline Organic
      Semiconductors.
AB  - Exciton diffusion is at the heart of most organic optoelectronic devices'
      operation, and it is currently the most limiting factor to their achieving high
      efficiency. It is deeply related to molecular organization, as it depends on
      intermolecular distances and orbital overlap. However, there is no clear
      guideline for how to improve exciton diffusion with regard to molecular design
      and structure. Here, we use single-crystal charge-transfer interfaces to probe
      favorable exciton diffusion. Photoresponse measurements on interfaces between
      perylenediimides and rubrene show a higher photocurrent yield (+50%) and extended
      spectral coverage (+100 nm) when there is increased dimensionality of the
      percolation network and stronger orbital overlap. This is achieved by very short
      interstack distances in different directional axes, which favors exciton
      diffusion by a Dexter mechanism. Even if the core of the molecule shows strong
      deviation from planarity, the similar electrical resistance of the different
      systems, planar and nonplanar, shows that electronic transport is not
      compromised. These results highlight the impact of molecular organization in
      device performance and the necessity of optimizing it to take full advantage of
      the materials' properties. 

PMID- 25990136
TI  - A Systematic Review of Histone Lysine-Specific Demethylase 1 and Its Inhibitors.
AB  - Histone lysine-specific demethylase 1 (LSD1) is the first discovered and reported
      histone demethylase by Dr. Shi Yang's group in 2004. It is classified as a member
      of amine oxidase superfamily, the common feature of which is using the flavin
      adenine dinucleotide (FAD) as its cofactor. Since it is located in cell nucleus
      and acts as a histone methylation eraser, LSD1 specifically removes mono- or
      dimethylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through
      formaldehyde-generating oxidation. It has been indicated that LSD1 and its
      downstream targets are involved in a wide range of biological courses, including
      embryonic development and tumor-cell growth and metastasis. LSD1 has been
      reported to be overexpressed in variety of tumors. Inactivating LSD1 or
      downregulating its expression inhibits cancer-cell development. LSD1 targeting
      inhibitors may represent a new insight in anticancer drug discovery. This review
      summarizes recent studies about LSD1 and mainly focuses on the basic
      physiological function of LSD1 and its involved mechanisms in pathophysiologic
      conditions, as well as the development of LSD1 inhibitors as potential anticancer
      therapeutic agents. 

PMID- 25990138
TI  - Slash unsocial hours pay at your peril, minister.

PMID- 25990139
TI  - Chief nursing officer says we need to stop talking about poor image.

PMID- 25990137
TI  - Patient Preferences and Surrogate Decision Making in Neuroscience Intensive Care
      Units.
AB  - In the neuroscience intensive care unit (NICU), most patients lack the capacity
      to make their own preferences known. This fact leads to situations where
      surrogate decision makers must fill the role of the patient in terms of making
      preference-based treatment decisions, oftentimes in challenging situations where
      prognosis is uncertain. The neurointensivist has a large responsibility and role
      to play in this shared decision-making process. This review covers how NICU
      patient preferences are determined through existing advance care documentation or
      surrogate decision makers and how the optimum roles of the physician and
      surrogate decision maker are addressed. We outline the process of reaching a
      shared decision between family and care team and describe a practice for
      conducting optimum family meetings based on studies of ICU families in crisis. We
      review challenges in the decision-making process between surrogate decision
      makers and medical teams in neurocritical care settings, as well as methods to
      ameliorate conflicts. Ultimately, the goal of shared decision making is to
      increase knowledge amongst surrogates and care providers, decrease decisional
      conflict, promote realistic expectations and preference-centered treatment
      strategies, and lift the emotional burden on families of neurocritical care
      patients. 

PMID- 25990140
TI  - Welsh assembly committee backs law on safe staffing in hospitals.

PMID- 25990141
TI  - Attack unsocial hours pay at your peril, RCN warns.

PMID- 25990142
TI  - Mary Seacole statue progress stalls as appeal chair says funds are drying up.

PMID- 25990143
TI  - 'My work in Africa made me aware of wasted resources'.

PMID- 25990144
TI  - Jobs figures point to dilution of skills in emergency departments.

PMID- 25990145
TI  - O'Grady pays tribute to our winners.

PMID- 25990146
TI  - Hand grip strength linked to stroke and heart failure risk.

PMID- 25990147
TI  - Care quality system promises time benefits.

PMID- 25990149
TI  - New scheme could punish regular absenteeism with financial penalty.

PMID- 25990150
TI  - First minister praises front line staff.

PMID- 25990151
TI  - Tories prepare to push ahead with 24/7 integrated community care.

PMID- 25990157
TI  - Autism spectrum disorder.

PMID- 25990159
TI  - When you need to have a quiet word.

PMID- 25990158
TI  - New Code punishes failure to speak out.

PMID- 25990168
TI  - Dying Matters.

PMID- 25990170
TI  - MyFitnessPal.

PMID- 25990172
TI  - Omitting spirituality from NMC code disadvantages our patients.

PMID- 25990174
TI  - Information systems are too vital to be left to non-nursing geeks.

PMID- 25990173
TI  - Take politics out of the NHS and show us it is a true priority.

PMID- 25990176
TI  - Selfless Ebola nurses deserve to have their own special award.

PMID- 25990177
TI  - It's time to stop equating the spiritual with the religious.

PMID- 25990178
TI  - Heed the evidence on place of spiritual needs in health care.

PMID- 25990180
TI  - Using narrative in nursing research.
AB  - Narrative is a term used in everyday life. While it refers to a spoken or written
      account or story, it is also an increasingly popular research method. This
      article explores the role of narrative in nursing research and practice, and
      evaluates the use of narrative as a research method. Narrative is the study of
      how humans experience the world and how they interpret this experience. It can be
      an excellent research method to expand understanding of healthcare provision and
      individual patient experience. 

PMID- 25990181
TI  - Preventing infection in rehabilitation centres.
AB  - Recent military conflicts have provided new challenges for Defence Medical
      Services, and the specialty of infection prevention and control has not been
      exempt from these. The mechanisms of injury and the harsh environments in which
      military injuries are sustained have resulted in unusual infections with multiple
      resistance to antimicrobial agents. Although the multidisciplinary team faces
      many issues in the acute phase of the patient's rehabilitation, it is the
      continued infection risk to patients that is the biggest challenge for both the
      infection prevention and control team and the wider multidisciplinary team.
      Rehabilitation centres may evoke an image of healthy individuals who require
      little nursing care but, for those attending the Defence Medical Rehabilitation
      Centre, this is not always so and staff are often challenged by continuing
      infection problems. There is also a risk of patients developing new infections as
      a result of unhealed wounds and the use of invasive devices, such as indwelling
      catheters, which are essential if patients are to maintain their everyday
      activities. 

PMID- 25990182
TI  - Improving surgical outcomes for people with dementia.
AB  - Surgical intervention in older people with dementia is becoming increasingly
      common as the population ages and the number of people with dementia continues to
      rise. People with dementia have unique needs that require sensitive management at
      all stages of hospitalisation for surgery. This article sets out a suggested
      pathway for the care of these patients, in the form of a flow chart. It discusses
      recognition and assessment of dementia and delirium, issues of capacity and
      consent, interventions required for optimum care of older people with dementia
      and peri-operative management. It explores the role of family and friends in
      achieving integrated care. 

PMID- 25990183
TI  - Subcutaneous injection.

PMID- 25990184
TI  - Shaping better community care.

PMID- 25990185
TI  - Guaranteed to make you smile.

PMID- 25990187
TI  - Quality people = quality care.

PMID- 25990188
TI  - Front line preparation.

PMID- 25990189
TI  - Establishing a Common Metric for Physical Function: Linking the HAQ-DI and SF-36
      PF Subscale to PROMIS((r)) Physical Function.
AB  - BACKGROUND: Physical function (PF) is a common health concept measured in
      clinical trials and clinical care. It is measured with different instruments that
      are not directly comparable, making comparative effectiveness research (CER)
      challenging when PF is the outcome of interest. OBJECTIVE: Our goal was to
      establish a common reporting metric, so that scores on commonly used physical
      function measures can be converted into PROMIS scores. DESIGN: Following a single
      sample linking design, all participants completed items from the NIH Patient
      Reported Outcomes Measurement Information System (PROMIS(r)) Physical Function
      (PROMIS PF) item bank and at least one other commonly used "legacy" measure: the
      Health Assessment Questionnaire (HAQ) or the Short Form-36 physical function ten
      item PF scale (SF-36 PF). A common metric was created using analyses based on
      item response theory (IRT), producing score cross-walk tables. PARTICIPANTS:
      Participants (N = 733) were part of an internet panel, many of whom reported one
      or more chronic health conditions. MAIN MEASURES: PROMIS PF, SF-36 PF, and the
      HAQ-Disability Index (HAQ-DI). RESULTS: Our results supported the hypothesis that
      all three scales measure essentially the same concept. Cross-walk tables for use
      in CER are therefore justified. CONCLUSIONS: HAQ-DI and SF-36 PF results can be
      expressed on the PROMIS PF metric for the purposes of CER and other efforts to
      compare PF results across studies that utilize any one of these three measures.
      Clinicians seeking to incorporate PROs into their clinics can collect patient
      data on any one of these three instruments and estimate the equivalent on the
      other two.

PMID- 25990190
TI  - Impact of an Overnight Internal Medicine Academic Hospitalist Program on Patient
      Outcomes.
AB  - BACKGROUND: Many academic hospitals have implemented overnight hospitalists to
      supervise house staff and improve outcomes, but few studies have described the
      impact of this role. OBJECTIVE: To investigate the effect of an overnight
      academic hospitalist program on patient-level outcomes. Secondary objectives were
      to describe the program's revenue generation and work tasks. DESIGN:
      Retrospective interrupted time-series analysis of patients admitted to the
      medicine service before and after implementation of the program. PARTICIPANTS:
      All patients aged 18 and older admitted to the acute or intermediate care units
      between 7:00 p.m. and 6:59 a.m. during the period before (April 2011-August 2012)
      and after (September 2012-April 2014) program implementation. INTERVENTION: An on
      site attending-level physician directly supervising medicine house staff
      overnight, providing clinical care during high-volume periods, and ensuring safe
      handoffs to daytime providers. MAIN MEASURES: Primary outcomes included in
      hospital mortality, 30-day hospital readmissions, length of stay, and upgrades in
      care on the night of admission and during hospitalization. Multivariable models
      estimated the effect on outcomes after adjusting for secular trends. Revenue
      generation and work tasks are reported descriptively. KEY RESULTS: During the
      study period, 6484 patients were admitted to the medicine service: 2722 (42 %)
      before and 3762 (58 %) after implementation. No differences were found in
      mortality (1.1 % vs. 0.9 %, p=0.38), 30-day readmissions (14.8 % vs. 15.6 %,
      p=0.39), mean length of stay (3.09 vs. 3.08 days, p=0.86), or upgrades to
      intensive care on the night of admission (0.4 % vs. 0.7 %, p=0.11) or during
      hospitalization (3.5 % vs. 4.2 %, p=0.20). During the first year, hospitalists
      billed 1209 patient encounters (3.3/shift) and 63 procedures (0.2/shift), and
      supervised 1939 patient admissions (6.12/shift) while supervising house staff 3
      h/shifts. CONCLUSIONS: Implementation of an overnight academic hospitalist
      program showed no impact on several important clinical outcomes, and revenue
      generation was modest. As overnight hospitalist programs develop, investigations
      are needed to delineate the return on investment and focus on other outcomes that
      may be more sensitive to change, such as errors and provider/patient
      satisfaction.

PMID- 25990191
TI  - Healthcare Expenditures Associated with Depression Among Individuals with
      Osteoarthritis: Post-Regression Linear Decomposition Approach.
AB  - BACKGROUND: Depression is common among individuals with osteoarthritis and leads
      to increased healthcare burden. The objective of this study was to examine excess
      total healthcare expenditures associated with depression among individuals with
      osteoarthritis in the US. DESIGN: Adults with self-reported osteoarthritis (n =
      1881) were identified using data from the 2010 Medical Expenditure Panel Survey
      (MEPS). Among those with osteoarthritis, chi-square tests and ordinary least
      square regressions (OLS) were used to examine differences in healthcare
      expenditures between those with and without depression. Post-regression linear
      decomposition technique was used to estimate the relative contribution of
      different constructs of the Anderson's behavioral model, i.e., predisposing,
      enabling, need, personal healthcare practices, and external environment factors,
      to the excess expenditures associated with depression among individuals with
      osteoarthritis. All analysis accounted for the complex survey design of MEPS. KEY
      RESULTS: Depression coexisted among 20.6 % of adults with osteoarthritis. The
      average total healthcare expenditures were $13,684 among adults with depression
      compared to $9284 among those without depression. Multivariable OLS regression
      revealed that adults with depression had 38.8 % higher healthcare expenditures (p
      < 0.001) compared to those without depression. Post-regression linear
      decomposition analysis indicated that 50 % of differences in expenditures among
      adults with and without depression can be explained by differences in need
      factors. CONCLUSIONS: Among individuals with coexisting osteoarthritis and
      depression, excess healthcare expenditures associated with depression were mainly
      due to comorbid anxiety, chronic conditions and poor health status. These
      expenditures may potentially be reduced by providing timely intervention for need
      factors or by providing care under a collaborative care model.

PMID- 25990192
TI  - Gene network analysis of Arabidopsis thaliana flower development through dynamic
      gene perturbations.
AB  - Understanding how flowers develop from undifferentiated stem cells has occupied
      developmental biologists for decades. Key to unraveling this process is a
      detailed knowledge of the global regulatory hierarchies that control
      developmental transitions, cell differentiation and organ growth. These
      hierarchies may be deduced from gene perturbation experiments, which determine
      the effects on gene expression after specific disruption of a regulatory gene.
      Here, we tested experimental strategies for gene perturbation experiments during
      Arabidopsis thaliana flower development. We used artificial miRNAs (amiRNAs) to
      disrupt the functions of key floral regulators, and expressed them under the
      control of various inducible promoter systems that are widely used in the plant
      research community. To be able to perform genome-wide experiments with stage
      specific resolution using the various inducible promoter systems for gene
      perturbation experiments, we also generated a series of floral induction systems
      that allow collection of hundreds of synchronized floral buds from a single
      plant. Based on our results, we propose strategies for performing dynamic gene
      perturbation experiments in flowers, and outline how they may be combined with
      versions of the floral induction system to dissect the gene regulatory network
      underlying flower development. 

PMID- 25990193
TI  - Use of tracheal stenting in the palliation of anaplastic thyroid carcinoma:
      tertiary centre experience.
AB  - BACKGROUND: Anaplastic thyroid carcinoma is rare but carries a poor prognosis.
      Anaplastic thyroid carcinoma leads to tracheal compression, airway compromise and
      eventually death. Airway compromise, a particularly distressing symptom, can be
      palliated with tracheal stenting. METHOD: A retrospective case note analysis was
      conducted of patients diagnosed with anaplastic thyroid carcinoma between July
      2003 and July 2013. RESULTS: Twelve patients with anaplastic thyroid carcinoma
      were identified. Four patients underwent palliative tracheal stenting. Three
      patients had no dyspnoea at the time of stenting. Two stented patients
      subsequently developed dyspnoea secondary to stent migration; this was managed
      successfully with stent exchange. The other stented patient remained asymptomatic
      with regards to dyspnoea. All non-stented patients died with or from airway
      compromise. CONCLUSION: Tracheal stenting is a relatively safe and effective
      method for palliation of distressing airway symptoms in patients with anaplastic
      thyroid carcinoma. Early prophylactic tracheal stenting in anaplastic thyroid
      carcinoma may be an effective option to prevent development of airway compromise
      as the disease progresses.

PMID- 25990194
TI  - Vibrationally Coherent Preparation of the Transition State for Photoisomerization
      of the Cyanine Dye Cy5 in Water.
AB  - Femtosecond pump-continuum probe spectroscopy with impulsive excitation was
      employed to observe coherent wavepacket motions of the cyanine dye Cy5 in water
      that promote photoisomerization after optical preparation of the first excited
      singlet state, S1. The chief component in the excited-state vibrational coherence
      is a resonance Raman-inactive, 273 cm(-1) mode of mixed carbon-carbon bond length
      alternation and out-of-plane or twisting character. The ultrafast (30 fs) damping
      of these motions arises from trajectories that irreversibly cross the transition
      state barrier; after several recurrences to the transition state region,
      vibrational cooling traps a significant fraction of the excited-state molecules
      in the planar, Franck-Condon region of the potential energy surface. Motion in
      the 273 cm(-1) promoting mode is apparently launched by a change in conformation
      of the conjugated polyene backbone during the first few vibrations of the high
      frequency C-C and C?C bond length alternation coordinates that principally
      contribute to the initial displacement from the Franck-Condon structure. To our
      knowledge, this work provides the first direct observations of the intramolecular
      redistribution of excited-state potential energy into reactive motions that are
      rapidly damped by transition state barrier-crossing events leading to
      photoisomerization in a conjugated polyene. These results provide insight into
      the vibrational dynamics that contribute to the photoisomerization of retinal
      protonated Schiff bases in the rhodopsins and to the formation of intramolecular
      charge transfer character in carotenoids in photosynthetic light-harvesting
      proteins. 

PMID- 25990195
TI  - Self-reported hand hygiene practices, and feasibility and acceptability of
      alcohol-based hand rubs among village healthcare workers in Inner Mongolia,
      China.
AB  - BACKGROUND: Good hand hygiene is critical to reduce the risk of healthcare
      associated infections. Limited data are available on hand hygiene practices from
      rural healthcare systems in China. AIM: To assess the feasibility and
      acceptability of sanitizing hands with alcohol-based hand rubs (ABHRs) among
      Chinese village healthcare workers, and to assess their hand hygiene practice.
      METHODS: Five hundred bottles of ABHR were given to village healthcare workers in
      Inner Mongolia, China. Standardized questionnaires collected information on their
      work load, availability, and usage of hand hygiene facilities, and knowledge,
      attitudes, and practices of hand hygiene. FINDINGS: In all, 369 (64.2%)
      participants completed the questionnaire. Although 84.5% of the ABHR recipients
      believed that receiving the ABHR improved their hand hygiene practice, 78.8% of
      recipients would pay no more than US$1.5 out of their own pocket (actual cost
      US$4). The majority (77.2%) who provided medical care at patients' homes never
      carried hand rubs with them outside their clinics. In general, self-reported hand
      hygiene compliance was suboptimal, and the lowest compliance was 'before touching
      a patient'. Reported top three complaints with using ABHR were skin irritation,
      splashing, and unpleasant residual. Village doctors with less experience
      practised less hand hygiene. CONCLUSION: The overall acceptance of ABHR among the
      village healthcare workers is high as long as it is provided to them for free/low
      cost, but their overall hand hygiene practice is suboptimal. Hand hygiene
      education and training is needed in settings outside of traditional healthcare
      facilities.

PMID- 25990197
TI  - Co-electrodeposition of RuO2-MnO2 nanowires and the contribution of RuO2 to the
      capacitance increase.
AB  - A wide range of metal oxides have been studied as pseudocapitors, with the goal
      of achieving higher power than traditional batteries and higher energy than
      traditional capacitors. However, most metal oxides have relatively low
      conductivity, and the few exceptions, like RuO2, are prohibitively expensive.
      Mixed metal oxides provided an opportunity to incorporate small amounts of
      expensive materials to enhance the performance of a less expensive, poorer
      performing material. Here, by homogeneously co-depositing a small amount of
      energy dense and conductive RuO2 into MnO2 nanowires, we demonstrate an
      improvement in specific capacitance. Importantly, we also demonstrate that this
      improvement is not primarily provided by redox activity of RuO2, but rather by
      improvement of the composite conductivity. A series of RuO2-MnO2 composite
      nanowires with different RuO2 loading percentages have been synthesized by
      performing co-electrodeposition in a porous alumina template. The structure of
      these RuO2-MnO2 nanowires is characterized by TEM and SEM. EDS mapping shows that
      RuO2 is well distributed in MnO2 matrix nanowires. The chemical constituents and
      the phase of these composite nanowires are confirmed by X-ray photoelectron and
      Raman spectroscopy. The amount of RuO2 is controlled by varying the
      concentrations of RuCl3 and MnAc2 in the deposition solution. The precise masses
      of MnO2 and RuO2 are determined by ICP-AES elemental analysis. MnO2 nanowires
      with 6.70 wt% RuO2 demonstrate a specific capacitance of 302 F g(-1) at 20 mV s(
      1), compared to 210 F g(-1) for pristine MnO2 nanowires. Investigation of the
      RuO2 loading amount effect was conducted by electrochemical impedance
      spectroscopy (EIS) and deconvolution of capacitances, using methods previously
      reported by both Dunn and Transsiti. The RuO2-MnO2 nanowires studied here
      demonstrate a simple, straighforward method to overcome the intrinsically poor
      conductivity of MnO2, and clarify the source of RuO2's contribution to the
      improved performance. 

PMID- 25990196
TI  - Effects of focal muscle vibration on physical functioning in patients with knee
      osteoarthritis: a randomized controlled trial.
AB  - BACKGROUND: Knee osteoarthritis (OA) is a chronic condition characterized by
      pain, stiffness and functional limitations. According to the OsteoArthritis
      Research Society International (OARSI) recommendations, patients with knee OA
      should undertake regular quadriceps muscle strengthening exercises. Whole body
      vibration (WBV) proved its effectiveness in strengthening of the quadriceps
      muscles and improving balance in chronic knee OA patients. To date, there are no
      published studies that investigated the effects of focal muscle vibration (FMV)
      in these patients. AIM: The aim of the present study was to evaluate the effects
      of FMV on physical functioning in patients with symptomatic knee OA. DESIGN:
      Randomized controlled trial. SETTING: Outpatient clinic, University Hospital.
      POPULATION: Men and women aged 60 years or older with radiographic diagnosis of
      mild to moderate monolateral knee OA (Kellgren-Lawrence grade II or III) and
      chronic knee pain. METHODS: Patients were randomized in two groups (treatment
      group and placebo control group). The treatment group received FMV treatment,
      according to the "repeated muscle vibration" protocol. The control group received
      a sham treatment. The primary outcome measure was the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures
      were the Short Physical Performance Battery (SPPB) and the Performance-Oriented
      Mobility Assessment (POMA). Follow up evaluations were done at 3 and 6 months.
      RESULTS: Fifty patients were recruited and randomly assigned to either the study
      or control group. There was a statistical significant difference between the two
      groups both for primary (WOMAC) and secondary (SPPB and POMA) outcomes.
      CONCLUSIONS: In this study, FMV therapy has proven to be effective and safe in
      improving functioning of patients affected by mild to moderate chronic knee OA.
      CLINICAL REHABILITATION IMPACT: The use of FMV therapy might be an additional and
      safe tool in the conservative management of knee OA.

PMID- 25990198
TI  - Direct Pulp Capping with Calcium Hydroxide or Mineral Trioxide Aggregate: A Meta
      analysis.
AB  - INTRODUCTION: The purpose of this study was to compare the effectiveness of
      mineral trioxide aggregate (MTA) and calcium hydroxide (CH) as pulp capping
      materials in humans by means of a meta-analysis. METHODS: The PubMed, Cochrane
      Library, Embase, and Web of Knowledge databases were used in the literature
      search from their establishment date until December 7, 2014. Studies that met the
      inclusion criteria were accepted, and necessary information was extracted by 2
      authors independently using a standardized form. The success rate, inflammatory
      response, and dentin bridge formation were evaluated. RESULTS: Thirteen studies
      met the inclusion criteria. There was no significant heterogeneity between
      studies, so a fixed-effects model was used. The MTA treatment groups showed a
      significantly higher success rate compared with CH-capped groups (randomized
      controlled trials: odds ratio [OR] = 2.26; 95% confidence interval [CI] = 1.33
      3.85; P = .003; retrospective nonrandomized trials: OR = 2.88; 95% CI, 1.86-4.44;
      P < .00001). MTA was superior to CH in terms of the absence of an inflammatory
      response as well as dentin bridge formation, with the OR being 4.56 (95% CI, 2.65
      7.83) and 3.56 (95% CI, 1.89-6.70), respectively. CONCLUSIONS: MTA has a higher
      success rate and results in less pulpal inflammatory response and more
      predictable hard dentin bridge formation than CH. MTA appears to be a suitable
      replacement of CH used for direct pulp capping.

PMID- 25990199
TI  - Cathepsin K Inhibitor Regulates Inflammation and Bone Destruction in
      Experimentally Induced Rat Periapical Lesions.
AB  - INTRODUCTION: Cathepsin K is highly expressed in osteoclasts and plays an
      essential role in bone resorption. NC-2300 is an artificially designed cathepsin
      K inhibitor, and its application to experimentally induced arthritis induces down
      regulation of bone destruction. In this study, we evaluated the effects of NC
      2300 on inflammation and bone destruction in experimentally induced rat
      periapical lesions. METHODS: The dental pulps of lower first molars in rats were
      extirpated, and the pulp chambers were left open to the oral environment. NC-2300
      and phosphate-buffered saline were administered orally twice a day in the
      experimental and control groups, respectively. Animals were sacrificed on day 21,
      and the mandibles were extracted. The left hemimandibles were used for micro
      computed tomographic and histologic examination. For the right hemimandibles, RNA
      was extracted from the periapical tissues surrounding the root apices, and
      inflammatory mediator expression was examined by real-time polymerase chain
      reaction using complementary DNA converted from extracted RNA. RESULTS: The size
      of the periapical lesion, number of tartrate-resistant acid phosphatase-positive
      osteoclasts and major histocompatibility complex class II molecule-expressing
      macrophages in the experimental group decreased significantly when compared with
      the control group. The expression of proinflammatory cytokines in the
      experimental group was significantly suppressed when compared with the control
      group. CONCLUSIONS: These results suggest that the cathepsin K inhibitor may
      inhibit not only cathepsin K activity in osteoclasts but also inflammatory
      mediator synthesis relating to osteoclastogenesis, and these synergistic effects
      may be involved in the suppression of periapical lesion expansion.

PMID- 25990200
TI  - Quantitative dynamic imaging of immune cell signalling using lentiviral gene
      transfer.
AB  - Live-cell imaging of fluorescent fusion proteins has transformed our
      understanding of mammalian cell signalling and function. However, some cellular
      systems such as immune cells are unsuitable or refractory to many existing
      transgene delivery methods thus limiting systematic analyses. Here, a flexible
      lentiviral gene transfer platform for dynamic time-lapse imaging has been
      developed and validated with single-molecule spectroscopy, mathematical modelling
      and transcriptomics and used for analysis of a set of inflammation-related
      signalling networks. Time-lapse imaging of nuclear factor kappa B (NF-kappaB),
      signal transducer and activator of transcription (STATs) and nuclear factor of
      activated T-cells (NFAT) in mammalian immune cell lines provided evidence for
      heterogeneous temporal encoding of inflammatory signals. In particular, the
      absolute quantification of single-cell responses over time via fluorescent
      correlation spectroscopy (FCS) showed that NF-kappaB p65 activation in response
      to tumour necrosis factor alpha (TNFalpha) was differentially encoded in variable
      amplitude of nuclear translocation between immune and non-immune cells. The
      absolute number of activated molecules was dictated in part by the cell size,
      suggesting a morphology-dependent regulatory mechanism. The developed platform
      will enable further absolute quantitative analyses of the dynamic interactions
      between signalling networks, in and between individual cells, allowing better
      integration with mathematical models of signalling networks. 

PMID- 25990201
TI  - Queen's University Emergency Medicine Simulation OSCE: an Advance in Competency
      Based Assessment.

PMID- 25990202
TI  - Consumption of fruits and vegetables and probabilistic assessment of the
      cumulative acute exposure to organophosphorus and carbamate pesticides of
      schoolchildren in Slovenia.
AB  - OBJECTIVE: Adequate consumption of fruits and vegetables is a part of
      recommendations for a healthy diet. The aim of the present study was to assess
      acute cumulative dietary exposure to organophosphorus and carbamate pesticides
      via fruit and vegetable consumption by the population of schoolchildren aged 11
      12 years and the level of risk for their health. DESIGN: Cumulative probabilistic
      risk assessment methodology with the index compound approach was applied.
      SETTING: Slovenia, primary schools. SUBJECTS: Schoolchildren (n 1145) from thirty
      one primary schools in Slovenia. Children were part of the PRO GREENS study
      2009/10 which assessed 11-year-olds' consumption of fruit and vegetables in ten
      European countries. RESULTS: The cumulative acute exposure amounted to 8.3 (95%
      CI 7.7, 10.6) % of the acute reference dose (ARfD) for acephate as index compound
      (100 ug/kg body weight per d) at the 99.9th percentile for daily intake and to
      4.5 (95% CI 3.5, 4.7) % of the ARfD at the 99.9th percentile for intakes during
      school time and at lunch. Apples, bananas, oranges and lettuce contributed most
      to the total acute pesticides intake. CONCLUSIONS: The estimations showed that
      acute dietary exposure to organophosphorus and carbamate pesticides is not a
      health concern for schoolchildren with the assessed dietary patterns of fruit and
      vegetable consumption.

PMID- 25990204
TI  - Martius labial fat pad procedure: technique and long-term outcomes.

PMID- 25990203
TI  - Medium-term and long-term outcomes following placement of midurethral slings for
      stress urinary incontinence: a systematic review and metaanalysis.
AB  - INTRODUCTION AND HYPOTHESIS: Questions regarding the long-term efficacy and
      safety of midurethral slings (MUS) are still unresolved, notwithstanding the
      widespread use of these procedures. The objective of this review was to evaluate
      the long-term outcomes of retropubic MUS (RP-MUS) procedures and the medium-term
      outcomes of transobturator MUS (TO-MUS) procedures. METHODS: MEDLINE, EMBASE,
      NLH, ClinicalTrials.gov, and Google Scholar databases were searched up to June
      2014 with restriction to English language and using the search terms: "stress
      urinary incontinence", "midurethral sling", "tension-free tape", "transobturator
      tape", and "follow-up". Studies with a follow-up of 36 months for TO-MUS and 60
      months for RP-MUS were searched. Only studies comparing a RP-MUS or TO-MUS with
      another synthetic sling were included. Data from 49 studies were included. Data
      were expressed as odds ratios (OR) with 95 % confidence intervals (CI) and
      combined using the Mantel-Haenszel fixed effects model. Differences in the
      proportions were evaluated using the chi-squared test. RESULTS: RP-MUS had
      similar objective cure rates (OR 1.15, 95 % CI 0.75 - 1.76) but higher subjective
      cure rates than TO-MUS (OR 1.76, 95 % CI 1.08 - 2.86). No differences were
      observed between outside-in (TOT) and inside-out (TVT-O) and between TO-MUS and
      minisling. Bladder injuries were more frequent (OR 7.01, 95 % CI 2.94 - 17.90)
      and vaginal erosions were less frequent for RP-MUS (OR 0.24, 95 % CI 0.07 -
      0.84). Vaginal injuries were more common with TOT than with TVT-O (OR 7.96, 95 %
      CI 1.15 - 157.9). Pain-related complications were more common with TO-MUS than
      with minimally invasive tapes (OR 8.75; 95 % CI 9.02 - 57.90). CONCLUSIONS: MUS
      have similar objective cure rates in the long term and medium term. TO-MUS is
      associated with a lower subjective cure rate than RP-MUS.

PMID- 25990205
TI  - Comparison of two laparoscopic peritoneal vaginoplasty techniques in patients
      with Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the technical
      feasibility and long-term anatomical and functional outcomes of a novel
      laparoscopic vaginoplasty using single peritoneal flap (SPF) and Davydov's
      laparoscopic technique in patients with Mayer-Rokitansky-Kuster-Hauser (MRKH)
      syndrome. METHODS: From September 2004 to September 2013, a comparative study was
      conducted of 98 patients with MRKH syndrome who underwent either laparoscopic
      vaginoplasty using SPF (SPF group, 62 cases) or Davydov's laparoscopic technique
      (Davydov group, 36 cases) in a university-based tertiary care hospital.
      Intraoperative and postoperative parameters and anatomical examination findings
      of the two groups were compared. Functional results were assessed using the
      Female Sexual Function Index (FSFI). RESULTS: All surgical procedures were
      performed successfully, with no intraoperative complications in either group.
      Patients in the SPF group had a significantly shorter operative time and less
      intraoperative blood loss than patients in the Davydov group. The postoperative
      course was identical for all patients in the two groups. The mean length and
      width of the neovagina in the two groups at hospital discharge, the 6-month
      follow-up, and the 12-month follow-up did not differ significantly. There were no
      significant differences between the groups with regard to the postoperative FSFI
      scores at 12 months after surgery. CONCLUSIONS: Although the long-term anatomical
      and functional outcomes of the two laparoscopic peritoneal vaginoplasty
      techniques are similar, laparoscopic vaginoplasty using SPF, which has many
      advantages and is easily performed by the gynecologist, is a more feasible and
      effective approach to creating a neovagina in patients with MRKH syndrome.

PMID- 25990206
TI  - Kielland's forceps: does it increase the risk of anal sphincter injuries? An
      observational study.
AB  - INTRODUCTION AND HYPOTHESIS: Rotational instrumental deliveries are thought to
      carry additional risks compared with non-rotational instrumental deliveries,
      including trauma to maternal tissues, and require specific expertise and
      training. We conducted a retrospective study to investigate the association
      between the type of forceps delivery and maternal perineal trauma, and in
      particular to investigate if Kielland's rotational forceps delivery increases
      obstetric anal sphincter injuries (OASIS). METHODS: This is a retrospective
      observational study of 1,515 women who attended a tertiary maternity unit over a
      period of 5 years and had operative vaginal deliveries primarily or completed by
      forceps. Data were obtained through the hospital's maternity reporting system.
      The severity of maternal perineal trauma, particularly third and fourth-degree
      tears in relation to the type of forceps delivery was explored. Multinomial
      logistic regression models were used to estimate the crude and the adjusted
      relative risks (RR) of sustaining third-degree tears compared with other types of
      vaginal tears. Univariate analyses explored the crude associations between
      relative risks and age, ethnicity, birth weight, type of instrumental delivery
      and operator's experience. A multivariate multinomial logistic regression model
      estimated the adjusted relative risks and included all the previous variables as
      independent covariates. RESULTS: Of the 1,492 women included in the study, 150
      women (77 %) had sustained category 1 tears, 63 women (4 %) had sustained
      category 2 tears and 279 women (19 %) had sustained third-degree tears. There was
      no statistically significant association between the severity of maternal
      perineal trauma and the type of forceps delivery (failed ventouse vs Kielland's
      forceps RR 1.52, p = 0.159 CI 0.84-2.72, Wrigleys vs Kielland's RR 0.59, p =
      0.249, CI 0.24-1.43; Andersons vs Kielland's RR 1.16, p = 0.603, CI 0.65-2.05)
      after adjusting for age, birth weight, BMI, ethnicity and operator experience
      (full list of covariates not included). CONCLUSIONS: The incidence of third- and
      fourth-degree tears following rotational Kielland's forceps delivery and other
      non-rotational forceps deliveries is comparable.

PMID- 25990207
TI  - Disclosures, conflict of interest, and funding issues in urogynecology articles:
      a bibliometric study.
AB  - INTRODUCTION AND HYPOTHESIS: The ethical behavior of authors, editors, and
      journals is increasingly placed in the spotlight, by both the public and the
      research community. Disclosures and conflict of interest (COI) statements of
      publishing authors represent one important aspect. We aimed to unravel the
      current management of disclosures, COI, and funding statements in the
      subspecialty urogynecology. METHODS: A bibliometric study was carried out. We
      included six journals that published urogynecology articles between January and
      December 2013. All original articles, reviews, and opinion articles were assessed
      for the presence of disclosure/COI and funding statements. Information given on
      the official disclosure form was compared with information given in the final
      article (International Urogynecology Journal). RESULTS: All journals investigated
      require disclosure and funding statements in their instructions to authors. Of
      the 434 articles included, almost all contained a disclosure statement (98-100
      %). Funding statements were present in 41-100 % of articles, indicating a
      difference in journal type (50 % on average among urogynecology journals; 75 % on
      average among general gynecology journals). The main source of funding was
      "grants" (58 %), followed by "none" (16 %), "industry" (16 %), and lastly
      "hospital/university" (10 %). Disclosure statements in the article were identical
      to the official disclosure form in 80 % (IUJ). CONCLUSIONS: Disclosure/COI
      statements were included in almost all urogynecology articles investigated. Their
      content, however, is sometimes incomplete and should possibly be monitored more
      closely by journals and authors. Despite universal requirements of journals, the
      reporting of funding seems inconsistent. This issue in addition to the
      completeness of disclosures should be given more attention.

PMID- 25990208
TI  - Laparoscopic supracervical hysterectomy with transcervical morcellation and
      sacrocervicopexy for the treatment of uterine prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: The objective is to describe our surgical approach
      for management of uterine prolapse using 5-mm skin incisions and transcervical
      morcellation. METHODS: This video presents a novel approach for laparoscopic
      supracervical hysterectomy, bilateral salpingectomy, and sacrocervicopexy using
      only 5-mm skin incisions and transcervical morcellation. The procedure begins
      with a laparoscopic supracervical hysterectomy with bilateral salpingectomy. A
      classic intrafascial supracervical hysterectomy (CISH) instrument is then used
      transvaginally to core the endocervical canal. A disposable morcellator is placed
      through the remaining cervix to morcellate the uterus and fallopian tubes.
      Following morcellation, the handle of the morcellator is removed, and it is used
      during the remainder of the surgery as an access cannula for the
      sacrocervicopexy. The polypropylene mesh is introduced through this cannula. It
      is secured to the anterior and posterior vaginal fascia with a suture that is
      also introduced through the transcervical port. At the conclusion of the surgery,
      a previously placed 0 Vicryl purse-string suture at the ectocervix is tied down
      as a cerclage around the cervix once the cannula is removed. CONCLUSIONS: The
      transcervical morcellation technique demonstrated in this video allows the
      surgeon to maintain 5-mm skin incisions and core the endocervical canal during a
      laparoscopic supracervical hysterectomy with sacrocervicopexy.

PMID- 25990209
TI  - Response to the letter to the editor by H.P. Dietz.

PMID- 25990210
TI  - Interlimb coordination in body-weight supported locomotion: A pilot study.
AB  - Locomotion involves complex neural networks responsible for automatic and
      volitional actions. During locomotion, motor strategies can rapidly compensate
      for any obstruction or perturbation that could interfere with forward
      progression. In this pilot study, we examined the contribution of interlimb
      pathways for evoking muscle activation patterns in the contralateral limb when a
      unilateral perturbation was applied and in the case where body weight was
      externally supported. In particular, the latency of neuromuscular responses was
      measured, while the stimulus to afferent feedback was limited. The pilot
      experiment was conducted with six healthy young subjects. It employed the MIT
      Skywalker (beta-prototype), a novel device intended for gait therapy. Subjects
      were asked to walk on the split-belt treadmill, while a fast unilateral
      perturbation was applied mid-stance by unexpectedly lowering one side of the
      split-treadmill walking surfaces. Subject's weight was externally supported via
      the body-weight support system consisting of an underneath bicycle seat and the
      torso was stabilized via a loosely fitted chest harness. Both the weight support
      and the chest harness limited the afferent feedback. The unilateral perturbations
      evoked changes in the electromyographic activity of the non-perturbed
      contralateral leg. The latency of all muscle responses exceeded 100ms, which
      precludes the conjecture that spinal cord alone is responsible for the
      perturbation response. It suggests the role of supraspinal or midbrain level
      pathways at the inter-leg coordination during gait. 

PMID- 25990211
TI  - "Percentaging" contingency tables: It really does matter how you do it.
AB  - Contingency tables display the co-occurrence of categorical variables. The
      frequencies of occurrence in each category of each variable are converted into
      percentages in order to facilitate the interpretation of the relationship between
      the variables. "Percentaging" a contingency table is not easy, however. One has
      to be careful regarding how the percentaging is done (down the columns, across
      the rows, or by total sample size). Using an artificial example and a real-world
      example, we show how percentaging is carried out and how the proper
      interpretation of the findings depends upon the direction in which the
      calculations are performed.

PMID- 25990212
TI  - Cyclin-dependent kinase 11(p110) (CDK11(p110)) is crucial for human breast cancer
      cell proliferation and growth.
AB  - Cyclin-dependent kinases (CDKs) play important roles in the development of many
      types of cancers by binding with their paired cyclins. However, the function of
      CDK11 larger protein isomer, CDK11(p110), in the tumorigenesis of human breast
      cancer remains unclear. In the present study, we explored the effects and
      molecular mechanisms of CDK11(p110) in the proliferation and growth of breast
      cancer cells by determining the expression of CDK11(p110) in breast tumor tissues
      and examining the phenotypic changes of breast cancer cells after CDK11(p110)
      knockdown. We found that CDK11(p110) was highly expressed in breast tumor tissues
      and cell lines. Tissue microarray analysis showed that elevated CDK11(p110)
      expression in breast cancer tissues significantly correlated with poor
      differentiation, and was also associated with advanced TNM stage and poor
      clinical prognosis for breast cancer patients. In vitro knockdown of CDK11(p110)
      by siRNA significantly inhibited cell growth and migration, and dramatically
      induced apoptosis in breast cancer cells. Flow cytometry demonstrated that cells
      were markedly arrested in G1 phase of the cell cycle after CDK11(p110)
      downregulation. These findings suggest that CDK11(p110) is critical for the
      proliferation and growth of breast cancer cells, which highlights CDK11(p110) may
      be a promising therapeutic target for the treatment of breast cancer. 

PMID- 25990213
TI  - Cooperatively transcriptional and epigenetic regulation of sonic hedgehog
      overexpression drives malignant potential of breast cancer.
AB  - Sonic hedgehog (Shh), a ligand of Hedgehog signaling pathway, is considered an
      important oncogene and an exciting potential therapeutic target in several
      cancers. Comprehensive understanding of the regulation mechanism of Shh in cancer
      cells is necessary to find an effective approach to selectively block its
      tumorigenic function. We and others previously demonstrated that nuclear factor
      kappa B (NF-kappaB) activation and promoter hypomethylation contributed to the
      overexpression of Shh. However, the relationship between transcriptional and
      epigenetic regulation of Shh, and their roles in the malignant phenotype of
      cancer cells are still not clearly elucidated. In the present study, our data
      showed that the level of Shh was higher in breast cancer tissues with positive NF
      kappaB nuclear staining and promoter hypomethylation. In addition, survival
      analysis revealed that Shh overexpression, but not hypomethylation and NF-kappaB
      nuclear staining, was a poor prognosis indicator for breast cancers. Moreover, in
      vitro data demonstrated that both NF-kappaB activation and hypomethylation in
      promoter region were positively associated with the overexpression of Shh.
      Mechanistically, the hypomethylation in Shh promoter could facilitate NF-kappaB
      binding to its site, and subsequently cooperate to induce transcription of Shh.
      Furthermore, the biological function data indicated that overexpressed Shh
      enhanced the self-renewal capacity and migration ability of breast cancer cells,
      which could be augmented by promoter demethylation and NF-kappaB activation.
      Overall, our findings reveal multiple and cooperative mechanisms of Shh
      upregulation in cancer cells, and the roles of Shh in tumor malignant behavior,
      thus suggesting a new strategy for therapeutic interventions to reduce Shh in
      tumors and improve patients' prognosis. 

PMID- 25990215
TI  - Fifteen-minute consultation: autoimmune encephalitis.
AB  - Autoimmune encephalitis (AE) is increasingly diagnosed in children, and can
      result in severe long-term disability. We use a clinical case to illustrate the
      core clinical features, initial investigations and management of this potentially
      treatable condition, and describe the common presenting neurological syndromes
      alongside highlighting differences between each autoantibody subtype. 

PMID- 25990214
TI  - Natural variations in OsgammaTMT contribute to diversity of the alpha-tocopherol
      content in rice.
AB  - Tocopherols and tocotrienols, collectively known as tocochromanols, are lipid
      soluble molecules that belong to the group of vitamin E compounds. Among them,
      alpha-tocopherol (alphaTau) is one of the antioxidants with diverse functions and
      benefits for humans and animals. Thus, understanding the genetic basis of these
      traits would be valuable to improve nutritional quality by breeding in rice.
      Genome-wide association study (GWAS) has emerged as a powerful strategy for
      identifying genes or quantitative trait loci (QTL) underlying complex traits in
      plants. To discover the genes or QTLs underlying the naturally occurring
      variations of alphaTau content in rice, we performed GWAS using 1.44 million high
      quality single-nucleotide polymorphisms acquired from re-sequencing of 137
      accessions from a diverse rice core collection. Thirteen candidate genes were
      found across 2-year phenotypic data, among which gamma-tocopherol
      methyltransferase (OsgammaTMT) was identified as the major factor responsible for
      the alphaTau content among rice accessions. Nucleotide variations in the coding
      region of OsgammaTMT were significantly associated with the alphaTau content
      variations, while nucleotide polymorphisms in the promoter region of OsgammaTMT
      also could partly demonstrate the correlation with alphaTau content variations,
      according to our RNA expression analyses. This study provides useful information
      for genetic factors underlying alphaTau content variations in rice, which will
      significantly contribute the research on alphaTau biosynthesis mechanisms and
      alphaTau improvement of rice. 

PMID- 25990216
TI  - Internet-based cognitive behavior therapy for patients with heart failure and
      depressive symptoms: A proof of concept study.
AB  - OBJECTIVE: The aim was (1) to describe the development of a guided internet-based
      CBT (ICBT) program adapted to patients with heart failure (HF) and (2) to
      evaluate the feasibility of the ICBT program in regard to depressive symptoms,
      the time used by health care providers to give feedback, and participants'
      perceptions of the ICBT program. METHOD: A multi-professional team developed the
      program and seven HF patients with depressive symptoms were recruited to the
      study. The Patient Health Questionnaire-9 (PHQ-9) and the Montgomery Asberg
      Depression Rating-Self-rating scale (MADRS-S) were used to measure depression,
      and patients were interviewed about their perceptions of the program. RESULTS:
      Based on research in HF and CBT, a nine-week program was developed. The median
      depression score decreased from baseline to the end of the study (PHQ-9: 11-8.5;
      MADRS-S: 25.5-16.5) and none of the depression scores worsened. Feedback from
      health care providers required approximately 3h per patient. Facilitating
      perceptions (e.g. freedom of time) and demanding perceptions (e.g. part of the
      program demanded a lot of work) were described by the patients. CONCLUSION: The
      program appears feasible and time-efficient. However, the program needs to be
      evaluated in a larger randomized study.

PMID- 25990217
TI  - Editorial: new challenges for in zoonotic and vector-borne diseases - part I.

PMID- 25990218
TI  - Carbonization of a stable beta-sheet-rich silk protein into a pseudographitic
      pyroprotein.
AB  - Silk proteins are of great interest to the scientific community owing to their
      unique mechanical properties and interesting biological functionality. In
      addition, the silk proteins are not burned out following heating, rather they are
      transformed into a carbonaceous solid, pyroprotein; several studies have
      identified potential carbon precursors for state-of-the-art technologies.
      However, no mechanism for the carbonization of proteins has yet been reported.
      Here we examine the structural and chemical changes of silk proteins
      systematically at temperatures above the onset of thermal degradation. We find
      that the beta-sheet structure is transformed into an sp(2)-hybridized carbon
      hexagonal structure by simple heating to 350  degrees C. The pseudographitic
      crystalline layers grew to form highly ordered graphitic structures following
      further heating to 2,800  degrees C. Our results provide a mechanism for the
      thermal transition of the protein and demonstrate a potential strategy for
      designing pyroproteins using a clean system with a catalyst-free aqueous wet
      process for in vivo applications. 

PMID- 25990219
TI  - Double Back Cut in Post-mastectomy Breast Skin (Fish-Shaped Skin Paddle) in
      Delayed Pedicled TRAM Flap Breast Reconstruction.
AB  - Breast reconstruction has become standard of care for female patients with breast
      cancer. The transverse rectus abdominis musculo-cutaneous flap (TRAMf) is the
      most common method of immediate or delayed autologous breast reconstruction
      following mastectomy. We share our experience with modified, double back cut of
      post-mastectomy skin in delayed pedicled TRAMf breast reconstruction, resulting
      in fish-shaped skin paddle. This sort of back cut is a simple, reliable way to
      obtain a natural, esthetically pleasant breast mound with inconspicuous hidden
      scars.

PMID- 25990222
TI  - Patient-Important Outcomes in the Long-Term Treatment of Bipolar Disorder: A
      Mixed-Methods Approach Investigating Relative Preferences and a Proposed
      Taxonomy.
AB  - BACKGROUND: In patient-centered healthcare, the assessment and selection of
      treatment should be based on outcomes important to patients and the relative
      importance patients place on these outcomes. The evidence base on long-term
      treatment outcomes important to patients with bipolar disorder is inconclusive.
      OBJECTIVE: The aim of this study was to investigate the relative importance of
      patient-important outcomes in bipolar disorder, and to construct a holistic and
      logically sound shortlist of treatment outcomes relevant in the evaluation and
      selection of pharmacological treatment in bipolar disorder. METHOD: Overall, 22
      outpatients from southern and eastern Norway participated in four focus groups,
      and suggested outcomes important in treatment decisions. Quantitative, relative
      importance weights for treatment outcomes identified in literature reviews were
      elicited from each participant, employing a self-explicated approach (SEA). The
      method combined a ranking- and rating-stated preference exercise and resulted in
      a 0-100 SEA-score for each outcome. RESULTS: Outcomes from the literature
      accommodated the outcomes suggested in the focus groups. Mean age in the sample
      was 42 years and 64% were women. All patients completed the exercises with
      consistent results. The most important outcomes were severe depression (median
      SEA 95 [interquartile range 26]), severe mania (76 [40]), quality of life (65
      [53]), work/school functioning (58 [48]), and social functioning (54 [50]).
      Avoiding severe mania was significantly more important to patients with bipolar
      disorder type I compared with patients with type II. Outcome scores correlated
      strongly (p < 0.01) across the ranking and rating exercises. Based on the
      results, a simplified and consistent set of outcomes was constructed.
      CONCLUSIONS: Patients' preferences for outcomes in the long-term treatment of
      bipolar disorder vary considerably. To advance patient-centered healthcare, we
      propose that researchers, clinical guideline producers, and patient-clinician
      dyads integrate a taxonomy of patient-important outcomes, such as constructed in
      this study, when assessing treatment options.

PMID- 25990223
TI  - Australian dentists: characteristics of those who employ or are willing to employ
      oral health therapists.
AB  - BACKGROUND: There has been an increase in the availability of oral health
      therapists (OHTs) in the oral health workforce in the last decade. The impact
      these clinicians will have on the oral health of the general public is dependent
      on access pathways and utilization. This study aimed to profile Australian
      dentists who employ or are willing to employ OHTs and to explore the degree of
      association between dentist characteristics and employment decisions. METHODS:
      This cross-sectional study used a random sample of Australian dentists (n = 1169)
      from the Federal Australian Dental Association register in 2009. Participants
      were sent a postal questionnaire capturing dentist characteristics and oral
      health practitioner employment information. RESULTS: An adjusted response rate of
      55% was obtained. Dentists willing to employ OHTs included non-metropolitan
      dentists, dentists in multiple surgery practices and those considering practice
      expansion. Age, gender and sector of practice were not significantly associated
      with retrospective employment decisions or willingness to employ in the future.
      CONCLUSIONS: Certain characteristics of dentists or of their practice are
      associated with their history of employment and willingness to employ OHTs.
      Employment decisions are more commonly related to entrepreneurial aspirations
      (expressed as a willingness to expand), sector of practice, surgery capacity and
      regionality over gender and age. Understanding the factors that influence the
      employment of OHTs is important in enhancing access pathways to the services
      provided by OHTs.

PMID- 25990221
TI  - NOS Inhibition Modulates Immune Polarization and Improves Radiation-Induced Tumor
      Growth Delay.
AB  - Nitric oxide synthases (NOS) are important mediators of progrowth signaling in
      tumor cells, as they regulate angiogenesis, immune response, and immune-mediated
      wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of
      wound response. We hypothesized that radiation therapeutic efficacy could be
      improved by targeting NOS following tumor irradiation. Herein, we show enhanced
      radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not
      immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post
      IR with the constitutive NOS inhibitor N(G)-nitro-l-arginine methyl ester (L
      NAME). These results suggest a requirement of T cells for improved radiation
      tumor response. In support of this observation, tumor irradiation induced a rapid
      increase in the immunosuppressive Th2 cytokine IL10, which was abated by post-IR
      administration of L-NAME. In vivo suppression of IL10 using an antisense IL10
      morpholino also extended the tumor growth delay induced by radiation in a manner
      similar to L-NAME. Further examination of this mechanism in cultured Jurkat T
      cells revealed L-NAME suppression of IR-induced IL10 expression, which
      reaccumulated in the presence of exogenous NO donor. In addition to L-NAME, the
      guanylyl cyclase inhibitors ODQ and thrombospondin-1 also abated IR-induced IL10
      expression in Jurkat T cells and ANA-1 macrophages, which further suggests that
      the immunosuppressive effects involve eNOS. Moreover, cytotoxic Th1 cytokines,
      including IL2, IL12p40, and IFNgamma, as well as activated CD8(+) T cells were
      elevated in tumors receiving post-IR L-NAME. Together, these results suggest that
      post-IR NOS inhibition improves radiation tumor response via Th1 immune
      polarization within the tumor microenvironment.

PMID- 25990224
TI  - Postmortem image-guided biopsy for less-invasive diagnosis of congenital
      intracranial teratoma.

PMID- 25990225
TI  - Postpartum Mental Health Promotion: Perspectives from Mothers and Home Visitors.
AB  - OBJECTIVE: The object of this study was to examine the implementation of the
      Towards Flourishing Mental Health Promotion Strategy, a demonstration project
      designed to promote the mental well-being of parents and their children that was
      added to an existing public health home visiting program. DESIGN AND SAMPLE:
      Structured interviews were conducted with program stakeholders including 13 women
      receiving home visiting services in the postpartum period and 6 home visitors.
      MEASURES: Thematic analysis of individual transcripts was conducted and results
      were compiled according to common themes. RESULTS: The results indicate that
      women and home visitors perceived the integration of a mental health promotion
      strategy into an existing public health program as feasible, acceptable and
      useful. The strategy provides a mechanism for women and home visitors to dialog
      about mental health and appears to have early positive impacts on the women.
      Factors that facilitated and impeded the successful implementation of the
      strategy are described. CONCLUSION: These results point to promising strategies
      to reach women early in the postpartum period to support their mental health.
      They also shed light on the barriers to supporting mental health, indicating the
      need to address stigma related to mental health and the social determinants of
      health.

PMID- 25990226
TI  - Novel polymeric bioerodable microparticles for prolonged-release intrathecal
      delivery of analgesic agents for relief of intractable cancer-related pain.
AB  - Intractable cancer-related pain complicated by a neuropathic component due to
      nerve impingement is poorly alleviated even by escalating doses of a strong
      opioid analgesic. To address this unmet medical need, we developed sustained
      release, bioerodable, hydromorphone (potent strong opioid)- and ketamine
      (analgesic adjuvant)-loaded microparticles for intrathecal (i.t.)
      coadministration. Drug-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles
      were prepared using a water-in-oil-in-water method with evaporation.
      Encapsulation efficiency of hydromorphone and ketamine in PLGA (50:50)
      microparticles was 26% and 56%, respectively. Microparticles had the desired size
      range (20-60 MUm) and in vitro release was prolonged at >=28 days. Microparticles
      were stable for >=6 months when stored refrigerated protected from light in a
      desiccator. Desirably, i.t. injected fluorescent dye-labeled PLGA microparticles
      in rats remained in the lumbar region for >=7 days. In a rat model of neuropathic
      pain, i.t. coinjection of hydromorphone- and ketamine-loaded microparticles (each
      1 mg) produced analgesia for 8 h only. Possible explanations include inadequate
      release of ketamine and/or hydromorphone into the spinal fluid, and/or
      insufficient ketamine loading to prevent development of analgesic tolerance to
      the released hydromorphone. As sub-analgesic doses of i.t. ketamine at 24-48 h
      intervals restored analgesia on each occasion, insufficient ketamine loading
      appears problematic. We will investigate these issues in future work.

PMID- 25990227
TI  - Protective Effect of Tat PTD-Hsp27 Fusion Protein on Tau Hyperphosphorylation
      Induced by Okadaic Acid in the Human Neuroblastoma Cell Line SH-SY5Y.
AB  - Alzheimer's disease (AD) is an age-related disorder that causes a loss of brain
      function. Hyperphosphorylation of tau and the subsequent formation of
      intracellular neurofibrillary tangles (NFTs) are implicated in the pathogenesis
      of AD. Hyperphosphorylated tau accumulates into insoluble paired helical
      filaments that aggregate into NFTs; therefore, regulation of tau phosphorylation
      represents an important treatment approach for AD. Heat shock protein 27 (Hsp27)
      plays a specific role in human neurodegenerative diseases; however, few studies
      have examined its therapeutic effect. In this study, we induced tau
      hyperphosphorylation using okadaic acid, which is a protein phosphatase
      inhibitor, and generated a fusion protein of Hsp27 and the protein transduction
      domain of the HIV Tat protein (Tat-Hsp27) to enhance the delivery of Hsp27. We
      treated Tat-Hsp27 to SH-SY5Y neuroblastoma cells for 2 h; the transduction level
      was proportional to the Tat-hsp27 concentration. Additionally, Tat-Hsp27 reduced
      the level of hyperphosphorylated tau and protected cells from apoptotic cell
      death caused by abnormal tau aggregates. These results reveal that Hsp27
      represents a valuable protein therapeutic for AD. 

PMID- 25990229
TI  - The sacred cow status of the NHS.

PMID- 25990228
TI  - Up-Regulation of PKM2 Relates to Retinal Ganglion Cell Apoptosis After Light
      Induced Retinal Damage in Adult Rats.
AB  - Pyruvate kinase isozyme type M2 (PKM2), a key glycolytic enzyme, which is
      involved in ATP generation and pyruvate production, participates in tumor
      metabolism, growth, and other multiple cellular processes. However, one
      attractive biological function of PKM2 is that it translocates to the nucleus and
      induces cell apoptosis. Recently, increased PKM2 has been found in age-related
      macular degeneration (AMD), but little is known regarding its function in the AMD
      pathophysiology. To investigate whether PKM2 participated in retinal
      degeneration, we performed a light-induced retinal damage model in adult rats.
      Western blot and immunohistochemistry analysis showed a significant up-regulation
      of PKM2 in retinal ganglion cells (RGCs) layer (GCL) after light exposure.
      Immunofluorescent labeling indicated that PKM2 located mainly in RGCs. Co
      localization of PKM2 and active caspase-3 as well as TUNEL in RGCs suggested that
      PKM2 might participate in RGC apoptosis. In addition, the expression patterns of
      cyclin D1 and phosphorylated extracellular signal-regulated kinase (p-ERK) were
      parallel with that of PKM2. Furthermore, PKM2, cyclin D1, and active caspase-3
      protein expression decreased by intravitreal injection of U0126, a highly
      selective inhibitor of MAPK/ERK kinase. Collectively, we hypothesized that PKM2
      might participate in RGC apoptosis after light-induced retinal damage medicated
      by p-ERK through cycle re-entry mechanism. 

PMID- 25990230
TI  - Confidentiality and data sharing: vulnerabilities of the Mexican Genomics
      Sovereignty Act.
AB  - A law known as "Genomic Sovereignty Act", instituted in 2011, regulates research
      on the human genome in Mexico. This law establishes Government regulations for
      the exportation of DNA samples from Mexican nationals for population genetics
      studies. The Genomic Sovereignty Act protects fundamental human values, as
      confidentiality and non-discrimination based on personal genetic information. It
      also supports the development of the genome-based medical biotechnology and the
      bio-economy. Current laws for the protection of the genomic confidentiality,
      however, are inexplicit and insufficient, and the legal and technological
      instruments are primitive and insufficient to safeguard this bioethical
      principle. In addition, this law may undermine efforts of the national and
      international scientific communities to cooperate with big-data analysis for the
      development of the genome-based biomedical sciences. The argument of this article
      is that deficiencies in the protection of the confidentiality of genomic
      information and limitations in data sharing severely weaken the objectives and
      scope of the Genomic Sovereignty Act. In addition, the Act may compromise the
      national biomedical development and the international cooperation for research
      and development in the field of human genomics. 

PMID- 25990232
TI  - Clindamycin resistant emm33 Streptococcus pyogenes emerged among invasive
      infections in Helsinki metropolitan area, Finland, 2012 to 2013.
AB  - In 2012, blood, skin and soft tissue infections caused by clindamycin resistant
      Streptococcus pyogenes (group A streptococcus; GAS) appeared to be increasing in
      the Helsinki metropolitan area. We compared monthly percentages of clindamycin
      resistant isolates in the area between 2012 and 2013, with those in 2010 and
      2011. Resistance frequency in terms of patient age was also studied. We reviewed
      the medical records of bacteraemic cases in 2012 and 2013 and linked the data to
      emm types. To inform on the emm distribution among GAS isolated from skin and
      soft tissue infections during the epidemic, GAS isolates of one month (March
      2013) were emm typed. For GAS blood, skin, and soft tissue isolates taken
      together, the proportions of clindamycin resistant isolates were significantly
      higher in 2012 and 2013 (23% and 17%, respectively) compared with the two
      previous years (3%, p<0,001). The erythromycin resistance percentages were almost
      equal to clindamycin (22% and 17%) in 2012 and 2013, respectively. Clindamycin
      resistance was most frequent in GAS isolates of 40 to 60 year-old patients
      (148/417; 36%). Among clindamycin resistant isolates, 12 of 14 blood isolates
      from 2012 to 2013, and 11 of 13 skin and soft tissue isolates from March 2013,
      were emm33. Emm33 GAS bacteraemia was associated with clindamycin and
      erythromycin resistance (odds ratio (OR): 7.0; 95% confidence interval (CI): 1.9
      25.3). Infection focus was mainly the skin; either cellulitis (7/12) or
      necrotising fasciitis (3/12). All emm33 GAS isolates harboured the ermTR
      resistance gene with constitutive macrolides, lincosamides and streptogramines B
      (MLS(B)) phenotype. Emm33 GAS was responsible for the higher proportion of
      clindamycin resistance in skin, soft tissue, and blood isolates locally in 2012
      and 2013.

PMID- 25990231
TI  - Landscape and climatic characteristics associated with human alveolar
      echinococcosis in France, 1982 to 2007.
AB  - Human alveolar echinococcosis (AE) is a severe hepatic disease caused by
      Echinococcus multilocularis. In France, the definitive and intermediate hosts of
      E. multilocularis (foxes and rodents, respectively) have a broader geographical
      distribution than that of human AE. In this two-part study, we describe the link
      between AE incidence in France between 1982 and 2007 and climatic and landscape
      characteristics. National-level analysis demonstrated a dramatic increase in AE
      risk in areas with very cold winters and high annual rainfall levels. Notably,
      52% (207/401) of cases resided in French communes (smallest French administrative
      level) with a mountain climate. The mountain climate communes displayed a 133
      fold (95% CI: 95-191) increase in AE risk compared with communes in which the
      majority of the population resides. A case-control study performed in the most
      affected areas confirmed the link between AE risk and climatic factors. This arm
      of the study also revealed that populations residing in forest or pasture areas
      were at high risk of developing AE. We therefore hypothesised that snow-covered
      ground may facilitate predators to track their prey, thus increasing E.
      multilocularis biomass in foxes. Such climatic and landscape conditions could
      lead to an increased risk of developing AE among humans residing in nearby areas.

PMID- 25990234
TI  - Public health response to two incidents of confirmed MERS-CoV cases travelling on
      flights through London Heathrow Airport in 2014 - lessons learnt.
AB  - In May 2014, Public Health England was alerted to two separate laboratory
      confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV)
      infection who transited through London Heathrow Airport while symptomatic on
      flights from Saudi Arabia to the United States of America. We present the
      rationale for the public health response to both incidents, and report results of
      contact tracing. Following a risk assessment, passengers seated two seats around
      the cases were prioritised for contact tracing and a proactive media approach was
      used to alert all passengers on the planes of their possible exposure in both
      incidents. In total, 64 United Kingdom (UK) residents were successfully
      contacted, 14 of whom were sat in the priority area two seats all around the
      case(s). Five passengers reported respiratory symptoms within 14 days of the
      flight, but all tested were negative for MERS-CoV. Details of non-UK residents
      were passed on to relevant World Health Organization International Health
      Regulation focal points for follow-up, and no further cases were reported back.
      Different approaches were used to manage contact tracing for each flight due to
      variations in the quality and timeliness of the passenger contact information
      provided by the airlines involved. No evidence of symptomatic onward transmission
      was found.

PMID- 25990233
TI  - Haemagglutinin mutations and glycosylation changes shaped the 2012/13 influenza
      A(H3N2) epidemic, Houston, Texas.
AB  - While the early start and higher intensity of the 2012/13 influenza A virus (IAV)
      epidemic was not unprecedented, it was the first IAV epidemic season since the
      2009 H1N1 influenza pandemic where the H3N2 subtype predominated. We directly
      sequenced the genomes of 154 H3N2 clinical specimens collected throughout the
      epidemic to better understand the evolution of H3N2 strains and to inform the
      H3N2 vaccine selection process. Phylogenetic analyses indicated that multiple co
      circulating clades and continual antigenic drift in the haemagglutinin (HA) of
      clades 5, 3A, and 3C, with the evolution of a new 3C subgroup (3C-2012/13), were
      the driving causes of the epidemic. Drift variants contained HA substitutions and
      alterations in the potential N-linked glycosylation sites of HA. Antigenic
      analysis demonstrated that viruses in the emerging subclade 3C.3 and subgroup 3C
      2012/13 were not well inhibited by antisera generated against the 3C.1 vaccine
      strains used for the 2012/13 (A/Victoria/361/2011) or 2013/14 (A/Texas/50/2012)
      seasons. Our data support updating the H3N2 vaccine strain to a clade 3C.2 or
      3C.3-like strain or a subclade that has drifted further. They also underscore the
      challenges in vaccine strain selection, particularly regarding HA and
      neuraminidase substitutions derived during laboratory passage that may alter
      antigenic testing accuracy.

PMID- 25990235
TI  - The Italian registry of cystic echinococcosis (RIEC): the first prospective
      registry with a European future.
AB  - Cystic echinococcosis (CE), a worldwide zoonosis, is highly endemic in southern
      and eastern Europe. Its actual prevalence is unknown due to the lack of efficient
      reporting systems designed to take into account the particular features of the
      disease. Neglect of CE makes diagnosis and clinical management difficult outside
      referral centres, with inconsistencies in clinical practice and often unnecessary
      procedures carried out that have associated risks and costs. The Italian registry
      of CE (RIEC) is a prospective multicentre registry of CE patients seen from
      January 2012 in Italian health centres; data are voluntarily submitted to the
      registry. Its aims are to show the prevalence of CE in Italy, bring the
      importance of this infection to the attention of health authorities, encourage
      public health policies towards its control, and stimulate biological,
      epidemiological and clinical research on CE. From January 2012 to February 2014,
      a total 346 patients were enrolled in 11 centres, outnumbering national reports
      of many CE-endemic European countries. We discuss preliminary data and challenges
      of the RIEC, template for the European registry of CE, which has been implemented
      within the Seventh Framework Programme project HERACLES (Human cystic
      Echinococcosis ReseArch in CentraL and Eastern Societies) since September 2014.

PMID- 25990236
TI  - ECDC adds new pages to online directory on infection prevention and control.

PMID- 25990237
TI  - The Americas region declares that rubella has been eliminated.

PMID- 25990240
TI  - Developing effective policy strategies to retain health workers in rural
      Bangladesh: a policy analysis.
AB  - INTRODUCTION: Retention of human resources for health (HRH), particularly
      physicians and nurses in rural and remote areas, is a major problem in
      Bangladesh. We reviewed relevant policies and provisions in relation to HRH
      aiming to develop appropriate rural retention strategies in Bangladesh. METHODS:
      We conducted a document review, thorough search and review of relevant literature
      published from 1971 through May 2013, key informant interviews with policy elites
      (health policy makers, managers, researchers, etc.), and a roundtable discussion
      with key stakeholders and policy makers. We used the World Health Organization's
      (WHO's) guidelines as an analytical matrix to examine the rural retention
      policies under 4 domains, i) educational, ii) regulatory, iii) financial, and iv)
      professional and personal development, and 16 sub-domains. RESULTS: Over the past
      four decades, Bangladesh has developed and implemented a number of health-related
      policies and provisions concerning retention of HRH. The district quota system in
      admissions is in practice to improve geographical representation of the students.
      Students of special background including children of freedom fighters and tribal
      population have allocated quotas. In private medical and nursing schools, at
      least 5% of seats are allocated for scholarships. Medical education has a
      provision for clinical rotation in rural health facilities. Further, in the
      public sector, every newly recruited medical doctor must serve at least 2 years
      at the upazila level. To encourage serving in hard-to-reach areas, particularly
      in three Hill Tract districts of Chittagong division, the government provides an
      additional 33% of the basic salary, but not exceeding US$ 38 per month. This
      amount is not attractive enough, and such provision is absent for those working
      in other rural areas. Although the government has career development and
      promotion plans for doctors and nurses, these plans are often not clearly
      specified and not implemented effectively. CONCLUSION: The government is
      committed to address the rural retention problem as shown through the formulation
      and implementation of related policies and strategies. However, Bangladesh needs
      more effective policies and provisions designed specifically for attraction,
      deployment, and retention of HRH in rural areas, and the execution of these
      policies and provisions must be monitored and evaluated effectively.

PMID- 25990241
TI  - Regulation of miR-24, miR-30b, and miR-142-3p during macrophage and dendritic
      cell differentiation potentiates innate immunity.
AB  - miRNAs are ubiquitous regulators of human biology. Parallel profiling of in vitro
      monocyte-to-Mphi and monocyte-to-DC differentiation revealed static, convergent,
      and divergent expression of miRNA. Bioinformatic and network analysis of
      differentially expressed miRNAs implicated miR-24, miR-30b, and miR-142-3p as
      negative regulators of intracellular signaling pathways, triggered not only by
      differentiation factors (M-CSF/GM-CSF/IL-4) but also from PRRs. Manipulation of
      miR-24, miR-30b, and miR-142-3p expression during the differentiation of mD-Mphi
      and mD-DC differentiation had minimal impact on the acquisition of phenotype but
      significantly abrogated the ability of these cells to mount inflammatory
      responses to pathogen-associated stimuli. Forced expression of these miRNAs,
      which are down-regulated during differentiation, inhibited release of
      inflammatory cytokines [TNF-alpha, IL-12(p40), IL-6] upon stimulation with LPS.
      Functional analysis revealed overlapping mechanisms of inhibition, including
      surface expression of TLR4/CD14/MD-1 and intracellular PKCalpha/NF-kappaB
      activation. Potential intermediary targets of the TLR4-NF-kappaB axis included
      members of the PI3K and MAPK families and PKC isoforms. These results demonstrate
      the requirement of miR-24, miR-30b, and miR-142-3p down-regulation for the
      generation of fully functional Mphis and DCs. 

PMID- 25990242
TI  - Differential expression of mannose-6-phosphate receptor regulates T cell
      contraction.
AB  - CD8(+) T cells provide protection against pathogens and cancer. After
      encountering a pathogenic antigen, CD8(+) T cells undergo a triphasic program of
      rapid proliferation, contraction, and memory formation. Most (~90-95%) CD8(+) T
      cells die after vigorous proliferation in the T cell contraction phase, yet the
      mechanism that triggers apoptotic T cell death remains elusive. This study tested
      the hypothesis that differential cell-surface expression of M6PR, a
      multifunctional receptor that regulates lysozyme biogenesis, but also uptakes
      apoptosis-inducing serine-protease Gzm-B, critically determines life vs. death
      decisions in T cells. We demonstrate that M6PR-expression on CD8(+) T cell
      surfaces is dynamically regulated during LmOVA bacterial infection. Notably, time
      lapse, confocal microscopy and flow cytometry confirms that M6PR(low) effectors,
      but not M6PR(high) effectors, escape Gzm-B lethal-hit derived from CD4(+)25(+)
      Treg cells. Adoptive cotransfer of M6PR(low) effectors and M6PR(high) effectors
      sorted from LmOVA-infected, congenic mice at the peak of CD8(+) T cell response,
      reveals that M6PR(low) effectors with the CD8(+) T cell memory precursor
      phenotype preferentially survive the CD8(+) T cell contraction and differentiate
      into functional, long-lasting memory CD8(+) T cells. Taken together, our data
      provide the first evidence, to our knowledge, that selective M6PR down-regulation
      has a critical role in CD8(+) T cell survival, and our findings have implications
      for efficient vaccine design and immunotherapy. 

PMID- 25990243
TI  - Inflammatory environment and oxidized LDL convert circulating human proangiogenic
      cells into functional antigen-presenting cells.
AB  - The function of human circulating PACs has been described extensively. However,
      little focus has been placed on understanding how these cells differ in their
      functions in the presence of microenvironments mimicking vascular inflammation.
      We hypothesized that exposure to proinflammatory cytokines or the oxLDL, an
      autoantigen abundant in advanced atherosclerotic plaques, converts PACs into
      immune-modulating/proinflammatory cells. Hence, we examined the effect of oxLDL
      and inflammatory stimuli on their phenotype by use of a functional genomics model
      based on secretome and whole genome transcriptome profiling. PACs obtained from
      culturing a PBMC fraction in angiogenic medium were primed with DC
      differentiation cytokines and then exposed to proinflammatory cytokines or oxLDL.
      Under these conditions, PACs converted into APCs, expressed maturation markers
      CD80 and CD83, and showed an increased up-regulation of CD86. APCcy and APCox
      induced a robust T cell BrdU incorporation. Despite a similar ability to induce
      lymphocyte proliferation, APCcy and APCox differed for the secretory pathway and
      mRNA expression. Analysis of the differentially expressed genes identified 4 gene
      "clusters," showing reciprocal modulation in APCcy vs. APCox, justifying,
      according to functional genomics analyses, a different putative function of the
      cells in antigen processing. Together, these data show that treatment with
      inflammatory cytokines or oxLDL converts human PAC phenotypes and functions into
      that of APCs with similar lymphocyte-activating ability but distinct maturation
      degree and paracrine functions. 

PMID- 25990244
TI  - Low DICER1 expression is associated with attenuated neutrophil differentiation
      and autophagy of NB4 APL cells.
AB  - Successful myeloid differentiation depends on the expression of a series of
      miRNAs. Thus, it is hardly surprising that miRNAs are globally repressed in AML,
      a disease mainly characterized by a block in cellular myeloid differentiation.
      Studies investigating the mechanisms for low miRNA expression in AML has mostly
      focused on altered transcriptional regulation or deletions, whereas defective
      miRNA processing has received less attention. In this study, we report that the
      expression of the key miRNA processing enzyme DICER1 is down-regulated in primary
      AML patient samples and healthy CD34(+) progenitor cells as compared with
      granulocytes. In line with these findings, Dicer1 expression was induced
      significantly in AML cell lines upon neutrophil differentiation. The knocking
      down of DICER1 in AML cells significantly attenuated neutrophil differentiation,
      which was paralleled by decreased expression of miRNAs involved in this process.
      Moreover, we found that inhibiting DICER1 attenuated the activation of autophagy,
      a cellular recycling process that is needed for proper neutrophil differentiation
      of AML cells. Our results clearly indicate that DICER1 plays a novel role in
      neutrophil differentiation as well as in myeloid autophagy of AML cells. 

PMID- 25990245
TI  - The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release.
AB  - Neutrophil granule exocytosis is crucial for host defense and inflammation.
      Neutrophils contain 4 types of granules, the exocytotic release of which is
      differentially regulated. This exocytosis is known to be driven by diverse
      mediators, including calcium and nucleotides, but the precise molecular mechanism
      remains largely unknown. We show in the present study that voltage-gated proton
      (Hv) channels are necessary for the proper release of azurophilic granules in
      neutrophils. On activation of NADPH oxidase by PMA and IgG, neutrophils derived
      from Hvcn1 gene knockout mouse exhibited greater secretion of MPO and elastase
      than WT cells. In contrast, release of LTF enriched in specific granules was not
      enhanced in these cells. The excess release of azurophilic granules in Hv1/VSOP
      deficient neutrophils was suppressed by inhibiting NADPH oxidase activity and, in
      part, by valinomycin, a potassium ionophore. In addition, Hv1/VSOP-deficient mice
      exhibited more severe lung inflammation after intranasal Candida albicans
      infection than WT mice. These findings suggest that the Hv channel acts to
      specifically dampen the release of azurophilic granules through, in part, the
      suppression of increased positive charges at the plasma membrane accompanied by
      the activation of NADPH oxidase in neutrophils. 

PMID- 25990247
TI  - The Danish cancer pathway for patients with serious non-specific symptoms and
      signs of cancer-a cross-sectional study of patient characteristics and cancer
      probability.
AB  - BACKGROUND: A Danish cancer pathway has been implemented for patients with
      serious non-specific symptoms and signs of cancer (NSSC-CPP). The initiative is
      one of several to improve the long diagnostic interval and the poor survival of
      Danish cancer patients. However, little is known about the patients investigated
      under this pathway. We aim to describe the characteristics of patients referred
      from general practice to the NSSC-CPP and to estimate the cancer probability and
      distribution in this population. METHODS: A cross-sectional study was performed,
      including all patients referred to the NSSC-CPP at the hospitals in Aarhus or
      Silkeborg in the Central Denmark Region between March 2012 and March 2013. Data
      were based on a questionnaire completed by the patient's general practitioner
      (GP) combined with nationwide registers. Cancer probability was the percentage of
      new cancers per investigated patient. Associations between patient
      characteristics and cancer diagnosis were estimated with prevalence rate ratios
      (PRRs) from a generalised linear model. RESULTS: The mean age of all 1278
      included patients was 65.9 years, and 47.5 % were men. In total, 16.2 % of all
      patients had a cancer diagnosis after six months; the most common types were lung
      cancer (17.9 %), colorectal cancer (12.6 %), hematopoietic tissue cancer (10.1 %)
      and pancreatic cancer (9.2 %). All patients in combination had more than 80
      different symptoms and 51 different clinical findings at referral. Most symptoms
      were non-specific and vague; weight loss and fatigue were present in more than
      half of all cases. The three most common clinical findings were 'affected general
      condition' (35.8 %), 'GP's gut feeling' (22.5 %) and 'findings from the abdomen'
      (13.0 %). A strong association was found between GP-estimated cancer risk at
      referral and probability of cancer. CONCLUSIONS: In total, 16.2 % of the patients
      referred through the NSSC-CPP had cancer. They constituted a heterogeneous group
      with many different symptoms and clinical findings. The GP's gut feeling was a
      common reason for referral which proved to be a strong predictor of cancer. The
      GP's overall estimation of the patient's risk of cancer at referral was
      associated with the probability of finding cancer.

PMID- 25990246
TI  - Identification of targets for rational pharmacological therapy in childhood
      craniopharyngioma.
AB  - INTRODUCTION: Pediatric adamantinomatous craniopharyngioma (ACP) is a
      histologically benign but clinically aggressive brain tumor that arises from the
      sellar/suprasellar region. Despite a high survival rate with current surgical and
      radiation therapy (75-95 % at 10 years), ACP is associated with debilitating
      visual, endocrine, neurocognitive and psychological morbidity, resulting in
      excheptionally poor quality of life for survivors. Identification of an effective
      pharmacological therapy could drastically decrease morbidity and improve long
      term outcomes for children with ACP. RESULTS: Using mRNA microarray gene
      expression analysis of 15 ACP patient samples, we have found several
      pharmaceutical targets that are significantly and consistently overexpressed in
      our panel of ACP relative to other pediatric brain tumors, pituitary tumors,
      normal pituitary and normal brain tissue. Among the most highly expressed are
      several targets of the kinase inhibitor dasatinib - LCK, EPHA2 and SRC; EGFR
      pathway targets - AREG, EGFR and ERBB3; and other potentially actionable cancer
      targets - SHH, MMP9 and MMP12. We confirm by western blot that a subset of these
      targets is highly expressed in ACP primary tumor samples. CONCLUSIONS: We report
      here the first published transcriptome for ACP and the identification of targets
      for rational therapy. Experimental drugs targeting each of these gene products
      are currently being tested clinically and pre-clinically for the treatment of
      other tumor types. This study provides a rationale for further pre-clinical and
      clinical studies of novel pharmacological treatments for ACP. Development of
      mouse and cell culture models for ACP will further enable the translation of
      these targets from the lab to the clinic, potentially ushering in a new era in
      the treatment of ACP.

PMID- 25990248
TI  - Normal-weight obesity is associated with increased risk of subclinical
      atherosclerosis.
AB  - BACKGROUND: Subjects with normal body mass index (BMI) but elevated amounts of
      body fat (normal-weight obesity; NWO) show cardiometabolic dysregulation compared
      to subjects with normal BMI and normal amounts of body fat (normal-weight lean;
      NWL). In this study, we aimed to evaluate whether NWO individuals have higher
      rates of subclinical atherosclerosis compared to NWL subjects. METHODS: From a
      large-scale health checkup system, we identified 2078 normal weight (18.5 <= BMI
      < 25 kg/m(2)) subjects with no previous history of coronary artery disease who
      underwent analysis of atherosclerosis using coronary computed tomography
      angiography (CCTA) and pulse wave velocity (PWV). NWO was defined as normal BMI
      and highest tertile of body fat percentage by sex (men >= 25. 4 % and women >=
      31.4 %). CCTA was performed using a 64-detector row CT. A plaque was defined as a
      structure >1 mm(2) within and/or adjacent to the vessel lumen and classified
      according to the presence/proportion of intraplaque calcification. RESULTS: NWO
      subjects (n = 283) demonstrated metabolic dysregulation compared to NWL
      individuals (n = 1795). After adjusting for age, sex, and smoking, NWO
      individuals showed higher PWV values than NWL individuals (1474.0 +/- 275.4 vs.
      1380.7 +/- 234.3 cm/s, p = 0.006 by ANCOVA). Compared with NWL subjects, NWO
      subjects had a higher prevalence of soft plaques even after age, sex, and smoking
      adjustment (21.6% vs. 14.5%, p = 0.039 by ANCOVA). The PWV value and the
      log{(number of segments with plaque) + 1} showed a positive correlation with
      numerous parameters such as age, systolic blood pressure, visceral fat, fasting
      glucose level, serum triglyceride level, and C-reactive protein (CRP) in contrast
      to the negative correlation with high-density lipoprotein-cholesterol level. The
      visceral fat was an independent determinant of log{(number of segments with
      plaque) + 1} (beta = 0.027, SE = 0.011, p = 0.016) even after adjustment for
      other significant factors. Most importantly, NWO was an independent risk factor
      for the presence of soft plaques (odds ratio 1.460, 95 % confidence interval
      1.027-2.074, p = 0.035) even after further adjustment for multiple factors
      associated with atherosclerosis (blood pressure, blood glucose, lipid level, CRP,
      medication, smoking status, physical activity). CONCLUSIONS: NWO individuals
      carry a higher incidence of subclinical atherosclerosis compared with NWL
      individuals, regardless of other clinical risk factors for atherosclerosis.

PMID- 25990249
TI  - Nurses' worry or concern and early recognition of deteriorating patients on
      general wards in acute care hospitals: a systematic review.
AB  - INTRODUCTION: Nurses often recognize deterioration in patients through intuition
      rather than through routine measurement of vital signs. Adding the 'worry or
      concern' sign to the Rapid Response System provides opportunities for nurses to
      act upon their intuitive feelings. Identifying what triggers nurses to be worried
      or concerned might help to put intuition into words, and potentially empower
      nurses to act upon their intuitive feelings and obtain medical assistance in an
      early stage of deterioration. The aim of this systematic review is to identify
      the signs and symptoms that trigger nurses' worry or concern about a patient's
      condition. METHODS: We searched the databases PubMed, CINAHL, Psychinfo and
      Cochrane Library (Clinical Trials) using synonyms related to the three concepts:
      'nurses', 'worry/concern' and 'deterioration'. We included studies concerning
      adult patients on general wards in acute care hospitals. The search was performed
      from the start of the databases until 14 February 2014. RESULTS: The search
      resulted in 4,006 records, and 18 studies (five quantitative, nine qualitative
      and four mixed-methods designs) were included in the review. A total of 37 signs
      and symptoms reflecting the nature of the criterion worry or concern emerged from
      the data and were summarized in 10 general indicators. The results showed that
      worry or concern can be present with or without change in vital signs.
      CONCLUSIONS: The signs and symptoms we found in the literature reflect the nature
      of nurses' worry or concern, and nurses may incorporate these signs in their
      assessment of the patient and their decision to call for assistance. The fact
      that it is present before changes in vital signs suggests potential for improving
      care in an early stage of deterioration.

PMID- 25990250
TI  - Associations between metabolomic-identified changes of biomarkers and arterial
      stiffness in subjects progressing to impaired fasting glucose.
AB  - OBJECTIVE: We investigated correlations between age-related changes in
      circulating metabolites and arterial stiffness in impaired fasting glucose (IFG).
      DESIGN, SUBJECTS, MEASUREMENT: This prospective cohort study included 602
      healthy, normal fasting glucose (NFG) subjects (30-65 years old) who underwent
      triennial medical evaluation. After 3 years, 9.3% of subjects developed IFG (n =
      56). Age, gender, BMI and fasting glucose were used to match the remaining NFG
      subjects (n = 546) that were included for the control group (NFG group, n = 80).
      RESULTS: After 3 years, levels of fasting glucose, insulin and malondialdehyde,
      and brachial-ankle pulse wave velocity (baPWV) were significantly greater in the
      IFG group than in the NFG group after adjusting for baseline values. The IFG
      group had a greater increase in lactosylceramide (P = 0.001, q < 0.05) and a
      greater reduction in phosphatidylcholine (PC) (18:0/20:4) than the NFG group.
      Multiple linear regression analysis showed that the change in baPWV was
      independently and positively associated with changes in fasting glucose and
      lactosylceramide. In all subjects, lactosylceramide levels positively correlated
      with changes in baPWV and fasting glucose, while premenopausal women were not
      shown, and negatively correlated with changes in PC and LDL particle size.
      CONCLUSIONS: This study indicates that age-related increase in circulating
      lactosylceramide is an independent predictor of increased arterial stiffness in
      subjects with impaired fasting glucose.

PMID- 25990251
TI  - Identification and selective expansion of functionally superior T cells
      expressing chimeric antigen receptors.
AB  - BACKGROUND: T cells expressing chimeric antigen receptors (CARs) have shown
      exciting promise in cancer therapy, particularly in the treatment of B-cell
      malignancies. However, optimization of CAR-T cell production remains a trial-and
      error exercise due to a lack of phenotypic benchmarks that are clearly predictive
      of anti-tumor functionality. A close examination of the dynamic changes
      experienced by CAR-T cells upon stimulation can improve understanding of CAR-T
      cell biology and identify potential points for optimization in the production of
      highly functional T cells. METHODS: Primary human T cells expressing a second
      generation, anti-CD19 CAR were systematically examined for changes in phenotypic
      and functional responses to antigen exposure over time. Multi-color flow
      cytometry was performed to quantify dynamic changes in CAR-T cell viability,
      proliferation, as well as expression of various activation and exhaustion markers
      in response to varied antigen stimulation conditions. RESULTS: Stimulated CAR-T
      cells consistently bifurcate into two distinct subpopulations, only one of which
      (CAR(hi)/CD25(+)) exhibit anti-tumor functions. The use of central memory T cells
      as the starting population and the resilience-but not antigen density-of antigen
      presenting cells used to expand CAR-T cells were identified as critical
      parameters that augment the production of functionally superior T cells. We
      further demonstrate that the CAR(hi)/CD25(+) subpopulation upregulates PD-1 but
      is resistant to PD-L1-induced dysfunction. CONCLUSIONS: CAR-T cells expanded ex
      vivo for adoptive T-cell therapy undergo dynamic phenotypic changes during the
      expansion process and result in two distinct populations with dramatically
      different functional capacities. Significant and sustained CD25 and CAR
      expression upregulation is predictive of robust anti-tumor functionality in
      antigen-stimulated T cells, despite their correlation with persistent PD-1
      upregulation. The functionally superior subpopulation can be selectively
      augmented by careful calibration of antigen stimulation and the enrichment of
      central memory T-cell type.

PMID- 25990252
TI  - Susceptibility to echinocandins of Candida spp. strains isolated in Italy
      assessed by European Committee for Antimicrobial Susceptibility Testing and
      Clinical Laboratory Standards Institute broth microdilution methods.
AB  - BACKGROUND: The echinocandins are recommended as first-line therapy for Candida
      species infections, but drug resistance, especially among Candida glabrata, is
      becoming more frequent. We investigated the antifungal susceptibility of
      anidulafungin, caspofungin, and micafungin against 584 isolates of Candida spp.
      (bloodstream, other sterile sites) collected from patients admitted to an Italian
      university hospital between 2000 and 2013. The susceptibility was evaluated using
      the broth microdilution method according to both the European Committee for
      Antimicrobial Susceptibility Testing (EUCAST EDef 7.2) and the Clinical
      Laboratory Standards Institute (CLSI M27-A3). The echinocandin susceptibilities
      were assessed on the basis of the species-specific clinical breakpoints proposed
      by the EUCAST version 6.1 and CLSI M27-S4 documents. The two methods were
      comparable by assessing essential agreement (EA), categorical agreement (CA), and
      Spearman's correlation analysis (rho, r). RESULTS: The modal minimum inhibitory
      concentrations (MICs; MUg ? mL (-1)) values by both methods (EUCAST/CLSI) for
      anidulafungin, caspofungin, and micafungin for each species were, respectively,
      as follows: C. albicans, 0.03/0.12, 0.016/0.5, and 0.016/0.008; C. parapsilosis
      complex, 2/1, 2/2, and 2/1; C. tropicalis, 0.06/0.12, 0.06/0.12, and 0.06/0.12;
      C. glabrata complex, 0.03/0.25, 0.06/0.12, and 0.03/0.06; C. guilliermondii, 2/1,
      2/2, and 2/2; and C. krusei, 0.06/0.12, 0.12/0.5, and 0.06/0.12. The overall
      resistance rates for EUCAST/CLSI were as follows: anidulafungin, 2.5/0.9%;
      caspofungin, breakpoint not available/3.8%; micafungin, 2.7/1.5%. Candida
      glabrata complex was the least susceptible to all three echinocandins, and the
      percentages of resistant isolates by EUCAST/CLSI were as follows: anidulafungin,
      13.5/2.7%; caspofungin, breakpoint not available/16.2%; micafungin, 18.9/13.5%.
      The overall EA was 93 % for micafungin, 92% for anidulafungin, and 90% for
      caspofungin. The CA was >90% for all organism-drug combinations with the
      exception of C. glabrata and anidulafungin (89%). Spearman's rho for EUCAST/CLSI
      was 0.89 (p < 0.001) for caspofungin, 0.85 (p < 0.001) for anidulafungin, and
      0.83 for micafungin (p < 0.001). CONCLUSIONS: Independent of the procedure
      applied, no alarming resistance to the tested agents was found, although a
      reduced susceptibility was detected for C. glabrata complex. The EUCAST and CLSI
      methods produce similar MICs, indicating that using one method or the other
      should not result in susceptibilities different enough to affect treatment
      decisions.

PMID- 25990253
TI  - Telephone interview strategy can be used for screening inflammatory back pain in
      the community.
AB  - OBJECTIVE: Telephone surveys are less expensive and time-consuming for both
      interviewers and interviewees, with similar or even higher response rates than
      face-to-face interviews. In rheumatology, telephone technique has been used in a
      number of epidemiologic studies. In the present study, we conducted a telephone
      survey for screening inflammatory back pain (IBP) in the community. METHODS: One
      hundred and seventy-two patients with axial spondyloarthritis (axSpA) and 25
      patients with chronic mechanical back pain were included. A telephone interview
      and a face-to-face interview was conducted by the same physician using a
      standardized questionnaire that elicited information on all the components of IBP
      addressed in the Calin, Berlin and ASAS (the Assessment of SpondyloArthritis
      International Society) criteria sets. The telephone survey was repeated by
      another rheumatologist within the same week to assess the inter-rater agreement.
      RESULTS: Of 172 patients with axSpA, 114 could be classified as ankylosing
      spondylitis (AS) according to the modified New York criteria (AS group).The
      remaining 58 patients had active sacroiliitis on magnetic resonance imaging and
      they constituted the non-radiographic axSpA group (nr-axSpA group). Calin's
      criteria showed the highest sensitivity but also the lowest specificity with both
      interview methods. Calin's criteria showed the best agreement between the
      interview methods (kappa = 0.60). CONCLUSION: The results of our study indicate
      that telephone surveys based on Calin's criteria for IBP has a moderate, almost
      substantial agreement with face-to-face interviews and can be used as an easily
      applicable, less expensive and time-saving method in screening subjects for IBP.

PMID- 25990254
TI  - Exploration des cadres de construction des rampes d'accessibilite.
AB  - Accessibility to buildings promotes social participation through the application
      of inclusive design. However, architectural frameworks for constructing
      accessibility ramps are based on scant scientific evidence. This article presents
      a statement of established standards for construction criteria for accessibility
      ramps and makes recommendations from the perspective of inclusive design. A
      literature review was performed using the databases Medline, OTseeker, PsycINFO,
      and CINAHL (2000 to 2013), combining keywords referring to: universal
      accessibility, inclusive design, accessibility ramps, biomechanics, obesity, and
      disabilities. Non-scientific literature was also explored (e.g. building codes).
      The fifty-eight articles selected were grouped under five themes: 1) ramps and
      users; 2) materials and climate; 3) visual reference; 4) "wayfinding"; 5)
      durability, aesthetics and culture. Recommendations encouraging interdisciplinary
      practice, pegged to inclusive design, are exhibited (e.g. tracking, tilt,
      contrast).

PMID- 25990255
TI  - Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion
      in Older Men and Women: A Randomized Dose-Finding Trial.
AB  - The acid load accompanying modern diets may have adverse effects on bone and
      muscle metabolism. Treatment with alkaline salts of potassium can neutralize the
      acid load, but the optimal amount of alkali is not established. Our objective was
      to determine the effectiveness of two doses of potassium bicarbonate (KHCO3 )
      compared with placebo on biochemical markers of bone turnover, and calcium and
      nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled
      study, 244 men and women age 50 years and older were randomized to placebo or 1
      mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The
      primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N;
      changes in these measures were compared across the treatment groups. Exploratory
      outcomes included 24-hour urinary calcium excretion, serum amino-terminal
      propeptide of type I procollagen (P1NP), and muscle strength and function
      assessments. The median administered doses in the low-dose and high-dose groups
      were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo,
      urinary NTX declined significantly in the low-dose group (p = 0.012, after
      adjustment for baseline NTX, gender, and change in urine creatinine) and serum
      P1NP declined significantly in the low-dose group (p = 0.004, adjusted for
      baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3
      groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender,
      and changes in urine creatinine and calcium intake). There was no significant
      effect of either dose of KHCO3 on urinary N excretion or on the physical strength
      and function measures. KHCO3 has favorable effects on bone turnover and calcium
      excretion and the lower dose appears to be the more effective dose. Long-term
      trials to assess the effect of alkali on bone mass and fracture risk are needed.

PMID- 25990256
TI  - Factors Correlated to Protective and Risk Dietary Patterns in Immigrant Latino
      Mothers in Non-metropolitan Rural Communities.
AB  - Immigrant Latinos face conditions which over time negatively impact their
      nutritional behaviors and health outcomes. Our objective was to evaluate
      associations between environmental and lifestyle factors and both protective
      dietary patterns (e.g., intake of fruits and vegetables) and harmful dietary
      patterns (e.g., consumption of salty snacks and fast food). Surveys were
      individually and orally administered to 105 foreign-born Latina mothers living in
      rural locations in a Midwestern state. Principal component analysis created
      composite variables for each construct and Spearman correlations were conducted
      to determine associations. Protective dietary patterns were positively associated
      with access to food and information (rhos = 0.21) and language acculturation
      (rhos = 0.24), and negatively associated with family challenges (rhos = -0.31).
      Food insecurity was negatively associated with harmful dietary patterns (rhos = 
      0.24). Findings suggest that rural Latino dietary interventions should be
      complemented with comprehensive strategies addressing environmental and lifestyle
      factors across ecological domains.

PMID- 25990258
TI  - Improving antipsychotic prescribing practices in nursing facilities: The role of
      surveyor methods and surveying agencies in upholding the Nursing Home Reform Act.
AB  - BACKGROUND: Inappropriate prescribing of antipsychotics is a longstanding
      challenge to providing high quality care in nursing facilities. The 1987 Nursing
      Home Reform Act (NHRA) had an initial impact in reducing inappropriate
      prescribing, but rates returned to pre-NHRA levels. While the recent Partnership
      to Improve Dementia Care in Nursing Homes (Partnership) initiative has been
      successful in reducing the prescribing of antipsychotics in skilled nursing
      facilities/nursing facilities (NF), it is not known how this guidance initiative
      impacted prescribing practices and other care processes concerning NF residents
      with dementia. OBJECTIVES: The objectives of this study were to explore surveyor
      observations of NF care practices subsequent to participation the Partnership
      guidance program and to use a social ecological framework to estimate how these
      observations were influenced by individual, organizational, and contextual
      factors. METHODS: A total of 320 NF surveyors responded to a 49-item
      questionnaire designed in collaboration with CMS officials and state surveying
      agency personnel, and distributed by state agency directors. Three outcome
      variables: measuring improvements in clinical care, deficiencies in clinical
      care, and falsification of records in response to the Partnership initiative,
      were created from survey responses. A four-level social ecological framework
      describing the NF surveyor's environment was used to identify potential
      influences on surveyors' care observations. Logistic regression was used to
      evaluate the relationship between environment and outcome variables. RESULTS:
      Surveyors observed both improvements in clinical care, including 80.6% reporting
      nursing facility providers responding to consultant pharmacists' recommendations,
      and deficits in clinical care in response to the Partnership initiative.
      Furthermore, 39.7% of surveyors observed a new, but false, diagnosis of psychosis
      (as defined by the surveyor). Surveyor characteristics and methods and surveying
      agency and culture were found to substantially impact the success of the
      Partnership initiative. The most distal level of the framework evaluated in this
      study, state contextual effects, was found not to impact care observations.
      CONCLUSIONS: There is substantial variation in surveyor observations of changes
      to clinical care in response to the Partnership guidance initiative. Further
      investigation is needed into the type and severity of falsification of records
      observed by nursing facility surveyors. When constructing interventions to care
      for residents in NFs, policymakers must consider the environment in which
      surveyors operate.

PMID- 25990257
TI  - Renal function improvement in liver transplant recipients after early everolimus
      conversion: A clinical practice cohort study in Spain.
AB  - A national, multicenter, retrospective study was conducted to assess the results
      obtained for liver transplant recipients with conversion to everolimus in daily
      practice. The study included 477 recipients (481 transplantations). Indications
      for conversion to everolimus were renal dysfunction (32.6% of cases),
      hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de
      novo malignancy (29.7%). The median time from transplantation to conversion to
      everolimus was 68.7 months for de novo malignancy, 23.8 months for renal
      dysfunction, and 7.1 months for HCC and other indications. During the first year
      of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD],
      2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after
      conversion. An everolimus monotherapy regimen was followed by 28.5% of patients
      at 12 months. Patients with renal dysfunction showed a glomerular filtration rate
      (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline
      mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months
      after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in
      renal function was higher in patients with early conversion (<1 year). Adverse
      events were the primary reason for discontinuation in 11.2% of cases. The
      probability of survival at 3 years after conversion to everolimus was 83.0%,
      71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups,
      respectively. Everolimus is a viable option for the treatment of renal
      dysfunction, and earlier conversion is associated with better recovery of renal
      function. Prospective studies are needed to confirm advantages in patients with
      malignancy.

PMID- 25990259
TI  - Nano-welding and junction formation in hydrogen titanate nanowires by low-energy
      nitrogen ion irradiation.
AB  - Crystalline hydrogen titanate (H2Ti3O7) nanowires were irradiated with N(+) ions
      of different energies and fluences. Scanning electron microscopy reveals that at
      relatively lower fluence the nanowires are bent and start to adhere strongly to
      one another as well as to the silicon substrate. At higher fluence, the nanowires
      show large-scale welding and form a network of mainly 'X' and 'Y' junctions.
      Transmission electron microscopy and Raman scattering studies confirm a high
      degree of amorphization of the nanowire surface after irradiation. We suggest
      that while ion-irradiation induced defect formation and dangling bonds may lead
      to chemical bonding between nanowires, the large scale nano-welding and junction
      network formation can be ascribed to localized surface melting due to heat spike.
      Our results demonstrate that low energy ion irradiation with suitable choice of
      fluence may provide an attractive route to the formation and manipulation of
      large-area nanowire-based devices. 

PMID- 25990260
TI  - Comparing 1470- and 980-nm diode lasers for endovenous ablation treatments.
AB  - The purpose of this study was to compare the effectiveness of 1470- and 980-nm
      lasers with regard to power output, complications, recanalization rates, and
      treatment response. We prospectively evaluated the effectiveness of endovenous
      laser ablation (EVLA) in a total of 152 great and small saphenous veins from 96
      patients. Lasers were randomly used based on the availability of the units.
      Patients were clinically evaluated for Clinical Etiologic Anatomic
      Pathophysiologic (CEAP) stage and examined with Doppler ultrasound. Treatment
      response was determined anatomically by occlusion of the vein and clinically by
      the change in the venous clinical severity score (VCSS). Seventy-eight of the
      saphenous veins underwent EVLA with a 980-nm laser and 74 underwent EVLA with a
      1470-nm laser. Treatment response was (68) 87.2 % in the 980-nm group and (74)
      100 % in the 1470-nm group (p = 0.004). The median VCSS decreased from 4 to 2 in
      the 980-nm group (p < 0.001) and from 8 to 2 (p < 0.001) in the 1470-nm group. At
      1-year follow-up, seven veins treated with 980 nm and two veins treated with 1470
      nm were recanalized (p = 0.16); the average linear endovenous energy density
      (LEED) was 83.9 (r, 55-100) J/cm and 58.5 (r, 45-115) J/cm, respectively (p <
      0.001). Postoperative minor complications occurred in 23 (29.4 %) limbs in the
      980-nm group and in 19 (25.6 %) limbs of the 1470-nm group (p = 0.73). EVLA with
      the 1470-nm laser have less energy deposition for occlusion and better treatment
      response. 

PMID- 25990261
TI  - Comparison of conventional ROTEM(r) cups and pins to the ROTEM(r) cup and pin
      mini measuring cells (MiniCup).
AB  - BACKGROUND: Thromboelastometry (ROTEM(r)) is a well-established measurement to
      guide perioperative coagulation management. Recently, an enhancement for low
      volume specimens using cup and pin mini measuring cells (MiniCup) was invented
      for scientific non-clinical use. The MiniCup measuring cells allow testing with
      half of the blood volume required to run a test as compared to the conventional
      ROTEM(r) cup and pin (150 MUL vs. 300 MUL per assay). OBJECTIVES: The aim of this
      prospective study was to compare ROTEM(r) results using conventional cups and
      pins to the results of the MiniCup measuring cells. METHODS: Blood samples drawn
      during major pediatric surgery were analyzed using the conventional ROTEM(r) and
      the MiniCup system to compare parameters from the EXTEM, INTEM and FIBTEM assays.
      RESULTS: Citrated blood samples (n = 120) from 70 pediatric patients were
      analyzed. Results of the MiniCup cells were considerably different than the
      conventional ROTEM(r) cups and pins measurements. The MiniCup results show less
      clot firmness and demonstrate higher variability in the parameters reflecting the
      kinetics of clot building. CONCLUSION: The MiniCup measuring cells may offer
      advantages in pediatric care or research facilities, but specific reference
      ranges need to be established first, and adequate reproducibility must be
      determined by further studies before clinical use can be recommended.

PMID- 25990262
TI  - Development of novel dental adhesive with double benefits of protein-repellent
      and antibacterial capabilities.
AB  - OBJECTIVES: Secondary caries at the tooth-restoration margins remains a main
      reason for restoration failure. The objectives of this study were to: (1) combine
      protein-repellent 2-methacryloyloxyethyl phosphorylcholine (MPC) with quaternary
      ammonium dimethylaminohexadecyl methacrylate (DMAHDM) to develop a new dental
      adhesive with double benefits of protein-repellent and antibacterial capabilities
      for the first time; and (2) investigate the effects on protein adsorption, anti
      biofilm activity, and dentin bond strength. METHODS: MPC and DMAHDM were
      incorporated into Scotchbond Multi-Purpose (SBMP) primer and adhesive. Dentin
      shear bond strengths were measured using extracted human molars. Protein
      adsorption onto the adhesive resin surfaces was determined by the micro
      bicinchoninic acid (BCA) method. A dental plaque microcosm biofilm model with
      human saliva as inoculum was used to investigate biofilm metabolic activity,
      colony-forming unit (CFU) counts, lactic acid production and live/dead staining
      of biofilms on resins. RESULTS: Incorporation of 7.5% MPC and 5% DMAHDM into
      primer and adhesive did not adversely affect the dentin shear bond strength
      (p>0.1). The resin with 7.5% MPC+5% DMAHDM had protein adsorption that was nearly
      20-fold less than SBMP control (p<0.05). The resin with 7.5% MPC+5% DMAHDM had
      much stronger antibacterial effects than using MPC or DMAHDM alone (p<0.05).
      Biofilm CFU counts on the resin with 7.5% MPC+5% DMAHDM were reduced by more than
      4 orders of magnitude, compared to SBMP control. SIGNIFICANCE: The use of double
      agents (protein-repellent MPC+antibacterial DMAHDM) in dental adhesive achieved
      much stronger inhibition of biofilms than using each agent alone. The novel
      protein-repellent and antibacterial bonding agent is promising to reduce
      biofilm/plaque buildup and reduce recurrent caries at the tooth-restoration
      margins.

PMID- 25990263
TI  - Low-Temperature Preparation of Ag-Doped ZnO Nanowire Arrays, DFT Study, and
      Application to Light-Emitting Diode.
AB  - Doping ZnO nanowires (NWs) by group IB elements is an important challenge for
      integrating nanostructures into functional devices with better and tuned
      performances. The growth of Ag-doped ZnO NWs by electrodeposition at 90  degrees
      C using a chloride bath and molecular oxygen precursor is reported. Ag acts as an
      electrocatalyst for the deposition and influences the nucleation and growth of
      the structures. The silver atomic concentration in the wires is controlled by the
      additive concentration in the deposition bath and a content up to 3.7 atomic % is
      reported. XRD analysis shows that the integration of silver enlarges the lattice
      parameters of ZnO. The optical measurements also show that the direct optical
      bandgap of ZnO is reduced by silver doping. The bandgap shift and lattice
      expansion are explained by first principle calculations using the density
      functional theory (DFT) on the silver impurity integration as an interstitial
      (Ag(i)) and as a substitute of zinc atom (Ag(Zn)) in the crystal lattice. They
      notably indicate that Ag(Zn) doping forms an impurity band because of Ag 4d and O
      2p orbital interactions, shifting the Fermi level toward the valence band. At
      least, Ag-doped ZnO vertically aligned nanowire arrays have been epitaxially
      grown on GaN(001) substrate. The heterostructure has been inserted in a light
      emitting device. UV-blue light emission has been achieved with a low emission
      threshold of 5 V and a tunable red-shifted emission spectrum related to the
      bandgap reduction induced by silver doping of the ZnO emitter material.

PMID- 25990264
TI  - [Clinical development of the automatic implantable defibrillator over 35 years: A
      success story].
AB  - After 12 years of development and experimental evaluation, the first automatic
      implantable cardioverter-defibrillator (ICD) was implanted in man on February 4,
      1980. This overview describes the technical and functional developments over 35
      years from a simple shock-box, weighing 292 g, to the sophisticated 80 g device
      of today, delivering graded therapy to sustained ventricular arrhythmias and
      biventricular stimulation to treat heart failure. Finally, a special tribute is
      given to Michel Mirowski, one of the inventors of the ICD, as scientist and
      physician dedicated to patient care.

PMID- 25990265
TI  - [Right ventricular outflow tract tachycardia 30 years after surgical correction
      of tetralogy of Fallot].
AB  - This case report describes a 31-year-old man with a sustained wide complex
      tachycardia with left bundle brunch block morphology after surgical repair of a
      tetralogy of Fallot. The tachycardia was inducible after orciprenaline
      administration after ventricular stimulation with one extra beat. In combination
      with the three-dimensional electroanatomic mapping system and pace mapping
      technique the origin of the tachycardia was identified at the lateral free wall
      of the right ventricular outflow tract tachycardia (RVOT) inferior of the
      pulmonary valve. Successful radiofrequency ablation was performed and the patient
      is still free from ventricular tachycardia. 

PMID- 25990266
TI  - Speckle-Tracking Strain Imaging Identifies Alterations in Left Atrial Mechanics
      With General Anesthesia and Positive-Pressure Ventilation.
AB  - OBJECTIVES: The primary aim of this study was to use speckle-tracking strain
      imaging to evaluate the effect of general anesthesia (GA) and positive-pressure
      ventilation (PPV) on left atrial (LA) mechanics. The authors hypothesized that GA
      and PPV would be associated with a decrease in LA strain. The secondary aims were
      to investigate the effects of GA and PPV on traditional Doppler-derived measures
      of LA function and Doppler echocardiographic grade of diastolic function. DESIGN:
      A prospective observational study. SETTING: A university hospital. PARTICIPANTS:
      Adult patients undergoing cardiac surgery. INTERVENTIONS: Transthoracic
      echocardiography was performed at baseline and under GA with PPV. MEASUREMENTS
      AND MAIN RESULTS: Changes in LA function associated with GA and PPV were assessed
      using LA speckle-tracking strain imaging. A reduction was observed in LA peak
      longitudinal strain (24% v 18%, p<0.001) and preatrial contraction strain (13% v
      8%, p<0.001). No difference was seen in LA contraction strain or atrial ejection
      fraction. Indexed LA volume and Doppler diastolic indices also were reduced
      significantly, and 39% of patients had a change in measured diastolic grade under
      GA with PPV. CONCLUSIONS: Speckle-tracking strain imaging of the left atrium
      demonstrated that GA and PPV had a significant impact on LA mechanics by
      decreasing strain measures of LA preload, with a lesser effect on LA
      contractility.

PMID- 25990267
TI  - Management of LVAD Patients for Noncardiac Surgery: A Single-Institution Study.
AB  - OBJECTIVE: To describe the experience regarding the perioperative management of
      patients with left ventricular assist devices (LVADs) who require anesthesia
      while undergoing noncardiac surgery (NCS) at a single medical center. DESIGN:
      Retrospective chart review SETTING: Academic medical center PARTICIPANTS:
      Patients with LVADs INTERVENTIONS: Medical records from April 1, 2009 through
      January 31, 2014 were reviewed for patients who underwent Heartmate II LVAD
      placement at this facility. Individual records were reviewed for NCS after LVAD
      placement, specifically investigating perioperative and anesthetic management.
      MEASUREMENTS AND MAIN RESULTS: Seventy-one patients underwent LVAD placement
      during this time period. Thirty-five patients (49%) underwent a total of 101 NCS
      procedures. Arterial catheters were placed in 19 patients (19%), and 33 patients
      (33%) were intubated for their procedure. No complications or perioperative
      mortality occurred related to the NCS. CONCLUSIONS: Noncardiac surgery is
      becoming more common in patients with LVADs. Anesthetic management of these
      patients outside of the cardiac operating room is limited. Patients with
      Heartmate II LVADs can safely undergo noncardiac surgery.

PMID- 25990268
TI  - Low Circulating Levels of Growth Differentiation Factor-15 Before Coronary Artery
      Bypass Surgery May Predict Postoperative Atrial Fibrillation.
AB  - OBJECTIVES: To assess the role of growth differentiation factor-15 (GDF-15) as a
      potential new predictor of postoperative atrial fibrillation (POAF) after off
      pump (OFP) and on-pump (ONP) coronary artery bypass graft (CABG) surgery. DESIGN:
      Prospective, single-center, observational study. SETTING: University teaching
      hospital. PARTICIPANTS: The first 50 patients planned for OFP surgery and the
      first 50 patients planned for ONP surgery among patients referred for CABG with
      the following exclusion criteria: age<18 or>80 years, previous atrial
      fibrillation/flutter, previous treatment with amiodarone, previous cardiac
      surgery, and emergency surgery. INTERVENTIONS: Included patients were equipped
      with long-duration (7 days) Holter-ECG monitoring. MEASUREMENTS AND MAIN RESULTS:
      POAF was defined as an AF episode lasting>30 seconds. All patients underwent
      preoperative echocardiography to assess left ventricular ejection fraction and
      left atrial diameter. GDF-15 levels were assessed after induction of anesthesia
      and 12 hours after arrival at the intensive care unit. Among the 100 patients, 34
      (34%) developed POAF. In Cox multivariate regression analysis, the EuroSCORE,
      left atrial diameter>45 mm, and low GDF-15 levels at induction were associated
      independently with the onset of POAF. In contrast, preoperative NT-proBNP levels
      did not predict POAF. The use of ONP surgery was not associated with a higher
      incidence of POAF, even though baseline and follow-up characteristics in ONP and
      OFP patients were identical. CONCLUSIONS: In patients with no history of AF, a
      low plasma level of GDF-15 before CABG surgery was a strong independent predictor
      of POAF. Moreover, preoperative plasma GDF-15 levels added an incremental
      predictive value to classic risk factors of POAF.

PMID- 25990269
TI  - Establishment and characterization of fin-derived cell line from ornamental carp,
      Cyprinus carpio koi, for virus isolation in India.
AB  - Cyprinus carpio koi fin (CCKF) cell line was established and characterized from
      the caudal fin tissue of ornamental common carp, C. carpio koi. This cell line
      has been maintained in L-15 medium supplemented with 15% foetal bovine serum
      (FBS) and subcultured more than 52 times over a period of 24 mo. The CCKF cell
      line consisted of epithelial cells and was able to grow at temperatures between
      22 and 35 degrees C with an optimum temperature of 28 degrees C. The growth rate
      of these cells increased as the proportion of FBS increased from 2 to 20% with
      optimum growth at the concentrations of 15% FBS. Karyotype analysis revealed that
      the modal chromosome number of CCKF cells was 2n = 100. Partial amplification and
      sequencing of fragments of two mitochondrial genes 16S rRNA and COI confirmed
      that CCKF cell line originated from ornamental common carp. The CCKF cells showed
      strong reaction to the cytokeratin marker, indicating that it was epithelial in
      nature. The extracellular products of Vibrio cholerae MTCC 3904 and Aeromonas
      hydrophila were toxic to the CCKF cells and not susceptible to viral nervous
      necrosis virus (VNNV). These CCKF cells were confirmed for the absence of
      Mycoplasma sp. by polymerase chain reaction. Furthermore, 90% of viable cells
      could be effectively revived 4 mo after cryopreservation from CCKF cell
      population suggesting the possibility of long-term storage of the cells.

PMID- 25990270
TI  - Upregulation of miR-197 inhibits cell proliferation by directly targeting IGFBP5
      in human uterine leiomyoma cells.
AB  - Uterine leiomyoma (ULM), one of the most common reproductive tract neoplasms in
      premenopausal women, is a kind of benign tumor with multigene involved. Finding
      and studying the key gene involved has been a long-needed factor for developing
      non-surgery therapy and prevention methods. The dysregulated microRNAs were
      reported to play important roles in ULM pathobiology by regulating tumor growth.
      Our investigations have revealed that miR-197 is at low expression in ULM.
      Characterization of the effects of miR-197 in ULM demonstrated that
      downregulation of miR-197 increased cell growth and induced cell cycle arrest in
      the G0/G1 phase in vitro, while upregulation of miR-197 expression had the
      opposite effect on ULM growth and progression. Further research on the mechanism
      of miR-197 on the proliferation of ULM cells, we showed that miR-197 inhibited
      cell proliferation of ULM by directly targeting IGFBP5, which was overexpressed
      in ULM and played an important role in the etiology of ULM. These findings
      obtained in this study deliver insights and further expand our understanding of
      the role of miR-197 and its target IGFBP5 in ULM development, which provides a
      potential novel therapeutic agent to target the proliferation of ULM cells. 

PMID- 25990271
TI  - Deoxycholic acid inhibited proliferation and induced apoptosis and necrosis by
      regulating the activity of transcription factors in rat pancreatic acinar cell
      line AR42J.
AB  - The objective of this study is to investigate the effect of deoxycholic acid
      (DCA) on rat pancreatic acinar cell line AR42J and the functional mechanisms of
      DCA on AR42J cells. AR42J cells were treated with various concentrations of DCA
      for 24 h and also treated with 0.4 mmol/L DCA for multiple times, and then, 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was
      performed to detect the AR42J cell survival rate. Flow cytometric was used to
      detect the cell apoptosis and necrosis in AR42J cells treated with 0.4 mmol/L and
      0.8 mmol/L DCA. The cells treated with phosphate buffer saline (PBS) were served
      as control. In addition, the DNA-binding activity assays of transcription factors
      (TFs) in nuclear proteins of cells treated with DCA were determined using
      Panomics Procarta Transcription Factor Assay Kit. The relative survival rates
      were markedly decreased (P < 0.05) in a dose- and time-dependent manner. Compared
      with control group, the cell apoptosis and necrosis ratio were both significantly
      elevated in 0.4 mmol/L DCA and 0.8 mmol/L DCA groups (P < 0.01). A significant
      increase (P < 0.05) in the activity of transcription factor 2 (ATF2), interferon
      stimulated response element (ISRE), NKX-2.5, androgen receptor (AR), p53, and
      hypoxia-inducible factor-1 (HIF-1) was observed, and the activity of peroxisome
      proliferator-activated receptor (PPAR), activator protein 1 (AP1), and E2F1 was
      reduced (P < 0.05). In conclusion, DCA inhibited proliferation and induced
      apoptosis and necrosis in AR42J cells. The expression changes of related genes
      regulated by TFs might be the molecular mechanism of AR42J cell injury.

PMID- 25990272
TI  - Ethical Issues in Surgical Critical Care: The Complexity of Interpersonal
      Relationships in the Surgical Intensive Care Unit.
AB  - A major challenge in the era of shared medical decision making is the navigation
      of complex relationships between the physicians, patients, and surrogates who
      guide treatment plans for critically ill patients. This review of ethical issues
      in adult surgical critical care explores factors influencing interactions among
      the characters most prominently involved in health care decisions in the surgical
      intensive care unit: the patient, the surrogate, the surgeon, and the
      intensivist. Ethical tensions in the surgeon-patient relationship in the elective
      setting may arise from the preoperative surgical covenant and the development of
      surgical complications. Unlike that of the surgeon, the intensivist's
      relationship with the individual patient must be balanced with the need to serve
      other acutely ill patients. Due to their unique perspectives, surgeons and
      intensivists may disagree about decisions to pursue life-sustaining therapies for
      critically ill postoperative patients. Finally, although surrogates are asked to
      make decisions for patients on the basis of the substituted judgment or best
      interest standards, these models may underestimate the nuances of postoperative
      surrogate decision making. Strategies to minimize conflicts regarding treatment
      decisions are centered on early, honest, and consistent communication between all
      parties. 

PMID- 25990273
TI  - Viral Respiratory Infections of Adults in the Intensive Care Unit.
AB  - Viral lower respiratory tract infections (LRTIs) are an underappreciated cause of
      critical illness in adults. Recent advances in viral detection techniques over
      the past decade have demonstrated viral LRTIs are associated with rates of
      morbidity, mortality, and health care utilization comparable to those of seen
      with bacterial community acquired and nosocomial pneumonias. In this review, we
      describe the relationship between viral LRTIs and critical illness, as well as
      discuss relevant clinical features and management strategies for the more
      prevalent respiratory viral pathogens. 

PMID- 25990274
TI  - Intimal thickening of peripheral pulmonary vein: Analysis of 139 consecutive
      autopsy cases.
AB  - Intimal thickening of the peripheral pulmonary veins collected from 139 autopsy
      cases (ages ranging from 1 to 96 years) was examined morphologically. The
      peripheral pulmonary veins were classified as medium-sized veins, small veins,
      and postcapillary venules. Intimal thickening, graded into four levels from (-)
      to (+++), increased with age in all three types of the peripheral veins. The
      severity of intimal thickening was age-dependent. In mediumsized veins, smooth
      muscle cells were recognized in the intima of all ages, though the amount of
      collagen fiber in the intima increased with age. In small veins, slight fibrosis
      and a few smooth muscle cells were seen in the subendothelial regions in autopsy
      cases up to 20 years of age. Thereafter, collagenous thickening was common. In
      postcapillary venules, edematous or dense collagenous thickening was a common
      feature of the intimal thickening in the autopsy cases over 20 years old. In
      those between 1 and 20 years of age who succumbed to left ventricular failure,
      intimal thickening was more severe than in those of the same age range in this
      study. The pathogenesis and the clinical significance of age-associated intimal
      thickening of the pulmonary veins has not been elucidated yet. 

PMID- 25990275
TI  - Cardiac transplant-associated vascular disease: Evolution, immunophenotype, and
      evidence of endothelial activation.
AB  - Transplant-associated vascular disease (TAVD) is a major cause of late mortality
      after cardiac transplantation. To elucidate the evolution of TAVD, the autopsy
      histopathology of five cardiac allograft recipients who died >=12 months
      posttransplantation was studied semiquantitatively. Vessel cross sections were
      analyzed for size, proliferative lesions, inflammation, lipid, and thrombi. The
      type of inflammatory cells in the vessels were characterized by
      immunohistochemistry, and the activation state of the vessel endothelium was
      characterized by immunohistochemistry for HLA-DR and inducible endothelial
      leukocyte adhesion proteins [endothelial leukocyte adhesion molecule-1 (SLAM-1)
      and vascular cell adhesion molecule-1 (VCAM-1)]. The mean posttransplantation
      interval was 27.2 months (range 12-40). TAVD was present in all five patients and
      was the cause of death in four of five. The percentage of vessels with
      proliferative lesions increased progressively with the duration of survival after
      transplantation. Both arteries and veins contained proliferative lesions, but
      more arteries than veins were involved at all time points. Large veins and large
      arteries had a significantly higher proportion of proliferative lesions than
      small veins (p < 0.04) and small arteries (p < 0.06), respectively. Inflammatory
      lesions were more prevalent in arteries than veins, 55.7% versus 10.9% (p <
      0.001). The inflammatory vascular lesions were comprised principally of T
      lymphocytes, with smaller numbers of B lymphocytes and macrophages. The
      endothelium of arteries and veins expressed HLA-DR as well as VCAM-1, but stains
      for ELAM-1 showed only focal expression. By linear regression, intimal/medial
      inflammation decreased with time (r = -0.81, p < 0.06) and adventitial
      inflammation increased with time (r = +0.98, p < 0.001). Lipid-containing lesions
      were observed in 13.0% of arterial cross sections and were not seen in veins.
      Lipid containing arterial lesions increased progressively with both time and
      vessel size, but, in contrast to proliferative and inflammatory lesions, were not
      seen at any time interval in veins or small arteries. In summary, TAVD is an
      inflammatory and proliferative process that involves arteries more than veins,
      and is more prevalent in large vessels and at greater posttransplantation
      intervals. Vascular T cell inflammation, intimal proliferation, and an activated
      endothelial cell phenotype appear to be closely related in the development of
      TAVD. 

PMID- 25990276
TI  - Accumulation of indium-111-labeled human low density lipoprotein in the rabbit
      aorta: Implications for nuclear imaging of vascular lesions.
AB  - Nuclear imaging of atheromata must distinguish lesions from both blood pool and
      normal arterial tissue. We have examined spatial and temporal variations of
      indium-111-labeled human low density lipoprotein (LDL) accumulation in rabbit
      aortas. LDL-derived In-111 activity was time-independent in lesion-resistant
      regions of aortas from normal and hypercholesterolemic animals (mean 2.9 * 10(-6)
      percent injected activity per milligram tissue [%IA/mg]) and in lesion-prone
      regions of normal aortas (mean 7.1 * 10(-6) %IA/mg). In contrast, activity in
      sudanophilic lesions of hypercholesterolemic rabbit aortas reached a peak of 31 *
      10(-6) %IA/mg at 92 hours postinjection. The mean ratio between activity in
      lesions versus lesion-resistant regions described a broad convex curve with
      minima of 4:1 at 14 hours and 136 hours and a peak of 14:1 measured at 72 hours
      postinjection. The mean ratio between In-111 in lesions and blood followed a
      sigmoid curve, rising exponentially from 1:25 at 14 hours to 1:3 by 72 hours
      postinjection. We conclude that optimal signal-to-noise ratios for monitoring
      atheroma-associated LDL-derived radioactivity occur late, not before about 3 days
      postinjection. Therefore, LDL labeled with In-111 or even longer-lived
      radionuclides holds the greatest promise for effective clinical nuclear imaging
      of atherosclerosis. 

PMID- 25990277
TI  - Pathogenesis of a double rupture (septal and free wall rupture) after acute
      myocardial infarction.
AB  - Rupture of both the ventricular septum and free wall (double rupture) is an
      unusual and, typically fatal, post-myocardial infarction complication. We report
      here the sequence of events leading to the formation of a double rupture. 

PMID- 25990278
TI  - Branch location in the left anterior descending coronary artery and its relation
      to the known distribution of early atherosclerosis.
AB  - The circumferential and longitudinal locations of branches were determined for 33
      left anterior descending coronary arteries (LADS) from persons aged less than 40
      years who had died of noncardiovascular causes. In 17, branch location was
      determined using digitized maps of opened perfusion fixed arteries. In the
      remainder branch location was measured directly from resin casts of the arteries.
      Branch location showed a fairly uniform longitudinal distribution throughout the
      LAD. In the proximal 3 cm of the LAD-the segment known to be principally involved
      in early atherosclerosis-the results indicate symmetrical distribution of
      branches, with origins from the posterior and, particularly, both lateral walls.
      This is in sharp contrast to the known distribution of early atherosclerotic
      lesions in this area, which occur mainly on the side wall opposite the flow
      divider separating the circumflex. This study suggests that these branches are
      not an important determinant for location of atherosclerosis in this site. 

PMID- 25990279
TI  - Further morphological observations on hearts with twisted atrioventricular
      connections (criss-cross hearts).
AB  - A superior and anterior location of the tricuspid valve in the setting of
      malalignment between the atrial and ventricular septal structures was the
      characteristic unifying morphologic feature of seven autopsied hearts with
      twisted atrioventricular connections. The peculiar angiocardiographic appearances
      of this lesion could be readily explained by the findings of unusual recesses in
      the right atrium, in the right ventricle, and in the left ventricle. The recess
      in the morphologically left ventricle was seen in each case at the right
      posterior part (or, in the hearts with left-handed ventricles, at the left part)
      of the chamber. Displacement of the right-sided atrioventricular valve far from
      the inferior caval vein (vena cava) had produced the recess in the
      morphologically right atrium; this feature was most prominent in the heart in
      which the atrioventricular connections were discordant. The recess within the
      right ventricular outflow tract was seen in four hearts, in all of which the
      inlet and apical trabecular components of the right ventricle were hypoplastic. 

PMID- 25990280
TI  - Transcriptional regulation of calcium-activated neutral protease in
      cardiomyocytes of hypertensive rats.
AB  - Increased enzymatic activity of calcium-activated neutral protease II (CANP II)
      has been reported previously in cardiac tissues of rats with 2 kidney, 1 clip
      Goldblatt hypertension (2K, 1C-HT); this was associated with elevated
      intracellular free Ca(++). Because it was suggested that increased levels of the
      enzyme were responsible for the enhanced activity, CANP II mRNA expression was
      assessed in cardiomyocytes isolated from 2K, 1C-HT rats and from a genetic model
      of hypertension, the spontaneously hypertensive rat (SHR). Utilizing a rabbit
      probe for the large subunit of CANP II (pLM 1006 cDNA), a 3.7 kilobase mRNA band
      was visualized in Northern blots of poly A+ RNA. Densitometric analysis of the
      blots revealed that there was a significant (p < 0.005) increase in the levels of
      CANP II large subunit mRNA in cardiomyocytes of 2K, 1C-HT rats when compared with
      controls. Interestingly, CANP II mRNA levels were comparable in cardiomyocytes of
      SHR and Wistar Kyoto (WKY) rats. Results of nuclear runoff transcription assays
      indicated that enhanced expression of CANP II mRNA in 2K, 1C-HT rat hearts was
      regulated at the transcriptional level. The data support specific CANP II gene
      activation in the hearts of renal hypertensive rats. 

PMID- 25990281
TI  - Hypersensitivity myocarditis: Findings in native and transplanted hearts.
AB  - Seven explanted hearts from a total of 288 heart transplants performed at UCLA
      Medical Center had histologic evidence of hypersensitivity myocarditis
      (prevalence = 2.4%). Three patients had a clinical history of drug allergy, and
      two had a clinically documented drug reaction prior to transplant. Three patients
      had peripheral eosinophilia prior to transplant. Five patients with
      hypersensitivity myocarditis had dilated cardiomyopathy, one had congenital
      abnormalities, and one had ischemic heart disease. In the period up to 3 weeks
      posttransplant, four patients had episodes of acute rejection (ISHLT grade 2 to
      4) with eosinophils histologically. Results suggest that hypersensitivity
      myocarditis may have an increasing prevalence in the native heart before
      transplant and in the newly transplanted heart. 

PMID- 25990282
TI  - An historical review of rupture of the heart.
AB  - In 1649 William Harvey noted the autopsy findings of a patient with spontaneous
      rupture of the heart. Additional reports by Nicholls, Morgagni, Hodgson, Quain,
      Vulpian, and others describing the dramatic clinical and pathological features of
      cardiac rupture appeared during the following 250 years. These reports are cited
      in order to document and trace an increasing awareness that acute myocardial
      infarction caused by obstructive coronary artery disease was the most frequent
      cause of this catastrophic event. Frequently these older reports speak for
      themselves without elaboration. At other times, they will be cautiously
      interpreted in the context of present-day understanding of this disease. 

PMID- 25990283
TI  - Solvent Molding of Organic Morphologies Made of Supramolecular Chiral Polymers.
AB  - The self-assembly and self-organization behavior of uracil-conjugated enantiopure
      (R)- or (S)-1,1'-binaphthyl-2,2'-diol (BINOL) and a hydrophobic oligo(p-phenylene
      ethynylene) (OPE) chromophore exposing 2,6-di(acetylamino)pyridine termini are
      reported. Systematic spectroscopic (UV-vis, CD, fluorescence, NMR, and SAXS) and
      microscopic studies (TEM and AFM) showed that BINOL and OPE compounds undergo
      triple H-bonding recognition, generating different organic nanostructures in
      solution. Depending on the solvophobic properties of the liquid media (toluene,
      CHCl3, CHCl3/CHX, and CHX/THF), spherical, rod-like, fibrous, and helical
      morphologies were obtained, with the latter being the only nanostructures
      expressing chirality at the microscopic level. SAXS analysis combined with
      molecular modeling simulations showed that the helical superstructures are
      composed of dimeric double-cable tape-like structures that, in turn, are
      supercoiled at the microscale. This behavior is interpreted as a consequence of
      an interplay among the degree of association of the H-bonded recognition, the
      vapor pressure of the solvent, and the solvophobic/solvophilic character of the
      supramolecular adducts in the different solutions under static and dynamic
      conditions, namely solvent evaporation conditions at room temperature. 

PMID- 25990284
TI  - GmWRKY27 interacts with GmMYB174 to reduce expression of GmNAC29 for stress
      tolerance in soybean plants.
AB  - Soybean (Glycine max) is an important crop for oil and protein resources
      worldwide. The molecular mechanism of the abiotic stress response in soybean is
      largely unclear. We previously identified multiple stress-responsive WRKY genes
      from soybean. Here, we further characterized the roles of one of these genes,
      GmWRKY27, in abiotic stress tolerance using a transgenic hairy root assay.
      GmWRKY27 expression was increased by various abiotic stresses. Over-expression
      and RNAi analysis demonstrated that GmWRKY27 improves salt and drought tolerance
      in transgenic soybean hairy roots. Measurement of physiological parameters,
      including reactive oxygen species and proline contents, supported this
      conclusion. GmWRKY27 inhibits expression of a downstream gene GmNAC29 by binding
      to the W-boxes in its promoter region. The GmNAC29 is a negative factor of stress
      tolerance as indicated by the performance of transgenic hairy roots under stress.
      GmWRKY27 interacts with GmMYB174, which also suppresses GmNAC29 expression and
      enhances drought stress tolerance. The GmWRKY27 and GmMYB174 may have evolved to
      bind to neighbouring cis elements in the GmNAC29 promoter to co-reduce promoter
      activity and gene expression. Our study discloses a valuable mechanism in soybean
      for regulation of the stress response by two associated transcription factors.
      Manipulation of these genes should facilitate improvements in stress tolerance in
      soybean and other crops. 

PMID- 25990285
TI  - Human metabolic responses to chronic environmental polycyclic aromatic
      hydrocarbon exposure by a metabolomic approach.
AB  - The toxicities of polycyclic aromatic hydrocarbons (PAHs) have been extensively
      explored due to their carcinogenic and mutagenic potency; however, little is
      known about the metabolic responses to chronic environmental PAH exposure among
      the general population. In the present study, 566 healthy volunteers were
      dichotomized into exposed and control groups to investigate PAH-induced
      perturbations in the metabolic profiles. Nine urine PAH metabolites were measured
      by a sensitive LC-MS/MS method to comprehensively evaluate the PAH exposure level
      of each individual, and the metabolic profiles were characterized via a LC-MS
      based metabolomic approach. PAH exposure was correlated to its metabolic outcomes
      by linear and logistic regression analyses. Metabolites related to amino acid,
      purine, lipid, and glucuronic acid metabolism were significantly changed in the
      exposed group. 1-Hydroxyphenanthrene and dodecadienylcarnitine have potential as
      sensitive and reliable biomarkers for PAH exposure and its metabolic outcomes,
      respectively, in the general population. These findings generally support the
      hypothesis that environmental PAH exposure causes oxidative stress-related
      effects in humans. The current study provides new insight into the early
      molecular events induced by PAH exposure in the actual environment. 

PMID- 25990286
TI  - The role of patch testing in the management of oral lichenoid reactions.
AB  - BACKGROUND AND OBJECTIVES: The distinction of oral lichenoid reactions from oral
      lichen planus may be difficult in a clinical setting. Our aims were to ascertain
      the utility of patch testing to confirm the association of oral lichenoid
      reactions with dental restorations and to identify the benefits of replacement of
      restorations, primarily made of amalgam. METHODS: Patients seen in an oral
      medicine unit over a 10-year period diagnosed with oral lichenoid reactions, with
      oral lichen planus resistant to treatment or with atypical lichenoid features
      were included in this study. All had been subjected to skin patch testing.
      Histopathology reports blinded to patch test results were scrutinized. Patch-test
      positive subjects were advised to have their restorations replaced. All were
      followed up to determine disease resolution for at least 3 months thereafter.
      RESULTS: Among 115 patients, 67.8% patients reacted positive to a dental material
      and nearly a quarter to mercury or amalgam. No correlation was found between
      pathology and skin patch testing results (P = 0.44). A total of 87 patients were
      followed up in clinic, and among 26 patch-test-positive patients who had their
      amalgam fillings replaced, moderate to complete resolution was noted in 81%.
      CONCLUSIONS: Skin patch testing is a valuable tool to confirm clinically
      suspected oral lichenoid reactions. Pathology diagnoses of oral lichenoid
      reactions did not correlate with patch test results. Prospective studies are
      needed to ascertain that a clinically suspected oral lichenoid reaction with a
      positive patch test result may resolve after the replacement of amalgam fillings.

PMID- 25990287
TI  - Variation in serotonin transporter linked polymorphic region (5-HTTLPR)
      short/long genotype modulates resting frontal electroencephalography asymmetries
      in children.
AB  - Previous studies have documented the serotonin transporter linked polymorphic
      region (5-HTTLPR) as a genetic susceptibility variant that contributes to
      variability in outcomes related to affective psychopathology, with the short
      allele associated with negative affectivity and the long allele associated with
      positive affectivity. In a separate but related line of research, extensive
      evidence suggests that frontal electroencephalography (EEG) hemispheric asymmetry
      in the alpha band is also associated with risk for affective psychopathologies,
      with leftward asymmetry associated with approach-related behavior patterns and
      rightward frontal EEG asymmetry associated with withdrawn behavioral tendencies.
      We examined frontal EEG hemispheric asymmetries in relation to 5-HTTLPR
      genotyping in 70 children between 4 and 6 years of age. Analyses revealed that
      frontal EEG lateralization interacted with genotype such that children homozygous
      for the short allele exhibited rightward frontal EEG asymmetries, children who
      were homozygous for the long allele consistently exhibited a positive pattern of
      leftward asymmetry, and heterozygotes exhibited equivalent left and right frontal
      activity. These findings suggest that the 5-HTTLPR short allele may provide a
      degree of susceptibility for later affective psychopathology in adolescence and
      adulthood, through mediation of frontal brain activity that is associated with
      cognitive-behavioral withdrawal tendencies and negative affectivity. 

PMID- 25990288
TI  - Development of an ASAS-endorsed recommendation for the early referral of patients
      with a suspicion of axial spondyloarthritis.
AB  - The aim of this work was to develop a consensual recommendation under the
      auspices of the Assessment of SpondyloArthritis international Society (ASAS) for
      early referral of patients with a suspicion of axial spondyloarthritis by non
      rheumatologists. The development of a referral recommendation consisted of four
      phases: (1) systematic literature review, (2) the first Delphi round aiming at
      identification of unmet needs and development of a candidate list of referral
      parameters, (3) the second Delphi round aiming at identification of the most
      useful combination of referral parameters and (4) final discussion and formal
      endorsement by ASAS membership. The following consensus on a referral
      recommendation was achieved as a result of the Delphi processes and final voting:
      "Patients with chronic back pain (duration >=3 months) and back pain onset before
      45 years of age should be referred to a rheumatologist if at least one of the
      following parameters is present: Inflammatory back pain; human leucocyte antigen
      B27; Sacroiliitis on imaging if available (X-rays or magnetic resonance imaging);
      Peripheral manifestations (arthritis, enthesitis, dactylitis); Extra-articular
      manifestations (psoriasis, inflammatory bowel disease, uveitis); Positive family
      history for spondyloarthritis; Good response to non-steroidal anti-inflammatory
      drugs; Elevated acute phase reactant." A consensual ASAS-endorsed referral
      recommendation for patients suspected of having axial spondyloarthritis was
      developed as a flexible and universal strategy to be used in clinical practice by
      primary care physicians or non-rheumatology specialists. The practical value of
      this strategy applied in different settings should be determined in future
      studies. 

PMID- 25990289
TI  - A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.
AB  - OBJECTIVE: Copy number variants (CNVs) have been associated with the risk to
      develop multiple autoimmune diseases. Our objective was to identify CNVs
      associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide
      analysis approach. METHODS: A total of 835 patients with PsA and 1498 healthy
      controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip
      genotyping platform. Genomic CNVs were characterised using CNstream analysis
      software and analysed for association using the chi(2) test. The most significant
      genomic CNV associations with PsA risk were independently tested in a validation
      sample of 1133 patients with PsA and 1831 healthy controls. In order to test for
      the specificity of the variants with PsA aetiology, we also analysed the
      association to a cohort of 822 patients with purely cutaneous psoriasis (PsC).
      RESULTS: A total of 165 common CNVs were identified in the genome-wide analysis.
      We found a highly significant association of an intergenic deletion between
      ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent
      patient and control cohort, we validated the association between ADAMTS9-MAGI1
      deletion and PsA risk (p=0.032). Using next-generation sequencing, we
      characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we
      found a lower frequency of the deletion compared with the PsA cohort (p=0.0088)
      and a similar frequency to that of healthy controls (p>0.3). CONCLUSIONS: The
      present genome-wide scan for CNVs associated with PsA risk has identified a new
      deletion associated with disease risk and which is also differential from PsC
      risk.

PMID- 25990291
TI  - Response to: 'belimumab and the measurement of fatigue' by Mazzoni.

PMID- 25990290
TI  - Evidence for treating rheumatoid arthritis to target: results of a systematic
      literature search update.
AB  - OBJECTIVE: A systematic literature review (SLR; 2009-2014) to compare a target
      oriented approach with routine management in the treatment of rheumatoid
      arthritis (RA) to allow an update of the treat-to-target recommendations.
      METHODS: Two SLRs focused on clinical trials employing a treatment approach
      targeting a specific clinical outcome were performed. In addition to testing
      clinical, functional and/or structural changes as endpoints, comorbidities,
      cardiovascular risk, work productivity and education as well as patient self
      assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane
      databases and Clinicaltrial.gov for the period between 2009 and 2012 and
      separately for the period of 2012 to May of 2014. RESULTS: Of 8442 citations
      retrieved in the two SLRs, 176 articles underwent full-text review. According to
      predefined inclusion/exclusion criteria, six articles were included of which five
      showed superiority of a targeted treatment approach aiming at least at low
      disease activity versus routine care; in addition, publications providing
      supportive evidence were also incorporated that aside from expanding the evidence
      provided by the above six publications allowed concluding that a target-oriented
      approach leads to less comorbidities and cardiovascular risk and better work
      productivity than conventional care. CONCLUSIONS: The current study expands the
      evidence that targeting low-disease activity or remission in the management of RA
      conveys better outcomes than routine care.

PMID- 25990292
TI  - Metastatic Colorectal Cancer and the Need for More Endoscopic Tools.

PMID- 25990293
TI  - Patient Self-Management of Diabetes Care in the Inpatient Setting: Con.
AB  - Self-management of diabetes by inpatients can be problematic. People with type 1
      diabetes often prefer to self-manage their diabetes in the inpatient setting. We
      report the case of a patient admitted to the surgical service who was self
      administering his home insulin, often without telling his nurse or physician. He
      was aiming for tight glycemic control, which resulted in life-threatening
      hypoglycemia. While patients can often self-manage their diabetes in the
      outpatient setting, inpatient management of diabetes is very different. Patients
      may not be familiar with common scenarios requiring adjustments of insulin
      therapy. Therefore, we recommend against self-management of diabetes in the
      hospital. However, the patients should be involved in discussions about
      management of their diabetes in the hospital to allay their concerns about
      changes made to their insulin regimens. An example of successful cooperative
      management is with use of protocols that allow continued use of insulin pumps in
      the hospital. 

PMID- 25990294
TI  - Performance of Cleared Blood Glucose Monitors.
AB  - Cleared blood glucose monitor (BGM) systems do not always perform as accurately
      for users as they did to become cleared. We performed a literature review of
      recent publications between 2010 and 2014 that present data about the frequency
      of inaccurate performance using ISO 15197 2003 and ISO 15197 2013 as target
      standards. We performed an additional literature review of publications that
      present data about the clinical and economic risks of inaccurate BGMs for making
      treatment decisions or calibrating continuous glucose monitors (CGMs). We found
      11 publications describing performance of 98 unique BGM systems. 53 of these 98
      (54%) systems met ISO 15197 2003 and 31 of the 98 (32%) tested systems met ISO
      15197 2013 analytical accuracy standards in all studies in which they were
      evaluated. Of the tested systems, 33 were identified by us as FDA-cleared. Among
      these FDA-cleared BGM systems, 24 out of 32 (75%) met ISO 15197 2003 and 15 out
      of 31 (48.3%) met ISO 15197 2013 in all studies in which they were evaluated.
      Among the non-FDA-cleared BGM systems, 29 of 65 (45%) met ISO 15197 2003 and 15
      out of 65 (23%) met ISO 15197 2013 in all studies in which they were evaluated.
      It is more likely that an FDA-cleared BGM system, compared to a non-FDA-cleared
      BGM system, will perform according to ISO 15197 2003 (chi(2) = 6.2, df = 3, P =
      0.04) and ISO 15197 2013 (chi(2) = 11.4, df = 3, P = 0.003). We identified 7
      articles about clinical risks and 3 articles about economic risks of inaccurate
      BGMs. We conclude that a significant proportion of cleared BGMs do not perform at
      the level for which they were cleared or according to international standards of
      accuracy. Such poor performance leads to adverse clinical and economic
      consequences. 

PMID- 25990295
TI  - A review of the recent advances in neuroimaging of frontotemporal lobar
      degeneration.
AB  - INTRODUCTION: The term "frontotemporal lobar degeneration" (FTLD) includes a
      large set of neurodegenerative diseases, which are heterogeneous in their
      genetic, pathologic and clinical aspects. This review will focus on the most
      recent contribution of neuroimaging tools on the diagnosis, characterization and
      pathogenesis of FTLD. EVIDENCE ACQUISITION: Scopus, Ovid, PubMed and MEDLINE were
      searched for articles published from January 2012 up to December 2014. Searches
      were limited to articles published in English. Frontotemporal lobar degeneration
      as a key word was always in the search queries in combination with logic AND, and
      at least one other key word. EVIDENCE SYNTHESIS: We found 91 papers of interest
      and reviewed their contents, finding in particular 4 major topics: the
      contribution of neuroimaging on the differential diagnosis; patients' functional
      characterization; new neuroimaging tools under development and pre-symptomatic
      genetic forms. CONCLUSIONS: Neuroimaging techniques have shown to be useful
      supporting tools in diagnosis, even if not always determinant to reach a
      conclusive decision, and quite important to identify phenocopies. At the moment,
      there is not a neuroimaging biomarker that could track the progressive course of
      dementias and the effect of therapies, but it is possible that in the future
      Diffusion Tensor Imaging and molecular imaging could fill this void. Monitoring
      the evolution of the pathology in vivo for at least 5 years is essential, and
      this would only be possible in a large multicenter study; asymptomatic forms
      would require even longer observation periods.

PMID- 25990296
TI  - The effect of diabetes mellitus on 30-day outcomes following single-level open
      lumbar microdiscectomy: an aged-matched case-control study.
AB  - BACKGROUND: Diabetes mellitus (DM) is a known risk factor for post-surgical
      complications. However, few reports specifically study lumbar spine surgical
      outcomes in diabetics. The purpose of this study was to assess 30-day outcomes in
      patients with DM undergoing single-level open lumbar microdiscectomy (oLMD).
      METHODS: A retrospective case control study on patients with DM undergoing
      between 2001 and 2012. Patients who underwent a minimally invasive approach,
      repeat discectomy, or multilevel surgery were excluded. One hundred and twenty
      six patients were age-matched with 126 non-diabetic controls. Outcomes assessed
      included length of stay (LOS), postoperative urinary retention (UR), total
      morbidity, infection, postoperative radiculitis, 30-day re-admissions and
      emergency department visits, and pain status at discharge and at 30 days.
      Categorical variables were evaluated with Pearson's chi2 tests. Student's t-tests
      were used to evaluate continuous variables. Univariate logistic regression was
      used to evaluate strength of association of DM with outcome variables. RESULTS:
      Mean LOS was significantly higher in diabetic patients (1.9 vs. 1.4 days,
      P<0.0001). DM was associated with increased morbidity (P=0.009, OR=3.3, CI: 1.3
      9.5) and UR (P<0.0001, OR=8.2, CI: 3.4-24.8). No differences were found in 30-day
      readmission rates or emergency department visits, pain status at discharge and at
      30 days, or postoperative radiculitis. CONCLUSIONS: Overall, short-term outcomes
      are worse in patients with DM. Following single-level oLMD, DM is associated with
      longer hospital stays, UR, and increased morbidity. These short term outcomes
      consequently lead to an overall increase in hospital costs.

PMID- 25990297
TI  - Shifts in the phylogenetic structure of arbuscular mycorrhizal fungi in response
      to experimental nitrogen and carbon dioxide additions.
AB  - Global N inputs and atmospheric CO2 concentrations have increased as a result of
      human activities, and are predicted to increase along with population growth,
      with potentially negative effects on biodiversity. Using taxonomic and
      phylogenetic measures, we examined the response of arbuscular mycorrhizal fungi
      (AMF) to experimental manipulations of N and CO2 at the Jasper Ridge Global
      Change Experiment. No significant interactions between N and CO2 were observed,
      but individual effects of N and CO2 were found. Elevated CO2 resulted in changes
      in phylogenetic similarity, and a shift to phylogenetic clustering of AMF
      communities. N addition resulted in higher phylogenetic diversity and evenness,
      with no shifts in community composition and no significant signal for
      phylogenetic clustering. N addition resulted in an increase in both available N
      and the N:P ratio in N-amended plots, which suggests that changing patterns of
      nutrient limitation could have lead to altered species interactions. These
      findings suggest that elevated levels of N and CO2 altered patterns of AMF
      community assembly, with potential effects on ecosystem function. 

PMID- 25990298
TI  - Changing gears during succession: shifting functional strategies in young
      tropical secondary forests.
AB  - Adaptations to resource availability strongly shape patterns of community
      composition along successional gradients in environmental conditions. In the
      present study, we examined the extent to which variation in functional
      composition explains shifts in trait-based functional strategies in young
      tropical secondary forests during the most dynamic stage of succession (0-20
      years). Functional composition of two size classes in 51 secondary forest plots
      was determined using community-weighted means of seven functional traits, which
      were intensively measured on 55 woody plant species (n = 875-1,761 individuals).
      Along the successional gradient in forest structure, there was a significant and
      consistent shift in functional strategies from resource acquisition to resource
      conservation. Leaf toughness and adult plant size increased significantly, while
      net photosynthetic capacity (A(mass)) decreased significantly during succession.
      Shifts in functional strategies within size classes for A(mass) and wood density
      also support the hypothesis that changes in functional composition are shaped by
      environmental conditions along successional gradients. In general, 'hard'
      functional traits, e.g., A(mass) and leaf toughness, linked to different facets
      of plant performance exhibited greater sensitivity to successional changes in
      forest structure than 'soft' traits, such as leaf mass area and leaf dry matter
      content. Our results also suggested that stochastic processes related to previous
      land-use history, dispersal limitation, and abiotic factors explained variation
      in functional composition beyond that attributed to deterministic shifts in
      functional strategies. Further data on seed dispersal vectors and distance and
      landscape configuration are needed to improve current mechanistic models of
      succession in tropical secondary forests.

PMID- 25990299
TI  - Artery-on-a-chip platform for automated, multimodal assessment of cerebral blood
      vessel structure and function.
AB  - We present a compact microfluidic platform for the automated, multimodal
      assessment of intact small blood vessels. Mouse olfactory artery segments were
      reversibly loaded onto a microfluidic device and kept under physiological (i.e.,
      close to in vivo) environmental conditions. For immunohistochemical endpoint
      protein analysis, automated on chip fixation and staining of the artery
      eliminated the need for any subsequent tissue sectioning or processing outside
      the chip. In a first case study, we demonstrate the blood vessel abluminal
      structure based on the positions of smooth muscle cell nuclei, actin filaments
      and voltage gated calcium channels. In a second case study we incubated smooth
      muscle cells (SMCs) with a calcium-sensitive dye to simultaneously assess time
      dependent, agonist-induced calcium and diameter changes of pressurized resistance
      arteries. We expect the presented microfluidic platform to promote routine on
      chip staining and quantitative fluorescence imaging of intact blood vessels from
      different vascular beds, tissue engineered vascular constructs and vascularized
      microtissues. The at least tenfold reduction in required aliquot volumes for
      functional assessment and staining was achieved by on-board fluid manipulation of
      the syringe-pump free platform and may promote its applications for screening of
      newly synthesized compounds. 

PMID- 25990300
TI  - Consortium of the 'bichlorophyllous' cyanobacterium Prochlorothrix hollandica and
      chemoheterotrophic partner bacteria: culture and metagenome-based description.
AB  - 'Bacterial consortium' sensu lato applies to mutualism or syntrophy-based systems
      consisting of unrelated bacteria. Consortia of cyanobacteria have been
      preferentially studied on Anabaena epibioses; non-photosynthetic satellites of
      other filamentous or unicellular cyanobacteria were also considered although
      structure-functional data are few. At the same time, information about consortia
      of cyanobacteria which have light-harvesting antennae distinct from standard
      phycobilisome was missing. In this study, we characterized first, via a
      polyphasic approach, the cultivable consortium of Prochlorothrix hollandica CCAP
      1490/1 (filamentous cyanobacterium which contains chlorophylls a,
      b/carotenoid/protein complex in the absence of phycobilisome) and non
      photosynthetic heterotrophic bacteria. The strains of most abundant satellites
      were isolated and identified. Consortium metagenome reconstructed via 454-pyro
      and Illumina sequencing was shown to include, except for P. hollandica, several
      phylotypes of Proteobacteria and Bacteroidetes. The ratio of consortium members
      was essentially stable irrespective of culture age, and restored after
      artificially imposed imbalance. The consortium had a complex spatial arrangement
      as demonstrated by FISH and SEM images of the association, epibiosis, and biofilm
      type. Preliminary data of metagenome annotation agreed with the hypothesis that
      satellite bacteria contribute to P. hollandica protection from reactive oxygen
      species (ROS). 

PMID- 25990301
TI  - Reflecting on 'Acquisition and disclosure of genetic information under
      alternative policy regimes: an economic analysis'.

PMID- 25990302
TI  - Understanding the role of the dye/oxide interface via SnO2-based MK-2 dye
      sensitized solar cells.
AB  - To understand the role of the dye/oxide interface, a model system using a
      nanocrystalline SnO2 and 3-hexyl thiophene based MK-2 dye is proposed. A thin
      interfacial TiO2 blocking layer (IBL) is introduced in between SnO2 and MK-2 and
      its effects on photocurrent-voltage, electron transport-recombination, and
      density of states (DOS) are systematically investigated. Compared to the bare
      SnO2 film, the insertion of IBL leads to a 14-fold improvement in the power
      conversion efficiency (PCE) despite little change in the dye adsorption amount,
      which is due to the 7-fold and 2-fold increase in the photocurrent density and
      voltage, respectively. The charge collection efficiency is substantially improved
      from 38% to 96% mainly due to the increase in the electron lifetime. The IBL is
      also found to enhance the dye regeneration efficiency as confirmed by the 15-fold
      faster dye bleaching recovery dynamics. The recombination resistance increases
      and the DOS decreases after surface modification of SnO2, which is responsible
      for the doubly increased voltage. This study suggests that the interfacial layer
      between the oxide and the dye plays a crucial role in retarding recombination,
      improving charge collection efficiency, increasing diffusion length, accelerating
      dye regeneration and narrowing the density of states. 

PMID- 25990303
TI  - A cross-sectional observational study of healthcare professional views of factors
      affecting teenage adherence with antipsychotic medication.
AB  - Delays in effective treatment of a first episode psychosis can result in more
      severe symptoms, a longer time to achieve symptom control and a poorer quality of
      life; yet around 40% do not take antipsychotic medication as prescribed. There is
      evidence that patients and staff have different perceptions of what affects
      adherence with medication. Research in adults suggests healthcare professionals
      and patients understand the importance of good insight in promoting adherence
      with medication for schizophrenia; however, healthcare staff may overestimate the
      impact of side effects and underestimate the importance of medication
      effectiveness. There is also some evidence to suggest that motivations to take
      prescribed medication may differ in first and multi-episode psychosis. This
      research therefore sought views of staff working with adolescents diagnosed with
      first episode psychosis about what factors affected adherence with antipsychotic
      medication. Staff responding to the survey felt that young people were more
      likely to take medication if they felt it would make them better, prevent relapse
      and if they had a positive rapport with staff. As in an adult population, side
      effects, particularly weight gain, sedation and muscular side effects, were
      expressed as a common reason for poor adherence. Doctors and nurses assigned
      differing importance to parameters such as family views of medication, fear of
      admission and a preference for cannabis over medication suggesting that views may
      differ between professional groups Views of young people will be obtained in the
      next phase of the research study to enable comparison with staff views and
      consideration of staff interventions to better promote medication adherence.
      Antipsychotic medication is an effective treatment for first episode psychosis;
      yet 40% of patients do not take medication as prescribed. Previous research in
      adults with schizophrenia comparing healthcare professional and patient views
      suggests that while healthcare professionals recognize the importance of insight
      in promoting medication adherence, they underestimate the importance of
      medication efficacy and overestimate the impact of side effects. It was
      hypothesized that staff in this study would also recognize the importance of
      insight and positive medication attitudes in teenagers with psychosis, but
      overestimate the impact of side effects on medication adherence. This cross
      sectional observational study sought staff views about factors affecting
      antipsychotic medication adherence in those aged between 14 and 18 years. An
      online survey was distributed and 60 responses were subsequently returned. Staff
      felt that good medication insight as well as positive relationships with staff
      were important determinants of good medication adherence. The most important
      influences of poor adherence were poor insight, side effects of medication and a
      wish to exert personal control around medication decisions. The results therefore
      confirmed the initial hypothesis. Published literature also provides support for
      some, but not all, of the staff views expressed in survey responses.

PMID- 25990304
TI  - Layer dependence and gas molecule absorption property in MoS2 Schottky diode with
      asymmetric metal contacts.
AB  - Surface potential measurement on atomically thin MoS2 flakes revealed the
      thickness dependence in Schottky barriers formed between high work function metal
      electrodes and MoS2 thin flakes. Schottky diode devices using mono- and multi
      layer MoS2 channels were demonstrated by employing Ti and Pt contacts to form
      ohmic and Schottky junctions respectively. Characterization results indicated n
      type behavior of the MoS2 thin flakes and the devices showed clear rectifying
      performance. We also observed the layer dependence in device characteristics and
      asymmetrically enhanced responses to NH3 and NO2 gases based on the metal work
      function and the Schottky barrier height change.

PMID- 25990305
TI  - Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury
      after ST-elevation myocardial infarction (the MINIMISE STEMI Trial): rationale
      and study design.
AB  - Novel therapies capable of reducing myocardial infarct (MI) size when
      administered prior to reperfusion are required to prevent the onset of heart
      failure in ST-segment elevation myocardial infarction (STEMI) patients treated by
      primary percutaneous coronary intervention (PPCI). Experimental animal studies
      have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy
      administered prior to reperfusion can reduce MI size, and MRA therapy prevents
      adverse left ventricular (LV) remodeling in post-MI patients with LV impairment.
      With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior
      to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and
      prevent adverse LV remodeling in STEMI patients. The MINIMISE-STEMI trial is a
      prospective, randomized, double-blind, placebo-controlled trial that will recruit
      150 STEMI patients from four centers in the United Kingdom. Patients will be
      randomized to receive either an intravenous bolus of MRA therapy (potassium
      canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral
      spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac
      magnetic resonance imaging scan will be performed within 1 week of PPCI and
      repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will
      be estimated by the 48-hour area-under-the-curve serum cardiac enzymes. The
      primary endpoint of the study will be MI size on the 3-month cardiac magnetic
      resonance imaging scan. The MINIMISE STEMI trial will investigate whether early
      MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent
      adverse post-MI LV remodeling.

PMID- 25990306
TI  - Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants
      of probable Alzheimer's disease.
AB  - Different clinical variants of probable Alzheimer's disease (AD) share underlying
      plaques and tangles but show distinct atrophy patterns. We included 52 posterior
      cortical atrophy, 29 logopenic variant primary progressive aphasia, 53 early
      onset and 42 late-onset AD patients, selected for abnormal cerebrospinal fluid
      (CSF)-amyloid-beta42, with CSF and magnetic resonance imaging data available.
      Bootstrapping revealed no differences in the prevalence of abnormal CSF total-tau
      and phosphorylated-tau between probable AD variants (range total-tau: 84.9%
      92.3%, phosphorylated-tau: 79.2%-93.1%, p > 0.05). Voxelwise linear regressions
      showed various relationships between lower CSF-Abeta42 and syndrome-specific
      atrophy, involving precuneus, posterior cingulate, and medial temporal lobe in
      early-onset AD, occipital cortex and middle temporal gyrus in posterior cortical
      atrophy; anterior cingulate, insular cortex and precentral gyrus (left > right)
      in logopenic variant primary progressive aphasia; and medial temporal lobe,
      thalamus, and temporal pole in late-onset AD (all at p < 0.001 uncorrected). In
      contrast, CSF-tau was not related to gray matter atrophy in any group. Our
      findings suggest that lower CSF-amyloid-beta42 - and not increased total-tau and
      phosphorylated-tau - relates to reduced gray matter volumes, mostly in regions
      that are typically atrophied in distinct clinical variants of probable AD. 

PMID- 25990307
TI  - Psychometric Properties of the German Version of the Child Post-Traumatic
      Cognitions Inventory (CPTCI-GER).
AB  - Dysfunctional trauma-related cognitions are associated with posttraumatic stress
      disorder (PTSD). The psychometric properties of the German version of the Child
      Post-Traumatic Cognitions Inventory (CPTCI-GER) were assessed in a sample of 223
      children and adolescents (7-16 years) with a history of different traumatic
      events. Confirmatory factor analyses supported the original two-factor structure-
      permanent and disturbing change (CPTCI-PC) and fragile person in a scary world
      (CPTCI-SW). The total scale and both subscales showed good internal consistency.
      Participants with PTSD had significantly more dysfunctional trauma-related
      cognitions than those without PTSD. Dysfunctional posttraumatic cognitions
      correlated significantly with posttraumatic stress symptoms (PTSS; r = .62),
      depression (r = .71), and anxiety (r = .67). The CPTCI-GER has good psychometric
      properties and may facilitate evaluation of treatments and further research on
      the function of trauma-related cognitions in children and adolescents. (Partial)
      correlations provide empirical support for the combined DSM-5 symptom cluster
      negative alterations in cognitions and mood.

PMID- 25990309
TI  - Whatever happened to the principle of innocent until proved guilty?

PMID- 25990310
TI  - Identification of a novel MICB allele, MICB*030, by cloning and sequencing.
AB  - A novel MICB allele, MICB*030, has been identified in a healthy Chinese
      individual of Mongol ethnicity residing in northern China by polymerase chain
      reaction sequence-based typing (PCR-SBT) and confirmed by cloning and sequencing.
      MICB*030 was linked to HLA-B*35. Aligned with MICB*005:02, MICB*030 has a
      nonsynonymous adenine substitution at nucleotide position 50 in exon 3, leading
      to amino acid change from serine to arginine at codon 102 of the mature MICB
      molecule. 

PMID- 25990308
TI  - The oncogenic microRNA miR-21 promotes regulated necrosis in mice.
AB  - MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis
      remains unknown. miR-21 is overexpressed in nearly all human cancer types and its
      role as an oncogene is suggested to largely depend on its anti-apoptotic action.
      Here we show that miR-21 is overexpressed in a murine model of acute
      pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis
      (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis
      injury and necroptosis. miR-21 deficiency protects against caerulein- or L
      arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked
      nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity.
      miR-21 deletion is also protective in tumour necrosis factor-induced systemic
      inflammatory response syndrome. These data suggest that miRNAs are critical
      participants in necroptosis and miR-21 enhances cellular necrosis by negatively
      regulating tumour suppressor genes associated with the death-receptor-mediated
      intrinsic apoptosis pathway, and could be a therapeutic target for preventing
      pathologic necrosis. 

PMID- 25990312
TI  - Food preferences and underlying mechanisms after bariatric surgery.
AB  - Bariatric surgery leads to significant long-term weight loss, particularly Roux
      en-Y gastric bypass (RYGB). The mechanisms underlying weight loss have not been
      fully uncovered. The aim of this review is to explore the changes in food
      preferences, as a novel mechanism contributing to weight loss, and also focus on
      the underlying processes modulating eating behaviour after bariatric surgery.
      Patients after gastric bypass are less hungry and prefer healthier food options.
      They develop an increased acuity to sweet taste, which is perceived as more
      intense. The appeal of sweet fatty food decreases, with functional MRI studies
      showing a corresponding reduction in activation of the brain reward centres to
      high-energy food cues. Patients experiencing post-ingestive symptoms with sweet
      and fatty food develop conditioned aversive behaviours towards the triggers. Gut
      hormones are elevated in RYGB and have the potential to influence the taste
      system and food hedonics. Current evidence supports a beneficial switch in food
      preferences after RYGB. Changes within the sensory and reward domain of taste and
      the development of post-ingestive symptoms appear to be implicated. Gut hormones
      may be the mediators of these alterations and therefore exploiting this property
      might prove beneficial for designing future obesity treatment. 

PMID- 25990311
TI  - Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA
      and CaMKII.
AB  - AIMS: Enhanced cardiac late Na current (late INa) and increased sarcoplasmic
      reticulum (SR)-Ca(2+)-leak are both highly arrhythmogenic. This study seeks to
      identify signalling pathways interconnecting late INa and SR-Ca(2+)-leak in
      atrial cardiomyocytes (CMs). METHODS AND RESULTS: In murine atrial CMs, SR-Ca(2+)
      leak was increased by the late INa enhancer Anemonia sulcata toxin II (ATX-II).
      An inhibition of Ca(2+)/calmodulin-dependent protein kinase II (Autocamide-2
      related inhibitory peptide), protein kinase A (H89), or late INa (Ranolazine or
      Tetrodotoxin) all prevented ATX-II-dependent SR-Ca(2+)-leak. The SR-Ca(2+)-leak
      induction by ATX-II was not detected when either the Na(+)/Ca(2+) exchanger was
      inhibited (KBR) or in CaMKIIdeltac-knockout mice. FRET measurements revealed
      increased cAMP levels upon ATX-II stimulation, which could be prevented by
      inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of
      phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase
      of cAMP levels. Western blots showed late INa-dependent hyperphosphorylation of
      CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and 
      S2808) and phospholamban (-Thr17, -S16). Enhancement of late INa did not alter
      Ca(2+)-transient amplitude or SR-Ca(2+)-load. However, upon late INa activation
      and simultaneous CaMKII inhibition, Ca(2+)-transient amplitude and SR-Ca(2+)-load
      were increased, whereas PKA inhibition reduced Ca(2+)-transient amplitude and
      load and additionally slowed Ca(2+) elimination. In atrial CMs from patients with
      atrial fibrillation, inhibition of late INa, CaMKII, or PKA reduced the SR-Ca(2+)
      leak. CONCLUSION: Late INa exerts distinct effects on Ca(2+) homeostasis in
      atrial myocardium through activation of CaMKII and PKA. Inhibition of late INa
      represents a potential approach to attenuate CaMKII activation and decreases SR
      Ca(2+)-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA
      system further increases the antiarrhythmic potential of late INa inhibition.

PMID- 25990313
TI  - Anti-CCL2: building a reservoir or opening the floodgates to metastasis?
AB  - Neutralisation of macrophage chemoattractant C-C chemokine ligand 2 (CCL2) has
      shown reduced metastasis and enhanced survival in numerous experimental models of
      tumorigenesis. However, important new findings reported in Nature by Momo
      Bentires-Alj's laboratory demonstrate that withdrawal of anti-CCL2 treatment
      accelerates lung metastasis and death in mice. The study highlights the need to
      consider longer term consequences of therapeutic intervention of metastatic
      disease, especially with regard to transient interference with the tumour
      microenvironment. 

PMID- 25990314
TI  - Risk factors of PSA progression and overall survival in patients with localized
      and locally advanced prostate cancer treated with primary androgen deprivation
      therapy.
AB  - BACKGROUND: Primary androgen deprivation therapy (PADT) has played an important
      role in the treatment of prostate cancer. We sought to identify factors of PSA
      progression in our series of patients with localized and locally advanced
      prostate cancer treated with PADT. METHODS: Six-hundred forty-nine patients with
      localized and locally advanced prostate cancer who received PADT from 1998 to
      2005 by Nara Uro-Oncology Research Group were enrolled. Age, T classification,
      stage, PSA level at diagnosis, Gleason score, laterality of cancer detected by
      biopsy and seminal vesicle involvement (SVI) were adopted as parameters of PSA
      progression. Cox's proportional hazards model was used to determine the
      predictive factors for PSA progression. RESULTS: The median follow-up period and
      the median PSA level at diagnosis were 49 months and 15 ng/mL. The 5-year disease
      specific survival rate, overall survival rate and PSA progression-free survival
      (PFS) rate were 97.9 %, 91.9 % and 71.2 %, respectively. The univariate analysis
      showed that the PSA level at diagnosis, Gleason score, laterality of cancer
      detected by biopsy and SVI were independent predictive parameters of PSA-PFS.
      However, by multivariate analysis, only laterality of cancer detected by biopsy
      (unilateral vs. bilateral) was an independent predictive parameter of PSA-PFS (p
      = 0.034). The patients were classified into new risk groups base on three
      factors: PSA level at diagnosis, Gleason score, and laterality of cancer detected
      by biopsy. The PSA-PFS rates at 5-years in the low- (none or one factor),
      intermediate- (two factors) and high-risk (three factors) groups were 78.2 %,
      62.5 % and 46.9 % (p < 0.001), respectively. CONCLUSION: In localized or locally
      advanced prostate cancer patients who received PADT, laterality of cancer
      detected by biopsy was a significant predictor associated with a longer PSA-PFS.
      Our new risk grouping indicates the usefulness of PSA-PFS.

PMID- 25990316
TI  - The vulnerable vessel. Vascular disease in diabetes mellitus.
AB  - Diabetes represents one of the most important risk factors for atherosclerosis,
      which is the leading cause of mortality worldwide. Recent imaging studies
      employing intravascular ultrasound or computed coronary angiography tomography
      clearly confirm that diabetes is associated with larger plaque burden and with
      more lesions displaying features of instability. Various molecular mechanisms
      promoting atherogenesis and plaque destabilization in diabetics have been
      described in the past. The current review specifically focuses on recent papers
      that have addressed the effects of diabetes and hyperglycemia (i) on myeloid
      cells, (ii) on oxidative stress, and (iii) on protein kinase C (PKC) activation.
      Thus, it has been demonstrated that hyperglycemia may promote myelopoiesis and
      differentiation of pro-inflammatory macrophages. Furthermore, novel studies
      emphasize the interplay between inflammation and oxidative stress at both the
      molecular and the genetic level. Finally, experimental studies shed light on the
      role of PKC-beta in diabetes-associated atherosclerosis. Several of these recent
      studies suggest that atherogenesis and plaque destabilization in diabetic
      individuals may be mediated by diabetes-specific mechanisms. This may open the
      door for developing tailored anti-atherosclerotic therapies for diabetic
      patients.

PMID- 25990315
TI  - Self-Assembled Fluorescent Nanoparticles from pi-Conjugated Small Molecules: En
      Route to Biological Applications.
AB  - Since the development of supramolecular chemical biology, self-organised nano
      architectures have been widely explored in a variety of biomedical applications.
      Functionalized synthetic molecules with the ability of non-covalent assembly in
      an aqueous environment are typically able to interact with biological systems and
      are therefore especially interesting for their use in theranostics.
      Nanostructures based on pi-conjugated oligomers are particularly promising as
      theranostic platforms as they bear outstanding photophysical properties as well
      as drug loading capabilities. This Feature Article provides an overview on the
      recent advances in the self-assembly of intrinsically fluorescent nanoparticles
      from pi-conjugated small molecules such as fluorene or perylene based
      chromophores for biomedical applications. 

PMID- 25990317
TI  - Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary
      adenoid cystic carcinoma cells.
AB  - BACKGROUND: Notch-1 promotes invasion and metastasis of cancer cells but its role
      in salivary adenoid cystic carcinoma (SACC) remains unelucidated. Here, we sought
      to investigate the effect of Notch-1 knockdown on the invasion and metastasis of
      SACC cells. METHODS: Stable ACC-M cells whose Notch-1 was silenced by lentiviral
      vectors were established. Cellular proliferation was evaluated by the MTT assays
      and clonogenic assays, apoptosis by flow cytometry and the migration of ACC-M
      cells by Transwell assays. Metastasis was evaluated by examining the number of
      lung nodules in Balb/c nu/nu nude mice bearing subcutaneous SACC xenografts.
      RESULTS: Our MTT assay revealed that Notch-1 knockdown significantly suppressed
      the proliferation of ACC-M cells compared with non-infected or scrambled control
      cells. Clonogenic assays further showed that Notch-1 knockdown significantly
      suppressed the clonogenic growth of ACC-M cells (p < 0.01 vs. controls). Our flow
      cytometry demonstrated that Notch-1 knockdown was associated with a significantly
      higher proportion of late apoptotic and necrotic cells (p < 0.01 vs. controls).
      Transwell assays revealed that Notch-1 knockdown markedly reduced the migratory
      capacity of ACC-M cells (p < 0.01 vs. controls) and xenograft studies showed that
      the number of metastatic nodules in the lung surface was significantly lower in
      nude mice bearing xenografts with Notch-1 knockdown compared to those bearing
      control xenografts (p < 0.01 vs. controls). CONCLUSION: Notch-1 knockdown
      suppresses the growth and migration of SACC cells in vitro and the metastasis of
      SACC cells in vivo. Notch-1 may be a new candidate target in SACC.

PMID- 25990319
TI  - Additive prognostic value of plasma N-terminal pro-brain natriuretic peptide and
      coronary artery calcification for cardiovascular events and mortality in
      asymptomatic patients with type 2 diabetes.
AB  - BACKGROUND: In patients with type 2 diabetes, cardiovascular disease (CVD) is the
      major cause of morbidity and mortality. We evaluated the combination of NT-proBNP
      and coronary artery calcium score (CAC) for prediction of combined fatal and non
      fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria
      (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed
      the predictive value of a predefined categorisation of patients into a high- and
      low-risk group at baseline. METHODS: Prospective study including 200 patients.
      All received intensive multifactorial treatment. Patients with baseline NT-proBNP
      > 45.2 ng/L and/or CAC >= 400 were stratified as high-risk patients (n = 133).
      Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced
      after 6.1 years (median). RESULTS: High-risk patients had a higher risk of the
      composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval
      [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p =
      0.032) compared to low-risk patients. In adjusted continuous analysis, both
      higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and
      mortality (p <= 0.0001). In fully adjusted models mutually including NT-proBNP
      and CAC, both risk factors remained associated with risk of CVD and mortality (p
      <= 0.022). There was no interaction between NT-proBNP and CAC for the examined
      endpoints (p >= 0.31). CONCLUSIONS: In patients with type 2 diabetes and
      microalbuminuria but without known coronary artery disease, NT-proBNP and CAC
      were strongly associated with fatal and nonfatal CVD, as well as with mortality.
      Their additive prognostic capability holds promise for identification of patients
      at high risk.

PMID- 25990320
TI  - Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal
      signaling.
AB  - The ectoderm has the capability to generate epidermis and neuroectoderm and plays
      imperative roles during the early embryonic development. Our recent study
      uncovered a region with ectodermal progenitor potential in mouse embryo at
      embryonic day 7.0 and revealed that Nodal inhibition is essential for its
      formation. Here, we demonstrate that through brief inhibition of Nodal signaling
      in vitro, mouse embryonic stem cell (ESC)-derived epiblast stem cells (ESD
      EpiSCs) could be committed to transient ectodermal progenitor populations, which
      possess the ability to give rise to neural or epidermal ectoderm in the absence
      or presence of BMP4, respectively. Mechanistic studies reveal that BMP4 recruits
      distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells.
      Furthermore, FGF-Erk signaling may also be alleviated during the generation of
      ectoderm-like cells. Thus, our data suggest that instructive interactions among
      several extracellular signals participate in the commitment of ectoderm from ESD
      EpiSCs, which shed new light on the understanding of the formation of ectoderm
      during the gastrulation in early mouse embryo development. 

PMID- 25990321
TI  - A Comparison of Persian Vowel Production in Hearing-Impaired Children Using a
      Cochlear Implant and Normal-Hearing Children.
AB  - OBJECTIVE: Normal-hearing (NH) acuity and auditory feedback control are crucial
      for human voice production and articulation. The lack of auditory feedback in
      individuals with profound hearing impairment changes their vowel production. The
      purpose of this study was to compare Persian vowel production in deaf children
      with cochlear implants (CIs) and that in NH children. METHODS: The participants
      were 20 children (12 girls and 8 boys) with age range of 5 years; 1 month to 9
      years. All patients had congenital hearing loss and received a multichannel CI at
      an average age of 3 years. They had at least 6 months experience of their current
      device (CI). The control group consisted of 20 NH children (12 girls and 8 boys)
      with age range of 5 to 9 years old. The two groups were matched by age.
      Participants were native Persian speakers who were asked to produce the vowels
      /i/, /e/, /ae/, /u/, /o/, and /a/. The averages for first formant frequency (F1)
      and second formant frequency (F2) of six vowels were measured using Praat
      software (Version 5.1.44, Boersma & Weenink, 2012). The independent samples t
      test was conducted to assess the differences in F1 and F2 values and the area of
      the vowel space between the two groups. RESULTS: Mean values of F1 were increased
      in CI children; the mean values of F1 for vowel /i/ and /a/, F2 for vowel /a/ and
      /o/ were significantly different (P < 0.05). The changes in F1 and F2 showed a
      centralized vowel space for CI children. CONCLUSIONS: F1 is increased in CI
      children, probably because CI children tend to overarticulate. We hypothesis this
      is due to a lack of auditory feedback; there is an attempt by hearing-impaired
      children to compensate via proprioceptive feedback during articulatory process.

PMID- 25990322
TI  - Functional expression of recombinant human trefoil factor 1 by Escherichia coli
      and Brevibacillus choshinensis.
AB  - BACKGROUND: Trefoil factor 1 (TFF1) mediates mucosal repair and belongs to a
      highly conserved trefoil factor family proteins which are secreted by epithelial
      cells in the stomach or colon mucous membrane. TFF1 forms a homodimer via a
      disulphide linkage that affects wound healing activity. Previous recombinant
      expressions of TFF1 were too low yield for industrial application. This study
      aims to improve the expression level of bioactive recombinant TFF1 (rTFF1) and
      facilitate application potency. METHODS: The rTFF1 gene rtff1 was synthesized,
      expressed by Escherichia coli and secreted by Brevibacillus choshinensis. The
      rTFF1s were purified. The polymeric patterns and wound healing capacities of
      purified rTFF1s were checked. RESULTS: In Escherichia coli, 21.08 mg/L rTFF1 was
      stably expressed as monomer, dimer and oligomer in soluble fraction. In
      Brevebacillus choshinensis, the rTFF1 was secreted extracellularly at high level
      (35.73 mg/L) and formed monomer, dimer and oligomer forms. Both proteins from
      different sources were purified by Ni-NTA chromatography and exhibited the wound
      healing activities. The rTFF1 produced by B. choshinensis had better wound
      healing capability than the rTFF1 produced by E. coli. After pH 2.4 buffer
      treatments, the purified rTFF1 formed more oligomeric forms as well as better
      wound healing capability. Glycosylation assay and LC-MS/MS spectrometry
      experiments showed that the rTFF1 produced by B. choshinensis was unexpectedly
      glycosylated at N-terminal Ser residue. The glycosylation may contribute to the
      better wound healing capacity. CONCLUSIONS: This study provides a potent tool of
      rTFF1 production to be applied in gastric damage protection and wound healing.
      The protein sources from B. choshinensis were more efficient than rTFF1 produced
      by E. coli.

PMID- 25990324
TI  - District wellness policies and school-level practices in Minnesota, USA.
AB  - OBJECTIVE: To compare the strength of district wellness policies with
      corresponding school-level practices reported by principals and teachers. DESIGN:
      District-level wellness policy data were collected from school district websites
      and, if not available online, by requests made to district administrators in the
      autumn of 2013. The strength of district policies was scored using the Wellness
      School Assessment Tool. School-level data were drawn from the 2012 Minnesota
      School Health Profiles principal and teacher surveys and the National Center for
      Education Statistics Common Core Data. Generalized estimating equations which
      accounted for school-level demographics and the nesting of up to two schools
      within some districts were used to examine ten district policy items and fourteen
      school-level practices of relevance to nutrition standards, nutrition education
      and wellness promotion, and physical activity promotion. SETTING: State-wide
      sample of 180 districts and 212 public schools in Minnesota, USA. RESULTS: The
      mean number of energy-dense, nutrient-poor snack foods and beverages available
      for students to purchase at school was inversely related to the strength of
      district wellness policies regulating vending machines and school stores
      (P=0.01). The proportion of schools having a joint use agreement for shared use
      of physical activity facilities was inversely related to the strength of district
      policies addressing community use of school facilities (P=0.03). No associations
      were found between the strength of other district policies and school-level
      practices. CONCLUSIONS: Nutrition educators and other health professionals should
      assist schools in periodically assessing their wellness practices to ensure
      compliance with district wellness policies and environments supportive of healthy
      behaviours.

PMID- 25990326
TI  - [A man with multiple mucosal lesions and pancytopenia].
AB  - A 57-year-old man came to the Emergency Department because of painful oral ulcers
      and skin lesions. He used methotrexate because of psoriasis, but he stopped using
      folic acid. Laboratory tests showed signs of dehydration and pancytopenia. We
      made the diagnosis 'methotrexate-intoxication'. 

PMID- 25990327
TI  - [A woman with periorbital swelling].
AB  - A 43-year-old woman consulted the otolaryngologist. She had swollen eyelids and
      crepitus around the left eye. A CT-scan revealed a defect of the orbital lamina
      of the ethmoid bone ('lamina papyracea'), and an air accumulation in the left
      orbital cavity. The diagnosis 'subcutaneous emphysema of the eyelids and
      emphysema of the left orbit' was made. 

PMID- 25990325
TI  - FOXO target gene CTDSP2 regulates cell cycle progression through Ras and
      p21(Cip1/Waf1).
AB  - Activity of FOXO (forkhead box O) transcription factors is inhibited by growth
      factor-PI3K (phosphoinositide 3-kinase)-PKB (protein kinase B)/Akt signalling to
      control a variety of cellular processes including cell cycle progression. Through
      comparative analysis of a number of microarray datasets we identified a set of
      genes commonly regulated by FOXO proteins and PI3K-PKB/Akt, which includes CTDSP2
      (C-terminal domain small phosphatase 2). We validated CTDSP2 as a genuine FOXO
      target gene and show that ectopic CTDSP2 can induce cell cycle arrest. We
      analysed transcriptional regulation after CTDSP2 expression and identified
      extensive regulation of genes involved in cell cycle progression, which depends
      on the phosphatase activity of CTDSP2. The most notably regulated gene is the CDK
      (cyclin-dependent kinase) inhibitor p21(Cip1/Waf1) and in the present study we
      show that p21(Cip1/Waf1) is partially responsible for the cell cycle arrest
      through decreasing cyclin-CDK activity. Our data suggest that CTDSP2 induces
      p21(Cip1/Waf1) through increasing the activity of Ras. As has been described
      previously, Ras induces p21(Cip1/Waf1) through p53-dependent and p53-independent
      pathways and indeed both p53 and MEK inhibition can mitigate the CTDSP2-induced
      p21(Cip1/Waf1) mRNA up-regulation. In support of Ras activation by CTDSP2,
      depletion of endogenous CTDSP2 results in reduced Ras activity and thus CTDSP2
      seems to be part of a larger set of genes regulated by FOXO proteins, which
      increase growth factor signalling upon FOXO activation. 

PMID- 25990328
TI  - [Fatal tuberculosis during treatment with ruxolitinib].
AB  - CASE DESCRIPTION: Two patients, 68 and 72 years old, were admitted with fever
      whilst under treatment with ruxolitinib for myelofibrosis. They had not been
      screened for latent tuberculosis infection (LTBI) and extensive tuberculosis was
      found in both patients. They died within weeks from complications of fulminant
      disease. CONCLUSION: Doctors who prescribe ruxolitinib should be aware of the
      increased risk of infectious diseases like tuberculosis. Under immune
      suppression, tuberculosis often runs a disseminated course. The constitutional
      symptoms of myelofibrosis strongly resemble those of tuberculosis and the latter
      diagnosis should always be considered. Active and latent tuberculosis should be
      excluded and treated, if necessary, before giving ruxolitinib.

PMID- 25990318
TI  - The evolution and population structure of Lactobacillus fermentum from different
      naturally fermented products as determined by multilocus sequence typing (MLST).
AB  - BACKGROUND: Lactobacillus fermentum is economically important in the production
      and preservation of fermented foods. A repeatable and discriminative typing
      method was devised to characterize L. fermentum at the molecular level. The
      multilocus sequence typing (MLST) scheme developed was based on analysis of the
      internal sequence of 11 housekeeping gene fragments (clpX, dnaA, dnaK, groEL,
      murC, murE, pepX, pyrG, recA, rpoB, and uvrC). RESULTS: MLST analysis of 203
      isolates of L. fermentum from Mongolia and seven provinces/ autonomous regions in
      China identified 57 sequence types (ST), 27 of which were represented by only a
      single isolate, indicating high genetic diversity. Phylogenetic analyses based on
      the sequence of the 11 housekeeping gene fragments indicated that the L.
      fermentum isolates analyzed belonged to two major groups. A standardized index of
      association (I A (S)) indicated a weak clonal population structure in L.
      fermentum. Split decomposition analysis indicated that recombination played an
      important role in generating the genetic diversity observed in L. fermentum. The
      results from the minimum spanning tree strongly suggested that evolution of L.
      fermentum STs was not correlated with geography or food-type. CONCLUSIONS: The
      MLST scheme developed will be valuable for further studies on the evolution and
      population structure of L. fermentum isolates used in food products.

PMID- 25990329
TI  - [Medical education in the former Netherlands Antilles countries Bonaire, St
      Eustatius and Saba].
AB  - On 10 October 2010, the former Netherlands Antilles was dissolved politically;
      Curacao and St Maarten became autonomous countries, while Bonaire, St Eustatius
      and Saba (the 'BES islands') joined the Netherlands with the status 'special
      municipalities'. At that time there was one medical school on each of the BES
      islands, providing medical education to students predominantly from the United
      States and Canada. A process was instigated for recognition and accreditation
      within the Netherlands system of the education provided by these schools. This
      article provides an overview of this process, and investigates its consequences,
      including admission and registration requirements, student mobility and financial
      aspects. The current location and status of the different educational programmes
      will be explained. 

PMID- 25990330
TI  - [Choosing wisely when prescribing statins].
AB  - The Dutch campaign 'Verstandig kiezen', based on the American programme 'Choosing
      wisely', aims to improve quality in healthcare, with attention to cost control.
      The 'Choosing wisely'-based programme can be applied in the choice of a statin.
      Atorvastatin and rosuvastatin are regarded as equal choices in various guidelines
      regarding cardiovascular risk management. Generic atorvastatin is available, and
      is approximately 25 times cheaper than rosuvastatin in almost equipotent doses.
      Rosuvastatin provides a greater LDL reduction than atorvastatin. Patient LDL
      targets can usually be achieved with atorvastatin, and rosuvastatin is not
      needed. At group level, there are no relevant differences in adverse-events
      profile between both statins. Atorvastatin and rosuvastatin do have different
      pharmacokinetic interactions. When changing medication, good provision of
      information is a prerequisite for patient satisfaction and compliance. We advise
      use of atorvastatin instead of rosuvastatin as drug of choice when the LDL target
      is not reached using simvastatin. However, under specific conditions,
      rosuvastatin should be the treatment of choice. Efficacy and adverse effects
      should then be evaluated at individual patient level.

PMID- 25990331
TI  - [Patients on the move: validated methods to quantify physical activity].
AB  - Physical activity is an important component in the maintenance and improvement of
      general health; physical inactivity is, however, an increasing problem in the
      Netherlands. Requests for advice on physical activity are increasing within the
      healthcare. Assessment of an individual's physical activity pattern is required
      to provide tailored advice. There are a number of methods for measuring physical
      activity; these are divided into subjective and objective methods. Subjective
      measures include physical activity questionnaires and diaries. Objective measures
      include indirect calorimetry, measurement with doubly labelled water, heart-rate
      monitoring and the use of an accelerometer or pedometer. The choice of method
      depends predominantly on the aim of the measurement, and the availability of
      personnel, time and financial resources. In clinical practice a validated
      questionnaire is usually the preferred method, but when measuring effects this
      should be combined with an objective measurement instrument.

PMID- 25990332
TI  - [Post thrombotic syndrome: are elastic stockings on their last legs? The role of
      compression in prevention and treatment].
AB  - Post thrombotic syndrome (PTS) is a common chronic complication of deep venous
      thrombosis (DVT). PTS has a negative impact on quality of life. Patients with a
      more serious form of this syndrome have increased rates of sick leave and incur
      increased medical costs. The underlying processes leading to PTS are not yet
      fully understood. Pressure increases in the deep-venous system, resulting in
      venous hypertension. Venous hypertension is the cause of the most important
      symptoms of PTS: pain, oedema and skin abnormalities. Compression therapy reduces
      oedema and pain in patients in the acute phase following DVT. Based on convincing
      results from randomised trials, elastic compression therapy was recommended for
      patients with DVT for many years, in order to prevent venous hypertension and
      PTS. Recent studies have led to discussion on the added value of elastic
      compression.

PMID- 25990333
TI  - [Fever after visiting the tropics: always exclude malaria].
AB  - Malaria usually begins with nonspecific symptoms which could easily be ascribed
      to other common febrile illnesses and hence be missed. If left untreated, it can
      lead to severe complicated malaria and death. We describe a case of a 43-year-old
      male patient with fever who recently returned from West Africa. Initially he was
      treated for pneumonia; however, after 4 days his symptoms deteriorated and he was
      diagnosed with severe complicated falciparum malaria for which he was admitted to
      the ICU. We advocate prompt exclusion of malaria in every patient presenting with
      fever in the three months following return from an endemic region, and remaining
      vigilant for an extended period. 

PMID- 25990334
TI  - [Per-oral endoscopic myotomy in achalasia].
AB  - The treatment of patients with achalasia is complex due to a considerably high
      recurrence rate and risk of treatment-related complications. The per-oral
      endoscopic myotomy (POEM) is a new endoscopic technique that combines the
      benefits of a minimally invasive endoscopic procedure with the efficacy of a
      surgical myotomy. Implementation of the POEM technique may lead to fewer
      complications, a lower recurrence rate and reduced costs. During the procedure, a
      myotomy of the circular muscle layer of the oesophagus is performed after
      creating a submucosal tunnel in the oesophagus. The first studies of this new
      technique show promising results. Experienced therapeutic endoscopists can learn
      to perform the POEM technique relatively easily. Further studies are needed to
      compare this technique with the current standard treatments and to evaluate long
      term effects. 

PMID- 25990335
TI  - [Hereditary leiomyomatosis: a woman with red-brown nodules].
AB  - BACKGROUND: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare
      disorder involving multiple organ systems. It is caused by a mutation in the
      fumarate hydratase (FH) gene. Patients show cutaneous abnormalities or uterine
      myomas. Approximately 10% of these patients also develop an aggressive type of
      renal cell carcinoma. CASE DESCRIPTION: A 35-year-old woman was referred by her
      general practitioner with a number of progressive red-brown nodules on her arms
      and trunk. A biopsy was taken, revealing cutaneous leiomyoma. On further
      examination, a small, benign uterine myoma was found. There were no signs of a
      renal cell carcinoma. Further diagnostic procedures showed a FH mutation,
      confirming the diagnosis of HLRCC. CONCLUSION: HRLCC is a rare condition that can
      be missed easily as clinical symptoms are often subtle. Considering the risk of
      developing an aggressive form of renal cell carcinoma, it is important to screen
      these patients thoroughly and to follow them up.

PMID- 25990336
TI  - [Medication review in older people: identification of a new risk group].
AB  - The Dutch multidisciplinary guideline on 'Polypharmacy in older people' advises
      performing an annual medication review for patients aged 65 or older who use five
      or more drugs and have at least one risk factor for negative outcomes of their
      drug usage. We describe a 79-year-old male patient with an indication for a
      medication review and identified drug-related problems (DRPs). Furthermore, we
      describe two female patients aged 97 and 91 who use fewer than five drugs,
      dispensed via an automated system, and also have DRPs. We suggest adding the use
      of a multidose drug-dispensing system as an indication for a medication review.
      This will also help to identify patients with undertreatment. In addition, we
      recommend improving collaboration with pharmacists, which may enhance the effect
      of a medication review by increasing the number of drug changes. 

PMID- 25990337
TI  - [Treatment of lung cancer guided by genomic tumour profiles].
AB  - Lung cancer is a collection of rare diseases, each with its specific genomic
      abnormalities. Next generation sequencing is a novel diagnostic tool to discover
      driver mutations. This technology, together with the development of targeted
      drugs, is rapidly changing our understanding of lung cancer. KRAS gene mutations
      are the most common mutation in adenocarcinoma of the lung. Patients with ALK
      rearrangements treated with specific ALK inhibitors such as crizotinib or EGFR
      activating mutations treated with gefitinib, erlotinib or afatinib have improved
      progression-free survival and better quality of life than patients treated with
      chemotherapy. The latter may subsequently develop tumour resistance, for which
      novel drugs are rationally designed. In the Netherlands, multidisciplinary tumour
      boards guide the interpretation of genomic aberrations and the use of registered
      and off-label targeted drugs. 

PMID- 25990338
TI  - [The revised NHG guideline 'COPD': a new approach with old limitations].
AB  - In April 2015, the Dutch College of General Practitioners (NHG) published a
      revised version of its guideline on chronic obstructive pulmonary disease. The
      emphasis on a thorough evaluation of complaints and symptoms, in addition to the
      degree of airway obstruction, is new but the old limitations encountered in the
      treatment of patients with COPD remain in place. Real progress can only be made
      once we are genuinely able to control smoking or to influence the regenerative
      properties of the lung. 

PMID- 25990339
TI  - [The NHG guidelines 'Adult asthma' and 'COPD'].
AB  - The Dutch College of General Practitioners (NHG) guidelines 'Adult asthma' and
      'COPD' have been revised. New spirometry reference values from the Global Lung
      Function Initiative are recommended. Airway obstruction is defined as a FEV1/FVC
      ratio below the 5th percentile for the reference population. Spirometry for
      diagnosis takes place without use of patients' inhaled medication and consists of
      measurements before and after standardized bronchodilation. In monitoring
      spirometry, patients continue using inhaled medication and standardized
      bronchodilation is not indicated. The goal of asthma management is optimal asthma
      control, tailored to individual goals. The most important non-drug intervention
      in asthma and COPD is to recommend stopping smoking. The goal of COPD management
      is to limit symptoms, improve exercise capacity and quality of life, and reduce
      the burden of disease. Inhaled corticosteroids are usually not indicated in COPD
      treatment. Patients with comorbid asthma and COPD are treated with non-drug
      interventions according to the COPD guideline and with medication according to
      the asthma guideline.

PMID- 25990340
TI  - Prognostic Value of Body Mass Index According to Histologic Subtype in
      Nonmetastatic Renal Cell Carcinoma: A Large Cohort Analysis.
AB  - OBJECTIVE: The objective of our study was to assess the prognostic value of body
      mass index (BMI) according to histologic subtype in nonmetastatic renal cell
      carcinoma (RCC), based on a large multicenter experience. METHODS: A total of
      2769 patients with nonmetastatic RCC at the time of surgery were enrolled from 5
      Korean institutions between 1999 and 2011. BMI was used as a continuous variable
      and was categorized according to the World Health Organization recommendation for
      Asians into normal weight (>= 18.5 and < 23 kg/m(2)) and overweight and obese (>=
      23 kg/m(2)). RESULTS: In patients with clear cell variant, increased BMI was
      associated with higher recurrence-free survival (RFS) or cancer-specific survival
      (CSS) rates by multivariate analyses (hazard ratio [HR] of RFS, 0.940; P = .007;
      HR of CSS, 0.875; P < .001). On the other hand, increased BMI in patients with
      chromophobe variant was associated with lower RFS or CSS rates, unlike in
      patients with clear cell variant (HR of RFS, 1.317, P = .011; HR of CSS, 1.320; P
      = .031). In patients with papillary variant, BMI was not associated with RFS or
      CSS (P > .05 for each). CONCLUSIONS: Our results showed that increased BMI was a
      favorable prognostic factor in patients with clear cell variant. However,
      increased BMI was a poor prognostic factor in patients with chromophobe variant
      and was not associated with prognosis in those with papillary variant. Our study
      suggests that the association between BMI and RCC prognosis may differ by
      histologic subtype.

PMID- 25990341
TI  - Deep brain stimulation of the globus pallidus internus or ventralis intermedius
      nucleus of thalamus for Holmes tremor.
AB  - Holmes tremor (HT) is a difficult-to-treat, very disabling symptomatic condition
      which characteristically appears weeks to years after a brain lesion. It features
      a unique combination of rest, action, and postural tremors. Pharmacotherapy is
      mostly not effective. Chronic deep brain stimulation (DBS) of ventralis
      intermedius nucleus (Vim) of thalamus has been described as being the best
      surgical approach in singular case series; various authors observe, however,
      cases with partial responses only; therefore, alternatives are still needed. We
      report ten patients with HT unresponsive to best medical therapy who underwent
      DBS in our center from March 2002 to June 2012. Based in our previous experience
      dealing with cases of unsatisfactory Vim intraoperative tremor control and in
      order to optimize surgical results, presurgical target planning included two
      Nuclei: Vim and posteroventral Globus pallidus internus (GPi) (Espinoza et al.
      2010; Espinoza et al. Stereotact Funct Neurosurg 90(suppl 1):1-202, p 61, 2012).
      Definitive chosen target was decided after single-cell microelectrode recording,
      intraoperative test stimulation, thresholds for stimulation-induced adverse
      effects and best clinical response compared to baseline status. Fahn-Tolosa-Marin
      tremor rating scale (FTM-TRS) was used to evaluate outcome. The electrode was
      implanted in the nucleus with the best tremor suppression achievement; on the
      other hand, GPi DBS was initially decided if one of the following conditions was
      present: (a) If Vim nucleus anatomy was grossly altered; (b) when intraoperative
      tremor control was unsatisfactory despite Vim high-intensity stimulation; or (c)
      if unaffordable side effects or even tremor worsening occurred during
      intraoperative macrostimulation. Seven patients received definitive Gpi DBS
      implantation, while three patients received Vim DBS. In all observed cases, we
      observed an improvement on the TRS. In two cases where Vim thalamic anatomy was
      altered by the pathological insult GPI was planned from the beginning, and same
      was true in two additional cases where the Gpi nucleus showed major alterations
      allowing only Vim planning. Over all cases, the average improvement in tremor was
      of 2.55 points on the TRS or a 64 % increase in measured results; with a minimum
      of 1 point (25 %) improvement in one case and a maximum of 4 points (100 %
      improvement) also in one case. All the results were sustained at 2 years follow
      up. One case with predominant resting component, implanted in the GPi, achieved
      the maximum possible tremor reduction (from 4 to 0 points, meaning 100 % tremor
      reduction); in the nine resting cases, the average reduction was of 3 points (or
      75 %). DBS demonstrated in this case series adequate tremor control in 10
      patients unresponsive to medical therapy. Presurgical planning of two targets
      allowed choosing best optimal response. Gpi stimulation could be considered as an
      alternative target for cases in which thalamic anatomy is considerably altered or
      Vim intraoperative stimulation does not produce satisfactory results. 

PMID- 25990342
TI  - A prospective randomized evaluation of the TriGuardTM HDH embolic DEFLECTion
      device during transcatheter aortic valve implantation: results from the DEFLECT
      III trial.
AB  - AIMS: To evaluate the safety, efficacy, and performance of the TriGuardTM HDH
      Embolic Deflection Device (TriGuard) compared with no cerebral protection in
      patients undergoing transcatheter aortic valve implantation (TAVI). METHODS AND
      RESULTS: From February 2014 to March 2015, 85 subjects undergoing TAVI at 13
      centres in Europe and Israel were randomized to TriGuard protection vs. no
      protection. Subjects underwent neurologic and cognitive evaluation at baseline,
      pre-discharge and 30 days; cerebral diffusion-weighted magnetic resonance imaging
      was performed at 4 +/- 2 days post-procedure and at 30 days. Technical success,
      which included complete 3-vessel cerebral coverage, was achieved in 88.9% (40/45)
      of cases. The primary in-hospital procedural safety endpoint (death, stroke, life
      threatening or disabling bleeding, stage 2 or 3 acute kidney injury, or major
      vascular complications) occurred in 21.7% of TriGuard and 30.8% of control
      subjects (P = 0.34). In the Per Treatment population (subjects with complete
      three-vessel cerebral coverage), TriGuard use was associated with greater freedom
      from new ischaemic brain lesions (26.9 vs. 11.5%), fewer new neurologic deficits
      detected by the National Institutes of Health Stroke Scale (3.1 vs. 15.4%),
      improved Montreal Cognitive Assessment (MoCA) scores, better performance on a
      delayed memory task (P = 0.028) at discharge, and a >2-fold increase in recovery
      of normal cognitive function (MoCA score >26) at 30 days. CONCLUSION: TriGuard
      cerebral protection during TAVI is safe and complete cerebral vessel coverage was
      achieved in 89% of subjects. In this exploratory study, subjects undergoing
      protected TAVI had more freedom from ischaemic brain lesions, fewer neurologic
      deficits, and improved cognitive function in some domains at discharge and 30
      days compared with controls.

PMID- 25990343
TI  - Reflect on DEFLECT.

PMID- 25990344
TI  - Proceedings from the European clinical consensus conference for renal
      denervation: considerations on future clinical trial design.

PMID- 25990345
TI  - Exacerbation of cardiac energetic impairment during exercise in hypertrophic
      cardiomyopathy: a potential mechanism for diastolic dysfunction.
AB  - AIMS: Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac
      death in the young, with an excess of exercise-related deaths. The HCM sarcomere
      mutations increase the energy cost of contraction and impaired resting cardiac
      energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP)
      using (31)Phosphorus MR Spectroscopy ((31)P MRS). We hypothesized that cardiac
      energetics are further impaired acutely during exercise in HCM and that this
      would have important functional consequences. METHODS AND RESULTS: (31)P MRS was
      performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at
      rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular
      filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated
      during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM:
      1.71 +/- 0.35, normal 2.14 +/- 0.35 P < 0.0001). During exercise, there was a
      further reduction in PCr/ATP in HCM (1.56 +/- 0.29, P = 0.02 compared with rest)
      but not in normals (2.16 +/- 0.26, P = 0.98 compared with rest). There was no
      correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or
      late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at
      rest (r = 0.48, P = 0.02) and stress (r = 0.53, P = 0.01). CONCLUSION: During
      exercise, the pre-existing energetic deficit in HCM is further exacerbated
      independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in
      keeping with the change at the myofilament level. We offer a potential
      explanation for exercise-related diastolic dysfunction in HCM.

PMID- 25990346
TI  - Positive margins after local excision of early rectal cancer: a dedicated
      multidisciplinary team.

PMID- 25990347
TI  - An Unusual Case of Double-Orifice Mitral Valve Associated with D-Transposition of
      Great Arteries and Left-Side Heart Anomalies.

PMID- 25990348
TI  - Proteins that bind regulatory regions identified by histone modification
      chromatin immunoprecipitations and mass spectrometry.
AB  - The locations of transcriptional enhancers and promoters were recently mapped in
      many mammalian cell types. Proteins that bind those regulatory regions can
      determine cell identity but have not been systematically identified. Here we
      purify native enhancers, promoters or heterochromatin from embryonic stem cells
      by chromatin immunoprecipitations (ChIP) for characteristic histone modifications
      and identify associated proteins using mass spectrometry (MS). 239 factors are
      identified and predicted to bind enhancers or promoters with different levels of
      activity, or heterochromatin. Published genome-wide data indicate a high accuracy
      of location prediction by ChIP-MS. A quarter of the identified factors are
      important for pluripotency and includes Oct4, Esrrb, Klf5, Mycn and Dppa2,
      factors that drive reprogramming to pluripotent stem cells. We determined the
      genome-wide binding sites of Dppa2 and find that Dppa2 operates outside the
      classical pluripotency network. Our ChIP-MS method provides a detailed read-out
      of the transcriptional landscape representative of the investigated cell type. 

PMID- 25990349
TI  - A rapid and accurate method for the quantitative estimation of natural
      polysaccharides and their fractions using high performance size exclusion
      chromatography coupled with multi-angle laser light scattering and refractive
      index detector.
AB  - In this study, a rapid and accurate method for quantitative analysis of natural
      polysaccharides and their different fractions was developed. Firstly, high
      performance size exclusion chromatography (HPSEC) was utilized to separate
      natural polysaccharides. And then the molecular masses of their fractions were
      determined by multi-angle laser light scattering (MALLS). Finally, quantification
      of polysaccharides or their fractions was performed based on their response to
      refractive index detector (RID) and their universal refractive index increment
      (dn/dc). Accuracy of the developed method for the quantification of individual
      and mixed polysaccharide standards, including konjac glucomannan, CM-arabinan,
      xyloglucan, larch arabinogalactan, oat beta-glucan, dextran (410, 270, and 25
      kDa), mixed xyloglucan and CM-arabinan, and mixed dextran 270 K and CM-arabinan
      was determined, and their average recoveries were between 90.6% and 98.3%. The
      limits of detection (LOD) and quantification (LOQ) were ranging from 10.68 to
      20.25 MUg/mL, and 42.70 to 68.85 MUg/mL, respectively. Comparing to the
      conventional phenol sulfuric acid assay and HPSEC coupled with evaporative light
      scattering detection (HPSEC-ELSD) analysis, the developed HPSEC-MALLS-RID method
      based on universal dn/dc for the quantification of polysaccharides and their
      fractions is much more simple, rapid, and accurate with no need of individual
      polysaccharide standard, as well as free of calibration curve. The developed
      method was also successfully utilized for quantitative analysis of
      polysaccharides and their different fractions from three medicinal plants of
      Panax genus, Panax ginseng, Panax notoginseng and Panax quinquefolius. The
      results suggested that the HPSEC-MALLS-RID method based on universal dn/dc could
      be used as a routine technique for the quantification of polysaccharides and
      their fractions in natural resources.

PMID- 25990350
TI  - The use of immunoaffinity columns connected in tandem for selective and cost
      effective mycotoxin clean-up prior to multi-mycotoxin liquid chromatographic
      tandem mass spectrometric analysis in food matrices.
AB  - This paper describes the use of two immunoaffinity columns (IACs) coupled in
      tandem, providing selective clean-up, based on targeted mycotoxins known to co
      occur in specific matrices. An IAC for aflatoxins+ochratoxin A+fumonisins (AOF)
      was combined with an IAC for deoxynivalenol+zearalenone+T-2/HT-2 toxins (DZT); an
      IAC for ochratoxin A (O) was combined with a DZT column; and an
      aflatoxin+ochratoxin (AO) column was combined with a DZT column. By combining
      pairs of columns it was demonstrated that specific clean-up can be achieved as
      required for different matrices. Samples of rye flour, maize, breakfast cereal
      and wholemeal bread were analysed for mycotoxins regulated in the EU, by spiking
      at levels close to EU limits for adult and infant foods. After IAC clean-up
      extracts were analysed by LC-MS/MS with quantification using multiple reaction
      monitoring. Recoveries were found to be in range from 60 to 108%, RSDs below 10%
      depending on the matrix and mycotoxin combination and LOQs ranged from 0.1n g/g
      for aflatoxin B1 to 13.0 ng/g for deoxynivalenol. Surplus cereal proficiency test
      materials (FAPAS((r))) were also analysed with found levels of mycotoxins falling
      within the satisfactory range of concentrations (Z score <= +/- 2), demonstrating
      the accuracy of the proposed multi-mycotoxin IAC methods.

PMID- 25990351
TI  - beta-cyclodextrin functionalized meso-/macroporous magnetic titanium dioxide
      adsorbent as extraction material combined with gas chromatography-mass
      spectrometry for the detection of chlorobenzenes in soil samples.
AB  - A high-performance and selective adsorbent was developed for simultaneous
      extraction of 6 chlorobenzenes residues in soil samples by using magnetic solid
      phase extraction (MSPE) combined with automated SPE followed by gas
      chromatography-mass spectrometry (GC-MS). The adsorbent was synthesized by
      grafting carboxymethyl-beta-cyclodextrin (CM-beta-CD) on the surface of porous
      core-shell magnetic Fe3O4@flower like TiO2 microspheres (Fe3O4@fTiO2-CMCD), used
      as a carrier. The main factors (adsorbent amount, adsorption time, elution
      solvent, elution volume, and elution flow rate) affecting the extraction
      efficiency were investigated in detail. The adsorbent exhibited high loading
      capacity (25.6 mg g(-1) for 1,3-dichlorobenzene). This maybe due to meso
      /macroporous TiO2 having high specific surface area; as a carrier of the beta
      cyclodextrin film, it could obviously increase the number of recognition sites.
      The newly developed adsorbent also showed good selectivity towards chlorobenzenes
      based on host-guest interactions between beta-cyclodextrin (on adsorbent's
      surface) and targets, which can minimize complex matrix interference in soil
      samples. The proposed method was successfully applied for the analysis of
      environmental soil samples with recovery ranging from 87.3 to 104.3%. All target
      compounds showed good linearities with correlation coefficients (r) higher than
      0.996. The limits of quantitation for the 6 CBs were 0.03-0.09 MUg kg(-1). These
      findings confirmed meso-/macroporous structure Fe3O4@fTiO2-CMCD as a highly
      effective extraction material for use in trace CB analyses in complex soil
      samples.

PMID- 25990352
TI  - Methodology of motor evoked potentials in a rabbit model.
AB  - Spinal cord ischemia (SCI) is a devastating complication of aortic operations.
      Neuromonitoring using motor evoked potentials (MEPs) is a sensitive modality to
      detect SCI in humans. We describe a leporine SCI model using MEPs to test
      pharmaceutical therapeutics and other neuroprotective adjuncts. In 80 rabbits,
      methods to obtain MEPs in normotensive and ischemic rabbits were developed. The
      effects of isoflurane, propofol, apnea, and hypotension on lower extremity MEPs
      were studied. Lower extremity MEPs disappear upon SCI induction in 78 of 78 (100
      %) rabbits. Prior to SCI induction and during apneic episodes, lower extremity
      MEPs were lost in all (100 %) and upper extremity MEPs in one (25 %). Isoflurane
      was used in four experiments, with loss of lower extremity MEPs in all four (100
      %) and loss of upper extremity MEPs in zero. With propofol upper extremity, MEPs
      were obtainable in 80 of 80 rabbits (100 %) and lower extremity MEPs in 78 of 80
      rabbits (97.5 %) prior to SCI induction. The presence of these lower extremity
      MEPs prior to SCI induction was not correlated with systolic or diastolic blood
      pressure. Disappearance of MEPs occurred in all 45 rabbits with postoperative
      lower extremity impairment. MEPs in the leporine model correlate closely with
      paraplegia. MEPs are influenced by inhaled anesthetics and apnea but not by
      hypotension alone. Propofol anesthesia provides reliable MEPs. This study
      provides the basis for a reproducible model of SCI to be used for novel
      therapeutic drug development. 

PMID- 25990353
TI  - Androgen deprivation increases the risk of fracture in prostate cancer patients:
      a population-based study in Chinese patients.
AB  - Androgen deprivation therapy (ADT) or orchiectomy is associated with an increased
      risk of osteoporosis or fracture. In this nationwide database analysis, we found
      that ADT or orchiectomy increased the risk of fracture in Chinese patients with
      prostate cancer. However, the magnitude of increase is seemingly not as large as
      that in Western populations. INTRODUCTION: ADT using gonadotropin-releasing
      hormone (GnRH) agonists or orchiectomy is associated with an increased risk of
      osteoporosis or fracture. To investigate the effects of ADT duration or
      orchiectomy on any type of fracture in Asian patients with prostate cancer, we
      conducted this retrospective analysis using a nationwide database in Taiwan.
      METHODS: We included 17,359 subjects who were newly diagnosed with prostate
      cancer between January 1, 1998, and December 31, 2007. The risk of first fracture
      was our primary endpoint. RESULTS: The rates of fracture from 12 months after
      prostate cancer diagnosis until the last follow-up date were 8.7 % for all
      patients, 7.1 % for patients who did not receive ADT or orchiectomy, 9.8 % for
      patients who received ADT, and 14.4 % for patients who received orchiectomy with
      or without ADT (P < 0.0001). In a Cox proportional hazard analysis, the relative
      risk of fracture increased steadily with the number of doses of GnRH agonists
      received during the first year after cancer diagnosis and with dose density. A
      significant hazard ratio was observed in patients who received at least nine
      doses within 1 year after diagnosis and in those whose dose density exceeded two
      doses per year. Age greater than or equal to 65 years was associated with a
      significantly lower risk of fracture. CONCLUSION: ADT or orchiectomy increases
      the risk of fracture in Chinese patients with prostate cancer. However, the
      magnitude of this increase is seemingly not as large as that in Western
      populations.

PMID- 25990354
TI  - Response of bone turnover markers to three oral bisphosphonate therapies in
      postmenopausal osteoporosis: the TRIO study.
AB  - We used bone turnover markers to identify women who responded to bisphosphonate
      treatment for osteoporosis. Response was more likely with alendronate and
      ibandronate than risedronate. There was a greater decrease in bone markers if
      baseline bone turnover markers were higher and if the patient took more than 80 %
      of her medication. INTRODUCTION: Biochemical response to bisphosphonate therapy
      can be assessed using either a decrease in bone turnover marker beyond the least
      significant change (LSC) or a reduction to within a reference interval (RI). We
      compared the performance of these target responses and determined whether
      response was related to the type of bisphosphonate, compliance and baseline bone
      turnover markers. METHODS: Biochemical responses to three oral bisphosphonates
      were assessed in an open, controlled trial comprising 172 postmenopausal
      osteoporotic women (age 53-84 years), randomised to alendronate, ibandronate or
      risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for
      each marker was derived within the study population, whereas RIs were obtained
      from a control group of healthy premenopausal women (age 35-40 years). RESULTS:
      Over 70 % of women achieved a target response for serum CTX and PINP,
      irrespective of the approach used. The percentage decrease at 12 weeks was
      greater for women with baseline PINP above the RI -63 % (difference 13 %, 95 % CI
      0 to 27.1, P = 0.049) and good compliance -67 % (difference 15.9 %, 95 % CI 6.3
      to 25.5, P = 0.001). Responders had a greater increase in spine bone density
      compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI
      1.6 to 6.3, P = 0.0011) for PINP LSC. The magnitude of change in bone markers was
      greater with ibandronate and alendronate than risedronate. CONCLUSIONS: Both
      approaches to response identified similar proportions of women as responders.
      Nonresponders had smaller increases in BMD, and we suggest that biochemical
      assessment of response is a useful tool for the management of women with
      postmenopausal osteoporosis.

PMID- 25990356
TI  - The microbiological quality of water in fish spas with Garra rufa fish, the
      Netherlands, October to November 2012.
AB  - In fish spas, clients may submerge their hands, feet or whole body in basins with
      Garra rufa fish, for dead skin removal. Skin infections may result from using
      these spas, transmitted from fish to clients, through either fish or water, or
      from client to client. The microbiological water quality was determined in 24
      fish spas in 16 companies in the Netherlands through analysis of a single water
      sample per fish spa. Water samples were tested for the presence of Aeromonas
      spp., Vibrio spp.,Pseudomonas aeruginosa, nontuberculous mycobacteria,and faecal
      indicator bacteria by using standard culture methods. The majority of the
      examined fish spas contained Aeromonas spp. (n = 24), P. aeruginosa(n = 18),
      Vibrio spp. (n = 16) including V. cholerae non-O1/O139 and V. vulnificus, and
      several rapid growing Mycobacterium spp. (n = 23) including M. fortuitum,
      M.conceptionense, M. abscessus and M. chelonae. Faecal contamination of the fish
      spa water was low. Based on the detected concentrations of Aeromonas spp.,
      Vibriospp., and P. aeruginosa, the detected Mycobacteriumspp., and the health
      implications of these bacteria, the health risk from using fish spas is
      considered limited for healthy people with an intact skin and no underlying
      disease.

PMID- 25990355
TI  - Denosumab versus zoledronic acid in patients previously treated with zoledronic
      acid.
AB  - Denosumab and zoledronic acid are potent antiresorptives. In this study in
      patients pre-treated with zoledronic acid, denosumab achieved similar increases
      with zoledronic acid in lumbar spine BMD despite the more prominent reduction of
      bone turnover markers. Denosumab reversibly reduced endogenous RANKL.
      INTRODUCTION: We aimed to compare yearly changes in lumbar spine (LS) bone
      mineral density (BMD), bone turnover markers, free soluble receptor activator of
      nuclear factor kappaB ligand (sRANKL) and sclerostin levels between denosumab and
      zoledronic acid. METHODS: Postmenopausal women with low bone mass previously
      treated with zoledronic acid for 1 year were assigned to denosumab injection (n =
      32) or zoledronic acid infusion (n = 26). Procollagen type 1 N-terminal
      propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx),
      sRANKL, and sclerostin levels were measured in serum samples obtained at baseline
      and 3, 6, and 12 months after denosumab injection or zoledronic acid infusion. LS
      BMD was measured at baseline and 12 months. RESULTS: The mean LS increase was 4.5
      and 4.4% with denosumab and zoledronic acid, respectively (p = 0.560). Denosumab
      caused a larger decrease in CTx at 3 months (p < 0.001) and P1NP at 3 (p <
      0.001), 6 (p = 0.021), and 12 months (p = 0.042). Denosumab significantly
      decreased sRANKL by 87.4% at 3 months (p < 0.001). Sclerostin levels were not
      changed with either intervention (p = 0.162 and p = 0.214, respectively).
      CONCLUSIONS: In patients previously treated with zoledronic acid, denosumab
      reduces bone turnover more than zoledronic acid, but the increases in LS BMD are
      comparable. Furthermore, denosumab administration results in reversible
      inhibition of the metabolically significant endogenous free soluble RANKL levels.
      Serum sclerostin is not affected by either agent.

PMID- 25990357
TI  - Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of
      tularaemia in Norway, 2011.
AB  - In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded
      cases. It was associated with the largest peak in lemming density seen in 40
      years. Francisella tularensis was isolated from 18 patients. To study the
      geographical distribution of F.tularensis genotypes in Norway and correlate
      genotype with epidemiology and clinical presentation,we performed whole genome
      sequencing of patient isolates. All 18 genomes from the outbreak carried genetic
      signatures of F. tularensis subsp. holarctica and were assigned to genetic clades
      using canonical single nucleotide polymorphisms. Ten isolates were assigned to
      major genetic clade B.6 (subclade B.7),seven to clade B.12, and one to clade B.4.
      The B.6 subclade B.7 was most common in southern and central Norway, while clade
      B.12 was evenly distributed between the southern, central and northern parts of
      the country. There was no association between genotype and clinical presentation
      of tularaemia, time of year or specimen type. We found extensive sequence
      similarity with F. tularensis subsp. holarctica genomes from high-endemic
      tularaemia areas in Sweden.Finding nearly identical genomes across large
      geographical distances in Norway and Sweden imply a life cycle of the bacterium
      without replication between the outbreaks and raise new questions about long
      range migration mechanisms.

PMID- 25990358
TI  - Illness and injury of travellers abroad: Finnish nationwide data from 2010 to
      2012, with incidences in various regions of the world.
AB  - The number of international tourist arrivals reached 1,000 million in 2012.
      Assessment of travellers' health problems has relied on proportionate morbidity
      data.Given the lack of data on number of visitors to each region, incidences have
      been impossible to calculate.This study, largest yet reporting travellers' health
      problems, is the first to present incidence of illness and injury. Data on
      Finnish travellers with health problems abroad during 2010 to 2012 were retrieved
      from the database of an assistance organisation,SOS International, covering 95%
      of those requiring aid abroad. The numbers were compared with those of Finnish
      travellers in the database of the Official Statistics of Finland. The SOS
      International database included 50,710 cases: infections constituted the most
      common health problem (60%), followed by injuries(14%), diseases of skin (5%),
      musculoskeletal system and connective tissue (5%), digestive tract (3%),and
      vascular system (2%). Gastroenteritis (23%) and respiratory infections (21%)
      proved the most frequent diagnoses. Overall incidence of illness or injury was
      high in Africa (97.9/100,000 travel days; 95% Bayesian credible interval (BCI):
      53.1-145.5), southern Europe plus the eastern Mediterranean (92.3; 95% BCI: 75.4
      110.1) and Asia (65.0; 95% BCI: 41.5-87.9). The data show significant differences
      between geographical regions, indicating the main risks and thus providing
      destination-specific tools for travelers' healthcare.

PMID- 25990359
TI  - Seroprevalence in blood donors reveals widespread, multi-source exposure to
      hepatitis E virus, southern France, October 2011.
AB  - The apparent seroprevalence of hepatitis E Virus (HEV)varies greatly among
      developed countries depending on the geographical area and the sensitivity of
      immunoassays. We used a validated assay to determine the prevalence of HEV IgG
      and IgM antibodies among 3,353 blood donors living in southern France,who gave
      blood during the two first weeks of October 2011 and participated in the study.
      Demographic and epidemiological information was collected using aspecific
      questionnaire. We also screened 591 samples for HEV RNA. Overall IgG
      seroprevalence was 39.1%and varied from 20% to 71.3% depending on the
      geographical area (p < 0.001) while IgM seroprevalence was 3.31%. Anti-HEV IgG
      was significantly correlated with increasing age (p < 0.001), eating uncooked
      pork liver sausages (p < 0.001), offal (p = 0.003), or mussels(p = 0.02). Anti
      HEV IgM was associated with being male (p = 0.01) and eating uncooked pork liver
      sausages(p = 0.02). HEV RNA was detected in one of the 99 anti-HEV IgM-positive
      samples, but in none of the 492 anti-HEV IgM-negative samples. HEV is
      hyperendemic in southern France. Dietary and culinary habits alone cannot explain
      the epidemiology of HEV in this region, indicating that other modes of
      contamination should be investigated.

PMID- 25990360
TI  - Ten years experience of syndromic surveillance for civil and military public
      health, France, 2004-2014.

PMID- 25990362
TI  - Cameron's pledge on seven day working is branded "empty headline grabbing".

PMID- 25990361
TI  - Carbapenems Versus Piperacillin-Tazobactam for Bloodstream Infections of
      Nonurinary Source Caused by Extended-Spectrum Beta-Lactamase-Producing
      Enterobacteriaceae.
AB  - A recent, frequently quoted study has suggested that for bloodstream infections
      (BSIs) due to extended-spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBL) Escherichia coli, treatment with beta-lactam/beta-lactamase inhibitors
      (BLBLIs) might be equivalent to treatment with carbapenems. However, the majority
      of BSIs originate from the urinary tract. A multicenter, multinational efficacy
      analysis was conducted from 2010 to 2012 to compare outcomes of patients with non
      urinary ESBL BSIs who received a carbapenem (69 patients) vs those treated with
      piperacillin-tazobactam (10 patients). In multivariate analysis, therapy with
      piperacillin-tazobactam was associated with increased 90-day mortality (adjusted
      odds ratio, 7.9, P=.03). For ESBL BSIs of a non-urinary origin, carbapenems
      should be considered a superior treatment to BLBLIs.

PMID- 25990363
TI  - Root contact responses and the positive relationship between intraspecific
      diversity and ecosystem productivity.
AB  - High species and functional group richness often has positive effects on
      ecosystem function including increasing productivity. Recently, intraspecific
      diversity has been found to have similar effects, but because traits vary far
      less within a species than among species we have a much poorer understanding of
      the mechanisms by which intraspecific diversity affects ecosystem function. We
      explored the potential for identity recognition among the roots of different
      Pseudoroegneria spicata accessions to contribute to previously demonstrated
      overyielding in plots with high intraspecific richness of this species relative
      to monocultures. First, we found that when plants from different populations were
      planted together in pots the total biomass yield was 30 % more than in pots with
      two plants from the same population. Second, we found that the elongation rates
      of roots of Pseudoroegneria plants decreased more after contact with roots from
      another plant from the same population than after contact with roots from a plant
      from a different population. These results suggest the possibility of some form
      of detection and avoidance mechanism among more closely related Pseudoroegneria
      plants. If decreased growth after contact results in reduced root overlap, and
      reduced root overlap corresponds with reduced growth and productivity, then
      variation in detection and avoidance among related and unrelated accessions may
      contribute to how ecotypic diversity in Pseudoroegneria increases productivity. 

PMID- 25990364
TI  - Ion homeostasis in a salt-secreting halophytic grass.
AB  - Salinity adversely affects plant growth and development, and disturbs
      intracellular ion homeostasis, resulting in cellular toxicity. Plants that
      tolerate salinity, halophytes, do so by manifesting numerous physiological and
      biochemical processes in coordination to alleviate cellular ionic imbalance. The
      present study was undertaken to analyse the salt tolerance mechanism in Aeluropus
      lagopoides (L.) trin. Ex Thw. (Poaceae) at both physiological and molecular
      levels. Plants secreted salt from glands, which eventually produced pristine salt
      crystals on leaves and leaf sheaths. The rate of salt secretion increased with
      increasing salt concentration in the growth medium. Osmotic adjustment was mainly
      achieved by inorganic osmolytes (Na(+)) and at 100 mM NaCl no change was observed
      in organic osmolytes in comparison to control plants. At 300 mM NaCl and with 150
      mM NaCl + 150 mM KCl, the concentration of proline, soluble sugars and amino
      acids was significantly increased. Transcript profiling of transporter genes
      revealed differential spatial and temporal expressions in both shoot and root
      tissues in a manner synchronized towards maintaining ion homeostasis. In shoots,
      AlHKT2;1 transcript up-regulation was observed at 12 and 24 h in all the
      treatments, whereas in roots, maximum induction was observed at 48 h with K(+)
      starvation. The HAK transcript was relatively abundant in shoot tissue with all
      the treatments. The plasma membrane Na(+)/H(+) antiporter, SOS1, and tonoplast
      Na(+)/H(+) antiporter, NHX1, were found to be significantly up-regulated in shoot
      tissue. Our data demonstrate that AlHKT2;1, HAK, SOS1, NHX1 and V-ATPase genes
      play a pivotal role in regulating the ion homeostasis in A. lagopoides. 

PMID- 25990365
TI  - Design of ultrasensitive DNA-based fluorescent pH sensitive nanodevices.
AB  - Here we tune the pH sensitivity of a DNA-based conformational switch, called the
      I-switch, to yield a set of fluorescent pH sensitive nanodevices with a
      collective, expanded pH sensing regime from 5.3 to 7.5. The expanded pH regime of
      this new family of I-switches originates from a dramatic improvement in the
      overall percentage signal change in response to pH of these nanodevices. 

PMID- 25990366
TI  - Ambulatory arterial stiffness index and carotid intima-media thickness in
      hypertensive rheumatoid patients: a comparative cross-sectional study.
AB  - AIM: Rheumatoid arthritis is associated with accelerated atherosclerosis.
      However, little is known about preclinical atherosclerosis in hypertensive
      rheumatoid arthritis patients. In this cross-sectional study we assessed the
      expression of preclinical atherosclerosis in hypertensive rheumatoid arthritis
      patients in comparison with matched hypertensive non-rheumatoid arthritis
      patients. METHODS: The study included 52 hypertensive rheumatoid arthritis
      patients and 42 hypertensive non-rheumatoid arthritis patients. The patients were
      extensively examined clinically and laboratory tested. The expression of
      preclinical atherosclerosis was estimated by assessing ambulatory arterial
      stiffness index and common carotid intima-media thickness. RESULTS: Arterial
      stiffness index and common carotid intima-media thickness were higher in
      hypertensive rheumatoid arthritis patients than in hypertensive non-rheumatoid
      arthritis patients. There was no correlation between arterial stiffness index and
      common carotid intima-media thickness with markers of inflammation and disease
      activity in hypertensive rheumatoid arthritis patients. CONCLUSION: The
      expression of subclinical atherosclerosis is more pronounced in hypertensive
      rheumatoid arthritis than in hypertensive non- rheumatoid arthritis patients.

PMID- 25990367
TI  - Changes in erectile organ structure and function in a rat model of chronic
      prostatitis/chronic pelvic pain syndrome.
AB  - There is a growing recognition of the association between chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED);
      however, most of the reports are based on questionnaires which cannot distinguish
      between organic and functional ED. The purpose of this study was to determine the
      exact relationship between CP/CPPS and ED, and to investigate the changes in
      erectile organ structure and function in a rat model of CP/CPPS. We established a
      rat model of experimental autoimmune prostatitis (EAP), which is a valid model
      for CP/CPPS. Erectile function in EAP and normal rats was comparable after
      cavernous nerve electrostimulation. The serum testosterone and oestradiol levels,
      ultrastructure of the corpus cavernosum and expression of endothelial nitric
      oxide synthase and neuronal nitric oxide synthase in the two groups were similar;
      however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth
      muscle actin expression and an increase in transforming growth factor-beta 1
      expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats.
      We speculate that ED complained by patients with CP/CPPS may be psychological,
      which could be caused by impairment in the quality of life; however, further
      studies are needed to fully understand the potential mechanisms underlying the
      penile fibrosis in EAP rats. 

PMID- 25990369
TI  - Molecular signature of salivary gland tumors: potential use as diagnostic and
      prognostic marker.
AB  - Salivary gland tumors are a highly heterogeneous group of lesions with diverse
      microscopic appearances and variable clinical behavior. The use of clinical and
      histological parameters to predict patient prognosis and survival rates has been
      of limited utility, and the search for new biomarkers that could not only aid in
      a better understanding of their pathogenesis but also be reliable auxiliaries for
      prognostic determination and useful diagnostic tools has been performed in the
      last decades with very exciting results. Hence, gene rearrangements such as CRTC1
      MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more
      than that, it has been strongly correlated with low-grade tumors and consequently
      with an increased survival rate and better prognosis of patients affected by
      neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene
      fusions were shown to be specifically found in cases of adenoid cystic carcinomas
      and hyalinizing clear cell carcinomas, respectively, in the context of salivary
      gland tumors, becoming reliable diagnostic tools for these entities and potential
      therapeutic targets for future therapeutic protocols. Finally, the identification
      of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas,
      cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the
      characterization of a completely new and now widely accepted entity, including,
      therefore, mammary analogue secretory carcinoma in the list of well-recognized
      salivary gland carcinomas. Thus, further molecular investigations of salivary
      gland tumors are warranted, and the recognition of other genetic abnormalities
      can lead to the acknowledgment of new entities and the acquirement of reliable
      biomarkers. 

PMID- 25990368
TI  - Acquisition of epithelial-mesenchymal transition phenotype in the tamoxifen
      resistant breast cancer cell: a new role for G protein-coupled estrogen receptor
      in mediating tamoxifen resistance through cancer-associated fibroblast-derived
      fibronectin and beta1-integrin signaling pathway in tumor cells.
AB  - INTRODUCTION: Acquired tamoxifen resistance remains the major obstacle to breast
      cancer endocrine therapy. beta1-integrin was identified as one of the target
      genes of G protein-coupled estrogen receptor (GPER), a novel estrogen receptor
      recognized as an initiator of tamoxifen resistance. Here, we investigated the
      role of beta1-integrin in GPER-mediated tamoxifen resistance in breast cancer.
      METHODS: The expression of beta1-integrin and biomarkers of epithelial
      mesenchymal transition were evaluated immunohistochemically in 53 specimens of
      metastases and paired primary tumors. The function of beta1-integrin was
      investigated in tamoxifen-resistant (MCF-7R) subclones, derived from parental MCF
      7 cells, and MCF-7R beta1-integrin-silenced subclones in MTT and Transwell
      assays. Involved signaling pathways were identified using specific inhibitors and
      Western blotting analysis. RESULTS: GPER, beta1-integrin and mesenchymal
      biomarkers (vimentin and fibronectin) expression in metastases increased compared
      to the corresponding primary tumors; a close expression pattern of beta1-integrin
      and GPER were in metastases. Increased beta1-integrin expression was also
      confirmed in MCF-7R cells compared with MCF-7 cells. This upregulation of beta1
      integrin was induced by agonists of GPER and blocked by both antagonist and
      knockdown of it in MCF-7R cells. Moreover, the epidermal growth factor
      receptor/extracellular regulated protein kinase (EGFR/ERK) signaling pathway was
      involved in this transcriptional regulation since specific inhibitors of these
      kinases also reduced the GPER-induced upregulation of beta1-integrin.
      Interestingly, silencing of beta1-integrin partially rescued the sensitivity of
      MCF-7R cells to tamoxifen and the alpha5beta1-integrin subunit is probably
      responsible for this phenomenon. Importantly, the cell migration and epithelial
      mesenchymal transition induced by cancer-associated fibroblasts, or the product
      of cancer-associated fibroblasts, fibronectin, were reduced by knockdown of beta1
      integrin in MCF-7R cells. In addition, the downstream kinases of beta1-integrin
      including focal adhesion kinase, Src and AKT were activated in MCF-7R cells and
      may be involved in the interaction between cancer cells and cancer-associated
      fibroblasts. CONCLUSIONS: GPER/EGFR/ERK signaling upregulates beta1-integrin
      expression and activates downstream kinases, which contributes to cancer
      associated fibroblast-induced cell migration and epithelial-mesenchymal
      transition, in MCF-7R cells. GPER probably contributes to tamoxifen resistance
      via interaction with the tumor microenvironment in a beta1-integrin-dependent
      pattern. Thus, beta1-integrin may be a potential target to improve anti-hormone
      therapy responses in breast cancer patients.

PMID- 25990371
TI  - Solution plasma synthesis of Si nanoparticles.
AB  - Silicon nanoparticles (Si-NPs) were directly synthesized from a Si bar electrode
      via a solution plasma. In order to produce smaller Si-NPs, the effects of
      different electrolytes and applied voltages on the product were investigated in
      the experiments detailed in this paper. The results demonstrated that the use of
      an acidic solution of 0.1 M HCl or HNO3 produced Si-NPs without SiO2 formation.
      According to the transmission electron microscopy and electron energy-loss
      spectroscopy, the obtained Si-NPs contained both amorphous and polycrystalline Si
      particles, among which the smaller Si-NPs tended to be amorphous. When an
      alkaline solution of K2CO3 was used instead, amorphous SiO2 particles were
      synthesized owing to the corrosion of Si in the high-temperature environment. The
      pH values of KCl and KNO3 increased during electrolysis, and the products were
      partially oxidized in the alkaline solutions. The particle size increased with an
      increasing applied voltage because the excitation temperature of the plasma
      increased. 

PMID- 25990370
TI  - Transient Increased Calcium and Calcitriol Requirements After Discontinuation of
      Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in
      Hypoparathyroidism.
AB  - Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism
      maintains eucalcemia and converts quiescent bone to high-turnover bone. However,
      the skeletal and metabolic effects of drug discontinuation have not been
      reported. Nine subjects with hypoparathyroidism received subcutaneous injections
      of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then
      transitioned back to calcium and calcitriol. Biochemistries and bone mineral
      density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at
      baseline, while on treatment, and at follow-up 3 to 12 months after drug
      discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly
      discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH
      1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two
      to three times pretreatment doses of calcitriol and calcium to maintain blood
      calcium levels. Doses were gradually reduced over many weeks until calcium levels
      were stable on doses similar to baseline. Bone-specific alkaline phosphatase
      (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with
      hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still
      slightly elevated. During treatment, BMD was unchanged at the hip and lateral
      spine but declined at the anterior-posterior (AP) spine, radius, and total body.
      During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH
      1-34 values and the whole body returning to baseline. AP spine was increased non
      significantly compared to baseline at follow-up. hPTH 1-34 must be gradually
      weaned in hypoparathyroid patients with high doses of oral medications given to
      avoid hypocalcemia. The transient increased requirements accompanied by increased
      BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded
      remodeling space favoring bone formation as the skeleton returns to a low
      turnover state, reminiscent of the hungry bone syndrome. Further study and close
      monitoring is required to ensure safe transition to conventional therapy and to
      elucidate the physiological mechanism of this phenomenon.

PMID- 25990372
TI  - Pollen S-locus F-box proteins of Petunia involved in S-RNase-based self
      incompatibility are themselves subject to ubiquitin-mediated degradation.
AB  - Many flowering plants show self-incompatibility, an intra-specific reproductive
      barrier by which pistils reject self-pollen to prevent inbreeding and accept non
      self pollen to promote out-crossing. In Petunia, the polymorphic S-locus
      determines self/non-self recognition. The locus contains a gene encoding an S
      RNase, which controls pistil specificity, and multiple S-locus F-box (SLF) genes
      that collectively control pollen specificity. Each SLF is a component of an SCF
      (Skp1/Cullin/F-box) complex that is responsible for mediating degradation of non
      self S-RNase(s), with which the SLF interacts, via the ubiquitin-26S proteasome
      pathway. A complete set of SLFs is required to detoxify all non-self S-RNases to
      allow cross-compatible pollination. Here, we show that SLF1 of Petunia inflata is
      itself subject to degradation via the ubiquitin-26S proteasome pathway, and
      identify an 18 amino acid sequence in the C-terminal region of S2 -SLF1 (SLF1 of
      S2 haplotype) that contains a degradation motif. Seven of the 18 amino acids are
      conserved among all 17 SLF proteins of S2 haplotype and S3 haplotype involved in
      pollen specificity, suggesting that all SLF proteins are probably subject to
      similar degradation. Deleting the 18 amino acid sequence from S2 -SLF1 stabilized
      the protein but abolished its function in self-incompatibility, suggesting that
      dynamic cycling of SLF proteins is an integral part of their function in self
      incompatibility. 

PMID- 25990373
TI  - A systematic narrative review of support groups for people with dementia.
AB  - BACKGROUND: Provision of non-pharmacological interventions is a common policy
      objective for people with dementia, and support groups are an increasingly common
      intervention. However, there have been few attempts to synthesize evidence on the
      effectiveness of support groups for people with dementia. This review
      investigated the outcomes of support groups for people with dementia, explored
      participant characteristics and reviewed group formats. METHODS: A systematic
      review was undertaken and a narrative synthesis of data from 29 papers (reporting
      on 26 groups and a survey of a range of groups) was conducted. RESULTS: Support
      groups seem acceptable to people with dementia. Qualitative studies report
      subjective benefits for participants but there is limited evidence of positive
      outcomes based on quantitative data. Samples have tended to be homogenous and
      this may limit the generalizability of findings. CONCLUSIONS: Although
      qualitative studies will remain important in this area, further mixed-methods
      randomized controlled trials (RCTs)or comparison group studies with longer follow
      up periods are needed to strengthen the evidence base.

PMID- 25990374
TI  - Quantitative evaluation of residual bony impingement lesions after arthroscopic
      treatment for isolated pincer-type femoroacetabular impingement using three
      dimensional CT.
AB  - PURPOSE: The objective of this study is to determine the clinical characteristics
      of residual bony impingement lesions after arthroscopic treatment for pincer-type
      femoroacetabular impingement (FAI); and to determine the effects of residual bony
      impingement lesions on the clinical outcomes after 2 years of follow-up. METHODS:
      From December 2010 to January 2012, 42 patients underwent arthroscopic surgery
      for symptomatic pincer-type FAI. Clinical outcomes were evaluated using the
      modified Harris Hip Score (mHHS) and satisfaction scores. To quantitatively
      evaluate the acetabular bony impingement lesions, the acetabular bony impingement
      angles were measured on three-dimensional CT scans. The incidence and residual
      rates of residual bony impingement were calculated. According to residual rates,
      the patients were divided into three groups: group 1, residual rate <10 %; group
      2, residual rate 10-20 %; and group 3, residual rate >20 %. RESULTS: Thirty
      patients met the inclusion criteria and were enrolled in this study. The mean age
      was 34.5 years. The mean follow-up was 26.3 months. Nineteen cases had residual
      bony impingement lesions after surgery. The incidence was 63.3 % (19/30). Sixteen
      cases (84.2 %) had residual bony impingement lesions posterior to the actual
      acetabular resection zones. The preoperative and postoperative bony impingement
      angles were 77.47 degrees  +/- 21.31 degrees  and 12.94 degrees  +/- 18.04
      degrees , respectively. The residual rate was 14.48 %. The overall mHHS
      significantly improved (P < 0.001) from 55.18 +/- 7.96 preoperatively to 94.71 +/
      4.39 postoperatively. The overall satisfaction rate was 76.66 %. The
      postoperative mHHSs of groups 1-3 were 95.86 +/- 1.71, 95.23 +/- 1.99, and 85.52
      +/- 6.41, respectively. Group 3 exhibited significantly lower postoperative mHHS
      compared to the other two groups (P = 0.001). The satisfaction rates in groups 1
      3 were 92.86, 80, and 33.33 %, respectively. The satisfaction rate in group 3 was
      significantly worse than those of the other two groups (P = 0.017). There was a
      significant inverse linear relationship between the residual rate of bony
      impingement lesions and the postoperative mHHS (R (2) = 0.516, P < 0.05).
      CONCLUSION: The incidence of residual impingement lesions after arthroscopic
      pincer-type FAI correction was 63.3 %. The residual rate was 14.48 %. The
      residual impingement lesions were primarily in the posterior portion of the
      acetabulum. The clinical outcomes were associated with the residual rate of bony
      impingement lesions. The patients with residual rates >20 % exhibited
      significantly lower clinical scores and satisfaction rates.

PMID- 25990375
TI  - The Predictive Validity of the Return-to-Work Self-Efficacy Scale for Return-to
      Work Outcomes in Claimants with Musculoskeletal Disorders.
AB  - PURPOSE: To examine the predictive validity of the Return-to-Work Self-Efficacy
      (RTWSE) Scale in terms of the scale's baseline absolute values and of changes in
      self-efficacy scores, with the outcome of return-to-work (RTW) status in a sample
      of injured workers with upper extremity and back musculoskeletal disorders.
      METHODS: RTWSE was measured with a 10-item scale assessing Overall RTWSE and
      three self-efficacy subdomains: (1) ability to cope with pain, (2) ability to
      obtain help from supervisor and (3) ability to obtain help from co-workers.
      Outcome measures included RTW status (yes/no) measured at 6- and 12-month follow
      up. RTWSE improvement was defined as an increase in self-efficacy scores between
      baseline and 6-month follow-up time points. Logistic regression analyses were
      performed with RTW status as the dependent variable and adjusted for age, gender,
      educational level, personal income, pain site, pain severity, functional status,
      and depressive symptoms, and for baseline RTWSE scores in the improvement score
      analyses. RESULTS: A total of 632 claimants completed the baseline telephone
      interview 1 month post-injury; 446 subjects completed the 6-month interview (71
      %) and 383 subjects completed the 12-month interview (61 %). The baseline Pain
      RTWSE scores were found to be useful to predict RTW status 6 months post-injury,
      with a trend for baseline Overall RTWSE. Improvements over time in Overall RTWSE
      and in Co-worker RTWSE were found to be useful to predict 12-month RTW status,
      with trends for improvements in Supervisor RTWSE and Pain RTWSE. CONCLUSION: The
      study found evidence supporting the predictive validity of the RTWSE scale within
      12 months after injury. The RTWSE scale may be a potentially valuable scale in
      research and in managing work disabled claimants with musculoskeletal disorders.

PMID- 25990377
TI  - Biofilm architecture in a novel pressurized biofilm reactor.
AB  - A novel pure-oxygen pressurized biofilm reactor was operated at different organic
      loading, mechanical shear and hydrodynamic conditions to understand the
      relationships between biofilm architecture and its operation. The ultimate goal
      was to improve the performance of the biofilm reactor. The biofilm was labeled
      with seven stains and observed with confocal laser scanning microscopy. Unusual
      biofilm architecture of a ribbon embedded between two surfaces with very few
      points of attachment was observed. As organic loading increased, the biofilm
      morphology changed from a moderately rough layer into a locally smoother biomass
      with significant bulging protuberances, although the chemical oxygen demand (COD)
      removal efficiency remained unchanged at about 75%. At higher organic loadings,
      biofilms contained a larger fraction of active cells distributed uniformly within
      a proteinaceous matrix with decreasing polysaccharide content. Higher
      hydrodynamic shear in combination with high organic loading resulted in the
      collapse of biofilm structure and a substantial decrease in reactor performance
      (a COD removal of 16%). Moreover, the important role of proteins for the spatial
      distribution of active cells was demonstrated quantitatively. 

PMID- 25990378
TI  - Female Sexual Function Before and After Bariatric Surgery: a Cross-Sectional
      Study and Review of Literature.
AB  - BACKGROUND: The aims of the present study were to compare sexual quality of life
      and prevalence of female sexual dysfunction (FSD) after surgical weight loss with
      controls seeking bariatric surgery, and to perform a literature review. METHODS:
      Female Sexual Function Index (FSFI) and Sexual Quality of Life-Female (SQoL-F)
      questionnaires were sent within 12-18 months postoperatively via e-mail to 153
      women who had undergone weight loss surgery (postoperative group). The control
      group comprised of 23 women who were asked to complete the questionnaires during
      their preoperative evaluation (preoperative group). The total FSFI cutoff score
      for a diagnosis of FSD was <= 26.55. RESULTS: The median (Q1, Q3) FSFI score did
      not differ significantly between the preoperative (26.9 [24.3, 30.7]) and
      postoperative groups (26.9 [22.6, 30.0]). There was no difference in the
      prevalence of FSD between groups. However, median scores in FSFI domains of
      desire and arousal were significantly higher in the postoperative group. There
      were no differences in the other FSFI domains. The median SQoL-F was
      significantly higher in the postoperative group. CONCLUSIONS: The FSFI score did
      not predict the SQoL-F score. The prevalence of FSD was comparable in the two
      groups. The higher SQoL-F score in the postoperative group may be the result of
      an improvement in self-esteem, which in turn leads to greater interest in sex and
      more intense feelings of desire and arousal.

PMID- 25990379
TI  - The Effect of Weight Loss on Indigenous Australians with Diabetes: a study of
      Feasibility, Acceptability and Effectiveness of Laparoscopic Adjustable Gastric
      Banding.
AB  - BACKGROUND/OBJECTIVES: Diabetes and obesity are common and serious health
      challenges for indigenous people worldwide. The feasibility of achieving
      substantial weight loss, leading to remission of diabetes, was evaluated in a
      regional indigenous Australian community. SUBJECTS/METHODS: A prospective cohort
      study of 30 obese indigenous adults from the Rumbalara Aboriginal Co-operative in
      Central Victoria was performed. Inclusion criteria included aboriginality, BMI >
      30 kg/m(2) and diabetes diagnosed within the last 10 years. Weight loss was
      achieved using laparoscopic adjustable gastric banding (LAGB). Participants were
      treated in their community and followed for 2 years. Outcomes were compared with
      those of non-indigenous Australians from an earlier randomized controlled trial
      (RCT) using a similar protocol. RESULTS: 30 participants (26 females, mean age
      44.6 years; mean BMI 44.3) had LAGB at the regional hospital. Twenty-six
      participants completed diabetes assessment at 2 years follow-up. They showed
      diabetes remission (fasting blood glucose < 7.0 mmol/L and haemoglobin A1c
      (HbA1c) < 6.2 % while off all therapy except metformin) in 20 of the 26 and a
      mean weight loss (SD) of 26.0 (14) kilograms. Based on intention-to-treat,
      remission rate was 66 %. Quality of life improved. There was one early event and
      12 late adverse events. The outcomes for weight loss and diabetes remission were
      not different from the LAGB group of the RCT. CONCLUSIONS: For obese indigenous
      people with diabetes, a regionalized model of care centred on the LAGB is an
      effective approach to a serious health problem. The model proved feasible and
      acceptable to the indigenous people. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry (ACTRN 12609000319279).

PMID- 25990380
TI  - The Effect of Laparoscopic Sleeve Gastrectomy with Concomitant Hiatal Hernia
      Repair on Gastroesophageal Reflux Disease in the Morbidly Obese.
AB  - BACKGROUND: The effect of laparoscopic sleeve gastrectomy (LSG) on
      gastroesophageal reflux disease (GERD) is controversial. Although concomitant
      hiatal hernia repair (HHR) at the time of LSG is common and advocated by many,
      there are few data on the outcomes of GERD symptoms in these patients. The aim of
      this study was to evaluate the effect of concomitant HHR on GERD symptoms in
      morbidly obese patients undergoing LSG. METHODS: A single institution, multi
      surgeon, prospectively maintained database was examined to identify patients who
      underwent LSG and concomitant HHR from December 2010 to October 2013. Patient
      characteristics, operative details, and postoperative outcomes were analyzed.
      Standardized patient questionnaires administered both pre- and postoperatively
      were utilized. Primary endpoints included subjective reflux symptoms and the need
      for antisecretory therapy. Weight loss was considered a secondary endpoint.
      RESULTS: Fifty-eight patients were identified meeting inclusion criteria (LSG +
      HHR), with a mean follow-up of 97.5 weeks (range 44-172 weeks). The mean age of
      the cohort was 49.5 +/- 11.2 years, with 74.1 % being female. Mean preoperative
      BMI was 44.2 +/- 6.6 kg/m(2). Preoperative upper gastrointestinal contrast series
      was performed in all patients and demonstrated a hiatal hernia in 34.5 % of
      patients and reflux in 15.5 % of patients. Preoperatively, 44.8 % (n = 26) of
      patients reported subjective symptoms of reflux and/or required daily
      antisecretory therapy [Corrected]. After LSG + HHR, 34.6 % of symptomatic
      patients had resolution of their symptoms off therapy while the rest remained
      symptomatic and required daily antisecretory therapy; 84.4 % of patients that
      were asymptomatic preoperatively remained asymptomatic after surgery. New onset
      reflux symptoms requiring daily antisecretory therapy was seen in 15.6 % of
      patients who were previously asymptomatic. Post surgical weight loss did not
      correlate with the presence or resolution of reflux symptoms. CONCLUSION: Based
      on our data, LSG with concomitant HHR improved GERD symptoms or the need for
      daily antisecretory therapy only in a third of symptomatic patients. Furthermore,
      15.6 % of asymptomatic patients developed de novo GERD symptoms despite a HHR. In
      patients with a documented hiatal hernia, HHR does not lead to GERD resolution or
      prevention after LSG, indicating the need for appropriate patient counseling and
      further study.

PMID- 25990381
TI  - Cardiopexy with Ligamentum Teres in Patients with Hiatal Hernia and Previous
      Sleeve Gastrectomy: An Alternative Treatment for Gastroesophageal Reflux Disease.
AB  - BACKGROUND: Fifty percent of patients who have undergone sleeve gastrectomy have
      gastroesophageal reflux disease (GERD). Surgical reinforcement of the lower
      esophageal sphincter is necessary to prevent acid reflux. Here, we describe
      ligamentum teres cardiopexy, a surgical technique that reinforces the lower
      esophageal sphincter and restores its competence with a new valve, in patients
      with previous sleeve gastrectomy and hiatal hernia. METHODS: Included in the
      study were 15 patients (age, 35.6 +/- 15.2 years; 13 females [86.6 %]; mean pre
      cardiopexy body mass index, 21.94 kg/m(2)) with sleeve gastrectomy who presented
      with hiatal hernia and gastroesophageal reflux disease and underwent ligamentum
      teres cardiopexy. In this procedure, the ligamentum teres is released from its
      umbilical connection and the hernia reduced by manual traction, freeing the last
      3-5 cm of esophagus in the abdomen. The distal ligamentum teres is fixed with one
      stitch to the apex of the angle of His, one at the gastroesophageal junction, and
      one joining the gastric fundus to the esophagus. The remainder of the ligamentum
      teres is fixed over itself with four to six stitches, forming a necktie
      cardiopexy. The procedure concludes with diaphragmatic crus closure. RESULTS:
      After 6 months, 13 patients (86.6 %) achieved successful results, defined as
      resolution of GERD, no proton-pump inhibitor (PPI) use, and manometry measurement
      over 12 mmHg after surgery. Two patients (13.3 %) required continued proton-pump
      inhibition. CONCLUSIONS: Ligamentum teres cardiopexy combined with closure of the
      gastric crus is a good alternative treatment for gastroesophageal reflux disease
      in patients with previous sleeve gastrectomy and hiatal hernia.

PMID- 25990382
TI  - The Impact of Gender Stereotypes on Legal Perceptions of Lesbian Intimate Partner
      Violence.
AB  - The present study examined legal perceptions of lesbian intimate partner violence
      (IPV) in an experimental context. Undergraduate women and men from the
      Southeastern United States ( N = 217) read a trial summary in which the defendant
      was charged with physically assaulting her same-sex partner. The trial varied as
      to whether the victim and defendant were depicted via images as either feminine
      or masculine. Participants rendered verdicts and made judgments about the victim
      and defendant (e.g., credibility). Results indicated that the victim's and
      defendant's masculine or feminine appearance affected these judgments. Female
      participants viewed a masculine victim as more credible than a feminine victim
      when the defendant was masculine. When the victim was masculine, they viewed a
      masculine defendant as more responsible for the victim's injuries than a feminine
      defendant. Male participants had higher sympathy for a masculine versus feminine
      victim overall, but had more anger toward a masculine defendant versus a feminine
      defendant accused of assaulting a feminine victim. Finally, fewer participants
      mentioned the defendant's history of violence as a reason for a guilty of felony
      verdict for a feminine victim with a feminine defendant versus all other
      combinations of victim and defendant masculine/feminine appearance. Results are
      discussed in terms of gender stereotypes influencing legal decision-making in IPV
      cases among lesbian couples.

PMID- 25990383
TI  - Exploring University Students' Coping Strategy Intentions for Cyberbullying.
AB  - Most of the published research on cyberbullying has been conducted with children
      and adolescents, so little is known about cyberbullying in other populations.
      This study examined cyberbullying within an emerging adult population in a
      university setting ( N = 282), and explored what coping strategies these
      individuals intended to use in response to future cyberbullying incidents.
      Blocking of the sender of the bullying message was found to be the most frequent
      intention to cope with cyberbullying among these emerging adults. It was also
      found that both gender and victimisation status (i.e., whether the emerging adult
      had, in the preceding twelve months, been a victim of cyberbullying) influenced
      coping strategy intentions. The implications for practice and future research are
      discussed.

PMID- 25990384
TI  - Post-Traumatic Stress Symptoms in Police Officers Following Violent Assaults: A
      Study on General and Police-Specific Risk and Protective Factors.
AB  - Based on a study of 681 German police officers who were violently assaulted we
      analyze first general pre-, peri- and post-traumatic risk factors (e.g. trauma
      severity, psychological adjustment, social support) of post-traumatic stress
      symptoms, second police-specific factors (e.g. colleague support) and third
      differences in the impact of these factors comparing male and female officers.
      Using regression analysis we show that risk factors that were found to be
      important for the general population partly hold for the special group of
      victimized police officers. Regarding police-specific factors regular preparatory
      and follow-up sessions reduce post-traumatic stress symptoms, while facing legal
      action following the assault increases it. The findings also reveal that three
      factors are significantly more strongly correlated with post-traumatic stress
      symptoms for female compared to male officers.

PMID- 25990385
TI  - Homelessness and housing crises among individuals accessing services within a
      Canadian emergency department.
AB  - ACCESSIBLE SUMMARY: Studies have indicated that individuals who are homeless
      access hospital emergency departments more frequently and may have different
      needs than individuals who are housed. Successful interventions have been
      developed and tested to reduce discharge to homelessness for psychiatric
      inpatients but have not been similarly tested for discharge from emergency
      departments. This study was developed to provide baseline data on this issue to
      inform future emergency department interventions. Findings from the current study
      suggest that discharge from emergency departments to homelessness happens
      frequently in London, Canada. Participants are unlikely to spontaneously disclose
      their housing/homelessness issue when first entering the emergency department,
      which may result in services that do not adequately meet their complex needs.
      Screening for housing issues is necessary within emergency departments and
      psychiatric crisis teams as housing issues may be a reason for accessing care or
      contribute to the presenting condition. Nurses are in an ideal position to
      evaluate housing needs among emergency department patients. Services outside of
      the emergency department are also needed to address housing issues, particularly
      outside of regular office hours. ABSTRACT: Individuals who have mental health
      issues and are homeless or in housing crisis have been found to access emergency
      departments more frequently than individuals with stable housing. While emergency
      departments primarily focus on medical issues, homeless individuals may require
      psychosocial support as well. This study examined issues around housing crises
      and emergency department use for individuals with mental illness in Canada.
      Collecting baseline data about these issues is important to inform subsequent
      interventions. Administrative data from a hospital emergency department and
      psychiatric crisis service were collected, and five individuals accessing the
      emergency department for psychiatric reasons were interviewed. Results indicated
      that individuals with an identified housing crisis accessed the emergency
      department 930 times in 6 months. None of the interview participants identified
      housing as the primary reason for accessing the emergency department, but all
      noted that housing was a contributing stressor. Future research is needed to
      examine ways in which discharge to homelessness from emergency departments can be
      avoided and identify alternative services to address housing concerns,
      particularly for individuals with mental illness. Crisis service and emergency
      department staff, especially nurses, can play an important role in screening for
      housing issues and connecting individuals to outside services.

PMID- 25990386
TI  - OsTCTP, encoding a translationally controlled tumor protein, plays an important
      role in mercury tolerance in rice.
AB  - BACKGROUND: Mercury (Hg) is not only a threat to public health but also a growth
      risk factor to plants, as it is readily accumulated by higher plants.
      Accumulation of Hg in plants disrupts many cellular-level functions and inhibits
      growth and development; however, the detoxification and tolerance mechanisms of
      plants to Hg stress are still not fully understood. Exposure to toxic Hg also
      occurs in some crops cultivated under anoxic conditions, such as rice (Oryza
      sativa L.), a model organism and one of the most important cultivated plants
      worldwide. In this study, we functionally characterized a rice translationally
      controlled tumor protein gene (Os11g43900, OsTCTP) involved in Hg stress
      tolerance. RESULTS: OsTCTP was ubiquitously expressed in all examined plant
      tissues, especially in actively dividing and differentiating tissues, such as
      roots and nodes. OsTCTP was found to localize both the cytosol and the nucleus.
      OsTCTP was induced by mercuric chloride, cupric sulfate, abscisic acid, and
      hydrogen peroxide at the protein level in a time-dependent manner. Overexpression
      of OsTCTP potentiated the activities of several antioxidant enzymes, reduced the
      Hg-induced H2O2 levels, and promoted Hg tolerance in rice, whereas knockdown of
      OsTCTP produced opposite effects. And overexpression of OsTCTP did not prevent Hg
      absorption and accumulation in rice. We also demonstrated that Asn 48 and Asn 97
      of OsTCTP amino acids were not the potential N-glycosylation sites. CONCLUSIONS:
      Our results suggest that OsTCTP is capable of decreasing the Hg-induced reactive
      oxygen species (ROS), therefore, reducing the damage of ROS and enhancing the
      tolerance of rice plants to Hg stress. Thus, OsTCTP is a valuable gene for
      genetic engineering to improve rice performance under Hg contaminated paddy
      soils.

PMID- 25990387
TI  - Oral mucosal disease in an Australian urban Indigenous community using
      autofluorescence imaging and reflectance spectroscopy.
AB  - BACKGROUND: The aim of this study was to document the oral mucosal burden in an
      urban Indigenous community and to evaluate the efficacy of an adjunctive optical
      device (Identafi(TM) ) in a general dental practice. METHODS: Three hundred and
      forty-two patients who presented to an urban Aboriginal and Torres Strait
      Islander Community Health Service (ATSICHS) were examined using conventional oral
      examination (COE) and with a multispectral device (Identafi(TM) ). Loss of
      autofluorescence (LAF) and the visibility of diffuse vasculature were noted.
      RESULTS: The urban Indigenous community assessed did not display significantly
      higher rates of smoking, alcohol consumption or lesion prevalence compared to non
      Indigenous counterparts. The white and violet light functions of Identafi(TM)
      provided excellent lesion visibility in 84.5% and 77.9% of cases respectively
      compared to 75% with COE, and were capable of highlighting new lesions not seen
      during COE. CONCLUSIONS: The urban Indigenous community does not appear to
      display a significantly higher prevalence of risk factors such as smoking and
      alcohol consumption compared to their non-Indigenous counterparts living in the
      same region, nor are they more likely to have oral mucosal lesions. The incidence
      of intraoral pigmentation has the potential to complicate use of autofluorescence
      screening devices, emphasizing the importance of skill and training when using
      this technology.

PMID- 25990389
TI  - Synthesis of porous carbon fibers with strong anion exchange functional groups.
AB  - Hybrid porous carbon fibers with strong anion-exchangeable functional groups
      (HACAX) were synthesized by alkylation of pyrolyzed polyacrylonitrile. HACAX
      exhibits generic stable positively charged functional groups. This expands the
      applications of porous carbon media for interacting with anions without adjusting
      pH, such as Cr(vi) adsorption at natural pH. 

PMID- 25990388
TI  - Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for
      Diagnosis, Response Prediction, and Monitoring of Targeted Therapy.
AB  - Biomarkers of inflammatory bowel disease (IBD) are non-invasive or minimally
      invasive tests for IBD diagnosis and/or prognosis as well as assessment of
      disease activity and response to therapy. Here, we update the current status of
      IBD biomarkers, including serological, fecal, and genetic (DNA and microRNA
      [miRNA]) biomarkers. As an update, the classical serological biomarkers,
      including ASCA, pANCA, anti-OmpC, anti-Cbir, anti-I2, and other anti-glycan
      antibodies, are discussed only briefly. Emphasis in this article is given to
      those that have been recently identified or extensively characterized, as well as
      to the clinical utilities of biomarkers, with special attention to prediction of
      disease complication and activity assessment, mucosal healing, and response to
      therapies. In particular, we discuss the utilities of blood-based biomarkers
      predicting therapeutic response to anti-tumor necrosis factor (TNF)-alpha, such
      as anti-anti-TNFalpha antibodies or anti-drug antibodies (ADA) and trough level
      of anti-TNFalpha. Fecal biomarkers, which have recently attracted substantial
      attention, are also discussed extensively, including the well-characterized
      calprotectin and lactoferrin, as well as the recently characterized M2-PK,
      CHI3L1, neopterin, MMP-9, and HMGB1. Genome and exome sequencing enables the
      discovery of a number of rare yet disease-defining IBD-susceptible genes,
      particularly those involved in very early onset IBD, providing rare yet extremely
      useful biomarkers at genetic levels for IBD diagnosis/prognosis. Finally, we
      briefly summarize the discovery, characterization, and potential implications of
      miRNA as potential IBD biomarkers. 

PMID- 25990390
TI  - The expression of CXCL13 and its relation to unfavorable clinical characteristics
      in young breast cancer.
AB  - BACKGROUND: Young breast cancer occupies a higher and higher proportion of breast
      cancer, especially in Asia, and is associated with a more unfavorable prognosis
      compared with the disease arising in older women. However, the poor prognosis of
      young breast cancer cannot be fully explained by the clinical and molecular
      factors. METHODS: This study investigated 1125 Chinese breast cancer patients
      diagnosed from 2009 to 2013. A data mining of gene expression profiles was
      performed for the young and older breast cancer patients, identifying
      significantly differentially expressed genes. Quantitative RT-PCR, Western
      blotting and immunohistochemistry assay were carried out for the clinical sample
      validations. RESULTS: The investigation firstly displayed that young patients
      (<=45 years) accounted for 47.6 % (535/1125) of breast cancer, and clinically
      associated with some unfavorable factors related to poor prognosis, such as
      invasive pathological type, high tumor grade, lymph node positive, ER negative
      and triple-negative subtype. Subsequently, 553 significantly differentially
      expressed genes were identified by the data mining. Of them, a set of genes
      related to immune function were observed to be up-regulated in young patients
      with breast cancer. Impressively, the CXCL13 (C-X-C motif chemokine 13)
      expression level showed the most significant difference (FC = 2.64, P = 8.2 * 10(
      4)). Furthermore, the validations with clinical samples and correlation analysis
      demonstrated that CXCL13 was indeed highly expressed in young breast cancer and
      closely associated with some prognostic factors including lymph node positive and
      ER negative. CONCLUSION: This is the first to indicate the clinical relevance of
      CXCL13 to young breast cancer and represents a potential therapeutic target for
      young breast cancer.

PMID- 25990409
TI  - Identification of chemical constituents and rat metabolites of Kangxianling
      granule by HPLC-Q-TOF-MS/MS.
AB  - A high-performance liquid chromatography coupled with quadrupole time-of-flight
      mass tandem mass spectrometry method was established to characterize the chemical
      constituents of Kangxianling granule (KXL), a traditional Chinese medicine
      formula, and the metabolic profile in rat urine and plasma after oral
      administration of KXL. A total of 27 compounds in KXL extract and 13 prototype
      compounds with 12 metabolites in rat urine and plasma were identified. Among the
      27 detected compounds, 15 were identified by comparing the retention time and MS
      data with that of reference compounds and the other 12 compounds were tentatively
      assigned based on the MS data and reference literature. The main prototype
      components absorbed in rat were amygdalin, salvianolic acid B, tanshinones and
      anthraquinones. Hydroxylation, glucuronidation and sulfation were the principal
      metabolic pathways in rat. The results revealed that the 25 compounds identified
      in rat urine and plasma were the potential active ingredients of KXL, which
      provides helpful chemical information for further study of the pharmacology
      mechanism of KXL.

PMID- 25990411
TI  - Glutathione-S-Transferase Deletions and Non-arteritic Anterior Ischemic Optic
      Neuropathy.
AB  - In this study, we aimed at investigating the association between glutathione-S
      transferase (GSTM1 and GSTT1) deletion genotypes and susceptibility to non
      arteritic anterior ischemic optic neuropathy (NAION). We hope our findings may
      contribute to the understanding NAION pathogenesis and provide some clues for the
      prevention and treatment of optic diseases. The NAION group contains 113 subjects
      (33 males and 80 females, mean age 55.3 +/- 9.8). And 98 subjects were enrolled
      in the control group (32 males and 66 females, mean age 56.7 +/- 10.2). The
      individuals involved in the study were matched by gender and age to obtain two
      homogenous groups. GSTM1- and GSTT1- genotype and the combined genotype were
      investigated. The genotype distributions in NAION patients were compared with
      those in the controls. Significantly altered intraocular pressure (IOP) and cup
      to-disc ratio (CDR) was detected between NAION patients and controls. An
      increased risk of NAION was observed among individuals with GSTM1- (P < 0.001).
      No significant difference was confirmed for GSTT1- (P = 0.290). Individuals with
      GSTM1-/GSTT1- have a higher susceptibility to NAION (P < 0.001); the GSTM1
      /GSTT1+ genotype also had a significantly higher frequency in patients than in
      controls (P = 0.004). But the genotype of GSTM1+/GSTT1- seems to have no
      connection with NAION (P = 0.476). In conclusion, in this study, we confirmed the
      connection between NAION and GSTM1- genotype. But no significant association was
      observed between GSTT1- genotype and NAION susceptibility. In further analysis
      regarding combined genotype, a trend of protective effect was detected for GSTT1+
      genotype. It is indicated by our result that oxidative compounds might play an
      important part in the pathogenesis of NAION.

PMID- 25990410
TI  - Baseline diabetes as a way to predict CV outcomes in a lipid-modifying trial: a
      meta-analysis of 330,376 patients from 47 landmark studies.
AB  - BACKGROUND: Diabetes is a major cardiovascular risk factor. However, its
      influence on the rate of occurrence of cardiovascular (CV) events during a
      clinical trial that included a diabetes subgroup has not yet been quantified.
      AIMS: To establish equations relating baseline diabetes prevalence and incident
      CV events, based on comparator arms data of major lipid-modifying trials.
      METHODS: Meta-analysis of primary outcomes (PO) rates of key prospective trials,
      for which the baseline proportion of diabetics was reported, including studies
      having specifically reported CV outcomes within their diabetic subgroups.
      RESULTS: 47 studies, representing 330,376 patients (among whom 124,115
      diabetics), were analyzed as regards the relationship between CV outcomes rates
      (including CHD) and the number of diabetics enrolled. Altogether, a total of
      18,445 and 16,156 events occurred in the comparator and treatment arms,
      respectively. There were significant linear relationships between diabetes
      prevalence and both PO and CHD rates (%/year): y = 0.0299*x + 3.12 [PO] (p =
      0.0128); and y = 0.0531*x + 1.54 [CHD] (p = 0.0094), baseline diabetes predicting
      PO rates between 3.12 %/year (no diabetic included) and 6.11 %/year (all patients
      diabetic); and CHD rates between 1.54 %/year (no diabetic) and 6.85 %/year (all
      patients diabetic). The slopes of the equations did not differ according to
      whether they were derived from primary or secondary prevention trials.
      CONCLUSIONS: Absolute and relative CV risk associated with diabetes at inclusion
      can be readily predicted using linear equations relating diabetes prevalence to
      primary outcomes or CHD rates.

PMID- 25990413
TI  - Automated quantitative cytological analysis using portable microfluidic
      microscopy.
AB  - In this article, a portable microfluidic microscopy based approach for automated
      cytological investigations is presented. Inexpensive optical and electronic
      components have been used to construct a simple microfluidic microscopy system.
      In contrast to the conventional slide-based methods, the presented method employs
      microfluidics to enable automated sample handling and image acquisition. The
      approach involves the use of simple in-suspension staining and automated image
      acquisition to enable quantitative cytological analysis of samples. The
      applicability of the presented approach to research in cellular biology is shown
      by performing an automated cell viability assessment on a given population of
      yeast cells. Further, the relevance of the presented approach to clinical
      diagnosis and prognosis has been demonstrated by performing detection and
      differential assessment of malaria infection in a given sample.

PMID- 25990412
TI  - Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related
      Hearing Loss in Pax2-Isl1 Transgenic Mice.
AB  - The development, maturation, and maintenance of the inner ear are governed by
      temporal and spatial expression cascades of transcription factors that form a
      gene regulatory network. ISLET1 (ISL1) may be one of the major players in this
      cascade, and in order to study its role in the regulation of inner ear
      development, we produced a transgenic mouse overexpressing Isl1 under the Pax2
      promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1(+)
      domain and induces accelerated nerve fiber extension and branching in E12.5
      embryos. Despite these gains in early development, the overexpression of ISL1
      impairs the maintenance and function of hair cells of the organ of Corti. Mutant
      mice exhibit hyperactivity, circling behavior, and progressive age-related
      decline in hearing functions, which is reflected in reduced otoacoustic emissions
      (DPOAEs) followed by elevated hearing thresholds. The reduction of the amplitude
      of DPOAEs in transgenic mice was first detected at 1 month of age. By 6-9 months
      of age, DPOAEs completely disappeared, suggesting a functional inefficiency of
      outer hair cells (OHCs). The timing of DPOAE reduction coincides with the onset
      of the deterioration of cochlear efferent terminals. In contrast to these effects
      on efferents, we only found a moderate loss of OHCs and spiral ganglion neurons.
      For the first time, our results show that the genetic alteration of the medial
      olivocochlear (MOC) efferent system induces an early onset of age-related hearing
      loss. Thus, the neurodegeneration of the MOC system could be a contributing
      factor to the pathology of age-related hearing loss.

PMID- 25990414
TI  - Low-dose combined oral contraceptive use is associated with lower bone mineral
      content variation in adolescents over a 1-year period.
AB  - BACKGROUND: Low-dose combined oral contraceptives (COCs) can interfere with bone
      mass acquisition during adolescence. This study aimed to evaluate bone mineral
      density (BMD) and bone mineral content (BMC) in female adolescents taking a
      standard low-dose COC (ethinylestradiol 20 MUg/desogestrel 150 MUg) over a 1-year
      period and to compare their data with those of healthy adolescents from the same
      age group not taking COCs. METHODS: This was a non-randomized parallel-control
      study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years,
      divided into COC users (n = 41) taking 20 MUg ethinylestradiol/150 MUg
      desogestrel and COC non-user controls (n = 26), were evaluated by bone
      densitometry examinations at baseline and after 12 months. Comparisons between
      the groups at the study onset were performed using the Mann-Whitney test with the
      significance level fixed at 5% or p < 0.05. Comparisons between the groups at the
      study onset and after 12 months were based on variations in the median
      percentages for bone mass variables. RESULTS: The COC users presented with low
      bone mass acquisition in the lumbar spine, and had BMD and BMC median variations
      of 2.07% and +1.57%, respectively, between the measurements at baseline and 12
      months. The control group had median variations of +12.16% and +16.84% for BMD
      and BMC, respectively, over the same period. The total body BMD and BMC showed
      similar evolutions during the study in both groups. Statistical significance (p <
      0.05) was seen for the BMC percentage variation between COC users and non-users.
      CONCLUSIONS: Use of a low-dose COC (ethinylestradiol 20 MUg/desogestrel 150 MUg)
      was associated with lower bone mass acquisition in adolescents during the study
      period. TRIAL REGISTRATION: Registry Number, RBR-5h9b3c.

PMID- 25990416
TI  - Rearing system and oleic acid supplementation effect on carcass and lipid
      characteristics of two muscles from an obese pig breed.
AB  - Quality of pork depends on genotype, rearing and pre- and post-slaughter
      conditions. However, no information is available on rearing system changes and
      oleic acid supplementation on carcass characteristics and fatty acid (FA) profile
      of pork from the Alentejano (AL) pig, an obese breed. This study evaluates the
      effects of feeding low (LO) or high oleic acid diets (HO) to AL pigs reared in
      individual pens (IND) or outdoor (OUT) with access to pasture. Carcass
      composition was obtained and longissimus dorsi and semimembranosus samples were
      collected to analyse chemical composition and neutral and polar intramuscular
      lipids FA profile by gas chromatography. Statistical analysis was performed by a
      two-way ANOVA for rearing system and diet effects. OUT-reared pigs presented
      leaner carcasses than IND-reared ones. Both muscles presented lower intramuscular
      lipid content in OUT-reared pigs. Treatments affected the FA profile of muscles.
      Overall, OUT-reared pigs presented lower n-6/n-3 FA ratios, whereas pigs fed the
      HO diet exhibited lower saturated fatty acids (SFA), higher monounsaturated fatty
      acids (MUFA) levels and lower thrombogenic indexes on neutral intramuscular
      lipids than LO-fed pigs. On the polar fraction, OUT-reared pigs presented lower
      SAT and n-6/n-3 FA ratio, and higher polyunsaturated fatty acids (PUFA) levels on
      both muscles. Pigs fed the HO diet exhibited higher MUFA and lower PUFA levels on
      both muscles, and lower SAT levels on semimembranosus. This study shows rearing
      system and oleic acid supplementation have complementary effects and influence
      carcass composition and the nutritional quality of meat. 

PMID- 25990415
TI  - Expression of eight glucocorticoid receptor isoforms in the human preterm
      placenta vary with fetal sex and birthweight.
AB  - INTRODUCTION: Administration of betamethasone to women at risk of preterm
      delivery is known to be associated with reduced fetal growth via alterations in
      placental function and possibly direct effects on the fetus. The placental
      glucocorticoid receptor (GR) is central to this response and recent evidence
      suggests there are numerous isoforms for GR in term placentae. In this study we
      have questioned whether GR isoform expression varies in preterm placentae in
      relation to betamethasone exposure, fetal sex and birthweight. METHODS: Preterm
      (24-36 completed weeks of gestation, n = 55) and term placentae (>37 completed
      weeks of gestation, n = 56) were collected at delivery. Placental GR expression
      was examined using Western Blot and analysed in relation to gestational age at
      delivery, fetal sex, birthweight and betamethasone exposure. Data was analysed
      using non-parametric tests. RESULTS: Eight known isoforms of the GR were detected
      in the preterm placenta and include GRalpha (94 kDa), GRbeta (91 kDa), GRalpha C
      (81 kDa) GR P (74 kDa) GR A (65 kDa), GRalpha D1-3 (50-55 kDa). Expression varied
      between preterm and term placentae with a greater expression of GRalpha C in
      preterm placentae relative to term placentae. The only sex differences in preterm
      placentae was that GRalpha D2 expression was higher in males than females. There
      were no alterations in preterm placental GR expression in association with
      betamethasone exposure. DISCUSSION: GRalpha C is the isoform involved in
      glucocorticoid induced apoptosis and suggests that its predominance in preterm
      placentae may contribute to the pathophysiology of preterm birth.

PMID- 25990417
TI  - Cost-effectiveness of liver transplantation in methylmalonic and propionic
      acidemias.
AB  - Propionic acidemia (PA) and classical methylmalonic acidemia (MMA) are rare
      inborn errors of metabolism that can cause early mortality and significant
      morbidity. The mainstay of disease management is lifelong protein restriction. As
      an alternative, liver transplantation (LT) may improve survival, quality of life,
      and prevent further neurological deterioration. The aim of our study was to
      estimate the incremental costs and outcomes of LT versus nutritional support in
      patients with early-onset MMA or PA. We constructed a Markov model to simulate
      and compare life expectancies, quality-adjusted life years (QALYs), and lifetime
      direct and indirect costs for a cohort of newborns with MMA or PA who could
      either receive LT or be maintained on conventional nutritional support. We
      conducted a series of 1-way and probabilistic sensitivity analyses. In the base
      case, LT on average resulted in 1.5 more life years lived, 7.9 more QALYs, and a
      savings of $582,369 for lifetime societal cost per individual compared to
      nutritional support. LT remained more effective and less costly in all 1-way
      sensitivity analyses. In the probabilistic sensitivity analysis, LT was cost
      effective at the $100,000/QALY threshold in more than 90% of the simulations and
      cost-saving in over half of the simulations. LT is likely a dominant treatment
      strategy compared to nutritional support in newborns with classical MMA or PA.

PMID- 25990419
TI  - Atherosclerosis: New insights into pathogenesis.

PMID- 25990420
TI  - Blood flow-induced remodeling of arteries in health and disease.
AB  - Vascular structures readily remodel in response to hemodynamic cues associated
      with changes in blood flows. These remodeling processes are invoked by a wealth
      of developmental, physiological, and pathological phenomena. Current work is
      providing novel clues concerning flow sensing by endothelial cells, the signal
      transduction pathways that translate flow detection into endothelial responses,
      and some of the signals that are transmitted to the effector cells, the vascular
      smooth muscle cells in the media. However, most of these mechanisms relate to
      acute responses to altered flow, and how important they are in eliciting tissue
      remodeling is unknown. Also, there is very little information on the processes
      that accomplish "modeling," beyond evidence that modulation of new tissue
      synthesis occurs. There is a potential for experiments in the near future to
      provide fundamental information on the genesis of the vascular structure-function
      relations, which now clearly spans much of the pre- and postnatal life. 

PMID- 25990421
TI  - The role of endothelial cells in vascular integrity and repair.

PMID- 25990418
TI  - A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk
      variants for colorectal cancer.
AB  - Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified
      23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate
      additional risk loci are yet to be discovered. To identify novel CRC
      susceptibility loci, we conducted a new GWAS and performed a meta-analysis with
      five published GWAS (totalling 7,577 cases and 9,979 controls of European
      ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined
      analysis identified new, significant associations with CRC at 1p36.2 marked by
      rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 *
      10(-8), odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21,
      P = 5.06 * 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11
      58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we
      identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF
      = 0.32, P = 7.01 * 10(-8); OR = 1.14). These findings provide further insights
      into the genetic and biological basis of inherited genetic susceptibility to CRC.
      Additionally, our analysis further demonstrates that imputation can be used to
      exploit GWAS data to identify novel disease-causing variants. 

PMID- 25990422
TI  - Cell proliferation in human arteries.
AB  - The development and progression of human atherosclerosis appears to be associated
      with low levels of cell proliferation and with proliferative activity seen in
      both smooth muscle cells and monocyte/macrophages. The time courses and patterns
      of cell proliferation in this disease are just beginning to be addressed. 

PMID- 25990423
TI  - Restenosis: Animal models and morphometric techniques in studies of the vascular
      response to injury.
AB  - Percutaneous transluminal coronary angioplasty has become a frequently used,
      clinically effective method for the revascularization of stenosed or occluded
      native arteries And vein grafts. However, the problem of restenosis, which occurs
      in 25% to 50% of patients who undergo intravascular intervention, continues to
      significantly affect the clinical utility of this procedure. It is apparent that
      many forms of vascular injury result in the cascade of events that lead to
      neointimal proliferation and restenosis. The pathogenesis of this restenosis
      process is not well understood. In vitro techniques and animal models are
      currently being used to elucidate some of the mechanisms of restenosis. The
      purpose of this discussion is to review the animal models currently used in
      vascular biology research and describe morphometric techniques that can be
      employed to evaluate these model systems. Proper model systems and accurate
      morphometric techniques are necessary to provide data that will answer the
      specific scientific questions that must be resolved in order to understand the
      pathogenesis of restenosis after vascular injury. 

PMID- 25990424
TI  - Pulmonary hypertension attributable to neoplastic emboli: An autopsy study of 20
      cases and a review of literature.
AB  - Twenty cases of pulmonary hypertension attributable to neoplastic emboli were the
      subject of this retrospective autopsy study (1951-1990) at the Mayo Clinic.
      Fourteen patients were women, and ages ranged from 18 to 82 years (mean 49). In
      three patients, tumor was clinically occult, and in only one case was the
      diagnosis of neoplastic pulmonary hypertension considered clinically. The mean
      interval between diagnosis of malignancy and development of respiratory symptoms
      was 14 months, but the mean interval between respiratory symptoms and death was
      only one month. At autopsy, the three most common primary sites for neoplasm were
      breast (40%), stomach (15%), and lung (10%). All 20 cases revealed subacute
      changes of pulmonary hypertension, either with medial hypertrophy of muscular
      pulmonary arteries (70%) or with right ventricular hypertrophy (45%) or
      dilatation (40%). However, three subgroups were identified based on microscopic
      and gross features: (i) 6 patients with predominantly neoplastic microemboli,
      (ii) 10 patients with mixed neoplastic and thrombotic microemboli, and (iii) 4
      cases with both neoplastic microemboli and large, fatal tumor emboli (primary
      tumors in kidney, femur, cervix, and thyroid). In conclusion, neoplastic
      pulmonary hypertension is most commonly associated with carcinoma of the breast,
      accounting for the observed female preponderance. It is generally associated with
      a rapid clinical course once respiratory symptoms develop, and large, fatal,
      acute neoplastic emboli account for a substantial number of deaths (20% in the
      present series). 

PMID- 25990425
TI  - Pulmonary veno-occlusive disease associated with hypertrophic cardiomyopathy.
AB  - An autopsy analysis of the lung findings in 14 cases of hypertrophic
      cardiomyopathy (HCM) was undertaken, with particular attention paid to the
      pulmonary vessels. Six of the 14 cases of HCM showed histological features of
      pulmonary veno-occlusive disease (PVOD). The coexistence of these two rare
      conditions appears to be more than a chance association. In view of recent
      advances in the understanding of the genetic basis for HCM, genetic analysis of
      patients with PVOD should be performed in order to determine whether there may be
      a common genetic context for the coexistence of these disorders. 

PMID- 25990426
TI  - The response to percutaneous transluminal coronary angioplasty: An
      ultrastructural study of smooth muscle cells and endothelial cells.
AB  - We investigated the ultrastructure of the repair tissue formed after percutaneous
      transluminal coronary angioplasty (PTCA). Four hearts (6 coronary arteries) were
      investigated; 5 arteries after single PTCA and 1 after repeated PTCA. In the
      earliest lesion (5 days after PTCA), all smooth muscle cells were of a synthetic
      phenotype, with abundant rough endoplasmic reticulum and few myofilaments,
      whereas the oldest lesion (259 days after PTCA) was composed of contractile
      smooth muscle cells, characterized by abundant myofilaments and small amounts of
      rough endoplasmic reticulum. In lesions taken at intermediate times (74 and 77
      days), the smooth muscle cells were of an intermediate phenotype, with rough
      endoplasmic reticulum and myofilaments present in approximately equal portions.
      Regenerating endothelial cells observed at 74 days after PTCA were characterized
      by a rounded shape and a paucity of intercellular connections in the form of
      simple junctions, which suggested an immature state. At 259 days after PTCA, the
      endothelial cells were more mature, as indicated by a flat shape and the presence
      of many tight junctions and a complete basement membrane. The findings suggest a
      relation between the stage of endothelial cell regeneration and the phenotype of
      the smooth muscle cells. 

PMID- 25990427
TI  - Microfibrillar cardiomyopathy: An infiltrative heart disease resembling but
      distinct from cardiac amyloidosis.
AB  - Microfibrils-small, ubiquitous components of the extracellular matrix in many
      tissues-generally have not been recognized as causing infiltrative heart disease,
      except in a group of cardiac transplant patients treated with cyclosporin.
      Microfibrils are often associated with elastic tissue and contain the
      glycoprotein fibrillin, the P component of amyloid, and bound fibronectin. A
      genetically determined abnormality of fibrillin caused by point mutations of
      fibrillin genes recently was reported as the cause of Marfan's syndrome. However,
      to date, no abnormalities of increased fibrillin tissue deposition have been
      observed. In the last two years, while examining right ventricular endomyocardial
      biopsies, in four patients we noted abnormal histology distinct from the usual
      type of congestive cardiomyopathy but with a strong resemblance to amyloidosis.
      The patients presented with unexplained ventricular tachycardia (N = 3) and/or
      congestive heart failure (N = 2). Biopsies revealed subendocardial, interstitial,
      and perivascular hyaline eosinophilic fibrillar material that did not stain with
      Congo red. Electron microscopy revealed that this material was organized into
      bundles of tangled microfibrils composed of twisted and tubular structures
      measuring up to 17 nm wide, which did not resemble amyloid or cyclosporin
      associated microfibrils. Immunoelectron microscopy of the index case, using
      monoclonal antibody to fibrillin, specifically identified these structures as
      fibrillin microfibrils; fibronectin also was bound to the interstitial
      microfibrils. We believe that the subendocardial and interstitial deposition of
      microfibrils in these four symptomatic patients may represent a new type of
      infiltrative cardiomyopathy, similar to but distinct from cardiac amyloidosis. We
      do not know yet if this disorder is genetic or acquired, or if the prognosis is
      better than that of cardiac amyloidosis. However, atypical cases of primary
      cardiac amyloidosis should be reevaluated in light of these findings. 

PMID- 25990428
TI  - Dilated cardiomyopathy in a zidovudine-treated AIDS patient.
AB  - The pathogenesis of dilated cardiomyopathy in acquired immunodeficiency syndrome
      (AIDS) is poorly understood. We report a case of an HIV-positive, 45-year-old
      homosexual male treated with high-dose azidothymidine (AZT, 1,200 mg/day) for two
      years prior to development of AIDS. He subsequently manifested symptoms of
      congestive heart failure with left ventricle dilation and a 20% ejection
      fraction. An endomyocardial biopsy showed no active myocarditis, but
      intramyocytic vacuoles were found. Transmission electron microscopy revealed
      mitochondrial cristae with distortion and myofibrillar loss. The clinical
      consideration was dilated cardiomyopathy in AIDS. His AIDS worsened and he died
      in October 1991. Autopsy revealed a 100-ml pericardial effusion, cardiomegaly,
      and biventricular dilation. Vacuolar changes in cardiac myocytes were present.
      Pathologic findings support a diagnosis of AZT-induced cardiotoxicity. Potential
      mechanisms are discussed. 

PMID- 25990430
TI  - How to optimize and use predictive models for postoperative pulmonary
      complications.
AB  - Pulmonary complications are a source of greater postoperative morbidity and
      mortality and longer hospital stays. Although many factors have been implicated
      as predictors, few models have been developed with the rigorous methodology
      required for clinically useful tools. In this article we attempt to describe what
      to look for when developing or assessing a newly proposed predictive tool and to
      discuss what must be taken into consideration on incorporating a model into
      clinical practice. Above all, we stress that we still lack evidence for the
      clinical and cost effectiveness of many measures proposed for reducing risk or
      for managing complications perioperatively. For a good predictive model to truly
      prove its utility in clinical decision-making, such evidence is required. 

PMID- 25990431
TI  - Bedside predictors of difficult intubation: a systematic review.
AB  - BACKGROUND: Unanticipated difficult intubation is associated with unwanted
      patient outcomes. The capability of predicting difficult airways may contribute
      to patient safety, efficient patient flow and rational use of limited resources.
      We evaluated current literature on performance of bedside airway tests in
      predicting difficult tracheal intubation. METHODS: Eligibility criteria were:
      prospective clinical studies; adult population of least 100 subjects; accepted
      definition of difficult intubation; direct laryngoscopy approach; true positive,
      false negative, false positive and true negative either reported or inferred.
      Medline and EMBASE database were searched for the following terms: "predictors",
      "prediction" and "risk factors" of "difficult intubation", "difficult
      laryngoscopy" and "difficult airway". The publication dates considered for the
      search were January 1st 2004 to March 31st 2014. Risk of bias was assessed
      according to QUADAS-2 criteria. RESULTS: Twenty-four studies involving 20,582
      patients and consistent with eligibility criteria were included. Numerous airways
      screening tests were evaluated. The most frequently performed tests were:
      Mallampati Score, measurement of thyro-mental distance, upper lip bite test,
      inter-incisors gap, and sterno-mental distance. Assessed individual and combined
      tests are characterized by limited discriminative capacity, sensitivity,
      specificity, and positive likelihood ratio. CONCLUSION: Current bedside tests
      have limited and inconsistent capacity to discriminate between patients with
      difficult and easy airways. Most studies are characterized by high risk of bias
      and concerns of applicability. Reliable bedside criteria to predict difficult
      intubation remain elusive.

PMID- 25990429
TI  - Cutaneous Leishmaniasis in dogs: is high seroprevalence indicative of a reservoir
      role?
AB  - American cutaneous leishmaniasis (ACL) is a complex disease with a rich diversity
      of animal host species. This diversity imposes a challenge, since understanding
      ACL transmission requires the adequate identification of reservoir hosts, those
      species able to be a source of additional infections. In this study we present
      results from an ACL cross-sectional serological survey of 51 dogs (Canis
      familiaris), where we used diagnostic tests that measure dog's exposure to
      Leishmania spp. parasites. We did our research in Panama, at a village that has
      undergone significant ecosystem level transformations. We found an ACL
      seroprevalence of 47% among dogs, and their exposure was positively associated
      with dog age and abundance of sand fly vectors in the houses of dog owners. Using
      mathematical models, which were fitted to data on the proportion of positive
      tests as function of dog age, we estimated a basic reproductive number (R 0 +/-
      s.e.) of 1.22 +/- 0.09 that indicates the disease is endemically established in
      the dogs. Nevertheless, this information by itself is insufficient to incriminate
      dogs as ACL reservoirs, given the inability to find parasites (or their DNA) in
      seropositive dogs and previously reported failures to experimentally infect
      vectors feeding on dogs with ACL parasites. 

PMID- 25990432
TI  - Hemostasis changes during veno-venous extracorporeal membrane oxygenation for
      respiratory support in adults.
AB  - BACKGROUND: We investigated the coagulation system in patients during
      extracorporeal membrane oxygenation (ECMO) initiated for respiratory failure and
      the influence of the ECMO circuit on coagulation tests; we compared different
      coagulation tests for monitoring unfractionated heparin (UH) therapy; we
      investigated whether or not coagulation parameters were predictive of bleeding
      during ECMO. METHODS: Pilot study on twelve consecutive adult patients admitted
      at our general ICU for acute respiratory failure and placed on ECMO from November
      2011 to October 2012. Coagulation tests were performed before ECMO start and
      daily, including day of circuit change and day of circuit removal. UH was
      monitored with activated partial thromboplastin time (APTT) ratio, at a
      therapeutic range of 1.5-2.0. RESULTS: We observed no effect of ECMO circuit on
      coagulation parameters measured pre- and postlung, but platelet count decreased
      significantly over time (-82x10(3)/mmc, 95%CI 40-123). APTT showed a correlation
      with antifactor Xa activity, whereas other global coagulation tests such as
      activated clotting time, thromboelastography and endogenous thrombin potential
      did not. Major bleeding occurred in three patients but no difference in any
      coagulation parameter was observed between them and those who did not bleed.
      CONCLUSIONS: This pilot study shows that ECMO initiated for respiratory support
      in adults does not change coagulation parameters. Over time a statistically
      significant reduction of platelet count was observed, possibly due to consumption
      within the circuit, consumption microangiopathy or the underlying patients'
      diseases. Although APTT was appropriate to monitor UH, major bleedings occurred
      and a lower therapeutic range may be advisable.

PMID- 25990433
TI  - Transpulmonary pressure cannot be determined without esophageal pressure in ARDS
      patients.

PMID- 25990434
TI  - Insights into Myeloid-Derived Suppressor Cells in Inflammatory Diseases.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells
      involved in immune regulation. This population subdivides into granulocytic MDSCs
      and monocytic MDSCs, which regulate immune responses via the production of
      various molecules including reactive oxygen species, nitric oxide, arginase-1,
      interleukin-10, and transforming growth factor-beta. Most studies of MDSCs
      focused on their role in tumors. MDSCs protect tumor cells from immune responses,
      and thus the frequency of MDSCs associates with poor prognosis. Many recent
      studies reported an important role for MDSCs in inflammatory diseases via the
      regulation of immune cells. In addition, the utilization of MDSCs by infectious
      pathogens suggests an immune evasion mechanism. Thus, MDSCs are important immune
      regulators in inflammatory diseases, as well as in tumors. This review focuses on
      the role of MDSCs in the regulation of inflammation in non-tumor settings. 

PMID- 25990435
TI  - Comparing the electronic relaxation dynamics of aniline and d(7)-aniline
      following excitation at 272-238 nm.
AB  - Femtosecond time-resolved photoelectron spectroscopy experiments have been used
      to compare the electronic relaxation dynamics of aniline and d7-aniline following
      photoexcitation in the range 272-238 nm. Together with the results of recent
      theoretical investigations of the potential energy landscape [M. Sala, O. M.
      Kirkby, S. Guerin and H. H. Fielding, Phys. Chem. Chem. Phys., 2014, 16, 3122],
      these experiments allow us to resolve a number of unanswered questions
      surrounding the nonradiative relaxation mechanism. We find that tunnelling does
      not play a role in the electronic relaxation dynamics, which is surprising given
      that tunnelling plays an important role in the electronic relaxation of
      isoelectronic phenol and in pyrrole. We confirm the existence of two time
      constants associated with dynamics on the 1(1)pisigma* surface that we attribute
      to relaxation through a conical intersection between the 1(1)pisigma* and
      1(1)pipi* states and motion on the 1(1)pisigma* surface. We also present what we
      believe is the first report of an experimental signature of a 3-state conical
      intersection involving the 2(1)pipi*, 1(1)pisigma* and 1(1)pipi* states. 

PMID- 25990436
TI  - Amino-terminal fragments of laminin gamma2 chain stimulate migration of
      metastatic breast cancer cells by interacting with CD44.
AB  - Laminin gamma2 (Lmgamma2) chain, a subunit of the basement membrane protein
      laminin-332, is regarded as a typical cancer invasion marker. The overexpression
      of Lmgamma2 chain by invasive cancer cells correlates with poor prognosis of
      cancer patients, and its forced expression in human cancer cells promotes their
      invasive growth in a nude mouse model. However, its actual roles in cancer
      progression, as well as the mechanism of its proinvasive effect, remain unclear.
      CD44 is known to be an important cancer stem cell marker and support cancer
      progression and stem cell functions. Here we demonstrate that amino-terminal
      fragments of Lmgamma2 interact with CD44 on the membrane of breast cancer cells.
      Lmgamma2 highly bound to the metastatic cell line MDA-MB-231 but poorly to the
      benign cell line MCF-7. The membrane receptor for Lmgamma2 on MDA-MB-231 cells
      was identified to be the standard form of CD44 (CD44s) by co-immunoprecipitation,
      affinity chromatography and direct protein interaction assay. Lmgamma2 interacted
      with CD44s through EGF-like repeat 2/3 in the Lmgamma2 amino-terminus. Amino
      terminal fragments of Lmgamma2 induced the phosphorylation of CD44 cytoplasmic
      domain and stimulated migration of the cancer cells in a CD44-dependent manner.
      This migration was blocked by inhibitors of TGF-beta receptor I (TGF-betaRI)
      kinase. These results suggest that two important tumor markers, Lmgamma2 and
      CD44, cooperate for cancer progression and possibly for cancer stem cell
      functions. TGF-betaRI may be involved in the Lmgamma2/CD44 interaction.

PMID- 25990437
TI  - Crystallization-Driven Self-Assembly of Rod-Coil-Rod Pseudopolyrotaxanes into
      Spherical Micelles, Nanorods, and Nanorings in Aqueous Solutions.
AB  - A novel rod-containing block copolymer is constructed by supramacromolecular self
      assembly of alpha-cyclodextrin and a triblock copolymer with methoxy polyethylene
      glycol as the flanking chains and the midterm block alternately connected by 2,2
      dimethylolbutyric acid and isophorone diisocyanate. The assembled rod-containing
      block copolymer shows an exciting phenomenon of concentration- and pH-dependent
      morphological switching of well-defined nanostructures. In the solutions at pH
      9.2, spherical micelles, rod-like micelles, and hydrogel are observed
      successively with an increase of the concentration. Notably, the rod-like
      micelles are composed of spherical segments due to the combination of the
      crystalline cores of the spherical micelles. In addition, 1D nanostructures with
      different curvatures from linear rod-like micelles (pH 9.2) to ring-shaped
      micelles (pH 7.5) can be obtained by controlling the pH values of the assembled
      systems. 

PMID- 25990439
TI  - Influence of renovascular hypertension on the distribution of vasoactive
      intestinal peptide in the stomach and heart of rats.
AB  - Arterial hypertension is associated with serious dysfunction of the
      cardiovascular system and digestive system. Given the relevant role of vasoactive
      intestinal peptide (VIP) in the regulation of digestion process, control of blood
      pressure and heart rate as well as cardio- and gastro-protective character of the
      peptide, it appeared worthwhile to undertake the research aimed at
      immunohistochemical identification and evaluation of VIP-positive structures in
      the pylorus and heart of hypertensive rats. Up to now, this issue has not been
      investigated. The experimental model of hypertension in rats according to
      Goldblatt (two-kidney one clip model of hypertension) was used in the study. The
      experimental material (pylorus and heart) was collected in the sixth week of the
      study. VIP-containing structures were evaluated using immunohistochemical and
      morphometric methods. The analysis of the results showed a significant increase
      in the number of immunoreactive VIP structures and in the intensity of
      immunohistochemical staining in the stomach and in the heart of hypertensive
      rats. Our findings indicate that VIP is an important regulator of cardiovascular
      and digestive system in physiological and pathological conditions. However, to
      better understand the exact role of VIP in hypertension further studies need to
      be carried out. 

PMID- 25990438
TI  - Fluorescent protein biosensors applied to microphysiological systems.
AB  - This mini-review discusses the evolution of fluorescence as a tool to study
      living cells and tissues in vitro and the present role of fluorescent protein
      biosensors (FPBs) in microphysiological systems (MPSs). FPBs allow the
      measurement of temporal and spatial dynamics of targeted cellular events involved
      in normal and perturbed cellular assay systems and MPSs in real time. FPBs
      evolved from fluorescent analog cytochemistry (FAC) that permitted the
      measurement of the dynamics of purified proteins covalently labeled with
      environmentally insensitive fluorescent dyes and then incorporated into living
      cells, as well as a large list of diffusible fluorescent probes engineered to
      measure environmental changes in living cells. In parallel, a wide range of
      fluorescence microscopy methods were developed to measure the chemical and
      molecular activities of the labeled cells, including ratio imaging, fluorescence
      lifetime, total internal reflection, 3D imaging, including super-resolution, as
      well as high-content screening. FPBs evolved from FAC by combining
      environmentally sensitive fluorescent dyes with proteins in order to monitor
      specific physiological events such as post-translational modifications,
      production of metabolites, changes in various ion concentrations, and the dynamic
      interaction of proteins with defined macromolecules in time and space within
      cells. Original FPBs involved the engineering of fluorescent dyes to sense
      specific activities when covalently attached to particular domains of the
      targeted protein. The subsequent development of fluorescent proteins (FPs), such
      as the green fluorescent protein, dramatically accelerated the adoption of
      studying living cells, since the genetic "labeling" of proteins became a
      relatively simple method that permitted the analysis of temporal-spatial dynamics
      of a wide range of proteins. Investigators subsequently engineered the
      fluorescence properties of the FPs for environmental sensitivity that, when
      combined with targeted proteins/peptides, created a new generation of FPBs.
      Examples of FPBs that are useful in MPS are presented, including the design,
      testing, and application in a liver MPS.

PMID- 25990441
TI  - A novel treatment tool to address soft tissue dysfunction.
AB  - These authors describe how they use thermoplastic materials to augment home
      exercise programs for clients with chronic and post-surgical soft tissue
      dysfunction. They discuss how after thorough education is provided, this
      alternative tool may be given for patient use. -Victoria Priganc, PhD, OTR, CHT,
      CLT, Practice Forum Editor. 

PMID- 25990440
TI  - The effect of physical training on the N-methyl-N-nitrosourea-induced mammary
      carcinogenesis of Sprague-Dawley rats.
AB  - The impact of physical activity on carcinogenesis has been demonstrated in many
      studies. Taking into account the discrepant results of physical exercise on the
      cell proliferation and apoptosis of breast cancer, we aimed to examine the impact
      of physical training on N-methyl-N-nitrosourea-(MNU)-induced mammary
      carcinogenesis. Fifty female rats were divided into four groups according to the
      intensity of physical activity they undertook. The number of developed tumors,
      tumor volume, and histopathological diagnoses were noted. Apoptosis and cell
      proliferation were studied by the number of TUNEL-positive and Ki-67-expressing
      cells. We demonstrated a statistically significant decrease in the tumor number
      between all trained groups and the control group. The results were most
      pronounced in the group with a moderate intensity of training. Moreover, we
      showed a decrease in tumor volume as training intensity increased, though the
      differences were not statistically significant. The mean number of TUNEL-positive
      cancer cells was significantly higher in the training groups than in the control
      group. These data suggest that physical training, especially of moderate
      intensity, may alleviate MNU-induced mammary carcinogenesis. The results could
      suggest that physical exercise-induced apoptosis may be a protective mechanism. 

PMID- 25990442
TI  - Forearm amputees' views of prosthesis use and sensory feedback.
AB  - STUDY DESIGN: Qualitative descriptive. INTRODUCTION: The lack of sensory feedback
      in today's hand prostheses has been in focus recently but the amputees'
      experiences need to be further investigated. PURPOSE: To explore forearm
      amputees' views of prosthesis use and sensory feedback. METHODS: Thirteen
      unilateral congenital or traumatic forearm amputees were interviewed. The
      transcribed text was subjected to content analysis. RESULTS: Prostheses both
      facilitate and limit occupational performance. Appearance is important for
      identity and blending into society. The feeling of agency regarding the
      prostheses is present but not that of body ownership. Future expectations
      concerned improved mobility, cosmetics, and sensory feedback. CONCLUSIONS: This
      study allows a deeper understanding of the complex relationship between a
      prosthetic device and the wearer. Today's prostheses allow the wearer to feel
      agency concerning the artificial limb but the lack of sensory feedback seems to
      be an important factor still blocking the achievement of body ownership of the
      prosthesis. LEVEL OF EVIDENCE: Not applicable.

PMID- 25990443
TI  - The use of occupation-based assessments and intervention in the hand therapy
      setting - A survey.
AB  - STUDY DESIGN: Descriptive survey. INTRODUCTION: This study specifically explored
      the use of occupation-based assessments and intervention in the hand therapy
      setting, but also more generally, current practice trends about all assessments
      being utilized in this setting, frequency of their use, and therapists'
      perceptions about them. METHODS: An online survey was distributed via email to
      members of the American Society of Hand Therapists (ASHT). The survey consisted
      of ten questions and was administered via Survey Monkey. RESULTS: Responses were
      received from 22% of those surveyed. A descriptive analysis was completed of the
      results and indicated that over half use occupation-based assessments on a daily
      basis; most are related to ADL function and used for the development of goals.
      The primary reason for not utilizing occupation-based assessments is time
      limitation. Seventy-nine percent believe these measures are important for the
      services provided in the hand therapy setting. CONCLUSION: Occupation-based
      assessments and intervention are not utilized as much as therapists would like in
      the hand therapy setting, primarily due to time constraints. While not formally
      assessed, the majority of those who responded indicated that they do address
      occupation in their assessments and interventions. LEVEL OF EVIDENCE: Not
      applicable.

PMID- 25990444
TI  - Why do we need new patient-reported outcomes?

PMID- 25990445
TI  - Reliability, validity, and responsiveness of a Canadian French adaptation of the
      Western Ontario Rotator Cuff (WORC) index.
AB  - STUDY DESIGN: Clinical measurement. PURPOSE: Several questionnaires assess
      symptoms and functional limitations following shoulder disorders, but few are
      available in French. The purposes were to translate and culturally adapt the
      Western Ontario Rotator Cuff (WORC) index into Canadian French and to evaluate
      its validity, reliability and responsiveness. METHODS: In accordance with
      standard procedure, the WORC original version was translated and cross-culturally
      adapted into Canadian French (WORC-CF). Then, 87 patients with rotator cuff (RC)
      disorders completed the WORC-CF on three occasions: baseline, two days later to
      evaluate reliability, and four weeks later to evaluate responsiveness. RESULTS:
      Cross-cultural adaptation was performed without problems with content or
      language. WORC-CF was found to be reliable (Intraclass Correlation Coefficient =
      0.96), valid (high correlation with Disability of the Arm, Shoulder and Hand
      [DASH]) and responsive (Standardized Response Mean = 1.54). CONCLUSION: WORC-CF
      can now be used to assess functional impairment in patients with RC disorders.
      LEVEL OF EVIDENCE: Not applicable.

PMID- 25990446
TI  - Dietary intakes among South Asian adults differ by length of residence in the
      USA.
AB  - OBJECTIVE: To examine whether nutrient and food intakes among South Asian adult
      immigrants differ by length of residence in the USA. DESIGN: Cross-sectional
      analysis to examine differences in nutrient and food intakes by length of
      residence in the USA. Dietary data were collected using an interviewer
      administered, culturally appropriate FFQ, while self-reported length of residence
      was assessed using a questionnaire and modelled as tertiles. SETTING: The
      Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.
      SUBJECTS: Eight hundred and seventy-four South Asians (mean age=55 (sd 9) years;
      47 % women; range of length of residence in the USA=2-58 years), part of the
      baseline examination of the MASALA study. RESULTS: Intakes of fat, including
      saturated and trans fats, dietary cholesterol and n-6 fatty acids, were directly
      associated with length of residence, while intakes of energy, carbohydrate,
      glycaemic index and load, protein, dietary fibre, folate and K were inversely
      associated with length of residence (P trend <0.05). A longer length of residence
      in the USA was also associated with higher intakes of alcoholic beverages, mixed
      dishes including pizza and pasta, fats and oils, and lower intakes of beans and
      lentils, breads, grains and flour products, milk and dairy products, rice,
      starchy vegetables and sugar, candy and jam (P for differences across groups
      <0.05). CONCLUSIONS: Length of residence in the USA influences diet and nutrient
      intakes among South Asian adult immigrants and should be considered when
      investigating and planning dietary interventions to mitigate chronic disease
      risk.

PMID- 25990448
TI  - Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and
      chemotherapy for colorectal cancer.
AB  - BACKGROUND: Comprehensive gene-expression analysis is very useful for classifying
      specific cancers into subgroups on the basis of their biological characteristics;
      it is used both prognostically and predictively. The purpose of this study was to
      classify unresectable advanced or recurrent colorectal cancer (CRC) by gene
      expression profiling of formalin-fixed paraffin-embedded tissues and to correlate
      CRC subgroups with clinicopathological and molecular features and clinical
      outcomes. METHODS: One hundred patients with advanced or recurrent CRC were
      enrolled. RNA extracted from FFPE tissues was subjected to gene-expression
      microarray analysis. RESULTS: The patients were stratified into four subgroups
      (subtypes A1, A2, B1, and B2) by unsupervised hierarchical clustering. By use of
      principle-components analysis (PCA), the patients were divided into subtypes A
      and B on the basis of component 1 and into subtypes 1 and 2 on the basis of
      component 2. Subtype A was significantly enriched among patients without the KRAS
      mutation and with an earlier clinical stage at diagnosis. With regard to anti
      EGFR therapy, progression-free survival (PFS) was better for patients in subtype
      A without the KRAS mutation than for those with the KRAS mutation (P = 0.047).
      PFS for patients without the KRAS mutation in subtype B was comparable with that
      for patients with the KRAS mutation (P = 0.55). Similar results were observed in
      a validation set. CONCLUSION: We found that gene-expression profiles enabled
      stratification of CRC patients into four subgroups. The efficacy of anti-EGFR
      therapy was correlated with component 1 from PCA. This comprehensive study may
      explain the heterogeneity of unresectable advanced or recurrent CRC and could be
      useful for identifying novel biomarkers for CRC treatment.

PMID- 25990449
TI  - Trends in the cervical cancer screening rates in a city in Japan between the
      years of 2004 and 2013.
AB  - BACKGROUND: The objective of our study was to evaluate trends in the cervical
      cancer screening rate in a city in Japan between the years of 2004 and 2013.
      METHODS: The cervical cancer screening rates for all female residents 20-49 years
      of age living in Toyonaka City for each year between 2004 and 2013 were analyzed
      and the effects of reminder letters and a free coupon program for cervical cancer
      screening on the subjects' behavior were evaluated. RESULTS: The screening rate
      increased on a single-year basis from 8.9 % (2004) to 12.7 % (2009) as a result
      of the free coupon program. From 2009 onward, the screening rate on a single-year
      basis remained stable. Although the free coupon program increased the rate of
      screening participation, it did not achieve a continuous increase in the number
      of subjects undergoing screening. Furthermore, despite recommendations for
      biennial screening, some subjects participated in consecutive screening within
      the last 2 years after receiving visits for a regularly scheduled residential
      screening program 1 year before/after the current screening program with a free
      coupon. There was a peak in the rate of screening participation at the end of the
      fiscal year among females eligible for the free coupon program. CONCLUSIONS:
      Excessive cervical cancer screening performed unnecessarily in the young is an
      unexpected limitation of free coupon programs. Further efforts to improve the
      screening rates are required, and the various factors leading young Japanese
      females to have a negative attitude toward cervical cancer screening should be
      identified.

PMID- 25990451
TI  - Response to 'What happens after R1 resection in patients undergoing laparoscopic
      total mesorectal excision for rectal cancer? A study in 333 consecutive patients'
      by Debove et al.

PMID- 25990450
TI  - Normal limits of the electrocardiogram in Indians.
AB  - AIMS: The objective of the study was to develop normal limits of the ECG in an
      apparently healthy population of South Asians living in India. METHODS: Three
      centres contributed to recording 12 lead ECGs on identical digital
      electrocardiographs. Apparently healthy volunteers were recruited and ECGs were
      first transferred to a local database and then to Glasgow where all ECGs were
      analysed by the same University of Glasgow ECG Interpretation Program. RESULTS: A
      total of 963 individuals were recruited into the study (30.4% female) with an age
      range of 18-83 years. QRS duration was longer in males than females, QT interval
      was longer in females than males, and QRS voltages in general were higher in
      males than females and in younger compared to older individuals. CONCLUSION:
      Findings in general paralleled those in other populations and suggested that
      criteria for a white Caucasian population could be applied to a South Asian
      Indian population.

PMID- 25990452
TI  - Dynamical origin of near- and below-threshold harmonic generation of Cs in an
      intense mid-infrared laser field.
AB  - Near- and below-threshold harmonic generation provides a potential approach to
      generate vacuum-ultraviolet frequency comb. However, the dynamical origin of in
      these lower harmonics is less understood and largely unexplored. Here we perform
      an ab initio quantum study of the near- and below-threshold harmonic generation
      of caesium (Cs) atoms in an intense 3,600-nm mid-infrared laser field. Combining
      with a synchrosqueezing transform of the quantum time-frequency spectrum and an
      extended semiclassical analysis, the roles of multiphoton and multiple
      rescattering trajectories on the near- and below-threshold harmonic generation
      processes are clarified. We find that the multiphoton-dominated trajectories only
      involve the electrons scattered off the higher part of the combined atom-field
      potential followed by the absorption of many photons in near- and below-threshold
      regime. Furthermore, only the near-resonant below-threshold harmonic is exclusive
      to exhibit phase locked features. Our results shed light on the dynamic origin of
      the near- and below-threshold harmonic generation. 

PMID- 25990453
TI  - Proteomics analysis of Listeria monocytogenes ATCC 19115 in response to
      simultaneous triple stresses.
AB  - Listeria monocytogenes can cause listeriosis in humans through consumption of
      contaminated food. L. monocytogenes can adapt and grow in a vast array of
      physiochemical stresses in the food production environment. In this study, we
      performed a proteomics strategy in order to investigate how L. monocytogenes
      survives with a simultaneous exposure to low pH, high salinity and low
      temperature. The results showed that the adaptation processes mainly affected the
      biochemical pathways related to protein synthesis, oxidative stress, cell wall
      and nucleotide metabolism. Interestingly, enzymes involved in the carbohydrate
      metabolism of energy, such as glycolysis and pentose phosphate pathway, were
      derepressed due to the down-regulation of CodY, a global transcriptional
      repressor. The down-regulation of CodY, together with the up-regulation of
      carbohydrate metabolism enzymes, likely leads to the accumulation of pyruvate and
      further to the activation of fatty acid synthesis pathway. Proteomics profiling
      offered a better understanding of the physiological responses of this pathogen to
      adapt to harsh environment and would hopefully contribute to improving the food
      processing and storage methods. 

PMID- 25990454
TI  - Inflammatory and metabolic responses to high-fat meals with and without dairy
      products in men.
AB  - Postprandial inflammation is an important factor for human health since chronic
      low-grade inflammation is associated with chronic diseases. Dairy products have a
      weak but significant anti-inflammatory effect on postprandial inflammation. The
      objective of the present study was to compare the effect of a high-fat dairy meal
      (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a
      high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and
      metabolic responses in healthy men. A cross-over study was conducted in nineteen
      male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after
      consumption of the test meals. Plasma concentrations of insulin, glucose, total
      cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP)
      were measured at each time point. IL-6, TNF-alpha and endotoxin concentrations
      were assessed at baseline and endpoint (6 h). Time-dependent curves of these
      metabolic parameters were plotted, and the net incremental AUC were found to be
      significantly higher for TAG and lower for CRP after consumption of the HFM meal
      compared with the HFD meal; however, the HFM and HFD meals were not different
      from the HFC meal. Alterations in IL-6, TNF-alpha and endotoxin concentrations
      were not significantly different between the test meals. The results suggest that
      full-fat milk and dairy products (cheese and butter) have no significant impact
      on the inflammatory response to a high-fat meal. 

PMID- 25990455
TI  - An antimicrobial peptide containing NGR motif has potent antitumor activity
      against CD13+ and CD13- tumor cells.
AB  - Antimicrobial peptides (AMPs) with Asn-Gly-Arg (NGR) motif have potent
      cytotoxicity, preferably against tumor cells due to their binding to CD13 on
      tumor cells. However, the importance of alphavbeta3 expression for antitumor
      activity of AMPs containing NGR has not been clarified. This study was aimed at
      designing a new AMP containing NGR and testing their biological activity against
      different types of tumor cells with varying CD13 and alphavbeta3 expression. We
      first synthesized the new AMP containing NGR motif (CK21), which effectively
      entered into CD13+ HT-1080, but less into CD13- alphavbeta3+ MDA-MB-435 and
      further less into stable alphavbeta3-silencing MDA-MB-435 cells. Furthermore,
      CK21 displayed dose-dependent antiproliferation against these tumor cells and
      induced cell cycling arrest at G2/M phases and apoptosis of these tumor cells. In
      addition, CK21 inhibited the invasion of these tumor cells in vitro and inhibited
      the growth of implanted tumor cells in vivo. Particularly, the antitumor effect
      of CK21 in CD13+ HT-1080 was stronger than that of CD13- alphavbeta3+ MDA-MB-435
      and much stronger than that of stable alphavbeta3-silencing MDA-MB-435. Our data
      indicated that the new AMPs containing NGR had potent antitumor activity against
      CD13+ or alphavbeta3+ tumor cells, preferably against CD13+ tumor cells, possibly
      through binding to CD13 or alphavbeta3 on tumor cells.

PMID- 25990456
TI  - Dual targeting of mTORC1 and mTORC2 by INK-128 potently inhibits human prostate
      cancer cell growth in vitro and in vivo.
AB  - Both mammalian target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are often
      over-activated in prostate cancer cells and are associated with cancer
      progression. In the current study, we evaluated the potential anti-prostate
      cancer activity of INK-128, an ATP-competitive mTORC1/2 dual inhibitor, both in
      vitro and in vivo. Our results showed that INK-128 exerted potent anti
      proliferative activity in established (PC-3 and LNCaP lines) and primary (patient
      derived) human prostate cancer cells by inducing cell apoptosis. The latter was
      evidenced by increase of annexin V percentage, formation of cytoplasmic histone
      associated DNA fragments, and cleavage of caspase-3. INK-128-induced prostate
      cancer cell apoptosis and cytotoxicity were alleviated upon pretreatment of cells
      with the pan-caspase inhibitor z-VAD-FMK or the specific caspase-3 inhibitor z
      DVED-FMK. At the molecular level, INK-18 blocked mTORC1/2 activation in PC-3
      cells and LNCaP cells and downregulated mTOR-regulated genes including cyclin D1,
      hypoxia-inducible factor 1alpha (HIF-1alpha), and HIF-2alpha. ERK-MAPK activation
      and androgen receptor expression were, however, not affected by INK-128
      treatment. In vivo, oral administration of INK-128 significantly inhibited growth
      of PC-3 xenografts in nude mice. The preclinical results of this study suggest
      that INK-128 could be further investigated as a promising anti-prostate cancer
      agent.

PMID- 25990457
TI  - Regulation of AURKC expression by CpG island methylation in human cancer cells.
AB  - AURKC, a member of the Aurora kinase gene family, is highly expressed in testis
      but is either moderately expressed or repressed in most somatic cells. Varying
      expression of AURKC has been observed in human cancers, but the underlying
      mechanisms of differential expression have been investigated only to a limited
      extent. We investigated the role of promoter CpG methylation in the regulation of
      AURKC gene expression in human cancer cells, in relation to a recently reported
      AURKC transcription repressor PLZF/ZBTB16, implicated in transformation and
      tumorigenesis. AURKC and PLZF/ZBTB16 expression profiles were investigated in
      reference to CpG methylation status on the AURKC promoter experimentally, and
      also in The Cancer Genome Atlas (TCGA) dataset involving multiple cancer types.
      AURKC promoter showed dense to moderate hypermethylation correlating with low to
      moderate expression of the gene in normal somatic cells and cancer cell lines,
      while testis with high expression revealed marked hypo-methylation. Treatment
      with the demethylating agent, 5-aza-dC, but not the histone deacetylase (HDAC)
      inhibitor, TSA, led to elevated expression in cancer cell lines, indicating that
      promoter DNA methylation negatively regulates AURKC expression. High expression
      of PLZF in PLZF-transfected cells treated with 5-aza-dC only partially repressed
      expression of AURKC despite 5-aza-dC also inducing elevated PLZF expression.
      Analyses of the TCGA data showed differential expression of AURKC in multiple
      cancer types and stronger correlation of AURKC expression with CpG methylation
      compared to PLZF levels. These findings demonstrate that differential promoter
      CpG methylation is an important mechanism regulating AURKC expression in cancer
      cells.

PMID- 25990458
TI  - A combinatory use of adenoviruses expressing melanoma differentiation-associated
      gene-7 and replication-competent adenoviruses produces synergistic effects on
      pancreatic carcinoma cells.
AB  - Type 5 adenoviruses expressing mda-7 gene (Ad-mda-7) induced cell death in
      various kinds of human tumors, but pancreatic carcinoma cells were relatively
      resistant to Ad-mda-7-mediated cytotoxicity. We then examined whether infection
      of Ad-mda-7 together with replication-competent Ad produced combinatory cytotoxic
      effects. We prepared replication-competent Ad, defective of the E1B55kDa gene or
      activated by a transcriptional regulatory region of the midkine or the survivin
      gene of which the expression was up-regulated in human tumors. Type 5 Ad bearing
      the exogenous regulatory region were further modified by replacing the fiber-knob
      region with that of type 35 Ad. Pancreatic carcinoma cells were infected with
      replication-incompetent Ad-mda-7 and the replication-competent Ad. Combinatory
      effects were examined with the CalcuSyn software and cell cycle analyses. Ad-mda
      7 and the replication-competent Ad achieved cytotoxicity to pancreatic carcinoma.
      A combinatory use of Ad-mda-7 and either Ad defective of the E1B55kDa gene or Ad
      activated by the regulatory region produced synergistic cytotoxic effects. Cell
      cycle analyses demonstrated that the combination increased sub-G1 populations.
      These data collectively suggest that expression of MDA-7 augments cytotoxicity of
      replication-competent Ad and achieves adjuvant effects on Ad-mediated cell death.

PMID- 25990459
TI  - MicroRNA expression profiles in muscle-invasive bladder cancer: identification of
      a four-microRNA signature associated with patient survival.
AB  - Bladder cancer ranks the second most common genitourinary tract cancer, and
      muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all
      bladder cancer cases with high mortality. In the current study, with a total of
      202 treatment-naive primary MIBC patients identified from The Cancer Genome Atlas
      dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression
      profiles in MIBC, with the aim to investigate the relationship of miRNA
      expression with the progression and prognosis of MIBC, and generate a miRNA
      signature of prognostic capabilities. In the progression-related miRNA profiles,
      a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and
      histologic grade, respectively. Of the eight most important progression-related
      miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly
      associated with survival of patients with MIBC. Finally, a four-miRNA signature
      was generated and proven as a promising prognostic parameter. In summary, this
      study identified the specific miRNAs associated with the progression and
      aggressiveness of MIBC and a four-miRNA signature as a promising prognostic
      parameter of MIBC.

PMID- 25990460
TI  - Impact of Spiritual Well-Being, Spiritual Perspective, and Religiosity on the
      Self-Rated Health of Jordanian Arab Christians.
AB  - The purpose of this study was to explore associations of spiritual well-being,
      spiritual perspective, and religiosity with self-rated health in a convenience
      sample of 340 adult Jordanian Arab Christians. Data were collected through church
      and community groups. Results indicated that spiritual well-being and religiosity
      were positively associated with self-rated health, but in the final regression
      model only spiritual well-being retained a significant association after
      controlling for the other spiritual and religious measures. In conclusion,
      spirituality and religiosity are important to Jordanian Arab Christians' health
      and well-being, and the implications for nursing practice are explored.

PMID- 25990462
TI  - Central Venous Catheter-Related Bloodstream Infections in Obese Hematologic
      Patients.

PMID- 25990463
TI  - Reply to investigating the relationship between vitamin d and cancer requires
      dosing the bioavailable nonhydroxylated vitamin d storage in cancer tissues.

PMID- 25990464
TI  - Plasmon coupling-enhanced two-photon photoluminescence of Au@Ag core-shell
      nanoparticles and applications in the nuclease assay.
AB  - Au and Ag nanoparticles (NPs) have been known to display significantly enhanced
      two-photon photoluminescence (2PPL) upon the formation of nanoparticle
      aggregates. The enhancement effect of the core-shell nanoparticles has not been
      explored so far. Here we have prepared Au@Ag bimetallic core-shell nanoparticles
      with different thicknesses (1.1, 2.1, 3.5, 4.5, and 5.5 nm) of silver coating on
      19 nm Au NPs to investigate the composition effects on plasmon coupling-enhanced
      2PPL. A maximum 2PPL enhancement factor (IcoupledNPs/IisolatedNPs) of up to 840
      fold was obtained for Au@Ag NPs with ~3.5 nm Ag nanoshells. These Au@Ag NPs were
      subsequently utilized in two-photon detection of S1 nuclease as a
      photoluminescence turn on probe. This method displayed high sensitivity with the
      limit of detection of 1.4 * 10(-6) U MUL(-1) and an excellent selectivity. 

PMID- 25990461
TI  - Monocyte trafficking across the vessel wall.
AB  - Monocytes fundamentally contribute to immune surveillance and the inflammatory
      response in immunoinflammatory diseases like atherosclerosis. Recruitment of
      these cells to the site of injury requires their trafficking across the blood
      vessel wall. A series of events, including capture, rolling, slow rolling,
      arrest, adhesion strengthening, and lateral locomotion, precede monocyte
      transmigration. Recent investigations have revealed new aspects of this cascade.
      This article revisits some conventional paradigms and selectively highlights new
      findings, including novel insights into monocyte differentiation and recently
      identified functional mediators, signalling pathways, and new structural aspects
      of monocyte extravasation. The emerging roles of endothelial junctional molecules
      like vascular endothelial-cadherin and the junctional adhesion molecule family,
      adhesion molecules such as intercellular adhesion molecule-1, molecules localized
      to the lateral border recycling compartment like cluster of differentiation 99,
      platelet/endothelial cell adhesion molecule-1, and poliovirus receptor (CD155),
      as well as other cell surface molecules such as cluster of differentiation 146
      and ephrins in transendothelial migration are discussed. 

PMID- 25990465
TI  - Pulse-dose radiofrequency can reduce chronic pain in trapezio-metacarpal
      osteoarthritis: A mini-invasive therapeutic approach.
AB  - AIM: To assess the efficiency of pulse-dose radiofrequency (PDRF) in the
      management of chronic pain in patients with trapezio-metacarpal osteoarthritis
      (OA). METHODS: Seventy-five patients with trapezio-metacarpal OA were treated
      with the PDRF between October 2011 and September 2013. A 22-gauge cannula with a
      5-cm length was introduced with percutaneous access in the lateral region of the
      affected trapezio-metacarpal joint. The PDRF procedure was performed with 1200
      pulses at 45 V and 20 msec duration, followed by a 480 msec silent phase. The
      follow-up visits were performed at 1 month, 3 and 6 months after the PDRF
      procedure. All patients underwent a second treatment between 7 and 9 months after
      the first PDRF procedure with a new follow-up scheme at 1, 3, 6 and 9 months.
      RESULTS: Mean visual analogue scale (VAS) scores before the procedures was 8.5 +/
      1.1. A great reduction in pain intensity was reported at 3 months after the PDRF
      procedure (mean VAS scores 3.1 +/- 0.9, P < 0.05). Pain intensity began to
      increase back to pre-procedural values after 4 months (mean VAS scores at 6
      months was 7.9 +/- 1.3, P < 0.05). After the second PDRF treatment the mean VAS
      scores decreased to 3.3 +/- 0.8 at 3 months, but increased to 8.1 +/- 1.6 at 9
      months. (P < 0.05). No complications after the procedures were observed.
      CONCLUSIONS: The PDRF may be a safe, repeatable and effective short-term pain
      management technique in patients with trapezio-metacarpal OA. Larger, randomized
      controlled studies are indicated to better clarify the efficacy and utility of
      the PDRF.

PMID- 25990466
TI  - Integrating virtual dermatopathology as part of formative and summative
      assessment of residents: a feasibility pilot study.

PMID- 25990467
TI  - Do all the patients with vitamin B12 deficiency have pernicious anemia?
AB  - BACKGROUND: Vitamin B12 deficiency may result in pernicious anemia (PA). This
      study evaluated whether all the patients with vitamin B12 deficiency had PA.
      METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and
      homocysteine concentrations and mean corpuscular volume (MCV) in 90 vitamin B12
      deficient patients were measured and compared with the corresponding data in 180
      age- and sex-matched healthy control subjects. PA was defined by World Health
      Organization (WHO) as having an Hb concentration <13 g/dl for men and <12 g/dl
      for women, an MCV ? 100 fl, a serum vitamin B12 level <200 pg/ml, and serum
      gastric parietal cell antibody (GPCA) positivity. RESULTS: We found that 35
      (38.9%) and 20 (22.2%) patients with vitamin B12 deficiency had deficiencies of
      Hb (men <13 g/dl, women <12 g/dl) and iron (<60 MUg/dl), respectively. Moreover,
      65 (72.2%) and 37 (41.1%) patients with vitamin B12 deficiency had abnormally
      high blood homocysteine level (>12.7 MUM) and high MCV (?100 fl), respectively.
      In addition, 43 (47.8%) vitamin B12-deficient patients with had GPCA positivity.
      Patients with vitamin B12 deficiency had a significantly higher frequency of Hb
      or iron deficiency, of abnormally elevated blood homocysteine level or high MCV,
      and of GPCA positivity than healthy control subjects (all P-values < 0.001).
      However, only 17 (18.9%) of 90 vitamin B12-deficient patients were diagnosed as
      having PA by the WHO definition. CONCLUSION: Only 18.9% of patients with vitamin
      B12 deficiency are discovered to have PA by the WHO definition.

PMID- 25990468
TI  - Gradient CdSe/CdS Quantum Dots with Room Temperature Biexciton Unity Quantum
      Yield.
AB  - Auger recombination is a major limitation for the fluorescent emission of quantum
      dots (QDs). It is the main source of QDs fluorescence blinking at the single
      particle level. At high-power excitation, when several charge carriers are formed
      inside a QD, Auger becomes more efficient and severely decreases the quantum
      yield (QY) of multiexcitons. This limits the efficiency and the use of colloidal
      QDs in applications where intense light output is required. Here, we present a
      new generation of thick-shell CdSe/CdS QDs with dimensions >40 nm and a
      composition gradient between the core and the shell that exhibits 100% QY for the
      emission of both the monoexciton and the biexciton in air and at room temperature
      for all the QDs we have observed. The fluorescence emission of these QDs is
      perfectly Poissonian at the single-particle level at different excitation levels
      and temperatures, from 30 to 300 K. In these QDs, the emission of high-order (>2)
      multiexcitons is quite efficient, and we observe white light emission at the
      single-QD level when high excitation power is used. These gradient thick shell
      QDs confirm the suppression of Auger recombination in gradient core/shell
      structures and help further establish the colloidal QDs with a gradient shell as
      a very stable source of light even under high excitation. 

PMID- 25990469
TI  - Human embryonic stem cell-derived cardiac progenitors for severe heart failure
      treatment: first clinical case report.
AB  - AIMS: Comparative studies suggest that stem cells committed to a cardiac lineage
      are more effective for improving heart function than those featuring an extra
      cardiac phenotype. We have therefore developed a population of human embryonic
      stem cell (ESC)-derived cardiac progenitor cells. METHODS AND RESULTS:
      Undifferentiated human ESCs (I6 line) were amplified and cardiac-committed by
      exposure to bone morphogenetic protein-2 and a fibroblast growth factor receptor
      inhibitor. Cells responding to these cardio-instructive cues express the cardiac
      transcription factor Isl-1 and the stage-specific embryonic antigen SSEA-1 which
      was then used to purify them by immunomagnetic sorting. The Isl-1(+) SSEA-1(+)
      cells were then embedded into a fibrin scaffold which was surgically delivered
      onto the infarct area in a 68-year-old patient suffering from severe heart
      failure [New York Heart Association [NYHA] functional Class III; left ventricular
      ejection fraction (LVEF): 26%]. A coronary artery bypass was performed
      concomitantly in a non-infarcted area. The implanted cells featured a high degree
      of purity (99% were SSEA-1(+)), had lost the expression of Sox-2 and Nanog, taken
      as markers for pluripotency, and strongly expressed Isl-1. The intraoperative
      delivery of the patch was expeditious. The post-operative course was
      uncomplicated either. After 3 months, the patient is symptomatically improved
      (NYHA functional Class I; LVEF: 36%) and a new-onset contractility is
      echocardiographically evident in the previously akinetic cell/patch-treated, non
      revascularized area. There have been no complications such as arrhythmias, tumour
      formation, or immunosuppression-related adverse events. CONCLUSION: This
      observation demonstrates the feasibility of generating a clinical-grade
      population of human ESC-derived cardiac progenitors and combining it within a
      tissue-engineered construct. While any conclusion pertaining to efficacy would be
      meaningless, the patient's functional outcome yet provides an encouraging hint.
      Beyond this case, the platform that has been set could be useful for generating
      different ESC-derived lineage-specific progenies.

PMID- 25990471
TI  - Manufacturing a nanowire-based sensing system via flow-guided assembly in a
      microchannel array template.
AB  - A novel flow-guided assembly approach is presented to accurately align and
      position nanowire arrays in pre-defined locations with high throughput and large
      scale manufacturing capability. In this approach, a polymer solution is first
      filled in an array of microfluidic channels. Then a gas flow is introduced to
      blow out most of the solution while pushing a little leftover against the channel
      wall for assembly into polymer nanowires. In this way, highly ordered nanowires
      are conveniently aligned in the flow direction and patterned along both sides of
      the microchannels. In this study, we demonstrated this flow-guided assembly
      process by producing millimetre-long nanowires across a 5 * 12 mm area in the
      same orientation and with basic 'I-shape', 'T-shape', and 'cross' patterns. The
      assembled polymer nanowires were further converted to conductive carbon nanowires
      through a standard carbonization process. After being integrated into electronic
      sensors, high sensitivity was found in model protein sensing tests. This new
      nanowire manufacturing approach is anticipated to open new doors to the
      fabrication of nanowire-based sensing systems and serve as good manufacturing
      practice for its simplicity, low cost, alignment reliability, and high
      throughput. 

PMID- 25990470
TI  - PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling.
AB  - Teriparatide, a recombinant peptide corresponding to amino acids 1-34 of human
      parathyroid hormone (PTH), has been an effective bone anabolic drug for over a
      decade. However, the mechanism whereby PTH stimulates bone formation remains
      incompletely understood. Here we report that in cultures of osteoblast-lineage
      cells, PTH stimulates glucose consumption and lactate production in the presence
      of oxygen, a hallmark of aerobic glycolysis, also known as Warburg effect.
      Experiments with radioactively labeled glucose demonstrate that PTH suppresses
      glucose entry into the tricarboxylic acid cycle (TCA cycle). Mechanistically, the
      increase in aerobic glycolysis is secondary to insulin-like growth factor (Igf)
      signaling induced by PTH, whereas the metabolic effect of Igf is dependent on
      activation of mammalian target of rapamycin complex 2 (mTORC2). Importantly,
      pharmacological perturbation of glycolysis suppresses the bone anabolic effect of
      intermittent PTH in the mouse. Thus, stimulation of aerobic glycolysis via Igf
      signaling contributes to bone anabolism in response to PTH.

PMID- 25990472
TI  - Falling asleep at the wheel across Europe.

PMID- 25990473
TI  - [Pseudoachalasia in a patient with a history of non-Hodgkin lymphoma].

PMID- 25990475
TI  - Antimicrobial resistance is a social problem requiring a social solution.

PMID- 25990474
TI  - An integrative analysis of post-translational histone modifications in the marine
      diatom Phaeodactylum tricornutum.
AB  - BACKGROUND: Nucleosomes are the building blocks of chromatin where gene
      regulation takes place. Chromatin landscapes have been profiled for several
      species, providing insights into the fundamental mechanisms of chromatin-mediated
      transcriptional regulation of gene expression. However, knowledge is missing for
      several major and deep-branching eukaryotic groups, such as the Stramenopiles,
      which include the diatoms. Diatoms are highly diverse and ubiquitous species of
      phytoplankton that play a key role in global biogeochemical cycles. Dissecting
      chromatin-mediated regulation of genes in diatoms will help understand the
      ecological success of these organisms in contemporary oceans. RESULTS: Here, we
      use high resolution mass spectrometry to identify a full repertoire of post
      translational modifications on histones of the marine diatom Phaeodactylum
      tricornutum, including eight novel modifications. We map five histone marks
      coupled with expression data and show that P. tricornutum displays both unique
      and broadly conserved chromatin features, reflecting the chimeric nature of its
      genome. Combinatorial analysis of histone marks and DNA methylation demonstrates
      the presence of an epigenetic code defining activating or repressive chromatin
      states. We further profile three specific histone marks under conditions of
      nitrate depletion and show that the histone code is dynamic and targets specific
      sets of genes. CONCLUSIONS: This study is the first genome-wide characterization
      of the histone code from a stramenopile and a marine phytoplankton. The work
      represents an important initial step for understanding the evolutionary history
      of chromatin and how epigenetic modifications affect gene expression in response
      to environmental cues in marine environments.

PMID- 25990476
TI  - Systematic pelvic and paraaortic lymphadenectomy in early high-risk or advanced
      endometrial cancer.
AB  - PURPOSE: Patients with high-risk early or advanced endometrial cancer (EC) are at
      high risk for lymph node (LN) metastases. However, both the anatomical pattern of
      the LN metastases and also the therapeutic value of systematic LN dissection
      remain a field of discussion and controversy. METHODS: We performed an
      exploratory analysis of patients with high-risk or advanced EC who underwent
      systematic pelvic and para-aortic lymphadenectomy in two tertiary referral
      centers for gynecological malignancies. RESULTS: One hundred and twenty-eight
      completely surgically staged patients underwent systematic pelvic and para-aortic
      lymphadenectomy for high-risk or advanced EC. A median of 29 and 21.5 LN was
      harvested in the pelvis and in the para-aortic region, respectively. Overall, 27
      patients (21.1 %) had positive LN: 18 % showed positive pelvic LN and 14.8 %
      positive para-aortic LN; while 3.1 % showed isolated para-aortic LN metastases.
      Five-year overall survival was 70 versus 30 % in LN-negative versus LN-positive
      patients (p < 0.01). LN-status was the only factor significantly associated with
      overall survival [HR: 3.67 (95 % CI 1.48-9.11); p = 0.01] in a multivariate Cox
      regression model. CONCLUSIONS: Patients with high-risk or advanced EC were at a
      high-risk for LN metastases. Anatomical distribution of positive LN indicates
      that lymphadenectomy, when performed, should contain both pelvic and para-aortic
      areas up to the renal vessels for an accurate assessment of all potential
      positive LN.

PMID- 25990477
TI  - Myo-inositol is a promising treatment for the prevention of ovarian
      hyperstimulation syndrome (OHSS): an animal study.
AB  - PURPOSE: To evaluate the efficacy of myo-inositol (MI) pretreatment in OHSS.
      METHODS: In this experimental OHSS rat model, 42 immature Wistar albino female
      rats were divided into 6 groups: (1) the control group, (2) the ovarian
      stimulation group, (3) the OHSS group, (4) the OHSS + Metformin group, (5) OHSS +
      MI group, (6) OHSS + Metformin + MI group. OHSS was established after treatment
      with metformin and myo-inositol for 14 days, in the meanwhile the treatment of
      metformin and myo-inositol was also continued. All animals were killed 48 h after
      hCG administration and were compared in terms of vascular permeability, ovarian
      weight and diameter, ovarian VEGF, COX-2 and PEDF expression
      (immunohistochemistry), serum PEDF and estradiol (E2) levels. RESULTS: Vascular
      permeability, VEGF and COX-2 expressions were reduced in animals treated with MI
      and/or metformin. While PEDF expression was increased in the groups taking
      metformin, there was no difference in PEDF expression in the group taking MI and
      OHSS group. There was no significant difference in serum PEDF levels between
      groups. Blood E2 levels were decreased in groups treated with MI or metformin
      compared to the OHSS group. CONCLUSIONS: Our data demonstrate that myo-inositol
      is effective in preventing OHSS, similar to metformin. Although the two drugs are
      thought to act through distinct mechanisms, there is no apparent benefit to co
      treatment with both drugs in an animal model of OHSS. Administration of myo
      inositol prior to IVF treatment may favor the control of ovulation induction.
      Further studies are necessary to elucidate the mechanism of action and further
      support our findings.

PMID- 25990478
TI  - Gut satiety hormones and hyperemesis gravidarum.
AB  - Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and
      vomiting during pregnancy. Some gut hormones that regulate appetite may have
      important role in etiopathogenesis of HG and weight changes during pregnancy. In
      this study, levels of gut satiety hormones were evaluated in pregnant women with
      HG. METHODS: This prospective case-control study was conducted in 30 women with
      HG and 30 healthy pregnant women without symptoms of HG. Fasting venous blood
      samples were taken from all subjects for measurement of plasma gut hormone
      levels; obestatin (pg/mL), peptide YY (PYY), pancreatic polypeptide (PP) and
      cholecystokinin (CCK). RESULTS: Plasma PYY and PP levels were significantly
      higher in HG group. The most important parameter in diagnosis of HG was plasma PP
      level. Simple use of PP level led to the diagnosis 91.1 % of HG cases correctly.
      The single most important parameter in the prediction of HG was also PP level.
      CONCLUSION: Anorexigenic gut hormones might have important role in
      etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy.

PMID- 25990479
TI  - Prevalence of human papillomavirus infection in pregnant versus non-pregnant
      women in Brazil.
AB  - PURPOSE: To investigate the prevalence of human papillomavirus (HPV) in cervical
      samples of pregnant and non-pregnant women in South-Brazil. METHODS: A
      prospective study of 91 pregnant and 92 non-pregnant women with no previous
      history of cervical dysplasia or cancer was carried out. Cervical samples for HPV
      testing and cytology were collected in each trimester of pregnancy and in the
      puerperium for pregnant women and at matched intervals for the non-pregnant
      women. All samples were analyzed through PCR with consensus primers GP5+/GP6+.
      Genotyping was performed using specific primers. To control for confounding
      factors, the analysis of multivariate logistic regression was applied. The
      measure of odds ratio (OR) and the 95 % confidence interval (95 % CI) were used.
      The level of statistical significance was set at 5 % (P <= 0.05). RESULTS: HPV
      DNA was detected in 23/91 (25.3 %) cervical samples from the pregnant women and
      in 12/92 (13 %) cervical samples from non-pregnant women (P = 0.035). There was a
      significant association among cervical HPV infection and young age, number of
      lifetime sexual partners, and the presence of abnormal cervical cytology. HPV16
      and HPV18 were the viral types more frequently detected. Out of the 23 HPV
      positive pregnant women, 17 (73.9 %) had normal cervical cytology. CONCLUSION:
      Our results suggest a higher prevalence of HPV infection in pregnant vs. non
      pregnant women. This finding may be related to the relative immunosuppression
      observed in pregnant women, outlining the importance of the appropriate
      monitoring of the viral infection in this specific population.

PMID- 25990480
TI  - Comparison of dienogest versus triptorelin acetate in premenopausal women with
      adenomyosis: a prospective clinical trial.
AB  - PURPOSE: To compare the efficacy of the oral dienogest versus triptorelin acetate
      injection for treatment of premenopausal menorrhagia and pelvic pains in women
      with uterine adenomyosis. METHODS: A total of 41 patients with adenomyosis
      suffering from pelvic pains and menorrhagia were recruited. First group was
      managed with oral dienogest (2 mg/day, orally) while the second group received
      triptorelin acetate (3.75 mg/4 weeks, subcutaneous injection) for 16 weeks.
      Outpatient follow-up was undertaken after 8 weeks but mean values were calculated
      at baseline and after 16 weeks (end of treatment). RESULTS: A total of 41 women
      were allocated to treatment with dienogest (n = 22) or triptorelin acetate (n =
      19); 19 (86.4 %) and 18 (94.7 %) % of the respective groups completed the trial.
      Significant reductions in pelvic pains after 16 weeks treatment were obtained in
      both groups demonstrating the equivalence of dienogest relative to triptorelin
      acetate. Triptorelin acetate was more effective in controlling of menorrhagia and
      reduction of uterine volume. CONCLUSIONS: Dienogest may be a valuable alternative
      to depot triptorelin acetate for treatment of premenopausal pelvic pains in women
      with uterine adenomyosis.

PMID- 25990482
TI  - A randomized controlled trial of sublingual misoprostol and intramuscular
      oxytocin for prevention of postpartum hemorrhage.
AB  - PURPOSE: In India, two third of maternal deaths occur in rural areas where there
      is lack of transportation facilities, lack of refrigeration to store the
      injectable uterotonic drug such as oxytocin, lack of skilled personnel to
      administer them and lack of sterile syringes and needles. Hence, this study was
      conceived to evaluate misoprostol as a safe, effective, easily administered non
      parenteral drug in the prevention of postpartum hemorrhage. METHODS: This study
      was conducted during the period from August 2012 to July 2014. Low risk women
      with singleton pregnancy at term admitted for vaginal delivery were eligible for
      the study. A total of 500 women were randomized to two groups, 250 in each group,
      either to receive 400 mcg misoprostol sublingually or 10 units oxytocin
      intramuscularly at the delivery of anterior shoulder. Patient factors, labor
      parameters, blood loss and side effects were noted. RESULTS: The women in both
      the groups were well matched with respect to age, parity, gestational age and
      labor parameters. There was statistical significance in the blood loss (p = 0.04)
      between the two groups. The average blood loss was 70 ml in misoprostol group and
      75 ml in oxytocin group. Shivering was the statistically significant side effect
      (p = 0.004) in the misoprostol group and nausea was the statistically significant
      side effect (p = 0.003) in the oxytocin group. CONCLUSIONS: Sublingual
      misoprostol is as effective as intramuscular oxytocin as a prophylactic oxytocic
      in the active management of third stage of labor for prevention of postpartum
      hemorrhage.

PMID- 25990483
TI  - Erratum to: Proteomic Analysis of the Defense Response of Wheat to the Powdery
      Mildew Fungus, Blumeria graminis f. sp. tritici.

PMID- 25990481
TI  - Long-term outcomes of antenatal corticosteroids treatment in very preterm infants
      after chorioamnionitis.
AB  - PURPOSE: To evaluate the effect of antenatal corticosteroids (AC) therapy on
      short- and long-term outcomes among very low birth weight preterm infants after
      histologic chorioamnionitis (HCA). METHODS: We performed a retrospective analysis
      of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6
      weeks of gestation between 2003 and 2007, who registered to the Neonatal Research
      Network Japan. The effects of AC therapy on mortality, neurodevelopmental
      outcomes at 3 years of age and neonatal morbidities were analyzed in the groups
      with or without HCA using logistic regression analysis. RESULTS: In the study
      subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded
      without data for HCA. AC therapy was significantly associated with decreasing
      mortality before 3 years of age; [0.52 (0.32-0.86)], [odds ratio (95 % confidence
      intervals]. There were no differences between the two groups regarding
      neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41-1.99)],
      development quotient <70 [0.93 (0.48-1.81)], visual impairment [0.46 (0.04
      5.18)], and severe hearing impairment [4.00 (0.30-53.4)] in the group with HCA as
      well as without HCA. Regarding neonatal morbidities, AC therapy was associated
      with a lower incidence of respiratory distress syndrome [0.67 (0.50-0.91)],
      sepsis [0.62 (0.41-0.94)], late-onset adrenal insufficiency [0.62 (0.39-0.98)]
      and an increased incidence of chronic lung disease [1.62 (1.18-2.24)] in the
      group with HCA. In the group without HCA, AC therapy was associated with
      decreasing respiratory distress syndrome [0.60 (0.43-0.84)] and increasing
      chronic lung disease [1.34 (1.11-1.62)]. CONCLUSION: AC therapy is significantly
      associated with reduced mortality before 3 years of age in VLBW infants with HCA,
      but not with neurodevelopmental outcomes, which was same as the results found in
      infants without HCA. AC therapy is recommended for women with suspected
      chorioamnionitis, as well as those without chorioamnionitis.

PMID- 25990484
TI  - Identification of Ellagitannins and Flavonoids from Eugenia brasilienses Lam.
      (Grumixama) by HPLC-ESI-MS/MS.
AB  - The grumixama (Eugenia brasiliensis Lam.), also known as Brazilian cherry, is a
      fruit native to Brazil. This study identified the flavonoids in the flesh and
      seeds and ellagitannin in the flesh of purple and yellow varieties. The
      physicochemical characteristics and antioxidant capacity of these fruits were
      also evaluated. Anthocyanins and flavonols were found in high levels in the flesh
      of purple (32-180 mg 100 g(-1) FW) and yellow grumixama (13-41 mg 100 g(-1) FW),
      respectively. The major flavonoids identified were cyanidin 3-glucoside and
      quercetin aglycone. Furthermore, ellagitannins were found in high levels in the
      flesh of purple (82-243 mg ellagic acid equiv 100 g(-1) FW) and yellow grumixama
      (92 mg ellagic acid equiv 100 g(-1) FW) and seeds (2220-2905 mg ellagic acid
      equiv 100 g(-1) FW). The ellagitannin profiles of both varieties were first
      characterized in which pedunculagin isomers, strictinin isomers, and ellagic acid
      galloyl hexoside were the major ellagitannins identified. In summary, both
      varieties of the grumixama fruit as well as the seeds could be good sources of
      bioactive compounds, mainly ellagitannins. 

PMID- 25990485
TI  - Influence of the previous use of beta-blockers on the early clinical course of
      acute coronary syndromes.
AB  - Recent studies have recently questioned the current role of beta-blockers in
      myocardial infarction. Our purpose is to analyze the influence of the previous
      use of beta-blockers on the early course of patients admitted because of acute
      coronary syndrome (ACS). We analyzed the data of 37.359 patients included in the
      ARIAM-Andalucia Registry. Of them, 7759 (20.8%) were previously receiving beta
      blockers. BB patients were older, more often female, had more risk factors and
      vascular disease, and less often had an ST-elevation myocardial infarction. In
      the unadjusted analysis, BB patients less often had ventricular fibrillation or
      atrioventricular block, and more often a Killip classification >1, and no
      difference of in-hospital mortality (5.7 vs 5.6%). After logistic regression
      analysis and propensity score matching, no differences in complications or
      mortality (odds ratio 0.997, 95% confidence interval 0.882-1.128) were found in
      relationship to previous beta-blockers. In conclusion, we find that the previous
      administration of beta-blockers is not an independent predictor of the early
      prognosis of ACS.

PMID- 25990486
TI  - How far from correct is the use of adrenaline auto-injectors? A survey in Italian
      patients.
AB  - Self-administered adrenaline through an auto-injector is the main out-of-hospital
      treatment for anaphylaxis, and patients should be trained to promptly and
      correctly use the device. The aim of the study was to verify the proper use of
      the device and the correct drug administration, and to identify possible misuse
      by patients. In seven Italian Allergy clinics, patients who were previously
      provided with self-injectable adrenaline were recruited at the follow-up visit
      required for the renewal of their prescription. All patients completed a
      questionnaire covering details of their allergic reactions, and knowledge of the
      device. The correct use was verified by the physician using a trainer with a four
      step examination. 242 patients were included; 46 patients (18 %) did not always
      carry the auto-injector, and 35 patients (14 %) reported situations in which they
      were doubtful about whether to use adrenaline. Only 39 % of patients properly
      managed the device, while some patients (6 %) failed in all four steps. The
      majority of patients considered it appropriate to use adrenaline at the onset of
      respiratory symptoms (56 %). The factor most closely related to proper use of the
      device was the education of the patient (p = 0.03), while age and the time from
      first prescription did not affect the ability to properly use the auto-injector.
      Even though accurate training is conducted, many patients are still unable to
      properly use the adrenaline auto-injector in case of anaphylaxis. Allergists
      should review the instructions provided to the patients every time a renewal of
      the auto-injector is prescribed.

PMID- 25990487
TI  - Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and
      review of the literature.
AB  - INTRODUCTION: Fibrinogen storage disease (FSD) is characterized by
      hypofibrinogenemia and hepatic inclusions due to impaired release of mutant
      fibrinogen which accumulates and aggregates in the hepatocellular endoplasmic
      reticulum. Liver disease is variable. AIM: We studied a new Swiss family with
      fibrinogen Aguadilla. In order to understand the molecular peculiarity of FSD
      mutations, fibrinogen Aguadilla and the three other causative mutations, all
      located in the gammaD domain, were modelled. METHOD: The proband is a Swiss girl
      aged 4 investigated because of fatigue and elevated liver enzymes. Protein
      structure models were prepared using the Swiss-PdbViewer and POV-Ray software.
      RESULTS: The proband was found to be heterozygous for fibrinogen Aguadilla: FGG
      Arg375Trp. Familial screening revealed that her mother and maternal grandmother
      were also affected and, in addition, respectively heterozygous and homozygous for
      the hereditary haemochromatosis mutation HFE C282Y. Models of backbone and side
      chain interactions for fibrinogen Aguadilla in a 10-angstrom region revealed the
      loss of five H-bonds and the gain of one H-bond between structurally important
      amino acids. The structure predicted for fibrinogen Angers showed a novel helical
      structure in place of hole 'a' on the outer edge of gammaD likely to have a
      negative impact on fibrinogen assembly and secretion. CONCLUSION: The mechanism
      by which FSD mutations generate hepatic intracellular inclusions is still not
      clearly established although the promotion of aberrant intermolecular strand
      insertions is emerging as a likely cause. Reporting new cases is essential in the
      light of novel opportunities of treatment offered by increasing knowledge of the
      degradation pathway and autophagy.

PMID- 25990488
TI  - Exploration of the mechanisms of biofilm formation by Enterococcus faecalis in
      glucose starvation environments.
AB  - BACKGROUND: Enterococcus faecalis is the most common single species present in
      teeth after failed root canal therapy. This is mainly due to its ability to
      maintain viability for a long time in filled root canals where nutrients are
      normally sparse. The aim of this study was to explore the mechanism of E.
      faecalis survival and biofilm formation in glucose-starved environments. METHODS:
      Enterococcus faecalis ATCC 33186 was inoculated in energy starvation media for
      biofilm formation. Confocal laser scanning microscopy and fluorescent DNA-binding
      agents were employed to assess biofilm-forming ability. The physiochemical
      properties of the biofilm cell wall were investigated by measuring the
      hydrophobicity, extracellular polysaccharide and ATPase activity. The expression
      of stress and virulence genes was quantified by real-time quantitative polymerase
      chain reaction. RESULTS: The ability for biofilm formation decreased with a
      decreasing concentration of glucose. The cell surface hydrophobicity increased
      dramatically with decreasing glucose concentration. Water-soluble
      exopolysaccharide (WSE) synthesis decreased in glucose starvation media, whereas
      water-insoluble exopolysaccharide (WIE) synthesis increased. A marked decrease in
      ATPase activity was observed only in a no glucose medium. In addition,
      transcription of ace, fsrB and gelE genes increased under glucose starvation
      stress while atpE, salB and esp genes were down-regulated. CONCLUSIONS:
      Enterococcus faecalis survival and biofilm formation under glucose starvation
      stress may be attributed to an increase in cell-surface hydrophobicity and
      additionally to the up-regulation of some genes involved in stress response and
      biofilm formation. These characteristics may explain why E. faecalis can maintain
      viability for a long time in an energy-starved environment and why it is
      frequently isolated from persistently infected root canals.

PMID- 25990490
TI  - One-pot selective synthesis of a fullerene bisadduct for organic solar cell
      applications.
AB  - A single isomer of fullerene bisadduct, PC61PF, was obtained from commercially
      available fullerene derivative, PC61BM, in one pot over two steps. The tether
      directed remote functionalization approach provided a very simple and fast method
      to produce a single isomer of fullerene bisadduct with good yield and easy
      purification. Bulk heterojunction organic solar cells containing the bisadduct
      was fabricated and tested. 

PMID- 25990489
TI  - The impact of increasing dose on overall survival in prostate cancer.
AB  - PURPOSE: To assess the impact of increasing dose on overall survival (OS) for
      prostate cancer patients. METHODS: Treatment data were obtained on more than
      20,000 patients in the National Oncology Data Alliance(r), a proprietary database
      of merged tumor registries, who were treated for prostate cancer with definitive
      radiotherapy between 1995 and 2006. Eligible patients had complete data on total
      dose, T stage, use and timing of androgen deprivation therapy (ADT), and
      treatment start date (n = 20,028). Patients with prior malignancies were
      excluded. RESULTS: On multivariate analysis, dose, T stage, grade, marital
      status, age, and neoadjuvant ADT were significant predictors of OS. Hazard ratios
      for OS declined monotonically with increasing dose, reaching 0.63 (95 %
      Confidence Interval 0.53-0.76) at >=80 Gy. On subset analysis, neoadjuvant ADT
      significantly improved OS in high risk patients but was not significant in lower
      risk patients. The dose response was maintained across all risk groups. Medical
      comorbidities were balanced across all dose strata and sensitivity analysis
      demonstrated that other prognostic factors were unlikely to explain the observed
      dose response. CONCLUSIONS: This study suggests that increasing dose
      significantly improves OS in prostate cancer patients treated with radiotherapy.

PMID- 25990491
TI  - Finding unconscious phantasy in the session: Recognizing form.
AB  - The concept of unconscious phantasy has played - and still does play - a central
      role in psychoanalytic thinking. The author discusses the various forms by which
      unconscious phantasies manifest themselves in the analytic session as they are
      lived out and enacted in the transference relationship. This paper also aims at
      expanding the kleinian theory of symbol formation by exploring the impact that
      emotional aspects connected to early "raw', "pre-symbolic' phantasies have in the
      analysis and how their corporeal elements interlock with the signifying process.
      The author follows the expressive forms of primitive unconscious phantasies as
      they appear in a psychoanalytic session and proposes that the emotional effect
      that can be experienced in the communication between patient and analyst depends
      in great measure on "semiotic' aspects linked to primitive phantasies that are
      felt and lived out in embodied ways. Rather than a move from unconscious
      phantasies that typify symbolic equations to those showing proper symbolization,
      these can coexist and simultaneously find their way to what is communicated to
      the analyst. As early phantasies bear an intimate connection to the body and to
      unprocessed emotions when they are projected into the analyst they can produce a
      powerful resonance, sometimes also experienced in a physical way and forming an
      integral part of the analyst's counter-transference. 

PMID- 25990492
TI  - Need satisfaction, motivational regulations and exercise: moderation and
      mediation effects.
AB  - BACKGROUND: Based on the Self-determination theory process model, this study
      aimed to explore relationships between the latent constructs of psychological
      need satisfaction, autonomous motivation and exercise behaviour; the mediational
      role of autonomous motivation in the association of psychological need
      satisfaction with exercise behaviour; as well as gender and age differences in
      the aforementioned associations. METHODS: Adult active members of an Internet
      based exercise program (n = 1091) between 18 and 78 years of age completed a test
      battery on motivational aspects based on Self-determination theory. The Basic
      Psychological Needs in Exercise Scale and the Behavioural Regulation in Exercise
      Questionnaire-2 were used to measure need satisfaction and type of motivation and
      the Leisure Time Exercise Questionnaire to measure self-reported exercise.
      RESULTS: Need satisfaction predicted autonomous motivation, which in turn
      predicted exercise, especially for women. Autonomous motivation was found to
      mediate the association between need satisfaction and exercise. Age and gender
      moderated several of the paths in the model linking need satisfaction with
      motivation and exercise. CONCLUSION: The results demonstrated gender and age
      differences in the proposed sequential mechanisms between autonomous motivation
      and exercise in the process model. This study thus highlights a potential value
      in considering moderating factors and the need to further examine the underlying
      mechanisms between needs, autonomous motivation, and exercise behaviour.

PMID- 25990493
TI  - [Minimum effective concentration of bupivacaine for axillary brachial plexus
      block guided by ultrasound].
AB  - INTRODUCTION: The use of ultrasound in regional anesthesia allows reducing the
      dose of local anesthetic used for peripheral nerve block. The present study was
      performed to determine the minimum effective concentration (MEC90) of bupivacaine
      for axillary brachial plexus block (ABPB). METHODS: Patients undergoing hand
      surgery were recruited. To estimate the MEC90, a sequential up-down biased coin
      method of allocation was used. The bupivacaine dose was 5mL for each nerve
      (radial, ulnar, median, and musculocutaneous). The initial concentration was
      0.35%. This concentration was changed by 0.05% depending on the previous block: a
      blockade failure resulted in increased concentration for the next patient; in
      case of success, the next patient could receive or reduction (0.1 probability) or
      the same concentration (0.9 probability). Surgical anesthesia was defined as
      driving force <= 2 according to the modified Bromage scale, lack of thermal
      sensitivity and response to pinprick. Postoperative analgesia was assessed in the
      recovery room with numeric pain scale and the amount of drugs used within 4hours
      after the blockade. RESULTS: MEC90 was 0.241% [R2: 0.978, confidence interval:
      0.20%-0.34%]. No successful block patient reported pain after 4hours. CONCLUSION:
      This study demonstrated that ultrasound guided ABPB can be performed with the use
      of low concentration of local anesthetics, increasing the safety of the
      procedure. Further studies should be conducted to assess blockade duration at low
      concentrations.

PMID- 25990494
TI  - [Influence of preoperative propranolol on cardiac index during the anhepatic
      phase of liver transplantation].
AB  - INTRODUCTION: Liver transplantation (LT) is the best therapeutic option for end
      stage liver disease (ESLD). Non-selective beta-blocker medications such as
      propranolol act directly on the cardiovascular system (CVS) and are often used in
      the prevention of gastrointestinal bleeding resulting from HP. The effects of
      propranolol on CVS of cirrhotic patients during LT are not known. OBJECTIVE:
      Evaluate the influence of propranolol used preoperatively on cardiac index (CI)
      during the anhepatic phase of LT. METHOD: 101 adult patients (73 male [72.2%])
      who underwent cadaveric donor orthotopic liver transplantation by piggyback
      technique with preservation of the retrohepatic inferior vena cava performed at
      Hospital das Clinicas, Federal University of Minas Gerais were evaluated. There
      was no difference in severity between groups by the MELD system, p=0.70. The
      preoperative use of propranolol and the CI outcome were compared during the
      anhepatic phase of LT in 5 groups (I: increased CI, II: CI reduction lower than
      16%, III: CI reduction equal to or greater than 16% and less than 31%, IV: CI
      reduction equal to or greater than 31% and less than 46%, V: CI reduction equal
      to or greater than 46%). RESULTS: Patients in group I (46.4%) who received
      propranolol preoperatively were statistically similar to groups II (60%), III
      (72.7%), IV (50%) and V (30.8%), p=0.57. CONCLUSION: The use of propranolol
      before transplantation as prophylaxis for gastrointestinal bleeding may be
      considered safe, as it was not associated with worsening of CI in anhepatic phase
      of LT.

PMID- 25990495
TI  - [Bacterial colonization due to increased nurse workload in an intensive care
      unit].
AB  - INTRODUCTION: the rates of multiresistant bacteria colonization or infection
      (MRB+) development in intensive care units are very high. The aim of this study
      was to determine the possible association between the risk of development of
      nosocomial infections and increased daily nurse workload due to understaffing in
      intensive care unit. METHODS: we included 168 patients. Intensity of workload and
      applied procedures to patients were scored with the Project de Recherche en
      Nursing and the Omega scores, respectively. The criteria used for infections were
      those defined by the Centers for Disease Control. RESULTS: of the 168 patients,
      91 (54.2%) were female and 77 (45.8%) were male patients. The mean age of female
      and male was 64.9+/-6.2 years and 63.1+/-11.9 years, respectively. The mean
      duration of hospitalization in intensive care unit was 18.4+/-6.1 days.
      Multiresistant bacteria were isolated from cultures of 39 (23.2%) patients. The
      development of MRB+ infection was correlated with length of stay, Omega 1, Omega
      2, Omega 3, Total Omega, daily PRN, and Total PRN (p<0.05). There was no
      correlation between development of MRB+ infection with gender, age and Apache-II
      scores (p>0.05). CONCLUSION: the risk of nosocomial infection development in an
      intensive care unit is directly correlated with increased nurse workload, applied
      intervention, and length of stay. Understaffing in the intensive care unit is an
      important health problem that especially affects care-needing patients.
      Nosocomial infection development has laid a heavy burden on the economy of many
      countries. To control nosocomial infection development in the intensive care
      unit, nurse workload, staffing level, and working conditions must be arranged.

PMID- 25990496
TI  - [Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and
      lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized,
      double-blinded study].
AB  - BACKGROUND AND OBJECTIVES: Intraoperative use of opioids may be associated with
      postoperative hyperalgesia and increased analgesic consumption. Side effects due
      to perioperative use of opioids, such as postoperative nausea and vomiting may
      delay discharge. We hypothesized that total intravenous anesthesia consisting of
      lidocaine and dexmedetomidine as an opioid substitute may be an alternative
      technique for laparoscopic cholecystectomy and would be associated with lower
      fentanyl requirements in the postoperative period and less incidence of
      postoperative nausea and vomiting. METHODS: 80 Anesthesiologists I-II adults were
      scheduled for elective laparoscopic cholecystectomy. Patients were randomly
      allocated into two groups to have either opioid-free anesthesia with
      dexmedetomidine, lidocaine, and propofol infusions (Group DL) or opioid-based
      anesthesia with remifentanil, and propofol infusions (Group RF). All patients
      received a standard multimodal analgesia regimen. A patient controlled analgesia
      device was set to deliver IV fentanyl for 6h after surgery. The primary outcome
      variable was postoperative fentanyl consumption. RESULTS: Fentanyl consumption at
      postoperative 2nd hour was statistically significantly less in Group DL, compared
      with Group RF, which were 75+/-59MUg and 120+/-94MUg respectively, while it was
      comparable at postoperative 6th hour. During anesthesia, there were more
      hypotensive events in Group RF, while there were more hypertensive events in
      Group DL, which were both statistically significant. Despite higher recovery
      times, Group DL had significantly lower pain scores, rescue analgesic and
      ondansetron need. CONCLUSION: Opioid-free anesthesia with dexmedetomidine,
      lidocaine and propofol infusions may be an alternative technique for laparoscopic
      cholecystectomy especially in patients with high risk for postoperative nausea
      and vomiting.

PMID- 25990497
TI  - [Influence of different body positions in vital capacity in patients on
      postoperative upper abdominal].
AB  - RATIONALE: The changes in body position can cause changes in lung function, it is
      necessary to understand them, especially in the postoperative upper abdominal
      surgery, since these patients are susceptible to postoperative pulmonary
      complications. OBJECTIVE: To assess the vital capacity in the supine position
      (head at 0 degrees  and 45 degrees ), sitting and standing positions in patients
      in the postoperative upper abdominal surgery. METHODS: A cross-sectional study
      conducted between August 2008 and January 2009 in a hospital in Salvador/BA. The
      instrument used to measure vital capacity (VC) was analogic spirometer, the
      choice of the sequence of positions followed a random order obtained from the
      draw of the four positions. Secondary data were collected from the medical
      records of each patient. RESULTS: The sample consisted of 30 subjects with a mean
      age of 45.2+/-11.2 years, BMI 20.2+/-1.0 kg/m(2). The position on orthostasis
      showed higher values of CV regarding standing (mean change: 0.15+/-0.03 liters;
      p=0.001), the supine to 45 (average difference: 0.32+/-0.04 liters; p=0.001) and
      0 degrees  (0.50+/-0.05 liters; p=0.001). There was a positive trend between the
      values of FVC supine to upright posture (1.68+/-0.47; 1.86+/-0.48; 2.02+/-0.48
      and 2.18+/-0.52 liters; respectively). CONCLUSION: Body position affects the
      values of CV in patients in the postoperative upper abdominal surgery, increasing
      in postures where the chest is vertical.

PMID- 25990498
TI  - [What is missing for difficult airway management in the 21st century].

PMID- 25990499
TI  - Question 1: Is the use of furosemide beneficial in the treatment of acute kidney
      injury in the paediatric population including neonates?

PMID- 25990500
TI  - Management of developmental speech and language disorders. Part 2: acquired
      conditions.
AB  - Many children who present with these acquired impairments of communication have a
      clear preceding event such as an acquired brain injury from a road traffic
      accident. Children often respond differently in this situation to adult
      presentations. They may have a period of mutism when the prognosis might look
      poor and yet they subsequently make rapid progress and recover speech. They have
      greater potential for neural plasticity and language recovery, although they
      often have persisting difficulties in oral and written language. Alternatively,
      there may be a presentation with a paroxysmal event such as a seizure or a period
      of depressed consciousness, and the unusual behaviour that may accompany
      dysphasia and dysarthria may be misinterpreted in the child, whereas for the
      adult with the more common 'stroke-like' presentation, it would be immediately
      considered. Rarely the aphasia/dysphasia may itself be the paroxysmal event where
      actually recognising that the child's disrupted communication is the basis of any
      observed behaviours can be the greater challenge.

PMID- 25990501
TI  - What a general paediatrician needs to know about early life programming.
AB  - The process whereby early exposure to an adverse environment has an influence on
      later life outcomes has been called 'early life programming'. While
      epidemiological evidence for this has been available for decades, only in recent
      years have the mechanisms, in particular epigenetic modifications, for this
      process begun to be elucidated. We discuss the evidence for early life
      programming, the possible mechanisms, how effects may be transmitted across
      generations, and conclude by looking at some examples relevant to general
      paediatrics. 

PMID- 25990502
TI  - Preoperative Prediction of Lymph Node Status by Circulating Mir-18b and Mir-20a
      During Chemoradiotherapy in Patients with Rectal Cancer.
AB  - BACKGROUND: In locally advanced rectal cancer, therapeutic success of
      preoperative chemoradiotherapy (CRT) ranges from resistance to complete
      regression. For those patients that respond well to CRT, local resection (LR)
      procedures are currently under investigation to minimize surgical morbidity and
      to improve functional outcome. To maintain the oncologic benefit appropriate
      staging procedures are essential. However, current clinical assessment and
      imaging techniques need further improvement. METHODS: Five miRNAs associated with
      rectal cancer (miR-17, miR-18b, miR-20a, miR-31, and miR-193-3p) were analyzed in
      the plasma of rectal cancer patients (n = 42) using qPCR. Expression levels were
      assessed before, during and after CRT and analyzed in regard to patients' lymph
      node status obtained after total mesorectal excision and intensive
      histopathological work-up. RESULTS: Four of the five miRNAs revealed reliable
      results in the plasma. miR-31 was excluded due to its low expression. MicroRNA
      17, 18b, 20a, and 193-3p showed altering expression levels at different time
      points. Only 43% (miR-17), 43% (miR-18b), 53% (miR-20a), and 60% (miR-193-3p)
      showed a continuous in- or decrease of miRNA expression. The reduced expression
      of miR-18b and miR-20a during CRT was found to be significantly associated with
      postoperative lymph node negativity (p < 0.05). CONCLUSION: MicroRNA expression
      in patient plasma changes during preoperative CRT. The alteration is not
      continuous and the meaning requires additional analysis on a larger patient
      cohort. The co-occurrence of reduced miR-18b and miR-20a expression with lymph
      node negativity after preoperative CRT could help to stratify the surgical
      procedure with respect to total mesorectal excision and LR if validated
      prospectively.

PMID- 25990503
TI  - Lipophilicity study of eight cephalosporins by reversed-phase thin-layer
      chromatographic method.
AB  - The lipophilicity (R(M0)) and specific hydrophobic surface area for the
      representatives of four generation cephalosporins have been determined by
      reversed-phase thin-layer chromatography, and the effect of different mobile
      phase modifiers (such as methanol, acetonitrile, acetone, 1,4-dioxane and 2
      propanol) on the retention has been studied. The compounds studied showed typical
      retention behavior; their R(M) values decreased linearly with increasing
      concentration of the organic modifier in the eluent. The linear correlations
      between the volume fraction of the organic solvent and the R(M) values over a
      limited range were established for each solute, resulting in high values of
      correlation coefficients (>0.95 in most cases). R(M) values were determined by
      various concentrations of organic modifier, and the correlation obtained was
      extrapolated to 0% of organic modifier. Chromatographically established logP
      (R(M0)) parameters were compared with computationally calculated partition
      coefficients values (AClogP, ALOGP, KOWWIN, ALOGPs, XLOGP2, MLOGP and XLOGP3) and
      experimental octanol-water logP values (measured by the shake flask method). The
      received results demonstrate that RP-TLC may be a good alternative technique for
      analytics in describing the lipophilic nature of investigated cephalosporins as
      well as the activity.

PMID- 25990504
TI  - VEGF111b, a C-terminal splice variant of VEGF-A and induced by mitomycin C,
      inhibits ovarian cancer growth.
AB  - BACKGROUND: Alternative splicing of VEGF-A gives rise to two families - the pro
      angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family that differ by
      only six amino acids at their C-terminal end. The first verified and widely
      reported VEGFxxxb family member is VEGF165b, and here VEGF165b is a positive
      control. METHORDS: VEGF111b mRNA was detected in ovarian cancer cell lines SKOV3
      and OVCAR3 by RT-PCR. Western blot was used to detect VEGF111b and VEGF165b
      protein in the CMs and lysates of OVCAR3 cells. MTT and colony formation assay
      were used to detect the short-term and long-term proliferation inhibition ability
      of ovarian cancer cells with VEGF111b overexpression. Cell-cycle analysis was
      performed to further characterize VEGF111b inhibition effects. VEGF111b signaling
      on ovarian cancer cells were determined by western blot. The expression levels of
      Ki67, PCNA, CD31 and VEGF in VEGF111b overexpression xenograft model were
      detected by immunohistochemistry. RESULTS: Under the effect of mitomycin C, we
      identify a new member of VEGFxxxb family-VEGF111b in ovarian cancer cell lines.
      SKOV3 and OVCAR cells were transfected with empty lentivirus, VEGF111b or
      VEGF165b lentivirus. VEGF111b and VEGF165b overexpression inhibits proliferation
      of the ovarian cancer cells, but inhibition effect of VEGF111b is slightly less
      efficient than VEGF165b. Cell cycle analysis was further used to elucidate the
      mechanism involved in the inhibition effect. Further, we detected the expression
      of VEGF-R2 in SKOV3 and OVCAR3 cells, and shown that VEGF111b might bind to
      conventional VEGF-R2 with the results of reducing VEGF-R2 tyrosine
      phosphorylation and downstream signaling to have anti-tumor effects. In vivo
      VEGF111b overexpression inhibits ovarian cancer growth in xenograft mice.
      CONCLUSION: Our results show that VEGF111b, as a new member of VEGFxxxb family,
      with similar properties to VEGF165b, plays potent anti-tumor effect in vitro and
      in vivo that can target the VEGF-R2 and its signaling pathway to inhibit ovarian
      tumor growth. This also opens a new avenue for treating ovarian cancer.

PMID- 25990505
TI  - CMTM3 is reduced in prostate cancer and inhibits migration, invasion and growth
      of LNCaP cells.
AB  - PURPOSE: A novel tumor suppressor gene CKLF-like MARVEL transmembrane domain
      containing member 3 (CMTM3) is reduced or undetectable in many kinds of cancers
      and relates tumor malignant features. We detected its role in prostate cancer for
      possibility of target therapy as accumulating evidence has shown that CMTM3 is a
      promising tumor suppressor gene (TSG) for gene therapy. METHODS: The expression
      of CMTM3 detected in prostate tissue microarray, specimens and cell lines were
      evaluated by immunohistochemistry and semi-quantitative PCR and Western blot,
      respectively. After being transfected with CMTM3 adenovirus or vector (mock), the
      proliferation and migration and invasion of LNCaP cells were detected by
      transwell assay and matrigel assay, respectively. Furthermore, the effects of
      CMTM3 on tumor growth were performed in nude mice xenograft in vivo. RESULTS: We
      found CMTM3 was reduced in PCa tissues and cells compared with BPH tissues, and
      its expression in PCa tissues was related to the Gleason score. Moreover, after
      being transfected with adenovirus, ectopic expression of CMTM3 in LNCaP cells led
      to significant inhibition of cell proliferation and migration and invasion
      compared with the control (P < 0.05), which may be attributed to decreased Erk1/2
      activity as p-Erk1/2 was remarkably reduced when CMTM3 was overexpressed.
      Finally, restoration of CMTM3 significantly suppressed xenograft tumor growth in
      vivo (P < 0.01).

PMID- 25990506
TI  - Addition of bevacizumab to chemotherapy in patients with ovarian cancer: a
      systematic review and meta-analysis of randomized trials.
AB  - BACKGROUND: This systematic review and meta-analysis analyzed randomized
      controlled trials (RCTs) assessing the efficacy and tolerance of incorporating
      bevacizumab into chemotherapy in patients with advanced ovarian cancer. METHODS:
      MEDLINE, Web of Science, EMBASE and the Cochrane Central Register of Controlled
      Trials were reviewed for RCTs evaluating add-on bevacizumab in advanced ovarian
      cancer. Progression-free survival (PFS), overall survival (OS), objective
      response rate and adverse events were obtained from RCTs comparing first- and
      second-line bevacizumab plus chemotherapy with chemotherapy alone for advanced
      ovarian cancer. Meta-analyses were performed to determine hazard ratios for time
      to-event variables and odds ratios for dichotomous outcomes using random-effects
      or fixed-effects model based on the heterogeneity of included studies. RESULTS:
      Four RCTs, including 4246 patients, were identified and analyzed. Two trials,
      GOG218 and ICON7, assessing bevacizumab in first-line chemotherapy, found that
      bevacizumab significantly extended PFS (HR 0.82; 95% CI 0.75-0.89) and OS (HR
      0.86; 95% CI 0.75-0.99). The other two trials, OCEANS and AURELIA, analyzing
      second-line bevacizumab, found that this agent extended PFS (HR 0.48; 95% CI 0.41
      0.57), but did not enhance OS (HR 0.93; 95% CI 0.78-1.12). The most common
      adverse events associated with bevacizumab included hypertension, proteinuria and
      gastrointestinal perforation. CONCLUSION: The addition of bevacizumab to
      chemotherapy followed by bevacizumab significantly improved PFS and OS in
      frontline setting and PFS in recurrent settings compared with that of
      chemotherapy alone in patients with advanced ovarian cancer.

PMID- 25990508
TI  - Assessment of human sinus cavity air volume using tunable diode laser
      spectroscopy, with application to sinusitis diagnostics.
AB  - Sinusitis is a very common disease and improved diagnostic tools are desirable
      also in view of reducing over-prescription of antibiotics. A non-intrusive
      optical technique called GASMAS (GAs in Scattering Media Absorption
      Spectroscopy), which has a true potential of being developed into an important
      complement to other means of detection, was utilized in this work. Water vapor in
      the frontal sinuses, related to the free gas volume, was studied at around 937 nm
      in healthy volunteers. The results show a good stability of the GASMAS signals
      over extended times for the frontal sinuses for all volunteers, showing promising
      applicability to detect anomalies due to sinusitis. Measurements were also
      performed following the application of a decongestion spray. No noticeable signal
      change was observed, which is consistent with the fact that the water vapor
      concentration is given by the temperature only, and is not influenced by changes
      in cavity ventilation. Evaluated GASMAS data recorded on 6 consecutive days show
      signal stability for the left and right frontal sinus in one of the test
      volunteers.

PMID- 25990507
TI  - Efficacy of platinum combination chemotherapy after first-line gefitinib
      treatment in non-small cell lung cancer patients harboring sensitive EGFR
      mutations.
AB  - PURPOSE: Gefitinib is an effective first-line chemotherapy for advanced non-small
      cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However,
      whether second-line platinum combination chemotherapy after first-line gefitinib
      treatment shows similar effects to first-line platinum combination chemotherapy
      in these patients remains unclear. Therefore, we here aimed to investigate the
      efficacy of platinum combination chemotherapy after first-line gefitinib
      treatment in NSCLC patients harboring sensitive EGFR mutations. METHODS/PATIENTS:
      We retrospectively evaluated the clinical effects of second-line platinum
      combination chemotherapy after first-line gefitinib treatment in NSCLC patients
      harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation)
      at five institutions. All patients were initially treated with gefitinib (250
      mg/day) followed by platinum combination chemotherapy as second-line
      chemotherapy. RESULTS: Between January 2006 and December 2012, 42 patients [8
      men, 34 women; median age, 63 years (range 39-75 years)] were enrolled. The
      overall response rate, disease control rate, and median progression-free survival
      (PFS) were 26.2, 61.9%, and 5.1 months, respectively, after the second-line
      treatment. The corresponding values for first-line gefitinib treatment were 69.0,
      95.2%, and 11.1 months, respectively. Moreover, second-line platinum combination
      chemotherapy with pemetrexed or bevacizumab-containing regimens was independently
      associated with improved PFS. CONCLUSIONS: Second-line platinum combination
      chemotherapy after first-line gefitinib treatment in NSCLC patients harboring
      sensitive EGFR mutations was effective and showed equivalent outcomes to first
      line platinum combination chemotherapy. After failure of first-line gefitinib
      therapy, second-line platinum combination chemotherapy with pemetrexed or
      bevacizumab might result in improved PFS.

PMID- 25990509
TI  - "Off-Label" Usage of Testicular Self-Examination (TSE): Benefits Beyond Cancer
      Detection.
AB  - Testicular cancer (TCa) is the most common cancer among 15- to 34-year-old males.
      Treatments are highly effective, which help foster approximately 98% 5-year
      survival rate. There are very few known causal factors of the disease (e.g.,
      cryptorchidism and family history), thus possibly limiting primary prevention
      methods. Secondary preventative measures, on the other hand, most notably
      testicular self-examination (TSE), are well-known and are promoted to help
      prevent late-stage diagnosis of TCa. However, debate ensues as to whether or not
      TSE provides any benefit. In light of a recent systematic review conducted by
      these authors assessing the effectiveness of TSE promotion interventions, we
      propose that the behavior can serve as a tool not just for detection of TCa, but
      other male-specific urogenital health concerns, including varicoceles,
      hydroceles, among others. Furthermore, we suggest that TSE can also help foster
      informed decision-making skills among males with regard to health concerns and
      treatment options. However, our advocacy is in direct conflict with U.S.
      Preventive Services Task Force's influential "D" rating of TSE and others who
      recommend against performing TSE. This article offers an overview of the dispute
      over TSE's purpose and net benefit. We conclude that TSE is a behavior that is
      beneficial beyond detecting cancer. These proposed "off-label" uses of the
      procedure make for an effectual means to promote testicular health, self
      awareness, and wellness among males. Recommendations for future research and
      advocacy are presented to the academy.

PMID- 25990510
TI  - Relationship Between Aerobic Fitness, the Serum IGF-1 Profiles of Healthy Young
      Adult African American Males, and Growth of Prostate Cancer Cells.
AB  - The growth of prostate tumors is mediated by the bioavailability of androgens and
      insulin-like growth factors. This study tested the hypothesis that healthy young
      adult African American men exhibiting low aerobic capacity (fitness) have serum
      insulin-like growth Factor-1 (IGF-1) and testosterone levels that promote growth
      of prostate cancer cells. A cross-sectional data research design was used to
      study groups of 18- to 26-year-old healthy men exhibiting low and moderate
      aerobic fitness, based on their peak oxygen consumption (VO2peak). The individual
      serum levels of IGF-1, IGF-1 binding protein-3 (IGFBP-3), and testosterone were
      measured. In vitro growth of androgen-dependent LNCaP prostate tumor cells was
      measured after incubation in culture medium fortified with each subject's serum.
      Aerobic capacity was significantly greater in the moderate-fitness group than in
      the low-fitness group without an intergroup difference in body mass index. The
      serum IGF-1 concentration was significantly higher in the low-fitness group in
      the absence of an intergroup difference in serum testosterone. The serum IGFBP-3
      concentration was significantly lower in the low-fitness group. Prostate tumor
      cell growth was significantly greater in the cultures incubated in media
      containing the sera of the low-fitness group than in the sera of the moderate
      fitness group. These findings suggest that moderate aerobic fitness in young
      adults may decrease the circulating levels of free IGF-1 and lower the potential
      to support growth of prostate cancer cells.

PMID- 25990511
TI  - Review: "Long-Term Medication Adherence in Acute Coronary Syndrome Survivors:
      Exploring Underlying Factors"--Corresponding Letter.

PMID- 25990512
TI  - Welfare of organic laying hens kept at different indoor stocking densities in a
      multi-tier aviary system. I: egg laying, and use of veranda and outdoor area.
AB  - Multi-tier aviary systems are becoming more common in organic egg production. The
      area on the tiers can be included in the net area available to the hens (also
      referred to as usable area) when calculating maximum indoor stocking densities in
      organic systems within the EU. In this article, results on egg production, laying
      behaviour and use of veranda and outdoor area are reported for organic laying
      hens housed in a multi-tier system with permanent access to a veranda and kept at
      stocking densities (D) of 6, 9 and 12 hens/m2 available floor area, with
      concomitant increases in the number of hens per trough, drinker, perch and nest
      space. In a fourth treatment, access to the top tier was blocked reducing
      vertical, trough and perch access at the lowest stocking density (treatment D6x).
      In all other aspects than stocking density, the experiment followed the EU
      regulations on the keeping of organic laying hens. Laying percentage was
      significantly lower (P<0.05) in D12 compared with the other stocking densities
      (90.6% v. 94.3% (+/- 0.7)), most likely due to the concomitant reduction in nest
      space and drinker availability per hen. No systematic effects of density were
      found on other laying variables (egg weight, eggs laid outside nests, aviary side
      preferences). Number of hens using the veranda increased with stocking density.
      Hens primarily used the range near the house (within 50 m) and hens kept at the
      lowest stocking density and the smallest group size appeared to use the outdoor
      area more extensively, based on an assessment of vegetation cover (P<0.05). For
      the measures reported here, the welfare consequences of increased stocking
      density were assessed to be minor; additional results are reported in the
      associated article (Steenfeldt and Nielsen, 2015).

PMID- 25990513
TI  - Validation of an a priori, index model of successful aging in a population-based
      cohort study: the successful aging index.
AB  - BACKGROUND: Many definitions of successful aging (SA) exist in the absence of an
      established consensus definition. There are few examples of a priori application
      of SA models in real world contexts using external validation procedures. The
      current study aims to establish the predictive validity of an a priori,
      continuous model of SA with respect to service utilization. METHODS: Individuals
      (n = 740; 64.2% female) aged 65 years and over (mean 75.9; SD 6.2), randomly
      selected from general practitioner registries in five sites across the United
      Kingdom included in the second and third combined screen and assessment waves of
      the Medical Research Council Cognitive Function and Aging Study (MRC CFAS; a
      longitudinal population-based cohort study) comprised the baseline and two-year
      follow-up in the current study. A Successful Aging Index (SAI) was created using
      items identified by systematic reviews of operational definitions and lay
      perspectives of SA, capturing physiological and psychosocial components.
      Demographic data and SAI components were collected at baseline. Outcome measures,
      i.e. health service use, informal care use, and functional service, were captured
      at two years follow-up. RESULTS: Logistic regression revealed significant
      relationships between the SAI and six of eight service use outcomes in models
      adjusted for age, sex, education, and socio-economic status. Analysis of the area
      under the receiver operating characteristic (ROC) curve demonstrated sufficient
      predictive capabilities for all models, (range 0.65-0.86). CONCLUSIONS: The SAI
      demonstrated a strong association, and predictive accuracy, with respect to
      service use, providing preliminary support for the practical utility and
      usefulness of this measure.

PMID- 25990514
TI  - Delisting of liver transplant candidates because of bacterial sepsis.

PMID- 25990515
TI  - A novel DNA sequence motif in human and mouse genomes.
AB  - We report a novel DNA sequence motif in human and mouse genomes. This motif has
      several interesting features indicating that it is highly likely to be an unknown
      functional sequence element. The motif is highly enriched in promoter regions.
      Locations of the motif sites in the genome have strong tendency to be clustered
      together. Motif sites are associated with increased phylogenetic conservation as
      well as elevated DNase I hypersensitivity (DHS) in ENCODE cell lines. Clustered
      motif sites are found in promoter regions of a substantial fraction of the
      protein-coding genes in the genome. All together, these indicate that the motif
      may have important functions associated with a large number of genes. 

PMID- 25990516
TI  - Development of Pgrac100-based expression vectors allowing high protein production
      levels in Bacillus subtilis and relatively low basal expression in Escherichia
      coli.
AB  - BACKGROUND: In general, fusion of recombinant genes to strong inducible promoters
      allowing intracellular expression in Bacillus subtilis is a two-step process. The
      ligation products are transformed into Escherichia coli, followed by
      identification of the correct plasmid, and this plasmid is subsequently
      transformed into B. subtilis. This raises the problem that basal level of
      expression of the recombinant gene could be harmful for E. coli cells. Based on
      the Pgrac promoter, we optimized the UP element, the -35, 15, -10 and the +1
      region to enhance the promoter activity in B. subtilis after induction. However,
      detailed investigations for a promoter to develop expression vectors that allows
      high protein production levels in B. subtilis and a relatively low basal
      expression levels in E. coli has not been studied yet. RESULTS: We screened the
      previously constructed library of E. coli - B. subtilis shuttle vectors for high
      level expression in B. subtilis and low basal level in E. coli. Promoter Pgrac100
      turned out to meet these criteria, in which beta-galactosidase expression level
      of Pgrac100-bgaB is about 9.2 times higher than Pgrac01-bgaB in B. subtilis and
      the ratio of those in induced B. subtilis over un-induced E. coli from Pgrac100
      bgaB is 1.3 times higher than Pgrac01-bgaB. Similarly, GFP expression level of
      Pgrac100-gfp is about 27 times higher than that of Pgrac01-gfp and the ratio from
      Pgrac100-gfp is 35.5 times higher than Pgrac01-gfp. This promoter was used as a
      basis for the construction of three novel vectors, pHT253 (His-tag-MCS), pHT254
      (MCS-His-tag) and pHT255 (MCS-Strep-tag). Expression of the reporter proteins
      BgaB and GFP using these expression vectors in B. subtilis at a low IPTG
      concentration were measured and the fusion proteins could be purified easily in a
      single step by using Strep-Tactin or IMAC-Ni columns. CONCLUSIONS: This paper
      describes the construction and analysis of an IPTG-inducible expression vector
      termed Pgrac100 for the high level production of intracellular recombinant
      proteins in B. subtilis and a relatively low basal expression level in E. coli.
      Based on this vector, the derivative vectors, Pgrac100-His-tag-MCS, Pgrac100-MCS
      His-tag and Pgrac100-MCS-Strep-tag have been constructed.

PMID- 25990518
TI  - Erratum.

PMID- 25990517
TI  - Endomyocardial biopsy findings in a patient with polymyositis-dermatomyositis.
AB  - Endomyocardial biopsy pathology in a patient with dermatomyositis cardiac
      involvement is reported. Clinical findings included acute heart failure and
      ischemic and conduction changes on electrocardiogram. Light microscopy showed
      focal myocyte necrosis without inflammation or fibrosis and prominent myocyte
      vacuolization. Electron microscopy confirmed the focal, acute myocyte necrosis
      and demonstrated nonspecific myocyte degeneration. Despite nonspecific
      morphologic findings, endomyocardial biopsy confirmed myocardial abnormalities
      associated with dermatomyositis and supported the use of aggressive
      antiinflammatory therapy, which resulted in a favorable clinical outcome. 

PMID- 25990519
TI  - Pathology of chronic cardiac rejection: An analysis of the epicardial and
      intramyocardial coronary arteries and myocardial alterations in 43 human
      allografts.
AB  - Forty-three cardiac allografts (39 autopsies and 4 surgically resected hearts)
      showing chronic rejection-defined as greater than 75% narrowing of one or more
      major coronary arteries (MCA) with or without severe narrowing of intramyocardial
      coronary arteries (ICA)-were studied histologically. MCA showed purely concentric
      narrowing in 24 patients (56%), and 19 patients (44%) showed eccentric narrowing
      in some arteries. Fibrofatty (collipid) plaques were seen in 54%, abundant foam
      cells sans free lipid in 33%, purely fibrous plaques in 14%, and calcification in
      9%. Four pathologic alterations separated graft atherosclerosis from usual
      atherosclerosis: (i) the presence in the MCA and/or ICA of either active or
      healed vasculitis, (ii) outer medial defects attributable to mediolysis and/or
      foam cell transformation in the MCA, (iii) the diffuse nature of the
      atherosclerotic-like changes, and (iv) obliterative narrowing of the ICA. No
      difference was found between early and late survivors with regard to features of
      graft atherosclerosis. The majority of the patients studied had received steroid
      based immunosuppression. MCA and/or ICA active vasculitis was observed in the
      absence of acute myocardial rejection in some patients. ICA showed intimal
      thickening in 37% of patients, active vasculitis in 21%, healed vasculitis in 7%,
      and combination of the latter two changes in 12%. Acute myocardial ischemia,
      present in 33 hearts (77%), had the following distribution: subendocardial in
      42%, focal in 36%, and regional transmural in 21%. Myocytolysis (83%),
      coagulative necrosis (26%), and contraction band necrosis (16%) were noted.
      Replacement fibrosis of the myocardium was frequently observed (44%), followed by
      interstitial (33%) and perivascular fibrosis (1%). Patients with chronic
      rejection showed no difference with regard to the incidence and severity of
      rejection episodes during life compared with patients without chronic rejection. 

PMID- 25990520
TI  - Vascular rejection in cardiac transplantation: Histologic, immunopathologic, and
      ultrastructural features.
AB  - Although the majority of rejection found in cardiac transplant biopsies is
      cellular in type, a variety of vascular alterations occur in cardiac biopsies,
      constituting different forms of rejection that can be recognized using light
      microscopic and immunopathologic criteria. In this report, pathologic aspects of
      the vascular alterations associated with vascular and mixed rejection of cardiac
      allografts are described in detail. Methods and controls used in this report are
      identical to those previously reported. The histologic, immunopathologic, and
      ultrastructural findings associated with vascular rejection and other vascular
      processes in cardiac allografts are discussed. The relationship of these findings
      to chronic allograft rejection and potential pathogenetic mechanisms of these
      vascular changes are also detailed. 

PMID- 25990521
TI  - Anomalous origin of the left coronary artery from the nonfacing aortic sinus: A
      study in the Syrian hamster.
AB  - A coronary artery that arises from the nonfacing (posterior or dorsal) aortic
      sinus is regarded as having an anomalous origin. We studied 34 Syrian hamsters in
      which the left coronary artery originated from the nonfacing aortic sinus. All
      hamsters belonged to a single family subjected to high endogamous pressure in our
      laboratory. Twenty-four specimens were examined using a corrosion-cast technique
      and scanning electron microscopy, whereas the remaining 10 were studied
      histologically. The aortic valve was normal in 15 cases, whereas it was bicuspid
      in the other 19 cases. In each specimen of our series, the left coronary artery
      arose with an acute angle with respect to the aortic valve. Moreover, when the
      coronary ostium was located in the center of the nonfacing aortic sinus, the
      proximal coronary artery had an intramural aortic course. These left coronary
      artery arrangements might underlie an unfavorable coronary circulation
      physiology. Our morphologic findings agree with the morphogenetic hypothesis that
      each aortic sinus has the potential to develop coronary artery buds, which hollow
      out from the aorta to become coronary artery trunks. 

PMID- 25990522
TI  - Histological features of a polymer endovascular prosthesis after transcatheter
      implantation in porcine arteries.
AB  - A novel approach for the treatment of acute complications and the prevention of
      restenosis after percutaneous transluminal angioplasty may be the placement of
      endovascular prostheses (stents). Stents constructed of metal have proven to be
      thrombogenic, and although they show a tendency to reduce restenosis, they do not
      prevent it. Pursuant to the search for stents with improved material and surface
      characteristics, we report in this paper the histological results obtained with a
      synthetic polymer (polyethylene terephthalate) stent after placement in porcine
      peripheral arteries. Eight stents were placed at a preselected site and resulted
      in a 87.5% angiographic patency rate at four weeks' follow-up examination. The
      neointima measured 114 +/- 38 MUm (mean +/- SEM) on top of the fibers and 246 +/-
      44 MUm between the fibers. Medial impression by the stent measured 27% +/- 5%.
      The neointima consisted mainly of smooth muscle cells. A variable inflammatory
      reaction and foreign body response to the polymer was observed in all vessels.
      The present study shows the feasibility of the arterial implantation of polymer
      stents, in that they result in good intermediate-term arterial patency and
      limited neointimal hyperplasia. The observed inflammatory reaction, if prolonged,
      may limit the use of this polymer stent. 

PMID- 25990523
TI  - Lipid accumulation in the subendothelial cells of human aortic intima impairs
      cell-to-cell contacts: A comparative study in situ and in vitro.
AB  - We have modified our technique used to examine the three-dimensional
      cytoarchitecture of human aorta. Using this modification we confirmed the
      disruption of the contacts among subendothelial cells in the fatty streaks.
      Thinning and arborization of contact-forming cellular processes were also
      demonstrated. The incubation of cultured human aortic subendothelial cells with
      desialylated low-density lipoproteins (LDL), LDL immobilized on latex, and LDL
      free latex microspheres induced the alterations in cell-to-cell contacts similar
      to those occurring in a fatty streak in situ. It is proposed that these
      alterations may be associated with lipid accumulation and activation of
      phagocytosis and/or intracellular accumulation of large insoluble particles. 

PMID- 25990524
TI  - Immunohistochemical detection of very recent myocardial infarctions in humans
      with antibodies against heart-type fatty acid-binding protein.
AB  - Depletion of human heart-type fatty acid-binding protein (H-FABP) from
      cardiomyocytes in infarcted areas with varying postinfarction intervals was
      studied in 25 autopsy cases. In 23 autopsy cases myocardial infarction was the
      clinical diagnosis; 2 cases were noncardiac deaths and served as controls.
      Formaldehyde-fixed and paraffin-embedded myocardial tissue sections were stained
      immunohistochemically with antibodies to human H-FABP. H-FABP immunohistochemical
      findings were compared with those from conventional nitroblue tetrazolium (NBT)
      macroenzyme staining and conventional histochemical hematoxylin-eosin staining of
      sections of the same infarctions. In all cases of infarction confirmed by NBT
      staining, decreased or absent H-FABP immunostaining was observed. In 12 cases of
      clinically diagnosed infarction, H-FABP depletion could be demonstrated in areas
      that showed normal NBT staining. These findings strongly suggest that
      immunohistochemical staining with antibodies to H-FABP can confirm the clinical
      diagnosis or suspicion of early myocardial infarction. In both control cases no
      depletion of H-FABP was observed in cardiomyocytes in different myocardial tissue
      sections, and macroenzyme staining with NBT was normal. We conclude that H-FABP
      immunostaining may detect very recent ischemia/ infarction in human myocardium
      and can be applied in routine autopsy pathology. 

PMID- 25990525
TI  - Histopathology of the heart in tetanus.
AB  - Despite modern intensive care, the mortality rate for systemic tetanus
      intoxication remains high. The prevention of deaths attributable to respiratory
      muscle spasm has made apparent a clinical syndrome of cardiovascular instability
      characterized by labile blood pressure and heart rate and associated elevated
      plasma catecholamine levels. A 60-year-old man treated at our hospital
      demonstrated this clinical problem and was shown by echocardiography to have a
      left ventricular ejection fraction of only 8%. Electrocardiographic abnormalities
      and elevated creatine phosphokinase were further evidence of myocardial damage.
      At autopsy, the 430-g heart showed mild concentric left ventricular hypertrophy
      and minimal coronary atherosclerosis. Microscopically there were interstitial
      edema, collections of Anitschkow cells, and a diffuse lymphohistiocytic
      infiltrate with rare plasma cells and granulocytes. Review of all cases of
      tetanus recorded at the Dade County Medical Examiner's Office since 1955 was
      undertaken. Of 52 cases, 23 had hematoxylin-eosin-stained glass slides of heart
      sections; for 10 of these, paraffin blocks were also available. Histopathologic
      features of cardiac injury included interstitial edema, increased cellularity of
      the interstitium (lymphocytes, histiocytes, Anitschkow cells, and rare plasma
      cells and granulocytes), intracellular edema, sarcoplasmic hypereosinophilia, and
      paradiscal contraction bands. Immunoperoxidase stains revealed that the majority
      of the lymphocytes in these hearts were T cells. Hypotheses as to the etiology
      and pathogenesis of these cardiac changes are reviewed. 

PMID- 25990526
TI  - Myocardial damage induced by tropical rattlesnake (Crotalus durissus terrificus)
      venom in rats.
AB  - This article describes the light and electron microscopic appearance of the rat
      myocardium at various time intervals after the administration of Crotalus
      durissus terrificus venom by intraperitoneal route. The crotalid envenomation
      produced small foci of myocardial necrosis scattered throughout the base of the
      ventricles. These lesions were predominantly perivascular and were associated
      with slight to moderate interstitial edema as well as infiltration of mononuclear
      cells and of a great number of mast cells. The first changes appeared 24 hours
      after envenomation and reached maximal severity after 4 days. By 8 days, the
      cardiac morphology was comparable to that of control animals except for small
      foci of interstitial fibrosis at the base of both ventricles-probably
      attributable to reabsorption of necrotic myofibers and healing-and a small number
      of degenerated myofibers. The main points concerning these findings are their
      preferential localization at the base of the heart and the association of the
      foci of myocytolytic necrosis with a large number of mast cells. On the basis of
      these data, although nonspecific, the mechanism of venom-induced myocardial
      damage is discussed. Moreover, these findings call attention to the potential
      cardiotoxic effect of crotalid poisoning in humans. 

PMID- 25990527
TI  - Angiosarcoma of the heart predominantly involving the pericardium: A
      clinicopathologic study with electron-microscopic and immunohistochemical
      correlation.
AB  - A case of angiosarcoma of the heart with predominant involvement of the
      pericardium and diffuse bilateral lymphangitic spread to both lungs is presented.
      The patient was a 32-year-old man admitted for cough, dyspnea, and intermittent
      hemoptysis. Chest x-ray and computed tomography scans revealed bilateral
      pulmonary infiltrates and pericardial effusion. An echocardiogram showed a large
      oval mass overlying and compressing the right atrium and ventricle. At autopsy,
      multiple hemorrhagic tumor nodules were present in the pericardial sac, and an 8
      cm hemorrhagic tumor mass was found overlying and compressing the right atrial
      appendage and infiltrating the heart muscle. Histological, immunohistochemical,
      and electron-microscopic examination revealed the features of angiosarcoma. The
      predominant pericardial location observed in this case was a source of difficulty
      both in the clinical and pathological differential diagnosis and raised the
      question of possible primary pericardial angiosarcoma with secondary involvement
      of the heart. A review of the literature on this topic is presented. 

PMID- 25990528
TI  - In vivo diagnosis of cardiac angiosarcoma by endomyocardial biopsy.
AB  - The present-day diagnosis of primary heart tumors is achieved by cardiac imaging
      and confirmed by morphological examination after surgical resection. We describe
      the case of a 36-year-old man with a right atrioventricular mass in whom
      angiosarcoma was diagnosed by transvenous endomyocardial biopsy. Surgery was not
      attempted because of pulmonary metastases, and the patient died 12 months later.
      This experience indicates that precise in vivo histological diagnosis of
      malignant primary cardiac tumor is possible without thoracotomy. 

PMID- 25990529
TI  - The Gamna-Gandy body in cardiac myxoma.
AB  - The so-called Gamna-Gandy body is a sclerosiderotic granulomatous lesion composed
      of degenerate collagen fibers encrusted with iron and calcium. Only five cases of
      Gamna-Gandy body in the heart have been documented. We studied 7 patients with
      cardiac myxoma who underwent surgery in our university hospital, and Gamna-Gandy
      body was present in 3. All the Gamna-Gandy body-positive patients had ingested
      anticoagulant agents and/or antiplatelet drugs. These results suggest that the
      Gamna-Gandy body in cardiac myxoma is not a rare pathologic condition and that
      anticoagulant and/or antiplatelet therapy may have a causal relation to the
      pathogenesis of this lesion. 

PMID- 25990530
TI  - Gamna-Gandy body of the heart: Petrified cardiac myxoma mimicking atrial
      thrombus.

PMID- 25990531
TI  - Estimation of incidence, prevalence, and age-at-diagnosis of myasthenia gravis
      among adults by hospital discharge records.
AB  - BACKGROUND: The Hungarian Health Insurance Fund, using appropriate information
      technology, covers all of the secondary care of the country and maintains a
      database of Hospital Discharge Records (HDR). Our study aimed to determine the
      incidence, average age-at-diagnosis (AaD), and prevalence of myasthenia gravis
      (MG) among adults and the regional heterogeneity of these measures to assess the
      potential usefulness of HDRs for monitoring. METHODS: The nationwide database of
      336,679 HDRs from 2004 to 2009 was analyzed. The incidence and prevalence were
      determined for adults in 2007. Patients with MG code in 2007, 2008, and 2009 but
      without that in 2004-2006 were defined as incident. Distribution of AaD was
      described for these cases. Patients with an MG code in 2007, 2008, and 2009 were
      defined as prevalent in 2007. The heterogeneity of regional age-standardized
      indices was tested. RESULTS: The observed incidence and prevalence was
      2.76/100,000 (men: 2.37/100,000; women: 3.11/100,000) and 17.42/100,000 (male:
      13.08/100,000; female: 21.28/100,000), respectively. These estimates were within
      published ranges. The mean AaD was significantly higher for men than for women
      (63.60 vs. 51.92; p < 0.001). Significant regional heterogeneity was observed for
      all measures. CONCLUSIONS: HDRs seem to be useful for developing MG indicators
      because they adequately estimate epidemiological parameters of MG occurrence.

PMID- 25990532
TI  - [Researcher of the month].

PMID- 25990533
TI  - Fasciola hepatica from naturally infected sheep and cattle in Great Britain are
      diploid.
AB  - Diploid (2n = 2x = 20) and triploid (2n = 3x = 30) Fasciola hepatica have been
      reported in the UK, and in Asia diploid, triploid and mixoploid (2x/3x) Fasciola
      spp. exist but there is little information to indicate how common triploidy is,
      particularly in UK fluke. Here the ploidy of 565 adult F. hepatica from 66
      naturally infected British sheep and 150 adult F. hepatica from 35 naturally
      infected British cattle was determined. All 715 of these parasites were diploid,
      based on observation of 10 bivalent chromosomes and sperm (n = 335) or, since
      triploids are aspermic, sperm alone (n = 380). This constitutes the first
      extensive analysis of the ploidy of F. hepatica field isolates from Great Britain
      and shows that most F. hepatica isolated from cattle and sheep are diploid and
      have the capacity to sexually reproduce. These data suggest that triploidy, and
      by extension parthenogenesis, is rare or non-existent in wild British F. hepatica
      populations. Given that F. hepatica is the only species of Fasciola present in
      Britain our results indicate that the parasite is predominantly diploid in areas
      where F. hepatica exists in isolation and suggests that triploidy may only
      originate in natural populations where co-infection of F. hepatica and its sister
      species Fasciola gigantica commonly occurs. 

PMID- 25990534
TI  - Biomechanical Evaluation of Plate Versus Lag Screw Only Fixation of Distal Fibula
      Fractures.
AB  - Traditional fixation of unstable Orthopaedic Trauma Association type B/C ankle
      fractures consists of a lag screw and a lateral or posterolateral neutralization
      plate. Several studies have demonstrated the clinical success of lag screw only
      fixation; however, to date no biomechanical comparison of the different
      constructs has been performed. The purpose of the present study was to evaluate
      the biomechanical strength of these different constructs. Osteotomies were
      created in 40 Sawbones((r)) distal fibulas and reduced using 1 bicortical 3.5-mm
      stainless steel lag screw, 2 bicortical 3.5-mm lag screws, 3 bicortical 3.5-mm
      lag screws, or a single 3.5-mm lag screw coupled with a stainless steel
      neutralization plate with 3 proximal cortical and 3 distal cancellous screws. The
      constructs were tested to determine the stiffness in lateral bending and rotation
      and failure torque. No significant differences in lateral bending or rotational
      stiffness were detected between the osteotomies fixed with 3 lag screws and a
      plate. Constructs fixed with 1 lag screw were weaker for both lateral bending and
      rotational stiffness. Osteotomies fixed with 2 lag screws were weaker in lateral
      bending only. No significant differences were found in the failure torque.
      Compared with lag screw only fixation, plate fixation requires larger incisions
      and increased costs and is more likely to require follow-up surgery. Despite the
      published clinical success of treating simple Orthopaedic Trauma Association B/C
      fractures with lag screw only fixation, many surgeons still have concerns about
      stability. For noncomminuted, long oblique distal fibula fractures, lag screw
      only fixation techniques offer construct stiffness similar to that of traditional
      plate and lag screw fixation. 

PMID- 25990535
TI  - Tarsal Coalitions: Preliminary Results After Operative Excision and Silicone
      Sheet Interposition in Children.
AB  - Symptomatic tarsal coalitions that begin in early adolescence are usually treated
      by resection and interposition (fat, muscle, or bone wax) to prevent recurrence.
      The purpose of the present retrospective study was to describe our operative
      technique and report our clinical and radiologic outcomes with sterile silicone
      sheet interposition after resection of painful tarsal coalitions in 4 children (4
      feet). The present series included 1 case of talocalcaneal synchondrosis and 3 of
      synostosis (2 talocalcaneal and 1 cuboid-navicular). Two validated functional
      scales were used to assess the patients' overall outcome and satisfaction with
      the procedure: the American Orthopaedic Foot and Ankle Society ankle-hindfoot
      score and the Foot Function Index. Conventional radiography, computed tomography
      with 3-dimensional reconstruction, and magnetic resonance imaging were performed
      at the final follow-up visit. The mean follow-up period was 40 (range 12 to 80)
      months. The mean age at surgery was 10.5 (range 8 to 13) years. All patients had
      achieved their desired activity level at 6 months postoperatively. The mean
      American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 93.5 (range
      74 to 100), and the mean Foot Function Index was 3.25% (range 0% to 13%). No
      recurrence of the coalition on imaging at the final follow-up visit was observed
      in this patient series. Sterile silicone sheet interposition can be used to
      prevent recurrence of tarsal coalition in symptomatic tarsal coalitions after
      failure of conservative management.

PMID- 25990536
TI  - How to define bifurcation lesion complexity and how to successfully perform
      percutaneous treatment.
AB  - Historically, percutaneous coronary interventions (PCI) of bifurcation lesions
      have been associated with a lower procedural success rate, a higher complication
      rate, and less favorable clinical outcomes, compared to PCI of non-bifurcation
      lesions. However, percutaneous treatment of coronary bifurcation lesions have
      been improved over the past decade due to improvements in stent design and the
      introduction of specific bifurcation stent techniques. Some even argue that PCI
      of bifurcation lesions should no longer be considered as being complex. However,
      recent studies have shown that there are still certain bifurcation lesion
      subtypes which are at higher risk for adverse cardiac events after PCI. Future
      efforts, including the development of a dedicated bifurcation device, should be
      focused on this specific high-risk subgroup, including distal left main
      bifurcations. 

PMID- 25990537
TI  - Identification of genes containing expanded purine repeats in the human genome
      and their apparent protective role against cancer.
AB  - Purine repeat sequences present in a gene are unique as they have high propensity
      to form unusual DNA-triple helix structures. Friedreich's ataxia is the only
      human disease that is well known to be associated with DNA-triplexes formed by
      purine repeats. The purpose of this study was to recognize the expanded purine
      repeats (EPRs) in human genome and find their correlation with cancer
      pathogenesis. We developed "PuRepeatFinder.pl" algorithm to identify non
      overlapping EPRs without pyrimidine interruptions in the human genome and
      customized for searching repeat lengths, n >= 200. A total of 1158 EPRs were
      identified in the genome which followed Wakeby distribution. Two hundred and
      ninety-six EPRs were found in geneic regions of 282 genes (EPR-genes). Gene
      clustering of EPR-genes was done based on their cellular function and a large
      number of EPR-genes were found to be enzymes/enzyme modulators. Meta-analysis of
      282 EPR-genes identified only 63 EPR-genes in association with cancer, mostly in
      breast, lung, and blood cancers. Protein-protein interaction network analysis of
      all 282 EPR-genes identified proteins including those in cadherins and VEGF. The
      two observations, that EPRs can induce mutations under malignant conditions and
      that identification of some EPR-gene products in vital cell signaling-mediated
      pathways, together suggest the crucial role of EPRs in carcinogenesis. The new
      link between EPR-genes and their functionally interacting proteins throws a new
      dimension in the present understanding of cancer pathogenesis and can help in
      planning therapeutic strategies. Validation of present results using techniques
      like NGS is required to establish the role of the EPR genes in cancer pathology. 

PMID- 25990539
TI  - Hope and Abstinence Self-Efficacy: Positive Predictors of Negative Affect in
      Substance Abuse Recovery.
AB  - Goal-oriented thinking, including hope and self-efficacy, might play a
      constructive and integral role in the substance abuse recovery process, although
      such an effect may differ by race. The current study investigated hope and self
      efficacy, specifically abstinence self-efficacy, as predictors of negative affect
      (i.e. depression and anxiety) in a longitudinal sample of men and women in
      substance abuse recovery who lived in sober living homes. We found hope agency
      and self-efficacy were related but not identical constructs; hope agency and self
      efficacy predicted depressive and anxiety symptoms for individuals in recovery,
      yet these relationships were moderated by race. Theoretical and clinical
      implications for promoting positive affect among individuals in substance abuse
      recovery are discussed. 

PMID- 25990540
TI  - Religious beliefs, practices, and health in colorectal cancer patients in Saudi
      Arabia.
AB  - OBJECTIVE: Colorectal cancer (CRC) patients experience considerable psychological
      stress because of changes brought on by their illness. Religion may be a resource
      for such patients. We examined the prevalence of religious beliefs and practices
      in CRC patients and correlation with demographic, social, psychological, and
      physical health characteristics. METHODS: Seventy CRC patients (all Muslim) in
      Jeddah, Saudi Arabia, were surveyed using a 13-item Muslim religiosity scale.
      Standard measures were used to assess depressive symptoms, depressive disorder,
      and social support; demographic and social factors, psychiatric history, and
      disease factors were also measured. RESULTS: All 70 participants (100%) engaged
      in group worship and prayer (Fard) five times/day, and 75.7% never skipped or
      combined two or more obligatory prayers; 71.4% read or recited the Qur'an several
      times/week or daily; 80.0% gave money to the poor each year (Zakat); 71.4% fasted
      throughout the month of Ramadan (Sawm) and other times as well; 91.4% said they
      'definitely' experienced the presence of Allah; and 74.3% said their entire
      approach to life was definitely based on their religious beliefs. Overall
      religiosity was inversely related to depressive symptoms (B = -0.58, SE = 0.30, p
      = 0.026) and suicidal ideation (B = -0.07, SE = 0.03, p = 0.025), after
      controlling for financial status and social factors. CONCLUSIONS: Religious
      involvement was widespread in this sample of CRC patients in Saudi Arabia and was
      related to fewer depressive symptoms and less suicidal ideation. No relationship
      was found with stage of disease or duration of treatment.

PMID- 25990541
TI  - Functionalisation and immobilisation of an Au(110) surface via uracil and 2
      thiouracil anchored layer.
AB  - We study surface functionalisation by uracil and 2-thiouracil, and immobilisation
      of several DNA moieties on functionalised gold surfaces. The combination of X-ray
      photoelectron and near-edge X-ray absorption spectroscopy allowed us to obtain a
      complete understanding of complex interfacial processes, starting from adsorption
      of biomolecules onto the metallic surface and progressing towards a specific
      surface functionality for interactions with other biologically related
      adsorbates. Au(110) surfaces were functionalised by deposition of uracil and 2
      thiouracil molecules under vacuum conditions, and then tested for their
      selectivity by immobilisation of different DNA moieties deposited from aqueous
      solutions. We observed that adenine, adenosine, and RNA polymer (polyadenylic
      acid) from saturated solutions were immobilized successfully on the 2-thiouracil,
      but those from dilute (1%) solutions were not. However, cytosine failed to adsorb
      even from saturated solution. The chemical states of the biologically related
      adsorbates were investigated and the geometrical orientation of uracil and 2
      thiouracil on the Au(110) surface was determined using both spectroscopic
      techniques. 

PMID- 25990544
TI  - Multiattribute health utility scoring for the computerized adaptive measure CAT
      5D-QOL was developed and validated.
AB  - OBJECTIVES: The CAT-5D-QOL is a previously reported item response theory (IRT)
      based computerized adaptive tool to measure five domains (attributes) of health
      related quality of life. The objective of this study was to develop and validate
      a multiattribute health utility (MAHU) scoring method for this instrument. STUDY
      DESIGN AND SETTING: The MAHU scoring system was developed in two stages. In phase
      I, we obtained standard gamble (SG) utilities for 75 hypothetical health states
      in which only one domain varied (15 states per domain). In phase II, we obtained
      SG utilities for 256 multiattribute states. We fit a multiplicative regression
      model to predict SG utilities from the five IRT domain scores. The prediction
      model was constrained using data from phase I. We validated MAHU scores by
      comparing them with the Health Utilities Index Mark 3 (HUI3) and directly
      measured utilities and by assessing between-group discrimination. RESULTS: MAHU
      scores have a theoretical range from -0.842 to 1. In the validation study, the
      scores were, on average, higher than HUI3 utilities and lower than directly
      measured SG utilities. MAHU scores correlated strongly with the HUI3 (Spearman
      rho = 0.78) and discriminated well between groups expected to differ in health
      status. CONCLUSION: Results reported here provide initial evidence supporting the
      validity of the MAHU scoring system for the CAT-5D-QOL.

PMID- 25990542
TI  - Genome methylation patterns in male breast cancer - Identification of an epitype
      with hypermethylation of polycomb target genes.
AB  - Male breast cancer (MBC) is a rare disease that shares both similarities and
      differences with female breast cancer (FBC). The aim of this study was to assess
      genome-wide DNA methylation profiles in MBC and compare them with the previously
      identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the
      intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC
      and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC
      tumors revealed two stable epitypes, designated ME1 and ME2. The methylation
      patterns differed significantly between the groups and were closely associated
      with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group
      were more proliferative and aggressive than ME2 tumors, and showed a tendency
      toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2
      target genes and high expression of EZH2, one of the core components of PRC2.
      Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B
      FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster.
      The majority of the MBC tumors remained grouped together within the clusters
      rather than being interspersed among the FBC tumors. Differences in the genomic
      location of methylated CpGs, as well as in the regulation of central canonical
      pathways may explain the separation between MBC and FBC tumors in the respective
      clusters. These findings further suggest that MBC is not readily defined using
      conventional criteria applied to FBC. 

PMID- 25990538
TI  - Protein kinase CK2 in breast cancer: the CK2beta regulatory subunit takes center
      stage in epithelial plasticity.
AB  - Structurally, protein kinase CK2 consists of two catalytic subunits (alpha and
      alpha') and two regulatory subunits (beta), which play a critical role in
      targeting specific CK2 substrates. Compelling evidence shows the complexity of
      the CK2 cellular signaling network and supports the view that this enzyme is a
      key component of regulatory protein kinase networks that are involved in several
      aspects of cancer. CK2 both activates and suppresses the expression of a number
      of essential oncogenes and tumor suppressors, and its expression and activity are
      upregulated in blood tumors and virtually all solid tumors. The prognostic
      significance of CK2alpha expression in association with various
      clinicopathological parameters highlighted this kinase as an adverse prognostic
      marker in breast cancer. In addition, several recent studies reported its
      implication in the regulation of the epithelial-to-mesenchymal transition (EMT),
      an early step in cancer invasion and metastasis. In this review, we briefly
      overview the contribution of CK2 to several aspects of cancer and discuss how in
      mammary epithelial cells, the expression of its CK2beta regulatory subunit plays
      a critical role in maintaining an epithelial phenotype through CK2-mediated
      control of key EMT-related transcription factors. Importantly, decreased CK2beta
      expression in breast tumors is correlated with inefficient phosphorylation and
      nuclear translocation of Snail1 and Foxc2, ultimately leading to EMT induction.
      This review highlights the pivotal role played by CK2beta in the mammary
      epithelial phenotype and discusses how a modest alteration in its expression may
      be sufficient to induce dramatic effects facilitating the early steps in tumor
      cell dissemination through the coordinated regulation of two key transcription
      factors. 

PMID- 25990545
TI  - Surgical Treatment of Insertional Achilles Tendinopathy With or Without Flexor
      Hallucis Longus Tendon Transfer: A Prospective, Randomized Study.
AB  - BACKGROUND: Chronic insertional Achilles tendinopathy is a common pathology that
      can be difficult to manage. Some experts have advocated augmentation with the
      flexor hallucis longus (FHL) tendon in patients over age 50 and those with more
      severe tendon disease. We hypothesized that FHL augmentation would be associated
      with superior clinical outcome scores and greater ankle plantar flexion strength
      compared with Achilles debridement alone. METHODS: Consecutive patients older
      than 50 years who had failed nonoperative treatment for chronic insertional
      Achilles tendinopathy were randomly assigned to Achilles decompression and
      debridement alone (control group) or Achilles decompression and debridement
      augmented with FHL transfer (FHL group). Outcome measures included American
      Orthopaedic Foot & Ankle Society (AOFAS) ankle/hindfoot score, visual analog
      scale (VAS) for pain, ankle and hallux plantar flexion strength, and a patient
      satisfaction survey. A total of 39 enrolled patients had a minimum 1-year follow
      up, 18 in the control group and 21 in the FHL transfer group. The average patient
      age was 60.5 years. RESULTS: AOFAS and VAS scores improved in both groups at 6
      months and 1 year with no difference between groups. There was greater ankle
      plantar flexion strength in the FHL group at 6 months and at 1 year compared with
      the control group (P < .05). There was no difference between the 2 groups in
      hallux plantar flexion strength preoperatively and at 1 year after surgery. Some
      87% of patients were satisfied with the outcome of their procedure. There was no
      significant increase in wound complications in the FHL group (P < .05).
      CONCLUSION: We found no differences in pain, functional outcome (as measured by
      the AOFAS ankle/hindfoot scale), and patient satisfaction when comparing patients
      treated with Achilles debridement alone versus FHL augmentation for chronic
      Achilles tendinopathy. Ankle plantar flexion strength appeared to be improved
      with FHL transfer, with no loss of hallux plantar flexion strength. Although FHL
      transfer was a safe adjunct to tendon debridement and partial ostectomy for
      insertional Achilles tendinopathy in older patients with little compromise in
      function, it may not be necessary for primary cases. LEVEL OF EVIDENCE: Level 1,
      prospective randomized trial.

PMID- 25990547
TI  - Evaluation outcomes of a long-running adult nutrition education programme.
AB  - OBJECTIVE: For more than 20 years, the FOODcents adult nutrition education
      programme has been delivered to Western Australians. The aim of the programme is
      to provide disadvantaged individuals with the knowledge, skills and motivation to
      buy healthy foods on a limited budget. The present study evaluated whether the
      FOODcents curriculum and the way it is delivered are effective in improving
      participants' nutrition-related knowledge and behaviours. DESIGN: Evaluation data
      were collected via in-session pre-post questionnaires and a post-course online
      questionnaire. SETTING: Western Australia. SUBJECTS: Data were collected from
      participants attending just over one-half (54 %) of the FOODcents courses
      conducted over the two-year evaluation period. In total, 927 course participants
      provided usable data. RESULTS: After exposure to the course, respondents
      demonstrated an improved ability to: (i) categorize foods according to the
      frequency with which they should be consumed and the proportion of the food
      budget that should be allocated to them; (ii) correctly interpret nutrition
      labels on food products; and (iii) appreciate the link between diet/obesity and a
      range of diseases. Improvements in the latter were especially pronounced among
      participants of low socio-economic status. In terms of behaviour change,
      significant improvements in fruit and vegetable consumption were reported, along
      with reductions in the consumption of fast food. Participants of low socio
      economic status reported the greatest changes. CONCLUSIONS: The results indicate
      that the FOODcents nutrition education programme improves participants' nutrition
      related knowledge and behaviours.

PMID- 25990548
TI  - Diagnosis of Chikungunya dominated co-infection with dengue during an outbreak in
      south India (2010 and 2012).
AB  - Following a report of dengue outbreak from January 2010 to 2012 in the
      Tirunelveli, Theni, Dharmapuri and Thiruvallur districts of Tamil Nadu state,
      India, an investigation was carried out. The study was to demonstrate the
      probable presence of Chikungunya viral antibodies in patients clinically
      suspected of dengue fever. Out of 331 samples analysed, dengue viral antibodies
      were observed in 14.8% (n = 49) of patients, while 16.6% (n = 55) were positive
      for Chikungunya viral specific IgM antibodies. In the four districts surveyed,
      patients found positive for Chikungunya were found to be higher than dengue. The
      clinician should consider Chikungunya in the differential diagnosis of dengue
      like infection appearing in the community.

PMID- 25990550
TI  - DNA methylation and epigenomics: new technologies and emerging concepts.
AB  - A report of the Keystone Symposia joint meetings on DNA Methylation and
      Epigenomics held in Keystone, Colorado, USA, 29 March to 3 April, 2015. 

PMID- 25990549
TI  - Integration of Pulse Trains in Humans and Guinea Pigs with Cochlear Implants.
AB  - Temporal integration (TI; threshold versus stimulus duration) functions and
      multipulse integration (MPI; threshold versus pulse rate) functions were measured
      behaviorally in guinea pigs and humans with cochlear implants. Thresholds
      decreased with stimulus duration at a fixed pulse rate and with pulse rate at a
      fixed stimulus duration. The rates of threshold decrease (slopes) of the TI and
      MPI functions were not statistically different between the guinea pig and human
      subject groups. A characteristic of the integration functions that the two groups
      shared was that the slopes of the TI functions were similar in magnitude to
      slopes of the MPI function only at low pulse rates (< approximately 300 pulses
      per second). This is consistent with the notion that the TI functions and the MPI
      functions at the low rates are mediated by a mechanism of long-term integration
      described in the statistical "multiple looks" model. Histological analysis of the
      guinea pig cochleae suggested that the slopes of both the MPI and the TI
      functions were dependent on sensory and neural health near the stimulated
      regions. The strongest predictor for spiral ganglion cell densities measured near
      the stimulation sites was the slope of the MPI functions below 1,000 pps. Several
      mechanisms may be considered to account for the association of shallow
      integration functions with poor sensory and neural status. These mechanisms are
      related to abnormal across-fiber synchronization, increased refractoriness and
      adaptation with impaired neural function, and steep growth of neural excitation
      with current level associated with neural pathology. The slope of the integration
      functions can potentially be used as a non-invasive measure for identifying
      stimulation sites with poor neural health and selecting those sites for removal
      or rehabilitation, but these applications remain to be tested. 

PMID- 25990551
TI  - Is it time for a rethink of the management of patients with rectal cancer?

PMID- 25990552
TI  - Drug combination that corrects deficient protein in cystic fibrosis improves lung
      function.

PMID- 25990553
TI  - Incidence trends of lung cancer by immigration status among Chinese Americans.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related death among
      Chinese Americans. A detailed examination of incidence trends by immigration
      status and histology may inform the etiology of lung cancer in this growing
      population. METHODS: California Cancer Registry data were enhanced with data on
      patient nativity. Lung cancer incidence rates for Chinese males and females were
      computed for the years 1990-2010, and rates by immigration status and histology
      were computed for 1990-2004. Trends were assessed with annual percentage change
      (APC) statistics (two-sided P values) based on linear regression. RESULTS: A
      total of 8,167 lung cancers were diagnosed among California Chinese from 1990 to
      2010. Overall incidence increased nonstatistically among U.S.-born males (APC,
      2.1; 95% CI, -4.9 to 9.7), but decreased significantly among foreign-born (APC, 
      1.7; 95% CI, -2.9 to -0.6). Statistically significant decreasing trends were
      observed for non-small cell lung cancer (NSCLC), specifically the squamous cell
      and large cell carcinoma subtypes among foreign-born males. Among females,
      incidence decreased nonsignificantly among U.S.-born (APC, -2.8; 95% CI, -9.1 to
      4.0) but was stable among foreign-born (APC, -0.4; 95% CI, -1.7 to 1.0). A
      statistically significant decreasing trend was observed for squamous cell among
      foreign-born females. CONCLUSIONS: These data provide critical evidence base to
      inform screening, research, and public health priorities in this growing
      population. IMPACT: Given the low smoking prevalence among Chinese Americans,
      especially females, and few known lung cancer risk factors in U.S. never-smoker
      populations, additional research of etiologic genetic or biologic factors may
      elucidate knowledge regarding lung cancer diagnosed in never smokers.

PMID- 25990555
TI  - Assessment of Residual Moisture and Maintenance of Sterility in Surgical
      Instrument Sets after Sterilization.
AB  - Good sterilization practices include discarding items containing residual
      moisture after steam sterilization. In this small laboratory study, however, the
      presence of residual water did not appear to compromise the sterility of surgical
      instruments in 2 commonly used types of packaging during routine storage after
      steam sterilization.

PMID- 25990554
TI  - The impact of DNA input amount and DNA source on the performance of whole-exome
      sequencing in cancer epidemiology.
AB  - BACKGROUND: Whole-exome sequencing (WES) has recently emerged as an appealing
      approach to systematically study coding variants. However, the requirement for a
      large amount of high-quality DNA poses a barrier that may limit its application
      in large cancer epidemiologic studies. We evaluated the performance of WES with
      low input amount and saliva DNA as an alternative source material. METHODS: Five
      breast cancer patients were randomly selected from the Pathways Study. From each
      patient, four samples, including 3 MUg, 1 MUg, and 0.2 MUg blood DNA and 1 MUg
      saliva DNA, were aliquoted for library preparation using the Agilent SureSelect
      Kit and sequencing using Illumina HiSeq2500. Quality metrics of sequencing and
      variant calling, as well as concordance of variant calls from the whole exome and
      21 known breast cancer genes, were assessed by input amount and DNA source.
      RESULTS: There was little difference by input amount or DNA source on the quality
      of sequencing and variant calling. The concordance rate was about 98% for single
      nucleotide variant calls and 83% to 86% for short insertion/deletion calls. For
      the 21 known breast cancer genes, WES based on low input amount and saliva DNA
      identified the same set variants in samples from a same patient. CONCLUSIONS: Low
      DNA input amount, as well as saliva DNA, can be used to generate WES data of
      satisfactory quality. IMPACT: Our findings support the expansion of WES
      applications in cancer epidemiologic studies where only low DNA amount or saliva
      samples are available.

PMID- 25990557
TI  - DSigDB: drug signatures database for gene set analysis.
AB  - We report the creation of Drug Signatures Database (DSigDB), a new gene set
      resource that relates drugs/compounds and their target genes, for gene set
      enrichment analysis (GSEA). DSigDB currently holds 22 527 gene sets, consists of
      17 389 unique compounds covering 19 531 genes. We also developed an online DSigDB
      resource that allows users to search, view and download drugs/compounds and gene
      sets. DSigDB gene sets provide seamless integration to GSEA software for linking
      gene expressions with drugs/compounds for drug repurposing and translational
      research. AVAILABILITY AND IMPLEMENTATION: DSigDB is freely available for non
      commercial use at http://tanlab.ucdenver.edu/DSigDB. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online. CONTACT:
      aikchoon.tan@ucdenver.edu.

PMID- 25990556
TI  - Diverse functions of miR-373 in cancer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post
      transcriptionally. They are involved in almost all cellular processes, and many
      have been described as potential oncogenes or tumor suppressors. MicroRNA-373
      (miR-373), which was first identified as a human embryonic stem cell (ESC)
      specific miRNA, is suggested to be implicated in the regulation of cell
      proliferation, apoptosis, senescence, migration and invasion, as well as DNA
      damage repair following hypoxia stress. Deregulation of miR-373 has been
      demonstrated in a number of cancers, whether it acts as an oncogene or a tumor
      suppressor, however, seems to be context dependent. In this review, we focus on
      the diverse functions of miR-373 and its implication in cancers.

PMID- 25990558
TI  - Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or 'ecstasy' and self
      focused compassion: Preliminary steps in the development of a therapeutic
      psychopharmacology of contemplative practices.
AB  - 3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social
      effects. Cognitive training methods rooted in Eastern contemplative practices
      also produce these effects through the development of a compassionate mindset.
      Given this similarity, we propose that one potential mechanism of action of MDMA
      in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e.
      pro-social attitudes towards the self). We provide a preliminary test of this
      idea. Recreational MDMA (ecstasy) users were tested on two occasions, having
      consumed or not consumed ecstasy. Self-critical and self-compassionate responses
      to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy
      use (or non-use), and then after compassionate imagery (T3). Moderating roles of
      dispositional self-criticism and avoidant attachment were examined. Separately,
      compassionate imagery and ecstasy produced similar sociotropic effects, as well
      as increases in self-compassion and reductions in self-criticism. Higher
      attachment-related avoidance was associated with additive effects of
      compassionate imagery and ecstasy on self-compassion. Findings were in line with
      MDMA's neuropharmacological profile, its phenomenological effects and its
      proposed adjunctive use in psychotherapy. However, although conditions were
      balanced, the experiment was non-blind and MDMA dose/purity was not determined.
      Controlled studies with pharmaceutically pure MDMA are still needed to test these
      effects rigorously. 

PMID- 25990559
TI  - Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients
      with knee osteoarthritis: summary of a randomized, placebo-controlled study.
AB  - AIM: To compare the efficacy, tolerability and safety of celecoxib, naproxen and
      placebo in Asian patients with osteoarthritis (OA) of the knee. METHOD: Patients
      of Asian descent with knee OA, aged >= 45 years, in a flare state with a
      functional capacity classification of I-III, received celecoxib 200 mg once
      daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in
      Patient's Assessment of Arthritis Pain (week 6 vs. baseline) was the primary
      endpoint. Secondary endpoints, including Patient's and Physician's Global
      Assessments of Arthritis, Western Ontario and McMaster Universities OA Index
      (WOMAC), use of complementary and alternative medicines, incidence of treatment
      emergent adverse events (TEAEs) and measurements of upper gastrointestinal
      tolerability, were also assessed. RESULTS: Three hundred and sixty-seven patients
      were randomized: 145 to celecoxib, 144 to naproxen and 78 to placebo. Celecoxib
      was as effective as naproxen in reducing OA pain (least squares mean change from
      baseline in visual analogue scale score [standard error] -37.1 [2.0] for
      celecoxib and -37.5 [2.0] for naproxen). Patient's and Physician's Global
      Assessment of Arthritis, WOMAC scores, Pain Satisfaction Scale and Patient Health
      Questionnaire-9 showed statistically significant improvement in active treatment
      groups versus placebo, with the exception of naproxen WOMAC scores. Treatment
      related TEAEs occurred in 19 (13%), 34 (24%) and six (8%) patients in the
      celecoxib, naproxen and placebo groups, respectively. CONCLUSION: Celecoxib and
      naproxen were comparable in their effects to reduce the signs and symptoms of
      knee OA in Asian patients. Celecoxib was shown to be safe and well tolerated in
      this patient population.

PMID- 25990560
TI  - Injury characteristics and outcome of road traffic accident among victims at
      Adult Emergency Department of Tikur Anbessa specialized hospital, Addis Ababa,
      Ethiopia: a prospective hospital based study.
AB  - BACKGROUND: Road traffic injuries are the eighth leading cause of death globally,
      and the leading cause of death for young people. More than a million people die
      each year on the world's roads, and the risk of dying as a result of a road
      traffic injury is highest in Africa. METHODS: A prospective hospital based study
      was undertaken to assess injury characteristics and outcome of road traffic
      accident among victims at Adult Emergency Department of Tikur Anbessa specialized
      hospital, Addis Ababa, Ethiopia. A structured pre-tested questionnaire was used
      to gather the required data. The collected data were analyzed using SPSS version
      20.0. Hierarchical multiple regression analysis was used to identify predictors
      of fatalities among the road traffic crash victims. RESULTS: A total of 230 road
      traffic accident victims were studied. The majority of the study subjects were
      men 165 (71.7%) and the male/female ratio was 2.6:1. The victims' ages ranged
      from 14 to 80 years with the mean and standard deviations of 32.15 and +/- 14.38
      years respectively. Daily laborers (95 (41.3%)) and students (28 (12.2%)) were
      the majority of road traffic accident victims. Head (50.4%) and musculoskeletal
      (extremities) (47.0%) were the most common body region injured. Fractures (78.0%)
      and open wounds (56.5%) were the most common type of injuries sustained. The
      overall length of hospital stay (LOS) ranged from 1 day to 61 days with mean (+/-
      standard deviation) of 7.12 +/- 10.5 days and the mortality rate was 7.4%.
      Hierarchical multiple regression analysis showed that age of the victims (beta =
      0.16, p < 0.05), systolic blood pressure on admission (beta = -0.35, p < 0.001)
      and Glasgow coma scale (beta = -0.44, p < 0.001) were statistically significant
      predictors of fatalities among the victims. CONCLUSIONS: This study showed
      diverse injury characteristics and high morbidity and mortality among the victims
      attending Adult Emergency Department of Tikur Anbessa specialized hospital, Addis
      Ababa, Ethiopia. The findings reflect that road traffic accident is a major
      public health problem. Urgent road traffic accident preventive measures and
      prompt treatment of the victims are warranted in order to reduce morbidity and
      mortality among the victims.

PMID- 25990561
TI  - Recent decrease in typhoon destructive potential and global warming implications.
AB  - Typhoons (tropical cyclones) severely impact the half-billion population of the
      Asian Pacific. Intriguingly, during the recent decade, typhoon destructive
      potential (Power Dissipation Index, PDI) has decreased considerably (by ~ 35%).
      This decrease, paradoxically, has occurred despite the increase in typhoon
      intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we
      show that the stronger negative contributions from typhoon frequency and
      duration, decrease to cancel the positive contribution from the increasing
      intensity, controlling the PDI. Examining the typhoons' environmental conditions,
      we find that although the ocean condition became more favourable (warming) in the
      recent decade, the atmospheric condition 'worsened' at the same time. The
      'worsened' atmospheric condition appears to effectively overpower the 'better'
      ocean conditions to suppress PDI. This stronger negative contribution from
      reduced typhoon frequency over the increased intensity is also present under the
      global warming scenario, based on analysis of the simulated typhoon data from
      high-resolution modelling.

PMID- 25990563
TI  - [Reflections of the Ethics Group of CAMFiC on editorial attention to chronicity].

PMID- 25990562
TI  - Wrist Fracture and Risk of Subsequent Fracture: Findings from the Women's Health
      Initiative Study.
AB  - Wrist fractures are common in postmenopausal women and are associated with
      functional decline. Fracture patterns after wrist fracture are unclear. The goal
      of this study was to determine the frequency and types of fractures that occur
      after a wrist fracture among postmenopausal women. We carried out a post hoc
      analysis of data from the Women's Health Initiative Observational Study and
      Clinical Trials (1993-2010) carried out at 40 US clinical centers. Participants
      were postmenopausal women aged 50 to 79 years at baseline. Mean follow-up
      duration was 11.8 years. Main measures included incident wrist, clinical spine,
      humerus, upper extremity, lower extremity, hip, and total non-wrist fractures and
      bone mineral density (BMD) in a subset. Among women who experienced wrist
      fracture, 15.5% subsequently experienced non-wrist fracture. The hazard for non
      wrist fractures was higher among women who had experienced previous wrist
      fracture than among women who had not experienced wrist fracture: non-wrist
      fracture overall (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.33
      1.48), spine (HR = 1.48, 95% CI 1.32-1.66), humerus (HR = 1.78, 95% CI 1.57
      2.02), upper extremity (non-wrist) (HR = 1.88, 95% CI 1.70-2.07), lower extremity
      (non-hip) (HR = 1.36, 95% CI 1.26-1.48), and hip (HR = 1.50, 95% CI 1.32-1.71)
      fracture. Associations persisted after adjustment for BMD, physical activity, and
      other risk factors. Risk of non-wrist fracture was higher in women who were
      younger when they experienced wrist fracture (interaction p value 0.02).
      Associations between incident wrist fracture and subsequent non-wrist fracture
      did not vary by baseline BMD category (normal, low bone density, osteoporosis). A
      wrist fracture is associated with increased risk of subsequent hip, vertebral,
      upper extremity, and lower extremity fractures. There may be substantial missed
      opportunity for intervention in the large number of women who present with wrist
      fractures.

PMID- 25990564
TI  - Predator-prey interactions, flight initiation distance and brain size.
AB  - Prey avoid being eaten by assessing the risk posed by approaching predators and
      responding accordingly. Such an assessment may result in prey-predator
      communication and signalling, which entail further monitoring of the predator by
      prey. An early antipredator response may provide potential prey with a selective
      advantage, although this benefit comes at the cost of disturbance in terms of
      lost foraging opportunities and increased energy expenditure. Therefore, it may
      pay prey to assess approaching predators and determine the likelihood of attack
      before fleeing. Given that many approaching potential predators are detected
      visually, we hypothesized that species with relatively large eyes would be able
      to detect an approaching predator from afar. Furthermore, we hypothesized that
      monitoring of predators by potential prey relies on evaluation through
      information processing by the brain. Therefore, species with relatively larger
      brains for their body size should be better able to monitor the intentions of a
      predator, delay flight for longer and hence have shorter flight initiation
      distances than species with smaller brains. Indeed, flight initiation distances
      increased with relative eye size and decreased with relative brain size in a
      comparative study of 107 species of birds. In addition, flight initiation
      distance increased independently with size of the cerebellum, which plays a key
      role in motor control. These results are consistent with cognitive monitoring as
      an antipredator behaviour that does not result in the fastest possible, but
      rather the least expensive escape flights. Therefore, antipredator behaviour may
      have coevolved with the size of sense organs, brains and compartments of the
      brain involved in responses to risk of predation. 

PMID- 25990566
TI  - Cytokine and growth factor profiling in patients with the metabolic syndrome.
AB  - The metabolic syndrome (MetS) is associated with a pro-inflammatory milieu that
      may partially account for its association with an increased cardiovascular risk.
      We aimed to (1) evaluate the serum concentrations of twelve cytokines and growth
      factors (epidermal growth factor (EGF), interferon-gamma (IFN-gamma), IL-1alpha/
      1beta/-2/-4/-6/-8/-10, monocyte chemoattractant protein-1 (MCP-1), TNF-alpha and
      vascular endothelial growth factor (VEGF)) in 303 individuals with or without the
      MetS; and (2) explore their relationship with the presence of the MetS. Patients
      with the MetS had significantly higher serum concentrations of IFN-gamma, EGF, IL
      1alpha/-1beta/-2/-4/-6/-8/-10, MCP-1 and TNF-alpha, whilst serum VEGF
      concentrations were markedly lower compared with the control group (e.g. 38.55 v.
      82.18 pg/ml; P< 0.05). Amongst these parameters, IFN-gamma and IL-1alpha emerged
      as the most significant independent predictors of the MetS. In conclusion, our
      findings demonstrate that patients with the MetS had an altered blood cytokine
      and growth factor profile that may partially account for its adverse clinical
      outcomes. Further prospective studies in larger multi-centre settings are
      required to unravel the role and association of the emerging biomarkers with the
      MetS and their implication in therapeutic intervention. 

PMID- 25990567
TI  - Place of death of people living with Parkinson's disease: a population-level
      study in 11 countries.
AB  - BACKGROUND: Most people prefer to receive end-of-life care in familiar
      surroundings rather than in hospital. This study examines variation in place of
      death for people dying from Parkinson's disease (PD) across 11 European and non
      European countries. METHODS: Using death certificate data of 2008 for Belgium,
      France, Italy, Hungary, Czech Republic, New Zealand, USA, Canada, Mexico, South
      Korea and Spain for all deaths with PD as an underlying cause (ICD-10 code: G20)
      cross-national differences in place of death were examined. Associations between
      place of death and patient socio-demographic and regional characteristics were
      evaluated using multivariable binary logistic regression analyses. RESULTS: The
      proportion of deaths in hospital ranged from 17% in the USA to 75% in South
      Korea. Hospital was the most prevalent place of death in France (40%), Hungary
      (60%) and South Korea; nursing home in New Zealand (71%), Belgium (52%), USA
      (50%), Canada (48%) and Czech Republic (44%); home in Mexico (73%), Italy (51%)
      and Spain (46%). The chances of dying in hospital were consistently higher for
      men (Belgium, France, Italy, USA, Canada), those younger than 80 years (Belgium,
      France, Italy, USA, Mexico), and those living in areas with a higher provision of
      hospital beds (Italy, USA). CONCLUSIONS: In several countries a substantial
      proportion of deaths from PD occurs in hospitals, although this may not be the
      most optimal place of terminal care and death. The wide variation between
      countries in the proportion of deaths from PD occurring in hospital indicates a
      potential for many countries to reduce these proportions.

PMID- 25990568
TI  - Comparison of posterior correction results between Marfan syndrome scoliosis and
      adolescent idiopathic scoliosis-a retrospective case-series study.
AB  - BACKGROUND: The X-ray films of the patients with Marfan syndrome scoliosis (MSS)
      look like those with adolescent idiopathic scoliosis (AIS). In literature, there
      are many reports on the correction results of AIS, while there are a few studies
      focused on the difference of the correction results between MSS and AIS. This
      study aims to analyze whether there are differences of posterior correction
      surgery in MSS and AIS. METHODS: All the patients included underwent posterior
      correction surgery. The radiographic data, operation duration, estimated blood
      loss, transfusion, fusion levels, and correction rate were retrospectively
      reviewed and analyzed between the two groups. RESULTS: Group MSS included 42
      patients, 11 male and 31 female, with an average age of 15.2 years old. Group AIS
      included 168 patients (ratio, 1:4), 34 male and 134 female, with an average age
      of 14.5 years old. Twenty-three patients in group MSS and 94 patients in group
      AIS were followed up regularly, with an average time of 18.4 and 18.5 months,
      respectively. The mean coronal Cobb angle of the major curve before operation and
      at final follow-up, the correction rate, fusion level, operation duration,
      estimated blood loss during operation, and transfusion between the two groups
      were 60.4 and 57.5 degrees , 14.6 and 15.2 degrees , 76.4 and 74.1%, 11.5 and
      11.0 vertebrae, 4.6 and 4.0 h, 845 and 698 ml, and 1151 and 894 ml, respectively.
      The age, gender ratio, curve type, and coronal Cobb angle of the major curve were
      all matched (all P > 0.05). Group MSS had a longer operation duration and more
      estimated blood loss compared with those of group AIS (both P < 0.05), while
      there was no significant difference in terms of fusion level, transfusion,
      coronal Cobb angle of the major curve at final follow-up, and the correction rate
      (all P > 0.05). CONCLUSIONS: When performing posterior correction for scoliosis,
      the surgeons should be aware that the patients with Marfan syndrome scoliosis had
      more estimated blood loss and longer operation duration than AIS patients, while
      the correction rate was similar.

PMID- 25990569
TI  - Analysis of secondary structural and physicochemical changes in protein-protein
      complexes.
AB  - Conformation switching in protein-protein complexes is considered important for
      the molecular recognition process. Overall analysis of 123 protein-protein
      complexes in a benchmark data-set showed that 6.8% of residues switched over
      their secondary structure conformation upon complex formation. Amino acid residue
      wise preference for conformation change has been analyzed in binding and non
      binding site residues separately. In this analysis, residues such as Ser, Leu,
      Glu, and Lys had higher frequency of secondary structural conformation change.
      The change of helix to coil and sheet to coil conformation and vice versa has
      been observed frequently, whereas the conformation change of helix to extended
      sheet occurred rarely in the studied complexes. Influence of conformation change
      toward the N and C terminal on either side of the binding site residues has been
      analyzed. Further, analysis on phi and psi angle variation, conservation,
      stability, and solvent accessibility have been performed on binding site
      residues. Knowledge obtained from the present study could be effectively employed
      in the protein-protein modeling and docking studies. 

PMID- 25990571
TI  - Rh(III)-Catalyzed Direct Coupling of Azobenzenes with alpha-Diazo Esters: Facile
      Synthesis of Cinnolin-3(2H)-ones.
AB  - The rhodium(III)-catalyzed direct C-H functionalization of azobenzenes with alpha
      diazo compounds is described. These transformations provide the facile and
      efficient construction of C2-alkylated azobenzenes or highly substituted cinnolin
      3(2H)-ones. Furthermore, this protocol leads to the formation of cinnolin-3(2H)
      ones using a diazo derivative of Meldrum's acid. 

PMID- 25990572
TI  - Classification of Chinese Honeys According to Their Floral Origins Using
      Elemental and Stable Isotopic Compositions.
AB  - The objective of this study is to test the feasibility of multi-isotopic and
      elemental analyses combined with chemometric techniques for differentiating the
      botanical origins of major honey products in China. The stable isotope and
      elemental compositions of 57 honey samples from four major floral origins in
      China (i.e., rape honey, acacia honey, vitex honey, and jujube honey) were
      analyzed using stable isotope ratio mass spectrometry (IRMS) and inductively
      coupled plasma mass spectrometry (ICP-MS), respectively. The results showed that
      hydrogen and oxygen isotopes could be more suitable than the carbon isotope for
      discriminating the floral origins of major honeys in China. There were
      significant differences in the contents of most elements between or among
      different floral origins. The combination of IRMS and ICP-MS methods provides the
      most effective and accurate approach (in most cases close to 100% accuracy) for
      classifying Chinese honeys according to their floral origins. 

PMID- 25990573
TI  - Fatigue induced changes to kinematic and kinetic gait parameters following six
      minutes of walking in people with multiple sclerosis.
AB  - PURPOSE: The aim of this study was to examine the effect of 6 min of walking on
      fatigue, exertion and spatiotemporal, kinematic and kinetic gait parameters in
      people with multiple sclerosis (MS). METHODS: Thirty-four people with MS with
      moderate levels of disability completed measures of fatigue, exertion and
      instrumented gait analysis before and after 6-min trials of rest and walking
      (using a modified 6-min walk test, m6MWT). Ten age- and gender-matched healthy
      controls completed analysis before and after the m6MWT. RESULTS: The MS group had
      a significant increase in self-reported fatigue following the m6MWT; however,
      there was no effect on spatiotemporal gait parameters. During stance on the more
      affected side ankle dorsiflexion at initial contact decreased, while knee and hip
      flexor moments and hip power absorption increased. On the less affected side
      ankle and knee power absorption, and hip extensor moment all increased. Healthy
      controls showed increases in joint kinetics likely due to increased walking
      speeds following m6MWT. CONCLUSION: For people with MS, ankle dorsiflexion angle
      reduces at initial contact following walking induced fatigue, while increased
      power absorption at the hip, knee and ankle indicate gait inefficiencies that may
      contribute to higher levels of fatigue and exertion. IMPLICATIONS FOR
      REHABILITATION: The modified 6-min walk test (m6MWT) leads to significant
      increases in self-reported fatigue and exertion in people with MS. Following the
      m6MWT, there is significantly reduced ankle dorsiflexion angle at initial contact
      in the more affected leg in people with MS. This reveals an important walking
      induced kinematic change that should be the target of future orthotic and
      strengthening interventions. In people with MS, increased power absorption
      primarily during the stance phase of gait following the m6MWT reveals important
      walking-induced muscle weakness that should also be monitored in future
      strengthening and gait retraining interventions.

PMID- 25990574
TI  - Few-layer graphene/ZnO nanowires based high performance UV photodetector.
AB  - A graphene and zinc oxide nanowires (G/ZnO NWs) based ultraviolet (UV)
      photodetector presents excellent responsivity and photocurrent gain with
      detectivity. Graphene due to higher charge carrier transport mobility induces
      faster response to UV illumination at the interface between ZnO and graphene with
      improved response and decay times as compared to a ZnO NWs device alone. A linear
      increase is revealed for both the responsivity and photocurrent gain of the G/ZnO
      NWs device with the applied bias. These results suggest that the G/ZnO NWs device
      exhibits great promise for highly efficient UV photodetectors. 

PMID- 25990575
TI  - Speed of eating and 3-year BMI change: a nationwide prospective study of mid-age
      women.
AB  - OBJECTIVE: To conduct the first nationwide population survey to examine the
      associations between changes in speed of eating and weight gain over 3 years. The
      study also explored whether faster eating at baseline was related to healthy
      weight women becoming overweight after 3 years. DESIGN: Longitudinal. At
      baseline, participants were randomly selected from a nationally representative
      sampling frame to participate in a prospective study. Women completed self
      administered baseline questionnaires on demographic and health measures. Self
      reported speed of eating, smoking status, physical activity, menopause status,
      and height and weight were collected at baseline and again 3 years later.
      SETTING: Nationwide study, New Zealand. SUBJECTS: Women (n 1601) aged 40-50 years
      were recruited at baseline from New Zealand electoral rolls. RESULTS: There was
      no evidence of associations between 3-year BMI adjusting for baseline BMI and
      either baseline speed of eating (slower and faster; P=0.524) or change in speed
      of eating (consistently faster eating, consistently slower eating, slower eating
      at baseline but not at 3 years, faster eating at baseline but not at 3 years;
      P=0.845). Of the 488 women with healthy BMI (18.5 to <25.0 kg/m2) at baseline,
      seventy-seven (15.8%) became overweight (BMI>=25.0 kg/m2) after 3 years. Compared
      with those who were slower eaters at baseline, faster eating at baseline did not
      increase the risk of becoming overweight 3 years later (P=0.958) nor did change
      in speed of eating (P=0.236). CONCLUSIONS: Results suggest that once women have
      reached mid-life, faster eating does not predict further weight gain.

PMID- 25990576
TI  - Evidence-based Status of Pulsed Radiofrequency Treatment for Patients with
      Shoulder Pain: A Systematic Review of Randomized Controlled Trials.
AB  - PURPOSE: Review the current evidence-based status of pulsed radiofrequency (PRF)
      treatment for patients with shoulder pain based on randomized controlled trials
      (RCTs) to provide a comprehensive analysis and a balanced view of the strengths
      and weaknesses of this treatment. METHODS: PubMed, EMBASE, the Cochrane Library,
      and ISI Web of Science were searched up to July 2014, using the Boolean operators
      as follows: shoulder pain OR painful shoulder AND pulsed radiofrequency). All
      prospective randomized controlled trials of PRF treatment for patients with
      shoulder pain were retrieved. No limitation of the language or publication year
      existed in our analysis. RESULTS: Five of 114 studies that involved PRF treatment
      met the inclusion criteria of this review article. These studies compared the
      clinical outcomes of PRF with those of other treatments such as intra-articular
      corticosteroid injection and conventional transcutaneous electrical nerve
      stimulation. All the studies reported improvements in passive range of motion
      (PROM), visual analog scale (VAS), and Shoulder Pain and Disability Index (SPADI)
      in PRF treatment that persisted for at least 12 weeks. In addition, no
      complications were reported in all trials. CONCLUSION: The use of PRF treatment
      for patients with shoulder pain was observed to result in good clinical efficacy
      for at least 12 weeks with no complication reported. However, it is still unclear
      from the currently available publications whether PRF is superior to other
      treatment techniques such as intra-articular corticosteroid and conventional
      transcutaneous electrical nerve stimulation.

PMID- 25990577
TI  - Menstrual characteristics and ultrasonographic uterine cavity measurements
      predict bleeding and pain in nulligravid women using intrauterine contraception.
AB  - STUDY QUESTION: Is small uterine cavity size as assessed by ultrasonography
      associated with bleeding problems or pain in nulligravid women using intrauterine
      contraception, or do other factors affect these parameters? SUMMARY ANSWER: Among
      levonorgestrel intrauterine system (LNG-IUS) users, small uterine cavity size is
      not associated with worsened clinical outcome, but is beneficial as women with
      the smallest cavity measurements were frequently amenorrhoeic and painless at the
      end of the first year but among copper intrauterine device (IUD) users, no
      associations between uterine cavity dimensions and clinical outcome were found.
      WHAT IS KNOWN ALREADY: Nulligravid and nulliparous women have smaller uterine
      dimensions than parous women. Previously, many studies have revealed increased
      discontinuation rates of IUD use as a result of bleeding, pain or expulsion in
      these women, while recent studies with current models of IUS/IUDs indicate
      similar continuation and satisfaction rates irrespective of parity. STUDY DESIGN,
      SIZE, DURATION: In a pilot study, 165 adult nulligravid women requesting their
      first IUD between 1 January 2011 and 31 July 2012 were given a free choice
      between two IUDs with equal frames measuring 32 * 32 mm-the LNG-IUS 52 mg or a
      copper-releasing IUD. The women were followed for 1 year. PARTICIPANTS/MATERIAL,
      SETTING, METHODS: The LNG-IUS was chosen by 113 women (68.5%) and the copper IUD
      by 52 (31.5%). Prior to insertion the women were interviewed concerning their
      menstrual characteristics and uterine cavity size was measured by 2-D
      ultrasonography. After insertion the women kept daily records of bleeding and
      pain for two reference periods of 90 days during the first year (Months 1-3 and
      10-12). The correlation between uterine cavity measurements and numbers of days
      of bleeding/spotting and pain during the reference periods was analysed.
      Continuation rates were assessed and reasons for discontinuation as well as the
      effects of baseline participant characteristics on outcomes were analysed in
      regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Both uterine cavity size
      and baseline menstrual characteristics prior to IUD insertion predicted the
      numbers of days of bleeding/spotting and pain in LNG-IUS users. Women with small
      uterine cavity dimensions reported less bleeding/spotting in both reference
      periods and less pain in the second reference period compared with women with
      larger dimensions. Baseline scanty spontaneous menstrual bleeding prior to LNG
      IUS use (OR 9.4, 95% CI 1.7-51.8, P = 0.01) and smoking (OR 7.8, 95% CI 1.8-33.8,
      P = 0.006) predicted amenorrhoea in the second reference period. Women with
      baseline dysmenorrhoea reported more pain with both IUDs. Continuation rates and
      reasons for discontinuation were similar with both IUDs. LIMITATIONS, REASONS FOR
      CAUTION: No sample size could be calculated to estimate the power as this was a
      pilot study. As the majority of women chose the LNG-IUS we did not achieve our
      initial aim of equally sized IUD groups and thus the size of the copper IUD group
      may have been insufficient to detect differences. WIDER IMPLICATIONS OF THE
      FINDINGS: These data further encourage promotion of intrauterine contraception
      among nulligravid women. Routine use of ultrasonography to assess uterine cavity
      dimensions prior to IUD insertion is not indicated. STUDY FUNDING/COMPETING
      INTERESTS: Supported by Helsinki University Central Hospital research funds, the
      Swedish Cultural Foundation in Finland and Finska Lakaresallskapet, who provided
      funds for J.K. O.H. serves on advisory boards for Bayer Healthcare, Gedeon
      Richter and MSD Finland (part of Merck & Co. Inc.) and has designed educational
      events with these companies. S.S. has lectured in educational events at Bayer and
      MSD Finland (part of Merck & Co. Inc.) and is a member of the Advisory Board for
      Contraception at MSD Finland. The other authors have no conflicts of interest to
      declare. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov, NCT01685164.

PMID- 25990578
TI  - Investigating the relationship between vitamin D and cancer requires dosing the
      bioavailable nonhydroxylated vitamin D storage in cancer tissues.

PMID- 25990579
TI  - Surgical Management of Freiberg's Infraction: A Systematic Review.
AB  - Avascular necrosis of the second metatarsal head was first described by Freiberg
      in 1913. Conservative treatment includes nonsteroidal anti-inflammatory
      medication, reduced activity, padding, orthotics, and immobilization. Should
      conservative treatment fail, a wide variety of surgical procedures exist;
      however, the optimal procedure is unknown. This systematic review was undertaken
      to determine which surgical procedure allows for the best resolution of symptoms
      and return to activity. Included studies were restricted to articles published in
      English language peer-reviewed journals that consecutively enrolled patients of
      all ages, with Freiberg's infraction of any stage, who underwent operative
      treatment, and had a mean follow-up of greater than or equal to 12 months
      duration. Eighty-five publications were identified, of which 38 (44.7%) met all
      the inclusion criteria. Surgical techniques and outcomes were grouped into joint
      sparing and joint destructive procedures. A total of 70 joint destructive
      procedures were performed with a combined mean follow-up time of 15.0 months. A
      greater than 70% resolution of pain and full return to activity was reported. A
      total of 257 joint sparing procedures were performed with a combined mean follow
      up of 30.4 months. A greater than 90% resolution of pain and full return to
      activity was reported. Results of this systematic review reveal that the results
      of joint sparing procedures are reported more often and appear to have a better
      prognosis for symptom resolution and return to activity. Smillie stage was not
      consistently reported, making it difficult to determine its effect on procedure
      selection. LEVEL OF EVIDENCE: Therapeutic, Level IV: Systematic review of Level
      IV studies.

PMID- 25990581
TI  - 53rd Symposium of International Society for Clinical Electrophysiology of Vision
      (ISCEV).

PMID- 25990580
TI  - A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7
      agonist prevents the growth and metastasis of testis embryonic carcinoma.
AB  - BACKGROUND: The immune non-recognition is often the underlying cause of failure
      in tumor immunotherapeutic. This is because most tumor-related antigens are
      poorly immunogenic, and fail to arouse an efficient immune response against
      cancers. Here we synthesized a novel TLR7 agonist, and developed a safe and
      effective immunotherapeutic vaccine by conjugating this TLR7 agonist with the
      pluripotency antigen OCT4. METHODS: Purified recombinant OCT4 protein was
      covalently linked with a novel TLR7 agonist to form a TLR7-OCT4 conjugate (T7
      OCT4). After conjugation, the in vitro release of IL-12 and IFN-gamma was
      observed in spleen lymphocytes. Mice were immunized with TLR7-OCT4, and the
      release of IFN-gamma, the percentages of CD3+/CD8+ T cells and the OCT4-specific
      cytotoxicity rates were measured. The immunized mice were challenged with mouse
      embryonic carcinoma (EC), and the tumor volume and tumor weight were determined.
      Blood routine examination was performed to evaluate the biosafety of TLR7 agonist
      and TLR7-OCT4 conjugate in mice. RESULTS: T7-OCT4 conjugate significantly
      increased the in vitro release of IL-12 and IFN-gamma by mouse spleen
      lymphocytes. In addition, the release of IFN-gamma, the percentages of CD3+/CD8+
      T cells and the tumor-specific cytotoxicity rates in immunized mice were
      significantly higher. Importantly, in EC xenografted mice, immunization with T7
      OCT4 conjugate decreased the growth of the tumor dramatically up to 90 %, as
      compared to mice immunized with OCT4 protein or TLR7 agonist alone. Furthermore,
      blood routine examination demonstrated that no abnormalities of the blood cells
      and components in the blood fluids were detected by T7-OCT4 and TLR7 agonist
      injections. CONCLUSIONS: Our results showed that conjugating OCT4 protein to the
      novel TLR7 agonist produced a vaccine which is effective and safe in preventing
      tumor growth in mice. Our results suggest that this type of vaccine formulation
      has great potentiality in preventive vaccines against OCT4 expressing tumors.

PMID- 25990583
TI  - The current state of knowledge of ecosystems and ecosystem services in Russia: A
      status report.
AB  - This paper focusses on a conceptual overview of ways to address a comprehensive
      analysis of ecosystem services (ES) in a country as large and heterogeneous as
      Russia. As a first step, a methodology for assessing the services for the federal
      subjects of Russia was chosen, i.e., its constituent provinces and similar
      entities, in physical terms. Russia harbors a great diversity of natural
      conditions and ecosystems which are suppliers of ES, and likewise a variety of
      the socio-economic conditions that shape the demand for these services and their
      consumption. The methodological approach described permits several important
      tasks to be addressed: the evaluation of the degree of satisfaction of people's
      needs for ES, the identification of ecological donor and acceptor regions, and
      zoning of the country's territory for ES assessment. The next step is to prepare
      a prototype of a National Report on ES in Russia, for which we are presenting the
      planned structure. 

PMID- 25990584
TI  - Increasing nitrogen limitation in the Bothnian Sea, potentially caused by inflow
      of phosphate-rich water from the Baltic Proper.
AB  - The study showed that the open water of the Bothnian Sea (BS) is likely to have
      shifted from altering nitrogen and phosphorous limitations of the spring bloom to
      more nitrogen-limited conditions during the last 20 years. This is affected by
      the by inflow of phosphate-rich and oxygen-depleted water from depths near the
      halocline in the northern Baltic Proper, where severe oxygen conditions currently
      cause extreme phosphate concentrations in the deep water. The change in relation
      between inorganic nitrogen and phosphorous in the BS occurs first in the deep
      water and then progresses to the surface water. The change can potentially cause
      increased production in the BS and more frequent cyanobacterial blooms. There
      does not appear to be any immediate concern in the short-term perspective for the
      state of the BS, but a progression of the processes may lead to a more eutrophic
      state of the BS.

PMID- 25990585
TI  - Decolonizing nursing ethics.

PMID- 25990586
TI  - Educating future nurses for global health.

PMID- 25990587
TI  - Health and nursing in all policies.

PMID- 25990589
TI  - Lipid lowering for primary prevention of stroke in older adults?

PMID- 25990590
TI  - Results of a phase I/II open-label, safety and efficacy trial of coagulation
      factor IX (recombinant), albumin fusion protein in haemophilia B patients.
AB  - INTRODUCTION: rIX-FP is a coagulation factor IX (recombinant), albumin fusion
      protein with more than fivefold half-life prolongation over other standard factor
      IX (FIX) products available on the market. AIM: This prospective phase II, open
      label study evaluated the safety and efficacy of rIX-FP for the prevention of
      bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy
      for on-demand treatment of bleeding episodes in previously treated patients with
      haemophilia B. METHODS: The study consisted of a 10-14 day evaluation of rIX-FP
      pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with
      subjects receiving weekly prophylaxis treatment. Safety was evaluated by the
      occurrence of related adverse events, and immunogenic events, including
      development of inhibitors. Efficacy was evaluated by annualized spontaneous
      bleeding rate (AsBR), and the number of injections to achieve haemostasis.
      RESULTS: Seventeen subjects participated in the study, 13 received weekly
      prophylaxis and 4 received episodic treatment only. No inhibitors were detected
      in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the
      weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections
      of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study
      entry had >85% reduction in AsBR compared to the bleeding rate prior to study
      entry. CONCLUSION: This study demonstrated the efficacy for weekly routine
      prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the
      treatment of bleeding episodes. In addition no safety issues were detected during
      the study and an improved PK profile was demonstrated.

PMID- 25990591
TI  - BSA modification to reduce CTAB induced nonspecificity and cytotoxicity of
      aptamer-conjugated gold nanorods.
AB  - Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted
      hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs,
      aptamer conjugation alone fails to result in highly cell-specific AuNRs due to
      the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a
      templating surfactant. Besides causing nonspecific electrostatic interactions
      with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell
      death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB,
      we report the further biologically inspired modification of aptamer-conjugated
      AuNRs with bovine serum albumin (BSA) protein. Following this modification,
      interaction between CTAB and the cell surface was efficiently blocked, thereby
      dramatically reducing the side effects of CTAB. This approach may provide a
      general and simple method to avoid one of the most serious issues in biomedical
      applications of nanomaterials: nonspecific binding of the nanomaterials with
      biological cells. 

PMID- 25990592
TI  - Optimizing informed consent in living liver donors: Evaluation of a comprehension
      assessment tool.
AB  - Adult-to-adult living liver donation is associated with considerable risks with
      no direct medical benefit to liver donors (LDs). Ensuring that potential LDs
      comprehend the risks of donation is essential to medically and ethically justify
      the procedure. We developed and prospectively evaluated the initial psychometrics
      of an "Evaluation of Donor Informed Consent Tool" (EDICT) designed to assess LDs'
      comprehension about the living donation process. EDICT includes 49
      true/false/unsure items related to LD informed consent. Consecutive LDs
      undergoing evaluation at 1 academic medical center from October 2012 to September
      2014 were eligible for participation in pretest/posttest interviews. Medical
      records were reviewed for postdonation complications. Twenty-seven LDs
      participated (96% participation rate). EDICT demonstrated good internal
      consistency reliability at pretest, 2 days before donating (Cronbach's alpha =
      0.78), and posttest, 1 week after donating (alpha = 0.70). EDICT scores
      significantly increased over time (P = 0.01) and demonstrated good test-retest
      reliability (r = 0.68; P < 0.001). EDICT was associated with race/ethnicity (P =
      0.02) and relationship to the recipient (P = 0.01; pretest), and income (P =
      0.01) and insurance (P = 0.01; posttest), but not with decisional conflict,
      preoperative preparedness, satisfaction, or decisional regret (pretest and
      posttest). Donor complications did not impact postdonation EDICT scores. In
      conclusion, EDICT has promising measurement properties and may be useful in the
      evaluation of informed consent for potential LDs.

PMID- 25990593
TI  - Preschool Wheeze is Not Asthma: A Clinical Dilemma - Correspondence.

PMID- 25990595
TI  - Retinal Vasculitis in Kawasaki Disease.

PMID- 25990594
TI  - Management of Shock in Neonates.
AB  - Shock is characterized by inadequate oxygen delivery to the tissues, and is more
      frequent in very low birth weight infants, especially in the first few days of
      life. Shock is an independent predictor of mortality, and the survivors are at a
      higher risk of neurologic impairment. Understanding the pathophysiology helps to
      recognize and classify shock in the early compensated phase and initiate
      appropriate treatment. Hypovolemia is rarely the primary cause of shock in
      neonates. Myocardial dysfunction is especially common in extremely preterm
      infants, and in term infants with perinatal asphyxia. Blood pressure measurements
      are easy, but correlate poorly with cerebral and systemic blood flows. Point-of
      care cardiac ultrasound can help in individualized assessment of problems,
      selecting appropriate therapy and monitoring response, but may not always be
      available, and long-term benefits need to be demonstrated. The use of near
      infrared spectroscopy to guide treatment of neonatal shock is currently
      experimental. In the absence of hypovolemia, excessive administration of fluid
      boluses is inappropriate therapy. Dobutamine and dopamine are the most common
      initial inotropes used in neonatal shock. Dobutamine has been shown to improve
      systemic blood flow, especially in very low birth weight infants, but dopamine is
      better at improving blood pressure in hypotensive infants. Newer inodilators
      including milrinone and levosimendan may be useful in selected settings. Data on
      long-term survival and neurologic outcomes following different management
      strategies are scarce and future research efforts should focus on this. 

PMID- 25990596
TI  - Caroli's Syndrome with Incidental Fibrolamellar Carcinoma on Liver Explant.

PMID- 25990597
TI  - Isolated Cerebellitis in Scrub Typhus.

PMID- 25990598
TI  - Franciscus Cornelis Donders (1818-1889).
AB  - Franciscus Cornelis Donders was educated at Duizel and Boxmeer before entering
      the Military Medical School and the medical faculty at Utrecht University in
      1835. In 1840, he received his MD from Leiden and spent 2 years in practice at
      Vlissingen before returning to Utrecht, where he was appointed as an
      extraordinary professor to lecture on forensic medicine, anthropology, general
      biology and ophthalmology. Refraction by the eye is complex, since the ray of
      light passes through many changes of refractive index in its path, and Donders
      simplified the account of the process by establishing an equivalent refractive
      system: the reduced eye. When Donders opened an Eye Hospital in 1858, he devoted
      himself to clinical ophthalmology, making fundamental advances in providing
      spectacles to correct errors of refraction-which he separated from errors of
      accommodation. In 1862, Donders was promoted as an ordinary professor at Utrecht
      and he handed over the greater part of his practice to his pupil Hermann Snellen.
      From narrow specialisation, Donders was freed to return to the broader
      physiology; subatmospheric pressure in the pleura was for a while referred to as
      'Donders' pressure'; he also devised a method of measuring the mental reaction
      time taken in making discrimination, rather than the simple reaction time in
      which no choice is involved. He was widely honoured, presiding at international
      congresses, and elected as a foreign member of the Royal Society. He died
      suddenly on 14 March 1889, but his work lives on.

PMID- 25990599
TI  - Effects of 3-dimensional culture conditions (collagen-chitosan nano-scaffolds) on
      maturation of dendritic cells and their capacity to interact with T-lymphocytes.
AB  - In the body, there is a natural three-dimensional (3D) microenvironment in which
      immune cells, including dendritic cells (DC), play their functions. This study
      evaluated the impact of using collagen-chitosan 3D nano-scaffolds in comparisons
      to routine 2D culture plates on DC phenotype and functions. Bone marrow-derived
      DC were cultured on scaffolds and plates and then stimulated with
      lipopolysaccharide (LPS) or chitosan-based nanoparticles (NP) for 24 h.
      Thereafter, DC viability, expression of maturation markers and levels of
      cytokines secretion were evaluated. In another set of studies, the DC were co
      cultured with allogenic T-lymphocytes in both the 2D and 3D systems and effects
      on DC-induction of T-lymphocyte proliferation and cytokine release were analyzed.
      The results indicated that CD40, CD86 and MHC II marker expression and
      interleukin (IL)-12, IL-6 and tumor necrosis factor (TNF)-alpha secretion by DC
      were enhanced in 3D cultures in comparison to by cells maintained in the 2D
      states. The data also showed that DNA/chitosan NP activated DC more than LPS in
      the 3D system. T-Lymphocyte proliferation was induced to a greater extent by
      DNA/NP-treated DC when both cell types were maintained on the scaffolds.
      Interestingly, while DC induction of T-lymphocyte interferon (IFN)-gamma and IL-4
      release was enhanced in the 3D system (relative to controls), there was a
      suppression of transforming growth factor (TGF)-beta production; effects on IL-10
      secretion were variable. The results here suggested that collagen-chitosan
      scaffolds could provide a pro-inflammatory and activator environment to perform
      studies to analyze effects of exogenous agents on the induction of DC maturation,
      NP uptake and/or cytokines release, as well as for the ability of these cells to
      potentially interact with other immune system cells in vitro. 

PMID- 25990600
TI  - Comparative human and mouse antibody responses against tetanus toxin at clonal
      level.
AB  - Tetanus is a highly fatal disease caused by tetanus neurotoxin (TeNT) and remains
      a major threat to human and animal health, despite preventive strategies. TeNT is
      composed of heavy and light chain linked by a disulfide bond. The antibody
      response to TeNT is polyclonal and directed to multiple epitopes within both the
      light and heavy chains, leading to toxin neutralization. This study was
      undertaken to localize and compare neutralizing epitopes recognized by human and
      mouse TeNT-specific antibodies at a clonal level. In the present study, 22 murine
      hybridoma clones and 50 human lymphoblastoid cell lines secreting monoclonal
      antibodies (mAb) were generated against TeNT. The specificity of these mAb was
      determined using different recombinant fragments of tetanus toxin. Moreover, this
      study investigated the in vitro toxin neutralizing activity of these mAb by a
      ganglioside GT1b assay. The results showed that tetanus toxoid immunization in
      humans and BALB/c mice induced a vigorous humoral immune response against
      different fragments of TeNT, particularly the carboxyl-terminal fragment of the
      heavy chain (known as fragment C). The fragment C-specific human and mouse mAb
      could largely neutralize TeNT. However, while all fragment C-specific human mAb
      reacted with the carboxyl-terminal part of this fragment (H(CC)), the majority of
      the mouse mAb failed to recognize this region. These results suggested that
      fragment C is the major target for the TeNT neutralizing antibodies, although
      different epitopes seem to be targeted by human and mouse antibodies.

PMID- 25990601
TI  - Validation of the factor structure of the Greek adaptation of the Situational
      Inventory of Body-Image Dysphoria-Short Form (SIBID-S).
AB  - PURPOSE: Body image is a psychological construct that refers to one's
      perceptions, feelings, and thoughts towards one's body and appearance. The
      intensity and frequency of dysphoric body-image emotions depend upon situational
      events (i.e., situations involving body exposure, social comparisons, wearing
      certain clothing, looking in the mirror, and so forth). The Situational Inventory
      of Body-Image Dysphoria-Short Form (SIBID-S; Cash, Manual for the situational
      inventory of body-image dysphoria, 2000) was originally developed to assess one's
      negative body-image emotions in certain situational events. The current study
      aimed to confirm the factor structure and reliability of the newly translated
      Greek version of the SIBID-S. METHODS: Participants consisted of a convenient
      sample of 2664 high school students (1119 males, 1545 females) who answered the
      measures of interest. RESULTS: Results indicated that the original one-factor
      structure of the SIBID-S was retained and fitted very well with the original
      model for both males and females. In addition, the Greek version had satisfactory
      reliability and convergent validity coefficients. Gender differences were also
      noted. CONCLUSION: The Greek SIBID-S has very good validity and reliability data
      and will serve as a useful measure of body-image dysphoria enabling research with
      the Greek-speaking population as well as cross-cultural research.

PMID- 25990602
TI  - Therapeutic antibodies: Discovery, design and deployment.
AB  - Therapeutic antibodies have come of age with major progress being made in cancer,
      autoimmunity and chronic inflammation, as well as a wide range of other human
      diseases. Antibody engineering is further driving development of novel antibody
      formats and genetically modified cell-based therapies that harness the power of
      the immune system to progress cures in otherwise intractable human diseases.
      Nevertheless, there are still significant challenges ahead for basic and applied
      research relating to therapeutic antibodies. This special issue of the journal
      provides reviews and opinions that relate to the discovery, design and deployment
      of antibodies as therapeutics. 

PMID- 25990603
TI  - Validity of the geriatric depression scale and the collateral source version of
      the geriatric depression scale in nursing homes.
AB  - BACKGROUND: Depression is a common psychiatric disorder in older people. The
      study aimed to examine the screening accuracy of the Geriatric Depression Scale
      (GDS) and the Collateral Source version of the Geriatric Depression Scale (CS
      GDS) in the nursing home setting. METHODS: Eighty-eight residents from 14 nursing
      homes were assessed for depression using the GDS and the CS-GDS, and validated
      against clinician diagnosed depression using the Semi-structured Clinical
      Diagnostic Interview for DSM-IV-TR Axis I Disorders (SCID) for residents without
      dementia and the Provisional Diagnostic Criteria for Depression in Alzheimer
      Disease (PDCdAD) for those with dementia. The screening performances of five
      versions of the GDS (30-, 15-, 10-, 8-, and 4-item) and two versions of the CS
      GDS (30- and 15-item) were analyzed using receiver operating characteristic (ROC)
      curves. RESULTS: Among residents without dementia, both the self-rated (AUC =
      0.75-0.79) and proxy-rated (AUC = 0.67) GDS variations performed significantly
      better than chance in screening for depression. However, neither instrument
      adequately identified depression among residents with dementia (AUC between 0.57
      and 0.70). Among the GDS variations, the 4- and 8-item scales had the highest AUC
      and the optimal cut-offs were >0 and >3, respectively. CONCLUSIONS: The validity
      of the GDS in detecting depression requires a certain level of cognitive
      functioning. While the CS-GDS is designed to remedy this issue by using an
      informant, it did not have adequate validity in detecting depression among
      residents with dementia. Further research is needed on informant selection and
      other factors that can potentially influence the validity of proxy-based measures
      in the nursing home setting.

PMID- 25990604
TI  - Correlation between Trypanosoma cruzi parasitism and myocardial inflammatory
      infiltrate in human chronic chagasic myocarditis: Light microscopy and
      immunohistochemical findings.
AB  - Trypanosoma cruzi parasites are only rarely identified in conventional
      histological sections of hearts from chronic chagasic patients. This finding
      suggests that T. cruzi plays no important direct role in the chronic myocarditis
      that accordingly has been considered mainly an autoimmune process. We
      reinvestigated this issue using a polyclonal anti-T. cruzi antibody serum to map
      immunohistochemically the T. cruzi antigen(s) in 9 different regions of 8
      necropsy hearts and 24 septal fragments from 24 hearts from chronic chagasic
      patients. T. cruzi antigen(s) were identified in 7 (87%) of the 8 mapped hearts
      and in 14 (58%) of the 24 septal fragments. There was a statistically significant
      correlation between the presence of T. cruzi antigen(s) and moderate or severe
      inflammatory infiltrate (p = 0.005). When staining revealed amastigotes within
      intact myocardial fibers, there was no surrounding inflammatory infiltrate.
      However, when T. cruzi antigen(s) were found in macrophages either as
      amastigotes, diffusely in the macrophages cytoplasm, or free in the interstitium
      as round structures similar to amastigotes, there was a heavy inflammatory
      infiltrate. In the case in which no parasite was detected, a mild inflammatory
      infiltrate was present in the myocardium. Foci of fibrosis did not stain for T.
      cruzi antigen. These findings do not exclude a role of autoimmunity in chronic
      chagasic cardiopathy. However, the striking correlation between the presence of
      T. cruzi antigen(s) with the severity of site of the inflammatory infiltrate
      supports a direct role for the parasite in the perpetuation of myocardial
      inflammation in Chagas' disease. The destruction of microvessels and occasional
      endothelial cells with parasitism among dense inflammatory infiltrate favors the
      concept that microcirculatory injury, induced by T. cruzi, also contributes to
      the lesions of chronic Chagas' disease. 

PMID- 25990605
TI  - The pathology of murine coxsackievirus B3 myocarditis: An in situ hybridization
      study.
AB  - Histologic changes and localization of viral RNA synthesis were studied in
      cardiac sections of outbred immunocompetent (CD-1) and athymic (nude) Swiss mice
      infected with a myocardiac variant of coxsackievirus B3 (CVB3). Viral effects in
      heart tissue sections progressed through four phases in both models. The first
      phase consisted of histologically normal myocardium with scattered myocytes which
      were strongly positive for nascent viral RNA by in situ hybridization using a
      negative strand CVB3 RNA probe. These cells often appeared in clusters. The
      second phase consisted of focal myocarditic lesions with histologic changes of
      cell necrosis with accompanying lymphocytes and histiocytes; the in situ
      hybridization signal was moderate at this stage. Phase 3 demonstrated relatively
      large lesions with inflammatory infiltrate without recognizable myocyte
      cytoplasm; these lesions showed a weak hybridization signal. Healed (phase 4)
      lesions were negative for viral RNA by in situ hybridization and histologically
      were composed of fibroblast infiltrates with a sparse histiocyte infiltrate. RNA
      sequences from the enteroviral VP-1 region were detectable by polymerase chain
      reaction in phases 1 through 3 and some phase 4 lesions in both models. Although
      the time course of lesion formation was different, lesion development progressed
      through similar recognizable phasesin both murine models. There is an intimate
      association between presence of virus and myocarditis lesions in two diverse
      murine models, indicating that the mechanism of lesion formation is most likely a
      cytopathic viral effect and not an autoimmune phenomenon. The lack of
      hybridization signal over healed lesions is most likely attributable to lack of
      sensitivity of the procedure. 

PMID- 25990606
TI  - Pathologic changes in the cardiac interstitium of mice infected with
      encephalomyocarditis virus.
AB  - Patients with myocarditis often develop dilated cardiomyopathy and congestive
      heart failure. Histologically, myocarditis is manifested by rare foci of myocyte
      necrosis with interstitial inflammation, while cardiomyopathy is characterized by
      diffuse interstitial fibrosis, myocyte hypertrophy, and an absence of active
      interstitial inflammation. The relationship between myocardial inflammation and
      interstitial fibrosis is poorly understood. This relationship was examined in
      mice that developed a diffuse interstitial inflammation of the heart over a
      period of 21 days following infection with encephalomyocarditis virus. Typical
      early lesions (day 7) included focal zones of myocytolysis containing mononuclear
      and polymorphonuclear inflammatory cells that were associated with the focal loss
      of reticular fibers. Later pathology (days 14-21) was characterized by a sparse,
      diffuse interstitial myocarditis with little ongoing necrosis. Changes within the
      myocardial interstitium remote from healing necrotic foci were marked by
      reticular fiber thickening and disorganization, often associated with pleomorphic
      fibroblasts. Reticulin fiber deposition was quantitatively increased in sparsely
      inflamed regions of hearts from infected animals as compared to noninflamed
      regions from the same hearts (p < 0.005) or hearts of control animals (p <
      0.001). Scanning electron microscopy revealed interstitial changes that were more
      extensive than indicated by routine staining with hematoxylin and eosin for
      Masson's trichrome. The progressive changes within the cardiac interstitium
      during the development of postmyocarditic cardiomyopathy suggest that direct
      viral infection of fibroblasts or an interaction between the interstitium and
      inflammatory cells and their secreted products may contribute to pathologic
      changes within the interstitial collagen matrix. 

PMID- 25990607
TI  - Ultrastructural calcium distribution and myocardial calcium content in human
      idiopathic dilated cardiomyopathy.
AB  - Myocardial calcium overload in chronic heart failure is still a debatable issue.
      The aim of this study was to investigate the myocardial calcium content and
      intracellular calcium distribution in end-stage dilated cardiomyopathy. The
      explanted hearts of 13 patients (9 male, 4 female, mean age 49 +/- 12 years)
      undergoing heart transplantation because of end-stage dilated cardiomyopathy were
      examined. Samples were obtained from the right and left ventricular free wall and
      from the septum. Calcium and magnesium content were measured by atomic absorption
      spectrophotometry. Ultrastructural calcium distribution was examined in dilated
      cardiomyopathy using the phosphate-pyroantimonate method. Ultrastructural calcium
      distribution was also examined in left ventricular biopsies obtained from 3
      patients (male, mean age 47 +/- 3.6 years) with nonfailing hearts. The number of
      mitochondrial calcium precipitates was estimated morphometrically by a point
      counting method. Myocardial calcium and magnesium content in dilated
      cardiomyopathy did not differ significantly among the right and left ventricles
      and septum ranging from 8.5 to 10.8 mmol/kg dry weight. The phosphate
      pyroantimonate method visualized calcium precipitates being confined to the
      sarcolemma, T-tubules, intercalated disks, and mitochondria in both nonfailing
      myocardium and dilated cardiomyopathy. Because mitochondria may act as buffers of
      cytoplasmic calcium, mitochondrial calcium precipitates served as a criterion for
      a possible cellular calcium overload. No differences in the amount of
      mitochondrial calcium deposits were observed between dilated cardiomyopathy and
      nonfailing hearts. The data suggest that there is no global myocardial calcium
      overload in human eng-stage dilated cardiomyopathy. 

PMID- 25990608
TI  - Pathology of atrioventricular valve dysplasia.
AB  - The congenital heart disease series of the Pathological Museum at La Sapienza
      University of Rome was revised in order to detect specimens featuring
      atrioventricular valve dysplasia (AVVD) in fetuses and infants. Selected for
      study were 67 specimens from a collection of 667 hearts: there were 36 cases of
      isolated tricuspid valve dysplasia (TVD), 11 cases of isolated mitral valve
      dysplasia (MVD), and 20 cases of combined atrioventricular valve dysplasia. All
      the valves were graded according to Becker's criteria, which were
      morphometrically validated. There is an increasing degree of dysplasia in terms
      of differentiation and detachment of the valve from the ventricular wall. The
      concept of AVVD is supported by a substantial morphologic and morphometric
      analogy between TVD and MVD, in spite of some peculiarities of each grade and of
      side-specific anomalies ("mitral arcade" on the left side and grade III dysplasia
      on the right one), probably attributable to differences in the embryonic
      development of the two valves. AVVD is sometimes associated with dysplasia of the
      semilunar valves, in the setting of a polyvalvular disease of possible genetic
      origin. More often it is combined with other defects that cause ventricular
      overload. In such cases, AVVD usually occurs within the overloaded cardiac
      section, as if it were a result of mechanical stress. 

PMID- 25990609
TI  - Endomyocardial biopsy findings after photopheresis treatment of cardiac
      transplant rejection.
AB  - Photopheresis is a potential therapy for allograft rejection in which reinfusion
      of mononuclear cells exposed to ultraviolet-A irradiation after pretreatment with
      8-methoxypsoralen may initiate immunosuppressive responses. Endomyocardial
      biopsies (EMBs) of cardiac transplant recipients with moderate acute rejection
      (IHSLT grades 2 and 3) treated with photopheresis (7 patients/9 treatments) and
      followed for six months or more were evaluated and compared with biopsies of
      patients treated with corticosteroids (7 patients/8 treatments) and followed for
      a similar time period. The first posttreatment EMB showed improvement in 100% of
      corticosteroid-treated patients, compared with 56% of photopheresis-treated
      patients (p < 0.005). Interstitial infiltrates of >90% T-lymphocytes were present
      in a greater percentage of photopheresis-treated patients than in corticosteroid
      treated patients on the first five posttreatment EMBs (p < 0.005) as follows: EMB
      1, 90% vs. 25%; EMB 2, 90% vs. 25%; EMB 3, 78% vs. 0%; EMB 4, 56% vs. 0%, EMB 5,
      56% vs. 0%. Postphotopheresis EMBs also showed giant cell reaction in 1 patient
      and extensive band-like infiltrates in 3 patients. Our results suggest that
      interstitial T-cell infiltrates are more prevalent and persist longer after
      photopheresis than after corticosteroid treatment of heart allograft rejection.
      Whether these T-lymphocytes are alloreactive or mediate immunosuppressive signals
      is unknown. The use of new immunosuppressive therapies may modify endomyocardial
      biopsy findings, requiring adjustment of the diagnostic criteria for assessing
      and grading allograft rejection. 

PMID- 25990610
TI  - Endovascular versus Non-Interventional Therapy for Cervicocranial Artery
      Dissection in East Asian and Non-East Asian Patients: a Systematic Review and
      Meta-analysis.
AB  - Endovascular methods have been increasingly applied in treating cervicocranial
      artery dissection (CCAD). Anti-thrombotic therapy, which is used in non
      interventional care of CCAD patients, has differential effects in East Asian
      patients. Therefore, we aimed to compare the clinical outcomes of endovascular
      versus non-interventional therapy for CCAD in East Asians and non-East Asians. A
      search was performed for studies comparing endovascular and non-interventional
      approaches to CCAD patients. Rates of recovery, disability, and mortality were
      used to assess these approaches in East Asian and non-East Asian patients.
      Subgroup analyses were conducted for CCAD patients with ruptured dissections.
      Eleven East Asian studies and five non-East Asian studies were included. The
      subgroup analyses for CCAD patients with ruptured dissections on mortality (East
      Asian odds ratio [OR] [95% confidence interval [CI]]: 0.24 [0.08-0.71], P = 0.01;
      I(2) = 34%) and good recovery (East Asian OR [95% CI]: 3.79 [1.14-12.60], P =
      0.03; I(2) = 54%) revealed that endovascular therapy is significantly superior to
      non-interventional therapy for East Asians. No differences in treatment effect
      upon mortality, disability, or good recovery outcomes were found for the CCAD
      populations-at-large nor for non-East Asian CCAD patients with ruptured
      dissections. Endovascular therapy appears to be superior to non-interventional
      therapy for East Asian CCAD patients with ruptured dissections. 

PMID- 25990611
TI  - A field trial of a PCR-based Mansonella ozzardi diagnosis assay detects high
      levels of submicroscopic M. ozzardi infections in both venous blood samples and
      FTA card dried blood spots.
AB  - BACKGROUND: Mansonella ozzardi is a poorly understood human filarial parasite
      with a broad distribution throughout Latin America. Most of what is known about
      its parasitism has come from epidemiological studies that have estimated parasite
      incidence using light microscopy. Light microscopy can, however, miss lighter,
      submicroscopic, infections. In this study we have compared M. ozzardi incidence
      estimates made using light microscopy, with estimates made using PCR. METHODS:
      214 DNA extracts made from Large Volume Venous Blood Samples (LVVBS) were taken
      from volunteers from two study sites in the Rio Solimoes region: Codajas [n =
      109] and Tefe [n = 105] and were subsequently assayed for M. ozzardi parasitism
      using a diagnostic PCR (Mo-dPCR). Peripheral finger-prick blood samples were
      taken from the same individuals and used for microscopic examination. Finger
      prick blood, taken from individuals from Tefe, was also used for the creation of
      FTAcard dried blood spots (DBS) that were subsequently subjected to Mo-dPCR.
      RESULTS: Overall M. ozzardi incidence estimates made with LVVBS PCRs were 1.8
      times higher than those made using microscopy (44.9% [96/214] compared with 24.3%
      [52/214]) and 1.5 times higher than the PCR estimates made from FTAcard DBS
      (48/105 versus 31/105). PCR-based detection of FTAcard DBS proved 1.3 times more
      sensitive at diagnosing infections from peripheral blood samples than light
      microscopy did: detecting 24/105 compared with 31/105. PCR of LVVBS reported the
      fewest number of false negatives, detecting: 44 of 52 (84.6%) individuals
      diagnosed by microscopy; 27 of 31 (87.1%) of those diagnosed positive from DBSs
      and 17 out of 18 (94.4%) of those diagnosed as positive by both alternative
      methodologies. CONCLUSIONS: In this study, Mo-dPCR of LVVBS was by far the most
      sensitive method of detecting M. ozzardi infections and detected submicroscopic
      infections. Mo-dPCR FTAcard DBS also provided a more sensitive test for M.
      ozzardi diagnosis than light microscopy based diagnosis did and thus in settings
      where only finger-prick assays can be carried-out, it may be a more reliable
      method of detection. Most existing M. ozzardi incidence estimates, which are
      often based on light microscope diagnosis, are likely to dramatically
      underestimate true M. ozzardi parasitism incidence levels.

PMID- 25990612
TI  - Differential post-prostatectomy cancer-specific survival of occult T3 vs.
      clinical T3 prostate cancer: Implications for managing patients upstaged on
      prostate magnetic resonance imaging.
AB  - PURPOSE/OBJECTIVE: Long-term androgen deprivation therapy (ADT) was proven in
      randomized trials to be superior to short-term ADT for radiation-managed patients
      who have clinical T3 (cT3) disease, but it is unknown whether patients with T3
      disease seen only on magnetic resonance imaging require similarly aggressive
      treatment. We attempted to study this issue by analogy by comparing the long-term
      post-prostatectomy survival of patients with cT3 disease versus cT1/T2 disease
      upstaged to pathologic T3 disease. METHODS: The Surveillance, Epidemiology, and
      End Results (SEER) database was used to identify 60,165 men diagnosed with
      prostate adenocarcinoma between 1995 and 2002 who underwent prostatectomy.
      Prostate cancer-specific mortality (PCSM) was evaluated by stage after adjusting
      for grade, marital status, race, sex, year of diagnosis, and age. RESULTS: The
      median follow-up was 10.5 years. Patients with cT1/T2 but pathologic T3a disease
      had significantly better 10-year PCSM than men with cT3 disease had (3.0% vs.
      9.9%, adjusted hazard ratio [AHR] = 0.420, P<0.001), but they had worse PCSM than
      men with pathologic T2 disease had (3.0% vs. 0.91%, AHR = 2.53, P<0.001). Of
      patients with occult T3a disease, those with low-grade/intermediate-grade disease
      (Gleason score 7 or less) had a slightly higher 10-year PCSM when compared with
      those with pathologic T2 disease (1.34% vs. 0.91%, AHR = 1.69, P<0.001). Patients
      with cT1/T2 and pathologic T3b disease had similar PCSM as men presenting with
      cT3 disease (11.0% vs. 9.86%, AHR = 1.14 [0.862, 1.52], P = 0.353). CONCLUSIONS:
      Patients with occult T3a disease had less than half the risk of PCSM as those
      with cT3 disease, and a subset of those men had similar risk as patients with
      pathologic T2 disease. Therefore, it is possible that radiation-managed patients
      with low-grade/intermediate-grade T3a disease by magnetic resonance imaging only
      might not require long-term ADT. However, patients with occult T3b or high-grade
      occult T3a disease have similar PCSM as that of those presenting with cT3
      disease, so they should be treated as aggressively, including long-course ADT
      when managed by radiation.

PMID- 25990613
TI  - Commentary on: "Satisfaction with information used to choose prostate cancer
      treatment." Gilbert SM, Sanda MG, Dunn RL, Greenfield TK, Hembroff L, Klein E,
      Saigal CS, Pisters L, Michalski J, Sandler HM, Litwin MS, Wei JT. H. Lee Moffitt
      Cancer Center, Tampa, Florida; Department of Urology, Emory University, Atlanta,
      Georgia; Department of Urology, University of Michigan, Ann Arbor, Michigan;
      Department of Psychiatry and Public Health Institute, University of California
      San Francisco, California; Institute for Public Policy and Social Research,
      Michigan State University, Lansing, Michigan; Glickman Urological and Kidney
      Institute, Cleveland Clinic, Cleveland, Ohio; Department of Urology and
      Department of Health Policy and Management, University of California-Los Angeles,
      Los Angeles, California; Department of Urology, University of Texas M.D. Anderson
      Cancer Center, Houston, Texas; Department of Radiation Oncology, Washington
      University School of Medicine, St. Louis, Missouri; Department of Radiation
      Oncology, Cedars-Sinai Medical Center, Los Angeles, California.: J Urol
      2014;191(5):1265-71. doi:10.1016/j.juro.2013.12.008. [Epub 2013 Dec 12].
AB  - PURPOSE: After being diagnosed with prostate cancer men must assimilate
      information regarding the cancer. Satisfaction with information reflects the
      evaluation of information sources used before treatment to select a therapy. We
      describe the use and helpfulness of several information sources available to
      prostate cancer survivors. We also identified factors associated with
      satisfaction with information. MATERIALS AND METHODS: A total of 1,204 men with
      newly diagnosed prostate cancer were enrolled in the prospective, multicenter
      Prostate Cancer Outcomes and Satisfaction with Therapy Quality Assessment study.
      The validated satisfaction with information domain of the Service Satisfaction
      Scale-Cancer was administered to subjects 2 months after treatment. The
      relationship between several factors, such as demographics, socioeconomic
      factors, cancer severity and types of information sources, and satisfaction with
      information were evaluated using multiple regression. RESULTS: Sources of
      information endorsed by subjects varied by race, education and study site. The
      most helpful sources were treatment description by the treating physician
      (33.1%), Internet sites (18.9%) and books (18.1%). In multiple variable models
      patient age (P = 0.005) and information provided by the physician regarding
      outcomes in their patients (P = 0.01) were independently associated with patient
      satisfaction with the information provided. CONCLUSIONS: Various information
      sources were used and endorsed as helpful by subjects, although results for
      physician patients was the only source independently associated with satisfaction
      with information. Providing patients with information about possible or expected
      courses of care and outcomes may improve satisfaction.

PMID- 25990614
TI  - Digital display monitor performance in general dental practice.
AB  - BACKGROUND: The performance of computer displays represents an important factor
      influencing the quality of digital radiographs. The aim of this study was to
      evaluate the performance of computer displays used for the purposes of diagnostic
      radiology in a sample of dental practices in one Australian state. METHODS:
      Twelve dental practices comprising 29 displays elected to participate in a
      detailed performance evaluation of their computer displays according to the AAPM
      TG18 and DICOM part 14 GSDF standards. RESULTS: None of the 29 displays tested
      passed the primary or secondary acceptance criteria developed by the AAPM TG18.
      The greatest contributor to display failure, both prior to and following
      calibration, were specular and diffuse reflection. When the parameter of display
      reflection was ignored, the most frequent parameters contributing to display
      failure following calibration included the primary grade acceptance criteria of
      noise (n = 29, 100%), contrast ratio (n = 9, 31%) and maximum luminance (n = 12,
      41%). However, display calibration resulted in a significant improvement in the
      parameter of contrast response. CONCLUSIONS: This study demonstrated significant
      problems concerning the performance of display monitors in the population
      surveyed. In recognition of the growing utilization of digital imaging in
      dentistry the importance of the computer display should be considered.

PMID- 25990615
TI  - Adrenal function and microbial DNA in noninfected cirrhotic patients with
      ascites: Relationship and effect on survival.
AB  - BACKGROUND: There are few data on clinical relevance of adrenal dysfunction and
      its relationship with occult microbial DNA in noninfected haemodynamically stable
      cirrhotic patients with ascites. AIMS: The aim of this study was to evaluate
      prognostic role of adrenal dysfunction, microbial DNA, and their relationship.
      METHODS: Adrenal function was assessed in 93 consecutive patients following a
      corticotropin stimulation test. Adrenal dysfunction was defined as: basal
      cortisol <10 MUg/dl, delta cortisol <9 MUg/dl, or peak cortisol <18 MUg/dl.
      Microbial DNA was assessed in blood and ascites of 54 consecutive patients.
      Patients were followed up until liver transplantation or death. RESULTS: Adrenal
      dysfunction was not significantly associated with mortality, while the risk of
      death rose significantly with an increase in basal cortisol values (HR 1.13 per 1
      MUl/dl increase; 95% CI 1.01-1.26). Microbial DNA was independently associated
      with reduced survival (HR 8.05, 95% CI 1.57-41.2). In microbial DNA-positive
      patients a significant correlation was found between Model for End-Stage Liver
      Disease (MELD) score and basal cortisol values (Pearson's r=0.5107; p=0.018).
      CONCLUSIONS: Microbial DNA and MELD score, but not adrenal function, were the
      best independent predictors of mortality in noninfected cirrhotic patients with
      ascites. High serum cortisol levels may be a systemic reaction to microbial
      translocation, increasing in parallel with deterioration of liver function.

PMID- 25990616
TI  - Selective Oxidation of 1,6-Hexanediol to 6-Hydroxycaproic Acid over Reusable
      Hydrotalcite-Supported Au-Pd Bimetallic Catalysts.
AB  - Selective oxidation of 1,6-hexanediol into 6-hydroxycaproic acid was achieved
      over hydrotalcite-supported Au-Pd bimetallic nanoparticles as heterogeneous
      catalyst using aqueous H2 O2 . N,N-dimethyldodecylamine N-oxide (DDAO) was used
      as an efficient capping agent. Spectroscopic analyses by UV/Vis, TEM, XPS, and X
      ray absorption spectroscopy suggested that interactions between gold and
      palladium atoms are responsible for the high activity of the reusable Au40 Pd60 
      DDAO/HT catalyst. 

PMID- 25990617
TI  - Thinking about motor fluctuations: An examination of metacognitions in
      Parkinson's disease.
AB  - OBJECTIVE: Motor fluctuations (characterised by a sudden increase in symptom
      intensity, referred to as an 'off-period') are common side effects after
      treatment of Parkinson's disease (PD) with dopaminergic medication. A proportion
      of these people find motor fluctuations highly distressing. This study aimed to
      identify metacognitions associated with cognitive and attentional responses to
      these experiences. METHODS: Ten individuals with PD who experience motor
      fluctuations were interviewed for this study using an adapted metacognitive
      profiling schedule. Participants were asked about their metacognitions, and the
      cognitive processes and attentional strategies activated in response to a
      distressing off-period. RESULTS: Metacognitions identified were more often
      related to conceptual thinking about symptoms rather than symptom focus and data
      suggested trends for increased depressive symptoms among individuals with
      stronger metacognitive beliefs. CONCLUSION: Metacognitions may play a role in
      determining or maintaining off-period distress in PD.

PMID- 25990618
TI  - Integrating plant litter quality, soil organic matter stabilization, and the
      carbon saturation concept.
AB  - Labile, 'high-quality', plant litters are hypothesized to promote soil organic
      matter (SOM) stabilization in mineral soil fractions that are physicochemically
      protected from rapid mineralization. However, the effect of litter quality on SOM
      stabilization is inconsistent. High-quality litters, characterized by high N
      concentrations, low C/N ratios, and low phenol/lignin concentrations, are not
      consistently stabilized in SOM with greater efficiency than 'low-quality' litters
      characterized by low N concentrations, high C/N ratios, and high phenol/lignin
      concentrations. Here, we attempt to resolve these inconsistent results by
      developing a new conceptual model that links litter quality to the soil C
      saturation concept. Our model builds on the Microbial Efficiency-Matrix
      Stabilization framework (Cotrufo et al., 2013) by suggesting the effect of litter
      quality on SOM stabilization is modulated by the extent of soil C saturation such
      that high-quality litters are not always stabilized in SOM with greater
      efficiency than low-quality litters. 

PMID- 25990619
TI  - Update on hepatitis C: epidemiology, treatment and resistance to antiviral
      therapies.
AB  - Chronic hepatitis C (HCV) is a major cause of morbidity and mortality due to
      chronic liver disease worldwide. Exposure to the virus leads to chronic infection
      in the majority of cases and may be associated with progression to cirrhosis, end
      stage liver disease and hepatocellular carcinoma. Treatment of HCV has been
      challenging until recently, requiring combination treatment with interferon
      injections and ribavirin, both associated with significant toxicities and
      sustained virologic response (SVR) rates of 50% for most patients. Recent
      advances in therapy have allowed for all-oral treatments with SVR rates >90% with
      as little as 8 weeks of therapy. This review describes the developments in HCV
      therapy over the last two decades, the current treatment regimens and the rates
      of antiviral resistance with the new therapies on the horizon. 

PMID- 25990621
TI  - Chemical modifications and stability of phosphorene with impurities: a first
      principles study.
AB  - We perform a systematic first-principles study of phosphorene in the presence of
      typical monovalent (hydrogen and fluorine) and divalent (oxygen) impurities. The
      results of our modeling suggest a decomposition of phosphorene into weakly bonded
      one-dimensional (1D) chains upon single- and double-side hydrogenation and
      fluorination. In spite of a sizable quasiparticle band gap (2.29 eV), fully
      hydrogenated phosphorene was found to be dynamically unstable. In contrast,
      complete fluorination of phosphorene gives rise to a stable structure, which is
      an indirect gap semiconductor with a band gap of 2.27 eV. We also show that
      fluorination of phosphorene from the gas phase is significantly more likely than
      hydrogenation due to the relatively low energy barrier for the dissociative
      adsorption of F2 (0.19 eV) compared to H2 (2.54 eV). At low concentrations,
      monovalent impurities tend to form regular atomic rows of phosphorene, though
      such patterns do not seem to be easily achievable due to high migration barriers
      (1.09 and 2.81 eV for H2 and F2, respectively). Oxidation of phosphorene is shown
      to be a qualitatively different process. Particularly, we observe instability of
      phosphorene upon oxidation, leading to the formation of disordered amorphous-like
      structures at high concentrations of impurities. 

PMID- 25990620
TI  - The Likelihood of Hospital Readmission Among Patients With Hospital-Onset Central
      Line-Associated Bloodstream Infections.
AB  - OBJECTIVE: To determine whether central line-associated bloodstream infections
      (CLABSIs) increase the likelihood of readmission. DESIGN: Retrospective matched
      cohort study for the years 2008-2009. SETTING: Acute care hospitals.
      PARTICIPANTS: Medicare recipients. CLABSI and readmission status were determined
      by linking National Healthcare Safety Network surveillance data to the Centers
      for Medicare and Medicaid Services' Medical Provider and Analysis Review in 8
      states. Frequency matching was used on International Classification of Diseases,
      Ninth Revision, Clinical Modification procedure code category and intensive care
      unit status. METHODS: We compared the rate of readmission among patients with and
      without CLABSI during an index hospitalization. Cox proportional hazard analysis
      was used to assess rate of readmission (the first hospitalization within 30 days
      after index discharge). Multivariate models included the following covariates:
      race, sex, length of index hospitalization stay, central line procedure code,
      Gagne comorbidity score, and individual chronic conditions. RESULTS: Of the 8,097
      patients, 2,260 were readmitted within 30 days (27.9%). The rate of first
      readmission was 7.1 events/person-year for CLABSI patients and 4.3 events/person
      year for non-CLABSI patients (P<.001). The final model revealed a small but
      significant increase in the rate of 30-day readmissions for patients with a
      CLABSI compared with similar non-CLABSI patients. In the first readmission for
      CLABSI patients, we also observed an increase in diagnostic categories consistent
      with CLABSI, including septicemia and complications of a device. CONCLUSIONS: Our
      analysis found a statistically significant association between CLABSI status and
      readmission, suggesting that CLABSI may have adverse health impact that extends
      beyond hospital discharge.

PMID- 25990622
TI  - Portal Venous Stent Placement for Malignant Portal Venous Stenosis or Occlusion:
      Who Benefits?
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of portal venous
      (PV) stent placement and find groups who benefit from this procedure among
      patients with symptomatic PV hypertension caused by malignant tumors. MATERIALS
      AND METHODS: From October 2001 to January 2013, 13 patients underwent PV stent
      placement because of PV stenosis or occlusion caused by bile duct cancer (n = 7),
      pancreatic cancer (n = 5), or nodal metastasis (n = 1). Technical success,
      changes in PV pressure gradient and palliative prognostic index (PPI) scores
      before and after stent placement, clinical outcomes, and complications were
      evaluated. RESULT: Stent was successfully placed in all patients (100 %, 13/13),
      lowering the mean PV pressure gradient from 12.4 +/- 4.5 mmHg (range 5-20 mmHg)
      to 0.5 +/- 0.9 mmHg (range 0-3 mmHg, p < 0.000001). Symptoms were improved in all
      but one patient (92.3%, 12/13). Although 10 patients (76.9%, 10/13) with pre
      stent placement PPI scores lower than 6 (mean 3.5 +/- 1.7, range 0-5) were
      discharged from the hospital, the other 3 with the pre-stent placement PPI of 6
      or more (mean 7.2 +/- 1.6, range 6-9.5) died within 4 weeks (range 17-28 days)
      without discharge. The median survival time of discharged patients was 123 days,
      and it was 20 days in non-discharged patients (p = 0.0001). A major procedure
      related complication of intraperitoneal hemorrhage occurred in one patient (7.7%,
      1/13). No significant factor was detected for the occurrence of complication.
      CONCLUSION: PV stent placement is a feasible, safe, and effective technique to
      relieve symptomatic PV hypertension caused by malignant tumors. The PPI score
      might be useful to stratify patients who benefit from this procedure.

PMID- 25990623
TI  - Metastasis initiating cells in primary prostate cancer tissues from transurethral
      resection of the prostate (TURP) predicts castration-resistant progression and
      survival of prostate cancer patients.
AB  - BACKGROUND: We previously reported that the activation of RANK and c-Met
      signaling components in both experimental mouse models and human prostate cancer
      (PC) specimens predicts bone metastatic potential and PC patient survival. This
      study addresses whether a population of metastasis-initiating cells (MICs) known
      to express a stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1
      (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected
      in PC tissues from patients subjected to transurethral resection of the prostate
      (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior
      hormonal manipulation, and whether the relative abundance of MICs over BDCs could
      predict castration-resistant progression and PC patient survival. METHODS: We
      employed a multiplexed quantum-dot labeling (mQDL) protocol to detect and
      quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44
      PC patients with documented overall survival and castration resistance status.
      RESULTS: PC tissues with a higher number of MICs and an activated RANK signaling
      network, including increased expression of RANKL, p-c-Met, and NRP1 compared to
      BDCs, were found to correlate with the development of castration resistance and
      overall survival. CONCLUSIONS: The assessment of PC cells with MIC and BDC
      phenotypes in primary PC tissues from hormone-naive patients can predict the
      progression to castration resistance and the overall survival of PC patients.

PMID- 25990624
TI  - Galectin-3 as a new biomarker of diastolic dysfunction in hemodialysis patients.
AB  - BACKGROUND: Galectin-3 (gal-3) is an emerging prognostic biomarker in heart
      failure (HF). Clinical and experimental studies suggest that gal-3 is an
      important mediator of HF. Here we aimed to examine the relationship between gal-3
      and diastolic dysfunction in patients undergoing maintenance hemodialysis (HD).
      METHODS: We examined the relationship between plasma gal-3 levels and left
      ventricular diastolic function. Plasma gal-3 was measured in 87 subjects with
      chronic HD and in 45 healthy controls using biochemical evaluations. Conventional
      echocardiography and pulsed tissue Doppler assessment were performed in all
      patients. Left ventricular diastolic dysfunction (LVDD) was defined as E' < 8
      cm/s. The E/E' ratio was used as the main determinant of LVDD grade. RESULTS: The
      mean gal-3 concentrations were: 16.05 ng/ml (13.89-19.75) in healthy controls;
      14.54 ng/ml (10.85-17.65) in HD patients with normal diastolic function; and
      23.30 ng/ml (20.12-26.87) in HD patients with LVDD (p  < 0.01). Plasma gal-3
      levels correlated with E/E' (r = 0.933, p  < 0.01), left atrial volume index (r =
      0.713, p  < 0.01), and E' (r = -0.685, p  < 0.01). ROC analysis showed that the
      best gal-3 cut-off point for the diagnosis of LVDD was 20.12 ng/ml with a
      sensitivity of 67.6 % and specificity of 84.6 % (AUC = 0.803). CONCLUSION: We
      suggest that gal-3 may be a promising biomarker for the detection of LVDD in HD
      patients.

PMID- 25990625
TI  - Reduction of radiation exposure during ablation of atrial fibrillation.
AB  - AIMS: Pulmonary vein isolation (PVI) during ablation of atrial fibrillation
      (Afib) may be associated with long fluoroscopy duration. Although most current
      publications report on fluoroscopy time (FT), the dose-area product (DAP) may be
      a more valuable parameter for depicting radiation exposure. The aim of our study
      was to describe a method to reduce DAP by simple means during ablation of Afib.
      METHODS: Patients undergoing Afib ablation using a three-dimensional (3D) mapping
      system were assigned to two fluoroscopy protocols: (1) standard settings with 7.5
      pictures/s and collimation to the heart, fluoroscopy as needed for the
      convenience of the operator (standard group, SG); and (2) strict collimation to
      the left atrium, a frame rate of 4 pictures/s, shortened pulmonary vein
      angiography sequences, and maximal orientation by the 3D mapping system (redDAP
      group). The primary endpoint was DAP. RESULTS: The study comprised 206 patients,
      who were assigned to the SG (n = 101, 49 %) or to the redDAP group (n = 105, 51
      %). Mean FT was significantly reduced from 29.9 +/- 11.3 min (SG) to 13.3 +/- 8.3
      min (redDAP group); mean DAP was reduced by approximately 90 % from 8,690 +/-
      5,727 to 837 +/- 647 cGycm(2). The groups did not differ significantly in body
      mass index (28.8 +/- 4.1 vs. 29.0 +/- 5.0). PVI could be achieved in 98 of 101
      patients (97 %) from the SG group and in all patients (100 %) from the redDAP
      group. Procedure time was significantly longer in the redDAP group (160.9 +/-
      35.7 vs. 138.1 +/- 34.3 min). CONCLUSION: Radiation exposure during Afib ablation
      procedures can be reduced with simple means by strict collimation to the left
      atrium, a frame rate of 4 pictures/s, shortened pulmonary vein angiography
      sequences, and maximal 3D orientation.

PMID- 25990627
TI  - Organocatalytic enantio- and diastereoselective synthesis of highly substituted
      delta-lactones via a Michael-cyclization cascade.
AB  - An organocatalyzed Michael-cyclization cascade approach of readily available
      alpha,beta-unsaturated aldehydes and pyrazoleamides has been developed to get
      highly substituted delta-lactones in excellent enantioselectivities (up to 97%)
      and diastereoselectivities. The delta-lactones so obtained could easily be
      transformed into benzazepine derivatives with excellent enantio- and
      diastereoselectivities. Furthermore, the pyrazole moiety from the delta-lactones
      can be simply cleaved without disturbing the stereoselectivity. 

PMID- 25990626
TI  - Prevalence and factors related to left ventricular systolic dysfunction in
      asymptomatic patients with rheumatoid arthritis. A prospective tissue Doppler
      echocardiography study.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have a high risk for
      cardiovascular disease due to a chronic inflammatory state, accelerated
      atherosclerosis, and changes in left ventricular (LV) geometry. These conditions
      predispose patients to LV systolic dysfunction (LVSD). In this study we assessed
      whether RA is a condition associated with LVSD, and analyzed the prevalence and
      factors associated with LVSD in patients with RA. PATIENTS AND METHODS:
      Echocardiographic and clinical data from 198 patients with RA without presence or
      history of symptoms of cardiac disease were compared with 198 non-RA controls
      matched for cardiovascular risk factors. LVSD was identified with tissue Doppler
      echocardiography (TDE) when mitral annular peak systolic velocity (S') was < 9.0
      cm/s. RESULTS: Patients with RA were 61 +/- 12 years old and 71 % were female
      (disease duration 14 +/- 10 years). LVSD was found in 89 patients with RA (45 %).
      By multiple regression analysis including both RA patients and controls, RA
      emerged as an independent condition associated with LVSD (exp beta 3.89; CI: 1.87
      8.08) together with higher E/E' ratio (index of LV diastolic function) and
      diabetes mellitus. For the 198 patients with RA, the variables associated with
      LVSD were higher E/E' ratio and systolic blood pressure. CONCLUSIONS: Almost half
      of asymptomatic RA patients without history of cardiac disease have subclinical
      LVSD easily detectable with TDE. RA is closely related to LVSD. A higher degree
      of LV diastolic dysfunction and systolic blood pressure are associated with LVSD
      in these patients, whose risk for cardiovascular events could be better defined
      using such information in the asymptomatic stage of cardiac disease.

PMID- 25990628
TI  - Toxoplasma gondii seropositivity and cognitive functions in school-aged children.
AB  - Toxoplasma gondii (T. gondii) infects one-third of the world population, but its
      association with cognitive functions in school-aged children is unclear. We
      examined the relationship between Toxoplasma seropositivity and
      neuropsychological tests scores (including math, reading, visuospatial reasoning
      and verbal memory) in 1755 school-aged children 12-16 years old who participated
      to the Third National Health and Nutrition Examination Survey, using multiple
      linear regressions adjusted for covariates. Toxoplasma seroprevalence was 7.7%
      and seropositivity to the parasite was associated with lower reading skills
      (regression coefficient [beta] = -5.86, 95% confidence interval [CI]: -11.11, 
      0.61, P = 0.029) and memory capacities (beta = -0.86, 95% CI: -1.58, -0.15, P =
      0.017). The interaction between T. gondii seropositivity and vitamin E
      significantly correlated with memory scores. In subgroup analysis, Toxoplasma
      associated memory impairment was worse in children with lower serum vitamin E
      concentrations (beta = -1.61, 95% CI: -2.44, -0.77, P < 0.001) than in those with
      higher values (beta = -0.12, 95% CI: -1.23, 0.99, P = 0.83). In conclusion,
      Toxoplasma seropositivity may be associated with reading and memory impairments
      in school-aged children. Serum vitamin E seems to modify the relationship between
      the parasitic infection and memory deficiency. 

PMID- 25990629
TI  - Welfare of organic laying hens kept at different indoor stocking densities in a
      multi-tier aviary system. II: live weight, health measures and perching.
AB  - Multi-tier aviary systems, where conveyor belts below the tiers remove the manure
      at regular intervals, are becoming more common in organic egg production. The
      area on the tiers can be included in the net area available to the hens (also
      referred to as usable area) when calculating maximum indoor stocking densities in
      organic systems within the EU. In this article, results on live weight, health
      measures and perching are reported for organic laying hens housed in a multi-tier
      system with permanent access to a veranda and kept at stocking densities (D) of
      6, 9 and 12 hens/m2 available floor area, with concomitant increases in the
      number of hens per trough, drinker, perch and nest space. In a fourth treatment,
      access to the top tier was blocked reducing vertical, trough, and perch access at
      the lowest stocking density (D6x). In all other aspects than stocking density,
      the experiment followed the EU regulations on the keeping of organic laying hens.
      Hen live weight, mortality and foot health were not affected by the stocking
      densities used in the present study. Other variables (plumage condition, presence
      of breast redness and blisters, pecked tail feathers, and perch use) were
      indirectly affected by the increase in stocking density through the simultaneous
      reduction in access to other resources, mainly perches and troughs. The welfare
      of the hens was mostly affected by these associated constraints, despite all of
      them being within the allowed minimum requirements for organic production in the
      EU. Although the welfare consequences reported here were assessed to be moderate
      to minor, it is important to take into account concurrent constraints on access
      to other resources when higher stocking densities are used in organic production.

PMID- 25990630
TI  - Transformation products of emerging contaminants in the environment and high
      resolution mass spectrometry: a new horizon.
AB  - It is crucial to study the presence of transformation products (TPs) of emerging
      contaminants that can be potentially found in the environment after biological or
      chemical degradation. This review focuses on the potential and shortcomings of
      high-resolution mass spectrometry (HRMS) to identify these TPs, with emphasis on
      recent developments in mass analyzers, data evaluation, and compound
      identification workflows and applications. Advances in HRMS technologies,
      including direct introduction or in-line chromatographic separation modes,
      ionization techniques, mass analyzers, and detection methods, have led to
      powerful tools to assess the molecular changes and the opening of new horizons to
      identify unknown molecules. Advances in HRMS pertaining to the generation of
      analytical data for the main methods to identify TPs, including nontargeted and
      targeted approaches as they are applied to elucidate the structure of TPs, are
      also discussed. 

PMID- 25990631
TI  - Allogeneic hematopoietic stem cell transplantation for refractory Behcet's
      disease with myelodysplastic syndrome: a case report.

PMID- 25990632
TI  - Thermal and inertial resonances in DNA unzipping.
AB  - Single-molecule experiments combined with alternate forces are able to provide
      useful information not present in standard constant-force and -velocity pulling
      protocols. Here, we study the effects of such forces in the DNA mechanical
      unzipping by using an extension of the Peyrard-Bishop-Dauxois model. By changing
      the damping regime in the dynamical equations, we obtained two resonant
      mechanisms in both the mean time and the mean force of unzipping. One is
      thermally assisted and it is characterized by a matching between the period of
      the external force and the mean unzipping time of the DNA chain, while the other
      depends on the inertial properties of the system. Both mechanisms are studied
      systematically under different opening protocols and different parameters of the
      system. The main results here presented contribute in characterizing and finding
      optimized conditions in DNA unzipping experiments. 

PMID- 25990633
TI  - Three-sphere low-Reynolds-number swimmer with a passive elastic arm.
AB  - One of the simplest model swimmers at low Reynolds number is the three-sphere
      swimmer by Najafi and Golestanian. It consists of three spheres connected by two
      rods which change their lengths periodically in non-reciprocal fashion. Here we
      investigate a variant of this model in which one rod is periodically actuated
      while the other is replaced by an elastic spring. We show that the competition
      between the elastic restoring force and the hydrodynamic drag produces a delay in
      the response of the passive elastic arm with respect to the active one. This
      leads to non-reciprocal shape changes and self-propulsion. After formulating the
      equations of motion, we study their solutions qualitatively and numerically. The
      leading-order term of the solution is computed analytically. We then address
      questions of optimization with respect to both actuation frequency and swimmer's
      geometry. Our results can provide valuable conceptual guidance in the engineering
      of robotic microswimmers. 

PMID- 25990634
TI  - The influence of hyperglycemia during radiotherapy on survival in patients with
      primary glioblastoma.
AB  - BACKGROUND AND PURPOSE: Metabolism in tumor cells depends mainly on glycolysis
      and thus hyperglycemia has been shown to influence tumor properties in various
      tumor entities. In this retrospective study we set out to determine if
      hyperglycemic serum levels during radiation therapy impact patient survival and
      progression patterns in primary glioblastoma (GBM). MATERIAL AND METHODS: We
      retrospectively analyzed glucose serum levels, survival and progression patterns
      on magnetic resonance imaging (MRI) in 262 GBM patients receiving radiation
      therapy. Hyperglycemia was classified as mild (> 180 mg/dL) or excessive (>= 300
      mg/dL), and isolated (one hyperglycemic event) or persistent (>= 3 hyperglycemic
      events). The multivariate Cox proportional hazards ratio was used to assess the
      influence of cofactors on survival. RESULTS: Persistent mild (HR = 2.23; p <
      0.001) and excessive hyperglycemia (HR = 2.51; p < 0.001) were associated with a
      decrease in overall survival rates, even when considering the covariate
      corticosteroid therapy. Here metabolic imbalances did not affect the progression
      free interval (p = 0.402), the occurrence of distant (p = 0.587) and multifocal
      progression (p = 0.445). CONCLUSION: Our findings support the theory that
      hyperglycemia during radiation therapy in GBM patients is an unfavorable
      prognostic cofactor for survival and is detrimental to the survival rates
      independent of corticosteroid therapy. However, no significant effects of
      hyperglycemic metabolism on the progression-free interval and recurrence patterns
      were found.

PMID- 25990635
TI  - Public interest in and acceptability of the prospect of risk-stratified screening
      for breast and prostate cancer.
AB  - BACKGROUND: For risk-stratified screening to be implemented as a screening
      program for breast and prostate cancer it has to be accepted among the general
      population. Investigating public interest in stratified screening and its
      acceptability to the public is therefore essential since as yet little is known.
      METHOD: Cross-sectional web survey sent to a sample of 10 000 individuals (20-74
      years of age) representative of the Swedish population as registered in 2009.
      RESULTS: Among the responders (28%), a vast majority (94%) expressed an interest
      in knowing their breast or prostate cancer risk and stated wanting to know to
      'avoid worrying'. Men and women were equally interested in knowing their prostate
      and breast cancer risk, respectively. However, men showed more certainty.
      Trusting the healthcare workers with personal information (63%) as well as
      genetic information (70%), in order to calculate the risk, did not seem to be a
      major issue. Furthermore, 87% would agree to get screened more often if
      identified with a high risk, whereas, if identified with a low risk, only 27%
      would agree to get screened less often. Finally, although a consultation with a
      physician seemed to be the preferred way to communicate the risk, a majority
      would agree to receive it via a letter or a phone call. CONCLUSION: Risk
      stratified screening has the possibility to be accepted by the general public.
      Knowledge about interest and acceptability of the prospect of risk-stratified
      screening for breast and prostate cancer will help when implementing new
      screening strategies.

PMID- 25990636
TI  - Use of tocopherol extract and different nitrite sources and starter cultures in
      the production of organic botifarra catalana, a cooked cured sausage.
AB  - This research evaluates the effects of adding a tocopherol mix (0 or 200 mg/kg),
      two nitrite sources (sodium nitrite or a nitrate-rich vegetable concentrate) and
      the use of Staphylococcus carnosus together with fermentation types that varied
      in temperature (12 h at 4 C or 16 C) on different quality parameters and
      acceptability of cooked cured sausages after vacuum packing and storage at 4 C
      for 120 days. In the presence of S. carnosus, residual nitrate and nitrite levels
      were reduced. Sausages containing vegetable concentrates and without S. carnosus
      resulted in higher amounts of residual nitrate and lower curing efficiency. The
      lowest values in redness and acceptability were observed in those sausages
      without starter cultures. The addition of tocopherols had no effect on oxidative
      status and susceptibility to oxidation. However, the highest amount of
      hydroperoxides was related with nitrite decreased formation. Overall, vegetable
      concentrates can be used as curing agents if fermentation with a nitrate-reducing
      starter culture is allowed.

PMID- 25990638
TI  - Anomalous magnetoresistance in the spinel superconductor LiTi2O4.
AB  - LiTi2O4 is a unique compound in that it is the only known spinel oxide
      superconductor. The lack of high quality single crystals has thus far prevented
      systematic investigations of its transport properties. Here we report a careful
      study of transport and tunnelling spectroscopy in epitaxial LiTi2O4 thin films.
      An unusual magnetoresistance is observed which changes from nearly isotropic
      negative to prominently anisotropic positive as the temperature is decreased. We
      present evidence that shows that the negative magnetoresistance likely stems from
      the suppression of local spin fluctuations or spin-orbit scattering centres. The
      positive magnetoresistance suggests the presence of an orbital-related state,
      also supported by the fact that the superconducting energy gap decreases as a
      quadratic function of magnetic field. These observations indicate that the spin
      orbital fluctuations play an important role in LiTi2O4 in a manner similar to
      high-temperature superconductors. 

PMID- 25990637
TI  - cAMP-dependent protein kinase inhibits alpha7 nicotinic receptor activity in
      layer 1 cortical interneurons through activation of D1/D5 dopamine receptors.
AB  - KEY POINTS: Protein kinases can modify the function of many proteins including
      ion channels. However, the role of protein kinase A in modifying nicotinic
      receptors in the CNS has never been investigated. We showed through whole-cell
      recordings of layer 1 prefrontal cortical interneurons that alpha7 nicotinic
      responses are negatively modulated by protein kinase A. Furthermore, we show that
      stimulation of dopamine receptors can similarly attenuate alpha7 nicotinic
      responses through the activation of protein kinase A. These results suggest how
      the interaction of the cholinergic and dopaminergic systems may influence
      neuronal excitability in the brain. ABSTRACT: Phosphorylation of ion channels,
      including nicotinic acetylcholine receptors (nAChRs), by protein kinases plays a
      key role in the modification of synaptic transmission and neuronal excitability.
      alpha7 nAChRs are the second most prevalent nAChR subtype in the CNS following
      alpha4beta2. Serine 365 in the M3-M4 cytoplasmic loop of the alpha7 nAChR is a
      phosphorylation site for protein kinase A (PKA). D1/D5 dopamine receptors signal
      through the adenylate cyclase-PKA pathway and play a key role in working memory
      and attention in the prefrontal cortex. Thus, we examined whether the
      dopaminergic system, mediated through PKA, functionally interacts with the alpha7
      dependent cholinergic neurotransmission. In layer 1 interneurons of mouse
      prefrontal cortex, alpha7 nicotinic currents were decreased upon stimulation with
      8-Br-cAMP, a PKA activator. In HEK 293T cells, dominant negative PKA abolished 8
      Br-cAMP's effect of diminishing alpha7 nicotinic currents, while a constitutively
      active PKA catalytic subunit decreased alpha7 currents. In brain slices, the PKA
      inhibitor KT-5720 nullified 8-Br-cAMP's effect of attenuating alpha7 nicotinic
      responses, while applying a PKA catalytic subunit in the pipette solution
      decreased alpha7 currents. 8-Br-cAMP stimulation reduced surface expression of
      alpha7 nAChRs, but there was no change in single-channel conductance. The D1/D5
      dopamine receptor agonist SKF 83822 similarly attenuated alpha7 nicotinic
      currents from layer 1 interneurons and this attenuation of nicotinic current was
      prevented by KT-5720. These results demonstrate that dopamine receptor-mediated
      activation of PKA negatively modulates nicotinic neurotransmission in prefrontal
      cortical interneurons, which may be a contributing mechanism of dopamine
      modulation of cognitive behaviours such as attention or working memory.

PMID- 25990640
TI  - Transoral endoscopic-assisted styloidectomy: How should Eagle syndrome be managed
      surgically?
AB  - Eagle syndrome, or calcification of the stylohyoid ligament, is a rare condition
      that may present a clinical diagnostic dilemma for those unfamiliar with its
      existence and its typical presenting signs and symptoms. Management of this
      disease process may involve either non-surgical or surgical treatment options.
      When surgery is indicated, the choice of a specific surgical modality is highly
      variable and is generally dependent upon individual surgeon preference and
      experience, since the location of the styloid process is consistent between
      patients, and the required surgical access is also similar depending upon the
      specific surgical plan. This paper reports a case of Eagle syndrome managed with
      a transoral endoscopic-assisted approach, explores the advantages and
      disadvantages of each surgical approach, and reviews the literature regarding
      surgical management options for Eagle syndrome. 

PMID- 25990639
TI  - Submaximal exercise testing with near-infrared spectroscopy in Myalgic
      Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls:
      a case-control study.
AB  - BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a
      debilitating illness. Symptoms include profound fatigue and distinctive post
      exertional malaise (PEM). We asked whether a submaximal exercise test would prove
      useful for identifying different patterns of tissue oxygen utilization in
      individuals with ME/CFS versus healthy subjects. Such a test has potential to aid
      with ME/CFS diagnosis, or to characterize patients' illness. METHODS: A case
      control study of 16 patients with ME/CFS compared to 16 healthy controls
      completing a 3-min handgrip protocol was performed. Response was measured using
      near-infrared spectroscopy, resulting in measurements of oxygenated (O2Hb) and
      deoxygenated hemoglobin (HHb) over wrist extensors and flexors. Changes in O2Hb
      (delta (d)O2Hb) and HHb (dHHb) absorbance between the first and last contraction
      were calculated, as were the force-time product of all contractions, measured as
      tension-time index (TTI), and ratings of perceived exertion (RPE). RESULTS:
      Individuals with ME/CFS demonstrated smaller dO2Hb and dHHb than controls.
      However, after adjusting for TTI and change in total hemoglobin (delta (d)tHb),
      differences in dO2Hb and dHHb were reduced, with large overlapping variances. RPE
      was significantly higher for cases than controls, particularly at rest.
      CONCLUSIONS: Relative to controls, participants with ME/CFS demonstrated higher
      RPE, lower TTI, and reduced dO2Hb and dHHb during repetitive handgrip exercise,
      although considerable variance was observed. With further study, submaximal
      exercise testing may prove useful for stratifying patients with a lower
      propensity for inducing PEM, and have the ability to establish baseline
      intensities for exercise prescription.

PMID- 25990641
TI  - Life goals in patients with cancer: a systematic review of the literature.
AB  - OBJECTIVE: Purposes of this systematic review of life goal research in cancer
      patients were to (1) identify life goal characteristics and processes being
      examined, (2) describe instruments used to assess life goal constructs, (3)
      identify theoretical models being used to guide research, and (4) summarize what
      is known about the impact of the cancer experience on life goal characteristics,
      processes, and psychological outcomes. METHODS: We conducted this systematic
      review using MEDLINE, PubMed, CINAHL, and PsycINFO databases. Inclusion criteria
      were as follows: (1) published between 1993 and 2014, (2) English language, (3)
      cancer patient population, and (4) original research articles that assessed life
      goal characteristics and/or goal processes. One hundred ninety-seven articles
      were screened and 27 included in the final review. RESULTS: Seven life goal
      characteristics and seven life goal processes were identified, and less than half
      of studies investigated associations between goal characteristics and processes.
      Conceptual definitions were not provided for about half of the identified life
      goal constructs. Studies used both validated and author-developed instruments to
      assess goal constructs. Twenty-four different theoretical models were identified,
      with self-regulation theory most frequently cited. Overall, the literature
      suggests that cancer impacts patients' life goal characteristics and processes,
      and life goal disturbance is related to poorer psychological outcomes.
      CONCLUSIONS: The impact of the cancer experience on life goals is an important
      and emerging area of research that would benefit from conceptual and theoretical
      clarity and measurement consistency.

PMID- 25990643
TI  - Expression of peptide fragments from proADM and involvement of mitogen-activated
      protein kinase signaling pathways in pulmonary remodeling induced by high
      pulmonary blood flow.
AB  - Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized
      by progressive pulmonary arterial remodeling and right ventricular failure.
      Despite recent advances in pathophysiological mechanism exploration and new
      therapeutic approaches, PAH remains a challenging condition. In this study, we
      investigated the roles of the peptide fragments from proadrenomedullin (proADM)
      such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N
      terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary
      blood flow, and probed the possible involvement of mitogen-activated protein
      kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were
      artificially established by surgically connecting the left common carotid artery
      to the external jugular vein. We subcutaneously injected an extracellular signal
      regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated
      another eight rats with an equal volume of saline. Eight rats without connections
      served as the control group. We observed that mRNA expression levels of ADM,
      stress-activated protein kinase (SAPK), and ERK1/2 were significantly elevated in
      the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by
      PD98059. Protein levels of ADM, PAMP, p-SAPK, and p-ERK1/2 were significantly
      higher ADT was lower, and p-p38 remained unchanged in the rat models compared
      with the controls. However, the protein expression of both ADM and p-ERK1/2 was
      significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT,
      and PAMP respond to pulmonary remodeling, and that activation of the SAPK and
      ERK1/2 signaling pathways is involved in pulmonary hypertension and artery
      remodeling caused by high pulmonary blood flow. 

PMID- 25990644
TI  - Supramolecular fabrication of multilevel graphene-based gas sensors with high NO2
      sensibility.
AB  - This study reports the supramolecular assembly of a silver nanoparticle
      naphthalene-1-sulphonic acid-reduced graphene oxide composite (Ag-NA-rGO) and its
      utilization to fabricate a highly sensitive and selective gas sensor. The
      prepared supramolecular assembly acted not only as a non-covalent
      functionalization platform (pi-pi interaction) but was also an excellent scaffold
      to fabricate a highly sensitive and selective low concentration NO2 gas sensor.
      The prepared composites were characterized using several techniques, which
      revealed that the graphene sheets were dispersed as ultrathin monolayers with a
      uniform distribution of silver nanoparticles. The fabricated multilevel structure
      exhibited an excellent sensing performance, i.e. 2.8 times better, towards 10 ppm
      NO2 compared to the NA-rGO and rGO based sensors. Apart from its high
      sensitivity, superior reversibility and selectivity, the prepared supramolecular
      assembly exhibited an outstanding linear response over the large concentration
      range from 1 ppm to 10 ppm. The obtained results demonstrate that the prepared
      supramolecular assembly holds great potential in the fabrication of efficient and
      effective low-concentration NO2 gas sensors for practical applications. 

PMID- 25990642
TI  - Markers of renal disease and function are associated with systemic inflammation
      in HIV infection.
AB  - OBJECTIVES: Both renal disease and systemic inflammation predict non-AIDS
      defining events and overall mortality in HIV-infected patients. Here, we sought
      to determine the relationships between renal disease and circulating inflammation
      markers. METHODS: We performed a secondary analysis of AIDS Clinical Trials Group
      Study A5224s to determine if markers of renal disease [urine protein:creatinine
      ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular
      filtration rate (eGFR), using Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) creatinine and cystatin C-creatinine] were associated with markers of
      systemic inflammation [high-sensitivity C-reactive protein, interleukin-6, tumour
      necrosis factor (TNF)-alpha, soluble TNF-alpha receptor I (sTNFRI), sTNFRII, and
      soluble vascular cellular and intercellular adhesion molecules]. We correlated
      these renal and inflammatory markers prior to antiretroviral initiation and after
      96 weeks of therapy. RESULTS: We found that eGFR (estimated using CKD-EPI
      cystatin C-creatinine), uPCR, and uACR were significantly correlated with most
      assessed markers of systemic inflammation prior to antiretroviral initiation.
      uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained
      significantly correlated with most of the assessed inflammatory markers after 96
      weeks of antiretroviral therapy (ART). Most of these correlations, although
      statistically significant, were < 0.50. eGFR using CKD-EPI creatinine was much
      less frequently associated with inflammation markers and only significantly
      correlated with sTNFR1 at week 0 and with sTNFRI and II at week 96. CONCLUSIONS:
      Renal disease and function were associated with systemic inflammation in HIV
      infection, both before and after ART. Systemic inflammation may partially explain
      the relationships between proteinuria, albuminuria, and reduced renal function
      and future adverse outcomes.

PMID- 25990646
TI  - Amino acids flanking the central core of Cu,Zn superoxide dismutase are important
      in retaining enzyme activity after autoclaving.
AB  - Enzymes are known to be denatured upon boiling, although Cu,Zn superoxide
      dismutase of Potentilla atrosanguinea (Pot-SOD) retains significant catalytic
      activity even after autoclaving (heating at 121  degrees C at a pressure of 1.1
      kg per square cm for 20 min). The polypeptide backbone of Pot-SOD consists of 152
      amino acids with a central core spanning His45 to Cys145 that is involved in
      coordination of Cu(2+) and Zn(2+) ions. While the central core is essential for
      imparting catalytic activity and structural stability to the enzyme, the role of
      sequences flanking the central core was not understood. Experiments with deletion
      mutants showed that the amino acid sequences flanking the central core were
      important in retaining activity of Pot-SOD after autoclaving. Molecular dynamics
      simulations demonstrated the unfavorable structure of mutants due to increased
      size of binding pocket and enhanced negative charge on the electrostatic surface,
      resulting in unavailability of the substrate superoxide radical ([Formula: see
      text]) to the catalytic pocket. Deletion caused destabilization of structural
      elements and reduced solvent accessibility that further produced unfavorable
      structural geometry of the protein.

PMID- 25990647
TI  - Lattice-Directed Formation of Covalent and Organometallic Molecular Wires by
      Terminal Alkynes on Ag Surfaces.
AB  - Surface reactions of 2,5-diethynyl-1,4-bis(phenylethynyl)benzene on Ag(111),
      Ag(110), and Ag(100) were systematically explored and scrutinized by scanning
      tunneling microscopy, molecular mechanics simulations, and density functional
      theory calculations. On Ag(111), Glaser coupling reaction became dominant,
      yielding one-dimensional molecular wires formed by covalent bonds. On Ag(110) and
      Ag(100), however, the terminal alkynes reacted with surface metal atoms, leading
      to one-dimensional organometallic nanostructures. Detailed experimental and
      theoretical analyses revealed that such a lattice dependence of the terminal
      alkyne reaction at surfaces originated from the matching degree between the
      periodicities of the produced molecular wires and the substrate lattice
      structures. 

PMID- 25990645
TI  - High cardiometabolic risk in healthy Chilean adolescents: associations with
      anthropometric, biological and lifestyle factors.
AB  - OBJECTIVE: To analyse the prevalence of cardiovascular risk factors in healthy
      adolescents of low to middle socio-economic status and to study the influence of
      anthropometric, biological and lifestyle factors on the risk of metabolic
      syndrome (MetS). DESIGN: Cross-sectional study. BMI, waist circumference, blood
      pressure, fat and lean mass (by dual-energy X-ray absorptiometry), TAG, HDL
      cholesterol, glucose, insulin, homeostatic model assessment-insulin resistance
      index (HOMA-IR), food intake and physical activity were measured. Cardiovascular
      risk factors were defined using the International Diabetes Federation criteria
      and insulin resistance using HOMA-IR >=2.6. Bivariate and multivariate
      regressions examined the associations between MetS and anthropometric, biological
      and lifestyle factors. SETTING: Observational cohort study including Chilean
      adolescents, who were part of a follow-up study beginning in infancy. SUBJECTS:
      Adolescents aged 16-17 years (n 667). RESULTS: In the sample, 16.2% had obesity
      and 9.5% had MetS. Low HDL-cholesterol (69.9%), abdominal obesity (33.3%) and
      fasting hyperglycaemia (8.7%) were the most prevalent cardiovascular risk
      factors. In males, obesity (OR=3.7; 95% CI 1.2, 10.8), insulin resistance
      (OR=3.0; 95% CI 1.1, 8.2), physical inactivity (OR=2.9; 95% CI 1.1, 7.7) and
      sarcopenia (OR=21.2; 95% CI 4.2, 107.5) significantly increased the risk of MetS.
      In females, insulin resistance (OR=4.9; 95% CI 1.9, 12.6) and sarcopenia (OR=3.6;
      95% CI 1.1, 11.9) were significantly associated with MetS. CONCLUSIONS: High
      prevalences of obesity, abdominal obesity, dyslipidaemia, fasting hyperglycaemia
      and MetS were found in healthy adolescents. In both sexes, sarcopenia and insulin
      resistance were important risk factors of MetS. Promotion of active lifestyles at
      the school level and regulation of the sale of energy-dense foods are needed.

PMID- 25990648
TI  - Association of AT1R polymorphism with hypertension risk: An update meta-analysis
      based on 28,952 subjects.
AB  - BACKGROUND: Previous studies have shown that angiotensin II AT1 receptor gene
      (AT1R) polymorphisms are associated with the risk for hypertension. However, the
      results remain controversial. In the present study, we performed a meta-analysis
      to systematically summarize the association between AT1R genetic polymorphisms
      and the risk for hypertension. METHODS: We searched the literature in PubMed,
      EMBASE, ISI Web of Science, Wanfang, and Chinese National Knowledge
      Infrastructure databases (CNKI) to find case-control studies on the associations
      of AT1R genetic polymorphisms with the risk for hypertension. The meta-analysis
      was performed by using RevMan 5.0 software. The association of hypertension risk
      with AT1R genetic polymorphism was estimated by pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs). RESULTS: Fifty-six studies involving 28,952
      subjects were included in the present meta-analysis. Our results suggest that the
      polymorphism (A1166C) of AT1R gene is associated with a statistically increased
      hypertension risk, not only in Asian populations but also in Caucasian
      populations. We did not find any association in African populations. CONCLUSIONS:
      This meta-analysis suggests that A1166C polymorphism in the AT1R gene is
      associated with the risk of hypertension in Asian and Caucasian populations.

PMID- 25990649
TI  - The relationship between angiotensin-converting enzyme gene insertion/deletion
      polymorphism and digestive cancer risk: Insights from a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The gene encoding angiotensin-converting enzyme (ACE)
      has been implicated in the development of several malignancies. We aimed to meta
      analyze the association of ACE gene insertion/deletion (I/D) polymorphism with
      digestive cancer risk and seek possible sources of between-study heterogeneity.
      METHODS: Two authors independently assessed eligibility of each retrieved
      publication and gathered relevant data. Risk estimates were expressed as odds
      ratio (OR) and 95% confidence interval (CI). RESULTS: Sixteen publications were
      qualified for analysis, involving 2903 digestive cancer cases and 10,833
      controls. Overall analyses failed to show any significance for digestive cancer
      risk. There was moderate heterogeneity and lower publication bias for overall
      comparisons. In subgroup analyses, ACE gene II genotype was associated with a 15%
      reduced risk (OR=0.85, 95% CI: 0.57-1.27, p=0.434) for gastric cancer, but a 16%
      increased risk (OR=1.16, 95% CI: 0.89-1.52, p=0.273) for colorectal cancer. By
      source of controls, the I allele appeared to be a protective factor against
      digestive cancer in population-based studies (OR=0.87, 95% CI: 0.75-1.00,
      p=0.055) but a risk-conferring factor in hospital-based studies (OR=1.17, 95% CI:
      1.01-1.35, p=0.033). CONCLUSION: Our findings suggested that ACE gene I allele
      might be a protective factor against gastric cancer, necessitating further
      confirmation in large, population-based studies.

PMID- 25990650
TI  - The relationship between the polymorphisms of the CYP17A1 gene and hypertension:
      A meta-analysis.
AB  - OBJECTIVE: With the development of genome-wide association studies (GWAS)
      concerning hypertension, a growing number of susceptibility genes related to
      hypertension have been revealed. Subsequently, several studies have investigated
      the association between CYP17A1 rs1004467 heritable variation and hypertension;
      however, the results have been inconsistent. In this study, a meta-analysis was
      performed to assess the association between the CYP17A1 rs1004467 polymorphism
      and hypertension risk. METHODS: The PubMed, ISI Web of Science and Embase
      databases as well as China Wanfang, Weipu and the Chinese Journal Full-text
      Database were used to retrieve all publications from 2005 to 2013 related to case
      control studies that reported a link between the risk factors for hypertension
      and the CYP17A1 polymorphism. All association studies were identified, and a meta
      analysis was conducted using the RevMan 5.0 estimate for odds ratios (ORs) to
      determine whether the A allele predicts hypertension outcomes. RESULTS: Three
      articles including five studies (totaling 4495 patients and 3529 controls) were
      identified. The overall effect suggested that rs1004467 was significantly
      associated with hypertension (OR=1.22, 95%CI 1.08-1.38, p=0.001). CONCLUSIONS:
      The present meta-analysis confirmed the significant association between a
      polymorphism of the CYP17A1 gene and hypertension susceptibility. The CYP17A1 A
      allele should be considered a risk factor for hypertension.

PMID- 25990652
TI  - Accurate flexural spring constant calibration of colloid probe cantilevers using
      scanning laser Doppler vibrometry.
AB  - Calibration of the flexural spring constant for atomic force microscope (AFM)
      colloid probe cantilevers provides significant challenges. The presence of a
      large attached spherical added mass complicates many of the more common
      calibration techniques such as reference cantilever, Sader, and added mass. Even
      the most promising option, AFM thermal calibration, can encounter difficulties
      during the optical lever sensitivity measurement due to strong adhesion and
      friction between the sphere and a surface. This may cause buckling of the end of
      the cantilever and hysteresis in the approach-retract curves resulting in
      increased uncertainty in the calibration. Most recently, a laser Doppler
      vibrometry thermal method has been used to accurately calibrate the normal spring
      constant of a wide variety of tipped and tipless commercial cantilevers. This
      paper describes a variant of the technique, scanning laser Doppler vibrometry,
      optimized for colloid probe cantilevers and capable of spring constant
      calibration uncertainties near +/-1%. 

PMID- 25990651
TI  - Abnormalities in myo-inositol metabolism associated with type 2 diabetes in mice
      fed a high-fat diet: benefits of a dietary myo-inositol supplementation.
AB  - We previously reported that a chronic supplementation with myo-inositol (MI)
      improved insulin sensitivity and reduced fat accretion in mice. We then tested
      the potency of such dietary intervention in the prevention of insulin resistance
      in C57BL/6 male mouse fed a high-fat diet (HFD). In addition, some abnormalities
      in inositol metabolism were reported to be associated with insulin resistance in
      several animal and human studies. We then investigated the presence of such
      anomalies (i.e. inosituria and an inositol intra-tissue depletion) in this diet
      induced obesity (DIO) mouse model, as well as the potential benefit of a MI
      supplementation for inositol intra-tissue deficiency correction. HFD (60 % energy
      from fat) feeding was associated with inosituria and inositol intra-tissue
      depletion in the liver and kidneys. MI supplementation (0.58 mg/g per d) restored
      inositol pools in kidneys (partially) and liver (fully). HFD feeding for 4 months
      induced ectopic lipid redistribution to liver and muscles, fasting hyperglycaemia
      and hyperinsulinaemia, insulin resistance and obesity that were not prevented by
      MI supplementation, despite a significant improvement in insulin sensitivity
      parameter K insulin tolerance test and a reduction in white adipose tissue (WAT)
      mass ( - 17 %, P< 0.05). MI supplementation significantly reduced fatty acid
      synthase activity in epididymal WAT, which might explain its beneficial, but
      modest, effect on WAT accretion in HFD-fed mice. Finally, we found some
      abnormalities in inositol metabolism in association with a diabetic phenotype
      (i.e. insulin resistance and fasting hyperglycaemia) in a DIO mouse model.
      Dietary MI supplementation was efficient in the prevention of inositol intra
      tissue depletion, but did not prevent insulin resistance or obesity efficiently
      in this mouse model. 

PMID- 25990653
TI  - The potential of enzastaurin to enhance platelet aggregation and growth factor
      secretion: implications for cancer cell survival.
AB  - BACKGROUND: Enzastaurin is a protein kinase C (PKC)beta inhibitor with
      antiproliferative and proapoptotic effects that was in clinical development for
      the treatment of a variety of cancers. However, the primary endpoints in several
      clinical trials of enzastaurin were not met, and thrombosis was reported as an
      adverse effect in some trials. While investigating the role of PKC in regulating
      growth factor release from platelets, we found that, unlike other PKC inhibitors,
      enzastaurin may potentiate platelet aggregation. OBJECTIVE: To investigate the
      effects of enzastaurin on platelet aggregation, growth factor secretion from
      alpha-granules and cancer cell apoptosis in the presence of platelets. METHODS:
      Prostacyclin-washed platelets and platelet-rich plasma were isolated from the
      blood of healthy human volunteers. Platelet light-aggregometry was performed in
      the presence and absence of enzastaurin and acetylsalicylic acid (ASA). P
      selectin was measured by flow cytometry, and vascular endothelial growth factor
      (VEGF) release was measured by ELISA. A549 lung carcinoma cells were treated with
      releasates from enzastaurin-titrated platelets. A cell death ELISA was performed
      to measure A549 apoptosis. RESULTS AND CONCLUSIONS: Enzastaurin (10(-8) -10(-6) 
      m) potentiated aggregation of prostacyclin-washed platelets and caused an
      increase in VEGF release from alpha-granules that, in turn, promoted cancer cell
      survival. In platelet-rich plasma, 10(-6)  m enzastaurin inhibited platelet
      aggregation, but not 10(-7)  m enzastaurin, which also failed to suppress VEGF
      secretion. ASA abrogated enzastaurin-potentiated washed-platelet aggregation and
      VEGF release. These findings indicate that, at high plasma protein-free drug
      concentrations, enzastaurin potentiates platelet aggregation and growth factor
      secretion, an effect that may counteract its anticancer activity. ASA nullifies
      this effect.

PMID- 25990654
TI  - Descemet membrane endothelial keratoplasty.
AB  - Descemet membrane endothelial keratoplasty (DMEK) allows for selective
      replacement of damaged endothelial cells, using only donor Descemet's membrane
      with endothelium. However, early adoption by corneal surgeons has been limited
      (illustrated by graft registry reports: 0.7% all corneal transplants in the USA;
      0.4% in Australia for 2011) due to challenges in donor preparation and surgical
      technique. Recently, innovative donor preparation techniques may improve
      availability of pre-stripped DMEK donors from eye banks. The refinement of donor
      insertion and manipulation techniques has also improved outcomes and reduced
      graft detachment rates-still, the most common postoperative complication
      following DMEK. Randomised studies are needed to compare clinical practices and
      surgeon preferences, such as intraoperative use of long-acting gas, early versus
      late intervention of graft detachments and postoperative steroid management. A
      review of current literature reveals that most publications to date are reports
      from similar study cohorts by surgeons who pioneered and advocate this technique.
      Thus, more long-term clinical studies in other tertiary centres are required in
      order to confirm if the purported advantages of DMEK such as improved visual
      outcomes and reduced graft rejection are replicable among most corneal surgeons. 

PMID- 25990655
TI  - Achieving postoperative target range increases success of strabismus surgery in
      adults: a case for adjustable sutures?
AB  - BACKGROUND/AIMS: To evaluate the role of achieving immediate target angles on the
      success of strabismus surgery. METHODS: We performed a retrospective cohort study
      of all patients over 12 years old undergoing strabismus surgery with either
      adjustable or non-adjustable sutures. Target angle for patients with esotropia
      and vertical deviation was within 4 prism dioptres (PD) of orthotropia and for
      patients with exotropia between orthotropia and 8 PD of esotropia. Success was
      defined as alignment within 10 PD for horizontal rectus surgery and within 5 PD
      of orthotropia for vertical rectus surgery, without diplopia or reoperations. The
      main outcome measure was surgical success rate. RESULTS: Three hundred and fifty
      three patients were included in the study with mean follow-up of 13.9 (4-132)
      months. Patients achieving the target angle immediately postoperatively had
      higher success rate than patients who did not (83.6% vs 63.7%, p<0.0001, OR 2.9,
      95% CI 1.8 to 4.9). When target angle was achieved, adjustable and non-adjustable
      sutures had similar success (84.8% and 80.9%, respectively, p=0.46, OR 1.3, CI
      0.58 to 2.9). However, patients undergoing adjustable surgery were more likely to
      obtain the target angle (75.5% vs 54%, p<0.0001, OR 2.7, CI 1.7 to 4.2). Success
      for exotropia surgery was significantly higher when the immediate target angle
      was achieved (86.4% vs 58.7%, p<0.0001, OR 4.47, CI 2.3 to 8.6). For esotropia
      and vertical deviations, a similar beneficial effect was not shown (p=0.31, OR
      1.6, CI 0.65 to 4.0 and p=0.33, respectively). On multiple logistic regressions,
      sex, amblyopia, binocularity and reoperations were not significant factors in
      surgical success. CONCLUSIONS: Our results suggest that achieving the immediate
      target angle is the most significant factor in the success of strabismus surgery
      for exotropia. Adjustable suture surgery results in higher proportion of patients
      achieving this target angle.

PMID- 25990656
TI  - Junior doctors to ask lawyers if the NHS is in breach of human rights
      legislation.

PMID- 25990657
TI  - The Impact of IFN-gamma Gene Polymorphisms on Spontaneous Clearance of HCV
      Infection in Fars Province, Southern of Iran.
AB  - BACKGROUND: Certain polymorphisms in cytokine genes such as IFN-gamma may
      influence the outcome of hepatitis C virus (HCV) infection. Here the frequency of
      the genotype, allele, and haplotype of IFN-gamma gene at some loci is
      investigated in HCV-infected patients. METHODS: Totally 255 patients with chronic
      HCV infection and 44 spontaneously cleared individuals were included. The chronic
      or clearance states were confirmed using enzyme-linked immunosorbent assay
      (ELISA) and two different qualitative reverse transcriptase polymerase chain
      reaction (RT-PCR) techniques. IFN-gamma gene polymorphisms were performed by PCR
      using sequence-specific primers and PCR-RLFP on extracted genomic DNA. RESULTS:
      The frequency of GG genotype (P = 0.0001, OR: 5.69 and CI: 2.21-14.62) and allele
      (P = 0.0003, OR: 2.73 and CI: 1.54-4.83) of IFN-gamma gene at +2109 locus was
      significantly higher in cases that spontaneously cleared the infection. Haplotype
      analysis showed the association of AG haplotype (P = 0.0046, OR = 6.14 and CI =
      1.56-25) with spontaneous clearance of the infection. CONCLUSION: Our finding
      indicated that individuals with GG genotype at +2109 loci of IFN-gamma gene and
      also AG haplotype (A allele at +874 loci and G allele at +2109 loci) may clear
      HCV infection more frequently than those with AA and AG genotype at +2109 loci
      and AA, TA, and TG haplotype.

PMID- 25990658
TI  - Modulation of the attentional span by foveal and parafoveal task load: An ERP
      study using attentional probes.
AB  - Due to capacity limitation, visual attention must be focused to a limited region
      of the visual field. Nevertheless, it is assumed that the size of that region may
      vary with task demands. We aimed to obtain direct evidence for the modulation of
      visuospatial attention as a function of foveal and parafoveal task load.
      Participants were required to fixate the center word of word triplets. In
      separate task blocks, either just the fixated word or both the fixated and the
      parafoveal word to the right should be semantically classified. The
      spatiotemporal distribution of attention was assessed with task-irrelevant probes
      flashed briefly at center or parafoveal positions, during or in between word
      presentation trials. The N1 component of the ERP elicited by intertrial probes at
      possible target positions increased with task demands within a block. These
      results suggest the recruitment of additional attentional resources rather than a
      redistribution of a fixed resource pool, which persists across trials. 

PMID- 25990660
TI  - Controlling the thermoelectric properties of polymers: application to PEDOT and
      polypyrrole.
AB  - Poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy) films have been
      prepared by an electrochemical method in a three electrode cell. The films have
      been obtained at different oxidation levels regarded as bipolaron, polaron and
      neutral states by varying the voltage, as is usually done in conjugated
      heterocyclic polymers. The voltage (-0.2 < V < 1.0 V) has been applied versus a
      Ag/AgCl reference electrode, producing a variation of one order of magnitude in
      the electrical conductivity and the Seebeck coefficient of the films. In the
      voltage range explored, the electrical conductivity increases from 80 to 766 S
      cm(-1) in PEDOT and from 15 to 160 S cm(-1) in PPy, while the Seebeck coefficient
      decreases from 37.0 to 9.6 MUV K(-1) for PEDOT and from 51.0 to 6.7 MUV K(-1) for
      PPy. The thermal conductivity remains unchanged with the oxidation state of the
      film, kappa ~ 0.35 +/- 0.02 W m(-1) K(-1) for PEDOT and 0.17 +/- 0.02 W m(-1) K(
      1) for PPy. A maximum thermoelectric efficiency of 1.4 * 10(-2) for PEDOT and 6.8
      * 10(-3) for PPy has been achieved. These changes are related to the doping level
      of the polymer films and they can be accurately controlled by the applied
      voltage. In this work, we provide a very simple method to control and optimize
      the power factor or the figure of merit of conducting polymers. 

PMID- 25990659
TI  - Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in
      patients with advanced cancers metastatic to the liver.
AB  - BACKGROUND: Liver metastases are associated with a poor prognosis. We
      investigated the use of hepatic arterial infusion (HAI) of irinotecan combination
      therapy in patients with liver metastases. PATIENTS AND METHODS: Patients with
      histologically confirmed advanced cancer with liver metastases that was
      refractory to standard therapy were eligible. A standard "3 + 3" phase I study
      design was used to determine the dose-limiting toxicity (DLT) and the maximum
      tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with
      systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or
      (c) bevacizumab and cetuximab. RESULTS: From October 2009 through December 2013,
      98 patients with various tumor types were enrolled (median age, 62 years, range,
      34-85; and median number of prior therapies, 4, range, 1-11). In cohorts A and C,
      dose escalation continued until the highest dose level-considered the MTD-was
      reached. In cohort B, dose escalation continued until dose level 3, and dose
      level 2 was considered the MTD. Rates of grade 3/4 adverse events were as
      follows: diarrhea, 8 %; fatigue, 4 %; neutropenia, 4 %; thrombocytopenia, 2 %;
      and skin rash, 2 %. Seventy-seven patients were evaluable for response. Partial
      response was noted in 5 (6.5 %) patients (neuroendocrine cancer, n = 2; CRC, n =
      2; NSCLC, n = 1); and stable disease >= 6 months in 17 (22.1 %) patients (CRC, n
      = 13; breast, n = 1; neuroendocrine, n = 1; NSCLC, n = 1; pancreatic, n = 1).
      CONCLUSIONS: HAI irinotecan in combination with bevacizumab; oxaliplatin plus
      bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option
      for selected patients with advanced cancer and liver involvement.

PMID- 25990662
TI  - Pulmonary drug and vaccine delivery: therapeutic significance and major
      challenges.

PMID- 25990661
TI  - Dual antiplatelet therapy in acute ischemic stroke.
AB  - Stroke recurrence is common in the early period after a cerebral ischemic event.
      Treatment with an antiplatelet agent is recommended to reduce recurrent stroke
      and death in patients with a non-cardioembolic ischemic stroke and transient
      ischemic attack. Compared to monotherapy, dual antiplatelet therapy has more
      robust inhibition of platelet activation but a higher risk of systemic bleeding
      and intracranial hemorrhage. Randomized controlled trials and meta-analyses
      suggest that short-term use of dual antiplatelet treatment initiated early after
      ischemic stroke and TIA reduces the risk of recurrent stroke and major vascular
      events without significantly increasing the hemorrhagic complication rates,
      particularly in those with large-vessel disease, while long-term dual
      antiplatelet treatment increases the risk of systemic and intracranial hemorrhage
      over time, offsetting any potential benefit. Until further data becomes
      available, clinicians should carefully assess this risk and benefit in each case
      and continually reevaluate the need for prolonged dual antiplatelet therapy. 

PMID- 25990664
TI  - Decreased hemoglobin levels, cerebral small-vessel disease, and cortical atrophy:
      among cognitively normal elderly women and men.
AB  - BACKGROUND: Decreased hemoglobin levels increase the risk of developing dementia
      among the elderly. However, the underlying mechanisms that link decreased
      hemoglobin levels to incident dementia still remain unclear, possibly due to the
      fact that few studies have reported on the relationship between low hemoglobin
      levels and neuroimaging markers. We, therefore, investigated the relationships
      between decreased hemoglobin levels, cerebral small-vessel disease (CSVD), and
      cortical atrophy in cognitively healthy women and men. METHODS: Cognitively
      normal women (n = 1,022) and men (n = 1,018) who underwent medical check-ups and
      magnetic resonance imaging (MRI) were enrolled at a health promotion center. We
      measured hemoglobin levels, white matter hyperintensities (WMH) scales, lacunes,
      and microbleeds. Cortical thickness was automatically measured using surface
      based methods. Multivariate regression analyses were performed after controlling
      for possible confounders. RESULTS: Decreased hemoglobin levels were not
      associated with the presence of WMH, lacunes, or microbleeds in women and men.
      Among women, decreased hemoglobin levels were associated with decreased cortical
      thickness in the frontal (Estimates, 95% confidence interval, -0.007, (-0.013, 
      0.001)), temporal (-0.010, (-0.018, -0.002)), parietal (-0.009, (-0.015, 
      0.003)), and occipital regions (-0.011, (-0.019, -0.003)). Among men, however, no
      associations were observed between hemoglobin levels and cortical thickness.
      CONCLUSION: Our findings suggested that decreased hemoglobin levels affected
      cortical atrophy, but not increased CSVD, among women, although the association
      is modest. Given the paucity of modifiable risk factors for age-related cognitive
      decline, our results have important public health implications.

PMID- 25990665
TI  - Horizontal and vertical targeting: a population-based comparison of public
      eldercare services in urban and rural areas of Sweden.
AB  - The concepts of target efficiency can be used to assess the extent to which
      service provision is in line with the needs of the population. Horizontal target
      efficiency denotes the extent to which those deemed to need a service receive it
      and vertical target efficiency is the corresponding extent to which those who
      receive services actually need them. The aim of this study was to assess the
      target efficiency of the Swedish eldercare system and to establish whether target
      efficiencies differ in different geographical areas such as large urban, midsize
      urban and rural areas. Vertical efficiency was measured by studying those people
      who received eldercare services and was expressed as a percentage of those who
      received services who were functionally dependent. To measure horizontal target
      efficiency, data collected at baseline in the longitudinal population study SNAC
      (Swedish National study on Aging and Care) during the years 2001-2004 were used.
      The horizontal efficiency was calculated as the percentage of functionally
      dependent persons who received services. Functional dependency was measured as
      having difficulty with instrumental activities of daily living (IADL) and/or
      personal activities of daily living (PADL). Services included long-term municipal
      eldercare services (LTC). Horizontal target efficiency for the public LTC system
      was reasonably high in all three geographical areas, when using dependency in
      PADL as the measure of need (70-90 %), but efficiency was lower when the less
      restrictive measure of IADL dependency was used (40-50 %). In both cases, the
      target efficiency was markedly higher in the large urban and the rural areas than
      in the midsize urban areas. Vertical target efficiency showed the same pattern-it
      was almost 100 % in all areas for IADL dependency, but only 50-60 % for PADL
      dependency. Household composition differed in the areas studied as did the way
      public long-term care was provided to people living alone as compared to those co
      habiting. 

PMID- 25990666
TI  - The learning curve in robotic distal pancreatectomy.
AB  - No data are available on the learning curve in robotic distal pancreatectomy
      (RADP). The learning curve in RADP was assessed in 55 consecutive patients using
      the cumulative sum method, based on operative time. Data were extracted from a
      prospectively maintained database and analyzed retrospectively considering all
      events occurring within 90 days of surgery. No operation was converted to
      laparoscopic or open surgery and no patient died. Post-operative complications
      occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients
      (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C
      pancreatic fistula occurred. Four patients received blood transfusions (7.2%),
      three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the
      reduction of operative times (421.1 +/- 20.5 vs 248.9 +/- 9.3 min; p < 0.0001),
      completion of the learning curve was achieved after ten operations. Operative
      time of the first 10 operations was associated with a positive slope (0.47 +
      1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45
      procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p <
      0.0001*). After completion of the learning curve, more patients had a malignant
      histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields
      (11.1 +/- 12.2 vs 20.9 +/- 18.5) (p = 0.04) and lower rate of spleen preservation
      (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the
      learning curve was completed after ten operations. Improvement in clinical
      outcome was not demonstrated, probably because of the limited occurrence of
      outcome comparators.

PMID- 25990667
TI  - Cardiovascular diseases after liver transplantation--a still emerging and
      unsolved problem!

PMID- 25990668
TI  - Association study of the miRNA-binding site polymorphisms of CDKN2A/B genes with
      gestational diabetes mellitus susceptibility.
AB  - AIMS: Gestational diabetes mellitus (GDM) is a complex disease induced by a
      combination of genetic factors and environmental exposures. Growing evidence
      suggests that common single nucleotide polymorphisms within miRNA-binding sites
      (miR-binding SNPs) contribute to the development of various diseases. However,
      the roles of miR-binding SNPs in GDM have not been fully elucidated. The CDKN2A/B
      genes have been identified as two of the strongest genetic determinants for
      diabetes risk. The aim of the study was to first investigate the associations
      between miR-binding SNPs of CDKN2A/B, GDM susceptibility, and quantitative
      metabolism traits. METHODS: Three miR-binding SNPs of CDKN2A/B gene (rs1063192,
      rs3217992, and rs3088440) were selected and genotyped using TaqMan allelic
      discrimination assays in 839 cases of GDM and 900 controls. RESULTS: The CC
      genotype of CDKN2B rs1063192, which is located in the hsa-miR-323b-5p binding
      site, was significantly associated with GDM [OR 1.418 (1.143, 1.908); p = 0.003].
      The C allele of rs1063192 occurred with significantly higher frequency in GDM [OR
      1.22 (1.03, 1.44); p = 0.021]. The rs1063192 genotype CC exhibited increased
      glucose levels at 1 h and 3 h, as well as higher insulin levels at 3 h during an
      OGTT compared with the control TT genotype (p < 0.05). We also found that the
      rs1063192 CC genotype was associated with lower total cholesterol and LDL
      cholesterol levels (p < 0.05). CONCLUSIONS: The CC genotype of CDKN2B rs1063192
      in the hsa-miR-323b-5p binding site increased the risk of GDM in pregnant Chinese
      Han women. Importantly, our study provides evidence that miR-binding SNPs are a
      novel source of GDM susceptibility loci.

PMID- 25990669
TI  - The advent of biosimilars for the treatment of diabetes: current status and
      future directions.
AB  - Biosimilar insulins are likely to enter the market of diabetes therapies as
      patents for major branded insulin products start to expire in the next few years
      (on June 2014, the European Medicines Agency authorized the first biosimilar of
      insulin glargine, Abasria, 100 Units/ml, for the treatment of diabetes mellitus).
      This would allow providing comparable clinical benefits of the current available
      insulins at a significantly lower cost, thus increasing the affordability and
      access of insulin treatment for patients with diabetes. Biosimilars are approved
      via a stringent regulatory pathway demonstrating quality, safety, and efficacy
      comparable to the reference product. However, the production complexities of such
      products raise important considerations for treatment efficacy and patient
      safety, including naming and product tracking, substitution practices, and
      pharmacovigilance. Additionally, as practitioners' knowledge regarding the
      differences about pharmacological, clinical, and regulatory aspects between
      biosimilars and generic small molecules is often suboptimal, specific education
      on biosimilar prescribing, dispensing, and administering is critical for ensuring
      patients' benefit and safety. This article discusses all the issues concerning
      biosimilar, especially biosimilar insulins. 

PMID- 25990670
TI  - Single-stage bilateral thoracic surgery via a combined VATS and open approach for
      left central bronchogenic carcinoma with carinal invasion: report of two cases.
AB  - BACKGROUND: Surgery for patients with left central bronchogenic carcinoma
      invading the carina is challenging due to the complexity of left sleeve
      pneumonectomy, carinal resection, and airway reconstruction and management. Here
      we describe a modified approach to overcome this problem. CASE PRESENTATION:
      Between March 2011 and September 2012, two patients with left central
      bronchogenic carcinoma invading the carina underwent single-stage bilateral
      thoracic surgery via a combined approach incorporating video-assisted thoracic
      surgery (VATS) and thoracotomy in our hospital. We reviewed our experience with
      this type of surgery and analyze its outcomes. CONCLUSIONS: Single-stage,
      bilateral thoracic surgery incorporating video assisted thoracic surgery (VATS)
      and thoracotomy provides optimal exposure of the operative field, reduces
      surgical trauma, and ensures the integrity of tumor excision and exactness of
      tracheobronchial anastomosis. This may be a safe and feasible alternative for
      left carinal pneumonectomy.

PMID- 25990671
TI  - Pd-catalyzed cascade cyclization by intramolecular Heck insertion of an allene
      allylic amination sequence: application to the synthesis of 3,4-fused tricyclic
      indoles.
AB  - A novel Pd-catalyzed cascade cyclization by intramolecular Heck insertion of an
      allene-allylic amination sequence was developed. Allenes tethered to ortho
      iodoaniline derivatives at the meta-position were reacted with 5-10 mol % of Pd
      catalyst and 4 equiv of K2CO3 in DMSO at 90  degrees C, producing 3,4-fused
      tricyclic 3-alkylidene indoline derivatives in moderate to excellent yield. The
      reaction products were divergently transformed into three types of 3,4-fused
      tricyclic indole derivatives, successfully demonstrating the versatile properties
      of the reaction products. 

PMID- 25990672
TI  - The Expression of Genetic Risk for Aggressive and Non-aggressive Antisocial
      Behavior is Moderated by Peer Group Norms.
AB  - Numerous studies have shown that aggressive and non-aggressive antisocial
      behaviors are important precursors of later adjustment problems. There is also
      strong empirical evidence that both types of antisocial behavior are partially
      influenced by genetic factors. However, despite its important theoretical and
      practical implications, no study has examined the question whether environmental
      factors differentially moderate the expression of genetic influences on the two
      types of antisocial behavior. Using a genetically informed design based on 266
      monozygotic and dizygotic twin pairs, this study examined whether the expression
      of genetic risk for aggressive and non-aggressive antisocial behavior varies
      depending on the peer group's injunctive norms (i.e., the degree of
      acceptability) of each type of antisocial behavior. Self-reported aggressive and
      non-aggressive antisocial behavior and classroom-based sociometric nominations
      were collected when participants were 10 years old. Multivariate genetic analyses
      revealed some common genetic factors influencing both types of antisocial
      behavior (i.e., general antisocial behavior) as well as genetic influences
      specific to non-aggressive antisocial behavior. However, genetic influences on
      general antisocial behavior, as well as specific genetic influences on non
      aggressive antisocial behavior, vary depending on the injunctive classroom norms
      regarding these behaviors. These findings speak to the power of peer group norms
      in shaping aggressive and non-aggressive antisocial behavior. They also
      contribute further to understanding the distinctive development of both types of
      antisocial behavior. Finally, they may have important implications for prevention
      purposes. 

PMID- 25990674
TI  - Foreign materials found in the cardiovascular system after instrumentation or
      surgery (Including a guide to their light microscopic identification).
AB  - Foreign materials are often seen by light microscopy in surgical or autopsy
      specimens sent from the cardiovascular clinical services. This paper describes
      the range of materials that may be recovered in such specimens and provides a
      pictorial guide to aid in their identification. The spectrum of medical and
      nonmedical foreign materials that may be encountered in the cardiovascular system
      is discussed. 

PMID- 25990675
TI  - Pathologic analysis of 34 explanted symbion ventricular assist devices and 10
      explanted Jarvik-7 total artificial hearts.
AB  - Thirty-four Symbion ventricular assist devices and 10 Jarvik-7 total artificial
      hearts that had been in clinical use for 1 to 164 days (assist devices) and 1 to
      176 days (artificial hearts) were analyzed using a detailed protocol for
      pathological analysis. The major finding was thrombus formation in 85% of the
      assist devices and 75% of the artificial hearts. Thrombi were generally small and
      in only one case interfered with pump function. The number of distinct thrombi
      per device was 2.5 mean (range 0-5) for assist devices and 2.6 mean (range 0-6)
      for artificial hearts. Major sites of thrombus formation in the assist devices
      were valves, valve connections, diaphragm, and the inner surface of the deairing
      port. Artificial heart thrombi were predominantly paravalvular. In order to
      relate sites of diaphragmatic thrombi to specific design features of the assist
      device, the pattern was analyzed quantitatively using a polar coordinate mapping
      technique to measure the average radial thrombus length around the circumference
      of each diaphragm. The concentration of thrombus was highest between the valve
      orifices and lateral to the outflow valve. This identified areas particularly
      susceptible to thrombus formation and thereby targets specific pump features for
      redesign. Intraluminal infection was seen in 1 assist device and 1 artificial
      heart (outflow grafts); extraluminal infection was seen in two artificial hearts
      (infected hematomas around the outflow grafts). Neither device mineralization for
      mechanical defects were noted. Thus thrombus formation related to (and potential
      thromboemboli from) valves, their connectors, and the pumping diaphragms
      represents the major device-associated complication of pneumatic Symbion assist
      devices and Jarvik-7 artificial hearts. Thrombi associated with other sites and
      both intra- and extraluminal infection occur less frequently. 

PMID- 25990673
TI  - Predicting Depressive Symptoms and Weight from Adolescence to Adulthood:
      Stressors and the Role of Protective Factors.
AB  - Depressive symptoms and weight gain follow similar developmental trajectories
      from adolescence to adulthood and stressors are a risk factor for both. However,
      less is known about whether they share protective factors that reduce the risk
      for depressive symptoms and weight gain. The goal of the current study was to
      examine the role of stress and four protective factors (social support, self
      esteem, physical activity, and sedentary behavior) as predictors of depressive
      symptoms and body mass index over time. Participating in the current study were
      6504 (51.6 % female; 60.7 % European American, 22.5 % African American, 11.4 %
      Hispanic, 3.3 % Asian American, and 2 % other ethnicities) adolescents from the
      National Study of Adolescent and Adult Health. Participants were followed for
      three waves from adolescence to young adulthood (Wave I age range = 12-18; Wave
      III age range = 18-26). Data were analyzed using multi-level modeling and results
      showed that stressors significantly predicted trajectories of depressive symptoms
      and body mass index over time. Social support buffered the effects of stressors
      on BMI over time. Self-esteem influenced trajectories of both BMI and depressive
      symptoms. Differential effects were found for physical activity with physical
      activity predicting declines in depressive symptoms and sedentary behavior
      predicting declines in BMI over time. The current study suggests that stress is a
      common risk factor for depressive symptoms and weight gain, but that there is
      specificity in how the protective factors influence each type of outcome. 

PMID- 25990676
TI  - Molecular and cellular mechanisms of induction and regression of cardiac fibrosis
      in various models of myocardial hypertrophy.
AB  - This review is the summary of our findings on collagen gene expression and
      regulation in ventricular myocardium in experimental animal models of cardiac
      hypertrophy and in cardiac fibroblasts in response to hormonal stimuli. Cardiac
      fibrosis, or accumulation of collagen in the myocardium, is seen in several
      models of cardiac hypertrophy, such as those induced by aging, pressure overload,
      and norepinephrine-induced hypertension. Results on collagen gene expression have
      indicated that initial up-regulation of collagen gene expression usually precedes
      collagen accumulation in hypertrophied heart in those models. Thyroid hormone
      induced cardiac hypertrophy, however, is distinguished from those types of
      hypertrophy by the absence of fibrosis and by down-regulation of collagen gene
      expression in ventricular tissue. Our in vitro studies on cardiac fibroblasts
      indicate that absence of fibrosis in thyroid hormone-induced hypertrophy could be
      the result of an inhibitory effect of thyroid hormone on collagen gene expression
      at transcriptional levels. Thyroid hormone was also shown to cause regression of
      cardiac fibrosis in the heart of a genetic model of collagen overproduction, the
      tight skin (TSK) mouse. These findings indicate that cardiac fibrosis and cardiac
      hypertrophy are induced via different mechanisms and that presence of cardiac
      hypertrophy does not imply cardiac fibrosis. The findings on inhibitory effects
      of thyroid hormone on collagen gene expression further suggest that biological
      inhibitory pathways, such as hormonal regulation, could be activated to
      compensate for excessive collagen production or for diminished collagen
      degradation by cardiac fibroblasts in cases of predisposition to cardiac
      fibrosis. 

PMID- 25990677
TI  - Myofibroblasts and smooth muscle cells in human myocardial scars: Possible
      origins and inductive factors.
AB  - Necrotic myocardial lesions, including myocardial infarcts, heal by formation of
      scar tissue, and it is commonly thought that fibroblasts are the principal cells
      producing and maintaining the scar tissue matrix. In contrast to this notion, our
      study of old myocardial scars in 11 human hearts revealed that myofibroblasts
      (MFBs) and nonvascular smooth muscle cells (SMCs) were the dominant cell types.
      Both contractile cell types stained positively with antibody to alpha-smooth
      muscle actin and were identified ultrastructurally by the presence of
      nonsarcomeric myofibrillar elements. They were distinguished from each other by
      basal lamina, which invested the SMCs but not the MFBs. Neither cell type was
      identified in the myocardium of 3 normal human hearts, where fibroblasts were the
      normal interstitial cells. In earlier studies, we made similar observations in
      rat heart scars. The presence of MFBs and SMCs in myocardial scar tissue but not
      in normal myocardium raises questions about their origins, lineage relationships,
      inductive mechanisms, and functions. The results of our studies indicated that
      the MFB and SMC phenotypes were induced and maintained by the cyclical physical
      forces associated with myocardial contractions; that fibroblasts and MFBs seemed
      to be phenotypic modulations of the same cell type in a physical environment
      favoring expression of the MFB form; that the nonvascular SMCs were not derived
      from MFBs but may have come from cells located in vessel walls; and that the
      contractile cells in scar tissue might resist and counteract the stretching
      forces induced by myocardial contractions. 

PMID- 25990678
TI  - The cardiovascular pathologist: A pathologist awaiting better definition.

PMID- 25990679
TI  - Staphylococcus aureus versus Streptococcus pyogenes in hand infection.

PMID- 25990680
TI  - Mode of delivery and cranial bleeding in newborns with haemophilia: a systematic
      review and meta-analysis of the literature.
AB  - OBJECTIVES: Cranial bleeding at birth can result in significant neurological
      morbidity in newborns with haemophilia. The optimum mode of delivery (MOD) of a
      potentially affected foetus remains controversial. AIM: The aim of this review is
      to ascertain overall incidence of cranial bleeding in newborns with haemophilia
      compared to the general population and the impact of MOD on rates of intracranial
      haemorrhage (ICH). METHOD: An EMBASE/MEDLINE search using key terms revealed the
      relevant studies. Studies included report the incidence of cranial bleeding by
      MOD within a newborn population. The heterogenicity across studies was assessed
      using Cochrane's Q test and I(2) statistic and studies were assigned appropriate
      weight based on a fixed-effect model. Odds ratio (OR) is the primary effect
      measure. RESULTS: Newborns with haemophilia are 44 times (95% CI: 34.7-57.1, P <
      0.01) more likely to experience symptomatic ICH, and 8 times (95% CI: 5.38-12.6,
      P < 0.01) more likely to experience extracranial haemorrhage at birth, compared
      to the general population. In newborns with haemophilia the OR of experiencing
      ICH are 4.4 (95% CI: 1.46-13.7, P = 0.008) following an assisted vaginal delivery
      (AVD) and 0.34 (95% CI: 0.14-0.83, P = 0.018) following caesarean section (CS),
      compared to vaginal delivery. CONCLUSION: Cranial bleeding occurs with a
      significantly higher frequency in newborns with haemophilia compared to the
      general population. In newborns with haemophilia, delivery by a CS is associated
      with the lowest risk of ICH. AVD significantly increases the risk of ICH and
      should be avoided.

PMID- 25990681
TI  - Recent applications of carbon nanomaterials in fluorescence biosensing and
      bioimaging.
AB  - Carbon-based nanomaterials as important agents for biological applications have
      emerged in the past few years due to their unique optical, electronic,
      mechanical, and chemical properties. Many of these applications rely on
      successful surface modifications. This review article comprises two main parts.
      In the first part, we briefly review the properties and surface modifications of
      several classes of carbon nanomaterials, mainly carbon nanotubes (CNTs), graphene
      and its derivatives, carbon dots (CDs) and graphene quantum dots (GQDs), as well
      as some other forms of carbon-based nanomaterials such as fullerene, carbon
      nanohorns (CNHs) and carbon nanoonions (CNOs). In the second part, we focus on
      the biological applications of these carbon nanomaterials, in particular their
      applications for fluorescence biosensing as well as bioimaging. 

PMID- 25990682
TI  - Exploiting Large-Pore Metal-Organic Frameworks for Separations through Entropic
      Molecular Mechanisms.
AB  - We review the molecular mechanisms behind adsorption and the separations of
      mixtures in metal-organic frameworks and zeolites. Separation mechanisms can be
      based on differences in the affinity of the adsorbate with the framework and on
      entropic effects. To develop next-generation adsorbents, the separation
      efficiency of the materials needs to be improved. The performance under
      industrially relevant conditions largely depends on two factors: 1) the
      separation selectivity and 2) the pore volume capacity of the material. Enthalpic
      mechanisms can lead to increased selectivities, but these are mostly restricted
      to the low loading regime, and hence these mechanisms are unable to make use of
      all of the large-pore volume that a metal-organic framework can provide.
      Industrial processes routinely operate in the pore saturation regime. In this
      Review, we focus on entropic molecular separation mechanisms that are effective
      under these conditions and, in particular, on a recent methodology to obtain high
      selectivities at high pore loading. 

PMID- 25990683
TI  - Early Detection of Bi-ventricular and Atrial Mechanical Dysfunction Using Two
      Dimensional Speckle Tracking Echocardiography in Patients with Sarcoidosis.
AB  - PURPOSE: Sarcoidosis is a systemic inflammatory disease with unknown etiology
      involving several organs. Myocardial involvement, pericarditis, severe rhythm
      abnormalities, and heart valve disease due to papillary muscle dysfunction are
      some of the cardiac manifestations. Conventional echocardiographic methods remain
      insufficient for the determination of subclinical myocardial dysfunction in
      patients with sarcoidosis. In our study, we investigated the impact of
      sarcoidosis on bi-ventricular and atrial functions using two-dimensional (2D)
      speckle tracking echocardiography (STE). METHODS: Forty patients with sarcoidosis
      and 20 age and sex-matched controls were recruited into study. All subjects
      underwent a transthoracic echocardiography for the evaluation of ventricular and
      atrial functions with 2D STE. RESULTS: Left ventricular (LV) dimensions, LV
      ejection fraction, and right ventricular (RV) systolic velocity were similar
      between the two groups. Left atrial (LA) diameter was significantly higher in
      sarcoidosis patients than controls. Eighteen (45%) patients in the sarcoidosis
      group and 1 (5%) patient in the control group had LV diastolic dysfunction. LV
      global longitudinal, radial, circumferential strain, twist, untwists, and RV
      global longitudinal strain values were significantly lower in sarcoidosis
      patients compared to controls. LA and RA reservoir functions were also
      significantly lower in sarcoidosis patients than controls. CONCLUSION: Although
      impaired LV diastolic function was detected using conventional parameters, only
      novel advanced echocardiographic modalities demonstrated impaired bi-ventricular
      and atrial mechanical functions in patients with sarcoidosis.

PMID- 25990684
TI  - G-quadruplex induced chirality of methylazacalix[6]pyridine via unprecedented
      binding stoichiometry: en route to multiplex controlled molecular switch.
AB  - Nucleic acid based molecular device is a developing research field which attracts
      great interests in material for building machinelike nanodevices. G-quadruplex,
      as a new type of DNA secondary structures, can be harnessed to construct
      molecular device owing to its rich structural polymorphism. Herein, we developed
      a switching system based on G-quadruplexes and methylazacalix[6]pyridine (MACP6).
      The induced circular dichroism (CD) signal of MACP6 was used to monitor the
      switch controlled by temperature or pH value. Furthermore, the CD titration, Job
      plot, variable temperature CD and (1)H-NMR experiments not only confirmed the
      binding mode between MACP6 and G-quadruplex, but also explained the difference
      switching effect of MACP6 and various G-quadruplexes. The established strategy
      has the potential to be used as the chiral probe for specific G-quadruplex
      recognition. 

PMID- 25990685
TI  - Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three
      patients.
AB  - AIM: Osteoarthritis is a degenerative joint disease characterized by the
      destruction of joint cartilage. Mesenchymal stem cells (MSCs) are found in low
      numbers in normal cartilage, mainly in the superficial layer, acting as repairing
      agents. In OA, MSCs are seen in larger numbers, but act chaotic and are unable to
      repair the cartilage. The synovial membrane becomes inflamed and interacts with
      the cartilage. Transplanted MSC have the ability to normalize them, redirecting
      them to their normal function. In a preliminary study, we showed that MSC could
      improve knee OA in four patients at 6 months. This report shows their long-term
      follow-up at 5 years. METHODS: One patient was lost to follow-up at 2 years and
      three were followed for 5 years. They were aged 55, 57, 65 and 54 years, and had
      moderate to severe knee osteoarthritis. The worse knee of each patient was
      injected with 8-9 * 10(6) MSC. RESULTS: As previously reported, all parameters
      improved in transplant knees at 6 months (walking time, stair climbing, gelling
      pain, patella crepitus, flection contracture and the visual analogue score on
      pain). Then, they started gradually to deteriorate, but at 5 years they were
      still better than at baseline. PGA (Patient Global Assessment) improved from
      baseline to 5 years. The better knee at baseline (no MSC), continued its
      progression toward aggravation and at 5 years became the worse knee. CONCLUSION:
      Transplant knees were all in a rather advanced stage of OA. Earlier
      transplantation may give better results in long-term follow-up. This is what
      future studies have to demonstrate.

PMID- 25990686
TI  - Anatomical variants of surgically important landmarks in the sphenoid sinus: a
      radiologic study in Southeast Asian patients.
AB  - PURPOSE: Failure of a surgeon to understand the local variations of the
      anatomical landmarks of the sphenoid sinus is a potential risk factor to cause
      damage to the optic nerve (ON) or internal carotid artery (ICA) that lies on the
      walls of the sphenoid sinus. The aim of this study was to identify the anatomical
      variants of the sphenoid sinus and its related surrounding structures among the
      Southeast Asian (SEA) population, based on computed tomography (CT) scans.
      MATERIALS AND METHODOLOGY: This cross-sectional study analyzed 300 CT scans of
      the brain, paranasal sinuses (PNS), and head and neck (H&N) at a tertiary
      referral centre in Malaysia utilizing the Osirix software. The images were
      reconstructed into 1 mm cuts on bone window. Demographic details and scan
      findings were documented in a standardized data collection sheet. RESULTS: The
      rates of ON dehiscence, ICA dehiscence and ICA protrusion in the SEA population
      were 7.0, 3.0 and 10.0 %, respectively. The rate of ON protrusion was 2.3 %.
      There was no statistically significant relationship (p > 0.05) noted on Chi
      square test, between anterior clinoid process (ACP) pneumatization and ON
      protrusion. The rate of Onodi cells in our population was 14.3 %. The average
      vertical distance of the ostia from the roof of the posterior choanae was 1.42 cm
      (+/-0.32). The horizontal distance of the ostia from the anterior end of the
      superior turbinate was 1.58 cm (+/-0.41) and the oblique distance of the ostia
      from the anterior nasal spine was 5.35 cm (+/-0.48). Independent t tests showed
      that there is a statistically significant difference between the means of each of
      these parameters (p < 0.001) and their international averages. CONCLUSION: The
      rate of ON protrusion is lower in the SEA population, whereas the rates of ON
      dehiscence, ICA dehiscence and ICA protrusion fall within the range of
      international averages. In our population, ACP pneumatization is not related to
      ON protrusion. The distance of the ostia from given landmarks was significantly
      shorter than in other studies.

PMID- 25990687
TI  - The use of PROMIS and the RAND VSQ9 in chiropractic patients receiving care with
      the Webster Technique.
AB  - INTRODUCTION: Our ongoing efforts to demonstrate effectiveness of care examined
      the quality of life (QoL) and patient satisfaction of chiropractic patients
      presenting for care in a PBRN. METHODS: In addition to socio-demographic and
      clinical care information, we examined visit-specific satisfaction and QoL using
      the RAND VSQ and PROMIS-29, respectively. RESULTS: Our study population was
      comprised of 126 subjects (average age = 39.68; 97 females). The majority of
      respondents presented with musculoskeletal complaints with an average mean
      duration of 7.188 years. The mean PROMIS-25 mean T Scores were: depression
      (47.80); pain interference (53.49); fatigue (51.02); physical function (49.02);
      satisfaction with social role (52.10); anxiety (50.14); and sleep disturbance
      (49.88). The VSQ9 mean score was 93.4% indicating high satisfaction. CONCLUSIONS:
      Adults attending care in a chiropractic PBRN were able to successfully complete
      the PROMIS29 and VSQ9 instruments. Future longitudinal studies should quantify
      the minimal clinically important difference in mean T score changes.

PMID- 25990688
TI  - Augmentation with hydroxyapatite graft for treating nasal hypoplasia associated
      with Binderoid complete cleft lip.

PMID- 25990689
TI  - Selenium status and cardiovascular diseases: meta-analysis of prospective
      observational studies and randomized controlled trials.
AB  - BACKGROUND/OBJECTIVES: Selenium was thought to have a role in cardiovascular
      disease (CVD) owing to its antioxidant properties; however, evidence from
      observational studies and randomized controlled trials (RCTs) has been
      inconsistent and controversial. We thus conducted a meta-analysis to assess the
      discrepancies between observational and randomized trial evidence.
      SUBJECTS/METHODS: We searched MEDLINE and EMBASE for eligible prospective studies
      regarding the relationship between selenium and CVD up to 15 December 2013 and
      finally included 16 prospective observational studies and 16 RCTs. Random effects
      model was used to estimate the pooled relative risk (RR). Generalized least
      squares trend test and restricted cubic spline model were performed to assess a
      linear and a nonlinear dose-response relationship. RESULTS: Our meta-analysis of
      prospective studies showed a nonlinear relationship of CVD risk with blood
      selenium concentrations across a range of 30-165 MUg/l and a significant benefit
      of CVD within a narrow selenium range of 55-145 MUg/l. Our meta-analyses of RCTs
      showed that oral selenium supplements (median dose: 200 MUg/day) for 2 weeks to
      144 months significantly raised the blood selenium concentrations by 56.4 MUg/l
      (95% confidence interval (CI): 40.9, 72.0 MUg/l), whereas oral selenium
      supplements (median: 100 MUg/day) for 6 to 114 months caused no effect on CVD
      (RR=0.91; 95% CI: 0.74, 1.10). CONCLUSIONS: Our meta-analysis in prospective
      studies demonstrated a significant inverse association between selenium status
      and CVD risk within a narrow selenium range and a null effect of selenium
      supplementation on CVD was observed in RCTs. These findings indicate the
      importance of considering selenium status, dose and safety in health assessment
      and future study design.

PMID- 25990691
TI  - "Spleen Contraction and Hemoconcentration" Regarding the Review
      "Hemoconcentration and Hemostasis During Acute Stress: Interacting and
      Independent Effects" by Austin et al. 2011.

PMID- 25990690
TI  - Anthropometric reference data for elderly Swedes and its disease-related pattern.
AB  - BACKGROUND/OBJECTIVES: Anthropometric measurement is a noninvasive and cost
      efficient method for nutritional assessment. The study aims to present age- and
      gender-specific anthropometric reference data for Swedish elderly in relation to
      common medical conditions, and also formulate prediction equations for such
      anthropometric measurements. SUBJECTS/METHODS: A cross-sectional study among
      random heterogeneous sample of 3360 subjects, aged 60-99 years, from a population
      study 'Good Aging in Scania. Means (+/-s.d.) and percentiles for height, weight,
      waist-, hip-, arm-, calf circumferences, triceps- (TST) and subscapular skinfold
      thickness (SST), body mass index (BMI), waist-hip ratio (WHR) and arm muscle
      circumference (AMC) were presented. The values were estimated based on the
      prevalence of myocardial infarction (MI), cardiac failure (CHF), stroke,
      cognitive impairment, dementia and dependence in daily living activities (ADL).
      Linear regression analysis was used to formulate the prediction equations.
      RESULTS: Mean BMI was 27.5+/-5.8 kg/m(2) (men) and 27.2+/-8.1 kg/m(2) (women).
      WHR was higher among men (Men: 0.98+/-0.3, women: 0.87+/-0.2), except at age 85+
      (women: 0.91+/-0.6). TST was 6.7+/-0.4 mm higher among women. Men with MI had
      BMI: 28.6+/-4.8 kg/m(2) and SST: 21+/-9.2 mm, whereas subjects with dementia had
      lower weight (by 9.5+/-2.9 kg) compared with the non-demented. ADL-dependent
      women had BMI= 29.0+/-3.9 kg/m(2), TST=19.2+/-1.3 mm. CONCLUSION: New normative
      data on gender- and age-specific anthropometrics on the general elderly
      population are presented. Cardiovascular diseases are associated with
      subcutaneous and central adiposity opposed to fat loss with dementia. ADL
      dependence indicates inadequate physical activity. The prediction models could be
      used as possible indicators monitoring physical activity and adiposity among the
      general elderly population hence potential health indicators in health promotion.

PMID- 25990692
TI  - Comparative histologic and immunologic evaluation of 1,4-butanediol diglycidyl
      ether crosslinked versus noncrosslinked acellular swim bladder matrix for healing
      of full-thickness skin wounds in rabbits.
AB  - BACKGROUND: Collagen-rich extracellular matrix from land-based mammalian tissues
      is increasingly used in regenerative medicine. However, its uses are associated
      with risk of disease transfer and may carry an ethnocultural stigma. In the
      present study, collagen-rich acellular swim bladder matrix (ASBM) from Rohu fish
      was prepared using sodium deoxycholate and crosslinked with 1,4-butanediol
      diglycidyl ether (BDDGE). Wound healing potential of ASBM and ASBM-BDDGE was
      compared in full-thickness skin wounds in rabbits. MATERIALS AND METHODS: Four
      full-thickness skin wounds (20 * 20 mm(2) each) were created on the dorsum of 18
      rabbits and randomly divided into three equal groups. Wounds were left open,
      repaired with ASBM and ASBM-BDDGE in groups sham (I), ASBM (II), and ASBM-BDDGE
      (III), respectively. Planimetry, contracture, immunologic, and histologic
      observations were carried out to evaluate wound healing. RESULTS: Significantly
      (P < 0.05) lesser wound contraction was observed in ASBM (II) and ASBM-BDDGE
      (III) groups compared with sham (I) group. Total immunoglobulin G response in
      rabbit sera was decreased significantly (P < 0.05) in the ASBM-BDDGE (III) group
      compared with ASBM (II) group by enzyme-linked immunosorbent assay. Stimulation
      index of peripheral blood lymphocytes was decreased significantly (P < 0.05) in
      the ASBM-BDDGE (III) group compared with ASBM (II) group by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Histologically,
      improved epithelialization, neovascularization, fibroplasia, and best arranged
      collagen fibers were observed in ASBM (II) and ASBM-BDDGE (III) groups as early
      as on postimplantation day 21. CONCLUSIONS: Findings of this study indicate that
      BDDGE crosslinked ASBM derived from Rohu fish has potential for the clinical
      applications. Furthermore, it is expected that their clinical applications will
      not be limited by ethnocultural stigma.

PMID- 25990693
TI  - Hydrogen sulphide as a novel therapy to ameliorate cyclosporine nephrotoxicity.
AB  - BACKGROUND: Calcineurin inhibitors have significant nephrotoxic side effects,
      which can exacerbate ischemia-reperfusion injury in renal transplantation. Novel
      therapeutic agents such as hydrogen sulphide (H2S) may reduce these harmful
      effects. This study investigated the effects of H2S on cyclosporine (CsA) induced
      nephrotoxicity. MATERIALS AND METHODS: Porcine kidneys were subjected to 15 min
      of warm ischemia and 2 h of static cold storage. They were reperfused for 3 h
      with oxygenated normothermic autologous whole blood on an isolated organ
      reperfusion apparatus. Kidneys were treated with CsA during reperfusion (n = 6)
      or cyclosporine and 0.25 mmol/L of H2S infused 10 min before and 20 min after
      reperfusion (n = 6). These were compared with untreated controls (n = 7).
      RESULTS: CsA caused a significant reduction in renal blood flow during
      reperfusion, which was reversed by H2S (area under the curve renal blood flow CsA
      257 +/- 93 versus control 477 +/- 206 versus CsA + H2S 478 +/- 271 mL/min/100
      g.h; P = 0.024). Urine output was higher after 2 h of reperfusion in the CsA +
      H2S group (CsA + H2S 305 +/- 218 versus CsA 78 +/- 180 versus control 210 +/- 45
      mL; P = 0.034). CsA treatment was associated with an increase in tubular injury,
      which was not reversed by H2S (area under the curve fractional excretion of
      sodium, control 77 +/- 53 versus CsA 100 +/- 61 versus CsA + H2S 111 +/- 57%.h; P
      = 0.003). Histologic evaluation showed significant vacuolation and glomerular
      shrinkage in the CsA group. These were significantly reduced by H2S (P = 0.005,
      0.002). CONCLUSIONS: H2S reversed the vasoconstriction changes associated with
      CsA treatment during reperfusion.

PMID- 25990694
TI  - Simple new risk score model for adult cardiac extracorporeal membrane
      oxygenation: simple cardiac ECMO score.
AB  - BACKGROUND: Although the use of cardiac extracorporeal membrane oxygenation
      (ECMO) is increasing in adult patients, the field lacks understanding of
      associated risk factors. While standard intensive care unit risk scores such as
      SAPS II (simplified acute physiology score II), SOFA (sequential organ failure
      assessment), and APACHE II (acute physiology and chronic health evaluation II),
      or disease-specific scores such as MELD (model for end-stage liver disease) and
      RIFLE (kidney risk, injury, failure, loss of function, ESRD) exist, they may not
      apply to adult cardiac ECMO patients as their risk factors differ from variables
      used in these scores. METHODS: Between 2010 and 2014, 73 ECMOs were performed for
      cardiac support at our institution. Patient demographics and survival were
      retrospectively analyzed. A new easily calculated score for predicting ECMO
      mortality was created using identified risk factors from univariate and
      multivariate analyses, and model discrimination was compared with other scoring
      systems. RESULTS: Cardiac ECMO was performed on 73 patients (47 males and 26
      females) with a mean age of 48 +/- 14 y. Sixty-four percent of patients (47/73)
      survived ECMO support. Pre-ECMO SAPS II, SOFA, APACHE II, MELD, RIFLE, PRESERVE,
      and ECMOnet scores, were not correlated with survival. Univariate analysis of pre
      ECMO risk factors demonstrated that increased lactate, renal dysfunction, and
      postcardiotomy cardiogenic shock were risk factors for death. Applying these data
      into a new simplified cardiac ECMO score (minimal risk = 0, maximal = 5)
      predicted patient survival. Survivors had a lower risk score (1.8 +/- 1.2) versus
      the nonsurvivors (3.0 +/- 0.99), P < 0.0001. CONCLUSIONS: Common intensive care
      unit or disease-specific risk scores calculated for cardiac ECMO patients did not
      correlate with ECMO survival, whereas a new simplified cardiac ECMO score
      provides survival predictability.

PMID- 25990695
TI  - One-year postoperative resource utilization in sarcopenic patients.
AB  - BACKGROUND: It is well established that sarcopenic patients are at higher risk of
      postoperative complications and short-term health care utilization. Less well
      understood is how these patients fare over the long term after surviving the
      immediate postoperative period. We explored costs over the first postoperative
      year among sarcopenic patients. METHODS: We identified 1279 patients in the
      Michigan Surgical Quality Collaborative database who underwent inpatient elective
      surgery at a single institution from 2006-2011. Sarcopenia, defined by gender
      stratified tertiles of lean psoas area, was determined from preoperative computed
      tomography scans using validated analytic morphomics. Data were analyzed to
      assess sarcopenia's relationship to costs, readmissions, discharge location,
      intensive care unit admissions, hospital length of stay, and mortality.
      Multivariate models were adjusted for patient demographics and surgical risk
      factors. RESULTS: Sarcopenia was independently associated with increased adjusted
      costs at 30, 90, and 180 but not 365 d. The difference in adjusted postsurgical
      costs between sarcopenic and nonsarcopenic patients was $16,455 at 30 d and
      $14,093 at 1 y. Sarcopenic patients were more likely to be discharged somewhere
      other than home (P < 0.001). Sarcopenia was not an independent predictor of
      increased readmission rates in the postsurgical year. CONCLUSIONS: The effects of
      sarcopenia on health care costs are concentrated in the immediate postoperative
      period. It may be appropriate to allocate additional resources to sarcopenic
      patients in the perioperative setting to reduce the incidence of negative
      postoperative outcomes.

PMID- 25990696
TI  - Matrix Gla protein regulates calcification of the aortic valve.
AB  - BACKGROUND: The aortic valve interstitial cell (AVIC) has been implicated in the
      pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the
      AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that
      of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an
      important inhibitor of vascular calcification. We therefore hypothesized that MGP
      expression is reduced in diseased AVICs, and loss of this protective protein
      contributes to calcification of the aortic valve. Our purpose was to compare MGP
      expression in normal versus diseased AVICs. MATERIALS AND METHODS: Human AVICs
      were isolated from normal aortic valves from explanted hearts (n = 6) at the time
      of heart transplantation. AVICs were also isolated from calcified, diseased
      valves of patients (n = 6) undergoing aortic valve replacement. AVICs were grown
      in culture until they reached passages 2-6 before experimentation.
      Immunofluorescent staining, reverse transcriptase-polymerase chain reaction,
      immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels
      of MGP in normal and diseased AVICs. Statistics were performed using the Mann
      Whitney U test (P < 0.05). RESULTS: MGP expression was significantly decreased in
      diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse
      transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked
      immunosorbent assay. CONCLUSIONS: An important anti-calcification defense
      mechanism is deficient in calcified aortic valves. MGP expression is
      significantly lower in diseased relative to normal AVICs. Lack of this important
      "anti-calcification" protein may contribute to calcification of the aortic valve.

PMID- 25990697
TI  - Identifying neuroanatomical signatures of anorexia nervosa: a multivariate
      machine learning approach.
AB  - BACKGROUND: There are currently no neuroanatomical biomarkers of anorexia nervosa
      (AN) available to make clinical inferences at an individual subject level. We
      present results of a multivariate machine learning (ML) approach utilizing
      structural neuroanatomical scan data to differentiate AN patients from matched
      healthy controls at an individual subject level. METHOD: Structural neuroimaging
      scans were acquired from 15 female patients with AN (age = 20, s.d. = 4 years)
      and 15 demographically matched female controls (age = 22, s.d. = 3 years).
      Neuroanatomical volumes were extracted using the FreeSurfer software and input
      into the Least Absolute Shrinkage and Selection Operator (LASSO) multivariate ML
      algorithm. LASSO was 'trained' to identify 'novel' individual subjects as either
      AN patients or healthy controls. Furthermore, the model estimated the probability
      that an individual subject belonged to the AN group based on an individual scan.
      RESULTS: The model correctly predicted 25 out of 30 subjects, translating into
      83.3% accuracy (sensitivity 86.7%, specificity 80.0%) (p < 0.001; chi 2 test).
      Six neuroanatomical regions (cerebellum white matter, choroid plexus, putamen,
      accumbens, the diencephalon and the third ventricle) were found to be relevant in
      distinguishing individual AN patients from healthy controls. The predicted
      probabilities showed a linear relationship with drive for thinness clinical
      scores (r = 0.52, p < 0.005) and with body mass index (BMI) (r = -0.45, p =
      0.01). CONCLUSIONS: The model achieved a good predictive accuracy and drive for
      thinness showed a strong neuroanatomical signature. These results indicate that
      neuroimaging scans coupled with ML techniques have the potential to provide
      information at an individual subject level that might be relevant to clinical
      outcomes.

PMID- 25990699
TI  - Prevalence, management and burden of episodic and chronic headaches--a cross
      sectional multicentre study in eight Austrian headache centres.
AB  - BACKGROUND: Episodic and chronic headaches (EH, CH) are highly prevalent
      disorders. Severely affected patients are usually referred to headache centres.
      In Austria, at least one headache centre is available in seven of nine states,
      but detailed multicentre data are missing. Therefore we studied prevalence rates,
      use of medication and health care services, impact of headaches, and comorbid
      depression and anxiety. METHODS: We included consecutive patients from eight
      Austrian outpatient headache centres. The patients filled-in the Eurolight
      questionnaire. In addition, the treating neurologist completed a questionnaire on
      clinical diagnoses and ever-before prophylactic medications. RESULTS: Of 598
      patients screened, 441 questionnaires were analysed (79 % female, mean age 41.1
      years). According to the Eurolight algorithm, 56.4 % of the patients had EH, 38.3
      % had CH and 5.2 % did not give their headache frequency. The prevalence rates of
      migraine, tension-type headache, and probable medication overuse headache (pMOH)
      were 48.5 %, 6.3 % and 15.9 %, respectively. The concordance between clinical and
      Eurolight diagnoses was good for EH and moderate for CH. During the preceding
      month, acute medication was used by 90.9 % of the patients and prophylactic
      medication by 34 %. Ever-before use of five standard prophylactic drugs was
      recorded in 52.3 %. The proportion of patients with current pharmacoprophylaxis
      did not differ in EH and CH, whereas ever-before use was more common in CH (62.5
      % was 45,3 %, p = 0.02). Patients with CH significantly more often consulted
      general practitioners and emergency departments, had a lower quality of life and
      more often signs of depression and anxiety. CONCLUSION: This study provides
      comprehensive data from eight Austrian headache centres for the first time. We
      found a substantial number of patients with CH including pMOH and its association
      with more common utilization of health care facilities and greater burden. The
      low use of prophylactic medication requires further examination.

PMID- 25990701
TI  - Practices to Reduce Surgical Site Infections Among Women Undergoing Cesarean
      Section: A Review.
AB  - OBJECTIVE: Surgical site infections (SSIs) are a leading cause of morbidity and
      mortality among women undergoing cesarean section (C-section), a common procedure
      in North America. While risk factors for SSI are often modifiable, wide variation
      in clinical practice exists. With this review, we provide a comprehensive
      overview of the results and quality of systematic reviews and meta-analyses on
      interventions to reduce surgical site infections among women undergoing C
      section. METHODS: We searched PubMed and the Cochrane Database of Systematic
      Reviews for systematic reviews and meta-analyses published between January 2000
      and May 2014 on interventions to reduce the occurrence of SSIs (incisional
      infections and endometritis), among women undergoing C-section. We extracted data
      on the interventions, outcomes, and strength of evidence as determined by the
      original article authors, and assessed the quality of each article based on a
      modified Assessment of Multiple Systematic Reviews tool. RESULTS: A total of 30
      review articles met inclusion criteria and were reviewed. Among these articles,
      77 distinct interventions were evaluated: 29% were supported with strong evidence
      as assessed by the original article authors, and 83% of the reviews articles were
      classified as good quality based on our assessment. Ten interventions were
      classified as being effective in reducing SSI with strong evidence in a good
      quality article, including preoperative vaginal cleansing, the use of
      perioperative antibiotic prophylaxis, and several surgical techniques.
      CONCLUSION: Efforts to reduce SSI rates among women undergoing C-section should
      include interventions such as preoperative vaginal cleansing and the use of
      perioperative antibiotics because compelling evidence exists to support their
      effectiveness.

PMID- 25990700
TI  - Expression of cell cycle-regulated genes and prostate cancer prognosis in a
      population-based cohort.
AB  - BACKGROUND: Prostate cancer (PCa) is clinically and biologically heterogeneous,
      making it difficult to predict at detection whether it will take an indolent or
      aggressive disease course. Cell cycle-regulated genes may be more highly
      expressed in actively dividing cells, with transcript levels reflecting tumor
      growth rate. Here, we evaluated expression of cell cycle genes in relation to PCa
      outcomes in a population-based cohort. METHODS: Gene expression data were
      generated from tumor tissues obtained at radical prostatectomy for 383 population
      based patients (12.3-years average follow-up). The overall mean and individual
      transcript levels of 30 selected cell cycle genes was compared between patients
      with no evidence of recurrence (73%) and those who recurred (27%) or died (7%)
      from PCa. RESULTS: The multivariate adjusted hazard ratio (HR) for a change from
      the 25th to 75th percentile of mean gene expression level (range 8.02-10.05) was
      1.25 (95%CI 0.96-1.63; P = 0.10) for PCa recurrence risk, and did not vary
      substantially by Gleason score, TMPRSS2-ERG fusion status, or family history of
      PCa. For lethal PCa, the HR for a change (25th to 75th percentile) in mean gene
      expression level was 2.04 (95%CI 1.26-3.31; P = 0.004), adjusted for
      clinicopathological variables. The ROC curve for mean gene expression level alone
      (AUC = 0.740) did not perform as well as clinicopathological variables alone (AUC
      = 0.803) for predicting lethal PCa, and the addition of mean gene expression to
      clinicopathological variables did not substantially improve prediction (AUC =
      0.827; P = 0.18). Higher TK1 expression was strongly associated with both
      recurrent (P = 6.7 * 10(-5)) and lethal (P = 6.4 * 10(-6)) PCa. CONCLUSIONS: Mean
      expression level for 30 selected cell cycle-regulated genes was unrelated to
      recurrence risk, but was associated with a twofold increase in risk of lethal
      PCa. However, gene expression had less discriminatory accuracy than clinical
      variables alone for predicting lethal events. Transcript levels for several genes
      in the panel were significantly overexpressed in lethal versus non-recurrent PCa.

PMID- 25990702
TI  - Welfare effects of a disease eradication programme for dairy goats.
AB  - The Norwegian dairy goat industry has largely succeeded in controlling caprine
      arthritis encephalitis (CAE), caseous lymphadenitis (CLA) and paratuberculosis
      through a voluntary disease eradication programme called Healthier Goats (HG).
      The aim of this study was to apply an on-farm welfare assessment protocol to
      assess the effects of HG on goat welfare. A total of 30 dairy goat farms were
      visited, of which 15 had completed disease eradication and 15 had not yet
      started. Three trained observers assessed the welfare on 10 farms each. The
      welfare assessment protocol comprised both resource-based and animal-based
      welfare measures, including a preliminary version of qualitative behavioural
      assessments with five prefixed terms. A total of 20 goats in each herd were
      randomly selected for observations of human-animal interactions and physical
      health. The latter included registering abnormalities of eyes, nostrils, ears,
      skin, lymph nodes, joints, udder, claws and body condition score. For individual
      level data, robust clustered logistic regression analyses with farm as cluster
      variable were conducted to assess the association with disease eradication.
      Wilcoxon rank-sum tests were used for comparisons of herd-level data between the
      two groups. Goats with swollen joints (indicative of CAE) and enlarged lymph
      nodes (indicative of CLA) were registered on 53% and 93% of the non-HG farms,
      respectively, but on none of the HG farms. The only other health variables with
      significantly lower levels in HG herds were skin lesions (P=0.008) and damaged
      ears due to torn out ear tags (P<0.001). Goats on HG farms showed less fear of
      unknown humans (P=0.013), and the qualitative behavioural assessments indicated
      that the animals in these herds were calmer than in non-HG herds. Significantly
      more space and lower gas concentrations reflected the upgrading of buildings
      usually done on HG farms. In conclusion, HG has resulted in some welfare
      improvements beyond the elimination of infectious diseases. The protocol was
      considered a useful tool to evaluate the welfare consequences of a disease
      eradication programme. However, larger sample sizes would increase the
      reliability of prevalence estimates for less common conditions and increase the
      power to detect differences between the groups. Despite the obvious link between
      disease and suffering, this aspect is rarely taken into account in the evaluation
      of disease control programmes. We therefore propose that welfare assessment
      protocols should be applied to evaluate the merits of disease control or
      eradication programmes in terms of animal welfare. 

PMID- 25990705
TI  - Reducing salt in bread: a quasi-experimental feasibility study in a bakery in
      Lima, Peru.
AB  - OBJECTIVES: To explore salt content in bread and to evaluate the feasibility of
      reducing salt contained in 'pan frances' bread. DESIGN: The study had two phases.
      Phase 1, an exploratory phase, involved the estimation of salt contained in bread
      as well as a triangle taste test to establish the amount of salt to be reduced in
      'pan frances' bread without detection by consumers. In Phase 2, a quasi
      experimental, pre-post intervention study assessed the effects of the
      introduction of low-salt bread on bakery sales. SETTING: A municipal bakery in
      Miraflores, Lima, Peru. SUBJECTS: Sixty-five clients of the bakery in Phase 1 of
      the study; sales to usual costumers in Phase 2. RESULTS: On average, there was
      1.25 g of salt per 100 g of bread. Sixty-five consumers were enrolled in the
      triangle taste test: fifty-four (83.1 %) females, mean age 58.9 (sd 13.7) years.
      Based on taste, bread samples prepared with salt reductions of 10 % (P=0.82) and
      20 % (P=0.37) were not discernible from regular bread. The introduction of bread
      with 20 % of salt reduction, which contained 1 g of salt per 100 g of bread, did
      not change sales of 'pan frances' (P=0.70) or other types of bread (P=0.36).
      Results were consistent when using different statistical techniques. CONCLUSIONS:
      The introduction of bread with a 20 % reduction in salt is feasible without
      affecting taste or bakery sales. Results suggest that these interventions are
      easily implementable, with the potential to contribute to larger sodium reduction
      strategies impacting the population's cardiovascular health.

PMID- 25990704
TI  - Effects of sex, menstrual cycle phase, and endogenous hormones on cognition in
      schizophrenia.
AB  - BACKGROUND: In women with schizophrenia, cognition has been shown to be enhanced
      following administration of hormone therapy or oxytocin. We examined how natural
      hormonal changes across the menstrual cycle influence cognition in women with
      schizophrenia. We hypothesized that female patients would perform worse on
      "female-dominant" tasks (verbal memory/fluency) and better on "male-dominant"
      tasks (visuospatial) during the early follicular phase (low estradiol and
      progesterone) compared to midluteal phase (high estradiol and progesterone) in
      relation to estradiol but not progesterone. METHODS: Fifty-four women (23 with
      schizophrenia) completed cognitive assessments and provided blood for sex steroid
      assays and oxytocin at early follicular (days 2-4) and midluteal (days 20-22)
      phases. Men were included to verify the expected pattern of sex differences on
      cognitive tests. RESULTS: Expected sex differences were observed on "female
      dominant" and "male-dominant" tasks (p<0.001), but the magnitude of those
      differences did not differ between patients and controls (p=0.44). Cognitive
      performance did not change across the menstrual cycle on "female-dominant" or
      "male-dominant" tasks in either group. Estradiol and progesterone levels were
      unrelated to cognitive performance. Oxytocin levels did not change across the
      menstrual cycle but were positively related to performance on "female-dominant"
      tasks in female patients only (p<0.05). CONCLUSIONS: Sex differences in cognitive
      function are preserved in schizophrenia. Oxytocin levels do not change across the
      cycle, but relate to enhanced performance on female dominant tests in women.
      Physiological levels of oxytocin may thus have a more powerful benefit in some
      cognitive domains than estrogens in schizophrenia.

PMID- 25990706
TI  - Low postoperative dietary intake is associated with worse functional course in
      geriatric patients up to 6 months after hip fracture.
AB  - We examined the relationship between postoperative dietary intake (DI) of
      geriatric hip fracture (HF) patients and their functional and clinical course
      until 6 months after hospital discharge. In eighty-eight HF patients >= 75 years,
      postoperative DI was estimated with plate diagrams of main meals over four
      postoperative days. DI was stratified as >50, >25-50, <= 25 % of meals served.
      Functional status according to Barthel index (activities of daily living) and
      patients' mobility level before fracture, postoperatively, at discharge and 6
      months later were assessed and related to DI levels. In-hospital complications
      were recorded according to clinical diagnosis. Associations were evaluated using
      chi2 and Kruskal-Wallis tests, and repeated-measures ANOVA and ANCOVA.
      Postoperatively, 28 % of participants ate >50 %, 43 % ate >25-50 % and 28 % <= 25
      % of meals served. Irrespective of pre-fracture functional status, patients with
      DI <= 25 % had significantly lower Barthel index scores at all times after
      surgery (all P50 % more often had regained their pre-fracture mobility level than
      those with DI <= 25 % at discharge (>50 %: 36 %; >25-50 %: 10 %; <= 25 %: 0 %; P=
      0.001) and 6 months after discharge (88; 87; 68 %; P= 0.087) and had
      significantly less complications (median 2 (25th-75th percentile 1-3); 3 (25th
      75th percentile 2-4); 3 (25th-75th percentile 3-4); P= 0.012). To conclude,
      geriatric HF patients had very low postoperative voluntary DI and thus need
      specific nutritional interventions to achieve adequate DI to support functional
      and clinical recovery. 

PMID- 25990707
TI  - Constructing minimal models for complex system dynamics.
AB  - One of the strengths of statistical physics is the ability to reduce macroscopic
      observations into microscopic models, offering a mechanistic description of a
      system's dynamics. This paradigm, rooted in Boltzmann's gas theory, has found
      applications from magnetic phenomena to subcellular processes and epidemic
      spreading. Yet, each of these advances were the result of decades of meticulous
      model building and validation, which are impossible to replicate in most complex
      biological, social or technological systems that lack accurate microscopic
      models. Here we develop a method to infer the microscopic dynamics of a complex
      system from observations of its response to external perturbations, allowing us
      to construct the most general class of nonlinear pairwise dynamics that are
      guaranteed to recover the observed behaviour. The result, which we test against
      both numerical and empirical data, is an effective dynamic model that can predict
      the system's behaviour and provide crucial insights into its inner workings. 

PMID- 25990708
TI  - SERS substrates fabricated with star-like gold nanoparticles for zeptomole
      detection of analytes.
AB  - This work presents the design of substrates for Surface Enhanced Raman Scattering
      (SERS) using star-like gold nanoparticles which were synthesized using a wet
      chemical method and functionalized with 1-dodecanethiol. This molecule allowed us
      to obtain a spacing of ~2.6 nm among gold stars, which promoted the generation of
      SERS hotspots for single molecule detection. The gold nanoparticles were
      deposited on silicon substrates or on gold coated silicon substrates by using the
      Langmuir-Blodgett method which permitted the zeptomole detection of Rhodamine B
      (total moles per laser spot area). The Raman enhancement factor (EF) achieved for
      this level of detection was 10(12), and was obtained on the SERS substrate
      fabricated with the configuration: Si/Au film/Au nanoparticles. Raman spectra of
      the molecules TWEEN 20 and p-terphenyl were also measured in order to elucidate
      the effect of the molecule's length on the enhancement factor. According to these
      results, our SERS substrates without the gold film are useful for a minimum
      detection level of ~10(-14) moles of analytes with sizes equal to or less than
      1.3 nm and ~10(-18) moles of analytes with the gold film (total moles per
      sample). 

PMID- 25990709
TI  - The mystery of post-axial polydactyly in Renaissance paintings.

PMID- 25990711
TI  - Hierarchical Molybdenum Nitride Nanochexes by a Textured Self-Assembly in Gas
      Solid Phase for the Enhanced Application in Lithium Ion Batteries.
AB  - Self-assembly, as one kind of general phenomenon, has often been reported in
      solution chemistry. However, in gas-solid phase, it seldom has been disclosed.
      The MoN nanochex exhibits unique geometrical shape. Its body segment is composed
      of textured single crystal MoN nanowires, while its edges parallel to [122]
      direction are attached by nanowires whose crystal orientation is different from
      that of the body segment. In this paper, the structure of the MoN nanochex is
      studied, and accordingly, a possible growth mechanism is proposed. We expect to
      extend this method to designed synthesis of many other functional materials, such
      as nitrides, carbides, and borides, and thereby to significantly tailor their
      resulting properties. Meanwhile, as one promising electrode material for Li-ion
      batteries (LIBs), MoN nanochex on Ti foil has been applied in the electrochemical
      energy storage, and stably delivered a specific capacity of 720 mAh/g with a
      remarkable Coulombic efficiency up to 98.5%, implying an achieved synergic effect
      derived from both mesoporous structure and the direct contact with the conducting
      substrate. 

PMID- 25990710
TI  - Reversed electrogenic sodium bicarbonate cotransporter 1 is the major acid loader
      during recovery from cytosolic alkalosis in mouse cortical astrocytes.
AB  - KEY POINTS: The regulation of H(+) i from cytosolic alkalosis has generally been
      attributed to the activity of Cl(-) -coupled acid loaders/base extruders in most
      cell types, including brain cells. The present study demonstrates that outwardly
      directed sodium bicarbonate cotransport via electrogenic sodium bicarbonate
      cotransporter 1 (NBCe1) mediates the major fraction of H(+) i regulation from
      cytosolic alkalosis in mouse cortical astrocytes. Cl(-) -coupled acid-loading
      transporters play only a minor role in the regulation of H(+) i from alkalosis in
      mouse cortical astrocytes. NBCe1-mediated H(+) i regulation from alkalosis was
      dominant, with the support of intracellular carbonic anhydrase II, even when the
      intra- and extracellular [HCO3 (-) ] was very low (<1mM), as in nominally CO2
      /HCO3 (-) free condition. A reversed NBCe1 in astrocytes may also be significant
      for stabilizing extracellular pH in brain tissue. ABSTRACT: Recovery of
      intracellular pH from cytosolic alkalosis has been attributed primarily to Cl(-)
      coupled acid loaders/base extruders such as Cl(-) /HCO3 (-) or Cl(-) /OH(-)
      exchangers. We have studied this process in cortical astrocytes from wild-type
      and transgenic mouse models with gene deletion for the electrogenic sodium
      bicarbonate cotransporter 1 (NBCe1) and for carbonic anhydrase (CA) isoform II.
      An acute cytosolic alkalosis was induced by the removal of either CO2 /HCO3 (-)
      or butyric acid, and the subsequent acid loading was analysed by monitoring
      changes in cytosolic H(+) or Na(+) using ion-sensitive fluorescent dyes. We have
      identified that NBCe1 reverses during alkalosis and contributes more than 70% to
      the rate of recovery from alkalosis by extruding Na(+) and HCO3 (-) . After CA
      inhibition or in CAII-knockout (KO) cells, the rate of recovery was reduced by
      40%, and even by 70% in the nominal absence of CO2 /HCO3 (-) . Increasing the
      extracellular K(+) concentration modulated the rate of acid loading in wild-type
      cells, but not in NBCe1-KO cells. Removing chloride had only a minor effect on
      the recovery from alkalosis. Reversal of NBCe1 by reducing pH/[HCO3 (-) ] was
      demonstrated in astrocytes and in Xenopus oocytes, in which human NBCe1 was
      heterologously expressed. The results obtained suggest that reversed NBCe1,
      supported by CAII activity, plays a major role in acid-loading cortical
      astrocytes to support recovery from cytosolic alkalosis.

PMID- 25990712
TI  - Acute ischaemic stroke patients - direct admission to a specialist centre or
      initial treatment in a local hospital? A systematic review.
AB  - OBJECTIVES: To assess the clinical effectiveness, in acute ischaemic stroke
      patients, of bypassing non-specialist centres in preference for a specialist
      stroke centre to receive the time-critical intervention of thrombolysis. METHODS:
      Systematic review and meta-analysis using: MEDLINE; MEDLINE In-Process; EMBASE;
      CINAHL; Cochrane Library including Cochrane Database of Systematic Reviews,
      Cochrane CENTRAL Controlled Trials Register, DARE, NHS EED and HTA databases.
      Studies were included if they compared acute ischaemic stroke patients directly
      triaged to a specialist centre versus those initially triaged to a non-specialist
      centre with some or all later transferred to a specialist centre. Studies were
      excluded if they compared patients ever treated in a specialist centre versus
      those never treated in such a centre, since the aim was to assess the optimum
      initial triage route rather than the optimum location for overall management. The
      assumption being, based on previous research, that management in a specialist
      centre leads to better patient outcomes. RESULTS: Fourteen studies investigating
      2790 patients were identified. Studies comparing commencement of thrombolysis in
      non-specialist centres versus the specialist centres (n=1394) showed no
      significant difference in unadjusted mortality (OR = 0.89; 95% CI = 0.61-1.30) or
      morbidity (favourable modified Rankin Score, n = 899) (OR = 1.16; 95% CI = 0.85
      1.59) among thrombolysed patients. In studies where thrombolysis could only be
      administered in a specialist centre, data for patients arriving within the
      therapeutic window (n = 140) revealed significantly higher mortality for those
      initially admitted to a non-specialist centre compared to directly admitted to a
      specialist centre (OR = 6.62; 95% CI = 2.60-16.82); morbidity data also favoured
      direct admission to a specialist centre, although not consistently. CONCLUSIONS:
      For ischaemic stroke patients, the location of initial thrombolysis treatment
      does not affect outcomes. However, if thrombolysis is only available at a
      specialist centre, outcomes are considerably better for those patients admitted
      directly. However, these conclusions are based on poor quality data with small
      sample populations, significant heterogeneity and subject to confounding.

PMID- 25990713
TI  - Molecular dynamics simulation of amplitude modulation atomic force microscopy.
AB  - Molecular dynamics (MD) simulations were used to model amplitude modulation
      atomic force microscopy (AM-AFM). In this novel simulation, the model AFM tip
      responds to both tip-substrate interactions and to a sinusoidal excitation
      signal. The amplitude and phase shift of the tip oscillation observed in the
      simulation and their variation with tip-sample distance were found to be
      consistent with previously reported trends from experiments and theory. These
      simulation results were also fit to an expression enabling estimation of the
      energy dissipation, which was found to be smaller than that in a corresponding
      experiment. The difference was analyzed in terms of the effects of tip size and
      substrate thickness. Development of this model is the first step toward using MD
      to gain insight into the atomic-scale phenomena that occur during an AM-AFM
      measurement. 

PMID- 25990714
TI  - A simple decision rule including D-dimer to reduce the need for computed
      tomography scanning in patients with suspected pulmonary embolism.
AB  - BACKGROUND: An 'unlikely' clinical decision rule with a negative D-dimer result
      safely excludes pulmonary embolism (PE) in 30% of presenting patients. We aimed
      to simplify this diagnostic approach and to increase its efficiency. METHODS:
      Data for 723 consecutive patients with suspected PE were analyzed (prevalence of
      PE, 22%). After constructing a logistic regression model with the D-dimer test
      result and items from the Wells' score, we identified the most prevalent
      combinations of influential items and selected new D-dimer positivity thresholds.
      The performance was separately validated with data from 2785 consecutive patients
      with suspected PE. RESULTS: Three Wells items significantly added incremental
      value to the D-dimer test: hemoptysis, signs of deep vein thrombosis and 'PE most
      likely'. Based on the most frequent combinations of these three items, we
      identified two groups: (i) none of these three items positive (41%); (ii) one or
      more of these items positive (59%). When applying a 1000 MUg/L D-dimer threshold
      in group 1 and 500 MUg/L in group 2, PE could be excluded without CT scanning in
      36%, at a false-negative rate of 1.2% (95%, 0.04-3.3%). In the validation set,
      these proportions were 46% and 1.9% (95% CI, 1.2-2.7%), respectively. Using the
      conventional Wells score with a normal D-dimer result, these rates were,
      respectively, 22% and 0.6% (95% CI, 0.10-2.4%). CONCLUSION: Combining Wells items
      with the D-dimer test resulted in a simplified decision rule, which reduces the
      need for CT scanning in patients with suspected PE. A prospective validation is
      required before it can be implemented in clinical practice.

PMID- 25990715
TI  - Coverage, use and maintenance of bed nets and related influence factors in Kachin
      Special Region II, northeastern Myanmar.
AB  - BACKGROUND: Myanmar is one of the 31 highest burden malaria countries worldwide.
      Scaling up the appropriate use of insecticide-treated nets (ITNs) is a national
      policy for malaria prevention and control. However, the data on use, influencing
      factors and maintenance of bed nets is still lack among the population in Kachin
      Special Region II (KR2), Northeastern Myanmar. METHODS: The study combined a
      quantitative household questionnaire survey and qualitative direct observation of
      households. A Chi-squared test was used to compare the percentages of ownership,
      coverage, and rates of use of bed nets. Additionally, multivariate logistic
      regression analysis (MVLRA) was used to analyse factors that influence the use of
      bed nets. Finally, covariance compared the mean calibrated hole indexes (MCHI)
      across potential influence variables. RESULTS: The bed net to person ratio was
      1:1.96 (i.e., more than one net for every two people). The long-lasting
      insecticidal net (LLIN) to person ratio was 1: 2.52. Also, the percentage of
      households that owned at least one bed net was 99.7% (666/688). Some 3262 (97.3%)
      residents slept under bed nets the prior night, 2551 (76.1%) of which slept under
      ITNs/LLINs the prior night (SUITNPN). The poorest families, those with thatched
      roofing, those who use agriculture as their main source of family income,
      household heads who knew that mosquitoes transmit malaria and those who used bed
      nets to prevent malaria, were significantly more likely to be in the SUITNPN
      group. However, residents in lowlands, and foothills were significantly less
      likely to be SUITNPNs. Finally, head of household attitude towards fixing bed
      nets influenced MCHI (F=8.09, P=0.0046). CONCLUSIONS: The coverage and usage
      rates of bed nets were high, especially among children, and pregnant women.
      Family wealth index, geographical zones, household roofing, source of family
      income, household head's knowledge of malaria transmission and of using bed nets
      as tools for malaria prevention are all independent factors which influence use
      of ITNs/LLINs in KR2. Maintaining high coverage, and use rate of bed nets should
      be a priority for the war-torn population of KR2 to ensure equity and human
      rights.

PMID- 25990716
TI  - Presidential address: Will victims see justice at last?

PMID- 25990718
TI  - Lung Cancer Diagnosis and Treatment as a Traumatic Stressor in DSM-IV and DSM-5:
      Prevalence and Relationship to Mental Health Outcomes.
AB  - Little research has examined how lung cancer survivors whose cancer experience
      met the Diagnostic and Statistical Manual of Mental Disorders (DSM) traumatic
      stressor criterion differ with regard to posttreatment mental health status from
      survivors whose cancer experience did not. No research of which we are aware has
      examined the impact of the revised DSM-5 traumatic stressor criterion on this
      question. Non-small-cell (NSC) lung cancer survivors (N = 189) completed a
      telephone interview and questionnaire assessing distress and growth/benefit
      finding. Survivors were categorized into Trauma and No Trauma groups using both
      the DSM-IV and DSM-5 stressor criterion. Using the DSM-IV criterion, the Trauma
      group (n = 70) reported poorer status than the No Trauma group (n = 119) on 10 of
      10 distress indices (mean ES = 0.57 SD) and better status on all 7 growth/benefit
      finding indices (mean ES = 0.30 SD). Using the DSM-5 stressor criterion,
      differences between the Trauma (n = 108) and No Trauma (n = 81) groups for
      indices of distress (mean ES = 0.26 SD) and growth/benefit-finding (mean ES =
      0.17 SD) were less pronounced. Those who experience cancer as a traumatic
      stressor show greater distress and growth/benefit-finding, particularly when the
      more restrictive DSM-IV stressor criterion defines trauma exposure. 

PMID- 25990717
TI  - Protective natural autoantibodies to apoptotic cells: evidence of convergent
      selection of recurrent innate-like clones.
AB  - During murine immune development, recurrent B cell clones arise in a predictable
      fashion. Among these B cells, an archetypical clonotypic set that recognizes
      phosphorylcholine (PC) antigens and produces anti-PC IgM, first implicated for
      roles in microbial protection, was later found to become expanded in
      hyperlipidemic mice and in response to an increased in vivo burden of apoptotic
      cells. These IgM natural antibodies can enhance clearance of damaged cells and
      induce intracellular blockade of inflammatory signaling cascades. In clinical
      populations, raised levels of anti-PC IgM correlate with protection from
      atherosclerosis and may also downmodulate the severity of autoimmune disease.
      Human anti-PC-producing clones without hypermutation have been isolated that can
      similarly discriminate apoptotic from healthy cells. An independent report on
      unrelated adults has described anti-PC-producing B cells with IgM genes that have
      conserved CDR3 motifs, similar to stereotypic clonal sets of B cell chronic
      lymphocytic leukemia. Taken together, emerging evidence suggests that, despite
      the capacity to form an effectively limitless range of Ig receptors, the human
      immune system may often recurrently generate lymphocytes expressing structurally
      convergent B cell receptors with protective and homeostatic roles. 

PMID- 25990719
TI  - Occurrence and hydrogeochemical characteristics of high-fluoride groundwater in
      Xiji County, southern part of Ningxia Province, China.
AB  - High-F(-) groundwater is widely distributed in Xiji County, which endangers the
      safety of drinking water. In order to evaluate the key factors controlling the
      origin and geochemical mechanisms of F(-) enrichment in groundwater at Xiji
      County, one hundred and five groundwater samples and sixty-two sediment samples
      were collected. Fluoride concentration in the groundwater samples ranged from 0.2
      to 3.01 mg/L (mean 1.13 mg/L), with 17 % exceeding the WHO drinking water
      guideline value of 1.5 mg/L and 48 % exceeding the Chinese drinking water
      guideline value of 1.0 mg/L. High-F(-) groundwaters were characterized by
      hydrochemical types of Na-HCO3 and Na-SO4.Cl, which were found in Quaternary
      sediment aquifer and in Tertiary clastic aquifer, respectively. Conditions
      favorable for F(-) enrichment in groundwater included weakly alkaline pH (7.2
      8.9), low concentration of Ca(2+), and high concentrations of HCO3 (-) and Na(+).
      Calcite and fluorite were the main minerals controlling F(-) concentration in
      groundwaters. The hydrolysis of F-bearing minerals in aquifer sediments was the
      more important process for F(-) release in Tertiary clastic aquifer, which was
      facilitated by long residence time of groundwater, in comparison with Quaternary
      sediment aquifer. Cation exchange would also play important roles, which removed
      Ca(2+) and Mg(2+) and led to more free mobility of F(-) in groundwater and
      permitted dissolution of fluorite, especially in Tertiary clastic aquifer.
      However, evapotranspiration and competing adsorption of B and HCO3 (-) were the
      more important processes for F(-) enrichment in Quaternary groundwater.
      Groundwater in Lower Cretaceous aquifer had relatively low F(-) concentration,
      which was considered to be the potential drinking water resource. 

PMID- 25990720
TI  - Significant expansion of the REST/NRSF cistrome in human versus mouse embryonic
      stem cells: potential implications for neural development.
AB  - Recent studies have employed cross-species comparisons of transcription factor
      binding, reporting significant regulatory network 'rewiring' between species.
      Here, we address how a transcriptional repressor targets and regulates neural
      genes differentially between human and mouse embryonic stem cells (ESCs). We find
      that the transcription factor, Repressor Element 1 Silencing Transcription factor
      (REST; also called neuron restrictive silencer factor) binds to a core group of
      ~1200 syntenic genomic regions in both species, with these conserved sites highly
      enriched with co-factors, selective histone modifications and DNA
      hypomethylation. Genes with conserved REST binding are enriched with neural
      functions and more likely to be upregulated upon REST depletion. Interestingly,
      we identified twice as many REST peaks in human ESCs compared to mouse ESCs.
      Human REST cistrome expansion involves additional peaks in genes targeted by REST
      in both species and human-specific gene targets. Genes with expanded REST
      occupancy in humans are enriched for learning or memory functions. Analysis of
      neurological disorder associated genes reveals that Amyotrophic Lateral Sclerosis
      and oxidative stress genes are particularly enriched with human-specific REST
      binding. Overall, our results demonstrate that there is substantial rewiring of
      human and mouse REST cistromes, and that REST may have human-specific roles in
      brain development and functions.

PMID- 25990721
TI  - AP endonuclease 1 prevents trinucleotide repeat expansion via a novel mechanism
      during base excision repair.
AB  - Base excision repair (BER) of an oxidized base within a trinucleotide repeat
      (TNR) tract can lead to TNR expansions that are associated with over 40 human
      neurodegenerative diseases. This occurs as a result of DNA secondary structures
      such as hairpins formed during repair. We have previously shown that BER in a TNR
      hairpin loop can lead to removal of the hairpin, attenuating or preventing TNR
      expansions. Here, we further provide the first evidence that AP endonuclease 1
      (APE1) prevented TNR expansions via its 3'-5' exonuclease activity and
      stimulatory effect on DNA ligation during BER in a hairpin loop. Coordinating
      with flap endonuclease 1, the APE1 3'-5' exonuclease activity cleaves the
      annealed upstream 3'-flap of a double-flap intermediate resulting from 5'
      incision of an abasic site in the hairpin loop. Furthermore, APE1 stimulated DNA
      ligase I to resolve a long double-flap intermediate, thereby promoting hairpin
      removal and preventing TNR expansions. 

PMID- 25990723
TI  - MS2PIP prediction server: compute and visualize MS2 peak intensity predictions
      for CID and HCD fragmentation.
AB  - We present an MS(2) peak intensity prediction server that computes MS(2) charge
      2+ and 3+ spectra from peptide sequences for the most common fragment ions. The
      server integrates the Unimod public domain post-translational modification
      database for modified peptides. The prediction model is an improvement of the
      previously published MS(2)PIP model for Orbitrap-LTQ CID spectra. Predicted MS(2)
      spectra can be downloaded as a spectrum file and can be visualized in the browser
      for comparisons with observations. In addition, we added prediction models for
      HCD fragmentation (Q-Exactive Orbitrap) and show that these models compute
      accurate intensity predictions on par with CID performance. We also show that
      training prediction models for CID and HCD separately improves the accuracy for
      each fragmentation method. The MS(2)PIP prediction server is accessible from
      http://iomics.ugent.be/ms2pip. 

PMID- 25990722
TI  - N protein from lambdoid phages transforms NusA into an antiterminator by
      modulating NusA-RNA polymerase flap domain interactions.
AB  - Interaction of the lambdoid phage N protein with the bacterial transcription
      elongation factor NusA is the key component in the process of transcription
      antitermination. A convex surface of E. coli NusA-NTD, located opposite to its
      RNA polymerase-binding domain (the beta-flap domain), directly interacts with N
      in the antitermination complex. We hypothesized that this N-NusA interaction
      induces allosteric effects on the NusA-RNAP interaction leading to transformation
      of NusA into a facilitator of the antitermination process. Here we showed that
      mutations in beta-flap domain specifically defective for N antitermination
      exhibited altered NusA-nascent RNA interaction and have widened RNA exit channel
      indicating an intricate role of flap domain in the antitermination. The presence
      of N reoriented the RNAP binding surface of NusA-NTD, which changed its
      interaction pattern with the flap domain. These changes caused significant
      spatial rearrangement of the beta-flap as well as the beta' dock domains to form
      a more constricted RNA exit channel in the N-modified elongation complex (EC),
      which might play key role in converting NusA into a facilitator of the N
      antitermination. We propose that in addition to affecting the RNA exit channel
      and the active center of the EC, beta-flap domain rearrangement is also a
      mechanistic component in the N antitermination process. 

PMID- 25990724
TI  - Small RNA-mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to
      aberrant DNA methylation.
AB  - Mammalian cells contain copious amounts of RNA including both coding and
      noncoding RNA (ncRNA). Generally the ncRNAs function to regulate gene expression
      at the transcriptional and post-transcriptional level. Among ncRNA, the long
      ncRNA and small ncRNA can affect histone modification, DNA methylation targeting
      and gene silencing. Here we show that endogenous DNA methyltransferase 1 (DNMT1)
      co-purifies with inhibitory ncRNAs. MicroRNAs (miRNAs) bind directly to DNMT1
      with high affinity. The binding of miRNAs, such as miR-155-5p, leads to
      inhibition of DNMT1 enzyme activity. Exogenous miR-155-5p in cells induces
      aberrant DNA methylation of the genome, resulting in hypomethylation of low to
      moderately methylated regions. And small shift of hypermethylation of previously
      hypomethylated region was also observed. Furthermore, hypomethylation led to
      activation of genes. Based on these observations, overexpression of miR-155-5p
      resulted in aberrant DNA methylation by inhibiting DNMT1 activity, resulting in
      altered gene expression. 

PMID- 25990726
TI  - Multidimensional gene search with Genehopper.
AB  - The high abundance of genetic information enables researchers to gain new
      insights from the comparison of human genes according to their similarities.
      However, existing tools that allow the exploration of such gene-to-gene
      relationships, apply each similarity independently. To make use of
      multidimensional scoring, we developed a new search engine named Genehopper. It
      can handle two query types: (i) the typical use case starts with a term-to-gene
      search, i.e. an optimized full-text search for an anchor gene of interest. The
      web-interface can handle one or more terms including gene symbols and identifiers
      of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined,
      the user can explore its neighborhood by a gene-to-gene search as the weighted
      sum of nine normalized gene similarities based on sequence homology, protein
      domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and
      other features. Each weight can be adjusted by the user, allowing flexible
      customization of the gene search. All implemented similarities have a low
      pairwise correlation (max r(2) = 0.4) implying a low linear dependency, i.e. any
      change in a single weight has an effect on the ranking. Thus, we treated them as
      separate dimensions in the search space. Genehopper is freely available at
      http://genehopper.ifis.cs.tu-bs.de. 

PMID- 25990725
TI  - Cdt1-binding protein GRWD1 is a novel histone-binding protein that facilitates
      MCM loading through its influence on chromatin architecture.
AB  - Efficient pre-replication complex (pre-RC) formation on chromatin templates is
      crucial for the maintenance of genome integrity. However, the regulation of
      chromatin dynamics during this process has remained elusive. We found that a
      conserved protein, GRWD1 (glutamate-rich WD40 repeat containing 1), binds to two
      representative replication origins specifically during G1 phase in a CDC6- and
      Cdt1-dependent manner, and that depletion of GRWD1 reduces loading of MCM but not
      CDC6 and Cdt1. Furthermore, chromatin immunoprecipitation coupled with high
      throughput sequencing (Seq) revealed significant genome-wide co-localization of
      GRWD1 with CDC6. We found that GRWD1 has histone-binding activity. To investigate
      the effect of GRWD1 on chromatin architecture, we used formaldehyde-assisted
      isolation of regulatory elements (FAIRE)-seq or FAIRE-quantitative PCR analyses,
      and the results suggest that GRWD1 regulates chromatin openness at specific
      chromatin locations. Taken together, these findings suggest that GRWD1 may be a
      novel histone-binding protein that regulates chromatin dynamics and MCM loading
      at replication origins. 

PMID- 25990728
TI  - Eukaryotic translation initiation factor eIF5 promotes the accuracy of start
      codon recognition by regulating Pi release and conformational transitions of the
      preinitiation complex.

PMID- 25990727
TI  - APPRIS WebServer and WebServices.
AB  - This paper introduces the APPRIS WebServer (http://appris.bioinfo.cnio.es) and
      WebServices (http://apprisws.bioinfo.cnio.es). Both the web servers and the web
      services are based around the APPRIS Database, a database that presently houses
      annotations of splice isoforms for five different vertebrate genomes. The APPRIS
      WebServer and WebServices provide access to the computational methods implemented
      in the APPRIS Database, while the APPRIS WebServices also allows retrieval of the
      annotations. The APPRIS WebServer and WebServices annotate splice isoforms with
      protein structural and functional features, and with data from cross-species
      alignments. In addition they can use the annotations of structure, function and
      conservation to select a single reference isoform for each protein-coding gene
      (the principal protein isoform). APPRIS principal isoforms have been shown to
      agree overwhelmingly with the main protein isoform detected in proteomics
      experiments. The APPRIS WebServer allows for the annotation of splice isoforms
      for individual genes, and provides a range of visual representations and tools to
      allow researchers to identify the likely effect of splicing events. The APPRIS
      WebServices permit users to generate annotations automatically in high throughput
      mode and to interrogate the annotations in the APPRIS Database. The APPRIS
      WebServices have been implemented using REST architecture to be flexible, modular
      and automatic. 

PMID- 25990729
TI  - Frequency-based haplotype reconstruction from deep sequencing data of bacterial
      populations.
AB  - Clonal populations accumulate mutations over time, resulting in different
      haplotypes. Deep sequencing of such a population in principle provides
      information to reconstruct these haplotypes and the frequency at which the
      haplotypes occur. However, this reconstruction is technically not trivial,
      especially not in clonal systems with a relatively low mutation frequency. The
      low number of segregating sites in those systems adds ambiguity to the haplotype
      phasing and thus obviates the reconstruction of genome-wide haplotypes based on
      sequence overlap information.Therefore, we present EVORhA, a haplotype
      reconstruction method that complements phasing information in the non-empty read
      overlap with the frequency estimations of inferred local haplotypes. As was shown
      with simulated data, as soon as read lengths and/or mutation rates become
      restrictive for state-of-the-art methods, the use of this additional frequency
      information allows EVORhA to still reliably reconstruct genome-wide haplotypes.
      On real data, we show the applicability of the method in reconstructing the
      population composition of evolved bacterial populations and in decomposing mixed
      bacterial infections from clinical samples. 

PMID- 25990730
TI  - Rational evolution of Cd2+-specific DNAzymes with phosphorothioate modified
      cleavage junction and Cd2+ sensing.
AB  - In vitro selection of RNA-cleaving DNAzymes is a powerful method for isolating
      metal-specific DNA. A few successful examples are known, but it is still
      difficult to target some thiophilic metals such as Cd(2+) due to limited
      functional groups in DNA. While using modified bases expands the chemical
      functionality of DNA, a single phosphorothioate modification might boost its
      affinity for thiophilic metals without complicating the selection process or
      using bases that are not commercially available. In this work, the first such in
      vitro selection for Cd(2+) is reported. After using a blocking DNA and negative
      selections to rationally direct the library outcome, a highly specific DNAzyme
      with only 12 nucleotides in the catalytic loop is isolated. This DNAzyme has a
      cleavage rate of 0.12 min(-1) with 10 MUM Cd(2+) at pH 6.0. The Rp form of the
      substrate is cleaved ~100-fold faster than the Sp form. The DNAzyme is most
      active with Cd(2+) and its selectivity against Zn(2+) is over 100 000-fold. Its
      application in detecting Cd(2+) is also demonstrated. The idea of introducing
      single modifications in the fixed region expands the scope of DNA/metal
      interactions with minimal perturbation of DNA structure and property. 

PMID- 25990732
TI  - StarScan: a web server for scanning small RNA targets from degradome sequencing
      data.
AB  - Endogenous small non-coding RNAs (sRNAs), including microRNAs, PIWI-interacting
      RNAs and small interfering RNAs, play important gene regulatory roles in animals
      and plants by pairing to the protein-coding and non-coding transcripts. However,
      computationally assigning these various sRNAs to their regulatory target genes
      remains technically challenging. Recently, a high-throughput degradome sequencing
      method was applied to identify biologically relevant sRNA cleavage sites. In this
      study, an integrated web-based tool, StarScan (sRNA target Scan), was developed
      for scanning sRNA targets using degradome sequencing data from 20 species. Given
      a sRNA sequence from plants or animals, our web server performs an ultrafast and
      exhaustive search for potential sRNA-target interactions in annotated and
      unannotated genomic regions. The interactions between small RNAs and target
      transcripts were further evaluated using a novel tool, alignScore. A novel tool,
      degradomeBinomTest, was developed to quantify the abundance of degradome
      fragments located at the 9-11th nucleotide from the sRNA 5' end. This is the
      first web server for discovering potential sRNA-mediated RNA cleavage events in
      plants and animals, which affords mechanistic insights into the regulatory roles
      of sRNAs. The StarScan web server is available at
      http://mirlab.sysu.edu.cn/starscan/. 

PMID- 25990731
TI  - Genome-wide promoter binding profiling of protein phosphatase-1 and its major
      nuclear targeting subunits.
AB  - Protein phosphatase-1 (PP1) is a key regulator of transcription and is targeted
      to promoter regions via associated proteins. However, the chromatin binding sites
      of PP1 have never been studied in a systematic and genome-wide manner.
      Methylation-based DamID profiling in HeLa cells has enabled us to map hundreds of
      promoter binding sites of PP1 and three of its major nuclear interactors, i.e.
      RepoMan, NIPP1 and PNUTS. Our data reveal that the alpha, beta and gamma isoforms
      of PP1 largely bind to distinct subsets of promoters and can also be
      differentiated by their promoter binding pattern. PP1beta emerged as the major
      promoter-associated isoform and shows an overlapping binding profile with PNUTS
      at dozens of active promoters. Surprisingly, most promoter binding sites of PP1
      are not shared with RepoMan, NIPP1 or PNUTS, hinting at the existence of
      additional, largely unidentified chromatin-targeting subunits. We also found that
      PP1 is not required for the global chromatin targeting of RepoMan, NIPP1 and
      PNUTS, but alters the promoter binding specificity of NIPP1. Our data disclose an
      unexpected specificity and complexity in the promoter binding of PP1 isoforms and
      their chromatin-targeting subunits. 

PMID- 25990733
TI  - Removing unwanted variation in a differential methylation analysis of Illumina
      HumanMethylation450 array data.
AB  - Due to their relatively low-cost per sample and broad, gene-centric coverage of
      CpGs across the human genome, Illumina's 450k arrays are widely used in large
      scale differential methylation studies. However, by their very nature, large
      studies are particularly susceptible to the effects of unwanted variation. The
      effects of unwanted variation have been extensively documented in gene expression
      array studies and numerous methods have been developed to mitigate these effects.
      However, there has been much less research focused on the appropriate methodology
      to use for accounting for unwanted variation in methylation array studies. Here
      we present a novel 2-stage approach using RUV-inverse in a differential
      methylation analysis of 450k data and show that it outperforms existing methods. 

PMID- 25990734
TI  - Mutations in the CRE pocket of bacterial RNA polymerase affect multiple steps of
      transcription.
AB  - During transcription, the catalytic core of RNA polymerase (RNAP) must interact
      with the DNA template with low-sequence specificity to ensure efficient enzyme
      translocation and RNA extension. Unexpectedly, recent structural studies of
      bacterial promoter complexes revealed specific interactions between the
      nontemplate DNA strand at the downstream edge of the transcription bubble (CRE,
      core recognition element) and a protein pocket formed by core RNAP (CRE pocket).
      We investigated the roles of these interactions in transcription by analyzing
      point amino acid substitutions and deletions in Escherichia coli RNAP. The
      mutations affected multiple steps of transcription, including promoter
      recognition, RNA elongation and termination. In particular, we showed that
      interactions of the CRE pocket with a nontemplate guanine immediately downstream
      of the active center stimulate RNA-hairpin-dependent transcription pausing but
      not other types of pausing. Thus, conformational changes of the elongation
      complex induced by nascent RNA can modulate CRE effects on transcription. The
      results highlight the roles of specific core RNAP-DNA interactions at different
      steps of RNA synthesis and suggest their importance for transcription regulation
      in various organisms. 

PMID- 25990735
TI  - MyProteinNet: build up-to-date protein interaction networks for organisms,
      tissues and user-defined contexts.
AB  - The identification of the molecular pathways active in specific contexts, such as
      disease states or drug responses, often requires an extensive view of the
      potential interactions between a subset of proteins. This view is not easily
      obtained: it requires the integration of context-specific protein list or
      expression data with up-to-date data of protein interactions that are typically
      spread across multiple databases. The MyProteinNet web server allows users to
      easily create such context-sensitive protein interaction networks. Users can
      automatically gather and consolidate data from up to 11 different databases to
      create a generic protein interaction network (interactome). They can score the
      interactions based on reliability and filter them by user-defined contexts
      including molecular expression and protein annotation. The output of MyProteinNet
      includes the generic and filtered interactome files, together with a summary of
      their network attributes. MyProteinNet is particularly geared toward building
      human tissue interactomes, by maintaining tissue expression profiles from
      multiple resources. The ability of MyProteinNet to facilitate the construction of
      up-to-date, context-specific interactomes and its applicability to 11 different
      organisms and to tens of human tissues, make it a powerful tool in meaningful
      analysis of protein networks. MyProteinNet is available at
      http://netbio.bgu.ac.il/myproteinnet. 

PMID- 25990736
TI  - SLX4 contributes to telomere preservation and regulated processing of telomeric
      joint molecule intermediates.
AB  - SLX4 assembles a toolkit of endonucleases SLX1, MUS81 and XPF, which is recruited
      to telomeres via direct interaction of SLX4 with TRF2. Telomeres present an
      inherent obstacle for DNA replication and repair due to their high propensity to
      form branched DNA intermediates. Here we provide novel insight into the mechanism
      and regulation of the SLX4 complex in telomere preservation. SLX4 associates with
      telomeres throughout the cell cycle, peaking in late S phase and under genotoxic
      stress. Disruption of SLX4's interaction with TRF2 or SLX1 and SLX1's nuclease
      activity independently causes telomere fragility, suggesting a requirement of the
      SLX4 complex for nucleolytic resolution of branched intermediates during telomere
      replication. Indeed, the SLX1-SLX4 complex processes a variety of telomeric joint
      molecules in vitro. The nucleolytic activity of SLX1-SLX4 is negatively regulated
      by telomeric DNA-binding proteins TRF1 and TRF2 and is suppressed by the RecQ
      helicase BLM in vitro. In vivo, in the presence of functional BLM, telomeric
      circle formation and telomere sister chromatid exchange, both arising out of
      nucleolytic processing of telomeric homologous recombination intermediates, are
      suppressed. We propose that the SLX4-toolkit is a telomere accessory complex
      that, in conjunction with other telomere maintenance proteins, ensures
      unhindered, but regulated telomere maintenance. 

PMID- 25990737
TI  - Nicked-site substrates for a serine recombinase reveal enzyme-DNA communications
      and an essential tethering role of covalent enzyme-DNA linkages.
AB  - To analyse the mechanism and kinetics of DNA strand cleavages catalysed by the
      serine recombinase Tn3 resolvase, we made modified recombination sites with a
      single-strand nick in one of the two DNA strands. Resolvase acting on these sites
      cleaves the intact strand very rapidly, giving an abnormal half-site product
      which accumulates. We propose that these reactions mimic second-strand cleavage
      of an unmodified site. Cleavage occurs in a synapse of two sites, held together
      by a resolvase tetramer; cleavage at one site stimulates cleavage at the partner
      site. After cleavage of a nicked-site substrate, the half-site that is not
      covalently linked to a resolvase subunit dissociates rapidly from the synapse,
      destabilizing the entire complex. The covalent resolvase-DNA linkages in the
      natural reaction intermediate thus perform an essential DNA-tethering function.
      Chemical modifications of a nicked-site substrate at the positions of the
      scissile phosphodiesters result in abolition or inhibition of resolvase-mediated
      cleavage and effects on resolvase binding and synapsis, providing insight into
      the serine recombinase catalytic mechanism and how resolvase interacts with the
      substrate DNA. 

PMID- 25990738
TI  - A low-latency, big database system and browser for storage, querying and
      visualization of 3D genomic data.
AB  - Recent releases of genome three-dimensional (3D) structures have the potential to
      transform our understanding of genomes. Nonetheless, the storage technology and
      visualization tools need to evolve to offer to the scientific community fast and
      convenient access to these data. We introduce simultaneously a database system to
      store and query 3D genomic data (3DBG), and a 3D genome browser to visualize and
      explore 3D genome structures (3DGB). We benchmark 3DBG against state-of-the-art
      systems and demonstrate that it is faster than previous solutions, and
      importantly gracefully scales with the size of data. We also illustrate the
      usefulness of our 3D genome Web browser to explore human genome structures. The
      3D genome browser is available at http://3dgb.cs.mcgill.ca/. 

PMID- 25990739
TI  - ATP-dependent G-quadruplex unfolding by Bloom helicase exhibits low processivity.
AB  - Various helicases and single stranded DNA (ssDNA) binding proteins unfold G
      quadruplex (GQ) structures. However, the underlying mechanisms of this activity
      have only recently come to focus. We report kinetic studies on Bloom (BLM)
      helicase and human telomeric GQ interactions using single-molecule Forster
      resonance energy transfer (smFRET). Using partial duplex DNA (pdDNA) constructs
      with different 5' ssDNA overhangs, we show that BLM localizes in the vicinity of
      ssDNA/double-stranded DNA (dsDNA) junction and reels in the ssDNA overhang in an
      ATP-dependent manner. A comparison of DNA constructs with or without GQ in the
      overhang shows that GQ unfolding is achieved in 50-70% of reeling attempts under
      physiological salt and pH conditions. The unsuccessful attempts often result in
      dissociation of BLM from DNA which slows down the overall BLM activity. BLM
      mediated GQ unfolding is typically followed by refolding of the GQ, a pattern
      that is repeated several times before BLM dissociates from DNA. BLM is
      significantly less processive compared to the highly efficient GQ destabilizer
      Pif1 that can repeat GQ unfolding activity hundreds of times before dissociating
      from DNA. Despite the variations in processivity, our studies point to possible
      common patterns used by different helicases in minimizing the duration of stable
      GQ formation. 

PMID- 25990740
TI  - Splicing of a non-coding antisense transcript controls LEF1 gene expression.
AB  - In this report we have analyzed the role of antisense transcription in the
      control of LEF1 transcription factor expression. A natural antisense transcript
      (NAT) is transcribed from a promoter present in the first intron of LEF1 gene and
      undergoes splicing in mesenchymal cells. Although this locus is silent in
      epithelial cells, and neither NAT transcript nor LEF1 mRNA are expressed, in cell
      lines with an intermediate epithelial-mesenchymal phenotype presenting low LEF1
      expression, the NAT is synthesized and remains unprocessed. Contrarily to the
      spliced NAT, this unspliced NAT down-regulates the main LEF1 promoter activity
      and attenuates LEF1 mRNA transcription. Unspliced LEF1 NAT interacts with LEF1
      promoter and facilitates PRC2 binding to the LEF1 promoter and trimethylation of
      lysine 27 in histone 3. Expression of the spliced form of LEF1 NAT in trans
      prevents the action of unspliced NAT by competing for interaction with the
      promoter. Thus, these results indicate that LEF1 gene expression is attenuated by
      an antisense non-coding RNA and that this NAT function is regulated by the
      balance between its spliced and unspliced forms. 

PMID- 25990741
TI  - An implementation of the Gillespie algorithm for RNA kinetics with logarithmic
      time update.
AB  - In this paper I outline a fast method called KFOLD for implementing the Gillepie
      algorithm to stochastically sample the folding kinetics of an RNA molecule at
      single base-pair resolution. In the same fashion as the KINFOLD algorithm, which
      also uses the Gillespie algorithm to predict folding kinetics, KFOLD
      stochastically chooses a new RNA secondary structure state that is accessible
      from the current state by a single base-pair addition/deletion following the
      Gillespie procedure. However, unlike KINFOLD, the KFOLD algorithm utilizes the
      fact that many of the base-pair addition/deletion reactions and their
      corresponding rates do not change between each step in the algorithm. This allows
      KFOLD to achieve a substantial speed-up in the time required to compute a
      prediction of the folding pathway and, for a fixed number of base-pair moves,
      performs logarithmically with sequence size. This increase in speed opens up the
      possibility of studying the kinetics of much longer RNA sequences at single base
      pair resolution while also allowing for the RNA folding statistics of smaller RNA
      sequences to be computed much more quickly. 

PMID- 25990742
TI  - Safety and efficacy of lesion preparation with the AngioSculpt Scoring Balloon in
      left main interventions: the ALSTER Left Main registry.
AB  - AIMS: Left main interventions require optimal initial results for good clinical
      outcome. Lesion preparation with the AngioSculpt Scoring Balloon (ASB) combined
      with the provisional T-stenting technique, if proven safe, might lead to better
      lumen gain and better clinical outcome. The aim of this registry was to
      investigate the safety and efficacy of the ASB as an option for lesion
      preparation in unprotected left main interventions (ULMI). METHODS AND RESULTS:
      Out of the all-comers unprotected left main registry (ULMI ALSTER), 47 patients
      with elective ULMI fulfilled the inclusion criteria for this study. The endpoints
      were acute lumen gain and 12-month MACCE. The drop-out rate was 4%. The
      provisional T-stenting technique was used in 97% of distal ULMI. The
      interventions were grouped according to use of ASB with an in-house, historical
      no-ASB patient control group. Lumen gain was 1.63+/-0.12 mm in the ASB group
      (n=34) and 1.35+/-0.12 mm in the no-ASB group (n=8, p=0.26), respectively. The
      use of the ASB was safe. Intravascular ultrasound (IVUS) data for 21 patients
      showed numerically greater lumen area gain of 3.14+/-0.33 mm2 in the ASB group
      compared to 2.33+/-0.88 mm2 with the conventional technique. TLR/TVR was 6.6%
      overall. Twelve-month MACCE was 12.5% (4/32) for ASB and 15.4% (2/13) in the
      historical control group. CONCLUSIONS: Adding ASB lesion preparation to the
      standard provisional T-stenting technique for ULMI is feasible and safe. Low TLR
      and TVR rates were observed. Lesion preparation led to a numerically larger lumen
      gain; the data allow valid power statistics to show this approach as leading to
      improved outcome in a possible randomised trial.

PMID- 25990744
TI  - Measuring pharmacogenetics in special groups: geriatrics.
AB  - INTRODUCTION: The cytochrome P450 (CYP) enzymes oxidize about 80% of the most
      commonly used drugs. Older patients form a very interesting clinical group in
      which an increased prevalence of adverse drug reactions (ADRs) and therapeutic
      failures (TFs) is observed. Might CYP drug metabolism change with age, and
      justify the differences in drug response observed in a geriatric setting? AREAS
      COVERED: A complete overview of the CYP pharmacogenetics with a focus on the
      epigenetic CYP gene regulation by DNA methylation in the context of advancing
      age, in which DNA methylation might change. EXPERT OPINION: Responder phenotypes
      consist of a continuum spanning from ADRs to TFs, with the best responders at the
      midpoint. CYP genetics is the basis of this continuum on which environmental and
      physiological factors act, modeling the phenotype observed in clinical practice.
      Physiological age-related changes in DNA methylation, the main epigenetic
      mechanisms regulating gene expression in humans, results in a physiological
      decrease in CYP gene expression with advancing age. This may be one of the
      physiological changes that, together with increased drug use, contributed to the
      higher prevalence of ADRs and TFs observed in the geriatric setting, thus, making
      geriatrics a special group for pharmacogenetics.

PMID- 25990745
TI  - US navy will not discharge nurse who refused to force feed Guantanamo prisoners.

PMID- 25990746
TI  - Biannual otolith-zone formation of young shallow-water hake Merluccius capensis
      in the northern Benguela: age verification using otoliths sampled by a top
      predator.
AB  - Otoliths collected at least monthly from scat samples of Cape fur seals
      Arctocephalus pusillus are used to show that shallow-water hake Merluccius
      capensis from the northern Benguela develop three translucent zones in their
      first 1.5 years of life. The novel sampling approach provided otoliths that
      belonged to four M. capensis cohorts of approximate known age (hatched in 1996,
      1998, 2002 and 2005), allowing age verification. Following spawning in austral
      winter, translucent zones consistently formed first in summer and autumn (T1),
      then in winter and spring (T2) and again in summer and autumn (T3), with no
      difference in appearance of the zones (biannuli) for the four cohorts considered.
      The second translucent zone is usually the first true annulus (year mark). It
      forms during July to September in fish of 15-20 cm total length (LT ). Formation
      of the translucent zones appears to be determined by fish length or age, rather
      than by exogenous cues. It is suggested that length measurements should be used
      to help determine the first age group; fish with a translucent zone marked at
      otolith lengths >7.5 mm should be termed 1 year-old fish. Ages of M. capensis
      used in previous stock assessment models have been overestimated. Biannuli are an
      unusual occurrence in fish otoliths in general, but have been observed in other
      Merluccius species. 

PMID- 25990743
TI  - Update on blood pressure control and renal outcomes in diabetes mellitus.
AB  - Diabetic nephropathy (DN) is associated with a high incidence of cardiovascular
      (CV) morbidity and mortality. Although relationships between hypertension and
      diabetic nephropathy are complex, blood pressure (BP) control is an important
      management strategy in the prevention of onset and progression of DN in patients
      with diabetes mellitus (DM). Recent guidelines recommend less stringent BP
      targets among patients with type 2 DM and chronic kidney disease. These
      recommendations are based mostly on lack of benefit in CV outcomes with a low BP
      target. We review the current information on efficacy of BP control in improving
      renal outcomes in patients with type 2 DM. Presently, although intensive BP
      control has been was beneficial in decreasing albuminuria, it has not translated
      into reductions in risks of hard renal endpoints, such as progression to end
      stage renal disease, the need for renal replacement therapy, and mortality from
      renal causes. 

PMID- 25990748
TI  - Inquiry in bioethics and the philosophy of medicine: organ donation, defining
      death, and fairness in distribution.
AB  - This issue of the Journal of Medicine and Philosophy brings together fresh essays
      addressing three main genres of questions: (1) questions about the nature of
      bioethical inquiry and the relevance of the humanities to medical practice; (2)
      questions regarding the ethics of organ donation; (3) questions bearing on the
      application of fairness to the distribution of medical resources. 

PMID- 25990747
TI  - Associations of antibodies against citrullinated peptides with human leukocyte
      antigen-shared epitope and smoking prior to the development of rheumatoid
      arthritis.
AB  - INTRODUCTION: It has previously been shown that an increased number of antibodies
      against citrullinated peptides/proteins (ACPA) predate the onset of rheumatoid
      arthritis (RA). Over time antibody positivity expands, involving more specific
      responses when approaching the onset of symptoms. We investigated the impact of
      human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking on the
      development of ACPA, as well as in combination with ACPA during the state of
      quiescent autoimmunity (before the onset of symptoms), on the development of RA.
      METHODS: Blood samples donated to the Medical Biobank of Northern Sweden from
      individuals prior to the onset of symptoms of RA (n=370) and after onset (n=203)
      and from population-based controls (n=585) were used. Antibodies against 10
      citrullinated peptides, fibrinogen (Fibalpha561-583, alpha580-600, beta62-81a,
      beta62-81b, beta36-52), vimentin (Vim2-17, 60-75), filaggrin (CCP-1/Fil307-324),
      alpha-enolase (CEP-1/Eno5-21), collagen type II (citC1359-369), and anti-cyclic
      citrullinated peptide (CCP)2 antibodies were analysed. RESULTS: HLA-SE-positive
      individuals were more frequently positive for ACPA compared with HLA-SE-negative
      individuals prior to the onset of symptoms of RA, particularly for antibodies
      against CEP-1 and Fibbeta62-81a (72). Smoking was associated with antibodies
      against Vim2-17 and citC1359-369. HLA-SE and smoking showed increasing
      association to the presence of the antibodies closer to disease onset. The
      highest odds ratio (OR) for development of RA was for the combination of HLA-SE
      alleles and ACPA positivity, especially for antibodies against Fibbeta62-81b, CCP
      1/Fil307-324, and Fibbeta36-52. A gene-environment additive interaction between
      smoking and HLA-SE alleles for the risk of disease development was found, with
      the highest OR for individuals positive for antibodies against Fibbeta36-52, CEP
      1, and Fibalpha580-600. CONCLUSIONS: The relationships between antibodies against
      the different ACPA specificities, HLA-SE, and smoking showed a variable pattern
      in individuals prior to the onset of RA. The combination of smoking and HLA-SE
      alleles was significantly associated with the development of some of the antibody
      specificities closer to onset of symptoms, and these associations remained
      significant at diagnosis. An additive gene-environment interaction was found for
      several of the antibodies for the development of RA.

PMID- 25990749
TI  - Citizenship: bioethics and the duties of teachers.

PMID- 25990754
TI  - Sasang constitution affects the prevalence of functional dyspepsia.
AB  - BACKGROUND: Functional dyspepsia (FD), which is a very common disorder worldwide,
      is known to be caused by multiple factors including environmental and genetic
      factors. Sasang constitutional medicine (SCM) is a component of traditional
      Korean medicine that emphasizes inherited characteristics of the physical and
      psychological patterns of a patient. This study investigated whether the
      prevalence of FD differs depending on Sasang classification. METHODS: A total 517
      subjects (190 males and 327 females) were recruited, and interviewed for the
      presence of FD using a Rome III-based questionnaire. The Sasang constitution of
      all subjects were diagnosed using a Sasang constitutional analytical tool (SCAT).
      A Chi-square test was performed to compare prevalence of DF among different
      Sasang constitutional types. RESULTS: Of the 517 subjects, 115 (22.2 %) met the
      diagnostic criteria for FD, and the prevalence was significantly higher in
      females (26.9 %) than males (14.2 %, p < 0.01). The Sasang-constitution-based
      prevalence among all subjects was 27.5 % for Taeumin, 23.1 % for Soumin, and 16.4
      % for Soyangin (p = 0.055). When compared by sex, the prevalence of FD among
      Sasang types showed significantly different patterns between males and females (p
      < 0.05); in females with FD, Taeumin predominated (32.5 % compared with 29.5 %
      and 18.8 % for Soumin and Soyangin, respectively; p < 0.05), whereas males with
      FD displayed a higher prevalence of Soumin (17.3 % compared with 9.1 % and 11.3 %
      for Taeumin and Soyangin, respectively; p > 0.05). CONCLUSIONS: This study
      identified significant differences in FD prevalence depending on Sasang
      constitution and sex. Our findings provide data to guide future research on the
      prevention and management of FD.

PMID- 25990755
TI  - Review of paediatric cardiology services in district general hospitals in the
      United Kingdom.
AB  - Following the Safe and Sustainable review of Paediatric Services in 2012/2013,
      National Health Service England recommended that local paediatric cardiology
      services should be provided by specially trained paediatricians with expertise in
      cardiology in all non-specialist hospitals. AIM: To understand the variation in
      local paediatric cardiology services provided across district general hospitals
      in the United Kingdom. STUDY DESIGN AND METHODS: An internet-based questionnaire
      was sent out via the Paediatrician with Expertise in Cardiology Special Interest
      Group and the Neonatologists with Interest in Cardiology and Haemodynamics
      contact databases and the National Health Service directory. Non-responders were
      followed-up via telephone. RESULTS: The response rate was 80% (141 of 177
      hospitals), and paediatricians with expertise in cardiology were available in 68%
      of those. Local cardiology clinics led by paediatricians with expertise in
      cardiology were provided in 96 hospitals (68%), whereas specialist outreach
      clinics were held in 123 centres (87%). A total of 11 hospitals provided neither
      specialist outreach clinics nor any local cardiology clinics led by
      paediatricians with expertise in cardiology. Paediatric echocardiography services
      were provided in 83% of the hospitals, 12-lead electrocardiogram in 96%, Holter
      electrocardiogram in 91%, and exercise testing in only 47% of the responding
      hospitals. Telemedicine facilities were established in only 52% of the centres,
      where sharing echocardiogram images via picture archiving and communication
      system was used most commonly. CONCLUSION: There has been a substantial increase
      in the availability of paediatricians with expertise in cardiology since 2008.
      Most of the hospitals are well-supported by specialist cardiology centres via
      outreach clinics; however, there remains significant variation in the local
      paediatric cardiology services provided across district general hospitals in the
      United Kingdom.

PMID- 25990756
TI  - A UPLC-MS Method for Simultaneous Determination of Geniposidic Acid, Two Lignans
      and Phenolics in Rat Plasma and its Application to Pharmacokinetic Studies of
      Eucommia ulmoides Extract in Rats.
AB  - The bark of Eucommia ulmoides is a well-known Chinese herbal medicine that is
      used to regulate blood pressure and reduce blood sugar and fats, as well as an
      antioxidant and antimicrobial agent. Here we describe the development of a
      sensitive ultrahigh performance liquid chromatography-tandem mass spectrum method
      for the simultaneous determination of five major active ingredients of E.
      ulmoides bark extract, namely, geniposidic acid (GA), protocatechuic acid (PCA),
      chlorogenic acid (CA), (+)-pinoresinol di-O-beta-D-glucopyranoside (PDG) and (+)
      pinoresinol 4'-O-beta-D-glucopyranoside (PG), in rat plasma. The preliminary
      steps in the plasma analysis were the addition of an internal standard and
      acidification (0.1 % formic acid), followed by protein precipitation with
      methanol. Separation of the active ingredients was performed on an ACQUITY
      UPLC(r) BEH C18 column (2.1 * 50 mm; internal diameter 1.7 um) at a flow rate of
      0.35 mL/min, with acetonitrile/water containing 0.1 % formic acid as the mobile
      phase. Detection was performed on a triple quadrupole tandem mass spectrometer
      via electrospray ionization source with positive and negative ionization modes.
      All calibration curves showed good linearity (r >= 0.997) over the concentration
      range with the low limit of quantification between 4.45 and 54.9 ng/mL. Precision
      was evaluated by intra- and inter-day assays, and the percentages of the relative
      standard deviation were all within 15 %. Extraction efficiency and matrix effect
      were 84.3-102.4 % and 98.1-112.2 %, respectively. The validated method was
      successfully applied to the pharmacokinetic study in rats after oral
      administration of E. ulmoides extract. The results indicate that the
      pharmacokinetic properties of GA differ from those of PCA, CA, PDG and PG,
      respectively. 

PMID- 25990757
TI  - A Method of Effectively Improved alpha-Mangostin Bioavailability.
AB  - alpha-Mangostin, a major xanthone isolated from the pericarp of Garcinia
      mangostana, exhibits anti-inflammatory and antitumor effects. Its absolute
      bioavailability is low, with minimal oral absorption. In this article, a soft
      capsule, with vegetable oil as the dispersion matrix, was prepared to improve the
      bioavailability of alpha-mangostin. Its pharmacokinetics and tissue distribution
      were determined in rats. An HPLC assay was established to determine the
      concentration of alpha-mangostin in biological samples. The validated method was
      used successfully to support pharmacokinetic and tissue distribution studies of
      alpha-mangostin in rats after intravenous (i.v.) and oral administration. The
      pharmacokinetic study found the absolute bioavailabilities of low, medium and
      high doses were 61.1, 51.5 and 42.5 %, respectively, indicating that the absolute
      bioavailability was effectively improved. 

PMID- 25990758
TI  - Recreational football is effective in the treatment of non-communicable diseases.

PMID- 25990759
TI  - The search for size: a doping risk factor in adolescent rugby?

PMID- 25990760
TI  - Frequency preference in cervical vestibular evoked myogenic potential of
      idiopathic otolithic vertigo patients. Does it reflect otolithic endolymphatic
      hydrops?
AB  - CONCLUSION: Idiopathic otolithic vertigo (IOV) with relatively long duration of
      attacks might be caused by endolymphatic hydrops in the otolith organ.
      OBJECTIVES: To clarify the pathophysiology underlying IOV, episodic tilting or
      translational sensation attacks by unknown causes, especially the possibility of
      endolymphatic hydrops in the otolith organ. METHODS: Sixteen patients (6 men and
      10 women) diagnosed with having IOV were enrolled. In these subjects, frequency
      preference in cervical vestibular evoked myogenic potential (cVEMP) was studied.
      The subjects underwent cVEMP testing using 500 Hz and 1000 Hz short tone bursts
      (STB) (125 dB SPL, air-conducted sound). The 500-1000 Hz cVEMP slope was
      calculated and assessed in comparison with data from healthy subjects in the
      preceding study. RESULTS: Twelve of the 16 examined patients had a significant
      preference of 1000 Hz to 500 Hz, which was suggestive of endolymphatic hydrops in
      the saccule. Patients with frequency preference of 1000 Hz to 500 Hz showed a
      tendency for longer vertigo attacks than patients without preference of 1000 Hz.

PMID- 25990761
TI  - Novel Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis
      Inhibitor (TAFIa) from Natural Product Anabaenopeptin.
AB  - Anabaenopeptins isolated from cyanobacteria were identified as inhibitors of
      carboxypeptidase TAFIa. Cocrystal structures of these macrocyclic natural product
      inhibitors in a modified porcine carboxypeptidase B revealed their binding mode
      and provided the basis for the rational design of small molecule inhibitors with
      a previously unknown central urea motif. Optimization based on these design
      concepts allowed for a rapid evaluation of the SAR and delivered potent small
      molecule inhibitors of TAFIa with a promising overall profile. 

PMID- 25990762
TI  - Assisting Undergraduate Physician Assistant Training in Psychiatry: The Role of
      Academic Psychiatry Departments.
AB  - Physician assistants (PAs) are medical professionals who practice medicine with
      the supervision of a physician through delegated autonomy. PA school
      accreditation standards provide limited guidance for training PAs in psychiatry.
      As a result, PA students may receive inconsistent and possibly inadequate
      exposure to psychiatry. Providing broad and in-depth exposure to the field of
      psychiatry is important to attract PA students to pursue careers in psychiatry
      and provide a possible solution to the shortage of psychiatrists nationwide.
      Additionally, this level of exposure will prepare PA students who pursue careers
      in other fields of medicine to recognize and address their patient's psychiatric
      symptoms in an appropriate manner. This training can be provided by an academic
      department of psychiatry invested in the education of PA students. We describe a
      training model implemented at our university that emphasizes psychiatrist
      involvement in the preclinical year of PA school and full integration of PA
      students into the medical student psychiatry clerkship during the clinical years.
      The benefits and challenges to implementing this model are discussed as well. 

PMID- 25990763
TI  - Reply: To PMID 25045167.

PMID- 25990764
TI  - Boosting multi-state models.
AB  - One important goal in multi-state modelling is to explore information about
      conditional transition-type-specific hazard rate functions by estimating
      influencing effects of explanatory variables. This may be performed using single
      transition-type-specific models if these covariate effects are assumed to be
      different across transition-types. To investigate whether this assumption holds
      or whether one of the effects is equal across several transition-types (cross
      transition-type effect), a combined model has to be applied, for instance with
      the use of a stratified partial likelihood formulation. Here, prior knowledge
      about the underlying covariate effect mechanisms is often sparse, especially
      about ineffectivenesses of transition-type-specific or cross-transition-type
      effects. As a consequence, data-driven variable selection is an important task: a
      large number of estimable effects has to be taken into account if joint modelling
      of all transition-types is performed. A related but subsequent task is model
      choice: is an effect satisfactory estimated assuming linearity, or is the true
      underlying nature strongly deviating from linearity? This article introduces
      component-wise Functional Gradient Descent Boosting (short boosting) for multi
      state models, an approach performing unsupervised variable selection and model
      choice simultaneously within a single estimation run. We demonstrate that
      features and advantages in the application of boosting introduced and illustrated
      in classical regression scenarios remain present in the transfer to multi-state
      models. As a consequence, boosting provides an effective means to answer
      questions about ineffectiveness and non-linearity of single transition-type
      specific or cross-transition-type effects. 

PMID- 25990766
TI  - Metal-Free, Acid-Catalyzed ortho-Directed Synthesis of Anthranilic Acid
      Derivatives Using Carbodiimides.
AB  - One-pot syntheses of fluorescent o-aminobenzoates, o-aminopyridine carboxylates,
      and a 2'-amino-[1,1'-biphenyl]-2-carboxylic acid are described. Carbodiimides are
      used as the source of the 2-amino function which inserts onto an aromatic ring
      using S(N)Ar reaction conditions. This method proceeds regiospecifically with a
      range of 2-fluoroaromatic acids or esters bearing further aryl fluorine,
      trifluoromethyl, and cyano substituents.

PMID- 25990765
TI  - Application of hyaluronic acid/sodium alginate-based microparticles to prevent
      tissue adhesion in a rabbit model.
AB  - PURPOSE: Postsurgical adhesion formation is a concern in every field of surgery.
      We evaluated the efficacy of hyaluronic acid/sodium alginate-based microparticle
      anti-adhesive agents (MP) for the prevention of postsurgical adhesion formation
      in a standardized rabbit model. METHOD: To evaluate the anti-adhesion effect, a
      uterus-abdominal wall abrasion model was created in rabbits. On the surface of
      the injured uterus, an anti-adhesive agent, Interceed((r)) or MP, was applied
      (positive control and study groups, respectively; n = 10 each). In another group
      of 10 animals, neither agent was applied (negative control group). The adhesion
      levels were graded 3 weeks after surgery. Acute and chronic toxicity was also
      evaluated. RESULTS: The grade of adhesion was significantly lower in the MP group
      than in the negative control and positive control groups. No evidence of acute or
      chronic toxicity induced by this material was found in blood and tissue analysis.
      CONCLUSION: MP shows potential as an effective novel type of resorbable
      biomaterial to reduce postoperative adhesion. The easy placement and handling of
      this material make the MP powder attractive as a tissue adhesion barrier.

PMID- 25990767
TI  - A morphological study of the normally aging heart.
AB  - A morphological examination of aging was performed on 141 normal hearts selected
      from a total of 972 consecutive autopsies on persons aged 60 years or over. The
      average heart weight was 270 +/- 41 g. The circumference of the valvular ring was
      99 +/- 10 mm in the tricuspid valve, 68 +/- 8 mm in the pulmonic valve, 83 +/- 10
      mm in the mitral valve, and 73 +/- 7 mm in the aortic valve. The thickness of the
      tricuspid valve (anterior leaflet) was 0.9 +/- 0.3 mm, pulmonic (anterior cusp)
      0.4 +/- 0.3 mm, mitral (anterior leaflet) 1.3 +/- 0.6 mm, and aortic (posterior
      cusp) 1.0 +/- 0.6 mm. Cardiac chamber volumes were as follows: 40 +/- 14 mL in
      the right atrium, 22 +/- 7 mL in the right ventricle, 37 +/- 12 mL in the left
      atrium, and 7.3 +/- 3.4 mL in the left ventricle. The circumference of the
      tricuspid ring was the largest. Left-sided valves were thicker than right-sides
      valves, and atrioventricular valves were thicker than semilunar valves. Cardiac
      chamber volumes were generally larger on the right side. Because this study was
      limited to hearts from persons aged 60 years or over, age-related changes were
      observed in only four parameters: (i) the circumference of the aortic valvular
      ring, (ii) the thickness of the aortic posterior cusp, (iii) the thickness of the
      pulmonic anterior cusp, and (iv) the volume of the left ventricle. With
      increasing age the aortic valvular ring dilated, the aortic posterior cusp and
      the pulmonic anterior cusp thickened, and the left ventricular volume diminished.

PMID- 25990768
TI  - Histologic characterization of carotid plaques.
AB  - From January 1988 to December 1989, we performed a total of 278 carotid
      thromboendarterectomies. The plaque was systematically prepared for
      anatomicopathological analysis by standard light microscopic techniques. We
      sought to correlate the histology of the endarterectomy specimen with the
      clinical data. Twenty-eight plaques were not suitable for analysis and
      classification. The remaining 250 plaques were subdivided as 216 (86%)
      complicated plaques and 34 (14%) simple fibrous plaques. In the complicated
      plaques, one or more of the following pathologic characteristics were described:
      organized intraplaque hematoma (observed in 115 plaques), fresh thrombus (50),
      ulceration (92), and recent intraplaque hemorrhage (168). Fifty-three percent of
      these complicated plaques were symptomatic with corresponding neurologic deficit
      (amaurosis, transient ischemic attacks, reversible ischemic neurologic deficit,
      or stroke), compared with 21% of the simple plaques (p < 0.001). With regard (o
      plaque characteristics, the only significant clinicopathologic correlation was
      found for plaques with fresh thrombus, which were symptomatic in 70% of cases,
      and for ulcerated plaques (symptomatic in 66% of cases). This comparative study
      provides no significant evidence of increased predisposition to neurologic
      deficit for the other morphological aspects (intraplaque hemorrhage, healed
      ulceration, organized hematoma). We conclude that plaque morphology, rather than
      luminal narrowing, plays a primary role in cerebral ischemic disease. 

PMID- 25990769
TI  - The role of ventricular wall stress in cardiac hypertrophy.
AB  - This study tested the hypothesis that stable cardiac disease occurs when
      hypertrophy is sufficient to normalize wall stress imposed by a hemodynamic load
      and that cardiac decompensation occurs when wall stress becomes abnormal as the
      limit of the hypertrophic process is reached. Toward this end, comprehensive
      stress analysis of the left ventricle was performed on 46 autopsy heart specimens
      constituting three groups: normal control, concentric left ventricular
      hypertrophy, and eccentric left ventricular hypertrophy. Our analytical method
      took into account the effect of residual stress on the total stress distribution
      and represented an approach to stress analysis of the left ventricle that is more
      accurate than the conventional approach. The stress gradient in the left
      ventricular wall attributable to pressure alone showed very high values in all
      three groups according to the conventional model. Using our newly developed
      model, the resultant stress gradients attributable to the superimposed residual
      stress were much lower. There was a significant association between clinical
      cardiac decompensation and both maximum resultant stress (p < 0.005) and
      resultant stress gradient (p < 0.05). We also found close association between
      cardiac decompensation and heart weight (p < 0.0015). Furthermore, maximum
      resultant stress showed a close correlation with heart weight (p < 0.025).
      Maximum resultant stress in the eccentric hypertrophy group was higher than that
      in the other groups (p < 0.0015). The results from this study indicate that the
      left ventricular wall stress is closely correlated with left ventricular
      performance and is a good predictor of chronic cardiac failure. 

PMID- 25990770
TI  - Frequency, extent, and distribution of endomyocardial adipose tissue:
      Morphometric analysis of endomyocardial biopsy specimens from 241 patients.
AB  - Features of endomyocardial biopsy specimens (EMB) have been analyzed extensively;
      however, the frequency, distribution, and associations of adipose tissue in EMB
      taken from patients with failing hearts have received less attention. We analyzed
      morphologically and morphometrically EMB from 241 patients (159 male, 82 female,
      mean age 46.6 years, range 18-76) for whom six diagnostic clinicopathologic
      categories (including normality) were separately defined. The mean surface area
      of EMB, mean area of quantifiable adipose tissue, and percentage area
      attributable to fat were determined by computer-based morphometry to be 6.5
      mm(2), 0.4 mm(2), and 6.5%, respectively. The mean number of biopsy pieces,
      number of pieces with fat, and percentage of pieces with fat were 4.1, 1.1, and
      28.9%, respectively. Patients with arrhythmogenic right ventricular dysplasia had
      greater percentage area attributable to fat (19.8% vs. 8.9%; p < 0.0027) and
      greater number of pieces with adipose tissue (2.9 vs. 1.0, p < 0.0001) than did
      patients in diagnostic categories with the next most fatty EMB. There were no
      differences between males and females in EMB surface area fat or percentage of
      pieces with fat. Older patients (above the mean age) had greater adipose tissue
      in EMB (percentage area attributable to fat) than did younger patients (8.1% vs.
      4.8%; p < 0.01). Body mass index (kg/m(2)) did not correlate with percentage EMB
      tissue area attributable to fat. Larger EMBs (above the mean area) were neither
      more frequently nor more involved by fat than were smaller biopsy specimens (6.4%
      vs 6.6% fat, respectively). Typically, adipose tissue in EMB percolated widely
      through the myocardium, and the mean number of EMB pieces did not influence the
      likelihood of finding fat deposits. Fat was intimately associated with blood
      vessels and was frequently associated with small areas of interstitial and
      replacement fibrosis. The high frequency of adipose tissue in EMB and the
      relatively large area constituted by fat in some EMB supports autopsy
      observations that focal and widespread fatty infiltration of the right
      ventricular endomyocardium is to be expected and reflected in EMB sampling.
      Excessive myocardial fat may play a pathogenic role in cardiomyopathy. 

PMID- 25990771
TI  - Myocardial capillaries and autonomic nerves in diabetes: Morphometric study of
      auricles from bypass surgery biopsies.
AB  - Patients with diabetes mellitus are excessively vulnerable to myocardial ischemia
      and often suffer from autonomic cardiac dysfunction. They are also known to have
      specific capillary pathology and abnormalities of substances essential for the
      neoangiogenic cascade. These background data led us to the hypothesis that the
      severity of ischemic heart disease in diabetes is attributable (at least in part)
      to microcirculatory and autonomic inadequacy caused by microangiopathy and
      failure of postischemic adaptive neoangiogenesis. To test this hypothesis we
      compared myocardial capillaries, autonomic nerve endings of 19 diabetics, 30
      normoglycemics with ischemic heart disease, and 9 valve replacements serving as
      nonischemic controls. Right atrial appendages obtained during coronary bypass
      surgery were utilized for light, fluorescent, and electron microscopic
      morphometry. Although in this series there were no significant differences in the
      clinical and laboratory hemodynamic values between the ischemic normoglycemic and
      diabetic patients, the latter showed marked capillary and nerve terminal
      pathology, and their capillary density as well as capillary to myofiber ratios
      were significantly lower. In addition, the mean capillary area, volume fraction,
      and intercapillary distance were higher in diabetics. The mean area of the nerve
      varicosities was also smaller, and this was correlated with capillary density. We
      concluded that the findings support the hypothesis that cardiac vulnerability in
      diabetes is connected with inadequate adaptive neoangiogenesis and that this
      seems to be associated with atrophic changes in the nerve terminals. 

PMID- 25990772
TI  - New aspects concerning the morphology and significance of coronary muscle
      bridges.
AB  - Intramural courses of the coronary arteries in the sense of coronary muscle
      bridges are frequent autopsy findings, whereas only the more pronounced forms are
      accessible to clinicoangiographic detection. Functional significance is
      attributable to morphologic forms that show a pronounced intramural course and to
      those exhibiting quantitative cross-sectional changes. In addition to the known
      morphometric findings in the case of coronary muscle bridges, we found a stenosis
      like narrowing of intramurally coursing arteries without alterations of the
      intima. We observed such quantitative coronary artery findings in four cases with
      different causes of death, and in this paper we discuss the possible functional
      significance of this special type of coronary muscle bridge. 

PMID- 25990773
TI  - Persistently increased expression of the transforming growth factor-beta1 gene in
      human vascular restenosis: Analysis of 62 patients with one or more episode of
      restenosis.
AB  - Transforming growth factor-beta-1 (TGF-beta1) is a multifunctional cytokine with
      both growth-promoting and growth-inhibiting properties. Moreover, there is
      abundant evidence that TGF-beta1 is the principal growth factor responsible for
      regulating proteoglycan synthesis in human blood vessels. To determine the
      potential contribution of TGF-beta1 to restenosis, the current investigation
      sought to determine the time course of expression postangioplasty of the TGF
      beta1 gene. In situ hybridization was performed on tissue specimens obtained by
      directional atherectomy from 62 patients who had previously undergone angioplasty
      of native coronary or peripheral arteries and/or saphenous vein bypass grafts.
      The time interval between angioplasty and atherectomy was 1 hour to 25 months (M
      +/- SEM = 5 +/- 4 months) for all 62 patients, 5 +/- 4 months for coronary
      arterial specimens, 8 +/- 5 months for vein graft specimens, and 7 +/- 3 months
      for peripheral arterial specimens. TGF-beta1 mRNA expression remained
      persistently increased independent of the site from or time interval following
      which the specimen was obtained. For saphenous vein by pass grafts, TGF-beta1
      expression was highest in specimens retreived from patients with multiple versus
      single episodes of restenosis (16 +/- 5 vs. 6 +/- 5 grains/nucleus, p < 0.01).
      TGF-beta1 expression did not correlate with patient age, sex, or known risk
      factors for coronary heart disease. The persistently augmented expression of TGF
      beta1 observed in the present series of restenosis lesions provides further
      support for the concept that TGF-beta1 influences growth and development of
      restenosis plaque. 

PMID- 25990774
TI  - Plexogenic pulmonary hypertension in systemic lupus erythematosus: Report of two
      cases and review of the literature.
AB  - From the autopsy records of the Mayo Clinic, two patients with systemic lupus
      erythematosus were identified in whom plexogenic pulmonary hypertension also
      developed. Both were women (23 and 30 years old). Their pulmonary artery
      pressures were 96/30 and 115/45 mm Hg, respectively, and their survival after the
      diagnosis of pulmonary hypertension was only 21 and 19 months, respectively. To
      our knowledge, only two other cases have been reported. Thus, plexogenic
      pulmonary hypertension among patients with lupus is rare but is associated with a
      poor prognosis. 

PMID- 25990775
TI  - Laparoscopic hand-assisted adrenal sparing surgery for a giant adrenal
      myelolipoma: A case report.
AB  - INTRODUCTION: Adrenal myelolipoma is a rare, benign tumor. Surgical resection is
      advocated in case of symptomatic, large size (> 4cm), increase of size on follow
      up and atypical appearance on imaging. Laparoscopic adrenalectomy is currently
      the gold standard operation for managing benign adrenal mass. However, to date,
      laparoscopic entire resection of ipsilateral adrenal gland with the tumor have
      been mainly reported in the literature. Under clinical circumstances, adrenal
      sparing surgery underused as first-line therapy for adrenal tumors. CASE
      PRESENTATION: We present a case of adrenal myelolipoma involving the right
      adrenal gland of a 45-year-old woman who presented with right-sided flank pain.
      On radiologic and endocrine evaluation, she was diagnosed with a giant adrenal
      myelolipoma (> 8cm). Right hand-assisted laparoscopic partial adrenalectomy was
      performed, and postoperative recovery was uneventful. Finally, histological
      examination confirmed adrenal myelolipoma. On follow-up computed tomography,
      there was no residual tumor and the remaining right adrenal gland. CONCLUSION:
      Our report suggests that hand-assisted laparoscopic partial adrenalectomy could
      be considered for appropriate removal of adrenal myelolipoma, even in giant
      adrenal myelolipoma.

PMID- 25990776
TI  - Sclerosing epithelioid fibrosarcoma of the kidney: clinicopathologic and
      molecular study of a rare neoplasm at a novel location.
AB  - Sclerosing epithelioid fibrosarcoma (SEF) is a rare fibrosarcoma variant with
      specific histomorphology and consistent translocation (EWSR1-CREB3L1/2). To date,
      110 cases have been reported; only 15 originated within the abdomen. With only 2
      cases reported parallel to our study and one case briefly mentioned in a previous
      series, primary renal SEF is exceptionally rare but might be underrecognized. We
      herein describe 2 cases affecting a 23-year-old woman and a 43-year-old man.
      Tumor size was 22 and 4.2 cm, respectively. Patient 1 developed skeletal and
      multiple pulmonary metastases. She died of disease 82 months later, despite
      aggressive multimodality therapy. Patient 2 has no evidence of recurrence or
      metastasis (8 months after surgery). Histologic examination showed similar
      appearance with monotonous bland medium-sized epithelioid cells with rounded
      slightly vesicular nuclei and clear cytoplasm imparting a carcinoma-like
      appearance set within a highly sclerotic hyaline fibrous stroma. The tumor cells
      were arranged in nests, single cell cords, trabeculae, or solid sheets with
      frequent entrapment of renal tubules and glomeruli. Immunohistochemistry showed
      strong expression of vimentin, bcl2, CD99, and MUC4, whereas cytokeratin and
      other markers were negative. Fluorescence in situ hybridization showed a
      translocation involving the EWSR1 gene locus in case 2. Molecular analysis in
      case 1 was not successful due to poor signal quality. To our knowledge, this is
      the second report documenting primary renal SEF. Awareness of this entity would
      help avoid misinterpretation as clear cell carcinoma, sclerosing perivascular
      epithelioid cell tumor, Xp.11 translocation carcinoma, and other more frequent
      neoplasms at this site. 

PMID- 25990777
TI  - Spotting the Signs: a national toolkit to help identify young people at risk of
      child sexual exploitation.

PMID- 25990778
TI  - Delaying the widespread emergence of cephalosporin-resistant gonorrhoea: what is
      the best target?

PMID- 25990779
TI  - Results of a pilot screening programme for genital and extragenital gonococcal
      and chlamydial infections in a military population following the repeal of 'Don't
      Ask, Don't Tell'.

PMID- 25990780
TI  - Treatment regimens in non-gonococcal urethritis.

PMID- 25990781
TI  - Researching stigmatised communities: lessons from a study of MSM in India.

PMID- 25990782
TI  - Anogenital preinvasive and invasive lesions in the Limpopo Province of South
      Africa.

PMID- 25990783
TI  - Survey of the laboratory diagnosis of gonorrhoea and chlamydial infection in the
      UK.

PMID- 25990784
TI  - Expression of umami-taste-related genes in the tongue: a pilot study for genetic
      taste diagnosis.
AB  - OBJECTIVE: Expression of taste-related genes in the tongue was analysed to
      develop a technique for genetic diagnosis of umami taste disorders. MATERIALS AND
      METHODS: Tissue samples were collected from healthy volunteers by scraping the
      foliate papillae of the tongue. Immunocytochemistry staining of gustducin, a
      taste-cell-specific G protein, and gene expression analysis by real-time
      polymerase chain reaction of beta-actin, gustducin (GNAT3) and umami receptors
      (T1R1, T1R3 and mGluR1) were performed. Changes in umami receptor expression
      following application of umami substances onto the tongue were analysed. RESULTS:
      Gustducin-positive cells were observed in the samples, indicating the presence of
      taste cells. Gene expression of beta-actin, GNAT3, T1R1 and T1R3 was detected in
      all seven samples tested, while that of mGluR1 was detected in four samples.
      Sequence analysis by NCBI Blast showed that each polymerase chain reaction
      product had a 99% rate of identification of its target sequence. Stimulation of
      the tongue with monosodium glutamate significantly upregulated the gene
      expression levels of T1R1 and T1R3, indicating that this method can detect
      alterations in umami-related gene expression. CONCLUSION: Evaluation of the
      expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be
      clinically useful for objective genetic diagnosis of umami taste disorders.

PMID- 25990785
TI  - Aldehyde inhibition of antioxidant enzymes in the blood of diabetic patients.
AB  - BACKGROUND: The aim of the present study was to examine the effect of aldehyde
      modification on antioxidant enzyme activity in diabetic patients. METHODS: The
      activity of commercially available antioxidant enzymes (catalase, glutathione
      peroxidase [GPx], and Cu,Zn-superoxide dismutase [SOD]) was determined in vitro
      prior to and after aldehyde modification. The activity of erythrocyte Cu,Zn-SOD
      was assayed in blood drawn from healthy donors, diabetic patients with
      decompensated carbohydrate metabolism, and diabetic patients after glucose
      lowering therapy. RESULTS: In vitro aldehyde modification had no effect on
      catalase activity, but diminished GPx and Cu,Zn-SOD activity. In diabetic
      patients with decompensated carbohydrate metabolism, glucose-lowering therapy
      significantly increased Cu,Zn-SOD activity, the effect being especially
      pronounced after administration of metformin. CONCLUSIONS: It is likely that
      metformin antagonizes the aldehyde-induced inhibition of erythrocyte Cu,Zn-SOD in
      diabetic patients more effectively than sulfonylurea drugs.

PMID- 25990787
TI  - Photoinduced electron transfer in a supramolecular triad produced by porphyrin
      anion-induced electron transfer from tetrathiafulvalene calix[4]pyrrole to
      Li(+)@C60.
AB  - Binding of a porphyrin carboxylate anion () to tetrathiafulvalene calix[4]pyrrole
      (TTF-C4P) results in electron transfer from TTF-C4P to Li(+)@C60 to produce the
      charge-separated state (1/TTF-C4P(+)/Li(+)@C60(-)) in benzonitrile. Upon
      photoexcitation of , photoinduced electron transfer from the triplet excited
      state of to TTF-C4P(+) occurs to produce the higher energy charge-separated state
      ((+)/TTF-C4P/Li(+)@C60(-)), which decays to the ground state with a lifetime of
      4.8 MUs. 

PMID- 25990786
TI  - Disclosing the Hidden Structure and Underlying Mutational Mechanism of a Novel
      Type of Duplication CNV Responsible for Hereditary Multiple Osteochondromas.
AB  - The additional mutational complexity associated with copy number variation (CNV)
      can provide important clues as to the underlying mechanisms of CNV formation.
      Correct annotation of the additional mutational complexity is, however, a
      prerequisite for establishing the mutational mechanism. We illustrate this point
      through the characterization of a novel ~230 kb EXT1 duplication CNV causing
      autosomal dominant hereditary multiple osteochondromas. Whole-genome sequencing
      initially identified the CNV as having a 22-bp insertion at the breakpoint
      junction and, unprecedentedly, multiple breakpoint-flanking micromutations on
      both sides of the duplication. Further investigation revealed that this genomic
      rearrangement had a duplication-inverted triplication-duplication structure, the
      inverted triplication being a 41-bp sequence synthesized from a nearby template.
      This permitted the identification of the sequence determinants of both the
      initiation (an inverted Alu repeat) and termination (a triplex-forming sequence)
      of break-induced replication and suggested a possible model for the repair of
      replication-associated double-strand breaks. 

PMID- 25990788
TI  - Energy Aspects of Thermal Molecular Switching: Molecular Thermal Hysteresis of
      Helicene Oligomers.
AB  - Molecular switching is a phenomenon by which a molecule reversibly changes its
      structure and state in response to external stimuli or energy. Herein, molecular
      switching is discussed from thermodynamic and kinetic aspects in terms of energy
      supply with an emphasis on the thermal switching exhibited by helicene oligomers.
      It includes the inversion of relative thermodynamic stability induced by
      temperature changes and molecular thermal hysteresis in a closed system. The
      thermal phenomenon associated with the oligomers involves
      population/concentration changes between metastable states under nonequilibrium
      thermodynamic control. 

PMID- 25990789
TI  - Reply to Jargin's comments: solid cancer increase among Chernobyl liquidators
      alternative explanation.

PMID- 25990791
TI  - Impact of malnutrition on postoperative delirium development after on pump
      coronary artery bypass grafting.
AB  - BACKGROUND & AIMS: Even though malnutrition is frequently observed in cardiac
      population outcome data after cardiac surgery in malnourished patients is very
      rare. No thorough research was done concerning the impact of malnutrition on
      neuropsychological outcomes after cardiac surgery. The aim of our study was to
      analyze the incidence of postoperative delirium development in malnourished
      patients undergoing on pump bypass grafting. METHODS: We performed a cohort study
      of adults admitted to Vilnius University Hospital Santariskiu Clinics for
      elective coronary artery bypass grafting. The nutritional status of the patients
      was assessed by Nutritional Risk Screening 2002 (NRS-2002) questionnaire the day
      before surgery. Patients were considered as having no risk of malnutrition when
      NRS-2002 score was less than 3 and at risk of malnutrition when NRS-2002 score
      was >=3. During ICU stay patients were screened for postoperative delirium
      development using the CAM-ICU method. and divided into two groups: delirium and
      non delirium. The statistical analysis was preformed to evaluate the differences
      between the two independent groups. The logistic regression model was used to
      evaluate the potential preoperative and intraoperative risk factors of
      postoperative delirium. RESULTS: Ninety-nine patients were enrolled in the study.
      Preoperative risk of malnutrition was detected in 24 % (n = 24) of the patients.
      The incidence of early postoperative delirium in overall study population was 8.0
      % (n = 8). The incidence of the patients at risk of malnutrition was
      significantly higher in the delirium group (5 (62.5 %) vs 19 (20.9 %), p
      <0.0191). In multivariate logistic regression analysis risk of malnutrition
      defined by NRS 2002 was an independent preoperative and intraoperative risk
      factor of postoperative delirium after coronary artery bypass grafting (OR:
      6.316, 95 % CI: 1.384-28.819 p = 0.0173). CONCLUSIONS: Preoperative malnutrition
      is common in patients undergoing elective coronary artery bypass grafting.
      Nutrition deprivation is associated with early postoperative delirium after on
      pump coronary artery bypass grafting.

PMID- 25990792
TI  - Outcome of preoperative weight loss in colorectal surgery.
AB  - BACKGROUND: There are limited data regarding the outcomes of patients with
      preoperative weight loss. We sought to identify complications associated with
      preoperative weight loss in colorectal surgery. METHODS: The National Surgical
      Quality Improvement Program database was used to examine the clinical data of
      patients undergoing colorectal resection from 2005 to 2012 who had unintentional
      preoperative weight loss (more than 10% in 6 months of surgery). Multivariate
      analysis was performed to quantify the association of weight loss with
      postoperative complications. RESULTS: We sampled a total of 79,696 patients who
      were admitted nonemergently for colorectal resection. The rate of preoperative
      unintentional weight loss was 3%. There were associations between preoperative
      weight loss with preoperative hypoalbuminemia (serum albumin level < 3.5 g/dL)
      (adjusted odds ratio [AOR] 2.58, P < .01). Postoperative mortality (AOR 1.74, P <
      .01) and complications of myocardial infarction (AOR 1.97, P = .03) and
      ventilator dependency (AOR 1.54, P = .03) had strong associations with weight
      loss. CONCLUSIONS: A history of unintentional weight loss can be used to predict
      mortality and morbidity rates and as a marker for nutritional assessment in
      colorectal surgery. Cardiopulmonary complications have significant association
      with preoperative weight loss.

PMID- 25990790
TI  - Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are
      necessary for cytoprotection against cell damage.
AB  - It is well known that haem serves as the prosthetic group of various
      haemoproteins that function in oxygen transport, respiratory chain, and drug
      metabolism. However, much less is known about the functions of the catabolites of
      haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide
      (CO), and biliverdin, which is then converted to bilirubin. Owing to difficulties
      in measuring bilirubin, however, the generation and transport of this end product
      remain unclear despite its clinical importance. Here, we used UnaG, the recently
      identified bilirubin-binding fluorescent protein, to analyse bilirubin production
      in a variety of human cell lines. We detected a significant amount of bilirubin
      with many non-blood cell types, which was sensitive to inhibitors of haem
      metabolism. These results suggest that there is a basal level of haem synthesis
      and its conversion into bilirubin. Remarkably, substantial changes were observed
      in the bilirubin generation when cells were exposed to stress insults. Since the
      stress-induced cell damage was exacerbated by the pharmacological blockade of
      haem metabolism but was ameliorated by the addition of biliverdin and bilirubin,
      it is likely that the de novo synthesis of haem and subsequent conversion to
      bilirubin play indispensable cytoprotective roles against cell damage. 

PMID- 25990793
TI  - Subungual fibro-osseous pseudotumour of the toe.
AB  - Subungual fibro-osseous pseudotumour of the toe is a rare osseous soft tissue
      tumour of which only six cases have been described in the literature. We present
      a case in a teenage boy that posed an instructive diagnostic challenge and
      discuss the distinguishing features of the various differential diagnoses. The
      subungual location is very rare. For such tumours, radiology is as vital as
      histopathology in making a diagnosis and excluding neoplasia. Accurate diagnosis
      requires careful clinico-pathological and radiological correlation. These sorts
      of lesions may present to the dermatologist, not always the foot surgeon. 

PMID- 25990794
TI  - Fibromyalgia with chronic rheumatic diseases in South Korea: a comparison of
      clinical and American College of Rheumatology criteria.
AB  - AIM: To describe the prevalence and characteristics of fibromyalgia (FM) in
      patients with underlying rheumatic disease, and to compare it by three different
      measures. METHODS: We studied 546 patients with chronic rheumatic diseases who
      attended our rheumatology clinic. If patients answered all of a screening
      questionnaire with yes, then we considered patients to be having widespread pain
      as assessed by the fibromyalgia impact questionnaire (FIQ), widespread pain index
      (WPI), and symptom severity (SS). A physician administered the tender point (TP)
      exam and clinician's judgment of FM. We collected demographics, clinical and
      laboratory features. RESULTS: One hundred and sixty-four (30.0%) patients among
      546 cases had a further exam. The male-to-female count was 25 : 139. The mean age
      was 49.7 years, disease duration 3.7 years, TP counts 4.2, FIQ score 47.0 and WPI
      with SS score was 11.1. We classified 17 patients (10.4%) with concomitant FM
      with widespread pain by tender point exam, 56 patients (34.2%) by WPI with SS,
      and 36 patients (22.0%) by a clinician's judgment. A total of 70.6% (n = 12) of
      those classified as FM by 1990 American College of Rheumatology (ACR) criteria
      wee categorized as FM by clinician's judgment, while 33.3% by clinician's
      judgment were classified by 1990 ACR criteria. CONCLUSIONS: We found a 10.4~34.2%
      prevalence of concomitant FM in the patients with chronic widespread pain. The
      1990 ACR criteria were the most restrictive except for SLE. Although The 2010 ACR
      criteria had a wide spectrum, it can be used for FM diagnosis even in the patient
      with underlying rheumatic diseases.

PMID- 25990795
TI  - High numbers of CD68+ tumor-associated macrophages correlate with poor prognosis
      in extranodal NK/T-cell lymphoma, nasal type.
AB  - Many studies have demonstrated that tumor-associated macrophages (TAMs) were a
      prognostic indicator in patients with B cell lymphoma. But, we know little about
      the clinical significance of TAMs in extranodal natural killer/T cell
      lymphoma(ENKTL), nasal type. CD68 expression was detected using
      immunohistochemistry to determine the numbers of TAMs in 70 ENKTL patients, and
      the data were used to evaluate its relationship with clinicopathological
      features, treatment response, and prognosis. Patients with high number of
      infiltrated CD68+ TAMs (>60/hpf) at diagnosis tended to have more adverse
      clinical characteristics. Patients with low CD68+ TAM content (<60/hpf) at
      diagnosis had better overall survival (P = 0.003) and progression-free survival
      (P = 0.002) and achieved higher complete remission rates (P = 0.008).
      Multivariate analysis revealed that CD68 + TAM content, Ki-67 index, and stage
      III and IV were independent prognostic factors for both OS and PFS. Using the
      International Prognostic Index or Korean Prognostic Index for extranodal NK/T
      cell lymphoma, nasal type, the majority of patients were in the low-risk
      category. CD68 + TAM content was helpful to differentiate the low-risk patients
      with different survival outcomes. Our data suggest that CD68+ TAM content at
      diagnosis is a powerful predictor of prognosis for ENKTL, which suggests a role
      for TAMs in the pathogenesis of this disease and offers new insight into
      potential therapeutic strategies. 

PMID- 25990796
TI  - Wound healing effects of dipeptidyl peptidase-4 inhibitors: An emerging concept
      in management of diabetic foot ulcer-A review.
AB  - OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors have a well-known effect on
      glycaemic control in patients with diabetes but little is known on their wound
      healing role in this group of population. This paper reviews the effects of DPP-4
      inhibitors on wound healing of diabetic foot ulcers. METHODS: Published data on
      effects and mechanism of DDP-4 inhibitors on wound healing were derived from
      Medline, PubMed and Google Scholar search of English language literature from
      1994 to 2014 using the key words such as "DPP-4 inhibitors", "endothelial
      healing" "diabetes" and "chronic ulcers". RESULTS: DPP-4 inhibitors show a
      potential benefit in processes of wound healing in diabetic chronic foot ulcers.
      The enzyme inhibitors promote recruitment of endothelial progenitor cells and
      allow the final scaffolding of wounds. Furthermore DPP-4 inhibitors augment
      angiogenesis and have widespread effects on optimising the immune response to
      persistent hypoxia in chronic diabetes wounds. CONCLUSION: DPP-4 inhibitors show
      promise in the local wound healing of diabetic foot ulcers in addition to its
      already established glycaemic control. In the light of high rate of amputations
      due to non-healing ulcers with profound psychological and economical liability,
      more investigations on the usefulness of DPP-4 inhibitors in the high risk
      diabetes population are needed.

PMID- 25990797
TI  - Lives matter. Do votes? Invited commentary on "Black lives matter: Differential
      mortality and the racial composition of the U.S. electorate, 1970-2004".
AB  - Racial health disparities in the United States are produced and perpetuated
      through public policies that differentially allocate risks and resources for
      health. Elected officials have the ability modify the structural determinants of
      racial health disparities through policy decisions and, through voting, the
      electorate can influence the extent to which these policy decisions promote
      health equity. In this commentary, I synthesize research on the voting behavior
      of electorates and policy decisions and present strategies to foster
      sociopolitical environments that are conducive to the implementation and
      enforcement of racial health disparity reduction initiatives. There is a need for
      research that contributes to a more comprehensive understanding of the role of
      voting in health policy making processes and further development of empirically
      based policy advocacy strategies. 

PMID- 25990798
TI  - Transfer of genetic therapy across human populations: molecular targets for
      increasing patient coverage in repeat expansion diseases.
AB  - Allele-specific gene therapy aims to silence expression of mutant alleles through
      targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP
      linkage to disease varies between populations, making such molecular therapies
      applicable only to a subset of patients. Moreover, not all SNPs have the
      molecular features necessary for potent gene silencing. Here we provide knowledge
      to allow the maximisation of patient coverage by building a comprehensive
      understanding of SNPs ranked according to their predicted suitability toward
      allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral
      sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy,
      myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several
      spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows
      that most annotated SNPs are not suitable for potent allele-specific silencing
      across populations because of suboptimal sequence features and low variability
      (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high
      heterozygosity across populations, and preferentially targeting SNPs that lead to
      purine:purine mismatches in wild-type alleles to obtain potent allele-specific
      silencing. We therefore provide fundamental knowledge on strategies for
      optimising patient coverage of therapeutics for microsatellite expansion
      disorders by linking analysis of population genetic variation to the selection of
      molecular targets. 

PMID- 25990799
TI  - Clinical utility gene card for: Proximal spinal muscular atrophy (SMA) - update
      2015.

PMID- 25990800
TI  - S100B and ADMA in cerebral small vessel disease and cognitive dysfunction.
AB  - BACKGROUND: Glial cell activation and endothelial dysfunction are thought to
      contribute to the pathophysiology of cerebral small vessel disease (SVD). The
      purpose of the present study was to determine if levels of S100B, a protein
      highly expressed in glial cells, and asymmetric dimethylarginine (ADMA), which
      promotes endothelial dysfunction, are elevated in the serum of patients with SVD
      and correlate with their cognitive functioning. METHODS: The serum levels of
      S100B and ADMA were measured with enzyme-linked immunosorbent assays in 210
      patients with SVD and 207 controls. Cognitive functioning was evaluated using the
      Montreal Cognitive Assessment. SVD lesions were categorized as isolated lacunar
      infarcts (ILI), multiple lacunar infarcts, leukoaraiosis (LA), and LA with
      cerebral atrophy using magnetic resonance imaging. RESULTS: SVD patients were
      significantly older, and more likely to have hypertension, diabetes, and heart
      disease, and smoke compared to controls (Ps<0.05). Plasma levels of S100B and
      ADMA were significantly higher in SVD patients (Ps<0.05), though only S100B was
      significant after adjusting for the confounding factors. Subtype analyses
      indicated that ADMA levels were differentially altered depending on lesion type,
      particularly in cases with ILI and LA (Ps<0.05). Compared with controls, SVD
      patients had significant cognitive impairment that was most profound in the cases
      with LA (all Ps<0.05). Levels of S100B and ADMA were significantly correlated
      with cognitive decline in patients with LA (P<0.05). CONCLUSION: S100B and ADMA
      are elevated in SVD, and are associated with cognitive impairment in patients
      with LA lesions.

PMID- 25990801
TI  - Blurred boundaries between organic and functional etiology: A man with a jerky
      leg.

PMID- 25990802
TI  - Psychotic experiences and PTSD: exploring associations in a population survey.
AB  - BACKGROUND: Extensive evidence has shown that experiencing a traumatic event and
      post-traumatic stress disorder (PTSD) are associated with experiences of
      psychosis. However, less is known about specific PTSD symptoms and their
      relationship with psychotic experiences. This study aimed to examine the
      relationship between symptoms of PTSD with paranoia and auditory hallucinations
      in a large-scale sample. METHOD: The Adult Psychiatric Morbidity Survey (APMS)
      was utilized to examine the prevalence of lifetime trauma, symptoms of PTSD, and
      experiences of paranoia and auditory hallucinations (n = 7403). RESULTS: There
      were significant bivariate associations between symptoms of PTSD and psychotic
      experiences. Multiple logistic regression analyses indicated that reliving and
      arousal symptoms were significant predictors for paranoia while reliving, but not
      arousal symptoms, also significantly predicted auditory hallucinations. A dose
      response relationship was found, the greater the number of PTSD symptoms, the
      greater the odds were of experiencing both paranoia and hallucinations.
      CONCLUSIONS: These findings illustrate that symptoms of PTSD are associated with
      increased odds of experiencing auditory hallucinations and paranoia. Overlaps
      appear to be present between the symptoms of PTSD and psychotic experiences.
      Increasing awareness of this association may advance work in clinical practice.

PMID- 25990803
TI  - Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus and
      varicella zoster virus diseases after autologous hematopoietic stem cell
      transplantation.
AB  - Limited data are available on prophylaxis for herpes simplex virus (HSV) and
      varicella zoster virus (VZV) disease following autologous hematopoietic stem cell
      transplantation (auto-HCT). We retrospectively reviewed the clinical charts of
      105 consecutive patients who underwent their first auto-HCT at our institution
      between September 2007 and June 2014. Before August 2009, 30 patients received
      oral acyclovir at 1000 mg/day until engraftment, whereas after September 2009, 69
      patients received oral acyclovir at 200 mg/day. After engraftment, acyclovir was
      continued at 200 mg/day at the discretion of the attending physicians in both
      groups. The cumulative incidence of HSV disease at 1 year after auto-HCT was 7.7
      and 4.5 % in patients who received oral acyclovir at 1000 and 200 mg/day,
      respectively (P = 0.75). Patients were next divided into three groups according
      to the timing at which acyclovir prophylaxis was stopped after auto-HCT; at
      engraftment, between engraftment and 1 year after auto-HCT, and later than 1
      year. The cumulative incidence of VZV disease was 25.8, 7.7, and 0.0 % at 1 year,
      respectively. This study suggests that low-dose acyclovir prophylaxis may be
      effective for preventing HSV and VZV disease after auto-HCT. Our findings support
      the recommendation of acyclovir prophylaxis within the first year after auto-HCT.

PMID- 25990804
TI  - The planar cell polarity protein Vangl2 is required for retinal axon guidance.
AB  - Vangl2 plays a critical role in the establishment of planar cell polarity (PCP).
      Previously, we detected expression of Vangl2 in the developing retina during late
      embryogenesis, which led us to investigate the possible role of Vangl2-mediated
      PCP signaling in eye development. We have generated a Vangl2(BGeo) knock-in mouse
      allowing us to evaluate Vangl2 mRNA expression during retinal development, and
      used an isoform-specific antibody to examine Vangl2 protein expression in
      cryosections. To investigate the role of Vangl2 in retinal development, we
      examined eyes taken from embryos homozygous for independent alleles of Looptail
      (Lp, Lp(m1jus) ) mutant mice. We found that Vangl2 mRNA and protein are
      dynamically expressed in the developing embryonic and postnatal retina, with
      Vangl2 expression becoming progressively restricted to the ganglion cell layer
      and optic nerve as the retina matures. The expression pattern of Vangl2
      transcript and protein is most prominent in retinal ganglion cells (RGC), and
      their axons. Additionally, we show that Vangl2 is required for retinal and optic
      nerve development as Vangl2 (Lp/Lp) mutant embryos display a significantly
      reduced eye size, marked thickening of the retina, and striking abnormalities in
      the morphology of the optic nerve (significant hypoplasia, and aberrant exit
      trajectory). Notably, we identified a salient intraretinal axon guidance defect
      in Vangl2 (Lp/Lp) mutant embryos through which axon bundles traverse the entire
      thickness of the retina and become trapped within the subretinal space. Our
      observations identify a new and essential role for Vangl2-dependent PCP signaling
      in the intraretinal path-finding of RGC axons.

PMID- 25990805
TI  - Clinical utility of femtosecond laser-assisted astigmatic keratotomy after
      cataract surgery.
AB  - PURPOSE: To examine the clinical utility of femtosecond laser-assisted astigmatic
      keratotomy (FSL-AK) for eyes after cataract surgery. METHODS: Eight eyes of 6
      patients with an intraocular lens and corneal astigmatism of 2.0 diopters (D) or
      more underwent FSL-AK. The mean preoperative manifest cylindrical refraction was
      2.88 +/- 0.64 D and the mean corneal astigmatism was 2.84 +/- 0.83 D. Paired
      symmetrical arcuate incisions were created with the same settings, except for the
      incision depth. Uncorrected distance visual acuity (UDVA), manifest cylindrical
      power, and surgically induced astigmatism (SIA) were measured at 1 day, 1 week,
      and 1 month postoperatively. Fourier analysis of corneal topography and incision
      depths measured with anterior-segment optical coherence tomography were evaluated
      1 month postoperatively. RESULTS: In all eyes, the UDVA improved at 1 week and 1
      month postoperatively, and the manifest cylinder also decreased postoperatively,
      while the SIA showed overcorrections in 6 eyes. Fourier analysis showed decreases
      in spherical and regular astigmatic components and increases in higher-order
      irregularity. The mean incision depth was measured as 60 um deeper than the
      intended depth. CONCLUSION: The FSL-AK effectively reduced corneal astigmatism
      and improved the UDVA, although it was demonstrated that the deeper incisions led
      to overcorrection.

PMID- 25990806
TI  - Residence in Skilled Nursing Facilities Is Associated with Tigecycline
      Nonsusceptibility in Carbapenem-Resistant Klebsiella pneumoniae.
AB  - OBJECTIVE: To determine the rates of and risk factors for tigecycline
      nonsusceptibility among carbapenem-resistant Klebsiella pneumoniae (CRKPs)
      isolated from hospitalized patients. DESIGN: Multicenter prospective
      observational study. SETTING: Acute care hospitals participating in the
      Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRaCKle).
      PATIENTS: A cohort of 287 patients who had CRKPs isolated from clinical cultures
      during hospitalization. METHODS: For the period from December 24, 2011 to October
      1, 2013, the first hospitalization of each patient with a CRKP during which
      tigecycline susceptibility for the CRKP isolate was determined was included.
      Clinical data were entered into a centralized database, including data regarding
      pre-hospital origin. Breakpoints established by the European Committee on
      Antimicrobial Susceptibility Testing (EUCAST) were used to interpret tigecycline
      susceptibility testing. RESULTS: Of 287 patients included in the final cohort,
      155 (54%) had tigecycline-susceptible CRKPs. Of all index isolates, 81 (28%) were
      tigecycline-intermediate and 51 (18%) were tigecycline resistant. In multivariate
      modeling, independent risk factors for tigecycline nonsusceptibility were (1)
      admission from a skilled nursing facility (OR, 2.51; 95% CI, 1.51-4.21; P=.0004),
      (2) positive culture within 2 days of admission (OR, 1.82; 95% CI, 1.06-3.15;
      P=.03), and (3) receipt of tigecycline within 14 days (OR, 4.38, 95% CI, 1.37
      17.01, P=.02). CONCLUSIONS: In hospitalized patients with CRKPs, tigecycline
      nonsusceptibility was more frequently observed in those admitted from skilled
      nursing facilities and occurred earlier during hospitalization. Skilled nursing
      facilities are an important target for interventions to decrease antibacterial
      resistance to antibiotics of last resort for treatment of CRKPs.

PMID- 25990807
TI  - Weight and season affects androstenone and skatole occurrence in entire male pigs
      in organic pig production.
AB  - To investigate the extent to which the level of androstenone and skatole
      decreases with a decrease in live weight and/or age at slaughter of entire male
      pigs produced under organic standards, 1174 entire male pigs were raised in
      parallel in five organic herds, distributed across four batches in summer and
      winter. The median androstenone level was high for organic entire male pigs (1.9
      ug/g), but varied greatly both within and between herds. Median skatole level was
      0.05 ug/g, also with a wide range both within and between herds. Decreasing live
      weight over the range of 110 +/- 15.6 kg s.d. was found to decrease androstenone
      as well as skatole concentration, however, with different patterns of
      association. Age did not have significant direct effect on either androstenone or
      skatole levels. Androstenone levels were higher during winter than summer
      (P<0.0001), but no difference in skatole was found between seasons. The study
      concludes that decreasing live weight at slaughter could be an applicable
      management tool to reduce risk of boar taint and the level of tainted carcasses
      for a future production of entire male pigs within the organic pig production
      system, although further studies are needed as great variation in boar taint was
      found also for low weight animals.

PMID- 25990809
TI  - [Typical problems in pediatric emergencies: Possible solutions].
AB  - BACKGROUND: Pediatric emergencies are rare and challenging for health care
      providers, parents, and patients. The purpose of this article is to highlight
      typical difficulties in the treatment of pediatric patients and to discuss
      potential solutions. MATERIALS AND METHODS: This article is based on a selective
      literature search using PubMed and the experience of the authors in the field of
      simulation and pediatric emergencies. RESULTS: Inexperience with pediatric
      emergencies, uncertainty in technical skills, in the usage of pediatric equipment
      and in medication dosage as well as parental presence foster the perception of
      stress and potentially compromise the success of patient care. Beside
      implementation of simplified technical skill devices (e.g., intraosseous vascular
      access system, supraglottic airway devices, and alternative approaches for drug
      administration), there have been many efforts in recent years to improve patient
      safety. Tools for estimating body weight and precalculated drug-dosing charts
      have been implemented as well as standardized courses for guidelines, technical
      skills, and team-related skills have been established. CONCLUSION: To improve
      patient safety, regular training and implementation of a sustainable safety
      culture are mandatory.

PMID- 25990808
TI  - Cell mediated immunity against HPV16 E2, E6 and E7 peptides in women with
      incident CIN and in constantly HPV-negative women followed-up for 10-years.
AB  - BACKGROUND: Virus-specific cell-mediated immunity (CMI) plays a role in the
      outcome of genital HPV infections. To cast further light on the question why most
      women clear their HPV infection while others develop high-grade cervical
      intraepithelial neoplasia (CIN), we analyzed HPV16 E2-, E6- and E7 -specific CMI
      in women who developed CIN during a 10-year follow-up of the Finnish Family HPV
      cohort. METHODS: Overlapping 30-35 mer peptides covering the entire HPV16 E2-, E6
      and E7 protein sequences were used for defining the lymphocyte proliferation
      capacity, cytokine production (IL-2, IL-5, IL-10, IL-17A, IFN-gamma and TNF
      alpha) and numbers of HPV16 -specific CD4+ CD25+ Foxp3+ regulatory T-cells in 10
      women who developed CIN, and in 22 control women who tested constantly HPV
      negative during the follow-up. HPV-specific CMI was related to the demographic
      data including sexual behavior, smoking and alcohol consumption. RESULTS: Women
      with CIN and their controls had similar T-cell mediated immunity against HPV16
      E2, E6 and E7 peptide pools. However, nearly fourfold higher T-cell reactivity
      against common antigens was found in the CIN women than in the healthy donors (p
      = 0.001). HPV16 E6 stimulation resulted in higher IL-17A secretion in the
      controls than in the CIN women (p = 0.035). Smoking and use of alcohol affected
      the T-cell response to common antigens but not to HPV peptides (p = 0.032 and
      0.045, respectively). CONCLUSION: While both the CIN women and controls exhibited
      an HPV16-specific CMI, IL-17A might be of importance in HPV induced pathology.
      The hyper-responsiveness of the CIN patients to common antigens needs further
      studies. Smoking and alcohol had no effect on HPV-specific CMI.

PMID- 25990810
TI  - [Pediatric emergencies--a major challenge].

PMID- 25990811
TI  - A self-assembling fluorescent dipeptide conjugate for cell labelling.
AB  - Derivatives of fluorophore FITC (fluorescein isothiocyanate) are widely used in
      bioassays to label proteins and cells. An N-terminal leucine dipeptide is
      attached to FITC, and we show that this simple conjugate molecule is
      cytocompatible and is uptaken by cells (human dermal and corneal fibroblasts) in
      contrast to FITC itself. Co-localisation shows that FITC-LL segregates in peri
      nuclear and intracellular vesicle regions. Above a critical aggregation
      concentration, the conjugate is shown to self-assemble into beta-sheet
      nanostructures comprising molecular bilayers. 

PMID- 25990812
TI  - Differential effect of intrauterine growth restriction on childhood
      neurodevelopment: a systematic review.
AB  - BACKGROUND: Neurodevelopmental disorders are increasingly believed to originate
      from intrauterine growth restriction (IUGR). Current reviews exploring the
      neurodevelopmental effects of IUGR, however, are mostly based on birthweight, an
      inadequate proxy. OBJECTIVE: We aimed to examine the association between IUGR
      documented in utero, and neurodevelopmental outcomes during childhood. SEARCH
      STRATEGY: Medline, CINAHL, PsycInfo and Scopus were searched for relevant studies
      published after 1970. SELECTION CRITERIA: The analysis included studies that
      identified IUGR in utero, with follow-up assessments between 1 month and 12 years
      of age. DATA COLLECTION AND ANALYSIS: Data was extracted for cognitive,
      behavioural, language, motor, hearing, vision or sleep outcomes. Studies were
      summarised separately for children born at <35 and >=35 weeks gestation. MAIN
      RESULTS: Of 28 876 titles identified, 38 were suitable for inclusion. IUGR
      children born >=35 weeks gestation scored on average 0.5 SD lower than non-IUGR
      children across all neurodevelopmental assessments. IUGR children born <35 weeks
      of gestation scored approximately 0.7 SD lower than non-IUGR children across all
      neurodevelopmental assessments. IUGR children with evidence of fetal circulatory
      redistribution (preferential perfusion of the brain) had more severe
      neurodevelopmental impairments than those born IUGR alone. CONCLUSIONS: IUGR
      increases the risk of neurodevelopmental impairment during childhood
      differentially across domains. IUGR children born preterm or with evidence of
      fetal circulatory redistribution are more severely affected. TWEETABLE ABSTRACT:
      IUGR is associated with an overall risk for neurodevelopmental delay in a range
      of neurodevelopmental domains.

PMID- 25990813
TI  - Characterization of Nanoporous Materials with Atom Probe Tomography.
AB  - A method to characterize open-cell nanoporous materials with atom probe
      tomography (APT) has been developed. For this, open-cell nanoporous gold with
      pore diameters of around 50 nm was used as a model system, and filled by electron
      beam-induced deposition (EBID) to obtain a compact material. Two different EBID
      precursors were successfully tested-dicobalt octacarbonyl [Co2(CO)8] and diiron
      nonacarbonyl [Fe2(CO)9]. Penetration and filling depth are sufficient for focused
      ion beam-based APT sample preparation. With this approach, stable APT analysis of
      the nanoporous material can be performed. Reconstruction reveals the composition
      of the deposited precursor and the nanoporous material, as well as chemical
      information of the interfaces between them. Thus, it is shown that, using an
      appropriate EBID process, local chemical information in three dimensions with sub
      nanometer resolution can be obtained from nanoporous materials using APT. 

PMID- 25990814
TI  - HIV reservoirs as obstacles and opportunities for an HIV cure.
AB  - The persistence of HIV reservoirs remains a formidable obstacle to achieving
      sustained virologic remission in HIV-infected individuals after antiretroviral
      therapy (ART) is discontinued, even if plasma viremia has been successfully
      suppressed for prolonged periods of time. Numerous approaches aimed at
      eradicating the virus, as well as maintaining its prolonged suppression in the
      absence of ART, have had little success. A better understanding of the
      pathophysiologic nature of HIV reservoirs and the impact of various interventions
      on their persistence is essential for the development of successful therapeutic
      strategies against HIV or the long-term control of infection. Here, we discuss
      the persistent HIV reservoir as a barrier to cure as well as the current
      therapeutic strategies aimed at eliminating or controlling the virus in the
      absence of ART. 

PMID- 25990815
TI  - Antioxidant Treatments Recover the Alteration of Auditory-Evoked Potentials and
      Reduce Morphological Damage in the Inferior Colliculus after Perinatal Asphyxia
      in Rat.
AB  - Maturation of the auditory pathway is dependent on the central nervous system
      myelination and it can be affected by pathologies such as neonatal hypoxic
      ischemic (HI) encephalopathy. Our aim was to evaluate the functional integrity of
      the auditory pathway and to visualize, by histological and cellular methods, the
      damage to the brainstem using a neonatal rat model of HI brain injury. To carry
      out this morphofunctional evaluation, we studied the effects of the
      administration of the antioxidants nicotine, melatonin, resveratrol and
      docosahexaenoic acid after hypoxia-ischemia on the inferior colliculus and the
      auditory pathway. We found that the integrity of the auditory pathway in the
      brainstem was altered as a consequence of the HI insult. Thus, the auditory
      brainstem response (ABR) showed increased I-V and III-V wave latencies. At a
      histological level, HI altered the morphology of the inferior colliculus neurons,
      astrocytes and oligodendricytes, and at a molecular level, the mitochondria
      membrane potential and integrity was altered during the first hours after the HI
      and reactive oxygen species (ROS) activity is increased 12 h after the injury in
      the brainstem. Following antioxidant treatment, ABR interpeak latency intervals
      were restored and the body and brain weight was recovered as well as the
      morphology of the inferior colliculus that was similar to the control group. Our
      results support the hypothesis that antioxidant treatments have a protective
      effect on the functional changes of the auditory pathway and on the morphological
      damage which occurs after HI insult. 

PMID- 25990816
TI  - Determination of the Free Metal Ion Concentration Using AGNES Implemented with
      Environmentally Friendly Bismuth Film Electrodes.
AB  - Ex situ plated Bi film electrodes (Bi-FE) have been employed, for the first time,
      to measure the free concentration of Pb(II) in aqueous solutions using absence of
      gradients and Nernstian equilibrium stripping (AGNES) with stripping
      chronopotentiometry (SCP) quantification. The amount of deposited Pb degrees ,
      below a certain threshold, follows a Nernstian relationship with the applied
      potential. This threshold can be interpreted as the frontier of transition from
      surface deposition to solid (bulk) formation of Pb degrees . AGNES with Bi-FE
      yielded a very good detection limit (3sigma) for Pb(II) of 6.0 * 10(-9) M with an
      applied gain of 398 and a deposition time of 400 s. The ability of the Bi film
      electrode to perform speciation measurements was demonstrated for Pb(II)-PSS and
      Pb(II)-IDA systems. The measured values with the Bi-FE were in good agreement
      with the values obtained using the Hg film electrode and/or the values reported
      in the literature. 

PMID- 25990817
TI  - Influence of the forms and levels of dietary selenium on antioxidant status and
      oxidative stress-related parameters in rainbow trout (Oncorhynchus mykiss) fry.
AB  - Se is an essential micronutrient required for normal growth, development and
      antioxidant defence. The objective of the present study was to assess the impact
      of dietary Se sources and levels on the antioxidant status of rainbow trout
      (Oncorhynchus mykiss) fry. First-feeding fry (initial body weight: 91 mg) were
      fed either a plant- or fishmeal-based diet containing 0.5 or 1.2 mg Se/kg diet
      supplemented or not with 0.3 mg Se/kg diet supplied as Se-enriched yeast or
      sodium selenite for 12 weeks at 17 degrees C. Growth and survival of rainbow
      trout fry were not significantly affected by dietary Se sources and levels. Whole
      body Se was raised by both Se sources and to a greater extent by Se-yeast. The
      reduced:oxidised glutathione ratio was raised by Se-yeast, whereas other lipid
      peroxidation markers were not affected by dietary Se. Whole-body Se-dependent
      glutathione peroxidase (GPX) activity was enhanced in fish fed Se-yeast compared
      to fish fed sodium selenite or non-supplemented diets. Activity and gene
      expression of this enzyme as well as gene expression of selenoprotein P (SelP)
      were reduced in fish fed the non-supplemented plant-based diet. Catalase,
      glutamate-cysteine ligase and nuclear factor-erythroid 2-related factor 2 (Nrf2)
      gene expressions were reduced by Se-yeast. These results suggest the necessity to
      supplement plant-based diets with Se for rainbow trout fry, and highlight the
      superiority of organic form of Se to fulfil the dietary Se requirement and
      sustain the antioxidant status of fish. GPX and SelP expression proved to be good
      markers of Se status in fish. 

PMID- 25990818
TI  - AINSWORTH'S STRANGE SITUATION PROCEDURE: THE ORIGIN OF AN INSTRUMENT.
AB  - The American-Canadian psychologist Mary Ainsworth (1913-1999) developed the
      Strange Situation Procedure (SSP) to measure mother-child attachment and
      attachment theorists have used it ever since. When Ainsworth published the first
      results of the SSP in 1969, it seemed a completely novel and unique instrument.
      However, in this paper we will show that the SSP had many precursors and that the
      road to such an instrument was long and winding. Our analysis of hitherto little
      known studies on children in strange situations allowed us to compare these
      earlier attempts with the SSP. We argue that it was the combination of
      Ainsworth's working experience with William Blatz and John Bowlby, her own
      research in Uganda and Baltimore, and the strong connection of the SSP with
      attachment theory, that made the SSP differ enough from the other strange
      situation studies to become one of the most widely used instruments in
      developmental psychology today. 

PMID- 25990819
TI  - Comparative Development of Embryonic Age by Organogenesis in Domestic Dogs and
      Cats.
AB  - The precise determination of the embryonic chronology is very important in
      reproductive biotechnologies, especially in estimating embryonic age. Thus, there
      is a need for greater knowledge and standardization for determining the
      chronology of embryonic development and functional morphology. We describe
      aspects of embryonic development in two domestic carnivores to add knowledge
      about organ peculiarities and for application in veterinary practice, in prenatal
      development and in the biotechnology fields. We found that the development of
      differential characteristics of embryonic organs occurs in the first trimester of
      pregnancy for both species. Thus, using the combination of the crown-rump length,
      macroscopic analysis and optical microscopy, it is possible to predict
      gestational age more precisely in animals that lack a defined breed and establish
      an embryonic pattern. 

PMID- 25990820
TI  - Ageing and visual spatiotemporal processing.
AB  - Ageing affects many visual functions. Here, we investigated the effects of ageing
      on vernier acuity and backward masking using the shine-through paradigm. We
      divided healthy older adults (>60 years) into two groups depending on whether
      vernier duration was comparable to younger adults (Older Adults 1) or not (Older
      Adults 2). Backward masking was deteriorated for Older Adults 2 but not for Older
      Adults 1. In addition, by using complex masking gratings, we found deficits in
      spatial and temporal vision in Older Adults 2, which cannot be explained by
      deteriorated visual acuity, pointing to cortical rather than retinal causes. Our
      results highlight the importance of taking into account individual differences in
      visual ageing research. In addition, our results have important implications for
      schizophrenia. Schizophrenia has been suggested to be a form of early brain
      ageing. Linking our current masking results in ageing to previous masking results
      in schizophrenia shows that schizophrenia is not a form of early ageing, at least
      not in the visual domain. 

PMID- 25990821
TI  - Proprioception in motor learning: lessons from a deafferented subject.
AB  - Proprioceptive information arises from a variety of channels, including muscle,
      tendon, and skin afferents. It tells us where our static limbs are in space and
      how they are moving. It remains unclear however, how these proprioceptive modes
      contribute to motor learning. Here, we studied a subject (IW) who has lost large
      myelinated fibres below the neck and found that he was strongly impaired in
      sensing the static position of his upper limbs, when passively moved to an unseen
      location. When making reaching movements however, his ability to discriminate in
      which direction the trajectory had been diverted was unimpaired. This
      dissociation allowed us to test the involvement of static and dynamic
      proprioception in motor learning. We found that IW showed a preserved ability to
      adapt to force fields when visual feedback was present. He was even sensitive to
      the exact form of the force perturbation, responding appropriately to a velocity-
      or position-dependent force after a single perturbation. The ability to adapt to
      force fields was also preserved when visual feedback about the lateral
      perturbation of the hand was withdrawn. In this experiment, however, he did not
      exhibit a form of use-dependent learning, which was evident in the control
      participants as a drift of the intended direction of the reaching movement in the
      perturbed direction. This suggests that this form of learning may depend on
      static position sense at the end of the movement. Our results indicate that
      dynamic and static proprioception play dissociable roles in motor learning. 

PMID- 25990822
TI  - Influence of temporal pressure constraint on the biomechanical organization of
      gait initiation made with or without an obstacle to clear.
AB  - Many daily motor tasks have to be performed under a temporal pressure constraint.
      This study aimed to explore the influence of such constraint on motor performance
      and postural stability during gait initiation. Young healthy participants
      initiated gait at maximal velocity under two conditions of temporal pressure: in
      the low-pressure condition, gait was self-initiated (self-initiated condition,
      SI); in the high-pressure condition, it was initiated as soon as possible after
      an acoustic signal (reaction-time condition, RT). Gait was initiated with and
      without an environmental constraint in the form of an obstacle to be cleared
      placed in front of participants. Results showed that the duration of postural
      adjustments preceding swing heel-off ("anticipatory postural adjustments", APAs)
      was shorter, while their amplitude was larger in RT compared to SI. These larger
      APAs allowed the participants to reach equivalent postural stability and motor
      performance in both RT and SI. In addition, the duration of the execution phase
      of gait initiation increased greatly in the condition with an obstacle to be
      cleared (OBST) compared to the condition without an obstacle (NO OBST), thereby
      increasing lateral instability and thus involving larger mediolateral APA.
      Similar effects of temporal pressure were obtained in NO OBST and OBST. This
      study shows the adaptability of the postural system to temporal pressure in
      healthy young adults initiating gait. The outcome of this study may provide a
      basis for better understanding the aetiology of balance impairments with the risk
      of falling in frail populations while performing daily complex tasks involving a
      whole-body progression.

PMID- 25990823
TI  - A one-step approach to the large-scale synthesis of functionalized MoS2
      nanosheets by ionic liquid assisted grinding.
AB  - A prerequisite for exploiting most proposed applications for MoS2 is the
      availability of water-dispersible functionalized MoS2 nanosheets in large
      quantities. Here we report one-step synthesis and surface functionalization of
      MoS2 nanosheets by a facile ionic liquid assisted grinding method in the presence
      of chitosan. The selected ionic liquid with suitable surface energy could
      efficiently overcome the van der Waals force between the MoS2 layers. Meanwhile,
      chitosan molecules bind to the plane of MoS2 sheets non-covalently, which
      prevents the reassembling of exfoliated MoS2 sheets and facilitates the
      exfoliation progress. The obtained chitosan functionalized MoS2 nanosheets
      possess favorable stability and biocompatibility, which renders them as promising
      and biocompatible near-infrared agents for photothermal ablation of cancer. This
      contribution provides a facile way for the green, one-step and large-scale
      synthesis of advanced functional MoS2 materials. 

PMID- 25990824
TI  - Is it useful to also image the asymptomatic leg in patients with suspected deep
      vein thrombosis?: comment.

PMID- 25990825
TI  - The Economic Burden of PTSD in Northern Ireland.
AB  - The objective of this study was to estimate the economic costs of posttraumatic
      stress disorder (PTSD) among the Northern Ireland (NI) adult population. The
      authors present a prevalence-based, bottom-up study based primarily on data from
      1,986 participants in the Northern Ireland Study of Health and Stress (NISHS).
      Both direct costs of treatment and indirect costs of productivity losses were
      included. Units of service and medication resource use were obtained from the
      NISHS and combined with their relevant unit costs from the Personal Social
      Services Research Unit and Prescription Costs Analysis data for NI. Indirect
      costs included the costs of incapacity days due to PTSD and presenteeism costs,
      with gender-specific wage rates used as the relevant unit costs. The total direct
      and indirect cost of PTSD in NI (2008) was L172,756,062. This figure is likely to
      be conservative due to the exclusion of a number of cost categories.
      Nevertheless, comparison of estimates of the burden of PTSD with the estimated
      cost of treating all adults with PTSD with the recommended treatments shows the
      potential for substantial economic gains to be made through extension and
      investment in effective evidence-based treatments. 

PMID- 25990826
TI  - Clinical profile and quality of life of patients with occupational contact
      dermatitis from New Delhi, India.
AB  - BACKGROUND: Data regarding occupational contact dermatitis (OCD) and its effect
      on quality of life (QOL) in India are limited. OBJECTIVES/AIMS: To evaluate
      patients with OCD and record the outcome of treatment.
      PATIENTS/MATERIALS/METHODS: All patients with OCD were evaluated for severity of
      disease (by the use of physician global assessment) and its effect on QOL (by use
      of the Dermatology Life Quality Index) questionnaire) at the first visit and
      after 3 months of treatment. RESULTS: Among 117 patients with OCD, hand eczema
      was present in 81.2%. Positive patch test reactions were found in 76%. The most
      common allergens were Parthenium hysterophorus and potassium dichromate. The most
      frequent diagnosis was occupational allergic contact dermatitis (OACD) (57%),
      caused by farming and construction work, followed by occupational irritant
      contact dermatitis (OICD) (24%), caused by wet work. Severe psychosocial distress
      was recorded in 62.5% of patients. After 3 months of treatment, 83% improved
      significantly, and 54% had improvement in QOL. CONCLUSIONS: Farmers were most
      frequently affected, followed by construction workers and housewives. OACD was
      found at a higher frequency than OICD. The most frequent allergens were
      Parthenium hysterophorus in farmers, potassium dichromate in construction
      workers, and vegetables in housewives. OCD has a significant impact on QOL. Patch
      testing, in addition to standard treatment, improves the outcome considerably.

PMID- 25990827
TI  - Evaluation of wavelet performance via an ANN-based electrical conductivity
      prediction model.
AB  - The prediction of water quality parameters plays an important role in water
      resources and environmental systems. The use of electrical conductivity (EC) as a
      water quality indicator is one of the important parameters for estimating the
      amount of mineralization. This study describes the application of artificial
      neural network (ANN) and wavelet-neural network hybrid (WANN) models to predict
      the monthly EC of the Asi River at the Demirkopru gauging station, Turkey. In the
      proposed hybrid WANN model, the discrete wavelet transform (DWT) was linked to
      the ANN model for EC prediction using a feed-forward back propagation (FFBP)
      training algorithm. For this purpose, the original time series of monthly EC and
      discharge (Q) values were decomposed to several sub-time series by DWT, and these
      sub-time series were then presented to the ANN model as an input dataset to
      predict the monthly EC. Comparing the values predicted by the models indicated
      that the performance of the proposed WANN model was better than the conventional
      ANN model. The correlation of determination (R (2)) were 0.949 and 0.381 for the
      WANN and ANN models, respectively. The results indicate that the peak EC values
      predicted by the WANN model are closer to the observed values, and this model
      simulates the hysteresis phenomena at an acceptable level as well. 

PMID- 25990828
TI  - Pilot study on the effects of high molecular weight sodium hyaluronate in the
      treatment of chronic pharyngitis.
AB  - Although several therapeutic approaches are available at present for the
      treatment of chronic pharyngitis, new therapeutic strategies acting on pharyngeal
      mucous function should be investigated in order to improve symptoms and quality
      of life. High-molecular weight hyaluronate performs important functions on
      mucociliary clearance, tissues hydration, defense against micro-organisms, and on
      tissue repair as well, but at present there is no clinical evidence of its
      exogenous use in patients with chronic pharyngitis. Our open, randomized
      controlled study was carried out to investigate efficacy, and tolerability of
      exogenous high molecular weight sodium hyaluronate (SH) at the dosage of 9 mg
      three times a day for a period of 30 days, in patients with chronic pharyngitis.
      Results show significant improvements of symptoms and cytology in active group
      (A, n = 10) vs. control group (B, n = 10). Good compliance and no adverse events
      were reported in group A. In conclusion, SH was effective and safe in patients
      with chronic pharyngitis. 

PMID- 25990829
TI  - Estimation of gestational age from gall-bladder length.
AB  - Establishing a precise duration of gestation is vital in situations such as
      infanticide and criminal abortions. The present study attempted to estimate the
      gestational age of the foetus from gall-bladder length. Foetuses of various
      gestational age groups were dissected, and the length of the gall bladder was
      measured. The results were analysed, and a substantial degree of correlation was
      statistically confirmed. This novel method is helpful when the foetus is
      fragmented, putrefied or eviscerated, where this method can be used as an
      additional parameter to improve the accuracy of foetal age estimation. 

PMID- 25990830
TI  - Curtailing Oxidation-Induced Loss of Myosin Gelling Potential by Pyrophosphate
      Through Shielding the S1 Subfragment.
AB  - In muscle food processing, where oxidation is inevitable, phosphates are usually
      added to improve water binding. This present study attempted to investigate the
      interactive roles of protein oxidation and pyrophosphate (PP) during thermal
      gelation of myosin. Myosin isolated from pork muscle was solubilized in 0.5 M
      NaCl at pH 6.2 then oxidatively stressed with an iron-redox cycling system that
      produces hydroxyl radicals with or without 1 mM PP and 2 mM MgCl2 at 4  degrees C
      for 12 or 24 h then heated to 50  degrees C at 1.3  degrees C/min. Protein
      conformational stability was measured by differential scanning calorimetry, and
      covalent cross-linking was examined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis following chymotrypsin digestion. The binding of PP to myosin
      suppressed disulfide bond formation in myosin subfragments 1 and 2 and partially
      inhibited oxidation-initiated cross-linking of heavy meromyosin during myosin
      gelation with a lesser effect on light meromyosin. In the presence of PP, myosin
      exhibited less loss of conformational integrity upon oxidation than myosin
      without PP. Rheological analysis from 20 to 75  degrees C indicated up to 32%
      decreases (P < 0.05) in elastic modulus (G') of myosin gels due to oxidation.
      However, the presence of 1 mM PP, which also lowered the gelling capacity of
      myosin, inhibited the oxidation-induced G' by nearly half (P < 0.05). These
      results suggest that the protection of myosin head from oxidative modification by
      PP can be a significant factor for the minimization of gelling property losses
      during cooking of comminuted meats. PRACTICAL APPLICATION: The association of
      myosin S1 subfragment possibly S2 as well with pyrophosphate prevents extensive
      myosin head-head cross-linking. This alleviates the negative impact of oxidation
      on the gel formation of myosin, an expected main form of myofibrillar protein due
      to pyrophosphate-induced actomyosin dissociation. Likewise, oxidative S1-S1
      association inhibits the binding of pyrophosphate thereby reducing its gel
      weakening effect. The mutual constraining roles of oxidation and pyrophosphate
      can be a significant factor for the minimization of gelling property losses
      during the manufacture of comminuted meat products.

PMID- 25990835
TI  - Particle-based technologies for osteoarthritis detection and therapy.
AB  - Osteoarthritis (OA) is a disease characterized by degradation of joints with the
      development of painful osteophytes in the surrounding tissues. Currently, there
      are a limited number of treatments for this disease, and many of these only
      provide temporary, palliative relief. In this review, we discuss particle-based
      drug delivery systems that can provide targeted and sustained delivery of imaging
      and therapeutic agents to OA-affected sites. We focus on technologies such as
      polymeric micelles and nano-/microparticles, liposomes, and dendrimers for their
      potential treatment and/or diagnosis of OA. Several promising studies are
      highlighted, motivating the continued development of delivery technologies to
      improve treatments for OA. 

PMID- 25990837
TI  - Role of endothelin-1 in the skin fibrosis of systemic sclerosis.
AB  - Endothelin-1 (ET-1) acts as a key regulator of vasoconstriction and fibrosis.
      Many previous studies have focused on the role of ET-1 in scleroderma (systemic
      sclerosis, SSc). We investigated the effects of ET-1 on the production of
      extracellular matrix in SSc and normal skin fibroblasts. Primary cultured dermal
      fibroblasts from SSc patients and healthy controls were treated with ET-1 (25
      ng/mL) for 0 min, 15 min, 1 h, 24 h, 48 h and 72 h, respectively. Our results
      showed that, in SSc fibroblasts, ET-1 upregulated collagen type I, connective
      tissue growth factor (CTGF), type I plasminogen activator inhibitor (PAI-1) and
      pAkt in a time-dependent manner within 72 h; in normal fibroblasts, 25 ng/mL ET-1
      stimulation correlated with high levels of CTGF, PAI-1 and pAkt. The secretion of
      fibronectin (FN), collagen type I, and PAI-1 is markedly increased in the
      supernatant of both SSc fibroblasts and normal fibroblasts. Furthermore, ET-1
      phosphorylates Smad2 and Smad3 in normal fibroblasts, but not in SSc fibroblasts.
      In conclusion, our results demonstrated that ET-1 may induce fibrosis in dermal
      fibroblasts through Akt signals.

PMID- 25990838
TI  - What is epistemic value in free energy models of learning and acting? A bounded
      rationality perspective.
AB  - Free energy models of learning and acting do not only care about utility or
      extrinsic value, but also about intrinsic value, that is, the information value
      stemming from probability distributions that represent beliefs or strategies.
      While these intrinsic values can be interpreted as epistemic values or
      exploration bonuses under certain conditions, the framework of bounded
      rationality offers a complementary interpretation in terms of information
      processing costs that we discuss here. 

PMID- 25990836
TI  - Stem and progenitor cells: advancing bone tissue engineering.
AB  - Unlike many other postnatal tissues, bone can regenerate and repair itself;
      nevertheless, this capacity can be overcome. Traditionally, surgical
      reconstructive strategies have implemented autologous, allogeneic, and prosthetic
      materials. Autologous bone--the best option--is limited in supply and also
      mandates an additional surgical procedure. In regenerative tissue engineering,
      there are myriad issues to consider in the creation of a functional, implantable
      replacement tissue. Importantly, there must exist an easily accessible, abundant
      cell source with the capacity to express the phenotype of the desired tissue, and
      a biocompatible scaffold to deliver the cells to the damaged region. A literature
      review was performed using PubMed; peer-reviewed publications were screened for
      relevance in order to identify key advances in stem and progenitor cell
      contribution to the field of bone tissue engineering. In this review, we briefly
      introduce various adult stem cells implemented in bone tissue engineering such as
      mesenchymal stem cells (including bone marrow- and adipose-derived stem cells),
      endothelial progenitor cells, and induced pluripotent stem cells. We then discuss
      numerous advances associated with their application and subsequently focus on
      technological advances in the field, before addressing key regenerative
      strategies currently used in clinical practice. Stem and progenitor cell
      implementation in bone tissue engineering strategies have the ability to make a
      major impact on regenerative medicine and reduce patient morbidity. As the field
      of regenerative medicine endeavors to harness the body's own cells for treatment,
      scientific innovation has led to great advances in stem cell-based therapies in
      the past decade.

PMID- 25990839
TI  - Identification of new cases of severe enteropathy has recently increased the
      spectrum of intestinal non-celiac villous atrophy.
AB  - From olmesartan-induced enteropathy to small CD4(+) T-cell intestinal
      lymphoproliferation, the spectrum of non-celiac villous atrophy has recently been
      largely extended. Precise characterization of the different types of non-celiac
      enteropathy with villous atrophy is necessary to avoid misdiagnosis, to identify
      a causal mechanism and propound appropriate therapeutic strategies. This paper
      discusses how to use the different diagnostic tools to address diagnostic
      criteria, citing the examples of recent new cases of non-celiac enteropathy with
      intestinal villous atrophy. 

PMID- 25990840
TI  - Gun Violence Restraining Orders: Alternative or Adjunct to Mental Health-Based
      Restrictions on Firearms?
AB  - The gun violence restraining order (GVRO) is a new tool for preventing gun
      violence. Unlike traditional approaches to prohibiting gun purchase and
      possession, which rely on a high threshold (adjudication by criminal justice or
      mental health systems) before intervening, the GVRO allows family members and
      intimate partners who observe a relative's dangerous behavior and believe it may
      be a precursor to violence to request a GVRO through the civil justice system.
      Once issued by the court, a GVRO authorizes law enforcement to remove any guns in
      the respondent's possession and prohibits the respondent from purchasing new
      guns. In September 2014, California's governor signed AB1014 into law, making
      California the first U.S. state to enact a GVRO law. This article describes the
      GVRO and the rationale behind the concept, considers case examples to assess the
      potential impact of the GVRO as a strategy for preventing gun violence, and
      reviews the content of the California law.

PMID- 25990841
TI  - Exploring drive for thinness as a perfectionistic strategy to escape from shame
      experiences.
AB  - Perfectionistic self-presentation defines the attempt at presenting the self as
      perfect through the public concealment of personal defects and/or through the
      display of attributes perceived as capable to gather positive attention of
      others. Although perfectionism has long been considered a central aspect of
      eating psychopathology mediational studies between this construct and these
      conditions are scarce. This study aimed at examining the mediational role of body
      image-related perfectionistic self-presentation in the effects of external shame
      and internal shame on drive for thinness, in a sample of young women. Results
      revealed body image-related perfectionistic self-presentation as a significant
      mediator (p < .05) of the relationships between external and internal shame, and
      drive for thinness. Furthermore, 86% and 69% of the effects of external shame and
      internal shame, respectively, were explained by their indirect effects through
      body image-related perfectionistic self-presentation on drive for thinness (95%
      CI). These results highlight that the control over eating may emerge as a
      maladaptive strategy to deal with shame when mediated by an endorsement in the
      belief that presenting a perfect body image is crucial to be accepted and valued
      by others. Study findings suggest that this perfectionistic strategy should be
      targeted while treating eating psychopathology. 

PMID- 25990842
TI  - Microarray Approach to Identify the Signaling Network Responsible for Self
      Renewal of Human Embryonic Stem Cells.
AB  - Here we introduce the representative method to culture HESCs under the feeder and
      feeder-free conditions, the former of which is used to maintain or expand
      undifferentiated HESCs, and the latter can be used for the preparation of pure
      HESCs RNA samples, or for screening factors influential on self-renewal of HESCs.
      We also describe a protocol and tips for conducting gene chip analysis focusing
      on widely used Affymetrix Microarrays. These techniques will provide us
      unprecedented scale of biological information that would illuminate a key to
      decipher complex signaling networks controlling pluripotency. 

PMID- 25990843
TI  - Association Between Disrespect and Abuse During Childbirth and Women's Confidence
      in Health Facilities in Tanzania.
AB  - OBJECTIVES: In Tanzania, maternal mortality is high and coverage with health
      facility delivery low, despite efforts to reduce barriers to utilization.
      Disrespect and abuse during childbirth has not been explored as a contributor to
      delivery satisfaction or as a deterrent to institutional delivery. We assessed
      the association between reported disrespectful treatment during childbirth and
      delivery satisfaction, perceived quality of care, and intention to deliver at the
      same facility in the future. METHODS: Interviews using a structured questionnaire
      were conducted in Tanga Region, Tanzania with women on discharge from delivery at
      two hospitals. Disrespect and abuse was measured by asking women about specific
      disrespectful events during childbirth. Multivariable logistic regression models
      were used to assess the association between disrespect/abuse and (1) satisfaction
      with delivery, (2) perceived quality of care for delivery, and (3) intent to use
      the same facility for a future delivery, controlling for confounders. RESULTS:
      1388 women participated in the survey (67 % response rate). Disrespect/abuse
      during childbirth was associated with lower satisfaction with delivery (OR 0.26,
      95 % CI 0.19-0.36) and reduced likelihood of rating perceived quality of care as
      excellent/very good (OR 0.55, 95 % CI 0.35-0.85). Of women who planned to have
      more children (N = 766), those who experienced disrespect/abuse were half as
      likely to plan to deliver again at the same facility (OR 0.51, 95 % CI 0.32
      0.82). CONCLUSIONS: Our study highlights disrespectful and abusive treatment
      during childbirth as an important factor in reducing women's confidence in health
      facilities. Improving interpersonal care must be an integral part of quality
      improvement in maternal health.

PMID- 25990844
TI  - The recipient celiac trunk as an alternative to the native hepatic artery for
      arterial reconstruction in adult liver transplantation.
AB  - During liver transplantation (LT), the recipient hepatic artery (RHA) cannot
      always be used, and alternatives include aortohepatic conduits and the splenic
      artery (SA). We report our experience with arterial reconstruction on the
      recipient celiac trunk (RCT), which has rarely been described. Since January
      2013, we have been using the RCT when the RHA could not be used. All cases were
      discussed in a multidisciplinary LT meeting, and arterial patency or anomalies
      were systemically viewed with computed tomography (CT) scan. The RCT was used
      after section-ligation of all celiac trunk collaterals. Until May 2014, the RHA
      could not be used in 11/139 (8%) patients who underwent LT. Postoperative
      arterial patency was assessed by serial Doppler ultrasound and CT scan. The
      advantages and disadvantages of the different arterial conduits were evaluated.
      The RCT was used in 7/11 (64%) patients. Mean follow-up was 10 (6-15) months. The
      patency rate was 100%, and 1 patient with associated portal shunting died at day
      20 from septic complications. No related gastric or splenic complications were
      encountered. The RCT could not be used in 4 patients with reconstruction on the
      SA (n = 2), infrarenal (n = 1), and supraceliac aorta (n = 1). The patency rate
      was 75%. One patient with SA conduit and portal shunting developed
      pancreatitis/anastomotic pseudoaneurysm with secondary rupture. An emergency
      infrarenal conduit was created, which was later embolized because of infected
      pseudoaneurysms. Although the literature reports a higher risk of thrombosis with
      aortohepatic conduits, no long-term results are available for the SA conduits,
      and only 1 report is available for the RCT. In conclusion, this study shows that
      the RCT is a good alternative to the RHA and can be used in two-thirds of
      patients with inadequate RHA flow.

PMID- 25990846
TI  - Treatment outcome and patterns of failure in patients of non-pineal
      supratentorial primitive neuroectodermal tumor: review of literature and clinical
      experience form a regional cancer center in north India.
AB  - BACKGROUND: Supra-tentorial primitive neuroectodermal tumors (SPNET) are high
      grade, hemispheric tumors, which account for around 2-3 % of pediatric brain
      tumors. We herein intend to report the clinical features and treatment outcome of
      patients with nonpineal SPNET treated at our institute. METHODS: Clinical data
      were collected by retrospective chart review from 2006 to 2012. Histopathology
      slides were reviewed, and relevant immunohistochemistry stains were done. Overall
      survival (OS), recurrence-free survival (RFS) and event-free survival (EFS) were
      analyzed by the Kaplan-Meier product-limit method. RESULTS: Fifteen patients met
      the study criterion (male: female = 2:1). Median age at presentation was 11 years
      (range 3-49 years). Surgical resection was gross total in 6 (40%) and subtotal in
      8 (53.33%) patients. At presentation, two patients had leptomeningeal
      dissemination. Radiation therapy was delivered in 11 (73.33%) patients:
      craniospinal irradiation in 8 (36 Gy/20 fractions/4 weeks to the craniospinal
      axis followed by a local boost of 20 Gy/10 fractions/2 weeks) and focal RT in 3
      patients. Systemic chemotherapy (median 6 cycles; range 1-16 cycles), given in 13
      (86.67%) patients, included the VAC regimen (vincristine, adriamycin,
      cyclophosphamide) alternating with IE (ifosfamide,etoposide). After a median
      follow-up of 22.6 months (mean, 24.47 months), complete response and progressive
      disease were noted in 8 (53.33%) and 7 (46.67%) patients, respectively. Median OS
      was not reached, and estimated median EFS was noted to be 4.12 years (actuarial
      rate of EFS at 2 years, 55.2%). CONCLUSION: Maximal safe resection followed by
      craniospinal irradiation and systemic chemotherapy with 6-12 cycles of an
      alternating regimen of VAC and IE is a reasonable treatment strategy in patients
      with nonpineal SPNET.

PMID- 25990845
TI  - PRRSV-infected monocyte-derived dendritic cells express high levels of SLA-DR and
      CD80/86 but do not stimulate PRRSV-naive regulatory T cells to proliferate.
AB  - In vitro generated monocyte-derived dendritic cells (moDCs) have frequently been
      used to study the influence of porcine reproductive and respiratory syndrome
      virus (PRRSV) infection on antigen presenting cells. However, obtained results
      have often been conflicting in regard to expression of co-stimulatory molecules
      and interaction with T cells. In this study we performed a detailed phenotypic
      characterisation of PRRSV-infected moDCs and non-infected moDCs. For CD163 and
      CD169, which are involved in PRRSV-entry into host cells, our results show that
      prior to infection porcine moDCs express high levels of CD163 but only very low
      levels for CD169. Following infection with either PRRSV-1 or PRRSV-2 strains
      after 24 h, PRRSV-nucleoprotein (N-protein)(+) and N-protein(-) moDCs derived
      from the same microculture were analyzed for expression of swine leukocyte
      antigen-DR (SLA-DR) and CD80/86. N-protein(+) moDCs consistently expressed higher
      levels of SLA-DR and CD80/86 compared to N-protein(-) moDCs. We also investigated
      the influence of PRRSV-infected moDCs on proliferation and frequency of Foxp3(+)
      regulatory T cells present within CD4(+) T cells in in vitro co-cultures. Neither
      CD3-stimulated nor unstimulated CD4(+) T cells showed differences in regard to
      proliferation and frequency of Foxp3(+) T cells following co-cultivation with
      either PRRSV-1 or PRRSV-2 infected moDCs. Our results suggest that a more
      detailed characterisation of PRRSV-infected moDCs will lead to more consistent
      results across different laboratories and PRRSV strains as indicated by the major
      differences in SLA-DR and CD80/86 expression between PRRSV-infected and non
      infected moDCs present in the same microculture. 

PMID- 25990847
TI  - Electromagnetic navigation-guided surgery in the semi-sitting position for
      posterior fossa tumours: a safety and feasibility study.
AB  - BACKGROUND: Electromagnetic (EM)-guided neuronavigation is an innovative
      technique and a viable alternative to opto-electric navigation. We have performed
      a safety and feasibility study using EM-guided neuronavigation for posterior
      fossa surgery in the semi-sitting position in a selected subset of patients.
      METHODS: Out of 284 patients with posterior fossa tumours operated upon over a
      period of 40 months, a subset of 15 patients was thought to possibly benefit from
      EM navigational guidance and was included in this study. There were six children
      and nine adults (aged between 8 and 84 years; mean age, 34.6 years) with
      different neoplasms in the brainstem or close to the midline. All patients had
      contrast-enhanced three-dimensional (3D) magnetic resonance imaging (MRI) of the
      head preoperatively. EM-guided navigation was used to identify and preserve the
      venous sinuses during craniotomy and to determine the trajectory to the lesion
      using various approaches. Neuronavigation accuracy was repeatedly checked for
      deviations measured in millimetres on screen shots during surgery before and
      after dural opening in the coronal (z = vertical), axial (x = mediolateral) and
      sagittal (y = anteroposterior) plane. RESULTS: Referencing of the patient in the
      supine position was fast and easy. There was no loss of navigation accuracy after
      repositioning of the patient in the semi-sitting position (mean, 2.5 mm +/- 0.92
      mm). Identification of the pathological structure using EM navigation was
      achieved in all instances. Optimal angulation of the neck was selected
      individually to permit a comfortable position for the surgeon with full access to
      the lesion avoiding over-flexion. Deviation of accuracy at the surface of the
      target lesion ranged between 2.5 and 5.8 mm (mean, 3.9 mm +/- 1.1 mm).
      CONCLUSIONS: EM-guided neuronavigation in the semi-sitting position was safe and
      technically feasible. It enabled fast and accurate referencing without loss of
      navigation accuracy despite repositioning of the patient. In contrast to
      conventional opto-electric neuronavigation there were no line of sight problems.

PMID- 25990848
TI  - An examination of retention factors among registered practical nurses in north
      eastern Ontario, Canada.
AB  - INTRODUCTION: Literature from the past two decades has presented an insufficient
      amount of research conducted on the nursing practice environments of registered
      practical nurses (RPNs). The objective of this article was to investigate the
      barriers and facilitators to sustaining the nursing workforce in north-eastern
      Ontario (NEO), Canada. In particular, retention factors for RPNs were examined.
      METHODS: This cross-sectional research used a self-administered questionnaire.
      Home addresses of RPNs working in NEO were obtained from the College of Nurses of
      Ontario (CNO). Following a modified Dillman approach with two mail-outs, survey
      packages were sent to a random sample of RPNs (<i>N</i>=1337) within the NEO
      region. Logistic regression analyses were used to determine intent to stay (ITS)
      in relation to the following factor categories: demographic, and job and career
      satisfaction. RESULTS: Completed questionnaires were received from 506
      respondents (37.8% response rate). The likeliness of ITS in the RPNs' current
      position for the next 5 years among nurses aged 46-56 years were greater than
      RPNs in the other age groups. Furthermore, the lifestyle of NEO, internal staff
      development, working in nursing for 14-22.5 years, and working less than 1 hour
      of overtime per week were factors associated with the intention to stay.
      CONCLUSIONS: Having an understanding of the work environment may contribute to
      recruitment and retention strategy development. The results of this study may
      assist with addressing the nursing shortage in rural and northern areas through
      improved retention strategies of RPNs.

PMID- 25990849
TI  - Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: an
      in vivo study.
AB  - To date, several small molecule inhibitors and monoclonal-antibodies (like ICR
      62) have been used to treat tumors over-expressing epidermal growth factor
      receptor (EGFR). However, the limitations associated with these conventional
      applications accentuate the necessity of alternative approaches. Mimotopes as
      compelling molecular tools could rationally be employed to circumvent these
      drawbacks. In the present study, an M13 phage displaying ICR-62 binding peptide
      mimotope is exploited as a vaccine candidate. It exhibited high affinity towards
      ICR62 and polyclonal anti-P-BSA antibodies. Following the mice immunization,
      phage-based mimotope vaccine induced humoral immunity. Elicited anti-EGFR
      mimotope antibodies were detected using ELISA method. Moreover, the phage vaccine
      was tested on the Lewis lung carcinoma mice model to investigate the prophylactic
      and therapeutic effects. The tumor volume was measured and recorded in different
      animal groups to evaluate the anti-tumor effects of the vaccine. Our data
      indicate that the reported phage-based mimotope could potentially elicit specific
      antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor
      growth. However, in vivo experiments of prophylactic or therapeutic vaccination
      showed no specific advantage. Furthermore, phage-mimotope vaccine might be a
      promising approach in the field of cancer immunotherapy. 

PMID- 25990850
TI  - Anti-inflammatory and antioxidant effects of coumarins isolated from Foeniculum
      vulgare in lipopolysaccharide-stimulated macrophages and 12-O
      tetradecanoylphorbol-13-acetate-stimulated mice.
AB  - CONTEXT: Foeniculum vulgare (F. vulgare) is traditionally used to treat
      inflammatory diseases. Recently, anti-inflammatory and antioxidant activities of
      methanol extract of the fruits of F. vulgare were reported. To identify
      biologically active compounds responsible for the anti-inflammatory activity, we
      isolated four coumarins, scopoletin, 8-methoxypsoralen, bergapten and imperatorin
      from the fruits of F. vulgare. OBJECTIVE: This study assessed the anti
      inflammatory and antioxidant effects of coumarins isolated from F. vulgare in
      lipopolysaccharide (LPS)-stimulated macrophages and 12-O-tetradecanoylphorbol-13
      acetate (TPA)-stimulated mice. MATERIALS AND METHODS: RAW 264.7 cells were
      treated with the coumarins (30 uM) and then stimulated with LPS (100 ng/ml). Ears
      of ICR mice were treated with TPA (1 ug/ear) once a day. Ten microliters each of
      the four coumarins (200 MUg/ml) were topically applied to the ears for 3 days.
      Antioxidant activities were examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      and 2,2'-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) scavenging
      assays. RESULTS: All the tested coumarins showed excellent antioxidant activities
      in DPPH and ABTS radical scavenging assays. Among the coumarins, imperatorin had
      the greatest anti-inflammatory activities as measured by inhibition of the pro
      inflammatory cytokines production including interleukin (IL)-6 and tumor necrosis
      factor (TNF)-alpha in LPS-stimulated RAW 264.7 cells through blockade of the
      IkappaB kinase (IKK)/inhibitor of kappa B (IkappaB)/nuclear factor-kappaB (NF
      kappaB) pathway. In vivo experiments showed that imperatorin reduced TPA-induced
      ear thickness/weight, cutaneous cytokines expression and improved
      histopathological features. CONCLUSION: Although four coumarins isolated from the
      fruits of F. vulgare provide effective anti-inflammatory and antioxidant
      activities, imperatorin is most potent.

PMID- 25990851
TI  - Presumptive Q fever myocarditis associated with Coxiella burnetii infection of a
      homograft valve in the outflow tract of the right ventricle: review and case
      report.
AB  - A man with pulmonary atresia and a subaortic ventricular septal defect had a
      radical surgical repair at the age of 16 years with correction of pulmonary
      atresia by replacement with an aortic valve homograft. This later became infected
      with Coxiella burnetii. He died at the age of 27 years from renal failure caused
      by glomerulonephritis and was found to have a most unusual form of widespread
      focal myocardial degeneration with dystrophic calcification. The diagnosis of Q
      fever was confirmed by positive serology during life and identification of the
      organisms in the homograft valve after death, by histology and electron
      microscopy. A fatal outcome from involvement of the myocardium in Q fever is very
      rare, and histological evidence of such involvement, other than by embolic
      infarction, is almost unknown. This would also appear to be the first recorded
      instance of coxiella colonization of a valve in the pulmonary outflow tract. 

PMID- 25990852
TI  - Specialized membrane contacts between immunocompetent cells in human
      atherosclerotic plaques.
AB  - Several immunohistochemical studies have revealed closely apposed T cells and
      macrophages in the various developmental stages of atherosclerosis. The present
      ultrastructural study was undertaken to evaluate the morphologic features of the
      cell-cell contacts of immunocompetent cells and smooth muscle cells in human
      atherosclerotic plaques. Sixteen biopsies were taken at autopsy from small raised
      plaques in the coronary and carotid arteries. Four sites (coronary artery 2,
      carotid artery 2), each with a cell-rich lesion, were selected for
      ultrastructural evaluation. Close contacts between macrophages and lymphocytes
      could be detected in the superficial parts of the atherosclerotic plaque and the
      adjacent thickened intima but were absent in the deeper parts of the plaque.
      Close examination of these cellular contacts revealed lymphocytes partially
      engulfed by macrophages, intermingling of cytoplasmic extensions of both cells,
      and deep extensions of cells in clathrin-coated pits of apposed cells. In
      addition, contacts occurred involving only lymphocytes and only macrophages.
      Membrane contacts between smooth muscle cells and mononuclear cells were absent.
      The occurrence of these specialized membrane contacts provides additional support
      for a role of activated T cells and macrophages in atherosclerosis. The
      interactions among immunocompetent cells suggest their involvement in an immune
      regulatory process. The absence of specialized contacts between smooth muscle
      cells and mononuclear cells implies that they probably are influenced in a
      paracrine way only. 

PMID- 25990853
TI  - Myocyte interconnections at gap junctions and the development of anatomic
      substrates of ventricular arrhythmia's.
AB  - Spontaneous ventricular tachyarrhythmias causing sudden death occur often in
      patients with healed myocardial infarcts. A reentrant mechanism has been
      implicated that depends, in part, on slow heterogeneous conduction and block in
      critical regions that have been mapped to the borders of the healed infarcts. The
      electrophysiological derangements responsible for initiation and maintenance of
      the reentrant tachycardia circuit appear to be attributable largely to
      abnormalities in current transfer between myocytes in the fibrotic border zone
      region. This review summarizes recent advances in understanding the role of gap
      junctions in intercellular electrical coupling in the normal heart and mechanisms
      of altered junctional coupling in the pathogenesis of reentrant ventricular
      tachycardia. 

PMID- 25990854
TI  - Cocaine-induced transmural myocardial infarction in a Yorkshire swine with normal
      coronary arteries: Evidence for microvascular and/or epicardial coronary artery
      spasm.
AB  - Cocaine-induced myocardial infarction with normal coronary arteries is well
      documented in humans. The exact mechanism of action remains speculative. We
      report one case of cocaine-induced myocardial infarction with normal coronaries
      in one swine. Systemic hemodynamics and angiographic, electrocardiographic,
      echocardiographic, and histopathologic data are presented. Intravenous cocaine
      (1, 3, 10 mg/kg) produced significant decreases in mean arterial pressure, heart
      rate, stroke volume, coronary blood flow, and coronary reserve, whereas pulmonary
      artery diastolic pressure and coronary vascular resistances increased. Left
      anterior descending and left circumflex coronary artery cross-sectional area
      decreased by 31% and 64%, respectively, without localized vasospasm.
      Electrocardiographic changes occurred (3 mm ST elevation in leads II, III, AVF).
      Peak creatine phosphokinase was 17,220 IU/L. The echocardiogram revealed severe
      hypokinesis of the inferior wall and normal ventricular function. The animal
      survived the acute phase of the infarction and the swine was restudied 12 weeks
      later. Upon rechallenge, systemic and coronary hemodynamics shoved changes
      similar to those in the previous study. The swine developed ventricular
      fibrillation and expired after the 10 mg/kg cocaine dose. Macroscopic examination
      of the external surface of the heart revealed marked diffuse fibrosis in the
      posteroinferior and lateral left ventricular wall. Our data suggest that the
      infarct induced by cocaine may have resulted from severe vasoconstriction or
      spasm at the level of the microcirculation, and/or the epicardial coronary
      arteries, which shoved slight but significant narrowing throughout their lengths.

PMID- 25990855
TI  - Exercise as a factor in sudden cardiac death.

PMID- 25990856
TI  - Pathobiology of sudden death: coronary causes.
AB  - The single most common cause of sudden death in the western world is coronary
      artery disease. Sudden death from coronary causes occurs equally in asymptomatic
      patients, patients with angina, and patients with a known history of myocardial
      infarction. The mechanism of sudden coronary death in most patients is
      ventricular fibrillation secondary to ischemia. Microthrombi in intramyocardial
      coronary arteries may also play a role. Instability of atherosclerotic plaques,
      in terms of thrombosis and vasoreactivity, underlies the syndrome of unstable
      angina as well as many cases of acute myocardial infarction. Sudden coronary
      death falls within this spectrum of ischemic heart disease. Development of these
      syndromes depends on the abruptness of onset and the completeness and duration of
      coronary occlusion. Thus a rapidly evolving coronary artery lesion, with plaque
      fissure, rupture, and luminal thrombosis, can lead to myocardial ischemia, with
      fatal electrical instability of the myocardium as the first clinical
      manifestation. The diagnosis of sudden coronary death in the absence of
      myocardial infarction is determined by the degree of coronary artery narrowing
      and the exclusion of other causes of death. The presence of acute coronary artery
      lesions, which may be present in a significant number of sudden coronary death
      patients, lends support to the pathologic diagnosis. Thus the coronary arteries
      in victims of sudden coronary death may exhibit established atherosclerotis or
      acute lesions, whereas the myocardium may appear normal or show healed or acute
      infarction or hypertrophy. Although less common, nonatherosclerotic coronary
      artery diseases can account for sudden death as well, particularly in younger
      patients. Therefore, when sudden death occurs in children and young adults,
      coronary causes related to congenital anomalies, fibromuscular dysplasia,
      arteritis, or metabolic diseases should be considered. 

PMID- 25990857
TI  - Sudden death in athletes-Conduction system: Practical approach to dissection and
      pertinent pathology.
AB  - Sudden death does occur in athletes with or without a previous history of
      arrhythmias. A study of the conduction system is mandatory in these individuals
      after ruling out all possible causes of sudden death, both at the gross and
      microscopic levels, as well as toxicological examination. In this article, a
      brief discussion of those anatomic landmarks in the heart that may be related to
      the conduction system and the method of study of the conduction system is
      emphasized. An examination of the conduction system in 14 athletes revealed
      varying types of anomalies, both congenital and acquired in nature. The
      congenital abnormalities included abnormally developed sinoatrial (SA) and atrio
      ventricular (AV) nodes and AV bundle. The acquired changes included frequent
      association of mononuclear cell infiltration in the approaches to the SA node and
      the SA node, fat and fibrosis to a varying degree in all parts of the conduction
      system, and focal fibrotic scar areas in the ventricular septum. It is evident
      that these findings were present for a long period of time while the individual
      was totally asymptomatic. We therefore hypothesize that during an altered
      physiologic state, these congenital and/or acquired changes may form a milieu for
      an arrhythmic event to occur and/or promote an arrhythmic event in the vulnerable
      conduction system, which may in turn trigger varying types of reentry mechanisms,
      eventually leading to ventricular tachycardia, fibrillation, and sudden death. We
      also hypothesize that there may be a genetic and/or an autoimmune complex
      associated in some vulnerable conduction systems. 

PMID- 25990858
TI  - Extracardiac thrombotic, embolic, and hemorrhagic causes of sudden death.
AB  - The integrity of the vascular tree is essential to sustain life. However, blood
      vessels are the most vulnerable structure in the cardiovascular system, and
      disruption of the vasculature by occlusion (thrombosis/thromboembolism) or
      leakage (hemorrhage) can lead to sudden death. This review will concentrate on
      the extracardiac manifestations of two opposite, but intimately related,
      pathophysiologic processes that disturb vascular integrity: namely, thrombosis
      and hemorrhage. Thrombosis is a pathological process that leads to activation of
      the hemostatic system at an abnormal time and location. We are only just
      beginning to appreciate the myriad causes of thrombosis, some of which include
      vascular factors such as stasis and endothelial injury, as well as blood factors
      such as excessive coagulation, decreased coagulation inhibitors, or decreased
      fibrinolysis. Hemorrhage is a frequent cause of sudden death and may be
      attributable to blood vessel disease/rupture or to abnormalities within the blood
      itself that impair hemostasis. In this review, the pathophysiologic mechanisms of
      thrombosis/thromboembolism and hemorrhage are delineated and multiple system
      specific disease entities are discussed. 

PMID- 25990859
TI  - To the editor: The morphologic appearance of vasoseal(TM).

PMID- 25990860
TI  - Developing the Moti-4 intervention, assessing its feasibility and pilot testing
      its effectiveness.
AB  - BACKGROUND: The Moti-4 intervention was developed to prevent addiction and other
      health problems among vulnerable adolescent cannabis users. The aims of Moti-4
      are to reduce the use of cannabis among adolescents and to encourage their
      motivation to change their behavior. METHODS: Intervention Mapping, a systematic
      approach to developing theory- and evidence-based interventions, was used to
      develop a protocol for the intervention. The process of developing the
      intervention also used the method of responsive evaluation to explore the
      opinions of the immediate target group and intermediaries (N = 31). Feasibility
      was assessed in 9 interviews and analyzed in grids. A quantitative pilot analysis
      involving a pre- and post-assessment in 31 subjects assessed whether the
      intervention was able to reduce drug use and would change intentions to change
      drug use behavior. RESULTS: Using Intervention Mapping resulted in the
      development of a substantial four-session intervention with a clear manual and
      training for prevention workers. The choice of 12 consecutive steps was based on
      the Trans Theoretical Model of Behavior Change, Motivational Interviewing, Theory
      of Planned Behavior and the Self Determination Theory. Positive aspects of
      working with Moti-4 were assessed in a feasibility study. Criticism by users has
      led to improvements to the manual. In the pilot study, the average weekly amount
      spent on cannabis decreased significantly from an average ? 17.77 to ? 11,95 in
      the period after the intervention, with a medium effect size (d = 0.36).
      Likewise, a significant decrease was found in the frequency of use during the
      past week, from 4.3 to 2.4 (d = .52). As to motivation to change, a statistically
      significant increase was found in planning (d = .44) and a large increase in the
      desire to stop (d = .76). The change in the motivation to smoke less cannabis was
      small. CONCLUSION: Intervention Mapping proved to be a useful approach for the
      development of the intervention, using a productive combination of theory and
      community knowledge. The pre- and post-test pilot study showed that the
      intervention generally brought about a considerable positive change in the two
      principle targets, cannabis use and motivation. There is a need for further
      (controlled) research into its effectiveness and implementation as a standard
      method in addiction prevention services.

PMID- 25990861
TI  - Developing a fully integrated tobacco curriculum in medical colleges in India.
AB  - BACKGROUND: This paper describes a pioneering effort to introduce tobacco
      cessation into India's undergraduate medical college curriculum. This is the
      first ever attempt to fully integrate tobacco control across all years of medical
      college in any low and middle income country. The development, pretesting, and
      piloting of an innovative modular tobacco curriculum are discussed as well as
      challenges that face implementation and steps taken to address them and to
      advocate for adoption by the Medical Council of India. METHODS: In-depth
      interviews were conducted with administrators and faculty in five medical
      colleges to determine interest in and willingness to fully integrate smoking
      cessation into the college curriculum. Current curriculum was reviewed for
      present exposure to information about tobacco and cessation skill training. A
      modular tobacco curriculum was developed, pretested, modified, piloted, and
      evaluated by faculty and students. Qualitative research was conducted to identify
      challenges to future curriculum implementation. RESULTS: Fifteen modules were
      successfully developed focusing on the public health importance of tobacco
      control, the relationship between tobacco and specific organ systems, diseases
      related to smoking and chewing tobacco, and the impact of tobacco on medication
      effectiveness. Culturally sensitive illness specific cessation training videos
      were developed. Faculty and students positively evaluated the curriculum as
      increasing their competency to support cessation during illness as a teachable
      moment. Students conducted illness centered cessation interviews with patients as
      a mandated part of their coursework. Systemic challenges to implementing the
      curriculum were identified and addressed. CONCLUSIONS: A fully integrated tobacco
      curriculum for medical colleges was piloted in 5 colleges and is now freely
      available online. The curriculum has been adopted by the state of Kerala as a
      first step to gaining Medical Council of India review and possible recognition.

PMID- 25990862
TI  - Altered DNA methylation in PAH deficient phenylketonuria.
AB  - While phenylalanine (PHE) is the toxic insult in phenylketonuria (PKU),
      mechanisms underlying PHE toxicity remain ill-defined. Altered DNA methylation in
      response to toxic exposures is well-recognized. DNA methylation patterns were
      assessed in blood and brain from PKU patients to determine if PHE toxicity
      impacts methylation. Methylome assessment, utilizing methylated DNA
      immunoprecipitation and paired-end sequencing, was performed in DNA obtained from
      brain tissue of classical PKU patients, leukocytes from poorly controlled PKU
      patients, leukocytes from well controlled PKU patients, and appropriate control
      tissues. In PKU brain tissue, expression analysis determined the impact of
      methylation on gene function. Differential methylation was observed in brain
      tissue of PKU patients and expression studies identified downstream impact on
      gene expression. Altered patterns of methylation were observed in leukocytes of
      well controlled and poorly controlled patients with more extensive methylation in
      patients with high PHE exposure. Differential methylation of noncoding RNA genes
      was extensive in patients with high PHE exposure but minimal in well controlled
      patients. Methylome repatterning leading to altered gene expression was present
      in brain tissue of PKU patients, suggesting a role in neuropathology. Aberrant
      methylation is observed in leukocytes of PKU patients and is influenced by PHE
      exposure. DNA methylation may provide a biomarker relating to historic PHE
      exposure. 

PMID- 25990864
TI  - The effect of radiopacifiers agents on pH, calcium release, radiopacity, and
      antimicrobial properties of different calcium hydroxide dressings.
AB  - The aim of this study was to evaluate the antimicrobial activity, pH level,
      calcium ion release, and radiopacity of calcium hydroxide pastes associated with
      three radiopacifying agents (iodoform, zinc oxide, and barium sulfate). For the
      pH and calcium release tests, 45 acrylic teeth were utilized and immersed in
      ultrapure water. After 24 h, 72 h, and 7 days the solution was analyzed by using
      a pH meter and an atomic absorption spectrophotometer. Polyethylene tubes filled
      with the pastes were used to perform the radiopacity test. For the antimicrobial
      test, 25 dentin specimens were infected intraorally in order to induce the
      biofilm colonization and treated with the pastes for 7 days. The Live/Dead
      technique and a confocal microscope were used to obtain the ratio of live cells.
      Parametric and nonparametric statistical tests were performed to show differences
      among the groups (P < 0.05). The pH analysis at 7 days showed significant
      differences (P < 0.05) among the groups. No differences among the pastes were
      found in the calcium release test on the 7th day (P > 0.05). The calcium
      hydroxide/iodoform samples had the highest radiopacity and antimicrobial activity
      against the biofilm-infected dentin in comparison to the other pastes (P < 0.05).
      Calcium hydroxide mixed with 17% iodoform and 35% propylene glycol into a paste
      had the highest pH, calcium ion release, radiopacity, and the greatest
      antimicrobial action versus similar samples mixed with BaSO4 or ZnO.

PMID- 25990863
TI  - Transcription factor networks in B-cell differentiation link development to acute
      lymphoid leukemia.
AB  - B-lymphocyte development in the bone marrow is controlled by the coordinated
      action of transcription factors creating regulatory networks ensuring activation
      of the B-lymphoid program and silencing of alternative cell fates. This process
      is tightly connected to malignant transformation because B-lineage acute
      lymphoblastic leukemia cells display a pronounced block in differentiation
      resulting in the expansion of immature progenitor cells. Over the last few years,
      high-resolution analysis of genetic changes in leukemia has revealed that several
      key regulators of normal B-cell development, including IKZF1, TCF3, EBF1, and
      PAX5, are genetically altered in a large portion of the human B-lineage acute
      leukemias. This opens the possibility of directly linking the disrupted
      development as well as aberrant gene expression patterns in leukemic cells to
      molecular functions of defined transcription factors in normal cell
      differentiation. This review article focuses on the roles of transcription
      factors in early B-cell development and their involvement in the formation of
      human leukemia. 

PMID- 25990867
TI  - Association between diagnosed diabetes and trouble seeing, National Health
      Interview Survey, 2011-13.

PMID- 25990868
TI  - Determination of magnetic anisotropy in a multinuclear Tb(III)-based single
      molecule magnet.
AB  - Magneto-structural relationships were studied experimentally and theoretically
      for two enantiomorphic tetranuclear [CuTb]2 SMMs. For the first time, the
      determination of the magnetic anisotropy axis of an individual magnetic ion,
      Tb(3+), was achieved in a polynuclear Tb(3+)-based SMM. 

PMID- 25990865
TI  - Lower gray matter density and functional connectivity in the anterior insula in
      smokers compared with never smokers.
AB  - Although nicotine addiction is characterized by both structural and functional
      abnormalities in brain networks involved in salience and cognitive control, few
      studies have integrated these data to understand how these abnormalities may
      support addiction. This study aimed to (1) evaluate gray matter density and
      functional connectivity of the anterior insula in cigarette smokers and never
      smokers and (2) characterize how differences in these measures were related to
      smoking behavior. We compared structural magnetic resonance imaging (MRI) (gray
      matter density via voxel-based morphometry) and seed-based functional
      connectivity MRI data in 16 minimally deprived smokers and 16 matched never
      smokers. Compared with controls, smokers had lower gray matter density in left
      anterior insula extending into inferior frontal and temporal cortex. Gray matter
      density in this region was inversely correlated with cigarettes smoked per day.
      Smokers exhibited negative functional connectivity (anti-correlation) between the
      anterior insula and regions involved in cognitive control (left lPFC) and
      semantic processing/emotion regulation (lateral temporal cortex), whereas
      controls exhibited positive connectivity between these regions. There were
      differences in the anterior insula, a central region in the brain's salience
      network, when comparing both volumetric and functional connectivity data between
      cigarette smokers and never smokers. Volumetric data, but not the functional
      connectivity data, were also associated with an aspect of smoking behavior (daily
      cigarettes smoked).

PMID- 25990869
TI  - Cognitive flexibility differentiates young adults exhibiting obsessive-compulsive
      behaviors from controls.
AB  - The National Institute of Mental Health has proposed a shift toward classifying
      clusters of disorders on the basis of underlying biomarkers and neurological
      correlates. The present study sought to determine whether cognitive flexibility
      represents one such construct underlying obsessive-compulsive behaviors (OCBs), a
      cluster of behaviors characteristic of OCD and other body-focused repetitive
      behaviors (BFRBs), including trichotillomania, pathological skin picking, nail
      biting, and tic disorders. One-hundred and twenty-four undergraduate students
      completed the Depression Anxiety and Stress Scales, Padua Inventory-Washington
      State University Revision, Massachusetts General Hospital-Hairpulling Scale, Skin
      Picking Scale, and an Intradimensional/Extradimensional Shift (IDED) Test.
      Analyses were performed using a subsample of participants who met criteria for
      inclusion in the OCB group and a control group (N=56). Results indicated that
      young adults in the OCB group demonstrated significantly poorer performance on
      the IDED compared to controls. However, hierarchical regression analyses revealed
      that increased deficits in cognitive flexibility failed to predict worsened OCB
      severity-as assessed via a composite score. These results suggest that while
      cognitive flexibility differentiates those exhibiting OCBs from controls, it does
      not appear to be related to OCB severity. Future research is needed to replicate
      these results in larger clinical samples. 

PMID- 25990870
TI  - Optical pumping and readout of bismuth hyperfine states in silicon for atomic
      clock applications.
AB  - The push for a semiconductor-based quantum information technology has renewed
      interest in the spin states and optical transitions of shallow donors in silicon,
      including the donor bound exciton transitions in the near-infrared and the
      Rydberg, or hydrogenic, transitions in the mid-infrared. The deepest group V
      donor in silicon, bismuth, has a large zero-field ground state hyperfine
      splitting, comparable to that of rubidium, upon which the now-ubiquitous rubidium
      atomic clock time standard is based. Here we show that the ground state hyperfine
      populations of bismuth can be read out using the mid-infrared Rydberg
      transitions, analogous to the optical readout of the rubidium ground state
      populations upon which rubidium clock technology is based. We further use these
      transitions to demonstrate strong population pumping by resonant excitation of
      the bound exciton transitions, suggesting several possible approaches to a solid
      state atomic clock using bismuth in silicon, or eventually in enriched (28)Si. 

PMID- 25990871
TI  - [Evaluation of administration errors of injectable drugs in neonatology].
AB  - OBJECTIVE: Use of injectable drugs in newborns represents more than 90% of
      prescriptions and requires special precautions in order to ensure more safety and
      efficiency. The aim of this study is to gather errors relating to the
      administration of injectable drugs and to suggest corrective actions. METHODS:
      This descriptive and transversal study has evaluated 300 injectable drug
      administrations in a neonatology unit. Two hundred and sixty-one administrations
      have contained an error. Data are collected by direct observations of
      administrative act. RESULTS: Errors observed are: an inappropriate mixture (2.6%
      of cases); an incorrect delivery rate (33.7% of cases); incorrect dilutions
      (26.7% of cases); error in calculation of the dose to be injected (16.7% of
      cases); error while sampling small volumes (6.3% of cases); error or omission of
      administration schedule (1% of cases). CONCLUSION: These data have enabled us to
      evaluate administration of injectable drugs in neonatology. Different types of
      errors observed could be a source of therapeutic inefficiency, extended lengths
      of stay or iatrogenic drug. Following these observations, corrective actions have
      been undertaken by pharmacists and consist of: organizing training sessions for
      nursing; developing an explanatory guide for dilution and administration of
      injectable medicines, which was made available to the clinical service.
      Collaborative strategies doctor-nurse-pharmacist can help to reduce errors in the
      medication process especially during his administration. It permits improvement
      of injectable drugs use, offering more security and better efficiency and
      contribute to guarantee ideal therapy for patients.

PMID- 25990872
TI  - Phylogenetic Analysis and Functional Characterization of the Influenza A H5N1 PB2
      Gene.
AB  - Highly pathogenic avian influenza (HPAI) H5N1 viruses are endemic in poultry and
      cause continued inter-species transmission to human in Asia, such as China and
      Vietnam, leading to pandemic concerns and socio-economic challenges. Phylogenetic
      analysis of H5N1 viruses isolated from China and Vietnam during 2001-2012 showed
      that several geographically distinct sublineages have become established in these
      two countries. Subsequently, we reassigned HPAI H5N1 viruses into three distinct
      groups to reveal the intrasubtype reassortment. Apart from six reassortants
      detected here, we found that several viral strains showed signals for homologous
      recombination within PB2 and PB1 genes, suggestive of the fluidity of the H5N1
      virus gene pool. Furthermore, sequenced-based analyses revealed that the viral
      polymerase displayed a higher level of genetic polymorphism but associated with
      lower substitution rate when compared with those of other gene segments. In
      addition, the selection pressure analysis indicated that purifying selection was
      predominant in eight genomic segments especially in the polymerase complex.
      However, the site-by-site analysis helped to detect 14 positively selected sites
      in the PB1, PA, HA, NA, MP and NS proteins. Despite the fact that PB2 protein of
      H5N1 viruses was highly conserved at the amino acid level, eleven adaptive
      mutations were still observed in the protein. Further comparative structural
      analysis of the K627E mutation indicated that there were no structural
      differences between the variants, which possessed either PB2-627E or PB2-627K.
      Transcriptomic analysis suggested the non-mitochondrial PB2 protein of H5N1 virus
      that forms a stable complex with the mitochondrial antiviral signalling protein
      (MAVS, also known as IPS-1, VISA or Cardif) can induce interferon-beta (IFN-beta)
      expression, but the substitution (PB2-K627E) is not the sole determinant of the
      RIG-I-like receptors (RLR) signalling components induction in Calu-3 cells.

PMID- 25990873
TI  - 'Soft' amplifier circuits based on field-effect ionic transistors.
AB  - Soft materials can be used as the building blocks for electronic devices with
      extraordinary properties. We introduce a theoretical model for a field-effect
      transistor in which ions are the gated species instead of electrons. Our model
      incorporates readily-available soft materials, such as conductive porous
      membranes and polymer-electrolytes to represent a device that regulates ion
      currents and can be integrated as a component in larger circuits. By means of
      Nernst-Planck numerical simulations as well as an analytical description of the
      steady-state current we find that the responses of the system to various input
      voltages can be categorized into ohmic, sub-threshold, and active modes. This is
      fully analogous to what is known for the electronic field-effect transistor
      (FET). Pivotal FET properties such as the threshold voltage and the
      transconductance crucially depend on the half-cell redox potentials of the source
      and drain electrodes as well as on the polyelectrolyte charge density and the
      gate material work function. We confirm the analogy with the electronic FETs
      through numerical simulations of elementary amplifier circuits in which we
      successfully substitute the electronic transistor by an ionic transistor. 

PMID- 25990874
TI  - Hyper-IgD syndrome/mevalonate kinase deficiency: what is new?
AB  - Mevalonate kinase deficiency or hyper-IgD syndrome is a hereditary
      autoinflammatory syndrome caused by mutations in the mevalonate kinase gene. In
      this review, we will discuss new findings in this disorder that have been
      published in the last 2 years. This includes new insights into pathophysiology,
      treatment, and the clinical phenotype linked to the genetic defect. 

PMID- 25990875
TI  - Resource specialisation and the divergence of killer whale populations.

PMID- 25990876
TI  - Mapping and validation of a major QTL affecting resistance to pancreas disease
      (salmonid alphavirus) in Atlantic salmon (Salmo salar).
AB  - Pancreas disease (PD), caused by a salmonid alphavirus (SAV), has a large
      negative economic and animal welfare impact on Atlantic salmon aquaculture.
      Evidence for genetic variation in host resistance to this disease has been
      reported, suggesting that selective breeding may potentially form an important
      component of disease control. The aim of this study was to explore the genetic
      architecture of resistance to PD, using survival data collected from two
      unrelated populations of Atlantic salmon; one challenged with SAV as fry in
      freshwater (POP 1) and one challenged with SAV as post-smolts in sea water (POP
      2). Analyses of the binary survival data revealed a moderate-to-high heritability
      for host resistance to PD in both populations (fry POP 1 h(2)~0.5; post-smolt POP
      2 h(2)~0.4). Subsets of both populations were genotyped for single nucleotide
      polymorphism markers, and six putative resistance quantitative trait loci (QTL)
      were identified. One of these QTL was mapped to the same location on chromosome 3
      in both populations, reaching chromosome-wide significance in both the sire- and
      dam-based analyses in POP 1, and genome-wide significance in a combined analysis
      in POP 2. This independently verified QTL explains a significant proportion of
      host genetic variation in resistance to PD in both populations, suggesting a
      common underlying mechanism for genetic resistance across lifecycle stages.
      Markers associated with this QTL are being incorporated into selective breeding
      programs to improve PD resistance.

PMID- 25990877
TI  - p53 gene discriminates two ecologically divergent sister species of pine voles.
AB  - Genes with relevant roles in the differentiation of closely-related species are
      likely to have diverged simultaneously with the species and more accurately
      reproduce the species tree. The Lusitanian (Microtus lusitanicus) and
      Mediterranean (M. duodecimcostatus) pine voles are two recently separated sister
      species with fossorial lifestyles whose different ecological, physiological and
      morphological phenotypes reflect the better adaptation of M. duodecimcostatus to
      the underground habitat. Here we asked whether the differentiation of M.
      lusitanicus and M. duodecimcostatus involved genetic variations within the tumour
      suppressor p53 gene, given its role in stress-associated responses. We performed
      a population-genetic analysis through sequencing of exons and introns of p53 in
      individuals from sympatric and allopatric populations of both the species in the
      Iberian Peninsula in which a unidirectional introgression of mitochondrial DNA
      was previously observed. We were able to discriminate the two species to a large
      extent. We show that M. duodecimcostatus is composed of one genetically
      unstructured group of populations sharing a P53 protein that carries a mutation
      in the DNA-binding region not observed in M. lusitanicus, raising the possibility
      that this mutation may have been central in the evolutionary history of M.
      duodecimcostatus. Our results provide suggestive evidence for the involvement of
      a master transcription factor in the separation of M. lusitanicus and M.
      duodecimcostatus during Microtus radiation in the Quaternary presumably via a
      differential adaptive role of the novel p53 in M. duodecimcostatus. 

PMID- 25990878
TI  - Properties of different selection signature statistics and a new strategy for
      combining them.
AB  - Identifying signatures of recent or ongoing selection is of high relevance in
      livestock population genomics. From a statistical perspective, determining a
      proper testing procedure and combining various test statistics is challenging. On
      the basis of extensive simulations in this study, we discuss the statistical
      properties of eight different established selection signature statistics. In the
      considered scenario, we show that a reasonable power to detect selection
      signatures is achieved with high marker density (>1 SNP/kb) as obtained from
      sequencing, while rather small sample sizes (~15 diploid individuals) appear to
      be sufficient. Most selection signature statistics such as composite likelihood
      ratio and cross population extended haplotype homozogysity have the highest power
      when fixation of the selected allele is reached, while integrated haplotype score
      has the highest power when selection is ongoing. We suggest a novel strategy,
      called de-correlated composite of multiple signals (DCMS) to combine different
      statistics for detecting selection signatures while accounting for the
      correlation between the different selection signature statistics. When examined
      with simulated data, DCMS consistently has a higher power than most of the single
      statistics and shows a reliable positional resolution. We illustrate the new
      statistic to the established selective sweep around the lactase gene in human
      HapMap data providing further evidence of the reliability of this new statistic.
      Then, we apply it to scan selection signatures in two chicken samples with
      diverse skin color. Our analysis suggests that a set of well-known genes such as
      BCO2, MC1R, ASIP and TYR were involved in the divergent selection for this trait.

PMID- 25990880
TI  - Extent of distal resection for bicuspid aortopathy: Is surgical experience a
      factor?

PMID- 25990879
TI  - Long telomeres are associated with clonality in wild populations of the
      fissiparous starfish Coscinasterias tenuispina.
AB  - Telomeres usually shorten during an organism's lifespan and have thus been used
      as an aging and health marker. When telomeres become sufficiently short,
      senescence is induced. The most common method of restoring telomere length is via
      telomerase reverse transcriptase activity, highly expressed during embryogenesis.
      However, although asexual reproduction from adult tissues has an important role
      in the life cycles of certain species, its effect on the aging and fitness of
      wild populations, as well as its implications for the long-term survival of
      populations with limited genetic variation, is largely unknown. Here we compare
      relative telomere length of 58 individuals from four populations of the asexually
      reproducing starfish Coscinasterias tenuispina. Additionally, 12 individuals were
      used to compare telomere lengths in regenerating and non-regenerating arms, in
      two different tissues (tube feet and pyloric cecum). The level of clonality was
      assessed by genotyping the populations based on 12 specific microsatellite loci
      and relative telomere length was measured via quantitative PCR. The results
      revealed significantly longer telomeres in Mediterranean populations than
      Atlantic ones as demonstrated by the Kruskal-Wallis test (K=24.17, significant
      value: P-value<0.001), with the former also characterized by higher levels of
      clonality derived from asexual reproduction. Telomeres were furthermore
      significantly longer in regenerating arms than in non-regenerating arms within
      individuals (pyloric cecum tissue: Mann-Whitney test, V=299, P-value<10(-6); and
      tube feet tissue Student's t=2.28, P-value=0.029). Our study suggests that one of
      the mechanisms responsible for the long-term somatic maintenance and persistence
      of clonal populations is telomere elongation. 

PMID- 25990881
TI  - Seeing cancer in a new light.

PMID- 25990882
TI  - Quantifying regional left ventricular contractile function: Leave it to the
      machines?

PMID- 25990883
TI  - Within-subject haemoglobin variation in elite athletes: a longitudinal
      investigation of 13 887 haemoglobin concentration readings.
AB  - The Athlete Biological Passport (ABP) estimates individualized reference ranges
      for key blood markers, such as haemoglobin concentration ([Hb]), using
      predetermined population mean, between- and within-subject variances. Here, we
      aim to reassess previously published estimates for within-subject [Hb] variance
      and determine whether sex-, analyzer-, sport-, or season-specific values are
      required. Our reference population contains 7723 male (mean +/- SD, 22.3 +/- 4.6
      years of age) and 6164 female (21.6 +/- 4.3) athlete observations from 49 sports.
      [Hb] was calculated using one of three cytometers; Bayer-H3 (1997-1999, n =
      4554), ADVIA-120 (1999-2010, n = 8636) and Sysmex XT-2000i (2010-2012, n = 697).
      The final model was a linear mixed model for [Hb] with analyzer (H3, ADVIA,
      Sysmex), sex (male, female), sport (power-endurance, endurance, skill, team,
      disabled and non-athletes), season (summer, winter), and the interaction between
      sex and sport as fixed effects and athlete as a random effect. The model included
      an exponential correlation structure to allow for within-subject autocorrelation,
      and allowed different within-subject variances for each sport. Within-subject
      [Hb] variance (g(2) /L(2) ) was significantly less for power endurance (35.09,
      95% CI 33.50 to 36.76), disabled (25.82, 95% CI 21.71 to 35.28) and non-athletes
      (34.30, 95% CI 28.53 to 35.87) than for endurance (40.35, 95% CI 39.62 to 47.22)
      and team sports (38.70, 95% CI 37.68 to 39.76) athletes. No new evidence was
      found to justify adjusting the current within-subject [Hb] variance estimate.

PMID- 25990884
TI  - Iterative image reconstruction that includes a total variation regularization for
      radial MRI.
AB  - This paper presents an iterative image reconstruction method for radial encodings
      in MRI based on a total variation (TV) regularization. The algebraic
      reconstruction method combined with total variation regularization (ART_TV) is
      implemented with a regularization parameter specifying the weight of the TV term
      in the optimization process. We used numerical simulations of a Shepp-Logan
      phantom, as well as experimental imaging of a phantom that included a rectangular
      wave chart, to evaluate the performance of ART_TV, and to compare it with that of
      the Fourier transform (FT) method. The trade-off between spatial resolution and
      signal-to-noise ratio (SNR) was investigated for different values of the
      regularization parameter by experiments on a phantom and a commercially available
      MRI system. ART_TV was inferior to the FT with respect to the evaluation of the
      modulation transfer function (MTF), especially at high frequencies; however, it
      outperformed the FT with regard to the SNR. In accordance with the results of SNR
      measurement, visual impression suggested that the image quality of ART_TV was
      better than that of the FT for reconstruction of a noisy image of a kiwi fruit.
      In conclusion, ART_TV provides radial MRI with improved image quality for low-SNR
      data; however, the regularization parameter in ART_TV is a critical factor for
      obtaining improvement over the FT. 

PMID- 25990885
TI  - Adenovirus in Rural Cote D'Ivoire: High Diversity and Cross-Species Detection.
AB  - The Tai region in Western Cote d'Ivoire is characterized by extensive overlap of
      human and animal habitats. This could influence patterns of adenovirus
      transmission between humans and domestic animals. Fecal samples from humans and
      various domestic animals were tested for the presence of adenoviruses by PCR.
      Phylogenetic and species delineation analyses were performed to further
      characterize the adenoviruses circulating in the region and to identify potential
      cross-species transmission events. Among domestic animals, adenovirus shedding
      was frequent (21.6% of domestic mammals and 41.5% of chickens) and the detected
      strains were highly diverse, several of them representing novel types. Although
      no evidence for zoonotic transmission of animal adenovirus was obtained, the
      present study provides concordant evidence in favor of common cross-species
      transmission of adenoviruses between different animal species and first
      indications for adenovirus transmission from humans to animals. These findings
      underline the thus far underestimated importance of reverse zoonotic transmission
      of viruses and of the role of domestic animals as pathogen reservoirs, "bridge
      species," or intermediate hosts.

PMID- 25990886
TI  - Impact of monoamine-related gene polymorphisms on hippocampal volume in treatment
      resistant depression.
AB  - OBJECTIVE: In major depressive disorder (MDD), single nucleotide polymorphisms
      (SNPs) in monoaminergic genes may impact disease susceptibility, treatment
      response, and brain volume. The objective of this study was to examine the effect
      of such polymorphisms on hippocampal volume in patients with treatment-resistant
      MDD and healthy controls. Candidate gene risk alleles were hypothesised to be
      associated with reductions in hippocampal volume. METHODS: A total of 26
      outpatients with treatment-resistant MDD and 27 matched healthy controls
      underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic
      genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2),
      serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase
      (COMT), and brain-derived neurotrophic factor (BDNF)]. Hippocampal volume was
      estimated using an automated segmentation algorithm (FreeSurfer). RESULTS:
      Hippocampal volume did not differ between patients and controls. Within the
      entire study sample irrespective of diagnosis, C allele-carriers for both the NET
      182 T/C [rs2242446] and 5-HT1A-1019C/G [rs6295] polymorphisms had smaller
      hippocampal volumes relative to other genotypes. For the 5-HTTLPR (rs25531)
      polymorphism, there was a significant diagnosis by genotype interaction effect on
      hippocampal volume. Among patients only, homozygosity for the 5-HTTLPR short (S)
      allele was associated with smaller hippocampal volume. There was no association
      between the 5-HT2A, COMT, and BDNF SNPs and hippocampal volume. CONCLUSION: The
      results indicate that the volume of the hippocampus may be influenced by
      serotonin- and norepinephrine-related gene polymorphisms. The NET and 5-HT1A
      polymorphisms appear to have similar effects on hippocampal volume in patients
      and controls while the 5-HTTLPR polymorphism differentially affects hippocampal
      volume in the presence of depression.

PMID- 25990887
TI  - Effect of faecal soiling on skatole and androstenone occurrence in organic entire
      male pigs.
AB  - Production of entire male pigs could be a future strategy for organic pig
      production. However, production of entire males leads to increased risk of
      carcasses with elevated boar taint levels. It is hypothesized that skatole levels
      in pig meat are affected by faecal soiling and that organic housing facilities
      can increase the risk of pigs being heavily soiled. Therefore, the overall aim of
      this study was to investigate if increased pig and pen soiling increases skatole
      concentration in entire male pigs. In five herds, 1174 organic entire male pigs
      were reared in four batches across two seasons, summer and winter. Measurements
      of pig and pen soiling, as well as fat skatole and androstenone concentration and
      human nose sensory tests of fat odour, were performed. Skatole and androstenone
      concentrations varied greatly within and between herds with a 10% and 90%
      percentile for the overall population of 0.02 and 2.25 ug/g for skatole and 0.53
      and 4.84 ug/g for androstenone. Human nose positive tests averaged 18.3% with
      great variation between herds and seasons. Pen soiling had significant effects on
      pig soiling. Moreover, outdoor pen soiling significantly affected skatole
      concentration in interactions with herd and season (P<0.001 and P=0.003) and
      affected human nose positive risk in interaction with herd (P=0.005). Soiling on
      indoor pen areas did not affect skatole levels and no effect on androstenone was
      found for any pen area. Soiling of pigs affected both skatole and androstenone
      levels, with the size of the head and abdomen body areas covered in manure
      showing significant positive effects on skatole concentration. No effect of
      density of the manure layer was found on either boar taint measure. Herd
      significantly affected both skatole and androstenone in fat as well as the human
      nose positive risk. The human nose test revealed no effect from pig soiling. A
      large variation in the different boar taint measures was found for both high and
      low scores of pen and pig soiling, and only a small difference in skatole and
      androstenone concentrations between the high and low soiling categories was
      found. Therefore, while increasing the hygiene management could be a strategy for
      reducing boar taint in production of organic entire male pigs, it should be
      emphasized that other factors would also need to be considered.

PMID- 25990889
TI  - Using administrative discharge diagnoses to track hospital-acquired pressure
      ulcer incidence--limitations, links, and leaps.

PMID- 25990890
TI  - Comparative effectiveness of quality improvement interventions for pressure ulcer
      prevention in academic medical centers in the United States.
AB  - BACKGROUND: Prevention of pressure ulcers, one of the hospital-acquired
      conditions (HACs) targeted by the 2008 nonpayment policy of the Centers for
      Medicare & Medicaid Services (CMS), is a critical issue. This study was conducted
      to determine the comparative effectiveness of quality improvement (QI)
      interventions associated with reduced hospital-acquired pressure ulcer (HAPU)
      rates. METHODS: In an quasi-experimental design, interrupted time series analyses
      were conducted to determine the correlation between HAPU incidence rates and
      adoption of QI interventions. Among University HealthSystem Consortium hospitals,
      55 academic medical centers were surveyed from September 2007 through February
      2012 for adoption patterns of QI interventions for pressure ulcer prevention, and
      hospital-level data for 5,208 pressure ulcer cases were analyzed. Between- and
      within-hospital reduction significance was tested with t-tests post-CMS policy
      intervention. RESULTS: Fifty-three (96%) of the 55 hospitals used QI
      interventions for pressure ulcer prevention. The effect size analysis identified
      five effective interventions that each reduced pressure ulcer rates by greater
      than 1 case per 1,000 patient discharges per quarter: leadership initiatives,
      visual tools, pressure ulcer staging, skin care, and patient nutrition. The
      greatest reductions in rates occurred earlier in the adoption process (p<.05).
      CONCLUSIONS: Five QI interventions had clinically meaningful associations with
      reduced stage III and IV HAPU incidence rates in 55 academic medical centers.
      These QI interventions can be used in support of an evidence-based prevention
      protocol for pressure ulcers. Hospitals can not only use these findings from this
      study as part of a QI bundle for preventing HAPUs.

PMID- 25990891
TI  - Hospital-Acquired Pressure Ulcers at Academic Medical Centers in the United
      States, 2008-2012: Tracking Changes Since the CMS Nonpayment Policy.
AB  - BACKGROUND: In 2007, the Centers for Medicare & Medicaid Services (CMS) announced
      its intention to no longer reimburse hospitals for costs associated with hospital
      acquired pressure ulcers (HAPUs) and a list of other hospital-acquired conditions
      (HACs), which was followed by enactment of the nonpayment policy in October 2008.
      This study was conducted to define changes in HAPU incidence and variance since
      2008. METHODS: In a retrospective observational study, HAPU cases were identified
      at 210 University HealthSystem Consortium (UHC) academic medical centers in the
      United States. HAPU incidence rates were calculated as a ratio of HAPU cases to
      the total number of UHC inpatients between the first quarter of 2008 and the
      second quarter of 2012. HAPU cases were defined by multiple criteria: not present
      on admission (POA); coded for stage III or IV pressure ulcers; and a length of
      stay greater than four days. RESULTS: Among the UHC hospitals between 2008 and
      June 2012, 10,386 HAPU cases were identified among 4.08 million inpatients. The
      HAPU incidence rate decreased significantly from 11.8 cases per 1,000 inpatients
      in 2008 to 0.8 cases per 1,000 in 2012 (p < .001; 95% confidence interval: 8.39
      8.56). Among HAPU cases were trends of more elderly patients, greater case-mix
      index, and more surgical cases. The analysis of covariance model identified CMS
      non-payment policy as a significant covariate of changing trends in HAPU
      incidence rates. CONCLUSIONS: HAPU incidence rates decreased significantly among
      210 UHC AMCs after the enactment of the CMS nonpayment policy. The hospitals
      appeared to be reacting efficiently to economic policy incentives by improving
      prevention efforts.

PMID- 25990892
TI  - Using the integrated nurse leadership program to reduce sepsis mortality.
AB  - BACKGROUND: The Integrated Nurse Leadership Program (INLP) is a collaborative
      improvement model focused on developing practical leadership skills of nurses and
      other frontline clinicians to lead quality improvement efforts. Sepsis is a major
      challenge to treat because it arises unpredictably and can progress rapidly. Nine
      San Francisco Bay Area hospitals participated in a 22-month INLP Sepsis Mortality
      Reduction Project to improve sepsis detection and management. METHODS: The INLP
      focused on developing leadership and process improvement skills of nurses and
      other frontline clinicians. Teams of trained clinicians then implemented three
      strategies to improve early identification and timely treatment of sepsis: (1)
      sepsis screening of all patients, with diagnostic testing according to protocol;
      (2) timely treatment on the basis of key elements of Early Goal-Directed Therapy
      (EGDT); and (3) ongoing data review. Each hospital agreed to pursue the goal of
      reducing sepsis mortality by 15% by the end of the project. RESULTS: In the data
      collection period (baseline, July-December 2008 and project completion, January
      June 2011), team members showed strong improvement in perceived leadership
      skills, team effectiveness, and ability to improve care quality. During this
      period, sepsis mortality for eight of the participating hospitals (Hospital 9
      joined the project six months after it began) decreased by 43.7%-from 28% in the
      baseline period to 16% at project completion. Sepsis mortality rates trended
      downward for all hospitals, significantly decreasing (p<.05 at one hospital,
      p<.01 for four hospitals). CONCLUSIONS: In addition to improvement in safety
      culture and management of septic patients, hospitals participating in the INLP
      Sepsis Mortality Reduction Project achieved reductions in sepsis mortality during
      the study period and sustained reductions for more than one year later. The INLP
      model can be readily applied beyond sepsis management and mortality to other
      quality problems.

PMID- 25990893
TI  - Patient-collected audio for performance assessment of the clinical encounter.

PMID- 25990894
TI  - "Never events" and the quest to reduce preventable harm.

PMID- 25990895
TI  - Preparation and evaluation of monodispersed, submicron, non-porous silica
      particles functionalized with beta-CD derivatives for chiral-pressurized
      capillary electrochromatography.
AB  - Submicron, non-porous, chiral silica stationary phase has been prepared by the
      immobilization of functionalized beta-CD derivatives to isocyanate-modified
      silica via chemical reaction and applied to the pressurized capillary
      electrochromatography (pCEC) enantio-separation of various chiral compounds. The
      submicron, non-porous, cyclodextrin-based chiral stationary phases (sub_MUm-CSP2)
      exhibited excellent chiral recognition of a wide range of analytes including
      clenbuterol hydrochloride, mexiletine hydrochloride, chlorpheniramine maleate,
      esmolol hydrochloride, and metoprolol tartrate. The synthesized submicron
      particles were regularly spherical and uniformly non-porous with an average
      diameter of around 800 nm and a mean pore size of less than 2 nm. The synthesized
      chiral stationary phase was packed into 10 cm * 100 MUm id capillary columns. The
      sub_MUm-CSP2 column used in the pCEC system showed better separation of the
      racemates and at a higher rate compared to those used in the capillary liquid
      chromatography mode (cLC) system. The sub_MUm-CSP2 possessed high mechanical
      strength, high stereoselectivity, and long lifespan, demonstrating rapid enantio
      separation and good resolution of samples. The column provided an efficiency of
      up to 170,000 plates/m for n-propylbenzene.

PMID- 25990897
TI  - Automatic negation detection in narrative pathology reports.
AB  - OBJECTIVE: To detect negations of medical entities in free-text pathology reports
      with different approaches, and evaluate their performances. METHODS AND MATERIAL:
      Three different approaches were applied for negation detection: the lexicon-based
      approach was a rule-based method, relying on trigger terms and termination clues;
      the syntax-based approach was also a rule-based method, where the rules and
      negation patterns were designed using the dependency output from the Stanford
      parser; the machine-learning-based approach used a support vector machine as a
      classifier to build models with a number of features. A total of 284 English
      pathology reports of lymphoma were used for the study. RESULTS: The machine
      learning-based approach had the best overall performance on the test set with
      micro-averaged F-score of 82.56%, while the syntax-based approach performed worst
      with 78.62% F-score. The lexicon-based approach attained an overall average
      precision of 89.74% and recall of 76.09%, which were significantly better than
      the results achieved by Negation Tagger with a similar approach. DISCUSSION: The
      lexicon-based approach benefitted from being customized to the corpus more than
      the other two methods. The errors in negation detection with the syntax-based
      approach producing poorest performance were mainly due to the poor parsing
      results, and the errors with the other methods were probably because of the
      abnormal grammatical structures. CONCLUSIONS: A machine-learning-based approach
      has potential advantages for negation detection, and may be preferable for the
      task. To improve the overall performance, one of the possible solutions is to
      apply different approaches to each section in the reports.

PMID- 25990896
TI  - Increased gene dosage of Ink4/Arf and p53 delays age-associated central nervous
      system functional decline.
AB  - The impairment of the activity of the brain is a major feature of aging, which
      coincides with a decrease in the function of neural stem cells. We have
      previously shown that an extra copy of regulated Ink4/Arf and p53 activity, in s
      Ink4/Arf/p53 mice, elongates lifespan and delays aging. In this work, we examined
      the physiology of the s-Ink4/Arf/p53 brain with aging, focusing on the neural
      stem cell (NSC) population. We show that cells derived from old s-Ink4/Arf/p53
      mice display enhanced neurosphere formation and self-renewal activity compared
      with wt controls. This correlates with augmented expression of Sox2, Sox9, Glast,
      Ascl1, and Ars2 NSC markers in the subventricular zone (SVZ) and in the
      subgranular zone of the dentate gyrus (DG) niches. Furthermore, aged s
      Ink4/Arf/p53 mice express higher levels of Doublecortin and PSA-NCAM
      (neuroblasts) and NeuN (neurons) in the olfactory bulbs (OB) and DG, indicating
      increased neurogenesis in vivo. Finally, aged s-Ink4/Arf/p53 mice present
      enhanced behavioral and neuromuscular coordination activity. Together, these
      findings demonstrate that increased but regulated Ink4/Arf and p53 activity
      ameliorates age-related deterioration of the central nervous system activity
      required to maintain the stem cell pool, providing a mechanism not only for the
      extended lifespan but also for the health span of these mice.

PMID- 25990898
TI  - Crystallizing glassy issues.

PMID- 25990899
TI  - New horizons for glass formation and stability.

PMID- 25990900
TI  - Tuning order in disorder.

PMID- 25990901
TI  - Is metallic glass poised to come of age?

PMID- 25990907
TI  - Organic-inorganic perovskites: Lower threshold for nanowire lasers.

PMID- 25990908
TI  - Superconducting qubits: Solving a wonderful problem.

PMID- 25990909
TI  - Material witness: Pushing nanotubes to the limit.

PMID- 25990910
TI  - 2D semiconductors: One at a time.

PMID- 25990911
TI  - Superconductivity: The persistence of pairs.

PMID- 25990912
TI  - Photochemical transformations on plasmonic metal nanoparticles.
AB  - The strong interaction of electromagnetic fields with plasmonic nanomaterials
      offers opportunities in various technologies that take advantage of photophysical
      processes amplified by this light-matter interaction. Recently, it has been shown
      that in addition to photophysical processes, optically excited plasmonic
      nanoparticles can also activate chemical transformations directly on their
      surfaces. This potentially offers a number of opportunities in the field of
      selective chemical synthesis. In this Review we summarize recent progress in the
      field of photochemical catalysis on plasmonic metallic nanostructures. We discuss
      the underlying physical mechanisms responsible for the observed chemical
      activity, and the issues that must be better understood to see progress in the
      field of plasmon-mediated photocatalysis. 

PMID- 25990913
TI  - Molecular design and synthesis of a pH independent and cell permeant fluorescent
      dye and its applications.
AB  - Fluorescent dyes have played crucial roles in the field of molecular imaging as
      fluorescent fluorophores. In this work, a novel water-soluble and pH-independent
      fluorescent xanthene dye, a hydroxyl regioisomeric 3',4'-benzorhodol, has been
      designed and synthesized. Compared with those of rhodol dyes, the absorption (ca.
      570 nm) and maximum emission (ca. 620 nm) of the dye are largely red-shifted. Due
      to its ring-opened zwitterion structure in water media, the dye showed good
      membrane permeability and distributed in the whole cell cytoplasm upon incubation
      with live cells. Meanwhile, the dye could be easily modified to probes. The
      hydrazide derivative of the dye exhibited an excellent Hg(2+) selectivity over
      other relevant metal ions with a detection limit down to 3 nM. Thus, the
      excellent fluorescence properties and chemical properties of the dye allow it to
      be designed as a fluorescent chemosensor and biomarker for biological
      applications. 

PMID- 25990914
TI  - High Vertical Resolution Full-Field Reflection-Type Three-Dimensional Angle
      Deviation Microscope with Nonlinear Error Compensation.
AB  - This study examines the use of reflectivity-height transformation in full-field
      angle-deviation microscopes (ADM). In such microscopes, two light intensity
      distribution images of a prism's total internal reflection and critical angle are
      obtained separately with two charge-coupled devices (CCDs), and are converted
      into a reflectivity profile point-to-point and then into angle of deviation
      matrix after the beam is reflected by the test sample; finally, the surface
      height of the sample is found through the triangular geometrical relationship.
      This method obtains the image through the effective imaging area of CCD. Once the
      two-dimensional (2D) image is obtained, the third dimension, height, is added to
      create a full-field 3D surface profile. Its conversion process is nonlinear;
      therefore, compensation must be made to reduce measurement errors. The optical
      magnification of high vertical resolution full-field 3D reflection-type ADM could
      reach >250 times, thus providing submicron measurements with nanometer vertical
      resolution and allowing for the simultaneous measurement of 2D and 3D images.
      Small defects on both transparent and nontransparent surfaces can be rapidly
      detected. 

PMID- 25990915
TI  - Favourable effects of grape seed extract on intestinal epithelial differentiation
      and barrier function in IL10-deficient mice.
AB  - The impairment in the rate of cell proliferation and differentiation leads to a
      negative consequence on the renewal of the intestinal epithelium, which is the
      aetiological factor of a number of digestive diseases. Grape seed extract (GSE),
      a rich source of proanthocyanidins, is known for its beneficial health effects.
      The present study evaluated the beneficial effects of GSE on colonic cell
      differentiation and barrier function in IL10-deficient mice. Female mice aged 6
      weeks were randomised into two groups and given drinking-water containing 0 or
      0.1 % GSE (w/v) for 12 weeks. GSE supplementation decreased serum TNF-alpha level
      and intestinal permeability, and increased the colonic goblet cell density that
      was associated with increased mRNA expression of mucin (Muc)-2.
      Immunohistochemical analyses showed lower accumulation of beta-catenin in the
      crypts of colon tissues of the GSE-supplemented mice, which was associated with a
      decreased mRNA expression of two downstream effectors of Wingless and Int
      (Wnt)/catenin signalling, myelocytomatosis oncogene protein (Myc) and cyclin D1
      (Ccnd1). Consistently, GSE supplementation decreased the number of colonic
      proliferating cell nuclear antigen-positive cells, a well-known cell
      proliferation marker, and a weakened extracellular signal-regulated kinases 1 and
      2 (ERK1/2) signalling. In summary, these data indicate that supplementation of
      0.1 % GSE for 12 weeks improved gut barrier function and colonic cell
      differentiation in the IL10-deficient mice probably via inhibiting Wnt/beta
      catenin pathway.

PMID- 25990916
TI  - Types and Number of Traumas Associated With Suicidal Ideation and Suicide
      Attempts in PTSD: Findings From a U.S. Nationally Representative Sample.
AB  - Posttraumatic stress disorder (PTSD) is associated with suicidal ideation and
      suicide attempt; however, research has largely focused on specific samples and a
      limited range of traumas. We examined suicidal ideation and suicide attempt
      relating to 27 traumas within a nationally representative U.S. sample of
      individuals with PTSD. Data were from the National Epidemiologic Survey of
      Alcohol and Related Conditions (N = 34,653). Participants were assessed for
      lifetime PTSD and trauma history, suicidal ideation, and suicide attempt. We
      calculated the proportion of individuals reporting suicidal ideation or suicide
      attempt for each trauma and for the number of unique traumas experienced. Most
      traumas were associated with greater suicidal ideation and suicide attempt in
      individuals with PTSD compared to individuals with no lifetime trauma or with
      lifetime trauma but no PTSD. Childhood maltreatment, assaultive violence, and
      peacekeeping traumas had the highest rates of suicidal ideation (49.1% to 51.9%)
      and suicide attempt (22.8% to 36.9%). There was substantial variation in rates of
      suicidal ideation and suicide attempt for war and terrorism-related traumas.
      Multiple traumas increased suicidality, such that each additional trauma was
      associated with an increase of 20.1% in rate of suicidal ideation and 38.9% in
      rate of suicide attempts. Rates of suicidal ideation and suicide attempts varied
      markedly by trauma type and number of traumas, and these factors may be important
      in assessing and managing suicidality in individuals with PTSD. 

PMID- 25990917
TI  - Evaluation of the effectiveness of uvulopalatopharyngoplasty. 1985.

PMID- 25990919
TI  - Using Health Information Technology to Support Evidence-Based Practice.

PMID- 25990918
TI  - Relationships among Puberty, Muscle and Fat, and Liveweight Gain during Mating in
      Young Female Sheep.
AB  - Greater depths of muscle are associated with better reproductive performance in
      ewe lambs, but, in adult ewes, reproductive performance also seems to vary with
      liveweight gain during the mating period. Therefore, in a large field study with
      Merino ewe lambs, we tested whether the relationships among eye muscle depth
      (EMD), fat depth (FAT) and reproductive performance depend on liveweight gain
      during the mating period. We selected lambs with a wide range in phenotypic
      values for depths of eye muscle (EMD) and fat (FAT) and assigned them to dietary
      treatments designed to achieve low (LOW, n = 244) or high (HIGH, n = 237) rates
      of liveweight gain during a 28-day mating period. The LOW treatment maintained
      live weight, whereas the HIGH treatment gained 179 +/- 3.8 g/day (p < 0.001).
      From those ewe lambs that attained puberty, first oestrus was detected at live
      weight 37.8 +/- 0.2 kg and age 232 days. The proportion of ewes that attained
      puberty increased with EMD (p < 0.01). Ewes from the HIGH treatment were more
      fertile (pregnant ewes per 100 ewes exposed to rams) and had a higher
      reproductive rate (foetuses in utero per 100 ewes exposed to rams; p < 0.001)
      than those from the LOW treatment. Fertility and reproductive rate were
      positively correlated with weight gain during mating as well as live weight at
      the start of mating, FAT and EMD (p < 0.05 to <0.001). We conclude that faster
      growth, due to either extra nutrition during mating or higher phenotypic
      potential for fat and muscle, will increase reproductive performance in ewe lambs
      mated at 8 months of age. 

PMID- 25990921
TI  - Core-Shell Collagen Peptide Chelated Calcium/Calcium Alginate Nanoparticles from
      Fish Scales for Calcium Supplementation.
AB  - We report simple methods for preparing collagen peptide chelated calcium (cpcc)
      and a novel cpcc-loaded nanoparticle from marine fish scales for calcium
      supplementation. Cpcc nanoparticles have an average diameter of approximately 150
      nm and a calcium content of up to 130.4 g/kg. Calcium alginate was selected to
      encapsulate cpcc for the preparation of core-shell cpcc/calcium alginate
      nanoparticles. The core-shell nanoparticles were mainly 200 to 500 nm in
      diameter. The ratio of calcium to sulfur was approximately 1.6:1. In vivo
      experiments indicated both cpcc and core-shell cpcc were able to improve calcium
      absorption and prevent calcium deficiency. Especially core-shell cpcc worked well
      to increase femur bone mineral density and femur calcium content in rats
      significantly. The study demonstrated that cpcc and core-shell cpcc nanoparticles
      were ideal for calcium supplementation. PRACTICAL APPLICATION: Calcium deficiency
      has become an increasingly relevant health concern in the food industry. There is
      an urgent need for new effective calcium supplements. This study consisted of
      preparing and characterizing alginate nanoparticles loaded with collagen peptide
      chelated calcium. These nanoparticles can enhance calcium absorption
      significantly and prevent calcium deficiency. The data presented in this study
      can aid the food industry in developing a new ideal calcium supplement.

PMID- 25990920
TI  - Food intake and appetite control in a GH-transgenic zebrafish.
AB  - The biological actions of growth hormone (GH) are pleiotropic, including growth
      promotion, energy mobilization, gonadal development, appetite, and social
      behavior. The regulatory network for GH is complex and includes many central and
      peripheral endocrine factors as well as that from the environment. It is known
      that GH transgenesis results in increased growth, food intake, and consequent
      metabolic rates in fishes. However, the manner in which GH transgenesis alters
      the energetic metabolism in fishes has not been well explored. In order to
      elucidate these consequences, we examined the effect of GH overexpression on
      appetite control mechanisms in a transgenic zebrafish (Danio rerio) model. To
      this, we analyzed feeding behavior and the expression of the main appetite
      related genes in two different feeding periods (fed and fasting) in non
      transgenic (NT) and transgenic (T) zebrafish as well as glycaemic parameters of
      them. Our initial results have shown that NT males and females present the same
      feeding behavior and expression of main appetite-controlling genes; therefore,
      the data of both sexes were properly grouped. Following grouped data analyses, we
      compared the same parameters in NT and T animals. Feeding behavior results have
      shown that T animals eat significantly more and faster than NT siblings. Gene
      expression results pointed out that gastrointestinal (GT) cholecystokinin has a
      substantial contribution to the communication between peripheral and central
      control of food intake. Brain genes expression analyses revealed that T animals
      have a down-regulation of two strong and opposite peptides related to food
      intake: the anorexigenic proopiomelanocortin (pomc) and the orexigenic
      neuropeptide Y (npy). The down-regulation of pomc in T when compared with NT is
      an expected result, since the decrease in an anorexigenic factor might keep the
      transgenic fish hungry. The down-regulation of npy seemed to be contradictory at
      first, but if we consider the GH's capacity to elevate blood glucose, and that
      NPY is able to respond to humoral factors like glucose, this down-regulation
      makes sense. In fact, our last experiment showed that transgenics presented
      elevated blood glucose levels, confirming that npy might responded to this
      humoral factor. In conclusion, we have shown that GT responds to feeding status
      without interference of transgenesis, whereas brain responds to GH transgenesis
      without any effect of treatment. It is clear that transgenic zebrafish eat more
      and faster, and it seems that it occurs due to pomc down-regulation, since npy
      might be under regulation of the humoral factor glucose. 

PMID- 25990922
TI  - Native Liquid Extraction Surface Analysis Mass Spectrometry: Analysis of
      Noncovalent Protein Complexes Directly from Dried Substrates.
AB  - Liquid extraction surface analysis (LESA) mass spectrometry is a promising tool
      for the analysis of intact proteins from biological substrates. Here, we
      demonstrate native LESA mass spectrometry of noncovalent protein complexes of
      myoglobin and hemoglobin from a range of surfaces. Holomyoglobin, in which
      apomyoglobin is noncovalently bound to the prosthetic heme group, was observed
      following LESA mass spectrometry of myoglobin dried onto glass and polyvinylidene
      fluoride surfaces. Tetrameric hemoglobin [(alphabeta)2(4H)] was observed
      following LESA mass spectrometry of hemoglobin dried onto glass and
      polyvinylidene fluoride (PVDF) surfaces, and from dried blood spots (DBS) on
      filter paper. Heme-bound dimers and monomers were also observed. The 'contact'
      LESA approach was particularly suitable for the analysis of hemoglobin tetramers
      from DBS.

PMID- 25990923
TI  - Selective Enrichment and MALDI-TOF MS Analysis of Small Molecule Compounds with
      Vicinal Diols by Boric Acid-Functionalized Graphene Oxide.
AB  - In this study, a 4-vinylphenylboronic acid-functionalized graphene oxide (GO)
      material was prepared via atom-transfer radical polymerization (ATRP) method and
      applied for the first time as a novel matrix for the selective enrichment and
      analysis of small-molecule compounds with vicinal diols, which have been the
      focus of intense research in the field of life science, by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in positive
      ion mode. There are two main factors playing a decisive role in assisting laser
      D/I process comparing to some traditional matrices: (1) GO provides pi-conjugated
      system by itself for laser absorption and energy transfer; (2) the modified 4
      vinylphenylboronic acid can selectively capture small-molecule compounds with
      vicinal diols. The results demonstrate that the novel material has distinct
      advantages over previously reported matrices in enriching and assisting the
      highly efficient ionization of target molecules for mass spectrometry analysis.
      This work indicates a new application branch for graphene-based matrices and
      provides an alternative solution for small-molecules analysis.

PMID- 25990924
TI  - Activation of Methane by the Pyridine Radical Cation and its Substituted Forms in
      the Gas Phase.
AB  - We present an experimental study of methane activation by pyridine cation and its
      substituents in the gas phase. Mass spectrometric experiments in an ion trap
      demonstrate that pyridine cation and some of its substituent cations are able to
      react with methane. The deuterated methane experiment has confirmed that the
      hydrogen atom in the ionic product of reaction does come from methane. The
      collected information about kinetic isotope effects has been used to distinguish
      the nature of the bond activation as a hydrogen abstraction. Furthermore,
      experimental results demonstrated that the substituent groups on the pyridine
      ring can crucially influence their reactivity in methane bond activation
      processes. Density functional calculation (DFT) was employed to study the
      electronic structures of the complex and reaction mechanism of CH4+C5H5N(+). The
      calculations confirmed the hypothesis from the experimental observation, namely,
      the reaction is rapid with no energy barrier.

PMID- 25990925
TI  - Co-expression of hepatitis C virus polytope-HBsAg and p19-silencing suppressor
      protein in tobacco leaves.
AB  - CONTEXT: Plants transformed by virus-based vectors have emerged as promising
      tools to rapidly express large amounts and inexpensive antigens in transient
      condition. OBJECTIVE: We studied the possibility of transient-expression of an
      HBsAg-fused polytopic construct (HCVpc) [containing H-2d and HLA-A2-restricted
      CD8+CTL-epitopic peptides of C (Core; aa 132-142), E6 (Envelope2; aa 614-622), N
      (NS3; aa 1406-1415), and E4 (Envelope2; aa 405-414) in tandem of CE6NE4] in
      tobacco (Nicotiana tabacum) leaves for the development of a plant-based HCV
      vaccine. MATERIALS AND METHODS: A codon-optimized gene encoding the Kozak
      sequence, hexahistidine (6*His)-tag peptide, and HCVpc in tandem was designed,
      chemically synthesized, fused to HBsAg gene, and inserted into Potato virus X
      (PVX-GW) vector under the control of duplicated PVX coat protein promoter (CPP).
      The resulted recombinant plasmids (after confirmation by restriction and
      sequencing analyses) were transferred into Agrobacterium tumefaciens strain
      GV3101 and vacuum infiltrated into tobacco leaves. The effect of gene-silencing
      suppressor, p19 protein from tomato bushy stunt virus, on the expression yield of
      HCVpc-HBsAg was also evaluated by co-infiltration of a p19 expression vector.
      RESULTS: Codon-optimized gene increased adaptation index (CAI) value (from 0.61
      to 0.92) in tobacco. The expression of the HCVpc-HBsAg was confirmed by western
      blot and HBsAg-based detection ELISA on total extractable proteins of tobacco
      leaves. The expression level of the fusion protein was significantly higher in
      p19 co-agroinfiltrated plants. DISCUSSION AND CONCLUSION: The results indicated
      the possibility of expression of HCVpc-HBsAg constructs with proper protein
      conformations in tobacco for final application as a plant-derived HCV vaccine.

PMID- 25990926
TI  - Longitudinal trajectories of post-traumatic stress disorder symptoms among
      adolescents after the Wenchuan earthquake in China.
AB  - BACKGROUND: This study examines the patterns and predictors of post-traumatic
      stress disorder (PTSD) symptom trajectories among adolescent survivors following
      the Wenchuan earthquake in China. METHOD: A total of 1573 adolescent survivors
      were followed up at 6, 12, 18 and 24 months post-earthquake. Participants
      completed the Posttraumatic Stress Disorder Self-Rating Scale (PTSD-SS),
      Adolescent Self-Rating Life Events Checklist, Social Support Rate Scale, and the
      Simplified Coping Style Questionnaire. Distinct patterns of PTSD symptom
      trajectories were established through grouping participants based on time-varying
      changes of developing PTSD (i.e. reaching the clinical cut-off on the PTSD-SS).
      Multivariate logistic regressions were used to examine predictors for trajectory
      membership. RESULTS: PTSD prevalence rates at 6, 12, 18 and 24 months were 21.0,
      23.3, 13.5 and 14.7%, respectively. Five PTSD symptom trajectories were observed:
      resistance (65.3% of the sample), recovery (20.0%), relapsing/remitting (3.3%),
      delayed dysfunction (4.2%) and chronic dysfunction (7.2%). Female gender and
      senior grade were related to higher risk of developing PTSD symptoms in at least
      one time point, whereas being an only child increased the possibility of recovery
      relative to chronic dysfunction. Family members' injury/loss and witness of
      traumatic scenes could also cause PTSD chronicity. More negative life events,
      less social support, more negative coping and less positive coping were also
      common predictors for not developing resistance or recovery. CONCLUSIONS:
      Adolescents' PTSD symptoms showed an anniversary reaction. Although many
      adolescents remain euthymic or recover over time, some adolescents, especially
      those with the risk factors noted above, exhibit chronic, delayed or relapsing
      symptoms. Thus, the need for individualized intervention with these adolescents
      is indicated.

PMID- 25990927
TI  - Assisted deposition of nano-hydroxyapatite onto exfoliated carbon nanotube oxide
      scaffolds.
AB  - Electrodeposited nano-hydroxyapatite (nHAp) is more similar to biological apatite
      in terms of microstructure and dimension than apatites prepared by other
      processes. Reinforcement with carbon nanotubes (CNTs) enhances its mechanical
      properties and increases adhesion of osteoblasts. Here, we carefully studied nHAp
      deposited onto vertically aligned multi-walled CNT (VAMWCNT) scaffolds by
      electrodeposition and soaking in a simulated body fluid (SBF). VAMWCNTs are
      porous biocompatible scaffolds with nanometric porosity and exceptional
      mechanical and chemical properties. The VAMWCNT films were prepared on a Ti
      substrate by a microwave plasma chemical vapour deposition method, and then
      oxidized and exfoliated by oxygen plasma etching (OPE) to produce graphene oxide
      (GO) at the VAMWCNT tips. The attachment of oxygen functional groups was found to
      be crucial for nHAp nucleation during electrodeposition. A thin layer of plate
      like and needle-like nHAp with high crystallinity was formed without any need for
      thermal treatment. This composite (henceforth referred to as nHAp-VAMWCNT-GO)
      served as the scaffold for in vitro biomineralization when soaked in the SBF,
      resulting in the formation of both carbonate-rich and carbonate-poor globular
      like nHAp. Different steps in the deposition of biological apatite onto VAMWCNT
      GO and during the short-term biomineralization process were analysed. Due to
      their unique structure and properties, such nano-bio-composites may become useful
      in accelerating in vivo bone regeneration processes. 

PMID- 25990928
TI  - An interview with Charles Cantor: achievements and advice from 50 years of
      biotechnology expertise.
AB  - Interview with Professor Charles Cantor PhD by Claire Raison (Commissioning
      Editor) Professor Charles Cantor was awarded his PhD from the University of
      California, Berkeley (CA, USA), in 1966, and via professorships at Columbia
      University (New York, NY, USA), UC Berkeley and Boston University (Boston, MA,
      USA), went on to be Chief Scientific Officer of Sequenom (San Diego, CA, USA) and
      now retired, continues to act as consultant for more than 16 biotechnology
      companies. His research focused on inventing new techniques for solving
      biological problems, including faster DNA sequencing, better DNA amplification
      and advanced methods: for nucleic acid separation. 

PMID- 25990929
TI  - The impact of new trends in POCTs for companion diagnostics, non-invasive testing
      and molecular diagnostics.
AB  - Point-of-care diagnostics have been slowly developing over several decades and
      have taken on a new importance in current healthcare delivery for both
      diagnostics and development of new drugs. Molecular diagnostics have become a key
      driver of technology change and opened up new areas in companion diagnostics for
      use alongside pharmaceuticals and in new clinical approaches such as non-invasive
      testing. Future areas involving smartphone and other information technology
      advances, together with new developments in molecular biology, microfluidics and
      surface chemistry are adding to advances in the market. The focus for point-of
      care tests with molecular diagnostic technologies is focused on advancing
      effective applications. 

PMID- 25990930
TI  - Intraoperative passive knee kinematics during total knee arthroplasty surgery.
AB  - Surgical navigation systems for total knee arthroplasty (TKA) surgery are capable
      of capturing passive three-dimensional (3D) angular joint movement patterns
      intraoperatively. Improved understanding of patient-specific knee kinematic
      changes between pre and post-implant states and their relationship with post
      operative function may be important in optimizing TKA outcomes. However, a
      comprehensive characterization of the variability among patients has yet to be
      investigated. The objective of this study was to characterize the variability
      within frontal plane joint movement patterns intraoperatively during a passive
      knee flexion exercise. Three hundred and forty patients with severe knee
      osteoarthritis (OA) received a primary TKA using a navigation system. Passive
      kinematics were captured prior to (pre-implant), and after prosthesis insertion
      (post-implant). Principal component analysis (PCA) was used to capture
      characteristic patterns of knee angle kinematics among patients, to identify
      potential patient subgroups based on these patterns, and to examine the subgroup
      specific changes in these patterns between pre- and post-implant states. The
      first four extracted patterns explained 99.9% of the diversity within the frontal
      plane angle patterns among the patients. Post-implant, the magnitude of the
      frontal plane angle shifted toward a neutral mechanical axis in all phenotypes,
      yet subtle pattern (shape of curvature) features of the pre-implant state
      persisted.

PMID- 25990931
TI  - Inequalities in mental health in the spanish autonomous communities: a multilevel
      study.
AB  - The aim of this study was to analyze inequalities in the prevalence of poor
      mental health and their association with socioeconomic variables and with the
      care network in the Autonomous Communities in Spain. A cross-sectional multilevel
      study was performed, which analyzed individual data from the National Health
      Survey in Spain (ENS), in 2006 (n = 29,476 people over the age of 16). The
      prevalence of poor mental health was the dependent variable, measured by the
      General Health Questionnaire (GHQ-12 > = 3). Individual and contextual
      socioeconomic variables, along with mental health services in the Autonomous
      Communities, were included as independent variables. Models of multilevel
      logistic regression were used, and odds ratios (OR) were obtained, with
      confidence intervals (CI) of 95%. The results showed that there are inequalities
      in the prevalence of poor mental health in Spain, associated to contextual
      variables, such as unemployment rate (men OR 1.04 CI 1.01-1.07; women OR 1.02 CI
      1.00-1.05). On the other hand, it was observed that inequalities in the mental
      health care resources in the Autonomous Communities also have an impact on poor
      mental health. 

PMID- 25990932
TI  - Enhanced in vitro biological activity generated by surface characteristics of
      anodically oxidized titanium--the contribution of the oxidation effect.
AB  - Anodically oxidized titanium surfaces, prepared by spark discharge, have micro
      submicron surface topography and nano-scale surface chemistry, such as
      hydrophilic functional groups or hydroxyl radicals in parallel. The complexity of
      the surface characteristics makes it difficult to draw a clear conclusion as to
      which surface characteristic, of anodically oxidized titanium, is critical in
      each biological event. This study examined the in vitro biological changes,
      induced by various surface characteristics of anodically oxidized titanium with,
      or without, release of hydroxyl radicals onto the surface. Anodically oxidized
      titanium enhanced the expression of genes associated with differentiating
      osteoblasts and increased the degree of matrix mineralization by these cells in
      vitro. The phenotypes of cells on the anodically oxidized titanium were the same
      with, or without, release of hydroxyl radicals. However, the nanomechanical
      properties of this in vitro mineralized tissue were significantly enhanced on
      surfaces, with release of hydroxyl radicals by oxidation effects. In addition,
      the mineralized tissue, produced in the presence of bone morphogenetic protein-2
      on bare titanium, had significantly weaker nanomechanical properties, despite
      there being higher osteogenic gene expression levels. We show that enhanced
      osteogenic cell differentiation on modified titanium is not a sufficient
      indicator of enhanced in vitro mineralization. This is based on the inferior
      mechanical properties of mineralized tissues, without either being cultured on a
      titanium surface with release of hydroxyl radicals, or being supplemented with
      lysyl oxidase family members. 

PMID- 25990933
TI  - Prebiotic alternatives to proteins: structure and function of hyperbranched
      polyesters.
AB  - Proteins are responsible multiple biological functions, such as ligand binding,
      catalysis, and ion channeling. This functionality is enabled by proteins' three
      dimensional structures that require long polypeptides. Since plausibly prebiotic
      synthesis of functional polypeptides has proven challenging in the laboratory, we
      propose that these functions may have been initially performed by alternative
      macromolecular constructs, namely hyperbranched polymers (HBPs), during early
      stages of chemical evolution. HBPs can be straightforwardly synthesized in one
      pot processes, possess globular structures determined by their architecture as
      opposed to folding in proteins, and have documented ligand binding and catalytic
      properties. Our initial study focuses on glycerol-citric acid HBPs synthesized
      via moderate heating in the dry state. The polymerization products consisted of a
      mixture of isomeric structures of varying molar mass as evidenced by NMR, mass
      spectrometry and size-exclusion chromatography. Addition of divalent cations
      during polymerization resulted in increased incorporation of citric acid into the
      HBPs and the possible formation of cation-oligomer complexes. The chelating
      properties of citric acid govern the makeup of the resulting polymer, turning the
      polymerization system into a rudimentary smart material. 

PMID- 25990934
TI  - CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment
      during neuroinflammation.
AB  - BACKGROUND: Chemokines and chemokine receptors cooperate to promote immune cell
      recruitment to the central nervous system (CNS). In this study, we investigated
      the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine
      model of neuroinflammation. METHODS: Wild-type (WT), CXCL1(-/-), and CXCR2(-/-)
      mice each received an intracerebroventricular (i.c.v.) injection of
      lipopolysaccharide (LPS). Esterase staining and intravital microscopy were
      performed to examine neutrophil recruitment to the brain. To assess endothelial
      activation in these mice, the expression of adhesion molecules was measured via
      quantitative real-time polymerase chain reaction (PCR) and Western blotting. To
      identify the cellular source of functional CXCR2, chimeric mice were generated by
      transferring bone marrow cells between the WT and CXCR2(-/-) mice. RESULTS:
      Expression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly
      increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1
      deficiency blocked neutrophil infiltration and leukocyte recruitment in the
      cerebral microvessels. In the CXCR2(-/-) and CXCL1(-/-) mice, the cerebral
      endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was
      dramatically reduced. Furthermore, the bone marrow transfer experiments
      demonstrated that CXCR2 expression on CNS-residing cells is essential for
      cerebral endothelial activation and leukocyte recruitment. Compared with
      microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro.
      Astrocyte culture conditioned medium significantly increased the expression of
      VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner.
      Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells
      but not in microglia or astrocytes was increased following tumor necrosis factor
      alpha (TNF-alpha) stimulation. The intravenous injection of the CXCR2 antagonist
      SB225002 significantly inhibited endothelial activation and leukocyte recruitment
      to cerebral microvessels. CONCLUSIONS: CXCL1 secreted by astrocytes and
      endothelial CXCR2 play essential roles in cerebral endothelial activation and
      subsequent leukocyte recruitment during neuroinflammation.

PMID- 25990936
TI  - Ovarian Small Cell Carcinoma of Pulmonary Type Arising in Mature Cystic Teratomas
      With Metastases to the Contralateral Ovary.
AB  - A bilateral small cell ovarian carcinoma pulmonary-type (SCCOPT), arising in
      bilateral mature cystic teratomas (MCTs) presented as stage IIIB in a 37-year-old
      woman. Microscopically, tumor nests were related to the dermoid protuberance and
      expressed pancytokeratin, EMA, CD56, chromogranin A, NSE, synaptophysin, and
      SOX2. SALL4 was also focally positive. CDX2, TTF1, PAX8, CK7, CK20, and several
      neuroendocrine gut hormones were negative. Serum NSE was elevated. This case
      represents a SCCOPT arising in an MCT in the right ovary with metastasis to the
      left one also containing a synchronous MCT. Surface implants and lymphovascular
      invasion suggested metastasis from the right ovarian SCCOPT and excluded a
      metastatic origin from usual locations of small cell carcinoma (SCC). SCCOPT is
      morphologically identical to SCC elsewhere, even sharing NSE serum elevation.
      Although the tumor was closely related to teratomatous mature tissues, a complex
      immunohistochemical panel failed to provide a tissue of origin. 

PMID- 25990935
TI  - Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and
      serves as prognostic biomarker for head and neck squamous cell carcinoma
      patients.
AB  - BACKGROUND: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a
      common feature for many human malignancies and numerous studies evaluated KLK6 as
      a promising biomarker for early diagnosis or unfavorable prognosis. However, the
      expression of KLK6 in carcinomas derived from mucosal epithelia, including head
      and neck squamous cell carcinoma (HNSCC), and its mode of action has not been
      addressed so far. METHODS: Stable clones of human mucosal tumor cell lines were
      generated with shRNA-mediated silencing or ectopic overexpression to characterize
      the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with
      primary HNSCC samples from a retrospective patient cohort (n = 162) were stained
      by immunohistochemistry and the correlation between KLK6 staining and survival
      was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard
      model analysis. RESULTS: KLK6 expression was detected in head and neck tumor cell
      lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing
      in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory
      function of KLK6 on tumor cell proliferation and mobility. FaDu clones with
      silenced KLK6 expression displayed molecular features resembling epithelial-to
      mesenchymal transition, nuclear beta-catenin accumulation and higher resistance
      against irradiation. Low KLK6 protein expression in primary tumors from
      oropharyngeal and laryngeal SCC patients was significantly correlated with poor
      progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an
      independent risk factor for unfavorable clinical outcome. CONCLUSIONS: In
      summary, detection of low KLK6 expression in primary tumors represents a
      promising tool to stratify HNSCC patients with high risk for treatment failure.
      These patients might benefit from restoration of KLK6 expression or
      pharmacological targeting of signaling pathways implicated in EMT.

PMID- 25990938
TI  - The relationship between hepatitis B virus (HBV) load and levels of transforming
      growth factor beta 1 (TGF-beta1) and soluble Fas (sFas) in human immunodeficiency
      virus patients with occult HBV infection.
AB  - The aim of this study was to evaluate the correlation between hepatitis B virus
      (HBV) load and serum levels of transforming growth factor beta 1 (TGF-beta1) and
      soluble Fas (sFas) cytokines in human immunodeficiency virus (HIV) patients who
      have never been treated with antiretroviral therapy. HBV and hepatitis C virus
      (HCV) serological markers, sFas and TGF-beta1 levels, and HBV load were evaluated
      in 116 patients. While there was no correlation between TGF-beta1 levels and HBV
      load, a positive correlation between sFas levels and HBV load was observed in
      patients with occult HBV infection. 

PMID- 25990939
TI  - On the classical vibrational coherence of carbonyl groups in the selectivity
      filter backbone of the KcsA ion channel.
AB  - It has been suggested that quantum coherence in the selectivity filter of ion
      channel may play a key role in fast conduction and selectivity of ions. However,
      it has not been clearly elucidated yet why classical coherence is not sufficient
      for this purpose. In this paper, we investigate the classical vibrational
      coherence between carbonyl groups oscillations in the selectivity filter of KcsA
      ion channels based on the data obtained from molecular dynamics simulations. Our
      results show that classical coherence plays no effective role in fast ionic
      conduction. 

PMID- 25990940
TI  - Combined resistance and balance-jumping exercise reduces older women's injurious
      falls and fractures: 5-year follow-up study.
AB  - BACKGROUND AND OBJECTIVE: previously, a randomised controlled exercise
      intervention study (RCT) showed that combined resistance and balance-jumping
      training (COMB) improved physical functioning and bone strength. The purpose of
      this follow-up study was to assess whether this exercise intervention had long
      lasting effects in reducing injurious falls and fractures. DESIGN: five-year
      health-care register-based follow-up study after a 1-year, four-arm RCT. SETTING:
      community-dwelling older women in Finland. SUBJECTS: one hundred and forty-five
      of the original 149 RCT participants; women aged 70-78 years at the beginning.
      METHODS: participants' health-care visits were collected from computerised
      patient register. An injurious fall was defined as an event in which the subject
      contacted the health-care professionals or was taken to a hospital, due to a
      fall. The rate of injured fallers was assessed by Cox proportional hazards model
      (hazard ratio, HR), and the rate of injurious falls and fractures by Poisson
      regression (risk ratio, RR). RESULTS: eighty-one injurious falls including 26
      fractures occurred during the follow-up. The rate of injured fallers was 62%
      lower in COMB group compared with the controls (HR 0.38, 95% CI 0.17 to 0.85). In
      addition, COMB group had 51% less injurious falls (RR 0.49, 95% CI 0.25 to 0.98)
      and 74% less fractures (RR 0.26, 95% CI 0.07 to 0.97). CONCLUSIONS: home-dwelling
      older women who participated in a 12-month intensive multi-component exercise
      training showed a reduced incidence for injurious falls during 5-year post
      intervention period. Reduction in fractures was also evident. These long-term
      effects need to be confirmed in future studies.

PMID- 25990941
TI  - Correction: progress and developments in the turbo Grignard reagent i
      PrMgCl.LiCl: a ten-year journey.

PMID- 25990942
TI  - Vocal fold avulsion in the pediatric population: Presentation and management.
AB  - OBJECTIVE: Laryngeal injury among pediatric patients is uncommon; traumatic vocal
      fold (VF) avulsion is even more rare. The objective of this paper is to present
      the endoscopic management of a pediatric patient with VF avulsion and review the
      relevant literature. METHODS: A relevant case of a pediatric patient with a VF
      avulsion secondary to blunt laryngeal trauma who underwent successful endoscopic
      repair is presented. A comprehensive search in PubMed was conducted for cases of
      pediatric VF avulsion in the English-language literature. RESULTS: Sixteen cases
      of pediatric VF avulsion were reviewed (8 cases of external trauma and 8 cases of
      internal trauma). All cases of external laryngeal trauma presented in male
      patients and ranged in age from 5 to 15 years. Three patients had bilateral VF
      avulsions and four had unilateral avulsions. Three patients were successfully
      managed endoscopically. Four patients underwent tracheotomy; all patients were
      successfully decannulated in the postoperative period. Voice quality returned to
      normal for most patients. Clinical pearls and controversies in the evaluation and
      management of pediatric VF avulsion are presented. CONCLUSIONS: Accurate and
      timely diagnosis of pediatric VF avulsion is important. CT imaging without
      sedation should be considered in stable patients. The endoscopic approach is the
      preferred method of repair when it is amenable to the extent of injury and
      availability of expertise from both surgeon and anesthesiologist.

PMID- 25990943
TI  - Cochlear implants in children implanted in Jordan: A parental overview.
AB  - OBJECTIVE: Exploring the perspective of parents on the cochlear implant process
      in Jordan. METHODS: Sixty parents of deaf children were surveyed on the
      information gathering process prior to cochlear implant surgery, and their
      implant outcome expectations post-surgery. Whether child or parent
      characteristics may impact parents' post-surgical expectations was explored.
      RESULTS: Although parents used a variety of information sources when considering
      a cochlear implant, the ear, nose and throat doctor comprised their major source
      of information (60%). Parents received a range of information prior to cochlear
      implant but agreed (93.3%) on the need for a multidisciplinary team approach.
      Post-surgically, parents' expected major developments in the areas of spoken
      language (97%), and auditory skills (100%). Receiving education in mainstream
      schools (92%) was expected too. Parents perceived the cochlear implant decision
      as the best decision they can make for their child (98.3%). A significant
      correlation was found between parents contentment with the cochlear implant
      decision and expecting developments in the area of reading and writing (r=0.7).
      Child's age at implantation and age at hearing loss diagnosis significantly
      affected parents' post-implant outcome expectations (p<0.05). CONCLUSION: Despite
      the general satisfaction from the information quantity and quality prior to
      cochlear implant, parents agree on the need for a comprehensive multidisciplinary
      team approach during the different stages of the cochlear implant process.
      Parents' education about cochlear implants prior to the surgery can affect their
      post-surgical outcome expectations. The parental perspective presented in this
      study can help professionals develop better understanding of parents' needs and
      expectations and henceforth improve their services and support during the
      different stages of the cochlear implant process.

PMID- 25990945
TI  - MicroRNAs and lncRNAs in senescence: A re-view.
AB  - Cellular senescence is a stress response to a variety of extrinsic and intrinsic
      insults that cause genomic or epigenomic perturbations. It is now widely
      recognized as a potent tumor suppressor mechanism as well as a biological process
      impacting aging and organismal development. Like other cell fate decisions,
      senescence is executed and maintained by an intricate network of transcription
      factors (TFs), chromatin modifiers, and noncoding RNAs (ncRNAs). Altogether,
      these factors cooperate to implement the gene expression program that initiates
      and sustains the senescent phenotype. In the context of senescence, microRNAs
      (miRs) and long ncRNAs have been found to play regulatory roles at both the
      transcriptional and post-transcriptional levels. In this review, we discuss
      recent developments in the field and point toward future research directions to
      gain a better understanding of ncRNAs in senescence.

PMID- 25990946
TI  - EGF-induced dynamics of NF-kappaB and F-actin in A431 cells spread on
      fibronectin.
AB  - To evaluate the role of actin cytoskeleton in the regulation of NF-kappaB
      transcription factor, we analyzed its involvement in the intracellular transport
      and nuclear translocation of the NF-kappaB RelA/p65 subunit in A431 epithelial
      cells stimulated with fibronectin and EGF. Live cell imaging and confocal
      microscopy showed that EGF activated the movement of RelA/p65 in the cytoplasm.
      Upon cell adhesion to fibronectin, RelA/p65 concentrated onto stress fibers, and
      EGF stimulated its subsequent allocation to membrane ruffles, newly organized
      stress fibers, and discrete cytoplasmic actin-rich patches. These patches also
      contained alpha-actinin-1 and alpha-actinin-4, vinculin, paxillin, alpha-tubulin,
      and PI3-kinase. Cytochalasin D treatment resulted in RelA/p65 redistribution to
      actin-containing aggregates, with the number of cells with RelA/p65-containing
      clusters in the cytoplasm increasing under the effect of EGF. Furthermore, EGF
      proved to induce RelA/p65 accumulation in the nucleus after cell pretreatment
      with actin-stabilizing and actin-destabilizing agents, which was accompanied by
      changes in its DNA-binding activity after either EGF stimulation or cytochalasin
      D treatment. Thus, EGF treatment of A431 cells results in simultaneous nuclear
      RelA/p65 translocation and cytoplasmic redistribution, with part of RelA/p65 pool
      forming a very tight association with actin-rich structures. Apparently, nuclear
      transport is independent on drug stabilization or destabilization of the actin.

PMID- 25990947
TI  - Method of preparing an equimolar DNA mixture for one-step DNA assembly of over 50
      fragments.
AB  - In the era of synthetic biology, techniques for rapidly constructing a designer
      long DNA from short DNA fragments are desired. To realize this, we attempted to
      establish a method for one-step DNA assembly of unprecedentedly large numbers of
      fragments. The basic technology is the Ordered Gene Assembly in Bacillus subtilis
      (OGAB) method, which uses the plasmid transformation system of B. subtilis. Since
      this method doesn't require circular ligation products but needs tandem repeat
      ligation products, the degree of deviation in the molar concentration of the
      material DNAs is the only determinant that affects the efficiency of DNA
      assembly. The strict standardization of the size of plasmids that clone the DNA
      block and the measurement of the block in the state of intact plasmid improve the
      reliability of this step, with the coefficient of variation of the molar
      concentrations becoming 7%. By coupling this method with the OGAB method, one
      step assembly of more than 50 DNA fragments becomes feasible. 

PMID- 25990948
TI  - Conceptions of decision-making capacity in psychiatry: interviews with Swedish
      psychiatrists.
AB  - BACKGROUND: Decision-making capacity is a key concept in contemporary healthcare
      ethics. Previous research has mainly focused on philosophical, conceptual issues
      or on evaluation of different tools for assessing patients' capacity. The aim of
      the present study is to investigate how the concept and its normative role are
      understood in Swedish psychiatric care. Of special interest for present purposes
      are the relationships between decisional capacity and psychiatric disorders and
      between health law and practical ethics. METHODS: Eight in-depth interviews were
      conducted with Swedish psychiatrists. The interviews were analysed according to
      descriptive qualitative content analysis in which categories and sub-categories
      were distilled from the material. RESULTS: Decision-making capacity was seen as
      dependent on understanding, insight, evaluation, reasoning, and abilities related
      to making and communicating a choice. However, also the actual content of the
      decision was held as relevant. There was an ambivalence regarding the
      relationship between psychiatric disorders and capacity and a tendency to regard
      psychiatric patients who made unwise treatment decisions as decisionally
      incapable. However, in cases relating to patients with somatic illnesses, the
      assumption was rather that patients who made unwise decisions were imprudent but
      yet decisionally capable. CONCLUSIONS: The respondents' conceptions of decision
      making capacity were mainly in line with standard theories. However, the idea
      that capacity also includes aspects relating to the content of the decision
      clearly deviates from the standard view. The tendency to regard imprudent choices
      by psychiatric patients as betokening lack of decision-making capacity differs
      from the view taken of such choices in somatic care. This difference merits
      further investigations.

PMID- 25990949
TI  - Vesicle dynamics in uniform electric fields: squaring and breathing.
AB  - We computationally investigate the dynamics of a vesicle exposed to uniform DC or
      AC electric fields. We employ the two-dimensional boundary integral method in
      order to simulate vesicle deformation under experimental conditions where
      peculiar drum-like ("squared") shapes have been observed. The vesicle membrane is
      modeled as an infinitely thin, capacitive, area-incompressible interface, with
      the surrounding fluids acting as leaky dielectrics. Our simulations capture the
      "squaring" phenomenon, in which vesicles deform into rectangular profiles with
      corner-like regions of high curvature, as vesicles undergo dynamic transitions
      between oblate and prolate ellipsoidal shapes. 

PMID- 25990950
TI  - Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non
      small cell lung cancer patients: A systematic review.
AB  - Recently, non-small cell lung cancer (NSCLC) has been partly subclassified into
      molecularly-defined oncogene "addicted" tumors for which targeted agents are
      available. Tyrosine kinase inhibitors (TKI) are currently approved for patients
      with an activating epidermal growth factor receptor (EGFR) mutation or anaplastic
      lymphoma kinase (ALK) rearrangement. In these patients, brain metastases are
      often the first site of progression while on TKI treatment. The TKI may however
      still be active on extra-cranial sites and clinicians are thus faced with the
      question if the TKI may be continued during cranial radiotherapy. Advantages of
      combining TKI with cranial radiotherapy would be a possible synergistic effect on
      the brain metastases and the prevention of a systemic disease flare-up. A
      disadvantage is the possibly increased risk of (neuro)toxicity. The present
      systematic review addresses the toxicity of combining TKI with cranial
      radiotherapy in NSCLC patients.

PMID- 25990951
TI  - Blood borne virus (BBV) testing in a university setting in North-East Scotland: a
      pilot initiative.

PMID- 25990952
TI  - Synthesis and antibacterial activity of 4" or 6"-alkanoylamino derivatives of
      arbekacin.
AB  - Arbekacin, an aminoglycoside antibiotic, is an important drug because it shows a
      potent efficacy against methicillin-resistant Staphylococcus aureus. However,
      resistance to arbekacin, which is caused mainly by the bifunctional
      aminoglycoside-modifying enzyme, has been observed, becoming a serious problem in
      medical practice. To create new arbekacin derivatives active against resistant
      bacteria, we modified the C-4" and 6" positions of its 3-aminosugar portion.
      Regioselective amination of the 6"-position gave 6"-amino-6"-deoxyarbekacin (1),
      and it was converted to a variety of 6"-N-alkanoyl derivatives (6a-z).
      Furthermore, regioselective modifications of the 4"-hydroxyl group were performed
      to give 4"-deoxy-4"-epiaminoarbekacin (2) and its 4"-N-alkanoyl derivatives (12
      and 13). Their antibacterial activity against S. aureus, including arbekacin
      resistant bacteria, was evaluated. It was observed that 6"-amino-6"-N-[(S)-4
      amino-2-hydroxybutyryl]-6"-deoxyarbekacin (6o) showed excellent antibacterial
      activity, even better than arbekacin. 

PMID- 25990953
TI  - Evaporative light scattering quantification of natural products possessing a
      carbon-phosphorus bond.

PMID- 25990954
TI  - Inhibitory activities of the marine streptomycete-derived compound SF2446A2
      against Chlamydia trachomatis and Schistosoma mansoni.
AB  - Infectious diseases caused by chlamydia or schistosomes are a major health
      problem worldwide, and particularly so in developing countries. The lack of
      appropriate vaccines renders the search for potent natural products against these
      disease-causing agents an urgent endeavor. Sponge-associated actinomycetes
      represent a rich reservoir for natural products. Among them, members of the genus
      Streptomyces are capable of synthesizing an impressive array of diverse natural
      products with a wide variety of biological activities. The naphthacene glycoside
      SF2446A2 was isolated from the calcium alginate beads culture of Streptomyces sp.
      strain RV15 that had originally been obtained from the Mediterranean sponge
      Dysidea tupha. Its structure was identified by spectroscopic analysis and MS and
      comparison with the literature data. SF2446A2 showed inhibitory activity against
      Chlamydia trachomatis and was able to inhibit the primary infection in a dose
      dependent manner, as well as progeny formation. Moreover, it caused disruptive
      effects on the surface area of Schistosoma mansoni and affected the gonads by
      impairing oogenesis and spermatogenesis. Our current study demonstrates that
      sponge-associated actinomycetes are capable of providing compounds with new
      pharmacological activities and with relevance to drug discovery. 

PMID- 25990956
TI  - Development of a high-speed MALDI-triple quadrupole mass spectrometric method for
      the determination of 3,4-methylenedioxymethamphetamine (MDMA) in oral fluid.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is still a widely used illicit
      designer drug and its detection in different matrices is of major importance for
      forensic purposes (e.g. driving under the influence) as well as for workplace
      drug testing or abstinence control. Established analytical methods for the
      determination of MDMA are mainly employing high performance liquid chromatography
      (HPLC) or gas chromatography (GC) coupled to mass spectrometric detection. Matrix
      assisted laser desorption/ionization-triple quadrupole-tandem mass spectrometry
      (MALDI-QqQ-MS/MS) is so far rarely used in forensics and offers an ultrafast high
      throughput platform. The QuantisalTM Oral Fluid Collection Device was used for
      sample collection. After addition of the deuterated internal standard and a
      carbonate buffer (0.75 M Na2 CO3 ), oral fluid samples were liquid-liquid
      extracted (ButOAc/EtOAc, 1:1). As little as 1 microlitre of a mixture of this
      extract and the MALDI matrix (alpha-cyano-4-hydroxycinnamic acid) was spotted
      onto the MALDI plate and could directly be analyzed. With MALDI omitting
      chromatographic separation, very short analysis times of about 10 s per sample
      were possible. The method was developed and validated according to international
      guidelines including specificity, recovery, matrix effects, accuracy and
      precision, stabilities and limit of quantification. All validation criteria were
      fulfilled except for ion suppression/enhancement. Comparison with a routine
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method showed good
      agreement of the results. Applicability of the method was shown by analyzing
      about 250 oral fluid samples collected after controlled administration of 125 mg
      MDMA in a pharmacokinetic study. The whole lot of samples could be analyzed in
      less than 1 h, proving the ultra-high-speed of the method.

PMID- 25990955
TI  - Identification of small-molecule inhibitors against SecA by structure-based
      virtual ligand screening.
AB  - The rapid rise of antibiotic-resistant bacteria is one of the major concerns in
      modern medicine. Therefore, to treat bacterial infections, there is an urgent
      need for new antibacterials-preferably directed against alternative bacterial
      targets. One such potential target is the preprotein translocation motor SecA.
      SecA is a peripheral membrane ATPase and a key component of the Sec secretion
      pathway, the major route for bacterial protein export across or into the
      cytoplasmic membrane. As SecA is essential for bacterial viability, ubiquitous
      and highly conserved in bacteria, but not present in eukaryotic cells, it
      represents an attractive antibacterial target. Using an in silico approach, we
      have defined several potentially druggable and conserved pockets on the surface
      of SecA. We show that three of these potentially druggable sites are important
      for SecA function. A starting collection of ~500 000 commercially available small
      molecules was virtually screened against a predicted druggable pocket in the
      preprotein-binding domain of Escherichia coli SecA using a multi-step virtual
      ligand screening protocol. The 1040 top-scoring molecules were tested in vitro
      for inhibition of the translocation ATPase activity of E. coli SecA. Five
      inhibitors of the translocation ATPase, and not of basal or membrane ATPase, were
      identified with IC50 values <65 MUm. The most potent inhibitor showed an IC50 of
      24 MUm. The antimicrobial activity was determined for the five most potent SecA
      inhibitors. Two compounds were found to possess weak antibacterial activity (IC50
      ~198 MUm) against E. coli, whereas some compounds showed moderate antibacterial
      activity (IC50 ~100 MUm) against Staphylococcus aureus. 

PMID- 25990957
TI  - ERK reinforces actin polymerization to power persistent edge protrusion during
      motility.
AB  - Cells move through perpetual protrusion and retraction cycles at the leading
      edge. These cycles are coordinated with substrate adhesion and retraction of the
      cell rear. We tracked spatial and temporal fluctuations in the molecular
      activities of individual moving cells to elucidate how extracellular signal
      regulated kinase (ERK) signaling controlled the dynamics of protrusion and
      retraction cycles. ERK is activated by many cell surface receptors, and we found
      that ERK signaling specifically reinforced cellular protrusions so that they
      translated into rapid, sustained forward motion of the leading edge. Using
      quantitative fluorescent speckle microscopy and cross-correlation analysis, we
      showed that ERK controlled the rate and timing of actin polymerization by
      promoting the recruitment of the actin nucleator Arp2/3 to the leading edge.
      These findings support a model in which surges in ERK activity induced by
      extracellular cues enhance Arp2/3-mediated actin polymerization to generate
      protrusion power phases with enough force to counteract increasing membrane
      tension and to promote sustained motility. 

PMID- 25990958
TI  - A molecular switch in the scaffold NHERF1 enables misfolded CFTR to evade the
      peripheral quality control checkpoint.
AB  - The peripheral protein quality control (PPQC) checkpoint removes improperly
      folded proteins from the plasma membrane through a mechanism involving the E3
      ubiquitin ligase CHIP (carboxyl terminus of Hsc70 interacting protein). PPQC
      limits the efficacy of some cystic fibrosis (CF) drugs, such as VX-809, that
      improve trafficking to the plasma membrane of misfolded mutants of the CF
      transmembrane conductance regulator (CFTR), including F508del-CFTR, which retains
      partial functionality. We investigated the PPQC checkpoint in lung epithelial
      cells with F508del-CFTR that were exposed to VX-809. The conformation of the
      scaffold protein NHERF1 (Na(+)/H(+) exchange regulatory factor 1) determined
      whether the PPQC recognized "rescued" F508del-CFTR (the portion that reached the
      cell surface in VX-809-treated cells). Activation of the cytoskeletal regulator
      Rac1 promoted an interaction between the actin-binding adaptor protein ezrin and
      NHERF1, triggering exposure of the second PDZ domain of NHERF1, which interacted
      with rescued F508del-CFTR. Because binding of F508del-CFTR to the second PDZ of
      NHERF1 precluded the recruitment of CHIP, the coexposure of airway cells to Rac1
      activator nearly tripled the efficacy of VX-809. Interference with the NHERF1
      ezrin interaction prevented the increase of efficacy of VX-809 by Rac1
      activation, but the actin-binding domain of ezrin was not required for the
      increase in efficacy. Thus, rather than mainly directing anchoring of F508del
      CFTR to the actin cytoskeleton, induction of ezrin activation by Rac1 signaling
      triggered a conformational change in NHERF1, which was then able to bind and
      stabilize misfolded CFTR at the plasma membrane. These insights into the cell
      surface stabilization of CFTR provide new targets to improve treatment of CF. 

PMID- 25990960
TI  - Software for the analysis and visualization of deep mutational scanning data.
AB  - BACKGROUND: Deep mutational scanning is a technique to estimate the impacts of
      mutations on a gene by using deep sequencing to count mutations in a library of
      variants before and after imposing a functional selection. The impacts of
      mutations must be inferred from changes in their counts after selection. RESULTS:
      I describe a software package, dms_tools, to infer the impacts of mutations from
      deep mutational scanning data using a likelihood-based treatment of the mutation
      counts. I show that dms_tools yields more accurate inferences on simulated data
      than simply calculating ratios of counts pre- and post-selection. Using
      dms_tools, one can infer the preference of each site for each amino acid given a
      single selection pressure, or assess the extent to which these preferences change
      under different selection pressures. The preferences and their changes can be
      intuitively visualized with sequence-logo-style plots created using an extension
      to weblogo. CONCLUSIONS: dms_tools implements a statistically principled approach
      for the analysis and subsequent visualization of deep mutational scanning data.

PMID- 25990961
TI  - Small joints replacement for hand osteoarthritis: a systematic review.
AB  - INTRODUCTION: Small joints replacement is a valid treatment for moderate to
      severe osteoarthritis of the hand. Several design and materials are now available
      for prostethic procedures with very different clinical and functional outcomes.
      SOURCES OF DATA: An online search was carried out using Medline, Cochrane and
      Google scholar online databases, searching for studies on small joints
      replacement in hand surgery. AREAS OF AGREEMENT: Good functional and clinical
      outcomes can be achieved with silicone and pyrolitic carbon implants, either for
      trapeziometacarpal and metacarpophalangeal joints. In particular, the silicone
      spacer seems to be very effective for trapeziometacarpal osteoarthrosis, while
      the pyrolitic carbon total joint prosthesis produces excellent outcomes if used
      for metacarpophalangeal replacement. Major complications, such as persistent pain
      and implant loosening, have still a variable rate of occurrence. AREAS OF
      CONTROVERSY: Heterogeneity in the methodology of the assessments in the studies
      reviewed and the implants and techniques involved makes it difficult to carry out
      a complete and effective comparative analysis of the data collected. GROWING
      POINTS: Larger cohorts treated with the same implant should be investigated in
      better designed trials, to draw more clinically relevant conclusions from the
      evidences presented. Better methodology is also a goal to achieve, since the
      average Coleman Methodology Score measured for the articles included was 54.9 out
      of 100. RESEARCH: More and better designed studies are needed to produce clear
      guidelines to define the better implant in terms of clinical outcomes, function
      and complications for trapeziometacarpal and metacarpophalangeal joints.

PMID- 25990959
TI  - The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative
      feedback of the T cell receptor pathway.
AB  - T cell activation by antigens binding to the T cell receptor (TCR) must be
      properly regulated to ensure normal T cell development and effective immune
      responses to pathogens and transformed cells while avoiding autoimmunity. The Src
      family kinase Lck and the Syk family kinase ZAP-70 (zeta chain-associated protein
      kinase of 70 kD) are sequentially activated in response to TCR engagement and
      serve as critical components of the TCR signaling machinery that leads to T cell
      activation. We performed a mass spectrometry-based phosphoproteomic study
      comparing the quantitative differences in the temporal dynamics of
      phosphorylation in stimulated and unstimulated T cells with or without inhibition
      of ZAP-70 catalytic activity. The data indicated that the kinase activity of ZAP
      70 stimulates negative feedback pathways that target Lck and thereby modulate the
      phosphorylation patterns of the immunoreceptor tyrosine-based activation motifs
      (ITAMs) of the CD3 and zeta chain components of the TCR and of signaling
      molecules downstream of Lck, including ZAP-70. We developed a computational model
      that provides a mechanistic explanation for the experimental findings on ITAM
      phosphorylation in wild-type cells, ZAP-70-deficient cells, and cells with
      inhibited ZAP-70 catalytic activity. This model incorporated negative feedback
      regulation of Lck activity by the kinase activity of ZAP-70 and predicted the
      order in which tyrosines in the ITAMs of TCR zeta chains must be phosphorylated
      to be consistent with the experimental data. 

PMID- 25990962
TI  - Parvovirus B19V infection in Israel: prevalence and occurrence of acute infection
      between 2008 and 2013.
AB  - Differences in the seroprevalence and unique pattern of parvovirus B19 (B19V)
      acute infections have been documented around the world. This study was conducted
      to estimate the seroprevalence of anti-parvovirus B19V IgG antibodies in the
      Israeli population and to assess the pattern of acute infection based on data
      from two laboratories in Israel. The overall IgG prevalence in the 1008
      representative sera samples was 61.4% and the age-adjusted prevalence rate was
      58.2%. Seropositivity was significantly associated with age, ranging from 25.7%
      in children aged 20 years. While no significant differences in seropositivity
      were detected between sexes and population groups, significantly lower
      seroprevalence was observed in older Jews born in Africa or Asia. Acute infection
      rates of 4.1% (234 cases) were found based on the positive IgM results identified
      in samples from 5663 individuals collected between 2008 and 2013. Annual peaks of
      infection were observed in 2008 and 2011-2012 and major seasonal peak of B19V IgM
      positivity was identified in June each year. The number of requests for B19V
      serology was significantly higher for women aged 20-39 years while the majority
      IgM-positive cases were identified in young children. With more than 30% of the
      adult population being susceptible to B19V infection, monitoring B19V status
      should be considered in specific risk groups such as pregnant women.

PMID- 25990963
TI  - Penetratin-Mediated Transepithelial Insulin Permeation: Importance of Cationic
      Residues and pH for Complexation and Permeation.
AB  - Penetratin is a widely used carrier peptide showing promising potential for
      mucosal delivery of therapeutic proteins. In the present study, the importance of
      specific penetratin residues and pH was investigated with respect to complexation
      with insulin and subsequent transepithelial insulin permeation. Besides
      penetratin, three analogues were studied. The carrier peptide-insulin complexes
      were characterized in terms of size and morphology at pH 5, 6.5, and 7.4 by
      dynamic light scattering (DLS) and transmission electron microscopy (TEM),
      respectively. At pH 7.4 mainly very large complexes were present, while much
      smaller complexes dominated at pH 5. Presence of arginine residues in the carrier
      peptide proved to be a prerequisite for complexation with insulin as well as for
      enhanced transepithelial insulin permeation in vitro. Rearrangement of tryptophan
      residues resulted in significantly increased insulin permeation as compared to
      that of the parent penetratin. In general, pre-complexation with penetratin and
      its analogues at pH 5 gave rise to increased insulin permeation as compared to
      that observed at pH 7.4; this finding was further supported by a preliminary in
      vivo study using the parent penetratin.

PMID- 25990964
TI  - Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of
      Fimasartan in Rats, Dogs, and Humans.
AB  - Enterohepatic recirculation (EHC) can greatly enhance plasma drug exposures and
      therapeutic effects. This study aimed to develop a population pharmacokinetic
      model that can simultaneously characterize the extent and time-course of EHC in
      three species using fimasartan, a novel angiotensin II receptor blocker, as a
      model drug. All fimasartan plasma concentration profiles in 32 rats (intravenous
      doses, 0.3-3 mg/kg; oral doses, 1-10 mg/kg), 34 dogs (intravenous doses, 0.3-1
      mg/kg; oral doses, 1-10 mg/kg), and 42 healthy volunteers (single or multiple
      oral doses, 20-480 mg) were determined via liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and simultaneously modeled in S-ADAPT. The proposed model
      quantitatively characterized EHC in three species after oral and intravenous
      dosing. The median (range) fraction of drug undergoing recirculation was 76.3%
      (64.9-88.7%) in rats, 33.3% (24.0-45.9%) in dogs, and 65.6% (56.5-72.0%) in
      humans. In the presence compared with the absence of EHC, the area under the
      curve in plasma was predicted to be 4.22-fold (2.85-8.85) as high in rats, 1.50
      fold (1.32-1.85) in dogs, and 2.91-fold (2.30-3.57) in humans. The modeled oral
      bioavailability in rats (median (range), 38.7% (20.0-59.8%)) and dogs (median,
      7.13% to 15.4%, depending on the formulation) matched the non-compartmental
      estimates well. In humans, the predicted oral bioavailability was 25.1% (15.1
      43.9%) under fasting and 18.2% (12.2-31.0%) under fed conditions. The
      allometrically scaled area under the curve predicted from rats was 420 ng.h/mL
      for 60 mg fimasartan compared with 424 +/- 63 ng.h/mL observed in humans. The
      developed population pharmacokinetic model can be utilized to characterize the
      impact of EHC on plasma drug exposure in animals and humans.

PMID- 25990965
TI  - Creep-feeding to stimulate metabolic imprinting in nursing beef heifers: impacts
      on heifer growth, reproductive and physiological variables.
AB  - This experiment compared growth, physiological, and reproductive responses of
      beef heifers with (MI) or without (CON) access to a creep-feeder, as a manner to
      stimulate metabolic imprinting while nursing their dams. On day 0, 60 Angus *
      Hereford heifers were ranked by BW and age (140 +/- 3 kg and 68+/-3 days), and
      assigned to pairs so all ranking criteria were similar between heifers within
      each pair. On day 1, pairs were randomly assigned to MI (n=15) or CON (n=15).
      From day 1 to 51, MI pairs and their dams were allocated to 15 drylot pens where
      heifers had ad libitum access to a corn-based supplement through a creep-feeder.
      The CON pairs and their dams were maintained in an adjacent single drylot pen.
      From day 52 to 111, treatments were managed as a single group on a semiarid range
      pasture. On day 111, heifers were weaned and allocated to two pastures (one
      pasture/treatment), receiving hay and a corn-based concentrate until day 326.
      Heifer BW was recorded before and at the end of the creep-feeding period (day 1
      to 51), and on days 112 and 326. On days 0, 51, 111, 187, 261, and 325, jugular
      blood was collected and real-time ultrasonography for longissimus muscle depth
      and backfat thickness assessment was performed. Blood was also collected every 10
      days from days 113 to 323 for puberty evaluation via plasma progesterone. Liver
      and subcutaneous fat biopsies were performed on days 51, 111, 261 and 325.
      Average daily gain was greater (P<0.01) for MI than CON from day 1 to 51, tended
      (P=0.09) to be greater for CON than MI from day 112 to 326, while BW on day 326
      was similar between treatments. On day 51, MI had greater (P ? 0.01) plasma IGF-I
      and glucose concentrations, as well as mRNA expression of hepatic pyruvate
      carboxylase and adipose fatty acid synthase than CON. On days 261 and 325, plasma
      insulin concentrations were greater (P ? 0.03) in CON than MI. Mean mRNA
      expression of hepatic IGF-I and adipose peroxisome proliferator-activated
      receptor gamma were greater (P ? 0.05) in MI than CON. No treatment effects were
      detected for puberty attainment rate. In conclusion, supplementing nursing
      heifers via creep-feeding for 50 days altered physiological and biochemical
      variables suggestive of a metabolic imprinting effect, but did not hasten their
      puberty attainment.

PMID- 25990966
TI  - MicroRNA-184 Deregulated by the MicroRNA-21 Promotes Tumor Malignancy and Poor
      Outcomes in Non-small Cell Lung Cancer via Targeting CDC25A and c-Myc.
AB  - BACKGROUND: MicroRNA (miR)-184 has been reported to have a dual role in human
      cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC)
      remains unclear. METHODS: Wild-type or mutant CDC25A promoters were constructed
      by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit
      CDC25A expression at post-transcription level. Boyden chamber assay was used to
      assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and
      c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21,
      PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time
      PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall
      survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan-Meier and
      Cox regression analysis. RESULTS: MiR-184 suppressed CDC25A expression by
      enhancing the instability of its mRNA as a result of miR-184 binding to its
      coding region. An increase in CDC25A expression by means of a reduction in miR
      184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c
      Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4
      reduction is responsible for cell invasiveness. Among patients, miR-184
      expression in lung tumors was found to correlate negatively with CDC25A mRNA, c
      Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA
      expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited
      shorter OS and RFS periods than their counterparts. The worst OS and RFS were
      observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184
      /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors.
      CONCLUSIONS: MiR-184 as a tumor suppressor miR inhibits cell proliferation and
      invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict
      worse prognosis in NSCLC patients.

PMID- 25990968
TI  - Detailed pathological examination of completion node dissection specimens and
      outcome in melanoma patients with minimal (<0.1 mm) sentinel lymph node
      metastases.
AB  - BACKGROUND: Nonsentinel lymph nodes (NSLNs) are rarely involved in patients with
      minimal volume melanoma metastases in sentinel lymph nodes (SLNs). Therefore, it
      has been suggested that completion lymph node dissection (CLND) is not required.
      However, the lack of routine immunohistochemical staining and multiple sectioning
      may have led to failure to identify additional positive nodes. The present study
      sought to more reliably determine the tumor status of NSLNs in patients with
      minimally involved SLNs and their clinical outcome. METHODS: A total of 21 tumor
      negative CLND specimens from 20 patients with SLN metastases of <0.1 mm in
      diameter treated between 1991 and 2013 were examined with a more detailed
      pathologic protocol (five new sections stained with/for H&E, S-100, HMB45, Melan
      A, and H&E). Clinical follow-up data were also obtained. RESULTS: Of the 343
      examined NSLNs, 1 was found to harbor a 0.18-mm subcapsular sinus metastasis. No
      metastases were identified in the other NSLNs. Median follow-up was 48 months
      (range 17-130 months). Six patients (30 %) developed a recurrence. At the end of
      follow-up, 15 patients (75 %) were alive without sign of melanoma recurrence and
      5 patients (25 %) had died of melanoma. Estimated 5-year melanoma-specific
      survival was 64 %. The patient with the additional positive NSLN remains without
      recurrence after 130 months follow-up. CONCLUSIONS: Although the risk of
      additional nodal involvement is low, detailed pathologic examination may identify
      NSLN metastases not identified using routine protocols. Therefore, nodal
      clearance appears to be the safest option for these patients, pending the results
      of prospective trials.

PMID- 25990967
TI  - Contrast-Enhanced Ultrasound Biopsy of Sentinel Lymph Nodes in Patients with
      Breast Cancer: Implications for Axillary Metastases and Conservation.
AB  - BACKGROUND: In breast cancer patients, sentinel lymph nodes (SLN) can be
      identified in the breast clinic using contrast-enhanced ultrasound (CEUS). This
      study aimed to characterize and compare the extent of axillary metastases in
      patients with either a benign or malignant SLN core biopsy at the end of surgical
      treatment. METHODS: Between 2009 and 2014, prospective data were collected on
      consecutive patients who underwent targeted core biopsy of SLN identified using
      CEUS in the breast clinic. Patients with abnormal lymph nodes (LN) detected on
      grey-scale ultrasound were not included. Patients whose initial SLN core biopsy
      was benign were compared with those who had a malignant SLN core biopsy. RESULTS:
      555 patients with invasive breast cancer had SLN successfully identified and core
      biopsied. 487 had a benign SLN core biopsy and 427 (88 %) did not have metastases
      found in surgically excised SLN. Only 2 % of patients with an initial benign SLN
      core biopsy were found to have 2 or more LN macrometastases. 68 patients had a
      malignant SLN core biopsy and 52 % had 2 or more LN macrometastases. The total
      volume of LN metastases was higher in the group of patients who had an initial
      malignant SLN core biopsy (P < 0.001). CONCLUSIONS: Patients with a normal grey
      scale ultrasound and benign SLN core biopsy are unlikely to have extensive
      axillary disease and may be ideally suited for axillary conservation. The
      decision to omit axillary LN dissection for patients with a malignant SLN core
      biopsy must be carefully considered because many will have undetected high-volume
      metastases.

PMID- 25990969
TI  - Replica state exchange metadynamics for improving the convergence of free energy
      estimates.
AB  - Metadynamics (MTD) is a powerful enhanced sampling method for systems with rugged
      energy landscapes. It constructs a bias potential in a predefined collective
      variable (CV) space to overcome barriers between metastable states. In bias
      exchange MTD (BE-MTD), multiple replicas approximate the CV space by exchanging
      bias potentials (replica conditions) with the Metropolis-Hastings (MH) algorithm.
      We demonstrate that the replica-exchange rates and the convergence of free energy
      estimates of BE-MTD are improved by introducing the infinite swapping (IS) or the
      Suwa-Todo (ST) algorithms. Conceptually, IS and ST perform transitions in a
      replica state space rather than exchanges in a replica condition space. To
      emphasize this, the proposed scheme is called the replica state exchange MTD (RSE
      MTD). Benchmarks were performed with alanine polypeptides in vacuum and water.
      For the systems tested in this work, there is no significant performance
      difference between IS and ST.

PMID- 25990970
TI  - Lgr5+ amacrine cells possess regenerative potential in the retina of adult mice.
AB  - Current knowledge indicates that the adult mammalian retina lacks regenerative
      capacity. Here, we show that the adult stem cell marker, leucine-rich repeat
      containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of
      adult mice. Lgr5(+) cells are generated at late stages of retinal development and
      exhibit properties of differentiated amacrine interneurons (amacrine cells).
      Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal
      cells in the adult stage. The generation of new retinal cells, including retinal
      neurons and Muller glia from Lgr5(+) amacrine cells, begins in early adulthood
      and continues as the animal ages. Together, these findings suggest that the
      mammalian retina is not devoid of regeneration as previously thought. It is
      rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative
      source. The identification of such cells in the mammalian retina may provide new
      insights into neuronal regeneration and point to therapeutic opportunities for
      age-related retinal degenerative diseases. 

PMID- 25990972
TI  - The foreseeable future.

PMID- 25990973
TI  - Business continuity management into operational risk management: Assimilation is
      imminent ... resistance is futile!

PMID- 25990971
TI  - Characterization of TLR2, NOD2, and related cytokines in mammary glands infected
      by Staphylococcus aureus in a rat model.
AB  - BACKGROUND: Staphylococcus aureus causes subclinical mastitis as well as
      persistent and chronic infections in cattle. Bovine mastitis induced by S. aureus
      is often refractory to antibiotic treatment. Local innate immune defenses play an
      important role in eliminating the invading bacteria. TLR2 and NOD2 are important
      pathogen recognition receptors, but their functions have not been investigated in
      the context of early stages of mastitis. The present study examined TLR2, NOD2,
      and related cytokines in mammary glands infection induced by S. aureus at early
      stages in a rat mastitis model. FINDINGS: All inoculated mammary glands developed
      mastitis. Acute changes were induced in mammary tissues infected with S. aureus
      at early stages and then chronic infections persisted until the end of the
      experiment. TLR2 and NOD2 mRNA expression increased significantly after
      inoculation with S. aureus. The expression levels of cytokine mRNAs, including
      TNF-alpha, IL-1beta, IL-6, IL-10, and CXCL1, also increased. TGF-beta1 expression
      was suppressed at early phase and IFN-gamma mRNA expression increased
      significantly at a later stage. CONCLUSIONS: Mammary innate immune responses were
      activated after S. aureus inoculation. TLR2, NOD2, and inflammatory cytokines
      (TNF-alpha, IL-1beta, IL-6, CXCL1, IL-10, TGF-beta1, and IFN-gamma) are involved
      in the response to mastitis induced by S. aureus.

PMID- 25990974
TI  - Is there a business continuity plan for emergencies like an Ebola outbreak or
      other pandemics?
AB  - During emergencies, the health system will be overwhelmed and challenged by
      various factors like staff absenteeism and other limited resources. More than
      half of the workforce in Liberia has been out of work since the start of the
      Ebola outbreak. It is vital to continue essential services like maternal and
      child health care, emergency care and others while responding to emergencies like
      an Ebola outbreak other pandemic or disaster. Having a business continuity plan
      (BCP) and involving various sectors during planning and implementing the plan
      during a crisis will assist in providing essential services to the public. An
      established BCP will not only help the continuity of services, it also assists in
      maintaining achievements of sustainable development. This applies to all sectors
      other than health, for instance, energy sectors, communication, transportation,
      education, production and agriculture. 

PMID- 25990975
TI  - Measuring the influence of industry sector membership on supply chain disruption
      reporting.
AB  - The global Supply Chain Resilience Survey by the Business Continuity Institute
      and Zurich Insurance is a comprehensive study on the state of supply chains in
      different organisations worldwide. As a benchmarking tool, it also contains data
      about business continuity arrangements in place to ensure supply chain
      resilience. Given this study's historically qualitative approach to reporting,
      this paper aims to introduce quantitative analysis. In this paper, responses that
      report membership in Standard Industrial Classification 2007 industry sectors
      from the 2013 Supply Chain Resilience Survey were disaggregated and related to
      supply chain disruption reporting. A chi-square test of independence reveals that
      membership in a particular industry sector influences reporting of supply chain
      disruption. Nonetheless, the relationship between these variables is weak. This
      study demonstrates interesting differences between industry sectors in terms of
      supply chain resilience. Further research is required in terms of other variables
      in order to provide granularity and relevant findings to supply chain planners. 

PMID- 25990976
TI  - Integrating business continuity, emergency preparedness and emergency response:
      How these seemingly different disciplines can come together to make a
      comprehensive integrated programme.
AB  - The East Bay Municipal Utility District provides potable water to approximately
      1.3 million customers and treats wastewater for approximately 680,000 customers
      on the eastern side of San Francisco Bay in Northern California. Corporate policy
      requires the District to create and maintain an active emergency preparedness
      programme to manage its critical functions during an emergency and protect
      people, property and the environment. The policy also requires the District to
      create and maintain a business continuity programme to minimise disruptions of
      critical business functions and enhance its capability to recover operations. For
      these programmes to work effectively they must be coordinated. As the programmes
      at the District have evolved, the natural interrelationship, overlaps and
      integration have become inherent in their success. To ensure integration and
      coordination of these programmes, the District has developed management systems
      to effectively drive towards a seamless overarching programme. 

PMID- 25990977
TI  - 'An abundance of caution' and Ebola in the US Healthcare System: What is the new
      normal?
AB  - Roosevelt General Hospital (RGH) is a small (24 bed) community hospital based in
      Portales, New Mexico, USA. RGH serves several towns and communities along the New
      Mexico/Texas border to include the enlisted and officer population of Cannon US
      Air Force Base as well as the civilian support and families for air force
      personnel. The area is also home to multiple retired and discharged military
      personnel who continue working in various roles as civilian contractors. As the
      care for the first US diagnosed patient with Ebola played out in neighbouring
      Texas (October 2014), a patient presented to the RGH clinic with a fever of
      unknown origin. Initially, there was a misunderstanding between the clinician and
      the patient regarding a recent international travel history. During the
      assessment, an ensuing discussion revealed that the patient had been in or near
      the area where the current West African Ebola outbreak is ongoing approximately
      10 days before the onset of his fever. While it was later determined that the
      patient was not infected with Ebola, the fact that a potentially infected patient
      had entered the hospital and had been in close contact with visitors and
      clinicians alike was disturbing to staff and administration. The continued
      operation of this hospital was and remains critical to the communities served.
      This story focuses on a local effort to manage a local concern relying on recent
      and historical emergency planning and preparedness efforts. 

PMID- 25990978
TI  - Intentional cargo disruption by nefarious means: Examining threats, systemic
      vulnerabilities and securitisation measures in complex global supply chains.
AB  - Global trade and commerce requires products to be securely contained and
      transferred in a timely way across great distances and between national
      boundaries. Throughout the process, cargo and containers are stored, handled and
      checked by a range of authorities and authorised agents. Intermodal
      transportation involves the use of container ships, planes, railway systems, land
      bridges, road networks and barges. This paper examines the the nefarious nature
      of intentional disruption and nefarious risks associated with the movement of
      cargo and container freight. The paper explores main threats, vulnerabilities and
      security measures relevant to significant intermodal transit risk issues such as
      theft, piracy, terrorism, contamination, counterfeiting and product tampering.
      Three risk and vulnerability models are examined and basic standards and
      regulations that are relevant to safe and secure transit of container goods
      across international supply networks are outlined. 

PMID- 25990979
TI  - The UK water crisis: What actions the government and private sector need to take.
AB  - The paper discusses why resilience is increasingly important for companies to
      measure and address, thinking about relevant issues such as climate change and
      extreme weather. It gives insight on how companies measure their resilience and
      that it is more than a business continuity issue; indeed, it is a board issue.
      The paper looks at the role of regulation for companies with national critical
      infrastructure in putting in resilience guidelines and discusses the benefits of
      regulation in resilience, presenting a case study of the UK Water Services
      Regulation Authority resilience guidelines. 

PMID- 25990980
TI  - Healthcare system resiliency: The case for taking disaster plans further - Part
      2.
AB  - For the most part, top management is aware of the costs of healthcare downtime.
      They recognise that minimising downtime while fulfilling risk management
      standards, namely, 'duty of care' and 'standard of care', are among the most
      difficult challenges they face, especially when coupled with the increasing
      pressure for continued service availability with the frequency of incidents.
      Through continuous operational availability and greater resiliency demands a new,
      combined approach has emerged, which necessitates that the disciplines of: (1)
      enterprise risk management; (2) emergency response planning; (3) business
      continuity management including IT disaster recovery; (4) crisis communications
      be addressed with strategies and techniques designed and integrated into a
      singular, seamless approach. It is no longer feasible to separate these
      disciplines. By integrating them as the gateway for service continuity, the
      organisation can enhance its ability to run as a business by helping to identify
      risks and prepare for change, prioritise work efforts, flag problems and pinpoint
      important areas that underpin the overarching business continuity processes. The
      driver of change in staying ahead of the risk curve, and the entry point of a
      true resiliency strategy, begins with identifying the synergies of the
      aforementioned disciplines and integrating each of them to jointly contribute to
      service continuance. 

PMID- 25990981
TI  - Stenting of Native Right Ventricular Outflow Tract Obstructions in Symptomatic
      Infants.
AB  - OBJECTIVE: To assess feasibility, safety and effectiveness of right ventricular
      outflow tract (RVOT) stenting in symptomatic young infants. METHODS: Multicentre
      evaluation of 35 patients intended to undergo RVOT stenting in 11 pediatric
      cardiac centres from 2009 to August 2011. RESULTS: Median age and weight at the
      time of first stent implantation were 8 weeks and 3.3 kg, with 40% of patients <3
      kg. A total of 19 patients had suffered from hypoxemic spells, 8 patients were
      ventilated, 6 on inotropic support and 5 on prostaglandin infusion. Severe
      concomitant malformations were present in 11 patients, and acute infections in 2.
      Stenting of the RVOT was successfully performed in 33 patients, improving oxygen
      saturation from a median of 77 to 90% 2 days after intervention. Besides the 2
      patients in whom RVOT stenting was not successful for technical reasons, there
      were no procedural complications. In 17 of 33 patients, 1-3 reinterventions were
      performed during follow-up, less than half of those were reinterventions in the
      RVOT. A total of 27 patients have undergone successful surgical repair 4-162
      (median 19.5) weeks after initial RVOT stent implantation, 2 patients are still
      waiting. There were no perioperative deaths. CONCLUSIONS: Stenting of the RVOT
      provides a safe and effective management strategy for initial palliation in
      symptomatic young infants, including those patients not suitable or at higher
      risk for surgical therapy.

PMID- 25990982
TI  - Azetidine- and N-carboxylic azetidine-iminosugars as amyloglucosidase inhibitors:
      synthesis, glycosidase inhibitory activity and molecular docking studies.
AB  - A simple strategy for the synthesis of hitherto unknown azetidine iminosugars 2a
      2c and N-carboxylic azetidine iminosugar 2d has been reported. The methodology
      involves the conversion of 1,2:5,6-di-O-isopropylidene-3-oxo-alpha-D
      glucofuranose 3 to 3-azido-3-deoxy-3-C-(formyl)-1,2:5,6-di-O-isopropylidene-alpha
      D-glucofuranose 5 using the Jocic-Reeve and Corey-Link approaches. Compound 5 was
      transformed to 5-OTs 10/5-OMs 19 derivatives that on intramolecular nucleophilic
      displacement with in situ generated 3-amino functionality afforded the key
      azetidine ring skeletons 11 and 20, respectively. Hydrolysis of the 1,2-acetonide
      group and manipulation of the anomeric carbon in 12 provided azetidine
      iminosugars 2a-2c. In an attempt to synthesize azetidine iminosugars with an
      additional 4-hydroxymethyl group from 20, we encountered an interesting
      observation wherein the N-Cbz group in 20 hydrolyzed to the N-COOH functionality
      under TFA:H2O conditions that gave access for the synthesis of N-carboxylic
      azetidine iminosugar 2d. The glycosidase inhibitory activity of 2a-2d and
      intermediates 2e-f was studied with various glycosidases and was compared with
      Miglitol and 1-deoxynojirimycin (DNJ). Azetidine iminosugars 2 were found to
      inhibit amyloglucosidase with competitive type inhibition, amongst which 2d was
      found to be more active than Miglitol and DNJ. These results were substantiated
      by in silico molecular docking studies.

PMID- 25990983
TI  - Development potential of e-waste recycling industry in China.
AB  - Waste electrical and electronic equipment (WEEE or e-waste) recycling industries
      in China have been through several phases from spontaneous informal family
      workshops to qualified enterprises with treatment fund. This study attempts to
      analyse the development potential of the e-waste recycling industry in China from
      the perspective of both time and scale potential. An estimation and forecast of e
      waste quantities in China shows that, the total e-waste amount reached
      approximately 5.5 million tonnes in 2013, with 83% of air conditioners,
      refrigerators, washing machines, televisions sand computers. The total quantity
      is expected to reach ca. 11.7 million tonnes in 2020 and 20 million tonnes in
      2040, which indicates a large increase potential. Moreover, the demand for
      recycling processing facilities, the optimal service radius of e-waste recycling
      enterprises and estimation of the profitability potential of the e-waste
      recycling industry were analysed. Results show that, based on the e-waste
      collection demand, e-waste recycling enterprises therefore have a huge
      development potential in terms of both quantity and processing capacity, with 144
      and 167 e-waste recycling facilities needed, respectively, by 2020 and 2040. In
      the case that e-waste recycling enterprises set up their own collection points to
      reduce the collection cost, the optimal collection service radius is estimated to
      be in the range of 173 km to 239 km. With an e-waste treatment fund subsidy, the
      e-waste recycling industry has a small economic profit, for example ca.
      US$2.5/unit for television. The annual profit for the e-waste recycling industry
      overall was about 90 million dollars in 2013.

PMID- 25990984
TI  - Urinary enterolactone associated with liver enzyme levels in US adults: National
      Health and Nutrition Examination Survey (NHANES).
AB  - Phyto-oestrogens are a family of plant-derived xeno-oestrogens that appear to
      have beneficial effects on human health. To date, no data are available about
      phyto-oestrogen consumption affecting liver health in a population. The present
      study aimed to explore the relationship of urinary phyto-oestrogen metabolites
      with serum liver enzymes in US adults. A nationally representative sample of US
      adults in the National Health and Nutrition Examination Survey (NHANES) 2003-10
      was analysed. The cross-sectional study sample consisted of 6438 adults with data
      on urinary phyto-oestrogen levels, serum alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl
      transaminase (GGT) concentrations and data on other potential confounders.
      Multivariate logistic regression and linear regression were applied to assess
      associations between urinary phyto-oestrogen levels and ALT, AST, ALP and GGT
      concentrations. We found a remarkable association between urinary enterolactone
      and GGT in both adult males (OR 0.37, 95 % CI 0.22, 0.61; P= 0.003) and females
      (OR 0.37, 95 % CI 0.26, 0.54; P= 0.009). Moreover, elevated enterolactone levels
      were inversely associated with ALT and AST levels in adult males. However, no
      association was present between levels of urinary daidzein, O
      desmethylangolensin, equol, enterodiol or genistein with liver enzyme levels in
      this population. The present study results provide epidemiological evidence that
      urinary enterolactone levels are associated with liver GGT levels in humans. This
      suggests a potential protective effect of enterolactone on human liver function.
      However, the underlying mechanisms still need further investigation.

PMID- 25990985
TI  - A Refined Single-Particle Reconstruction Procedure to Process Two-Dimensional
      Crystal Images from Transmission Electron Microscopy.
AB  - Single-particle reconstruction (SPR) and electron crystallography (EC), two major
      applications in electron microscopy, can be used to determine the structure of
      membrane proteins. The three-dimensional (3D) map is obtained from separated
      particles in conventional SPR, but from periodic unit cells in EC. Here, we
      report a refined SPR procedure for processing 2D crystal images. The method is
      applied to 2D crystals of melibiose permease, a secondary transporter in
      Escherichia coli. The current procedure is improved from our previously published
      one in several aspects. The "gold standard Fourier shell correlation" resolution
      of our final reconstruction reaches 13 A, which is significantly better than the
      previously obtained 17 A resolution. The choices of different refinement
      parameters for reconstruction are discussed. Our refined SPR procedure could be
      applied to determine the structure of other membrane proteins in small or locally
      distorted 2D crystals, which are not ideal for EC. 

PMID- 25990986
TI  - Trajectories of Scores on a Screening Instrument for PTSD Among World Trade
      Center Rescue, Recovery, and Clean-Up Workers.
AB  - The longitudinal course of posttraumatic stress disorder (PTSD) over 8-9 years
      was examined among 16,488 rescue and recovery workers who responded to the events
      of September 11, 2001 (9/11) at the World Trade Center (WTC; New York, NY), and
      were enrolled in the World Trade Center Health Registry. Latent class growth
      analysis identified 5 groups of rescue and recovery workers with similar score
      trajectories at 3 administrations of the PTSD Checklist (PCL): low-stable
      (53.3%), moderate- stable (28.7%), moderate-increasing (6.4%), high-decreasing
      (7.7%), and high-stable (4.0%). Relative to the low-stable group, membership in
      higher risk groups was associated with 9/11-related exposures including duration
      of WTC work, with adjusted odds ratios ranging from 1.3 to 2.0, witnessing of
      horrific events (range = 1.3 to 2.1), being injured (range = 1.4 to 2.3),
      perceiving threat to life or safety (range = 2.2 to 5.2), bereavement (range =
      1.6 to 4.8), and job loss due to 9/11 (range = 2.4 to 15.8). Within groups,
      higher PCL scores were associated with adverse social circumstances including
      lower social support, with B coefficients ranging from 0.2 to 0.6, divorce,
      separation, or widowhood (range = 0.4-0.7), and unemployment (range = 0.4-0.5).
      Given baseline, exposure-related, and contextual influences that affect divergent
      PTSD trajectories, screening for both PTSD and adverse circumstances should occur
      immediately, and at regular intervals postdisaster. 

PMID- 25990987
TI  - A Practical ECG Criterion to Unmask Left Accessory AV Connections in Patients
      With Subtle Preexcitation.
AB  - BACKGROUND: Accessory AV-connections capable of antegrade conduction need to be
      recognized because of the potential for life-threatening arrhythmias. However,
      the preexcited ECG pattern may be subtle, especially among left-sided AV
      connections. We explored whether additional ECG criteria might help identify left
      sided AV-connections. METHODS: We analyzed 156 patients who underwent an
      electrophysiology study (EPS) and ablation for paroxysmal supraventricular
      tachycardias (PSVT). Patients were divided into 2 groups: those with left-sided
      AV-connections (Group 1) and all other PSVT (Group 2). Various ECG parameters
      were compared before and after ablation in both groups. RESULTS: The EPS
      identified left-sided AV-connections among 43 patients (Group 1) and excluded it
      among 113 (Group 2). Baseline ECG in Group 1 demonstrated obvious preexcitation
      among 24/43 patients (55.8%), the remaining 19/43 missing obvious preexcitation.
      R/S ratio > 0.5 in V1 was noted in 38/43 (88.4%) patients in Group 1 before
      ablation (median 1.00; IQR 0.58-2.20), including 16/19 (84.2%) patients lacking
      obvious left-sided AVconnections. Conversely, only 10/113 (8.8%) patients in
      Group 2 had R/S ratios in V1 >= 0.5 (0.20; 0.10-0.31), P < 0.0001. After
      ablation, the R/S ratio decreased significantly in Group 1 (0.29; 0.17-0.45), P <
      0.0001. Thus, a combined criterion of classic preexcitation or R/S ratio >= 0.5
      on ECG identified 40/43 left-sided AV-connections (sensitivity 93.0%). The
      negative predictive value of this combined criterion was 103/106 (97.2%).
      CONCLUSIONS: In symptomatic patients, combining the R/S ratio (>= 0.5) in lead V1
      with the classic preexcitation pattern on ECG markedly improved the sensitivity
      to diagnose left-sided AV-connections. This ratio may be particularly useful
      among patients lacking obvious preexcitation.

PMID- 25990988
TI  - Pang-Rotenberg sign--snoring surgery prognosticator: A prospective clinical trial
      of 153 patients.
AB  - OBJECTIVES/HYPOTHESIS: To illustrate the reliability of the Pang-Rotenberg (PR)
      sign as a prognosticator of snoring surgery. Our hypothesis was that patients who
      are PR-positive have better snoring reduction scores and outcomes than PR
      negative patients after nose and palate surgery. STUDY DESIGN: A multicenter
      prospective series of 153 patients with snoring. METHODS: All patients graded the
      snoring intensity on a visual analog scale (VAS). All 137 patients enrolled had
      both the nose surgery and palate surgery. The control group consisted of 16
      patients who underwent nasal surgery alone. RESULTS: There were 122 men and 15
      women, the mean age was 44.6 years old, and mean body mass index was 26.1. There
      were 15 simple snorers and 122 obstructive sleep apnea patients. Patients who
      were PR-positive showed significantly better postoperative snoring VAS reduction
      (from 9.04 to 1.02) compared to those patients who were PR-negative (from 8.91 to
      3.14) (P < .001). The mean follow-up time was 7.4 months. The control group had
      poor snoring VAS reduction from 9.21 to 6.72. After adjusting for covariates that
      influence the snoring VAS change due to surgery, we found that PR-negative
      patients achieved an average of 5.78 improvement in snoring VAS, whereas PR
      positive patients achieved an average of 8.02 improvement in snoring VAS (P <
      .001). CONCLUSIONS: The PR sign is a reliable prognosticator of snoring
      reduction, after combined nose and palate surgery, for patients with troublesome
      snoring.

PMID- 25990989
TI  - Maurice lev, MD november 13, 1908 to february 4, 1994.

PMID- 25990990
TI  - Physical and chemical injury as causes of sudden cardiac death: the forensic
      forum.
AB  - Physical and chemical injuries account for the largest number of sudden,
      unexpected cardiac deaths in persons between the ages of 1 and 44 years. Blunt
      force injuries, lacerations, avulsions, and contusions of the heart and great
      vessels sustained during motor vehicle crashes constitute the most prevalent type
      of lethal physical trauma to the cardiovascular system. The second most prevalent
      type of trauma is from penetrating and perforating wounds inflicted by firearms.
      The mechanisms of these injuries are discussed, with emphasis placed on those
      factors contributing to lethality. The three most prevalent chemicals associated
      with sudden cardiac death-ethyl alcohol, cocaine, and tricylic antidepressants
      are briefly mentioned. 

PMID- 25990991
TI  - Surgical pathology of the aortic valve: gross and histological findings in 1120
      excised valves.
AB  - From January 1981 through December 1991, 1120 consecutive aortic valves were
      surgically explanted and their gross anatomy and histology studied at our
      university. Rheumatic disease (65%), dystrophic calcific valvular disease (23%),
      noninflammatory disease of the aortic root and/or floppy aortic valve (6.3%), and
      endocarditis (5.4%) were the causes of valve dysfunction. Among the total
      population the male sex predominated. The male to female ratio was 2.4 in the
      group with dystrophic calcific valvular disease and 1.6 in the group with
      bacterial endocarditis. The mean age was 37 +/- 7.5 years in the group with non
      inflammatory disease of the aortic root and/or aortic cusps. In the group with
      dystrophic calcific valvular disease, the mean age was 62 +/- 6.3 years. Among
      the 1120 patients, 717 (64.03%) underwent surgery for aortic stenotic
      incompetence, 250 (22.25%) for isolated aortic stenosis, and 153 (13.72%) for
      isolated aortic incompetence. In 449 cases (40.13%) a mitral pathology was
      associated. Chronic rheumatic aortic disease usually caused stenotic
      insufficiency (92.8%). Dystrophic calcific aortic disease caused pure stenosis in
      84.8% of the cases. Among these, 46 patients (18.4%) had a congenitally
      bicuspidal aortic valve. Pure aortic incompetence was caused by noninflammatory
      aortic root and/or cusp disease in 44% of patients, infective endocarditis in
      40%, and rheumatic disease in 16%. Patients with noninflammatory aortic root
      and/or cusp disease were divided into three groups: 29 patients with aortic root
      dilatation and normal cusps, 25 patients with aortic root dilatation and
      mixomatous infiltration of aortic cusps (floppy aortic valve), and 15 patients
      with floppy aortic valve and normal aortic root. Aortic incompetence was caused
      by cusp retraction caused by chronic rheumatic disease, cusp perforation or tears
      caused by infective endocarditis, and cusp prolapse for floppy aortic valve. Cusp
      diastasis has been the cause of aortic incompetence in patients with dilated
      aortic root. In patient with floppy aortic valve caused by the fibrous lamina
      disarray, the cusps prolapsed toward the left ventricle, causing valve
      regurgitation. 

PMID- 25990992
TI  - Mucoid degeneration of the atrioventricular valve caused by cardiac lymphostasis:
      An experimental study in dogs.
AB  - We performed an experiment to examine the influence of cardiac lymph congestion
      on the cardiac valves in dogs. A total of 6 mongrel dogs underwent surgery to
      induce cardiac lymph congestion, and 6 other animals underwent sham operation.
      Two weeks after operation, the atrioventricular valves of the experimental
      animals were intensively stained by Alcian blue. The optical densities of the
      tricuspid valves measured by a microscopic photometer were 0.069 +/- 0.033 in the
      proximal portion, 0.134 +/- 0.030 in the middle portion, and 0.117 +/- 0.023 in
      the peripheral portion. All corresponding values obtained from the sham-operated
      animals showed lower values of 0.048 +/- 0.012, 0.046 +/- 0.014 (p < 0.05), and
      0.060 +/- 0.028 (p < 0.01), respectively. Electron microscopic observation
      revealed dilatation of the lymphatic vessels in the experimental valves. The
      results suggest that cardiac lymph congestion causes accumulation of
      mucopolysaccharides in the valve. 

PMID- 25990993
TI  - Correlation between endomyocardial biopsies and ventricle full-thickness samples
      in dilated cardiomyopathy: A study of myocytes and fibrosis.
AB  - Eight patients with end-stage dilated cardiomyopathy were studied. Right
      ventricular endomyocardial biopsy morphometric findings were correlated with
      those of full-thickness samples of the right ventricle and interventricular
      septum obtained from the hearts of the same patients at cardiac transplant. The
      percentage area of myocytes and fibrosis was measured on histologic sections by
      means of a quantitative method. The results showed a close correlation between
      fibrosis and myocytes of biopsies and those of subendocardial, subepicardial, and
      midwall layers of the right ventricle free wall. No correlation was found with
      the subendocardial layers or with the midwall of the interventricular septum.
      These data suggest that histologic features of biopsies taken from the right
      ventricle from patients with dilated cardiomyopathy resemble those of the right
      ventricle free wall only. 

PMID- 25990994
TI  - Immediate causes of death in short-term surviving heart transplant recipients.
AB  - From 1985 to 1992, 1068 cardiac transplants have been performed in the Italian
      units. The immediate causes of death of 142 of the 148 orthotopic cardiac
      transplantation recipients who died within the first 6 postoperative months were
      surveyed. Deaths were grouped into three periods: perioperative (?1 month,
      68.3%), early (>1 ?3 months, 23.2%), and advanced (>3 ?6 months, 8.5%). Acute
      graft failure (arising from the ischemic damage to the donor heart, from surgical
      problems, from severe pulmonary hypertension, or from multiorgan failure)
      accounted for 49% of perioperative deaths and, along with noncardiac emergencies
      (23% of perioperative deaths), was significantly more frequent in this period
      than in the subsequent ones. The dissection of thoracic arteries was responsible
      for 4% of postoperative deaths, occurring exclusively among patients transplanted
      for ischemic or valvular heart disease. In the early and advanced periods,
      untreatable acute rejection (13%) and fatal infections (38%), mostly saprophytic,
      were significantly more frequent. Ischemic heart damage secondary to graft
      vasculopathy already caused 26% of deaths between the fourth and sixth months
      after transplantation. Some diseases, such as acute rejection, had the same
      frequency as both underlying disease and immediate cause of death. On the
      contrary, graft failure is more common as primary disease, leading to death also
      through noncardiac complications and saprophytic infections. Bacterial infections
      have the same frequency as both prime and immediate cause of death, viral
      infections are more common as primary disease, and the opposite is true for
      saprophytic infections. 

PMID- 25990995
TI  - Muramidase: A useful monocyte/macrophage immunocytochemical marker in swine, of
      special interest in experimental cardiovascular disease.
AB  - The reliability of a rabbit polyclonal antibody against muramidase to identify
      monocytes/macrophages in swine was evaluated by immunostaining of cell smears and
      formaldehyde-fixed, paraffin-embedded tissue sections. Blood in tissue sections,
      cell smears (peripheral blood, buffy coat, and isolated mononuclear cells), and
      cultured mononuclear cells (adherent monocytes) contained positively stained
      cells with a morphology and in a number corresponding to that expected for a
      monocyte marker. Polymorphonuclear leukocytes (PMN), lymphocytes, and platelets
      were negative. In normal organs and tissues, mesenchymal cells with a
      distribution similar to that expected for macrophages were found to stain
      positively for muramidase. In pathologic tissues, positively stained inflammatory
      cells were identified in wounds, infected lungs, recently infarcted myocardium,
      and acute (variable numbers), organizing (often many), and healed (usually few)
      arterial thrombi. Enzymatic unmasking of antigenic determinants by trypsinization
      was necessary to achieve strong and consistent staining of monocytes/macrophages
      in tissue sections. A variety of epithelial cells of no differential diagnostic
      significance for monocyte/macrophage identification (e.g., renal proximal tubular
      cells) also stained positive for muramidase. The staining pattern of muramidase
      in swine corresponds to that described in humans, in whom muramidase has been
      shown to be a valuable marker of monocytes/macrophages. Swine PMN were, however,
      not stained or only weakly stained, whereas human PMN reportedly are strongly
      positive. As in humans, swine cardiac myocytes, smooth muscle cells, endothelial
      cells, lymphocytes, and platelets were consistently negative. This antibody
      against muramidase is a useful immunohistochemical marker for swine
      monocytes/macrophages in formaldehyde-fixed, paraffin-embedded tissues. 

PMID- 25990996
TI  - Classification and histopathologic specificity of systemic vasculitis.

PMID- 25990997
TI  - Systemic necrotizing vasculitis.
AB  - Systemic necrotizing vasculitis may be idiopathic or associated with a variety of
      diseases of known etiology. A typical example is polyarteritis nodosa, which is
      characterized by fibrinoid necrosis and severe inflammation leading to
      destruction of the wall, narrowing of the lumen, and interference with blood
      circulation. In addition to the idiopathic form, histologically similar lesions
      are seen in hepatitis B, rheumatoid arthritis, Kawasaki mucocutaneous lymph node
      syndrome, and other diseases. Microscopic polyangitis involves mainly small
      vessels-venules more often than arterioles-but occasionally also small arteries.
      Its characteristic feature is leukocytoclasia of neutrophilic leukocytes, but
      fibrinoid necrosis also occurs. Churg-Strauss syndrome consists of granulomas in
      patients with a background of severe allergy, such as asthma, allergic rhinitis,
      or occasionally drug sensitization. 

PMID- 25990998
TI  - Pathologic features of aortitis.

PMID- 25990999
TI  - Common and uncommon manifestations of wegener's granulomatosis.

PMID- 25991000
TI  - Occidental (temporal) and oriental (takayasu) giant cell arteritis.

PMID- 25991002
TI  - Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From
      Trastuzumab in Breast Cancer.
AB  - BACKGROUND: Studies have shown that antibodies targeting the intracellular (ICD)
      or extracellular domains (ECD) of human epidermal growth factor receptor 2 (HER2)
      are equivalent when traditional methods are used. We describe a new method to
      quantify ICD and ECD expression separately and assess the prognostic value of
      domain-specific HER2 results in patients who received adjuvant trastuzumab
      therapy. METHODS: We measured HER2 protein expression with quantitative
      immunofluorescence (QIF) in tissue microarrays (TMA) using two different
      antibodies targeting the ICD (CB11 and A0485) and ECD (SP3 and D8F12). We
      assessed the prognostic value of ICD and ECD expression in 180 patients from a
      clinical trial of adjuvant chemotherapy followed by trastuzumab (HeCOG 10/05). We
      performed an exploratory univariate domain-specific, disease-free survival (DFS)
      analysis and compared DFS functions with Kaplan-Meier estimates. All statistical
      tests were two-sided. RESULTS: HER2 ICD expression by QIF showed slightly higher
      sensitivity to predict ERBB2 (HER2) gene amplification than ECD expression, which
      was more specific and had higher positive predictive value. In the HeCOG 10/05
      trial specimens, 15% of cases showed discordant results for ICD and ECD
      expression. High ECD was statistically associated with longer DFS (log-rank P =
      .049, HR = 0.31, 95% CI = 0.144 to 0.997), while ICD status was not. Among
      patients with low ECD, there was no difference in DFS by ICD status. However,
      when ICD was high, high ECD was statistically associated with longer DFS (log
      rank P = .027, HR = 0.23, 95% CI = 0.037 to 0.82) compared with low ECD.
      CONCLUSION: Quantitative measurements of HER2 ICD and ECD expression in breast
      cancer suggest a subclassification of HER2-positive tumors. Trastuzumab-treated
      patients with high ECD showed better DFS than patients with low ECD. This
      suggests differential benefit from trastuzumab therapy based on HER2 ECD
      expression.

PMID- 25991003
TI  - Electronic medical record-based multicondition models to predict the risk of 30
      day readmission or death among adult medicine patients: validation and comparison
      to existing models.
AB  - BACKGROUND: There is increasing interest in using prediction models to identify
      patients at risk of readmission or death after hospital discharge, but existing
      models have significant limitations. Electronic medical record (EMR) based models
      that can be used to predict risk on multiple disease conditions among a wide
      range of patient demographics early in the hospitalization are needed. The
      objective of this study was to evaluate the degree to which EMR-based risk models
      for 30-day readmission or mortality accurately identify high risk patients and to
      compare these models with published claims-based models. METHODS: Data were
      analyzed from all consecutive adult patients admitted to internal medicine
      services at 7 large hospitals belonging to 3 health systems in Dallas/Fort Worth
      between November 2009 and October 2010 and split randomly into derivation and
      validation cohorts. Performance of the model was evaluated against the Canadian
      LACE mortality or readmission model and the Centers for Medicare and Medicaid
      Services (CMS) Hospital Wide Readmission model. RESULTS: Among the 39,604 adults
      hospitalized for a broad range of medical reasons, 2.8% of patients died, 12.7%
      were readmitted, and 14.7% were readmitted or died within 30 days after
      discharge. The electronic multicondition models for the composite outcome of 30
      day mortality or readmission had good discrimination using data available within
      24 h of admission (C statistic 0.69; 95% CI, 0.68-0.70), or at discharge (0.71;
      95% CI, 0.70-0.72), and were significantly better than the LACE model (0.65; 95%
      CI, 0.64-0.66; P =0.02) with significant NRI (0.16) and IDI (0.039, 95% CI, 0.035
      0.044). The electronic multicondition model for 30-day readmission alone had good
      discrimination using data available within 24 h of admission (C statistic 0.66;
      95% CI, 0.65-0.67) or at discharge (0.68; 95% CI, 0.67-0.69), and performed
      significantly better than the CMS model (0.61; 95% CI, 0.59-0.62; P < 0.01) with
      significant NRI (0.20) and IDI (0.037, 95% CI, 0.033-0.041). CONCLUSIONS: A new
      electronic multicondition model based on information derived from the EMR
      predicted mortality and readmission at 30 days, and was superior to previously
      published claims-based models.

PMID- 25991004
TI  - affy2sv: an R package to pre-process Affymetrix CytoScan HD and 750K arrays for
      SNP, CNV, inversion and mosaicism calling.
AB  - BACKGROUND: The well-known Genome-Wide Association Studies (GWAS) had led to many
      scientific discoveries using SNP data. Even so, they were not able to explain the
      full heritability of complex diseases. Now, other structural variants like copy
      number variants or DNA inversions, either germ-line or in mosaicism events, are
      being studies. We present the R package affy2sv to pre-process Affymetrix
      CytoScan HD/750k array (also for Genome-Wide SNP 5.0/6.0 and Axiom) in structural
      variant studies. RESULTS: We illustrate the capabilities of affy2sv using two
      different complete pipelines on real data. The first one performing a GWAS and a
      mosaic alterations detection study, and the other detecting CNVs and performing
      an inversion calling. CONCLUSION: Both examples presented in the article show up
      how affy2sv can be used as part of more complex pipelines aimed to analyze
      Affymetrix SNP arrays data in genetic association studies, where different types
      of structural variants are considered.

PMID- 25991005
TI  - Combined percutaneous and transarterial devascularisation of juvenile
      nasopharyngeal angiofibroma with protection of internal carotid artery: A
      modification of the technique.
AB  - Juvenile nasal angiofibroma (JNA) is a hypervascularised, benign, but locally
      aggressive tumour that grows in the posterior, upper part of the nasal cavity and
      invades surrounding anatomical structures. The treatment of choice is surgical
      removal, but complete resection of the tumour can be hampered because of profuse
      perioperative bleeding. Preoperative embolisation of the tumour has been proposed
      as an effective method for prevention of perioperative bleeding, thereby
      shortening of the time of the operation. In this report of five cases, we
      describe successful preoperative devascularisation of the tumour by applying a
      modified method of direct intratumoural injection of the liquid embolic agent
      Onyx combined with protection of the internal carotid artery. The control of
      bleeding during the embolisation and occlusion of the maxillary or sphenopalatine
      artery was achieved by using a bi-luminal balloon catheter. Such use of the dual
      lumen catheter in treatment of JNA has not been reported so far in the medical
      literature. 

PMID- 25991006
TI  - Not all women with dense breasts need further imaging after normal mammogram,
      study shows.

PMID- 25991007
TI  - A panel of eight-miRNA signature as a potential biomarker for predicting survival
      in bladder cancer.
AB  - BACKGROUND: There is increasing evidence to suggest that miRNAs play an important
      role in predicting cancer survival. To identify a panel of miRNA signature that
      can divided tumor from normal bladder using miRNA expression levels, and to
      assess the prognostic value of this specific miRNA markers in bladder cancer
      (BCa). METHODS: A comprehensive meta-review of published miRNA expression
      profiles that compared BCa and adjacent normal tissues was performed to determine
      candidate miRNAs as prognostic biomarkers for BCa. Vote-counting strategy and
      Robust Rank Aggregation method were used to identify significant meta-signature
      miRNAs. RESULTS: We identified an eight-miRNA signature including three
      upregulated (miR-141, miR-200c, miR-21) and five downregulated (miR-145, miR-125,
      miR-199a, let-7c and miR-99a) miRNAs for the prediction of overall survival (OS)
      using TCGA dataset, and validated in our 48 BCa patients. X-tile plot was used to
      generate the optimum cut-off point and Kaplan-Meier method was used to calculate
      OS. A linear prognostic model of eight miRNAs was constructed and weighted by the
      importance scores from the supervised principal component method to divide
      patients into high- and low-risk groups. Patients assigned to the high-risk group
      were associated with poor OS compared with patients in the low-risk group (HR =
      5.21, p < 0.001). Our validation cohort of 48 patients confirmed the panel of 8
      miRNAs as a reliable prognostic tool for OS in patients with BCa (HR = 5.04, p <
      0.001). CONCLUSION: The present meta-analysis identified eight highly significant
      and consistently dysregulated miRNAs from 19 datasets. We also constructed an
      eight-miRNA signature which provided predictive and prognostic value that
      complements traditional clinicopathological risk factors.

PMID- 25991008
TI  - Migraine-specific quality of life questionnaire and relapse of medication overuse
      headache.
AB  - BACKGROUND: The management of Medication overuse headache (MOH) represents a
      difficult challenge for clinicians and headache experts, particularly for the
      responder rate after a successful withdrawal treatment. The purpose of this study
      was to investigate the role of demographic and clinical characteristics as well
      as the score of Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine
      Disability Questionnaire and Leeds Dependence Questionnaire in predicting a
      response after a successful withdrawal treatment in patients with MOH. METHODS:
      This ancillary study is part of a randomized trial that demonstrated the safety
      and the efficacy of a 3-month treatment with sodium valproate (VPA) (800 mg/day
      vs placebo) in MOH. Demographic and clinical characteristics and questionnaire
      results were obtained from the entire sample. RESULTS: A significant correlation
      was found only between MOH relapse and the total MSQ score, the Role Preventive
      sub-scale and the Emotional Function sub-scale, suggesting a poorer quality of
      life in non responders. CONCLUSION: A high MSQ score could be associated with a
      poor short-term outcome in MOH patients after a successful treatment with
      detoxification followed by a new treatment.

PMID- 25991009
TI  - Spinal motor-evoked potentials vs. 50-Hz artifact: Reply.

PMID- 25991010
TI  - Minimally invasive aortic valve replacement: Comparison of long-term outcomes.
AB  - BACKGROUND: Minimally invasive aortic valve replacement tends to be performed in
      specialist centers. Little data exists with regard to long-term outcomes of the
      upper hemi-sternotomy technique. We sought to evaluate the short- and long-term
      outcomes of this procedure in our institution. METHODS: Data were collected from
      our cardiac surgical database. We compared the outcomes of all patients who
      underwent minimally invasive aortic valve replacement with all who underwent
      conventional aortic valve replacement between July 1999 and December 2013.
      Propensity-matching analysis was performed to evaluate hospital outcomes.
      RESULTS: There were 125 patients who underwent minimally invasive aortic valve
      replacement and 1446 who had conventional surgery. After propensity score
      matching, there were no differences in postoperative mortality or complications
      between the 2 groups. The only significant differences were longer bypass (62.69
      +/- 10.12 vs. 68.94 +/- 14.79 min, p = 0.002) and crossclamp times (45.48 +/-
      8.08 vs. 52.30 +/- 16.29 min, p < 0.001) in conventional surgery. Long-term
      survival after minimally invasive aortic valve replacement at 2, 6, and 10 years
      was 88% +/- 3.0%, 79% +/- 4.0%, and 66% +/- 6.0%, respectively. Predictors of
      long-term survival were age, peripheral vascular disease, and low ejection
      fraction (p < 0.005). CONCLUSION: Minimally invasive aortic valve replacement has
      similar hospital outcomes compared to conventional aortic valve replacement. The
      operation is quicker and does not confer any significant increase in
      complications or length of hospital stay. The long-term outcomes are favorable
      and justify its continued use by specialist surgeons in the United Kingdom.

PMID- 25991011
TI  - Standardized Outcome Measurement for Patients With Coronary Artery Disease:
      Consensus From the International Consortium for Health Outcomes Measurement
      (ICHOM).
AB  - BACKGROUND: Coronary artery disease (CAD) outcomes consistently improve when they
      are routinely measured and provided back to physicians and hospitals. However,
      few centers around the world systematically track outcomes, and no global
      standards exist. Furthermore, patient-centered outcomes and longitudinal outcomes
      are under-represented in current assessments. METHODS AND RESULTS: The nonprofit
      International Consortium for Health Outcomes Measurement (ICHOM) convened an
      international Working Group to define a consensus standard set of outcome
      measures and risk factors for tracking, comparing, and improving the outcomes of
      CAD care. Members were drawn from 4 continents and 6 countries. Using a modified
      Delphi method, the ICHOM Working Group defined who should be tracked, what should
      be measured, and when such measurements should be performed. The ICHOM CAD
      consensus measures were designed to be relevant for all patients diagnosed with
      CAD, including those with acute myocardial infarction, angina, and asymptomatic
      CAD. Thirteen specific outcomes were chosen, including acute complications
      occurring within 30 days of acute myocardial infarction, coronary artery bypass
      grafting surgery, or percutaneous coronary intervention; and longitudinal
      outcomes for up to 5 years for patient-reported health status (Seattle Angina
      Questionnaire [SAQ-7], elements of Rose Dyspnea Score, and Patient Health
      Questionnaire [PHQ-2]), cardiovascular hospital admissions, cardiovascular
      procedures, renal failure, and mortality. Baseline demographic, cardiovascular
      disease, and comorbidity information is included to improve the interpretability
      of comparisons. CONCLUSIONS: ICHOM recommends that this set of outcomes and other
      patient information be measured for all patients with CAD.

PMID- 25991012
TI  - Selective Serotonin Reuptake Inhibitors (SSRIs) and the Risk of Congenital Heart
      Defects: A Meta-Analysis of Prospective Cohort Studies.
AB  - BACKGROUND: Recent studies have reported conflicting results on the association
      between selective serotonin reuptake inhibitors (SSRIs) and the risk of heart
      defects. We aimed to assess the association between SSRIs in pregnant women
      during the first trimester and the risk of congenital heart defects. METHODS AND
      RESULTS: PubMed and EMBASE up to July 2014 were searched for population-based
      cohort studies that reported SSRIs in pregnant women during the first trimester
      and live infants' heart defects at follow-up. A meta-analysis of published data
      was undertaken primarily by means of fixed-effects models. Four cohort studies
      including 1 996 519 participants were included with a mean follow-up period
      ranging from discharge to 72 months. SSRIs were not associated with increased
      risks of heart defects 1.06 (95% confidence interval: 0.94 to 1.18). CONCLUSIONS:
      SSRIs during the first trimester in pregnant women were not associated with
      increased risks for newborn heart defects.

PMID- 25991014
TI  - US physicians' group releases guidelines for "high value" cancer screening.

PMID- 25991013
TI  - Coronary Wall Structural Changes in Patients With Kawasaki Disease: New Insights
      From Optical Coherence Tomography (OCT).
AB  - BACKGROUND: Coronary artery aneurysms (CAA) are serious complications of Kawasaki
      disease (KD). Optical coherence tomography (OCT) is a high-resolution
      intracoronary imaging modality that characterizes coronary artery wall structure.
      The purpose of this work was to describe CAA wall sequelae after KD. METHODS AND
      RESULTS: KD patients scheduled for routine coronary angiography underwent OCT
      imaging between March 2013 and August 2014. Subjects' clinical courses,
      echocardiography, and coronary angiography examinations were reviewed
      retrospectively. OCT was performed in 18 patients aged 12.4+/-5.5 years, 9.0+/
      5.1 years following onset of KD. Of those, 14 patients (77.7%) had a history of
      CAA (7 with giant CAA and 7 with regressed CAA at time of OCT). Intracoronary
      nitroglycerin was given to all patients (88.4+/-45.5 MUg/m(2)). Mean radiation
      dose was 10.9+/-5.2 mGy/kg. One patient suffered from a transitory uneventful
      vasospasm at the site of a regressed CAA; otherwise no major procedural
      complications occurred. The most frequent abnormality observed on OCT was intimal
      hyperplasia (15 patients, 83.3%) seen at both aneurysmal sites and
      angiographically normal segments amounting to 390.8+/-166.0 MUm for affected
      segments compared to 61.7+/-17 MUm for unaffected segments (P<0.001).
      Disappearance of the media, and presence of fibrosis, calcifications, macrophage
      accumulation, neovascularization, and white thrombi were seen in 72.2%, 77.8%,
      27.8%, 44.4%, and 33.3% of patients. CONCLUSIONS: In this study, OCT proved safe
      and insightful in the setting of KD, with the potential to add diagnostic value
      in the assessment of coronary abnormalities in KD. The depicted coronary
      structural changes correspond to histological findings previously described in
      KD.

PMID- 25991016
TI  - A Portuguese version of the student-teacher relationship scale - short form.
AB  - Research consistently demonstrates that positive student-teacher relationships
      are fundamental to the healthy development of all students. However, we lack a
      Portuguese-validated measure of student-teacher relationships. In this article we
      present the adaptation procedures and the psychometric properties of a Portuguese
      version of the Student-Teacher Relationship Scale - Short Form (Pianta, 1992).
      Five hundred and thirty five teachers from 127 schools completed the STRS-SF. The
      results demonstrate that this adapted version of the STRS-SF has good
      psychometric properties, namely high reliability (alpha = .84 to .87) and
      expected construct validity, which were tested through exploratory and
      confirmatory factor analyses (chi2/df = 1.65, CFI = .96, GFI = .93, RMSEA =
      0.05). This study also showed that the correlations of student-teacher
      relationship with students' demographic variables are consistent with the
      evidence in the literature about this construct. Finally, the study indicated
      that female teachers reported more closeness, t(530) = 4.06, p < .001 and better
      overall student-teacher relationships, t(530) = 4.90, p < .001. In the
      discussion, we analyze the implications of these results. 

PMID- 25991015
TI  - Altered profile of serum microRNAs in pancreatic cancer-associated new-onset
      diabetes mellitus.
AB  - BACKGROUND: New-onset diabetes mellitus in pancreatic cancer has been recognized
      as a paraneoplastic phenomenon caused by the existence of the tumor. Circulating
      microRNAs (miRNAs) are emerging as non-invasive biomarkers for the detection of
      various cancers. In the present study, we hypothesized that a specific serum
      miRNA profile exists in pancreatic cancer-associated new-onset diabetes mellitus
      (PaC-DM). METHODS: Initial screening of differentially expressed miRNAs in pooled
      serum samples from 25 PaC-DM patients, 25 non-cancer new-onset type 2 diabetes
      mellitus (T2DM) patients, and 25 healthy controls was performed by TaqMan low
      density arrays (TLDA). A stem-loop quantitative reverse transcription-polymerase
      chain reaction (qRT-PCR) was conducted to confirm the relative concentrations of
      candidate miRNAs in 80 PaC-DM, 85 non-cancer new-onset T2DM patients, and 80
      healthy controls. RESULTS: The TLDA identified 16 serum miRNAs that were
      significantly increased in PaC-DM samples. A combination of six serum miRNAs (miR
      483-5p, miR-19a, miR-29a, miR-20a, miR-24, miR-25) was selected by qRT-PCR as a
      biomarker for PaC-DM. The area under the receiver operating characteristic curve
      (AUC) for the six-miRNA panel training and validation sets was 0.959 (95%
      confidence interval [CI] 0.890-1.028) and 0.902 (95% CI 0.844-0.955),
      respectively. The combination of these six miRNAs enabled the discrimination of
      PaC-DM from non-cancer new-onset T2DM with an AUC of 0.885 (95% CI 0.784-0.986)
      and 0.887 (95% CI 0.823-0.952) for the training and validation sets,
      respectively. CONCLUSION: The six-serum miRNA panel may have potential as a
      biomarker for the accurate diagnosis and discrimination of PaC-DM from healthy
      controls and non-cancer new-onset T2DM.

PMID- 25991017
TI  - Rotenone affects p53 transcriptional activity and apoptosis via targeting SIRT1
      and H3K9 acetylation in SH-SY5Y cells.
AB  - The protein deacetylase SIRT1 has been recognized to exert its protective effect
      by directly deacetylasing histone and many other transcriptional factors
      including p53. However, the effect of SIRT1 on p53 expression at the
      transcriptional level still remains to be elucidated. In this study, we found
      that rotenone treatment decreased cell viability, induced apoptosis, reduced
      SIRT1 level, and promoted p53 expression. Pre-treatment with resveratrol, a SIRT1
      activator, could attenuate rotenone-induced cell injury and p53 expression,
      whereas down-regulation of SIRT1 directly increased p53 expression. Moreover,
      chromatin immunoprecipitation experiments showed that SIRT1 bound to H3K9 within
      the p53 promoter region, and this binding resulted in decreased H3K9 acetylation
      and increased H3K9 tri-methylation, thereby inhibiting p53 gene transcription. In
      conclusion, our data indicate that rotenone promotes p53 transcription and
      apoptosis through targeting SIRT1 and H3K9. This leads to nigrostriatal
      degeneration, the main pathogenic mechanism of motor features of Parkinson's
      disease. SIRT1, a deacetylase enzyme, has neuroprotective effects for Parkinson's
      disease via targeting various factors. Resveratrol activated SIRT1 can target
      H3K9 and regulate p53 gene expression at the transcriptional level, thus
      inhibiting p53 transcription to enhance neuroprotection, alleviating rotenone
      induced dopaminergic neurodegeneration. We think these findings should provide a
      new strategy for the treatment of Parkinson's disease.

PMID- 25991018
TI  - Cardiac allograft pathology: A clinicopathologic correlation.
AB  - The relationships among cardiac allograft pathology, clinical course, and results
      of endomyocardial biopsies in 55 transplanted adult hearts from 43 autopsies and
      12 retransplants were studied. The mean survival was 8.9 months. All patients
      received cyclosporin-A immunosuppressive therapy. Histologic assessment of left
      and right ventricles (LV and RV) and coronary arteries allowed comparison of the
      following regions of each ventricle: endocardium, subendocardium, myocardium,
      epicardium, epicardial coronary arteries, and intramyocardial arteries.
      Histologic and clinical features were compared using Fisher's exact test.
      Survival curve analysis (Wilcoxon's rank sum test) for each histologic feature
      was performed to define a statistical image of the significant pathologic
      features of allografts with longer survival. Pathologic changes were similar in
      LV and RV. Cellular infiltrate was equivalent transmurally in both ventricles.
      Subendocardial changes in the right ventricle generally reflected the same
      pathologic changes elsewhere in LV and RV. A history of at least two rejection
      episodes correlated with a perimyocytic pattern of LV fibrosis. Infiltrate and
      fibrosis in the epicardium and irregularity of the epicardial-myocardial junction
      and were more frequent in longer-surviving allografts and correlated with
      myocardial and coronary artery pathology. No significant correlation was found
      between subendocardial or myocardial pathological changes and coronary artery
      pathology. The statistical model proved to be a useful approach to the study of
      large numbers of clinicopathologic variables and gave results that were
      pathologically sound. 

PMID- 25991019
TI  - Absence of Trypanosoma cruzi myocardial infection reactivation in Chagas' heart
      transplant.
AB  - The risk of Trypanosoma cruzi myocardial infection reactivation after
      immunosuppressive therapy has led to precluding heart transplantation as a
      therapeutic procedure for patients with end-stage Chagas' heart disease. We
      report a case of an orthotopic heart transplantation in a 43-year-old critically
      ill chagasic patient with an uneventful postoperative period. He was treated with
      azathioprine and cyclosporine to control graft rejection and showed no
      reactivation of the chagasic infection. One year following surgery, the patient
      is doing well. Nonsteroidal therapy appears not to reactivate T. cruzi infection
      in transplant chagasic patients. 

PMID- 25991020
TI  - Hypertrophic cardiomyopathy in pigs: quantitative pathologic features in 55
      cases.
AB  - naturally occurring hypertrophic cardiomyopathy (HCM) was diagnosed in 55
      purebred pigs 6 to 12 months of age. Ten (18%) of the pigs died suddenly during
      auction or shipment or were found dead by their keepers. The other 45 pigs failed
      to meet the criteria for brediing stock. Forty-six purebred and 64 hybrid pigs
      were studied for control. Heart weights were significantly heavier (p < 0.001) in
      the pigs with HCM (473.5 +/- 31.8 g; heart weight [HW]/body weight [BW] ratio 4.6
      +/- 0.7) than in the purebred (334.4 +/- 29.7 g; HW/BW 3.4 +/- 0.3) and hybrid
      (344.3 +/- 28.9 g; HW/BW 3.4 +/- 0.1) pigs without HCM. The ventricular septum
      (VS) in the 55 pigs with HCM was significantly thicker (26.0 +/- 3.1 mm; p <
      0.001) than in the purebred (19.6 +/- 2.6 mm) and hybrid (14.1 +/- 0.5 mm) pigs
      without HCM. The left ventricular free wall (LV) was significantly thicker (p <
      0.001) in the pigs with HCM (20.0 +/- 2.7 mm) than in the purebred (18.1 +/- 2.1
      mm) and hybrid (15.6 +/- 0.3 mm) pigs without HCM. Asymmetric septal hypertrophy
      was evident because the ratio of VS to LV was significantly greater (p < 0.001)
      in the pigs with HCM (1.3 +/- 0.2) than in the purebred (1.0 +/- 0.2) and hybrid
      (0.9 +/- 0.01) pigs without HCM. The anterior portion of the VS appeared to bulge
      into and impinge upon the left ventricular outflow tract, in which a fibrotic
      endocardial plaque was often seen. Histologic features included marked muscle
      cell disorganization in the VS, LV, right ventricular free wall. Abnormal
      intramural coronary arteries and myocardial fibrosis were seen in most pigs with
      HCM. Silver impregnation stains showed that there were marked increases in
      perimysial coils, pericellular weaves, and cell-to-cell struts. Matrix
      disorientation was evident in the hearts with HCM. Quantitation revealed that the
      collagen protein in the hearts with HCM (23.8 +/- 2.8 MUg/mg protein) was
      significantly higher (p < 0.001) than in the hearts of purebred (15.7 +/- 1.8
      MUg/mg protein) and hybrid (13.9 +/- 4.2 MUg/m pprotein) pigs without HCM. Total
      muscle protein in the hearts of the purebred pigs with (51.6 +/- 3.3 mg) and
      without (51.9 +/- 3.0 mg) HCM was not different; however, in hearts with HCM
      (51.6 +/- 3.3 mg) it was significantly higher (p < 0.001) than in those of hybrid
      pigs (47.6 +/- 4.4 mg) without HCM. There was 47% to 52% more stainable collagen
      in the heart with HCM (44.7 +/- 5.2 MUg collagen/mg protein) than in the purebred
      (30.3 +/- 4.0 MUg collagen/mg protein) and hybrid (28.3 +/- 8.1 MUg collagen/mg
      protein) hearts without HCM. Gross and histologic features and connective tissue
      abnormalities in the pigs with HCM were strikingly similar to those in humans,
      cats, and dogs with HCM. Thus we conclude that spontaneous porcine HCM presents a
      new and important model for the cardiovascular investigator. 

PMID- 25991021
TI  - Anomalous origin of the left circumflex coronary artery from the right aortic
      sinus of valsalva and sudden death.
AB  - Anomalous origin of the left circumflex coronary artery from the right aortic
      sinus is generally considered a benign condition. We report a 53-year-old man
      with clinical and pathologic evidence of myocardial infarction and sudden death
      in the setting of this anomaly, with no evidence of obstructive coronary
      atherosclerosis. 

PMID- 25991022
TI  - Dissection and intussusception of the common carotid artery following
      endarterectomy.
AB  - We describe a 67-year-old man who developed a dissection of the right common
      carotid arterial wall with intussusception two years following endarterectomy for
      atherosclerosis. We suggest that the previous surgical procedure resulted in a
      thinned and weakened media. With a disruption of the intima, a dissection into
      the inner third of the media formed, and blood in the false lumen buckled the
      intima into the lumen of the blood vessel. Hemodynamic forces then probably
      played a role in the propagation of the dissection and the formation of an
      intussusception. Complete occlusion by thrombus followed, resulting in a massive
      cerebral infarct, the likely terminal event. Carotid endarterectomy rarely may be
      followed by dissection of the vascular wall and intussusception. 

PMID- 25991023
TI  - Myocardial ANP expression in Pompe's disease: An immunohistochemical study.
AB  - The expression of atrial natriuretic peptide (ANP) was analyzed in the atrial and
      ventricular myocardium in three cases of Pompe's disease (glycogen storage
      disease of the myocardium), using an immunoperoxidase technique. The cytoplasm of
      almost all atrial myocytes and some subendocardial myocytes from the right and
      left ventricles were ANP-positive, excluding the typical central vacuole, which
      was occupied by glycogen. Ventricular ANP expression was usually more prominent
      in left ventricular samples, and its distribution was similar to that described
      in dilated, hypertrophic, restrictive, or ischemic heart disease; however, the
      enlargement of the myocytes in Pompe's disease is not caused by hypertrophy. We
      conclude that the atrial myocytes in Pompe's disease maintain ANP expression,
      despite severe cytoplasmic vacuolization. These results suggest that ventricular
      ANP expression may be related to mechanical stimuli, such as the increase in wall
      stress, and not directly related to myocyte hypertrophy. 

PMID- 25991024
TI  - Cardiac pseudoaneurysm caused by mitral ring calcification.
AB  - A case of left ventricular pseudoaneurysm caused by mitral ring calcification
      (MRC) in a 71-year-old woman is reported. MRC was initially detected by two
      dimensional echocardiography. Two months later, rupture of the posterior wall and
      pseudoaneurysm formation were diagnosed. Mitral value replacement and
      reconstructive surgery of the myocardial wall were performed. The patient died 46
      days after the operation. At autopsy, there was no histopathological evidence of
      myocardial infarction, infective endocarditis, or other conditions affecting the
      cardiac endomyocardium. Pseudoaneurysm apparently resulted from left atrial and
      ventricular tears caused by MRC. 

PMID- 25991025
TI  - Embryological evidence for the formation of a quadricuspid aortic valve in the
      Syrian hamster.
AB  - Congenital quadricuspid aortic valve is a rare anomaly, the morphogenesis of
      which remains unclear. In this study we report the case of a Syrian hamster
      embryo that presented an aortic valve with four valve cushions instead of three.
      The embryo, aged 12 days and 2 hours postcoitum, was at an early stage of
      valvulogenesis. It was examined using semithin sections of the heart. Two of the
      four valve cushions were located, one in the dorsal and the other in the left
      ventral position, corresponding, respectively, to the dorsal and left valve
      cushions of a normal aortic valve. The remaining two cushions were situated in
      the right-ventral position. They were joined at the level of their basal portions
      and were less developed in size than the other cushions. This report seems to be
      the first embryological evidence for the formation of a quadricuspid aortic
      valve. The present findings strongly suggest that the anomalous valve originated
      from three mesenchymal anlagen and that the supernumerary valve cushion resulted
      from the division of the anlagen that normally gives rise to the right valve
      cushion. 

PMID- 25991027
TI  - Measurements of jugular, portal, femoral, and calf vein cross-sectional area for
      the assessment of venous blood redistribution with long duration spaceflight
      (Vessel Imaging Experiment).
AB  - PURPOSE: To determine if 6 months in microgravity resulted in significant changes
      in the major central and peripheral veins indicating a redistribution of venous
      blood flow. METHODS: Ten astronauts participated in the study. Jugular vein (JV),
      portal vein (PV), femoral vein (FV), tibial vein (TibV), and gastrocnemius vein
      (Gast V) were assessed by echography for the measurement of vessel cross
      sectional area. Inflight exams were conducted by astronauts using a volume
      capture method in which images collected were processed to produce a 3D
      reconstruction of the vessel which was later analyzed by a trained sonographer.
      Measurements were conducted pre-flight, at the beginning of the flight (day 15),
      near the end of the flight (4-5.5 months), and post-flight. RESULTS: During the
      flight, JV, PV, JV/PV ratio, and FV were found significantly increased from pre
      flight at 15 days and 4-5.5 months (JV: 178 and 225%, p < 0.05; PV: 36 and 45%, p
      < 0.05; JV/PV ratio: 102 and 120%, p < 0.05; FV: 124 and 169%, p < 0.05).
      Conversely, calf veins decreased at day 15 and at 4-5.5 months (TibV: -45 and-52
      %, p < 0.05; Gast V: -68 and -55%, p < 0.05). All veins returned to base line
      conditions 4 days after returning to Earth. CONCLUSIONS: The increase in JV, PV,
      and FV cross-sectional area during spaceflight confirmed that there was venous
      blood pooling in the cephalic, splanchnic, and pelvic regions. Further
      investigation is needed to determine the consequences of this fluid stagnation on
      the brain, eye, splanchnic, and pelvic organ morphology and or function.

PMID- 25991028
TI  - Evidence informed decision making: the use of "colloquial evidence" at nice.
AB  - OBJECTIVES: Colloquial evidence (CE) has been described as the informal evidence
      that helps provide context to other forms of evidence in guidance development.
      Despite challenges around quality, and the potential biases, the use of CE is
      becoming increasingly important in assessments where scientific literature is
      sparse and to also capture the experience of all stakeholders in discussions,
      including that of experts and patients. We aimed to ascertain how CE was being
      used at the National Institute for Health and Care Excellence (NICE). METHODS:
      Relevant data corresponding to the use of CE was extracted from all NICE
      technical and process manuals by two reviewers and quality assured and analyzed
      by a third reviewer. This was considered in light of the results of a focused
      literature review and a combined checklist for quality assessment was developed.
      RESULTS: At NICE, CE is utilised across all guidance producing programmes and at
      all stages of development. CE could range from information from experts and
      patient/carers, grey literature (including evidence from websites and policy
      reports) and testimony from stakeholders through consultation. Six tools for
      critical appraisal of CE were available from the literature and a combined best
      practice checklist has been proposed. CONCLUSIONS: As decisions often need to be
      made in areas where there is a lack of published scientific evidence, CE is
      employed. Therefore to ensure its appropriateness the development of a validated
      CE data quality check-list to assist decision makers is essential and further
      research in this area is a priority.

PMID- 25991030
TI  - Composition of bacterial and archaeal communities during landfill refuse
      decomposition processes.
AB  - Little is known about the archaeal and the bacterial diversities in a landfill
      during different phases of decomposition. In this study, the archaeal and the
      bacterial diversities of Laogang landfill (Shanghai, China) at two different
      decomposition phases (i.e., initial methanogenic phase (IMP) and stable
      methanogenic phase (SMP)), were culture-independently examined using PCR-based
      454 pyrosequencing. A total of 47,753 sequences of 16S rRNA genes were retrieved
      from 69,954 reads and analyzed to evaluate the diversities of the archaeal and
      bacterial communities. The most predominant types of archaea were
      hydrogenotrophic Methanomicrobiales, and of bacteria were Proteobacteria,
      Firmicutes, and Bacteroidetes. As might be expected, their abundances varied at
      decomposition phases. Archaea Methanomicrobiales accounts for 97.6% of total
      archaeal population abundance in IMP and about 57.6% in SMP. The abundance of
      archaeal genus Halobacteriale was 0.1% in IMP and was 20.3% in the SMP. The
      abundance of Firmicutes was 21.3% in IMP and was 4.3% in SMP. The abundance of
      Bacteroidetes represented 11.5% of total bacterial in IMP and was dominant
      (49.4%) in SMP. Both the IMP and SMP had unique cellulolytic bacteria
      compositions. IMP consisted of members of Bacillus, Fibrobacter, and Eubacterium,
      while SMP harbored groups of Microbacterium. Both phases had Clostridium with
      different abundance, 4-5 folds higher in SMP. 

PMID- 25991029
TI  - Patterns of left ventricular remodeling in aortic stenosis: therapeutic
      implications.
AB  - OPINION STATEMENT: Aortic valve stenosis is characterized by indolent progression
      followed by the late development of symptoms once left ventricular compensatory
      mechanisms fail. In this review, we describe the left ventricular response to
      aortic stenosis. Specifically, we highlight the process of adaptive remodeling,
      which begins as a beneficial compensatory mechanism but ultimately transitions to
      a maladaptive process characterized by inappropriate left ventricular
      hypertrophy, interstitial fibrosis, and diminished contractility. Myocardial
      fibrosis ensues as the remodeling process progresses with potentially
      irreversible consequences on diastolic and systolic function and on clinical
      symptoms and outcomes. Recent data suggest that fibrosis is largely responsible
      for the development of symptoms in patients with severe aortic stenosis, which
      unfortunately implies that fibrosis may be advanced by the time clinical
      symptomatology triggers evaluation for aortic valve replacement. Interstitial
      fibrosis persists for years after valve replacement and, when severe, can lessen
      the clinical benefits of valve replacement. Further evaluation of noninvasive
      measures capable of assessing the extent of maladaptive left ventricular
      remodeling and of predicting its reversal are desperately needed in order to
      enhance the personalized delivery of aortic valve replacement for severe aortic
      stenosis. We support aggressive assessment of symptomatic status with more
      frequent clinical follow-up and exercise testing in asymptomatic individuals with
      severe left ventricular hypertrophy or impaired longitudinal contractility.
      However, whether early valve replacement is advantageous in patients with
      evidence of maladaptive left ventricular remodeling in the absence of symptoms
      remains unknown, but is certainly worthy of further investigation.

PMID- 25991031
TI  - First Implantation of Repositionable Lotus Valve in a Degenerated Trifecta
      Bioprosthesis.

PMID- 25991032
TI  - Evaluation of scar penetrating neovascularisation in a rat epigastric flap model.
AB  - AIM: The aim of this study is to investigate neovascularisation patterns in the
      presence of scar tissue and to compare the venous vs arterial components of the
      scar penetrating neovascularisation. METHODS: Forty male Spraque-Dawley Rats,
      which were divided into four groups, were used for this study. At the beginning
      of the study a vertical midline abdominal incision was made to all animals. Six
      weeks after the incisions were made, epigastric flaps based on inferior
      epigastric vessels were raised. In the first group both left and right epigastric
      artery and veins were protected. In the second group only the right epigastric
      artery and vein was protected. In the third group, besides the right epigastric
      artery and vein, only the left epigastric artery was kept intact. In the fourth
      group, besides the right epigastric artery and vein, only the left epigastric
      vein was kept intact. RESULTS: The percentages of necrotic areas on the flaps
      were statistically evaluated. The percentages of the necrotic areas on the left
      side of the flaps were significantly higher in the second group (p = 0.0305).
      Total flap area necrosis was also significantly higher in the second group (p =
      0.026). In each group, vessel formations were identified which were extending
      through the midline scar tissue in the angiographic evaluations. CONCLUSIONS:
      These results suggest that scar penetrating neovascularisation on an epigastric
      flap with one sided pedicle, which is supported by a vein or an artery on the
      contralateral side, can be enough to facilitate the flap circulation.

PMID- 25991033
TI  - A "blanking effect" for surface features: Transsaccadic spatial-frequency
      discrimination is improved by postsaccadic blanking.
AB  - Although saccadic eye movements occur frequently-about three or four times a
      second-humans are astonishingly blind to transsaccadic changes. Locational
      displacements of the saccade target of up to 2 deg of visual angle, and even
      large changes of a visual scene, can go unnoticed. For a long time, this
      insensitivity was ascribed to deficits in transsaccadic memory: Only a coarse,
      (spatially) imprecise representation would be retained across a saccade. This
      assumption was contradicted by Deubel's and Schneider's (Behavioral and Brain
      Sciences 17:259-260, 1994) striking finding that locational discrimination
      performance across a saccade is greatly improved by inserting a short
      postsaccadic blank. Surprisingly, the question of whether blanking effects occur
      also for other forms of transsaccadic changes (i.e., surface-feature changes) has
      been widely ignored. We tested this question by means of a transsaccadic change
      in spatial frequency. Postsaccadic blanking facilitated spatial-frequency
      discrimination, but to a smaller amount than the usual blanking effects obtained
      with locational displacements. This finding bears important implications for
      models of visual stability and transsaccadic memory.

PMID- 25991034
TI  - Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of
      natural killer cell function and cytotoxicity.
AB  - NK cells play a key role in innate elimination of virally infected or neoplastic
      cells but they can be circumvented by immunoevasive mechanisms enabling viral
      spread or tumor progression. Engagement of the NKG2D activating receptor with
      soluble forms of its ligand is one such mechanism of inducing NK cell
      hyporesponsiveness. Interestingly, this immunoevasive strategy among others is
      described at the maternal-fetal interface where tolerance of the semi-allogeneic
      fetus is required to allow successful human pregnancy. Understanding of maternal
      fetal tolerance is increasing but mechanisms preventing alloreactivity of fetal
      immune cells against the maternal host are less well understood. The study of
      umbilical cord blood has enabled insight of the fetal immune system, which
      appears immature and inert. We have found that soluble NKG2D ligands (sNKG2DLs)
      are present in cord blood plasma (CBP) and associate with adult NK cell
      hyporesponsiveness demonstrated by reduced CD107a expression and secretion of IFN
      gamma upon stimulation. The capacity of NK cells to kill K562 cells or
      proliferate was also reduced by incubation with CBP; however, physical removal of
      sNKG2DL from CBP restored K562 lytic function and NKG2D expression. Therefore,
      our results strongly suggest sNKG2DLs are expressed in CBP as a mechanism of
      fetal-maternal tolerance in human pregnancy. 

PMID- 25991035
TI  - Dual functions of GmTOE4a in the regulation of photoperiod-mediated flowering and
      plant morphology in soybean.
AB  - Flowering time, maturity, and plant morphology have considerable effects on the
      adaptation and grain yield of soybean (Glycine max). The identification of novel
      genes and an understanding of their molecular basis are critical to improve
      soybean productivity. In this study, we cloned a flowering time related APETALA2
      like gene GmTOE4a and generated GmTOE4a-overexpressing lines in the cultivar
      Williams 82. The transgenic lines exhibited late flowering both under long day
      and short day conditions, and repressed the flowering-related genes, including
      GmFT2a, GmFT5a, GmAP1, and GmLFY, whereas the flowering repressors GmFT4 and
      miR156 were upregulated. Interestingly, GmTOE4a was also mediated by photoperiod
      via maturity genes E3 and E4, which encode photoreceptors in soybean. Further,
      miR172-mediated GmTOE4a, which regulates flowering in soybean, is different in
      Arabidopsis in that it is dependent on the CONSTANS-like gene GmCOL1a. In
      addition to its effect on flowering time, GmTOE4a regulated plant morphology,
      increased stem thickness, and reduced plant height, internode length and leaf
      size, which are important agronomic traits that enhance the capacity to resist
      lodging and increase soybean yield. This is useful information to understand the
      molecular mechanism of flowering time and plant morphology in soybean and will
      greatly influence soybean yield improvement. 

PMID- 25991036
TI  - Functional architecture of two exclusively late stage pollen-specific promoters
      in rice (Oryza sativa L.).
AB  - Late stage pollen-specific promoters are important tools in crop molecular
      breeding. Several such promoters, and their functional motifs, have been well
      characterized in dicotyledonous plants such as tomato and tobacco. However,
      knowledge about the functional architecture of such promoters is limited in the
      monocotyledonous plant rice. Here, pollen-late-stage-promoter 1 (PLP1) and pollen
      late-stage-promoter 2 (PLP2) were characterized using a stable transformation
      system in rice. Histochemical staining showed that the two promoters exclusively
      drive GUS expression in late-stage pollen grains in rice. 5' deletion analysis
      revealed that four regions, including the -1159 to -720 and the -352 to -156
      regions of PLP1 and the -740 to -557 and the -557 to -339 regions of PLP2, are
      important in maintaining the activity and specificity of these promoters. Motif
      mutation analysis indicated that 'AGAAA' and 'CAAT' motifs in the -740 to -557
      region of PLP2 act as enhancers in the promoter. Gain of function experiments
      indicated that the novel TA-rich motif 'TACATAA' and 'TATTCAT' in the core region
      of the PLP1 and PLP2 promoters is necessary, but not sufficient, for pollen
      specific expression in rice. Our results provide evidence that the enhancer motif
      'AGAAA' is conserved in the pollen-specific promoters of both monocots and
      eudicots, but that some functional architecture characteristics are different. 

PMID- 25991037
TI  - Cost-utility analysis of nanoparticle albumin-bound paclitaxel (nab-paclitaxel)
      in combination with gemcitabine in metastatic pancreatic cancer in Spain: results
      of the PANCOSTABRAX study.
AB  - The PANCOSTABRAX study evaluated the cost-effectiveness of nanoparticle albumin
      bound paclitaxel (nab-paclitaxel) in combination with gemcitabine (GEM) versus
      GEM alone in the treatment of patients with metastatic pancreatic cancer in
      Spain. Efficacy data were obtained from the MPACT study and were modeled to a
      lifetime horizon using a Markov model. The analysis was performed from the
      payer's perspective. Use of resources and key assumptions of the analysis were
      validated by a panel of oncologists. The addition of nab-paclitaxel to GEM showed
      higher effectiveness results (0.156 additional quality adjusted life years) at a
      higher cost (?6,477), resulting in a cost per quality-adjusted life years gained
      of ?41,519. The combination of nab-paclitaxel and GEM has been shown to be an
      effective and well-tolerated option for the treatment of metastatic pancreatic
      cancer and, in addition to becoming the new standard of care, could also be
      considered a cost-effective option. 

PMID- 25991038
TI  - The severity of steatosis influences liver stiffness measurement in patients with
      nonalcoholic fatty liver disease.
AB  - In nonalcoholic fatty liver disease, the influence of severity of steatosis on
      liver stiffness measurement (LSM) is poorly studied and still debated. We
      assessed the impact of steatosis severity and its ultrasonographic (US) sign,
      severe bright liver echo pattern, on LSM values and on transient elastography
      accuracy for the diagnosis of liver fibrosis in a cohort of consecutive patients
      with nonalcoholic fatty liver disease. Patients (n = 253) were assessed by
      clinical, US, and histological (Kleiner score) features. Transient elastography
      was performed using the M probe. Among patients with low amounts of fibrosis (F0
      F1 and F0-F2), median LSM values, expressed in kilopascals, were significantly
      higher in subjects with severe steatosis (>=66% at liver biopsy) compared to
      those without (F0-F1 6.9 versus 5.8, P = 0.04; F0-F2 7.4 versus 6.0, P = 0.001)
      as well as in patients with severe bright liver echo pattern on US compared to
      their counterparts (F0-F1 7.3 versus 5.6, P = 0.001; F0-F2 7.6 versus 6.0, P <
      0.001). In subjects without significant fibrosis (F0-F1) and without severe
      fibrosis (F0-F2), a higher rate of false-positive LSM results was observed in
      patients with steatosis >=66% compared to those without (F0-F1 23.6% versus
      14.9%, F0-F2 33.3% versus 13.2%) and in patients with severe bright liver echo
      pattern on US (F0-F1 22.2% versus 15.4%, F0-F2 28.8% versus 15.6%) compared to
      their counterparts. CONCLUSIONS: In patients with nonalcoholic fatty liver
      disease, the presence of severe steatosis, detected by histology or by US, should
      always be taken into account in order to avoid overestimations of liver fibrosis
      assessed by transient elastography.

PMID- 25991039
TI  - In silico discovery of a nearly complete mitochondrial genome Numt in the dog
      (Canis lupus familiaris) nuclear genome.
AB  - Through bacterial cloning, a non-specific product co-amplified in a previous
      whole mitochondrial genome study of Canis lupus familiaris was identified as part
      of a Numt on chromosome 29 of the dog. Even though further analysis confirmed the
      fidelity of the mitochondrial genome sequencing results, it still highlighted the
      risk of Numt contamination. A computer-based search of the dog's nuclear genome
      for segments homologous to the mtDNA sequence revealed the extent of this risk.
      Over 150 Numts of various sizes were observed throughout all but two chromosomes,
      covering all positions of the mtDNA. One of the Numts on chromosome 11 even
      covered over 95 % of the entire dog mtDNA sequence. This comprehensive list of
      Numts was provided to assist researchers with the evaluation of dog mtDNA
      sequencing protocols for Numt co-amplification. 

PMID- 25991040
TI  - Critical Reflection: A Transformative Learning Process Integrating Theory and
      Evidence-Based Practice.

PMID- 25991042
TI  - C4d Staining in the Diagnosis of C3 Glomerulopathy.

PMID- 25991041
TI  - C4d as a Diagnostic Tool in Proliferative GN.
AB  - Proliferative GN is classified as immune complex-mediated or complement-mediated
      (C3 glomerulopathy). Immune complex-mediated GN results from glomerular
      deposition of immune-complexes/Ig and C3; the C3 is derived from activation of
      the classical and/or lectin pathways of complement. C3 glomerulopathy results
      from deposition of C3 and other complement fragments with minimal or no
      deposition of immune complexes/Ig; the C3 is derived from activation of the
      alternative pathway of complement. C4d is a byproduct of activation of the
      classic and lectin pathways. Although widely used as a marker for antibody
      mediated rejection, the significance of C4d in C3 glomerulopathy is undetermined.
      We studied glomerular C4d staining in 18 biopsy specimens of immune-complex GN,
      30 biopsy specimens of C3 GN, and 13 biopsy specimens of postinfectious GN. All
      specimens of immune complex-mediated GN, except two specimens of IgA nephropathy
      and one specimen of sclerosing membranoproliferative GN, showed bright (2-3+) C4d
      staining. The staining pattern of C4d mirrored the staining patterns of Ig and
      C3. Conversely, C4d staining was completely negative in 24 (80%) of 30 specimens
      of C3 glomerulopathy, and only trace/1+ C4d staining was detected in six (20%)
      specimens. With regard to postinfectious GN, C4d staining was negative in six
      (46%) of 13 specimens, suggesting an abnormality in the alternative pathway, and
      it was positive in seven (54%) specimens. To summarize, C4d serves as a positive
      marker for immune complex-mediated GN but is absent or minimally detected in C3
      glomerulopathy. 

PMID- 25991043
TI  - Differential levels of cathepsin B and L in serum between young and aged healthy
      people and their association with matrix metalloproteinase 2.
AB  - OBJECTIVE: Most publications describe cathepsin B and L as tumor and metastasis
      factors. These proteases also play a very important role in aging process. The
      aim of this study was to evaluate the serum level of cathepsin B and L with aging
      and their association with matrix metalloproteinase 2 (MMP2), which was reported
      to associate with age-related diseases. METHODS: This research was conducted
      using blood samples provided by healthy people (n=90, 63 men and 27 women).
      Subjects were subdivided into groups with respect to age: young (about 18-30
      years old, n=30), middle age (about 36-50 years old, n=30), and aged (above 56
      years old, n=30). Altered serum level of cathepsin B, cathepsin L, and MMP2 with
      aging was studied by enzyme-linked immunosorbent assay (ELISA) and Western
      blotting using discriminative antibodies specific for each factor. RESULTS: ELISA
      and Western blotting revealed that the serum level of cathepsin L and MMP2, but
      not cathepsin B significantly decreased in aged group compared with young group.
      Cathepsin L positively correlates with MMP2 among the whole healthy people
      (r(2)=0.869, p<0.0001). CONCLUSION: The serum level of cathepsin L decreased with
      age, while cathepsin B remained no significant difference between young and aged
      individuals. In addition, cathepsin L positively correlates with MMP2. PRACTICE:
      The cathepsin L may be used as a monitoring index in age-related diseases.
      IMPLICATIONS: In addition to cathepsin B, cathepsin L may be also involved in the
      aging process.

PMID- 25991044
TI  - Clinical value of NT-proBNP assay in the emergency department for the diagnosis
      of heart failure (HF) in very elderly people.
AB  - OBJECTIVE: Scanty data are available on the accuracy of NT-proBNP in the
      diagnosis of HF and effects of comorbidities in very elderly patients. METHODS:
      Symptoms, signs, NT-proBNP, eGFR, Ht, CRP and the presence of cardiomegaly and
      pleuric effusion were assessed in 895 consecutive patients aged 86+/-4.3 years
      admitted to Emergency Department and used to define the diagnosis of HF according
      to Framingham criteria. Receiver operating characteristic curves (ROC) were used
      to calculate diagnostic performance and cutoff of NT-proBNP. Sensitivity (Sn),
      specificity (Sp), positive predictive value (PPV) and negative predictive value
      (NPV) were computed for all NT-proBNP cutoffs. RESULTS: Satisfactory diagnostic
      performance was obtained with a lower threshold of 980pg/mL (Sn 0.95; NPV 0.90)
      and a higher threshold of 5340 (Sp 0.85; PPV 0.76) but with 42.4% of patients in
      the uncertainty area. We determined a second couple of cutoffs (1470-4200) that
      reduced the gray-area to 27.4%, maintaining an acceptable diagnostic performance
      compared to commonly used cutoffs (300-1800). Ht, CRP and eGFR all correlated
      with NT-proBNP in groups with and without HF but none affected diagnostic
      performance. CONCLUSION: NT-proBNP performs satisfactorily for the diagnosis of
      HF in very elderly patients. Proposed threshold couple, compared with the most
      used cutoffs, showed a gain in Sp and PPV with a slightly lower performance in Sn
      and NPV and with a decrease in the gray-area with the second one. Our data do not
      support the use of different NT-proBNP cutoffs depending on eGFR, Ht and CRP.

PMID- 25991045
TI  - Is the fracto-mechanoluminescence of ZnS:Mn phosphor dominated by charged
      dislocation mechanism or piezoelectrification mechanism?
AB  - Mathematical approaches made for both the charged dislocation model and
      piezoelectrically induced electron bombardment model of fracto
      mechanoluminescence (FML), the luminescence induced by fracture of solids, in
      ZnS:Mn phosphor indicate that the piezoelectrically induced electron bombardment
      model provides a dominating process for the FML of ZnS phosphors. The
      concentration of 3000 ppm Mn(2+) is optimal for ML intensity of ZnS:Mn phosphor.
      The decay time of ML gives the relaxation time of the piston used to deform the
      sample and the time tm of maximum of ML is controlled by both the relaxation time
      of the piston and decay time of charges on the newly created surfaces of
      crystals. As the product of the velocity of dislocations and pinning time of
      dislocations gives the mean free path of a moving dislocation. Both factors play
      an important role in the ML excitation of impurity doped II-VI semiconductors.
      The linear increase of total ML intensity IT with the impact velocity indicates
      that the damage increases linearly with impact velocity of the load. Thus, the ML
      measurement can be used remotely to monitor the real-time damage in the
      structures, and therefore, the ML of ZnS:Mn phosphor has also the potential for a
      structural health monitoring system.

PMID- 25991046
TI  - Social dominance theory and medical specialty choice.
AB  - Understanding how medical students select their specialty is a fundamental issue
      for public health and educational policy makers. One of the factors that students
      take into account is a specialty's prestige which hinges partly on its focus on
      technique rather than whole person. We examine the potential of a psychological
      framework, social dominance theory, to explain why some students, and not others,
      are drawn to more prestigious, technique-oriented specialties, based on their
      desire for hierarchy. We conducted a cross-sectional study among medical students
      at Institution X (N = 359). We examined the link between medical students'
      characteristics i.e. social dominance orientation (SDO), gender, age, and their
      career intention. We also examined level of medical students' SDO at different
      stages of the curriculum. SDO scores were significantly associated with technique
      oriented career intentions (OR 1.56; 95 % CI [1.18, 2.06]; p = 0.001). The effect
      was independent of gender. Medical students' SDO scores were significantly higher
      in later stages of the medical curriculum (F = 6.79; p = 0. 001). SDO is a
      significant predictor of medical students' career intention. SDO scores are
      higher in students during the clinical phase of the curriculum. Medical
      socialization, involving the internalization of implicit and explicit norms,
      particularly in hospital settings, is likely to underpin our findings. This
      theory illuminates consistent findings in the literature on specialty prestige
      and the influence of medical school on career choice. 

PMID- 25991047
TI  - Acute care surgery in Rwanda: Operative epidemiology and geographic variations in
      access to care.
AB  - BACKGROUND: Surgical management of emergent, life-threatening diseases is an
      important public health priority. The objectives of this study were to (1)
      describe acute care general surgery procedures performed at the largest referral
      hospital in Rwanda and (2) understand the geographic distribution of disease
      presentations and referral patterns. METHODS: We performed a retrospective review
      of prospectively collected acute care surgery cases performed at the Centre
      Hospitalier Universitaire de Kigali (CHUK) in Rwanda between June 1 and December
      1, 2011. Using Pearson's chi(2) test and the Fisher exact test, we compared cases
      originating from within Kigali and transfers from other provinces. Geospatial
      analyses also were used to further describe transfer patterns. RESULTS: During
      the study period, 2,758 surgical interventions were performed, of which 25.6%
      (707/2,758) were general surgery operations. Of these, 45.4% (321/707) met the
      definition of acute care surgery. Only about one-third-32.3% (92/285)-of patients
      resided within Kigali, whereas about two-thirds-67.7% (193/285)-were transferred
      from other provinces. Most patients transferred from other provinces were younger
      than 18 years of age (40.4%; 78/193), and 83.0% (39/47) of patients older than 50
      years of age originated from outside of Kigali. Specific operative indications
      and surgical procedures varied substantially between patients from Kigali and
      patients transferred from other provinces. CONCLUSION: Emergency surgical
      conditions remain important contributors to the global burden of disease,
      particularly in low- and middle-income countries. Geographic variations exist in
      terms of operative diagnoses and procedures, which implies a need for improved
      access to surgical care at the district level with defined transfer mechanisms to
      greater-level care facilities when needed.

PMID- 25991049
TI  - Long-term viral shedding and viral genome mutation in norovirus infection.
AB  - The duration of viral shedding in the patients from two outbreaks and four
      sporadic cases of norovirus (NoV) infections was investigated. The longest period
      of viral shedding into feces was for 173 days in an inpatient from one case of
      outbreak. The VP1 sequence from two long-term viral shedding cases in the
      outbreak revealed four synonymous and one non-synonymous mutations in one
      inpatient at 26 days from the onset of illness, and nine synonymous and two non
      synonymous mutations and a deletion, 10 synonymous mutations and a deletion in
      other inpatient at 29 days and 54 days from the onset of illness, respectively.
      Ten of the 11 amino acid positions detected in these two inpatients were in the
      outermost P2 domain of the viral capsid protein, and mutations at positions 295,
      297, and 394 were shared in the inpatients. Mutations in the P2 domain were in
      epitopes A and D or near epitopes A, C, and E, suggesting that the long-term
      carrier state of norovirus infection contributes to the generation of escape
      mutants by host immunoselection.

PMID- 25991048
TI  - Calpain inhibition decreases myocardial apoptosis in a swine model of chronic
      myocardial ischemia.
AB  - INTRODUCTION: Calpain is a family of cysteine proteases that has an important
      role in the initiation, regulation, and execution of cell death. Our recent
      studies using a hypercholesterolemic swine model demonstrated that in the setting
      of the metabolic syndrome, calpain inhibition (CI) improved collateral-dependent
      perfusion and increased expression of proteins implicated in angiogenesis and
      vasodilation. In this study, we hypothesized that CI (by MLD28170) would decrease
      myocardial apoptosis in the same model. METHODS: Yorkshire swine, all fed a high
      cholesterol diet for 4 weeks underwent placement of an ameroid constrictor on the
      left circumflex coronary artery. Three weeks later, animals received either no
      drug, termed the high-cholesterol control group (HCC; n = 8); low-dose CI (0.12
      mg/kg; LCI, n = 9); or high-dose CI (0.25 mg/kg; HCI, n = 8). The high
      cholesterol diet and the CI were continued for 5 weeks, after which the pig was
      humanely killed and the left ventricular myocardium was harvested and analyzed
      via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      staining, oxyblot analysis, and Western blots. Data were analyzed using the
      Kruskal-Wallis test. RESULTS: The percentage of apoptotic cells to total cells in
      ischemic myocardial territory was decreased in the LCI and HCI groups compared
      with the HCC group as shown by TUNEL staining (P = .018). There was a decrease in
      proapoptotic proteins, including cleaved caspase 3, caspase 9, cleaved caspase 9,
      Bax, BAD, p-BAD, and Erk 1/2 (P <= .049 each), but no decrease in caspase 3 (P =
      .737). There was also an increase in antiapoptotic proteins, including BCL-2 and
      p-BCL2 (P <= .025 each). In the ischemic myocardium, several proangiogenic
      proteins were increased in the LCI and HCI groups compared with the HCC group,
      including p-AKT, p-eNOS, and eNOS (P <= .006 each) but there was no increase in
      AKT (P = .311). CI decreased tissue oxidative stress in both the LCI and HCI
      groups compared to the HCC group as shown by oxyblot analysis (P = .021).
      CONCLUSION: In the setting of hypercholesterolemia, CI decreases apoptosis and
      the expression of proteins in proapoptotic signaling pathways. CI also increased
      expression of proteins implicated in anti apoptotic pathways and improves
      oxidative stress in ischemic myocardial tissue.

PMID- 25991050
TI  - Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue
      that can be limited by a COX-2-specific inhibitor.
AB  - In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the
      elicited inflammatory response is considered a key pain mechanism. However,
      inflammatory cytokines are reported in extruded herniated tissue, even before
      monocyte infiltration, suggesting that the tissue itself initiates the
      inflammation. Since herniated tissue swells, we investigated whether this simple
      mechanobiological stimulus alone could provoke an inflammatory response that
      could cause pain. Furthermore, we investigated whether sustained-release
      cyclooxygenase-2 (COX2) inhibitor would be beneficial in such conditions. Healthy
      bovine NP explants were allowed to swell freely or confined. The swelling
      explants were treated with Celecoxib, applied either as a bolus or in sustained
      release. Swelling explants produced elevated levels of interleukin-6 (IL-6) and
      prostaglandin E2 (PGE2 ) for 28 days, while confined explants did not. Both a
      high concentration bolus and 10 times lower concentration in sustained release
      completely inhibited PGE2 production, but did not affect IL-6 production.
      Swelling of NP tissue, without the inflammatory system response, can trigger
      cytokine production and Celecoxib, even in bolus form, may be useful for pain
      control in extruded disc herniation.

PMID- 25991051
TI  - Genetic variability in GLP-1 receptor is associated with inter-individual
      differences in weight lowering potential of liraglutide in obese women with PCOS:
      a pilot study.
AB  - PURPOSE: The weight lowering potential of glucagon-like peptide 1 (GLP-1)
      receptor agonists (RAs) is inter-individually different and clinically
      unpredictable. The potential role of genetic variability of GLP-1R on body weight
      response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has
      not yet been evaluated. METHODS: Fifty-seven obese women with PCOS (aged 30.7 +/-
      7.0, BMI 38.6 +/- 5.3 kg/m(2)) were assigned to liraglutide 1.2 mg QD s.c. for 12
      weeks and classified as strong responders regarding weight loss if they lost 5%
      or more of their initial body weight. They were genotyped for common GLP-1R
      single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of
      measures of obesity were measured before and at the end of the treatment.
      RESULTS: Twenty out of 57 subjects were strong responders and lost 7.38 +/- 1.74
      compared to 2.11 +/- 2.17 kg lost in poor responders. Carriers of at least one
      polymorphic rs10305420 allele had poor treatment response compared to carriers of
      two wild type alleles (OR = 0.27, 95% CI = 0.09-0.85, P = 0.025). Carriers of at
      least one polymorphic rs6923761 allele tended to have stronger treatment response
      compared to carriers of two wild type alleles (OR = 3.06, 95% CI = 0.96-9.74, P =
      0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT)
      comparably decreased in both groups when compared to baseline, whereas no within
      treatment differences were found in androgen profile. Gastrointestinal adverse
      events were transit and balanced between strong and poor responders. CONCLUSIONS:
      GLP-1R rs10305420 polymorphism explained some of the inter-individual differences
      in response to liraglutide regarding weight loss in obese PCOS women.

PMID- 25991053
TI  - Frontotemporal Dementia-Like Syndrome Following Recall of Childhood Sexual Abuse.
AB  - Numerous psychopathological syndromes have been attributed to posttraumatic
      stress, both at the time of the trauma and many years later. To date, however,
      there is little literature on pseudodementia as a delayed traumatic stress
      response. The authors present a case history of a 50-year-old woman who developed
      severe cognitive impairment following retrieval of previously forgotten memories
      of childhood sexual abuse. Her cognitive condition deteriorated rapidly and
      dramatically. Neuropsychological assessment and clinical presentation led to a
      diagnosis of frontotemporal dementia (vs. corticobasal degeneration). Detailed
      neurologic and medical evaluations could not identify any underlying physical
      cause. Her condition progressively worsened over 9 months, at which point
      memantine, an N-methyl-D-aspartate receptor antagonist, was begun. The patient
      regained full functioning over the next year. Although an organic cause could not
      be ruled out, it was likely that recovery of traumatic memories was contributory
      to the patient's condition, as ongoing psychotherapy had begun 1 year into the
      course. If additional cases with similar presentations are reported, such cases
      would corroborate the notion that persistent, severe, and reversible cognitive
      impairment constitutes a previously unrecognized and atypical posttraumatic
      response. 

PMID- 25991052
TI  - Atropinic burden of prescriptions forms in patients with Alzheimer disease: a
      cross-sectional study in a French PharmacoVigilance Database.
AB  - AIM: Atropinic drugs in patients with Alzheimer disease (AD) can decrease the
      effects of anticholinesterase drugs and/or induce adverse drug reactions (ADRs).
      Several atropinic risk scales defining an atropinic burden of drugs were proposed
      but were little used in AD patients. METHODS: All ADRs' notifications of AD
      patients registered in the Midi-Pyrenees PharmacoVigilance Database between 1999
      and 2013 were analyzed using Anticholinergic Drug Scale (ADS) and Anticholinergic
      Duran's list. The primary objective was to quantify atropinic burden in AD
      patients and the secondary one to investigate associated factors. RESULTS: Among
      the 475 notifications, at least one atropinic drug was found in 282 notifications
      (59.4%) according to ADS and 214 (45.1%) according to Duran. Mean number of
      atropinics per notifications was 0.9 +/- 0.9 (ADS) and 0.7 +/- 0.9 (Duran). Mean
      atropinic burden per notifications was 1.2 +/- 1.5 (ADS) and 0.9 +/- 1.3 (Duran).
      Atropinic burden >= 3 was found in 87 notifications (18.2%) according to ADS and
      50 (10.5%) according to Duran. There was no association between atropinic burden
      and age of patients. The number of drugs is associated to a high atropinic
      burden. CONCLUSION: The present work found an association between an atropinic
      drug and an anticholinesterase agent in around 1 out of 2 AD patients and a
      clinically significant atropinic burden (>= 3) in around 1 to 2 AD patients out
      of 10. The benefit harm balance of atropinic drugs must be discussed before each
      prescription in AD patients.

PMID- 25991054
TI  - Biliary complications in pediatric liver transplantation: Incidence and
      management over a decade.
AB  - This study analyzed how features of a liver graft and the technique of biliary
      reconstruction interact to affect biliary complications in pediatric liver
      transplantation. A retrospective analysis was performed of data collected from
      2001 to 2011 in a single high-volume North American pediatric transplant center.
      The study cohort comprised 173 pediatric recipients, 75 living donor (LD) and 98
      deceased donor (DD) recipients. The median follow-up was 70 months. Twenty-nine
      (16.7%) patients suffered a biliary complication. The majority of leaks (9/12,
      75.0%) and the majority of strictures (18/22, 81.8%) were anastomotic. There was
      no difference in the rate of biliary complications associated with DD (18.4%) and
      LD (14.7%) grafts (P = 0.55). Roux-en-Y (RY) reconstruction was associated with a
      significantly lower rate of biliary complications compared to duct-to-duct
      reconstruction (13.3% versus 28.2%, respectively; P = 0.048). RY anastomosis was
      the only significant factor protecting from biliary complications in our
      population (hazard ratio, 0.30; 95% confidence interval, 0.1-0.85). The leaks
      were managed primarily by relaparotomy (10/12, 83.3%), and the majority of
      strictures were managed by percutaneous biliary intervention (14/22, 63.6%).
      Patients suffering biliary complications had inferior graft survival (P = 0.04)
      at 1, 5, and 10 years compared to patients without biliary complications. Our
      analysis demonstrates a lower incidence of biliary complications with RY biliary
      reconstruction, and patients with biliary complications have decreased graft
      survival.

PMID- 25991055
TI  - [Severe traumatic head injury].

PMID- 25991056
TI  - ["Survivors": New patient collective in anesthesia].

PMID- 25991057
TI  - [Erratum to: Implementation of a new emergency room protocol at a University
      Medical Center in Germany : Basis for improved flow of information, adequate
      quality management and scientific assessment].

PMID- 25991059
TI  - Investigating the resistance to telemedicine in Ethiopia.
AB  - BACKGROUND: Telemedicine has great potential to improve health care in Africa as
      well as other developing areas, especially when medical expertise is urgently
      needed in emergency situations. Yet resistance from healthcare professionals
      could prevent telemedicine's social value from being materialized. OBJECTIVE:
      This article intends to understand why healthcare providers resist using
      telemedicine from a threat-control perspective. METHOD: A survey on 107
      healthcare professionals in Ethiopia was conducted. CONCLUSIONS: The resistance
      to telemedicine is determined by perceived threat and perceived controllability,
      which in turn are influenced by reduced autonomy, anxiety, and costs. Government
      support weakens the effect of perceived threat but strengthens the effect of
      perceived controllability on telemedicine resistance.

PMID- 25991061
TI  - Construct validity and reliability of the Selective Control Assessment of the
      Lower Extremity in children with cerebral palsy.
AB  - AIM: Assessing impaired selective voluntary movement control in children with
      cerebral palsy (CP) has gained increasing interest. We investigated construct
      validity and intra- and interrater reliability of the Selective Control
      Assessment of the Lower Extremity (SCALE). METHOD: Thirty-nine children (21
      males, 18 females) with spastic CP, mean age 12 years 6 months [range 6y 11mo-19y
      9mo], Gross Motor Function Classification System (GMFCS) levels I to IV,
      participated. Differences in SCALE scores were determined on joint levels and
      between patients categorized according to their limb distribution and GMFCS
      levels. SCALE scores were correlated with the Fugl-Meyer Assessment, Manual
      Muscle Test, and Modified Ashworth Scale. To determine reliability, the SCALE was
      applied once and recorded on video. RESULTS: SCALE scores differed significantly
      between the less and more affected leg (p<0.001) and between most leg joints.
      Total SCALE scores differed significantly between GMFCS levels I and II.
      Correlations with Fugl-Meyer Assessment, Manual Muscle Test, and Modified
      Ashworth Scale were 0.88, 0.88, and -0.55 respectively. Intraclass correlation
      coefficients were all above 0.9, with the minimal detectable change below 2
      points. INTERPRETATION: The SCALE appears to be a valid and reliable tool to
      assess selective voluntary movement control of the legs in children with spastic
      CP.

PMID- 25991060
TI  - Associations of smoking and alcohol consumption with impaired beta-cell function
      in Chinese men.
AB  - BACKGROUND: The aims of the present study were to examine the association of
      cigarette smoking and alcohol consumption with impaired beta-cell function in
      Chinese men, particularly the interaction of smoking and alcohol consumption on
      impaired insulin secretion. METHODS: A population-based cross-sectional study was
      performed in 3957 Chinese men aged >=40 years. The homeostatic model assessment
      of beta-cell function (HOMA-beta) was calculated, and impaired beta-cell function
      was defined as less than the lowest quartile HOMA-betacut-off point. RESULTS: The
      prevalence of impaired beta-cell function in current smokers and heavy drinkers
      (>=200 g/week) was significantly higher than in non-smokers and non-drinkers,
      respectively. Compared with non-smoking, current smoking had an exacerbating
      relationship with impaired beta-cell function (odds ratio [OR] 1.78; 95%
      confidence interval [CI] 1.47-2.15; P < 0.001). No significant association was
      found between impaired beta-cell function and former smoking (P = 0.21), although
      low and heavy drinking were associated with an increased risk of impaired beta
      cell function (OR 1.40 [95% CI 1.07-1.81] and 2.14 [95% CI 1.77-2.58],
      respectively) compared with non-drinking. The combination of current smoking and
      heavy drinking was associated with the highest risk of impaired beta-cell
      function (OR 3.16; 95% CI 2.43-4.12; P < 0.0001) after adjustment for
      confounders. We did not detect an additive interaction between current smoking
      and heavy drinking on the association with impaired beta-cell function.
      CONCLUSIONS: Cigarette smoking and alcohol consumption were significantly and
      independently associated with impaired beta-cell function in Chinese men.

PMID- 25991063
TI  - Synthesis of 1,3,5-triazines via Cu(OAc)2-catalyzed aerobic oxidative coupling of
      alcohols and amidine hydrochlorides.
AB  - Cu(OAc)2 was found to be an efficient catalyst for dehydrogenative synthesis of
      1,3,5-triazine derivatives via oxidative coupling reaction of amidine
      hydrochlorides and alcohols in air. Both aromatic and aliphatic alcohols can be
      involved in the reaction and thirty-three products were obtained with good to
      excellent yields. Moreover, the use of a ligand, strong base and organic oxidant
      is unnecessary. 

PMID- 25991062
TI  - Early lethality and neuronal proteinopathy in mice expressing cytoplasm-targeted
      FUS that lacks the RNA recognition motif.
AB  - Mutations to the RNA binding protein, fused in sarcoma (FUS) occur in ~5% of
      familial ALS and FUS-positive cytoplasmic inclusions are commonly observed in
      these patients. Altered RNA metabolism is increasingly implicated in ALS, yet it
      is not understood how the specificity with which FUS interacts with RNA in the
      cytoplasm can affect its aggregation in vivo. To further understand this, we
      expressed, in mice, a form of FUS (FUS DeltaRRMcyt) that lacked the RNA
      recognition motif (RRM), thought to impart specificity to FUS-RNA interactions,
      and carried an ALS-associated point mutation, R522G, retaining the protein in the
      cytoplasm. Here we report the phenotype and results of histological assessment of
      the brain of transgenic mice expressing this isoform of FUS. Results demonstrated
      that neuronal expression of FUS DeltaRRMcyt caused early lethality often preceded
      by severe tremor. Large FUS-positive cytoplasmic inclusions were found in many
      brain neurons; however, neither neuronal loss nor neuroinflammatory response was
      observed. In conclusion, the extensive FUS proteinopathy and severe phenotype of
      these mice suggests that affecting the interactions of FUS with RNA in vivo may
      augment its aggregation in the neuronal cytoplasm and the severity of disease
      processes. 

PMID- 25991064
TI  - Risk factors for incidence and case-fatality rates of healthcare-associated
      infections: a 20-year follow-up of a hospital-based cohort.
AB  - Information is lacking on the integrated evaluation of mortality rates in
      healthcare-associated infections (HAIs). Our aim was to differentiate the risk
      factors responsible for the incidence from those for the case-fatality rates in
      association with HAIs. We therefore examined the time trends of both incidence
      and case-fatality rates over a 20-year period at a tertiary-care teaching medical
      centre in Taiwan and the mortality rate was expressed as the product of the
      incidence rate and the case-fatality rate. During the study period the overall
      mortality rate fell from 0.46 to 0.32 deaths/1000 patient-days and the incidence
      rate fell from 3.41 to 2.31/1000 patient-days, but the case-fatality rate
      increased marginally from 13.5% to 14.0%. The independent risk factors associated
      with incidence of HAIs were age, gender, infection site, admission type, and
      department of hospitalization. Significant prognostic factors for HAI case
      fatality were age, infection site, intensive care, and clinical department. We
      conclude that the decreasing trend for the HAI mortality rate was accompanied by
      a significant decline in the incidence rate and this was offset by a slightly
      increasing trend in the case-fatality rate. This deconstruction approach could
      provide further insights into the underlying complex causes of mortality for
      HAIs.

PMID- 25991065
TI  - Formulation Development of Spherical Crystal Agglomerates of Itraconazole for
      Preparation of Directly Compressible Tablets with Enhanced Bioavailability.
AB  - The objective of the present work was to formulate tablet dosage form of
      itraconazole with enhanced bioavailability. Spherical crystal agglomerates (SCA)
      of itraconazole prepared by quasi emulsification solvent diffusion method using
      Soluplus and polyethylene glycol 4000 (PEG 4000) showed increased solubility (540
      MUg/ml) in 0.1 N hydrochloric acid as compared to pure drug (12 MUg/ml). A
      Fourier transform infrared (FTIR) study indicated compatibility of drug with the
      excipients. The developed SCA were spherical with smooth surface having an
      average size of 412 MUm. The significantly improved micromeritic properties
      compared to the plain drug suggested its suitability for direct compression. The
      antifungal activity of itraconazole was retained in the SCA form as evidenced
      from the results of the disc diffusion method. The optimized SCA formulation
      could be easily compressed into tablet with desirable characteristics of hardness
      (5 kg/cm(2)) and disintegration time (6.3 min). The in vitro dissolution studies
      showed significant difference in the dissolution profiles of pure drug (21%) and
      SCA formulation (85%) which was even greater than that of marketed preparation
      (75%). In vivo pharmacokinetic showed significant enhancement in C max and AUC0-t
      with relative bioavailability of 225%. The SCA formulation seems to be promising
      for enhancement of oral bioavailability of itraconazole.

PMID- 25991066
TI  - Association of low vitamin D levels with metabolic syndrome in hemodialysis
      patients.
AB  - Low vitamin D levels have been linked to metabolic syndrome in the general
      population. In the present study, the relationship between inadequate serum
      concentrations of vitamin D and metabolic syndrome in patients with end-stage
      renal disease undergoing hemodialysis was explored. In a cross-sectional setting,
      145 patients undergoing maintenance hemodialysis were enrolled. Metabolic
      syndrome was defined using the International Diabetes Federation criteria. Serum
      concentration of 25(OH) vitamin D was determined by a commercially available
      enzyme immunosorbent assay method. The prevalence of metabolic syndrome was
      53.1%. The prevalence rate of severe vitamin D deficiency (<5 ng/mL) was 3.4%,
      mild vitamin D deficiency (5-15 ng/mL) 31.0%, vitamin D insufficiency (16-30
      ng/mL) 36.6%, and vitamin D sufficiency (>30 ng/mL) 29.0%. With the increasing
      number of metabolic abnormalities, vitamin D levels significantly decreased (P
      for trend = 0.028). Among the components of metabolic syndrome, vitamin D
      deficiency was significantly associated with central obesity (odds ratio [OR],
      95% confident interval [CI] = 2.80, 1.11-7.04, P = 0.028). A positive, but
      nonsignificant association between vitamin D deficiency and raised fasting plasma
      glucose was noted (OR, 95% CI = 2.40, 0.94-6.11, P = 0.067). Both vitamin D
      deficiency and insufficiency were significantly associated with an increased
      likelihood of having metabolic syndrome (P < 0.05). In a final model controlling
      for age, sex, and parathyroid hormone levels, vitamin D deficiency increased the
      odds of having metabolic syndrome by more than threefold (OR, 95% CI = 3.26, 1.30
      8.20, P = 0.012). Low levels of vitamin D are frequent among hemodialysis
      patients and are associated with the metabolic syndrome. 

PMID- 25991068
TI  - Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian
      cancer.
AB  - BACKGROUND: Ovarian cancer is the sixth most common cancer and seventh most
      common cause of cancer death in women world-wide. Three-quarters of women present
      when the disease has spread throughout the abdomen (stage III or IV) and
      treatment consists of a combination of debulking surgery and platinum-based
      chemotherapy. Although initial responses to chemotherapy are good, most women
      will relapse and require further chemotherapy and will eventually develop
      resistance to chemotherapy.PARP (poly (ADP-ribose) polymerase) inhibitors, are a
      novel type of medication that works by preventing cancer cells from repairing
      their DNA once they have been damaged by other chemotherapy agents. It is not
      clear how PARP inhibitors compare to conventional chemotherapy regimens for the
      treatment of ovarian cancer, with respect to survival, side effects and quality
      of life. OBJECTIVES: To determine the benefits and risks of PARP inhibitors for
      the treatment of epithelial ovarian cancer (EOC). SEARCH METHODS: We identified
      randomised controlled trials (RCTs) by searching the Cochrane Central Register of
      Controlled Trials (CENTRAL 2014, Issue 4), the Cochrane Gynaecological Cancer
      Group Trial Register, MEDLINE (1990 to May 2014), EMBASE (1990 to May 2014),
      ongoing trials on www.controlled-trials.com/rct, www.clinicaltrials.gov,
      www.cancer.gov/clinicaltrials and the National Research Register (NRR), the FDA
      database and pharmaceutical industry biomedical literature. SELECTION CRITERIA:
      Women with histologically proven EOC who were randomised to treatment groups in
      trials that either compared PARP inhibitors with no treatment, or PARP inhibitors
      versus conventional chemotherapy, or PARP inhibitors together with conventional
      chemotherapy versus conventional chemotherapy alone. DATA COLLECTION AND
      ANALYSIS: We used standard Cochrane methodology. Two review authors independently
      assessed whether studies met the inclusion criteria. We contacted investigators
      for additional data, where possible. Outcomes included survival, quality of life
      and toxicity. MAIN RESULTS: We included four RCTs involving 599 women with EOC.
      Data for veliparib were limited and of low quality, due to small numbers (75
      women total). Olaparib, on average, improved progression-free survival (PFS) when
      added to conventional treatment and when used as maintenance treatment in women
      with platinum-sensitive disease compared with placebo (hazard ratio (HR) 0.42,
      95% confidence interval (CI) 0.29 to 0.60; 426 participants ; two studies), but
      did not improve overall survival (OS) (HR 1.05, 95% CI 0.79 to 1.39; 426
      participants; two studies). We graded this evidence as moderate quality using the
      GRADE approach. Olaparib was associated with more severe adverse events (G3/4)
      during the maintenance phase compared with controls (risk ratio (RR) 1.74, 95% CI
      1.22 to 2.49; 385 participants, two studies; moderate quality evidence). Quality
      of life data were insufficient for meta-analysis. We identified four ongoing
      studies. AUTHORS' CONCLUSIONS: PARP inhibitors appear to improve PFS in women
      with recurrent platinum-sensitive disease. Ongoing studies are likely to provide
      more information about whether the improvement in PFS leads to any change in OS
      in this subgroup of women with EOC. More research is needed to determine whether
      PARP inhibitors have any role to play in platinum-resistant disease.

PMID- 25991070
TI  - Effects of Age-Related Aortic Root Anatomic Changes on Left Ventricular Outflow
      Tract Pace-Mapping Morphologies: A Cardiac Magnetic Resonance Imaging Validation
      Study.
AB  - INTRODUCTION: Outflow tract ventricular arrhythmias (OT VAs) are common and
      catheter ablation is an effective treatment option. We sought to investigate the
      relationship between age-related anatomic aortic root changes and QRS morphology
      during left ventricular outflow tract (LVOT) pace-mapping using cardiac magnetic
      resonance (CMR) imaging. METHODS AND RESULTS: Fifty-one patients undergoing CMR
      imaging were divided into 3 groups based on age (<40, 40-60, >60 years). We
      measured the angle of the aortic root, the aorta to ventricular septal angle, the
      distance between the right coronary cusp (RCC) and left coronary cusp (LCC), and
      the distance between the ascending and descending aorta. Additionally, we
      evaluated the QRS morphologies obtained during pace-mapping from the LVOT. In
      older patients, LCC was more superior to the RCC (P < 0.01). Age was positively
      correlated with the aortic root angle (r2 = 0.481, P < 0.01) as well as the
      distances between the ascending and descending aorta at a level below the arch
      (r2 = 0.569, P < 0.01). In older patients, LVOT pace-mapping (performed in 16
      patients) demonstrated higher maximal R-wave amplitude, and was greater when
      pacing from the LCC versus the RCC in lead III (1.8 +/- 0.7 vs. 1.0 +/- 0.5 mV, P
      = 0.02). CONCLUSION: The anatomy of the aortic root changes with age, and age
      related aortic root changes may affect the QRS morphology during pace-mapping.
      Understanding the potential anatomic changes that accompany aging is important to
      maximize the efficacy of catheter ablation of OT VAs.

PMID- 25991069
TI  - Shear-dependent attenuation of cellular ROS levels can suppress proinflammatory
      cytokine injury to human brain microvascular endothelial barrier properties.
AB  - The regulatory interplay between laminar shear stress and proinflammatory
      cytokines during homeostatic maintenance of the brain microvascular endothelium
      is largely undefined. We hypothesized that laminar shear could counteract the
      injurious actions of proinflammatory cytokines on human brain microvascular
      endothelial cell (HBMvEC) barrier properties, in-part through suppression of
      cellular redox signaling. For these investigations, HBMvECs were exposed to
      either shear stress (8 dynes/cm(2), 24 hours) or cytokines (tumor necrosis factor
      alpha (TNF-alpha) or interleukin-6 (IL-6), 0 to 100 ng/mL, 6 or 18 hours). Human
      brain microvascular endothelial cell 'preshearing'+/-cytokine exposure was also
      performed. Either cytokine dose-dependently decreased expression and increased
      phosphorylation (pTyr/pThr) of interendothelial occludin, claudin-5, and vascular
      endothelial-cadherin; observations directly correlating to endothelial barrier
      reduction, and in precise contrast to effects seen with shear. We further
      observed that, relative to unsheared cells, HBMvECs presheared for 24 hours
      exhibited significantly reduced reactive oxygen species production and barrier
      permeabilization in response to either TNF-alpha or IL-6 treatment. Shear also
      downregulated NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase)
      activation in HBMvECs, as manifested in the reduced expression and coassociation
      of gp91phox and p47phox. These findings lead us to conclude that physiologic
      shear can protect the brain microvascular endothelium from injurious cytokine
      effects on interendothelial junctions and barrier function by regulating the
      cellular redox state in-part through NADPH oxidase inhibition. 

PMID- 25991071
TI  - UN implores South East Asian nations to help starving migrants stranded at sea.

PMID- 25991072
TI  - INTRODUCTION OF INNOVATIVE MEDICAL DEVICES AT FRENCH UNIVERSITY HOSPITALS: AN
      OVERVIEW OF HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT INITIATIVES.
AB  - OBJECTIVES: Local health technology assessment (HTA) to determine whether new
      health technologies should be adopted is now a common practice in many healthcare
      organizations worldwide. However, little is known about hospital-based HTA
      activities in France. The objective of this study was to explore hospital-based
      HTA activities in French university hospitals and to provide a picture of
      organizational approaches to the assessment of new and innovative medical
      devices. METHODS: Eighteen semi-structured interviews with hospital pharmacists
      were conducted from October 2012 to April 2013. Six topics were discussed in
      depth: (i) the nature of the institution concerned; (ii) activities relating to
      innovative medical devices; (iii) the technology assessment and decision-making
      process; (iv) the methodology for technology assessment; (v) factors likely to
      influence decisions and (vi) suggestions for improving the current process. The
      interview data were coded, collated and analyzed statistically. RESULTS: Three
      major types of hospital-based HTA processes were identified: medical device
      committees, innovation committees, and "pharmacy & management" processes. HTA
      units had been set up to support medical device and innovation committees for
      technology assessment. Slow decision making was the main limitation to both these
      committee-based approaches. As an alternative, "pharmacy & management" processes
      emerged as a means of rapidly obtaining a formal assessment. CONCLUSIONS: This
      study provides an overview of hospital-based HTA initiatives in France. We hope
      that it will help to promote hospital-based HTA activities in France and
      discussions about ways to improve and harmonize practices, through the
      development of national guidelines and/or a French mini-HTA tool, for example.

PMID- 25991073
TI  - Response of Aphidius colemani to aphid sex pheromone varies depending on plant
      synergy and prior experience.
AB  - A critical stage in the success of a parasitoid is the ability to locate a host
      within its habitat. It is hypothesized that a series of olfactory cues may be
      involved in altering the parasitoid's movement patterns at this stage of
      foraging. This paper focuses specifically on host habitat location and host
      location and the olfactory stimuli necessary to mediate the transition between
      these stages. Firstly, we confirm the ability of the parasitoid Aphidius colemani
      to detect the aphid sex pheromone at an electrophysiological level. Following
      this we investigate the effect of the sex pheromone component (4aS,7S,7aR)
      nepetalactone on the movement patterns of A. colemani and its retention within an
      area. The key findings of this work are that A. colemani is able to detect the
      sex pheromone components, that parasitoid retention is increased by a synergy of
      nepetalactone and other host-associated cues and that foraging patterns are
      augmented by the presence of nepetalactone or experience associated with
      nepetalactone. 

PMID- 25991074
TI  - Is there a genetic correlation between general factors of intelligence and
      personality?
AB  - We tested a hypothesis that there is no genetic correlation between general
      factors of intelligence and personality, despite both having been selected for in
      human evolution. This was done using twin samples from Australia, the United
      States, the Netherlands, Great Britain, and Croatia, comprising altogether 1,748
      monozygotic and 1,329 same-sex dizygotic twin pairs. Although parameters in the
      model-fitting differed among the twin samples, the genetic correlation between
      the two general factors could be set to zero, with a better fit if the U.S.
      sample was excepted. 

PMID- 25991075
TI  - No moment wasted: the primary-care visit for adults with diabetes and low socio
      economic status.
AB  - AIM: To better understand the type and range of health issues initiated by
      patients and providers in 'high-quality' primary-care for adults with diabetes
      and low socio-economic status (SES). BACKGROUND: Although quality of care
      guidelines are straightforward, diabetes visits in primary care are often more
      complex than adhering to guidelines, especially in adults with low SES who
      experience many financial and environmental barriers to good care. METHODS: We
      conducted a qualitative study using direct observation of primary-care diabetes
      visits at an exemplar safety net practice in 2009-2010. Findings In a mainly
      African American (93%) low-income population with fair cardiovascular control
      (mean A1c 7.5%, BP 134/81 mmHg, and low-density lipoprotein cholesterol 100
      mg/dL), visits addressed a variety of bio-psychosocial health issues [median: 25
      problems/visit (range 13-32)]. Physicians most frequently initiated discussions
      about chronic diseases, prevention, and health behavior. Patients most frequently
      initiated discussions about social environment and acute symptoms followed by
      prevention and health behavior. CONCLUSIONS: Primary-care visits by diabetes
      patients with low SES address a surprising number and diversity of problems.
      Emerging new models of primary-care delivery and quality measurement should allow
      adequate time and resources to address the range of tasks necessary for
      integrating biomedical and psychosocial concerns to improve the health of socio
      economically disadvantaged patients.

PMID- 25991076
TI  - Negative differential resistance in boron nitride graphene heterostructures:
      physical mechanisms and size scaling analysis.
AB  - Hexagonal boron nitride (hBN) is drawing increasing attention as an insulator and
      substrate material to develop next generation graphene-based electronic devices.
      In this paper, we investigate the quantum transport in heterostructures
      consisting of a few atomic layers thick hBN film sandwiched between graphene
      nanoribbon electrodes. We show a gate-controllable vertical transistor exhibiting
      strong negative differential resistance (NDR) effect with multiple resonant
      peaks, which stay pronounced for various device dimensions. We find two distinct
      mechanisms that are responsible for NDR, depending on the gate and applied
      biases, in the same device. The origin of first mechanism is a Fabry-Perot like
      interference and that of the second mechanism is an in-plane wave vector matching
      when the Dirac points of the electrodes align. The hBN layers can induce an
      asymmetry in the current-voltage characteristics which can be further modulated
      by an applied bias. We find that the electron-phonon scattering suppresses the
      first mechanism whereas the second mechanism remains relatively unaffected. We
      also show that the NDR features are tunable by varying device dimensions. The NDR
      feature with multiple resonant peaks, combined with ultrafast tunneling speed
      provides prospect for the graphene-hBN-graphene heterostructure in the high
      performance electronics. 

PMID- 25991077
TI  - The long-term outcomes of alternating chemoradiotherapy for locoregionally
      advanced nasopharyngeal carcinoma: a multiinstitutional phase II study.
AB  - To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for
      patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to
      assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0
      2, 18-70 years-old, and sufficient organ function were eligible for this study.
      First, chemotherapy, consisting of 5-fluorouracil (800 mg/m(2) per 24 h on days 1
      5) and cisplatin (100 mg/m(2) per 24 h on day 6), was administered, then a wide
      field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of
      radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately.
      Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled
      in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%)
      completed the course of treatment. The overall survival and the progression-free
      survival rates at 5 years were 78.04% (95% CI: 69.1~87.0%), and 68.74% (95% CI:
      58.8~78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought
      to be promising. ALCRT will be considered to be a controlled trial to compare
      therapeutic results with those of concurrent chemoradiotherapy for NPC.

PMID- 25991078
TI  - No association between adherence to the healthy Nordic food index and
      cardiovascular disease amongst Swedish women: a cohort study.
AB  - BACKGROUND: In several intervention trials, a healthy Nordic diet showed
      beneficial effects on markers of cardiovascular disease. We investigated the
      association between a healthy Nordic diet and clinical diagnosis of
      cardiovascular disease. OBJECTIVE: Our aim was first to examine the association
      between a healthy Nordic food index (wholegrain bread, oatmeal, apples/pears,
      root vegetables, cabbages and fish) and the incidence of overall cardiovascular
      disease (ischaemic heart disease, stroke, arrhythmia, thrombosis and hypertensive
      disease), and secondly to test for possible effect modification by smoking, body
      mass index (BMI), alcohol consumption and age. METHODS: We conducted an analysis
      of data from the prospective Swedish Women's Lifestyle and Health cohort,
      including 43 310 women who completed a food frequency questionnaire in 1991-1992,
      and followed up until 31 December 2012 through Swedish registries. Hazard ratios
      (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional
      hazards models. RESULTS: During follow-up, 8383 women developed cardiovascular
      disease. We found no association between the healthy Nordic food index and
      overall cardiovascular disease risk or any of the subgroups investigated. There
      was a statistically significant interaction with smoking status (P = 0.02), with
      a beneficial effect only amongst former smokers (HR 0.96, 95% CI 0.94-0.99 per 1
      point increment). CONCLUSION: The present results do not support an association
      between a healthy Nordic food index and risk of cardiovascular disease in Swedish
      women. There was also no effect modification by alcohol intake, BMI or age. Our
      finding of an interaction with smoking status requires reproduction.

PMID- 25991079
TI  - The Effects of Job Demands and Organizational Resources through Psychological
      Need Satisfaction and Thwarting.
AB  - In Study 1, we tested a model in which two job demands (i.e., changes in tasks
      and ambiguities about work) and organizational resources (i.e., interpersonal and
      informational justice) influence work engagement through the satisfaction of
      individuals' psychological needs for autonomy, competence, and relatedness. In
      Study 2, we examined the indirect effects of the same job demands and
      organizational resources on burnout through need thwarting. We also examined the
      mediating role of organizational resources in the relationships of changes in
      tasks and ambiguities about work to need satisfaction (Study 1) and need
      thwarting (Study 2). Structural equation modeling performed on cross-sectional
      data collected from 461 workers in Study 1 and 708 employees in Study 2 provided
      support for the hypothesized models. Specifically, results revealed that changes
      in tasks and ambiguities about work have direct and indirect effects (via
      organizational resources) on psychological need satisfaction and need thwarting,
      which in turn positively predicted work engagement and burnout, respectively (p <
      .05). Research implications and study limitations are discussed. 

PMID- 25991080
TI  - Deep Brain Stimulation of the Nucleus Basalis of Meynert in Early Stage of
      Alzheimer's Dementia.

PMID- 25991081
TI  - Reducing Prejudice Through Brain Stimulation.
AB  - BACKGROUND: Social categorization and group identification are essential
      ingredients for maintaining a positive self-image that often lead to negative,
      implicit stereotypes toward members of an out-group. The medial prefrontal cortex
      (mPFC) may be a critical component in counteracting stereotypes activation.
      OBJECTIVE: Here, we assessed the causal role of the mPFC in these processes by
      non-invasive brain stimulation via transcranial direct current stimulation
      (tDCS). METHOD: Participants (n = 60) were randomly and equally assigned to
      receive anodal, cathodal, or sham stimulation over the mPFC while performing an
      Implicit Association Test (IAT): They were instructed to categorize in-group and
      out-group names and positive and negative attributes. RESULTS: Anodal
      excitability-enhancing stimulation decreased implicit biased attitudes toward out
      group members compared to excitability-diminishing cathodal and sham stimulation.
      CONCLUSIONS: These results provide evidence for a critical role of the mPFC in
      counteracting stereotypes activation. Furthermore, our results are consistent
      with previous findings showing that increasing cognitive control may overcome
      negative bias toward members of social out-groups.

PMID- 25991083
TI  - Open-label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese
      treatment-naive patients with chronic hepatitis C virus genotype 1 infection.
AB  - AIM: The safety and efficacy of the NS3/4A protease inhibitor faldaprevir in
      combination with the non-nucleoside NS5B polymerase inhibitor deleobuvir and
      ribavirin in Japanese treatment-naive patients with chronic genotype 1 hepatitis
      C virus (HCV) infection was evaluated. METHODS: In this multicenter, open-label
      phase 2 study, patients were assigned to 8 weeks of treatment with 80 mg (group
      1) or 120 mg (group 2) faldaprevir once daily (q.d.) in combination with
      deleobuvir 600 mg twice daily and weight-based ribavirin. This was followed by a
      24-week treatment with faldaprevir 120 mg q.d. in combination with peginterferon
      alpha-2a and ribavirin. The primary objective was safety; virological response at
      weeks 4 and 8 was a secondary endpoint. RESULTS: Twelve and 13 patients were
      treated in group 1 and 2, respectively; all were infected with HCV genotype 1b.
      All patients experienced a drug-related adverse event (AE). The frequency of
      individual events was generally numerically greater in group 2 than 1. The most
      common AEs were nausea (66.7%, group 1; 76.9%, group 2) and vomiting (33.3%,
      group 1; 61.5%, group 2). Virological response at weeks 4 and 8 was achieved by
      11 (91.7%) patients in group 1; in group 2, 12 (92.3%) patients achieved
      virological response at week 4 and all at week 8. All patients who achieved the
      week 8 endpoint achieved sustained virological response at week 12. CONCLUSION:
      Faldaprevir 80 or 120 mg q.d. in combination with deleobuvir and ribavirin was
      tolerable and had similar efficacy in Japanese patients with HCV genotype 1
      infection. ClinicalTrials.gov: NCT01528735.

PMID- 25991082
TI  - Does Preoperative Platelet Function Predict Bleeding in Patients Undergoing Off
      Pump Coronary Artery Bypass Surgery?
AB  - OBJECTIVE: We sought to examine the relationship between preoperative platelet
      function and perioperative bleeding in patients undergoing CABG. BACKGROUND:
      There are many ways to measure platelet aggregability. Little is known about
      their correlations with one another, or with bleeding. METHODS: We prospectively
      studied 50 patients undergoing a first isolated off-pump CABG. Thirty-four were
      exposed to a thienopyridine prior to surgery; 16 were not. Preoperative platelet
      function was measured by VerifyNow(r), TEG(r), AggreGuideTM, Plateletworks(r),
      vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and light
      transmission aggregometry. Bleeding was assessed 2 ways: drop from pre- to nadir
      postoperative hematocrit, and chest tube drainage. Correlation coefficients were
      calculated using Spearman's rank-order correlation. RESULTS: Mean age was 62
      years. Patient characteristics and surgical details were similar between the
      thienopyridine-exposed and non-exposed patients. The correlation coefficients
      between the 4 point-of-care platelet function measurements and hematocrit change
      ranged from -0.2274 to 0.2882. Only Plateletworks(r) correlated with drop in
      hematocrit (r = 0.2882, P = 0.0470). The correlation coefficients between each of
      the 4 point-of-care platelet function tests and the chest tube drainage were also
      poor, ranging from -0.3073 to 0.2272. Both AggreGuideTM (r = -0.3073, P = 0.0317)
      and VASP (r = -0.3187, P = 0.0272) were weakly but significantly correlated with
      chest tube drainage. The correlation among the 4 point-of-care platelet function
      measurements was poor, with coefficients ranging from -0.2504 to 0.1968.
      CONCLUSIONS: We observed little correlation among 4 platelet function tests, and
      between those assays and perioperative bleeding defined 2 different ways. Whether
      any of these assays should be used to guide decision making in individual
      patients is unclear.

PMID- 25991084
TI  - Pit assisted oxygen chemisorption on GaN surfaces.
AB  - A comprehensive analysis of oxygen chemisorption on epitaxial gallium nitride
      (GaN) films grown at different substrate temperatures via RF-molecular beam
      epitaxy was carried out. Photoemission (XPS and UPS) measurements were performed
      to investigate the nature of the surface oxide and corresponding changes in the
      electronic structure. It was observed that the growth of GaN films at lower
      temperatures leads to a lower amount of surface oxide and vice versa was observed
      for a higher temperature growth. The XPS core level (CL) and valence band maximum
      (VBM) positions shifted towards higher binding energies (BE) with oxide coverage
      and revealed a downward band bending. XPS valence band spectra were de-convoluted
      to understand the nature of the hybridization states. UPS analysis divulged
      higher values of electronic affinity and ionization energy for GaN films grown at
      a higher substrate temperature. The surface morphology and pit structure were
      probed via microscopic measurements (FESEM and AFM). FESEM and AFM analysis
      revealed that the film surface was covered with hexagonal pits, which played a
      significant role in oxygen chemisorption. The favourable energetics of the pits
      offered an ideal site for oxygen adsorption. Pit density and pit depth were
      observed to be important parameters that governed the surface oxide coverage. The
      contribution of surface oxide was increased with an increase in average pit
      density as well as pit depth. 

PMID- 25991086
TI  - 3rd Mediterranean Multidisciplinary Course on Iron Anemia April, 17(th)-18(th)
      2015, Rome, Italy.

PMID- 25991085
TI  - Physiotherapy effectiveness in ICU patients: Chest physiotherapy may not be the
      only explanation.

PMID- 25991087
TI  - Reducing Ethical Hazards in Knowledge Production.
AB  - This article discusses the ethics of knowledge production (KP) from a cultural
      point of view, in contrast with the more usual emphasis on the ethical issues
      facing individuals involved in KP. Here, the emphasis is on the cultural
      environment within which individuals, groups and institutions perform KP. A
      principal purpose is to suggest ways in which reliable scientific knowledge could
      be produced more efficiently. The distinction between ethical hazard and
      (un)ethical behaviour is noted. Ethical hazards cannot be eliminated but they can
      be reduced if the cultural ambience is suitable. The main suggestions for
      reducing ethical hazards in KP relate to the review process. It is argued that
      some defects of the current, largely anonymous, review process could be
      ameliorated by a process of comprehensive, open and ongoing review (COOR). This
      includes partial professionalisation of the work of reviewing. Review at several
      stages is a vital part of the long filtering that incorporates some claims into
      the canon of reliable knowledge. The review process would be an acknowledged and
      explicit part of KP--a respected, public and rewarded activity. COOR would be
      expensive but cost-effective. The costs should be built explicitly into research
      culture. Finally, the considerations about a more 'KP friendly' culture lead to
      advocacy of a 'long-term, short-term' synthesis; that is, of the synthesis of
      long-term vision, such as a more cooperative and less competitive culture, with
      incremental changes which may be implemented in the short term.

PMID- 25991091
TI  - Incidence Rate of Canonical vs. Derived Medical Terminology in Natural Language.
AB  - Medical terminology appears in the natural language in multiple forms: canonical,
      derived or inflected form. This research presents an analysis of the form in
      which medical terminology appears in Romanian and English language. The sources
      of medical language used for the study are web pages presenting medical
      information for patients and other lay users. The results show that, in English,
      medical terminology tends to appear more in canonical form while, in the case of
      Romanian, it is the opposite. This paper also presents the service that was
      created to perform this analysis. This tool is available for the general public,
      and it is designed to be easily extensible, allowing the addition of other
      languages. 

PMID- 25991092
TI  - Expertizer: a tool to assess the expert level of online health websites.
AB  - Health-related Web sites have become a primary resource to search for information
      on diseases, diagnoses or treatment options. Various Web sites offer a great
      variety of such information. However, lay people might have difficulties to
      assess whether a certain article or Web site fits their individual level of
      understandability. Hence, they might get overwhelmed with the delivered
      complexity of medical information. In this paper, we present a Web browser
      plugin, Expertizer that supports users in order to easily assess the expert level
      of textual medical Web content. The plugin communicates with a Web service, which
      leverages pre-computed classification models based on a Support Vector Machine. 

PMID- 25991088
TI  - Inward rectifier potassium current (I K1) and Kir2 composition of the zebrafish
      (Danio rerio) heart.
AB  - Electrophysiological properties and molecular background of the zebrafish (Danio
      rerio) cardiac inward rectifier current (IK1) were examined. Ventricular myocytes
      of zebrafish have a robust (-6.7 +/- 1.2 pA pF(-1) at -120 mV) strongly
      rectifying and Ba(2+)-sensitive (IC50 = 3.8 MUM) IK1. Transcripts of six Kir2
      channels (drKir2.1a, drKir2.1b, drKir2.2a, drKir2.2b, drKir2.3, and drKir2.4)
      were expressed in the zebrafish heart. drKir2.4 and drKir2.2a were the dominant
      isoforms in both the ventricle (92.9 +/- 1.5 and 6.3 +/- 1.5%) and the atrium
      (28.9 +/- 2.9 and 64.7 +/- 3.0%). The remaining four channels comprised together
      less than 1 and 7 % of the total transcripts in ventricle and atrium,
      respectively. The four main gene products (drKir2.1a, drKir2.2a, drKir2.2b,
      drKir2.4) were cloned, sequenced, and expressed in HEK cells for
      electrophysiological characterization. drKir2.1a was the most weakly rectifying
      (passed more outward current) and drKir2.2b the most strongly rectifying (passed
      less outward current) channel, whilst drKir2.2a and drKir2.4 were intermediate
      between the two. In regard to sensitivity to Ba(2+) block, drKir2.4 was the most
      sensitive (IC50 = 1.8 MUM) and drKir2.1a the least sensitive channel (IC50 = 132
      MUM). These findings indicate that the Kir2 isoform composition of the zebrafish
      heart markedly differs from that of mammalian hearts. Furthermore orthologous
      Kir2 channels (Kir2.1 and Kir2.4) of zebrafish and mammals show striking
      differences in Ba(2+)-sensitivity. Structural and functional differences needs to
      be taken into account when zebrafish is used as a model for human cardiac
      electrophysiology, cardiac diseases, and in screening cardioactive substances.

PMID- 25991093
TI  - A connecting system for cardiological lexicons.
AB  - The purpose of this paper is to present the approach and the development of a
      software application ("lexicons connecting" system) to correlate effectively and
      unambiguously the correspondence between the specialist medical vocabulary and
      the familiar medical vocabulary for the cardiovascular domain. To investigate the
      question, the idea, the design, and the implementation of such system will be
      described. To this end, firstly, a number of research methodologies will be
      examined including domain ontologies development, database design and
      implementation. Then, the following implementation methodology and its results
      are presented. Finally, an example of the application use will be depicted and
      future work will be briefly described. 

PMID- 25991094
TI  - A framework for contexual design and evaluation of health information technology.
AB  - Poor contextual fit is a significant cause of health information technology (HIT)
      implementation issues. While the need for better fit of HIT and context has been
      well described there is a shortcoming of approaches for how to do it. While the
      diversity of the contexts where HIT is used prevents us from designing HIT to fit
      all contexts, if we had better ways of understanding and modelling contexts we
      could design and evaluate HIT to better fit contexts of use. This paper addresses
      the above need by developing a framework consisting of a set of terminology and
      concepts for modelling contextual structures and behaviours to support HIT
      design. The framework provides a way of binding contextual considerations to
      allow us to better model contexts as part of HIT design and evaluation. 

PMID- 25991095
TI  - Observing health professionals' workflow patterns for diabetes care - First steps
      towards an ontology for EHR services.
AB  - Increasing the flexibility from a user-perspective and enabling a workflow based
      interaction, facilitates an easy user-friendly utilization of EHRs for healthcare
      professionals' daily work. To offer such versatile EHR-functionality, our
      approach is based on the execution of clinical workflows by means of a
      composition of semantic web-services. The backbone of such architecture is an
      ontology which enables to represent clinical workflows and facilitates the
      selection of suitable services. In this paper we present the methods and results
      after running observations of diabetes routine consultations which were conducted
      in order to identify those workflows and the relation among the included tasks.
      Mentioned workflows were first modeled by BPMN and then generalized. As a
      following step in our study, interviews will be conducted with clinical personnel
      to validate modeled workflows. 

PMID- 25991096
TI  - Discovering the role of morphology on the understanding of biomedical terminology
      by paramedical students.
AB  - The ability to learn specialized languages, such as biomedical language, requires
      not only specialized knowledge specific to this area, but also linguistic skills.
      We propose to study this hypothesis on the example of biomedical language as it
      is learned by advanced paramedical students in Algeria. Two particularities are
      to be addressed: linguistic specificities of biomedical terms and the fact that
      learning process is done in French while the native language of students is
      Arabic. We perform a questionnaire-based study through which students have to
      work on recognition and production of biomedical terms and of their components.
      Several difficulties are observed. We propose that terminology learning programs
      should strongly develop and rely on linguistic skills of students and on their
      morphological conscience. 

PMID- 25991097
TI  - Simulating realistic enough patient records.
AB  - Information systems for storing, managing and manipulating electronic medical
      records must place an emphasis on maintaining the privacy and security of those
      records. Though the design, development and testing of such systems also requires
      the use of data, the developers of these systems, rarely also their final end
      users, are unlikely to have ethical or governance approval to use real data.
      Alternative test data is commonly either randomly produced or taken from
      carefully anonymised subsets of records. In both cases there are potential
      shortcomings that can impact on the quality of the product being developed. We
      have addressed these shortcomings with a tool and methodology for efficiently
      simulating large amounts of realistic enough electronic patient records which can
      underpin the development of data-centric electronic healthcare systems. 

PMID- 25991098
TI  - From IHE Audit Trails to XES Event Logs Facilitating Process Mining.
AB  - Recently Business Intelligence approaches like process mining are applied to the
      healthcare domain. The goal of process mining is to gain process knowledge,
      compliance and room for improvement by investigating recorded event data.
      Previous approaches focused on process discovery by event data from various
      specific systems. IHE, as a globally recognized basis for healthcare information
      systems, defines in its ATNA profile how real-world events must be recorded in
      centralized event logs. The following approach presents how audit trails
      collected by the means of ATNA can be transformed to enable process mining. Using
      the standardized audit trails provides the ability to apply these methods to all
      IHE based information systems. 

PMID- 25991099
TI  - Participatory design for drug-drug interaction alerts.
AB  - The utilization of decision support systems, in the point of care, to alert drug
      drug interactions has been shown to improve quality of care. Still, the use of
      these systems has not been as expected, it is believed, because of the
      difficulties in their knowledge databases; errors in the generation of the alerts
      and the lack of a suitable design. This study expands on the development of
      alerts using participatory design techniques based on user centered design
      process. This work was undertaken in three stages (inquiry, participatory design
      and usability testing) it showed that the use of these techniques improves
      satisfaction, effectiveness and efficiency in an alert system for drug-drug
      interactions, a fact that was evident in specific situations such as the decrease
      of errors to meet the specified task, the time, the workload optimization and
      users overall satisfaction in the system. 

PMID- 25991100
TI  - Automatic extraction of numerical values from unstructured data in EHRs.
AB  - Clinical data recorded in modern EHRs are very rich, although their secondary use
      research and medical decision may be complicated (eg, missing and incorrect data,
      data spread over several clinical databases, information available only within
      unstructured narrative documents). We propose to address the issue related to the
      processing of narrative documents in order to detect and extract numerical values
      and to associate them with the corresponding concepts (or themes) and units. We
      propose to use a CRF supervised categorisation for the detection of segments
      (themes, numerical sequences and units) and a rules-based system for the
      association of these segments among them in order to build semantically
      meaningful sequences. The average results obtained are competitive (0.96
      precision, 0.78 recall, and 0.86 F-measure) and we plan to use the system with
      larger clinical data. 

PMID- 25991101
TI  - Exploring brand-name drug mentions on Twitter for pharmacovigilance.
AB  - Twitter has been proposed by several studies as a means to track public health
      trends such as influenza and Ebola outbreaks by analyzing user messages in order
      to measure different population features and interests. In this work we analyze
      the number and features of mentions on Twitter of drug brand names in order to
      explore the potential usefulness of the automated detection of drug side effects
      and drug-drug interactions on social media platforms such as Twitter. This
      information can be used for the development of predictive models for drug
      toxicity, drug-drug interactions or drug resistance. Taking into account the
      large number of drug brand mentions that we found on Twitter, it is promising as
      a tool for the detection, understanding and monitoring the way people manage
      prescribed drugs. 

PMID- 25991102
TI  - Methods for sonic representation of heart rate during exercise.
AB  - Sonic display of HR changes during exercise helps both the patient and the
      investigator to better identify the transition from rest values to "exercise"
      zone. then crossing the "attention" threshold and reaching the "alert" threshold.
      Three types of sonic display were tested, based on combinations of saccadic
      sounds, different intensities and different pitch. The results indicate a clear
      preference towards a display marking each of the four zones by a specific pitch. 

PMID- 25991103
TI  - Development of a database and processing method for detecting hematotoxicity
      adverse drug events.
AB  - Adverse events are detected by monitoring the patient's status, including blood
      test results. However, it is difficult to identify all adverse events based on
      recognition by individual doctors. We developed a system that can be used to
      detect hematotoxicity adverse events according to blood test results recorded in
      an electronic medical record system. The blood test results were graded based on
      Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood
      test results (Up, Down, Flat) were assessed according to the variation in the
      grade. The changes in the blood test and injection data were stored in a
      database. By comparing the date of injection and start and end dates of the
      change in the blood test results, adverse events related to a designated drug
      were detected. Using this method, we searched for the occurrence of serious
      adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related
      to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased
      WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and
      0.4%, respectively. This method is useful for detecting and estimating the rate
      of occurrence of hematotoxicity adverse drug events. 

PMID- 25991104
TI  - Synthesizing analytic evidence to refine care pathways.
AB  - Care pathways play significant roles in delivering evidence-based and coordinated
      care to patients with specific conditions. In order to put care pathways into
      practice, clinical institutions always need to adapt them based on local care
      settings so that the best local practices can be incorporated and used to develop
      refined pathways. However, it is knowledge-intensive and error-prone to
      incorporate various analytic insights from local data sets. In order to assist
      care pathway developers in working effectively and efficiently, we propose to
      automatically synthesize the analytical evidences derived from multiple analysis
      methods, and recommend modelling operations accordingly to derive a refined care
      pathway for a specific patient cohort. We validated our method by adapting a
      Congestive Heart Failure (CHF) Ambulatory Care Pathway for patients with
      additional condition of COPD through synthesizing the results of variation
      analysis and frequent pattern mining against patient records. 

PMID- 25991105
TI  - Content based image retrieval using local binary pattern operator and data mining
      techniques.
AB  - Content based image retrieval (CBIR) concerns the retrieval of similar images
      from image databases, using feature vectors extracted from images. These feature
      vectors globally define the visual content present in an image, defined by e.g.,
      texture, colour, shape, and spatial relations between vectors. Herein, we propose
      the definition of feature vectors using the Local Binary Pattern (LBP) operator.
      A study was performed in order to determine the optimum LBP variant for the
      general definition of image feature vectors. The chosen LBP variant is then
      subsequently used to build an ultrasound image database, and a database with
      images obtained from Wireless Capsule Endoscopy. The image indexing process is
      optimized using data clustering techniques for images belonging to the same
      class. Finally, the proposed indexing method is compared to the classical
      indexing technique, which is nowadays widely used. 

PMID- 25991106
TI  - Health consumer-oriented information retrieval.
AB  - While patients can freely access their Electronic Health Records or online health
      information, they may not be able to correctly understand the content of these
      documents. One of the challenges is related to the difference between expert and
      non-expert languages. We propose to investigate this issue within the Information
      Retrieval field. The patient queries have to be associated with the corresponding
      expert documents, that provide trustworthy information. Our approach relies on a
      state-of-the-art IR system called Indri and on semantic resources. Different
      query expansion strategies are explored. Our system shows up to 0.6740 P@10, up
      to 0.7610 R@10, and up to 0.6793 NDCG@10. 

PMID- 25991107
TI  - A methodology for mining clinical data: experiences from TRANSFoRm project.
AB  - Data mining of electronic health records (eHRs) allows us to identify patterns of
      patient data that characterize diseases and their progress and learn best
      practices for treatment and diagnosis. Clinical Prediction Rules (CPRs) are a
      form of clinical evidence that quantifies the contribution of different clinical
      data to a particular clinical outcome and help clinicians to decide the
      diagnosis, prognosis or therapeutic conduct for any given patient. The TRANSFoRm
      diagnostic support system (DSS) is based on the construction of an ontological
      repository of CPRs for diagnosis prediction in which clinical evidence is
      expressed using a unified vocabulary. This paper explains the proposed
      methodology for constructing this CPR repository, addressing algorithms and
      quality measures for filtering relevant rules. Some preliminary application
      results are also presented. 

PMID- 25991108
TI  - Use of eye-tracking technology in clinical reasoning: a systematic review.
AB  - Achieving a better understanding of the clinical reasoning process is an
      important approach to improve patient management and patient safety. Although
      clinical psychologists have used talk-aloud or stimulated recall approaches,
      these methods have biases. Recently, researchers have been exploring eye-tracking
      technology to gain "live" insight into clinicians' reasoning processes in certain
      fields of medicine (radiology, dermatology, etc.). We present a systematic review
      of eye-tracking literature used for clinical reasoning. We performed a literature
      search using the terms "eye" or "gaze tracking", "clinical" or "diagnostic
      reasoning", and "physician" in Pubmed, Embase, Psychinfo, Web of Science and ACM
      databases. Two investigators screened the abstracts, then full-text articles to
      select 10 pertinent studies. The studies evaluated medical decision making in
      four different medical domains using mostly experimental, observational
      approaches. A total of 208 participants were enrolled for the selected
      experiments. Paths for further studies are discussed that may extend the use of
      eye trackers in order to improve understanding of medical decision making. 

PMID- 25991109
TI  - Visual analytics in medical education: impacting analytical reasoning and
      decision making for quality improvement.
AB  - The medical curriculum is the main tool representing the entire undergraduate
      medical education. Due to its complexity and multilayered structure it is of
      limited use to teachers in medical education for quality improvement purposes. In
      this study we evaluated three visualizations of curriculum data from a pilot
      course, using teachers from an undergraduate medical program and applying visual
      analytics methods. We found that visual analytics can be used to positively
      impacting analytical reasoning and decision making in medical education through
      the realization of variables capable to enhance human perception and cognition on
      complex curriculum data. The positive results derived from our evaluation of a
      medical curriculum and in a small scale, signify the need to expand this method
      to an entire medical curriculum. As our approach sustains low levels of
      complexity it opens a new promising direction in medical education informatics
      research. 

PMID- 25991110
TI  - Why do we need and how can we realize a multi-disciplinary approach to health
      informatics?
AB  - Like no other area, health and social care are characterized by a multi
      disciplinary nature. This development gets even stronger by the move towards a
      personalized, predictive, preventive and participative care paradigm as well as
      by organizational and technological changes leading to highly distributed care
      setting realized by multiple stakeholder communities from different policy
      domains. Those paradigm changes result in growing interoperability challenges
      when enabling communication and cooperation of all the different actors based on
      shared knowledge and skills. For meeting those challenges, a systems-oriented,
      architecture-centric, ontology-based and policy-driven approach in health
      informatics education, but also in modeling, implementing and maintaining health
      informatics interoperability is inevitable. The paper introduces the
      aforementioned concepts. 

PMID- 25991111
TI  - Investigation of the quality and effectiveness of telemedicine in children with
      diabetes.
AB  - In the 21st century technology has rapidly evolved and has managed to eliminate
      distances, and especially in the health sector. The purpose of this study is to
      investigate the families' satisfaction and effectiveness resulted from the use of
      telehealth services that are provided to children with diabetes mellitus type 1.
      The evaluation at the individual level (user) has been done by completing two
      questionnaires. The study involved 100 parents whose children have diabetes
      mellitus type 1 (50 using telemedicine and 50 without). The majority of parents
      involved in the study, thinks that their knowledge level on telemedicine system
      is sufficient (96%) and would recommend its use to other parents whose children
      have diabetes (82%). Meanwhile, 80% evaluate the telemedicine system as adequate.

PMID- 25991112
TI  - How to use concept mapping to identify barriers and facilitators of an electronic
      quality improvement intervention.
AB  - Systematic quality improvement (QI) interventions are increasingly used to change
      complex health care systems. Results of randomized clinical trials can provide
      quantitative evidence whether QI interventions were effective but they do not
      teach us why and how QI was (not) achieved. Qualitative research methods can
      answer these questions but typically involve only a small group of respondents
      against high resources. Concept mapping methodology overcomes these drawbacks by
      integrating results from qualitative group sessions with multivariate statistical
      analysis to represent ideas of diverse stakeholders visually on maps in an
      efficient way. This paper aims to describe how to use concept mapping to
      qualitatively gain insight into barriers and facilitators of an electronic QI
      intervention and presents experiences with the method from an ongoing case study
      to evaluate a QI system in the field of cardiac rehabilitation in the
      Netherlands. 

PMID- 25991113
TI  - Insights and limits of usability evaluation methods along the health information
      technology lifecycle.
AB  - A great variety of usability evaluation methods exist but they do not provide the
      same kind of results and do not address the same stage of the Health Information
      Technology (HIT) lifecycle. This paper takes stock of the application of expert
      evaluation, usability testing, clinical simulation, clinical trials and post
      implementation surveillance to provide an overview of their main similarities and
      differences. Results from this comparison will help in choosing methods that are
      best able to evaluate a HIT and improve its usability and ultimately its safety
      of use. 

PMID- 25991114
TI  - Improvement of Diagnosis Coding by Analysing EHR and Using Rule Engine:
      Application to the Chronic Kidney Disease.
AB  - Coding medical diagnosis in case mix databases is a time-consuming task as every
      information available in patient records has to be taken into account. We
      developed rules based on EHR data with the Drools rules engine in order to
      support diagnosis coding of chronic kidney disease (CKD) in our hospital. 520
      patients had a GFR < 60 ml/min as estimated by the Cockroft-Gault formula and
      corresponded to 429 case mix database entries. We compared stays in which the
      patient was older than 12 and younger than 65 or 80 at the time of the stay. We
      concluded that our rules engine implementation may improve coding of CKD for
      45.6% of patients with a GFR < 60 ml/min and younger than 65. When patients are
      older than 65 our rule engine may be less useful for suggesting missing codes of
      CKD because the estimation of GFR by the Cockroft-Gault formula becomes less
      reliable as patients get older. 

PMID- 25991115
TI  - Multidisciplinary Modelling of Symptoms and Signs with Archetypes and SNOMED-CT
      for Clinical Decision Support.
AB  - Clinical Decision Support Systems (CDSS) help to improve health care and reduce
      costs. However, the lack of knowledge management and modelling hampers their
      maintenance and reuse. Current EHR standards and terminologies can allow the
      semantic representation of the data and knowledge of CDSS systems boosting their
      interoperability, reuse and maintenance. This paper presents the modelling
      process of respiratory conditions' symptoms and signs by a multidisciplinary team
      of clinicians and information architects with the help of openEHR, SNOMED and
      clinical information modelling tools for a CDSS. The information model of the
      CDSS was defined by means of an archetype and the knowledge model was implemented
      by means of an SNOMED-CT based ontology. 

PMID- 25991116
TI  - Auditing of SNOMED CT's Hierarchical Structure using the National Drug File -
      Reference Terminology.
AB  - With the ongoing development in the field of Medical Informatics, the
      availability of cross-references and the consistency of coverage between
      terminologies become critical requirements for clinical decision support. In this
      paper, we examine the possibility of developing a framework that highlights and
      exposes hierarchical incompatibilities between different medical terminologies in
      order to facilitate the process of achieving a sufficient level of consistency
      between terminologies. For the purpose of this research, we are working with the
      Systematized Nomenclature of Medicine--Clinical Terms (SNOMED CT) and the
      National Drug File--Reference Terminology (NDF-RT)--a clinical terminology
      focused on drugs. For discovery of inconsistencies we built an automated tool.

PMID- 25991118
TI  - Re-use of SNOMED CT subset in development of the Danish national standard for
      home care nursing problems.
AB  - SNOMED CT was chosen as reference terminology for standardisation of homecare
      nursing documentation to make reporting comparable across the 98 Danish
      municipalities. The method outlined in this paper for developing a Danish
      national homecare nursing SNOMED CT subsets is a pragmatic approach to build new
      SNOMED CT subsets drawing on existing and available SNOMED CT subsets. Combining
      this approach with awareness of hierarchical coherency in SNOMED CT subsets makes
      effective retrieval of data possible. 

PMID- 25991117
TI  - Design, development and first validation of a transcoding system from ICD-9-CM to
      ICD-10 in the IT.DRG Italian project.
AB  - In Italy, ICD-9-CM is currently used for coding health conditions at hospital
      discharge, but ICD-10 is being introduced thanks to the IT-DRG Project. In this
      project, one needed component is a set of transcoding rules and associated tools
      for easing coders work in the transition. The present paper illustrates design
      and development of those transcoding rules, and their preliminary testing on a
      subset of Italian hospital discharge data. 

PMID- 25991119
TI  - Multi-agent Architecture for the Multi-Skill Tasks Modeling at the Pediatric
      Emergency Department.
AB  - Patient journey in the Pediatric Emergency Department is a highly complex
      process. Current approaches for modeling are insufficient because they either
      focus only on the single ancillary units, or therefore do not consider the entire
      treatment process of the patients, or they do not account for the dynamics of the
      patient journey modeling. Therefore, we propose an agent based approach in which
      patients and emergency department human resources are represented as autonomous
      agents who are able to react flexible to changes and disturbances through pro
      activeness and reactiveness. The main aim of this paper is to present the overall
      design of the proposed multi-agent system, emphasizing its architecture and the
      behavior of each agent of the model. Besides, we describe inter-agent
      communication based on the agent interaction protocol to ensure cooperation
      between agents when they perform the coordination of tasks for the users. This
      work is integrated into the ANR HOST project (ANR-11-TecSan-010). 

PMID- 25991120
TI  - Clinical Decision Support using a Terminology Server to improve Patient Safety.
AB  - Clinical Decision Support Systems (CDSS) are software applications that support
      clinicians in making healthcare decisions providing relevant information for
      individual patients about their specific conditions. The lack of integration
      between CDSS and Electronic Health Record (EHR) has been identified as a
      significant barrier to CDSS development and adoption. Andalusia Healthcare Public
      System (AHPS) provides an interoperable health information infrastructure based
      on a Service Oriented Architecture (SOA) that eases CDSS implementation. This
      paper details the deployment of a CDSS jointly with the deployment of a
      Terminology Server (TS) within the AHPS infrastructure. It also explains a case
      study about the application of decision support to thromboembolism patients and
      its potential impact on improving patient safety. We will apply the inSPECt tool
      proposal to evaluate the appropriateness of alerts in this scenario. 

PMID- 25991121
TI  - Biomarkers in the ontology for general medical science.
AB  - A great deal of recent work has been devoted to the topic of biomarkers as aids
      to diagnosis, prognosis and treatment evaluation. Basing our work on the Ontology
      for General Medical Science (OGMS) and on the specifications provided by the
      Institute of Medicine (IOM), we propose definitions for biomarkers of various
      types. These definitions provide a formal representation of what biomarkers are
      in a way that allows us to remove certain ambiguities and inconsistencies in the
      documentation provided by the IOM. 

PMID- 25991122
TI  - Toward a patient safety upper level ontology.
AB  - Patient Safety (PS) standardization is the key to improve interoperability and
      expand international share of incident reporting system knowledge. By aligning
      the Patient Safety Categorial Structure (PS-CAST) to the Basic Formal Ontology
      version 2 (BFO2) upper level ontology, we aim to provide more rigor on the
      underlying organization on the one hand, and to share instances of concepts of
      categorial structure on the other hand. This alignment is a big step in the top
      down approach, to build a complete and standardized domain ontology in order to
      facilitate the basis to a WHO accepted new information model for Patient Safety. 

PMID- 25991123
TI  - Lessons learned in the generation of biomedical research datasets using Semantic
      Open Data technologies.
AB  - Biomedical research usually requires combining large volumes of data from
      multiple heterogeneous sources. Such heterogeneity makes difficult not only the
      generation of research-oriented dataset but also its exploitation. In recent
      years, the Open Data paradigm has proposed new ways for making data available in
      ways that sharing and integration are facilitated. Open Data approaches may
      pursue the generation of content readable only by humans and by both humans and
      machines, which are the ones of interest in our work. The Semantic Web provides a
      natural technological space for data integration and exploitation and offers a
      range of technologies for generating not only Open Datasets but also Linked
      Datasets, that is, open datasets linked to other open datasets. According to the
      Berners-Lee's classification, each open dataset can be given a rating between one
      and five stars attending to can be given to each dataset. In the last years, we
      have developed and applied our SWIT tool, which automates the generation of
      semantic datasets from heterogeneous data sources. SWIT produces four stars
      datasets, given that fifth one can be obtained by being the dataset linked from
      external ones. In this paper, we describe how we have applied the tool in two
      projects related to health care records and orthology data, as well as the major
      lessons learned from such efforts. 

PMID- 25991124
TI  - Semantic Interoperable Electronic Patient Records: The Unfolding of Consensus
      based Archetypes.
AB  - This paper is a status report from a large-scale openEHR-based EPR project from
      the North Norway Regional Health Authority encouraged by the unfolding of a
      national repository for openEHR archetypes. Clinicians need to engage in, and be
      responsible for the production of archetypes. The consensus processes have so far
      been challenged by a low number of active clinicians, a lack of critical
      specialties to reach consensus, and a cumbersome review process (3 or 4 review
      rounds) for each archetype. The goal is to have several clinicians from each
      specialty as a backup if one is hampered to participate. Archetypes and their
      importance for structured data and sharing of information has to become more
      visible for the clinicians through more sharpened information practice. 

PMID- 25991125
TI  - Toward a use case based classification of mobile health applications.
AB  - Smartphones are growing in number and mobile health applications (apps) are
      becoming a commonly used way for improving the quality of health and healthcare
      delivery. Health related apps are mainly centralized in Medical and
      health&fitness categories in Google and Apple app stores. However, these apps are
      not easily accessible by the users. We decided to develop a system facilitating
      the access to these apps, to increase their visibility and usability. Various use
      cases for 567 health related apps in French were identified and listed
      incrementally. UML modeling was then used to represent these use cases and their
      relationships with each other and with the potential users of these apps. Thirty
      one different use cases were found that were then regrouped into six major
      categories: consulting medical information references, communicating and/or
      sharing the information, fulfilling a contextual need, educational tools,
      managing professional activities, health related management. A classification of
      this type would highlight the real purpose and functionalities of these apps and
      offers the user to search for the right app rapidly and to find it in a non
      ambiguous context. 

PMID- 25991126
TI  - Combining Archetypes with Fast Health Interoperability Resources in Future-proof
      Health Information Systems.
AB  - Messaging standards, and specifically HL7 v2, are heavily used for the
      communication and interoperability of Health Information Systems. HL7 FHIR was
      created as an evolution of the messaging standards to achieve semantic
      interoperability. FHIR is somehow similar to other approaches like the dual model
      methodology as both are based on the precise modeling of clinical information. In
      this paper, we demonstrate how we can apply the dual model methodology to
      standards like FHIR. We show the usefulness of this approach for data
      transformation between FHIR and other specifications such as HL7 CDA, EN ISO
      13606, and openEHR. We also discuss the advantages and disadvantages of defining
      archetypes over FHIR, and the consequences and outcomes of this approach.
      Finally, we exemplify this approach by creating a testing data server that
      supports both FHIR resources and archetypes. 

PMID- 25991127
TI  - An IT Architecture for Systems Medicine.
AB  - Systems medicine aims to support treatment of complex diseases like cancer by
      integrating all available data for the disease. To provide such a decision
      support in clinical practice, a suitable IT architecture is necessary. We suggest
      a generic architecture comprised of the following three layers: data
      representation, decision support, and user interface. For the systems medicine
      research project "Clinically-applicable, omics-based assessment of survival, side
      effects, and targets in multiple myeloma" (CLIOMMICS) we developed a concrete
      instance of the generic architecture. We use i2b2 for representing the harmonized
      data. Since no deterministic model exists for multiple myeloma we use case-based
      reasoning for decision support. For clinical practice, visualizations of the
      results must be intuitive and clear. At the same time, they must communicate the
      uncertainty immanent in stochastic processes. Thus, we develop a specific user
      interface for systems medicine based on the web portal software Liferay. 

PMID- 25991128
TI  - Outcome-driven Evaluation Metrics for Treatment Recommendation Systems.
AB  - Treatment recommendation systems aim to providing clinical decision supports,
      e.g. with integration of Computerized Physician Order Entry (CPOE). One of the
      most significant issue is the quality of recommendations which needs to be
      quantified, before getting the acceptance from physicians. In computer science,
      such evaluations are typically performed by applying appropriate metrics that
      provides a comparison of different systems. However, a big challenge for
      evaluating treatment recommendation systems is that ground truth is only
      partially observed. In this paper, we propose an outcome-driven evaluation
      methodology, and present five metrics (i.e. precision, recall, accuracy, relative
      risk and odds ratio) with highlight of their statistic meanings in clinical
      context. The experimental results are based on the comparison of two well
      developed treatment recommendation systems (one is knowledge-driven and based on
      clinical practice guidelines, while the other is data-driven and based on patient
      similarity analysis), using our proposed evaluation metrics. As a conclusion,
      physicians are less prone to comply with clinical guidelines, but once following
      guideline recommendations, it is much more likely to get good outcomes than not
      following. 

PMID- 25991129
TI  - Identifying redundant and missing relations in the gene ontology.
AB  - Significant efforts have been undertaken for providing the Gene Ontology (GO) in
      a computable format as well as for enriching it with logical definitions.
      Automated approaches can thus be applied to GO for assisting its maintenance and
      for checking its internal coherence. However, inconsistencies may still remain
      within GO. In this frame, the objective of this work was to audit GO
      relationships. First, reasoning over relationships was exploited for detecting
      redundant relations existing between GO concepts. Missing necessary and
      sufficient conditions were then identified based on the compositional structure
      of the preferred names of GO concepts. More than one thousand redundant relations
      and 500 missing necessary and sufficient conditions were found. The proposed
      approach was thus successful for detecting inconsistencies within GO relations.
      The application of lexical approaches as well as the exploitation of synonyms and
      textual definitions could be useful for identifying additional necessary and
      sufficient conditions. Multiple necessary and sufficient conditions for a given
      GO concept may be indicative of inconsistencies. 

PMID- 25991130
TI  - Integrating Low-Cost Rapid Usability Testing into Agile System Development of
      Healthcare IT: A Methodological Perspective.
AB  - The development of more usable and effective healthcare information systems has
      become a critical issue. In the software industry methodologies such as agile and
      iterative development processes have emerged to lead to more effective and usable
      systems. These approaches highlight focusing on user needs and promoting
      iterative and flexible development practices. Evaluation and testing of iterative
      agile development cycles is considered an important part of the agile methodology
      and iterative processes for system design and re-design. However, the issue of
      how to effectively integrate usability testing methods into rapid and flexible
      agile design cycles has remained to be fully explored. In this paper we describe
      our application of an approach known as low-cost rapid usability testing as it
      has been applied within agile system development in healthcare. The advantages of
      the integrative approach are described, along with current methodological
      considerations. 

PMID- 25991131
TI  - Interactive resistance chair to promote strengthening exercise in older adults.
AB  - We developed a strengthening exercise support system which can be remotely
      managed and clinically supervised via internet. Older adults may potentially
      benefit from such an exercise system however functionality of this system
      requires validation before commencement of field studies in older adults. The aim
      of this study was to introduce and assess validity of a prototype
      telerehabilitation system supporting computer-assisted home-based strengthening
      exercise. The system included a resistance chair with a set of movement and
      physiologic sensors. Real-time feedback on exercise performance was displayed on
      a touch screen dashboard. Personalized exercise parameters were managed by a
      rehabilitation team via a designated telerehabilitation site. Assessment of the
      system demonstrated sufficient validity in real-time identification of exercise
      performance and cardiovascular parameters. We concluded that the interactive
      resistance chair has a potential in promoting strengthening exercise and it is
      warranted for further evaluation in community dwelling older adults. 

PMID- 25991132
TI  - Version changes in medical software: proposing minimal requirements for release
      notes and a version number convention - an operators' point of view.
AB  - Medical software--like any other software--is susceptible to errors. To avoid
      false system behaviour or attenuate its consequences, system operators need to
      know about changes in the software. The goal of this proposal is to define terms
      and minimum requirements regarding documentation for a version change from the
      operator's point of view, especially in the domain of medical software or
      software as a medical device (SaMD). The results are a classification of version
      changes (Upgrade: breaks support for a rollback to a prior version, Major Update:
      either substantial configuration or user education needed, Minor Update: minor
      configuration or user information needed, Patch: collection of (small) changes
      that require neither configuration nor user information.). Additionally, minimal
      requirements for release notes are determined and a document structure
      recommended.

PMID- 25991133
TI  - Normalized medical information visualization.
AB  - A new mark-up programming language is introduced in order to facilitate and
      improve the visualization of ISO/EN 13606 dual model-based normalized medical
      information. This is the first time that visualization of normalized medical
      information is addressed and the programming language is intended to be used by
      medical non-IT professionals. 

PMID- 25991134
TI  - META-GLARE: a shell for CIG systems.
AB  - In the last twenty years, many different approaches to deal with Computer
      Interpretable clinical Guidelines (CIGs) have been developed, each one proposing
      its own representation formalism (mostly based on the Task-Network Model)
      execution engine. We propose META-GLARE a shell for easily defining new CIG
      systems. Using META-GLARE, CIG system designers can easily define their own
      systems (basically by defining their representation language), with a minimal
      programming effort. META-GLARE is thus a flexible and powerful vehicle for
      research about CIGs, since it supports easy and fast prototyping of new CIG
      systems. 

PMID- 25991135
TI  - Enrich classifications in psychiatry with textual data: an ontology for
      psychiatry including social concepts.
AB  - We propose a modular approach to develop an ontology of psychiatry, ONTOPSYCHIA,
      based on Patient Discharges Summaries (PDS) and divided into three modules (i.e.
      social, mental disorders and treatments). We decided to take into account the
      social aspects of the patient life described in PDS to consider information such
      as family history, social environment or education. 

PMID- 25991136
TI  - Reuse of EHRs to Support Clinical Research in a Hospital of Reference.
AB  - Most hospitals have already implemented information systems and Electronic Health
      Records (EHRs), but the reuse of such data for research is still infrequent. We
      present a pilot project on the exploitation of clinical information from a
      Spanish hospital database in the context of the European Medical Information
      Framework project (EMIF). Specific use cases such as patients with diabetes
      mellitus type 2, obesity and dementia were assessed, by exploiting EHR data
      integrated from several separated clinical databases. The possibility to analyse
      the features of specific groups of patients based on their diagnosis codes can
      provide new data about relationships between different conditions that can
      contribute for decision-making, healthcare and research. 

PMID- 25991137
TI  - A new approach for cleansing geographical dataset using Levenshtein distance,
      prior knowledge and contextual information.
AB  - Epidemiological studies are necessary to take public health decisions. Their
      relevance depends on the quality of data. Doctors in continuous care collect a
      big amount of data that can be used for epidemiological purpose, but spatial data
      may be dirty; based on city names, the localization is imprecise, even more if it
      is misspelled. The only way to identify a city without ambiguity is to use its
      identifier, which can be retrieved by cleansing geographical textual data. In
      France, cities are organized in administrative zones called departments and some
      city names are shared by several cities in several departments. The clear
      identification of the department and the city name allows to deduce the city
      unique identifier and to make some spatial analysis such as epidemiological
      studies. In this paper, we propose a method to cleanse such data, using several
      steps. After having standardized the text to cleanse, we use the Levenshtein
      distance to generate a first set of propositions. Finally, the propositions are
      filtered, by removing the less likely candidates, so that it remains only one,
      which becomes the chosen city. Tested on a dataset of 9818 entries, we obtained
      89.1% of concordance, whereas the standard Levenshtein distance obtained 70.5%.
      This demonstrates that our method has better results. 

PMID- 25991138
TI  - Prediabetes and cardiovascular risk alert programs - useful tools for preventing
      diabetes mellitus and cardiovascular events in primary medicine.
AB  - We propose alert programs, made in Excel using VBA, for general practitioners, in
      order not to miss the diagnosis of prediabetes and cardiovascular risk factors
      for their patients and to improve their management. 

PMID- 25991139
TI  - Filling the gap between guideline development and formalization process - a
      requirement analysis.
AB  - Clinical guidelines are made to aid diagnosis, management and treatment of
      patients. Authoring, publishing, updating and maintaining clinical guidelines are
      time-consuming, labour-intensive and complex. Unfortunately, it is time-consuming
      to search and retrieve patient-specific recommendations in free-text documents.
      Literature is rich with methods proposed to support encoding of clinical
      guidelines into computer-interpretable formats (CIG). However, there is a lack of
      studies covering the actual guideline development and authoring. So, the
      objective of this research is to explore gap between tools and methods for
      authoring guideline content and for designing and implementing computer
      interpretable guidelines. Towards this objective, we have performed a user
      requirements analysis to arrive at a set of design recommendations. The resulting
      functionality framework can be used to design and develop authoring tools for the
      entire life-cycle of the computerized clinical guideline. 

PMID- 25991140
TI  - Electronic patient records system as a monitoring tool.
AB  - Data collected in electronic patient records (EPR) databases may be used for
      different goals besides their direct purpose - information support for medical
      staff in their everyday activities. One of the most promising spheres is a
      monitoring of various processes induced in medical facility. In our studies EPR
      serves as a basis for healthcare associated infections (HAI) surveillance system
      at neurosurgical intensive care unit. The results of HAI prospective surveillance
      using EPR are presented and discussed. 

PMID- 25991142
TI  - IANUA: a regional project for the determination of costs in HIV-infected
      patients.
AB  - HIV treatment is based on combined antiretroviral therapy (cART) which has
      substantially improved survival, thus resulting in an increase in patient life
      expectancy as well as in the cost of HIV-related medical care. Therefore, several
      cost effectiveness studies were implemented worldwide, with one specifically in
      the Liguria region (Italy), to compare the annual economic expense in this area
      for HIV services, and the related improvement in patients' health. The IANUA
      project is intended to implement both cost-effectiveness and cost-utility
      analysis, therefore data related to clinical indicators and perceived health
      status were collected, the latter using a questionnaire based on the EQ-5D-3L.
      Information about the antiretroviral drugs and the relative quantity that a
      patient withdraws from the hospital pharmacy every month were extracted from the
      regional "F-file". All data gathered were stored in the Ligurian HIV Network, a
      web platform developed by the DIBRIS - Medinfo laboratory. More than eight
      hundred questionnaires were collected, and data will be elaborated by economists
      and psychologists. The first statistical elaborations showed that, as expected,
      costs increased as the number of therapeutic lines increased. Moreover, the
      average annual costs for patients whose last CD4 values were below 200 cells/mmc
      corresponded to the maximum expense recorded, however, the cost for patients with
      final CD4 counts above 500 cells/mmc was not, as expected, the lowest found. This
      can be explained by the fact that stabilized patients, who had CD4 values below
      500 cells/mmc, did not need very expensive care, while patients with CD4 counts
      above 500 cells/mmc improved their health status thanks to cART. 

PMID- 25991143
TI  - Can eHealth Reduce Medical Expenditures of Chronic Diseases?
AB  - The objective of this research is to evaluate empirically the effectiveness of
      eHealth in Nishi-aizu Town, Fukushima Prefecture, based on a mail survey to the
      residents and their receipt data of National Health Insurance from November 2006
      to February 2007. The residents were divided into two groups, users and non
      users, and sent questionnaires to ask their characteristics or usage of the
      system. Their medical expenditures paid by National Health Insurance for five
      years from 2002 to 2006 are examined. The effects were analyzed by comparison of
      medical expenditures between users and non-users. The interests are focused on
      four chronic diseases namely heart diseases, high blood pressure, diabetes, and
      strokes. A regression analysis is employed to estimate the effect of eHealth to
      users who have these diseases and then calculate the monetary effect of eHealth
      on reduction of medical expenditures. The results are expected to be valid for
      establishment of evidence-based policy such as reimbursement from medical
      insurance to eHealth. 

PMID- 25991144
TI  - Secure public cloud platform for medical images sharing.
AB  - Cloud computing promises medical imaging services offering large storage and
      computing capabilities for limited costs. In this data outsourcing framework, one
      of the greatest issues to deal with is data security. To do so, we propose to
      secure a public cloud platform devoted to medical image sharing by defining and
      deploying a security policy so as to control various security mechanisms. This
      policy stands on a risk assessment we conducted so as to identify security
      objectives with a special interest for digital content protection. These
      objectives are addressed by means of different security mechanisms like access
      and usage control policy, partial-encryption and watermarking. 

PMID- 25991145
TI  - Implementability of stroke guidelines: a pragmatic comparison between US and
      European recommendations using eGLIA.
AB  - Due to the prevalence and severity of stroke, and the emergency of its
      management, the need of reaching a consensus towards its treatment is of prime
      importance. This paper's aim is to compare two stroke guidelines by using eGLIA
      in order to evaluate their implementability. Methods included a systematic
      assessment of the European (ESO) and American (AHA/ASA) guidelines with eGLIA and
      a review of literature and analysis of each recommendation with the program. The
      ESO performs better in Executability and Decidability, as 91.5% and 34.8% of
      recommendations show no barriers, compared to 81.0% and 14.0% in the AHA/ASA
      guidelines. On the other hand, AHA/ASA guideline have more recommendations with
      positive assessments in the Validity and Effect on the Process of Care (91.4% vs
      83.0% and 58.1% vs 25%). Results show that ESO guidelines address a wider patient
      view and that the AHA/ASA guidelines are stricter, only publishing
      recommendations with a high level of evidence; AHA/ASA guidelines are updated
      with more frequency and have a clearer sequence of action. Both guidelines show
      some contradictions, but of minor importance. The strength of this study is the
      fact that the whole guidelines were read and analysed, and, although we would
      suggest an improvement of the tool by adding an automatic statistics chart and
      clarifying some questions, it showed that eGLIA should be used whenever such a
      text is published. 

PMID- 25991146
TI  - Online Pharmaceutical Care Provision: Full-Implementation of an eHealth Service
      Using Design Science Research.
AB  - Chronic diseases are pressing health systems to introduce reforms, focused on
      primary care and multidisciplinary models. Community pharmacists have developed a
      new role, addressing pharmaceutical care and services. Information systems and
      technologies (IST) will have an important role in shaping future healthcare
      provision. However, the best way to design and implement an IST for
      pharmaceutical service provision is still an open research question. In this
      paper, we present a possible strategy based on the use of Design Science Research
      Methodology (DSRM). The application of the DSRM six stages is described, from the
      definition and characterization of the problem to the evaluation of the artefact.

PMID- 25991147
TI  - A system dynamics approach to analyze laboratory test errors.
AB  - Although many researches have been carried out to analyze laboratory test errors
      during the last decade, it still lacks a systemic view of study, especially to
      trace errors during test process and evaluate potential interventions. This study
      implements system dynamics modeling into laboratory errors to trace the
      laboratory error flows and to simulate the system behaviors while changing
      internal variable values. The change of the variables may reflect a change in
      demand or a proposed intervention. A review of literature on laboratory test
      errors was given and provided as the main data source for the system dynamics
      model. Three "what if" scenarios were selected for testing the model. System
      behaviors were observed and compared under different scenarios over a period of
      time. The results suggest system dynamics modeling has potential effectiveness of
      helping to understand laboratory errors, observe model behaviours, and provide a
      risk-free simulation experiments for possible strategies. 

PMID- 25991148
TI  - A template-based computerized instruction entry system helps the comunication
      between doctors and nurses.
AB  - In a hospital, doctors and nurses shares roles in treating admitted patients.
      Communication between them is necessary and communication errors become the
      problem in medical safety. In Japan, verbal instruction is prohibited and doctors
      write their instruction on paper instruction slips. However, because it is
      difficult to ascertain revision history and the active instructions on
      instruction slips, human errors can occur. We developed template-based
      computerized instruction entry system to reduce ward workloads and contribute to
      medical safety. Templates enable us to input the instructions easily and
      standardize the descriptions of instructions. By standardizing and combine the
      instruction into one template for one instruction item, the systems could prevent
      instructions overlap. We created sets of templates (e.g., admission set,
      preoperative set), so that doctors could enter their instructions easily.
      Instructions entered via any of the sets can be subdivided into separate items by
      the system before being submitted, and can also be changed on a per-item basis.
      The instructions were displayed as calendar form. Calendar form represents the
      instruction shift and current active instructions. We prepared 382 standardized
      instruction templates. In our system, 66% of instructions were entered via
      templates, and 34% were entered as free-text comments. Our system prevents
      communication errors between medical staff. 

PMID- 25991149
TI  - Data quality evaluation in medical database watermarking.
AB  - The use of watermarking in the protection of medical relational databases
      requires that the introduced distortion does not hinder records interpretation.
      In this paper, we present the preliminary results of a watermarked data quality
      evaluation protocol developed so as to analyze the perception the practitioner
      has of the watermark. These results show that some attributes are more
      appropriate for watermarking than others and also that incoherent or unlikely
      records resulting from careless watermarking are easily identified by an expert. 

PMID- 25991150
TI  - E-health stakeholders experiences with clinical modelling and standardizations.
AB  - Stakeholders in e-health such as governance officials, health IT-implementers and
      vendors have to co-operate to achieve the goal of a future-proof interoperable e
      health infrastructure. Co-operation requires knowledge on the responsibility and
      competences of stakeholder groups. To increase awareness on clinical modeling and
      standardization we conducted a workshop for Danish and a few Norwegian e-health
      stakeholders' and made them discuss their views on different aspects of clinical
      modeling using a theoretical model as a point of departure. Based on the model,
      we traced stakeholders' experiences. Our results showed there was a tendency that
      stakeholders were more familiar with e-health requirements than with design
      methods, clinical information models and clinical terminology as they are
      described in the scientific literature. The workshop made it possible for
      stakeholders to discuss their roles and expectations to each other. 

PMID- 25991151
TI  - An adaptive scheduling model for a multi-agent based VEPR data collection
      actions.
AB  - With the purpose of improving the access to departmental legacy information
      systems, a multi agent based Virtual Electronic Patient Record (VEPR) was
      deployed at a major Portuguese Hospital. The agent module (MAID) is in charge of
      identifying new data produced (reports), collecting and making it available
      through an integrated web interface. The deployed MAID system uses a static
      interval for checking the existence of new data, however from the gathered data
      regarding each department data production it is observable a variable rate
      throughout the day. In order to address this variability an adaptive model was
      developed and tested in a simulated environment with real data. The model takes
      in consideration the past report production profiles for determining a variable
      query frequency in order to reduce the average time to make data available
      minimizing the number of departmental requests. 

PMID- 25991152
TI  - Secondary use of structured patient data: interim results of a systematic review.
AB  - In addition to patient care, EHR data are increasingly in demand for secondary
      purposes, e.g. administration, research and enterprise resource planning. We
      conducted a systematic literature review and subsequent analysis of 85 articles
      focusing on the secondary use of structured patient records. We grounded the
      analysis on how patient records have been structured, how these structures have
      been evaluated and what are the main results achieved from the secondary use
      viewpoint. We conclude that secondary use requires complete and interoperable
      patient records, which in turn depend on better alignment of primary and
      secondary users' needs and benefits. 

PMID- 25991153
TI  - Implementing a tele-expertise system to optimise the antibiotic use and
      stewardship: The case of the Montpellier University Hospital (France).
AB  - This paper has two aims: 1) to describe the tele-expertise system implemented in
      the Montpellier University Hospital (France) in order to optimize antimicrobial
      use 2) to analyze the prescribers' adherence to this system. For the second
      purpose, an observational prospective study was conducted for 12 months. Data
      were collected from counselling advices, which were notified in the electronic
      medical records. 1386 tele-expertise actions were performed. Among them, 87% were
      made without clinical evaluation at the bedside. The prescribers' adherence rate
      to a diagnosis was 79%. For the therapeutic requests, 87% of answers were fully
      followed. The results outline how the tele-expertise system enables both
      infectious disease specialists and prescribers to make better decisions in
      particular cases. 

PMID- 25991154
TI  - Exploring User Experience of a Telehealth System for the Danish TeleCare North
      Trial.
AB  - The aim was to explore user experiences of using a telehealth system (Telekit)
      designed for the Danish TeleCare North trial. Telekit is designed for patients
      diagnosed with chronic obstructive pulmonary disease (COPD) in order to manage
      the disease and support patient empowerment. This article sums up COPD
      participants' user experiences in terms of increased sense of freedom, of
      security, of control, and greater awareness of COPD symptoms. A consecutive
      sample of sixty participants (27 women, 33 men) were recruited from the TeleCare
      North trial. At home the participants completed a non-standardised questionnaire
      while a researcher was present. The questionnaire identified their health status,
      their use of specific technologies, and their user experiences with the
      telehealth system. Results from the questionnaire indicate that the majority of
      participants (88%) considered the Telekit system as easy to use. 43 (72%)
      participants felt increased sense of security, and 37 (62%) participants felt
      increased sense of control by using the system. 30 (50%) participants felt
      greater awareness of their COPD symptoms, but only 16 (27%) participants felt
      increased freedom. The study has provided a general picture of COPD participants'
      user experiences which is important to emphasise as it has a bearing on whether a
      given implementation will be successful or not. 

PMID- 25991155
TI  - Engaging in large-scale digital health technologies and services. What factors
      hinder recruitment?
AB  - Implementing consumer oriented digital health products and services at scale is
      challenging and a range of barriers to reaching and recruiting users to these
      types of solutions can be encountered. This paper describes the experience of
      implementers with the rollout of the Delivering Assisted Living Lifestyles at
      Scale (dallas) programme. The findings are based on qualitative analysis of
      baseline and midpoint interviews and project documentation. Eight main themes
      emerged as key factors which hindered participation. These include how the dallas
      programme was designed and operationalised, constraints imposed by partnerships,
      technology, branding, and recruitment strategies, as well as challenges with the
      development cycle and organisational culture. 

PMID- 25991156
TI  - Development and trial of ePoint.telemed - An open web-based platform for home
      monitoring of chronic heart failure patients.
AB  - In North Norway no routine home telemonitoring services for chronic heart failure
      has yet been established and hence no investigations in the field have been
      published, although large distances and a sparse population are causes for extra
      public and private expenditure on travelling for patients when they make a visit
      to the hospital. In this paper we describe the ePoint.telemed platform for home
      telemonitoring of patients with chronic heart failure (CHF). The core of the
      platform is a dashboard, which is accessible through a browser window. Integrated
      with the dashboard are a blood pressure meter, a weight scale and a web-based
      patient questionnaire. The ePoint.telemed platform is a fully automatic internet
      based system meant for early warning in a CHF rehabilitation program. Unlike
      traditional remote medical technologies (RMT) building on dedicated medical
      equipment, we are applying easy-to-use personal health system (PHS) components
      geared towards the wellness and sports market. A Randomized Controlled Trial
      (RCT) has been started using the platform. 50 patients will be involved in the
      study with the aim of finding out if the home telemonitoring of CHF is clinically
      effective in Northern Norway and if it is cost-effective. 

PMID- 25991157
TI  - Mobile technology support for clinical decision in diabetic keto-acidosis
      emergency.
AB  - The main challenge of effectively managing emergencies in diabetic ketoacidosis
      (DKA) is the fine tuning of the treatment in order to re-establish the normal
      metabolic homeostasis. We propose a mobile application for clinical decision
      support in DKA emergencies (mDKA), running under Android on smart phones and
      tablet PCs. mDKA provides decision support for treatment concerning the main
      components (i.e. choice and dose of re-hydration agent, insulin, potassium or
      bicarbonate) for up to 12 hours after the diagnosis. The application underwent a
      preliminary scanty evaluation aimed at assessing its perceived usability. The
      results sustained the informal hints that mDKA's accuracy in deciding the
      treatment path was acceptable in terms of general variability of medical decision
      in DKA and brought evidence of positive attitude towards the application itself. 

PMID- 25991158
TI  - Nursing Intervention using smartphone technologies; a systematic review and meta
      analysis.
AB  - We reviewed mobile technology-based interventions in nursing and computed effect
      size of the interventions. We searched eight databases (KoreaMED, KMBASE, KISS,
      NDSL, Medline, EMBASE, Cochrane central library and CINAHL) using three sets of
      terms: mobile application, mobile app, mobile phone or smartphone; health or
      healthcare; and nursing. The study design, mobile technology, sample size and
      clinical outcomes were extracted from each study. A total of 38 studies were
      selected for review. Seven and six studies were used in meta-analyses for weight
      and fasting plasma glucose changes respectively. We found that mobile
      interventions used in nursing have different characteristics compared to those in
      other disciplines. We also found that mobile interventions in nursing led to
      significant improvement in weight and glucose control. 

PMID- 25991160
TI  - Clinical data warehousing for evidence based decision making.
AB  - Large volumes of heterogeneous health data silos pose a big challenge when
      exploring for information to allow for evidence based decision making and
      ensuring quality outcomes. In this paper, we present a proof of concept for
      adopting data warehousing technology to aggregate and analyse disparate health
      data in order to understand the impact various lifestyle factors on obesity. We
      present a practical model for data warehousing with detailed explanation which
      can be adopted similarly for studying various other health issues. 

PMID- 25991161
TI  - Using a snowflake data model and autocompletion to support diagnostic coding in
      acute care hospitals.
AB  - PURPOSE: Efficient and adequate coding is essential for all hospitals to optimize
      funding, follow activity, and perform epidemiological studies. OBJECTIVE: We
      propose an autocompletion method for optimizing diagnostic coding in acute care
      hospitals. METHODS: Using a terminology snowflake model integrating SNOMED 3.5
      and ICD-10 codes, autocompletion algorithms generate a list of diagnostic
      expressions from partial input concepts. RESULTS: A general autocompletion
      component has been developed and tested on a set of inpatient summary reports.
      Concepts expressed as strings of three or four characters return a noisy list of
      diagnostic labels or codes. Concepts expressed as groups of strings return lists
      that are semantically close to the labels present in hospital reports. The most
      pertinent information lies in the length of the expressions entered. CONCLUSION:
      Autocompletion can be a complementary tool to existing coding support systems.

PMID- 25991162
TI  - Planning, execution and monitoring of physical rehabilitation therapies with a
      robotic architecture.
AB  - Traditional methods of rehabilitation require continuous attention of therapists
      during the therapy sessions. This is a hard and expensive task in terms of time
      and effort. In many cases, the therapeutic objectives cannot be achieved due to
      the overwork or the difficulty for therapists to plan accurate sessions according
      to the medical criteria. For this purpose, a wide range of studies is opened in
      order to research new ways of rehabilitation, as in the field of social robotics.
      This work presents the current state of the THERAPIST project. Our main goal is
      to develop a cognitive architecture which provides a robot with enough autonomy
      to carry out an upper-limb rehabilitation therapy for patients with physical
      impairments, such as Cerebral Palsy and Obstetric Brachial Plexus Palsy.

PMID- 25991163
TI  - Clinical practice guidelines consistency for patients with multimorbidity: a case
      study in the management of type 2 diabetes and hypertension.
AB  - Decision support for the guideline-based management of patients with
      multimorbidity is a challenge since it relies on the combination of single
      disease clinical practice guidelines (CPGs). The aim of this work is to present a
      framework to check, at the modelling level, whether two CPGs overlap and are
      potentially inconsistent, thus requiring further reconciliation. The method
      relies on an ontological comparison of the patient profiles covered by CPGs and
      the recommended actions attached. It was applied to check the consistency of CPGs
      for the management of arterial hypertension and for the management of type 2
      diabetes. Results showed that the two CPGs had only one common patient profile,
      although more profiles were impacted through profile subsumption. In this
      specific case, recommended actions were not found inconsistent since
      antihypertensive and anti-diabetic drugs could be combined in an additive way. 

PMID- 25991164
TI  - Approach to extract billing data from medical documentation in Russia - lessons
      learned.
AB  - Lack of a proper infrastructure of health care providers leads to the breaks in
      the health care process Informatization. This results in the manifestation of
      different data entry point. The different data sets that are entered in these
      different points tend to serve the same task. However, due to the different
      qualification of staff a consistency of data cannot be preserved. The paper
      presents an approach where data is split to the different levels. 

PMID- 25991165
TI  - Integrated wireless sensor network for monitoring pregnant women.
AB  - The paper presents an integrated monitoring system for pregnant women in the
      third trimester using a mobile cardiotocograph and body sensors. The medical
      staff has a useful tool to detect abnormalities and prevent unfortunate events in
      time. The mobile cardiotocograph sends data in real time to a Smartphone that
      communicates the information in a cloud. The physician accesses the data using
      the hospital ObgGyn application. The advantage of using this system is that the
      pregnant woman can follow her pregnancy status evolution from home, and the
      physician receives alarms from the system if the data is not in normal range and
      has available information about the health status at any time and location. 

PMID- 25991166
TI  - Devising outlier-based alerts for medication orders.
AB  - Drugs are chemical substances, which can, on consumption and under certain
      conditions, be toxic and cause Adverse Drug Reactions (ADRs) in patients. This
      paper puts forth the proposition of generating a systemic alert to a clinician,
      at the time of placing a medication order for a patient, when the number of ADRs
      associated with the selected medication is significantly different from the
      number of ADRs associated with other drugs approved for the same therapeutic
      area. 

PMID- 25991167
TI  - Diagnostic imaging requisition quality when using an electronic medical record: a
      before-after study.
AB  - Diagnostic imaging requisition (DIR) content is legally constrained for care
      quality and patient safety concerns. A French national indicator, based on
      administrative and clinical data, has been introduced to monitor nationwide the
      conformity of such documents (CDIR). The purpose of this study was to assess the
      effect on CDIR of the deployment of the ORBISTM electronic medical record at the
      Tenon hospital (Paris, France). A before-after study has been carried out. A
      significant increase of CDIR, from 37.0% (n=676) to 49.1% (n=800), was observed
      (p < 10-5). Conformity of administrative criteria improved, but there was no
      statistical difference of clinical criteria conformity, despite the improvement
      of clinical history documentation (100%). Up to five different paper-based
      requisition forms were used by clinical departments in the before period. In the
      after period, only 27.1% of requisitions were ORBIS-edited with a CDIR of 66.8%
      (n=217). In both periods, CDIR was correlated to the level of standardization of
      the forms.

PMID- 25991168
TI  - Using EHRs for Heart Failure Therapy Recommendation Using Multidimensional
      Patient Similarity Analytics.
AB  - Electronic Health Records (EHRs) contain a wealth of information about an
      individual patient's diagnosis, treatment and health outcomes. This information
      can be leveraged effectively to identify patients who are similar to each for
      disease diagnosis and prognosis. In recent years, several machine learning
      methods have been proposed to assessing patient similarity, although the
      techniques have primarily focused on the use of patient diagnoses data from EHRs
      for the learning task. In this study, we develop a multidimensional patient
      similarity assessment technique that leverages multiple types of information from
      the EHR and predicts a medication plan for each new patient based on prior
      knowledge and data from similar patients. In our algorithm, patients have been
      clustered into different groups using a hierarchical clustering approach and
      subsequently have been assigned a medication plan based on the similarity index
      to the overall patient population. We evaluated the performance of our approach
      on a cohort of heart failure patients (N=1386) identified from EHR data at Mayo
      Clinic and achieved an AUC of 0.74. Our results suggest that it is feasible to
      harness population-based information from EHRs for an individual patient-specific
      assessment.

PMID- 25991169
TI  - Nurses' expectations and perceptions of a redesigned Electronic Health Record.
AB  - When a new Electronic Health Record is implemented or modifications are made, the
      full acceptance by end users depends on their expectations and perceptions about
      the possible benefits and the potential impacts on care quality. The redesign of
      an electronic nurse chart should consider the inherent characteristics of nurses'
      practice and the variables that may influence the implementation and use of the
      new chart. In this study, a qualitative method evaluated nurses' expectations and
      perceptions about the implementation impacts of a redesigned nurse chart in an
      electronic health record at Hospital Italiano de Buenos Aires. Seventy-four
      nurses participated in three operative groups. Following ground theory, three
      analytic dimensions were found: impact at work, communication and chart quality.
      In addition, time was a recurrent topic. Nurses found it difficult to think
      positively if reduction in time of documentation was not assured. 

PMID- 25991170
TI  - Mapping Russian Laboratory Terms to LOINC.
AB  - The paper presents the results of semiautomatic mapping of Russian laboratory
      terms to LOINC. Two clinics (A and B) and a laboratory service participated in
      the project. We were able to map 86% (Clinic A) and 87% (Clinic B) of laboratory
      terms. The required effort was reasonable and the price of mapping and
      maintenance was considered as relatively low. We established LOINC as a canonical
      coding method for a laboratory data exchange. This provided semantic
      interoperability for the data exchange process. 

PMID- 25991171
TI  - Managing uncertainties in the surgical scheduling.
AB  - Current surgical scheduling system has difficulties to handle unpredictable
      events or uncertainties. Source of uncertainties may come from the patient or the
      surgery itself, where several cases require immediate changes in data, such as
      when surgery delays or cancellation occurs on the same day. The study aimed to
      model the uncertainties for managing identified uncertainties during the
      continuous scheduling, framed by resilience concept to cope with the system
      fragility. In order to be able to control and adjust any changes which may affect
      the surgery schedule of the day, we provide alternatives of solution rather than
      strictly decide the best valued options. We identified dimensions of
      uncertainties and categorized them based on the resilience concept, computed the
      impact value of potentially conflicted resources as a result of schedule change.
      With the model applied, we would provide a list of most acceptable and less
      vulnerable alternatives for anesthesiologist as a scheduler to build resilience
      in the surgical scheduling. 

PMID- 25991172
TI  - Electronic whiteboards: review of the literature.
AB  - Electronic whiteboards are being introduced into hospitals to communicate real
      time patient information instantly to staff. This paper provides a preliminary
      review of the current state of evidence for the effect of electronic whiteboards
      on care processes and patient outcomes. A literature search was performed for the
      dates 1996 to 2014 on MEDLINE, EMBASE, IEEE Xplore, Science Direct, and the ACM
      Digital Library. Thirteen papers, describing 11 studies, meeting the inclusion
      criteria were identified. The majority of studies took place in the Emergency
      Department. While studies looked at the impact of electronic whiteboards on the
      process of care, there is an absence of evidence concerning impact on patient
      outcomes. There is a need for robust research measuring the impact of electronic
      whiteboards on inpatient care. 

PMID- 25991173
TI  - Evaluation of compliance with recommendations of prevention of thromboembolism in
      atrial fibrillation in the elderly, by data reuse of electronic health records.
AB  - Under-prescription of anticoagulants in the elderly with atrial fibrillation (AF)
      has been described in several studies, showing that only 15 to 44% of them
      receive anticoagulants. However, the European Society of Cardiology
      recommendations state that anticoagulants should be systematically prescribed. In
      case of refusal of the treatment by the patient, a platelet aggregation inhibitor
      should be prescribed in monotherapy or bitherapy according to the HAS-BLED
      bleeding risk score. In all the cases the patient should receive an
      antithrombotic treatment. In this work we observe the adequacy of prescription
      practices to the recommendations for AF in the elderly by data reuse on a
      monocentric observational retrospective cohort. Data of a 222 beds French
      community hospital were extracted for the year 2013. The patients aged over 75
      years and presenting AF were selected. The HAS-BLED score was calculated and the
      consistency of the prescriptions with the recommendations of the European Society
      of Cardiology was verified. Then the compliance rate to the recommendations was
      calculated. The rules detected 433 patients with AF and aged over 75 years. From
      those patients, 45% received an anticoagulant, 32.1% received platelet
      aggregation inhibitors and 22.9% did not receive any antithrombotic treatment.
      When a platelet aggregation inhibitor was prescribed the recommendation for
      bitherapy was not followed in 97% of the cases. The compliance rate to the
      recommendations was 47.8%. This work highlights a major problem of quality of the
      prescriptions in the hospital field and shows how data reuse can help describing
      this type of issues. 

PMID- 25991174
TI  - Automatic landmarks detection in breast reconstruction aesthetic assessment.
AB  - This paper addresses a fully automatic landmarks detection method for breast
      reconstruction aesthetic assessment. The set of landmarks detected are the
      supraesternal notch (SSN), armpits, nipples, and inframammary fold (IMF). These
      landmarks are commonly used in order to perform anthropometric measurements for
      aesthetic assessment. The methodological approach is based on both illumination
      and morphological analysis. The proposed method has been tested with 21 images. A
      good overall performance is observed, although several improvements must be
      achieved in order to refine the detection of nipples and SSNs. 

PMID- 25991175
TI  - A multi-method pilot evaluation of an online diabetes exercise system.
AB  - The American Diabetes Association and The European Association of The Study of
      Diabetes recommend people with Type 2 diabetes to do moderate to vigorous aerobic
      exercise for 150 min per week to avoid late diabetic complications. However, most
      people with diabetes do not follow the recommendation. Consumer health
      information technology (CHIT) might play a role in supporting behavior changes
      that promote health and well-being. A CHIT prototype of an online diabetes
      exercise system, which contained the newest research of low volume high-intensity
      interval training (HIT), was developed. To test the system we used a multi-method
      pilot evaluation that includes; interviews, paper prototyping, heuristic
      evaluation, and test with patients. The patients expressed satisfaction with HIT
      and appreciated that the system was web-based. The findings from this pilot study
      inspire to further development and evaluation of online CHIT systems to
      diabetics. 

PMID- 25991176
TI  - EpiHosp: A web-based visualization tool enabling the exploratory analysis of
      complications of implantable medical devices from a nationwide hospital database.
AB  - Administrative data can be used for the surveillance of the outcomes of
      implantable medical devices (IMDs). The objective of this work is to build a web
      based tool allowing for an exploratory analysis of time-dependent events that may
      occur after the implementation of an IMD. This tool should enable a
      pharmacoepidemiologist to explore on the fly the relationship between a given IMD
      and a potential outcome. This tool mine the French nationwide database of
      inpatient stays from 2008 to 2013. The data are preprocessed in order to optimize
      the queries. A web tool is developed in PHP, MySQL and Javascript. The user
      selects one or a group of IMD from a tree, and can filter the results using years
      and hospital names. Four result pages describe the selected inpatient stays: (1)
      temporal and demographic description, (2) a description of the geographical
      location of the hospital, (3) a description of the geographical place of
      residence of the patient and (4) a table showing the rehospitalization reasons by
      decreasing order of frequency. Then, the user can select one readmission reason
      and display dynamically the probability of readmission by mean of a Kaplan-Meier
      curve with confidence intervals. This tool enables to dynamically monitor the
      occurrence of time-dependent complications of IMD. 

PMID- 25991177
TI  - An ontology for healthcare quality indicators: challenges for semantic
      interoperability.
AB  - Semantic interoperability, a popular research area for electronic health records,
      can also be a challenge for quality indicators. We analysed attributes and
      relationships in a diverse set of over 200 healthcare quality indicators and
      created a searchable ontology. The ontology is intended to help reduce
      duplication of effort in healthcare quality monitoring. We describe issues with
      coding the indicators and specifying inclusion and exclusion criteria and propose
      some solutions. 

PMID- 25991178
TI  - Improvement of the quality of medical databases: data-mining-based prediction of
      diagnostic codes from previous patient codes.
AB  - INTRODUCTION: Diagnoses and medical procedures collected under the French system
      of information are recorded in a nationwide database, the "PMSI national
      database", which is accessible for exploitation. Quality of the data in this
      database is directly related to the quality of coding, which can be of poor
      quality. Among the proposed methods for the exploitation of health databases,
      data mining techniques are particularly interesting. Our objective is to build
      sequential rules for missing diagnoses prediction by data mining of the PMSI
      national database. METHOD: Our working sample was constructed from the national
      database for years 2007 to 2010. The information retained for rules construction
      were medical diagnoses and medical procedures. The rules were selected using a
      statistical filter, and selected rules were validated by case review based on
      medical letters, which enabled to estimate the improvement of diagnoses recoding.
      RESULTS: The work sample was made of 59,170 inpatient stays. The predicted ICD
      codes were E11 (non-insulin-dependent diabetes mellitus), I48 (atrial
      fibrillation and flutter) and I50 (heart failure).We validated three sequential
      rules with a substantial improvement of positive predictive value:
      {E11,I10,DZQM006}=>{E11} {E11,I10,I48}=>{E11} {I48,I69}=>{I48} DISCUSSION: We
      were able to extract by data mining three simple, reliable and effective
      sequential rules, with a substantial improvement in diagnoses recoding. The
      results of our study indicate the opportunity to improve the data quality of the
      national database by data mining methods.

PMID- 25991179
TI  - Blinded Anonymization: a method for evaluating cancer prevention programs under
      restrictive data protection regulations.
AB  - Evaluating cancer prevention programs requires collecting and linking data on a
      case specific level from multiple sources of the healthcare system. Therefore,
      one has to comply with data protection regulations which are restrictive in
      Germany and will likely become stricter in Europe in general. To facilitate the
      mortality evaluation of the German mammography screening program, with more than
      10 Million eligible women, we developed a method that does not require written
      individual consent and is compliant to existing privacy regulations. Our setup is
      composed of different data owners, a data collection center (DCC) and an
      evaluation center (EC). Each data owner uses a dedicated software that
      preprocesses plain-text personal identifiers (IDAT) and plaintext evaluation data
      (EDAT) in such a way that only irreversibly encrypted record assignment numbers
      (RAN) and pre-aggregated, reversibly encrypted EDAT are transmitted to the DCC.
      The DCC uses the RANs to perform a probabilistic record linkage which is based on
      an established and evaluated algorithm. For potentially identifying attributes
      within the EDAT ('quasi-identifiers'), we developed a novel process, named
      'blinded anonymization'. It allows selecting a specific generalization from the
      pre-processed and encrypted attribute aggregations, to create a new data set with
      assured k-anonymity, without using any plain-text information. The anonymized
      data is transferred to the EC where the EDAT is decrypted and used for
      evaluation. Our concept was approved by German data protection authorities. We
      implemented a prototype and tested it with more than 1.5 Million simulated
      records, containing realistically distributed IDAT. The core processes worked
      well with regard to performance parameters. We created different generalizations
      and calculated the respective suppression rates. We discuss modalities,
      implications and limitations for large data sets in the cancer registry domain,
      as well as approaches for further improvements like l-diversity and automatic
      computation of 'optimal' generalizations. 

PMID- 25991180
TI  - How to Assist Intensive Care Units in Improving Healthcare Quality. Development
      of Actionable Quality Indicators on Blood use.
AB  - Previously developed quality indicators (QIs) for the intensive care did not give
      clues for quality improvement. We will improve this by developing new QIs that
      are actionable, reliable, valid and easy to register. Using a modified RAND
      technique we developed in three rounds new QIs for blood use at Dutch intensive
      care units (ICUs). The final set of QIs will be part of the National Intensive
      Care Evaluation quality registry and evaluated in a randomized controlled trial.
      In addition, a web-based feedback tool containing strategies for quality
      improvement will be developed. With the results of this project we hope to
      improve and maintain good quality of care at the Dutch ICUs . 

PMID- 25991181
TI  - Integrated care: an Information Model for Patient Safety and Vigilance Reporting
      Systems.
AB  - Quality management information systems for safety as a whole or for specific
      vigilances share the same information types but are not interoperable. An
      international initiative tries to develop an integrated information model for
      patient safety and vigilance reporting to support a global approach of heath care
      quality. 

PMID- 25991182
TI  - Supporting in- and off-Hospital Patient Management Using a Web-based Integrated
      Software Platform.
AB  - In this paper, a Web-based software platform appropriately designed to support
      the continuity of health care information and management for both in and out of
      hospital care is presented. The system has some additional features as it is the
      formation of continuity of care records and the transmission of referral letters
      with a semantically annotated web service. The platform's Web-orientation
      provides significant advantages, allowing for easily accomplished remote access. 

PMID- 25991183
TI  - Cross-institutional document exchange system using clinical document architecture
      (CDA) with virtual printing method.
AB  - Recently one patient received care from several hospitals at around the same
      time. When the patient visited a new hospital, the new hospital's physician tried
      to get patient information the previous hospital. Thus, patient information is
      frequently exchanged between them. Many types of healthcare facilities have
      implemented an electronic medical record system, but in Japan, healthcare
      information exchange is often done by paper. In other words, after a clinical
      doctor prints a referral document and sends it to another hospital's physician,
      another hospital's doctor receives it and scans to store the EMR in his own
      hospital's system. It is a wasteful way to exchange healthcare information about
      a patient. In order to solve this problem, we have developed a cross
      institutional document exchange system using clinical document architecture (CDA)
      with a virtual printing method. 

PMID- 25991184
TI  - Using ICT to Support Individual Guidance in Health Promotion Programs for
      Increased Physical Activity.
AB  - INTRODUCTION: We report on experiences in implementing a system to support the
      individual guidance of training in health promotion programs aiming to increase
      participants' regular level of physical activity. METHODS: We used an iterative
      development approach considering data privacy and security aspects, followed by a
      phase of field testing and continuous further development. RESULTS: Our
      preliminary results comprise identified clinically relevant parameters, suitable
      data collection methods, experienced privacy and security challenges and a glance
      on our developed prototype system. DISCUSSION: We consider our results to be of
      interest for others doing related research. The most important requirements for a
      simple supporting system can be fulfilled with established solutions in the short
      run. A more adaptable and flexible system with an increased level of support in
      analysing the data, which we aim to achieve, leads to currently open research
      challenges.

PMID- 25991185
TI  - Internet-based remote consultations - general practitioner experience and
      attitudes in Norway and Germany.
AB  - The objective of the study was to identify experiences and attitudes of German
      and Norwegian general practitioners (GPs) towards Internet-based remote
      consultation solutions supporting communication between GPs and patients in the
      context of the German and Norwegian healthcare systems. METHODS: Interviews with
      four German and five Norwegian GPs were conducted. The results were qualitatively
      analyzed. RESULTS: All interviewed GPs stated they would like to make use of
      Internet-based remote consultations in the future. Current experiences with
      remote consultations are existent to a limited degree. No GP reported to use a
      comprehensive remote consultation solution. The main features GPs would like to
      see in a remote consultation solution include asynchronous exchange of text
      messages, video conferencing with text chat, scheduling of remote consultation
      appointments, secure login and data transfer and the integration of the remote
      consultation solution into the GP's EHR system.

PMID- 25991186
TI  - Telemedicine and Cooperative Remote Healthcare Services: COPD Field Trial.
AB  - The introduction of sustainable telemedicine solutions throughout Europe requires
      the development of secure, flexible and expandable systems and the evaluation of
      their operation in real-world settings such as field trials. This paper describes
      a system for a remote monitoring and care support field trial with Chronic
      Obstructive Pulmonary Disease (COPD) patients. By following a user-centred
      development and Privacy by Design approach, the needs of all involved user groups
      could be addressed, while fulfilling, at the same time, national requirements
      with emphasis in security and privacy protection. The solution covers specific
      applications and services for COPD patients and their remote care takers, but
      allows the generalization of its applicability to other patient groups. 

PMID- 25991187
TI  - Consumer sleep tracking devices: a critical review.
AB  - Consumer sleep tracking devices are widely advertised as effective means to
      monitor and manage sleep quality and to provide positive effects on overall
      heath. However objective evidence supporting these claims is not always readily
      available. The goal of this study was to perform a comprehensive review of
      available information on six representative sleep tracking devices: BodyMedia
      FIT, Fitbit Flex, Jawbone UP, Basis Band, Innovative Sleep Solutions
      SleepTracker, and Zeo Sleep Manager Pro. The review was conducted along the
      following dimensions: output metrics, theoretical frameworks, systematic
      evaluation, and FDA clearance. The review identified a critical lack of basic
      information about the devices: five out of six devices provided no supporting
      information on their sensor accuracy and four out of six devices provided no
      information on their output metrics accuracy. Only three devices were found to
      have related peer-reviewed articles. However in these articles wake detection
      accuracy was revealed to be quite low and to vary widely (BodyMedia, 49.9+/-3.6%;
      Fitbit, 19.8%; Zeo, 78.9% to 83.5%). No supporting evidence on how well tracking
      devices can help mitigate sleep loss and manage sleep disturbances in practical
      life was provided. 

PMID- 25991188
TI  - A recommender system for medical imaging diagnostic.
AB  - The large volume of data captured daily in healthcare institutions is opening new
      and great perspectives about the best ways to use it towards improving clinical
      practice. In this paper we present a context-based recommender system to support
      medical imaging diagnostic. The system relies on data mining and context-based
      retrieval techniques to automatically lookup for relevant information that may
      help physicians in the diagnostic decision. 

PMID- 25991189
TI  - The effect of pharmaceutical services-based eHealth intervention on chronic
      patient health outcomes.

PMID- 25991191
TI  - Feasibility of post-acute hip fracture telerehabilitation in older adults.
AB  - Recent studies demonstrated potential of home-based telerehabilitation in older
      adults and individuals with mobility impairment. However limited evidence exists
      on feasibility of home-based telerehabilitation in older adults after hip
      fracture. The aims of this study were: (1) to assess impact of home-based
      telerehabilitation of community dwelling older adults in post-acute phase of
      recovery after hip fracture on mobility, psycho-behavioral factors, quality of
      life, and satisfaction with care; (2) to estimate acceptance of the
      telerehabilitation system and adherence to the exercise program. We found
      statistically significant improvements in exercise self-efficacy, mobility,
      quality of life, and patient satisfaction after 30-day hip fracture
      telerehabilitation. Home telerehabilitation may be a viable model for post-acute
      hip fracture recovery and it is warranted for further evaluation in clinical
      trials. 

PMID- 25991192
TI  - Multimedia Health Records: user-centered design approach for a multimedia
      uploading service.
AB  - Multimedia elements add value to text documents by transmitting information
      difficult to express in words. In healthcare, many professional and services keep
      this elements in their own repositories. This brings the problem of information
      fragmentation in different silos which hinder its access to other healthcare
      professionals. On the other hand patients have clinical data of their own in
      different formats generated in different healthcare organizations which is not
      accessible to professionals within our healthcare network. This paper describes
      the design, development and implementation processes of a service which allows
      media elements to be loaded in a patient clinical data repository (CDR) either
      through an electronic health record by professionals (EHR) or through a personal
      health record (PHR) by patients, in order to avoid fragmentation of the
      information. 

PMID- 25991193
TI  - Tablet Technology for Rehabilitation after Spinal Cord Injury: a Proof-of
      Concept.
AB  - Spinal cord injury (SCI) is a damage to the spinal cord resulting in a change,
      either temporary or permanent, in motor, sensory, or autonomic functions.
      Patients with SCI usually have permanent and often devastating neurologic
      deficits and disability. Trunk motor control is crucial for postural stability
      and propulsion after low thoracic SCI and several rehabilitative strategies are
      aimed at trunk stability and control. Tablet technology and gaming systems are
      novel and potentially useful strategies that apply relevant concepts in
      rehabilitation for these patients. In this study we combined the traditional
      training of trunk control with exercises administered through two iPad games
      apps, 2 or 3 times a week. All the participant patients showed increasing game
      scores during the treatment, as well as increasing Trunk Recovery Scale scores,
      showing a significant improvement in trunk control. Also the personal judgment of
      the patients, collected through evaluation questionnaires, was very positive. 

PMID- 25991194
TI  - Dynamic feature selection applied to the recognition of grasping movements in the
      control of bioprosthetic hand.
AB  - The paper presents novel method of dynamic feature selection (DFS) and its
      application in the problem of recognition of patient intent in the bioprosthesis
      control system. In the proposed approach features are selected dynamically, i.e.
      separately for each classified object according to the local value of usability
      measure of primary features. The usability measure is determined in the
      supervised learning procedure using randomized reference model. The performance
      of the DFS method was experimentally compared with four other feature selection
      algorithms. The approach developed achieved the highest classification accuracy
      demonstrating the potential of the DSF method for the control of bioprosthetic
      hand. 

PMID- 25991195
TI  - A Kinect based intelligent e-rehabilitation system in physical therapy.
AB  - This paper presents an intelligent Kinect and fuzzy inference system based e
      rehabilitation system. The Kinect can detect the posture and motion of the
      patients while the fuzzy inference system can interpret the acquired data on the
      cognitive level. The system is capable to assess the initial posture and motion
      ranges of 20 joints. Using angles to describe the motion of the joints, exercise
      patterns can be developed for each patient. Using the exercise descriptors the
      fuzzy inference system can track the patient and deliver real-time feedback to
      maximize the efficiency of the rehabilitation. The first laboratory tests confirm
      the utility of this system for the initial posture detection, motion range and
      exercise tracking. 

PMID- 25991196
TI  - AUVA - Augmented Reality Empowers Visual Analytics to explore Medical Curriculum
      Data.
AB  - Medical curriculum data play a key role in the structure and the organization of
      medical programs in Universities around the world. The effective processing and
      usage of these data may improve the educational environment of medical students.
      As a consequence, the new generation of health professionals would have improved
      skills from the previous ones. This study introduces the process of enhancing
      curriculum data by the use of augmented reality technology as a management and
      presentation tool. The final goal is to enrich the information presented from a
      visual analytics approach applied on medical curriculum data and to sustain low
      levels of complexity of understanding these data. 

PMID- 25991198
TI  - End-user expectations during an electronic health record implementation: a case
      study in two academic hospitals.
AB  - Implementing an Electronic Health Record (EHR) is a sociotechnical process. End
      users' expectations and attitudes need to be monitored during the implementation
      of a new EHR. It is not clear what end-users consider the most important
      determinants (both barriers and enablers for a successful EHR implementation)
      during this process. Based on the concept mapping method and a literature search
      we developed a questionnaire to investigate which determinants (future) end-users
      of an EHR consider important. Additionally we analysed whether there are
      differences between a centre working with a legacy EHR and one with paper-based
      patient records before implementation. We identified the following determinants:
      usability of EHR, availability of facilities, alignment with work processes,
      support during implementation, training on new EHR, support after implementation,
      practice with new EHR, internal communication, learning from other centres, reuse
      of patient data, general IT skills, and patient involvement in decision making.
      All determinants were perceived important by end-users to successfully work with
      an EHR directly after its go-live. The only two significant differences between
      centres were knowledge about the effect of the EHR on work processes, and
      importance of patient involvement in decision making. 

PMID- 25991199
TI  - A European inventory of data elements for patient recruitment.
AB  - INTRODUCTION: In the last few years much work has been conducted in creating
      systems that support clinical trials for example by utilizing electronic health
      record data. One of these endeavours is the Electronic Health Record for Clinical
      Research project (EHR4CR). An unanswered question that the project aims to answer
      is which data elements are most commonly required for patient recruitment.
      METHODS: Free text eligibility criteria from 40 studies were analysed, simplified
      and elements were extracted. These elements where then added to an existing
      inventory of data elements for protocol feasibility. RESULTS: We simplified and
      extracted data elements from 40 trials, which resulted in 1170 elements. From
      these we created an inventory of 150 unique data elements relevant for patient
      identification and recruitment with definitions and referenced codes to standard
      terminologies. DISCUSSION: Our list was created with expertise from
      pharmaceutical companies. Comparisons with related work shows that identified
      concepts are similar. An evaluation of the availability of these elements in
      electronic health records is still ongoing. Hospitals that want to engage in re
      use of electronic health record data for research purposes, for example by
      joining networks like EHR4CR, can now prioritize their effort based on this list.

PMID- 25991200
TI  - OPTIMED Platform: Curriculum Harmonisation System for Medical and Healthcare
      Education.
AB  - This contribution introduces a new web-based OPTIMED platform for an effective
      harmonisation of medical and healthcare curriculum. Behind the engineering
      background stays an original methodology covering planning model based on formal
      parameterisation of curriculum, which fully support the outcome-based approach to
      education. With the use of developed system curriculum, designers and senior
      guarantors can provide a clear and transparent composition of compulsory and
      optional courses, and easily identify potential duplicities and overlaps across a
      domain of medical and healthcare education. For students, it means an absolutely
      new way of how to understand what is really taught during a learning period,
      including all necessary meta information. All members across the academic
      community are able to search and consequently display in detail the most
      important domains related to the particular year, term, course, medical
      discipline or topic. The presented solution significantly enhances the
      transparency and continuity of the environment in which the authors of the
      teaching materials as well as their consumers work daily. Suggestions for future
      improvements of the OPTIMED platform are discussed. 

PMID- 25991201
TI  - Comparing video and avatar technology for a health education application for deaf
      people.
AB  - The article describes the steps and results of a parallel research investigating
      e-health systems design and implementation for deaf people both in avatar and
      video technology. The application translates medical knowledge and concepts in
      deaf sign language for impaired users through an avatar. Two types of avatar
      technologies are taken into consideration: Video Avatar with recorded humans
      interface and Animated Avatar with animated figure interface. The comparative
      study investigates the data collection, design, implementation and the impact
      study. The comparative analysis of video and animated technology for data
      collection shows that the video format editing requires fewer skills and results
      are obtained easier, quicker and less expensive. The video technology supports an
      easier to design and implement architecture. The impact study for 2 deaf students
      communities is under development and for the time being the video avatar is
      better perceived. 

PMID- 25991202
TI  - Requirements for a patient recruitment system.
AB  - Computerization and increasing need for evidence based medicine are not stopping
      at biomedical research. Clinical trials need participants and the problem of
      matching patients with eligibility criteria to support clinical trials has many
      different solutions. A detailed analysis of stakeholders' requirements would help
      implementing better patient recruitment systems (PRSs) in the future. Thus we
      decided to analyse the requirements in literature and talk to stakeholders what
      they feel the features of PRSs should be. Including patients and data privacy
      officers as stakeholders gives a holistic overview. Requirements are overlapping
      between different stakeholders with each stakeholder adding a different view on
      PRSs. Requirements implemented in current PRSs overlap mostly with requirements
      expressed by physicians and researchers. Especially patients' requirements (e.g.
      not having to enter medical data themselves) on PRSs give the impression that
      PRSs need to integrate with EHR systems or even PEHRs. 

PMID- 25991203
TI  - Evaluation of Internet Social Networks using Net scoring Tool: A Case Study in
      Adverse Drug Reaction Mining.
AB  - BACKGROUND AND OBJECTIVES: Suspected adverse drug reactions (ADR) reported by
      patients through social media can be a complementary tool to already existing
      ADRs signal detection processes. However, several studies have shown that the
      quality of medical information published online varies drastically whatever the
      health topic addressed. The aim of this study is to use an existing rating tool
      on a set of social network web sites in order to assess the capabilities of these
      tools to guide experts for selecting the most adapted social network web site to
      mine ADRs. METHODS: First, we reviewed and rated 132 Internet forums and social
      networks according to three major criteria: the number of visits, the notoriety
      of the forum and the number of messages posted in relation with health and drug
      therapy. Second, the pharmacist reviewed the topic-oriented message boards with a
      small number of drug names to ensure that they were not off topic. Six experts
      have been chosen to assess the selected internet forums using a French scoring
      tool: Net scoring. Three different scores and the agreement between experts
      according to each set of scores using weighted kappa pooled using mean have been
      computed. RESULTS: Three internet forums were chosen at the end of the selection
      step. Some criteria get high score (scores 3-4) no matter the website evaluated
      like accessibility (45-46) or design (34-36), at the opposite some criteria
      always have bad scores like quantitative (40-42) and ethical aspect (43-44),
      hyperlinks actualization (30-33). Kappa were positives but very small which
      corresponds to a weak agreement between experts. CONCLUSION: The personal opinion
      of the expert seems to have a major impact, undermining the relevance of the
      criterion. Our future work is to collect results given by this evaluation grid
      and proposes a new scoring tool for Internet social networks assessment.

PMID- 25991204
TI  - Understanding the Perceived Usefulness and the Ease of Use of a Hospital
      Information System: the case of a French University Hospital.
AB  - The goal of this study was to examine the perceived usefulness and the perceived
      ease of use of a Hospital Information System (HIS) for the care staff. We
      administrated a questionnaire composed of open-end and closed questions. As
      results, the perceived usefulness and ease of use are correlated with medical
      occupations. Content analysis of open questions highlights three factors
      influencing these constructs: ergonomics, errors in the documenting process and
      insufficient compatibility with the medical department or the occupation. While
      the results are consistent with literature, they show medical occupations do not
      report the same low rate of perceived usefulness and of ease of use. The main
      explanation consists in the medical risk in the prescription process for
      anesthesiologists, surgeons and physicians. 

PMID- 25991205
TI  - Health Information Systems: evaluation and performance of a Help Desk.
AB  - A Help Desk (HD) is crucial in a computerized hospital. OBJECTIVE: to describe
      the performance of a HD. DESIGN: retrospective cohort study. RESULTS: the
      sociodemographic characteristics of users, as well as their relationship with the
      institution influence behaviour when requesting support to a HD. Also we observed
      a relationship between the flow of users request and the functioning of hospital
      services. CONCLUSIONS: complexity of HD process realizes the need to identify and
      define standards to ensure quality of service.

PMID- 25991206
TI  - Problem Solving for Volatilizing Situation in Nursing: Developing Thinking
      Process Supporting System using NursingNAVI(r) Contents.
AB  - We have identified three foci of the nursing observation and nursing action
      respectively. Using these frameworks, we have developed the structured knowledge
      model for a number of diseases and medical interventions. We developed this
      structure based NursingNAVI(r) contents collaborated with some quality centered
      hospitals. Authors analysed the nursing care documentations of post-gastrectomy
      patients in light of the standardized nursing care plan in the "NursingNAVI(r)"
      developed by ourselves and revealed the "failure to observe" and "failure to
      document", which leaded to the volatility of the patients' data, conditions and
      some situation. This phenomenon should have been avoided if nurses had employed a
      standardized nursing care plan. So, we developed thinking process support system
      for planning, delivering, recording and evaluating in daily nursing using
      NursingNAVI(r) contents. A hospital decided to use NursingNAVI(r) contents in
      HIS. It was suggested that the system has availability for nursing OJT and time
      reduction of planning and recording without volatilizing situation.

PMID- 25991207
TI  - Challenges of stimulating a market for social innovation - provision of a
      national health account.
AB  - Innovation in healthcare can be associated with social innovation and the mission
      to contribute to a shared value that benefits not only individuals or
      organizations but the society as a whole. In this paper, we present the
      prerequisites of stimulating a market for social innovations by studying the
      introduction of a national health account. The results show that there is a need
      to clarify if a national health account should be viewed as a public good or not,
      to clarify the financial responsibilities of different actors, to establish clear
      guidelines and to develop regulations concerning price, quality and certification
      of actors. The ambition to stimulate the market through a national health account
      is a promising start. However, the challenges have to be confronted in order for
      public and private actors to collaborate and build a market for social
      innovations such as a national health account. 

PMID- 25991208
TI  - Competence assessment of centres participating in clinical trials.
AB  - Procedures tested in clinical trials require adequate competence of one or more
      health professionals and an adequate environment of care. In the context of
      clinical trials, it is usually not possible to separate the effect of treatments
      studied from the effect of the proficiency levels. This work proposes a method to
      assess not individual proficiency but practice performance of centres
      participating in clinical trials. We used the LC-CUSUM test to retrospectively
      assess centres' proficiency. We were finally able to ascertain one date for each
      centres from which they were considered as proficient. In conclusion, LC-CUSUM
      test seems suitable for centre's performance assessment to avoid potential bias
      in analyses due to suboptimal achievements of studied procedures. Prospective
      proficiency analyses could also be considered in a preliminary stage to standard
      clinical trials. 

PMID- 25991209
TI  - Development of Knowledge Profiles for International eHealth eLearning Courses.
AB  - Professionals working in the multidisciplinary field of eHealth vary in their
      educational background. However, knowledge in the areas of medicine, engineering
      and management is required to fulfil the tasks associated with eHealth
      sufficiently. Based on the results of an analysis of national and international
      educational offers a survey gathering user requirements for the development of
      knowledge profiles in eHealth was conducted (n=75) by professionals and students.
      During a workshop the first results were presented and discussed together with
      the network partners and the attendees. The resulting knowledge profiles contain
      knowledge areas of all three thematic content categories including fundamentals
      of medical terminology, standards and interoperability and usability as well as
      basics of all three content categories. The knowledge profiles are currently
      applied in a master's degree programme at the UAS Technikum Wien and will be
      developed further. 

PMID- 25991210
TI  - Analysis of EU-USA cooperation opportunities on IT skills for healthcare
      workforce.
AB  - An overview about the state of the art about IT skills education for the
      healthcare workforce in the EU and USA, making a specific analysis about the
      current educational programmes from different perspectives (technologies, users,
      IT skills, policies) is presented. Main result of this paper is a recommendation
      plan to address current needs on the field. Authors end with a set of conclusions
      and references that can provide the background enough for any reader interested
      on these subjects, creating awareness about the importance of transnational IT
      educational programmes for the EU-US healthcare workforce. 

PMID- 25991212
TI  - A WSN healthcare monitoring system for elderly people in geriatric facilities.
AB  - This paper investigates an enhanced WSN based monitoring system for elderly
      people in geriatric facilities. Apart from general physical monitoring
      functionalities, we explore the potential of using a wireless audio module to
      perform mental health monitoring. The telephone version of the mini mental status
      examination (T-MMSE) was adopted in the mental health monitoring and the RSSI
      (Received Signal Strength Indicator) localization algorithm was implemented in
      this system to track elderly people's the real-time location and send alerts
      based on their inactivity/activity levels, movement history and entry into
      restricted zones. Experimental test was performed to evaluate the performance of
      the proposed system. With results obtained and studied, this work can be extended
      to perform detection and rehabilitation function for elderly people with mental
      illness. This kind of monitoring system would be expected to make an important
      impact on many application scenarios for geriatric facilities. 

PMID- 25991213
TI  - Assisting e-patients in an Ask the Doctor Service.
AB  - Ask the doctor services are personalized forums allowing patients to ask
      questions directly to doctors. Usually, patients must choose the most appropriate
      category for their question among lots of categories to be redirected to the most
      relevant physician. However, manual selection is tedious and error prone
      activity. In this work we propose to assist the patients in this task by
      recommending a short list of most appropriate categories. 

PMID- 25991214
TI  - Metadata requirements for portals.
AB  - Consensus around the requirements for metadata in patient and clinical portals
      would provide a sound basis for the adoption of standards. We propose a set of
      requirements for metadata in a way that is generic and platform independent.
      These requirements cover both Clinical Documents and Clinical Statements,
      addressing the what, who, when and where of each item. 

PMID- 25991215
TI  - Citizen Personas: Exploring Challenges of Citizen-Centric eHealth.
AB  - Within the field of eHealth, there is a shift towards a patient perspective.
      However, the focus on the patient often fails to acknowledge and achieve a
      citizen-centric perspective because there is a lack of understanding of the
      context and complexities of the person and her relations, interests and
      activities. In this paper we use the persona of 'Citizen Hanne' for two purposes.
      Firstly, to highlight and provide detail in the understanding of the citizen
      perspective and thereby facilitate a shift towards a citizen-centric perspective,
      which is advanced by many in the field of eHealth. Secondly, we want to further
      nourish a critical goal of highlighting the challenges in doing citizen-centric
      eHealth and pointing out the barriers for reaching this goal. 

PMID- 25991216
TI  - Internet of things for an age-friendly healthcare.
AB  - In healthcare applications a large cohort of recent implementations utilises IoT
      oriented infrastructures (XMPP) as well as smart mobile devices as communication
      gateways. IoT characteristi Communication/Connectivity, Pervasive Computing and
      Ambient Intelligence, are all highly related to Active and Healthy Aging
      environments. This paper presents a new idea, that of IoT enabled devices which
      are directly connected to the IoT (a glucose meter is used as an example herein),
      complying with the XMPP messaging protocol and the incorporation of a recently
      released Controller Application Communication (CAC) framework for distributed,
      cross-platform communication. A web based exergaming platform and a disease
      management tool, provide the vehicles for the demonstration of the feasibility
      and the successful implementation and integration of the aforementioned
      infrastructure. 

PMID- 25991217
TI  - Contextual cloud-based service oriented architecture for clinical workflow.
AB  - Given that acceptance of systems within the healthcare domain multiple papers
      highlighted the importance of integrating tools with the clinical workflow. This
      paper analyse how clinical context management could be deployed in order to
      promote the adoption of cloud advanced services and within the clinical workflow.
      This deployment will be able to be integrated with the eHealth European
      Interoperability Framework promoted specifications. Throughout this paper, it is
      proposed a cloud-based service-oriented architecture. This architecture will
      implement a context management system aligned with the HL7 standard known as
      CCOW. 

PMID- 25991218
TI  - Acquisition of Character Translation Rules for Supporting SNOMED CT
      Localizations.
AB  - Translating huge medical terminologies like SNOMED CT is costly and time
      consuming. We present a methodology that acquires substring substitution rules
      for single words, based on the known similarity between medical words and their
      translations, due to their common Latin / Greek origin. Character translation
      rules are automatically acquired from pairs of English words and their automated
      translations to German. Using a training set with single words extracted from
      SNOMED CT as input we obtained a list of 268 translation rules. The evaluation of
      these rules improved the translation of 60% of words compared to Google Translate
      and 55% of translated words that exactly match the right translations. On a
      subset of words where machine translation had failed, our method improves
      translation in 56% of cases, with 27% exactly matching the gold standard. 

PMID- 25991219
TI  - Development of Hypertension Management Mobile Application based on Clinical
      Practice Guidelines.
AB  - This study aims to develop and evaluate a mobile application for hypertension
      management based on Clinical Practice Guidelines. The application was developed
      according to Web-Roadmap methodology. In planning phase, we defined the tasks and
      product of each phase, selected clinical practice guidelines and extracted
      intervention items for hypertension management. In analysis phase, we analysed
      intervention items and made data dictionary, rules, use-case diagram,
      hypertension management ontology and tailored recommendations for the
      application. In design phase, we developed an entity-relations diagram,
      algorithm, and user interface and coded them in the implementation phase. In
      evaluation phase, first, the knowledge-base was evaluated for its accuracy by
      experts and they proposed three more detailed recommendations, which were added
      to the application. Second, mobile heuristics were evaluated. The evaluators
      pointed out 33 usability-related problems on mobile heuristics items. Out of
      these, three problems were solved by reflecting evaluators' comments. 

PMID- 25991220
TI  - The impacts of blended learning design in first year medical studies.
AB  - In the first year of medical studies in France, students prepare for a highly
      selective entrance exam limited by numerus clausus into the second year. We have
      discontinued live lectures, made maximum use of new information and communication
      technologies and introduced tutorials in an attempt to make the first year more
      equitable and to personalise teaching. The reform is based on blended learning
      with flipped classroom organized into a four-week cycles of different activities.
      Each cycle corresponds to a learning module. The teachers' and students' opinions
      were analysed to evaluate the reforms and allow teaching methods to be adapted
      accordingly. The student profiles at registration and success in the exams
      following the reform are described. The tutorial's notes are correlated to the
      final scores at the entrance exam. The keys to success seem to be modified by the
      reform providing greater equality of opportunity between students. The factors
      associated to success are baccalaureate highest grades, high School
      Specialisation (maths, physics or earth and life sciences) and repeating the
      first year class. The use of blended learning allows us to face the increase of
      student enrolment, and to facilitate the acceptance of these pedagogical methods
      for both students and teachers. 

PMID- 25991221
TI  - Clinical simulation of aortic valve: a narrative review.
AB  - INTRODUCTION: About 30 percent of the worldwide death is due to cardiovascular
      diseases. Clinical simulation is a promising filed that can help to understand
      diseases, their nature and intervention's effects. The simulated models are
      flexible and make it easy to study the changes' effects and help to select the
      appropriate interventions. This narrative review aims to report common methods
      for the clinical simulation and its merits focusing on the cardiovascular field
      especially those pertaining to the aortic valve. METHOD: The search was conducted
      on google scholar and PubMed in August and September of 2014 with three queries'
      categories. We searched among English papers with no limitation on the published
      year. A qualitative-interpretive approach was used for data extraction. RESULTS:
      Computational fluid dynamic (CFD) is used to simulate and study body structures,
      systems and their common phenomena. Its two common methods for cardiovascular
      simulations are Finite Element Method (FEM) and Finite Volume Method (FVM). There
      were two kinds of the aortic valve simulation: dry models and Fluid-Structure
      Interaction (FSI) models. Unlike the dry model, FSI models consider the
      interaction between blood flow and tissue. Clinical simulation is a promising
      field allowing statistical analysis and can be used in clinical decision support
      systems (CDSS) or as a virtual experimental platform as a training system.

PMID- 25991222
TI  - OpenNCP: a novel framework to foster cross-border e-Health services.
AB  - The continuity of cross-border health care in the European Union depends on the
      ability to set up shared practices with respect to patient data exchange across
      Member States. This flow of data must comply with demanding security, legal and
      interoperability requirements, as defined by the epSOS project specifications. In
      this paper, we describe the OpenNCP framework that offers a comprehensive set of
      interoperability services to enable national and regional e-Health platforms to
      set up cross-border health information networks compliant with epSOS, with
      minimal adaptation of the existing infrastructure. The OpenNCP, available as open
      source software, has been adopted in 10 Member States, allowing them to securely
      interconnect their eHealth infrastructures. 

PMID- 25991223
TI  - GA-ANFIS Expert System Prototype for Prediction of Dermatological Diseases.
AB  - This paper presents novel GA-ANFIS expert system prototype for dermatological
      disease detection by using dermatological features and diagnoses collected in
      real conditions. Nine dermatological features are used as inputs to classifiers
      that are based on Adaptive Neuro-Fuzzy Inference Systems (ANFIS) for the first
      level of fuzzy model optimization. After that, they are used as inputs in Genetic
      Algorithm (GA) for the second level of fuzzy model optimization within GA-ANFIS
      system. GA-ANFIS system performs optimization in two steps. Modelling and
      validation of the novel GA-ANFIS system approach is performed in MATLAB
      environment by using validation set of data. Some conclusions concerning the
      impacts of features on the detection of dermatological diseases were obtained
      through analysis of the GA-ANFIS. We compared GA-ANFIS and ANFIS results. The
      results confirmed that the proposed GA-ANFIS model achieved accuracy rates which
      are higher than the ones we got by ANFIS model. 

PMID- 25991224
TI  - Facilitating the adoption of digital technologies by the elderly.
AB  - This study examined the major criteria needed to facilitate the adoption of a
      technology that aims to support elderly autonomy. A User Centered Design process
      was instigated to design a digital tablet-based application. The two first stages
      consisted of a literature review and two focus groups that aimed respectively: to
      specify interaction principles, and to define the needs and expectations of the
      elderly and collect their feedback on the application's usability. The results
      show that to be accepted the technology has to provide relevant and useful
      information on nearby services, aids and social activities. It also has to
      facilitate the controlled sharing of information and the communication with close
      family/relations, and residential home and external services to both empower the
      elderly and counter loneliness. A summative evaluation will be organised after
      taking into account the current guidelines to further validate the usability of
      the application with elderly people. 

PMID- 25991225
TI  - An integrated Diet Monitoring Solution for nutrigenomic research.
AB  - The emergence of evidence pointing at diet as key risk factor for chronic
      diseases and at gene-diet interactions as key elements in the interplay between
      an individual genetic background and his/her lifestyle, pave the way for studies
      in nutrigenomics. Such studies need an integrated solution to collect, monitor
      and analyse a large set of data. In the frame of ATHENA, a European Commission
      FP7 project, we developed an integrated platform, called Dietary Monitoring
      Solution enabling the collection of phenotypic, genetic and lifestyle
      information, linked to a mHealth application tool. The data collection solution
      allows maintaining anonymized information and supports a number of features
      making it particularly suited for multicentre studies. The mHealth application
      was designed to translate the knowledge generated from research into a
      personalised prevention programme and to support the patient adherence to the
      programme. 

PMID- 25991226
TI  - Draft guideline for the development of evidence based medicine-related apps.
AB  - Evidence based recommendations can significantly aid decision processes in
      medicine and mobile apps are starting to enter this domain. Considering the rapid
      access to and quick processing of information made possible by such apps, it is
      especially important to ensure the quality and structure of the provided data and
      to also keep the limitations of the information sources in mind. A draft
      guideline meant for implementing appropriate standards for such apps is outlined
      in this contribution. 

PMID- 25991227
TI  - User experience integrated life-style cloud-based medical application.
AB  - Having a modern application capable to automatically collect and process data
      from users, based on information and lifestyle answers is one of current
      challenges for researchers and medical science. The purpose of the current study
      is to integrate user experience design (UXD) in a cloud-based medical application
      to improve patient safety, quality of care and organizational efficiency. The
      process consists of collecting traditional and new data from patients and users
      using online questionnaires. A questionnaire dynamically asks questions about the
      user's current diet and lifestyle. After the user will introduce the data, the
      application will formulate a presumptive nutritional plan and will suggest
      different medical recommendations regarding a healthy lifestyle, and calculates a
      risk factor for diseases. This software application, by design and usability will
      be an efficient tool dedicated for fitness, nutrition and health professionals. 

PMID- 25991228
TI  - Designing the user interfaces of a behavior modification intervention for obesity
      & eating disorders prevention.
AB  - The recent immense diffusion of smartphones has significantly upgraded the role
      of mobile user interfaces in interventions that build and/or maintain healthier
      lifestyles. Indeed, high-quality, user-centered smartphone applications are able
      to serve as advanced front-ends to such interventions. These smartphone
      applications, coupled with portable or wearable sensors, are being employed for
      monitoring day to day health-related behaviors, including eating and physical
      activity. Some of them take one step forward by identifying unhealthy behaviors
      and contributing towards their modification. This work presents the design as
      well as the preliminary implementation of the mobile user interface of SPLENDID,
      a novel, sensor-oriented intervention for preventing obesity and eating disorders
      in young populations. This is implemented by means of an Android application,
      which is able to monitor the eating and physical activity behaviors of young
      individuals at risk for obesity and/or eating disorders, subsequently guiding
      them towards the modification of those behaviors that put them at risk. Behavior
      monitoring is based on multiple data provided by a set of communicating sensors
      and self-reported information, while guidance is facilitated through a
      feedback/encouragement provision and goal setting mechanism. 

PMID- 25991229
TI  - Identifying technology interaction opportunities within a gastroenterology exam
      room.
AB  - Gastric cancer is a serious disease that most people usually do not know they
      have until they start to get symptoms. Gastroenterology imaging is an essential
      tool for this battle, since an early diagnosis typically leads to a good
      prognosis. However, this is a rapidly evolving technological area with novel
      imaging devices such as capsule, narrow-band imaging or high-definition
      endoscopy. Adapting to these technologies has a high time-price cost, even for
      experienced clinicians, motivating the appearance of interactive environments
      that can accelerate these training processes. The GEMINI (Gastroenterology Made
      Interactive) project aims to create an interactive clinical decision support
      system (CDSS) that can be used to help with the diagnosis within a
      gastroenterology room during real endoscopic examinations. We used human computer
      interaction (HCI) support methodologies in order to identify interaction
      opportunities. As a final conclusion, the most promising avenue for interactions
      with CDSS is probably using mobile devices such as tablets, controlled by a nurse
      at the physician's request. As future work, we will prototype and evaluate such a
      system in a real hospital environment. 

PMID- 25991230
TI  - Physical activity event regularity and health outcome - 'Undiscovered country' in
      cohort accelerometer data.
AB  - The increasing use of wearable devices for measuring long-term activity data
      allows for detailed analyses of real-life behavioral patterns and for the
      identification of new parameters such as activity event regularity. Thus far, the
      medical relevance of this new regularity parameter is unknown. The objective of
      the research work for this paper is to investigate associations between activity
      regularity and resting systolic blood pressure, as an exemplary well-established
      cardiovascular risk factor. Using accelerometer and blood pressure data of N=5695
      subjects from the NHANES 2005-6 cohort study, three characteristic physical
      activity parameters (regularity, duration and intensity) were computed and
      compared for the upper and lower quartiles of subjects with regard to their blood
      pressure values. Results show statistically significant differences in the
      parameters regularity (p<0.001) and duration (p=0.008) of physical activity
      events, but not in intensity (p=0.889). Results confirm that subjects with low
      resting systolic blood pressure not only are active for longer periods of time,
      but also are more regularly active. It also shows that low-intensity, short-lived
      physical activity (< 10 min.) is associated with health-related outcome
      parameters. More research is necessary to make full use of detailed activity
      behavior data, and in particular to uncover relations between physical activity
      patterns and health outcome. 

PMID- 25991231
TI  - Reshaping the laboratory results presentation layer: three interfaces for
      handheld devices.
AB  - The interpretation of laboratory results is a critical part of the clinical
      decision making process. The proper understanding of many clinical conditions
      depends on the identification of evidences in the laboratory reports. If the
      classic tabular presentation of laboratory results has demonstrated its
      efficiency since many years, the increase number of potential results, the
      increased complexity of cases and the time shortage to analyses cases raise the
      question of finding more efficient ways of displaying these results to
      clinicians. The presentation layer becomes even more crucial when it comes to
      small-sized interactive displays. In this work, we discuss three alternative
      graphical representations of laboratory results adapted to handheld devices. 

PMID- 25991232
TI  - Design and evaluation of a patient website to reduce crowding in emergency
      departments: a preliminary study.
AB  - The study aims to identify the information useful to support a patients' EDs'
      choice in order to design a patient Web-based system. For that purpose, a focus
      group and a formative user test have been performed. The results show that five
      types of information can be relevant. The spontaneous favored information is the
      "distance" to EDs. The "Wait time", that is sanctified in literature, is only
      used in a second time. A larger summative evaluation should be planned to
      evaluate and validate the befits of this kind of tool. 

PMID- 25991233
TI  - Apps for hearing healthcare.
AB  - The hearing healthcare scenario is rapidly evolving due to the pervasive use of m
      Health solutions, in particular mobile apps. This brings along significant
      advantages and opportunities (e.g., accessibility, affordability, personalized
      healthcare, patient empowerment) as well as significant potential risks and
      threats (e.g., safety, misuse, quality issues, privacy). Our research aims at the
      identification and assessment of apps in the hearing healthcare domain. In this
      article we present an overview of the current availability, variety, and
      penetration of hearing-related apps. 

PMID- 25991234
TI  - New technologies applied to surgical processes: Virtual Reality and rapid
      prototyping.
AB  - AYRA is software of virtual reality for training, planning and optimizing
      surgical procedures. AYRA was developed under a research, development and
      innovation project financed by the Andalusian Ministry of Health, called VirSSPA.
      Nowadays AYRA has been successfully used in more than 1160 real cases and after
      proving its efficiency it has been introduced in the clinical practice at the
      Virgen del Rocio University Hospital . Furthermore, AYRA allows generating
      physical 3D biomodels using rapid prototyping technology. They are used for
      surgical planning support, intraoperative reference or defect reconstruction. In
      this paper, some of these tools and some real cases are presented. 

PMID- 25991235
TI  - Experiences as input to eHealth design - a hip surgery patient journey case.
AB  - The objective of the study is to describe the planned hip-surgery care process as
      experienced by patients and healthcare professionals, as well as a qualitative
      analysis of problems. Data was collected through 3 focus group meetings with
      patients and healthcare professionals. We present the results in form of a
      patient journey model, examples of problems as expressed by patients and examples
      of proposed eHealth services by both patients and care professionals. The results
      indicate that although the patient journey is similar for most patients, their
      experiences are highly individual and designing eHealth to improve the patient
      journey will require flexibility and adaptability to the individual's needs. 

PMID- 25991236
TI  - ADVISE: First Results of a European Interoperative Information System Network
      Developed for the ADenoVirus Initiative Study in Epidemiology.
AB  - Adenoviral conjunctivitis is extremely contagious, causes a form of
      conjunctivitis. Therefore, it is important to identify patients who suffer from
      adenoviral conjunctivitis, as early as possible, in order to contain the disease.
      We present the 6 independent but interoperable platforms developed for the
      purpose of a large European epidemiologic study (ADVISE), which has been
      implemented independently in France, Germany, Spain, Italy and the UK. ADVISE is
      a non-interventional, observational epidemiology study with the objectives of
      assessing clinical characteristics and incidence of adenovirus conjunctivitis.
      One of the challenges faced in developing this network of European epidemiology
      platforms has been the multilingual context. Actually, we have established
      independent platforms fully dedicated to each of the participating countries.
      Similar protocols have been submitted across these countries, allowing individual
      and pooled analyses of the data. A standardized questionnaire is used to collect
      patient ocular medical history. The electronic questionnaire contains 151 items
      with automatic coherence control. The first platform ADVISE was set up in France.
      Development, evaluation and validation of this platform were carried out between
      January and July 2013. The Medical Informatics and Knowledge Engineering
      Laboratory (LIMICS), proposes through this project, a tool that allows the
      installation and application of epidemiologic monitoring in any part of the
      world. 

PMID- 25991237
TI  - iCarer: AAL for the Informal Carers of the Elderly.
AB  - In the context of the long-term care for older adults, informal carers play a key
      role. Daily competing priorities or a care-skills deficit may lead them to
      stress, anxiety and/or depression. The iCarer project (AAL-2012-5-239) proposes
      the design and implementation of a cloud-inspired personalised and adaptive
      platform which will offer support to informal carers of older adults with
      cognitive impairment. By means of a holistic approach comprising technologies and
      services addressing the intelligent and interactive monitoring of activities,
      knowledge management for personalised guidance and orientation, virtual
      interaction, e-learning, care coordination facilities and social network
      services, iCarer aims to reduce the informal carer stress and to enhance the
      quality of care they provide, thus improving their quality of life. The iCarer
      platform will be evaluated through a multi-centre non-controlled study (4 months;
      48 homes located in England and in Slovenia). Currently the iCarer project is
      completing the development work. The evaluation trial is expected to start in
      August 2015. 

PMID- 25991238
TI  - A Medical Application to Bridge the Gap between Clinicians and Clinical Data.
AB  - There currently exists a gap between medical data and the clinicians who wish to
      use the data as the foundation for evidence-based medicine. The current
      disjointed workflow often requires statisticians to act as bridges in order to
      answer inquiries from clinicians. This can lead to suboptimal results as due to a
      gap between the fundamental understanding of clinical underpinnings and formal
      statistical interpretation of the data. To address this challenge, we have
      created a multi-platform application that allows clinicians to quickly and easily
      navigate and analyse the data. This application has been successfully implemented
      and tested within the Urology department at Mount Sinai Hospital for
      comprehensive analysis of complex urological data. 

PMID- 25991240
TI  - Virtual file system on NoSQL for processing high volumes of HL7 messages.
AB  - The Standardized Structured Medical Information Exchange (SS-MIX) is intended to
      be the standard repository for HL7 messages that depend on a local file system.
      However, its scalability is limited. We implemented a virtual file system using
      NoSQL to incorporate modern computing technology into SS-MIX and allow the system
      to integrate local patient IDs from different healthcare systems into a universal
      system. We discuss its implementation using the database MongoDB and describe its
      performance in a case study. 

PMID- 25991241
TI  - Analysis of care pathway variation patterns in patient records.
AB  - A care/clinical pathway (CP) is a standardized care process where temporal and
      data constraints of clinical activities are defined to ensure quality of care. In
      actual care practice, various situations of compliance and non-compliance with
      CPs can be observed. Analysis of these CP variation patterns (CPVPs) can help
      improve care quality and enhance decision support. In this paper, we propose an
      automatic method to detect CPVPs in electronic medical records (EMR), and
      statistically examine their correlation with patient outcomes. From each CP
      constraint, we first derive a CPVP tree, where each pattern is represented using
      first-order linear temporal logic and translated into a Buchi automaton for
      pattern detection. Then we identify the CPVPs that are evidently correlated with
      a patient outcome by examining the odds ratios. The method has been applied to a
      CP for congestive heart failure and real world EMR to demonstrate the
      effectiveness. 

PMID- 25991242
TI  - A Big Data-driven Model for the Optimization of Healthcare Processes.
AB  - Healthcare organizations increasingly navigate a highly volatile, complex
      environment in which technological advancements and new healthcare delivery
      business models are the only constants. In their effort to out-perform in this
      environment, healthcare organizations need to be agile enough in order to become
      responsive to these increasingly changing conditions. To act with agility,
      healthcare organizations need to discover new ways to optimize their operations.
      To this end, they focus on healthcare processes that guide healthcare delivery
      and on the technologies that support them. Business process management (BPM) and
      Service-Oriented Architecture (SOA) can provide a flexible, dynamic, cloud-ready
      infrastructure where business process analytics can be utilized to extract useful
      insights from mountains of raw data, and make them work in ways beyond the
      abilities of human brains, or IT systems from just a year ago. This paper
      presents a framework which provides healthcare professionals gain better insight
      within and across your business processes. In particular, it performs real-time
      analysis on process-related data in order reveal areas of potential process
      improvement. 

PMID- 25991243
TI  - Semantic integration of medication data into the EHOP Clinical Data Warehouse.
AB  - Reusing medication data is crucial for many medical research domains. Semantic
      integration of such data in clinical data warehouse (CDW) is quite challenging.
      Our objective was to develop a reliable and scalable method for integrating
      prescription data into EHOP (a French CDW). METHOD: PN13/PHAST was used as the
      semantic interoperability standard during the ETL process, and to store the
      prescriptions as documents in the CDW. Theriaque was used as a drug knowledge
      database (DKDB), to annotate the prescription dataset with the finest
      granularity, and to provide semantic capabilities to the EHOP query workbench.
      RESULTS: the system was evaluated on a clinical data set. Depending on the use
      case, the precision ranged from 52% to 100%, Recall was always 100%. CONCLUSION:
      interoperability standards and DKDB, document approach, and the finest
      granularity approach are the key factors for successful drug data integration in
      CDW.

PMID- 25991244
TI  - Integrating medical and research information: a big data approach.
AB  - Most of the information collected in different fields by Instituto de
      Investigacion Biomedica de A Coruna (INIBIC) is classified as unstructured due to
      its high volume and heterogeneity. This situation, linked to the recent
      requirement of integrating it to the medical information, makes it necessary to
      implant specific architectures to collect and organize it before it can be
      analysed. The purpose of this article is to present the Hadoop framework as a
      solution to the problem of integrating research information in the Business
      Intelligence field. This framework can collect, explore, process and structure
      the aforementioned information, which allow us to develop an equivalent function
      to a data mart in an Intelligence Business system. 

PMID- 25991245
TI  - Measuring Data Quality: A Review of the Literature between 2005 and 2013.
AB  - A literature review was done within a revision of a guideline concerned with data
      quality management in registries and cohort studies. The review focused on
      quality indicators, feedback, and source data verification. Thirty-nine relevant
      articles were selected in a stepwise selection process. The majority of the
      papers dealt with indicators. The papers presented concepts or data analyses. The
      leading indicators were related to case or data completeness, correctness, and
      accuracy. In the future, data pools as well as research reports from quantitative
      studies should be obligatory supplemented by information about their data
      quality, ideally picking up some indicators presented in this review. 

PMID- 25991247
TI  - Ethical, Legal and Social Issues related to the health data-warehouses: re-using
      health data in the research and public health research.
AB  - Research derived from the application of information and communication
      technologies in medicine operates in a context involving the globalization of
      collecting, sharing, storage, transfer and re-use of personal health data. Health
      data computerization within Clinical Information Systems (as Electronic
      Healthcare Records) should allow the re-use of health data for clinical research
      and public health purposes. One of the objects allowing the integration of
      healthcare and research information systems is the health data-warehouse (DWH).
      However, ethical-legal frameworks in force are not adapted to these DWHs because
      they were not conceived for re-using data in a different context than the one of
      their acquisition. For that matter, access modalities to data-warehouses must
      ensure the respect of patients' rights: information to the patient, as well as
      confidentiality and security. Through a bibliography research, some Ethical,
      legal and Social Issues (ELSI) have been identified: Patients' rights Modalities
      of implementation of the DWs; Solidarity and common good; Transparency and Trust.
      Comparative analysis between the Directive 95/46/CE and the "Proposal for
      regulation on protection of individuals with regard to the processing of personal
      data" shows that this regulation pretends allowing the re-use of key-coded data
      when aimed at a scientific purpose. However, since this new regulation does not
      align with the ethical and legal requirements at an operational level, a Code of
      practice on secondary use of Medical Data in scientific Research Projects has
      been developed at the European Level. This Code provides guidance for Innovative
      Medicine Initiative (IMI) and will help to propose practical solutions to
      overcome the issue of the re-use of data for research purposes. 

PMID- 25991248
TI  - How to represent the decision process in a medication plan: the case of the Swiss
      cohort of inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) belong to healthcare problems impacting the
      quality of life and inducing important costs for the healthcare system. There is
      still no magical cure against this kind of diseases, but many promising therapies
      are under investigation. In order to study the efficiency and side effects of the
      existing drugs and to evaluate new ones, large numbers of patients are followed
      in long term cohort studies. The particular constraints associated to the follow
      up of patients with IBD require the implementation of adapted and efficient
      tools. On the one hand, clinicians must be able to perform daily changes to the
      patient treatment in order to adapt it for its best efficiency and react to side
      effects. On the other hand, the tool must provide long term view on the data to
      allow large scale analyses regarding the efficiency of the investigated
      treatment. There are few solutions allowing a clear visualization of the
      treatment plan of the patients in the long term that indicates clearly the
      changes and the adverse events. In this work, we propose a new integrated tool
      that offers a clear temporal view over the patients' treatment. 

PMID- 25991249
TI  - A high-availability architecture for continuous monitoring of sleep disorders.
AB  - We present a complete technical solution for continuously monitoring vital signs
      required for observing sleep apnoea events, one of the major sleep respiratory
      disorders. Based on industry accepted medical devices, we developed a GSM-based
      remote data acquisition and transfer module that is integrated via a set of web
      services into the server side of the application. The back-end is responsible
      with aggregating all the data, and, based on machine learning techniques, it
      provides a first level of filtering in order to warn about possible
      abnormalities. The proposed solution is currently under the test phase at the
      "Victor Babes" Hospital in Timisoara, Romania. 

PMID- 25991250
TI  - Sharing models and tools for processing German clinical texts.
AB  - The automatic processing of non-English clinical documents is massively hampered
      by the lack of publicly available medical language resources for training,
      testing and evaluating NLP components. We suggest sharing statistical models
      derived from access-protected clinical documents as a reasonable substitute and
      provide solutions for sentence splitting, tokenization and POS tagging of German
      clinical texts. These three components were trained on the confidential FRAMED
      corpus, a non-sharable collection of various German-language clinical document
      types. The models derived therefrom outperform alternative components from
      OPENNLP and the Stanford POS tagger, also trained on FRAMED. 

PMID- 25991251
TI  - Detecting Learning and Reasoning Patterns in a CDSS for Dementia Investigation.
AB  - Reasoning conducted in clinical practice is manifested through different and
      often combined reasoning and learning strategies, adjusted to the characteristics
      of the available information, the medical professional's experience and skills,
      and the available tools, such as clinical practice guidelines. This research
      outlines a design model for supporting the commonly used strategies. This design
      model was implemented into a clinical decision-support system (CDSS), in addition
      to a method for detecting reasoning strategies applied when using the CDSS. This
      method was applied in a case study, with preliminary results presented in this
      paper and will be further implemented in future studies. 

PMID- 25991252
TI  - A new tool for foetal phonocardiography simulation.
AB  - Among diagnostic techniques for foetal monitoring, phonocardiography is gaining
      more and more interest for its low cost, passive nature and capability to detect
      some cardiac diseases. In spite of these characteristics, its use in clinical
      routine is still limited due to different troubles; for example, signals recorded
      through maternal abdomen show generally a quite low signal-to-noise ratio, so
      that detection and analysis of foetal heart sounds result very difficult. In this
      scenario, the availability of artificial phonocardiographic signals, simulated
      with conditions resembling different foetal conditions, week of gestation and
      noise amount, to name someone, can be a very useful tool to train medical staff.
      In this paper a software for phonocardiography simulation, updated to take
      account also of the split is presented. The software is completed with a user
      interface which allow to modify in a simple way simulation parameters. It is
      worth highlighting that this software can be useful also for testing performances
      of other analysis software and mathematical tools for recognising of valves
      components in the heart sounds. 

PMID- 25991254
TI  - ISO 13606 based system for biomedical parameter storage, querying and alarm
      detection.
AB  - ACHEGAMED is an unsupervised real-time patient monitoring system, with the goal
      of decreasing the exam and diagnosis time of the most prevalent diseases in
      today's healthcare services. We developed, as a component of ACHEGAMED, a system
      for storing a wide range of biomedical parameters as ISO 13606 extracts. The
      system is able to detect clinical alarms in those parameters and communicate
      them, if needed, to the appropriate medical staff. Although a component of
      ACHEGAMED, it can be integrated in other systems in a semantic interoperable way
      thanks to the ISO 13606 standard, allowing the continuity of patient care. 

PMID- 25991255
TI  - A CAD System for the Acquisition and Classification of Breast TMA in Pathology.
AB  - Breast cancer is the most common type of cancer and the fifth leading cause of
      death in women over 40. Therefore, prompt diagnostic and treatment is essential.
      In this work a TMA Computer Aided Diagnosis (CAD) system has been implemented to
      provide support to pathologists in their daily work. For that purpose, the tool
      covers each and every process from the TMA core image acquisition to their
      individual classification. The first process includes: tissue core location,
      segmentation and rigid registration of digital microscopic images acquired at
      different magnifications (5x, 10x, 20x, 20x and 40x) from different devices. The
      classification process allows performing the core classification selecting
      different types of color models, texture descriptors and classifiers. Finally,
      the cores are classified into three categories: malignant, doubtful and benign. 

PMID- 25991256
TI  - Computational study of the self-assembly of two different cell populations in
      contact with a biomaterial.
AB  - The organisation of a heterotypic multicellular system is intensely studied in
      developmental biology, tissue engineering and regenerative medicine.To address
      this problem, we have created a computational model of a biological system made
      of two cell populations of various cohesivities, and simulated its evolution on
      the surface of biomaterials of different adhesivities. To this end, it was
      necessary to extend our SIMMMC application with algorithms that treat two cell
      types. We have observed, in accordance with experiments that, depending on the
      strength of cell-substrate adhesion, different structures emerge by the self
      assembly of the two cell populations. The agreement with experimental results
      validates the extended version of the SIMMMC application, suggesting that this
      tool might offer useful insights for tissue engineers. 

PMID- 25991257
TI  - Privacy-preserving Statistical Query and Processing on Distributed OpenEHR Data.
AB  - Reuse of data from EHRs is essential for many purposes. The objective of the
      study was to explore how distributed electronic health record (EHR) data can be
      reused for privacy-preserving statistical query and processing. METHOD: We have
      designed and created a proof of concept prototype solution based on the OpenEHR
      specification to ensure interoperability and to query the EHRs. XMPP was used for
      communication between the distributed processing components. RESULTS: We have
      created a two-phased process where a distributed virtual dataset is first created
      and thereafter processed using distributed privacy-preserving statistical
      queries. CONCLUSION: Health authorities in Norway are currently defining the set
      of archetypes for the national interoperability program. This will create a
      common information schema enabling reuse of EHR data for statistical query and
      processing in a privacy-preserving manner. One benefit of the approach is that
      information transformation between information models for clinical use and
      statistical processing can be avoided.

PMID- 25991258
TI  - A method to pinpoint undiscovered links in genetic and protein networks.
AB  - Due to the still largely undiscovered gene interactions working with incomplete
      data is necessary. This paper presents a method to determine the information gap
      required to create a complete and workable depiction of a specific interaction
      network, starting from a database. 

PMID- 25991259
TI  - A socio-technical analytical framework on the EHR-organizational innovation
      interplay: Insights from a public hospital in Greece.
AB  - The healthcare sector globally is confronted with increasing internal and
      external pressures that urge for a radical reform of health systems' status quo.
      The role of technological innovations such as Electronic Health Records (EHR) is
      recognized as instrumental in this transition process as it is expected to
      accelerate organizational innovations. This is why the widespread uptake of EHR
      systems is a top priority in the global healthcare agenda. The successful co
      deployment though of EHR systems and organizational innovations within the
      context of secondary healthcare institutions is a complex and multifaceted issue.
      Existing research in the field has made little progress thus emphasizing the need
      for further research contribution that will incorporate a holistic perspective.
      This paper presents insights about the EHR-organizational innovation interplay
      from a public hospital in Greece into a socio-technical analytical framework
      providing a multilevel set of action points for the eHealth roadmap with
      worldwide relevance. 

PMID- 25991261
TI  - A framework for evaluating mHealth tools for Older Patients on Usability.
AB  - Mobile health (mHealth) apps can play a significant role in supporting older
      patients. The aging process is yet related to progressive degradation of sensory,
      physical and cognitive abilities. mHealth apps with touch screen based interfaces
      thus need to be adapted to the, often impaired, skills and special needs of older
      patients. However, existing design guidelines for mHealth apps do not address the
      aging barriers that older users face in working with touch screen based
      applications. By means of a constructed conceptual framework on cognitive,
      motivational, physical and visual impairments of older adults, this study
      revealed possible aging barriers concerning identified usability issues of an
      mHealth app for older patients. Insights into the aging process barriers that
      underlie usability issues supports developers in (re)designing mHealth apps that
      are better attuned to the needs of the older patient population. 

PMID- 25991262
TI  - A mobile application supporting outpatient treatment and follow-up.
AB  - An increasing prevalence of chronic diseases is observed, among which cancer is
      now included because of its survival rates. That trend requires new ways of
      supporting outpatients and improving their compliance to treatments. This paper
      introduces HeNeA, a mobile application designed to support patients affected by
      Head and Neck cancer during their treatments. The application leverages on the
      mHealth features described in the literature and has been reviewed by a small set
      of patients during its development. Further evaluation is expected to occur when
      it will be offered to every eligible patient discharged from the Head and Neck
      division of a major Italian cancer centre. 

PMID- 25991263
TI  - Mobile health apps in Sweden: what do physicians recommend?
AB  - BACKGROUND: Currently over 50,000 mobile health apps are available worldwide. In
      general, they are considered as innovations potentially delivering benefits to
      patients. Physicians are considered as potential channels to disseminate these
      innovations to patients. However, physicians' behavior in this regard has not
      been studied. OBJECTIVES: To capture physicians' attitudes towards recommending
      health apps to patients and to describe factors influencing physicians' behavior,
      taking the specifics of an early adopter country, Sweden, into account. METHODS:
      Diffusion of Innovation theory, the Health App Maturity Model and the Six Hurdles
      Model were used to construct a web-based survey that was answered by 44 Swedish
      physicians. Survey results were followed up with 2 individual interviews.
      Descriptive statistics were used for quantitative data analysis and recursive
      abstraction for qualitative data analysis. RESULTS: Only a small group of
      physicians currently recommend mobile health apps to their patients. However,
      most physicians have a positive attitude and perceive improvement of patients'
      self-management ability as main benefit of health apps. Main perceived weaknesses
      include the lack of evidence-based content and lack of multi-language support.
      Regulation of health apps under the Medical Device Directive is asked for to
      assure quality and patient safety. CONCLUSION: Innovators and early adopters play
      an important role in the diffusion of mobile health apps. Interpersonal
      communication is seen as the most effective way for physicians gaining
      information and also motivates them to recommend mobile health apps to their
      patients. Physicians' knowledge about certified websites to ensure quality is
      however low.

PMID- 25991264
TI  - A mobile application to manage and minimise the risk of late effects caused by
      childhood cancer.
AB  - In their first 15 years of life, about 1 800 children are diagnosed with cancer
      each year in Germany. Their chances of survival, however, have improved
      significantly over the last 40 years. In Germany alone, over 30 000 survivors of
      childhood cancer are presently living. Therefore, the late effects caused by the
      therapy occur ever more frequently as chemotherapy and radiotherapy may leave
      traces even years later. In order to recognize and treat these late effects in
      survivors, structured and regular follow-up examinations are necessary from an
      early stage on. However, the compliance of former patients to participate in the
      recommended check-ups is not satisfying for multiple reasons. To enhance this
      compliance, an application for smartphones and tablets has been developed. The
      Aftercare App supplies a wide range of information regarding the aftercare and
      supports a reminder functionality to attend medical visits. 

PMID- 25991265
TI  - Nurses behaviour pre and post the implementation of data capture using tablet
      computers in a rural clinic in South Africa.
AB  - This Time and Motion study was part of a larger Open Source Development Project
      to evaluate the use of Tablet computers for collecting patient data in rural
      clinics in the OR Tambo District, Eastern Cape, South Africa. The intention was
      to determine if there were any differences in the activities and workloads
      between the two methods of data capture. The main difference between the Phases
      was that the number of activities undertaken per patient decreased in the second
      phase. More time was spent on each activity. 

PMID- 25991266
TI  - How to organize for a large-scale openEHR-based Electronic Patient Record.
AB  - This paper reports from a large-scale openEHR-based EPR project 2012-2016 in the
      North Norway Regional Health Authority. To be able to support patient pathways
      across the health region's trusts, there is a need for standardized routines and
      practices. Therefore, the North Norway Regional Health Authority has since 2011
      had an increased regional focus to prepare for this new system. This includes a)
      centralizing its IT portfolio to one location, b) creating regional work
      standards for using the EPR system, and c) establishing a Regional Department for
      functional ICT. There are several challenges connected to changing the focus from
      working as individual health trusts to work as one region. There are issues of
      power balance and local influence that will need a careful consideration to
      ensure a successful outcome. 

PMID- 25991267
TI  - The Impact of eHealth and mHealth on doctor behavior and patient involvement: an
      Israeli and Portuguese comparative approach.
AB  - Based on the experience of a Short Term Scientific Mission (STSM) promoted by
      COST Net and developed in CIES/ISCTE-IUL (Portugal), this paper presents a
      reflection about the implementation of Information & Communication Technologies
      (ICT) in the healthcare sector in Israel and Portugal. Specifically, we focus on
      the impacts of ICT or eHealth on patient empowerment, as perceived by doctors and
      managers in order to better comprehend the role of national policy and explore
      the options for building a national strategy regarding ICT in healthcare. The
      experience of the Portuguese healthcare system was selected and compared to the
      results found in a similar research in Israel. Methodologically, in-depth
      interviews with the Ministry of Health, the private sector, patients associations
      and researches were used to collect data. Purposeful sampling was used to select
      respondents, and secondary sources were used for triangulation. The findings of
      the research work show that the increased deployment of ICT has furthered patient
      empowerment (1). From the doctors' perspective, while ICT has provided more
      information in the long-run, changes of these magnitudes were not easy in the
      beginning. These findings were similar in both countries. The work concludes that
      ICT tools were successfully implemented and the general perception is that they
      have been beneficial. The work provides information in order to understand and
      improve ICT services. Additionally, the results suggest alternatives for future
      investments in these technologies. 

PMID- 25991268
TI  - A mobile platform for emergency care.
AB  - The paper describes the adaptation of a mobile platform initially developed for
      designing and administering questionnaires to a new context supporting checklists
      in emergency care. We took part in the checklists formalization process together
      with the domain experts and recognized that some tasks would highly benefit from
      the inherent features offered by the mobile technology. Thus we exploited the
      robustness of the model already designed for navigating among questionnaires and
      implemented additional functionalities that improved the usability of the mobile
      application, making it suitable for the paramedic staff and the volunteers that
      manage emergency cases. 

PMID- 25991269
TI  - Privacy provision in eHealth using external services.
AB  - Privacy provision is a key issue for successful secure access to patients' health
      information. Current approaches do not always provide patients with the ability
      to define suitable rules to access to their information in a secure way. This
      paper presents an approach to give patients control over their information by
      means of external services. In this way, health information management and access
      control are kept independent and more secure. 

PMID- 25991270
TI  - Heart rate prediction for coronary artery disease patients (CAD): Results of a
      clinical pilot study.
AB  - This paper describes the results of a pilot study with cardiac patients based on
      information that can be derived from a smartphone. The idea behind the study is
      to design a model for estimating the heart rate of a patient before an outdoor
      walking session for track planning, as well as using the model for guidance
      during an outdoor session. The model allows estimation of the heart rate several
      minutes in advance to guide the patient and avoid overstrain before its
      occurrence. This paper describes the first results of the clinical pilot study
      with cardiac patients taking beta-blockers. 9 patients have been tested on a
      treadmill and during three outdoor sessions each. The results have been derived
      and three levels of improvement have been tested by cross validation. The overall
      result is an average Median Absolute Deviation (MAD) of 4.26 BPM between measured
      heart rate and smartphone sensor based model estimation. 

PMID- 25991272
TI  - How much does hyperkalemia lengthen inpatient stays? About methodological issues
      in analyzing time-dependant events.
AB  - Adverse events may increase the hospital length of stay (LOS). As a consequence,
      computing the mean difference of LOS between two inpatient groups, with or
      without event, is a convenient way to evaluate their severity. Conversely, some
      adverse events are time-dependent: this leads to overestimate the consequences of
      the adverse event when statistical tests are performed. In this paper, we
      interest on hyperkalemia in the inpatient database of a community hospital (2% of
      the inpatient stays). The cumulated risk of hyperkalemia appears to be a linear
      function of the LOS. We compute the LOS difference associated with hyperkalemia
      by using 17 statistical methods. The raw LOS difference is 8.8 days, but the
      simulation finds a difference of 2.3 days, while the regressions (with linear or
      log link, with or without pairing, with or without propensity score) find a
      difference of 4.4 to 4.6 days. The characteristics of the methods are discussed,
      but it is not possible to know which one is true. However the raw difference
      seems to overestimate the truth. This methodological bias is quite frequent and
      is a challenge in public health, as it participates in false knowledge discovery,
      which could lead decision makers to focus on wrong issues and make wrong
      decisions. 

PMID- 25991273
TI  - A health analytics semantic ETL service for obesity surveillance.
AB  - The increasingly large amount of data produced in healthcare (e.g. collected
      through health information systems such as electronic medical records - EMRs or
      collected through novel data sources such as personal health records - PHRs,
      social media, web resources) enable the creation of detailed records about
      people's health, sentiments and activities (e.g. physical activity, diet, sleep
      quality) that can be used in the public health area among others. However,
      despite the transformative potential of big data in public health surveillance
      there are several challenges in integrating big data. In this paper, the
      interoperability challenge is tackled and a semantic Extract Transform Load (ETL)
      service is proposed that seeks to semantically annotate big data to result into
      valuable data for analysis. This service is considered as part of a health
      analytics engine on the cloud that interacts with existing healthcare information
      exchange networks, like the Integrating the Healthcare Enterprise (IHE), PHRs,
      sensors, mobile applications, and other web resources to retrieve patient health,
      behavioral and daily activity data. The semantic ETL service aims at semantically
      integrating big data for use by analytic mechanisms. An illustrative
      implementation of the service on big data which is potentially relevant to human
      obesity, enables using appropriate analytic techniques (e.g. machine learning,
      text mining) that are expected to assist in identifying patterns and contributing
      factors (e.g. genetic background, social, environmental) for this social
      phenomenon and, hence, drive health policy changes and promote healthy behaviors
      where residents live, work, learn, shop and play. 

PMID- 25991274
TI  - Usability Evaluation of a COPD Remote Monitoring Application.
AB  - Telemedicine applications have the potential to enhance patient's safety at home
      by remote monitoring of chronic diseases. Telemedicine involves the interaction
      between multiple user groups through a system, making the usability aspect of
      such system crucial for the continuous, efficient and satisfactory use of the
      application. The main objective of this study was to carry out a usability
      evaluation in the field of a telemedicine application for remote monitoring of
      chronic obstructive pulmonary disease (COPD) patients to improve the
      application's user interface before system deployment. A field trial was
      performed with six COPD patients at their homes, continuously using the system's
      application on a tablet for seven days. The usability evaluation identified 23
      usability problems related to users' interactions and system's functionality.
      These problems were solved with the refinement of the system through an iterative
      application development process. The outcome of the study was the improved
      telemedicine application that was adopted by the partners of the FP7 EU project
      United4Health. 

PMID- 25991275
TI  - Applying machine learning to gait analysis data for disease identification.
AB  - A machine-learning framework to identify the specific disease afflicting certain
      patients diagnosed with Neurological and Neuromuscular Diseases (NND) or Juvenile
      Idiopathic Arthritis (JIA) using only gait analysis data is presented.
      Classifying such data into disease types consumes valuable clinical time that may
      be better spent. Effective classification also facilitates its future retrieval.
      To prove the feasibility of the approach, we applied it to the simpler case of
      identifying the disease class of patients with a view to extending the method to
      specific diseases in future work. Standard clinical gait information of healthy
      individuals, and NND/JIA patients was sourced from hospitals participating in MD
      PAEDIGREE. To classify the data into one of the three categories: healthy, NND,
      and JIA, certain parameters were carefully selected from the signals and used to
      train Random Forest (RF), boosting, Multilayer Perceptron (MLP), and Support
      Vector Machine (SVM) classifiers. Cross-validation was used to test the
      effectiveness of our approach and it yields a classification accuracy of 100% for
      RF, SVM, and MLP classifiers and 96.4% for boosting. Training and testing for all
      the classifiers took mere milliseconds, providing opportunities for real-time
      applications. To extend the method to the identification of specific illnesses,
      more discerning features from the gait data are currently being investigated.
      Moreover, a larger dataset is being gathered. Finally, we are attempting to
      reduce the number of features used for classification in order to further
      decrease computation time and algorithm complexity. 

PMID- 25991276
TI  - Public Health Triangulation to inform decision-making in Belgium.
AB  - We assessed the impact of a nation-wide ambulatory care complex intervention (the
      "care trajectory program") on quality of care in Belgium. We used the three-step
      public health triangulation method described in this paper and data from four
      different data sources: a national reimbursement database, an electronic patient
      record-based general practitioner network, the Belgian general practitioner
      sentinel network, and a new national registry for care trajectory patients. By
      applying our method and using the available evidence, we identified key findings
      that have been accepted by experts and stakeholders. We also produced timely
      recommendations for the decision-making process, four years after the start of
      the care trajectory program. 

PMID- 25991277
TI  - An original imputation technique of missing data for assessing exposure of
      newborns to perchlorate in drinking water.
AB  - INTRODUCTION: Incompleteness of epidemiological databases is a major drawback
      when it comes to analyzing data. We conceived an epidemiological study to assess
      the association between newborn thyroid function and the exposure to perchlorates
      found in the tap water of the mother's home. Only 9% of newborn's exposure to
      perchlorate was known. The aim of our study was to design, test and evaluate an
      original method for imputing perchlorate exposure of newborns based on their
      maternity of birth. METHODS: In a first database, an exhaustive collection of
      newborn's thyroid function measured during a systematic neonatal screening was
      collected. In this database the municipality of residence of the newborn's mother
      was only available for 2012. Between 2004 and 2011, the closest data available
      was the municipality of the maternity of birth. Exposure was assessed using a
      second database which contained the perchlorate levels for each municipality. We
      computed the catchment area of every maternity ward based on the French
      nationwide exhaustive database of inpatient stay. Municipality, and consequently
      perchlorate exposure, was imputed by a weighted draw in the catchment area.
      Missing values for remaining covariates were imputed by chained equation. A
      linear mixture model was computed on each imputed dataset. We compared odds
      ratios (ORs) and 95% confidence intervals (95% CI) estimated on real versus
      imputed 2012 data. The same model was then carried out for the whole imputed
      database. RESULTS: The ORs estimated on 36,695 observations by our multiple
      imputation method are comparable to the real 2012 data. On the 394,979
      observations of the whole database, the ORs remain stable but the 95% CI tighten
      considerably. DISCUSSION: The model estimates computed on imputed data are
      similar to those calculated on real data. The main advantage of multiple
      imputation is to provide unbiased estimate of the ORs while maintaining their
      variances. Thus, our method will be used to increase the statistical power of
      future studies by including all 394,979 newborns.

PMID- 25991279
TI  - Process assessment by automated computation of healthcare quality indicators in
      hospital electronic health records: a systematic review of indicators.
AB  - The objective of the work is to extract healthcare process quality indicators
      from the literature, and to evaluate which of them could be automatically
      computed using routinely collected data from electronic health records (EHRs). A
      minimal set of data commonly available in EHRs is first defined. The initial
      bibliographic query enables to identify 8,744 papers, among which 126 papers
      describe 440 process indicators. 22.3% of indicators can be automatically
      computed. The computation of the indicators mostly require diagnoses (99%), drug
      prescriptions (59%), medical procedures (48%), administrative data (30%),
      laboratory results (20%), free-text reports with basic keyword research (19%),
      linkage with the patient's previous stays (11%) and dependence assessment (3%).
      77.7% of indicators cannot be automatically computed, mostly because they require
      a linkage with outpatient data (61%), structured data that are usually not
      available (43%), unstructured data (26%) or the trace of an information that was
      given to the patient (8%). 

PMID- 25991280
TI  - EHR System MojTermin: Implementation and Initial Data Analysis.
AB  - Healthcare informatics has gained importance over the last several years. E
      health systems on a national level have already been implemented in most European
      countries. Data generated by these systems are used to improve healthcare
      policies as well as health services. In this paper we present the system
      MojTermin (MyAppointment), as it evolves from a healthcare appointment engine to
      a complete national e-health system. We also present preliminary results from
      data gathered during the implementation of this system. In our analysis, we show
      how the system aided in the discovery of several specific socio-cultural
      phenomena, which led to governance changes in order to optimize resourses and
      raise the quality of the entire national healthcare system. 

PMID- 25991281
TI  - Development of ISO 13606 archetypes for the standardisation of data registration
      in the Primary Care environment.
AB  - On daily procedures, companies and organizations produce a wide quantity of data.
      Medical information doubles every five years approximately, and most of this
      information has no structure and cannot be utilised. Information obtained during
      Primary Health Care (PC) consultations is expected to be standardized and
      organised following instructions made by archetype 13606 of the International
      Organization for Standardization (ISO) in order to guarantee the Continuity of
      Care as well as the potential use of these data for secondary purposes, such as
      investigation or statistics. This study was designed to investigate the
      feasibility of representing the information collected in Primary Care
      consultations in a structured and normalized way. A key difference to other
      approaches is that the intended solution is, to the best of our knowledge, the
      first one to register all the information collected in this area. The
      participation of the Primary Health Care service (PC) from Complejo Hospitalario
      Universitario de A Coruna (CHUAC) has been of vital importance in this project as
      it has provided the necessary clinical knowledge and it has allowed us to verify
      the effectiveness obtained in actual environments. The archetypes developed can
      be reused in a wide range of projects. As an example of use, we have used these
      archetypes to create an intelligent system that generates organised reports based
      on the information dictated on a medical consultation which, afterwards, can be
      analysed from an analytical point of view. 

PMID- 25991282
TI  - Implementation of a Cloud-based Blood Pressure Data Management System.
AB  - Regular monitoring of blood pressure of a patient can improve hypertension
      diagnosis and treatment. The objective of this study is to design and implement a
      cloud computing based blood pressure data management system that allows patients,
      nurses, physicians, and researchers to access data through the Internet anytime,
      anywhere and via any device. 

PMID- 25991283
TI  - A "pivot" Model to set up Large Scale Rare Diseases Information Systems:
      Application to the Fibromuscular Dysplasia Registry.
AB  - The SIR-FMD project is a partnership between the Department of Genetics and
      Reference Centre for Rare Vascular Diseases at the Georges Pompidou European
      Hospital in Paris and the Medical Informatics and Knowledge Engineering
      Laboratory of Inserm. Its aim is to use an ontological approach to implement an
      information system for the French Fibromuscular Dysplasia Registry. The existing
      data was dispersed in numerous databases, which had been created independently.
      These databases have different structures and contain data of diverse quality.
      The project aims to provide generic solutions for the management of the
      communication of medical data. The secondary objective is to demonstrate the
      applicability of these generic solutions in the field of rare diseases (RD) in an
      operational context. The construction of the French FMD registry was a multistep
      process. A secure platform has been available since the beginning of November
      2013. The medical records of 471 patients from the initial dataset provided by
      the HEGP-Paris, France have been included, and are accessible from a secure user
      account. Users are organized into a collaborative group, and can access patient
      groups. Each electronic patient record contains more than 2,200 items. The
      problem of semantic interoperability has become one of the major challenges for
      the development of applications requiring the sharing and reuse of data. The
      information system component of the SIR-FMD project has a direct impact on the
      standardisation of coding of rare diseases and thereby contributes to the
      development of e-Health. 

PMID- 25991284
TI  - Serious game scores as health condition indicator for cancer patients.
AB  - In this paper we present INTERACCT (Integrating Entertainment and Reaction
      Assessment into Child Cancer Therapy), a multidisciplinary research project
      aiming at creating a communication tool for pediatric patients after cancer
      treatment with HSCT (hematopoietic stem cell transplantation) in after care. The
      communication platform should foster communication between patients and
      clinicians, but also increase motivation for treatment compliance by using
      appropriate designs and gamification elements. A state of the art web interface
      enables the physicians to evaluate data submitted by the patients, joining data
      from various sources (lab data, survey data, physiotherapy performance) using HL7
      and visualizing imporant changes. This contribution outlines the challenges of
      designing such a system and presents a solution for the medical data interface
      and evaluation. 

PMID- 25991286
TI  - Developing a mobile application for recording learning experiences in nursing
      practice.
AB  - OBJECTIVE: In complex clinical on-the-job training a seamless and target-oriented
      incorporation is crucial to assure a good medical care. The reliable transmission
      of specific and relevant facts, besides education knowledge, is a key factor to
      ensure sustainable quality in care processes. MATERIALS AND METHODS: We present
      the clinical field study WITRA care. A possible way to capture hidden clinical
      care knowledge with assistance of mobile devices will be described. RESULTS:
      Basic functions to collect learning experiences with mobile devices as well as a
      secure and confidential manner to support a reliable transmission procedure in
      the hospital network area are implemented. A user experience questionnaire and a
      semi-standardized interview illustrate first positive acceptance evaluations and
      time-saving effects. DISCUSSION AND CONCLUSION: With mobile devices, tacit
      knowledge gaps can be tapped in a clinical care unit. The study provided first
      insights and proved its feasibility in general. However, advanced problems and
      questions arose and will be considered in the future.

PMID- 25991287
TI  - Client-side Medical Image Colorization in a Collaborative Environment.
AB  - The paper presents an application related to collaborative medicine using a
      browser based medical visualization system with focus on the medical image
      colorization process and the underlying open source web development technologies
      involved. Browser based systems allow physicians to share medical data with their
      remotely located counterparts or medical students, assisting them during patient
      diagnosis, treatment monitoring, surgery planning or for educational purposes.
      This approach brings forth the advantage of ubiquity. The system can be accessed
      from a any device, in order to process the images, assuring the independence
      towards having a specific proprietary operating system. The current work starts
      with processing of DICOM (Digital Imaging and Communications in Medicine) files
      and ends with the rendering of the resulting bitmap images on a HTML5 (fifth
      revision of the HyperText Markup Language) canvas element. The application
      improves the image visualization emphasizing different tissue densities. 

PMID- 25991288
TI  - A user-editable web-based platform to streamline clinical information flow.
AB  - Frequent turnover of staff in medical clinics creates challenges in the
      maintenance of clinical protocols, workflows, and information management. Care
      coordination between providers in such a setting can be complex; disruptions in
      communication may lead to poorer health outcomes and patient satisfaction.
      Furthermore, protocols change frequently in response to new guidelines, which
      demands rapid updates to maintain compliance. To address these challenges, we
      developed an intuitive, end-user editable web-based knowledge management system
      optimized for use on mobile devices. The resulting system served as a point of
      care information storage and retrieval tool that providers can reference quickly
      for operational tasks. Since launch, the platform has allowed our clinic to
      consolidate knowledge banks, standardize staff training, and streamline
      information flow during clinic, and is now used extensively by clinic staff.
      During a one-year period, 175 new pages have been created and 1686 edits have
      been submitted by users. We posit that a mobile platform for clinical information
      flow management has significant potential to improve information maintenance and
      facilitate transfer of up-to-date clinical protocols to new personnel. 

PMID- 25991289
TI  - Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics.
AB  - Metformin is a commonly prescribed diabetes medication whose mechanism of action
      is poorly understood. In this study we utilized EHR-linked biobank data to
      elucidate the impact of genomic variation on glycemic response to metformin. Our
      study found significant gene- and SNP-level associations within the beta-2
      subunit of the heterotrimeric adenosine monophosphate-activated protein kinase
      complex. Using EHR phenotypes where were able to add additional clarity to
      ongoing metformin pharmacogenomic dialogue. 

PMID- 25991290
TI  - A Cloud Based Real-Time Collaborative Platform for eHealth.
AB  - For more than a decade, the eHealth initiative has been a government concern of
      many countries. In an Electronic Health Record (EHR) System, there is a need for
      sharing the data with a group of specialists simultaneously. Collaborative
      platforms alone are just a part of a solution, while a collaborative platform
      with parallel editing capabilities and with synchronized data streaming are
      stringently needed. In this paper, the design and implementation of a
      collaborative platform used in healthcare is introduced by describing the high
      level architecture and its implementation. A series of eHealth services are
      identified and usage examples in a healthcare environment are given. 

PMID- 25991291
TI  - PyMedTermino: an open-source generic API for advanced terminology services.
AB  - The integration of terminologies is still a challenging problem in medical
      informatics research and software applications, due to the high number of
      heterogeneous terminologies. In this paper, we present a generic API (Application
      Programming Interface) for a multi-terminology multilingual terminology service,
      and PyMedTermino, its open-source implementation in Python with 5 terminological
      resources (ICD10, SNOMED CT, MedDRA, CDF, VCM iconic language) and the UMLS
      compendium. This service has been designed for research and educational purpose.
      It offers various advanced functionalities rarely present in terminology
      services. 

PMID- 25991292
TI  - Designing ETL Tools to Feed a Data Warehouse Based on Electronic Healthcare
      Record Infrastructure.
AB  - Aim of this paper is to propose a methodology to design Extract, Transform and
      Load (ETL) tools in a clinical data warehouse architecture based on the
      Electronic Healthcare Record (EHR). This approach takes advantages on the use of
      this infrastructure as one of the main source of information to feed the data
      warehouse, taking also into account that clinical documents produced by
      heterogeneous legacy systems are structured using the HL7 CDA standard. This
      paper describes the main activities to be performed to map the information
      collected in the different types of document with the dimensional model
      primitives. 

PMID- 25991371
TI  - Digital Healthcare Empowering Europeans. Preface.

PMID- 25991372
TI  - Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation
      of miR-21 via Wnt/beta-catenin signaling in glioblastoma.
AB  - Temozolomide (TMZ) has been widely used in the treatment of glioblastoma (GBM),
      although inherent or acquired resistance restricts the application. This study
      was aimed to evaluate the efficacy of sulforaphane (SFN) to TMZ-induced apoptosis
      in GBM cells and the potential mechanism. Biochemical assays and subcutaneous
      tumor establishment were used to characterize the function of SFN in TMZ-induced
      apoptosis. Our results revealed that beta-catenin and miR-21 were concordantly
      expressed in GBM cell lines, and SFN significantly reduced miR-21 expression
      through inhibiting the Wnt/beta-catenin/TCF4 pathway. Furthermore, down
      regulation of miR-21 enhanced the pro-apoptotic efficacy of TMZ in GBM cells.
      Finally, we observed that SFN strengthened TMZ-mediated apoptosis in a miR-21
      dependent manner. In conclusion, SFN effectively enhances TMZ-induced apoptosis
      by inhibiting miR-21 via Wnt/beta-catenin signaling in GBM cells. These findings
      support the use of SFN for potential therapeutic approach to overcome TMZ
      resistance in GBM treatment. Our studies indicate that sulforaphane (SFN)
      enhances temozolomide (TMZ)-induced apoptosis because of down-regulation of miR
      21 through Wnt/beta-catenin signaling in glioblastoma (GBM) cells. These findings
      demonstrate SFN could be considered as a potential adjuvant therapeutic agent in
      treating GBM patients combined with TMZ in the future to affect resistance
      emergence. The further explorations are essential for the clinical application of
      SFN in GBM patients, and our results reveal an important mechanism of SFN
      chemopreventive and chemotherapeutic activity. Chr17, chromosome 17.

PMID- 25991374
TI  - A giant molecular proton pump: structure and mechanism of respiratory complex I.
AB  - The mitochondrial respiratory chain, also known as the electron transport chain
      (ETC), is crucial to life, and energy production in the form of ATP is the main
      mitochondrial function. Three proton-translocating enzymes of the ETC, namely
      complexes I, III and IV, generate proton motive force, which in turn drives ATP
      synthase (complex V). The atomic structures and basic mechanisms of most
      respiratory complexes have previously been established, with the exception of
      complex I, the largest complex in the ETC. Recently, the crystal structure of the
      entire complex I was solved using a bacterial enzyme. The structure provided
      novel insights into the core architecture of the complex, the electron transfer
      and proton translocation pathways, as well as the mechanism that couples these
      two processes. 

PMID- 25991379
TI  - Does adjusting the pH of lidocaine reduce pain during injection?
AB  - BACKGROUND: Receiving local anaestethic injection is painful. A double-blinded
      randomised study with 32 healthy adult volunteers was performed, with the aim of
      investigating the effect of buffering lidocaine to reduce the pain during
      injection. METHODS: Each participant received two subcutaneous injections of 4.5
      ml lidocaine 1% on the lower left and right quadrants of the abdomen. One
      solution was plain lidocaine (pH 6.55) and the other was lidocaine buffered with
      sodium bicarbonate in a ratio of 9:1 (pH 7.30). After each injection the
      participant marked the pain experienced during the injection on a visual analogue
      scale (VAS; 0 = best, 100 = worst), in addition to verbally stating which
      injection they found was the least painful. RESULTS: A total of 20 stated that
      they preferred the buffered solution, while eight said that they preferred the
      unbuffered solution (p < 0.002). The mean VAS pain-score was 15 (SD = 12) for the
      buffered injections and 20 (SD = 12) for the unbuffered injections (p < 0.017).
      CONCLUSION: The conclusion is that the pain experienced during the injection of
      lidocaine can be significantly reduced by buffering the solution before
      injection.

PMID- 25991373
TI  - Live to die another way: modes of programmed cell death and the signals emanating
      from dying cells.
AB  - All life ends in death, but perhaps one of life's grander ironies is that it also
      depends on death. Cell-intrinsic suicide pathways, termed programmed cell death
      (PCD), are crucial for animal development, tissue homeostasis and pathogenesis.
      Originally, PCD was almost synonymous with apoptosis; recently, however,
      alternative mechanisms of PCD have been reported. Here, we provide an overview of
      several distinct PCD mechanisms, namely apoptosis, autophagy and necroptosis. In
      addition, we discuss the complex signals that emanate from dying cells, which can
      either trigger regeneration or instruct additional killing. Further advances in
      understanding the physiological roles of the various mechanisms of cell death and
      their associated signals will be important to selectively manipulate PCD for
      therapeutic purposes. 

PMID- 25991376
TI  - Discovering centromere proteins: from cold white hands to the A, B, C of CENPs.
AB  - The kinetochore is a complex molecular machine that directs chromosome
      segregation during mitosis. It is one of the most elaborate subcellular protein
      structures in eukaryotes, comprising more than 100 different proteins. Inner
      kinetochore proteins associate with specialized centromeric chromatin containing
      the histone H3 variant centromere protein A (CENP-A) in place of H3. Outer
      kinetochore proteins bind to microtubules and signal to delay anaphase onset when
      microtubules are absent. Since the first kinetochore proteins were discovered and
      cloned 30 years ago using autoimmune sera from patients with scleroderma-spectrum
      disease, much has been learnt about the composition, functions and regulation of
      this remarkable structure.

PMID- 25991380
TI  - Venous thromboembolism: patient awareness and education in the pre-operative
      assessment clinic.
AB  - Each year venous thromboembolism (VTE) causes up to 60,000 deaths in the UK, many
      resulting from hospital-acquired thromboses following elective surgery. National
      Institute for Health and Clinical Excellence (NICE) guidelines state that all
      elective surgical patients should receive verbal and written information pre
      operatively regarding the risks of developing VTE. This audit assessed elective
      surgical patient's prior awareness of VTE and examined how effective targeted
      patient education during the pre-operative assessment is in increasing this
      awareness. A 13 point questionnaire designed to assess a pre-operative patient's
      understanding of topics relating to VTE was provided to consecutive patients
      identified as being at risk of developing VTE at the end of their pre-operative
      assessment over a two-week period. A total of 68 questionnaires were completed.
      Provision of verbal and written information was poor (47 %, n = 32 and 47 %, n =
      32 respectively). Despite this, 71 % (n = 48) of patients were aware of the
      consequences of developing VTE. Many patients correctly identified surgery (71 %,
      n = 48), immobility (71 %, n = 48) and being overweight (68 %, n = 46) as risk
      factors, but not dehydration (47 %, n = 32). Lack of awareness regarding personal
      methods to reduce the risk of developing a VTE post-operatively (24 %, n = 16)
      and potential side-effects of medical prophylaxis (32 %, n = 22) were also
      identified. Many patients already possess an awareness of VTE, however, specific
      knowledge regarding its risk factors and methods of prevention is lacking.
      Provision of targeted written and verbal educational information during the pre
      operative assessment is an effective method of increasing a patient's awareness
      of these topics. Increased patient awareness may empower patients in their post
      operative recovery and enable them to make more informed decisions regarding VTE
      prophylaxis options.

PMID- 25991382
TI  - Changes in lower urinary tract symptoms and quality of life after salvage
      radiotherapy for biochemical recurrence of prostate cancer.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate chronologic changes
      in lower urinary tract symptoms (LUTS), health-related (HR) quality of life
      (QOL), and disease-specific QOL during the first 12 months after salvage
      radiotherapy (SRT) for biochemical recurrence of prostate cancer in patients who
      underwent radical prostatectomy. MATERIALS AND METHODS: In 81 patients who
      received SRT (70 Gy/35fr/7 weeks), International Prostate Symptom Score (IPSS),
      36-Item Short Form scores, and UCLA-Prostate Cancer Index (UCLA-PCI) were
      recorded before, during, and immediately after SRT, and 1-12 months after the
      completion of SRT. RESULTS: The total IPSS and storage symptom-related sum were
      significantly increased following initiation of SRT, and returned to the baseline
      6 months after SRT. For three of eight domains of HRQOL, and the physical
      component summary score showed transient deterioration in the period between
      completion of SRT and 1 month following SRT. The UCLA-PCI for urinary
      function/bother and bowel function/bother was affected until 1-6 months after
      SRT. CONCLUSIONS: This is the first report to concurrently evaluate detailed
      chronologic changes in LUTS and QOL in patients who received SRT. Knowledge of
      changes in LUTS and QOL outcomes associated with SRT may influence treatment
      recommendations and enable patients to make better-informed decisions.

PMID- 25991381
TI  - The CD4(+) AT2R(+) T cell subpopulation improves post-infarction remodelling and
      restores cardiac function.
AB  - Myocardial infarction (MI) is a major condition causing heart failure (HF). After
      MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin
      II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors
      (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link
      between RAS and cellular components of the immune response relying on a rodent
      model of HF as well as HF patients. Flow cytometric analyses showed an increase
      in the expression of CD4(+) AT2R(+) cells in the rat heart and spleen post
      infarction, but a reduction in the peripheral blood. The latter was also observed
      in HF patients. The frequency of rat CD4(+) AT2R(+) T cells in circulating blood,
      post-infarcted heart and spleen represented 3.8 +/- 0.4%, 23.2 +/- 2.7% and 22.6
      +/- 2.6% of the CD4(+) cells. CD4(+) AT2R(+) T cells within blood CD4(+) T cells
      were reduced from 2.6 +/- 0.2% in healthy controls to 1.7 +/- 0.4% in patients.
      Moreover, we characterized CD4(+) AT2R(+) T cells which expressed regulatory
      FoxP3, secreted interleukin-10 and other inflammatory-related cytokines.
      Furthermore, intramyocardial injection of MI-induced splenic CD4(+) AT2R(+) T
      cells into recipient rats with MI led to reduced infarct size and improved
      cardiac performance. We defined CD4(+) AT2R(+) cells as a T cell subset improving
      heart function post-MI corresponding with reduced infarction size in a rat MI
      model. Our results indicate CD4(+) AT2R(+) cells as a promising population for
      regenerative therapy, via myocardial transplantation, pharmacological AT2R
      activation or a combination thereof.

PMID- 25991383
TI  - Lampropedia puyangensis sp. nov., isolated from symptomatic bark of Populus *
      euramericana canker and emended description of Lampropedia hyalina (Ehrenberg
      1832) Lee et al. 2004.
AB  - A Gram-stain negative, Neisser-stain negative, aerobic, non-motile, non-spore
      forming, slimy, glossy bacterial strain with single or clustered coccoid cells
      and white colony colour, designated as 2-bin(T), was isolated from cankered bark
      tissue of Populus * euramericana. The strain was found to grow at 15-40  degrees
      C and pH 5-10, with an optimum of 30  degrees C and pH 8.0. The strain was found
      to be negative with respect to catalase and positive for oxidase activity,
      nitrate reduction and Voges-Proskauer reaction. Analysis of 16S rRNA gene
      sequence data indicated that the isolate belongs to the genus Lampropedia, having
      sequence similarity of 96.24 % with Lampropedia hyalina ATCC11041(T). DNA-DNA
      relatedness of strain 2-bin(T) with L. hyalina JCM 21380(T) was 26.7 +/- 4.6 %.
      The DNA G+C content of strain 2-bin(T) was determined to be 57 % and the major
      cellular fatty acids were identified as C16:0, C16:1 omega7c/C16:1 omega6c and
      C18:1 omega7c. The polar lipid profile of strain 2-bin(T) was found to contain
      diphosphatidylglycerol, a glycolipid, phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylglycerol, a phospholipid,
      phosphatidylmonomethylethanolamine and three unidentified lipids (L1, L2, L3).
      Based on molecular data and physiological and biochemical characteristics, strain
      2-bin(T) is considered to represent a novel species in the genus Lampropedia, for
      which the name Lampropedia puyangensis sp. nov. is proposed. The type strain is 2
      bin(T) (= CFCC 10925(T) = KCTC 32235(T)). 

PMID- 25991384
TI  - Investigations on the interactions between naphthalimide-based anti-tumor drugs
      and human serum albumin by spectroscopic and molecular modeling methods.
AB  - The interactions between the three kinds of naphthalimide-based anti-tumor drugs
      (NADA, NADB, NADC) and human serum albumin (HSA) under simulated physiological
      conditions were investigated by fluorescence spectroscopy, circular dichroism
      spectroscopy and molecular modeling. The results of the fluorescence quenching
      spectroscopy showed that the quenching mechanisms for different drugs were static
      and their affinity was in a descending order of NADA > NADB > NADC. The relative
      thermodynamic parameters indicated that hydrophobic force was the predominant
      intermolecular force in the binding of NAD to HSA, while van der Waals
      interactions and hydrogen bonds could not be ignored. The results of site marker
      competitive experiment confirmed that the binding site of HSA primarily took
      place in site I. Furthermore, the molecular modeling study was consistent with
      these results. The study of circular dichroism spectra demonstrated that the
      presence of NADs decreased the alpha-helical content of HSA and induced the
      change of the secondary structure of HSA.

PMID- 25991385
TI  - The effect of different types of insoles or shoe modifications on medial loading
      of the knee in persons with medial knee osteoarthritis: a randomised trial.
AB  - Many conservative treatments exist for medial knee osteoarthritis (OA) which aims
      to reduce the external knee adduction moment (EKAM). The objective of this study
      was to determine the difference between different shoes and lateral wedge insoles
      on EKAM, knee adduction angular impulse (KAAI), external knee flexion moment,
      pain, and comfort when walking in individuals with medial knee OA. Seventy
      individuals with medial knee OA underwent three-dimensional walking gait analysis
      in five conditions (barefoot, control shoe, typical wedge, supported wedge, and
      mobility shoe) with pain and comfort recorded concurrently. The change in EKAM,
      KAAI, external knee flexion moment, pain, and comfort were assessed using
      multiple linear regressions and pairwise comparisons. Compared with the control
      shoe, lateral wedge insoles and barefoot walking significantly reduced early
      stance EKAM and KAAI. The mobility shoe showed no effect. A significant reduction
      in latter stance EKAM was seen in the lateral wedge insoles compared to the other
      conditions, with only the barefoot condition reducing the external knee flexion
      moment. However, the mobility shoe showed significant immediate knee pain
      reduction and improved comfort scores. Different lateral wedge insoles show
      comparable reductions in medial knee loading and in our study, the mobility shoe
      did not affect medial loading.

PMID- 25991386
TI  - [Oncofertility and breast cancer: Where have we come from, where are we going?].
AB  - BACKGROUND: Focusing on the current context of national and international
      recommendations, techniques development to evaluate and preserve fertility and
      patients' claims, this study aims to make a survey about the management of
      patients' breast cancer regarding oncofertility. METHODS: Retrospective and
      analytic study of medical practices at Bergonie Institute of health professionals
      (medical oncologists, surgical oncologists, nurses) dedicated to the care of non
      disseminated breast cancer patients younger than 37, needing medical treatment.
      RESULTS: The number of participants was 230. The most interested practitioners in
      fertility theme are those of multidisciplinary consultation and surgeons
      (P<0.001), with an increasing interest during last years (P<0.05). The
      information about hypofertilizing risks of treatments are delivered most of the
      time by oncologists (57.7%). The motherhood project is expressed by 11 patients
      (4.9%) before treatment, only 4 of them receive information on the risks and 49
      patients (21.7%) during follow-up. Only 24 patients (48% of the 49) are
      encouraged for motherhood. CONCLUSION: To satisfy patients' requests, several
      improvements have to be made regarding the patients' information, the health
      professionals' awareness and care coordination.

PMID- 25991388
TI  - Increased range of ultrasonic guided wave testing of overhead transmission line
      cables using dispersion compensation.
AB  - Overhead Transmission Line (OVTL) cables can experience structural defects and
      are, therefore, inspected using Non-Destructive Testing (NDT) techniques.
      Ultrasonic Guided Waves (UGW) is one NDT technique that has been investigated for
      inspection of these cables. For practical use, it is desirable to be able to
      inspect as long a section of cable as possible from a single location. This paper
      investigates increasing the UGW inspection range on Aluminium Conductor Steel
      Reinforced (ACSR) cables by compensating for dispersion using dispersion curve
      data. For ACSR cables, it was considered to be difficult to obtain accurate
      dispersion curves using modelling due to the complex geometry and unknown
      coupling between wire strands. Group velocity dispersion curves were, therefore,
      measured experimentally on an untensioned, 26.5m long cable and a method of
      calculating theoretical dispersion curves was obtained. Attenuation and
      dispersion compensation were then performed for a broadband Maximum Length
      Sequence (MLS) excitation signal. An increase in the Signal to Noise Ratio (SNR)
      of about 4-8dB compared to that of the dispersed signal was obtained. However,
      the main benefit was the increased ability to resolve the individual echoes from
      the end of the cable and an introduced defect in the form of a cut, which was 7
      to at least 13dB greater than that of the dispersed signal. Five echoes were able
      to be clearly detected using MLS excitation signal, indicating the potential for
      an inspection range of up to 130m in each direction. To the best of the authors
      knowledge, this is the longest inspection range for ACSR cables reported in the
      literature, where typically cables, which were only one or two meter long, have
      been investigated previously. Narrow band tone burst and Hann windowed tone burst
      excitation signal also showed increased SNR and ability to resolve closely spaced
      echoes. 

PMID- 25991389
TI  - Thermally triggered degradation of transient electronic devices.
AB  - Thermally triggered transient electronics using wax-encapsulated acid, which
      enable rapid device destruction via acidic degradation of the metal electronic
      components are reported. Using a cyclic poly(phthalaldehyde) (cPPA) substrate
      affords a more rapid destruction of the device due to acidic depolymerization of
      cPPA. 

PMID- 25991390
TI  - Quantitative metabolic profiling of NMR spectral signatures of branched chain
      amino acids in blood serum.
AB  - Branched Chain Amino Acids (BCAAs) are related to different aspects of diseases
      like pathogenesis, diagnosis and even prognosis. While in some diseases, levels
      of all the BCAAs are perturbed; in some cases, perturbation occurs in one or two
      while the rest remain unaltered. In case of ischemic heart disease, there is an
      enhanced level of plasma leucine and isoleucine but valine level remains
      unaltered. In 'Hypervalinemia', valine is elevated in serum and urine, but not
      leucine and isoleucine. Therefore, identification of these metabolites and
      profiling of individual BCAA in a quantitative manner in body-fluid like blood
      plasma/serum have long been in demand. (1)H NMR resonances of the BCAAs overlap
      with each other which complicates quantification of individual BCAAs. Further,
      the situation is limited by the overlap of broad resonances of lipoprotein with
      the resonances of BCAAs. The widely used commercially available kits cannot
      differentially estimate the BCAAs. Here, we have achieved proper identification
      and characterization of these BCAAs in serum in a quantitative manner employing a
      Nuclear Magnetic Resonance-based technique namely T2-edited Correlation
      Spectroscopy (COSY). This approach can easily be extended to other body fluids
      like bile, follicular fluids, saliva, etc. 

PMID- 25991391
TI  - A Nurse Practitioner Clinic: A Novel Approach to Supporting Patients Following
      Heart Valve Surgery.
AB  - BACKGROUND: Valvular heart disease is an important healthcare issue and its
      impacts are increasing. Following valve surgery, traditional models of care
      involve medical personnel, however, significant gaps in guideline adherence and
      delays in follow-up have been reported. Internationally, there is increasing
      evidence that specialist nurses can function in a variety of clinical settings
      and improve patient management. METHODS: In 2009, a nurse practitioner clinic to
      support patients following valve surgery was established. We used a retrospective
      clinical audit and clinical review with descriptive statistics to describe the
      development of the clinic and to provide guidance for other services for model of
      care development. RESULTS: Over four years, 462 patients have been reviewed at
      least once, with over half having multiple assessments, 37% had rheumatic heart
      disease. These patients were 20 years younger and more likely to be women, non
      European, current smokers and have atrial fibrillation. All patients received a
      focussed lifestyle, rheumatic, thromboembolic and endocarditis risk and symptom
      review with tailored support, advice and referral where appropriate. Four percent
      were referred back to a cardiologist for early evidence of valve dysfunction and
      a further 1.5% required urgent admission for unstable symptoms. CONCLUSION: The
      nurse practitioner clinic offers a systematic approach to promoting guideline
      adherence post valvular surgery. Important clinical symptoms and differences in
      health needs were identified and were actioned appropriately.

PMID- 25991392
TI  - Dynamic four-dimensional computed tomography (4D CT) imaging for re-entry risk
      assessment in re-do sternotomy - first experience.
AB  - BACKGROUND: Repeat cardiac surgeries are well known to have higher rates of
      complications, one of the important reasons being injuries associated with re-do
      sternotomy. Routine imaging with CT can help to minimise this risk by pre
      operatively assessing the anatomical relation between the sternum and the
      underlying cardiovascular structures, but is limited by its inability to
      determine the presence and severity of functional tethering and adhesions between
      these structures. However, with the evolution of wide area detector MD CT
      scanners, it is possible to assess the presence of tethering using the dynamic
      four-dimensional CT (4D CT) imaging technique. METHODS: Nineteen patients
      undergoing re-do cardiac surgery were pre-operatively imaged using dynamic 4D CT
      during regulated respiration. The datasets were assessed in cine mode for
      presence of differential motion between sternum and underlying cardiovascular
      structures which indicates lack of significant tethering. RESULTS: Overall, there
      was excellent correlation between preoperative imaging and intraoperative
      findings. The technique enabled our surgeons to meticulously plan the procedures
      and to avoid re-entry related injuries. CONCLUSIONS: Our initial experience shows
      that dynamic 4D CT is useful in risk stratification prior to re-do sternotomy by
      determining the presence or absence of tethering between sternum and underlying
      structures based on assessment of differential motion. Furthermore we determined
      the technique to be superior to non-dynamic assessment of retrocardiac tethering.

PMID- 25991393
TI  - Tracheo-bronchoplastic procedures for NSCLC: single-centre experience.
AB  - BACKGROUND: The purpose of this study was to assess operative mortality,
      morbidity, and long-term results of the totality of sleeve resections performed
      at our institutions over the last eight years, including sleeve lobectomies (SL),
      carinoplasties with total lung sparing (CP) and sleeve pneumonectomies (SP).
      METHODS: A retrospective review of all the patients who underwent a tracheo
      bronchial resection for bronchial cancer between 2004 and 2012 was undertaken.
      Bronchial sleeve resections and combined bronchial and vascular sleeve resections
      were described. RESULTS: The resulting group studied was 22 patients. SL and SP
      had a perioperative mortality rate of 7.1% and 28.5% respectively; morbidity
      rates were 21.4% for SL and 42.8% for SP. Global one-year and three-year survival
      was 75% and 63% respectively. One-year survival was 84% for SL and 53% for SP;
      three-year survival rate was 65% and 35% respectively (p=0.24). The absence of
      nodal metastatic involvement was associated with a better outcome with a three
      year survival rate of 69% in the N0 group vs a 36% rate in the N+ group.
      CONCLUSIONS: Sleeve resection procedures achieved satisfactory local control of
      the tumour in our experience even in patients with preoperative contraindication
      to pneumonectomy, with acceptable mortality and morbidity rates.

PMID- 25991394
TI  - Utility of Routine Exercise Stress Testing among Intermediate Risk Chest Pain
      Patients Attending an Emergency Department.
AB  - BACKGROUND: To assess the utility of routine exercise stress testing (EST) in
      patients at intermediate risk of acute coronary syndrome (ACS) according to the
      Heart Foundation of Australia/Cardiac Society of Australia and New Zealand
      (HFA/CSANZ) guidelines. METHOD: Prospective observational study of patients
      presenting to the Emergency Department (ED) with chest pain suggestive of ACS
      between November 2008 and July 2014. Participants included 1205 patients who
      presented to the ED with chest pain suggestive of ACS and who met the HFA/CSANZ
      intermediate risk criteria. The outcome was diagnosis of ACS occurring on
      presentation or within 30 days of presentation to the ED. ACS included acute
      myocardial infarction and unstable angina pectoris. RESULTS: Twenty (1.66%) of
      the intermediate risk patients were diagnosed with ACS. Of the 777 patients who
      underwent EST, eight had ACS. EST identified all ACS cases except for one patient
      with a negative test, who was ultimately diagnosed with ACS following
      angiography. 164 patients deemed inappropriate to undergo EST underwent an
      alternative form of objective testing, of which 12 were positive for ACS. 264
      patients underwent no objective testing. CONCLUSION: EST stratifies intermediate
      risk patients to a near zero short-term risk of ACS. However, the overall yield
      of EST within this group of patients is extremely low. Intermediate risk patients
      with normal zero and six hour biomarkers have a very low probability of ACS, and
      over half of these patients ultimately diagnosed with ACS in this group were
      deemed unsuitable for EST anyway. Future research should focus on the
      identification of patients who do not require EST and the inclusion of routine
      EST within the HFA/CSANZ guidelines should be reconsidered.

PMID- 25991395
TI  - A multicenter study of 30 days complications after deceased donor liver
      transplantation in the model for end-stage liver disease score era.
AB  - Knowledge of risk factors for posttransplant complications is likely to improve
      patient outcomes. Few large studies of all early postoperative complications
      after deceased donor liver transplantation (DDLT) exist. Therefore, we conducted
      a retrospective, cohort study of 30-day complications, their risk factors, and
      the impact on outcomes after DDLT. Three centers contributed data for 450 DDLTs
      performed from January 2005 through December 2009. Data included donor,
      recipient, transplant, and outcome variables. All 30-day postoperative
      complications were graded by the Clavien-Dindo system. Complications per patient
      and severe (>= grade III) complications were primary outcomes. Death within 30
      days, complication occurrence, length of stay (LOS), and graft and patient
      survival were secondary outcomes. Multivariate associations of risk factors with
      complications and complications with LOS, graft survival, and patient survival
      were examined. Mean number of complications/patient was 3.3 +/- 3.9. At least 1
      complication occurred in 79.3%, and severe complications occurred in 62.8% of
      recipients. Mean LOS was 16.2 +/- 22.9 days. Graft and patient survival rates
      were 84% and 86%, respectively, at 1 year and 74% and 76%, respectively, at 3
      years. Hospitalization, critical care, ventilatory support, and renal replacement
      therapy before transplant and transfusions during transplant were the significant
      predictors of complications (not the Model for End-Stage Liver Disease score).
      Both number and severity of complications had a significant impact on LOS and
      graft and patient survival. Structured reporting of risk-adjusted complications
      rates after DDLT is likely to improve patient care and transplant center
      benchmarking. Despite the accomplished reductions in transfusions during DDLT,
      opportunities exist for further reductions. With increasing transplantation of
      sicker patients, reduction in complications would require multidisciplinary
      efforts and institutional commitment. Pretransplant risk characteristics for
      complications must factor in during payer contracting.

PMID- 25991396
TI  - Concomitant methotrexate and tacrolimus augment the clinical response to
      abatacept in patients with rheumatoid arthritis with a prior history of
      biological DMARD use.
AB  - This observational retrospective study examined whether abatacept efficacy could
      be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients
      with rheumatoid arthritis (RA) who experienced failure with prior biological
      disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic
      efficacy is difficult to achieve. All patients with a prior biological DMARD
      history who were treated with abatacept for 52 weeks and registered in a Japanese
      multicentre registry were included. Clinical efficacy and safety of abatacept
      according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and
      TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was
      observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5
      vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC
      groups had a significantly higher proportion of patients who achieved low disease
      activity (LDA) within 52 weeks compared with the respective baselines, while no
      significant change was observed in the ABT-mono group. A higher proportion of
      patients in the ABT-TAC group achieved EULAR moderate response compared with the
      ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic
      regression analysis revealed that concomitant TAC use was independently
      associated with the achievement of LDA and EULAR response at 52 weeks, while
      concomitant MTX use was not. Concomitant TAC use may offer a suitable option for
      RA patients treated with abatacept after prior biological DMARD failure, likely
      because both abatacept and TAC affect T cell activation. 

PMID- 25991397
TI  - Patient and clinical characteristics associated with gout flares in an integrated
      healthcare system.
AB  - Gout flares have been challenging to identify in retrospective databases due to
      gout flares not being well documented by diagnosis codes, making it difficult to
      conduct accurate database studies. Previous studies have used different
      algorithms, and in this study, we used a computer-based method to identify gout
      flares. The objectives of this study were to identify gout flares in gout
      patients newly initiated on urate-lowering therapy and evaluate factors
      associated with a patient experiencing gout flares after starting drug treatment.
      This was a retrospective cohort study identifying gout patients newly initiated
      on a urate-lowering therapy (ULT) during the study time period of January 1, 2007
      December 31, 2010. The index date was the first dispensed ULT prescription during
      the study time period. Patients had to be >=18 years of age on index date, have
      no history of prior ULT prescription during 12 months before index date, and were
      required to have 12 months of continuous membership with drug benefit during pre
      /post-index. Electronic chart notes were reviewed to identify gout flares; these
      reviews helped create a validated computer-based method to further identify
      patients with gout flares and were categorized into 0 gout flares, 1-2 gout
      flares, and >=3 gout flares during the 12 months post-index period. Multivariable
      logistic regression was used to examine patient and clinical factors associated
      with gout flares during the 12-month follow-up period. There were 8905 patients
      identified as the final cohort and 68 % of these patients had one or more gout
      flares during the 12-month follow-up: 2797 patients (31 %) had 0 gout flares,
      4836 (54 %) had 1-2 gout flares, and 1272 patients (14 %) had >=3 gout flares.
      Using a multivariate regression analyses, factors independently associated with 1
      2 gout flares and >=3 gout flares versus no gout flares were similar, however,
      with slight differences, such as younger patients were more likely to have 1-2
      gout flares and patients >=65 years of age had >=3 gout flares. Factors such as
      male gender, not attaining sUA goal, having >=3 comorbidities, diuretics use, no
      changes in initial ULT dose, and not adhering to ULT all were associated with
      gout flares versus no gout flares. Using a new method to identify gout flares, we
      had the opportunity to compare our findings with the previous studies. Our study
      findings echo other previous studies where older patients, male, diuretics,
      having a greater number of comorbidities, and non-adherence are more likely to
      have more gout flares during the first year of newly initiating ULT. There is an
      unmet need for patients with gout to be educated and managed more closely,
      especially during the first year.

PMID- 25991398
TI  - Vitamin D levels in juvenile idiopathic arthritis from an equatorial region.
AB  - We aimed to describe the serum levels of 25-hydroxyvitamin D (25OHD) in juvenile
      idiopathic arthritis (JIA) patients living in a low-latitude (3 degrees 43'S)
      region. Fifty JIA patients, 31 (62 %) female, seen between May 2012 and April
      2013 in the northeast of Brazil had clinical data and serum collected for
      determination of 25OHD and parathyroid hormone (PTH) using a chemiluminescent
      ELISA; 20 age- and sex-matched controls were used for comparison. Mean age was
      13.4 +/- 4 years. Twenty-five (50 %), 15 (30 %), 4 (8 %), 4 (8 %), and 2 (4 %)
      patients were of the polyarticular, oligoarticular, systemic, enthesitis-related,
      and undifferentiated categories, respectively. Mean 25OHD was 31.6 +/- 10 and
      30.4 +/- 5.7 ng/mL in patients and controls (P > 0.05), respectively; PTH was
      normal in JIA and controls; 25OHD was similar regardless of JIA category, disease
      activity, or severity measured by JADAS-27, CHAQ, or presence of joint
      deformities. Twenty-six (52 %), 20 (40 %), and 4 (8 %) patients were considered
      to have optimal, sufficient, and deficient 25OHD levels, respectively, whereas 11
      (52 %) and 10 (48 %) controls had optimal and sufficient 25OHD. Ethnicity, body
      mass index, seasonal variation, and use of steroids did not influence 25OHD
      levels. This is the first study on 25OHD levels in JIA patients living in a low
      latitude region, showing the lowest prevalence of vitamin D deficiency ever
      reported. Serum 25OHD was similar in JIA and controls and did not vary regardless
      of JIA category or severity. 

PMID- 25991399
TI  - Assessment of serum levels of osteopontin, selenium and prolactin in patients
      with psoriasis compared with healthy controls, and their association with
      psoriasis severity.
AB  - BACKGROUND: The association between psoriasis and cardiovascular diseases is well
      documented, but the underlying mechanisms remain unknown. Overexpression of
      osteopontin (OPN) has been reported in the plasma of patients with psoriasis,
      with increased cardiovascular risk factors in these patients. Selenium compounds
      are effective in downregulating OPN expression. OBJECTIVE: We investigated the
      levels of OPN, selenium and prolactin (PRL) in psoriasis, and their association
      with metabolic status in patients to identify a possible link between these
      markers and observed comorbidities. METHODS: Plasma samples from 40 patients with
      psoriasis and 40 age- and sex-matched healthy controls (HCs) were collected for
      ELISA. The clinical significance of plasma OPN, selenium and PRL levels in
      patients compared with controls was analysed in relation to metabolic disorders.
      RESULTS: There was no significant difference in median serum selenium levels
      between the two groups. Serum levels of PRL were not significantly different from
      those of HCs, but levels of OPN were significantly higher in patients with
      psoriasis than in HCs. CONCLUSIONS: High plasma OPN is a predictor for occurrence
      of psoriasis. Our study showed that serum selenium and PRL were not decreased in
      patients with psoriasis, but there was a negative statistically significant
      correlation between OPN and selenium in all participants.

PMID- 25991400
TI  - Arterial Stiffness and Peripheral and Central Blood Pressure in Patients With
      Sickle Cell Disease.
AB  - Blood pressure (BP) in patients with sickle cell disease (SCD) has been reported
      to be lower than in persons in the general population. Data on arterial
      stiffness, which is an important risk factor for the progression of BP, are
      inconclusive for this patient population. Forty-five adult patients with SCD and
      40 controls matched for sex, age, and body mass index were studied. Brachial
      systolic BP (SBP) and diastolic BP (DBP) were significantly lower in the patient
      group (SBP 115.1+/-13.8 mm Hg vs 121.9+/-11.3 mm Hg and DBP 68.5+/-8.0 mm Hg vs
      80.6+/-9.1 mm Hg, P<.05, respectively). Augmentation index (AIx), however, was
      significantly higher in SCD patients compared with healthy controls (24.9+/-9.6
      for patients vs 12.4+/-10.8 for controls, P<.001), while carotid femoral pulse
      wave velocity was comparable between the two groups. The study shows that
      mechanisms other than arterial elasticity are involved in the low BP phenotype of
      patients with SCD. 

PMID- 25991401
TI  - What do patients with scans without evidence of dopaminergic deficit (SWEDD)
      have? New evidence and continuing controversies.
AB  - The term SWEDD (scans without evidence for dopaminergic deficit) refers to the
      absence, rather than the presence, of an imaging abnormality in patients
      clinically presumed to have Parkinson's disease (PD). However, such a term has
      since been widely used in the medical literature, even as a diagnostic label.
      While many authors have suggested that different disorders of PD lookalikes may
      account for a proportion of SWEDD cases, others have claimed that some of them
      may have a benign subtype of PD. Thus, there has been ensuing controversy and
      confusion and the use of this term continues without clarity of what it
      represents. We have systematically reviewed all the studies involving patients
      with SWEDD with the aim of shedding light on what these patients actually have.
      It becomes clear from this systematic review that while most 'SWEDD' cases are
      due to a clinical misdiagnosis of PD, there exists a small proportion of patients
      with SWEDD who may have PD on the basis of a positive levodopa response, clinical
      progression, imaging and/or genetic evidence. The latter challenge the seemingly
      incontrovertible relationship between dopaminergic tracer binding and the
      diagnosis of nigrostriatal parkinsonism, particularly PD. Patients with SWEDD are
      unlikely to reflect a single clinical entity and we suggest that the term SWEDD
      should be abandoned. 

PMID- 25991403
TI  - Bisulfite-Based DNA Methylation Analysis from Recent and Archived Formalin-Fixed,
      Paraffin Embedded Colorectal Tissue Samples.
AB  - We aimed to test the applicability of formalin-fixed and paraffin-embedded (FFPE)
      tissue samples for gene specific DNA methylation analysis after using two
      commercially available DNA isolation kits. Genomic DNA was isolated from 5
      colorectal adenocarcinomas and 5 normal adjacent tissues from "recent", collected
      within 6 months, and "archived", collected more than 5 years ago, FFPE tissues
      using either High Pure FFPET DNA Isolation kit or QIAamp DNA FFPE Tissue kit. DNA
      methylation analysis of MAL, SFRP1 and SFRP2 genes, known to be hypermethylated
      in CRC, was performed using methylation-sensitive high resolution melting (MS
      HRM) analysis and sequencing. QIAamp (Q) method resulted in slightly higher
      recovery in archived (HP: 1.22 +/- 3.18 MUg DNA; Q: 3.00 +/- 4.04 MUg DNA) and
      significantly (p < 0.05) higher recovery in recent samples compared to High Pure
      method (HP) (HP: 4.10 +/- 2.91 MUg DNA; Q: 11.51 +/- 7.50 MUg DNA). Both
      OD260/280 and OD260/230 ratios were lower, but still high in the High Pure
      isolated archived and recent samples compared to those isolated with QIAamp.
      Identical DNA methylation patterns were detected for all 3 genes tested by MS-HRM
      with both isolation kits in the recent group. However, despite of higher DNA
      recovery in QIAamp slightly more reproducible methylation results were obtained
      from High Pure isolated archived samples. Sequencing confirmed DNA
      hypermethylation in CRCs. In conclusion, reproducible DNA methylation patterns
      were obtained from recent samples using both isolation kits. However, long term
      storage may affect the reliability of the results leading to moderate differences
      between the efficiency of isolation kits.

PMID- 25991402
TI  - NMDA receptor binding in focal epilepsies.
AB  - OBJECTIVE: To demonstrate altered N-methyl-d-aspartate (NMDA) receptor
      availability in patients with focal epilepsies using positron emission tomography
      (PET) and [(18)F]GE-179, a ligand that selectively binds to the open NMDA
      receptor ion channel, which is thought to be overactive in epilepsy. METHODS:
      Eleven patients (median age 33 years, 6 males) with known frequent interictal
      epileptiform discharges had an [(18)F]GE-179 PET scan, in a cross-sectional
      study. MRI showed a focal lesion but discordant EEG changes in two, was non
      localising with multifocal EEG abnormalities in two, and was normal in the
      remaining seven patients who all had multifocal EEG changes. Individual patient
      [(18)F]GE-179 volume-of-distribution (VT) images were compared between individual
      patients and a group of 10 healthy controls (47 years, 7 males) using Statistical
      Parametric Mapping. RESULTS: Individual analyses revealed a single cluster of
      focal VT increase in four patients; one with a single and one with multifocal MRI
      lesions, and two with normal MRIs. Post hoc analysis revealed that, relative to
      controls, patients not taking antidepressants had globally increased [(18)F]GE
      179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had
      globally reduced [(18)F]GE-179 VT (-29%; p<0.002). There were no focal
      abnormalities common to the epilepsy group. CONCLUSIONS: In patients with focal
      epilepsies, we detected primarily global increases of [(18)F]GE-179 VT consistent
      with increased NMDA channel activation, but reduced availability in those taking
      antidepressant drugs, consistent with a possible mode of action of this class of
      drugs. [(18)F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of
      11 patients, with difficult to localise and treat focal epilepsy.

PMID- 25991405
TI  - The role of mitochondria in statin-induced myopathy.
AB  - BACKGROUND: Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease
      plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity
      and mortality. They can also exert adverse effects, mostly affecting skeletal
      muscle, ranging from mild myalgia to rhabdomyolysis. MATERIALS AND METHODS: Based
      on a PubMed search until December 2014, this review summarizes studies on statin
      effects on muscle mitochondrial morphology and function in the context of
      myopathy. RESULTS: Possible mechanisms of statin-induced myopathy include lower
      cholesterol synthesis and production of prenylated proteins, reduced dolichols
      and increased atrogin-1 expression. Statin-treated patients frequently feature
      decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might
      impair mitochondrial function. In cell cultures, statins diminish muscle oxygen
      consumption, promote mitochondrial permeability transient pore opening and
      generate apoptotic proteins. Animal models confirm the statin-induced decrease in
      muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human
      studies yield contradictory results, with decreased CoQ10, elevated lipids,
      decreased enzyme activities in muscle and impaired maximal oxygen uptake in
      several but not all studies. Some patients are susceptible to statin-induced
      myopathy due to variations in genes encoding proteins involved in statin uptake
      and biotransformation such as the solute carrier organic anion transporter family
      member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for
      carnitine palmitoyltransferase II deficiency and McArdle disease also present
      with higher prevalence of statin-induced myopathy. CONCLUSIONS: Despite the
      widespread use of statins, the pathogenesis of statin-induced myopathy remains
      unclear, requiring prospective randomized controlled trials with intensive
      phenotyping also for identifying strategies for its risk assessment, prevention
      and treatment.

PMID- 25991406
TI  - Recombinant growth hormone therapy for cystic fibrosis in children and young
      adults.
AB  - BACKGROUND: Cystic fibrosis is an inherited condition causing disease most
      noticeably in the lungs, digestive tract and pancreas. People with cystic
      fibrosis often have malnutrition and growth delay. Adequate nutritional
      supplementation does not improve growth optimally and hence an anabolic agent,
      recombinant growth hormone, has been proposed as a potential intervention.
      OBJECTIVES: To evaluate the effectiveness and safety of recombinant human growth
      hormone therapy in improving lung function, quality of life and clinical status
      of children and young adults with cystic fibrosis. SEARCH METHODS: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register
      comprising references identified from comprehensive electronic database searches
      and handsearches of relevant journals and abstract books of conference
      proceedings. Date of latest search: 11 February 2015.We conducted a search of
      relevant endocrine journals and proceedings of the Endocrinology Society meetings
      using Scopus and Proceedings First. Date of latest search: 04 March 2015.
      SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of all
      preparations of recombinant growth hormone compared to either no treatment, or
      placebo, or each other at any dose (high-dose and low-dose) or route and for any
      duration, in children or young adults aged up to 25 years diagnosed with cystic
      fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS: Two
      authors independently screened papers, extracted trial details and assessed their
      risk of bias. MAIN RESULTS: Four controlled trials were included in this review
      (with 161 participants in total), each with an unclear risk of bias. Analysis of
      data obtained from these trials shows improvement in height for all comparisons,
      but improvements in weight and lean tissue mass were only reported in the
      comparison of standard dose recombinant growth hormone versus no treatment. One
      study showed moderate improvement at one time point in one parameter of pulmonary
      function tests, forced vital capacity (per cent predicted) when comparing
      standard dose recombinant growth hormone and no treatment, but there was no
      consistent benefit in lung function across all studies. Little evidence was found
      for improvement in quality of life. An improvement in fasting blood glucose
      levels was reported when comparing rhGH to placebo only. Exercise capacity
      improved in participants receiving standard dose recombinant growth hormone
      versus no treatment, but not for any other comparison. There is insufficient
      evidence to conclude any changes in hospitalisations, antibiotic use or
      significant adverse effects. AUTHORS' CONCLUSIONS: Recombinant growth hormone
      therapy is effective in improving the intermediate outcomes in height, weight and
      lean tissue mass when compared with no treatment. One measure of pulmonary
      function test showed moderate improvement at a single time point, but no
      consistent benefit was seen across all studies. No significant changes in quality
      of life, clinical status or side-effects were observed in this review. Long-term,
      well-designed randomised controlled trials of recombinant growth hormone therapy
      in people with cystic fibrosis are required prior to evaluation of human growth
      hormone treatment for routine use.

PMID- 25991407
TI  - Estimated hospitalizations attributed to norovirus and rotavirus infection in
      Canada, 2006-2010.
AB  - Enteric viruses including norovirus and rotavirus are leading causes of
      gastroenteritis in Canada. However, only a small number of clinical cases are
      actually tested for these pathogens leading to systematic underestimation of
      attributed hospitalizations in administrative databases. The objective of this
      analysis was to estimate the number of hospitalizations due to norovirus and
      rotavirus in Canada. Hospitalization records for acute gastroenteritis-associated
      discharges at all acute-care hospitals in Canada between 2006 and 2011 were
      analysed. Cause-unspecified gastroenteritis hospitalizations were modelled using
      age-specific negative binomial models with cause-specified gastroenteritis
      admissions as predictors. The coefficients from the models were used to estimate
      the number of norovirus and rotavirus admissions. The total annual
      hospitalizations for rotavirus were estimated to be between 4500 and 10 000.
      Total annual hospitalizations for norovirus were estimated to be between 4000 and
      11 000. The mean total annual cost associated with these hospitalizations was
      estimated to be at least $16 million for rotavirus and $21 million for norovirus
      (all figures in Canadian dollars). This study is the first comprehensive analysis
      of norovirus and rotavirus hospitalizations in Canada. These estimates provide a
      more complete assessment of the burden and economic costs of these pathogens to
      the Canadian healthcare system. 

PMID- 25991408
TI  - Electrophysiologic and Clinical Consequences of Left Atrial Anterior Wall Linear
      Ablation in Patients With Persistent Atrial Fibrillation.
AB  - OBJECTIVE: As an alternative to the mitral isthmus line (MIL), the left atrial
      anterior wall line (LAAWL) is effective for the treatment of perimitral flutter.
      This study evaluated the electrophysiologic and clinical outcomes of LAAWL versus
      MIL in patients with persistent atrial fibrillation (AF). METHODS: Two hundred
      patients with persistent AF were evenly randomized to the LAAWL and MIL groups.
      After confirming bidirectional block of the line, left atrial appendage (LAA)
      activation time and LA propagation pattern were assessed during sinus rhythm
      (SR). Transthoracic and transesophageal echocardiography (TTE and TEE) were
      performed at 12 months after ablation in patients who remained in stable SR.
      RESULTS: In the 74 patients with LAAWL conduction block relative to the 79 with
      MIL conduction block, LA propagation contour was markedly changed with delayed
      LAA potential (longer P-wave onset-to-LAA potential interval: 151.7 +/- 19.5 vs.
      67.8 +/- 18.3 milliseconds, P < 0.001); TTE peak A velocity was lower and LAA
      emptying wave was delayed in the LAAWL group compared with the MIL group;
      spontaneous echo contrast (SEC) detected in the LAAWL group was significantly
      higher than that in the MIL group (15.8% vs. 1.6%, p = 0.0004). During a mean
      follow-up period of 31.8 +/- 9.4 (22-57) months, there were 5 cases of stroke in
      the LAAWL group, which was significantly different from the MIL group (5% vs. 0%,
      P = 0.047). CONCLUSIONS: Complete linear lesions transecting the anterior LA were
      associated with a significant change in the SR propagation pattern with late
      activation of LAA. This might result in an increased risk of long-term thrombo
      embolism events.

PMID- 25991409
TI  - Targeted resequencing analysis of 31 genes commonly mutated in myeloid disorders
      in serial samples from myelodysplastic syndrome patients showing disease
      progression.

PMID- 25991410
TI  - DEVELOPING AN IPAD(r) APPLICATION FOR DATA COLLECTION IN A RHEUMATOLOGY RESEARCH
      CLINIC.
AB  - OBJECTIVES: Clinical research data are often collected on paper and later
      inputted onto an electronic database. This method is time consuming and
      potentially introduces errors. Therefore, to make primary data collection more
      efficient and less error prone we aimed to develop a touch-screen application for
      data collection in a psoriatic arthritis research clinic and compared it with the
      pre-existing paper-based system. METHODS: We developed a Web application using
      Java and optimized it for the iPad(r). It highlights missing fields for
      physicians in real time, and only permits submission of data collection form
      after corrections are made. For its evaluation, seven physicians participated,
      and before each patient visit they were randomly assigned paper or iPad(r) data
      entry. Number of errors, length of visit, and time between clinic visit and
      completion of data entry were measured. RESULTS: A total of 106 patients seen in
      the clinic who agreed to participate were randomly assigned to be evaluated by
      clinic physicians using the iPad(r) (fifty-three patients) or a paper protocol
      (fifty-three patients). On average, 3.34 omissions were found per paper form, of
      which 2.24 would have been detected on the iPad(r). The iPad(r) increased the
      mean patient encounter time from 37.2 minutes to 46.5 minutes, but eliminated
      delay between a clinic visit and its data entry. CONCLUSIONS: Entering data using
      the iPad(r) application makes the patient encounter slightly longer, but reduces
      "missing fields." It also eliminates the delay between clinic visit and data
      entry thus improving the efficiency of clinical data capture in a research
      setting.

PMID- 25991411
TI  - DNA-based identifications reveal multiple introductions of the vegetable
      leafminer Liriomyza sativae (Diptera: Agromyzidae) into the Torres Strait Islands
      and Papua New Guinea.
AB  - Leafmining flies (Diptera: Agromyzidae) can be serious economic pests of
      horticultural crops. Some genera such as Liriomyza are particularly problematic
      with numerous species, some of which are highly polyphagous (wide host range),
      which can only be confidently identified morphologically from adult males. In our
      study, DNA barcoding was employed to establish new locality records of the
      vegetable leafminer fly, Liriomyza sativae, from the islands of Torres Strait
      (Queensland, Australia) and the central highlands of Papua New Guinea (PNG).
      These records represent significant range extensions of this highly invasive
      plant pest. Specimens of immature leafminers (from leaf mines) were collected
      over a 5-year period during routine plant health surveys in ethanol or on FTA(r)
      filter paper cards, both methods proved effective at preserving and transporting
      insect DNA under tropical conditions, with FTA cards possessing some additional
      logistical benefits. Specimens were identified through sequencing two sections of
      the cytochrome oxidase I gene and the utility of each was assessed for the
      identification of species and intra-specific genetic lineages. Our study
      indicates that multiple haplotypes of L. sativae occur in PNG, while a different
      haplotype is present in the Torres Strait, with genetic regionalization between
      these areas apart from a single possible instance - one haplotype 'S.7' appears
      to be common between these two regions - interestingly this has also been the
      most common haplotype detected in previous studies of invasive L. sativae
      populations. The DNA barcoding methods employed here not only identified multiple
      introductions of L. sativae, but also appear generally applicable to the
      identification of other agromyzid leafminers (Phytomyzinae and Agromyzinae) and
      should decrease the likelihood of potentially co-amplifying internal hymenopteran
      parasitoids. Currently, L. sativae is still not recorded from the Australian
      mainland; however, further sampling of leafminer flies from Northern Australia
      and surrounding areas is required, as surveillance for possible Liriomyza
      incursions, as well as to characterize endemic species with which Liriomyza
      species might be confused. 

PMID- 25991412
TI  - Laser Shock Peening on Zr-based Bulk Metallic Glass and Its Effect on Plasticity:
      Experiment and Modeling.
AB  - The Zr-based bulk metallic glasses (BMGs) are a new family of attractive
      materials with good glass-forming ability and excellent mechanical properties,
      such as high strength and good wear resistance, which make them candidates for
      structural and biomedical materials. Although the mechanical behavior of BMGs has
      been widely investigated, their deformation mechanisms are still poorly
      understood. In particular, their poor ductility significantly impedes their
      industrial application. In the present work, we show that the ductility of Zr
      based BMGs with nearly zero plasticity is improved by a laser shock peening
      technique. Moreover, we map the distribution of laser-induced residual stresses
      via the micro-slot cutting method, and then predict them using a three
      dimensional finite-element method coupled with a confined plasma model.
      Reasonable agreement is achieved between the experimental and modeling results.
      The analyses of serrated flows reveal plentiful and useful information of the
      underlying deformation process. Our work provides an easy and effective way to
      extend the ductility of intrinsically-brittle BMGs, opening up wider applications
      of these materials. 

PMID- 25991414
TI  - Evaluation Indexes of Military Hospitals From the Experts' Perspective: A
      Qualitative Study.
AB  - Given the importance of evaluation in an organization and considering the
      objectives and missions of military hospitals, we aimed to extract some indexes
      (in addition to common evaluation indexes) for use in evaluating military
      hospitals. This was an applied-type qualitative study. The participants were 15
      health experts who were first chosen by a purposeful sampling, which was then
      continued by theoretical sampling. The data obtained were analyzed by using
      MAXQDA11 software and the content analysis method. After 290 obtained codes were
      analyzed, 17 indexes in 6 domains were extracted, including capacity development
      for crisis periods, equipment and facilities, training and research, passive
      defense, treatment, and services, from which 8 indexes were related to capacity
      development for crisis periods and equipment and facilities (4 indexes each), 3
      indexes were related to services, and 6 indexes were related to training and
      research, passive defense, and treatment (2 indexes each). The results of the
      present research, as a supplement to current evaluation methods such as
      accreditation, can be used for the comprehensive evaluation of military
      hospitals.

PMID- 25991413
TI  - Relationship of contextual cueing and hippocampal volume in amnestic mild
      cognitive impairment patients and cognitively normal older adults.
AB  - There is currently some debate as to whether hippocampus mediates contextual
      cueing. In the present study, we examined contextual cueing in patients diagnosed
      with mild cognitive impairment (MCI) and healthy older adults, with the main goal
      of investigating the role of hippocampus in this form of learning. Amnestic MCI
      (aMCI) patients and healthy controls completed the contextual cueing task, in
      which they were asked to search for a target (a horizontal T) in an array of
      distractors (rotated L's). Unbeknownst to them, the spatial arrangement of
      elements on some displays was repeated thus making the configuration a contextual
      cue to the location of the target. In contrast, the configuration for novel
      displays was generated randomly on each trial. The difference in response times
      between repeated and novel configurations served as a measure of contextual
      learning. aMCI patients, as a group, were able to learn spatial contextual cues
      as well as healthy older adults. However, better learning on this task was
      associated with higher hippocampal volume, particularly in right hemisphere.
      Furthermore, contextual cueing performance was significantly associated with
      hippocampal volume, even after controlling for age and MCI status. These findings
      support the role of the hippocampus in learning of spatial contexts, and also
      suggest that the contextual cueing paradigm can be useful in detecting
      neuropathological changes associated with the hippocampus.

PMID- 25991415
TI  - Site-Specific Relationship Between Intracranial Aneurysm and Aortic Aneurysm.
AB  - BACKGROUND AND PURPOSE: The high prevalence of intracranial aneurysms (IAs) in
      patients with a bicuspid aortic valve or coarctation of the aorta suggests a link
      between IA and aortic pathology. However, studies reporting this link do not
      sufficiently address the heterogeneity of IAs arising from different anatomic
      locations. This study aimed to explore whether a location-specific relationship
      exists between the 2 kinds of aneurysms. METHODS: Retrospective institutional
      analysis of patients aged >=18 years with both IA and an aortic aneurysm (AA) was
      performed from 2005 to 2014. IAs were categorized based on their locations:
      internal carotid artery, other anterior circulation, and posterior arteries. AAs
      were classified as ascending, descending, infrarenal, or multiple. We analyzed
      the clinical characteristics and the distribution of IA in each AA group.
      RESULTS: Of 2375 patients, 660 with available intracranial angiography were
      screened for IA. We identified 71 patients with 97 IAs. The frequency of both
      anterior circulation-IAs and internal carotid artery-IAs differed significantly
      among the AA groups (P=0.001 and P=0.01, respectively). Anterior circulation-IAs
      were most frequently observed in ascending AA group and least frequently in
      infrarenal AA group. In contrast, internal carotid artery-IAs were found mostly
      in infrarenal AA group, least in ascending AA group. Proportions of patients
      having anterior circulation-IA and internal carotid artery-IA were also highest
      in ascending AA group and infrarenal AA group, respectively. The number of
      posterior arteries-IAs was too small to characterize. CONCLUSIONS: The differing
      distribution patterns of IA among AA groups suggest a site-specific sharing of
      pathomechanism between the 2 types of aneurysms.

PMID- 25991416
TI  - Soluble Epoxide Hydrolase in Hydrocephalus, Cerebral Edema, and Vascular
      Inflammation After Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Acute communicating hydrocephalus and cerebral edema are
      common and serious complications of subarachnoid hemorrhage (SAH), whose causes
      are poorly understood. Using a mouse model of SAH, we determined whether soluble
      epoxide hydrolase (sEH) gene deletion protects against SAH-induced hydrocephalus
      and edema by increasing levels of vasoprotective eicosanoids and suppressing
      vascular inflammation. METHODS: SAH was induced via endovascular puncture in wild
      type and sEH knockout mice. Hydrocephalus and tissue edema were assessed by T2
      weighted magnetic resonance imaging. Endothelial activation was assessed in vivo
      using T2*-weighted magnetic resonance imaging after intravenous administration of
      iron oxide particles linked to anti-vascular cell adhesion molecule-1 antibody 24
      hours after SAH. Behavioral outcome was assessed at 96 hours after SAH with the
      open field and accelerated rotarod tests. RESULTS: SAH induced an acute sustained
      communicating hydrocephalus within 6 hours of endovascular puncture in both wild
      type and sEH knockout mice. This was followed by tissue edema, which peaked at 24
      hours after SAH and was limited to white matter fiber tracts. sEH knockout mice
      had reduced edema, less vascular cell adhesion molecule-1 uptake, and improved
      outcome compared with wild-type mice. CONCLUSIONS: Genetic deletion of sEH
      reduces vascular inflammation and edema and improves outcome after SAH. sEH
      inhibition may serve as a novel therapy for SAH.

PMID- 25991418
TI  - Costs of caring for children with an intellectual developmental disorder.
AB  - BACKGROUND: Caring for a child with intellectual developmental disorder (IDD) is
      expensive for the medical system, for the family, and for society in general.
      Whereas the health care costs of IDD have been described, the societal and
      parental costs of IDD have been less well documented. OBJECTIVE: Our goal was to
      estimate the out-of-pocket costs to parents, and the non-health system costs to
      society, of raising a child with IDD. METHODS: We used an online retrospective
      survey, previously developed by our group, to collect parental and societal costs
      to families of 80 children who presented with IDD of unknown etiology in British
      Columbia, Canada. RESULTS: Median annual parental costs of caring for 80 children
      with IDD was CAD$44,570 (range CAD$2245-$225,777). The largest contributors to
      parental costs were income loss and caregiving time costs. Median annual societal
      costs (excluding health system costs) were CAD$27,428 (range CAD$0-$119,188). In
      school age children, the largest contributor to societal costs was a per child
      school subsidy. Both parental and societal costs increased with increasing IDD
      severity. Parental costs were not adequately compensated by government benefits
      received. CONCLUSIONS: Although medical care is universally available through
      Canadian provincial health systems and social assistance is provided to the
      families of children with IDD, parents continue to bear a substantial financial
      burden beyond that associated with raising an unaffected child.

PMID- 25991417
TI  - Hemodynamic Characteristics of Cerebral Arteriovenous Malformation Feeder Vessels
      With and Without Aneurysms.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of aneurysms associated with cerebral
      arteriovenous malformation (AVM) feeder vessels is poorly understood. We sought
      to determine the hemodynamic characteristics of AVM feeder vessels with and
      without aneurysms. METHODS: Patients with AVMs associated with feeder aneurysms
      who had flow, vessel diameter, and wall shear stress measured before treatment
      using quantitative magnetic resonance angiography were retrospectively reviewed.
      Feeders within each AVM were classified into 2 groups based on presence or
      absence of aneurysms. Hemodynamic parameters were calculated for each arterial
      feeder and then compared between the 2 groups. RESULTS: Eleven patients had AVMs
      with feeder aneurysms. Of 35 total feeder arteries, 12 had an aneurysm and 23
      feeders did not have any aneurysms. Absolute mean flow was higher (510.2 versus
      438.4 mL/min; P=0.53) and vessel diameter was lower (4.0 versus 4.8 mm; P=0.24)
      in feeders with aneurysms but not significantly. However, wall shear stress (96.2
      versus 28.0 dynes/cm2; P=0.04) was significantly higher in feeders with
      aneurysms. CONCLUSIONS: Wall shear stress is significantly higher among cerebral
      AVM feeders harboring aneurysms. Despite similarly high flows, feeder artery
      diameter tended to be smaller if an aneurysm was present, suggesting that AVM
      feeders with aneurysms are a subgroup in which vessel remodeling cannot
      compensate for increased blood flow.

PMID- 25991419
TI  - Work-related measures of physical and behavioral health function: Test-retest
      reliability.
AB  - BACKGROUND: The Work Disability Functional Assessment Battery (WD-FAB), developed
      for potential use by the US Social Security Administration to assess work-related
      function, currently consists of five multi-item scales assessing physical
      function and four multi-item scales assessing behavioral health function; the WD
      FAB scales are administered as Computerized Adaptive Tests (CATs). OBJECTIVE: The
      goal of this study was to evaluate the test-retest reliability of the WD-FAB
      Physical Function and Behavioral Health CATs. METHODS: We administered the WD-FAB
      scales twice, 7-10 days apart, to a sample of 376 working age adults and 316
      adults with work-disability. Intraclass correlation coefficients were calculated
      to measure the consistency of the scores between the two administrations.
      Standard error of measurement (SEM) and minimal detectable change (MDC90) were
      also calculated to measure the scales precision and sensitivity. RESULTS: For the
      Physical Function CAT scales, the ICCs ranged from 0.76 to 0.89 in the working
      age adult sample, and 0.77-0.86 in the sample of adults with work-disability.
      ICCs for the Behavioral Health CAT scales ranged from 0.66 to 0.70 in the working
      age adult sample, and 0.77-0.80 in the adults with work-disability. The SEM
      ranged from 3.25 to 4.55 for the Physical Function scales and 5.27-6.97 for the
      Behavioral Health function scales. For all scales in both samples, the MDC90
      ranged from 7.58 to 16.27. CONCLUSION: Both the Physical Function and Behavioral
      Health CATs of the WD-FAB demonstrated good test-retest reliability in adults
      with work-disability and general adult samples, a critical requirement for
      assessing work related functioning in disability applicants and in other
      contexts.

PMID- 25991420
TI  - Serial type-specific human papillomavirus (HPV) load measurement allows
      differentiation between regressing cervical lesions and serial virion productive
      transient infections.
AB  - Persistent high-risk human papillomavirus (HPV) infection is strongly associated
      with the development of high-grade cervical intraepithelial neoplasia (CIN) or
      cancer. Not all persistent infections lead to cancer. Viral load measured at a
      single time-point is a poor predictor of the natural history of HPV infections.
      However the profile of viral load evolution over time could distinguish
      nonprogressive from progressive (carcinogenic) infections. A retrospective
      natural history study was set up using a Belgian laboratory database including
      more than 800,000 liquid cytology specimens. All samples were submitted to qPCR
      identifying E6/E7 genes of 18 HPV types. Viral load changes over time were
      assessed by the linear regression slope. Database search identified 261 untreated
      women with persistent type-specific HPV DNA detected (270 infections) in at least
      three of the last smears for a average period of 3.2 years. Using the coefficient
      of determination (R2) infections could be subdivided in a latency group (n = 143;
      R2 < 0.85) and a regressing group (n = 127; R2 >= 0.85). In (>= 3) serial viral
      load measurements, serial transient infections with latency is characterized by a
      nonlinear limited difference in decrease or increase of type-specific viral load
      (R2 < 0.85 and slopes between 2 measurements 0.0010 and -0.0010 HPV copies/cell
      per day) over a longer period of time (1553 days), whereas regression of a clonal
      cell population is characterized by a linear (R2 >= 0.85) decrease (-0.0033 HPV
      copies/cell per day) over a shorter period of time (708 days; P < 0.001). Using
      serial HPV type-specific viral load measurements we could for the first time
      identify regressing CIN2 and CIN3 lesions. Evolution of the viral load is an
      objective measurable indicator of the natural history of HPV infections and could
      be used for future triage in HPV-based cervical screening programs.

PMID- 25991421
TI  - Interleukin-6 and C-reactive protein load in pre-storage and post-storage white
      blood cell-filtered red blood cell transfusions in premature infants.
AB  - OBJECTIVE: Leukocyte contamination during blood transfusion can cause many
      adverse effects. Filtration can be performed either at bedside during the
      transfusion or as pre-storage filtration. Pre-storage filtration is superior to
      bedside filtration because leukocytes are removed prior to storage, thus
      preventing further adverse effects associated with the storage of these cells.
      METHODS AND MATERIALS: One hundred and six infants were randomised into two
      groups: pre-storage filtration (group 1, n = 53) and bedside filtration (group 2,
      n = 53). C-reactive protein (CRP) and interleukin-6 (IL-6) levels were analysed
      within 24 h prior to the transfusion and 24 h after completion of the
      transfusion. RESULTS: In group 1, pre-transfusion median CRP and IL-6 levels were
      2.95 (0.73-10.25) mg L(-1) and 8.59 (3.45-20.55) pg L(-1) , respectively, and
      post-transfusion median CRP and IL-6 levels were 2.28 (0.44-12.87) mg L(-1) and
      6.62 (2.18-27.87) pg L(-1) , respectively. In group 2, pre-transfusion median CRP
      and IL-6 levels were 1.30 (0.40-7.84) mg L(-1) and 4.40 (2-17.12) pg L(-1) ,
      respectively, and post-transfusion median CRP and IL-6 levels were 3.50 (0.50
      7.85) mg L(-1) and 8.30 (3.48-23.75) pg L(-1) , respectively. There were no
      differences between pre-storage and post-storage leukoreduction average IL-6 and
      CRP levels in either group (P > 0.05 for both). Packed red blood cell (PRBC)
      related necrotizing enterocolitis was detected in one infant in group 2.
      CONCLUSIONS: Because leukocytes in PRBC transfusions can be associated with many
      undesirable effects, leukoreduction is the best choice to prevent those effects.
      However, this method is still controversial. We demonstrated that using pre
      storage and post-storage leukoreduction methods in erythrocyte transfusions did
      not change CRP or IL-6 levels, which are indicators of acute-phase response.

PMID- 25991422
TI  - Complications and Mortality in Patients Undergoing Transcatheter Aortic Valve
      Replacement With Edwards SAPIEN & SAPIEN XT Valves: A Meta-Analysis of World-Wide
      Studies and Registries Comparing the Transapical and Transfemoral Accesses.
AB  - INTRODUCTION: Both transfemoral (TF) and transapical (TA) routes are utilized for
      Transcatheter Aortic Valve Replacement (TAVR) using Edwards SAPIEN & SAPIEN XT
      valves. We intended to perform a meta-analysis comparing the complication rates
      between these two approaches in studies published before and after the
      standardized Valve Academic Research Consortium (VARC) definitions. METHODS: We
      performed a comprehensive electronic database search for studies published until
      January 2014 comparing TF and TA approaches using the Edwards SAPIEN/SAPIEN XT
      aortic valve. Studies were analyzed based on the following endpoints: 1-year
      mortality, 30-day mortality, stroke, new pacemaker implantation, bleeding, and
      acute kidney injury. RESULTS: Seventeen studies were included in the meta
      analysis. Patients undergoing TA TAVR had a significantly higher logistic
      EuroSCORE (24.6 +/- 12.9 vs. 21.3 +/- 12.0; P < 0.001). The cumulative risks for
      30-day mortality (RR 0.61; 95%CI 0.46-0.81; P = 0.001), 1-year mortality (RR
      0.68; 95%CI 0.55-0.84; P < 0.001), and acute kidney injury (RR 0.53; 95%CI 0.38
      0.73; P < 0.001) were significantly lower for patients undergoing TF as compared
      to TA approach. Both approaches had a similar incidence of 30-day stroke,
      pacemaker implantation, and major or life-threatening bleeding. Studies utilizing
      the VARC definitions and those pre-dating VARC yielded similar results.
      CONCLUSION: This meta-analysis demonstrates a decreased 30-day and 1-year
      mortality in TF TAVR as compared to TA TAVR. Post-procedure acute kidney injury
      and the need for renal replacement therapy are also significantly lower in the TF
      group. These differences hold true even after utilizing the standardized Valve
      Academic Research Consortium criteria.

PMID- 25991423
TI  - Signal intensity of superficial white matter on phase difference enhanced imaging
      as a landmark of the perirolandic cortex.
AB  - Background The superficial white matter (SWM), which fills the space between the
      deep white matter and the cortex, has not been well characterized. Purpose To
      determine whether the assessment of the relative signal intensity (SI) of the SWM
      in the precentral and postcentral gyri on phase difference enhanced (PADRE)
      images contributes in establishing anatomical landmark. Material and Methods The
      study population consisted of 43 normal subjects (28 women, 15 men; mean age,
      52.9 years; age range, 22-90 years). By the consensus of two observers, the
      precentral gyri, postcentral gyri, and superior frontal cortex (SFC) were
      identified based on the established anatomical methods. The SI of the SWM in the
      precentral and postcentral gyri on PADRE images was divided into three grades in
      comparison with that of the SFC: Grade I, isointense; Grade II, slightly
      hypointense; and Grade III, markedly hypointense. Results The SWM in the
      precentral and postcentral gyri showed hypointensity on PADRE images. In the SI
      analyses of the PADRE images, the Grade I, Grade II, and Grade III appearances
      were found in one (1%), 20 (23%), and 65 (76%) of the 86 precentral gyri (43
      subjects), respectively, and in one (1%), 23 (27%), and 62 (72%) of the 86
      postcentral gyri, respectively. Conclusion On PADRE images, the perirolandic SWM
      showed hypointensity compared to other cerebral cortices, which probably reflects
      differences in the concentrations of the nerve fibers, as well as the higher
      myelin content. PADRE may be useful for the identification of the central sulcus
      by assessing the SI of the SWM.

PMID- 25991424
TI  - Indole Derivatives as Anticancer Agents for Breast Cancer Therapy: A Review.
AB  - Breast cancer (BC) is the second most common cause of cancer-related deaths in
      women throughout the world. Multiple drugs have been approved by US-FDA for
      breast related malignancies. Frequent emergence of resistances creates the severe
      need of newer moieties that are free from such problems. Drugs targeting breast
      cancer have been observed to be based on the multiple mechanisms of action, and
      various indole based anticancer agents have also been explored. Moreover, indoles
      have promising anti-cancer potential; there has been the emphasis on the
      synthesis of indole derivatives to overcome problems faced by existing
      therapeutic agents. Taking into consideration the above-mentioned facts we have
      analyzed in detail the possible role of indole based anticancer agents typically
      for breast related malignancies. This is the first exhaustive review that jointly
      covers various synthetic anticancer indole derivatives and related signaling
      pathways by which these derivatives have shown promising anti-breast cancer
      potential. 

PMID- 25991425
TI  - Exploring Cancer Therapeutics with Natural Products from African Medicinal
      Plants, Part II: Alkaloids, Terpenoids and Flavonoids.
AB  - Cancer stands as second most common cause of disease-related deaths in humans.
      Resistance of cancer to chemotherapy remains challenging to both scientists and
      physicians. Medicinal plants are known to contribute significantly to a large
      population of Africa, which is to a very large extent linked to folkloric claims
      which is part of their livelihood. In this review paper, the potential of
      naturally occurring anti-cancer agents from African flora has been explored, with
      suggested modes of action, where such data is available. Literature search
      revealed plant-derived compounds from African flora showing anti-cancer and/or
      cytotoxic activities, which have been tested in vitro and in vivo. This
      corresponds to 400 compounds (from mildly active to very active) covering various
      compound classes. However, in this part II, we only discussed the three major
      compound classes which are: flavonoids, alkaloids and terpenoids. 

PMID- 25991426
TI  - Recent Advances in Phenanthroindolizidine and Phenanthroquinolizidine Derivatives
      with Anticancer Activities.
AB  - Phenanthroindolizidine and phenanthroquinolizidine derivatives constitute a
      series of compounds that are being intensively studied as potential anticancer
      agents. Related natural products such as antofine and tylophorine alkaloids are
      well known for their high cytotoxic activity; however, their clinical application
      has been limited because of their side effects. In this review we report, in
      detail, on the main structural modifications applied to the
      phenanthroindolizidine and phenanthroquinolizidine skeletons, and we also
      describe their associated anticancer activities. New derivatives with promising
      antitumoral activities have emerged. Simplified analogues were prepared using
      rapid synthetic routes, and a certain number of these analogues displayed
      increased anticancer activity and selectivity towards tumor cell lines. It is
      hoped that a better understanding of the mechanisms of action associated with
      structure-activity relationships (SAR) will enable us to rationalize the
      development of new anticancer drugs. 

PMID- 25991427
TI  - Synthesis and characterization of a new retinoic acid ECPIRM as potential
      chemotherapeutic agent for human cutaneous squamous carcinoma.
AB  - Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers
      worldwide, requiring effective therapeutic interventions. Retinoids are important
      chemopreventive and therapeutic agents for a variety of human cancers including
      CSCC. In this study we synthesized a novel retinoic derivative N-(4
      ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological
      activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM
      had better inhibitory effect on the proliferation of squamous carcinoma cells SCL
      1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid.
      ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically,
      ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of
      CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In
      addition, these effects were at least partially due to the inhibition of JNK/ ERK
      AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are
      independent of the classical retinoid receptor pathway, suggesting that the novel
      compound will have less side-effects in chemotherapy. These findings demonstrate
      that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential
      therapeutic agent against CSCC. 

PMID- 25991428
TI  - Design, Synthesis, and Evaluation of Genistein Analogues as Anti-Cancer Agents.
AB  - Genistein is a bioactive isoflavone derived from soybeans. The tie-in between the
      intake of genistein and the decreased incidence of some solid tumors (including
      prostate cancer) has been demonstrated by epidemiological studies. The potential
      of genistein in treating prostate cancer has also been displayed by in vitro cell
      based and in vivo animal experiments. Genistein has entered clinical trials for
      both chemoprevention and potential treatment of prostate cancer. Even though the
      low oral bioavailability has presented the major challenges to genistein's
      further clinical development, chemical modulation of genistein holds the promise
      to generate potential anti-prostate cancer agents with enhanced potency and/or
      better pharmacokinetic profiles than genistein. As part of our ongoing project to
      develop natural products-based anti-prostate cancer agents, the current study was
      undertaken to synthesize eight genistein analogues for cytotoxic evaluation in
      three prostate cancer cell lines (PC-3, DU-145, LNCaP; both androgen-sensitive
      and androgen-refractory cell lines), as well as one aggressive cervical cancer
      cell line (HeLa). Eight genistein analogues have been successfully synthesized
      with Suzuki-Miyaura coupling reaction as a key step. Their in vitro anti-cancer
      potential was evaluated by trypan blue exclusion assay and WST-1 cell
      proliferation assay against a panel of four human cancer cell lines. The acquired
      data suggest i) that the C-5 and C-7 hydroxyl groups in genistein are very
      important for the cytotoxicity and anti-proliferative activity; and ii) that 1
      alkyl-1H-pyrazol-4-yl and pyridine-3-yl might act as good bioisosteres for the 4'
      hydroxyphenyl moiety in genistein. 

PMID- 25991429
TI  - New oral anticoagulants: dosing and monitoring.

PMID- 25991430
TI  - Teaching in the clinical workplace: looking beyond the power of 'the one'.

PMID- 25991432
TI  - The role of surface oxygenated-species and adsorbed hydrogen in the oxygen
      reduction reaction (ORR) mechanism and product selectivity on Pd-based catalysts
      in acid media.
AB  - Oxygen reduction reaction (ORR) is investigated on bulk PdO-based catalysts
      (oxides of Pd and Pd3Co) in oxygen-saturated 0.1 M HClO4 to establish the role of
      surface oxides and adsorbed hydrogen in the activity and product selectivity
      (H2O/H2O2). The initial voltammetric features suggest that the oxides are
      inactive toward ORR. The evolution of the ORR voltammograms and potential
      dependent H2O2 generation features on the PdO catalyst suggest gradual and
      parallel in situ reduction of the bulk PdO phase below ~0.4 V in the hydrogen
      underpotential deposition (Hupd) region; the reduction of the bulk PdO catalyst
      is confirmed from the X-ray photoelectron spectra (XPS) and X-ray diffraction
      (XRD) patterns. The potential-dependent H2O2 generation features originate due to
      the presence of surface oxides and adsorbed hydrogen; this is further confirmed
      using halide ions (Cl(-) and Br(-)) and peroxide as the external impurities. 

PMID- 25991431
TI  - Quinolyl analogues of norlobelane: novel potent inhibitors of
      [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine uptake at the vesicular
      monoamine transporter-2.
AB  - We have previously shown that quinolyl moieties are attractive structural
      replacements for the phenyl groups in lobelane. These quinolyl analogues had
      improved water-solubility over lobelane and retained the potent vesicular
      monoamine transporter-2 (VMAT-2) inhibitory properties of the parent compound,
      with quinlobelane (4) exhibiting potent inhibition of uptake at VMAT-2 (Ki=51nM).
      However, the VMAT-2 inhibitory properties of quinolyl analogues of norlobelane,
      which is equipotent with lobeline as an inhibitor of [(3)H]dopamine (DA) uptake
      at VMAT-2, have not been reported. In the current communication, we describe the
      synthesis of some novel des-methyl quinolyl analogues of lobelane that exhibit
      greater affinity (Ki=178-647nM) for the dihydrotetrabenazine binding site located
      on VMAT-2 compared with lobelane (Ki=970nM), norlobelane (Ki=2310nM) and
      quinlobelane (Ki=2640nM). The most potent compounds, 14 and 15, also exhibited
      inhibition of [(3)H]DA uptake at VMAT-2 (Ki=42nM) which was comparable to both
      lobelane (Ki=45nM) and norlobelane (Ki=43nM). Results reveal that binding
      affinity at VMAT-2 serves as an accurate predictor of inhibition of the function
      of VMAT-2 for the majority of these analogues. These novel analogues are under
      consideration for further development as treatments for methamphetamine abuse. 

PMID- 25991433
TI  - c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).
AB  - INTRODUCTION: c-Jun N-terminal kinases (JNKs) are involved in the emergence and
      progression of diverse pathologies such as neurodegenerative, cardiovascular and
      metabolic disorders as well as inflammation and cancer. In recent years, several
      highly selective pan-JNK inhibitors have been characterized and three chemical
      entities targeting JNKs have been investigated in clinical trials. AREAS COVERED:
      This review summarizes patents claiming inhibitors of all JNK isoforms published
      between 2010 and 2014. Although primarily focusing on the patent literature,
      relevant peer-reviewed publications related to the covered patents have also been
      included. Moreover, key patents claiming novel applications of previously
      published chemical entities are reviewed. The article highlights a total of 28
      patents from nine pharmaceutical companies and academic research groups. EXPERT
      OPINION: Although some selective pan-JNK inhibitors with reasonable in vivo
      profiles are now available, little is known about the isoform selectivity
      required for each particular indication and the development of isoform-selective
      JNK inhibitors still represents a challenge in JNK drug discovery. Moreover,
      isoform-selective tool compounds are a prerequisite to a comprehensive
      understanding of the biology of each JNK isoform. Potential approaches towards
      such compounds include the design of type-II and type-I(1)/2 binders, which are
      absent in the current JNK inhibitor portfolios, as well as the design of novel
      allosteric inhibitors. Furthermore, covalent inhibition, which already led to the
      first high-quality probe for JNKs, might be further exploited for gaining
      selectivity and in vivo efficacy. With regard to a potential therapeutic
      application, the recently proposed concept of covalent reversible inhibitors is
      expected to be attractive.

PMID- 25991434
TI  - Does Tranexamic Acid Reduce Blood Loss and Transfusion Requirements Associated
      With the Periacetabular Osteotomy?
AB  - BACKGROUND: Tranexamic acid (TXA) has shown safety and efficacy in reducing blood
      loss associated with various surgical procedures. However, to our knowledge there
      are no studies evaluating the effect of TXA on blood loss and transfusion
      requirements associated with periacetabular osteotomy (PAO). QUESTIONS/PURPOSES:
      The main purpose of this study is to determine whether TXA reduces blood loss and
      transfusion use in patients undergoing PAO for symptomatic acetabular dysplasia.
      Our secondary purpose was to compare the frequency of symptomatic thromboembolic
      events between patients undergoing surgery with and without TXA. METHODS: A
      consecutive series of 100 periacetabular osteotomies performed by one surgeon was
      reviewed to compare the groups immediately before and after implementation of
      routine use of tranexamic acid (two retrospective cohorts). TXA dosing followed
      an established protocol with a standard dose of 1 g infused intravenously during
      10 minutes before skin incision and an additional 1 g intravenously at wound
      closure. Outcome measures include total estimated blood loss perioperatively and
      transfusion requirements. Total estimated blood loss was calculated using a
      formula built from the National Surgical Quality Improvement Program data
      regarding surgical blood loss. RESULTS: The mean perioperative total estimated
      blood loss was less in the patients receiving TXA compared with blood loss in
      patients who did not receive TXA (706 mL versus 1021 mL; p<0.001; 95% CI, -495 to
      -134). Twenty-six (52%) of the 50 patients who did not receive TXA had
      postoperative blood transfusions compared with 15 (30%) of 50 who received TXA
      (odds ratio, 0.395; 95% CI, 0.174-0.899; p=0.0414). No symptomatic deep vein
      thromboses or symptomatic pulmonary emboli were identified in either group.
      CONCLUSIONS: TXA reduces estimated blood loss and the frequency of transfusions
      in patients undergoing PAO for treatment of symptomatic acetabular dysplasia.
      Future prospective studies should confirm our findings to determine whether
      patients undergoing PAO should receive routine perioperative TXA. LEVEL OF
      EVIDENCE: Level III, therapeutic study.

PMID- 25991435
TI  - What Are the Risk Factors and Management Options for Infection After
      Reconstruction With Massive Bone Allografts?
AB  - BACKGROUND: Massive bone allografts have been used for limb salvage of bone tumor
      resections as an alternative to endoprosthesis, although they have different
      outcomes and risks. The use of massive bone allografts has been thought to be
      associated with a high risk for infection, and there is no general consensus on
      the management of this complication and final outcome. Because infection is such
      a devastating complication of limb salvage, at times leading to loss of a limb,
      recognizing the risk factors for infection and the results of treatment is
      important. QUESTIONS/PURPOSES: The purposes of this study were (1) to analyze the
      frequency of infection in a group of patients treated with massive bone
      allografts; (2) to analyze risk factors such as age, sex, affected bone, type of
      reconstruction, operative room used, primary or revision procedure, length of
      postoperative antibiotic administration, and use of chemotherapy; and (3) to
      determine the likelihood that treatment of an infected allograft will result in a
      successful reconstruction. METHODS: We retrospectively analyzed the records of
      patients treated with massive bone allografts for a benign or malignant bone
      tumor or as a revision for a previous limb salvage procedure between 1985 and
      2011. During this period, 673 patients were reconstructed with massive bone
      allografts in long bones, which included 272 osteoarticular, 246 intercalary, and
      155 allograft-prosthetic composite reconstructions. Using a chart review, we
      ascertained the frequency of infection and reoperations after the treatment of
      infected allografts. Minimum followup was 2 years unless death occurred earlier
      (mean, 106 months; range, 6-360 months), and no patient was lost to followup. The
      selected variables were analyzed using multivariate logistic regression to
      identify risk factors for infection. We analyzed survivorship free of infection
      as the endpoint. RESULTS: During followup, 60 patients (9%) had a bacterial
      infection of the allograft with a survivorship free from infection of 92% at 5
      years (95% confidence interval [CI], 90%-94%) and 91% at 10 years (95% CI, 89%
      93%). We found that tibia allografts (p < 0.001; odds ratio [OR], 3.17; 95% CI,
      1.80-5.60), male patients (p < 0.029; OR, 1.92; 95% CI, 1.08-3.49), procedures
      performed in a conventional operating room (p < 0.002; OR, 3.15; 95% CI, 1.58
      6.62), and the use of longer periods of postoperative antibiotics (p < 0.041; OR,
      2.25; 95% CI, 1.02-4.88) were patient factors associated with a greater risk of
      infection. In 11 patients (18%, 11 of 60 infections) the infection was controlled
      with antibiotics and surgical debridement; however, in 49 patients (82%, 49 of 60
      infections), this approach failed, so the allograft was removed and a temporary
      cement spacer with antibiotic was implanted to control the infection. Forty-one
      patients subsequently had the spacer removed and were reconstructed after
      infection control with another bone allograft in 24 and an endoprostheses in 17.
      Four patients underwent an amputation for infection and four died of disease with
      the spacer in place. When we analyzed the 41 patients with a second
      reconstruction, 14 failed with a new infection (34%, 14 of 41 secondary
      reconstructed) of whom 12 had been reconstructed with bone allograft (29%) and
      two had endoprostheses (5%). CONCLUSIONS: Management of infections of massive
      bone allografts with antibiotics and surgical debridement usually resulted in
      failure. Infections could be treated with resection of the allograft,
      antibiotics, a temporary cement spacer with antibiotics, and a repeat
      reconstruction; however, this approach is unlikely to be successful if a second
      bone allograft is used. Infections are difficult to treat, and more studies are
      needed, but we propose that it might be preferable to use endoprosthesis
      reconstruction for salvage of an infected allograft. LEVEL OF EVIDENCE: Level
      III, therapeutic study.

PMID- 25991436
TI  - Editorial: Why Some Authors Make Bad Choices--Peer Review for Hire and Other Sad
      Stories.

PMID- 25991437
TI  - Harry Smith, FRS: co-founding editor and first Chief Editor of Plant, Cell &
      Environment.

PMID- 25991438
TI  - Promotion of Wound Healing by an Agonist of Adenosine A2A Receptor Is Dependent
      on Tissue Plasminogen Activator.
AB  - Impaired wound healing, as it occurs in diabetes mellitus or long-term corticoid
      treatment, is commonly associated with disability, diminished quality of life,
      and high economic costs. Selective agonists of the A2A receptor subtype of
      adenosine, an endogenous regulator of inflammation, promote tissue repair in
      animal models, both healthy and with impaired healing. Plasmin-mediated
      proteolysis of fibrin and other matrix proteins is essential for cell migration
      at sites of injury. Since adenosine A2A receptor activation increases plasminogen
      activator release from macrophages and mast cells, we studied the effect of a
      selective agonist, CGS-21680, on full-thickness excisional wound closure in wild
      type, urokinase plasminogen activator (uPA)-deficient, and tissue plasminogen
      activator (tPA)-deficient mice. Wound closure was impaired in tPA- and uPA
      deficient mice as compared with wild-type mice, and topical application of CGS
      21680 significantly increased the rate at which wounds closed in wild-type mice
      and uPA-deficient mice, but not in tPA-deficient mice. Immunostaining of tissue
      sections showed that tPA was present in endothelial cells and histiocytes by day
      3 post-wound and also by day 6. In contrast, uPA was more prominent in these cell
      types only by day 6 post-wound. Our results confirm that plasminogen activation
      contributes to wound repair and are consistent with the hypothesis that adenosine
      A2A receptor activation promotes wound closure by a mechanism that depends upon
      tPA, but not uPA. Moreover, our results suggest that topical adenosine A2A
      receptor agonists may be useful in promotion of wound closure in patients with
      impaired wound healing. 

PMID- 25991439
TI  - Developing and validating a high-throughput assay for salinity tissue tolerance
      in wheat and barley.
AB  - MAIN CONCLUSION: Leaf tissue tolerance was strongly and positively correlated
      with overall salt tolerance in barley, but not in wheat where the inability of
      sensitive varieties to exclude Na(+) is compensated by their better ability to
      handle Na(+) accumulated in the shoot via tissue tolerance mechanisms. A new high
      throughput assay was developed to use the excised leaves to eliminate the
      confounding contribution of sodium exclusion mechanisms and evaluate genetic
      variability in salinity tissue tolerance in a large number of wheat (Triticum
      aestivum and Triticum turgidum ssp. durum) and barley (Hordeum vulgare)
      accessions. The changes in relative chlorophyll content (measured as chlorophyll
      content index, CCI) in excised leaves exposed to 50 mM NaCl for 48 h were found
      to be a reliable indicator of leaf tissue tolerance. In both wheat and barley,
      relative CCI correlated strongly with the overall plant salinity tolerance
      (evaluated in glasshouse experiments). To a large extent, this tissue tolerance
      was related to more efficient vacuolar Na(+) sequestration in leaf mesophyll, as
      revealed by fluorescent Na(+) dye imaging experiments. However, while in barley
      this correlation was positive, tissue tolerance in wheat correlated negatively
      with overall salinity tolerance. As a result, more salt-sensitive durum wheat
      genotypes possessed higher tissue tolerance than bread wheat plants, and this
      negative correlation was present within each of bread and durum wheat clusters as
      well. Overall, these results indicate that the lack of effective Na(+) exclusion
      ability in sensitive wheat varieties is compensated by their better ability to
      handle Na(+) accumulated in the shoot via tissue tolerance mechanisms.
      Implications of these findings for plant breeding for salinity tolerance are
      discussed.

PMID- 25991440
TI  - Neural circuits: Pain or pleasure?

PMID- 25991441
TI  - Neuronal circuits for fear and anxiety.
AB  - Decades of research has identified the brain areas that are involved in fear,
      fear extinction, anxiety and related defensive behaviours. Newly developed
      genetic and viral tools, optogenetics and advanced in vivo imaging techniques
      have now made it possible to characterize the activity, connectivity and function
      of specific cell types within complex neuronal circuits. Recent findings that
      have been made using these tools and techniques have provided mechanistic
      insights into the exquisite organization of the circuitry underlying internal
      defensive states. This Review focuses on studies that have used circuit-based
      approaches to gain a more detailed, and also more comprehensive and integrated,
      view on how the brain governs fear and anxiety and how it orchestrates adaptive
      defensive behaviours. 

PMID- 25991442
TI  - Compromised autophagy and neurodegenerative diseases.
AB  - Most neurodegenerative diseases that afflict humans are associated with the
      intracytoplasmic deposition of aggregate-prone proteins in neurons and with
      mitochondrial dysfunction. Autophagy is a powerful process for removing such
      proteins and for maintaining mitochondrial homeostasis. Over recent years,
      evidence has accumulated to demonstrate that upregulation of autophagy may
      protect against neurodegeneration. However, autophagy dysfunction has also been
      implicated in the pathogenesis of various diseases. This Review summarizes the
      progress that has been made in our understanding of how perturbations in
      autophagy are linked with neurodegenerative diseases and the potential
      therapeutic strategies resulting from the modulation of this process. 

PMID- 25991443
TI  - Immune attack: the role of inflammation in Alzheimer disease.
AB  - The past two decades of research into the pathogenesis of Alzheimer disease (AD)
      have been driven largely by the amyloid hypothesis; the neuroinflammation that is
      associated with AD has been assumed to be merely a response to pathophysiological
      events. However, new data from preclinical and clinical studies have established
      that immune system-mediated actions in fact contribute to and drive AD
      pathogenesis. These insights have suggested both novel and well-defined potential
      therapeutic targets for AD, including microglia and several cytokines. In
      addition, as inflammation in AD primarily concerns the innate immune system -
      unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and
      encephalitides - the concept of neuroinflammation in AD may need refinement. 

PMID- 25991444
TI  - A search strategy to identify studies on the prognosis of work disability: a
      diagnostic test framework.
AB  - OBJECTIVE: Searching the medical literature for evidence on prognosis is an
      important aspect of evidence-based disability evaluation. To facilitate this, we
      aimed to develop and evaluate a comprehensive and efficient search strategy in
      PubMed, to be used by either researchers or practitioners and that will identify
      articles on the prognosis of work disability. METHODS: We used a diagnostic test
      analytic framework. First, we created a reference set of 225 articles on the
      prognosis of work disability by screening a total of 65,692 titles and abstracts
      from10 journals in the period 2000-2009. Included studies had a minimum follow-up
      of 6 months, participants in the age of 18-64 with a minimum sick leave of 4
      weeks or longer or having serious activity limitations in 50% of the cases and
      outcome measures that reflect impairments, activity limitations or participation
      restrictions. Using text mining methods, we extracted search terms from the
      reference set and, according to sensitivity and relative frequency, we combined
      these into search strings. RESULTS: Both the research and the practice search
      filter outperformed existing filters in occupational health, all combined with
      the Yale-prognostic filter. The Work Disability Prognosis filter for Research
      showed a comprehensiveness of 90% (95% CI 86 to 94) and efficiency expressed more
      user-friendly as Number Needed to Read=20 (95% CI 17 to 34). CONCLUSIONS: The
      Work Disability Prognosis filter will help practitioners and researchers who want
      to find prognostic evidence in the area of work disability evaluation. However,
      further refining of this filter is possible and needed, especially for the
      practitioner for whom efficiency is especially important.

PMID- 25991445
TI  - Do parental education and income matter? A nationwide register-based study on HPV
      vaccine uptake in the school-based immunisation programme in Norway.
AB  - OBJECTIVE: Vaccine against human papillomavirus (HPV) has been offered free of
      charge to all 12-year-old girls in Norway since 2009. Nevertheless, the uptake of
      HPV vaccine is lower than for other childhood vaccines. The aim of this study was
      to examine whether parental education and income are associated with initiation
      and completion of HPV vaccination. DESIGN: Nationwide register-based study.
      SETTING: Publicly funded childhood immunisation programme in Norway.
      PARTICIPANTS: 91,405 girls born between 1997 and 1999 and registered in the
      Norwegian Central Population Registry were offered HPV vaccine during the first 3
      programme years. Of these, 84,139 had complete information on all variables and
      were included in the study. MEASUREMENTS: Information on HPV-vaccination status
      was obtained from the Norwegian Immunisation Registry. Data on socioeconomic
      factors were extracted from Statistics Norway. Risk differences (RDs) and CIs
      were estimated with Poisson regression. RESULTS: In the study sample, 78.3%
      received at least one dose of HPV vaccine and 73.6% received all three doses.
      High maternal education was significantly associated with lower probability of
      initiating HPV vaccination (multivariable RD=-5.5% (95% CI -7.0% to -4.0%) for
      highest compared with lowest education level). In contrast, high maternal income
      was significantly associated with higher probability of initiating vaccination
      (multivariable RD=10.1% (95% CI 9.0% to 11.3%) for highest compared with lowest
      quintile). Paternal education and income showed similar, but weaker,
      associations. The negative association between education and initiation was only
      seen for incomes below the median value. CONCLUSIONS: In spite of the presumably
      equal access to HPV vaccine in Norway, we found socioeconomic disparities in
      vaccine uptake. More studies are needed to explain the underlying factors
      responsible for the observed socioeconomic differences. Insight into these
      factors is necessary to target information and increase vaccination coverage to
      ultimately reduce HPV-related disease across socioeconomic barriers.

PMID- 25991446
TI  - Effectiveness of moxibustion for allergic rhinitis: protocol for a systematic
      review.
AB  - INTRODUCTION: The objective of this review is to systematically evaluate the
      effectiveness of moxibustion for treating allergic rhinitis (AR). METHODS AND
      ANALYSIS: The following databases will be searched from their inception to
      January 2015: MEDLINE, EMBASE, CINAHL, AMED, Web of Science, Ovid Healthstar,
      PubMed, SciELO, the China National Knowledge Infrastructure Database, the
      Chongqing VIP Chinese Science and Technology Periodical Database, the Chinese
      Biomedical Database, the Wanfang Database, the Japanese Medical Research
      Database, and Korean Medical Databases. The methodological quality will be
      assessed using the Cochrane risk of bias tool. The primary outcome is total nasal
      symptoms, which may be evaluated by any appropriate scores or other forms of
      measurement. Secondary outcome measures will include quality of life, total non
      nasal symptoms, use of daily medication and laboratory indicators. ETHICS AND
      DISSEMINATION: Because this study will not involve patients, institutional review
      body permission is not required. The systematic review will be published in a
      peer-reviewed journal. The review will also be disseminated electronically and in
      print to help guide healthcare practice and policy. TRIAL REGISTRATION NUMBER:
      PROSPERO CRD42014013275.

PMID- 25991447
TI  - Assessment of the feasibility of an ultra-low power, wireless digital patch for
      the continuous ambulatory monitoring of vital signs.
AB  - BACKGROUND AND OBJECTIVES: Vital signs are usually recorded at 4-8 h intervals in
      hospital patients, and deterioration between measurements can have serious
      consequences. The primary study objective was to assess agreement between a new
      ultra-low power, wireless and wearable surveillance system for continuous
      ambulatory monitoring of vital signs and a widely used clinical vital signs
      monitor. The secondary objective was to examine the system's ability to
      automatically identify and reject invalid physiological data. SETTING: Single
      hospital centre. PARTICIPANTS: Heart and respiratory rate were recorded over 2 h
      in 20 patients undergoing elective surgery and a second group of 41 patients with
      comorbid conditions, in the general ward. OUTCOME MEASURES: Primary outcome
      measures were limits of agreement and bias. The secondary outcome measure was
      proportion of data rejected. RESULTS: The digital patch provided reliable heart
      rate values in the majority of patients (about 80%) with normal sinus rhythm, and
      in the presence of abnormal ECG recordings (excluding aperiodic arrhythmias such
      as atrial fibrillation). The mean difference between systems was less than +/-1
      bpm in all patient groups studied. Although respiratory data were more frequently
      rejected as invalid because of the high sensitivity of impedance pneumography to
      motion artefacts, valid rates were reported for 50% of recordings with a mean
      difference of less than +/-1 brpm compared with the bedside monitor. Correlation
      between systems was statistically significant (p<0.0001) for heart and
      respiratory rate, apart from respiratory rate in patients with atrial
      fibrillation (p=0.02). CONCLUSIONS: Overall agreement between digital patch and
      clinical monitor was satisfactory, as was the efficacy of the system for
      automatic rejection of invalid data. Wireless monitoring technologies, such as
      the one tested, may offer clinical value when implemented as part of wider
      hospital systems that integrate and support existing clinical protocols and
      workflows.

PMID- 25991448
TI  - Perspectives from health, social care and policy stakeholders on the value of a
      single self-report outcome measure across long-term conditions: a qualitative
      study.
AB  - OBJECTIVES: To explore the views of a range of stakeholders regarding whether
      patient-reported outcome measures (PROMs) can be developed to measure key
      attributes of long-term conditions (LTCs) care in England, and the potential
      value of a single generic measure. DESIGN: Qualitative semistructured interview
      study, analysed using a framework approach. PARTICIPANTS AND SETTING: Interviews
      with 31 stakeholders from primary care, secondary care, social care, policy and
      patient-focused voluntary organisations in England. RESULTS: There was broad
      support for a single PROM that could be used to measure outcomes for patients
      with any LTCs in any health or social care setting. Interviewees identified three
      desired uses for a PROM: to improve the quality of individual care; to increase
      people's engagement in their own care; and to monitor the performance of
      services. Interviewees felt that a PROM for LTCs should incorporate a mixture of
      traditional and non-traditional domains, such as functioning, empowerment and
      social participation, and be codesigned with patients and professional end-users.
      Stakeholders emphasised the need for a PROM to be feasible for practical
      implementation at the individual clinical level as a first priority. A number of
      concerns and potential problems were identified in relation to the application
      and interpretation of an LTC PROM. CONCLUSIONS: This study has demonstrated
      support for a single self-report outcome measure that reflects the priorities of
      people with LTCs, if such a measure can be shown to be meaningful and useful at
      the individual level. People with LTCs and professional end-users in health and
      social care should be involved in the development and evaluation of such a
      measure.

PMID- 25991449
TI  - Cost-effectiveness and public health benefit of secondary cardiovascular disease
      prevention from improved adherence using a polypill in the UK.
AB  - OBJECTIVE: To evaluate the public health and economic benefits of adherence to a
      fixed-dose combination polypill for the secondary prevention of cardiovascular
      (CV) events in adults with a history of myocardial infarction (MI) in the UK.
      DESIGN: Markov-model-based cost-effectiveness analysis, informed by systematic
      reviews, which identified efficacy, utilities and adherence data inputs. SETTING:
      General practice in the UK. PARTICIPANTS: Patients with a mean age of 64.7 years,
      most of whom are men with a recent or non-recent diagnosis of MI and for whom
      secondary preventive medication is indicated and well tolerated. INTERVENTION:
      Fixed-dose combination polypill (100 mg aspirin, 20 mg atorvastatin and 2.5, 5,
      or 10 mg ramipril) compared with multiple monotherapy. PRIMARY AND SECONDARY
      OUTCOME MEASURES: CV events prevented per 1000 patients; cost per life-year
      gained; and cost per quality-adjusted life-year (QALY) gained. RESULTS: The model
      estimates that for each 10% increase in adherence, an additional 6.7% fatal and
      non-fatal CV events can be prevented. In the base case, over 10 years, the
      polypill would improve adherence by ~20% and thereby prevent 47 of 323 (15%)
      fatal and non-fatal CV events per 1000 patients compared with multiple
      monotherapy, with an incremental cost-effectiveness ratio (ICER) of L8200 per
      QALY gained. Probabilistic sensitivity analyses for the base-case assumptions
      showed an 81.5% chance of the polypill being cost-effective at a willingness-to
      pay threshold of L20,000 per QALY gained compared with multiple monotherapy. In
      scenario analyses that varied structural assumptions, ICERs ranged between cost
      saving and L21,430 per QALY gained. CONCLUSIONS: Assuming that some 450,000
      adults are at risk of MI, a 10 percentage point uptake of the polypill could
      prevent 3260 CV events and 590 CV deaths over a decade.The polypill appears to be
      a cost-effective strategy to prevent fatal and non-fatal CV events in the UK.

PMID- 25991450
TI  - Occurrence and impact of negative behaviour, including domestic violence and
      abuse, in men attending UK primary care health clinics: a cross-sectional survey.
AB  - OBJECTIVE: To measure the experience and perpetration of negative behaviour,
      including domestic violence and abuse (DVA), and investigate its associations
      with health conditions and behaviours in men attending general practice. DESIGN:
      Cross-sectional questionnaire-based study conducted between September 2010 and
      June 2011. SETTING: 16 general practices in the south west of England.
      PARTICIPANTS: Male patients aged 18 or older, attending alone, who could read and
      write English. A total of 1403 of eligible patients (58%) participated in the
      survey and 1368 (56%) completed the questions relevant to this paper. 97% of
      respondents reported they were heterosexual. MAIN OUTCOME MEASURES: Lifetime
      occurrence of negative behaviour consistent with DVA, perceived health impact of
      negative behaviours, associations with anxiety and depression symptoms, and
      cannabis use in the past 12 months and binge drinking. RESULTS: 22.7% (95% CI
      20.2% to 24.9%) of men reported ever experiencing negative behaviour (feeling
      frightened, physically hurt, forced sex, ask permission) from a partner. All
      negative behaviours were associated with a twofold to threefold increased odds of
      anxiety and depression symptoms in men experiencing or perpetrating negative
      behaviours or both. 34.9% (95% CI 28.7% to 41.7%) of men who reported
      experiencing negative behaviour from a partner, and 30.8% (95% CI 23.7% to 37.8%)
      of men who perpetrated negative behaviours said they had been in a domestically
      violent or abusive relationship. No associations with problematic drinking were
      found; there was a weak association with cannabis use. CONCLUSIONS: DVA is
      experienced or perpetrated by a large minority of men presenting to general
      practice, and these men were more likely to have current symptoms of depression
      and anxiety. Presentation of anxiety or depression to clinicians may be an
      indicator of male experience or perpetration of DVA victimisation.

PMID- 25991451
TI  - Validation of the Framingham general cardiovascular risk score in a multiethnic
      Asian population: a retrospective cohort study.
AB  - OBJECTIVE: This study aims to examine the validity of the Framingham general
      cardiovascular disease (CVD) risk chart in a primary care setting. DESIGN: This
      is a 10-year retrospective cohort study. SETTING: A primary care clinic in a
      teaching hospital in Malaysia. PARTICIPANTS: 967 patients' records were randomly
      selected from patients who were attending follow-up in the clinic. MAIN OUTCOME
      MEASURES: Baseline demographic data, history of diabetes and smoking, blood
      pressure (BP), and serum lipids were captured from patient records in 1998. Each
      patient's Framingham CVD score was computed from these parameters. All
      atherosclerotic CVD events occurring between 1998 and 2007 were counted. RESULTS:
      In 1998, mean age was 57 years with 33.8% men, 6.1% smokers, 43.3% diabetics and
      59.7% hypertensive. Median BP was 140/80 mm Hg and total cholesterol 6.0 mmol/L
      (1.3). The predicted median Framingham general CVD risk score for the study
      population was 21.5% (IQR 1.2-30.0) while the actual CVD events that occurred in
      the 10 years was 13.1% (127/967). The median CVD points for men was 30.0, giving
      them a CVD risk of more than 30%; for women it is 18.5, a CVD risk of 21.5%. Our
      study found that the Framingham general CVD risk score to have moderate
      discrimination with an area under the receiver operating characteristic curve
      (AUC) of 0.63. It also discriminates well for Malay (AUC 0.65, p=0.01), Chinese
      (AUC 0.60, p=0.03), and Indians (AUC 0.65, p=0.001). There was good calibration
      with Hosmer-Lemeshow test chi(2)=3.25, p=0.78. CONCLUSIONS: Taking into account
      that this cohort of patients were already on treatment, the Framingham General
      CVD Risk Prediction Score predicts fairly accurately for men and overestimates
      somewhat for women. In the absence of local risk prediction charts, the
      Framingham general CVD risk prediction chart is a reasonable alternative for use
      in a multiethnic group in a primary care setting.

PMID- 25991452
TI  - Workload and management of childhood fever at general practice out-of-hours care:
      an observational cohort study.
AB  - OBJECTIVE: Even though childhood fever is mostly self-limiting, children with
      fever constitute a considerable workload in primary care. Little is known about
      the number of contacts and management during general practitioners' (GPs) out-of
      hours care. We investigated all fever related telephone contacts, consultations,
      antibiotic prescriptions and paediatric referrals of children during GP out-of
      hours care within 1 year. DESIGN: Observational cohort study. SETTING AND
      PATIENTS: We performed an observational cohort study at a large Dutch GP out-of
      hours service. Children (<12 years) whose parents contacted the GP out-of-hours
      service for a fever related illness in 2012 were included. MAIN OUTCOME MEASURES:
      Number of contacts and consultations, antibiotic prescription rates and
      paediatric referral rates. RESULTS: We observed an average of 14.6 fever related
      contacts for children per day at GP out-of-hours services, with peaks during
      winter months. Of 17,170 contacts in 2012, 5343 (31.1%) were fever related and
      70.0% resulted in a GP consultation. One in four consultations resulted in an
      antibiotic prescription. Prescriptions increased by age and referrals to
      secondary care decreased by age (p<0.001). The majority of parents (89.5%)
      contacted the out-of-hours service only once during a fever episode (89.5%) and
      7.6% of children were referred to secondary care. CONCLUSIONS: This study shows
      that childhood fever does account for a large workload at GP out-of-hours
      services. One in three contacts is fever related and 70% of those febrile
      children are called in to be assessed by a GP. One in four consultations for
      childhood fever results in antibiotic prescribing and most consultations are
      managed in primary care without referral.

PMID- 25991453
TI  - Longitudinal impact of demographic and clinical variables on health-related
      quality of life in cystic fibrosis.
AB  - OBJECTIVES: The insights that people with cystic fibrosis have concerning their
      health are important given that aspects of health-related quality of life (HRQoL)
      are independent predictors of survival and a decrease in lung function is
      associated with a decrease in HRQoL over time. Cross-sectional data suggest that
      key variables, other than lung function, are also associated with HRQoL--although
      study results are equivocal. This work evaluates the relationship between these
      key demographic and clinical variables and HRQoL longitudinally. DESIGN:
      Longitudinal observational study. Observations were obtained at seven time
      points: approximately every 2 years over a 12-year period. SETTING: Large adult
      cystic fibrosis centre in the UK. PARTICIPANTS: 234 participants aged 14-48 years
      at recruitment. OUTCOME MEASURE: Nine domains of HRQoL (Cystic Fibrosis Quality
      of Life Questionnaire) in relation to demographic (age, gender) and clinical
      measures (forced expiratory volume in 1 s, (FEV1)% predicted, body mass index
      (BMI), cystic fibrosis-related diabetes, Burkholderia cepacia complex, totally
      implantable vascular access device, nutritional and transplant status). RESULTS:
      A total of 770 patient assessments were obtained for 234 patients. The results of
      random coefficients modelling indicated that demographic and clinical variables
      were identified as being significant for HRQoL over time. In addition to lung
      function, transplant status, age, having a totally implantable vascular access
      device, cystic fibrosis-related diabetes, BMI and B. cepacia complex impacted on
      many HRQoL domains longitudinally. Gender was important for the domain of body
      image. CONCLUSIONS: Demographic and changes in clinical variables were
      independently associated with a change in HRQoL over time. Compared with these
      longitudinal data, cross-sectional data are inadequate when evaluating the
      relationships between HRQoL domains and key demographic and clinical variables,
      as they fail to recognise the full impact of the CF disease trajectory and its
      treatments on quality of life.

PMID- 25991454
TI  - What do you think overdiagnosis means? A qualitative analysis of responses from a
      national community survey of Australians.
AB  - OBJECTIVE: Overdiagnosis occurs when someone is diagnosed with a disease that
      will not harm them. Against a backdrop of growing evidence and concern about the
      risk of overdiagnosis associated with certain screening activities, and
      recognition of the need to better inform the public about it, we aimed to ask
      what the Australian community understood overdiagnosis to mean. DESIGN, SETTING
      AND PARTICIPANTS: Content analysis of verbatim responses from a randomly sampled
      community telephone survey of 500 Australian adults, between January and February
      2014. Data were analysed independently by two researchers. MAIN OUTCOME MEASURES:
      Analysis of themes arising from community responses to open-ended questions about
      the meaning of overdiagnosis. RESULTS: The sample was broadly representative of
      the Australian population. Forty per cent of respondents thought overdiagnosis
      meant exaggerating a condition that was there, diagnosing something that was not
      there or too much diagnosis. Twenty-four per cent described overdiagnosis as
      overprescribing, overtesting or overtreatment. Only 3% considered overdiagnosis
      meant doctors gained financially. No respondents mentioned screening in
      conjunction with overdiagnosis, and over 10% of participants were unable to give
      an answer. CONCLUSIONS: Around half the community surveyed had an approximate
      understanding of overdiagnosis, although no one identified it as a screening risk
      and a quarter equated it with overuse. Strategies to inform people about the risk
      of overdiagnosis associated with screening and diagnostic tests, in clinical and
      public health settings, could build on a nascent understanding of the nature of
      the problem.

PMID- 25991455
TI  - Work-related allergies to storage mites in Parma (Italy) ham workers.
AB  - OBJECTIVES: To investigate the role of storage mites in the development of
      allergic diseases among ham production workers, and to search for early
      alterations in lung function tests and early inflammation markers in exhaled air.
      Respiratory allergies due to storage mites have been reported in people with
      various occupations but, although such mites are unavoidable when curing ham,
      there are no published data concerning ham production workers. SETTING: Secondary
      care. DESIGN: Experimental cross-sectional study. PARTICIPANTS: 220 participants
      (110 ham production workers and 110 controls) were recruited. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Workers answered a medical questionnaire, and
      underwent spirometry and fraction of exhaled nitric oxide at 50 mL/s (FeNO50)
      measurements. Those with allergic symptoms also underwent skin prick tests to
      determine their sensitisation to airborne allergens. A methacholine test was
      performed in symptomatic participants when spirometry was normal to assess
      airways hyper-responsiveness. RESULTS: Symptomatic storage mite sensitisation was
      observed in 16 workers (14.5%) (rhinoconjunctivitis in 15 (63%) and asthma in
      (4%)) and 2 controls (1.8%; p=0.001). Higher FeNO50 values in exposed symptomatic
      workers compared with healthy control participants (34.65+/-7.49 vs 13.29+/-4.29
      ppb; p<0.001) suggested bronchial and nasal involvement, although their lung
      function parameters were normal. Regardless of exposure, a FeNO50 value of 22.5
      ppb seems to be 100% sensitive and 99.4% specific in distinguishing allergic and
      non-allergic participants. Multivariate analysis of FeNO50 values in the
      symptomatic participants showed that they were positively influenced by IgE
      mediated allergy (p=0.001) and reported symptom severity (p=0.041), and
      negatively by smoking status (p=0.049). CONCLUSIONS: Ham processing workers, as
      well as workers involved in any meat processing work that includes curing, should
      be informed about the occupational risk of sensitisation to mites.

PMID- 25991456
TI  - DNA sequence analysis and genotype-phenotype assessment in 71 patients with
      syndromic hearing loss or auditory neuropathy.
AB  - OBJECTIVES: Aetiological assessment of 71 probands whose clinical presentation
      suggested a genetic syndrome or auditory neuropathy. METHODS: Sanger sequencing
      was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines.
      Genes were selected for sequencing based on each patient's clinical presentation
      and suspected diagnosis. Observed DNA sequence variations were assessed for
      pathogenicity by review of the scientific literature, and mutation and
      polymorphism databases, through the use of in silico tools including sorting
      intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), and
      according to the recommendations of the American College of Medical Genetics and
      Genomics for the interpretation of DNA sequence variations. Novel DNA sequence
      variations were sought in controls. RESULTS: DNA sequencing of the coding and
      near-coding regions of genes relevant to each patient's clinical presentation
      revealed 37 sequence variations of known or uncertain pathogenicity in 9 genes
      from 25 patients. 14 novel sequence variations were discovered. Assessment of
      phenotypes revealed notable findings in 9 patients. CONCLUSIONS: DNA sequencing
      in patients whose clinical presentation suggested a genetic syndrome or auditory
      neuropathy provided opportunities for aetiological assessment and more precise
      genetic counselling of patients and families. The failure to identify a genetic
      aetiology in many patients in this study highlights the extreme heterogeneity of
      genetic hearing loss, the incompleteness of current knowledge of aetiologies of
      hearing loss, and the limitations of conventional DNA sequencing strategies that
      evaluate only coding and near-coding segments of genes.

PMID- 25991457
TI  - Professionalism dilemmas, moral distress and the healthcare student: insights
      from two online UK-wide questionnaire studies.
AB  - OBJECTIVE: To understand the prevalence of healthcare students' witnessing or
      participating in something that they think unethical (professionalism dilemmas)
      during workplace learning and examine whether differences exist in moral distress
      intensity resulting from these experiences according to gender and the frequency
      of occurrence. DESIGN: Two cross-sectional online questionnaires of UK medical
      (study 1) and nursing, dentistry, physiotherapy and pharmacy students (study 2)
      concerning professionalism dilemmas and subsequent distress for (1) Patient
      dignity and safety breaches; (2) Valid consent for students' learning on
      patients; and (3) Negative workplace behaviours (eg, student abuse). PARTICIPANTS
      AND SETTING: 2397 medical (67.4% female) and 1399 other healthcare students
      (81.1% female) responded. MAIN RESULTS: The most commonly encountered
      professionalism dilemmas were: student abuse and patient dignity and safety
      dilemmas. Multinomial and logistic regression identified significant effects for
      gender and frequency of occurrence. In both studies, men were more likely to
      classify themselves as experiencing no distress; women were more likely to
      classify themselves as distressed. Two distinct patterns concerning frequency
      were apparent: (1) Habituation (study 1): less distress with increased exposure
      to dilemmas 'justified' for learning; (2) Disturbance (studies 1 and 2): more
      distress with increased exposure to dilemmas that could not be justified.
      CONCLUSIONS: Tomorrow's healthcare practitioners learn within a workplace in
      which they frequently encounter dilemmas resulting in distress. Gender
      differences could be respondents acting according to gendered expectations (eg,
      males downplaying distress because they are expected to appear tough).
      Habituation to dilemmas suggests students might balance patient autonomy and
      right to dignity with their own needs to learn for future patient benefit.
      Disturbance contests the 'accepted' notion that students become less empathic
      over time. Future research might examine the strategies that students use to
      manage their distress, to understand how this impacts of issues such as burnout
      and/or leaving the profession.

PMID- 25991458
TI  - Why do patients with 'primary care sensitive' problems access ambulance services?
      A systematic mapping review of the literature.
AB  - OBJECTIVE: Emergency ambulance use for problems that could be managed in primary
      care continues to rise owing to complex reasons that are poorly understood. The
      objective of this systematic review is to draw together published evidence across
      a variety of study methodologies and settings to gain a better understanding of
      why patients seek help from ambulance services for these problems. DESIGN:
      Systematic searches were undertaken across the MEDLINE, EMBASE, PsychINFO,
      CINAHL, Health Management Information Consortium and Health Management
      Information Service publication databases. Google Scholar, Web of Science,
      OpenSigle, EThOS and DART databases were also systematically searched for
      reports, proceedings, book chapters and theses, along with hand-searching of grey
      literature sources. Studies were included if they reported on findings examining
      patient, carer, health professional or service management interactions with
      ambulance services for primary care problems. All study methodologies and
      perspectives were of interest. Data were extracted, quality assessed and
      systematically mapped according to key findings through generation of an
      iterative framework. RESULTS: A total of 31 studies met inclusion criteria.
      Findings were summarised across 5 broad categories: factors associated with
      individual patients; actions of care-givers and bystanders; population-level
      factors; health infrastructure factors; challenges faced by health professionals.
      A number of subcategories were developed to explore these factors in more detail.
      CONCLUSIONS: This review reports important factors that may impact on ambulance
      use for primary care problems across a global setting, including demographic
      measures associated with deprivation, minority status and individual social
      circumstances. Categorising ambulance calls for primary care problems as
      'inappropriate' is context dependant and may be unhelpful. Potential implications
      for triage and risk management strategies are discussed.

PMID- 25991459
TI  - Predictors of skilled attendance at delivery among antenatal clinic attendants in
      Ghana: a cross-sectional study of population data.
AB  - OBJECTIVE: To identify demographic, maternal and community predictors of skilled
      attendance at delivery among women who attend antenatal clinic at least once
      during their pregnancy in Ghana. DESIGN: A cross-sectional study using the 2008
      Ghana Demographic and Health Survey (DHS) data. We used frequencies for
      descriptive analysis, chi(2) test for associations and logistic regression to
      identify significant predictors. Predictive models were built with estimation of
      area under the receiver operating characteristic curves (AUC). SETTING: Ghana.
      PARTICIPANTS: A total of 2041 women who had a live birth in the 5 years preceding
      the survey, and attended an antenatal clinic having a skilled provider, at least
      once, during the pregnancy. OUTCOME: Skilled attendance at delivery. RESULTS:
      Overall, 60.5% (1235/2041) of women in our study sample reported skilled
      attendance at delivery. Significant positive associations existed between skilled
      attendance at delivery and the variables such as maternal educational level,
      wealth status class, ever use of contraception, previous pregnancy complications
      and health insurance coverage (p<0.001). Significant predictors of skilled
      attendance were wealth status class, residency, previous delivery complication,
      health insurance coverage and religion in a model with AUC (95% CI) of 0.85 (0.83
      to 0.88). CONCLUSIONS: Women less likely to have skilled attendance at delivery
      can be identified during antenatal care by using data on wealth status class,
      health insurance coverage, residence, history of previous birth complications and
      religion, and targeted with interventions to improve skilled attendance at
      delivery.

PMID- 25991460
TI  - The diagnostic accuracy of chest ultrasound for CT-detected radiographic
      consolidation in hospitalised adults with acute respiratory failure: a systematic
      review.
AB  - OBJECTIVES: (1) Summarise chest ultrasound accuracy to diagnose radiological
      consolidation, referenced to chest CT in patients with acute respiratory failure
      (ARF). (2) Directly compared ultrasound with chest X-ray. SETTING: Hospitalised
      patients. PARTICIPANTS: Studies were eligible if adult participants in
      respiratory failure underwent chest ultrasound to diagnose consolidation
      referenced to CT. Exclusion: (1) not primary study, (2) not respiratory failure,
      (3) not chest ultrasound, (4) not consolidation, (5) translation unobtainable,
      (6) unable to extract data, (7) unable to obtain paper. 4 studies comprising 224
      participants met inclusion. OUTCOME MEASURES: As planned, paired forest plots
      display 95% CIs of sensitivity and specificity for ultrasound and chest X-ray.
      Sensitivity and specificity from each study are plotted in receiver operator
      characteristics space. Meta-analysis was planned if studies were sufficiently
      homogeneous and numerous (>=4). Although this numerical requirement was met, meta
      analysis was prevented by heterogeneous units of analysis between studies.
      RESULTS: All studies were in intensive care, with either a high risk of selection
      bias or high applicability concerns. Studies had unclear or high risk of bias
      related to use of ultrasound. Only 1 study clearly performed ultrasound within 24
      h of respiratory failure diagnosis. Ultrasound sensitivity ranged from 0.91 (95%
      CI 0.81 to 0.97) to 1.00 (95% CI 0.95 to 1.00). Specificity ranged from 0.78 (95%
      CI 0.52 to 0.94) to 1.00 (0.99 to 1.00). In two studies, chest X-ray had lower
      sensitivity than ultrasound, but there were insufficient patients to compare
      specificity. CONCLUSIONS: Four small studies suggest ultrasound is highly
      sensitive and specific for consolidation in ARF, but high risk of bias and
      concerns about applicability in all studies may have inflated diagnostic
      accuracy. Further robustly designed studies are needed to define the role of
      ultrasound in this setting. TRIAL REGISTRATION NUMBER:
      http://www.crd.york.ac.uk/PROSPERO/ (CRD42013006472).

PMID- 25991461
TI  - Wraparound care for youth injured by violence: study protocol for a pilot
      randomised control trial.
AB  - INTRODUCTION: Injury by violence is the fourth cause of death and the leading
      reason for a youth to visit an emergency department (ED) in Canada. In Winnipeg,
      20% of youth who visit an ED with an injury due to violence have a second visit
      for a subsequent violent injury within 1 year. Youth injured by violence are in a
      reflective and receptive state of mind, rendering the ED setting appropriate for
      intervention. METHODS AND ANALYSIS: This protocol describes a wraparound care
      model delivered by a support worker with lived experience with violence,
      supported by social workers and links to multiple community partners. Support
      workers will be on call 24 h a day, 7 days a week in order to start the
      intervention in the ED and take advantage of the 'teachable moment'. The protocol
      is of a pilot randomised control trial to assess the feasibility of a randomised
      control trial designed to assess efficacy. For the pilot trial, we will assess
      recruitment, treatment fidelity, participant adherence and safety. The
      intervention arm will receive wraparound care initiated at the time of their
      visit for injury due to violence. The control arm will receive standard care. We
      will use an adapted preconsent randomisation methodology. This intervention has
      been developed using an integrated knowledge translation approach. DISCUSSION:
      Interventions delivered in the ED for youth injured by violence require an
      approach that is appropriate for the unique situation the youth are in. ETHICS:
      The University of Manitoba Health Research Ethics Board (HS 16445 (Cohort study)
      and HS 16444 (WrapAround Care study) granted ethical approval. TRIAL REGISTRATION
      NUMBER: NCT01895738.

PMID- 25991463
TI  - The Nlrp3 inflammasome admits defeat.
AB  - The Nlrp3 inflammasome triggers interleukin-1 secretion by myeloid cells in
      response to endogenous and exogenous danger signals. Two recent studies
      identified the sulfonylurea MCC950 and the ketone metabolite beta-hydroxybutyrate
      as specific inhibitors of the Nlrp3 inflammasome, with promising therapeutic
      potential for the treatment of auto-inflammatory diseases. 

PMID- 25991462
TI  - Mutation-targeted therapy with sunitinib or everolimus in patients with advanced
      low-grade or intermediate-grade neuroendocrine tumours of the gastrointestinal
      tract and pancreas with or without cytoreductive surgery: protocol for a phase II
      clinical trial.
AB  - INTRODUCTION: Finding the optimal management strategy for patients with advanced,
      metastatic neuroendocrine tumours (NETs) of the gastrointestinal tract and
      pancreas is a work in progress. Sunitinib and everolimus are currently approved
      for the treatment of progressive, unresectable, locally advanced or metastatic
      low-grade or intermediate-grade pancreatic NETs. However, mutation-targeted
      therapy with sunitinib or everolimus has not been studied in this patient
      population. METHODS AND ANALYSIS: This prospective, open-label phase II clinical
      trial was designed to determine if mutation-targeting therapy with sunitinib or
      everolimus for patients with advanced low-grade or intermediate-grade NETs is
      more effective than historically expected results with progression-free survival
      (PFS) as the primary end point. Patients >=18 years of age with progressive, low
      grade or intermediate-grade locally advanced or metastatic NETs are eligible for
      this study. Patients will undergo tumour biopsy (if they are not a surgical
      candidate) for tumour genotyping. Patients will be assigned to sunitininb or
      everolimus based on somatic/germline mutations profile. Patients who have disease
      progression on either sunitinib or everolimus will crossover to the other drug.
      Treatment will continue until disease progression, unacceptable toxicity, or
      consent to withdrawal. Using the proposed criteria, 44 patients will be accrued
      within each treatment group during a 48-month period (a total of 88 patients for
      the 2 treatments), and followed for up to an additional 12 months (a total of 60
      months from entry of the first patient) to achieve 80% power in order to test
      whether there is an improvement in PFS compared to historically expected results,
      with a 0.10 alpha level one-sided significance test. ETHICS AND DISSEMINATION:
      The study protocol was approved by the institutional review board of the National
      Cancer Institute (NCI-IRB Number 15C0040; iRIS Reference Number 339636). The
      results will be published in a peer-reviewed journal and shared with the
      worldwide medical community. TRIAL REGISTRATION NUMBER: NCT02315625.

PMID- 25991464
TI  - Supplementation with rumen-protected L-arginine-HCl increased fertility in sheep
      with synchronized estrus.
AB  - The aim of the present study was to evaluate the effects of L-arginine-HCl
      supplementation on ovulation rate, fertility, prolificacy, and serum VEGF
      concentrations in ewes with synchronized oestrus. Thirty Suffolk ewes with a mean
      body weight of 45 +/- 3 kg and a mean body condition score (BCS) of 2.4 +/- 0.28
      were synchronized for estrus presentation with a progestin-containing sponge (20
      mg Chronogest(r) CR) for 9 days plus PGF2-alpha (Lutalyse; Pfizer, USA) on day 7
      after the insertion of the sponge. The ewes were divided into two groups; i.e., a
      control group (n = 15) that was fed on the native pasture (basal diet) and an L
      arginine-HCl group (n = 15) that received 7.8 g of rumen-protected L-arginine-HCl
      from day 5 of the sponge insertion until day 25 after mating plus the basal diet.
      The L-arginine-HCl was administered daily via an esophageal probe between days 5
      and 9 of the synchronization protocol and every third day subsequently. Blood
      samples were drawn from the jugular vein every 6 days throughout the entire
      experimental period. The results revealed that the L-arginine-HCl supplementation
      increased fertility during the synchronized estrus (P = 0.05). However, no
      effects were observed on the final BCS (P = 0.78), estrus presentation (P =
      0.33), multiple ovulations (P = 0.24), prolificacy (P = 0.63), or serum VEGF
      concentration. In conclusion, L-arginine-HCl supplementation during the period
      used in this study increased fertility in sheep with synchronized estrus possibly
      due to improved embryo-fetal survival during early pregnancy.

PMID- 25991465
TI  - Field Evaluation of Capillary Blood Samples as a Collection Specimen for the
      Rapid Diagnosis of Ebola Virus Infection During an Outbreak Emergency.
AB  - BACKGROUND: Reliable reverse transcription polymerase chain reaction (RT-PCR)
      based diagnosis of Ebola virus infection currently requires a blood sample
      obtained by intravenous puncture. During the current Ebola outbreak in Guinea, we
      evaluated the usability of capillary blood samples collected from fingersticks of
      patients suspected of having Ebola virus disease (EVD) for field diagnostics
      during an outbreak emergency. METHODS: A total of 120 venous and capillary blood
      samples were collected from 53 patients admitted to the Ebola Treatment Centre in
      Gueckedou, Guinea, between July and August 2014. All sample specimens were
      analyzed by RT-PCR using the RealStar Filovirus Screen RT-PCR Kit 1.0 from altona
      Diagnostics (Germany). We compared samples obtained by venipuncture and those
      obtained by capillary blood sampling absorbed onto swab devices. RESULTS: The
      resulting sensitivity and specificity of tests performed with capillary blood
      samples were 86.8% (95% confidence interval [CI], 71.9%-95.6%; 33/38 patients)
      and 100% (95% CI, 84.6%-100%; 22/22 patients), respectively. CONCLUSIONS: Our
      data suggest that capillary blood samples could serve as an alternative to venous
      blood samples for the diagnosis of EVD in resource-limited settings during a
      crisis. This can be of particular advantage in cases when venipuncture is
      difficult to perform-for example, with newborns and infants or when adult
      patients reject venipuncture for cultural or religious reasons.

PMID- 25991466
TI  - Diagnosis of Febrile Illnesses Other Than Ebola Virus Disease at an Ebola
      Treatment Unit in Sierra Leone.
AB  - Patients with febrile illnesses presenting to an Ebola treatment unit in Sierra
      Leone had a wide range of diagnoses other than Ebola virus disease. Rapid
      diagnostic tests were useful in confirming these diagnoses, reducing the length
      of patient stay with valuable consequences. These alternative diagnoses should
      assist in future planning. 

PMID- 25991467
TI  - Editorial Commentary: The Irreversibility of HIV Drug Resistance.

PMID- 25991468
TI  - Administration of Brincidofovir and Convalescent Plasma in a Patient With Ebola
      Virus Disease.
AB  - From 2014 to May 2015, >26 000 Ebola virus disease (EVD) cases were reported from
      West Africa. We present a patient with EVD who received brincidofovir and
      convalescent plasma. The relative contributions of supportive care,
      investigational therapies, and patient's immune-response on survival could not be
      determined. Randomized trials are needed.

PMID- 25991469
TI  - Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1
      Infection.
AB  - BACKGROUND: Prospectively and systematically collected data on frequency and
      spectrum of unexpected clinical manifestations during primary human
      immunodeficiency virus (HIV) infection (PHI) have not been published. METHODS: We
      prospectively enrolled 290 patients with documented PHI in the Zurich Primary HIV
      Infection Study. Typical acute retroviral syndrome (ARS) was defined as fever
      plus at least 1 symptom or sign typically considered to be associated with ARS;
      in absence of fever, presence of 2 or more ARS symptoms or signs. Atypical ARS
      was defined as lack of symptoms or signs, a single symptom or sign only and
      absence of fever, presence of symptoms or signs that are not considered typically
      associated with ARS, or occurrence of an opportunistic disease. Time to diagnosis
      was calculated based on estimated date of infection and first positive HIV test.
      RESULTS: We analyzed 290 patients (271 males). PHI manifested with typical ARS in
      202 (70%) and with atypical ARS in 88 (30%) patients. Patients with atypical ARS
      were hospitalized 4 times more often compared with typical ARS (43% vs 11%; P <
      .001). The gastrointestinal tract was the most frequent organ system affected in
      patients with atypical manifestations. Only in 112 (38%) patients was HIV
      infection suspected during the first medical attendance. Patients with typical
      ARS were diagnosed slightly earlier compared with atypical ARS, but this
      difference was not significant (P = .3). CONCLUSIONS: Unexpected clinical
      presentations occurred in a large fraction of patients with PHI and were
      associated with substantial morbidity. Universal HIV testing may be mandatory in
      high-risk groups.

PMID- 25991470
TI  - Evidence of Self-Sustaining Drug Resistant HIV-1 Lineages Among Untreated
      Patients in the United Kingdom.
AB  - BACKGROUND: About 10% of new diagnoses of subtype B human immunodeficiency virus
      type 1 (HIV-1) in the United Kingdom are with viruses showing transmitted drug
      resistance (TDR). However, there is discordance between the mutation patterns
      observed in HIV-infected patients failing therapy and those seen in TDR. METHODS:
      We extracted all subtype B HIV-1 pol gene sequences from treatment-naive patients
      within the United Kingdom HIV Drug Resistance Database sampled between 1997 and
      2011 and carrying the most common protease inhibitors, nonnucleoside and
      nucleotide reverse transcriptase inhibitors TDR mutations, namely, L90M, K103N,
      and T215Y/F/rev, respectively (n = 1140). Transmission clusters (n >= 2
      sequences) were identified by maximum-likelihood phylogeny using a genetic
      distance cutoff of <= 1.5%. The time of origin and the basic reproductive number
      (R0) of clusters were estimated by Bayesian methods. RESULTS: T215rev was present
      alone in 47% of the sequences (n = 540), K103N in 31% (n = 359), and L90M in 10%
      (n = 109). The remaining sequences contained T215Y or combinations of L90M,
      K103N, and T215rev. Fifty-five percent (n = 624) of the sequences formed highly
      supported transmission clusters (n = 193) containing between 2 and 15 sequences.
      The time of origin of 10 large clusters (>= 8 sequences) was estimated to be
      between 2000 (1999-2002; 95% highest posterior density [HPD]) and 2006 (2005
      2007; 95% HPD). The oldest cluster had persisted for nearly 8 years. All 10
      clusters had R0s ranging from 1.3 (0.4-2.5; 95% HPD) to 2.8 (0.6-6.5; 95% HPD).
      CONCLUSIONS: A high proportion of the most common TDR in subtype B infections in
      the United Kingdom is derived by onward transmission from treatment-naive
      patients.

PMID- 25991471
TI  - Improving Clinical Outcomes in Patients With Methicillin-Sensitive Staphylococcus
      aureus Bacteremia and Reported Penicillin Allergy.
AB  - BACKGROUND: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a
      morbid infection. First-line MSSA therapies (nafcillin, oxacillin, cefazolin) are
      generally avoided in the 10% of patients reporting penicillin (PCN) allergy, but
      most of these patients are not truly allergic. We used a decision tree with
      sensitivity analyses to determine the optimal evaluation and treatment for
      patients with MSSA bacteremia and reported PCN allergy. METHODS: Our model
      simulates 3 strategies: (1) no allergy evaluation, give vancomycin (Vanc); (2)
      allergy history-guided treatment: if history excludes anaphylactic features, give
      cefazolin (Hx-Cefaz); and (3) complete allergy evaluation with history
      appropriate PCN skin testing: if skin test negative, give cefazolin (ST-Cefaz).
      Model outcomes included 12-week MSSA cure, recurrence, and death; allergic
      reactions including major, minor, and potentially iatrogenic; and adverse drug
      reactions. RESULTS: Vanc results in the fewest patients achieving MSSA cure and
      the highest rate of recurrence (67.3%/14.8% vs 83.4%/9.3% for Hx-Cefaz and
      84.5%/8.9% for ST-Cefaz) as well as the greatest frequency of allergic reactions
      (3.0% vs 2.4% for Hx-Cefaz and 1.7% for ST-Cefaz) and highest rates of adverse
      drug reactions (5.2% vs 4.6% for Hx-Cefaz and 4.7% for ST-Cefaz). Even in a "best
      case for Vanc" scenario, Vanc yields the poorest outcomes. ST-Cefaz is preferred
      to Hx-Cefaz although sensitive to input variations. CONCLUSIONS: Patients with
      MSSA bacteremia and a reported PCN allergy should have the allergy addressed for
      optimal treatment. Full allergy evaluation with skin testing seems to be
      preferred, although more data are needed.

PMID- 25991472
TI  - Expression of NKp30, NKp46 and DNAM-1 activating receptors on resting and IL-2
      activated NK cells from healthy donors according to CMV-serostatus and age.
AB  - Human natural killer (NK) cells are innate lymphoid cells with capacity to kill
      tumor cells and virus-infected cells. According to the expression of CD56 and
      CD16 several NK cell subsets have been identified, a major CD56dimCD16+
      subpopulation characterized by higher cytotoxic capacity, two CD56bright subsets
      (CD16-and CD16+) that represent different maturation stages and the fourth CD56
      CD16+ subset that correspond to activated dysfunctional NK cells. Previous
      studies have shown quantitative changes in the frequency, phenotype and
      distribution of NK cell subsets depending on CMV-serostatus and age. We have
      analyzed the expression of NKp30, NKp46 and DNAM-1 NK activating receptors on
      resting and IL-2 activated NK cells from CMV-seronegative and seropositive
      healthy young donors and from CMV-seropositive elderly individuals. Our results
      showed that CMV-serostatus of healthy young donors is associated with phenotypic
      differences on both CD56bright and CD56dim NK cells with an increase of NKp46 and
      a decrease of NKp30 expression respectively. A reduced expression of DNAM-1
      related to ageing and a lower NKp30 expression associated with CMV-seropositivity
      were observed. The expression of NKp46 and NKp30 was lower in CD57+ NK cells
      while the expression of DNAM-1 was increased. In vitro NK cell activation by IL-2
      increased the expression of NKp46 and NKp30. In summary, both age and CMV
      serostatus influence the expression of these cytotoxicity activating receptors
      that will have functional consequences. In elderly donors is difficult to isolate
      age from the effect of chronic CMV infection since in our study all elderly
      donors were CMV-seropositive. The possibility of modulating the expression of
      these activating receptors by cytokines such as IL-2 may open new opportunities
      for improving age-associated deterioration of NK cell function. 

PMID- 25991473
TI  - Complex systems dynamics in aging: new evidence, continuing questions.
AB  - There have long been suggestions that aging is tightly linked to the complex
      dynamics of the physiological systems that maintain homeostasis, and in
      particular to dysregulation of regulatory networks of molecules. This review
      synthesizes recent work that is starting to provide evidence for the importance
      of such complex systems dynamics in aging. There is now clear evidence that
      physiological dysregulation--the gradual breakdown in the capacity of complex
      regulatory networks to maintain homeostasis--is an emergent property of these
      regulatory networks, and that it plays an important role in aging. It can be
      measured simply using small numbers of biomarkers. Additionally, there are
      indications of the importance during aging of emergent physiological processes,
      functional processes that cannot be easily understood through clear metabolic
      pathways, but can nonetheless be precisely quantified and studied. The overall
      role of such complex systems dynamics in aging remains an important open
      question, and to understand it future studies will need to distinguish and
      integrate related aspects of aging research, including multi-factorial theories
      of aging, systems biology, bioinformatics, network approaches, robustness, and
      loss of complexity.

PMID- 25991474
TI  - Human gamma delta T cells: Evolution and ligand recognition.
AB  - The gammadelta T cell lineage in humans remains much of an enigma due to the low
      number of defined antigens, the non-canonical ways in which these cells respond
      to their environment and difficulty in tracking this population in vivo. In this
      review, we survey a comparative evolutionary analysis of the primate V, D and J
      gene segments and contrast these findings with recent progress in defining
      antigen recognition by different populations of gammadelta T cells in humans.
      Signatures of both purifying and diversifying selection at the Vdelta and Vgamma
      gene loci are placed into context of Vdelta1+ gammadelta T cell recognition of
      CD1d presenting different lipids, and Vgamma 9Vdelta2 T cell modulation by
      pyrophosphate-based phosphoantigens through the butyrophilins BTN3A. From this
      comparison, it is clear that co-evolution between gammadelta TCRs and these
      ligands is likely occurring, but the diversity inherent in these recombined
      receptors is an important feature in ligand surveillance. 

PMID- 25991476
TI  - Haralick texture analysis of prostate MRI: utility for differentiating non
      cancerous prostate from prostate cancer and differentiating prostate cancers with
      different Gleason scores.
AB  - OBJECTIVES: To investigate Haralick texture analysis of prostate MRI for cancer
      detection and differentiating Gleason scores (GS). METHODS: One hundred and forty
      seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI.
      Cancers >=0.5 ml and non-cancerous peripheral (PZ) and transition (TZ) zone
      tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps,
      using whole-mount pathology as reference. Texture features (Energy, Entropy,
      Correlation, Homogeneity, Inertia) were extracted and analysed using generalized
      estimating equations. RESULTS: PZ cancers (n = 143) showed higher Entropy and
      Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous
      tissue on T2WI and ADC maps (p-values: <.0001-0.008). In TZ cancers (n = 43) we
      observed significant differences for all five texture features on the ADC map
      (all p-values: <.0001) and for Correlation (p = 0.041) and Inertia (p = 0.001) on
      T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: p = 0.0225;
      6 vs. >7: p = 0.0069) and lower Energy (GS 6 vs. 7: p = 0.0116, 6 vs. >7: p =
      0.0039). ADC map Energy (p = 0.0102) and Entropy (p = 0.0019) were significantly
      different in GS <=3 + 4 versus >=4 + 3 cancers; ADC map Entropy remained
      significant after controlling for the median ADC (p = 0.0291). CONCLUSION:
      Several Haralick-based texture features appear useful for prostate cancer
      detection and GS assessment. KEY POINTS: * Several Haralick texture features may
      differentiate non-cancerous and cancerous prostate tissue. * Tumour Energy and
      Entropy on ADC maps correlate with Gleason score. * T2w-image-derived texture
      features are not associated with the Gleason score.

PMID- 25991475
TI  - Telocyte dynamics in psoriasis.
AB  - The presence of telocytes (TCs) as distinct interstitial cells was previously
      documented in human dermis. TCs are interstitial cells completely different than
      dermal fibroblasts. TCs are interconnected in normal dermis in a 3D network and
      may be involved in skin homeostasis, remodelling, regeneration and repair. The
      number, distribution and ultrastructure of TCs were recently shown to be affected
      in systemic scleroderma. Psoriasis is a common inflammatory skin condition
      (estimated to affect about 0.1-11.8% of population), a keratinization disorder on
      a genetic background. In psoriasis, the dermis contribution to pathogenesis is
      frequently eclipsed by remarkable epidermal phenomena. Because of the particular
      distribution of TCs around blood vessels, we have investigated TCs in the dermis
      of patients with psoriasis vulgaris using immunohistochemistry (IHC),
      immunofluorescence (IF), and transmission electron microscopy (TEM). IHC and IF
      revealed that CD34/PDGFRalpha-positive TCs are present in human papillary dermis.
      More TCs were present in the dermis of uninvolved skin and treated skin than in
      psoriatic dermis. In uninvolved skin, TEM revealed TCs with typical
      ultrastructural features being involved in a 3D interstitial network in close
      vicinity to blood vessels in contact with immunoreactive cells in normal and
      treated skin. In contrast, the number of TCs was significantly decreased in
      psoriatic plaque. The remaining TCs demonstrated multiple degenerative features:
      apoptosis, membrane disintegration, cytoplasm fragmentation and nuclear
      extrusion. We also found changes in the phenotype of vascular smooth muscle cells
      in small blood vessels that lost the protective envelope formed by TCs.
      Therefore, impaired TCs could be a 'missed' trigger for the characteristic
      vascular pathology in psoriasis. Our data explain the mechanism of Auspitz's
      sign, the most pathognomonic clinical sign of psoriasis vulgaris. This study
      offers new insights on the cellularity of psoriatic lesions and we suggest that
      TCs should be considered new cellular targets in forthcoming therapies. 

PMID- 25991477
TI  - Value of CT to predict surgically important bowel and/or mesenteric injury in
      blunt trauma: performance of a preliminary scoring system.
AB  - OBJECTIVES: To evaluate the performance of a computed tomography (CT) diagnostic
      score to predict surgical treatment for blunt bowel and/or mesentery injury
      (BBMI) in consecutive abdominal trauma. METHODS: This was a retrospective
      observational study of 805 consecutive abdominal traumas with 556 patients
      included and screened by an abdominal radiologist blinded to the patient outcome,
      to evaluate numerous CT findings and calculate their diagnostic performances.
      These CT findings were compared using univariate and multivariate analysis
      between patients who had a laparotomy-confirmed BBMI requiring surgical repair,
      and those without BBMI requiring surgery. A CT score was obtained with an
      internal bootstrap validation. RESULTS: Fifty-six patients (10.1 %) had BBMI
      requiring surgery. Nine CT signs were independently associated with BBMI
      requiring surgery and were used to develop a CT diagnostic score. The AUC of our
      model was 0.98 (95 % CI 0.96-100), with a >=5 cut-off. Its diagnostic performance
      was determined by internal validation: sensitivity 91.1-100 %, specificity 85.7
      97.6 %, positive predictive value 41.4-82.3 % and negative predictive value 98.9
      100 %. Bowel wall discontinuity and mesenteric pneumoperitoneum had the strongest
      association with BBMI requiring surgery (OR = 128.9 and 140.5, respectively).
      CONCLUSION: We developed a reliable CT scoring system which is easy to implement
      and highly predictive of BBMI requiring surgery. KEY POINTS: * Finding of bowel
      wall discontinuity or mesenteric pneumoperitoneum indicates BBMI requiring
      surgery. * Arterial mesenteric vessel extravasation requires surgery when in
      association with other CT findings. * Our CT scoring system has excellent
      diagnostic performance in predicting BBMI requiring surgery.

PMID- 25991478
TI  - Assessing hepatic fibrosis: comparing the intravoxel incoherent motion in MRI
      with acoustic radiation force impulse imaging in US.
AB  - OBJECTIVES: This study compared the diagnostic performance of intravoxel
      incoherent motion (IVIM) in magnetic resonance imaging (MRI) and acoustic
      radiation force impulse imaging (ARFI) in ultrasound (US) for liver fibrosis (LF)
      evaluation. METHODS: A total of 49 patients scheduled for liver surgery were
      recruited. LF in the non-tumorous liver parenchyma at the right lobe was
      estimated using a slow diffusion coefficient, fast diffusion coefficient (D
      fast), perfusion fraction (f) of the IVIM parameters, the total apparent
      diffusion coefficient of conventional diffusion-weighted imaging and the shear
      wave velocity (Vs) of ARFI. LF was graded using the Metavir scoring system on
      histological examination. The Spearman rank correlation coefficient for
      correlation and analysis of variance was used for determining difference. The
      diagnostic performance was compared using receiver operating characteristic curve
      analysis. RESULTS: LF exhibited significant correlation with the three parameters
      D fast, f, and Vs (r = -0.528, -0.337, and 0.481, respectively, P < 0.05). The D
      fast values in the F4 group were significantly lower than those in the F0, F1 and
      F2 groups. D fast exhibited a non-inferior performance for diagnosing all
      fibrosis grades compared with that of Vs. CONCLUSIONS: Both IVIM and ARFI provide
      reliable estimations for the noninvasive assessment of LF. KEY POINTS: * Liver
      fibrosis can be diagnosed and graded using noninvasive imaging modalities. * ARFI
      and IVIM can be incorporated into routine examinations. * IVIM can differentiate
      liver cirrhosis from none to moderate liver fibrosis. * The diagnostic
      performances of IVIM and ARFI are equal.

PMID- 25991479
TI  - Four-year cardiac magnetic resonance (CMR) follow-up of patients treated with
      percutaneous pulmonary valve stent implantation.
AB  - OBJECTIVES: To investigate follow-up after percutaneous pulmonary valve
      implantation (PPVI). METHODS: Forty patients with pulmonary conduit dysfunction
      (males/females 24/16; 21 +/- 08 years; 12 tetralogy of Fallot, 11 aortic valve
      disease, 17 other congenital heart disease) were planned for CMR before PPVI and
      repeated 7 times up to 48 months. CMR prospective results regarded: pressure
      gradient (PG) and regurgitation fraction (RF); end-diastolic volume, end-systolic
      volume, and stroke volume indexed to body surface area (EDVI, ESVI, and SVI);
      ejection fraction (EF) of right and left ventricles (RV, LV). A Friedman test was
      used for comparisons. RESULTS: Overall, PG (31 +/- 06 to 16 +/- 4 mmHg), RF (16
      +/- 17 to 0.3 +/- 1 %), RVEDVI (82 +/- 38 to 58 +/- 12 ml/m(2)), and RVESVI (44
      +/- 12 to 30 +/- 13 ml/m(2)) declined (p < 0.001), RVEF (49 +/- 13 to 58 +/- 12
      %) and RVSVI (from 38 +/- 14 to 40 +/- 8 ml/m(2)) increased (p < 0.001), LVEDVI
      (67 +/- 17 to 73 +/- 18 ml/m(2)) and LVSVI (37 +/- 11 to 43 +/- 10 ml/m(2))
      increased (p = 0.034 and p < 0.001). Two patients had valve fracture at 24 and 36
      months and underwent surgery. One patient had stent restenosis at 24 months and
      underwent percutaneous retreatment. Baseline/follow-up CMR did not predict PPVI
      failure. CONCLUSIONS: CMR demonstrated restored pulmonary conduit function,
      reduced RV volumes and increased RV and LV function but did not predict valve
      fracture/restenosis. KEY POINTS: * A CMR 4-year follow-up after PPVI showed
      restored pulmonary conduit function * RV volumes were significantly reduced * RV
      function was significantly better in terms of increased EF and SVI * LV function
      was significantly better in terms of increased EDVI and SVI * Baseline/follow-up
      CMR did not predict three cases of PPVI failure.

PMID- 25991480
TI  - Cystic form of paraduodenal pancreatitis (cystic dystrophy in heterotopic
      pancreas (CDHP)): a potential link with minor papilla abnormalities? A study in a
      large series.
AB  - OBJECTIVES: To analyze the association between cystic dystrophy in the
      heterotopic pancreas (CDHP) and minor papilla abnormalities. MATERIAL AND
      METHODS: Seventy-six patients with CDHP were retrospectively included over 14
      years. Two radiologists searched for MDCT signs of CDHP (cysts and thickened
      intestinal wall, inflammatory changes), and minor papilla abnormalities
      (Santorini duct dilatation, luminal calcifications of the minor papilla). Other
      pancreatic abnormalities (parenchymal calcifications, main pancreatic duct
      dilatation) or bile duct dilatation were also analysed. RESULTS: CDHP was mostly
      located in the second part of the duodenum (71/76, 93.5 %). Median duodenal wall
      thickness was 20 mm (range 10-46). There were multiple cysts in 86 % (65/76,
      median = 3), measuring 2-60 mm. No cysts were identified in four patients (5 %).
      Inflammatory changes were found in 87 % (66/76). Minor papilla abnormalities were
      found in 37 % (28/76) and calcifications in the minor papilla without
      calcifications in the major papilla were only observed in three patients (4 %).
      Abnormalities of the pancreas and main bile duct dilatation were identified in 78
      % (59/76) and 38 % (29/76). CONCLUSION: Previously described CT features were
      seen in most patients with CDHP. However, minor papilla abnormalities were seen
      in a minority of patients and, therefore, do not seem to be a predisposing factor
      for CDHP. KEY POINTS: Imaging features suggesting a CDHP diagnosis are confirmed
      in a large series. Minor papilla abnormalities do not seem to be a predisposing
      factor for CDHP. Most patients did not have any isolated minor papilla
      abnormalities.

PMID- 25991481
TI  - High resolution pituitary gland MRI at 7.0 tesla: a clinical evaluation in
      Cushing's disease.
AB  - OBJECTIVE: To evaluate the detection of pituitary lesions at 7.0 T compared to
      1.5 T MRI in 16 patients with clinically and biochemically proven Cushing's
      disease. METHODS: In seven patients, no lesion was detected on the initial 1.5 T
      MRI, and in nine patients it was uncertain whether there was a lesion. Firstly,
      two readers assessed both 1.5 T and 7.0 T MRI examinations unpaired in a random
      order for the presence of lesions. Consensus reading with a third
      neuroradiologist was used to define final lesions in all MRIs. Secondly, surgical
      outcome was evaluated. A comparison was made between the lesions visualized with
      MRI and the lesions found during surgery in 9/16 patients. RESULTS: The
      interobserver agreement for lesion detection was good at 1.5 T MRI (kappa = 0.69)
      and 7.0 T MRI (kappa = 0.62). In five patients, both the 1.5 T and 7.0 T MRI
      enabled visualization of a lesion on the correct side of the pituitary gland. In
      three patients, 7.0 T MRI detected a lesion on the correct side of the pituitary
      gland, while no lesion was visible at 1.5 T MRI. CONCLUSION: The interobserver
      agreement of image assessment for 7.0 T MRI in patients with Cushing's disease
      was good, and lesions were detected more accurately with 7.0 T MRI. KEY POINTS:
      Interobserver agreement for lesion detection on 1.5 T MRI was good; Interobserver
      agreement for lesion detection on 7.0 T MRI was good; 7.0 T enabled confirmation
      of unclear lesions at 1.5 T; 7.0 T enabled visualization of lesions not visible
      at 1.5 T.

PMID- 25991482
TI  - Humidifier disinfectant-associated children's interstitial lung disease: Computed
      tomographic features, histopathologic correlation and comparison between
      survivors and non-survivors.
AB  - OBJECTIVES: To report radiologic findings with histopathologic correlations of
      humidifier disinfectant-associated children's interstitial lung disease (HD
      chILD) and to compare computed tomography (CT) findings between survivors and non
      survivors. METHODS: Forty-seven children with HD-chILD (27.4 +/- 12.4 months old)
      were categorized as survivors (n = 25) and non-survivors (n = 22). The patterns,
      distributions, and chronological changes in lung lesions at follow-up CT were
      investigated. Histopathologic correlations were performed in 23 patients.
      RESULTS: CT features were characterized by chronological changes, from
      consolidation to centrilobular opacities, and lesions eventually became faint
      centrilobular nodules. Histopathologic features were bronchocentric-distributed
      fibro-inflammatory lesions, which were more profound in the advanced stage than
      the early stage. Consolidation >= 30 % [hazard ratio (HR), 2.932], centrilobular
      opacities >= 60 % of the total lung volume (TLV; HR, 0.206) and spontaneous air
      leaks (HR, 3.457) were significant factors associated with patient survival, as
      per univariate analysis. Consolidation >= 30 % (HR, 3.519), centrilobular
      opacities >= 60 % (HR, 0.205) and diffuse ground glass opacity (GGO) >= 70 % of
      the TLV (HR, 3.521) were significant factors associated with patient survival, as
      determined via multivariate analysis. CONCLUSION: Distinctive chronological CT
      features were observed in the HD-chILD images. Spontaneous air leaks,
      consolidation, GGO, and centrilobular opacities were prognostic factors. KEY
      POINTS: Chemical disinfectants can induce severe inhalation lung injury. Lung
      injury caused by inhaled disinfectants demonstrates chronologic changes in
      radiologic findings. Understanding of radiological characteristics is important
      to predict outcomes in chemical pneumonitis. Physicians should be aware of the
      potential risk of environmental chemicals.

PMID- 25991483
TI  - CT fluoroscopy-guided preoperative short hook wire placement for small pulmonary
      lesions: evaluation of safety and identification of risk factors for
      pneumothorax.
AB  - OBJECTIVES: To retrospectively evaluate the safety of computed tomography (CT)
      fluoroscopy-guided short hook wire placement for video-assisted thoracoscopic
      surgery and the risk factors for pneumothorax associated with this procedure.
      METHODS: We analyzed 267 short hook wire placements for 267 pulmonary lesions
      (mean diameter, 9.9 mm). Multiple variables related to the patients, lesions, and
      procedures were assessed to determine the risk factors for pneumothorax. RESULTS:
      Complications (219 grade 1 and 4 grade 2 adverse events) occurred in 196
      procedures. No grade 3 or above adverse events were observed. Univariate analysis
      revealed increased vital capacity (odds ratio [OR], 1.518; P = 0.021), lower lobe
      lesion (OR, 2.343; P =0.001), solid lesion (OR, 1.845; P = 0.014), prone
      positioning (OR, 1.793; P = 0.021), transfissural approach (OR, 11.941; P =
      0.017), and longer procedure time (OR, 1.036; P = 0.038) were significant
      predictors of pneumothorax. Multivariate analysis revealed only the transfissural
      approach (OR, 12.171; P = 0.018) and a longer procedure time (OR, 1.048; P =
      0.012) as significant independent predictors. CONCLUSION: Complications related
      to CT fluoroscopy-guided preoperative short hook wire placement often occurred,
      but all complications were minor. A transfissural approach and longer procedure
      time were significant independent predictors of pneumothorax. KEY POINTS:
      Complications related to CT fluoroscopy-guided preoperative short hook wire
      placement often occur. Complications are usually minor and asymptomatic. A
      transfissural approach and longer procedure time are significant independent
      predictors of pneumothorax.

PMID- 25991484
TI  - Effects of automatic tube potential selection on radiation dose index, image
      quality, and lesion detectability in pediatric abdominopelvic CT and CTA: a
      phantom study.
AB  - OBJECTIVES: To assess the effect of automatic tube potential selection (ATPS) on
      radiation dose, image quality, and lesion detectability in paediatric
      abdominopelvic CT and CT angiography (CTA). METHODS: A paediatric modular phantom
      with contrast inserts was examined with routine pitch (1.4) and high pitch (3.0)
      using a standard abdominopelvic protocol with fixed 120 kVp, and ATPS with
      variable kVp in non-contrast, contrast-enhanced, and CTA mode. The volume CT dose
      index (CTDIvol), contrast-to-noise ratio (CNR) and lesion detectability index
      (d') were compared between the standard protocol and ATPS examinations. RESULTS:
      CTDIvol was reduced in all routine pitch ATPS examinations, with dose reductions
      of 27-52 % in CTA mode (P < 0.0001), 15-33 % in contrast-enhanced mode (P =
      0.0003) and 8-14 % in non-contrast mode (P = 0.03). Iodine and soft tissue insert
      CNR and d' were improved or maintained in all ATPS examinations. kVp and dose
      were reduced in 25 % of high pitch ATPS examinations and in none of the full
      phantom examinations obtained after a single full phantom localizer. CONCLUSIONS:
      ATPS reduces radiation dose while maintaining image quality and lesion
      detectability in routine pitch paediatric abdominopelvic CT and CTA, but
      technical factors such as pitch and imaging range must be considered to optimize
      ATPS benefits. KEY POINTS: ATPS automatically individualizes CT scan technique
      for each patient. ATPS lowers radiation dose in routine pitch pediatric
      abdominopelvic CT and CTA. There is no loss of image quality or lesion
      detectability with ATPS. Pitch and scan range impact the effectiveness of ATPS
      dose reduction.

PMID- 25991485
TI  - Parametric response mapping of dynamic CT for predicting intrahepatic recurrence
      of hepatocellular carcinoma after conventional transcatheter arterial
      chemoembolization.
AB  - OBJECTIVES: The aim of our study was to determine the diagnostic value of a novel
      image analysis method called parametric response mapping (PRM) for prediction of
      intrahepatic recurrence of hepatocellular carcinoma (HCC) treated with
      conventional transcatheter arterial chemoembolization (TACE). METHODS: This
      retrospective study was approved by the IRB. We recruited 55 HCC patients who
      achieved complete remission (CR) after TACE and received longitudinal multiphasic
      liver computed tomography (CT). The patients fell into two groups: the recurrent
      tumour group (n = 29) and the non-recurrent tumour group (n = 26). We applied the
      PRM analysis to see if this technique could distinguish between the two groups.
      The results of the PRM analysis were incorporated into a prediction algorithm. We
      retrospectively removed data from the last time point and attempted to predict
      the response to therapy of the removed data. RESULTS: The PRM analysis was able
      to distinguish between the non-recurrent and recurrent groups successfully. The
      prediction algorithm detected response to therapy with an area under the curve
      (AUC) of 0.76, while the manual approach had AUC 0.64. CONCLUSIONS: Adopting PRM
      analysis can potentially distinguish between recurrent and non-recurrent HCCs and
      allow for prediction of response to therapy after TACE. KEY POINTS: Parametric
      response mapping (PRM) could help assess patients with recurrent HCCs after TACE.
      Parametric response mapping could direct patients to individualized therapy.
      Longitudinal CT images were analyzed with advanced image analysis method.

PMID- 25991486
TI  - CT evaluation of sigmoid plate dehiscence causing pulsatile tinnitus.
AB  - OBJECTIVES: To evaluate the characteristics of sigmoid plate dehiscence (SPD)
      causing pulsatile tinnitus (PT) on CT arteriography and venography (CTA + V).
      METHODS: Thirty PT patients treated successfully with SPD reconstruction were
      enrolled. Sixty asymptomatic patients were matched. The location, extent, number
      of SPD cases and concomitant signs, including venous outflow dominance,
      transverse sinus stenosis, high jugular bulb, temporal bone pneumatization,
      height of pituitary gland and pituitary fossa, abnormal mastoid emissary vein,
      were detected and compared using CTA + V. RESULTS: More than one SPD was found on
      the symptomatic side in 13/30 PT patients (43.3 %). The upper segment of the
      sigmoid plate was involved in 29/44 SPDs in the vertical direction (65.9 %); the
      lateral wall was involved in 38/44 SPDs in the horizontal direction (86.4 %).
      Singular SPD was detected in 3/60 asymptomatic patients (1.67 +/- 0.35 mm(2)),
      less so in PT patients (7.97 +/- 5.17 mm(2)). Compared with the control group,
      ipsilateral venous outflow dominance, high jugular bulb and bilateral transverse
      sinus stenosis were more common in the PT group, together with deeper pituitary
      fossa and flatter pituitary glands. CONCLUSION: SPD causing PT has characteristic
      CT findings. It may be generated by vascular or intracranial pressure
      abnormalities and act as a common key to triggering PT's perception. KEY POINTS:
      Pulsatile tinnitus (PT) caused by sigmoid plate dehiscence (SPD) may be cured.
      SPD causing PT has some characteristic findings on CT. SPD may be a common key to
      triggering PT's perception. Thin-slice high resolution CT venography is
      recommended for SPD assessment. The relationship between intracranial pressure
      and SPD causing PT should be studied.

PMID- 25991487
TI  - Accuracy and feasibility of estimated tumour volumetry in primary gastric
      gastrointestinal stromal tumours: validation using semiautomated technique in 127
      patients.
AB  - OBJECTIVES: To validate estimated tumour volumetry in primary gastric
      gastrointestinal stromal tumours (GISTs) using semiautomated volumetry. METHODS:
      In this IRB-approved retrospective study, we measured the three longest diameters
      in x, y, z axes on CTs of primary gastric GISTs in 127 consecutive patients (52
      women, 75 men, mean age 61 years) at our institute between 2000 and 2013.
      Segmented volumes (Vsegmented) were obtained using commercial software by two
      radiologists. Estimate volumes (V1-V6) were obtained using formulae for spheres
      and ellipsoids. Intra- and interobserver agreement of Vsegmented and agreement of
      V1-6 with Vsegmented were analysed with concordance correlation coefficients
      (CCC) and Bland-Altman plots. RESULTS: Median Vsegmented and V1-V6 were 75.9,
      124.9, 111.6, 94.0, 94.4, 61.7 and 80.3 cm(3), respectively. There was strong
      intra- and interobserver agreement for Vsegmented. Agreement with Vsegmented was
      highest for V6 (scalene ellipsoid, x ? y ? z), with CCC of 0.96 [95 % CI 0.95
      0.97]. Mean relative difference was smallest for V6 (0.6 %), while it was -19.1 %
      for V5, +14.5 % for V4, +17.9 % for V3, +32.6 % for V2 and +47 % for V1.
      CONCLUSION: Ellipsoidal approximations of volume using three measured axes may be
      used to closely estimate Vsegmented when semiautomated techniques are
      unavailable. KEY POINTS: Estimation of tumour volume in primary GIST using
      mathematical formulae is feasible. Gastric GISTs are rarely spherical. Segmented
      volumes are highly concordant with three axis-based scalene ellipsoid volumes.
      Ellipsoid volume can be used as an alternative for automated tumour volumetry.

PMID- 25991488
TI  - The diagnostic efficacy of quantitative liver MR imaging with diffusion-weighted,
      SWI, and hepato-specific contrast-enhanced sequences in staging liver fibrosis--a
      multiparametric approach.
AB  - PURPOSE: To assess the diagnostic efficacy of multiparametric MRI using
      quantitative measurements of the apparent diffusion coefficient (ADC) of the
      liver parenchyma on diffusion-weighted imaging (DWI), signal intensity (SI) on
      susceptibility-weighted imaging (SWI), and gadoxetic acid-enhanced T1-weighted
      imaging during the hepatobiliary phase for the staging of liver fibrosis.
      MATERIALS AND METHODS: Seventy-seven patients underwent a 3T MRI examination,
      including DWI/SWI sequences and gadoxetic acid-enhanced T1-weighted MRI. Liver
      fibrosis according to liver biopsy was staged using the Metavir fibrosis score:
      F0 (n = 21, 27.3%); F1 (n = 7, 9.1%); F2 (n = 8, 10.4%); F3 (n = 12, 15.6%); and
      F4 (n = 29, 37.7%). SI of the liver was defined using region-of-interest
      measurements to calculate the ADC values, the relative enhancement (RE) in the
      hepatobiliary phase, and the liver-to-muscle ratio (LMR) measurements for SWI.
      RESULTS: The values of RE, LMR, and ADC measurements were statistically
      significantly different among the five fibrosis stages (p < 0.004). Combining the
      three parameters in a multiparametric approach, the AUC for detecting F1 stage or
      greater (>= F1) was 94%, for F2 or greater (>=F2) was 95%, for F3 or greater
      (>=F3) was 90%, and for stage F4 was 93%. CONCLUSIONS: Multiparametric MRI is an
      efficient non-invasive diagnostic tool for the staging of liver fibrosis. KEY
      POINTS: * Multiparametric MRI has high accuracy in predicting moderate or greater
      liver fibrosis. * Relative enhancement post- gadoxetic acid is an independent
      predictor of liver fibrosis. * Liver SWI signal intensity and ADC values enhance
      the diagnostic ability.

PMID- 25991489
TI  - Diagnostic accuracy and utility of coronary CT angiography with consideration of
      unevaluable results: A systematic review and multivariate Bayesian random-effects
      meta-analysis with intention to diagnose.
AB  - OBJECTIVES: To meta-analyze diagnostic accuracy, test yield and utility of
      coronary computed tomography angiography (CCTA) in coronary artery disease (CAD)
      by an intention-to-diagnose approach with inclusion of unevaluable results.
      METHODS: Four databases were searched from 1/2005 to 3/2013 for prospective
      studies that used 16-320-row or dual-source CTs and provided 3 * 2 patient-level
      data of CCTA (positive, negative, or unevaluable) versus catheter angiography
      (positive or negative) for diagnosing >=50% coronary stenoses. A Bayesian
      multivariate 3 * 2 random-effects meta-analysis considered unevaluable CCTAs.
      RESULTS: Thirty studies (3422 patients) were included. Compared to 16-40 row CT,
      test yield and accuracy of CCTA has significantly increased with >=64-row CT (P <
      0.05). In >=64-row CT, about 2.5% (95%-CI, 0.9-4.8%) of diseased patients and
      7.5% (4.5-11.2%) of non-diseased patients had unevaluable CCTAs. A positive
      likelihood ratio of 8.9 (6.1-13.5) indicated moderate suitability for identifying
      CAD. A negative likelihood ratio of 0.022 (0.01-0.04) indicated excellent
      suitability for excluding CAD. Unevaluable CCTAs had an equivocal likelihood
      ratio of 0.42 (0.22-0.71). In the utility analysis, CCTA was useful at
      intermediate pre-test probabilities (16-70%). CONCLUSIONS: CCTA is useful at
      intermediate CAD pre-test probabilities. Positive CCTAs require verification to
      confirm CAD, unevaluable CCTAs require alternative diagnostics, and negative
      CCTAs exclude obstructive CAD with high certainty. KEY POINTS: * This 3 * 2
      Bayesian meta-analysis included unevaluable CCTAs with intention-to-diagnose. *
      CCTA is currently useful at intermediate CAD pre-test probabilities. *
      Unevaluable CCTAs should not, generally, be treated as if they are positive. *
      Positive CCTAs require verification by other methods to confirm CAD. * Negative
      CCTAs exclude CAD with high certainty.

PMID- 25991490
TI  - Novel penalised likelihood reconstruction of PET in the assessment of
      histologically verified small pulmonary nodules.
AB  - OBJECTIVES: Investigate the effect of a novel Bayesian penalised likelihood (BPL)
      reconstruction algorithm on analysis of pulmonary nodules examined with 18F-FDG
      PET/CT, and to determine its effect on small, sub-10-mm nodules. METHODS: 18F-FDG
      PET/CTs performed for nodule evaluation in 104 patients (121 nodules) were
      retrospectively reconstructed using the new algorithm, and compared to time-of
      flight ordered subset expectation maximisation (OSEM) reconstruction. Nodule and
      background parameters were analysed semi-quantitatively and visually. RESULTS:
      BPL compared to OSEM resulted in statistically significant increases in nodule
      SUVmax (mean 5.3 to 8.1, p < 0.00001), signal-to-background (mean 3.6 to 5.3, p <
      0.00001) and signal-to-noise (mean 24 to 41, p < 0.00001). Mean percentage
      increase in SUVmax (%DeltaSUVmax) was significantly higher in nodules <=10 mm (n
      = 31, mean 73%) compared to >10 mm (n = 90, mean 42 %) (p = 0.025). Increase in
      signal-to-noise was higher in nodules <=10 mm (224%, mean 12 to 27) compared to
      >10 mm (165%, mean 28 to 46). When applying optimum SUVmax thresholds for
      detecting malignancy, the sensitivity and accuracy increased using BPL, with the
      greatest improvements in nodules <=10 mm. CONCLUSION: BPL results in a
      significant increase in signal-to-background and signal-to-noise compared to
      OSEM. When semi-quantitative analyses to diagnose malignancy are applied, higher
      SUVmax thresholds may be warranted owing to the SUVmax increase compared to OSEM.
      KEY POINTS: * Novel Bayesian penalised likelihood PET reconstruction was applied
      for lung nodule evaluation. * This was compared to current standard of care OSEM
      reconstruction. * The novel reconstruction generated significant increases in
      lung nodule signal-to-background and signal-to-noise. * These increases were
      highest in small, sub-10-mm pulmonary nodules. * Higher SUV max thresholds may be
      warranted when using semi-quantitative analyses to diagnose malignancy.

PMID- 25991491
TI  - Effects of solvent polarity on the absorption and fluorescence spectra of
      chlorogenic acid and caffeic acid compounds: determination of the dipole moments.
AB  - The effects of solvent polarity on absorption and fluorescence spectra of
      biologically active compounds (chlorogenic acid (CGA) and caffeic acids (CA))
      have been investigated. In both spectra pronounced solvatochromic effects were
      observed with shift of emission peaks larger than the corresponding UV-vis
      electronic absorption spectra. From solvatochromic theory the ground and excited
      state dipole moments were determined experimentally and theoretically. The
      differences between the excited and ground state dipole moment determined by
      Bakhshiev, Kawski-Chamma-Viallet and Reichardt equations are quite similar. The
      ground and excited-state dipole moments were determined by theoretical quantum
      chemical calculation using density function theory (DFT) method (Gaussian 09) and
      were also similar to the experimental results. The HOMO-LUMO energy band gaps for
      CGA and CFA were calculated and found to be 4.1119 and 1.8732 eV respectively.
      The results also indicated the CGA molecule is more stable than that of CFA. It
      was also observed that in both compounds the excited state possesses a higher
      dipole moment than that of the ground state. This confirms that the excited state
      of the hydroxycinnamic compounds is more polarized than that of the ground state
      and therefore is more sensitive to the solvent.

PMID- 25991492
TI  - [Budesonide foam for ulcerative proctitis and proctosigmoiditis].

PMID- 25991493
TI  - Conjugated microporous polymers with dimensionality-controlled heterostructures
      for green energy devices.
AB  - Dimensionality for conjugated micro-porous polymers (CMP-nD, n = 0, 1, 2) is
      proven to be of great importance for tailoring their photophysical properties.
      Moreover, CMP-nD can further be converted into boron and nitrogen co-doped porous
      carbons (nDBN, n = 0, 1, 2) with maintained 0D, 1D, and 2D nano-structures and
      highly efficient catalytic performance. 

PMID- 25991494
TI  - The incidence and location of prostatic calculi on noncontrast computed
      tomography images in patients with renal calculi.
AB  - In this study, the incidence and location of prostatic calculi on noncontrast
      abdominal computed tomography (NCACT) images of patients with and without renal
      stones were investigated. Between 2006 and 2013, NCACT images were taken of 133
      patients treated for renal stones (Group I) and of 100 age-matched control
      patients with putative urinary stone disease (Group II) in our clinic. The
      incidence and location of prostatic calculi on these images were determined. The
      location of prostatic calculus was classified as type A if they were located in
      the main prostatic ducts, and type B if they were located outside the ducts.
      Prostatic calculi were present in 44.4% of patients in Group I and 21.0% of
      patients in Group II. The incidence of prostatic calculi was significantly higher
      in patients with urinary stones compared with those without (P<0.001). The
      location of prostatic calculi in Group I included 74.6% type A and 25.4% type B
      while in Group II the locations were 76.2% type A and 23.8% type B. The incidence
      of prostatic calculi is more prevalent in patients with renal stones. On NCACT
      images, prostatic calculi were mostly detected in the main prostatic ducts, which
      were defined as type A.

PMID- 25991496
TI  - 55th annual teratology society meeting.

PMID- 25991495
TI  - Views of practice managers and general practitioners on implementing NHS Health
      Checks.
AB  - As part of an evaluation of a contract with general practices to deliver the
      national NHS Health Checks programme in Sefton, North West England, we surveyed
      general practitioners (GPs) and practice managers (PMs) in all 55 practices. The
      contract required practices to identify individuals from their practice registers
      with potentially high cardiovascular disease risk, and provide annual reviews.
      Responses were obtained from 43/178 GPs and 40/55 PMs representing 56 and 73% of
      practices, respectively. There was variation in many aspects of implementation.
      Time and software were viewed as barriers to implementation, the increased nurse
      workload impacted on other services and payments were insufficient to cover
      costs. The main enabler for successful implementation was IT support. Fewer than
      half the respondents viewed the programme as beneficial to their practice.
      Findings have been used to address many issues raised. Practices need more
      support from commissioners to help implement NHS Health Checks. 

PMID- 25991498
TI  - Fate and proliferation of typical antibiotic resistance genes in five full-scale
      pharmaceutical wastewater treatment plants.
AB  - This study investigated the characteristics of 10 subtypes of antibiotic
      resistance genes (ARGs) for sulfonamide, tetracycline, beta-lactam and macrolide
      resistance and the class 1 integrase gene (intI1). In total, these genes were
      monitored in 24 samples across each stage of five full-scale pharmaceutical
      wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative
      polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the
      final effluents ranged from (2.08+/-0.16)*10(3) to (3.68+/-0.27)*10(6) copies/mL.
      The absolute abundance of ARGs in effluents accounted for only 0.6%-59.8% of
      influents of the five PWWTPs, while the majority of the ARGs were transported to
      the dewatered sludge with concentrations from (9.38+/-0.73)*10(7) to (4.30+/
      0.81)*10(10) copies/g dryweight (dw). The total loads of ARGs discharged through
      dewatered sludge was 7-308 folds higher than that in the raw influents and 16-638
      folds higher than that in the final effluents. The proliferation of ARGs mainly
      occurs in the biological treatment processes, such as conventional activated
      sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR),
      implying that significant replication of certain subtypes of ARGs may be
      attributable to microbial growth. High concentrations of antibiotic residues
      (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected
      wastewater treatment systems and they still remain high residues in the
      effluents. Partial correlation analysis showed significant correlations between
      the antibiotic concentrations and the associated relative abundance of ARG
      subtypes in the effluent. Although correlation does not prove causation, this
      study demonstrates that in addition to bacterial growth, the high antibiotic
      residues within the pharmaceutical WWTPs may influence the proliferation and fate
      of the associated ARG subtypes.

PMID- 25991500
TI  - Impact of thymine glycol damage on DNA duplex energetics: Correlations with
      lesion-induced biochemical and structural consequences.
AB  - The magnitude and nature of lesion-induced energetic perturbations empirically
      correlate with mutagenicity/cytotoxicity profiles and can be predictive of lesion
      outcomes during polymerase-mediated replication in vitro. In this study, we
      assess the sequence and counterbase-dependent energetic impact of the Thymine
      glycol (Tg) lesion on a family of deoxyoligonucleotide duplexes. Tg damage arises
      from thymine and methyl-cytosine exposure to oxidizing agents or radiation
      generated free-radicals. The Tg lesion blocks polymerase-mediated DNA replication
      in vitro and the unrepaired site elicits cytotoxic lethal consequences in vivo.
      Our combined calorimetric and spectroscopic characterization correlates Tg 
      induced energetic perturbations with biological and structural properties.
      Specifically, we incorporate a 5R-Tg isomer centered within the tridecanucleotide
      sequence 5'-GCGTACXCATGCG-3' (X = Tg or T) which is hybridized with the
      corresponding complementary sequence 5'-CGCATGNGTACGC-3' (N = A, G, T, C) to
      generate families of Tg -damaged (Tg .N) and lesion-free (T.N) duplexes. We
      demonstrate that the magnitude and nature of the Tg destabilizing impact is
      dependent on counterbase identity (i.e., A ~ G < T < C). The observation that a
      Tg lesion is less destabilizing when positioned opposite purines suggests that
      favorable counterbase stacking interactions may partially compensate lesion
      induced perturbations. Moreover, the destabilizing energies of Tg .N duplexes
      parallel their respective lesion-free T.N mismatch counterparts (i.e., G < T <
      C). Elucidation of Tg-induced destabilization relative to the corresponding
      undamaged mismatch energetics allows resolution of lesion-specific and sequence
      dependent impacts. The Tg-induced energetic perturbations are consistent with its
      replication blocking properties and may serve as differential recognition
      elements for discrimination by the cellular repair machinery.

PMID- 25991499
TI  - The art of targeting gut microbiota for tackling human obesity.
AB  - Recently, a great deal of interest has been expressed regarding strategies to
      tackle worldwide obesity because of its accelerated wide spread accompanied with
      numerous negative effects on health and high costs. Obesity has been
      traditionally associated with an imbalance in energy consumed when compared to
      energy expenditure. However, growing evidence suggests a less simplistic event in
      which gut microbiota plays a key role. Obesity, in terms of microbiota, is a
      complicated disequilibrium that presents many unclear complications. Despite
      this, there is special interest in characterizing compositionally and
      functionally the obese gut microbiota with the help of in vitro, animal and human
      studies. Considering the gut microbiota as a factor contributing to human obesity
      represents a tool of great therapeutic potential. This paper reviews the use of
      antimicrobials, probiotics, fecal microbial therapy, prebiotics and diet to
      manipulate obesity through the human gut microbiota and reveals inconsistencies
      and implications for future study. 

PMID- 25991501
TI  - SOCIO-ETHICAL ISSUES IN PERSONALIZED MEDICINE: A SYSTEMATIC REVIEW OF ENGLISH
      LANGUAGE HEALTH TECHNOLOGY ASSESSMENTS OF GENE EXPRESSION PROFILING TESTS FOR
      BREAST CANCER PROGNOSIS.
AB  - OBJECTIVES: There have been multiple calls for explicit integration of ethical,
      legal, and social issues (ELSI) in health technology assessment (HTA) and
      addressing ELSI has been highlighted as key in optimizing benefits in the
      Omics/Personalized Medicine field. This study examines HTAs of an early clinical
      example of Personalized Medicine (gene expression profile tests [GEP] for breast
      cancer prognosis) aiming to: (i) identify ELSI; (ii) assess whether ELSIs are
      implicitly or explicitly addressed; and (iii) report methodology used for ELSI
      integration. METHODS: A systematic search for HTAs (January 2004 to September
      2012), followed by descriptive and qualitative content analysis. RESULTS:
      Seventeen HTAs for GEP were retrieved. Only three (18%) explicitly presented
      ELSI, and only one reported methodology. However, all of the HTAs included
      implicit ELSI. Eight themes of implicit and explicit ELSI were identified.
      "Classical" ELSI including privacy, informed consent, and concerns about limited
      patient/clinician genetic literacy were always presented explicitly. Some ELSI,
      including the need to understand how individual patients' risk tolerances affect
      clinical decision-making after reception of GEP results, were presented both
      explicitly and implicitly in HTAs. Others, such as concern about evidentiary
      deficiencies for clinical utility of GEP tests, occurred only implicitly.
      CONCLUSIONS: Despite a wide variety of important ELSI raised, these were rarely
      explicitly addressed in HTAs. Explicit treatment would increase their
      accessibility to decision-makers, and may augment HTA efficiency maximizing their
      utility. This is particularly important where complex Personalized Medicine
      applications are rapidly expanding choices for patients, clinicians and
      healthcare systems.

PMID- 25991502
TI  - Statistical modeling to characterize relationships between knee anatomy and
      kinematics.
AB  - The mechanics of the knee are complex and dependent on the shape of the articular
      surfaces and their relative alignment. Insight into how anatomy relates to
      kinematics can establish biomechanical norms, support the diagnosis and treatment
      of various pathologies (e.g., patellar maltracking) and inform implant design.
      Prior studies have used correlations to identify anatomical measures related to
      specific motions. The objective of this study was to describe relationships
      between knee anatomy and tibiofemoral (TF) and patellofemoral (PF) kinematics
      using a statistical shape and function modeling approach. A principal component
      (PC) analysis was performed on a 20-specimen dataset consisting of shape of the
      bone and cartilage for the femur, tibia and patella derived from imaging and six
      degree-of-freedom TF and PF kinematics from cadaveric testing during a simulated
      squat. The PC modes characterized links between anatomy and kinematics; the first
      mode captured scaling and shape changes in the condylar radii and their influence
      on TF anterior-posterior translation, internal-external rotation, and the
      location of the femoral lowest point. Subsequent modes described relations in
      patella shape and alta/baja alignment impacting PF kinematics. The complex
      interactions described with the data-driven statistical approach provide insight
      into knee mechanics that is useful clinically and in implant design.

PMID- 25991503
TI  - Difficult Hypertension Clinic Utilizing a Nurse Specialist: A Cost-Efficient
      Model for the Modern Era?
AB  - In the modern era in New Zealand, there has been a lack of specialist
      hypertension clinics where family practitioners might refer patients with
      difficult-to-treat or resistant hypertension. A new specialist referral
      hypertension clinic was established in 2009 at North Shore Hospital, Auckland,
      employing a model of care where much of the follow-up work is done by a nurse
      specialist. The authors review data from the first 1000 patients discharged from
      the clinic. Mean (treated) blood pressure improved by -26/12 mm Hg over an
      average of three visits, two thirds of which were to nurse specialist clinics.
      The authors propose this as a cost-efficient model that could easily be
      duplicated in other centers. 

PMID- 25991504
TI  - BAX and BCL-2 polymorphisms, as predictors of proliferative vitreoretinopathy
      development in patients suffering retinal detachment: the Retina 4 project.
AB  - PURPOSE: To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A
      (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal
      detachment (RRD) surgery in relation to the further development of proliferative
      vitreoretinopathy (PVR). METHODS: A case-control gene association study, as a
      part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms
      were analysed in 555 samples from patients with RRD (134 with PVR secondary to
      surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX
      polymorphisms between subsamples were analysed in two phases. Genotypic and
      allelic frequencies were compared in global sample and in subsamples. RESULTS:
      BAX: Differences were observed in the genotype frequencies and in AA carriers
      between controls and cases in the global series. The odds ratio (OR) of A
      carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of
      genotypes in Spain + Portugal were significant different. The OR of A carriers
      from Spain and Portugal was 1.8 (95% CI: 1.11-2.95). BCL-2: No significant
      differences were observed in genotype frequencies. However, proportions of
      genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95%
      CI: 0.43-0.96) was found in A carriers from Spain and Portugal. CONCLUSIONS:
      Results suggest that A allele of rs4645878 could be a biomarker of high risk of
      developing PVR in patients undergoing RD surgery. The possible role of BCL-2
      (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis
      should be investigated.

PMID- 25991506
TI  - Enhancing the Relevance of Incident Management Systems in Public Health Emergency
      Preparedness: A Novel Conceptual Framework.
AB  - We outline a conceptual framework developed to meet the needs of public health
      professionals in the province of Ontario for incident management system-related
      education and training. By using visual models, this framework applies a public
      health lens to emergency management, introducing concepts relevant to public
      health and thereby shifting the focus of emergency preparedness from a strict
      "doctrine" to a more dynamic and flexible approach grounded in the traditional
      principles of incident management systems. These models provide a foundation for
      further exploration of the theoretical foundations for public health emergency
      preparedness in practice.

PMID- 25991505
TI  - Accuracy and precision of silicon based impression media for quantitative areal
      texture analysis.
AB  - Areal surface texture analysis is becoming widespread across a diverse range of
      applications, from engineering to ecology. In many studies silicon based
      impression media are used to replicate surfaces, and the fidelity of replication
      defines the quality of data collected. However, while different investigators
      have used different impression media, the fidelity of surface replication has not
      been subjected to quantitative analysis based on areal texture data. Here we
      present the results of an analysis of the accuracy and precision with which
      different silicon based impression media of varying composition and viscosity
      replicate rough and smooth surfaces. Both accuracy and precision vary greatly
      between different media. High viscosity media tested show very low accuracy and
      precision, and most other compounds showed either the same pattern, or low
      accuracy and high precision, or low precision and high accuracy. Of the media
      tested, mid viscosity President Jet Regular Body and low viscosity President Jet
      Light Body (Coltene Whaledent) are the only compounds to show high levels of
      accuracy and precision on both surface types. Our results show that data acquired
      from different impression media are not comparable, supporting calls for greater
      standardisation of methods in areal texture analysis. 

PMID- 25991507
TI  - Drug resistance in Mycobacterium leprae from patients with leprosy in China.
AB  - BACKGROUND: Previous studies of drug resistance have shown that mutations in the
      drug resistance-determining region (DRDR) in the Folp1, RpoB and GyrA genes of
      Mycobacterium leprae are responsible for resistance to dapsone, rifampin and
      ofloxacin, respectively. AIM: To investigate the prevalence of mutations in genes
      associated with drug resistance in M. leprae isolates from patients with leprosy
      in Shandong Province. METHODS: The DRDR in the FolP1, RpoB and GyrA genes was
      analysed by direct sequencing of the PCR product from 85 isolates of M. leprae
      sampled from patients with leprosy in Shandong, China. RESULTS: Sequencing
      results were obtained for FolP1, RpoB and GyrA in 67, 57 and 81 of the 85
      samples, with mutation rates of 1.5% (1/67), 8.8% 5/57 and 25.9% (21/81). Three
      multidrug-resistant samples were found among the new cases: one had a mutation in
      both Folp1 and RpoB, while the other two had a mutation in both RpoB and GyrA.
      CONCLUSIONS: Primary resistance appears to be to either single drugs or
      combinations of two drugs. The resistance rate to dapsone seems to be low. To our
      knowledge, this is the first case of multidrug-resistant M. leprae from China.

PMID- 25991508
TI  - Topological events in single molecules of E. coli DNA confined in nanochannels.
AB  - We present experimental data concerning potential topological events such as
      folds, internal backfolds, and/or knots within long molecules of double-stranded
      DNA when they are stretched by confinement in a nanochannel. Genomic DNA from E.
      coli was labeled near the 'GCTCTTC' sequence with a fluorescently labeled dUTP
      analog and stained with the DNA intercalator YOYO. Individual long molecules of
      DNA were then linearized and imaged using methods based on the NanoChannel Array
      technology (Irys(r) System) available from BioNano Genomics. Data were collected
      on 189 153 molecules of length greater than 50 kilobases. A custom code was
      developed to search for abnormal intensity spikes in the YOYO backbone profile
      along the length of individual molecules. By correlating the YOYO intensity
      spikes with the aligned barcode pattern to the reference, we were able to
      correlate the bright intensity regions of YOYO with abnormal stretching in the
      molecule, which suggests these events were either a knot or a region of internal
      backfolding within the DNA. We interpret the results of our experiments involving
      molecules exceeding 50 kilobases in the context of existing simulation data for
      relatively short DNA, typically several kilobases. The frequency of these events
      is lower than the predictions from simulations, while the size of the events is
      larger than simulation predictions and often exceeds the molecular weight of the
      simulated molecules. We also identified DNA molecules that exhibit large, single
      folds as they enter the nanochannels. Overall, topological events occur at a low
      frequency (~7% of all molecules) and pose an easily surmountable obstacle for the
      practice of genome mapping in nanochannels. 

PMID- 25991509
TI  - [Superolateral dislocation of the temporomadibular joint: Case report].
AB  - INTRODUCTION: Superolateral disclocations of the temporomandibular joint are
      rare. They mostly occur after high-energy trauma and are frequently associated
      with fractures of the mandibular body. CASE REPORT: A 35-year-old man was
      admitted for the management of a high-energy craniofacial trauma due to a road
      accident. The initial assessment revealed bilateral superolateral
      temporomandibular joint disclocations, with bilateral sagittal fractures of the
      condyle head and a fracture of the right parasymphysis. The treatment consisted
      in an external reduction of both condyles, followed by open reduction and
      internal fixation of the parasymphysis. The patient quickly started physiotherapy
      after the procedure and recovered a normal mouth opening after a month of follow
      up. DISCUSSION: For most authors, a quick management of superolateral
      dislocations is necessary in order to achieve a proper reduction of the
      temporomandibular joint dislocation and avoid surgical reduction.
      Temporomandibular joint ankylosis is the main complication of such lesions. Early
      physiotherapy is indicated in order to prevent ankylosis.

PMID- 25991511
TI  - Mesenchymal stromal cells and the acute respiratory distress syndrome (ARDS):
      challenges for clinical application.

PMID- 25991510
TI  - The small GTPase MoYpt7 is required for membrane fusion in autophagy and
      pathogenicity of Magnaporthe oryzae.
AB  - Rab GTPases are required for vesicle-vacuolar fusion during vacuolar biogenesis
      in fungi. To date, little is known about the biological functions of the Rab
      small GTPase components in Magnaporthe oryzae. In this study, we investigated
      MoYpt7 of M. oryzae, a homologue of the small Ras-like GTPase Ypt7 in
      Saccharomyces cerevisiae. Cellular localization assays showed that MoYpt7 was
      predominantly localized to vacuolar membranes. Using a targeted gene disruption
      strategy, a DeltaMoYPT7 mutant was generated that exhibited defects in mycelial
      growth and production of conidia. The conidia of the DeltaMoYPT7 mutant were
      malformed and defective in the formation of appressoria. Consequently, the
      DeltaMoYPT7 mutant failed to cause disease in rice and barley. Furthermore, the
      DeltaMoYPT7 mutant showed impairment in autophagy, breached cell wall integrity,
      and higher sensitivity to both calcium and heavy metal stress. Transformants
      constitutively expressing an active MoYPT7 allele (MoYPT7-CA, Gln67Leu) exhibited
      distinct phenotypes from the DeltaMoYPT7 mutant. Expression of MoYPT7-CA in
      MoYpt7 reduced pathogenicity and produced more appressoria-forming single-septum
      conidia. These results indicate that MoYPT7 is required for fungal morphogenesis,
      vacuole fusion, autophagy, stress resistance and pathogenicity in M. oryzae. 

PMID- 25991512
TI  - Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolated from Blood Samples
      and Antibiotic Utilization in a University Hospital in Japan.
AB  - INTRODUCTION: Pseudomonas aeruginosa is one of the most important causes of
      nosocomial infection. Several reports indicated a correlation of antimicrobial
      usages and declined susceptibilities. In this report, we evaluated their relation
      in a tertiary care teaching hospital in Tokyo, Japan for 4 years. METHODS: We
      evaluated the susceptibilities of 149 strains of P. aeruginosa isolated from
      blood samples and consumption of anti-pseudomonal antibiotics as antimicrobial
      use density from 2009 to 2012 in the University of Tokyo Hospital in Tokyo,
      Japan. RESULTS: Usages of carbapenems and anti-pseudomonal cephalosporins
      decreased 44% and 31% from 2009 to 2011, and then increased 30% and 24% in 2012,
      respectively. Usage of piperacillin-tazobactam increased 87% from 2009 to 2012,
      which was introduced in the hospital in 2008. Consumption of fluoroquinolones and
      aminoglycoside remained low in those years. Susceptibilities to cephalosporins,
      carbapenems (except for panipenem-betamipron), penicillins, and fluoroquinolones
      declined between 22% and 39% in 2010, increased in the range of 16-31% in 2011,
      and increased by 1-14% in 2012. Susceptibility of panipenem-betamipron ranged
      between 25% and 32%. Susceptibility to aminoglycoside was more than 90% during
      this period. No relationship between antimicrobial usages and susceptibilities of
      P. aeruginosa was observed. CONCLUSION: Susceptibilities of P. aeruginosa did not
      correlate with the usage of antibiotics in our hospital. Several infection
      control measures and other factors might contribute to changing the
      susceptibilities of bacteria.

PMID- 25991513
TI  - An impurity intermediate band due to Pb doping induced promising thermoelectric
      performance of Ca5In2Sb6.
AB  - Band engineering is one of the effective approaches for designing ideal
      thermoelectric materials. Introducing an intermediate band in the band gap of
      semiconducting thermoelectric compounds may largely increase the carrier
      concentration and improve the electrical conductivity of these compounds. We test
      this hypothesis by Pb doping in Zintl Ca5In2Sb6. In the current work, we have
      systematically investigated the electronic structure and thermoelectric
      performances of substitutional doping with Pb on In sites at a doping level of 5%
      (0.2 e per cell) for Ca5In2Sb6 by using density functional theory combined with
      semi-classical Boltzmann theory. It is found that in contrast to Zn doping, Pb
      doping introduces a partially filled intermediate band in the band gap of
      Ca5In2Sb6, which originates from the Pb s states by weakly hybridizing with the
      Sb p states. Such an intermediate band dramatically increases the electrical
      conductivity of Ca5In2Sb6 and has little detrimental effect on its Seebeck
      coefficient, which may increase its thermoelectric figure of merit, ZT.
      Interestingly, a maximum ZT value of 2.46 may be achieved at 900 K for
      crystalline Pb-doped Ca5In2Sb6 when the carrier concentration is optimized.
      Therefore, Pb-doped Ca5In2Sb6 may be a promising thermoelectric material. 

PMID- 25991514
TI  - Breast cancer incidence and menopausal hormone therapy in Norway from 2004 to
      2009: a register-based cohort study.
AB  - In Norway, the breast cancer incidence increased by 50% in the 1990 s, during a
      period with initiation of mammography screening as well as a fourfold increase in
      use of menopausal hormone therapy (HT). After 2002, the HT use has dropped
      substantially; however, the breast cancer incidence has declined only marginally.
      How much mammography screening contributed to the breast cancer incidence
      increase in the 1990 s compared with HT use and specifically different types of
      HT use, has thus been discussed. Whether HT affects the incidence of subtypes of
      breast cancer differently has also been questioned. We have linked individual
      data from several national registries from 2004 to 2009 on 449,717 women aged 50
      65 years. 4597 cases of invasive cancer and 681 cases of ductal carcinoma in situ
      (DCIS) were included in the analysis. We used Cox regression to estimate hazard
      ratio (HR) as a measure of the relative risk of breast cancer associated with use
      of HT. The HRs associated with prescriptions of HT for more than 1 year were 2.06
      (1.90-2.24) for estrogen and progesterone combinations, 1.03 (0.85-1.25) for
      systemic estrogens, and 1.23 (1.01-1.51) for tibolone. Invasive lobular carcinoma
      was more strongly associated with use of estrogen and progesterone combinations,
      HR = 3.10 (2.51-3.81), than nonlobular carcinoma, HR = 1.94 (1.78-2.12). The
      corresponding value for DCIS was 1.61 (1.28-2.02). We estimated the population
      attributable fraction to 8.2%, corresponding to 90 breast cancer cases in 2006
      indicating that HT use still caused a major number of breast cancer cases.

PMID- 25991520
TI  - Organofluorine chemistry: A Janus cyclohexane ring.

PMID- 25991521
TI  - Main group chemistry: Small silicon oxides isolated.

PMID- 25991522
TI  - Metal-organic frameworks: Shuttling in the solid state.

PMID- 25991523
TI  - Supramolecular polymers: Chain growth in control.

PMID- 25991524
TI  - Computational chemistry: Making a bad calculation.

PMID- 25991525
TI  - Orthogonal tandem catalysis.
AB  - Tandem catalysis is a growing field that is beginning to yield important
      scientific and technological advances toward new and more efficient catalytic
      processes. 'One-pot' tandem reactions, where multiple catalysts and reagents,
      combined in a single reaction vessel undergo a sequence of precisely staged
      catalytic steps, are highly attractive from the standpoint of reducing both waste
      and time. Orthogonal tandem catalysis is a subset of one-pot reactions in which
      more than one catalyst is used to promote two or more mechanistically distinct
      reaction steps. This Perspective summarizes and analyses some of the recent
      developments and successes in orthogonal tandem catalysis, with particular focus
      on recent strategies to address catalyst incompatibility. We also highlight the
      concept of thermodynamic leveraging by coupling multiple catalyst cycles to
      effect challenging transformations not observed in single-step processes, and to
      encourage application of this technique to energetically unfavourable or
      demanding reactions. 

PMID- 25991526
TI  - All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane.
AB  - The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which
      all of the fluorines are 'up', is prepared in a 12-step protocol. The molecule
      adopts a classic chair conformation with alternate C-F bonds aligned triaxially,
      clustering three highly electronegative fluorine atoms in close proximity. This
      generates a cyclohexane with a high molecular dipole (MU = 6.2 D), unusual in an
      otherwise aliphatic compound. X-ray analysis indicates that the intramolecular
      Fax...Fax distances (~2.77 A) are longer than the vicinal Fax...Feq- distances
      (~2.73 A) suggesting a tension stabilizing the chair conformation. In the solid
      state the molecules pack in an orientation consistent with electrostatic
      ordering. Our synthesis of this highest-energy isomer demonstrates the properties
      that accompany the placement of axial fluorines on a cyclohexane and the unusual
      property of a facially polarized ring in organic chemistry. Derivatives have
      potential as new motifs for the design of functional organic molecules or for
      applications in supramolecular chemistry design. 

PMID- 25991527
TI  - Applying green chemistry to the photochemical route to artemisinin.
AB  - Artemisinin is an important antimalarial drug, but, at present, the environmental
      and economic costs of its semi-synthetic production are relatively high. Most of
      these costs lie in the final chemical steps, which follow a complex acid- and
      photo-catalysed route with oxygenation by both singlet and triplet oxygen. We
      demonstrate that applying the principles of green chemistry can lead to
      innovative strategies that avoid many of the problems in current photochemical
      processes. The first strategy combines the use of liquid CO2 as solvent and a
      dual-function solid acid/photocatalyst. The second strategy is an ambient
      temperature reaction in aqueous mixtures of organic solvents, where the only
      inputs are dihydroartemisinic acid, O2 and light, and the output is pure,
      crystalline artemisinin. Everything else-solvents, photocatalyst and aqueous acid
      can be recycled. Some aspects developed here through green chemistry are likely
      to have wider application in photochemistry and other reactions. 

PMID- 25991528
TI  - The critical role of phase-transfer catalysis in aprotic sodium oxygen batteries.
AB  - In the search for improved energy storage, rechargeable metal-oxygen batteries
      are very attractive owing to their reliance on molecular oxygen, which forms
      oxides on discharge that decompose reversibly on charge. Much focus has been
      directed at aprotic Li-O2 cells, but the aprotic Na-O2 system is of equal
      interest because of its better reversibility. We report here on the critical role
      and mechanism of phase-transfer catalysis in Na-O2 batteries. We find that it is
      solely responsible for the growth and dissolution of micrometre-sized cubic NaO2
      crystals and for the reversible cell capacity. In the absence of phase-transfer
      catalysis, quasi-amorphous NaO2 films are formed and cells exhibit negligible
      capacity. Electrochemical investigations provide a measure of the transportation
      of superoxide from the carbon electrode to the electrolyte phase by the phase
      transfer catalyst. This leads to a new understanding of the mechanism of Na-O2
      batteries that, significantly, extends to Li-O2 cells and explains their
      different behaviour. 

PMID- 25991529
TI  - Freeze-thaw cycles as drivers of complex ribozyme assembly.
AB  - The emergence of an RNA catalyst capable of self-replication is considered a key
      transition in the origin of life. However, how such replicase ribozymes emerged
      from the pools of short RNA oligomers arising from prebiotic chemistry and non
      enzymatic replication is unclear. Here we show that RNA polymerase ribozymes can
      assemble from simple catalytic networks of RNA oligomers no longer than 30
      nucleotides. The entropically disfavoured assembly reaction is driven by
      iterative freeze-thaw cycles, even in the absence of external activation
      chemistry. The steep temperature and concentration gradients of such cycles
      result in an RNA chaperone effect that enhances the otherwise only partially
      realized catalytic potential of the RNA oligomer pool by an order of magnitude.
      Our work outlines how cyclic physicochemical processes could have driven an
      expansion of RNA compositional and phenotypic complexity from simple oligomer
      pools. 

PMID- 25991530
TI  - Stabilization of elusive silicon oxides.
AB  - Molecular SiO2 and other simple silicon oxides have remained elusive despite the
      indispensable use of silicon dioxide materials in advanced electronic devices.
      Owing to the great reactivity of silicon-oxygen double bonds, as well as the low
      oxidation state of silicon atoms, the chemistry of simple silicon oxides is
      essentially unknown. We now report that the soluble disilicon compound, L:Si=Si:L
      (where L: = :C{N(2,6-(i)Pr2C6H3)CH}2), can be directly oxidized by N2O and O2 to
      give the carbene-stabilized Si2O3 and Si2O4 moieties, respectively. The nature of
      the silicon oxide units in these compounds is probed by spectroscopic methods,
      complementary computations and single-crystal X-ray diffraction. 

PMID- 25991531
TI  - A molecular shuttle that operates inside a metal-organic framework.
AB  - A 'molecular shuttle' is an interlocked molecular assembly in which a macrocyclic
      ring is able to move back and forth between two recognition sites. This large
      amplitude translational motion was first characterized in solution in 1991. Since
      that report, many mechanically interlocked molecules (MIMs) have been designed,
      synthesized and shown to mimic the complex functions of macroscopic switches and
      machines. Here, we show that this fundamental concept-the translational motion of
      a molecular shuttle-can be organized, initiated and made to operate inside a
      crystalline, solid-state material. A metal-organic framework (MOF) designated
      UWDM-4 was prepared that contains a rigid linker that is a molecular shuttle. It
      was demonstrated by variable-temperature (1)H-(13)C cross-polarization/magic
      angle spinning (CP/MAS) and (13)C 2D exchange correlation spectroscopy (EXSY)
      solid-state NMR at 21.1 T on a (13)C-enriched sample that the macrocyclic ring
      undergoes rapid shuttling along the rigid axle built between struts of the
      framework. 

PMID- 25991532
TI  - Adsorption-induced auto-amplification of enantiomeric excess on an achiral
      surface.
AB  - The homochirality of biomolecules is a signature of life on Earth and has
      significant implications in, for example, the production of pharmaceutical
      compounds. It has been suggested that biomolecular homochirality may have arisen
      from the amplification of a spontaneously formed small enantiomeric excess
      (e.e.). Many minerals exhibit naturally chiral surfaces and so adsorption has
      been proposed as one possible mechanism for such an amplification of e.e. Here we
      show that when gas-phase mixtures of D- and L-aspartic acid are exposed to an
      achiral Cu(111) surface, a small e.e. in the gas phase, e.e.g, leads to an
      amplification of the e.e. on the surface, e.e.s, under equilibrium conditions.
      Adsorption-induced amplification of e.e. does not require a chiral surface. The
      dependence of e.e.s on e.e.g has been modelled successfully using a Langmuir-like
      adsorption isotherm that incorporates the formation of homochiral adsorbate
      clusters on the surface. 

PMID- 25991533
TI  - An infinite chainmail of M6L6 metallacycles featuring multiple Borromean links.
AB  - Borromean rings or links are topologically complex assemblies of three entangled
      rings where no two rings are interlinked in a chain-like catenane, yet the three
      rings cannot be separated. We report here a metallacycle complex whose
      crystalline network forms the first example of a new class of entanglement. The
      complex is formed from the self-assembly of CuBr2 with the cyclotriveratrylene
      scaffold ligand (+/-)-tris(iso-nicotinoyl)cyclotriguaiacylene. Individual
      metallacycles are interwoven into a two-dimensional chainmail network where each
      metallacycle exhibits multiple Borromean-ring-like associations with its
      neighbours. This only occurs in the solid state, and also represents the first
      example of a crystalline infinite chainmail two-dimensional network. Crystals of
      the complex were twinned and have an unusual hollow tubular morphology that is
      likely to result from a localized dissolution-recrystallization process. 

PMID- 25991534
TI  - Homely holmium.

PMID- 25991535
TI  - Prevalence and pathology of vascular occlusive disease in the antiphospholipid
      syndromes.
AB  - Vascular occlusive disease occurs not infrequently in patients with
      antiphospholipid syndromes (APS) and, in some, may be associated with
      catastrophic complications. Recurrent, large- and small-vessel, arterial and/or
      venous thrombosis, and not vasculitis, is the only known and proven pathologic
      basis of virtually all clinical manifestations of APS in systemic, pulmonary,
      and/or cerebral circulations. Whether the vasculopathy of APS is thrombosis or
      vasculitis is of more than mere academic interest; the distinction is important
      not only for unravelling the pathogenesis of vascular injuries in APS but also
      for making the correct choice of drug treatment. A diagnosis of vasculitis would
      call for treatment with immunosuppressive and cytotoxic agents replete with
      undesirable and serious side effects. Furthermore, these powerful, but
      potentially dangerous, drugs are quite ineffectual in resolving or preventing the
      thrombosis associated with APS, which has been demonstrated clinically to respond
      to the lowly and inexpensive aspirin. 

PMID- 25991536
TI  - The spatial and temporal distribution of insulin-like growth factor-1 following
      experimental myocardial infarction in the rat.
AB  - Insulin-like growth factor-1 (IGF-1) is believed to be involved in the repair and
      adaptation that follow ischemic injury to the myocardium. The aim of this study
      was to elucidate the role of IGF-1 by defining the changes that occur in its
      distribution following regional myocardial infarction. The left anterior
      descending coronary artery was ligated in adult male Wistar rats, and hearts were
      examined microscopically from 6 hours to 20 days later. IGF-1 was identified
      histochemically using the avitin-biotin-peroxidase method with a polyclonal
      antibody to IGF-1 and was quantified by optical density measurements of standard
      fields in sections of hearts prepared in a single batch. Immunoreactivity was
      located in the cytoplasm of viable myocytes, vascular smooth-muscle cells, mast
      cells, leukocytes, endothelial cells, and fibroblasts. The zone of viable
      myocardium immediately adjacent to infarcts reacted significantly more intensely
      for IGF-1 than all other regions at all stages, with a maximum optical density
      (617% higher than sham-operated control myocardium, p < .001) 24 hours after
      coronary artery ligation. Immunoreactivity in myocardium tissue distant from the
      infarcts also increased during the first day (382% at 24 hours), but this
      increase was not statistically significant thereafter. These temporal and spatial
      changes in the distribution and amount of IGF-1 indicate that this finding is
      predominantly associated with a localized response to injury by the viable
      myocytes adjacent to infarcts. 

PMID- 25991537
TI  - Histopathology of thalassemic heart disease: an endomyocardial biopsy study.
AB  - Right ventricle endomyocardial biopsies were obtained from 13 thalassemic
      patients. Clinical profiles were investigated, and serum ferritin tests were
      assessed using diagnostic kits. Histochemical iron detection (Perls method) and
      immunohistochemical stain for ferritin were performed in the endomyocardial
      samples. Histologic iron overload was observed in eight patients, and variable
      iron deposits were recognized by a semiquantitative method. There was a
      statistically evident correlation between serum ferritin and myocardial iron
      storage. Marked iron deposition was associated with higher immunohistologic
      ferritin concentration. Iron-negative tissue samples showed bland
      immunohistochemical positivity. Myocardial interstitial fibrosis was observed in
      12 cases; diffuse perimyocytic or perivascular fibrosis and endocardium
      thickening were the main histologic patterns identified. One biopsy was
      characterized by marked fibrolipomatous infiltration. Myocyte hypertrophy,
      myocytolysis, and severe capillary congestion also were observed. 

PMID- 25991538
TI  - Adventitial layer enlargement correlates with the percentage of medial thickness
      in peripheral pulmonary arteries from patients with congenital heart defects.
AB  - Arterial walls undergo modifications during the course of pulmonary hypertension,
      particularly in the medial and intimal layers, leading to progressive occlusion
      of the lumen. Adventitial layer enlargement has been described as being present
      in the experimental hypoxic model and in the persistent pulmonary hypertension of
      the newborn. It was suggested that this enlargement may be related to stimulating
      factors derived from the medial smooth muscle cells. This study was designed to
      verify if different degrees of medial hypertrophy are correlated to the volume
      density of the adventitial layer in pulmonary hypertension secondary to
      congenital heart defects. Reviewing 21 lung biopsies from patients with
      congenital heart defects, we concluded that there is a statistically significant
      positive linear correlation between the mean percentage of medial arterial
      thickness and the volume density of the adventitial layer in the biopsies showing
      isolated medial hypertrophy. On the other hand, in biopsies showing frequent
      intimal proliferative lesions and irregular medial layer hypertrophy the
      correlation coefficient was lower. These findings suggest that the adventitial
      layer participates in the arterial remodeling process in secondary pulmonary
      hypertension, and that its enlargement depends on the qualitative degree of
      pulmonary vaso-occlusive disease. 

PMID- 25991539
TI  - Current Progress in Anticalcif ication for Bioprosthetic and Polymeric Heart
      Valves.
AB  - The use of bioprosthetic valves fabricated from fixed heterograft tissue (porcine
      aortic valves or bovine pericardium) in heart valve replacement surgery is
      limited because of calcification-related failures. The mechanism of calcification
      of bioprosthetic valves is quite complex and has a variety of determinants,
      including host factors, tissue fixation conditions, and mechanical effects.
      Currently, there is no effective therapy to prevent calcification in clinical
      settings. This article reviews a variety of anticalcification strategies that are
      under investigation either in advanced animal models or in clinical trials.
      Bisphosphonates, such as ethan hydroxybisphosphonate (EHBP), inhibit calcium
      phosphate crystal formation. However, because of their systemic toxicity, they
      are used as either tissue treatments or polymeric site-specific delivery systems.
      Detergent treatment, such as sodium dodecyl sulfate (SDS), extracts almost all
      phospholipids from bioprosthetic heart valve cuspal tissue. Procedures, such as
      amino oleic acid pretreatment, inhibit calcium uptake. Polyurethane trileaflet
      valves, investigated as alternatives to bioprosthetic or mechanical valve
      prostheses, undergo intrinsic and thrombus-related calcification and degradation.
      Calcification- and thrombus-resistant polyurethanes synthesized in our laboratory
      by covalent linking of EHBP or heparin (either in bulk or on surface) by unique
      polyepoxidation chemistry are attractive candidates for further research. Tissue
      engineered heart valves may have an important place in the future. 

PMID- 25991540
TI  - Aschoff bodies in an operatively excised mitral valve.
AB  - Aschoff bodies are granulomatous lesions believed to be pathognomonic of
      rheumatic fever. Most histologic descriptions have been limited to locations
      adjacent to or within the myocardium. Aschoff bodies within valves are uncommon
      findings. We report a case showing the typical granulomas in an excised mitral
      valve. We suggest that Aschoff bodies can, and do, occur in valve tissue during
      acute rheumatic carditis and that structural differences between valves and
      typical intramyocardial locations, variations in frequency and strength of
      individual infections, individual host responses, and time intervals between
      infection and histologic examination often obscure their findings in valves. 

PMID- 25991541
TI  - Transient loss of vision as the presenting symptom of papillary fibroelastoma of
      aortic valve.
AB  - Cardiac papillary fibroelastomas are benign endocardial papillomas. They may
      arise from atrial or ventricular endocardium but most commonly are located in
      cardiac valves. Their papillary structure, with loose, friable projections,
      results in a high tendency for embolism. Tumor fragments often embolize to the
      coronary, systemic, or cerebral arterial systems. Thus, acute myocardial
      infarction, cerebrovascular accident, or peripheral arterial occlusion have
      resulted from these tumors. Retinal artery embolism is a rare complication of
      papillary fibroelastoma, and only five such patients have been reported in the
      English-language literature. We describe a 64-year-old woman who presented with
      transient painless loss of vision and was found to have a large papillary
      fibroelastoma on the right coronary cusp of the aortic valve by transesophageal
      echocardiography. The tumor was successfully removed at surgery. 

PMID- 25991543
TI  - Effect of beta-Mannanase and beta-Mannosidase Supplementation on the Total
      Hydrolysis of Softwood Polysaccharides by the Talaromyces cellulolyticus
      Cellulase System.
AB  - Softwoods are promising lignocellulosic feedstock that provide numerous
      fermentable sugars via the hydrolysis of the components of cellulose and mannan
      type hemicellulose such as galactoglucomannan (GGM). However, fungal cellulase
      systems are insufficient for the hydrolysis of softwood GGM due to the relatively
      low levels of mannan-degrading activities. To compensate for the deficient
      activities in the cellulase system, mannan-degrading enzymes were added to a
      cellulase preparation from Talaromyces cellulolyticus and the hydrolysis of a
      ball-milling-treated Douglas fir (BM-DF) was evaluated. The addition of a
      commercial enzyme derived from Aspergillus niger with high beta-mannanase and
      beta-mannosidase activities resulted in approximately 80 % mannose yield from BM
      DF for a small protein loading amount (i.e., 1.4 mg/g substrate). Supplementation
      of beta-mannanase and beta-mannosidase purified from the commercial enzyme
      revealed that both enzymes were essential to improve the hydrolysis of BM-DF GGM
      by T. cellulolyticus cellulase. T. cellulolyticus produced inducible mannan
      degrading enzymes using glucomannan as a carbon source. Supplementation of this
      enzyme preparation increased mannose yield from BM-DF to approximately 70 %.
      These results suggest that the enhancement of T. cellulolyticus beta-mannosidase
      and beta-mannanase productivity will be effective for the construction of
      cellulase system suitable for BM-DF hydrolysis.

PMID- 25991542
TI  - A meta-analysis of anterior cruciate ligament reconstruction with autograft
      compared with nonirradiated allograft.
AB  - BACKGROUND: To compare autograft with non-irradiated allograft for reconstruction
      of anterior cruciate ligament. METHODS: MEDLINE, EMBASE, and Cochrane Library
      databases, as well as unpublished and ongoing studies were searched through up to
      20 July 2013 to identify studies meeting the pre-stated inclusion criteria.
      RESULTS: A total of 12 studies (n=1167, including 597 patients in the autograft
      group and 570 patients in the allograft group) were included. The methodological
      scores for randomized controlled trials ranged from two to four (total score:
      seven), and for non-randomized prospective studies and cohort studies ranged from
      four to seven (total score: 12). Except for the Lysholm score (WMD, -1.46;
      P<0.05) showing a statistically significant difference but a small and clinically
      irrelevant difference, there was no significant difference between autograft and
      non-irradiated allograft with respect to the overall IKDC (International Knee
      Documentation Committee) level, subjective IKDC score, Tegner score,
      complication, ROM (range of motion), Pivot-shift test, Anterior drawer test,
      Lachman test, Daniel's one-leg hop test, Harner's vertical jump test, and
      Instrumented knee laxity test. The results were consistent across a series of
      sensitivity analyses and subgroup analyses. CONCLUSIONS: Patients with autograft
      exhibited little clinical advantage over non-irradiated allograft with respect to
      knee stability, function and side effects. The robustness of the findings might
      need to be further validated due to the relatively small number of randomized
      controlled trials. LEVEL OF EVIDENCE: Level II, meta-analysis of prospective
      studies.

PMID- 25991544
TI  - Detection of Orthobunyavirus in mosquitoes collected in Argentina.
AB  - Bunyamwera virus (BUNV) (Bunyaviridae, genus Orthobunyavirus, serogroup
      Bunyamwera) is considered an emerging pathogen for humans and animals in American
      countries. The CbaAr-426 strain of BUNV was recovered from mosquitoes
      Ochlerotatus albifasciatus (Diptera: Culicidae) collected in Cordoba province
      (Argentina), where serological studies detected high seroprevalences in humans
      and animals. Molecular detection of Orthobunyavirus was performed in mosquitoes
      collected in Cordoba province. Seventeen mosquito pools of Oc. albifasciatus,
      Ochlerotatus scapularis and Culex quinquefasciatus (Diptera: Culicidae) showed
      positive results; four of these positive pools, all of Oc. scapularis, were
      sequenced. All amplicons grouped with BUNV in the Bunyamwera serogroup. The
      findings highlight the circulation of BUNV in Cordoba province and represent the
      first report of BUNV-infected Oc. scapularis mosquitoes in Argentina. 

PMID- 25991545
TI  - Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast
      Cancer.
AB  - The formation of a new blood vessel is stimulated by angiogenic factors.
      Curcumin, which is the active ingredient of the spice plant Curcuma longa L and
      is used as food and traditional medicine, has shown anticancer effects against
      different types of cancers. We evaluated the effects of curcumin on
      angiogenesis/pro-angiogenic factors in a mouse model of human breast cancer. Cell
      viability was measured by the MTT assay after curcumin treatment in triple
      negative breast cancer cells (MDA-MB-231). For the in vivo study, human breast
      cancer was induced in athymic mice and treated with 300 mg/kg/day of curcumin
      administered intraperitoneally. Tumor size was measured weekly, and the animals
      underwent single photon emission computed tomography (SPECT) scanning with Tc-99m
      tagged VEGF-c to detect the in vivo expression of VEGFR2/3. In addition, the
      expression of proangiogenic/ growth factors in the tumor extracts was evaluated
      by a membrane antibody array. Histological analysis was performed to confirm the
      effect of curcumin on neovascularization. The MTT assay showed that curcumin
      significantly reduced the cell viability of MDA-MB-231 cells. In breast cancer
      xenografts, curcumin treatment led to a decrease in tumor volume and cell
      proliferation (Ki-67) compared with the vehicle treated group. Tc-99m-HYNIC-VEGF
      c-SPECT imaging showed decreased uptake to the tumor, which may indicate a lower
      expression of VEGFR2/3 in curcumin treated tumors; however, a statistically
      significant difference was not achieved (p>0.05). Additionally, curcumin
      treatment showed a significantly low level of expression of pro-angiogenic
      factors (p<0.05) and a decrease in micro-vessel density (vWF) in animals compared
      with that of vehicle treated tumors. In conclusion, curcumin treatment showed
      effectiveness in reducing tumor growth and cell proliferation, as well as in the
      inhibition of angiogenesis. 

PMID- 25991546
TI  - Promotion of Metastasis-associated Gene Expression in Survived PANC-1 Cells
      Following Trichostatin A Treatment.
AB  - OBJECTIVES: Histone deacetylase inhibitors represent a promising class of
      potential anticancer agents for the treatment of human malignancies. In this
      study, the effects of trichostatin A (TSA) on apoptosis, metastasis-associated
      gene expression, and activation of the Notch pathway in human pancreatic cancer
      cell lines were investigated. METHODS: After treatment with TSA, cell viability
      and apoptosis were evaluated using the MTT [3-(4,5-dimethylthia-zol-2-yl)-2,5
      diphenyltetrazolium bromide] assay, Hoechst 33258 staining, and flow cytometry.
      Moreover, RT-PCR and western blot analyses were performed to measure the
      expression levels of apoptosis-associated genes (Bcl-2, Bax, and caspase-3),
      metastasis-associated genes (E-cadherin, vimentin, and matrix
      metalloproteinases), and Notch pathway activation (Notch intracellular domain,
      NICD). The levels of matrix metalloproteinase 2 and NICD were also semi
      quantified by immunoassay. RESULTS: Following treatment with TSA for 24 h, PANC
      1, SW1990, and MIATACA-2 cells exhibited cell death. The MTT assay revealed that
      TSA significantly decreased cell viability in a dose-dependent manner in PANC-1
      cells. The Hoechst 33258 staining and flow cytometry results evidenced a
      significant increase in PANC-1 cell apoptosis following TSA treatment. The
      expression levels of Bax and caspase-3 were increased significantly, whereas Bcl
      2 was down-regulated after TSA treatment. In the PANC-1 cells that survived after
      TSA treatment, the expression levels of vimentin, E-cadherin, and MMP genes were
      altered by the promotion of potential metastasis and increased expression of
      NICD. CONCLUSIONS: TSA can induce apoptosis of pancreatic cancer cells. In
      addition, the up-regulation of metastasis-related genes and the activation of the
      Notch pathway in the survived PANC-1 cells may be associated with a too-low level
      of TSA or resistance to TSA.

PMID- 25991547
TI  - Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation.
AB  - Pyruvate dehydrogenase kinases (PDKs) modulate energy homeostasis in multiple
      tissues and cell types, under various nutrient conditions, through
      phosphorylation of the alpha subunit (PDHE1alpha, also known as PDHA1) of the
      pyruvate dehydrogenase (PDH) complex. However, the roles of PDKs in meiotic
      maturation are currently unknown. Here, by undertaking knockdown and
      overexpression analysis of PDK paralogs (PDK1-PDK4) in mouse oocytes, we
      established the site-specificity of PDKs towards the phosphorylation of three
      serine residues (Ser232, Ser293 and Ser300) on PDHE1alpha. We found that PDK3
      mediated phosphorylation of Ser293-PDHE1alpha results in disruption of meiotic
      spindle morphology and chromosome alignment and decreased total ATP levels,
      probably through inhibition of PDH activity. Unexpectedly, we discovered that
      PDK1 and PDK2 promote meiotic maturation, as their knockdown disturbs the
      assembly of the meiotic apparatus, without significantly altering ATP content.
      Moreover, phosphorylation of Ser232-PDHE1alpha was demonstrated to mediate PDK1
      and PDK2 action in meiotic maturation, possibly through a mechanism that is
      distinct from PDH inactivation. These findings reveal that there are divergent
      roles of PDKs during oocyte maturation and indicate a new mechanism controlling
      meiotic structure. 

PMID- 25991548
TI  - A Brn2-Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic
      stem cells.
AB  - Mouse embryonic stem cells (ESCs) treated with all-trans retinoic acid
      differentiate into a homogenous population of glutamatergic neurons. Although
      differentiation is initiated through activation of target genes by the retinoic
      acid receptors, the downstream transcription factors specifying neuronal fate are
      less well characterised. Here, we show that the transcription factor Brn2 (also
      known as Pou3f2) is essential for the neuronal differentiation programme. By
      integrating results from RNA-seq following Brn2 silencing with results from Brn2
      ChIP-seq, we identify a set of Brn2 target genes required for the neurogenic
      programme. Further integration of Brn2 ChIP-seq data from retinoic-acid-treated
      ESCs and P19 cells with data from ESCs differentiated into neuronal precursors by
      Fgf2 treatment and that from fibroblasts trans-differentiated into neurons by
      ectopic Brn2 expression showed that Brn2 occupied a distinct but overlapping set
      of genomic loci in these differing conditions. However, a set of common binding
      sites and target genes defined the core of the Brn2-regulated neuronal programme,
      among which was that encoding the transcription factor Zic1. Small hairpin RNA
      (shRNA)-mediated silencing of Zic1 prevented ESCs from differentiating into
      neuronal precursors, thus defining a hierarchical Brn2-Zic1 axis that is
      essential to specify neural fate in retinoic-acid-treated ESCs. 

PMID- 25991549
TI  - Preventing sex offences: the Dunkelfeld project.

PMID- 25991550
TI  - Evaluation of the protective effect of Pterocarpus marsupium on acetic acid
      induced ulcerative colitis in rats.
AB  - The aim of the study was to evaluate the effect of Pterocarpus marsupium (PM) on
      acetic acid (AA)-induced ulcerative colitis (UC) in rats. The rats were divided
      into five groups, each having six rats. PM extract 100 mg and 200 mg/kg was given
      orally to groups four and five, respectively, and standard drug sulfasalazine
      (100 mg/kg, p.o) to group three. Group two served as UC control animals, and
      group one control animals received vehicle for 7 days. UC was induced by
      administering AA (3 % v/v of 2 ml) to all the animals except group one. After 72
      h, the animals were killed and the colon was dissected out for microscopic,
      clinical evaluation, histopathological study and biochemical estimation. PM (100
      and 200 mg/kg)-treated group had significantly reduced colon inflammation and
      mucosal damage. The treatment also normalized the altered antioxidant enzyme
      levels (LPO, SOD and GSH). Histopathological studies support the effect. The
      protective effect of PM may be due to antiinflammatory and antioxidant
      properties. 

PMID- 25991551
TI  - Interference of lateralized distractors on arithmetic problem solving: a
      functional role for attention shifts in mental calculation.
AB  - Solving arithmetic problems has been shown to induce shifts of spatial attention
      in simple probe-detection tasks, subtractions orienting attention to the left
      side and additions to the right side of space. Whether these attentional shifts
      constitute epiphenomena or are critically linked to the calculation process is
      still unknown. In the present study, we investigate participants' performance on
      addition and subtraction solving while they have to detect central or lateralized
      targets. The results show that lateralized distractors presented in the hemifield
      congruent to the operation to be solved interfere with arithmetical solving:
      participants are slower to solve subtractions or additions when distractors are
      located on the left or on the right, respectively. These results converge with
      previous data to show that attentional shifts underlie not only number processing
      but also mental arithmetic. They extend them as they reveal the reverse effect of
      the one previously reported by showing that inducing attention shifts interferes
      with the solving of arithmetic problems. They also demonstrate that spatial
      attentional shifts are part of the calculation procedure of solving mentally
      arithmetic problems. Their functional role is to access, from the first operand,
      the representation of the result in a direction congruent to the operation. 

PMID- 25991552
TI  - Transition from two to one integument in Prunus species: expression pattern of
      INNER NO OUTER (INO), ABERRANT TESTA SHAPE (ATS) and ETTIN (ETT).
AB  - While gymnosperm ovules have one integument, in most angiosperms two integuments
      surround the ovules. Unitegmic ovules have arisen independently several times
      during the evolution of angiosperms, but the ultimate genetic cause of the
      presence of a single integument remains elusive. We compared species of the genus
      Prunus that have different numbers of integuments: bitegmic species, such as
      Prunus armeniaca (apricot) and Prunus persica (peach), and unitegmic species,
      such as Prunus incisa, analyzing the expression pattern of genes that are
      involved in integument development in Arabidopsis thaliana: INNER NO OUTER (INO),
      ABERRANT TESTA SHAPE (ATS) and ETTIN (ETT). Bitegmic and unitegmic species showed
      similar INO expression patterns, indicative of the conservation of an outer
      integument. However, expression of ETT, which occurs in the boundary of the outer
      and inner integuments, was altered in unitegmic ovules, which showed lack of ETT
      expression. These results strongly suggest that the presence of a single
      integument could be attributable to the amalgamation of two integuments and
      support the role of ETT in the fusion of the outer and inner integuments in
      unitegmic ovules, a situation that could be widespread in other unitegmic species
      of angiosperms. 

PMID- 25991554
TI  - Contemporary spinal cord protection during thoracic and thoracoabdominal aortic
      surgery and endovascular aortic repair: a position paper of the vascular domain
      of the European Association for Cardio-Thoracic Surgery?.
AB  - Ischaemic spinal cord injury (SCI) remains the Achilles heel of open and
      endovascular descending thoracic and thoracoabdominal repair. Neurological
      outcomes have improved coincidentially with the introduction of neuroprotective
      measures. However, SCI (paraplegia and paraparesis) remains the most devastating
      complication. The aim of this position paper is to provide physicians with broad
      information regarding spinal cord blood supply, to share strategies for
      shortening intraprocedural spinal cord ischaemia and to increase spinal cord
      tolerance to transitory ischaemia through detection of ischaemia and augmentation
      of spinal cord blood perfusion. This study is meant to support physicians caring
      for patients in need of any kind of thoracic or thoracoabdominal aortic repair in
      decision-making algorithms in order to understand, prevent or reverse ischaemic
      SCI. Information has been extracted from focused publications available in the
      PubMed database, which are cohort studies, experimental research reports, case
      reports, reviews, short series and meta-analyses. Individual chapters of this
      position paper were assigned and after delivery harmonized by Christian D. Etz,
      Ernst Weigang and Martin Czerny. Consequently, further writing assignments were
      distributed within the group and delivered in August 2014. The final version was
      submitted to the EJCTS for review in September 2014. 

PMID- 25991553
TI  - Expression of the miR-302/367 cluster in glioblastoma cells suppresses
      tumorigenic gene expression patterns and abolishes transformation related
      phenotypes.
AB  - Cellular transformation is initiated by the activation of oncogenes and a closely
      associated developmental reprogramming of the epigenetic landscape. Transcription
      factors, regulators of chromatin states and microRNAs influence cell fates in
      development and stabilize the phenotypes of normal, differentiated cells and of
      cancer cells. The miR-302/367 cluster, predominantly expressed in human embryonic
      stem cells (hESs), can promote the cellular reprogramming of human and mouse
      cells and contribute to the generation of iPSC. We have used the epigenetic
      reprogramming potential of the miR-302/367 cluster to "de-program" tumor cells,
      that is, hift their gene expression pattern towards an alternative program
      associated with more benign cellular phenotypes. Induction of the miR-302/367
      cluster in extensively mutated U87MG glioblastoma cells drastically suppressed
      the expression of transformation related proteins, for example, the reprogramming
      factors OCT3/4, SOX2, KLF4 and c-MYC, and the transcription factors POU3F2, SALL2
      and OLIG2, required for the maintenance of glioblastoma stem-like tumor
      propagating cells. It also diminished PI3K/AKT and STAT3 signaling, impeded
      colony formation in soft agar and cell migration and suppressed pro-inflammatory
      cytokine secretion. At the same time, the miR-302/367 cluster restored the
      expression of neuronal markers of differentiation. Most notably, miR-302/367
      cluster expressing cells lose their ability to form tumors and to establish liver
      metastasis in nude mice. The induction of the miR-302/367 cluster in U87MG
      glioblastoma cells suppresses the expression of multiple transformation related
      genes, abolishes the tumor and metastasis formation potential of these cells and
      can potentially become a new approach for cancer therapy. 

PMID- 25991555
TI  - Amino acid conversions by coagulase-negative staphylococci in a rich medium:
      Assessment of inter- and intraspecies heterogeneity.
AB  - The ability of coagulase-negative staphylococci (CNS) to convert amino acids into
      volatile compounds and biogenic amines was investigated after 24h and 48 h of
      incubation in a rich medium (brain heart infusion). Volatile compounds were
      measured with static-headspace gas chromatography and mass spectrometry (SH-GC
      MS); biogenic amine measurements were carried out with a newly developed method
      based on ultra-performance liquid chromatography coupled to tandem mass
      spectrometry (UPLC-MS/MS). In total, 56 CNS strains from five different species
      were used, namely Staphylococcus carnosus, Staphylococcus epidermidis,
      Staphylococcus equorum, Staphylococcus saprophyticus, and Staphylococcus xylosus.
      With respect to the production of volatile compounds, the leucine-derived 3
      methyl butanol was produced over time by most CNS strains, up to 52 MUM for S.
      xylosus W1-1 after 48 h of incubation. The average production by strains of S.
      xylosus was significantly higher than for strains of S. carnosus, whereas strains
      of S. epidermidis turned out to be poor producers. Yet, differences between
      species were blurred to a large degree because of the high strain variability. A
      few strains also produced 3-methyl butanal on top of the amount that was already
      present in the medium background, although most CNS led to a decrease of this
      compound. Concerning biogenic amines, the average total concentrations per
      species remained below 100 MUM after 48 h of incubation. The most abundant
      variant was 2-phenylethylamine (PEA), especially within S. carnosus (average of
      65 MUM after 48 h of incubation). Yet, some individual strains were able to
      produce higher concentrations, as found for the PEA production of 295 MUM by S.
      epidermidis ATCC 12228 after 48 h of incubation. The insights obtained during
      this study indicate heterogeneity and are of importance in view of both starter
      culture development and the evaluation of a spontaneously established CNS
      microbiota in artisan-type meat fermentations.

PMID- 25991556
TI  - A worm of one's own: how helminths modulate host adipose tissue function and
      metabolism.
AB  - Parasitic helminths have coexisted with human beings throughout time. Success in
      eradicating helminths has limited helminth-induced morbidity and mortality but is
      also correlated with increasing rates of 'western' diseases, including metabolic
      syndrome and type 2 diabetes. Recent studies in mice describe how type 2 immune
      cells, traditionally associated with helminth infection, maintain adipose tissue
      homeostasis and promote adipose tissue beiging, protecting against obesity and
      metabolic dysfunction. Here, we review these studies and discuss how helminths
      and helminth-derived molecules may modulate these physiologic pathways to improve
      metabolic functions in specific tissues, such as adipose and liver, as well as at
      the whole-organism level. 

PMID- 25991558
TI  - Child psychiatric epidemiology: stars and hypes.

PMID- 25991559
TI  - Oxidative stress-related genes in type 2 diabetes: association analysis and their
      clinical impact.
AB  - Worldwide prevalence of diabetes mellitus motivates a number of association
      studies to be conducted throughout the world. Eleven polymorphisms from nine
      candidate genes in oxidative stress pathway have been analyzed in eastern Indian
      type 2 diabetic patients (n = 145) and healthy controls (n = 100). Different
      biochemical parameters were also analyzed for their association with the disease.
      Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI
      2.265-8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116-5.512, P <
      0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071-4.969, P < 0.001), RAGE
      rs1800624 -374 T>A (OR 3.58, 95% CI 2.218-5.766, P < 0.001), and NOS3 -786 T>C
      (OR 3.75, 95% CI 2.225-6.666, P < 0.001). Haplotype containing two risk alleles
      of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI
      1.554-44.804, P < 0.002). Our results suggest that carriers of major and
      efficient alleles of oxidative stress genes are more likely to survive the
      comorbid complications and single copy of risk allele is sufficient for
      developing the disease.

PMID- 25991557
TI  - Arterial stiffness and increased cardiovascular risk in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a global public health problem. Cardiovascular
      disease (CVD) is a common comorbidity and a major cause of mortality in CKD
      population. While CVD-related mortality is relatively uncommon in young
      population, it accounts for most deaths in young CKD adults. There are numerous
      risk factors for CVD in CKD patients including conventional (hypertension,
      diabetes, dyslipidemia) and nonconventional (oxidative stress, inflammation,
      anemia, mineral metabolism disorder) factors. Recent studies have placed great
      emphasis on the association of arterial stiffness (AS) and CVD. AS is
      traditionally known as an aging marker of the artery; however, increased AS is
      observed in young and even in pediatric CKD patients; it is also shown that AS
      progresses in consistent with kidney function decline. Unparallel AS in young CKD
      population and excessive risk of CVD in young CKD adults show an indication that
      AS probably offers one of the underlying mechanisms for linking CKD and CVD. AS
      in CKD patients has multifactorial causes. Comorbidities such as hypertension,
      diabetes, dyslipidemia, and mineral metabolism disorder which are risk factors
      for CVD also show great contribution to AS in CKD patients. Increased systolic
      blood pressure and decreased diastolic blood pressure resulting from AS cause
      elevated ventricular afterload, lead to impaired coronary perfusion, myocardial
      ischemia, and ventricular hypertrophy, and consequently develop into CVD event.
      In this review, we summarized the role of AS in CKD and CVD, aiming to explore
      the linkage of AS between CKD and CVD. 

PMID- 25991560
TI  - Polymorphisms of the resistin gene and their association with obesity and
      resistin levels in Malaysian Malays.
AB  - Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to
      obesity and resistin levels in various populations. However, results have been
      inconsistent. This study aimed to investigate association between polymorphisms
      in the resistin gene with obesity in a homogenous Malaysian Malay population.
      This study is also aimed to determine association between resistin levels with
      certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were
      included in this study and genotyping was carried out using Sequenom MassARRAY.
      There was no significant difference found in both allelic and genotype
      frequencies of each of the RETN SNPs between the obese and non-obese groups after
      Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly
      associated with log-resistin levels. The GG genotype carriers are found to have
      higher levels of log-resistin compared to A allele carriers. The RETN haplotypes
      (CAG, CGA and GA) were significantly associated with resistin levels. However,
      the haplotypes of the RETN gene were not associated with obesity. Resistin levels
      were not correlated to metabolic parameters such as body weight, waist
      circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes
      are of apparent functional importance in the regulation of resistin levels but
      are not correlated with obesity and related markers. 

PMID- 25991561
TI  - Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical
      Research.
AB  - WNIN (Wistar/NIN) is an inbred rat strain maintained at National Institute of
      Nutrition (NIN) for more than 90 years, and WNIN/Ob is an obese mutant originated
      from it. To determine their genetic relatedness with major rat strains in
      biomedical research, they were genotyped at various marker loci. The recently
      identified markers for albino and hooded mutations which clustered all the known
      albino rats into a single lineage also included WNIN and WNIN/Ob rats. Genotyping
      using microsatellite DNA markers and phylogenetic analysis with 49 different rat
      strains suggested that WNIN shares a common ancestor with many Wistar originated
      strains. Fst estimates and Fischer's exact test suggest that WNIN rats differed
      significantly from all other strains tested. WNIN/Ob though shows hyper
      leptinemia, like Zucker fatty rat, did not share the Zucker fatty rat mutation.
      The above analyses suggest WNIN as a highly differentiated rat strain and WNIN/Ob
      a novel obese mutant evolved from it. 

PMID- 25991562
TI  - upQMPSF, a Method for the Detection of BRCA1 Exon Copy Number Variants.
AB  - Large insertions/deletions mutations are frequently found in genes associated
      with certain diseases such as hereditary cancers. These mutations are mostly
      overlooked by current classical screening techniques due to their certain
      limitations. This justifies the need to improve the existing techniques or design
      novel ones. A modified version of quantitative multiplex PCR short fluorescent
      fragment (QMPSF), termed universally primed QMPSF (upQMPSF), was developed. The
      modifications enhance multiplexing capacity, reduce cost, and improve the
      mutation detection spectrum. upQMPSF was used to screen germline mutations in 88
      familial ovarian cancer patients negative for point mutations. upQMPSF
      successfully detected a 2.8 kb copy number gain spanning exon 15 of BRCA1 gene
      mediated by Alu-Alu homologous-based recombination. upQMPSF is a cost-efficient,
      versatile method, and demonstrated efficiency in detecting structural variations
      as a potential method for genetic testing in clinical and research laboratories.

PMID- 25991563
TI  - Adjustments for weighing clothed babies at high altitude or in cold climates.
AB  - Public health nutritionists rely on anthropometry for nutritional assessment,
      program planning, and evaluation. Children are usually heavily clothed at high
      altitudes and in cold climates. Failing to adjust for clothing weight could
      underestimate malnutrition prevalence. The objective of this paper is to validate
      an adjustment process for estimating clothing weight and quantify potential
      misclassification error. In March and September 2009, 293 and 272 children under
      2 years of age, respectively, were measured for weight and length in 14 highlands
      communities in Ecuador. Weight-for-age z-scores (WAZ) and weight-for-height z
      scores (WHZ) were compared using clothing-unadjusted weights and two types of
      clothing-adjusted weights: individual clothing-weights and population-mean
      clothing-weights. Modelling showed up to 24% of children's nutritional status and
      degree of malnutrition were misclassified for WAZ, and 13% for WHZ, when clothing
      was not taken into account in this cold climate. Compared with the more time
      intensive individual clothing-weight adjustment, the population-mean clothing
      weight adjustments had high specificity and sensitivity for WAZ. In cold
      climates, adjusting for population mean clothing weight provides a better
      estimate of the prevalence of malnutrition to inform appropriate program
      decisions for addressing underweight. An individual clothing weight adjustment
      may also be essential to classify a specific child's nutritional status when
      acute malnutrition is a concern. 

PMID- 25991564
TI  - CRISPR-Cas9-mediated genome editing and guide RNA design.
AB  - CRISPR and CRISPR-associated (Cas) proteins, which in nature comprise the RNA
      based adaptive immune system in bacteria and archaea, have emerged as
      particularly powerful genome editing tools owing to their unrivaled ease of use
      and ability to modify genomes across mammalian model systems. As such, the CRISPR
      Cas9 system holds promise as a "system of choice" for functional mammalian
      genetic studies across biological disciplines. Here we briefly review this fast
      moving field, introduce the CRISPR-Cas9 system and its application to genome
      editing, with a focus on the basic considerations in designing the targeting
      guide RNA sequence. 

PMID- 25991566
TI  - Synthesis and photoluminescence characteristics of (Y,Gd)BO3:RE (RE = Eu(3+),
      Ce(3+), Dy(3+) and Tb(3+)) phosphors for blue chip and near-UV white LEDs.
AB  - A series of Eu(3+)-, Ce(3+)-, Dy(3+)- and Tb(3+)-doped (Y,Gd)BO3 phosphors was
      synthesized by a solid-state diffusion method. X-Ray diffraction confirmed their
      hexagonal structure and the scanning electron microscopy results showed
      crystalline particles. The excitation spectra revealed that (Y,Gd)BO3 phosphors
      doped with Eu(3+), Ce(3+), Dy(3+) and Tb(3+) are effectively excited with near UV
      light of 395 nm/blue light, 364, 351 and 314 nm, respectively. Photoluminescence
      spectra of Eu(3+)-, Ce(3+)- and Tb(3+)/Dy(3+)-doped phosphor showed intense
      emission of reddish orange, blue and white light, respectively. The phosphor
      Y0.60Gd0.38BO3:Ce0.02 showed CIE 1931 color coordinates of (0.158, 0.031) and
      better color purity compared with commercially available blue BAM:Eu(2+)
      phosphor. The phosphor (Y,Gd)BO3 doped with Eu(3+), Dy(3+) and Tb(3+) showed CIE
      1931 color coordinates of (0.667, 0.332), (0.251, 0.299) and (0.333, 0.391)
      respectively. Significant photoluminescence characteristics of the prepared
      phosphors indicate that they might serve as potential candidates for blue chip
      and near-UV white light-emitting diode applications.

PMID- 25991565
TI  - The preferences and perspectives of family caregivers towards place of care for
      their relatives at the end-of-life. A systematic review and thematic synthesis of
      the qualitative evidence.
AB  - BACKGROUND: Home is often reported as the preferred place of care for patients at
      the end-of-life. The support of family caregivers is crucial if this is to be
      realised. However, little is known about their preferences; a greater
      understanding would identify how best to support families at the end-of-life,
      ensuring more patients are cared for in their preferred location. OBJECTIVES: To
      systematically search and synthesise the qualitative literature exploring the
      preferences and perspectives of family caregivers towards place of care for their
      relatives at the end-of-life. METHODS: Ten databases (MEDLINE, PsycINFO, EMBASE,
      AMED, ASSIA, CINAHL, Social Care Online, Cochrane Database, Scopus, Web of
      Science) and reference lists of key journals were searched up to January 2014.
      Included studies were appraised for quality and data thematically synthesised.
      RESULTS: Eighteen studies were included; all were of moderate or high quality.
      Two main themes were identified: (1) Preferences and perspectives: most family
      caregivers preferred home care, although a range of perspectives were reported.
      Both positive and negative perspectives of home, hospices and hospitals emerged.
      At times, family caregivers reported feeling obligated to provide home care. (2)
      Impact of facilitating home care; both positive and negative effects on family
      caregivers were reported. CONCLUSIONS: Many family caregivers reported home as
      the preferred place of care; other places of care were infrequently considered.
      Healthcare professionals and service providers should be aware of these
      preferences and provide support where needed to enable family caregivers to
      successfully care at home, thus improving end-of-life experiences for families as
      a whole.

PMID- 25991567
TI  - Therapeutic Education in Improving Cancer Pain Management: A Synthesis of
      Available Studies.
AB  - This literature review aims to synthesize available studies and to update
      findings in order to obtain a current, comprehensive estimate of the benefits of
      pain education. Forty-four original articles obtained from the PubMed database
      were analyzed to investigate which protocols could be most effective in improving
      pain management. Recent studies indicate a growing interest in evaluating
      patients' skills and attitudes; these include satisfaction with cancer pain
      treatment, patient-reported improvement, and patient participation-all of which
      could be dependable benchmarks for evaluating the effectiveness of educational
      programs. Besides pain measurement, recent studies advance support for the
      importance of assessing newly developed outcome criteria. In this sense,
      patients' active participation and decision making in their pain management are
      probably the most relevant goals of pain education. 

PMID- 25991568
TI  - Medication Needs Vary for Terminally Ill Vietnam Era Veterans With and Without a
      Diagnosis of PTSD.
AB  - This retrospective pilot study aims to evaluate the clinical impact of palliative
      care in the treatment of terminally ill Vietnam Veterans with a history of
      posttraumatic stress disorder (PTSD) versus those without PTSD, as it pertains to
      medications for symptom control at the end of life (EOL). Active prescriptions
      for benzodiazepines, hypnotics, antidepressants, and antipsychotic medications at
      the EOL were recorded. During EOL care, 28 (72%) participants with PTSD used
      these medications versus 55 (40%) of the non-PTSD participants (P = .0005). There
      was significant correlation between a lifetime diagnosis of PTSD with
      antidepressant use (P = .0002) and hypnotics (P = .0085) during EOL care but not
      with benzodiazepines or antipsychotics. The higher utilization of certain
      medication classes among participants with PTSD may indicate that PTSD treatment
      should continue at the EOL to improve care. 

PMID- 25991569
TI  - Relationship Between Emotional Behavior in Mice and the Concentration of (+)
      alpha-Santalol in the Brain.
AB  - We previously reported finding anxiolytic-like activity for sandalwood oil after
      administration in mice. In this report, we further investigated the emotional
      behavior associated with inhaled or intraperitoneally administered (+)-alpha
      santalol, the main component of sandalwood oil, in addition to examining whether
      pharmacological or neurological transfers are responsible for this behavior.
      After administration of (+)-alpha-santalol by inhalation or intraperitoneal
      injection, we assessed anxiolytic-like and locomotor activities using elevated
      plus maze tests. We also examined the relationship between the emotional behavior
      and the (+)-alpha-santalol brain concentration. Anxiolytic-like activity was not
      observed immediately after administration or after water-immersion stress for 24
      h for either the (+)-alpha-santalol 2 MUL/L air inhalation or the (+)-alpha
      santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)-alpha
      santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the
      locomotor activity after exposure to water-immersion stress for 24 h. The brain
      (+)-alpha-santalol concentration was 2.6 ug/g tissue after (+)-alpha-santalol
      0.03 mL/kg (i.p.) administration. The observed shift of (+)-alpha-santalol to the
      brain suggests that this component acts via pharmacological transfer and is
      responsible for the sedative effect but not the anxiolytic-like activity.

PMID- 25991570
TI  - Sedation and Anesthesia in Pediatric and Congenital Cardiac Catheterization: A
      Prospective Multicenter Experience.
AB  - Sedation/anesthesia is critical to cardiac catheterization in the
      pediatric/congenital heart patient. We sought to identify current
      sedation/anesthesia practices, the serious adverse event rate related to airway,
      sedation, or anesthesia, and the rate of intra-procedural conversion from
      procedural sedation to the use of assisted ventilation or an artificial airway.
      Data from 13,611 patients who underwent catheterization at eight institutions
      were prospectively collected from 2007 to 2010. Ninety-four (0.69 %) serious
      sedation/airway-related adverse events occurred; events were more likely to occur
      in smaller patients (<4 kg, OR 4.4, 95 % CI 2.3-8.2, p < 0.001), patients with
      non-cardiac comorbidities (OR 1.7, 95 % CI 1.1-26, p < 0.01), and patients with
      low mixed venous oxygen saturation (OR 2.3, 95 % CI 1.4-3.6, p < 0.001). Nine
      thousand three hundred and seventy-nine (69 %) patients were initially managed
      with general endotracheal anesthesia, LMA, or tracheostomy, whereas 4232 (31 %)
      were managed with procedural sedation without an artificial airway, of which 75
      (1.77 %) patients were converted to assisted ventilation/general anesthesia.
      Young age (<12 months, OR 5.2, 95 % CI 2.3-11.4, p < 0.001), higher-risk
      procedure (category 4, OR 10.1, 95 % CI 6.5-15.6, p < 0.001), and continuous
      pressor/inotrope requirement (OR 11.0, 95 % CI 8.6-14.0, p < 0.001) were
      independently associated with conversion. Cardiac catheterization in
      pediatric/congenital patients was associated with a low rate of serious
      sedation/airway-related adverse events. Smaller patients with non-cardiac
      comorbidities or low mixed venous oxygen saturation may be at higher risk.
      Patients under 1 year of age, undergoing high-risk procedures, or requiring
      continuous pressor/inotrope support may be at higher risk of requiring conversion
      from procedural sedation to assisted ventilation/general anesthesia.

PMID- 25991571
TI  - Recombinant Tissue Plasminogen Activator in the Treatment of Neonates with
      Intracardiac and Great Vessels Thrombosis.
AB  - Life-threatening intracardiac and great vessels thrombi are rare in neonates.
      Recombinant tissue plasminogen activator (rTPA) is used in adults to stimulate
      fibrinolysis and facilitate thrombus resolution. Its use in neonates, along with
      heparin, remains controversial because of potential risk of serious bleeding. We
      aim to present our experience with the use of thrombolytic agents in seven
      neonates and young infants. In a retrospective study, over a period of 6 years,
      the medical records of neonates and young infants, who were diagnosed with
      intracardiac and great vessels thrombi, were reviewed. The following factors were
      collected: demographic data, primary diagnosis, thrombus site, risk factors,
      method of diagnosis, thrombolytic and/or anticoagulation agent, route, dose and
      duration of treatment, complications, and outcome. Six neonates and one 45-day
      old infant were analyzed. Age ranged from 5 to 45 days (median age 12 days), and
      median weight was 2.9 kg (range 0.9-3.8 kg). The thrombi were diagnosed by
      echocardiography in five and by angiography in two cases. All patients had life
      threatening thrombi; four were treated with rTPA (0.5 mg kg(-1) h(-1)) and
      heparin infusions with complete dissolution of the thrombi, within a median time
      of 60 h (6-72 h), and without complications. The remaining three patients (two
      who were premature, at 28 and 34 weeks of gestation, and the third who had a
      deranged coagulation profile) were treated with unfractionated heparin due to
      fear of bleeding. The thrombi dissolved in the premature babies (within 2 weeks
      and 3 months, respectively) but embolized and resulted in the death of the third
      infant after 2 weeks of treatment. The current case series confirmed the
      effectiveness and safety of intravenous rTPA infusion, at the dosages used, in
      neonates and young infants with life-threatening thrombi. 

PMID- 25991572
TI  - Tissue Doppler Imaging as a Predictor of Immunoglobulin Resistance in Kawasaki
      Disease.
AB  - Kawasaki disease (KD) is characterized by myocarditis and left ventricular
      dysfunction during the acute phase of the illness. Despite treatment with
      intravenous immunoglobulin (IVIG), a significant number of patients are IVIG
      resistant. We evaluated KD patients in the acute phase of illness using tissue
      Doppler imaging (TDI) to assess whether myocardial dysfunction may predict IVIG
      resistance. All patients with acute KD presenting to Children's Hospital Colorado
      from February 2007 through March 2014 were included in this study and underwent
      echocardiograms with TDI evaluation at diagnosis. Patients were divided into two
      groups: IVIG resistant and IVIG responder. Group differences were assessed using
      Wilcoxon-Mann-Whitney and Chi-square testing. Receiver operating characteristic
      (ROC) curve analysis was utilized to determine threshold values of TDI
      measurements associated with IVIG resistance. Fifty-one age-matched IVIG
      resistant patients were compared to 51 IVIG responder patients [median age, IQR
      44.57 (20.13-77.07) vs. 33.49 (17.30-62.89) months, p < 0.44]. There were
      significant differences in the septal and mitral early diastolic velocities (E')
      (p < 0.001 and p < 0.01), respectively. ROC analysis demonstrated that tricuspid
      E' <0.15 cm/s, septal E' <0.12 cm/s, and mitral E' <0.16 cm/s were good
      predictors of IVIG unresponsiveness (AUC = 0.66, 0.66, and 0.70, respectively).
      There were no differences between the systolic velocities and late diastolic
      velocities (A'). IVIG resistant KD patients present with significantly greater
      diastolic dysfunction compared to responders in patients with KD. TDI may be a
      useful tool to differentiate KD patients at higher risk of IVIG resistance. 

PMID- 25991573
TI  - Left circumflex artery aneurysm: the end-to-end reconstruction.
AB  - This report describes a surgical myocardial revascularization procedure for a
      huge, atherosclerotic left circumflex coronary artery aneurysm. The technique
      proposed in this paper is based on the isolation of the aneurysm followed by the
      aneurysmectomy and a complete reconstruction of the circumflex artery by an end
      to-end anastomosis. 

PMID- 25991574
TI  - The Potential of Cr3 [Triaqua-MU3 -Oxo-Hexa-MU-Propionatotrichromium(III)
      Chloride] to Reduce Birth Defects in the Offspring of Diabetic CD-1 Mice.
AB  - Diabetes mellitus is a growing concern worldwide and leads to multiple
      complications during pregnancy. Pharmacologic doses of chromium (Cr) have been
      linked with improving insulin sensitivity and other positive benefits in the
      treatment of diabetes in animal models. By using streptozotocin induced
      hyperglycemia in female CD-1 mice, reproductive outcomes of diabetic and chromium
      dosed diabetic females were examined. After dosing 10 mg/kg Cr in the form of
      triaqua-MU3 -oxo-hexa-MU-propionatotrichromium(III) chloride or Cr3 during
      gestation days 8-16 (GD8-GD16), all females were sacrificed on gestation day 17
      (GD17) and examined for maternal weight gain. The fetuses were examined for gross
      malformations and for skeletal malformations. The offspring of Cr3-dosed females
      tended to have a reduction in the incidence of supernumerary ribs. While
      hyperglycemia still had negative impacts on the health of dams and their
      offspring, administration of Cr led to an apparent trend in the reduction in the
      number of malformations and incidence of supernumerary ribs compared to those of
      untreated diabetic mothers. 

PMID- 25991575
TI  - Left ventricular twist and torsion: research observations and clinical
      applications.

PMID- 25991577
TI  - Re: Completely Intracorporeal Robotic-assisted Laparoscopic Augmentation
      Enterocystoplasty With Continent Catheterizable Channel (Urology 2014;84:1314
      1318).

PMID- 25991576
TI  - Effect of Detrusor Overactivity on Functional Outcomes After Holmium Laser
      Enucleation of the Prostate in Patients With Benign Prostatic Obstruction.
AB  - OBJECTIVE: To investigate the effect of detrusor overactivity (DO) on functional
      outcomes after holmium laser enucleation of the prostate (HoLEP). MATERIALS AND
      METHODS: One hundred ten men with benign prostatic obstruction were evaluated
      retrospectively. International Prostate Symptom Score, International Continence
      Society male questionnaire short form, 3-day voiding diary, and uroflowmetry with
      postvoid residual were evaluated preoperatively and at 3 and 6 months
      postoperatively. The patients underwent urodynamic study preoperatively and were
      divided into the DO group (58 of 110, 52.7%) and the non-DO group (52 of 100,
      47.3%). RESULTS: Patients in the DO group were older than those in the non-DO
      group (71.4 vs 66.4 years), although prostate volume and degree of obstruction
      were not significantly different between the 2 groups. All International Prostate
      Symptom Score and uroflowmetry parameters improved significantly at the 3- and 6
      month follow-ups. Storage symptoms in both groups were comparable preoperatively
      (9.7 vs 8.6); these improved similarly in both groups during follow-up (5.0 vs
      4.0, 6-month follow-up). The number of patients taking anticholinergics increased
      significantly after HoLEP, from a baseline of 17 patients to 49 patients at the 3
      month follow-up and 39 at the 6-month follow-up. More patients in the DO group
      were taking anticholinergics at the end of the follow-up period (48.3% vs 21.2%).
      CONCLUSION: Although the storage symptoms improved significantly in both groups,
      a significant number of patients with DO group took anticholinergics after HoLEP.
      We recommend that surgeons should counsel the possibility of taking
      anticholinergics in the early postoperative period to the patients with DO at
      baseline.

PMID- 25991578
TI  - Cumulative Review of Thrombotic Microangiopathy, Thrombotic Thrombocytopenic
      Purpura, and Hemolytic Uremic Syndrome Reports with Subcutaneous Interferon beta
      1a.
AB  - INTRODUCTION: Rare cases of thrombotic microangiopathy (TMA), manifested as
      thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS),
      have been reported with interferon beta products. We performed a cumulative
      review of TMA cases recorded in a Global Safety Database for patients with
      multiple sclerosis who received subcutaneous interferon beta-1a treatment.
      METHODS: Search criteria were: all reported cases, serious and non-serious, from
      all sources (including non-health care professionals and clinical trial reports),
      regardless of event ranking and causality assessment by reporter or company. Data
      lock was May 3, 2014, with additional analysis of cases reported between August
      1, 2014-November 30, 2014. RESULTS: Ninety-one patient cases (76.9% female) with
      105 events were retrieved. Time to onset varied from 2 months to 14 years, and in
      31.9% of patients the event occurred within 2 years of treatment initiation.
      Seven patients had a fatal outcome (five were secondary to other causes and two
      reported insufficient information). Forty-four patients recovered, 32 patients
      had not recovered at the time of the report, and in eight cases outcome was
      either not reported or unknown. Treatment was discontinued in 84.6% (77/91) of
      patients. In 67% (61/91) of patients, the reporter suspected a causal association
      between treatment and TMA/TTP-HUS. Risk factors and/or confounding factors were
      present in 45.1% (41/91) of patients. Early prodromal syndrome or specific
      patterns were not detected, although 54.9% (50/91) of cases contained
      insufficient information. Overall reporting rate of TMA/TTP-HUS was estimated as
      7.2 per 100,000 patient-years. Reporting rates for human serum album (HSA)
      containing and HSA-free formulations were 5.72 and 7.68 per 100,000 patient
      years, respectively. CONCLUSION: No new signal relating specifically to increased
      frequency of TMA/TTP-HUS with HSA-free subcutaneous interferon beta-1a was
      detected and no additional risk mitigation measures are required regarding the
      different formulations. The benefit-risk balance of subcutaneous interferon beta
      1a remains positive, and routine pharmacovigilance monitoring is appropriate.
      FUNDING: Ares Trading SA, Aubonne, Switzerland, a subsidiary of Merck Serono SA.

PMID- 25991579
TI  - Impact of the MLL1 morphemes on codon utilization and preservation in CpG
      islands.
AB  - Previous studies have shown that Mixed Lineage Leukemia 1 (MLL1 or MLL) binds a
      group of CpG-rich motifs known as morphemes. To examine whether occurrences of
      MLL1 morphemes in genomic DNA may influence codon utilization, we analyzed the
      frequency of various 9-mers in human cDNAs and in total human genomic DNA. We
      uncovered preferential utilization of GGC for Gly, GCG for Ala, CCG for Pro, and
      TCG for Ser, in coding sequences (CDSs) that included MLL1 morphemes. We also
      examined weighted occurrences of CDS 9-mers in a 30-base window that moved along
      each human chromosome. In plots, we observed peaks with fluctuating intensities.
      High intensity peaks appeared within promoter and exons localized in CpG islands,
      encompassing sequences that included MLL1 morphemes. High intensity peaks
      included CCG/GGC repeats, whose expansion may cause neurological disorders and
      congenital malformations. Such repeats are generated from overlap of a morpheme
      (CGCCG/CGGCG), which depending on reading frame and orientation would produce
      runs of Ala, Gly, or Pro in proteins. Overall, our results point to a role for
      morpheme occurrences on synonymous codon utilization in human genomic DNA and
      indicate that regulatory instructions are dispersed not only in promoters but
      also in exons of human genes.

PMID- 25991580
TI  - Cardiac perfusion imaging using hyperpolarized (13)C urea using flow sensitizing
      gradients.
AB  - PURPOSE: To demonstrate the feasibility of imaging the first passage of a bolus
      of hyperpolarized (13)C urea through the rodent heart using flow-sensitizing
      gradients to reduce signal from the blood pool. METHODS: A flow-sensitizing
      bipolar gradient was optimized to reduce the bright signal within the cardiac
      chambers, enabling improved contrast of the agent within the tissue capillary
      bed. The gradient was incorporated into a dynamic golden angle spiral (13)C
      imaging sequence. Healthy rats were scanned during rest (n = 3) and under
      adenosine stress-induced hyperemia (n = 3). RESULTS: A two-fold increase in
      myocardial perfusion relative to rest was detected during adenosine stress
      induced hyperemia, consistent with a myocardial perfusion reserve of two in
      rodents. CONCLUSION: The new pulse sequence was used to obtain dynamic images of
      the first passage of hyperpolarized (13)C urea in the rodent heart, without
      contamination from bright signal within the neighboring cardiac lumen. This probe
      of myocardial perfusion is expected to enable new hyperpolarized (13)C studies in
      which the cardiac metabolism/perfusion mismatch can be identified. Magnetic
      Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance.

PMID- 25991581
TI  - Successful treatment of subcorneal pustular dermatosis with maxacalcitol.

PMID- 25991582
TI  - Gold atomic clusters extracting the valence electrons to shield the carbon
      monoxide passivation on near-monolayer core-shell nanocatalysts in methanol
      oxidation reactions.
AB  - Atomic-scale gold clusters were intercalated at the inter-facet corner sites of
      Pt-shell Ru-core nanocatalysts with near-monolayer shell thickness. We
      demonstrated that these unique clusters could serve as a drain of valence
      electrons in the kink region of the core-shell heterojunction. As jointly
      revealed by density functional theory calculations and valence band spectra,
      these Au clusters extract core-level electrons to the valence band. They prevent
      corrosion due to protonation and enhance the tolerance of CO by increasing the
      electronegativity at the outermost surface of the NCs during the methanol
      oxidation reaction (MOR). In these circumstances, the retained current density of
      Pt-shell Ru-core NCs is doubled in a long-term (2 hours) MOR at a fixed voltage
      (0.5 V vs. SCE) by intercalating these sub-nanometer gold clusters. Such novel
      structural confinement provides a possible strategy for developing direct
      methanol fuel cell (DMFC) modules with high power and stability. 

PMID- 25991583
TI  - Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain
      metastases receiving vemurafenib in the real-world setting.
AB  - Brain metastases are a common and serious complication among patients with
      metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated
      clinical efficacy in patients with BRAF V600E-mutant melanoma brain metastases
      (MBM). We examined the real-world application and clinical outcomes of
      vemurafenib in this patient population. Demographic, treatment patterns,
      response, and survival data were collected from medical charts. Clinical data on
      283 patients with active BRAF V600E-mutant MBM treated with vemurafenib were
      provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5%
      had ECOG performance status of 0-1, and 43.1% used corticosteroids at vemurafenib
      initiation. Median follow-up was 5.7 months. Following vemurafenib initiation,
      48.1% of patients experienced intracranial response and 45.6% experienced
      extracranial response. The Kaplan-Meier estimate for overall survival was 59% at
      12 months. Multivariate analyses showed associations between intracranial
      response and both corticosteroid use and vemurafenib as initial therapy after MBM
      diagnosis. Larger size (5-10 mm vs. < 5 mm) and number of brain metastases (>= 5
      vs. < 2) and progressive extracranial disease at treatment initiation were
      associated with decreased intracranial response and increased risk of disease
      progression. Multiple extracranial sites (2 vs. < 2) and the absence of local
      treatments were also associated with increased risk of progression. Increased
      risk of death was associated with >= 2 extracranial disease sites, progressive
      extracranial disease, and >= 5 brain metastases. Subgroups of MBM patients may
      derive more benefit with vemurafenib, warranting prospective investigation.

PMID- 25991584
TI  - Coherent perfect absorption in deeply subwavelength films in the single-photon
      regime.
AB  - The technologies of heating, photovoltaics, water photocatalysis and artificial
      photosynthesis depend on the absorption of light and novel approaches such as
      coherent absorption from a standing wave promise total dissipation of energy.
      Extending the control of absorption down to very low light levels and eventually
      to the single-photon regime is of great interest and yet remains largely
      unexplored. Here we demonstrate the coherent absorption of single photons in a
      deeply subwavelength 50% absorber. We show that while the absorption of photons
      from a travelling wave is probabilistic, standing wave absorption can be observed
      deterministically, with nearly unitary probability of coupling a photon into a
      mode of the material, for example, a localized plasmon when this is a
      metamaterial excited at the plasmon resonance. These results bring a better
      understanding of the coherent absorption process, which is of central importance
      for light harvesting, detection, sensing and photonic data processing
      applications. 

PMID- 25991585
TI  - MicroRNA-409-3p suppresses colorectal cancer invasion and metastasis partly by
      targeting GAB1 expression.
AB  - Colorectal cancer (CRC) is one of the most common cancers worldwide and its
      metastasis accounts for the majority of deaths. However, the molecular mechanisms
      underlying CRC progression are not well characterized. In this study, we
      identified miR-409-3p as a tumor suppressor of CRC. MiR-409-3p expression was
      significantly downregulated in CRC tissue compared to adjacent non-tumor tissue,
      and reduced miR-409-3p expression was correlated with CRC metastasis. In vitro
      and in vivo studies revealed that miR-409-3p negatively regulated CRC metastatic
      capacities, including suppressing cancer cell migration, invasion and metastasis.
      To explore the mechanism of action of miR-409-3p, we adopted a pathway and
      pathophysiological event-based target screening and validation approach, and
      found nine known metastasis-related genes as potential targets. The 3'-UTR
      binding assays between the candidates and miR-409-3p suggested that only GAB1,
      NR4A2 and LMO4 were directly regulated by the miRNA. However, endogenous
      expression analysis revealed that only GAB1 was modulated by miR-409-3p in CRC
      cells at both the mRNA and protein levels. Furthermore, we provided evidence to
      conclude that GAB1 was partially responsible for miR-409-3p-mediated metastasis.
      Taken together, our data demonstrate that miR-409-3p is a metastatic suppressor,
      and post-transcriptional inhibition of the oncoprotein GAB1 is one of the
      mechanisms of action of this miRNA. Our finding suggests miR-409-3p might be a
      novel target for CRC metastasis treatment. 

PMID- 25991586
TI  - Implementation and outcomes of a pharmacy residency mentorship program.
AB  - PURPOSE: The implementation and outcomes of a pharmacy residency mentorship
      program are described. SUMMARY: The mentorship program at the Detroit Medical
      Center was formally implemented during the residency orientation period in 2013.
      Residents had up to two months after the start of the residency to choose a
      mentor, which we believed was an adequate amount of time to meet all members of
      the department of pharmacy. One year after implementation of the mentorship
      program, an anonymous survey was administered to all 16 residents to gather
      feedback about the mentorship program. Eleven (70%) of the 16 residents completed
      the survey. A majority agreed that having a mentor was a beneficial aspect of
      their residency training, often citing their mentor as integral in their career
      planning and helpful in balancing their personal and professional lives. Further,
      91% (n = 10) of the respondents indicated that they planned on remaining in
      contact with their mentor after their residency. Nearly half of the residents met
      multiple times per month or weekly. All respondents stated that their mentor was
      available and accessible when needed. The year after program implementation, all
      residents were either offered a position for employment or matched to a residency
      before the completion of the residency. Although the mentors were not assessed
      with an anonymous survey, there continues to be overwhelming support for the
      continuation and improvement of the program as part of residency training.
      CONCLUSION: Implementation of a mentorship program during residency training was
      viewed as beneficial for personal and professional development by many of the
      residents.

PMID- 25991587
TI  - Pharmacotherapy for posttraumatic stress disorder at a Veterans Affairs facility.
AB  - PURPOSE: Results of a study of psychotropic prescribing patterns in a Veterans
      Affairs (VA) population with posttraumatic stress disorder (PTSD) are presented.
      METHODS: VA prescription records were reviewed to identify veterans with PTSD at
      a large VA healthcare center and evaluate their medication regimens for
      conformance with a VA practice guideline that calls for the use of selective
      serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake
      inhibitors (SNRIs) as first-line therapies for PTSD; the VA guideline does not
      recommend second-generation antipsychotics (SGAs) and benzodiazepines for PTSD
      symptom control. The primary objective was to determine if veterans with PTSD who
      were receiving an SGA had first received SSRI or SNRI therapy in accordance with
      VA recommendations. RESULTS: Among 308 veterans who met the inclusion criteria,
      the average number of SSRI or SNRI agents prescribed prior to initiation of SGA
      therapy was 0.88. Only 19.8% of patients (n = 61) had been prescribed 2 SSRI or
      SNRI agents, with 48.4% of patients (n = 149) having received 1 agent. All
      evaluated courses of SSRI and SNRI therapy prior to SGA initiation were of
      sufficient duration (range, 5-30 months), and mean adherence rates were >80%.
      Current or past benzodiazepine use was documented in about 55% of patients (n =
      170). CONCLUSION: SSRIs and SNRIs were under-utilized for the treatment of PTSD
      at the study site in patients receiving an SGA. The current use of
      benzodiazepines in these patients was lower than a reported national average for
      VA patients.

PMID- 25991588
TI  - Residency application screening tools: A survey of academic medical centers.
AB  - PURPOSE: The current use and content of screening tools utilized by ASHP
      accredited pharmacy residency programs were assessed. METHODS: A survey
      consisting of 19 questions assessing residency programs and the screening of
      pharmacy residency program applicants was e-mailed to residency directors of 362
      pharmacy residency programs at 105 University HealthSystem Consortium (UHC)
      member institutions. Questions gathered general program demographic information,
      data related to applicant growth from residency years 2010-11 to 2011-12, and
      information about the residency screening processes currently used. RESULTS:
      Responses were received from 73 residency program sites (69.5%) of the 105 UHC
      member institutions to whom the e-mail was sent. Many sites used screening tools
      to calculate applicants' scores and then determined which candidates to invite
      for an onsite interview based on applicants' scores and group discussion. Seventy
      eight percent (n = 57) of the 73 responding institutions reported the use of a
      screening tool or rubric to select applicants to invite for onsite interviews.
      The most common method of evaluation was individual applicant review before
      meeting as a group to discuss candidate selection. The most important factor for
      determining which residency candidate to interview was the overall impression
      based on the candidate's curriculum vitae (CV) and letters of recommendation.
      CONCLUSION: Most residency programs in UHC-member hospitals used a screening tool
      to determine which applicants to invite for an onsite interview. The most
      important factor for determining which residency candidate to interview was the
      overall impression based on the candidate's CV and letters of recommendation.

PMID- 25991589
TI  - Using active methicillin-resistant Staphylococcus aureus surveillance nasal swabs
      to predict clinical respiratory culture results.
AB  - PURPOSE: Results of a study to determine the utility of methicillin-resistant
      Staphylococcus aureus (MRSA) active surveillance via nasal-swab screening in
      predicting the results of clinical respiratory cultures are reported. METHODS: A
      retrospective chart review-based descriptive analysis was conducted at a Veterans
      Affairs (VA) medical center. VA databases were used to identify adult patients
      admitted to the facility over a one-year period who underwent both respiratory
      culture testing and active MRSA surveillance nasal-swab screening during the
      hospitalization; only data on patients who had a MRSA surveillance swab within 48
      hours before or after respiratory culture testing were included in the analysis.
      The sensitivity, specificity, and positive and negative predictive values of the
      MRSA screening method were calculated. RESULTS: Data on a total of 297
      respiratory cultures and corresponding nasal-swab results were reviewed. The
      positive predictive value of the nasal-swab method of MRSA surveillance screening
      was calculated as 37.5% (95% confidence interval [CI], 21.1-56.3%); the negative
      predictive value was 99.3% (95% CI, 97.3-99.9%). MRSA screening by nasal swab had
      a calculated specificity of 92.9% (95% CI, 89.3-95.6%) and sensitivity of 87.5%
      (95% CI, 57.2-98.2%). Using Fisher's exact test, it was determined that there was
      a significant association between swab and culture results (p < 0.001).
      CONCLUSION: This analysis demonstrated a notable association between negative
      results of nasal-swab screening for MRSA and an absence of MRSA growth on
      respiratory clinical cultures at the study site, suggesting that airway swab
      screening can be a useful tool for streamlining antimicrobial therapy.

PMID- 25991590
TI  - Comparison of acute renal injury associated with intermittent and extended
      infusion piperacillin/tazobactam.
AB  - OBJECTIVE: The purpose of this study is to compare the incidence of acute renal
      injury (ARI) in patients on intermittent infusion to extended infusion
      piperacillin/tazobactam. METHODS: Data was collected for the intermittent
      infusion group from November 2010 to December 2010 until 100 patients were
      enrolled. The data was then compared to 100 patients in the extended infusion
      group from November 2011 to December 2011. Patients who received at least three
      consecutive doses of piperacillin/tazobactam and were inpatient for at least 48
      hours were included. Patients were excluded for any of the following: baseline
      serum creatinine (SCr) >=4 mg/dL, age less than 18 years old, pregnancy,
      penicillin allergy, or concurrent use with any cephalosporin or penicillin. The
      primary endpoint was the incidence of ARI, defined as a SCr two times the
      baseline or 0.5 mg/dL increase within 24 hours. The secondary endpoint was
      patient length of stay, measured as actual inpatient days. RESULTS: Eleven
      patients in the intermittent infusion group and nine patients in the extended
      infusion group developed ARI (11% vs. 9%, p = 0.637). The length of stay between
      the intermittent and extended infusion groups was 19 days vs. 14 days,
      respectively (p = 0.083). CONCLUSION: The incidence of ARI in patients on
      piperacillin/tazobactam was similar between the intermittent and extended
      infusion groups. Larger studies should be considered to confirm that the
      incidence of ARI associated with piperacillin/tazobactam is not infusion-related.

PMID- 25991591
TI  - Impact of pharmacist-managed warfarin on patient outcomes in an academic medical
      center.

PMID- 25991592
TI  - Pharmacist involvement in optimizing discharge care of hospitalized patients.

PMID- 25991593
TI  - Strategies for successfully navigating the pharmacy residency interview process.
AB  - The residency interview process is an exciting, stressful, whirlwind experience.
      Suggestions for optimizing this experience include: maintaining a professional
      presence, arriving on-time, being collegial with your co-applicants, judicious
      use of your cell phone, preparation of questions to ask and responses to
      questions asked of you, and sending thank-you notes. While these suggestions may
      sound intuitive, in the heat of the moment it is possible to make a crucial
      interview faux pas. Thinking through these issues ahead of time and proactively
      planning for your interview experience will help you to be calm, confident, and
      poised for success during your interview. 

PMID- 25991594
TI  - Impact of pharmacist intervention in conjunction with outpatient physician follow
      up visits after hospital discharge on readmission rate.
AB  - OBJECTIVE: The Medicare Hospital Readmissions Reduction Program (MHRRP) which
      took effect on October 1st, 2012 holds providers accountable for quality of care
      delivered, placing a greater focus on care coordination. Innovative strategies in
      medication management in the acute care and outpatient primary care settings
      require vigilant pharmacist intervention. The objective of this study is to
      determine if pharmacist-provided medication reconciliation service in conjunction
      with hospital follow-up outpatient physician visits reduces hospital readmission
      rate. METHODS: This was a prospective study in which physician-initiated
      outpatient hospital follow-up appointment scheduling was used to identify
      patients at time of hospital discharge. All patients >=50 years of age were
      eligible for outpatient pharmacist visits. Emergency room visits were excluded.
      Data collected included: patient demographics, characteristics of identified drug
      therapy problems, accuracy of outpatient medication histories and time required
      by pharmacist to perform the reviews. Patient adherence to early (24-72 hours)
      outpatient hospital follow-up visit was also evaluated. Previous year's
      readmission data for high risk patients who received only physician visits were
      also collected for comparison with those who were jointly visited by pharmacists
      and physicians. RESULTS: A total of 98 patients were assigned to receive
      pharmacist intervention in conjunction with physician hospital follow-up visits.
      Nine of the 98 patients seen by pharmacists at hospital follow-up visits were
      readmitted (9.2%) to a hospital within 30 days of discharge. Out of the 236
      patients seen during the same period the previous year (2011) for physician alone
      hospital follow-up visits 46 were readmitted (19.4%) within 30-days of hospital
      discharge. The difference between these groups was statistically significant (p =
      0.023), with patients in the pharmacist intervention group experiencing a
      reduction in 30-day readmission risk. Physician alone outpatient follow-up was
      associated with earlier mean time to readmission, 12.8 days vs. 18.3 days in the
      pharmacist intervention group (p = 0.042). CONCLUSION: Pharmacist involvement in
      hospital discharge follow-up visits reduced overall readmission rate in high risk
      patients and improved monitoring of drug therapy, and medication history accuracy
      when compared to physician-alone visits.

PMID- 25991595
TI  - Implementing a pharmacy resident run transition of care service for heart failure
      patients: Effect on readmission rates.
AB  - OBJECTIVE: Heart failure (HF) is a leading cause of hospital readmissions
      adversely affecting resources and hospital reimbursements. The purpose of this
      study was to optimize medication therapy, provide patient education and
      facilitate discharge and follow-up through the creation of a pharmacy resident
      managed HF transition service with the intention of decreasing readmission rates.
      METHODS: A 6-month prospective, single center pilot study was conducted by a
      pharmacy resident to decrease readmission rates in patients with HF. Patients
      were identified through emergency department admission reports and direct
      requests from discharge nurses. The pharmacy resident provided patients with
      tailored medication and disease state counseling, ensured obtainment of discharge
      medications and performed follow up telephone calls for appointment reminders and
      further counseling. The primary outcome measured was readmission rate at 30 days.
      Secondary outcomes were number of patients requesting safety net medications,
      reason for readmission(s), and appointment compliance. RESULTS: Thirty patients
      were enrolled in the program. The 30-day heart failure readmission rate decreased
      from 28.1% to 16.6%. Eighty-eight percent of patients attended their follow up
      appointments. CONCLUSION: A reduction in readmission rate was achieved through
      this pharmacy resident-run HF transition service. The majority of patients
      attended follow-up visits and financial appointments after discharge.

PMID- 25991596
TI  - Effects of pharmacy resident led education on resident physician prescribing
      habits associated with stress ulcer prophylaxis in non-intensive care unit
      patients.
AB  - OBJECTIVE: Overutilization of stress ulcer prophylaxis in both critically and
      noncritically ill patients poses significant health risks and increases
      healthcare costs. The purpose of this study was to assess the impact of education
      for appropriate stress ulcer prophylaxis prescribing by Family Medicine Resident
      Physicians. METHODS: The study evaluated the SUP prescribing and continuation or
      discontinuation of acid suppressive therapy upon discharge. Patients admitted to
      the Family Medicine Residency team at Washington Regional Medical Center were
      retrospectively assessed from September through November 2011. In January 2012,
      an educational seminar describing appropriate stress ulcer prophylaxis
      indications, the associated risks and costs of acid suppressive therapy, and
      initial findings was provided. After the educational intervention, patients
      admitted to the Family Medicine Residency team were retrospectively followed from
      February through April 2012 to assess the impact of the educational intervention.
      RESULTS: Post education analysis demonstrated a decrease in inappropriate stress
      ulcer prophylaxis prescribing from 55.5% to 30.5% (p < 0.0001). There was no
      statistically significant difference between the pre-intervention (5.5%) and post
      intervention (8.3%) groups in regards to patients discharged on AST
      inappropriately (p = 0.627). CONCLUSION: Pharmacist led educational sessions
      improved appropriateness of stress ulcer prophylaxis prescribing by Family
      Practice Resident Physicians, leading to patient risk avoidance and cost
      savings..

PMID- 25991597
TI  - Increasing compliance with national quality measures for stroke through use of a
      standard order set.
AB  - PURPOSE: Results of a study to determine the impact of physician use of a
      medication order set on compliance with national quality standards for acute
      stroke treatment are presented. METHODS: The medical records of adult patients
      treated for ischemic stroke at three certified primary stroke centers within a
      large healthcare system were retrospectively reviewed to assess compliance with
      eight mandatory standards of care. Overall adherence to the standards and rates
      of compliance with individual standards were compared in random samples of
      patients treated with or without physician use of an order set providing guidance
      on acute stroke pharmacotherapy and other aspects of stroke management. RESULTS:
      Treatment records indicated use of the acute stroke order set in 58% of the 120
      patient cases reviewed. Individual patients who were treated without physician
      use of the order set were more than twice as likely as those in the comparator
      group to receive care that was not in compliance with at least one of the eight
      mandatory quality standards (odds ratio, 2.4; 95% confidence interval, 1.43-4.05;
      p < 0.001). Use of the order set was associated with significantly improved
      adherence to three standards: venous thromboembolism prophylaxis, stroke
      education, and statin therapy at discharge. CONCLUSION: A retrospective review of
      the treatment records of patients hospitalized for acute stroke showed that
      adherence to national guidelines was increased when providers used a standard
      order set.

PMID- 25991598
TI  - The ABPI's response to news story on leading academics' condemnation of
      government undermining of NICE.

PMID- 25991599
TI  - Molecular profile of urothelial carcinoma of the upper urinary tract: are
      pelvicalyceal and ureteral tumors different?
AB  - PURPOSE: To assess the potential biologic impact of tumor location on oncological
      outcomes for patients with upper tract urothelial carcinoma (UTUC), we used
      prospectively collected molecular signatures of high-grade UTUC. METHODS:
      Immunohistochemical staining for p21, p27, p53, cyclin E, and Ki-67 was
      prospectively performed on 96 UTUC specimens of patients with non-metastatic high
      grade UTUC treated with extirpative surgery. Patients were grouped according to
      primary tumor location (pelvicalyceal vs. ureteral) where primary tumor was
      defined as the highest tumor stage and diameter. Primary outcome was assessment
      of differences in marker expression between groups. Secondary outcome was
      difference in survival according to marker status. RESULTS: Pelvicalyceal and
      ureteral tumors were found in 52.1 and 47.9 %, respectively, and 42.7 % of
      patients had non-organ-confined disease. Over a median follow-up of 22.0 months,
      31.2 and 20.8 % of patients experienced disease recurrence and died of UTUC,
      respectively. The total number of altered markers stained for was 0-2 in 67.7 and
      3-5 in 32.3 % of patients. The number of altered markers and alteration status of
      markers were not significantly different between patients with primary
      pelvicalyceal versus ureteral tumors when stratified by tumor stage and nodal
      status. There were no significant differences in survival outcomes between both
      groups when stratified by number of altered markers (0-2 and 3-5). CONCLUSIONS:
      The prospective assessment of selected cell cycle and proliferative markers
      suggests no molecular difference between UTUC of the pelvicalyceal system and
      that of the ureter. Our study is limited by its size and definition of location.

PMID- 25991600
TI  - Stress incontinence surgery at the time of prolapse surgery: mandatory or
      forbidden?
AB  - INTRODUCTION: Concomitant anti-incontinence surgery at the time of prolapse
      repair has been a long-debated topic. Still today, there remains no clear answer
      to this question, although in recent years the literature has become more robust
      with the addition of more randomized controlled trials. The lifetime risk for
      women of undergoing surgical correction of pelvic organ prolapse is significant,
      and concomitant anti-incontinence surgery is an important question during
      surgical planning. MATERIALS AND METHODS: This review delves further into the
      current literature to discuss a possible algorithm for managing the risk of
      stress incontinence after pelvic organ prolapse repair and examines the support
      in the literature for the following treatment methods: (1) anti-incontinence
      surgery for all women undergoing pelvic organ prolapse repair, (2) anti
      incontinence surgery for no women undergoing pelvic organ prolapse repair, and
      (3) anti-incontinence surgery in select women undergoing pelvic organ prolapse
      repair. CONCLUSIONS: While there are data both for and against each of these
      approaches, after a review of the literature, we recommend anti-incontinence
      surgery for select women undergoing pelvic organ prolapse repair, including women
      with a history of symptomatic and occult stress incontinence diagnosed
      preoperatively.

PMID- 25991601
TI  - Predictive factors for immediate continence after radical prostatectomy.
AB  - PURPOSE: To identify predictive factors for immediate continence after radical
      prostatectomy. PATIENTS AND METHODS: A total of 1553 patients underwent radical
      prostatectomy in a single institution (670 RRP, 883 RARP), had complete
      perioperative data and follow-up for urinary continence and were included in this
      prospective analysis. Immediate continence was defined as no pad usage after
      catheter removal. Evaluated parameters included age, body mass index, ECOG
      performance status, erectile function, prostate volume, PSA, Gleason score, tumor
      stage and D'Amico risk groups, as well as surgical approach (RRP, RARP), surgeon
      volume, nerve-sparing, lymphadenectomy, blood transfusions and duration of
      catheterization. RESULTS: A total of 240 men (15.5 %) did not require any pads 1
      day or later after removal of the transurethral catheter. Correlation of
      parameters with immediate continence revealed significance for age (p < 0.001),
      ECOG-score (p = 0.025), erectile function (p = 0.001), nerve-sparing (p = 0.022),
      Gleason score (p = 0.002) and surgeon volume (p <= 0.022). Multivariate analyses
      identified IIEF-score >21 (p = 0.031), ECOG (p < 0.05), bilateral nerve-sparing
      (p = 0.049), Gleason score <3 + 4 (p <= 0.028), less blood transfusion (p <=
      0.044) and surgeon volume (p <= 0.042) as the remaining prognostic parameters for
      immediate continence after radical prostatectomy. The type of surgical approach
      (robotic vs. open radical prostatectomy) did not yield significant influence.
      CONCLUSION: Evaluating continence in a contemporary prospective cohort revealed
      15.5 % of patients never requiring a pad postoperatively. Predictive parameters
      for immediate continence were erectile function, ECOG, bilateral nerve-sparing,
      less blood transfusion and Gleason score. Furthermore, the surgeon's experience
      but not his operative technique had a significant impact on immediate
      postoperative continence.

PMID- 25991602
TI  - Methodological Remarks Regarding the Meta-Analysis on Possible Associations of
      Maternal Factors During Pregnancy With the Risk of Childhood Acute Lymphoblastic
      Leukemia.

PMID- 25991603
TI  - INT (2-(4-Iodophenyl)-3-(4-Nitrophenyl)-5-(Phenyl) Tetrazolium Chloride) Is Toxic
      to Prokaryote Cells Precluding Its Use with Whole Cells as a Proxy for In Vivo
      Respiration.
AB  - Prokaryote respiration is expected to be responsible for more than half of the
      community respiration in the ocean, but the lack of a practical method to measure
      the rate of prokaryote respiration in the open ocean resulted in very few
      published data leaving the role of organotrophic prokaryotes open to debate.
      Oxygen consumption rates of oceanic prokaryotes measured with current methods may
      be biased due to pre-incubation size filtration and long incubation times both of
      which can change the physiological and taxonomic profile of the sample during the
      incubation period. In vivo INT reduction has been used in terrestrial samples to
      estimate respiration rates, and recently, the method was introduced and applied
      in aquatic ecology. We measured oxygen consumption rates and in vivo INT
      reduction to formazan in cultures of marine bacterioplankton communities, Vibrio
      harveyi and the eukaryote Isochrysis galbana. For prokaryotes, we observed a
      decrease in oxygen consumption rates with increasing INT concentrations between
      0.05 and 1 mM. Time series after 0.5 mM INT addition to prokaryote samples showed
      a burst of in vivo INT reduction to formazan and a rapid decline of oxygen
      consumption rates to zero within less than an hour. Our data for non-axenic
      eukaryote cultures suggest poisoning of the eukaryote. Prokaryotes are clearly
      poisoned by INT on time scales of less than 1 h, invalidating the interpretation
      of in vivo INT reduction to formazan as a proxy for oxygen consumption rates.

PMID- 25991605
TI  - Accumulation of murine amyloid-beta mimics early Alzheimer's disease.
AB  - Amyloidosis mouse models of Alzheimer's disease are generally established by
      transgenic approaches leading to an overexpression of mutated human genes that
      are known to be involved in the generation of amyloid-beta in Alzheimer's
      families. Although these models made substantial contributions to the current
      knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the
      overproduction of amyloid-beta peptides mimics only inherited (familiar)
      Alzheimer's disease, which accounts for <1% of all patients with Alzheimer's
      disease. The inherited form is even regarded a 'rare' disease according to the
      regulations for funding of the European Union (www.erare.eu). Here, we show that
      mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid
      beta-degrading enzyme, and the ABC transporter ABCC1, a major contributor to
      amyloid-beta clearance from the brain, develop various aspects of sporadic
      Alzheimer's disease mimicking the clinical stage of mild cognitive impairment.
      Using behavioural tests, electrophysiology and morphological analyses, we
      compared different ABC transporter-deficient animals and found that alterations
      are most prominent in neprilysin * ABCC1 double-deficient mice. We show that
      these mice have a reduced probability to survive, show increased anxiety in new
      environments, and have a reduced working memory performance. Furthermore, we
      detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis
      and reduced numbers of synapses, leading to defective long-term potentiation in
      functional measurements. Compared to human, murine amyloid-beta is poorly
      aggregating, due to changes in three amino acids at N-terminal positions 5, 10,
      and 13. Interestingly, our findings account for the action of early occurring
      amyloid-beta species/aggregates, i.e. monomers and small amyloid-beta oligomers.
      Thus, neprilysin * ABCC1 double-deficient mice present a new model for early
      effects of amyloid-beta-related mild cognitive impairment that allows
      investigations without artificial overexpression of inherited Alzheimer's disease
      genes.

PMID- 25991604
TI  - Loss of MT1-MMP causes cell senescence and nuclear defects which can be reversed
      by retinoic acid.
AB  - MT1-MMP (MMP14) is a collagenolytic enzyme located at the cell surface and
      implicated in extracellular matrix (ECM) remodeling. Mmp14(-/-) mice present
      dwarfism, bone abnormalities, and premature death. We demonstrate herein that the
      loss of MT1-MMP also causes cardiac defects and severe metabolic changes, and
      alters the cytoskeleton and the nuclear lamina structure. Moreover, the absence
      of MT1-MMP induces a senescent phenotype characterized by up-regulation of
      p16(INK4a) and p21(CIP1/WAF) (1), increased activity of senescence-associated
      beta-galactosidase, generation of a senescence-associated secretory phenotype,
      and somatotroph axis alterations. Consistent with the role of retinoic acid
      signaling in nuclear lamina stabilization, treatment of Mmp14(-/-) mice with all
      trans retinoic acid reversed the nuclear lamina alterations, partially rescued
      the cell senescence phenotypes, ameliorated the pathological defects in bone,
      skin, and heart, and extended their life span. These results demonstrate that
      nuclear architecture and cell senescence can be modulated by a membrane protease,
      in a process involving the ECM as a key regulator of nuclear stiffness under cell
      stress conditions.

PMID- 25991607
TI  - Testing Clinical Scores to Diagnose Incident Deep Vein Thrombosis in Patients
      Hospitalized in a Department of Medicine: Can Biomarkers Improve Accuracy?
AB  - Shifting the context from the emergency department to the department of medicine,
      we compared different scores to diagnose deep vein thrombosis (DVT) in patients
      with several comorbidities, hospitalized in a department of internal medicine. We
      prospectively recruited 178 consecutive hospitalized patients in whom clinical
      suspicion of DVT was assessed by Wells modified score for DVT, Hamilton, Kahn,
      and St Andre Hospital scores. Deep vein thrombosis was confirmed in 85 (48%)
      patients by both echocolor Doppler and angiocomputed tomography scan. The use of
      risk scores based on symptoms and clinical signs was weakly useful (area under
      the curve [AUC]: 0.69, positive predictive value: 59%, and negative predictive
      value: 74%). Patients with DVT had significantly (P < .0001) lower serum albumin
      and protein S levels compared to those without DVT. Moreover, serum protein S
      (AUC: 0.82) and albumin in percentage (AUC: 0.80) showed a better accuracy than
      clinical scores (P < .001) in assessing the diagnosis of DVT. Therefore, serum
      albumin and protein S improved the accuracy of clinical scores for the diagnosis
      of incident DVT in patients hospitalized in a department of medicine. 

PMID- 25991606
TI  - Robust and high resolution hyperpolarized metabolic imaging of the rat heart at 7
      T with 3D spectral-spatial EPI.
AB  - PURPOSE: Hyperpolarized metabolic imaging has the potential to revolutionize the
      diagnosis and management of diseases where metabolism is dysregulated, such as
      heart disease. We investigated the feasibility of imaging rodent myocardial
      metabolism at high resolution at 7 T. METHODS: We present here a fly-back
      spectral-spatial radiofrequency pulse that sidestepped maximum gradient strength
      requirements and enabled high resolution metabolic imaging of the rodent
      myocardium. A 3D echo-planar imaging readout followed, with centric ordered z
      phase encoding. The cardiac gated sequence was used to image metabolism in
      rodents whose metabolic state had been manipulated by being fasted, fed, or fed
      and given the pyruvate dehydrogenase kinase inhibitor dichloroacetate. RESULTS:
      We imaged hyperpolarized metabolites with a spatial resolution of 2*2*3.8 mm(3)
      and a temporal resolution of 1.8 s in the rat heart at 7 T. Significant
      differences in myocardial pyruvate dehydrogenase flux were observed between the
      three groups of animals, concomitant with the known biochemistry. CONCLUSION: The
      proposed sequence was able to image in vivo metabolism with excellent spatial
      resolution in the rat heart. The field of view enabled the simultaneous multi
      organ acquisition of metabolic information from the rat, which is of great
      utility for preclinical research in cardiovascular disease. Magnetic Resonance in
      Medicine published by Wiley Periodicals, Inc. on behalf of International Society
      for Magnetic Resonance.

PMID- 25991609
TI  - Editorial freedom assured.

PMID- 25991610
TI  - New technology means new patient role.

PMID- 25991608
TI  - Randomised clinical trial of snus versus medicinal nicotine among smokers
      interested in product switching.
AB  - BACKGROUND: An essential component of evaluating potential modified risk tobacco
      products is to determine how consumers use the product and resulting effects on
      biomarkers of toxicant exposure. STUDY DESIGN: Cigarette smokers (n=391)
      recruited in Minnesota and Oregon were randomised to either snus or 4 mg nicotine
      gum for 12 weeks. Participants were instructed to completely switch from
      cigarettes to these products. Urine samples were collected to analyse for
      carcinogenic tobacco-specific nitrosamine metabolites (4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol and N'-nitrosonornicotine and their glucuronides) and nicotine
      metabolites (total cotinine and nicotine equivalents) levels. RESULTS: Of the 391
      participants randomised, 52.9% were male, the mean+/-SD age was 43.9+/-12.5
      years, baseline number of cigarettes/day was 18.0+/-6.5 and Fagerstrom Test for
      Nicotine Dependence score was 5.1+/-2.0. The mean+/-SD number of snus pouches
      used/week at week 6 prior to tapering was 39.1+/-24.0 and nicotine gum pieces
      used was 37.6+/-26.3. Dual use of cigarettes and these products were observed in
      52.9% and 58.2% of those assigned to snus and nicotine gum, respectively, at week
      12. The end of treatment biochemically verified (carbon monoxide, CO<6 ppm) 7-day
      avoidance of cigarettes was 21.9% in the snus group and 24.6% in the nicotine gum
      group. Toxicant exposure in the nicotine gum group was significantly less when
      compared to snus. CONCLUSIONS: Snus performed similarly to nicotine gum in
      cigarette smokers who were interested in completely switching to these products,
      but was associated with less satisfaction and greater toxicant exposure than
      nicotine gum. TRIAL REGISTRATION NUMBER: NCT: 00710034.

PMID- 25991611
TI  - [Re: Staring death in the eye].

PMID- 25991614
TI  - [Re: A world free of nuclear weapons].

PMID- 25991615
TI  - [B. Hilt replies].

PMID- 25991619
TI  - [Correction: A young woman with slender hands].

PMID- 25991620
TI  - [Vaccination against the shingles].

PMID- 25991621
TI  - [Diffusion-weighted MR in transient ischemic attacks].

PMID- 25991623
TI  - Self-management of warfarin therapy.
AB  - BACKGROUND: Clinical studies from other countries show that self-management of
      warfarin therapy may reduce the risk of mortality, thromboembolism and
      complications when compared to conventional therapy. The purpose of this study
      was to train patients in self-management and compare the results with
      conventional therapy in Norway. METHOD: A total of 23 patients who had previously
      been given conventional therapy by their GPs were instructed in how to measure
      INR (using the CoaguChek XS device) and administer warfarin dosage through a
      structured training programme over the course of 27 weeks. The participants
      continued with self-management for a further 28 weeks after the end of the
      training period. The time in the therapeutic range (TTR, measured as a
      percentage) was calculated and the TTR for conventional therapy and self
      management were compared. RESULTS: No significant difference in average TTR was
      found when comparing conventional therapy (70% (95% confidence interval (CI) 62
      78)) with the self-management period (75% (95% CI 69-81, p = 0.24)). The
      percentage of extreme INR values (< 1.5 or > 5.0) was higher during conventional
      therapy than during self-management (6.8% vs. 1.0%, p < 0.001). INTERPRETATION:
      No significant difference in TTR was found when comparing self-management and
      conventional warfarin therapy in our study, but for self-management there was a
      lower percentage of extreme INR values compared to conventional warfarin therapy.

PMID- 25991624
TI  - Impact of the environment on multiple sclerosis.
AB  - BACKGROUND: Epidemiological studies suggest that environmental factors play a
      significant role in the development of multiple sclerosis. This article presents
      current knowledge on the impact of the environment on disease risk and disease
      course. METHOD: We have conducted searches in PubMed for "multiple sclerosis"
      combined with "environment" as well as relevant environmental factors. RESULTS:
      It is highly likely that an interaction between genetic and environmental factors
      determines who will develop multiple sclerosis. Epstein-Barr virus infection,
      smoking, and low vitamin D levels are the environmental factors that have shown
      the strongest and most consistent association with development of the disease.
      Low vitamin D levels are also associated with high disease activity. Other risk
      factors include obesity and high salt intake. INTERPRETATION: Although
      epidemiological studies have identified a number of environmental factors with
      potential aetiological relevance, and the importance of these is supported by
      experimental studies, there is still insufficient evidence to establish a causal
      role for these factors in multiple sclerosis.

PMID- 25991626
TI  - [Knee surgery fellowship in London].

PMID- 25991625
TI  - [A man in his 50s with colitis and facial palsy].

PMID- 25991627
TI  - [Thinking big].

PMID- 25991632
TI  - [Meeting yourself and others in the door].

PMID- 25991637
TI  - Hepatitis B Virus Screening for Patients With Cancer Before Therapy: American
      Society of Clinical Oncology Provisional Clinical Opinion Update.

PMID- 25991638
TI  - Redesigning Advanced Cancer Care Delivery: Three Ways to Create Higher Value
      Cancer Care.

PMID- 25991639
TI  - Use of Adjuvant Cisplatin-Based Versus Carboplatin-Based Chemotherapy in Non
      Small-Cell Lung Cancer: Findings From the Florida Initiative for Quality Cancer
      Care.
AB  - PURPOSE: For patients with resected non-small-cell lung cancer, national
      guidelines recommend cisplatin-based doublet chemotherapy as the preferred
      treatment. However, many patients receive a carboplatin-based regimen instead. We
      aimed to identify factors associated with use of a cisplatin-based regimen and
      explore its association with other quality-of-care measures. METHODS: This
      analysis was part of the Florida Initiative for Quality Cancer Care, an audit and
      feedback project among 11 medical oncology practices. Feedback-sharing sessions
      based on findings of year 2006 took place in 2008. Eligible patients were random
      samples of those with resected stage I to III non-small-cell lung cancer treated
      in 2006 and 2009. RESULTS: In both years combined, 81 patients received adjuvant
      platinum-based doublets: 33 patients (41%) received cisplatin, and 48 patients
      (59%) received carboplatin. Use of a cisplatin-based doublet significantly
      increased in 2009 compared with 2006, from 24% to 56% (P = .006). Multivariable
      analysis determined that academic practices used cisplatin more frequently than
      nonacademic practices (odds ratios, 3.26; 95% CI, 1.19 to 8.91; P = .02).
      Moreover, patients treated in 2009 were more likely to receive cisplatin than
      those treated in 2006 (odds ratio, 4.89; 95% CI, 1.75 to 13.67; P = .002). No
      significant association between use of cisplatin and other quality-of-care
      measures was found. CONCLUSION: In this study, academic practice status and
      treatment year predicted use of adjuvant cisplatin-based chemotherapy. The
      increase in use of cisplatin in 2009, as compared with 2006, suggests that audit
      and feedback may be effective ways to promote such use.

PMID- 25991640
TI  - Editor's note.

PMID- 25991641
TI  - Corrigendum.
AB  - Kraft MD. Phosphorus and calcium: a review for the adult nutrition support
      clinician. Nutr Clin Pract. 2015;30:21-33. (Original DOI:
      10.1177/0884533614565251) In this article in the February 2015 issue of Nutrition
      in Clinical Practice, the mEq content of calcium gluconate was inaccurately
      stated as "4.56 mEq elemental Ca." It should have been written as "4.65 mEq
      elemental Ca" in the note for Table 5 on page 29, in the fourth and fifth
      paragraphs of page 29, and in Table 6 on page 30. 

PMID- 25991642
TI  - Spinal Fusion for Scoliosis in Rett Syndrome With an Emphasis on Respiratory
      Failure and Opioid Usage.
AB  - Our objective was to characterize our experience with 8 patients with Rett
      syndrome undergoing scoliosis surgery in regard to rates of respiratory failure
      and rates of ventilator-acquired pneumonia in comparison to patients with
      neurologic scoliosis and adolescent idiopathic scoliosis. This study was a
      retrospective chart review of patients undergoing scoliosis surgery at a tertiary
      children's hospital. Patients were divided into 3 groups: (1) adolescent
      idiopathic scoliosis, (2) neurologic scoliosis, and (3) Rett syndrome. There were
      133 patients with adolescent idiopathic scoliosis, 48 patients with neurologic
      scoliosis, and 8 patients with Rett syndrome. We found that patients with Rett
      syndrome undergoing scoliosis surgery have higher rates of respiratory failure
      and longer ventilation times in the postoperative period when compared with both
      adolescent idiopathic scoliosis and neurologic scoliosis patients. There is
      insufficient evidence to suggest a difference in the incidence of ventilator
      acquired pneumonia between the Rett syndrome and the neurologic scoliosis group.
      We believe our findings are the first in the literature to show a statistically
      significant difference between these 3 groups in regard to incidence of
      respiratory failure. 

PMID- 25991643
TI  - Authors of report on cost of visitors and migrants to the NHS reply to letter
      calling for end to political rhetoric on health tourism.

PMID- 25991644
TI  - Persistence of the rotavirus A genome in mesenteric lymph nodes of cattle raised
      on farms.
AB  - Previous studies revealed that rotavirus A (RVA) is present in not only the small
      intestine but also various organs. It was reported that RVA persisted in
      mesenteric lymph nodes (MLNs) in experimental models. However, there have been no
      reports focused on RVA in MLNs of animals under natural conditions. In this
      study, in order to investigate the persistence of the RVA genome in MLNs in
      cattle under natural conditions, reverse transcription-semi-nested PCR was
      carried out to detect RVA genomes in the MLNs from 17 calves that had been
      subjected to autopsy examinations. RVA genomes were detected in MLNs from 10 (~60
      %) of the 17 autopsied calves. MLNs from 170 healthy adult cattle that had been
      slaughtered were also examined; 15 (~10  %) of the 170 cattle had RVA genomes in
      their MLNs, indicating that RNA genomes are found frequently in MLNs of cattle
      under natural conditions. Genetic analyses revealed that RVAs in MLNs were
      classified as G and/or P genotypes generally prevalent in bovines. Basically, the
      strains in intestinal contents were genetically identical to those in MLNs from
      individual cattle, suggesting that bovine RVAs have the ability to spread from
      the intestine to MLNs. Furthermore, amongst RVA-positive cattle, six of 10
      autopsied calves and 12 of 15 healthy adult cattle were negative for the virus in
      the intestinal contents, indicating that bovine RVA genomes can persist in MLNs
      after viral clearance in the digestive tract. 

PMID- 25991645
TI  - Good Sleep Health in Urban Children With Asthma: A Risk and Resilience Approach.
AB  - OBJECTIVES: To identify children demonstrating "good" sleep health in a sample of
      urban children with persistent asthma; to compare sociocontextual, asthma
      clinical characteristics, and sleep behaviors in children with "good" versus
      "poor" sleep health; and to examine protective effects of family-based health
      behaviors on sleep health. METHODS: Participants were 249 Black (33%), Latino
      (51%) and non-Latino White (16%) children with asthma, ages 7-9 years, and their
      primary caregivers.  RESULTS: 32 percent of children had "good" sleep health.
      Well-controlled asthma and better lung function were more likely in this group.
      In the context of urban risks, sleep hygiene appeared to be a protective factor
      associated with better sleep quality. The protective effect of asthma management
      functioned differently by ethnic group. CONCLUSIONS: This study identifies
      protective processes that may guard against urban risks to optimize sleep health
      in children with asthma. Intervention programs can be tailored to consider
      specific supports that enhance sleep health in this high-risk group.

PMID- 25991646
TI  - Family Functioning, Eosinophil Activity, and Symptoms in Children With Asthma.
AB  - OBJECTIVE: We examined prospective connections among parental depressive
      symptoms, family dysfunction, and eosinophil activity in children with asthma.
      METHODS: 81 children with asthma and their parents completed two laboratory
      visits across a 1-year period. At baseline and 1 year later, parents reported
      about their depressive symptoms and family dysfunction. We collected peripheral
      blood in children to measure eosinophil counts and eosinophil cationic protein.
      Following visits, children recorded their asthma symptoms for 2 weeks. RESULTS:
      After controlling for demographic and biomedical covariates, a significant T1 *
      T2 Family Dysfunction interaction emerged, suggesting that the links between
      family dysfunction at T1 and eosinophil counts and activity at T2 depended on
      family functioning at T2. Parental depressive symptoms were unrelated to
      eosinophil activity and asthma symptoms. CONCLUSIONS: These findings suggest that
      improvements in family functioning are associated with decreases in eosinophil
      activity, which may contribute to inflammatory processes that affect airway
      function.

PMID- 25991647
TI  - Mass spectrometry-based microassay of (2)H and (13)C plasma glucose labeling to
      quantify liver metabolic fluxes in vivo.
AB  - Mouse models designed to examine hepatic metabolism are critical to diabetes and
      obesity research. Thus, a microscale method to quantitatively assess hepatic
      glucose and intermediary metabolism in conscious, unrestrained mice was
      developed. [(13)C3]propionate, [(2)H2]water, and [6,6-(2)H2]glucose isotopes were
      delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J
      mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on
      three 40-MUl arterial plasma glucose samples obtained during the euglycemic
      isotopic steady state. Model-based regression of hepatic glucose and citric acid
      cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model
      to track carbon and hydrogen atom transitions through the network and thereby
      simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from
      glycogen diminished, and endogenous glucose production was exclusively
      gluconeogenic with prolonged fasting. Gluconeogenic flux from phosphoenolpyruvate
      (PEP) remained stable, whereas that from glycerol modestly increased from short-
      to long-term fasting. CAC flux [i.e., citrate synthase (VCS)] was reduced with
      long-term fasting. Interestingly, anaplerosis and cataplerosis increased with
      fast duration; accordingly, pyruvate carboxylation and the conversion of
      oxaloacetate to PEP were severalfold higher than VCS in long-term fasted mice.
      This method utilizes state-of-the-art in vivo methodology and comprehensive
      isotopomer modeling to quantify hepatic glucose and intermediary fluxes during
      physiological stress in mice. The small plasma requirements permit serial
      sampling without stress and the affirmation of steady-state glucose kinetics.
      Furthermore, the approach can accommodate a broad range of modeling assumptions,
      isotope tracers, and measurement inputs without the need to introduce ad hoc
      mathematical approximations. 

PMID- 25991648
TI  - theta-Defensin RTD-1 improves insulin action and normalizes plasma glucose and
      FFA levels in diet-induced obese rats.
AB  - Inflammation is implicated in metabolic abnormalities in obesity and type 2
      diabetes. Because theta-defensins have anti-inflammatory activities, we tested
      whether RTD-1, a theta-defensin, improves metabolic conditions in diet-induced
      obesity (DIO). DIO was induced by high-fat feeding in obese-prone CD rats from 4
      wk of age. Starting at age 10 wk, the DIO rats were treated with saline or RTD-1
      for 4 or 8 wk. DIO rats gained more weight than low-fat-fed controls. RTD-1
      treatment did not alter body weight or calorie intake in DIO rats. Plasma
      glucose, FFA, triglyceride (TG), and insulin levels increased in DIO rats; RTD-1
      normalized plasma glucose and FFA levels and showed tendencies to lower plasma
      insulin and TG levels. Hepatic and skeletal muscle TG contents increased in DIO
      rats; RTD-1 decreased muscle, but not hepatic, TG content. Insulin sensitivity,
      estimated using homeostasis model assessment of insulin resistance and the
      glucose clamp technique, decreased in DIO rats, but this change was markedly
      reversed by RTD-1. RTD-1 had no significant effects on plasma cytokine/chemokine
      levels or IL-1beta and TNF-alpha expression in liver or adipose tissues. RTD-1
      treatment decreased hepatic expression of phosphoenolpyruvate carboxykinase and
      glucose-6-phosphatase, suggesting that the effect of RTD-1 on plasma glucose (or
      insulin action) might be mediated by its effect to decrease hepatic
      gluconeogenesis. Thus, RTD-1 ameliorated insulin resistance and normalized plasma
      glucose and FFA levels in DIO rats, supporting the potential of RTD-1 as a novel
      therapeutic agent for insulin resistance, metabolic syndrome, or type 2 diabetes.

PMID- 25991650
TI  - Promises and Pitfalls in the Use of "Big Data" for Clinical Research.

PMID- 25991649
TI  - Hepatic insulin sensitivity in healthy and prediabetic subjects: from a dual- to
      a single-tracer oral minimal model.
AB  - Recently, a model was proposed to assess hepatic insulin sensitivity during a
      meal, i.e., the ability of insulin to suppress glucose production (EGP), SI (P).
      The model was developed on EGP data obtained from a triple-tracer meal and the
      tracer-to-tracee clamp technique and validated against the euglycemic
      hyperinsulinemic clamp. The aim of this study was to assess whether SI (P) can be
      obtained from plasma concentrations measured after a single-tracer meal by
      incorporating the above EGP model into the oral glucose minimal model by
      describing both glucose production and disposal (OMM(PD)). Triple-tracer meal
      data of two databases (20 healthy and 60 healthy and prediabetic subjects) were
      used. Virtually model-independent EGP estimates were calculated. OMM(PD) was
      identified on exogenous and endogenous glucose concentrations, providing indices
      of SI (P), disposal insulin sensitivity (SI (D)), and EGP. The model fitted the
      data well, and SI (P) and SI (D) were estimated with precision in both databases
      (SI (P) = 5.48 +/- 0.54 10(-4) dl.kg(-1).min(-1) per MUU/ml and SI (D) = 9.93 +/-
      2.18 10(-4) dl.kg(-1).min(-1) per MUU/ml in healthy; SI (P) = 5.41 +/- 3.55 10(
      4) dl.kg(-1).min(-1) per MUU/ml and SI (D) = 5.34 +/- 6.17 10(-4) dl.kg(-1).min(
      1) per MUU/ml, in healthy and prediabetic subjects). Estimated SI (P) and that
      derived from the triple-tracer EGP model were very similar on average. Moreover,
      the time course of EGP normalized to basal EGP (EGPb), and EGP/EGPb agreed with
      the results obtained using the triple-tracer method. In this study, we have
      demonstrated that SI (P), SI (D), and EGP/EGPb time course can be estimated
      reliably from a single-tracer meal protocol in both healthy and prediabetic
      subjects. 

PMID- 25991651
TI  - Missing Teeth Predict Incident Cardiovascular Events, Diabetes, and Death.
AB  - Periodontitis, the main cause of tooth loss in the middle-aged and elderly,
      associates with the risk of atherosclerotic vascular disease. The objective was
      to study the capability of the number of missing teeth in predicting incident
      cardiovascular diseases (CVDs), diabetes, and all-cause death. The National
      FINRISK 1997 Study is a Finnish population-based survey of 8,446 subjects with 13
      y of follow-up. Dental status was recorded at baseline in a clinical examination
      by a trained nurse, and information on incident CVD events, diabetes, and death
      was obtained via national registers. The registered CVD events included coronary
      heart disease events, acute myocardial infarction, and stroke. In Cox regression
      analyses, having >=5 teeth missing was associated with 60% to 140% increased
      hazard for incident coronary heart disease events (P < 0.020) and acute
      myocardial infarction (P < 0.010). Incident CVD (P < 0.043), diabetes (P <
      0.040), and death of any cause (P < 0.019) were associated with >=9 missing
      teeth. No association with stroke was observed. Adding information on missing
      teeth to established risk factors improved risk discrimination of death (P =
      0.0128) and provided a statistically significant net reclassification improvement
      for all studied end points. Even a few missing teeth may indicate an increased
      risk of CVD, diabetes, or all-cause mortality. When individual risk factors for
      chronic diseases are assessed, the number of missing teeth could be a useful
      additional indicator for general medical practitioners. 

PMID- 25991652
TI  - Use of Benzodiazepines in Alzheimer's Disease: A Systematic Review of Literature.
AB  - BACKGROUND: Benzodiazepines are frequently prescribed in patients with
      Alzheimer's disease. Unfortunately, studies evaluating their benefits and risks
      in these patients are limited. METHODS: Clinical trials focusing on the effect of
      benzodiazepines on cognitive functions, disease progression, behavioral symptoms,
      sleep disturbances, and the general frequency of benzodiazepine use were included
      in this review. Published articles from January 1983 to January 2015 were
      identified using specific search terms in MEDLINE and PubMed Library according to
      the recommendations of The Strengthening the Reporting of Observational Studies
      in Epidemiology initiative. RESULTS: Of the 657 articles found, 18 articles met
      predefined selection criteria and were included in this review (8 on frequency, 5
      on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of
      benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated
      cognitive deterioration in association with benzodiazepine use. Two studies
      reported clinical efficacy for lorazepam and alprazolam to reduce agitation in
      Alzheimer's disease patients. No evidence was found for an improvement of sleep
      quality using benzodiazepines. CONCLUSION: This systematic review shows a
      relatively high prevalence of benzodiazepine use but limited evidence for
      clinical efficacy in Alzheimer's disease patients. However, there is a paucity of
      methodologically high quality controlled clinical trials. Our results underscore
      a need for randomized controlled trials in this area.

PMID- 25991653
TI  - Involvement of Glutamate NMDA Receptors in the Acute, Long-Term, and Conditioned
      Effects of Amphetamine on Rat 50 kHz Ultrasonic Vocalizations.
AB  - BACKGROUND: Rats emit 50 kHz ultrasonic vocalizations (USVs) in response to
      either natural or pharmacological pleasurable stimuli, and these USVs have
      emerged as a new behavioral measure for investigating the motivational properties
      of drugs. Earlier studies have indicated that activation of the dopaminergic
      system is critically involved in 50 kHz USV emissions. However, evidence also
      exists that non-dopaminergic neurotransmitters participate in this behavioral
      response. METHODS: To ascertain whether glutamate transmission plays a role in 50
      kHz USV emissions stimulated by amphetamine, rats received five amphetamine (1
      2mg/kg, i.p.) administrations on alternate days in a test cage, either alone or
      combined with the glutamate N-methyl-D-aspartate receptor antagonist MK-801 (0.1
      0.5mg/kg, i.p.). Seven days after treatment discontinuation, rats were re-exposed
      to the test cage to assess drug conditioning, and afterwards received a drug
      challenge. USVs and locomotor activity were evaluated, along with
      immunofluorescence for Zif-268 in various brain regions and spontaneous
      alternation in a Y maze. RESULTS: Amphetamine-treated rats displayed higher 50
      kHz USV emissions and locomotor activity than vehicle-treated rats, and emitted
      conditioned vocalizations on test cage re-exposure. Rats co-administered
      amphetamine and MK-801 displayed lower and dose-dependent 50 kHz USV emissions,
      but not lower locomotor activity, during repeated treatment and challenge, and
      scarce conditioned vocalization compared with amphetamine-treated rats. These
      effects were associated with lower levels of Zif-268 after amphetamine challenge
      and spontaneous alternation deficits. CONCLUSIONS: These results indicate that
      glutamate transmission participates in the acute, long-term, and conditioned
      effects of amphetamine on 50 kHz USVs, possibly by influencing amphetamine
      induced long-term neuronal changes and/or amphetamine-associated memories.

PMID- 25991654
TI  - Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia.
AB  - BACKGROUND: Despite adequate treatment with antipsychotics, a substantial number
      of patients with schizophrenia demonstrate only suboptimal clinical outcome. To
      overcome this challenge, various psychopharmacological combination strategies
      have been used, including antidepressants added to antipsychotics. METHODS: To
      analyze the efficacy of add-on antidepressants for the treatment of negative,
      positive, cognitive, depressive, and antipsychotic-induced extrapyramidal
      symptoms in schizophrenia, published randomized controlled trials assessing the
      efficacy of adjunctive antidepressants in schizophrenia were reviewed using the
      following parameters: baseline clinical characteristics and number of patients,
      their on-going antipsychotic treatment, dosage of the add-on antidepressants,
      duration of the trial, efficacy measures, and outcomes. RESULTS: There were 36
      randomized controlled trials reported in 41 journal publications (n=1582). The
      antidepressants used were the selective serotonin reuptake inhibitors,
      duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone,
      and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for
      negative symptoms and both seemed to enhance neurocognition. Trazodone and
      nefazodone appeared to improve the antipsychotics-induced extrapyramidal
      symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No
      clear evidence supporting selective serotonin reuptake inhibitors' efficacy on
      any clinical domain of schizophrenia was found. Add-on antidepressants did not
      worsen psychosis. CONCLUSIONS: Despite a substantial number of randomized
      controlled trials, the overall efficacy of add-on antidepressants in
      schizophrenia remains uncertain mainly due to methodological issues. Some
      differences in efficacy on several schizophrenia domains seem, however, to exist
      and to vary by the antidepressant subgroups--plausibly due to differences in the
      mechanisms of action. Antidepressants may not worsen the course of psychosis.
      Better designed, larger, and longer randomized controlled trials are needed.

PMID- 25991655
TI  - A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity.
AB  - BACKGROUND: Modulating the methylation process induces broad biochemical changes,
      some of which may be involved in schizophrenia. Methylation is in particular
      central to epigenesis, which is also recognized as a factor in the etiology of
      schizophrenia. Because methionine administration to patients with schizophrenia
      has been reported to exacerbate their psychotic symptoms and because mice treated
      with methionine exhibited social deficits and prepulse inhibition impairment, we
      investigated whether methionine administration could lead to behavioral changes
      that reflect schizophrenic symptoms in mice. METHODS: l-Methionine was
      administered to mice twice a day for 7 days. RESULTS: We found that this
      treatment induces behavioral responses that reflect the 3 types of schizophrenia
      like symptoms (positive, negative, or cognitive deficits) as monitored in a
      battery of behavioral assays (locomotion, stereotypy, social interaction, forced
      swimming, prepulse inhibition, novel object recognition, and inhibitory
      avoidance). Moreover, these responses were differentially reversed by typical
      haloperidol and atypical clozapine antipsychotics in ways that parallel their
      effects in schizophrenics. CONCLUSION: We thus propose the l-methionine treatment
      as an animal model recapitulating several symptoms of schizophrenia. We have
      established the face and predictive validity for this model. Our model relies on
      an essential natural amino acid and on an intervention that is relatively simple
      and time effective and may offer an additional tool for assessing novel
      antipsychotics.

PMID- 25991656
TI  - The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research
      and Clinical Implications.
AB  - The neurotransmitters serotonin and dopamine both have a critical role in the
      underlying neurobiology of different behaviors. With focus on the interplay
      between dopamine and serotonin, it has been proposed that dopamine biases
      behavior towards habitual responding, and with serotonin offsetting this
      phenomenon and directing the balance toward more flexible, goal-directed
      responding. The present focus paper stands in close relationship to the
      publication by Worbe et al. (2015), which deals with the effects of acute
      tryptophan depletion, a neurodietary physiological method to decrease central
      nervous serotonin synthesis in humans for a short period of time, on the balance
      between hypothetical goal-directed and habitual systems. In that research, acute
      tryptophan depletion challenge administration and a following short-term
      reduction in central nervous serotonin synthesis were associated with a shift of
      behavioral performance towards habitual responding, providing further evidence
      that central nervous serotonin function modulates the balance between goal
      directed and stimulus-response habitual systems of behavioral control. In the
      present focus paper, we discuss the findings by Worbe and colleagues in light of
      animal experiments as well as clinical implications and discuss potential future
      avenues for related research. 

PMID- 25991657
TI  - What healthcare teams find ethically difficult.
AB  - BACKGROUND: Ethically difficult situations are frequently encountered by
      healthcare professionals. Moral case deliberation is one form of clinical ethics
      support, which has the goal to support staff to manage ethical difficulties.
      However, little is known which difficult situations healthcare teams need to
      discuss. AIM: To explore which kinds of ethically difficult situations
      interprofessional healthcare teams raise during moral case deliberation. RESEARCH
      DESIGN: A series of 70 moral case deliberation sessions were audio-recorded in 10
      Swedish workplaces. A descriptive, qualitative approach was applied, using
      thematic content analysis. Ethical considerations: An advisory statement
      specifying no objections to the study was provided from an Ethical Review Board,
      and consent to be recorded was assumed by virtue of participation in the moral
      case deliberation. FINDINGS: Three themes emerged: powerlessness over managing
      difficult interactions with patients and next-of-kin, unease over unsafe and
      unequal care, and uncertainty over who should have power over care decisions. The
      powerlessness comprised feelings of insufficiency, difficulties to respond or
      manage patient's/next-of-kin's emotional needs or emotional outbursts and
      discouragement over motivating patients not taking responsibility for themselves.
      They could be uncertain over the patient's autonomy, who should have power over
      life and death, disclosing the truth or how much power next-of-kin should have.
      DISCUSSION: The findings suggest that the nature of the ethically difficult
      situations brought to moral case deliberations contained more relational-oriented
      ethics than principle-based ethics, were permeated by emotions and the
      uncertainties were pervaded by power aspects between stakeholders. CONCLUSION:
      MCD can be useful in understanding the connection between ethical issues and
      emotions from a team perspective.

PMID- 25991658
TI  - Enhancing students' moral competence in practice: Challenges experienced by
      Malawian nurse teachers.
AB  - BACKGROUND: Nurses and student nurses in Malawi often encounter challenges in
      taking a moral course of action. Several studies have demonstrated a need for
      increased awareness of ethical issues in the nursing education. OBJECTIVE: To
      explore the challenges experienced by nurse teachers in Malawi in their efforts
      to enhance students' moral competence in clinical practice. RESEARCH DESIGN: A
      qualitative hermeneutic approach was employed to interpret the teachers'
      experiences. PARTICIPANTS AND RESEARCH CONTEXT: Individual interviews (N = 8) and
      a focus group interview with teachers (N = 9) from different nursing colleges
      were conducted. ETHICAL CONSIDERATIONS: Ethical approval was granted and all
      participants signed their informed consent. FINDINGS: Two overall themes emerged:
      (1) authoritarian learning climate, with three subthemes: (a) fear of making
      critical comments about clinical practice, (b) fear of disclosing mistakes and
      lack of knowledge and (c) lack of a culture of critical discussion and reflection
      that promotes moral competence; and (2) discrepancy between expectations on
      learning outcome from nursing college and the learning opportunities in practice
      comprising three subthemes: (a) gap between the theory taught in class and
      learning opportunities in clinical practice, (b) lack of good role models and (c)
      lack of resources. DISCUSSION: Our findings indicated that showing respect was a
      central objective when the students were assessed in practice. A number of
      previous studies have enlightened the need for critical reflection in nursing
      education. Few studies have linked this to challenges experienced by teachers for
      development of moral competence in practice. This is one of the first such
      studies done in an African setting. CONCLUSION: There is a clear relationship
      between the two themes. A less authoritarian learning climate may enhance
      critical reflection and discussion between students, teachers and nurses. This
      can narrow the gap between the theory taught in college and what is demonstrated
      in clinical practice. Moral competence must be enhanced in order to ensure
      patients' rights and safety.

PMID- 25991660
TI  - Re: "joint association of genome-wide association study-identified susceptibility
      loci and dietary patterns in risk of renal cell carcinoma among non-Hispanic
      Whites".

PMID- 25991659
TI  - Nurses' knowledge and attitudes toward aged sexuality in Flemish nursing homes.
AB  - BACKGROUND: Admission to a nursing home does not necessarily diminish an older
      person's desire for sexual expression and fulfillment. Given that nursing staff
      directly and indirectly influence the range of acceptable sexual expressions of
      nursing home residents, their knowledge and attitudes toward aged sexuality can
      have far-reaching effects on both the quality of care they provide to residents
      and the self-image and well-being of these residents. RESEARCH OBJECTIVES: To
      investigate nursing staff's knowledge and attitudes toward aged sexuality, to
      determine whether certain sociodemographic factors of the nursing staff relate to
      their knowledge and attitudes toward later-life sexuality, and to examine the
      relationship between knowledge and attitudes. RESEARCH DESIGN: Descriptive cross
      sectional survey study. RESEARCH PARTICIPANTS AND RESEARCH CONTEXT: The
      administered questionnaire collected sociodemographic data and data from an
      adapted, Dutch version of the Aging Sexual Knowledge and Attitudes Scale. Data
      were collected from November 2011 through April 2012. A total of 43
      geographically dispersed nursing homes in Flanders, Belgium, participated. Out of
      a potential research sample of 2228 nursing staff respondents, 1166 participated.
      ETHICAL CONSIDERATIONS: The study protocol was approved by the Ethics Committee
      of the Faculty of Medicine of the KU Leuven. FINDINGS: Nursing staff appeared to
      be moderately knowledgeable about aged sexuality and displayed a rather positive
      attitude toward sexuality in older people. Significant relationships between
      various variables were found both at univariable and multivariable levels.
      Knowledge and attitudes proved to be positively related, indicating that a higher
      level of knowledge of aged sexuality is associated with a more positive attitude
      toward sexuality in later life. DISCUSSION: Research findings are discussed
      within a broader international context. CONCLUSION: There is room for improvement
      for both nursing staff's knowledge and attitudes toward aged sexuality. This
      might be aided by appropriate educational interventions. Our results identified
      different target groups of nursing home staff for these interventions.

PMID- 25991661
TI  - Thermoactinomyces guangxiensis sp. nov., a thermophilic actinomycete isolated
      from mushroom compost.
AB  - A novel thermophilic actinomycete, designated strain CD-1(T), was isolated from
      mushroom compost in Nanning, Guangxi province, China. The strain grew at 37-55 
      degrees C (optimum 45-50  degrees C), pH 6.0-11.0 (optimum pH 7.0-9.0) and with 0
      2.0% NaCl (optimum 0-1.0%), formed well-developed white aerial mycelium and pale
      yellow vegetative mycelium, and single endospores (0.8-1.0 MUm diameter) were
      borne on long sporophores (2-3 MUm length). The endospores were spherical
      polyhedron in shape with smooth surface. Based on its phenotypic and phylogenetic
      characteristics, strain CD-1(T) is affiliated to the genus Thermoactinomyces. It
      contained meso-diaminopimelic acid as the diagnostic diamino acid; the whole-cell
      sugars were ribose and glucose. Major fatty acids were iso-C15 :  0, C16 : 0,
      anteiso-C15  : 0 and iso-C17  : 0. MK-7 was the predominant menaquinone. The
      polar phospholipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylethanolamine containing hydroxylated fatty
      acids, ninhydrin-positive glycophospholipid, an unknown phospholipid and
      glycolipids. The G+C content of the genomic DNA was 48.8%. 16S rRNA gene sequence
      analysis showed that the organism was closely related to Lihuaxuella thermophila
      YIM 77831(T) (95.69% sequence similarity), Thermoactinomyces daqus H-18(T)
      (95.49%), Laceyella putida KCTC 3666(T) (95.05%), Thermoactinomyces vulgaris KCTC
      9076(T) (95.01%) and Thermoactinomyces intermedius JCM 3312(T) (94.55%). Levels
      of DNA-DNA relatedness between strain CD-1T and Lihuaxuella thermophila JCM
      18059(T), Thermoactinomyces daqus DSM 45914(T), Laceyella putida JCM 8091(T),
      Thermoactinomyces vulgaris JCM 3162(T) and Thermoactinomyces intermedius JCM
      3312(T) were low (22.8, 33.3, 24.7, 29.4 and 30.0%, respectively). A battery of
      phenotypic, genotypic and DNA-DNA relatedness data indicated that strain CD-1T
      represented a novel species of the genus Thermoactinomyces, for which the name
      Thermoactinomyces guangxiensis sp. nov. is proposed. The type strain is CD-1(T) (
      = ATCC BAA-2630(T) = CGMCC 4.7156(T)).

PMID- 25991662
TI  - Prolixibacter denitrificans sp. nov., an iron-corroding, facultatively aerobic,
      nitrate-reducing bacterium isolated from crude oil, and emended descriptions of
      the genus Prolixibacter and Prolixibacter bellariivorans.
AB  - The facultatively aerobic, non-hydrogenotrophic, iron (Fe0)-corroding, nitrate
      reducing Prolixibacter sp. strain MIC1-1(T) was characterized for representation
      of a novel species of the genus Prolixibacter. Strain MIC1-1(T) grew optimally at
      35-37  degrees C, at pH 6.5 and with 2% (w/v) NaCl. Strain MIC1-1(T) also grew
      fermentatively on some pentoses, hexoses, disaccharides and soluble starch.
      Succinic acid was the major end-product from D-glucose fermentation. Strain MIC1
      1(T) was differentiated from the type strain of Prolixibacter bellariivorans by
      cell size, optimum growth temperature, range of temperature and NaCl for growth,
      and nitrate reduction. On the basis of phenotypic features and the phylogenetic
      position, a novel species of the genus Prolixibacter is proposed for strain MIC1
      1(T), to be named Prolixibacter denitrificans sp. nov. The type strain is MIC1
      1(T) ( = JCM 18694(T) = NBRC 102688(T)= DSM 27267(T)). Emended descriptions of
      the genus Prolixibacter and Prolixibacter bellariivorans are also provided.

PMID- 25991663
TI  - Oceanisphaera psychrotolerans sp. nov., isolated from coastal sediment samples.
AB  - A novel aerobic, Gram-staining-negative bacterium, designated strain LAM-WHM
      ZC(T), was isolated from coastal sediment samples from the Bohai Sea, near
      Yantai, China. Cells of LAM-WHM-ZC(T) were non-motile, short-rod- or coccoid
      shaped. The temperature and pH ranges for growth were 4-40  degrees C (optimum:
      20-33  degrees C) and pH 5-9 (optimum: pH 7.5). The strain did not require NaCl
      for growth but tolerated up to 10% NaCl (w/v). The major fatty acids of strain
      LAM-WHM-ZC(T) were summed feature 3, C12 : 0, C16 : 0, summed feature 2 and
      summed feature 8. The predominant respiratory quinone was ubiquinone Q-8. The
      main polar lipids were diphosphatidyglycerol, phosphatigylethanolamine,
      phosphatidyglycerol, one phospholipid and four unidentified glycolipids. The DNA
      G+C content was 59.3 mol% as determined by the melting temperature (Tm) method.
      Analysis of the 16S rRNA gene sequence indicated that the isolate represented a
      member of the genus Oceanisphaera and was closely related to Oceanisphaera
      arctica KCTC 23013(T), Oceanisphaera litoralis DSM 15406(T), Oceanisphaera
      sediminis KACC 15117(T) and Oceanisphaera donghaensis KCTC 12522(T) with 97.7%,
      97.1%, 96.6% and 96.6% sequence similarity, respectively. The DNA-DNA
      hybridization values between strain LAM-WHM-ZC(T) and the four reference strains
      were 47.4 +/- 2.8%, 33.5 +/- 2.2%, 28.4 +/- 1.8% and 13.7 +/- 0.8%, respectively.
      Based on its phenotypic and genotypic properties, strain LAM-WHM-ZC(T) is
      suggested to represent a novel species of the genus Oceanisphaera, for which the
      name Oceanisphaera psychrotolerans sp. nov. is proposed. The type strain is LAM
      WHM-ZC(T) ( = ACCC 06516(T) = JCM 30466(T)).

PMID- 25991664
TI  - Polypharmacology of small molecules targeting the ubiquitin-proteasome and
      ubiquitin-like systems.
AB  - Targeting the ubiquitin-proteasome system (UPS) and ubiquitin-like signalling
      systems (UBL) has been considered a promising therapeutic strategy to treat
      cancer, neurodegenerative and immunological disorders. There have been multiple
      efforts recently to identify novel compounds that efficiently modulate the
      activities of different disease-specific components of the UPS-UBL. However, it
      is evident that polypharmacology (the ability to affect multiple independent
      protein targets) is a basic property of small molecules and even highly potent
      molecules would have a number of "off target" effects. Here we have explored
      publicly available high-throughput screening data covering a wide spectrum of
      currently accepted drug targets in order to understand polypharmacology of small
      molecules targeting different components of the UPS-UBL. We have demonstrated
      that molecules targeting a given UPS-UBL protein also have high odds to target a
      given off target spectrum. Moreover, the off target spectrum differs
      significantly between different components of UPS-UBL. This information can be
      utilized further in drug discovery efforts, to improve drug efficiency and to
      reduce the risk of potential side effects of the prospective drugs designed to
      target specific UPS-UBL components. 

PMID- 25991665
TI  - Nuclear localization of epidermal growth factor receptor (EGFR) in
      ameloblastomas.
AB  - BACKGROUND: Ameloblastoma is a locally invasive neoplasm often associated with
      morbidity and facial deformities, showing increased Epidermal Growth Factor
      Receptor (EGFR) expression. Inhibition of EGFR was suggested as a treatment
      option for a subset of ameloblastomas. However, there are resistance mechanisms
      that impair anti-EGFR therapies. One important resistance mechanism for EGFR
      inhibition is the EGFR nuclear localization, which activates genes responsible
      for its mitogenic effects, such as Cyclin D1. METHODS: We assessed EGFR nuclear
      localization in encapsulated (unicystic, n = 3) and infiltrative (multicystic, n
      = 11) ameloblastomas and its colocalization with Cyclin D1 by using anti-EGFR and
      anti-lamin B1 double labeling immunofluorescence analyzed by confocal microscopy.
      Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples
      were used for comparison. RESULTS: Twelve cases of ameloblastoma exhibited
      nuclear EGFR colocalization with lamin B1. This positive staining was mainly
      observed in the ameloblast-like cells. The EGFR nuclear localization was also
      observed in control samples. In addition, nuclear EGFR colocalized with Cyclin D1
      in ameloblastomas. CONCLUSIONS: Nuclear EGFR occurs in ameloblastomas in
      association with Cyclin D1 expression, which is important in terms of tumor
      biology clarification and raises a concern about anti-EGFR treatment resistance
      in ameloblastomas.

PMID- 25991667
TI  - Rapatar, a nanoformulation of rapamycin, decreases chemically-induced benign
      prostate hyperplasia in rats.
AB  - Benign prostatic hyperplasia (BPH) is the most common age-related disease in men.
      Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin,
      in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia
      in ventral lobes and lateral/dorsal lobes, respectively. We found that Rapatar
      prevented hypertrophic and hyperplastic abnormalities and degenerative
      alterations in both BPH models. Rapatar normalized weight of the lateral lobes in
      sulpiride-induced BPH, the most relevant animal model of human BPH. Unlike
      Finasteride, a standard therapy of BPH, Rapatar reduced inflammation caused by
      sulpiride. No obvious side effects of Rapatar were detected. Our data provide a
      rationale for clinical trials of Rapatar in patients suffering from BPH. 

PMID- 25991668
TI  - Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by
      inducing DR5 and causing caspase-mediated HDAC3 cleavage.
AB  - TRAIL can induce apoptosis in some cancer cells and is an immune effector in the
      surveillance and elimination of developing tumors. Yes, some cancers are
      resistant to TRAIL. Delphinidin, a polyphenolic compound contained in brightly
      colored fruits and vegetables, has anti-inflammatory, anti-oxidant, and anti
      tumorigenic activities. Here we showed that delphinidin sensitized TRAIL
      resistant human prostate cancer cells to undergo apoptosis. Cells treated with
      delphinidin and TRAIL activated the extrinsic and intrinsic pathways of caspase
      activation. TRAIL-induced apoptosis in prostate cancer cells pretreated with
      delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of
      histone deacetylase 3 (HDAC3). In conclusion, delphinidin sensitizes prostate
      cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase
      mediated HDAC3 cleavage. Our data reveal a potential way of chemoprevention of
      prostate cancer by enabling TRAIL-mediated apoptosis. 

PMID- 25991666
TI  - EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone
      deacetylase in primary neuron cells.
AB  - Prion diseases caused by aggregated misfolded prion protein (PrP) are
      transmissible neurodegenerative disorders that occur in both humans and animals.
      Epigallocatechin-3-gallate (EGCG) has preventive effects on prion disease;
      however, the mechanisms related to preventing prion diseases are unclear. We
      investigated whether EGCG, the main polyphenol in green tea, prevents neuron cell
      damage induced by the human prion protein. We also studied the neuroprotective
      mechanisms and proper signals mediated by EGCG. The results showed that EGCG
      protects the neuronal cells against human prion protein-induced damage through
      inhibiting Bax and cytochrome c translocation and autophagic pathways by
      increasing LC3-II and reducing and blocking p62 by using ATG5 small interfering
      (si) RNA and autophagy inhibitors. We further demonstrated that the
      neuroprotective effects of EGCG were exhibited by a class III histone
      deacetylase; sirt1 activation and the neuroprotective effects attenuated by sirt1
      inactivation using sirt1 siRNA and sirtinol. We demonstrated that EGCG activated
      the autophagic pathways by inducing sirt1, and had protective effects against
      human prion protein-induced neuronal cell toxicity. These results suggest that
      EGCG may be a therapeutic agent for treatment of neurodegenerative disorders
      including prion diseases. 

PMID- 25991670
TI  - MicroRNA-21, T helper lineage and autoimmunity.

PMID- 25991669
TI  - The miR-193a-3p-regulated ING5 gene activates the DNA damage response pathway and
      inhibits multi-chemoresistance in bladder cancer.
AB  - As the major barrier to curative cancer chemotherapy, chemoresistance presents a
      formidable challenge to both cancer researchers and clinicians. We have
      previously shown that the bladder cancer (BCa) cell line 5637 is significantly
      more sensitive to the cytoxicity of five chemotherapeutic agents than H-bc cells.
      Using an RNA-seq-based omic analysis and validation at both the mRNA and protein
      levels, we found that the inhibitor of growth 5 (ING5) gene was upregulated in
      5637 cells compared with H-bc cells, indicating that it has an inhibitory role in
      BCa chemoresistance. siRNA-mediated inhibition of ING5 increased the
      chemoresistance and inhibited the DNA damage response pathway in 5637 cells.
      Conversely, forced expression of EGFP-ING5 decreased the chemoresistance of and
      activated the DNA damage response pathway in H-bc cells. We also showed that ING5
      gene expression is inhibited by miR-193a-3p and is instrumental in miR-193a-3p's
      role in activating BCa chemoresistance. Our results demonstrate both the role and
      mechanism of inhibition of BCa chemoresistance by ING5. 

PMID- 25991671
TI  - Forced expression of fibroblast growth factor 21 reverses the sustained
      impairment of liver regeneration in hPPARalpha(PAC) mice due to dysregulated bile
      acid synthesis.
AB  - Peroxisome proliferator activated receptor alpha (PPARalpha) stimulates
      hepatocellular proliferation is species-specific. Activation of mouse, but not
      human, PPARalpha induces hepatocellular proliferation, hepatomegaly, and liver
      cancer. Here we tested the hypothesis that human and mouse PPARalpha affects
      liver regeneration differentially. PPARalpha-humanized mice (hPPARalpha(PAC))
      were similar to wild type mice in responding to fasting-induced PPARalpha
      signaling. However, these mouse livers failed to regenerate in response to
      partial hepatectomy (PH). The liver-to-body weight ratios did not recover even 3
      months after PH in hPPARalpha(PAC). The mouse PPARalpha-mediated down-regulation
      of let-7c was absent in hPPARalpha(PAC), which might partially be responsible for
      impaired proliferation. After PH, hPPARalpha(PAC) displayed steatosis, necrosis,
      and inflammation mainly in periportal zone 1, which suggested bile-induced
      toxicity. Quantification of hepatic bile acids (BA) revealed BA overload with
      increased hydrophobic BA in hPPARalpha(PAC). Forced FGF21 expression in partial
      hepatectomized hPPARalpha(PAC) reduced hepatic steatosis, prevented focal
      necrosis, and restored liver mass. Compared to mouse PPARalpha, human PPARalpha
      has a reduced capacity to regulate metabolic pathways required for liver
      regeneration. In addition, FGF21 can compensate for the reduced ability of human
      PPARalpha in stimulating liver regeneration, which suggests the potential
      application of FGF21 in promoting hepatic growth in injured and steatotic livers
      in humans.

PMID- 25991672
TI  - Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status
      and outcome.
AB  - In this study we aimed to analyze the biological mechanisms underlying apparently
      different modes of peritoneal tumor spread in serous ovarian cancer: miliary
      (widespread, millet-like lesions) versus non-miliary (bigger, exophytically
      growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients
      were analyzed by RNA-sequencing and flow cytometry. On the basis of differential
      gene expression between miliary and non-miliary, gene signatures were developed.
      A calculated tumor spread factor revealed a significant independent negative
      impact of miliary spread on overall survival (HR 3.77; CI95 1.14-12.39; p =
      0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing
      previously published epithelial-mesenchymal transition (EMT) gene signatures, non
      miliary spread correlated significantly with a reduced epithelial status. We
      conclude that serous ovarian cancer is a heterogeneous disease with distinct
      modes of peritoneal tumor spread, differing not only in clinical appearance, but
      also in molecular characteristics and outcome. EMT, peritoneal inflammation
      status, and therapeutic options are discussed. SIGNIFICANCE: More than half of
      serous epithelial ovarian cancer patients present with a newly described type of
      intraperitoneal tumor spread, associated with differences in the inflammation
      status, activated oncogenic pathways, lack of EMT, and thus reduced overall
      survival. Both, the diminished immune reaction and the enhanced epithelial and
      malignant characteristics of the tumor cells open new avenues for therapeutic
      options and strategies, like Catumaxomab, already in clinical use.

PMID- 25991673
TI  - Endothelial Rac1 is essential for hematogenous metastasis to the lung.
AB  - A variety of vasoactive stimuli induce endothelial permeability through Rac1, a
      membrane of Rho small GTPases. Here, we determine whether tumor-secreted
      vasoactive stimulant through Rac1 inducing permeability contributes to
      hematogenous metastasis. Activation of Rac1 was assayed in human umbilical vein
      endothelial cells (HUVEC), transendothelial passages were measured by Transwell
      chambers, and hematogenously metastatic mouse model was generated by intravenous
      injection with Lewis lung carcinoma cells (LLC). LLC secreted abundant vascular
      endothelial growth factor (VEGF) in the culture media and sera of mice bearing
      LLC xenografts or metastatic LLC, and VEGF activated Rac1 through VEGF
      receptors/PI3Kbeta signaling cascade, resulting in hyperoxidative stress and
      consequent hyperpermeability in HUVEC. Moreover, in co-culture of LLC and HUVEC,
      significant increases in endothelial permeability and transendothelial migration
      of LLC were robustly attenuated by either anti-VEGF neutralizing antibody or Rac1
      knockdown in HUVEC. Finally, in metastatic mouse model, deletion of one copy of
      Rac1 in endothelium not only significantly attenuated LLC-induced vascular
      permeability, but robustly reduced the metastasis of LLC to lungs. This study
      supports that tumor-secreted vasoactive stimuli activate Rac1 to induce
      permeability and consequent transendothelial migration of tumor cells, and that
      loss of Rac1 function in endothelium is an effective therapeutic intervention for
      hematogenous metastasis.

PMID- 25991674
TI  - Molecular-genetic and clinical characteristics of gliomas with astrocytic
      appearance and total 1p19q loss in a single institutional consecutive cohort.
AB  - The prognostic significance of 1p19q loss in astrocytic gliomas has been
      inconclusive.We collected 57 gliomas with total 1p19q loss from among 218 cases
      of WHO grade-II/III gliomas operated at Keio University Hospital between 1990 and
      2010. These tumors were classified as oligodendroglial or "astrocytic" by a WHO
      criteria-based institutional diagnosis. Chromosomal copy number aberrations
      (CNAs), IDH 1/2 mutations, MGMT promoter methylation, and expression of p53 and
      ATRX were assessed. Survival outcome was compared between the two histological
      groups.Of the 57 codeleted gliomas, 37, 16, and four were classified as
      oligodendroglial, "astrocytic", and unclassified, respectively. Comparative
      genomic hybridization revealed that although chromosome 7q/7 gain was more
      frequent in "astrocytic" gliomas, other CNAs occurred at a similar frequency in
      both groups. None of the "astrocytic" gliomas showed p53 accumulation, and ATRX
      loss was found in three of the 15 "astrocytic" gliomas. The estimated overall
      survival (OS) curves in the patients with codeleted oligodendroglial and
      "astrocytic" gliomas overlapped, and the median OS was 187 and 184 months,
      respectively. Histopathological re-assessment by a single pathologist showed
      consistent results.Gliomas with total 1p19q loss with "astrocytic" features have
      molecular and biological characteristics comparable to those of oligodendroglial
      tumors.

PMID- 25991675
TI  - Identification and evaluation of network modules for the prognosis of basal-like
      breast cancer.
AB  - PURPOSE: Basal-like breast cancer (BLBC) is a molecular subtype of breast cancer
      associated with poor clinical outcome, although some patients with BLBC
      experience long-term survival. Apart from nodal status, current
      clinical/histopathological variables show little capacity to identify BLBC
      patients at either high- or low-risk of disease recurrence. Accordingly, we
      sought to develop a network based genomic predictor for predicting the outcome of
      patients with BLBC. EXPERIMENTAL DESIGN: We performed network analysis on global
      gene expression profiling data of BLBCs, and identified BLBC network modules
      associated with AP-1 transcription, G-protein coupled receptors, and T-, B-, and
      NK-cells that are significant predictors of BLBC patient survival. RESULTS: In
      gene expression and tissue microarray (TMA) validation cohorts of 210 and 102
      BLBC patients, respectively, the identified network modules were robustly
      associated with patient outcome. In the gene expression validation cohort, the
      Kaplan-Meier estimate for 10-year survival in the low-risk group was 90%, whereas
      in the high-risk group it was a 56%. In the TMA cohort, the Kaplan-Meier estimate
      for 10-year survival in the low-risk group was 98%, whereas in the high-risk
      group it was 71%. CONCLUSIONS: The capacity to distinguish between patients with
      BLBC at high- or low-risk of recurrence at the time of diagnosis could permit
      timely intervention with more aggressive therapeutic regimens in those patients
      predicted to be high-risk, and to avoid such therapy in low-risk patients.

PMID- 25991676
TI  - Modulation of miR-21 signaling by MPS1 in human glioblastoma.
AB  - Monopolar spindle 1 (MPS1) is an essential spindle assembly checkpoint (SAC)
      kinase involved in determining spindle integrity. Beyond its mitotic functions,
      it has been implicated in several other signaling pathways. Our earlier studies
      have elaborated on role of MPS1 in glioblastoma (GBM) radiosensitization. In this
      study using reverse phase protein arrays (RPPAs), we assessed MPS1 mediated cell
      signaling pathways and demonstrated that inhibiting MPS1 could upregulate the
      expression of the tumor suppressor PDCD4 and MSH2 genes, by down regulating micro
      RNA-21 (miR-21). In GBMs miR-21 expression is significantly elevated and is
      associated with chemo and radioresistance. Both MPS1 and miR-21 depletion
      suppressed GBM cell proliferation, whereas, ectopic expression of miR-21 rescued
      GBM cell growth from MPS1 inhibition. Further, we demonstrate that MPS1 mediates
      phosphorylation of SMAD3 but not SMAD2 in GBM cells; A possible mechanism behind
      miR-21 modulation by MPS1. Collectively, our results shed light onto an important
      role of MPS1 in TGF-beta/SMAD signaling via miR-21 regulation. We also, show the
      prognostic effect of miR-21, PDCD4 and MSH2 levels to patient survival across
      different GBM molecular subtypes. This scenario in which miR-21 is modulated by
      MPS1 inhibition may be exploited as a potential target for effective GBM therapy.

PMID- 25991677
TI  - Epigenetic age analysis of children who seem to evade aging.
AB  - We previously reported the unusual case of a teenage girl stricken with
      multifocal developmental dysfunctions whose physical development was dramatically
      delayed resulting in her appearing to be a toddler or at best a preschooler, even
      unto the occasion of her death at the age of 20 years. Her life-long physician
      felt that the disorder was unique in the world and that future treatments for age
      related diseases might emerge from its study. The objectives of our research were
      to determine if other such cases exist, and if so, whether aging is actually
      slowed. Of seven children characterized by dramatically slow developmental rates,
      five also had associated disorders displayed by the first case. All of the
      identified subjects were female. To objectively measure the age of blood tissue
      from these subjects, we used a highly accurate biomarker of aging known as
      "epigenetic clock" based on DNA methylation levels. No statistically significant
      differences in chronological and epigenetic ages were detected in any of the
      newly discovered cases. 

PMID- 25991678
TI  - The bamboo-eating giant panda harbors a carnivore-like gut microbiota, with
      excessive seasonal variations.
AB  - The giant panda evolved from omnivorous bears. It lives on a bamboo-dominated
      diet at present, but it still retains a typical carnivorous digestive system and
      is genetically deficient in cellulose-digesting enzymes. To find out whether this
      endangered mammalian species, like other herbivores, has successfully developed a
      gut microbiota adapted to its fiber-rich diet, we conducted a 16S rRNA gene-based
      large-scale structural profiling of the giant panda fecal microbiota. Forty-five
      captive individuals were sampled in spring, summer, and late autumn within 1
      year. Significant intraindividual variations in the diversity and structure of
      gut microbiota across seasons were observed in this population, which were even
      greater than the variations between individuals. Compared with published data
      sets involving 124 gut microbiota profiles from 54 mammalian species, these giant
      pandas, together with 9 captive and 7 wild individuals investigated previously,
      showed extremely low gut microbiota diversity and an overall structure that
      diverged from those of nonpanda herbivores but converged with those of
      carnivorous and omnivorous bears. The giant panda did not harbor putative
      cellulose-degrading phylotypes such as Ruminococcaceae and Bacteroides bacteria
      that are typically enriched in other herbivores, but instead, its microbiota was
      dominated by Escherichia/Shigella and Streptococcus bacteria. Members of the
      class Clostridia were common and abundant in the giant panda gut microbiota, but
      most of the members present were absent in other herbivores and were not
      phylogenetically related with known cellulolytic lineages. Therefore, the giant
      panda appears not to have evolved a gut microbiota compatible with its newly
      adopted diet, which may adversely influence the coevolutionary fitness of this
      herbivore. IMPORTANCE: The giant panda, an endangered mammalian species endemic
      to western China, is well known for its unique bamboo diet. Unlike other
      herbivores that have successfully evolved anatomically specialized digestive
      systems to efficiently deconstruct fibrous plant matter, the giant panda still
      retains a gastrointestinal tract typical of carnivores. We characterized the
      fecal bacterial communities from a giant panda population to determine whether
      this animal relies on its symbiotic gut microbiota to cope with the complex
      carbohydrates that dominate its diet, as is common in other herbivores. We found
      that the giant panda gut microbiota is low in diversity and highly variable
      across seasons. It also shows an overall composition typical of bears and
      entirely differentiated from other herbivores, with low levels of putative
      cellulose-digesting bacteria. The gut microbiota of this herbivore, therefore,
      may not have well adapted to its highly fibrous diet, suggesting a potential link
      with its poor digestive efficiency.

PMID- 25991679
TI  - Patterns in wetland microbial community composition and functional gene
      repertoire associated with methane emissions.
AB  - Wetland restoration on peat islands previously drained for agriculture has
      potential to reverse land subsidence and sequester atmospheric carbon dioxide as
      peat accretes. However, the emission of methane could potentially offset the
      greenhouse gas benefits of captured carbon. As microbial communities play a key
      role in governing wetland greenhouse gas fluxes, we are interested in how
      microbial community composition and functions are associated with wetland
      hydrology, biogeochemistry, and methane emission, which is critical to modeling
      the microbial component in wetland methane fluxes and to managing restoration
      projects for maximal carbon sequestration. Here, we couple sequence-based methods
      with biogeochemical and greenhouse gas measurements to interrogate microbial
      communities from a pilot-scale restored wetland in the Sacramento-San Joaquin
      Delta of California, revealing considerable spatial heterogeneity even within
      this relatively small site. A number of microbial populations and functions
      showed strong correlations with electron acceptor availability and methane
      production; some also showed a preference for association with plant roots.
      Marker gene phylogenies revealed a diversity of major methane-producing and 
      consuming populations and suggested novel diversity within methanotrophs.
      Methanogenic archaea were observed in all samples, as were nitrate-, sulfate-,
      and metal-reducing bacteria, indicating that no single terminal electron acceptor
      was preferred despite differences in energetic favorability and suggesting
      spatial microheterogeneity and microniches. Notably, methanogens were negatively
      correlated with nitrate-, sulfate-, and metal-reducing bacteria and were most
      abundant at sampling sites with high peat accretion and low electron acceptor
      availability, where methane production was highest. IMPORTANCE: Wetlands are the
      largest nonanthropogenic source of atmospheric methane but also a key global
      carbon reservoir. Characterizing belowground microbial communities that mediate
      carbon cycling in wetlands is critical to accurately predicting their responses
      to changes in land management and climate. Here, we studied a restored wetland
      and revealed substantial spatial heterogeneity in biogeochemistry, methane
      production, and microbial communities, largely associated with the wetland
      hydraulic design. We observed patterns in microbial community composition and
      functions correlated with biogeochemistry and methane production, including
      diverse microorganisms involved in methane production and consumption. We found
      that methanogenesis gene abundance is inversely correlated with genes from
      pathways exploiting other electron acceptors, yet the ubiquitous presence of
      genes from all these pathways suggests that diverse electron acceptors contribute
      to the energetic balance of the ecosystem. These investigations represent an
      important step toward effective management of wetlands to reduce methane flux to
      the atmosphere and enhance belowground carbon storage.

PMID- 25991680
TI  - The Bacterium Frischella perrara Causes Scab Formation in the Gut of its Honeybee
      Host.
AB  - Honeybees harbor well-defined bacterial communities in their guts. The major
      members of these communities appear to benefit the host, but little is known
      about how they interact with the host and specifically how they interface with
      the host immune system. In the pylorus, a short region between the midgut and
      hindgut, honeybees frequently exhibit scab-like structures on the epithelial gut
      surface. These structures are reminiscent of a melanization response of the
      insect immune system. Despite the wide distribution of this phenotype in honeybee
      populations, its cause has remained elusive. Here, we show that the presence of a
      common member of the bee gut microbiota, the gammaproteobacterium Frischella
      perrara, correlates with the appearance of the scab phenotype. Bacterial
      colonization precedes scab formation, and F. perrara specifically localizes to
      the melanized regions of the host epithelium. Under controlled laboratory
      conditions, we demonstrate that exposure of microbiota-free bees to F. perrara
      but not to other bacteria results in scab formation. This shows that F. perrara
      can become established in a spatially restricted niche in the gut and triggers a
      morphological change of the epithelial surface, potentially due to a host immune
      response. As an intermittent colonizer, this bacterium holds promise for
      addressing questions of community invasion in a simple yet relevant model system.
      Moreover, our results show that gut symbionts of bees engage in differential host
      interactions that are likely to affect gut homeostasis. Future studies should
      focus on how these different gut bacteria impact honeybee health. IMPORTANCE: As
      pollinators, honeybees are key species for agricultural and natural ecosystems.
      Their guts harbor simple communities composed of characteristic bacterial
      species. Because of these features, bees are ideal systems for studying
      fundamental aspects of gut microbiota-host interactions. However, little is known
      about how these bacteria interact with their host. Here, we show that a common
      member of the bee gut microbiota causes the formation of a scab-like structure on
      the gut epithelium of its host. This phenotype was first described in 1946, but
      since then it has not been much further characterized, despite being found in bee
      populations worldwide. The scab phenotype is reminiscent of melanization, a
      conserved innate immune response of insects. Our results show that high abundance
      of one member of the bee gut microbiota triggers this specific phenotype,
      suggesting that the gut microbiota composition can affect the immune status of
      this key pollinator species.

PMID- 25991681
TI  - Synthetic and Evolutionary Construction of a Chlorate-Reducing Shewanella
      oneidensis MR-1.
AB  - Despite evidence for the prevalence of horizontal gene transfer of respiratory
      genes, little is known about how pathways functionally integrate within new
      hosts. One example of a mobile respiratory metabolism is bacterial chlorate
      reduction, which is frequently encoded on composite transposons. This implies
      that the essential components of the metabolism are encoded on these mobile
      elements. To test this, we heterologously expressed genes for chlorate reduction
      from Shewanella algae ACDC in the non-chlorate-reducing Shewanella oneidensis MR
      1. The construct that ultimately endowed robust growth on chlorate included cld,
      a cytochrome c gene, clrABDC, and two genes of unknown function. Although strain
      MR-1 was unable to grow on chlorate after initial insertion of these genes into
      the chromosome, 11 derived strains capable of chlorate respiration were obtained
      through adaptive evolution. Genome resequencing indicated that all of the evolved
      chlorate-reducing strains replicated a large genomic region containing chlorate
      reduction genes. Contraction in copy number and loss of the ability to reduce
      chlorate were also observed, indicating that this phenomenon was extremely
      dynamic. Although most strains contained more than six copies of the replicated
      region, a single strain with less duplication also grew rapidly. This strain
      contained three additional mutations that we hypothesized compensated for the low
      copy number. We remade the mutations combinatorially in the unevolved strain and
      determined that a single nucleotide polymorphism (SNP) upstream of cld enabled
      growth on chlorate and was epistatic to a second base pair change in the NarP
      binding sequence between narQP and nrfA that enhanced growth. IMPORTANCE: The
      ability of chlorate reduction composite transposons to form functional
      metabolisms after transfer to a new host is an important part of their
      propagation. To study this phenomenon, we engineered Shewanella oneidensis MR-1
      into a chlorate reducer. We defined a set of genes sufficient to endow growth on
      chlorate from a plasmid, but found that chromosomal insertion of these genes was
      nonfunctional. Evolution of this inoperative strain into a chlorate reducer
      showed that tandem duplication was a dominant mechanism of activation. While copy
      number changes are a relatively rapid way of increasing gene dosage, replicating
      almost 1 megabase of extra DNA is costly. Mutations that alleviate the need for
      high copy number are expected to arise and eventually predominate, and we
      identified a single nucleotide polymorphism (SNP) that relieved the copy number
      requirement. This study uses both rational and evolutionary approaches to gain
      insight into the evolution of a fascinating respiratory metabolism.

PMID- 25991682
TI  - Gut microbial succession follows acute secretory diarrhea in humans.
AB  - Disability after childhood diarrhea is an important burden on global
      productivity. Recent studies suggest that gut bacterial communities influence how
      humans recover from infectious diarrhea, but we still lack extensive data and
      mechanistic hypotheses for how these bacterial communities respond to diarrheal
      disease and its treatment. Here, we report that after Vibrio cholerae infection,
      the human gut microbiota undergoes an orderly and reproducible succession that
      features transient reversals in relative levels of enteric Bacteroides and
      Prevotella. Elements of this succession may be a common feature in microbiota
      recovery from acute secretory diarrhea, as we observed similar successional
      dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic
      analyses suggest that multiple mechanisms drive microbial succession after
      cholera, including bacterial dispersal properties, changing enteric oxygen and
      carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after
      cholera may be predictable at the level of community structure but is driven by a
      complex set of temporally varying ecological processes. Our findings suggest
      opportunities for diagnostics and therapies targeting the gut microbiota in
      humans recovering from infectious diarrhea. IMPORTANCE: Disability after diarrhea
      is a major burden on public health in the developing world. Gut bacteria may
      affect this recovery, but it remains incompletely understood how resident
      microbes in the digestive tract respond to diarrheal illness. Here, we observed
      an orderly and reproducible succession of gut bacterial groups after cholera in
      humans. Genomic analyses associated the succession with bacterial dispersal in
      food, an altered microbial environment, and changing phage levels. Our findings
      suggest that it may one day be feasible to manage resident bacterial populations
      in the gut after infectious diarrhea.

PMID- 25991683
TI  - Clostridium clariflavum: Key Cellulosome Players Are Revealed by Proteomic
      Analysis.
AB  - Clostridium clariflavum is an anaerobic, cellulosome-forming thermophile,
      containing in its genome genes for a large number of cellulosomal enzyme and a
      complex scaffoldin system. Previously, we described the major cohesin-dockerin
      interactions of the cellulosome components, and on this basis a model of diverse
      cellulosome assemblies was derived. In this work, we cultivated C. clariflavum on
      cellobiose-, microcrystalline cellulose-, and switchgrass-containing media and
      isolated cell-free cellulosome complexes from each culture. Gel filtration
      separation of the cellulosome samples revealed two major fractions, which were
      analyzed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      in order to identify the key players of the cellulosome assemblies therein. From
      the 13 scaffoldins present in the C. clariflavum genome, 11 were identified, and
      a variety of enzymes from different glycoside hydrolase and carbohydrate esterase
      families were identified, including the glycoside hydrolase families GH48, GH9,
      GH5, GH30, GH11, and GH10. The expression level of the cellulosomal proteins
      varied as a function of the carbon source used for cultivation of the bacterium.
      In addition, the catalytic activity of each cellulosome was examined on different
      cellulosic substrates, xylan and switchgrass. The cellulosome isolated from the
      microcrystalline cellulose-containing medium was the most active of all the
      cellulosomes that were tested. The results suggest that the expression of the
      cellulosome proteins is regulated by the type of substrate in the growth medium.
      Moreover, both cell-free and cell-bound cellulosome complexes were produced which
      together may degrade the substrate in a synergistic manner. These observations
      are compatible with our previously published model of cellulosome assemblies in
      this bacterium. IMPORTANCE: Because the reservoir of unsustainable fossil fuels,
      such as coal, petroleum, and natural gas, is overutilized and continues to
      contribute to environmental pollution and CO2 emission, the need for appropriate
      alternative energy sources becomes more crucial. Bioethanol produced from
      dedicated crops and cellulosic waste can provide a partial answer, yet a cost
      effective production method must be developed. The cellulosome system of the
      anaerobic thermophile C. clariflavum comprises a large number of cellulolytic and
      hemicellulolytic enzymes, which self-assemble in a number of different
      cellulosome architectures for enhanced cellulosic biomass degradation.
      Identification of the major cellulosomal components expressed during growth of
      the bacterium and their influence on its catalytic capabilities provide insight
      into the performance of the remarkable cellulosome of this intriguing bacterium.
      The findings, together with the thermophilic characteristics of the proteins,
      render C. clariflavum of great interest for future use in industrial cellulose
      conversion processes.

PMID- 25991684
TI  - Reinforcing Lipid A Acylation on the Cell Surface of Acinetobacter baumannii
      Promotes Cationic Antimicrobial Peptide Resistance and Desiccation Survival.
AB  - Acinetobacter baumannii is an emerging Gram-negative pathogen found in hospitals
      and intensive care units. In order to persist in hospital environments, A.
      baumannii withstands desiccative conditions and can rapidly develop multidrug
      resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs)
      have served as therapeutic alternatives because they target the conserved lipid A
      component of the Gram-negative outer membrane to lyse the bacterial cell.
      However, many Gram-negative pathogenic bacteria, including A. baumannii, fortify
      their outer membrane with hepta-acylated lipid A to protect the cell from CAMP
      dependent cell lysis. Whereas in Escherichia coli and Salmonella, increased
      production of the outer membrane acyltransferase PagP results in formation of
      protective hepta-acylated lipid A, which reinforces the lipopolysaccharide
      portion of the outer membrane barrier, A. baumannii does not carry a gene that
      encodes a PagP homolog. Instead, A. baumannii has evolved a PagP-independent
      mechanism to synthesize protective hepta-acylated lipid A. Taking advantage of a
      recently adapted A. baumannii genetic recombineering system, we characterized two
      putative acyltransferases in A. baumannii designated LpxLAb (A. baumannii LpxL)
      and LpxMAb (A. baumannii LpxM), which transfer one and two lauroyl (C12:0) acyl
      chains, respectively, during lipid A biosynthesis. Hepta-acylation of A.
      baumannii lipid A promoted resistance to vertebrate and polymyxin CAMPs, which
      are prescribed as last-resort treatment options. Intriguingly, our analysis also
      showed that LpxMAb-dependent acylation of lipid A is essential for A. baumannii
      desiccation survival, a key resistance mechanism for survival in hospital
      environments. Compounds that inhibit LpxMAb-dependent hepta-acylation of lipid A
      could act synergistically with CAMPs to provide innovative transmission
      prevention strategies and treat multidrug-resistant infections. IMPORTANCE:
      Acinetobacter baumannii infections can be life threatening, and disease can
      progress in a variety of host tissues. Current antibiotic regimen and
      disinfectant strategies have failed to limit nosocomial A. baumannii infections.
      Instead, the rate of A. baumannii infection among health care communities has
      skyrocketed due to the bacterium's adaptability. Its aptitude for survival over
      extended periods on inanimate objects, such as catheters, respirators, and
      surfaces in intensive care units, or on the hands of health care workers and its
      ability to rapidly develop antibiotic resistance make A. baumannii a threat to
      health care communities. Emergence of multidrug- and extremely drug-resistant A.
      baumannii illustrates the ineffectiveness of current prevention and treatment
      options. Our analysis to understand how A. baumannii resists cationic
      antimicrobial peptide (CAMP)-mediated and desiccative killing revealed two lipid
      A acyltransferases that produce protective hepta-acylated lipid A. Our work
      suggests that inhibiting lipid A biosynthesis by targeting the acyltransferase
      LpxMAb (A. baumannii LpxM) could provide a novel target to combat this pathogen.

PMID- 25991685
TI  - A novel pathogenic Mammalian orthoreovirus from diarrheic pigs and Swine blood
      meal in the United States.
AB  - Since May 2013, outbreaks of porcine epidemic diarrhea have devastated the U.S.
      swine industry, causing immense economic losses. Two different swine enteric
      coronaviruses (porcine epidemic diarrhea virus and Delta coronavirus) have been
      isolated from the affected swine population. The disease has been reported from
      at least 32 states of the United States and other countries, including Mexico,
      Peru, Dominican Republic, Canada, Columbia, Ecuador, and Ukraine, with repeated
      outbreaks in previously infected herds. Here we report the isolation and
      characterization of a novel mammalian orthoreovirus 3 (MRV3) from diarrheic feces
      of piglets from these outbreaks in three states and ring-dried swine blood meal
      from multiple sources. MRV3 could not be isolated from healthy or pigs that had
      recovered from epidemic diarrhea from four states. Several MRV3 isolates were
      obtained from chloroform-extracted pig feces or blood meal in cell cultures or
      developing chicken embryos. Biological characterization of two representative
      isolates revealed trypsin resistance and thermostability at 90 degrees C. NextGen
      sequencing of ultrapurified viruses indicated a strong homology of the S1 segment
      to mammalian and bat MRV3. Neonatal piglets experimentally infected with these
      viruses or a chloroform extract of swine blood meal developed severe diarrhea and
      acute gastroenteritis with 100% mortality within 3 days postinfection. Therefore,
      the novel porcine MRV3 may contribute to enteric disease along with other swine
      enteric viruses. The role of MRV3 in the current outbreaks of porcine epidemic
      diarrhea in the United States remains to be determined, but the pathogenic nature
      of the virus warrants further investigations on its epidemiology and prevalence.
      IMPORTANCE: Porcine orthoreoviruses causing diarrhea have been reported in China
      and Korea but not in the United States. We have isolated and characterized two
      pathogenic reassortant MRV3 isolates from swine fecal samples from porcine
      epidemic diarrhea outbreaks and ring-dried swine blood meal in the United States.
      These fecal and blood meal isolates or a chloroform extract of blood meal induced
      severe diarrhea and mortality in experimentally infected neonatal pigs. Genetic
      and phylogenetic analyses of two MRV3 isolates revealed that they are identical
      but differed significantly from nonpathogenic mammalian orthoreoviruses
      circulating in the United States. The present study provides a platform for
      immediate development of suitable vaccines and diagnostics to prevent and control
      porcine orthoreovirus diarrhea.

PMID- 25991686
TI  - Genome-Wide siRNA Screen Identifies Complementary Signaling Pathways Involved in
      Listeria Infection and Reveals Different Actin Nucleation Mechanisms during
      Listeria Cell Invasion and Actin Comet Tail Formation.
AB  - Listeria monocytogenes enters nonphagocytic cells by a receptor-mediated
      mechanism that is dependent on a clathrin-based molecular machinery and actin
      rearrangements. Bacterial intra- and intercellular movements are also actin
      dependent and rely on the actin nucleating Arp2/3 complex, which is activated by
      host-derived nucleation-promoting factors downstream of the cell receptor Met
      during entry and by the bacterial nucleation-promoting factor ActA during comet
      tail formation. By genome-wide small interfering RNA (siRNA) screening for host
      factors involved in bacterial infection, we identified diverse cellular signaling
      networks and protein complexes that support or limit these processes. In
      addition, we could precise previously described molecular pathways involved in
      Listeria invasion. In particular our results show that the requirements for actin
      nucleators during Listeria entry and actin comet tail formation are different.
      Knockdown of several actin nucleators, including SPIRE2, reduced bacterial
      invasion while not affecting the generation of comet tails. Most interestingly,
      we observed that in contrast to our expectations, not all of the seven subunits
      of the Arp2/3 complex are required for Listeria entry into cells or actin tail
      formation and that the subunit requirements for each of these processes differ,
      highlighting a previously unsuspected versatility in Arp2/3 complex composition
      and function. IMPORTANCE: Listeria is a bacterial pathogen that induces its
      internalization within the cytoplasm of human cells and has been used for decades
      as a major molecular tool to manipulate cells in order to explore and discover
      cellular functions. We have inactivated individually, for the first time in
      epithelial cells, all the genes of the human genome to investigate whether each
      gene modifies positively or negatively the Listeria infectious process. We
      identified novel signaling cascades that have never been associated with Listeria
      infection. We have also revisited the role of the molecular complex Arp2/3
      involved in the polymerization of the actin cytoskeleton, which was shown
      previously to be required for Listeria entry and movement inside host cells, and
      we demonstrate that contrary to the general dogma, some subunits of the complex
      are dispensable for both Listeria entry and bacterial movement.

PMID- 25991687
TI  - A Combined Omics Approach to Generate the Surface Atlas of Human Naive CD4+ T
      Cells during Early T-Cell Receptor Activation.
AB  - Naive CD4(+) T cells are the common precursors of multiple effector and memory T
      cell subsets and possess a high plasticity in terms of differentiation potential.
      This stem-cell-like character is important for cell therapies aiming at
      regeneration of specific immunity. Cell surface proteins are crucial for
      recognition and response to signals mediated by other cells or environmental
      changes. Knowledge of cell surface proteins of human naive CD4(+) T cells and
      their changes during the early phase of T-cell activation is urgently needed for
      a guided differentiation of naive T cells and may support the selection of
      pluripotent cells for cell therapy. Periodate oxidation and aniline-catalyzed
      oxime ligation technology was applied with subsequent quantitative liquid
      chromatography-tandem MS to generate a data set describing the surface proteome
      of primary human naive CD4(+) T cells and to monitor dynamic changes during the
      early phase of activation. This led to the identification of 173 N-glycosylated
      surface proteins. To independently confirm the proteomic data set and to analyze
      the cell surface by an alternative technique a systematic phenotypic expression
      analysis of surface antigens via flow cytometry was performed. This screening
      expanded the previous data set, resulting in 229 surface proteins, which were
      expressed on naive unstimulated and activated CD4(+) T cells. Furthermore, we
      generated a surface expression atlas based on transcriptome data, experimental
      annotation, and predicted subcellular localization, and correlated the proteomics
      result with this transcriptional data set. This extensive surface atlas provides
      an overall naive CD4(+) T cell surface resource and will enable future studies
      aiming at a deeper understanding of mechanisms of T-cell biology allowing the
      identification of novel immune targets usable for the development of therapeutic
      treatments. 

PMID- 25991688
TI  - The Impact II, a Very High-Resolution Quadrupole Time-of-Flight Instrument (QTOF)
      for Deep Shotgun Proteomics.
AB  - Hybrid quadrupole time-of-flight (QTOF) mass spectrometry is one of the two major
      principles used in proteomics. Although based on simple fundamentals, it has over
      the last decades greatly evolved in terms of achievable resolution, mass
      accuracy, and dynamic range. The Bruker impact platform of QTOF instruments takes
      advantage of these developments and here we develop and evaluate the impact II
      for shotgun proteomics applications. Adaption of our heated liquid chromatography
      system achieved very narrow peptide elution peaks. The impact II is equipped with
      a new collision cell with both axial and radial ion ejection, more than doubling
      ion extraction at high tandem MS frequencies. The new reflectron and detector
      improve resolving power compared with the previous model up to 80%, i.e. to
      40,000 at m/z 1222. We analyzed the ion current from the inlet capillary and
      found very high transmission (>80%) up to the collision cell. Simulation and
      measurement indicated 60% transfer into the flight tube. We adapted MaxQuant for
      QTOF data, improving absolute average mass deviations to better than 1.45 ppm.
      More than 4800 proteins can be identified in a single run of HeLa digest in a 90
      min gradient. The workflow achieved high technical reproducibility (R2 > 0.99)
      and accurate fold change determination in spike-in experiments in complex
      mixtures. Using label-free quantification we rapidly quantified haploid against
      diploid yeast and characterized overall proteome differences in mouse cell lines
      originating from different tissues. Finally, after high pH reversed-phase
      fractionation we identified 9515 proteins in a triplicate measurement of HeLa
      peptide mixture and 11,257 proteins in single measurements of cerebellum-the
      highest proteome coverage reported with a QTOF instrument so far. 

PMID- 25991692
TI  - A randomized, double-blind, placebo-controlled, clinical study on the efficacy
      and safety of calcium dobesilate in the treatment of chronic venous
      insufficiency.
AB  - OBJECTIVE: To show the superiority of 500 mg calcium dobesilate vs. placebo in
      reduction of edema of the lower limbs in patients with chronic venous
      insufficiency, Clinical, Etiological, Anatomical and Pathophysiological classes
      C3/C4. METHODS: A total of 351 patients were randomized (n = 174 calcium
      dobesilate, n = 177 placebo). Active treatment was 500 mg calcium dobesilate,
      three times daily for 12 weeks, with a 12-week follow-up. RESULTS: At the end of
      treatment, the relative volume change in the most pathological leg was -0.6 +/-
      4.8% with calcium dobesilate compared to -0.3 +/- 3.3% with placebo (p = 0.09).
      At the end of follow-up, this was -1.01 +/- 5.4% for calcium dobesilate vs. -0.08
      +/- 3.5% for placebo (p = 0.002). CONCLUSIONS: Calcium dobesilate treatment
      resulted in no significant volume change in the most pathological leg between
      baseline and end of treatment. However, the calcium dobesilate group showed a
      significantly greater volume decrease in the most pathological leg at the end of
      follow-up. Calcium dobesilate was well-tolerated, with a safety profile
      consistent with previously published data.

PMID- 25991694
TI  - Livestock models in translational medicine.
AB  - This issue of the ILAR Journal focuses on livestock models in translational
      medicine. Livestock models of selected human diseases present important
      advantages as compared with rodent models for translating fundamental
      breakthroughs in biology to useful preventatives and therapeutics for humans.
      Livestock reflect the complexity of applying medical advances in an outbred
      species. In many cases, the pathogenesis of infectious, metabolic, genetic, and
      neoplastic diseases in livestock species more closely resembles that in humans
      than does the pathogenesis of rodent models. Livestock models also provide the
      advantage of similar organ size and function and the ability to serially sample
      an animal throughout the study period. Research using livestock models for human
      disease often benefits not only human health but animal health and food
      production as well. This issue of the ILAR Journal presents information on
      translational research using livestock models in two broad areas: microbiology
      and infectious disease (transmissible spongiform encephalopathies, mycobacterial
      infections, influenza A virus infection, vaccine development and testing, the
      human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell
      therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular
      dystrophy, wound healing). In addition, there is a manuscript devoted to
      Institutional Animal Care and Use Committees' responsibilities for reviewing
      research using livestock models. Conducting translational research using
      livestock models requires special facilities and researchers with expertise in
      livestock. There are many institutions in the world with experienced researchers
      and facilities designed for livestock research; primarily associated with
      colleges of agriculture and veterinary medicine or government laboratories. 

PMID- 25991693
TI  - Limited genetic diversity and extensive antimicrobial resistance in clinical
      isolates of Acinetobacter baumannii in north-east Iran.
AB  - This study determined the mechanisms and patterns of antimicrobial resistance
      among the isolates obtained from different wards of a teaching hospital in the
      city of Mashhad in north-east Iran. Between January 2012 and the end of June
      2012, 36 isolates of Acinetobacter baumannii were collected from different wards
      of Ghaem Hospital. Antimicrobial susceptibility testing and epsilometer testing
      (E-test) were performed. The genetic resistance determinants of A, B and D
      classes of beta-lactamases, aminoglycoside modifying enzymes (AMEs), efflux pumps
      and ISAba1 elements were assessed by PCR. Repetitive extragenic palindromic
      element (REP)-PCR was performed to find the genetic relatedness of the isolates.
      Colistin was the most effective antibiotic of those tested, where all isolates
      were susceptible. E-test results revealed high rates of resistance to imipenem,
      ceftazidime and ciprofloxacin. The majority of isolates (97  %) were multidrug
      resistant. OXA-51, OXA-23 and tetB genes were detected in all isolates, but OXA
      58, IMP and tetA were not detected. The prevalence of OXA-24, bla(TEM), bla(ADC),
      bla(VIM) and adeB were 64, 95, 61, 64 and 86  %, respectively. ISAba1 was found
      to be inserted into the 5' end of OXA-23 in 35 isolates (97  %). Of the AMEs,
      aadA1 (89  %) was the most prevalent, followed by aphA1 (75  %). The band
      patterns reproduced by REP-PCR showed that 34 out of 36 isolates belonged to one
      clone and two singletons were identified. The results confirmed that refractory
      A. baumannii isolates were widely distributed and warned the hospital infection
      control team to exert strict measures to control the infection. An urgent
      surveillance system should be implemented.

PMID- 25991695
TI  - The transmissible spongiform encephalopathies of livestock.
AB  - Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal
      protein-misfolding neurodegenerative diseases. TSEs have been described in
      several species, including bovine spongiform encephalopathy (BSE) in cattle,
      scrapie in sheep and goats, chronic wasting disease (CWD) in cervids,
      transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob
      disease (CJD) in humans. These diseases are associated with the accumulation of a
      protease-resistant, disease-associated isoform of the prion protein (called
      PrP(Sc)) in the central nervous system and other tissues, depending on the host
      species. Typically, TSEs are acquired through exposure to infectious material,
      but inherited and spontaneous TSEs also occur. All TSEs share pathologic features
      and infectious mechanisms but have distinct differences in transmission and
      epidemiology due to host factors and strain differences encoded within the
      structure of the misfolded prion protein. The possibility that BSE can be
      transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has
      brought attention to this family of diseases. This review is focused on the TSEs
      of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and
      goats. 

PMID- 25991696
TI  - Mycobacterium bovis Infection of Cattle and White-Tailed Deer: Translational
      Research of Relevance to Human Tuberculosis.
AB  - Tuberculosis (TB) is a premier example of a disease complex with pathogens
      primarily affecting humans (i.e., Mycobacterium tuberculosis) or livestock and
      wildlife (i.e., Mycobacterium bovis) and with a long history of inclusive
      collaborations between physicians and veterinarians. Advances in the study of
      bovine TB have been applied to human TB, and vice versa. For instance, landmark
      discoveries on the use of Koch's tuberculin and interferon-gamma release assays
      for diagnostic purposes, as well as Calmette and Guerin's attenuated M. bovis
      strain as a vaccine, were first evaluated in cattle for control of bovine TB
      prior to wide-scale use in humans. Likewise, recent discoveries on the role of
      effector/memory T cell subsets and polyfunctional T cells in the immune response
      to human TB, particularly as related to vaccine efficacy, have paved the way for
      similar studies in cattle. Over the past 15 years, substantial funding for
      development of human TB vaccines has led to the emergence of multiple promising
      candidates now in human clinical trials. Several of these vaccines are being
      tested for immunogenicity and efficacy in cattle. Also, the development of
      population-based vaccination strategies for control of M. bovis infection in
      wildlife reservoirs will undoubtedly have an impact on our understanding of herd
      immunity with relevance to the control of both bovine and human TB in regions of
      the world with high prevalence of TB. Thus, the one-health approach to research
      on TB is mutually beneficial for our understanding and control of TB in humans,
      livestock, and wildlife. 

PMID- 25991697
TI  - Swine as a model for influenza A virus infection and immunity.
AB  - Influenza A viruses (IAVs) infect a variety of hosts, including humans, swine,
      and various avian species. The annual influenza disease burden in the human
      population remains significant even with current vaccine usage, and much about
      the pathogenesis and transmission of influenza viruses in humans remains unclear.
      Thus, animal models are a fundamental tool for influenza research to understand
      mechanisms of virulence and to develop more efficacious vaccines and forms of
      prevention or treatment. The choice of experimental model to be used should be
      based on the species characteristics and similarities to humans, and how the
      limitations of each host interfere the least with the parameters studied.
      Influenza virus infection in swine has many similarities with that in humans: the
      same subtypes are endemic in both species, there has been repeated exchange of
      viruses between these hosts, the clinical manifestation and pathogenesis are
      similar, and there is a similar distribution of IAV receptors in the respiratory
      tract. Considering these common characteristics, and the similarities between
      humans and swine in terms of genetics, anatomy, and physiology, pigs represent an
      excellent yet often overlooked model for biomedical research and the study of IAV
      infection. 

PMID- 25991698
TI  - Large animal models for vaccine development and testing.
AB  - The development of human vaccines continues to rely on the use of animals for
      research. Regulatory authorities require novel vaccine candidates to undergo
      preclinical assessment in animal models before being permitted to enter the
      clinical phase in human subjects. Substantial progress has been made in recent
      years in reducing and replacing the number of animals used for preclinical
      vaccine research through the use of bioinformatics and computational biology to
      design new vaccine candidates. However, the ultimate goal of a new vaccine is to
      instruct the immune system to elicit an effective immune response against the
      pathogen of interest, and no alternatives to live animal use currently exist for
      evaluation of this response. Studies identifying the mechanisms of immune
      protection; determining the optimal route and formulation of vaccines;
      establishing the duration and onset of immunity, as well as the safety and
      efficacy of new vaccines, must be performed in a living system. Importantly, no
      single animal model provides all the information required for advancing a new
      vaccine through the preclinical stage, and research over the last two decades has
      highlighted that large animals more accurately predict vaccine outcome in humans
      than do other models. Here we review the advantages and disadvantages of large
      animal models for human vaccine development and demonstrate that much of the
      success in bringing a new vaccine to market depends on choosing the most
      appropriate animal model for preclinical testing. 

PMID- 25991699
TI  - Human microbiota-associated swine: current progress and future opportunities.
AB  - Gnotobiotic (GN) rodent models have provided insight into the contributions of
      the gut microbiota to host health and preventing disease. However, rodent models
      are limited by several important physiological and metabolic differences from
      humans, and many rodent models do not dependably replicate the clinical
      manifestations of human diseases. Due to the high degree of similarity in
      anatomy, physiology, immunology and brain growth, the domestic pig (Sus scrofa)
      is considered a clinically relevant model to study factors influencing human
      gastrointestinal, immune, and brain development. Gnotobiotic piglet models have
      been developed and shown to recapitulate key aspects of GN rodent models. Human
      microbiota-associated (HMA) piglets have been established using inocula from
      infants, children, and adults. The gut microbiota of recipient HMA piglets was
      more similar to that of the human donor than that of conventionally reared
      piglets harboring a pig microbiota. Moreover, Bifidobacterium and Bacteroides,
      two predominant bacterial groups of infant gut, were successfully established in
      the HMA piglets. Thus, the HMA pig model has the potential to be a valuable model
      for investigating how the gut microbiota composition changes in response to
      environmental factors, such as age, diet, vaccination, antibiotic use and
      infection. The HMA also represents a robust model for screening the efficacy of
      pre- and probiotic interventions. Lastly, HMA piglets can be an ideal model with
      which to elucidate microbe-host interactions in human health and disease due to
      the similarities to humans in anatomy, physiology, developmental maturity at
      birth, and the pathophysiology of many human diseases. 

PMID- 25991700
TI  - Livestock models for exploiting the promise of pluripotent stem cells.
AB  - Livestock species are widely used as biomedical models. Pigs, in particular, are
      beginning to have a significant role in regenerative medicine for testing the
      applicability, success, and safety of grafts derived from induced pluripotent
      stem cells. Animal testing must always be performed before any clinical trials
      are performed in humans, and pigs may sometimes be the species of choice because
      of their physiological and anatomical similarities to humans. Induced pluripotent
      stem cells (iPSC) have been generated with some success from livestock species by
      a variety of reprogramming procedures, but authenticated embryonic stem cells
      (ESC) have not. There are now several studies in which porcine iPSC have been
      tested for their ability to provide functional grafts in pigs. Pigs have also
      served as recipients for grafts derived from human iPSC. There have also been
      recent advances in creating pigs with severe combined immunodeficiency (SCID).
      Like SCID mice, these pigs are expected to be graft tolerant. Additionally,
      chimeric, partially humanized pigs could be sources of human organs. Another
      potential application of pluripotent stem cells from livestock is for the purpose
      of differentiating the cells into skeletal muscle, which, in turn, could be used
      either to produce cultured meat or to engraft into damaged muscle. None of these
      technologies has advanced to a stage that they have become mainstream, however.
      Despite the value of livestock models in regenerative medicine, only a limited
      number of institutions are able to use these animals. 

PMID- 25991702
TI  - Ovine pulmonary adenocarcinoma: a large animal model for human lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. Recent progress in
      understanding the molecular pathogenesis of this disease has resulted in novel
      therapeutic strategies targeting specific groups of patients. Further studies are
      required to provide additional advances in diagnosis and treatment. Animal models
      are valuable tools for studying oncogenesis in lung cancer, particularly during
      the early stages of disease where tissues are rarely available from human cases.
      Mice have traditionally been used for studying lung cancer in vivo, and a variety
      of spontaneous and transgenic models are available. However, it is recognized
      that other species may also be informative for studies of cancer. Ovine pulmonary
      adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by
      retrovirus infection and has several features in common with adenocarcinoma of
      humans, including a similar histological appearance and activation of common cell
      signaling pathways. Additionally, the size and organization of human lungs are
      much closer to those of sheep lungs than to those of mice, which facilitates
      experimental approaches in sheep that are not available in mice. Thus OPA
      presents opportunities for studying lung tumor development that can complement
      conventional murine models. Here we describe the potential applications of OPA as
      a model for human lung adenocarcinoma with an emphasis on the various in vivo and
      in vitro experimental systems available. 

PMID- 25991701
TI  - Beyond the mouse monopoly: studying the male germ line in domestic animal models.
AB  - Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis and
      essential to maintain the continuous production of spermatozoa after the onset of
      puberty in the male. The study of the male germ line is important for
      understanding the process of spermatogenesis, unravelling mechanisms of stemness
      maintenance, cell differentiation, and cell-to-cell interactions. The
      transplantation of SSCs can contribute to the preservation of the genome of
      valuable individuals in assisted reproduction programs. In addition to the
      importance of SSCs for male fertility, their study has recently stimulated
      interest in the generation of genetically modified animals because manipulations
      of the male germ line at the SSC stage will be maintained in the long term and
      transmitted to the offspring. Studies performed mainly in the mouse model have
      laid the groundwork for facilitating advancements in the field of male germ line
      biology, but more progress is needed in nonrodent species in order to translate
      the technology to the agricultural and biomedical fields. The lack of reliable
      markers for isolating germ cells from testicular somatic cells and the lack of
      knowledge of the requirements for germ cell maintenance have precluded their long
      term maintenance in domestic animals. Nevertheless, some progress has been made.
      In this review, we will focus on the state of the art in the isolation,
      characterization, culture, and manipulation of SSCs and the use of germ cell
      transplantation in domestic animals. 

PMID- 25991704
TI  - Porcine models of cutaneous wound healing.
AB  - Cutaneous wound healing in the pig is frequently used as a model for human
      cutaneous wound healing. In this review, we examine the appropriateness of this
      model for studying normal and pathological wound healing, and describe models for
      chronic nonhealing wounds, diabetic wounds, burns, and hypertrophic scars. In
      addition, we focus on studies that have used pigs to evaluate wound-healing
      therapies, and discuss genetic engineering technology in the pig that may advance
      our knowledge of wound healing. We conclude that, although not perfect, the pig
      offers a versatile model that can be adjusted to mimic a wide range of clinical
      scenarios. 

PMID- 25991705
TI  - IACUC Considerations for the Use of Livestock in Translational Research.
AB  - Through its program oversight function, the institutional animal care and use
      committee (IACUC) plays a central role in ensuring the humane use and care of
      animals in research. To be effective in this role, the IACUC requires explicit
      knowledge of the species for which it bears oversight responsibility. Owing to a
      variety of species-specific factors, such as their relatively large size and
      range of acceptable housing environments, livestock present many special
      considerations for the IACUC. This article reviews many of those considerations
      in a format intended to aid IACUCs in the review of animal care and use programs
      involving livestock species used in translational research. 

PMID- 25991706
TI  - A screen of maternally inherited microbial endosymbionts in oribatid mites
      (Acari: Oribatida).
AB  - We determined the distribution of microbial endosymbionts as possible agents of
      parthenogenesis in Oribatida. We screened mites from 20 species of 14 families
      suspected to be parthenogenetic from the absence or rarity of males. Our research
      included parthenogenesis-inducing bacteria Wolbachia spp., Cardinium spp.,
      Rickettsia spp., and additionally Arsenophonus, Spiroplasma and microsporidia
      that can also manipulate host reproduction. We detected the endosymbionts by PCR
      based methods and transmission electron microscopy (TEM) observation of fixed and
      stained preparations of host cells. We detected Wolbachia only in one Oribatida
      species, Oppiella nova, by identifying Wolbachia genes using PCR. TEM
      observations confirmed infection by the endosymbiont in O. nova and its lack in
      other Oribatida species. Sequence analysis of hcpA and fbpA genes showed that the
      Wolbachia strain from O. nova was different from strains characterized in some
      insects, crustaceans (Isopoda), mites (Tetranychidae), springtails (Hexapoda) and
      roundworms (Nematoda). The analysis strongly suggested that the Wolbachia sp.
      strain found in O. nova did not belong to supergroups A, B, C, D, E, F, H or M.
      We found that the sequences of Wolbachia from O. nova were clearly distantly
      related to sequences from the bacteria of the other supergroups. This observation
      makes O. nova a unique Wolbachia host in terms of the distinction of the strain.
      The role of these micro-organisms in O. nova remains unknown and is an issue to
      investigate. 

PMID- 25991707
TI  - On the stability of a spherical tumour.
AB  - The mathematical analysis of the tumour growth attracted a lot of interest in the
      last two decades. However, as of today no generally accepted model for tumour
      growth exists. This is due partially to the incomplete understanding of the
      related pathology as well as the extremely complicated procedure that guides the
      evolution of a tumour. In the present work, we analyse the stability of a
      spherical tumour for four continuous models of an avascular tumour. Conditions
      for the stability are stated and the results are implemented numerically. It is
      observed that the steady-state radii that secure the stability of the tumour are
      different for each of the four models, although the differences are not very
      pronounced.

PMID- 25991708
TI  - Physiological genomics--what is in a name?

PMID- 25991703
TI  - Porcine models of muscular dystrophy.
AB  - Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a
      failure to accumulate the cytoskeletal protein dystrophin. This disease has been
      studied using a variety of animal models including fish, mice, rats, and dogs.
      While these models have contributed substantially to our mechanistic
      understanding of the disease and disease progression, limitations inherent to
      each model have slowed the clinical advancement of therapies, which necessitates
      the development of novel large-animal models. Several porcine dystrophin
      deficient models have been identified, although disease severity may be so severe
      as to limit their potential contributions to the field. We have recently
      identified and completed the initial characterization of a natural porcine model
      of dystrophin insufficiency. Muscles from these animals display characteristic
      focal necrosis concomitant with decreased abundance and localization of
      dystrophin-glycoprotein complex components. These pigs recapitulate many of the
      cardinal features of muscular dystrophy, have elevated serum creatine kinase
      activity, and preliminarily appear to display altered locomotion. They also
      suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy
      models could allow refinement of dosing strategies in human-sized animals in
      preparation for clinical trials. From an animal handling perspective, these pigs
      can generally be treated normally, with the understanding that acute stress can
      lead to sudden death. In summary, the ability to create genetically modified pig
      models and the serendipitous discovery of genetic disease in the swine industry
      has resulted in the emergence of new animal tools to facilitate the critical
      objective of improving the quality and length of life for boys afflicted with
      such a devastating disease. 

PMID- 25991710
TI  - Prevention and treatment of decompression sickness using training and in-water
      recompression among fisherman divers in Vietnam.
AB  - INTRODUCTION: Many fisherman divers in Vietnam suffer from decompression sickness
      (DCS) causing joint pain, severe neurological deficit or even death. The
      objective of this pilot study was to evaluate the effectiveness of a training
      programme to prevent DCS and also treat DCS using the method of in-water
      recompression (IWR). METHODS: 63 divers were interviewed and trained over a
      period of 3 years from 2009. Fifty one per cent of all trained divers were
      reinterviewed in 2011-2012 to collect mortality and morbidity data as well as
      information on changes in diving practices. RESULTS: Since 2009, most fisherman
      divers have changed their practices by reducing bottom time or depth. Mortality
      was reduced and the incidence of severe neurological DCS decreased by 75%. Twenty
      four cases of DCS were treated by IWR. Ten cases of joint pain were treated with
      IWR using air, affording immediate relief in all cases. Out of 10 cases of
      neurological DCS, 4/4 recovered completely after IWR with oxygen whereas only 2/6
      subjects recovered immediately after IWR with air. In addition, 3/4 further cases
      of DCS treated with IWR using oxygen immediately recovered. CONCLUSIONS: Our
      results suggest that IWR is effective for severe neurological DCS in remote
      fishing communities, especially with oxygen.

PMID- 25991709
TI  - Identification of candidate genes that underlie the QTL on chromosome 1 that
      mediates genetic differences in stress-ethanol interactions.
AB  - Alcoholism, stress, and anxiety are strongly interacting heritable, polygenetic
      traits. In a previous study, we identified a quantitative trait locus (QTL) on
      murine chromosome (Chr) 1 between 23.0 and 31.5 Mb that modulates genetic
      differences in the effects of ethanol on anxiety-related phenotypes. The goal of
      the present study was to extend the analysis of this locus with a focus on
      identifying candidate genes using newly available data and tools. Anxiety-like
      behavior was evaluated with an elevated zero maze following saline or ethanol
      injections (1.8 g/kg) in C57BL/6J, DBA2J, and 72 BXD strains. We detected
      significant effects of strain and treatment and their interaction on anxiety
      related behaviors, although surprisingly, sex was not a significant factor. The
      Chr1 QTL is specific to the ethanol-treated cohort. Candidate genes in this locus
      were evaluated using now standard bioinformatic criteria. Collagen 19a1 (Col19a1)
      and family sequence 135a (Fam135a) met most criteria but have lower expression
      levels and lacked biological verification and, therefore, were considered less
      likely candidates. In contrast, two other genes, the prenylated protein tyrosine
      phosphate family member Ptp4a1 (protein tyrosine phosphate 4a1) and the zinc
      finger protein Phf3 (plant homeoDomain finger protein 3) met each of our
      bioinformatic criteria and are thus strong candidates. These findings are also of
      translational relevance because both Ptp4a1 and Phf3 have been nominated as
      candidates genes for alcohol dependence in a human genome-wide association study.
      Our findings support the hypothesis that variants in one or both of these genes
      modulate heritable differences in the effects of ethanol on anxiety-related
      behaviors. 

PMID- 25991712
TI  - In vitro degradation and cell viability assessment of Zn-3Mg alloy for
      biodegradable bone implants.
AB  - This article reports the in vitro degradation and cytotoxicity assessment of Zn
      3Mg alloy developed for biodegradable bone implants. The alloy was prepared using
      casting, and its microstructure was composed of Mg2Zn11 intermetallic phase
      distributed within a Zn-rich matrix. The degradation assessment was done using
      potentiodynamic polarization and electrochemical impedance spectrometry. The cell
      viability and the function of normal human osteoblast cells were assessed using 3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium and alkaline phosphatase extracellular enzyme activity assays. The
      results showed that the degradation rate of the alloy was slower than those of
      pure Zn and pure Mg due to the formation of a high polarization resistance oxide
      film. The alloy was cytocompatible with the normal human osteoblast cells at low
      concentrations (<0.5 mg/mL), and its alkaline phosphatase activity was superior
      to pure Mg. This assessment suggests that Zn-3Mg alloy has the potential to be
      developed as a material for biodegradable bone implants, but the toxicity limit
      must be carefully observed. 

PMID- 25991711
TI  - Data Resource Profile: Accessible Resource for Integrated Epigenomic Studies
      (ARIES).

PMID- 25991713
TI  - Necromechanics: Death-induced changes in the mechanical properties of human
      tissues.
AB  - After the death phenomenon, the rigor mortis development, characterized by body
      stiffening, is one of the most evident changes that occur in the body. In this
      work, the development of rigor mortis was assessed using a skinfold caliper in
      human cadavers and in live people to measure the deformation in the biceps
      brachii muscle in response to the force applied by the device. Additionally, to
      simulate the measurements with the finite element method, a two-dimensional model
      of an arm section was used. As a result of the experimental procedure, a decrease
      in deformation with increasing postmortem time was observed, which corresponds to
      an increase in rigidity. As expected, the deformations for the live subjects were
      higher. The finite element method analysis showed a correlation between the c1
      parameter of the neo-Hookean model in the 4- to 8-h postmortem interval. This was
      accomplished by adjusting the c1 material parameter in order to simulate the
      measured experimental displacement. Despite being a preliminary study, the
      obtained results show that combining the proposed experimental procedure with a
      numerical technique can be very useful in the study of the postmortem mechanical
      modifications of human tissues. Moreover, the use of data from living subjects
      allows us to estimate the time of death paving the way to establish this process
      as an alternative to the existing techniques. This solution constitutes a
      portable, non-invasive method of estimating the postmortem interval with direct
      quantitative measurements using a skinfold caliper. The tools and methods
      described can be used to investigate the subject and to gain epidemiologic
      knowledge on rigor mortis phenomenon. 

PMID- 25991714
TI  - Virtual prototyping of a semi-active transfemoral prosthetic leg.
AB  - This article presents a virtual prototyping study of a semi-active lower limb
      prosthesis to improve the functionality of an amputee during prosthesis
      environment interaction for level ground walking. Articulated ankle-foot
      prosthesis and a single-axis semi-active prosthetic knee with active and passive
      operating modes were considered. Data for level ground walking were collected
      using a photogrammetric method in order to develop a base-line simulation model
      and with the hip kinematics input to verify the proposed design. The simulated
      results show that the semi-active lower limb prosthesis is able to move
      efficiently in passive mode, and the activation time of the knee actuator can be
      reduced by approximately 50%. Therefore, this semi-active system has the
      potential to reduce the energy consumption of the actuators required during level
      ground walking and requires less compensation from the amputee due to lower
      deviation of the vertical excursion of body centre of mass. 

PMID- 25991716
TI  - A new alternative to expandable pedicle screws: Expandable poly-ether-ether
      ketone shell.
AB  - Screw pullout is a very common problem in the fixation of sacrum with pedicle
      screws. The principal cause of this problem is that the cyclic micro motions in
      the fixation of sacrum are higher than the other regions of the vertebrae that
      limit the osteo-integration between bone and screw. In addition to that, the bone
      quality is very poor at sacrum region. This study investigated a possible
      solution to the pullout problem without the expandable screws' handicaps. Newly
      designed poly-ether-ether-ketone expandable shell and classical pedicle screws
      were biomechanically compared. Torsion test, pullout tests, fatigue tests,
      flexion/extension moment test, axial gripping capacity tests and torsional
      gripping capacity tests were conducted in accordance with ASTM F543, F1798 and
      F1717. Standard polyurethane foam and calf vertebrae were used as embedding
      medium for pullout tests. Classical pedicle screw pullout load on polyurethane
      foam was 564.8 N compared to the failure load for calf vertebrae's 1264 N. Under
      the same test conditions, expandable poly-ether-ether-ketone shell system's
      pullout loads from polyurethane foam and calf vertebrae were 1196.3 and 1890 N,
      respectively. The pullout values for expandable poly-ether-ether-ketone shell
      were 33% and 53% higher than classical pedicle screw on polyurethane foam and
      calf vertebrae, respectively. The expandable poly-ether-ether-ketone shell
      exhibited endurance on its 90% of yield load. Contrary to poly-ether-ether-ketone
      shell, classical pedicle screw exhibited endurance on 70% of its yield load.
      Expandable poly-ether-ether-ketone shell exhibited much higher pullout
      performance than classical pedicle screw. Fatigue performance of expandable poly
      ether-ether-ketone shell is also higher than classical pedicle screw due to
      damping the micro motion capacity of the poly-ether-ether-ketone. Expandable poly
      ether-ether-ketone shell is a safe alternative to all other expandable pedicle
      screw systems on mechanical perspective. 

PMID- 25991715
TI  - In vitro wear testing of the PyroCarbon proximal interphalangeal joint
      replacement: Five million cycles of flexion and extension.
AB  - Clinical results of the PyroCarbon proximal interphalangeal joint replacement are
      inconsistent with various complications reported. To address this, in vitro
      testing was conducted using finger joint simulators. Two PyroCarbon proximal
      interphalangeal prostheses were tested in a lubricant of dilute bovine serum to 5
      * 10(6) cycles of flexion-extension (90 degrees -30 degrees ) with dynamic forces
      of 10 N applied. At intervals of 3000 cycles testing ceased and a static load of
      100 N was applied to simulate gripping. In addition, two 'control' prostheses
      were immersed alongside the test prostheses to account for lubricant absorption.
      Wear and roughness averages (Ra) were measured every 1 * 10(6) cycles. Minimal
      wear for all of the components was measured with a negligible increase in Ra for
      most of the components. One condyle of one component increased in Ra over the 5 *
      10(6) cycles with a value above the recommended 50 nm. Unidirectional marks were
      visible on the condyle from micrographs, consistent with an abrasive wear mode. 

PMID- 25991717
TI  - Numerical modelling of crural fascia mechanical interaction with muscular
      compartments.
AB  - The interaction of the crural fascia with muscular compartments and surrounding
      tissues can be at the origin of different pathologies, such as compartment
      syndrome. This pathology consists in the onset of excessive intracompartmental
      pressure, which can have serious consequences for the patient, compromising blood
      circulation. The investigation of compartment syndrome etiology also takes into
      account the alteration of crural fascia mechanical properties as a cause of the
      syndrome, where the fascial stiffening would result in the rise of
      intracompartmental pressure. This work presents a computational approach toward
      evaluating some biomechanical aspects of the problem, within the context of a
      more global viewpoint. Finite element analyses of the interaction phenomena of
      the crural fascia with adjacent regions are reported here. This study includes
      the effects of a fascial stiffness increase along the proximal-distal direction
      and their possible clinical implications. Furthermore, the relationship between
      different pre-strain levels of the crural fascia in the proximal-distal direction
      and the rise of internal pressure in muscular compartments are considered. The
      numerical analyses can clarify which aspects could be directly implied in the
      rise of compartment syndrome, leading to greater insight into muscle-fascia
      mechanical phenomena, as well as promoting experimental investigation and
      clinical analysis of the syndrome. 

PMID- 25991718
TI  - A novel four-caster manual vehicle manoeuvring investigation: Higher loading
      weights require larger turning spaces.
AB  - Patient-hoists, goods-trolleys and other omni-directional manually operated
      vehicles are ubiquitous. Yet no substantive, empirically based dynamic analysis
      has been made of these four-caster vehicles despite manual handling concerns. A
      relationship between loading-weight and turning space is indicated by theoretical
      analysis which further shows that this effect is represented by only 11 different
      manoeuvres. A qualitative account of the theory is presented. These 11 manoeuvres
      were implemented experimentally. A total of 17 subjects selected a maximum
      comfortable loading-weight for the four-caster vehicle for each of the 11
      manoeuvres. Vehicle displacement and handle forces were measured for different
      centres of zero velocity. The median loading-weight of the manoeuvre with the
      highest loading-weight selections was 101% greater than the mean loading-weight
      of the three manoeuvres with the lowest loading-weight selections. The manoeuvre
      with the highest loading-weight selections required a larger vehicle turning
      space: one dimension increased by 37% (173 mm) compared with the three lowest
      loading-weight selection manoeuvres and the other dimension increased by 17% (130
      mm) compared with one of the lowest loading-weight selection manoeuvres. Higher
      loading-weights require larger turning spaces. These results can contribute to
      building designs which facilitate safe manual manoeuvring of four-caster
      vehicles. 

PMID- 25991719
TI  - Enhanced expression of epithelial sodium channels causes salt-induced
      hypertension in mice through inhibition of the alpha2-isoform of Na+, K+-ATPase.
AB  - Knockout of the Nedd4-2 gene in mice results in overexpression of epithelial
      sodium channels (ENaC) on the plasma membrane in the kidney, choroid plexus and
      brain nuclei. These mice exhibit enhanced pressor responses to CSF [Na(+)] as
      well as dietary salt-induced hypertension which both can be blocked by central
      infusion of the ENaC blocker benzamil. Functional studies suggest that ENaC
      activation in the CNS results in release of endogenous ouabain (EO) and
      inhibition of the alpha2-isoform of Na(+), K(+)-ATPase. To test this concept more
      specifically, we studied Nedd4-2(-/-) mice expressing the ouabain-resistant
      alpha2R/R-isoform of Na(+), K(+)-ATPase. Intracerebroventricular (icv) infusion
      of Na(+)-rich aCSF (225 mmol/L Na(+) at 0.4 MUL/min) increased MAP by 10-15 mmHg
      in wild-type mice and by 25-30 mmHg in Nedd4-2(-/-) mice, but by only ~5 mmHg in
      alpha2R/R and in alpha2R/R/Nedd4-2(-/-) mice. Icv infusion of EO-binding Fab
      fragments also blocked the BP response in Nedd4-2(-/-) mice. In Nedd4-2(-/-)
      mice, 8% high-salt diet increased MAP by 25-30 mmHg, but in alpha2R/R/Nedd4-2(-/
      ) mice, it increased by only 5-10 mmHg. In contrast, Nedd4-2(-/-) or alpha2R/R
      did not affect the hypertension caused by sc infusion of Ang II. These findings
      substantiate the concept that enhanced ENaC activity causes salt-induced pressor
      responses mainly through EO inhibiting the alpha2-isoform of Na(+), K(+)-ATPase
      in the brain. 

PMID- 25991720
TI  - Effects of ambient temperature on glucose tolerance and insulin sensitivity test
      outcomes in normal and obese C57 male mice.
AB  - Mice are commonly used as animal models to study human metabolic diseases, but
      experiments are typically performed at room temperature, which is far below their
      thermoneutral zone and is associated with elevated heart rate, food intake, and
      energy expenditure. We set out to study how ambient temperature affects glucose
      tolerance and insulin sensitivity in control and obese male mice. Adult male
      C57BL/6J mice were housed at room temperature (23 degrees C) for 6 weeks and fed
      either control or high fat diet. They were then fasted for 6 h before glucose or
      insulin tolerance tests were performed at 15, 20, 25, or 30 degrees C. To ensure
      that behavioral thermoregulation did not counterbalance the afflicted ambient
      temperatures, oxygen consumption was determined on mice with the same
      thermoregulatory opportunities as during the tests. Decreasing ambient
      temperatures increased oxygen consumption and body mass loss during fasting in
      both groups. Mice fed high fat diet had improved glucose tolerance at 30 degrees
      C and increased levels of fasting insulin followed by successive decrease of
      fasting glucose. However, differences between control and high-fat diet mice were
      present at all temperatures. Ambient temperature did not affect glucose tolerance
      in control group and insulin tolerance in either of the groups. Ambient
      temperature affects glucose metabolism in mice and this effect is phenotype
      specific. 

PMID- 25991722
TI  - Nontubular epithelial Na+ channel proteins in cardiovascular regulation.

PMID- 25991721
TI  - Maternal high fat and/or salt consumption induces sex-specific inflammatory and
      nutrient transport in the rat placenta.
AB  - Maternal high fat and salt consumption are associated with developmental
      programming of disease in adult offspring. Inadequacies in placental nutrient
      transport may explain these 'programmed effects'. Diet-induced inflammation may
      have detrimental effects on placental function leading to alteration of key
      nutrient transporters. We examined the effects of maternal high fat and/or salt
      diets on markers of placental nutrient transport and inflammation. Sprague-Dawley
      rats were assigned to (1) control (CD; 1% Salt 10% kcal from fat); (2) high salt
      (SD; 4% salt, 10% kcal from fat); (3) high fat (HF; 1% Salt 45% kcal from fat) or
      (4) high fat high salt (HFSD; 4% salt, 45% kcal from fat) 21 days prior to and
      throughout gestation. At embryonic day 18, dams were killed by isoflurane
      anesthesia followed by decapitation; placenta/fetuses were weighed, sexed, and
      collected for molecular analysis. Maternal SD, HF, and HFSD consumption decreased
      weight of placenta derived from male offspring; however, weight of placenta
      derived from female offspring was only reduced with maternal HF diet. This was
      associated with increased expression of LPL, SNAT2, GLUT1, and GLUT4 in placenta
      derived from male offspring suggesting increased fetal exposure to free fatty
      acids and glucose. Maternal SD, HF, and HFSD diet consumption increased
      expression of proinflammatory mediators IL-1beta, TNFalpha, and CD68 in male
      placenta. Our results suggest that a proinflammatory placental profile results in
      detrimental alterations in nutrient transport which may contribute to the
      developmental origins of cardio-metabolic disturbances in offspring throughout
      life. 

PMID- 25991723
TI  - Moderate-intensity treadmill exercise training decreases murine cardiomyocyte
      cross-sectional area.
AB  - The aim of this study was to examine the impact of moderate-intensity treadmill
      exercise on the structure and function of the murine heart and its associated
      impact on Akt-AMPK-mTOR signaling. A secondary aim was to test whether the
      exercise phenotype was altered following a cardiotoxic bolus dose of doxorubicin
      (DOX). Two-month-old C57Bl/6J female mice remained sedentary (SED, n = 12) or
      were progressively trained with treadmill running for 2 months up to 18 m/min; 60
      min/day, 5 days/weeks (EX, n = 11) or EX + DOX (15 mg/kg/dose) (EX + DOX, n = 6).
      Following treadmill training, mice underwent graded exercise tolerance testing
      and echocardiography. Training improved graded exercise tolerance by 68 +/- 5%
      relative to SED, and this effect was not altered with bolus DOX. There were no
      changes in relative heart size with EX or EX + DOX versus SED. Regional posterior
      wall thickening was improved in EX and abrogated in EX + DOX. EX had a reduced
      cardiomyocyte cross-sectional area (CSA) relative to SED, and CSA was further
      attenuated with DOX. Following EX, AMPK-associated phosphorylation of
      ULK1(ser317) tended to be lower relative to SED. Akt-associated phosphorylation
      of TSC2(thr1462) and mTOR(ser2448) were also decreased relative to SED. We
      observed an increase in AMPK activity with DOX that was not translated to
      downstream AMPK phosphorylation sites. We conclude that 2 months of moderate
      treadmill exercise training improves regional cardiac function and exercise
      capacity, but does not induce relative physiologic hypertrophy in female mice.
      Differential responses in Akt-AMPK-mTOR signaling may mediate the observed
      phenotype. 

PMID- 25991724
TI  - ATP-dependent Conformational Changes Trigger Substrate Capture and Release by an
      ECF-type Biotin Transporter.
AB  - Energy-coupling factor (ECF) transporters for vitamins and metal ions in
      prokaryotes consist of two ATP-binding cassette-type ATPases, a substrate
      specific transmembrane protein (S component) and a transmembrane protein (T
      component) that physically interacts with the ATPases and the S component. The
      mechanism of ECF transporters was analyzed upon reconstitution of a bacterial
      biotin transporter into phospholipid bilayer nanodiscs. ATPase activity was not
      stimulated by biotin and was only moderately reduced by vanadate. A non
      hydrolyzable ATP analog was a competitive inhibitor. As evidenced by cross
      linking of monocysteine variants and by site-specific spin labeling of the Q
      helix followed by EPR-based interspin distance analyses, closure and reopening of
      the ATPase dimer (BioM2) was a consequence of ATP binding and hydrolysis,
      respectively. A previously suggested role of a stretch of small hydrophobic amino
      acid residues within the first transmembrane segment of the S units for S unit/T
      unit interactions was structurally and functionally confirmed for the biotin
      transporter. Cross-linking of this segment in BioY (S) using homobifunctional
      thiol-reactive reagents to a coupling helix of BioN (T) indicated a reorientation
      rather than a disruption of the BioY/BioN interface during catalysis.
      Fluorescence emission of BioY labeled with an environmentally sensitive
      fluorophore was compatible with an ATP-induced reorientation and consistent with
      a hypothesized toppling mechanism. As demonstrated by [(3)H]biotin capture
      assays, ATP binding stimulated substrate capture by the transporter, and
      subsequent ATP hydrolysis led to substrate release. Our study represents the
      first experimental insight into the individual steps during the catalytic cycle
      of an ECF transporter in a lipid environment. 

PMID- 25991725
TI  - Anopheles Midgut FREP1 Mediates Plasmodium Invasion.
AB  - Malaria transmission depends on sexual stage Plasmodium parasites successfully
      invading Anopheline mosquito midguts following a blood meal. However, the
      molecular mechanisms of Plasmodium invasion of mosquito midguts have not been
      fully elucidated. Previously, we showed that genetic polymorphisms in the
      fibrinogen-related protein 1 (FREP1) gene are significantly associated with
      Plasmodium falciparum infection in Anopheles gambiae, and FREP1 is important for
      Plasmodium berghei infection of mosquitoes. Here we identify that the FREP1
      protein is secreted from the mosquito midgut epithelium and integrated as
      tetramers into the peritrophic matrix, a chitinous matrix formed inside the
      midgut lumen after a blood meal feeding. Moreover, we show that the FREP1 can
      directly bind Plasmodia sexual stage gametocytes and ookinetes. Notably, ablating
      FREP1 expression or targeting FREP1 with antibodies significantly decreases P.
      falciparum infection in mosquito midguts. Our data support that the mosquito
      expressed FREP1 mediates mosquito midgut invasion by multiple species of
      Plasmodium parasites via anchoring ookinetes to the peritrophic matrix and
      enabling parasites to penetrate the peritrophic matrix and the epithelium. Thus,
      targeting FREP1 can limit malaria transmission. 

PMID- 25991728
TI  - Effect of palliative care nurse champions on the quality of dying in the hospital
      according to bereaved relatives: A controlled before-and-after study.
AB  - BACKGROUND: To improve the quality of end-of-life care, hospitals increasingly
      appoint palliative care nurse champions. AIM: We investigated the effect of nurse
      champions on the quality of life during the last 3 days of life and the quality
      of dying as experienced by bereaved relatives. DESIGN: A controlled before-and
      after study (June 2009-July 2012). Halfway, in each of seven intervention wards,
      two nurse champions were appointed; 11 wards served as control wards. The quality
      of life during the last 3 days of life, quality of dying and multiple dimensions
      of quality of dying were compared before and after the introduction of nurse
      champions. SETTING: In a university hospital, each death at non-intensive care
      units was followed up by an invitation to relatives (10-13 weeks later) to answer
      a questionnaire. RESULTS: For the two periods, data were collected on 86 and 84
      patients in intervention wards and on 108 and 118 patients in control wards
      (overall response: 52%). In the intervention wards, no differences were found in
      the quality of life during the last 3 days of life and the quality of dying
      scores: in both periods, median score for the quality of life during the last 3
      days of life was 3.0 and for the quality of dying 7.0. No differences were found
      in multiple quality of dying dimensions. In control wards, the median quality of
      dying score was 7.0 pre-intervention and 6.0 post-intervention (p = 0.04). Other
      scores were comparable with those in intervention wards. CONCLUSION: Performing a
      complex intervention study in palliative care proved to be feasible. This study
      showed no differences in the experiences of bereaved relatives after introduction
      of nurse champions. The complexity of palliative care in the hospital might
      require more intensive and longer training of nurse champions.

PMID- 25991726
TI  - Defective Guanine Nucleotide Exchange in the Elongation Factor-like 1 (EFL1)
      GTPase by Mutations in the Shwachman-Diamond Syndrome Protein.
AB  - Ribosome biogenesis is orchestrated by the action of several accessory factors
      that provide time and directionality to the process. One such accessory factor is
      the GTPase EFL1 involved in the cytoplasmic maturation of the ribosomal 60S
      subunit. EFL1 and SBDS, the protein mutated in the Shwachman-Diamond syndrome
      (SBDS), release the anti-association factor eIF6 from the surface of the
      ribosomal subunit 60S. Here we report a kinetic analysis of fluorescent guanine
      nucleotides binding to EFL1 alone and in the presence of SBDS using fluorescence
      stopped-flow spectroscopy. Binding kinetics of EFL1 to both GDP and GTP suggests
      a two-step mechanism with an initial binding event followed by a conformational
      change of the complex. Furthermore, the same behavior was observed in the
      presence of the SBDS protein irrespective of the guanine nucleotide evaluated.
      The affinity of EFL1 for GTP is 10-fold lower than that calculated for GDP.
      Association of EFL1 to SBDS did not modify the affinity for GTP but dramatically
      decreased that for GDP by increasing the dissociation rate of the nucleotide.
      Thus, SBDS acts as a guanine nucleotide exchange factor (GEF) for EFL1 promoting
      its activation by the release of GDP. Finally, fluorescence anisotropy
      measurements showed that the S143L mutation present in the Shwachman-Diamond
      syndrome altered a surface epitope for EFL1 and largely decreased the affinity
      for it. These results suggest that loss of interaction between these proteins due
      to mutations in the disease consequently prevents the nucleotide exchange
      regulation the SBDS exerts on EFL1. 

PMID- 25991727
TI  - Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality.
AB  - The bipolar kinesin-5 motors are one of the major players that govern mitotic
      spindle dynamics. Their bipolar structure enables them to cross-link and slide
      apart antiparallel microtubules (MTs) emanating from the opposing spindle poles.
      The budding yeast kinesin-5 Cin8 was shown to switch from fast minus-end- to slow
      plus-end-directed motility upon binding between antiparallel MTs. This unexpected
      finding revealed a new dimension of cellular control of transport, the mechanism
      of which is unknown. Here we have examined the role of the C-terminal tail domain
      of Cin8 in regulating directionality. We first constructed a stable dimeric
      Cin8/kinesin-1 chimera (Cin8Kin), consisting of head and neck linker of Cin8
      fused to the stalk of kinesin-1. As a single dimeric motor, Cin8Kin switched
      frequently between plus and minus directionality along single MTs, demonstrating
      that the Cin8 head domains are inherently bidirectional, but control over
      directionality was lost. We next examined the activity of a tetrameric Cin8
      lacking only the tail domains (Cin8Deltatail). In contrast to wild-type Cin8, the
      motility of single molecules of Cin8Deltatail in high ionic strength was slow and
      bidirectional, with almost no directionality switches. Cin8Deltatail showed only
      a weak ability to cross-link MTs in vitro. In vivo, Cin8Deltatail exhibited bias
      toward the plus-end of the MTs and was unable to support viability of cells as
      the sole kinesin-5 motor. We conclude that the tail of Cin8 is not necessary for
      bidirectional processive motion, but is controlling the switch between plus- and
      minus-end-directed motility. 

PMID- 25991729
TI  - The changing demographics of inpatient hospice death: Population-based cross
      sectional study in England, 1993-2012.
AB  - BACKGROUND: Studies in the United Kingdom and elsewhere have suggested inequality
      of hospice provision with respect to factors such as age, diagnosis and socio
      economic position. How this has changed over time is unknown. AIM: To describe
      the factors associated with inpatient hospice death in England and examine how
      these have changed over time. DESIGN: Population-based study. Multivariable
      Poisson regression compared 1998-2002, 2003-2007 and 2008-2012, with 1993-1997.
      Explanatory variables included individual factors (age, gender, marital status,
      underlying cause of death) and area-based measures of deprivation. SETTING:
      Adults aged 25 years and over who died in inpatient hospice units in England
      between 1993 and 2002 (n = 446,615). RESULTS: The annual number of hospice deaths
      increased from 17,440 in 1993 to 26,032 in 2012, accounting for 3.4% of all
      deaths in 1993 and 6.0% in 2012. A total of 50.6% of hospice decedents were men;
      the mean age was 69.9 (standard deviation: 12.4) years. The likelihood of hospice
      decedents being in the oldest age group (>85 years) increased over time
      (proportion ratio: 1.43, 95% confidence interval: 1.39 to 1.48 for 2008-2012
      compared to 1993-1997). Just 5.2% of all hospice decedents had non-cancer
      diagnoses, though the likelihood of non-cancer conditions increased over time
      (proportion ratio: 1.41, 95% confidence interval: 1.37 to 1.46 for 2008-2012
      compared to 1993-1997). The likelihood of hospice decedents being resident in the
      least deprived quintile increased over time (proportion ratio: 1.25, 95%
      confidence interval: 1.22 to 1.29 for 2008-2012 compared to 1993-1997).
      CONCLUSION: The increase in non-cancer conditions among hospice decedents is
      encouraging although absolute numbers remain very small. Deprivation trends are
      concerning and require further exploration.

PMID- 25991730
TI  - Multi-segment kinematic model to assess three-dimensional movement of the spine
      and back during gait.
AB  - BACKGROUND: Relatively little is known about spine during gait compared to
      movement analysis of the lower extremities. The trunk is often regarded and
      analysed as a single rigid segment and there is a paucity of information on inter
      segmental movement within the spine and its relationship to pelvis and lower
      limbs. OBJECTIVES: To develop and validate a new multi-segment kinematic model to
      assess regional three-dimensional movement of the lumbar, lower thoracic and
      upper thoracic spine during gait. STUDY DESIGN: Observational study. METHODS: The
      study was conducted in two parts: (1) to provide validation measures on the
      kinematic model built in commercially available software and (2) to apply the
      marker configuration to the spine at T3, T8 and L3 during gait analysis on 10
      healthy male volunteers. RESULTS: Proposed model revealed excellent concurrent
      validation measures between an applied input angle to the recorded output angle
      from the kinematic model. A high reliability was observed during gait analysis,
      both during a single session and between sessions for all participants.
      CONCLUSION: The thoracic region of the spine should not be modelled as a single
      rigid segment and the proposed three-dimensional cluster is reliable and
      repeatable to assess the inter-segmental movement of the spine. CLINICAL
      RELEVANCE: Reliable kinematic data can be collected using the three-dimensional
      cluster technique, thus, allowing researchers to accurately distinguish between
      movement patterns of healthy individuals to those with a clinical condition, and
      provide confidence in data acquisition during the monitoring process of an
      implemented rehabilitation intervention programme.

PMID- 25991731
TI  - EDAC: Epithelial defence against cancer-cell competition between normal and
      transformed epithelial cells in mammals.
AB  - During embryonic development or under certain pathological conditions, viable but
      suboptimal cells are often eliminated from the cellular society through a process
      termed cell competition. Cell competition was originally identified in Drosophila
      where cells with different properties compete for survival; 'loser' cells are
      eliminated from tissues and consequently 'winner' cells become dominant. Recent
      studies have shown that cell competition also occurs in mammals. While apoptotic
      cell death is the major fate for losers in Drosophila, outcompeted cells show
      more variable phenotypes in mammals, such as cell death-independent apical
      extrusion and cellular senescence. Molecular mechanisms underlying these
      processes have been recently revealed. Especially, in epithelial tissues, normal
      cells sense and actively eliminate the neighbouring transformed cells via
      cytoskeletal proteins by the process named epithelial defence against cancer
      (EDAC). Here, we introduce this newly emerging research field: cell competition
      in mammals. 

PMID- 25991733
TI  - Correction.

PMID- 25991732
TI  - The Arabidopsis SWI2/SNF2 Chromatin Remodeling ATPase BRAHMA Targets Directly to
      PINs and Is Required for Root Stem Cell Niche Maintenance.
AB  - BRAHMA (BRM), a SWI/SNF chromatin remodeling ATPase, is essential for the
      transcriptional reprogramming associated with development and cell
      differentiation in Arabidopsis thaliana. In this study, we show that loss-of
      function mutations in BRM led to defective maintenance of the root stem cell
      niche, decreased meristematic activity, and stunted root growth. Mutations of BRM
      affected auxin distribution by reducing local expression of several PIN-FORMED
      (PIN) genes in the stem cells and impaired the expression of the stem cell
      transcription factor genes PLETHORA (PLT1) and PLT2. Chromatin
      immunoprecipitation assays showed that BRM could directly target to the chromatin
      of PIN1, PIN2, PIN3, PIN4, and PIN7. In addition, genetic interaction assays
      indicate that PLTs acted downstream of BRM, and overexpression of PLT2 partially
      rescued the stem cell niche defect of brm mutants. Taken together, these results
      support the idea that BRM acts in the PLT pathway to maintain the root stem cell
      niche by altering the expression of PINs. 

PMID- 25991735
TI  - Social Support and Sexual Risk Among Establishment-Based Female Sex Workers in
      Tijuana.
AB  - Social support can affect health outcomes of female sex workers. In this
      inductive feminist grounded theory study based on 20 in-depth interviews, we
      explore how establishment-based female sex workers in Tijuana perceive the impact
      of the connections among women on their lives and health. Participants elected to
      discuss the importance of social support from mothers, sisters, friends, and co
      workers, and the empowering and disempowering aspects of these relationships. In
      previous studies, scholars demonstrated the efficacy of formal organization of
      female sex workers in promoting the mitigation of sexual and HIV risk. We show
      the importance of informal ties with other women. Some participants mentioned
      competitive relationships, others talked about cooperation and the desire for a
      venue to learn from one another. Social interactions with other women are
      especially empowering when female sex workers can openly engage in "woman talk"
      that may contribute to the mitigation of sexual and HIV risk. 

PMID- 25991734
TI  - Wheat Stripe Rust Resistance Protein WKS1 Reduces the Ability of the Thylakoid
      Associated Ascorbate Peroxidase to Detoxify Reactive Oxygen Species.
AB  - Stripe rust is a devastating fungal disease of wheat caused by Puccinia
      striiformis f. sp tritici (Pst). The WHEAT KINASE START1 (WKS1) resistance gene
      has an unusual combination of serine/threonine kinase and START lipid binding
      domains and confers partial resistance to Pst. Here, we show that wheat (Triticum
      aestivum) plants transformed with the complete WKS1 (variant WKS1.1) are
      resistant to Pst, whereas those transformed with an alternative splice variant
      with a truncated START domain (WKS1.2) are susceptible. WKS1.1 and WKS1.2
      preferentially bind to the same lipids (phosphatidic acid and
      phosphatidylinositol phosphates) but differ in their protein-protein
      interactions. WKS1.1 is targeted to the chloroplast where it phosphorylates the
      thylakoid-associated ascorbate peroxidase (tAPX) and reduces its ability to
      detoxify peroxides. Increased expression of WKS1.1 in transgenic wheat
      accelerates leaf senescence in the absence of Pst. Based on these results, we
      propose that the phosphorylation of tAPX by WKS1.1 reduces the ability of the
      cells to detoxify reactive oxygen species and contributes to cell death. This
      response takes several days longer than typical hypersensitive cell death
      responses, thus allowing the limited pathogen growth and restricted sporulation
      that is characteristic of the WKS1 partial resistance response to Pst. 

PMID- 25991737
TI  - Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine
      leiomyosarcoma and leiomyoma: something old and something new.
AB  - AIMS: To evaluate an immunohistochemical panel differentiating endometrial
      stromal sarcoma (ESS) from uterine leiomyosarcoma (ULMS) and leiomyoma (LM).
      METHODS: 94 cases (28 ESS, 41 ULMS, 25 LM) were retrieved and arrayed. 10
      immunomarkers (estrogen receptor (ER), progesterone receptor (PR), CD10, smooth
      muscle actin, desmin, h-caldesmon, transgelin, GEM, ASC1, stathmin1) were used. A
      predictive model was constructed and examined by receiver operating
      characteristics curve analysis to determine area under the curve (AUC). RESULTS:
      The combination of ER(+)/PR(+)/CD10(+)/GEM(-)/h-caldesmon(-)/transgelin(-) can
      predict ESS versus ULMS with AUC predictive value of 0.872 (95% CI 0.784 to
      0.961, p<0.0001). The combination of ER(+)/PR(+)/CD10(+)/h-caldesmon(
      )/transgelin(-) can predict low grade (LG) ESS from 'LG' ULMS with AUC predictive
      value of 0.914 (95% CI 0.832 to 0.995, p<0.0001). Finally, ULMS and ESS,
      including the LGs, were more likely to be stathmin1(+) than LM. CONCLUSIONS: Due
      to the different clinical course and management, adding novel antibodies (GEM,
      transgelin) to the well established immunohistochemistry panel seemed to be
      useful in distinguishing ESS from ULMS and LG ESS from 'LG' ULMS. Finally,
      stathmin1 expression could be of value in differentiating LM from uterine
      sarcomas.

PMID- 25991738
TI  - Application of RNA in situ hybridisation for identification of circulating tumour
      cells.

PMID- 25991736
TI  - The Rice High-Affinity Potassium Transporter1;1 Is Involved in Salt Tolerance and
      Regulated by an MYB-Type Transcription Factor.
AB  - Sodium transporters play key roles in plant tolerance to salt stress. Here, we
      report that a member of the High-Affinity K(+) Transporter (HKT) family,
      OsHKT1;1, in rice (Oryza sativa 'Nipponbare') plays an important role in reducing
      Na(+) accumulation in shoots to cope with salt stress. The oshkt1;1 mutant plants
      displayed hypersensitivity to salt stress. They contained less Na(+) in the
      phloem sap and accumulated more Na(+) in the shoots compared with the wild type.
      OsHKT1;1 was expressed mainly in the phloem of leaf blades and up-regulated in
      response to salt stress. Using a yeast one-hybrid approach, a novel MYB coiled
      coil type transcription factor, OsMYBc, was found to bind to the OsHKT1;1
      promoter. In vivo chromatin immunoprecipitation and in vitro electrophoresis
      mobility shift assays demonstrated that OsMYBc binds to AAANATNC(C/T) fragments
      within the OsHKT1;1 promoter. Mutation of the OsMYBc-binding nucleotides resulted
      in a decrease in promoter activity of OsHKT1;1. Knockout of OsMYBc resulted in a
      reduction in NaCl-induced expression of OsHKT1;1 and salt sensitivity. Taken
      together, these results suggest that OsHKT1;1 has a role in controlling Na(+)
      concentration and preventing sodium toxicity in leaf blades and is regulated by
      the OsMYBc transcription factor. 

PMID- 25991739
TI  - A novel NAP member GhNAP is involved in leaf senescence in Gossypium hirsutum.
AB  - Premature leaf senescence has a negative influence on the yield and quality of
      cotton, and several genes have been found to regulate leaf senescence. Howeer,
      many underlying transcription factors are yet to be identified. In this study, a
      NAP-like transcription factor (GhNAP) was isolated from Gossypium hirsutum. GhNAP
      has the typical NAC structure and a conserved novel subdomain in its divergent
      transcription activation region (TAR). GhNAP was demonstrated to be a nuclear
      protein, and it showed transcriptional activation activity in yeast. Furthermore,
      the expression of GhNAP was closely associated with leaf senescence. GhNAP could
      rescue the delayed-senescence phenotype of the atnap null mutant. Overexpression
      of GhNAP could cause precocious senescence in Arabidopsis. However, down
      regulation of GhNAP delayed leaf senescence in cotton, and affected cotton yield
      and its fibre quality. Moreover, the expression of GhNAP can be induced by
      abscisic acid (ABA), and the delayed leaf senescence phenotype in GhNAPi plants
      might be caused by the decreased ABA level and reduced expression level of ABA
      responsive genes. All of the results suggested that GhNAP could regulate the leaf
      senescence via the ABA-mediated pathways and was further related to the yield and
      quality in cotton.

PMID- 25991740
TI  - Triage during pandemic influenza: seeking absolution in numbers?

PMID- 25991741
TI  - Measurement of competence: achievable goal or 'holy grail'?

PMID- 25991743
TI  - Antral sonography in the paediatric patient: can transducer choice affect the
      view?

PMID- 25991742
TI  - Sepsis in Wales on the general wards: results of a feasibility pilot.

PMID- 25991744
TI  - Structured approach to ultrasound-guided identification of the cricothyroid
      membrane: a randomized comparison with the palpation method in the morbidly
      obese.

PMID- 25991745
TI  - French regional trauma network: the Rhone-Alpes example.

PMID- 25991746
TI  - Morphine is not a prodrug.

PMID- 25991747
TI  - Relative contribution of morphine and morphine-6-glucuronide to the analgesic
      effect after morphine administration.

PMID- 25991748
TI  - Difficult airway management and patient positioning in penetrating trauma.

PMID- 25991749
TI  - Continuous positive airway pressure during one-lung ventilation and disturbed
      visibility.

PMID- 25991750
TI  - Reduced local immune response with continuous positive airway pressure during one
      lung ventilation for oesophagectomy.

PMID- 25991757
TI  - Beta-blockade and other perioperative pharmacological protectors: what is now
      available and efficacious?

PMID- 25991758
TI  - A randomised feasibility study to assess a novel strategy to rationalise fluid in
      patients after cardiac surgery.
AB  - BACKGROUND: After cardiac surgery, patients receive large amounts of fluid in the
      Intensive Care Unit (ICU). We plan to conduct a multi-centre randomised
      controlled trial, of a conservative fluid regime, in patients after cardiac
      surgery, and have reported results of a feasibility study that evaluated efficacy
      and safety of the proposed regime. METHODS: After ethical approval, a single
      centre, prospectively randomised interventional study was undertaken.
      Participants were randomised to either usual care, or to a protocolised
      algorithm, utilising stroke volume variation, to guide fluid administration to
      patients who were deemed to have inadequate cardiac output and were likely to be
      volume responsive. The study protocol lasted from ICU admission to de-sedation or
      24 h, whichever occurred first. RESULTS: We randomised 144 subjects over 9
      months. Less bolus fluid and less total overall fluid volume was administered in
      the intervention group (median (IQR) 1620 ml (500-3410) and 2525 ml (1440-5250;
      P<0.001), compared with the usual care group (2050 ml (910-4280) and 2980 ml
      (2070-6580; P=0.001), from ICU admission to extubation. There was no significant
      difference in incidence of acute kidney injury or the average amount of fluid
      administered to the usual care group at the beginning compared with the end of
      the study. CONCLUSION: It is both possible and safe to achieve a significant
      reduction in the amount of fluid administered to patients, allocated to a
      conservative fluid protocol. These results suggest that a planned multi-centre
      study is both justified and feasible. CLINICAL TRIAL REGISTRATION: Australia New
      Zealand Clinical Trials Registry www.anzctr.org.au (ACTRN12612000754842).

PMID- 25991759
TI  - The NCEPOD study: on the right trach? lessons for the anaesthetist.

PMID- 25991760
TI  - Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled
      feasibility trial.
AB  - BACKGROUND: Low fibrinogen (Fg) concentrations in trauma haemorrhage are
      associated with poorer outcomes. Cryoprecipitate is the standard source for Fg
      administration in the UK and USA and is often given in the later stages of
      transfusion therapy. It is not known whether early cryoprecipitate therapy
      improves clinical outcomes. The primary aim of this feasibility study was to
      determine whether it was possible to administer cryoprecipitate, within 90 min of
      admission to hospital. Secondary aims were to evaluate laboratory measures of Fg
      and clinical outcomes including thrombotic events, organ failure, length of
      hospital stay and mortality. METHODS: This was an unblinded RCT, conducted at two
      civilian UK major trauma centres of adult trauma patients (age >=16 yrs), with
      active bleeding and requiring activation of the major haemorrhage protocol.
      Participants were randomised to standard major haemorrhage therapy (STANDARD)
      (n=22), or to standard haemorrhage therapy plus two early pools of
      cryoprecipitate (CRYO) (n=21). RESULTS: 85% (95% CI: 69-100%) CRYO participants
      received cryoprecipitate within 90 min, median time 60 min (IQR: 57-76) compared
      with 108 min (67-147), CRYO and STANDARD arms respectively (P=0.002). Fg
      concentrations were higher in the CRYO arm and were maintained above 1.8 g litre(
      1) at all time-points during active haemorrhage. All-cause mortality at 28 days
      was not significantly different (P=0.14). CONCLUSIONS: Early Fg supplementation
      using cryoprecipitate is feasible in trauma patients. This study supports the
      need for a definitive RCT to determine the effect of early Fg supplementation on
      mortality and other clinical outcomes. TRIAL REGISTRY NUMBER: ISRCTN55509212.

PMID- 25991761
TI  - Have case-register studies of eating disorders incidence reached their use-by
      date?

PMID- 25991762
TI  - Age at first tobacco use and risk of subsequent psychosis-related outcomes: A
      birth cohort study.
AB  - OBJECTIVE: Compared to the substantial body of research examining links between
      cannabis use and psychosis, there has been relatively little attention to the
      role of tobacco as a potential risk factor for psychosis. This study explored the
      association between age at first tobacco use and psychosis-related outcomes in a
      birth cohort. METHOD: This study is based on a large birth cohort (the Mater
      University Study of Pregnancy). At approximately 21 years of age, cohort members
      (N = 3752) were assessed for three psychosis-related outcomes (International
      Classification of Diseases non-affective psychosis, the presence of any
      hallucination and total count of delusional-like experiences) with the Composite
      International Diagnostic Interview and the Peters Delusional Inventory.
      Associations between age at first tobacco use and psychosis-related outcomes were
      examined using logistic regression in a model (a) adjusted for sex and age and
      (b) in a second model excluding all respondents who had a history of past
      problematic and current cannabis use. RESULTS: When adjusted for age and sex,
      those who commenced tobacco at 15 years of age or younger were significantly more
      likely to (a) have non-affective psychosis, (b) be in the highest quartile of
      total score of the Peters Delusional Inventory and (c) report hallucinations.
      After excluding all those with a history of a cannabis use disorder, or who were
      current (last month) cannabis users, a significant association between age at
      first tobacco use and the presence of hallucinations persisted. CONCLUSION: There
      is an association between age at first tobacco use and subsequent psychosis
      related outcomes in young adults. While the findings cannot be used to deduce
      causality, it adds weight to the hypothesis that early tobacco use may contribute
      to the risk of developing psychosis-related outcomes.

PMID- 25991763
TI  - Bipolar patients referred to specialized services of care: Not resistant but
      impaired by sub-syndromal symptoms. Results from the FACE-BD cohort.
AB  - OBJECTIVE: A national network of expert centers for bipolar disorders was set up
      in France to provide support, mainly for psychiatrists, who need help for
      managing bipolar disorder patients. The aims of this article are to present the
      main characteristics of the patients referred to an expert center in order to
      highlight the major disturbances affecting these patients and to understand the
      most significant difficulties encountered by practitioners dealing with bipolar
      disorder patients. METHODS: Patients were evaluated by trained psychiatrists and
      psychologists, with standardized and systematic assessment using interviews and
      self-report questionnaires. RESULTS: All patients (n = 839) met Diagnostic and
      Statistical Manual of Mental Disorders-Fourth Edition criteria for bipolar
      disorder I (48.4%), bipolar disorder II (38.1%) or bipolar disorder-not otherwise
      specified (13.5%). Mean illness duration was 17 years (+/-11.3), with 41.9% of
      patients having a history of suicide attempts. Lifetime comorbidities were 43.8%
      for anxiety disorders and 32.8% for substance abuse. At the point of inclusion,
      most patients (76.2%) were not in an acute phase, being considered to have a
      syndromal remission, but which still required referral to a tertiary system of
      care. Among these patients, 37.5% had mild to moderate residual depressive
      symptoms (Montgomery and Asberg Depression Rating Scale ranging from 7 to 19)
      despite 39% receiving an antidepressant. However, 47.8% were considered to be
      poorly adherent to medication; 55% showed evidence of sleep disturbances, with
      half being overweight; 68.1% of patients showed poor functioning (Functioning
      Assessment Short Test ? 12) with this being linked to residual depressive
      symptoms, sleep disturbances and increased body mass index. CONCLUSIONS: It
      appears that bipolar disorder patients referred to an expert center in most cases
      do not suffer from a severe or resistant illness but they rather have residual
      symptoms, including subtle but chronic perturbations that have a major impact on
      levels of functioning. The longitudinal follow-up of these patients will enable a
      better understanding of the evolution of such residual symptoms.

PMID- 25991764
TI  - Violence risk assessment in psychiatric patients in China: A systematic review.
AB  - OBJECTIVES: The aim of this study was to undertake a systematic review on
      violence risk assessment instruments used for psychiatric patients in China.
      METHODS: A systematic search was conducted from 1980 until 2014 to identify
      studies that used psychometric tools or structured instruments to assess
      aggression and violence risk. Information from primary studies was extracted,
      including demographic characteristics of the samples used, study design
      characteristics, and reliability and validity estimates. RESULTS: A total of 30
      primary studies were identified that investigated aggression or violence; 6
      reported on tools assessing aggression while an additional 24 studies reported on
      structured instruments designed to predict violence. Although measures of
      reliability were typically good, estimates of predictive validity were mostly in
      the range of poor to moderate, with only 1 study finding good validity. These
      estimates were typically lower than that found in previous work for Western
      samples. CONCLUSION: There is currently little evidence to support the use of
      current violence risk assessment instruments in psychiatric patients in China.
      Developing more accurate and scalable approaches are research priorities.

PMID- 25991766
TI  - Commentary: imaging appearances after endovascular aneurysm sealing with the
      Nellix system.

PMID- 25991765
TI  - Appearance of the Nellix endovascular aneurysm sealing system on computed
      tomography: implications for postoperative imaging surveillance.
AB  - PURPOSE: To describe the imaging characteristics of the Nellix Endovascular
      Aneurysm Sealing (EVAS) System on serial computed tomography (CT) surveillance.
      METHODS: Sixty-eight patients undergoing EVAS were enrolled in a surveillance
      protocol that included CT scans prior to hospital discharge and at 3, 6, and 9
      months postoperatively. Images were analyzed for the presence of gas within the
      endobag, endoleak, and for maximum radiodensity measured in Hounsfield units (HU)
      within the uppermost, middle, and lowermost regions of each endobag. RESULTS: Gas
      was seen within the endobags of all 68 EVAS repairs at the first postoperative CT
      compared with 2 (5.6%) of 36 undergoing the 3-month scan. The endobags appeared
      radiodense during initial imaging, and the median (interquartile range)
      radiodensity of the Nellix polymer decreased from 158.3 HU (149.5; 169.5) at the
      postoperative CT to 81.0 HU (74.0; 88.0) at 3 months, excluding 3 cases in which
      contrast pre-fill was utilized. Type I endoleak was seen at the periphery of the
      aneurysm sac or in the cleft between the endobags, with a substantially different
      appearance to endoleak after endovascular aneurysm repair. CONCLUSION: The
      evolution of CT appearances after EVAS was characteristic and predictable. The
      device endobags were initially radiodense, which may impact the detection of
      endoleak within 3 months of EVAS. Endoleaks after EVAS were seen in a different
      anatomical area to endoleaks after conventional stent-graft repair.

PMID- 25991767
TI  - Drug-Eluting vs Standard Balloon Angioplasty for Iliac Stent Restenosis: Midterm
      Results.
AB  - PURPOSE: To assess the effectiveness of drug-eluting balloon (DEB) angioplasty
      for the treatment of iliac artery in-stent restenosis (ISR). METHODS: Data from
      18 patients (mean age 59.3+/-9.6 years; 11 men) treated with DEB for iliac ISR
      between October 2009 and August 2013 were retrospectively evaluated and compared
      with a control group of 22 patients (mean age 66.7+/-11.8 years; 16 men) treated
      with standard balloon angioplasty (BA). Primary endpoint of the study was the
      primary patency rate at 12 months. Secondary endpoints were 30-day and overall
      mortality, sustained clinical improvement [ankle-brachial index (ABI) and
      Rutherford category] and clinically driven target lesion revascularization (TLR).
      Follow-up examinations were performed by clinical examination, color duplex
      ultrasound, and ABI measurement at 12 months. RESULTS: Mean length of the 21
      lesions in the DEB group was 27.1+/-19.2 mm vs 20.0+/-11.4 mm for the 25 lesions
      in the BA group (p=0.508), while the grade of restenosis was 70.4%+/-18.4% and
      64.0%+/-16.1% (p=0.255), respectively. Primary patency rates were 90.5% vs 85.7%
      at 6 months and 71.4% vs 75.6% at 12 months for DEB and BA, respectively
      (p=0.784). Five BA patients died during follow-up for reasons unrelated to the
      procedure, while no patient in the DEB group died (p=0.035). In both groups,
      Rutherford category and ABI significantly improved compared to pretreatment
      levels; there were no differences between the groups regarding these variables
      (p=0.367 and p=0.898, respectively). The TLR rate was 28.6% (6/21) in the DEB
      group and 20.0% (4/20) in the BA cohort (p=0.434). CONCLUSION: Treatment of iliac
      ISR using DEBs is a safe procedure, with results comparable to BA treatment.
      Because of the limited number of patients in this study, further investigation of
      a larger cohort with longer follow-up is needed to define the role of DEBs in the
      treatment of iliac ISR.

PMID- 25991768
TI  - Pragmatic minimum reporting standards for thoracic endovascular aortic repair.

PMID- 25991769
TI  - Commentary: occlusion of parallel/bridging stent-grafts in the treatment of
      complex aneurysms: a purely technical issue . . . Or not?

PMID- 25991771
TI  - Corrigendum.

PMID- 25991770
TI  - Studying the interaction of stent-grafts and treated abdominal aortic aneurysms:
      time to move caudally!
AB  - Since the advent of endovascular repair of aortic aneurysms (EVAR), clinical
      focus has been on preventing loss of sealing at the level of the infrarenal neck,
      which leads to type I endoleak and repressurization of the aneurysm sac. Enhanced
      mechanisms for central fixation and seal have consequently lowered the incidence
      of migration and endoleaks. However, endograft limb thrombosis and its causal
      mechanisms have not been addressed adequately in the literature. This article
      reviews the pathophysiological mechanisms associated with limb thrombosis in
      order to facilitate better clinical judgment to prevent iliac adverse effects. 

PMID- 25991772
TI  - ...now the Royal College of Emergency Medicine.

PMID- 25991773
TI  - My fingers are discoloured.

PMID- 25991774
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: use of a procalcitonin algorithm to guide antimicrobial therapy
      in COPD exacerbations can reduce antibiotic consumption with no increase in rates
      of treatment failure or mortality.
AB  - A shortcut review was carried out to establish whether a procalcitonin-guided
      algorithm could safely reduce antibiotic consumption for patients with an
      exacerbation of chronic obstructive pulmonary disease attending the emergency
      department. Four randomised controlled trials were found directly relevant to the
      three-part question, combined within a later systematic review and meta-analysis.
      A further prospective cohort study was also found relevant to the three-part
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      tabulated. The clinical bottom line is that a procalcitonin algorithm appears to
      be a useful strategy to guide initiation and duration of antibiotics and can
      reduce consumption without conferring additional risk. However, no cost
      effectiveness data are available as yet and further validation studies are
      required prior to widespread recommendation. 

PMID- 25991776
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: negative B natriuretic peptide testing confirms low risk
      stratification for patients with a definite pulmonary embolus.
AB  - A shortcut review was carried out to establish whether a negative B natriuretic
      peptide could identify patients with confirmed pulmonary embolus at low risk for
      a complicated clinical course and therefore potentially suitable for outpatient
      therapy. Two systematic review/meta-analyses were found directly relevant to the
      three-part question. A further six prospective cohort studies of high quality
      postdating the systematic review were also found, relevant to the three-part
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      tabulated. The clinical bottom line is that in normotensive patients with
      confirmed pulmonary embolism, a negative B natriuretic peptide or NTProBNP
      confers a low clinical risk of complications. When used in addition to a clinical
      risk scoring system such as the simplified pulmonary severity index, the risk
      becomes negligible (<1%). Such patients could be considered for outpatient
      therapy direct from the emergency department. 

PMID- 25991801
TI  - Capturing complexity: socioeconomic disadvantage and heart failure outcomes.

PMID- 25991802
TI  - Garbage in, gospel out: ignoring goals of care when assessing heart failure
      quality metrics.

PMID- 25991803
TI  - Updating the physiology and pathophysiology of cardiac Myosin-binding protein-C.

PMID- 25991804
TI  - Autonomic modulation for the management of patients with chronic heart failure.

PMID- 25991805
TI  - Sharing the care of mechanical circulatory support: collaborative efforts of
      patients/caregivers, shared-care sites, and left ventricular assist device
      implanting centers.

PMID- 25991807
TI  - Heart failure due to adrenergic myocardial toxicity from a pheochromocytoma.

PMID- 25991806
TI  - Comparing Sodium Intake Strategies in Heart Failure: Rationale and Design of the
      Prevent Adverse Outcomes in Heart Failure by Limiting Sodium (PROHIBIT) Study.

PMID- 25991809
TI  - Ventricular square-wave response: case illustrating the role of invasive
      hemodynamics in the management of continuous-flow left ventricular assist device
      dysfunction.

PMID- 25991808
TI  - Platelet inhibition with ticagrelor for left ventricular assist device
      thrombosis.

PMID- 25991810
TI  - Arbuscular mycorrhizal fungal diversity associated with Eleocharis obtusa and
      Panicum capillare growing in an extreme petroleum hydrocarbon-polluted
      sedimentation basin.
AB  - Arbuscular mycorrhizal fungi (AMF) have been extensively studied in natural and
      agricultural ecosystems, but little is known about their diversity and community
      structure in highly petroleum-polluted soils. In this study, we described an
      unexpected diversity of AMF in a sedimentation basin of a former petrochemical
      plant, in which petroleum hydrocarbon (PH) wastes were dumped for many decades.
      We used high-throughput PCR, cloning and sequencing of 18S rDNA to assess the
      molecular diversity of AMF associated with Eleocharis obtusa and Panicum
      capillare spontaneously inhabiting extremely PH-contaminated sediments. The
      analyses of rhizosphere and root samples over two years showed a remarkable AMF
      richness comparable with that found in temperate natural ecosystems. Twenty-one
      taxa, encompassing the major families within Glomeromycota, were detected. The
      most abundant OTUs belong to genera Claroideoglomus, Diversispora, Rhizophagus
      and Paraglomus. Both plants had very similar overall community structures and OTU
      abundances; however, AMF community structure differed when comparing the overall
      OTU distribution across the two years of sampling. This could be likely explained
      by variations in precipitations between 2011 and 2012. Our study provides the
      first view of AMF molecular diversity in soils extremely polluted by PH, and
      demonstrated the ability of AMF to colonize and establish in harsh environments. 

PMID- 25991811
TI  - Relation between cell death progression, reactive oxygen species production and
      mitochondrial membrane potential in fermenting Saccharomyces cerevisiae cells
      under heat-shock conditions.
AB  - Moderate heat shock increased reactive oxygen species (ROS) production that led
      to cell death in glucose-grown Saccharomyces cerevisiae cells. Conditions that
      disturb mitochondrial functions such as treatment by uncouplers and petite
      mutation were shown to inhibit ROS production and protects cell from thermal
      death. Hence, mitochondria are responsible for ROS production and play an active
      role in cell death. An increase in ROS production was accompanied by
      hyperpolarization of inner mitochondrial membrane. All agents suppressing
      hyperpolarization also suppressed heat-induced ROS production. It was supposed
      that generation of ROS under moderate heat shock in glucose-grown S. cerevisiae
      cells is driven by the mitochondrial membrane potential. 

PMID- 25991812
TI  - CD8+ T Cells Regulate Monopoiesis and Circulating Ly6C-high Monocyte Levels in
      Atherosclerosis in Mice.
AB  - RATIONALE: Proinflammatory adaptive immune responses are recognized as major
      drivers of atherosclerotic lesion formation. Although CD8(+) T cells have
      recently been proposed as a proatherogenic cell subset, their full scope of
      actions remains to be elucidated. OBJECTIVE: We here addressed the contribution
      of CD8(+) T cells to monocyte trafficking in atherosclerosis. METHOD AND RESULTS:
      We observed that CD8(+) T cells express proinflammatory cytokines (interferon
      gamma, tumor necrosis factor-alpha, and interleukin-12) within atherosclerotic
      lesions and spleens of high-fat diet-fed low-density lipoprotein receptor
      deficient (Ldlr(-/-)) mice. Antibody-mediated CD8(+) T-cell depletion in high-fat
      diet-fed Ldlr(-/-) mice decreased atherosclerotic plaque formation, associated
      with decreased macrophage accumulation within lesions. Despite a reduction in
      vascular chemokine (CC-motif) ligand 2 and chemokine (CXC-motif) ligand 1
      expression, CD8(+) T-cell depletion did not directly affect monocyte recruitment
      to inflamed vessels. However, CD8(+) T-cell depletion decreased chemokine (CC
      motif) ligand serum concentrations and circulating Ly6C(high) monocyte counts. We
      further evidenced that CD8(+) T-cell depletion decreased levels of mature
      monocytes and myeloid granulocyte-monocyte progenitors in the bone marrow and
      spleen of hypercholesterolemic mice, effects that were partially reproduced by
      interferon-gamma neutralization, showing a role for interferon-gamma.
      CONCLUSIONS: These data suggest that CD8(+) T cells promote atherosclerosis by
      controlling monopoiesis and circulating monocyte levels, which ultimately
      contributes to plaque macrophage burden without affecting direct monocyte
      recruitment, identifying this cell subset as a critical regulator of
      proatherogenic innate immune cell responses in atherosclerosis.

PMID- 25991813
TI  - Endoscopic management of refractory gastrointestinal non-variceal bleeding using
      Histoacryl (N-butyl-2-cyanoacrylate) glue.
AB  - BACKGROUND: Histoacryl glue (N-butyl-2-cyanoacrylate) has well-established
      utility in the endoscopic management of gastrointestinal variceal bleeding. The
      role of Histoacryl glue in non-variceal bleeding is less clear, and there are few
      articles describing its use in this setting. METHODS: Six patients with
      intractable non-variceal gastrointestinal bleeding were managed using injection
      of Histoacryl glue. All patients had previously failed conventional endostasis
      and/or interventional angioembolization and were not suitable for emergency
      salvage surgery due to serious comorbidities or unacceptable anaesthetic risk. An
      endoscopic Lipiodol-Histoacryl-Lipiodol sandwich injection technique was used in
      these patients. The clinical outcomes and complications were evaluated. RESULTS:
      There were four females and two males with a mean age of 55 years. Bleeding
      lesions included gastric ulcers (n = 2), duodenal ulcers (n = 2), duodenal
      gastrointestinal stromal tumor (GIST) (n = 1) and rectal ulcers (n = 1). All
      patients had successful Histoacryl endostasis without the requirement for salvage
      surgery. There was no treatment-related morbidity and no mortality. Two patients
      had further bleeding after initial Histoacryl endostasis, which was successfully
      controlled with further endoscopic Histoacryl injection. CONCLUSION: Histoacryl
      endostasis should be included in the treatment algorithm for refractory non
      variceal gastrointestinal bleeding.

PMID- 25991814
TI  - Selection on horizontally transferred and duplicated genes in sinorhizobium
      (ensifer), the root-nodule symbionts of medicago.

PMID- 25991815
TI  - Genome Diversity and Divergence in Drosophila mauritiana: Multiple Signatures of
      Faster X Evolution.

PMID- 25991816
TI  - Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal
      Lesions.
AB  - PURPOSE: Colorectal cancer remains the second leading cause of cancer deaths in
      the United States despite being eminently preventable by colonoscopy via removal
      of premalignant adenomas. In order to more effectively reduce colorectal cancer
      mortality, improved screening paradigms are needed. Our group pioneered the use
      of low-coherence enhanced backscattering (LEBS) spectroscopy to detect the
      presence of adenomas throughout the colon via optical interrogation of the rectal
      mucosa. In a previous ex vivo biopsy study of 219 patients, LEBS demonstrated
      excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The
      objective of the current cross-sectional study is to assess the viability of
      rectal LEBS in vivo. EXPERIMENTAL DESIGN: Measurements from 619 patients were
      taken using a minimally invasive 3.4-mm diameter LEBS probe introduced into the
      rectum via anoscope or direct insertion, requiring approximately 1 minute from
      probe insertion to withdrawal. The diagnostic LEBS marker was formed as a
      logistic regression of the optical reduced scattering coefficient [Formula: see
      text] and mass density distribution factor D. RESULTS: The rectal LEBS marker was
      significantly altered in patients harboring advanced adenomas and multiple non
      advanced adenomas throughout the colon. Blinded and cross-validated test
      performance characteristics showed 88% sensitivity to advanced adenomas, 71%
      sensitivity to multiple non-advanced adenomas, and 72% specificity in the
      validation set. CONCLUSIONS: We demonstrate the viability of in vivo LEBS
      measurement of histologically normal rectal mucosa to predict the presence of
      clinically relevant adenomas throughout the colon. The current work represents
      the next step in the development of rectal LEBS as a tool for colorectal cancer
      risk stratification.

PMID- 25991818
TI  - Spatiotemporal Heterogeneity Characterizes the Genetic Landscape of
      Pheochromocytoma and Defines Early Events in Tumorigenesis.
AB  - PURPOSE: Pheochromocytoma and paraganglioma (PPGL) patients display heterogeneity
      in the clinical presentation and underlying genetic cause. The degree of inter-
      and intratumor genetic heterogeneity has not yet been defined. EXPERIMENTAL
      DESIGN: In PPGLs from 94 patients, we analyzed LOH, copy-number variations, and
      mutation status of SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, NF1, RET, TMEM127,
      MAX, and HRAS using high-density SNP array and targeted deep sequencing,
      respectively. Genetic heterogeneity was determined through (i) bioinformatics
      analysis of individual samples that estimated absolute purity and ploidy from SNP
      array data and (ii) comparison of paired tumor samples that allowed
      reconstruction of phylogenetic trees. RESULTS: Mutations were found in 61% of the
      tumors and correlated with specific patterns of somatic copy-number aberrations
      (SCNA) and degree of nontumoral cell admixture. Intratumor genetic heterogeneity
      was observed in 74 of 136 samples using absolute bioinformatics estimations and
      in 22 of 24 patients by comparison of paired samples. In addition, a low genetic
      concordance was observed between paired primary tumors and distant metastases.
      This allowed for reconstructing the life history of individual tumors,
      identifying somatic mutations as well as copy-number loss of 3p and 11p (VHL
      subgroup), 1p (Cluster 2), and 17q (NF1 subgroup) as early events in PPGL
      tumorigenesis. CONCLUSIONS: Genomic landscapes of PPGL are specific to mutation
      subtype and characterized by genetic heterogeneity both within and between tumor
      lesions of the same patient.

PMID- 25991817
TI  - Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine
      Therapy-Resistant Breast Cancer.
AB  - PURPOSE: Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains
      first-line therapy for the management of estrogen receptor (ESR1)-positive breast
      cancer. However, ESR1 mutations or other ligand-independent ESR1 activation
      mechanisms limit the duration of response. The clinical efficacy of fulvestrant,
      a selective estrogen receptor downregulator (SERD) that competitively inhibits
      agonist binding to ESR1 and triggers receptor downregulation, has confirmed that
      ESR1 frequently remains engaged in endocrine therapy-resistant cancers. We
      evaluated the activity of a new class of selective estrogen receptor modulators
      (SERM)/SERD hybrids (SSH) that downregulate ESR1 in relevant models of endocrine
      resistant breast cancer. Building on the observation that concurrent inhibition
      of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased
      progression-free survival in advanced patients, we explored the activity of
      different SERD- or SSH-CDK4/6 inhibitor combinations in models of endocrine
      therapy-resistant ESR1(+) breast cancer. EXPERIMENTAL DESIGN: SERDs, SSHs, and
      the CDK4/6 inhibitor palbociclib were evaluated as single agents or in
      combination in established cellular and animal models of endocrine therapy
      resistant ESR1(+) breast cancer. RESULTS: The combination of palbociclib with a
      SERD or an SSH was shown to effectively inhibit the growth of MCF7 cell or ESR1
      mutant patient-derived tumor xenografts. In tamoxifen-resistant MCF7 xenografts,
      the palbociclib/SERD or SSH combination resulted in an increased duration of
      response as compared with either drug alone. CONCLUSIONS: A SERD- or SSH
      palbociclib combination has therapeutic potential in breast tumors resistant to
      endocrine therapies or those expressing ESR1 mutations. See related commentary by
      DeMichele and Chodosh, p. 4999.

PMID- 25991819
TI  - Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central
      Nervous System Lymphomas.
AB  - PURPOSE: Primary central nervous system lymphoma (PCNSL) is an aggressive non
      Hodgkin lymphoma confined to the central nervous system. Whether there is a PCNSL
      specific genomic signature and, if so, how it differs from systemic diffuse large
      B-cell lymphoma (DLBCL) is uncertain. EXPERIMENTAL DESIGN: We performed a
      comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL
      patients. Testing comprised array-comparative genomic hybridization and whole
      exome sequencing. RESULTS: Biallelic inactivation of TOX and PRKCD was
      recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role
      in PCNSL pathogenesis. In addition, we found a high prevalence of MYD88 mutations
      (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in
      PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13,
      TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11, and
      translocations IgH-BCL6. Overall, B-cell receptor/Toll-like receptor/NF-kappaB
      pathways were altered in >90% of PNCSL, highlighting its value for targeted
      therapeutic approaches. Furthermore, integrated analysis showed enrichment of
      pathways associated with immune response, proliferation, apoptosis, and
      lymphocyte differentiation. CONCLUSIONS: In summary, genome-wide analysis
      uncovered novel recurrent alterations, including TOX and PRKCD, helping to
      differentiate PCNSL from systemic DLBCL and related lymphomas.

PMID- 25991821
TI  - Untouched GMP-Ready Purified Engineered Immune Cells to Treat Cancer.
AB  - PURPOSE: Engineering T cells with receptors to redirect the immune system against
      cancer has most recently been described as a scientific breakthrough. However, a
      main challenge remains the GMP-grade purification of immune cells selectively
      expressing the introduced receptor in order to reduce potential side effects due
      to poorly or nonengineered cells. EXPERIMENTAL DESIGN: In order to test a novel
      purification strategy, we took advantage of a model gammadeltaT cell receptor
      (TCR), naturally interfering with endogenous TCR expression and designed the
      optimal retroviral expression cassette to achieve maximal interference with
      endogenous TCR chains. Following retroviral transduction, nonengineered and
      poorly engineered immune cells characterized by a high endogenous alphabetaTCR
      expression were efficiently depleted with GMP-grade anti-alphabetaTCR beads.
      Next, the engineered immune cells were validated for TCR expression, function
      against a panel of tumor cell lines and primary tumors and potential allo
      reactivity. Engineered immune cells were further validated in two humanized mouse
      tumor models. RESULTS: The untouched enrichment of engineered immune cells
      translated into highly purified receptor-engineered cells with strong antitumor
      reactivity both in vitro and in vivo. Importantly, this approach eliminated
      residual allo-reactivity of engineered immune cells. Our data demonstrate that
      even with long-term suboptimal interference with endogenous TCR chains such as in
      resting cells, allo-reactivity remained absent and tumor control preserved.
      CONCLUSIONS: We present a novel enrichment method for the production of untouched
      engineered immune cells, ready to be translated into a GMP-grade method and
      potentially applicable to all receptor-modified cells even if interference with
      endogenous TCR chains is far from complete.

PMID- 25991820
TI  - Emerging Treatment Paradigms in Radiation Oncology.
AB  - Rapid advancements in radiotherapy and molecularly targeted therapies have
      resulted in the development of potential paradigm-shifting use of radiotherapy in
      the treatment of cancer. In this review, we discuss some of the most promising
      therapeutic approaches in the field of radiation oncology. These strategies
      include the use of highly targeted stereotactic radiotherapy and particle therapy
      as well as combining radiotherapy with agents that modulate the DNA damage
      response, augment the immune response, or protect normal tissues.

PMID- 25991824
TI  - Application of the characteristic function to evaluate and compare analytical
      variability in an external quality assessment scheme for serum ethanol.
AB  - BACKGROUND: As a cornerstone of quality management in the laboratory, External
      Quality Assessment (EQA) schemes are used to assess laboratory and analytical
      method performance. The characteristic function is used to describe the relation
      between the target concentration and the EQA standard deviation, which is an
      essential part of the evaluation process. The characteristic function is also
      used to compare the variability of different analytical methods. METHODS: We
      fitted the characteristic function to data from the Belgian External Quality
      Assessment program for serum ethanol. Data included results from headspace gas
      chromatography and the enzymatic methods of Abbott, Roche, Siemens, and Ortho
      Clinical Diagnostics. We estimated the characteristic function with weighted
      nonlinear regression. By introducing dummy variables, we rewrote the original
      formula of the characteristic function to assess statistical inference for
      comparing the variability of the different analytical methods. RESULTS: The
      characteristic function fitted the data precisely. Comparison between methods
      showed that there was little difference between the estimated variability for low
      concentrations, and that the increase in SD with increasing target concentration
      was slower for Abbott and Roche than for the other methods. CONCLUSIONS: The
      characteristic function can successfully be introduced in clinical schemes,
      although its applicability to fit the data should always be assessed. Because of
      its easy parameterization, it can be used to assess differences in performance
      between analytical methods and to assess laboratory performance. The
      characteristic function also offers an alternative framework for coefficients of
      variation to describe variability of analytical methods.

PMID- 25991822
TI  - Parasexual Ploidy Reduction Drives Population Heterogeneity Through Random and
      Transient Aneuploidy in Candida albicans.
AB  - The opportunistic pathogen Candida albicans has a large repertoire of mechanisms
      to generate genetic and phenotypic diversity despite the lack of meiosis in its
      life cycle. Its parasexual cycle enables shifts in ploidy, which in turn
      facilitate recombination, aneuploidy, and homozygosis of whole chromosomes to
      fuel rapid adaptation. Here we show that the tetraploid state potentiates ploidy
      variation and drives population heterogeneity. In tetraploids, the rate of losing
      a single heterozygous marker [loss of heterozygosity (LOH)] is elevated ~30-fold
      higher than the rate in diploid cells. Furthermore, isolates recovered after
      selection for LOH of one, two, or three markers were highly aneuploid, with a
      broad range of karyotypes including strains with a combination of di-, tri-, and
      tetrasomic chromosomes. We followed the ploidy trajectories for these tetraploid-
      and aneuploid-derived isolates, using a combination of flow cytometry and double
      digestion restriction-site-associated DNA analyzed with next-generation
      sequencing. Isolates derived from either tetraploid or aneuploid isolates
      predominately resolved to a stable euploid state. The majority of isolates
      reduced to the conventional diploid state; however, stable triploid and
      tetraploid states were observed in ~30% of the isolates. Notably, aneuploid
      isolates were more transient than tetraploid isolates, resolving to a euploid
      state within a few passages. Furthermore, the likelihood that a particular
      isolate will resolve to the same ploidy state in replicate evolution experiments
      is only ~50%, supporting the idea that the chromosome loss process of the
      parasexual cycle is random and does not follow trajectories involving specific
      combinations of chromosomes. Together, our results indicate that tetraploid
      progenitors can produce populations of progeny cells with a high degree of
      genomic diversity, from altered ploidy to homozygosis, providing an excellent
      source of genetic variation upon which selection can act.

PMID- 25991825
TI  - When change is not a good thing.

PMID- 25991823
TI  - Virulence Gene Regulation by L-Arabinose in Salmonella enterica.
AB  - Invasion of the intestinal epithelium is a critical step in Salmonella enterica
      infection and requires functions encoded in the gene cluster known as Salmonella
      Pathogenicity Island 1 (SPI-1). Expression of SPI-1 genes is repressed by L
      arabinose, and not by other pentoses. Transport of L-arabinose is necessary to
      repress SPI-1; however, repression is independent of L-arabinose metabolism and
      of the L-arabinose-responsive regulator AraC. SPI-1 repression by L-arabinose is
      exerted at a single target, HilD, and the mechanism appears to be post
      translational. As a consequence of SPI-1 repression, l-arabinose reduces
      translocation of SPI-1 effectors to epithelial cells and decreases Salmonella
      invasion in vitro. These observations reveal a hitherto unknown role of L
      arabinose in gene expression control and raise the possibility that Salmonella
      may use L-arabinose as an environmental signal.

PMID- 25991826
TI  - Effects of Exercise Training on Regulation of Skeletal Muscle Glucose Metabolism
      in Elderly Men.
AB  - BACKGROUND: The aim was to investigate the molecular mechanisms behind exercise
      training-induced improvements in glucose regulation in aged subjects. METHODS:
      Twelve elderly male subjects completed 8 weeks of exercise training. Before and
      after the training period, the subjects completed an oral glucose tolerance test
      (OGTT) and a muscle biopsy was obtained from the vastus lateralis before and 45
      minutes into the OGTT. Blood samples were collected before and up to 120 minutes
      after glucose intake. RESULTS: Exercise training increased Hexokinase II, GLUT4,
      Akt2, glycogen synthase (GS), pyruvate dehydrogenase (PDH)-E1alpha, PDK2 protein,
      and glycogen content in skeletal muscle. Furthermore, in response to glucose, GS
      activity was increased and the dephosphorylation of GS site 2 + 2a and 3a was
      enhanced after the training intervention. The glucose-mediated insulin
      stimulation of TBC1D4 Thr(642) phosphorylation was increased after exercise
      training. In the trained state, the PDHa activity was reduced following glucose
      intake and without changes in phosphorylation level of PDH-E1alpha. CONCLUSIONS:
      The present results suggest that exercise training improves glucose regulation in
      elderly subjects by enhancing the capacity and acute regulation of glucose uptake
      and by enhancing intracellular glucose removal to glycogen synthesis rather than
      glucose oxidation.

PMID- 25991828
TI  - Now, the Taller Die Earlier: The Curse of Cancer.
AB  - This study estimates the relationship between height and mortality. Individuals
      in the National Health Interview Survey 1986, a nationally representative U.S.
      sample, are linked to death certificate data until December 31, 2006. We analyze
      this relationship in 14,440 men and 16,390 women aged 25+. We employ the Cox
      proportional hazards model, controlling for birthday and education. An additional
      inch increase in height is related to a hazard ratio of death from all causes
      that is 2.2% higher for men and 2.5% higher for women. The findings are robust to
      changing survival distributions, and further analyses indicate that the figures
      are lower bounds. This relationship is mainly driven by the positive relationship
      between height and development of cancer. An additional inch increase in height
      is related to a hazard ratio of death from malignant neoplasms that is 7.1%
      higher for men and 5.7% higher for women. In contrast to the negative
      relationship between height and mortality in the past, this relationship is now
      positive. This demonstrates the success and accessibility of medical technology
      in treating patients with many acute and chronic diseases other than cancer.

PMID- 25991827
TI  - Aerobic Exercise Recovers Disuse-induced Atrophy Through the Stimulus of the
      LRP130/PGC-1alpha Complex in Aged Rats.
AB  - Physical training has been shown to be important to the control of muscle mass
      during aging, through the activation of several pathways including, IGF1-AKT and
      PGC-1alpha. Also, it was demonstrated that LRP130, a component of the PGC-1alpha
      complex, is important for the PGC-1alpha-dependent transcription of several
      mitochondrial genes in vivo. To explore the role of physical training during
      aging, we investigated the effects on muscle recovery after short-term
      immobilization followed by 3 or 7 days with aerobic or resistance training. Using
      morphological (myofibrillar adenosine triphosphatase activity, to assess the
      total muscle fiber cross-sectional area (CSA) and the frequency of specific fiber
      types), biochemical (myosin heavy chain), and molecular analyses (quantitative
      real-time PCR, functional pathways analyses, and Western blot), our results
      indicated that after an atrophic stimulus, only animals subjected to aerobic
      training showed entire recovery of cross-sectional area; aerobic training reduced
      the ubiquitin-proteasome system components involved in muscle atrophy after 3
      days of recovery, and the upregulation in PGC-1alpha expression enhanced the
      process of muscle recovery by inhibiting the FoxO pathway, with the possible
      involvement of LRP130. These results suggest that aerobic training enhanced the
      muscle regeneration process after disuse-induced atrophy in aged rats possibly
      through of the LRP130/PGC-1alpha complex by inhibiting the ubiquitin-proteasome
      system. 

PMID- 25991829
TI  - Disentangling the Impact of Chronic Kidney Disease, Anemia, and Mobility
      Limitation on Mortality in Older Patients Discharged From Hospital.
AB  - BACKGROUNDS: Chronic kidney disease (CKD), anemia, and mobility limitation are
      important predictors of mortality. We aimed at investigating the interactions
      between estimated glomerular filtration rate (eGFR), anemia, and physical
      performance on 1-year mortality in older patients discharged from acute care
      hospitals. METHODS: Four hundred and eighty seven patients enrolled in a
      multicenter, prospective observational study were included in the analysis. eGFR
      was estimated by the Berlin Initiative Study 1 equation. Anemia was defined on
      the basis of hemoglobin values. Mobility limitation was rated by the Short
      Physical Performance Battery (SPPB). Covariates included demographics,
      nutritional status, cognitive performance, and comorbidity. The outcome of the
      study was mortality over 1-year follow-up. Interactions among study variables
      were investigated by survival tree analysis. RESULTS: eGFR < 30 mL/min/1.73 m(2),
      anemia, and SPPB = 0-4 were significantly associated with mortality, as were
      hypoalbuminemia and cognitive impairment. Survival tree analysis showed that
      compared to patients with SPPB >= 4 and eGFR >= 46.7 mL/min/1.73 m(2) (ie,
      patients with the least mortality), patients with SPPB < 4 and hemoglobin < 12.2
      g/dL had the highest risk of mortality [hazard ratio (HR) = 28.9, 95%CI 10.3
      81.2]. Patients with SPPB >= 4 and eGFR < 46.7 mL/min/1.73 m(2) and those with
      SPPB > 4, hemoglobin >= 12.2g/dL, and eGFR >= 58.6 mL/min/1.73 m(2) had
      intermediate risk (HR = 6.58, 95%CI = 2.15-20.2, and HR = 15.11, 95%CI=4.42-51.7,
      respectively). Having SPPB < 4, hemoglobin >= 12.2 g/dL, and eGFR<58.6
      mL/min/l.73 m(2) was not significantly associated with increased mortality (HR =
      2.95, 95%CI = 0.74-11.8). CONCLUSIONS: Interactions among eGFR, anemia, and
      mobility limitation define different profiles of risk in older patients
      discharged from acute care hospitals, which deserve to be considered to identify
      patients needing special care and careful follow-up after discharge.

PMID- 25991830
TI  - Attention to deficits of mixed mood states: Hype or activity?

PMID- 25991831
TI  - Evaluation of a Pharmacist-Directed Vancomycin Dosing and Monitoring Pilot
      Program at a Tertiary Academic Medical Center.
AB  - BACKGROUND: Consensus guidelines recommend vancomycin doses of 15 to 20 mg/kg
      every 8 to 12 hours in patients with normal renal function. OBJECTIVE: To
      evaluate the effect of a pharmacist-directed vancomycin dosing and monitoring
      pilot program on the percentage of patients receiving targeted weight-based
      dosing recommendations. METHODS: This was a pre-/postevaluation study, approved
      by the institutional review board at our institution, comparing retrospectively
      reviewed vancomycin dosing practices hospital-wide between September 1 and
      September 30, 2010 to patients prospectively managed by a pharmacist-directed
      vancomycin pilot program between February 1 and April 26, 2011. All adult
      inpatients receiving intravenous vancomycin were included, unless patients had a
      creatinine clearance less than or equal to 60 mL/min or indication for therapy
      was surgical prophylaxis or febrile neutropenia. The primary outcome was the
      percentage of patients who received optimal vancomycin dosing defined as >=30
      mg/kg/d within 24 hours of initiation of therapy. Secondary outcomes included
      number of pharmacist interventions, length of therapy and incidence of
      nephrotoxicity while receiving vancomycin. RESULTS: A total of 319 patients were
      analyzed, 161 preimplementation and 158 postimplementation. The percentage of
      patients who received optimal vancomycin dosing was significantly higher
      postimplementation of the pilot program, 96.8 versus 40.4% (P < 0.001).
      Pharmacist-directed interventions postimplementation, resulted in 50% more
      patients being dosed optimally (P < 0.001). Patients in the pilot program also
      had a shorter length of therapy (10.0 vs 8.4 days, P < 0.003) and a lower
      incidence of nephrotoxicity (8.7% vs 3.2%, P = 0.006). CONCLUSIONS: This
      pharmacist-directed vancomycin pilot program significantly increased the
      percentage of patients optimally dosed according to consensus guidelines within
      24 hours of initiation of therapy.

PMID- 25991832
TI  - Current status and future directions of the immune checkpoint inhibitors
      ipilimumab, pembrolizumab, and nivolumab in oncology.
AB  - OBJECTIVE: To provide the clinician with an update and the current status and
      future direction of approved immune checkpoint inhibitors (ICIs) in oncology.
      DATA SOURCES: A PubMed search from January 1, 1966 to March 13, 2015 was
      performed using the key terms ipilimumab, pembrolizumab, lambrolizumab,
      nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475,
      SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer,
      oncology, or neoplasm. Additional references were identified from the
      investigators(') personal files, recent oncology meetings, review articles,
      clinical guidelines, and package inserts. STUDY SELECTION AND DATA EXTRACTION:
      All English-language clinical trials assessing the safety and efficacy of
      ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed
      search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials
      were identified from the above sources; 61 trials from 2005 to 2015 were
      included. We consolidated and clarified treatment recommendations for the
      management of immune-related adverse events (irAEs), assessed response criteria,
      and calculated the clinical utility of leading tumor profiling options. DATA
      SYNTHESIS: Ipilimumab and nivolumab, but not pembrolizumab, have an overall
      survival (OS) advantage over chemotherapy first line in unresectable/metastatic
      melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line
      squamous non-small-cell lung cancer. Data in other settings are promising.
      Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further
      validation of response criteria is needed. Tumor profiling to predict clinical
      benefit is premature but promising. CONCLUSIONS: The treatment landscape in
      oncology is quickly evolving with the advent of ICIs.

PMID- 25991833
TI  - Alar Suspension Sutures in the Management of Nasal Valve Collapse.
AB  - OBJECTIVE: This study assesses the efficacy of alar suspension sutures in the
      management of nasal valve collapse causing nasal obstruction. These sutures are
      inserted between the vestibular skin and lateral crura and hitched to the
      periosteum of the medial inferior orbital margin; this is a variation of the alar
      (change everywhere) suspension suture technique. METHOD: A retrospective review
      of patients who underwent alar suspension suture insertion between January 2009
      and December 2010 in the management of nasal obstruction was undertaken. Symptoms
      of nasal obstruction were assessed using the Visual Analogue Scale (VAS) and peak
      inspiratory flow rate (PIFR). This was measured preprocedure and repeated at 3,
      6, and 12 months postoperatively. RESULTS: A total of 35 patients were
      identified, and 26 were included in the study; 90% of patients were satisfied
      with the outcome of surgery, supported by improvement in the VAS and PIFR scores.
      The mean difference in VAS preprocedure and postprocedure was 4.97 (P value =
      0.00), and the average improvement in PIFR was 25.5 L/min (P value = 0.00).
      CONCLUSION: Our study shows a significant improvement in patient's symptoms
      following insertion of alar suspension sutures. It is, therefore, a reliable,
      safe, and effective technique in treating nasal obstruction secondary to nasal
      valve collapse.

PMID- 25991834
TI  - Defining the Morphology and Distribution of the Alar Fascia: A Sheet Plastination
      Investigation.
AB  - OBJECTIVES: This study aims to delineate the morphology, integrity, and
      distribution of the alar fascia using dissection and E12 sheet plastination. This
      is the first study that employs E12 sheet plastination to investigate the alar
      fascia and its adjacent potential spaces. METHODS: Twenty-nine manual dissections
      and 3 sets of E12 sheet plastinations were used to examine the posterior
      pharyngeal region for the architecture and distribution of the alar fascia.
      Specimens were examined from the inferior nuchal line to C6. RESULTS: The alar
      fascia originated as a well-defined midline structure at the level of C1 and
      could be identified down to C6. There was no evidence of the alar fascia between
      the inferior nuchal line and the base of the skull. Notably, the alar fascia
      permitted resistance to manual traction. CONCLUSIONS: E12 sheet plastination
      allowed for visualization of the alar fascia's superior attachments within the
      deep cervical region. Resistance to traction suggests that the alar fascia may be
      more than just a loose fibroareolar matrix. The findings in this study suggest an
      alternative point of entry into the danger space. Understanding the continuity of
      this fascial layer is critically important with regard to the pathophysiology of
      deep neck space infections.

PMID- 25991835
TI  - Treatment Selection for T3/T4a Laryngeal Cancer: Chemoradiation Versus Primary
      Surgery.
AB  - OBJECTIVE: We report the treatment outcomes, including organ preservation, for
      patients with locally advanced (T3/T4a) laryngeal cancer receiving both surgical
      and nonsurgical approaches. We hypothesize that selection of treatment protocols
      aimed to optimize organ preservation does not compromise survival provided
      careful selection is done through the process of multidisciplinary treatment
      planning. METHODS: Patients with T3-4a laryngeal squamous cell cancer were
      evaluated and recommended for primary treatment with total or partial
      laryngectomy (37 patients) or chemoradiotherapy (34 patients). Treatment outcomes
      were compared between the 2 cohorts. In addition, the laryngeal preservation rate
      and laryngoesophageal dysfunction-free survival (LEDFS) were determined for the
      chemoradiation group. RESULTS: The 5-year overall survival rate for patients with
      T3 lesions was 41% and 40% for the surgical and nonsurgical groups, respectively,
      and for T4 lesions it was 54% and 53%, respectively. For the chemoradiation
      group, the rate of overall laryngeal preservation was 79%. LEDFS at 2 years was
      40% for T3 lesions and 33% for T4 lesions. CONCLUSION: Through careful selection,
      some patients with locally advanced laryngeal cancer can be offered
      chemoradiation (organ preservation) without compromising survival. However, the
      patients selected to receive chemoradiation have a high rate of laryngeal and
      esophageal dysfunction.

PMID- 25991837
TI  - Ensuring the security of health care in conflict settings: an urgent global
      health concern.

PMID- 25991836
TI  - The human microbiome.

PMID- 25991838
TI  - Rise in violence against doctors in Turkey, elsewhere.

PMID- 25991839
TI  - Bilateral corneal edema associated with amantadine.

PMID- 25991841
TI  - Backlash at MJA for firing another editor.

PMID- 25991840
TI  - Determinants of variations in initial treatment strategies for stable ischemic
      heart disease.
AB  - BACKGROUND: The ratio of revascularization to medical therapy (referred to herein
      as the revascularization ratio) for the initial treatment of stable ischemic
      heart disease varies considerably across hospitals. We conducted a comprehensive
      study to identify patient, physician and hospital factors associated with
      variations in the revascularization ratio across 18 cardiac centres in the
      province of Ontario. We also explored whether clinical outcomes differed between
      hospitals with high, medium and low ratios. METHODS: We identified all patients
      in Ontario who had stable ischemic heart disease documented by index angiography
      performed between Oct. 1, 2008, and Sept. 30, 2011, at any of the 18 cardiac
      centres in the province. We classified patients by initial treatment strategy
      (medical therapy or revascularization). Hospitals were classified into equal
      tertiles based on their revascularization ratio. The primary outcome was all
      cause mortality. Patient follow-up was until Dec. 31, 2012. Hierarchical logistic
      regression models identified predictors of revascularization. Multivariable Cox
      proportional hazards models, with a time-varying covariate for actual treatment
      received, were used to evaluate the impact of the revascularization ratio on
      clinical outcomes. RESULTS: Variation in revascularization ratios was twofold
      across the hospitals. Patient factors accounted for 67.4% of the variation in
      revascularization ratios. Physician and hospital factors were not significantly
      associated with the variation. Significant patient-level predictors of
      revascularization were history of smoking, multivessel disease, high-risk
      findings on noninvasive stress testing and more severe symptoms of angina (v. no
      symptoms). Treatment at hospitals with a high revascularization ratio was
      associated with increased mortality compared with treatment at hospitals with a
      low ratio (hazard ratio 1.12, 95% confidence interval 1.03-1.21). INTERPRETATION:
      Most of the variation in revascularization ratios across hospitals was warranted,
      in that it was driven by patient factors. Nonetheless, the variation was
      associated with potentially important differences in mortality.

PMID- 25991843
TI  - Fund basic research say polled Canadians.

PMID- 25991844
TI  - Health groups hunger for prompt label change.

PMID- 25991845
TI  - Screening for autism spectrum disorder in underserved communities: Early
      childcare providers as reporters.
AB  - Early diagnosis of autism typically is associated with earlier access to
      intervention and improved outcomes. Daycares and preschools largely have been
      ignored as possible venues for early identification. This may be especially
      important for minority children in the United States who are typically diagnosed
      with autism later than White children, limiting their access to early specialized
      interventions and possibly resulting in poorer outcomes. Early childcare
      providers within underserved communities completed autism screening tools for a
      sample of low-risk young children (n = 967) in their programs. Early childcare
      providers returned screening tools for 90% of the children for whom parental
      consent had been received. A total of 14% of children screened positive for
      autism spectrum disorder and 3% of the sample met criteria for autism spectrum
      disorder. Among those who screened positive, 34% were lost to follow-up. Findings
      suggest that early childcare providers can effectively screen young children for
      autism spectrum disorder in preschool/daycare settings, thus improving access to
      early diagnosis and reducing potential healthcare disparities among underserved
      populations. 

PMID- 25991846
TI  - The utility of Thin Slice ratings for predicting language growth in children with
      autism spectrum disorder.
AB  - Literature on "Thin Slice" ratings indicates that a number of personality
      characteristics and behaviors can be accurately predicted by ratings of very
      short segments (<5 min) of behavior. This study examined the utility of Thin
      Slice ratings of young children with autism spectrum disorder for predicting
      developmental skills and language gains over time. A total of 22 preschool-aged
      children with autism spectrum disorder participated in a battery of developmental
      assessments and a video-taped therapist-child interaction at Time 1. They then
      participated in follow-up testing of language skills and a second therapist-child
      interaction 6 months later (Time 2). Groups of approximately 25 naive
      undergraduate students provided impression ratings ("Thin Slice ratings") about
      each child's skills and behaviors during 2-min segments taken from the therapist
      child interaction videos at each time point. Thin Slice ratings at Time 1 were
      highly correlated with child scores on several developmental assessments at Time
      1. In addition, Thin Slice ratings at Time 1 predicted gain in parent-reported
      expressive vocabulary over the course of 6 months, over and above the predictive
      utility of Time 1 vocabulary size. These findings provide preliminary evidence
      for the concurrent and predictive validity of Thin Slice ratings in young
      children with autism spectrum disorder. 

PMID- 25991847
TI  - Core Concept: CRISPR gene editing.

PMID- 25991850
TI  - Time to rethink EMRs.

PMID- 25991851
TI  - Cannabis every day?

PMID- 25991852
TI  - Inguinal hernia.

PMID- 25991853
TI  - Inguinal hernia.

PMID- 25991854
TI  - New oral anticoagulants.

PMID- 25991855
TI  - Mobitz II.

PMID- 25991856
TI  - VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and
      serves as a marker of poor prognosis for cancer patients.
AB  - The biological functions of VEGF-B in cancer progression remain poorly
      understood. Here, we report that VEGF-B promotes cancer metastasis through the
      remodeling of tumor microvasculature. Knockdown of VEGF-B in tumors resulted in
      increased perivascular cell coverage and impaired pulmonary metastasis of human
      melanomas. In contrast, the gain of VEGF-B function in tumors led to
      pseudonormalized tumor vasculatures that were highly leaky and poorly perfused.
      Tumors expressing high levels of VEGF-B were more metastatic, although primary
      tumor growth was largely impaired. Similarly, VEGF-B in a VEGF-A-null tumor
      resulted in attenuated primary tumor growth but substantial pulmonary metastases.
      VEGF-B also led to highly metastatic phenotypes in Vegfr1 tk(-/-) mice and mice
      treated with anti-VEGF-A. These data indicate that VEGF-B promotes cancer
      metastasis through a VEGF-A-independent mechanism. High expression levels of VEGF
      B in two large-cohort studies of human patients with lung squamous cell carcinoma
      and melanoma correlated with poor survival. Taken together, our findings
      demonstrate that VEGF-B is a vascular remodeling factor promoting cancer
      metastasis and that targeting VEGF-B may be an important therapeutic approach for
      cancer metastasis. 

PMID- 25991859
TI  - Prediction of 10-fold coordinated TiO2 and SiO2 structures at multimegabar
      pressures.
AB  - We predict by first-principles methods a phase transition in TiO2 at 6.5 Mbar
      from the Fe2P-type polymorph to a ten-coordinated structure with space group
      I4/mmm. This is the first report, to our knowledge, of the pressure-induced phase
      transition to the I4/mmm structure among all dioxide compounds. The I4/mmm
      structure was found to be up to 3.3% denser across all pressures investigated.
      Significant differences were found in the electronic properties of the two
      structures, and the metallization of TiO2 was calculated to occur concomitantly
      with the phase transition to I4/mmm. The implications of our findings were
      extended to SiO2, and an analogous Fe2P-type to I4/mmm transition was found to
      occur at 10 TPa. This is consistent with the lower-pressure phase transitions of
      TiO2, which are well-established models for the phase transitions in other AX2
      compounds, including SiO2. As in TiO2, the transition to I4/mmm corresponds to
      the metallization of SiO2. This transformation is in the pressure range reached
      in the interiors of recently discovered extrasolar planets and calls for a
      reformulation of the equations of state used to model them. 

PMID- 25991858
TI  - Avian sarcoma leukosis virus receptor-envelope system for simultaneous dissection
      of multiple neural circuits in mammalian brain.
AB  - Pathway-specific gene delivery is requisite for understanding complex neuronal
      systems in which neurons that project to different target regions are locally
      intermingled. However, conventional genetic tools cannot achieve simultaneous,
      independent gene delivery into multiple target cells with high efficiency and low
      cross-reactivity. In this study, we systematically screened all receptor-envelope
      pairs resulting from the combination of four avian sarcoma leukosis virus (ASLV)
      envelopes (EnvA, EnvB, EnvC, and EnvE) and five engineered avian-derived
      receptors (TVA950, TVB(S3), TVC, TVB(T), and DR-46TVB) in vitro. Four of the 20
      pairs exhibited both high infection rates (TVA-EnvA, 99.6%; TVB(S3)-EnvB, 97.7%;
      TVC-EnvC, 98.2%; and DR-46TVB-EnvE, 98.8%) and low cross-reactivity (<2.5%).
      Next, we tested these four receptor-envelope pairs in vivo in a pathway-specific
      gene-transfer method. Neurons projecting into a limited somatosensory area were
      labeled with each receptor by retrograde gene transfer. Three of the four pairs
      exhibited selective transduction into thalamocortical neurons expressing the
      paired receptor (>98%), with no observed cross-reaction. Finally, by expressing
      three receptor types in a single animal, we achieved pathway-specific,
      differential fluorescent labeling of three thalamic neuronal populations, each
      projecting into different somatosensory areas. Thus, we identified three
      orthogonal pairs from the list of ASLV subgroups and established a new vector
      system that provides a simultaneous, independent, and highly specific genetic
      tool for transferring genes into multiple target cells in vivo. Our approach is
      broadly applicable to pathway-specific labeling and functional analysis of
      diverse neuronal systems. 

PMID- 25991857
TI  - Regulation of age-related macular degeneration-like pathology by complement
      factor H.
AB  - Complement factor H (CFH) is a major susceptibility gene for age-related macular
      degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here,
      the role of CFH in the development of AMD pathology in vivo was interrogated by
      analyzing aged Cfh(+/-) and Cfh(-/-) mice fed a high-fat, cholesterol-enriched
      diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented
      epithelium (sub-RPE) deposit formation, specifically basal laminar deposits,
      following high-fat diet. Mechanistically, our data show that deposits are due to
      CFH competition for lipoprotein binding sites in Bruch's membrane. Interestingly
      and despite sub-RPE deposit formation occurring in both Cfh(+/-) and Cfh(-/-)
      mice, RPE damage accompanied by loss of vision occurred only in old Cfh(+/-)
      mice. We demonstrate that such pathology is a function of excess complement
      activation in Cfh(+/-) mice versus complement deficiency in Cfh(-/-) animals. Due
      to the CFH-dependent increase in sub-RPE deposit height, we interrogated the
      potential of CFH as a previously unidentified regulator of Bruch's membrane
      lipoprotein binding and show, using human Bruch's membrane explants, that CFH
      removes endogenous human lipoproteins in aged donors. Thus, advanced age, high
      fat diet, and decreased CFH induce sub-RPE deposit formation leading to
      complement activation, which contributes to RPE damage and visual function
      impairment. This new understanding of the complicated interactions of CFH in AMD
      like pathology provides an improved foundation for the development of targeted
      therapies for AMD. 

PMID- 25991860
TI  - BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.
AB  - Knowledge of the mechanisms by which a cell detects exogenous DNA is important
      for controlling pathogen infection, because most pathogens entail the presence of
      exogenous DNA in the cytosol, as well as for understanding the cell's response to
      artificially transfected DNA. The cellular response to pathogen invasion has been
      well studied. However, spatiotemporal information of the cellular response
      immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is
      lacking, in part because of difficulties in monitoring when exogenous dsDNA
      enters the cytosol of the cell. We have recently developed a method to monitor
      endosome breakdown around exogenous materials using transfection reagent-coated
      polystyrene beads incorporated into living human cells as the objective for
      microscopic observations. In the present study, using dsDNA-coated polystyrene
      beads (DNA-beads) incorporated into living cells, we show that barrier-to
      autointegration factor (BAF) bound to exogenous dsDNA immediately after its
      appearance in the cytosol at endosome breakdown. The BAF(+) DNA-beads then
      assembled a nuclear envelope (NE)-like membrane and avoided autophagy that
      targeted the remnants of the endosome membranes. Knockdown of BAF caused a
      significant decrease in the assembly of NE-like membranes and increased the
      formation of autophagic membranes around the DNA-beads, suggesting that BAF
      mediated assembly of NE-like membranes was required for the DNA-beads to evade
      autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like
      membranes and avoided autophagy. We propose a new role for BAF: remodeling
      intracellular membranes upon detection of dsDNA in mammalian cells. 

PMID- 25991863
TI  - Recognising facial onset sensory motor neuronopathy syndrome: insight from six
      new cases.
AB  - Facial onset sensory and motor neuronopathy (FOSMN) was first described in 2006
      as an apparently sporadic neurodegenerative disease. Thirty cases have been
      reported to date. We summarise six new cases, highlighting the key clinical
      aspects of FOSMN and how to differentiate it from motor neurone disease
      (amyotrophic lateral sclerosis). Typically, patients present with slowly evolving
      numbness of the face followed by bulbar and proximal (neck and arm) weakness.
      However, one of our patients presented with a motor syndrome and his abnormal
      blink reflex studies provided a useful diagnostic clue. This extends the spectrum
      of the syndrome and emphasises that FOSMN should be considered in the
      differential diagnosis of motor neurone disease. We discuss the pathophysiology,
      diagnosis, prognosis and management considerations of FOSMN. 

PMID- 25991862
TI  - Structural rearrangements in the phage head-to-tail interface during assembly and
      infection.
AB  - Many icosahedral viruses use a specialized portal vertex to control genome
      encapsidation and release from the viral capsid. In tailed bacteriophages, the
      portal system is connected to a tail structure that provides the pipeline for
      genome delivery to the host cell. We report the first, to our knowledge,
      subnanometer structures of the complete portal-phage tail interface that mimic
      the states before and after DNA release during phage infection. They uncover
      structural rearrangements associated with intimate protein-DNA interactions. The
      portal protein gp6 of bacteriophage SPP1 undergoes a concerted reorganization of
      the structural elements of its central channel during interaction with DNA. A
      network of protein-protein interactions primes consecutive binding of proteins
      gp15 and gp16 to extend and close the channel. This critical step that prevents
      genome leakage from the capsid is achieved by a previously unidentified
      allosteric mechanism: gp16 binding to two different regions of gp15 drives
      correct positioning and folding of an inner gp16 loop to interact with equivalent
      loops of the other gp16 subunits. Together, these loops build a plug that closes
      the channel. Gp16 then fastens the tail to yield the infectious virion. The
      gatekeeper system opens for viral genome exit at the beginning of infection but
      recloses afterward, suggesting a molecular diaphragm-like mechanism to control
      DNA efflux. The mechanisms described here, controlling the essential steps of
      phage genome movements during virus assembly and infection, are likely to be
      conserved among long-tailed phages, the largest group of viruses in the
      Biosphere. 

PMID- 25991861
TI  - Rapid molecular evolution across amniotes of the IIS/TOR network.
AB  - The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network
      regulates lifespan and reproduction, as well as metabolic diseases, cancer, and
      aging. Despite its vital role in health, comparative analyses of IIS/TOR have
      been limited to invertebrates and mammals. We conducted an extensive evolutionary
      analysis of the IIS/TOR network across 66 amniotes with 18 newly generated
      transcriptomes from nonavian reptiles and additional available
      genomes/transcriptomes. We uncovered rapid and extensive molecular evolution
      between reptiles (including birds) and mammals: (i) the IIS/TOR network,
      including the critical nodes insulin receptor substrate (IRS) and
      phosphatidylinositol 3-kinase (PI3K), exhibit divergent evolutionary rates
      between reptiles and mammals; (ii) compared with a proxy for the rest of the
      genome, genes of the IIS/TOR extracellular network exhibit exceptionally fast
      evolutionary rates; and (iii) signatures of positive selection and coevolution of
      the extracellular network suggest reptile- and mammal-specific interactions
      between members of the network. In reptiles, positively selected sites cluster on
      the binding surfaces of insulin-like growth factor 1 (IGF1), IGF1 receptor
      (IGF1R), and insulin receptor (INSR); whereas in mammals, positively selected
      sites clustered on the IGF2 binding surface, suggesting that these hormone
      receptor binding affinities are targets of positive selection. Further, contrary
      to reports that IGF2R binds IGF2 only in marsupial and placental mammals, we
      found positively selected sites clustered on the hormone binding surface of
      reptile IGF2R that suggest that IGF2R binds to IGF hormones in diverse taxa and
      may have evolved in reptiles. These data suggest that key IIS/TOR paralogs have
      sub- or neofunctionalized between mammals and reptiles and that this network may
      underlie fundamental life history and physiological differences between these
      amniote sister clades. 

PMID- 25991864
TI  - A fully human scFv phage display library for rapid antibody fragment
      reformatting.
AB  - Phage display libraries of human single-chain variable fragments (scFvs) are a
      reliable source of fully human antibodies for scientific and clinical
      applications. Frequently, scFvs form the basis of larger, bivalent formats to
      increase valency and avidity. A small and versatile bivalent antibody fragment is
      the diabody, a cross-paired scFv dimer (~55 kDa). However, generation of
      diabodies from selected scFvs requires decreasing the length of the interdomain
      scFv linker, typically by overlap PCR. To simplify this process, we designed two
      scFv linkers with integrated restriction sites for easy linker length reduction
      (17-residue to 7-residue or 18-residue to 5-residue, respectively) and generated
      two fully human scFv phage display libraries. The larger library (9 * 10(9)
      functional members) was employed for selection against a model antigen, human N
      cadherin, yielding novel scFv clones with low nanomolar monovalent affinities.
      ScFv clones from both libraries were reformatted into diabodies by restriction
      enzyme digestion and re-ligation. Size-exclusion chromatography analysis
      confirmed the proper dimerization of most of the diabodies. In conclusion, these
      specially designed scFv phage display libraries allow us to rapidly reformat the
      selected scFvs into diabodies, which can greatly accelerate early stage antibody
      development when bivalent fragments are needed for candidate screening. 

PMID- 25991866
TI  - Are we recording postoperative complications correctly? Comparison of NHS
      Hospital Episode Statistics with the American College of Surgeons National
      Surgical Quality Improvement Program.
AB  - BACKGROUND: Hospital Episode Statistics (HES) data are used to measure surgical
      outcomes, but its quality has been considered inferior to that of clinical
      databases. We compare the recording accuracy of HES, an administrative database
      used in the National Health Service (NHS), with that of ACS NSQIP (American
      College of Surgeons National Surgical Quality Improvement Program), a well
      established clinical database. METHODS: 1323 patient records from our hospital,
      common to both databases were compared for ten surgical procedures (amputation,
      appendicectomy, cholecystectomy, femoral hernia repair, Hartmann's procedure,
      incisional hernia repair, inguinal hernia repair, long saphenous vein surgery,
      parathyroidectomy and umbilical hernia repair) and nine postoperative
      complications (acute renal failure, myocardial infarction, pneumonia, pulmonary
      embolism, urinary tract infection, blood transfusion, septic shock, surgical site
      infection and wound disruption) using text strings or ICD-10 (International
      Classification of Diseases) codes. kappa coefficient was calculated as a measure
      of concordance between HES and ACS NSQIP databases. RESULTS: The databases showed
      perfect or very good agreement in recording a majority of surgical procedures
      (kappa coefficient range 0.82-1.0), but there was discordance in recording
      postoperative complications. When HES was investigated using text string or ICD
      10 code, the kappa coefficient range for nine postoperative complications was
      0.00-0.56, indicating poor to moderate inter-rater agreement. Concordance was
      even less when searched by HES coder's recommended way to record postoperative
      complications. CONCLUSIONS: HES poorly registers postoperative complications.
      Suggested improvements include addition of dates when a condition is diagnosed,
      agreed criteria to identify postoperative complications, specifically trained
      coding staff for surgery and consistent use of the coding guidance.

PMID- 25991867
TI  - A 'Just Culture' for performance measures.

PMID- 25991865
TI  - Studying protein fold evolution with hybrids of differently folded homologs.
AB  - To study the sequence determinants governing protein fold evolution, we generated
      hybrid sequences from two homologous proteins with 40% identity but different
      folds: Pfl 6 Cro, which has a mixed alpha + beta structure, and Xfaso 1 Cro,
      which has an all alpha-helical structure. First, we first examined eight chimeric
      hybrids in which the more structurally conserved N-terminal half of one protein
      was fused to the more structurally divergent C-terminal half of the other. None
      of these chimeras folded, as judged by circular dichroism spectra and thermal
      melts, suggesting that both halves have strong intrinsic preferences for the
      native global fold pattern, and/or that the interfaces between the halves are not
      readily interchangeable. Second, we examined 10 hybrids in which blocks of the
      structurally divergent C-terminal region were exchanged. These hybrids showed
      varying levels of thermal stability and suggested that the key residues in the
      Xfaso 1 C terminus specifying the all-alpha fold were concentrated near the end
      of helix 4 in Xfaso 1, which aligns to the end of strand 2 in Pfl 6. Finally, we
      generated hybrid substitutions for each individual residue in this critical
      region and measured thermal stabilities. The results suggested that R47 and V48
      were the strongest factors that excluded formation of the alpha + beta fold in
      the C-terminal region of Xfaso 1. In support of this idea, we found that the
      folding stability of one of the original eight chimeras could be rescued by back
      substituting these two residues. Overall, the results show not only that the key
      factors for Cro fold specificity and evolution are global and multifarious, but
      also that some all-alpha Cro proteins have a C-terminal subdomain sequence within
      a few substitutions of switching to the alpha + beta fold. 

PMID- 25991868
TI  - Quality improvement in academic medical centres: a resident perspective.

PMID- 25991869
TI  - Short-term dipeptidyl peptidase-4 inhibitor use increases the risk of herpes
      zoster infection in Asian patients with diabetes.
AB  - BACKGROUND: We aimed to evaluate whether patients with diabetes who use
      dipeptidyl peptidase (DPP)-4 inhibitors are at a higher risk of developing a
      herpes zoster (HZ) infection. METHODS: We used a subset of the Longitudinal
      Health Insurance Database 2000 containing all inpatient and outpatient medical
      claims of ~1 million people who were randomly sampled from the National Health
      Insurance Research Database. Patients who were newly diagnosed with Type 2
      diabetes International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM 250.x0 and 250.x2) who used antidiabetic medications were
      divided into two cohorts based on their use of DPP-4 inhibitors between 2009 and
      2011. Cox proportion hazard regression models were used to assess the effects of
      DPP-4 inhibitors on the incidence of HZ compared with the non-DPP-4-inhibitor
      exposed cohort. RESULTS: Patients in DPP-4-inhibitor-exposed cohort with diabetes
      and HZ infections revealed an incidence density of 4.20 per 1000 person-years
      compared with 3.50 per 1000 person-years for the non-DPP-4-inhibitor-exposed
      cohort (adjusted hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 0.70
      1.99). Furthermore, high-dose DPP-4-inhibitor treatment was associated with a
      significantly higher risk of HZ (adjusted HR = 2.46, 95% CI = 1.16-5.19 for a
      defined daily dose [DDD] >= 360). In addition, short-term DPP-4-inhibitor
      treatment was associated with a significantly higher risk of HZ (adjusted HR =
      2.04, 95% CI = 1.03-4.04 for a DDD >= 360 days). CONCLUSION: These results
      suggest that Asian patients with diabetes who use short-term DPP-4 inhibitors
      might be at a higher risk of developing HZ.

PMID- 25991871
TI  - Becker's nevus.

PMID- 25991870
TI  - Cannon ball pulmonary metastases.

PMID- 25991872
TI  - Piebaldism.

PMID- 25991874
TI  - (100)-Textured KNN-based thick film with enhanced piezoelectric property for
      intravascular ultrasound imaging.
AB  - Using tape-casting technology, 35 MUm free-standing (100)-textured Li doped KNN
      (KNLN) thick film was prepared by employing NaNbO3 (NN) as template. It exhibited
      similar piezoelectric behavior to lead containing materials: a longitudinal
      piezoelectric coefficient (d33) of ~150 pm/V and an electromechanical coupling
      coefficient (kt ) of 0.44. Based on this thick film, a 52 MHz side-looking
      miniature transducer with a bandwidth of 61.5% at -6 dB was built for
      Intravascular ultrasound (IVUS) imaging. In comparison with 40 MHz PMN-PT single
      crystal transducer, the rabbit aorta image had better resolution and higher noise
      to-signal ratio, indicating that lead-free (100)-textured KNLN thick film may be
      suitable for IVUS (>50 MHz) imaging.

PMID- 25991873
TI  - Pseudomonas aeruginosa meningitis/ventriculitis in a UK tertiary referral
      hospital.
AB  - BACKGROUND: Pseudomonas aeruginosa is a rare cause of meningitis and
      ventriculitis but is generally associated with significant morbidity and
      mortality. AIM: We sought to determine the epidemiology, risk factors and outcome
      of meningitis and ventriculitis due to P. aeruginosa at our institution in order
      to inform preventive strategies and treatment guidelines. METHODS: Retrospective
      study of all patients with a positive cerebrospinal fluid (CSF) culture admitted
      to a tertiary care hospital over 18 years. Clinical details, demographic,
      microbiological and antibiotic data were obtained from laboratory and medical
      records. RESULTS: Twenty-four episodes occurred in 21 patients over 18 years.
      Pyrexia (75%), fluctuating mental status (50%) and headache (41%) were the most
      frequent presenting symptoms. Nineteen of the 21 patients had previously
      undergone a neurosurgical procedure and seven had extra-ventricular devices in
      situ. Twelve (57%) patients had P. aeruginosa isolated from another site prior to
      their episode. Most (89%) CSF samples demonstrated a neutrophilia; the CSF
      protein, when measured, was raised in all cases. Gram-negative bacilli were
      visible on CSF microscopy in only three isolates. There were relatively low rates
      of resistance to most antimicrobials tested and combination treatment of
      intravenous with intrathecal antibiotics was often used. No patients died within
      28 days. CONCLUSION: Pseudomonas aeruginosa meningitis and ventriculitis are
      predominantly nosocomial and related to prior neurosurgery. It can be difficult
      to diagnose as CSF Gram-film and meningism are insensitive markers. Appropriate
      empirical treatment, neurosurgical prophylaxis and surveillance can aid in
      managing this infection.

PMID- 25991875
TI  - Reconstruction of magnetic domain structure using the reverse Monte Carlo method
      with an extended Fourier image.
AB  - Visualization of the magnetic domain structure is indispensable to the
      investigation of magnetization processes and the coercivity mechanism. It is
      necessary to develop a reconstruction method from the reciprocal-space image to
      the real-space image. For this purpose, it is necessary to solve the problem of
      missing phase information in the reciprocal-space image. We propose the method of
      extend Fourier image with mean-value padding to compensate for the phase
      information. We visualized the magnetic domain structure using the Reverse Monte
      Carlo method with simulated annealing to accelerate the calculation. With this
      technique, we demonstrated the restoration of the magnetic domain structure,
      obtained magnetization and magnetic domain width, and reproduced the
      characteristic form that constitutes a magnetic domain.

PMID- 25991876
TI  - Rendering-Based Video-CT Registration with Physical Constraints for Image-Guided
      Endoscopic Sinus Surgery.
AB  - We present a system for registering the coordinate frame of an endoscope to pre-
      or intra- operatively acquired CT data based on optimizing the similarity metric
      between an endoscopic image and an image predicted via rendering of CT. Our
      method is robust and semi-automatic because it takes account of physical
      constraints, specifically, collisions between the endoscope and the anatomy, to
      initialize and constrain the search. The proposed optimization method is based on
      a stochastic optimization algorithm that evaluates a large number of similarity
      metric functions in parallel on a graphics processing unit. Images from a cadaver
      and a patient were used for evaluation. The registration error was 0.83 mm and
      1.97 mm for cadaver and patient images respectively. The average registration
      time for 60 trials was 4.4 seconds. The patient study demonstrated robustness of
      the proposed algorithm against a moderate anatomical deformation.

PMID- 25991877
TI  - Moving ahead.

PMID- 25991878
TI  - Dr. Suresh Raghunath Tambwekar: A man with a vision.

PMID- 25991879
TI  - Pressure ulcers: Current understanding and newer modalities of treatment.
AB  - This article reviews the mechanism, symptoms, causes, severity, diagnosis,
      prevention and present recommendations for surgical as well as non-surgical
      management of pressure ulcers. Particular focus has been placed on the current
      understandings and the newer modalities for the treatment of pressure ulcers. The
      paper also covers the role of nutrition and pressure-release devices such as
      cushions and mattresses as a part of the treatment algorithm for preventing and
      quick healing process of these wounds. Pressure ulcers develop primarily from
      pressure and shear; are progressive in nature and most frequently found in
      bedridden, chair bound or immobile people. They often develop in people who have
      been hospitalised for a long time generally for a different problem and increase
      the overall time as well as cost of hospitalisation that have detrimental effects
      on patient's quality of life. Loss of sensation compounds the problem manifold,
      and failure of reactive hyperaemia cycle of the pressure prone area remains the
      most important aetiopathology. Pressure ulcers are largely preventable in nature,
      and their management depends on their severity. The available literature about
      severity of pressure ulcers, their classification and medical care protocols have
      been described in this paper. The present treatment options include various
      approaches of cleaning the wound, debridement, optimised dressings, role of
      antibiotics and reconstructive surgery. The newer treatment options such as
      negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have
      been discussed, and the advantages and disadvantages of current and newer methods
      have also been described. 

PMID- 25991880
TI  - Anatomical study of anterior supramalleolar artery and its potential application
      to design a bi-foliate fasciocutaneous flap.
AB  - PURPOSE: A further understanding of the anterior supramalleolar artery (ASMA) and
      its potential applications in reconstructive surgery. MATERIALS AND METHODS: A
      total of 24 fresh lower limbs from fresh cadavers were injected with red latex
      for dissection. The type of origin, course, diameter of the pedicle, and the
      distance between the origin of the ASMA from the anterior tibial artery to the
      extensor retinaculum (O-R) were recorded. Bi-foliate fasciocutaneous flaps were
      harvested using the branches of the ASMA. RESULTS: We found four types of origin
      of the ASMA, and we have accordingly classified them into four types. 10 of them
      were type A, 7 were type B, 6 were type C and 1 was type D. The mean O-R (origin
      of ASMA to retinaculum) distance was 2.0 +/- 0.8 cm. The diameter of the medial
      branch (D1), the diameter of the lateral branch (D2), and the diameter of artery
      stem (D3) (only in type A) were 1.0 +/- 0.2 mm, 0.8 +/- 0.3 mm, 1.1 +/- 0.2 mm,
      respectively. The mean pedicle length of the lateral flap (L1) and medial flap
      (L2) were 5.1 +/- 1.0 cm and 3.7 +/- 0.6 cm, respectively. CONCLUSIONS: The ASMA
      exists constantly with four different types of origin. Its sizable diameter and
      lengthy pedicle make it suitable for bi-foliate fasciocutaneous flap transfer.

PMID- 25991881
TI  - Effects of limited access dressing in chronic wounds: A biochemical and
      histological study.
AB  - BACKGROUND: Negative pressure wound therapy has emerged as an attractive
      treatment modality for the management and healing of chronic ulcers. Though
      numerous clinical studies are available, there is a lack of biochemical and
      histological studies evaluating the healing of chronic wounds. MATERIALS AND
      METHODS: In the present study, a total 60 patients were divided into two groups:
      Limited access dressing (LAD) group (n = 30) and conventional dressing group (n =
      30). Various biochemical parameters such as hydroxyproline, total protein and
      antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx),
      catalase (CAT) and oxidative biomarker malondialdhyde (MDA) are measured in the
      granulation tissue. Histologically amount of inflammatory infiltrate,
      angiogenesis, and collagen deposition are studied to assess wound healing.
      RESULTS: Patients treated with LAD have shown significant increase in the mean
      (+/-standard deviation) hydroxyproline (77.3 +/- 30.1 vs. 32.3 +/- 16.18; P =
      0.026), total protein (13.89 +/- 9.0 vs. 8.9 +/- 4.59; P = 0.004), GSH (7.4 +/-
      1.91 vs. 5.1 +/- 1.28; P = 0.039), GPx (122.3 +/- 59.3 vs. 88.7 +/- 34.11; P =
      0.030), CAT (1.80 +/- 1.14 vs. 0.9 +/- 0.71; P = 0.002) and decrease in MDA (13.4
      +/- 5.5 vs. 8.6 +/- 3.8; P = 0.004). Histological study showed comparatively
      fewer inflammatory cells, increased and well organised collagen bundles, and more
      angiogenesis in the LAD group when compared with that with conventional dressing
      after 10 days of treatment. CONCLUSION: In the present study, we have found
      beneficial effect of newer intermittent negative pressure therapy in combination
      with moist environment (LAD) on chronic wound healing by increasing collagen
      deposition and angiogenesis; and reducing oxidative stress and inflammatory
      infiltrate.

PMID- 25991882
TI  - Biochemical and histological study of granulation tissue to evaluate the effect
      of limited access dressing in chronic wounds: A comparative study.

PMID- 25991883
TI  - A new paradigm in facial reanimation for long-standing palsies?
AB  - BACKGROUND: A chance observation of return of excellent facial movement, after 18
      months following the first stage of cross-face nerve grafting, without free
      functional muscle transfer, in a case of long-standing facial palsy, lead the
      senior author (RBA) to further investigate clinically. PATIENTS AND METHODS: This
      procedure, now christened as cross-face nerve extension and neurotization, was
      carried out in 12 patients of very long-standing facial palsy (mean 21 years) in
      years 1996-2011. The mean patient age and duration of palsy were 30.58 years and
      21.08 years, respectively. In patients, 1-5 a single buccal or zygomatic branch
      served as a donor nerve, but subsequently, we used two donor nerves. The mean
      follow-up period was 20.75 months. RESULTS: Successive patients had excellent to
      good return of facial expression with two fair results. Besides improved smile,
      patients could largely retain air in the mouth without any escape and had
      improved mastication. No complications were encountered except synkinesis in 1
      patient. No additional surgical procedures were performed. CONCLUSION: There is
      experimental evidence to suggest that neurotization of a completely denervated
      muscle can occur by the formation of new ectopic motor end plates. Long-standing
      denervated muscle fibres eventually atrophy severely but are capable of re
      innervation and regeneration, as validated by electron microscopic studies. In
      spite of several suggestions in the literature to clinically validate functional
      recovery by direct neurotization, the concept remains anecdotal. Our results
      substantiate this procedure, and it has the potential to simplify reanimation in
      longstanding facial palsy. Our work now needs validation by other investigators
      in the field of restoring facial animation.

PMID- 25991884
TI  - Utility of arteriovenous loops before free tissue transfer for post-traumatic leg
      defects.
AB  - Crush injuries of severe magnitude involving lower limbs require complex bone and
      soft tissue reconstructions in the form of microvascular free tissue transfers.
      However, satisfactory recipient vessels are often unavailable in the leg due to
      their vulnerability to trauma and post traumatic vessel disease (PTVD), which
      extends well beyond the site of original injury. In such situations, healthy
      recipient vessels for free flap anastomosis can be made available by constructing
      temporary arteriovenous loops with saphenous vein grafts, anastomosed to
      corresponding free flap vessels. Our study included 7 patients with severe crush
      injuries of leg due to rail and road traffic accidents. Long and short saphenous
      vein grafts were anastomosed to Femoral artery in the subsartorial canal in 2
      cases and to large muscular branches and accompanying veins in rest of the cases.
      Free flap transfers were performed in the same sitting in 6 cases. One case
      showed insufficient dilatation of the vein loop and hence free flap transfer was
      staged. Free Latissimus dorsi, Gracilis and Rectus abdominis flaps were
      performed. There were two cases of flap necrosis - one in the case of a
      pathologic vein graft with staged flap transfer which showed vein thrombosis on
      re exploration. The other case of flap failure was caused by a hematoma
      underneath the flap. In another patient, secondary haemorrhage occurred on day
      18, without any consequence to the flap. All the other cases had complete free
      flap survival. We consider the use of single stage arteriovenous loops, a
      valuable tool to increase the applications of free flap, whenever healthy
      recipient vessels are not available in the periphery of the trauma. 

PMID- 25991885
TI  - Anatomic basis for an algorithmic approach for free fibula flap donor side
      selection in composite oro-mandibular defects.
AB  - INTRODUCTION: Head and neck oncological resections may result in composite oro
      mandibular defects involving the oral mucosa (lining), mandibular bone and the
      skin (cover). Reconstructive options for such defects have evolved over a period.
      Free fibula flap reconstruction is currently accepted the world over as the gold
      standard for oro-mandibular defect reconstruction. Existing literature provides
      conflicting views about the use of a particular side and orientation of the
      fibula flap for achieving the optimal outcome. The purpose of this study is to
      confirm anatomically the effect of bone, soft tissue and vessel orientation on
      the ease of doing reconstruction. MATERIALS AND METHODS: This is a cadaveric
      study. A mandibular model with a defect was used. This was pre plated to maintain
      continuity. Composite fibula flaps of the same dimension were harvested from both
      legs of a fresh cadaver. The harvested flaps were used to reconstruct the
      mandibular defect in different orientations and the best configuration for each
      reconstructive requirement was assessed. RESULTS: Keeping the peroneal surface
      for plating, that is, facing outwards, four different configurations of the
      fibula flap are possible for a given mandibular defect. With a posterior vascular
      pedicle ipsilateral fibula is suitable for skin cover and contralateral for
      mucosal lining and the reverse for an anteriorly placed pedicle. CONCLUSION: The
      algorithm based selection of appropriate sided fibula flap facilitates complex
      mandibular reconstruction by placing the right kind of tissue at the right place
      and helps in reducing the donor site morbidity by allowing the surgeon to harvest
      only the required amount of skin.

PMID- 25991886
TI  - Comparative study of Mirs(') (Mushtaq and Shabir) technique of prepuce preserving
      minimally invasive urethroplasty with Snodgrass urethroplasty for repair of
      distal hypospadias without chordee...A prospective study.
AB  - BACKGROUND: There is no single, universally applicable technique for hypospadias
      repair and numerous techniques have been practised from time to time. We compare
      the results of our new technique (Mirs' technique also called Mush & Shab's
      technique) to Snodgross urethroplasty. Mirs' technique is a modified version of
      Thiersch-Duplay urethroplasty. MATERIAL AND METHODS: This prospective comparative
      study was carried out in a tertiary care hospital of Northern India over a period
      of 3 years from March 2010 to March 2013 and included 120 patients of anterior
      (distal penile, subcoronal, coronal and glanular) hypospadias without chordee.
      They underwent either Mirs' technique (group 1 n = 60) or Snodgrass technique
      (group 2 n = 60). Follow-up was at 1-week, 1-month, 3 months and 6 months.
      RESULTS: The mean operative time was 55 min (range: 43-70 min) in group 1 and
      71.9 min (range: 60-81 min) in group 2 (P < 0.001). Urethrocutaneous fistula
      developed in two and four patients in group 1 and 2, respectively. Fistula
      closure was done at least 3 months postoperatively, and there was no significant
      difference in success rate between the two groups. Three cases of glanular
      dehiscence were detected (one in group 1 and two in group 2); the patient from
      group 1 had a successful repair using the already preserved prepuce. CONCLUSION:
      Mirs' modification of Thiersch-Duplay technique for distal hypospadias is a time
      saving procedure with a lower overall complication rate. Valuable local tissue is
      preserved to deal with any complication that may occur. Analgesic requirement was
      significantly lower in this minimally traumatic technique. As it is less time
      consuming, simple and easy to learn with a short learning curve, this technique
      deserves application in cases of distal hypospadias.

PMID- 25991887
TI  - Innovative technique: Distal venous cannulation for salvaging free flap venous
      thrombosis by heparinised saline irrigation.
AB  - INTRODUCTION: Successful free tissue transfer depends on a multitude of factors,
      and adequate drainage of venous blood is one of the most critical part of
      successful free tissue transfers. MATERIAL AND METHODS: We report 6 cases of
      microvascular free flaps used for covering various defects, which developed
      venous congestion, that were salvaged with heparinised saline irrigation through
      the distal end of the congested vein by the help of an intravenous cannula. The
      irrigation was continued for 5 days. RESULTS: All the flaps were successfully
      salvaged. CONCLUSION: This method has potential applications in situations for
      successful salvage of free tissue transfer particularly due to venous thrombosis.

PMID- 25991888
TI  - Role of platelet-rich plasma in chronic alopecia areata: Our centre experience.
AB  - AIM: The aim of the study was to evaluate the efficacy of platelet-rich plasma
      (PRP) in the treatment of chronic alopecia areata (AA). MATERIAL AND METHODS:
      This is a prospective study that was conducted at Kamal Hospital, Kaushambi in
      which 20 patients who attended the outpatient department were enrolled for the
      study. All the patients had h/o patches and taken various line of treatments for
      a duration of 2 years. All the patients were biopsy-proven positive for AA
      disease. There was no randomisation done since all of them were healthy young
      adults. The patients'age ranged from 25 to 35 years, and none of them had any co
      morbidities. RESULTS: Of 20 patients, only one patient had a relapse. None of the
      patients had any side effects, and all of them tolerated the procedure well.
      CONCLUSION: We wish to conclude that PRP has a definite role in treating AA
      infections. However, still more long-term follow-up, studies are required for
      further validation of results and labelling it as a 100% cure for people
      suffering from AA with recurrences which are so common.

PMID- 25991889
TI  - A review of 48 patients after bear attacks in Central India: Demographics,
      management and outcomes.
AB  - INTRODUCTION: Bear attacks though relatively rare are frequent enough to be of
      concern for those who are in bear habitats. Our centre at Nagpur, being
      surrounded by dense forests from all the sides, treats a large number of victims.
      AIM: The aim was to document the injuries, management and the potential
      complications of bear attacks. MATERIALS AND METHODS: We reviewed the records of
      48 consecutive patients who were treated in our department from January 2006 to
      December 2013 for bear attacks. OUTCOME: The majority of patients were referred
      24-48 h post-attack. All but two patients had involvement of either the face or
      scalp. Involvement of eyes, mandible, facial nerve, was common. Reconstruction
      included simple suture of lacerations to management of complex compound injuries
      with three-dimensional defects. Thirteen patients developed infection.
      CONCLUSION: Bear attack victims need a multidisciplinary approach. Early broad
      spectrum antibiotics, anti-rabies prophylaxis and irrigation and debridement of
      the wound are needed. We advise early referral to tertiary treatment centres.

PMID- 25991890
TI  - Smart apps for the smart plastic surgeon.
AB  - Smartphones have the ability to benefit plastic surgeons in all aspects of
      patient care and education. With the sheer number of applications available and
      more being created everyday, it is easy to miss out on apps which could be of
      great relevance. Moreover, the range of android applications available has not
      been extensively discussed in the literature. To this end, we have compiled an
      exhaustive list of android smartphone applications, which we feel can help our
      day to day functioning. The apps have been extensively reviewed and neatly
      described along with all their potential uses. In addition, we have made an
      effort to highlight 'non-medical' or efficiency apps which can improve
      departmental functioning. These apps have not been described in prior articles,
      and their functionality might not be known to all. We believe that the technology
      savvy plastic surgeon can make maximum use of these apps to his benefit. 

PMID- 25991891
TI  - A simple and rapid method of repeated tie over dressing.
AB  - Tie overdressing is commonly used to secure the graft against the raw surface and
      prevent loss due to of hematoma or seroma. A conventional tie over dressing with
      silk sutures, is a useful method of securing the graft to raw area. Refixation is
      difficult when repeated tie over dressings are needed. We assessed a low cost
      repeated tie over dressing method using sterile sample collection containers and
      silk suture threads in eight patients. After the graft is applied on the bed, tie
      over stitches are taken, and paraffin gauze is applied over with adequate
      padding; the tie over sutures are passed through the container and the lid is
      tightened over it to complete the dressing. The lid can be unscrewed easily at
      any time to inspect the graft and can be easily reapplied in the outpatient
      department. The skin graft take in all the patients was complete without any
      seroma or hematoma. A novel and low-cost tie over dressing that enables simple
      fixation of the dressing, to maintain proper position of grafts that require
      repeated fixation is reported here. 

PMID- 25991892
TI  - A novel and innovative technique of using a disposable syringe and mesh for
      harvesting fat for structural fat grafting.
AB  - BACKGROUND: Successful restoration of structure and function using autologous
      free fat grafts has remained elusive. Review of literature shows that various
      harvesting and preparation techniques have been suggested. The goal of these
      techniques is to obtain greater adipocyte cell survival and consequently more
      reliable clinical results. MATERIALS AND METHODS: In our technique, a piece of
      mesh is kept at one end of the lipoaspiration syringe, which is then connected to
      the Suction pump. As one syringe fills, it is replaced by another one until the
      required amount of fat is obtained. RESULTS: By using a polypropylene mesh in our
      technique, we can separate the transfusate from the harvested fat graft during
      harvesting itself. The fat graft thus obtained is dense and concentrated, with
      fewer impurities. CONCLUSION: Hence, we recommend our technique as a reliable
      method for extracting sterile emulsified fat in an economical way.

PMID- 25991893
TI  - Successful pregnancy "during" pedicled transverse rectus abdominis
      musculocutaneous flap for breast reconstruction with normal vaginal delivery.
AB  - A transverse rectus abdominis myocutaneous (TRAM) flap is a popular choice for
      breast reconstruction. Pregnancies in women following a TRAM flap present
      concerns regarding both safety and the integrity of the abdominal wall. We report
      a case of a patient who was pregnant during immediate breast reconstruction with
      pedicled TRAM flap and had a successful spontaneous vaginal delivery. We also
      conducted a literature review using PubMed on pregnancy post TRAM flap, type of
      reconstruction, timing of pregnancy after TRAM flap, complication, and mode of
      delivery, which are summarised in this report. We concluded that patients may
      have safe pregnancies and normal deliveries following TRAM flap breast
      reconstruction regardless of the time frame of pregnancy after the procedure.
      Therefore, TRAM flaps can continue to be a reconstruction option, even in women
      of childbearing age. 

PMID- 25991894
TI  - Revision breast and chest wall reconstruction in Poland and pectus excavatum
      following implant complication using free deep inferior epigastric perforator
      flap.
AB  - This study aims to present the case of a female patient with Poland's syndrome
      and pectus excavatum deformity who underwent breast and chest wall reconstruction
      with a pre-shaped free deep inferior epigastric perforator flap. A 57-year-old
      female patient with Poland's syndrome and pectus excavatum presented with a Baker
      III capsular contracture following a previously performed implant-based right
      breast reconstruction. After a chest and abdominal CT angiography, she was staged
      as 2A1 chest wall deformity according to Park's classification and underwent
      implant removal and capsulectomy, followed by a pre-shaped free abdominal flap
      transfer, providing both breast reconstruction and chest wall deformity
      correction in a single stage operation. Post-operative course was uneventful, and
      the aesthetic result remains highly satisfactory 24 months after surgery. Deep
      inferior epigastric free flap represents an interesting reconstructive solution
      when treating Poland's syndrome female patients with chest wall and breast
      deformities. 

PMID- 25991895
TI  - Management of post midface distraction occlusal discrepancy using temporary
      anchorage devices in a cleft patient.
AB  - Open bite deformity following a successful midface advancement by distraction
      osteogenesis is a common complication. Temporary anchorage devices can be
      deployed during the distraction and post-distraction settling phases for
      restoring the occlusion even in severe cases. The following report describes the
      management of severe anterior open bite following maxillary distraction. 

PMID- 25991896
TI  - Parotid duct cyst in a child.

PMID- 25991897
TI  - A simple and safe penile tourniquet.

PMID- 25991898
TI  - Peroneal muscle eversion technique for fibula flap.

PMID- 25991899
TI  - A novel method of marking nipple areola complex in gynaecomastia surgery.

PMID- 25991900
TI  - Simple ways to improve undergraduate plastic surgery education.

PMID- 25991901
TI  - Diverse classification systems for maxillectomy defects: Simplifying or
      complicating the treatment plan?

PMID- 25991902
TI  - A different perspective for creating fistula.

PMID- 25991903
TI  - Reply to the letter to editor.

PMID- 25991904
TI  - The ulnar digital artery perforator flaps.

PMID- 25991905
TI  - A novel wiring technique in mandibular condylar fracture: customised interdental
      wire hooks.

PMID- 25991906
TI  - Anatomical variation of superficial radial nerve during free radial forearm flap
      harvest.

PMID- 25991907
TI  - An alternative means of retaining ocular structure and improving immunoreactivity
      for light microscopy studies.
AB  - PURPOSE: Several properties of ocular tissue make fixation for light microscopy
      problematic. Because the eye is spherical, immersion fixation necessarily results
      in a temporal gradient of fixation, with surfaces fixing more rapidly and
      thoroughly than interior structures. The problem is compounded by the fact that
      the layers of the eye wall are compositionally quite different, resulting in
      different degrees of fixation-induced shrinkage and distortion. Collectively,
      these result in non-uniform preservation, as well as buckling and/or retinal
      detachment. This gradient problem is most acute for the lens, where the density
      of proteins can delay fixation of the central lens for days, and where the
      fixation gradient parallels the age gradient of lens cells, which complicates
      data interpretation. Our goal was to identify a simple method for minimizing some
      of the problems arising from immersion fixation, which avoided covalent
      modification of antigens, retained high quality structure, and maintained tissue
      in a state that is amenable to common cytochemical techniques. METHODS: A simple
      and inexpensive derivative of the freeze-substitution approach was developed and
      compared to fixation by immersion in formalin. Preservation of structure,
      immunoreactivity, GFP and tdTomato fluorescence, lectin reactivity, outer segment
      auto fluorescence, Click-iT chemistry, compatibility with in situ hybdrdization,
      and the ability to rehydrate eyes after fixation by freeze substitution for
      subsequent cryo sectioning were assessed. RESULTS: An inexpensive and simple
      variant of the freeze substitution approach provides excellent structural
      preservation for light microscopy, and essentially eliminates ocular buckling,
      retinal detachment, and outer segment auto-fluorescence, without covalent
      modification of tissue antigens. The approach shows a notable improvement in
      preservation of immunoreactivity. TdTomato intrinsic fluorescence is also
      preserved, as is compatibility with in situ hybridization, lectin labeling, and
      the Click-iT chemistry approach to labeling the thymidine analog EdU. On the
      negative side, this approach dramatically reduced intrinsic GFP fluorescence.
      CONCLUSIONS: A simple, cost-effective derivative of the freeze substitution
      process is described that is of particular value in the study of rodent or other
      small eyes, where fixation gradients, globe buckling, retinal detachment,
      differential shrinkage, autofluorescence, and tissue immunoreactivity have been
      problematic.

PMID- 25991908
TI  - RNA-Seq and Network Analysis Revealed Interacting Pathways in TGF-beta-Treated
      Lung Cancer Cell Lines.
AB  - Whole transcriptome shotgun sequencing (RNA-Seq) is a useful tool for analyzing
      the transcriptome of a biological sample. With appropriate statistical and
      bioinformatic processing, this platform is capable of identifying significant
      differences in gene expression within the transcriptome and permits pathway and
      network analyses to determine how these genes interact biologically. In this
      study, we examined gene expression in two lung adenocarcinoma cell lines (H358
      and A459) that were treated with transforming growth factor-beta (TGF-beta) as a
      model for induction of the epithelial-to-mesenchymal transition (EMT), commonly
      associated with disease progression. We performed this study in order to
      illustrate a workflow for identifying interesting genes and processes that are
      regulated early in EMT and to determine their gene pathway/network relationships
      and regulation. With this, we identified 137 upregulated and 32 downregulated
      genes common to both cell lines after TGF-beta treatment that represent
      components of multiple canonical pathways and biological networks associated with
      the induction of EMT. These findings were also verified against reposited
      Affymetrix U133a expression profiles from multiple trials examining metastatic
      progression in patient cohorts (n = 731 total) to further establish the clinical
      relevance and translational significance of the model system. Together, these
      findings help validate the relevance of the TGF-beta model for the study of EMT
      and provide new insights into early events in EMT. 

PMID- 25991910
TI  - The influences of nursing transformational leadership style on the quality of
      nurses' working lives in Taiwan: a cross-sectional quantitative study.
AB  - BACKGROUND: Taiwan's NHI system is one of the most successful health care models
      for countries around the globe. However, little research has demonstrated the
      mental health issues associated with nursing transformational leadership style
      under the NHI system, especially in the quality of nurses' working lives in
      Taiwan. It is important to know the relationship between transformational
      leadership style and the mental health of nurses, organisational commitment and
      job satisfaction. The research aimed to understand the influences of nursing
      transformational leadership style on the quality of nurses' working lives in
      Taiwan. The research hypothesis was that transformational leadership styles would
      have positive influence on the quality of nurses' working lives. METHODS: This
      was a cross-sectional quantitative study. Nurses from each type of hospital
      ownership (private, public and religious) were recruited. Participation was
      voluntary and signed informed consent was obtained. The inclusion criteria were
      nurses with at least one year's work experience in the hospitals. Self
      administrated questionnaires were used. A total of 807 participants were
      contacted and 651 questionnaires were fully completed (response rate 80.7 %). A
      theory driven model was used to test the research hypotheses using structural
      equation modelling performed with AMOS 16.0. RESULTS: Transformational leadership
      contributes significantly to supervisor support. Workplace support, particularly
      from the supervisor, is an important mediator variable that explains the
      relationship between transformational leadership and job satisfaction.
      Organisational commitment was the strongest factor relevant to the general health
      well-being in Taiwanese nurses than job satisfaction. The hypothesized positive
      relationships between transformational leadership and all variables were
      supported by the data. CONCLUSIONS: Our findings have important consequences for
      organisational health. Our model demonstrates a complete picture of the work
      relationships on the quality of nurses' working lives. The results provided
      information about the subordinates' perceptions of transformational nursing
      leadership styles and mental health outcomes in different hospital settings, as
      well as identified organisational factors that could improve the quality of
      nurses' working lives.

PMID- 25991911
TI  - Inflammasomes are important mediators of prostatic inflammation associated with
      BPH.
AB  - BACKGROUND: There is mounting evidence to support the role of inflammation in
      benign prostate hyperplasia (BPH), and a recent study reported expression of
      inflammasome derived cytokine IL-18 in prostate biopsy of BPH patients. Here we
      examined the expression of inflammasome-derived cytokines and activation of
      nucleotide-binding oligomerization domain-like receptor with pyrin domain protein
      1 (NLRP) 1 inflammasome in a rat model of prostatic inflammation relevant to BPH.
      METHODS: Prostatic inflammation was experimentally induced in three-month-old
      male Sprague-Dawley rats by intraprostatic injection (50 MUL) of either 5 %
      formalin or saline (sham) into the ventral lobes of prostate. 7 days later,
      prostate and bladder tissue was harvested for analysis of inflammasome by Western
      blot, immunohistochemistry and downstream cytokine production by Milliplex.
      RESULTS: Expression of interleukins, CXC and CC chemokines were elevated 2-15
      fold in formalin injected prostate relative to sham. Significant expression of
      NLRP1 inflammasome components and caspase-1 in prostate were associated with
      significant elevation of pro and cleaved forms of IL-1beta (25.50 +/- 1.16 vs
      3.05 +/- 0.65 pg/mg of protein) and IL-18 (1646.15 +/- 182.61 vs 304.67 +/-
      103.95 pg/mg of protein). Relative to prostate tissue, the cytokine expression in
      bladder tissue was much lower and did not involve inflammasome activation.
      CONCLUSIONS: Significant upregulation of NLRP1, caspase-1 and downstream
      cytokines (IL-18 and IL-1beta) suggests that a NLRP1 inflammasome is assembled
      and activated in prostate tissue of this rat model . Recapitulation of findings
      from human BPH specimens suggests that the inflammasome may perpetuate the
      inflammatory state associated with BPH. Further clarification of these pathways
      may offer innovative therapeutic targets for BPH-related inflammation.

PMID- 25991912
TI  - Atrazine adsorption removal with nylon6/polypyrrole core-shell nanofibers mat:
      possible mechanism and characteristics.
AB  - A functionalized nylon6/polypyrrole core-shell nanofibers mat (PA6/PPy NFM) was
      prepared via situ polymerization on nylon6 electrospun nanofibers mat (PA6 NFM)
      template and used as an adsorbent to remove atrazine from aqueous solutions. The
      core-shell structure of PA6/PPy NFM can be clearly proved under scanning electron
      microscope (SEM), transmission electron microscopy (TEM), and X-ray photoelectron
      spectroscopy (XPS). The effects of initial solution pH and ionic strength, as
      well as the comparison of the adsorption capacity of functionalized (PA6/PPy NFM)
      and non-functionalized (PA6 NFM) adsorbent, were examined to reveal the possible
      adsorption mechanism. The results indicated that pi-pi interaction and
      electrostatic interaction should play a key role in the adsorption process. The
      kinetics and thermodynamics studies also further elucidated the detailed
      adsorption characteristics of atrazine removal by PA6/PPy NFM. The adsorption of
      atrazine could be well described by the pseudo-second-order equation. The
      adsorption equilibrium data was well fitted with the Freundlich isotherm model
      with a maximum adsorption capacity value of 14.8 mg/g. In addition, the increase
      of adsorption rate caused by a temperature increase could be felicitously
      explained by the endothermic reaction. The desorption results showed that the
      adsorption capacity remained almost unchanged after six adsorption/desorption
      cycles. These results suggest that PA6/PPy NFM could be employed as an efficient
      adsorbent for removing atrazine from contaminated water sources. 

PMID- 25991909
TI  - Expression of polarity genes in human cancer.
AB  - Polarity protein complexes are crucial for epithelial apical-basal polarity and
      directed cell migration. Since alterations of these processes are common in
      cancer, polarity proteins have been proposed to function as tumor suppressors or
      oncogenic promoters. Here, we review the current understanding of polarity
      protein functions in epithelial homeostasis, as well as tumor formation and
      progression. As most previous studies focused on the function of single polarity
      proteins in simplified model systems, we used a genomics approach to
      systematically examine and identify the expression profiles of polarity genes in
      human cancer. The expression profiles of polarity genes were distinct in
      different human tissues and classified cancer types. Additionally, polarity
      expression profiles correlated with disease progression and aggressiveness, as
      well as with identified cancer types, where specific polarity genes were commonly
      altered. In the case of Scribble, gene expression analysis indicated its common
      amplification and upregulation in human cancer, suggesting a tumor promoting
      function. 

PMID- 25991913
TI  - Nanosized zeolites as a perspective material for conductometric biosensors
      creation.
AB  - In this work, the method of enzyme adsorption on different zeolites and
      mesoporous silica spheres (MSS) was investigated for the creation of
      conductometric biosensors. The conductometric transducers consisted of gold
      interdigitated electrodes were placed on the ceramic support. The transducers
      were modified with zeolites and MSS, and then the enzymes were adsorbed on the
      transducer surface. Different methods of zeolite attachment to the transducer
      surface were used; drop coating with heating to 200 degrees C turned out to be
      the best one. Nanozeolites beta and L, zeolite L, MSS, and silicalite-1 (80 to
      450 nm) were tested as the adsorbents for enzyme urease. The biosensors with all
      tested particles except zeolite L had good analytical characteristics. Silicalite
      1 (450 nm) was also used for adsorption of glucose oxidase, acetylcholinesterase,
      and butyrylcholinesterase. The glucose and acetylcholine biosensors were
      successfully created, whereas butyrylcholinesterase was not adsorbed on
      silicalite-1. The enzyme adsorption on zeolites and MSS is simple, quick, well
      reproducible, does not require use of toxic compounds, and therefore can be
      recommended for the development of biosensors when these advantages are
      especially important. 

PMID- 25991915
TI  - Plasmonic circular resonators for refractive index sensors and filters.
AB  - A plasmonic refractive index sensor based on a circular resonator is proposed.
      With all three dimensions below 1 MUm, the sensor has a compact and simple
      structure granting it ease-of-fabrication and ease-of-use. It is capable of
      sensing trace amounts of liquid or gas samples. The sensing properties are
      investigated using finite elements method. The results demonstrate that the
      plasmonic sensor has a relatively high sensitivity of 1,010 nm/RIU, and the
      corresponding sensing resolution is 9.9 * 10(-5) RIU. The sensor has a relatively
      high quality factor of 35, which is beneficial for identifying each transmission
      spectrum. More importantly, the sensitivity is not sensitive to changes of
      structure parameters, which means that the sensitivity of the sensor is immune to
      the fabrication deviation. In addition, with a transmittance of 5% at the
      resonant wavelength, this plasmonic structure can also be employed as a filter.
      In addition, by filling material like LiNbO3 or liquid crystal in the circular
      resonator, this filter can realize an adjustable wavelength-selective
      characteristic in a wide band. 

PMID- 25991914
TI  - Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on
      human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis.
AB  - Photodynamic therapy (PDT) involves the action of photons on photosensitive
      molecules, where atomic oxygen or OH(-) molecular species are locally released on
      pathogenic human cells, which are mainly carcinogenic, thus causing cell
      necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions
      near the cell/nanodrug system that control both the level of intracellular
      translocation of nanoparticles in the pathogenic cell and their agglomeration on
      the cell membrane. Dendrimers are considered one of the most effective and
      promising drug carriers because of their relatively low toxicity and negligible
      activation of complementary reactions. Polyamidoamine (PAMAM) dendrite delivery
      of PDT agents has been investigated in the last few years for tumour selectivity,
      retention, pharmacokinetics and water solubility. Nevertheless, their use as drug
      carriers of photosensitizing molecules in PDT for cardiovascular disease,
      targeting the selective necrosis of macrophage cells responsible for atheromatous
      plaque growth, has never been investigated. Furthermore, the level of
      aggregation, translocation and nanodrug delivery efficacy of PAMAM dendrimers or
      PAMAM/zinc phthalocyanine (ZnPc) conjugates on human atheromatous tissue and
      endothelial cells is still unknown. In this work, the aggregation of PAMAM zero
      generation dendrimers (G0) acting as drug delivery carriers, as well as
      conjugated G0 PAMAM dendrimers with a ZnPc photosensitizer, to symptomatic and
      asymptomatic human carotid tissues was investigated by using atomic force
      microscopy (AFM). For the evaluation of the texture characteristics of the AFM
      images, statistical surface morphological and fractal analytical methodologies
      and Minkowski functionals were used. All statistical quantities showed that the
      deposition of nanodrug carriers on healthy tissue has an inverse impact when
      comparing to the deposition on atheromatous tissue with different aggregation
      features between G0 and G0/ZnPc nanoparticles and with considerably larger
      G0/ZnPc aggregations on the atheromatous plaque. The results highlight the
      importance of using PAMAM dendrimer carriers as a novel and promising PDT
      platform for atherosclerosis therapies. 

PMID- 25991916
TI  - Green synthesis of gold nanoparticles using aspartame and their catalytic
      activity for p-nitrophenol reduction.
AB  - We demonstrated a facile and environmental-friendly approach to form gold
      nanoparticles through the reduction of HAuCl4 by aspartame. The single
      crystalline structure was illustrated by transmission electron microscopy (TEM)
      and X-ray diffraction (XRD). The energy-dispersive X-ray spectroscopy (EDS) and
      Fourier transform infrared (FTIR) results indicated that aspartame played a
      pivotal role in the reduction and stabilization of the gold crystals. The
      crystals were stabilized through the successive hydrogen-bonding network
      constructed between the water and aspartame molecules. Additionally, gold
      nanoparticles synthesized through aspartame were shown to have good catalytic
      activity for the reduction of p-nitrophenol to p-aminophenol in the presence of
      NaBH4. 

PMID- 25991917
TI  - Changes in glycoprotein expression between primary breast tumour and synchronous
      lymph node metastases or asynchronous distant metastases.
AB  - BACKGROUND: Breast cancer is a very heterogeneous disease and some patients are
      cured by the surgical removal of the primary tumour whilst other patients suffer
      from metastasis and spreading of the disease, despite adjuvant therapy. A number
      of prognostic and treatment predictive factors have been identified such as
      tumour size, oestrogen (ER) and progesterone (PgR) receptor status, human
      epidermal growth factor receptor type 2 (HER2) status, histological grade, Ki67
      and age. Lymph node involvement is also assessed during surgery to determine if
      the tumour has spread which requires dissection of the axilla and adjuvant
      treatment. The prognostic and treatment predictive factors assessing the nature
      of the tumour are all routinely based on the status of the primary tumour.
      RESULTS: We have analysed a unique tumour set of fourteen primary breast cancer
      tumours with matched synchronous axillary lymph node metastases and a set of nine
      primary tumours with, later developed, matched distant metastases from different
      sites in the body. We used a pairwise tumour analysis (from the same individual)
      since the difference between the same tumour-type in different patients was
      greater. Glycopeptide capture was used in this study to selectively isolate and
      quantify N-linked glycopeptides from tumours mixtures and the captured
      glycopeptides were subjected to label-free quantitative tandem mass spectrometry
      analysis. Differentially expressed proteins between primary tumours and matched
      lymph node metastasis and distant metastasis were identified. Two of the top
      hits, ATPIF1 and tubulin beta-chain were validated by immunohistochemistry to be
      differentially regulated. CONCLUSIONS: We show that the expression of a large
      number of glycosylated proteins change between primary tumours and matched lymph
      node metastases and distant metastases, confirming that cancer cells undergo a
      molecular transformation during the spread to a secondary site. The proteins are
      part of important pathways such as cell adhesion, migration pathways and immune
      response giving insight into molecular changes needed for the tumour to spread.
      The large difference between primary tumours and lymph node and distant
      metastases also suggest that treatment should be based on the phenotype of the
      lymph node and distant metastases.

PMID- 25991918
TI  - The interplay between immune maturation, age, chronic viral infection and
      environment.
AB  - BACKGROUND: The worldwide increase in life expectancy has been associated with an
      increase in age-related morbidities. The underlying mechanisms resulting in
      immunosenescence are only incompletely understood. Chronic viral infections, in
      particular infection with human cytomegalovirus (HCMV), have been suggested as a
      main driver in immunosenescence. Here, we propose that rhesus macaques could
      serve as a relevant model to define the impact of chronic viral infections on
      host immunity in the aging host. We evaluated whether chronic rhesus CMV (RhCMV)
      infection, similar to HCMV infection in humans, would modulate normal
      immunological changes in the aging individual by taking advantage of the unique
      resource of rhesus macaques that were bred and raised to be Specific Pathogen
      Free (SPF-2) for distinct viruses. RESULTS: Our results demonstrate that normal
      age-related immunological changes in frequencies, activation, maturation, and
      function of peripheral blood cell lymphocytes in humans occur in a similar manner
      over the lifespan of rhesus macaques. The comparative analysis of age-matched SPF
      2 and non-SPF macaques that were housed under identical conditions revealed
      distinct differences in certain immune parameters suggesting that chronic
      pathogen exposure modulated host immune responses. All non-SPF macaques were
      infected with RhCMV, suggesting that chronic RhCMV infection was a major
      contributor to altered immune function in non-SPF macaques, although a causative
      relationship was not established and outside the scope of these studies. Further,
      we showed that immunological differences between SPF-2 and non-SPF macaques were
      already apparent in adolescent macaques, potentially predisposing RhCMV-infected
      animals to age-related pathologies. CONCLUSIONS: Our data validate rhesus
      macaques as a relevant animal model to study how chronic viral infections
      modulate host immunity and impact immunosenescence. Comparative studies in SPF-2
      and non-SPF macaques could identify important mechanisms associated with
      inflammaging and thereby lead to new therapies promoting healthy aging in humans.

PMID- 25991919
TI  - Beneficial effects of inorganic nitrate/nitrite in type 2 diabetes and its
      complications.
AB  - BACKGROUND AND AIM: The ability of inorganic nitrate and nitrite to convert to
      nitric oxide (NO), and some of its properties e.g. regulation of glucose
      metabolism, vascular homeostasis, and insulin signaling pathway, have recently
      raised the hypothesis that inorganic nitrate and nitrite could be potential
      therapeutic agents in type 2 diabetes. In this review, we reviewed experimental
      and clinical studies investigating the effect of nitrate/nitrite administration
      on various aspects of type 2 diabetes. FINDINGS: Studies showed that an altered
      metabolism of nitrate/nitrite and impaired NO pathway occurs in diabetes which
      could contribute to its complications. Some important beneficial properties,
      including regulation of glucose homeostasis and insulin signaling pathway,
      improvement of insulin resistance and vascular function, hypotensive,
      hypolipidemic as well as anti-inflammatory and anti-oxidative effects have been
      observed following administration of inorganic nitrate/nitrite. CONCLUSION: It
      seems that dietary nitrate/nitrite could be a compensatory fuel for a disrupted
      nitrate/nitrite/NO pathway and related disorders in diabetes. Although some
      beneficial properties of nitrate/nitrite have been reported by experimental
      investigations, long-term clinical studies with various doses of inorganic
      nitrate/nitrite supplementation, are recommended to confirm these effects.

PMID- 25991920
TI  - Epidemiology of spinal injuries in the United Arab Emirates.
AB  - AIM: To assess the risk factors, mechanism of injury, and clinical outcome of
      hospitalized patients with spinal injuries in order to recommend preventive
      measures. METHODS: Patients with spinal injuries admitted to Al Ain Hospital,
      United Arab Emirates (UAE) for more than 24 h or who died after arrival to the
      hospital were studied over 3 years. Demography, location and time of injury,
      affected body regions, hospital and ICU stay, and outcome were analyzed. RESULTS:
      239 patients were studied, 90 % were males, and 84 % were in the productive years
      of 25-54. Majority were from the Indian subcontinent (56 %). Road was the most
      common location for spinal injury (47 %), followed by work (39 %). The most
      common mechanism of injury was traffic collisions (48 %) followed by fall from
      height (39 %) and fall from the same level (9 %). UAE nationals were often
      injured at road and home compared with non-UAE nationals, who were more injured
      at work (p < 0.0001). Patients falling from the same level were older (p = 0.001)
      and predominantly females (p < 0.0001) when compared with other mechanisms.
      Spinal fractures were more common in the lumbar region (57 %). Eleven patients (5
      %) sustained paraplegia and five (4 %) patients died. INTERPRETATION: Traffic
      injuries and falls were the leading causes for spinal injuries in the UAE.
      Expatriate males are at high risk for fall from height, UAE national males for
      traffic injuries and females for falls at the same level at homes. Prevention
      should focus on traffic and home injuries for UAE nationals and occupational
      safety for expatriate workers.

PMID- 25991921
TI  - Genetic variability in E6 and E7 oncogenes of human papillomavirus Type 16 from
      Congolese cervical cancer isolates.
AB  - BACKGROUND: The molecular epidemiological studies showed that some variants of
      HPV-16, distributed geographically, would present a higher risk of causing
      cervical cancer. This study aimed to analyze nucleotide changes of HPV-16 E6 and
      E7 genomic regions from infected Southwestern Congolese women. METHODS: DNA of
      twenty HPV-16 isolates was analyzed by amplifying the E6 and E7 genes using type
      specific primers PCR and direct sequencing. The sequences obtained were aligned
      with the HPV-16 GenBank reference sequences. RESULTS: Thirteen (65.0%) out of 20
      DNA-samples were successfully amplified. Genetic analysis revealed 18 and 4
      nucleotide changes in E6 and E7 genomic regions respectively. The most frequently
      observed nucleotide variations were the missense C143G, G145T and C335T in E6
      (100%), leading to the non-synonymous amino acid variation Q14D and H78Y. E7
      genomic region was found to be highly conserved with two most common T789C and
      T795G (100%) silent variations. All HPV-16 variants identified belonged to the
      African lineage: 7 (53.8%) belonged to Af-1 lineage and 6 (46.1%) to Af-2
      lineage. The missense mutation G622A (D21N) in the E7 region seems to be
      described for the first time in this study. CONCLUSION: This study reported for
      the first time the distribution of HPV-16 E6 and E7 genetic variants in infected
      women from southwest Congo. The findings confirmed almost ascendancy of the
      African lineage in our study population.

PMID- 25991922
TI  - Access to healthcare for the most vulnerable migrants: a humanitarian crisis.
AB  - A series of Medecins Sans Frontieres projects for irregular migrants over the
      past decade have consistently documented high rates of 14 physical and sexual
      trauma, extortion and mental illness amidst severe healthcare, food, and housing
      limitations. Complex interventions were needed to begin to address illness and
      barriers to healthcare and to help restore dignity to the most vulnerable women,
      children and men. Promising interventions included mobile clinics, use of
      cultural mediators, coordination with migrant-friendly entities and NGOs and
      integrating advocacy programs and mental health care with medical services.
      Ongoing interventions, research and coordination are needed to address this
      neglected humanitarian crisis. 

PMID- 25991923
TI  - New generation biofuel: continuous acidogenesis of sucrose-raffinose mixture
      simulating vinasse is promoted by gamma-alumina pellets.
AB  - BACKGROUND: This investigation comprises a contribution on the production of a
      new generation biofuel using the industrial liquid waste of bioethanol
      distilleries, known as vinasse. This study focuses on the exploitation of vinasse
      as an acidogenesis substrate for volatile fatty acids and simultaneous ethanol
      production. These products can be used for ester production, which is the new
      generation biofuel. Therefore, the aims of the present study are (i) to examine
      any promotional effect of gamma-alumina on acidogenesis of a sucrose-raffinose
      mixture simulating vinasse, (ii) to study the operational stability of the
      continuous acidogenesis of sucrose and raffinose and subsequently of vinasse, and
      (iii) to determine the volatile fatty acid chemical composition and ethanol
      formation. RESULTS: Batch acidogenesis of sucrose and raffinose mixtures showed
      that gamma-alumina promoted fermentation leading to an increase in the volatile
      fatty acid yield factor from 40% to 95% compared to free cells. The application
      of the system in continuous mode for more than 3 months showed that the
      continuous volatile fatty acid productivity obtained was higher than 7 g/L/day.
      Lactic acid was the predominant acid when sucrose and raffinose were used while
      butyric acid in the case of vinasse. The highest volatile fatty acid
      concentration reached was 19 g/L for vinasse. CONCLUSIONS: A promoting effect of
      gamma-alumina in acidogenic fermentation of sucrose-raffinose and vinasse is
      reported. Continuous acidogenesis of sucrose-raffinose mixtures and vinasse using
      gamma-alumina with immobilized cells showed high operational stability (more than
      3 months). These findings result in easy scale up of the process that will
      produce a high annual added value of $11,000,000 in a daily bioethanol production
      plant of 50,000 L.

PMID- 25991925
TI  - Genome sequences of the Shiga-like toxin-producing Escherichia coli NCCP15655 and
      NCCP15656.
AB  - BACKGROUND: Virulence genes can spread among commensal bacteria through
      horizontal gene transfer. The bacterium with novel virulence factors may pose a
      severe threat to public health because of the absence of a management system
      unlike known pathogens. Especially, when a pathogenic bacterium acquires a new
      kind of virulence genes, it tends to exhibit stronger virulence. In this study,
      we analyzed the genomes of the two strains of Escherichia coli that were isolated
      from the feces of patients with diarrhea and produce Shiga-like toxin. RESULTS:
      Phylogenetic analysis of conserved genes and average nucleotide identity values
      of the draft genome sequences indicate that strains NCCP15655 and NCCP15656,
      isolated from diarrhea patients, belong to the B1 group of E. coli and form a
      sister clade with strain E24377A. However, the proportion the genes belonging to
      the subsystem category "phages, prophages, transposable elements, plasmids" and
      "virulence, disease and defense" are higher than E24377A. Indeed, in their
      genomes, genes encoding Shiga toxin type 1, Shiga toxin type 2, and type 1
      fimbriae were detected. Moreover, a plasmid encoding hemolysin and
      entropathogenic E. coli secreted protein C was identified in both genomes.
      CONCLUSIONS: Through the genome analysis of NCCP15655 and NCCP15656, we
      identified two types of Shiga-like toxin genes that could be responsible for the
      manifestation of the diarrhea symptom. However, the LEE island, which is one of
      the major virulence factors of enterohemorrhagic E. coli, was not detected and
      they are most similar with non-Shiga-like toxin-producing E. coli at the genomic
      level. NCCP15655 and NCCP15656 will be good examples of Shiga-like toxin
      producing E. coli whose genomes are not as similar with typical enterohemorrhagic
      E. coli as non-Shiga-like toxin-producing E. coli.

PMID- 25991924
TI  - Transcriptomic landscape of lncRNAs in inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a complex multi-factorial
      inflammatory disease with Crohn's disease (CD) and ulcerative colitis (UC) being
      the two most common forms. A number of transcriptional profiling studies have
      provided compelling evidence that describe the role of protein-coding genes and
      microRNAs in modulating the immune responses in IBD. METHODS: In the present
      study, we performed a genome-wide transcriptome profiling of lncRNAs and protein
      coding genes in 96 colon pinch biopsies (inflamed and non-inflamed) extracted
      from multiple colonic locations from 45 patients (CD = 13, UC = 20, controls =
      12) using an expression microarray platform. RESULTS: In our study, we identified
      widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and
      non-inflamed CD and UC compared to the healthy controls. In cases of inflamed CD
      and UC, we identified 438 and 745 differentially expressed lncRNAs, respectively,
      while in cases of the non-inflamed CD and UC, we identified 12 and 19
      differentially expressed lncRNAs, respectively. We also observed significant
      enrichment (P-value <0.001, Pearson's Chi-squared test) for 96 differentially
      expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility
      loci. Furthermore, we found strong positive expression correlations for the
      intersecting and cis-neighboring differentially expressed IBD loci-associated
      lncRNA-protein-coding gene pairs. The functional annotation analysis of
      differentially expressed genes revealed their involvement in the immune response,
      pro-inflammatory cytokine activity and MHC protein complex. CONCLUSIONS: The
      lncRNA expression profiling in both inflamed and non-inflamed CD and UC
      successfully stratified IBD patients from the healthy controls. Taken together,
      the identified lncRNA transcriptional signature along with clinically relevant
      parameters suggest their potential as biomarkers in IBD.

PMID- 25991926
TI  - Shift work and its association with metabolic disorders.
AB  - Although the health burden of shift work has not been extensively studied,
      evidence suggests that it may affect the metabolic balance and cause obesity and
      other metabolic disorders. Sleep deprivation, circadian desynchronization and
      behavioral changes in diet and physical activity are among the most commonly
      mentioned factors in studies of the association between night work and metabolic
      disorders. Individual adaptation to night work depends greatly on personal
      factors such as family and social life, but occupational interventions may also
      make a positive contribution to the transition to shift work, such as exposure to
      bright lights during the night shift, melatonin use, shift regularity and
      clockwise rotation, and dietary adaptations for the metabolic needs of night
      workers. The evaluation of the impact of night work on health and of the
      mechanisms underlying this relationship can serve as a basis for intervention
      strategies to minimize the health burden of shift work. This review aimed to
      identify highlights regarding therapeutic implications following the association
      between night and shift work and metabolic disorders, as well as the mechanisms
      and pathways responsible for these relationships. 

PMID- 25991927
TI  - Cumulative, additive benefits of memantine-donepezil combination over component
      monotherapies in moderate to severe Alzheimer's dementia: a pooled area under the
      curve analysis.
AB  - INTRODUCTION: Treatment in moderate or severe Alzheimer's disease (AD) often
      involves adding memantine to a cholinesterase-inhibitor (ChEI: donepezil,
      galantamine, rivastigmine). Evidence from six-month randomized trials and long
      term observational studies supports superiority of memantine-ChEI combination to
      ChEI monotherapy. We utilized area-under-the-curve (AUC) analysis to assess six
      month cumulative treatment efficacy of memantine-donepezil combination versus
      component monotherapies on individual clinical domains and on a composite index.
      METHODS: Data were pooled from 1,408 individuals with moderate to severe AD from
      four six-month randomized trials of memantine monotherapy (n = 570) or add-on
      therapy (donepezil-only subset: n = 847). AUC changes from baseline on measures
      of cognition (SIB), function (ADCS-ADL19), behavior (NPI), global status (CIBIC
      Plus), and a composite index (4D-CI: equally weighted composite of four domain
      measures) were calculated using the trapezoidal rule and evaluated via analysis
      of covariance (ANCOVA) (2-sided-alpha = 0.05). AUC results were contrasted with
      visit-by-visit changes from baseline ("snapshot analysis"), performed using a
      mixed-effects model with repeated measures (MMRM). RESULTS: Over the entire six
      month period, placebo-only treatment was associated with significant cumulative
      worsening on all outcomes. Memantine-donepezil combination showed significantly
      greater AUC improvements (point x week) on the SIB, NPI, and CIBIC-Plus than
      placebo-donepezil (SIB: 68.4 versus 32.0, P = 0.019; NPI: -74.3 versus -28.2, P =
      0.003; CIBIC-Plus: -2.5 versus 1.4, P = 0.006) and memantine-only monotherapies
      (SIB: 68.4 versus 12.0, P <0.001; NPI: -74.3 versus -7.4, P <0.001; CIBIC-Plus: 
      2.5 versus 2.7, P <0.001), whereas these comparisons were not significant for the
      ADCS-ADL19 (memantine-donepezil (1.4) versus placebo-donepezil (-0.9), P = 0.407;
      versus memantine-only (-12.2), P = 0.310). Composite index analysis demonstrated
      significant cumulative advantages of memantine-donepezil combination (630.0) over
      placebo-donepezil (344.7, P <0.001) and memantine-only (152.1, P <0.001)
      treatments. Combining memantine and donepezil had an additive effect. Compared
      with AUC analysis, baseline-to-endpoint change-score analysis underestimated
      effects of combination therapy, monotherapies, or both. CONCLUSIONS: This large
      pooled area-under-the-curve analysis of randomized-trial data in moderate to
      severe AD provides ecologically valid support that adding memantine to stable
      donepezil results in overall clinical benefits that are additive compared with
      individual monotherapies, continue to accumulate through six-month treatment, and
      are at least 50% greater than those of monotherapies.

PMID- 25991929
TI  - Editorial.

PMID- 25991928
TI  - Differential SINE evolution in vesper and non-vesper bats.
AB  - BACKGROUND: Short interspersed elements (SINEs) have a powerful influence on
      genome evolution and can be useful markers for phylogenetic inference and
      population genetic analyses. In this study, we examined survey sequence and whole
      genome data to determine the evolutionary dynamics of Ves SINEs in the genomes of
      11 bats, nine from Vespertilionidae. RESULTS: We identified 41 subfamilies of Ves
      and linked several to specific lineages. We also revealed substantial differences
      among lineages including the observation that Ves accumulation and Ves subfamily
      diversity is significantly higher in vesper as opposed to non-vesper bats. This
      is especially interesting when one considers the increased transposable element
      diversity of vesper bats in general. CONCLUSIONS: Our data suggest that survey
      sequencing and genome mining are valuable tools to investigate SINE evolution
      among related lineages and can provide substantial information about the ability
      of SINEs to proliferate in diverse genomes. This method would also be a useful
      first step in determining which subfamilies would be the best to target when
      developing SINEs as markers for phylogenetic and population genetic analyses.

PMID- 25991930
TI  - Effects of hearing aids in the balance, quality of life and fear to fall in
      elderly people with sensorineural hearing loss.
AB  - INTRODUCTION:  The aging process provokes structural modifications and functional
      to it greets, compromising the postural control and central processing. Studies
      have boarded the necessity to identify to the harmful factors of risk to aged the
      auditory health and security in stricken aged by auditory deficits and with
      alterations of balance. OBJECTIVE:  To evaluate the effect of auditory prosthesis
      in the quality of life, the balance and the fear of fall in aged with bilateral
      auditory loss. METHOD:  Carried through clinical and experimental study with 56
      aged ones with sensorineural auditory loss, submitted to the use of auditory
      prosthesis of individual sonorous amplification (AASI). The aged ones had
      answered to the questionnaires of quality of life Short Form Health Survey (SF
      36), Falls Efficacy International Scale- (FES-I) and the test of Berg Balance
      Scale (BBS). After 4 months, the aged ones that they adapted to the use of the
      AASI had been reevaluated. RESULTS:  It had 50% of adaptation of the aged ones to
      the AASI. It was observed that the masculine sex had greater difficulty in
      adapting to the auditory device and that the variable age, degree of loss,
      presence of humming and vertigo had not intervened with the adaptation to
      auditory prosthesis. It had improvement of the quality of life in the dominance
      of the State General Health (EGS) and Functional Capacity (CF) and of the
      humming, as well as the increase of the auto-confidence after adaptation of
      auditory prosthesis. CONCLUSION:  The use of auditory prosthesis provided the
      improvement of the domains of the quality of life, what it reflected consequently
      in one better auto-confidence and in the long run in the reduction of the fear of
      fall in aged with sensorineural auditory loss.

PMID- 25991931
TI  - Hearing symptoms personal stereos.
AB  - INTRODUCTION:  Practical and portable the personal stereos if had become almost
      indispensable accessories in the day the day. Studies disclose that the portable
      players of music can cause auditory damages in the long run for who hear music in
      high volume for a drawn out time. OBJECTIVE:  to verify the prevalence of
      auditory symptoms in users of amplified players and to know its habits of use
      METHOD:  Observational prospective study of transversal cut carried through in
      three institutions of education of the city of Salvador BA, being two of public
      net and one of the private net. 400 students had answered to the questionnaire,
      of both the sex, between 14 and 30 years that had related the habit to use
      personal stereos. RESULTS:  The symptoms most prevalent had been hyperacusis
      (43.5%), auricular fullness (30.5%) and humming (27.5), being that the humming is
      the symptom most present in the population youngest. How much to the daily
      habits: 62.3% frequent use, 57% in raised intensities, 34% in drawn out periods.
      An inverse relation between exposition time was verified and the band of age (p =
      0,000) and direct with the prevalence of the humming. CONCLUSION:  Although to
      admit to have knowledge on the damages that the exposition the sound of high
      intensity can cause the hearing, the daily habits of the young evidence the
      inadequate use of the portable stereos characterized by long periods of
      exposition, raised intensities, frequent use and preference for the insertion
      phones. The high prevalence of symptoms after the use suggests a bigger risk for
      the hearing of these young.

PMID- 25991932
TI  - Evaluation of the benefit of amplification in children fitted with hearing aids.
AB  - INTRODUCTION:  In Brazil, it is rare studies with using deaf children of auditory
      device above of seven years. OBJECTIVE:  To investigate the benefit supplied for
      the amplification in deaf children to 7 years old to 11 years old using auditory
      device, under the perspective of the proper child and the adults with who it more
      coexists, and to verify if the time of conviviality of the adults with the child
      intervenes with their answers. METHOD:  One is about a clinical and experimental
      study. They had participated of the study 48 citizens, divided in 4 distinct
      groups: G1- 12 deaf children; G2- 12 adults with average companionship of 40
      weekly hours with the deaf child; G3- 12 adults with average companionship of 20
      weekly hours with the deaf child; G4- 12 adults with average companionship of 10
      weekly hours with the deaf child. All the children were using of device
      bilaterally and presented auditory loss of severe or deep degree. RESULTS:  The
      results indicate damage in the auditory abilities of the children evaluated had
      to the difficulties faced for them to listen to elements gifts in situations of
      its daily one. The time of companionship with the child did not have differences
      in the results between the different groups in agreement. CONCLUSION:  The
      viability of the evaluation of the proportionate benefit for the auditory device
      in children was evidenced clinically on the basis of the information of the
      family. The device of individual sonorous amplification exerted influence in the
      auditory abilities of the evaluated children, although the proportionate benefit
      for its use to be lesser of what the waited one.

PMID- 25991933
TI  - Prevalence of auditory changes in newborns in a teaching hospital.
AB  - INTRODUCTION:  The precocious diagnosis and the intervention in the deafness are
      of basic importance in the infantile development. The loss auditory and more
      prevalent than other joined riots to the birth. OBJECTIVE:  Esteem the prevalence
      of auditory alterations in just-born in a hospital school. METHOD:  Prospective
      transversal study that evaluated 226 just-been born, been born in a public
      hospital, between May of 2008 the May of 2009. RESULTS:  Of the 226 screened, 46
      (20.4%) had presented absence of emissions, having been directed for the second
      emission. Of the 26 (56.5%) children who had appeared in the retest, 8 (30.8%)
      had remained with absence and had been directed to the Otolaryngologist. Five
      (55.5%) had appeared and had been examined by the doctor. Of these, 3 (75.0%) had
      presented normal otoscopy, being directed for evaluation of the Evoked Potential
      Auditory of Brainstem (PEATE). Of the total of studied children, 198 (87.6%) had
      had presence of emissions in one of the tests and, 2 (0.9%) with deafness
      diagnosis. CONCLUSION:  The prevalence of auditory alterations in the studied
      population was of 0,9%. The study it offers given excellent epidemiologists and
      it presents the first report on the subject, supplying resulted preliminary
      future implantation and development of a program of neonatal auditory selection.

PMID- 25991934
TI  - Multifrequency tympanometry in infants.
AB  - INTRODUCTION:  The use of conventional tympanometry is not sufficiently sensitive
      to detect all cases of middle ear changes, and this hinders accurate diagnosis.
      OBJECTIVE:  To characterize acoustic immittance measures of infants from 0 to 3
      months of age using multifrequency tympanometry in a prospective study. METHOD: 
      54 infants from 0 to 3 months of age were evaluated. The inclusion criteria
      included absence of respiratory infections during the evaluation, presence of
      transient evoked otoacoustic emissions, and absence of risk indicators for
      hearing loss. The subjects were evaluated by an audiologic interview, a visual
      inspection of the ear canal, and measures of acoustic immittance at the
      frequencies of 226 Hz, 678 Hz, and 1,000 Hz. Tympanometric records of the
      occlusion effect, tympanometric curve type, tympanometric peak pressure,
      equivalent ear canal volume, and peak compensated static acoustic admittance were
      collected. RESULTS:  The results indicated the presence of an occlusion effect
      (2.88% at 226 Hz, 4.81% at 678 Hz and 3.85% at 1,000 Hz), predominance of a
      tympanometric curve with a single peak (65.35% at 226 Hz, 81.82% at 678 Hz, and
      77.00% at 1,000 Hz), and tympanometric peak pressure ranging from -155 to 180
      daPa. Further, the equivalent ear canal volume increased with the frequency of
      the probe (0.64 mL at 226 Hz, 1.63 mho at 678 Hz, and 2.59 mmho at 1,000 Hz) and
      the peak compensated static acoustic admittance values increased with an increase
      in frequency (0.51 mL at 226 Hz, 0.55 mmho at 678 Hz and 1.20 mmho at 1,000 Hz).
      93.06% of the tympanograms were classified as normal at 226 Hz, 81.82% at 678 Hz,
      and 77.00 % at 1,000 Hz, respectively. CONCLUSION:  Taken together, these results
      demonstrated that utilizing these evaluations made it possible to characterize
      the acoustic immittance measures of infants.

PMID- 25991935
TI  - Treatment of retroauricular keloids: Revision of cases treated at the ENT service
      of HC/UFPR.
AB  - INTRODUCTION:  Keloids are benign tumors arising from abnormal healing of the
      skin, and there are several procedures available for their treatment. OBJECTIVE: 
      The objective of this study was to evaluate the outcomes of patients undergoing
      treatment of keloids after ear, nose, and throat (ENT) surgeries at our service
      center. METHOD:  We conducted thorough, retrospective and prospective analysis of
      records of patients undergoing treatment of retroauricular keloids at our center.
      RESULTS:  Nine patients were evaluated, and 6 underwent resection and adjuvant
      beta-therapy, 2 underwent resection with local application of corticosteroids,
      and only 1 underwent resection without adjuvant therapy. There was no recurrence
      of keloids in patients that were treated with beta-therapy in the early
      postoperative period. One patient had relapsed despite corticosteroid
      administration and late beta-therapy. DISCUSSION:  Several techniques have been
      used for the treatment of retroauricular keloids, and beta-therapy is thought to
      yield the best results, followed by the use of intralesional corticosteroids.
      CONCLUSION:  Treatment of retroauricular keloids remains a challenge. While new
      techniques are being developed, resection followed by early beta-therapy is still
      the best treatment option.

PMID- 25991937
TI  - Correlation between nasopharyngoscopy and cephalometry in the diagnosis of
      hyperplasia of the pharyngeal tonsils.
AB  - INTRODUCTION:  Hyperplasia of the pharyngeal tonsil is one of the main causes of
      mouth breathing, and accurate diagnosis of this alteration is important for
      proper therapeutic planning. Therefore, studies have been conducted in order to
      provide information regarding the procedures that can be used for the diagnosis
      of pharyngeal obstruction. OBJECTIVE:  To verify the correlation between
      nasopharyngoscopy and cephalometric examinations in the diagnosis of pharyngeal
      tonsil hyperplasia. METHOD:  This was a cross-sectional, clinical, experimental,
      and quantitative study. Fifty-five children took part in this study, 30 girls and
      25 boys, aged between 7 and 11 years. The children underwent
      nasofibropharyngoscopic and cephalometric evaluation to determine the grade of
      nasopharyngeal obstruction. The Spearman's rank correlation coefficient at the 5%
      significance level was used to verify the correlation between these exams.
      RESULTS:  In the nasopharyngoscopy evaluation, most children showed grade 2 and 3
      hyperplasia of the pharyngeal tonsil, which was followed by grade 1. In the
      cephalometry assessment, most children showed grade 1 hyperplasia of the
      pharyngeal tonsil, which was followed by grade 2. A statistically significant
      regular positive correlation was observed between the exams. CONCLUSION:  It was
      concluded that the evaluation of the pharyngeal tonsil hyperplasia could be
      carried out by fiber optic nasopharyngoscopy and cephalometry, as these
      examinations were regularly correlated. However, it was found that cephalometry
      tended to underestimate the size of the pharyngeal tonsil relative to
      nasopharyngoscopy.

PMID- 25991936
TI  - Expectation as a factor of influence on the success of use of hearing aids in
      elderly individuals.
AB  - INTRODUCTION:  Auditory prosthesis is distinguished in function of the lesser
      technologies that become them each time, more powerful and efficient. The
      marketing can generate unreal expectations how much to the results with the
      amplification use, mainly in inexperienced individuals. OBJECTIVE:  To verify the
      relation between expectations and success of the process of election and
      adaptation of auditory prosthesis in aged. METHOD:  Clinical and experimental
      study, 16 aged, inexperienced individuals with the amplification use, the
      election and adaptation of auditory prosthesis had been evaluated 15 days before
      and after. Questionnaire for evaluation of the expectations of aged the adult
      individual was used "/, new user of auditory prosthesis", Hearing Handicap
      Inventory will be the Elderly/Screening Version, for evaluation of the perception
      of the restriction of participation and the International Questionnaire - Device
      of Amplification Sonora Individual (QI-AASI), to verify the subjective benefit
      with the use of the auditory prosthesis. The Percentile Index of Recognition of
      Sentences in Silence was determined (IPRSS), by means of the test Lists of
      Sentences in Portuguese to verify the objective benefit of the adaptation. The
      data had been analyzed by means of not-parametric test, with level of
      significance of 5%. RESULTS:  The entire sample presented positive expectations.
      Subjectively benefit for the reduction of the perception of the participation
      restriction and for the positive evaluation of the adaptation, evidenced for the
      QI-AASI was verified. OBJECTIVE the improvement of the IPRSS with the use of
      auditory prosthesis also evidenced benefits. CONCLUSION:  The expectation how
      much to the results with the amplification use, it was factor of negative
      influence in the success of the process of election and adaptation of auditory
      prosthesis, in the subjective scope.

PMID- 25991939
TI  - Prevalence of tinnitus in elderly individuals with and without history of
      occupational noise exposure.
AB  - INTRODUCTION:  The various metabolic and circulatory alterations that are related
      to noise exposure may cause the onset of several symptoms, including tinnitus.
      OBJECTIVE:  The purpose of the study was to assess the prevalence of tinnitus
      complaints in elderly individuals with and without history of occupational noise
      exposure. METHOD:  This prospective study was conducted in a sample population
      consisting of 502 individuals aged over 60 years, by anamnesis and audiological
      evaluation. The variables that were studied were the frequency of tinnitus and
      the history of occupational noise. Logistic regression was used to control for
      potential confusion or modifications caused by the effects of the other variables
      on the associations of interest. RESULTS AND DISCUSSION:  Tinnitus was reported
      in 50% of the cases, with tinnitus reported in 40% of the elderly individuals
      with history of occupational noise exposure, and in 43% of controls (elderly
      individuals without history of occupational noise exposure). A high frequency of
      tinnitus was detected in the population under investigation, but there were no
      statistically significant associations between the presence of tinnitus and
      history of occupational noise exposure. CONCLUSION:  The results of this study
      may have occurred due to other factors such as the age of the individuals without
      history of occupational noise exposure.

PMID- 25991938
TI  - Single-stage laryngotracheal reconstruction for the treatment of subglottic
      stenosis in children.
AB  - INTRODUCTION:  In recent decades, airway reconstruction has become the treatment
      of choice for subglottic stenosis (SGS) in children, which is performed in either
      single or multiple stages. However, there is evidence in the literature that
      single-stage surgery is more effective. OBJECTIVE:  To evaluate the success rate
      of single-stage laryngotracheoplasty (LTP) and cricotracheal resection (CTR) in
      patients that were treated in our hospital. MATERIALS AND METHOD:  We performed a
      retrospective study of children undergoing laryngotracheal reconstruction.
      RESULTS:  Twenty-four children were included. The etiology of SGS was
      postintubation in 91.6% and congenital in 8.3%. One patient (4.2%) had grade 4
      SGS, 17 (70.8%) presented with grade 3 SGS, 4 (16.6%) had grade 2 SGS, 1 (4.2%)
      had grade 3 SGS associated with glottic stenosis, and 1 (4.2%) had grade 3 SGS
      with tracheal stenosis. We performed 26 LTPs and 3 CTRs. Decannulation rates were
      66% in the CTR procedures and 85.7% in the LTP procedures; the overall
      decannulation rate was 83.3%. All children presented with fever in the
      postoperative period, but were afebrile after the tube was removed. CONCLUSION: 
      Our series showed a decannulation rate of 83.3%.

PMID- 25991940
TI  - A study of the high-frequency hearing thresholds of dentistry professionals.
AB  - INTRODUCTION:  In the dentistry practice, dentists are exposed to harmful effects
      caused by several factors, such as the noise produced by their work instruments.
      In 1959, the American Dental Association recommended periodical hearing
      assessments and the use of ear protectors. Aquiring more information regarding
      dentists', dental nurses', and prosthodontists' hearing abilities is necessary to
      propose prevention measures and early treatment strategies. OBJECTIVE:  To
      investigate the auditory thresholds of dentists, dental nurses, and
      prosthodontists. METHOD:  In this clinical and experimental study, 44 dentists
      (Group I; GI), 36 dental nurses (Group II; GII), and 28 prosthodontists (Group
      III; GIII) were included, , with a total of 108 professionals. The procedures
      that were performed included a specific interview, ear canal inspection,
      conventional and high-frequency threshold audiometry, a speech reception
      threshold test, and an acoustic impedance test. RESULTS:  In the 3 groups that
      were tested, the comparison between the mean hearing thresholds provided evidence
      of worsened hearing ability relative to the increase in frequency. For the
      tritonal mean at 500 to 2,000 Hz and 3,000 to 6,000 Hz, GIII presented the worst
      thresholds. For the mean of the high frequencies (9,000 and 16,000 Hz), GII
      presented the worst thresholds. CONCLUSION:  The conventional hearing threshold
      evaluation did not demonstrate alterations in the 3 groups that were tested;
      however, the complementary tests such as high-frequency audiometry provided
      greater efficacy in the early detection of hearing problems, since this
      population's hearing loss impaired hearing ability at frequencies that are not
      tested by the conventional tests. Therefore, we emphasize the need of utilizing
      high-frequency threshold audiometry in the hearing assessment routine in
      combination with other audiological tests.

PMID- 25991941
TI  - Lateral intercrural suture in the caucasian nose: Decreased domal divergence
      angle in endonasal rhinoplasty without delivery.
AB  - INTRODUCTION:  Several techniques can be performed to improve nasal tip
      definition such as cartilage resection, tip grafts, or sutures. Objctive: To
      evaluate the outcome of lateral intercrural suture at the lower lateral cartilage
      by endonasal rhinoplasty with a basic technique without delivery in decreasing
      the angle of domal divergence and improving the nasal tip definition. METHOD: 
      This prospective study was performed in 64 patients in which a suture was made on
      the board head of the lower lateral cartilage in the joint between the dome and
      lateral crus, using polydioxanone (PDS) with sharp, curved needle. RESULTS:  In
      all of the cases, better definition of the nasal tip was achieved by intercrural
      suturing for at least 6 months postoperatively. CONCLUSION:  Lateral intercrural
      suture of the lower lateral cartilage provides improved nasal tip definition and
      can be performed by endonasal rhinoplasty without delivery in the Caucasian nose.

PMID- 25991942
TI  - Laryngeal complications by orotracheal intubation: Literature review.
AB  - INTRODUCTION:  The injuries caused for the orotracheal intubation are common in
      our way and widely told by literature. Generally the pipe rank of or consequence
      of its permanence in the aerial ways of the patient is caused by accidents in. It
      has diverse types of larynx injuries, caused for multiple mechanisms. OBJECTIVE: 
      To verify, in literature, the main causes of laryngeal complications after-
      orotracheal intubation and its mechanisms of injury. Revision of Literature: The
      searched databases had been LILACS, BIREME and SCIELO. Were updated, books and
      theses had been used, delimiting itself the period enters 1953 the 2009. The
      keywords used for the search of articles had been: complications, injuries,
      larynx, intubation, endotracheal, orotracheal, granulomas, stenosis. 59
      references had been selected. The used criteria of inclusion for the choice of
      articles had been the ones that had shown to the diverse types of injuries caused
      for the orotracheal intubation and its pathophysiology. FINAL CONSIDERATIONS: 
      This revision of literature was motivated by the comment in the practical clinic
      of a great number of laryngeal sequels in patients submitted to the orotracheal
      intubation. Of that is ahead important the knowledge, for the professionals of
      the area of health, the types of complications and its causes, with intention to
      prevent them, adopting measured of prevention of these injuries.

PMID- 25991943
TI  - Audition and exhibition to toluene - a contribution for the theme.
AB  - INTRODUCTION:  With the technological advances and the changes in the productive
      processes, the workers are displayed the different physical and chemical agents
      in its labor environment. The toluene is solvent an organic gift in glues, inks,
      oils, amongst others. OBJECTIVE:  To compare solvent the literary findings that
      evidence that diligent displayed simultaneously the noise and they have greater
      probability to develop an auditory loss of peripheral origin. METHOD:  Revision
      of literature regarding the occupational auditory loss in displayed workers the
      noise and toluene. RESULTS:  The isolated exposition to the toluene also can
      unchain an alteration of the auditory thresholds. These audiometric findings, for
      ototoxicity the exposition to the toluene, present similar audiograms to the one
      for exposition to the noise, what it becomes difficult to differentiate a
      audiometric result of agreed exposition - noise and toluene - and exposition only
      to the noise. CONCLUSION:  The majority of the studies was projected to generate
      hypotheses and would have to be considered as preliminary steps of an additional
      research. Until today the agents in the environment of work and its effect they
      have been studied in isolated way and the limits of tolerance of these, do not
      consider the agreed expositions. Considering that the workers are displayed the
      multiples agent and that the auditory loss is irreversible, the implemented tests
      must be more complete and all the workers must be part of the program of auditory
      prevention exactly displayed the low doses of the recommended limit of
      exposition.

PMID- 25991944
TI  - Cough: neurophysiology, methods of research, pharmacological therapy and
      phonoaudiology.
AB  - INTRODUCTION:  The cough is the more common respiratory symptom in children and
      adults. OBJECTIVE:  To present a revision on the neurophysiology and the methods
      for study of the consequence of the cough, as well as the pharmacotherapy and
      phonoaudiology therapy of the cough, based on the works published between 2005
      and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them
      to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of
      the cough involves activation of receiving multiples becomes vacant in the aerial
      ways and of neural projections of the nucleus of the solitary treatment for other
      structures of the central nervous system. Experimental techniques allow studying
      the consequence of the cough to the cellular and molecular level to develop new
      anti-cough agents. It does not have evidences of that anti-cough exempt of
      medical lapsing they have superior effectiveness to the one of placebo for the
      relief of the cough. The phonoaudiology therapy can benefit patients with
      refractory chronic cough to the pharmacological treatment, over all when
      paradoxical movement of the vocal folds coexists. Final Comments: The boarding to
      multidiscipline has basic paper in the etiological diagnosis and treatment of the
      cough. The otolaryngologist must inform the patients on the risks of the anti
      cough of free sales in order to prevent adverse poisonings and effect, especially
      in children.

PMID- 25991945
TI  - Applicability of the free field Sustained Auditory Attention Ability Test
      (SAAAT).
AB  - INTRODUCTION:  The attention is an underlying neuropsychology function to all the
      cognitive processes. The auditory deficiency compromises the normal development
      of the child, modifying diverse auditory abilities, including the attention.
      OBJECTIVE:  to compare the performance of children in the Test of the Ability of
      Auditory Attention Support, as for the different forms of application (auricular
      phones and free field), sort and, application order. METHOD:  40 children (7
      years old) voluntary with typical development had participated, divided in two
      groups: G1 and G2, composites of 20 children each. The application of the THAAS
      in the G1 if gave first with auricular phones and after that in free field and
      the G2 the process was inverse. The evaluation consisted in: specific
      questionnaire, auditory tests and application of the THAAS. RESULTS:  It did not
      have significant difference how much to the sort. For the THAAS with phones, the
      G1 presented greater amount of errors of carelessness and total punctuation. For
      the THAAS in field it had a significant difference of the G2 for the monitoring
      decrease. How much to the application form, the G1 demonstrated a bigger number
      of errors when it was used phones. The G2 did not demonstrate difference.
      CONCLUSION:  It had viability in the application of the THAAS in Free Field,
      being able to be adopted the same used normative values for the conventional way
      of evaluation.

PMID- 25991946
TI  - Nasal septum perforation in patient with pyoderma gangrenosum.
AB  - INTRODUCTION:  The cocaine is obtained from the leaves of the coca (Erythroxylon
      coca). It can be used in many ways, but the most common is the drug inhalation.
      The Cocaine also causes vasoconstriction at nasal mucous membrane and its chronic
      use can cause necrosis and nasal septum perforation. Pyoderma gangrenosum is an
      uncommon idiopathic disease characterized by ulcerations, usually observed on the
      legs. Its diagnosis is most common an exclusion of others diseases. So far, there
      is no specific treatment based on evidence by randomized controlled trials.
      OBJECTIVE:  Describe the rare association between Pyoderma gangrenosum and
      cocaine. CASE REPORT:  E. A., 27-year-old woman with destruction of nasal septum
      and palate who has been using a big amount of cocaine, been necessary note the
      difference from which disease cause de damage. Final Comments: Also there are
      only three cases of Pyoderma gangrenosum complicated with nasal septum
      perforation in cocaine users.

PMID- 25991947
TI  - Vestibular system paresis due to emergency endovascular catheterization.
AB  - OBJECTIVE:  The objective of this story of case is to describe an uncommon cause
      of associated peripheral Vestibulopathy to the unilateral auditory loss in aged
      patient after catheterization of urgency. Story of case: Patient of the masculine
      sort, 82 years, submitted to the correction of abdominal ragged aneurism of
      aorta, in the intra-operative suffered heart attack acute from the myocardium
      needing primary angioplasty. High after hospital it relates to complaint of
      accented hearing loss to the right and crippling vertigo, without focal
      neurological signals. To the otorhinolaryngological clinical examination it
      presented: Test of Weber lateralized for the left, spontaneous nystagmus for the
      left, marches rocking, has taken normal disbasia and ataxia, index-nose and
      diadochokinesia, Test of Romberg with oscillation without fall and Fukuda with
      lateral shunting line for the right. The audiometric examination evidenced
      deafness to the right and sensorineural loss to the left in sharps, areflexia
      initial to the right in caloric test e, the computerized tomography of the
      secular bones and brainstem, presence of metallic connecting rod crossing the
      right secular bone, from the vein internal jugular vein and bulb jugular vein,
      crossing the posterior, superior and vestibule semicircular canals, projecting
      itself in temporal lobe. The radiological diagnoses was traumatic injury for
      guide to endovascular metallic during catheterization of urgency and the
      behavior, considering that the patient had not compensated the balance, it was
      vestibular rehabilitation. CONCLUSION:  Complaints of giddiness in the aged
      patient must be closely evaluated of its pathological clinical description
      because the antecedents of illnesses and previous treatments, in general, direct
      the diagnostic hypotheses however they can bring unexpected alterations.

PMID- 25991949
TI  - Editorial.

PMID- 25991948
TI  - Fungus ball of the paranasal sinuses: Report of two cases and literature review.
AB  - INTRODUCTION:  Fungal ball of the sinuses is a not invasive infection that if
      characterizes for its chronicity, being the majority related with previous
      endodontic treatment. Affect mainly the breasts to maxillary; even so all the
      breasts can be involved. The main etiological agent is the Aspergillus spp. The
      computed tomography, had to characteristic the radiological presentations,
      suggests the diagnosis that is carried through definitively through
      histopathological analyses. The treatment standard-gold is the sinus surgery with
      average meatal antrostomy. OBJECTIVE:  Reporting two cases of fungal ball of the
      sinuses and to stand out important aspects of this pathology. Story of the Cases:
      Case 1) Patient of the feminine sex, 78 years old, presented itself with
      complaints of face pain has 6 months and previous history of endodontic
      treatment. To the physical examination it was evidenced purulent secretion
      presence in left average meatus. Ray X presented complete veiling of the breasts
      to maxillary left, while the computed tomography showed injury calcified in this
      place. Sinusotomy was become fulfilled that evolved well. Case 2) Patient of the
      feminine sex, 70 years old, looked attendance for history of sinusitis of
      repetition. To the physical examination no particularity was not perceived. The
      computed tomography, as well as the magnetic resonance, detected thickening of
      the mucous wall of the breasts to maxillary left, beyond a calcified mass. It was
      become fulfilled same sequence of treatment and the patient also evolved well.
      FINAL CONSIDERATIONS:  The fungal infection must be considered in the patients
      who if present with chronic sinusitis, that they do not answer to the antibiotic
      use and that they possess history of endodontic manipulation.

PMID- 25991950
TI  - Relationship between vocal symptoms in college students and their possible
      causes.
AB  - INTRODUCTION:  Studies to understand the vocal profile of a population are
      important to plan collective health measures. The prevalence of vocal symptoms
      can be indicative of vocal disorder and must be investigated to support measures
      to prevent vocal diseases. AIM:  To characterize vocal symptoms in college
      students and their possible causes, and to analyze the association between
      hoarseness, vocal fatigue, phlegm, and burning in the throat with the possible
      causes mentioned. METHOD:  Prospective study of 517 students who answered a
      questionnaire about their general heath and vocal symptoms and causes. We used
      the study of proportions, measures of central tendency, and a chi-square test to
      associate the presence of symptoms and possible causes. RESULTS:  Symptoms most
      often mentioned: dry mouth (21%), dry throat (18.2%), phlegm (17.9%). Causes most
      often cited: high respiratory disease (39%), intense voice use (24%), smoking
      (24%). Hoarseness was associated with heavy use of voice and high respiratory
      disease; vocal fatigue with intense voice use, stress, and digestive problems;
      burning in the throat with intensive voice use, high respiratory disease, and
      pollution; phlegm with smoking, and upper respiratory and digestive problems.
      CONCLUSION:  Not only do aspects of health and the voice interfere with its
      production, the external environment and habits influence the vocal symptoms of
      this population as well.

PMID- 25991951
TI  - Correlation between brain injury and dysphagia in adult patients with stroke.
AB  - INTRODUCTION:  In the literature, the incidence of oropharyngeal dysphagia in
      patients with cerebrovascular accident (AVE) ranges 20-90%. Some studies
      correlate the location of a stroke with dysphagia, while others do not.
      OBJECTIVE:  To correlate brain injury with dysphagia in patients with stroke in
      relation to the type and location of stroke. METHOD:  A prospective study
      conducted at the Hospital de Clinicas with 30 stroke patients: 18 women and 12
      men. All patients underwent clinical evaluation and swallowing
      nasolaryngofibroscopy (FEES((r))), and were divided based on the location of the
      injury: cerebral cortex, cerebellar cortex, subcortical areas, and type:
      hemorrhagic or transient ischemic. RESULTS:  Of the 30 patients, 18 had ischemic
      stroke, 10 had hemorrhagic stroke, and 2 had transient stroke. Regarding the
      location, 10 lesions were in the cerebral cortex, 3 were in the cerebral and
      cerebellar cortices, 3 were in the cerebral cortex and subcortical areas, and 3
      were in the cerebral and cerebellar cortices and subcortical areas. Cerebral
      cortex and subcortical area ischemic strokes predominated in the clinical
      evaluation of dysphagia. In FEES((r)), decreased laryngeal sensitivity persisted
      following cerebral cortex and ischemic strokes. Waste in the pharyngeal recesses
      associated with epiglottic valleculae predominated in the piriform cortex in all
      lesion areas and in ischemic stroke. A patient with damage to the cerebral and
      cerebellar cortices from an ischemic stroke exhibited laryngeal penetration and
      tracheal aspiration of liquid and honey. CONCLUSION:  Dysphagia was prevalent
      when a lesion was located in the cerebral cortex and was of the ischemic type.

PMID- 25991952
TI  - Auditory hallucinations in tinnitus patients: Emotional relationships and
      depression.
AB  - INTRODUCTION:  Over the last few years, our Tinnitus Research Group has
      identified an increasing number of patients with tinnitus who also complained of
      repeated perception of complex sounds, such as music and voices. Such
      hallucinatory phenomena motivated us to study their possible relation to the
      patients' psyches. AIMS:  To assess whether hallucinatory phenomena were related
      to the patients' psychosis and/or depression, and clarify their content and
      function in the patients' psyches. METHOD:  Ten subjects (8 women; mean age =
      65.7 years) were selected by otolaryngologists and evaluated by the same
      psychologists through semi-structured interviews, the Hamilton Depression Rating
      Scale, and psychoanalysis interviews. RESULTS:  We found no association between
      auditory hallucinations and psychosis; instead, this phenomenon was associated
      with depressive aspects. The patients' discourse revealed that hallucinatory
      phenomena played unconscious roles in their emotional life. In all cases, there
      was a remarkable and strong tendency to recall/repeat unpleasant
      facts/situations, which tended to exacerbate the distress caused by the tinnitus
      and hallucinatory phenomena and worsen depressive aspects. CONCLUSIONS:  There is
      an important relationship between tinnitus, hallucinatory phenomena, and
      depression based on persistent recall of facts/situations leading to psychic
      distress. The knowledge of such findings represents a further step towards the
      need to adapt the treatment of this particular subgroup of tinnitus patients
      through interdisciplinary teamwork. Prospective.

PMID- 25991953
TI  - Prevalence of tinnitus in workers exposed to noise and organophosphates.
AB  - INTRODUCTION:  Research on the workplace has emphasized the effects of noise
      exposure on workers' hearing, but has not considered the effects of
      agrochemicals. AIM:  To evaluate and correlate the hearing level and tinnitus of
      workers exposed simultaneously to noise and organophosphates in their workplace
      and to measure tinnitus distress on their quality of life. METHOD:  A
      retrospective clinical study. We evaluated 82 organophosphate sprinklers from the
      Sao Paulo State Regional Superintendence who were active in the fight against
      dengue and who were exposed to noise and organophosphates. We performed pure tone
      audiometry and applied the translated THI (Tinnitus Handicap Inventory)
      questionnaire. RESULTS:  Of the sample, 28.05% reported current tinnitus or had
      presented tinnitus, and the workers with tinnitus had an increased incidence of
      abnormal audiometry. The average hearing threshold for the 4-8-kHz frequency
      range of the workers with current tinnitus was higher than that of the others,
      and was most affected at the 4-kHz frequency. The THI score ranged 0-84, with an
      average score of 13.1. Twelve (52.17%) workers had THI scores consistent with
      discrete handicap. CONCLUSION:  There is an increased incidence of abnormal pure
      tone audiometry in workers with tinnitus, and its impact on the workers' quality
      of life was discrete. The correlation between average hearing threshold and
      tinnitus distress was weak.

PMID- 25991954
TI  - Auditory middle latency response in children with learning difficulties.
AB  - INTRODUCTION:  This is an objective laboratory assessment of the central auditory
      systems of children with learning disabilities. AIM:  To examine and determine
      the properties of the components of the Auditory Middle Latency Response in a
      sample of children with learning disabilities. METHODS:  This was a prospective,
      cross-sectional cohort study with quantitative, descriptive, and exploratory
      outcomes. We included 50 children aged 8-13 years of both genders with and
      without learning disorders. Those with disorders of known organic, environmental,
      or genetic causes were excluded. RESULTS AND CONCLUSIONS:  The Na, Pa, and Nb
      waves were identified in all subjects. The ranges of the latency component values
      were as follows: Na = 9.8-32.3 ms, Pa = 19.0-51.4 ms, Nb = 30.0-64.3 ms (learning
      disorders group) and Na = 13.2-29.6 ms, Pa = 21.8-42.8 ms, Nb = 28.4-65.8 ms
      (healthy group). The values of the Na-Pa amplitude ranged from 0.3 to 6.8 iV
      (learning disorders group) or 0.2-3.6 iV (learning disorders group). Upon
      analysis, the functional characteristics of the groups were distinct: the left
      hemisphere Nb latency was longer in the study group than in the control group.
      Peculiarities of the electrophysiological measures were observed in the children
      with learning disorders. This study has provided information on the Auditory
      Middle Latency Response and can serve as a reference for other clinical and
      experimental studies in children with these disorders.

PMID- 25991955
TI  - Assessment of nasal patency after rhinoplasty through the Glatzel mirror.
AB  - INTRODUCTION:  OBJECTIVE evaluation of nasal function is a constant challenge for
      plastic surgeons, otolaryngologists, and allergists. The modified Glatzel mirror
      can evaluate nasal expiratory flow; however, there is little information on this
      method and its use in the measurement of nasal patency after surgical procedures.
      OBJECTIVE:  To compare, in a prospective study, the functional results before and
      after cosmetic rhinoplasty and evaluate the use of the Glatzel mirror as an
      objective method to assess nasal patency. METHODS:  To achieve this objective, we
      analyzed the functional results of surgery through a subjective questionnaire and
      objective evaluation through a modified Glatzel mirror, and evaluated the
      correlation between the 2 methods. Twenty patients (14 women and 6 men) underwent
      aesthetic rhinoplasty using spreader grafts. Pre- and postoperative evaluation
      (90-120 days) included a respiratory quality score (subjective) and modified
      Glatzel mirror test (objective). Subsequently, the Spearman test was used to
      compare the pre- and postoperative subjective and objective data. RESULTS:  The
      subjective evaluation demonstrated a statistical difference between pre- and
      postoperative scores (8 +/- 2 and 9.4 +/- 0.7, P <= 0.001). There was no
      statistical difference in mean nasal patency by modified Glatzel mirror. No
      statistically significant correlation was observed when comparing the modified
      Glatzel mirror values with the subjective scores reported by patients pre- or
      postoperatively. CONCLUSION:  The Glatzel method lacks sensitivity in detecting
      patient-reported improvements in breathing following rhinoplasty. This suggests
      that the method is a poor assessment tool to detect small, post-surgical changes
      in the nasal airways.

PMID- 25991956
TI  - Proposed computerized protocol for epidemiological study of patients undergoing
      microsurgery of the larynx.
AB  - INTRODUCTION:  The merging of medicine with information technology facilitates
      the retrieval of stored data, aiding the conduct of research with greater
      scientific rigor. Studies in the field of otorhinolaryngology, specifically in
      the area of laryngology and voice, are of fundamental importance, since 70% of
      the economically active need their voice to work. OBJECTIVE:  To create a
      computerized protocol of the diseases of the larynx, apply and validate it, and
      use it to evaluate patients undergoing laryngoscopic microsurgery of the larynx.
      METHOD:  We created a database of ENT diseases through a literature review of
      textbooks and scientific articles. Next, we computerized the data and
      incorporated it into the SINPE((c)), creating a master protocol (ENT diseases)
      and a specific protocol (laryngeal diseases). Data were collected prospectively
      from patients undergoing laryngeal microsurgery in the ENT Hospital of Parana.
      The collected data were analyzed with graphs through the SINPE((c)) Analyzer
      module. RESULTS:  We evaluated 245 patients aged 9-79 years, and determined that
      36.61% (93 patients) underwent surgery for the presence of polyps on the vocal
      folds, 12.6% (32) underwent surgery for papillomatosis, and 11.83% (29) underwent
      surgery for intracordal cysts. CONCLUSIONS:  The creation of an electronic
      database of clinical ENT diseases was feasible. We were also able to implement
      and validate the protocol. The database may be released to physicians involved in
      clinical data collection and retrieval of information to conduct scientific
      research in an organized manner. The most common laryngeal disorders identified
      were polyps, papilloma, and intracordal cysts.

PMID- 25991957
TI  - Middle ear resonance in infants: Age effects.
AB  - INTRODUCTION:  The resonant frequency is the probe frequency in which susceptance
      is 0 due to the neutralization of the forces of mass and stiffness components
      that control the middle ear. This frequency can be evaluated by multifrequency
      tympanometry, and the normality value for adults ranges 800-1,200 Hz. Studies
      about resonant frequency in children are scarce. AIM:  Identify the variation of
      the resonant frequency in infants between the first days after birth and the
      third month of life. METHOD:  Prospective study. Thirty newborns were evaluated
      at 2 different times: at the neonatal phase up to 12 days of life, and between 72
      and 84 days of life. In the first evaluation, we carried out otoacoustic
      emissions and identified the resonant frequency, and identified the resonant
      frequency again in the second evaluation. RESULTS:  In the first evaluation, we
      determined a mean resonance value of 250 Hz for both ears, while that in the
      second evaluation was 385 Hz. In both assessments, we found no significant
      differences between the ears. There was a significant difference between the
      first and second evaluation. CONCLUSION:  The middle ear resonant frequency in
      infants is lower in the first days of life due to the influence of the mass
      component. The present study demonstrated that the resonance frequency increased
      in the first months of life.

PMID- 25991958
TI  - Analysis of the masticatory process of asthmatic children: Clinical and
      electromyographic research.
AB  - INTRODUCTION:  The prevalence of asthma has grown considerably in recent decades,
      but some studies have shown stabilization of this trend. The masticatory process
      of asthmatic children may be altered due to asthma-related anatomo-functional
      changes. OBJECTIVE:  The study objective was to determine the clinical and
      electromyographic characteristics of the masticatory process in asthmatic
      children and compare the electrical activities of their masseter and anterior
      temporal muscles (at rest and during maximal voluntary contraction and
      mastication) with those of non-asthmatic children. METHOD:  Case study. Asthmatic
      and non-asthmatic groups, each consisting of 30 children of both sexes between 6
      and 10 years of age, were evaluated. Mastication was evaluated clinically and
      electromyographically in all subjects. RESULTS: The masticatory process did not
      differ significantly between asthmatic and non-asthmatic children. CONCLUSION: 
      Although the masticatory process did not differ significantly between asthmatic
      and non-asthmatic children, the masticatory process of asthmatic children may be
      altered because of anatomical changes of Asthma.

PMID- 25991959
TI  - Real ear unaided gain and its relation with the equivalent volume of the external
      and middle ear.
AB  - INTRODUCTION:  Old age is associated with changes in the characteristics of the
      middle ear transmission system and in external ear resonance, and these carry
      implications for the hearing aid (HA) verification process for which targets and
      measures of the real ear insertion gain (REIG) are used. AIM:  To compare the
      real ear unaided gain (REUG) and the equivalent volumes of the external ear
      (VeqEE) and the middle ear (VeqME) between elderly and adult patients. METHODS: 
      This is a retrospective study in which the medical records of 28 elderly patients
      (aged between 61 and 102 years, average hearing thresholds between 38.75 and 85
      dB HL) and 23 adult patients (aged 20-59, mean hearing thresholds between 31.25
      and 116.25 dB HL) with bilateral sensorineural hearing loss and no history of
      middle ear abnormalities were analyzed. Immittance measurements (VeqEE, VeqME,
      and pressure of the peak of maximum compliance) and the REUG (frequency and
      amplitude of the primary peak) were recovered for a total of 40 ears. These data
      were compared between elderly and adults as well as between men and women, using
      Student's t test. Correlations (Pearson) between immittance and REUG data were
      also verified. RESULTS:  No statistically significant differences (p < 0.01) were
      found for immittance and REUG data between elderly and adults, or between men and
      women. A negative and weak but significant correlation was observed between the
      REUG primary peak and VeqEE. CONCLUSION:  Hearing aid verification can be
      performed with target and measures of the REIG in the elderly population.

PMID- 25991960
TI  - Remote hearing aid fitting: Tele-audiology in the context of Brazilian Public
      Policy.
AB  - INTRODUCTION:  Currently, the Brazilian government has certificated nearly 140
      specialized centers in hearing aid fittings through the Brazilian National Health
      System (SUS). Remote fitting through the Internet can allow a broader and more
      efficient coverage with a higher likelihood of success for patients covered by
      the SUS, as they can receive fittings from their own homes instead of going to
      the few and distant specialized centers. AIM:  To describe a case of remote
      fitting between 2 cities, with revision of the literature. METHOD: Computer
      gears, a universal interface, and hearing aids were used. CASE STUDY: An
      audiologist located in a specialized center introduced a new hearing aid and its
      fitting procedure to a remote center (200 km away). The specialized center helped
      the remote center in fitting a hearing aid in 2 patients, and performed fitting
      in one of its own patients. The whole process was done through the Internet with
      audio and video in real time. RESULTS: Three patients were fitted remotely. Three
      audiologists were remotely trained on how to fit the hearing aids. CONCLUSIONS: 
      Remote fitting of hearing aids is possible through the Internet, as well as
      further supplying technical training to a remote center about the fitting
      procedures. Such a technological approach can help the government advance public
      policies on hearing rehabilitation, as patients can be motivated about
      maintaining their use of hearing aids with the option to ask for help in the
      comfort of their own homes.

PMID- 25991961
TI  - Comparative study of continuous lateral osteotomy and microperforating osteotomy
      in patients undergoing primary rhinoplasty.
AB  - INTRODUCTION:  Lateral osteotomies play an important role in rhinoplasty and can
      be performed with different techniques. OBJECTIVE:  To compare the results of
      narrowing of the nasal dorsum and base through 2 types of lateral osteotomy:
      continuous and microperforating. METHOD:  We selected 74 patients undergoing
      rhinoplasty: 37 patients underwent lateral continuous osteotomy and the other 37
      underwent microperforating osteotomy, all performed by the same surgeon. We
      analyzed frontal photography from the pre- and post-operative (6 months) periods,
      evaluating the width of the nasal dorsum and base. This was a retrospective
      study. RESULTS AND CONCLUSION:  Using Student's t-test, statistical analysis
      concluded that there was a statistically significant difference in the post
      operative narrowing of the nasal dorsum and base following both osteotomy
      techniques, and there was no statistically significant difference between the 2
      techniques.

PMID- 25991962
TI  - Prelingual deafness: Benefits from cochlear implants versus conventional hearing
      aids.
AB  - INTRODUCTION:  The majority of patients with hearing loss, including those with
      severe hearing loss, benefits from the use of hearing aids. The cochlear implant
      is believed to achieve better results in a child with hearing loss in cases where
      the severity of disability renders hearing aids incapable of providing adequate
      sound information, as they require sufficient cochlear reserve so that acoustic
      detention occurs. OBJECTIVE:  To assess if cochlear implants provide more benefit
      than conventional hearing aids in prelingually deaf patients. SUMMARY OF THE
      FINDINGS:  The study was a systematic review of scientific papers selected by a
      search of the SciELO, Cochrane, MEDLINE, and LILACS-BIREME databases. Among the
      2169 articles found, 12 studies proved relevant to the issue and presented an
      evidence strength rating of B. No publications rated evidence strength A. Seven
      of the studies analyzed were prospective cohorts and 5 were cross-sectional
      studies. CONCLUSION: Based on several studies, cochlear implants were
      demonstrated to be the best current alternative for bilateral severe or profound
      hearing loss, achieving better results in speech perception and development in
      prelingual children when compared to conventional hearing aids.

PMID- 25991963
TI  - Nose tip refinement using interdomal suture in caucasian nose.
AB  - INTRODUCTION:  Refinement of the nose tip can be accomplished by a variety of
      techniques, but currently, the use of sutures in the nasal tip with conservative
      resection of the alar cartilage is the most frequently recommended approach.
      OBJECTIVE:  To classify the nasal tip and to demonstrate the interdomal suture
      applied to nasal tip refinement in the Caucasian nose, as well as to provide a
      simple and practical presentation of the surgical steps. METHOD:  Development of
      surgical algorithm for nasal tip surgery: 1. Interdomal suture (double binding
      suture), 2. Interdomal suture with alar cartilage weakening (cross-hatching), 3.
      Interdomal suture with cephalic removal of the alar cartilage (McIndoe technique)
      based on the nasal tip type classification. This classification assesses the
      interdomal distance (angle of domal divergence and intercrural distance), domal
      arch width, cartilage consistency, and skin type. Interdomal suture is performed
      through endonasal rhinoplasty by basic technique without delivery (Converse
      Diamond technique) under local anesthesia. CONCLUSION:  This classification is
      simple and facilitates the approach of surgical treatment of the nasal tip
      through interdomal suture, systematizing and standardizing surgical maneuvers for
      better refinement of the Caucasian nose.

PMID- 25991964
TI  - Rehabilitation of oropharyngeal dysphagia in children with cerebral palsy: A
      systematic review of the speech therapy approach.
AB  - INTRODUCTION:  There are an estimated 30,000-40,000 new cases of cerebral palsy
      per year in Brazil. Motor disorders caused by cerebral palsy can lead to
      dysphagia as they may alter the preparatory, oral, pharyngeal, and esophageal
      phases. AIM: To identify existing rehabilitation methods of swallowing disorders
      in cerebral palsy, with emphasis on the pursuit of research using the Bobath
      concept, the Castillo Morales concept, oral sensorimotor therapy, and continuing
      education. SUMMARY OF THE FINDINGS: We performed a systematic review of the
      medical and speech therapy literature on the rehabilitation of oropharyngeal
      dysphagia in children with cerebral palsy spanning 1977-2010 and from all
      languages and nations. Among the 310 articles retrieved, only 22 (7.09%)
      addressed therapeutic rehabilitation of oropharyngeal dysphagia in children with
      cerebral palsy. Of the 22 reports, 12 (54.5%) were from Canada, 3 (13.6%) were
      from Japan, 2 (9%) were from Brazil, 2 (9%) were from Germany, 1 (4.5%) was from
      the USA, 1 (4.5%) was from the United Kingdom, and 1 (4.5%) was from Poland. Of
      these reports, 63.6% used oral sensorimotor therapy as a therapeutic method,
      36.3% reported continuing education as a therapeutic approach, and only 18.1% and
      9% used the Bobath concept and Castillo Morales concept, respectively.
      CONCLUSION: Even with a constantly increasing cerebral palsy population, few
      studies include (re)habilitation in the treatment of oropharyngeal dysphagia in
      these children.

PMID- 25991965
TI  - Bone-anchored hearing aid (BAHA): indications, functional results, and comparison
      with reconstructive surgery of the ear.
AB  - INTRODUCTION:  The bone-anchored hearing aid (BAHA) is a bone conduction hearing
      device that transmits sound directly into the inner ear. It is mainly used in
      patients with conductive hearing loss associated with aural atresia, but it is
      also used in those with mixed and sensorineural hearing loss. GOALS:  To review
      the main indications for BAHA, to analyze the audiometric results and its
      benefits for patients and compare them with other treatment modalities, and to
      compare the literature data with our sample of 13 patients. METHOD:  The research
      was performed using a database covering works in English, Spanish, and
      Portuguese, with no limitations in the years when the procedures were performed.
      We compared the literature data with our results for the 13 patients who
      underwent BAHA implantation between the years 2000 and 2009. RESULTS:  Most of
      the studies showed that BAHA has great advantages over reconstructive surgery in
      terms of hearing results, complications, and disease recurrence. The
      postoperative results for our 13 patients were satisfactory and comparable with
      the results from the literature, with closure of the air-bone gap in 7 patients
      and achieving an air-bone gap of 10 dB in 6 patients. No postoperative
      complications were observed. CONCLUSION:  BAHA is a better treatment option than
      reconstructive surgery for patients with bilateral deafness. It is a relatively
      simple surgical procedure with few complications and good hearing results. Recent
      studies have examined its use in conductive and unilateral sensorineural hearing
      loss.

PMID- 25991966
TI  - Cochlear implantation in patient with Dandy-walker syndrome.
AB  - INTRODUCTION:  Dandy Walker Syndrome is a congenital abnormality in the central
      nervous system, characterized by a deficiency in the development of middle
      cerebelar structures, cystic dilatation of the posterior pit communicating with
      the fourth ventricle and upward shift of the transverse sinuses, tentorium and
      dyes. Among the clinical signs are occipital protuberances, a progressive
      increase of the skull, bowing before the fontanels, papilledema, ataxia, gait
      disturbances, nystagmus, and intellectual impairment. OBJECTIVES:  To describe a
      case of female patient, 13 years old with a diagnosis of this syndrome and
      bilateral hearing loss underwent cochlear implant surgery under local anesthesia
      and sedation. CASE REPORT:  CGS, 13 years old female was referred to the
      Otolaryngological Department of Otolaryngology Institute of Parana with a
      diagnosis of "Dandy-Walker syndrome" for Otolaryngological evaluation for
      bilateral hearing loss with no response to the use of hearing aids. Final
      Comments: The field of cochlear implants is growing rapidly. We believe that the
      presence of Dandy-Walker syndrome cannot be considered a contraindication to the
      performance of cochlear implant surgery, and there were no surgical complications
      due to neurological disorders with very favorable results for the patient who
      exhibits excellent discrimination. It has less need for lip reading with
      improvement in speech quality.

PMID- 25991967
TI  - Extramedullary plasmacytoma of the larynx.
AB  - INTRODUCTION:  The extramedullary plasmocytoma is one of the localized forms of
      malignancy of the plasma cells, which has multiple myeloma main diagnosis. Its
      main site to the head and neck, but with a rare presentation in the larynx.
      OBJECTIVE:  To describe a case of extramedullary plasmocytoma of the larynx, with
      literature review. CASE REPORT:  Patient female, 49, referring to intermittent
      dysphonia for 01 years with progressive worsening associated with vocal fatigue
      and vocal effort, with reddish lesion, smooth edges fold left ventricular
      endoscopy. Being subjected to excisional biopsy diagnosed with extramedullary
      histopathological plasmocytoma. CONCLUSION:  Extramedullary Plasmocytoma must be
      considered in the differential diagnosis of rare tumors of the larynx. It is
      essential after the diagnosis of multiple myeloma research and a "follow up"
      appropriate.

PMID- 25991968
TI  - Partial glossectomy as an auxiliary method to orthodontic treatment of
      dentofacial deformity.
AB  - INTRODUCTION:  macroglossia is a condition which influences the size and shape of
      the teeth employed due to the forces on teeth. OBJECTIVE:  To establish bases for
      the indication of partial glossectomy associated with orthodontic treatment and
      surgical dento-facial deformity in patients without tumors and Down syndrome as a
      cause of macroglossia. CASE REPORTS:  Three patients underwent orthognathic
      surgery associated with partial glossectomy under general anesthesia. All
      patients had macroglossia relative and underwent clinical assessment taking into
      account the respiratory function, swallowing and speech deficits and radiological
      evaluation. The technique used consist of segmental resection along the median
      raphe of the tongue and suture by planes. We used rigid skeletal fixation with
      titanium plates and screws so that patients could stay without intermaxillary
      block in the immediate postoperative period. Were followed over five years. The
      symptoms regressed completely and all skeletal segments remained stable.
      DISCUSSION:  The decision to refer the patient to partial glossectomy should be
      based on the volume of the language, mobility, position, function, symptoms,
      speech intelligibility, skeletal anterior open bite, interference in orthodontic
      treatment, drooling, swallowing and tongue trauma applicant.

PMID- 25991969
TI  - Editorial.

PMID- 25991970
TI  - Evaluation of quality of life pre- and post-vestibular rehabilitation in patients
      with benign paroxysmal positional vertigo associated with Meniere's disease.
AB  - INTRODUCTION:  Vertigo is a symptom that impacts the patients' quality of life
      and may force them to cease performing activities of daily living. Here, we
      discuss benign paroxysmal positional vertigo (BPPV) and Meniere's disease (MD),
      which show exacerbated symptoms when they appear in association. Vestibular
      rehabilitation (VR) is an effective treatment in reducing vertigo, especially in
      conjunction with other therapies. AIM:  To evaluate the quality of life of
      patients with BPPV and MD before and after VR. METHOD:  We conducted a
      descriptive observational qualitative and quantitative case study with 12
      patients aged 35 to 86 years. All patients diagnosed with BPPV and MD received
      treatment in the ENT clinic. The Brazilian DHI questionnaire, which assesses the
      quality of life with a focus on physical, emotional, and functional aspects, was
      used for data collection, and was completed by patients before the first session
      and after the fifth session of VR. Data were tested using the Shapiro-Wilk
      normality test, followed by Wilcoxon, Friedman, and Spearman correlation tests (p
      < 0.05). RESULTS:  There were significant improvements in scores for all aspects,
      with median changes ranging from 12 to 0 in the physical, 6 to 1 in the
      emotional, and 11 to 1 in the functional aspect. There were no correlations
      between the scores and sample characteristics. CONCLUSION:  VR was an effective
      method for the treatment of patients with BPPV and MD; it improves quality of
      life and shows the maximal influence on physical aspect scores, regardless of age
      or gender.

PMID- 25991971
TI  - Epidemiological profile of 277 patients with facial fractures treated at the
      emergency room at the ENT Department of Hospital do Trabalhador in Curitiba/PR,
      in 2010.
AB  - INTRODUCTION:  Epidemiological studies that focus on facial injuries are of great
      interest for the knowledge of occurrence and severity of presentation. AIM:  To
      study the epidemiological profile of 277 patients who suffered facial fractures
      at the Hospital do Trabalhador (HT), with an emphasis on variables such as sex,
      age, cause, and anatomical sites of fractures, comparing the clinical findings
      with other studies. METHOD:  Retrospective nonrandomized chart review of 277
      patients who were treated at HT by the ENT service during the full year 2010,
      victims of facial fractures. RESULTS:  Of 277 patients, 74.72% were male and
      25.27% female (ratio 3:1). According to age, the fractures were distributed as
      follows: 0-9 years: 4.69%, 10-19 years: 17.32%, 20-29 years: 23.82%, 30-39 years:
      20.21%, 40-49 years: 16.24%, 50-59 years: 10.83%, 60-69 years: 3.97%, and 60-79
      years: 2.88%. The cause of trauma was most frequently interpersonal violence,
      36.45%, followed by falls, 23.09%, and motor vehicle crashes with 17.32%.
      Regarding location, nasal fracture was the most common, with 44.75%, followed by
      the mandible, 14.32%, orbit, 12.78%, maxillary, 12.02%, zygomatic, 9.97%, 3.32%
      and front Le Fort 2.88%. CONCLUSION:  The patients were mostly males, aged 21-30
      years, victims of aggression with the most commonly fractured bone being the
      nose. The adoption of personal and public strategies and measures may prevent
      facial fractures.

PMID- 25991972
TI  - Rhinoplasty and facial asymmetry: Analysis of subjective and anthropometric
      factors in the Caucasian nose.
AB  - INTRODUCTION:  Anthropometric proportions and symmetry are considered
      determinants of beauty. These parameters have significant importance in facial
      plastic surgery, particularly in rhinoplasty. As the central organ of the face,
      the nose is especially important in determining facial symmetry, both through the
      perception of a crooked nose and through the determination of facial growth. The
      evaluation of the presence of facial asymmetry has great relevance
      preoperatively, both for surgical planning and counseling. AIM/OBJECTIVE:  To
      evaluate and document the presence of facial asymmetry in patients during
      rhinoplasty planning and to correlate the anthropometric measures with the
      perception of facial symmetry or asymmetry, assessing whether there is a higher
      prevalence of facial asymmetry in these patients compared to volunteers without
      nasal complaints. METHODS:  This prospective study was performed by comparing
      photographs of patients with rhinoplasty planning and volunteers (controls), n =
      201, and by evaluating of anthropometric measurements taken from a line passing
      through the center of the face, until tragus, medial canthus, corner side wing
      margin, and oral commissure of each side, by statistical analysis (Z test and
      odds ratio). RESULTS:  None of the patients or volunteers had completely
      symmetric values. Subjectively, 59% of patients were perceived as asymmetric,
      against 54% of volunteers. Objectively, more than 89% of respondents had
      asymmetrical measures. Patients had greater RLMTr (MidLine Tragus Ratio)
      asymmetry than volunteers, which was statistically significant.
      DISCUSSION/CONCLUSION:  Facial asymmetries are very common in patients seeking
      rhinoplasty, and special attention should be paid to these aspects both for
      surgical planning and for counseling of patients.

PMID- 25991973
TI  - Profile of cochlear implant users of the city of Manaus.
AB  - INTRODUCTION:  The cochlear implant is a device that is intended to substitute
      for the function of cochlear hair cells, electrically stimulate auditory nerve
      fibers, and contribute to the perception of speech sounds. However, the surgical
      procedure alone is not enough for the user to achieve favorable results in
      habilitation/rehabilitation. OBJECTIVE:  To characterize the patients from Manaus
      who have received cochlear implants based on the criteria for surgery. METHODS: 
      We conducted a retrospective cross-sectional study of 15 cases and recorded
      etiological aspects of deafness, age, gender, duration of implant use, use of
      hearing aids, and participation in individual therapy. Data were recorded in a
      protocol designed specifically for this purpose. All patients were natives of
      Manaus. RESULTS:  The leading etiological aspect was ototoxicity associated with
      prematurity in newborns undergoing treatment in the neonatal intensive care unit.
      The age at surgery is carefully observed in the evaluation of implant centers, as
      well as if the candidate is pre-or post-lingual. In this study, 73% of patients
      were pre-lingual and did not benefit from hearing aids. As to the degree and type
      of hearing loss, 93% had audiological reports indicating profound bilateral
      sensorineural hearing loss and 7% had severe bilateral sensorineural hearing
      loss. This latter finding confirmed one of the basic principles of implant
      placement. CONCLUSION:  This study allowed us to verify that there are reduced
      number of cochlear implant recipients in Manaus, but they have met the criteria
      required by implant centers located in other states of Brazil.

PMID- 25991974
TI  - Quality of life and deglutition after total laryngectomy.
AB  - INTRODUCTION:  Total laryngectomy creates deglutition disorders and causes a
      decrease in quality of life Aim: To describe the impact of swallowing and quality
      of life of patients after total laryngectomy. METHOD:  A case series study.
      Patients completed a Swallowing and Quality of Life questionnaire composed of 44
      questions assessing 11 domains related to quality of life (burden, eating
      duration, eating desire, frequency of symptoms, food selection, communication,
      fear, mental health, social functioning, sleep, and fatigue). The analysis was
      performed using descriptive statistics, including measures of central tendency
      and variability. RESULTS:  The sample comprised 15 patients who underwent total
      laryngectomy and adjuvant radiotherapy. Of these, 66.7% classified their health
      as good and 73% reported no restrictions on food consistency. The domains
      "communication" and "fear" represented severe impact and "eating duration"
      represented moderate impact on quality of life. The items with lower scores were:
      longer time to eat than others (domain "eating duration"), cough and cough to
      remove the liquid or food of the mouth when they are stopped (domain "symptom
      frequency"), difficulties in understanding (domain "communication") and fear of
      choking and having pneumonia (domain "fear"). CONCLUSION:  After total
      laryngectomy, patients report that swallowing issues have moderate to severe
      impact in "communication," "fear," and "eating duration" domains.

PMID- 25991975
TI  - Vestibular schwannoma: 825 cases from a 25-year experience.
AB  - INTRODUCTION:  Acoustic nerve tumors have been recognized as a clinico-pathologic
      entity for at least 200 years, and they represent 90% of cerebellopontine angle
      diseases. Histologically, the tumors are derived from Schwann cells of the myelin
      sheath, with smaller tumors consisting of elongated palisade cells, while in
      large tumors, cystic degeneration can be found in the central areas, possibly due
      to deficient vascularization. We retrospectively reviewed 825 cases of vestibular
      schwannomas, reported between January 1984 and August 2006, in which the patients
      underwent surgery to remove the tumor. OBJECTIVE:  To evaluate signs, symptoms,
      aspects of clinical diagnosis, including the results of audiological and imaging
      studies, and surgical techniques and complications. METHODS:  A retrospective
      chart review. The medical records of all patients undergoing surgical treatment
      for schwannoma during the period indicated were reviewed. RESULTS AND CONCLUSION:
      Hearing loss was the first symptom reported in almost all cases, and tumor size
      was not proportional to the impairment of the auditory threshold. The surgical
      techniques allowed safe preservation of facial function. In particular, the
      retrolabyrinthine route proved useful in small tumors, with 50% preservation of
      hearing.

PMID- 25991976
TI  - Cochlear implants: our experience and literature review.
AB  - INTRODUCTION:  Cochlear Implants are important for individuals with severe to
      profound bilateral sensorineural hearing loss. OBJECTIVE:  Evaluate the
      experience of cochlear implant center of Otorhinolaryngology through the analysis
      of records of 9 patients who underwent cochlear implant surgery. METHODS:  This
      is a retrospective study performed with the patients records. Number
      0191.0.107.000-11 ethics committee approval. We evaluated gender, etiology, age
      at surgery, duration of deafness, classification of deafness, unilateral or
      bilateral surgery, intraoperative and postoperative neural response and impedance
      of the electrodes in intraoperative and preoperative tests and found those that
      counter-indicated surgery. RESULTS:  There were 6 pediatric and 3 adult patients.
      Four male and 5 female. Etiologies: maternal rubella, cytomegalovirus,
      ototoxicity, meningitis, and sudden deafness. The age at surgery and duration of
      deafness ranged from 2-46 years and 2-18 years, respectively. Seven patients were
      pre-lingual. All had profound bilateral PA. There were 7 bilateral implants.
      Intraoperative complications: hemorrhage. Complications after surgery: vertigo
      and internal device failure. In 7 patients the electrodes were implanted through.
      Telemetry showed satisfactory neural response and impedance. CT and MRI was
      performed in all patients. We found enlargement of the vestibular aqueduct in a
      patient and incudomalleolar malformation. CONCLUSION:  The cochlear implant as a
      form of auditory rehabilitation is well established and spreading to different
      centers specialized in otoaudiology. Thus, the need for structured services and
      trained professionals in this type of procedure is clear.

PMID- 25991977
TI  - Limits on quality of life in communication after total laryngectomy.
AB  - INTRODUCTION:  Among people affected by cancer, the impairment of quality of life
      of people affected by cancer can cause have devastating effects. The self-image
      of patients after post-laryngectomyzed patients may be find themselves
      compromised, affecting the quality of life in this population. OBJECTIVE:  To
      characterize quality of life in related to communication in people who have
      undergone went total laryngectomy surgery. METHODS:  This is an observational
      study, with a cross-sectional and descriptive series. Design of series study. The
      sample were comprised 15 patients interviewed the period from January to February
      of 2011. We used the Quality Protocol for Life Communication in Post-laryngectomy
      adapted from Bertocello (2004); which this questionnaire contains 55 questions.
      The protocol was organized from the nature of using responses classified as
      positive and negative aspects, proposals in with respect to five 5 communication
      domains: family relationships, social relationships, personal analysis;
      morphofunctional aspect, and use of writing. To promote and guarantee the
      autonomy of the respondents, was examiners made use of used assistive technology
      with the Visual Response Scale. RESULTS:  The responses that total laryngectomy
      compromises the quality of life in communication amounted to 463 occurrences
      (65.7%), and that who responses suggesting good quality of life were represented
      with amounted to 242 occurrences (34.3%), from a total of 705
      occurrencesresponses. From Among the five 5 Communication domains, four 4 had
      percentages of above 63% for occurrences of negative content for impact on
      communication. Appearance Morphofunctional appearance gave the had the highest
      percentage of negative content, amounting to 77.3% of cases. CONCLUSIONS:  The
      results showed important limitations of a personal and social nature due to poor
      communication with their peers. Thus, there is a need for multidisciplinary
      interventions that aim to minimize the entrapment of negative impact on these
      people communication among these patients.

PMID- 25991978
TI  - Respiratory muscle strength in asthmatic children.
AB  - INTRODUCTION:  Changes in the respiratory system of asthmatics are also due to
      the mechanical disadvantage caused by the increased airway resistance. OBJECTIVE:
      The study aims to evaluate the respiratory muscle strength and nutritional
      status of asthmatic children. METHOD:  This is a prospective descriptive and
      transversal study with 50 children aged 7 to 12 years, who were placed into 2
      groups, asthmatic and non-asthmatic. Respiratory muscle strength was evaluated on
      the basis of maximal inspiratory pressure (MIP) and maximal expiratory pressure
      (MEP). The nutritional status was evaluated by measuring the anthropometric data,
      including height, weight, and body mass index (BMI). The findings were subjected
      to analysis of variance, chi-square, and Student's t test, and p-values < 0.05
      was considered statistically significant. RESULTS:  In our comparisons, we
      observed statistically significantly lower values for age, weight, and height in
      asthmatic patients: 8.52 +/- 1.49 years, 30.62 +/- 7.66 kg, and 129.85 +/- 10.24
      cm, respectively, vs. non-asthmatic children(9.79 +/- 1.51 years, 39.92 +/- 16.57
      kg, and 139.04 +/- 11.62 cm, respectively). There was no significant increase in
      MIP and MEP between the groups: MIP was -84.96 +/- 27.52 cmH2O for the asthmatic
      group and -88.56 +/- 26.50 cmH2O for the non-asthmatic group, and MEP was 64.48
      +/- 19.23 cmH2O for asthmatic children and +66.72 +/- 16.56 cmH2O for non
      asthmatics. CONCLUSION:  There was no statistically significant difference
      between groups, but we observed that MIP and MEP were slightly higher in the non
      asthmatic group than in the asthmatic group.

PMID- 25991979
TI  - Electronic data collection for the analysis of surgical maneuvers on patients
      submitted to rhinoplasty.
AB  - INTRODUCTION:  In the health field, computerization has become increasingly
      necessary in professional practice, since it facilitates data recovery and
      assists in the development of research with greater scientific rigor. OBJECTIVE: 
      the present work aimed to develop, apply, and validate specific electronic
      protocols for patients referred for rhinoplasty. METHODS:  The prospective
      research had 3 stages: (1) preparation of theoretical data bases; (2) creation of
      a master protocol using Integrated System of Electronic Protocol (SINPE((c)));
      and (3) elaboration, application, and validation of a specific protocol for the
      nose and sinuses regarding rhinoplasty. RESULTS:  After the preparation of the
      master protocol, which dealt with the entire field of otorhinolaryngology, we
      idealized a specific protocol containing all matters related to the patient. In
      particular, the aesthetic and functional nasal complaints referred for surgical
      treatment (i.e., rhinoplasty) were organized into 6 main hierarchical categories:
      anamnesis, physical examination, complementary exams, diagnosis, treatment, and
      outcome. This protocol utilized these categories and their sub-items: finality;
      access; surgical maneuvers on the nasal dorsum, tip, and base; clinical evolution
      after 3, 6, and 12 months; revisional surgery; and quantitative and qualitative
      evaluations. CONCLUSION:  The developed electronic-specific protocol is feasible
      and important for information registration from patients referred to rhinoplasty.

PMID- 25991980
TI  - Pharyngeal swallowing phase and chronic cough.
AB  - INTRODUCTION:  The act of swallowing depends on a complex and dynamic process
      which uses common structures to the act of breathing; respiratory problems can
      cause swallowing difficulties. AIM:  To assess the swallowing pharyngeal phase in
      patients with chronic cough. METHOD:  Retrospective study with 15 patients of
      both genders, patients with chronic cough and risk factors for aspiration defined
      by the pneumologic diagnosis. The patients were submitted to anamnesis on
      complaints related to swallowing, chewing and breathing, or related to food and
      to videofluoroscopic examination. RESULTS:  It was observed that 33.3% had normal
      and functional swallowing, being the last one of most prevalence. The mild
      dysphagia was observed in 20% of the patients, the mild to moderate dysphagia in
      6.7% of them. In relation to the Rosenbek scale, 73.3% of patients presented
      degree 1, 6.7% presented degrees 2 and 3, and 13.3% presented degree 8. The most
      found pathology was the chronic cough with 40%, followed by asthma with 20%;
      69.2% of patients presented stasis and of these, five used protection maneuvers,
      of these, seven were effective and only three were used in the presence of
      stasis. The most used maneuver was the multiple swallowing, being effective in
      100%. CONCLUSION:  There are peculiarities in the patients' swallowing with
      chronic cough that, although not presenting complaints relating to swallowing, it
      presents an important aspiration risk due to the presence of changes in breathing
      pattern that can intervene in the coordination between breathing and swallowing,
      which is essential to protect the lower airway.

PMID- 25991982
TI  - Evoked otoacoustic emissions in workers exposed to noise: A review.
AB  - INTRODUCTION:  The otoacoustic emissions test is an essential tool in the
      evaluation of auditory function, since it allows the early detection of cochlear
      damage of occupational origin. OBJECTIVE:  To present a review of the literature
      and analyze the effectiveness of the clinical application of the otoacoustic
      emissions test in workers exposed to noise. METHODS:  A bibliographical search
      covering a period of 10 years was performed in the Virtual Health Library
      including published articles in national and international journals indexed in
      the internationally recognized databases for the health sciences, LILACS, SCIELO,
      and MEDLINE, using the terms "otoacoustic emissions" and "occupational exposure."
      The type of published article (national/international), the type and intensity of
      the stimulus most commonly used for the evoked otoacoustic emissions, the gender
      and age of the subjects, and the conclusions from the retrospective studies were
      all taken into consideration. RESULTS AND CONCLUSIONS:  A total of 19 articles
      were analyzed, 7 national and 12 international, covering subjects from 17 to 77
      years of age, mostly men. The type of stimulus most commonly used for the evoked
      otoacoustic emissions was the distortion method (12). Through this review, we
      have concluded that testing of evoked otoacoustic emissions in workers exposed to
      noise is an important tool in the early diagnosis of noise-induced cochlear
      hearing disorders.

PMID- 25991981
TI  - Prevalence of noise-induced hearing loss in drivers.
AB  - INTRODUCTION:  Work-related hearing loss is one of the most common occupational
      illness progresses over the years of noise exposure associated with the work
      environment, may cause damage to undertake physical activity, the individual's
      physiological and mental besides causing hearing damage irreversible interfering
      with communication and quality of life. With high prevalence of male evaluates
      which is the second leading cause of hearing loss. Since there is no medical
      treatment for this type of hearing loss, it is evident the importance of
      preventive and conferences aimed at preserving hearing and health as a whole.
      OBJECTIVE:  To assess the prevalence of hearing loss in audiometry admission of
      drivers. METHODS:  Retrospective study. By 76 charts of professional drivers in
      leased transport companies. We analyzed data from specific interview and pure
      tone audiometry. RESULTS:  The prevalence of abnormal tests was 22.36% with the
      lowest thresholds for tritonal average of 3,000, 4,000 and 6,000 Hz. The higher
      the age, the higher thresholds. CONCLUSION:  This study has highlighted the
      occurrence of hearing in the absence of complaints. Considering that PAIR is
      preventable, justifies the importance of coordinated and multidisciplinary
      involving not only health teams and safety, but also the institutions involved in
      preserving the health of workers, as the team SESMET, unions or prosecutors.

PMID- 25991983
TI  - Laryngeal leishmaniasis.
AB  - INTRODUCTION: Leishmaniasis is classified into three clinical presentations:
      visceral, coetaneous and mucocutaneous. The latter is usually secondary to
      hematogenous spread after months or years of skin infection and can manifest as
      infiltrative lesions, ulcerated or vegetating in nose, pharynx, larynx and mouth,
      associated or not with ganglionics infarction. Laryngeal involvement is part of
      the differential diagnosis of lesions in this topography as nonspecific chronic
      laryngitis, granulomatosis and even tumors of the upper aerodigestive tract
      presenting atypical evolution. Sometimes it is difficult for the correct
      diagnosis of Leishmaniasis, with description of cases in the literature were
      conducted improperly. OBJECTIVE: The objective of this study is to report a case
      of laryngeal Leishmaniasis addressing the difficulty of diagnosis, complications
      and treatment applied. CASE REPORT: A patient with pain throat, dysphagia,
      odynophagia, dysphonia and weight loss, with no improvement with symptomatic
      medication. At telelaringoscopy, infiltrative lesion showed nodular supraglottis.
      He underwent a tracheotomy for airway obstruction and biopsy with
      immunohistochemical study for a definitive diagnosis of laryngeal Leishmaniasis.
      The patient was referred to the infectious diseases that initiated treatment with
      N-methylglucamine antimoniate with satisfactory response to therapy. Final
      Comments: Faced with a clinical suspicion of granulomatous diseases, it is
      essential to follow protocol laboratory evaluation associated with histological
      injury, to get a precise definition etiological without prolonging the time of
      diagnosis. Medical treatment for mucosal Leishmaniasis, recommended by the World
      Health Organization, was adequate in the case of laryngeal disorders, with
      complete resolution of symptoms.

PMID- 25991984
TI  - Severe complication of posterior nasal packing: Case Report.
AB  - INTRODUCTION:  Severe Epistaxis is common in patients with head trauma,
      especially when associated with multiple fractures of the face and skull base.
      Several methods of controlling bleeding that can be imposed. The anterior nasal
      tapenade associated with posterior Foley catheter is one of the most widespread,
      and the universal availability of necessary materials or their apparent ease of
      execution. METHODS:  Case report on control of severe epistaxis after severe TBI,
      with posterior nasal packing by Foley catheter and control tomography showing
      multiple fractures of the skull base and penetration of the probe into the brain
      parenchyma. CONCLUSION:  This is a rare but possible complication in the
      treatment of severe nose bleeds associated with fracture of the skull base. This
      brief report highlights risks related to the method and suggests some care to
      prevent complications related through a brief literature review.

PMID- 25991985
TI  - Recurrence of atypical fibroxanthoma. Diagnosis and treatment.
AB  - INTRODUCTION:  The soft tissue sarcomas (SPM) accounts for only 1% of malignant
      tumors of the adult population. The SPM is the most frequent malignant fibrous
      histiocytoma (MFH) that exhibits behavior characterized by the tendency to
      invasion of adjacent tissue and metastatic spread early. One of its variants is
      the atypical fibroxanthoma (FA). OBJECTIVE:  To describe a case of probable
      recurrence of AF underwent surgical treatment and presentation of a literature
      review. CASE REPORT:  Patient female, 63 years, presenting with a mass in the
      face about four inches and a history of prior resection of the lesion in the same
      topography. The patient underwent surgical resection with a diagnosis of AF.
      CONCLUSION:  The FA is a rare tumor histological diagnosis difficult. The correct
      histological diagnosis and patient follow-up are essential.

PMID- 25991986
TI  - Editorial.

PMID- 25991987
TI  - Prevalence of otorhinolaryngologic diagnoses in the pediatric emergency room.
AB  - INTRODUCTION:  Fever and pain, which are very common in ear, nose, and throat
      pathologies, are among the most frequent complaints recorded during emergency
      room pediatric patient treatment. Most of time, the pediatricians are called on
      to evaluate otorhinolaryngology disorders that requires specialist assessment.
      AIM:  To determine the prevalence of otorhinolaryngologic diagnoses in a
      pediatric population in a reference hospital in the city of Itatiba, Sao Paulo.
      METHODS:  We evaluated 2,054 pediatric patients (age range, 0-12 years, 11
      months) in this descriptive, transversal observational (survey) study. Data
      collection was performed by a single observer during 103 night shifts (07:00 p.m.
      to 07:00 a.m.) between January and December 2011, and included documentation of
      the main diagnosis, and patient age and sex. The ethics committee and research
      institution approved study. Patients were divided into 2 groups based on
      diagnosis: Group A otorhinolaryngology disease and Group B included diagnoses not
      contained in Group A. RESULTS:  Of the total enrolled patients, 52.2%
      corresponded to Group A and 47.8% to Group B; 51.9% were male and 48.1% were
      female. The average age was 4.5 years (Group A, 3.93 years; Group B, 5.03 years).
      We compared the prevalence of the diagnostic hypotheses of the 2 groups.
      CONCLUSION:  A large number of patients sought treatment at pediatric emergency
      rooms for otorhinolaryngologic diagnoses.

PMID- 25991988
TI  - Nasopharyngeal angiofibroma: Our experience and literature review.
AB  - INTRODUCTION:  Juvenile nasopharyngeal angiofibroma is a rare, highly vascular,
      and histologically benign tumor, generally observed in male adolescents. It shows
      very aggressive behavior due to local invasiveness and is associated with various
      symptoms. Juvenile nasopharyngeal angiofibroma originates in the sphenopalatine
      forame, causing epistaxes and nasal obstruction. OBJECTIVE:  To retrospectively
      describe our experience in the diagnosis and treatment of patients with juvenile
      nasopharyngeal angiofibroma. Scientific drawing: Retrospective, descriptive study
      conducted after approval from the Ethics Committee of the Federal University of
      Sergipe (protocol 0114.0.107.000 -11). METHODS:  We analyzed findings in 20
      patients who underwent surgery between 2004 and 2011. Factors analyzed include
      patient age and gender, symptoms, stages, treatment, length of surgery,
      intraoperatory bleeding, postoperative need for nasal tampons, hospitalization
      time, complications, and tumor recurrence. RESULTS:  Patients were aged 10-29
      years. All patients were treated surgically, including 17 who underwent
      endoscopic surgery. The mean operation time was 120 min, and the mean bleeding
      volume was 300 mL. Seventeen patients required clamping of the external carotids
      and tumor embolization. CONCLUSION:  Endoscopic surgery alone or with other
      conventional techniques was safe for the treatment of angiofibromas of different
      stages.

PMID- 25991989
TI  - Exposure to classroom sound pressure level among dance teachers in Porto Alegre
      (RS).
AB  - INTRODUCTION:  Dance teachers are exposed to high sound intensities. AIM: To
      verify the sound intensity of music used by dance teachers during classes.
      METHOD:  This was a transversal and prospective study. Dance teachers were
      evaluated with a sociodemographic questionnaire, and sound intensity level
      measurements were taken at the beginning, middle, and end of dance classes.
      RESULTS:  The sample comprised 35 teachers (average age, 31.8 years). The
      duration of their career as dance teachers was 1-37 years; they worked daily for
      approximately 1-10 h. Among the classes followed, there were 15 (42.85%)
      classical ballet classes, 4 (11.42%) tap dancing lessons, 5 (14.28%) jazz dance
      classes, 2 (5.71) Arab dance lessons, 6 (17.14%) street dance classes, and 3
      (8.57%) ballroom dancing lessons. The average values observed at the beginning,
      middle, and end of the classes were 80.91 dB (A), 83.22 dB (A), and 85.19 dB (A),
      respectively. The music played in the street dance classes exposed teachers to
      the highest sound intensity. CONCLUSION:  The average level of sound intensity of
      the dance classes in this study was either below or equal to the limit considered
      harmful for hearing health. Analysis of different class types showed that the
      sound densities of street, ballroom, and tap dance classes were above the
      recommended limits.

PMID- 25991990
TI  - Prevalence of rhinitis symptoms among textile industry workers exposed to cotton
      dust.
AB  - INTRODUCTION:  The respiratory tract is one of the main points of entry of
      foreign substances into the body. Because of its location, the respiratory tract
      is heavily exposed to harmful agents, such as gases, vapors, or aerosols. AIM: 
      Our objective was to evaluate the symptoms of occupational rhinitis in workers
      exposed to cotton dust. METHOD:  The prospective study population consisted of
      workers from the "Nova Esperanca" Cooperative of Nova Odessa (Sao Paulo), who
      were studied between September and December 2008. Data were collected through an
      individually and privately answered questionnaire designed by the author
      considering the clinical criteria for rhinitis. RESULTS:  Using the
      questionnaire, we evaluated a total of 124 workers. Among these patients, 63.7%
      complained of nasal obstruction, 57.2% of nasal itching, 46.7% of rhinorrhea, and
      66.1% of sneezing. Of the patients considered to have very serious symptoms, 9%
      had nasal obstruction; 9%, itching; 4%, rhinorrhea; and 6.4%, sneezing.
      DISCUSSION:  Aerosol agents in the environment can clearly aggravate and even
      initiate rhinitis. From the standpoint of pathogenesis, the mechanisms of
      classical allergic airway inflammation involving mast cells, IgE, histamine,
      eosinophils, and lymphocytes may be responsible for the development of rhinitis
      after exposure to high molecular weight allergens such as proteins derived from
      animals and plants. This study showed a strong relationship between the
      occupational exposures associated with work in the cotton textile industry and
      the symptoms of rhinitis. CONCLUSION:  Analysis of the data clearly showed the
      occurrence of rhinitis symptoms in these patients, demonstrating that the
      prevention and treatment of this condition in the workplace is extremely
      important.

PMID- 25991991
TI  - Cryostimulation improves recovery from oropharyngeal dysphagia after stroke.
AB  - INTRODUCTION:  Stroke is considered one of the most frequent neurological causes
      of oropharyngeal dysphagia. AIM:  To determine the effect of cryostimulation on
      oropharyngeal sensitivity and, subsequently, on the swallowing reaction and
      premature escape of food in patients with neurogenic dysphagia after stroke.
      METHODS:  Clinical and experimental study. The study enrolled 7 adult subjects, 6
      men and 1 woman ranging from 28 to 64 years of age, with a diagnosis of stroke
      and current oropharyngeal dysphagia without any other underlying disease. The
      selected subjects underwent speech-language pathology evaluation and
      videofluoroscopic assessment of the dysphagia. The subjects were then treated
      with cryostimulation consisting of 10 applications to each structure (anterior
      faucial pillar, posterior oropharyngeal wall, soft palate, and back tongue) 3
      times a day (for a total of 30 daily applications per structure) for 4
      consecutive days. The patients were then re-evaluated based on the same criteria.
      The pre- and post-cryostimulation results of the clinical and videofluoroscopic
      evaluations were analyzed descriptively and statistically using Student's t-test
      and Fisher's exact test. RESULTS:  Cryostimulation had beneficial effects on
      oropharyngeal sensitivity in 6 of the 7 subjects. There was also a significant
      improvement in swallowing and in the premature escape in six subjects.
      CONCLUSION:  Cryostimulation increased sensitivity and subsequently improved the
      swallowing reaction and premature escape of food in patients with neurogenic
      dysphagia after stroke. These effects were evident by both speech-language
      pathology and videofluoroscopic evaluation.

PMID- 25991992
TI  - Correlation analysis of the long latency auditory evoked potential N2 and
      cognitive P3 with the level of lead poisoning in children.
AB  - INTRODUCTION:  The effects of lead on children's health have been widely studied.
      AIM:  To analyze the correlation between the long latency auditory evoked
      potential N2 and cognitive P3 with the level of lead poisoning in Brazilian
      children. METHODS:  This retrospective study evaluated 20 children ranging in age
      from 7 to 14 years at the time of audiological and electrophysiological
      evaluations. We performed periodic surveys of the lead concentration in the blood
      and basic audiological evaluations. Furthermore, we studied the auditory evoked
      potential long latency N2 and cognitive P3 by analyzing the absolute latency of
      the N2 and P3 potentials and the P3 amplitude recorded at Cz. At the time of
      audiological and electrophysiological evaluations, the average concentration of
      lead in the blood was less than 10 ug/dL. RESULTS:  In conventional audiologic
      evaluations, all children had hearing thresholds below 20 dBHL for the
      frequencies tested and normal tympanometry findings; the auditory evoked
      potential long latency N2 and cognitive P3 were present in 95% of children. No
      significant correlations were found between the blood lead concentration and
      latency (p = 0.821) or amplitude (p = 0.411) of the P3 potential. However, the
      latency of the N2 potential increased with the concentration of lead in the
      blood, with a significant correlation (p = 0.030). CONCLUSION:  Among Brazilian
      children with low lead exposure, a significant correlation was found between
      blood lead levels and the average latency of the auditory evoked potential long
      latency N2; however, a significant correlation was not observed for the amplitude
      and latency of the cognitive potential P3.

PMID- 25991993
TI  - Rhinoplasty and its effects on the perception of beauty.
AB  - INTRODUCTION:  Experts on nasal cosmetics and nasal surgery agree that aesthetic
      rhinoplasty leads to overall facial beautification and the perception of youth in
      patients. This "assumed truth" has never been proven in the international
      literature. AIM:  To examine increases in facial attractiveness ratings after
      rhinoplasty surgery. METHODS:  We conducted a study series by choosing 30 female
      patients on whom we had operated and 25 evaluators in a single blind trial. The
      evaluators graded the patients' attractiveness before and after surgery. RESULTS:
      Beauty indices were significantly improved after the operation. CONCLUSION: 
      According to the third-party evaluation, the patients appeared prettier after
      undergoing aesthetic rhinoplasty.

PMID- 25991994
TI  - Degree of satisfaction among hearing aid users.
AB  - INTRODUCTION: Hearing loss (HL) is defined as the complete or partial loss of
      hearing ability. AIMS: To characterize (1) the degree of satisfaction among adult
      and elderly hearing aid (HA) users who were treated by a public hearing health
      service and (2) the relationship between satisfaction and the variables of
      gender, age, degree of HL, and type of HA. METHOD: The clinical and experimental
      study included the administration of the Satisfaction with Amplification in Daily
      Life (SADL) questionnaire to 110 patients who had used HAs for more than 3 months
      and were 18 years of age or older. RESULTS: Test patients were sex-balanced (48%
      were women) and had a mean age of 67 years. A relatively high incidence of
      sensorineural moderate HL was detected in the study patients (66%) and device B
      was the most commonly used HA type (48%). No significant differences were evident
      between HA satisfaction and sex. The importance placed on services/costs and
      personal image varied between age groups. Correlation was evident at all levels
      between user satisfaction and amplification. Decreased satisfaction was observed
      in individuals with severe and/or profound HL. The type of HA used yielded
      statistically significant differences in the positive effects referring.
      CONCLUSION: No correlations were evident between the different factors proposed.
      HA users exhibited high levels of satisfaction in all SADL areas.

PMID- 25991995
TI  - Cochlear implants and bacterial meningitis: A speech recognition study in paired
      samples.
AB  - INTRODUCTION:  Cochlear implants may guarantee sound perception and the ability
      to detect speech at a close-to-normal hearing intensity; however, differences
      have been observed among implantees in terms of performance on discrimination
      tests and speech recognition. OBJECTIVE:  To identify whether patients with post
      meningitis deafness perform similarly to patients with hearing loss due to other
      causes. METHOD:  A retrospective clinical study involving post-lingual patients
      who had been using Nucleus-22 or Nucleus-24 cochlear implants for at least 1
      year. These patients were matched with respect to age (+/- 2 years), time since
      the onset of deafness (+/- 1 year), and the duration of implant use with implant
      users who had hearing loss due to other causes. Speech perception was assessed
      using the Portuguese version of the Latin-American Protocol for the Evaluation of
      Cochlear Implants. RESULTS: The sample consisted of 52 individuals (26 in each of
      the 2 groups). The post-meningitic group had a median of 18.5 active electrodes.
      The group with hearing loss due to other causes had a median of 21, but no
      significant statistical difference was observed (p = 0.07). The results of closed
      and open-set speech recognition tests showed great variability in speech
      recognition between the studied groups. These differences were more pronounced
      for the most difficult listening tasks, such as the medial consonant task (in the
      vowel-consonant-vowel format). CONCLUSION:  Cochlear implant recipients with
      hearing loss due to bacterial meningitis, who had been using the device for 1
      year performed more poorly on closed- and open-set speech recognition tests than
      did implant recipients with hearing loss due to other causes.

PMID- 25991996
TI  - Comparison of fibrin adhesives prepared by 3 different methods.
AB  - INTRODUCTION:  Fibrin tissue adhesive, which has applications in several areas of
      medicine, can be prepared by different methods. AIM:  To compare fibrin tissue
      adhesives prepared by 3 different methods. METHOD:  In this prospective
      experimental laboratory study, fibrin tissue adhesives prepared by the use of
      plasma fibrinogen (group 1), cryoprecipitation (group 2), and precipitation by
      ammonium sulfate (group 3) were tested on 15 rabbits and 10 fragments of dura
      mater. The quality of the clots was assessed in terms of the success of the
      healing process, local toxicity, graft adhesion capacity, and degree of adhesion
      of 2 fragments of dura mater produced. RESULTS:  All methods produced a clot with
      high adhesion and no toxicity, but tensile strength testing revealed that the
      glue produced from the ammonium sulfate-precipitated clot (group 3) was the
      strongest, requiring 39 g/cm(2) to separate the fragments as opposed to 23
      g/cm(2) for group 2 and 13 g/cm(2) for group 1. CONCLUSION:  All methods produced
      good results as far as clot formation and non-toxicity, but ammonium sulfate
      precipitation produced the best tensile strength and was thus the most effective
      method of preparing fibrin tissue adhesive.

PMID- 25991997
TI  - High-speed kymography identifies the immediate effects of voiced vibration in
      healthy vocal folds.
AB  - INTRODUCTION:  The effects of voiced vibration technique can be assessed by
      laryngeal imaging. Kymographic images derived from high-speed videoendoscopy
      allow actual visualization of vocal folds vibration. PURPOSE:  The aim of this
      study is to identify the immediate effects of the voiced vibration technique in
      healthy vocal folds using high-speed digital laryngeal imaging. METHODS:  Samples
      were obtained from 15 healthy subjects with no history of voice disorders (6 men
      and 9 women aged 21 to 43 years). High-speed videoendoscopy recordings were
      performed before and after the voiced vibration technique. Kymographic images
      were obtained using high-speed videoendoscopy. The vocal folds were examined in
      their open and closed positions and the characteristics of the opening and
      closing phases were determined. A customize computational routine was used
      quantify these parameters. The closing, opening, and speed quotients were also
      calculated. RESULTS:  In this study, women displayed statistically significant
      differences in opened phase (P = 0.05*), closed phase (P = 0.046*), and closing
      phase (P = 0.026*) phase characteristics. Men displayed the highest difference
      rate in opening time characteristics (P = 0.06). The closing and opening
      quotients for the female group showed significant differences (P = 0.029* and P =
      0.049*, respectively). The speed quotient exhibited statistically significant
      differences in the male group (P = 0.048*). CONCLUSION:  The kymographic images
      indicated that the immediate effect of the voiced vibration technique was smooth
      contact in healthy vocal fold vibration.

PMID- 25991998
TI  - Firefighters' noise exposure: A literature review.
AB  - AIM:  To review the literature about the effects of environmental noise on the
      hearing ability of firefighters. METHOD:  The PubMed and Scielo databases were
      searched and studies from 2002 to 2012 that included the keywords firefighters,
      noise, and hearing loss were identified. Initially, 24 studies were selected, but
      only 10 met the inclusion criteria of investigating the effects of occupational
      noise on firefighters. RESULTS:  Only 2 (20%) studies quantified levels of sound
      pressure and performed audiological tests to identify associations with noise
      intensity and 3 (30%) questionnaire-based studies reported that these
      professionals are more susceptible to hearing loss. Four (50%) studies found that
      noise exposure damages the auditory system in this population. DISCUSSION:  These
      findings indicate that there is a necessity for preventive measures to be adopted
      by this population since it is considered to be at risk. CONCLUSION:  In recent
      years, there have been few studies of firefighters' exposure to occupational
      noise, but our findings show the importance of new studies that include proper
      means of quantifying their exposure to noise in different work environments, in
      order to identify possible adverse conditions as well as to aid in the diagnosis
      of hearing loss.

PMID- 25991999
TI  - Antibiotic prophylaxis in otolaryngologic surgery.
AB  - AIM:  Antibiotic prophylaxis aims to prevent infection of surgical sites before
      contamination or infection occurs. Prolonged antibiotic prophylaxis does not
      enhance the prevention of surgical infection and is associated with higher rates
      of antibiotic-resistant microorganisms. This review of the literature concerning
      antibiotic prophylaxis, with an emphasis on otolaryngologic surgery, aims to
      develop a guide for the use of antibiotic prophylaxis in otolaryngologic surgery
      in order to reduce the numbers of complications stemming from the indiscriminate
      use of antibiotics.

PMID- 25992000
TI  - Stethoscopes with hearing aid use: Case studies.
AB  - INTRODUCTION:  Description for using stethoscopes adapted to hearing aids. AIM: 
      To describe the adaptation of HAs to stethoscopes used by 2 students in the
      health field with bilateral hearing impairment. CASE REPORTS:  Two subjects with
      hearing loss had their stethoscopes coupled to HAs because of the individual
      requirements of their professions (healthcare) to perform auscultation.
      CONCLUSION:  The improvement was measured in situ, and satisfaction was evaluated
      using a subjective questionnaire. The use of a stethoscope coupled to an HA
      allowed students with hearing loss to perform auscultation.

PMID- 25992001
TI  - Giant cystadenoma of the floor of the mouth: A case report.
AB  - INTRODUCTION:  Cystadenoma is an uncommon epithelial neoplasia that arises from
      the salivary glands. The malignancy can affect structures such as the larynx,
      nasopharynx, buccal mucosa, and palate. OBJECTIVE:  To describe a case of a giant
      cystadenoma of the floor of the mouth treated at a public hospital in midwestern
      Brazil. CASE REPORT:  The patient was a 46-year-old woman with complaints of
      difficulties in articulating words and swallowing solid food and vocal fatigue.
      The progression of the disease since the initial consultation, the results of
      clinical examinations, and the outcome of surgery are described. Finals Comments:
      Cystadenoma must be considered in the differential diagnosis of cystic injuries
      in the floor of the mouth if the patient's symptoms are suggestive of this
      malignancy.

PMID- 25992002
TI  - Editorial.

PMID- 25992003
TI  - Phonoaudiology guidance in the preoperative period in the head and neck tumors.
AB  - INTRODUCTION:  The habit of smoking and intake of alcoholic drinks can lead to
      the incidence of malignant tumors in several areas, including the head or neck.
      Phonoaudiology is an area of oncology that is always seeking to expand its
      applications in oncological head and neck cases, with intervention in pre- and
      post-operative periods and in different clinical fields. AIM:  To evaluate and
      describe the impact of phonoaudiology preoperative guidance in patients,
      specifically smokers and alcohol drinkers, with head and neck cancer. METHODS: 
      Series Study. Interviews were conducted by telephone with 40 individuals
      diagnosed with malignant head and neck tumors. Questionnaires regarding the use
      of tobacco and alcohol were administered before and after the phonoaudiology
      preoperative guidance. RESULTS:  Among the 40 individuals who received
      phonoaudiology preoperative guidance, 26 were smokers before the orientation. Of
      these 26 individuals, 18 (69.24%) abandoned tobacco dependence, 4 (15.38%) did
      not quit smoking, and 4 (15.38%) quit smoking for a few months before resuming
      smoking after receiving phonoaudiology preoperative guidance. Regarding alcohol
      consumption, 31 individuals ingested alcohol before phonoaudiology preoperative
      guidance. Of these 31 individuals, 17 (54.84%) abandoned alcohol dependence, 8
      (25.81%) did not abstain from alcohol consumption, and 6 (19.35%) resumed alcohol
      consumption after a period of abstinence after receiving phonoaudiology
      preoperative guidance. CONCLUSION:  Phonoaudiology preoperative orientations are
      effective in the treatment of head and neck malignant tumors.

PMID- 25992004
TI  - Hearing complaints and the audiological profile of the users of an academic
      health center in the western region of Sao Paulo.
AB  - INTRODUCTION:  Few population-based studies have quantified hearing levels in
      Brazil; additional studies on this subject are needed. PURPOSE:  The purpose of
      this study was to characterize hearing complaints and the audiological profile of
      the population served by the Clinical Audiology Service of an Academic Health
      Center in the western region of Sao Paulo, Brazil, between 2003 and 2008. An
      additional aim was to check whether there is a positive association between the
      signs/symptoms and type of hearing loss. METHODS:  This was a retrospective study
      of the records of 2,145 patients. The health history, tonal and vocal audiometry,
      and imitanciometry findings were analyzed. RESULTS:  The mean age of the patients
      was 20.6 years. The majority of the subjects had normal hearing thresholds, and
      the prevalence of hearing loss was approximately 35%. As the patient's age
      increased, the frequency of conductive hearing loss decreased and that of
      sensorineural hearing loss increased. There was a tendency toward hearing loss
      worsening with age. CONCLUSION:  Hearing complaints can predict the type of
      hearing loss; therefore, they should always be valued because they can be used as
      a form of screening and thus help to determine the diagnostic hypothesis. This
      could help to reduce the gap between the patient's perception of the complaints
      and the audiological assessment and thus improve the prognosis.

PMID- 25992005
TI  - Olfactory neuroepithelium in the superior and middle turbinates: which is the
      optimal biopsy site?
AB  - INTRODUCTION:  Olfactory neuroepithelium (ON) biopsy has several therapeutic
      applications for both disorders of olfaction and neurodegenerative diseases.
      Successful collection of ON is still anything but routine due to a dearth of
      studies on the distribution of ON in the superior and middle turbinates. AIM:  To
      determine the location in which ON is most likely to be present in endoscopically
      removed cadaver superior and middle turbinates as well as the influences of
      gender, age, and naris side on the presence of ON and the extent to which it is
      present. METHODS:  We conducted a prospective anatomical study. The superior and
      middle turbinates on both sides endoscopically removed from 25 fresh cadavers
      (less than 12 h post-mortem). The turbinates were halved into anterior and
      posterior segments for a total of 200 specimens, which were analyzed after
      hematoxylin and eosin and immunohistochemical staining. Hematoxylin and eosin
      stained slides were subjected to blind examination by 3 independent pathologists,
      and the presence of ON was graded on a 5-point scale from 0 to 4. Kappa
      measurement was used to determine the agreement between pairs of observers.
      RESULTS:  ON was present in 82.9% of superior turbinate samples and in 17.1% of
      middle turbinate samples. Immunohistochemistry detected ON in superior turbinates
      only by S-100 staining and only in 15 fragments. Gender, age, and naris side had
      no statistically significant effects on the presence of ON. CONCLUSION:  When
      biopsying ON, the posterior portion of the superior turbinate should be targeted
      whenever possible because it has the highest concentration of ON among the nasal
      structures.

PMID- 25992006
TI  - Vestibular evoked myogenic potentials and digital vectoelectro-nystagmography's
      study in patients with benign paroxysmal positional vertigo.
AB  - INTRODUCTION:  Benign Paroxysmal Positional Vertigo (BPPV) is a very common
      vestibular disorder characterized by brief but intense attacks of rotatory
      vertigo triggered by simple rapid movement of the head. The integrity of the
      vestibular pathways can be assessed using tests such as digital
      vectoelectronystagmography (VENG) and vestibular evoked myogenic potentials
      (VEMP). AIM:  This study aimed to determine the VEMP findings with respect to
      latency, amplitude, and waveform peak to peak and the results of the oculomotor
      and vestibular components of VENG in patients with BPPV. METHOD:  Although this
      otoneurological condition is quite common, little is known of the associated VEMP
      and VENG changes, making it important to research and describe these results.
      RESULTS:  We examined the records of 4438 patients and selected 35 charts after
      applying the inclusion and exclusion criteria. Of these, 26 patients were women
      and 9 men. The average age at diagnosis was 52.7 years, and the most prevalent
      physiological cause, accounting for 97.3% of cases, was ductolithiasis. There was
      a statistically significant association between normal hearing and mild
      contralateral sensorineural hearing loss. The results of the oculomotor tests
      were within the normal reference ranges for all subjects. Patients with BPPV
      exhibited symmetrical function of the semicircular canals in their synergistic
      pairs (p < 0.001). The caloric test showed statistically normal responses from
      the lateral canals. The waveforms of all patients were adequate, but the VEMP
      results for the data-crossing maneuver with positive positioning showed a trend
      toward a relationship for the left ear Lp13. There was also a trend towards an
      association between normal reflexes in the caloric test and the inter-peak VEMP
      of the left ear. It can be concluded that although there are some differences
      between the average levels of the VENG and VEMP results, these differences were
      not statistically significant. CONCLUSION:  In conclusion, the results of
      audiologic assessment, hearing thresholds, positioning maneuvers, and caloric
      tests have no effect on the quantitative results of VEMP. Additional research is
      warranted to establish the relationships among VENG, VEMP, and BPPV, especially
      as concerns the oculomotor tests.

PMID- 25992007
TI  - Association between complaints of dizziness and hypertension in non
      institutionalized elders.
AB  - INTRODUCTION:  Advancing age increases the risk for a number of chronic diseases.
      Hypertension and dizziness are highly prevalent in the elderly population and
      represent major health problems. OBJECTIVE:  To verify the association between
      complaints of dizziness and the presence of hypertension in non-institutionalized
      elders. METHOD:  This was a prospective cross-sectional cohort study of the
      elderly population of Londrina, Parana in terms of aging and longevity. The
      required sample size was calculated, and subjects e" 60 years of age of both
      genders were selected at random. Data were collected using a questionnaire
      covering socio-demographic information and self-reported cases of hypertension
      and dizziness. Statistical analysis was performed using the chi-square test with
      p d" 0.05 as the level of significance. RESULTS:  The study included 493 elderly
      subjects, of whom 257 (52.1%) complained of dizziness and 308 (62.5%) reported a
      diagnosis of arterial systemic hypertension. Dizziness was significantly
      associated with hypertension (chi2 = 6.26, p = 0.01) and female sex. CONCLUSIONS:
      Hypertension and dizziness were both highly prevalent and were significantly
      associated, showing the great need for investments in preventive measures.

PMID- 25992008
TI  - Effect of fractionated radiotherapy on the parotid gland: an experimental study
      in Brazilian minipigs.
AB  - INTRODUCTION:  Radiotherapy (RT) of head and neck neoplasms often damages the
      salivary glands. AIM:  To examine the pattern of morphologic changes resulting
      from RT of the head and neck region in minipig parotid glands in a clinical and
      experimental research setting. METHODS:  Twelve 18-month-old male Brazilian
      minipigs weighing 30-40 kg were selected. Eight minipigs were assigned to the
      experimental group (group 1) and 4 to the control group (group 2). The RT was
      performed under general anesthesia at Erasto Gaertner Hospital, Curitiba, Brazil,
      using an a/a ratio of 2.5. The minipigs from group 1 underwent 3 sessions of
      irradiation with Cobalt 60 of the head and neck, bilaterally, with 3 exposures of
      8 Gy each at 7-day intervals for a total dose of 24 Gy. The animals were
      sacrificed 12 weeks post-RT. RESULTS:  The irradiated parotid glands displayed
      reductions in the size and number of acini as well as loss of secretory granules.
      The presence of fibrosis and loss of parenchyma relative to non-irradiated glands
      were observed, with an average reduction in volume of 54%. CONCLUSIONS:  Our
      results demonstrate that this model for parotid gland damage resulting from an RT
      regimen appears to be useful for preclinical large animal studies of RT-induced
      damage and testing novel potential treatment options. Although recent advances in
      radiation therapy, such as intensity-modulated radiation therapy, have reduced
      the dose and limited the field of radiation, considerable salivary gland injury
      still occurs and can greatly impact the patient's quality of life after cancer
      treatment.

PMID- 25992009
TI  - A brief history of mastoidectomy.
AB  - AIM:  To describe to the new generation of otologists the origins of
      mastoidectomy as well as the difficulties our predecessors encountered and the
      solutions they devised to improve otologic surgery. METHOD:  Retrospective
      literature review-based study. RESULTS:  Before the mid-19th century,
      mastoidectomy was performed only sporadically and in most cases as a desperate
      attempt to save the lives of people suffering from complications of infectious
      otitis. The drainage of acute abscesses became a common procedure at the
      beginning of the 20th century, within the pre-antibiotic era. The first
      documented surgical incision to drain an infected ear was described by the French
      physician Ambroise Pare in the 16th century. The credit for performing the first
      mastoidectomy for the removal of purulent secretions went to Jean-Louis Petit.
      Mastoidectomies were normally performed to treat infections. However,
      mastoidectomies were also carried out for other purposes, particularly for the
      treatment of deafness and tinnitus, during various periods. Sir Charles Ballance
      credited Johannes Riolanus with recommending mastoidectomy for the treatment of
      tinnitus. William Wilde began the era of modern mastoidectomy with his
      introduction of the eponymous retroauricular incision. CONCLUSION:  Mastoidectomy
      has evolved significantly throughout its history. Improvements in mastoidectomy
      have relied on the introduction of more elaborate surgical procedures, especially
      the advances in surgical equipment during the last century. Mastoidectomy
      continues to be a life-saving surgical procedure.

PMID- 25992010
TI  - Hearing loss in the elderly: History of occupational noise exposure.
AB  - INTRODUCTION:  Noise exposure is one of the most common health risk factors, and
      workers are exposed to sound pressure levels capable of producing hearing loss.
      AIM:  To assess the prevalence of hearing loss in the elderly and its possible
      association with a history of occupational noise exposure and with sex. METHODS: 
      A prospective study in subjects aged over 60 years. The subjects underwent
      anamnesis and audiological assessment. The Mann-Whitney test and multiple
      logistic regression, with 95% confidence interval and p < 0.05, were used for
      statistical analysis. RESULTS:  There were 498 subjects from both sexes, and the
      median age was 69 years. From the comparison between men and women, we obtained
      the medium hearing I (500, 1000, and 2000 Hz p = 0.8318) and the mean hearing II
      (3000, 4000, and 6000 Hz; p < 0.0001). Comparing the thresholds of individuals
      with and without a history of occupational noise exposure, we obtained the medium
      hearing I (p = 0.9542) and the mean hearing II (p = 0.0007). CONCLUSION:  There
      was a statistically significant association between hearing loss at high
      frequencies and the risk factors being male and occupational noise exposure.

PMID- 25992011
TI  - Auditory complaints and audiologic assessment in children with surgically
      repaired cleft lip and palate.
AB  - INTRODUCTION:  At the initial consultation, the speech-language pathologist and
      audiologist may consider possible diagnostic hypotheses based on the child's
      history and the parents' complaint. AIM:  To investigate the association of
      hearing complaints with the findings obtained in the conventional audiologic
      assessment in children with cleft lip and palate. Retrospective study. METHODS: 
      We analyzed medical charts of 1000 patients with cleft lip and palate who
      underwent surgical repair between 1988 and 1995 at a mean age of 6 years 8
      months. We excluded charts with records of inconsistent audiological responses
      and charts with missing data for any of the audiologic evaluations considered.
      Thus, the sample consisted of 393 records. RESULTS:  Two hundred thirty-nine
      patients presented hearing loss in one or both ears, but only 3.8% reported
      hearing complaints. The most frequent were otorrhea followed by otalgia. There
      was no statistical significance between the complaint and gender (p = 0.26) nor
      between the complaint and hearing loss (p = 0.83). CONCLUSION:  This study showed
      no association between the hearing complaint and the conventional audiologic
      assessment.

PMID- 25992012
TI  - Advances in the treatment of children with phonological disorders.
AB  - INTRODUCTION:  Treatment of phonological disorders considering extra-linguistic
      and linguistic variables are important to ensure that the alteration is resolved
      promptly and in the best manner as possible. AIM:  To analyze therapeutic
      advances (phonetic inventory, phonological system, and distinctive features) in
      children with phonological disorders by considering the therapeutic approach
      used, the severity of the phonological disorder, age, and the number of
      therapeutic sessions. METHODS:  We conducted a case series study of 94 children
      aged 3 years, 9 months through 8 years, 5 months. The children were divided into
      groups based on the therapeutic approach used (Modified Cycles, Maximal
      Oppositions, ABAB-Withdrawal, and Multiple Probes), the severity of their
      phonological disorder, age, and the number of therapy sessions with each
      individual. Phonetic inventory, the phonological system, and the number of
      altered distinctive features were analyzed. RESULTS:  The greater the number of
      therapy sessions, the greater the number of sounds acquired. The number of sounds
      present in the phonetic inventory and phonological system increased and the
      severity of the phonological disorder decreased with all of the therapeutic
      approaches studied. There was also a reduction in the incidence of altered
      distinctive features. CONCLUSION:  There was a favorable evolution in phonetic
      inventory and phonological system acquisitions as well as a reduction in the
      number of altered distinctive features for all 3 therapeutic models regardless of
      the severity of the phonological disorder, age, or number of sessions.

PMID- 25992013
TI  - Sound pressure level in a municipal preschool.
AB  - AIM:  To evaluate the sound pressure level to which preschool students are
      exposed. METHOD:  This was a prospective, quantitative, nonexperimental, and
      descriptive study. To achieve the aim of the study we used an audio dosimeter.
      The sound pressure level (SPL) measurements were obtained for 2 age based
      classrooms. Preschool I and II. The measurements were obtained over 4 days in 8
      hour sessions, totaling 1920 minutes. RESULTS:  Compared with established
      standards, the SPL measured ranged from 40.6 dB (A) to 105.8 dB (A). The
      frequency spectrum of the SPL was concentrated in the frequency range between 500
      Hz and 4000 Hz. The older children produced higher SPLs than the younger ones,
      and the levels varied according to the activity performed. Painting and writing
      were the quietest activities, while free activities period and games were the
      noisiest. CONCLUSION:  The SPLs measured at the preschool were higher and
      exceeded the maximum permitted level according to the reference standards.
      Therefore, the implementation of actions that aim to minimize the negative impact
      of noise in this environment is essential.

PMID- 25992015
TI  - Noise-Induced Hearing Loss (NIHL): literature review with a focus on occupational
      medicine.
AB  - According to the Ministry of Health (2006), Noise-Induced Hearing Loss (NIHL) is
      hearing loss caused by prolonged exposure to noise. It is characterized as
      sensorineural hearing loss and is usually bilateral, irreversible, and
      progressive while the exposure to noise continues. A NIHL is a predictable and
      preventable disease with an epidemiologically relevant prevalence in urban
      communities. The hearing loss begins and predominates in the frequencies of 3, 4,
      and 6 kHz and eventually progresses to 8, 2, 1, 0.5, and 0.25 kHz. In Brazil,
      regulatory standard 15 limits the exposure to continuous noise to no more than 4
      hours' exposure to 90 dBA and a maximum level of 85 dB for a full 8-hour working
      period. As NIHL is a preventable and predictable disease, preventive action by
      professionals may be able to change the prevalence of hearing loss in noisy
      environments. 

PMID- 25992014
TI  - The relationship between the speech perception and the degree of satisfaction
      among adult users of cochlear implants.
AB  - INTRODUCTION:  In recent years, the benefits associated with the use of cochlear
      implants (CIs), especially with regard to speech perception, have proven to
      surpass those produced by the use of hearing aids, making CIs a highly efficient
      resource for patients with severe/profound hearing loss. However, few studies so
      far have assessed the satisfaction of adult users of CIs. OBJECTIVE:  To analyze
      the relationship between the level of speech perception and degree of
      satisfaction of adult users of CI. METHOD:  This was a prospective cross
      sectional study conducted in the Audiological Research Center (CPA) of the
      Hospital of Craniofacial Anomalies, University of Sao Paulo (HRAC/USP), in Bauru,
      Sao Paulo, Brazil. A total of 12 users of CIs with pre-lingual or post-lingual
      hearing loss participated in this study. The following tools were used in the
      assessment: a questionnaire, "Satisfaction with Amplification in Daily Life"
      (SADL), culturally adapted to Brazilian Portuguese, as well as its relationship
      with the speech perception results; a speech perception test under quiet
      conditions; and the Hearing in Noise Test (HINT)Brazil under free field
      conditions. RESULTS:  The participants in the study were on the whole satisfied
      with their devices, and the degree of satisfaction correlated positively with the
      ability to perceive monosyllabic words under quiet conditions. The satisfaction
      did not correlate with the level of speech perception in noisy environments.
      CONCLUSION:  Assessments of satisfaction may help professionals to predict what
      other factors, in addition to speech perception, may contribute to the
      satisfaction of CI users in order to reorganize the intervention process to
      improve the users' quality of life.

PMID- 25992016
TI  - Extramedullary nasal plasmacytoma: Literature review and a rare case report.
AB  - INTRODUCTION:  Extramedullary plasmacytoma is a plasma cell tumor that grows
      within any of the soft tissues of the organism. Similar to all plasmacytic
      dyscrasia, the disease is extremely rare. AIM:  This study reports a case of an
      extramedullary plasmacytoma of the nasal cavity and provides a literature review
      on the topic. CASE REPORT:  A 51-year-old woman presented at our tertiary
      university hospital with a 6-month history of progressive nasal obstruction,
      predominantly to the right side, and self-limiting epistaxis. Examination
      revealed a large pale-reddish tumor within the right nasal cavity.
      Anatomopathological analysis showed features consistent with a plasmacytoma
      diagnosis, which was subsequently confirmed by immunohistochemical techniques.
      Further assessment revealed the solitary nature of the condition, consistent with
      extramedullary plasmacytoma. Radiotherapy was initiated, which led to partial
      regression of the symptoms. The tumor was surgically removed by using a mid
      facial degloving approach. The patient evolved with a naso-oral fistula and
      underwent 3 corrective surgeries. No evidence of associated systemic disease was
      found after 5 years of follow-up. CONCLUSIONS:  This case report, which describes
      a rare tumor of the nasal cavity, is expected to improve the recognition and
      referral of this condition by ear, nose, and throat (ENT) specialists for
      multidisciplinary management and long-term follow-up.

PMID- 25992017
TI  - Chondro-osseous respiratory epithelial adenomatoid hamartoma of the nasal cavity.
AB  - INTRODUCTION:  Chondro-osseous respiratory epithelial adenomatoid hamartoma
      (COREAH) is a benign lesion of the nose and sinuses that is extremely rare, with
      only 2 cases reported in the literature to date. CASE REPORT:  We present herein
      the third reported case of COREAH, in a 38-year-old woman who presented with left
      nasal obstruction and a mass in her left nasal cavity. The mass was completely
      resected endoscopically. Microscopic examination showed hamartomatous
      proliferation of respiratory-type glands with mucinous metaplasia admixed with
      numerous spicules of mature bone, characteristic of COREAH. CONCLUSION:  COREAH
      is a benign hamartomatous proliferation of respiratory epithelium, submucosal
      glands, and chondro-osseous mesenchyme. The clinical differential diagnoses for
      such lesions include glandular hamartoma, inflammatory polyp, inverted papilloma,
      and low-grade sinonasal adenocarcinoma. Recognition of this lesion as benign
      despite its potentially worrisome radiographic appearance is important to avoid
      an unnecessarily radical surgical procedure.

PMID- 25992019
TI  - International archives of otorhinolaryngology and thieme medical publishers.

PMID- 25992018
TI  - Results of the implantation of bone-anchored hearing aids in patients with
      treacher-collins syndrome.
AB  - INTRODUCTION:  Treacher-Collins syndrome is characterized by craniofacial
      malformations, narrowing of the external auditory canal (EAC), and, in 30% of
      cases, agenesis of the canal and ossicular chain defects. The use of hearing aids
      (HA) is not possible in cases in which agenesis or stenosis of the EAC
      accompanies conductive deafness. In contrast, bone conduction implants such as
      the Bone Anchored Hearing Aid (BAHA((r))) allow direct stimulation of the cochlea
      and are thus superior to conventional hearing aids in cases of severe conductive
      hearing loss. OBJECTIVE:  To present 2 cases of patients with Treacher-Collins
      syndrome who underwent implantation of BAHA((r)). CASES REPORTS:  The first
      patient was a 52-year-old woman diagnosed with Treacher-Collins syndrome who
      presented with severe bilateral mixed hearing loss and a history of unsuccessful
      previous use of a bone contact conduction device. The BAHA((r)) implantation was
      uneventful, and the post-operative results were good. The second patient was a 14
      year-old girl who was also diagnosed with Treacher-Collins Syndrome with
      bilateral moderate conductive hearing loss by audiometry. The use of a bone
      vibrator contact device did not improve her hearing; however, implantation of a
      BAHA((r)) resulted in a decreased gap postoperatively. Final comments: BAHA((r))
      hearing devices provide adequate rehabilitation and consequent improvement of the
      quality of life in patients with Treacher-Collins syndrome.

PMID- 25992020
TI  - Tympanomastoidectomy: Comparison between canal wall-down and canal wall-up
      techniques in surgery for chronic otitis media.
AB  - INTRODUCTION:  Chronic otitis media (COM) is an inflammatory condition associated
      with otorrhea as well as large and persistent perforations of the tympanic
      membrane in some cases. COM can also lead to cholesteatoma. Surgical treatment
      with canal wall-down and canal wall-up tympanomastoidectomy is considered for
      both types of illness. The choice of technique is controversial and is dependent
      on several factors, including the extent of disease. OBJECTIVE:  We aimed to
      evaluate surgical outcomes in COM patients with and without cholesteatoma treated
      with canal wall-down and canal wall-up tympanomastoidectomy. Disease eradication
      and post-operative auditory thresholds were assessed. METHOD:  Patient records
      from the otorhinolaryngology department of a tertiary hospital were assessed
      retrospectively. RESULTS:  Patients who underwent canal wall-up
      tympanomastoidectomy had a higher rate of revision surgery, especially those with
      cholesteatoma. However, there were no statistically significant differences in
      post-operative hearing thresholds between the two techniques. CONCLUSION:  The
      canal wall-down technique is superior to the canal wall-up technique, especially
      for patients with cholesteatoma.

PMID- 25992021
TI  - Endoscopic surgery in the treatment of crista galli pneumatization evolving with
      localizated frontal headaches.
AB  - INTRODUCTION:  The crista galli is part of the ethmoid bone and thus may suffer
      from the process of pneumatization. Pneumatization occurs in between 3% and 14%
      of patients, resulting from air cells in the frontal or ethmoid sinuses. AIM:  To
      describe 3 cases of crista galli pneumatization in which the patients developed
      infection and were treated surgically by endoscopic techniques. METHOD:  We
      present 3 case studies of patients complaining of severe frontal headaches. The
      patients underwent ENT evaluation, examination by video-endoscopy, and computed
      tomography, which identified crista galli pneumatization with mucosal thickening
      and the presence of fluid. Patients underwent treatment with antibiotics and
      corticosteroids; however, they showed no symptomatic improvement, displayed
      recurrence of symptoms, and maintained radiographic changes. Thus, patients then
      underwent drainage through the crista galli via an endoscopic procedure.
      DISCUSSION:  During surgery, mucopurulence and/or mucosal thickening and edema
      were identified in the pneumatized crista galli. There were no complications
      during or after surgery. Postoperatively, headache was improved in patients after
      a minimum follow-up of 6 months. CONCLUSION:  Crista galli pneumatization can
      result in infection, simulating rhinosinusitis. When there is little response to
      drug therapy, endoscopic surgical treatment is required; the current cases
      demonstrate that this technique is safe and effective.

PMID- 25992022
TI  - Velopharyngeal dysfunction: a systematic review of major instrumental and
      auditory-perceptual assessments.
AB  - INTRODUCTION:  Velopharyngeal dysfunction may cause impaired verbal communication
      skills in individuals with cleft lip and palate; thus, patients with this
      disorder need to undergo both instrumental and auditory-perceptual assessments.
      OBJECTIVE:  To investigate the main methods used to evaluate velopharyngeal
      function in individuals with cleft lip and palate and to determine whether there
      is an association between videonasoendoscopy results and auditory-perceptual
      assessments. METHOD:  We conducted a systematic review of the literature on
      instrumental and auditory-perceptual assessments. We searched the PubMed,
      Medline, Lilacs, Cochrane, and SciELO databases from October to November 2012.
      SUMMARY OF FINDINGS:  We found 1,300 studies about the topic of interest
      published between 1990 and 2012. Of these, 56 studies focused on velopharyngeal
      physiology; 29 studies presented data on velopharyngeal physiology using at least
      1 instrumental assessment and/or 1 auditory-perceptual assessment, and 12 studies
      associated the results of both types of assessments. Only 3 studies described in
      detail the analysis of both methods of evaluating velopharyngeal function;
      however, associations between these findings were not analyzed. CONCLUSION:  We
      found few studies clearly addressing the criteria chosen to investigate
      velopharyngeal dysfunction and associations between videonasoendoscopy results
      and auditory-perceptual assessments.

PMID- 25992023
TI  - Comparison of videonasoendoscopy and auditory-perceptual evaluation of speech in
      individuals with cleft lip/palate.
AB  - INTRODUCTION:  The velopharyngeal sphincter (VPS) is a muscle belt located
      between the oropharynx and the nasopharynx. Investigations of velopharyngeal
      function should include an auditory-perceptual evaluation and at least 1
      instrument-based evaluation such as videonasoendoscopy. AIM:  To compare the
      findings of auditory-perceptual evaluation (hypernasality) and videonasoendoscopy
      (gap size) in individuals with cleft lip/palate. METHOD:  This was a
      retrospective, cross-sectional study assessing 49 subjects, of both sexes, with
      cleft lip/palate followed up at the Otorhinolaryngology Service and the Speech
      Therapy outpatient clinic of Hospital de Clinicas de Porto Alegre (HCPA). The
      results from the auditory-perceptual evaluation and the videonasoendoscopy test
      were compared with respect to the VPS gap size. RESULTS:  Subjects with
      moderate/severe hypernasality had more severe velopharyngeal closure impairment
      than those with a less severe condition. The interaction between hypernasality
      severity and the presence of other speech disorders (p = 0.035), whether
      compensatory and/or obligatory, increased the likelihood of having a moderate-to
      large gap in the velopharyngeal closure. CONCLUSIONS:  We observed an association
      between the findings of these 2 evaluation methods.

PMID- 25992024
TI  - Characteristics of polypoid lesions in patients undergoing microsurgery of the
      larynx.
AB  - INTRODUCTION:  Dysphonia is the main symptom of lesions that affect the vocal
      tract. Many of those lesions may require surgical treatment. Polyps are one of
      the most common forms of vocal cord lesions and the most prevalent indication for
      laryngeal microsurgery. There are different types of polyps, and their different
      characteristics can indicate different prognosis and treatments. AIM:  To conduct
      a comparative study of polypoid lesions (angiomatous and gelatinous) in patients
      undergoing laryngeal microsurgery via an electronic protocol. METHOD:  We
      prospectively evaluated 93 patients diagnosed with vocal fold polyps; the polyps
      were classified as angiomatous or gelatinous. RESULTS:  In total, 93 patients
      undergoing laryngeal microsurgery were diagnosed with vocal fold polyps. Of
      these, 63 (64.74%) had angiomatous and 30 (32.26%) gelatinous polyps. Most
      patients with angiomatous polyps were men; their polyps were frequently of medium
      size, positioned in the middle third of the vocal fold, and accompanied by
      minimal structural alterations (MSA). In contrast, the majority of patients with
      gelatinous polyps were women; their polyps were smaller, positioned in the middle
      and posterior third of the vocal fold, and were not accompanied by MSA. Both
      types of polyps were more frequently located on the right vocal fold. CONCLUSION:
      Angiomatous polyps were more frequently encountered than gelatinous polyps. In
      addition, correlations between polyp type and sex, polyp size, position,
      location, and the presence of MSA were observed. Different surgical techniques
      were used, but the postoperative results were similar and satisfactory after
      speech therapy.

PMID- 25992025
TI  - Audiological outcomes of cochlear implantation in Waardenburg Syndrome.
AB  - INTRODUCTION:  The most relevant clinical symptom in Waardenburg syndrome is
      profound bilateral sensorioneural hearing loss. AIM:  To characterize and
      describe hearing outcomes after cochlear implantation in patients with
      Waardenburg syndrome to improve preoperative expectations. METHOD:  This was an
      observational and retrospective study of a series of cases. Children who were
      diagnosed with Waardenburg syndrome and who received a multichannel cochlear
      implant between March 1999 and July 2012 were included in the study.
      Intraoperative neural response telemetry, hearing evaluation, speech perception,
      and speech production data before and after surgery were assessed. RESULTS: 
      During this period, 806 patients received a cochlear implant and 10 of these
      (1.2%) were diagnosed with Waardenburg syndrome. Eight of the children received a
      Nucleus 24((r)) implant and 1 child and 1 adult received a DigiSonic SP implant.
      The mean age at implantation was 44 months among the children. The average
      duration of use of a cochlear implant at the time of the study was 43 months.
      Intraoperative neural responses were present in all cases. Patients who could use
      the speech processor effectively had a pure tone average of 31 dB in free-field
      conditions. In addition, the MUSS and MAIS questionnaires revealed improvements
      in speech perception and production. Four patients did not have a good outcome,
      which might have been associated with ineffective use of the speech processor.
      CONCLUSION:  Despite the heterogeneity of the group, patients with Waardenburg
      syndrome who received cochlear implants were found to have hearing thresholds
      that allowed access to speech sounds. However, patients who received early
      intervention and rehabilitation showed better evolution of auditory perception.

PMID- 25992026
TI  - Performance analysis of ten brands of batteries for hearing aids.
AB  - INTRODUCTION:  Comparison of the performance of hearing instrument batteries from
      various manufacturers can enable otologists, audiologists, or final consumers to
      select the best products, maximizing the use of these materials. AIM:  To analyze
      the performance of ten brands of batteries for hearing aids available in the
      Brazilian marketplace. METHODS:  Hearing aid batteries in four sizes were
      acquired from ten manufacturers and subjected to the same test conditions in an
      acoustic laboratory. RESULTS:  The results obtained in the laboratory contrasted
      with the values reported by manufacturers highlighted significant discrepancies,
      besides the fact that certain brands in certain sizes perform better on some
      tests, but does not indicate which brand is the best in all sizes. CONCLUSIONS: 
      It was possible to investigate the performance of ten brands of hearing aid
      batteries and describe the procedures to be followed for leakage, accidental
      intake, and disposal.

PMID- 25992027
TI  - Contribution of audiovestibular tests to the topographic diagnosis of sudden
      deafness.
AB  - INTRODUCTION:  Sudden hearing loss (SHL) is an ENT emergency defined as
      sensorineural hearing loss (SNHL) >= 30 dB HL affecting at least 3 consecutive
      tonal frequencies, showing a sudden onset, and occurring within 3 days. In cases
      of SHL, a detailed investigation should be performed in order to determine the
      etiology and provide the best treatment. Otoacoustic emission (OAE) analysis,
      electronystagmography (ENG), bithermal caloric test (BCT), and vestibular evoked
      myogenic potential (VEMP) assessments may be used in addition to a number of
      auxiliary methods to determine the topographic diagnosis. Objective To evaluate
      the contribution of OAE analysis, BCT, VEMP assessment, and magnetic resonance
      imaging (MRI) to the topographic diagnosis of SHL. Method Cross-sectional and
      retrospective studies of 21 patients with SHL, as defined above, were performed.
      The patients underwent the following exams: audiometry, tympanometry, OAE
      analysis, BCT, VEMP assessment, and MRI. Sex, affected side, degree of hearing
      loss, and cochleovestibular test results were described and correlated with MRI
      findings. Student's t-test was used for analysis of qualitative variables (p <
      0.05). Results The mean age of the 21 patients assessed was 52.5 +/- 15.3 years;
      13 (61.9%) were women and 8 (38.1%) were men. Most (55%) had severe hearing loss.
      MRI changes were found in 20% of the cases. When the audiovestibular test results
      were added to the MRI findings, the topographic SHL diagnosis rate increased from
      20% to 45%. Conclusion Only combined analysis via several examinations provides a
      precise topographic diagnosis. Isolated data do not provide sufficient evidence
      to establish the extent of involvement and, hence, a possible etiology.

PMID- 25992028
TI  - Diffusion of aniline blue injected into the thyroarytenoid muscle as a proxy for
      botulinum toxin injection: an experimental study in cadaver larynges.
AB  - INTRODUCTION:  Endolaryngeal injection of botulinum toxin into the thyroarytenoid
      (TA) muscle is one of the methods for treatment of focal laryngeal dystonia.
      However, after treatment, there is variation in laryngeal configuration as well
      as the side effects reported by patients. As a consequence of the functional
      variability of results, it was hypothesized that botulinum toxin diffuses beyond
      the limits of the muscle into which it is injected. OBJECTIVES:  After injection
      of botulinum toxin into the TA muscle for the treatment of focal laryngeal
      dystonia, patients differ in terms of laryngeal configuration and side effects.
      We hypothesized that this toxin diffuses from the target muscle to adjacent
      muscles. METHOD:  The TA muscles of 18 cadaver larynges were injected with
      aniline blue (0.2 mL). After fixation in formaldehyde and nitric acid
      decalcification, the larynges were sectioned in the coronal plane and the
      intrinsic muscles were analyzed. RESULTS:  We found diffusion of aniline blue to
      the lateral cricoarytenoid muscle, cricothyroid muscle, and posterior
      cricoarytenoid muscle in 94.3%, 42.9%, and 8.6% of the cases, respectively. In
      terms of the degree of diffusion to adjacent muscles, we found no differences
      related to the size (height and width) of the TA muscle or to gender.
      CONCLUSIONS:  Our findings suggest that diffusion of botulinum toxin from its
      injection site in the TA muscle to the lateral cricoarytenoid muscle is likely in
      most cases. On the other hand, diffusion to the cricothyroid muscle occurs in
      approximately half of cases and diffusion to the posterior cricoarytenoid muscle
      occurs in very few cases.

PMID- 25992029
TI  - Correlation of cephalometric and anthropometric measures with obstructive sleep
      apnea severity.
AB  - INTRODUCTION:  Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)
      often have associated changes in craniofacial morphology and distribution of body
      fat, either alone or in combination. AIM:  To correlate cephalometric and
      anthropometric measures with OSAHS severity by using the apnea-hypopnea index
      (AHI). METHOD:  A retrospective cephalometry study of 93 patients with OSAHS was
      conducted from July 2010 to July 2012. The following measurements were evaluated:
      body mass index (BMI), neck circumference (NC), waist circumference (WC), hip
      circumference (HC), the angles formed by the cranial base and the maxilla (SNA)
      and the mandible (SNB), the difference between SNA and SNB (ANB), the distance
      from the mandibular plane to the hyoid bone (MP-H), the space between the base of
      the tongue and the posterior pharyngeal wall (PAS), and the distance between the
      posterior nasal spine and the tip of the uvula (PNS-P). Means, standard
      deviations, and Pearson's correlation coefficients were calculated and analyzed.
      RESULTS:  AHI correlated significantly with BMI (r = 0.207, p = 0.047), NC (r =
      0.365, p = 0.000), WC (r = 0.337, p = 0.001), PNS-P (r = 0.282, p = 0.006), and
      MP-H (r = 0.235, p = 0.023). CONCLUSION:  Anthropometric measurements (BMI, NC,
      and WC) and cephalometric measurements (MP-H and PNS-P) can be used as predictors
      of OSAHS severity.

PMID- 25992030
TI  - Use of surface electromyography in phonation studies: an integrative review.
AB  - INTRODUCTION: Surface electromyography has been used to assess the extrinsic
      laryngeal muscles during chewing and swallowing, but there have been few studies
      assessing these muscles during phonation. OBJECTIVE:  To investigate the current
      state of knowledge regarding the use of surface electromyography for evaluation
      of the electrical activity of the extrinsic muscles of the larynx during
      phonation by means of an integrative review. METHOD:  We searched for articles
      and other papers in the PubMed, Medline/Bireme, and Scielo databases that were
      published between 1980 and 2012, by using the following descriptors: surface
      electromyography and voice, surface electromyography and phonation, and surface
      electromyography and dysphonia. The articles were selectedon the basis
      ofinclusion and exclusion criteria. DATA SYNTHESIS:  This was carried out with a
      cross critical matrix. We selected 27 papers,i.e., 24 articles and 3 theses. The
      studies differed methodologically with regards to sample size and investigation
      techniques, making it difficult to compare them, but showed differences in
      electrical activity between the studied groups (dysphonicsubjects, non
      dysphonicsubjects, singers, and others). CONCLUSION:  Electromyography has
      clinical applicability when technical precautions with respect to application and
      analysis are obeyed. However, it is necessary to adopt a universal system of
      assessment tasks and related measurement techniques to allow comparisons between
      studies.

PMID- 25992031
TI  - Middle ear adenoma with neuroendocrine differentiation: relate of two cases and
      literature review.
AB  - INTRODUCTION:  Adenomas with neuroendocrine differentiation are defined as
      neuroendocrine neoplasms, and they are rarely found in the head and neck.
      OBJECTIVE:  To describe two cases of a middle ear adenoma with neuroendocrine
      differentiation, with a literature review. CASE REPORT:  Patient 1 was a 41-year
      old woman who presented with a 3-year history of left aural fullness associated
      with ipsilateral "hammer beating" tinnitus. Patient 2 was a 41-year-old male who
      presented with unilateral conductive hearing loss. CONCLUSION:  Adenoma with
      neuroendocrine differentiation of the middle ear is a rare entity, but it should
      be considered in patients with tinnitus, aural fullness, and a retrotympanic mass
      and remembered as a diferential diagnosis of tympanic paraganglioma.

PMID- 25992032
TI  - Bullous Systemic Lupus Erythematosus: Case report.
AB  - INTRODUCTION:  Bullous systemic lupus erythematosus (BSLE) is an autoantibody
      mediated disease with subepidermal blisters. It is a rare form of presentation of
      SLE that occurs in less than 5% of cases of lupus. CASE REPORT:  A 27-year-old,
      female, FRS patient reported the appearance of painful bullous lesions in the
      left nasal wing and left buccal mucosa that displayed sudden and rapid growth.
      She sought advice from emergency dermatology staff 15 days after onset and was
      hospitalized with suspected bullous disease. Intravenous antibiotics and steroids
      were administered initially, but the patient showed no improvement during
      hospitalization. She displayed further extensive injuries to the trunk, axillae,
      and vulva as well as disruption of the bullous lesions, which remained as
      hyperemic scars. Incisional biopsy of a lesion in the left buccal mucosa was
      performed, and pathological results indicated mucositis with extensive erosion
      and the presence of a predominantly neutrophilic infiltrate with degeneration of
      basal cells and apoptotic keratinocytes. Under direct immunofluorescence, the
      skin showed anti-IgA, anti-IgM, and anti-IgG linear fluorescence on the
      continuous dermal side of the cleavage. Indirect immunofluorescence of the skin
      showed conjugated anti-IgA, was anti-IgM negative, and displayed pemphigus in
      conjunction with anti-IgG fluorescence in the nucleus of keratinocytes,
      consistent with a diagnosis of bullous lupus erythematosus. DISCUSSION:  BSLE is
      an acquired autoimmune bullous disease caused by autoantibodies against type VII
      collagen or other components of the junctional zone, epidermis, and dermis. It
      must be differentiated from the secondary bubbles and vacuolar degeneration of
      the basement membrane that may occur in acute and subacute cutaneous lupus
      erythematosus.

PMID- 25992033
TI  - Eagle's Syndrome.
AB  - INTRODUCTION:  Eagle's syndrome is characterized by cervicopharyngeal signs and
      symptoms associated with elongation of the styloid apophysis. This elongation may
      occur through ossification of the stylohyoid ligament, or through growth of the
      apophysis due to osteogenesis triggered by a factor such as trauma. Elongation of
      the styloid apophysis may give rise to intense facial pain, headache, dysphagia,
      otalgia, buzzing sensations, and trismus. Precise diagnosis of the syndrome is
      difficult, and it is generally confounded by other manifestations of
      cervicopharyngeal pain. OBJECTIVE:  To describe a case of Eagle's syndrome. CASE
      REPORT:  A 53-year-old man reported lateral pain in his neck that had been
      present for 30 years. Computed tomography (CT) of the neck showed elongation and
      ossification of the styloid processes of the temporal bone, which was compatible
      with Eagle's syndrome. Surgery was performed for bilateral resection of the
      stylohyoid ligament by using a transoral and endoscopic access route. The patient
      continued to present pain laterally in the neck, predominantly on his left side.
      CT was performed again, which showed elongation of the styloid processes. The
      patient then underwent lateral cervicotomy with resection of the stylohyoid
      process, which partially resolved his painful condition. Final Comments: Patients
      with Eagle's syndrome generally have a history of chronic pain. Appropriate
      knowledge of this disease is necessary for adequate treatment to be provided. The
      importance of diagnosing this uncommon and often unsuspected disease should be
      emphasized, given that correct clinical-surgical treatment is frequently delayed.
      The diagnosis of Eagle's syndrome is clinical and radiographic, and the
      definitive treatment in cases of difficult-to-control pain is surgical.

PMID- 25992035
TI  - New challenges for international archives of otorhinolaryngology.

PMID- 25992034
TI  - Retrolabyrinthine approach for cochlear nerve preservation in neurofibromatosis
      type 2 and simultaneous cochlear implantation.
AB  - INTRODUCTION:  Few cases of cochlear implantation (CI) in neurofibromatosis type
      2 (NF2) patients had been reported in the literature. The approaches described
      were translabyrinthine, retrosigmoid or middle cranial fossa. OBJECTIVES:  To
      describe a case of a NF2- deafened-patient who underwent to vestibular schwannoma
      resection via RLA with cochlear nerve preservation and CI through the round
      window, at the same surgical time. Resumed Report: A 36-year-old woman with
      severe bilateral hearing loss due to NF2 was submitted to vestibular schwannoma
      resection and simultaneous CI. Functional assessment of cochlear nerve was
      performed by electrical promontory stimulation. Complete tumor removal was
      accomplishment via RLA with anatomic and functional cochlear and facial nerve
      preservation. Cochlear electrode array was partially inserted via round window.
      Sound field hearing threshold improvement was achieved. Mean tonal threshold was
      46.2 dB HL. The patient could only detect environmental sounds and human voice
      but cannot discriminate vowels, words nor do sentences at 2 years of follow-up.
      CONCLUSION:  Cochlear implantation is a feasible auditory restoration option in
      NF2 when cochlear anatomic and functional nerve preservation is achieved. The RLA
      is adequate for this purpose and features as an option for hearing preservation
      in NF2 patients.

PMID- 25992036
TI  - Quality, range, and legibility in web sites related to orofacial functions.
AB  - Introduction Plenty of information about health is available on the Internet;
      however, quality and legibility are not always evaluated. Knowledge regarding
      orofacial functions can be considered important for the population because it
      allows proper stimulus, early diagnosis, and prevention of the oral myofunctional
      alterations during early infancy. Objective The aim was evaluate the quality,
      legibility, and range of Web sites available in Brazilian Portuguese regarding
      the orofacial functions. Methods Selected Web sites with information directed to
      parents/caregivers of babies regarding breast-feeding, feeding after 6 months,
      deleterious oral habits, and breathing and speech were studied. The Web sites
      were evaluated through the application of Flesch Reading Ease Test and aspects of
      the Health on the Net (HON) modified code (HONCode); the range of the subjects
      addressed was compared with other aspects of infant development. Results From the
      access of 350 pages of the Internet, 35 Web sites were selected and 315 excluded
      because they did not meet the inclusion criteria. In relation to legibility, Web
      sites scored an average of 61.23% in the Flesch Test, and the application of the
      modified HONCode showed an average of 6.43 points; an average of 2.49 subjects
      were found per Web site evaluated, with information on breast-feeding being more
      frequent and subjects such as breathing and speech less frequent. Conclusions Web
      sites that deal with orofacial functions presented standard legibility
      classification. Only half of the ethical principles were considered by the
      modified HONCode in their majority, and most addressed subjects after "breast
      feeding" were presented with restricted range. 

PMID- 25992037
TI  - Head Position Comparison between Students with Normal Hearing and Students with
      Sensorineural Hearing Loss.
AB  - Introduction Head sense position is coordinated by sensory activity of the
      vestibular system, located in the inner ear. Children with sensorineural hearing
      loss may show changes in the vestibular system as a result of injury to the inner
      ear, which can alter the sense of head position in this population. Aim Analyze
      the head alignment in students with normal hearing and students with
      sensorineural hearing loss and compare the data between groups. Methods This
      prospective cross-sectional study examined the head alignment of 96 students, 48
      with normal hearing and 48 with sensorineural hearing loss, aged between 7 and 18
      years. The analysis of head alignment occurred through postural assessment
      performed according to the criteria proposed by Kendall et al. For data analysis
      we used the chi-square test or Fisher exact test. Results The students with
      hearing loss had a higher occurrence of changes in the alignment of the head than
      normally hearing students (p < 0.001). Forward head posture was the type of
      postural change observed most, occurring in greater proportion in children with
      hearing loss (p < 0.001), followed by the side slope head posture (p < 0.001).
      Conclusion Children with sensorineural hearing loss showed more changes in the
      head posture compared with children with normal hearing. 

PMID- 25992038
TI  - Prevalence of contralateral hearing aid use in adults with cochlear implants.
AB  - Introduction The exclusive use of a cochlear implant (CI) in one ear allows
      patients to effectively hear speech in a quiet environment. However, in
      environments with competing noise, the processing of multiple sounds becomes
      complex. In an attempt to promote binaural hearing in a noninvasive manner, the
      use of a hearing aid in the nonimplanted ear is suggested for patients with a
      unilateral CI. Aims To identify the prevalence of hearing aid use in the
      contralateral ear in adults who already have a CI; to determine the reasons why
      some patients do not use contralateral hearing aids (CHAs); and to analyze the
      effects of residual hearing in CHA users. Materials and Methods This is a
      clinical study in 82 adult patients with CI implants who responded to a
      questionnaire designed to determine current use of CHA. Results In our patient
      sample, 70 CHA nonusers were identified. The prevalence of CHA users was
      determined to be 12% with a 95% confidence interval of 11 to 13%. About 58.2% of
      the CHA nonusers reported a lack of noticeable benefit even after wearing hearing
      aids, and 23.6% reported not having received the option to use a CHA. CHA users
      had a pure tone average of 107-dB hearing level, whereas CHA nonusers had a pure
      tone average of 117-dB hearing level. Conclusion The prevalence of the use of a
      CHA is low in our study. We attribute the low use of a CHA to either a lack of
      residual hearing or to a lack of benefit from the amplification. 

PMID- 25992039
TI  - Allergen-specific immunotherapy in patients 55 years and older: results and
      review of literature.
AB  - Introduction Over the years the immune system suffers many morphologic and
      functional alterations, which result in a peak of function in puberty and a
      gradual decrease in the elderly. Aim Treat patients 55 years or older with
      allergic rhinitis with immunotherapy and then analyze the response to allergens.
      Materials and Methods From June 2009 to July 2010, 104 charts of patients 55
      years or older with allergic complaints were evaluated. The patients were
      selected by anamnesis, physical examination, and otorhinolaryngologic exam. The
      patients had cutaneous test for mites before and after 1 year of sublingual
      specific immunotherapy. The cutaneous response was classified as negative
      (absent), light, moderate, or severe. Results Before vaccination, 42 (40.4%)
      patients were classified as having a severe form of allergy and 62 (59.6%) as
      having a moderate allergy. After the specific therapy, 40 (38.4%) patients were
      classified as negative (absent), 37 (35.6%) as light, 19 (18.3%) as moderate, and
      8 (7.7%) as severe responses. Conclusion Immunotherapy, a desensitization
      technique, is indicated in cases which patients cannot avoid the exposure to
      allergens and in situations where pharmacologic therapy is not ideal. Specific
      immunotherapy to treat the allergic rhinitis in elderly patients was efficient
      and had no collateral effects, and in addition to the clinical benefit,
      improvement in the cutaneous test could also be observed. 

PMID- 25992040
TI  - Vector electronystagmography analysis in elderly individuals with dizziness
      complaint.
AB  - Introduction Vector electronystagmography is widely used to evaluate vestibular
      function; however, elderly patients may show changes not due to vestibular
      disorders. Aim This study aims to characterize vector electronystagmography tests
      in the elderly participants in a service station of the Brazilian public health
      system, the Unified Health System (SUS) in the city of Natal, who presented with
      dizziness. Methods A cross-sectional and clinical study to characterize the
      vector electronystagmography in 10 members of an elderly SUS referral center
      located in the city of Natal with dizziness. Results Of 10 patients interviewed,
      9 were women, and just 1 was a man. All complained of dizziness in the last year,
      and most of them had more than one type of dizziness. The main differential
      diagnosis was benign paroxysmal positional vertigo. Regarding vector
      electronystagmography, we found 20% of patients with semispontaneous nystagmus in
      at least one direction and changes in saccades latency in 100% of patients, with
      20% in relation to the accuracy of pendular tracking changes at the frequency of
      0.2 Hz, 10% at 0.4 Hz, and 80% at 0.8 Hz, and 10% change in optokinetic gain. No
      patient had altered caloric test. Conclusion Vector electronystagmography
      alterations in the elderly do not always indicate disease. 

PMID- 25992041
TI  - Characterization of swallowing sounds with the use of sonar Doppler in full-term
      and preterm newborns.
AB  - Introduction Technological advances have provided a large variety of instruments
      to view the swallowing event, aiding in the evaluation, diagnosis, and monitoring
      of disturbances. These advances include electromyography of the surface, dynamic
      video fluoroscopy, and most recently sonar Doppler. Objective To characterize
      swallowing sounds in typical children through the use of sonar Doppler. Method
      Thirty newborns participated in this prospective study. All newborns received
      breast milk through either their mother's breasts or bottles during data
      collection. The newborns were placed in either right lateral or left lateral
      positions when given breast milk through their mother's breasts and in a sitting
      position when given a bottle. There were five variables measured: initial
      frequency of sound wave (FoI), frequency of the first peak of the sound wave
      (FoP1), frequency of the second peak of the sound wave (FoP2), initial intensity
      and final sound wave (II and IF), and swallowing length (T), the time elapsed
      from the beginning until the end of the analyzed acoustic signal measured by the
      audio signal, in seconds. Results The values obtained in the initial frequency of
      the babies had a mean of 850 Hz. In terms of frequency of first peak, only three
      presented with a subtle peak, which was due to the elevated larynx position.
      Conclusion The use of sonar Doppler as a complementary exam for clinical
      evaluations is of upmost importance because it is nonintrusive and painless, and
      it is not necessary to place patients in a special room or expose them to
      radiation. 

PMID- 25992042
TI  - Are histologic studies of adenotonsillectomy really necessary?
AB  - Introduction In most ear, nose, and throat services, it is routine to send the
      material extracted from tonsillectomy for histologic study to research
      malignancy, to analyze suspect material, or to provide medical-legal
      documentation. Recent studies have shown that this routine analysis is
      dispensable. Objective To evaluate the actual need and perform a cost-benefit
      analysis of routine histopathologic examination in tonsillectomy with no signs or
      symptoms of malignancy. Methods A retrospective observational study evaluated the
      charts of patients undergoing adenotonsillectomy, tonsillectomy, or adenoidectomy
      from January 2008 to September 2009 at the Institute of Otorhinolaryngology CEMA
      SP. Costs of this test for the public health system were analyzed and the
      literature reviewed. Results We studied 281 patients between 2 and 22 years of
      age; 142 (50.5%) were male and 139 (49.5%) were female. Of the surgeries, 201
      were adenotonsillectomies (71.5%), 41 were tonsillectomies (14.5%), and 39 were
      adenoidectomies (14%). The most common indication for surgery was recurrent
      infection (63.3%). None of study patients had clinical suspicion of malignancy.
      The tests showed a cost of R$20.03 per tonsil analyzed. Conclusion Routine
      histopathologic examination in patients undergoing adenotonsillectomy with no
      signs or symptoms of malignancy is dispensable and increases the cost of the
      surgeries. 

PMID- 25992043
TI  - A descriptive epidemiology study of oral cleft in sergipe, Brazil.
AB  - Introduction The nonsyndromic orofacial cleft is the fourth most common birth
      defect, but in Brazil, data about the cleft epidemiology are not accurate.
      Objective This study aimed to describe the epidemiologic characteristics of oral
      cleft cases at Specialized Society Attending Cleft Patient in Sergipe State.
      Methods Data were obtained from patients' medical records in relation to the
      following characteristics: age; gender; race; origin; cleft type; additional
      malformations and/or complications; prenatal accomplishment; treatment applied.
      For diagnosis analysis, it was noted if mothers had received prenatal care and if
      they had ultrasonography performed and if the cleft was viewed in it. Results We
      observed a prevalence of male gender (54%). Age between 0 and 4 years old was
      most prevalent (53%), and pheoderma race was observed in 47%. Transincisive
      foramen cleft was found in 52.3% of the individuals. The prevalence of pre- and
      transincisive foramen cleft was higher in men (66.3 and 55.7%), women accounted
      for 65.0% of postincisive foramen, and atypical facial cleft (0.3%) occurred in
      one case. Associated malformations and complications were present in 12% of
      patients. Prenatal care was reported by 48% of the mothers. Conclusion In this
      study male gender was the most affected, and 0 to 4 years was the most frequent
      age group. Transincisive foramen cleft type was most frequently encountered.
      Prenatal care was reported by most mothers. So, this study found that early
      treatment is a reality in SEAFESE (Service Specializing in Cleft Care of
      Sergipe), and consequently the chances of successful integration of the child to
      society will be better. 

PMID- 25992044
TI  - Tympanometry in infants: a study of the sensitivity and specificity of 226-Hz and
      1,000-Hz probe tones.
AB  - Introduction For infants under 6 months, the literature recommends 1,000-Hz
      tympanometry, which has a greater sensitivity for the correct identification of
      middle ear disorders in this population. Objective To systematically analyze
      national and international publications found in electronic databases that used
      tympanometry with 226-Hz and 1,000-Hz probe tones. Data Synthesis Initially, we
      identified 36 articles in the SciELO database, 11 in the Latin American and
      Caribbean Literature on the Health Sciences (LILACS) database, 199 in MEDLINE, 0
      in the Cochrane database, 16 in ISI Web of Knowledge, and 185 in the Scopus
      database. We excluded 433 articles because they did not fit the selection
      criteria, leaving 14 publications that were analyzed in their entirety.
      Conclusions The 1,000-Hz tone test has greater sensitivity and specificity for
      the correct identification of tympanometric curve changes. However, it is
      necessary to clarify the doubts that still exist regarding the use of this test
      frequency. Improved methods for rating curves, standardization of normality
      criteria, and the types of curves found in infants should be addressed. 

PMID- 25992045
TI  - Rehabilitation with cochlear implant in patient with harboyan syndrome.
AB  - Background Harboyan syndrome, defined as congenital corneal dystrophy associated
      with progressive sensorineural hearing loss, was first described by Harboyan in
      1971. It is a hereditary disease manifested by eye lesions consistent with
      corneal endothelial dystrophy and progressive sensorineural hearing loss. There
      is bilateral symmetric progressive hearing loss, which may be either dominant or
      recessive. Objective To report a case of a patient with a diagnosis of Harboyan
      syndrome. Case Report A 25-year-old woman with profound bilateral sensorineural
      hearing loss, showing poor hearing performance while using a personal sound
      amplification device, underwent hearing rehabilitation with a cochlear implant.
      Conclusion Rehabilitation was imperative in this case. The cochlear implant has
      proven to be the best therapeutic option, providing the patient with a better
      quality of life. 

PMID- 25992046
TI  - Dermoid of the nasopharynx causing neonatal respiratory distress.
AB  - The dermoid is a rare and benign malformation of bigerminal origin. It is seen
      frequently in the neonatal period, and the clinical presentation depends on the
      site and on the size of the lesion, and the classical clinical picture is of a
      tumor derived from the naso- or oropharynx, leading to respiratory distress
      and/or feeding disorders. A female newborn was born cyanotic requiring
      intubation. The oroscopy revealed a large smooth mass. Transoral surgery was
      performed with successful extubation. Seven months after, there are no signs of
      recurrence of the lesion. This report adds another case of this rare pathology
      that can be life-threatening condition in the neonate. It emphasizes the
      importance of dermoid in the differential diagnosis of the naso- or oropharyngeal
      lesions, especially in neonates. 

PMID- 25992047
TI  - Stage II Chronic Maxillary Atelectasis Associated with Subclinical Visual Field
      Defect.
AB  - Introduction Chronic maxillary atelectasis (CMA) is characterized by a persistent
      decrease in the maxillary sinus volume due to inward bowing of its walls.
      According to its severity, it may be classified into three clinical-radiological
      stages. Objective To report a case of stage II CMA associated with subclinical
      visual field defect. Case Report A 34-year-old woman presented with a 15-year
      history of recurrent episodes of sinusitis and intermittent right facial
      discomfort for the past 5 years. She denied visual complaints, and no facial
      deformities were observed on physical examination. Paranasal sinus computed
      tomography (CT) demonstrated a completely opacified right maxillary sinus with
      inward bowing of its walls, suggesting the diagnosis of stage II CMA. A
      computerized campimetry (CC) disclosed a scotoma adjacent to the blind spot of
      the right eye, indicating a possible damage to the optic nerve. The patient was
      submitted to functional endoscopic sinus surgery, with drainage of a thick mucous
      fluid from the sinus. She did well after surgery and has been asymptomatic since
      then. Postoperative CT was satisfactory and CC was normal. Discussion CMA occurs
      because of a persistent ostiomeatal obstruction, which creates negative pressure
      inside the sinus. It is associated with nasosinusal symptoms but had never been
      described in association with any visual field defect. It can be divided into
      stage I (membranous deformity), stage II (bony deformity), and stage III
      (clinical deformity). The silent sinus syndrome is a special form of CMA. This
      term should only be used to describe those cases with spontaneous enophthalmos,
      hypoglobus, and/or midfacial deformity in the absence of nasosinusal symptoms. 

PMID- 25992048
TI  - Human syngamosis as an uncommon cause of chronic cough.
AB  - Introduction Chronic cough may represent a diagnostic challenge. Chronic
      parasitism of upper airways is an unusual cause. Objective To describe a case of
      human syngamosis as an uncommon cause of dry cough. Case Report An endoscopic
      exam performed in a woman suffering of chronic cough revealed a Y-shaped worm in
      the larynx identified as Syngamus laryngeus. Discussion This nematode parasitizes
      the upper respiratory tract of many animals including humans. The diagnosis is
      performed by the examination of the worm expelled by cough or by endoscopy.
      Endoscopic exam is easy to perform and is essential in the diagnosis of causes of
      chronic cough, even uncommon entities. Removal is the only efficient treatment. 

PMID- 25992049
TI  - Adult rhabdomyoma of the larynx.
AB  - Introduction Rhabdomyoma is a rare benign tumor derived from skeletal muscles.
      Laryngeal rhabdomyomas are even rarer, with only approximately 40 reported cases
      in world literature. Laryngeal rhabdomyomas usually are seen as masses covered by
      mucosa. They are often solitary asymptomatic tumors, but symptoms such as
      hoarseness can occur. The radiologic features are usually those typical of benign
      neoplasms, showing well-delineated borders. The differential diagnoses for
      laryngeal masses include cysts, laryngoceles, and benign and malignant neoplasms.
      The diagnosis is usually made using histopathologic findings, but in some cases
      some difficulties can be found. Immunohistochemical staining is of great value in
      the differentiation of similar tumors. Treatment of rhabdomyoma is surgical
      excision. Objective To describe a case of rhabdomyoma of the larynx attended at
      Santa Casa de Misericordia do Rio de Janeiro. Case Report A 35-year-old man
      presented with progressive hoarseness in the preceding year. Laryngoscopy showed
      a large submucosal tumor at the supraglottic region of the larynx. The neck
      computed tomography scan confirmed the submucosal mass, with distinct borders.
      The patient was taken to the operating suite, where endoscopic extirpation of the
      mass was performed. Initial histologic diagnosis was suggestive of paraganglioma,
      which was not confirmed by studies with immunohistochemical markers, and
      diagnosis was changed to adult-type rhabdomyoma. The patient recovered well. His
      voice returned to normal after 3 months. Discussion Although muscle tumors of the
      larynx are very rare, rhabdomyoma should be considered when there is a submucosal
      mass in the larynx. 

PMID- 25992050
TI  - Atypical manifestation of vestibular schwannoma.
AB  - Introduction Vestibular schwannoma (also known as acoustic neuroma) is a benign
      tumor whose cells are derived from Schwann sheaths, which commonly occurs from
      the vestibular portion of the eighth cranial nerve. Furthermore, vestibular
      schwannomas account for ~8% of intracranial tumors in adults and 80 to 90% of
      tumors of the cerebellopontine angle. Its symptoms are varied, but what stands
      out most is a unilateral sensorineural hearing loss, with a low index of speech
      recognition. Objective Describe an atypical manifestation of vestibular
      schwannoma. Case Report The 46-year-old woman had vertigo and binaural hearing
      loss and fullness, with ear, nose, and throat examination suggestive of cochlear
      injury. After 6 months, the patient developed worsening of symptoms and onset of
      right unilateral tinnitus. In further exams the signs of cochlear damage
      remained, except for the vestibular test (hyporeflexia). Magnetic resonance
      imaging showed an expansive lesion in the right cerebellopontine angle.
      Discussion This report warns about the atypical manifestations of vestibular
      schwannoma, which must always be remembered in investigating and diagnosing
      hearing loss. 

PMID- 25992051
TI  - Giant nasolabial cyst treated using neumann incision: case report.
AB  - Introduction A nasolabial cyst is an ectodermal development cyst. It presents as
      a fullness of canine fossa, nasal ala, or vestibule of the nose. It is rare and
      usually small. Treatment consists of complete surgical excision or transnasal
      endoscopic marsupialization. Objective To describe a giant nasolabial cyst case
      treated using Neumann incision. Case Report A 37-year-old man was referred to the
      otolaryngology department with nasal obstruction and nasal deformity. Computed
      tomography showed a nasal cystic lesion 4 * 4.5 * 5 cm wide. Surgical excision
      using Neumann incision was performed. Discussion Neumann incision provides wide
      access to the nasal cavity and may be useful in nasolabial cyst treatment. 

PMID- 25992052
TI  - Cochlear Implants in Children Diagnosed with CHARGE Syndrome.
AB  - Introduction The CHARGE association (coloboma of the eyes; heart disease; atresia
      of the choanae; retarded growth and development; genital hypoplasia/genitourinary
      anomalies; ear anomalies and/or hearing loss) was first described in 1979 by
      Hall, and among its main features is hearing loss. This study presents a case
      aiming to establish relationships between performance on Infant Toddler
      Meaningful Auditory Integration Scale (IT-MAIS) and Meaningful Use of Speech
      Scales (MUSS) tests and the analysis of hearing and language categories of a
      patient diagnosed with CHARGE syndrome, before and after cochlear implant (CI)
      surgery. Case Report A 7-year-old girl was diagnosed with CHARGE. She had severe
      sensorineural hearing loss and was a prelingual unilateral CI user. We analyzed
      data from the patient's medical records regarding therapies and video recordings.
      Results The patient showed positive results in all evaluations after CI. IT-MAIS
      rose from 5 to 90% following the use of CI. MUSS also rose, from 75 to 72.5%,
      after use of CI. Classification of Auditory Skills changed from category 1 before
      use of CI to category 6 after use of CI. Classification of Language Skills
      changed from category 1 before use of CI to category 3 after use of CI. The CI is
      an aid but there are many factors in the therapeutic process, and great
      heterogeneity in individuals diagnosed with CHARGE should be investigated.
      Conclusion The development of listening and language skills after CI use was
      demonstrated by IT-MAIS and MUSS tests, and categorization of speech and hearing
      in this child with a diagnosis of CHARGE syndrome shows that CI can be an
      effective technological resource to provide information on hearing as one source
      for language construction. 

PMID- 25992053
TI  - Breaking barriers.

PMID- 25992054
TI  - Retrospective study of a series of choanal atresia patients.
AB  - Introduction Although it has been more than 250 years since the first description
      of choanal atresia (CA), there are still doubts about this abnormality. The
      differences between unilateral and bilateral forms are seldom discussed.
      Objectives Aggregate data from patients diagnosed with CA, grouping patients with
      unilateral and bilateral forms. Methods Retrospective study. Results Eighteen
      patients were included: 12 (66.6%) presented bilateral atresia, of which 77.8%
      were mixed bony-membranous type and 22.2% were pure bony type. From the 12
      patients with bilateral atresia, 10 presented related malformations, 3 of whom
      had CHARGE syndrome (coloboma, heart defects, choanal atresia, retardation of
      growth and development, genitourinary problems, ear abnormalities). From the
      remaining 6 patients with unilateral atresia, only 2 showed malformations, 1
      renal and 1 cardiac. All patients with unilateral atresia needed only 1 surgical
      procedure, and patients with the bilateral form needed a median of 2.85
      interventions (p = 0.003). The median age of surgical procedure in the unilateral
      group was 6 years, ranging from 6 months to 18 years, and in the bilateral group
      was 25 days, ranging from 6 days to 6 years (p = 0.003). The median interval
      between diagnosis and surgery was 9 months in the unilateral group, ranging from
      1 month to 18 years, and in the bilateral group was 1 day, ranging from 1 day to
      2 months (p = 0.001). Discussion and Conclusions Success rates with the
      endoscopic approach vary from 62 to 100%. Nonetheless, most of these reports
      present results without considering the number of compromised sides. In our
      opinion, unilateral and bilateral cases involve distinct patients (taking into
      account the related malformations), have diverging clinical presentations, and
      show discrepant restenosis rates and therefore could be considered in different
      groups of analysis. 

PMID- 25992055
TI  - Otoneurologic findings in a fishermen population of the state of santa catarina:
      preliminary study.
AB  - Introduction Fishing, one of the oldest productive activities, is an important
      sector of the national and world economy. Aim To evaluate the vestibular behavior
      in a population of fishermen. Methods In a retrospective and cross-sectional
      study, 13 fishermen (mean 45.0), between 33 and 62 years of age, were submitted
      to anamnesis, otorhinolaryngological evaluation, and vestibular exam through the
      vector electronystagmography. Results The most evident otoneurologic symptoms
      were hearing loss (76.9%), tinnitus (61.7%), dizziness (46.1%), and headache
      (46.1%). The most evident clinical symptoms were fatigue (46.1%), depression
      (23.0%), anxiety (15.3%), insomnia (7.7%), and agitation during sleep (7.7%).
      There were alterations in the vestibular exam in 5 fishermen (38.5%) discovered
      in the caloric test. There was a prevalence of alteration in the peripheral
      vestibular system. There was a major frequency of the peripheral vestibular
      irritative syndrome. Conclusion The otoneurologic complaints were frequent in the
      population studied to verify the importance of allowing labyrinth exams and the
      need for adopting preventive measures relating to noise exposure as well as
      carbon monoxide exposure, because they can cause and/or enhance various
      manifestations of labyrinthine vestibular impairment that can affect the quality
      of life of these workers. 

PMID- 25992056
TI  - Association between Lung Function and Vocal Affections Arising from Tobacco
      Consumption.
AB  - Introduction Smoking is a major risk factor for numerous diseases; it is
      necessary to analyze the impact that the habit can have on vocal health.
      Objectives To determine the influence of smoking on changes in vocal production
      and lung vital capacity compared with nonsmokers. Methods This cross-sectional
      study compared smokers and nonsmokers (24 subjects each). Each participant
      underwent a vocal and spirometric evaluation to measure vital lung capacity.
      Results The results showed a worsening in lung vital capacity and other
      parameters of voice in smokers compared with nonsmokers. Furthermore, the
      decreased pulmonary vital capacity affected the evaluated voice parameters, and
      decreased carrying capacity was closely related to smoking. The time and amount
      of consumption had a direct relationship with the vocal and maximum phonation
      time. Conclusions This study showed that smoking causes voice disorders due to
      lung weakness. Thus, voice changes are affected both directly by interference of
      smoking on vocal structures and indirectly by increased weakness, which impairs
      lung vocal production. 

PMID- 25992057
TI  - Long latency auditory evoked potential in term and premature infants.
AB  - Introduction The research in long latency auditory evokes potentials (LLAEP) in
      newborns is recent because of the cortical structure maturation, but studies note
      that these potentials may be evidenced at this age and could be considered as
      indicators of cognitive development. Purpose To research the exogenous potentials
      in term and premature infants during their first month of life. Materials and
      Methods The sample consisted of 25 newborns, 15 term and 10 premature infants.
      The infants with gestational age under 37 weeks were considered premature. To
      evaluate the cortical potentials, the infants remained in natural sleep. The
      LLAEPs were researched binaurally, through insertion earphones, with frequent
      /ba/ and rare /ga/ speech stimuli in the intensity of 80 dB HL (decibel hearing
      level). The frequent stimuli presented a total of 80% of the presentations, and
      the rare, 20%. The data were statistically analyzed. Results The average
      gestational age of the term infants was 38.9 weeks (+/- 1.3) and for the
      premature group, 33.9 weeks (+/- 1.6). It was possible to observe only the
      potentials P1 and N1 in both groups, but there was no statistically significant
      difference for the latencies of the components P1 and N1 (p > 0.05) between the
      groups. Conclusion It was possible to observe the exogenous components P1 and N1
      of the cortical potentials in both term and preterm newborns of no more than 1
      month of age. However, there was no difference between the groups. 

PMID- 25992058
TI  - Sensitivity and specificity of portable hearing screening in middle-aged and
      older adults.
AB  - Introduction Hearing screening allows the identification of individuals with
      hearing loss. Aim To determine the sensitivity and specificity of a portable
      hearing screening device in middle-aged and older adults using the manufacturer
      scoring and a scoring system proposed by the researchers. Methods In this
      transversal study, participants underwent anamnesis, otoscopy, and hearing
      screening using portable equipment. After this, a pure tone audiometry was
      performed, with participants classified into two groups: with and without hearing
      loss. The sensitivity and specificity of the hearing screening were calculated
      for the right and left ears using two methods of interpretation: the original
      method recommended by the manufacturer (criteria 1) and the method proposed by
      researchers (criteria 2). Results The sample consisted of 55 individuals, 83.6%
      (n = 46) of whom were women. Per criteria 1, the sensitivities were 26.3 (right
      ear) and 21.4% (left ear). The specificity was 100% for both ears. Using criteria
      2, the sensitivity was 94.7 (right ear) and 100% (left ear). The specificity was
      74.3 (right ear) and 65.9% (left ear). Conclusion This study showed that the
      criteria proposed by the manufacturer presented low sensitivity in the hearing
      screening. The criteria proposed by the researchers to achieve a more efficient
      performance reached high and balanced values for sensitivity and specificity. 

PMID- 25992059
TI  - Can peripheral hearing justify the speech disorders in children with operated
      cleft palate?
AB  - Introduction Any impairment in the hearing ability of a child with cleft lip and
      palate may cause difficulties in receptive and expressive language. Purpose Check
      the association between velopharyngeal dysfunction (VPD), compensatory
      articulation (CA), and peripheral hearing loss in children with cleft palate
      surgery. Methods Retrospective study with 60 children (group 1: presence of VPD
      and CA; group 2: absence of VPD, presence of CA; group 3: presence of VDP,
      absence of CA; group 4: absence of VPD and CA), age 4 to 5 years old, with cleft
      palate surgery, through the analysis of the hearing, VP, and speech evaluations.
      Results Group 4 presented 80% normal hearing; group 1 had 60% hearing loss. The
      conductive hearing loss type was the most frequent. The glottal stop was the most
      frequent in group 1 and the middorsum palatal plosive in group 2. There was no
      significant association (p = 0.05) between hearing loss and the presence of
      compensatory articulations (groups 2 and 4), nor between hearing loss and the
      presence of VPD (groups 3 and 4; p = 0.12). Statistical significance (p = 0.025)
      was found when the group with VPD was associated with the group with CA, that is,
      group 1 with the control group (group 4). Conclusion Significant association
      between peripheral hearing loss, compensatory articulations, and VPD was verified
      for the children in group 1, which not only presented compensatory articulations
      but also VPD. 

PMID- 25992060
TI  - Laser endoscopic microsurgery of laryngeal cancers.
AB  - Introduction The aim of our study is to present our experience in treating
      laryngeal cancers with endoscopic CO2 laser surgery. Materials and Methods This
      retrospective study was conducted from January 2008 to December 2012 at Antoine
      Lacassagne Center of Nice. The functional and oncologic results of this surgical
      technique were analyzed and discussed. Results The average length of hospital
      stay was 2.5 days. Phonatory results were considered excellent in 75% of our
      patients who maintained satisfactory phone communication skills after their
      interventions. Chronic hoarseness was the most common reason for bilateral or
      extended cordectomies. On the oncologic basis, histologic exam showed 90% of our
      margins were normal. The clinical control showed excellent laryngeal preservation
      in 94.23%. In 5 years, the overall survival was estimated at 96.15%. Conclusion
      This study shows the benefit of the laser endoscopic microsurgery for the
      preservation of laryngeal functions and the local histologic control, essentially
      for early stage laryngeal cancers. 

PMID- 25992061
TI  - Balloon laryngoplasty for subglottic stenosis caused by orotracheal intubation at
      a tertiary care pediatric hospital.
AB  - Introduction In recent years, there has been a reduction in mortality rates in
      neonatal intensive care units (NICUs) due to the impact of modern technological
      advances in the perinatal field. As a consequence, prolonged orotracheal
      intubation is used more frequently, and there has been an increase in acquired
      subglottic stenosis (SGS) in children. Subglottic stenosis is a narrowing of the
      endolarynx and one of the most common causes of stridor and respiratory distress
      in children. The laryngoplasty balloon has proven effective in dealing with
      stenosis both as primary and secondary treatments, after open surgery, with the
      added advantage of being less invasive and not requiring external access.
      Materials and Methods This study involved children from pediatric intensive care
      units or NICUs suffering from respiratory distress and who presented an
      endoscopic diagnosis of Myer and Cotton grade I to III SGS. These patients
      underwent balloon laryngoplasty with different numbers of interventions depending
      on the response in each individual case. Results All the patients responded
      satisfactorily to the balloon laryngoplasty. None required tracheostomy after
      treatment and all remained asymptomatic even after 6-month follow-up. One patient
      required just 1 dilation, 4 required 2, 3 underwent the procedure 3 times, and
      another had 5 dilations. Conclusion The experience presented here is that of
      balloon laryngoplasty post-orotracheal intubation SGS with very satisfactory
      results at a tertiary care pediatric hospital. Although the number of patients is
      limited, our incidence corroborates other studies that demonstrate the efficacy
      and safety of balloon dilatation in the treatment of SGS. 

PMID- 25992062
TI  - Newborn hearing screening in neonates exposed to psychoactive drugs.
AB  - Introduction In pregnancy, the mother and fetus share body structures based on
      the maternal organism. Exposure to psychoactive drugs in this period may have
      repercussions on the baby's hearing. Therefore, it is necessary to investigate
      this association. Aim Analyze the results of newborn hearing screening (NHS), the
      occurrence of associated risk factors, and the incidence of hearing loss in
      newborn exposed to psychoactive drugs during pregnancy. Methods This is an
      observational retrospective study done from a database analysis. From this
      database, records were selected about the use of psychoactive drugs by mothers
      during pregnancy, then the neonates were divide into two groups: the study group
      (146 babies exposed to drugs) and the control group (500 babies not exposed to
      drugs). The NHS failure rate, the presence of risk factors for hearing loss, and
      need for audiological diagnosis were analyzed in both groups. From these
      variables, absolute frequency and prevalence rates were calculated and the
      results compared between groups. Results There was no statistically significant
      difference in the comparison of NHS failure rates between the groups (p = 0.267).
      The occurrence of risk factors for hearing loss was greater in babies exposed to
      drugs (p < 0.0001). There was only one diagnosis of hearing loss, which occurred
      in the control group (p = 0.667). Conclusion The use of psychoactive drugs by
      mothers during pregnancy did not affect the NHS failure rate of this sample.
      However, the occurrence of significant risk factors in the study group showed a
      possible sensitivity of babies exposed to psychoactive drugs during pregnancy. 

PMID- 25992063
TI  - Probable Correlation between Temporomandibular Dysfunction and Vertigo in the
      Elderly.
AB  - Introduction Temporomandibular disorder (TMD) covers a variety of clinical
      problems, and some epidemiologic studies have tried to indicate mechanisms of
      interaction and association between vertigo and TMD, but this topic still is
      controversial. Objective To assess the presence of vertigo in elderly patients
      associated with TMD. Methods A cross-sectional study was conducted with the
      inclusion of elderly individuals who lived independently. TMD was assessed by
      dental evaluation and vertigo was verified by medical history. Statistical
      analysis was performed using the chi-square and relative risk. Results There was
      a significant association (p = 0.0256) between the TMD and vertigo (odds ratio =
      2.3793). Conclusion These results highlighted the importance of identifying risk
      factors for vertigo that can be modified through specific interventions, which is
      essential to prevent future episodes, as well as managing the process of
      rehabilitation of elderly patients in general. 

PMID- 25992064
TI  - Demystifying septoplasty in children.
AB  - Introduction Septum deviation in children may alter the early physiologic process
      of breathing, causing obligatory oral breathing and consequently changing
      craniofacial development and even intellect. Because of these consequences,
      septoplasty should be performed as early as possible. Materials and Methods The
      retrospective study reviewed the results of septoplasty in 40 children under 12
      years old who had follow-up after surgery for a maximum period of 7 years. The
      research was submitted to the ethics committee and approved with protocol number
      10331912.0.0000.0058. Results Forty patients underwent septoplasty, 39 (97.5%)
      had cauterization of inferior turbinate and associated procedure, 20 (50%) had
      adenotonsillectomy, and 17 (42.5%) had adenoidectomy. Conclusion Nasal septum
      deviation should be corrected early to provide the harmonious growth of the face
      and to enable normal development of the child, without the occurrence of nasal
      deformity. 

PMID- 25992065
TI  - A Cephalometric Analysis for Evaluation of Changes in Soft Tissues in the Regions
      of the Upper and Lower Lips and Chin due to Orthognathic Maxillary Advancement
      Surgery.
AB  - Introduction There is currently no consensus regarding the best method for
      predicting the changes in soft tissues due to the modification of hard tissues in
      orthognathic surgery. Objective To measure the changes in soft tissues of the
      upper lip, lower lip, and chin regions due to the modifications of hard tissues
      caused by orthognathic maxillary advancement surgery using a cephalometric
      methodology. Methods The study was conducted on 35 patients with dentoskeletal
      and facial deformities submitted to orthognathic maxillary advancement surgery.
      Two teleradiographs were taken: one during the preoperative period and the other
      1 year after the surgery, on which the cephalometric tracing was drawn. Results A
      strong correlation (r = 0.747) was demonstrated in the horizontal analysis
      between the hard A (Ah) point (located in the deepest point of the anterior
      curvature of the maxilla) and the soft A (As) point in the advancement of the
      maxilla, with a mean variation of 0.859% occurring in As with each 1% variation
      of the Ah point. A mean variation of 0.698% occurred in the superior soft
      prostion point (prolongation of the superior hard prostion point to its
      corresponding point on soft tissue) for each 1% variation in the superior hard
      prostion point (bone point located at the junction of the alveolar process with
      the crown of the upper incisors). Conclusion The cephalometric methodology
      applied here revealed that the soft tissues of the upper lip accompanied 70 to
      80% of the movement of hard tissues in maxillary advancement and that the soft
      tissues of the lower lip did not change or showed no significant changes. 

PMID- 25992066
TI  - Cadaveric temporal bone dissection: is it obsolete today?
AB  - Introduction Traditionally, surgical training in otology, is imparted by
      dissecting harvested human cadaveric temporal bones. However, maintenance of a
      cadaveric temporal bone laboratory is expensive and carries risk of exposure to
      infection. In recent times, other modalities of training are gaining ground and
      are likely to eventually replace cadaveric temporal bone dissection altogether.
      Objectives Other alternative methods of training are emerging. New technology
      like simulation and virtual reality as high-fidelity, safer alternatives, are
      making rapid strides as teaching tools. Other options are the use of animal
      temporal bones as teaching tools. The advantages of these are compared. Data
      Synthesis None of these modalities can replicate the innumerable anatomical
      variations which are a characteristic feature of the human temporal bone. A
      novice surgeon not only needs exposure to surgical anatomy and it's variations
      but also needs to develop hand-eye coordination skills to gain expertise.
      Conclusion Deliberate practice on human cadaveric temporal bones only, will
      confer both mastery in anatomy and surgical technique. The human cadaveric
      temporal bone is ideal simulator for training in otology. 

PMID- 25992067
TI  - Anatomical Changes and Audiological Profile in Branchio-oto-renal Syndrome: A
      Literature Review.
AB  - Introduction Branchio-oto-renal (BOR) syndrome is an autosomal-dominant genetic
      condition with high penetrance and variable expressivity, with an estimated
      prevalence of 1 in 40,000. Approximately 40% of the patients with the syndrome
      have mutations in the gene EYA1, located at chromosomal region 8q13.3, and 5%
      have mutations in the gene SIX5 in chromosome region 19q13. The phenotype of this
      syndrome is characterized by preauricular fistulas; structural malformations of
      the external, middle, and inner ears; branchial fistulas; renal disorders; cleft
      palate; and variable type and degree of hearing loss. Aim Hearing loss is part of
      BOR syndrome phenotype. The aim of this study was to present a literature review
      on the anatomical aspects and audiological profile of BOR syndrome. Data
      Synthesis Thirty-four studies were selected for analysis. Some aspects when
      specifying the phenotype of BOR syndrome are controversial, especially those
      issues related to the audiological profile in which there was variability on
      auditory standard, hearing loss progression, and type and degree of the hearing
      loss. Mixed loss was the most common type of hearing loss among the studies;
      however, there was no consensus among studies regarding the degree of the hearing
      loss. 

PMID- 25992068
TI  - Ocular vestibular evoked myogenic potentials.
AB  - Introduction Diagnostic testing of the vestibular system is an essential
      component of treating patients with balance dysfunction. Until recently, testing
      methods primarily evaluated the integrity of the horizontal semicircular canal,
      which is only a portion of the vestibular system. Recent advances in technology
      have afforded clinicians the ability to assess otolith function through
      vestibular evoked myogenic potential (VEMP) testing. VEMP testing from the
      inferior extraocular muscles of the eye has been the subject of interest of
      recent research. Objective To summarize recent developments in ocular VEMP
      testing. Results Recent studies suggest that the ocular VEMP is produced by
      otolith afferents in the superior division of the vestibular nerve. The ocular
      VEMP is a short latency potential, composed of extraocular myogenic responses
      activated by sound stimulation and registered by surface electromyography via
      ipsilateral otolithic and contralateral extraocular muscle activation. The
      inferior oblique muscle is the most superficial of the six extraocular muscles
      responsible for eye movement. Therefore, measurement of ocular VEMPs can be
      performed easily by using surface electrodes on the skin below the eyes
      contralateral to the stimulated side. Conclusion This new variation of the VEMP
      procedure may supplement conventional testing in difficult to test populations.
      It may also be possible to use this technique to evaluate previously inaccessible
      information on the vestibular system. 

PMID- 25992069
TI  - Removing nasal packing in epistaxis: what to do in the case of an undeflatable
      foley catheter balloon.
AB  - Introduction Undeflatable Foley catheter balloons adapted for use as nasal
      packing in epistaxis represent a possible complication. Case Reports We report on
      three cases in which Foley catheter balloons adapted for use as posterior nasal
      packing in epistaxis failed to deflate. In one patient, deflation was achieved by
      simply using the fingertips to massage the segment of the catheter collapsed by
      the fixation device. In the second case, the Foley balloon was removed by the
      oral route after sectioning the catheter. In the third patient, the Foley
      catheter was successfully deflated after sectioning. Discussion The probable
      causes of the undeflatable balloons in these cases were a blockage or lumen
      collapse of the balloon or a malfunction in the valve system. Although no
      definitive method has been established for dealing with this complication, the
      options proposed are the following: manipulation to restore the permeability of
      the segment of the catheter collapsed by the fixation device, if this is the
      case; sectioning the catheter or inserting a stiletto catheter; bursting the
      balloon; or removing it by the oral route. The latter option is apparently the
      most appropriate for the otolaryngologist in cases unrelated to simple collapse
      caused by the fixation device. 

PMID- 25992070
TI  - Transpterygoid approach to a dermoid cyst in pterygopalatine fossa.
AB  - Objective To describe a case of dermoid cyst arising from the pterygopalatine
      fossa and review the literature. Methods We report a case of a 23-year-old man
      who suffered a car accident 2 years before otolaryngologic attendance. He had one
      episode of generalized tonic-clonic seizure and developed a reduction of visual
      acuity of the left side after the accident. Neurologic investigation was
      performed and magnetic resonance imaging revealed an incidental finding of a
      heterogeneous ovoid lesion in the pterygopalatine fossa, hyperintense on T2
      weighted imaging. Results Endoscopic sinus surgery with transpterygoid approach
      was performed. The ovoid lesion was noted in the pterygopalatine fossa. Puncture
      for intraoperative evaluation showed a transparent thick fluid. Surprisingly,
      hair and sebaceous glands were found inside the cyst capsule. The cyst was
      excised completely. Histologic examination revealed a dermoid cyst. The patient
      currently has no evidence of recurrence at 1 year postoperatively. Conclusion
      This unique case is a rare report of a dermoid cyst incidentally diagnosed. An
      endoscopic transnasal transpterygoid approach may be performed to treat
      successfully this kind of lesion. Although rare, it should be considered in the
      differential diagnosis of expansive lesions in the pterygopalatine fossa,
      including schwannoma, angiofibroma, esthesioneuroblastoma, osteochondroma,
      cholesterol granuloma, hemangioma, lymphoma, and osteoma. 

PMID- 25992072
TI  - Dysphagia: a symptom to be controlled.

PMID- 25992071
TI  - Synovial sarcoma in head and neck: a case report.
AB  - Introduction Synovial sarcoma is a malignant tumor of mesenchymal pluripotent
      cells. Objectives We present a case of synovial sarcoma in the posterolateral
      wall of the oropharynx. Resumed report The patient, a 23-year-old woman, was
      admitted with a history of dysphagia and difficulty in breathing for 8 months,
      resulting in progressive deterioration and onset of snoring, muffled voice, and
      local pain. An oropharyngeal tumor in the left posterolateral wall touched the
      base of the ipsilateral tongue. The patient underwent endoscopic pharyngectomy to
      remove the lesion. Pathologic examination revealed synovial sarcoma with positive
      margins, and Mohs technique was proposed for margin control. The margins were
      disease-free, without the need for total laryngectomy. The pharynx was
      reconstructed with a microvascular forearm flap. The patient developed
      postoperative stability. Conclusion Despite its name, synovial sarcoma is rarely
      sourced directly from synovial membranes. It is most commonly found in the
      vicinity of large joints. The location at the head and neck, a location poor in
      synovial tissue, is unusual. Synovial sarcoma in the head and neck has an
      aggressive nature and poor prognosis. Resection with negative margins remains the
      foundation of therapy, which is not so easily achieved in the head and neck. It
      is important for the otorhinolaryngologist and head and neck surgeon to be
      familiar with this aggressive tumor, which carries high mortality and morbidity.
      The appropriate diagnosis and treatment can improve prognosis and patient
      survival. 

PMID- 25992073
TI  - Evaluating the effectiveness of the lateral intercrural suture to decrease the
      interdomal distance to improve the definition of the nasal tip in primary
      rhinoplasty.
AB  - Introduction Several surgical techniques emphasizing sutures on the lower lateral
      cartilage have been studied by surgeons as instruments to improve nasal tip
      remodeling. It is already known that the domal divergence angle and its
      definition angle can be modified by lateral intercrural suture (LIS). Techniques
      for measuring these structures are not yet standardized. Objectives Assess the
      efficacy of LIS using polydioxanone 4-0 absorbable thread by interdomal distance
      and systematize the LIS technique to improve nasal tip definition. Materials and
      Methods This prospective study measured and analyzed interdomal distances
      measured preoperatively and perioperatively compared with 3- and 6-month
      postoperative measurements. Results LIS was efficient on reducing interdomal
      distances. Conclusion LIS is statistically safe and efficient and has low
      morbidity when utilized in patients with mild to moderate deformities, because it
      reduces the domal divergence angle, effectively sustaining the nasal tip. 

PMID- 25992074
TI  - Tracheal decannulation protocol in patients affected by traumatic brain injury.
AB  - Introduction The frequency of tracheostomy in patients with traumatic brain
      injury (TBI) contrasts with the lack of objective criteria for its management.
      The study arose from the need for a protocol in the decision to remove the
      tracheal tube. Objective To evaluate the applicability of a protocol for tracheal
      decannulation. Methods A prospective study with 20 patients, ranging between 21
      and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men
      (80%). All patients had been diagnosed by a neurologist as having TBI, and the
      anatomical region of the lesion was known. Patients were evaluated following
      criteria for tracheal decannulation through a clinical evaluation protocol
      developed by the authors. Results Decannulation was performed in 12 (60%)
      patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and
      only 2 (14%) of these were not able to undergo decannulation. Twelve (60%)
      patients maintained the breathing pattern with occlusion of the tube and were
      successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs
      suggestive of tracheal aspiration, and of these, 9 (82%) began training on
      occlusion of the cannula. The protocol was relevant to establish the beginning of
      the decannulation process. The clinical assessment should focus on the patient's
      condition to achieve early tracheal decannulation. Conclusion This study allowed,
      with the protocol, to establish six criteria for tracheal decannulation: level of
      consciousness, respiration, tracheal secretion, phonation, swallowing, and
      coughing. 

PMID- 25992075
TI  - Elaboration and Evaluation of Contents about Hearing Health Inserted in
      Cybertutor.
AB  - Introduction Cybertutor (electronic tutor) is a type of information and
      communication technology to disseminate knowledge about hearing, aiming at the
      prevention of hearing alterations and, when needed, early treatment, in addition
      to social inclusion of the hearing impaired. However, it is important to evaluate
      the level of language used in the content and the subjective perception of the
      target public regarding improvements of the tool. Objective To improve content
      about hearing health inserted in a cybertutor and to evaluate the level of
      legibility and the quality of the content and material made available. Method For
      the construction of the content, text and audiovisual resources were used, based
      on scientific publications, and were evaluated objectively with Flesch Reading
      Ease test and subjectively with a questionnaire created by the authors and
      answered by 10 ninth-year pupils. Results Two modules on hearing health were
      created, "Hearing Health" and "Intervention and Rehabilitation," which received
      Flesch scores of 50.8 and 51.4%, respectively, making it necessary to have a
      sixth- to ninth-year education to understand the material. The students'
      evaluation in reference to language and material showed that 55.5% considered the
      contents excellent; 38.2% classified the contents as satisfactory; 6.3%
      considered them reasonable; and 0% classified them as unsatisfactory. Conclusion
      The contents inserted in the cybertutor about hearing health presented a language
      level considered easy for the age group of the target population, in addition to
      receiving good subjective evaluation from the pupils, facilitating access to the
      information. 

PMID- 25992076
TI  - Vestibular findings in military band musicians.
AB  - Introduction Exposure to music is the subject of many studies because it is
      related to an individual's professional and social activities. Objectives
      Evaluate the vestibular behavior in military band musicians. Methods A
      retrospective cross-sectional study was performed. Nineteen musicians with ages
      ranging from 21 to 46 years were evaluated (average = 33.7 years and standard
      deviation = 7.2 years). They underwent anamnesis and vestibular and
      otolaryngologic evaluation through vectoelectronystagmography. Results The most
      evident otoneurologic symptoms in the anamnesis were tinnitus (84.2%), hearing
      difficulties (47.3%), dizziness (36.8%), headache (26.3%), intolerance to intense
      sounds (21.0%), and earache (15.7%). Seven musicians (37.0%) showed vestibular
      abnormality, which occurred in the caloric test. The abnormality was more
      prevalent in the peripheral vestibular system, and there was a predominance of
      irritative peripheral vestibular disorders. Conclusion The alteration in
      vestibular exam occurred in the caloric test (37.0%). There were changes in the
      prevalence of peripheral vestibular system with a predominance of irritative
      vestibular dysfunction. Dizziness was the most significant symptom for the
      vestibular test in correlation with neurotologic symptoms. The present study made
      it possible to verify the importance of the labyrinthine test, which demonstrates
      that this population should be better studied because the systematic exposure to
      high sound pressure levels may cause major vestibular alterations. 

PMID- 25992077
TI  - Masticatory changes in oral breath secondary to allergic rhinitis: integrative
      review.
AB  - Introduction The III Brazilian Consensus on Rhinitis (2012) defines allergic
      rhinitis as a nasal mucosa inflammation, mediated by immunoglobulin E, after
      exposure to allergens. The classic signs and symptoms of allergic rhinitis are
      nasal obstruction, watery rhinorrhea, sneezing, and nasal itching, often
      reversible either spontaneously or with treatment, and mouth breathing (breathing
      predominantly through the mouth, regardless of the cause, due to a nasal
      breathing impairment) in some cases. Objective To evaluate the literature on
      masticatory changes in children with mouth breathing due to allergic rhinitis.
      Methods We conducted a search of the past 10 years, at Bireme and MEDLINE
      databases, for articles that covered masticatory changes in children with mouth
      breathing secondary to allergic rhinitis. Results We found 1,986 articles,
      including 15 repeated in databases, but only two articles met the inclusion
      criteria fully. Discussion We found few studies to answer the question raised in
      this review, and those studies have some methodological limitations. Most
      articles claimed no have statistically significant differences in masticatory
      changes in this population. Conclusion A better controlled study (isolating
      diseases, exposure time), with a larger sample (sample calculation appropriate),
      would be necessary to examine such changes. 

PMID- 25992078
TI  - The Role of Speech Therapy in Patients Who Underwent Laryngeal Microsurgery due
      to Phonotraumatic Lesions and Lesions Unrelated to Phonotrauma.
AB  - Introduction The role of the speech-language pathology in the multiprofessional
      team dealing with laryngology and the voice has been recognized for a long time.
      Scientific studies in this field recommend therapies for laryngeal
      microsurgeries; few of the studies, however, effectively evaluate the result of
      postoperative speech therapy. Objective To compare speech therapy evaluation and
      treatment among patients with phonotraumatic lesions and patients with lesions
      unrelated to phonotrauma who underwent laryngeal microsurgery. Methods This study
      was performed at IPO Hospital (Paranaense Institute of Otorhinolaryngology,
      Curitiba, Parana, Brazil) between February 2010 and February 2011. Of 254
      patients who underwent laryngeal microsurgery, 208 patients were included in the
      study and divided in two groups: group A with phonotraumatic lesions (n = 131)
      and group B with lesions unrelated to phonotrauma (n = 77). The number of
      sessions and the functional result after speech therapy were evaluated. Results
      The number of postoperative phonotherapy sessions after microsurgery was up to 10
      sessions in 89.31% and 87.71% for groups A and B, respectively. Phonotherapy
      treatment showed a better functional evolution in group A (92.37%). Conclusion A
      significant difference was observed only in functional evolution, which was
      better in the group with phonotraumatic lesions (p < 0.0001). 

PMID- 25992079
TI  - Auditory effects of exposure to noise and solvents: a comparative study.
AB  - Introduction Industry workers are exposed to different environmental risk agents
      that, when combined, may potentiate risks to hearing. Objective To evaluate the
      effects of the combined exposure to noise and solvents on hearing in workers.
      Methods A transversal retrospective cohort study was performed through
      documentary analysis of an industry. The sample (n = 198) was divided into four
      groups: the noise group (NG), exposed only to noise; the noise and solvents group
      (NSG), exposed to noise and solvents; the noise control group and noise and
      solvents control group (CNS), no exposure. Results The NG showed 16.66% of cases
      suggestive of bilateral noise-induced hearing loss and NSG showed 5.26%. The NG
      and NSG had worse thresholds than their respective control groups. Females were
      less susceptible to noise than males; however, when simultaneously exposed to
      solvents, hearing was affected in a similar way, resulting in significant
      differences (p < 0.05). The 40- to 49-year-old age group was significantly worse
      (p < 0.05) in the auditory thresholds in the NSG compared with the CNS.
      Conclusion The results observed in this study indicate that simultaneous exposure
      to noise and solvents can damage the peripheral auditory system. 

PMID- 25992080
TI  - Epidemiologic profile of patients with snoring and obstructive sleep apnea in a
      university hospital.
AB  - Introduction There are several studies on the pathophysiology and prevalence of
      Obstructive Sleep Apnea Syndrome (OSAS), however, few studies address the
      epidemiological profile of these patients. Objective The aim of this study is to
      analyze the epidemiological profile of patients diagnosed with OSAS referred to
      the Sleep Medicine clinic. Methods Cross-sectional individualized study covering
      57 patients who were referred from the general ENT clinic to the Sleep Medicine
      clinic. Results Classification of OSAS: 16% had primary snoring, 14% mild OSAS,
      18% moderate OSAS, and 52% severe OSAS. Distribution according to weight: 7% had
      normal weight, 2% were overweight (BMI 2530), 37% grade I obesity (BMI 25.1 to
      30); 9% grade II obesity (BMI 30.1 to 35) and grade III obesity (BMI greater than
      35) in 45% of cases. Distribution Friedmann stage: 9% were classified as grade I,
      35% were considered grade II, 54% as grade III and 2% as grade IV. Treatment
      adopted: 46% were treated with CPAP; 19% were treated with surgery; oral
      appliance was designed for 14% patients, 7% were given roncoplastic injection and
      7% positional therapy. A new polysomnography was asked to 5% of patients. To 2%
      of patients given the oral appliance was due to treatment failure with
      roncoplastic injection. Conclusion Most of the patients are male, obese and with
      moderate or severe OSAS. Snoring and daytime excessive sleepiness were the most
      common symptoms. The surgical procedures employed in this service (roncoplastic
      injection, UPPP and lateral pharyngoplasty) followed the recommendations of the
      available literature. 

PMID- 25992081
TI  - Temporal resolution ability in students with dyslexia and reading and writing
      disorders.
AB  - Introduction The Gaps-in-Noise (GIN) test assesses the hearing ability of
      temporal resolution. The development of this ability can be considered essential
      for learning how to read. Objective Identify temporal resolution in individuals
      diagnosed with reading and writing disorders compared with subjects with
      dyslexia. Methods A sample of 26 subjects of both genders, age 10 to 15 years,
      included 11 diagnosed with dyslexia and 15 diagnosed with reading and writing
      disorders. Subjects did not display otologic, neurologic, and/or cognitive
      diseases. A control group of 30 normal-hearing subjects was formed to compare
      thresholds and percentages obtained from the GIN test. The responses were
      obtained considering two measures of analysis: the threshold gap and the
      percentage of correct gap. Results The threshold was lower in the GIN for the
      typical group than for the other groups. There was no difference between groups
      with dyslexia and with reading and writing disorders. The GIN results of the
      typical group revealed a higher percentage of correct answer than in the other
      groups. No difference was obtained between the groups with dyslexia and with
      reading and writing disorders. Conclusion The GIN test identified a difficulty in
      auditory ability of temporal resolution in individuals with reading and writing
      disorders and in individuals with dyslexia in a similar way. 

PMID- 25992082
TI  - Detection of respiratory viruses in nasopharyngeal swab and adenoid tissue from
      children submitted to adenoidectomy: pre- and postoperative analysis.
AB  - Introduction The presence of respiratory viruses in lymphoid tissues of the
      nasopharynx and oropharynx and its impact on recurrent infections and hypertrophy
      of these tissues are not yet fully understood. Objective To identify and
      determine the prevalence of major respiratory viruses in nasopharyngeal
      secretions and adenoid tissue pre- and postoperatively of children undergoing
      adenoidectomy. Methods A prospective observational study was conducted in 36
      patients under 12 years of age with upper airway lymphoid hypertrophy who were
      undergoing adenoidectomy, in which various respiratory viruses were investigated
      using real-time polymerase chain reaction in adenoid tissue and nasopharyngeal
      secretions collected preoperatively and 30 days postoperatively. Results At least
      1 viral agent was isolated in any of the samples collected in 58.3% of children
      and 25.9% of total samples. Respiratory viruses were identified in 33.8% of
      preoperative nasopharyngeal specimens and in 19.8% of postoperative secretion. Of
      the 21 patients with positive results for any respiratory virus, 6 (28.6%) had
      more than 1 virus. Considering all 36 respiratory viruses found, the main agent
      isolated was rhinovirus (27.8%), followed by bocavirus (22.2%). Conclusion The
      virus found more frequently in all samples was rhinovirus. After removal of
      adenoid tissue, there was a decrease in the prevalence of the virus contained in
      nasopharyngeal secretion 30 days after surgery. 

PMID- 25992083
TI  - Reducing postoperative pain from tonsillectomy using monopolar electrocautery by
      cooling the oropharynx.
AB  - Objective Evaluate intraoperative cooling of the oropharynx to reduce
      postoperative pain in tonsillectomy using monopolar electrocautery. Methods Sixty
      six patients, age 1 to 12 years, were selected for the study, 33 in the control
      group and 33 in the experimental group. After randomization, patients underwent
      subcapsular dissection and hemostasis with monopolar electrocautery. Patients in
      the experimental group had the oropharynx cooled after tonsil dissection and
      hemostasis for 10 minutes. The procedure was done through the oral cavity by
      irrigation with 500 mL of 0.9% saline, in temperatures between 5 degrees C and 10
      degrees C, for 5 minutes. The evaluation of postoperative pain was made with the
      pain visual analog scale (VAS) for 10 days. As complementary data on the
      evaluation of pain, we recorded daily use of ketoprofen for pain relief. Results
      Pain after tonsillectomy assessed by VAS was significantly lower in the
      experimental group at days 0, 5, and 6 (p < 0.05). There were no differences in
      the use of ketoprofen between the groups. Conclusion Cooling of the oropharynx
      after tonsillectomy promotes clinically significant reduction in postoperative
      pain, without additional complications. 

PMID- 25992084
TI  - Role of modified endoscopic medial maxillectomy in persistent chronic maxillary
      sinusitis.
AB  - Introduction Functional endoscopic sinus surgery has a long-term high rate of
      success for symptomatic improvement in patients with medically refractory chronic
      rhinosinusitis. As the popularity of the technique continues to grow, however, so
      does the population of patients with postsurgical persistent sinus disease,
      especially in those with a large window for ventilation and drainage. In
      addition, chronic infections of the sinuses especially fungal sinusitis have a
      higher incidence of recurrence even though a wide maxillary ostium had been
      performed earlier. This subset of patients often represents a challenge to the
      otorhinolaryngologist. Objectives To identify the patients with chronic
      recalcitrant maxillary sinusitis and devise treatment protocols for this subset
      of patients. Methods A retrospective review was done of all patients with
      persistent maxillary sinus disease who had undergone modified endoscopic medial
      maxillectomy between 2009 and 2012. We studied patient demographics, previous
      surgical history, and follow-up details and categorized the types of endoscopic
      medial maxillectomies performed in different disease situations. Results We
      performed modified endoscopic medial maxillectomies in 37 maxillary sinuses of 24
      patients. The average age was 43.83 years. Average follow-up was 14.58 months.
      All patients had good disease control in postoperative visits with no clinical
      evidence of recurrences. Conclusion Modified endoscopic medial maxillectomy
      appears to be an effective surgery for treatment of chronic, recalcitrant
      maxillary sinusitis. 

PMID- 25992085
TI  - The Audiometric Findings among Curitiba and Metropolitan Area Students.
AB  - Introduction Hearing loss can compromise the language, learning process, and
      socialization of students. Objective Study the audiometric findings among
      Curitiba and Metropolitan Area students. Methods Analysis of data collected at
      the hearing health service of Parana State special education and inclusion
      department. Results The sample consisted of 646 students, children and teenagers
      of both genders (38.2% female and 61.8% male), with average age of 8.12 years
      (range 2 to 15); all were students of public or private schools of Curitiba and
      Metropolitan Area. The justifications to refer the students to audiometric
      evaluation were: otolaryngologists diagnosis (73.1%), school difficulties
      (39.6%), and midlevel hearing problems (32%). Audiometric results showed that
      29.5% of the students had hearing loss. Conductive hearing losses showed the
      greatest occurrence among preschool students (right ear 38.6%, left ear 39.8%).
      The predominant hearing loss degree was mild (RE 20.5%, LE 19.3%) to slight (RE
      17%, LE 19.3%), as was the horizontal configuration (RE 81.5%, LE 78.4%). A
      significant relationship (p = 0.0000) between hearing loss and poor school
      performance was noted. Conclusion Considering the available data, especially the
      high number of findings of conductive losses, it is necessary to highlight
      prevention and diagnosis of early hearing alteration. Nevertheless, Brazil, as an
      emerging country, has been pursuing improvement in health and life quality of all
      citizens. 

PMID- 25992086
TI  - Analysis of the level of Dysphagia, anxiety, and nutritional status before and
      after speech therapy in patients with stroke.
AB  - INTRODUCTION:  The rehabilitation in oropharyngeal dysphagia evidence-based
      implies the relationship between the interventions and their results. OBJECTIVE: 
      Analyze level of dysphagia, oral ingestion, anxiety levels and nutritional status
      of patients with stroke diagnosis, before and after speech therapy. METHOD: 
      Clinical assessment of dysphagia partially using the Protocol of Risk Assessment
      for Dysphagia (PARD), applying the scale Functional Oral Intake Scale for
      Dysphagia in Stroke Patients (FOIS), Beck Anxiety Inventory (BAI) and the Mini
      Nutritional Assessment MNA((r)). The sample consisted of 12 patients, mean age of
      64.6 years, with a medical diagnosis of hemorrhagic and ischemic stroke and
      without cognitive disorders. All tests were applied before and after speech
      therapy (15 sessions). Statistical analysis was performed using the chi-square
      test or Fisher's exact test, McNemar's test, Bowker's symmetry test and
      Wilcoxon's test. RESULTS:  During the pre-speech therapy assessments, 33.3% of
      patients had mild to moderate dysphagia, 88.2% did not receive food orally, 47.1%
      of the patients showed malnutrition and 35.3% of patients had mild anxiety level.
      After the therapy sessions, it was found that 33.3% of patients had mild
      dysphagia, 16.7% were malnourished and 50% of patients had minimal level of
      anxiety. CONCLUSION:   There were statistically significant evolution of the
      level of dysphagia (p = 0.017) and oral intake (p = 0.003) post-speech therapy.
      Although not statistically significant, there was considerable progress in
      relation to the level of anxiety and nutritional status.

PMID- 25992087
TI  - Epidemiology of intratemporal complications of otitis media.
AB  - Introduction Despite the advent of antibiotics and immunizations in the last
      century, complications of otitis media remain quite frequent, have high morbidity
      and mortality rates, and pose a challenge to the otorhinolaryngologist. Objective
      To establish the annual incidence of intratemporal complications of otitis media
      and prospectively evaluate patients via an analysis of epidemiologic and clinical
      aspects. Methods Prospective, observational study. Between February 2010 and
      January 2011, patients admitted to a tertiary care, university-based otology
      practice with diagnosis of otitis media and an associated intratemporal
      complication (ITC) were included in the study. The following data were evaluated:
      age, sex, type of ITC, treatment, imaging tests findings, type and degree of
      hearing loss, and clinical outcome. The overall incidence of all complications
      and of each complication individually was determined. Results A total of 1,816
      patients were diagnosed with otitis media. For 592 (33%) individuals, the
      diagnosis was chronic otitis media; for 1,224 (67%), the diagnosis was acute
      otitis media. ITCs of otitis media were diagnosed in 15 patients; thus, the
      annual incidence of intratemporal complications was 0.8%. We identified 19 ITC
      diagnoses in 15 patients (3 patients had more than one diagnosis). Labyrinthine
      fistulae were diagnosed in 7 (36.8%) individuals, mastoiditis in 5 (26.3%),
      facial palsy in 4 (21.1%), and labyrinthitis in 3 (15.8%). Conclusion The
      incidence of intratemporal complications in Brazil remains significant when
      compared with developed countries. Chronic otitis media with cholesteatoma is the
      most frequent etiology of intratemporal complications. Labyrinthine fistula is
      the most common intratemporal complication. 

PMID- 25992088
TI  - Laryngopharyngeal reflux: diagnosis, treatment, and latest research.
AB  - Introduction Laryngopharyngeal reflux (LPR) is a highly prevalent disease and
      commonly encountered in the otolaryngologist's office. Objective To review the
      literature on the diagnosis and treatment of LPR. Data Synthesis LPR is
      associated with symptoms of laryngeal irritation such as throat clearing,
      coughing, and hoarseness. The main diagnostic methods currently used are
      laryngoscopy and pH monitoring. The most common laryngoscopic signs are redness
      and swelling of the throat. However, these findings are not specific of LPR and
      may be related to other causes or can even be found in healthy individuals.
      Furthermore, the role of pH monitoring in the diagnosis of LPR is controversial.
      A therapeutic trial with proton pump inhibitors (PPIs) has been suggested to be
      cost-effective and useful for the diagnosis of LPR. However, the recommendations
      of PPI therapy for patients with a suspicion of LPR are based on the results of
      uncontrolled studies, and high placebo response rates suggest a much more complex
      and multifactorial pathophysiology of LPR than simple acid reflux. Molecular
      studies have tried to identify biomarkers of reflux such as interleukins,
      carbonic anhydrase, E-cadherin, and mucin. Conclusion Laryngoscopy and pH
      monitoring have failed as reliable tests for the diagnosis of LPR. Empirical
      therapy with PPIs is widely accepted as a diagnostic test and for the treatment
      of LPR. However, further research is needed to develop a definitive diagnostic
      test for LPR. 

PMID- 25992089
TI  - Nostril Morphometry Evaluation before and after Cleft Lip Surgical Correction:
      Clinical Evidence.
AB  - Introduction The purpose to this work is to review systematically the
      morphological changes of the nostrils of patients undergoing surgery for
      correction of cleft lip and identify in the literature the issues involved in the
      evaluation of surgical results in this population. Review of Literature A review
      was conducted, searching for clinical evidence from MEDLINE. The search occurred
      in January 2012. Selection criteria included original articles and research
      articles on individual subjects with cleft lip or cleft palate with unilateral
      nostril anthropometric measurements before and after surgical correction of cleft
      lip and measurements of soft tissues. There were 1,343 articles from the search
      descriptors and free terms. Of these, five articles were selected. Discussion
      Most studies in this review evaluated children in Eastern countries, using
      different measurement techniques but with the aid of computers, and showed
      improved nostril asymmetry postoperatively compared with preoperatively.
      Conclusion There is a reduction of the total nasal width postoperatively compared
      with preoperative measurements in patients with cleft lip. 

PMID- 25992090
TI  - Language disorders in children with unilateral hearing loss: a systematic review.
AB  - Introduction Childhood is a critical period for language development and
      maturation of the central auditory system. Unilateral hearing loss (UHL) is
      considered a minimal impairment, and little is discussed regarding its impact on
      the development of language, communication, and school performance. Objectives A
      bibliographical survey of scientific articles published from 2001 to 2011 was
      performed to verify which language disorders can occur in children with UHL and
      which tests were performed to identify them. Data Synthesis Three databases were
      used: PubMed, Lilacs, and The Cochrane Library. As inclusion criteria, the
      articles should have samples of children with UHL, without other impairments,
      aged between 3 months and 12 years, and reference to language tests applied in
      this population. Out of 236 papers initially selected, only 5 met the inclusion
      criteria. In the articles studied, 12 tests were used for language assessment in
      children with UHL, out of which 9 were directed toward expressive language, and 3
      toward receptive language. Children with UHL demonstrated lower scores on
      receptive and expressive language tests when compared with children with normal
      hearing. However, they obtained better scores on expressive language tests than
      children with bilateral hearing loss. Conclusion The findings of this survey
      showed that only a small number of studies used language tests in children with
      UHL or addressed language alterations resulting from this type of impairment.
      Therefore we emphasize the importance of investments in new studies on this
      subject to provide better explanations related to language difficulties presented
      by children with UHL. 

PMID- 25992091
TI  - Update on middle ear barotrauma after hyperbaric oxygen therapy-insights on
      pathophysiology.
AB  - Introduction Middle ear barotrauma is the most common side effect of hyperbaric
      oxygen therapy. Knowledge and understanding of its pathophysiology are crucial
      for an accurate diagnosis and proper decision making about treatment and
      prevention. Objective Describe up-to-date information on pathophysiology of
      middle ear barotrauma after hyperbaric oxygen therapy considering the physiology
      of pressure variation of the middle ear. Data Synthesis Middle ear barotrauma
      occurs especially during the compression phase of hyperbaric oxygen therapy. The
      hyperoxic environment in hyperbaric oxygen therapy leads to ventilatory
      dysfunction of the eustachian tube, especially in monoplace chambers, where the
      patients are pressurized with 100% O2, favoring middle ear barotrauma. Conclusion
      The eustachian tube, the tympanic cavity, and mastoid work together in a neural
      controlled feedback system in which various mechanisms concur for middle ear
      pressure regulation. 

PMID- 25992092
TI  - Superior Semicircular Canal Dehiscence Syndrome without Vestibular Symptoms.
AB  - Introduction Superior semicircular canal dehiscence syndrome is mainly
      characterized by vestibular symptoms induced by intense sound stimuli or pressure
      changes, which occur because of dehiscence of the bony layer covering the
      superior semicircular canal. Case Report Here, we report a case of the syndrome
      with pulsatile tinnitus and ear fullness, in the absence of vestibular symptoms.
      Discussion Signs and symptoms of the syndrome are rarely obvious, leading to the
      requirement for a minimum workup to rule out or make diagnosis more probable and
      thus avoid misconduct. 

PMID- 25992093
TI  - Subcutaneous cavernous hemangioma in the nasal dorsum: report of case treated
      with endoscopic rhinoplasty.
AB  - Introduction Hemangiomas are vascular malformations, with slow blood flow, that
      can occur in any part on the body. They are more common in women and,
      predominantly, are isolated lesions. The malformation does not spontaneously
      regress. Subcutaneous hemangioma is a rare variant with an aggressive growth
      pattern that sometimes recurs after excision. Objective Case report of a
      subcutaneous cavernous hemangioma in the nasal dorsum treated with endoscopic
      rhinoplasty. Case Report A 27-year-old woman had a fibroelastic tumor mass in the
      midline of the nasal dorsum, which was pulsatile; she had obstruction and nasal
      congestion with associated rhinorrhea, with evolution and worsening over the
      previous 2 years. Computed tomography showed a tumor demarcated in the nasal
      dorsum without evidence of intracranial communication. Endoscopic rhinoplasty
      with septoplasty and associated paranasal sinus sinusectomy was performed without
      arteriography embolization, sclerotherapy, or laser. Pathologic diagnosis showed
      cavernous hemangioma. Postoperative follow-up shows no recurrence at 3 years.
      Discussion This case presented with atypical features, thus making the diagnosis
      a challenge. Imaging studies were required to confirm the vascular nature of the
      tumor. Excisional biopsy is the procedure of choice for pathologic examination.
      Subcutaneous hemangiomas never involute and always need treatment. The surgical
      approach is exceptional because there was no preoperative diagnosis. In addition,
      the closed technique provided best aesthetic results in this case. Conclusion
      Endoscopic rhinoplasty is suitable for nasal dorsum tumor resection and has
      superior aesthetic result to open techniques. 

PMID- 25992094
TI  - Synchronous bilateral warthin tumors: a case report.
AB  - Introduction Warthin tumor is described as papillary cystadenoma lymphomatosum
      and is the second most common tumor of the parotid glands. Bilateral synchronous
      incidence is rare, occurring in 7 to 10% of the cases. It is more common in males
      between 60 and 70 years of age and is closely related to smoking. There is slow
      growth and the condition is a delimited nodule of regular outlines; it has low
      rates of malignant progression and recurrence. Objective Report a case of
      synchronous bilateral Warthin tumor occurring in an elderly patient, and review
      incidence and peculiarities of this tumor. Case Report A 78-year-old man who used
      to smoke had a history of mild pain in the topography of right parotid three
      weeks ago. Patient with hypertension, diabetes and a longtime smoker (smoking a
      pack per day for 32 years) noticed a progressive bulging in the right parotid
      region for about 2.5 years ago, and noticed another progressive bulging
      (althought in the left parotid region), for about one year ago. Patient denied
      fever, redness, skin lesions and pain during this period until last three weeks,
      when he sought medical attention for a mild pain in the right facial region. The
      patient underwent cervical magnetic resonance imaging that showed tumor lesions
      in both parotids. Fine needle aspiration revealed a typical lesion of epithelial
      oxyphilic cells associated with reactive lymphoid proliferation, suggesting
      Warthin tumor. The patient underwent two superficial parotidectomies, and the
      histopathologic result from both tumors of parotid glands showed papillary
      cystadenoma lymphomatosum. Conclusion The occurrence of synchronous bilateral
      Warthin tumor is extremely rare, and anamnesis and physical examination, as well
      as some complementary examinations, are important means for diagnostic
      evaluation. Confirmation of the diagnosis can only be obtained through a
      histopathologic study. A superficial or total parotidectomy is the recommended
      treatment for the disease. 

PMID- 25992095
TI  - Adenoid cystic carcinoma mimicking an oroantral fistula: a case report.
AB  - Introduction Adenoid cystic carcinoma (ACC) is one of the most frequent malignant
      salivary gland tumors, which commonly affects the minor salivary glands of the
      mouth and is rare in the nose and paranasal sinuses. In the maxillary sinus, ACC
      can mimic inflammatory diseases and has a poor prognosis. Objective To report a
      case of a 50-year-old man with ACC of the maxillary sinus whose clinical findings
      in the alveolar ridge mimicked an oroantral fistula. Case Report An excisional
      biopsy was performed and histopathologic analysis revealed ACC. Lung metastases
      and residual tumor in the maxillary sinus were detected by imaging methods. In
      view of the poor general health of the patient, no new surgical intervention was
      performed and he was only treated by radiotherapy and follow-up. Conclusion
      Although rare in the maxillary sinus, ACC should be included in the differential
      diagnosis of lesions affecting this site. 

PMID- 25992096
TI  - The etiology of mobius syndrome: a social problem?

PMID- 25992097
TI  - Level of user satisfaction with hearing AIDS and environment: the international
      outcome inventory for hearing AIDS.
AB  - Introduction The main function of hearing is to enable oral communication.
      Hearing loss impairs communication skills. Objective To evaluate the level of
      user satisfaction with hearing aids. Methods This is a cross-sectional group
      study comprising 108 subjects (56% men and 44% women). The average age of the
      subjects was 77 years. These subjects had been recently fitted with their hearing
      aids and showed sensorineural (90%) and mixed (10%) hearing loss as determined
      via the Questionnaire International Outcome Inventory for Hearing Aids Outcome
      Inventory (IOI-HA), which determined the benefit and satisfaction obtained by
      sound amplification. Results The hearing aids improved the quality of life of
      52.78% of the patients, which was revealed by their high scores (mean = 27.3).
      The relationship of the user with the environment was significantly better (p <
      0.001) than that of the user with the hearing aid. Conclusion IOI-HA is a simple
      and easy-to-use tool. Based on the results of this study, we can show a high
      degree of satisfaction with their hearing aids in the majority of the
      participants, which improved the quality of life. 

PMID- 25992098
TI  - Central vestibular dysfunction in an otorhinolaryngological vestibular unit:
      incidence and diagnostic strategy.
AB  - Introduction Vertigo can be due to a variety of central and peripheral causes.
      The relative incidence of central causes is underestimated. This may have an
      important impact of the patients' management and prognosis. Objective The
      objective of this work is to determine the incidence of central vestibular
      disorders in patients presenting to a vestibular unit in a tertiary referral
      academic center. It also aims at determining the best strategy to increase the
      diagnostic yield of the patients' visit. Methods This is a prospective
      observational study on 100 consecutive patients with symptoms suggestive of
      vestibular dysfunction. All patients completed a structured questionnaire and
      received bedside and vestibular examination and neuroimaging as required. Results
      There were 69 women and 31 men. Their ages ranged between 28 and 73 (mean 42.48
      years). Provisional videonystagmography (VNG) results were: 40% benign paroxysmal
      positional vertigo (BPPV), 23% suspicious of central causes, 18% undiagnosed, 15%
      Meniere disease, and 4% vestibular neuronitis. Patients with an unclear diagnosis
      or central features (41) had magnetic resonance imaging (MRI) and Doppler
      studies. Combining data from history, VNG, and imaging studies, 23 patients (23%)
      were diagnosed as having a central vestibular lesion (10 with generalized
      ischemia/vertebra basilar insufficiency, 4 with multiple sclerosis, 4 with
      migraine vestibulopathy, 4 with phobic postural vertigo, and 1 with
      hyperventilation-induced nystagmus). Conclusions Combining a careful history with
      clinical examination, VNG, MRI, and Doppler studies decreases the number of
      undiagnosed cases and increases the detection of possible central lesions. 

PMID- 25992099
TI  - Mobius syndrome: misoprostol use and speech and language characteristics.
AB  - Introduction Mobius syndrome (MS; VI and VII palsy) is a rare disease that in
      Brazil has a great frequency because of the use of misoprostol during pregnancy.
      Objective Verify if the speech and language performance of children with MS whose
      mothers reported use of misoprostol (Cytotec, Pfizer, Connecticut, USA) are
      different from the performance of children of mothers who did not report use.
      Methods The stomatognathic system beyond receptive and expressive language and
      speech was evaluated in children with MS, and their mothers were questioned
      whether they used misoprostol during the pregnancy. Results During the interview,
      61.11% of mothers reported that they took misoprostol during the pregnancy. Most
      of the subjects (83.3%) whose mothers took misoprostol presented bilateral palsy
      beyond bad mobility of the tongue (90.9%) and speech disorders (63.6%).
      Conclusion The number of mothers who took misoprostol without knowing the risk
      for MS was great. The lack of facial expressions and speech disorders were common
      characteristics of the individuals with MS, whether the mothers took misoprostol
      during the pregnancy or not. 

PMID- 25992100
TI  - Program to diagnose probability of aspiration pneumonia in patients with ischemic
      stroke.
AB  - Introduction Stroke is a major cause of death and disability worldwide, with a
      strong economic and social impact. Approximately 40% of patients show motor,
      language, and swallowing disorders after stroke. Objective To evaluate the use of
      software to infer the probability of pneumonia in patients with ischemic stroke.
      Methods Prospective and cross-sectional study conducted in a university hospital
      from March 2010 to August 2012. After confirmation of ischemic stroke by computed
      axial tomography, a clinical and flexible endoscopic evaluation of swallowing was
      performed within 72 hours of onset of symptoms. All patients received speech
      therapy poststroke, and the data were subsequently analyzed by the software. The
      patients were given medical treatment and speech therapy for 3 months. Results
      The study examined 52 patients with a mean age of 62.05 +/- 13.88 years, with 23
      (44.2%) women. Of the 52 patients, only 3 (5.7%) had a probability of pneumonia
      between 80 and 100% as identified by the software. Of all patients, 32 (61.7%)
      had pneumonia probability between 0 and 19%, 5 (9.5%) between 20 and 49%, 3
      (5.8%) between 50 and 79%, and 12 (23.0%) between 80 and 100%. Conclusion The
      computer program indicates the probability of patient having aspiration pneumonia
      after ischemic stroke. 

PMID- 25992101
TI  - Use of hearing AIDS and functional capacity in middle-aged and elderly
      individuals.
AB  - Introduction Hearing loss is among the sensory changes strongly associated with
      loss of functional capacity. Objective It aims to determine whether the use of
      hearing aid contributes to the improvement of instrumental activities of daily
      living (IADL) for middle aged and elderly hearing-impaired individuals. Methods
      This is a descriptive, longitudinal, and interventional study. We evaluated 17
      subjects, 13 (76.5%) female, aged between 58 and 96 years old (mean 77.1 +/- 10.4
      years). All were new users of hearing aids. Evaluation included social history,
      pure tone audiometry, and scale of IADL developed by Lawton and Brody. The
      subjects were presented daily life situations and were expected to respond if
      they could do them without assistance (3 points), partially assisted (2 points)
      or if they were unable to perform them (1 point). IADL was applied before the use
      of hearing aids adaptation and after a three- and six-month period of use.
      Results Data analysis revealed that before the use of hearing aids the average
      score obtained by the subjects was 22.94 +/- 4.04 points. Three months after
      beginning the use the average score was 23.29 +/- 4.12 and after six months the
      average score was 23.71 +/- 3.69 points. Statistical analysis revealed a
      significant difference between scores obtained before the use of hearing aids and
      six months post-fitting (p = 0.015*) Conclusion The use of hearing aids among the
      subjects evaluated promoted positive changes in performing IADL, especially to
      using the telephone. 

PMID- 25992102
TI  - Language in children with neonatal hypoxic-ischemic encephalopathy.
AB  - Introduction Neonatal hypoxic-ischemic encephalopathy (NHIE) is a common
      neurologic injury, and it may compromise the child's language and cognition.
      Understanding the process of language acquisition becomes possible with concise
      knowledge about children's global development. Objective The aim of this study
      was to observe if language acquisition and development are impaired in children
      with NHIE. Methods Seventy children with NHIE from 1 to 24 months old were
      analyzed in a Pediatric Neurology Service of Hospital of Porto Alegre, South of
      Brazil using the Brunet-Lezine Scale. Statistical analysis used SPSS 13.0
      software. Results Twenty-four (60%) of the subjects were boys, with mean
      gestational age of 35.8 weeks (standard deviation of 4.6) and mean Apgar score of
      6.0 at 1 minute and 7.1 at 5 minutes. The variables age versus language showed
      significant inverse correlation (r =  - 0.566; p = 0.028). As the subjects aged,
      language tasks became more specific and dependent on the subject's direct action,
      rather than the subjective interpretation of their guardian. This correlation
      seems to be closely associated with scale configuration and with consequences of
      neurologic disorder, evincing the delays in language development. Conclusion This
      study achieved the goals proposed and highlights the necessity of greater
      attention by professionals to language skills during the initial period of child
      development. 

PMID- 25992103
TI  - Primary extranodal non-hodgkin lymphoma of the head and neck in patients with
      acquired immunodeficiency syndrome: a clinicopathologic study of 24 patients in a
      single hospital of infectious diseases in Argentina.
AB  - Introduction Extranodal non-Hodgkin lymphomas (NHLs) are commonly described in
      patients with acquired immunodeficiency syndrome (AIDS) and are related with an
      atypical morphology and aggressive clinical course. AIDS-associated lymphomas are
      characterized by their rapid progression, frequent extranodal manifestations, and
      poor outcome. Objective The aim of this article is to remake the clinical
      features of head and neck (HN) NHL in patients with AIDS to facilitate early
      diagnosis and treatment. Methods We evaluated the epidemiologic, clinical,
      immunologic, virologic, and histopathologic characteristics of 24 patients with
      human immunodeficiency virus (HIV)/AIDS with primary HN NHL treated at a single
      institution between 2002 and 2012. Histopathologic diagnosis was made according
      to the criteria of the World Health Organization Classification of Tumors of
      Hematopoietic and Lymphoid Tissues. Additional immunohistochemical stains were
      applied in all cases. Results Eighteen patients (75%) were men and the median of
      age was 39 years. The gingiva and the hard palate were the most common sites of
      the lesions (15 patients, 62.5%). Lactate dehydrogenase levels were elevated in
      16 cases (84%). Bone marrow infiltration was detected only in 4 cases (16.6%).
      The median CD4 T-cell count was 100 cells/uL. According to the histopathologic
      evaluation, the most common subtype was diffuse large B-cell lymphoma (12 cases,
      50%), followed by plasmablastic lymphoma (9 cases, 37.5%) and Burkitt lymphoma (3
      cases, 12.5%). Conclusion HN NHL is a severe complication of advanced HIV/AIDS
      disease. Early diagnosis followed by chemotherapy plus highly active
      antiretroviral treatment is necessary to improve the prognosis and the survival
      of these patients. 

PMID- 25992104
TI  - Applicability and Effectiveness of Closed Reduction of Nasal Fractures under
      Local Anesthesia.
AB  - Introduction A significant portion of patients treated in emergency departments
      have nasal fracture. It is important that the otolaryngologist know how to treat
      such damage. Objectives To evaluate the effectiveness of nasal fracture reduction
      under local anesthesia and tolerance to the procedure. Methods Twenty-four
      patients treated in the emergency department with closed reduction under local
      anesthesia were prospectively followed. Epidemiologic information and data
      regarding pain and complications during the management were noted. The degree of
      satisfaction was researched by visual analog scale. Results The majority of
      patients were male (75%), and the most common cause of injury was motor vehicle
      accident. We found a significant association between time to reduction and
      referred pain during the procedure. In patients in whom the procedure was delayed
      (over 3 days), there was less pain, and those who bled during the procedure had a
      shorter average time to reduction than the group of patients who did not bleed.
      Most patients were very satisfied, with more than 95% of these willing to undergo
      the same process again, if necessary. Conclusions The closed approach in the
      clinic under local anesthesia was effective and safe in restoration of the nose. 

PMID- 25992105
TI  - Maximum bite force analysis in different age groups.
AB  - Introduction Maximum bite force (MBF) is the maximum force performed by the
      subject on the fragmentation of food, directly related with the mastication and
      determined by many factors. Objective Analyze the MBF of subjects according to
      age groups. Methods One hundred individuals from the city of Sao Paulo were
      equally divided according to age groups and gender. Each individual submitted to
      a myotherapy evaluation composed of anthropometric measurements of height and
      weight to obtain body mass index (BMI), using a tape and a digital scale (Magna,
      G-life, Sao Paulo), and a dental condition and maximum bite force evaluation,
      using a digital dynamometer model DDK/M (Kratos, Sao Paulo, Brazil), on Newton
      scale. The dental and bite force evaluations were monitored by a professional
      from the area. Analysis of variance was used with MBF as a dependent variable,
      age group and gender as random factors, and BMI as a control variable. Results
      Till the end of adolescence, it was possible to observe a decrease in MBF in both
      sexes, with the male force greater than the female force. In young adults, the
      female force became greater the males, then decreased in adulthood. There was no
      correlation between MBF and BMI. Conclusion There are MBF variations that
      characterizes the human development stages, according to age groups. 

PMID- 25992106
TI  - Mandibular branch of the facial nerve in wistar rats: new experimental model to
      assess facial nerve regeneration.
AB  - Introduction The ideal animal model for nerve regeneration studies is the object
      of controversy, because all models described by the literature have advantages
      and disadvantages. Objective To describe the histologic and functional patterns
      of the mandibular branch of the facial nerve of Wistar rats to create a new
      experimental model of facial nerve regeneration. Methods Forty-two male rats were
      submitted to a nerve conduction test of the mandibular branch to obtain the
      compound muscle action potential. Twelve of these rats had the mandibular branch
      surgically removed and submitted to histologic analysis (number, partial density,
      and axonal diameter) of the proximal and distal segments. Results There was no
      statistically significant difference in the functional and histologic variables
      studied. Conclusion These new histologic and functional standards of the
      mandibular branch of the facial nerve of rats establish an objective, easy, and
      greatly reproducible model for future facial nerve regeneration studies. 

PMID- 25992107
TI  - Treatment model in children with speech disorders and its therapeutic efficiency.
AB  - Introduction Speech articulation disorders affect the intelligibility of speech.
      Studies on therapeutic models show the effectiveness of the communication
      treatment. Objective To analyze the progress achieved by treatment with the ABAB
      Withdrawal and Multiple Probes Model in children with different degrees of
      phonological disorders. Methods The diagnosis of speech articulation disorder was
      determined by speech and hearing evaluation and complementary tests. The subjects
      of this research were eight children, with the average age of 5:5. The children
      were distributed into four groups according to the degrees of the phonological
      disorders, based on the percentage of correct consonants, as follows: severe,
      moderate to severe, mild to moderate, and mild. The phonological treatment
      applied was the ABAB-Withdrawal and Multiple Probes Model. The development of the
      therapy by generalization was observed through the comparison between the two
      analyses: contrastive and distinctive features at the moment of evaluation and
      reevaluation. Results The following types of generalization were found: to the
      items not used in the treatment (other words), to another position in the word,
      within a sound class, to other classes of sounds, and to another syllable
      structure. Conclusion The different types of generalization studied showed the
      expansion of production and proper use of therapy-trained targets in other
      contexts or untrained environments. Therefore, the analysis of the
      generalizations proved to be an important criterion to measure the therapeutic
      efficacy. 

PMID- 25992108
TI  - Evaluation of respiratory muscle strength in mouth breathers: clinical evidences.
AB  - Introduction The child who chronically breathes through the mouth may develop a
      weakness of the respiratory muscles. Researchers and clinical are seeking for
      methods of instrumental evaluation to gather complementary data to clinical
      evaluations. With this in mind, it is important to evaluate breathing muscles in
      the child with Mouth Breathing. Objective To develop a review to investigate
      studies that used evaluation methods of respiratory muscle strength in mouth
      breathers. Data Synthesis  The authors were unanimous in relation to
      manovacuometry method as a way to evaluate respiratory pressures in Mouth
      Breathing children. Two of them performed with an analog manovacuometer and the
      other one, digital. The studies were not evaluated with regard to the method
      efficacy neither the used instruments. Conclusion There are few studies
      evaluating respiratory muscle strength in Mouth Breathing people through
      manovacuometry and the low methodological rigor of the analyzed studies hindered
      a reliable result to support or refuse the use of this technique. 

PMID- 25992110
TI  - Implantable and semi-implantable hearing AIDS: a review of history, indications,
      and surgery.
AB  - Introduction The complaints associated with the use of conventional amplifying
      hearing aids prompted research at several centers worldwide that ultimately led
      to the development of implantable devices for aural rehabilitation. Objectives To
      review the history, indications, and surgical aspects of the implantable middle
      ear hearing devices. Data Synthesis Implantable hearing aids, such as the Vibrant
      Soundbridge system (Med-El Corporation, Innsbruck, Austria), the Maxum system
      (Ototronix LLC, Houston, Texas, United States), the fourth-generation of Carina
      prosthesis (Otologics LLC, Boulder, Colorado, United States), and the Esteem
      device (Envoy Medical Corporation - Minnesota, United States), have their own
      peculiarities on candidacy and surgical procedure. Conclusion Implantable hearing
      aids, which are currently in the early stages of development, will unquestionably
      be the major drivers of advancement in otologic practice in the 21st century,
      improving the quality of life of an increasingly aged population, which will
      consequently require increased levels of hearing support. 

PMID- 25992109
TI  - Improvement of vocal pathologies diagnosis using high-speed videolaryngoscopy.
AB  - Introduction The study of the dynamic properties of vocal fold vibration is
      important for understanding the vocal production mechanism and the impact of
      organic and functional changes. The advent of high-speed videolaryngoscopy (HSV)
      has provided the possibility of seeing the real cycle of vocal fold vibration in
      detail through high sampling rate of successive frames and adequate spatial
      resolution. Objective To describe the technique, advantages, and limitations of
      using HSV and digital videokymography in the diagnosis of vocal pathologies.
      Methods We used HSV and digital videokymography to evaluate one normophonic
      individual and four patients with vocal fold pathologies (nodules, unilateral
      paralysis of the left vocal fold, intracordal cyst, and adductor spasmodic
      dysphonia). The vocal fold vibration parameters (glottic closure, vibrational
      symmetry, periodicity, mucosal wave, amplitude, and glottal cycle phases) were
      assessed. Results Differences in the vocal vibration parameters were observed and
      correlated with the pathophysiology. Conclusion HSV is the latest diagnostic tool
      in visual examination of vocal behavior and has considerable potential to refine
      our knowledge regarding the vocal fold vibration and voice production, as well as
      regarding the impact of pathologic conditions have on the mechanism of phonation.

PMID- 25992111
TI  - Prevalence of microorganisms and immunoglobulins in children with tonsillar
      hypertrophy and adenoiditis.
AB  - INTRODUCTION:  Benign idiopathic tonsillar hypertrophy (HBI) may affect a child's
      quality of life and sleep. Several studies have sought to relate the clinical
      features of HBI with the infectious and/or immunologic changes that occur.
      OBJECTIVE:  To increase the knowledge of the etiology of HBI. DATA SYNTHESIS: 
      From 2012 to 2013 we conducted a retrospective observational study of 101
      children with HBI who underwent tonsillectomies at Ambulatory ENT General
      Hospital of the East Zone of Sao Paulo City, a region with a poor socioeconomic
      population. Preoperative serologic results were available to confirm
      mononucleosis, cytomegalovirus, anti-streptolysin O (ASLO) and immunoglobulins.
      The mean patient age was 5.8 years (55% male, 45% female). Using the Mann-Whitney
      U test, we identified significant gender differences in the parameters of
      immunoglobulins (Ig) M (IgM), IgA, and IgE. Forty-seven percent of the patients
      had increased ASLO levels, and 37% had increased IgE levels. CONCLUSION:  An
      evaluation of a patient's serologic parameters and laboratory results may be
      relevant to the etiology and prevention of HBI. Based on the results obtained
      from the study sample, the identification of etiologic agents and causative
      factors remain a public health challenge that affects the quality of life of
      children.

PMID- 25992112
TI  - Gout of the temporomandibular joint: report of a case.
AB  - Introduction Gout is an illness characterized by the deposition of monosodium
      urate crystals in the joints or in soft tissues. The clinical manifestation
      results from inflammation of limb joints and pain with a rare presentation in the
      temporomandibular joint (TMJ). Case Report This study describes a 66-year-old
      white man with a chief complaint of "occasional pain in the left temporal muscle
      region." The case disclosed a gout manifestation in the TMJ after physical,
      radiographic, and ultrasonographic exams, and the patient was referred to proper
      treatment. Conclusion Gout manifestation in the TMJ is an unusual presentation,
      and few reports in the English literature address to the subject. Gout in the TMJ
      should be included as a differential diagnosis for joint disorders. 

PMID- 25992113
TI  - Sudden hemianopsia secondary to ethmoid sinus mucocele.
AB  - Paranasal sinus mucoceles are benign cystic lesions, filled with mucus, occurring
      due to an obstruction of involved sinus ostium. They are indolent, locally
      expansive, and destructive. Surgical treatment must be performed and, when done
      at the correct time, may prevent sequelae. We present a case of ethmoid sinus
      mucocele with orbit involvement and permanent optical nerve injury. 

PMID- 25992114
TI  - Intracochlear schwannoma: diagnosis and management.
AB  - Introduction Schwannomas of the eighth cranial nerve are benign tumors that
      usually occur in the internal auditory canal or the cerebellopontine angle
      cistern. Rarely, these tumors may originate from the neural elements within the
      vestibule, cochlea, or semicircular canals and are called intralabyrinthine
      schwannomas. Intracochlear schwannomas (ICSs) represent a small percentage of
      these tumors, and their diagnosis is based on high-resolution magnetic resonance
      imaging (MRI). Objectives To report the clinical and radiologic features and
      audiometric testing results of an ICS in a 48-year-old man after a 22-month
      follow-up period. Resumed Report A patient with an 8-year history of persistent
      tinnitus in his right ear, combined with ipsilateral progressive hearing loss and
      aural fullness. Audiometry revealed normal hearing in the left ear and a moderate
      to severe sensorineural hearing loss in the right ear, with decreased speech
      reception threshold and word recognition score, compared with the exam performed
      5 years previously. MRI showed a small intracochlear nodular lesion in the
      modiolus, isointense on T1 with a high contrast enhancement on T1 postgadolinium
      images. During the follow-up period, there were no radiologic changes on imaging
      studies. Thus, a wait-and-scan policy was chosen as the lesion remained stable
      with no considerable growth and the patient still presents with residual hearing.
      Conclusions Once diagnosed, not all ICS patients require surgery. Treatment
      options for ICS include stereotactic radiotherapy and rescanning policy,
      depending on the tumor's size, evidence of the tumor's growth, degree of hearing
      loss, intractable vestibular symptoms, concern about the pathologic diagnosis,
      and the patient's other medical conditions. 

PMID- 25992115
TI  - Giant fibrovascular polyp of the larynx.
AB  - Introduction Fibrovascular polyps (FVPs) are rare benign tumors originating in
      the cervical esophagus, and, rarely, in the hypopharynx. A case of FVP from the
      larynx has not yet been described in the literature. Objectives To discuss a
      unique case of FVP originating in the larynx. Resumed Report A 58-year-old woman
      presented with a 6-month history of progressive dysphagia. Endoscopic exams
      identified an elongated polypoid lesion originating from the mucosa of the
      epiglottis and the right pharyngoepiglottic fold. Excision of this mass under
      direct laryngoscopy revealed an 11.5 * 0.8-cm polypoid lesion, histologically
      diagnosed as an FVP. Conclusion The location of this FVP is important because,
      despite being a benign tumor, it carries a potentially lethal risk of upper
      airway obstruction. 

PMID- 25992116
TI  - Pleomorphic adenoma of the tongue base: case report and review.
AB  - Introduction Pleomorphic adenoma, also known as mixed tumor, is the most common
      benign tumor of the major and minor salivary glands. The occurrence of
      pleomorphic adenoma of the tongue base is very rare, and very few cases have been
      reported in the literature. Objective The authors present a rare case of
      pleomorphic adenoma of the tongue base and a review of the literature. Case
      Report A 55-year-old woman had an extensive cervical mass, with little pain, from
      the submental level to the level below the hyoid bone. Fiberoptic endoscopic
      examination showed an extensive mass at the base of the tongue with considerable
      reduction in the airway. Magnetic resonance image scan revealed a contrast
      enhancing mass of heterogeneous density over the base of the tongue of 8 * 8 * 7
      cm and a reduction of the hypopharyngeal airway. Biopsy of the lesion was
      performed along with a tracheostomy due to the bulging tongue base and acute
      respiratory failure. Histologic examination with an immunohistochemistry study
      revealed a diagnosis of pleomorphic adenoma. The excision of the tumor was
      performed by a lateral pharyngotomy approach and the total mass was excised.
      Conclusion The authors consider the rarity of this case and show that this is the
      11th and the largest pleomorphic adenoma reported in the English-language medical
      literature. 

PMID- 25992118
TI  - International archives of otorhinolaryngology-new developments!

PMID- 25992117
TI  - Sphenoid sinus inverted papilloma: a case report and literature review.
AB  - Introduction Inverted papilloma is a rare benign tumor of the nasal fossa, which
      usually originates from its lateral wall. Only 5% of cases demonstrate exclusive
      sinus involvement. Primary sphenoid sinus involvement is even rarer. Although
      considered a benign lesion, the tumor has a potentially invasive nature and has
      also been found to have an associated malignancy rate of 7 to 15%. Objectives To
      report a case of inverted nasal papilloma originating in a rare location: the
      sphenoid sinus. Resumed Report a 56-year-old woman, presented to our outpatient
      clinic complaining of frontal headache, occasional otalgia and recent
      forgetfulness. She was initially evaluated by a neurologist and then submitted to
      a head magnetic resonance imaging. A lesion was found to be filling both sphenoid
      sinuses. Sinus computed tomography showed an opacified sphenoid sinus with
      apparent bony integrity. The patient underwent sphenoidotomy through a transnasal
      endoscopic approach. A bleeding papillomatous lesion was identified. A biopsy was
      performed and histopathologic study suggested inverted papilloma. The lesion was
      then completely resected. The patient has been followed for 60 days after
      surgery; no signs of recurrence were found upon flexible nasofibroscope
      examination. Conclusion Inverted Papilloma exclusively involving the sphenoid
      sinus is a rare entity. Non specific symptomatology and Clinical presentation
      make this kind of tumor a diagnostic and therapeutic challenge. The Endoscopic
      Sphenoidotomy has been the treatment of choice. Close follow-up is required in
      order to detect possible recurrences and malignant transformation. 

PMID- 25992119
TI  - Babies' portal website hearing aid section: assessment by audiologists.
AB  - Introduction The family has ultimate responsibility for decisions about the use
      and care during the daily routine and problem solving in the manipulation of
      hearing aids (HA) in infants and children. Objective The purpose of the study was
      to assess technical and content quality of Babies' Portal website Hearing Aid
      section by audiologists. Methods Letters and e-mails were sent inviting
      professionals to surf the website and anonymously fill out an online form with 58
      questions covering demographic data as well as the website's technical (Emory
      questionnaire with the subscales of accuracy, authorship, updates, public,
      navigation, links, and structure) and content quality. Results A total of 109
      professionals (tree men and 106 women) with mean age of 31.6 years participated
      in the study. Emory percentage scores ranged from 90.1 to 96.7%. The Hearing Aid
      section contents were considered good or very good. Conclusion The website was
      deemed to have good technical and content quality, being suitable to supplement
      informational counseling to parents of hearing-impaired children fitted with
      hearing aids. 

PMID- 25992120
TI  - Dichotic hearing in elderly hearing aid users who choose to use a single-ear
      device.
AB  - Introduction Elderly individuals with bilateral hearing loss often do not use
      hearing aids in both ears. Because of this, dichotic tests to assess hearing in
      this group may help identify peculiar degenerative processes of aging and hearing
      aid selection. Objective To evaluate dichotic hearing for a group of elderly
      hearing aid users who did not adapt to using binaural devices and to verify the
      correlation between ear dominance and the side chosen to use the device. Methods
      A cross-sectional descriptive study involving 30 subjects from 60 to 81 years
      old, of both genders, with an indication for bilateral hearing aids for over 6
      months, but using only a single device. Medical history, pure tone audiometry,
      and dichotic listening tests were all completed. Results All subjects (100%) of
      the sample failed the dichotic digit test; 94% of the sample preferred to use the
      device in one ear because bilateral use bothered them and affected speech
      understanding. In 6%, the concern was aesthetics. In the dichotic digit test,
      there was significant predominance of the right ear over the left, and there was
      a significant correlation between the dominant side with the ear chosen by the
      participant for use of the hearing aid. Conclusion In elderly subjects with
      bilateral hearing loss who have chosen to use only one hearing aid, there is
      dominance of the right ear over the left in dichotic listening tasks. There is a
      correlation between the dominant ear and the ear chosen for hearing aid fitting. 

PMID- 25992121
TI  - Premalignant laryngeal lesions: twenty-year experience in specialized service.
AB  - Introduction Premalignant lesions are considered both a hyperplastic and
      dysplastic stage of epithelial lesions in the glottic larynx that may or may not
      progress into an invasive carcinoma. The evolution of laryngoscopic procedures in
      outpatients has provided better access to important information for safe and easy
      diagnosis of laryngeal pathologies. Objective The goal of this study was to
      determine the accuracy of the preoperative exam for diagnosis of premalignant
      laryngeal lesions and their connection with benign diseases of the vocal folds,
      as well as to assess their epidemiologic characteristics. Methods This is a
      retrospective and longitudinal cohort study performed through the review of
      surgical records of patients who underwent laryngeal microsurgery performed by a
      single surgeon from 1990 to 2009. Results Preoperative assessment of outpatients
      was 64.4% accurate. Vocal fold cysts were the most frequently associated benign
      lesions. The patients who apparently had premalignant lesions represented 10.57%
      of those who underwent laryngeal microsurgery. Premalignant lesions prevailed in
      men (69.49%) age from 41 to 50 years (32.20%). Conclusion Although the evolution
      of laryngoscopic procedures in outpatients has provided better access to
      important information for safe and easy diagnosis of laryngeal pathologies, about
      one-third of premalignant lesions are diagnosed just during the laryngeal
      microsurgery. Cysts were the most prevalent concomitant benign lesion of the
      vocal folds. Males were more prevalent than females and the predominant age
      bracket was between 41 and 50 years. 

PMID- 25992122
TI  - Important factors in the cognitive development of children with hearing
      impairment: case studies of candidates for cochlear implants.
AB  - Introduction The factors that affect the development of children with and without
      hearing disabilities are similar, provided their innate communication abilities
      are taken into account. Parents need to mourn the loss of the expected normally
      hearing child, and it is important that parents create bonds of affection with
      their child. Objective To conduct a postevaluation of the development and
      cognition of 20 candidates for cochlear implants between 1 and 13 years of age
      and to observe important factors in their development. Methods The following
      instruments were used in accordance with their individual merits: interviews with
      parents; the Vineland Social Maturity Scale; the Columbia Maturity Scale; free
      drawings; Bender and Pre-Bender testing; and pedagogical tests. Results The
      results are described. Conclusion Parental acceptance of a child's deafness
      proved to be the starting point for the child's verbal or gestural communication
      development, as well as for cognitive, motor, and emotional development. If the
      association between deafness and fine motor skills (with or without multiple
      disabilities) undermines the development of a child's speech, it does not greatly
      affect communication when the child interacts with his or her peers and receives
      maternal stimulation. Overprotection and poor sociability make children less
      independent, impairs their development, and causes low self-esteem. Further
      observational studies are warranted to determine how cochlear implants contribute
      to patient recovery. 

PMID- 25992123
TI  - Longitudinal Analysis of the Absence of Intraoperative Neural Response Telemetry
      in Children using Cochlear Implants.
AB  - Introduction Currently the cochlear implant allows access to sounds in
      individuals with profound hearing loss. The objective methods used to verify the
      integrity of the cochlear device and the electrophysiologic response of users
      have noted these improvements. Objective To establish whether the evoked compound
      action potential of the auditory nerve can appear after electrical stimulation
      when it is absent intraoperatively. Methods The clinical records of children
      implanted with the Nucleus Freedom (Cochlear Ltd., Australia) (CI24RE) cochlear
      implant between January 2009 and January 2010 with at least 6 months of use were
      evaluated. The neural response telemetry (NRT) thresholds of electrodes 1, 6, 11,
      16, and 22 during surgery and after at least 3 months of implant use were
      analyzed and correlated with etiology, length of auditory deprivation, and
      chronological age. These data were compared between a group of children
      exhibiting responses in all of the tested electrodes and a group of children who
      had at least one absent response. Results The sample was composed of clinical
      records of 51 children. From these, 21% (11) showed no NRT in at least one of the
      tested electrodes. After an average of 4.9 months of stimulation, the number of
      individuals exhibiting absent responses decreased from 21 to 11% (n = 6).
      Conclusion It is feasible that absent responses present after a period of
      electrical stimulation. In our sample, 45% (n = 5) of the patients with
      intraoperative absence exhibited a positive response after an average of 4.9
      months of continued electrical stimulation. 

PMID- 25992124
TI  - Masticatory changes as a result of oral disorders in smokers.
AB  - Introduction For chewing to occur properly, it is necessary that all oral
      structures are present and of normal standard. Objectives The aim of this study
      is to verify the presence of oral changes in smokers and the impact of the
      changes on masticatory function compared with individuals who never smoked.
      Methods Forty-eight subjects were evaluated, split into two study groups (24
      subjects each) of current tobacco users and individuals who have never smoked.
      The variables halitosis, presence of lesions suggestive of caries and periodontal
      problems, number of teeth, classification of malocclusions according to angle,
      standard grinding food, chewing pattern, and speed of chewing were evaluated.
      Results There was no statistically significant difference in tooth loss between
      the groups, but the smokers had more losses manifesting malocclusion. Most
      smokers had halitosis and lesions suggestive of caries and periodontal problems;
      the halitosis was associated with the latter variable. Masticatory speed was also
      reduced significantly in these individuals compared with the control group when
      associated with occlusal alterations, in addition to grinding food with the
      tongue. No difference was observed regarding the chewing pattern. The presence of
      halitosis and periodontal problems were more common in those who smoke more than
      20 years. Conclusion There is an association between smoking and dental changes,
      which cause increased masticatory changes. 

PMID- 25992125
TI  - The impact of acute loss of weight on eustachian tube function.
AB  - Introduction The eustachian tube is one of the key structures responsible for the
      functional balance of the middle ear. Some clinical conditions associated with
      tubal malfunction can cause extremely unpleasant symptoms. These symptoms could
      be triggered by acute loss of weight, for example, after bariatric surgery.
      Objective To evaluate the frequency and intensity of auditory tube dysfunction
      symptoms in obese patients after bariatric surgery. Methods Nineteen patients
      with accepted formal indications for bariatric surgery underwent a hearing
      evaluation (otoscopy, tonal and vocal audiometry, and impedanceometry) and a
      hearing questionnaire before, at the time of, 3 months after surgery (first
      postoperative evaluation), and 6 months (second postoperative evaluation) after
      surgery. Patients with a history of ear disease or ear surgery were excluded.
      Results None of the patients reported tubal dysfunction symptoms before surgery.
      Postsurgical results showed that 5 (26.3%) patients presented symptoms related to
      dysfunction of the eustachian tube at the first postoperative evaluation. After
      the 6-month follow-up, 9 (47.3%) patients reported symptoms of tubal dysfunction.
      Conclusion This study suggests that bariatric surgery can cause symptoms of
      eustachian tube dysfunction, probably due to rapid weight loss and the consequent
      loss of peritubal fat. 

PMID- 25992126
TI  - Epidemiologic profile of an otolaryngologic emergency service.
AB  - Introduction According to current research, the number of patients seen in the
      emergency room is progressively increasing. There are few studies on the
      characteristics of ear, nose, and throat diseases treated in the emergency room.
      Objectives (1) To establish the epidemiologic profile of patients with these
      complaints treated at a referral emergency hospital in locoregional city
      Curitiba, and (2) to evaluate the calls that truly required emergency care.
      Methods This is a contemporary cross-study of urgent and emergency referrals to a
      hospital with otolaryngologic services during the year 2012. Data were collected
      and epidemiologic characteristics analyzed. Results We analyzed 1,067 patients:
      312 presented in spring, 255 in summer, 253 in autumn, and 247 in winter. We
      found 17 diseases that were common during the year, with 244 (23.99%) upper
      respiratory tract infections being the most frequent disease. There was no
      statistically significant difference in the incidence of diseases, except that
      acute otitis media was most common during the summer (p = 0.02); distribution
      between the sexes was balanced. The predominant age group was adults. We found
      9.27% cases were true emergencies. Conclusion Patients were 20 to 40 years, with
      upper respiratory tract infection the most incident disease; 9.27% of cases were
      emergencies. 

PMID- 25992127
TI  - Association between Ear Fullness, Earache, and Temporomandibular Joint Disorders
      in the Elderly.
AB  - Introduction An earache (otalgia or ear pain) is pain in one or both ears that
      may last a short or long time. Earache is prevalent in the population with
      temporomandibular joint disorders (TMJDs), but there is a dearth of epidemiologic
      studies regarding the association between TMJD and ear pain and ear fullness in
      older people. Objective To assess the presence of earache and ear fullness in
      elderly patients with TMJD. Methods A cross-sectional study was conducted in
      independently living, elderly individuals. TMJD was assessed by dental evaluation
      and earache was verified by medical history. Statistical analysis was performed
      using the chi-square test and relative risk. Results Of the 197 subjects
      evaluated in this part of the study, 22 had earache, and 35 was verified by ear
      fullness. Of the 22 subjects with earache, none had conductive or mixed hearing
      loss in the ears tested. There was a significant association (p = 0.036) between
      the TMJD and earache (odds ratio = 2.3), but there was no significant association
      between the TMJD and ear fullness. Conclusion These results highlight the
      importance of identifying risk factors for earache that can be modified through
      specific interventions, which is essential in the prevention of future episodes,
      as well as managing the process of treatment of elderly patients in general. 

PMID- 25992128
TI  - Physical activity in the prevention of benign paroxysmal positional vertigo:
      probable association.
AB  - Introduction Physical inactivity is an important risk factor for many age-related
      diseases and symptoms such as dizziness and vertigo. Objective The aim of the
      study was to investigate the possible association between benign paroxysmal
      positional vertigo (BPPV) and regular physical activity in elderly subjects.
      Methods This cross-sectional study included 491 elderly individuals who lived
      independently. Physical exercise was assessed through a questionnaire and BPPV by
      history and the Dix-Hallpike maneuver. Results The present study indicates no
      significant association between BPPV with lack of physical activity in men and in
      the total population. We have confirmed associations between BPPV with lack of
      physical activity in women (p = 0.01). Women with a sedentary lifestyle who do
      not practice physical activity are 2.62 more likely to have BPPV than those with
      regular physical activity. Conclusion These results highlight the importance of
      identifying risk factors for BPPV that can be modified through specific
      interventions. Regular physical activity is a lifestyle with potential to
      decrease the risk of vertigo in women. 

PMID- 25992130
TI  - Membrane stress proclivities in the Mammalian labyrinth.
AB  - Introduction The membranes of the inferior division of the labyrinth in some
      mammals appear more vulnerable to hydropic distention than those of the superior
      division. This finding in guinea pigs, cats, and humans has been attributed to
      the evidently thinner membranes with implied higher stress levels. Objective The
      objective of this study is to identify other configurational features, if any,
      that may contribute to membrane stress proclivity and therefore might act to
      augment or ameliorate stress in the several chambers of the membranous labyrinth.
      Methods Stress proclivity can be investigated using shell theory to analyze a
      geometric model of the labyrinthine membranes in mammals. Such an approach can
      provide the necessary mathematical descriptions of stress in each chamber of the
      labyrinth. Results Stress proclivity depends on three physical features: membrane
      thickness, radial size, and chamber shape. Lower stress proclivities are
      projected for smaller chambers with thick, highly synclastic membranes. Higher
      stress levels are projected for larger chambers with thin, flat, or anticlastic
      membranes. Conclusions In the mammalian labyrinth, pars superior chambers exhibit
      permutations of membrane thickness, size, and favorable shapes that reduce stress
      proclivity. In contrast, the pars inferior chambers are characterized by thin
      membranes with flat contours and adverse shapes that make them especially
      vulnerable to hydropic distention. 

PMID- 25992129
TI  - Sensitization Profile to Allergens in Patients Using Multi-Test II.
AB  - Introduction Medical intervention in allergies has broadened its perspective,
      also focusing in the quality of life of patients. Patients are instructed, before
      using pharmacotherapy agents, to avoid the causal agent. Objective This study
      aims to analyze the sensitization profile of patients with allergic complaints
      and identify possible characteristics specific to each age group and gender.
      Methods A descriptive cross-sectional study included data collected from medical
      records (from Multi-Test II database, Lincoln Diagnostics Inc. Decatur, Illinois)
      of 1,912 patients who underwent skin prick test from March to October 2013.
      Patients were organized and analyzed according to gender, age, and results of the
      allergens subtypes tested. Results The study was composed of 1,912 patients (60%
      male and 40% female) of ages between 3 and 87 years. Positive tests were more
      prevalent in quantity and intensity with the mites Dermatophagoides pteronyssinus
      and Dermatophagoides farinae, each with 60% of the total analyzed. In second
      place were pollens, especially Dactylis glomerata and Festuca pratensis.
      Conclusion The female and male sexes were equally atopic. Fungi and epithelia of
      dog and cat were not considered potential aeroallergens that could cause
      symptoms. However, mites are common in Parana, Brazil. Further studies regarding
      the pollens are needed, as this study result diverged from the literature. 

PMID- 25992131
TI  - Extranasopharyngeal angiofibroma originating in the inferior turbinate: a
      distinct clinical entity at an unusual site.
AB  - Introduction The extranasopharyngeal angiofibroma is histologically similar to
      juvenile nasopharyngeal angiofibroma, differing from the latter in clinical and
      epidemiologic characteristics. Objectives We present a case of
      extranasopharyngeal angiofibroma originating in the inferior turbinate. Resumed
      Report The patient was a girl, 8 years and 6 months of age, who had constant
      bilateral nasal obstruction and recurrent epistaxis for 6 months, worse on the
      right side, with hyposmia and snoring. Nasal endoscopy showed a reddish lesion,
      smooth, friable, and nonulcerated. Computed tomography showed a lesion with soft
      tissue density in the right nasal cavity. We used an endoscopic approach and
      found the lesion inserted in the right inferior turbinate. We did a subperiosteal
      dissection and excision with a partial turbinectomy with a resection margin of
      0.5 cm. Histopathology reported it to be an extranasopharyngeal angiofibroma.
      Conclusion Although rare, extranasopharyngeal angiofibroma should be considered
      in the diagnosis of vascular tumors of the head and neck. 

PMID- 25992132
TI  - Sinus histiocytosis with massive lymphadenopathy (rosai-dorfman disease): a case
      report and literature review.
AB  - Introduction Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative
      disorder of unknown etiology. Usually it presents with massive painless cervical
      lymph node enlargement. Histologically, it shows proliferation of distinctive
      histiocytic cells that demonstrate emperipolesis in the background of a mixed
      inflammatory infiltrates. Immunohistochemically, the cells are positive for
      markers such as CD68 and S100. Objective To report a case of a 12-year-old
      patient with multiple sites of cervical lymphadenitis, which was diagnosed as RDD
      histopathologically as well as immunohistologically. Resumed Report A 12-year-old
      girl presented with multiple painless sites of cervical lymphadenitis without any
      systemic and other ear, nose, and throat manifestations. The biopsy report of the
      lymph node showed dilatation of the sinuses, filled with histiocytes having foamy
      cytoplasm. Many of the histiocytes were engulfing mature lymphocytes. The sinus
      histiocytes were strongly positive for S-100 protein. Conclusion RDD must be
      considered in the differential diagnosis of massive or multiple
      lymphadenopathies. 

PMID- 25992133
TI  - Angioleiomyoma of the nasal cavity.
AB  - Introduction Vascular leiomyoma of the nasal cavity is an extremely rare tumor
      that represents less than 1% of all vascular leiomyomas. It is more prevalent in
      women between the fourth and sixth decades, reaching primarily the inferior nasal
      turbinates. Objectives Reporting and assisting the systematization of more
      accurate diagnostic methods in clinical and complementary investigation of
      vascular leiomyoma in the nasal cavity. Resumed Report We present the case of a
      49-year-old woman diagnosed with vascular leiomyoma in the nasal cavity, which
      manifested mainly with nasal obstruction. During investigation, computer
      tomography was not diagnostic, the cytologic study was not conclusive, and
      according to the biopsy, it was a squamous papilloma. Conclusion We suggest that
      the technical difficulty in obtaining an adequate amount of material for
      preoperative biopsy, associated with the topography of the lesion in the
      vestibular nasal region, may have contributed to changing the postoperative
      diagnosis. Thus, pathologic study of the surgical fragment is the more accurate
      method for diagnosis. 

PMID- 25992134
TI  - An unusual complication of chronic suppurative otitis media: bezold abscess
      progressing to scapular abscess.
AB  - Introduction Suppurative otitis media is still the most common ear disease in
      developing countries. Otogenic complications of this disease have decreased
      considerably because of the advent of antibiotics, and few rare complications
      have been encountered. Objective To report a case of a patient with scapular
      abscess and lumber cellulitis that had progressed from Bezold abscess as a
      complication of squamous-type chronic suppurative otitis media. Resumed Report A
      14-year-old girl presented with foul-smelling, purulent, left ear discharge of 1
      year duration and decreased hearing on same ear of 6-month duration. She
      developed painful swelling in left side of neck with restricted neck movement and
      high-grade fever of 3-day duration and swelling over the left scapular area of 1
      day duration. The examination and investigation diagnosed squamous-type chronic
      suppurative otitis media with Bezold abscess progressing to scapular abscess and
      lumber cellulitis. Final Comment Chronic suppurative otitis media can lead to
      abscess in any part of body. 

PMID- 25992135
TI  - Skull base surgery in the 21st century: accelerated revolution.

PMID- 25992136
TI  - Advances in computed tomography evaluation of skull base diseases.
AB  - Introduction Computed tomography (CT) is a key component in the evaluation of
      skull base diseases. With its ability to clearly delineate the osseous anatomy,
      CT can provide not only important tips to diagnosis but also key information for
      surgical planning. Objectives The purpose of this article is to describe some of
      the main CT imaging features that contribute to the diagnosis of skull base
      tumors, review recent knowledge related to bony manifestations of these
      conditions, and summarize recent technological advances in CT that contribute to
      image quality and improved diagnosis. Data Synthesis Recent advances in CT
      technology allow fine-detailed evaluation of the bony anatomy using
      submillimetric sections. Dual-energy CT material decomposition capabilities allow
      clear separation between contrast material, bone, and soft tissues with many
      clinical applications in the skull base. Dual-energy technology has also the
      ability to decrease image degradation from metallic hardwares using some
      techniques that can result in similar or even decreased radiation to patients.
      Conclusions CT is very useful in the evaluation of skull base diseases, and
      recent technological advances can increase disease conspicuity resulting in
      improved diagnostic capabilities and enhanced surgical planning. 

PMID- 25992137
TI  - Advances in magnetic resonance imaging of the skull base.
AB  - Introduction Over the past 20 years, magnetic resonance imaging (MRI) has
      advanced due to new techniques involving increased magnetic field strength and
      developments in coils and pulse sequences. These advances allow increased
      opportunity to delineate the complex skull base anatomy and may guide the
      diagnosis and treatment of the myriad of pathologies that can affect the skull
      base. Objectives The objective of this article is to provide a brief background
      of the development of MRI and illustrate advances in skull base imaging,
      including techniques that allow improved conspicuity, characterization, and
      correlative physiologic assessment of skull base pathologies. Data Synthesis
      Specific radiographic illustrations of increased skull base conspicuity including
      the lower cranial nerves, vessels, foramina, cerebrospinal fluid (CSF) leaks, and
      effacement of endolymph are provided. In addition, MRIs demonstrating
      characterization of skull base lesions, such as recurrent cholesteatoma versus
      granulation tissue or abscess versus tumor, are also provided as well as
      correlative clinical findings in CSF flow studies in a patient pre- and post
      suboccipital decompression for a Chiari I malformation. Conclusions This article
      illustrates MRI radiographic advances over the past 20 years, which have improved
      clinicians' ability to diagnose, define, and hopefully improve the treatment and
      outcomes of patients with underlying skull base pathologies. 

PMID- 25992138
TI  - Evolution of minimally invasive approaches to the sella and parasellar region.
AB  - Introduction Given advancements in endoscopic image quality, instrumentation,
      surgical navigation, skull base closure techniques, and anatomical understanding,
      the endonasal endoscopic approach has rapidly evolved into a widely utilized
      technique for removal of sellar and parasellar tumors. Although pituitary
      adenomas and Rathke cleft cysts constitute the majority of lesions removed via
      this route, craniopharyngiomas, clival chordomas, parasellar meningiomas, and
      other lesions are increasingly removed using this approach. Paralleling the
      evolution of the endonasal route to the parasellar region, the supraorbital
      eyebrow craniotomy has also been increasingly used as an alternative minimally
      invasive approach to reach this skull base region. Similar to the endonasal
      route, the supraorbital route has been greatly facilitated by advances in
      endoscopy, along with development of more refined, low-profile instrumentation
      and surgical navigation technology. Objectives This review, encompassing both
      transcranial and transsphenoidal routes, will recount the high points and
      advances that have made minimally invasive approaches to the sellar region
      possible, the evolution of these approaches, and their relative indications and
      technical nuances. Data Synthesis The literature is reviewed regarding the
      evolution of surgical approaches to the sellar region beginning with the earliest
      attempts and emphasizing technological advances, which have allowed the evolution
      of the modern technique. The surgical techniques for both endoscopic
      transsphenoidal and supraorbital approaches are described in detail. The relative
      indications for each approach are highlighted using case illustrations.
      Conclusions Although tremendous advances have been made in transitioning toward
      minimally invasive transcranial and transsphenoidal approaches to the sella,
      further work remains to be done. Together, the endonasal endoscopic and the
      supraorbital endoscope-assisted approaches are complementary minimally invasive
      routes to the parasellar region. 

PMID- 25992139
TI  - Esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated
      carcinoma: differentiation in diagnosis and treatment.
AB  - Introduction Malignant sinonasal tumors comprise less than 1% of all neoplasms. A
      wide variety of tumors occurring primarily in this site can present with an
      undifferentiated or poorly differentiated morphology. Among them are
      esthesioneuroblastomas, sinonasal undifferentiated carcinomas, and neuroendocrine
      carcinomas. Objectives We will discuss diagnostic strategies, recent advances in
      immunohistochemistry and molecular diagnosis, and treatment strategies. Data
      Synthesis These lesions are diagnostically challenging, and up to 30% of
      sinonasal malignancies referred to the University of Texas MD Anderson Cancer
      Center are given a different diagnosis on review of pathology. Correct
      classification is vital, as these tumors are significantly different in
      biological behavior and response to treatment. The past decade has witnessed
      advances in diagnosis and therapeutic modalities leading to improvements in
      survival. However, the optimal treatment for esthesioneuroblastoma, sinonasal
      undifferentiated carcinoma, and neuroendocrine carcinoma remain debated. We
      discuss advances in immunohistochemistry and molecular diagnosis, diagnostic
      strategies, and treatment selection. Conclusions There are significant
      differences in prognosis and treatment for esthesioneuroblastoma, neuroendocrine
      carcinoma, and sinonasal undifferentiated carcinoma. Recent advances have the
      potential to improve oncologic outcomes but further investigation in needed. 

PMID- 25992140
TI  - Nuances in the treatment of malignant tumors of the clival and petroclival
      region.
AB  - Introduction Malignancies of the clivus and petroclival region are mainly
      chordomas and chondrosarcomas. Although a spectrum of malignancies may present in
      this area, a finite group of commonly encountered malignant pathologies will be
      the focus of this review, as they are recognized to be formidable pathologies due
      to adjacent critical neurovascular structures and challenging surgical
      approaches. Objectives The objective is to review the literature regarding
      medical and surgical management of malignant tumors of the clival and petroclival
      region with a focus on clinical presentation, diagnostic identification, and
      associated adjuvant therapies. We will also discuss our current treatment
      paradigm using endoscopic, open, and combined approaches to the skull base. Data
      Synthesis A literature review was conducted, searching for basic science and
      clinical evidence from PubMed, Medline, and the Cochrane Database. The selection
      criteria encompassed original articles including data from both basic science and
      clinical literature, case series, case reports, and review articles on the
      etiology, diagnosis, treatment, and management of skull base malignancies in the
      clival and petroclival region. Conclusions The management of petroclival
      malignancies requires a multidisciplinary team to deliver the most complete
      surgical resection, with minimal morbidity, followed by appropriate adjuvant
      therapy. We advocate the combination of endoscopic and open approaches
      (traditional or minimally invasive) as required by the particular tumor followed
      by radiation therapy to optimize oncologic outcomes. 

PMID- 25992141
TI  - Management of carotid artery injury in endonasal surgery.
AB  - Introduction Carotid artery injury (CAI) is the most feared and potentially
      catastrophic intraoperative complication an endoscopic skull base surgeon may
      face. With the advancement of transnasal endoscopic surgery and the willingness
      to tackle more diverse pathology, evidence-based management of this life
      threatening complication is paramount for patient safety and surgeon confidence.
      Objectives We review the current English literature surrounding the management of
      CAI during endoscopic transnasal surgery. Data Synthesis The searched databases
      included PubMed, MEDLINE, Cochrane database, LILACS, and BIREME. Keywords
      included "sinus surgery," "carotid injury," "endoscopic skull base surgery,"
      "hemostasis," "transsphenoidal" and "pseudoaneurysm." Conclusions Review of the
      literature found the incidence of CAI in endonasal skull base surgery to be as
      high as 9% in some surgeries. Furthermore, current treatment recommendations can
      result in damage to critical neurovascular structures. Management decisions must
      be made in the preoperative, operative, and postoperative setting to ensure
      adequate treatment of CAI and the prevention of its complications such as
      pseudoaneurysm. Emphasis should be placed on surgical competency, teamwork, and
      technical expertise through education and training. 

PMID- 25992143
TI  - Anatomopathology of the superstructure of the stapes in patients with
      otosclerosis.
AB  - Introduction Otosclerosis is a disease that causes bone resorption and deposition
      in the auditory structures, leading to deafness. Many studies have evaluated the
      histopathology of the stapes footplate in this disease (osteoblasts, osteoclasts,
      vascular proliferation, fibroblasts, and histiocytes), but we found no studies in
      the literature involving the histology of the superstructure of the stapes.
      Objectives To perform an analysis under optical microscopy of histopathologic
      findings of the superstructure of the stapes from patients with otosclerosis.
      Methods A contemporary cross-sectional cohort study of pathology analysis of
      superstructures of the stapes of patients with otosclerosis. Results Fifteen
      superstructures of stapes in patients with otosclerosis operated in our service
      and four stapes of cadavers used for dissection (controls) were evaluated. No
      areas of bone resorption or deposition or presence of osteoclasts and osteoblasts
      in the superstructure of the stapes were found. However, we found in the more
      distal portions of the crura areas with prominent cementitious lines and woven
      bone, which was different than the mature trabecular bone found in the head of
      the stapes or in the controls. Conclusion There were histologic changes in the
      superstructure of the stapes in patients with otosclerosis operated in our
      service. 

PMID- 25992142
TI  - Panorama of reconstruction of skull base defects: from traditional open to
      endonasal endoscopic approaches, from free grafts to microvascular flaps.
AB  - Introduction A substantial body of literature has been devoted to the distinct
      characteristics and surgical options to repair the skull base. However, the skull
      base is an anatomically challenging location that requires a three-dimensional
      reconstruction approach. Furthermore, advances in endoscopic skull base surgery
      encompass a wide range of surgical pathology, from benign tumors to sinonasal
      cancer. This has resulted in the creation of wide defects that yield a new
      challenge in skull base reconstruction. Progress in technology and imaging has
      made this approach an internationally accepted method to repair these defects.
      Objectives Discuss historical developments and flaps available for skull base
      reconstruction. Data Synthesis Free grafts in skull base reconstruction are a
      viable option in small defects and low-flow leaks. Vascularized flaps pose a
      distinct advantage in large defects and high-flow leaks. When open techniques are
      used, free flap reconstruction techniques are often necessary to repair large
      entry wound defects. Conclusions Reconstruction of skull base defects requires a
      thorough knowledge of surgical anatomy, disease, and patient risk factors
      associated with high-flow cerebrospinal fluid leaks. Various reconstruction
      techniques are available, from free tissue grafting to vascularized flaps.
      Possible complications that can befall after these procedures need to be
      considered. Although endonasal techniques are being used with increasing
      frequency, open techniques are still necessary in selected cases. 

PMID- 25992144
TI  - Audiological findings in patients with oculo-auriculo-vertebral spectrum.
AB  - Introduction Oculo-auriculo-vertebral spectrum, also referred to as Goldenhar
      syndrome, is a condition characterized by alterations involving the development
      of the structures of the first and second branchial arches. The abnormalities
      primarily affect the face, the eyes, the spine, and the ears, and the auricular
      abnormalities are associated with possible hearing loss. Objective To analyze the
      audiological findings of patients with oculo-auriculo-vertebral spectrum through
      liminal pure-tone audiometry and speech audiometry test. Methods Cross-sectional
      study conducted on 10 patients with oculo-auriculo-vertebral spectrum and
      clinical findings on at least two of the following areas: orocraniofacial,
      ocular, auricular, and vertebral. All patients underwent tonal and vocal hearing
      evaluations. Results Seven patients were male and three were female; all had ear
      abnormalities, and the right side was the most often affected. Conductive hearing
      loss was the most common (found in 10 ears), followed by sensorineural hearing
      loss (in five ears), with mixed hearing loss in only one ear. The impairment of
      the hearing loss ranged from mild to moderate, with one case of profound loss.
      Conclusions The results show a higher frequency of conductive hearing loss among
      individuals with the oculo-auriculo-vertebral spectrum phenotype, especially
      moderate loss affecting the right side. Furthermore, research in auditory
      thresholds in the oculo-auriculo-vertebral spectrum is important in speech
      therapy findings about the disease to facilitate early intervention for possible
      alterations. 

PMID- 25992145
TI  - Intraoperative Neural Response Telemetry and Neural Recovery Function: a
      Comparative Study between Adults and Children.
AB  - Introduction Neural response telemetry (NRT) is a method of capturing the action
      potential of the distal portion of the auditory nerve in cochlear implant (CI)
      users, using the CI itself to elicit and record the answers. In addition, it can
      also measure the recovery function of the auditory nerve (REC), that is, the
      refractory properties of the nerve. It is not clear in the literature whether the
      responses from adults are the same as those from children. Objective To compare
      the results of NRT and REC between adults and children undergoing CI surgery.
      Methods Cross-sectional, descriptive, and retrospective study of the results of
      NRT and REC for patients undergoing IC at our service. The NRT is assessed by the
      level of amplitude (microvolts) and REC as a function of three parameters: A
      (saturation level, in microvolts), t0 (absolute refractory period, in seconds),
      and tau (curve of the model function), measured in three electrodes (apical,
      medial, and basal). Results Fifty-two patients were evaluated with intraoperative
      NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No
      statistically significant difference was found between intraoperative responses
      of adults and children for NRT or for REC's three parameters, except for
      parameter A of the basal electrode. Conclusion The results of intraoperative NRT
      and REC were not different between adults and children, except for parameter A of
      the basal electrode. 

PMID- 25992146
TI  - Childhood hearing health: educating for prevention of hearing loss.
AB  - Introduction The presence of noise in our society has attracted the attention of
      health professionals, including speech-language pathologists, who have been
      charged along with educators with developing hearing conservation programs in
      schools. Objective To describe the results of three strategies for awareness and
      hearing preservation in first to fourth grades in public elementary schools.
      Methods The level of environmental noise in classrooms was assessed, and 638
      elementary school students from first to fourth grades, 5 to 10 years of age,
      were audiologically evaluated. After the evaluations, educational activities were
      presented to children and educators. Results The noise level in the classroom
      ranged from 71.8 to 94.8 A-weighted decibels. The environment of the classroom
      was found to promote sound reverberation, which hinders communication. Thirty-two
      students (5.1%) presented hearing alterations. Conclusion The application of
      strategies for a hearing conservation program at the school showed that noise is
      present in the room, and hearing loss, sometimes silent, affects schoolchildren.
      Students and teachers were aware that hearing problems can be prevented. Avoiding
      exposure to noise and improving the acoustics in classrooms are essential. 

PMID- 25992147
TI  - Hearing profile of brazilian forestry workers' noise exposure.
AB  - Introduction Researchers studying the hearing health of forestry workers have
      revealed the presence of a noise-induced hearing loss (NIHL) in this population
      and have concluded that the vibration of the equipment, the carbon monoxide
      released by motors, and pesticides might also contribute to NIHL. Objective To
      analyze the noise exposure in the Brazilian forestry industry workers and the
      effects on hearing. Methods The study sample comprised 109 employees of a company
      that specialized in reforestation. Their participants' mean age was 35.5 years
      (21 to 54 years), mean tenure at the company was 3.9 years (1 to 13 years), and
      mean total duration of noise exposure was 12.3 years (1 to 30 years). The
      existing documentation reporting on the jobs risk analysis was examined, noise
      level was measured, and pure tone audiometry was performed in all participants.
      Participants were divided into three groups according to their noise exposure
      levels in their current job. Results Of the participants who were exposed to
      noise levels less than 85 dBA (decibels with A-weighting filter), 23.8% had
      hearing loss, and 5.5% of the participants who were exposed to noise ranging from
      85 to 89.9 dBA and 11% of the participants who were exposed to noise greater than
      90 dBA had audiogram results suggestive of NIHL. Conclusion The implementation of
      a hearing loss prevention program tailored to forestry workers is needed. 

PMID- 25992148
TI  - Screening of connexin 26 in nonsyndromic hearing loss.
AB  - Introduction The first locus for nonsyndromic autosomal recessive hearing loss is
      on chromosome 13q11-22. The 35delG mutation is present in 80% of cases in which
      GJB2 is involved, which makes the study of this mutation very important. The
      viability and benefits of screening for mutations in the connexin 26 gene are now
      beginning to change the diagnostic evaluation and identification of the etiology
      of hearing loss. Objective To investigate the occurrence of the 35delG mutation
      in patients with nonsyndromic sensorineural hearing loss and their first degree
      relatives. Methods This transversal study included 72 patients from the local
      hospital. The patients were divided into three groups: group A, sensorineural
      hearing loss (n = 58); group B, first-degree relatives of group A with
      sensorineural hearing loss (n = 09); and group C, first-degree relatives of
      patients from group A without hearing loss (n = 05). All patients had
      audiological evaluation and genetic testing of the 35delG mutation. Results The
      35delG mutation was found in four heterozygous mutations (three of them found in
      the same family). The other heterozygous mutation was found in a female patient
      with bilateral, moderate, prelingual, sensorineural hearing loss. A single
      homozygous mutation was found in a male patient, with severe sensorineural
      hearing loss in his right ear and profound hearing loss in the left ear.
      Conclusions The 35delG mutation was found in 7% of the cases. The test is easy to
      perform and inexpensive, but it is necessary to investigate other genes related
      to hearing loss. 

PMID- 25992149
TI  - Prospective study of the surgical techniques used in primary rhinoplasty on the
      caucasian nose and comparison of the preoperative and postoperative
      anthropometric nose measurements.
AB  - Introduction The knowledge and study of surgical techniques and anthropometric
      measurements of the nose make possible a qualitative and quantitative analysis of
      surgical results. Objective Study the main technique used in rhinoplasty on
      Caucasian noses and compare preoperative and postoperative anthropometric
      measurements of the nose. Methods A prospective study with 170 patients was
      performed at a private hospital. Data were collected using the Electronic System
      Integrated of Protocols software (Sistema Integrado de Protocolos Eletronicos,
      SINPE(c)). The surgical techniques used in the nasal dorsum and tip were
      evaluated. Preoperative and 12-month follow-up photos as well as the measurements
      compared with the ideal aesthetic standard of a Caucasian nose were analyzed
      objectively. Student t test and standard deviation test were applied. Results
      There was a predominance of endonasal access (94.4%). The most common dorsum
      technique was hump removal (33.33%), and the predominance of sutures (24.76%) was
      observed on the nasal tip, with the lateral intercrural the most frequent
      (32.39%). Comparison between preoperative and postoperative photos found
      statistically significant alterations on the anthropometric measurements of the
      noses. Conclusion The main surgical techniques on Caucasian noses were evaluated,
      and a great variety was found. The evaluation of anthropometric measurements of
      the nose proved the efficiency of the performed procedures. 

PMID- 25992150
TI  - Is primary hyperparathyroidism a risk factor for papillary thyroid cancer? An
      exemplar study and literature review.
AB  - Introduction Primary hyperparathyroidism (PHPT) is associated with several cancer
      types, including papillary thyroid carcinoma (PTC). Objective To explore further
      the relation between PHPT and PTC. Methods By considering patients with PHPT as
      extra-suspicious for PTC, we studied an exemplar group of patients with PHPT with
      a small (<=1 cm) thyroid nodule, which was negative in preoperative cytologic
      examination. During parathyroidectomy, a frozen section biopsy of the thyroid
      nodule confirmed PTC, as did the final surgical specimen, revealing that the
      preoperative cytology was false-negative. Additionally, relevant reports
      retrieved from the English literature addressing thyroid cancer and
      hyperparathyroidism were reviewed and processed. Results Four patients with PHPT
      were studied. Three had a multifocal thyroid disease, and three had neck lymph
      node metastasis. Processing previous report data supported an association between
      PHPT and PTC. Although thyroid nodularity among patients with PHPT was similar to
      the general population, PTC incidence was higher. This was true also for patients
      with secondary hyperparathyroidism. Conclusions This study emphasized that PHPT
      should be considered as a noteworthy risk factor for PTC. Fine needle aspiration
      of a thyroid nodule is the most valuable diagnostic procedure for thyroid cancer.
      Yet, false-negative results were reported in up to 10% of cases, especially in
      small, subcentimeter nodules. In line with our data and the literature, patients
      with PHPT should have both a detailed ultrasound addressing the thyroid and
      cytology of any thyroid nodule, including small subcentimeter lesions. Moreover,
      surgical flexibility, allowing intraoperative thyroid nodule sampling, should be
      considered even for "innocent" nodules. 

PMID- 25992151
TI  - Quality of life in swallowing disorders after nonsurgical treatment for head and
      neck cancer.
AB  - Introduction Radiotherapy or chemoradiotherapy can result in severe swallowing
      disorders with potential risk for aspiration and can negatively impact the
      patient's quality of life (QOL). Objective To assess swallowing-related QOL in
      patients who underwent radiotherapy/chemoradiotherapy for head and neck cancer.
      Methods We interviewed 110 patients (85 men and 25 women) who had undergone
      exclusive radiotherapy (25.5%) or concomitant chemoradiotherapy (74.5%) from 6 to
      12 months before the study. The Quality of Life in Swallowing Disorders (SWAL
      QOL) questionnaire was employed to evaluate dysphagia-related QOL. Results The
      QOL was reduced in all domains for all patients. The scores were worse among men.
      There was a relationship between oral cavity as the primary cancer site and the
      fatigue domain and also between advanced cancer stage and the impact of food
      selection, communication, and social function domains. Chemoradiotherapy
      association, the presence of nasogastric tube and tracheotomy, and the
      persistence of alcoholism and smoking had also a negative effect on the QOL.
      Conclusions According to the SWAL-QOL questionnaire, the dysphagia-related impact
      on QOL was observed 6 to 12 months after the treatment ended. 

PMID- 25992152
TI  - Evaluation of swallowing in infants with congenital heart defect.
AB  - Introduction Surgical repair of congenital heart disease in the first years of
      life compromises the coordination of the suction, breathing, and swallowing
      functions. Objective To describe the alterations in swallowing found in infants
      with congenital heart defect during their hospitalization. Methods Prospective,
      cross-sectional study in a reference hospital for heart disease. The sample
      consisted of 19 postsurgical patients who underwent an evaluation of swallowing.
      The infants included were younger than 7 months and had a diagnosis of congenital
      heart defect and suspected swallowing difficulties. Results Of the 19 infants
      with congenital heart defect, the median age was 3.2 months. A significant
      association was found between suction rhythm and dysphagia (p = 0.036) and
      between oral-motor oral feeding readiness and dysphagia (p = 0.014). Conclusions
      The data suggest that dysphagia often occurs after surgery in infants with
      congenital heart defect. Infants with congenital heart defect had very similar
      behavior to preterm infants in terms of oral feeding readiness. 

PMID- 25992153
TI  - Vocal Variability Post Swallowing in Individuals with and without Oropharyngeal
      Dysphagia.
AB  - Introduction Voice modification after swallowing may indicate changes in the
      transit of the bolus. Objective The aim of this study is to verify the use of
      perceptual voice analysis to detect oropharyngeal dysphagia. Study Design Case
      series. Methods Twenty-seven patients with dysphagia as diagnosed by
      videofluoroscopy and 25 without were evaluated. The sustained vowel /a/ was
      recorded before this exam and after swallowing different consistencies (pasty,
      liquid and solid). For the voice evaluation, the GRBAS scale (grade, roughness,
      breathiness, asthenia and strain) and the parameter "wet voice" were used. Three
      judges blinded to study group and time of emission performed voice analysis.
      Results Individuals with dysphagia showed significant decrease in grade of voice
      and asthenia and increase in strain after swallowing pasty substances, differing
      from individuals without dysphagia who showed no modification of the parameters
      after swallowing. The wet voice parameter showed no difference after swallowing
      in both study groups. Conclusion The decrease in grade and asthenia and increased
      strain are indicative of a swallowing disorder, indicating increased vocal strain
      to clean the vocal tract of food. The modification of vocal production after
      swallowing proved to be a trusted resource for detection of swallowing disorders.

PMID- 25992154
TI  - Sleep respiratory disorders and clinical profile in patients with type 2 diabetes
      mellitus.
AB  - Introduction Sleep respiratory disorders (SRDs) are often found in patients with
      type 2 diabetes mellitus (T2DM). Objective The aim was to establish the
      prevalence of risk to develop an SRD using the Clinical Berlin Questionnaire
      (CBQ) and Epworth Sleepiness Scale (ESS) in patients with T2DM and verifying the
      correlation of anthropometric measurements and life quality (LQ) with ESS.
      Methods A descriptive and analytical study of a case series evaluating 208
      patients with T2DM, submitted to clinical and biochemical evaluation and
      implementation of CBQ, ESS, and WHOQOL-bref to evaluate LQ. Results Mean age was
      60.8 +/- 8.8 years, and 65.4% were women. Most diabetics were overweight (36.1%),
      and 29.8% were class I obese. One-third had positive risk signals for a SRD, with
      87.0 and 34.1% having high risk in CBQ and sleep disorders in ESS, respectively.
      There was a significant difference in the general LQ between the low- and high
      risk groups in the CBQ. Conclusion In this scenario, it is noteworthy that the
      active search for sleep disorders must start from simple methods, such as
      application of protocols. 

PMID- 25992155
TI  - Relationship between Dysphagia and Exacerbations in Chronic Obstructive Pulmonary
      Disease: A Literature Review.
AB  - Introduction The literature presents studies correlating chronic obstructive
      pulmonary disease to dysphagia and suggesting that the aspiration laryngeal
      phenomenon related to changes in the pharyngeal phase contributes significantly
      to the exacerbation of symptoms of lung disease. Objectives This study aimed to
      conduct a literature review to identify the relation between dysphagia and
      exacerbations of chronic obstructive pulmonary disease. Data Synthesis We found
      21 studies and included 19 in this review. The few studies that related to the
      subject agreed that the presence of dysphagia, due to lack of coordination
      between swallowing and breathing, may be one of the triggering factors of chronic
      obstructive pulmonary disease exacerbation. Conclusions The review noted that
      there is a relationship between dysphagia and exacerbations of chronic
      obstructive pulmonary disease, identified by studies demonstrating that the
      difficulties associated with swallowing may lead to exacerbation of the disease.
      There was difficulty in comparing studies by their methodological differences.
      More research is needed to clarify the relationship between dysphagia and
      exacerbations of chronic obstructive pulmonary disease, making it possible to
      develop multiprofessional treatment strategies for these patients, catered to
      specific needs due to the systemic manifestations of the disease. 

PMID- 25992156
TI  - Predictors of success in the treatment of obstructive sleep apnea syndrome with
      mandibular repositioning appliance: a systematic review.
AB  - Introduction Obstructive sleep apnea syndrome affects up to 4% of middle-aged men
      and 2% of adult women. It is associated with obesity. Objective The objective of
      this article is to review the literature to determine which factors best
      correlate with treatment success in patients with obstructive sleep apnea
      syndrome treated with a mandibular repositioning appliance. Data Synthesis A
      search was performed of the PubMed, Cochrane, Lilacs, Scielo, and Web of Science
      databases of articles published from January 1988 to January 2012. Two review
      authors independently collected data and assessed trial quality. Sixty-nine
      articles were selected from PubMed and 1 from Cochrane library. Of these, 42 were
      excluded based on the title and abstract, and 27 were retrieved for complete
      reading. A total of 13 articles and 1 systematic review were considered eligible
      for further review and inclusion in this study: 6 studies evaluated
      anthropomorphic and physiologic factors, 3 articles addressed cephalometric and
      anatomic factors, and 4 studies evaluated variables related to mandibular
      repositioning appliance design and activation. All the studies evaluated had low
      to moderate methodologic quality and were not able to support evidence on
      prediction of treatment success. Conclusion Based on this systematic review on
      obstructive sleep apnea syndrome treatment, it remains unclear which predictive
      factors can be used with confidence to select patients suitable for treatment
      with a mandibular repositioning appliance. 

PMID- 25992157
TI  - Therapeutic options in idiopathic burning mouth syndrome: literature review.
AB  - Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation
      in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis
      and treatment for primary BMS are controversial. No specific laboratory tests or
      diagnostic criteria are well established, and the diagnosis is made by excluding
      all other possible disorders. Objective To review the literature on the main
      treatment options in idiopathic BMS and compare the best results of the main
      studies in 15 years. Data Synthesis We conducted a literature review on
      PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and
      only selected studies comparing different therapeutic options in idiopathic BMS,
      with preference for randomized and double-blind controlled studies. Final
      Comments Topical clonazepam showed good short-term results for the relief of
      pain, although this was not presented as a definitive cure. Similarly, alpha
      lipoic acid showed good results, but there are few randomized controlled studies
      that showed the long-term results and complete remission of symptoms. On the
      other hand, cognitive therapy is reported as a good and lasting therapeutic
      option with the advantage of not having side effects, and it can be combined with
      pharmacologic therapy. 

PMID- 25992158
TI  - Hairy polyp of the supratonsillar fossa causing intermittent airway obstruction.
AB  - Introduction Dermoids frequently called "hairy polyps" and their nature have not
      been completely clarified. Objectives To discuss the unusual presentation,
      symptoms, incidence, histology, and perioperative management of hairy polyps in
      the light of a case and current literature. Resumed Report A 3-year-old boy
      presented with intermittent respiratory distress since birth. Oropharyngeal
      examination revealed a nasopharyngeal mass originating from the supratonsillar
      fossa. The mass was so mobile that it moved between the oropharynx and the
      nasopharynx during swallowing. The radiologic and pathologic examinations
      confirmed the mass as a hairy polyp. Conclusion In a pediatric age group with
      airway obstruction, hairy polyps of the oropharyngeal region must also be
      included in the differential diagnosis. 

PMID- 25992159
TI  - Isolated schwannoma of the olfactory groove: a case report.
AB  - Introduction Schwannoma of the olfactory groove is an extremely rare tumor that
      can share a differential diagnosis with meningioma or neuroblastoma. Objectives
      The authors present a case of giant schwannoma involving the anterior cranial
      fossa and ethmoid sinuses. Case Report The patient presented with a 30-month
      history of left nasal obstruction, anosmia, and sporadic ipsilateral bleeding.
      Computed tomography of the paranasal sinuses revealed expansive lesion on the
      left nasal cavity extending to nasopharynx up to ethmoid and sphenoid sinuses
      bilaterally with intraorbital and parasellar extension to the skull base.
      Magnetic resonance imaging scan confirmed the expansive tumor without dural
      penetration. Biopsy revealed no evidence of malignancy and probable neural cell.
      Bifrontal craniotomy was performed combined with lateral rhinotomy (Weber
      Ferguson approach), and the lesion was totally removed. The tumor measured 8.0 *
      4.3 * 3.7 cm and microscopically appeared as a schwannoma composed of interwoven
      bundles of elongated cells (Antoni A regions) mixed with less cellular regions
      (Antoni B). Immunohistochemical study stained intensively for vimentin and S-100.
      Conclusion Schwannomas of the olfactory groove are extremely rare, and the
      findings of origin of this tumor is still uncertain but recent studies point most
      probably to the meningeal branches of trigeminal nerve or anterior ethmoidal
      nerves. 

PMID- 25992161
TI  - Research awards 2015.

PMID- 25992160
TI  - Nasolacrimal duct mucocele: case report and literature review.
AB  - Introduction Mucoceles are benign expansive cystic formations, composed of a
      mucus-secreting epithelium (respiratory or pseudostratified epithelium).
      Nasolacrimal mucocele occurs in a small proportion of children with nasolacrimal
      duct obstruction and is characterized by a cystic mass in the medial canthus with
      dilation of the nasolacrimal duct; although dacryocystoceles are rare in adults,
      they have been reported in patients with trachoma. Objective Discuss clinical
      aspects, diagnosis, and therapeutic management of mucocele of nasolacrimal duct
      based on literature review. Resumed Report The authors report a case of bilateral
      congenital nasolacrimal duct cysts in a 30-year-old man, identified as a tumor in
      the topography of both lacrimal sacs since birth without associated symptoms. The
      patient underwent successive surgical treatments, leading to recurrence of the
      tumor at the right side and recurrent local infections. Conclusion Endoscopic
      dacryocystorhinostomy has been increasingly used with good results and success
      rates similar to the external access. 

PMID- 25992162
TI  - Comparing voice self-assessment with auditory perceptual analysis in patients
      with multiple sclerosis.
AB  - Introduction Disordered voice quality could be a symptom of multiple sclerosis
      (MS). The impact of MS on voice-related quality of life is still controversial.
      Objectives The aim of this study was to compare the results of voice self
      assessment with the results of expert perceptual assessment in patients with MS.
      Methods The research included 38 patients with relapse-remitting MS (23 women and
      15 men; ages 21 to 83, mean = 44). All participants filled out a Voice Handicap
      Index (VHI), and their voice sample was analyzed by speech and language
      professionals using the Grade Roughness Breathiness Asthenia Strain scale
      (GRBAS). Results The patients with MS had significantly higher VHI than control
      group participants (mean value 16.68 +/- 16.2 compared with 5.29 +/- 5.5, p =
      0.0001). The study established a notable level of dysphonia in 55%, roughness and
      breathiness in 66%, asthenia in 34%, and strain in 55% of the vocal samples. A
      significant correlation was established between VHI and GRBAS scores (r = 0.3693,
      p = 0.0225), and VHI and asthenia and strain components (r = 0.4037 and 0.3775, p
      = 0.012 and 0.0195, respectively). The female group showed positive and
      significant correlation between claims for self-assessing one's voice (pVHI) and
      overall GRBAS scores, and between pVHI and grade, roughness, asthenia, and strain
      components. No significant correlation was found for male patients (p > 0.05).
      Conclusion A significant number of patients with MS experienced voice problems.
      The VHI is a good and effective tool to assess patient self-perception of voice
      quality, but it may not reflect the severity of dysphonia as perceived by voice
      and speech professionals. 

PMID- 25992163
TI  - Teleducation about Cleft Lip and Palate: An Interdisciplinary Approach in the
      Promotion of Health.
AB  - Introduction The Young Doctor Project (YDP) uses Telehealth and Interactive
      Teleducation instruments to promote the integration of different areas of health
      and to build knowledge. This methodology can also foster public awareness on
      various issues related to health. In this context, the objective of this study
      was to emphasize cleft lip and palate (CLP), which is one of the most common
      birth defects in Brazil. Objective The study aimed to apply a model of education
      regarding CLP, based on the dynamics of the YDP, and to evaluate the
      participants' knowledge acquired after participating in the YDP. Methods The
      participants were 41 students, 13 to 15 years of age and at the eight- and ninth
      grade levels in a private elementary school in Bauru (Brazil). To analyze the
      performance of the participants, a questionnaire was administered before and
      after the completion of the training program. The training program was structured
      in three steps using: (1) interactive teleducation classes, (2) a cybertutor, and
      (3) practical activities. Results There was a statistically significant
      difference between the pre- and postparticipation questionnaire results. The
      improved performance of participants is evidenced by the increase in the rate of
      correct answers on all issues. Conclusion The YDP on CLP was applied in the
      school setting following the three steps recommended by the project, and, after
      the implementation of the training program, there was a significant increase in
      participants' knowledge of CLP. The YDP on CLP proved an effective tool in
      promoting health education. 

PMID- 25992164
TI  - Parotid incidentaloma identified by positron emission/computed tomography: when
      to consider diagnoses other than warthin tumor.
AB  - Introduction Parotid gland incidentalomas (PGIs) are unexpected hypermetabolic
      foci in the parotid region that can be found when scanning with whole-body
      positron emission/computed tomography (PET/CT). These deposits are most commonly
      due to benign lesions such as Warthin tumor. Objective The aim of this study was
      to determine the prevalence of PGIs identified in PET/CT scans and to assess the
      role of smoking in their etiology. Methods We retrospectively reviewed all PET/CT
      scans performed at our center in search of PGIs and identified smoking status and
      standardized uptake value (SUVmax) in each case. We also analyzed the database of
      parotidectomies performed in our department in the previous 10 years and focused
      on the pathologic diagnosis and the presence or absence of smoking in each case.
      Results Sixteen cases of PGIs were found in 4,250 PET/CT scans, accounting for
      0.4%. The average SUVmax was 6.5 (range 2.8 to 16). Cytology was performed in
      five patients; it was benign in four cases and inconclusive in one case. Thirteen
      patients had a history of smoking. Of the parotidectomies performed in our center
      with a diagnosis of Warthin tumor, we identified a history of smoking in 93.8% of
      those patients. Conclusions The prevalence of PGIs on PET/CT was similar to that
      reported by other authors. Warthin tumor is frequently diagnosed among PGIs on
      PET/CT, and it has a strong relationship with smoking. We suggest that a
      diagnosis other than Warthin tumor should be considered for PGIs in nonsmokers. 

PMID- 25992165
TI  - Preoperative imaging modalities to predict the risk of regional nodal recurrence
      in well-differentiated thyroid cancers.
AB  - Introduction Thyroid cancer incidence has increased in the previous 2 decades.
      Preoperative identification of lymph node metastasis is a suggested risk factor
      associated with recurrence following thyroidectomy. Objectives We aimed to
      evaluate the accuracy of preoperative radiologic investigations of nodal status
      in determining the postoperative risk of regional nodal recurrence in cases of
      well-differentiated thyroid cancer. Methods This is a case series. We
      retrospectively reviewed data, including preoperative ultrasonography and/or
      computed tomography results, on patients who underwent total thyroidectomy for
      thyroid cancer at our hospital between 2006 and 2012. Prognostic factors for
      predicting recurrence, including age, sex, tumor diameter, and nodal diameter,
      were evaluated. Results Total thyroidectomy was performed on 24 male and 74
      female patients (median age, 43 years). The median follow-up time was 21 months.
      Sixty-eight patients had papillary thyroid cancer, and 30 had follicular cancer.
      Nodal recurrence was evident in 30% of patients, and 4% of patients died.
      Identification of lymph node involvement during preoperative radiologic
      investigations was strongly prognostic for recurrence: 35.3% of patients with
      positive preoperative ultrasonography findings and 62.5% of those with positive
      preoperative computed tomography findings had recurrence (p = 0.01). Conclusions
      Preoperative identification of lymph node metastasis on radiologic studies was
      correlated with an increased risk of regional nodal recurrence in well
      differentiated thyroid cancer. Computed tomography was superior to
      ultrasonography in detecting metastatic nodal involvement preoperatively and is
      therefore recommended for preoperative assessment and postoperative follow-up. 

PMID- 25992166
TI  - Foreign bodies in the ear, nose and throat: an experience in a tertiary care
      hospital in central Nepal.
AB  - Introduction A foreign body (FB) is an object or substance foreign to the
      location where it is found. FBs in the ear, nose, and throat are a common problem
      frequently encountered in both children and adults. Objective To analyze FBs in
      terms of type, site, age, and gender distribution and method of removal. Methods
      A retrospective study was performed in a tertiary care hospital in the central
      part of Nepal. The study period was from June 2013 to May 2014. The information
      was obtained from hospital record books. Results A total of 134 patients had FBs
      in the ear, nose, or throat; 94 were males and 40 were females. Of the 134
      patients, 70 (52.23%) had FB in the ear, 28 (20.89%) in the nose, and 36 (26.86%)
      in the throat. The FB was animate (living) in 28 (40%) patients with FB in the
      ear and 1 (3.5%) patient with FB in the nose, but the FB was inanimate
      (nonliving) in any patient with FB in the throat, in 42 (60%) patients with FB in
      the ear FB, and in 27 (96.4%) patients with FB of the nose. The FB was removed
      with or without local anaesthesia (LA) in 98 (73.13%) patients, and only 36
      patients (26.86%) required general anaesthesia (GA). The most common age group
      affected was <10 years. Conclusion FBs in the ear and nose were found more
      frequently in children, and the throat was the most common site of FB in adults
      and elderly people. Most of the FBs can be easily removed in emergency room or
      outpatient department. 

PMID- 25992167
TI  - Differential diagnosis and treatment of isolated pathologies of the sphenoid
      sinus: retrospective study of 46 cases.
AB  - Introduction Isolated disease of the sphenoid is rare and has often been
      overlooked due to its remote location and difficult access. Objective A
      retrospective study of the main causes of isolated sphenoid sinus diseases with
      discussion of the most appropriate methods of diagnosis and treatment. Methods A
      total of 46 cases of isolated sphenoid disease treated between January 2008 and
      December 2013 were evaluated by objective ear, nose, and throat examination and
      video endoscopy, computed tomography of the paranasal sinuses, and, in some
      cases, magnetic resonance imaging. In each case, we decided between drug and/or
      endoscopic treatment. Results We identified 12 cases of isolated sphenoiditis
      (26.1%), 3 cases of fungal sphenoiditis (6.5%), 3 cases of sphenochoanal polyps
      (6.5%), 22 cases of mucocele (47.8%), 2 cases of cerebrospinal fluid leak (4.3%),
      and 1 case each of meningoencephalocele (2.1%), inverted papilloma (2.1%),
      fibrous dysplasia (2.1%), and squamous cell carcinoma (2.1%). Conclusion A
      prevalence of inflammatory and infectious diseases was found, and endoscopic
      surgery for the sphenoid sinus approach is effective in treating various diseases
      of the isolated sphenoid, whether complicated or not. 

PMID- 25992168
TI  - Surfactant protein a expression in chronic rhinosinusitis and atrophic rhinitis.
AB  - Introduction Surfactant protein A (SP-A) exhibits antimicrobial properties and
      interacts with a variety of respiratory tract pathogens. Objective The objective
      of this study was to detect the presence of SP-A and measure its alterations in
      chronic rhinosinusitis (CRS) and primary atrophic rhinitis (PAR) versus healthy
      controls. Methods Inferior turbinate and sinus mucosal biopsies were taken from
      30 patients with CRS, 30 patients with PAR, and 20 healthy controls.
      Immunohistochemical staining for SP-A and polymerase chain reaction (PCR)
      amplification of SP-A messenger RNA were performed on nasal tissue samples.
      Results Immunostaining localized SP-A to the mucosa and submucosal glands in CRS
      specimens but failed to localize it in PAR specimens. Quantitative PCR showed a
      high, statistically significant increase in the SP-A levels of patients with CRS
      when compared with controls (p < 0.0001) and also demonstrated a significant
      reduction of SP-A in patients with PAR compared with controls (p < 0.005).
      Conclusion SP-A is significantly increased in CRS and decreased significantly in
      PAR and appears to be expressed by respiratory epithelial cells and submucosal
      glandular elements of the sinonasal mucosa. The potential therapeutic
      applications of surfactant in the enhancement of mucociliary clearance need to be
      studied. 

PMID- 25992169
TI  - Mercury exposure in a riverside Amazon population, Brazil: a study of the
      ototoxicity of methylmercury.
AB  - Introduction Mercury poisoning causes hearing loss in humans and animals. Acute
      and long-term exposures produce irreversible peripheral and central auditory
      system damage, and mercury in its various forms of presentation in the
      environment is ototoxic. Objective We investigated the otoacoustic emissions
      responses in a riverside population exposed to environmental mercury by analyzing
      the inhibitory effect of the medial olivocochlear system (MOCS) on transient
      otoacoustic emissions (TEOAE). Methods The purpose of the research was to
      evaluate the entire community independently of variables of sex and age. All of
      the participants were born and lived in a riverside community. After
      otolaryngologic evaluation, participants were received tympanometry, evaluation
      of contralateral acoustic reflexes, pure tone audiometry, and recording of TEOAEs
      with nonlinear click stimulation. Hair samples were collect to measure mercury
      levels. Results There was no significant correlation between the inhibitory
      effect of the MOCS, age, and the level of mercury in the hair. Conclusions The
      pathophysiological effects of chronic exposure may be subtle and nonspecific and
      can have a long period of latency; therefore, it will be important to monitor the
      effects of mercury exposure in the central auditory system of the Amazon
      population over time. Longitudinal studies should be performed to determine
      whether the inhibitory effect of the MOCS on otoacoustic emissions can be an
      evaluation method and diagnostic tool in populations exposed to mercury. 

PMID- 25992170
TI  - Lipidomic profiling of mastoid bone and tissue from patients with chronic
      otomastoiditis.
AB  - Introduction Chronic otomastoiditis causes pain, otorrhea, and hearing loss
      resulting from the growth of tissue within the normally hollow mastoid cavity.
      Objectives In this report, we used a lipidomics approach to profile major mastoid
      bone and tissue lipids from patients with and without otomastoiditis. Methods The
      bone dust created during mastoidectomy, as well as the mastoid tissue, was
      analyzed from seven patients. Bone dust was also collected and analyzed in an
      additional four otologic cases (parotidectomy requiring mastoidectomy). Samples
      were subjected to a modified Bligh/Dyer lipid extraction, then high-performance
      thin-layer chromatography (HPTLC), combined gas chromatography/electron impact
      mass spectrometry (GC/EI-MS), and flow-injection/electrospray ionization-tandem
      mass spectrometry (FI/ESI-MSMS). Data were analyzed for identification and
      profiling of major lipid components. Results HPTLC revealed the presence of
      various lipid classes, including phosphatidylcholines, cholesterol, and
      triacylglycerols. GC/EI-MS analysis revealed the presence of cholesterol and
      several fatty acids. FI/ESI-MSMS analysis revealed a host of
      phosphatidylcholines, phosphatidylethanolamines, and cholesteryl esters.
      Conclusion We used a lipidomics approach to develop an efficient (both in time
      and tissue amount) methodology for analysis of these tissues, identify the most
      abundant and common lipid species, and create a base of knowledge from which more
      focused endeavors in biomarker discovery can emerge. In an effort toward improved
      patient categorization and individualized intervention, the ultimate goal of this
      work is to correlate these lipid molecules to disease state and progression. This
      is the first reported study of its kind on these tissues. 

PMID- 25992171
TI  - Auditory neuropathy/dyssynchrony: a retrospective analysis of 15 cases.
AB  - Introduction Auditory neuropathy/dyssynchrony (AN/AD) comprises a spectrum of
      pathology affecting the auditory pathways anywhere from the inner hair cells to
      the brainstem. It is characterized by an absent or atypical auditory brainstem
      response (ABR) with preservation of the cochlear microphonics and/or otoacoustic
      emissions (OAEs). Objective Retrospective analysis of patients with AN/AD.
      Methods Fifteen patients with AN/AD were included in this study and their records
      were retrospectively investigated. Results Possible etiology of AN/AD was
      neonatal hyperbilirubinemia in three patients, family history of hearing loss in
      three patients, consanguineous marriage in two patients, head trauma in two
      patients, mental motor retardation in one patient, cerebrovascular disease in one
      patient, and there was no apparent cause in three patients. Conclusion
      Otolaryngologists should keep in mind the diagnosis of AN/AD especially in
      patients complaining of difficulty in hearing and speech and audiological
      evidence of disassociation between pure tone and speech audiometry. ABR and OAE
      testing is recommended in these patients for AN/AD diagnosis. 

PMID- 25992172
TI  - Characterization of hearing thresholds from 500 to 16,000 hz in dentists: a
      comparative study.
AB  - Introduction High-level noise exposure in dentists' workplaces may cause damages
      to the auditory systems. High-frequency audiometry is an important tool in the
      investigation in the early diagnosis of hearing loss. Objectives To analyze the
      auditory thresholds at frequencies from 500 to 16,000 Hz of dentists in the city
      of Curitiba. Methods This historic cohort study retrospectively tested hearing
      thresholds from 500 to 16,000 Hz with a group of dentists from Curitiba, in the
      state of Parana, Brazil. Eighty subjects participated in the study, separated
      into a dentist group and a control group, with the same age range and gender
      across groups but with no history of occupational exposure to high levels of
      sound pressure in the control group. Subjects were tested with conventional
      audiometry and high-frequency audiometry and answered a questionnaire about
      exposure to noise. Results Results showed that 81% of dentists did not receive
      any information regarding noise at university; 6 (15%) dentists had sensorineural
      hearing impairment; significant differences were observed between the groups only
      at frequencies of 500 Hz and 1,000, 6,000 and 8,000 Hz in the right ear. There
      was no significant difference between the groups after analysis of mean hearing
      thresholds of high frequencies with the average hearing thresholds in
      conventional frequencies; subjects who had been working as dentists for longer
      than 10 years had worse tonal hearing thresholds at high frequencies. Conclusions
      In this study, we observed that dentists are at risk for the development of
      sensorineural hearing loss especially after 10 years of service. 

PMID- 25992173
TI  - Auditory brainstem response in term and preterm infants with neonatal
      complications: the importance of the sequential evaluation.
AB  - Introduction Literature data are not conclusive as to the influence of neonatal
      complications in the maturational process of the auditory system observed by
      auditory brainstem response (ABR) in infants at term and preterm. Objectives
      Check the real influence of the neonatal complications in infants by the
      sequential auditory evaluation. Methods Historical cohort study in a tertiary
      referral center. A total of 114 neonates met inclusion criteria: treatment at the
      Universal Neonatal Hearing Screening Program of the local hospital; at least one
      risk indicator for hearing loss; presence in both evaluations (the first one
      after hospital discharge from the neonatal unit and the second one at 6 months
      old); all latencies in ABR and transient otoacoustic emissions present in both
      ears. Results The complications that most influenced the ABR findings were Apgar
      scores less than 6 at 5 minutes, gestational age, intensive care unit stay, peri
      intraventricular hemorrhage, and mechanical ventilation. Conclusion Sequential
      auditory evaluation is necessary in premature and term newborns with risk
      indicators for hearing loss to correctly identify injuries in the auditory
      pathway. 

PMID- 25992174
TI  - Health promotion in obstructive sleep apnea syndrome.
AB  - Introduction Obstructive sleep apnea syndrome (OSAS), which is commonly
      underdiagnosed, has a high occurrence in the world population. Health education
      concerning sleep disorders and OSAS should be implemented. Objectives The
      objective was to identify studies related to preventive actions on sleep
      disorders, with emphasis on OSAS. Data Synthesis A literature review was
      conducted using Lilacs, Medline, PubMed, and Scopus by combining the following
      keywords: "Health Promotion," "Sleep Disorders," "Primary Prevention," "Health
      Education," and "Obstructive Sleep Apnea Syndromes." Initially, 1,055 papers,
      from 1968 to 2013, were located, with the majority from the Scopus database. The
      inclusion criteria were applied, and four articles published between 2006 and
      2012 were included in the present study. Conclusions The studies on preventive
      actions in sleep disorders, with emphasis on OSAS, involved the general
      population and professionals and students in the health field and led to
      increased knowledge on sleep disorders and more appropriate practices. 

PMID- 25992175
TI  - The study of otoacoustic emissions and the suppression of otoacoustic emissions
      in subjects with tinnitus and normal hearing: an insight to tinnitus etiology.
AB  - Introduction Analysis of the suppression effect is a simple method to evaluate
      cochlear status and central auditory mechanisms and, more specifically, the
      medial olivocochlear system. This structure may be involved in the generation of
      mechanisms that cause tinnitus and in the pathophysiology of tinnitus in patients
      with tinnitus and normal hearing. Objective To review the literature of the
      etiology of tinnitus on the lights of otoacoustic emissions in patients with
      normal hearing. Data Synthesis Individuals with tinnitus and normal hearing have
      a higher prevalence of alterations in transient-evoked otoacoustic emissions and
      distortion-product otoacoustic emissions than normal subjects. This fact suggests
      that dysfunctions of the outer hair cells (OHCs) might be important in the
      generation of the tinnitus; however, this feature is not always present in those
      who have the symptoms of tinnitus. Final Comments These findings suggest that OHC
      dysfunction is not necessary for tinnitus development-that is, there might be
      mechanisms other than OHC damage in the tinnitus development. On the other hand,
      OHC dysfunction alone is not sufficient to cause the symptom, because a great
      many individuals with OHC dysfunction did not complain about tinnitus. 

PMID- 25992177
TI  - Ortner's Syndrome: Secondary Laryngeal Paralysis Caused by a Great Thoracic Aorta
      Aneurysm.
AB  - Introduction Recurrent laryngeal nerve injury caused by cardiovascular disease is
      a rare condition, and often it is the only prominent sign of an imminent break of
      an aortic artery aneurysm. Objective To report left laryngeal paralysis caused by
      a great aortic arch aneurysm and to highlight the importance of an
      otorhinolaryngologic evaluation along with a thoracic radiologic study. Resumed
      Report A 42-year-old man complained of thickness of his voice and dysphagia for 3
      months, but no thoracic pain or other relevant complaints. Video laryngoscopy
      revealed immobility of his left vocal fold in the paramedian position. Imaging
      was obtained for investigation, including magnetic resonance imaging of his
      thorax, which showed a fusiform aneurysm in the aortic arch, leading to recurrent
      compression of the left laryngeal nerve. The patient was successfully treated
      with endovascular repair of the aneurysm. At 2-month follow-up, there was still
      no recovery of the laryngeal mobility. Conclusion An aortic artery aneurysm can
      suddenly break, requiring emergency heart surgery, and the results can be fatal
      in many cases. We suggest routine exam of the vocal folds in all patients with a
      heart condition, and we review the literature and suggest the use of imaging to
      reduce the number of emergency procedures. 

PMID- 25992176
TI  - Olfaction in neurologic and neurodegenerative diseases: a literature review.
AB  - Introduction Loss of smell is involved in various neurologic and
      neurodegenerative diseases, such as Parkinson disease and Alzheimer disease.
      However, the olfactory test is usually neglected by physicians at large.
      Objective The aim of this study was to review the current literature about the
      relationship between olfactory dysfunction and neurologic and neurodegenerative
      diseases. Data Synthesis Twenty-seven studies were selected for analysis, and the
      olfactory system, olfaction, and the association between the olfactory
      dysfunction and dementias were reviewed. Furthermore, is described an up to date
      in olfaction. Conclusion Otolaryngologist should remember the importance of
      olfaction evaluation in daily practice. Furthermore, neurologists and physicians
      in general should include olfactory tests in the screening of those at higher
      risk of dementia. 

PMID- 25992178
TI  - Intralabyrinthine penetrating ventilation tube with preservation of hearing: an
      unusual clinical situation.
AB  - Introduction Traumatic perilymphatic fistula is not a rare event with regards to
      sport activities or traffic accident. However, iatrogenic damage to the inner ear
      can occur following the common use of grommets and ventilation tube insertion.
      Objectives To report an unusual case of insertion of aeration tube into the
      vestibule trough the stapes footplate. Resumed Report A 62-year-old woman
      experienced iatrogenic penetration into the vestibule from a ventilation tube
      inserted for retraction pocket management. The event was misdiagnosed both by the
      surgeon and by the emergency room physicians, leading to delay in the management.
      However, preservation of the hearing function lasted for 2 weeks prior to
      deafness, thanks to the valve of Bast, which preserved the cochlear fluid.
      Conclusion This case gives us the opportunity to stress the need for systematic
      clinical examination of traumatic injury to the ear and to recommend performing
      multiplanar millimetric computed tomography scan with accurate interpretation.
      Traumatic injuries should be referred to a dedicated traumatic emergency referral
      center. 

PMID- 25992179
TI  - A rare location of angiofibroma in the inferior turbinate in young woman.
AB  - Introduction Juvenile nasopharyngeal angiofibroma is a rare benign neoplasm in
      the nasopharynx. The tumor tends to be locally aggressive and is typically seen
      in adolescent boys. Extranasopharyngeal angiofibromas have been reported
      sporadically in the literature. They most commonly originate from the maxillary
      sinus. Objectives A 26-year-old woman was referred to our clinic with
      intermittent epistaxis from the right nasal passage for the previous 2 months.
      Maxillofacial magnetic resonance imaging showed a lobular, contoured mass
      originating from the right inferior turbinate and hanging in the right nasal
      cavity, with dense contrast enhancement denoting hypervascularity. Resumed Report
      Vascular feeding of the mass was seen from the right internal maxillary artery
      with angiography, and this branch was embolized. On the following day, the
      patient underwent transnasal endoscopic excision of the mass. An approximately 3
      cm-diameter mass was excised by partial turbinectomy, and the posterior edge of
      the remaining turbinate was cauterized. Conclusion Extranasopharyngeal
      angiofibromas are rarely seen, and the inferior turbinate is an extremely rare
      location for them. This young woman is the first case reported in the English
      literature of angiofibroma originating from the inferior turbinate. We should
      consider these neoplasms can be found in female, nonadolescent patients with
      extranasopharyngeal localization, and we should not perform biopsy because of its
      massive bleeding. 

PMID- 25992180
TI  - Acute specialized care of patients with ebola virus disease: gaps and
      opportunities.

PMID- 25992181
TI  - Neurological surgery in Guinea, west Africa.

PMID- 25992182
TI  - High survival rates and associated factors among ebola virus disease patients
      hospitalized at donka national hospital, conakry, Guinea.
AB  - BACKGROUND: Anecdotal reports suggesting that survival rates among hospitalized
      patients with Ebola virus disease in Guinea are higher than the 29.2% rate
      observed in the current epidemic in West Africa. METHODS: Survival after symptom
      onset was determined using Kaplan Meier survival methods among patients with
      confirmed Ebola virus disease treated in Conakry, Guinea from March 25, 2014, to
      August 5, 2014. We analyzed the relationship between survival and patient
      factors, including demographics and clinical features. RESULTS: Of the 70
      patients analyzed [mean age +/- standard deviation (SD), 34 +/- 14.1; 44 were
      men], 42 were discharged alive with a survival rate among hospitalized patients
      of 60% (95% confidence interval, 41.5-78.5%). The survival rate was 28 (71.8%)
      among 39 patients under 34 years of age, and 14 (46.7%) among 30 patients aged 35
      years or greater (p = 0.034). The rates of myalgia (3 of 42 versus 7 of 28, p =
      0.036) and hiccups (1 of 42 versus 5 of 28, p = 0.023) were significantly lower
      among patients who survived. CONCLUSIONS: Our results provide insights into a
      cohort of hospitalized patients with Ebola virus disease in whom survival is
      prominently higher than seen in other cohorts of hospitalized patients.

PMID- 25992183
TI  - Use of Clostridium botulinum toxin in gastrointestinal motility disorders in
      children.
AB  - More than a century has elapsed since the identification of Clostridia
      neurotoxins as the cause of paralytic diseases. Clostridium botulinum is a
      heterogeneous group of Gram-positive, rod-shaped, spore-forming, obligate
      anaerobic bacteria that produce a potent neurotoxin. Eight different Clostridium
      botulinum neurotoxins have been described (A-H) and 5 of those cause disease in
      humans. These toxins cause paralysis by blocking the presynaptic release of
      acetylcholine at the neuromuscular junction. Advantage can be taken of this
      blockade to alleviate muscle spams due to excessive neural activity of central
      origin or to weaken a muscle for treatment purposes. In therapeutic applications,
      minute quantities of botulinum neurotoxin type A are injected directly into
      selected muscles. The Food and Drug Administration first approved botulinum toxin
      (BT) type A in 1989 for the treatment of strabismus and blepharospasm associated
      with dystonia in patients 12 years of age or older. Ever since, therapeutic
      applications of BT have expanded to other systems, including the gastrointestinal
      tract. Although only a single fatality has been reported to our knowledge with
      use of BT for gastroenterological conditions, there are significant complications
      ranging from minor pain, rash and allergic reactions to pneumothorax, bowel
      perforation and significant paralysis of tissues surrounding the injection
      (including vocal cord paralysis and dysphagia). This editorial describes the
      clinical experience and evidence for the use BT in gastrointestinal motility
      disorders in children. 

PMID- 25992184
TI  - Risk factors affecting the Barrett's metaplasia-dysplasia-neoplasia sequence.
AB  - Esophageal adenocarcinoma has the fastest growing incidence rate of any cancer in
      the United States, and currently carries a very poor prognosis with 5 years
      relative survival rates of less than 15%. Current curative treatment options are
      limited to esophagectomy, a procedure that suffers from high complication rates
      and high mortality rates. Metaplasia of the esophageal epithelium, a condition
      known as Barrett's esophagus (BE), is widely accepted as the precursor lesion for
      adenocarcinoma of the esophagus. Recently, radio-frequency ablation has been
      shown to be an effective method to treat BE, although there is disagreement as to
      whether radio-frequency ablation should be used to treat all patients with BE or
      whether treatment should be reserved for those at high risk for progressing to
      esophageal adenocarcinoma while continuing to endoscopically survey those with
      low risk. Recent research has been targeted towards identifying those at greater
      risk for progression to esophageal adenocarcinoma so that radio-frequency
      ablation therapy can be used in a more targeted manner, decreasing the total
      health care cost as well as improving patient outcomes. This review discusses the
      current state of the literature regarding risk factors for progression from BE
      through dysplasia to esophageal adenocarcinoma, as well as the current need for
      an integrated scoring tool or risk stratification system capable of
      differentiating those patients at highest risk of progression in order to target
      these endoluminal therapies. 

PMID- 25992185
TI  - Endoscopic management of post-liver transplant biliary complications.
AB  - Biliary complications are being increasingly encountered in post liver transplant
      patients because of increased volume of transplants and longer survival of these
      recipients. Overall management of these complications may be challenging, but
      with advances in endoscopic techniques, majority of such patients are being dealt
      with by endoscopists rather than the surgeons. Our review article discusses the
      recent advances in endoscopic tools and techniques that have proved endoscopic
      retrograde cholangiography with various interventions, like sphincterotomy, bile
      duct dilatation, and stent placement, to be the mainstay for management of most
      of these complications. We also discuss the management dilemmas in patients with
      surgically altered anatomy, where accessing the bile duct is challenging, and the
      recent strides towards making this prospect a reality. 

PMID- 25992186
TI  - Role of stenting in gastrointestinal benign and malignant diseases.
AB  - Advances in stents design have led to a substantial increase in the use of stents
      for a variety of digestive diseases. Initially developed as a non-surgical
      treatment for palliation of esophageal cancer, the stents now have an emerging
      role in the management of malignant and benign conditions as well as in all
      segments of the gastrointestinal tract. In this review, relevant literature
      search and expert opinions have been used to evaluate the key-role of stenting in
      gastrointestinal benign and malignant diseases. 

PMID- 25992188
TI  - Peroral endoscopic myotomy.
AB  - Peroral endoscopic myotomy (POEM) incorporates concepts of natural orifice
      translumenal endoscopic surgery and achieves endoscopic myotomy by utilizing a
      submucosal tunnel as an operating space. Although intended for the palliation of
      symptoms of achalasia, there is mounting data to suggest it is also efficacious
      in the management of spastic esophageal disorders. The technique requires an
      understanding of the pathophysiology of esophageal motility disorders as well as
      knowledge of surgical anatomy of the foregut. POEM achieves short term response
      in 82% to 100% of patients with minimal risk of adverse events. In addition, it
      appears to be effective and safe even at the extremes of age and regardless of
      prior therapy undertaken. Although infrequent, the ability of the endoscopist to
      manage an intraprocedural adverse event is critical as failure to do so could
      result in significant morbidity. The major late adverse event is gastroesophageal
      reflux which appears to occur in 20% to 46% of patients. Research is being
      conducted to clarify the optimal technique for POEM and a personalized approach
      by measuring intraprocedural esophagogastric junction distensibility appears
      promising. In addition to esophageal disorders, POEM is being studied in the
      management of gastroparesis (gastric pyloromyotomy) with initial reports
      demonstrating technical feasibility. Although POEM represents a paradigm shift
      the management of esophageal motility disorders, the results of prospective
      randomized controlled trials with long-term follow up are eagerly awaited. 

PMID- 25992189
TI  - Current status of peroral cholangioscopy in biliary tract diseases.
AB  - Peroral cholangioscopy (POC) is an important tool for the management of a
      selected group of biliary diseases. Because of its direct visualization, POC
      allows targeted diagnostic and therapeutic procedures. POC can be performed using
      a dedicated cholangioscope that is advanced through the accessory channel of a
      duodenoscope or via the insertion of a small-diameter endoscope directly into the
      bile duct. POC was first described in the 1970s, but the use of earlier
      generation devices was substantially limited by the cumbersome equipment setup
      and high repair costs. For nearly ten years, several technical improvements,
      including the single-operator system, high-quality images, the development of
      dedicated accessories and the increased size of the working channel, have led to
      increased diagnostic accuracy, thus assisting in the differentiation of benign
      and malignant intraductal lesions, targeting biopsies and the precise delineation
      of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult
      bile duct stones, ablative therapies for biliary malignancies and direct biliary
      drainage can be performed under POC control. Recent developments of new types of
      conventional POCs allow feasible, safe and effective procedures at reasonable
      costs. In the current review, we provide an updated overview of POC, focusing our
      attention on the main current clinical applications and on areas for future
      research. 

PMID- 25992187
TI  - Recent advancement of therapeutic endoscopy in the esophageal benign diseases.
AB  - Over the past 30 years, the field of endoscopy has witnessed several advances.
      With the advent of endoscopic mucosal resection, removal of large mucosal lesions
      have become possible. Thereafter, endoscopic submucosal resection was refined,
      permitting en bloc removal of large superficial neoplasms. Such techniques have
      facilitated the development of antireflux mucosectomy, a promising novel
      treatment for gastroesophageal reflux. The introduction and use of over the scope
      clips has allowed for endoscopic closure of defects in the gastrointestinal
      tract, which were traditionally treated with surgical intervention. With the
      development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and
      spastic disorders of the esophagus have been revolutionized. From the submucosal
      tunnelling technique developed for POEM, Per oral endoscopic tumor resection of
      subepithelial tumors was made possible. Simultaneously, advances in biotechnology
      have expanded esophageal stenting capabilities with the introduction of fully
      covered metal and plastic stents, as well as biodegradable stents. Once deemed a
      primarily diagnostic tool, endoscopy has quickly transcended to a minimally
      invasive intervention and therapeutic tool. These techniques are reviewed with
      regards to their application to benign disease of the esophagus. 

PMID- 25992190
TI  - Endoscopic management of bariatric complications: A review and update.
AB  - With over a third of Americans being considered obese, bariatric procedures have
      now become the most performed operation be general surgeons in the United States.
      The most common operations are the Laparoscopic Roux-en-Y Gastric Bypass, the
      Laparoscopic Sleeve Gastrectomy, and the Laparoscopic Adjustable Gastric Band.
      With over 340000 bariatric procedures preformed worldwide in 2011, the absolute
      number of complications related to these operations is also increasing.
      Complications, although few, can be life threatening. One of the most dreaded
      acute complication is the anastomotic/staple line leak. If left undiagnosed or
      untreated they can lead to sepsis, multi organ failure, and death. Smaller or
      contained leaks can develop into fistulas. Although most patients with an acute
      anastomotic leak return to the operating room, there has been a trend to manage
      the stable patient with an endoscopic stent. They offer an advantage by creating
      a barrier between enteric content and the leak, and will allow the patients to
      resume enteral feeding much earlier. Fistulas are a complex and chronic
      complication with high morbidity and mortality. Postoperative bleeding although
      rare may also be treated locally with endoscopy. Stenosis is a more frequent late
      complication and is best-managed with endoscopic therapy. Stents may not heal
      every fistula or stenosis, however they may prevent certain patients the need for
      additional revisional surgery. 

PMID- 25992191
TI  - Endoscopic submucosal dissection in early gastric cancer in elderly patients and
      comorbid conditions.
AB  - The prognosis of early gastric cancer (EGC) is good if there is no concomitant
      lymph node metastasis. Therefore, the early detection of EGC is important to
      improve the prognosis of patients with gastric cancer. In Japan, 40% to 50% of
      all gastric cancers are EGC, and endoscopic submucosal dissection (ESD) is widely
      accepted as a local treatment for these lesions, particularly for large lesions
      that at one time were an indication for gastrectomy because of the difficulty of
      en-bloc resection. Consequently, this procedure can preserve the entire stomach
      and the patient's postoperative quality of life. ESD has become a general
      technique with improved procedures and devices, and has become the preferred
      treatment for EGC rather than gastrectomy. Therefore, ESD may demonstrate many
      advantages in patients who have several comorbidities, particularly elderly
      population, patients taking antithrombotic agents, or patients with chronic
      kidney disease, or liver cirrhosis. However, it is not yet clear whether patients
      with both EGC and comorbidities are feasible candidates for ESD and whether they
      would consequently be able to achieve a survival benefit after ESD. In this
      review, we discuss the clinical problems of ESD in patients with EGC and those
      comorbid conditions. 

PMID- 25992192
TI  - Is it time to replace propranolol with carvedilol for portal hypertension?
AB  - Beta-adrenergic receptor antagonists (beta-blockers) have been well established
      for use in portal hypertension for more than three decades. Different Non
      selective beta-blockers like propranolol, nadolol, timolol, atenolol, metoprolol
      and carvedilol have been in clinical practice in patients with cirrhosis.
      Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor
      blocker in trials conducted testing its efficacy for heart failure. Whether the
      same effect extends to its potency in the reduction of portal venous pressures is
      a topic of on-going debate. The aim of this review is to compare the hemodynamic
      and clinical effects of carvedilol with propranolol, and attempt assess whether
      carvedilol can be used instead of propranolol in patients with cirrhosis.
      Carvedilol is a promising agent among the beta blockers of recent time that has
      shown significant effects in portal hypertension hemodynamics. It has also
      demonstrated an effective profile in its clinical application specifically for
      the prevention of variceal bleeding. Carvedilol has more potent desired
      physiological effects when compared to Propranolol. However, it is uncertain at
      the present juncture whether the improvement in hemodynamics also translates into
      a decreased rate of disease progression and complications when compared to
      propranolol. Currently Carvedilol shows promise as a therapy for portal
      hypertension but more clinical trials need to be carried out before we can
      consider it as a superior option and a replacement for propranolol. 

PMID- 25992193
TI  - Tripartite comparison of single-incision and conventional laparoscopy in
      cholecystectomy: A multicenter trial.
AB  - AIM: To compare the characteristics of two single-incision methods, and
      conventional laparoscopy in cholecystectomy, and demonstrate the safety and
      feasibility. METHODS: Three hundred patients with gallstones or gallbladder
      polyps were admitted to two clinical centers from January 2013 to January 2014
      and were randomized into three groups of 100: single-incision three-device group,
      X-Cone group, and conventional group. The operative time, intraoperative blood
      loss, complications, postoperative pain, cosmetic score, length of
      hospitalization, and hospital costs were compared, with a follow-up duration of 1
      mo. RESULTS: A total of 142 males (47%) and 158 females (53%) were enrolled in
      this study. The population characteristics of these three groups is no
      significant differences exist in terms of age, sex, body mass index and American
      Society of Anesthesiology (P > 0.05). In results, there were no significant
      differences in blood loss, length of hospitalization, postoperative
      complications.The operative time in X-Cone group was significantly longer than
      other groups.There were significant differences in postoperative pain scores and
      cosmetic scores at diffent times after surgery (P < 0.05). CONCLUSION: This study
      shows that this two single-incision methods are safe and feasible. Both methods
      are superior to the conventional procedure in cosmetic and pain scores.

PMID- 25992194
TI  - Biliary leakage after urgent cholecystectomy: Optimization of endoscopic
      treatment.
AB  - AIM: To investigate the results of endoscopic treatment of postoperative biliary
      leakage occurring after urgent cholecystectomy with a long-term follow-up.
      METHODS: This is an observational database study conducted in a tertiary care
      center. All consecutive patients who underwent endoscopic retrograde
      cholangiography (ERC) for presumed postoperative biliary leakage after urgent
      cholecystectomy in the period between April 2008 and April 2013 were considered
      for this study. Patients with bile duct transection and biliary strictures were
      excluded. Biliary leakage was suspected in the case of bile appearance from
      either percutaneous drainage of abdominal collection or abdominal drain placed at
      the time of cholecystectomy. Procedural and main clinical characteristics of all
      consecutive patients with postoperative biliary leakage after urgent
      cholecystectomy, such as indication for cholecystectomy, etiology and type of
      leakage, ERC findings and post-ERC complications, were collected from our
      electronic database. All patients in whom the leakage was successfully treated
      endoscopically were followed-up after they were discharged from the hospital and
      the main clinical characteristics, laboratory data and common bile duct diameter
      were electronically recorded. RESULTS: During a five-year period, biliary leakage
      was recognized in 2.2% of patients who underwent urgent cholecystectomy. The
      median time from cholecystectomy to ERC was 6 d (interquartile range, 4-11 d).
      Endoscopic interventions to manage biliary leakage included biliary stent
      insertion with or without biliary sphincterotomy. In 23 (77%) patients after
      first endoscopic treatment bile flow through existing surgical drain ceased
      within 11 d following biliary therapeutic endoscopy (median, 4 d; interquartile
      range, 2-8 d). In those patients repeat ERC was not performed and the biliary
      stent was removed on gastroscopy. In seven (23%) patients repeat ERC was done
      within one to fourth week after their first ERC, depending on the extent of the
      biliary leakage. In two of those patients common bile duct stone was recognized
      and removed. Three of those seven patients had more complicated clinical course
      and they were referred to surgery and were excluded from long-term follow-up. The
      median interval from endoscopic placement of biliary stent to demonstration of
      resolution of bile leakage for ERC treated patients was 32 d (interquartile
      range, 28-43 d). Among the patients included in the follow-up (median 30.5 mo,
      range 7-59 mo), four patients (14.8%) died of severe underlying comorbid
      illnesses. CONCLUSION: Our results demonstrate the great efficiency of the
      endoscopic therapy in the treatment of the patients with biliary leakage after
      urgent cholecystectomy.

PMID- 25992195
TI  - Polyp detection rates using magnification with narrow band imaging and white
      light.
AB  - AIM: To compare the yield of adenomas between narrow band imaging and white light
      when using high definition/magnification. METHODS: This prospective, non
      randomized comparative study was performed at the endoscopy unit of veteran
      affairs medical center in Phoenix, Arizona. Consecutive patients undergoing first
      average risk colorectal cancer screening colonoscopy were selected. Two
      experienced gastroenterologists performed all the procedures that were blinded to
      each other's findings. Demographic details were recorded. Data are presented as
      mean +/- SEM. Proportional data were compared using the chi(2) test and means
      were compared using the Student's t test. Tandem colonoscopy was performed in a
      sequential and segmental fashion using one of 3 strategies: white light followed
      by narrow band imaging [Group A: white light (WL) -> narrow band imaging (NBI)];
      narrow band imaging followed by white light (Group B: NBI -> WL) and, white light
      followed by white light (Group C: WL -> WL). Detection rate of missed polyps and
      adenomas were evaluated in all three groups. RESULTS: Three hundred patients were
      studied (100 in each Group). Although the total time for the colonoscopy was
      similar in the 3 groups (23.8 +/- 0.7, 22.2 +/- 0.5 and 24.1 +/- 0.7 min for
      Groups A, B and C, respectively), it reached statistical significance between
      Groups B and C (P < 0.05). The cecal intubation time in Groups B and C was longer
      than for Group A (6.5 +/- 0.4 min and 6.5 +/- 0.4 min vs 4.9 +/- 0.3 min; P <
      0.05). The withdrawal time for Groups A and C was longer than Group B (18.9 +/-
      0.7 min and 17.6 +/- 0.6 min vs 15.7 +/- 0.4 min; P < 0.05). Overall miss rate
      for polyps and adenomas detected in three groups during the second look was 18%
      and 17%, respectively (P = NS). Detection rate for polyps and adenomas after
      first look with white light was similar irrespective of the light used during the
      second look (WL -> WL: 13.7% for polyps, 12.6% for adenomas; WL -> NBI: 14.2% for
      polyps, 11.3% for adenomas). Miss rate of polyps and adenomas however was
      significantly higher when NBI was used first (29.3% and 30.3%, respectively; P <
      0.05). Most missed adenomas were <= 5 mm in size. There was only one advanced
      neoplasia (defined by size only) missed during the first look. CONCLUSION: Our
      data suggest that the tandem nature of the procedure rather than the optical
      techniques was associated with the detection of additional polyps' and adenomas.

PMID- 25992196
TI  - Chronic abdominal pain secondary to mesenteric panniculitis treated successfully
      with endoscopic ultrasonography-guided celiac plexus block: A case report.
AB  - Mesenteric panniculitis is a chronic illness that is characterized by fibrosing
      inflammation of the mesenteries that can lead to intractable abdominal pain. Pain
      control is a crucial component of the management plan. Most patients will improve
      with oral corticosteroids treatment, however, some patients will require a trial
      of other immunosuppressive agents, and a minority of patients will continue to
      have refractory disease. Endoscopic ultrasound guided celiac plexus block is used
      frequently to control abdominal pain in patients with pancreatic pathology. To
      our knowledge there are no case reports describing its use in mesenteric
      panniculitis patients with refractory abdominal pain. 

PMID- 25992197
TI  - Anaemia in Waldmann's disease: A rare presentation of a rare disease.
AB  - A 32-year-old female presented with 5-year history of iron deficiency anemia,
      marked pallor and edema of both lower limbs. Laboratory investigations including
      complete blood count, blood film, iron studies, lipid profile, ascitic fluid
      analysis, test of stool for occult blood and alpha 1 anti-trypsin. Upper, lower
      gastrointestinal (GIT) endoscopies, and enteroscopy were performed. Imaging
      techniques as abdominal ultrasonography and computed tomography were done.
      Echocardiography, lymph node biopsy and bone marrow examination were normal. The
      case was diagnosed as Waldmann's disease with protein losing enteropathy and
      recurrent GIT bleeding. Management started with low fat diet with medium chain
      triglyceride, octreotide 200 MUg twice a day, tranexamic acid and blood
      transfusion. Then, exploratory laparotomy with pathological examination of
      resected segment was done when recurrent GIT bleeding occurred and to excluded
      malignant transformation. 

PMID- 25992198
TI  - Unreported complication of Bravo pH capsule dislodged into the pyriform sinus.
AB  - We report an unexpected, previously unreported complication of Bravo pH capsule
      dislodgement. During Bravo pH testing of a 44-year-old man with gastroesophageal
      reflux disease, we were unable to endoscopically visualize the capsule attached
      to the esophageal wall after deployment. After multiple attempts to detect the
      capsule, it was visualized in the left pyriform sinus. As there was significant
      risk for pulmonary dislodgement, ENT and pulmonary physicians were immediately
      consulted to review options for safe removal. Ultimately, ENT successfully
      retrieved the capsule with a foreign body removal forceps. The Bravo pH test is
      generally a well-tolerated diagnostic tool used to confirm the presence of
      abnormal esophageal acid reflux. While few complications have been reported,
      technical difficulties can occur, including poor data reception, misplacement,
      and early dislodgement. Rarely, more serious complications can occur, ranging
      from esophageal wall trauma to capsule aspiration. Gastroenterologists performing
      this procedure should be aware of the low, but non-trivial, risk of
      complications. 

PMID- 25992199
TI  - Role of chemotherapy in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a unique malignant head and neck cancer with
      clinical, demographic, and geographic features distinct from other head and neck
      epithelial malignancies. Non-keratinizing, poorly differentiated, and
      undifferentiated WHO types 2 and 3 is the most common subtypes of NPC. NPC is
      also characterized by its relatively high sensitivity to radiation, so that in
      the last decades radiotherapy (RT) has been the cornerstone of treatment.
      However, in the majority of cases NPC is discovered at locally advanced stage.
      The results are disappointing when RT alone is offered. The 5-year survival rates
      have been reported to be about 34-52%. The poor prognosis for advanced NPC led to
      increasing interests in exploring the use of chemotherapy (CT). NPC has been
      considered to be not only radiosensitive but also chemo-sensitive and has shown
      high response rate to various chemotherapeutic agents. Certainly, the treatment
      strategies for NPC will continue to change and evolve as a better understanding
      is gained of the molecular and immune mechanisms that drive this disease. We
      reviewed the current literature focusing on the role of CT and new-targeted
      agents. 

PMID- 25992201
TI  - A role of active brown adipose tissue in cancer cachexia?
AB  - Until a few years ago, adult humans were not thought to have brown adipose tissue
      (BAT). Now, this is a rapidly evolving field of research with perspectives in
      metabolic syndromes such as obesity and new therapies targeting its bio-energetic
      pathways. White, brown and so-called brite adipose fat seem to be able to trans
      differentiate into each other, emphasizing the dynamic nature of fat tissue for
      metabolism. Human and animal data in cancer cachexia to date provide some
      evidence for BAT activation, but its quantitative impact on energy expenditure
      and weight loss is controversial. Prospective clinical studies can address the
      potential role of BAT in cancer cachexia using (18)F-fluoro- deoxyglucose
      positron emission tomography-computed tomography scanning, with careful
      consideration of co-factors such as diet, exposure to the cold, physical activity
      and body mass index, that all seem to act on BAT recruitment and activity. 

PMID- 25992202
TI  - Lymph node dissection for gastric cancer: a critical review.
AB  - Gastric cancer is one of the most common neoplasms and an important cause of
      cancer-related death worldwide. Efforts to reduce its high mortality rates are
      currently focused on multidisciplinary management. However, surgery remains a
      cornerstone in the management of patients with resectable disease. There is still
      some controversy as to the extent of lymph node dissection for potentially
      curable stomach cancer. Surgeons in eastern countries favor more extensive lymph
      node dissection, whereas those in the West favor less extensive dissection. Thus,
      extent of lymph node dissection remains one of the most hotly discussed aspects
      of gastric surgery, particularly because most stomach cancers are now often
      comprehensively treated by adding some perioperative chemotherapy or chemo
      radiation. We provide a critical review of lymph nodes dissection for gastric
      cancer with a particular focus on its benefits in a multimodal approach. 

PMID- 25992200
TI  - A review of penile metastasis.
AB  - Penile cancer as primary disease is relatively rare in developed countries. The
      penis is a rare site of metastases in spite of its rich vascularization.
      Approximately 500 cases have been reported in the literature; almost 70% of
      primary lesions are of pelvic origin (from genitourinary or recto-sigmoid primary
      tumors). We describe a case of penile metastasis from lung cancer. The rarity of
      the event prompted us to also explore related reviews and discuss the incidence,
      physiopathology, diagnosis and therapy of penile secondary cancer. 

PMID- 25992203
TI  - Janus kinase inhibitors: jackpot or potluck?
AB  - The reports of a unique mutation in the Janus kinase-2 gene (JAK2) in
      polycythemia vera by several independent groups in 2005 quickly spurred the
      development of the Janus kinase inhibitors. In one of the great victories of
      translational research in recent times, the first smallmolecule Janus kinase
      inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of
      ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk
      and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the
      management of a subset of myeloproliferative neoplasms (MPN): primary
      myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential
      thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only
      covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater
      potency are likely to offer better disease control and survival advantage in
      patients belonging to these categories, and possibly to the low-risk and
      intermediate-1 risk categories of MPN as well. But use of the Janus kinase
      inhibitors also probably has certain disadvantages, such as toxicity, resistance,
      withdrawal phenomenon, non-reversal of histology, and an implausible goal of
      disease clone eradication, some of which could offset the gains. In spite of
      this, Janus kinase inhibitors are here to stay, and for use in more than just
      myeloproliferative neoplasms. 

PMID- 25992204
TI  - Quality of life outcomes in patients with breast cancer.
AB  - Health-related quality of life is now considered an important endpoint in cancer
      clinical trials. It has been shown that assessing quality of life in cancer
      patients could contribute to improved treatment and could even serve as a
      prognostic factor along with medical parameters. This paper presents a review of
      quality of life outcomes in patients with breast cancer according to previous
      descriptive findings. This is a bibliographic review of the literature covering
      publications that appeared in English language biomedical journals between 1987
      and 2008. The search strategy included a combination of the key words quality of
      life and breast cancer in the titles of published articles. The major findings
      are summarized and presented under different headings: evaluation of health
      related quality of life i) at the time of diagnosis, ii) during treatment, and
      iii) after the completion of treatment. Breast cancer patients receiving
      chemotherapy might experience several side-effects and symptoms that have a
      negative effect on their quality of life. Also adjuvant hormonal therapies were
      found to have a similar negative impact on quality of life. Psychological
      distress-anxiety and depression were found to be common among breast cancer
      patients. Symptoms-pain, fatigue, and insomnia were among the most common
      symptoms reported. There was quite an extensive body of literature on quality of
      life in breast cancer patients. These papers have made a considerable
      contribution to improving breast cancer care. 

PMID- 25992205
TI  - Management of neuroblastoma: a study of first- and second-line chemotherapy
      responses, a single institution experience.
AB  - Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio
      sensitive but prone to relapse after initial remission. The aim of the current
      study was to study the results of the first- and second-line chemotherapy on the
      short-term response and long-term survival of children, and to further describe
      the side effects of treatment. Ninety-five children with advanced neuroblastoma
      were included in the study, divided into two groups according to the treatment
      strategy: 65 were treated by first-line chemotherapy alone, and 30 children who
      were not responding or relapsed after first-line chemotherapy were treated by
      second-line chemotherapy. External beam radiotherapy was given to bone and brain
      secondary cancers when detected. Staging workup was performed before, during and
      after management. Response was documented after surgery for the primary tumor.
      Median follow up was 32 months (range 24-60 months). Chemothe rapy was continued
      until toxicity or disease progression occurred, indicating interruption of
      chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo
      suppression, with grade II-III severity in 60% of the firstline and 70% of the
      second-line chemotherapy patients. Median total actuarial survival was nearly 51
      months for the first-line chemotherapy group and 30 months for the second-line
      line group, with a statistically significant difference between the two groups
      (P<0.01). 

PMID- 25992206
TI  - Chemotherapy for small cell lung cancer: a comprehensive review.
AB  - Combination chemotherapy is the current strategy of choice for treatment of small
      cell lung cancer (SCLC). Platinum containing combination regimens are superior to
      non-platinum regimens in limited stage-SCLC and possibly also in extensive stage
      SCLC as first and second-line treatments. The addition of ifosfamide to platinum
      containing regimens may improve the outcome but at the price of increased
      toxicity. Suboptimal doses of chemotherapy result in inferior survival. Early
      intensified, accelerated and high-dose chemotherapy gave conflicting results and
      is not considered a standard option outside of clinical trials. A number of newer
      agents have provided promising results when used in combination regimens, for
      example, gemcitabine, irinotecan and topotecan. However, more studies are
      required to appropriately evaluate them. There is a definitive role for
      radiotherapy in LD-SCLC. However, timing and schedule are subject to further
      research. Novel approaches are currently being investigated in the hope of
      improving outcome. 

PMID- 25992208
TI  - Chemotherapy and target therapy as neo-adjuvant approach for initially
      unresectable colorectal liver metastases.
AB  - Although surgery is the most effective treatment for liver metastases in
      colorectal cancer patients, only 15-20% of these patients are suitable for a
      radical surgical approach, and metastases recurrence may occur at follow up. In
      the last decade, the use of pre-operative chemotherapy in combination with new
      biological drugs has been introduced. We reviewed data of neo-adjuvant
      chemotherapy strategies aimed at increasing the resection rate of liver
      metastases in colorectal cancer patients who were initially considered
      unresectable. 

PMID- 25992207
TI  - A literature review to investigate the link between psychosocial characteristics
      and treatment adherence in cancer patients.
AB  - Adherence to medication has been recognized as a key issue in health outcomes and
      efforts to improve patients' adherence are being made by the pharmaceutical
      industry, experts, and government bodies alike. This paper presents a review of
      these issues according to previous descriptive findings. Relevant studies written
      in English, published in 1976 or later, were identified through Medline, Embase
      and PsycInfo databases and reviewed. Review articles and clinical trials were
      excluded; all observational studies and surveys were considered. Articles were
      reviewed for any discussion of patients' characteristics and psychosocial
      characteristics affecting adherence to cancer treatment. The search strategy
      included a combination of key words adherence and cancer in titles. The major
      findings are summarized and presented under two main headings: i) patients'
      characteristics; and ii) psychosocial characteristics. In general, factors
      associated with increased likelihood of adherence to cancer treatment included
      younger age, higher education, higher income and Caucasian ethnicity. With
      regards to the psychosocial factors, lower levels of depression and anxiety,
      optimism as well as social support seemed to have a positive effect on treatment
      adherence. Studies of patterns of care in cancer treatment can help identify
      challenges in health care provided to particular subgroups of cancer patients and
      can aid researchers in designing studies that account for such factors in
      clinical and outcomes' research. 

PMID- 25992209
TI  - Benefits of remote real-time side-effect monitoring systems for patients
      receiving cancer treatment.
AB  - In Australia, the incidence of cancer diagnoses is rising along with an aging
      population. Cancer treatments, such as chemotherapy, are increasingly being
      provided in the ambulatory care setting. Cancer treatments are commonly
      associated with distressing and serious side-effects and patients often struggle
      to manage these themselves without specialized real-time support. Unlike chronic
      disease populations, few systems for the remote real-time monitoring of cancer
      patients have been reported. However, several prototype systems have been
      developed and have received favorable reports. This review aimed to identify and
      detail systems that reported statistical analyses of changes in patient clinical
      outcomes, health care system usage or health economic analyses. Five papers were
      identified that met these criteria. There was wide variation in the design of the
      monitoring systems in terms of data input method, clinician alerting and
      response, groups of patients targeted and clinical outcomes measured. The
      majority of studies had significant methodological weaknesses. These included no
      control group comparisons, small sample sizes, poor documentation of clinical
      interventions or measures of adherence to the monitoring systems. In spite of the
      limitations, promising results emerged in terms of improved clinical outcomes
      (e.g. pain, depression, fatigue). Health care system usage was assessed in two
      papers with inconsistent results. No studies included health economic analyses.
      The diversity in systems described, outcomes measured and methodological issues
      all limited between-study comparisons. Given the acceptability of remote
      monitoring and the promising outcomes from the few studies analyzing patient or
      health care system outcomes, future research is needed to rigorously trial these
      systems to enable greater patient support and safety in the ambulatory setting. 

PMID- 25992210
TI  - An overview on the role of FLT3-tyrosine kinase receptor in acute myeloid
      leukemia: biology and treatment.
AB  - Hematopoiesis, the process by which the hematopoietic stem cells and progenitors
      differentiate into blood cells of various lineages, involves complex interactions
      of transcription factors that modulate the expression of downstream genes and
      mediate proliferation and differentiation signals. Despite the many controls that
      regulate hematopoiesis, mutations in the regulatory genes capable of promoting
      leukemogenesis may occur. The FLT3 gene encodes a tyrosine kinase receptor that
      plays a key role in controlling survival, proliferation and differentiation of
      hematopoietic cells. Mutations in this gene are critical in causing a
      deregulation of the delicate balance between cell proliferation and
      differentiation. In this review, we provide an update on the structure, synthesis
      and activation of the FLT3 receptor and the subsequent activation of multiple
      downstream signaling pathways. We also review activating FLT3 mutations that are
      frequently identified in acute myeloid leukemia, cause activation of more complex
      downstream signaling pathways and promote leukemogenesis. Finally, FLT3 has
      emerged as an important target for molecular therapy. We, therefore, report on
      some recent therapies directed against it. 

PMID- 25992211
TI  - Therapeutic strategies for synchronous and multiple liver metastases from
      colorectal cancer.
AB  - Metastasis in the liver is one of the most critical factors in the prognosis of
      patients with colorectal cancer. The incidence of synchronous liver metastasis
      has been found to be approximately 20-25%, but the optimal timing of surgical
      resection remains controversial. Neoadjuvant chemotherapy has also been found to
      be beneficial not only for initially unresectable but also resectable synchronous
      metastases and traditional surgical strategies of hepatic resection with past
      chemotherapeutic regimens have been used less and less over the past several
      years. This review will discuss treatments in association with the recently
      developed chemotherapeutic regimens. 

PMID- 25992212
TI  - Haematopoietic stem cell transplantation as first-line treatment in myeloma: a
      global perspective of current concepts and future possibilities.
AB  - Stem cell transplantation forms an integral part of the treatment for multiple
      myeloma. This paper reviews the current role of transplantation and the progress
      that has been made in order to optimize the success of this therapy. Effective
      induction chemotherapy is important and a combination regimen incorporating the
      novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct
      to stem cell transplantation and in some cases may potentially postpone the need
      for transplant. Different conditioning agents prior to transplantation have been
      explored: high-dose melphalan is most commonly used and bortezomib is a promising
      additional agent. There is no well-defined superior transplantation protocol but
      single or tandem autologous stem cell transplantations are those most commonly
      used, with allogeneic transplantation only used in clinical trials. The
      appropriate timing of transplantation in the treatment plan is a matter of
      debate. Consolidation and maintenance chemotherapies, particularly thalidomide
      and bortezomib, aim to improve and prolong disease response to transplantation
      and delay recurrence. Prognostic factors for the outcome of stem cell transplant
      in myeloma have been highlighted. Despite good responses to chemotherapy and
      transplantation, the problem of disease recurrence persists. Thus, there is still
      much room for improvement. Treatments which harness the graft-versus-myeloma
      effect may offer a potential cure for this disease. Trials of novel agents are
      underway, including targeted therapies for specific antigens such as vaccines and
      monoclonal antibodies. 

PMID- 25992213
TI  - Tamoxifen non-estrogen receptor mediated molecular targets.
AB  - Recent experimental studies revealing new biological effects of tamoxifen on
      tumor cells both expressing and not expressing different types of estrogen
      receptors (ERalpha and ERbeta) show new aspects of a seemingly well known agent.
      This review describes tamoxifen targets, the blocking of which leads to
      inhibition of tumor cell growth and angiogenesis, stimulation of programmed cell
      death (apoptosis, autophagia and necrosis), inhibition of multidrug resistance,
      invasion and metastasis. Since outcomes of tamoxifen action on cells are
      prognostically good from the point of view of both tumor growth/metastasis
      inhibition and tumor response to drug therapy, the authors believe this is an
      extremely important addition to tamoxifen antiestrogenic effect. Arguments are
      provided to consider the strategy of long-term tamoxifen treatment proposed by
      Professor Craig V. Jordan in the 1970s that is also applicable to the treatment
      of other tumors. This is, first of all, the fact that expression of estrogen
      receptor-beta that can also be targeted by tamoxifen therapy in solid tumors of
      practically all known sites and histologies. The authors believe that molecular
      biological screening of patients with respect to expression of tamoxifen cellular
      targets other than ERalpha and ERbeta is needed to use to the full all tamoxifen
      biological activities other than modulation of estrogen receptors during long
      term adjuvant therapy for cancers of various sites. 

PMID- 25992214
TI  - Radio-protective role of antioxidant agents.
AB  - Ionizing radiation interacts with biological systems to produce reactive oxygen
      species and reactive nitrogen species which attack various cellular components.
      Radio-protectors act as prophylactic agents to shield healthy cells and tissues
      from the harmful effects of radiation. Past research on synthetic radio
      protectors has brought little success, primarily due to the various toxicity
      related problems. Results of experimental research show that antioxidant
      nutrients, such as vitamin E and herbal products and melatonin, are protective
      against the damaging effects of radiation, with less toxicity and side effects.
      Therefore, we propose that in the future, antioxidant radio-protective agents may
      improve the therapeutic index in radiation oncology treatments. 

PMID- 25992216
TI  - Systemic adjuvant therapies in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors
      worldwide. Recent innovations in the treatment of metastatic disease have led to
      new therapeutic approaches being investigated in the adjuvant setting.
      Observation is the only current standard of care after radical nephrectomy,
      although there is evidence of efficacy of adjuvant use of vaccine among all the
      strategies used. This article aims to collect published experiences with systemic
      adjuvant approaches in RCC and to describe the results of past and ongoing phase
      III clinical trials in this field. We explored all the systemic treatments,
      including chemotherapy, immunotherapy and targeted drugs while alternative
      approaches have also been described. Appropriate selection of patients who would
      benefit from adjuvant therapies remains a crucial dilemma. Although the
      international guidelines do not actually recommend any adjuvant treatment after
      radical surgery for RCC, no conclusions have yet been drawn pending the results
      of the promising ongoing clinical trials with the target therapies. The
      significant changes that these new drugs have made on advanced disease outcome
      could represent the key to innovation in terms of preventing recurrence, delaying
      relapse and prolonging survival after radical surgery for RCC. 

PMID- 25992215
TI  - Mechanisms of virus immune evasion lead to development from chronic inflammation
      to cancer formation associated with human papillomavirus infection.
AB  - Human papillomavirus (HPV) has developed strategies to escape eradication by
      innate and adaptive immunity. Immune response evasion has been considered an
      important aspect of HPV persistence, which is the main contributing factor
      leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6
      and E7 are potentially recognized by the immune system. The major
      histocompatibility complex (MHC) class I molecules are patrolled by natural
      killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of
      recognition is a main target for the strategies of immune evasion deployed by
      viruses. The viral immune evasion proteins constitute useful tools to block
      defined stages of the MHC class I presentation pathway, and in this way HPV
      avoids the host immune response. The long latency period from initial infection
      to persistence signifies that HPV evolves mechanisms to escape the immune
      response. It has now been established that there are oncogenic mechanisms by
      which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and
      inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins
      can give rise to an increased immortalization and genomic instability.
      Overexpression of NF-kappaB in cervical and penile cancers suggests that NF
      kappaB activation is a key modulator in driving chronic inflammation to cancer.
      HPV oncogene-mediated suppression of NF-kappaB activity contributes to HPV escape
      from the immune system. This review focuses on the diverse mechanisms of the
      virus immune evasion with HPV that leads to chronic inflammation and cancer. 

PMID- 25992217
TI  - The management of low-stage non-seminomatous germ cell tumors.
AB  - The prognosis of patients with stage I non-seminomatous germ cell tumors is in
      general very good. However, a large number of patients relapse with metastatic
      disease after orchidectomy Therefore, adjuvant treatment, in the form of either
      chemotherapy or retroperitoneal dissection is recommended, although active
      surveillance has been found to be as good a way of treating these patients with
      overall excellent results. 

PMID- 25992218
TI  - Axillary dissection compared to sentinel node biopsy for the treatment of
      pathologically node-negative breast cancer: a meta-analysis of four randomized
      trials with long-term follow up.
AB  - Sentinel lymph node biopsy is now accepted as the initial approach for women with
      early stage breast cancer with clinically node-negative disease. We performed a
      pooled analysis of trials comparing axillary lymph node dissection to sentinel
      lymph node biopsy in patients with early stage breast cancer and pathologically
      negative sentinel lymph node analysis. A systematic MEDLINE review identified
      four randomized trials of axillary dissection versus sentinel lymph node biopsy
      in lymph node-negative early stage breast cancer patients. A meta-analysis was
      performed for survival and relapse. The combined analyses of these four trials
      found no significant difference in overall survival (relative risk [RR] 1.15;
      P=0.16; 95% CI: 0.95-1.39), breast cancer-specific (RR 1.03; P=0.85; 95% CI:
      0.751.43) and disease-free survival (RR 1.07; P=0.3; 95% CI: 0.94-1.21), distant
      metastases (RR 1; P=0.98; 95% CI: 0.76-1.32), and ipsilateral breast recurrence
      (RR 1.64; P=0.34; 95% CI: 0.60-4.47) associated with sentinel lymph node biopsy.
      In particular, a similar rate of nodal recurrences was seen after sentinel lymph
      node biopsy (RR 1.74; P=0.13; 95% CI: 0.86-3.53). Axillary dissection does not
      confer a survival benefit nor prevent further nodal relapses in the setting of
      early stage, pathologically lymph node-negative breast cancer. 

PMID- 25992220
TI  - Spontaneous regression of breast carcinoma: review of English publications from
      1753 to 1897.
AB  - Regression is an important phenomenon in oncology. Two reviews in 2011 dealt at
      length with what in modern parlance may be called its permutations and
      combinations. Specifically, in both 1982 and 1987, when its occurrence in breast
      cancer was presented from two centers, the oldest accounts of it were dated back
      to 1900. Therefore, a search for much older English literature was undertaken in
      order to widen current knowledge of this important problem. Consequently, a
      published long case dating back to 1897 is abridged and a short 1846 case is also
      noted. Furthermore, general etiological concepts are exemplified as far back as
      1753. It is concluded that the history of cancer regression is like fishing in an
      ocean of this illness. However, the findings are deemed to complement what modern
      historical accounts lack. 

PMID- 25992219
TI  - Role of viruses in oral squamous cell carcinoma.
AB  - The etiology of oral squamous cell carcinoma (OSCC) is complex and involves many
      factors. The most clearly defined risk factors are smoking and alcohol, which
      substantially increase the risk of oral SCC. However, despite this clear
      association, a substantial proportion of patients develop OSCC without exposure
      to them, emphasizing the role of other risk factors such as genetic
      susceptibility and oncogenic viruses. Some viruses are strongly associated with
      OSCC while the association of others is less frequent and may depend on co
      factors for their carcinogenic effects. Therefore, the exact role of viruses must
      be evaluated with care in order to improve the diagnosis and treatment of OSCC. 

PMID- 25992221
TI  - The role of perioperative radiotherapy in gastric cancer.
AB  - Gastric cancer is one of the most common neoplasms and a main cause of cancer
      related mortality worldwide. Surgery remains the mainstay for cure and is
      considered for all patients with potentially curable disease. However, despite
      the fact that surgery alone usually leads to favorable outcomes in early stage
      disease, late diagnosis usually means a poor prognosis. In these settings,
      multimodal therapy has become the established treatment for locally advanced
      tumors, while the high risk of locoregional relapse has favored the inclusion of
      radiotherapy in the comprehensive therapeutic strategy. We provide a critical,
      non-systematic review of gastric cancer and discuss the role of perioperative
      radiation therapy in its treatment. 

PMID- 25992222
TI  - Tumorigenesis: cell defense against hypoxia?
AB  - Microenvironmental elements can directly contribute to the induction and the
      maintenance of tumor. Oxygen is the main element in the cell microenvironment and
      hypoxia can affect the process of tumorigenesis. In response to hypoxia, cells
      change their pattern and characteristics. These changes suggest that it is not
      just adaptation, but some sort of cell defense against hypoxia. If hypoxia is
      corrected, then cell defense mechanisms are interrupted. An examination of the
      process of tumorigenesis helps to design better therapeutic strategies. A
      systematic review of the English literature was conducted by searching PubMed,
      Google Scholar, and ISI Web databases for studies on changes that defend and help
      cells to live in a hypoxic microenvironment. Cells respond to hypoxia by de
      differentiation and an increase in heat shock proteins. Angiogenesis and
      deviation of inflammatory response in favor of hypoxic cell survival also defend
      and save the oxygen-starved cells from death. Finally, anti-angiogenic therapies
      and more hypoxia enhance metastasis, as tumors with low oxygen concentration are
      more malignant than tumors with high oxygen concentration. All these enable cells
      to migrate away from low oxygen areas and seek a more conducive microenvironment.
      Therapies that make the microenvironment more hypoxic need to be revised. This
      has been done for anti-angiogenic therapies, previously considered to be anti
      tumor approaches. Effective therapies may be correcting therapies which direct
      the tumor microenvironment towards natural physical/chemical condition.
      Correcting therapies either bring back tumor cells to a normal form (correct
      tumor cells) or help the immune system to eradicate tumor cells which can not be
      corrected. 

PMID- 25992223
TI  - Sampling versus systematic full lymphatic dissection in surgical treatment of non
      small cell lung cancer.
AB  - The extent of mediastinal lymph node assessment during surgery for non-small cell
      cancer remains controversial. Different techniques are used, ranging from simple
      visual inspection of the unopened mediastinum to an extended bilateral lymph node
      dissection. Furthermore, different terms are used to define these techniques.
      Sampling is the removal of one or more lymph nodes under the guidance of pre
      operative findings. Systematic (full) nodal dissection is the removal of all
      mediastinal tissue containing the lymph nodes systematically within anatomical
      landmarks. A Medline search was conducted to identify articles in the English
      language that addressed the role of mediastinal lymph node resection in the
      treatment of non-small cell lung cancer. Opinions as to the reasons for favoring
      full lymphatic dissection include complete resection, improved nodal staging and
      better local control due to resection of undetected micrometastasis. Arguments
      against routine full lymphatic dissection are increased morbidity, increase in
      operative time, and lack of evidence of improved survival. For complete resection
      of non-small cell lung cancer, many authors recommend a systematic nodal
      dissection as the standard approach during surgery, and suggest that this
      provides both adequate nodal staging and guarantees complete resection. Whether
      extending the lymph node dissection influences survival or recurrence rate is
      still not known. There are valid arguments in favor in terms not only of an
      improved local control but also of an improved long-term survival. However, the
      impact of lymph node dissection on long-term survival should be further assessed
      by large-scale multicenter randomized trials. 

PMID- 25992224
TI  - Modulation of insulin-like growth factor-1 receptor and its signaling network for
      the treatment of cancer: current status and future perspectives.
AB  - Based on over three decades of pre-clinical data, insulin-like growth factor-1
      receptor (IGF-1R) signaling has gained recognition as a promoter of
      tumorogenesis, driving cell survival and proliferation in multiple human cancers.
      As a result, IGF-1R has been pursued as a target for cancer treatment. Early
      pioneering efforts targeting IGF-1R focused on highly selective monoclonal
      antibodies, with multiple agents advancing to clinical trials. However, despite
      some initial promising results, recent clinical disclosures have been less
      encouraging. Moreover, recent studies have revealed that IGF-1R participates in a
      dynamic and complex signaling network, interacting with additional targets and
      pathways thereof through various crosstalk and compensatory signaling mechanisms.
      Such mechanisms of bypass signaling help to shed some light on the decreased
      effectiveness of selective IGF-1R targeted therapies (e.g. monoclonal antibodies)
      and suggest that targeting multiple nodes within this signaling network might be
      necessary to produce a more effective therapeutic response. Additionally, such
      findings have led to the development of small molecule IGF-1R inhibitors which
      also co-inhibit additional targets such as insulin receptor and epidermal growth
      factor receptor. Such findings have helped to guide the design rationale of
      numerous drug combinations that are currently being evaluated in clinical trials.

PMID- 25992225
TI  - Radiation therapy for primary central nervous system lymphoma.
AB  - Up until the late 1970s, radiation therapy played an important role in the
      treatment of primary central nervous system lymphoma (PCNSL) but more recently
      its role has changed due to the increased use of systemic chemotherapy. In this
      article, the current status of radiotherapy for PCNSL and optimal forms of
      radiotherapy, including the treatment volume and radiation dose, are discussed.
      Data from nationwide Japanese surveys of PCNSL patients treated with radiation
      therapy suggest that the prognosis of PCNSL patients improved during the 1990s,
      in part due to the use of high-dose methotrexate-containing chemotherapy. The
      prognosis of patients treated with radiation alone also improved. Radiotherapy
      still seems to play an important role in the attempt to cure this disease. 

PMID- 25992226
TI  - Research biopsies in the context of early phase oncology studies: clinical and
      ethical considerations.
AB  - The Personalized Medicine approach in oncology is a direct result of an improved
      understanding of complex tumor biology and advances in diagnostic technologies.
      In recent years, there has been an increased demand for archival and fresh tumor
      analysis in early clinical trials to foster proof-of-concept biomarker
      development, to understand resistance mechanisms, and ultimately to assess
      biological response. Although phase I studies are aimed at defining drug safety,
      pharmacokinetics, and to recommend a phase II dose for further testing, there is
      now increasing evidence of mandatory tumor biopsies even at the earliest dose
      finding stages of drug development. The increasing demand for fresh tumor
      biopsies adds to the complexity of novel phase I studies and results in different
      challenges, ranging from logistical support to ethical concerns. This paper
      investigates key issues, including patients' perceptions of research biopsies,
      the need for accurate informed consent, and alternative strategies that may guide
      the drug development process. 

PMID- 25992227
TI  - Hormonal therapy in metastatic prostate cancer: current perspectives and
      controversies.
AB  - Ever since the introduction of androgen deprivation therapy (ADT) in prostate
      cancer, various controversial aspects of hormonal therapy have come to light.
      There has been tremendous progress in this area, marked by several important
      developments in the availability of various new androgen-suppressing agents and
      refinements to the existing therapies. Parallel to these developments, various
      more debatable aspects have arisen in the use of these therapies with regards to
      their negative impact on quality of life parameters. Various modifications in
      these hormonal agents, their doses, and protocols have been tried in different
      scenarios in order to improve ADT tolerability. As a result, these controversies
      continue to evolve even with optimal use of the androgen ablation therapy. This
      review assesses the present status of hormonal therapy in metastatic prostate
      cancer and specifically deals with those aspects of androgen ablation therapy
      that are still a subject of debate. In spite of the fact that various trials have
      been conducted, some of which are still ongoing, the multitude of questions
      related to the best possible use of these hormonal agents have still not been
      answered. Treatment guidelines concerning these issues are continuing to evolve
      as progress continues to be made in this field. 

PMID- 25992228
TI  - Clinical and surgical-pathological staging in early non-small cell lung cancer.
AB  - Staging is of the utmost importance in the evaluation of a patient with non-small
      cell lung cancer (NSCLC) because it defines the actual extent of the disease.
      Accurate staging allows multidisciplinary oncology teams to plan the best
      surgical or medical treatment and to predict patient prognosis. Based on the
      recommendation of the International Association for the Study of Lung Cancer
      (IASLC), a tumor, node, and metastases (TNM) staging system is currently used for
      NSCLC. Clinical staging (c-TNM) is achieved via non-invasive modalities such as
      examination of case history, clinical assessment and radiological tests.
      Pathological staging (p-TNM) is based on histological examination of tissue
      specimens obtained with the aid of invasive techniques, either non-surgical or
      during the intervention. This review is a critical evaluation of the roles of
      current pre-operative staging modalities, both invasive and non-invasive. In
      particular, it focuses on new techniques and their role in providing accurate
      confirmation of patient TNM status. It also evaluates the surgical-pathological
      staging modalities used to obtain the true-pathological staging for NSCLC. 

PMID- 25992230
TI  - The epithelial-mesenchymal interactions: insights into physiological and
      pathological aspects of oral tissues.
AB  - In the human biological system, the individual cells divide and form tissues and
      organs. These tissues are hetero-cellular. Basically any tissue consists of an
      epithelium and the connective tissue. The latter contains mainly mesenchymally
      derived tissues with a diversified cell population. The cell continues to grow
      and differentiate in a pre-programmed manner using a messenger system. The
      epithelium and the mesenchymal portion of each tissue have two different origins
      and perform specific functions, but there is a well-defined interaction
      mechanism, which mediates between them. Epithelial mesenchymal interactions
      (EMIs) are part of this mechanism, which can be regarded as a biological
      conversation between epithelial and mesenchymal cell populations involved in the
      cellular differentiation of one or both cell populations. EMIs represent a
      process that is essential for cell growth, cell differentiation and cell
      multiplication. EMIs are associated with normal physiological processes in the
      oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary
      gland development, palatogenesis, and also pathological processes, such as oral
      cancer. This paper focuses the role EMIs in odontogenesis, salivary gland
      development, palatogenesis and oral cancer. 

PMID- 25992229
TI  - The Role of microRNAs in Stemness of Cancer Stem Cells.
AB  - Cancer is one of the most important diseases of humans, for which no cure has
      been found so far. Understanding the causes of cancer can pave the way for its
      treatment. Alteration in genetic elements such as oncogenes and tumor suppressor
      genes results in cancer. The most recent theory for the origin of cancer has been
      provided by cancer stem cells (CSCs). Tumor-initiating cells (T-ICs) or CSCs are
      a small population isolated from tumors and hematologic malignancies. Since CSCs
      are similar to embryonic stem cells (ESCs) in many aspects (such as pluripotency
      and self-renewal), recognizing the signaling pathways through which ESCs maintain
      their stemness can also help identify CSC signaling. One component of these
      signaling pathways is non-coding RNAs (ncRNAs). ncRNAs are classified in two
      groups: microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs undergo
      altered expression in cancer. In this regard, they are classified as Onco-miRNAs
      or tumor suppressor miRNAs. Some miRNAs play similar roles in ESCs and CSCs, such
      as let-7 and miR-302. This review focuses on the miRNAs involved in stemness of
      ESCs and CSCs by presenting a summary of the role of miRNAs in other tumor cells.

PMID- 25992231
TI  - The role of epidermal growth factor-like module containing mucin-like hormone
      receptor 2 in human cancers.
AB  - G-protein coupled receptors (GPCRs) are among the most diverse and ubiquitous
      proteins in all of biology. The epidermal growth factor-seven span transmembrane
      (EGF-TM7) subfamily of adhesion GPCRs is a small subset whose members are mainly
      expressed on the surface of leukocytes. The EGF domains on the N-terminus add
      significant size to these receptors and they are considered to be among the
      largest members of the TM7 family. Although not all of their ligands or
      downstream targets have been identified, there is evidence implicating the EGF
      TM7 family diverse processes such as cell adhesion, migration, inflammation, and
      autoimmune disease. Recent studies have identified expression of EGF-TM7 family
      members on human neoplasms including those of the thyroid, stomach, colon, and
      brain. Their presence on these tissues is not surprising given the ubiquity of
      GPCRs, but because their functional significance and pathways are not completely
      understood, they are of tremendous clinical and scientific interest. Current
      evidence suggests that expression of certain EGF-TM7 receptors is correlated with
      tumor grade, confers a more invasive phenotype, and increases the likelihood of
      metastatic disease. In this review, we will discuss the structure, function, and
      regulation of these receptors. We also describe the expression of these receptors
      in human cancers and explore their potential mechanistic significance. 

PMID- 25992232
TI  - Oral field cancerization: an update on current concepts.
AB  - There always exists a field with genetically altered cells with a high risk of
      developing premalignant and malignant lesions. It may often happen that an
      individual stem cell is genetically altered and can cause the formation of a
      clone or a patch which is likely to turn into a tumor. This explains the higher
      recurrence rates following tumor resections. It is essential to identify and to
      treat this field in order to have greater chances to prevent cancer and achieve a
      better outcome. This article reports concepts, theories and markers for the
      assessment of field cancerization. 

PMID- 25992233
TI  - The current trend of administering a patient-generated index in the oncological
      setting: a systematic review.
AB  - The patient-generated index (PGI) is a more novel approach to evaluating health
      related quality of life (HRQOL) that allows patients to formulate their own
      responses in an open-ended format in order to measure HRQOL based on each
      patient's own stated goals and expectations. To date the use of PGI in the
      setting of patients diagnosed with cancer remains relatively less common compared
      to other health conditions. This systematic review primarily aims to identify
      current literature in which PGI has been used as a tool to assess quality of life
      in cancer patients. A systematic review using the MEDLINE database from January
      1990 to July 2013 was performed with the following search terms to identify the
      implementation of PGI in oncology settings: (PGI OR patient generated index OR
      patient-generated OR patient-reported OR patient generated OR patient reported)
      AND (cancer OR oncology OR tumor OR neoplasm OR malignancy). Of the 2167 papers
      initially identified, 10 papers evaluated quality of life in oncology patients by
      collecting free-form responses from the patient, 4 of which actually used PGI. An
      overarching theme observed in these studies highlighted the concerns mentioned by
      patients that were not targeted or detected by standardized quality of life
      measures. While implementing the PGI may require slightly more investment of
      resources in the beginning, the potential implications of allowing patients to
      characterize their quality of life on their own terms are tremendous. 

PMID- 25992236
TI  - Wedge resection and segmentectomy in patients with stage I non-small cell lung
      carcinoma.
AB  - The use of sublobar resections as definitive management in stage I non-small cell
      lung carcinoma is a controversial topic in the medical community. We intend to
      report the latest developments and trends in relative indications for each of the
      above-mentioned surgical approaches for the treatment of stage I non-small cell
      lung carcinoma as well as the results of studies regarding local recurrence,
      disease-free survival and five-year survival rates. We reviewed 45 prospective
      and retrospective studies conducted over the last 25 years listed in the Pubmed
      and Scopus electronic databases. Trials were identified through bibliographies
      and a manual search in journals. Authors, citations, objectives and results were
      extracted. No meta-analysis was performed. Validation of results was discussed.
      Segmentectomies are superior to wedge resections in terms of local recurrences
      and cancer-related mortality rates. Sublobar resections are superior to lobectomy
      in preserving the pulmonary parenchyma. High-risk patients should undergo
      segmentectomy, whereas lobectomies are superior to segmentectomies only for
      tumors >2 cm (T2bN0M0) in terms of disease-free and overall 5-year survival. In
      most studies no significant differences were found in tumors <2 cm. Disease-free
      surgical margins are crucial to prevent local recurrences. Systematic
      lymphadenectomy is mandatory regardless of the type of resection used. In
      sublobar resections with less thorough nodal dissections, adjuvant radiotherapy
      can be used. This approach is preferable in case of prior resection. In pure
      bronchoalveolar carcinoma, segmentectomy is recommended. Sublobar resections are
      associated with a shorter hospital stay. The selection of the type of resection
      in T1aN0M0 tumors should depend on characteristic of the patient and the tumor.
      Patient age, cardiopulmonary reserve and tumor size are the most important
      factors to be considered. However further prospective randomized trials are
      needed to investigate the efficacy of minimal resections in early lung cancer
      patients. 

PMID- 25992234
TI  - Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy
      and mode of action.
AB  - Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes
      half a million deaths worldwide. Being an aggressive cancer, its incidence
      exceeds 700,000 new cases per year worldwide with a median survival of 6-8
      months. Despite advances in prognosis and early detection, effective HCC
      chemoprevention or treatment strategies are still lacking, therefore its dismal
      survival rate remains largely unchanged. This review will characterize currently
      available chemotherapeutic drugs used in the treatment of HCC. The respective
      mode(s) of action, side effects and recommendations will be also described for
      each drug. 

PMID- 25992237
TI  - Target therapy in metastatic pheochromocytoma: current perspectives and
      controversies.
AB  - Most of the pheochromocytomas (PCCs) are benign neoplasms, but when they are
      malignant, they can be difficult to treat. Despite advances in diagnosis and
      imaging, it remains an untreatable tumor, when metastases develop. A deeper
      understanding of the alteration of the specific molecular pathways causing
      malignant PCCs might hopefully lead in the future to the development of multiple
      molecular-targeted therapies to treat it successfully. Clinical experience and
      the use of murine models of metastatic PCCs have helped introduce new
      experimental treatment options which will significantly help the PCCs community
      explore novel targeted therapies that have already shown promising results in
      many other types of tumors. 

PMID- 25992238
TI  - The role of neoadjuvant chemotherapy in the management of locally advanced cervix
      cancer: a systematic review.
AB  - Cervical cancer is the second most common cancer in women. Neoadjuvant
      chemotherapy for patients with locally advanced cervix cancer has comparable
      benefits to concurrent chemoradiotherapy (CCRT), but with fewer side effects.
      This systematic review aims to provide a comprehensive summary of the benefits of
      neoadjuvant chemotherapy for the management of locally advanced cervix cancer
      from stage IB2 (tumor >4.0 cm) to IIIB (tumor extending to the pelvic wall and/or
      hydronephrosis). Our primary objective was to assess benefits in terms of
      survival. The data source included the USA national library of medicine, Medline
      search, and the National Cancer Institute PDQ Clinical Protocols. Inclusion
      criteria for consideration in the current systematic review included studies
      published between January 1997 and December 2012. In terms of histology, they had
      to be focused on squamous cell carcinoma, adenosquamous carcinoma, and/or
      adenocarcinoma. Patients should be either chemotherapy naive or cervix cancer
      chemotherapy naive, and have a performance status <=2. The search in the above
      mentioned scientific websites led to identify 49 publications, 19 of which were
      excluded, as they did not meet the inclusion criteria of this systematic review.
      Therefore only 30 studies were deemed eligible. Data was collected from 1760
      patients enrolled in the current systematic review study. The mean age was 45.2
      years. The mean tumor size was 4.7 cm. The most commonly used chemotherapies were
      cisplatin doublets. Paclitaxel was the most commonly used chemotherapeutic agent
      in the doublets. The mean chemotherapy cycles were 2.7. After chemotherapy,
      patients underwent surgery after a mean time of 2.5 weeks. The standard operation
      was radical hysterectomy with pelvic lymphadenectomy. Chemotherapy achieved an
      objective response rate of 84%. The 5-year progression-free survival and overall
      survival were 61.9% and 72.8% respectively. The treatment protocol was associated
      with a mild early toxicity profile. Leucopenia and neutropenia were the most
      common side effects. Late toxicity was also generally mild and mainly associated
      with bladder dysfunction and vaginal dehiscence. The quality of the studies was
      assessed using the Newcastle-Ottawa quality assessment scale. Neoadjuvant
      chemotherapy achieved comparable survival results to CCRT, and was associated
      with less toxicity. 

PMID- 25992239
TI  - Dormancy of growth-stunted malignant melanoma: sustainable and smoldering
      patterns.
AB  - The presentations of primary and metastatic cutaneous malignant melanoma (CMM)
      are very diverse. Evidence increasingly indicates that single CMM cells spread to
      distant sites quite early during cancer progression and are soon eliminated
      before they become clinically detectable. However bulky metastases which appear
      at a later stage might derive from some of these early neoplastic cells. It seems
      that local CMM single cell micro-metastases commonly predict sentinel lymph node
      involvement without overtly reflecting CMM progression to bulky visceral
      metastases. This study is intended to review the current understanding of the
      mechanisms underlying two CMM presentations. The first is the long interval,
      apparently disease-free, with persistent CMM dormancy, which may precede overt
      metastatic growth. Immunosurveillance may induce dormancy in single CMM cells
      disseminated in the body by blocking their proliferation cycle. The second is the
      so-called CMM smoldering phenomenon, which is marked by an alternate progression
      and regression of CMM locally with metastases that wax and wane for long periods
      of time over restricted skin areas. These very diverse patterns of CMM
      progression are likely to be ascribable to a number of biological factors,
      including the activation of CMM stem cells, and the combined phenotypic
      heterogeneity and variability in proliferative amplification in CMM cell
      clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the
      induction of a specific stromal structure and vascular response are required. In
      this context, most early CMM tumors are in part controlled by lymphocyte-mediated
      responses before they become clinically detectable. However both the role of
      immune-surveillance and the mechanisms underlying both persistent and smoldering
      CMM dormancy remain unclear. 

PMID- 25992240
TI  - BRAF Mutation in Hairy Cell Leukemia.
AB  - BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated
      protein kinase (MAPK) signaling pathway. A mutation in the RAF gene, especially
      in BRAF protein, leads to an increased stimulation of this cascade, causing
      uncontrolled cell division and development of malignancy. Several mutations have
      been observed in the gene coding for this protein in a variety of human
      malignancies, including hairy cell leukemia (HCL). BRAF V600E is the most common
      mutation reported in exon15 of BRAF, which is observed in almost all cases of
      classic HCL, but it is negative in other B-cell malignancies, including the HCL
      variant. Therefore it can be used as a marker to differentiate between these B
      cell disorders. We also discuss the interaction between miRNAs and signaling
      pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF
      protein inhibitors may represent an effective treatment. In this review we have
      evaluated the role of the mutation of the BRAF gene in the pathogenesis and
      progression of HCL. 

PMID- 25992241
TI  - Bisphosphonate-related osteonecrosis of the jaw: specificities.
AB  - Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe complication
      that has recently emerged in patients treated with intravenous bisphosphonates
      for malignant diseases. This complication usually presents after a minor local
      trauma during a dental treatment. Several etiopathogenic mechanisms of this
      pathological condition have been proposed, but no model can explain all
      morphological changes observed at the macroscopic and microscopic level. BRONJ is
      likely to be related to direct toxicity in the bone and soft tissue cells, due to
      nitrogen-containing bisphosphonates. This review elucidates the clinical
      indications and mechanism of action of bisphosphonates, reports some clinical
      diagnostic criteria for BRONJ, describe the histopathological criteria for BRONJ
      diagnosis, the potential triggering pathways and the available treatment
      strategies. 

PMID- 25992242
TI  - Review of Cisplatin and oxaliplatin in current immunogenic and monoclonal
      antibody treatments.
AB  - Platinum-based chemotherapy agents initially transformed cancer treatment.
      However their effectiveness peaked as combined regimes showed little additional
      benefit in trials. New research frontiers developed with the discovery that
      conventional chemotherapy can induce immunological cell death by recruiting high
      mobility group box 1 protein through T-cell immunity. Simultaneously monoclonal
      antibody agents (not effective as monotherapies) showed good results in
      combination with conventional chemotherapy. Some of these combinations are
      currently in use and researchers hope to develop regimes which can offer
      substantial benefits. Several resistance mechanisms against platinum compounds
      are known, but more knowledge is still needed to gain a full understanding. It
      seems reasonable therefore to revisit the pharmacology of these agents, which may
      also lead to identify rational combinations with monoclonal agents providing
      regimes with less toxicity and better efficacy. This article reviews the
      pharmacology of cisplatin and oxaliplatin and explores their possible association
      with monoclonal antibody treatments. 

PMID- 25992243
TI  - Epithelioid hemangioendothelioma: an overview and update on a rare vascular
      tumor.
AB  - Epithelioid hemangioendothelioma is a rare vascular tumor, described for the
      first time in 1975 by Dail and Liebow as an aggressive bronchoalveolar cell
      carcinoma. The etiology is still a dilemma. Studies about suggestive hypothesis
      are ongoing. Most of the times it affects lung, liver and bones, although this
      kind of tumor may involve the head and neck area, breast, lymph nodes,
      mediastinum, brain and meninges, the spine, skin, abdomen and many other sites.
      Because of its heterogeneous presentation, as it represents less than 1% of all
      the vascular tumors, it is often misdiagnosed and not suitably treated, leading
      to a poor prognosis in some cases. Over 50-76% of the patients are asymptomatic.
      A small number of them complains respiratory symptoms. Bone metastases might
      cause pathological fractures or spine compression, if they arise in vertebrae.
      Imaging is necessary to determine morphological data, the involvement of
      surrounding tissues, and potentially the cleavage plan. It is important to
      recognize the expression of vascular markers (Fli-1 and CD31 are endothelial
      specific markers), and the microscopic evidence of vascular differentiation to
      make a correct diagnosis, as many pulmonary diseases show multiple nodular
      lesions. Because of its rarity, there is no standard for treatment. We focused on
      radiotherapy as a good therapeutic option: despite the poor prognosis, evidence
      is in favor of radiotherapy which offers local pain control with good tolerance
      and better quality of life at least at a one-year follow-up in most of cases.
      Further studies are needed to establish the standard radiation dose to be used
      for locoregional control of such a complex and extremely rare disease. 

PMID- 25992244
TI  - Why they don't understand?

PMID- 25992245
TI  - An overview on Leishmania vaccines: A narrative review article.
AB  - Leishmaniasis is one of the major health problems and categorized as a class I
      disease (emerging and uncontrolled) by World Health Organization (WHO), causing
      highly significant morbidity and mortality. Indeed, more than 350 million
      individuals are at risk of Leishmania infection, and about 1.6 million new cases
      occur causing more than 50 thousands death annually. Because of the severe
      toxicity and drug resistance, present chemotherapy regimen against diverse forms
      of Leishmania infections is not totally worthwhile. However, sound immunity due
      to natural infection, implies that vigor cellular immunity against Leishmania
      parasites, via their live, attenuated or killed forms, can be developed in dogs
      and humans. Moreover, genetically conserved antigens (in most of Leishmania
      species), and components of sand fly saliva confer potential immunogenic
      molecules for Leishmania vaccination. Vaccines successes in animal studies and
      some clinical trials clearly justify more researches and investments illuminating
      opportunities in suitable vaccine designation. 

PMID- 25992246
TI  - The role of sera from equine grass sickness on apoptosis induction in PC12 Tet
      off p53 cell line.
AB  - The pathogenesis of equine grass sickness (EGS) has not fully understood. A
      better understanding of the exact pathogenesis of diseases can help to make an
      accurate diagnosis. Previous studies reported some pathological damage of
      neuronal cells in EGS patients. In this study, primarily cytotoxicity of serum
      from three clinically EGS-diagnosed horses on PC12 Tet-off (PTO) cells was
      assessed. Subsequently, the apoptotic tests including cytochrome C release,
      caspase-3/7 activity measurement and DNA fragmentation assay were conducted to
      clarify the apoptotic effect of serum from EGS patients. Addition of serum from
      EGS patients at concentrations higher than 25% on PTO cells resulted in a
      significant cytotoxicity in Alamar blue reduction assay compared with serum from
      healthy horses. All three apoptotic endpoints showed that the serum from EGS
      patients does have capability to induce apoptosis. A remarkable up regulation of
      cytochrome C release accompanied with concentration- and time-dependent
      augmentation in caspase-3/7 activity and ultimately DNA fragmentation were
      observed. Our data suggest that serum from EGS patients might have potentially
      neurotoxic compounds, which exerts cytotoxic and apoptotic effects on neuronal
      cells. Moreover, the EGS serum-induced apoptosis attributes to augmentation of
      cytochrome C release and caspase-3/7 activity. 

PMID- 25992247
TI  - Study of disbudding goat kids following injection of clove oil essence in horn
      bud region.
AB  - This study was performed to evaluate the efficacy of injection of essential oil
      of Eugenia caryophyllata in the kid horn buds, as a new chemical technique for
      disbudding. Five-day-old healthy goat kids from both sexes (n = 16) were divided
      randomly into 4 equal groups. In groups 1, 2 and 3, 0.2 mL of clove essence and
      in group 4 (control) 0.2 mL of normal saline was injected into the left horn bud
      of goat kids. Right horn bud in all kids was considered to ensure that they are
      horned. During the study, the rate of horn growth were evaluated in determined
      time intervals between groups 1 and 4. Tissue samples were taken from right and
      left horn bud in groups 2 and 3, at five and ten days after clove essence
      injection, for microscopic study. The results of the study showed that the clove
      essence stopped horn growth, whereas there was no significant difference in horn
      growth rate between left and right horns after injection of normal saline, in
      group 4. Histopathological study showed that injection of clove essence caused
      complete necrosis of epidermis and underlying dermis with collagenolysis in horn
      bud tissues, 5 days after injection and then progress in healing process was
      observed after 10 days. According to the results of this study, it can be
      concluded that the injection of clove essence is an effective method to stop horn
      growth without any undesirable effects on clinical parameters in goat kids. 

PMID- 25992248
TI  - The histological and histometrical effects of Urtica dioica extract on rat's
      prostate hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common disease in human that gradual
      overgrowth of the prostate gland leads to impinge on the urethra with impairment
      in urinary function. Numerous plants improve uncontrolled growth of the prostate
      gland and improve urinary tract symptoms associated with BPH. In this study, 25
      healthy adult male Wistar rats were divided randomly in five groups: G1 (Control
      group) received ordinary feed without any treatment, G2 received 10 mg kg(-1)
      testosterone subcutaneously, G3 received 50 mg kg(-1) nettle root extract orally,
      G4 received 50 mg kg(-1) nettle root extract orally and 10 mg kg(-1)
      testosterone, G5 received 10 mg kg(-1) almond oil (Almond oil was used as
      testosterone solvent) subcutaneously. After six weeks, volume and weight of each
      lobe were measured and samples were taken. The 5 to 6 um thickness sections were
      made using paraffin embedding method and stained by hematoxylin and eosin and
      periodic acid-Schiff. The results showed that prostate volume and ratio of
      prostate to body weight were increased significantly in the testosterone.
      Histological and histometrical results showed that dorsal and lateral type 1 and
      2 lobes were not changed significantly but the ventral and anterior lobes have
      changed significantly. Over all, the nettle root could prevent from some of
      prostatic hyperplasia effects, so that percentage of folded alveoli in ventral
      lobe reduced insignificantly. 

PMID- 25992249
TI  - The effect of Cinnamomum zeylanicum essential oil on chemical characteristics of
      Lyoner- type sausage during refrigerated storage.
AB  - The effect of Cinnamomum zeylanicum essential oil (CZEO) at two concentrations
      (0.02% and 0.04% v/w) on chemical composition, pH, water activity (aw), lipid
      oxidation, color stability and sensory characteristics of Lyoner-type sausage
      stored at 4 C for 40 days was investigated. The moisture content of the control
      sample was higher (p < 0.05) than CZEO incorporated samples, while fat, ash and
      protein content were not affected by adding essential oil. At days 0 and 40,
      Lightness (L*) and whiteness index (WI) were significantly decreased and total
      color difference (DeltaE) significantly increased (p < 0.05) by adding CZEO. With
      the exception of first day of storage, redness (a*) and yellowness (b*) were
      significantly increased and decreased, respectively during the rest of storage (p
      < 0.05). The pH values were not differing between the control samples and samples
      containing CZEO (p > 0.05). The water activity content fell in Lyoners with added
      CZEO during the storage. Incorporation of CZEO retard lipid oxidation process at
      the end of storage (p < 0.05). Samples containing highest amount of CZEO had
      higher sensory score compared to control sample. Our results pointed out that
      CZEO could be used as natural additive for increasing the chemical stability of
      Lyoner-type sausages. 

PMID- 25992250
TI  - Digestion kinetics of carbohydrate fractions of citrus by-products.
AB  - The present experiment was carried out to determine the digestion kinetics of
      carbohydrate fractions of citrus by-products. Grapefruit pulp (GP), lemon pulp
      (LE), lime pulp (LI) and orange pulp (OP) were the test feed. Digestion kinetic
      of whole citrus by-products and neutral detergent fiber (NDF) fraction and acid
      detergent fiber (ADF) fractions of citrus by-products were measured using the in
      vitro gas production technique. Fermentation kinetics of the neutral detergent
      soluble carbohydrates (NDSC) fraction and hemicelluloses were calculated using a
      curve subtraction. The fermentation rate of whole was the highest for the LE (p <
      0.05). For all citrus by-products lag time was longer for hemicellulose than
      other carbohydrate fractions. There was no significant difference among potential
      gas production (A) volumes of whole test feeds (p < 0.16). Dry matter (DM)
      digestibility contents of LE and LI were the highest (p < 0.02). The NDF
      digestibility was the highest (p < 0.05) in LI and GP, while the lowest (p <
      0.03) values of ADF digestibility were observed in LI and LE. According to the
      results of the present study, carbohydrate fractions of citrus by-products have
      high potential for degradability. It could also be concluded that carbohydrate
      fractions of citrus by-products have remarkable difference in digestion kinetics
      and digestive behavior. 

PMID- 25992251
TI  - Stereological estimation and morphological assessment of the endocrine pancreatic
      components in relation to sex in hen.
AB  - In pancreatic survey, quantitative and morphological characteristics could be
      fundamental variables for the evaluation of some structures. The aim of this
      study was the application of stereological methods for estimation of quantitative
      parameters and morphological evaluation of the pancreas in chickens. Ten adult
      male and ten adult female native chickens were used in this study. Routine tissue
      processing was carried out for all samples. The sections were stained with
      hematoxylin and eosin and Gomori's aldehyde-fuchsin. Stereological examinations
      were performed according to systemic uniform random sampling as well as Cavalieri
      and point counting method. The morphological results showed that in both sexes,
      pancreas of chickens was composed of four main pancreatic lobes and contained two
      distinct islet types. Alpha islets consisted of alpha and a few delta cells and
      beta islets contained beta and seldom delta cells. Stereological results showed
      that in both sexes, there were significantly distinctive regional differences in
      the volume of islet and the numerical density of cells among some lobes with
      highest values in third and splenic lobes, respectively (p < 0.05). The nuclear
      volume was lowest in ventral lobe either males (80.60 +/- 33.50) or females
      (84.20 +/- 44.10). Beside, in the islets diameter of splenic lobe, there were
      significant differences in males as compared with females (p < 0.05). In splenic
      lobe, a significant difference was observed in the nuclear diameter in males than
      to females (p < 0.05). The results indicated that although there were not
      morphological changes between sexes in pancreatic lobes, however, some
      stereological parameters could be affected by sex. 

PMID- 25992252
TI  - Protective effects of cornus mas extract on in vitro fertilization potential in
      methotrexate treated male mice.
AB  - Current study was aimed to evaluating protective effects of cornus mas fruit
      extract (CMFE) in mice treated with methotrexate (MTX). For this purpose, 48
      young mature male mice were divided into 6 groups. Control group received only
      normal saline (0.1 mL per day, intraperitoneally), and the second group was
      administered MTX (20 mg kg(-1) per week, intraperitoneally). The third, fourth
      and fifth groups received MTX daily oral doses of 250, 500 and 1000 mg kg(-1)
      CMFE as well as MTX. The sixth group was only given CMFE with a dose of 1000 mg
      kg(-1) per day, orally, for 35 days. Then, the animals were anesthetically
      euthanized and the sperms were separated from epididymis. DNA damage level, the
      amount of malondialdehyde (MDA) as well as in vitro fertility was evaluated. The
      number of sperms with damaged DNA and MDA level in MTX-treated group showed a
      significant increase compared to control group (p < 0.05). In groups receiving
      CMFE along with MTX, DNA damage level and MDA amount suggested a decrease in
      comparison with MTX group (p < 0.05). Also, in vitro fertilization and embryonic
      development in MTX-treated group was significantly lower than the control group,
      and the level of embryonic arresting was higher (p < 0.05). In groups which
      received CMFE along with MTX, in vitro fertility and embryonic development was
      higher than MTX group (p < 0.05) and the arrested embryos showed a decrease. This
      study suggested that cornus mas is able to ameliorate the side effects of MTX. 

PMID- 25992253
TI  - Effect of dietary aloe vera on growth and lipid peroxidation indices in rainbow
      trout (Oncorhynchus mykiss).
AB  - Aloe vera has been used worldwide in pharmaceutical, food and cosmetic industries
      due to the plethora of biological activities of its constituents. This study was
      done to evaluate the effects of dietary aloe vera on growth and lipid
      peroxidation in rainbow trout (Oncorhynchus mykiss). A total number of 480 O.
      mykiss (mean weight 9.50 +/- 0.85 g) were randomized into four experimental
      groups including one control and three experimental groups that aloe vera was
      incorporated in their diet at 0.5, 1.0 and 2.0 g kg(-1). Trial was done for eight
      weeks. Then biometry and blood sampling were done. Plasma malondialdehyde, ferric
      reducing ability of plasma and growth index were estimated at the end of study.
      The results showed that aloe vera extract did not affect growth indices.
      Malondialdehyde was increased in the experimental group compared to the control
      group but ferric reducing ability of plasma showed a decrease in experimental
      groups (p < 0.05) compared to the control group. Our findings showed that dietary
      aloe vera have adverse effects on antioxidant defense system in O. mykiss. 

PMID- 25992254
TI  - Histomorphometric changes of small intestine in pregnant rat.
AB  - Food intake of rats increases during pregnancy. This requires changes in the
      structure of the small intestine to absorb additional food. The aim of the
      present study was to investigate the morphological changes in the layers of small
      intestine in rats during pregnancy. Duodenum, jejunum and ileum of 18 pregnant
      Sprague-Dawley rats (day 7, 14 and 21 of pregnancy) were collected. Villous
      height and width and thickness of lamina propria, tunica muscularis entirely and
      separately (circular and longitudinal layers) were measured on transverse
      sections. During pregnancy increasing villi length and muscular layer thickness
      was observed in duodenum. Furthermore, along with the progress of gestation
      greatest histomorphometric change in small intestine was observed in the jejunum.
      The reduction in the ileum histomorphologic indices was observed during
      pregnancy. In conclusion, increase in histomorphologic indices of duodenum and
      jejunum supplies more capacity of duodenum to digest food intake during pregnancy
      and decrease in these indices in ileum controls the absorption of excess produced
      amino acids and glucose by hyperphagia. 

PMID- 25992255
TI  - Survey of parasitic fauna of different ornamental freshwater fish species in
      Iran.
AB  - Parasitic diseases are harmful and limiting factors in breeding and rearing
      ornamental fish industry. In this study, 400 apparently healthy ornamental fishes
      from five species (each species 80 specimens) including: Goldfish (Carassius
      auratus), guppy (Poecilia reticulate), angelfish (Pterophyllum scalare), discus
      (Symphsodon discus) and sailfin mollies (Poecilia latipinna) was obtained from a
      local ornamental fish farm in the north of Iran during 2011 to 2012. The primary
      purpose of this study was to determine the parasitic infections of aquarium fish
      in Iran. For this purpose, fish were first examined for ectoparasites using wet
      mount under a light microscope. Then, the alimentary ducts of fish were observed
      under light and stereo microscope. In survey of different infection rates for
      different parasitic infections in examining fish: Dactylogyrus sp., Gyrodactylus
      sp., Ichthyophthirius multifiliis Trichodina reticulata, Capillaria sp. and
      Lernaea cyprinacea were collected from five species. All five fish species had
      Monogenea (Gyrodactylidae and Dactylogyridae) in their skins and gills, the
      highest prevalence was observed in C. auratus and the lowest was in P. scalare
      and S. discus. Also, Capillaria sp. was reported as a first record from the
      abdominal cavity of P. scalare in Iran. Our findings revealed that the protozoal
      infections are very common among aquarium fishes. Although, no gross pathology
      was observed among infected fishes, but it is likely that in case of any changes
      in the environment, then parasitic infections could be harmful. 

PMID- 25992256
TI  - Risk factors affecting chemical and bacteriological quality of bulk tank milk in
      Kerman, Iran.
AB  - Milk is often described as a complete food because it contains protein, sugar,
      fat, vitamins, and minerals. This study was performed to investigate risk factors
      affecting chemical and bacteriological quality of bulk tank milk. According to
      the following conducted experiments, the milk was divided into two standard and
      non-standard groups. Then, effect of risk factors on making the samples non
      standard was studied. Risk factors such as type of milk delivery unit, distance
      of cattle farm from plant, size of herd, education level of stockbreeders,
      capacity of milk transport tank, capacity of cooler device, and number of workers
      employed in cattle farms were evaluated in this study. Microbial and chemical
      evaluations were performed. Beta-lactam antibiotic residues and somatic cell
      count were specified. At the same time, the stockbreeders who referred to the
      plant were given some questionnaires and the mentioned primary questions were
      asked. After collecting the data, logistic regression model was used. According
      to the obtained results and comparison with Iran's national standard, 26 out of
      109 samples were determined to be at standard level and 83 ones had at least one
      out-of-standard factor. The results obtained from the model demonstrated
      significant effect of education of stockbreeders and capacity of cooler devices
      on the milk quality. Education of stockbreeders could greatly affect management
      of a cattle farm unit. 

PMID- 25992257
TI  - Molecular characterization of a new microvariant of the G3 genotype for
      Echinococcus granulosus in water buffalo in Iran.
AB  - In this study, molecular characterization of Echinococcus granulosus sample
      obtained from water buffalo originating from southwest of Iran was performed
      using comparative sequence analysis of cox1 mitochondrial gene. DNA was extracted
      from protoscoleces removed from hydatid cyst from the liver of a 2-year-old male
      buffalo slaughtered in Khuzestan province. Molecular and phylogenetic analyses
      were conducted based on cox1 mitochondrial gene. We found the presence of a new
      microvariant of G3 genotype for E. granulosus in Iran which is genetically
      differentiated from reference G3 sequence (M84663). The difference was a
      transition mutation of adenine to guanine in position 214 (A214G) resulting in a
      substitution of the threonine (ACT) by alanine (GCT). These findings extend the
      knowledge of heterogeneity and distribution of G3 genotype for E. granulosus in
      world. 

PMID- 25992258
TI  - Concurrent atypical diffused tuberculosis and macrorhabdosis in a canary (Serinus
      canaria).
AB  - A dead canary from a mixed species zoological garden was presented for diagnostic
      necropsy. Cachexia with prominent atrophy of pectoral muscles, yellowish brown
      discoloration of the liver and kidney, dark brown to black intestinal contents
      and moderate proventricular dilatation with some degree of catarrhal gastritis
      were the significant macroscopic findings. Parenchymatous organs like the liver,
      the spleen, the lung and the kidneys were extremely affected by massive diffuse
      necrosis and heavy infiltration of mononuclear inflammatory cells,
      histopathologically. Many giant bacilli resembling Macrorrhabdus ornithogaster
      were seen microscopically in the wet smear of the isthmus mucosa. Ghost-like
      unstained bacilli were revealed in the Giemsa stained contact smears of the liver
      and spleen. No typical mycobacterial granulomatous lesion was found in different
      tissues, but in Ziehl-Neelsen stained thin layer histologic sections from the
      liver, spleen, lung and kidney, numerous acid fast organisms were diffusely
      distributed. The case was diagnosed an atypical avian tuberculosis with
      concurrent macrorhabdosis. Mycobacterium sp. are capable of giving rise to a
      progressive disease in humans, especially in immunocompromised individuals. Cases
      of avian tuberculosis might be overlooked for lack of pathognomonic lesions
      suggestive of mycobacteriosis. 

PMID- 25992259
TI  - Adenovirus-like inclusion body hepatitis in a flock of broiler chickens in
      Kermanshah province, Iran.
AB  - Inclusion body hepatitis (IBH) has been reported in many countries in the world.
      The IBH or similar cases characterized by hepatitis and presence of intra-nuclear
      inclusion bodies in hepatocytes have not been reported in broiler chickens in
      Iran. This is the first report on outbreak of adenovirus-like inclusion body
      hepatitis in Iran. On October 2012, an onset of high acute mortality in a flock
      of 2 day-old broiler chickens was reported to the Veterinary Clinic, Faculty of
      Veterinary Medicine, Razi University, Kermanshah, Iran. The birds showed
      lethargy, huddling, ruffled feathers, and inappetence. At necropsy the livers
      were the primary organ affected which were enlarged, pale yellow with necrotic
      foci and multiple petechial hemorrhages. Tissue samples of liver, kidneys and
      heart were fixed in 10% buffered formalin. They were processed and stained with
      hematoxylin and eosin for histopathological studies. Significant microscopic
      lesions were seen in the livers. Large eosinophilic intra-nuclear inclusion
      bodies were seen in hepatocytes. Based on the acute high mortality, age of the
      broilers, gross lesions and histopathological findings (especially intra-nuclear
      inclusion bodies), the condition was diagnosed as adenovirus-like inclusion body
      hepatitis. 

PMID- 25992260
TI  - CEREC CAD/CAM Chairside System.
AB  - PURPOSE: The aim of this paper was to describe the CEREC 3 chairside system,
      providing the clinicians a detailed analysis of the whole digital workflow.
      Benefits and limitations of this technology compared with the conventional
      prosthetic work-flow were also highlighted and discussed. MATERIALS AND METHODS:
      Clinical procedures (tooth preparation, impression taking, adhesive luting),
      operational components and their capabilities as well as restorative materials
      used with CEREC 3 chairside system were reported. RESULTS: The CEREC system has
      shown many positive aspects that make easier, faster and less expensive the
      prosthetic workflow. The operator-dependent errors are minimized compared to the
      conventional prosthetic protocol. Furthermore, a better acceptance level for the
      impression procedure has shown by the patients. The only drawback could be the
      subgingival placement of the margins compared with the supra/juxta gingival
      margins, since more time was required for the impression taking as well as the
      adhesive luting phase. The biocopy project seemed to be the best tool to obtain
      functionalized surfaces and keep unchanged gnathological data. Material selection
      was related to type of restoration. CONCLUSIONS: The evidence of our clinical
      practice suggests that CEREC 3 chairside system allows to produce highly
      aesthetic and reliable restorations in a single visit, while minimizing costs and
      patient discomfort during prosthetic treatment. However improvements in materials
      and technologies are needed in order to overcome the actual drawbacks.

PMID- 25992262
TI  - Simplified type 3 implant placement, after alveolar ridge preservation: a case
      study.
AB  - Alveolar ridge, after tooth extraction, could reduce its volume up to 50% in
      buccal-lingual width in the first twelve months and residual dimensions could
      interfere with correct three dimensional placement of implants and influence
      negatively treatment outcomes with regard to function and aesthetic aspects. Over
      the last decades, several approaches have been proposed and tested in order to
      prevent ridge volumetric contraction and provide maximum bone availability for
      implant procedure. This article presents a case study with a single anterior
      tooth replacement, illustrating socket seal technique followed by a type 3 timing
      implant placement. Immediately after tooth extraction, residual socket was
      grafted using Deproteinized Bovine Bone Mineral and a free gingival punch
      harvested from palate. After 3 months, a root-form titanium implant was inserted
      without additional regenerative procedures. Follow-up examination revealed
      favourable preservation of soft tissue width and height in the aesthetic area.
      Socket seal approach maximizes soft tissue healing, preserving ridge envelope and
      the subsequent implant placement, furthermore, results simplified, as any
      augmentation techniques are required. Clinical advantages of this method include
      predictable preservation of the soft tissues, favourable healing features, easy
      handling of graft materials and a positive benefit-cost ratio. 

PMID- 25992261
TI  - The effects of host derived metalloproteinases on dentin bond and the role of
      MMPs inhibitors on dentin matrix degradation.
AB  - OBJECTIVES: The work has the objective to analyze the literature on the
      degradation of the adhesive interface. In particular the study is focused on the
      role of the metalloproteinase in the hydrolytic degradation of collagen matrix in
      the bonded interface. The survey will concern also the latest innovations to
      improve and increase the link between dentin and the restorative materials
      through the MMPs inhibitors. METHODS: The research has been carried out in the
      MEDLINE database by choosing keywords as "metalloproteinases" and "dentin bond"
      and "degradation". In vitro studies were included in the research, excluding
      studies with no human and deciduous teeth. Language was limited to English.
      RESULTS: The collagenolytic enzymes in mineralized dentin have been demonstrated
      to have an important role in dental hard tissue pathologies, including the
      degradation of the hybrid layer. CONCLUSION: The preservation of the collagen
      matrix integrity is a key issue in the attempts to improve the dentin bonding
      durability.

PMID- 25992263
TI  - Palatal obturators in patients after maxillectomy.
AB  - Prosthodontic management of palatal defects is fundamental to improve patient's
      life undergoing to a maxillary surgical treatment. A lot of maxillary defects are
      a direct consequence of surgical treatment of malformations, neoplasms or trauma.
      The obturators are prosthesis used to close palatal defects after maxillectomy,
      to restore masticatory function and to improve speech. The primary goals of the
      obturator prosthesis are to preserve the remaining teeth and tissue and to
      provide comfort, function, and aesthetics to the patients. Different materials
      and retention methods are a characteristic of new types of obturators. 

PMID- 25992265
TI  - Sequential pattern mining for discovering gene interactions and their contextual
      information from biomedical texts.
AB  - BACKGROUND: Discovering gene interactions and their characterizations from
      biological text collections is a crucial issue in bioinformatics. Indeed, text
      collections are large and it is very difficult for biologists to fully take
      benefit from this amount of knowledge. Natural Language Processing (NLP) methods
      have been applied to extract background knowledge from biomedical texts. Some of
      existing NLP approaches are based on handcrafted rules and thus are time
      consuming and often devoted to a specific corpus. Machine learning based NLP
      methods, give good results but generate outcomes that are not really
      understandable by a user. RESULTS: We take advantage of an hybridization of data
      mining and natural language processing to propose an original symbolic method to
      automatically produce patterns conveying gene interactions and their
      characterizations. Therefore, our method not only allows gene interactions but
      also semantics information on the extracted interactions (e.g., modalities,
      biological contexts, interaction types) to be detected. Only limited resource is
      required: the text collection that is used as a training corpus. Our approach
      gives results comparable to the results given by state-of-the-art methods and is
      even better for the gene interaction detection in AIMed. CONCLUSIONS: Experiments
      show how our approach enables to discover interactions and their
      characterizations. To the best of our knowledge, there is few methods that
      automatically extract the interactions and also associated semantics information.
      The extracted gene interactions from PubMed are available through a simple web
      interface at https://bingotexte.greyc.fr/. The software is available at
      https://bingo2.greyc.fr/?q=node/22.

PMID- 25992264
TI  - Networks of neuroinjury semantic predications to identify biomarkers for mild
      traumatic brain injury.
AB  - OBJECTIVE: Mild traumatic brain injury (mTBI) has high prevalence in the
      military, among athletes, and in the general population worldwide (largely due to
      falls). Consequences can include a range of neuropsychological disorders.
      Unfortunately, such neural injury often goes undiagnosed due to the difficulty in
      identifying symptoms, so the discovery of an effective biomarker would greatly
      assist diagnosis; however, no single biomarker has been identified. We identify
      several body substances as potential components of a panel of biomarkers to
      support the diagnosis of mild traumatic brain injury. METHODS: Our approach to
      diagnostic biomarker discovery combines ideas and techniques from systems
      medicine, natural language processing, and graph theory. We create a molecular
      interaction network that represents neural injury and is composed of
      relationships automatically extracted from the literature. We retrieve citations
      related to neurological injury and extract relationships (semantic predications)
      that contain potential biomarkers. After linking all relationships together to
      create a network representing neural injury, we filter the network by
      relationship frequency and concept connectivity to reduce the set to a manageable
      size of higher interest substances. RESULTS: 99,437 relevant citations yielded
      26,441 unique relations. 18,085 of these contained a potential biomarker as
      subject or object with a total of 6246 unique concepts. After filtering by graph
      metrics, the set was reduced to 1021 relationships with 49 unique concepts,
      including 17 potential biomarkers. CONCLUSION: We created a network of
      relationships containing substances derived from 99,437 citations and filtered
      using graph metrics to provide a set of 17 potential biomarkers. We discuss the
      interaction of several of these (glutamate, glucose, and lactate) as the basis
      for more effective diagnosis than is currently possible. This method provides an
      opportunity to focus the effort of wet bench research on those substances with
      the highest potential as biomarkers for mTBI.

PMID- 25992266
TI  - The rise and rise of Pulmonary Circulation.

PMID- 25992267
TI  - The right ventricle in scleroderma (2013 Grover Conference Series).
AB  - Pulmonary arterial hypertension (PAH) results from severe remodeling of the
      distal lung vessels leading irremediably to death through right ventricular (RV)
      failure. PAH (Group 1 of the World Health Organization classification of
      pulmonary hypertension) can be idiopathic (IPAH) or associated with other
      disorders, such as connective tissue diseases. Prominent among the latter is
      systemic sclerosis (SSc), a heterogeneous disorder characterized by endothelium
      dysfunction, dysregulation of fibroblasts resulting in excessive collagen
      production, and immune abnormalities. For as-yet-unknown reasons, SSc-associated
      PAH (SSc-PAH) carries a significantly worse prognosis compared with any other
      form of PAH in Group 1, including IPAH. We have previously shown that patients
      with SSc-PAH have a median survival of only 3 years, compared with 8 years for
      IPAH, despite modern PAH therapy. Because death is principally due to RV failure,
      we speculated that RV adaptation to PAH differed between the two entities due to
      disparate pulmonary artery loading, perhaps from vessel stiffening, or intrinsic
      RV myocardial disease that might limit function and adaptation to high afterload.
      In SSc, RV function may also be impaired by inflammatory processes, excess
      fibrosis of the myocardium, or altered angiogenesis, which may all contribute to
      impaired contractile reserve exacerbating cardiopulmonary impedance mismatch.
      This is now suggested by recent findings from our group that demonstrate that,
      although pulmonary vascular load may be similar between patients with IPAH and
      those with SSc-PAH, the latter display reduced myocardial contractility as
      assessed by pressure-volume loop measurements. This review focuses on fundamental
      hemodynamic, structural, and functional differences in RV from patients with SSc
      PAH compared with IPAH, which may account for survival discrepancies between the
      two populations. Possible underlying basic mechanisms are discussed. 

PMID- 25992268
TI  - Cardiac energy metabolic alterations in pressure overload-induced left and right
      heart failure (2013 Grover Conference Series).
AB  - Pressure overload of the heart, such as seen with pulmonary hypertension and/or
      systemic hypertension, can result in cardiac hypertrophy and the eventual
      development of heart failure. The development of hypertrophy and heart failure is
      accompanied by numerous molecular changes in the heart, including alterations in
      cardiac energy metabolism. Under normal conditions, the high energy (adenosine
      triphosphate [ATP]) demands of the heart are primarily provided by the
      mitochondrial oxidation of fatty acids, carbohydrates (glucose and lactate), and
      ketones. In contrast, the hypertrophied failing heart is energy deficient because
      of its inability to produce adequate amounts of ATP. This can be attributed to a
      reduction in mitochondrial oxidative metabolism, with the heart becoming more
      reliant on glycolysis as a source of ATP production. If glycolysis is uncoupled
      from glucose oxidation, a decrease in cardiac efficiency can occur, which can
      contribute to the severity of heart failure due to pressure-overload hypertrophy.
      These metabolic changes are accompanied by alterations in the enzymes that are
      involved in the regulation of fatty acid and carbohydrate metabolism. It is now
      becoming clear that optimizing both energy production and the source of energy
      production are potential targets for pharmacological intervention aimed at
      improving cardiac function in the hypertrophied failing heart. In this review, we
      will focus on what alterations in energy metabolism occur in pressure overload
      induced left and right heart failure. We will also discuss potential targets and
      pharmacological approaches that can be used to treat heart failure occurring
      secondary to pulmonary hypertension and/or systemic hypertension. 

PMID- 25992269
TI  - The right ventricle under pressure: evaluating the adaptive and maladaptive
      changes in the right ventricle in pulmonary arterial hypertension using
      echocardiography (2013 Grover Conference series).
AB  - The importance of the right ventricle (RV) in pulmonary arterial hypertension
      (PAH) has been gaining increased recognition. This has included a
      reconceptualization of the RV as part of an RV-pulmonary circulation interrelated
      unit and the observation that RV function is a major determinant of prognosis in
      PAH. Noninvasive imaging of RV size and function is critical to the longitudinal
      management of patients with PAH, and continued understanding of the
      pathophysiology of pulmonary vascular disease relies on the response of the RV to
      pulmonary vascular remodeling. Echocardiography, in particular the newer
      echocardiographic measurements and techniques, allows easy, readily accessible
      means to assess and follow RV size and function. 

PMID- 25992270
TI  - Neonatal oxygenation, pulmonary hypertension, and evolutionary adaptation to high
      altitude (2013 Grover Conference series).
AB  - Andeans and Tibetans have less altitude reduction in birth weight than do shorter
      resident groups, but only Tibetans are protected from pulmonary hypertension and
      chronic mountain sickness (CMS). We hypothesized that differences in neonatal
      oxygenation were involved, with arterial O2 saturation (SaO2) being highest in
      Tibetans, intermediate in Andeans, and lowest in Han or Europeans, and that
      improved oxygenation in Andeans relative to Europeans was accompanied by a
      greater postnatal decline in systolic pulmonary arterial pressures (Ppasys ). We
      studied 41 healthy (36 Andeans, 5 Europeans) and 9 sick infants at 3,600 m in
      Bolivia. The SaO2 in healthy babies was highest at 6-24 hours of postnatal age
      and then declined, whereas sick babies showed the opposite pattern. Compared to
      that of 30 Tibetan or Han infants studied previously at 3,600 m, SaO2 was higher
      in Tibetans than in Han or Andeans during wakefulness and active or quiet sleep.
      Tibetans, as well as Andeans, had higher values than Han while feeding. The
      SaO2's of healthy Andeans and Europeans were similar and, like those of Tibetans,
      remained at 85% or above, whereas Han values dipped below 70%. Andean and
      European Ppasys values were above sea-level norms and higher in sick than in
      healthy babies, but right heart pressure decreased across 4-6 months in all
      groups. We concluded that Tibetans had better neonatal oxygenation than Andeans
      at 3,600 m but that, counter to our hypothesis, neither was SaO2 higher nor Ppa
      lower in Andean than in European infants. Further, longitudinal studies in these
      4 groups are warranted to determine whether neonatal oxygenation influences
      susceptibility to high-altitude pulmonary hypertension and CMS later in life. 

PMID- 25992272
TI  - Stem and progenitor cell therapy for pulmonary arterial hypertension: effects on
      the right ventricle (2013 Grover Conference Series).
AB  - In experimental animals and in patients with pulmonary arterial hypertension
      (PAH), a wide spectrum of structural and functional conditions is known that may
      be responsible for the switch of a state of "compensated" right ventricular (RV)
      hypertrophy to a state of RV failure. In recent years, therapy with
      differentiated cells, endothelial progenitor cells, and mesenchymal stem cells
      has been shown to cause partial or complete reversal of pathological
      characteristics of PAH. The therapeutic effects of stem or progenitor cell
      therapy are considered to be (1) paracrine effects from stem or progenitor cells
      that had engrafted in the myocardium (or elsewhere), by compounds that have anti
      inflammatory, antiapoptotic, and proangiogenic actions and (2) unloading effects
      on the right ventricle due to stem or progenitor cell-induced decrease in
      pulmonary vascular resistance and decrease in pulmonary artery pressure. 

PMID- 25992273
TI  - The need to recognize the pulmonary circulation and the right ventricle as an
      integrated functional unit: facts and hypotheses (2013 Grover Conference series).
AB  - For many patients with severe pulmonary arterial hypertension, heart failure-and,
      in particular, right heart failure-is the final chapter of their chronic illness.
      Targeted therapy for pulmonary hypertension is effective only if the right
      ventricular ejection fraction is maintained or improved. Because improvement of
      right heart function and reversal of right heart failure are treatment goals, it
      is important to investigate the cellular and molecular mechanisms that cause
      right heart failure. Here, we propose that right ventricular capillary
      rarefaction is an important hallmark of right heart failure and consider that the
      "sick lung circulation" and the pressure-overloaded right ventricle constitute a
      functional unit. 

PMID- 25992271
TI  - Emerging roles for histone deacetylases in pulmonary hypertension and right
      ventricular remodeling (2013 Grover Conference series).
AB  - Reversible lysine acetylation has emerged as a critical mechanism for controlling
      the function of nucleosomal histones as well as diverse nonhistone proteins.
      Acetyl groups are conjugated to lysine residues in proteins by histone
      acetyltransferases and removed by histone deacetylases (HDACs), which are also
      commonly referred to as lysine deacetylases. Over the past decade, many studies
      have shown that HDACs play crucial roles in the control of left ventricular (LV)
      cardiac remodeling in response to stress. Small molecule HDAC inhibitors block
      pathological hypertrophy and fibrosis and improve cardiac function in various
      preclinical models of LV failure. Only recently have HDACs been studied in the
      context of right ventricular (RV) failure, which commonly occurs in patients who
      experience pulmonary hypertension (PH). Here, we review recent findings with HDAC
      inhibitors in models of PH and RV remodeling, propose next steps for this newly
      uncovered area of research, and highlight potential for isoform-selective HDAC
      inhibitors for the treatment of PH and RV failure. 

PMID- 25992274
TI  - The role of wall shear stress in the assessment of right ventricle hydraulic
      workload.
AB  - Pulmonary hypertension (PH) is a devastating disease affecting approximately 15
      50 people per million, with a higher incidence in women. PH mortality is mostly
      attributed to right ventricle (RV) failure, which results from RV hypotrophy due
      to an overburdened hydraulic workload. The objective of this study is to
      correlate wall shear stress (WSS) with hemodynamic metrics that are generally
      accepted as clinical indicators of RV workload and are well correlated with
      disease outcome. Retrospective right heart catheterization data for 20 PH
      patients were analyzed to derive pulmonary vascular resistance (PVR), arterial
      compliance (C), and an index of wave reflections (Gamma). Patient-specific
      contrast-enhanced computed tomography chest images were used to reconstruct the
      individual pulmonary arterial trees up to the seventh generation. Computational
      fluid dynamics analyses simulating blood flow at peak systole were conducted for
      each vascular model to calculate WSS distributions on the endothelial surface of
      the pulmonary arteries. WSS was found to be decreased proportionally with
      elevated PVR and reduced C. Spatially averaged WSS (SAWSS) was positively
      correlated with PVR (R (2) = 0.66), C (R (2) = 0.73), and Gamma (R (2) = 0.5) and
      also showed promising preliminary correlations with RV geometric characteristics.
      Evaluating WSS at random cross sections in the proximal vasculature (main, right,
      and left pulmonary arteries), the type of data that can be acquired from phase
      contrast magnetic resonance imaging, did not reveal the same correlations. In
      conclusion, we found that WSS has the potential to be a viable and clinically
      useful noninvasive metric of PH disease progression and RV health. Future work
      should be focused on evaluating whether SAWSS has prognostic value in the
      management of PH and whether it can be used as a rapid reactivity assessment
      tool, which would aid in selection of appropriate therapies. 

PMID- 25992275
TI  - Vascular endothelial growth factor receptor 3 signaling contributes to
      angioobliterative pulmonary hypertension.
AB  - The mechanisms involved in the development of severe angioobliterative pulmonary
      arterial hypertension (PAH) are multicellular and complex. Many of the features
      of human severe PAH, including angioobliteration, lung perivascular inflammation,
      and right heart failure, are reproduced in the Sugen 5416/chronic hypoxia (SuHx)
      rat model. Here we address, at first glance, the confusing and paradoxical aspect
      of the model, namely, that treatment of rats with the antiangiogenic vascular
      endothelial growth factor (VEGF) receptor 1 and 2 kinase inhibitor, Sugen 5416,
      when combined with chronic hypoxia, causes angioproliferative pulmonary vascular
      disease. We postulated that signaling through the unblocked VEGF receptor VEGFR3
      (or flt4) could account for some of the pulmonary arteriolar lumen-occluding cell
      growth. We also considered that Sugen 5416-induced VEGFR1 and VEGFR2 blockade
      could alter the expression pattern of VEGF isoform proteins. Indeed, in the lungs
      of SuHx rats we found increased expression of the ligand proteins VEGF-C and VEGF
      D as well as enhanced expression of the VEGFR3 protein. In contrast, in the
      failing right ventricle of SuHx rats there was a profound decrease in the
      expression of VEGF-B and VEGF-D in addition to the previously described reduction
      in VEGF-A expression. MAZ51, an inhibitor of VEGFR3 phosphorylation and VEGFR3
      signaling, largely prevented the development of angioobliteration in the SuHx
      model; however, obliterated vessels did not reopen when animals with established
      PAH were treated with the VEGFR3 inhibitor. Part of the mechanism of
      vasoobliteration in the SuHx model occurs via VEGFR3. VEGFR1/VEGFR2 inhibition
      can be initially antiangiogenic by inducing lung vessel endothelial cell
      apoptosis; however, it can be subsequently angiogenic via VEGF-C and VEGF-D
      signaling through VEGFR3. 

PMID- 25992276
TI  - Impact of diabetes in patients with pulmonary hypertension.
AB  - Diabetes complicates management in a number of disease states and adversely
      impacts survival; how diabetes affects patients with pulmonary hypertension (PH)
      has not been well characterized. With insulin resistance having recently been
      demonstrated in PH, we sought to examine the impact of diabetes in these
      patients. Demographic characteristics, echo data, and invasive hemodynamic data
      were prospectively collected for 261 patients with PH referred for initial
      hemodynamic assessment. Diabetes was defined as documented insulin resistance or
      treatment with antidiabetic medications. Fifty-five patients (21%) had diabetes,
      and compared with nondiabetic patients, they were older (mean years +/- SD, 61 +/
      13 vs. 56 +/- 16; [Formula: see text]), more likely to be black (29% vs. 14%;
      [Formula: see text]) and hypertensive (71% vs. 30%; [Formula: see text]), and had
      higher mean (+/-SD) serum creatinine levels (1.1 +/- 0.5 vs. 1.0 +/- 0.4;
      [Formula: see text]). Diabetic patients had similar World Health Organization
      functional class at presentation but were more likely to have pulmonary venous
      etiology of PH (24% vs. 10%; [Formula: see text]). Echo findings, including
      biventricular function, tricuspid regurgitation, and pressure estimates were
      similar. Invasive pulmonary pressures and cardiac output were similar, but right
      atrial pressure was appreciably higher (14 +/- 8 mmHg vs. 10 +/- 5 mmHg;
      [Formula: see text]). Despite similar management, survival was markedly worse and
      remained so after statistical adjustment. In summary, diabetic patients referred
      for assessment of PH were more likely to have pulmonary venous disease than
      nondiabetic patients with PH, with hemodynamics suggesting greater right-sided
      diastolic dysfunction. The markedly worse survival in these patients merits
      further study. 

PMID- 25992277
TI  - Arginine metabolic endotypes in pulmonary arterial hypertension.
AB  - Decreased synthesis of nitric oxide (NO) by NO synthases (NOS) is believed to
      play an important role in the pathogenesis of pulmonary arterial hypertension
      (PAH). Multiple factors may contribute to decreased NO bioavailability, including
      increased activity of arginase, the enzyme that converts arginine to ornithine
      and urea, which may compete with NOS for arginine; inadequate de novo arginine
      production from citrulline; and increased concentration of asymmetric
      dimethylarginine (ADMA), an endogenous inhibitor of NOS. We hypothesized that PAH
      patients with the lowest arginine availability secondary to increased arginase
      activity and/or inadequate de novo arginine synthesis might have a slower rate of
      NO synthesis and greater pulmonary vascular resistance. Nine patients with group
      1 PAH and 10 healthy controls were given primed, constant intravenous infusions
      of (15)N2-arginine, (13)C,(2)H4-citrulline, (15)N2-ornithine, and (13)C-urea in
      the postabsorptive state. The results showed that, compared with healthy
      controls, PAH patients had a tendency toward increased arginine clearance and
      ornithine flux but no difference in arginine and citrulline flux, de novo
      arginine synthesis, or NO synthesis. Arginine-to-ADMA ratio was increased in PAH
      patients. Two endotypes of patients with low and high arginase activity were
      identified; compared with the low-arginase group, the patients with high arginase
      had increased arginine flux, slower NO synthesis, and lower plasma concentrations
      of ADMA. These results demonstrate that increased breakdown of arginine by
      arginase occurs in PAH and affects NO synthesis. Furthermore, there is no
      compensatory increase in de novo arginine synthesis to overcome this increased
      utilization of arginine by arginase. 

PMID- 25992278
TI  - Right ventricular long noncoding RNA expression in human heart failure.
AB  - The expression of long noncoding RNAs (lncRNAs) in human heart failure (HF) has
      not been widely studied. Using RNA sequencing (RNA-Seq), we compared lncRNA
      expression in 22 explanted human HF hearts with lncRNA expression in 5 unused
      donor human hearts. We used Cufflinks to identify isoforms and DESeq to identify
      differentially expressed genes. We identified the noncoding RNAs by cross
      reference to Ensembl release 73 (Genome Reference Consortium human genome build
      37) and explored possible functional roles using a variety of online tools. In HF
      hearts, RNA-Seq identified 84,793 total messenger RNA coding and noncoding
      different transcripts, including 13,019 protein-coding genes, 2,085 total lncRNA
      genes, and 1,064 pseudogenes. By Ensembl noncoding RNA categories, there were 48
      lncRNAs, 27 pseudogenes, and 30 antisense RNAs for a total of 105 differentially
      expressed lncRNAs in HF hearts. Compared with donor hearts, HF hearts exhibited
      differential expression of 7.7% of protein-coding genes, 3.7% of lncRNAs
      (including pseudogenes), and 2.5% of pseudogenes. There were not consistent
      correlations between antisense lncRNAs and parent genes and between pseudogenes
      and parent genes, implying differential regulation of expression. Exploratory in
      silico functional analyses using online tools suggested a variety of possible
      lncRNA regulatory roles. By providing a comprehensive profile of right
      ventricular polyadenylated messenger RNA transcriptome in HF, RNA-Seq provides an
      inventory of differentially expressed lncRNAs, including antisense transcripts
      and pseudogenes, for future mechanistic study. 

PMID- 25992279
TI  - Acute hemodynamic effects of nebulized iloprost via the I-neb Adaptive Aerosol
      Delivery system in pulmonary hypertension.
AB  - Inhaled iloprost has proven to be an effective therapy in patients with pulmonary
      hypertension (PH). However, the acute hemodynamic effect of nebulized iloprost
      delivered via the I-neb Adaptive Aerosol Delivery (AAD) system remains unclear
      and needs to be assessed. In this study, 126 patients with PH were classified
      according to current guidelines (59, 34, 29, and 4 patients in groups 1/1', 3, 4,
      and 5, respectively; 20 patients had idiopathic pulmonary arterial hypertension
      [iPAH]), were randomly assigned to inhale iloprost 2.5 [Formula: see text]g (n =
      67) or 5.0 [Formula: see text]g (n = 59) via the I-neb AAD system, and were
      assessed by right heart catheterization. In seven patients with iPAH, iloprost
      plasma levels were measured. The two iloprost doses caused decreases from
      baseline in pulmonary vascular resistance (PVR; 2.5 [Formula: see text]g: -14.7%;
      5.0 [Formula: see text]g: -15.6%) and mean pulmonary arterial pressure (mPAP; 2.5
      [Formula: see text]g: -11.0%; 5.0 [Formula: see text]g: -10.1%) while cardiac
      index (CI) increased (2.5 [Formula: see text]g: +6.5%; 5.0 [Formula: see text]g:
      +6.4%). The subset with iPAH also showed decreases from baseline in PVR and mPAP
      and an increase in CI. Peak iloprost plasma levels showed no significant
      difference after inhalation of 2.5 [Formula: see text]g or 5.0 [Formula: see
      text]g iloprost (95.5 pg/mL vs. 73.0 pg/mL; P = 0.06). In summary, nebulized
      iloprost delivered via the I-neb AAD system reduced mPAP and PVR and increased CI
      from baseline in a heterogeneous group of patients with PH and in the subset with
      iPAH. In patients with iPAH, inhalation of 2.5 [Formula: see text]g or 5.0
      [Formula: see text]g iloprost resulted in broadly similar peak iloprost plasma
      levels. 

PMID- 25992280
TI  - Derivation of a screening tool to identify patients with right ventricular
      dysfunction or tricuspid regurgitation after negative computerized tomographic
      pulmonary angiography of the chest.
AB  - Many dyspneic patients who undergo computerized tomographic pulmonary angiography
      (CTPA) for presumed acute pulmonary embolism (PE) have no identified cause for
      their dyspnea yet have persistent symptoms, leading to more CTPA scanning. Right
      ventricular (RV) dysfunction or overload can signal treatable causes of dyspnea.
      We report the rate of isolated RV dysfunction or overload after negative CTPA and
      derive a clinical decision rule (CDR). We performed secondary analysis of a
      multicenter study of diagnostic accuracy for PE. Inclusion required persistent
      dyspnea and no PE. Echocardiography was ordered at clinician discretion. A
      characterization of isolated RV dysfunction or overload required normal left
      ventricular function and RV hypokinesis, or estimated RV systolic pressure of at
      least 40 mmHg. The CDR was derived from bivariate analysis of 97 candidate
      variables, followed by multivariate logistic regression. Of 647 patients, 431 had
      no PE and persistent dyspnea, and 184 (43%) of these 431 had echocardiography
      ordered. Of these, 64 patients (35% [95% confidence interval (CI): 28%-42%]) had
      isolated RV dysfunction or overload, and these patients were significantly more
      likely to have a repeat CTPA within 90 days (P = .02, [Formula: see text] test).
      From univariate analysis, 4 variables predicted isolated RV dysfunction: complete
      right bundle branch block, normal CTPA scan, active malignancy, and CTPA with
      infiltrate, the last negatively. Logistic regression found only normal CTPA
      scanning significant. The final rule (persistent dyspnea + normal CTPA scan) had
      a positive predictive value of 53% (95% CI: 37%-69%). We conclude that a simple
      CDR consisting of persistent dyspnea plus a normal CTPA scan predicts a high
      probability of isolated RV dysfunction or overload on echocardiography. 

PMID- 25992282
TI  - Pulmonary hypertension associated with heart failure with preserved ejection
      fraction: acute hemodynamic effects of inhaled iloprost.
AB  - Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and
      clinical status with minimal systemic adversity in patients with pulmonary
      arterial hypertension. Our single-site, prospective case series aimed to
      determine the effects of iloprost in subjects with group 2 pulmonary hypertension
      and heart failure with preserved ejection fraction. Patients referred to Boston
      Medical Center for initial evaluation of suspected pulmonary hypertension
      received a test dose of 2.5 MUg inhaled iloprost, followed by two subsequent
      doses of 5 MUg. Hemodynamic measurements were recorded for each inhalation after
      15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed
      rank test. Eight subjects fulfilled criteria and elected to enter the study.
      There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg
      [P = 0.005] and 4.7 mmHg [P = 0.021] with the first and second 5-MUg inhalations,
      respectively) and pulmonary vascular resistance (by an average of 161.9
      dyn.s/cm(5) [P = 0.019] and 95.0 dyn.s/cm(5) [P = 0.014] with the first and
      second 5-MUg inhalations, respectively). There were trends for increased cardiac
      output and decreased oxygen saturation. There were no changes in other vital or
      hemodynamic parameters, including pulmonary capillary wedge pressure. All
      patients completed each cycle of iloprost administration without preestablished
      termination criteria. In patients with pulmonary hypertension and heart failure
      with preserved ejection fraction, inhaled iloprost resulted in acute reduction of
      pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation
      of iloprost in this subset of patients is warranted. 

PMID- 25992281
TI  - The sexual dimorphism associated with pulmonary hypertension corresponds to a
      fibrotic phenotype.
AB  - Although female predominance in the development of all types of pulmonary
      hypertension (PH) is well established, many clinical studies have confirmed that
      females have better prognosis and higher survival rate than males. There is no
      clear explanation of why sex influences the pathogenesis and progression of PH.
      Using a rat angioproliferative model of PH, which closely resembles the primary
      pathological changes observed in humans, we evaluated the role of sex in the
      development and progression of PH. Female rats had a more pronounced increase in
      medial thickness in the small pulmonary arteries. However, the infiltration of
      small pulmonary arteries by inflammatory cells was found only in male rats, and
      this corresponded to increased myeloperoxidase activity and abundant adventitial
      and medial fibrosis that were not present in female rats. Although the level of
      right ventricle (RV) peak systolic pressure was similar in both groups, the
      survival rate in male rats was significantly lower. Moreover, male rats presented
      with a more pronounced increase in RV thickness that correlated with diffuse RV
      fibrosis and significantly impaired right cardiac function. The reduction in
      fibrosis in female rats correlated with increased expression of caveolin-1 and
      reduced endothelial nitric oxide synthase-derived superoxide. We conclude that,
      in the pathogenesis of PH, female sex is associated with greater remodeling of
      the pulmonary arteries but greater survival. Conversely, in males, the
      development of pulmonary and cardiac fibrosis leads to early and severe RV
      failure, and this may be an important reason for the lower survival rate among
      males. 

PMID- 25992283
TI  - Peripheral pulmonary artery stenosis as a cause of pulmonary hypertension in
      adults.
AB  - Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in
      the adult population. PPAS can lead to pulmonary hypertension but is likely
      misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic
      thromboembolic pulmonary hypertension. We retrospectively identified adult
      patients with PPAS either in its isolated form or related to other congenital
      defects from January 1998 to September 2012. We reviewed the patients' clinical
      data by using our hospital electronic medical records and/or their paper charts.
      We identified 6 adult patients with PPAS with an age range of 16-56 years (1
      woman and the rest men). Presenting signs and symptoms were thoracic murmurs,
      progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome.
      Pulmonary angiography showed that PPAS was predominantly located in main branches
      or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial
      narrowing was at the level of the segmental pulmonary arteries. Right heart
      catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to
      60 mmHg. Balloon dilation was performed in all patients, predominantly in the
      lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46%
      in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had
      follow-up echocardiograms at 1 year that showed stable echocardiographic
      findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic
      challenge. Therefore, a high index of suspicion during the initial evaluation of
      pulmonary hypertension is essential for its prompt diagnosis and adequate
      treatment. 

PMID- 25992284
TI  - Severe reversible pulmonary hypertension in smoldering multiple myeloma: two
      cases and review of the literature.
AB  - An association between pulmonary hypertension (PH) and POEMS syndrome
      (characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy, and skin changes) as well as other plasma cell dyscrasias, including
      multiple myeloma (MM), has been shown to exist. Recent case reports have
      identified a reversible form of PH that occurs outside of previously identified
      etiologies. We report two cases of PH in the setting of smoldering MM (SMM) that
      resolved with chemotherapy and stem cell transplantation. Although other features
      were individualized among the cases (dermatomyositis, scleromyxedema), treatment
      of MM and SMM resulted in a normalization of right ventricular systolic pressure
      and improvement in right ventricular dysfunction that was previously unresponsive
      to PH therapies. The magnitude and sustained nature of reversibility in these
      four cases could offer clues about the pathophysiology and treatment of PH. 

PMID- 25992285
TI  - Cancer-associated muscle weakness: What's bone got to do with it?
AB  - Cancer-associated muscle weakness is an important paraneoplastic syndrome for
      which there is currently no treatment. Tumor cells commonly metastasize to bone
      in advanced cancer to disrupt normal bone remodeling and result in morbidity that
      includes muscle weakness. Tumor in bone stimulates excessive osteoclast activity,
      which causes the release of growth factors stored in the mineralized bone matrix.
      These factors fuel a feed-forward vicious cycle of tumor growth in bone and bone
      destruction. Recent evidence indicates that these bone-derived growth factors can
      act systemically to cause muscle weakness. Muscle weakness can be caused by
      reduced muscle mass or reduced muscle function; in advanced disease, it is likely
      due to a combination of both reduced quantity and quality of muscle. In this
      review, we discuss possible mechanisms that lead to skeletal muscle weakness due
      to bone metastases. 

PMID- 25992286
TI  - Built environment and active play among Washington DC metropolitan children: A
      protocol for a cross-sectional study.
AB  - BACKGROUND: Research has demonstrated that children who participate in active
      play are more likely to be physically active, thereby improving long-term health
      outcomes. Many adult studies have also shown that neighborhood built environments
      can encourage or discourage routine physical activity. Limited evidence has
      demonstrated that children who reside in neighborhoods with a built environment
      that is more inviting to active play exhibit lower overweight and obesity rates
      as well as an overall better state of well-being. This Built Environment and
      Active Play (BEAP) Study aims to develop a neighborhood playability rating system
      in the Washington, DC (DMV) area. Similar to walkability scores, these
      playability scores will estimate how affable a neighborhood is to active play.
      The BEAP Study will attempt to provide a broad view of factors influencing the
      level and type of active play among children. METHODS/DESIGN: Using a cross
      sectional design, the BEAP Study will collect data using a mail questionnaire
      administered to the parents and/or guardians of 2000 children aged 7-12 years
      residing in select DMV areas in October of 2014. Questionnaire data, including
      information on active play, home and neighborhood characteristics, parental
      perceptions, and sociodemographic characteristics will be merged through a
      geographic information system (GIS) with objective built environment measures in
      the participants' neighborhoods. An ordered logit model will be used to regress
      an ordinal active play outcome on built environment exposure variables while
      adjusting for potential confounders. Upon the construction of the final model,
      predictor coefficients will be used as parameters in the scoring system to
      develop neighborhood playability scores. DISCUSSION: The BEAP Study intends to
      generate a neighborhood playability index by characterizing and quantifying
      children's active play using parent-reported physical activity data in children,
      GIS data and built environment measures in participant neighborhoods. The BEAP
      Study will improve our understanding of the built environment and childhood
      playability relationship while also contributing to the body of evidence-based
      built environment and physical activity research.

PMID- 25992287
TI  - Mothers Understand And Can do it (MUAC): a comparison of mothers and community
      health workers determining mid-upper arm circumference in 103 children aged from
      6 months to 5 years.
AB  - BACKGROUND: Mid-upper arm circumference (MUAC) was recently endorsed and
      recommended for screening for acute malnutrition in the community. The objective
      of this study was to determine whether a colour-banded MUAC strap would allow
      minimally trained mothers to screen their own children for malnutrition, without
      locating the mid-point of the left upper arm by measurement, as currently
      recommended. METHODS: A non-randomised non-blinded evaluation of mothers'
      performance when measuring MUAC after minimal training, compared with trained
      Community Health Workers (CHW) following current MUAC protocols. The study was
      conducted in 2 villages in Mirriah, Zinder region, Niger where mothers classified
      one of their children (n = 103) aged 6-59 months (the current age range for
      admission into community malnutrition programs) using the MUAC tape. RESULTS:
      Mothers' had a sensitivity and specificity for classification of their child's
      nutritional status of > 90% and > 80% respectively for global acute malnutrition
      (GAM, defined by a MUAC < 125 mm) and > 73% and > 98% for severe acute
      malnutrition (SAM, defined by a MUAC < 115 mm). The few children misclassified as
      not having SAM, were classified as having moderate acute malnutrition (MAM). The
      choice of arm did not influence the classification results; weighted Kappa of
      0.88 for mothers and 0.91 for CHW represent almost perfect agreement. Errors
      occurred at the class boundaries and no gross errors were made. CONCLUSIONS:
      Advanced SAM is associated with severe complications, which often require
      hospital admission or cause death. Mothers (with MUAC tapes costing $0.06) can
      screen their children frequently allowing early diagnosis and treatment thereby
      becoming the focal point in scaling-up community management of acute
      malnutrition. TRIAL REGISTRATION: The trial is registered with clinicaltrials.gov
      (Trial number NCT01790815).

PMID- 25992288
TI  - Preservation of tumor-host immune interactions with luciferase-tagged imaging in
      a murine model of ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is immunogenic and residual tumor volume after surgery
      is known to be prognostic. Ovarian cancer often follows a recurring-remitting
      course and microscopic disease states may present ideal opportunities for immune
      therapies. We sought to establish the immune profile of a murine model of ovarian
      cancer that allows in vivo tumor imaging and the quantitation of microscopic
      disease. RESULTS AND DISCUSSION: Baseline imaging and weight measurements were
      taken within 1 and 2 weeks after intraperitoneal tumor injection, respectively.
      Significantly higher photons per second from baseline imaging were first observed
      5 weeks after tumor cell injection (p < 0.05) and continued to be significant
      through 8 weeks after injection (p < 0.01), whereas a significant increase in
      weight above baseline was not observed until day 56 (p < 0.0001). Expression of
      luc2 in ID8 cells did not alter the cellular immune microenvironment of the
      tumor. FOXP3+ T cells were more likely to be detected in the intraepithelial
      compartment and CD4+ T cells in the stroma as compared to CD3+ T cells, which
      were found equally in stroma and intraepithelial compartments. CONCLUSIONS: Use
      of an intraperitoneal tumor expressing a codon-optimized firefly luciferase in an
      immunocompetent mouse model allows tumor quantitation in vivo and detection of
      microscopic tumor burdens. Expression of this foreign protein does not
      significantly effect tumor engraftment or the immune microenvironment of the ID8
      cells in vivo and may allow novel immunotherapies to be assessed in a murine
      model for their translational potential to ovarian cancers in remission or
      minimal disease after primary cytoreductive surgery or chemotherapy. METHODS:
      Mouse ovarian surface epithelial cells from C57BL6 mice transformed after serial
      passage in vitro were transduced with a lentiviral vector expressing a codon
      optimized firefly luciferase (luc2). Cell lines were selected and luc2 expression
      functionally confirmed in vitro. Cell lines were intraperitoneally (IP) implanted
      in albino C57BL/6/BrdCrHsd-Tyrc mice and albino B6(Cg)-Tyrc-2 J/J mice for serial
      imaging. D-luciferin substrate was injected IP and tumors were serially imaged in
      vivo using a Xenogen IVIS. Tumor take, weights, and luminescent intensities were
      measured. Immunohistochemistry was performed on tumors and assessed for immune
      infiltrates in stromal and intraepithelial compartments.

PMID- 25992290
TI  - Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab
      immunotherapy in the setting of active ulcerative colitis.
AB  - While blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) T cell regulatory
      receptor has become a commonly utilized strategy in the management of advanced
      melanoma, many questions remain regarding the use of this agent in patient
      populations with autoimmune disease. We present a case involving the treatment of
      a patient with stage IV melanoma and ulcerative colitis (UC) with anti-CTLA-4
      antibody immunotherapy. Upon initial treatment, the patient developed grade III
      colitis requiring tumor necrosis factor-alpha (TNF-alpha) blocking antibody
      therapy, however re-treatment with anti-CTLA-4 antibody following a total
      colectomy resulted in a rapid complete response accompanied by the development of
      a tracheobronchitis, a previously described extra-intestinal manifestation of UC.
      This case contributes to the evolving literature on the use of checkpoint
      inhibitors in patients also suffering from autoimmune disease, supports future
      clinical trials investigating the use of these agents in patients with autoimmune
      diseases, and suggests that an understanding of the specific molecular pathways
      involved in a patient's autoimmune pathology may provide insight into the
      development of more effective novel combinatorial immunotherapeutic strategies. 

PMID- 25992289
TI  - NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma
      treated with interleukin-2 (IL-2) and CTLA-4 blockade.
AB  - BACKGROUND: Melanoma is one of the few types of cancer with an increasing annual
      incidence. While a number of immunotherapies for melanoma have been associated
      with significant clinical benefit, including high-dose IL-2 and cytotoxic T
      lymphocyte antigen 4 (CTLA-4) blockade, clinical response to either of these
      single agents has been limited to 11-20% of treated patients. Therefore, in this
      study, we sought to test the hypothesis that the combination of IL-2 and CTLA-4
      blockade could mediate a more profound therapeutic response. METHODS: Here, B6
      mice were challenged with poorly immunogenic B16 melanoma on day 0, and treated
      with CTLA-4 blocking antibody (100 MUg/mouse) on days 3, 6, and 9, and IL-2
      (100,000 units) twice daily on days 4-8, or both. RESULTS: A highly significant
      synergistic effect that delayed tumor growth and prolonged survival was
      demonstrated with the combination immunotherapy compared to either monotherapy
      alone. The therapeutic effect of combination immunotherapy was dependent on both
      CD8+ T and NK cells and co-depletion of these subsets (but not either one alone)
      abrogated the therapeutic effect. CTLA-4 blockade increased immune cell
      infiltration (including CD8+ T cells and NK cells) in the tumor and IL-2 reduced
      the proportion of highly differentiated/exhausted tumor-infiltrating NK cells.
      CONCLUSIONS: These results have implications for the design of clinical trials in
      patients with metastatic melanoma and provide new insights into how the immune
      system may be mediating anti-tumor activity with combination IL-2 and CTLA-4
      blockade in melanoma.

PMID- 25992291
TI  - Survivin-specific CD4+ T cells are decreased in patients with survivin-positive
      myeloma.
AB  - BACKGROUND: Survivin is a small protein inhibitor of apoptosis and a tumor
      associated antigen. Survivin expression in multiple myeloma is associated with
      poor prognosis, disease progression, and drug resistance. The CD4+ response
      against survivin remains uncharacterized. METHODS: In order to better understand
      the anti-tumor immune response to survivin, and optimize vaccination strategies,
      we characterized the spontaneous CD4+CD25- T cell response against survivin in
      healthy donors and myeloma patients using survivin derived peptide pools.
      RESULTS: Healthy donors and myeloma patients' CD4+CD25- T cells exhibited a
      proliferative and IFN-gamma response against survivin peptides loaded onto
      autologous dendritic cells. We employed limiting dilution analysis to quantify
      the precursor frequency of survivin reactive CD4+CD25- T cells. Multiple myeloma
      patients (range 0% to 2.2x10(-3)%, n=12) had fewer survivin reactive CD4+CD25- T
      cells than healthy blood donors (range 1.1x10(-3) to 8.4x10(-3)%, n=10), p =
      0.021. The survivin reactive CD4+CD25- T cell precursor frequency was inversely
      associated with tumor survivin mRNA expression (p = 0.0028, r = -1.0, n = 6), and
      survivin tumor protein expression by IHC (p = 0.0295, r = -0.67, n = 10). A full
      length mutant survivin protein-pulsed dendritic cell vaccine expanded survivin
      reactive CD4+CD25- T cells after 12 days of in vitro culture (range 0-540x,median
      = 42x), and expansion was achieved even in patients with low baseline survivin
      reactive CD4+ precursors. CONCLUSIONS: We have, for the first time, quantified
      the circulating CD4+CD25- precursor frequency against survivin and demonstrated
      this is lower in myeloma patients than healthy donors. The number of survivin
      reactive CD4+CD25- T cells is inversely associated with tumor survivin expression
      suggesting suppression of survivin responsive CD4+CD25- T cells. Further
      exploration of a full length mutant survivin protein vaccine which expands
      survivin reactive CD4+ cells independent of the survivin reactive precursor
      frequency is warranted.

PMID- 25992292
TI  - Combination immunotherapy with alpha-CTLA-4 and alpha-PD-L1 antibody blockade
      prevents immune escape and leads to complete control of metastatic osteosarcoma.
AB  - BACKGROUND: Osteosarcoma is one of the most common bone cancers in children. Most
      patients with metastatic osteosarcoma die of pulmonary disease and limited
      curative therapeutic options exist for such patients. We have previously shown
      that PD-1 limits the efficacy of CTL to mediate immune control of metastatic
      osteosarcoma in the K7M2 mouse model of pulmonary metastatic disease and that
      blockade of PD-1/PD-L1 interactions can partially improve survival outcomes by
      enhancing the function of osteosarcoma-specific CTL. However, PD-1/PD-L1 blockade
      treated mice eventually succumb to disease due to selection of PD-L1 mAb
      resistant tumor cells. We investigated the mechanism of tumor cell resistance
      after blockade, and additional combinational therapies to combat resistance.
      METHODS: We used an implantable model of metastatic osteosarcoma, and evaluated
      survival using a Log-rank test. Cellular analysis of the tumor was done post
      mortem with flow cytometry staining, and evaluated using a T-test to compare
      treatment groups. RESULTS: We show here that T cells infiltrating PD-L1 antibody
      resistant tumors upregulate additional inhibitory receptors, notably CTLA-4,
      which impair their ability to mediate tumor rejection. Based on these results we
      have tested combination immunotherapy with alpha-CTLA-4 and alpha-PD-L1 antibody
      blockade in the K7M2 mouse model of metastatic osteosarcoma and show that this
      results in complete control of tumors in a majority of mice as well as immunity
      to further tumor inoculation. CONCLUSIONS: Thus, combinational immunotherapy
      approaches to block additional inhibitory pathways in patients with metastatic
      osteosarcoma may provide new strategies to enhance tumor clearance and resistance
      to disease.

PMID- 25992293
TI  - Pharmacokinetics and the optimal regimen for levofloxacin in critically ill
      patients receiving continuous hemodiafiltration.
AB  - The aim of this study was to establish the pharmacokinetics of levofloxacin
      (LVFX) and determine the optimal dose of this drug in critically ill patients
      receiving continuous hemodiafiltration (CHDF). The results of in vivo and in
      vitro studies showed the pharmacokinetics of LVFX total clearance (CLtotal)
      according to the creatinine clearance (CLCre), dialysate flow (QD), and
      ultrafiltrate flow (QF), to be as follows: CLtotal (l/h) = 0.0836 * CLCre
      (ml/min) + 0.013 * body weight (kg) + 0.94(QD + QF) (l/h). The optimal dose of
      LVFX was expressed by the following formula: 50 * CLtotal. These results
      demonstrate that the usual dose of LVFX (500 mg) was sufficient for the patients
      evaluated in this study. 

PMID- 25992294
TI  - Assessment of left ventricle preload by transthoracic echocardiography: an easy
      task?
AB  - In sicker hearts, right atrial pressure (an estimation of right ventricle
      preload) are not equivalent to left atrial pressure (an estimation of left
      ventricle preload). Both right and left atrial pressures are frequently estimated
      using invasive techniques and also transthoracic echocardiography. While right
      atrial pressure is easy to obtain with transthoracic echocardiography, the
      assessment of left ventricle preload or filling pressures is not simple. In
      relation to the study of Sasai et al. (J Intensive Care 2(1):58, 2014), this
      paper discusses in a succinct manner how to think and assess the left ventricle
      preload by transthoracic echocardiography. 

PMID- 25992295
TI  - Trends in the utilization of antihypertensive medications among Palestine
      refugees in Jordan, 2008-2012.
AB  - OBJECTIVES: The purpose of this study is to describe trends in the utilization of
      antihypertensive medications, overall and by type of medication, specifically
      thiazide diuretics, as well as uncontrolled hypertension, in the Palestine
      refugee population in Jordan between 2008 and 2012. METHODS: We analyzed
      aggregate procurement data on antihypertensive medications derived from the
      United Nations Relief and Works Agency (UNRWA) pharmacy records between 2008 and
      2012. Antihypertensive medications were aggregated and utilization was calculated
      overall and for specific types of antihypertensive medications (e.g. beta
      blockers, diuretics). We used the WHO (World Health Organization) defined daily
      dose (DDD) methodology, often used to evaluate drug utilization patterns using
      aggregate data, to calculate utilization defined as DDDs per 100 persons with
      hypertension. In addition, UNRWA medical records were used to measure the
      prevalence of uncontrolled hypertension in the primary care setting. Uncontrolled
      hypertension was defined as a systolic/diastolic blood pressure >=140/90 in at
      least 2 out of 3 readings, one of which is the most recent reading, during the
      year for a patient diagnosed with hypertension. RESULTS: Overall, total
      utilization of antihypertensive medications has not changed between 2008 and
      2012; hypertensive patients persistently used at least 2 antihypertensive
      medications daily (range 200-280 DDDs/100 patients with hypertension) during this
      five-year period. However, there is significant variation in utilization patterns
      by type of antihypertensive medication. While Angiotensin Converting Enzyme
      Inhibitors (ACE-I) were persistently the most commonly used antihypertensive
      medication, there utilization significantly (P < 0.05) declined by 26%. However,
      there was a statistically significant increase of 124% in the utilization of
      thiazide diuretics. Further, the prevalence of uncontrolled hypertension has also
      declined at a rate of 3% annually between 2008 and 2012. CONCLUSION: Our findings
      indicate that the STGs for hypertension management implemented in 2009 as part of
      UNRWA's essential drug program have increased the utilization of thiazide
      diuretics, and potentially contributed to improvements in hypertension control.
      This study also demonstrates that feasibility of drug utilization studies in
      monitoring and evaluating trends in the use of essential medications in low
      resource settings.

PMID- 25992296
TI  - Preparation of hydrophilic nanofiltration membranes for removal of
      pharmaceuticals from water.
AB  - Asymmetric polyethersulfone (PES) nanofiltration membranes were prepared via
      phase inversion technique. PES polymer, Brij 58 as surfactant additive,
      polyvinylpyrrolidone (PVP) as pore former and 1-methyl-2-pyrrolidone (NMP) as
      solvent were used in preparation of the casting solutions. Distillated water was
      used as the gelation media. The scanning electron microscopy (SEM) images and
      measurements of contact angle (CA) and zeta potential were used to characterize
      the prepared membranes. Also performance of the membranes was examined by
      determining the pure water flux (PWF) and pharmaceuticals rejection. The addition
      of Brij 58 to the casting solution resulted in formation of the membranes with
      higher thickness and more porous structure in the sublayer in comparison with the
      net PES membrane. The surface hydrophilicity of the membranes was remarkably
      enhanced via the presence of Brij 58 in the casting solution, so that, the
      contact angel diminished from 74.7 degrees  to 28.3 degrees  with adding 6 wt. %
      of Brij 58 to the casting solution. The addition of Brij 58 to the casting
      solution resulted in formation of the membranes with superior PWF and higher
      rejection of amoxicillin and ceftriaxone in comparison with the pure PES
      membrane. 

PMID- 25992297
TI  - Soil to plant transfer of alpha activity in potato plants: impact of phosphate
      fertilizers.
AB  - BACKGROUND: Radionuclides in the phosphate fertilizers belonging to (232)Th and
      (238)U and (40) K are the major contributors to the outdoor terrestrial natural
      radiation. These radionuclides are transferred from fertilizer to food through
      soil. MATERIALS AND METHODS: Present work deals with the alpha activity in the
      different parts of the potato (Solanum Tuberosum) plants grown under controlled
      pots experiment using different amounts of phosphate fertilizers and urea. Alpha
      activities have been measured by track etch technique using the solid-state
      nuclear track detectors (LR-115). RESULTS: Translocation factor for the fruit
      (edible Part) varied from 0.13 (for DAP) to 0.73 (for PF) with an average of 0.40
      +/- 0.26 for the plant grown with 20 g of fertilizers. Translocation factors
      increased with the increase in amount of fertilizers having value 0.51 +/- 0.31
      for the plant grown with 50 g of fertilizers. The translocation factor for the
      lower and the upper part of leaves varied from 0.44 to 0.67 and 0.22 to 0.83 with
      an average value 0.55 +/- 0.15 and 0.45 +/- 0.23 respectively. The transfer
      factor (TF's) for the potato plants varied from 1.5 * 10(-2) to 1.03 * 10(-1) for
      root, from 1.3 * 10(-2) to 1.23 * 10(-1) for stem, from 2.1 * 10(-3) to 4.5 * 10(
      2) for fruit and from 5.4 * 10(-3) to 5.8 * 10(-3) for lower part of the leaves
      after 105 days of the plantation. CONCLUSIONS: The results revealed that the
      alpha activity in the potato plants was higher in case of the plants grown with
      the use of phosphate fertilizers than with other fertilizers.

PMID- 25992298
TI  - The impact of occupational experience on cognitive and physical functional status
      among older adults in a representative sample of Korean subjects.
AB  - OBJECTIVE: This study investigated the impact of occupation on cognitive and
      physical function within an occupational window of the past 15 years using a
      nationally representative sample in Korea. METHODS: A total of 4,408 subjects
      aged 60 and older were selected from the Korean Longitudinal Study of Aging
      (KLoSA). Functional health was evaluated using the Korean versions of the Mental
      State Examination (K-MMSE), Instrumental Activities of Daily Living (K-IADL), and
      Activities of Daily Living (K-ADL) measures. RESULTS: The prevalence of lower
      function was higher among women than among men, and employed persons had better
      cognitive and physical function compared with the retired and unemployed. Longer
      work duration during the past 15 years significantly and positively affected all
      measures of function in men, whereas it only improved physical function in women.
      Manual laborers exhibited improved functional capacity with longer work durations
      over the past 15 years, although they presented lower functional scores compared
      with non-manual laborers. There was a curvilinear relationship of work duration
      with cognitive and physical function among men and manual laborers. CONCLUSION:
      In our population, longer work duration, especially for men and for manual
      laborers, appears to be a significant contributor to the cognitive and physical
      function of older people.

PMID- 25992299
TI  - The effect of applying ethnicity-specific spirometric reference equations to
      Asian migrant workers in Korea.
AB  - OBJECTIVES: Asian migrant workers in Korea have various ethnicities. The purpose
      of this study was to evaluate the difference in spirometric interpretation made
      using the set of third National Health and Nutrition Examination Survey (NHANES
      III) reference equations and the relevant ethnicity-specific reference sets.
      METHODS: Spirometry was performed on 166 migrant and 498 Korean male workers
      between March and November 2012. We analyzed the spirometric data of healthy
      never-smokers. Spirometric patterns were evaluated using the NHANES III reference
      set and some relevant ethnicity-specific equations (Eom's equation for Koreans,
      Ip's equation for East Asians, Crapo's equation for Central Asians, Memon's
      equation for South Asians, and Gnanou's equation for Southeast Asian people).
      RESULTS: In all migrant groups except the Central Asian group, the forced
      expiratory volume in 1 second percentage (FEV1%) and forced vital capacity
      percentage (FVC%) calculated using each of the ethnicity-specific reference
      equations considered were significantly higher than those calculated using the
      NHANES III reference set. This study showed that in the evaluation of the
      spirometric result of subjects from Southeast Asia or South Asia, the percentage
      of cases with an abnormal FEV1 or FVC increased when the NHANES III set of
      equations was used as compared to when the ethnicity-specific equations were
      used. CONCLUSIONS: We found that the spirometric results of all ethnic groups
      were higher and the composition of the abnormal spirometric result was lower when
      the ethnicity-specific reference equations were used instead of the NHANES III
      reference set.

PMID- 25992300
TI  - Concurrent biliary drainage and portal vein embolization in preparation for
      extended hepatectomy in patients with biliary cancer.
AB  - BACKGROUND: Patients with perihilar cholangiocarcinoma and gallbladder cancer
      extending into the hilum often present with jaundice and a small future liver
      remnant (FLR). If resectable, preoperative biliary drainage and portal vein
      embolization (PVE) are indicated. Classically, these measures have been performed
      sequentially, separated by 4-6 weeks. PURPOSE: To report on a new regime where
      percutaneous transhepatic biliary drainage (PTBD) and PVE are performed
      simultaneously, shortening the preoperative process. MATERIAL AND METHODS: Six
      patients were treated with concurrent PTBD and PVE under general anesthesia.
      RESULTS: Surgical exploration followed the combined procedure after 35 days
      (range, 28-51 days). The FLR ratio increased from 22% to 32%. Three patients
      developed cholangitis after the procedure. CONCLUSION: The combined approach of
      PTBD and PVE seems feasible, but more studies on morbidity are warranted.

PMID- 25992301
TI  - Cortical desmoids in adolescent top-level athletes.
AB  - Two adolescent, highly active athletes are presented with unspecific symptoms of
      anterior knee pain. Conventional radiographs and magnetic resonance imaging (MRI)
      showed a suspicious but pathognomonic cortical irregularity of the dorsal, medial
      femoral condyle. Cortical desmoid is one of the most common incidental osseous
      findings on conventional radiographs and MRI of the knee. It often needs no
      follow-up examination in asymptomatic patients. Malignancy needs however to be
      ruled out. 

PMID- 25992302
TI  - Sepsis outcomes in patients receiving statins prior to hospitalization for
      sepsis: comparison of in-hospital mortality rates between patients who received
      atorvastatin and those who received simvastatin.
AB  - BACKGROUND: The purpose of this study is to compare the in-hospital mortality
      rates between septic patients receiving statins and those that did not prior to
      developing sepsis. We compared subgroups receiving atorvastatin and simvastatin
      because these two drugs differ in their pharmacologic properties. METHODS: This
      study was a retrospective analysis of patients selected from an institutional
      data base of patients hospitalized with sepsis. The study patients were drawn
      from a data base of 1,961 hospitalized patients with sepsis and included patients
      who met selection criteria and who were studied for HMG-CoA reductase inhibitor
      (statin) use both prior to and during hospitalization. The in-hospital mortality
      rates of patients receiving statins and those that did not prior to developing
      sepsis were compared. In-hospital mortality rates of patient subgroups receiving
      atorvastatin and simvastatin were also compared. A multivariable analysis was
      conducted with in-hospital mortality as the outcome variable and with multiple
      risk factors to include atorvastatin and simvastatin use. RESULTS: The mortality
      rate for 359 patients receiving statins prior to hospitalization for sepsis was
      not significantly different than that for 1,302 patients who did not receive pre
      hospital statins (26.5% versus 30.4%, p > 0.05). The mortality rate for 92
      patients who had received atorvastatin prior to hospitalization was significantly
      less than that of 253 patients who received simvastatin (18.5% versus 30.0%, p =
      0.032). The use of atorvastatin prior to sepsis was independently associated with
      lower in-hospital mortality in a multivariable analysis of sepsis risk factors (p
      = 0.021, OR = 0.455). Patients who received atorvastatin prior to hospitalization
      for sepsis and had statins continued in hospital had a very low mortality rate
      that was significantly less than that of those patients who never received
      statins (15.7% versus 30.8%, p = 0.007). CONCLUSIONS: Pre-hospital atorvastatin
      use was associated with improved in-hospital mortality in septic patients when
      compared with pre-hospital simvastatin use and was independently associated with
      an improved outcome when compared to other sepsis risk factors. The effect of
      statins in patients with sepsis may be different for individual statins.

PMID- 25992303
TI  - 2014 ebola outbreak: media events track changes in observed reproductive number.
AB  - In this commentary, we consider the relationship between early outbreak changes
      in the observed reproductive number of Ebola in West Africa and various media
      reported interventions and aggravating events. We find that media reports of
      interventions that provided education, minimized contact, or strengthened
      healthcare were typically followed by sustained transmission reductions in both
      Sierra Leone and Liberia. Meanwhile, media reports of aggravating events
      generally preceded temporary transmission increases in both countries. Given
      these preliminary findings, we conclude that media reported events could
      potentially be incorporated into future epidemic modeling efforts to improve mid
      outbreak case projections. 

PMID- 25992304
TI  - Functional screening system for yeast-secreted peptides acting on G-protein
      coupled receptors.
AB  - We established a novel functional screening system for peptides acting on G
      protein coupled receptors (GPCRs). Peptides are a promising drug scaffold because
      of their intermediate molecular size between that of therapeutic small molecules
      and antibodies. They also offer potential advantages of targeting not only
      membrane proteins but also intracellular protein-protein interactions. Phage
      display technology has been used for exploring novel peptides acting on GPCRs,
      but it is unclear whether the identified peptides functionally modulate targets
      because the technology selects peptides based on binding ability but not
      functional activity to targets. In a novel screening system that we established,
      yeast cells were utilized as a peptide producer while mammalian cells stably
      producing the receptor for glucagon-like peptide 1 (GLP1R) were used as a
      biosensor for receptor activation. Three kinds of GLP1R agonists secreted by
      yeasts were successfully detected for their functional activities without any
      purification and condensation of those peptides. By applying the functional
      screening system, we were able to identify GLP1R agonist-secreting yeasts based
      on GLP1R activation from the cell mixture containing a number of background
      yeasts that produced non-active control peptides. Further applications of this
      system would include not only activity evaluation of bioactive peptides without
      chemical synthesis but also discovery of novel peptides activating druggable
      GPCRs. 

PMID- 25992305
TI  - Addressing preference heterogeneity in public health policy by combining Cluster
      Analysis and Multi-Criteria Decision Analysis: Proof of Method.
AB  - The use of subgroups based on biological-clinical and socio-demographic variables
      to deal with population heterogeneity is well-established in public policy. The
      use of subgroups based on preferences is rare, except when religion based, and
      controversial. If it were decided to treat subgroup preferences as valid
      determinants of public policy, a transparent analytical procedure is needed. In
      this proof of method study we show how public preferences could be incorporated
      into policy decisions in a way that respects both the multi-criterial nature of
      those decisions, and the heterogeneity of the population in relation to the
      importance assigned to relevant criteria. It involves combining Cluster Analysis
      (CA), to generate the subgroup sets of preferences, with Multi-Criteria Decision
      Analysis (MCDA), to provide the policy framework into which the clustered
      preferences are entered. We employ three techniques of CA to demonstrate that not
      only do different techniques produce different clusters, but that choosing among
      techniques (as well as developing the MCDA structure) is an important task to be
      undertaken in implementing the approach outlined in any specific policy context.
      Data for the illustrative, not substantive, application are from a Randomized
      Controlled Trial of online decision aids for Australian men aged 40-69 years
      considering Prostate-specific Antigen testing for prostate cancer. We show that
      such analyses can provide policy-makers with insights into the criterion-specific
      needs of different subgroups. Implementing CA and MCDA in combination to assist
      in the development of policies on important health and community issues such as
      drug coverage, reimbursement, and screening programs, poses major challenges 
      conceptual, methodological, ethical-political, and practical - but most are
      exposed by the techniques, not created by them. 

PMID- 25992306
TI  - The association of tumor-to-background ratios and SUVmax deviations related to
      point spread function and time-of-flight F18-FDG-PET/CT reconstruction in
      colorectal liver metastases.
AB  - BACKGROUND: The maximum standardized uptake value (SUVmax) is a common clinical
      parameter for quantification in F18-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG-PET/CT), but it is influenced by image
      reconstruction. The aim of this study was to analyze the association of SUVmax
      deviations related to point spread function (PSF) and time-of-flight (TOF)
      reconstruction with tumor-to-background ratios (TBR) in colorectal liver
      metastases (CRLM). METHODS: Fifteen patients (f, 6; m, 9; median age, 59 years;
      range, 32 to 72 years) with 28 liver metastases were included retrospectively.
      FDG-PET/CT imaging (median activity, 237 MBq; range, 231 to 252 MBq; median
      uptake, 61 min; range, 55 to 67 min) was performed on a Siemens Biograph mCT 64
      followed by image reconstruction using 3D-ordered subset expectation maximization
      (3D-OSEM) or 3D-OSEM with PSF modeling - both with and without TOF information.
      Differences in SUVmax were analyzed using the Friedman test and Wilcoxon test for
      paired non-parametric data. The correlation of inter-method differences with the
      lesions' TBR was studied using Spearman's rank correlation coefficient (rho).
      Differences between lesions with low (<4.8) and high (>4.8) TBR were analyzed
      using the Mann-Whitney U test (TBR measured with 3D-OSEM; binarized by its
      median). RESULTS: There was a significant correlation of the lesions' TBR with
      relative SUVmax differences related to PSF (PSF + TOF vs. 3D-OSEM + TOF, rho =
      0.61; PSF vs. 3D-OSEM, rho = 0.52) or TOF (PSF + TOF vs. PSF, rho = -0.58; 3D
      OSEM + TOF vs. 3D-OSEM, rho = -0.61). Accordingly, PSF algorithms only showed
      higher SUVmax than non-PSF algorithms in lesions with a high TBR (median
      differences at low/high TBR, +2.6%/+9.1% [PSF + TOF vs. 3D-OSEM + TOF];
      +0.7%/+6.4% [PSF vs. 3D-OSEM]). TOF integration also led to higher SUVmax but
      mainly at low TBR (low/high TBR, +10.4%/+1.8% [PSF + TOF vs. PSF]; +8.6%/-0.1%
      [3D-OSEM + TOF vs. 3D-OSEM]). CONCLUSIONS: Both PSF and TOF reconstruction
      resulted in a substantial alteration of SUVmax in CRLM. TOF provided the highest
      SUVmax increase in low-contrast lesions while - vice versa - PSF showed the most
      relevant increase in high-contrast lesions. Thus, one should be aware that
      quantitative analyses of lesions with varying TBR, e.g., in radiotherapy or
      follow-up studies, may be mainly affected by either PSF or TOF reconstruction,
      respectively.

PMID- 25992308
TI  - Early diagnosis and treatment of breast cancer in Japanese kidney transplant
      recipients: a single center experience.
AB  - BACKGROUND: The incidence of malignancies in kidney transplant recipients is
      increasing. Breast cancer is a common malignancy after kidney transplantation and
      can be more aggressive in kidney transplant recipients than in the general
      population. In this study, we evaluated the incidence and prognosis of breast
      cancer in kidney transplant recipients. FINDINGS: Between 1993 and 2013, 750
      kidney transplant patients were followed-up at our center. Since 1999, annual
      physical examination, mammography, and breast ultrasonography have been performed
      for such patients. Diagnostic studies, including core needle or mammotome biopsy,
      were performed for suspected malignancies. Patients with malignant neoplasm were
      administered the appropriate treatment and followed-up to assess tumor response
      and symptoms. Nine patients were diagnosed with breast cancer during the follow
      up period. The mean age at the initial detection of the breast cancer was 47.7 +/
      8.4 years. The mean interval from transplantation to diagnosis was 148.7 +/-
      37.1 months. Of the 9 patients, 8 were detected through the screening test; 7
      were treated with breast conservative surgery and 1 was treated with modified
      radical mastectomy. The cancer stages were 0 (n = 2), I (n = 6), and II (n = 1).
      The incidence of breast cancer tended to be unchanged with time between
      transplantation and diagnosis, inconsistent with the increase in the duration of
      immunosuppression. CONCLUSION: Annual screening tests are crucial in the early
      diagnosis of breast cancer. Early treatment of breast cancer can result in an
      excellent prognosis in kidney transplant recipients.

PMID- 25992307
TI  - Shamba Maisha: Pilot agricultural intervention for food security and HIV health
      outcomes in Kenya: design, methods, baseline results and process evaluation of a
      cluster-randomized controlled trial.
AB  - BACKGROUND: Despite advances in treatment of people living with HIV, morbidity
      and mortality remains unacceptably high in sub-Saharan Africa, largely due to
      parallel epidemics of poverty and food insecurity. METHODS/DESIGN: We conducted a
      pilot cluster randomized controlled trial (RCT) of a multisectoral agricultural
      and microfinance intervention (entitled Shamba Maisha) designed to improve food
      security, household wealth, HIV clinical outcomes and women's empowerment. The
      intervention was carried out at two HIV clinics in Kenya, one randomized to the
      intervention arm and one to the control arm. HIV-infected patients >18 years, on
      antiretroviral therapy, with moderate/severe food insecurity and/or body mass
      index (BMI) <18.5, and access to land and surface water were eligible for
      enrollment. The intervention included: 1) a microfinance loan (~$150) to purchase
      the farming commodities, 2) a micro-irrigation pump, seeds, and fertilizer, and
      3) trainings in sustainable agricultural practices and financial literacy.
      Enrollment of 140 participants took four months, and the screening-to-enrollment
      ratio was similar between arms. We followed participants for 12 months and
      conducted structured questionnaires. We also conducted a process evaluation with
      participants and stakeholders 3-5 months after study start and at study end.
      DISCUSSION: Baseline results revealed that participants at the two sites were
      similar in age, gender and marital status. A greater proportion of participants
      at the intervention site had a low BMI in comparison to participants at the
      control site (18% vs. 7%, p = 0.054). While median CD4 count was similar between
      arms, a greater proportion of participants enrolled at the intervention arm had a
      detectable HIV viral load compared with control participants (49% vs. 28%,
      respectively, p < 0.010). Process evaluation findings suggested that Shamba
      Maisha had high acceptability in recruitment, delivered strong agricultural and
      financial training, and led to labor saving due to use of the water pump.
      Implementation challenges included participant concerns about repaying loans,
      agricultural challenges due to weather patterns, and a challenging partnership
      with the microfinance institution. We expect the results from this pilot study to
      provide useful data on the impacts of livelihood interventions and will help in
      the design of a definitive cluster RCT. TRIAL REGISTRATION: This trial is
      registered at ClinicalTrials.gov, NCT01548599.

PMID- 25992309
TI  - Functional and expression analyses of two kinds of betaine aldehyde
      dehydrogenases in a glycinebetaine-hyperaccumulating graminaceous halophyte,
      Leymus chinensis.
AB  - Glycinebetaine (GB) is an important compatible solute for salinity tolerance in
      many plants. In this study, we analyzed the enzymatic activity and the expression
      level of betaine aldehyde dehydrogenase (BADH), an important enzyme that
      catalyzes the last step in the GB synthesis in Leymus chinensis, a GB
      hyperaccumulating graminaceous halophyte, and compared with those of barley, a
      graminaceous glycophyte. We have isolated cDNAs for two BADH genes, LcBADH1 and
      LcBADH2. LcBADH1 has a putative peroxisomal signal peptide (PTS1) at its C
      terminus, while LcBADH2 does not have any typical signal peptide. Using
      immunofluorescent labeling, we showed that BADH proteins were localized to the
      cytosol and dot-shaped organelles in the mesophyll and bundle sheath cells of
      L.chinensis leaves. The affinity of recombinant LcBADH2 for betaine aldehyde was
      comparable to other plant BADHs, whereas recombinant LcBADH1 showed extremely low
      affinity for betaine aldehyde, indicating that LcBADH2 plays a major role in GB
      synthesis in L. chinensis. In addition, the recombinant LcBADH2 protein was
      tolerant to NaCl whereas LcBADH1 wasn't. The kinetics, subcellular and tissue
      localization of BADH proteins were comparable between L. chinensis and barley.
      The activity and expression level of BADH proteins were higher in L. chinensis
      compared with barley under both normal and salinized conditions, which may be
      related to the significant difference in the amount of GB accumulation between
      two plants. 

PMID- 25992310
TI  - A nationwide postal survey on the perception of Malaysian public healthcare
      providers on family medicine specialists' (PERMFAMS) clinical performance,
      professional attitudes and research visibility.
AB  - Perception of healthcare providers who worked with family medicine specialists
      (FMSs) could translate into the effectiveness of primary healthcare delivery in
      daily practices. This study examined perceptions of public healthcare
      providers/professionals (PHCPs) on FMSs at public health clinics throughout
      Malaysia. This was a cross-sectional study in 2012-2013 using postal method
      targeting PHCPs from three categories of health facilities, namely health
      clinics, health offices and hospitals. A structured questionnaire was developed
      to assess PHCP's perception of FMS's clinical competency, safety practice,
      ethical and professional values, and research involvement. It consists of 37
      items with Likert scale of strongly disagree (a score of 1) to strongly agree (a
      score of 5). Interaction and independent effect of the independent variables were
      tested and adjusted means score were reported. The participants' response rate
      was 58.0% (780/1345) with almost equal proportion from each of the three public
      healthcare facilities. There were more positive perceptions than negative among
      the PHCPs. FMSs were perceived to provide effective and safe treatment to their
      patients equally disregards of patient's social background. However, there were
      some concerns of FMSs not doing home visits, not seeing walk-in patients, had
      long appointment time, not active in scientific research, writing and
      publication. There were significant differences in perception based on a
      respondent's health care facility (p < 0.0001) and frequency of encounter (p <
      0.0001). PHCPs had overall positive perceptions on FMSs across all the domains
      investigated. PHCPs from different health care facilities and frequency of
      encounter with FMSs had different perception. Practicing FMSs could improve on
      the critical service areas that were perceived to be important but lacking. FMSs
      might need further support in conducting research and writing for publication. 

PMID- 25992311
TI  - Genetic variants and risk of gastric cancer: a pathway analysis of a genome-wide
      association study.
AB  - This study aimed to discover candidate single nucleotide polymorphisms (SNPs) for
      hypothesizing significant biological pathways of gastric cancer (GC). We
      performed an Identify Candidate Causal SNPs and Pathways (ICSNPathway) analysis
      using a GC genome-wide association study (GWAS) dataset, including 472,342 SNPs
      in 2,240 GC cases and 3,302 controls of Asian ethnicity. By integrating linkage
      disequilibrium analysis, functional SNP annotation, and pathway-based analysis,
      seven candidate SNPs, four genes and 12 pathways were selected. The ICSNPathway
      analysis produced 4 hypothetical mechanisms of GC: (1) rs4745 and rs12904 ->
      EFNA1 -> ephrin receptor binding; (2) rs1801019 -> UMPS -> drug and pyrimidine
      metabolism; (3) rs364897 -> GBA -> cyanoamino acid metabolism; and (4)
      rs11187870, rs2274223, and rs3765524 -> PLCE1 -> lipid biosynthetic process,
      regulation of cell growth, and cation homeostasis. This pathway analysis using
      GWAS dataset suggests that the 4 hypothetical biological mechanisms might
      contribute to GC susceptibility. 

PMID- 25992312
TI  - Predictors of life satisfaction among Asian American adolescents- analysis of add
      health data.
AB  - Life satisfaction correlates with adolescent risk taking behavior and their
      outcomes in adulthood. Despite the fast rise in numbers of Asian adolescents in
      the U.S., the predictors of their life satisfaction are not well understood. This
      study examined the relationship between several demographic and contextual
      factors and global life satisfaction among this population. Data were derived
      from the National Longitudinal Study of Adolescent Health (Add Health), a
      nationally representative probability sample of US adolescents. Bivariate and
      multivariable logistic regression was conducted to evaluate hypothesized
      predictors of global life satisfaction of Asian American adolescents. All
      analyses were conducted using STATA version 11. After exclusion of cases with
      missing values, 1021 Asian American adolescents were studied. Self- rated health,
      self-esteem, perceived neighborhood quality, parental support and peer support
      were significantly and positively related to better global life satisfaction.
      However, after controlling for other factors, only self-esteem (adjusted odds
      ratio [aOR]: 4.76; 95% confidence interval [CI]: 2.86-8.33) and perceived peer
      support (aOR: 2.76; 95% CI: 1.33-5.76) significantly predicted higher life
      satisfaction. Peer support and adolescents' self-concept are strongly correlated
      with Asian American adolescents' subjective well-being. To promote the wellness
      of this population, culturally sensitive strategies in developing peer
      relationship and healthy self-concept may be effective. More studies are needed
      for subgroup comparison of various ethnicities among Asian American adolescents. 

PMID- 25992313
TI  - Ocular cysticercosis with vitreous hemorrhage: a rare complication of a common
      disease.
AB  - INTRODUCTION: Cysticercosis, a helminthic infestation caused by Taenia solium,
      can produce central nervous system, muscles, visceral, subcutaneous tissues and
      skin manifestations. Ophthalmological involvement can affect eyelids,
      conjunctiva, anterior chamber, uvea, vitreous, retina, extraocular muscles and
      optic nerve. Simultaneous co-occurrence of intracranial and intraocular
      cysticercosis is a common presentation in clinical practice. CASE DESCRIPTION: We
      report a case of young girl who was diagnosed with multiple intracranial
      neurocysticercosis lesions and was on antiepileptic drugs, following which she
      presented with progressive painless vision loss from both the eyes. Indirect
      ophthalmoscopic examination showed evidence of subretinal cysts, retinal
      hemorrhage and retinal detachment in both the eyes. Surprisingly, bilateral
      vitreous hemorrhage was also detected. Ocular B-scan ultrasonography, orbital MRI
      and computed tomography revealed retinal detachment with vitreous hemorrhage in
      both the eyes. Magnetic resonance imaging (MRI) of brain showed multiple
      intraparenchymal small cystic lesions in bilateral cerebral and cerebellar
      hemispheres, basal ganglia, thalami and brainstem. CONCLUSIONS: Vitreous and
      retinal detachment are well known complications of intraocular cysticercosis,
      however, vitreous hemorrhage as preoperative feature has never been reported
      before, although vitreous hemorrhage as postoperative complication is common.

PMID- 25992314
TI  - Diagnostic values of chest pain history, ECG, troponin and clinical gestalt in
      patients with chest pain and potential acute coronary syndrome assessed in the
      emergency department.
AB  - In the assessment of chest pain patients with suspected acute coronary syndrome
      (ACS) in the emergency department (ED), physicians rely on global diagnostic
      impressions ('gestalt'). The aim of this study was to determine the diagnostic
      value of the ED physician's overall assessment of ACS likelihood, and the values
      of the main diagnostic modalities underlying this assessment, namely the chest
      pain history, the ECG and the initial troponin result. 1,151 consecutive ED chest
      pain patients were prospectively included. The ED physician's interpretation of
      the chest pain history, the ECG, and the global likelihood of ACS were recorded
      on special forms. The discharge diagnoses were retrieved from the medical
      records. A chart review was carried out to determine whether patients with a non
      ACS diagnosis at the index visit had ACS or suffered cardiac death within 30
      days. The gestalt was better than its components both at ruling in ("Obvious
      ACS", LR 29) and at ruling out ("No Suspicion of ACS", LR 0.01) ACS. In the
      "Strong suspicion of ACS" group, 60% of the patients did not have ACS. A positive
      TnT (LR 24.9) and an ischemic ECG (LR 8.3) were strong predictors of ACS and
      seemed superior to pain history for ruling in ACS. In patients with a normal TnT
      and non-ischemic ECG, chest pain history typical of AMI was not a significant
      predictor of AMI (LR 1.9) while pain history typical of unstable angina (UA) was
      a moderate predictor of UA (LR 4.7). Clinical gestalt was better than its
      components both at ruling in and at ruling out ACS, but overestimated the
      likelihood of ACS when cases were assessed as strong suspicion of ACS. Among the
      components of the gestalt, TnT and ECG were superior to the chest pain history
      for ruling in ACS, while pain history was superior for ruling out ACS. 

PMID- 25992315
TI  - Management of achilles tendon injury: A current concepts systematic review.
AB  - Achilles tendon rupture has been on the rise over recent years due to a variety
      of reasons. It is a debilitating injury with a protracted and sometimes
      incomplete recovery. Management strategy is a controversial topic and evidence
      supporting a definite approach is limited. Opinion is divided between surgical
      repair and conservative immobilisation in conjunction with functional orthoses. A
      systematic search of the literature was performed. Pubmed, Medline and EmBase
      databases were searched for Achilles tendon and a variety of synonymous terms. A
      recent wealth of reporting suggests that conservative regimens with early weight
      bearing or mobilisation have equivalent or improved rates of re-rupture to
      operative regimes. The application of dynamic ultrasound assessment of tendon gap
      may prove crucial in minimising re-rupture and improving outcomes. Studies
      employing functional assessments have found equivalent function between operative
      and conservative treatments. However, no specific tests in peak power, push off
      strength or athletic performance have been reported and whether an advantage in
      operative treatment exists remains undetermined. 

PMID- 25992316
TI  - Management of negative pressure wound therapy in the treatment of diabetic foot
      ulcers.
AB  - Diabetic foot (DF) is a common complication of diabetes and the first cause of
      hospital admission in diabetic patients. In recent years several guidelines have
      been proposed to reinforce the the management of DF with a notable increase in
      diabetes knowledge and an overall reduction of amputations. Significant
      improvements have been reached in the treatment of diabetic foot ulcers (DFUs)
      and nowadays clinicians have several advanced medications to apply for the best
      local therapy. Among these, negative pressure wound therapy (NPWT) is a useful
      adjunct in the management of chronic and complex wounds to promote healing and
      wound bed preparation for surgical procedures such as skin grafts and flap
      surgery. NPWT has shown remarkable results although its mechanisms of action are
      not completely understood. In this paper, we offer a complete overview of this
      medication and its implication in the clinical setting. We have examined
      literature related to NPWT concerning human, animal and in vitro studies, and we
      have summarized why, when and how we can use NPWT to treat DFUs. Further we have
      associated our clinical experience to scientific evidence in the field of
      diabetic foot to identify a defined strategy that could guide clinician in the
      use of NPWT approaching to DFUs. 

PMID- 25992317
TI  - Nerve compression and pain in human volunteers with narrow vs wide tourniquets.
AB  - AIM: To assess the clinical effects and the morphological grade of nerve
      compression. METHODS: In a prospective single-center randomized, open study we
      assessed the clinical effects and the morphological grade of nerve compression
      during 20 min of either a silicon ring (group A) or pneumatic tourniquet (group
      B) placement variantly on the upper non-dominant limb in 14 healthy human
      volunteers. Before and during compression, the median and radial nerves were
      visualized in both groups by 3 Tesla MR imaging, using high resolutional (2.5 mm
      slice thickness) axial T2-weighted sequences. RESULTS: In group A, Visual analog
      pain scale was 5.4 +/- 2.2 compared to results of group B, 2.9 +/- 2.5, showing a
      significant difference (P = 0.028). FPS levels in group A were 2.6 +/- 0.9
      compared to levels in group B 1.6 +/- 1, showing a significant difference (P =
      0.039). Results related to measureable effect on median and radial nerve function
      were equal in both groups. No undue pressure signs on the skin, redness or nerve
      damage occurred in either group. There was no significant difference in the
      diameters of the nerves without and under compression in either group on T2
      weighted images. CONCLUSION: Based on our results, no differences between narrow
      and wide tourniquets were identified. Silicon ring tourniquets can be regarded as
      safe for short time application.

PMID- 25992318
TI  - Surgical interventions for anterior shoulder instability in rugby players: A
      systematic review.
AB  - AIM: To systematically evaluate the evidence-based literature on surgical
      treatment interventions for elite rugby players with anterior shoulder
      instability. METHODS: We conducted a systematic review according to the PRISMA
      guidelines. A literature search was performed in PubMed, EMBASE and Google
      Scholar using the following search terms: "rugby" and "shoulder" in combination
      with "instability" or "dislocation". All articles published from inception of the
      included data sources to January 1(st) 2014 that evaluated surgical treatment of
      elite rugby players with anterior shoulder instability were examined. RESULTS:
      Only five studies were found that met the eligibility criteria. A total of 379
      shoulders in 376 elite rugby union and league players were included. All the
      studies were retrospective cohort or case series studies. The mean Coleman
      Methodological Score for the 5 studies was 47.4 (poor). Owing to heterogeneity
      amongst the studies, quantitative synthesis was not possible, however a detailed
      qualitative synthesis is reported. The overall recurrence rate of instability
      after surgery was 8.7%, and the mean return to competitive play, where reported,
      was 13 mo. CONCLUSION: Arthroscopic stabilization has been performed successfully
      in acute anterior instability and there is a preference for open Latarjet-type
      procedures when instability is associated with osseous defects.

PMID- 25992319
TI  - Endothelium-derived essential signals involved in pancreas organogenesis.
AB  - Endothelial cells (ECs) are essential for pancreas differentiation, endocrine
      specification, and endocrine function. They are also involved in the
      physiopathology of type 1 and type 2 diabetes. During embryogenesis, aortic ECs
      provide specific factors that maintain the expression of key genes for pancreas
      development such as pancreatic and duodenal homeobox-1. Other unknown factors are
      also important for pancreatic endocrine specification and formation of insulin
      producing beta cells. Endocrine precursors proliferate interspersed with ductal
      cells and exocrine precursors and, at some point of development, these endocrine
      precursors migrate to pancreatic mesenchyme and start forming the islets of
      Langerhans. By the end of the gestation and close to birth, these islets contain
      immature beta cells with the capacity to express vascular endothelial growth
      factor and therefore to recruit ECs from the surrounding microenvironment. ECs in
      turn produce factors that are essential to maintain insulin secretion in
      pancreatic beta cells. Once assembled, a cross talk between endocrine cells and
      ECs maintain the integrity of islets toward an adequate function during the whole
      life of the adult individual. This review will focus in the EC role in the
      differentiation and maturation of pancreatic beta cells during embryogenesis as
      well as the current knowledge about the involvement of endothelium to derive
      pancreatic beta cells in vitro from mouse or human pluripotent stem cells. 

PMID- 25992320
TI  - Are there new approaches for diagnosis, therapy guidance and outcome prediction
      of sepsis?
AB  - Beside many efforts to improve outcome, sepsis is still one of the most frequent
      causes of death in critically ill patients. It is the most common condition with
      high mortality in intensive care units. The complexity of the septic syndrome
      comprises immunological aspects - i.e., sepsis induced immunosuppression - but is
      not restricted to this fact in modern concepts. So far, exact mechanisms and
      variables determining outcome and mortality stay unclear. Since there is no
      typical risk profile, early diagnosis and risk stratification remain difficult,
      which hinders rapid and effective treatment initiation. Due to the heterogeneous
      nature of sepsis, potential therapy options should be adapted to the individual.
      Biomarkers like C-reactive protein and procalcitonin are routinely used as
      complementary tools in clinical decision-making. Beyond the acute phase proteins,
      a wide bunch of promising substances and non-laboratory tools with potential
      diagnostic and prognostic value is under intensive investigation. So far,
      clinical decision just based on biomarker assessment is not yet feasible.
      However, biomarkers should be considered as a complementary approach. 

PMID- 25992321
TI  - Spotlights on immunological effects of reactive nitrogen species: When
      inflammation says nitric oxide.
AB  - Over the last decades, nitric oxide (NO) has been definitively recognised as one
      of the key players involved in immunity and inflammation. NO generation was
      originally described in activated macrophages, which still represent the
      prototype of NO-producing cells. Notwithstanding, additional cell subsets
      belonging to both innate and adaptive immunity have been documented to sustain NO
      propagation by means of the enzymatic activity of different nitric oxide synthase
      isoforms. Furthermore, due to its chemical characteristics, NO could rapidly
      react with other free radicals to generate different reactive nitrogen species
      (RNS), which have been intriguingly associated with many pathological conditions.
      Nonetheless, the plethora of NO/RNS-mediated effects still remains extremely
      puzzling. The aim of this manuscript is to dig into the broad literature on the
      topic to provide intriguing insights on NO-mediated circuits within immune
      system. We analysed NO and RNS immunological clues arising from their biochemical
      properties, immunomodulatory activities and finally dealing with their impact on
      different pathological scenarios with far prompting intriguing perspectives for
      their pharmacological targeting. 

PMID- 25992322
TI  - Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C
      reactive protein.
AB  - Obstructive sleep apnea syndrome (OSAS) is a common medical condition, associated
      with atherosclerosis and cardiovascular disease (CVD). The underlying
      pathophysiologic mechanisms of this association have not been completely
      understood and may be multifactorial in origin. A number of studies suggest that
      inflammatory processes have emerged critical in the pathogenesis of CVD in OSAS.
      A range of circulating inflammatory molecules has been identified and measured,
      with a view to assess inflammation and predict vascular damage risk, such as
      plasma cytokines, adhesion molecules, and C-reactive protein (CRP). CRP is a
      relevant marker worthy of further study, because not only is elevated in patients
      with OSAS, but also is rapidly becoming a risk factor for cardiac disease.
      Furthermore, in selected OSAS patients, aggressive treatment of the disorder may
      lead to retarding or even improvement of CVD progression. However, still there is
      a debate on the true correlation between CRP and OSAS, as well as the clinical
      effect of any reduction after OSAS treatment. Further research is required to
      define those OSAS patients who will have a considerable reduction with treatment,
      as well as to understand the significance of the interaction between
      cardiovascular risk factor and CRP reduction in patients with OSAS. 

PMID- 25992324
TI  - Mood disorders: A potential link between ghrelin and leptin on human body?
AB  - Leptin and ghrelin are two hormones associated with multiple physiological
      functions, especially energy balance. Leptin is an adipocyte-secreted hormone
      discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone
      produced and secreted in the stomach. A number of previous studies showed that
      these hormones could be associated with different types of mood disorders. The
      results of previous studies, nevertheless, are confounded by diverse sample
      selection and different methodologies. A search for related articles in the
      PubMed database was attempted. The search covered studies, reports, reviews and
      editorials published in the last ten years. Older references served as auxiliary
      sources for comparison purposes. However, due to the different results of the
      studies, there is a need for more investigation in order to establish the exact
      biochemical mechanisms that are responsible for these diseases and ghrelin's and
      leptin's effects on mood. 

PMID- 25992326
TI  - Electrophysiological neuromonitoring of the laryngeal nerves in thyroid and
      parathyroid surgery: A review.
AB  - Recurrent laryngeal nerve (RLN) injury is one of the most common complications of
      thyroid surgery. Injury to the external branch of the superior laryngeal nerve is
      less obvious and affects the voice variably; however, it can be of great
      significance to professional voice users. Recent literature has led to an
      increase in the use of neuromonitoring as an adjunct to visual nerve
      identification during thyroid surgery. In our review of the literature, we
      discuss the application, efficacy and safety of neuromonitoring in thyroid
      surgery. Although intraoperative neuromonitoring (IONM) contributes to the
      prevention of laryngeal nerves injury, there was no significant difference in the
      incidence of RLN injury in thyroid surgery when IONM was used compared with
      visual identification alone. IONM use is recommended in high risk patients;
      however, there are no clear identification criteria for what constitutes "high
      risk". There is no clear evidence that IONM decreases the risk of laryngeal nerve
      injury in thyroid surgery. However, continuous IONM provides a promising tool
      that can prevent imminent nerve traction injury by detecting decreased amplitude
      combined with increased latency. 

PMID- 25992327
TI  - Genetic test in multiple endocrine neoplasia type 1 syndrome: An evolving story.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited
      tumour syndrome expressing various endocrine and non-endocrine lesions and
      tumours. Since the identification of the causative gene, the oncosuppressor gene
      MEN1, in 1997, genetic testing has revealed an important approach for the early
      and differential diagnosis of the disease. The finding of a MEN1 mutation in a
      patient has important clinical implications for relatives since it allows very
      early disease diagnosis and identification of carriers, even before biochemical
      and/or clinical manifestation, permitting their inclusion in a specific program
      of surveillance and subsequent praecox therapy. Currently, genetic testing for
      MEN1 consists principally of the sequencing of coding regions and intron-exon
      junctions of the MEN1 gene. However, the recent acquisition of novel high
      throughput technologies will allow the design of innovative, accurate, complete
      and rapid genetic diagnosis. These new tools are able to increase the strength of
      the analysis and almost completely eliminate the possibility of false negative
      results. This review aims to give an overview on genetic testing of MEN1
      syndrome, reporting the positive aspects of performing the analysis and the
      future perspectives for improving the performance of the test, as well as its
      application in clinical practice. 

PMID- 25992325
TI  - Asymmetric dimethylarginine, a biomarker of cardiovascular complications in
      diabetes mellitus.
AB  - Cardiovascular (CV) complications are an essential causal element of prospect in
      diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor
      for prospective crisis of coronary artery diseases and/or cerebral infarction in
      DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has
      been established as an inhibitor of endogenous nitric oxide synthesis and the
      relationship between ADMA and arteriosclerosis has been reported. In our study
      with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV
      risk factors are the useful predictors of DMCV complications. After the
      measurement of the respective CV risk factors, we have followed the enrolled T2DM
      patients for 5 years. We have finally analyzed 77 patients. DMCV complications
      developed in 15 cases newly within 5 years, and 4 cases recurred. The
      concentrations of ADMA in plasma were markedly more elevated in 19 DM patients
      with CV complications than in 58 DM patients without CV complications. Urinary
      albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index
      (ABI) were also higher in patients with CV complications. Multiple regression
      analyses showed that U-Alb had an influence on the high level of ADMA
      (standardized beta = 6.59, P = 0.00014) independently of age, systolic BP,
      fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is
      presently known regarding plasma ADMA that might be a new and meaningful
      biomarker of CV complications in DM subjects. 

PMID- 25992328
TI  - Does physical therapy and rehabilitation improve outcomes for diabetic foot
      ulcers?
AB  - One of the most common and serious complications of diabetes mellitus is
      ulceration of the foot. Among persons with diabetes, 12%-25% will present to a
      healthcare institution for a foot disorder during their lifespan. Despite
      currently available medical and surgical treatments, these are still the most
      common diabetes-related cause of hospitalization and of lower extremity
      amputations. Thus, many adjunctive and complementary treatments have been
      developed in an attempt to improve outcomes. We herein review the available
      literature on the effectiveness of several treatments, including superficial and
      deep heaters, electro-therapy procedures, prophylactic methods, exercise and shoe
      modifications, on diabetic foot wounds. Overall, although physical therapy
      modalities seem to be useful in the treatment of diabetic foot wounds, further
      randomized clinical studies are required. 

PMID- 25992323
TI  - Role of the Wnt/beta-catenin pathway in gastric cancer: An in-depth literature
      review.
AB  - Gastric cancer remains one of the most common cancers worldwide and one of the
      leading cause for cancer-related deaths. Gastric adenocarcinoma is a
      multifactorial disease that is genetically, cytologically and architecturally
      more heterogeneous than other gastrointestinal carcinomas. The aberrant
      activation of the Wnt/beta-catenin signaling pathway is involved in the
      development and progression of a significant proportion of gastric cancer cases.
      This review focuses on the participation of the Wnt/beta-catenin pathway in
      gastric cancer by offering an analysis of the relevant literature published in
      this field. Indeed, it is discussed the role of key factors in Wnt/beta-catenin
      signaling and their downstream effectors regulating processes involved in tumor
      initiation, tumor growth, metastasis and resistance to therapy. Available data
      indicate that constitutive Wnt signalling resulting from Helicobacter pylori
      infection and inactivation of Wnt inhibitors (mainly by inactivating mutations
      and promoter hypermethylation) play an important role in gastric cancer.
      Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in
      gastric cancer. The identification of specific membrane, intracellular, and
      extracellular components of the Wnt pathway has revealed potential targets for
      gastric cancer therapy. High-throughput "omics" approaches will help in the
      search for Wnt pathway antagonist in the near future. 

PMID- 25992329
TI  - Barriers in contribution of human mesenchymal stem cells to murine muscle
      regeneration.
AB  - AIM: To study regeneration of damaged human and murine muscle implants and the
      contribution of added xenogeneic mesenchymal stem cells (MSCs). METHODS: Minced
      human or mouse skeletal muscle tissues were implanted together with human or
      mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined
      immunodeficient mice. The muscle tissues (both human and murine) were minced with
      scalpels into small pieces (< 1 mm(3)) and aliquoted in portions of 200 mm(3).
      These portions were either cryopreserved in 10% dimethylsulfoxide or freshly
      implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly
      before implantation. Implants were collected at 7, 14, 30 or 45 d after
      transplantation and processed for (immuno)histological analysis. The progression
      of muscle regeneration was assessed using a standard histological staining
      (hematoxylin-phloxin-saffron). Antibodies recognizing Pax7 and von Willebrand
      factor were used to detect the presence of satellite cells and blood vessels,
      respectively. To enable detection of the bone marrow-derived MSCs or their
      derivatives we used MSCs previously transduced with lentiviral vectors expressing
      a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect
      beta-galactosidase-positive cells and myofibers. RESULTS: Myoregeneration in
      implants of fresh murine muscle was evident as early as day 7, and progressed
      with time to occupy 50% to 70% of the implants. Regeneration of fresh human
      muscle was slower. These observations of fresh muscle implants were in contrast
      to the regeneration of cryopreserved murine muscle that proceeded similarly to
      that of fresh tissue except for day 45 (P < 0.05). Cryopreserved human muscle
      showed minimal regeneration, suggesting that the freezing procedure was
      detrimental to human satellite cells. In fresh and cryopreserved mouse muscle
      supplemented with LacZ-tagged mouse MSCs, beta-galactosidase-positive myofibers
      were identified early after grafting at the well-vascularized periphery of the
      implants. The contribution of human MSCs to murine myofiber formation was,
      however, restricted to the cryopreserved mouse muscle implants. This suggests
      that fresh murine muscle tissue provides a suboptimal environment for maintenance
      of human MSCs. A detailed analysis of the histological sections of the various
      muscle implants revealed the presence of cellular structures with a deviating
      morphology. Additional stainings with alizarin red and alcian blue showed
      myofiber calcification in 50 of 66 human muscle implants, and encapsulated
      cartilage in 10 of 81 of murine muscle implants, respectively. CONCLUSION: In
      mouse models the engagement of human MSCs in myoregeneration might be
      underestimated. Furthermore, our model permits the dissection of species-specific
      factors in the microenvironment.

PMID- 25992330
TI  - Development of pyogenic granuloma and hemangioma after placement of dental
      implants: A review of literature.
AB  - AIM: The aim of this study is to highlight the development of pyogenic granuloma
      and hemangioma after the placement of dental implants. MATERIALS AND METHODS: A
      literature search was performed using MEDLINE, accessed via the National Library
      of Medicine PubMed Interface, for articles published between 2000 and 2014 in
      English, relating to the occurrence of pyogenic granuloma or hemangioma in
      relation to dental implants. RESULTS: Our search identified only four case
      reports of pyogenic granuloma and hemangioma related to dental implants as
      reported in the English literature. CONCLUSION: Placement of dental implants can
      cause development of pyogenic granuloma and hemangioma, indicating that placement
      of dental implants requires well-trained specialists with perfect skills in
      dental implantology. Furthermore, the critical selection of the appropriate case
      is of paramount importance to avoid the occurrence of such complications.

PMID- 25992331
TI  - Probiotics: Healthy bugs and nourishing elements of diet.
AB  - The use of probiotics is based on the concept that adding the right live microbes
      to the complex human system can result in physiological benefits. The benefit of
      fermented milk in human diet has been acknowledged since Vedic times; however,
      the scientific interest in this field was evoked by Ellie Metchinkoff who
      recommended that people should consume fermented milk containing lactobacilli to
      prolong their lives, as accelerated aging is due to autointoxication caused by
      the toxins produced by the gut microflora. They have been used to improve
      gastrointestinal health and their attractiveness has evinced interest to study
      their role in the promotion of oral health also. Studies have been widely carried
      out to establish the role of intestinal lactobacilli as probiotic to treat
      various gastrointestinal disorders, but only limited studies are available on the
      oral use of probiotics. The probiotic products usually contain lactobacilli and
      bifidobacteria, and their demand in the market is growing day by day. This paper
      provides an overview of various studies in the literature that emphasize on the
      role of probiotics to combat oral diseases and encourages more research in this
      field. 

PMID- 25992332
TI  - Effect of preoperative oral midazolam sedation on separation anxiety and
      emergence delirium among children undergoing dental treatment under general
      anesthesia.
AB  - AIM: To investigate the possible effects of preoperative oral Midazolam on
      parental separation anxiety, emergence delirium, and post-anesthesia care unit
      time on children undergoing dental rehabilitation under general anesthesia.
      METHODS: Randomized, prospective, double-blind study. Seventy-eight American
      Society of Anesthesiology (ASA) I children were divided into two groups of 39
      each. Children of the first group were premedicated with oral Midazolam 0.5
      mg/kg, while children of the control group were premedicated with a placebo.
      Scores for parental separation, mask acceptance, postoperative emergence
      delirium, and time spent in the post-anesthesia care unit were compared
      statistically. RESULTS: The test group showed significantly lower parental
      separation scores and high acceptance rate for anesthetic mask. There was no
      significant difference between the two groups regarding emergence delirium and
      time spent in post-anesthesia care unit. CONCLUSIONS: Preoperative oral Midazolam
      could be a useful adjunct in anxiety management for children suffering dental
      anxiety. The drug may not reduce the incidence of postoperative emergence
      delirium. The suggested dose does not seem to affect the post-anesthesia care
      unit time.

PMID- 25992333
TI  - Prevalence of early childhood caries and its risk factors in 18-72 month old
      children in Salem, Tamil Nadu.
AB  - BACKGROUND: Early childhood caries (ECC) is one of the most common dental
      diseases among the preschoolers, leading to suboptimal health. A study was
      planned to evaluate the prevalence of ECC in preschool children in the age group
      between 18 and 72 months and its relationship with parent's education and
      socioeconomic status of the family. MATERIALS AND METHODS: This cross-sectional
      study was conducted among 2771 children selected randomly, in the age group 18-72
      months and attending playschools and primary schools in urban, semi-urban, and
      rural areas of Salem, Tamil Nadu. A modified Winter et al. questionnaire and a
      proforma were used for collecting information on each child. The completed
      questionnaire and proformas were statistically analyzed and evaluated. The
      statistical analysis was done using Student's t-test and analysis of variance
      (ANOVA) to obtain mean values. RESULTS: The prevalence of ECC in Salem was 16%
      with a mean dfs of 5.23 +/- 1. Prevalence was high among the children of low
      socioeconomic status group and the children of working mothers, with a mean dfs
      of 10.47. CONCLUSION: The prevalence of ECC was 16% in Salem, Tamil Nadu. ECC was
      seen more in children of working mothers, lower parental education, and lower
      socioeconomic groups.

PMID- 25992334
TI  - Significance of maternal periodontal health in preeclampsia.
AB  - OBJECTIVE: The aim of the present case-control study was to evaluate the
      association between maternal periodontitis and preeclampsia. Association studies
      between maternal periodontitis and elevated risk for preeclampsia have shown
      conflicting results. Periodontal maintenance is necessary to reduce the risk of
      adverse pregnancy outcomes like preeclampsia. MATERIALS AND METHODS: Periodontal
      parameters [bleeding on probing, probing depth (PD), and clinical attachment
      level (CAL)] of 1320 women were assessed, followed by retrieval of their
      demographic and medical data from the medical records. Based on the medical
      records, 80 women were excluded from the study, leaving 1240 females as the
      eligible sample for the study. The women were divided into control group (1120
      non-preeclamptic women who gave birth to infants with adequate gestational age)
      and case group (120 preeclamptic women). Logistic regression analysis revealed
      that primiparity and maternal periodontitis were the two significant variables
      causing preeclampsia. Further analysis was carried out by matching the two groups
      for primiparity to find the significance of maternal periodontitis. Maternal
      periodontitis was defined as PD >=4 mm and CAL >=3 mm at the same site in at
      least four teeth. RESULTS: The results showed that maternal periodontitis (odds
      ratio 19.8) was associated with preeclampsia. Maternal periodontitis also
      remained associated with preeclampsia after matching for primiparity, which was
      another significant confounding factor in the study (odds ratio 9.33).
      CONCLUSION: Maternal periodontitis is a risk factor associated with preeclampsia,
      emphasizing the importance of periodontal care in prenatal programs.

PMID- 25992335
TI  - Evaluation of knowledge and attitude of school teachers about emergency
      management of traumatic dental injury.
AB  - INTRODUCTION: Traumatic dental injuries (TDIs) are widespread in the population
      and are a serious dental public health problem among children. Dental trauma may
      cause both functional and esthetic problems, with possible impacts on the
      patient's quality of life. AIM: To investigate teacher's knowledge and attitudes
      of Mathura city about emergency management of TDIs in children. MATERIALS AND
      METHODS: A total of 352 teachers from total 23 schools of Mathura city were
      included in the study. Data were collected through a survey, which included a
      self-administered questionnaire. The questionnaire consisted of three major parts
      containing multiple-choice questions. RESULTS: Among the teachers 51.1% were
      males and 48.9% were females. Majority of the respondents, that is, 33.5% were
      between 31 and 40 years of age. Most respondents (34%) had more than 10 years of
      teaching experience. Majority of the teachers (39.2%) had educational
      qualification other than B.Ed. and M.Ed. degrees. Physical education teachers
      comprised the largest group of school teachers. Regarding knowledge and attitude,
      the teachers with 10-20 years of teaching experience, physical education
      teachers, and the teachers other than B.Ed. and M.Ed. qualifications had given
      more correct answers to the questions when compared with other groups.
      CONCLUSION: For the teachers having a low level of knowledge, there is a need for
      greater awareness to improve teachers' knowledge and attitudes related to the
      emergency management of TDIs in children by organizing educative and motivational
      programs.

PMID- 25992336
TI  - Bactericidal activity of propylene glycol, glycerine, polyethylene glycol 400,
      and polyethylene glycol 1000 against selected microorganisms.
AB  - AIM: The aim of the present study was to evaluate the bactericidal activity of
      propylene glycol, glycerine, polyethylene glycol 400 (PEG 400), and polyethylene
      glycol 1000 (PEG 1000) against selected microorganisms in vitro. MATERIALS AND
      METHODS: Five vehicles, namely propylene glycol, glycerine, PEG 400, PEG 1000,
      and combination of propylene glycol with PEG 400, were tested for their
      bactericidal activity. The minimum bactericidal concentration was noted against
      four standard strains of organisms, i.e. Streptococcus mutans American Type
      Culture Collection (ATCC) 25175, Streptococcus mutans ATCC 12598, Enterococcus
      faecalis ATCC 35550, and Escherichia coli ATCC 25922, using broth dilution assay.
      Successful endodontic therapy depends upon thorough disinfection of root canals.
      In some refractory cases, routine endodontic therapy is not sufficient, so
      intracanal medicaments are used for proper disinfection of canals. Intracanal
      medicaments are dispensed with vehicles which aid in increased diffusion through
      the dentinal tubules and improve their efficacy. Among the various vehicles used,
      glycerine is easily available, whereas others like propylene glycol and
      polyethylene glycol have to be procured from appropriate sources. Also, these
      vehicles, being viscous, aid in sustained release of the medicaments and improve
      their handling properties. The most commonly used intracanal medicaments like
      calcium hydroxide are ineffective on many microorganisms, while most of the other
      medicaments like MTAD (Mixture of Tetracycline, an Acid, and a Detergent) and
      Triple Antibiotic Paste (TAP) consist of antibiotics which can lead to
      development of antibiotic resistance among microorganisms. Thus, in order to use
      safer and equally effective intracanal medicaments, newer alternatives like
      chlorhexidine gluconate, ozonized water, etc., are being explored. Similarly, the
      five vehicles mentioned above are being tested for their antimicrobial activity
      in this study. RESULTS: All vehicles exhibited bactericidal activity at 100%
      concentration. CONCLUSION: Propylene glycol was effective against three organisms
      namely S. mutans E. faecalis and E. coli and its bactericidal activity was at
      50%, 25% and 50% respectively. PEG 1000 was effective against S. mutans and E.
      coli at 25%. Hence propylene glycol was effective on more number of organisms of
      which E. faecalis is a known resistant species. PEG 1000 was bactericidal at a
      lower concentration but was effective on two organisms only.

PMID- 25992337
TI  - "Education level" responsible for inequities in oral practices among 15-34-year
      old individuals in Jizan, Saudi Arabia.
AB  - BACKGROUND: Education plays an important role and is a second major (non-medical
      dimensional) factor influencing the health status. Individuals demonstrate oral
      practices that impact the oral health positively or negatively. This study
      analyzes how self-reported oral practices are influenced by different educational
      levels among young adults in Jizan. MATERIALS AND METHODS: The survey was
      conducted in four areas around University of Jizan. The survey subjects, aged
      between 15 and 34 years, completed the self-administered, structured
      questionnaire. Inter-group comparison was done using Chi-square test. Level of
      significance was fixed at P < 0.05. RESULTS: Exactly 1597 subjects completed the
      survey. Of these, 644 (40.3%) had attained higher education, 884 (55.4%) had
      lower education, and 69 (4.3%) were illiterate. Statistical comparisons showed
      significant differences among the three groups with respect to the use of
      toothbrushes (chi(2) = 88.67, P < 0.001), use of interdental cleaning aids
      (chi(2) = 15.04, P < 0.001), siwak use (chi(2) = 16.31, P < 0.001), cigarette
      smoking (chi(2) = 14.28, P < 0.001), and khat chewing (chi(2) = 38.1, P < 0.001).
      Siwak use was more among those with low educational level and illiterates.
      Further, smoking and khat chewing were significantly more prevalent among
      illiterates. CONCLUSION: The subjects with low education and the illiterates
      exercise harmful oral practices. This study indicates that educational level is
      responsible for inequities in oral practices.

PMID- 25992338
TI  - Bacteriological evaluation of Allium sativum oil as a new medicament for
      pulpotomy of primary teeth.
AB  - OBJECTIVE: To compare the effects of Allium sativum oil and formocresol on the
      pulp tissue of the pulpotomized teeth. MATERIALS AND METHODS: Twenty children
      were selected for this study. All children had a pair of non-vital primary
      molars. A sterile paper point was dipped in the root canals prior to the mortal
      pulpotomy. These paper points were collected in transfer media and immediately
      transported to the microbiological lab to be investigated microbiologically (for
      Streptococcus mutans and Lactobacillus acidophilus). Then the procedure of mortal
      pulpotomy was performed. After 2 weeks, the cotton pellets were removed and
      sterile paper points were dipped in the root canals for microbiological
      examination. Then comparison between the count of bacteria before and after
      treatment was conducted. Statistical analysis was performed using independent t
      test and paired t-test at the significance level of alpha = 0.05. RESULTS: After
      application of both medicaments, there was a marked decrease in S. mutans and L.
      acidophilus counts. The difference between the mean of log values of the count
      before and after the application was highly significant for both medicaments (P <
      0.05); however, better results were obtained when A. sativum oil was used.
      CONCLUSION: A. sativum oil had more powerful antimicrobial effects than
      formocresol on the bacteria of the infected root canals.

PMID- 25992339
TI  - Effectiveness of the supraomohyoid neck dissection in clinically N0 neck patients
      with squamous cell carcinoma of buccal mucosa and gingivobuccal sulcus.
AB  - BACKGROUND: To evaluate the effectiveness of the supraomohyoid neck dissection in
      clinically N0 neck patients with squamous cell carcinoma of buccal mucosa and
      gingivobuccal sulcus. MATERIALS AND METHODS: This was a prospective study of five
      patients with squamous cell carcinoma of gingivobuccal mucosa of oral cavity with
      clinically N0 neck, conducted over a period of 2 years from July 2007 to Oct 2009
      in the Department of Oral and Maxillofacial Surgery, Narayana Dental College and
      Hospital. The study was conducted in patients irrespective of age, sex, size,
      thickness, and type of differentiation of the lesion. All patients have
      clinically non-palpable lymphnodes (N0 neck), while patients with palpable
      lymphnodes, patients with previous surgery, and patients with previous
      radiotherapy were excluded from the study. RESULTS: Level I was the commonest
      site of neck metastasis in our study. Among the five patients, two (40%) patients
      (case 2 and 3) had occult cervical metastasis (level IB nodes are
      histopathologically positive nodes) and the remaining three patients (60%) had no
      occult cervical metastasis. The recurrence rate was 20% for patients who received
      postoperative radiotherapy. There was no morbidity and postoperative dysfunction
      and the mortality rate was only 20% in our study. CONCLUSION: Supraomohyoid neck
      dissection is the therapeutic procedure in clinically N0 neck patients with
      squamous cell carcinoma of buccal mucosa and gingivobuccal sulcus of mandible.
      Supraomohyoid neck dissection, when indicated, contributes to the concept of less
      invasive surgery and offers functional and aesthetic advantages without
      compromising the clearance with minimal morbidity.

PMID- 25992340
TI  - Perception and attitudes versus medical writing skills.

PMID- 25992341
TI  - Histopathological differentiation of oral squamous cell carcinoma and salivary
      lactate dehydrogenase: A biochemical study.
AB  - CONTEXT: Early diagnosis of oral cancer is a priority health objective, in which
      oral health professionals may play a pivotal role. Detection should lead to less
      damage from cancer therapy and to a better prognosis. AIMS: The aim was to
      estimate and compare the salivary lactate dehydrogenase (LDH) levels in various
      histological differentiation of oral squamous cell carcinoma (OSCC) patients and
      normal subjects. SETTINGS AND DESIGN: Hospital-based setting, case-control study.
      SUBJECTS AND METHODS: A case-control study was undertaken comprising 30 OSCC
      patients and 30 healthy controls. The OSCC patients were grouped into well
      differentiated, moderately differentiated and poorly differentiated OSCC based on
      their histological tumor differentiation. Unstimulated whole saliva was
      collected, assayed for LDH levels using a standard kit and measured
      spectrophotometrically at 340 nm. STATISTICAL ANALYSIS USED: The results obtained
      were subjected to statistical analysis using Kruskal-Wallis and Mann-Whitney U
      tests. Spearman's correlation was used to correlate the histological tumor
      differentiation with the salivary LDH levels. RESULTS: The mean salivary LDH
      levels in the control group, well-differentiated OSCC group, moderately
      differentiated OSCC group, and poorly differentiated OSCC group were 117.33 +/-
      19.37 IU/L, 355.83 +/- 16.73 IU/L, 484.18 +/- 25.84 IU/L, and 620.35 +/- 18.69
      IU/L, respectively. The difference in the mean salivary LDH levels was
      statistically significant among the various groups (Kruskal-Wallis chi(2) =
      50.820, P < 0.001). Spearman's correlation showed significant difference between
      salivary LDH levels and histological differentiation of OSCC (r = -0.689, P <
      0.01). CONCLUSIONS: The salivary LDH levels were higher in OSCC patients when
      compared to the healthy controls. The salivary LDH levels were found to be the
      highest among the poorly differentiated OSCC.

PMID- 25992342
TI  - Locally advanced oral cavity squamous cell carcinoma: Barriers related to
      effective treatment.
AB  - BACKGROUND: Oral cavity cancer is a significant health problem in India. Majority
      of patients present with locally advanced disease requiring multimodality
      treatment. Compliance to recommended treatment is an important factor affecting
      outcome. AIMS: The aim was to evaluate the outcome of locally advanced oral
      cavity cancer patients with regards to treatment adherence and to assess reasons
      of noncompliance. MATERIALS AND METHODS: This was a prospective observational
      study. We included patients referred to Department of Medical Oncology for
      induction chemotherapy in view of locally advanced oral cavity cancer. RESULTS:
      Only 15 (26%) patients completed planned treatment schedule. Their 1 year overall
      survival was 93%. The remaining 43 patients who received inadequate treatment had
      a dismal 21% 1 year overall survival. Illiteracy, poverty, long waiting list for
      surgery, prolonged delay for health scheme treatment plan approval and
      dissatisfaction with attitude of hospital staffs are major barriers related to
      effective treatment of these patients. CONCLUSIONS: A detailed discussion with
      patient and their relatives regarding recommended treatment, proper
      implementation of health schemes, increasing trained manpower to avoid long
      waiting list for surgery, provision of additional financial support for family
      member accompanying the patient and a sympathetic approach toward patients are
      needed to help these patients overcome the battle.

PMID- 25992343
TI  - Knowledge, attitude and practices about oral cancers among dental students in H.P
      Government Dental College, Shimla-Himachal Pradesh.
AB  - AIM: The aim was to assess the knowledge, attitude and practices among
      undergraduate dental students about oral cancer. MATERIALS AND METHODS: A cross
      sectional questionnaire study was conducted among undergraduate dental students
      between the 3rd and 5th years in H.P Government Dental College, Shimla. The
      questionnaire consisted of 15 questions, five each on knowledge, attitudes and
      practices. The data were analyzed by Statistical Package for the Social Sciences
      (SPSS Inc., version 16 for Windows, Chicago, IL, USA). RESULTS: The response rate
      of the study was 90.6%. There were 23 (21.5%) males and 84 (78.5%) females in the
      study. There was a predominance of females (78.5%). The average knowledge
      percentage for the entire population is 81.9% (excellent knowledge). Tobacco and
      alcohol were correctly identified by 63.5% of the subjects. Squamous cell
      carcinoma was described as the most common type of oral cancer by 105 (98.3%) of
      the students. 60.7% of the subjects strongly disagreed that their knowledge
      regarding the prevention and detection of oral cancer is current and adequate,
      and 99% agreed that there is a need for additional training/information regarding
      oral cancer. About 92.5% of the subjects used to educate their subjects about the
      harmful effects of tobacco and alcohol. CONCLUSION: The study implies that the
      knowledge, especially about the etiological factors of oral cancer needs to be
      reinforced throughout the undergraduate dental courses so that they can use the
      same in educating and motivating the masses to adapt healthy lifestyles.

PMID- 25992344
TI  - Pancytopenia - (?) An obstacle in the diagnosis and outcome of pediatric acute
      lymphoblastic leukemia.
AB  - CONTEXT: Acute lymphoblastic leukemia (ALL) ranks first among pediatric
      malignancies. 8-12% of ALL present with pancytopenia and 2% with hypocellular
      marrow a. Diagnosis of ALL in the background of pancytopenia and aplastic bone
      marrow is difficult. AIMS: This study was aimed to compare the clinicopathologic,
      genetic, and outcome of paediatric ALL patients with and without pancytopenia.
      SETTINGS AND DESIGN: This is a retrospective cross-sectional study. SUBJECTS AND
      METHODS: The study included all ALL patients presenting with pancytopenia. The
      control group included equal number of randomly selected patients with ALL
      without pancytopenia treated during the same period. Ethics committee approved
      this study. The demographic, laboratory, and treatment-related details were
      retrieved from the records and entered in an Excel sheet. STATISTICAL ANALYSIS
      USED: Data was analyzed with Chi-square test with IBM SPSS statistics 16
      software. RESULTS: Diagnosis by peripheral smear is significantly lower (P =
      0.015) in comparison with the control group. There is no significant difference
      in diagnosis between the groups by bone marrow aspirate (P = 0.731) and biopsy (P
      = 0.849). The diagnosis of leukemia is misdiagnosed as hypo cellular/aplastic
      marrow in 10% of the pancytopenic patients. Flow cytometry yielded the diagnosis
      in all the pancytopenic patients. Though cytogenetic abnormalities are more
      common in pancytopenic group, it is not statistically significant (P = 0.106).
      There is no significant difference in treatment outcome between the groups (P =
      0.0827%). CONCLUSIONS: Clinical expertise is highly essential to evaluate a case
      of pancytopenia to diagnose leukemia. Pancytopenia is an obstacle in the
      diagnosis of ALL without immunophenotyping. There is no significant difference in
      the outcome between the two groups.

PMID- 25992345
TI  - Clinical significance of thymidine kinase in Egyptian children with acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood
      malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK
      1) is expressed in proliferating cells so elevated TK-1 indicates active tumor
      growth. OBJECTIVE: To study the clinical significance of TK-1 in children with
      ALL. PATIENTS AND METHODS: This study was carried out on 40 children with newly
      diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta
      University (26 males and 14 females) with their ages ranged from 4 to 10 years
      and 30 healthy children of matched age and sex as a control group. For all
      patients the following were done: Complete blood picture, bone marrow
      examination, immunophenotyping and TK-1 serum levels. RESULTS: Mean TK-1 level
      was significantly higher in patients at diagnosis than controls and significantly
      higher in patients with unfavorable outcome than patients with favorable outcome.
      Mean TK-1 level was significantly higher in patients in relapse than patients in
      remission and controls. No significant differences in mean TK-1 level between
      patients in remission and controls. There were statistically significant
      differences in disease free survival and overall survival between patients with
      favorable and unfavorable outcome. CONCLUSION: From this study we concluded that
      TK is a helpful marker in diagnosis and follow-up of patients with ALL.
      RECOMMENDATIONS: Thymidine kinase-1 should be routinely assessed at diagnosis and
      during follow-up in ALL patients for better diagnostic and prognostic assessment
      and should be taken in consideration in designing future therapeutic strategies
      based on patients-specific risk factors.

PMID- 25992346
TI  - Knowledge, attitude, and awareness of childhood cancer among undergraduate
      medical students in South India.
AB  - BACKGROUND: In India roughly 60000 childhood cancer cases are diagnosed annually
      with only nearly 100 pediatric oncologists. So it's pertinent that the physicians
      and pediatricians are adequately equipped to recognize and refer them
      appropriately. Hence this study was conducted to assess the knowledge, attitude
      and awareness of childhood cancer among undergraduate medical students in South
      India. MATERIALS AND METHODS: The study was conducted among 240 undergraduate
      students from all over South India in a undergraduate pediatric clinical
      training. A 24 point questionnaire was given to assess their understanding of
      pediatric malignancies and their interest towards pediatric oncology. Statistical
      analysis was done with SPSS 18.V software. RESULTS: 50% were interested in
      pursuing pediatrics as their career but 80% of them were not interested in
      pursuing pediatric oncology as their career. 55% of the students have not
      encountered any pediatric oncology patients in the ward. 40% did not have any
      lecture classes on pediatric oncology. 65.5% felt that their knowledge of
      childhood cancer did not make them competent to suspect and refer appropriately
      during their practice. 84% supported that there is a need to improve pediatric
      oncology teaching in their medical curriculum. CONCLUSIONS: The study
      unambiguously states that the future physicians lack confidence in identifying
      and managing childhood malignancies and pediatric oncology is far down in their
      career options. There is a need to reform the undergraduate medical students by
      increasing their exposure to pediatric oncology to improve their competence
      levels and interest in pursuing it as a career also.

PMID- 25992347
TI  - Expression of inducible nitric oxide synthase in carcinomas and sarcomas
      affecting the oral cavity.
AB  - CONTEXT: Inducible nitric oxide synthase (iNOS) is a cytoplasmic enzyme which
      plays a crucial role in the pathogenesis of oral carcinomas and sarcomas. AIMS:
      The objective of this study was to analyze the immunohistochemical expression of
      iNOS in carcinomas and sarcomas affecting the oral cavity in order to understand
      the possible role of iNOS in their biologic behavior and to correlate iNOS
      expression with lymph node metastasis in carcinomas and sarcomas. SETTINGS AND
      DESIGN: Patients, who attended the oral diagnosis department of Vinayaka Missions
      Sankarachariyar Dental College, were screened, for the purpose of the study.
      Besides these, paraffin-embedded tissue blocks were also retrieved from archives
      of the Oral and Maxillofacial Pathology Department. A total of 40 cases (20
      carcinomas and 20 sarcomas) were selected for the study. SUBJECTS AND METHODS: A
      total of 40 cases (20 carcinomas and 20 sarcomas) were selected for the study.
      Five apparently normal tissues were obtained from the tumor adjacent normal
      tissue to be used as a control. These were subjected to immunohistochemical
      staining using antibody to iNOS and evaluated. STATISTICAL ANALYSIS USED: The
      results were analyzed using the Chi-square test. RESULTS: Among the 20 carcinomas
      19 showed a positive immunoreactivity for iNOS and 1 case was negative. Among the
      19 immunopositive iNOS cases of carcinomas, 15 cases showed positive lymph node
      metastasis. Among the sarcomas, positive immunoreactivity for iNOS was seen in 10
      hard tissue sarcomas, while the remaining 10 soft tissue sarcomas were negative
      for iNOS expression. The results were analyzed using the Chi-square test.
      CONCLUSIONS: iNOS is a reliable marker for lymph node metastasis in carcinomas
      irrespective of the histologic grade. The high expression in carcinomas shows
      that the carcinomas elaborate more angiogenesis for growth compared with the
      sarcomas with the exception of hard tissue sarcomas.

PMID- 25992348
TI  - Anticancer activity of Cynodon dactylon L. root extract against diethyl
      nitrosamine induced hepatic carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma is one of the most common cancers and a
      lethal disease. In view of the limited treatment and a grave prognosis of liver
      cancer, preventive control has been emphasized. MATERIALS AND METHODS: The
      methanolic extract of roots of Cynodon dactylon was screened for its hepato
      protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss
      albino mice. The plant extract at a dose of 50 mg/kg was administered orally once
      a week, up to 30 days after DEN administration. The animals were sacrificed;
      blood sample and liver tissue were collected and used for enzyme assay such as,
      asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase
      (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The
      liver marker enzymes AST and ALT produced significant results in the protective
      action. RESULTS: The antioxidant enzyme assay results concerning the improved
      activity of GPx, GST and CAT. These results concluded that enhanced levels of
      antioxidant enzyme and reduced amount of serum amino transaminase, which are
      suggested to be the major mechanisms of C. dactylon root extract in protecting
      the mice from hepatocarcinoma induced by DEN. These biochemical observations were
      supplemented by histopathological examination of liver sections. CONCLUSION: The
      methanolic extract of C. dactylon possesses significant anticancer properties.

PMID- 25992349
TI  - Correlation of p53 immunoexpression with DNA ploidy and apoptotic index in
      subsets of prostate cancer: A marker reiterated in progression and recurrence of
      prostate cancer.
AB  - BACKGROUND: Prediction of biological behavior in patients of prostate cancer
      (CaP) is a major challenge as current parameters only partially meet the need for
      prognostication. p53 as a prognostic indicator has been studied in several human
      cancers, including breast, lung, and colorectal carcinoma. However, its
      significance as a predictive biomarker for CaP is less well-studied. MATERIALS
      AND METHODS: This study included 125 cases of CaP, 27 cases of prostatic
      intraepithelial neoplasia and 25 cases of benign prostatic hyperplasia.
      Immunohistochemical assessment for p53 nuclear protein was performed. Assessment
      for apoptotic index and DNA ploidy status by flow cytometry were also done.
      RESULTS: p53 immunoreactivity was low in organ confined CaP cases having Gleason
      score <=3 (P < 0.003). More hormone resistant cases 37 (83%) were aneuploid when
      compared with hormone sensitive cases 26 (33%) (P < 0.005). 93% of p53 positive
      cases and none of the p53 negative patient were aneuploid suggesting a
      significant relation between p53 immunoreactivity and aneuploidy. p53 positivity
      and DNA aneuploidy, independently, were also predictors of progression and
      relapse. CONCLUSION: DNA ploidy and p53 positivity go hand in hand and together
      yield additional prognostic information in CaP. p53 positivity is possibly a late
      event in carcinogenesis in CaP and a marker of change in biological behavior of
      CaP.

PMID- 25992351
TI  - Emerging potential of parenteral estrogen as androgen deprivation therapy for
      prostate cancer.
AB  - Androgen deprivation therapy (ADT) is a key management strategy for prostate
      cancer (PC), achieved commonly by administration of luteinizing hormone-releasing
      hormone agonist (LHRHa), ADT markedly suppresses both male and female sex
      hormones which results in "castration syndrome", a constellation of adverse
      events such as muscle weakness, impairment of glucose and lipid metabolism,
      impotence, osteoporosis, and fractures. Recent evidence suggests that estrogen,
      in the parenteral form, may emerge as an alternative to LHRHa as it offers
      potential benefits of arresting PC growth as well as avoiding some of the
      estrogen deficiency related toxicities of LHRHa by maintaining endogenous levels
      of estrogen. 

PMID- 25992350
TI  - Prognostic significance of cell surface phenotype in acute lymphoblastic
      leukemia.
AB  - CONTEXT: To find out the phenotypic character of lymphoblasts of acute
      lymphoblastic leukemia (ALL) patients in our study cohort and their possible
      effect on the prognosis. AIMS: To investigate the phenotype in ALL in our
      demographic population and to prognosticate various upfront current protocols
      employed in our hospital. SETTINGS AND DESIGN: The study spanned over a period of
      4 years with retrospective and prospective data of January 2008 through December
      2011. MATERIALS AND METHODS: 159 patients of all age groups were enrolled for the
      study, of which flow cytometry was done in 144 patients. STATISTICAL ANALYSIS
      USED: Analysis was done using the variables on SPSS (statistical package for
      social sciences) software on computer. Survival curves were estimated by method
      of Kaplan-Meir. RESULTS: Majority of the patients were of B-cell (68.1%) and
      30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa
      positivity. Complete remission (CR) was achieved in 59.1%, 16.4% relapsed, and
      20.1% patients died. CONCLUSIONS: Phenotyping has become an important and
      integral part of diagnosis, classification, management and prognosticating in
      ALL. B-cell has been found to have a better survival over T-cell lymphoblastic
      leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell
      lineage, myeloid coexpression has no significant effect on the outcome. BFM
      (Berlin-Frankfurt-Munster) based protocols though showed a higher CR and survival
      vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk
      category and lesser in numbers cannot be compared statistically with a fair
      degree of confidence.

PMID- 25992352
TI  - Midline or near-midline radioiodine uptake in the oropharyngeal region in
      patients of differentiated thyroid carcinoma: Differential diagnosis between
      lingual thyroid and retropharyngeal nodal metastasis, the subtle clues in the
      scan and their implications for patient management.

PMID- 25992353
TI  - Is female smoking rising or declining in India?

PMID- 25992354
TI  - Iatrogenic implantation of soft tissue sarcoma at skin graft donor site: Delayed
      manifestation of an avoidable complication.

PMID- 25992355
TI  - Intracranial hemorrhagic metastases as the first manifestation of an occult
      melanoma.

PMID- 25992356
TI  - Ablatio mammae like Angelina: Fad or a wise decision?

PMID- 25992357
TI  - Asynchronous cutaneous metastases of medullary thyroid carcinoma.

PMID- 25992358
TI  - Mediastinal schwannoma: A clinical, pathologic, and imaging review.

PMID- 25992359
TI  - Breast cancer in ethnically different populations.

PMID- 25992360
TI  - Gene therapy in myotubular myopathy: promising progress and future directions.

PMID- 25992361
TI  - The coming of age of adoptive T-cell therapy for viral infection after stem cell
      transplantation.

PMID- 25992362
TI  - Is there a rationale to use highly cross-linked polyethylene in posterior
      stabilized total knee arthroplasty?

PMID- 25992363
TI  - The sterile and tolerogenic fetal niche does not restrict the generation of CD4 T
      memory cells.
AB  - T-cell activation requires a sequence of signals derived from co-stimulatory
      receptors and from immunogens that may or may not be of infectious origin. This
      scenario provides the threshold of inflammatory stimulus needed for the induction
      of antigen-specific T cell responses. One of the dogmas of immunology stipulates
      that the activation of T lymphocytes is prevented in immunosuppressed or
      tolerogenic environments. However, it was shown recently that a healthy uterine
      environment that is considered sterile, therefore not exposed to infection, is
      capable of generating T memory cells with the capacity to differentiate lineage
      specific inflammatory effector T-cell responses. The implications of this finding
      are discussed in this editorial. 

PMID- 25992364
TI  - T cell activation in utero: self or non-self discrimination.

PMID- 25992365
TI  - Mitochondrial dysfunction in Kennedy's disease: a new pharmacological target?
AB  - BACKGROUND: Mitochondrial impairment and elevated oxidative stress have been
      implicated in the pathogenesis of Kennedy's disease. However, there is still no
      study describing the mitochondrial nutrient management in patients with Kennedy's
      disease. METHODS: We assessed the clinical and electrophysiological features in a
      patient with Kennedy's disease. This patient was diagnosed by genetic analysis.
      We also measured the plasma 8-hydroxydeoxyguanosine (8-OHdG) levels of the
      patient and his family members using commercial enzyme-linked immunosorbent assay
      (ELISA). Treatment with intravenous L-carnitine (2 g/day) for the patient was
      started on admission, followed by two weeks. RESULTS: Routine laboratory tests
      revealed a severe elevation of creatine kinase (CK) (606.5 U/L; normal value: 15
      170 U/L). Sequencing of the first exon of androgen receptor (AR) revealed an
      increased number of CAG repeat (50; the normal range from 10-36) in the patient.
      Plasma 8-OHdG level in the patient was relatively elevated (34.68+/-1.01 ng/mL)
      compared with the female carriers and non-carriers. Two weeks after L-carnitine
      treatment, we observed a reduction of approximately 40% in CK level (391 U/L) in
      the patient. CONCLUSIONS: Oxidative stress resulting from mitochondrial
      dysfunction could be involved in Kennedy's disease. Targeting the mitochondrial
      dysfunction in Kennedy's disease may have significant therapeutic potential.

PMID- 25992366
TI  - Lung cancer detection with digital chest tomosynthesis: first round results from
      the SOS observational study.
AB  - OBJECTIVE: Baseline results of the Studio OSservazionale (SOS), observational
      study, a single-arm observational study of digital chest tomosynthesis for lung
      cancer detection in an at-risk population demonstrated a detection rate of lung
      cancer comparable to that of studies that used low dose CT scan (LDCT). We
      present the results of the first round. METHODS: Totally 1,703 out of 1,843 (92%)
      subjects who had a baseline digital chest tomosynthesis underwent a first round
      reevaluation after 1 year. RESULTS: At first round chest digital tomosynthesis,
      13 (0.7%) subjects had an indeterminate nodule larger than 5 mm and underwent low
      dose CT scan for nodule confirmation. PET/CT study was obtained in 10 (0.5%)
      subjects and 2 subjects had a low-dose CT follow up. Surgery, either video
      assisted thoracoscopic or open surgery for indeterminate pulmonary nodules was
      performed in 10 (0.2%) subjects. A lung cancer was diagnosed and resected in five
      patients. The lung cancer detection rate at first round was 0.3% (5/1,703).
      CONCLUSIONS: The detection rate of lung cancer at first round for tomosynthesis
      is comparable to rates reported for CT. In addition, results of first round
      digital chest tomosynthesis confirm chest tomosynthesis as a possible first-line
      lung cancer-screening tool.

PMID- 25992367
TI  - MicroRNA and MET in lung cancer.
AB  - MicroRNAs (miRNAs) are a class of small non-protein coding RNAs that modulate
      important cellular functions via their post-transcriptional regulation of
      messenger RNAs (mRNAs). Recent evidences from multiple tumor types and model
      systems implicate miRNA dysregulation as a common mechanism of tumorigenesis,
      cancer progression and resistance to therapy. Several miRNAs are dysregulated in
      cancers and a single miRNA can have multiple targets involved in different
      oncogenic pathways. MET, the tyrosine kinase receptor for hepatocyte growth
      factor (HGF), has a central role in lung cancer development and in acquired
      resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors;
      it has been predicted and shown to be the target gene of multiple miRNAs, which
      play a crucial role in controlling its activity in a stimulatory or inhibitory
      sense. In this review we will focus on the most important and recent studies
      about the role of miRNAs in the control of MET expression, reporting also the
      progress made using miRNAs for therapy of lung cancer. 

PMID- 25992368
TI  - The evolution of image-guided lumbosacral spine surgery.
AB  - Techniques and approaches of spinal fusion have considerably evolved since their
      first description in the early 1900s. The incorporation of pedicle screw
      constructs into lumbosacral spine surgery is among the most significant advances
      in the field, offering immediate stability and decreased rates of pseudarthrosis
      compared to previously described methods. However, early studies describing
      pedicle screw fixation and numerous studies thereafter have demonstrated
      clinically significant sequelae of inaccurate surgical fusion hardware placement.
      A number of image guidance systems have been developed to reduce morbidity from
      hardware malposition in increasingly complex spine surgeries. Advanced image
      guidance systems such as intraoperative stereotaxis improve the accuracy of
      pedicle screw placement using a variety of surgical approaches, however their
      clinical indications and clinical impact remain debated. Beginning with
      intraoperative fluoroscopy, this article describes the evolution of image guided
      lumbosacral spinal fusion, emphasizing two-dimensional (2D) and three-dimensional
      (3D) navigational methods. 

PMID- 25992370
TI  - Anesthesia of robotic thoracic surgery.

PMID- 25992369
TI  - Body fluid biomarkers in Alzheimer's disease.
AB  - A heterogeneous and slowly progressive disease with extracellular amyloid-beta
      (Abeta) deposits and intracellular hyperphosphorylated tau protein aggregates,
      Alzheimer's disease (AD) is already a hard nut to crack, featured with cognitive
      decline and memory lapse. Body fluid biomarkers are proved to be useful in
      exploring further study of AD, might benefit for a full comprehension of the
      etiopathogenesis, an improved precision of the prognosis and diagnosis, and a
      positive response of treatments. The cerebrospinal fluid biomarkers Abeta, total
      tau, and hyperphosphorylated tau reflect the main pathologic changes of AD. We
      also review data from several novel biomarkers, such as, beta-site APP cleaving
      enzyme 1, soluble amyloid precursor proteins alpha and beta, soluble Abeta
      oligomers and so on, which are associated with the occurrence and deterioration
      of this disease and couldn't be ignored. The rationale for the clinical use of
      those biomarkers, the challenges faced with and the properties of the most
      appropriate biomarkers are also summarized in the paper. We aim to find several
      ideal biomarkers to improve the diagnosis and optimize the treatment
      respectively. 

PMID- 25992371
TI  - Diabetes management before and after cancer diagnosis: missed opportunity.
AB  - BACKGROUND: Few studies have examined the management of comorbidities in cancer
      patients. This study used population-based data to estimate the guideline
      concordance rates for diabetes management before and after cancer diagnosis and
      examined if diabetes management services among cancer patients was associated
      with characteristics of the hospital where the patient was treated. METHODS: We
      linked 2005-2009 Medicare claims data to information on 2,707 breast and
      colorectal cancers patients in state cancer registry files. Multivariate logistic
      regression models examined hospital characteristics associated with receipt of
      diabetes management care after cancer diagnosis. RESULTS: The rates of HbAlc
      testing, LDL-C testing, and retinal eye exam decreased from 72.7%, 79.6%, and
      57.9% before cancer diagnosis to 58.3%, 69.5%, and 55.8% after diagnosis. The pre
      and post-diagnosis diabetes management care was not significantly different by
      hospital characteristics in the bivariate analysis except for that the distance
      between residence and hospital was negatively related to retinal eye exam after
      diagnosis (P<0.05). The multivariate analysis did not identify any significant
      differences in diabetes management care after cancer diagnosis by hospital
      characteristics. CONCLUSIONS: Cancer patients received fewer diabetes management
      care after diagnosis than prior to diagnosis, even for those who were treated in
      large comprehensive centers. This may reflect a missed opportunity to connect
      diabetic cancer patients to diabetes care. This study provides benchmarks to
      measure improvements in comorbidity management among cancer patients.

PMID- 25992372
TI  - Primary hepatic leiomyoma: unusual cause of an intrahepatic mass.
AB  - Leiomyomas are benign lesions arising from the smooth muscle layer. They are most
      commonly detected either within the gastrointestinal or genitourinary tracts.
      Primary hepatic leiomyoma (PHL) is a rare pathology. It is an isolated pathology
      within the liver, without evidence of any other coexisting leiomyomas. Very few
      cases have been described in literature. PHL may occur in healthy individuals
      although an association with immunodeficiency and Epstein-Barr virus (EBV)
      infection has been observed. Majority of the reported cases have been in females.
      A 20-year-old female patient presented with abdominal symptoms. MRI confirmed an
      8 cm mass, with very low signal intensity on T2 images and peripheral rim
      enhancement on gadolinium. A laparoscopic left lateral sectorectomy was
      performed. Final histopathology confirmed the presence of benign lesion with
      spindle cell and smooth muscle proliferation and a fibro-vascular stroma
      compatible with a leiomyoma. There was no evidence of any leiomyomatous lesion
      elsewhere in the body. A rare diagnosis of PHL was therefore established.
      Acknowledging the rare incidence of this lesion, we report the same and review
      the relevant literature. PHL is usually a retrospective diagnosis, confirmed on
      histo-pathology assessment of the resected specimen. Liver resection is required
      in these patients due to the presence of symptoms, in the presence of a solid
      mass lesion within the liver. Surgery is thus definitive, diagnostic cum
      therapeutic. 

PMID- 25992373
TI  - Physical attraction of Th9 cells is skin deep.

PMID- 25992374
TI  - Interaction non grata between CFTR's correctors and potentiators.

PMID- 25992375
TI  - A specific molecular signature for psoriasis and eczema.
AB  - Psoriasis and eczema seem to present a specific distinctive gene expression
      pattern. In the Science Translation Medicine (Sci Transl Med), Quaranta et al.
      reported a specific molecular signature of psoriasis and eczema. By using an
      intraindividual genome expression analysis in patients affected by both diseases,
      the authors identified genes and signaling pathways that are regulated in common
      and that are exclusive for each disease. 

PMID- 25992376
TI  - Tranexamic acid and orthopedic surgery-the search for the holy grail of blood
      conservation.

PMID- 25992377
TI  - Elucidating new drug targets in psoriasis by gene profiling: an opportunity to be
      seized.

PMID- 25992378
TI  - High fat diet-induced obesity increases the formation of colon polyps induced by
      azoxymethane in mice.
AB  - BACKGROUND: Obesity has been found to be associated with colon cancer. However,
      the mechanism of this relationship is unclear and thus a good animal model is
      required. Our previous research showed that some mice developed diet-induced
      obesity (DIO) whilst others were diet-resistant (DR) when fed a high-fat diet.
      METHODS: In the present study, we have tested the effects of a high-fat diet on
      the formation of colon polyps induced by azoxymethane (AOM) in both DIO and DR
      mice. RESULTS: We found that the DIO mice have developed 2.5 times of polyps
      compared to the DR mice (P<0.05) and 3.4 times of polyps compared to the low fat
      fed mice (P<0.05). Although the DR mice tended to have more polyps than the low
      fat diet fed mice, this was not statistically significant. The DIO mice could
      have an increased polyp formation due to obesity-related cancer risk factors and
      different gene expression from DR mice. CONCLUSIONS: DIO mice could be used as an
      appropriate model for studying obesity-associated colon cancer; however DR mice
      are not suitable because they don't show any significant weight gains to indicate
      obesity.

PMID- 25992379
TI  - Hyaluronan expression in primary and secondary brain tumors.
AB  - BACKGROUND: Collectively, primary and secondary brain tumors represent a major
      public health challenge. Glioblastoma (GBM) is the most common primary brain
      tumor in adults and is associated with a dismal 5-year survival of only 10%.
      Breast cancer causes secondary tumors; it occurs in 200,000 patients yearly and
      30% of these individuals develop brain metastases which also lead to a very poor
      prognosis. GBM and primary breast tumors are known to express hyaluronan (HA)
      which may serve as a therapeutic target. METHODS: For the present study we had
      two aims: (I) to identify suitable preclinical models for HA in GBM by examining
      HA expression in human GBM cell lines implanted orthotopically in mice; and (II)
      to determine whether breast cancer brain metastases in human patients express HA
      similar to the primary tumor. Forty human surgical samples of primary breast
      tumors and breast cancer brain metastases were processed and stained for HA.
      Athymic nu/nu mice were orthotopically implanted with one of 15 GBM lines and
      after tumors were established, quantitative immunohistochemistry determined
      whether. RESULTS: HA was expressed. All GBM cell lines and patient-derived
      orthotopic tumors did express HA, with 3 primary human lines expressing the
      highest staining intensity, above that of normal brain. All 40 human primary
      breast tumors and brain metastases examined also contained HA, though staining
      intensity was highly variable. CONCLUSIONS: Our data support the use of specific
      patient-derived GBM cell lines in nu/nu mice for preclinical studies on HA
      targeting therapies. Additionally, our research provides a basis for the
      assessment of HA expression and HA-targeting therapeutic agents for the treatment
      of breast cancer brain metastases.

PMID- 25992380
TI  - Role of mesenchymal-epithelial transition amplification in resistance to anti
      epidermal growth factor receptor agents.
AB  - All patients with epidermal growth factor receptor (EGFR) mutant advanced non
      small cell lung cancer (NSCLC) treated with an EGFR-tyrosine kinase inhibitor
      (EGFR-TKI) such as gefitinib, erlotinib or afatinib will progress after a median
      of 9-12 months. So far, development of a secondary T790M mutation represents the
      most common (approximately 60%) mechanism of resistance to these drugs. The
      relative rarity of mesenchymal-epithelial transition (MET) amplification in NSCLC
      suggests that this event plays a limited role in primary resistance to EGFR-TKI.
      In contrast, MET gene amplification has been detected as a secondary event
      representing one of the most relevant mechanisms involved in the acquired
      resistance to EGFR-TKIs both in preclinical and clinical studies. The aim of this
      review is to discuss the role of MET amplification as a mechanism of resistance
      to anti-EGFR therapies and to review strategies which aim at overcoming this
      mechanism of resistance, including studies assessing drug combinations targeting
      both EGFR and MET pathways. 

PMID- 25992383
TI  - Technical highlights of robotic-assisted mediastinal tumor resection.

PMID- 25992382
TI  - Prognostic and predictive value of MET deregulation in non-small cell lung
      cancer.
AB  - Recent progress in cancer biology has led to the discovery of increasing number
      of oncogene alterations that have dramatically changed the paradigm of lung
      cancer treatment. MET is a tyrosine kinase receptor for the hepatocyte growth
      factor (HGF) that is deregulated in several malignancies, including non-small
      cell lung cancer (NSCLC). Abnormal MET-HGF signaling pathway activation can occur
      via different mechanisms, including HGF and/or MET overexpression, MET gene
      amplification, mutations or rearrangements. MET protein overexpression and
      increased MET gene number have been identified as poor prognostic factors in
      several series of surgically resected NSCLC making this receptor an attractive
      target for cancer treatment. Several clinical trials have recently evaluated the
      activity of a variety of anti-MET strategies in NSCLC patients with or without
      molecular selection with a variable degree of success, underscoring the need of
      establishing the best predictive biomarker for the identification of responding
      patients. 

PMID- 25992384
TI  - The real difficulty in improving concordance of clinical practice with
      guidelines.

PMID- 25992381
TI  - Biology of MET: a double life between normal tissue repair and tumor progression.
AB  - MNNG HOS transforming gene (MET) is a class IV receptor tyrosine kinase,
      expressed on the surface of epithelial cells. The interaction with the hepatocyte
      grow factor (HGF) induces MET dimerization and the activation of multiple
      intracellular pathways leading to cell proliferation, anti-apoptosis, morphogenic
      differentiation, motility, invasion, and angiogenesis. Knock out mice have
      demonstrated that MET is necessary for normal embryogenesis including the
      formation of striate muscles, liver and trophoblastic structures. The
      overexpression of MET and HGF are common in solid tumors and contribute to
      determine their growth. Indeed, MET has been cloned as a transforming gene from a
      chemically induced human osteosarcoma cell line and therefore is considered a
      proto-oncogene. Germline MET mutations are characteristic of hereditary papillary
      kidney cancers and MET amplification is observed in tumors including lung and
      gastric adenocarcinomas. The inhibition of MET signaling is the target for
      specific drugs that are raising exciting expectation for medical treatment of
      cancer. 

PMID- 25992385
TI  - Transparent reporting of data quality in distributed data networks.
AB  - INTRODUCTION: Poor data quality can be a serious threat to the validity and
      generalizability of clinical research findings. The growing availability of
      electronic administrative and clinical data is accompanied by a growing concern
      about the quality of these data for observational research and other analytic
      purposes. Currently, there are no widely accepted guidelines for reporting
      quality results that would enable investigators and consumers to independently
      determine if a data source is fit for use to support analytic inferences and
      reliable evidence generation. MODEL AND METHODS: We developed a conceptual model
      that captures the flow of data from data originator across successive data
      stewards and finally to the data consumer. This "data lifecycle" model
      illustrates how data quality issues can result in data being returned back to
      previous data custodians. We highlight the potential risks of poor data quality
      on clinical practice and research results. Because of the need to ensure
      transparent reporting of a data quality issues, we created a unifying data
      quality reporting framework and a complementary set of 20 data-quality reporting
      recommendations for studies that use observational clinical and administrative
      data for secondary data analysis. We obtained stakeholder input on the perceived
      value of each recommendation by soliciting public comments via two face-to-face
      meetings of informatics and comparative-effectiveness investigators, through
      multiple public webinars targeted to the health services research community, and
      with an open access online wiki. RECOMMENDATIONS: Our recommendations propose
      reporting on both general and analysis-specific data quality features. The goals
      of these recommendations are to improve the reporting of data quality measures
      for studies that use observational clinical and administrative data, to ensure
      transparency and consistency in computing data quality measures, and to
      facilitate best practices and trust in the new clinical discoveries based on
      secondary use of observational data.

PMID- 25992386
TI  - Assessing the potential adoption and usefulness of concurrent, action-oriented,
      electronic adverse drug event triggers designed for the outpatient setting.
AB  - BACKGROUND: Adverse drug event (ADE) detection is an important priority for
      patient safety research. Trigger tools have been developed to help identify ADEs.
      In previous work we developed seven concurrent, action-oriented, electronic
      trigger algorithms designed to prompt clinicians to address ADEs in outpatient
      care. OBJECTIVES: We assessed the potential adoption and usefulness of the seven
      triggers by testing the positive predictive validity and obtaining stakeholder
      input. METHODS: We adapted ADE triggers, "bone marrow toxin-white blood cell
      count (BMT-WBC)," "bone marrow toxin - platelet (BMT-platelet)," "potassium
      raisers," "potassium reducers," "creatinine," "warfarin," and "sedative
      hypnotics," with logic to suppress flagging events with evidence of clinical
      intervention and applied the triggers to 50,145 patients from three large health
      care systems. Four pharmacists assessed trigger positive predictive value (PPV)
      with respect to ADE detection (conservatively excluding ADEs occurring during
      clinically appropriate care) and clinical usefulness (i.e., whether the trigger
      alert could change care to prevent harm). We measured agreement between raters
      using the free kappa and assessed positive PPV for the trigger's detection of
      harm, clinical usefulness, and both. Stakeholders from the participating health
      care systems rated the likelihood of trigger adoption and the perceived ease of
      implementation. FINDINGS: Agreement between pharmacist raters was moderately high
      for each ADE trigger (kappa free > 0.60). Trigger PPVs for harm ranged from 0
      (Creatinine, BMT-WBC) to 17 percent (potassium raisers), while PPV for care
      change ranged from 0 (WBC) to 60 percent (Creatinine). Fifteen stakeholders rated
      the triggers. Our assessment identified five of the seven triggers as good
      candidates for implementation: Creatinine, BMT-Platelet, Potassium Raisers,
      Potassium Reducers, and Warfarin. CONCLUSIONS: At least five outpatient ADE
      triggers performed well and merit further evaluation in outpatient clinical care.
      When used in real time, these triggers may promote care changes to ameliorate
      patient harm.

PMID- 25992387
TI  - Development and applications of an outcomes assessment framework for care
      management programs in learning health systems.
AB  - PURPOSE: To develop and apply an outcomes assessment framework (OAF) for care
      management programs in health care delivery settings. BACKGROUND: Care management
      (CM) refers to a regimen of organized activities that are designed to promote
      health in a population with particular chronic conditions or risk profiles, with
      focus on the triple aim for populations: improving the quality of care, advancing
      health outcomes, and lowering health care costs. CM has become an integral part
      of a care continuum for population-based health care management. To sustain a CM
      program, it is essential to assure and improve CM effectiveness through rigorous
      outcomes assessment. To this end, we constructed the OAF as the foundation of a
      systematic approach to CM outcomes assessment. INNOVATIONS: To construct the OAF,
      we first systematically analyzed the operation process of a CM program; then,
      based on the operation analysis, we identified causal relationships between
      interventions and outcomes at various implementation stages of the program. This
      set of causal relationships established a roadmap for the rest of the outcomes
      assessment. Built upon knowledge from multiple disciplines, we (1) formalized a
      systematic approach to CM outcomes assessment, and (2) integrated proven
      analytics methodologies and industrial best practices into operation-oriented CM
      outcomes assessment. CONCLUSION: This systematic approach to OAF for assessing
      the outcomes of CM programs offers an opportunity to advance evidence-based care
      management. In addition, formalized CM outcomes assessment methodologies will
      enable us to compare CM effectiveness across health delivery settings.

PMID- 25992388
TI  - Operationalizing the learning health care system in an integrated delivery
      system.
AB  - INTRODUCTION: The Learning Health Care System (LHCS) model seeks to utilize
      sophisticated technologies and competencies to integrate clinical operations,
      research and patient participation in order to continuously generate knowledge,
      improve care, and deliver value. Transitioning from concept to practical
      application of an LHCS presents many challenges but can yield opportunities for
      continuous improvement. There is limited literature and practical experience
      available in operationalizing the LHCS in the context of an integrated health
      system. At Geisinger Health System (GHS) a multi-stakeholder group is undertaking
      to enhance organizational learning and develop a plan for operationalizing the
      LHCS system-wide. We present a framework for operationalizing continuous learning
      across an integrated delivery system and lessons learned through the ongoing
      planning process. FRAMEWORK: The framework focuses attention on nine key LHCS
      operational components: Data and Analytics; People and Partnerships; Patient and
      Family Engagement; Ethics and Oversight; Evaluation and Methodology; Funding;
      Organization; Prioritization; and Deliverables. Definitions, key elements and
      examples for each are presented. The framework is purposefully broad for
      application across different organizational contexts. CONCLUSION: A realistic
      assessment of the culture, resources and capabilities of the organization related
      to learning is critical to defining the scope of operationalization. Engaging
      patients in clinical care and discovery, including quality improvement and
      comparative effectiveness research, requires a defensible ethical framework that
      undergirds a system of strong but flexible oversight. Leadership support is
      imperative for advancement of the LHCS model. Findings from our ongoing work
      within the proposed framework may inform other organizations considering a
      transition to an LHCS.

PMID- 25992389
TI  - Linking electronic health records to better understand breast cancer patient
      pathways within and between two health systems.
AB  - INTRODUCTION: In a fragmented health care system, research can be challenging
      when one seeks to follow cancer patients as they seek care which can continue for
      months or years and may reflect many physician and patient decisions. Claims data
      track patients, but lack clinical detail. Linking routine electronic health
      record (EHR) data with clinical registry data allows one to gain a more complete
      picture of the patient journey through a cancer care episode. However, valid
      analytical approaches to examining care trajectories must be longitudinal and
      account for the dynamic nature of what is "seen" in the EHR. METHODS: The
      Oncoshare database combines clinical detail from the California Cancer Registry
      and EHR data from two large health care organizations in the same catchment area
      a multisite community practice and an academic medical center-for all women
      treated in either organization for breast cancer from 2000 to 2012. We classified
      EHR encounters data according to typical periods of the cancer care episode
      (screening, diagnosis, treatment) and posttreatment surveillance, as well as by
      facility used to better characterize patterns of care for patients seen at both
      organizations. FINDINGS: We identified a "treated" cohort consisting of women
      receiving interventions for their initial cancer diagnosis, and classified their
      encounters over time across multiple dimensions (type of care, provider of care,
      and timing of care with respect to their cancer diagnosis). Forty-three percent
      of the patients were treated at the academic center only, 42 percent at the
      community center only, and 16 percent of the patients obtained care at both
      health care organizations. Compared to women seen at only one organization, the
      last group had similar-length initial care episodes, but more frequently had
      multiple episodes and longer observation periods. DISCUSSION: Linking EHR data
      from neighboring systems can enhance our information on care trajectories, but
      careful consideration of the complexity of the treatment process and data
      generating mechanisms is necessary to make valid inferences. CONCLUSION/NEXT
      STEPS: If analyzed as a timeline, and with careful characterization of diagnostic
      tests, surgical interventions, and type and frequency of physician encounters,
      the pathways taken by women through their breast cancer episode may lead to
      better understanding of patient decisions.

PMID- 25992390
TI  - Patients, consumers, and caregivers: the original data stewards.
AB  - INTRODUCTION: For patients and families, the issue of data quality is personal.
      When treatment decisions or research conclusions are based on incomplete or
      inaccurate information-a misdiagnosis, an incomplete medication list, the wrong
      demographic data-care safety, quality, and outcomes suffer-and patients and
      families suffer. OPPORTUNITY FOR CHANGE: Thanks in part to the power of health
      information technology, individuals have new opportunities to be part of the
      solution when it comes to assessing and improving data quality. Building on a
      framework for data quality, there are numerous opportunities for patients to be
      part of 'feedback loops' to understand and improve data quality are presented.
      FOUNDATION FOR THE FUTURE: As the source of patient-centered data, consumers have
      important roles to play in reviewing and confirming their own health information
      and should be engaged partners in efforts to understand and improve the quality
      of electronic health data.

PMID- 25992391
TI  - Development of the Lesbian, Gay, and Bisexual Affirmative Counseling Self
      Efficacy Inventory - Short Form (LGB-CSI-SF).
AB  - The Lesbian, Gay, and Bisexual Affirmative Counseling Self-Efficacy Inventory -
      Short Form (LGB-CSI-SF) was developed to facilitate LGB-affirmative counseling
      training, as well as process and outcome research, by offering a brief
      psychometrically supported version of the original LGB-CSI measure to researchers
      and clinicians. Five hundred seventy-five participants (435 licensed mental
      health professionals and 140 graduate students/trainees) constituted the sample.
      Confirmatory factor analyses of the 32 items from the original LGB-CSI yielded a
      new 15-item version of the measure composed of 5 factors (consisting of 3 items
      each) that assess counselor self-efficacy to perform lesbian, gay, and bisexual
      (LGB) affirmative counseling behaviors (Application of Knowledge, Advocacy
      Skills, Self-Awareness, Relationship, and Assessment). The LGB-CSI-SF evidenced
      high internal consistency and adequate test-retest stability. Convergent validity
      was supported by correlations between LGB-CSI-SF total scores and Application of
      Knowledge, Advocacy Skills, Relationship, and Assessment subscales and
      instruction in LGB issues, as well as personal/professional relations with LGB
      individuals. More affirmative attitudes toward LGB persons positively related
      with total scores and Advocacy Skills, Self-Awareness, and Relationship
      subscales. Discriminant validity was evidenced by an absence of relations between
      LGB-CSI-SF subscales and a measure of impression management. We found no
      associations between Advocacy Skills, Assessment, and Relationship subscales and
      a measure of Self-Deception. Recommendations for implementing the LGB-CSI-SF in
      future LGB-affirmative counseling self-efficacy based research and training
      interventions are discussed.

PMID- 25992392
TI  - Reply: To PMID 25290788.

PMID- 25992393
TI  - Diagnosis of bacteremia on a blood smear.

PMID- 25992394
TI  - Corrigendum.
AB  - In the following article--Calvo, G., Holden, E., Reid, J., Scott, E. M., Firth,
      A., Bell, A., Robertson, S. and Nolan A. M. (2014) Development of a behaviour
      based measurement tool with defined intervention level for assessing acute pain
      in cats. Journal of Small Animal Practice, 55, 622-629-- the copyright
      information for Appendix 2 was placed incorrectly under Appendix 1.The copyright
      information for Appendix 2 is: Copyright (c) 2010 University of Glasgow.
      Permission granted to reproduce for personal and educational use only.Commercial
      copying, hiring, lending is prohibited. The authors wish to notify the readership
      of this error.

PMID- 25992395
TI  - [Is it still necessary to screen for asymptomatic bacteriuria among patients
      undergoing joint prosthesis insertion?].

PMID- 25992396
TI  - [Vaccines and central nervous system demyelinating diseases: New studies on the
      internet -not just new rumors].

PMID- 25992397
TI  - [Is a vancomycin MIC >= 1.5 mg/L associated with a worse prognosis in patients
      with S. aureus bloodstream infection?].

PMID- 25992398
TI  - The gastric residual question.

PMID- 25992399
TI  - Comment on: "Prevalence of diabetes in people aged >30 years: the results of
      screening program of Yazd province, Iran in 2012". Reply.

PMID- 25992400
TI  - Right brain: the e-lephant in the room: one resident's challenge in transitioning
      to modern electronic medicine.

PMID- 25992401
TI  - Naltrexone for impulse control disorders in Parkinson disease: a placebo
      controlled study.

PMID- 25992402
TI  - Naltrexone for impulse control disorders in Parkinson disease: a placebo
      controlled study.

PMID- 25992403
TI  - Re: Rodrigues JN, Zhang W, Scammell BE, Davis TRC. What patients want from the
      treatment of Dupuytren's disease - is the Unite Rhumatologique des Affections de
      la Main (URAM) scale relevant? J Hand Surg Eur. Epub ahead of print 21 February
      2014. DOI: 10.1177/1753193414524689.

PMID- 25992404
TI  - A special issue on reviews in biomedical applications of nanomaterials, tissue
      engineering, stem cells, bioimaging, and toxicity.
AB  - This second special issue of the Journal of Biomedical Nanotechnology in a series
      contains another 30 state-of-the-art reviews focused on the biomedical
      applications of nanomaterials, biosensors, bone tissue engineering, MRI and
      bioimaging, single-cell detection, stem cells, endothelial progenitor cells,
      toxicity and biosafety of nanodrugs, nanoparticle-based new therapeutic
      approaches for cancer, hepatic and cardiovascular disease.

PMID- 25992405
TI  - Endovascular stents and stent grafts in the treatment of cardiovascular disease.
AB  - Endovascular stents and stent grafts are increasingly used to treat a variety of
      cardiovascular diseases and these endovascular devices have gained popularity
      worldwide. The improvement of available endovascular devices is critical for the
      advancement of patient care in cardiovascular medicine. Problems are still
      associated with the endovascular treatments, many of which can adversely affect
      the treatment outcomes, such as the conversion of the patient to conventional
      open surgery, or resulting in procedure-related complications. This review aims
      to provide an overview of the commonly performed endovascular procedures
      including carotid artery stenting, coronary artery stenting, peripheral arterial
      stenting and endovascular stent grafting with regard to clinical outcomes and
      imaging assessment. A critical appraisal is given to the novel methods that have
      been recently developed to deal with these problems and future development of the
      endovascular devices is highlighted.

PMID- 25992406
TI  - Hierarchical mechanics of connective tissues: integrating insights from nano to
      macroscopic studies.
AB  - As the key component of the musculoskeletal system, the extracellular matrix of
      soft connective tissues such as ligaments and tendons is a biological example of
      fibre-reinforced composite but with a complex hierarchical architecture. To
      establish a comprehensive structure-function relationship at the respective
      levels (i.e., from molecule to tissue) of the hierarchical architecture is
      challenging and requires a multidisciplinary approach, involving the integration
      of findings from the fields of molecular biology, biochemistry, structural
      biology, materials science and biophysics. Accordingly, in recent years, some of
      these fields, namely structural biology, materials science and biophysics, have
      made significant progress in the microscale and nanoscale studies of
      extracellular matrix using new tools, such as microelectromechanical systems,
      optical tweezers and atomic force microscopy, complemented by new techniques in
      simultaneous imaging and mechanical testing and computer modelling. The intent of
      this paper is to review the key findings on the mechanical response of
      extracellular matrix at the respective levels of the hierarchical architecture.
      The main focus is on the structure and function--the findings are compared across
      the different levels to provide insights that support the goal of establishing a
      comprehensive structure-function relationship of extracellular matrix. For this
      purpose, the review is divided into two parts. The first part explores the
      features of key structural units of extracellular matrix, namely tropocollagen
      molecule (the lowest level), microfibril, collagen fibril, collagen fibre and
      fascicle. The second part examines the mechanics of the structural units at the
      respective levels. Finally a framework for extracellular matrix mechanics is
      proposed to support the goal to establish a comprehensive structure-function
      relationship. The framework describes the integration of the mechanisms of
      reinforcement by the structural units at the respective levels of the
      hierarchical architecture in a consistent manner, both to allow comparison of
      these mechanisms, and to make prediction of the interconnection of these
      mechanisms that can also assist in the identification of effective mechanical
      pathways. From a design perspective, this is a step in the direction towards the
      development of effective strategies for engineering materials to replace or
      repair damaged tissues, and for exogenous cross-linking therapy to enhance the
      mechanical properties of injured tissues.

PMID- 25992407
TI  - Shape-mediated biological effects of mesoporous silica nanoparticles.
AB  - For biomedical applications, mesoporous silica nanoparticles (MSNs)-based
      theranostic agents have shown to be a promising alternative. Rational design of
      particulate systems should consider, beside the physicochemical properties of
      particle size and surface chemistry, shape features as aspect ratio (AR) and
      morphology. Recent advances of fabrication technologies for manufacturing
      different shaped MSNs and evaluation means of its in vitro and in vivo biological
      performance provide new aspects and wisdom in nanomedicine development. In this
      review, we discussed the recent progress in the preparation of different shaped
      MSNs and the evaluation of shape-mediated biological effects. Firstly, we provide
      an overview of preparation strategies for fabricating MSNs with different aspect
      ratios and different morphologies, including hollow/rattle MSNs, multishell MSNs,
      and mesoporous silica nanocomposites. We then highlight the aspect ratio- and
      morphology-mediated biological effects of MSNs respectively. For AR-mediated
      biological effects of MSNs, we put our focus in the particle ARs effect on
      cellular uptake, biocompatibility, and drug delivery. For morphology-mediated
      biological effects of MSNs, we emphasize on how particle shapes could affect
      tumor therapy. Finally, for application considerations, we conclude with our
      personal perspectives on the directions in which future studies in this field
      might be placed.

PMID- 25992408
TI  - Applications of carbon nanotubes in stem cell research.
AB  - Stem cells are a key element in tissue engineering and regenerative medicine.
      However, they require a suitable microenvironment to grow and regenerate. Carbon
      nanotubes (CNTs) have attracted much attention as promising materials for stem
      cell research due to their extraordinary properties, such as their extracellular
      matrix-like structure, high mechanical strength, optical properties, and high
      electrical conductivity. Of particular interest is the use of CNTs as biomimetic
      substrates to control the differentiation of stem cells. CNTs have also been
      combined with commonly used scaffolds to fabricate functional scaffolds to direct
      stem cell fate. CNTs can also be used for stem cell labeling due to their high
      optical absorbance in the near-infrared regime. In this paper, we review and
      discuss the applications of CNTs in stem cell research along with CNT toxicity
      issues.

PMID- 25992409
TI  - Modeling of human cardiomyopathy with induced pluripotent stem cells.
AB  - Human inherited cardiomyopathies are one of the major etiologies for heart
      failure which are associated with significant mortality and morbidity.
      Unfortunately, there are lack of effective specific therapies for human
      cardiomyopathies due to the limited understanding on their pathophysiology.
      Currently, most of the mechanistic studies of human cardiomyopathy are based on
      transgenic mouse models and invasive collection of limited amount of myocardial
      biopsy specimen. Disease-specific stem-cells are already available for studying
      single-gene mutation related diseases, such as cystic fibrosis and fragile X
      syndrome. The possibility of obtaining stem-cells using induced pluripotent stem
      cell (iPSC) technology provides the opportunity to generate stem cells carrying
      an inherited disease phenotype that will then serve as an invaluable model to
      study the disease biology and treatment of human cardiomyopathies. Here, we
      review the major strategies and workflow of using the patient-specific iPSCs
      derived cardiomyocytes to model inherited human cardiomyopathies. The creation of
      patient-specific iPSC lines in patients with hypertrophic cardiomyopathy and
      dilated cardiomyopathy have been reported and served as important human models of
      inherited diseases to improve our understanding of the disease mechanisms and
      enable drug screening.

PMID- 25992410
TI  - Effects of shear stress on endothelial progenitor cells.
AB  - Endothelial progenitor cells (EPCs) are adult stem cells that play a central role
      in neovascularization. EPCs are mobilized from bone marrow into peripheral blood,
      attach to existing endothelial cells, and then transmigrate across the
      endothelium into tissues, where they proliferate, differentiate, and form new
      blood vessels. In the process, EPCs are exposed to shear stress, a biomechanical
      force generated by flowing blood and tissue fluid flow. When cultured EPCs are
      exposed to controlled levels of shear stress in a flow-loading device, their
      bioactivities in terms of proliferation, anti-apoptosis, migration, production of
      bioactive substances, anti-thrombosis, and tube formation increase markedly.
      Expression of endothelial marker genes and proteins by EPCs also increases in
      response to shear stress, and they differentiate into mature endothelial cells.
      Great advances have been made in elucidating the mechanisms by which mature
      endothelial cells sense and respond to shear stress, but not in EPCs. Further
      study of EPC responses to shear stress will be necessary to better understand the
      physiological and pathophysiological roles of EPCs and to apply EPCs to new
      therapies in the field of regenerative medicine.

PMID- 25992411
TI  - The role of nanotechnology in single-cell detection: a review.
AB  - Biological processes in single cells, such as signal transduction, DNA
      duplication, and protein synthesis and trafficking, occur in subcellular
      compartments at nanoscale level. Achieving high spatial-temporal resolution, high
      sensitivity, and high specificity in single-cell detection poses a great
      challenge. Nanotechnology, which has been widely applied in the fields of
      medicine, electronics, biomaterials, and energy production, has the potential to
      provide solutions for single-cell detection. Here we present a review of the use
      of nanotechnology in single-cell detection over the past two decades. First, we
      review the main areas of scientific interest, including morphology, ion
      concentration, DNA, RNA, protein, intracellular temperature, elements, and
      mechanical properties. Second, four categories of application of nanotechnology
      to single-cell detection are described: nanomanipulation, nanodevices,
      nanomaterials as labels, and nano Secondary ion mass spectrometry. Finally, the
      prospects and future trends in single-cell detection and analysis are discussed.

PMID- 25992412
TI  - Selective fluorescence and fluorescence-free detection of single biomolecules on
      nanobiochips.
AB  - This topical review provides an overview of selective fluorescence and
      fluorescence-free detection on nanobiochips fabricated by nanopatterning
      techniques such as nanolithography and the use of artificial nanostructures
      (arrays of pillars, holes, and wires). The unique properties of nanostructured
      surfaces have led to applications in biomedical nanoarrays used for either
      diagnostic or functional assays on chips. Some targets can be optically detected
      using not only colorimetry, chemiluminescence or the most developed fluorescence
      mode, but also more recent non-conventional optical methods. Two main approaches
      have been used: fluorescence (e.g., epifluorescence and total internal
      reflection) and fluorescence-free (e.g., surface plasmon resonance, optical
      resonance, dark-field scattering, atom force microscopy, electrochemical method,
      etc.) detection. The aim of the present paper is to review the most recent
      progress in nanobiochips in the development of new selective fluorescence and
      fluorescence-free detection at the single-molecule level.

PMID- 25992413
TI  - Nanoparticles for molecular imaging.
AB  - Imaging techniques have been instrumental in the visualization of fundamental
      biological processes, identification and diagnosis of diseased states and the
      development of structure-function relationships at the cellular, tissue and
      anatomical levels. Together with the advancements made in imaging techniques,
      complementary chemical compounds, also known as imaging probes or contrast
      agents, are developed to improve the visibility of the image by enhancing
      sensitivity, and for the identification and quantitation of specific molecular
      species or structures. Extensive studies have been conducted to explore the use
      of inorganic nanoparticles which exhibit magnetic and optical properties unique
      to the nano regime so as to enhance the signals sensitivity for magnetic
      resonance and fluorescent imaging. These physical properties are tailored by
      controlling the size, shape and surface properties of nanoparticles. In addition,
      surface modification of nanoparticles is often required to improve its stability,
      compatibility and functionality. Surfactants, surface-active agents, have been
      used to engineer the surface characteristics of nanoparticles to improved
      particle stability and functionality. Surfactants enhance nanoparticle stability
      through the reduction of surface energy, and by acting as a barrier to
      agglomeration through either steric hindrance or repulsive electrostatic forces.
      Coupling of nanoparticles with biomolecules such as antibodies or tumor targeting
      peptides are enabled by the presence of functional groups (e.g., carboxyl or
      amine groups) on surfactants. This paper provides an overview of the chemistry
      underlying the synthesis and surface modification of nanomaterials together with
      a discussion on how the physical properties (e.g., magnetic, absorption and
      luminescent) can be controlled. The applications of these nanoparticles for
      magnetic resonance, fluorescent and photoacoustic imaging techniques that do not
      rely on ionizing radiation are also covered in this review.

PMID- 25992414
TI  - Fluorescent carbon dots for biolmaging and biosensing applications.
AB  - Due to the excellent biocompatibility, carbon dots (CDs), which are attracting
      considerable attention as new quantum-sized carbon-containing fluorescent
      nanoparticles, are becoming both an important class of imaging probes and a
      versatile platform for biosensors. In the process of transferring carbon dots
      from proof-of-concept studies to real bioimaging and biosensing applications,
      major advances have already been made in their synthesis, structure, properties,
      mechanism of fluorescence, and evaluation of biocompatibility and bio
      applications. This review aims to summarize the recent developments and trends in
      carbon dots. Investigations of preparation methods, fluorescent properties and
      applications as biosensors and in bioimaging for carbon dots are described. In
      addition, this review highlights on the design and construct of a carbon dot
      fluorescent ratiometric biosensing platform for the detection of enzymatic
      activity, substrate and inhibitor concentrations related to the production or
      consumption of H2O2. This review provides perspectives on future opportunities
      and the remaining challenges confronting this research field.

PMID- 25992415
TI  - Applications of gold nanoparticles in optical biosensors.
AB  - Currently gold nanoparticles are widely used in optical bioassays because of
      their characteristics, such as good biocompatibility, excellent optical
      performance, special catalytic activity and the convenience of controlled
      fabrication. This review describes the application development of gold
      nanoparticles in various optical biosensors, including colorimetry, scanometry,
      dry-reagent strip, surface plasmon resonance (SPR), surface-enhanced Raman
      scattering (SERS), chemiluminescence and fluorescent biosensors. Firstly, we
      present the underlying principles that contribute to the enhanced detection
      capability of gold nanoparticles, taking advantage of their unique
      characteristics in these bioassay methods. We then demonstrate selected examples
      to illustrate the development of each method, focusing on the performance
      improvement of the biosensor, such as sensitivity, selectivity and so on.
      Finally, we conclude and discuss the future prospects of using gold nanoparticles
      in biosensors.

PMID- 25992416
TI  - Nanosensors for regenerative medicine.
AB  - Assessing biodistribution, fate, and function of implanted therapeutic cells in
      preclinical animal experiments is critical to realize safe, effective and
      efficient treatments for subsequent implementation within the clinic. Currently,
      tissue histology, the most prevalent analytical technique to meet this need, is
      limited by end-point analysis, high cost and long preparation time. Moreover, it
      is disadvantaged by an inability to monitor in real-time, qualitative
      interpretation and ethical issues arising from animal sacrifice. While genetic
      engineering techniques allow cells to express molecules with detectable signals
      (e.g., fluorescence, luminescence, T1 (spin-lattice)/T2 (spin-spin) contrast in
      magnetic resonance imaging, radionuclide), concerns arise regarding technical
      complexity, high-cost of genetic manipulation, as well as mutagenic cell
      dysfunction. Alternatively, cells can be labeled using nanoparticle-sensors
      nanosensors that emit signals to identify cell location, status and function in a
      simple, cost-effective, and non-genetic manner. This review article provides the
      definition, classification, evolution, and applications of nanosensor technology
      and focuses on how they can be utilized in regenerative medicine. Several
      examples of direct applications include: (1) monitoring post-transplantation cell
      behavior, (2) revealing host response following foreign biomaterial implantation,
      and (3) optimization of cell bioprocess operating conditions. Incorporating
      nanosensors is expected to expedite the development of cell-based regenerative
      medicine therapeutics.

PMID- 25992417
TI  - In-vitro and in-vivo diagnostic techniques for prostate cancer: a review.
AB  - This paper overviews one of the most important, interesting, and challenging
      problems in oncology, early diagnosis of prostate cancer. Developing effective
      diagnostic techniques for prostate cancer is of great clinical importance and can
      improve the effectiveness of treatment and increase the patient's chance of
      survival. The main focus of this study is to overview the different in-vitro and
      in-vivo technologies for diagnosing prostate cancer. This review discusses the
      current clinically used in-vitro cancer diagnostic tools, such as biomarker tests
      and needle biopsies and including their applications, advantages, and
      limitations. Moreover, the current in-vitro research tools that focus on the role
      of nanotechnology in prostate cancer diagnosis have been detailed. In addition to
      the in-vitro techniques, the current study discusses in detail developed in-vivo
      non-invasive state-of-the-art Computer-Aided Diagnosis (CAD) systems for prostate
      cancer based on analyzing Transrectal Ultrasound (TRUS) and different types of
      magnetic resonance imaging (MRI), e.g., T2-MRI, Diffusion Weighted Imaging (DWI),
      Dynamic Contrast Enhanced (DCE)-MRI, and multi-parametric MRI, focusing on their
      implementation, experimental procedures, and reported outcomes. Furthermore, the
      paper addresses the limitations of the current prostate cancer diagnostic
      techniques, outlines the challenges that these techniques face, and introduces
      the recent trends to solve these challenges, which include biomarkers used in in
      vitro lab-on-a-chip nanotechnology-based methods.

PMID- 25992418
TI  - Magnetic resonance imaging findings for dyslexia: a review.
AB  - Developmental dyslexia is a brain disorder that is associated with a disability
      to read, which affects both the behavior and the learning abilities of children.
      Recent advances in MRI techniques have enabled imaging of different brain
      structures and correlating the results to clinical findings. The goal of this
      paper is to cover these imaging studies in order to provide a better
      understanding of dyslexia and its associated brain abnormalities. In addition,
      this survey covers the noninvasive MRI-based diagnostics methods that can offer
      early detection of dyslexia. We focus on three MRI techniques: structural MRI,
      functional MRI, and diffusion tensor imaging. Structural MRI reveals dyslexia
      associated volumetric and shape-based abnormalities in different brain structures
      (e.g., reduced grey matter volumes, decreased cerebral white matter
      gyrifications, increased corpus callosum size, and abnormal asymmetry of the
      cerebellum and planum temporale structures). Functional MRI reports abnormal
      activation patterns in dyslexia during reading operations (e.g., aggregated
      studies observed under-activations in the left hemisphere fusiform and
      supramarginal. gyri and over-activation in the left cerebellum in dyslexic
      subjects compared with controls). Finally, diffusion tensor imaging reveals
      abnormal orientations in areas within the white matter micro-structures of
      dyslexic brains (e.g., aggregated studies reported a reduction of the fraction
      anisotropy values in bilateral areas within the white matter). Herein, we will
      discuss all of these MRI findings focusing on various aspects of implemented
      methodologies, testing databases, as well as the reported findings. Finally, the
      paper addresses the correlation between the MRI findings in the literature,
      various aspects of research challenges, and future trends in this active research
      field.

PMID- 25992419
TI  - Medical biofilms--nanotechnology approaches.
AB  - Biofilms are colonies of bacteria or fungi that adhere to a surface, protected by
      an extracellular polymer matrix composed of polysaccharides and extracellular
      DNA. They are highly complex and dynamic multicellular structures that resist
      traditional means of killing planktonic bacteria. Recent developments in
      nanotechnology provide novel approaches to preventing and dispersing biofilm
      infections, which are a leading cause of morbidity and mortality. Medical device
      infections are responsible for approximately 60% of hospital acquired infections.
      In the United States, the estimated cost of caring for healthcare-associated
      infections is approximately between $28 billion and $45 billion per year. In this
      review, we will discuss our current understanding of biofilm formation and
      degradation, its relevance to challenges in clinical practice, and new
      technological developments in nanotechnology that are designed to address these
      challenges.

PMID- 25992420
TI  - Molecular toxicity of nanomaterials.
AB  - With the rapid developments in the fields of nanoscience and nanotechnlogy, more
      and more nanomaterials and their based consumer products have been used into our
      daily life. The safety concerns of nanomaterials have been well recognized by the
      scientific community and the public. Molecular mechanism of interactions between
      nanomaterials and biosystems is the most essential topic and final core of the
      biosafety. In the last two decades, nanotoxicology developed very fast and
      toxicity phenomena of nanomaterials have been reported. To achieve better
      understanding and detoxication of nanomaterials, thorough studies of nanotoxicity
      at molecular level are important. The interactions between nanomaterials and
      biomolecules have been widely investigated as the first step toward the molecular
      nanotoxicology. The consequences of such interactions have been discussed in the
      literature. Besides this, the chemical mechanism of nanotoxicology is gaining
      more attention, which would lead to a better design of nontoxic nanomaterials. In
      this review, we focus on the molecular nanotoxicology and explore the toxicity of
      nanomaterials at molecular level. The molecular level studies of nanotoxicology
      are summarized and the published nanotoxicological data are revisited.

PMID- 25992421
TI  - Lung toxicity of biodegradable nanoparticles.
AB  - Biodegradable nanoparticles exhibit high potentialities for local or systemic
      drug delivery through lung administration making them attractive as nanomedicine
      carriers. However, since particulate matter or some inorganic manufactured
      nanoparticles exposed to lung cells have provoked cytotoxic effects, inflammatory
      and oxidative stress responses, it becomes important to investigate nanomedicine
      toxicity towards the lungs. This is the reason why, in the present review, the
      behavior of biodegradable nanoparticles towards the different parts of the
      respiratory tract as well as the toxicological consequences, measured on several
      models in vitro, ex vivo or in vivo, are described. Taken all together, the
      different studies carried out so far conclude on no or slight toxicity of
      biodegradable nanoparticles.

PMID- 25992422
TI  - Extracellular miRNAs: origin, function and biomarkers in hepatic diseases.
AB  - MicroRNAs (miRNAs), a class of 19-24 nucleotides non-coding RNAs, regulate gene
      expression by inhibiting both translation and stability of specific mRNAs at the
      post-transcriptional level. The existence of miRNAs in a series of mammalian body
      fluids as extracellular nuclease-resistant entities, together with the aberrant
      expression of miRNAs during the occurrence and development of a wide range of
      diseases, triggers the possibility that miRNAs as promising noninvasive
      diagnostic biomarkers are applied to predict the pathological status of the body.
      However, the origin and biological function of extracellular miRNAs have not been
      systematically elucidated. In this review, we summarize the current literature on
      the biogenesis and post-transcriptional regulation of miRNAs, discuss available
      evidence regarding the possible origin and release of extracellular miRNAs, and
      collect novel views on their potentials as key mediators in cell-cell
      communication processes. Finally, we shed light on the accumulating knowledge
      about their utilities as diagnostic biomarkers in hepatic diseases.

PMID- 25992424
TI  - Multifunctional magnetoplasmonic nanomaterials and their biomedical applications.
AB  - Multifunctional magnetoplasmonic (Au-Fe(x)O(y)) nanomaterials are characterized
      by some features of iron oxide and gold, such as surface chemistry, special
      optical properties, and superparamagnetic properties, which have helped to draw
      much attention to their biomedical applications. In this review, the state of the
      art of this rapidly developing field is described. We review the developments in
      different approaches to integrating the magnetic and plasmonic properties in a
      single nanoparticle with different morphological traits. Specific plasmonic and
      magneto-optical properties of magnetoplasmonic nanoparticles are explained; this
      information should shed light on the future development of multifunctional
      magnetoplasmonic nanomaterials. We also review cytotoxicity of magnetoplasmonic
      nanoparticles by in vitro and in vivo studies. With the multifunctional
      properties of magnetoplasmonic nanomaterials, a variety of applications such as
      biosensor, bioseparation, multimodal imaging, and therapeutics is possible and is
      highlighted here, in addition to outlining the future trends and perspectives of
      these sophisticated nanocomposites.

PMID- 25992423
TI  - Preparation and biomedical applications of chitin and chitosan nanofibers.
AB  - Chitin (beta-(1-4)-poly-N-acetyl-D-glucosamine) is widely distributed in nature
      and is the second most abundant polysaccharide after cellulose. Chitin occurs in
      nature as ordered macrofibrils. It is the major structural component in the
      exoskeleton of crab and shrimp shells and the cell wall of fungi and yeast. As
      chitin is not readily dissolved in common solvents, it is often converted to its
      more deacetylated derivative, chitosan. Chitin, chitosan, and its derivatives are
      widely used in tissue engineering, wound healing, and as functional foods.
      Recently, easy methods for the preparation of chitin and chitosan nanofibers have
      been developed, and studies on biomedical applications of chitin and chitosan
      nanofibers are ongoing. Chitin and chitosan nanofibers are considered to have
      great potential for various biomedical applications, because they have several
      useful properties such as high specific surface area and high porosity. This
      review summarizes methods for the preparation of chitin and chitosan nanofibers.
      Further, biomedical applications of chitin and chitosan nanofibers in (i) tissue
      engineering, (ii) wound dressing, (iii) cosmetic and skin health, (iv) stem cell
      technology, (v) anti-cancer treatments and drug delivery, (vi) anti-inflammatory
      treatments, and (vii) obesity treatment are summarized. Many studies indicate
      that chitin and chitosan nanofibers are suitable materials for various biomedical
      applications.

PMID- 25992425
TI  - Ferritin nanocages: a novel platform for biomedical applications.
AB  - Ferritin is a ubiquitous iron storage protein responsible for maintaining the
      iron homeostasis in living organism and thereby protects the cell from oxidative
      damage. The ferritin protein cages have been used as a reaction vessel for the
      synthesis of various non-native metallic nanoparticles inside its core and also
      used as a nanocarrier for various applications. Lack of suitable non-viral
      carrier for targeted delivery of anticancer drugs and imaging agents is the major
      problem in cancer therapy and diagnosis. The pH dependent reversible assembling
      and disassembling property of ferritin renders it as a suitable candidate for
      encapsulating a variety of anticancer drugs and imaging probes. Ferritins
      external surface is chemically and genetically modifiable which can serve as
      attachment site for tumor specific targeting peptides or moieties. Recent
      studies, further establishes ferritin as a multifunctional nanocarrier for
      targeted cancer diagnosis and therapy. Moreover, the biological origin of these
      protein cages makes it a biocompatible nanocarrier that stabilizes and protects
      the enclosed particles from the external environment without provoking any toxic
      or immunogenic responses. This review mainly focuses on the application of
      ferritin nanocages as a novel non-viral nanocarrier for cancer therapy and it
      also highlights various biomedical applications of ferritin nanocages.

PMID- 25992426
TI  - Anodic growth and biomedical applications of TiO2 nanotubes.
AB  - Over the past decades, self-assembled, vertically-aligned nanotubes have been
      generated on metallic substrates via anodization, which attracted significant
      scientific interest for a broad range of applications. These nano-tubular
      structures integrate highly controllable geometry at the nano-scale with
      fascinating chemical and biological properties. In this review, we first
      discussed mechanistic aspects of nanotube growth primarily on titanium (Ti)
      substrates by controlled anodization, a relatively inexpensive and scalable
      electrochemical process. We thoroughly reviewed electrochemical conditions that
      led to formation of self-assembled, vertically-aligned nano-tubular layers as
      they apply primarily to Ti substrates; we also reviewed anodization conditions
      that have led to formation of nanotubes on zirconium and various Ti alloys. We
      discussed how to adjust a set of anodization parameters to fine-tune the geometry
      of vertically oriented titania (TiO2) nanotubes, such as nanotube diameter, wall
      thickness, and length. We critically analyzed the key anodization parameters in
      the literature, including applied voltage, anodization duration, voltage ramp,
      electrolyte composition and concentration, electrolyte pH, electrolyte
      temperature, and electrolyte fluoride and water concentrations. Lastly, we
      discussed the promising properties of anodically grown TiO2 nano-tubular arrays
      for a wide range of biomedical applications, including directing cell
      bioactivity, anti-bacterial efficacy, modulating deposition of hydroxyapatite,
      drug delivery, biosensors, and orthopedic implants (in vivo). We highlighted
      ongoing in vitro and in vivo studies on the effects of nanotube geometry and
      aspect ratio on their hydrophilicity and interactions with biological entities at
      the protein, cellular and tissue level.

PMID- 25992427
TI  - Surface functionalized selenium nanoparticles for biomedical applications.
AB  - Selenium nanoparticles present an enhanced genetic actions and possess superior
      adsorptive capacity due to the interaction between the nanoparticles and NH, C=O,
      COO- and C-N groups of proteins. This review is focused on the biomedical
      applications of surafce funtionalized selenium nanoparticles. The engineering of
      exterior surface of the selenium nanoparticles has further emphasizing on the
      recent progresses in regulating monolayer structures for competent delivery of
      drugs and biomolecules. Crucial queries of transport, uptake, and clearance are
      discussed and illustrated through the prospects of selenium nanoparticles. The
      work presents an insight of how biomedical research can evolve with selenium
      nanoparticles and where we see the field is heading in the near future.

PMID- 25992428
TI  - Progress in selection and biomedical applications of aptamers.
AB  - Aptamers are short single-stranded DNA or RNA, which can be selected from random
      combinatorial library by SELEX in vitro. The SELEX technology has been modified
      over the years in different ways to become more efficient and less time
      consuming, to reach higher affinities of the aptamers and for automation of the
      process. The multitude of different targets used in SELEX implicates aptamers are
      possible to be selected using any target theoretically. This paper presents the
      SELEX technology screening aptamers and its latest progress including modified
      selection methods (negative SELEX, counter SELEX and substractive SELEX) and
      efficient selection methods (CE-SELEX, non-SELEX, automated-SELEX and
      microfluidic SELEX). Additionally, cell SELEX using whole cells as targets is
      introduced. Varieties of live pathogenic organisms and many cancer cells have
      been used as targets for cell SELEX. Finally, an overview of biomedical
      applications of aptamers is given. Aptamers as a class of biorecognition elements
      that possess many advantages such as high specificity and binding affinity, easy
      synthesis, easy modification, small size, non-toxicity and good stability, have
      been increasingly applied in biomedical field. Especially, the combination of
      aptamers with nanomaterials will continuously play more and more important roles
      in many applications such as detection of targets, diagnosis and treatment of
      diseases, bioimaging, and drugs delivery.

PMID- 25992429
TI  - Structure, properties and applications of mussel-inspired polydopamine.
AB  - Mussel-inspired polydopamine (PDA) has emerged as a promising molecule used for
      anchoring synthetic and biological substances or forming an adhesive layer onto
      various substrates for biomedical and nanotechnology applications because of its
      outstanding properties. This review article provides an overview of the recent
      progress in the PDA-based materials, including synthesis of nanoparticles,
      capsules, structure-mechanism, physicochemical and biological properties, and
      medical applications. Frist, to understand how PDA nanoparticles, capsules and
      films produce the unique properties is insight on the processing parameters.
      Next, we highlight what is known regarding the mechanism of self-polymerization
      and the structure features of dopamine (DA), which is based on the formation of
      covalent bond or through a combination mode between monomers. The inherent
      hydrophilicity and adhesive property of PDA with the coexistence of catechol and
      amine functionalities provide desirable surface characteristics without the need
      for further modification. Finally, successful applications, such as grafting
      substances, biomineralization, antifouling and antibacterial coatings, drug/gene
      delivery, and tissue engineering, reported to date involving PDA will be focused.
      The future study of PDA to develop novel materials with unique properties is
      emerging for specific nanomedicine applications.

PMID- 25992430
TI  - Recent developments in scaffold-guided cartilage tissue regeneration.
AB  - Articular cartilage repair is one of the most challenging problems in biomedical
      engineering because the regenerative capacity of cartilage is intrinsically poor.
      The lack of efficient treatment modalities motivates researches into cartilage
      tissue engineering such as combing cells, scaffolds and growth factors. In this
      review we summarize the current developments on scaffold systems available for
      cartilage tissue engineering. The factors that are critical to successfully
      design an ideal scaffold for cartilage regeneration were discussed. Then we
      present examples of selected material types (natural polymers and synthetic
      polymers) and fabricated forms of the scaffolds (three-dimensional scaffolds,
      micro- or nanoparticles, and their composites). In the end of review, we conclude
      with an overview of the ways in which biomedical nanotechnology is widely applied
      in cartilage tissue engineering, especially in the design of composite scaffolds.
      This review attempts to provide recommendations on the combination of qualities
      that would produce the ideal scaffold system for cartilage tissue engineering.

PMID- 25992431
TI  - Applications of carbon nanomaterials in bone tissue engineering.
AB  - In the biomedical field, remarkable advancements have been made in artificial
      biomaterials for treating bone loss or defects. A variety of synthetic polymers,
      natural polymers and bioceramics are being used to develop artificial bones. Many
      natural and synthetic biomaterials, which are being investigated for their
      physiochemical role in vivo, are currently in the clinical trial stage. Carbon
      based prostheses are promising materials that mimic the natural function of bone,
      e.g., mechanical strength. Recently, carbon-based bone materials, such as carbon
      nanotubes and graphene, have been widely investigated as potential solutions to
      several biomedical problems. This review summarizes the biophysicochemical and
      biomedical properties of carbon nanomaterials composed of polymer and ceramic
      structures and discusses their functionality in bone tissue engineering.

PMID- 25992432
TI  - Nano-hydroxyapatite composite biomaterials for bone tissue engineering--a review.
AB  - In recent years, significant development has been achieved in the construction of
      artificial bone with ceramics, polymers and metals. Nano-hydroxyapatite (nHA) is
      widely used bioceramic material for bone graft substitute owing to its
      biocompatibility and osteoconductive properties. nHA with chitin, chitosan,
      collagen, gelatin, fibrin, polylactic acid, polycaprolactone, poly(lactic-co
      glycolic) acid, polyamide, polyvinyl alcohol, polyurethane and
      polyhydroxybutyrate based composite scaffolds have been explored in the present
      review for bone graft substitute. This article further reviews the preparative
      methods, chemical interaction, biocompatibiity, biodegradation, alkaline
      phosphatase activity, mineralization effect, mechanical properties and delivery
      of nHA-based nanocomposites for bone tissue regeneration. The nHA based composite
      biomaterials proved to be promising biomaterials for bone tissue engineering.

PMID- 25992433
TI  - Nano-biomimetics for nano/micro tissue regeneration.
AB  - Nanostructured biomimetics have recently shown great promise in the field of
      tissue engineering. They can be used as nanoscaffolds and tailored at the
      molecular level. The scaffold topography closely resembles the native
      extracellular matrix in terms of framing, porosity and bio-functionality. This
      review covers the approaches used for biomimetic fabrication, including soft
      lithography, the plasmonic nanohybrid matrix method and multilayer self-assembly
      scaffolds for tissue regeneration. It brings together knowledge from different
      arenas about the synthesis, characterization and functionalization of matrices to
      accelerate the tissue regeneration process. Every tissue in the body presents
      different challenges and requires a specific fabrication process designed to
      identify and mirror the particular organ. For example, microfluidics systems aim
      to mimic the extracellular matrix of vascular and cartilage tissue, and these
      systems have different parts with completely different mechanical strength,
      cellular adhesion and interplay between matrix and cells. A fully functional
      nanomatrix designed by a self-assembling methodology for use as a vascular tissue
      engineering scaffold needs to have intrinsic microvessels that facilitate the
      transportation of metabolites and nutrients. Similarly, in the case of peripheral
      nerve regeneration, a scaffold needs to have sufficient mechanical strength to
      protect the regenerating tissue, yet be biodegradable enough to avoid a possible
      second surgery. To enhance the functionality of scaffolds, increasing focus has
      been placed on in vitro and in vivo research to achieve optimal scaffold design.
      Nanobiomimetics unarguably offer the most suitable physicochemical scaffold
      properties for tissue regeneration.

PMID- 25992434
TI  - Smart nanomaterials for biomedics.
AB  - Nanotechnology has become important in various disciplines of technology and
      science. It has proven to be a potential candidate for various applications
      ranging from biosensors to the delivery of genes and therapeutic agents to tissue
      engineering. Scaffolds for every application can be tailor made to have the
      appropriate physicochemical properties that will influence the in vivo system in
      the desired way. For highly sensitive and precise detection of specific signals
      or pathogenic markers, or for sensing the levels of particular analytes,
      fabricating target-specific nanomaterials can be very useful. Multi-functional
      nano-devices can be fabricated using different approaches to achieve multi
      directional patterning in a scaffold with the ability to alter topographical cues
      at scale of less than or equal to 100 nm. Smart nanomaterials are made to
      understand the surrounding environment and act accordingly by either protecting
      the drug in hostile conditions or releasing the "payload" at the intended
      intracellular target site. All of this is achieved by exploiting polymers for
      their functional groups or incorporating conducting materials into a natural
      biopolymer to obtain a "smart material" that can be used for detection of
      circulating tumor cells, detection of differences in the body analytes, or repair
      of damaged tissue by acting as a cell culture scaffold. Nanotechnology has
      changed the nature of diagnosis and treatment in the biomedical field, and this
      review aims to bring together the most recent advances in smart nanomaterials.

PMID- 25992435
TI  - A special issue on reviews in nanomedicine, drug delivery and vaccine
      development.
AB  - This thematic special issue of the Journal of Biomedical Nanotechnology focused
      on the "Reviews in Nanomedicine, Drug Delivery and Vaccine Development" contains
      30 state-of-the-art review articles covering recent advances, trends and future
      directions emphasized on nanoparticle-based new strategies for diagnosis and
      cancer phototherapies, nanomedicine, nucleic acid-based nanocarriers, gene and
      drug delivery systems, tuberculosis mucosal and H5N1 influenza vaccines, drug
      loaded electrospun polymer nanofibers, microneedle technology for insulin
      delivery for the treatment of insulin-dependent diabetes mellitus, RNA-based
      therapies, nanotoxicity and biosafety of nanomaterials to environment and human
      health.

PMID- 25992436
TI  - Testing nanoparticles for angiogenesis-related disease: charting the fastest
      route to the clinic.
AB  - Recently, nanoparticles (NPs) have been established as ideal drug delivery
      vehicles for treating cancer. This is due to the enhanced permeability and
      retention (EPR) effect that is a direct result of the angiogenic nature of the
      tumor tissue and its ability to sequester chemotherapeutics from healthy tissues.
      Ideal drug delivery nanocarriers will exploit the EPR effect, accumulate in the
      tumorous tissue, and be able to release the drugs at a high concentration where
      needed, thereby reducing undesirable side effects. In order to determine ideal NP
      qualities that enable drugs to be delivered in such a manner, extensive testing
      in biological systems is required. However, it is impractical to study new
      potential nanocarriers in humans or in mammalian models due to the potential
      adverse consequences, low throughput, and high cost. Simpler models would allow
      for higher throughput screening of nanocarrier vehicles. This review outlines the
      most recent advances in alternative model assays and their significance in
      testing NPs en route to the clinic. In decreasing complexity, we examine
      zebrafish embryos, the chorioallantoic membrane of the chicken embryo, multicell
      static and flow-based assays, and single cell assays for efficacy, accuracy and
      utility as predictors for human therapeutic outcomes.

PMID- 25992437
TI  - Nanoparticle enhanced optical imaging and phototherapy of cancer.
AB  - Nanoparticle research has seen advances in many fields, including the imaging and
      treatment of cancer. Specifically, nanotechnology has been investigated for its
      potential to be used as a tool to deliver well-tested drugs in potentially safer
      concentrations through both passive and active tumor targeting, while
      additionally providing means for a secondary therapy or imaging contrast. In
      particular, the use of light in conjunction with nanoparticle-based imaging and
      therapies has grown in popularity in recent years due to advances in utilizing
      light energy. In this review, we will first discuss nanoparticle platforms that
      can be used for optical imaging of cancer, such as fluorescence generation with
      quantum dots and surface-enhanced Raman scattering with plasmonic nanoparticles.
      We then analyze nanoparticle therapies, including photothermal therapy,
      photodynamic therapies, and photoacoustic therapy and their differences in
      exploiting light for cancer treatment. For photothermal therapies in particular,
      we have aggregated data on key variables in gold nanoparticle treatment
      protocols, such as exposure energy and nanoparticle concentration, and hope to
      highlight the need for normalization of variable reporting across varying
      experimental conditions and energy sources. We additionally discuss the potential
      to co-deliver chemotherapeutic drugs to the tumor using nanoparticles and how
      light can be harnessed for multifunctional approaches to cancer therapy. Finally,
      current in vitro methods of testing these therapies is discussed as well as the
      potential to improve on clinical translatability through 3D tissue phantoms. This
      review is focused on presenting, for the first time, a comprehensive comparison
      on a wide variety of photo based nanoparticle interactions leading to novel
      treatments and imaging tools from a basic science to clinical aspects and future
      directions.

PMID- 25992438
TI  - Applications of nanoparticles for brain cancer imaging and therapy.
AB  - The most common types of malignant brain tumors in adults are brain metastasis
      and primary glioblastoma multiforme (GBM), both of which are highly lethal, with
      a median survival of less than a year. A critical challenge in treating brain
      tumors is the delivery of drugs to the central nervous system (CNS). The blood
      brain barrier (BBB), which has been shown to be partially disruptive even in the
      late stage of these brain tumors, prevents the access of therapeutic
      concentrations of systemic drugs to the tumor in brain parenchyma. Nanoparticle
      systems can represent optimal carriers for delivery of therapeutic agents. We
      will summarize various strategies used to improve nano-delivery of imaging
      contrast or therapeutic agents across BBB to brain tumors. Recent advances in
      molecular and cellular identifications of neurooncological biomarkers promise the
      advent of nanotechnology-based brain tumor-targeted detection and therapy. In
      this review, we will further discuss the current understanding of brain tumor
      biology and tumor type-specific genetic and epigenetic alterations, and advances
      in development of the novel nanoparticles for brain tumor imaging and therapy.

PMID- 25992439
TI  - Red blood cells as carriers of iron oxide-based contrast agents for diagnostic
      applications.
AB  - New biomedical strategies are being developed to improve disease detection,
      therapeutic monitoring, and treatment efficacy in several contexts for example in
      anti-angiogenic chemotherapy, and prevention of cardiovascular disorders. The use
      of contrast agents to improve the sensitivity and resolution of diagnostic
      imaging modalities, detect lesions or organs, and evaluate organ function was
      immediately recognized. In the last years, superparamagnetic iron oxide (SPIO)
      nanoparticles have been clinically used as MRI contrast agents for the diagnosis
      of liver diseases, due to their ability to shorten T2* relaxation times. After
      the intravenous administration, SPIO nanoparticles are rapidly eliminated from
      the bloodstream since they are selectively taken up by the Kupffer cells in the
      liver, spleen, and bone marrow thus improving the clinical tumor detection in
      these tissues. However, for the investigation of vascular system including
      functional cardiac diagnosis, angiography and cardiac wall motion assessment,
      contrast agents with long blood circulation time would be necessary. In fact,
      imaging applications for long-term monitoring require the repeated administration
      of SPIO bolus injections, which complicates quantitative comparisons due to the
      temporal variations in concentration. In this context, researchers have developed
      several SPIO delivery systems based on red blood cells (RBCs) used as carriers to
      increase the blood circulation time of contrast agents. Encapsulation of SPIOs
      into RBCs appears the most attractive strategy to obtain magnetic RBC-constructs
      suitable for MRI and MPI analyses of blood vascular system.

PMID- 25992440
TI  - Anticancer use of nanoparticles as nucleic acid carriers.
AB  - Advances in nanotechnology opened up new horizons in the field of cancer
      research. Nanoparticles made of various organic and inorganic materials and with
      different optical, magnetic and physical characteristics have the potential to
      revolutionize the way we diagnose, treat and follow-up cancers. Importantly,
      designs that might allow tumor-specific targeting and lesser side effects may be
      produced. Nanoparticles may be tailored to carry conventional chemotherapeutics
      or new generation organic drugs. Currently, most of the drugs that are commonly
      used, are small chemical molecules targeting disease-related enzymes. Recent
      progress in RNA interference technologies showed that, even proteins that are
      considered to be "undruggable" by small chemical molecules, might be targeted by
      small RNAs for the purpose of curing diseases, including cancer. In fact, small
      RNAs such as siRNAs, shRNAs and miRNAs can drastically change cellular levels of
      almost any given disease-associated protein or protein group, resulting in a
      therapeutic effect. Gene therapy attempts were failing mainly due to delivery
      viral vector-related side effects. Biocompatible, non-toxic and efficient
      nanoparticle carriers raise new hopes for the gene therapy of cancer. In this
      review article, we discuss new advances in nucleic acid and especially RNA
      carrier nanoparticles, and summarize recent progress about their use in cancer
      therapy.

PMID- 25992441
TI  - Multifunctional silica-based nanocomposites for cancer nanotheranostics.
AB  - Nanotheranostics have recently attracted increasing attention for their
      simultaneous drug delivery and diagnostic imaging of diseases, particularly in
      cancer treatment. Among various nanomaterials, silica nanoparticles are one the
      most popular models for nanotheranostics. With a tailored mesoporous structure
      and high surface area, silica nanoparticles show significant advantages over
      traditional drug nanocarriers as drug delivery systems. With versatile silicone
      chemistry, silica nanoparticles can incorporate multiple components with optical,
      magnetic, and electrical properties for imaging and therapy. In this review, we
      give an overview of the recent progress in the synthesis and biomedical
      application of multifunctional silica nanoparticles for multimodal imaging,
      combination therapy, and the nanotheranostics of cancer. We also include our
      personal perspectives on the direction in which future work in this field might
      be focused.

PMID- 25992442
TI  - Nanopharmaceutics: phytochemical-based controlled or sustained drug-delivery
      systems for cancer treatment.
AB  - This review is an attempt to assess the different classes of phytochemicals and
      some of their members which have been encapsulated into nanocarrier systems for
      their chemotherapeutic or chemopreventive properties. Given the broad spectrum of
      nanomedicines currently in clinical trial and clinical use from polymer-protein
      conjugates, through nanocrystals, nanogels, dendrimers to ethosomes, the focus of
      this review will be on block copolymer nanomicelles, nanoparticles, polymer-drug
      conjugates, liposomes and solid lipid nanocarriers (SLNs). The twenty
      phytochemicals investigated for encapsulation and targeted delivery were selected
      from a variety of classes intended to encompass the largest possible chemical
      compositions, namely flavonoids, aromatic acids, xanthones, terpenes, quinones,
      lignans and alkaloids. To the best of our knowledge, reviews on the
      nanoencapsulation of these phytochemicals and their delivery are not available.
      In this review, the issues associated with the limited use of each phytochemical
      in cancer therapy in humans are reviewed and the advantages of entrapment into
      nanocarriers are assessed in terms of drug loading efficiency, size of
      nanocarriers, drug release profiles and in vitro and/or in vivo testing specific
      to cancer research, e.g., cytotoxicity assay, cell inhibition/viability,
      scavenging of reactive oxygen species and biodistribution studies (elimination
      half-life and mean residence time).

PMID- 25992443
TI  - Recent advances in shell-sheddable nanoparticles for cancer therapy.
AB  - Cancer remains one of the most incurable diseases associated with high mortality
      and morbidity. Although extensive studies have been carried out for cancer
      therapy, there are still no gold standards available for treatment. Spurred by
      advances in biomaterial sciences, recent efforts have focused on the development
      of polymeric nanoparticles for site-specific delivery of anticancer drugs. Such
      nanoparticles have distinct characteristics, including high thermodynamic
      stability, good biocompatibility, and prolonged circulation in the bloodstream.
      Owing to these unique features, systemically administered nanoparticles can
      passively accumulate at tumor tissue with leaky vasculature and poor lymphatic
      drainage system, which is called the enhanced permeation and retention (EPR)
      effect. However, the site-specific accumulation of nanoparticles does not
      guarantee high antitumor efficacy because the conventional nanoparticles release
      the drugs in a sustained manner via the passive diffusion mechanism, which may
      not endow tumor tissue with cytotoxic local concentrations of the drugs. To
      surmount this limitation, nanoparticles that can rapidly release the drug at the
      tumor site need to be developed. In recent years, it has been demonstrated that
      shell-sheddable nanoparticles have an ability to rapidly release the drug by
      recognizing the specific environments of the tumor tissue. After systemic
      administration, shell-sheddable nanoparticles reach tumor sites via the EPR
      effect, followed by exposure to tumor microenvironment-specific stimuli which
      cause a burst release of the drug. Representative stimuli, used to design shell
      sheddable nanparticles, include pH, redox, enzymes, temperature, ultraviolet, and
      ultrasound. In this review, we discuss the recent advances in tumor-specific,
      shell-sheddable nanoparticles for drug delivery.

PMID- 25992444
TI  - Pulmonary multifunctional nano-oncological modules for lung cancer treatment and
      prevention.
AB  - Mortality associated with lung cancer and its metastasis has outnumbered those
      related to other forms of cancer. Despite being a directly accessible organ,
      conventional oncological strategies exhibiting prolific outcome in treatment and
      prevention of lung cancer is far from reality. This is attributed to numerous
      challenges posed by lung environment. The extracellular aura of lung comprises
      immensely complicated structures, ciliary escalators, omnipresence of mucus and
      alveolar fluid, and macrophagial uptake which presents an array of impediments to
      the arrival of therapeutic moiety at the tumor site. Besides these, intracellular
      obstacles viz enzymatic degradation, cell membrane translocation, endosomal
      escape and/or nuclear entry also limit superior therapeutic efficacy. The current
      review elaborates wide-ranging challenges to lung cancer treatment and its
      circumvention by latest developments in multifunctional nano-oncological modules
      delivered via the pulmonary route-which smartly deal with the abovementioned
      issues and bestow positivity to this complication.

PMID- 25992445
TI  - Antitumor therapy using nanomaterial-mediated thermolysis.
AB  - Nanomaterial-based systems present several novel therapeutic opportunities for
      cancer therapy based solely upon their unique physical and chemical properties.
      Despite advances in current cancer treatment, collateral damage to neighboring
      healthy tissues still cannot be avoided. By exploiting the strong optical and/or
      electromagnetic properties offered by nanomaterials, they are being employed as
      thermal nanoscalpels for the ablation of cancer cells. Through surface
      functionalization, these nanomaterials can be specifically targeted to tumorous
      tissue allowing for an increase in therapeutic potential and reduction in side
      effects. Moreover, these features provide nanomaterials with a tunable surface
      which can be used to modify optical, magnetic, thermal and mechanical properties.
      This review highlights carbon nanomaterials, nanogolds, magnetic nanoparticles
      and emerging hybrids applied for the thermolysis of cancer cells.

PMID- 25992446
TI  - SiRNA-based therapies for pulmonary diseases.
AB  - Various delivery strategies, involving siRNA as a therapeutic tool for gene
      silencing, have been highlighted through several investigations all over the
      world. One such medical target, where the siRNA-based therapies have been
      immensely explored and have met with considerable success, is the area of
      pulmonary disorders. Lung diseases have presented themselves as attractive
      targets for studying siRNA-mediated cures due to their widespread persistence and
      lethality. Another interesting feature in this case is that the lung is
      accessible to therapeutic agents via multiple administration routes including the
      nasal, oral and intravenous routes. Recent advances in pulmonary delivery
      highlight the exploitation of all these routes for administration of siRNA-based
      therapies, particularly by employing non-viral carriers like nanoparticles.
      Through this manuscript we aim to provide a comprehensive overview of the most
      important and the latest developments in non-viral siRNA delivery for lung
      diseases. We have focused our discussion on the diverse systems, which have been
      investigated for a plethora of pulmonary disorders, ranging from inflammatory
      conditions like asthma and COPD, to infectious diseases like tuberculosis, and to
      lung cancer. An overview of the preclinical and clinical investigations conducted
      in this area has also been presented to the readers. While a variety of these
      systems have been found to be promising in pre-clinical studies, their successful
      transition as therapeutics will ultimately depend upon their clinical safety and
      efficacy, as well as the specificity of the carriers and methods employed for
      their administration.

PMID- 25992447
TI  - RNA interference-based therapeutics: molecular platforms for infectious diseases.
AB  - The potential uses and therapeutic benefits of RNA interference (RNAi) are
      enormous. Recent insights into RNAi technologies have highlighted their role in
      analyzing the functions and regulation of gene expression in eukaryotes and
      further utilizing this information for identification and amelioration of many
      diseases. These studies have also established the role of RNAi mediated post
      transcriptional gene silencing (PTGS) mechanism in mammals by several endogenous,
      gene regulation systems including small interfering RNAs (siRNA), micro RNA
      (miRNA) and small hairpin RNAs (shRNA). Moreover, these RNAi-based therapeutics
      have demonstrated the capability to silence therapeutically relevant genes in
      various in vivo models of cancer, infections autoimmune diseases and other
      genetic disorders. Over the past few decades, infectious diseases have been one
      of the leading causes of death around the world. Ubiquitously, intracellular
      obligate or facultative microorganisms cause serious or fatal infections and
      associated diseases in humans. Currently available literature suggests that
      infections caused by intracellular pathogens present an intriguing area, wherein
      RNAi technology may be effectively employed to neutralize the harmful effects of
      various intracellular pathogens. In this manuscript, we have emphasized on the
      challenges and opportunities involved in the therapy of such intracellular
      infections, especially employing RNAi-based interventions. We have focused our
      discussion on the current state-of-the-art RNAi-based therapies, which have been
      explored for various intracellular infections mediated by bacteria, fungi,
      viruses and protozoa. Nanocarrier mediated delivery of siRNA and shRNA molecules
      have also been found to overcome the various delivery challenges of these
      biotherapeutics; these have also been briefly summarized here. Furthermore, the
      outcomes and progresses that have been made in pre-clinical models and clinical
      trials have also been presented to review the numerous challenges encountered so
      far. Finally, we have also addressed the various future perspectives that could
      overcome these challenges and accelerate the progress and commercial success of
      these systems.

PMID- 25992448
TI  - Heart-targeted nanoscale drug delivery systems.
AB  - The efficacious delivery of drugs to the heart is an important treatment strategy
      for various heart diseases. Nanocarriers have shown increasing promise in
      targeted drug delivery systems. The success of nanocarriers for delivering drugs
      to therapeutic sites in the heart mainly depends on specific target sites,
      appropriate drug delivery carriers and effective targeting ligands. Successful
      targeted drug delivery suggests the specific deposition of a drug in the heart
      with minimal effects on other organs after administration. This review discusses
      the pathological manifestations, pathogenesis, therapeutic limitations and new
      therapeutic advances in various heart diseases. In particular, we summarize the
      recent advances in heart-targeted nanoscale drug delivery systems, including
      dendrimers, liposomes, polymer-drug conjugates, microparticles, nanostents,
      nanoparticles, micelles and microbubbles. Current clinical trials, the commercial
      market and future perspective are further discussed in the conclusions.

PMID- 25992449
TI  - Genetic engineering of bio-nanoparticles for drug delivery: a review.
AB  - Techniques using nanotechnology in the detection and treatment of cancers have
      made great progress in multidisciplinary fields. The advances in drug delivery
      systems (DDSs) have been supported mainly by the development of varied
      nanoparticles (NPs). Although the NPs based on organic and inorganic materials
      are integral parts in DDSs, bio-nanoparticles containing biopolymer and virus
      like particles (VLPs) are attractive biomaterials for DDSs because of their
      unique features originating in bio-based materials, such as biocompatibility,
      biodegradability and low immunogenicity. It is notable that these NPs
      additionally have a great advantage to enable the easy and flexible alteration of
      their features by genetic engineering approaches. Controlling the sequence and
      oligomeric process of polypeptide genes permits a variety of choices in type or
      size of biopolymeric NPs (e.g., elastin-like polypeptide NPs). In contrast, the
      functional genes are often inserted into the coding sequences for self-assembled
      proteins to give the VLPs (e.g., hemagglutinating virus of Japan, adeno
      associated virus, human immunodeficiency virus-1, simian virus 40 and hepatitis B
      virus) additional functions. Thus, genetic engineering readily allow alterations
      of the properties of NPs (e.g., particle shape, size and stability) and grant of
      new abilities (e.g., cell-specificity and drug loading and release). In this
      review, we introduce recent advances in bio-nanoparticles from the standpoint of
      engineering.

PMID- 25992450
TI  - Surface-engineered graphene-based nanomaterials for drug delivery.
AB  - Graphene, as a newly discovered carbon allotrope, has attracted broad interest
      and intense attention since its discovery for both fundamental research and a
      vast array of industrial and biomedical applications. Considerable efforts have
      been devoted to understanding the nano-bio-interfaces of graphene-based materials
      for exploring their potential biomedical applications, including drug delivery,
      biosensing, biomedical imaging, stem cell technology, and photothermal therapy.
      This review summarizes the current studies on the physiological stability,
      enhanced permeability and retention (EPR) effect, active targeting and drug
      carrying capability of graphene-based nanomaterials, and it provides a basic
      understanding about the mechanisms of drug and gene delivery by these
      nanomaterials. Also reviewed is the recent progress on photosensitizers and
      theranostics using graphene-based nanomaterials. The biosafety of graphene at the
      cellular and animal levels is discussed. The challenges and perspectives of the
      field are addressed.

PMID- 25992451
TI  - Carbohydrate based nanoparticles for drug delivery across biological barriers.
AB  - In this review, we will summarize the particularities of each of the following
      barriers from the point of view of drugs passing across them; blood brain
      barrier, ocular barriers, skin and mucosal barriers. Also, for each biological
      barrier the most representative examples of polysaccharides and cyclodextrins
      nanoformulations are presented.

PMID- 25992452
TI  - Polysaccharides as nanocarriers for therapeutic applications.
AB  - Nanocarriers have shown tremendous potential for the target-specific delivery of
      proteins, genes and drugs. Nanoparticles are fabricated using different natural
      and synthetic polymers. Natural polysaccharides are often used as building block
      for developing nano-sized drug delivery vehicles. The physicochemical properties
      of these materials, such as excellent biocompatibility, low cytotoxicity, surface
      charges that interact with DNA, protein and RNA, and cost effectiveness, make
      them exceptional base materials for nanocarrier fabrication. The mechanism for
      the complex formation of polysaccharides-DNA includes the electrostatic
      interactions between cationic polymers and anionic DNA to form polyplexes that
      offer unique possibilities for overcoming cellular barriers by escaping endosomal
      trafficking followed by cellular internalization and, consequently, enhancing the
      efficacy of drug and macromolecule delivery to targeted cells and tissue.
      Depending upon the cellular uptake and trafficking, nanocarriers are designed for
      different pharmacological and therapeutic applications. However, specific
      targeting that improves delivery remains an unsolved challenged. The process by
      which nanocarriers enter cells has important consequences not only for fate of
      these particles but also for biological systems and therapeutic applications.

PMID- 25992453
TI  - Drug loading and release from electrospun biodegradable nanofibers.
AB  - This review explores the potential of electrospun nanofibers for drug delivery
      applications. In the first section, some of the key challenges in drug delivery
      as well as the promise of electrospun drug loaded nanofibers are highlighted.
      Techniques of drug incorporation into nanofibers such as blending, surface
      modification and co-axial electrospinning are detailed. The major requirements of
      drug eluting scaffolds such as biocompatibility and biodegradability, efficient
      drug control and release, and adequate mechanical performance are addressed. Drug
      release kinetics, biodegradability and mechanical properties can be controlled by
      careful selection of polymers and electrospinning processing parameters while
      biocompatibility of electrospun mats may be enhanced through surface modification
      of the nanofibers. The major applications as well as the routes of administration
      of the drug-loaded electrospun nanostructures are discussed. Currently available
      drug eluting nanofibrous mats for applications ranging from cancer therapy to
      wound dressings as well as their preclinical trials are also reviewed.

PMID- 25992454
TI  - Production of drug-loaded polymeric nanoparticles by electrospraying technology.
AB  - The pharmaceutical industry struggles with high attrition. The outbreak of
      pharmaceutical micro/nanotechnology has been fundamental to overcome several
      (bio)pharmaceutic drawbacks of drugs such as poor aqueous solubility,
      physicochemical instability, short half life, inappropriate biodistribution and
      toxicity. The spatiotemporal release of drugs directly in the site of action and
      the restriction of the systemic exposure by means of nanotechnology has
      notoriously improved drug safety ratios. At the same time, the development of
      production methods that are cost-effective, scalable and reproducible under
      industrial settings becomes crucial to ensure the clinical translation of any
      development. The electrospraying process, also known as electrohydrodynamic
      atomization (EHDA), is a single-stage technique of liquid atomization by means of
      electrical forces that enables the generation of micro/nanoparticles with
      especially narrow size distribution. EHDA is based on the ability of an electric
      field to deform the interface of a liquid drop and break it into smaller mono
      disperse droplets. The main advantageous features over conventional methods are
      the possibility to produce particles without the use of surfactants, at ambient
      temperature and pressure and with maximum encapsulation efficiency due to the
      absence of an external medium that allows the migration and/or dissolution of
      water-soluble cargos. In addition, the mild conditions are optimal for the
      encapsulation of thermo-sensitive cargos. The present article overviews the
      applications of this technology for the production of nano-drug delivery systems
      and discusses its key role to support the transfer of a broad spectrum of
      nanomedicines to the market.

PMID- 25992455
TI  - Nanotechnological strategies for vaginal administration of drugs--a review.
AB  - Women frequently develop disorders related to the vaginal area, including
      problems with the immune system, hygiene, genetic aspects and sexually
      transmitted diseases. Compared with other mucosal application sites, the vagina
      represents local effect as well as systemic drug delivery and is able to avoid
      the first-pass effect due to its large surface area, high blood supply and
      permeability to many active ingredients. It has been widely proposed that the use
      of drugs to treat vaginal disorders be combined with nanotechnology because
      nanosystems often potentiate the action of most active constituents, reducing the
      required dosage and side effects and improving the resulting activity in
      comparison with conventional treatments. Following the trend of using drug
      delivery systems based on nanotechology, many studies have encouraged the
      scientific community to turn to the development of new strategies for the vaginal
      administration of drugs. This study proposes to review the most common
      nanotechnology-based drug delivery systems that have been used to improve the
      effectiveness of active compounds administrated to treat vaginal disorders.

PMID- 25992456
TI  - Transdermal delivery of insulin via microneedles.
AB  - Treatment of insulin-dependent diabetes mellitus, also known as Type 1 diabetes
      mellitus, requires delivery of exogenous insulin via injection or pump. An
      alternative to syringe-based subcutaneous delivery of insulin involves use of
      microneedles. These < 300 MUm diameter, 50-900 MUm long needle shaped devices may
      be used for intradermal delivery of insulin. Benefits associated with microneedle
      based delivery of insulin include minimal training for use, painless insertion,
      as well as the potential to combine microneedles with sensors and drug delivery
      devices to create an autonomous artificial pancreas. In this review, the efforts
      of academic and industrial researchers over the past decade to examine the
      functionality of microneedles for delivery of insulin, including insulin
      containing nanomaterials, via in vitro, ex vivo, and in vivo studies are
      considered.

PMID- 25992457
TI  - Vaccine technologies against avian influenza: current approaches and new
      directions.
AB  - The potential epidemiological human pandemic resulting from highly pathogenic
      avian influenza (HPAI) H5N1 has been studied extensively since the identification
      of the virus in the Guangdong province of China. The majority of research has
      focused on the unique and severe histopathological lesions induced by the virus.
      The severe pathological presentation of these infections has also prompted
      interest in identifying preventive and therapeutic approaches against HPAI. The
      potential severity of a HPAI pandemic and the efforts to identify effective
      intervention strategies have led to many novel discoveries in vaccine and
      antiviral development that are critically examined in this review.

PMID- 25992458
TI  - Approaches to tuberculosis mucosal vaccine development using nanoparticles and
      microparticles: a review.
AB  - Next-generation vaccines for tuberculosis should be designed to prevent the
      infection and to achieve sterile eradication of Mycobacterium tuberculosis.
      Mucosal vaccination is a needle-free vaccine strategy that provides protective
      immunity against pathogenic bacteria and viruses in both mucosal and systemic
      compartments, being a promising alternative to current tuberculosis vaccines.
      Micro and nanoparticles have shown great potential as delivery systems for
      mucosal vaccines. In this review, the immunological principles underlying mucosal
      vaccine development will be discussed, and the application of mucosal adjuvants
      and delivery systems to the enhancement of protective immune responses at mucosal
      surfaces will be reviewed, in particular those envisioned for oral and nasal
      routes of administration. An overview of the essential vaccine candidates for
      tuberculosis in clinical trials will be provided, with special emphasis on the
      potential different antigens and immunization regimens.

PMID- 25992459
TI  - Nanoparticle based tailoring of adjuvant function: the role in vaccine
      development.
AB  - Vaccination is one of the most powerful therapeutic tools for prevention and
      management of various infective and non-infective diseases including malignancy.
      Mass vaccination is a great strategy for eradicating major infectious diseases
      throughout the world like small pox. Application of nanotechnology for antigen
      delivery is a unique area of research and development which can change the
      vaccination strategy and policy in future. Nanocarriers can enhance antigen
      presentation including modulation of antigen processing pathways according to the
      specific need. The current review explores the pros and cons of application of
      different nanomaterials for antigen presentation and vaccine development.

PMID- 25992460
TI  - Nanoparticles for DNA vaccine delivery.
AB  - Nanotechnology is the development of engineered devices or materials at the micro
      molecular level in the nanometer range. The properties of nanoparticles that
      these could be designed, manufactured and introduced into the human body, have
      led to its application in various fields of medicine. They are being used for
      construction of diagnostic devices, contrast agents, analytical tools, physical
      therapy, drug discovery and drug delivery vehicles. The DNA vaccines have been
      emerged as best remedy for problematic diseases being capable of producing
      humoral and cellular immune responses as well as the safest vaccines so far.
      There are a large number of infectious diseases against which traditional
      vaccines failed to respond effectively. Especially, viral diseases and cancer
      where DNA vaccines seem to be the better option. However, the magnitude of immune
      responses produced by them in primates is not sufficient to be used in human
      beings. There is an evidence that these immune responses can be augmented by
      using properly structured nano-sized particles that may avoid DNA degradation and
      facilitate targeted and controlled delivery to antigen presenting cells.
      Adsorption, formulation or encapsulation with particles has been found to
      stabilize DNA formulations. The use of nanoparticles for vaccine delivery is a
      platform technology and has been applied for delivery of a variety of existing
      and potential vaccines successfully.

PMID- 25992461
TI  - DNA nanotechnology and its applications in biomedical research.
AB  - DNA nanotechnology, which uses DNA as a material to self-assemble designed
      nanostructures, including DNA 2D arrays, 3D nanostructures, DNA nanotubes and DNA
      nanomechanical devices, has showed great promise in biomedical applications.
      Various DNA nanostructures have been used for protein characterization, enzyme
      assembly, biosensing, drug delivery and biomimetic assemblies. In this review, we
      will present recent advances of DNA nanotechnology and its applications in
      biomedical research field.

PMID- 25992462
TI  - Applications of nanoparticles in nanomedicine.
AB  - The highly tunable physical and optical properties and the ability to bind an
      ever expanding library of ligands have catapulted nanoparticles into nearly every
      discipline of scientific research. As nanoparticles inch closer to being fully
      deployed at the clinical level, some of the recent advances in the applications
      of nanoparticles in medicine are reviewed. From imaging and diagnostics to
      therapy and treatment, a variety of nanoparticles are presented along with their
      physical and optical properties to be used in a diverse array of medical
      applications. While other reviews are tailored to specific applications or to
      single nanoparticle types, this review aims to offer a more widespread view on
      visualization, diagnosis and treatment of disease with various types of
      nanoparticles.

PMID- 25992463
TI  - Lipid hydrolysis products affect the composition of infant gut microbial
      communities in vitro.
AB  - Some lipid hydrolysis products such as medium-chained NEFA (MC-NEFA), sphingosine
      and monoacylglycerols (MAG) possess antibacterial activity, while others,
      including oleic acid, are essential for the optimal growth of Lactobacillus
      species. Thus, changes in the concentrations of NEFA and MAG in the distal ileum
      and colon can potentially selectively modulate the composition of the gut
      microbiota, especially in early life when lipid absorption efficacy is reduced.
      As medium-chained fatty acids are enriched in mothers' milk, such effects may be
      highly relevant during gut colonisation. In the present study, we examined the
      effect of selected NEFA, MAG and sphingosine on the composition of faecal
      microbial communities derived from infants aged 2-5 months during a 24 h
      anaerobic in vitro fermentation. We tested lipid mixtures in the concentration
      range of 0-200 MUm, either based on MC-NEFA (10 : 0 to 14 : 0 and MAG 12 : 0) or
      long-chained NEFA (LC-NEFA; 16 : 0 to 18 : 1 and MAG 16 : 0) with and without
      sphingosine, representing lipid hydrolysis products characteristic for intestinal
      hydrolysis of breast milk lipids. Ion Torrent sequencing of the bacterial 16S
      ribosomal RNA gene revealed that the relative abundance of lactic acid-producing
      genera, including Lactobacillus and Bifidobacterium, was generally increased in
      the presence of 50 MUm or higher concentrations of MC-NEFA. For Bifidobacterium,
      the same effect was also observed in the presence of a mixture containing LC-NEFA
      with sphingosine. On the contrary, the relative abundance of Enterobacteriaceae
      was significantly decreased in the presence of both lipid mixtures. Our findings
      suggest that the high concentration of medium-chained fatty acids in breast milk
      might have functional effects on the establishment of the gut microbiota in early
      life. 

PMID- 25992464
TI  - Monolayer-Mediated Growth of Organic Semiconductor Films with Improved Device
      Performance.
AB  - Increased interest in wearable and smart electronics is driving numerous research
      works on organic electronics. The control of film growth and patterning is of
      great importance when targeting high-performance organic semiconductor devices.
      In this Feature Article, we summarize our recent work focusing on the growth,
      crystallization, and device operation of organic semiconductors intermediated by
      ultrathin organic films (in most cases, only a monolayer). The site-selective
      growth, modified crystallization and morphology, and improved device performance
      of organic semiconductor films are demonstrated with the help of the inducing
      layers, including patterned and uniform Langmuir-Blodgett monolayers, crystalline
      ultrathin organic films, and self-assembled polymer brush films. The introduction
      of the inducing layers could dramatically change the diffusion of the organic
      semiconductors on the surface and the interactions between the active layer with
      the inducing layer, leading to improved aggregation/crystallization behavior and
      device performance. 

PMID- 25992465
TI  - Formal [4+1] annulation reactions in the synthesis of carbocyclic and
      heterocyclic systems.

PMID- 25992466
TI  - Evaluating the climate benefits of CO2-enhanced oil recovery using life cycle
      analysis.
AB  - This study uses life cycle analysis (LCA) to evaluate the greenhouse gas (GHG)
      performance of carbon dioxide (CO2) enhanced oil recovery (EOR) systems. A
      detailed gate-to-gate LCA model of EOR was developed and incorporated into a
      cradle-to-grave boundary with a functional unit of 1 MJ of combusted gasoline.
      The cradle-to-grave model includes two sources of CO2: natural domes and
      anthropogenic (fossil power equipped with carbon capture). A critical parameter
      is the crude recovery ratio, which describes how much crude is recovered for a
      fixed amount of purchased CO2. When CO2 is sourced from a natural dome,
      increasing the crude recovery ratio decreases emissions, the opposite is true for
      anthropogenic CO2. When the CO2 is sourced from a power plant, the electricity
      coproduct is assumed to displace existing power. With anthropogenic CO2,
      increasing the crude recovery ratio reduces the amount of CO2 required, thereby
      reducing the amount of power displaced and the corresponding credit. Only the
      anthropogenic EOR cases result in emissions lower than conventionally produced
      crude. This is not specific to EOR, rather the fact that carbon-intensive
      electricity is being displaced with captured electricity, and the fuel produced
      from that system receives a credit for this displacement.

PMID- 25992467
TI  - Reanalysis of Rate Data for the Reaction CH3 + CH3 -> C2H6 Using Revised Cross
      Sections and a Linearized Second-Order Master Equation.
AB  - Rate coefficients for the CH3 + CH3 reaction, over the temperature range 300-900
      K, have been corrected for errors in the absorption coefficients used in the
      original publication ( Slagle et al., J. Phys. Chem. 1988 , 92 , 2455 - 2462 ).
      These corrections necessitated the development of a detailed model of the B(2)A1'
      (3s)-X(2)A2" transition in CH3 and its validation against both low temperature
      and high temperature experimental absorption cross sections. A master equation
      (ME) model was developed, using a local linearization of the second-order decay,
      which allows the use of standard matrix diagonalization methods for the
      determination of the rate coefficients for CH3 + CH3. The ME model utilized
      inverse Laplace transformation to link the microcanonical rate constants for
      dissociation of C2H6 to the limiting high pressure rate coefficient for
      association, kinfinity(T); it was used to fit the experimental rate coefficients
      using the Levenberg-Marquardt algorithm to minimize chi(2) calculated from the
      differences between experimental and calculated rate coefficients. Parameters for
      both kinfinity(T) and for energy transfer ?DeltaE?down(T) were varied and
      optimized in the fitting procedure. A wide range of experimental data were
      fitted, covering the temperature range 300-2000 K. A high pressure limit of
      kinfinity(T) = 5.76 * 10(-11)(T/298 K)(-0.34) cm(3) molecule(-1) s(-1) was
      obtained, which agrees well with the best available theoretical expression. 

PMID- 25992468
TI  - Utilizing Microchip Capillary Electrophoresis Electrospray Ionization for
      Hydrogen Exchange Mass Spectrometry.
AB  - Hydrogen exchange (HX) mass spectrometry (MS) of complex mixtures requires a
      fast, reproducible, and high peak capacity separation prior to MS detection. The
      current paradigm relies on liquid chromatography (LC) with fast gradients
      performed at low temperatures to minimize back exchange. Unfortunately, under
      these conditions, the efficiency of LC is limited due to resistance to mass
      transfer, reducing the capability to analyze complex samples. Capillary
      electrophoresis (CE), on the other hand, is not limited by resistance to mass
      transfer, enabling very rapid separations that are not adversely affected by low
      temperature. Previously, we have demonstrated an integrated microfluidic device
      coupling CE with electrospray ionization (ESI) capable of very rapid and high
      efficiency separations. In this work, we demonstrate the utility of this
      microchip CE-ESI device for HX MS. High speed CE-ESI of a bovine hemoglobin
      pepsin digestion was performed in 1 min with a peak capacity of 62 versus a
      similar LC separation performed in 7 min with peak capacity of 31. A room
      temperature CE method performed in 1.25 min provided similar deuterium retention
      as an 8.5 min LC method conducted at 0  degrees C. Separation of a complex
      mixture with CE was done with considerably better speed and nearly triple the
      peak capacity than the equivalent separation by LC. Overall, the results indicate
      the potential utility of microchip CE-ESI for HX MS. 

PMID- 25992473
TI  - Gold-catalyzed oxime-oxime rearrangement.
AB  - The gold-catalyzed reaction of pyrrole and indole oximes having a propargyl group
      attached to the nitrogen atom was studied. The selective 6-endo-dig mode of
      cyclization was observed for the terminal alkynes giving rise to the formation of
      pyrazine N-oxides in the presence of a gold catalyst. However, the reaction with
      substituted alkyne transferred the oxime functionality intramolecularly from one
      carbon atom to another via the 7-endo-dig cyclization process. This
      transformation is unprecedented in the literature and is named an oxime-oxime
      rearrangement. 

PMID- 25992469
TI  - Whole-animal imaging and flow cytometric techniques for analysis of antigen
      specific CD8+ T cell responses after nanoparticle vaccination.
AB  - Traditional vaccine adjuvants, such as alum, elicit suboptimal CD8+ T cell
      responses. To address this major challenge in vaccine development, various
      nanoparticle systems have been engineered to mimic features of pathogens to
      improve antigen delivery to draining lymph nodes and increase antigen uptake by
      antigen-presenting cells, leading to new vaccine formulations optimized for
      induction of antigen-specific CD8+ T cell responses. In this article, we describe
      the synthesis of a "pathogen-mimicking" nanoparticle system, termed interbilayer
      crosslinked multilamellar vesicles (ICMVs) that can serve as an effective vaccine
      carrier for co-delivery of subunit antigens and immunostimulatory agents and
      elicitation of potent cytotoxic CD8+ T lymphocyte (CTL) responses. We describe
      methods for characterizing hydrodynamic size and surface charge of vaccine
      nanoparticles with dynamic light scattering and zeta potential analyzer and
      present a confocal microscopy-based procedure to analyze nanoparticle-mediated
      antigen delivery to draining lymph nodes. Furthermore, we show a new
      bioluminescence whole-animal imaging technique utilizing adoptive transfer of
      luciferase-expressing, antigen-specific CD8+ T cells into recipient mice,
      followed by nanoparticle vaccination, which permits non-invasive interrogation of
      expansion and trafficking patterns of CTLs in real time. We also describe
      tetramer staining and flow cytometric analysis of peripheral blood mononuclear
      cells for longitudinal quantification of endogenous T cell responses in mice
      vaccinated with nanoparticles. 

PMID- 25992474
TI  - Isolation of human lymphatic endothelial cells by multi-parameter fluorescence
      activated cell sorting.
AB  - Lymphatic system disorders such as primary lymphedema, lymphatic malformations
      and lymphatic tumors are rare conditions that cause significant morbidity but
      little is known about their biology. Isolating highly pure human lymphatic
      endothelial cells (LECs) from diseased and healthy tissue would facilitate
      studies of the lymphatic endothelium at genetic, molecular and cellular levels.
      It is anticipated that these investigations may reveal targets for new therapies
      that may change the clinical management of these conditions. A protocol
      describing the isolation of human foreskin LECs and lymphatic malformation
      lymphatic endothelial cells (LM LECs) is presented. To obtain a single cell
      suspension tissue was minced and enzymatically treated using dispase II and
      collagenase II. The resulting single cell suspension was then labelled with
      antibodies to cluster of differentiation (CD) markers CD34, CD31, Vascular
      Endothelial Growth Factor-3 (VEGFR-3) and PODOPLANIN. Stained viable cells were
      sorted on a fluorescently activated cell sorter (FACS) to separate the
      CD34(Low)CD31(Pos)VEGFR-3(Pos)PODOPLANIN(Pos) LM LEC population from other
      endothelial and non-endothelial cells. The sorted LM LECs were cultured and
      expanded on fibronectin-coated flasks for further experimental use. 

PMID- 25992475
TI  - Systemic bacterial infection and immune defense phenotypes in Drosophila
      melanogaster.
AB  - The fruit fly Drosophila melanogaster is one of the premier model organisms for
      studying the function and evolution of immune defense. Many aspects of innate
      immunity are conserved between insects and mammals, and since Drosophila can
      readily be genetically and experimentally manipulated, they are powerful for
      studying immune system function and the physiological consequences of disease.
      The procedure demonstrated here allows infection of flies by introduction of
      bacteria directly into the body cavity, bypassing epithelial barriers and more
      passive forms of defense and allowing focus on systemic infection. The procedure
      includes protocols for the measuring rates of host mortality, systemic pathogen
      load, and degree of induction of the host immune system. This infection procedure
      is inexpensive, robust and quantitatively repeatable, and can be used in studies
      of functional genetics, evolutionary life history, and physiology. 

PMID- 25992476
TI  - Sleep-independent offline consolidation of response inhibition during the daytime
      post-training period.
AB  - Appropriate inhibitory response control is associated with goal-directed
      behavior. Sleep accelerates the offline consolidation of acquired motor skills
      that are explicitly predictable; however, the effect of sleep on implicit
      (unpredictable) motor skills remains controversial. We speculated that a key
      component of response inhibition skill differentiates between these skill
      consolidation properties because explicit prediction can minimize the inhibitory
      efforts in a motor skill. We explored the offline skill learning properties of
      response inhibition during sleep and wakefulness using auditory Go and Go/Nogo
      tasks. We attempted to discriminate the possible effects of time elapsed after
      training (12 or 24 h), post-training sleep/wake state (sleep or wakefulness), and
      time of day (nighttime or daytime) in 79 healthy human subjects divided into 6
      groups that underwent various sleep regimens prior to training and retesting. We
      found that delayed response inhibition skill improvement was achieved via a
      simple passage of daytime, regardless of the participants' alertness level. Our
      results suggest that sleep-independent neuroplasticity occurs during the daytime
      and facilitates a delayed learning of response inhibition skill.

PMID- 25992477
TI  - Measure of anxiety-related behaviors and hippocampal BDNF levels associated to
      the amnesic effect induced by MK-801 evaluated in the modified elevated plus-maze
      in rats.
AB  - Non-competitive N-methyl-d-aspartate receptor (NMDA-R) antagonists impair rodent
      cognition. Specifically, MK-801, the most potent NMDA-R antagonist, induces an
      amnesic effect on the modified elevated plus maze (mEPM) learning test in
      rodents, which reflects spatial long-term memory. However, alterations in anxiety
      related behaviors could overlap this amnesic effect. Accumulated evidence
      supports the role of brain-derived neurotrophic factor (BDNF) in learning and
      memory processes and deficits in hippocampal BDNF function, which underlie
      cognitive impairments, have been extensively reported. Therefore, we investigated
      if changes in anxiety-related behaviors and hippocampal BDNF levels are related
      with the amnesic effect induced by MK-801 in the mEPM.Transfer latency (TL) as an
      index of spatial memory in the mEPM was used. TL1 was evaluated 30 min after
      saline/MK-801 injection (day 1, acquisition session) while learning/memory
      performance was measured 24 h later at TL2 (day 2, retention session). Also at
      TL2, two other experimental groups were added to measure the anxiety-related
      behaviors using the classic EPM and BDNF protein levels by ELISA. To evaluate if
      amnesia endures, an additional session was recorded on day 3 (TL3) and BDNF
      levels were measured.While TL1 was not significantly modified by MK-801, TL2 was
      increased compared to the control group indicating an amnesic effect. This effect
      was not mimicked by anxiety-related behaviors and it was associated to a
      significant attenuation of BDNF levels. During the third post-training day, the
      cognitive performance of MK-801-treated animals was improved and an increased
      BDNF protein expression in the hippocampus accompanied this change

PMID- 25992478
TI  - Stress responses to chemical alarm cues in Nile tilapia.
AB  - In predator-prey encounters between fish in which there is physical trauma to the
      epidermis of the prey, some species release chemical alarm cues into the water.
      Fish of the same species may perceive these cues and display antipredator
      behavior. Physiological adjustments may also be needed to deal with this adverse
      situation. To date, little attention has been devoted to the physiological
      adjustments that may co-occur with defensive responses. We have characterized the
      alarm cue-induced antipredator behaviors and stress responses in Nile tilapia,
      Oreochromis niloticus. Specifically, chemical alarm cues decreased feeding
      activity and induced dashing reactions while also inducing the primary stress
      responses, increased ventilation rate and cortisol level. Glucose levels remained
      unaltered, leading to the conclusion that secondary stress responses were not
      induced in this study. Nile tilapia stress responses to chemical alarm cues
      differed from those reported for other fish species, and may depend on the nature
      of the stimulus or on the species studied. Future studies should ideally aim to
      identify patterns in stress response to chemical alarm cues in fishes and resolve
      this question.

PMID- 25992479
TI  - Photoperiodic modulation of voluntary ethanol intake in C57BL/6 mice.
AB  - Seasonal and geographic variations in light exposure influence human mood and
      behavior, including alcohol consumption. Similarly, manipulation of the
      environmental lighting regimen modulates voluntary ethanol intake in experimental
      animals. Nevertheless, previous studies in rats and hamsters have been somewhat
      inconsistent, and little is known concerning such effects in mice. In the present
      study, we maintained male C57Bl/6 mice in running-wheel cages under either short-
      or long-photoperiod light-dark cycles (LD 6:18 vs. LD 18:6); subsequently, the
      same animals were maintained under short or long "skeleton photoperiods",
      consisting of two daily 15-min light pulses signaling dusk and dawn (SP 6:18 vs.
      SP 18:6). Running wheels were locked mechanically for half the animals under each
      photoperiod. Analysis of running wheel patterns showed that mice displayed stable
      circadian adaptation to both standard LD cycles and skeleton photoperiods. Mice
      consumed more ethanol and less water, and thus showed higher ethanol preference,
      under LD 6:18 and SP 6:18 relative to the corresponding long-photoperiod
      regimens. While running-wheel access increased water intake, ethanol intake was
      unaffected by this manipulation. These effects are consistent with previous
      studies showing that short photoperiods or constant darkness increases ethanol
      intake in rodents. Further, the similarity of the effects of complete and
      skeleton photoperiods suggests that these effects are mediated by photoperiod
      induced alterations in the circadian entrainment pattern, rather than by light
      exposure per se. 

PMID- 25992480
TI  - Individual differences in anticipatory activity to food rewards predict cue
      induced appetitive 50-kHz calls in rats.
AB  - Reward-related stimuli come to acquire incentive salience through Pavlovian
      learning and become capable of controlling reward-oriented behaviors. Here, we
      examined individual differences in anticipatory activity elicited by reward
      related cues as indicative of how animals attribute incentive salience to
      otherwise neutral stimuli. Since adult rats can signal incentive motivation
      states through ultrasonic vocalizations (USVs) at around 50-kHz, such calls were
      recorded in food-deprived rats trained to associate cues with food rewards, which
      were subsequently devalued by satiation.We found that the extent to which animals
      developed conditioned anticipatory activity to food cues while food deprived
      determined the level of cue-induced appetitive USVs while sated. Re-exposure to
      reward cues after a free-testing period reinstated USVs, invigorated reward
      seeking and consumption, and again, increases in calling occurred only in animals
      with high levels of cue-induced anticipatory activity. Reward-experienced rats
      systemically challenged with the catecholamine agonist amphetamine or with the
      dopamine receptor antagonist flupenthixol showed attenuated responses to these
      drugs, especially for USVs and in subjects with high levels of cue-induced
      anticipatory activity. Our results suggest that individuals prone to attribute
      incentive salience to reward cues showed heightened reward-induced USVs which
      were reliably expressed over time and persisted despite physiological needs being
      fulfilled. Also, prone subjects seemed to undergo particular adaptations in their
      dopaminergic system related with incentive learning. Our findings may have
      translational relevance in preclinical research modeling compulsive disorders,
      which may be due to excessive attribution of incentive salience to reward cues,
      such as overeating, pathological gambling, and drug addiction.

PMID- 25992483
TI  - Salt induced reduction of lysozyme adsorption at charged interfaces.
AB  - A study of lysozyme adsorption below a behenic acid membrane and at the solid
      liquid interface between aqueous lysozyme solution and a silicon wafer in the
      presence of sodium chloride is presented. The salt concentration was varied
      between 1 mmol L(-1) and 1000 mmol L(-1). X-ray reflectivity data show a clear
      dependence of the protein adsorption on the salt concentration. Increasing salt
      concentrations result in a decreased protein adsorption at the interface until a
      complete suppression at high concentrations is reached. This effect can be
      attributed to a reduced attractive electrostatic interaction between the
      positively charged proteins and negatively charged surfaces by charge screening.
      The measurements at the solid-liquid interfaces show a transition from unoriented
      order of lysozyme in the adsorbed film to an oriented order with the short
      protein axis perpendicular to the solid-liquid interface with rising salt
      concentration.

PMID- 25992481
TI  - SIRT1 protects rat lung tissue against severe burn-induced remote ALI by
      attenuating the apoptosis of PMVECs via p38 MAPK signaling.
AB  - Silent information regulator type-1 (SIRT1) has been reported to be involved in
      the cardiopulmonary protection. However, its role in the pathogenesis of burn
      induced remote acute lung injury (ALI) is currently unknown. The present study
      aims to investigate the role of SIRT1 in burn-induced remote ALI and the involved
      signaling pathway. We observed that SIRT1 expression in rat lung tissue after
      burn injury appeared an increasing trend after a short period of suppression. The
      upregulation of SIRT1 stimulated by resveratrol exhibited remission of
      histopathologic changes, reduction of cell apoptosis, and downregulation of pro
      inflammatory cytokines in rat pulmonary tissues suffering from severe burn. We
      next used primary pulmonary microvascular endothelial cells (PMVECs) challenged
      by burn serum (BS) to simulate in vivo rat lung tissue after burn injury, and
      found that BS significantly suppressed SIRT1 expression, increased cell
      apoptosis, and activated p38 MAPK signaling. The use of resveratrol reversed
      these effects, while knockdown of SIRT1 by shRNA further augmented BS-induced
      increase of cell apoptosis and activation of p38 MAPK. Taken together, these
      results indicate that SIRT1 might protect lung tissue against burn-induced remote
      ALI by attenuating PMVEC apoptosis via p38 MAPK signaling, suggesting its
      potential therapeutic effects on the treatment of ALI. 

PMID- 25992482
TI  - Effects and Mechanism of Atmospheric-Pressure Dielectric Barrier Discharge Cold
      Plasma on Lactate Dehydrogenase (LDH) Enzyme.
AB  - Proteins are carriers of biological functions and the effects of atmospheric
      pressure non-thermal plasmas on proteins are important to applications such as
      sterilization and plasma-induced apoptosis of cancer cells. Herein, we report our
      detailed investigation of the effects of helium-oxygen non-thermal dielectric
      barrier discharge (DBD) plasmas on the inactivation of lactate dehydrogenase
      (LDH) enzyme solutions. Circular dichroism (CD) and dynamic light scattering
      (DLS) indicate that the loss of activity stems from plasma-induced modification
      of the secondary molecular structure as well as polymerization of the peptide
      chains. Raising the treatment intensity leads to a reduced alpha-helix content,
      increase in the percentage of the beta-sheet regions and random sequence, as well
      as gradually decreasing LDH activity. However, the structure of the LDH plasma
      treated for 300 seconds exhibits a recovery trend after storage for 24 h and its
      activity also increases slightly. By comparing direct and indirect plasma
      treatments, plasma-induced LDH inactivation can be attributed to reactive species
      (RS) in the plasma, especially ones with a long lifetime including hydrogen
      peroxide, ozone, and nitrate ion which play the major role in the alteration of
      the macromolecular structure and molecular diameter in lieu of heat, UV
      radiation, and charged particles.

PMID- 25992484
TI  - Nanostructured 2D Diporphyrin Honeycomb Film: Photoelectrochemistry,
      Photodegradation, and Antibacterial Activity.
AB  - Surface patterns of well-defined nanostructures play important roles in
      fabrication of optoelectronic devices and applications in catalysis and biology.
      In this paper, the diporphyrin honeycomb film, composed of titanium dioxide,
      protoporphyrin IX, and hemin (TiO2/PPIX/Hem), was synthesized using a dewetting
      technique with the well-defined polystyrene (PS) monolayer as a template. The
      TiO2/PPIX/Hem honeycomb film exhibited a higher photoelectrochemical response
      than that of TiO2 or TiO2/PPIX, which implied a high photoelectric conversion
      efficiency and a synergistic effect between the two kinds of porphyrins. The
      TiO2/PPIX/Hem honeycomb film was also a good photosensitizer due to its ability
      to generate singlet oxygen ((1)O2) under irradiation by visible light. This led
      to the use of diporphyrin TiO2/PPIX/Hem honeycomb film for the photocatalytic
      inactivation of bacteria. In addition, the photocatalytic activities of other
      metal-diporphyrin-based honeycomb films, such as TiO2/MnPPIX/Hem,
      TiO2/CoPPIX/Hem, TiO2/NiPPIX/Hem, TiO2/CuPPIX/Hem, and TiO2/ZnPPIX/Hem, were
      investigated. The result demonstrated that the photoelectric properties of
      diporphyrin-based film could be effectively enhanced by further coupling of
      porphyrin with metal ions. Such enhanced performance of diporphyrin compounds
      opened a new way for potential applications in various photoelectrochemical
      devices and medical fields. 

PMID- 25992486
TI  - Two polymorphisms in the Cx40 promoter are associated with hypertension and left
      ventricular hypertrophy preferentially in men.
AB  - BACKGROUND: Lack of connexin40, a gap junction protein expressed in endothelial
      and renin-producing cells, results in hypertension and cardiac hypertrophy in
      mice due to unleashed renin production caused by disruption of the pressure
      induced feedback inhibition. We analysed human GJA5 consisting of two exons
      (exon1A or 1B and exon2) in a selected cohort identified by a single nucleotide
      polymorphism (SNP) in the GJA5 intron for polymorphisms and putative association
      with hypertension and left ventricular hypertrophy (LVH). METHODS: Individuals
      carrying a SNP in the intron of GJA5 (rs791295) were selected from the
      MONICA/KORA cohort (n = 1677) and searched for GJA5 polymorphisms. We accessed
      DNA of 178 probands, of which 26 suffered from LVH, 112 were hypertensive and 29
      normotensive (unknown: 11). RESULTS: Sequencing of the GJA5 coding region did not
      reveal alterations suggesting the expression of functional connexin40 in all
      probands. Sequencing of the upstream region of transcript 1A including exon1A
      revealed two previously described linked SNPs (rs35594137 -44G>A; rs11552588 +
      71A>G) at an increased frequency. Moreover, the rare genotype was significantly
      associated with hypertension and LVH with a preponderance in men. Functional
      analysis in a reporter gene assay verified promoter activity, however, it was
      unchanged by the identified SNPs after expressing respective reporter constructs
      in HeLa and human endothelial cells. CONCLUSION: We suggest to consider the 
      44G>A SNP upstream of the connexin40 transcript 1A indeed as a risk factor for
      hypertension in men. However, the underlying mechanisms remain unclear but animal
      data suggest that renin-producing cells may be involved and contribute to
      hypertension.

PMID- 25992485
TI  - The role of cyclooxygenase-2, interleukin-1beta and fibroblast growth factor-2 in
      the activation of matrix metalloproteinase-1 in sheared-chondrocytes and
      articular cartilage.
AB  - MMP-1 expression is detected in fluid shear stress (20 dyn/cm(2))-activated and
      osteoarthritic human chondrocytes, however, the precise mechanisms underlying
      shear-induced MMP-1 synthesis remain unknown. Using primary chondrocytes and T/C
      28a2 chondrocytic cells as model systems, we report that prolonged application of
      high fluid shear to human chondrocytes induced the synthesis of cyclooxygenase-2
      (COX-2), interleukin-1beta (IL-1beta) and fibroblast growth factor-2 (FGF-2),
      which led to a marked increase in MMP-1 expression. IL-1beta, COX-2-dependent
      PGE2 activated the PI3-K/AKT and p38 signaling pathways, which were in turn
      responsible for MMP-1 synthesis via NF-kappaB- and c-Jun-transactivating
      pathways. Prolonged shear stress exposure (>12 h) induced 15-Deoxy-Delta(12,14)
      prostaglandin J2 (15d-PGJ2) synthesis. Although 15d-PGJ2 suppressed PI3-K/AKT and
      p38 signaling pathways, it stimulated MMP-1 expression via activating heme
      oxygenase 1 (HO-1). The critical role of COX-2 in regulating MMP-1 expression in
      articular cartilage in vivo was demonstrated using COX-2(+/-) transgenic mice in
      the absence or presence of rofecoxib oral administration. These findings provide
      novel insights for developing therapeutic strategies to combat OA.

PMID- 25992487
TI  - Differences in 24-h blood pressure profile of Japanese hypertensive patients
      under ARB treatment.
AB  - Blood pressure (BP) control throughout the entire day is recommended for
      cardiovascular protection. Angiotensin-II receptor blockers (ARBs) are widely
      used in hypertensive patients because of beneficial class effects. It is
      uncertain, however, whether are there any differences in 24-h BP profiles among
      ARBs. We examined ambulatory blood pressure monitoring (ABPM) among 211 Japanese
      hypertensive patients (age, 69.4 +/- 9.6 years; female, 59.2%) under treatment
      with five different ARBs. Patients were divided into five groups according to
      ARBs prescribed. Patient backgrounds were almost identical in all the groups and
      there were no differences in office, 24-h and daytime BP; however, nighttime BP
      with olmesartan was significantly lower than with other ARBs. Office BPs with
      candesartan and telmisartan, but not other ARBs, correlated well with 24-h BP (p
      < 0.01). Also, there were higher correlations between daytime and nighttime BP
      with candesartan and telmisartan. In all patients, pulse pressure with office BP
      was significantly correlated with ambulatory arterial stiffness index (p = 0.001)
      and fluctuation of systolic BP on ABPM (p = 0.002). In conclusion, different ARB
      treatments produced meaningful differences in 24-h profiles. 

PMID- 25992488
TI  - Effects of a selective aldosterone blocker and thiazide-type diuretic on blood
      pressure and organ damage in hypertensive patients.
AB  - The aim of the present study was to compare the effects of the aldosterone
      blocker eplerenone and thiazide-like diuretic indapamide on blood pressure (BP)
      and target organs with reference to salt intake in hypertensive outpatients.
      Twenty hypertensive patients (nine women and 11 men, mean age 71 +/- 13 years)
      with inadequate BP control despite taking calcium channel blockers (CCBs) and
      angiotensin II receptor blockers (ARBs) were administered eplerenone (50 mg/day)
      or indapamide (1 mg/day) for 3 months each in a randomized crossover manner. Salt
      intake, BP and indices of organ damage were assessed at baseline and at the end
      of each treatment period. Eplerenone and indapamide were similarly effective in
      lowering office and home BPs. Both the treatments significantly reduced the
      estimated glomerular filtration rate (eGFR) and increased serum uric acid levels.
      The treatment with eplerenone significantly increased serum potassium levels,
      whereas the treatment with indapamide significantly decreased them. The treatment
      with eplerenone significantly decreased pulse wave velocity and urinary 8
      hydroxydeoxyguanosine levels. These changes were not significantly affected by
      the treatment with indapamide. In conclusion, eplerenone and indapamide were
      similarly effective in lowering office and home BPs in hypertensive patients
      treated with CCBs and ARBs. Eplerenone may exert more favorable effects on
      arterial stiffness and oxidative stress. 

PMID- 25992489
TI  - A prospective study of frequency and characteristics of cough during ACE
      inhibitor treatment.
AB  - Angiotensin converting enzyme (ACE) inhibitors are reportedly effective, and
      positively indicated in patients with chronic heart failure with decreased
      contractility, after myocardial infarction, after cerebrovascular disorders, and
      in those with chronic kidney disease. However, the biggest challenge to
      continuous use of ACE inhibitors is the adverse reaction of cough. Accordingly,
      in the present study, we investigated the present state and characteristics of
      ACE inhibitor-induced cough in patients with essential hypertension currently
      being treated with an ACE inhibitor for an average of 18 months, who could be
      regularly checked for cough. Subjects in this study were 176 patients overall
      (mean age 67 +/- 11 years old), 90 men and 86 women. The adverse reaction of
      cough was observed in 20% of patients, and more frequently in women than in men.
      However, in 26 of the patients with cough, the cough either resolved naturally or
      completely disappeared while the treatment continued, after which patients could
      continue taking the medication. Specifically, ACE inhibitor treatment was
      eventually discontinued due to cough in 5.1% of patients. Cough occurred less
      frequently with concomitant calcium antagonists or diuretics than with ACE
      inhibitor monotherapy. Cough as an adverse reaction occurred at a low frequency
      when medication was taken at bedtime. We considered a number of measures to
      counteract cough, then in addition to starting the ACE inhibitor treatment as
      early as possible, it is important to devise ways for the ACE inhibitor treatment
      to be continued for as long as possible, through the adept use of these measures.

PMID- 25992490
TI  - Association between homocysteine and incidence of ischemic stroke in subjects
      with essential hypertension: a matched case-control study.
AB  - BACKGROUND: To assess the association between total plasma homocysteine (tHcy)
      and ischemic stroke (IS) in hypertensive subjects in a matched case-control
      study. METHODS: This is a 1:2 matched and population-based case-control study,
      all of the participants were recruited from the 60 communities in Shenzhen,
      China. Demographic and socioeconomic characteristics, medical records, lifestyle
      risk factors and other clinical characteristics were obtained from all of the
      subjects. The association between tHcy and incidence of IS was analyzed by using
      conditional logistic regression models. RESULTS: The median values of plasma tHcy
      were significantly higher in IS subjects than in non-IS subjects, especially in
      women. After adjusted for the confounding factors in Model 2, compared with the
      lowest quartile of tHcy, the odds ratios (ORs) and 95% CIs of the highest
      quartile of tHcy for IS were 0.83 (0.36-1.90) in men, 4.51 (1.29-15.7) in women
      and 1.31 (0.70-2.47) in the total subjects; the ORs and 95% CIs for IS per 5
      MUmol/L increase in homocysteine were 1.11 (0.99-1.22), 1.25 (1.03-1.58) and 1.15
      (1.01-1.28) in men, women and total subjects, respectively. We observed
      significant associations in crude model, Model 1 and Model 2 in women for the
      comparison of tHcy >= 15 MUmol/L versus < 15 MUmol/L. Interaction analysis showed
      that the association of tHcy with IS was significant in women (p-interaction =
      0.04). CONCLUSION: This matched case-control study indicates that tHcy may
      increase the susceptibility to IS in essential hypertension subjects, especially
      in women. Further large prospective cohort studies are needed to confirm our
      findings.

PMID- 25992491
TI  - Investigating information-processing performance of different command team
      structures in the NATO Problem Space.
AB  - The structure of command teams is a significant factor on their communications
      and ability to process, and act upon, information. The NATO Problem Space was
      used in this study to represent three of the main dimensions in the battle-space
      environment: familiarity, rate of change, and strength of information position.
      Results show that the five common team structures (chain, Y, circle, wheel and
      all-connected) did not generally perform as predicted in team literature.
      Findings suggest that under dynamic and highly variable conditions, high levels
      of synchronisation and trust should be present. On the other hand,
      synchronisation and trust are less important in hierarchical, highly centralised
      structures, because team members are more willing to accept the authority of a
      single leader and this tight control ensures that these teams can perform well as
      long as the Problem Space is familiar, information is explicit and the
      environment does not change. Practitioner Summary: Some types of team structures
      are better suited to particular constraints of the battle-space than others. This
      research has shown that the much touted all-connected structure is often the
      worst performing structure and that the traditional hierarchy of command and
      control has much merit in the digital information age.

PMID- 25992492
TI  - Two-photon polymerization microfabrication of hydrogels: an advanced 3D printing
      technology for tissue engineering and drug delivery.
AB  - 3D printing technology has attracted much attention due to its high potential in
      scientific and industrial applications. As an outstanding 3D printing technology,
      two-photon polymerization (TPP) microfabrication has been applied in the fields
      of micro/nanophotonics, micro-electromechanical systems, microfluidics,
      biomedical implants and microdevices. In particular, TPP microfabrication is very
      useful in tissue engineering and drug delivery due to its powerful fabrication
      capability for precise microstructures with high spatial resolution on both the
      microscopic and the nanometric scale. The design and fabrication of 3D hydrogels
      widely used in tissue engineering and drug delivery has been an important
      research area of TPP microfabrication. The resolution is a key parameter for 3D
      hydrogels to simulate the native 3D environment in which the cells reside and the
      drug is controlled to release with optimal temporal and spatial distribution in
      vitro and in vivo. The resolution of 3D hydrogels largely depends on the
      efficiency of TPP initiators. In this paper, we will review the widely used
      photoresists, the development of TPP photoinitiators, the strategies for
      improving the resolution and the microfabrication of 3D hydrogels. 

PMID- 25992493
TI  - Symptomatic Accessory Medial Meniscus Associated With Popliteal Pterygium
      Syndrome.
AB  - BACKGROUND: Anomalies of the meniscus are uncommon. These anomalous formations
      have been predominately described in the lateral compartment of the knee.
      Congenital abnormalities of the medial meniscus are rare. METHODS: Chart and
      radiographic review of a single patient with a symptomatic congenital abnormality
      of the medial meniscus. RESULTS: The patient was a 5-year-old boy with popliteal
      pterygium who developed painful snapping in the medial knee after anterior
      hemiepiphyseodesis to improve his knee extension. The patient had achieved full
      knee extension from a preoperative 45-degree flexion contracture. The newly
      developed snapping was attributed to the hemiepiphyseodesis implants. After
      implant removal, the snapping persisted and was localized at the medial joint
      line. Through an arthrotomy, a medial meniscus abnormality was identified and
      excised with resolution of symptoms. CONCLUSIONS: This report describes a
      symptomatic congenital abnormality of the medial meniscus in a child with
      popliteal pterygium. The patient was treated with excision of the anomalous
      structure with complete resolution of the symptoms. This is the first report of
      an intra-articular knee anomaly associated with popliteal pterygium syndrome.

PMID- 25992494
TI  - Intravenous immunoglobulin for presumed viral myocarditis in children and adults.
AB  - BACKGROUND: This is an update of a previous review. Case reports and case series
      have described dramatic responses to intravenous immunoglobulin (IVIG) in people
      with presumed viral myocarditis, and its administration has become commonplace.
      OBJECTIVES: The primary objective of this review was to compare transplant-free
      survival of adults and children with presumed viral myocarditis treated with IVIG
      versus those who did not receive IVIG. A secondary objective was to determine if
      a group of patients with presumed viral myocarditis could be identified (on the
      basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function
      at presentation, virological results or the presence or absence of histological
      evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was
      performed) who would be the most likely to benefit from IVIG. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013,
      Issue 12 of 12), the Database of Abstracts of Reviews of Effects (DARE) (2013,
      Issue 4 of 4), MEDLINE (Ovid, 1946 to January Week 3 2014), EMBASE (Ovid, 1980 to
      Week 4 2014), the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL) EBSCO, Web of Science (Thomson Reuters, 1970 to 24 January 2014), the
      Latin American and Caribbean Health Science Information Database (LILACS) (1982
      to 30 January 2014), trials registries and conference proceedings. We contacted
      authors of trials and checked reference lists of relevant papers. We applied no
      language restrictions. SELECTION CRITERIA: We included studies if (1)
      participants had a clinical diagnosis of acute myocarditis with a left
      ventricular ejection fraction (LVEF) <= 0.45, left ventricular end-diastolic
      diameter (LVEDD) > 2 standard deviations (SDs) above the norm or a shortening
      fraction (SF) > 2 SDs below the mean with duration of cardiac symptoms < 6
      months; (2) participants had no evidence of non-infectious or bacterial cardiac
      disease; and (3) participants were randomly assigned to receive at least 1 g/kg
      of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had
      received immunosuppression before outcome assessment; or (2) onset of myocarditis
      was reported to occur < 6 months post partum. DATA COLLECTION AND ANALYSIS: Two
      review authors screened searches and extracted data independently. We assessed
      quality using the 'Risk of bias' tool. Meta-analysis was not possible because
      only two relevant studies were found, and researchers analysed markedly different
      populations. MAIN RESULTS: In this update, review authors added one study to the
      study from the original review. The first relevant study involved 62 adults with
      recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an
      equivalent volume of 0.1% albumin in a blinded fashion. The overall risk of bias
      was unclear. The incidence of death or the requirement for cardiac transplant or
      placement of a left ventricular assist device was low in both groups (odds ratio
      (OR) for event-free survival 0.52, 95% confidence interval (CI) 0.12 to 2.30).
      Follow-up at six months and at 12 months showed equivalent improvement in LVEF
      (mean difference (MD) 0.00, 95% CI -0.07 to 0.07 at six months; MD 0.01, 95% CI 
      0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen
      consumption was equivalent in the two groups at 12 months (MD -0.80, 95% CI -4.57
      to 2.97). Infusion-related side effects were more common in the treated group,
      but all were reported to be mild (OR 30.16, 95% CI 1.69 to 539.42).The second
      study added at this update included 83 children in India with suspected viral
      encephalitis and myocarditis. The overall risk of bias was high. The odds ratio
      for event-free survival was 7.39 (95% CI 0.91 to 59.86). Follow-up occurred only
      until hospital discharge, and LVEF was 49.5% in the treated group versus 35.9% in
      the placebo group (risk difference 13.6%, 95% CI 5.1 to 22.1%; P value = 0.001).
      AUTHORS' CONCLUSIONS: Evidence from one trial does not support the use of IVIG
      for the treatment of adults with presumed viral myocarditis. The only paediatric
      trial had high risk of bias but suggested that benefit may be seen in the select
      group of children beyond the neonatal period who have viral encephalitis with
      myocarditis. Until higher-quality studies have demonstrated benefit in a
      particular group of patients, IVIG for presumed viral myocarditis should not be
      provided as routine practice in any situation. Further studies of the
      pathophysiology of myocarditis would lead to improved diagnostic criteria, which
      would facilitate future research.

PMID- 25992495
TI  - Assessment of social cognition in non-human primates using a network of
      computerized automated learning device (ALDM) test systems.
AB  - Fagot & Paleressompoulle(1) and Fagot & Bonte(2) have published an automated
      learning device (ALDM) for the study of cognitive abilities of monkeys maintained
      in semi-free ranging conditions. Data accumulated during the last five years have
      consistently demonstrated the efficiency of this protocol to investigate
      individual/physical cognition in monkeys, and have further shown that this
      procedure reduces stress level during animal testing(3). This paper demonstrates
      that networks of ALDM can also be used to investigate different facets of social
      cognition and in-group expressed behaviors in monkeys, and describes three
      illustrative protocols developed for that purpose. The first study demonstrates
      how ethological assessments of social behavior and computerized assessments of
      cognitive performance could be integrated to investigate the effects of socially
      exhibited moods on the cognitive performance of individuals. The second study
      shows that batteries of ALDM running in parallel can provide unique information
      on the influence of the presence of others on task performance. Finally, the last
      study shows that networks of ALDM test units can also be used to study issues
      related to social transmission and cultural evolution. Combined together, these
      three studies demonstrate clearly that ALDM testing is a highly promising
      experimental tool for bridging the gap in the animal literature between research
      on individual cognition and research on social cognition. 

PMID- 25992496
TI  - Physical models of the foetus created using magnetic resonance imaging, computed
      tomography, and ultrasound data: history, description, and potential uses.

PMID- 25992497
TI  - [Factors associated with menopausal symptoms in women from a metropolitan region
      in Southeastern Brazil: a population-based household survey].
AB  - PURPOSE: To determine the average age at the onset of menopause and to
      investigate menopausal symptoms in women in a metropolitan region in Southeastern
      Brazil. METHODS: A descriptive, exploratory, cross-sectional study was conducted
      with 749 women (a population-based household survey). The dependent variable was
      the intensity of menopausal symptoms assessed by th Menopause Rating Scale (MRS).
      The independent variables were sociodemographic data, health-related habits and
      problems, self-perception of health, and gynecological background. Statistical
      analysis was carried out by the chi2 test and Poisson regression using the
      backward selection criteria. RESULTS: The mean age of the women was 52.5 (+/-
      4.4) years. With regard to menopausal status, 16% were premenopausal, 16%
      perimenopausal and 68% postmenopausal. The mean age at the onset of menopause was
      46.5 (+/- 5.8) years. The intensity of menopausal symptoms was defined according
      to the median MRS score and was considered severe for values above 8.
      Depression/anxiety (PR = 1.8; 95%CI 1.5-2.2; p < 0.01), rheumatic diseases (PR
      1.5; 95%CI 1.2-1.7; p < 0.01), self-perception of health as fair/poor/very poor
      (PR 1.4; 95% CI 1.2-1.7; p < 0.01), history of abortion (PR 1.3; 95%CI 1.1-1.4; p
      < 0.01), current or previous treatment for menopausal symptoms (PR 1.2; 95%CI 1.1
      1.4; p < 0.01), peri- or postmenopausal status (PR 1.4; 95%CI 1.1-1.7; p < 0.01),
      number of normal deliveries > 1 (PR 1.2; 95%CI 1.02-1.4; p < 0.01) and asthma (PR
      1.2; 95%CI 1.01-1.4; p < 0.01) were associated with more severe menopausal
      symptoms. Older age (PR 0.96; 95%CI 0.96-0.97; p < 0.01) was associated with less
      severe symptoms. CONCLUSION: The severity of menopausal symptoms was related to a
      wild range of factors, especially presence of chronic diseases, a larger number
      of pregnancies, use of hormone therapy, and worse self-rated health. A better
      understanding of these factors can help to reduce the impact of symptoms on
      quality of life, and to identify groups of women who are likely to need more care
      during and beyond menopause.

PMID- 25992498
TI  - [Pregnancy aspects related to intracranial hemorrhage in newborns of very low
      weight in South Brazil].
AB  - PURPOSE: To analyze the relationship between route of delivery and other aspects
      of pregnancy and the occurrence of intracranial hemorrhage in newborns of very
      low weight at a teaching hospital in South Brazil. METHODS: A case-control study
      was conducted. Medical records of all patients who were born weighing <= 1,500 g
      and who were submitted to transfontanellar ultrasonography were analyzed from
      January 2011 to September 2014. The cases were newborns with diagnosis of
      intracranial hemorrhage, while newborns with regular exams were used as controls.
      Differences between groups were analyzed by the Student t test and by chi2 or
      Fisher exact tests, and association was determined using the odds ratio with a
      95% confidence interval and alpha = 5%. RESULTS: A total of 222 newborns with
      birth weight <= 1,500 g were recorded; of these, 113 were submitted to
      transfontanellar ultrasonography and were included in the study. Sixty-nine
      (61.1%) newborns were diagnosed with intracranial hemorrhage (cases) and 44
      (38.9%) showed no abnormal results (controls). Most cases had grade I hemorrhage
      (96.8%) originating from the germinative matrix (95.7%). The predominant route of
      delivery was caesarean section (81.2% of the cases and 72.7% of the controls).
      Five deaths were recorded (3 cases and 2 controls). Gestational age ranged from
      24 to 37 weeks. Median birth weight was 1,205 g (range: 675-1,500 g). The median
      time of hospitalization was 52 days, ranging from 5 to 163 days. CONCLUSION:
      Grade I intracranial hemorrhage from the germinative matrix was the most
      frequent. No differences were found between cases and controls for the variables
      studied. The small number of infants submitted to transfontanellar
      ultrasonography limited the sample size and the results of the study.

PMID- 25992499
TI  - Factors associated with postpartum weight retention in a Brazilian cohort.
AB  - PURPOSE: To identify the factors associated with weight retention after
      pregnancy. METHODS: A cohort study was performed with 145 women receiving
      maternity care at a hospital in Caxias do Sul, Rio Grande do Sul, Brazil, aged 19
      to 45 years, between weeks 38 and 42 of pregnancy. The patients were evaluated at
      one month, three months, and six months after delivery. Student's t-test or one
      way analysis of variance (ANOVA) was used to compare groups, as indicated;
      correlations were assessed with Pearson's and Spearman's tests, as indicated; to
      identify and evaluate confounders independently associated with total weight
      loss, a multivariate linear regression analysis was performed and statistical
      significance was set at p <= 0.05. RESULTS: There was a significant positive
      association between total weight gain - and a negative association with physical
      exercise during pregnancy - with total weight loss. Higher parity, inter
      pregnancy interval, calorie intake, pre-pregnancy body mass index (BMI), weight
      gain related to pre-pregnancy BMI, presence and severity of depression, and lack
      of exclusive breastfeeding were directly associated with lower weight loss. Among
      nominal variables, level of education and marital status were significantly
      associated with total weight loss. CONCLUSION: In the present study, lower weight
      retention in the postpartum period was associated with higher educational
      attainment and with being married. Normal or below-normal pre-pregnancy BMI,
      physical activity and adequate weight gain during pregnancy, lower parity,
      exclusive breastfeeding for a longer period, appropriate or low calorie intake,
      and absence of depression were also determinants of reduced weight retention.

PMID- 25992501
TI  - [Prevalence of cervical infection by human papillomavirus and cervical
      intraepithelial neoplasia in HIV-positive and negative women].
AB  - PURPOSE: To conduct a comparative study between two groups of women (HIV positive
      and negative) analyzing: the prevalence of cervical intraepithelial neoplasia
      (CIN) and cervical HPV infection; viral risk and relationship with development of
      CIN; and sociodemographic and behavioral parameters that influence cervical HPV
      infection and the development of CIN. METHODS: A cross-sectional study in which
      202 HIV-positive women and 164 HIV-negative women were analyzed to assess the
      prevalence of CIN and 171 HIV-positive women and 160 HIV-negative women were
      analyzed to assess the prevalence of cervical HPV infection. The following
      procedures were performed on the occasion of each medical visit: collection of
      cervical samples for cytology and polymerase chain reaction (PCR) to detect HPV
      DNA; colposcopy; standardized questionnaire to collect demographic and behavioral
      data; and biopsy of all colposcopic changes. Histopathology was the gold standard
      for the diagnosis of CIN. RESULTS: The prevalence of CIN was 2.4 and 15.3%
      (p<0.001) and the prevalence of cervical HPV infection was 37.1 and 55.5%
      (p=0.002), respectively, among HIV-negative and -positive women. HIV-positive
      women had a higher risk of HPV infection (35.7 and 23.6%) (p=0.02). HPV 16 was
      the most prevalent virus type, occurring in 11.3 and 10.2% of HIV-positive and
      negative women and was also more prevalent among women presenting CIN in both
      groups. Factors associated with the development of CIN were: HIV infection
      (HT=4.64; 95%CI 2.23-9.65), age (HT=0.95; 95%CI 0.93-0.98 for each year of life)
      and marital status (HT=0.49; 95%CI 0.30-0.80). Associated factors for HPV
      infection were: HIV presence (HT=2.72; 95%CI 1.77-4.17), greater number of sexual
      partners (HT=1.87; 95%CI 1.23-2.84), age (HT=0.97; 95%CI 0.95-0.99 for each year
      of life) and marital status (HT=0.65; 95%CI 0.42-1.0 for stable union/widows).
      CONCLUSION: The prevalence of CIN and cervical HPV infection was higher in HIV
      positive women, who also presented a higher risk of HPV infections and multiple
      viral types. Type 16 was predominant in both groups and in women with CIN. Older
      women and women with stable union/widows were less likely to acquire cervical HPV
      infection and CIN.

PMID- 25992500
TI  - [Podocyturia in pregnant women with chronic hypertension may predict kidney
      injury?].
AB  - PURPOSE: To evaluate the presence of podocyturia in chronic hypertensive pregnant
      women in the third trimester of pregnancy and its possible association with renal
      disease. METHODS: This was an observational study of a convenience sample of 38
      chronic hypertensive pregnant women. The podocytes were labeled by the indirect
      immunofluorescence technique with anti-podocin and diamidino-phenylindole (DAPI).
      The count was made on 30 random fields analyzed and corrected according to
      urinary creatinine (podocytes/mg creatinine). The patients were assigned to two
      groups: NG (normal glomerular function), up to 100 podocytes, and GP (probable
      glomerulopathy), more than 100 podocytes. Urinary creatinine was measured by the
      alkaline picrate method. The variables analyzed were body mass index, gestational
      age, and systolic and diastolic blood pressure at the time of sample collection.
      Data were analyzed using the SPSS - version 16.0 (IBM - USA). Statistical
      analysis was performed by the chi2 test, and significant differences were
      considered when p<0.05. RESULTS: The median podocyte count was 20.3 (0.0-98.1)
      for group GN, and 176.9 (109.1-490.6) for GP. The mean body mass index was 30.2
      kg/m2 (SD=5.6), mean gestational age was 35.1 weeks (SD=2.5), median systolic
      blood pressure was 130.0 mmHg (100.0-160.0) and median diastolic blood pressure
      was 80.0 mmHg (60.0-110.0). There was no significant correlation between
      podocyturia and body mass index (p=0.305), gestational age (p=0.392), systolic
      blood pressure (p=0.540) or diastolic blood pressure (p=0.540). CONCLUSIONS: In
      this study, there was no podocyturia pattern consistent with the presence of
      active renal disease, although some of the women studied (15.8%) exhibited a
      significant loss. We believe that it is premature to recommend the inclusion of
      the determination of podocyturia in routine prenatal clinical practice in
      chronically hypertensive pregnant women.

PMID- 25992502
TI  - Genetic analysis and cAMP measurement: comparison between lean and obese
      anovulating mice.
AB  - PURPOSE: To evaluate genes differentially expressed in ovaries from lean (wild
      type) and obese (ob/ob) female mice and cyclic AMP production in both groups.
      METHODS: The expression on messenger RNA levels of 84 genes concerning obesity
      was analyzed through the PCR array, and cyclic AMP was quantified by the enzyme
      immunoassay method. RESULTS: The most downregulated genes in the Obesity Group
      included adenylate cyclase-activating polypeptide type 1, somatostatin,
      apolipoprotein A4, pancreatic colipase, and interleukin-1 beta. The mean decrease
      in expression levels of these genes was around 96, 40, 9, 4.2 and 3.6-fold,
      respectively. On the other hand, the most upregulated genes in the Obesity Group
      were receptor (calcitonin) activity-modifying protein 3, peroxisome proliferator
      activated receptor alpha, calcitonin receptor, and corticotropin-releasing
      hormone receptor 1. The increase means in the expression levels of such genes
      were 2.3, 2.7, 4.8 and 6.3-fold, respectively. The ovarian cyclic AMP production
      was significantly higher in ob/ob female mice (2,229 +/- 52 fMol) compared to the
      Control Group (1,814 +/- 45 fMol). CONCLUSIONS: Obese and anovulatory female mice
      have reduced reproductive hormone levels and altered ovogenesis. Several genes
      have their expression levels altered when leptin is absent, especially adenylate
      cyclase-activating polypeptide type 1.

PMID- 25992503
TI  - Herlyn-Werner-Wunderlich syndrome: a case report.
AB  - Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital disorder of the
      Mullerian ducts in which there is uterus didelphys, obstructed hemivagina and
      unilateral renal agenesis. The most common presentation is an abdominal mass
      secondary to hematocolpos, pain and dysmenorrhea. However, in some cases, such as
      the one we present here, menses are normal due to an obstructed hemivagina, and
      diagnosis can be delayed. We describe evaluation and surgical management of a 13
      year-old girl with this condition who was diagnosed by computed tomography (CT)
      scan and confirmed by pelvic ultrasound and surgical exploration, as well as a
      review of the literature. 

PMID- 25992504
TI  - Arteriography for Lower Gastrointestinal Hemorrhage: Role of Preceding Abdominal
      Computed Tomographic Angiogram in Diagnosis and Localization.
AB  - IMPORTANCE: Optimizing the nature and sequence of diagnostic imaging when
      managing lower gastrointestinal hemorrhage may reduce subsequent morbidity and
      mortality. OBJECTIVES: To determine if preceding visceral arteriography with
      computed tomographic angiography (CTA) in acute lower gastrointestinal hemorrhage
      increases hemorrhage identification and localization and to determine if CTA was
      superior to nuclear scintigraphy when used as a pre-angiogram test. DESIGN,
      SETTING, AND PARTICIPANTS: Analysis was conducted of prospectively acquired data
      from an interventional radiology database and of individual electronic medical
      records from an academic tertiary medical center. On January 1, 2009, a new,
      evidence-based, institutional protocol that formally incorporated CTA to manage
      acute lower gastrointestinal hemorrhage was launched after multidisciplinary
      consultation. All records of patients who underwent visceral angiography (VA) for
      acute lower gastrointestinal hemorrhage from January 1, 2005, to December 31,
      2012, were evaluated. EXPOSURES: Imaging, procedural, and operative details were
      abstracted from the medical records of all patients who underwent VA for lower
      gastrointestinal hemorrhage. MAIN OUTCOMES AND MEASURES: Visceral angiography
      results and efficacy were compared in patients before and after protocol
      implementation and compared based on which imaging method was used prior to
      angiography. RESULTS: A total of 161 angiographic procedures were performed
      during the study period (78 before and 83 after protocol implementation). Use of
      CTA increased from 3.8% to 56.6%, and use of nuclear scintigraphy decreased from
      83.3% to 50.6% following protocol implementation (P < .001). Preceding
      angiography with CTA resulted in similar angiography contrast administration
      (mean [SD] amount for CTA prior to VA, 135 [63] vs 160 [77] mL; P = .18) and
      fluoroscopy time (mean [SD], 26.3 [16.8] vs 32.2 [34.9] minutes; P = .34).
      Although nuclear scintigraphy and CTA had similar sensitivity and specificity,
      localization of hemorrhage site by CTA was more precise and consistent with
      angiography findings. As a pre-angiography test, compared with nuclear
      scintigraphy, CTA reduced overall the number of imaging studies required (mean
      [SD] number per patient admission, 2.1 [0.3] vs 2.5 [0.8]; P = .005) and resulted
      in administration of more overall contrast (mean [SD], 220 [80] vs 130 [70] mL; P
      < .001) without worsening renal function. CONCLUSIONS AND RELEVANCE: Preceding VA
      with a diagnostic study improves positive localization of the site of lower
      gastrointestinal hemorrhage compared with VA alone. Increasing the use of CTA for
      pre-angiography imaging may reduce overall imaging studies while appearing to
      increase positive yield at VA. Computed tomographic angiography can be used as
      part of a lower intestinal hemorrhage management algorithm and does not appear to
      worsen renal function despite the additional contrast load.

PMID- 25992507
TI  - A secure communication using cascade chaotic computing systems on clinical
      decision support.
AB  - Clinical decision support systems (C-DSS) provide supportive tools to the expert
      for the determination of the disease. Today, many of the support systems, which
      have been developed for a better and more accurate diagnosis, have reached a
      dynamic structure due to artificial intelligence techniques. However, in cases
      when important diagnosis studies should be performed in secret, a secure
      communication system is required. In this study, secure communication of a DSS is
      examined through a developed double layer chaotic communication system. The
      developed communication system consists of four main parts: random number
      generator, cascade chaotic calculation layer, PCM, and logical mixer layers.
      Thanks to this system, important patient data created by DSS will be conveyed to
      the center through a secure communication line. 

PMID- 25992505
TI  - Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults.
AB  - BACKGROUND: The appropriate caloric goal for critically ill adults is unclear. We
      evaluated the effect of restriction of nonprotein calories (permissive
      underfeeding), as compared with standard enteral feeding, on 90-day mortality
      among critically ill adults, with maintenance of the full recommended amount of
      protein in both groups. METHODS: At seven centers, we randomly assigned 894
      critically ill adults with a medical, surgical, or trauma admission category to
      permissive underfeeding (40 to 60% of calculated caloric requirements) or
      standard enteral feeding (70 to 100%) for up to 14 days while maintaining a
      similar protein intake in the two groups. The primary outcome was 90-day
      mortality. RESULTS: Baseline characteristics were similar in the two groups;
      96.8% of the patients were receiving mechanical ventilation. During the
      intervention period, the permissive-underfeeding group received fewer mean (+/
      SD) calories than did the standard-feeding group (835+/-297 kcal per day vs.
      1299+/-467 kcal per day, P<0.001; 46+/-14% vs. 71+/-22% of caloric requirements,
      P<0.001). Protein intake was similar in the two groups (57+/-24 g per day and
      59+/-25 g per day, respectively; P=0.29). The 90-day mortality was similar: 121
      of 445 patients (27.2%) in the permissive-underfeeding group and 127 of 440
      patients (28.9%) in the standard-feeding group died (relative risk with
      permissive underfeeding, 0.94; 95% confidence interval [CI], 0.76 to 1.16;
      P=0.58). No serious adverse events were reported; there were no significant
      between-group differences with respect to feeding intolerance, diarrhea,
      infections acquired in the intensive care unit (ICU), or ICU or hospital length
      of stay. CONCLUSIONS: Enteral feeding to deliver a moderate amount of nonprotein
      calories to critically ill adults was not associated with lower mortality than
      that associated with planned delivery of a full amount of nonprotein calories.
      (Funded by the King Abdullah International Medical Research Center; PermiT
      Current Controlled Trials number, ISRCTN68144998.).

PMID- 25992508
TI  - A multichannel bioimpedance monitor for full-body blood flow monitoring.
AB  - The design, properties, and possible diagnostic contribution of a multichannel
      bioimpedance monitor (MBM) with three independent current sources are presented
      in this paper. The simultaneous measurement of bioimpedance at 18 locations (the
      main part of the body, legs, arms, and neck) provides completely new information,
      on the basis of which more precise haemodynamic parameters can be obtained. The
      application of the MBM during various haemodynamic stages, such as resting in a
      supine position, tilting, exercise stress, and various respiration manoeuvres, is
      demonstrated. Statistical analysis on a group of 34 healthy volunteers is
      presented for demonstration of blood flow monitoring by using the proposed
      method. 

PMID- 25992509
TI  - Measurement of susceptibility artifacts with histogram-based reference value on
      magnetic resonance images according to standard ASTM F2119.
AB  - OBJECTIVE: The standard ASTM F2119 describes a test method for measuring the size
      of a susceptibility artifact based on the example of a passive implant. A pixel
      in an image is considered to be a part of an image artifact if the intensity is
      changed by at least 30% in the presence of a test object, compared to a reference
      image in which the test object is absent (reference value). The aim of this paper
      is to simplify and accelerate the test method using a histogram-based reference
      value. MATERIALS AND METHODS: Four test objects were scanned parallel and
      perpendicular to the main magnetic field, and the largest susceptibility
      artifacts were measured using two methods of reference value determination
      (reference image-based and histogram-based reference value). The results between
      both methods were compared using the Mann-Whitney U-test. RESULTS: The difference
      between both reference values was 42.35 +/- 23.66. The difference of artifact
      size was 0.64 +/- 0.69 mm. The artifact sizes of both methods did not show
      significant differences; the p-value of the Mann-Whitney U-test was between 0.710
      and 0.521. CONCLUSIONS: A standard-conform method for a rapid, objective, and
      reproducible evaluation of susceptibility artifacts could be implemented. The
      result of the histogram-based method does not significantly differ from the ASTM
      conform method.

PMID- 25992510
TI  - A review of beat-to-beat vectorcardiographic (VCG) parameters for analyzing
      repolarization variability in ECG signals.
AB  - Elevated ventricular repolarization lability is believed to be linked to the risk
      of ventricular tachycardia/ventricular fibrillation. However, ventricular
      repolarization is a complex electrical phenomenon, and abnormalities in
      ventricular repolarization are not completely understood. To evaluate
      repolarization lability, vectorcardiography (VCG) is an alternative approach
      where the electrocardiographic (ECG) signal can be considered as possessing both
      magnitude and direction. Recent research has shown that VCG is advantageous over
      ECG signal analysis for identification of repolarization abnormality. One of the
      key reasons is that the VCG approach does not rely on exact identification of the
      T-wave offset, which improves the reproducibility of the VCG technique. However,
      beat-to-beat variability in VCG is an emerging area for the investigation of
      repolarization abnormality though not yet fully realized. Therefore, the purpose
      of this review is to explore the techniques, findings, and efficacy of beat-to
      beat VCG parameters for analyzing repolarization lability, which may have
      potential utility for further study. 

PMID- 25992511
TI  - The 2008/2009 cholera outbreak in Harare, Zimbabwe: case of failure in urban
      environmental health and planning.
AB  - This paper reviews and reflects on the cholera outbreak that rocked Harare,
      Zimbabwe, in 2008/2009. We give special attention to the root causes, impacts and
      debates made by key stakeholders, indicating the political and geographical
      responses. Based on a desktop study and documentary review, the paper highlights
      the inadequacy of safe and clean water in most of the suburbs, the collapse of
      the waste management, water supply and sanitation systems of the city as the
      major explanations for the scourge. Despite this, Harare remains troubled with
      the shortage of purification chemicals, making it quite impossible to supply
      clean and adequate water. The national economic crisis also had a strong bearing
      against the performance of the public health sector. The paper concludes that
      sustainable urban health initiatives involving both central and local government
      will provide a long-term solution to the problems highlighted. 

PMID- 25992512
TI  - Temporal phases of long-term potentiation (LTP): myth or fact?
AB  - Long-term potentiation (LTP) remains the most widely accepted model for learning
      and memory. In accordance with this belief, the temporal differentiation of LTP
      into early and late phases is accepted as reflecting the differentiation of short
      term and long-term memory. Moreover, during the past 30 years, protein synthesis
      inhibitors have been used to separate the early, protein synthesis-independent (E
      LTP) phase and the late, protein synthesis-dependent (L-LTP) phase. However, the
      role of these proteins has not been formally identified. Additionally, several
      reports failed to show an effect of protein synthesis inhibitors on LTP. In this
      review, a detailed analysis of extensive behavioral and electrophysiological data
      reveals that the presumed correspondence of LTP temporal phases to memory phases
      is neither experimentally nor theoretically consistent. Moreover, an overview of
      the time courses of E-LTP in hippocampal slices reveals a wide variability
      ranging from <1 h to more than 5 h. The existence of all these conflictual
      findings should lead to a new vision of LTP. We believe that the E-LTP vs. L-LTP
      distinction, established with protein synthesis inhibitor studies, reflects a
      false dichotomy. We suggest that the duration of LTP and its dependency on
      protein synthesis are related to the availability of a set of proteins at
      synapses and not to the de novo synthesis of plasticity-related proteins. This
      availability is determined by protein turnover kinetics, which is regulated by
      previous and ongoing electrical activities and by energy store availability. 

PMID- 25992513
TI  - Towards biomarker-based tests that can facilitate decisions about prevention and
      management of preeclampsia in low-resource settings.
AB  - In recent years, an increasing amount of literature is emerging on candidate
      urine and blood-based biomarkers associated with incidence and severity of
      preeclampsia (PE) in pregnant women. While enthusiasm on the usefulness of
      several of these markers in predicting PE is evolving, essentially all work so
      far has focused on the needs of high-resource settings and high-income countries,
      resulting primarily in multi-parameter laboratory assays based on proteomic and
      metabolomics analysis techniques. These highly complex methods, however, require
      laboratory capabilities that are rarely available or affordable in low-resource
      settings (LRS). The importance of quantifying maternal and perinatal risks and
      identifying which pregnancies can be safely prolonged is also much greater in
      LRS, where intensive care facilities that can rapidly respond to PE-related
      health threats for women and infants are limited. For these reasons, simple, low
      cost, sensitive, and specific point-of-care (POC) tests are needed that can be
      performed by antenatal health care providers in LRS and that can facilitate
      decisions about detection and management of PE. Our study aims to provide a
      comprehensive systematic review of current and emerging blood and urine
      biomarkers for PE, not only on the basis of their clinical performance, but also
      of their suitability to be used in LRS-compatible test formats, such as lateral
      flow and other variants of POC rapid assays. 

PMID- 25992514
TI  - Once upon a time: a tale of ISO 15189 accreditation.

PMID- 25992515
TI  - Genetic of dystonias according the new classification.

PMID- 25992516
TI  - The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01
      allele as a putative susceptibility factor to multiple sclerosis in Brazilian
      females.
AB  - The objective of this study was to investigate the association between the HLA
      alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G
      and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio
      de Janeiro State, Brazil. Furthermore, we wished to determine whether any of
      these associations might be more significant in women compared with men. DNA
      samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls
      matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01
      MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001).
      Furthermore, we observed that the +1614G/C mutation in combination with the HLA
      DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p =
      0.01). Together, these findings highlight the polygenic nature of MS. 

PMID- 25992517
TI  - Lack of association between the prothrombin rs1799963 polymorphism and juvenile
      myoclonic epilepsy.
AB  - Juvenile myoclonic epilepsy (JME) accounts for 26% of generalized idiopathic
      epileptic syndromes. The highest levels of thrombin activity are closely involved
      in the development of neurological diseases, including epilepsy. The prothrombin
      c.20210G>A (rs1799963) variation, which alters prothrombin mRNA stability, is
      associated with high plasma prothrombin levels. OBJECTIVE: The present study was
      designed to investigate whether the SNP rs1799963 is a risk factor for JME in the
      northeastern Brazilian population. RESULTS: The polymorphism was genotyped in 207
      controls and 123 patients using polymerase chain reaction-restriction fragment
      length polymorphism method. No significant differences were observed in the
      genotype and allele frequencies of this polymorphism between cases and controls.
      CONCLUSION: These results present no evidence for an association of rs1799963
      with JME. Further studies including other types of epilepsy are required to
      investigate the involvement of prothrombin gene in the genetic susceptibility to
      chronic seizure.

PMID- 25992518
TI  - Evaluation of the efficacy of sodium valproate in convulsive status epilepticus
      following to ischemic stroke.
AB  - OBJECTIVE: Convulsive status epilepticus (CSE) is very rarely observed after
      ischaemic stroke. Sodium valproate (SV) is one of the agents used in the
      treatment of CSE, but its role still controversial, and its degree of efficacy in
      treating CSE that develops following stroke is unclear. METHOD: We evaluated 19
      patients who were treated with intravenous (IV) SV (20 mg/kg, 2 mg/kg/h-12h)
      after diazepam. Patients' modified Rankin scores (mRS), SE types, and changes in
      biochemical parameters after treatment were assessed. RESULTS: CSE was
      successfully treated in 12 (63.15%) patients. Side effects such as hypotension
      and allergic reactions were observed in two patients. Refractory SE development
      was observed in 5 (29.4%) patients with high mRS (? 3). No significant
      deterioration in patients' laboratory evaluations, conducted before and after
      status, was observed. CONCLUSION: SV may be safe and effective in the treatment
      of CSE observed after ischaemic stroke, especially in patients with low mRS.

PMID- 25992519
TI  - The social context and the need of information from patients with epilepsy:
      evaluating a tertiary referral service.
AB  - OBJECTIVE: Characterize the social profile and the need of information from
      patients with refractory epilepsy. METHOD: A semi-structured questionnaire was
      applied to 103 patients to investigate sociodemographic aspects, pharmacotherapy
      and any doubts about epilepsy. RESULTS: Patients were highly dependent on having
      a free and accessible supply of antiepileptic drugs. Sixty-eight percent of the
      population was unemployed, and 26% confirmed receiving social security benefits
      due to epilepsy. Twenty-nine percent of the population reached high school.
      Eighty-five percent of the patients had at least one doubt about epilepsy;
      treatment and epilepsy aspects in general were the main topics. CONCLUSION: As
      observed in developed countries, patients with refractory epilepsy from a
      developing country also have high rates of unemployment and low educational
      levels. The results raise a concern about the need of information about epilepsy
      by patients and their families, urging the necessity to invest in strategies to
      solve this deficiency in knowledge.

PMID- 25992520
TI  - The profile of patients followed at the Neuroimmunology Clinic at UNIFESP: 20
      years analysis.
AB  - OBJECTIVE: To describe the clinical activities at the Neuroimmunology Clinic of
      the Universidade Federal de Sao Paulo (UNIFESP) from 1994 to 2013. METHOD: The
      final diagnosis of all patients that attended the center was reviewed and
      established upon specific guidelines for each disease. The number of total
      appointments and extra clinical activities (reports and prescriptions) were also
      analyzed, as are part of routine activities. RESULTS: 1,599 patients attended the
      Clinic from 1994 to 2013: 816 with multiple sclerosis (MS), 172 with clinical
      isolated syndromes, 178 with neuromyelitis optica (NMO), 216 with other
      demyelinating disease, 20 with metabolic disorder, 42 with a vascular disease and
      155 with other or undetermined diagnosis. A mean 219 outpatient visits and 65
      extra clinical activities were performed monthly. CONCLUSION: We identified that
      15% of patients seen have NMO. As patients with NMO have a more severe disease
      than MS, this data may be important for planning local health care policies.

PMID- 25992521
TI  - Visual evoked potentials show strong positive association with intracranial
      pressure in patients with cryptococcal meningitis.
AB  - OBJECTIVE: To verify the relationship between intracranial pressure and flash
      visual evoked potentials (F-VEP) in patients with cryptococcal meningitis. Method
      The sample included adults diagnosed with cryptococcal meningitis admitted at a
      reference hospital for infectious diseases. The patients were subjected to F-VEP
      tests shortly before lumbar puncture. The Pearson?s linear correlation
      coefficient was calculated and the linear regression analysis was performed.
      RESULTS: Eighteen individuals were subjected to a total of 69 lumbar punctures
      preceded by F-VEP tests. At the first lumbar puncture performed in each patient,
      N2 latency exhibited a strong positive correlation with intracranial pressure (r
      = 0.83; CI = 0.60 - 0.94; p < 0.0001). The direction of this relationship was
      maintained in subsequent punctures. CONCLUSION: The intracranial pressure
      measured by spinal tap manometry showed strong positive association with the N2
      latency F-VEP in patients with cryptococcal meningitis.

PMID- 25992522
TI  - Sound localization and word discrimination in reverberant environment in children
      with developmental dyslexia.
AB  - OBJECTIVE: Compare if localization of sounds and words discrimination in
      reverberant environment is different between children with dyslexia and controls.
      METHOD: We studied 30 children with dyslexia and 30 controls. Sound and word
      localization and discrimination was studied in five angles from left to right
      auditory fields (-90o, -45o, 0o, +45o, +90o), under reverberant and no
      reverberant conditions; correct answers were compared. RESULTS: Spatial location
      of words in no-reverberant test was deficient in children with dyslexia at 0o and
      +90o. Spatial location for reverberant test was altered in children with dyslexia
      at all angles, except ?-90o. Word discrimination in no-reverberant test in
      children with dyslexia had a poor performance at left angles. In reverberant
      test, children with dyslexia exhibited deficiencies at -45o, -90o, and +45o
      angles. CONCLUSION: Children with dyslexia could had problems when have to locate
      sound, and discriminate words in extreme locations of the horizontal plane in
      classrooms with reverberation.

PMID- 25992523
TI  - The effects of bromazepam over the central and frontal areas during a motor task:
      an EEG study.
AB  - The present study investigates the influence of bromazepam while executing a
      motor task. Specifically, we intend to analyze the changes in alpha absolute
      power under two experimental conditions, bromazepam and placebo. We also included
      analyses of theta and beta frequencies. We collected electroencephalographic data
      before, during, and after motor task execution. We used a Two Way ANOVA to
      investigate the condition (PL * Br6 mg) and moment (pre and post) variables for
      the following electrodes: Fp1, Fp2, F7, F3, Fz, F4, F8, C3, CZ and C4. We found a
      main effect for condition on the electrodes FP1, F7, F3, Fz, F4, C3 and CZ, for
      alpha and beta bands. For beta band we also found a main effect for condition on
      the electrodes Fp2, F8 and C4; for theta band we identified a main effect for
      condition on C3, Cz and C4 electrodes. This finding suggests that the motor task
      did not have any influence on the electrocortical activity in alpha, and that the
      existing modifications were a consequence due merely to the drug use. Despite its
      anxiolytic and sedative action, bromazepam did not show any significant changes
      when the individuals executed a finger extension motor task. 

PMID- 25992524
TI  - Survival analysis in patients with metastatic spinal disease: the influence of
      surgery, histology, clinical and neurologic status.
AB  - Spine is the most common site for skeletal metastasis in patients with
      malignancy. Vertebral involvement quantification, neurological status, general
      health status and primary tumor histology are factors to set surgical planning
      and therapeutic targets. We evaluated the impact of general clinical and
      neurological status, histologic type and surgery in survival. METHOD: The study
      sample consisted of consecutive patients admitted from July 2010 to January 2013
      for treatment. RESULTS: Sixty eight patients were evaluated. 23 were female and
      45 were male. Main primary neoplasic sites were: breast, prostate, lung/pleura
      and linfoproliferative. Thirty three out of 68 received surgical treatment, 2
      received percutaneous biopsy and 33 had nonsurgical treatment. SURVIVAL: Log Rank
      curves revealed no statistical significant difference according to histological
      type, surgical approach and Frankel Score. Karnofsky Score was statistically
      different. CONCLUSION: Histological type and clinical status were statistically
      associated with life expectancy in vertebral metastatic disease.

PMID- 25992525
TI  - Upper airway dimensions in patients with craniocervical junction malformations
      with and without sleep apnea. A pilot case-control study.
AB  - OBJECTIVE: Patients with craniocervical junction malformations (CCJM) tend to
      suffer more frequently from sleep respiratory disturbances, which are more
      frequent and severe in patients with basilar invagination. Here we evaluate if
      patients with CCJM and sleep respiratory disorders (SRD) present smaller airway
      dimensions than patients without SRD. METHOD: Patients with CCCM with and without
      sleep respiratory disturbances were evaluated clinically by Bindal's score,
      modified Mallampati classification, full-night polysomnography and upper airway
      cone beam tomography. RESULTS: Eleven patients had sleep respiratory disorders
      (SRD), and nine patients performed control group without SRD. CCJM patients with
      SRD were predominantly female, older, had higher BMI, were more likely to have
      Mallampati grades 3 and 4 and had statistically significant smaller
      anteroposterior diameter of the upper airway than patients without SRD.
      CONCLUSION: Patients with CCJM and sleep respiratory disturbances have higher
      BMI, higher Mallampati score and smaller anterior posterior diameter of the upper
      airway.

PMID- 25992526
TI  - Proteomics analysis after traumatic brain injury in rats: the search for
      potential biomarkers.
AB  - Many studies of protein expression after traumatic brain injury (TBI) have
      identified biomarkers for diagnosing or determining the prognosis of TBI. In this
      study, we searched for additional protein markers of TBI using a fluid perfusion
      impact device to model TBI in S-D rats. Two-dimensional gel electrophoresis and
      mass spectrometry were used to identify differentially expressed proteins. After
      proteomic analysis, we detected 405 and 371 protein spots within a pH range of 3
      10 from sham-treated and contused brain cortex, respectively. Eighty protein
      spots were differentially expressed in the two groups and 20 of these proteins
      were identified. This study validated the established biomarkers of TBI and
      identified potential biomarkers that could be examined in future work. 

PMID- 25992527
TI  - The genetics of the dystonias--a review based on the new classification of the
      dystonias.
AB  - The definition and classification of the dystonias was recently revisited. In the
      new 2013 classification, the dystonias are subdivided in terms of their etiology
      according to whether they are the result of pathological changes or structural
      damage, have acquired causes or are inherited. As hereditary dystonias are
      clinically and genetically heterogeneous, we sought to classify them according to
      the new recently defined criteria. We observed that although the new
      classification is still the subject of much debate and controversy, it is easy to
      use in a logical and objective manner with the inherited dystonias. With the
      discovery of new genes, however, it remains to be seen whether the new
      classification will continue to be effective. 

PMID- 25992528
TI  - Shakespeare's: his 450 th birth anniversary and his insights into neurology and
      cognition.
AB  - The works of William Shakespeare (1564-1616), the greatest dramatist and poet of
      the English language, reflect several cultural values of the Western world which
      are also shared by other cultures. On his 450 th birthday, many of his concepts
      are admired as descriptions of human feelings and neurological phenomena,
      demonstrating his insights into what it is today considered cognitive
      neuroscience.

PMID- 25992529
TI  - Low signal intensity of motor cortex in SWI sequence: a radiological marker for
      motor neuron disease?

PMID- 25992530
TI  - PET-CT imaging in a patient with progressive supranuclear palsy.

PMID- 25992531
TI  - Hypomelanosis of Ito presenting with adult-onset dementia and marked enlarged
      Virchow-Robin spaces.

PMID- 25992532
TI  - Dengue and brain hemorrhage.

PMID- 25992533
TI  - Neurological manifestation on Leishmania siamensis: existed or not?

PMID- 25992534
TI  - A specific vaccine to protect patients with multiple sclerosis from herpes
      zoster.

PMID- 25992535
TI  - [Cannabinoids in neurology--Brazilian Academy of Neurology].
AB  - The use of cannabidiol in some neurological conditions was allowed by Conselho
      Regional de Medicina de Sao Paulo and by Agencia Nacional de Vigilancia Sanitaria
      (ANVISA). Specialists on behalf of Academia Brasileira de Neurologia prepared a
      critical statement about use of cannabidiol and other cannabis derivatives in
      neurological diseases. 

PMID- 25992536
TI  - Urinary protein/creatinine ratio weighted by estimated urinary creatinine
      improves the accuracy of predicting daily proteinuria.
AB  - BACKGROUND: The spot urine protein/creatinine ratio (UPCR) is proposed to be a
      substitute for 24-hour urinary protein (24h-UP). This study is aimed to determine
      whether the predictive accuracy of 24h-UP using UPCR can be improved by simply
      multiplying estimated daily urine creatinine excretion (eUCr) and UPCR together.
      METHODS: This study enrolled 120 participants to investigate the correlation
      between spot UPCR and 24h-UP. Three sets of spot urine samples were randomly
      collected throughout the day and night, along with the first morning void. UPCR
      was weighted by eUCr to investigate the improvement of accuracy in using spot
      urine samples to predict 24h-UP. RESULTS: There were strong correlation and
      concordance between UPCR and 24h-UP irrespective of the time of spot urine
      sampling, and the correlation, concordance and agreement were improved after
      multiplying the UPCR value by the eUCr. Greater improvement was found in the
      subgroups with measured daily urine creatinine excretion <= 0.8 g/d and >= 1.2
      g/d. CONCLUSIONS: This investigation demonstrated that multiplying UPCR by eUCr
      can improve the accuracy of only using UPCR to predict 24h-UP.

PMID- 25992537
TI  - Procalcitonin is a marker of gram-negative bacteremia in patients with sepsis.
AB  - BACKGROUND: Prediction of the species of pathogen among patients with sepsis
      within hours would be helpful in accelerating proper treatment. As a potential
      method of shortening the time to identification, this study considered the
      usefulness of measuring procalcitonin (PCT) to predict blood culture (BC)
      results. METHODS: The authors retrospectively analyzed the data of patients with
      a diagnosis of sepsis in their hospital from December 2012 to December 2013. The
      authors analyzed all diagnostic episodes consisting of BC and PCT concentration.
      The diagnostic performance of PCT to predict gram-negative bacteremia was tested
      using a receiver operative characteristic curve. Logistic regression was
      constructed using the presence of gram-negative bacteria as the dependent
      variable. RESULTS: A total of 262 diagnostic episodes met the inclusion criteria.
      According to BC classifications, a significantly higher value of PCT was observed
      in bloodstream infections caused by gram-negative bacteria (26.7 ng/mL, 0.09
      188.3) than that in bloodstream infections caused by gram-positive bacteria (0.84
      ng/mL, 0.05-18.79) or Candida spp. (1.12 ng/mL, 0.07-49.68). A cutoff value of >=
      3.39 ng/mL for PCT showed a sensitivity of 80%, a specificity of 71%, a positive
      predictive value of 35%, a negative predictive value of 91% and an area under the
      curve of 0.73 for gram-negative bacteremia identification by BC. Among the 122
      diagnostic episodes with positive BC results, a cutoff value of >= 6.47 ng/mL for
      PCT yielded a sensitivity of 74%, a specificity of 81%, a positive predictive
      value of 82%, a negative predictive value of 75% and an area under the curve of
      0.81 for gram-negative bacteremia identification. CONCLUSIONS: PCT may represent
      a useful tool for differentiating gram-positive from gram-negative bloodstream
      infection with a significantly higher PCT level indicating gram-negative
      bacteremia.

PMID- 25992540
TI  - Pragmatism Instead of Mechanism: A Call for Impactful Biological Psychiatry.

PMID- 25992541
TI  - Multimodal imaging for detection of clinically inapparent diffuse iris juvenile
      xanthogranuloma.
AB  - A 6-month-old female infant was referred following three episodes of spontaneous
      hyphema. Iris juvenile xanthogranuloma was suspected but not clinically visible.
      Multimodal imaging with fluorescein angiography, anterior segment optical
      coherence tomography, and ultrasound biomicroscopy were used to detect the flat,
      transparent lesion and cytopathology confirmed juvenile xanthogranuloma.

PMID- 25992542
TI  - Microbiology: Taking the bad with the good.

PMID- 25992543
TI  - Developmental biology: Diversity in the   lymphatic vasculature.

PMID- 25992544
TI  - Cardiac lymphatics are heterogeneous in origin and respond to injury.
AB  - The lymphatic vasculature is a blind-ended network crucial for tissue-fluid
      homeostasis, immune surveillance and lipid absorption from the gut. Recent
      evidence has proposed an entirely venous-derived mammalian lymphatic system. By
      contrast, here we show that cardiac lymphatic vessels in mice have a
      heterogeneous cellular origin, whereby formation of at least part of the cardiac
      lymphatic network is independent of sprouting from veins. Multiple Cre-lox-based
      lineage tracing revealed a potential contribution from the putative haemogenic
      endothelium during development, and discrete lymphatic endothelial progenitor
      populations were confirmed by conditional knockout of Prox1 in Tie2+ and Vav1+
      compartments. In the adult heart, myocardial infarction promoted a significant
      lymphangiogenic response, which was augmented by treatment with VEGF-C, resulting
      in improved cardiac function. These data prompt the re-evaluation of a century
      long debate on the origin of lymphatic vessels and suggest that lymphangiogenesis
      may represent a therapeutic target to promote cardiac repair following injury.

PMID- 25992545
TI  - Lymphatic vessels arise from specialized angioblasts within a venous niche.
AB  - How cells acquire their fate is a fundamental question in developmental and
      regenerative biology. Multipotent progenitors undergo cell-fate restriction in
      response to cues from the microenvironment, the nature of which is poorly
      understood. In the case of the lymphatic system, venous cells from the cardinal
      vein are thought to generate lymphatic vessels through trans-differentiation.
      Here we show that in zebrafish, lymphatic progenitors arise from a previously
      uncharacterized niche of specialized angioblasts within the cardinal vein, which
      also generates arterial and venous fates. We further identify Wnt5b as a novel
      lymphatic inductive signal and show that it also promotes the 'angioblast-to
      lymphatic' transition in human embryonic stem cells, suggesting that this process
      is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic
      specification, and provide the first characterization of the lymphatic inductive
      niche. More broadly, our findings highlight the cardinal vein as a heterogeneous
      structure, analogous to the haematopoietic niche in the aortic floor.

PMID- 25992546
TI  - Counteraction of antibiotic production and degradation stabilizes microbial
      communities.
AB  - A major challenge in theoretical ecology is understanding how natural microbial
      communities support species diversity, and in particular how antibiotic
      producing, -sensitive and -resistant species coexist. While cyclic 'rock-paper
      scissors' interactions can stabilize communities in spatial environments,
      coexistence in unstructured environments remains unexplained. Here, using
      simulations and analytical models, we show that the opposing actions of
      antibiotic production and degradation enable coexistence even in well-mixed
      environments. Coexistence depends on three-way interactions in which an
      antibiotic-degrading species attenuates the inhibitory interactions between two
      other species. These interactions enable coexistence that is robust to
      substantial differences in inherent species growth rates and to invasion by
      'cheating' species that cease to produce or degrade antibiotics. At least two
      antibiotics are required for stability, with greater numbers of antibiotics
      enabling more complex communities and diverse dynamic behaviours ranging from
      stable fixed points to limit cycles and chaos. Together, these results show how
      multi-species antibiotic interactions can generate ecological stability in both
      spatially structured and mixed microbial communities, suggesting strategies for
      engineering synthetic ecosystems and highlighting the importance of toxin
      production and degradation for microbial biodiversity.

PMID- 25992547
TI  - A Genetic Screen for Pathogenicity Genes in the Hemibiotrophic Fungus
      Colletotrichum higginsianum Identifies the Plasma Membrane Proton Pump Pma2
      Required for Host Penetration.
AB  - We used insertional mutagenesis by Agrobacterium tumefaciens mediated
      transformation (ATMT) to isolate pathogenicity mutants of Colletotrichum
      higginsianum. From a collection of 7200 insertion mutants we isolated 75 mutants
      with reduced symptoms. 19 of these were affected in host penetration, while 17
      were affected in later stages of infection, like switching to necrotrophic
      growth. For 16 mutants the location of T-DNA insertions could be identified by
      PCR. A potential plasma membrane H(+)-ATPase Pma2 was targeted in five
      independent insertion mutants. We genetically inactivated the Ku80 component of
      the non-homologous end-joining pathway in C. higginsianum to establish an
      efficient gene knockout protocol. Chpma2 deletion mutants generated by homologous
      recombination in the DeltaChku80 background form fully melanized appressoria but
      entirely fail to penetrate the host tissue and are non-pathogenic. The ChPMA2
      gene is induced upon appressoria formation and infection of A. thaliana. Pma2
      activity is not important for vegetative growth of saprophytically growing
      mycelium, since the mutant shows no growth penalty under these conditions.
      Colletotrichum higginsianum codes for a closely related gene (ChPMA1), which is
      highly expressed under most growth conditions. ChPMA1 is more similar to the
      homologous yeast genes for plasma membrane pumps. We propose that expression of a
      specific proton pump early during infection may be common to many appressoria
      forming fungal pathogens as we found ChPMA2 orthologs in several plant pathogenic
      fungi.

PMID- 25992550
TI  - Bat-fruit interactions are more specialized in shaded-coffee plantations than in
      tropical mountain cloud forest fragments.
AB  - Forest disturbance causes specialization of plant-frugivore networks and
      jeopardizes mutualistic interactions through reduction of ecological redundancy.
      To evaluate how simplification of a forest into an agroecosystem affects plant
      disperser mutualistic interactions, we compared bat-fruit interaction indexes of
      specialization in tropical montane cloud forest fragments (TMCF) and shaded
      coffee plantations (SCP). Bat-fruit interactions were surveyed by collection of
      bat fecal samples. Bat-fruit interactions were more specialized in SCP (mean H2 '
      = 0.55) compared to TMCF fragments (mean H2 ' = 0.27), and were negatively
      correlated to bat abundance in SCP (R = -0.35). The number of shared plant
      species was higher in the TMCF fragments (mean = 1) compared to the SCP (mean =
      0.51) and this was positively correlated to the abundance of frugivorous bats (R=
      0.79). The higher specialization in SCP could be explained by lower bat abundance
      and lower diet overlap among bats. Coffee farmers and conservation policy makers
      must increase the proportion of land assigned to TMCF within agroecosystem
      landscapes in order to conserve frugivorous bats and their invaluable seed
      dispersal service. 

PMID- 25992549
TI  - Nutrient distribution indicated whole-tree harvesting as a possible factor
      restricting the sustainable productivity of a poplar plantation system in China.
AB  - We evaluated the biomass and contents of five major macronutrients (N, P, K, Ca
      and Mg) in 10-year-old poplar trees (Populus deltoids Bartr. cv. "Lux"), and
      determined their nutrient use efficiencies (NUEs) at Zhoushan Forestry Farm (32
      degrees 20' N, 119 degrees 40' E), Jiangsu province, in eastern China. The above-
      and below-ground biomass of poplar trees was 161.7 t ha(-1), of which 53.3% was
      stemwood. The nutrient contents in the aboveground part were as follows: 415.1 kg
      N ha(-1), 29.7 kg P ha(-1), 352.0 kg K ha(-1), 1083.0 kg Ca ha(-1), and 89.8 kg
      Mg ha(-1). The highest nutrient contents were in stembark, followed by branches,
      roots, stemwood, and foliage. The NUEs of the aboveground parts of poplar for N,
      P, K, Ca and Mg were 0.313, 4.377, 0.369, 0.120, 1.448 t dry biomass kg(-1)
      nutrient, respectively, while those of stemwood were 1.294, 33.154, 1.253, 0.667,
      and 3.328 t dry biomass kg(-1), respectively. The cycling coefficients, defined
      as the percentage of annual nutrient return in annual nutrient uptake, of N, P,
      K, Ca and Mg for the aboveground part were 87, 95, 69, 92, and 84%, respectively.
      Based on the NUE and nutrient cycling characteristics, shifting from whole-tree
      harvesting to stemwood-only harvesting and appropriately extending the harvest
      rotation could prevent site deterioration and support sustainable productivity of
      poplar plantation systems.

PMID- 25992548
TI  - Application of RNAi to Genomic Drug Target Validation in Schistosomes.
AB  - Concerns over the possibility of resistance developing to praziquantel (PZQ), has
      stimulated efforts to develop new drugs for schistosomiasis. In addition to the
      development of improved whole organism screens, the success of RNA interference
      (RNAi) in schistosomes offers great promise for the identification of potential
      drug targets to initiate drug discovery. In this study we set out to contribute
      to RNAi based validation of putative drug targets. Initially a list of 24 target
      candidates was compiled based on the identification of putative essential genes
      in schistosomes orthologous of C. elegans essential genes. Knockdown of
      Calmodulin (Smp_026560.2) (Sm-Calm), that topped this list, produced a phenotype
      characterised by waves of contraction in adult worms but no phenotype in
      schistosomula. Knockdown of the atypical Protein Kinase C (Smp_096310) (Sm-aPKC)
      resulted in loss of viability in both schistosomula and adults and led us to
      focus our attention on other kinase genes that were identified in the above list
      and through whole organism screening of known kinase inhibitor sets followed by
      chemogenomic evaluation. RNAi knockdown of these kinase genes failed to affect
      adult worm viability but, like Sm-aPKC, knockdown of Polo-like kinase 1, Sm-PLK1
      (Smp_009600) and p38-MAPK, Sm-MAPK p38 (Smp_133020) resulted in an increased
      mortality of schistosomula after 2-3 weeks, an effect more marked in the presence
      of human red blood cells (hRBC). For Sm-PLK-1 the same effects were seen with the
      specific inhibitor, BI2536, which also affected viable egg production in adult
      worms. For Sm-PLK-1 and Sm-aPKC the in vitro effects were reflected in lower
      recoveries in vivo. We conclude that the use of RNAi combined with culture with
      hRBC is a reliable method for evaluating genes important for larval development.
      However, in view of the slow manifestation of the effects of Sm-aPKC knockdown in
      adults and the lack of effects of Sm-PLK-1 and Sm-MAPK p38 on adult viability,
      these kinases may not represent suitable drug targets. 

PMID- 25992551
TI  - Tumor grafting induces changes of gut microbiota in athymic nude mice in the
      presence and absence of medicinal Gynostemma saponins.
AB  - Recent findings have revealed that gut microbiota plays a substantial role in
      modulating diseases such as autism, rheumatoid arthritis, allergies, and cancer
      that occur at sites distant to the gut. Athymic nude mice have been employed for
      tumorigenic research for decades; however, the relationships between the gut
      microbiome and host's response in drug treatment to the grafted tumors have not
      been explored. In this study, we analyzed the fecal microbiome of nonxenograft
      and xenograft nude mice treated with phytosaponins from a popular medicinal
      plant, Gynostemma pentaphyllum (Gp). Analysis of enterobacterial repetitive
      intergenic consensus (ERIC)-PCR data showed that the microbiota profile of
      xenograft mice departed from that of the nonxenograft mice. After ten days of
      treatment with Gp saponins (GpS), the microbiota of the treated mice was closer
      to the microbiota at Day 0 before the implantation of the tumor. Data obtained
      from 16S pyrosequencing of fecal samples reiterates the differences in microbiome
      between the nonxenograft and xenograft mice. GpS markedly increased the relative
      abundance of Clostridium cocleatum and Bacteroides acidifaciens, for which the
      beneficial effects on the host have been well documented. This study, for the
      first time, characterizes the properties of gut microbiome in nude mice
      responding to tumor implant and drug treatment. We also demonstrate that dietary
      saponins such as GpS can potentially regulate the gut microbial ecosystem by
      increasing the number of symbionts. Interestingly, this regulation of the gut
      ecosystem might, at least in part, be responsible for or contribute to the
      anticancer effect of GpS. 

PMID- 25992552
TI  - Surveillance for Neisseria meningitidis Disease Activity and Transmission Using
      Information Technology.
AB  - BACKGROUND: While formal reporting, surveillance, and response structures remain
      essential to protecting public health, a new generation of freely accessible,
      online, and real-time informatics tools for disease tracking are expanding the
      ability to raise earlier public awareness of emerging disease threats. The
      rationale for this study is to test the hypothesis that the HealthMap informatics
      tools can complement epidemiological data captured by traditional surveillance
      monitoring systems for meningitis due to Neisseria meningitides (N. meningitides)
      by highlighting severe transmissible disease activity and outbreaks in the United
      States. METHODS: Annual analyses of N. meningitides disease alerts captured by
      HealthMap were compared to epidemiological data captured by the Centers for
      Disease Control's Active Bacterial Core surveillance (ABCs) for N. meningitides.
      Morbidity and mortality case reports were measured annually from 2010 to 2013
      (HealthMap) and 2005 to 2012 (ABCs). FINDINGS: HealthMap N. meningitides
      monitoring captured 80-90% of alerts as diagnosed N. meningitides, 5-20% of
      alerts as suspected cases, and 5-10% of alerts as related news articles.
      HealthMap disease alert activity for emerging disease threats related to N.
      meningitides were in agreement with patterns identified historically using
      traditional surveillance systems. HealthMap's strength lies in its ability to
      provide a cumulative "snapshot" of weak signals that allows for rapid
      dissemination of knowledge and earlier public awareness of potential outbreak
      status while formal testing and confirmation for specific serotypes is ongoing by
      public health authorities. CONCLUSIONS: The underreporting of disease cases in
      internet-based data streaming makes inadequate any comparison to epidemiological
      trends illustrated by the more comprehensive ABCs network published by the
      Centers for Disease Control. However, the expected delays in compiling
      confirmatory reports by traditional surveillance systems (at the time of writing,
      ABCs data for 2013 is listed as being provisional) emphasize the helpfulness of
      real-time internet-based data streaming to quickly fill gaps including the
      visualization of modes of disease transmission in outbreaks for better resource
      and action planning. HealthMap can also contribute as an internet-based
      monitoring system to provide real-time channel for patients to report
      intervention-related failures.

PMID- 25992553
TI  - Minor Type IV Collagen alpha5 Chain Promotes Cancer Progression through Discoidin
      Domain Receptor-1.
AB  - Type IV collagens (Col IV), components of basement membrane, are essential in the
      maintenance of tissue integrity and proper function. Alteration of Col IV is
      related to developmental defects and diseases, including cancer. Col IV alpha
      chains form alpha1alpha1alpha2, alpha3alpha4alpha5 and alpha5alpha5alpha6
      protomers that further form collagen networks. Despite knowledge on the functions
      of major Col IV (alpha1alpha1alpha2), little is known whether minor Col IV
      (alpha3alpha4alpha5 and alpha5alpha5alpha6) plays a role in cancer. It also
      remains to be elucidated whether major and minor Col IV are functionally
      redundant. We show that minor Col IV alpha5 chain is indispensable in cancer
      development by using alpha5(IV)-deficient mouse model. Ablation of alpha5(IV)
      significantly impeded the development of KrasG12D-driven lung cancer without
      affecting major Col IV expression. Epithelial alpha5(IV) supports cancer cell
      proliferation, while endothelial alpha5(IV) is essential for efficient tumor
      angiogenesis. alpha5(IV), but not alpha1(IV), ablation impaired expression of non
      integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK
      activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung
      cancer cells and endothelial cells phenocopied the cells deficient of alpha5(IV).
      Constitutively active DDR1 or MEK1 rescued the defects of alpha5(IV)-ablated
      cells. Thus, minor Col IV alpha5(IV) chain supports lung cancer progression via
      DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV
      can not be functionally compensated by abundant major Col IV. 

PMID- 25992554
TI  - Changes in gut microbiota in rats fed a high fat diet correlate with obesity
      associated metabolic parameters.
AB  - The gut microbiota is emerging as a new factor in the development of obesity.
      Many studies have described changes in microbiota composition in response to
      obesity and high fat diet (HFD) at the phylum level. In this study we used 16s
      RNA high throughput sequencing on faecal samples from rats chronically fed HFD or
      control chow (n = 10 per group, 16 weeks) to investigate changes in gut
      microbiota composition at the species level. 53.17% dissimilarity between groups
      was observed at the species level. Lactobacillus intestinalis dominated the
      microbiota in rats under the chow diet. However this species was considerably
      less abundant in rats fed HFD (P<0.0001), this being compensated by an increase
      in abundance of propionate/acetate producing species. To further understand the
      influence of these species on the development of the obese phenotype, we
      correlated their abundance with metabolic parameters associated with obesity. Of
      the taxa contributing the most to dissimilarity between groups, 10 presented
      significant correlations with at least one of the tested parameters, three of
      them correlated positively with all metabolic parameters: Phascolarctobacterium,
      Proteus mirabilis and Veillonellaceae, all propionate/acetate producers.
      Lactobacillus intestinalis was the only species whose abundance was negatively
      correlated with change in body weight and fat mass. This species decreased
      drastically in response to HFD, favouring propionate/acetate producing bacterial
      species whose abundance was strongly correlated with adiposity and deterioration
      of metabolic factors. Our observations suggest that these species may play a key
      role in the development of obesity in response to a HFD. 

PMID- 25992555
TI  - Altered HLA Class I Profile Associated with Type A/D Nucleophosmin Mutation
      Points to Possible Anti-Nucleophosmin Immune Response in Acute Myeloid Leukemia.
AB  - Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute
      myeloid leukemia (AML) and the newly generated sequences were suggested to induce
      immune response contributing to the relatively favorable outcome of patients in
      this AML subset. We hypothesized that if an efficient immune response against
      mutated nucleophosmin can be induced in vivo, the individuals expressing HLA
      alleles suitable for presenting NPM-derived peptides should be less prone to
      developing AML associated with NPM1 mutation. We thus compared HLA class I
      frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a
      cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal
      individuals (large datasets available from Allele Frequency Net Database).
      Several HLA allelic groups were found to be depleted in NPMc+ patients, but not
      in NPMwt compared to the normal distribution. The decrease was statistically
      significant for HLA B(*)07, B(*)18, and B(*)40. Furthermore, statistically
      significant advantage in the overall survival was found for patients with mutated
      NPM1 expressing at least one of the depleted allelic groups. The majority of the
      depleted alleles were predicted to bind potent NPM-derived immunopeptides and,
      importantly, these peptides were often located in the unmutated part of the
      protein. Our analysis suggests that individuals expressing specific HLA allelic
      groups are disposed to develop an efficient anti-AML immune response thanks to
      aberrant cytoplasmic localization of the mutated NPM protein.

PMID- 25992556
TI  - Reconstructing the Migratory Behavior and Long-Term Survivorship of Juvenile
      Chinook Salmon under Contrasting Hydrologic Regimes.
AB  - The loss of genetic and life history diversity has been documented across many
      taxonomic groups, and is considered a leading cause of increased extinction risk.
      Juvenile salmon leave their natal rivers at different sizes, ages and times of
      the year, and it is thought that this life history variation contributes to their
      population sustainability, and is thus central to many recovery efforts. However,
      in order to preserve and restore diversity in life history traits, it is
      necessary to first understand how environmental factors affect their expression
      and success. We used otolith (87)Sr/(86)Sr in adult Chinook salmon (Oncorhynchus
      tshawytcha) returning to the Stanislaus River in the California Central Valley
      (USA) to reconstruct the sizes at which they outmigrated as juveniles in a wetter
      (2000) and drier (2003) year. We compared rotary screw trap-derived estimates of
      outmigrant timing, abundance and size with those reconstructed in the adults from
      the same cohort. This allowed us to estimate the relative survival and
      contribution of migratory phenotypes (fry, parr, smolts) to the adult spawning
      population under different flow regimes. Juvenile abundance and outmigration
      behavior varied with hydroclimatic regime, while downstream survival appeared to
      be driven by size- and time-selective mortality. Although fry survival is
      generally assumed to be negligible in this system, >20% of the adult spawners
      from outmigration year 2000 had outmigrated as fry. In both years, all three
      phenotypes contributed to the spawning population, however their relative
      proportions differed, reflecting greater fry contributions in the wetter year
      (23% vs. 10%) and greater smolt contributions in the drier year (13% vs. 44%).
      These data demonstrate that the expression and success of migratory phenotypes
      vary with hydrologic regime, emphasizing the importance of maintaining diversity
      in a changing climate.

PMID- 25992557
TI  - Correction: phytomonas: trypanosomatids adapted to plant environments.

PMID- 25992558
TI  - Physiological and Molecular Mechanisms of Differential Sensitivity of Palmer
      Amaranth (Amaranthus palmeri) to Mesotrione at Varying Growth Temperatures.
AB  - Herbicide efficacy is known to be influenced by temperature, however, underlying
      mechanism(s) are poorly understood. A marked alteration in mesotrione [a 4
      hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor] efficacy on Palmer amaranth
      (Amaranthus palmeri S. Watson) was observed when grown under low- (LT, 25/15 
      degrees C, day/night temperatures) and high (HT, 40/30 degrees  C) temperature
      compared to optimum (OT, 32.5/22.5  degrees C) temperature. Based on plant
      height, injury, and mortality, Palmer amaranth was more sensitive to mesotrione
      at LT and less sensitive at HT compared to OT (ED50 for mortality; 18.5, 52.3,
      and 63.7 g ai ha-1, respectively). Similar responses were observed for leaf
      chlorophyll index and photochemical efficiency of PSII (Fv/Fm). Furthermore,
      mesotrione translocation and metabolism, and HPPD expression data strongly
      supported such variation. Relatively more mesotrione was translocated to
      meristematic regions at LT or OT than at HT. Based on T50 values (time required
      to metabolize 50% of the 14C mesotrione), plants at HT metabolized mesotrione
      faster than those at LT or OT (T50; 13, 21, and 16.5 h, respectively). The
      relative HPPD:CPS (carbamoyl phosphate synthetase) or HPPD:beta-tubulin
      expression in mesotrione-treated plants increased over time in all temperature
      regimes; however, at 48 HAT, the HPPD:beta-tubulin expression was exceedingly
      higher at HT compared to LT or OT (18.4-, 3.1-, and 3.5-fold relative to
      untreated plants, respectively). These findings together with an integrated
      understanding of other interacting key environmental factors will have important
      implications for a predictable approach for effective weed management.

PMID- 25992559
TI  - Revealing Beta-diversity patterns of breeding bird and lizard communities on
      inundated land-bridge islands by separating the turnover and nestedness
      components.
AB  - Beta diversity describes changes in species composition among sites in a region
      and has particular relevance for explaining ecological patterns in fragmented
      habitats. However, it is difficult to reveal the mechanisms if broad sense beta
      diversity indices (i.e. yielding identical values under nestedness and species
      replacement) are used. Partitioning beta diversity into turnover (caused by
      species replacement from site to site) and nestedness-resultant components
      (caused by nested species losses) could provide a unique way to understand the
      variation of species composition in fragmented habitats. Here, we collected
      occupancy data of breeding birds and lizards on land-bridge islands in an
      inundated lake in eastern China. We decomposed beta diversity of breeding bird
      and lizard communities into spatial turnover and nestedness-resultant components
      to assess their relative contributions and respective relationships to
      differences in island area, isolation, and habitat richness. Our results showed
      that spatial turnover contributed more to beta diversity than the nestedness
      resultant component. The degree of isolation had no significant effect on overall
      beta diversity or its components, neither for breeding birds nor for lizards. In
      turn, in both groups the nestedness-resultant component increased with larger
      differences in island area and habitat richness, respectively, while turnover
      component decreased with them. The major difference among birds and lizards was a
      higher relevance of nestedness-resultant dissimilarity in lizards, suggesting
      that they are more prone to local extinctions derived from habitat fragmentation.
      The dominance of the spatial turnover component of beta diversity suggests that
      all islands have potential conservation value for breeding bird and lizard
      communities. 

PMID- 25992560
TI  - Delays before Diagnosis and Initiation of Treatment in Patients Presenting to
      Mental Health Services with Bipolar Disorder.
AB  - BACKGROUND: Bipolar disorder is a significant cause of morbidity and mortality.
      Although existing treatments are effective, there is often a substantial delay
      before diagnosis and treatment initiation. We sought to investigate factors
      associated with the delay before diagnosis of bipolar disorder and the onset of
      treatment in secondary mental healthcare. METHOD: Retrospective cohort study
      using anonymised electronic mental health record data from the South London and
      Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case
      Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012.
      The following predictor variables were analysed in a multivariable Cox regression
      analysis: age, gender, ethnicity, compulsory admission to hospital under the UK
      Mental Health Act, marital status and other diagnoses prior to bipolar disorder.
      The outcomes were time to recorded diagnosis from first presentation to
      specialist mental health services (the diagnostic delay), and time to the start
      of appropriate therapy (treatment delay). RESULTS: The median diagnostic delay
      was 62 days (interquartile range: 17-243) and median treatment delay was 31 days
      (4-122). Compulsory hospital admission was associated with a significant
      reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and
      treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders
      were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33
      0.41) and substance misuse disorders (0.44, 0.31-0.61). Prior diagnosis of
      schizophrenia and psychotic depression were associated with reduced treatment
      delay. CONCLUSIONS: Some individuals experience a significant delay in diagnosis
      and treatment of bipolar disorder after initiation of specialist mental
      healthcare, particularly those who have prior diagnoses of alcohol and substance
      misuse disorders. These findings highlight a need for further study on strategies
      to better identify underlying symptoms and offer appropriate treatment sooner in
      order to facilitate improved clinical outcomes, such as developing specialist
      early intervention services to identify and treat people with bipolar disorder.

PMID- 25992561
TI  - Predicting species' vulnerability in a massively perturbed system: the fishes of
      Lake Turkana, Kenya.
AB  - BACKGROUND AND TROPHIC DIVERSITY STUDY: Lake Turkana is an understudied desert
      lake shared by Kenya and Ethiopia. This system is at the precipice of large-scale
      changes in ecological function due to climate change and economic development
      along its major inflowing river, the Omo River. To anticipate response by the
      fish community to these changes, we quantified trophic diversity for seven
      ecological disparate species (Alestes baremose, Hydrocynus forskalli, Labeo
      horie, Lates niloticus, Oreochromis niloticus, Synodontis schall, and Tilapia
      zillii) using stable isotopes. Based on their marked morphological
      differentiation, we postulated that dietary niches of these species would be
      similar in size but show little overlap. The degree of trophic diversity varied
      greatly among the species studied, refuting our hypothesis regarding dietary
      niche size. Oreochromis niloticus and L. niloticus had the highest trophic
      diversity and significantly larger dietary niches than T. zillii, A. baremose and
      H. forskalli. Low overlap among the dietary niches of the seven species, with the
      exception of the synodontid catfish S. schall, is consistent with our second
      hypothesis. PREDICTING SPECIES' VULNERABILITY: Breeding vulnerability was highest
      among those species with the lowest trophic diversity. We predict that in
      suffering two strikes against them, A. baremose, H. forskalli, T. zillii, and L.
      horie will be most affected by the highly altered Lake Turkana ecosystem and that
      O. niloticus, L. niloticus and S. schall will be least affected. Low
      vulnerability among O. niloticus and L. niloticus is promising for the future of
      the lake's fishery, but the third most important fishery species (L. horie) will
      be highly vulnerable to impending ecosystem change. T. zillii should be treated
      as separate from O. niloticus in the fishery given higher sensitivity and a
      different ecological role. We see potential for expansion of the fishery for S.
      schall but don't recommend the development of a fishery for A. baremose and H.
      forskalli.

PMID- 25992562
TI  - Coral settlement on a highly disturbed equatorial reef system.
AB  - Processes occurring early in the life stages of corals can greatly influence the
      demography of coral populations, and successful settlement of coral larvae that
      leads to recruitment is a critical life history stage for coral reef ecosystems.
      Although corals in Singapore persist in one the world's most anthropogenically
      impacted reef systems, our understanding of the role of coral settlement in the
      persistence of coral communities in Singapore remains limited. Spatial and
      temporal patterns of coral settlement were examined at 7 sites in the southern
      islands of Singapore, using settlement tiles deployed and collected every 3
      months from 2011 to 2013. Settlement occurred year round, but varied
      significantly across time and space. Annual coral settlement was low (~54.72 spat
      m(-2) yr(-1)) relative to other equatorial regions, but there was evidence of
      temporal variation in settlement rates. Peak settlement occurred between March
      May and September-November, coinciding with annual coral spawning periods (March
      April and October), while the lowest settlement occurred from December-February
      during the northeast monsoon. A period of high settlement was also observed
      between June and August in the first year (2011/12), possibly due to some species
      spawning outside predicted spawning periods, larvae settling from other locations
      or extended larval settlement competency periods. Settlement rates varied
      significantly among sites, but spatial variation was relatively consistent
      between years, suggesting the strong effects of local coral assemblages or
      environmental conditions. Pocilloporidae were the most abundant coral spat
      (83.6%), while Poritidae comprised only 6% of the spat, and Acroporidae <1%.
      Other, unidentifiable families represented 10% of the coral spat. These results
      indicate that current settlement patterns are reinforcing the local adult
      assemblage structure ('others'; i.e. sediment-tolerant coral taxa) in Singapore,
      but that the replenishment capacity of Singapore's reefs appears relatively
      constrained, which could lead to less resilient reefs.

PMID- 25992563
TI  - Salvianolic Acid B Ameliorates Lipopolysaccharide-Induced Albumin Leakage from
      Rat Mesenteric Venules through Src-Regulated Transcelluar Pathway and
      Paracellular Pathway.
AB  - Lipopolysaccharide (LPS) causes microvascular barrier disruption, leading to
      albumin leakage from microvessels resulting in a range of disastrous sequels.
      Salvianolic acid B (SalB) is a major water-soluble component derived from Salvia
      miltiorrhiza. Previous studies showed its potential to attenuate microvascular
      barrier dysfunction, but the underlying mechanism is not fully understood. The
      present study was intended to investigate the impact of SalB on endothelial cell
      barrier in vivo in rat mesenteric venules as well as in vitro in human umbilical
      vein endothelial cells (HUVECs), aiming at disclosing the mechanism thereof,
      particularly the role of Src in its action. Male Wistar rats were challenged by
      infusion of LPS (2 mg/kg/h) through left femoral vein for 90 min. SalB (5
      mg/kg/h) was administrated either simultaneously with LPS or 30 min after LPS
      infusion through the left jugular vein. Vesicles in venular walls were observed
      by electron microscopy. HUVECs were incubated with LPS with or without SalB. The
      expression of Zonula occluden-1 (ZO-1), VE-cadherin, caveolin-1 and Src in HUVECs
      was assessed by Western blot and confocal microscopy, binding of SalB to Src was
      measured using Surface Plasmon Resonance and BioLayer Interferometry. Treatment
      with SalB inhibited albumin leakage from rat mesenteric venules and inhibited the
      increase of vesicle number in venular endothelial cells induced by LPS. In
      addition, SalB inhibited the degradation of ZO-1, the phosphorylation and
      redistribution of VE-cadherin, the expression and phosphorylation of caveolin-1,
      and phosphoirylation of Src in HUVECs exposed to LPS. Furthermore, SalB was found
      able to bind to Src. This study demonstrates that protection of SalB against
      microvascular barrier disruption is a process involving both para- and trans
      endothelial cell pathway, and highly suggests Src as the key enzyme for SalB to
      work. 

PMID- 25992565
TI  - Wiki surveys: open and quantifiable social data collection.
AB  - In the social sciences, there is a longstanding tension between data collection
      methods that facilitate quantification and those that are open to unanticipated
      information. Advances in technology now enable new, hybrid methods that combine
      some of the benefits of both approaches. Drawing inspiration from online
      information aggregation systems like Wikipedia and from traditional survey
      research, we propose a new class of research instruments called wiki surveys.
      Just as Wikipedia evolves over time based on contributions from participants, we
      envision an evolving survey driven by contributions from respondents. We develop
      three general principles that underlie wiki surveys: they should be greedy,
      collaborative, and adaptive. Building on these principles, we develop methods for
      data collection and data analysis for one type of wiki survey, a pairwise wiki
      survey. Using two proof-of-concept case studies involving our free and open
      source website www.allourideas.org, we show that pairwise wiki surveys can yield
      insights that would be difficult to obtain with other methods. 

PMID- 25992564
TI  - Neuregulin 1 expression and electrophysiological abnormalities in the Neuregulin
      1 transmembrane domain heterozygous mutant mouse.
AB  - BACKGROUND: The Neuregulin 1 transmembrane domain heterozygous mutant (Nrg1 TM
      HET) mouse is used to investigate the role of Nrg1 in brain function and
      schizophrenia-like behavioural phenotypes. However, the molecular alterations in
      brain Nrg1 expression that underpin the behavioural observations have been
      assumed, but not directly determined. Here we comprehensively characterise mRNA
      Nrg1 transcripts throughout development of the Nrg1 TM HET mouse. In addition, we
      investigate the regulation of high-frequency (gamma) electrophysiological
      oscillations in this mutant mouse to associate molecular changes in Nrg1 with a
      schizophrenia-relevant neurophysiological profile. METHODS: Using exonic probes
      spanning the cysteine-rich, epidermal growth factor (EGF)-like, transmembrane and
      intracellular domain encoding regions of Nrg1, mRNA levels were measured using
      qPCR in hippocampus and frontal cortex from male and female Nrg1 TM HET and wild
      type-like (WT) mice throughout development. We also performed
      electrophysiological recordings in adult mice and analysed gamma oscillatory at
      baseline, in responses to auditory stimuli and to ketamine. RESULTS: In both
      hippocampus and cortex, Nrg1 TM HET mice show significantly reduced expression of
      the exon encoding the transmembrane domain of Nrg1 compared with WT, but
      unaltered mRNA expression encoding the extracellular bioactive EGF-like and the
      cysteine-rich (type III) domains, and development-specific and region-specific
      reductions in the mRNA encoding the intracellular domain. Hippocampal Nrg1
      protein expression was not altered, but NMDA receptor NR2B subunit
      phosphorylation was lower in Nrg1 TM HET mice. We identified elevated ongoing and
      reduced sensory-evoked gamma power in Nrg1 TM HET mice. INTERPRETATION: We found
      no evidence to support the claim that the Nrg1 TM HET mouse represents a simple
      haploinsufficient model. Further research is required to explore the possibility
      that mutation results in a gain of Nrg1 function.

PMID- 25992567
TI  - Respective and combined effects of impairments in sensorimotor systems and
      cognition on gait performance: a population-based cross-sectional study.
AB  - BACKGROUND: Respective and combined effects of impairments in sensorimotor
      systems and cognition on gait performance have not been fully studied. This study
      aims to describe the respective effects of impairments in muscle strength,
      distance vision, lower-limb proprioception and cognition on the Timed Up & Go
      (TUG) scores (i.e., performed TUG [pTUG], imagined TUG [iTUG] and the time
      difference between these two tests [delta TUG]) in older community-dwellers; and
      to examine their combined effects on TUG scores. METHODS: Based on a cross
      sectional design, 1792 community-dwellers (70.2 +/- 4.8 years; 53.6% female) were
      recruited. Gait performance was assessed using pTUG, iTUG and delta TUG.
      Participants were divided into healthy individuals and 15 subgroups of
      individuals according to the presence of impairment in one or more subsystems
      involved in gait control (i.e., muscle strength and/or distance vision and/or
      lower-limb proprioception and/or cognition [episodic memory and executive
      performance]). Impairment in muscle strength, distance vision and lower-limb
      proprioception was defined as being in the lowest tertile of performance.
      Impairment in cognition was defined as abnormal episodic memory and executive
      tests. RESULTS: A total of 191 (10.7%) exhibited impairment in muscle strength,
      188 (10.5%) in distance vision, 302 (16.9%) in lower-limb proprioception, and 42
      (2.3%) in cognition. Linear regressions showed that cognitive impairment as well
      as dual combinations of impairments were associated with increased pTUG (P<0.02).
      Impairment in lower-limb proprioception was associated with decreased iTUG
      (P=0.015). All combinations of impairments, except those including muscle
      strength and the combinations of the 4 subsystems, were associated with increased
      delta TUG (P<0.04). CONCLUSION: Cognitive integrity is central for efficient gait
      control and stability, whereas lower-limb proprioception seems to be central for
      gait imagery.

PMID- 25992566
TI  - Impact of Psychopathy on Moral Judgments about Causing Fear and Physical Harm.
AB  - Psychopathy is a personality variable associated with persistent immoral
      behaviors. Despite this, attempts to link moral reasoning deficits to
      psychopathic traits have yielded mixed results with many findings supporting
      intact moral reasoning in individuals with psychopathic traits. Abundant evidence
      shows that psychopathy impairs responses to others' emotional distress. However,
      most studies of morality and psychopathy focus on judgments about causing others
      physical harm. Results of such studies may be inconsistent because physical harm
      is an imperfect proxy for emotional distress. No previous paradigm has explicitly
      separated judgments about physical harm and emotional distress and assessed how
      psychopathy affects each type of judgment. In three studies we found that
      psychopathy impairs judgments about causing others emotional distress
      (specifically fear) but minimally affects judgments about causing physical harm
      and that judgments about causing fear predict instrumental aggression in
      psychopathy. These findings are consistent with reports linking psychopathy to
      insensitivity to others' fear, and suggest that sensitivity to others' fear may
      play a fundamental role in the types of moral decision-making impaired by
      psychopathy. 

PMID- 25992568
TI  - Type and timing of childhood maltreatment and severity of shutdown dissociation
      in patients with schizophrenia spectrum disorder.
AB  - Dissociation, particularly the shutting down of sensory, motor and speech
      systems, has been proposed to emerge in susceptible individuals as a defensive
      response to traumatic stress. In contrast, other individuals show signs of
      hyperarousal to acute threat. A key question is whether exposure to particular
      types of stressful events during specific stages of development can program an
      individual to have a strong dissociative response to subsequent stressors.
      Vulnerability to ongoing shutdown dissociation was assessed in 75 inpatients (46
      M/29 F, M = 31 +/- 10 years old) with schizophrenia spectrum disorder and related
      to number of traumatic events experienced or witnessed during childhood or
      adulthood. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was
      used to collect retrospective recall of exposure to ten types of maltreatment
      during each year of childhood. Severity of shutdown dissociation was related to
      number of childhood but not adult traumatic events. Random forest regression with
      conditional trees indicated that type and timing of childhood maltreatment could
      predictably account for 31% of the variance (p < 0.003) in shutdown dissociation,
      with peak vulnerability occurring at 13-14 years of age and with exposure to
      emotional neglect followed by various forms of emotional abuse. These findings
      suggest that there may be windows of vulnerability to the development of shutdown
      dissociation. Results support the hypothesis that experienced events are more
      important than witnessed events, but challenge the hypothesis that "life
      threatening" events are a critical determinant.

PMID- 25992569
TI  - Is Social Capital a Determinant of Oral Health among Older Adults? Findings from
      the English Longitudinal Study of Ageing.
AB  - There are a number of studies linking social capital to oral health among older
      adults, although the evidence base mainly relies on cross-sectional study
      designs. The possibility of reverse causality is seldom discussed, even though
      oral health problems could potentially lead to lower social participation.
      Furthermore, few studies clearly distinguish between the effects of different
      dimensions of social capital on oral health. The objective of the study was to
      examine the longitudinal associations between individual social capital and oral
      health among older adults. We analyzed longitudinal data from the 3rd and 5th
      waves of the English Longitudinal Study of Ageing (ELSA). Structural social
      capital was operationalized using measures of social participation, and
      volunteering. Number of close ties and perceived emotional support comprised the
      functional dimension of social capital. Oral health measures were having no
      natural teeth (edentate vs. dentate), self-rated oral health and oral health
      related quality of life. Time-lag and autoregressive models were used to explore
      the longitudinal associations between social capital and oral health. We imputed
      all missing data, using multivariate imputation by chained equations. We found
      evidence of bi-directional longitudinal associations between self-rated oral
      health, volunteering and functional social capital. Functional social capital was
      a strong predictor of change in oral health-related quality of life - the
      adjusted odds ratio of reporting poor oral health-related quality of life was
      1.75 (1.33-2.30) for older adults with low vs. high social support. However in
      the reverse direction, poor oral health-related quality of life was not
      associated with changes in social capital. This suggests that oral health may not
      be a determinant of social capital. In conclusion, social capital may be a
      determinant of subjective oral health among older adults rather than
      edentulousness, despite many cross-sectional studies on the latter. 

PMID- 25992571
TI  - Freezing behavior as a response to sexual visual stimuli as demonstrated by
      posturography.
AB  - Posturographic changes in motivational conditions remain largely unexplored in
      the context of embodied cognition. Over the last decade, sexual motivation has
      been used as a good canonical working model to study motivated social
      interactions. The objective of this study was to explore posturographic
      variations in response to visual sexual videos as compared to neutral videos. Our
      results support demonstration of a freezing-type response in response to sexually
      explicit stimuli compared to other conditions, as demonstrated by significantly
      decreased standard deviations for (i) the center of pressure displacement along
      the mediolateral and anteroposterior axes and (ii) center of pressure's
      displacement surface. These results support the complexity of the motor
      correlates of sexual motivation considered to be a canonical functional context
      to study the motor correlates of motivated social interactions. 

PMID- 25992570
TI  - Prognostic value of obesity on both overall mortality and cardiovascular disease
      in the general population.
AB  - BACKGROUND: Obesity represents an important health problem and its association
      with cardiovascular risk factors is well-known. The aim of this work was to
      assess the correlation between obesity and mortality (both, all-cause mortality
      and the combined variable of all-cause mortality plus the appearance of a non
      fatal first cardiovascular event) in a general population sample from the south
      east of Spain. MATERIALS AND METHODS: This prospective cohort study used
      stratified and randomized two-stage sampling. Obesity [body mass index (BMI) >=
      30 kg/m(2)] as a predictive variable of mortality and cardiovascular events was
      assessed after controlling for age, sex, cardiovascular disease history, high
      blood pressure, diabetes mellitus, hypercholesterolemia, high-density
      lipoprotein/triglycerides ratio, total cholesterol and smoking with the Cox
      regression model. RESULTS: The mean follow-up time of the 1,248 participants was
      10.6 years. The incidence of all-cause mortality during this period was 97 deaths
      for every 10,000 person/years (95% CI: 80-113) and the incidence of all-cause
      mortality+cardiovascular morbidity was 143 cases for every 10,000 person/years
      (95% CI: 124-163). A BMI >= 35 kg/m(2) yielded a hazard ratio for all-cause
      mortality of 1.94 (95% CI: 1.11-3.42) in comparison to non-obese subjects (BMI
      <30 kg/m(2)). For the combination of cardiovascular morbidity plus all-cause
      mortality, a BMI >= 35 kg/m(2) had a hazard ratio of 1.84 (95% CI: 1.15-2.93)
      compared to non-obese subjects. CONCLUSIONS: A BMI >= 35 kg/m(2) is an important
      predictor of both overall mortality and of the combination of cardiovascular
      morbidity plus all-cause mortality.

PMID- 25992572
TI  - Benthic Assemblages of the Anton Dohrn Seamount (NE Atlantic): Defining Deep-Sea
      Biotopes to Support Habitat Mapping and Management Efforts with a Focus on
      Vulnerable Marine Ecosystems.
AB  - In 2009 the NW and SE flanks of Anton Dohrn Seamount were surveyed using
      multibeam echosounder and video ground-truthing to characterise megabenthic
      biological assemblages (biotopes) and assess those which clearly adhere to the
      definition of Vulnerable Marine Ecosystems, for use in habitat mapping. A
      combination of multivariate analysis of still imagery and video ground-truthing
      defined 13 comprehensive descriptions of biotopes that function as mapping units
      in an applied context. The data reveals that the NW and SE sides of Anton Dohrn
      Seamount (ADS) are topographically complex and harbour diverse biological
      assemblages, some of which agree with current definitions of 'listed' habitats of
      conservation concern. Ten of these biotopes could easily be considered Vulnerable
      Marine Ecosystems; three coral gardens, four cold-water coral reefs, two
      xenophyophore communities and one sponge dominated community, with remaining
      biotopes requiring more detailed assessment. Coral gardens were only found on
      positive geomorphic features, namely parasitic cones and radial ridges, found
      both sides of the seamount over a depth of 1311-1740 m. Two cold-water coral
      reefs (equivalent to summit reef) were mapped on the NW side of the seamount;
      Lophelia pertusa reef associated with the cliff top mounds at a depth of 747-791
      m and Solenosmilia variabilis reef on a radial ridge at a depth of 1318-1351 m.
      Xenophyophore communities were mapped from both sides of the seamount at a depth
      of 1099-1770 m and were either associated with geomorphic features or were in
      close proximity (< 100 m) to them. The sponge dominated community was found on
      the steep escarpment either side of the seamount over at a depth of 854-1345 m.
      Multivariate diversity revealed the xenophyophore biotopes to be the least
      diverse, and a hard substratum biotope characterised by serpulids and the sessile
      holothurian, Psolus squamatus, as the most diverse. 

PMID- 25992573
TI  - "I have no clue what I drunk last night" using Smartphone technology to compare
      in-vivo and retrospective self-reports of alcohol consumption.
AB  - AIM: This research compared real-time measurements of alcohol consumption with
      retrospective accounts of alcohol consumption to examine possible discrepancies
      between, and contextual influences on, the different accounts. METHOD: Building
      on previous investigations, a specifically designed Smartphone technology was
      utilized to measure alcohol consumption and contextual influences in de facto
      real-time. Real-time data (a total of 10,560 data points relating to type and
      number of drinks and current social / environmental context) were compared with
      daily and weekly retrospective accounts of alcohol consumption. RESULTS:
      Participants reported consuming more alcoholic drinks during real-time assessment
      than retrospectively. For daily accounts a higher number of drinks consumed in
      real-time was related to a higher discrepancy between real-time and retrospective
      accounts. This effect was found across all drink types but was not shaped by
      social and environmental contexts. Higher in-vivo alcohol consumption appeared to
      be related to a higher discrepancy in retrospectively reported weekly consumption
      for alcohol beverage types other than wine. When including contextual factors
      into the statistical models, being with two or more friends (as opposed to being
      alone) decreased the discrepancy between real-time and retrospective reports,
      whilst being in the pub (relative to being at home) was associated with greater
      discrepancies. CONCLUSIONS: Overall, retrospective accounts may underestimate the
      amount of actual, real-time alcohol consumed. Increased consumption may also
      exacerbate differences between real-time and retrospective accounts. Nonetheless,
      this is not a global effect as environmental and social contexts interact with
      the type of alcohol consumed and the time frame given for reporting (weekly vs.
      daily retrospective). A degree of caution therefore appears warranted with
      regards to the use of retrospective self-report methods of recording alcohol
      consumption. Whilst real-time sampling is unlikely to be completely error free,
      it may be better able to account for social and environmental influences on self
      reported consumption.

PMID- 25992574
TI  - Correction: Rhizodeposition of Nitrogen and Carbon by Mungbean (Vigna radiata L.)
      and Its Contribution to Intercropped Oats (Avena nuda L.).

PMID- 25992575
TI  - Reduced bacterial colony count of anaerobic bacteria is associated with a
      worsening in lung clearance index and inflammation in cystic fibrosis.
AB  - Anaerobic bacteria have been identified in abundance in the airways of cystic
      fibrosis (CF) subjects. The impact their presence and abundance has on lung
      function and inflammation is unclear. The aim of this study was to investigate
      the relationship between the colony count of aerobic and anaerobic bacteria, lung
      clearance index (LCI), spirometry and C-Reactive Protein (CRP) in patients with
      CF. Sputum and blood were collected from CF patients at a single cross-sectional
      visit when clinically stable. Community composition and bacterial colony counts
      were analysed using extended aerobic and anaerobic culture. Patients completed
      spirometry and a multiple breath washout (MBW) test to obtain LCI. An inverse
      correlation between colony count of aerobic bacteria (n = 41, r = -0.35; p =
      0.02), anaerobic bacteria (n = 41, r = -0.44, p = 0.004) and LCI was observed.
      There was an inverse correlation between colony count of anaerobic bacteria and
      CRP (n = 25, r = -0.44, p = 0.03) only. The results of this study demonstrate
      that a lower colony count of aerobic and anaerobic bacteria correlated with a
      worse LCI. A lower colony count of anaerobic bacteria also correlated with higher
      CRP levels. These results indicate that lower abundance of aerobic and anaerobic
      bacteria may reflect microbiota disruption and disease progression in the CF
      lung. 

PMID- 25992576
TI  - Multimodal distribution of human cold pain thresholds.
AB  - BACKGROUND: It is assumed that different pain phenotypes are based on varying
      molecular pathomechanisms. Distinct ion channels seem to be associated with the
      perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted
      previously. The present study analyzed the distribution of cold pain thresholds
      with focus at describing the multimodality based on the hypothesis that it
      reflects a contribution of distinct ion channels. METHODS: Cold pain thresholds
      (CPT) were available from 329 healthy volunteers (aged 18 - 37 years; 159 men)
      enrolled in previous studies. The distribution of the pooled and log-transformed
      threshold data was described using a kernel density estimation (Pareto Density
      Estimation (PDE)) and subsequently, the log data was modeled as a mixture of
      Gaussian distributions using the expectation maximization (EM) algorithm to
      optimize the fit. RESULTS: CPTs were clearly multi-modally distributed. Fitting a
      Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that
      the best fit is obtained when applying a three-model distribution pattern. The
      modes of the identified three Gaussian distributions, retransformed from the log
      domain to the mean stimulation temperatures at which the subjects had indicated
      pain thresholds, were obtained at 23.7  degrees C, 13.2  degrees C and 1.5 
      degrees C for Gaussian #1, #2 and #3, respectively. CONCLUSIONS: The localization
      of the first and second Gaussians was interpreted as reflecting the contribution
      of two different cold sensors. From the calculated localization of the modes of
      the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing
      temperatures from 25 - 24  degrees C, and TRPA1, sensing cold from 17  degrees C
      can be derived. In that case, subjects belonging to either Gaussian would possess
      a dominance of the one or the other receptor at the skin area where the cold
      stimuli had been applied. The findings therefore support a suitability of complex
      analytical approaches to detect mechanistically determined patterns from pain
      phenotype data.

PMID- 25992577
TI  - Isolation and characterisation of mesenchymal stem/stromal cells in the ovine
      endometrium.
AB  - OBJECTIVE: Mesenchymal stem/stromal cells (MSC) were recently discovered in the
      human endometrium. These cells possess key stem cell properties and show
      promising results in small animal models when used for preclinical tissue
      engineering studies. A small number of surface markers have been identified that
      enrich for MSC from bone marrow and human endometrium, including the Sushi Domain
      containing 2 (SUSD2; W5C5) and CD271 markers. In preparation for developing a
      large animal preclinical model for urological and gynecological tissue
      engineering applications we aimed to identify and characterise MSC in ovine
      endometrium and determine surface markers to enable their prospective isolation.
      MATERIALS AND METHODS: Ovine endometrium was obtained from hysterectomised ewes
      following progesterone synchronisation, dissociated into single cell suspensions
      and tested for MSC surface markers and key stem cell properties. Purified stromal
      cells were obtained by flow cytometry sorting with CD49f and CD45 to remove
      epithelial cells and leukocytes respectively, and MSC properties investigated.
      RESULTS: There was a small population CD271+ stromal cells (4.5 +/- 2.3%) in the
      ovine endometrium. Double labelling with CD271 and CD49f showed that the sorted
      CD271+CD49f- stromal cell population possessed significantly higher cloning
      efficiency, serial cloning capacity and a qualitative increased ability to
      differentiate into 4 mesodermal lineages (adipocytic, smooth muscle, chondrocytic
      and osteoblastic) than CD271-CD49f- cells. Immunolabelling studies identified an
      adventitial perivascular location for ovine endometrial CD271+ cells. CONCLUSION:
      This is the first study to characterise MSC in the ovine endometrium and identify
      a surface marker profile identifying their location and enabling their
      prospective isolation. This knowledge will allow future preclinical studies with
      a large animal model that is well established for pelvic organ prolapse research.

PMID- 25992578
TI  - Does Environmental Instability Favor the Production and Horizontal Transmission
      of Knowledge regarding Medicinal Plants? A Study in Southeast Brazil.
AB  - Greater socio-environmental instability favors the individual production of
      knowledge because innovations are adapted to new circumstances. Furthermore,
      instability stimulates the horizontal transmission of knowledge because this
      mechanism disseminates adapted information. This study investigates the following
      hypothesis: Greater socio-environmental instability favors the production of
      knowledge (innovation) to adapt to new situations, and socio-environmental
      instability stimulates the horizontal transmission of knowledge, which is a
      mechanism that diffuses adapted information. In addition, the present study
      describes "how", "when", "from whom" and the "stimulus/context", in which
      knowledge regarding medicinal plants is gained or transferred. Data were
      collected through semi-structured interviews from three groups that represented
      different levels of socio-environmental instability. Socio-environmental
      instability did not favor individual knowledge production or any cultural
      transmission modes, including vertical to horizontal, despite increasing the
      frequency of horizontal pathways. Vertical transmission was the most important
      knowledge transmission strategy in all of the groups in which mothers were the
      most common models (knowledge sources). Significantly, childhood was the most
      important learning stage, although learning also occurred throughout life. Direct
      teaching using language was notable as a knowledge transmission strategy. Illness
      was the main stimulus that triggered local learning. Learning modes about
      medicinal plants were influenced by the knowledge itself, particularly the
      dynamic uses of therapeutic resources. 

PMID- 25992579
TI  - Application of hierarchical dissociated neural network in closed-loop hybrid
      system integrating biological and mechanical intelligence.
AB  - Neural networks are considered the origin of intelligence in organisms. In this
      paper, a new design of an intelligent system merging biological intelligence with
      artificial intelligence was created. It was based on a neural controller
      bidirectionally connected to an actual mobile robot to implement a novel vehicle.
      Two types of experimental preparations were utilized as the neural controller
      including 'random' and '4Q' (cultured neurons artificially divided into four
      interconnected parts) neural network. Compared to the random cultures, the '4Q'
      cultures presented absolutely different activities, and the robot controlled by
      the '4Q' network presented better capabilities in search tasks. Our results
      showed that neural cultures could be successfully employed to control an
      artificial agent; the robot performed better and better with the stimulus because
      of the short-term plasticity. A new framework is provided to investigate the
      bidirectional biological-artificial interface and develop new strategies for a
      future intelligent system using these simplified model systems. 

PMID- 25992580
TI  - Correction: A Bundle of Services Increased Ascertainment of Tuberculosis among
      HIV-Infected Individuals Enrolled in a HIV Cohort in Rural Sub-Saharan Africa.

PMID- 25992581
TI  - Natural killer cells promote long-term hepatobiliary inflammation in a low-dose
      rotavirus model of experimental biliary atresia.
AB  - Biliary atresia is a rapidly progressive obstructive cholangiopathy of infants.
      Mechanistic studies in the mouse model of Rhesus rotavirus (RRV)-induced biliary
      atresia have linked the importance of effector lymphocytes to the pathogenesis of
      extrahepatic bile duct (EHBD) injury and obstruction in experimental biliary
      atresia; however, studies of the progressive liver injury have been limited by
      early death of newborn mice. Here, we aimed to determine 1) if a lower inoculum
      of RRV induces obstruction of EHBDs while allowing for ongoing liver
      inflammation, and 2) if NK cells regulate intrahepatic injury. The administration
      of 0.25 x 10(6) fluorescence forming units of RRV induced an obstructive
      extrahepatic cholangiopathy, but allowed for restoration of the duct epithelium,
      increased survival, and the development of a progressive intrahepatic
      inflammatory injury with molecular and cellular signatures equivalent to the
      traditional infectious model. Investigating the mechanisms of liver injury, we
      found that NK cell depletion at the onset of jaundice decreased liver
      inflammation, suppressed the expression of fibrosis and inflammation/immunity
      genes, lowered plasma ALT and bilirubin and improved survival. CONCLUSIONS: Lower
      inoculation of RRV-induced progressive liver injury and fibrosis via NK cells.
      These findings point to the potential use of NK cell-depleting strategies to
      block progression of liver disease in biliary atresia.

PMID- 25992582
TI  - Antibacterial Compounds from Propolis of Tetragonula laeviceps and Tetrigona
      melanoleuca (Hymenoptera: Apidae) from Thailand.
AB  - This study investigated the chemical composition and antimicrobial activity of
      propolis collected from two stingless bee species Tetragonula laeviceps and
      Tetrigona melanoleuca (Hymenoptera: Apidae). Six xanthones, one triterpene and
      one lignane were isolated from Tetragonula laeviceps propolis. Triterpenes were
      the main constituents in T. melanoleuca propolis. The ethanol extract and
      isolated compounds from T. laeviceps propolis showed a higher antibacterial
      activity than those of T. melanoleuca propolis as the constituent alpha-mangostin
      exhibited the strongest activity. Xanthones were found in propolis for the first
      time; Garcinia mangostana (Mangosteen) was the most probable plant source. In
      addition, this is the first report on the chemical composition and bioactivity of
      propolis from T. melanoleuca. 

PMID- 25992583
TI  - Technique of porcine liver procurement and orthotopic transplantation using an
      active porto-caval shunt.
AB  - The success of liver transplantation has resulted in a dramatic organ shortage.
      Each year, a considerable number of patients on the liver transplantation waiting
      list die without receiving an organ transplant or are delisted due to disease
      progression. Even after a successful transplantation, rejection and side effects
      of immunosuppression remain major concerns for graft survival and patient
      morbidity. Experimental animal research has been essential to the success of
      liver transplantation and still plays a pivotal role in the development of
      clinical transplantation practice. In particular, the porcine orthotopic liver
      transplantation model (OLTx) is optimal for clinically oriented research for its
      close resemblance to human size, anatomy, and physiology. Decompression of
      intestinal congestion during the anhepatic phase of porcine OLTx is important to
      guarantee reliable animal survival. The use of an active porto-caval-jugular
      shunt achieves excellent intestinal decompression. The system can be used for
      short-term as well as long-term survival experiments. The following protocol
      contains all technical information for a stable and reproducible liver
      transplantation model in pigs including post-operative animal care. 

PMID- 25992584
TI  - Oxygen-glucose deprivation and reoxygenation as an in vitro ischemia-reperfusion
      injury model for studying blood-brain barrier dysfunction.
AB  - Ischemia-Reperfusion (IR) injury is known to contribute significantly to the
      morbidity and mortality associated with ischemic strokes. Ischemic
      cerebrovascular accidents account for 80% of all strokes. A common cause of IR
      injury is the rapid inflow of fluids following an acute/chronic occlusion of
      blood, nutrients, oxygen to the tissue triggering the formation of free radicals.
      Ischemic stroke is followed by blood-brain barrier (BBB) dysfunction and
      vasogenic brain edema. Structurally, tight junctions (TJs) between the
      endothelial cells play an important role in maintaining the integrity of the
      blood-brain barrier (BBB). IR injury is an early secondary injury leading to a
      non-specific, inflammatory response. Oxidative and metabolic stress following
      inflammation triggers secondary brain damage including BBB permeability and
      disruption of tight junction (TJ) integrity. Our protocol presents an in vitro
      example of oxygen-glucose deprivation and reoxygenation (OGD-R) on rat brain
      endothelial cell TJ integrity and stress fiber formation. Currently, several
      experimental in vivo models are used to study the effects of IR injury; however
      they have several limitations, such as the technical challenges in performing
      surgeries, gene dependent molecular influences and difficulty in studying
      mechanistic relationships. However, in vitro models may aid in overcoming many of
      those limitations. The presented protocol can be used to study the various
      molecular mechanisms and mechanistic relationships to provide potential
      therapeutic strategies. However, the results of in vitro studies may differ from
      standard in vivo studies and should be interpreted with caution. 

PMID- 25992585
TI  - Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age
      Acute Leukemia.
AB  - Based on observational studies, early age leukemia (EAL) was associated with
      maternal hormone exposure during pregnancy. We studied the association between
      genetic polymorphisms of estrogen metabolism and EAL. Using data from the
      Brazilian Collaborative Study Group of Infant Acute Leukemia (2000-2012), 350
      cases and 404 age-matched controls and 134 mothers of cases and controls were
      genotyped to explore polymorphisms in genes of the estrogen metabolism pathway:
      CYP1B1 (c.1294C>G, rs1056836), CYP3A4 (c.-392A>G, rs2740574), CYP3A5 (c.219
      237G>A, rs776746), GSTM1/GSTT1 deletions, and SULT1A1 (c.638G>A, rs9282861; and
      c.667A>G, rs1801030). Logistic regression was used to calculate the odds ratios
      (OR) with 95% confidence intervals (CIs), and unconditional logistic regression
      was used to estimate adjusted odds ratios (aORs) by ethnicity. Because of
      multiple testing, p values < 0.01 were significant after Bonferroni correction.
      SULT1A1 (c.638G>A) was associated to infant acute lymphoblastic leukemia and
      acute myeloid leukemia (AML) risk in males (additive model: aOR = 0.52; 95% CI:
      0.29-0.95, p = 0.03; dominant model: aOR = 2.18; 95% CI: 1.17-4.05, p = 0.01,
      respectively). CYP1B1 polymorphism was associated with a decreased risk of AML
      either for non-white or female children (additive model: OR = 0.24; 95% CI: 0.08
      0.76, p < 0.01; additive model: aOR = 0.27; 95% CI: 0.08-0.89, p = 0.03,
      respectively). Since polymorphisms of Cytochrome P450 genes presented gender
      specific risk associations, we also investigated their expression. CYP1B1 was not
      expressed in 57.1% of EAL cases, and its expression varied by genotype, gender,
      and leukemia subtype. Maternal-fetal GSTT1 null genotype was associated with risk
      of EAL. This study shows that polymorphisms in genes of estrogen metabolism
      confer genetic susceptibility to EAL, mainly in males, and maternal
      susceptibility genes modify the risk for developing EAL in newborns. 

PMID- 25992586
TI  - Testing for odor discrimination and habituation in mice.
AB  - This video demonstrates a technique to establish the presence of a normally
      functioning olfactory system in a mouse. The test helps determine whether the
      mouse can discriminate between non-social odors and social odors, whether the
      mouse habituates to a repeatedly presented odor, and whether the mouse
      demonstrates dishabituation when presented with a novel odor. Since many social
      behavior tests measure the experimental animal's response to a familiar or novel
      mouse, false positives can be avoided by establishing that the animals can detect
      and discriminate between social odors. There are similar considerations in
      learning tests such as fear conditioning that use odor to create a novel
      environment or olfactory cues as an associative stimulus. Deficits in the
      olfactory system would impair the ability to distinguish between contexts and to
      form an association with an olfactory cue during fear conditioning. In the odor
      habitation/dishabituation test, the mouse is repeatedly presented with several
      odors. Each odor is presented three times for two minutes. The investigator
      records the sniffing time directed towards the odor as the measurement of
      olfactory responsiveness. A typical mouse shows a decrease in response to the
      odor over repeated presentations (habituation). The experimenter then presents a
      novel odor that elicits increased sniffing towards the new odor (dishabituation).
      After repeated presentation of the novel odor the animal again shows habituation.
      This protocol involves the presentation of water, two or more non-social odors,
      and two social odors. In addition to reducing experimental confounds, this test
      can provide information on the function of the olfactory systems of new knockout,
      knock-in, and conditional knockout mouse lines. 

PMID- 25992587
TI  - An equation describing diffusivity of liquid atoms by magnetic confinement.
AB  - In this work, we report an obvious low field-induced magnetic confinement effect
      on the diffusivity in binary metallic melts under a weak magnetic field. A
      quantitative description of this nontrivial dynamic behavior is given by a
      physical analytical model based on the Hall effect, which is in agreement with
      our experimental results. Meanwhile, a quadratic B dependence of the dynamic
      viscosity obtained in the same confined environment is observed. Our results show
      that one can effectively control the atomic diffusion process of metallic melts
      by the application of magnetic field. Meanwhile, this magnetic confinement effect
      at atomic scale should provide an important new ingredient to deeply understand
      the condensed matter physics under the external magnetic field. 

PMID- 25992588
TI  - Conformational gating dynamics in the GluCl anion-selective chloride channel.
AB  - Cys-loop receptors are central to propagation of signals in the nervous system.
      The gating of the membrane-spanning pore is triggered by structural
      rearrangements in the agonist-binding site, located some 50 A away from the pore.
      A sequential conformational change, propagating from the ligand-binding site to
      the pore, has been proposed to govern gating in all Cys-loop receptors. Here, we
      identify structural and dynamic components of the conformational gating in the
      eukaryotic glutamate-gated chloride channel (GluCl) by means of molecular
      dynamics (MD) simulations with and without the l-glutamate agonist bound. A
      significant increase in pore opening and accompanying hydration is observed in
      the presence of glutamate. Potential of mean force calculations reveal that the
      barrier for ion passage drops from 15 kcal/mol to 5-10 kcal/mol with the agonist
      bound. This appears to be explained by agonist binding that leads to significant
      changes in the intersubunit hydrogen-bonding pattern, which induce a slight tilt
      of the extracellular domain relative to the transmembrane domain in the
      simulations. This rearrangement is subtle, but correspond to the direction of the
      quaternary twist observed as a key difference between open and closed X-ray
      structures. While the full reversible gating is still a much slower process, the
      observed structural dynamics sheds new light on the early stages of how the
      agonist influences the extracellular domain, how the extracellular domain
      interacts with the transmembrane domain, and how changes in the transmembrane
      domain alter the free energy of ion passage. 

PMID- 25992590
TI  - Friction and Wear Properties of Different Types of Graphene Nanosheets as
      Effective Solid Lubricants.
AB  - Friction and wear properties of graphene nanosheets prepared by different
      processes as solid lubricant on silicon dioxide have been comparatively studied
      via calibrated atomic force microscopy. The effects of normal load, humidity, and
      velocity on the friction were also investigated. All kinds of graphene nanosheets
      possess friction-reduction properties on the nanoscale. Mechanically exfoliated
      graphene nanosheets exhibit ultralubrication and zero wear under high pressure
      due to perfect graphitic structure and a hydrophobic surface. Defects in chemical
      vapor deposited graphene nanosheets decrease the antiwear and friction-reduction
      capability. The graphene oxide nanosheets (GOS) show the weakest friction
      reduction properties on account of destroyed graphitic structure and a
      hydrophilic surface. The reduced graphene oxide nanosheets (RGOS) possess better
      friction reduction than GOS by virtue of hydrophobic surface properties. Both
      RGOS and GOS have weak antiwear properties due to the destroyed graphitic
      structure. Antiwear properties are correlated strongly with the structure, and
      friction depends mainly on the structure and surface properties. 

PMID- 25992589
TI  - GREM1 germline mutation screening in Ashkenazi Jewish patients with familial
      colorectal cancer.
AB  - BACKGROUND: A 40 kb ancestral germline duplication upstream of the GREM1 gene was
      reported in Ashkenazi families with hereditary mixed polyposis syndrome (HMPS).
      OBJECTIVE: Assess the contribution of the GREM1 mutation to familial colorectal
      cancer (CRC) in Ashkenazim. METHODS: Jewish Ashkenazi individuals (n = 472 155
      males, 317 females) were genotyped for the GREM1 duplication, 194 with CRC, 131
      had other cancer types (endometrial, pancreatic and ovarian) that show a
      syndromic association with CRC, and 147 were cancer-free with a suggestive family
      history of CRC. RESULTS: One mutation carrier was found who fulfills the
      Amsterdam criteria for Lynch Syndrome (LS). The prevalence of this mutation
      amongst LS Ashkenazim is 0.7%. CONCLUSION: If validated in additional studies it
      seems rational to recommend to look for the GREM1 founder mutation in Ashkenazi
      individuals with multiple colorectal polyps and/or fulfill the criteria for LS.

PMID- 25992591
TI  - Facile Rh(III)-Catalyzed Synthesis of Fluorinated Pyridines.
AB  - A Rh(III)-catalyzed C-H functionalization approach was developed for the
      preparation of multisubstituted 3-fluoropyridines from alpha-fluoro-alpha,beta
      unsaturated oximes and alkynes. Oximes substituted with aryl, heteroaryl, and
      alkyl beta-substituents were effective coupling partners, as were symmetrical and
      unsymmetrical alkynes with aryl and alkyl substituents. The first examples of
      coupling alpha,beta-unsaturated oximes with terminal alkynes was also
      demonstrated and proceeded with uniformly high regioselectivity to provide single
      3-fluoropyridine regioisomers. Reactions were also conveniently set up in air on
      the benchtop. 

PMID- 25992592
TI  - Effects of increasing nitrogen and phosphorus concentrations on phytoplankton
      community growth and toxicity during Planktothrix blooms in Sandusky Bay, Lake
      Erie.
AB  - Sandusky Bay experiences annual toxic cyanobacterial blooms dominated by
      Planktothrix agardhii/suspensa. To further understand the environmental drivers
      of these events, we evaluated changes in the growth response and toxicity of the
      Planktothrix-dominated blooms to nutrient amendments with orthophosphate (PO4)
      and inorganic and organic forms of dissolved nitrogen (N; ammonium (NH4), nitrate
      (NO3) and urea) over the bloom season (June - October). We complemented these
      with a metagenomic analysis of the planktonic microbial community. Our results
      showed that bloom growth and microcystin (MC) concentrations responded more
      frequently to additions of dissolved N than PO4, and that the dual addition of
      NH4 + PO4 and Urea + PO4 yielded the highest MC concentrations in 54% of
      experiments. Metagenomic analysis confirmed that P. agardhii/suspensa was the
      primary MC producer. The phylogenetic distribution of nifH revealed that both
      heterocystous cyanobacteria and heterotrophic proteobacteria had the genetic
      potential for N2 fixation in Sandusky Bay. These results suggest that as best
      management practices are developed for P reductions in Sandusky Bay, managers
      must be aware of the negative implications of not managing N loading into this
      system as N may significantly impact cyanobacterial bloom size and toxicity.

PMID- 25992593
TI  - GPCR-Based Chemical Biosensors for Medium-Chain Fatty Acids.
AB  - A key limitation to engineering microbes for chemical production is a reliance on
      low-throughput chromatography-based screens for chemical detection. While
      colorimetric chemicals are amenable to high-throughput screens, many value-added
      chemicals are not colorimetric and require sensors for high-throughput screening.
      Here, we use G-protein coupled receptors (GPCRs) known to bind medium-chain fatty
      acids in mammalian cells to rapidly construct chemical sensors in yeast. Medium
      chain fatty acids are immediate precursors to the advanced biofuel fatty acid
      methyl esters, which can serve as a "drop-in" replacement for D2 diesel. One of
      the sensors detects even-chain C8-C12 fatty acids with a 13- to 17-fold increase
      in signal after activation, with linear ranges up to 250 MUM. Introduction of a
      synthetic response unit alters both dynamic and linear range, improving the
      sensor response to decanoic acid to a 30-fold increase in signal after
      activation, with a linear range up to 500 MUM. To our knowledge, this is the
      first report of a whole-cell medium-chain fatty acid biosensor, which we envision
      could be applied to the evolutionary engineering of fatty acid-producing
      microbes. Given the affinity of GPCRs for a wide range of chemicals, it should be
      possible to rapidly assemble new biosensors by simply swapping the GPCR sensing
      unit. These sensors should be amenable to a variety of applications that require
      different dynamic and linear ranges, by introducing different response units. 

PMID- 25992595
TI  - Metal-Free Difunctionalization of Alkynes with 2-Chlorodithiane for Synthesis of
      beta-Ketodithianes.
AB  - Dithianes are versatile umpolung intermediates in organic synthesis but have
      rarely been employed in radical cross-coupling reactions. Here we describe the
      oxidative coupling method for alkyne difunctionalization under metal-catalyst
      free conditions. The efficient protocol directly affords a variety of beta
      ketodithianes in good to excellent yields with high regioselectivities. It
      provides a general pathway for accessing valuable dithianes with controlled
      formation of a new C-C bond and a C-O bond via a radical coupling pathway. 

PMID- 25992596
TI  - Why trans- or cis-Dimethyl Fumarate Addition to 2,5-Dimethylpyrrole Gives
      Exclusively trans-7-Azanorbornane.
AB  - The addition mechanism of dimethyl fumarate into 2,5-dimethylpyrrole is explored
      using density functional theory (DFT) methods. Our calculations find that
      TpW(NO)(PMe3)(eta(2)-3H-2,5-dimethylpyrrole) prefers to undergo two TpW(NO)(PMe3)
      migrations, two 1,5-hydride migrations, and one reductive elimination to
      isomerize into TpW(NO)(PMe3)(eta(2)-1H-2,5-dimethylpyrrole), in which
      TpW(NO)(PMe3) plays a proton-transfer role. trans-Dimethyl fumarate and
      TpW(NO)(PMe3)(eta(2)-1H-2,5-dimethylpyrrole) tend to adopt a concerted
      cycloaddition manner to afford trans-7-azanorbornane with a free-energy barrier
      of 21.8 kcal/mol. cis-Dimethyl fumarate and TpW(NO)(PMe3)(eta(2)-1H-2,5
      dimethylpyrrole) are the most likely to experience a concerted cycloaddition ->
      ring opening -> ring closing process to provide trans-7-azanorbornane in which
      the concerted cycloaddition and the ring-opening process are in dynamic
      equilibrium (with similar energy barriers of 21.5 and 21.9 kcal/mol,
      respectively). The presence of TpW(NO)(PMe3) not only promotes the cycloaddition
      of trans- or cis-dimethyl fumarate with 2,5-dimethylpyrrole by donating d
      electrons of the W atom into the diene system of the Diels-Alder reaction, but
      also is favorable for the ring-opening process of the formed cis-7-azanorbornane.
      Furthermore, trans-azanorbornane is 7.4 kcal/mol more stable than cis
      azanorbornane. Our calculations provide a new explanation of the addition of
      dimethyl fumarate with 2,5-dimethylpyrrole exclusively giving trans-7
      azanorbornane. 

PMID- 25992597
TI  - Intensity Enhanced Cerenkov Luminescence Imaging Using Terbium-Doped Gd2O2S
      Microparticles.
AB  - Weak intensity and poor penetration depth are two big obstacles toward clinical
      use of Cerenkov luminescence imaging (CLI). In this proof-of-concept study, we
      overcame these limitations by using lanthanides-based radioluminescent
      microparticles (RLMPs), called terbium doped Gd2O2S. The characterization
      experiment showed that the emission excited by Cerenkov luminescence can be
      neglected whereas the spectrum experiment demonstrated that the RLMPs can
      actually be excited by gamma-rays. A series of in vitro experiments demonstrated
      that RLMPs significantly improve the intensity and the penetration capacity of
      CLI, which has been extended to as deep as 15 mm. In vivo pseudotumor study
      further prove the huge potential of this enhancement strategy for Cerenkov
      luminescence imaging in living animal studies. 

PMID- 25992599
TI  - Ex vivo imaging of postnatal cerebellar granule cell migration using confocal
      macroscopy.
AB  - During postnatal development, immature granule cells (excitatory interneurons)
      exhibit tangential migration in the external granular layer, and then radial
      migration in the molecular layer and the Purkinje cell layer to reach the
      internal granular layer of the cerebellar cortex. Default in migratory processes
      induces either cell death or misplacement of the neurons, leading to deficits in
      diverse cerebellar functions. Centripetal granule cell migration involves several
      mechanisms, such as chemotaxis and extracellular matrix degradation, to guide the
      cells towards their final position, but the factors that regulate cell migration
      in each cortical layer are only partially known. In our method, acute cerebellar
      slices are prepared from P10 rats, granule cells are labeled with a fluorescent
      cytoplasmic marker and tissues are cultured on membrane inserts from 4 to 10 hr
      before starting real-time monitoring of cell migration by confocal macroscopy at
      37  degrees C in the presence of CO2. During their migration in the different
      cortical layers of the cerebellum, granule cells can be exposed to neuropeptide
      agonists or antagonists, protease inhibitors, blockers of intracellular effectors
      or even toxic substances such as alcohol or methylmercury to investigate their
      possible role in the regulation of neuronal migration. 

PMID- 25992594
TI  - Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes.

PMID- 25992598
TI  - A structure-based extracellular matrix expansion mechanism of fibrous tissue
      growth.
AB  - Embryonic growth occurs predominately by an increase in cell number; little is
      known about growth mechanisms later in development when fibrous tissues account
      for the bulk of adult vertebrate mass. We present a model for fibrous tissue
      growth based on 3D-electron microscopy of mouse tendon. We show that the number
      of collagen fibrils increases during embryonic development and then remains
      constant during postnatal growth. Embryonic growth was explained predominately by
      increases in fibril number and length. Postnatal growth arose predominately from
      increases in fibril length and diameter. A helical crimp structure was
      established in embryogenesis, and persisted postnatally. The data support a model
      where the shape and size of tendon is determined by the number and position of
      embryonic fibroblasts. The collagen fibrils that these cells synthesise provide a
      template for postnatal growth by structure-based matrix expansion. The model has
      important implications for growth of other fibrous tissues and fibrosis. 

PMID- 25992600
TI  - Applying the ARRIVE Guidelines to an In Vivo Database.
AB  - The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were
      developed to address the lack of reproducibility in biomedical animal studies and
      improve the communication of research findings. While intended to guide the
      preparation of peer-reviewed manuscripts, the principles of transparent reporting
      are also fundamental for in vivo databases. Here, we describe the benefits and
      challenges of applying the guidelines for the International Mouse Phenotyping
      Consortium (IMPC), whose goal is to produce and phenotype 20,000 knockout mouse
      strains in a reproducible manner across ten research centres. In addition to
      ensuring the transparency and reproducibility of the IMPC, the solutions to the
      challenges of applying the ARRIVE guidelines in the context of IMPC will provide
      a resource to help guide similar initiatives in the future. 

PMID- 25992602
TI  - A Questionnaire for the Assessment of Violent Behaviors in Young Couples: The
      Italian Version of Dating Violence Questionnaire (DVQ).
AB  - In the last years, intimate partner violence (IPV) became a relevant problem for
      community and for social life, particularly in young people. Its correct
      assessment and evaluation in the population is mandatory. Our objectives were:
      Confirm factor structure of Dating Violence Questionnaire (DVQ) and investigate
      its convergent and divergent validity. The DVQ along with other personality
      measures were filled by a sample of 418 university students (Females = 310) of
      average age of 23 y.o. (SD = 4.71). A subsample of participants (223 students)
      consented in being involved also in retest and filled also the Revised Eysenck
      Personality Questionnaire (short form) and a brief scale for describing the
      behavior of the (past) partner after the breaking of the relationship (BRS). The
      8-factor structure, with respect to the two other competing models, reported
      better fit indexes and showed significant correlations with other personality
      measures. Personality traits, both Neuroticism and Psychoticism, correlated with
      Sexual Violence, while Detachment correlated only with Neuroticism and Coercion,
      Humiliation and Physical Violence correlated with only Psychoticism. Extraversion
      did not report significant relationships with any of the 8 DVQ factors. Also the
      predictive validity of DVQ was satisfactory with the partner violent reaction to
      the break of relationship predicted positively predicted by Coercion (b = 0.22)
      and by Humiliation (b = 0.20) and negatively by Emotional Punishment (b = -0.18).
      The present results indicate a good factor structure of the questionnaire, and
      interesting correlations with personality traits, allowing to identify
      psychological aspects with a predisposing role for anti-social aggressive
      behaviors. Further studies will be aimed at ascertaining other possible
      determinants of intimate partner violence and the weight of cultural aspects. 

PMID- 25992601
TI  - Striatal-enriched protein tyrosine phosphatase controls responses to aversive
      stimuli: implication for ethanol drinking.
AB  - The STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific
      phosphatase whose dysregulation in expression and/or activity is associated with
      several neuropsychiatric disorders. We recently showed that long-term excessive
      consumption of ethanol induces a sustained inhibition of STEP activity in the
      dorsomedial striatum (DMS) of mice. We further showed that down-regulation of
      STEP expression in the DMS, and not in the adjacent dorsolateral striatum,
      increases ethanol intake, suggesting that the inactivation of STEP in the DMS
      contributes to the development of ethanol drinking behaviors. Here, we compared
      the consequence of global deletion of the STEP gene on voluntary ethanol intake
      to the consumption of an appetitive rewarding substance (saccharin) or an
      aversive solution (quinine or denatonium). Whereas saccharin intake was similar
      in STEP knockout (KO) and wild type (WT) littermate mice, the consumption of
      ethanol as well as quinine and denatonium was increased in STEP KO mice. These
      results suggested that the aversive taste of these substances was masked upon
      deletion of the STEP gene. We therefore hypothesized that STEP contributes to the
      physiological avoidance towards aversive stimuli. To further test this
      hypothesis, we measured the responses of STEP KO and WT mice to lithium-induced
      conditioned place aversion (CPA) and found that whereas WT mice developed lithium
      place aversion, STEP KO mice did not. In contrast, conditioned place preference
      (CPP) to ethanol was similar in both genotypes. Together, our results indicate
      that STEP contributes, at least in part, to the protection against the ingestion
      of aversive agents. 

PMID- 25992603
TI  - Perceived loudness of self-generated sounds is differentially modified by
      expected sound intensity.
AB  - Performing actions with sensory consequences modifies physiological and
      behavioral responses relative to otherwise identical sensory input perceived in a
      passive manner. It is assumed that such modifications occur through an efference
      copy sent from motor cortex to sensory regions during performance of voluntary
      actions. In the auditory domain most behavioral studies report attenuated
      perceived loudness of self-generated auditory action-consequences. However,
      several recent behavioral and physiological studies report enhanced responses to
      such consequences. Here we manipulated the intensity of self-generated and
      externally-generated sounds and examined the type of perceptual modification
      (enhancement vs. attenuation) reported by healthy human subjects. We found that
      when the intensity of self-generated sounds was low, perceived loudness is
      enhanced. Conversely, when the intensity of self-generated sounds was high,
      perceived loudness is attenuated. These results might reconcile some of the
      apparent discrepancies in the reported literature and suggest that efference
      copies can adapt perception according to the differential sensory context of
      voluntary actions. 

PMID- 25992605
TI  - Bioconversion of Gibberellin Fermentation Residue into Feed Supplement and
      Organic Fertilizer Employing Housefly (Musca domestica L.) Assisted by
      Corynebacterium variabile.
AB  - The accumulation of a considerable quantity of gibberellin fermentation residue
      (GFR) during gibberellic acid A3 (GA3) production not only results in the waste
      of many resources, but also poses a potential hazard to the environment,
      indicating that the safe treatment of GFR has become an urgent issue for GA3
      industry. The key to recycle GFR is converting it into an available resource and
      removing the GA3 residue. To this end, we established a co-bioconversion process
      in this study using house fly larvae (HFL) and microbes (Corynebacterium
      variabile) to convert GFR into insect biomass and organic fertilizer. About 85.5%
      GA3 in the GFR was removed under the following optimized solid-state fermentation
      conditions: 60% GFR, 40% rice straw powder, pH 8.5 and 6 days at 26  degrees C. A
      total of 371 g housefly larvae meal and 2,064 g digested residue were bio
      converted from 3,500 g raw GFR mixture contaning1, 400 g rice straw in the unit
      of (calculated) dry matter. HFL meal derived from GFR contained 56.4% protein,
      21.6% fat, and several essential amino acids, suggesting that it is a potential
      alternative animal feed protein source. Additionally, the digested GFR could be
      utilized as an organic fertilizer with a content of 3.2% total nitrogen, 2.0%
      inorganic phosphorus, 1.3% potassium and 91.5% organic matter. This novel GFR bio
      conversion method can mitigate potential environmental pollution and recycle the
      waste resources.

PMID- 25992604
TI  - Transcription of the Human Microsomal Epoxide Hydrolase Gene (EPHX1) Is Regulated
      by PARP-1 and Histone H1.2. Association with Sodium-Dependent Bile Acid
      Transport.
AB  - Microsomal epoxide hydrolase (mEH) is a bifunctional protein that plays a central
      role in the metabolism of numerous xenobiotics as well as mediating the sodium
      dependent transport of bile acids into hepatocytes. These compounds are involved
      in cholesterol homeostasis, lipid digestion, excretion of xenobiotics and the
      regulation of several nuclear receptors and signaling transduction pathways.
      Previous studies have demonstrated the critical role of GATA-4, a C/EBPalpha-NF/Y
      complex and an HNF-4alpha/CAR/RXR/PSF complex in the transcriptional regulation
      of the mEH gene (EPHX1). Studies also identified heterozygous mutations in human
      EPHX1 that resulted in a 95% decrease in mEH expression levels which was
      associated with a decrease in bile acid transport and severe hypercholanemia. In
      the present investigation we demonstrate that EPHX1 transcription is
      significantly inhibited by two heterozygous mutations observed in the Old Order
      Amish population that present numerous hypercholanemic subjects in the absence of
      liver damage suggesting a defect in bile acid transport into the hepatocyte. The
      identity of the regulatory proteins binding to these sites, established using
      biotinylated oligonucleotides in conjunction with mass spectrometry was shown to
      be poly(ADP-ribose)polymerase-1 (PARP-1) bound to the EPHX1 proximal promoter and
      a linker histone complex, H1.2/Aly, bound to a regulatory intron 1 site. These
      sites exhibited 71% homology and may represent potential nucleosome positioning
      domains. The high frequency of the H1.2 site polymorphism in the Amish population
      results in a potential genetic predisposition to hypercholanemia and in
      conjunction with our previous studies, further supports the critical role of mEH
      in mediating bile acid transport into hepatocytes. 

PMID- 25992606
TI  - Phylogenomic analysis reveals deep divergence and recombination in an
      economically important grapevine virus.
AB  - The evolutionary history of the exclusively grapevine (Vitis spp.) infecting,
      grapevine leafroll-associated virus 3 (GLRaV-3) has not been studied extensively,
      partly due to limited available sequence data. In this study we trace the
      evolutionary history of GLRaV-3, focussing on isolate GH24, a newly discovered
      variant. GH24 was discovered through the use of next-generation sequencing (NGS)
      and the whole genome sequence determined and validated with Sanger sequencing. We
      assembled an alignment of all 13 available whole genomes of GLRaV-3 isolates and
      all other publicly available GLRaV-3 sequence data. Using multiple recombination
      detection methods we identified a clear signal for recombination in one whole
      genome sequence and further evidence for recombination in two more, including
      GH24. We inferred phylogenetic trees and networks and estimated the ages of
      common ancestors of GLRaV-3 clades by means of relaxed clock models calibrated
      with asynchronous sampling dates. Our results generally confirm previously
      identified variant groups as well as two new groups (VII and VIII). Higher order
      groups were defined as supergroups designated A to D. Supergroup A includes
      variant groups I-V and supergroup B group VI and its related unclassified
      isolates. Supergroups C and D are less well known, including the newly identified
      groups VII (including isolate GH24) and VIII respectively. The inferred node ages
      suggest that the origins of the major groups of GLRaV-3, including isolate GH24,
      may have occurred prior to worldwide cultivation of grapevines, whilst the
      current diversity represents closely related isolates that diverged from common
      ancestors within the last century. 

PMID- 25992607
TI  - Robust Linear Models for Cis-eQTL Analysis.
AB  - Expression Quantitative Trait Loci (eQTL) analysis enables characterisation of
      functional genetic variation influencing expression levels of individual genes.
      In outbread populations, including humans, eQTLs are commonly analysed using the
      conventional linear model, adjusting for relevant covariates, assuming an allelic
      dosage model and a Gaussian error term. However, gene expression data generally
      have noise that induces heavy-tailed errors relative to the Gaussian distribution
      and often include atypical observations, or outliers. Such departures from
      modelling assumptions can lead to an increased rate of type II errors (false
      negatives), and to some extent also type I errors (false positives). Careful
      model checking can reduce the risk of type-I errors but often not type II errors,
      since it is generally too time-consuming to carefully check all models with a non
      significant effect in large-scale and genome-wide studies. Here we propose the
      application of a robust linear model for eQTL analysis to reduce adverse effects
      of deviations from the assumption of Gaussian residuals. We present results from
      a simulation study as well as results from the analysis of real eQTL data sets.
      Our findings suggest that in many situations robust models have the potential to
      provide more reliable eQTL results compared to conventional linear models,
      particularly in respect to reducing type II errors due to non-Gaussian noise.
      Post-genomic data, such as that generated in genome-wide eQTL studies, are often
      noisy and frequently contain atypical observations. Robust statistical models
      have the potential to provide more reliable results and increased statistical
      power under non-Gaussian conditions. The results presented here suggest that
      robust models should be considered routinely alongside other commonly used
      methodologies for eQTL analysis. 

PMID- 25992608
TI  - Enhanced mitochondrial superoxide scavenging does not improve muscle insulin
      action in the high fat-fed mouse.
AB  - Improving mitochondrial oxidant scavenging may be a viable strategy for the
      treatment of insulin resistance and diabetes. Mice overexpressing the
      mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or
      transgenically expressing catalase within the mitochondrial matrix (mcat(tg)
      mice) have increased scavenging of O2(-) and H2O2, respectively. Furthermore,
      muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice.
      The goal of the current study was to test the hypothesis that increased O2(-)
      scavenging alone or in combination with increased H2O2 scavenging (mtAO mice)
      enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was
      examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg),
      mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps)
      combined with radioactive glucose tracers following sixteen weeks of normal chow
      or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose
      disappearance, and muscle glucose uptake during the insulin clamp were similar in
      chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed
      mcat(tg) mice had improved muscle insulin action, however, an additive effect was
      not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from
      clamped mice was consistent with glucose flux measurements. These results
      demonstrate that increased O2(-) scavenging does not improve muscle insulin
      action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging.

PMID- 25992609
TI  - The long term response of birds to climate change: new results from a cold stage
      avifauna in northern England.
AB  - The early MIS 3 (55-40 Kyr BP associated with Middle Palaeolithic archaeology)
      bird remains from Pin Hole, Creswell Crags, Derbyshire, England are analysed in
      the context of the new dating of the site's stratigraphy. The analysis is
      restricted to the material from the early MIS 3 level of the cave because the
      upper fauna is now known to include Holocene material as well as that from the
      Late Glacial. The results of the analysis confirm the presence of the taxa,
      possibly unexpected for a Late Pleistocene glacial deposit including records such
      as Alpine swift, demoiselle crane and long-legged buzzard with southern and/or
      eastern distributions today. These taxa are accompanied by more expected ones
      such as willow ptarmigan /red grouse and rock ptarmigan living today in northern
      and montane areas. Finally, there are temperate taxa normally requiring trees for
      nesting such as wood pigeon and grey heron. Therefore, the result of the analysis
      is that the avifauna of early MIS 3 in England included taxa whose ranges today
      do not overlap making it a non-analogue community similar to the many steppe
      tundra mammalian faunas of the time. The inclusion of more temperate and woodland
      taxa is discussed in the light that parts of northern Europe may have acted as
      cryptic northern refugia for some such taxa during the last glacial. These
      records showing former ranges of taxa are considered in the light of modern
      phylogeographic studies as these often assume former ranges without considering
      the fossil record of those taxa. In addition to the anomalous combination of taxa
      during MIS 3 living in Derbyshire, the individuals of a number of the taxa are
      different in size and shape to members of the species today probably due to the
      high carrying capacity of the steppe-tundra. 

PMID- 25992610
TI  - Correction: Co-Infection with Mycobacterium tuberculosis Impairs HIV-Specific
      CD8+ and CD4+ T Cell Functionality.

PMID- 25992612
TI  - Correction: Tissue elasticity regulated tumor gene expression: implication for
      diagnostic biomarkers of primitive neuroectodermal tumor.

PMID- 25992611
TI  - Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease
      Progression in Breast Cancer Patients.
AB  - Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid
      cells, which increase in cancer patients. The molecular mechanism behind their
      generation and function is unclear. Whereas granulocytic-MDSCs correlate with
      poor overall survival in breast cancer, the presence and relevance of monocytic
      MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of
      functional blood Mo-MDSCs in breast cancer patients before they acquire a typical
      Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell
      surface phenotype (CD14(+)HLA-DR(low/-)CD86(low/-)CD80(low/-)CD163(low/-))
      increased significantly first during disease progression and correlated to
      metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising
      the Mo-MDSC population, from patients with metastatic breast cancer resemble the
      reprogrammed immunosuppressive monocytes in patients with severe infections, both
      by their surface and functional phenotype but also at their molecular gene
      expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast
      cancer patients may represent a novel and simple biomarker for assessing disease
      progression.

PMID- 25992613
TI  - MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets
      Multiple Oncogenes.
AB  - miRNAs play a central role in numerous pathologies including multiple cancer
      types. miR-191 has predominantly been studied as an oncogene, but the role of miR
      191 in the proliferation of primary cells is not well characterized, and the miR
      191 targetome has not been experimentally profiled. Here we utilized RNA induced
      silencing complex immunoprecipitations as well as gene expression profiling to
      construct a genome wide miR-191 target profile. We show that miR-191 represses
      proliferation in primary human fibroblasts, identify multiple proto-oncogenes as
      novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence
      that miR-191 extensively mediates target expression through coding sequence (CDS)
      pairing. Our results provide a comprehensive genome wide miR-191 target profile,
      and demonstrate miR-191's regulation of primary human fibroblast proliferation. 

PMID- 25992614
TI  - Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor,
      sulfonylurea, and pioglitazone therapy, all in combination with metformin, for
      type 2 diabetes: a population-based cohort study.
AB  - BACKGROUND/OBJECTIVES: Data on the comparative effectiveness of oral
      antidiabetics on cardiovascular outcomes in a clinical practice setting are
      limited. This study sought to determine whether a differential risk of
      cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase
      4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus
      metformin or pioglitazone plus metformin. METHODS: We conducted a cohort study of
      349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or
      pioglitazone plus metformin for type 2 diabetes using the Korean national health
      insurance claims database. The incidence of total CVD and individual outcomes of
      myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were
      assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards
      model weighted for a propensity score. RESULTS: During follow-up, 3,881 patients
      developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with
      95% confidence interval (CI) for a sulfonylurea derivative plus metformin
      compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total
      CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for
      IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus
      metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81
      (0.67-0.99), respectively. CONCLUSIONS: Compared with a DPP-4 inhibitor plus
      metformin, treatment with a sulfonylurea drug plus metformin was associated with
      increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus
      metformin was associated with decreased total CVD and IS risks.

PMID- 25992615
TI  - TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and
      Resorption.
AB  - Plekhm1 is a large, multi-modular, adapter protein implicated in osteoclast
      vesicle trafficking and bone resorption. In patients, inactivating mutations
      cause osteopetrosis, and gain-of-function mutations cause osteopenia.
      Investigations of potential Plekhm1 interaction partners by mass spectrometry
      identified TRAFD1 (FLN29), a protein previously shown to suppress toll-like
      receptor signaling in monocytes/macrophages, thereby dampening inflammatory
      responses to innate immunity. We mapped the binding domains to the TRAFD1 zinc
      finger (aa 37-60), and to the region of Plekhm1 between its second pleckstrin
      homology domain and its C1 domain (aa 784-986). RANKL slightly increased TRAFD1
      levels, particularly in primary osteoclasts, and the co-localization of TRAFD1
      with Plekhm1 also increased with RANKL treatment. Stable knockdown of TRAFD1 in
      RAW 264.7 cells inhibited resorption activity proportionally to the degree of
      knockdown, and inhibited acidification. The lack of acidification occurred
      despite the presence of osteoclast acidification factors including carbonic
      anhydrase II, a3-V-ATPase, and the ClC7 chloride channel. Secretion of TRAP and
      cathepsin K were also markedly inhibited in knockdown cells. Truncated Plekhm1 in
      ia/ia osteopetrotic rat cells prevented vesicle localization of Plekhm1 and
      TRAFD1. We conclude that TRAFD1, in association with Plekhm1/Rab7-positive late
      endosomes-early lysosomes, has a previously unknown role in vesicle trafficking,
      acidification, and resorption in osteoclasts. 

PMID- 25992616
TI  - The effects of temperature on political violence: global evidence at the
      subnational level.
AB  - A number of studies have demonstrated an empirical relationship between higher
      ambient temperatures and substate violence, which have been extrapolated to make
      predictions about the security implications of climate change. This literature
      rests on the untested assumption that the mechanism behind the temperature
      conflict link is that disruption of agricultural production provokes local
      violence. Using a subnational-level dataset, this paper demonstrates that the
      relationship: (1) obtains globally, (2) exists at the substate level--provinces
      that experience positive temperature deviations see increased conflict; and (3)
      occurs even in regions without significant agricultural production. Diminished
      local farm output resulting from elevated temperatures is unlikely to account for
      the entire increase in substate violence. The findings encourage future research
      to identify additional mechanisms, including the possibility that a substantial
      portion of the variation is brought about by the well-documented direct effects
      of temperature on individuals' propensity for violence or through macroeconomic
      mechanisms such as food price shocks.

PMID- 25992617
TI  - Asian elephants in China: estimating population size and evaluating habitat
      suitability.
AB  - We monitored the last remaining Asian elephant populations in China over the past
      decade. Using DNA tools and repeat genotyping, we estimated the population sizes
      from 654 dung samples collected from various areas. Combined with morphological
      individual identifications from over 6,300 elephant photographs taken in the
      wild, we estimated that the total Asian elephant population size in China is
      between 221 and 245. Population genetic structure and diversity were examined
      using a 556-bp fragment of mitochondrial DNA, and 24 unique haplotypes were
      detected from DNA analysis of 178 individuals. A phylogenetic analysis revealed
      two highly divergent clades of Asian elephants, alpha and beta, present in
      Chinese populations. Four populations (Mengla, Shangyong, Mengyang, and Pu'Er)
      carried mtDNA from the alpha clade, and only one population (Nangunhe) carried
      mtDNA belonging to the beta clade. Moreover, high genetic divergence was observed
      between the Nangunhe population and the other four populations; however, genetic
      diversity among the five populations was low, possibly due to limited gene flow
      because of habitat fragmentation. The expansion of rubber plantations, crop
      cultivation, and villages along rivers and roads had caused extensive degradation
      of natural forest in these areas. This had resulted in the loss and fragmentation
      of elephant habitats and had formed artificial barriers that inhibited elephant
      migration. Using Geographic Information System, Global Positioning System, and
      Remote Sensing technology, we found that the area occupied by rubber plantations,
      tea farms, and urban settlements had dramatically increased over the past 40
      years, resulting in the loss and fragmentation of elephant habitats and forming
      artificial barriers that inhibit elephant migration. The restoration of
      ecological corridors to facilitate gene exchange among isolated elephant
      populations and the establishment of cross-boundary protected areas between China
      and Laos to secure their natural habitats are critical for the survival of Asian
      elephants in this region. 

PMID- 25992618
TI  - Trial-results reporting and academic medical centers.

PMID- 25992619
TI  - Molecular Epidemiology and Phylogenetic Analysis of Human Adenovirus Caused an
      Outbreak in Taiwan during 2011.
AB  - An outbreak of adenovirus has been surveyed in Taiwan in 2011. To better
      understand the evolution and epidemiology of adenovirus in Taiwan, full-length
      sequence of hexon and fiber coapsid protein was analyzed using series of
      phylogenetic and dynamic evolution tools. Six different serotypes were identified
      in this outbreak and the species B was predominant (HAdV-3, 71.50%; HAdV-7,
      15.46%). The most frequent diagnosis was acute tonsillitis (54.59%) and
      bronchitis (47.83%). Phylogenetic analysis revealed that hexon protein gene
      sequences were highly conserved for HAdV-3 and HAdV-7 circulation in Taiwan.
      However, comparison of restriction fragment length polymorphism (RFLP) analysis
      and phylogenetic trees of fiber gene in HAdV-7 clearly indicated that the
      predominant genotype in Taiwan has shifted from 7b to 7d. Several positive
      selection sites were observed in hexon protein. The estimated nucleotide
      substitution rates of hexon protein of HAdV-3 and HAdV-7 were 0.234*10-3
      substitutions/site/year (95% HPD: 0.387~0.095*10-3) and 1.107*10-3 (95% HPD: 0.
      541~1.604) respectively; those of the fiber protein of HAdV-3 and HAdV-7 were
      1.085*10-3 (95% HPD: 1.767~0.486) and 0.132*10-3 (95% HPD: 0.283~0.014)
      respectively. Phylodynamic analysis by Bayesian skyline plot (BSP) suggested that
      using individual gene to evaluate the effective population size might possibly
      cause miscalculation. In summary, the virus evolution is ongoing, and continuous
      surveillance of this virus evolution will contribute to the control of the
      epidemic. 

PMID- 25992620
TI  - Quality of inpatient pediatric case management for four leading causes of child
      mortality at six government-run Ugandan hospitals.
AB  - BACKGROUND: A better understanding of case management practices is required to
      improve inpatient pediatric care in resource-limited settings. Here we utilize
      data from a unique health facility-based surveillance system at six Ugandan
      hospitals to evaluate the quality of pediatric case management and the factors
      associated with appropriate care. METHODS: All children up to the age of 14 years
      admitted to six district or regional hospitals over 15 months were included in
      the study. Four case management categories were defined for analysis: suspected
      malaria, selected illnesses requiring antibiotics, suspected anemia, and
      diarrhea. The quality of case management for each category was determined by
      comparing recorded treatments with evidence-based best practices as defined in
      national guidelines. Associations between variables of interest and the receipt
      of appropriate case management were estimated using multivariable logistic
      regression. RESULTS: A total of 30,351 admissions were screened for inclusion in
      the analysis. Ninety-two percent of children met criteria for suspected malaria
      and 81% received appropriate case management. Thirty-two percent of children had
      selected illnesses requiring antibiotics and 89% received appropriate
      antibiotics. Thirty percent of children met criteria for suspected anemia and 38%
      received appropriate case management. Twelve percent of children had diarrhea and
      18% received appropriate case management. Multivariable logistic regression
      revealed large differences in the quality of care between health facilities.
      There was also a strong association between a positive malaria diagnostic test
      result and the odds of receiving appropriate case management for comorbid non
      malarial illnesses - children with a positive malaria test were more likely to
      receive appropriate care for anemia and less likely for illnesses requiring
      antibiotics and diarrhea. CONCLUSIONS: Appropriate management of suspected anemia
      and diarrhea occurred infrequently. Pediatric quality improvement initiatives
      should target deficiencies in care unique to each health facility, and
      interventions should focus on the simultaneous management of multiple diagnoses.

PMID- 25992622
TI  - Normobaric hyperoxia for treatment of pneumocephalus after posterior fossa
      surgery in the semisitting position: a prospective randomized controlled trial.
AB  - BACKGROUND: Supratentorial pneumocephalus after posterior fossa surgery in the
      semisitting position may lead to decreased alertness and other symptoms. We here
      aimed to prove the efficacy of normobaric hyperoxia on the absorption of
      postoperative pneumocephalus according to a standardized treatment protocol.
      METHODS AND FINDINGS: We enrolled 44 patients with postoperative supratentorial
      pneumocephalus (> 30 ml) after posterior fossa surgery in a semisitting position.
      After randomisation procedure, patients received either normobaric hyperoxia at
      FiO2 100% over an endotracheal tube for 3 hours (treatment arm) or room air
      (control arm). Routine cranial CT scans were performed immediately (CT1) and 24
      hours (CT2) after completion of surgery and were rated without knowledge of the
      therapy arm. Two co-primary endpoints were assessed: (i) mean change of
      pneumocephalus volume, and (ii) air resorption rate in 24 hours. Secondary
      endpoints were subjective alertness (Stanford Sleepiness Scale) postoperatively
      and attention (Stroop test), which were evaluated preoperatively and 24 hours
      after surgery. The mean change in pneumocephalus volume was higher in patients in
      the treatment arm as compared to patients in the control arm (p = 0.001). The air
      resorption rate was higher in patients in the treatment arm as compared to
      patients in the control arm (p = 0.0015). Differences were more pronounced in
      patients aged 52 years and older. No difference between patients in treatment arm
      and control arm was observed for the Stroop test. The distribution of scores in
      the Stanford Sleepiness Scale differed in the treatment arm as compared to the
      control arm, and there was a difference in mean values (p = 0.015). CONCLUSIONS:
      Administration of normobaric hyperoxia at FiO2 100% via an endotracheal tube for
      3 hours is safe and efficacious in the treatment of pneumocephalus after
      posterior fossa surgery in the semisitting position. Largest benefit was found in
      elderly patients and particularly in older men. TRIAL REGISTRATION: German
      Clinical Trials Register DRKS00006273.

PMID- 25992621
TI  - Epidemiology of pediatric functional abdominal pain disorders: a meta-analysis.
AB  - OBJECTIVE: We aimed to review the literature regarding epidemiology of functional
      abdominal pain disorders in children and to assess its geographic, gender and age
      distribution including associated risk factors of developing functional abdominal
      pain. METHODS: The Cochrane Library, MEDLINE, EMBASE, CINAHL and PsychInfo
      databases were systematically searched up to February 2014. Study selection
      criteria included: (1) studies of birth cohort, school based or general
      population samples (2) containing data concerning epidemiology, prevalence or
      incidence (3) of children aged 4-18 years (4) suffering from functional abdominal
      pain. Quality of studies was rated by a self-made assessment tool. A random
      effect meta-analysis model was used to estimate the prevalence of functional
      abdominal pain in childhood. RESULTS: A total of 58 articles, including 196,472
      children were included. Worldwide pooled prevalence for functional abdominal pain
      disorders was 13.5% (95% CI 11.8-15.3), of which irritable bowel syndrome was
      reported most frequently (8.8%, 95% CI 6.2-11.9). The prevalence across studies
      ranged widely from 1.6% to 41.2%. Higher pooled prevalence rates were reported in
      South America (16.8%) and Asia (16.5%) compared to Europe (10.5%). And a higher
      pooled prevalence was reported when using the Rome III criteria (16.4%, 95% CI
      13.5-19.4). Functional abdominal pain disorders are shown to occur significantly
      more in girls (15.9% vs. 11.5%, pooled OR 1.5) and is associated with the
      presence of anxiety and depressive disorders, stress and traumatic life events.
      CONCLUSION: Functional abdominal pain disorders are a common problem worldwide
      with irritable bowel syndrome as most encountered abdominal pain-related
      functional gastrointestinal disorder. Female gender, psychological disorders,
      stress and traumatic life events affect prevalence.

PMID- 25992623
TI  - Fas Signaling Promotes Gastric Cancer Metastasis through STAT3-Dependent
      Upregulation of Fascin.
AB  - BACKGROUND: Fas signaling-activated signal transducers and activators of
      transcription 3 (STAT3) is required for Fascin upregulation. As an actin-bundling
      protein, Fascin can mediate gastric cancer (GC) cell migration. METHODS: Gastric
      cancer AGS cells were treated with anti-Fas (5 MUg/ml) for 2 h, in order to
      stimulate the activation of the Fas signaling. The in vitro migration of Fas
      signaling-activated AGS cells was assessed using Transwell chambers. The levels
      of Fascin and phosphorylated STAT3 were detected by Western blotting analyses.
      Nude mice were injected intravenously with AGS cells treated with anti-Fas or
      treated with STAT3 inhibitor without anti-Fas; tumor pulmonary metastases were
      measured. Fascin protein expression in tumor tissues was detected by
      immunohistochemistry. The Fas and Fascin mRNA levels in tumor tissues from
      patients with GC were measured by real-time PCR and their correlation was
      analyzed. RESULTS: The activation of Fas signaling promoted cell migration and
      resulted in STAT3-dependent Fascin upregulation in AGS cells. STAT3 enhanced
      Fascin levels in vivo. Fascin was the mediator of Fas signaling-induced AGS cell
      migration in vitro and in vivo. Furthermore, there was a positive correlation
      between Fas and Fascin mRNA levels in tumor tissues from GC patients.
      CONCLUSIONS: Fas signaling promotes GC metastasis through the STAT3/Fascin
      pathway, which may provide a new target for GC therapy.

PMID- 25992624
TI  - Hitting an Unintended Target: Phylogeography of Bombus brasiliensis Lepeletier,
      1836 and the First New Brazilian Bumblebee Species in a Century (Hymenoptera:
      Apidae).
AB  - This work tested whether or not populations of Bombus brasiliensis isolated on
      mountain tops of southeastern Brazil belonged to the same species as populations
      widespread in lowland areas in the Atlantic coast and westward along the Parana
      river valley. Phylogeographic and population genetic analyses showed that those
      populations were all conspecific. However, they revealed a previously
      unrecognized, apparently rare, and potentially endangered species in one of the
      most threatened biodiversity hotspots of the World, the Brazilian Atlantic
      Forest. This species is described here as Bombus bahiensis sp. n., and included
      in a revised key for the identification of the bumblebee species known to occur
      in Brazil. Phylogenetic analyses based on two mtDNA markers suggest this new
      species to be sister to B. brasiliensis, from which its workers and queens can be
      easily distinguished by the lack of a yellow hair-band on the first metasomal
      tergum. The results presented here are consistent with the hypothesis that B.
      bahiensis sp. n. may have originated from an ancestral population isolated in an
      evergreen-forest refuge (the so-called Bahia refuge) during cold, dry periods of
      the Pleistocene. This refuge is also known as an important area of endemism for
      several animal taxa, including other bees. Secondary contact between B. bahiensis
      and B. brasiliensis may be presently prevented by a strip of semi-deciduous
      forest in a climate zone characterized by relatively long dry seasons.
      Considering the relatively limited range of this new species and the current
      anthropic pressure on its environment, attention should be given to its
      conservation status. 

PMID- 25992625
TI  - Pyrosequencing characterization of the microbiota from Atlantic intertidal marine
      sponges reveals high microbial diversity and the lack of co-occurrence patterns.
AB  - Sponges are ancient metazoans that host diverse and complex microbial
      communities. Sponge-associated microbial diversity has been studied from wide
      oceans across the globe, particularly in subtidal regions, but the microbial
      communities from intertidal sponges have remained mostly unexplored. Here we used
      pyrosequencing to characterize the microbial communities in 12 different co
      occurring intertidal marine sponge species sampled from the Atlantic coast,
      revealing a total of 686 operational taxonomic units (OTUs) at 97% sequence
      similarity. Taxonomic assignment of 16S ribosomal RNA tag sequences estimated
      altogether 26 microbial groups, represented by bacterial (75.5%) and archaeal
      (22%) domains. Proteobacteria (43.4%) and Crenarchaeota (20.6%) were the most
      dominant microbial groups detected in all the 12 marine sponge species and
      ambient seawater. The Crenarchaeota microbes detected in three Atlantic Ocean
      sponges had a close similarity with Crenarchaeota from geographically separated
      subtidal Red Sea sponges. Our study showed that most of the microbial communities
      observed in sponges (73%) were also found in the surrounding ambient seawater
      suggesting possible environmental acquisition and/or horizontal transfer of
      microbes. Beyond the microbial diversity and community structure assessments
      (NMDS, ADONIS, ANOSIM), we explored the interactions between the microbial
      communities coexisting in sponges using the checkerboard score (C-score).
      Analyses of the microbial association pattern (co-occurrence) among intertidal
      sympatric sponges revealed the random association of microbes, favoring the
      hypothesis that the sponge-inhabiting microbes are recruited from the habitat
      mostly by chance or influenced by environmental factors to benefit the hosts. 

PMID- 25992626
TI  - Effects of visual feedback-induced variability on motor learning of handrim
      wheelchair propulsion.
AB  - BACKGROUND: It has been suggested that a higher intra-individual variability
      benefits the motor learning of wheelchair propulsion. The present study evaluated
      whether feedback-induced variability on wheelchair propulsion technique variables
      would also enhance the motor learning process. Learning was operationalized as an
      improvement in mechanical efficiency and propulsion technique, which are thought
      to be closely related during the learning process. METHODS: 17 Participants
      received visual feedback-based practice (feedback group) and 15 participants
      received regular practice (natural learning group). Both groups received equal
      practice dose of 80 min, over 3 weeks, at 0.24 W/kg at a treadmill speed of 1.11
      m/s. To compare both groups the pre- and post-test were performed without
      feedback. The feedback group received real-time visual feedback on seven
      propulsion variables with instruction to manipulate the presented variable to
      achieve the highest possible variability (1st 4-min block) and optimize it in the
      prescribed direction (2nd 4-min block). To increase motor exploration the
      participants were unaware of the exact variable they received feedback on. Energy
      consumption and the propulsion technique variables with their respective
      coefficient of variation were calculated to evaluate the amount of intra
      individual variability. RESULTS: The feedback group, which practiced with higher
      intra-individual variability, improved the propulsion technique between pre- and
      post-test to the same extent as the natural learning group. Mechanical efficiency
      improved between pre- and post-test in the natural learning group but remained
      unchanged in the feedback group. CONCLUSION: These results suggest that feedback
      induced variability inhibited the improvement in mechanical efficiency. Moreover,
      since both groups improved propulsion technique but only the natural learning
      group improved mechanical efficiency, it can be concluded that the improvement in
      mechanical efficiency and propulsion technique do not always appear
      simultaneously during the motor learning process. Their relationship is most
      likely modified by other factors such as the amount of the intra-individual
      variability.

PMID- 25992627
TI  - Investment in constitutive immune function by North American elk experimentally
      maintained at two different population densities.
AB  - Natural selection favors individuals that respond with effective and appropriate
      immune responses to macro or microparasites. Animals living in populations close
      to ecological carrying capacity experience increased intraspecific competition,
      and as a result are often in poor nutritional condition. Nutritional condition,
      in turn, affects the amount of endogenous resources that are available for
      investment in immune function. Our objective was to understand the relationship
      between immune function and density dependence mediated by trade-offs between
      immune function, nutritional condition, and reproduction. To determine how immune
      function relates to density-dependent processes, we quantified bacteria killing
      ability, hemolytic-complement activity, and nutritional condition of North
      American elk (Cervus elaphus) from populations maintained at experimentally high-
      and low-population densities. When compared with elk from the low-density
      population, those from the high-density population had higher bacteria killing
      ability and hemolytic-complement activity despite their lower nutritional
      condition. Similarly, when compared with adults, yearlings had higher bacteria
      killing ability, higher hemolytic-complement activity, and lower nutritional
      condition. Pregnancy status and lactational status did not change either measure
      of constitutive immunity. Density-dependent processes affected both nutritional
      condition and investment in constitutive immune function. Although the mechanism
      for how density affects immunity is ambiguous, we hypothesize two possibilities:
      (i) individuals in higher population densities and in poorer nutritional
      condition invested more into constitutive immune defenses, or (ii) had higher
      parasite loads causing higher induced immune responses. Those explanations are
      not mutually exclusive, and might be synergistic, but overall our results provide
      stronger support for the hypothesis that animals in poorer nutritional condition
      invest more in constitutive immune defenses then animals in better nutritional
      condition. This intriguing hypothesis should be investigated further within the
      larger framework of the cost and benefit structure of immune responses. 

PMID- 25992629
TI  - Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with
      Chronic Kidney Disease under Nephrology Care.
AB  - Primary kidney disease is suggested to affect renal prognosis of CKD patients;
      however, whether nephrology care modifies this association is unknown. We studied
      patients with CKD stage I-IV treated in a renal clinic and with established
      diagnosis of CKD cause to evaluate whether the risk of renal event (composite of
      end-stage renal disease and eGFR decline >= 40%) linked to the specific diagnosis
      is modified by the achievement or maintenance in the first year of nephrology
      care of therapeutic goals for hypertension (BP <= 130/80 mmHg in patients with
      proteinuria >= 1 50 mg/24h and/or diabetes and <= 140/90 in those with
      proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb >= 11 g/dL),
      and proteinuria (<= 0.5 g/24h). Survival analysis started after first year of
      nephrology care. We studied 729 patients (age 64 +/- 15 y; males 59.1%; diabetes
      34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%;
      glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial
      nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of
      Nephrology care, therapy was overall intensified in most patients and prevalence
      of main therapeutic goals generally improved. During subsequent follow up (median
      3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a
      higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28-10.6) and
      DN (1.28,2.99-3.05), versus HTN (reference), independently of age, gender, CVD,
      BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in
      the first year of nephrology care of each of the three main therapeutic goals. No
      interaction was found on the risk of CKD progression between diagnostic
      categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb
      (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology
      care, diagnosis of kidney disease should be considered in conjunction with the
      main risk factors to refine renal risk stratification.

PMID- 25992628
TI  - Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes
      Self-renewal and Tumor Progression of Glioma Stem Cells.
AB  - Epidermal growth factor receptor variant III (EGFRvIII) has been associated with
      glioma stemness, but the direct molecular mechanism linking the two is largely
      unknown. Here, we show that EGFRvIII induces the expression and secretion of
      pigment epithelium-derived factor (PEDF) via activation of signal transducer and
      activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor
      progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self
      renewal by Notch1 cleavage, and the generated intracellular domain of Notch1
      (NICD) induced the expression of Sox2 through interaction with its promoter
      region. Furthermore, a subpopulation with high levels of PEDF was capable of
      infiltration along corpus callosum. Inhibition of PEDF diminished GSC self
      renewal and increased survival of orthotopic tumor-bearing mice. Together, these
      data indicate the novel role of PEDF as a key regulator of GSC and suggest
      clinical implications. 

PMID- 25992631
TI  - Lower within-community variance of negative density dependence increases forest
      diversity.
AB  - Local abundance of adult trees impedes growth of conspecific seedlings through
      host-specific enemies, a mechanism first proposed by Janzen and Connell to
      explain plant diversity in forests. While several studies suggest the importance
      of this mechanism, there is still little information of how the variance of
      negative density dependence (NDD) affects diversity of forest communities. With
      computer simulations, we analyzed the impact of strength and variance of NDD
      within tree communities on species diversity. We show that stronger NDD leads to
      higher species diversity. Furthermore, lower range of strengths of NDD within a
      community increases species richness and decreases variance of species
      abundances. Our results show that, beyond the average strength of NDD, the
      variance of NDD is also crucially important to explain species diversity. This
      can explain the dissimilarity of biodiversity between tropical and temperate
      forest: highly diverse forests could have lower NDD variance. This report
      suggests that natural enemies and the variety of the magnitude of their effects
      can contribute to the maintenance of biodiversity. 

PMID- 25992630
TI  - Synergistic antifungal activity of berberine derivative B-7b and fluconazole.
AB  - Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used
      concomitantly exhibited a synergism against FLC-resistant Candida albicans in
      vitro. We also suggested BBR played a major antifungal role in the synergism of
      FLC and BBR, while FLC increased intracellular BBR concentrations. Our following
      systematic structural modification and reconstruction of BBR core identified the
      novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted
      phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable
      synergistic antifungal activity and low cytotoxicity. Here, the study mainly
      investigated the synergistic activity of FLC and B-7b and the underlying
      mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC
      resistant clinical isolates of C. albicans and non-C. albicans species, including
      Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and
      Cryptococcus neoformans. The potent synergistic activity of B-7b in combination
      with FLC against FLC-resistant C. albicans was found through the checkerboard
      microdilution assay. The findings of agar diffusion tests and time-kill curves
      confirmed its better synergism with FLC. And as expected, B-7b exhibited much
      lower cytotoxicity than BBR to human umbilical vein endothelial cells. In
      contrast to BBR, we found that endogenous ROS augmentation was not involved in
      the synergism of FLC and B-7b. According to the results from our present
      comparative proteomic study, it seemed that the disruption of protein folding and
      processing and the weakening of cells' self-defensive ability contributed to the
      synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR
      derivative B-7b could be a promising synergist in combination with FLC for the
      treatment of invasive fungal infections. 

PMID- 25992632
TI  - Promoting Balance in the Lives of Resident Physicians: A Call to Action.

PMID- 25992633
TI  - Step by step: microsurgical training method combining two nonliving animal
      models.
AB  - The learning of microsurgical techniques and the maintenance of microsurgical
      skills have been traditionally based on the use of living animals, mainly
      laboratory rats. This method although extremely valuable can be economically
      demanding both for the surgeon and the sponsoring institution; it also requires
      special training facilities that may not always be available or accessible.
      Furthermore ethical concerns can limit the use of living animals for training
      purposes. Alternative training methods, such as inert tubes and gloves have not
      gained popularity among surgeons since they do not offer an experience similar to
      that of a clinical situation. Non-living animal models include the use of chicken
      thighs and wings; they offer a practice experience that resembles a clinical
      situation to a considerable extent. This type of training is relatively cheap and
      easily available. The microscope and instruments required can be acquired over
      the internet, and the chicken pieces can be bought at the local supermarket. This
      approach allows a motivated trainee to rehearse different types of surgical
      techniques several times at a reasonable expense, helping to develop or maintain
      his surgical expertise if more complex facilities are not available. On the
      current manuscript we describe how to setup a small practice station, how to
      dissect the specimens, and how to practice both with the chicken thighs and with
      the chicken wings in a progressive fashion. This approach takes advantage on the
      versatility of the chicken thigh model and the small size of the chicken wing
      Brachial artery. 

PMID- 25992634
TI  - CTXphi Replication Depends on the Histone-Like HU Protein and the UvrD Helicase.
AB  - The Vibrio cholerae bacterium is the agent of cholera. The capacity to produce
      the cholera toxin, which is responsible for the deadly diarrhea associated with
      cholera epidemics, is encoded in the genome of a filamentous phage, CTXphi.
      Rolling-circle replication (RCR) is central to the life cycle of CTXphi because
      amplification of the phage genome permits its efficient integration into the
      genome and its packaging into new viral particles. A single phage-encoded HUH
      endonuclease initiates RCR of the proto-typical filamentous phages of
      enterobacteriaceae by introducing a nick at a specific position of the double
      stranded DNA form of the phage genome. The rest of the process is driven by host
      factors that are either essential or crucial for the replication of the host
      genome, such as the Rep SF1 helicase. In contrast, we show here that the histone
      like HU protein of V. cholerae is necessary for the introduction of a nick by the
      HUH endonuclease of CTXphi. We further show that CTXphi RCR depends on a SF1
      helicase normally implicated in DNA repair, UvrD, rather than Rep. In addition to
      CTXphi, we show that VGJphi, a representative member of a second family of vibrio
      integrative filamentous phages, requires UvrD and HU for RCR while TLCphi, a
      satellite phage, depends on Rep and is independent from HU. 

PMID- 25992635
TI  - Differential nuclear and mitochondrial DNA preservation in post-mortem teeth with
      implications for forensic and ancient DNA studies.
AB  - Major advances in genetic analysis of skeletal remains have been made over the
      last decade, primarily due to improvements in post-DNA-extraction techniques.
      Despite this, a key challenge for DNA analysis of skeletal remains is the limited
      yield of DNA recovered from these poorly preserved samples. Enhanced DNA recovery
      by improved sampling and extraction techniques would allow further advancements.
      However, little is known about the post-mortem kinetics of DNA degradation and
      whether the rate of degradation varies between nuclear and mitochondrial DNA or
      across different skeletal tissues. This knowledge, along with information
      regarding ante-mortem DNA distribution within skeletal elements, would inform
      sampling protocols facilitating development of improved extraction processes.
      Here we present a combined genetic and histological examination of DNA content
      and rates of DNA degradation in the different tooth tissues of 150 human molars
      over short-medium post-mortem intervals. DNA was extracted from coronal dentine,
      root dentine, cementum and pulp of 114 teeth via a silica column method and the
      remaining 36 teeth were examined histologically. Real time quantification assays
      based on two nuclear DNA fragments (67 bp and 156 bp) and one mitochondrial DNA
      fragment (77 bp) showed nuclear and mitochondrial DNA degraded exponentially, but
      at different rates, depending on post-mortem interval and soil temperature. In
      contrast to previous studies, we identified differential survival of nuclear and
      mtDNA in different tooth tissues. Furthermore histological examination showed
      pulp and dentine were rapidly affected by loss of structural integrity, and pulp
      was completely destroyed in a relatively short time period. Conversely, cementum
      showed little structural change over the same time period. Finally, we confirm
      that targeted sampling of cementum from teeth buried for up to 16 months can
      provide a reliable source of nuclear DNA for STR-based genotyping using standard
      extraction methods, without the need for specialised equipment or large-volume
      demineralisation steps.

PMID- 25992636
TI  - Tall guys and fat ladies: Grimaldi's Upper Paleolithic burials and figurines in
      an historical perspective.
AB  - The importance of the Grimaldi complex of caves and rock shelters is twofold:
      scientific and historical. Scientifically, it is one of the major Upper
      Paleolithic sites, considering the variety of mobiliary and parietal art, the
      number of single and multiple burials and associated grave goods, and the
      abundant lithic and fauna remains. Historically, the documentation of activity
      that took place in this site starting from the second half of the 19 th century
      and the studies carried out on the materials that have been recovered in the
      decades between 1870s-1910s, provide instructive examples of methods and goals of
      Paleolithic archeology and anthropology of the epoch. This paper combines the
      scientific and the historic interest of the site through a chronicle of the
      events that took place during the period of the most sensational discoveries,
      i.e. beginning with the identification in 1872 of the first Upper Paleolithic
      burial and ending with the results of the excavations carried out in 1901 at
      Grotte des Enfants published in four volumes a few years later. The paper
      discusses early interpretations and modern views on the different findings and
      documents changes in perspectives and goals of paleoanthropological research in
      over a century, raising some of the major issues of contemporary Upper
      Paleolithic studies. 

PMID- 25992637
TI  - Brains, teeth and life histories in hominins: a review.
AB  - The role of the brain in the somatic development, as well as in the establishment
      of the different variables of the life history pattern in vertebrates has been
      largely debated. Moreover, during the last thirty years, dental development has
      been used as a good proxy to infer different aspects of the life history in
      hominins, primarily due to the correlation that exists between age at first molar
      eruption and brain size in the order Primates. We review these questions using
      what is known about brain growth and maturation, dental development and life
      history pattern, mainly in Homo sapiens and Pan troglodytes. It has been assumed
      that the brain represents the pace-maker of our development. However, we consider
      that our particular phenotype is the result of a hierarchical genetic program
      modulated by epigenetic and environmental factors. The particular bauplan of any
      kind of organisms (e.g. primates) may explain the high correlation observed
      between different variables of its life history pattern, brain size or dental
      development. However, the correlation of these variables seems to be less
      reliable when dealing with low-rank taxonomical categories (i.e., species). We
      suggest that, while there is likely some relationship between the rate of somatic
      development and tooth development, our brain size and maturation (and, by
      extension, those of other species of the genus Homo) have derived towards a
      particular trajectory, with a unique pattern of prenatal and postnatal time and
      rate of growth and, particularly, with remarkable slow brain maturation. We
      suggest that extremely slow brain maturation could be a very recent acquisition
      of the last H. sapiens populations. Furthermore, our review of the literature
      suggests caution in drawing conclusions about aspects of the life history of the
      hominins from the information we can obtain from dental development in fossil
      specimens. 

PMID- 25992638
TI  - Body and head dimensions of adults in Sardinia (Italy) support different
      intensities of relative secular trends.

PMID- 25992640
TI  - Spatial Pattern of Attacks of the Invasive Woodwasp Sirex noctilio, at Landscape
      and Stand Scales.
AB  - Invasive insect pests are responsible for important damage to native and
      plantation forests, when population outbreaks occur. Understanding the spatial
      pattern of attacks by forest pest populations is essential to improve our
      understanding of insect population dynamics and for predicting attack risk by
      invasives or planning pest management strategies. The woodwasp Sirex noctilio is
      an invasive woodwasp that has become probably the most important pest of pine
      plantations in the Southern Hemisphere. Our aim was to study the spatial dynamics
      of S. noctilio populations in Southern Argentina. Specifically we describe: (1)
      the spatial patterns of S. noctilio outbreaks and their relation with
      environmental factors at a landscape scale; and (2) characterize the spatial
      pattern of attacked trees at the stand scale. We surveyed the spatial
      distribution of S. noctilio outbreaks in three pine plantation landscapes, and we
      assessed potential associations with topographic variables, habitat
      characteristics, and distance to other outbreaks. We also looked at the spatial
      distribution of attacked trees in 20 stands with different levels of infestation,
      and assessed the relationship of attacks with stand composition and management.
      We found that the spatial pattern of pine stands with S. noctilio outbreaks at
      the landscape scale is influenced mainly by the host species present, slope
      aspect, and distance to other outbreaks. At a stand scale, there is strong
      aggregation of attacked trees in stands with intermediate infestation levels, and
      the degree of attacks is influenced by host species and plantation management. We
      conclude that the pattern of S. noctilio damage at different spatial scales is
      influenced by a combination of both inherent population dynamics and the
      underlying patterns of environmental factors. Our results have important
      implications for the understanding and management of invasive insect outbreaks in
      forest systems. 

PMID- 25992639
TI  - Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of
      Interventions for the Prevention of Perinatal HIV.
AB  - BACKGROUND: Antiretroviral treatments decrease HIV mother-to-child transmission
      through pre/post exposure prophylaxis and reduction of maternal viral load. We
      modeled in-utero and intra-partum HIV transmissions to investigate the preventive
      role of various antiretroviral treatments interventions. METHODS: We analysed
      data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials
      evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose
      nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of
      mother-to-child transmission of HIV in Thailand. All infants were formula-fed.
      Non-linear mixed effect modeling was used to express the viral load evolution
      under antiretroviral treatments and the probability of transmission. RESULTS:
      Median viral load was 4 log10 copies/mL (Interquartile range: 3.36-4.56) before
      antiretroviral treatments initiation. An Emax model described the viral load time
      course during pregnancy. Half of the maximum effect of zidovudine (28% decrease)
      and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days,
      respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95%
      confidence interval: 1.34, 1.68] per log10 copies/mL increment), antiretroviral
      treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the
      nature of antiretroviral treatments were associated with in-utero transmission.
      Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]),
      baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm3 increment) and
      predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log10 copies/mL
      increment), single-dose nevirapine considerably reduced intra-partum transmission
      (OR = 0.32 [0.2, 0.51]). CONCLUSION: These models determined the respective
      contributions of various antiretroviral strategies on prevention of mother-to
      child transmission. This can help predict the efficacy of new antiretroviral
      treatments and/or prevention of mother-to-child transmission strategies
      particularly for women with no or late antenatal care who are at high risk of
      transmitting HIV to their offspring. TRIAL REGISTRATION: This analysis is based
      on secondary data obtained from three clinical trials. ClinicalTrials.gov.
      NCT00386230, NCT00398684, NCT00409591.

PMID- 25992641
TI  - The impact of lymphopenia on delirium in ICU patients.
AB  - BACKGROUND: Immunosuppressed states may predispose patients to development of
      acute brain injury during times of critical illness. Lymphopenia is a non
      specific yet commonly used bedside marker of immunosuppressed states. METHODS: We
      examined whether lymphopenia would predict development of acute brain dysfunction
      (delirium and/or coma) in 518 patients enrolled in the Bringing to Light the Risk
      Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN
      ICU) study in medical and surgical ICUs of a tertiary care, university-based
      medical center. Utilizing proportional odds logistic regression and Cox
      proportional hazards survival analysis, we assessed the relationship between pre
      enrollment lymphocytes and subsequent cognitive outcomes including delirium- and
      coma-free days (DCFDs) and 30-day mortality. RESULTS: There were no statistically
      significant associations between lymphocytes and DCFDs (p = 0.17); additionally,
      the relationship between lymphocytes and mortality was not statistically
      significant (p = 0.71). Among 259 patients without history of cancer or diabetes,
      there was no statistically significant association between lymphocytes and DCFDs
      (p = 0.07). CONCLUSION: lymphopenia, a commonly used bedside marker of
      immunosuppression, does not appear to be a marker of risk for acute brain injury
      (delirium/coma) or 30-day mortality in general medical/surgical ICU patients.

PMID- 25992643
TI  - Nanostructured Polyaniline Coating on ITO Glass Promotes the Neurite Outgrowth of
      PC 12 Cells by Electrical Stimulation.
AB  - A conducting polymer polyaniline (PANI) with nanostructure was synthesized on
      indium tin oxide (ITO) glass. The effect of electrical stimulation on the
      proliferation and the length of neurites of PC 12 cells was investigated. The
      dynamic protein adsorption on PANI and ITO surfaces in a cell culture medium was
      also compared with and without electrical stimulation. The adsorbed proteins were
      characterized using SDS-PAGE. A PANI coating on ITO surface was shown with 30-50
      nm spherical nanostructure. The number of PC 12 cells was significantly greater
      on the PANI/ITO surface than on ITO and plate surfaces after cell seeding for 24
      and 36 h. This result confirmed that the PANI coating is nontoxic to PC 12 cells.
      The electrical stimulation for 1, 2, and 4 h significantly enhanced the cell
      numbers for both PANI and ITO conducting surfaces. Moreover, the application of
      electrical stimulation also improved the neurite outgrowth of PC 12 cells, and
      the number of PC 12 cells with longer neurite lengths increased obviously under
      electrical stimulation for the PANI surface. From the mechanism, the adsorption
      of DMEM proteins was found to be enhanced by electrical stimulation for both
      PANI/ITO and ITO surfaces. A new band 2 (around 37 kDa) was observed from the
      collected adsorbed proteins when PC 12 cells were cultured on these surfaces, and
      culturing PC 12 cells also seemed to increase the amount of band 1 (around 90
      kDa). When immersing PANI/ITO and ITO surfaces in a DMEM medium without a cell
      culture, the number of band 3 (around 70 kDa) and band 4 (around 45 kDa) proteins
      decreased compared to that of PC 12 cell cultured surfaces. These results are
      valuable for the design and improvement of the material performance for neural
      regeneration. 

PMID- 25992642
TI  - Langerhans cell homeostasis and activation is altered in hyperplastic human
      papillomavirus type 16 E7 expressing epidermis.
AB  - It has previously been shown that expression of human papillomavirus type 16
      (HPV) E7 in epidermis causes hyperplasia and chronic inflammation,
      characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is
      strongly immune suppressed and is not rejected when transplanted onto immune
      competent mice. Professional antigen presenting cells are considered essential
      for initiation of the adaptive immune response that results in graft rejection.
      Langerhans cells (LC) are the only antigen presenting cells located in normal
      epidermis and altered phenotype and function of these cells may contribute to the
      immune suppressive microenvironment. Here, we show that LC are atypically
      activated as a direct result of E7 expression in the epidermis, and independent
      of the presence of lymphocytes. The number of LC was significantly increased and
      the LC are functionally impaired, both in migration and in antigen uptake.
      However when the LC were extracted from K14E7 skin and matured in vitro they were
      functionally competent to present and cross-present antigen, and to activate T
      cells. The ability of the LC to present and cross-present antigen following
      maturation supports retention of full functional capacity when removed from the
      hyperplastic skin microenvironment. As such, opportunities are afforded for the
      development of therapies to restore normal LC function in hyperplastic skin. 

PMID- 25992644
TI  - High prevalence of methicillin resistance and PVL genes among Staphylococcus
      aureus isolates from the nares and skin lesions of pediatric patients with atopic
      dermatitis.
AB  - Staphylococcus aureus is highly prevalent among patients with atopic dermatitis
      (AD), and this pathogen may trigger and aggravate AD lesions. The aim of this
      study was to determine the prevalence of S. aureus in the nares of pediatric
      subjects and verify the phenotypic and molecular characteristics of the isolates
      in pediatric patients with AD. Isolates were tested for antimicrobial
      susceptibility, SCCmec typing, and Panton-Valentine Leukocidin (PVL) genes.
      Lineages were determined by pulsed-field gel electrophoresis and multilocus
      sequence typing (MLST). AD severity was assessed with the Scoring Atopic
      Dermatitis (SCORAD) index. Among 106 patients, 90 (85%) presented S. aureus
      isolates in their nares, and 8 also presented the pathogen in their skin
      infections. Two patients had two positive lesions, making a total of 10 S. aureus
      isolates from skin infections. Methicillin-resistant S. aureus (MRSA) was
      detected in 24 (26.6%) patients, and PVL genes were identified in 21 (23.3%),
      including 6 (75%) of the 8 patients with skin lesions but mainly in patients with
      severe and moderate SCORAD values (P=0.0095). All 24 MRSA isolates were
      susceptible to trimethoprim/sulfamethoxazole, while 8 isolates had a minimum
      inhibitory concentration (MIC) to mupirocin >1024 MUg/mL. High lineage diversity
      was found among the isolates including USA1100/ST30, USA400/ST1, USA800/ST5,
      ST83, ST188, ST718, ST1635, and ST2791. There was a high prevalence of MRSA and
      PVL genes among the isolates recovered in this study. PVL genes were found mostly
      among patients with severe and moderate SCORAD values. These findings can help
      clinicians improve the therapies and strategies for the management of pediatric
      patients with AD. 

PMID- 25992648
TI  - A general theory of kinetics and thermodynamics of steady-state copolymerization.
AB  - Kinetics of steady-state copolymerization has been investigated since the 1940s.
      Irreversible terminal and penultimate models were successfully applied to a
      number of comonomer systems, but failed for systems where depropagation is
      significant. Although a general mathematical treatment of the terminal model with
      depropagation was established in the 1980s, a penultimate model and higher-order
      terminal models with depropagation have not been systematically studied, since
      depropagation leads to hierarchically-coupled and unclosed kinetic equations
      which are hard to solve analytically. In this work, we propose a truncation
      method to solve the steady-state kinetic equations of any-order terminal models
      with depropagation in a unified way, by reducing them into closed steady-state
      equations which give the exact solution of the original kinetic equations. Based
      on the steady-state equations, we also derive a general thermodynamic equality in
      which the Shannon entropy of the copolymer sequence is explicitly introduced as
      part of the free energy dissipation of the whole copolymerization system. 

PMID- 25992646
TI  - Protective roles of pulmonary rehabilitation mixture in experimental pulmonary
      fibrosis in vitro and in vivo.
AB  - Abnormal high mobility group protein B1 (HMGB1) activation is involved in the
      pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which
      combines extracts from eight traditional Chinese medicines, has very good lung
      protection in clinical use. However, it is not known if PRM has anti-fibrotic
      activity. In this study, we investigated the effects of PRM on transforming
      growth factor-beta1 (TGF-beta1)-mediated and bleomycin (BLM)-induced pulmonary
      fibrosis in vitro and in vivo. The effects of PRM on TGF-beta1-mediated
      epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of
      human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in
      vivo were investigated. PRM treatment resulted in a reduction of EMT in A549
      cells that was associated with attenuating an increase of vimentin and a decrease
      of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 ug/mL.
      PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of
      histopathological scores and collagen deposition, and a decrease in alpha-smooth
      muscle actin (alpha-SMA) and HMGB1 expression. An increase in receptor for
      advanced glycation end-product (RAGE) expression was found in BLM-instilled
      lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through
      decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF
      beta1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E
      cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by
      modulating the HMGB1/RAGE pathway. 

PMID- 25992645
TI  - Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients,
      is an indicator of malignancy.
AB  - Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion
      and urine. However, there is uncertainty about the localization of HA in tumor
      tissue and its relationship with different histological types and other
      components of the extracellular matrix, such as angiogenesis. We evaluated the
      association between HA and degree of malignancy through expression in lung tumor
      tissue and sputum. Tumoral tissue had significantly increased HA compared to
      normal tissue. Strong HA staining intensity associated with cancer cells was
      significant in squamous cell carcinoma compared to adenocarcinoma and large cell
      carcinoma. A significant direct association was found between tumors with a high
      percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly
      significant was the direct association between N1 tumors and high levels of HA in
      cancer cells. Cox multivariate analysis showed significant association between
      better survival and low HA. HA increased in sputum from lung cancer patients
      compared to cancer-free and healthy volunteers and a significant correlation was
      found between HA in sputum and HA in cancer tissue. Localization of HA in tumor
      tissue was related to malignancy and reflected in sputum, making this an emerging
      factor for an important diagnostic procedure in patients suspected to have lung
      cancer. Further study in additional patients in a randomized prospective trial is
      required to finalize these results and to validate our quantitative assessment of
      HA, as well as to couple it to gold standard sputum cytology. 

PMID- 25992649
TI  - Daytime Solar Heating Controls Downy Mildew Peronospora belbahrii in Sweet Basil.
AB  - The biotrophic oomycete Peronospora belbahrii causes a devastating downy mildew
      disease in sweet basil. Due to the lack of resistant cultivars current control
      measures rely heavily on fungicides. However, resistance to fungicides and strict
      regulation on their deployment greatly restrict their use. Here we report on a
      'green' method to control this disease. Growth chamber studies showed that P.
      belbahrii could hardly withstand exposure to high temperatures; exposure of
      spores, infected leaves, or infected plants to 35-45  degrees C for 6-9 hours
      suppressed its survival. Therefore, daytime solar heating was employed in the
      field to control the downy mildew disease it causes in basil. Covering growth
      houses of sweet basil already infected with downy mildew with transparent infra
      red-impermeable, transparent polyethylene sheets raised the daily maximal
      temperature during sunny hours by 11-22  degrees C reaching 40-58  degrees C
      (greenhouse effect). Such coverage, applied for a few hours during 1-3
      consecutive days, had a detrimental effect on the survival of P. belbahrii:
      killing the pathogen and/or suppressing disease progress while enhancing growth
      of the host basil plants.

PMID- 25992650
TI  - Correction: Evolutionary Patterns among Living and Fossil Kogiid Sperm Whales:
      Evidence from the Neogene of Central America.

PMID- 25992651
TI  - Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti
      Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT.
AB  - Due to the ongoing development of clinical photodynamic therapy (PDT), the search
      continues for optimized photosensitizers that can overcome some of the side
      effects associated with this type of treatment modality. The main protagonists
      being: post-treatment photosensitivity, due to only limited cellular selectivity
      and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory
      agents within the tumor microenvironment. A photosensitizer that could overcome
      one or both of these drawbacks would be highly attractive to those engaged in
      clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs) when used in
      combination with PDT have shown to increase the cytotoxicity of the treatment
      modality by targeting the tumor microenvironment. Temoporfin (m-THPC), the gold
      standard chlorin-based photosensitizer (PS) since its discovery in the 1980's,
      has successfully been conjugated to non-steroidal anti-inflammatory compounds, in
      an attempt to address the issue of post-treatment tumor regrowth. Using a
      modified Steglich esterification reaction, a library of "iPorphyrins" was
      successfully synthesized and evaluated for their PDT efficacy. 

PMID- 25992652
TI  - Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal
      Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis
      Congenita Patients.
AB  - Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome
      characterized by the presence of short telomeres at presentation. Mutations in
      ten different genes, whose products are involved in the telomere maintenance
      pathway, have been shown to cause DC. The X-linked form is the most common form
      of the disease and is caused by mutations in the gene DKC1, encoding the protein
      dyskerin. Dyskerin is required for the assembly and stability of telomerase and
      is also involved in ribosomal RNA (rRNA) processing where it converts specific
      uridines to pseudouridine. DC is thought to result from failure to maintain
      tissues, like blood, that are renewed by stem cell activity, but research into
      pathogenic mechanisms has been hampered by the difficulty of obtaining stem cells
      from patients. We reasoned that induced pluripotent stem (iPS) cells from X
      linked DC patients may provide information about the mechanisms involved. Here we
      describe the production of iPS cells from DC patients with DKC1 mutations Q31E,
      A353V and DeltaL37. In addition we constructed "corrected" lines with a copy of
      the wild type dyskerin cDNA expressed from the AAVS1 safe harbor locus. We show
      that in iPS cells with DKC1 mutations telomere maintenance is compromised with
      short telomere lengths and decreased telomerase activity. The degree to which
      telomere lengths are affected by expression of telomerase during reprograming, or
      with ectopic expression of wild type dyskerin, is variable. The recurrent
      mutation A353V shows the most severe effect on telomere maintenance. A353V cells
      but not Q31E or DeltaL37 cells, are refractory to correction by expression of
      wild type DKC1 cDNA. Because dyskerin is involved in both telomere maintenance
      and ribosome biogenesis it has been postulated that defective ribosome biogenesis
      and translation may contribute to the disease phenotype. Evidence from mouse and
      zebra fish models has supported the involvement of ribosome biogenesis but
      primary cells from human patients have so far not shown defects in
      pseudouridylation or ribosomal RNA processing. None of the mutant iPS cells
      presented here show decreased pseudouridine levels in rRNA or defective rRNA
      processing suggesting telomere maintenance defects account for most of the
      phenotype of X-linked DC. Finally gene expression analysis of the iPS cells shows
      that WNT signaling is significantly decreased in all mutant cells, raising the
      possibility that defective WNT signaling may contribute to disease pathogenesis. 

PMID- 25992654
TI  - The Long Noncoding RNA MEG3 Contributes to Cisplatin Resistance of Human Lung
      Adenocarcinoma.
AB  - Long noncoding RNAs (lncRNAs) have been identified as oncogenes or tumor
      suppressors that are involved in tumorigenesis and chemotherapy drug resistance.
      Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that
      encodes an lncRNA, and decreased MEG3 expression plays an important role in
      multiple cancers. However, its biological role in the development of the
      chemoresistance phenotype of human lung adenocarcinoma (LAD) is unknown. This
      study aimed to observe the expression of MEG3 in LAD and to evaluate its
      biological role and clinical significance in the resistance of LAD cells to
      cisplatin. MEG3 expression was markedly decreased in cisplatin-resistant A549/DDP
      cells compared with parental A549 cells as shown by an lncRNA microarray. MEG3
      overexpression in A549/DDP cells increased their chemosensitivity to cisplatin
      both in vitro and in vivo by inhibiting cell proliferation and inducing
      apoptosis. By contrast, MEG3 knockdown in A549 cells decreased the
      chemosensitivity. Moreover, MEG3 was decreased in cisplatin-insensitive LAD
      tissues while p53 protein levels were decreased and Bcl-xl protein levels
      increased. Furthermore, patients with lower levels of MEG3 expression showed
      worse responses to cisplatin-based chemotherapy. These findings demonstrate that
      MEG3 is significantly downregulated in LAD and partially regulates the cisplatin
      resistance of LAD cells through the control of p53 and Bcl-xl expression. Thus,
      MEG3 may represent a new marker of poor response to cisplatin and could be a
      potential therapeutic target for LAD chemotherapy. 

PMID- 25992656
TI  - Effects of a Six-Month Local Vibration Training on Bone Density, Muscle Strength,
      Muscle Mass, and Physical Performance in Postmenopausal Women.
AB  - The aim of the study was to investigate the effect of 6 months' local vibration
      training on bone mineral density (BMD), muscle strength, muscle mass, and
      physical performance in postmenopausal women (66-88 years). The study was
      organized as a randomized controlled trial for postmenopausal women who lived in
      daily care service flats and rest homes. Thirty-five postmenopausal women were
      randomly assigned to either a vibration (n = 17) or a control group (n = 18). The
      vibration group received 6-month local vibration treatment with frequency between
      30 and 45 Hz and acceleration between 1.71 and 3.58g. The vibration was applied
      on the midthigh and around the hip in supine-lying position once per day, 5 d.wk.
      The participants of the control group continued their usual activities and were
      not involved in any additional training program. The primary outcome variables
      were the isometric and dynamic quadriceps muscle strength and the BMD of the hip.
      We assessed the muscle mass of the quadriceps and physical performance.
      Additionally, the feasibility, side effects, and compliance were evaluated after
      6 months of local vibration training. Overall, the results showed a net benefit
      of 13.84% in isometric muscle strength at 60 degrees  knee angle in favor of the
      vibration group compared with controls (p < 0.01). No changes in BMD, muscle
      mass, or physical performance were found in both groups (p > 0.05). Six months of
      local vibration training improved some aspects of muscle strength but had no
      effect on BMD, muscle mass, and physical performance in postmenopausal women. The
      specific vibration protocol used in this study can be considered as safe and
      suitable for a local vibration training program.

PMID- 25992653
TI  - Characterization of the proteome of cytoplasmic lipid droplets in mouse
      enterocytes after a dietary fat challenge.
AB  - Dietary fat absorption by the small intestine is a multistep process that
      regulates the uptake and delivery of essential nutrients and energy. One step of
      this process is the temporary storage of dietary fat in cytoplasmic lipid
      droplets (CLDs). The storage and mobilization of dietary fat is thought to be
      regulated by proteins that associate with the CLD; however, mechanistic details
      of this process are currently unknown. In this study we analyzed the proteome of
      CLDs isolated from enterocytes harvested from the small intestine of mice
      following a dietary fat challenge. In this analysis we identified 181 proteins
      associated with the CLD fraction, of which 37 are associated with known lipid
      related metabolic pathways. We confirmed the localization of several of these
      proteins on or around the CLD through confocal and electron microscopy, including
      perilipin 3, apolipoprotein A-IV, and acyl-CoA synthetase long-chain family
      member 5. The identification of the enterocyte CLD proteome provides new insight
      into potential regulators of CLD metabolism and the process of dietary fat
      absorption. 

PMID- 25992655
TI  - A comprehensive review of swarm optimization algorithms.
AB  - Many swarm optimization algorithms have been introduced since the early 60's,
      Evolutionary Programming to the most recent, Grey Wolf Optimization. All of these
      algorithms have demonstrated their potential to solve many optimization problems.
      This paper provides an in-depth survey of well-known optimization algorithms.
      Selected algorithms are briefly explained and compared with each other
      comprehensively through experiments conducted using thirty well-known benchmark
      functions. Their advantages and disadvantages are also discussed. A number of
      statistical tests are then carried out to determine the significant performances.
      The results indicate the overall advantage of Differential Evolution (DE) and is
      closely followed by Particle Swarm Optimization (PSO), compared with other
      considered approaches. 

PMID- 25992657
TI  - Effect of Combined Sensorimotor-Resistance Training on Strength, Balance, and
      Jumping Performance of Soccer Players.
AB  - The purpose of the study was to investigate the effects of resistance training
      (RT) and sensorimotor training combined with RT (SM-RT) on balance, 1 repetition
      maximum (RM), rate of force development (RFD), and squat jump (SJ) height. Twenty
      amateur soccer players were equally divided into 2 groups assigned as SM-RT group
      (age: 22 +/- 1.7 years, body mass: 79.9 +/- 6.3 kg, body height: 1.81 +/- 0.06 m)
      and RT group (age: 21.3 +/- 1.3 years, body mass: 77.4 +/- 9.3 kg, body height:
      1.78 +/- 0.04 m). Both groups were trained over a 6-week period with 2 session
      units per week. SM-RT group performed sensorimotor training (balance on balance
      board) followed by a high-intensity RT at 8-5RM leg press. The RT group performed
      the resistance program only. Both groups showed significantly increased 1RM leg
      press strength, RFD, SJ height, and balance abilities (p <= 0.05), whereas no
      significant between-group differences were observed in any of the outcome
      variables (p > 0.05). It was concluded that SM-RT was not superior compared with
      RT for both balance and strength enhancement. These findings have implications in
      time management during training for soccer players.

PMID- 25992658
TI  - High-Intensity Resistance Exercise Promotes Postexercise Hypotension Greater than
      Moderate Intensity and Affects Cardiac Autonomic Responses in Women Who Are
      Hypertensive.
AB  - The purpose of this study was to evaluate the effect of high-intensity resistance
      exercise (RE) sessions on blood pressure (BP), heart rate (HR), cardiac autonomic
      modulation, and forearm blood flow (FBF). Sixteen trained hypertensive women (n =
      16, 56 +/- 3 years) completed the following 3 experimental sessions: control
      (CS), RE at 50% (EX50%), and RE at 80% (EX80%) of 1 repetition maximum (1RM).
      Both EX50% and EX80% comprised a set of 10 repetitions of 10 exercises, with an
      interval of 90 seconds between exercises. Measurements were taken preintervention
      and postintervention (at 10, 30, 50, 70, and 90 minutes of recovery). Reductions
      in systolic/diastolic BP after exercise were greater in EX80% (largest declines, 
      29 +/- 4/-14 +/- 5 mm Hg) than EX50% (largest declines, -18 +/- 6/-8 +/- 5 mm Hg,
      p <= 0.05). Heart rate and cardiac sympathovagal balance (LF/HF) increased more
      in relation to pre-exercise values in EX80% than EX50% (largest increases 96 +/-
      3 vs. 90 +/- 4 b.min, LF/HF = 1.77 +/- 0.25 vs. 1.40 +/- 0.20, respectively, p <=
      0.05). Increases in FBF and hyperemia was also higher in EX80% than EX50%
      compared with pre-exercise (4.97 +/- 0.28 vs. 4.36 +/- 0.27 ml.min.100 ml and
      5.90 +/- 0.20 vs. 5.38 +/- 0.25 ml.min.100 ml; p <= 0.05, respectively). These
      results suggest that RE of higher intensity promoted greater postexercise
      hypotension accompanied by greater increases in FBF, vasodilator response, HR,
      and cardiac sympathovagal balance.

PMID- 25992659
TI  - Anthropometric Characteristics and Performance Capabilities of Highly Trained
      Motocross Athletes Compared With Physically Active Men.
AB  - Motocross (MX) is a physically demanding sport with little research concerning
      the physiological characteristics of these athletes. The purpose of this study
      was to assess the anthropometric characteristics and performance capabilities of
      highly trained MX athletes (n = 20; 19 +/- 1.6 years) compared with age-matched
      physically active (PA) men (n = 22; 22 +/- 2.9 years). Testing was performed on 2
      occasions. The initial visit consisted of a personality assessment in addition to
      the following (in order): anthropometrics, body composition, anaerobic
      power/fatigue, isokinetic/isometric strength and fatigue, and flexibility. The
      second visit consisted of peak oxygen uptake (V[Combining Dot Above]O2peak),
      handgrip strength, maximum push-ups in 1 minute, extended arm hang time to
      exhaustion (TTE), and 90 degrees  weighted wall-sit tests. All anthropometric and
      performance data were analyzed using independent samples t-tests to compare group
      means. Significance was set at p <= 0.05. Data are reported as mean +/- SD. There
      were no significant differences between groups in anthropometric or body
      composition measurements except android fat (MX: 11.7 +/- 1.9% vs. PA: 16.4 +/-
      8.4%, p = 0.04) and biceps circumference (MX: 30.1 +/- 2.0 vs. PA: 33.1 +/- 3.2
      cm, p = 0.001). MX had significantly higher absolute and relative mean anaerobic
      power (747.3 +/- 63.7 vs. 679.7 +/- 93.5 W, p = 0.009 and 10.0 +/- 0.6 vs. 9.2 +/
      1.3 W.kg, p = 0.002, respectively), relative anaerobic peak power (12.7 +/- 0.8
      vs. 11.9 +/- 1.4 W.kg, p = 0.029), TTE (550.1 +/- 70.6 vs. 470.1 +/- 93.2
      seconds, p = 0.004), and extended arm hang duration (113.3 +/- 44.9 vs. 73.4 +/-
      25.3 seconds, p = 0.001). These results suggest highly trained MX athletes
      possess certain physiological adaptations that likely result from sport-specific
      demands compared with PA.

PMID- 25992660
TI  - The Foam Roll as a Tool to Improve Hamstring Flexibility.
AB  - Although foam rolling is a common myofascial therapy used to increase range of
      motion (ROM), research is limited on the effectiveness of foam rolling on soft
      tissue extensibility. The aim of this study was to determine the effect of a 4
      week training period of the foam roll method on hamstring flexibility.
      Furthermore, the study was designed to compare the effectiveness of the foam roll
      myofascial release with a conventional contract-relax proprioceptive
      neuromuscular facilitation (PNF) stretching method and a control group. Forty
      healthy males (age: 17-47 years) were randomly assigned to a foam roll group
      (FOAM, n = 13), a contract-relax PNF stretching group (CRPNF, n = 14), or a
      control group (CG, n = 13). The FOAM group massaged their hamstring muscles with
      the foam roll 3 times per week for 4 weeks (12 training sessions). The CRPNF
      group was assigned to 12 sessions of contract-relax PNF stretching. The CG
      underwent no intervention. Hamstring flexibility (ROM) was measured by a stand
      and-reach test before and after the intervention period. Two-way repeated
      measures analysis of variance showed a significant global time effect (p < 0.001)
      and an interaction effect for time * treatment (p = 0.004), demonstrating greater
      improvements in the FOAM and CRPNF compared with the CG, but no difference
      between the former. Delta changes from baseline to postintervention in ROM were
      not related to baseline ROM. The foam roll can be seen as an effective tool to
      increase hamstring flexibility within 4 weeks. The effects are comparable with
      the scientifically proven contract-relax PNF stretching method.

PMID- 25992661
TI  - Effects of Concurrent Activation Potentiation on Countermovement Jump
      Performance.
AB  - The purpose of this study was to assess the effects of concurrent activation
      potentiation (CAP) on countermovement jump (CMJ) performance. Twenty-four
      resistance-trained males (mean +/- SD; age: 25 +/- 4 years, body mass: 78.7 +/-
      10.3 kg) performed a CMJ on a force plate under 4 different conditions: (a) a
      control condition where the CMJ was performed with hands on hips and lips pursed,
      thus preventing jaw or fist contraction from occurring, (b) a jaw condition where
      the CMJ was performed with maximal contraction of the jaw, (c) a fist condition
      where the CMJ was performed with maximal contraction of the fists, and (d) a
      combined condition where the CMJ was performed with maximal contraction of both
      jaw and fists. Jump height (JH), peak force (PF), rate of force development
      (RFD), and time to peak force (TTPF) were calculated from the vertical force
      trace. There was no significant difference in PF (p = 0.88), TTPF (p = 0.96), JH
      (p = 0.45), or RFD (p = 0.06) between the 4 conditions. Effect size (ES)
      comparisons suggest a potential for CMJ with fist and jaw contraction (BOTH
      condition) to augment both PF (2.4%; ES: 0.62) and RFD (9.9%; ES: 0.94) over a
      normal CMJ (NORM condition). It is concluded that CAP by singular and combined
      contractions has no significant impact on CMJ performance; however, substantial
      interindividual variation in response to CAP was observed, and such techniques
      may therefore warrant consideration on an individual basis.

PMID- 25992662
TI  - Effect of an Ankle Compression Garment on Fatigue and Performance.
AB  - The aim of this study was to examine the effects of an ankle compression garment
      (CG) on muscle performance and physiological variables associated with recovery
      from fatigue. Fifteen participants took part in a randomized crossover study
      design with 2 experimental conditions (ankle CG and control). The dependent
      variables skin temperature, evoked muscle contractile properties, maximal
      voluntary contraction (MVC) force, electromyography (EMG), drop jump performance
      (20, 35, and 50 cm box heights), continuous drop jump (30 cm), time to fatigue
      (TTF), and blood lactate concentration were measured pre- and post-warm-up and
      postfatigue. Compared with control condition, ankle CG condition had
      significantly reduced half-relaxation times (p = 0.043) and higher skin
      temperatures at post-warm-up and post-fatigue protocol (p < 0.001, Delta3.2 and
      Delta4%, respectively). Participants also exhibited significantly lower ground
      reaction forces (GRFs) for 50-cm drop jumps (p = 0.044, Delta9.9%) with ankle CG
      at post-warm-up. There were no significant differences between conditions for
      muscle contractile properties, MVC force or EMG, jump height, take-off velocity,
      contact time, and jumping TTF. Independent of group, there was a threefold
      increase in blood lactate (p < 0.01) from pre-warm-up to post-fatigue and a
      significant decrease in MVC force (p = 0.048, Delta8.1%) from post-warm-up to
      postfatigue. Results suggest that ankle CG increased and maintained skin
      temperature during recovery, decreased twitch half-relaxation times, and reduced
      GRF from a 50-cm drop height. However, ankle CG did not improve other performance
      measures, aid in recovery, or affect blood lactate clearance.

PMID- 25992663
TI  - Biomechanical Factors Associated With Jump Height: A Comparison of Cross
      Sectional and Pre-to-Posttraining Change Findings.
AB  - Previous studies investigating the biomechanical factors associated with maximal
      countermovement jump height have typically used cross-sectional data. An
      alternative but less common approach is to use pre-to-posttraining change data,
      where the relationship between an improvement in jump height and a change in a
      factor is examined more directly. Our study compared the findings of these
      approaches. Such an evaluation is necessary because cross-sectional studies are
      currently a primary source of information for coaches when examining what factors
      to train to enhance performance. The countermovement jump of 44 males was
      analyzed before and after an 8-week training intervention. Correlations with jump
      height were calculated using both cross-sectional (pretraining data only) and pre
      to-posttraining change data. Eight factors identified in the cross-sectional
      analysis were not significantly correlated with a change in jump height in the
      pre-to-post analysis. Additionally, only 6 of 11 factors identified in the pre-to
      post analysis were identified in the cross-sectional analysis. These findings
      imply that (a) not all factors identified in a cross-sectional analysis may be
      critical to jump height improvement and (b) cross-sectional analyses alone may
      not provide an insight into all of the potential factors to train to enhance jump
      height. Coaches must be aware of these limitations when examining cross-sectional
      studies to identify factors to train to enhance jump ability. Additional findings
      highlight that although exercises prescribed to improve jump height should aim to
      enhance concentric power production at all joints, a particular emphasis on
      enhancing hip joint peak power may be warranted.

PMID- 25992664
TI  - Effect of Ambient Temperature on Pacing in Soccer Depends on Skill Level.
AB  - Link, D and Weber, H. Effect of ambient temperature on pacing in soccer depends
      on skill level. J Strength Cond Res 31(7): 1766-1770, 2017-This study examines
      the influence ambient temperature has on the distances covered by players in
      soccer matches. For this purpose, 1,211 games from the top German professional
      leagues were analyzed over the course of the seasons 2011/12 and 2012/13 using an
      optical tracking system. Data show (a) significant differences in the total
      distance covered (TDC, in meters per 10 minutes) between the 1. Bundesliga (M =
      1,225) and 2. Bundesliga (M = 1,201) and (b) a significant decrease in TDC from
      neutral (-4 to 13 degrees  C, M = 1,229) to warm (>=14 degrees  C, M = 1,217)
      environments. The size of the temperature effect is greater in the 1. Bundesliga
      (d = 0.30 vs. d = 0.16), although these players presumably have a higher level of
      fitness. This suggests that better players reduce their exertion level to a
      greater extent, thus preserving their ability to undertake the high-intensity
      activities when called upon. No reduction in running performance due to cold (<=5
      degrees  C) temperatures was observed.

PMID- 25992665
TI  - Intraoperative temperature management.

PMID- 25992666
TI  - Prevalence and distribution of Neospora caninum in water buffalo (Bubalus
      bubalis) and cattle in the Northern Territory of Australia.
AB  - The seroprevalence of Neospora caninum infection in water buffalo (Bubalus
      bubalis) and domestic cattle in the Northern Territory (NT) of Australia has
      never been determined. A total of 480 serum samples from water buffalo and 192
      serum samples from cattle, collected by the NT Government from 1993 through to
      2001, at 18 different survey sites throughout the Northern Territory were tested
      by commercial ELISA for anti-N. caninum antibodies. The water buffalo samples
      demonstrated a seroprevalence of 88.3% (95% CI +/- 2.9%), while 31.8% (+/-6.1%)
      of the cattle sera tested positive for N. caninum antibodies. Individual buffalo
      from the same herd, sampled over years, showed considerable fluctuations in S/P
      ratios. Overall, seropositivity was consistent across buffalo herds, and showed a
      slight decline over the years. The study presents evidence for the first time
      that N. caninum infection in water buffalo in the Northern Territory is a highly
      endemic and that infection rates are higher than those for cattle. This is
      important for an understanding of any potential sylvatic life cycle of N. caninum
      in Northern Australia. This survey also tests cattle from that territory for the
      first time for evidence of N. caninum infection and makes an important
      contribution to the understanding of disease management issues for the beef
      industry in the region. 

PMID- 25992667
TI  - Detecting deoxyhemoglobin in spinal cord vasculature of the experimental
      autoimmune encephalomyelitis mouse model of multiple sclerosis using
      susceptibility MRI and hyperoxygenation.
AB  - Susceptibility-weighted imaging (SWI) detects hypointensities due to iron
      deposition and deoxyhemoglobin. Previously it was shown that SWI detects
      hypointensities in the experimental autoimmune encephalomyelitis (EAE) model of
      multiple sclerosis (MS), most of which are due to intravascular deoxyhemoglobin,
      with a small proportion being due to iron deposition in the central nervous
      system parenchyma and demyelination. However, animals had to be sacrificed to
      differentiate these two types of lesions which is impractical for time course
      studies or for human application. Here, we proposed altering the inspired oxygen
      concentration during imaging to identify deoxyhemoglobin-based hypointensities in
      vivo. SWI was performed on lumbar spinal cords of naive control and EAE mice
      using 30% O2 then 100% O2. Some mice were imaged using 30% O2, 100% O2 and after
      perfusion. Most SWI-visible hypointensities seen with 30% O2 changed in
      appearance upon administration of 100% O2, and were not visible after perfusion.
      That hypointensities changed with hyperoxygenation indicates that they were
      caused by deoxyhemoglobin. We show that increasing the inspired oxygen
      concentration identifies deoxyhemoglobin-based hypointensities in vivo. This
      could be applied in future studies to investigate the contribution of vascular
      based hypointensities with SWI in EAE and MS over time. 

PMID- 25992668
TI  - Half-Sandwich Complexes of Dy(III): A Janus-Motif with Facile Tunability of
      Magnetism.
AB  - Three half-sandwich organometallics [(Cp(R))Dy(DBM)2(THF)].solvent [Cp(R) = Cp*
      (1Dy, Cp* = C5Me5), Cp(4PrPh) (2Dy, Cp(4PrPh) = C5Pr4Ph), Cp' (3Dy, Cp' =
      C5Me4TMS, solvent = THF), DBM(-) = dibenzoylmethanoate anion, THF =
      tetrahydrofuran, TMS = trimethylsilyl] with a Janus structural motif, where the
      ligands of DBM(-) and [Cp(R)](-) are widely used in Dy(III)/beta-diketonate and
      Ln(III)/cyclopentadienyl systems, were synthesized, structurally and magnetically
      characterized, and theoretically investigated. Single-crystal structural analysis
      reveals that the three complexes crystallize in the same space group P21/c. All
      the molecules display slow magnetic relaxation in the absence of an applied
      magnetic field, and the magnetic hysteresis loops of 2Dy and 3Dy can be observed
      under a magnetic field sweep rate of 10 Oe/s, indicating all three complexes are
      single-ion magnets (SIMs). The modifications of the Cp-ring lead to the distinct
      increment of the energy barrier from 46 K (1Dy) to 76 K (2Dy) to 320 K (3Dy). Ab
      initio calculations show that the ground Kramers doublet is strongly axial with
      gz approaching the value of 20 expected for the pure MJ = +/-15/2 state, and the
      magnetic anisotropy axes for three complexes share a similar orientation which is
      perpendicular to the molecular pseudosymmetric axis. Electrostatic analyses
      confirm the magnetic anisotropy orientations and reveal that proper charge
      distribution of the coordination sphere (including the first and second) around
      Dy(III) ion enhances the magnetic anisotropy. Further investigation of the
      relaxation mechanisms suggests the energy barrier should be carefully used to
      evaluate single-ion magnets if Raman process is dominant in the low temperature
      range. 

PMID- 25992669
TI  - Bees.

PMID- 25992670
TI  - Meet our prime pollinators.

PMID- 25992671
TI  - The beeline.

PMID- 25992672
TI  - Pesticides: Seeking answers amid a toxic debate.

PMID- 25992673
TI  - Microbiome: The puzzle in a bee's gut.

PMID- 25992674
TI  - Entomology: The bee-all and end-all.

PMID- 25992675
TI  - Animal behaviour: Nested instincts.

PMID- 25992676
TI  - Wild bees: Lone rangers.

PMID- 25992677
TI  - Aerodynamics: Vortices and robobees.

PMID- 25992678
TI  - Q&A: Charles Michener. A life with bees.

PMID- 25992679
TI  - Lipid bilayer crossing--the gate of symmetry. Water-soluble phenylproline-based
      blood-brain barrier shuttles.
AB  - Drug delivery to the brain can be achieved by various means, including blood
      brain barrier (BBB) disruption, neurosurgical-based approaches, and molecular
      design. Recently, passive diffusion BBB shuttles have been developed to transport
      low-molecular-weight drug candidates to the brain which would not be able to
      cross unaided. The low water solubility of these BBB shuttles has, however,
      prevented them from becoming a mainstream tool to deliver cargos across
      membranes. Here, we describe the design, synthesis, physicochemical
      characterization, and BBB-transport properties of phenylproline tetrapeptides,
      (PhPro)4, an improved class of BBB shuttles that operates via passive diffusion.
      These PhPro-based BBB shuttles showed 3 orders of magnitude improvement in water
      solubility compared to the gold-standard (N-MePhe)4, while retaining very high
      transport values. Transport capacity was confirmed when two therapeutically
      relevant cargos, nipecotic acid and l-3,4-dihydroxyphenylalanine (i.e., l-DOPA),
      were attached to the shuttle. Additionally, we used the unique chiral and
      conformationally restricted character of the (PhPro)4 shuttle to probe its chiral
      interactions with the lipid bilayer of the BBB. We studied the transport
      properties of 16 (PhPro)4 stereoisomers using the parallel artificial membrane
      permeability assay and looked at differences in secondary structure. Most
      stereoisomers displayed excellent transport values, yet this study also revealed
      pairs of enantiomers with high enantiomeric discrimination and different
      secondary structure, where one enantiomer maintained its high transport values
      while the other had significantly lower values, thereby confirming that
      stereochemistry plays a significant role in passive diffusion. This could open
      the door to the design of chiral and membrane-specific shuttles with potential
      applications in cell labeling and oncology. 

PMID- 25992680
TI  - Correction: A Decline in Benthic Foraminifera following the Deepwater Horizon
      Event in the Northeastern Gulf of Mexico.

PMID- 25992682
TI  - Premature birth as a risk factor for autism spectrum disorder.
AB  - OBJECTIVE: Autism spectrum disorder (ASD) is common, life-long in nature, and can
      be very debilitating. Thus, an intensive search is on to identify the potential
      risk factors for the disorder. Premature birth has been identified as one
      potential factor that could influence potential symptoms of ASD. METHOD: The
      sample for this study consisted of 1655 at risk children for developmental delays
      who were 17-37 months of age. Participants were divided into those diagnosed with
      ASD (n = 916) and children with atypical development only (n = 739). RESULTS:
      Premature births were almost twice as common for the atypical development group
      versus the ASD group. CONCLUSIONS: Implications of these data are discussed.

PMID- 25992683
TI  - Urticarial skin rash, fever, and arthralgia: a rare case of Schnitzler's
      syndrome.

PMID- 25992681
TI  - Adrenal Gland and Lung Lesions in Gulf of Mexico Common Bottlenose Dolphins
      (Tursiops truncatus) Found Dead following the Deepwater Horizon Oil Spill.
AB  - A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving
      primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and
      Alabama began in February 2010 and continued into 2014. Overlapping in time and
      space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed
      as a contributing cause of adrenal disease, lung disease, and poor health in live
      dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential
      contributing factors and causes of deaths for stranded UME dolphins from June
      2010 through December 2012, lung and adrenal gland tissues were histologically
      evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana
      (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were
      tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis.
      Results were compared to up to 106 fresh dead stranded dolphins from outside the
      UME area or prior to the DWH spill. UME dolphins were more likely to have primary
      bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin
      adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of
      UME dolphins with primary bacterial pneumonia, the condition either caused or
      contributed significantly to death. Brucellosis and morbillivirus infections were
      detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were
      low or below the detection limit, indicating that these were not primary causes
      of the current UME. The rare, life-threatening, and chronic adrenal gland and
      lung diseases identified in stranded UME dolphins are consistent with exposure to
      petroleum compounds as seen in other mammals. Exposure of dolphins to elevated
      petroleum compounds present in coastal GoM waters during and after the DWH oil
      spill is proposed as a cause of adrenal and lung disease and as a contributor to
      increased dolphin deaths. 

PMID- 25992684
TI  - Negative pressure wound therapy for treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and
      pressure injuries, are localised areas of injury to the skin or the underlying
      tissue, or both. Negative pressure wound therapy (NPWT) is a treatment option for
      pressure ulcers; a clear, current overview of the evidence is required to
      facilitate decision-making regarding its use. OBJECTIVES: To assess the effects
      of negative pressure wound therapy for treating pressure ulcers in any care
      setting. SEARCH METHODS: For this review, we searched the following databases in
      May 2015: 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. There were no restrictions based on language or date of publication.
      SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs)
      comparing the effects of NPWT with alternative treatments or different types of
      NPWT in the treatment of pressure ulcers (stage II or above). DATA COLLECTION AND
      ANALYSIS: Two review authors independently performed study selection, risk of
      bias assessment and data extraction. MAIN RESULTS: The review contains four
      studies with a total of 149 participants. Two studies compared NPWT with
      dressings; one study compared NPWT with a series of gel treatments and one study
      compared NPWT with 'moist wound healing'. One study had a 24-week follow-up
      period, and two had a six-week follow-up period, the follow-up time was unclear
      for one study. Three of the four included studies were deemed to be at a high
      risk of bias from one or more 'Risk of bias' domains and all evidence was deemed
      to be of very low quality. Only one study reported usable primary outcome data
      (complete wound healing), but this had only 12 participants and there were very
      few events (only one participant healed in the study). There was little other
      useful data available from the included studies on positive outcomes such as
      wound healing or negative outcomes such as adverse events. AUTHORS' CONCLUSIONS:
      There is currently no rigorous RCT evidence available regarding the effects of
      NPWT compared with alternatives for the treatment of pressure ulcers. High
      uncertainty remains about the potential benefits or harms, or both, of using this
      treatment for pressure ulcer management.

PMID- 25992685
TI  - Strategies for Selecting Routes through Real-World Environments: Relative
      Topography, Initial Route Straightness, and Cardinal Direction.
AB  - Previous research has demonstrated that route planners use several reliable
      strategies for selecting between alternate routes. Strategies include selecting
      straight rather than winding routes leaving an origin, selecting generally south-
      rather than north-going routes, and selecting routes that avoid traversal of
      complex topography. The contribution of this paper is characterizing the relative
      influence and potential interactions of these strategies. We also examine whether
      individual differences would predict any strategy reliance. Results showed
      evidence for independent and additive influences of all three strategies, with a
      strong influence of topography and initial segment straightness, and relatively
      weak influence of cardinal direction. Additively, routes were also
      disproportionately selected when they traversed relatively flat regions, had
      relatively straight initial segments, and went generally south rather than north.
      Two individual differences, extraversion and sense of direction, predicted the
      extent of some effects. Under real-world conditions navigators indeed consider a
      route's initial straightness, cardinal direction, and topography, but these cues
      differ in relative influence and vary in their application across individuals. 

PMID- 25992686
TI  - Generation and multi-phenotypic high-content screening of Coxiella burnetii
      transposon mutants.
AB  - Invasion and colonization of host cells by bacterial pathogens depend on the
      activity of a large number of prokaryotic proteins, defined as virulence factors,
      which can subvert and manipulate key host functions. The study of host/pathogen
      interactions is therefore extremely important to understand bacterial infections
      and develop alternative strategies to counter infectious diseases. This approach
      however, requires the development of new high-throughput assays for the unbiased,
      automated identification and characterization of bacterial virulence
      determinants. Here, we describe a method for the generation of a GFP-tagged
      mutant library by transposon mutagenesis and the development of high-content
      screening approaches for the simultaneous identification of multiple transposon
      associated phenotypes. Our working model is the intracellular bacterial pathogen
      Coxiellaburnetii, the etiological agent of the zoonosis Q fever, which is
      associated with severe outbreaks with a consequent health and economic burden.
      The obligate intracellular nature of this pathogen has, until recently, severely
      hampered the identification of bacterial factors involved in host pathogen
      interactions, making of Coxiella the ideal model for the implementation of high
      throughput/high-content approaches. 

PMID- 25992687
TI  - Leiomyomatosis peritonealis disseminata positive for progesterone receptor.
AB  - BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition
      that occurs in reproductive-age women. The pathogenesis of LPD is considered to
      be related to female sex hormones. CASE REPORT: A 30-year-old woman who had
      undergone an ovariectomy due to calcified thecoma at 24 years of age and had
      delivered a baby boy at 29 years of age showed abnormal abdominal-pelvic masses
      in a computed tomography scan. The peritoneal nodules were resected and
      histologically diagnosed as LPD. Smooth muscle cells in LPD lesions expressed
      progesterone receptor, while estrogen receptor and luteinizing hormone/chorionic
      gonadotropin receptor were negative. CONCLUSIONS: LPD should be considered when
      multiple nodules mimicking dissemination of malignancies are found in the
      abdominal cavity. In the present case, progesterone may have been involved in the
      pathogenesis of LPD.

PMID- 25992688
TI  - Ultrashort Echo Time T1rho Is Sensitive to Enzymatic Degeneration of Human
      Menisci.
AB  - OBJECTIVE: The aim of the study was to determine whether quantitative ultrashort
      echo time (UTE) -T1rho magnetic resonance (MR) measurements are sensitive to
      proteoglycan degradation in human menisci by trypsin digestion. METHODS:
      Conventional and quantitative UTE-T1rho MR sequences were performed on 4 meniscal
      samples using a 3T scanner. Magnetic resonance imaging was performed before and
      after 4, 8, and 12 hours of trypsin solution immersion, inducing proteoglycan
      loss. One sample was used as a control. Digest solutions were analyzed for
      glycosaminoglycan (GAG) content. The UTE-T1rho studies were analyzed for
      quantitative changes. RESULTS: Images showed progressive tissue swelling, fiber
      disorganization, and increase in signal intensity after GAG depletion. The UTE
      T1rho values tended to increase with time after trypsin treatment (P = 0.06).
      Cumulative GAG loss into the bath showed a trend of increased values for trypsin
      treated samples (P = 0.1). CONCLUSIONS: Ultrashort echo time T1rho measurements
      can noninvasively detect and quantify severity of meniscal degeneration, which
      has been correlated with progression of osteoarthritis.

PMID- 25992689
TI  - Elevation of SIPL1 (SHARPIN) Increases Breast Cancer Risk.
AB  - SIPL1 (Sharpin) or Sharpin plays a role in tumorigenesis. However, its
      involvement in breast cancer tumorigenesis remains largely unknown. To
      investigate this issue, we have systemically analyzed SIPL1 gene amplification
      and expression data available from Oncomine datasets, which were derived from 17
      studies and contained approximately 20,000 genes, 3438 breast cancer cases, and
      228 normal individuals. We found a SIPL1 gene amplification in invasive ductal
      breast cancers compared to normal breast tissues and a significant elevation of
      SIPL1 mRNA in breast cancers in comparison to non-tumor breast tissues. These
      results collectively reveal that increases in SIPL1 expression occur during
      breast cancer tumorigenesis. To further investigate this association, we observed
      increases in the SIPL1 gene and mRNA in the breast cancer subtypes of estrogen
      receptor (ER)+, progesterone receptor (PR)+, HER2+, or triple negative.
      Additionally, a gain of the SIPL1 gene correlated with breast cancer grade and
      the levels of SIPL1 mRNA associated with both breast cancer stages and grades.
      Elevation of SIPL1 gene copy and mRNA is linked to a decrease in patient
      survival, especially for those with PR+, ER+, or HER2- breast cancers. These
      results are supported by our analysis of SIPL1 protein expression using a tissue
      microarray containing 224 breast cancer cases, in which higher levels of SIPL1
      relate to ER+ and PR+ tumors and AKT activation. Furthermore, we were able to
      show that progesterone significantly reduced SIPL1 mRNA and protein expression in
      MCF7 cells. As progesterone enhances breast cancer tumorigenesis in a context
      dependent manner, inhibition of SIPL1 expression may contribute to progesterone's
      non-tumorigenic function which might be countered by SIPL1 upregulation. Taken
      together, we demonstrate a positive correlation of SIPL1 with BC tumorigenesis. 

PMID- 25992690
TI  - Anatomical network analysis shows decoupling of modular lability and complexity
      in the evolution of the primate skull.
AB  - Modularity and complexity go hand in hand in the evolution of the skull of
      primates. Because analyses of these two parameters often use different
      approaches, we do not know yet how modularity evolves within, or as a consequence
      of, an also-evolving complex organization. Here we use a novel network theory
      based approach (Anatomical Network Analysis) to assess how the organization of
      skull bones constrains the co-evolution of modularity and complexity among
      primates. We used the pattern of bone contacts modeled as networks to identify
      connectivity modules and quantify morphological complexity. We analyzed whether
      modularity and complexity evolved coordinately in the skull of primates.
      Specifically, we tested Herbert Simon's general theory of near-decomposability,
      which states that modularity promotes the evolution of complexity. We found that
      the skulls of extant primates divide into one conserved cranial module and up to
      three labile facial modules, whose composition varies among primates. Despite
      changes in modularity, statistical analyses reject a positive feedback between
      modularity and complexity. Our results suggest a decoupling of complexity and
      modularity that translates to varying levels of constraint on the morphological
      evolvability of the primate skull. This study has methodological and conceptual
      implications for grasping the constraints that underlie the developmental and
      functional integration of the skull of humans and other primates. 

PMID- 25992692
TI  - Has ethics changed or is it currently not being applied?

PMID- 25992691
TI  - Cilostazol attenuates ovariectomy-induced bone loss by inhibiting
      osteoclastogenesis.
AB  - BACKGROUND: Cilostazol has been reported to alleviate the metabolic syndrome
      induced by increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP)
      levels, which is also associated with osteoclast (OC) differentiation. We
      hypothesized that bone loss might be attenuated via an action on OC by
      cilostazol. METHODOLOGY AND PRINCIPAL FINDINGS: To test this idea, we
      investigated the effect of cilostazol on ovariectomy (OVX)-induced bone loss in
      mice and on OC differentiation in vitro, using MUCT and tartrate-resistant acid
      phosphatase staining, respectively. Cilostazol prevented from OVX-induced bone
      loss and decreased oxidative stress in vivo. It also decreased the number and
      activity of OC in vitro. The effect of cilostazol on reactive oxygen species
      (ROS) occurred via protein kinase A (PKA) and cAMP-regulated guanine nucleotide
      exchange factor 1, two major effectors of cAMP. Knockdown of NADPH oxidase using
      siRNA of p47phox attenuated the inhibitory effect of cilostazol on OC formation,
      suggesting that decreased OC formation by cilostazol was partly due to impaired
      ROS generation. Cilostazol enhanced phosphorylation of nuclear factor of
      activated T cells, cytoplasmic 1 (NFAT2) at PKA phosphorylation sites, preventing
      its nuclear translocation to result in reduced receptor activator of nuclear
      factor-kappaB ligand-induced NFAT2 expression and decreased binding of nuclear
      factor-kappaB-DNA, finally leading to reduced levels of two transcription factors
      required for OC differentiation. CONCLUSIONS/SIGNIFICANCE: Our data highlight the
      therapeutic potential of cilostazol for attenuating bone loss and oxidative
      stress caused by loss of ovarian function.

PMID- 25992693
TI  - Use of alcohol before and after bariatric surgery.
AB  - OBJECTIVE: to assess alcohol intake in the bariatric surgery pre and
      postoperative periods. METHODS: Patients were interviewed at Surgery Clinic of
      the Hospital das Clinicas da Universidade Federal de Pernambuco - HC/UFPE
      (Brazil) from July 2011 to March 2012. We analyzed socioeconomic, anthropometric
      and clinical variables. We used the Alcohol Use Disorders Identification Test
      (AUDIT C). RESULTS: One hundred nineteen patients were enrolled (mean age:
      41.23+11.30 years), with a predominance of the female gender (83.2%), non
      Caucasian race (55%), married individuals or in a stable union (65.5%), with a
      high school education (40.3%)and active in the job market (37%). Weight and body
      mass index (BMI) were 128.77+25.28 Kg and 49.09+9.26 Kg/m2,respectively in the
      preoperative period (class II obesity) and 87.19+19.16 Kg and 33.04+6.21 Kg/m2,
      respectively in the postoperative period (class I obesity) (p<0.001).
      Hypertension was the most frequent disease in the pre (66.6%) and postoperative
      (36.5%) periods. The prevalence of alcohol use was 26.6% in the preoperative
      period, of which 2.2% of high risk, and 35.1% in the postoperative period, of
      which 1.4% of probable dependence; this difference did not achieve statistical
      significance (p=0.337). CONCLUSION: The prevalence of abusive alcohol intake
      and/or probable dependence was low in both the pre and postoperative periods,
      with little evidence of risky consumption among the patients submitted to
      bariatric surgery.

PMID- 25992694
TI  - Assesment of the treatment of earlobe keloids with triamcinolone injections,
      surgical resection, and local pressure.
AB  - OBJECTIVE: To evaluate the combined treatment of ear lobe keloids. METHODS: We
      studied 46 consecutive patients with 81 ear lobe keloids. Patients underwent
      local infiltration of triamcinolone acetonide (TCN) at concentrations of 40 mg/ml
      (Group 1), 20 mg/ml (Group 2) and 10mg/ml (Group 3). The volume of TCN infiltrate
      varied according to the size of the lesion. Treatment consisted of three monthly
      injections before surgery, excision of keloid in the fourth month and
      perioperative infiltration, followed by two more leaks TCN within two months.
      Patients used earrings pressure on the scar after operation for four months. The
      pressure exerted by earrings in the ear lobe was measured electronically. Post
      treatment follow-up of patients was 24 months. RESULTS: TCN at concentrations of
      20mg/ml and 40 mg/ml were effective for the treatment of keloids, no difference
      between the groups (p = 0.58). However, patients in which TCN was infiltrated the
      10mg/ml had poor involution of keloid and the study of this group was stopped.
      CONCLUSION: the combination of infiltration TCN month to 20 mg/mL (1.2mg to 2.0mg
      per mm3 TCN injury), surgical excision and pressure application device is
      effective for treatment of keloid ear lobe.

PMID- 25992695
TI  - Submandibular gland excision.
AB  - OBJECTIVE: to analyze the value of fine needle aspiration and the rates of
      postoperative complications in patients undergoing resection of the submandibular
      gland. METHODS: we analyzed the records of patients treated with resection of the
      gland from January 1995 to December 2008. The data collected included age,
      gender, findings on clinical history, surgical procedure, results of fine needle
      aspiration (FNA), pathological diagnosis and complications. RESULTS: 117 patients
      were studied, aged 12-89 years (mean 48), 70 women and 47 men. Thirty-nine
      patients (33.3%) were affected by inflammatory diseases (28 patients with
      lithiasis), 70 had benign tumors, and malignant tumors, eight. Regarding FNA, the
      sensitivity and specificity were 85.7% and 100%, respectively. Nine patients
      (7.7%) had temporary paralysis of the marginal mandibular nerve and one had
      permanent paralysis. CONCLUSION: resection of the submandibular gland is a safe
      procedure, with low complication rates.

PMID- 25992696
TI  - Temporary abdominal closure with zipper-mesh device for management of intra
      abdominal sepsis.
AB  - OBJECTIVE: to present our experience with scheduled reoperations in 15 patients
      with intra-abdominal sepsis. METHODS: we have applied a more effective technique
      consisting of temporary abdominal closure with a nylon mesh sheet containing a
      zipper. We performed reoperations in the operating room under general anesthesia
      at an average interval of 84 hours. The revision consisted of debridement of
      necrotic material and vigorous lavage of the involved peritoneal area. The mean
      age of patients was 38.7 years (range, 15 to 72 years); 11 patients were male,
      and four were female. RESULTS: forty percent of infections were due to
      necrotizing pancreatitis. Sixty percent were due to perforation of the intestinal
      viscus secondary to inflammation, vascular occlusion or trauma. We performed a
      total of 48 reoperations, an average of 3.2 surgeries per patient. The mesh
      zipper device was left in place for an average of 13 days. An intestinal ostomy
      was present adjacent to the zipper in four patients and did not present a problem
      for patient management. Mortality was 26.6%. No fistulas resulted from this
      technique. When intra-abdominal disease was under control, the mesh-zipper device
      was removed, and the fascia was closed in all patients. In three patients, the
      wound was closed primarily, and in 12 it was allowed to close by secondary
      intent. Two patients developed hernia; one was incisional and one was in the
      drain incision. CONCLUSION: the planned reoperation for manual lavage and
      debridement of the abdomen through a nylon mesh-zipper combination was rapid,
      simple, and well-tolerated. It permitted effective management of severe septic
      peritonitis, easy wound care and primary closure of the abdominal wall.

PMID- 25992697
TI  - Resection of liver metastasis from neuroendocrine tumors: evaluation of results
      and prognostic factors.
AB  - OBJECTIVES: to determine the prognostic factors that may impact on morbidity and
      mortality and survival of patients undergoing surgical treatment of liver
      metastases from neuroendocrine tumors. METHODS: We studied 22 patients undergoing
      liver resection for metastases from neuroendocrine tumors between 1997 and 2007.
      Epidemiological and clinical data were correlated with morbidity and mortality
      and overall and disease-free survivals. RESULTS: twelve patients were male and
      ten female, with a mean age of 48.5 years. Bilobar disease was present in 17
      patients (77.3%). In ten patients (45.5%) the primary tumor originated in the
      pancreas, terminal ileum in eight, duodenum in two, rectum in one and jejunum in
      one. Complete surgical resection (R0) was achieved in 59.1% of patients. Eight
      patients (36.3%) developed complications in the immediate postoperative period,
      one of them dying from septicemia. All patients undergoing re-hepatectomy and/or
      two-stage hepatectomy had complications in the postoperative period. The overall
      survival at one and five years was 77.3% and 44.2%. The disease-free survival at
      five years was 13.6%. The primary pancreatic neuroendocrine tumor (p = 0.006) was
      associated with reduced overall survival. Patients with number of metastatic
      nodules < 10 (p = 0.03) and asymptomatic at diagnosis (p = 0.015) had higher
      disease-free survival. CONCLUSION: liver metastases originating from pancreatic
      neuroendocrine tumors proved to be a negative prognostic factor. Symptomatic
      patients with multiple metastatic nodules showed a significant reduction in
      disease-free survival.

PMID- 25992698
TI  - Comparative study of the different degrees of risk of gastrointestinal stromal
      tumor.
AB  - OBJECTIVE: To evaluate the applicability of the main categories of risk and
      morphological factors in the prognosis of gastrointestinal stromal tumors.
      METHODS: we retrospectively studied fifty-four cases of GIST, assessing the main
      prognostic factors of this neoplasis: risk levels, topography, size, mitotic
      index, necrosis, histological subtype and immunophenotype. We also verified their
      association and the reduction of overall survival. RESULTS: Univariate analysis
      showed that tumors with mitoses number greater than 5 per 50CGA (high-power
      fields), the presence of necrosis and a high risk for both the systems proposed
      by Fletcher and Miettinen had a significant association with reduced survival (p
      = 0.00001, 0.0056, 0.03 and 0.009, respectively). The remaining analyzed factors
      (size, histological subtype, topography and immunophenotype) had no such
      association. Multivariate analysis (Jacard index) showed that the Miettinen
      degree of risk was the one that best correlated with prognosis. CONCLUSION: the
      risk criteria of Fletcher and Miettinen are important in assessing the prognosis
      of patients with gastrointestinal stromal tumors, especially the latter, which
      adds to the mitotic index and the presence of tumor necrosis.

PMID- 25992699
TI  - Endovascular treatment of popliteal artery aneurysm. Early and midterm results.
AB  - OBJECTIVE: to evaluate the efficacy of endovascular repair of popliteal artery
      aneurysms on maintaining patency of the stent in the short and medium term.
      METHODS: this was a retrospective, descriptive and analytical study, conducted at
      the Integrated Vascular Surgery Service at the Hospital da Beneficencia
      Portuguesa de Sao Paulo. We followed-up 15 patients with popliteal aneurysm,
      totaling 18 limbs, treated with stent from May 2008 to December 2012. RESULTS:
      the mean follow-up was 14.8 months. During this period, 61.1% of the stents were
      patent. The average aneurysm diameter was 2.5 cm, ranging from 1.1 to 4.5 cm. The
      average length was 5 cm, ranging from 1.5 to 10 cm. In eight cases (47.1%), the
      lesion crossed the joint line, and in four of these occlusion of the prosthesis
      occurred. In 66.7% of cases, treatment was elective and only 33.3% were
      symptomatic patients treated on an emergency basis. The stents used were Viabahn
      (Gore) in 12 cases (66.7%), Fluency (Bard) in three cases (16.7%), Multilayer
      (Cardiatis) in two cases (11.1%) and Hemobahn (Gore) in one case (5.6%). In three
      cases, there was early occlusion (16.6%). During follow-up, 88.2% of patients
      maintained antiplatelet therapy. There was no leakage at ultrasound (endoleak).
      No fracture was observed in the stents. CONCLUSION: the results of this study are
      similar to other published series. Probably, with the development of new devices
      that support the mechanical characteristics found on the thighs, there will be
      improved performance and prognosis of endovascular restoration.

PMID- 25992700
TI  - Preliminary study of coconut water for graft tissues preservation in
      transplantation.
AB  - OBJECTIVE: to verify the effectiveness of coconut water in preserving tissues for
      transplant. METHODS: Fifty male Wistar rats were randomly distributed in five
      groups, according to the following preservation solutions for tissue grafts:
      Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut
      water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5,
      the green coconut water has been modified like the Belzer solution. From each
      animal we harvested the spleen, ovaries and skin of the back segment. These
      tissues were preserved for six hours in one of the solutions. Then, the grafts
      were reimplanted. The recovery of the function of the implanted tissues was
      assessed 90 days after surgery, by splenic scintigraphy and blood exam. The
      implanted tissues were collected for histopathological examination. RESULTS: The
      serum levels did not differ among groups, except for the animals in Group 5,
      which showed higher levels of IgG than Group 1, and differences in relation to
      FSH between groups 1 and 2 (p <0.001), 4 and 2 (p = 0.03) and 5 and 2 (p = 0.01).
      The splenic scintigraphy was not different between groups. The ovarian tissue was
      better preserved in mature coconut water (p <0.007). CONCLUSION: the coconut
      water-based solutions preserves spleen, ovary, and rat skin for six hours,
      maintaining their normal function.

PMID- 25992701
TI  - Use of the amniotic membrane to cover the peritoneal cavity in the reconstruction
      of the abdominal wall with polypropylene mesh in rats.
AB  - OBJECTIVE: to evaluate the efficacy of the amniotic membrane used with
      polypropylene mesh against the formation of adhesions and its influence on
      healing. METHODS: twenty five female Wistar rats were anesthetized for creating a
      parietal defect in the anterior abdominal wall. Its correction was made with
      polypropylene mesh alone and associated with amniotic membrane. In the control
      group (n=11), the screen was inserted alone. In group A (n=7) we interposed the
      amniotic membrane between the screen and the abdominal wall. In group B, the
      amniotic membrane was placed on the mesh, covering it. After seven days, the
      animals were euthanized for macroscopic and microscopic evaluation of healing.
      RESULTS: adhesions were observed in all animals except one in the control group.
      Severe inflammation was observed in all animals in groups A and B and in three of
      the control group, with significant difference between them (A and B with
      p=0.01). Pronounced angiogenic activity was noted in one animal in the control
      group, six in group A and four in group B, with a significant difference between
      the control group and group A (p=0.002) and group B (p=0.05). The scar collagen
      was predominantly mature, except in five animals of the control group, with
      significant difference between the control group and group A (p=0.05) and group B
      (p=0.05). CONCLUSION: The amniotic membrane did not alter the formation of
      adhesions in the first postoperative week. There were also pronounced
      inflammation, high angiogenic activity and predominance of mature collagen
      fibers, regardless of the anatomical plane that it was inserted in.

PMID- 25992702
TI  - Closure of large wounds using rubber bands in rabbits.
AB  - OBJECTIVE: to verify the effectiveness of the rubber elastic band in the
      treatment of large wounds of the body wall of rabbits by means of traction of its
      edges. METHODS: we studied 30 New Zealand rabbits, divided into three groups
      (n=10): Group 1- healing by secondary intention; Group 2- removal and eutopic
      repositioning of skin as full thickness skin graft; Group 3- Approximation of
      wound edges with elastic rubber band. In all animals, we removed a segment of the
      back skin and subcutaneous tissue down to the fascia, in accordance with an
      acrylic mold of 8 cm long by 12 cm wide. All animals were observed for 21 days.
      RESULTS: two animals of groups 1 and 2 had wound abscess. In Group 2, there was
      partial or total graft loss in 90% of animals. The complete closure of the wounds
      was observed in four animals of Group 1, six of Group 2 and eight of Group 3.
      There was no difference between the scar resistance values of groups 2 and 3,
      which were higher than those in Group 1. The scars of the three groups were
      characterized by the presence of mature connective tissue mixed with blood
      vessels and inflammatory infiltration, predominantly polymorphonuclear.
      CONCLUSION: the tensile strength of the wound edges with rubber elastic band is
      as efficient as the skin graft to treat rabbits' large body wounds.

PMID- 25992703
TI  - Importance of bone assessment and prevention of osteoporotic fracture in patients
      with prostate cancer in the gonadotropic hormone analogues use.
AB  - The antiandrogenic therapy (ADT) for prostate cancer represents an additional
      risk factor for the development of osteoporosis and fragility fractures. Still,
      bone health of patients on ADT is often not evaluated. After literature research
      we found that simple preventive measures can prevent bone loss in these patients,
      resulting in more cost-effective solutions to the public health system and family
      when compared to the treatment of fractures. 

PMID- 25992704
TI  - Treatment of gastrointestinal stromal tumor (GIST) during bariatric surgery.
AB  - The gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor. One should
      pay special attention when the GIST comes in obese patients during surgery. The
      laparoscopic resections with standard techniques, such as gastric bypass, have
      been described with good results. However, GIST resection associated sleeve
      gastrectomy for the treatment of obesity is rare, but can be done safely,
      depending on the location of the tumor. 

PMID- 25992705
TI  - Relevance of liver fat to the impact of dietary extrinsic sugars on lipid
      metabolism.
AB  - In contrast to the decline in mortality from many non-infectious, chronic
      diseases in the UK, death from liver disease has increased exponentially in men
      and women over the past 40 years. This is primarily because of the over
      consumption of alcohol, but also the increased prevalence of obesity, which is
      linked to early pathology through the accumulation of liver fat. Supra
      physiological intakes of fructose-containing sugar can produce acute, adverse
      effects on lipid metabolism, and deliver excess energy that increases bodyweight
      and the deposition of fat in sites other than adipose tissue, including the
      liver. This review addresses the variable metabolic origins of liver fat, and the
      key importance of postprandial lipid metabolism in this respect. The effects of
      supra-physiological intakes of sugar are also considered in context of the real
      world and established threshold for the adverse effects of sugar on cardio
      metabolic risk factors. The review concludes that while the average intake of
      sugar in the UK falls well below this critical threshold, intakes in subgroups of
      adults, and especially adolescents, may be cause for concern. There is also
      evidence to suggest that raised liver fat, acquired, in part, through an impaired
      removal of postprandial lipaemia, can increase sensitivity to the adverse effects
      of sugar at all ages. 

PMID- 25992707
TI  - Excited-State Vibrational Coherence in Perylene Bisimide Probed by Femtosecond
      Broadband Pump-Probe Spectroscopy.
AB  - Broadband laser pulses with ultrashort duration are capable of triggering
      impulsive excitation of the superposition of vibrational eigenstates, giving rise
      to quantum beating signals originating from coherent wave packet motions along
      the potential energy surface. In this work, coherent vibrational wave packet
      dynamics of an N,N'-bis(2,6-dimethylphenyl)perylene bisimide (DMP-PBI) were
      investigated by femtosecond broadband pump-probe spectroscopy which features fast
      and balanced data acquisition with a wide spectral coverage of >200 nm. Clear
      modulations were observed in the envelope of the stimulated emission decay
      profiles of DMP-PBI with the oscillation frequencies of 140 and 275 cm(-1). Fast
      Fourier transform analysis of each oscillatory mode revealed characteristic phase
      jumps near the maxima of the steady-state fluorescence, indicating that the
      observed vibrational coherence originates from an excited-state wave packet
      motion. Quantum calculations of the normal modes at the low-frequency region
      suggest that low-frequency C-C (C?C) stretching motions accompanied by
      deformation of the dimethylphenyl substituents are responsible for the
      manifestation of such coherent wave packet dynamics. 

PMID- 25992706
TI  - Cell context-specific expression of primary cilia in the human testis and ciliary
      coordination of Hedgehog signalling in mouse Leydig cells.
AB  - Primary cilia are sensory organelles that coordinate numerous cellular signalling
      pathways during development and adulthood. Defects in ciliary assembly or
      function lead to a series of developmental disorders and diseases commonly
      referred to as ciliopathies. Still, little is known about the formation and
      function of primary cilia in the mammalian testis. Here, we characterized primary
      cilia in adult human testis and report a constitutive expression of cilia in
      peritubular myoid cells and a dynamic expression of cilia in differentiating
      Leydig cells. Primary cilia are generally absent from cells of mature
      seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter
      syndrome testis. Peritubular cells in atrophic testis produce overly long cilia.
      Furthermore cultures of growth-arrested immature mouse Leydig cells express
      primary cilia that are enriched in components of Hedgehog signalling, including
      Smoothened, Patched-1, and GLI2, which are involved in regulating Leydig cell
      differentiation. Stimulation of Hedgehog signalling increases the localization of
      Smoothened to the cilium, which is followed by transactivation of the Hedgehog
      target genes, Gli1 and Ptch1. Our findings provide new information on the
      spatiotemporal formation of primary cilia in the testis and show that primary
      cilia in immature Leydig cells mediate Hedgehog signalling. 

PMID- 25992708
TI  - Autotaxin overexpression causes embryonic lethality and vascular defects.
AB  - Autotaxin (ATX) is a secretory protein, which converts lysophospholipids to
      lysophosphatidic acid (LPA), and is essential for embryonic vascular formation.
      ATX is abundantly detected in various biological fluids and its level is elevated
      in some pathophysiological conditions. However, the roles of elevated ATX levels
      remain to be elucidated. In this study, we generated conditional transgenic (Tg)
      mice overexpressing ATX and examined the effects of excess LPA signalling. We
      found that ATX overexpression in the embryonic period caused severe vascular
      defects and was lethal around E9.5. ATX was conditionally overexpressed in the
      neonatal period using the Cre/loxP system, which resulted in a marked increase in
      the plasma LPA level. This resulted in retinal vascular defects including
      abnormal vascular plexus and increased vascular regression. Our findings indicate
      that the ATX level must be carefully regulated to ensure coordinated vascular
      formation. 

PMID- 25992709
TI  - Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock
      Avoidance in Drosophila melanogaster.
AB  - Electric shock is a common stimulus for nociception-research and the most widely
      used reinforcement in aversive associative learning experiments. Yet, nothing is
      known about the mechanisms it recruits at the periphery. To help fill this gap,
      we undertook a genome-wide association analysis using 38 inbred Drosophila
      melanogaster strains, which avoided shock to varying extents. We identified 514
      genes whose expression levels and/ or sequences co-varied with shock avoidance
      scores. We independently scrutinized 14 of these genes using mutants, validating
      the effect of 7 of them on shock avoidance. This emphasizes the value of our
      candidate gene list as a guide for follow-up research. In addition, by
      integrating our association results with external protein-protein interaction
      data we obtained a shock avoidance-associated network of 38 genes. Both this
      network and the original candidate list contained a substantial number of genes
      that affect mechanosensory bristles, which are hair-like organs distributed
      across the fly's body. These results may point to a potential role for
      mechanosensory bristles in shock sensation. Thus, we not only provide a first
      list of candidate genes for shock avoidance, but also point to an interesting new
      hypothesis on nociceptive mechanisms. 

PMID- 25992710
TI  - Copper(II)-Catalyzed Direct Sulfonylation of C(sp(2))-H Bonds with Sodium
      Sulfinates.
AB  - A copper-catalyzed direct sulfonylation of C(sp(2))-H bonds with sodium
      sulfinates using a removable directing group is described. This reaction
      tolerates a wide range of functional groups, providing an efficient protocol for
      the synthesis of diverse aryl sulfones. Moreover, a series of 2,6-disubstituted
      benzamides could be synthesized via sequential C-H functionalization. 

PMID- 25992712
TI  - Ethylene/propylene copolymerization catalyzed by vanadium complexes containing N
      heterocyclic carbenes.
AB  - Various vanadium complexes containing N-heterocyclic carbenes, VOCl3[1,3
      R2(NCH=)2C:] (V1, R = 2,6-Me2C6H3; V2, R = 2,6-Et2C6H3; V3, R = 2,6-(i)Pr2C6H3;
      V4, R = 2,4,6-Me3C6H2), have been synthesized and employed as catalyst precursors
      for ethylene/propylene copolymerization after activation by Et3Al2Cl3. Complex V4
      showed higher catalytic activity of ca. 38 kg copolymer per (mol of V) per h and
      an ethylene/propylene copolymer with random monomer distribution could be
      prepared. Complex V3 consumed more cocatalyst than its analogues to reach higher
      catalytic activity. The obtained copolymers exhibit relatively narrow
      polydispersity and contain more randomly distributed monomer units than that the
      copolymers prepared by using the traditional vanadium catalytic system.

PMID- 25992711
TI  - Neuroanatomical substrates for the volitional regulation of heart rate.
AB  - The control of physiological arousal can assist in the regulation of emotional
      state. A subset cortical and subcortical brain regions are implicated in
      autonomic control of bodily arousal during emotional behaviors. Here, we combined
      human functional neuroimaging with autonomic monitoring to identify neural
      mechanisms that support the volitional regulation of heart rate, a process that
      may be assisted by visual feedback. During functional magnetic resonance imaging
      (fMRI), 15 healthy adults performed an experimental task in which they were
      prompted voluntarily to increase or decrease cardiovascular arousal (heart rate)
      during true, false, or absent visual feedback. Participants achieved appropriate
      changes in heart rate, without significant modulation of respiratory rate, and
      were overall not influenced by the presence of visual feedback. Increased
      activity in right amygdala, striatum and brainstem occurred when participants
      attempted to increase heart rate. In contrast, activation of ventrolateral
      prefrontal and parietal cortices occurred when attempting to decrease heart rate.
      Biofeedback enhanced activity within occipito-temporal cortices, but there was no
      significant interaction with task conditions. Activity in regions including
      pregenual anterior cingulate and ventral striatum reflected the magnitude of
      successful task performance, which was negatively related to subclinical anxiety
      symptoms. Measured changes in respiration correlated with posterior insula
      activation and heart rate, at a more lenient threshold, change correlated with
      insula, caudate, and midbrain activity. Our findings highlight a set of brain
      regions, notably ventrolateral prefrontal cortex, supporting volitional control
      of cardiovascular arousal. These data are relevant to understanding neural
      substrates supporting interaction between intentional and interoceptive states
      related to anxiety, with implications for biofeedback interventions, e.g., real
      time fMRI, that target emotional regulation. 

PMID- 25992713
TI  - Linearly Fused Azaacenes: Novel Approaches and New Applications Beyond Field
      Effect Transistors (FETs).
AB  - Replacing the CH groups in the backbones of acenes with heteroatoms offers
      scientists greater opportunities to tune their properties, as the type, position,
      number, and the valence of the introduced heteroatoms have strong effects on the
      frontier orbital energy levels. When the heteroatoms are nitrogen atoms, all of
      the resulting materials are called azaacenes. Recently, the synthesis, structure,
      physical properties, and applications of azaacene derivatives have been
      intensively investigated. This review focuses on recent synthetic efforts (since
      2013) toward making novel azaacenes as well as their potential applications
      beyond field-effect transistors (FETs) including organic light-emitting diodes
      (OLEDs), memory devices, phototransistors, solar cells, photoelectrical chemical
      cells, sensors, and conductors. 

PMID- 25992714
TI  - Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates
      Photoreceptor Loss in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis.
AB  - A sustained intraocular administration of neurotrophic factors is among the
      strategies aimed at establishing treatments for currently untreatable
      degenerative retinal disorders. In the present study we have analyzed the
      neuroprotective effects of a continuous neural stem (NS) cell-based intraocular
      delivery of ciliary neurotrophic factor (CNTF) on photoreceptor cells in the nclf
      mouse, an animal model of the neurodegenerative lysosomal storage disorder
      variant late infantile neuronal ceroid lipofuscinosis (vLINCL). To this aim, we
      genetically modified adherently cultivated NS cells with a polycistronic
      lentiviral vector encoding a secretable variant of CNTF together with a Venus
      reporter gene (CNTF-NS cells). NS cells for control experiments (control-NS
      cells) were modified with a vector encoding the reporter gene tdTomato. Clonal
      CNTF-NS and control-NS cell lines were established using fluorescent activated
      cell sorting and intravitreally grafted into 14 days old nclf mice at the onset
      of retinal degeneration. The grafted cells preferentially differentiated into
      astrocytes that were attached to the posterior side of the lenses and the vitreal
      side of the retinas and stably expressed the transgenes for at least six weeks,
      the latest post-transplantation time point analyzed. Integration of donor cells
      into host retinas, ongoing proliferation of grafted cells or adverse effects of
      the donor cells on the morphology of the host eyes were not observed.
      Quantitative analyses of host retinas two, four and six weeks after cell
      transplantation revealed the presence of significantly more photoreceptor cells
      in eyes with grafted CNTF-NS cells than in eyes with grafted control-NS cells.
      This is the first demonstration that a continuous intraocular administration of a
      neurotrophic factor attenuates retinal degeneration in an animal model of
      neuronal ceroid lipofuscinosis. 

PMID- 25992715
TI  - Short-range mobility and the evolution of cooperation: an experimental study.
AB  - A pressing issue in biology and social sciences is to explain how cooperation
      emerges in a population of self-interested individuals. Theoretical models
      suggest that one such explanation may involve the possibility of changing one's
      neighborhood by removing and creating connections to others, but this hypothesis
      has problems when random motion is considered and lacks experimental support. To
      address this, we have carried out experiments on diluted grids with human
      subjects playing a Prisoner's Dilemma. In contrast to previous results on
      purposeful rewiring in relational networks, we have found no noticeable effect of
      mobility in space on the level of cooperation. Clusters of cooperators form
      momentarily but in a few rounds they dissolve as cooperators at the boundaries
      stop tolerating being cheated upon. Our results highlight the difficulties that
      mobile agents have to establish a cooperative environment in a spatial setting. 

PMID- 25992716
TI  - Biomarkers With a Mechanistic Focus.

PMID- 25992717
TI  - Temperature differentially facilitates spontaneous but not evoked glutamate
      release from cranial visceral primary afferents.
AB  - Temperature is fundamentally important to all biological functions including
      synaptic glutamate release. Vagal afferents from the solitary tract (ST) synapse
      on second order neurons in the nucleus of the solitary tract, and glutamate
      release at this first central synapse controls autonomic reflex function.
      Expression of the temperature-sensitive Transient Receptor Potential Vanilloid
      Type 1 receptor separates ST afferents into C-fibers (TRPV1+) and A-fibers (TRPV1
      ). Action potential-evoked glutamate release is similar between C- and A-fiber
      afferents, but TRPV1 expression facilitates a second form of synaptic glutamate
      release in C-fibers by promoting substantially more spontaneous glutamate
      release. The influence of temperature on different forms of glutamate release is
      not well understood. Here we tested how temperature impacts the generation of
      evoked and spontaneous release of glutamate and its relation to TRPV1 expression.
      In horizontal brainstem slices of rats, activation of ST primary afferents
      generated synchronous evoked glutamate release (ST-eEPSCs) at constant latency
      whose amplitude reflects the probability of evoked glutamate release. The
      frequency of spontaneous EPSCs in these same neurons measured the probability of
      spontaneous glutamate release. We measured both forms of glutamate from each
      neuron during ramp changes in bath temperature of 4-5  degrees C. Spontaneous
      glutamate release from TRPV1+ closely tracked with these thermal changes
      indicating changes in the probability of spontaneous glutamate release. In the
      same neurons, temperature changed axon conduction registered as latency shifts
      but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These
      data indicate that TRPV1-operated glutamate release is independent of action
      potential-evoked glutamate release in the same neurons. Together, these support
      the hypothesis that evoked and spontaneous glutamate release originate from two
      pools of vesicles that are independently modulated and are distinct processes.

PMID- 25992719
TI  - Modeling macromolecular motions by x-ray-scattering-constrained molecular
      dynamics.

PMID- 25992718
TI  - Individually adapted imagery improves brain-computer interface performance in end
      users with disability.
AB  - Brain-computer interfaces (BCIs) translate oscillatory electroencephalogram (EEG)
      patterns into action. Different mental activities modulate spontaneous EEG
      rhythms in various ways. Non-stationarity and inherent variability of EEG
      signals, however, make reliable recognition of modulated EEG patterns
      challenging. Able-bodied individuals who use a BCI for the first time achieve -
      on average - binary classification performance of about 75%. Performance in users
      with central nervous system (CNS) tissue damage is typically lower. User training
      generally enhances reliability of EEG pattern generation and thus also robustness
      of pattern recognition. In this study, we investigated the impact of mental tasks
      on binary classification performance in BCI users with central nervous system
      (CNS) tissue damage such as persons with stroke or spinal cord injury (SCI).
      Motor imagery (MI), that is the kinesthetic imagination of movement (e.g.
      squeezing a rubber ball with the right hand), is the "gold standard" and mainly
      used to modulate EEG patterns. Based on our recent results in able-bodied users,
      we hypothesized that pair-wise combination of "brain-teaser" (e.g. mental
      subtraction and mental word association) and "dynamic imagery" (e.g. hand and
      feet MI) tasks significantly increases classification performance of induced EEG
      patterns in the selected end-user group. Within-day (How stable is the
      classification within a day?) and between-day (How well does a model trained on
      day one perform on unseen data of day two?) analysis of variability of mental
      task pair classification in nine individuals confirmed the hypothesis. We found
      that the use of the classical MI task pair hand vs. feed leads to significantly
      lower classification accuracy - in average up to 15% less - in most users with
      stroke or SCI. User-specific selection of task pairs was again essential to
      enhance performance. We expect that the gained evidence will significantly
      contribute to make imagery-based BCI technology become accessible to a larger
      population of users including individuals with special needs due to CNS damage. 

PMID- 25992720
TI  - The structure of a melittin-stabilized pore.
AB  - Melittin has been reported to form toroidal pores under certain conditions, but
      the atomic-resolution structure of these pores is unknown. A 9-MUs all-atom
      molecular-dynamics simulation starting from a closely packed transmembrane
      melittin tetramer in DMPC shows formation of a toroidal pore after 1 MUs. The
      pore remains stable with a roughly constant radius for the rest of the
      simulation. Surprisingly, one or two melittin monomers frequently transition
      between transmembrane and surface states. All four peptides are largely helical.
      A simulation in a DMPC/DMPG membrane did not lead to a stable pore, consistent
      with the experimentally observed lower activity of melittin on anionic membranes.
      The picture that emerges from this work is rather close to the classical toroidal
      pore, but more dynamic with respect to the configuration of the peptides. 

PMID- 25992721
TI  - Precision and variability in bacterial temperature sensing.
AB  - In Escherichia coli, the ratio of the two most abundant chemoreceptors, Tar/Tsr,
      has become the focus of much attention in bacterial taxis studies. This ratio has
      been shown to change under various growth conditions and to determine the
      response of the bacteria to the environment. Here, we present a study that makes
      a quantitative link between the ratio Tar/Tsr and the favored temperature of the
      cell in a temperature gradient and in various chemical environments. From the
      steady-state density-profile of bacteria with one dominant thermo-sensor, Tar or
      Tsr, we deduce the response function of each receptor to temperature changes.
      Using the response functions of both receptors, we determine the relationship
      between the favored temperature of wild-type bacteria with mixed clusters of
      receptors and the receptor ratio. Our model is based on the assumption that the
      behavior of a wild-type bacterium in a temperature gradient is determined by a
      linear combination of the independent responses of the two receptors, factored by
      the receptor's relative abundance in the bacterium. This is confirmed by
      comparing our model predictions with measurements of the steady-state density
      profile of several bacterial populations in a temperature gradient. Our results
      reveal that the density-profile of wild-type bacteria can be accurately described
      by measuring the distribution of the ratio Tar/Tsr in the population, which is
      then used to divide the population into groups with distinct Tar/Tsr values,
      whose behavior can be described in terms of independent Gaussian distributions.
      Each of these Gaussians is centered about the favored temperature of the
      subpopulation, which is determined by the receptor ratio, and has a width defined
      by the temperature-dependent speed and persistence time. 

PMID- 25992722
TI  - Cell shape dynamics reveal balance of elasticity and contractility in peripheral
      arcs.
AB  - The mechanical interaction between adherent cells and their substrate relies on
      the formation of adhesion sites and on the stabilization of contractile acto
      myosin bundles, or stress fibers. The shape of the cell and the orientation of
      these fibers can be controlled by adhesive patterning. On nonadhesive gaps,
      fibroblasts develop thick peripheral stress fibers, with a concave curvature. The
      radius of curvature of these arcs results from the balance of the line tension in
      the arc and of the surface tension in the cell bulk. However, the nature of these
      forces, and in particular the contribution of myosin-dependent contractility, is
      not clear. To get insight into the force balance, we inhibit myosin activity and
      simultaneously monitor the dynamics of peripheral arc radii and traction forces.
      We use these measurements to estimate line and surface tension. We found that
      myosin inhibition led to a decrease in the traction forces and an increase in arc
      radius, indicating that both line tension and surface tension dropped, but the
      line tension decreased to a lesser extent than surface tension. These results
      suggest that myosin-independent force contributes to tension in the peripheral
      arcs. We propose a simple physical model in which the peripheral arc line tension
      is due to the combination of myosin II contractility and a passive elastic
      component, while surface tension is largely due to active contractility.
      Numerical solutions of this model reproduce well the experimental data and allow
      estimation of the contributions of elasticity and contractility to the arc line
      tension. 

PMID- 25992723
TI  - Quantifying hydrostatic pressure in plant cells by using indentation with an
      atomic force microscope.
AB  - Plant cell growth depends on a delicate balance between an inner drive-the
      hydrostatic pressure known as turgor-and an outer restraint-the polymeric wall
      that surrounds a cell. The classical technique to measure turgor in a single
      cell, the pressure probe, is intrusive and cannot be applied to small cells. In
      order to overcome these limitations, we developed a method that combines
      quantification of topography, nanoindentation force measurements, and an
      interpretation using a published mechanical model for the pointlike loading of
      thin elastic shells. We used atomic force microscopy to estimate the elastic
      properties of the cell wall and turgor pressure from a single force-depth curve.
      We applied this method to onion epidermal peels and quantified the response to
      changes in osmolality of the bathing solution. Overall our approach is accessible
      and enables a straightforward estimation of the hydrostatic pressure inside a
      walled cell. 

PMID- 25992724
TI  - Efficient integration of synaptic events by NMDA receptors in three-dimensional
      neuropil.
AB  - Sustained activation of NMDA receptors (NMDARs) plays an important role in
      controlling activity of neural circuits in the brain. However, whether this
      activation reflects the ambient level of excitatory neurotransmitter glutamate in
      brain tissue or whether it depends mainly on local synaptic discharges remains
      poorly understood. To shed light on the underlying biophysics here we developed
      and explored a detailed Monte Carlo model of a realistic three-dimensional
      neuropil fragment containing 54 excitatory synapses. To trace individual
      molecules and their individual receptor interactions on this scale, we have
      designed and implemented a dedicated computer cluster and the appropriate
      software environment. Our simulations have suggested that sparse synaptic
      discharges are 20-30 times more efficient than nonsynaptic (stationary, leaky)
      supply of glutamate in controlling sustained NMDAR occupancy in the brain. This
      mechanism could explain how the brain circuits provide substantial background
      activation of NMDARs while maintaining a negligible ambient glutamate level in
      the extracellular space. Thus the background NMDAR occupancy, rather than the
      background glutamate level, is likely to reflect the ongoing activity in local
      excitatory networks. 

PMID- 25992725
TI  - Identification of the first sodium binding site of the phosphate cotransporter
      NaPi-IIa (SLC34A1).
AB  - Transporters of the SLC34 family (NaPi-IIa,b,c) catalyze uptake of inorganic
      phosphate (Pi) in renal and intestinal epithelia. The transport cycle requires
      three Na(+) ions and one divalent Pi to bind before a conformational change
      enables translocation, intracellular release of the substrates, and reorientation
      of the empty carrier. The electrogenic interaction of the first Na(+) ion with
      NaPi-IIa/b at a postulated Na1 site is accompanied by charge displacement, and
      Na1 occupancy subsequently facilitates binding of a second Na(+) ion at Na2. The
      voltage dependence of cotransport and presteady-state charge displacements (in
      the absence of a complete transport cycle) are directly related to the molecular
      architecture of the Na1 site. The fact that Li(+) ions substitute for Na(+) at
      Na1, but not at the other sites (Na2 and Na3), provides an additional tool for
      investigating Na1 site-specific events. We recently proposed a three-dimensional
      model of human SLC34a1 (NaPi-IIa) including the binding sites Na2, Na3, and Pi
      based on the crystal structure of the dicarboxylate transporter VcINDY. Here, we
      propose nine residues in transmembrane helices (TM2, TM3, and TM5) that
      potentially contribute to Na1. To verify their roles experimentally, we made
      single alanine substitutions in the human NaPi-IIa isoform and investigated the
      kinetic properties of the mutants by voltage clamp and (32)P uptake.
      Substitutions at five positions in TM2 and one in TM5 resulted in relatively
      small changes in the substrate apparent affinities, yet at several of these
      positions, we observed significant hyperpolarizing shifts in the voltage
      dependence. Importantly, the ability of Li(+) ions to substitute for Na(+) ions
      was increased compared with the wild-type. Based on these findings, we adjusted
      the regions containing Na1 and Na3, resulting in a refined NaPi-IIa model in
      which five positions (T200, Q206, D209, N227, and S447) contribute directly to
      cation coordination at Na1. 

PMID- 25992726
TI  - Membrane-mediated regulation of the intrinsically disordered CD3epsilon
      cytoplasmic tail of the TCR.
AB  - The regulation of T-cell-mediated immune responses depends on the phosphorylation
      of immunoreceptor tyrosine-based activation motifs (ITAMs) on T-cell receptors.
      Although many details of the signaling cascades are well understood, the initial
      mechanism and regulation of ITAM phosphorylation remains unknown. We used
      molecular dynamics simulations to study the influence of different compositions
      of lipid bilayers on the membrane association of the CD3epsilon cytoplasmic tails
      of the T-cell receptors. Our results show that binding of CD3epsilon to membranes
      is modulated by both the presence of negatively charged lipids and the lipid
      order of the membrane. Free-energy calculations reveal that the protein-membrane
      interaction is favored by the presence of nearby basic residues and the ITAM
      tyrosines. Phosphorylation minimizes membrane association, rendering the ITAM
      motif more accessible to binding partners. In systems mimicking biological
      membranes, the CD3epsilon chain localization is modulated by different
      facilitator lipids (e.g., gangliosides or phosphoinositols), revealing a
      plausible regulatory effect on activation through the regulation of lipid
      composition in cell membranes. 

PMID- 25992727
TI  - Interactions of the anticancer drug tamoxifen with lipid membranes.
AB  - Interactions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model
      membranes were studied using calcein-encapsulated vesicle leakage, attenuated
      total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle
      neutron scattering (SANS), atomic force microscopy (AFM) based force
      spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of
      TAM enhances membrane permeability, inducing calcein to translocate from the
      interior to the exterior of lipid vesicles. A large decrease in the FTIR
      absorption band's magnitude was observed in the hydrocarbon chain region,
      suggesting suppressed bond vibrational dynamics. Bilayer thickening was
      determined from SANS data. Force spectroscopy measurements indicate that the
      lipid bilayer area compressibility modulus KA is increased by a large amount
      after the incorporation of TAM. MD simulations show that TAM decreases the lipid
      area and increases chain order parameters. Moreover, orientational and positional
      analyses show that TAM exhibits a highly dynamic conformation within the lipid
      bilayer. Our detailed experimental and computational studies of TAM interacting
      with model lipid membranes shed new light on membrane modulation by TAM. 

PMID- 25992728
TI  - Deuterium NMR of raft model membranes reveals domain-specific order profiles and
      compositional distribution.
AB  - In this report, we applied site-specifically deuterated N-stearoylsphingomyelins
      (SSMs) to raft-exhibiting ternary mixtures containing SSM, 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC), and cholesterol (Chol) and successfully acquired
      deuterium quadrupole coupling profiles of SSM from liquid-ordered (Lo) and liquid
      disordered (Ld) domains. To our knowledge, this is the first report that shows
      detailed lipid chain dynamics separately and simultaneously obtained from
      coexisting Lo and Ld domains. We also found that the quadrupole profile of the Lo
      phase in the ternary system was almost identical to that in the SSM-Chol binary
      mixture, suggesting that the order profile of the binary system is essentially
      applicable to more complicated membrane systems in terms of the acyl chain order.
      We also demonstrated that (2)H NMR spectroscopy, in combination with organic
      synthesis of deuterated components, could be used to reveal the accurate mole
      fractions of each component distributed in the Lo and Ld domains. As compared
      with the reported tie-line analysis of phase diagrams, the merit of our (2)H NMR
      analysis is that the domain-specific compositional fractions are directly
      attainable without experimental complexity and ambiguity. The accurate
      compositional distributions as well as lipid order profiles in ternary mixtures
      are relevant to understanding the molecular mechanism of lipid raft formation. 

PMID- 25992729
TI  - Calcium binding promotes conformational flexibility of the neuronal Ca(2+) sensor
      synaptotagmin.
AB  - Synaptotagmin 1 (Syt1) is a synaptic vesicle protein that serves as a calcium
      sensor of neuronal secretion. It is established that calcium binding to Syt1
      triggers vesicle fusion and release of neuronal transmitters, however, the
      dynamics of this process is not fully understood. To investigate how Ca(2+)
      binding affects Syt1 conformational dynamics, we performed prolonged molecular
      dynamics (MD) simulations of Ca(2+)-unbound and Ca(2+)-bound forms of Syt1. MD
      simulations were performed at a microsecond scale and combined with Monte Carlo
      sampling. We found that in the absence of Ca(2+) Syt1 structure in the solution
      is represented by an ensemble of conformational states with tightly coupled
      domains. To investigate the effect of Ca(2+) binding, we used two different
      strategies to generate a molecular model of a Ca(2+)-bound form of Syt1. First,
      we employed subsequent replacements of monovalent cations transiently captured
      within Syt1 Ca(2+)-binding pockets by Ca(2+) ions. Second, we performed MD
      simulations of Syt1 at elevated Ca(2+) levels. All the simulations produced Syt1
      structures bound to four Ca(2+) ions, two ions chelated at the binding pocket of
      each domain. MD simulations of the Ca(2+)-bound form of Syt1 revealed that Syt1
      conformational flexibility drastically increased upon Ca(2+) binding. In the
      presence of Ca(2+), the separation between domains increased, and interdomain
      rotations became more frequent. These findings suggest that Ca(2+) binding to
      Syt1 may induce major changes in the Syt1 conformational state, which in turn may
      initiate the fusion process. 

PMID- 25992730
TI  - Fluorescence lifetime imaging of membrane lipid order with a ratiometric
      fluorescent probe.
AB  - To monitor the lateral segregation of lipids into liquid-ordered (Lo) and 
      disordered (Ld) phases in lipid membranes, environment-sensitive dyes that
      partition in both phases but stain them differently have been developed. Of
      particular interest is the dual-color F2N12S probe, which can discriminate the
      two phases through the ratio of its two emission bands. These bands are
      associated with the normal (N(*)) and tautomer (T(*)) excited-state species that
      result from an excited-state intramolecular proton transfer. In this work, we
      investigated the potency of the time-resolved fluorescence parameters of F2N12S
      to discriminate lipid phases in model and cell membranes. Both the long and mean
      lifetime values of the T(*) form of F2N12S were found to differ by twofold
      between Ld and Lo phases as a result of the restriction in the relative motions
      of the two aromatic moieties of F2N12S imposed by the highly packed Lo phase.
      This differed from the changes in the ratio of the two emission bands between the
      two phases, which mainly resulted from the decreased hydration of the N(*) form
      in the Lo phase. Importantly, the strong difference in lifetimes between the two
      phases was preserved when cholesterol was added to the Ld phase. The two phases
      could be imaged with high contrast by fluorescence lifetime imaging microscopy
      (FLIM) on giant unilamellar vesicles. FLIM images of F2N12S-labeled live HeLa
      cells confirmed that the plasma membrane was mainly in the Lo-like phase.
      Furthermore, the two phases were found to be homogeneously distributed all over
      the plasma membrane, indicating that they are highly mixed at the spatiotemporal
      resolution of the FLIM setup. Finally, FLIM could also be used to sensitively
      monitor the change in lipid phase upon cholesterol depletion and apoptosis. 

PMID- 25992731
TI  - DNA motion capture reveals the mechanical properties of DNA at the mesoscale.
AB  - Single-molecule studies probing the end-to-end extension of long DNAs have
      established that the mechanical properties of DNA are well described by a
      wormlike chain force law, a polymer model where persistence length is the only
      adjustable parameter. We present a DNA motion-capture technique in which DNA
      molecules are labeled with fluorescent quantum dots at specific sites along the
      DNA contour and their positions are imaged. Tracking these positions in time
      allows us to characterize how segments within a long DNA are extended by flow and
      how fluctuations within the molecule are correlated. Utilizing a linear response
      theory of small fluctuations, we extract elastic forces for the different, ~2-MUm
      long segments along the DNA backbone. We find that the average force-extension
      behavior of the segments can be well described by a wormlike chain force law with
      an anomalously small persistence length. 

PMID- 25992732
TI  - Swelling and softening of the cowpea chlorotic mottle virus in response to pH
      shifts.
AB  - Cowpea chlorotic mottle virus (CCMV) forms highly elastic icosahedral protein
      capsids that undergo a characteristic swelling transition when the pH is raised
      from 5 to 7. Here, we performed nano-indentation experiments using an atomic
      force microscope to track capsid swelling and measure the shells' Young's modulus
      at the same time. When we chelated Ca(2+) ions and raised the pH, we observed a
      gradual swelling of the RNA-filled capsids accompanied by a softening of the
      shell. Control experiments with empty wild-type virus and a salt-stable mutant
      revealed that the softening was not strictly coupled to the swelling of the
      protein shells. Our data suggest that a pH increase and Ca(2+) chelation lead
      primarily to a loosening of contacts within the protein shell, resulting in a
      softening of the capsid. This appears to render the shell metastable and make
      swelling possible when repulsive forces among the capsid proteins become large
      enough, which is known to be followed by capsid disassembly at even higher pH.
      Thus, softening and swelling are likely to play a role during inoculation. 

PMID- 25992733
TI  - Extending the range for force calibration in magnetic tweezers.
AB  - Magnetic tweezers are a wide-spread tool used to study the mechanics and the
      function of a large variety of biomolecules and biomolecular machines. This tool
      uses a magnetic particle and a strong magnetic field gradient to apply defined
      forces to the molecule of interest. Forces are typically quantified by analyzing
      the lateral fluctuations of the biomolecule-tethered particle in the direction
      perpendicular to the applied force. Since the magnetic field pins the anisotropy
      axis of the particle, the lateral fluctuations follow the geometry of a pendulum
      with a short pendulum length along and a long pendulum length perpendicular to
      the field lines. Typically, the short pendulum geometry is used for force
      calibration by power-spectral-density (PSD) analysis, because the movement of the
      bead in this direction can be approximated by a simple translational motion.
      Here, we provide a detailed analysis of the fluctuations according to the long
      pendulum geometry and show that for this direction, both the translational and
      the rotational motions of the particle have to be considered. We provide
      analytical formulas for the PSD of this coupled system that agree well with PSDs
      obtained in experiments and simulations and that finally allow a faithful
      quantification of the magnetic force for the long pendulum geometry. We
      furthermore demonstrate that this methodology allows the calibration of much
      larger forces than the short pendulum geometry in a tether-length-dependent
      manner. In addition, the accuracy of determination of the absolute force is
      improved. Our force calibration based on the long pendulum geometry will
      facilitate high-resolution magnetic-tweezers experiments that rely on short
      molecules and large forces, as well as highly parallelized measurements that use
      low frame rates. 

PMID- 25992734
TI  - Annealed random copolymer model of the B-Z transition in DNA: torsional
      responses.
AB  - Both in vivo and in vitro, specific sequences in double-stranded DNA can adopt
      the left-handed Z-form when underwound. Recently, the B-Z transition of DNA has
      been studied in detail in magnetic tweezers experiments by several groups. We
      present a theoretical description of this transition, based on an annealed random
      copolymer model. The transition of a switchable sequence is discussed as a
      function of energetic and geometric parameters of the B- and Z-forms, of the
      applied boundary conditions, and of the characteristics of the B-Z interface. We
      address a possible torsional softening upon the B-Z transition. The model can be
      also applied to other biofilaments with annealed torsional/flexural degrees of
      freedom. 

PMID- 25992735
TI  - Interpretation of solution x-ray scattering by explicit-solvent molecular
      dynamics.
AB  - Small- and wide-angle x-ray scattering (SWAXS) and molecular dynamics (MD)
      simulations are complementary approaches that probe conformational transitions of
      biomolecules in solution, even in a time-resolved manner. However, the structural
      interpretation of the scattering signals is challenging, while MD simulations
      frequently suffer from incomplete sampling or from a force-field bias. To combine
      the advantages of both techniques, we present a method that incorporates solution
      scattering data as a differentiable energetic restraint into explicit-solvent MD
      simulations, termed SWAXS-driven MD, with the aim to direct the simulation into
      conformations satisfying the experimental data. Because the calculations fully
      rely on explicit solvent, no fitting parameters associated with the solvation
      layer or excluded solvent are required, and the calculations remain valid at wide
      angles. The complementarity of SWAXS and MD is illustrated using three biological
      examples, namely a periplasmic binding protein, aspartate carbamoyltransferase,
      and a nuclear exportin. The examples suggest that SWAXS-driven MD is capable of
      refining structures against SWAXS data without foreknowledge of possible reaction
      paths. In turn, the SWAXS data accelerates conformational transitions in MD
      simulations and reduces the force-field bias. 

PMID- 25992736
TI  - Binding affinities controlled by shifting conformational equilibria:
      opportunities and limitations.
AB  - Conformational selection is an established mechanism in molecular recognition.
      Despite its power to explain binding events, it is hardly used in protein/ligand
      design to modulate molecular recognition. Here, we explore the opportunities and
      limitations of design by conformational selection. Using appropriate
      thermodynamic cycles, our approach predicts the effects of a conformational shift
      on binding affinity and also allows one to disentangle the effects induced by a
      conformational shift from other effects influencing the binding affinity. The
      method is assessed and applied to explain the contribution of a conformational
      shift on the binding affinity of six ubiquitin mutants showing different
      conformational shifts in six different complexes. 

PMID- 25992737
TI  - Topological polymorphism of the two-start chromatin fiber.
AB  - Specific details concerning the spatial organization of nucleosomes in 30 nm
      fibers remain unknown. To investigate this, we analyzed all stereochemically
      possible configurations of two-start nucleosome fibers with short DNA linkers L =
      13-37 bp (nucleosome repeat length (NRL) = 160-184 bp). Four superhelical
      parameters-inclination of nucleosomes, twist, rise, and diameter-uniquely
      describe a regular symmetric fiber. The energy of a fiber is defined as the sum
      of four terms: elastic energy of the linker DNA, steric repulsion,
      electrostatics, and a phenomenological (H4 tail-acidic patch) interaction between
      two stacked nucleosomes. By optimizing the fiber energy with respect to the
      superhelical parameters, we found two types of topological transition in fibers
      (associated with the change in inclination angle): one caused by an abrupt 360
      degrees  change in the linker DNA twisting (change in the DNA linking number,
      DeltaLk = 1), and another caused by overcrossing of the linkers (DeltaLk = 2). To
      the best of our knowledge, this topological polymorphism of the two-start fibers
      was not reported in the computations published earlier. Importantly, the optimal
      configurations of the fibers with linkers L = 10n and 10n + 5 bp are
      characterized by different values of the DNA linking number-that is, they are
      topologically different. Our results are consistent with experimental
      observations, such as the inclination 60 degrees  to 70 degrees  (the angle
      between the nucleosomal disks and the fiber axis), helical rise, diameter, and
      left-handedness of the fibers. In addition, we make several testable predictions,
      among them different degrees of DNA supercoiling in fibers with L = 10n and 10n +
      5 bp, different flexibility of the two types of fibers, and a correlation between
      the local NRL and the level of transcription in different parts of the yeast
      genome. 

PMID- 25992738
TI  - In vitro measurement of particle margination in the microchannel flow: effect of
      varying hematocrit.
AB  - It has long been known that platelets undergo margination when flowing in blood
      vessels, such that there is an excess concentration near the vessel wall. We
      conduct experiments and three-dimensional boundary integral simulations of
      platelet-sized spherical particles in a microchannel 30 MUm in height to measure
      the particle-concentration distribution profile and observe its margination at
      10%, 20%, and 30% red blood cell hematocrit. The experiments involved adding 2.15
      MUm-diameter spheres into a solution of red blood cells, plasma, and water and
      flowing this mixture down a microfluidic channel at a wall shear rate of 1000 s(
      1). Fluorescence imaging was used to determine the height and velocity of
      particles in the channel. Experimental results indicate that margination has
      largely occurred before particles travel 1 cm downstream and that hematocrit
      plays a role in the degree of margination. With simulations, we can track the
      trajectories of the particles with higher resolution. These simulations also
      confirm that margination from an initially uniform distribution of spheres and
      red blood cells occurs over the length scale of O(1 cm), with higher hematocrit
      showing faster margination. The results presented here, from both experiments and
      3D simulations, may help explain the relationship between bleeding time in vessel
      trauma and red blood cell hematocrit as platelets move to a vessel wall. 

PMID- 25992739
TI  - Isolation of Enteric Nervous System Progenitor Cells from the Aganglionic Gut of
      Patients with Hirschsprung's Disease.
AB  - Enteric nervous system progenitor cells isolated from postnatal human gut and
      cultured as neurospheres can then be transplanted into aganglionic gut to restore
      normal patterns of contractility. These progenitor cells may be of future use to
      treat patients with Hirschprung's disease, a congenital condition characterized
      by hindgut dysmotility due to the lack of enteric nervous system ganglia. Here we
      demonstrate that progenitor cells can also be isolated from aganglionic gut
      removed during corrective surgery for Hirschsprung's disease. Although the
      enteric nervous system marker calretinin is not expressed in the aganglionic gut
      region, de novo expression is initiated in cultured neurosphere cells isolated
      from aganglionic Hirschsprung bowel. Furthermore, expression of the neural
      markers NOS, VIP and GFAP also increased during culture of aganglionic gut
      neurospheres which we show can be transplantation into cultured embryonic mouse
      gut explants to restore a normal frequency of contractility. To determine the
      origin of the progenitor cells in aganglionic region, we used fluorescence
      activated cell sorting to demonstrate that only p75-positive neural crest-derived
      cells present in the thickened nerve trunks characteristic of the aganglionic
      region of Hirschsprung gut gave rise to neurons in culture. The derivation of
      enteric nervous system progenitors in the aganglionic gut region of Hirschprung's
      patients not only means that this tissue is a potential source of cells for
      future autologous transplantation, but it also raises the possibility of inducing
      the differentiation of these endogenous cells in situ to compensate for the
      aganglionosis. 

PMID- 25992740
TI  - Minimal invasive surgical procedure of inducing myocardial infarction in mice.
AB  - Myocardial infarction still remains the main cause of death in western countries,
      despite considerable progress in the stent development area in the last decades.
      For clarification of the underlying mechanisms and the development of new
      therapeutic strategies, the availability of valid animal models are mandatory.
      Since we need new insights into pathomechanisms of cardiovascular diseases under
      in vivo conditions to combat myocardial infarction, the validity of the animal
      model is a crucial aspect. However, protection of animals are highly relevant in
      this context. Therefore, we establish a minimally invasive and simple model of
      myocardial infarction in mice, which assures a high reproducibility and survival
      rate of animals. Thus, this models fulfils the requirements of the 3R principle
      (Replacement, Refinement and Reduction) for animal experiments and assure the
      scientific information needed for further developing of therapeutical strategies
      for cardiovascular diseases. 

PMID- 25992741
TI  - The fecal microbiome in cats with diarrhea.
AB  - Recent studies have revealed that microbes play an important role in the
      pathogenesis of gastrointestinal (GI) diseases in various animal species, but
      only limited data is available about the microbiome in cats with GI disease. The
      aim of this study was to evaluate the fecal microbiome in cats with diarrhea.
      Fecal samples were obtained from healthy cats (n = 21) and cats with acute (n =
      19) or chronic diarrhea (n = 29) and analyzed by sequencing of 16S rRNA genes,
      and PICRUSt was used to predict the functional gene content of the microbiome.
      Linear discriminant analysis (LDA) effect size (LEfSe) revealed significant
      differences in bacterial groups between healthy cats and cats with diarrhea. The
      order Burkholderiales, the families Enterobacteriaceae, and the genera
      Streptococcus and Collinsella were significantly increased in diarrheic cats. In
      contrast the order Campylobacterales, the family Bacteroidaceae, and the genera
      Megamonas, Helicobacter, and Roseburia were significantly increased in healthy
      cats. Phylum Bacteroidetes was significantly decreased in cats with chronic
      diarrhea (>21 days duration), while the class Erysipelotrichi and the genus
      Lactobacillus were significantly decreased in cats with acute diarrhea. The
      observed changes in bacterial groups were accompanied by significant differences
      in functional gene contents: metabolism of fatty acids, biosynthesis of
      glycosphingolipids, metabolism of biotin, metabolism of tryptophan, and ascorbate
      and aldarate metabolism, were all significantly (p<0.001) altered in cats with
      diarrhea. In conclusion, significant differences in the fecal microbiomes between
      healthy cats and cats with diarrhea were identified. This dysbiosis was
      accompanied by changes in bacterial functional gene categories. Future studies
      are warranted to evaluate if these microbial changes correlate with changes in
      fecal concentrations of microbial metabolites in cats with diarrhea for the
      identification of potential diagnostic or therapeutic targets. 

PMID- 25992743
TI  - The use of high-resolution infrared thermography (HRIT) for the study of ice
      nucleation and ice propagation in plants.
AB  - Freezing events that occur when plants are actively growing can be a lethal
      event, particularly if the plant has no freezing tolerance. Such frost events
      often have devastating effects on agricultural production and can also play an
      important role in shaping community structure in natural populations of plants,
      especially in alpine, sub-arctic, and arctic ecosystems. Therefore, a better
      understanding of the freezing process in plants can play an important role in the
      development of methods of frost protection and understanding mechanisms of freeze
      avoidance. Here, we describe a protocol to visualize the freezing process in
      plants using high-resolution infrared thermography (HRIT). The use of this
      technology allows one to determine the primary sites of ice formation in plants,
      how ice propagates, and the presence of ice barriers. Furthermore, it allows one
      to examine the role of extrinsic and intrinsic nucleators in determining the
      temperature at which plants freeze and evaluate the ability of various compounds
      to either affect the freezing process or increase freezing tolerance. The use of
      HRIT allows one to visualize the many adaptations that have evolved in plants,
      which directly or indirectly impact the freezing process and ultimately enables
      plants to survive frost events. 

PMID- 25992744
TI  - The CMS Innovation Center--a five-year self-assessment.

PMID- 25992745
TI  - Symbol of health system transformation? Assessing the CMS Innovation Center.

PMID- 25992747
TI  - Trends in mental health care among children and adolescents.
AB  - BACKGROUND: Increasing mental health treatment of young people and broadening
      conceptualizations of psychopathology have triggered concerns about a
      disproportionate increase in the treatment of youths with low levels of mental
      health impairment. METHODS: We analyzed the 1996-1998, 2003-2005, and 2010-2012
      Medical Expenditure Panel Surveys, which were nationally representative surveys
      of U.S. households, for trends in outpatient use of mental health services by
      persons 6 to 17 years of age; 53,622 persons were included in the analysis.
      Mental health impairment was measured with the use of the Columbia Impairment
      Scale (range, 0 to 52, with higher scores indicating more severe impairment); we
      classified youths with scores of 16 or higher as having more severe impairment
      and those with scores of less than 16 as having less severe impairment. RESULTS:
      The percentage of youths receiving any outpatient mental health service increased
      from 9.2% in 1996-1998 to 13.3% in 2010-2012 (odds ratio, 1.52; 95% confidence
      interval, 1.35 to 1.72). The proportionate increase in the use of mental health
      services among youths with more severe impairment (from 26.2% to 43.9%) was
      larger than that among youths with less severe or no impairment (from 6.7% to
      9.6%). However, the absolute increase in annual service use was larger among
      youths with less severe or no impairment (from 2.74 million to 4.19 million) than
      among those with more severe impairment (from 1.56 million to 2.28 million).
      Significant overall increases occurred in the use of psychotherapy (from 4.2% to
      6.0%) and psychotropic medications (from 5.5% to 8.9%), including stimulants and
      related medications (from 4.0% to 6.6%), antidepressants (from 1.5% to 2.6%), and
      antipsychotic drugs (from 0.2% to 1.2%). CONCLUSIONS: Outpatient mental health
      treatment and psychotropic-medication use in children and adolescents increased
      in the United States between 1996-1998 and 2010-2012. Although youths with less
      severe or no impairment accounted for most of the absolute increase in service
      use, youths with more severe impairment had the greatest relative increase in
      use, yet fewer than half accessed services in 2010-2012. (Funded by the Agency
      for Healthcare Research and Quality and the New York State Psychiatric
      Institute.).

PMID- 25992746
TI  - Trial of short-course antimicrobial therapy for intraabdominal infection.
AB  - BACKGROUND: The successful treatment of intraabdominal infection requires a
      combination of anatomical source control and antibiotics. The appropriate
      duration of antimicrobial therapy remains unclear. METHODS: We randomly assigned
      518 patients with complicated intraabdominal infection and adequate source
      control to receive antibiotics until 2 days after the resolution of fever,
      leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or
      to receive a fixed course of antibiotics (experimental group) for 4+/-1 calendar
      days. The primary outcome was a composite of surgical-site infection, recurrent
      intraabdominal infection, or death within 30 days after the index source-control
      procedure, according to treatment group. Secondary outcomes included the duration
      of therapy and rates of subsequent infections. RESULTS: Surgical-site infection,
      recurrent intraabdominal infection, or death occurred in 56 of 257 patients in
      the experimental group (21.8%), as compared with 58 of 260 patients in the
      control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence
      interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy
      was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as
      compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group
      (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant
      between-group differences were found in the individual rates of the components of
      the primary outcome or in other secondary outcomes. CONCLUSIONS: In patients with
      intraabdominal infections who had undergone an adequate source-control procedure,
      the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were
      similar to those after a longer course of antibiotics (approximately 8 days) that
      extended until after the resolution of physiological abnormalities. (Funded by
      the National Institutes of Health; STOP-IT ClinicalTrials.gov number,
      NCT00657566.).

PMID- 25992749
TI  - Images in clinical medicine. Verrucous tongue lesion.

PMID- 25992748
TI  - Pelvic inflammatory disease.

PMID- 25992751
TI  - Antibiotics for abdominal sepsis.

PMID- 25992750
TI  - Case records of the Massachusetts General Hospital. Case 16-2015. A 9-year-old
      girl with loss of consciousness and seizures.

PMID- 25992752
TI  - Beyond moral outrage--weighing the trade-offs of COI regulation.

PMID- 25992754
TI  - HIV-positive-to-HIV-positive kidney transplantation.

PMID- 25992753
TI  - HIV-positive-to-HIV-positive kidney transplantation.

PMID- 25992755
TI  - HIV-positive-to-HIV-positive kidney transplantation.

PMID- 25992756
TI  - HIV-positive-to-HIV-positive kidney transplantation.

PMID- 25992757
TI  - Driving pressure as a key ventilation variable.

PMID- 25992758
TI  - Driving pressure as a key ventilation variable.

PMID- 25992759
TI  - Driving pressure as a key ventilation variable.

PMID- 25992760
TI  - Driving pressure as a key ventilation variable.

PMID- 25992761
TI  - Natalizumab induction and maintenance therapy for Crohn's disease.

PMID- 25992762
TI  - Case 38-2014: An 87-year-old man with sore throat, hoarseness, fatigue, and
      dyspnea.

PMID- 25992763
TI  - Images in clinical medicine. Hemichoreoathetosis in neurosarcoidosis.

PMID- 25992764
TI  - Polymorphisms of Vascular Endothelial Growth Factor and Retinopathy of
      Prematurity.
AB  - PURPOSE: Retinopathy of prematurity (ROP) is a major problem among preterm
      survivors of neonatal intensive care. Neovascularization of the retina is
      prominent in the proliferative stages of ROP and is under the control of factors
      such as vascular endothelial growth factor (VEGF). The authors investigated the
      association of ROP with VEGF genetic polymorphisms and clinical (maternal,
      perinatal, neonatal) risk factors among preterm infants admitted to the neonatal
      intensive care unit. METHODS: The frequencies of VEGF 634 C/G and VEGF 936 C/T
      polymorphisms were determined in DNA from 102 preterm infants by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS:
      The frequency of the VEGF 634 CG genotype was significantly higher, whereas the
      frequency of the VEGF 634 CC genotype was significantly lower among neonates with
      ROP. The frequencies of the VEGF 634 GG, VEGF 936 CC, and VEGF 936 CT genotypes
      were similar in both groups. The distribution of VEGF 634 G allele was
      significantly different between the two groups. By logistic regression analysis,
      low birth weight, presence of maternal disease, respiratory distress syndrome,
      hypotension, and VEGF 634 CG genotype remained significant risk factors for the
      development of ROP. CONCLUSIONS: The results support the hypothesis that the
      carrier state of VEGF 634 C/G polymorphism has an impact on the risk of ROP in
      infants. A broader study may suggest that this marker could be used as an
      indicator in the screening for ROP.

PMID- 25992765
TI  - Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A
      Mimic of Childhood Granulomatosis With Polyangiitis.
AB  - IMPORTANCE: The type I interferonopathies comprise a recently recognized group of
      mendelian diseases characterized by an upregulation of type I interferon
      signaling. These monogenic phenotypes include classic Aicardi-Goutieres syndrome
      and syndromic forms of systemic lupus erythematosus, including familial chilblain
      lupus and spondyloenchondrodysplasia. Dermatologic features provide a major
      diagnostic clue to this disease grouping, as exemplified by the recently
      described stimulator of interferon genes-associated vasculopathy with onset in
      infancy (SAVI) caused by gain-of-function mutations in TMEM173. OBSERVATIONS: We
      describe a male child who, from the age of 2 months, had significant cutaneous
      disease that manifested as red violaceous plaques of the cheeks, nose, ears,
      fingers, and toes that progressed to gangrenous necrosis. In addition to his
      severe cutaneous vasculopathy, he experienced recurrent fevers, interstitial lung
      disease, and failure to thrive. His clinical syndrome was refractory to multiple
      immunosuppressive therapies. Evidence of marked upregulation of type I interferon
      signaling was observed in peripheral blood, and genetic testing identified a de
      novo germline mutation in TMEM173, confirming a diagnosis of SAVI 7 years after
      the onset of his disease. CONCLUSIONS AND RELEVANCE: This observational report
      describes a new case of SAVI, a recently defined monogenic inflammatory
      phenotype, that exemplifies an emerging group of disorders related to primary
      upregulation of type I interferon signaling.

PMID- 25992766
TI  - Ultrasound in dual nerve impairment after proximal radial nerve lesion.
AB  - INTRODUCTION: Sonography in classical nerve entrapment syndromes is an
      established and validated method. In contrast, few publications highlight lesions
      of the radial nerve, particularly of the posterior interosseus nerve (PIN).
      METHOD: Five patients with a radial nerve lesion were investigated by
      electromyography, nerve conduction velocity and ultrasound. Further normative
      values of 26 healthy subjects were evaluated. RESULTS: Four patients presented a
      clinical and electrophysiological proximal axonal radial nerve lesion and one
      patient showed a typical posterior interosseous nerve syndrome (PINS). The
      patient with PINS presented an enlargement of the PIN anterior to the supinator
      muscle. However four patients with proximal lesions showed an unexpected
      significant enlargement of the PIN within the supinator muscle. CONCLUSION: High
      resolution sonography is a feasible method to demonstrate the radial nerve
      including its distal branches. At least in axonal radial nerve lesions,
      sonography might reveal abnormalities far distant from a primary proximal lesion
      site clearly distinct from the appearance in classical PINS.

PMID- 25992767
TI  - Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic
      meta-analysis.
AB  - Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention
      because of its physiological and pharmacological implications; however, a clear
      definition of tissue RAAS is still missing. We aimed to establish a preliminary
      atlas for the organization of RAAS across 23 different normal human tissues. A
      set of 37 genes encoding classical and novel RAAS participants including gluco-
      and mineralo-corticoids were defined as extended RAAS (extRAAS) system.
      Microarray data sets containing more than 10 normal tissues were downloaded from
      the GEO database. R software was used to extract expression levels and construct
      dendrograms of extRAAS genes within each data set. Tissue co-expression modules
      were then extracted from reproducible gene clusters across data sets. An atlas of
      the maps of tissue-specific organization of extRAAS was constructed from gene
      expression and coordination data. Our analysis included 143 data sets containing
      4933 samples representing 23 different tissues. Expression data provided an
      insight on the favored pathways in a given tissue. Gene coordination indicated
      the existence of tissue-specific modules organized or not around conserved core
      groups of transcripts. The atlas of tissue-specific organization of extRAAS will
      help better understand tissue-specific effects of RAAS. This will provide a frame
      for developing more effective and selective pharmaceuticals targeting extRAAS. 

PMID- 25992768
TI  - Lepr(db) mouse model of type 2 diabetes: pancreatic islet isolation and live-cell
      2-photon imaging of intact islets.
AB  - Type 2 diabetes is a chronic disease affecting 382 million people in 2013, and is
      expected to rise to 592 million by 2035 (1). During the past 2 decades, the role
      of beta-cell dysfunction in type 2 diabetes has been clearly established (2).
      Research progress has required methods for the isolation of pancreatic islets.
      The protocol of the islet isolation presented here shares many common steps with
      protocols from other groups, with some modifications to improve the yield and
      quality of isolated islets from both the wild type and diabetic Lepr(db) (db/db)
      mice. A live-cell 2-photon imaging method is then presented that can be used to
      investigate the control of insulin secretion within islets. 

PMID- 25992769
TI  - A novel immunochromatographic test applied to a serological survey of Japanese
      encephalitis virus on pig farms in Korea.
AB  - Among vertebrate species, pigs are a major amplifying host of Japanese
      encephalitis virus (JEV) and measuring their seroconversion is a reliable
      indicator of virus activity. Traditionally, the hemagglutination inhibition test
      has been used for serological testing in pigs; however, it has several
      limitations and, thus, a more efficient and reliable replacement test is
      required. In this study, we developed a new immunochromatographic test for
      detecting antibodies to JEV in pig serum within 15 min. Specifically, the domain
      III region of the JEV envelope protein was successfully expressed in soluble form
      and used for developing the immunochromatographic test. The test was then applied
      to the surveillance of Japanese encephalitis (JE) in Korea. We found that our
      immunochromatographic test had good sensitivity (84.8%) and specificity (97.7%)
      when compared with an immunofluorescence assay used as a reference test. During
      the surveillance of JE in Korea in 2012, the new immunochromatographic test was
      used to test the sera of 1,926 slaughtered pigs from eight provinces, and 228
      pigs (11.8%) were found to be JEV-positive. Based on these results, we also
      produced an activity map of JEV, which marked the locations of pig farms in Korea
      that tested positive for the virus. Thus, the immunochromatographic test reported
      here provides a convenient and effective tool for real-time monitoring of JEV
      activity in pigs. 

PMID- 25992770
TI  - Near infrared photoimmunotherapy prevents lung cancer metastases in a murine
      model.
AB  - Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that
      combines the specificity of intravenously injected antibodies with the acute
      toxicity induced by photosensitizers after exposure to NIR-light. Herein, we
      evaluate the efficacy of NIR-PIT in preventing lung metastases in a mouse model.
      Lung is one of the most common sites for developing metastases, but it also has
      the deepest tissue light penetration. Thus, lung is the ideal site for treating
      early metastases by using a light-based strategy. In vitro NIR-PIT cytotoxicity
      was assessed with dead cell staining, luciferase activity, and a decrease in
      cytoplasmic GFP fluorescence in 3T3/HER2-luc-GFP cells incubated with an anti
      HER2 antibody photosensitizer conjugate. Cell-specific killing was demonstrated
      in mixed 2D/3D cell cultures of 3T3/HER2-luc-GFP (target) and 3T3-RFP (non
      target) cells. In vivo NIR-PIT was performed in the left lung in a mouse model of
      lung metastases, and the number of metastasis nodules, tumor fluorescence, and
      luciferase activity were all evaluated. All three evaluations demonstrated that
      the NIR-PIT-treated lung had significant reductions in metastatic disease (*p <
      0.0001, Mann-Whitney U-test) and that NIR-PIT did not damage non-target tumors or
      normal lung tissue. Thus, NIR-PIT can specifically prevent early metastases and
      is a promising anti-metastatic therapy. 

PMID- 25992771
TI  - Combined targeting of EGFR/HER promotes anti-tumor efficacy in subsets of KRAS
      mutant lung cancer resistant to single EGFR blockade.
AB  - KRAS is a frequently mutated oncogene in lung cancer and among the most
      refractory to EGFR targeted therapy. Recently, preclinical evidence in pancreatic
      cancer has demonstrated that mutant KRAS can be regulated by EGFR. However, the
      distinct correlation between the EGFR/HER family members and mutant KRAS has not
      been investigated. Here, we show that non-small cell lung cancer cell lines
      harboring differing isoforms of mutant KRAS, can be broadly divided into EGFR/HER
      dependent and EGFR/HER independent groups. Combined therapeutic targeting of
      EGFR, HER2 and HER3 in isoforms regulated by extracellular growth signals
      promotes in vitro and in vivo efficacy. We also provide evidence that depletion
      of EGFR via RNA interference specifically abolishes the EGFR/KRAS interaction in
      the dependent subset. Taken together, these findings suggest that upstream
      inhibition of the EGFR/HER receptors may be effective in treating a subset of
      KRAS mutant lung cancers.

PMID- 25992772
TI  - Kras activation in p53-deficient myoblasts results in high-grade sarcoma
      formation with impaired myogenic differentiation.
AB  - While genomic studies have improved our ability to classify sarcomas, the
      molecular mechanisms involved in the formation and progression of many sarcoma
      subtypes are unknown. To better understand developmental origins and genetic
      drivers involved in rhabdomyosarcomagenesis, we describe a novel sarcoma model
      system employing primary murine p53-deficient myoblasts that were isolated and
      lentivirally transduced with KrasG12D. Myoblast cell lines were characterized and
      subjected to proliferation, anchorage-independent growth and differentiation
      assays to assess the effects of transgenic KrasG12D expression. KrasG12D
      overexpression transformed p53-/- myoblasts as demonstrated by an increased
      anchorage-independent growth. Induction of differentiation in parental myoblasts
      resulted in activation of key myogenic regulators. In contrast, Kras-transduced
      myoblasts had impaired terminal differentiation. p53-/- myoblasts transformed by
      KrasG12D overexpression resulted in rapid, reproducible tumor formation following
      orthotopic injection into syngeneic host hindlimbs. Pathological analysis
      revealed high-grade sarcomas with myogenic differentiation based on the
      expression of muscle-specific markers, such as Myod1 and Myog. Gene expression
      patterns of murine sarcomas shared biological pathways with RMS gene sets as
      determined by gene set enrichment analysis (GSEA) and were 61% similar to human
      RMS as determined by metagene analysis. Thus, our novel model system is an
      effective means to model high-grade sarcomas along the RMS spectrum. 

PMID- 25992773
TI  - Pit-1 inhibits BRCA1 and sensitizes human breast tumors to cisplatin and vitamin
      D treatment.
AB  - The POU class 1 homeobox 1 (POU1F1, also known as Pit-1), pertaining to the Pit
      Oct-Unc (POU) family of transcription factors, has been related to tumor growth
      and metastasis in breast. However, its role in response to breast cancer therapy
      is unknown. We found that Pit-1 down-regulated DNA-damage and repair genes, and
      specifically inhibited BRCA1 gene expression, sensitizing breast cancer cells to
      DNA-damage agents. Administration of 1alpha, 25-dihydroxy-3-epi-vitamin D3 (3
      Epi, an endogenous low calcemic vitamin D metabolite) reduced Pit-1 expression,
      and synergized with cisplatin, thus, decreasing cell proliferation and apoptosis
      in vitro, and reducing tumor growth in vivo. In addition, fifteen primary
      cultures of human breast tumors showed significantly decreased proliferation when
      treated with 3-Epi+cisplatin, compared to cisplatin alone. This response
      positively correlated with Pit-1 levels. Our findings demonstrate that high
      levels of Pit-1 and reduced BRCA1 levels increase breast cancer cell
      susceptibility to 3-Epi+cisplatin therapy.

PMID- 25992774
TI  - Use of tilapia piscidin 3 (TP3) to protect against MRSA infection in mice with
      skin injuries.
AB  - Antimicrobial peptides (AMPs), represent promising agents for new therapeutic
      approaches of infected wound treatment, on account of their antimicrobial and
      wound closure activities, and low potential for inducing resistance. However,
      therapeutic applications of these AMPs are limited by their toxicity and low
      stability in vivo. Previously, we reported that the 23 amino-acid designer
      peptide TP3 possessed antimicrobial activities. Here, we analyzed the wound
      closure activities of TP3 both and in vivo. TP3 at doses of up to 40 MUg/ml did
      not affect the viability of baby hamster kidney cells. Furthermore, TP3 was found
      to be highly effective at combating peritonitis and wound infection caused by
      MRSA in mouse models, without inducing adverse behavioral effects or liver or
      kidney toxicity. TP3 treatment increased survival by 100% at 8 days after
      infection, and accelerated the progression of proliferation, remodeling, and
      maturation of infected wounds. Taken together, our results indicate that TP3
      enhances the rate of survival of mice infected with the bacterial pathogen MRSA
      through both antimicrobial and immunomodulatory effects. Overall, these results
      suggest that TP3 may be suitable for development as a novel topical agent for
      treatment of infected wounds. 

PMID- 25992775
TI  - Self-cannulation for haemodialysis: patient attributes, clinical correlates and
      self-cannulation predilection models.
AB  - BACKGROUND AND OBJECTIVES: With emerging evidence in support of home
      haemodialysis (HHD), patient factors which determine uptake of the modality need
      to be better understood. Self-cannulation (SC) is a major step towards enabling
      self-care 'in-centre' and at home and remains the foremost barrier to its uptake.
      Human factors governing this aspect of HD practice are poorly understood. The aim
      of this study is to better understand self-cannulation preferences and factors
      which define them in end stage renal disease (ESRD). DESIGN: In this multicentre
      study, 508 of 535 patients from predialysis (Group A: n = 222), in-centre (Group
      B: n = 213), and home HD (Group C: n = 100) responded to a questionnaire with 3
      self-cannulation questions. Simultaneously, data on clinical, cognitive and
      psychosocial variables were ascertained. The primary outcome measure was
      'perceived ability to self-cannulate AV access'. Predictive models were developed
      using logistic regression analysis. RESULTS: 36.6% of predialysis patients (A)
      and 29.1% of the 'in-centre' haemodialysis patients (B) felt able to consider SC
      for HD. Technical-skills related apprehension was highest in Group B (14.4%)
      patients. Response to routine venepuncture and the types of SC concerns were
      significant predictors of perceived ability to self-cannulate. There was no
      significant difference in concern for pain across the groups. In multivariable
      regression analysis, age, education level, 3 MS score, hypoalbuminemia in Groups
      B & C and additionally, attitude to routine phlebotomy and the nature of specific
      concern for self-cannulation in Groups A, B and C, are significant predictors of
      SC preference. The unadjusted c-statistics of models 1 (derived from Group A and
      validated on A) and 2 (derived from B+C and validated on B), are 0.76(95% CI
      0.69, 0.83) and 0.80 (95% CI 0.74, 0.87) respectively. CONCLUSIONS: There is high
      prevalence of perceived ability to self-cannulate. Modifiable SC concerns exist
      in ESRD. The use of predictive models to objectively define and target education
      and training strategies could potentially impact on HD self-management and future
      uptake of home HD.

PMID- 25992776
TI  - MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer's
      Disease.
AB  - The miRBase-21 database currently lists 1881 microRNA (miRNA) precursors and 2585
      unique mature human miRNAs. Since their discovery, miRNAs have proved to present
      a new level of epigenetic post-transcriptional control of protein synthesis.
      Initial results point to a possible involvement of miRNA in Alzheimer's disease
      (AD). We applied OpenArray technology to profile the expression of 1178 unique
      miRNAs in cerebrospinal fluid (CSF) samples of AD patients (n = 22) and controls
      (n = 28). Using a Cq of 34 as cut-off, we identified positive signals for 441
      miRNAs, while 729 miRNAs could not be detected, indicating that at least 37% of
      miRNAs are present in the brain. We found 74 miRNAs being down- and 74 miRNAs
      being up-regulated in AD using a 1.5 fold change threshold. By applying the new
      explorative "Measure of relevance" method, 6 reliable and 9 informative
      biomarkers were identified. Confirmatory MANCOVA revealed reliable miR-100, miR
      146a and miR-1274a as differentially expressed in AD reaching Bonferroni
      corrected significance. MANCOVA also confirmed differential expression of
      informative miR-103, miR-375, miR-505#, miR-708, miR-4467, miR-219, miR-296, miR
      766 and miR-3622b-3p. Discrimination analysis using a combination of miR-100, miR
      103 and miR-375 was able to detect AD in CSF by positively classifying controls
      and AD cases with 96.4% and 95.5% accuracy, respectively. Referring to the
      Ingenuity database we could identify a set of AD associated genes that are
      targeted by these miRNAs. Highly predicted targets included genes involved in the
      regulation of tau and amyloid pathways in AD like MAPT, BACE1 and mTOR. 

PMID- 25992777
TI  - The use of wavelength modulated Raman spectroscopy in label-free identification
      of T lymphocyte subsets, natural killer cells and dendritic cells.
AB  - Determining the identity of cells of the immune system usually involves
      destructive fixation and chemical staining, or labeling with fluorescently
      labeled antibodies recognising specific cell surface markers. Completely label
      free identification would be a significant advantage in conditions where
      untouched cells are a priority. We demonstrate here the use of Wavelength
      Modulated Raman Spectroscopy, to achieve label-free identification of purified,
      unfixed and untouched populations of major immune cell subsets isolated from
      healthy human donors. Using this technique we have been able to distinguish
      between CD4(+) T lymphocytes, CD8(+) T lymphocytes and CD56(+) Natural Killer
      cells at specificities of up to 96%. Additionally, we have been able to
      distinguish between CD303(+) plasmacytoid and CD1c(+) myeloid dendritic cell
      subsets, the key initiator and regulatory cells of many immune responses. This
      demonstrates the ability to identify unperturbed cells of the immune system, and
      opens novel opportunities to analyse immunological systems and to develop fully
      label-free diagnostic technologies.

PMID- 25992778
TI  - Model-Free RNA Sequence and Structure Alignment Informed by SHAPE Probing Reveals
      a Conserved Alternate Secondary Structure for 16S rRNA.
AB  - Discovery and characterization of functional RNA structures remains challenging
      due to deficiencies in de novo secondary structure modeling. Here we describe a
      dynamic programming approach for model-free sequence comparison that incorporates
      high-throughput chemical probing data. Based on SHAPE probing data alone,
      ribosomal RNAs (rRNAs) from three diverse organisms--the eubacteria E. coli and
      C. difficile and the archeon H. volcanii--could be aligned with accuracies
      comparable to alignments based on actual sequence identity. When both base
      sequence identity and chemical probing reactivities were considered together,
      accuracies improved further. Derived sequence alignments and chemical probing
      data from protein-free RNAs were then used as pseudo-free energy constraints to
      model consensus secondary structures for the 16S and 23S rRNAs. There are
      critical differences between these experimentally-informed models and currently
      accepted models, including in the functionally important neck and decoding
      regions of the 16S rRNA. We infer that the 16S rRNA has evolved to undergo large
      scale changes in base pairing as part of ribosome function. As high-quality RNA
      probing data become widely available, structurally-informed sequence alignment
      will become broadly useful for de novo motif and function discovery.

PMID- 25992780
TI  - Asymmetric Total Synthesis of Bioactive Natural Lipid Mycalol.
AB  - A concise and convergent route for stereoselective total synthesis of promising
      anticancer natural lipid mycalol has been achieved using cheap and readily
      available l-arabinose as a chiral pool. The notable features of our synthesis
      comprised regioselective Wacker oxidation, Sharpless asymmetric dihydroxylation,
      Julia-Kocienski olefination, Wittig olefination, Zipper reaction, and Sonogashira
      reaction. Comparison of the spectroscopic data on a series of isomers supports
      the revised structure (Org. Lett. 2015, 17, 1652) instead of the one originally
      proposed. 

PMID- 25992779
TI  - Feasibility and Safety of Local Treatment with Recombinant Human Tissue Factor
      Pathway Inhibitor in a Rat Model of Streptococcus pneumoniae Pneumonia.
AB  - Pulmonary coagulopathy is intrinsic to pulmonary injury including pneumonia.
      Anticoagulant strategies could benefit patients with pneumonia, but systemic
      administration of anticoagulant agents may lead to suboptimal local levels and
      may cause systemic hemorrhage. We hypothesized nebulization to provide a safer
      and more effective route for local administration of anticoagulants. Therefore,
      we aimed to examine feasibility and safety of nebulization of recombinant human
      tissue factor pathway inhibitor (rh-TFPI) in a well-established rat model of
      Streptococcus (S.) pneumoniae pneumonia. Thirty minutes before and every 6 hours
      after intratracheal instillation of S. pneumonia causing pneumonia, rats were
      subjected to local treatment with rh-TFPI or placebo, and sacrificed after 42
      hours. Pneumonia was associated with local as well as systemic activation of
      coagulation. Nebulization of rh-TFPI resulted in high levels of rh-TFPI in
      bronchoalveolar lavage fluid, which was accompanied by an attenuation of
      pulmonary coagulation. Systemic rh-TFPI levels remained undetectable, and
      systemic TFPI activity and systemic coagulation were not affected. Histopathology
      revealed no bleeding in the lungs. We conclude that nebulization of rh-TFPI seems
      feasible and safe; local anticoagulant treatment with rh-TFPI attenuates
      pulmonary coagulation, while not affecting systemic coagulation in a rat model of
      S. pneumoniae pneumonia. 

PMID- 25992781
TI  - An unsupported preference for intravenous antibiotics.

PMID- 25992782
TI  - Human papillomavirus infection and fertility alteration: a systematic review.
AB  - BACKGROUND: HPV is the most prevalent sexually transmitted infection and its
      effect in cancer induction is well documented. HPV infections are mostly
      asymptomatic, but it is unclear whether HPV infections can result in alterations
      of reproductive health. OBJECTIVE: To determine the relationship between human
      papillomavirus infections and reproductive health in both men and women. METHODS:
      A systematic literature review was performed in PubMed and ScienceDirect data
      bases from January 1994 through August 2014. RESULTS: HPV infections are shown to
      be significantly associated to many adverse effects in the reproductive function.
      These adverse effects were reported in different levels from cells production to
      pregnancy and may be related to the infecting genotype. CONCLUSIONS: It appears
      from this study that HPV detection and genotyping could be of great value in
      infertility diagnosis at least in idiopathic infertility cases. Like for the risk
      of carcinogenesis, another classification of HPV regarding the risk of fertility
      alteration may be considered after deep investigations.

PMID- 25992783
TI  - A pilot study to assess effects of long-term inhalation of airborne particulate
      matter on early Alzheimer-like changes in the mouse brain.
AB  - Exposure to air pollutants, including particulate matter, results in activation
      of the brain inflammatory response and Alzheimer disease (AD)-like pathology in
      dogs and humans. However, the length of time required for inhalation of ambient
      particulate matter to influence brain inflammation and AD pathology is less
      clear. Here, we studied the effect of 3 and 9 months of air particulate matter
      (<2.5 MUm diameter, PM2.5) exposure on brain inflammatory phenotype and
      pathological hallmarks of AD in C57BL/6 mice. Using western blot, ELISA, and
      cytokine array analysis we quantified brain APP, beta-site APP cleaving enzyme
      (BACE), oligomeric protein, total Abeta 1-40 and Abeta 1-42 levels, inducible
      nitric oxide synthase (iNOS), nitrotyrosine-modified proteins, HNE-Michael
      adducts, vascular cell adhesion molecule 1 (VCAM-1), glial markers (GFAP, Iba-1),
      pre- and post- synaptic markers (synaptophysin and PSD-95), cyclooxygenase (COX
      1, COX-2) levels, and the cytokine profile in PM2.5 exposed and filtered air
      control mice. Only 9 month PM2.5 exposure increased BACE protein levels, APP
      processing, and Abeta 1-40 levels. This correlated with a concomitant increase in
      COX-1 and COX-2 protein levels and a modest alteration in the cytokine profile.
      These data support the hypothesis that prolonged exposure to airborne particulate
      matter has the potential to alter brain inflammatory phenotype and promote
      development of early AD-like pathology. 

PMID- 25992786
TI  - Effects of reverse headgear on pharyngeal airway in patients with different
      vertical craniofacial features.
AB  - The aim of this study was to investigate the effects of reverse headgear (RH) on
      pharyngeal airway morphology in two groups of Class III patients with different
      vertical craniofacial features in comparison with an untreated Class III group.
      Seventeen subjects (9 males, 8 females; mean age 11.3 +/- 0.98 years) with
      optimum vertical growth and 17 subjects (10 males, 7 females, mean age 11.5 +/-
      1.1 years) with a vertical growth pattern treated with a removable intra-oral
      appliance and a Delaire type facemask were included. An untreated Class III
      control group of 11 subjects (8 males, 3 females, mean age 9.1 +/- 1.1 years) was
      included to compare the treated groups. The paired t-test for intragroup and one
      way ANOVA for intergroup comparisons were performed. The relationships between
      changes in the craniofacial morphology and airway were assessed by Spearman
      correlation analysis. The airway dimensions at the adenoid side and soft palate
      were increased in the treatment groups compared to the control group (p < 0.05).
      The nasopharyngeal area demonstrated a significant difference in normodivergent
      and control subjects (p < 0.05). No significant difference was found in the
      airway morphology due to different vertical features. The effect of RH treatment
      on the sagittal airway dimensions revealed no significant difference between
      different vertical craniofacial features in the short term. 

PMID- 25992785
TI  - Novel heparan sulfate-binding peptides for blocking herpesvirus entry.
AB  - Human cytomegalovirus (HCMV) infection can lead to congenital hearing loss and
      mental retardation. Upon immune suppression, reactivation of latent HCMV or
      primary infection increases morbidity in cancer, transplantation, and late stage
      AIDS patients. Current treatments include nucleoside analogues, which have
      significant toxicities limiting their usefulness. In this study we screened a
      panel of synthetic heparin-binding peptides for their ability to prevent CMV
      infection in vitro. A peptide designated, p5+14 exhibited ~ 90% reduction in
      murine CMV (MCMV) infection. Because negatively charged, cell-surface heparan
      sulfate proteoglycans (HSPGs), serve as the attachment receptor during the
      adsorption phase of the CMV infection cycle, we hypothesized that p5+14
      effectively competes for CMV adsorption to the cell surface resulting in the
      reduction in infection. Positively charged Lys residues were required for peptide
      binding to cell-surface HSPGs and reducing viral infection. We show that this
      inhibition was not due to a direct neutralizing effect on the virus itself and
      that the peptide blocked adsorption of the virus. The peptide also inhibited
      infection of other herpesviruses: HCMV and herpes simplex virus 1 and 2 in vitro,
      demonstrating it has broad-spectrum antiviral activity. Therefore, this peptide
      may offer an adjunct therapy for the treatment of herpes viral infections and
      other viruses that use HSPGs for entry. 

PMID- 25992787
TI  - In vitro effectiveness of Brazilian brown propolis against Enterococcus faecalis.
AB  - The aim of this study was to evaluate the in vitro antimicrobial activity of
      Brazilian brown propolis as an intracanal medication against Enterococcus
      faecalis. Thirty dentin discs prepared from intact freshly extracted bovine
      maxillary central incisors were infected with E. faecalis for 21 days. The
      specimens were distributed into six groups according to the medicament used as
      follows: G1- calcium hydroxide paste; G2- Carbowax 400 (control group); G3- 20%
      brown propolis paste; G4- 40% brown propolis paste; G5- 20% brown propolis paste
      + calcium hydroxide paste; and G6- 40% brown propolis paste + calcium hydroxide
      paste. The experimental pastes were placed into the canal lumen and left for 14
      days. After each period, irrigation was performed with sterile saline to remove
      the medicament, and the canals were dried with sterile paper points. The dentin
      chips were removed from the canals with sequential sterile round burs at low
      speed and were immediately collected in separate test tubes containing BHI broth.
      The tubes were incubated at 37 degrees C, and microbial growth was analyzed by
      spectrophotometry after 15 days. All the experimental medications significantly
      reduced the number of viable bacteria. The G4 and G5 pastes were more effective
      than the G1 paste, with 35.8%, 41%, and 21.3% antibacterial activity,
      respectively. Brazilian brown propolis shows antibacterial capacity against E.
      faecalis. 

PMID- 25992784
TI  - A new therapeutic assessment score for advanced hepatocellular carcinoma patients
      receiving hepatic arterial infusion chemotherapy.
AB  - BACKGROUND & AIMS: Hepatic arterial infusion chemotherapy (HAIC) is an option for
      treating advanced hepatocellular carcinoma (HCC). Because of the poor prognosis
      in HAIC non-responders, it is important to identify patients who may benefit from
      continuous HAIC treatment; however, there are currently no therapeutic assessment
      scores for this identification. Therefore, we aimed to establish a new
      therapeutic assessment score for such patients. METHODS: We retrospectively
      analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP)
      and/or des-gamma-carboxy prothrombin (DCP) levels and analyzed various parameters
      for their possible use as predictors of response and survival. AFP and DCP
      responses were assessed after half a course of HAIC (2 weeks); a positive
      response was defined as a reduction of >= 20% from baseline. RESULTS:
      Multivariate analysis identified DCP response (odds ratio 16.03, p < 0.001) as an
      independent predictor of treatment response. In multivariate analysis, Child-Pugh
      class A (hazard ratio [HR] 1.99, p = 0.018), AFP response (HR 2.17, p = 0.007),
      and DCP response (HR 1.90, p = 0.030) were independent prognostic predictors. We
      developed an Assessment for Continuous Treatment with HAIC (ACTH) score,
      including the above 3 factors, which ranged from 0 to 3. Patients stratified into
      two groups according to this score showed significantly different prognoses (<= 1
      vs. >= 2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003).
      CONCLUSIONS: The ACTH score may be useful in the therapeutic assessment of HCC
      patients receiving HAIC.

PMID- 25992788
TI  - Effect of endodontic chelating solutions on the bond strength of endodontic
      sealers.
AB  - The purpose of this in vitro study was to evaluate the effect of various
      chelating solutions on the radicular push-out bond strength of calcium silicate
      based and resin-based root canal sealers. Root canals of freshly-extracted single
      rooted teeth (n = 80) were instrumented by using rotary instruments. The
      specimens were randomly divided into 4 groups according to the chelating
      solutions being tested: (1) 17% ethylenediaminetetraacetic acid (EDTA); (2) 9%
      etidronic acid; (3) 1% peracetic acid (PAA); and (4) distilled water (control).
      In each group, the roots were further assigned into 2 subgroups according to the
      sealer used: (1) an epoxy resin-based sealer (AH Plus) and (2) a calcium silicate
      based sealer (iRoot SP). Four 1 mm-thick sections were obtained from the coronal
      aspect of each root (n = 40 slices/group). Push-out bond strength test was
      performed at a crosshead speed of 1 mm/min., and the bond strength data were
      analyzed statistically with two-way analysis of variance (ANOVA) with
      Bonferroni's post hoc test (p < 0.05). Failure modes were assessed quantitatively
      under a stereomicroscope. Irrespective of the irrigation regimens, iRoot SP
      exhibited significantly higher push-out bond strength values than AH Plus (p <
      0.05). For both the sealers, the use of chelating solutions increased the bond
      strength, but to levels that were not significantly greater than their respective
      controls (p > 0.05). iRoot SP showed higher resistance to dislocation than AH
      Plus. Final irrigation with 17% EDTA, 9% Etidronic acid, and 1% PAA did not
      improve the bond strength of AH Plus and iRoot SP to radicular dentin. 

PMID- 25992789
TI  - A quantitative study of bias triangles presented in chemical potential space.
AB  - We present measurements of bias triangles in several biasing configurations.
      Using a capacitive model and two fit parameters we are able to predict the shapes
      and locations of the bias triangles in all measurement configurations.
      Furthermore, analysis of the data using this model allows us to present data from
      all four possible bias configurations on a single plot in chemical potential
      space. This presentation allows comparison between different biasing directions
      to be made in a clean and straightforward manner. Our analysis and presentation
      will prove useful in demonstrations of Pauli-spin blockade where comparisons
      between different biasing directions are paramount. The long term stability of
      the CMOS compatible Si/SiO2 only architecture leads to the success of this
      analysis. We also propose a simple variation to this analysis that will extend
      its use to systems lacking the long term stability of these devices. 

PMID- 25992790
TI  - Virtual Viewing Time: The Relationship between Presence and Sexual Interest in
      Androphilic and Gynephilic Men.
AB  - Virtual Reality (VR) has successfully been used in the research of human behavior
      for more than twenty years. The main advantage of VR is its capability to induce
      a high sense of presence. This results in emotions and behavior which are very
      close to those shown in real situations. In the context of sex research, only a
      few studies have used high-immersive VR so far. The ones that did can be found
      mostly in the field of forensic psychology. Nevertheless, the relationship
      between presence and sexual interest still remains unclear. The present study is
      the first to examine the advantages of high-immersive VR in comparison to a
      conventional standard desktop system regarding their capability to measure sexual
      interest. 25 gynephilic and 20 androphilic healthy men underwent three
      experimental conditions, which differed in their ability to induce a sense of
      presence. In each condition, participants were asked to rate ten male and ten
      female virtual human characters regarding their sexual attractiveness. Without
      their knowledge, the subjects' viewing time was assessed throughout the rating.
      Subjects were then asked to rate the sense of presence they had experienced as
      well as their perceived realism of the characters. Results suggested that
      stereoscopic viewing can significantly enhance the subjective sexual
      attractiveness of sexually relevant characters. Furthermore, in all three
      conditions participants looked significantly longer at sexually relevant virtual
      characters than at sexually non-relevant ones. The high immersion condition
      provided the best discriminant validity. From a statistical point of view,
      however, the sense of presence had no significant influence on the discriminant
      validity of the viewing time task. The study showed that high-immersive virtual
      environments enhance realism ratings as well as ratings of sexual attractiveness
      of three-dimensional human stimuli in comparison to standard desktop systems.
      Results also show that viewing time seems to be influenced neither by sexual
      attractiveness nor by realism of stimuli. This indicates how important task
      specific mechanisms of the viewing time effect are. 

PMID- 25992791
TI  - Identification of new DNA adducts of phenylnitrenium.
AB  - Phenylnitrenium ion (PhNH(+)) may bind to nucleophiles through nitrogen as well
      as through C2 or C4 carbons. However, only adducts of the former type have been
      hitherto reported after its reaction with purine nucleosides. In this study,
      reactions of N-acetoxyaniline (PhNHOAc), a precursor to PhNH(+), with 2'
      deoxyadenosine (dA), 2'-deoxyguanosine (dG), and with DNA in vitro at
      physiological conditions are described. The reaction of PhNHOAc with dA followed
      by a hydrolytic deribosylation afforded 8-phenylaminoadenine (C8-PhNHA) together
      with a smaller amount of N(6)-(4-aminophenyl)adenine (N(6)-4APA). A similar
      reaction with dG afforded 8-phenylaminoguanine (C8-PhNHG) together with traces of
      7-(4-aminophenyl)guanine (N7-4APG). The same adducts were found also in the DNA
      treated with PhNHOAc, and all of them were identified by comparison of their HPLC
      retention times and MS(2) spectra with a set of synthesized authentic adenine
      adducts at C2, C8, N7, and N(6) positions and guanine adducts at C8, N7, and N(2)
      positions. The newly identified minor adduct, N7-4APG, represents the first proof
      of arylnitrenium adduction at the N7 position of dG, which is the prominent site
      of attack by most C-electrophiles.

PMID- 25992792
TI  - Impact of the H275Y and I223V Mutations in the Neuraminidase of the 2009 Pandemic
      Influenza Virus In Vitro and Evaluating Experimental Reproducibility.
AB  - The 2009 pandemic H1N1 (H1N1pdm09) influenza virus is naturally susceptible to
      neuraminidase (NA) inhibitors, but mutations in the NA protein can cause
      oseltamivir resistance. The H275Y and I223V amino acid substitutions in the NA of
      the H1N1pdm09 influenza strain have been separately observed in patients
      exhibiting oseltamivir-resistance. Here, we apply mathematical modelling
      techniques to compare the fitness of the wild-type H1N1pdm09 strain relative to
      each of these two mutants. We find that both the H275Y and I223V mutations in the
      H1N1pdm09 background significantly lengthen the duration of the eclipse phase (by
      2.5 h and 3.6 h, respectively), consistent with these NA mutations delaying the
      release of viral progeny from newly infected cells. Cells infected by H1N1pdm09
      virus carrying the I223V mutation display a disadvantageous, shorter infectious
      lifespan (17 h shorter) than those infected with the wild-type or MUT-H275Y
      strains. In terms of compensating traits, the H275Y mutation in the H1N1pdm09
      background results in increased virus infectiousness, as we reported previously,
      whereas the I223V exhibits none, leaving it overall less fit than both its wild
      type counterpart and the MUT-H275Y strain. Using computer simulated competition
      experiments, we determine that in the presence of oseltamivir at doses even below
      standard therapy, both the MUT-H275Y and MUT-I223V dominate their wild-type
      counterpart in all aspects, and the MUT-H275Y outcompetes the MUT-I223V. The
      H275Y mutation should therefore be more commonly observed than the I223V mutation
      in circulating H1N1pdm09 strains, assuming both mutations have a similar impact
      or no significant impact on between-host transmission. We also show that
      mathematical modelling offers a relatively inexpensive and reliable means to
      quantify inter-experimental variability and assess the reproducibility of
      results. 

PMID- 25992794
TI  - Correction: Host specificity and co-speciation in avian haemosporidia in the
      Western Cape, South Africa.

PMID- 25992793
TI  - Fully automated whole-head segmentation with improved smoothness and continuity,
      with theory reviewed.
AB  - Individualized current-flow models are needed for precise targeting of brain
      structures using transcranial electrical or magnetic stimulation (TES/TMS). The
      same is true for current-source reconstruction in electroencephalography and
      magnetoencephalography (EEG/MEG). The first step in generating such models is to
      obtain an accurate segmentation of individual head anatomy, including not only
      brain but also cerebrospinal fluid (CSF), skull and soft tissues, with a field of
      view (FOV) that covers the whole head. Currently available automated segmentation
      tools only provide results for brain tissues, have a limited FOV, and do not
      guarantee continuity and smoothness of tissues, which is crucially important for
      accurate current-flow estimates. Here we present a tool that addresses these
      needs. It is based on a rigorous Bayesian inference framework that combines image
      intensity model, anatomical prior (atlas) and morphological constraints using
      Markov random fields (MRF). The method is evaluated on 20 simulated and 8 real
      head volumes acquired with magnetic resonance imaging (MRI) at 1 mm3 resolution.
      We find improved surface smoothness and continuity as compared to the
      segmentation algorithms currently implemented in Statistical Parametric Mapping
      (SPM). With this tool, accurate and morphologically correct modeling of the whole
      head anatomy for individual subjects may now be feasible on a routine basis. Code
      and data are fully integrated into SPM software tool and are made publicly
      available. In addition, a review on the MRI segmentation using atlas and the MRF
      over the last 20 years is also provided, with the general mathematical framework
      clearly derived. 

PMID- 25992795
TI  - Correlation between Central Memory T Cell Expression and Proinflammatory Cytokine
      Production with Clinical Presentation of Multibacillary Leprosy Relapse.
AB  - BACKGROUND: Despite the efficacy of multidrug therapy, surviving Mycobacterium
      leprae causes relapse in some leprosy patients, and these patients present signs
      and symptoms of disease after healing. This study focused on the cellular immune
      response in relapsed multibacillary patients but also included non-relapsed
      multibacillary cured individuals, newly diagnosed and untreated multibacillary
      patients, paucibacillary patients just before the beginning of treatment, and
      voluntary healthy individuals for comparative analysis. METHODOLOGY/PRINCIPAL
      FINDINGS: Inhibition of CD86 expression in the blood-derived monocytes and
      dendritic cells of relapsed multibacillary patients, either ex vivo or after M.
      leprae antigen stimulation was observed by flow cytometry. In addition, no
      significant changes in Interferon-gamma (IFN-g) expression were observed in 5-day
      culture supernatants of relapsed patients in response to M. leprae, neither
      before nor after treatment, as measured by ELISA. However, these patients
      demonstrated a significant increase in central memory CD4+ and CD8+ M. leprae
      specific T cells, as assessed by multiparametric flow cytometry. The increase in
      frequency of central memory T cells in relapsed patients strongly correlated with
      the bacillary index and the number of skin lesions observed in these subjects.
      Moreover, cytokine multiplex analysis demonstrated significant antigen-specific
      production of Interlukin-1beta (IL-1b), IL-6, and Tumour Necrosis Factor (TNF) in
      the relapsed group with extremely low IL-10 production, which resulted in a high
      TNF/IL-10 ratio. CONCLUSIONS/SIGNIFICANCE: Inhibition of CD86 expression may
      function to reduce effector T cell responses against the M. leprae antigen.
      Furthermore, the predominance of central memory T cells in association with the
      high TNF/IL-10 ratio and no observed IFN-g production may be related to the
      pathogenesis of relapse in multibacillary leprosy. Therefore, our findings may be
      a direct result of the clinical presentation, including a number of skin lesions
      and bacterial load, of relapsed patients. To our knowledge, this is the first
      study correlating immune response parameters with the clinical presentation of
      relapsed multibacillary patients.

PMID- 25992796
TI  - Urine Mescaline Screening With a Biochip Array Immunoassay and Quantification by
      Gas Chromatography-Mass Spectrometry.
AB  - Mescaline, the primary psychoactive chemical in peyote cactus, has been consumed
      for thousands of years in ancient religious ceremonies. The US military wanted to
      determine if mescaline intake was a problem for personnel readiness. Twenty
      thousand seventeen urine specimens negative for cannabinoids, cocaine, opiates,
      and amphetamines were tested for mescaline with the Randox Drugs of Abuse V (DOA
      V) biochip array immunoassay at the manufacturer's recommended cutoff of 6 mcg/L.
      A sensitive and specific method for mescaline quantification in urine was
      developed and fully validated. Extracted analytes were derivatized with
      pentafluoropropionic anhydride and pentafluoropropanol and quantified by gas
      chromatography-mass spectrometry (GC/MS) with electron impact ionization.
      Standard curves, using linear least squares regression with 1/x weighting, were
      linear from 1 to 250 mcg/L with coefficients of determination >0.994. Intra- and
      inter-assay imprecision was <4.4 coefficient of variation (%CV), with accuracies
      >90.4%. Mean extraction efficiencies were >92.0% across the linear range. This
      fully validated method was applied for the confirmation of urinary mescaline in
      526 presumptive-positive specimens and 198 randomly selected presumptive-negative
      specimens at the manufacturer's 6 mcg/L cutoff. No specimen confirmed positive at
      the GC/MS limit of quantification of 1 mcg/L. Results indicated that during this
      time frame, there was insufficient mescaline drug use in the military to warrant
      routine screening in the drug testing program. However, mescaline stability,
      although assessed, could have contributed to lower prevalence. We also present a
      validated GC/MS method for mescaline quantification in urine for reliable
      confirmation of suspected mescaline intake.

PMID- 25992797
TI  - Binding of the Antagonist Caffeine to the Human Adenosine Receptor hA2AR in
      Nearly Physiological Conditions.
AB  - Lipid composition may significantly affect membrane proteins function, yet its
      impact on the protein structural determinants is not well understood. Here we
      present a comparative molecular dynamics (MD) study of the human adenosine
      receptor type 2A (hA(2A)R) in complex with caffeine--a system of high neuro
      pharmacological relevance--within different membrane types. These are POPC, mixed
      POPC/POPE and cholesterol-rich membranes. 0.8-MUs MD simulations unambiguously
      show that the helical folding of the amphipathic helix 8 depends on membrane
      contents. Most importantly, the distinct cholesterol binding into the cleft
      between helix 1 and 2 stabilizes a specific caffeine-binding pose against others
      visited during the simulation. Hence, cholesterol presence (~33%-50% in synaptic
      membrane in central nervous system), often neglected in X-ray determination of
      membrane proteins, affects the population of the ligand binding poses. We
      conclude that including a correct description of neuronal membranes may be very
      important for computer-aided design of ligands targeting hA(2A)R and possibly
      other GPCRs.

PMID- 25992798
TI  - A continuum of specialists and generalists in empirical communities.
AB  - Understanding the persistence of specialists and generalists within ecological
      communities is a topical research question, with far-reaching consequences for
      the maintenance of functional diversity. Although theoretical studies indicate
      that restricted conditions may be necessary to achieve co-occurrence of
      specialists and generalists, analyses of larger empirical (and species-rich)
      communities reveal the pervasiveness of coexistence. In this paper, we analyze
      175 ecological bipartite networks of three interaction types (animal hosts
      parasite, plant-herbivore and plant-pollinator), and measure the extent to which
      these communities are composed of species with different levels of specificity in
      their biotic interactions. We find a continuum from specialism to generalism.
      Furthermore, we demonstrate that diversity tends to be greatest in networks with
      intermediate connectance, and argue this is because of physical constraints in
      the filling of networks. 

PMID- 25992800
TI  - Exploring Spatiotemporal Trends in Commercial Fishing Effort of an Abalone
      Fishing Zone: A GIS-Based Hotspot Model.
AB  - Assessing patterns of fisheries activity at a scale related to resource
      exploitation has received particular attention in recent times. However,
      acquiring data about the distribution and spatiotemporal allocation of catch and
      fishing effort in small scale benthic fisheries remains challenging. Here, we
      used GIS-based spatio-statistical models to investigate the footprint of
      commercial diving events on blacklip abalone (Haliotis rubra) stocks along the
      south-west coast of Victoria, Australia from 2008 to 2011. Using abalone catch
      data matched with GPS location we found catch per unit of fishing effort (CPUE)
      was not uniformly spatially and temporally distributed across the study area.
      Spatial autocorrelation and hotspot analysis revealed significant spatiotemporal
      clusters of CPUE (with distance thresholds of 100's of meters) among years,
      indicating the presence of CPUE hotspots focused on specific reefs. Cumulative
      hotspot maps indicated that certain reef complexes were consistently targeted
      across years but with varying intensity, however often a relatively small
      proportion of the full reef extent was targeted. Integrating CPUE with remotely
      sensed light detection and ranging (LiDAR) derived bathymetry data using
      generalized additive mixed model corroborated that fishing pressure primarily
      coincided with shallow, rugose and complex components of reef structures. This
      study demonstrates that a geospatial approach is efficient in detecting patterns
      and trends in commercial fishing effort and its association with seafloor
      characteristics. 

PMID- 25992801
TI  - Microscopic polyangiitis: Advances in diagnostic and therapeutic approaches.
AB  - Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized
      by systemic vasculitis. The disease predominantly affects small-calibre blood
      vessels and is associated with the presence of antineutrophil cytoplasmic
      autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease
      entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low
      incidence and a slight male predominance. The aetiology of MPA remains unknown.
      There is, however, increased evidence that MPA is an autoimmune disease in which
      ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the
      systemic vasculitides, indicating that multiple organs can be affected. The major
      organs involved in MPA are the kidneys and the lungs. As expected for an illness
      that affects multiple organ systems, patients with MPA can present with a myriad
      of different symptoms. Ear, nose and throat (ENT) manifestations are not
      considered to be clinical symptoms of MPA, but in the majority of populations
      described, ENT involvement was found in surprisingly high percentages. MPA is
      part of the ANCA-associated vasculitides, which are characterized by necrotizing
      vasculitis of small vessels. Diagnosis is mainly established by clinical
      manifestations, computed tomography (TC), ANCA antibody detection and renal and
      pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has
      substantially improved the prognosis. The standardized therapeutic regimen is
      based on cyclophosphamide and corticosteroids. Using this regimen, remission can
      be achieved in most of the patients. Rituximab may represent an important
      alternative to cyclophosphamide for patients who may not respond adequately to
      antimetabolite therapies. 

PMID- 25992802
TI  - Rapid Recovery of an Urban Remnant Reptile Community following Summer Wildfire.
AB  - Reptiles in urban remnants are threatened with extinction by increased fire
      frequency, habitat fragmentation caused by urban development, and competition and
      predation from exotic species. Understanding how urban reptiles respond to and
      recover from such disturbances is key to their conservation. We monitored the
      recovery of an urban reptile community for five years following a summer wildfire
      at Kings Park in Perth, Western Australia, using pitfall trapping at five burnt
      and five unburnt sites. The reptile community recovered rapidly following the
      fire. Unburnt sites initially had higher species richness and total abundance,
      but burnt sites rapidly converged, recording a similar total abundance to unburnt
      areas within two years, and a similar richness within three years. The leaf
      litter inhabiting skink Hemiergis quadrilineata was strongly associated with
      longer unburnt sites and may be responding to the loss of leaf litter following
      the fire. Six rarely-captured species were also strongly associated with unburnt
      areas and were rarely or never recorded at burnt sites, whereas two other rarely
      captured species were associated with burnt sites. We also found that one lizard
      species, Ctenotus fallens, had a smaller average body length in burnt sites
      compared to unburnt sites for four out of the five years of monitoring. Our study
      indicates that fire management that homogenises large areas of habitat through
      frequent burning may threaten some species due to their preference for longer
      unburnt habitat. Careful management of fire may be needed to maximise habitat
      suitability within the urban landscape. 

PMID- 25992803
TI  - Thermodynamic aspects of aurophilic hydrogelators.
AB  - The complexes [Au(4-pyridylethynyl)(phosph)] (phosph = PTA (1), DAPTA (2)) are
      known to produce supramolecular aggregates and gels in water. We studied the
      impact of these aggregation processes in the absorption spectra, (1)H NMR (at
      different temperatures and concentrations), and DLS and estimated the equilibrium
      constant for a single step aggregation of the molecule (K = 26760 and 2590 M(-1)
      for 1 and 2, respectively, at 25  degrees C). We present spectroscopic evidence
      for the presence of Au...Au contacts in the aggregates: the recorded changes on
      (1)H NMR and the appearance of new absorption bands assigned to (sigma*Au...Au
      pi*) have been attributed to the short (Au...Au) average distances in the
      aggregates. Relativistic density functional theory computations support the
      existence of short Au...Au distances and reveal charge-transfer in the aurophilic
      interactions. The free energy for a single step aggregation was calculated from
      the experimental data, and the value obtained (DeltaG ~ -20 kJ/mol) is in good
      agreement with the expected values in the order of the energies found for
      hydrogen bonds. The DFT computations confirm the experimental findings that
      aggregation of monomer 1 is stronger than the aggregation of monomer 2 and the
      existence of aurophilic interactions. 

PMID- 25992804
TI  - Self-Contained Photoacid Generator Triggered by Photocyclization of Triangle
      Terarylene Backbone.
AB  - We herein propose a new type of efficient neutral photoacid generator. A
      photoinduced 6pi-electrocyclization reaction of photochromic triangle terarylenes
      triggers subsequent release of a Bronsted acid, which took place from the
      photocyclized form. A H-atom and its conjugate base were introduced at both sides
      of a 6pi-system to form the self-contained photoacid generator. UV irradiation to
      the 6pi-system produces a cyclohexa-1,3-diene part with a H-atom and a conjugate
      base on the sp(3) C-atoms at 5- and 6-positions, respectively, which
      spontaneously release an acid molecule quantitatively forming a polyaromatic
      compound. A net quantum yield of photoacid generation as high as 0.52 under
      ambient conditions and a photoinitiated cationic polymerization of an epoxy
      monomer are demonstrated. 

PMID- 25992805
TI  - Self-determined behavior change: The need for capacity, opportunity and support.
AB  - OBJECTIVE: This article discusses how self-determination is central to positive
      behavior support, provides recommendations on how to promote it, and identifies
      future areas of research. BACKGROUND: The value of incorporating self
      determination strategies in positive behavior support plans is receiving
      increased attention. Rather than continue to rely on an externally controlled
      behavior change model in which "others" (e.g., teachers, service providers)
      determine the method to use to modify the behavior of a service recipient
      (student, client), self-determination shifts the responsibility over to that
      person; that is, he or she is integrally involved in selecting an appropriate
      strategy, executing it and monitoring how well he or she is doing. CONCLUSION:
      The inclusion of self-determination strategies in positive behavior support
      warrants further attention as individuals who have challenging behavior may be in
      an optimal position to manipulate their own behavior change.

PMID- 25992806
TI  - Surgical anatomy and variations of the infraorbital nerve.
AB  - OBJECTIVES/HYPOTHESIS: To assess relevant variations in the anatomical course of
      the infraorbital nerve (ION). This understanding may reduce the risk of surgical
      injury. METHODS: A total of 100 consecutive computed-tomography sinus studies
      obtained in a tertiary referral center were reviewed, and measurements were made
      of the 200 IONs. Anatomic variants were classified into three types based on the
      degree to which (if any) the nerve's course descended from the maxillary roof
      into the sinus lumen. RESULTS: A total of 60.5% of IONs were entirely contained
      within the sinus roof. In 27.0%, the nerve canal descended below the roof but
      remained juxtaposed to it. In 12.5%, the ION descended into the sinus lumen. The
      proportion of IONs descending into the sinus significantly increased to 27.7%
      when an infraorbital ethmoid cell was present (chi-square P < 0.001) and to 50%
      when the nerve was contained within a lamella of such a cell (chi-square P <
      0.001). Descended nerves terminated in a foramen located an average of 11.9 +/-
      2.5 mm below the infraorbital rim, significantly further below the orbit than
      nondescended nerves (t test P < 0.001). Descended nerves were located a mean
      distance of 8.6 +/- 2.9 mm below the sinus roof and traversed the sinus lumen
      diagonally for a mean length of 15.4 +/- 3.1 mm. CONCLUSIONS: Descent of the ION
      into the maxillary sinus is a common anatomic variant that is more prevalent in
      the setting of an ipsilateral infraorbital ethmoid cell. Descended nerves are
      associated with the foramen significantly further below the inferior orbital rim
      than those of nondescended nerves. These observations may help surgeons avoid
      iatrogenic ION injury. LEVEL OF EVIDENCE: N/A.

PMID- 25992807
TI  - Venous thromboembolism as initial manifestation of adult onset Still's disease.

PMID- 25992808
TI  - Capturing conformational States in proteins using sparse paramagnetic NMR data.
AB  - Capturing conformational changes in proteins or protein-protein complexes is a
      challenge for both experimentalists and computational biologists. Solution
      nuclear magnetic resonance (NMR) is unique in that it permits structural studies
      of proteins under greatly varying conditions, and thus allows us to monitor
      induced structural changes. Paramagnetic effects are increasingly used to study
      protein structures as they give ready access to rich structural information of
      orientation and long-range distance restraints from the NMR signals of backbone
      amides, and reliable methods have become available to tag proteins with
      paramagnetic metal ions site-specifically and at multiple sites. In this study,
      we show how sparse pseudocontact shift (PCS) data can be used to computationally
      model conformational states in a protein system, by first identifying core
      structural elements that are not affected by the environmental change, and then
      computationally completing the remaining structure based on experimental
      restraints from PCS. The approach is demonstrated on a 27 kDa two-domain NS2B-NS3
      protease system of the dengue virus serotype 2, for which distinct closed and
      open conformational states have been observed in crystal structures. By changing
      the input PCS data, the observed conformational states in the dengue virus
      protease are reproduced without modifying the computational procedure. This data
      driven Rosetta protocol enables identification of conformational states of a
      protein system, which are otherwise difficult to obtain either experimentally or
      computationally. 

PMID- 25992809
TI  - Simultaneous ex vivo functional testing of two retinas by in vivo
      electroretinogram system.
AB  - An In vivo electroretinogram (ERG) signal is composed of several overlapping
      components originating from different retinal cell types, as well as noise from
      extra-retinal sources. Ex vivo ERG provides an efficient method to dissect the
      function of retinal cells directly from an intact isolated retina of animals or
      donor eyes. In addition, ex vivo ERG can be used to test the efficacy and safety
      of potential therapeutic agents on retina tissue from animals or humans. We show
      here how commercially available in vivo ERG systems can be used to conduct ex
      vivo ERG recordings from isolated mouse retinas. We combine the light
      stimulation, electronic and heating units of a standard in vivo system with
      custom-designed specimen holder, gravity-controlled perfusion system and
      electromagnetic noise shielding to record low-noise ex vivo ERG signals
      simultaneously from two retinas with the acquisition software included in
      commercial in vivo systems. Further, we demonstrate how to use this method in
      combination with pharmacological treatments that remove specific ERG components
      in order to dissect the function of certain retinal cell types. 

PMID- 25992811
TI  - Correction: Functional Characterization of the spf/ash Splicing Variation in OTC
      Deficiency of Mice and Man.

PMID- 25992810
TI  - SLCO1B1 polymorphism is not associated with risk of statin-induced
      myalgia/myopathy in a Czech population.
AB  - BACKGROUND: Gene SLCO1B1, encoding solute organic anionic transport polypeptide
      OATP1B1, belongs to the group of candidates potentially influencing statin
      treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its
      genetic variation was described as an important predictor of statin-associated
      myopathy in a cohort of patients treated with a maximum dose of simvastatin.
      However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated
      with other statins or lower doses of simvastatin needs to be assessed. Therefore,
      we performed the present study. MATERIAL/METHODS: SLCO1B1 tagging rs4363657
      polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with
      simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced
      myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301
      population controls without lipid-lowering treatment. RESULTS: Frequency of the
      individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%,
      CC=2.8%) did not significantly differ (both P values over 0.19) from that in
      patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the
      population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also
      obtained for the dominant and recessive models of the analysis. CONCLUSIONS: In
      Czech patients treated with low statin doses, there is no association between
      SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

PMID- 25992812
TI  - Randomized Trial of Small-diameter Versus Large-diameter Esophageal Stents for
      Palliation of Malignant Esophageal Obstruction.
AB  - GOALS: To assess the effect of esophageal stent diameter on outcomes of patients
      with malignant esophageal obstruction. BACKGROUND: Esophageal self-expandable
      metal stents (SEMS) effectively palliate dysphagia due to malignancy, but the
      best stent diameter is unknown. STUDY: A prospective randomized trial was
      conducted at a regional referral hospital. One hundred persons with unresectable
      esophageal cancer were enrolled, randomized to receive a SEMS of either 18 or 23
      mm shaft diameter but identical design, and followed until death. Outcome
      measurements were dysphagia score, adverse events, endoscopic reintervention, and
      survival. RESULTS: The study arms were evenly matched. Dysphagia resolved after
      stent placement in 95% in both groups. After 6 months the cumulative incidence of
      recurrent dysphagia was 38% (95% CI 18%-53%) versus 47% (26%-63%) in the small
      diameter versus large-diameter groups, respectively (P=0.23). The cumulative
      incidence of adverse events was 57% in both groups at 6 months, with trends
      toward more frequent gastrointestinal bleeding and esophago-respiratory fistula
      in the large-diameter group, and more frequent stent migration, stent occlusion,
      and endoscopic reintervention in the small-diameter group. There was a trend
      toward longer survival in the small-diameter group (median survival, 5.9 vs. 3
      mo; P=0.10). Higher initial performance status score and female gender were
      associated with improved survival. Limitations include enrollment of only 100 (of
      a planned 200) persons and incomplete follow-up of some participants.
      CONCLUSIONS: Small-diameter and large-diameter esophageal SEMS provided similar
      palliation of dysphagia due to esophageal cancer. The overall incidence of
      adverse events was not affected by stent diameter, but there was a trend toward
      longer survival with small-diameter stents (Clinical trial registration number:
      NCT01894763).

PMID- 25992813
TI  - Gastrointestinal Manifestations, Malnutrition, and Role of Enteral and Parenteral
      Nutrition in Patients With Scleroderma.
AB  - Scleroderma (systemic sclerosis) is an autoimmune disease that can affect
      multiple organ systems. Gastrointestinal (GI) involvement is the most common
      organ system involved in scleroderma. Complications of GI involvement including
      gastroesophageal reflux disease, small intestinal bacterial overgrowth, and
      chronic intestinal pseudoobstruction secondary to extensive fibrosis may lead to
      nutritional deficiencies in these patients. Here, we discuss pathophysiology,
      progression of GI manifestations, and malnutrition secondary to scleroderma, and
      the use of enteral and parenteral nutrition to reverse severe nutritional
      deficiencies. Increased mortality in patients with concurrent malnutrition in
      systemic sclerosis, as well as the refractory nature of this malnutrition to
      pharmacologic therapies compels clinicians to provide novel and more invasive
      interventions in reversing these nutritional deficiencies. Enteral and parenteral
      nutrition have important implications for patients who are severely malnourished
      or have compromised GI function as they are relatively safe and have substantial
      retrospective evidence of success. Increased awareness of these therapeutic
      options is important when treating scleroderma-associated malnutrition. 

PMID- 25992815
TI  - Conferences conveying the Solvay spirit in emerging scientific fields: a
      remarkable boost to knowledge building (or: Do you know what Physics said to
      Nursing Science?).

PMID- 25992814
TI  - Detection of Plasma Protease Activity Using Microsphere-Cytometry Assays with E.
      coli Derived Substrates: VWF Proteolysis by ADAMTS13.
AB  - Protease levels in human blood are often prognostic indicators of inflammatory,
      thrombotic or oncogenic disorders. The measurement of such enzyme activities in
      substrate-based assays is complicated due to the low prevalence of these enzymes
      and steric hindrance of the substrates by the more abundant blood proteins. To
      address these limitations, we developed a molecular construct that is suitable
      for microsphere-cytometer based assays in the milieu of human blood plasma. In
      this proof of principle study, we demonstrate the utility of this substrate to
      measure metalloprotease ADAMTS13 activity. The substrate, expressed in E. coli as
      a fusion protein, contains the partial A2-domain of von Willebrand factor (VWF
      amino acids 1594-1670) that is mutated to include a single primary amine at the N
      terminus and free cysteines at the C-terminus. N-terminus fluorescence
      conjugation was possible using NHS (N-hydroxysuccinimide) chemistry. Maleimide
      PEG(Polyethylene glycol)n-biotin coupling at the C-terminus allowed biotinylation
      with variable PEG spacer lengths. Once bound to streptavidin-bearing
      microspheres, the substrate fluorescence signal decreased in proportion with
      ADAMTS13 concentration. Whereas recombinant ADAMTS13 activity could be quantified
      using substrates with all PEG repeat-lengths, only the construct with the longer
      77 PEG-unit could quantify proteolysis in blood plasma. Using this longer
      substrate, plasma ADAMTS13 down to 5% of normal levels could be detected within
      30 min. Such measurements could also be readily performed under conditions
      resembling hyperbilirubinemia. Enzyme catalytic activity was tuned by varying
      buffer calcium, with lower divalent ion concentrations enhancing cleavage.
      Overall, the study highlights the substrate design features important for the
      creation of efficient proteolysis assays in the setting of human plasma. In
      particular, it emphasizes the need to introduce PEG spacers in plasma-based
      experiments, a design attribute commonly ignored in immobilized peptide-substrate
      assays. 

PMID- 25992816
TI  - [The (un)receptive experiences of female rape victims who seek healthcare
      services].
AB  - OBJECTIVE: To know the structure and functioning of healthcare services from the
      perspective of women who have suffered rape. METHOD: A qualitative study
      conducted with 11 women who experienced rape, monitored in a maternity in the
      state of Alagoas, Brazil. Data were systematically based on content analysis.
      RESULTS: It allowed for understanding the path taken by women in search of
      support from health services, as well as the limitations and capabilities of
      these services. CONCLUSION : The assistance received in healthcare services leans
      towards a revictimization process of women who already carry trauma from the
      rape. It is necessary to reflect about care practices aimed at sexually
      victimized women.

PMID- 25992817
TI  - [Arterial hypertension and associated factors in patients submitted to myocardial
      revascularization].
AB  - OBJECTIVE To identify the prevalence of arterial hypertension and associated
      factors in patients submitted to myocardial revascularization. METHOD Cross
      sectional study using the database of a hospital in Sao Paulo (SP, Brazil)
      containing 3010 patients with coronary artery disease submitted to myocardial
      revascularization. A multiple logistic regression was performed to identify
      variables independently associated with hypertension (statistical significance:
      p<0.05). RESULTS Prevalence of hypertension was 82.8%. After the variables were
      adjusted, the associated factors were as follows: age, odds ratio (OR): OR=1.01;
      95% confidence interval (CI): CI:1.00-1.02; female gender: (OR=1.77;CI:1.39
      2.25); brown-skin race: (OR=1.53;CI:1.07-2.19); obesity: (OR=1.53;CI:1.13-2.06);
      diabetes: (OR=1.90;CI:1.52-2.39); dyslipidemia: (OR=1.51;CI:1.23-1.85); and
      creatinine>1.3: (OR=1.37;CI:1.09-1.72). CONCLUSION A high prevalence of arterial
      hypertension and association with both non-modifiable and modifiable factors was
      observed. 

PMID- 25992818
TI  - [Terms of international classification for Nursing Practice in motor and physical
      rehabilitation].
AB  - OBJECTIVE: To validate terms of nursing language especially for physical-motor
      rehabilitation and map them to the terms of ICNP((r)) 2.0. METHOD: A methodology
      research based on document analysis, with collection and analysis of terms from
      1,425 records. RESULTS: 825 terms were obtained after the methodological
      procedure, of which 226 had still not been included in the ICNP((r)) 2.0. These
      terms were distributed as follows: 47 on the Focus axis; 15 on the Judgment axis;
      31 on the Action axis; 25 on the Location axis; 102 on the Means axis; three on
      the Time axis; and three on the Client axis. All non-constant terms in ICNP((r))
      have been validated by experts, having reached an agreement index >=0.80.
      CONCLUSION: The ICNP((r)) is applicable and used in nursing care for physical
      motor rehabilitation.

PMID- 25992819
TI  - [Antimicrobial activity of Eucalyptus globulus oil, xylitol and papain: a pilot
      study].
AB  - OBJECTIVE: To evaluate the in vitro antimicrobial activity of the Eucalyptus
      globulus essential oil, and of the xylitol and papain substances against the
      following microorganisms: Pseudomonas aeruginosa; Samonella sp.; Staphylococus
      aureus; Proteus vulgaris; Escherichia coli and Candida albicans. METHOD: The in
      vitro antimicrobial evaluation was used by means of the agar diffusion test and
      evaluation of the inhibition zone diameter of the tested substances.
      Chlorhexidine 0.5% was used as control. RESULTS: The Eucalyptus globulus oil
      showed higher inhibition than chlorhexidine when applied to Staphylococcus
      aureus, and equal inhibition when applied to the following microorganisms:
      Escherichia coli, Proteus vulgaris and Candida albicans. Papain 10% showed lower
      antimicrobial effect than chlorhexidine in relation to Candida albicans. Xylitol
      showed no inhibition of the tested microorganisms. CONCLUSION: The Eucalyptus
      globulus oil has antimicrobial activity against different microorganisms and
      appears to be a viable alternative as germicidal agent hence, further
      investigation is recommended.

PMID- 25992820
TI  - [Usage of Calendula officinalis in the prevention and treatment of
      radiodermatitis: a randomized double-blind controlled clinical trial].
AB  - OBJECTIVE: To evaluate the efficacy of Calendula officinalis in relation to
      Essential Fatty Acids for the prevention and treatment of radiodermatitis.
      METHOD: This is a randomized double-blind controlled clinical trial with 51
      patients with head and neck cancer in radiotherapy treatment divided into two
      groups: control (27) and experimental (24). RESULTS: There is statistically
      significant evidence (p-value = 0.0120) that the proportion of radiodermatitis
      grade 2 in Essential Fatty Acids group is higher than Calendula group. Through
      the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has
      always remained below the Calendula group survival curve, due to the lower risk
      of developing radiodermatitis grade 1, which makes the usage of Calendula more
      effective, with statistical significance (p-value = 0.00402). CONCLUSION:
      Calendula showed better therapeutic response than the Essential Fatty Acids in
      the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical
      Trials: RBR-237v4b.

PMID- 25992821
TI  - [Late diagnosis and vulnerabilities of the elderly living with HIV/AIDS].
AB  - OBJECTIVE: To identify vulnerabilities of elderly people with HIV/AIDS and the
      trajectory that they follow until reaching the diagnosis of the disease. METHOD:
      Qualitative research conducted in specialized clinics in the state of Sao Paulo,
      from January to June 2011. Semi-structured interviews were conducted with 11
      elderly people who were found to be infected with the virus at the age of 60
      years or older. The interviews were analyzed using content analysis. RESULTS: In
      this process four categories emerged, then analyzed with reference to the
      theoretical framework of vulnerability. CONCLUSION: Late diagnosis of HIV
      infection or AIDS among the elderly happens in the secondary or tertiary service.
      Issues related to sexual life of the elderly are only questioned by health
      professionals after the diagnosis, also the time that condom use becomes
      absolute. It is believed that the investigation of the vulnerability of the
      elderly to HIV/AIDS allows for carrying out appropriate interventions for this
      population.

PMID- 25992822
TI  - [Development of the short version of the informal caregiver burden assessment
      questionnaire].
AB  - OBJETIVE: to create a reduced version of the QASCI, which is structurally
      equivalent to the long one and meets the criteria of reliability and validity.
      METHOD: Through secondary data from previous studies, the participants were
      divided into two samples, one for the development of reduced version and the
      second for study of the factorial validity. Participants responded to QASCI, the
      SF 36, the ADHS and demographic questions. RESULTS: A reduced version of 14 items
      showed adequate psychometric properties of validity and internal consistency,
      adapted to a heptadimensional structure that assesses positive and negative
      aspects of care. CONCLUSION: Confirmatory factor analysis revealed a good fit
      with the advocated theoretical model.

PMID- 25992823
TI  - [Quality of life of caregivers for patients of cerebrovascular accidents:
      association of (socio-demographic) characteristics and burden].
AB  - OBJECTIVE: Investigating the association between quality of life with socio
      demographic characteristics and the burden of caregivers for individuals with
      cerebrovascular accident sequelae. METHOD: A descriptive, cross-sectional study
      with a sample composed of 136 caregivers. For data collection, a semi-structured
      questionnaire, the Barthel, Burden Interview and Short-Form-36 scales were used.
      Correlation analysis, t-Student test and F-test were used for the analysis in
      order to compare averages. RESULTS: Significant averages in quality of life were
      demonstrated in association with female caregivers and those over 60 years in the
      field 'functional capacity,' and in the domains of 'mental health' and 'vitality'
      for those with higher income. Regarding burden association, the highlighted areas
      were 'functional capacity,' 'physical aspects,' 'emotional aspects' and 'pain.'
      CONCLUSION: The creation of public policies and social support to effectively
      reduce the burden on caregivers is a necessity.

PMID- 25992824
TI  - [Prevalence of burnout syndrome in health professionals of an onco-hematological
      pediatric hospital].
AB  - OBJECTIVE: To identify the prevalence of Burnout Syndrome in medical
      professionals, nurses and nursing technicians working in an Onco-Hematological
      Pediatric Hospital in Sao Paulo. METHOD: An exploratory, descriptive study with
      cross-sectional design and quantitative approach, with a sample of 188 health
      professionals. Data were collected using two self-report instruments: the Maslach
      Burnout Inventory (MBI-HSS) which is a biosocial data form, and a non-participant
      observation guide. RESULTS: High depersonalization for nurses (29.8%), low job
      performance for physicians (27.8%), and of nursing technicians (25.5%). High
      scores were identified in at least two domains of Burnout in 19.2% of nurses,
      16.8% of nursing technicians, and 16.6% of doctors. CONCLUSION: Health
      professionals are highly vulnerable to each of the dimensions of Burnout syndrome
      - namely emotional exhaustion, alienation, and low job performance/satisfaction-
      in the hospital work.

PMID- 25992825
TI  - [Clinical treatment adherence of health care workers and students exposed to
      potentially infectious biological material].
AB  - OBJECTIVE: To assess adherence to clinical appointments by health care workers
      (HCW) and students who suffered accidents with potentially infectious biological
      material. METHOD: A retrospective cross-sectional study that assessed clinical
      records of accidents involving biological material between 2005 and 2010 in a
      specialized unit. RESULTS: A total of 461 individuals exposed to biological
      material were treated, of which 389 (84.4%) were HCWs and 72 (15.6%) students. Of
      the 461 exposed individuals, 307 (66.6%) attended a follow-up appointment.
      Individuals who had suffered an accident with a known source patient were 29
      times more likely to show up to their scheduled follow-up appointments (OR:
      29.98; CI95%: 16.09-55.83). CONCLUSION: The predictor in both univariate and
      multivariate analyses for adherence to clinical follow-up appointment was having
      a known source patient with nonreactive serology for the human immunodeficiency
      virus and/or hepatitis B and C.

PMID- 25992826
TI  - [Scientific production on workplace bullying/harassment in dissertations and
      theses in the Brazilian scenario].
AB  - OBJECTIVE To analyze scientific production about workplace bullying and
      harassment in dissertations and theses in Brazil, with emphasis on the year of
      publication; educational institution; area of knowledge; professional and
      academic background of the authors; keywords used; and concept map organization.
      METHOD Bibliometric study with a quantitative approach with a sample consisting
      of 57 papers, 5 theses and 52 dissertations, published between 2002 and 2012.
      RESULTS It was found that 2012 was the year with the highest number of
      publications in this topic area. The region that stood out was the Southeast. The
      institution with the highest number of publications was the Federal University of
      Santa Catarina. There was a predominance of dissertations and most publications
      were produced by researchers focused on a multidisciplinary perspective.
      CONCLUSION Expanding the views regarding bullying in order to disseminate
      scientific production was proposed, promoting further advancement of debates and
      raising pertinent questions. 

PMID- 25992827
TI  - [Patient safety management from the perspective of nurses].
AB  - OBJECTIVE: To evaluate the actions of patient safety management developed in
      hospitals, from the perspective of nurses. METHOD: This is a cross-sectional,
      descriptive study of the survey type. Participants were seven hospitals, in which
      seven nurse managers and 49 sector coordinator nurses (n = 56) answered the
      instrument prepared by the author. RESULTS: The results showed that 100% of
      hospitals have an adverse event reporting system, 71.4% have a Risk Management
      Committee and 80% have discussions about the events. There is agreement that
      these discussions lead to favorable changes for patient safety in the surveyed
      institutions. The employees' fear of punishment for their faults, and the
      underreporting of events were the aspects of greatest weakness found. CONCLUSION:
      The institutions should develop organizational policies focused on stimulating
      event notification and on the implementation of measures directed to a non
      punitive organizational culture.

PMID- 25992828
TI  - [Educational group practices in primary care: interaction between professionals,
      users and knowledge].
AB  - OBJECTIVE: To investigate the concept understood by Family Healthcare Strategy
      (ESF) professionals of knowledge, education and subjects participating in
      learning activities. METHOD: Qualitative study carried out with the ESF
      professionals with university degree, members of the healthcare staff who
      undertook educational health group activities at Basic Healthcare Units (UBS) in
      Belo Horizonte. The following triangulation techniques were used: participant
      observation, photos and field notes; interviews with professionals; and document
      analysis. RESULTS: We identified three interaction patterns that are different
      from each other. Firstly, the professional questions, listens and provides
      information to users, trusting in the transmission of knowledge; secondly, the
      professional questions and listens, trusting that users can learn from each
      other; thirdly, the professional questions, listens, discusses and produces
      knowledge with users, both teaching and learning from each other. CONCLUSION:
      There are educational practices that include unique methods capable of creating a
      militant space for citizenship engagement.

PMID- 25992829
TI  - [Educational intervention on malignant hyperthermia with nursing professionals of
      the operating room].
AB  - OBJECTIVE: To evaluate the effectiveness of an educational intervention on
      malignant hyperthermia with operating room nurses. METHOD: A quasi-experimental
      study, aimed at an educational intervention of short duration with the nursing
      staff in the operating room of the institution hosting the research in the city
      of Sao Paulo, with the participation of 96 professionals. Pre-intervention tests
      and post-intervention tests were applied, which consisted of a lecture followed
      by simulation. RESULTS: Considering the overall results of the intervention,
      there was a statistically significant difference (p<0.00). After the educational
      intervention, there was an increase of the minimum and maximum scores, and
      average growth of 2.64 points in the knowledge of professionals when compared to
      the previous step. CONCLUSION: The educational intervention strategy favors the
      concept of the content developed by everyone involved and qualifies professionals
      to work safely.

PMID- 25992830
TI  - [Evaluation of professional knowledge and attitudes on dementia patient care: a
      trans-cultural adaptation of an evaluation instrument].
AB  - OBJECTIVE: To describe the trans-cultural adaptation of the evaluation instrument
      entitled Atencio Sanitaria de Les Demencies: la visio de L' Atencio Primaria from
      Catalan into versions in Portuguese for doctors and nurses. This study evaluates
      the knowledge and perspectives of these professionals in their treatment of
      patients diagnosed with dementia in cases of primary care. METHOD: The adaptation
      followed internationally accepted rules, which include the following steps:
      translation, synthesis, back-translation, revision by a committee of specialists,
      and a test run with 35 practicing doctors and 35 practicing nurses in Brazil's
      Family Health Strategy (Estrategia Saude da Familia, or ESF in Portuguese).
      RESULTS: The translation, synthesis, and back-translation steps were performed
      satisfactorily; only small adjustments were required. The committee of
      specialists verified the face validity in the version translated into Portuguese,
      and all of the items that received an agreement score lower than 80% during the
      initial evaluation were revised. In the test run, the difficulties presented by
      the health care professionals did not reach 15% of the sample, and therefore, no
      changes were made. CONCLUSION: The Portuguese translation of the instrument can
      be considered semantically, idiomatically, culturally, and conceptually
      equivalent to the original Catalan version and is, therefore, appropriate for use
      in Brazil.

PMID- 25992831
TI  - [Mediate evaluation of replicating a Training Program in Nonverbal Communication
      in Gerontology].
AB  - OBJECTIVE: Replicating the training program in non-verbal communication based on
      the theoretical framework of interpersonal communication; non-verbal coding,
      valuing the aging aspects in the perspective of active aging, checking its
      current relevance through the content assimilation index after 90 days (mediate)
      of its application. METHOD: A descriptive and exploratory field study was
      conducted in three hospitals under direct administration of the state of Sao
      Paulo that caters exclusively to Unified Health System (SUS) patients. The
      training lasted 12 hours divided in three meetings, applied to 102 health
      professionals. RESULTS: Revealed very satisfactory and satisfactory mediate
      content assimilation index in 82.9%. CONCLUSION: The program replication proved
      to be relevant and updated the setting of hospital services, while remaining
      efficient for healthcare professionals.

PMID- 25992832
TI  - [Instrument for evaluating care given by undergraduate nursing students to people
      with wounds].
AB  - OBJECTIVE: The aim of this study was to present the process of construction and
      validation of an instrument for evaluating the care provided to people with
      wounds, to be used with undergraduate nursing students. METHOD :Methodological
      study, with quantitative approach, using the Delphi technique in two rounds, the
      first with 30 judges and the second with 18. The analysis was made with Kappa
      coefficient >=0.80, and content validity index greater than >0.80, also using the
      Wilcoxon test for comparison of the indices between the rounds. RESULTS: It was
      found that of the 20 categories of the instrument, 18 presented better scores in
      the second Delphi round. Scores were greater in the second round in seven of the
      ten evaluation categories. CONCLUSION: Based on the evaluation by the judges, a
      version of the instrument was defined with adequate indices of agreement and
      validity, which will be able to help in evaluating care of people with cutaneous
      injury given by undergraduate nursing students.

PMID- 25992833
TI  - [Usability of computerized nursing process from the ICNP(r) in intensive care
      units].
AB  - OBJECTIVE: To analyze the usability of Computerized Nursing Process (CNP) from
      the ICNP((r)) 1.0 in Intensive Care Units in accordance with the criteria
      established by the standards of the International Organization for
      Standardization and the Brazilian Association of Technical Standards of systems.
      METHOD: This is a before-and-after semi-experimental quantitative study, with a
      sample of 34 participants (nurses, professors and systems programmers), carried
      out in three Intensive Care Units. RESULTS: The evaluated criteria (use, content
      and interface) showed that CNP has usability criteria, as it integrates a logical
      data structure, clinical assessment, diagnostics and nursing interventions.
      CONCLUSION: The CNP is a source of information and knowledge that provide nurses
      with new ways of learning in intensive care, for it is a place that provides
      complete, comprehensive, and detailed content, supported by current and relevant
      data and scientific research information for Nursing practices.

PMID- 25992834
TI  - [Chemotherapy-induced peripheral neuropathies: an integrative review of the
      literature].
AB  - OBJECTIVE: To identify scientific studies and to deepen the knowledge of
      peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence
      for assistance to cancer patients. METHOD: Integrative review of the literature
      conducted in the databases Latin American and Caribbean Health Sciences (LILACS),
      Scientific Electronic Library Online (SciELO), Medical Literature Analysis
      (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health
      Sciences (IBECS). RESULTS: The sample consisted of 15 studies published between
      2005-2014 that met the inclusion criteria. Studies showed aspects related to
      advanced age, main symptoms of neuropathy and chemotherapy agents as important
      adverse effect of neuropathy. CONCLUSION: We identified a small number of studies
      that addressed the topic, as well as low production of evidence related to
      interventions with positive results. It is considered important to develop new
      studies proposed for the prevention and/or treatment, enabling adjustment of the
      patient's cancer chemotherapy and consequently better service.

PMID- 25992835
TI  - Consensus on the development of vaccines against naturally acquired melioidosis.
AB  - Several candidates for a vaccine against Burkholderia pseudomallei, the causal
      bacterium of melioidosis, have been developed, and a rational approach is now
      needed to select and advance candidates for testing in relevant nonhuman primate
      models and in human clinical trials. Development of such a vaccine was the topic
      of a meeting in the United Kingdom in March 2014 attended by international
      candidate vaccine developers, researchers, and government health officials. The
      focus of the meeting was advancement of vaccines for prevention of natural
      infection, rather than for protection from the organism's known potential for use
      as a biological weapon. A direct comparison of candidate vaccines in well
      characterized mouse models was proposed. Knowledge gaps requiring further
      research were identified. Recommendations were made to accelerate the development
      of an effective vaccine against melioidosis. 

PMID- 25992836
TI  - The alternate role of direct and environmental transmission in fungal infectious
      disease in wildlife: threats for biodiversity conservation.
AB  - Emerging fungal pathogens have substantial consequences for infected hosts, as
      revealed by the global decline of amphibian species from the chytrid fungus.
      According to the "curse of the Pharaoh" hypothesis, free-living infectious stages
      typical of fungal pathogens lengthen the timespan of transmission. Free-living
      infectious stages whose lifespan exceeds the infection time of their hosts are
      not constrained by virulence, enabling them to persist at high levels and
      continue transmitting to further sensitive hosts. Using the only Mesomycetozoea
      fungal species that can be cultured, Sphaerothecum destruens, we obtained
      tractable data on infectivity and pathogen life cycle for the first time. Here,
      based on the outcomes of a set of infectious trials and combined with an
      epidemiological model, we show a high level of dependence on direct transmission
      in crowded, confined environments and establish that incubation rate and length
      of infection dictate the epidemic dynamics of fungal disease. The spread of
      Mesomycetozoea in the wild raise ecological concerns for a range of susceptible
      species including birds, amphibians and mammals. Our results shed light on the
      risks associated with farming conditions and highlight the additional risk posed
      by invasive species that are highly abundant and can act as infectious reservoir
      hosts. 

PMID- 25992837
TI  - Spatiotemporal patterns and predictability of cyberattacks.
AB  - A relatively unexplored issue in cybersecurity science and engineering is whether
      there exist intrinsic patterns of cyberattacks. Conventional wisdom favors
      absence of such patterns due to the overwhelming complexity of the modern
      cyberspace. Surprisingly, through a detailed analysis of an extensive data set
      that records the time-dependent frequencies of attacks over a relatively wide
      range of consecutive IP addresses, we successfully uncover intrinsic
      spatiotemporal patterns underlying cyberattacks, where the term "spatio" refers
      to the IP address space. In particular, we focus on analyzing macroscopic
      properties of the attack traffic flows and identify two main patterns with
      distinct spatiotemporal characteristics: deterministic and stochastic.
      Strikingly, there are very few sets of major attackers committing almost all the
      attacks, since their attack "fingerprints" and target selection scheme can be
      unequivocally identified according to the very limited number of unique
      spatiotemporal characteristics, each of which only exists on a consecutive IP
      region and differs significantly from the others. We utilize a number of
      quantitative measures, including the flux-fluctuation law, the Markov state
      transition probability matrix, and predictability measures, to characterize the
      attack patterns in a comprehensive manner. A general finding is that the attack
      patterns possess high degrees of predictability, potentially paving the way to
      anticipating and, consequently, mitigating or even preventing large-scale
      cyberattacks using macroscopic approaches. 

PMID- 25992838
TI  - Interaction of Temperature and Photoperiod Increases Growth and Oil Content in
      the Marine Microalgae Dunaliella viridis.
AB  - Eukaryotic marine microalgae like Dunaliella spp. have great potential as a
      feedstock for liquid transportation fuels because they grow fast and can
      accumulate high levels of triacylgycerides with little need for fresh water or
      land. Their growth rates vary between species and are dependent on environmental
      conditions. The cell cycle, starch and triacylglycerol accumulation are
      controlled by the diurnal light:dark cycle. Storage compounds like starch and
      triacylglycerol accumulate in the light when CO2 fixation rates exceed the need
      of assimilated carbon and energy for cell maintenance and division during the
      dark phase. To delineate environmental effects, we analyzed cell division rates,
      metabolism and transcriptional regulation in Dunaliella viridis in response to
      changes in light duration and growth temperatures. Its rate of cell division was
      increased under continuous light conditions, while a shift in temperature from 25
      degrees C to 35  degrees C did not significantly affect the cell division rate,
      but increased the triacylglycerol content per cell several-fold under continuous
      light. The amount of saturated fatty acids in triacylglycerol fraction was more
      responsive to an increase in temperature than to a change in the light regime.
      Detailed fatty acid profiles showed that Dunaliella viridis incorporated lauric
      acid (C12:0) into triacylglycerol after 24 hours under continuous light.
      Transcriptome analysis identified potential regulators involved in the light and
      temperature-induced lipid accumulation in Dunaliella viridis.

PMID- 25992840
TI  - Unified Approach to Isoindolinones and THIQs via Lewis Acid Catalyzed Domino
      Mukaiyama-Mannich Lactamization/Alkylations: Application in the Synthesis of (+/
      )-Homolaudanosine.
AB  - A novel and efficient synthesis of a variety of isoindolinones and
      tetrahydroisoquinolines via a Lewis acid catalyzed domino Mukaiyama-Mannich
      lactamization/alkylation is achieved. This transformation comprises a sequential
      formation of three new bonds through a one-pot, three-component procedure to
      afford product in moderate to high yields. A concise synthesis of (+/-)
      homolaudanosine (2b) has been achieved using this method. 

PMID- 25992839
TI  - High Protein Diet and Huntington's Disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by the
      huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent
      brain abnormalities, impairments also occur in peripheral tissues. We previously
      reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle
      deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates
      symptoms in HD model mice. It remains unknown whether the dietary protein content
      should be monitored closely in HD patients because the normal protein consumption
      is lower in humans (~15% of total calories) than in mice (~22%). We assessed
      whether dietary protein content affects the urea cycle in HD patients. Thirty HD
      patients were hospitalized and received a standard protein diet (13.7% protein)
      for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5
      days. Urea cycle deficiency was monitored by the blood levels of citrulline and
      ammonia. HD progression was determined by the Unified Huntington's Disease Rating
      Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19
      MUmol/l to 16.30 MUmol/l (p = 0.0378) in HD patients but did not change blood
      ammonia concentration. A 2-year pilot study of 14 HD patients found no
      significant correlation between blood citrulline concentration and HD
      progression. Our results indicated a short period of the HPD did not markedly
      compromise urea cycle function. Blood citrulline concentration is not a reliable
      biomarker of HD progression. 

PMID- 25992841
TI  - The songbird as a percussionist: syntactic rules for non-vocal sound and song
      production in Java sparrows.
AB  - Music and dance are two remarkable human characteristics that are closely
      related. Communication through integrated vocal and motional signals is also
      common in the courtship displays of birds. The contribution of songbird studies
      to our understanding of vocal learning has already shed some light on the
      cognitive underpinnings of musical ability. Moreover, recent pioneering research
      has begun to show how animals can synchronize their behaviors with external
      stimuli, like metronome beats. However, few studies have applied such
      perspectives to unraveling how animals can integrate multimodal communicative
      signals that have natural functions. Additionally, studies have rarely asked how
      well these behaviors are learned. With this in mind, here we cast a spotlight on
      an unusual animal behavior: non-vocal sound production associated with singing in
      the Java sparrow (Lonchura oryzivora), a songbird. We show that male Java
      sparrows coordinate their bill-click sounds with the syntax of their song-note
      sequences, similar to percussionists. Analysis showed that they produced clicks
      frequently toward the beginning of songs and before/after specific song notes. We
      also show that bill-clicking patterns are similar between social fathers and
      their sons, suggesting that these behaviors might be learned from models or
      linked to learning-based vocalizations. Individuals untutored by conspecifics
      also exhibited stereotypical bill-clicking patterns in relation to song-note
      sequence, indicating that while the production of bill clicking itself is
      intrinsic, its syncopation appears to develop with songs. This paints an
      intriguing picture in which non-vocal sounds are integrated with vocal courtship
      signals in a songbird, a model that we expect will contribute to the further
      understanding of multimodal communication. 

PMID- 25992842
TI  - Direct synthesis of a {Co6(III)Fe6(III)} dodecanuclear complex, revealing an
      unprecedented molecular structure type.
AB  - A novel heterometallic Co6Fe6 Schiff base complex, possessing an unprecedented
      {M12(MU-X)22} branched structure (according to the search via the Cambridge
      Structural Database), has been prepared using the "direct synthesis" approach and
      characterized by single crystal X-ray diffraction and magnetometry. 

PMID- 25992843
TI  - Bioinspired Titanium Drug Eluting Platforms Based on a Poly-beta-cyclodextrin
      Chitosan Layer-by-Layer Self-Assembly Targeting Infections.
AB  - In the field of implantable titanium-based biomaterials, infections and
      inflammations are the most common forms of postoperative complications. The
      controlled local delivery of therapeutics from implants through polyelectrolyte
      multilayers (PEMs) has recently emerged as a versatile technique that has shown
      great promise in the transformation of a classical medical implant into a drug
      delivery system. Herein, we report the design and the elaboration of new
      biodegradable multidrug-eluting titanium platforms based on a polyelectrolyte
      multilayer bioactive coating that target infections. These systems were built up
      in mild conditions according to the layer-by-layer (L-b-L) assembly and
      incorporate two biocompatible polysaccharides held together through electrostatic
      interactions. A synthetic, negatively charged beta-cyclodextrin-based polymer
      (PCD), well-known for forming stable and reversible complexes with hydrophobic
      therapeutic agents, was exploited as a multidrug reservoir, and chitosan (CHT), a
      naturally occurring, positively charged polyelectrolyte, was used as a barrier
      for controlling the drug delivery rate. These polyelectrolyte multilayer films
      were strongly attached to the titanium surface through a bioinspired polydopamine
      (PDA) film acting as an adhesive first layer and promoting the robust anchorage
      of PEMs onto the biomaterials. Prior to the multilayer film deposition, the
      interactions between both oppositely charged polyelectrolytes, as well the
      multilayer growth, were monitored by employing surface plasmon resonance (SPR).
      Several PEMs integrating 5, 10, and 15 bilayers were engineered using the dip
      coating strategy, and the polyelectrolyte surface densities were estimated by
      colorimetric titrations and gravimetric analyses. The morphologies of these
      multilayer systems, as well as their naturally occurring degradation in a
      physiological medium, were investigated by scanning electron microscopy (SEM),
      and their thicknesses were measured by means of profilometry and ellipsometry
      studies. Finally, the ability of the coated titanium multilayer devices to act as
      a drug-eluting system and to treat infections was validated with gentamicin, a
      relevant water-soluble antibiotic commonly used in medicine due to its broad
      bactericidal spectrum. 

PMID- 25992844
TI  - Snapshot RGB mapping of skin melanin and hemoglobin.
AB  - The concept of snapshot red-green-blue (RGB) multispectral imaging was applied
      for skin chromophore mapping. Three monochromatic spectral images have been
      extracted from a single RGB image dataset at simultaneous illumination of skin by
      473-, 532-, and 659-nm laser lines. The spectral images were further transformed
      into distribution maps of skin melanin, oxyhemoglobin, and deoxyhemoglobin,
      related to pigmented and vascular skin malformations. The performance and
      clinical potential of the proposed technique are discussed

PMID- 25992845
TI  - Tutorial on use of intraclass correlation coefficients for assessing intertest
      reliability and its application in functional near-infrared spectroscopy-based
      brain imaging.
AB  - Test-retest reliability of neuroimaging measurements is an important concern in
      the investigation of cognitive functions in the human brain. To date, intraclass
      correlation coefficients (ICCs), originally used in interrater reliability
      studies in behavioral sciences, have become commonly used metrics in reliability
      studies on neuroimaging and functional near-infrared spectroscopy (fNIRS).
      However, as there are six popular forms of ICC, the adequateness of the
      comprehensive understanding of ICCs will affect how one may appropriately select,
      use, and interpret ICCs toward a reliability study. We first offer a brief review
      and tutorial on the statistical rationale of ICCs, including their underlying
      analysis of variance models and technical definitions, in the context of
      assessment on intertest reliability. Second, we provide general guidelines on the
      selection and interpretation of ICCs. Third, we illustrate the proposed approach
      by using an actual research study to assess interest reliability of fNIRS-based,
      volumetric diffuse optical tomography of brain activities stimulated by a risk
      decision-making protocol. Last, special issues that may arise in reliability
      assessment using ICCs are discussed and solutions are suggested.

PMID- 25992846
TI  - Correction on the distortion of Scheimpflug imaging for dynamic central corneal
      thickness.
AB  - The measurement of central corneal thickness (CCT) is important in ophthalmology.
      Most studies concerned the value at normal status, while rare ones focused on its
      dynamic changing. The commercial Corvis ST is the only commercial device
      currently available to visualize the two-dimensional image of dynamic corneal
      profiles during an air puff indentation. However, the directly observed CCT
      involves the Scheimpflug distortion, thus misleading the clinical diagnosis. This
      study aimed to correct the distortion for better measuring the dynamic CCTs. The
      optical path was first derived to consider the influence of factors on the use of
      Covis ST. A correction method was then proposed to estimate the CCT at any time
      during air puff indentation. Simulation results demonstrated the feasibility of
      the intuitive-feasible calibration for measuring the stationary CCT and indicated
      the necessity of correction when air puffed. Experiments on three contact lenses
      and four human corneas verified the prediction that the CCT would be
      underestimated when the improper calibration was conducted for air and
      overestimated when it was conducted on contact lenses made of
      polymethylmethacrylate. Using the proposed method, the CCT was finally observed
      to increase by 66 +/- 34 MUm at highest concavity in 48 normal human corneas.

PMID- 25992847
TI  - Crustal movements due to Iceland's shrinking ice caps mimic magma inflow signal
      at Katla volcano.
AB  - Many volcanic systems around the world are located beneath, or in close proximity
      to, ice caps. Mass change of these ice caps causes surface movements, which are
      typically neglected when interpreting surface deformation measurements around
      these volcanoes. These movements can however be significant, and may closely
      resemble movements due to magma accumulation. Here we show such an example, from
      Katla volcano, Iceland. Horizontal movements observed by GPS on the flank of
      Katla have led to the inference of significant inflow of magma into a chamber
      beneath the caldera, starting in 2000, and continuing over several years. We use
      satellite radar interferometry and GPS data to show that between 2001 and 2010,
      the horizontal movements seen on the flank can be explained by the response to
      the long term shrinking of ice caps, and that erratic movements seen at stations
      within the caldera are also not likely to signify magma inflow. It is important
      that interpretations of geodetic measurements at volcanoes in glaciated areas
      consider the effect of ice mass change, and previous studies should be carefully
      reevaluated. 

PMID- 25992848
TI  - Physical activity, body composition and metabolic syndrome in young adults.
AB  - OBJECTIVE: Low physical activity (PA) is a major risk factor for cardiovascular
      and metabolic disorders in all age groups. We measured intensity and volume of PA
      and examined the associations between PA and the metabolic syndrome (MS), its
      components and body composition among young Finnish adults. RESEARCH DESIGN AND
      METHODS: The study comprises 991 men and women born 1985-86, who participated in
      a clinical study during the years 2009-11 which included assessments of
      metabolism, body composition and PA. Objectively measured (SenseWear Armband)
      five-day PA data was available from 737 participants and was expressed in
      metabolic equivalents of task (MET). RESULTS: The prevalence of MS ranged between
      8-10%. Higher total mean volume (MET-hours) or intensity (MET) were negatively
      associated with the risk of MS and separate components of MS, while the time
      spent at sedentary level of PA was positively associated with MS. CONCLUSIONS: MS
      was prevalent in approximately every tenth of the young adults at the age of 24
      years. Higher total mean intensity and volume rates as well as longer duration
      spent at moderate and vigorous PA level had a beneficial impact on the risk of
      MS. Longer time spent at the sedentary level of PA increased the risk of MS.

PMID- 25992850
TI  - IL-2: Change Structure ... Change Function.
AB  - In this issue of Immunity, Spangler et al. and Mitra et al. demonstrate how
      structural changes in the IL-2 molecule alter interactions with the IL-2
      receptor, leading to differential cellular targeting and biochemical responses
      and selective immune consequences.

PMID- 25992849
TI  - The Correlation between Polybrominated Diphenyl Ethers (PBDEs) and Thyroid
      Hormones in the General Population: A Meta-Analysis.
AB  - OBJECTIVE: Certain epidemiological studies have suggested exposure to
      polybrominated diphenyl ethers (PBDEs) affect the production and secretion of
      thyroid hormones (TH); however, conflicting results have been reported in
      different studies. There is not a convincing conclusion about this debate to
      date. MATERIALS AND METHODS: To perform a meta-analysis determining if there are
      correlations between PBDEs exposure and the serum levels of TH. Medical and
      scientific literature databases were searched for articles that met the
      eligibility criteria. The included articles were assessed for methodological
      quality. The correlation coefficient values or regression coefficient values
      between PBDEs and thyroid stimulating hormone (TSH) or total thyroxine (TT4) from
      each article were used for analysis. DATA SYNTHESIS: Sixteen articles were
      included in this meta-analysis. Pearson correlation coefficients (r) were
      directly collected or calculated from data given in the articles. Then, Fisher's
      z transformation was performed to convert each correlation coefficient to an
      approximately normal distribution. For z values between PBDEs exposure and TSH
      levels, the pooled z value for 18 studies was 0.08 (95% CI: -0.06, 0.22), and
      indicated significant heterogeneity (I2 values = 90.7%). Subgroup analysis was
      performed based on the median values of serum PBDEs in each study, there was not
      significant heterogeneity in each of the four subgroups (I2 values <30%). In meta
      analysis of z values between PBDEs exposure and the levels of TT4, the pooled z
      value for 11 studies was -0.02 (95% CI: -0.11, 0.08), and also indicated
      significant heterogeneity (I2 values = 57.6%). Similar subgroup analysis was done
      for the PBDEs exposures and the levels of TT4. No significant heterogeneity was
      shown in either of the two subgroups (I2 values = 0). CONCLUSION: The findings in
      our meta-analysis indicate the effects of PBDEs on thyroid function may mainly
      depend on PBDEs exposure and their levels found in serum. The relationship
      between PBDEs exposure and changes in thyroid function seem to fit an approximate
      u-shaped curve. These predictions await further verification, namely a
      prospective longitudinal study.

PMID- 25992851
TI  - New lamp posts allow for new views of the immunological synapse.
AB  - Using new rapid, super-resolution imaging methods, Ritter et al. (2015) define
      the early events of immunological synapse formation and granule release.

PMID- 25992852
TI  - Germinal center quality control: death by Fas.
AB  - Fas is a cell surface death receptor critical for immune regulation. In this
      issue of Immunity, Butt et al. (2015) show that Fas eliminates B cells that have
      become uncoupled from positive and negative selection in the germinal center.

PMID- 25992853
TI  - Kruppel-ling of IRF4-Dependent DCs into Two Functionally Distinct DC Subsets.
AB  - IRF4-dependent DCs have been associated with induction of both Th1 and Th17
      cells. In this issue of Immunity, Tussiwand et al. (2015) demonstrate that a
      dependence on KLF4 identifies a subset of IRF4-dependent DC that preferentially
      promotes Th2 cell differentiation.

PMID- 25992854
TI  - Thymic selection: to thine own self be true.
AB  - It has been shown that self-reactive T cells can be detected in the periphery. In
      this issue of Immunity, Yu et al. (2015) show that clonal deletion prunes the T
      cell repertoire but does not eliminate self-reactive T cell clones.

PMID- 25992855
TI  - Cervicovaginal microbiota: simple is better.
AB  - Vaginal microbiota differs within individuals and between human populations.
      Anahtar et al. (2015) identify a specific vaginal cervicotype commonly found in
      healthy South African women that causes localized inflammation including
      activation of antigen-presenting cells and vaginal recruitment of HIV target
      cells.

PMID- 25992856
TI  - Long noncoding RNA in hematopoiesis and immunity.
AB  - Dynamic gene expression during cellular differentiation is tightly coordinated by
      transcriptional and post-transcriptional mechanisms. An emerging theme is the
      central role of long noncoding RNAs (lncRNAs) in the regulation of this
      specificity. Recent advances demonstrate that lncRNAs are expressed in a lineage
      specific manner and control the development of several cell types in the
      hematopoietic system. Moreover, specific lncRNAs are induced to modulate innate
      and adaptive immune responses. lncRNAs can function via RNA-DNA, RNA-RNA, and RNA
      protein target interactions. As a result, they affect several stages of gene
      regulation, including chromatin modification, mRNA biogenesis, and protein
      signaling. We discuss recent advances, future prospects, and challenges in
      understanding the roles of lncRNAs in immunity and immune-mediated diseases. 

PMID- 25992857
TI  - The virome in host health and disease.
AB  - The mammalian virome includes diverse commensal and pathogenic viruses that evoke
      a broad range of immune responses from the host. Sustained viral immunomodulation
      is implicated in a variety of inflammatory diseases, but also confers unexpected
      benefits to the host. These outcomes of viral infections are often dependent on
      host genotype. Moreover, it is becoming clear that the virome is part of a
      dynamic network of microorganisms that inhabit the body. Therefore, viruses can
      be viewed as a component of the microbiome, and interactions with commensal
      bacteria and other microbial agents influence their behavior. This piece is a
      review of our current understanding of how the virome, together with other
      components of the microbiome, affects the function of the host immune system to
      regulate health and disease. 

PMID- 25992858
TI  - Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through
      Distinct Conformational Mechanisms.
AB  - Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates immune cell
      homeostasis and has been used to treat a range of disorders including cancer and
      autoimmune disease. IL-2 signals via interleukin-2 receptor-beta (IL-2Rbeta):IL
      2Rgamma heterodimers on cells expressing high (regulatory T cells, Treg) or low
      (effector cells) amounts of IL-2Ralpha (CD25). When complexed with IL-2, certain
      anti-cytokine antibodies preferentially stimulate expansion of Treg (JES6-1) or
      effector (S4B6) cells, offering a strategy for targeted disease therapy. We found
      that JES6-1 sterically blocked the IL-2:IL-2Rbeta and IL-2:IL-2Rgamma
      interactions, but also allosterically lowered the IL-2:IL-2Ralpha affinity
      through a "triggered exchange" mechanism favoring IL-2Ralpha(hi) Treg cells,
      creating a positive feedback loop for IL-2Ralpha(hi) cell activation. Conversely,
      S4B6 sterically blocked the IL-2:IL-2Ralpha interaction, while also
      conformationally stabilizing the IL-2:IL-2Rbeta interaction, thus stimulating all
      IL-2-responsive immune cells, particularly IL-2Rbeta(hi) effector cells. These
      insights provide a molecular blueprint for engineering selectively potentiating
      therapeutic antibodies.

PMID- 25992859
TI  - Interleukin-2 activity can be fine tuned with engineered receptor signaling
      clamps.
AB  - Interleukin-2 (IL-2) regulates lymphocyte function by signaling through
      heterodimerization of the IL-2Rbeta and gammac receptor subunits. IL-2 is of
      considerable therapeutic interest, but harnessing its actions in a controllable
      manner remains a challenge. Previously, we have engineered an IL-2 "superkine"
      with enhanced affinity for IL-2Rbeta. Here, we describe next-generation IL-2
      variants that function as "receptor signaling clamps." They retained high
      affinity for IL-2Rbeta, inhibiting binding of endogenous IL-2, but their
      interaction with gammac was weakened, attenuating IL-2Rbeta-gammac
      heterodimerization. These IL-2 analogs acted as partial agonists and
      differentially affected lymphocytes poised at distinct activation thresholds.
      Moreover, one variant, H9-RETR, antagonized IL-2 and IL-15 better than blocking
      antibodies against IL-2Ralpha or IL-2Rbeta. Furthermore, this mutein prolonged
      survival in a model of graft-versus-host disease and blocked spontaneous
      proliferation of smoldering adult T cell leukemia (ATL) T cells. This receptor
      clamping approach might be a general mechanism-based strategy for engineering
      cytokine partial agonists for therapeutic immunomodulation.

PMID- 25992860
TI  - Actin depletion initiates events leading to granule secretion at the
      immunological synapse.
AB  - Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally
      infected and tumor cells. To understand the temporal relationships between key
      events leading to secretion, we used high-resolution 4D imaging. CTLs approached
      targets with actin-rich projections at the leading edge, creating an initially
      actin-enriched contact with rearward-flowing actin. Within 1 min, cortical actin
      reduced across the synapse, T cell receptors (TCRs) clustered centrally to form
      the central supramolecular activation cluster (cSMAC), and centrosome
      polarization began. Granules clustered around the moving centrosome within 2.5
      min and reached the synapse after 6 min. TCR-bearing intracellular vesicles were
      delivered to the cSMAC as the centrosome docked. We found that the centrosome and
      granules were delivered to an area of membrane with reduced cortical actin
      density and phospholipid PIP2. These data resolve the temporal order of events
      during synapse maturation in 4D and reveal a critical role for actin depletion in
      regulating secretion.

PMID- 25992861
TI  - Asymmetric Action of STAT Transcription Factors Drives Transcriptional Outputs
      and Cytokine Specificity.
AB  - Interleukin-6 (IL-6) and IL-27 signal through a shared receptor subunit and
      employ the same downstream STAT transcription proteins, but yet are ascribed
      unique and overlapping functions. To evaluate the specificity and redundancy for
      these cytokines, we quantified their global transcriptomic changes and determined
      the relative contributions of STAT1 and STAT3 using genetic models and chromatin
      immunoprecipitation-sequencing (ChIP-seq) approaches. We found an extensive
      overlap of the transcriptomes induced by IL-6 and IL-27 and few examples in which
      the cytokines acted in opposition. Using STAT-deficient cells and T cells from
      patients with gain-of-function STAT1 mutations, we demonstrated that STAT3 is
      responsible for the overall transcriptional output driven by both cytokines,
      whereas STAT1 is the principal driver of specificity. STAT1 cannot compensate in
      the absence of STAT3 and, in fact, much of STAT1 binding to chromatin is STAT3
      dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon
      STAT3's action.

PMID- 25992862
TI  - Klf4 expression in conventional dendritic cells is required for T helper 2 cell
      responses.
AB  - The two major lineages of classical dendritic cells (cDCs) express and require
      either IRF8 or IRF4 transcription factors for their development and function.
      IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses,
      whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and
      Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4
      (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell
      responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell
      responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA)
      immunization, and house dust mite (HDM) challenge without affecting cytotoxic T
      lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus,
      Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion
      reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4
      expressing cDCs subsets in several tissues. These results indicate that Klf4
      guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.

PMID- 25992863
TI  - Clonal Deletion Prunes but Does Not Eliminate Self-Specific alphabeta CD8(+) T
      Lymphocytes.
AB  - It has long been thought that clonal deletion efficiently removes almost all self
      specific T cells from the peripheral repertoire. We found that self-peptide MHC
      specific CD8(+) T cells in the blood of healthy humans were present in
      frequencies similar to those specific for non-self antigens. For the Y chromosome
      encoded SMCY antigen, self-specific T cells exhibited only a 3-fold lower average
      frequency in males versus females and were anergic with respect to peptide
      activation, although this inhibition could be overcome by a stronger stimulus. We
      conclude that clonal deletion prunes but does not eliminate self-specific T cells
      and suggest that to do so would create holes in the repertoire that pathogens
      could readily exploit. In support of this hypothesis, we detected T cells
      specific for all 20 amino acid variants at the p5 position of a hepatitis C virus
      epitope in a random group of blood donors.

PMID- 25992864
TI  - Epidermal Fatty Acid binding protein promotes skin inflammation induced by high
      fat diet.
AB  - Defining specific cellular and molecular mechanisms in most obesity-related
      diseases remains an important challenge. Here we report a serendipitous finding
      that consumption of a high-fat diet (HFD) greatly increased the occurrence of
      skin lesions in C57BL/6 mice. We demonstrated that HFD induced the accumulation
      of a specific type of CD11c(+) macrophages in skin preceding detectable lesions.
      These cells primed skin to induce IL-1beta and IL-18 signaling, which further
      promoted the cytokines IFN-gamma- and IL-17-mediated skin inflammation.
      Mechanistically, epidermal fatty acid binding protein (E-FABP) was significantly
      upregulated in skin of obese mice, which coupled lipid droplet formation and
      NLRP3 inflammasome activation. Deficiency of E-FABP in obese mice decreased
      recruitment of CD11c(+) macrophages in skin tissues, reduced production of IL
      1beta and IL-18, and consequently dampened activation of effector T cells.
      Furthermore, E-FABP-deficient mice are completely resistant to HFD-induced skin
      lesions. Collectively, E-FABP represents a molecular sensor triggering HFD
      induced skin inflammation.

PMID- 25992865
TI  - Cervicovaginal bacteria are a major modulator of host inflammatory responses in
      the female genital tract.
AB  - Colonization by Lactobacillus in the female genital tract is thought to be
      critical for maintaining genital health. However, little is known about how
      genital microbiota influence host immune function and modulate disease
      susceptibility. We studied a cohort of asymptomatic young South African women and
      found that the majority of participants had genital communities with low
      Lactobacillus abundance and high ecological diversity. High-diversity communities
      strongly correlated with genital pro-inflammatory cytokine concentrations in both
      cross-sectional and longitudinal analyses. Transcriptional profiling suggested
      that genital antigen-presenting cells sense gram-negative bacterial products in
      situ via Toll-like receptor 4 signaling, contributing to genital inflammation
      through activation of the NF-kappaB signaling pathway and recruitment of
      lymphocytes by chemokine production. Our study proposes a mechanism by which
      cervicovaginal microbiota impact genital inflammation and thereby might affect a
      woman's reproductive health, including her risk of acquiring HIV.

PMID- 25992866
TI  - Application of cold patch in relieving pain after transepithelial photorefractive
      keratectomy.
AB  - BACKGROUND: A return toward toward photorefractive keratectomy has occurred due
      to better corneal stability and fewer corneal flap complications; however, pain
      remains a major drawback of the procedure. Currently, clinical pain control
      measures focus on the administration of pain medications, which may delay corneal
      epithelial healing and has, occasionally, led to serious corneal toxicity.
      OBJECTIVES: To investigate the safety and efficacy of a cold patch on
      postoperative pain and other relevant consequences of transepithelial
      photorefractive keratectomy. METHODS: A prospective, randomized controlled study
      was conducted. Forty patients (80 eyes) scheduled to undergo transepithelial
      photorefractive keratectomy for myopia or myopic astigmatism were randomly and
      equally assigned to be treated with ice-cold balanced salt solution during
      surgery (wash group) or to wear a postoperative cold patch on the eye for 24 h.
      The main outcomes were pain score on a visual analogue scale, postoperative
      eyelid edema, conjunctival hyperemia, epithelial healing time, haze and
      postoperative best-corrected visual acuity. RESULTS: All patients completed the
      final tests. Demographic characteristics and pain scores during surgery were
      similar between the two groups. The mean postoperative pain scores of patients in
      the cold patch group at 8 h, 16 h and 24 h were significantly lower than those of
      patients in the wash group. Scores for postoperative eyelid edema and
      conjunctival hyperemia in the cold patch group were also lower than in the wash
      group. Patients in the cold patch group used fewer painkillers. Epithelial
      healing time, haze and early recovery of visual acuity were similar between the
      two groups. No eyelid frostbite was observed. CONCLUSION: Wearing a cold patch on
      the eye after transepithelial photorefractive keratectomy effectively relieved
      pain and inflammation, and reduced the use of painkillers without any side
      effects.

PMID- 25992867
TI  - Primer for immunohistochemistry on cryosectioned rat brain tissue: example
      staining for microglia and neurons.
AB  - Immunohistochemistry is a widely used technique for detecting the presence,
      location, and relative abundance of antigens in situ. This introductory level
      protocol describes the reagents, equipment, and techniques required to complete
      immunohistochemical staining of rodent brain tissue, using markers for microglia
      and neuronal elements as an example. Specifically, this paper is a step-by-step
      protocol for fluorescent visualization of microglia and neurons via
      immunohistochemistry for Iba1 and Pan-neuronal, respectively. Fluorescence double
      labeling is particularly useful for the localization of multiple proteins within
      the same sample, providing the opportunity to accurately observe interactions
      between cell types, receptors, ligands, and/or the extracellular matrix in
      relation to one another as well as protein co-localization within a single cell.
      Unlike other visualization techniques, fluorescence immunohistochemistry staining
      intensity may decrease in the weeks to months following staining, unless
      appropriate precautions are taken. Despite this limitation, in many applications
      fluorescence double-labeling is preferred over alternatives such as 3,3'
      diaminobenzidine tetrahydrochloride (DAB) or alkaline phosphatase (AP), as
      fluorescence is more time efficient and allows for more precise differentiation
      between two or more markers. The discussion includes troubleshooting tips and
      advice to promote success. 

PMID- 25992868
TI  - Impact of political violence on the mental health of school children in Egypt.
AB  - BACKGROUND: Since the beginning of the Egyptian political conflict, Tahrir Square
      has been the epicentre of intense political violence. Students attending schools
      located near this square witnessed and/or directly experienced the consequences
      of a series of violent events. AIM: This study will investigate the presence of
      psychiatric symptoms in children attending these schools to explore patterns of
      responses according to their perceptions of the revolution on their lives,
      adjusted for, gender and socio-economic status. METHOD: A descriptive cross
      sectional study conducted with 515 Egyptian school children attending government,
      experimental, and private language schools located within 1 km of Tahrir Square.
      To assess psychiatric symptoms in these children, a specially designed
      questionnaire was used to detect, depression, anxiety, and post-traumatic stress
      disorder (PTSD) symptoms and impairments. RESULTS: Children attending schools
      near Tahrir Square showed high rates of depression, PTSD and anxiety symptoms.
      The risk factors identified for developing psychiatric symptoms were a negative
      perception of the effect of the revolution, knowing someone exposed to trauma
      during the events, female gender and low socio-economic class. DISCUSSION: These
      results highlight the need for large-scale studies to explore the consequences of
      ongoing political violence on children and to establish baseline data on the
      mental health of Egyptian children.

PMID- 25992869
TI  - Identifying the causative proteins of similar side effect pairs to explore the
      common molecular basis of these side effects.
AB  - Drug side effects, or adverse drug reactions (ADRs), have become a major public
      health concern and often cause drug development failure and withdrawal. Some ADRs
      always occur concomitantly. Therefore, identifying these ADRs and their common
      molecular basis can better promote their prevention and treatment. In this paper
      we predicted the potential proteins for ADR pairs with similar mechanisms based
      on three layers of information: (i) the drug co-occurrence between a pair of
      ADRs; (ii) the correlation between a protein and an ADR pair based on the co
      occurrence of drugs and (iii) the interaction between these proteins within the
      protein-protein interaction (PPI) network. The methods of randomization and
      functional annotation are used to investigate and analyze the relation between
      causative proteins and similar ADR pairs. The prediction accuracy of the relation
      between similar ADR pairs and related proteins reached 80%, and it increases with
      the number of drugs shared by the ADR pairs. From the ADR network made of single
      ADRs from predicted similar ADR pairs, we found that some ADRs are involved in
      multiple ADR pairs. The functional analysis of these ADR-related proteins
      suggests that a similar molecular basis is shared by multiple ADR pairs
      containing the same ADR, and these ADR pairs are almost caused by the same drug
      sets. The results of this study are reliable and provide a theoretical basis for
      the better prevention and treatment of ADRs that always occur concomitantly. 

PMID- 25992870
TI  - Isolation and transplantation of different aged murine thymic grafts.
AB  - The mechanisms that regulate the efficacy of thymic selection remain ill-defined.
      The method presented here allows in vivo analyses of the development and
      selection of T cells specific for self and foreign antigens. The approach entails
      implantation of thymic grafts derived from various aged mice into immunodeficient
      scid recipients. Over a relatively short period of time the recipients are fully
      reconstituted with T cells derived from the implanted thymus graft. Only
      thymocytes seeding the thymus at the time of isolation undergo selection and
      develop into mature T cells. As such, changes in the nature and specificity of
      the engrafted T cells as a function of age-dependent thymic events can be
      assessed. Although technical expertise is required for successful thymic
      transplantation, this method provides a unique strategy to study in vivo a wide
      range of pathologies that are due to or a result of aberrant thymic function
      and/or homeostasis. 

PMID- 25992871
TI  - A dynamic stroke treatment paradigm.

PMID- 25992872
TI  - Investigation on legal problems encountered by emergency medicine physicians in
      Turkey.
AB  - BACKGROUND: Medicine is a profession that carries certain risks. One risky area
      of practice is the emergency department. Emergency physicians diagnose and treat
      a high volume of patients, and are also responsible for preparing reports for
      forensic cases. In this study, we aim to investigate emergency physicians' legal
      administrative problems and reveal their level of understanding on forensic
      cases. METHODS: An electronic questionnaire form was prepared after the approval
      of an ethical committee. This form was sent to the residents, specialists and
      academicians of emergency medicine by e-mail. The physicians were asked to fill
      out the form online. All the gathered data was analyzed. Descriptive statistics
      were presented as frequency percentages with mean and standard deviation. Chi
      square tests were used to compare the groups. Correlation between number of
      complaint cases and age, sex, career, institution, and duration of service in
      emergency department were investigated. p<0.05 was considered statistically
      significant. RESULTS: 294 physicians participated in the questionnaire. According
      to the questionnaire, 170 of the physicians were reported to the patient
      communication units due to medical malpractice. Mean number of compliant reports
      was 3.20+/-3.5. 29 of the physicians received administrative penalties. 42 of the
      physicians were judged in the court for medical malpractice. 1 physician was
      fined 5000 Turkish Liras as a result of these judgments. CONCLUSION: We found
      that the number of complaint reports is negatively correlated with duration of
      service in emergency medicine and age. There was a significant difference between
      number of complaint reports and career (p<0.05). The physicians' level of
      awareness on forensic cases was found to be insufficient. Lack of legislation
      knowledge may be an important cause of complaint reports concerning emergency
      physicians, who have a high load of patients. Thus, we think that increasing the
      frequency of post-graduate education sessions and periodical reviews might be
      beneficial.

PMID- 25992873
TI  - Practical Events in the Management of a Collodion Baby.

PMID- 25992875
TI  - Microscale heterogeneity explains experimental variability and non-linearity in
      soil organic matter mineralisation.
AB  - Soil respiration represents the second largest CO2 flux from terrestrial
      ecosystems to the atmosphere, and a small rise could significantly contribute to
      further increase in atmospheric CO2. Unfortunately, the extent of this effect
      cannot be quantified reliably, and the outcomes of experiments designed to study
      soil respiration remain notoriously unpredictable. In this context, the
      mathematical simulations described in this article suggest that assumptions of
      linearity and presumed irrelevance of micro-scale heterogeneity, commonly made in
      quantitative models of microbial growth in subsurface environments and used in
      carbon stock models, do not appear warranted. Results indicate that microbial
      growth is non-linear and, at given average nutrient concentrations, strongly
      dependent on the microscale distribution of both nutrients and microbes. These
      observations have far-reaching consequences, in terms of both experiments and
      theory. They indicate that traditional, macroscopic soil measurements are
      inadequate to predict microbial responses, in particular to rising temperature
      conditions, and that an explicit account is required of microscale heterogeneity.
      Furthermore, models should evolve beyond traditional, but overly simplistic,
      assumptions of linearity of microbial responses to bulk nutrient concentrations.
      The development of a new generation of models along these lines, and in
      particular incorporating upscaled information about microscale processes, will
      undoubtedly be challenging, but appears to be key to understanding the extent to
      which soil carbon mineralization could further accelerate climate change. 

PMID- 25992874
TI  - The longitudinal transcriptomic response of the substantia nigra to intrastriatal
      6-hydroxydopamine reveals significant upregulation of regeneration-associated
      genes.
AB  - We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in
      the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat
      (rattus norvegicus) would identify cellular responses during the degenerative
      process that could be axoprotective. Specifically, we hypothesized that genes
      expressed within the SN that followed a profile of being highly upregulated early
      after the lesion (during active axonal degeneration) and then progressively
      declined to baseline over 16 weeks as DA neurons died are indicative of potential
      protective responses to the striatal 6-OHDA insult. Utilizing a kappa-means
      cluster analysis strategy, we demonstrated that one such cluster followed this
      hypothesized expression pattern over time, and that this cluster contained
      several interrelated transcripts that are classified as regeneration-associated
      genes (RAGs) including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1,
      Rab15,Lifr, Trib3, Tgfb1, and Sema3c. All exemplar transcripts tested from this
      cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11) were validated by qPCR and a
      smaller subset (Sprr1a, Gadd45a and Sox11) were shown to be exclusively localized
      to SN DA neurons using a dual label approach with RNAScope in situ hybridization
      and immunohistochemistry. Upregulation of RAGs is typically associated with the
      response to axonal injury in the peripheral nerves and was not previously
      reported as part of the axodegenerative process for DA neurons of the SN.
      Interestingly, as part of this cluster, other transcripts were identified based
      on their expression pattern but without a RAG provenance in the literature. These
      "RAG-like" transcripts need further characterization to determine if they possess
      similar functions to or interact with known RAG transcripts. Ultimately, it is
      hoped that some of the newly identified axodegeneration-reactive transcripts
      could be exploited as axoprotective therapies in PD and other neurodegenerative
      diseases. 

PMID- 25992876
TI  - C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during
      both planktonic and biofilm modes of growth.
AB  - Stress response plays an important role on microbial adaptation under hostile
      environmental conditions. It is generally unclear how the signaling transduction
      pathway mediates a stress response in planktonic and biofilm modes of microbial
      communities simultaneously. Here, we showed that metalloid tellurite (TeO3(2-))
      exposure induced the intracellular content of the secondary messenger cyclic di
      GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC
      and SiaD, were responsible for the increased intracellular content of c-di-GMP.
      Enhanced c-di-GMP levels by TeO3(2-) further increased P. aeruginosa biofilm
      formation and resistance to TeO3(2-). P. aeruginosa DeltasadCDeltasiaD and
      PAO1/p(lac)-yhjH mutants with low intracellular c-di-GMP content were more
      sensitive to TeO3(2-) exposure and had low relative fitness compared to the wild
      type PAO1 planktonic and biofilm cultures exposed to TeO3(2-). Our study provided
      evidence that c-di-GMP level can play an important role in mediating stress
      response in microbial communities during both planktonic and biofilm modes of
      growth.

PMID- 25992877
TI  - Intraoperative tight glucose control using hyperinsulinemic normoglycemia
      increases delirium after cardiac surgery.
AB  - BACKGROUND: Postoperative delirium is common in patients recovering from cardiac
      surgery. Tight glucose control has been shown to reduce mortality and morbidity.
      Therefore, the authors sought to determine the effect of tight intraoperative
      glucose control using a hyperinsulinemic-normoglycemic clamp approach on
      postoperative delirium in patients undergoing cardiac surgery. METHODS: The
      authors enrolled 198 adult patients having cardiac surgery in this randomized,
      double-blind, single-center trial. Patients were randomly assigned to either
      tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp
      (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin
      administration with blood glucose target, <150 mg/dl). Delirium was assessed
      using a comprehensive delirium battery. The authors considered patients to have
      experienced postoperative delirium when Confusion Assessment Method testing was
      positive at any assessment. A positive Confusion Assessment Method was defined by
      the presence of features 1 (acute onset and fluctuating course) and 2
      (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness).
      RESULTS: Patients randomized to tight glucose control were more likely to be
      diagnosed as being delirious than those assigned to routine glucose control (26
      of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after
      adjusting for preoperative usage of calcium channel blocker and American Society
      of Anesthesiologist physical status. Delirium severity, among patients with
      delirium, was comparable with each glucose management strategy. CONCLUSION:
      Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after
      cardiac surgery, but not its severity.

PMID- 25992878
TI  - Vision training methods for sports concussion mitigation and management.
AB  - There is emerging evidence supporting the use vision training, including light
      board training tools, as a concussion baseline and neuro-diagnostic tool and
      potentially as a supportive component to concussion prevention strategies. This
      paper is focused on providing detailed methods for select vision training tools
      and reporting normative data for comparison when vision training is a part of a
      sports management program. The overall program includes standard vision training
      methods including tachistoscope, Brock's string, and strobe glasses, as well as
      specialized light board training algorithms. Stereopsis is measured as a means to
      monitor vision training affects. In addition, quantitative results for vision
      training methods as well as baseline and post-testing *A and Reaction Test
      measures with progressive scores are reported. Collegiate athletes consistently
      improve after six weeks of training in their stereopsis, *A and Reaction Test
      scores. When vision training is initiated as a team wide exercise, the incidence
      of concussion decreases in players who participate in training compared to
      players who do not receive the vision training. Vision training produces
      functional and performance changes that, when monitored, can be used to assess
      the success of the vision training and can be initiated as part of a sports
      medical intervention for concussion prevention. 

PMID- 25992879
TI  - The impact of improving suicide death classification in South Korea: a comparison
      with Japan and Hong Kong.
AB  - INTRODUCTION: The suicide rate of South Korea has increased dramatically during
      the past decades, as opposed to steadily decreasing trends in Japan and Hong
      Kong. Although the recent increase of suicide in South Korea may be related to
      changing socioeconomic conditions and other contextual factors, it may also
      reflect, in part, a reduction of misidentified suicide cases due to improving
      classification of manner of death. METHOD: We compared the annual proportional
      change of suicide, undetermined death, and accidental death from South Korea with
      those of Japan and Hong Kong from 1992 to 2011; a greater proportional change of
      the manner-of-death categories during the period is indicative of a relatively
      less stable registration and hence a greater potential for misclassification bias
      on reported suicide trends. Subgroup analyses stratifying the deaths by methods
      were also conducted. To estimate the impact, the age-standardized rates of these
      three death categories in each site were calculated. RESULTS: We found that,
      during the 20-year observation period, the proportional change of suicide,
      undetermined death, and accidental death in South Korea was significantly greater
      than Japan and Hong Kong. Similar observations were made in subgroup analyses.
      While death rates of the three manners in Japan and Hong Kong generally moved in
      a parallel fashion, the increase of suicide in South Korea occurred concomitantly
      with a significant reduction of its accidental death rate. 43% of the increase in
      suicides could be attributed to the decrease in accidental deaths, while 57% of
      the increase could be due to fundamental causes. CONCLUSION: Our data suggest
      that, during the mid-1990s and after, the increasing burden of suicide in South
      Korea initially was masked, in part, by misclassification. Thus, the later
      apparently rapid increase of suicides reflected steadily improving classification
      of manner of death, as well as a more fundamental increase in the suicide rate.

PMID- 25992881
TI  - A network flow-based method to predict anticancer drug sensitivity.
AB  - Predicting anticancer drug sensitivity can enhance the ability to individualize
      patient treatment, thus making development of cancer therapies more effective and
      safe. In this paper, we present a new network flow-based method, which utilizes
      the topological structure of pathways, for predicting anticancer drug
      sensitivities. Mutations and copy number alterations of cancer-related genes are
      assumed to change the pathway activity, and pathway activity difference before
      and after drug treatment is used as a measure of drug response. In our model,
      Contributions from different genetic alterations are considered as free
      parameters, which are optimized by the drug response data from the Cancer Genome
      Project (CGP). 10-fold cross validation on CGP data set showed that our model
      achieved comparable prediction results with existing elastic net model using much
      less input features. 

PMID- 25992882
TI  - Collective Movement in the Tibetan Macaques (Macaca thibetana): Early Joiners
      Write the Rule of the Game.
AB  - Collective behavior has recently attracted a great deal of interest in both
      natural and social sciences. While the role of leadership has been closely
      scrutinized, the rules used by joiners in collective decision making have
      received far less attention. Two main hypotheses have been proposed concerning
      these rules: mimetism and quorum. Mimetism predicts that individuals are
      increasingly likely to join collective behavior as the number of participants
      increases. It can be further divided into selective mimetism, where relationships
      among the participants affect the process, and anonymous mimetism, where no such
      effect exists. Quorum predicts that a collective behavior occurs when the number
      of participants reaches a threshold. To probe into which rule is used in
      collective decision making, we conducted a study on the joining process in a
      group of free-ranging Tibetan macaques (Macaca thibetana) in Huangshan, China
      using a combination of all-occurrence and focal animal sampling methods. Our
      results show that the earlier individuals joined movements, the more central a
      role they occupied among the joining network. We also found that when less than
      three adults participated in the first five minutes of the joining process, no
      entire group movement occurred subsequently. When the number of these early
      joiners ranged from three to six, selective mimetism was used. This means higher
      rank or closer social affiliation of early joiners could be among the factors of
      deciding whether to participate in movements by group members. When the number of
      early joiners reached or exceeded seven, which was the simple majority of the
      group studied, entire group movement always occurred, meaning that the quorum
      rule was used. Putting together, Macaca thibetana used a combination of selective
      mimetism and quorum, and early joiners played a key role in deciding which rule
      should be used. 

PMID- 25992883
TI  - Stereochemical Course of Wittig Rearrangements of Dihydropyran Allyl Propargyl
      Ethers.
AB  - [2,3]-Wittig rearrangements of sugar-derived dihydropyran allyl propargyl ethers
      located at the 2- or 4-position have been studied as useful means for extending
      the carbon chains of the 4- or 2-position with chirality transfer. The
      stereochemical course of these reactions depends on the following factors: (1)
      deprotonation of pro-R or pro-S-H, (2) equilibration of the lithiated stereogenic
      carbanion, (3) conformational inversion during the rearrangement, and (4)
      concerted [2,3]- or [1,2]-Wittig rearrangement. In some cases, a stepwise
      mechanism that involves the allyl-C-O bond cleavage is shared as the first step
      by both the [2,3]- and [1,2]-Wittig rearrangements. The stereochemical courses of
      the rearrangements are compared among the lithiated reactants to determine the
      reaction pathways. These mechanisms in the polyoxygenated dihydropyran ring
      system were further supported by DFT calculations. 

PMID- 25992880
TI  - Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and
      Women's Health.
AB  - In 1994, following work from this laboratory, it was reported that estrone-3-O
      sulfamate irreversibly inhibits a new potential hormone-dependent cancer target
      steroid sulfatase (STS). Subsequent drug discovery projects were initiated to
      develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have
      led to steroidal and nonsteroidal drugs in numerous preclinical and clinical
      trials, with promising results in oncology and women's health, including
      endometriosis. Drugs have been designed to inhibit STS, e.g., Irosustat, as
      innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as
      multitargeting agents for hormone-independent tumors, such as the steroidal
      STX140 and nonsteroidal counterparts, acting inter alia through microtubule
      disruption. The aryl sulfamate pharmacophore is highly versatile, operating via
      three distinct mechanisms of action, and imbues attractive pharmaceutical
      properties. This Perspective gives a personal view of the work leading both to
      the therapeutic concepts and these drugs, their current status, and how they
      might develop in the future. 

PMID- 25992884
TI  - Serum calprotectin, CD26 and EGF to establish a panel for the diagnosis of lung
      cancer.
AB  - Lung cancer is the most lethal neoplasia, and an early diagnosis is the best way
      for improving survival. Symptomatic patients attending Pulmonary Services could
      be diagnosed with lung cancer earlier if high-risk individuals are promptly
      separated from healthy individuals and patients with benign respiratory
      pathologies. We searched for a convenient non-invasive serum test to define which
      patients should have more immediate clinical tests. Six cancer-associated
      molecules (HB-EGF, EGF, EGFR, sCD26, VEGF, and Calprotectin) were investigated in
      this study. Markers were measured in serum by specific ELISAs, in an unselected
      population that included 72 lung cancer patients of different histological types
      and 56 control subjects (healthy individuals and patients with benign pulmonary
      pathologies). Boosted regression and random forests analysis were conducted for
      the selection of the best candidate biomarkers. A remarkable discriminatory
      capacity was observed for EGF, sCD26, and especially for Calprotectin, these
      three molecules constituting a marker panel boasting a sensitivity of 83% and
      specificity of 87%, resulting in an associated misclassification rate of 15%.
      Finally, an algorithm derived by logistic regression and a nomogram allowed
      generating classification scores in terms of the risk of a patient of suffering
      lung cancer. In conclusion, we propose a non-invasive test to identify patients
      at high-risk for lung cancer from a non-selected population attending a Pulmonary
      Service. The efficacy of this three-marker panel must be tested in a larger
      population for lung cancer. 

PMID- 25992886
TI  - Elasto-Capillary Folding Using Stop-Programmable Hinges Fabricated by 3D Micro
      Machining.
AB  - We show elasto-capillary folding of silicon nitride objects with accurate folding
      angles between flaps of (70.6 +/- 0.1) degrees  and demonstrate the feasibility
      of such accurate micro-assembly with a final folding angle of 90 degrees . The
      folding angle is defined by stop-programmable hinges that are fabricated starting
      from silicon molds employing accurate three-dimensional corner lithography. This
      nano-patterning method exploits the conformal deposition and the subsequent timed
      isotropic etching of a thin film in a 3D shaped silicon template. The technique
      leaves a residue of the thin film in sharp concave corners which can be used as
      an inversion mask in subsequent steps. Hinges designed to stop the folding at
      70.6 degrees  were fabricated batchwise by machining the V-grooves obtained by
      KOH etching in (110) silicon wafers; 90 degrees  stop-programmable hinges were
      obtained starting from silicon molds obtained by dry etching on (100) wafers. The
      presented technique has potential to achieve any folding angle and opens a new
      route towards creating structures with increased complexity, which will
      ultimately lead to a novel method for device fabrication. 

PMID- 25992885
TI  - Genomic instability of osteosarcoma cell lines in culture: impact on the
      prediction of metastasis relevant genes.
AB  - BACKGROUND: Osteosarcoma is a rare but highly malignant cancer of the bone. As a
      consequence, the number of established cell lines used for experimental in vitro
      and in vivo osteosarcoma research is limited and the value of these cell lines
      relies on their stability during culture. Here we investigated the stability in
      gene expression by microarray analysis and array genomic hybridization of three
      low metastatic cell lines and derivatives thereof with increased metastatic
      potential using cells of different passages. PRINCIPAL FINDINGS: The osteosarcoma
      cell lines showed altered gene expression during in vitro culture, and it was
      more pronounced in two metastatic cell lines compared to the respective parental
      cells. Chromosomal instability contributed in part to the altered gene expression
      in SAOS and LM5 cells with low and high metastatic potential. To identify
      metastasis-relevant genes in a background of passage-dependent altered gene
      expression, genes involved in "Pathways in cancer" that were consistently
      regulated under all passage comparisons were evaluated. Genes belonging to
      "Hedgehog signaling pathway" and "Wnt signaling pathway" were significantly up
      regulated, and IHH, WNT10B and TCF7 were found up-regulated in all three
      metastatic compared to the parental cell lines. CONCLUSIONS: Considerable
      instability during culture in terms of gene expression and chromosomal
      aberrations was observed in osteosarcoma cell lines. The use of cells from
      different passages and a search for genes consistently regulated in early and
      late passages allows the analysis of metastasis-relevant genes despite the
      observed instability in gene expression in osteosarcoma cell lines during
      culture.

PMID- 25992887
TI  - Public Opinions about Overdiagnosis: A National Community Survey.
AB  - BACKGROUND: Despite evidence about the "modern epidemic" of overdiagnosis, and
      expanding disease definitions that medicalize more people, data are lacking on
      public views about these issues. Our objective was to measure public perceptions
      about overdiagnosis and views about financial ties of panels setting disease
      definitions. METHODS: We conducted a 15 minute Computer Assisted Telephone
      Interview with a randomly selected community sample of 500 Australians in January
      2014. We iteratively developed and piloted a questionnaire, with a convenience
      sample (n=20), then with participants recruited by a research company (n=20).
      Questions included whether respondents had been informed about overdiagnosis;
      opinions on informing people; and views about financial ties among panels writing
      disease definitions. FINDINGS: Our sample was generally representative, but
      included a higher proportion of females and seniors, typical of similar surveys.
      American Association for Public Opinion Research response rate was 20% and
      cooperation rate was 44%. Only 10% (95% CI 8%-13%) of people reported ever being
      told about overdiagnosis by a doctor. 18% (95% CI 11%-28%) of men who reported
      having prostate cancer screening, and 10% (95% CI 6%-15%) of women who reported
      having mammography said they were told about overdiagnosis. 93% (95% CI 90%-95%)
      agreed along with screening benefits, people should be informed about
      overdiagnosis. On panels setting disease definitions, 78% (95% CI 74%-82%) felt
      ties to pharmaceutical companies inappropriate, and 91% (95% CI 82%-100%)
      believed panels should have a minority or no members with ties. Limitations
      included questionnaire novelty and complexity. CONCLUSIONS: A small minority of
      Australians surveyed, including those reporting being screened for prostate or
      breast cancer, reported being informed of overdiagnosis; most believed people
      should be informed; and a majority felt it inappropriate that doctors with ties
      to pharmaceutical companies write disease definitions. Results suggest strategies
      to better inform people about overdiagnosis, and review disease definition
      processes, have significant public sympathy.

PMID- 25992889
TI  - Erratum: Mouthrinse recommendation for prosthodontic patients.

PMID- 25992891
TI  - Erratum: Antimicrobial mouthrinse use as an adjunct method in peri-implant
      biofilm control.

PMID- 25992888
TI  - Somatic antigens of tropical liver flukes ameliorate collagen-induced arthritis
      in wistar rats.
AB  - Parasitic helminths polarize immune response of their vertebrate hosts towards
      anti-inflammatory Th2 type and therefore it is hypothesized that they may
      suppress the inflammatory conditions in autoimmune disorders. The present study
      was undertaken to investigate in vivo immunomodulatory and therapeutic potential
      of somatic antigens (Ag) of liver infecting digenetic trematodes [Fasciola
      gigantica (Fg) and Gigantocotyle explanatum (Ge)] in collagen-induced arthritic
      (CIA) Wistar rats. The CIA rats were administered subcutaneously with different
      doses (50 MUg, 100 MUg and 150 MUg) of somatic antigens of Fg and Ge, daily for
      21 days, the time period required to establish infection in natural host (Bubalus
      bubalis). Thereafter, the control, diseased and treated rats were compared for
      different parameters viz. hind paw thickness; serum interleukins, IL-4 and IL-10,
      tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma);
      expression level of matrix metalloproteinases (MMPs) -2, -9, -13 and nitric oxide
      (NO) in knee joints and patellar morphology. The CIA rats treated with different
      antigens, Fg-Ag and Ge-Ag, show significant amelioration of the disease by down
      regulation of serum TNF-alpha and IFN-gamma (p< 0.05) and upregulation of IL-4
      and IL-10 cytokines (p< 0.05); inhibition (p< 0.05) of MMPs (-2,-9,-13) and NO in
      knee joints and improved patellar morphology with decreased synovial hypertrophy
      and reduced infiltration of ploymorphonuclear cells. The activity of pro as well
      as active MMPs (-2 and -9) and active MMP-13 in knee joints of CIA rats was very
      high compared to the control and treatment groups, suggesting the extent of
      collagen degradation in CIA rats. Interestingly, the highest dose (150 MUg) of Ge
      Ag almost wiped out MMP-13 expression. The overall findings suggest that the
      somatic proteins of Ge-Ag appeared to be therapeutically more effective than Fg
      Ag, reflecting interspecific molecular differences which could contribute to the
      ability of these worms to successfully ameliorate the pathology of CIA. 

PMID- 25992892
TI  - Spatial analysis of childhood cancer: a case/control study.
AB  - BACKGROUND: Childhood cancer was the leading cause of death among children aged 1
      14 years for 2012 in Spain. Leukemia has the highest incidence, followed by
      tumors of the central nervous system (CNS) and lymphomas (Hodgkin lymphoma, HL,
      and Non-Hodgkin's lymphoma, NHL). Spatial distribution of childhood cancer cases
      has been under concern with the aim of identifying potential risk factors.
      OBJECTIVE: The two objectives are to study overall spatial clustering and cluster
      detection of cases of the three main childhood cancer causes, looking to increase
      etiological knowledge. METHODS: We ran a case-control study. The cases were
      children aged 0 to 14 diagnosed with leukemia, lymphomas (HL and NHL) or CNS
      neoplasm in five Spanish regions for the period 1996-2011. As a control group, we
      used a sample from the Birth Registry matching every case by year of birth,
      autonomous region of residence and sex with six controls. We geocoded and
      validated the address of the cases and controls. For our two objectives we used
      two different methodologies. For the first, for overall spatial clustering
      detection, we used the differences of K functions from the spatial point patterns
      perspective proposed by Diggle and Chetwynd and the second, for cluster
      detection, we used the spatial scan statistic proposed by Kulldorff with a level
      for statistical significance of 0.05. RESULTS: We had 1062 cases of leukemia, 714
      cases of CNS, 92 of HL and 246 of NHL. Accordingly we had 6 times the number of
      controls, 6372 controls for leukemia, 4284 controls for CNS, 552 controls for HL
      and 1476 controls for NHL. We found variations in the estimated empirical D(s)
      for the different regions and cancers, including some overall spatial clustering
      for specific regions and distances. We did not find statistically significant
      clusters. CONCLUSIONS: The variations in the estimated empirical D(s) for the
      different regions and cancers could be partially explained by the differences in
      the spatial distribution of the population; however, according to the literature,
      we cannot discard environmental hazards or infections agents in the etiology of
      these cancers.

PMID- 25992893
TI  - Structure-Based Alignment and Consensus Secondary Structures for Three HIV
      Related RNA Genomes.
AB  - HIV and related primate lentiviruses possess single-stranded RNA genomes.
      Multiple regions of these genomes participate in critical steps in the viral
      replication cycle, and the functions of many RNA elements are dependent on the
      formation of defined structures. The structures of these elements are still not
      fully understood, and additional functional elements likely exist that have not
      been identified. In this work, we compared three full-length HIV-related viral
      genomes: HIV-1NL4-3, SIVcpz, and SIVmac (the latter two strains are progenitors
      for all HIV-1 and HIV-2 strains, respectively). Model-free RNA structure
      comparisons were performed using whole-genome structure information
      experimentally derived from nucleotide-resolution SHAPE reactivities. Consensus
      secondary structures were constructed for strongly correlated regions by taking
      into account both SHAPE probing structural data and nucleotide covariation
      information from structure-based alignments. In these consensus models, all known
      functional RNA elements were recapitulated with high accuracy. In addition, we
      identified multiple previously unannotated structural elements in the HIV-1
      genome likely to function in translation, splicing and other replication cycle
      processes; these are compelling targets for future functional analyses. The
      structure-informed alignment strategy developed here will be broadly useful for
      efficient RNA motif discovery. 

PMID- 25992894
TI  - New absorbed dose measurement with cylindrical water phantoms for multidetector
      CT.
AB  - The aim of this study was to develop new dosimetry with cylindrical water
      phantoms for multidetector computed tomography (MDCT). The ionization measurement
      was performed with a Farmer ionization chamber at the center and four peripheral
      points in the body-type and head-type cylindrical water phantoms. The ionization
      was converted to the absorbed dose using a (60)Co absorbed-dose-to-water
      calibration factor and Monte Carlo (MC) -calculated correction factors. The
      correction factors were calculated from MDCT (Brilliance iCT, 64-slice, Philips
      Electronics) modeled with GMctdospp (IMPS, Germany) software based on the EGSnrc
      MC code. The spectrum of incident x-ray beams and the configuration of a bowtie
      filter for MDCT were determined so that calculated photon intensity attenuation
      curves for aluminum (Al) and calculated off-center ratio (OCR) profiles in air
      coincided with those measured. The MC-calculated doses were calibrated by the
      absorbed dose measured at the center in both cylindrical water phantoms.
      Calculated doses were compared with measured doses at four peripheral points and
      the center in the phantom for various beam pitches and beam collimations. The
      calibration factors and the uncertainty of the absorbed dose determined using
      this method were also compared with those obtained by CTDIair (CT dose index in
      air). Calculated Al half-value layers and OCRs in air were within 0.3% and 3%
      agreement with the measured values, respectively. Calculated doses at four
      peripheral points and the centers for various beam pitches and beam collimations
      were within 5% and 2% agreement with measured values, respectively. The MC
      calibration factors by our method were 44-50% lower than values by CTDIair due to
      the overbeaming effect. However, the calibration factors for CTDIair agreed
      within 5% with those of our method after correction for the overbeaming effect.
      Our method makes it possible to directly measure the absorbed dose for MDCT and
      is more robust and accurate than the CTDIair measurement.

PMID- 25992895
TI  - The health system and population health implications of large-scale diabetes
      screening in India: a microsimulation model of alternative approaches.
AB  - BACKGROUND: Like a growing number of rapidly developing countries, India has
      begun to develop a system for large-scale community-based screening for diabetes.
      We sought to identify the implications of using alternative screening instruments
      to detect people with undiagnosed type 2 diabetes among diverse populations
      across India. METHODS AND FINDINGS: We developed and validated a microsimulation
      model that incorporated data from 58 studies from across the country into a
      nationally representative sample of Indians aged 25-65 y old. We estimated the
      diagnostic and health system implications of three major survey-based screening
      instruments and random glucometer-based screening. Of the 567 million Indians
      eligible for screening, depending on which of four screening approaches is
      utilized, between 158 and 306 million would be expected to screen as "high risk"
      for type 2 diabetes, and be referred for confirmatory testing. Between 26 million
      and 37 million of these people would be expected to meet international diagnostic
      criteria for diabetes, but between 126 million and 273 million would be "false
      positives." The ratio of false positives to true positives varied from 3.9 (when
      using random glucose screening) to 8.2 (when using a survey-based screening
      instrument) in our model. The cost per case found would be expected to be from
      US$5.28 (when using random glucose screening) to US$17.06 (when using a survey
      based screening instrument), presenting a total cost of between US$169 and US$567
      million. The major limitation of our analysis is its dependence on published
      cohort studies that are unlikely fully to capture the poorest and most rural
      areas of the country. Because these areas are thought to have the lowest diabetes
      prevalence, this may result in overestimation of the efficacy and health benefits
      of screening. CONCLUSIONS: Large-scale community-based screening is anticipated
      to produce a large number of false-positive results, particularly if using
      currently available survey-based screening instruments. Resource allocators
      should consider the health system burden of screening and confirmatory testing
      when instituting large-scale community-based screening for diabetes.

PMID- 25992896
TI  - Hemodilution on cardiopulmonary bypass as a determinant of early postoperative
      hyperlactatemia.
AB  - OBJECTIVE: The nadir hematocrit (HCT) on cardiopulmonary bypass (CPB) is a
      recognized independent risk factor for major morbidity and mortality in cardiac
      surgery. The main interpretation is that low levels of HCT on CPB result in a
      poor oxygen delivery and dysoxia of end organs. Hyperlactatemia (HL) is a marker
      of dysoxic metabolism, and is associated with bad outcomes in cardiac surgery.
      This study explores the relationship between nadir HCT on CPB and early
      postoperative HL. DESIGN: Retrospective study on 3,851 consecutive patients.
      MEASUREMENTS AND MAIN RESULTS: Nadir HCT on CPB and other potential confounders
      were explored for association with blood lactate levels at the arrival in the
      Intensive Care Unit (ICU), and with the presence of moderate (2.1 - 6.0 mMol/L)
      or severe (> 6.0 mMol/L) HL. Nadir HCT on CPB demonstrated a significant negative
      association with blood lactate levels at the arrival in the ICU. After adjustment
      for the other confounders, the nadir HCT on CPB remained independently associated
      with moderate (odds ratio 0.96, 95% confidence interval 0.94-0.99) and severe HL
      (odds ratio 0.91, 95% confidence interval 0.86-0.97). Moderate and severe HL were
      significantly associated with increased morbidity and mortality. CONCLUSIONS:
      Hemodilution on CPB is an independent determinant of HL. This association, more
      evident for severe HL, strengthens the hypothesis that a poor oxygen delivery on
      CPB with consequent organ ischemia is the mechanism leading to hemodilution
      associated bad outcomes.

PMID- 25992898
TI  - Perception and regulatory principles of microbial growth control.
AB  - Fast growth represents an effective strategy for microbial organisms to survive
      in competitive environments. To accomplish this task, cells must adapt their
      metabolism to changing nutrient conditions in a way that maximizes their growth
      rate. However, the regulation of the growth related metabolic pathways can be
      fundamentally different among microbes. We therefore asked whether growth control
      by perception of the cell's intracellular metabolic state can give rise to higher
      growth than by direct perception of extracellular nutrient availability. To
      answer this question, we created a simplified dynamical computer model of a
      cellular metabolic network whose regulation was inferred by an optimization
      approach. We used this model for a competing species experiment, where a species
      with extracellular nutrient perception competes against one with intracellular
      nutrient perception by evaluating their respective average growth rate. We found
      that the intracellular perception is advantageous under situations where the up
      and down regulation of pathways cannot follow the fast changing nutrient
      availability in the environment. In this case, optimal regulation ignores any
      other nutrients except the most preferential ones, in agreement with the
      phenomenon of catabolite repression in prokaryotes. The corresponding metabolic
      pathways remain activated, despite environmental fluctuations. Therefore, the
      cell can take up preferential nutrients as soon as they are available without any
      prior regulation. As a result species that rely on intracellular perception gain
      a relevant fitness advantage in fluctuating nutrient environments, which enables
      survival by outgrowing competitors. 

PMID- 25992897
TI  - Characterization of the Two CART Genes (CART1 and CART2) in Chickens (Gallus
      gallus).
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptide is implicated in the
      control of avian energy balance, however, the structure and expression of CART
      gene(s) remains largely unknown in birds. Here, we cloned and characterized two
      CART genes (named cCART1 and cCART2) in chickens. The cloned cCART1 is predicted
      to generate two bioactive peptides, cCART1(42-89) and cCART1(49-89), which share
      high amino acid sequence identity (94-98%) with their mammalian counterparts,
      while the novel cCART2 may produce a bioactive peptide cCART2(51-91) with 59%
      identity to cCART1. Interestingly, quantitative RT-PCR revealed that cCART1 is
      predominantly expressed in the anterior pituitary and less abundantly in the
      hypothalamus. In accordance with this finding, cCART1 peptide was easily detected
      in the anterior pituitary by Western blot, and its secretion from chick
      pituitaries incubated in vitro was enhanced by ionomycin and forskolin treatment,
      indicating that cCART1 is a novel peptide hormone produced by the anterior
      pituitary. Moreover, cCART1 mRNA expression in both the pituitary and
      hypothalamus is down-regulated by 48-h fasting, suggesting its expression is
      affected by energy status. Unlike cCART1, cCART2 is only weakly expressed in most
      tissues examined by RT-PCR, implying a less significant role of cCART2 in
      chickens. As in chickens, 2 or more CART genes, likely generated by gene and
      genome duplication event(s), were also identified in other non-mammalian
      vertebrate species including coelacanth. Collectively, the identification and
      characterization of CART genes in birds helps to uncover the roles of CART
      peptide(s) in vertebrates and provides clues to the evolutionary history of
      vertebrate CART genes. 

PMID- 25992899
TI  - Interval timing deficits assessed by time reproduction dual tasks as cognitive
      endophenotypes for attention-deficit/hyperactivity disorder.
AB  - The literature has suggested timing processing as a potential endophenotype for
      attention deficit/hyperactivity disorder (ADHD); however, whether the subjective
      internal clock speed presented by verbal estimation and limited attention
      capacity presented by time reproduction could be endophenotypes for ADHD is still
      unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105
      unaffected siblings, and 84 typically developing (TD) youths using psychiatric
      interviews, intelligence tests, verbal estimation and time reproduction tasks
      (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17
      second intervals. We found that youths with ADHD tended to overestimate time in
      verbal estimation more than their unaffected siblings and TD youths, implying
      that fast subjective internal clock speed might be a characteristic of ADHD,
      rather than an endophenotype for ADHD. Youths with ADHD and their unaffected
      siblings were less precise in time reproduction dual tasks than TD youths. The
      magnitude of estimated errors in time reproduction was greater in youths with
      ADHD and their unaffected siblings than in TD youths, with an increased time
      interval at the 17-second interval and with increased task demands on both simple
      and difficult dual tasks versus the single task. Increased impaired time
      reproduction in dual tasks with increased intervals and task demands were shown
      in youths with ADHD and their unaffected siblings, suggesting that time
      reproduction deficits explained by limited attention capacity might be a useful
      endophenotype of ADHD. 

PMID- 25992901
TI  - Use of Contraception and Attitudes towards Contraceptive Use in Swedish Women--A
      Nationwide Survey.
AB  - OBJECTIVE: To describe contraceptive use and attitudes towards contraceptive use
      in Sweden which has the highest abortion rate in Western Europe. Secondary
      objectives were to investigate knowledge of contraceptive methods and outcomes of
      unplanned and unwanted pregnancies. DESIGN: Telephone survey. SETTING: National
      survey of women living in Sweden. POPULATION: Women between 16 and 49 years.
      METHODS: The survey contained 22 questions with free text and multi choice
      answers on demographics, contraceptive use, knowledge of and attitudes towards
      contraception, the importance of monthly bleeding and experience of unintended
      pregnancy. MAIN OUTCOME MEASURES: Distribution of use of contraceptive methods
      and non-use of contraception among Swedish women. Prevalence and outcome of
      unintended pregnancies. RESULTS: A total of 1001 women participated in the
      survey. Of all women, 721/1001 (72.1%) currently used contraception whereas
      268/1001 (26.8%) women did not. Long acting reversible contraception, (LARC;
      implant and intra uterine contraception) was used by 24.3% of women. The unmet
      need of contraception in Sweden was estimated at 8.9% (89/1001 women). A total of
      781 (78%) women had never experienced an unintended pregnancy whereas 220 (22%)
      women had had at least one unintended pregnancy. Users and non-users alike stated
      that one of the most important characteristics of a contraceptive method is its
      effectiveness. CONCLUSIONS: Sweden has a large unmet need for contraception.
      Furthermore, a large proportion of women have experienced at least one unintended
      pregnancy. Increasing contraceptive use and promotion of LARC is a possible way
      forward in the effort to reduce the rates of unwanted pregnancies.

PMID- 25992902
TI  - Constrained Optimization of Average Arrival Time via a Probabilistic Approach to
      Transport Reliability.
AB  - To achieve greater transit-time reduction and improvement in reliability of
      transport services, there is an increasing need to assist transport planners in
      understanding the value of punctuality; i.e. the potential improvements, not only
      to service quality and the consumer but also to the actual profitability of the
      service. In order for this to be achieved, it is important to understand the
      network-specific aspects that affect both the ability to decrease transit-time,
      and the associated cost-benefit of doing so. In this paper, we outline a
      framework for evaluating the effectiveness of proposed changes to average transit
      time, so as to determine the optimal choice of average arrival time subject to
      desired punctuality levels whilst simultaneously minimizing operational costs. We
      model the service transit-time variability using a truncated probability density
      function, and simultaneously compare the trade-off between potential gains and
      increased service costs, for several commonly employed cost-benefit functions of
      general form. We formulate this problem as a constrained optimization problem to
      determine the optimal choice of average transit time, so as to increase the level
      of service punctuality, whilst simultaneously ensuring a minimum level of cost
      benefit to the service operator. 

PMID- 25992900
TI  - Roles of Prolyl Isomerases in RNA-Mediated Gene Expression.
AB  - The peptidyl-prolyl cis-trans isomerases (PPIases) that include immunophilins
      (cyclophilins and FKBPs) and parvulins (Pin1, Par14, Par17) participate in cell
      signaling, transcription, pre-mRNA processing and mRNA decay. The human genome
      encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are
      receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin
      that are used in organ transplantation. Pin1 has also been targeted in the
      treatment of Alzheimer's disease, asthma, and a number of cancers. While these
      PPIases are characterized as molecular chaperones, they also act in a
      nonchaperone manner to promote protein-protein interactions using surfaces
      outside their active sites. The immunosuppressive drugs act by a gain-of-function
      mechanism by promoting protein-protein interactions in vivo. Several
      immunophilins have been identified as components of the spliceosome and are
      essential for alternative splicing. Pin1 plays roles in transcription and RNA
      processing by catalyzing conformational changes in the RNA Pol II C-terminal
      domain. Pin1 also binds several RNA binding proteins such as AUF1, KSRP, HuR, and
      SLBP that regulate mRNA decay by remodeling mRNP complexes. The functions of
      ribonucleoprotein associated PPIases are largely unknown. This review highlights
      PPIases that play roles in RNA-mediated gene expression, providing insight into
      their structures, functions and mechanisms of action in mRNP remodeling in vivo. 

PMID- 25992903
TI  - Fast, Efficient, and Stable Conjugation of Multiple DNA Strands on Colloidal
      Quantum Dots.
AB  - A novel method for covalent conjugation of DNA to polymer coated quantum dots
      (QDs) is investigated in detail. This method is fast and efficient: up to 12 DNA
      strands can be covalently conjugated per QD in optimized reaction conditions. The
      QD-DNA conjugates can be purified using size exclusion chromatography and the QDs
      retain high quantum yield and excellent stability after DNA coupling. We explored
      single-stranded and double-stranded DNA coupling, as well as various lengths. We
      show that the DNA coupling is most efficient for short (15 mer) single-stranded
      DNA. The DNA coupling has been performed on QDs emitting at four different
      wavelengths, as well as on gold nanoparticles, suggesting that this technique can
      be generalized to a wide range of nanoparticles. 

PMID- 25992905
TI  - Carbon Sequestration of Caesalpinia platyloba S. Watt (Leguminosae) (Lott 1985)
      in the Tropical Deciduous Forest.
AB  - Caesalpinia platyloba was evaluated as an alternative for the retention of
      atmospheric carbon and as a feasible and viable economic activity in terms of
      income for tropical deciduous forest (TDF) peasants in the carbon markets. A
      total of 110 trees of C. platyloba from plantations and a TDF in the Northwest of
      Mexico were sampled. Growth (increase in height, diameter, and volume curves) was
      adjusted to assess their growth. Growth of individuals (height, diameter at
      breast height [DBH], age, and tree crown cover) was recorded. The Schumacher
      model (H = beta(0)e(beta1 * E-1)), by means of the guided curve method, was used
      to adjust growth models. Information analysis was made through the non-linear
      procedure with the multivariate secant or false position (DUD) method using the
      SAS software. Growth and increase models revealed acceptable adjustments (pseudo
      R(2)>0.8). C. platyloba reaches >8m of height with 12 cm in diameter and 550
      cm(3) of volume, presenting the highest increase at 11 years considered as basal
      age. Highest significant density of wood was in good quality sites (0.80 g * cm(
      3)), with a carbon content (average of 99.15tC * ha(-1)) at the highest density
      of 2500 trees * ha(-1) (without thinning). Average incomes of US$483.33tC * ha(
      1) are expected. The profitability values (NPW = US$81,646.65, IRR = 472%, and
      B/C = 0.82) for C. platyloba make its cultivation a viable and profitable
      activity, considering a management scheme of the income derived from wood selling
      and from carbon credits.

PMID- 25992906
TI  - Correction: Chinese Social Media Reaction to Information about 42 Notifiable
      Infectious Diseases.

PMID- 25992907
TI  - Identification of controlling factors for the initiation of corrosion of fresh
      concrete sewers.
AB  - The development of concrete corrosion in new sewer pipes undergoes an initiation
      process before reaching an active corrosion stage. This initiation period is
      assumed to last several months to years but the key factors affecting the
      process, and its duration, are not well understood. This study is therefore
      focused on this initial stage of the corrosion process and the effect of key
      environmental factors. Such knowledge is important for the effective management
      of corrosion in new sewers, as every year of life extension of such systems has a
      very high financial benefit. This long-term (4.5 year) study has been conducted
      in purpose-built corrosion chambers that closely simulated the sewer environment,
      but with control of three key environmental factors being hydrogen sulfide (H2S)
      gas phase concentration, relative humidity and air temperature. Fresh concrete
      coupons, cut from an industry-standard sewer pipe, were exposed to the corrosive
      conditions in the chambers, both in the gas phase and partially submerged in
      wastewater. A total of 36 exposure conditions were investigated to determine the
      controlling factors by regular retrieval of concrete coupons for detailed
      analysis of surface pH, sulfur compounds (elemental sulfur and sulfate) and
      concrete mass loss. Corrosion initiation times were thus determined for different
      exposure conditions. It was found that the corrosion initiation time of both gas
      phase and partially-submerged coupons was positively correlated with the gas
      phase H2S concentration, but only at levels of 10 ppm or below, indicating that
      sulfide oxidation rate rather than the H2S concentration was the limiting factor
      during the initiation stage. Relative humidity also played a role for the
      corrosion initiation of the gas-phase coupons. However, the partially-submerged
      coupons were not affected by humidity as these coupons were in direct contact
      with the sewage and hence did have sufficient moisture to enable the microbial
      processes to proceed. The corrosion initiation time was also shortened by higher
      gas temperature due to its positive impact on reaction kinetics. These findings
      provide real opportunities for pro-active sewer asset management with the aim to
      delay the on-set of the corrosion processes, and hence extend the service life of
      sewers, through improved prediction and optimization capacity.

PMID- 25992909
TI  - Amphibious shelter-builder Oniscidea species from the New World with description
      of a new subfamily, a new genus and a new species from Brazilian cave (Isopoda,
      Synocheta, Styloniscidae).
AB  - The new subfamily Iuiuniscinae, Styloniscidae, is erected for the new genus
      Iuiuniscus and the new species I. iuiuensis, which is described from cave of the
      State of Bahia, Northeastern Brazil. A special ecological character is shown here
      for the first time for a New World Oniscidea: the construction of mud shelters.
      An introduction addressing the systematics of Synocheta with emphasis on
      Styloniscidae Vandel, 1952 is provided, as well as general comments about the
      dependence of water in some Oniscidea and ecological traits of amphibious
      Synocheta. The problems referring to nomenclature, taxonomy and the
      interrelationships in Styloniscidae are discussed. 

PMID- 25992908
TI  - Describing directional cell migration with a characteristic directionality time.
AB  - Many cell types can bias their direction of locomotion by coupling to external
      cues. Characteristics such as how fast a cell migrates and the directedness of
      its migration path can be quantified to provide metrics that determine which
      biochemical and biomechanical factors affect directional cell migration, and by
      how much. To be useful, these metrics must be reproducible from one experimental
      setting to another. However, most are not reproducible because their numerical
      values depend on technical parameters like sampling interval and measurement
      error. To address the need for a reproducible metric, we analytically derive a
      metric called directionality time, the minimum observation time required to
      identify motion as directionally biased. We show that the corresponding fit
      function is applicable to a variety of ergodic, directionally biased motions. A
      motion is ergodic when the underlying dynamical properties such as speed or
      directional bias do not change over time. Measuring the directionality of
      nonergodic motion is less straightforward but we also show how this class of
      motion can be analyzed. Simulations are used to show the robustness of
      directionality time measurements and its decoupling from measurement errors. As a
      practical example, we demonstrate the measurement of directionality time, step-by
      step, on noisy, nonergodic trajectories of chemotactic neutrophils. Because of
      its inherent generality, directionality time ought to be useful for
      characterizing a broad range of motions including intracellular transport, cell
      motility, and animal migration. 

PMID- 25992910
TI  - Metallic WO2-Carbon Mesoporous Nanowires as Highly Efficient Electrocatalysts for
      Hydrogen Evolution Reaction.
AB  - The development of electrocatalysts to generate hydrogen, with good activity and
      stability, is a great challenge in the fields of chemistry and energy. Here we
      demonstrate a "hitting three birds with one stone" method to synthesize less
      toxic metallic WO2-carbon mesoporous nanowires with high concentration of oxygen
      vacancies (OVs) via calcination of inorganic/organic WO3-ethylenediamine hybrid
      precursors. The products exhibit excellent performance for H2 generation: the
      onset overpotential is only 35 mV, the required overpotentials for 10 and 20
      mA/cm(2) are 58 and 78 mV, the Tafel slope is 46 mV/decade, the exchange current
      density is 0.64 mA/cm(2), and the stability is over 10 h. Further studies, in
      combination with density functional theory, demonstrate that the unusual
      electronic structure and the large amount of active sites, generated by the high
      concentration of OVs, as well as the closely attached carbon materials, were key
      factors for excellent performance. Our results experimentally and theoretically
      establish metallic transition metal oxides (TMOs) as intriguing novel
      electrocatalysts for H2 generation. Such TMOs with OVs might be promising
      candidates for other energy storage and conversion applications. 

PMID- 25992912
TI  - Vibronic Coupling Investigation to Compute Phosphorescence Spectra of Pt(II)
      Complexes.
AB  - The present paper reports a comprehensive quantum mechanical investigation on the
      luminescence properties of several mono- and dinuclear platinum(II) complexes.
      The electronic structures and geometric parameters are briefly analyzed together
      with the absorption bands of all complexes. In all cases agreement with
      experiment is remarkable. Next, emission (phosphorescence) spectra from the first
      triplet states have been investigated by comparing different computational
      approaches and taking into account also vibronic effects. Once again, agreement
      with experiment is good, especially using unrestricted electronic computations
      coupled to vibronic contributions. Together with the intrinsic interest of the
      results, the robustness and generality of the approach open the opportunity for
      computationally oriented chemists to provide accurate results for the screening
      of large targets which could be of interest in molecular materials design. 

PMID- 25992913
TI  - Distributed clone detection in static wireless sensor networks: random walk with
      network division.
AB  - Wireless Sensor Networks (WSNs) are vulnerable to clone attacks or node
      replication attacks as they are deployed in hostile and unattended environments
      where they are deprived of physical protection, lacking physical tamper
      resistance of sensor nodes. As a result, an adversary can easily capture and
      compromise sensor nodes and after replicating them, he inserts arbitrary number
      of clones/replicas into the network. If these clones are not efficiently
      detected, an adversary can be further capable to mount a wide variety of internal
      attacks which can emasculate the various protocols and sensor applications.
      Several solutions have been proposed in the literature to address the crucial
      problem of clone detection, which are not satisfactory as they suffer from some
      serious drawbacks. In this paper we propose a novel distributed solution called
      Random Walk with Network Division (RWND) for the detection of node replication
      attack in static WSNs which is based on claimer-reporter-witness framework and
      combines a simple random walk with network division. RWND detects clone(s) by
      following a claimer-reporter-witness framework and a random walk is employed
      within each area for the selection of witness nodes. Splitting the network into
      levels and areas makes clone detection more efficient and the high security of
      witness nodes is ensured with moderate communication and memory overheads. Our
      simulation results show that RWND outperforms the existing witness node based
      strategies with moderate communication and memory overheads. 

PMID- 25992911
TI  - Intestinal microbiota and its relationship with necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in
      infants born prematurely. After birth, the neonatal gut must acquire a healthy
      complement of commensal bacteria. Disruption or delay of this critical process,
      leading to deficient or abnormal microbial colonization of the gut, has been
      implicated as key risk factor in the pathogenesis of NEC. Conversely, a
      beneficial complement of commensal intestinal microbiota may protect the immature
      gut from inflammation and injury. Interventions aimed at providing or restoring a
      healthy complement of commensal bacteria, such as probiotic therapy, are
      currently the most promising treatment to prevent NEC. Shifting the balance of
      intestinal microbiota from a pathogenic to protective complement of bacteria can
      protect the gut from inflammation and subsequent injury that leads to NEC.
      Herein, we review the relationship of intestinal microbiota and NEC in preterm
      infants. 

PMID- 25992914
TI  - Predicted vs. observed radiographic progression in early rheumatoid arthritis
      (POPeRA): results from a randomized trial.
AB  - OBJECTIVES: The aim of this study was to apply a previously published method for
      evaluating radiographic progression, namely, predicted vs. observed radiographic
      progression in early rheumatoid arthritis (POPeRA), to the Swedish
      pharmacotherapy (SWEFOT) trial. METHOD: In SWEFOT, 487 patients with eRA were
      given methotrexate (MTX), and non-responders were randomized to group A [triple
      therapy: MTX+sulfasalazine (SSZ)+hydroxychloroquine (HCQ)] and group B [anti
      tumour necrosis factor (anti-TNF) therapy: MTX+infliximab]. Responders continued
      on MTX. Predicted progression for 343 eligible patients was calculated based on
      the baseline total Sharp/van der Heijde score (SHS) divided by symptom duration,
      compared to observed progression at 12 and 24 months. RESULTS: Observed
      radiographic progression was reduced from predicted by a mean of 50.1% (A), 72.3%
      (B), and 73.9% (MTX) at 12 months and by 87.2, 89.8, and 87.8% at 24 months,
      respectively. Among completers, reductions of 56.7% (A) and 76.5% (B) at 12
      months and of 91.0% and 96.0% at 24 months, respectively, were observed. At 12
      months, there were no significant between-group differences. At 24 months,
      progression was reduced more in group B than in group A (first quartile
      difference 8.5% favouring group B) and in MTX [n=316, 89.8% (sd+/-32.0) vs. 87.2%
      (+/-32.2), p=0.021; vs. 87.8% (+/-27.8), p=0.013, respectively]. CONCLUSIONS: The
      POPeRA method confirms the original SWEFOT finding in that anti-TNF therapy was
      statistically marginally superior (2.6%) to triple therapy in preventing
      radiographic progression at 24 months among initial MTX non-responders. The
      simulation provided through POPeRA may facilitate comparisons of the relative
      efficacy of various treatments in preventing radiographic progression.

PMID- 25992916
TI  - Origin of enhanced visible light driven water splitting by (Rh, Sb)-SrTiO3.
AB  - A systematic calculation, using hybrid density functional theory, has been
      carried out to investigate the origin of the enhancement of photo-conversion
      efficiency of Rh-doped SrTiO3 with codoping of Sb. In the case of Rh-doped
      SrTiO3, partially unoccupied states are introduced above the valence band, thus
      lowering the hole oxidation at the valence band (VB) drastically, which explains
      the poor oxygen evolution activity of Rh-doped SrTiO3. We show that the partially
      occupied t2g subset of the Rh 4d orbital is completely filled in the presence of
      Sb due to the transfer of the extra electron to the Rh center. As a result,
      acceptor states are completely passivated in the case of (Rh, Sb)-codoped SrTiO3
      and a continuous band structure with reduced band gap is formed, which is
      responsible for the observed enhanced photocatalytic activity of (Rh, Sb)-codoped
      SrTiO3. We have shown that the relative positions of the band edges of (Rh, Sb)
      codoped SrTiO3 with respect to the water redox levels are in favor of the
      spontaneous release of both hydrogen and oxygen during water splitting, which is
      consistent with the experimental observation. We have also studied the effect of
      codoping in different proportions (1 : 2 and 2 : 1) of Rh and Sb. Although 1 : 2
      (Rh, Sb)-codoping leads to the formation of a clean band structure with the
      reduction of the band gap by a larger extent, it shows lower photo-conversion
      efficiency due to its charge non-compensated nature. In addition, the presence of
      acceptor states above the VB limits the oxygen evolution efficiency of 2 : 1 (Rh,
      Sb)-codoped SrTiO3. Thus, the present approach successfully reproduces the
      experimental features of the Rh-monodoped as well as (Rh, Sb)-codoped SrTiO3 and
      also explains their origin. 

PMID- 25992915
TI  - Quantitative localization microscopy: effects of photophysics and labeling
      stoichiometry.
AB  - Quantification in localization microscopy with reversibly switchable fluorophores
      is severely hampered by the unknown number of switching cycles a fluorophore
      undergoes and the unknown stoichiometry of fluorophores on a marker such as an
      antibody. We overcome this problem by measuring the average number of
      localizations per fluorophore, or generally per fluorescently labeled site from
      the build-up of spatial image correlation during acquisition. To this end we
      employ a model for the interplay between the statistics of activation, bleaching,
      and labeling stoichiometry. We validated our method using single fluorophore
      labeled DNA oligomers and multiple-labeled neutravidin tetramers where we find a
      counting error of less than 17% without any calibration of transition rates.
      Furthermore, we demonstrated our quantification method on nanobody- and antibody
      labeled biological specimens. 

PMID- 25992917
TI  - Immunohistochemical visualization of hippocampal neuron activity after spatial
      learning in a mouse model of neurodevelopmental disorders.
AB  - Induction of phosphorylated extracellular-regulated kinase (pERK) is a reliable
      molecular readout of learning-dependent neuronal activation. Here, we describe a
      pERK immunohistochemistry protocol to study the profile of hippocampal neuron
      activation following exposure to a spatial learning task in a mouse model
      characterized by cognitive deficits of neurodevelopmental origin. Specifically,
      we used pERK immunostaining to study neuronal activation following Morris water
      maze (MWM, a classical hippocampal-dependent learning task) in Engrailed-2
      knockout (En2(-/-)) mice, a model of autism spectrum disorders (ASD). As compared
      to wild-type (WT) controls, En2(-/-) mice showed significant spatial learning
      deficits in the MWM. After MWM, significant differences in the number of pERK
      positive neurons were detected in specific hippocampal subfields of En2(-/-)
      mice, as compared to WT animals. Thus, our protocol can robustly detect
      differences in pERK-positive neurons associated to hippocampal-dependent learning
      impairment in a mouse model of ASD. More generally, our protocol can be applied
      to investigate the profile of hippocampal neuron activation in both genetic or
      pharmacological mouse models characterized by cognitive deficits. 

PMID- 25992918
TI  - Effect of Corticosteroid on Renal Water and Sodium Excretion in Symptomatic Heart
      Failure: Prednisone for Renal Function Improvement Evaluation Study.
AB  - BACKGROUND: Recent evidence indicates that prednisone can potentiate renal
      responsiveness to diuretics in heart failure (HF). However, the optimal dose of
      prednisone is not known. METHOD: Thirty-eight patients with symptomatic HF were
      randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/d,
      n = 8), medium-dose (30 mg/d, n = 10), or high-dose prednisone (60 mg/d, n = 10),
      for 10 days. During this time, we recorded the 24-hour urinary output and the 24
      hour urinary sodium excretion, at baseline, on day 5 and day 10. We also
      monitored the change in the concentration of serum creatinine, angiotensin II,
      aldosterone, high-sensitive C-reactive protein, tumor necrosis factor-alpha,
      interleukin 1beta, and interleukin 6. RESULTS: Low-dose prednisone significantly
      enhanced urine output. However, the effects of medium- and high-dose prednisone
      on urine output were less obvious. As for renal sodium excretion, high-dose
      prednisone induced a more potent natriuresis than low-dose prednisone. Despite
      the potent diuresis and natriuresis induced by prednisone, serum creatinine,
      angiotensin II, and aldosterone levels were not elevated. These favorable effects
      were not associated with an inflammatory suppression by glucocorticoids.
      CONCLUSIONS: Only low-dose prednisone significantly enhanced urine output.
      However, high-dose prednisone induced a more potent renal sodium excretion than
      low-dose prednisone.

PMID- 25992920
TI  - Mistletoe infection in an oak forest is influenced by competition and host size.
AB  - Host size and distance from an infected plant have been previously found to
      affect mistletoe occurrence in woody vegetation but the effect of host plant
      competition on mistletoe infection has not been empirically tested. For an
      individual tree, increasing competition from neighbouring trees decreases its
      resource availability, and resource availability is also known to affect the
      establishment of mistletoes on host trees. Therefore, competition is likely to
      affect mistletoe infection but evidence for such a mechanism is lacking. Based on
      this, we hypothesised that the probability of occurrence as well as the abundance
      of mistletoes on a tree would increase not only with increasing host size and
      decreasing distance from an infected tree but also with decreasing competition by
      neighbouring trees. Our hypothesis was tested using generalized linear models
      (GLMs) with data on Loranthus europaeus Jacq., one of the two most common
      mistletoes in Europe, on 1015 potential host stems collected in a large fully
      mapped plot in the Czech Republic. Because many trees were multi-stemmed, we ran
      the analyses for both individual stems and whole trees. We found that the
      probability of mistletoe occurrence on individual stems was affected mostly by
      stem size, whereas competition had the most important effects on the probability
      of mistletoe occurrence on whole trees as well as on mistletoe abundance.
      Therefore, we confirmed our hypothesis that competition among trees has a
      negative effect on mistletoe occurrence. 

PMID- 25992919
TI  - Vascular Effects of Endothelin Receptor Antagonists Depends on Their Selectivity
      for ETA Versus ETB Receptors and on the Functionality of Endothelial ETB
      Receptors.
AB  - INTRODUCTION: The goal of this study was to characterize the role of Endothelin
      (ET) type B receptors (ETB) on vascular function in healthy and diseased
      conditions and demonstrate how it affects the pharmacological activity of ET
      receptor antagonists (ERAs). METHODS: The contribution of the ETB receptor to
      vascular relaxation or constriction was characterized in isolated arteries from
      healthy and diseased rats with systemic (Dahl-S) or pulmonary hypertension
      (monocrotaline). Because the role of ETB receptors is different in pathological
      vis-a-vis normal conditions, we compared the efficacy of ETA-selective and dual
      ETA/ETB ERAs on blood pressure in hypertensive rats equipped with telemetry.
      RESULTS: In healthy vessels, ETB receptors stimulation with sarafotoxin S6c
      induced vasorelaxation and no vasoconstriction. In contrast, in arteries of rats
      with systemic or pulmonary hypertension, endothelial ETB-mediated relaxation was
      lost while vasoconstriction on stimulation by sarafotoxin S6c was observed. In
      hypertensive rats, administration of the dual ETA/ETB ERA macitentan on top of a
      maximal effective dose of the ETA-selective ERA ambrisentan further reduced blood
      pressure, indicating that ETB receptors blockade provides additional benefit.
      CONCLUSIONS: Taken together, these data suggest that in pathology, dual ETA/ETB
      receptor antagonism can provide superior vascular effects compared with ETA
      selective receptor blockade.

PMID- 25992921
TI  - The multi-organ chip--a microfluidic platform for long-term multi-tissue
      coculture.
AB  - The ever growing amount of new substances released onto the market and the
      limited predictability of current in vitro test systems has led to a high need
      for new solutions for substance testing. Many drugs that have been removed from
      the market due to drug-induced liver injury released their toxic potential only
      after several doses of chronic testing in humans. However, a controlled
      microenvironment is pivotal for long-term multiple dosing experiments, as even
      minor alterations in extracellular conditions may greatly influence the cell
      physiology. We focused within our research program on the generation of a
      microengineered bioreactor, which can be dynamically perfused by an on-chip pump
      and combines at least two culture spaces for multi-organ applications. This
      circulatory system mimics the in vivo conditions of primary cell cultures better
      and assures a steadier, more quantifiable extracellular relay of signals to the
      cells. For demonstration purposes, human liver equivalents, generated by
      aggregating differentiated HepaRG cells with human hepatic stellate cells in
      hanging drop plates, were cocultured with human skin punch biopsies for up to 28
      days inside the microbioreactor. The use of cell culture inserts enables the skin
      to be cultured at an air-liquid interface, allowing topical substance exposure.
      The microbioreactor system is capable of supporting these cocultures at near
      physiologic fluid flow and volume-to-liquid ratios, ensuring stable and
      organotypic culture conditions. The possibility of long-term cultures enables the
      repeated exposure to substances. Furthermore, a vascularization of the
      microfluidic channel circuit using human dermal microvascular endothelial cells
      yields a physiologically more relevant vascular model. 

PMID- 25992922
TI  - Correction: Global estimates of prevalent and incident herpes simplex virus type
      2 infections in 2012.

PMID- 25992923
TI  - Challenges for improving quality of life in Chagas disease.

PMID- 25992924
TI  - Health-related quality of life in patients with Chagas disease: a review of the
      evidence.
AB  - Chagas disease (ChD), a neglected tropical disease caused by infection with the
      parasite Trypanosoma cruzi (T. cruzi), remains a serious public health issue in
      Latin America and is an emerging disease in several non-endemic countries, where
      knowledge of the condition and experience with its clinical management are
      limited. Regionally, the disease is the major cause of disability secondary to
      tropical diseases in young adults. Health-related quality of life (HRQoL)
      impairment is common in patients with ChD, especially in those with Chagas
      dilated cardiomyopathy, the most severe manifestation of the disease, which
      frequently leads to heart failure. The aim of this review was to conduct a
      literature search for studies that have evaluated the determining factors of
      HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and
      experimental studies, as well as clinical trials that evaluated the HRQoL in ChD
      patients aged 18 to 60 years and are presenting an explicit description of
      statistical analysis. Using a combination of keywords based on Descriptors in
      Health Sciences (DeCS) and Medical Subject Headings (MeSH) for searches in PubMed
      and the Scientific Electronic Library Online (SciELO), 148 studies were found.
      After exclusions, 12 studies were selected for analysis. Three main findings were
      extracted from these studies: 1) cardiac involvement is associated with a worse
      HRQoL in ChD patients; 2) HRQoL is associated with the patients' functional
      capacity; and 3) simple and inexpensive therapeutic measures are effective for
      improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the
      effectiveness of non-surgical conservative treatment, and cardiac involvement are
      important determining factors for the HRQoL in ChD patients. 

PMID- 25992925
TI  - The effectiveness of a rotavirus vaccine in preventing hospitalizations and
      deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi
      experimental study.
AB  - INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea
      in children worldwide. Considering that a rotavirus vaccine (G1P8, strain
      RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to
      study its effectiveness and safety regarding intestinal intussusception. METHODS:
      A quasi-experimental trial was performed in which the primary outcome was the
      number of hospitalizations that were presumably due to acute infectious diarrhea
      per 100,000 children at risk (0-4 years old). The secondary outcomes included
      mortality due to acute infectious diarrhea and the intestinal intussusception
      rates in children in the same age range. We analyzed three scenarios: Health
      Division XIII of the State of Sao Paulo (DRS XIII) from 2002 to 2008, the State
      of Sao Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the
      hospitalization rates for 100,000 children in the pre- and post-vaccination
      periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249,
      respectively, for the State of Sao Paulo (RR=0.79), and 718 and 576,
      respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the
      pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII
      (RR=0.66), 5.5 and 2.5, respectively, for the State of Sao Paulo (RR=0.47), and
      15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of
      intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in
      the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent
      rotavirus vaccine was demonstrated to be effective in preventing the
      hospitalizations and deaths of children that were presumably due to acute
      infectious diarrhea, without increasing the risk of intestinal intussusception.

PMID- 25992926
TI  - Toll-like receptor 3 gene polymorphisms are not associated with the risk of
      hepatitis B and hepatitis C virus infection.
AB  - INTRODUCTION: The present study investigated the prevalence of two single
      nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in
      patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV).
      METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were
      subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs
      rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl
      transpeptidase (GGT), and prothrombin time (PT). A healthy control group was
      investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS:
      No significant differences in allele, genotype and haplotype frequencies were
      observed between the investigated groups, and no association was observed between
      the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA
      (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT
      (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305;
      p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels.
      CONCLUSIONS: This genetic analysis revealed the absence of an association between
      the polymorphisms investigated and susceptibility to HBV and HCV infection;
      however, these polymorphisms might be associated with a greater degree of biliary
      damage during the course of HCV infection.

PMID- 25992927
TI  - Evaluation of arboviruses of public health interest in free-living non-human
      primates (Alouatta spp., Callithrix spp., Sapajus spp.) in Brazil.
AB  - INTRODUCTION: The aim of the present study was to evaluate the presence of
      arboviruses from the Flavivirus genus in asymptomatic free-living non-human
      primates (NHPs) living in close contact with humans and vectors in the States of
      Parana and Mato Grosso do Sul, Brazil. METHODS: NHP sera samples (total n = 80,
      Alouatta spp. n = 07, Callithrix spp. n = 29 and Sapajus spp. n = 44) were
      screened for the presence of viral genomes using reverse transcription polymerase
      chain reaction and 10% polyacrylamide gel electrophoresis techniques. RESULTS:
      All of the samples were negative for the Flavivirus genome following the 10%
      polyacrylamide gel electrophoresis analysis. CONCLUSIONS: These negative results
      indicate that the analyzed animals were not infected with arboviruses from the
      Flavivirus genus and did not represent a risk for viral transmission through
      vectors during the period in which the samples were collected.

PMID- 25992928
TI  - Opportunistic infections among individuals with HIV-1/AIDS in the highly active
      antiretroviral therapy era at a Quaternary Level Care Teaching Hospital.
AB  - INTRODUCTION: In this study, clinical-laboratory and epidemiological
      characteristics are described for a group of 700 individuals with HIV (human
      immunodeficiency virus)/AIDS (acquired immunodeficiency syndrome) in the ART
      (antiretroviral therapy) era at a teaching hospital that provides a quaternary
      level of care, with an emphasis on opportunistic infections (OIs), co-infections
      and immune profile. METHODS: A retrospective cross-sectional study of AIDS cases
      was conducted from 1998 to 2008 by reviewing medical records from the Base
      Hospital/FUNFARME (Fundacao Faculdade Regional de Medicina), Sao Jose do Rio
      Preto, Sao Paulo, Brazil. RESULTS: The individuals were 14 to 75 years of age,
      and 458 were males. Heterosexuals accounted for 31.1% of all patients. Eighty
      three percent were on ART, and 33.8% of those presented difficulties with
      treatment adherence. OIs were analyzed from medical records, and Pneumocystis
      jiroveci pneumonia was the most prevalent, regardless of the LTCD4+ (TCD4+
      Lymphocytes) levels. Individuals whose viral loads were >=10,000 showed a 90%
      greater chance of neurotoxoplasmosis. For P. jiroveci pneumonia,
      neurotoxoplasmosis, esophageal candidiasis, pulmonary tuberculosis and
      neurocryptococcosis, the chances of infection were higher among patients with
      LTCD4+ levels below 200 cells/mm3. HIV/hepatitis C virus (HCV) and HIV/hepatitis
      B virus (HBV) co-infections were significantly associated with death.
      CONCLUSIONS: OIs remain frequent in the ART era even in populations where the
      access to medical care is considered satisfactory.

PMID- 25992929
TI  - Susceptibility characterization of residual Brazilian populations of Triatoma
      infestans Klug, 1834 (Hemiptera: Reduviidae) to deltamethrin pyrethroid.
AB  - INTRODUCTION: Despite years of efforts towards the elimination of Triatoma
      infestans in Brazil, residual foci still persist in some areas of the States of
      Bahia and Rio Grande do Sul. The persistence of these T. infestans populations in
      the country has two different origins of equal concern: operational failures or
      insecticide resistance. Thus, the objective of this study was to characterize the
      susceptibility profile of the residual Brazilian populations of T. infestans to
      deltamethrin. METHODS: The susceptibility reference lineage was derived from
      Cipein/Argentina. The populations studied were manually collected using a
      dislodging agent in peridomiciles in the States of Bahia (Novo Horizonte) and of
      Rio Grande do Sul (Santa Rosa and Doutor Mauricio Cardoso). Serial dilutions of
      deltamethrin were prepared and applied at the dorsal abdomen of first instar
      nymphs. The control group received only pure acetone. Mortality was evaluated
      after 72h. Qualitative tests assessed the mortality of a diagnostic dose of
      1xLD99 (2.76ng a.i./nymph) determined for the susceptibility reference lineage.
      RESULTS: The susceptibility profile characterization of the T. infestans
      populations revealed an RR50 ranging from 1.73 to 3.26. The mortality percentage
      in response to a diagnostic dose was 100%. The results obtained in the
      quantitative and qualitative assays corresponded for all populations.
      CONCLUSIONS: The results of this study indicate that the persistence of residual
      foci of T. infestans in Bahia and Rio Grande do Sul is not related to insecticide
      resistance but may be associated with operational failures. In Rio Grande do Sul,
      we must consider the possibility of continuous reinfestation by Argentinian
      individuals, which justifies active and efficient epidemiological surveillance.

PMID- 25992930
TI  - Distribution of extended-spectrum beta-lactamase types in a Brazilian tertiary
      hospital.
AB  - INTRODUCTION: Epidemiological data on the prevalence of extended-spectrum beta
      lactamases (ESBLs) are scarce in Brazil despite the fact that these data are
      essential for empirical treatment and control measures. The objective of this
      study was to evaluate the prevalence of different ESBLs by type and distribution
      in a tertiary hospital in southern Brazil. METHODS: We evaluated 1,827
      enterobacterial isolates between August 2003 and March 2008 isolated from
      patients at a tertiary hospital. Samples were identified using a Vitek automated
      system and were confirmed by biochemical testing. The identified ESBL strains
      were characterized by phenotypic methods, polymerase chain reaction (PCR), and
      sequencing. Genetic similarities were evaluated by pulsed-field gel
      electrophoresis. RESULTS: It was 390 (21.3%) ESBL-producing strains, which
      expressed the ESBLs CTX-M (292), SHV (84), CTX and SHV (10), TEM (2), and PER
      (2). CONCLUSIONS: The prevalence of ESBL-expressing strains was high, especially
      in Klebsiella pneumoniae and Enterobacter spp. CTX-M was the predominant type of
      ESBL observed, and its genetic variability indicates a polyclonal distribution.

PMID- 25992931
TI  - Chlamydia trachomatis serotype A infections in the Amazon region of Brazil:
      prevalence, entry and dissemination.
AB  - INTRODUCTION: Chlamydia infection is associated with debilitating human diseases
      including trachoma, pneumonia, coronary heart disease and urogenital diseases.
      Serotypes of C. trachomatis show a fair correlation with the group of diseases
      they cause, and their distribution follows a well-described geographic pattern.
      Serotype A, a trachoma-associated strain, is known for its limited dissemination
      in the Middle East and Northern Africa. However, knowledge on the spread of
      bacteria from the genus Chlamydia as well as the distribution of serotypes in
      Brazil is quite limited. METHODS: Blood samples of 1,710 individuals from ten
      human population groups in the Amazon region of Brazil were examined for
      antibodies to Chlamydia using indirect immunofluorescence and
      microimmunofluorescence assays. RESULTS: The prevalence of antibodies to
      Chlamydia ranged from 23.9% (Wayana-Apalai) to 90.7% (Awa-Guaja) with a mean
      prevalence of 50.2%. Seroreactivity was detected to C. pneumoniae and to all
      serotypes of C. trachomatis tested; furthermore, we report clear evidence of the
      as-yet-undescribed occurrence of serotype A of C. trachomatis. CONCLUSIONS:
      Specific seroreactivity not only accounts for the large extent of dissemination
      of C. trachomatis in the Amazon region of Brazil but also shows an expanded area
      of occurrence of serotype A outside the epidemiological settings previously
      described. Furthermore, these data suggest possible routes of Chlamydia
      introduction into the Amazon region from the massive human migration that
      occurred during the 1,700s.

PMID- 25992932
TI  - Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease
      patients with no apparent cardiac involvement.
AB  - INTRODUCTION: Exercise-induced ventricular arrhythmia (EIVA) and autonomic
      imbalance are considered as early markers of heart disease in Chagas disease
      (ChD) patients. The objective of the present study was to verify the differences
      in the occurrence of EIVA and autonomic maneuver indexes between healthy
      individuals and ChD patients with no apparent cardiac involvement. METHODS: A
      total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5)
      years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using
      echocardiography, symptom-limited treadmill exercise testing and autonomic
      function tests. RESULTS: The occurrence of EIVA was higher in the chagasic group
      (48%) than in the control group (23.7%) during both the effort and the recovery
      phases. Frequent ventricular contractions occurred only in the patient group.
      Additionally, the respiratory sinus arrhythmia index was significantly lower in
      the chagasic individuals compared with the control group. CONCLUSIONS: ChD
      patients with no apparent cardiac involvement had a higher frequency of EIVA as
      well as more vagal dysfunction by respiratory sinus arrhythmia. These results
      suggest that even when asymptomatic, ChD patients possess important
      arrhythmogenic substrates and subclinical disease.

PMID- 25992933
TI  - Spatiotemporal analysis of reported cases of acute Chagas disease in the State of
      Pernambuco, Brazil, from 2002 to 2013.
AB  - INTRODUCTION: Control strategies to eliminate the transmission of Chagas disease
      by insect vectors have significantly decreased the number of reported acute cases
      in Brazil. However, data regarding the incidence and distribution of acute Chagas
      disease cases in the State of Pernambuco are unavailable in the literature.
      METHODS: A geographical information system was used to delineate the
      spatiotemporal distribution profile of the cases from 2002 to 2013 in 185
      municipalities of Pernambuco based on the municipality where notification
      occurred. The results were presented in digital maps generated by the TerraView
      software (INPE). RESULTS: A total of 302 cases of acute disease were recorded in
      37.8% of the municipalities, for a total of 0.13 cases per 1,000,000 inhabitants
      per year. Out of the 302 cases, 99.3% were reported between 2002 and 2006. The
      most affected municipalities were Carnaubeira da Penha, Mirandiba and Terra Nova.
      The risk maps showed a significant decrease in the number of notifications and a
      concentration of cases in the Midwest region. CONCLUSIONS: This study highlights
      a significant decrease in new cases of acute Chagas disease in Pernambuco
      starting in 2006 when Brazil received an international certification for the
      interruption of vectorial transmission by Triatoma infestans. However, control
      strategies should still be encouraged because other triatomine species can also
      transmit the parasite; moreover, other transmission modes must not be neglected.

PMID- 25992934
TI  - Comparison of recombinant A2-ELISA with rKE16 dipstick and direct agglutination
      tests for diagnosis of visceral leishmaniasis in dogs in Northwestern Iran.
AB  - INTRODUCTION: Various methods are used for the diagnosis of visceral
      leishmaniasis (VL), such as microscopic examination, culture and inoculation of
      laboratory animals; however, serological assays are commonly used for the
      detection of antibodies in serum samples with a wide range of specificity and
      sensitivity. METHODS: The purpose of this study was to compare three serological
      methods, including rA2-ELISA, the recombinant KE16 (rKE16) dipstick test and the
      direct agglutination test (DAT), for the detection of antibodies against VL
      antigens. The assays utilized 350 statistically based random serum samples from
      domestic dogs with clinical symptoms as well as samples from asymptomatic and
      healthy dogs from rural and urban areas of the Meshkinshahr district,
      northwestern Iran. RESULTS: Samples were assessed, and the following positive
      rates were obtained: 11.5% by rKE16, 26.9% by DAT and 49.8% by ELISA. The
      sensitivity among symptomatic dogs was 32.4% with rKE16, 100% with DAT and 52.9%
      with ELISA. Conversely, rA2-ELISA was less specific for asymptomatic dogs, at
      46.5%, compared with DAT, at 88.9%. CONCLUSIONS: This study recommends rA2-ELISA
      as a parallel assay combined with DAT to detect VL infection among dogs. Further
      evaluations should be performed to develop an inexpensive and reliable serologic
      test for the detection of Leishmania infantum among infected dogs.

PMID- 25992935
TI  - The stigma and prejudice of leprosy: influence on the human condition.
AB  - INTRODUCTION: To analyze the knowledge, feelings and perceptions involving
      patients affected by leprosy, as a better understanding of these factors may be
      useful to decrease the stigma and prejudice associated with the condition.
      METHODS: The study cohort consisted of 94 patients who underwent treatment for
      leprosy at the Health Units in the City of Cuiaba, Mato Grosso (MT), Brazil. The
      study questionnaire included items to collect information on socio-demographic
      data, knowledge about the disease, stigma, prejudice, self-esteem and quality of
      life of leprosy patients. Bivariate analyses were used to assess the data based
      on the chi-square test with a 5% significance threshold. RESULTS: The results
      revealed that the study population consisted predominantly of males (55.3%) with
      an income between 1 and 3 times the minimum wage (67%). The survey respondents
      reported that the most significant difficulties related to the treatment were the
      side effects (44.7%) and the duration of the treatment (28.7%). A total of 72.3%
      of the subjects were knowledgeable about the disease, of whom 26.6% had the
      leprosy reaction. Stigma and prejudice were cited by 93.6% of the participants.
      Based on the responses, 40.4% of patients reported being depressed and sad, and
      69.1% of the subjects encountered problems at work after being diagnosed. A total
      of 45.7% of the patients rated their quality of life between bad and very bad.
      CONCLUSIONS: Our results suggest that leprosy causes suffering in patients beyond
      pain and discomfort and greatly influences social participation.

PMID- 25992936
TI  - Using the International Classification of Functioning, Disability and Health as a
      tool for analysis of the effect of physical therapy on spasticity in HAM/TSP
      patients.
AB  - INTRODUCTION: This study aimed to evaluate spasticity in human T-lymphotropic
      virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
      patients before and after physical therapy using the International Classification
      of Functioning, Disability and Health (ICF). METHODS: Nine subjects underwent
      physical therapy. Spasticity was evaluated using the Modified Ashworth Scale. The
      obtained scores were converted into ICF body functions scores. RESULTS: The
      majority of subjects had a high degree of spasticity in the quadriceps muscles.
      According to the ICF codes, the spasticity decreased after 20 sessions of
      physical therapy. CONCLUSIONS: The ICF was effective in evaluating spasticity in
      HAM/TSP patients.

PMID- 25992937
TI  - The use of saliva as a practical and feasible alternative to urine in large-scale
      screening for congenital cytomegalovirus infection increases inclusion and
      detection rates.
AB  - INTRODUCTION: Although urine is considered the gold-standard material for the
      detection of congenital cytomegalovirus (CMV) infection, it can be difficult to
      obtain in newborns. The aim of this study was to compare the efficiency of
      detection of congenital CMV infection in saliva and urine samples. METHODS: One
      thousand newborns were included in the study. Congenital cytomegalovirus
      deoxyribonucleic acid (DNA) was detected by polymerase chain reaction (PCR).
      RESULTS: Saliva samples were obtained from all the newborns, whereas urine
      collection was successful in only 333 cases. There was no statistically
      significant difference between the use of saliva alone or saliva and urine
      collected simultaneously for the detection of CMV infection. CONCLUSIONS: Saliva
      samples can be used in large-scale neonatal screening for CMV infection.

PMID- 25992938
TI  - A rapid and simple method to detect ESBL in Enterobacter cloacae based on MIC of
      cefepime.
AB  - INTRODUCTION: The aim of this study was to identify a rapid and simple phenotypic
      method for extended-spectrum beta-lactamase (ESBL) detection in Enterobacter
      cloacae. METHODS: A total of 79 consecutive, non-repeated samples of E. cloacae
      were evaluated. Four phenotypic methods were applied for ESBL detection, results
      were compared to multiplex polymerase chain reaction (PCR) as the gold standard
      reference method: 1) ceftazidime and cefotaxime disks with and without
      clavulanate, both with boronic acid added; 2) disk approximation using cefepime
      and amoxicillin/clavulanate; 3) ESBL screening by minimum inhibitory
      concentration (MIC) >= 16ug/mL and 4) by MIC >= 2ug/mL for cefepime. RESULTS:
      Method 4 showed the best combination of sensitivity (100%) and specificity (94%).
      CONCLUSIONS: MIC >= 2ug/mL for cefepime would be very useful for the phenotypic
      detection of ESBL in samples of E. cloacae.

PMID- 25992939
TI  - Production of metallo-beta-lactamase among Pseudomonas aeruginosa strains
      isolated in the State of Sergipe, Brazil.
AB  - INTRODUCTION: Acquired production of metallo-beta-lactamases is an important
      mechanism of resistance in Pseudomonas aeruginosa. The objective of this study
      was to investigate the production of metallo-beta-lactamase and the genetic
      diversity among ceftazidime-resistant P. aeruginosa isolates from State of
      Sergipe, Brazil. METHODS: Metallo-beta-lactamase was investigated using the disk
      approximation test and polymerase chain reaction (PCR). Genetic diversity was
      evaluated by pulsed-field gel electrophoresis (PFGE). RESULTS: A total of 48
      (51.6%) isolates were resistant to ceftazidime. Six (12.2%) of these were
      positive for metallo-beta-lactamase production. Only two (4.1%) of the
      ceftazidime-resistant isolates carried the bla SPM-1 gene. CONCLUSIONS:
      Production of metallo-beta-lactamases was not the main mechanism of resistance to
      ceftazidime and carbapenems among P. aeruginosa strains in Sergipe, Brazil.

PMID- 25992940
TI  - Congenital and maternal syphilis in the capital of Brazil.
AB  - INTRODUCTION: This study aimed to describe the epidemiology of congenital and
      maternal syphilis in the Brazilian Federal District in 2010.  METHODS: A
      retrospective descriptive study was conducted on the basis of the cases recorded
      in the System of Notifiable Disease Information. RESULTS: The study population
      comprised 133 cases of congenital syphilis; of these, 116 (52.6%) mothers
      received prenatal care, and 70 (60.4%) were diagnosed with syphilis during
      pregnancy. Only 1 mother was adequately treated, and 100 (75.2%) of the pregnant
      women's partners did not undergo treatment for syphilis.  CONCLUSIONS: Although
      mothers attended prenatal care, not all were diagnosed during pregnancy or
      received adequate treatment for syphilis, as their partners did not undergo
      treatment for syphilis.

PMID- 25992941
TI  - Occurrence of Cryptosporidium spp., Giardia spp. and other pathogenic intestinal
      parasites in the Beberibe River in the State of Pernambuco, Brazil.
AB  - INTRODUCTION: Transmission of pathogenic protozoa and helminths by water is a
      serious public health problem. In this study, we analyzed the presence of these
      organisms in the Beberibe River in Pernambuco, Brazil. METHODS: Parasite analysis
      was performed using the Hoffman, Pons, & Janer method followed by centrifugation
      and preparation of slides by staining with acetic acid and Lugol's solution.
      Protozoan oocysts were isolated by the modified Ziehl Neelsen method. RESULTS:
      Cryptosporidium spp., Giardia spp. and other parasites were found in the Beberibe
      River. CONCLUSIONS: Sanitation companies must assess pathogenic intestinal
      parasites in water basins providing public water and subsequently develop
      improved treatment systems for removal of such parasites.

PMID- 25992942
TI  - An atypical Toxoplasma gondii genotype in a rural Brazilian dog co-infected with
      Leishmania (Viannia) braziliensis.
AB  - Toxoplasmosis and leishmaniasis are two worldwide zoonoses caused by the
      protozoan parasites Toxoplasma gondii and Leishmania spp., respectively. This
      report describes the clinical and laboratorial findings of a co-infection with
      both parasites in a 4-year-old female dog suspected of ehrlichiosis that
      presented anemia, thrombocytopenia, hypoalbuminemia, hyperglobulinemia,
      tachyzoite-like structures to the lung imprints, and polymerase chain reaction
      (PCR) results positive for T. gondii (kidney, lung, and liver) and Leishmania
      spp. Co-infection with Toxoplasma gondii and Leishmania braziliensis was
      confirmed by sequencing; restriction fragment length polymorphism-polymerase
      chain reaction (RFLP-PCR) confirmed an atypical T. gondii genotype circulating in
      dogs that has been reported to cause human congenital toxoplasmosis. 

PMID- 25992943
TI  - Surgical treatment of type I neuritis in a teenage boy with borderline
      tuberculoid leprosy.
AB  - Exacerbation of the immune response against Mycobacterium leprae can lead to
      neuritis, which is commonly treated via immunosuppression with corticosteroids.
      Early neurolysis may be performed concurrently, especially in young patients with
      a risk of functional sequelae. We report the case of a young patient experienced
      intense pain in the left elbow one year after the treatment of tuberculoid
      tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge
      and left ulnar claw. After evaluation, the diagnosis was changed to borderline
      tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early
      neurolysis resulted in rapid reduction of the pain and recovery of motor
      function. 

PMID- 25992944
TI  - Maculopapular rash and Koplik's spots in adult measles.

PMID- 25992945
TI  - Oligoarthritis caused by Borrelia bavariensis, Austria, 2014.
AB  - A case of Lyme oligoarthritis occurred in an 11-year-old boy in Vienna, Austria.
      DNA of Borrelia bavariensis was detected by PCR in 2 aspirates obtained from
      different joints. Complete recovery was achieved after a 4-week course with
      amoxicillin. Lyme arthritis must be considered in patients from Europe who have
      persisting joint effusions. 

PMID- 25992946
TI  - Compressive optical image encryption.
AB  - An optical image encryption technique based on compressive sensing using fully
      optical means has been proposed. An object image is first encrypted to a white
      sense stationary noise pattern using a double random phase encoding (DRPE) method
      in a Mach-Zehnder interferometer. Then, the encrypted image is highly compressed
      to a signal using single-pixel compressive holographic imaging in the optical
      domain. At the receiving terminal, the encrypted image is reconstructed well via
      compressive sensing theory, and the original image can be decrypted with three
      reconstructed holograms and the correct keys. The numerical simulations show that
      the method is effective and suitable for optical image security transmission in
      future all-optical networks because of the ability of completely optical
      implementation and substantially smaller hologram data volume. 

PMID- 25992948
TI  - Hybrid QTAIM and electrostatic potential-based quantum topology phase diagrams
      for water clusters.
AB  - The topological diversity of sets of isomers of water clusters (W = H2O)n, 7 <= n
      <= 10, is analyzed employing the scalar fields of total electronic charge density
      rho(r) and the molecular electrostatic potential (MESP). The features uncovered
      by the MESP are shown to be complementary to those revealed by the theory of
      atoms in molecules (QTAIM) analysis. The MESP is known to exhibit the electron
      localizations such as lone pairs that are central to water cluster behavior.
      Therefore, a 'hybrid' QTAIM and MESP quantum topology phase diagram (QTPD) for
      Wn, 7 <= n <= 10, is introduced in addition to the QTPD. The 'spanning' QTPD with
      upper and lower bounds is constructed from the solutions of the Poincare-Hopf
      relation involving the non-degenerate critical points. The changing subtle
      balance between the planar and three dimensional character of the growing water
      clusters Wn, 4 <= n <= 10, is revealed. Characterization of the structure of the
      QTPDs, possible with new tools, demonstrated the migration of the position of the
      global minimum on the spanning QTPD from the lower bound to upper bound as the
      Wn, 4 <= n <= 10, cluster grows in size. Differences in the structure of the QTPD
      are found between the clusters containing even versus odd monomers for Wn, n = 7
      10. The energetic stability of the clusters which possess even number of monomers
      viz. n = 8, 10 is higher than that of the n = 7, 9 clusters due to relatively
      higher numbers of hydrogen-bond BCPs in the n = 8, 10 clusters, in agreement with
      energetic results reported in the literature. A 'hybrid' QTPD is created from a
      new chemical relation bHB + l >= 2n for Wn that relates the number of hydrogen
      bond bond critical points (bHB) with the number of oxygen lone pairs exclusively
      specified by the negative valued MESP (3,+3) critical points (l). The topologies
      of the subset bHB + l = 2n for Wn, point the way to the discovery of unknown
      'missing' lower energy isomers. A discussion of the relative merits and range of
      applicability of the QTAIM and hybrid-QTPD analyses is included and concludes
      that the hybrid-QTPD analysis for Wn, is more useful for the association with the
      energy minima on the potential energy surface. 

PMID- 25992947
TI  - The Basic/Helix-Loop-Helix Protein Family in Gossypium: Reference Genes and Their
      Evolution during Tetraploidization.
AB  - Basic/helix-loop-helix (bHLH) proteins comprise one of the largest transcription
      factor families and play important roles in diverse cellular and molecular
      processes. Comprehensive analyses of the composition and evolution of the bHLH
      family in cotton are essential to elucidate their functions and the molecular
      basis of cotton development. By searching bHLH homologous genes in sequenced
      diploid cotton genomes (Gossypium raimondii and G. arboreum), a set of cotton
      bHLH reference genes containing 289 paralogs were identified and named as
      GobHLH001-289. Based on their phylogenetic relationships, these cotton bHLH
      proteins were clustered into 27 subfamilies. Compared to those in Arabidopsis and
      cacao, cotton bHLH proteins generally increased in number, but unevenly in
      different subfamilies. To further uncover evolutionary changes of bHLH genes
      during tetraploidization of cotton, all genes of S5a and S5b subfamilies in
      upland cotton and its diploid progenitors were cloned and compared, and their
      transcript profiles were determined in upland cotton. A total of 10 genes of S5a
      and S5b subfamilies (doubled from A- and D-genome progenitors) maintained in
      tetraploid cottons. The major sequence changes in upland cotton included a 15-bp
      in-frame deletion in GhbHLH130D and a long terminal repeat retrotransposon
      inserted in GhbHLH062A, which eliminated GhbHLH062A expression in various
      tissues. The S5a and S5b bHLH genes of A and D genomes (except GobHLH062) showed
      similar transcription patterns in various tissues including roots, stems, leaves,
      petals, ovules, and fibers, while the A- and D-genome genes of GobHLH110 and
      GobHLH130 displayed clearly different transcript profiles during fiber
      development. In total, this study represented a genome-wide analysis of cotton
      bHLH family, and revealed significant changes in sequence and expression of these
      genes in tetraploid cottons, which paved the way for further functional analyses
      of bHLH genes in the cotton genus. 

PMID- 25992950
TI  - Copper-Mediated Aryloxylation and Vinyloxylation of beta-C(sp(3))-H Bond of
      Propionamides with Organosilanes.
AB  - A novel copper-mediated method for the aryloxylation and vinyloxylation of beta
      C(sp(3))-H bonds of propioamides with organosilanes is described. The reaction
      proceeds with the assistance of an 8-aminoquinolyl auxiliary in a tandem way by
      the first oxidation of beta-C(sp(3))-H bonds and subsequent arylation/vinylation
      to give the aryloxylation/vinyloxylation products. This unusual aryloxy/vinyloxy
      forming reaction offers a new avenue for the functionalization of unactivated
      sp(3) C-H bonds in organic synthesis. 

PMID- 25992949
TI  - Are global and regional improvements in life expectancy and in child, adult and
      senior survival slowing?
AB  - Improvements in life expectancy have been considerable over the past hundred
      years. Forecasters have taken to applying historical trends under an assumption
      of continuing improvements in life expectancy in the future. A linear mixed
      effects model was used to estimate the trends in global and regional rates of
      improvements in life expectancy, child, adult, and senior survival, in 166
      countries between 1950 and 2010. Global improvements in life expectancy,
      including both child and adult survival rates, decelerated significantly over the
      study period. Overall life expectancy gains were estimated to have declined from
      5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual
      child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean
      deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to
      decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration
      of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to
      4.2 deaths averted per 1000 per year for an acceleration of 0.03
      deaths/1000/year2. Regional variation in the four measures was substantial. The
      rates of global improvements in life expectancy, child survival, and adult
      survival have declined since 1950 despite an increase in the rate of improvements
      among seniors. We postulate that low-cost innovation, related to the last half
      century progress in health-primarily devoted to children and middle age, is
      reaping diminishing returns on its investments. Trends are uneven across regions
      and measures, which may be due in part to the state of epidemiological transition
      between countries and regions and disparities in the diffusion of innovation,
      accessible only in high-income countries where life expectancy is already
      highest. 

PMID- 25992951
TI  - Rational Design and Facial Synthesis of Li3V2(PO4)3@C Nanocomposites Using Carbon
      with Different Dimensions for Ultrahigh-Rate Lithium-Ion Batteries.
AB  - Li3V2(PO4)3 (LVP) particles dispersed in different inorganic carbons (LVP@C) have
      been successfully synthesized via an in situ synthesis method. The inorganic
      carbon materials with different dimensions including zero-dimensional Super P
      (SP) nanospheres, one-dimensional carbon nanotubes (CNTs), two-dimensional
      graphene nanosheets, and three-dimensional graphite particles. The effects of
      carbon dimensions on the structure, morphology, and electrochemical performance
      of LVP@C composites have been systematically investigated. The carbon materials
      can maintain their original morphology even after oxidation (by NH4VO3) and high
      temperature sintering (850  degrees C). LVP@CNT exhibits the best electrochemical
      performances among all of the samples. At an ultrahigh discharge rate of 100C, it
      presents a discharge capacity of 91.94 mAh g(-1) (69.13% of its theoretical
      capacity) and maintains 79.82% of its original capacity even after 382 cycles.
      Its excellent electrochemical performance makes LVP@CNT a promising cathode
      candidate for lithium-ion batteries. 

PMID- 25992954
TI  - Incorrect table title.

PMID- 25992955
TI  - Indian Hedgehog signaling pathway members are associated with magnetic resonance
      imaging manifestations and pathological scores in lumbar facet joint
      osteoarthritis.
AB  - Indian Hedgehog (HH) has been shown to be involved in osteoarthritis (OA) in
      articular joints, where there is evidence that Indian HH blockade could
      ameliorate OA. It seems to play a prominent role in development of the
      intervertebral disc (IVD) and in postnatal maintenance. There is little work on
      IHH in the IVD. Hence the aim of the current study was to investigate the role of
      Indian Hedgehog in the pathology of facet joint (FJ) OA. 24 patients diagnosed
      with lumbar intervertebral disk herniation or degenerative spinal stenosis were
      included. Preoperative magnetic resonance imaging (MRI) and Osteoarthritis
      Research Society International (OARSI) histopathology grading system was
      correlated to the mRNA levels of GLI1, PTCH1, and HHIP in the FJs. The Weishaupt
      grading and OARSI scores showed high positive correlation (r = 0.894) (P < 0.01).
      MRI Weishaupt grades showed positive correlation with GLI1 (r = 0.491), PTCH1 (r
      = 0.444), and HHIP (r = 0.654) mRNA levels (P < 0.05 in each case). OARSI scores
      were also positively correlated with GLI1 (r = 0. 646), PTCH1 (r = 0. 518), and
      HHIP (r = 0.762) mRNA levels (P < 0.01 in each case). Cumulatively our findings
      indicate that Indian HH signaling is increased in OA and is perhaps a key
      component in OA pathogenesis and progression.

PMID- 25992956
TI  - Evaluation of trail-cameras for analyzing the diet of nesting raptors using the
      Northern Goshawk as a model.
AB  - Diet studies present numerous methodological challenges. We evaluated the
      usefulness of commercially available trail-cameras for analyzing the diet of
      Northern Goshawks (Accipiter gentilis) as a model for nesting raptors during the
      period 2007-2011. We compared diet estimates obtained by direct camera monitoring
      of 80 nests with four indirect analyses of prey remains collected from the nests
      and surroundings (pellets, bones, feather-and-hair remains, and feather-hair-and
      bone remains combined). In addition, we evaluated the performance of the trail
      cameras and whether camera monitoring affected Goshawk behavior. The sensitivity
      of each diet-analysis method depended on prey size and taxonomic group, with no
      method providing unbiased estimates for all prey sizes and types. The cameras
      registered the greatest number of prey items and were probably the least biased
      method for estimating diet composition. Nevertheless this direct method yielded
      the largest proportion of prey unidentified to species level, and it
      underestimated small prey. Our trail-camera system was able to operate without
      maintenance for longer periods than what has been reported in previous studies
      with other types of cameras. Initially Goshawks showed distrust toward the
      cameras but they usually became habituated to its presence within 1-2 days. The
      habituation period was shorter for breeding pairs that had previous experience
      with cameras. Using trail-cameras to monitor prey provisioning to nests is an
      effective tool for studying the diet of nesting raptors. However, the technique
      is limited by technical failures and difficulties in identifying certain prey
      types. Our study also shows that cameras can alter adult Goshawk behavior, an
      aspect that must be controlled to minimize potential negative impacts. 

PMID- 25992957
TI  - QuantiFly: Robust Trainable Software for Automated Drosophila Egg Counting.
AB  - We report the development and testing of software called QuantiFly: an automated
      tool to quantify Drosophila egg laying. Many laboratories count Drosophila eggs
      as a marker of fitness. The existing method requires laboratory researchers to
      count eggs manually while looking down a microscope. This technique is both time
      consuming and tedious, especially when experiments require daily counts of
      hundreds of vials. The basis of the QuantiFly software is an algorithm which
      applies and improves upon an existing advanced pattern recognition and machine
      learning routine. The accuracy of the baseline algorithm is additionally
      increased in this study through correction of bias observed in the algorithm
      output. The QuantiFly software, which includes the refined algorithm, has been
      designed to be immediately accessible to scientists through an intuitive and
      responsive user-friendly graphical interface. The software is also open-source,
      self-contained, has no dependencies and is easily installed
      (https://github.com/dwaithe/quantifly). Compared to manual egg counts made from
      digital images, QuantiFly achieved average accuracies of 94% and 85% for eggs
      laid on transparent (defined) and opaque (yeast-based) fly media. Thus, the
      software is capable of detecting experimental differences in most experimental
      situations. Significantly, the advanced feature recognition capabilities of the
      software proved to be robust to food surface artefacts like bubbles and crevices.
      The user experience involves image acquisition, algorithm training by labelling a
      subset of eggs in images of some of the vials, followed by a batch analysis mode
      in which new images are automatically assessed for egg numbers. Initial training
      typically requires approximately 10 minutes, while subsequent image evaluation by
      the software is performed in just a few seconds. Given the average time per vial
      for manual counting is approximately 40 seconds, our software introduces a
      timesaving advantage for experiments starting with as few as 20 vials. We also
      describe an optional acrylic box to be used as a digital camera mount and to
      provide controlled lighting during image acquisition which will guarantee the
      conditions used in this study. 

PMID- 25992958
TI  - Learning word meanings: overnight integration and study modality effects.
AB  - According to the complementary learning systems (CLS) account of word learning,
      novel words are rapidly acquired (learning system 1), but slowly integrated into
      the mental lexicon (learning system 2). This two-step learning process has been
      shown to apply to novel word forms. In this study, we investigated whether novel
      word meanings are also gradually integrated after acquisition by measuring the
      extent to which newly learned words were able to prime semantically related words
      at two different time points. In addition, we investigated whether modality at
      study modulates this integration process. Sixty-four adult participants studied
      novel words together with written or spoken definitions. These words did not
      prime semantically related words directly following study, but did so after a 24
      hour delay. This significant increase in the magnitude of the priming effect
      suggests that semantic integration occurs over time. Overall, words that were
      studied with a written definition showed larger priming effects, suggesting
      greater integration for the written study modality. Although the process of
      integration, reflected as an increase in the priming effect over time, did not
      significantly differ between study modalities, words studied with a written
      definition showed the most prominent positive effect after a 24-hour delay. Our
      data suggest that semantic integration requires time, and that studying in
      written format benefits semantic integration more than studying in spoken format.
      These findings are discussed in light of the CLS theory of word learning. 

PMID- 25992959
TI  - Metabolic energy-based modelling explains product yielding in anaerobic mixed
      culture fermentations.
AB  - The fermentation of glucose using microbial mixed cultures is of great interest
      given its potential to convert wastes into valuable products at low cost,
      however, the difficulties associated with the control of the process still pose
      important challenges for its industrial implementation. A deeper understanding of
      the fermentation process involving metabolic and biochemical principles is very
      necessary to overcome these difficulties. In this work a novel metabolic energy
      based model is presented that accurately predicts for the first time the
      experimentally observed changes in product spectrum with pH. The model predicts
      the observed shift towards formate production at high pH, accompanied with
      ethanol and acetate production. Acetate (accompanied with a more reduced product)
      and butyrate are predicted main products at low pH. The production of propionate
      between pH 6 and 8 is also predicted. These results are mechanistically explained
      for the first time considering the impact that variable proton motive potential
      and active transport energy costs have in terms of energy harvest over different
      products yielding. The model results, in line with numerous reported experiments,
      validate the mechanistic and bioenergetics hypotheses that fermentative mixed
      cultures products yielding appears to be controlled by the principle of maximum
      energy harvest and the necessity of balancing the redox equivalents in absence of
      external electron acceptors. 

PMID- 25992960
TI  - Reticulocalbin-1 facilitates microglial phagocytosis.
AB  - Phagocytosis is critical to the clearance of apoptotic cells, cellular debris and
      deleterious metabolic products for tissue homeostasis. Phagocytosis ligands
      directly recognizing deleterious cargos are the key to defining the functional
      roles of phagocytes, but are traditionally identified on a case-by-case basis
      with technical challenges. As a result, extrinsic regulation of phagocytosis is
      poorly defined. Here we demonstrate that microglial phagocytosis ligands can be
      systematically identified by a new approach of functional screening. One of the
      identified ligands is reticulocalbin-1 (Rcn1), which was originally reported as a
      Ca2+-binding protein with a strict expression in the endoplasmic reticulum. Our
      results showed that Rcn1 can be secreted from healthy cells and that secreted
      Rcn1 selectively bound to the surface of apoptotic neurons, but not healthy
      neurons. Independent characterization revealed that Rcn1 stimulated microglial
      phagocytosis of apoptotic but not healthy neurons. Ingested apoptotic cells were
      targeted to phagosomes and co-localized with phagosome marker Rab7. These data
      suggest that Rcn1 is a genuine phagocytosis ligand. The new approach described in
      this study will enable systematic identification of microglial phagocytosis
      ligands with broad applicability to many other phagocytes. 

PMID- 25992961
TI  - Protein purification technique that allows detection of sumoylation and
      ubiquitination of budding yeast kinetochore proteins Ndc10 and Ndc80.
AB  - Post-translational Modifications (PTMs), such as phosphorylation, methylation,
      acetylation, ubiquitination, and sumoylation, regulate the cellular function of
      many proteins. PTMs of kinetochore proteins that associate with centromeric DNA
      mediate faithful chromosome segregation to maintain genome stability. Biochemical
      approaches such as mass spectrometry and western blot analysis are most commonly
      used for identification of PTMs. Here, a protein purification method is described
      that allows the detection of both sumoylation and ubiquitination of the
      kinetochore proteins, Ndc10 and Ndc80, in Saccharomyces cerevisiae. A strain that
      expresses polyhistidine-Flag-tagged Smt3 (HF-Smt3) and Myc-tagged Ndc10 or Ndc80
      was constructed and used for our studies. For detection of sumoylation, we
      devised a protocol to affinity purify His-tagged sumoylated proteins by using
      nickel beads and used western blot analysis with anti-Myc antibody to detect
      sumoylated Ndc10 and Ndc80. For detection of ubiquitination, we devised a
      protocol for immunoprecipitation of Myc-tagged proteins and used western blot
      analysis with anti-Ub antibody to show that Ndc10 and Ndc80 are ubiquitinated.
      Our results show that epitope tagged-protein of interest in the His-Flag tagged
      Smt3 strain facilitates the detection of multiple PTMs. Future studies should
      allow exploitation of this technique to identify and characterize protein
      interactions that are dependent on a specific PTM. 

PMID- 25992963
TI  - Binge eating as a meaningful experience in bulimia nervosa and anorexia nervosa:
      a qualitative analysis.
AB  - BACKGROUND: Clinical studies describe binge eating as a reaction to hunger,
      negative affect, or the need to dissociate. However, little is known about the
      meanings that women with bulimia nervosa and anorexia nervosa associate with
      binge eating. AIMS: To examine how women with anorexia nervosa and bulimia
      nervosa interpret their experiences of binge eating. METHODS: Sixteen women who
      engaged in binge eating and had been diagnosed with anorexia nervosa, bulimia
      nervosa, or their subclinical variants were interviewed about their experiences
      of eating disorder. Interview data were analyzed using phenomenologically
      informed thematic analysis. RESULTS: Participants described binge eating as a
      practice through which the self experiences a sense of release, and existential
      emptiness is replaced by overwhelming fullness. CONCLUSION: Meaningful
      experiences of release and fullness are central to binge eating in bulimia
      nervosa and anorexia nervosa, and may contribute to the long-term maintenance of
      this practice.

PMID- 25992964
TI  - Crumpled graphene nanoreactors.
AB  - Nanoreactors are material structures that provide engineered internal cavities
      that create unique confined nanoscale environments for chemical reactions.
      Crumpled graphene nanoparticles or "nanosacks" may serve as nanoreactors when
      filled with reactive or catalytic particles and engineered for a specific
      chemical function. This article explores the behavior of crumpled graphene
      nanoreactors containing nanoscale ZnO, Ag, Ni, Cu, Fe, or TiO2 particles, either
      alone or in combination, in a series of case studies designed to reveal their
      fundamental behaviors. The first case study shows that ZnO nanoparticles undergo
      rapid dissolution inside the nanoreactor cavity accompanied by diffusive release
      of soluble products to surrounding aqueous media through the irregular folded
      shell. This behavior demonstrates the open nature of the sack structure, which
      facilitates rapid small-molecule exchange between inside and outside that is a
      requirement for nanoreactor function. In a case study on copper and silver
      nanoparticles, encapsulation in graphene nanoreactors is shown in some cases to
      enhance their oxidation rate in aqueous media, which is attributed to electron
      transfer from the metal core to graphene that bypasses surface oxides and allows
      reduction of molecular oxygen on the high-area graphene shell. Nanoreactors also
      allow particle-particle electron transfer interactions that are mediated by the
      connecting conductive graphene, which give rise to novel behaviors such as
      galvanic protection of Ag nanoparticles in Ag/Ni-filled nanoreactors, and the
      photochemical control of Ag-ion release in Ag/TiO2-filled nanoreactors. It is
      also shown that internal graphene structures within the sacks provide pockets
      that reduce particle mobility and inhibit particle sintering during thermal
      treatment. Finally, these novel behaviors are used to suggest and demonstrate
      several potential applications for graphene nanoreactors in catalysts, controlled
      release, and environmental remediation. 

PMID- 25992962
TI  - In vivo dynamics of retinal microglial activation during neurodegeneration:
      confocal ophthalmoscopic imaging and cell morphometry in mouse glaucoma.
AB  - Microglia, which are CNS-resident neuroimmune cells, transform their morphology
      and size in response to CNS damage, switching to an activated state with distinct
      functions and gene expression profiles. The roles of microglial activation in
      health, injury and disease remain incompletely understood due to their dynamic
      and complex regulation in response to changes in their microenvironment. Thus, it
      is critical to non-invasively monitor and analyze changes in microglial
      activation over time in the intact organism. In vivo studies of microglial
      activation have been delayed by technical limitations to tracking microglial
      behavior without altering the CNS environment. This has been particularly
      challenging during chronic neurodegeneration, where long-term changes must be
      tracked. The retina, a CNS organ amenable to non-invasive live imaging, offers a
      powerful system to visualize and characterize the dynamics of microglia
      activation during chronic disorders. This protocol outlines methods for long
      term, in vivo imaging of retinal microglia, using confocal ophthalmoscopy (cSLO)
      and CX3CR1(GFP/+) reporter mice, to visualize microglia with cellular resolution.
      Also, we describe methods to quantify monthly changes in cell activation and
      density in large cell subsets (200-300 cells per retina). We confirm the use of
      somal area as a useful metric for live tracking of microglial activation in the
      retina by applying automated threshold-based morphometric analysis of in vivo
      images. We use these live image acquisition and analyses strategies to monitor
      the dynamic changes in microglial activation and microgliosis during early stages
      of retinal neurodegeneration in a mouse model of chronic glaucoma. This approach
      should be useful to investigate the contributions of microglia to neuronal and
      axonal decline in chronic CNS disorders that affect the retina and optic nerve. 

PMID- 25992965
TI  - Severe Acne in Female-to-Male Transgender Patients.

PMID- 25992968
TI  - A Network Flow-based Analysis of Cognitive Reserve in Normal Ageing and
      Alzheimer's Disease.
AB  - Cognitive reserve is the ability to sustain cognitive function even with a
      certain amount of brain damages. Here we investigate the neural compensation
      mechanism of cognitive reserve from the perspective of structural brain
      connectivity. Our goal was to show that normal people with high education levels
      (i.e., cognitive reserve) maintain abundant pathways connecting any two brain
      regions, providing better compensation or resilience after brain damage.
      Accordingly, patients with high education levels show more deterioration in
      structural brain connectivity than those with low education levels before
      symptoms of Alzheimer's disease (AD) become apparent. To test this hypothesis, we
      use network flow measuring the number of alternative paths between two brain
      regions in the brain network. The experimental results show that for normal
      aging, education strengthens network reliability, as measured through flow
      values, in a subnetwork centered at the supramarginal gyrus. For AD, a subnetwork
      centered at the left middle frontal gyrus shows a negative correlation between
      flow and education, which implies more collapse in structural brain connectivity
      for highly educated patients. We conclude that cognitive reserve may come from
      the ability of network reorganization to secure the information flow within the
      brain network, therefore making it more resistant to disease progress. 

PMID- 25992971
TI  - Chest Wall Reconstruction: Evolution Over a Decade and Experience With a Novel
      Technique for Complex Defects.
AB  - BACKGROUND: Chest wall reconstruction (CWR) with biologic matrices has gained
      popularity over the last decade; however, data on this topic remain sparse. The
      aim of this study is to review the different methods and materials used for CWR
      while reviewing and highlighting a novel approach using a biologic inlay and
      synthetic onlay technique for larger, complex high-risk defects. METHODS: A
      retrospective review was performed of all patients who underwent full thickness
      chest wall resection and reconstruction during a 10-year period. Patient
      characteristics, comorbidities, operative data, as well as postoperative wound
      complications and outcomes were reviewed. Different reconstructive methods and
      materials were reviewed and compared. RESULTS: From December 2003 to January
      2014, a total of 81 patients underwent CWR. The indications for
      resection/reconstruction included oncologic in 49 patients (60.5%), desmoids
      tumors in 10 (12.3%), bronchopleural fistula in 3 (3.7%), infection in 7 (8.6%),
      and anatomic deformity in 7 (8.6%) patients. Synthetic and/or acellular dermal
      matrices (ADM) reconstruction was used in 59 patients (10 biologic, 22 synthetic,
      and 27 biologic ADM inlay/synthetic onlay combination). On average, 2.5, 3.5, and
      3.6 ribs were resected in the biologic, synthetic, and combination group,
      respectively (P = 0.1). A greater number of patients in the combination group had
      a history of chemotherapy and/or radiation therapy (P = 0.03) than the synthetic
      or biologic alone groups. Risk analysis demonstrated an association between the
      number of ribs resected and postoperative chest wall complications. The incidence
      of chest wall/wound complications in the synthetic, combination, and biologic
      groups was 31.8%, 22.2%, and 10%, respectively (P = 0.47). CONCLUSIONS: In the
      largest single institution study comparing the use of different reconstructive
      materials, including ADM in CWR, the authors demonstrate that a biologic
      inlay/synthetic onlay may be used effectively for high-risk, large complex
      defects. Early outcomes with this technique are promising. The authors believe
      this combination highlights benefits from both materials because the ADM
      facilitates tissue ingrowth and revascularization, whereas the synthetic
      component provides structural durability. Additional studies with larger sample
      sizes are necessary to further explore the benefits of the combination technique
      to determine if outcomes are better than either material alone when used to
      reconstruct high-risk wounds after larger resections.

PMID- 25992973
TI  - Applying stereotactic injection technique to study genetic effects on animal
      behaviors.
AB  - Stereotactic injection is a useful technique to deliver high titer lentiviruses
      to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown
      gene expression in a relatively focused region without significant damage to the
      brain tissue. After recovery, the injected mouse can be tested on various
      behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test
      (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice
      by measuring the amount of time that a mouse spends in the center of a novel open
      field. A more anxious mouse will spend significantly less time in the center of
      the novel field compared to controls. The FST assesses the anti-depressive
      phenotype by quantifying the amount of time that mice spend immobile when placed
      into a bucket of water. A mouse with an anti-depressive phenotype will spend
      significantly less time immobile compared to control animals. The goal of this
      protocol is to use the stereotactic injection of a lentivirus in conjunction with
      behavioral tests to assess how genetic factors modulate animal behaviors. 

PMID- 25992972
TI  - Differential Nucleosome Occupancies across Oct4-Sox2 Binding Sites in Murine
      Embryonic Stem Cells.
AB  - The binding sequence for any transcription factor can be found millions of times
      within a genome, yet only a small fraction of these sequences encode functional
      transcription factor binding sites. One of the reasons for this dichotomy is that
      many other factors, such as nucleosomes, compete for binding. To study how the
      competition between nucleosomes and transcription factors helps determine a
      functional transcription factor site from a predicted transcription factor site,
      we compared experimentally-generated in vitro nucleosome occupancy with in vivo
      nucleosome occupancy and transcription factor binding in murine embryonic stem
      cells. Using a solution hybridization enrichment technique, we generated a high
      resolution nucleosome map from targeted regions of the genome containing
      predicted sites and functional sites of Oct4/Sox2 regulation. We found that at
      Pax6 and Nes, which are bivalently poised in stem cells, functional Oct4 and Sox2
      sites show high amounts of in vivo nucleosome displacement compared to in vitro.
      Oct4 and Sox2, which are active, show no significant displacement of in vivo
      nucleosomes at functional sites, similar to nonfunctional Oct4/Sox2 binding. This
      study highlights a complex interplay between Oct4 and Sox2 transcription factors
      and nucleosomes among different target genes, which may result in distinct
      patterns of stem cell gene regulation. 

PMID- 25992974
TI  - Synthesis and Biological Evaluation of Novel Olean-28,13beta-lactams as Potential
      Antiprostate Cancer Agents.
AB  - gamma-Lactam is an important structural motif in a large number of biologically
      active natural products and synthetic small pharmaceutical molecules. However,
      there is currently no effective approach to construct gamma-lactam ring directly
      from natural rigid polycyclic amides. Herein, we report a facile methodology for
      synthesis of a new group of olean-28,13beta-lactams (10a-j) from their
      corresponding amides, promoted by an easily available reagent 2,3-dichloro-5,6
      dicyanobenzoquinone (DDQ), through an intramolecular dehydrogenative C-N coupling
      reaction via a radical ion mechanism. Biological evaluation indicated that the
      most active lactam 10h displayed potent antiproliferative activity against human
      cancer cells but 13.84- to 16.92-fold less inhibitory activity on noncancer cells
      in vitro. In addition, 10h significantly inhibited the growth of implanted
      prostate cancer in vivo. Furthermore, 10h induced cell cycle arrest and apoptosis
      and down-regulated the AKT/mTOR signaling in DU-145 cells. Finally, 10h was more
      stable in rat plasma and human liver microsomes than CDDO-Me and had little hERG
      channel inhibitory activity. Collectively, 10h may be a potential antiprostate
      cancer agent for further investigation. 

PMID- 25992975
TI  - Intrathecal delivery of IL-6 reactivates the intrinsic growth capacity of
      pyramidal cells in the sensorimotor cortex after spinal cord injury.
AB  - We have previously demonstrated the growth-promoting effect of intrathecal
      delivery of recombinant rat IL-6 immediately after corticospinal tract (CST)
      injury. Our present study aims to further clarify whether intrathecal delivery of
      IL-6 after CST injury could reactivate the intrinsic growth capacity of pyramidal
      cells in the sensorimotor cortex which project long axons to the spinal cord. We
      examined, by ELISA, levels of cyclic adenosine monophosphate (cAMP), adenylyl
      cyclase (AC, which synthesizes cAMP), phosphodiesterases (PDE, which degrades
      cAMP), and, by RT-PCR, the expression of regeneration-associated genes in the rat
      sensorimotor cortex after intrathecal delivery of IL-6 for 7 days, started
      immediately after CST injury. Furthermore, we injected retrograde neuronal tracer
      Fluorogold (FG) to the spinal cord to label pyramidal cells in the sensorimotor
      cortex, layers V and VI, combined with betaIII-tubulin immunostaining, then we
      analyzed by immunohistochemisty and western blot the expression of the co
      receptor gp-130 of IL-6 family, and pSTAT3 and mTOR, downstream IL-6/JAK/STAT3
      and PI3K/AKT/mTOR signaling pathways respectively. We showed that intrathecal
      delivery of IL-6 elevated cAMP level and upregulated the expression of
      regeneration-associated genes including GAP-43, SPRR1A, CAP-23 and JUN-B, and the
      expression of pSTAT3 and mTOR in pyramidal cells of the sensorimotor cortex. In
      contrast, AG490, an inhibitor of JAK, partially blocked these effects of IL-6.
      All these results indicate that intrathecal delivery of IL-6 immediately after
      spinal cord injury can reactivate the intrinsic growth capacity of pyramidal
      cells in the sensorimotor cortex and these effects of IL-6 were partially
      JAK/STAT3-dependent. 

PMID- 25992977
TI  - Preoperative FeNO as a screening indicator of pulmonary complications after
      abdominal surgery in patients over 60 years old.
AB  - The incidence of pulmonary complications after abdominal surgery is higher than
      that of cardiac complications. The perioperative factors currently used to assess
      the risk of postoperative pulmonary complications (PPCs) are imperfect. FeNO is a
      marker of respiratory system disease related to the airway inflammatory response
      and bronchial hyperresponsiveness; it may be a new indicator to screen PPCs. A
      total of 162 patients over 60 years old scheduled for major abdominal surgery
      under general anesthesia were chosen to measure their preoperative FeNO level.
      Statistical analyses including the receiver operating characteristic (ROC) and
      general linear regression were used to analyze the relationships of FeNO with
      PPCs and other parameters. The medians and quartiles of preoperative FeNO were
      14.33 (9.67-21.10) ppb; the geometric mean was 14.25 ppb. Preoperative FeNO
      correlated to age (P <  0.05), and the coefficient of association was 0.267. ROC
      curve analysis of FeNO and PPCs resulted in a high probability with an area under
      the curve of 0.747 (p = 0.001, 95% confidence interval =0.602-0.893). The cut-off
      level was 30.2 ppb, with 47.06% sensitivity and 93.10% specificity. The positive
      predictive value of the cut-off was 42.11% and negative predictive value was
      93.70%. OR value was 10.83. The magnitude of FeNO in the PPCs group was larger
      than that in the non-PPCs groups 26.20 (11.55 - 39.20) versus 13.50 (9.55-20.00);
      p = 0.008). Preoperative FeNO levels may be used to screen the patients over 60
      years old undergoing abdominal surgery with a lower probability to suffer PPCs
      whoes FeNO values less than 30.2 ppb.

PMID- 25992976
TI  - Temporal fluctuation in North East Baltic Sea region cattle population revealed
      by mitochondrial and Y-chromosomal DNA analyses.
AB  - BACKGROUND: Ancient DNA analysis offers a way to detect changes in populations
      over time. To date, most studies of ancient cattle have focused on their
      domestication in prehistory, while only a limited number of studies have analysed
      later periods. Conversely, the genetic structure of modern cattle populations is
      well known given the undertaking of several molecular and population genetic
      studies. RESULTS: Bones and teeth from ancient cattle populations from the North
      East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5
      samples), Medieval (14), and Post-Medieval (26) periods were investigated by
      sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of
      intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA
      haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle
      populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA
      haplotypes, 24 of which were shared with modern breeds, while 6 were unique to
      the ancient samples. Of seven Y-chromosomal sequences determined from ancient
      samples, six were Y2 and one Y1 haplotype. Combined data including Swedish
      samples from the same periods (64 samples) was compared with the occurrence of Y
      chromosomal haplotypes in modern cattle (1614 samples). CONCLUSIONS: The
      diversity of haplogroups was highest in the Prehistoric samples, where many
      haplotypes were unique. The Medieval and Post-Medieval samples also show a high
      diversity with new haplotypes. Some of these haplotypes have become frequent in
      modern breeds in the Nordic Countries and North-Western Russia while other
      haplotypes have remained in only a few local breeds or seem to have been lost. A
      temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that
      corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post
      Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y
      chromosomal haplotypes by new types of cattle.

PMID- 25992979
TI  - Mn-Mediated Radical-Ionic Annulations of Chiral N-Acylhydrazones.
AB  - Sequencing a free radical addition and nucleophilic substitution enables [3 + 2]
      and [4 + 2] annulations of N-acylhydrazones to afford substituted pyrrolidines
      and piperidines. Photolysis of alkyl iodides in the presence of Mn2(CO)10 leads
      to chemoselective iodine atom abstraction and radical addition to N
      acylhydrazones without affecting alkyl chloride functionality. Using radical
      precursors or acceptors bearing a suitably positioned alkyl chloride, the radical
      addition is followed by further bond construction enabled by radical-polar
      crossover. After the alkyl radical adds to the imine bond, the resulting N
      nucleophile displaces the alkyl chloride leaving group via 5-exo-tet or 6-exo-tet
      cyclizations, furnishing either pyrrolidine or piperidine, respectively. When
      both 5-exo-tet and 6-exo-tet pathways are available, the 5-exo-tet cyclization is
      preferred. Isolation of the intermediate radical adduct, still bearing the alkyl
      chloride functionality, confirms the order of events in this radical-polar
      crossover annulation. A chiral oxazolidinone stereocontrol element in the N
      acylhydrazones provides excellent stereocontrol in these reactions. 

PMID- 25992978
TI  - Direct Interaction of CD40 on Tumor Cells with CD40L on T Cells Increases the
      Proliferation of Tumor Cells by Enhancing TGF-beta Production and Th17
      Differentiation.
AB  - It has recently been reported that the CD40-CD40 ligand (CD40L) interaction is
      important in Th17 development. In addition, transforming growth factor-beta (TGF
      beta) promotes tumorigenesis as an immunosuppressive cytokine and is crucial in
      the development of Th17 cells. This study investigated the role of CD40 in breast
      cancer cells and its role in immunosuppressive function and tumor progression.
      CD40 was highly expressed in the breast cancer cell line MDA-MB231, and its
      stimulation with CD40 antibodies caused the up-regulation of TGF-beta. Direct
      CD40-CD40L interaction between MDA-MB231 cells and activated T cells also
      increased TGF-beta production and induced the production of IL-17, which
      accelerated the proliferation of MDA-MB231 cells through the activation of STAT3.
      Taken together, the direct CD40-CD40L interaction of breast tumor cells and
      activated T cells increases TGF-beta production and the differentiation of Th17
      cells, which promotes the proliferation of breast cancer cells. 

PMID- 25992980
TI  - A man, a gadget, a legacy.

PMID- 25992981
TI  - Practicing evidence-based Orthodontics: How to critically appraise a randomized
      controlled trial.

PMID- 25992982
TI  - Orthodontic movement in deciduous teeth.
AB  - Deciduous teeth exfoliate as a result of apoptosis induced by cementoblasts, a
      process that reveals the mineralized portion of the root while attracting clasts.
      Root resorption in deciduous teeth is slow due to lack of mediators necessary to
      speed it up; however, it accelerates and spreads in one single direction whenever
      a permanent tooth pericoronal follicle, rich in epithelial growth factor (EGF),
      or other bone resorption mediators come near. The latter are responsible for bone
      resorption during eruption, and deciduous teeth root resorption and exfoliation.
      Should deciduous teeth be subjected to orthodontic movement or anchorage,
      mediators local levels will increase. Thus, one should be fully aware that root
      resorption in deciduous teeth will speed up and exfoliation will early occur.
      Treatment planning involving deciduous teeth orthodontic movement and/or
      anchorage should consider: Are clinical benefits relevant enough as to be worth
      the risk of undergoing early inconvenient root resorption? 

PMID- 25992983
TI  - An interview with Sylvia Frazier-Bowers.
AB  - Dr. Frazier-Bowers is an associate professor at the University of North Carolina,
      Chapel Hill (UNC-CH), in the Department of Orthodontics. She received a BA from
      the University of Illinois, Urbana-Champaign, and a DDS from the University of
      Illinois, Chicago. After completing the NIH Dentist-Scientist Program at UNC-CH
      in Orthodontics (Certificate, 97') and Genetics and Molecular Biology (PhD, 99'),
      she completed a post-doctoral fellowship at the University of Texas Health
      Science Center, Houston (UTHSC), in the Department of Orthodontics. Leadership
      positions include president of local NC-AADR (North Carolina (2005-2006);
      director of the AADR Craniofacial Biology group (CBG) 2004-2007; IADR/AADR
      councilor for NC-AADR (2007, 2008, 2012) and for the CBG (2012-2015); member of
      Southern Association of Orthodontists Scientific Affairs Committee (2005-2013)
      and the American Association of Orthodontists Council on Scientific Affairs (2014
      - Present). Dr. Frazier-Bowers also serves various editorial boards including the
      Journal of Dental Research and the Scientific Advisory board for the Consortium
      on Orthodontic Advances in Science and Technology. Her current role as faculty at
      UNC-CH includes conducting human genetic studies to determine the etiology of
      inherited tooth disorders, mentoring students at all levels, teaching graduate
      and pre-doctoral level Growth and Development courses and treating patients in
      the UNC School of Dentistry faculty practice in Orthodontics.

PMID- 25992984
TI  - Influence of magnification and superimposition of structures on cephalometric
      diagnosis.
AB  - OBJECTIVE: The purpose of this study was to assess the influence of magnification
      and superimposition of structures on CBCT-generated lateral cephalometric
      radiographs (LCR) using different segments of the cranium. METHODS: CBCT scans of
      10 patients were selected. Four LCR were generated using Dolphin Imaging(r)
      software: full-face, right side, left side and center of the head. A total of 40
      images were imported into Radiocef Studio 2(r), and the angles of the most common
      cephalometric analyses were traced by the same observer twice and within a 10-day
      interval. Statistical analyses included intraexaminer agreement and comparison
      between methods by means of intraclass correlation coefficient (ICC) and Bland
      Altman agreement tests. RESULTS: Intraexaminer agreement of the angles assessed
      by ICC was excellent (> 0.90) for 83% of measurements, good (between 0.75 and
      0.90) for 15%, and moderate (between 0.50 and 0.75) for 2% of measurements. The
      comparison between methods by ICC was excellent for 68% of measurements, good for
      26%, and moderate for 6%. Variables presenting wider confidence intervals (> 6o)
      in the Bland-Altman tests, in intraexaminer assessment, were: mandibular incisor
      angle, maxillary incisor angle, and occlusal plane angle. And in comparison
      methods the variables with wider confidence interval were: mandibular incisor,
      maxillary incisor, GoGn, occlusal plane angle, Frankfort horizontal plane (FHP),
      and CoA. CONCLUSION: Superimposition of structures seemed to influence the
      results more than magnification, and neither one of them significantly influenced
      the measurements. Considerable individual variability may occur, especially for
      mandibular and maxillary incisors, FHP and occlusal plane.

PMID- 25992985
TI  - Alterations in plaque accumulation and gingival inflammation promoted by
      treatment with self-ligating and conventional orthodontic brackets.
AB  - OBJECTIVE: The aim of the present study was to evaluate, comparatively, the
      periodontal response during orthodontic treatment performed with self-ligating
      and conventional brackets. METHODS: Sixteen Caucasian individuals of both sexes,
      aged between 12 and 16 years old and in permanent dentition were selected. Eight
      individuals were treated with conventional brackets installed on the lower dental
      arch and self-ligating brackets on the upper arch. Another eight individuals
      received self-ligating brackets in the lower arch and conventional brackets in
      the upper arch. The subjects received material and instructions for oral hygiene.
      Visible plaque index (VPI), gingival bleeding index (GBI) and clinical attachment
      level (CAL) were evaluated just after installation of orthodontic appliances, and
      30, 60 and 180 days later. Mann-Whitney test was used to compare differences
      between groups (self-ligating and conventional), two-way ANOVA followed by
      Tukey's test was used to assess CAL at each site of each tooth. Significance
      level was set at 5%. RESULTS: No significant changes were found with regard to
      the assessed parameters (VPI, GBI and CAL) in either one of the systems.
      CONCLUSION: No significant changes were found with regard to the periodontal
      response to orthodontic treatment for the variables assessed and between subjects
      receiving passive self-ligating and conventional brackets. All individuals had
      received oral hygiene instructions and had their periodontal conditions
      monitored.

PMID- 25992986
TI  - Comparison of two scales for evaluation of smile and dental attractiveness.
AB  - OBJECTIVE: To compare the visual analogue scale (VAS) and the simplified Q-sort
      method used to investigate the highest level of agreement among dentists,
      orthodontists and laypeople when assessing smile and dental attractiveness.
      MATERIAL AND METHODS: An album containing 258 photos of 86 individuals with their
      lips at rest, a slight and broad smile, was assessed by 25 dentists (general
      clinicians and various specialties), 23 orthodontists and 27 laypeople with
      regard to smile and dental attractiveness. To this end, both VAS and simplified Q
      sort method were used. Agreements were calculated by intraclass correlation
      coefficient (ICC). RESULTS: For the single measurement between the VAS method and
      the simplified Q-sort method, all simplified Q-sort rates were higher in all
      groups. The simplified Q-sort method results ranged between 0.42 and 0.49 while
      those of the VAS method varied between 0.37 and 0.42. The simplified Q-sort
      method also presented higher mean measurement values (0.95 and 0.96) in
      comparison to VAS (0.94 and 0.95). CONCLUSIONS: Both scales may be considered
      reliable for evaluating smile and dental attractiveness; however, the simplified
      Q-Sort method presented slightly higher values than the VAS method.

PMID- 25992987
TI  - Influence of bleaching and desensitizing gel on bond strength of orthodontic
      brackets.
AB  - OBJECTIVE: The objective of this study was to assess, in vitro, the influence of
      bleaching gel and the use of desensitizing agent over bond strength of ceramic
      brackets bonded to bovine enamel. METHODS: One hundred bovine incisors were
      selected and randomly divided into five groups (n = 20): Group 1, control group
      (without bleaching); Group 2, bleached with 35% hydrogen peroxide; Group 3,
      bleached with 35% hydrogen peroxide (three applications, 15 minutes each) and
      desensitizing agent applied for 10 minutes; Group 4, bleached with 35% hydrogen
      peroxide for 40 minutes; Group 5, bleached with 35% hydrogen peroxide for 40
      minutes with desensitizing agent applied for 10 minutes. Brackets were bonded 7
      days after bleaching and submitted to shear bond strength test after 24 hours at
      a compression rate of 1 mm/minute. After fracture, the adhesive remnant index
      (ARI) was assessed under stereoscopic at 40 x magnification. Shear strength data
      (MPa) were submitted to one-way ANOVA and Tukey's test with significance level
      set at 5%. RESULTS: Group 5 (29.33 MPa) showed significantly higher bond strength
      than Group 1 (19.19 MPa), Group 2 (20.59 MPa) and Group 4 (23.25 MPa), but with
      no difference in comparison to Group 3. There was no significant difference among
      the other groups. The adhesive remnant index showed predominance of score 3, that
      is, all resin remained adhered to enamel for all groups. CONCLUSION: Bleaching
      with 35% hydrogen peroxide with calcium associated with desensitizing agent
      application produced higher bond strength values of brackets bonded to bovine
      enamel.

PMID- 25992988
TI  - A digital volumetric tomography (DVT) study in the mandibular molar region for
      miniscrew placement during mixed dentition.
AB  - OBJECTIVE: To assess bone thickness for miniscrew placement in the mandible
      during mixed dentition by using digital volumetric tomograph (DVT). MATERIAL AND
      METHODS: A total of 15 healthy patients aged 8-10 years old, with early
      exfoliated mandibular second deciduous molar, were included. DVT images of one
      quadrant of the mandible were obtained using Kodak extraoral imaging systems and
      analyzed by Kodak dental imaging software. The error of the method (EM) was
      calculated using Dahlberg's formula. Mean and standard deviation were calculated
      at 6 and 8 mm from the cementoenamel junction (CEJ).Paired t-test was used to
      analyze the measurements. RESULTS: Buccal cortical bone thickness, mesiodistal
      width and buccolingual bone depth at 6 mm were found to be 1.73 + 0.41, 2.15 +
      0.49 and 13.18 + 1.22 mm, respectively; while at 8 mm measurements were 2.42 +
      0.34, 2.48 + 0.33 and 13.65 + 1.25 mm, respectively. EM for buccal cortical bone
      thickness, mesiodistal width and buccolingual bone depth was 0.58, 0.40 and 0.48,
      respectively. The difference in measurement at 6 and 8 mm for buccal cortical
      plate thickness (P < 0.05) and buccolingual bone thickness (P < 0.05) was found
      to be significant, whereas for mesiodistal width it was insignificant (P > 0.05).
      CONCLUSION: Bone thickness measurement has shown promising evidence for safe
      placement of miniscrews in the mandible during mixed dentition. The use of
      miniscrew is the best alternative, even in younger patients.

PMID- 25992989
TI  - Enamel surface evaluation after bracket debonding and different resin removal
      methods.
AB  - OBJECTIVE: To assess enamel surface under scanning electron microscopy (SEM)
      after resin removal and enamel polishing procedures following brackets debonding,
      as well as compare the time required for these procedures. METHODS: A total of
      180 deciduous bovine incisors were used. The enamel surface of each tooth was
      prepared and brackets were bonded with light cured Transbond XT composite resin.
      Brackets were removed in a testing machine. The samples were randomized and
      equally distributed into nine groups according to the resin removal and polishing
      technique: Group 1, 30-blade tungsten carbide bur in high speed; Group 2, 30
      blade tungsten carbide bur in high speed followed by a sequence of 4 Sof-lex
      polishing discs (3M); Group 3, 30-blade tungsten carbide bur in high speed
      followed by Enhance tips (Dentsply). All groups were subdivided into (a)
      unpolished; (b) polished with aluminum oxide paste; and (c) polished with water
      slurry of fine pumice. Subsequently, the enamel surface was assessed and
      statistical analysis was carried out. RESULTS: There were statistically
      significant differences in enamel roughness and removal time among all groups.
      Groups 3a, 3b and 3c appeared to be the most efficient methods of removing resin
      with low damages to enamel. Groups 2a, 2b and 2c were the most time consuming
      procedures, and Group 2a caused more damages to enamel. CONCLUSION: The suggested
      protocol for resin removal is the 30-blade tungsten carbide bur in high speed
      followed by Enhance tips and polishing with aluminum oxide paste. This procedure
      seems to produce less damages and is less time consuming.

PMID- 25992990
TI  - Serum insulin-like growth factor-1 levels in females and males in different
      cervical vertebral maturation stages.
AB  - OBJECTIVE: The aim of this cross sectional study was to assess serum insulin-like
      growth factor-1 (IGF-1) levels in female and male subjects at various cervical
      vertebral maturation (CVM) stages. MATERIAL AND METHODS: The study sample
      consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23
      years. For all subjects, serum IGF-1 level was estimated from blood samples by
      means of chemiluminescence immunoassay (CLIA). CVM was assessed on lateral
      cephalograms using the method described by Baccetti. Serum IGF-1 level and
      cervical staging data of 30 female subjects were included and taken from records
      of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test.
      Bonferroni correction was carried out and alpha value was set at 0.003. RESULTS:
      Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4
      in males. Differences between males and females were observed in mean values of
      IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed
      in CS4 followed by CS5 and third highest in CS3; whereas in females the highest
      mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5.
      Trends of IGF-1 in relation to the cervical stages also differed between males
      and females. The greatest mean serum IGF-1 value for both sexes was comparable,
      for females (397 ng/ml) values were slightly higher than in males (394.8 ng/ml).
      CONCLUSIONS: Males and females showed differences in IGF-1 trends and levels at
      different cervical stages.

PMID- 25992991
TI  - Finite element study on modification of bracket base and its effects on bond
      strength.
AB  - OBJECTIVE: This article aims to analyze the difference in stresses generated in
      the bracket-cement-tooth system by means of a peel load in single and double-mesh
      bracket bases using a three-dimensional finite element computer model. MATERIAL
      AND METHODS: A three-dimensional finite element model of the bracket-cement-tooth
      system was constructed and consisted of 40,536 bonds and 49,201 finite elements
      using a commercial mesh generating programmer (ANSYS 7.0). Both single and double
      mesh bracket bases were modified by varying the diameter from 100-400 um
      progressively, and the spacing between the mesh wires was kept at 300 um for each
      diameter of wire. A peel load was applied on the model to study the stresses
      generated in different layers. RESULTS: In case of double-mesh bracket base,
      there was reduction in stress generation at the enamel in comparison to single
      mesh bracket base. There was no difference in stress generated at the bracket
      layer between single and double-mesh bracket bases. At the impregnated wire mesh
      (IWM), layer stresses increased as the wire diameter of the mesh increased.
      CONCLUSION: Results show that bracket design modification can improve bonding
      abilities and simultaneously reduce enamel damage while debonding. These facts
      may be used in bringing about the new innovative bracket designs for clinical
      use.

PMID- 25992992
TI  - Comparison between full face and hemifacial CBCT cephalograms in clinically
      symmetrical patients: a pilot study.
AB  - INTRODUCTION: One of the advantages of cone-beam computed tomography (CBCT) is
      the possibility of obtaining images of conventional lateral cephalograms derived
      from partial or complete reconstruction of facial images. OBJECTIVE: This study
      aimed at comparing full face, right and left hemifacial CBCT cephalograms of
      orthodontic patients without clinical facial asymmetry. METHODS: The sample
      comprised nine clinically symmetrical patients who had pretreatment full face
      CBCT. The CBCTs were reconstructed so as to obtain full face, right and left
      hemifacial cephalograms. Two observers, at two different times, obtained linear
      and angular measurements for the images using Dolphin 3D software. Dependent and
      independent t-tests were used to assess the reproducibility of measurements.
      Analysis of Variance and Kruskal-Wallis tests were used to compare the variables
      obtained in the CBCT derived cephalometric views. RESULTS: There was good
      reproducibility for CBCT scans and no statistically significant differences
      between measurements of full face, right and left hemifacial CBCT scans.
      CONCLUSIONS: Cephalometric measurements in full face, right and left hemifacial
      CBCT scans in clinically symmetrical patients are similar.

PMID- 25992993
TI  - Web-based evaluation of experts' opinions on impacted maxillary canines forced
      eruption using CBCT.
AB  - AIM: This study aims at examining the difficulty in performing forced eruption of
      impacted maxillary canines, using CBCT information and according to experienced
      orthodontist's opinion. The second aim was to find the most important factors
      related to this decision. METHODS: Based on a careful literature review on
      impacted maxillary canines, ten main factors were selected to assess difficulties
      associated with impacted teeth. Thirty six consecutive patients with 50 impacted
      maxillary canines were examined and variables were measured for each impacted
      tooth using Dolphin 3D software. Ten orthodontists assessed the radiographs of
      teeth and provided their opinion on the difficulty in bringing impacted teeth
      into occlusion named subjective degree of difficulty (SDD). The correlation
      established between mean SDD of each tooth and measured variables were analyzed
      by means of linear regression. RESULTS: Mean SDD was 6.45 +/- 1.22 for all 50
      teeth. Linear regression showed a high coefficient of correlation between mean
      SDD and age, dilacerations, vertical height, angulation and horizontal overlap (P
      < 0.05). CONCLUSION: To predict the difficulty of impacted maxillary canines
      forced eruption, according to the opinion of experienced orthodontists, the
      factors age, dilaceration, angulation, overlap and vertical distance from the
      occlusal plane are the most important variables.

PMID- 25992994
TI  - Orthodontic management of bilateral maxillary canine-first premolar transposition
      and bilateral agenesis of maxillary lateral incisors: a case report.
AB  - INTRODUCTION: Maxillary canine-first premolar transposition (Mx.C.P1) is an
      uncommon dental positional anomaly that may create many orthodontic problems from
      both esthetic and functional points of view. OBJECTIVE: In this report we show
      the orthodontic management of a case of Mx.C.P1 associated with bilateral
      maxillary lateral incisor agenesis and unilateral mandibular second premolar
      agenesis METHODS: The patient was treated with a multibracket appliance and the
      extraction of the lower premolar. RESULTS: treatment was completed without the
      need for any prosthetic replacement.

PMID- 25992995
TI  - Angle Class II, subdivision, with agenesis of mandibular second molars and
      extrusion of maxillary second molars.
AB  - This clinical case reports the treatment of an Angle Class II malocclusion in a
      young woman with a balanced face affected by agenesis of second and third
      mandibular molars and subsequent extrusion of second maxillary molars. The
      atypical and peculiar occlusal anomaly led to individualized treatment proposed
      in order to normalize dental malpositions, with subsequent rehabilitation of
      edentulous areas by means of a multidisciplinary approach. This case was
      presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics
      (BBO) in partial fulfillment of the requirements for obtaining the title of
      certified by the BBO. 

PMID- 25992996
TI  - Scientific use of the finite element method in Orthodontics.
AB  - INTRODUCTION: The finite element method (FEM) is an engineering resource applied
      to calculate the stress and deformation of complex structures, and has been
      widely used in orthodontic research. With the advantage of being a non-invasive
      and accurate method that provides quantitative and detailed data on the
      physiological reactions possible to occur in tissues, applying the FEM can
      anticipate the visualization of these tissue responses through the observation of
      areas of stress created from applied orthodontic mechanics. OBJECTIVE: This
      article aims at reviewing and discussing the stages of the finite element method
      application and its applicability in Orthodontics. RESULTS: FEM is able to
      evaluate the stress distribution at the interface between periodontal ligament
      and alveolar bone, and the shifting trend in various types of tooth movement when
      using different types of orthodontic devices. Therefore, it is necessary to know
      specific software for this purpose. CONCLUSIONS: FEM is an important experimental
      method to answer questions about tooth movement, overcoming the disadvantages of
      other experimental methods.

PMID- 25992997
TI  - Epidemiological Study of Mammary Tumors in Female Dogs Diagnosed during the
      Period 2002-2012: A Growing Animal Health Problem.
AB  - Epidemiological studies enable us to analyze disease behavior, define risk
      factors and establish fundamental prognostic criteria, with the purpose of
      studying different types of diseases. The aim of this study was to determine the
      epidemiological characteristics of canine mammary tumors diagnosed during the
      period 2002-2012. The study was based on a retrospective study consisting of
      1,917 biopsies of intact dogs that presented mammary gland lesions. Biopsies were
      sent to the Department of Pathology FMVZ-UNAM diagnostic service. The annual
      incidence of mammary tumors was 16.8%: 47.7% (benign) and 47.5% (malignant). The
      highest number of cases was epithelial, followed by mixed tumors. The most
      commonly diagnosed tumors were tubular adenoma, papillary adenoma, tubular
      carcinoma, papillary carcinoma, solid carcinoma, complex carcinoma and
      carcinosarcoma. Pure breeds accounted for 80% of submissions, and the Poodle,
      Cocker Spaniel and German Shepherd were consistently affected. Adult female dogs
      (9 to 12 years old) were most frequently involved, followed by 5- to 8-year-old
      females. Some association between breeds with histological types of malignant
      tumors was observed, but no association was found between breeds and BN. Mammary
      tumors in intact dogs had a high incidence. Benign and malignant tumors had
      similar frequencies, with an increase in malignant tumors in the past four years
      of the study. Epithelial tumors were more common, and the most affected were old
      adult females, purebreds and small-sized dogs. Mammary tumors in dogs are an
      important animal health problem that needs to be solved by improving veterinary
      oncology services in Mexico. 

PMID- 25992998
TI  - A statistical skull geometry model for children 0-3 years old.
AB  - Head injury is the leading cause of fatality and long-term disability for
      children. Pediatric heads change rapidly in both size and shape during growth,
      especially for children under 3 years old (YO). To accurately assess the head
      injury risks for children, it is necessary to understand the geometry of the
      pediatric head and how morphologic features influence injury causation within the
      0-3 YO population. In this study, head CT scans from fifty-six 0-3 YO children
      were used to develop a statistical model of pediatric skull geometry. Geometric
      features important for injury prediction, including skull size and shape, skull
      thickness and suture width, along with their variations among the sample
      population, were quantified through a series of image and statistical analyses.
      The size and shape of the pediatric skull change significantly with age and head
      circumference. The skull thickness and suture width vary with age, head
      circumference and location, which will have important effects on skull stiffness
      and injury prediction. The statistical geometry model developed in this study can
      provide a geometrical basis for future development of child anthropomorphic test
      devices and pediatric head finite element models. 

PMID- 25992999
TI  - Direct 4D PET MLEM reconstruction of parametric images using the simplified
      reference tissue model with the basis function method for [11C]raclopride.
AB  - This work assesses the one-step late maximum likelihood expectation maximization
      (OSL-MLEM) 4D PET reconstruction algorithm for direct estimation of parametric
      images from raw PET data when using the simplified reference tissue model with
      the basis function method (SRTM-BFM) for the kinetic analysis. To date, the OSL
      MLEM method has been evaluated using kinetic models based on two-tissue
      compartments with an irreversible component. We extend the evaluation of this
      method for two-tissue compartments with a reversible component, using SRTM-BFM on
      simulated 3D + time data sets (with use of [(11)C]raclopride time-activity curves
      from real data) and on real data sets acquired with the high resolution research
      tomograph. The performance of the proposed method is evaluated by comparing voxel
      level binding potential (BPND) estimates with those obtained from conventional
      post-reconstruction kinetic parameter estimation. For the commonly chosen number
      of iterations used in practice, our results show that for the 3D + time
      simulation, the direct method delivers results with lower (%)RMSE at the normal
      count level (decreases of 9-10 percentage points, corresponding to a 38-44%
      reduction), and also at low count levels (decreases of 17-21 percentage points,
      corresponding to a 26-36% reduction). As for the real 3D data set, the results
      obtained follow a similar trend, with the direct reconstruction method offering a
      21% decrease in (%)CV compared to the post reconstruction method at low count
      levels. Thus, based on the results presented herein, using the SRTM-BFM kinetic
      model in conjunction with the OSL-MLEM direct 4D PET MLEM reconstruction method
      offers an improvement in performance when compared to conventional post
      reconstruction methods.

PMID- 25993000
TI  - High Doses of Daunorubicin during Induction Therapy of Newly Diagnosed Acute
      Myeloid Leukemia: A Systematic Review and Meta-Analysis of Prospective Clinical
      Trials.
AB  - The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute
      myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting
      results concerning the efficacy of high or low doses of daunorubicin to induction
      chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was
      conducted to resolve this controversial issue. We compared the efficacy and
      safety of high doses of daunorubicin (HD-DNR) and traditional low doses of
      daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly
      diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were
      retrieved and six randomized controlled trials were analyzed. The primary
      outcomes were overall survival (OS), disease-free survival (DFS), and event-free
      survival (EFS). The secondary outcomes included complete remission (CR), relapse,
      and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD
      DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18],
      p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI
      [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no
      statistically significant differences in any other outcomes between HD-DNR and
      IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly
      improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse
      and toxicity. 

PMID- 25993001
TI  - Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the
      Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular
      Dynamics Simulations.
AB  - The fragment 106-126 of prion protein exhibits similar properties to full-length
      prion. Experiments have shown that the A117V mutation enhances the aggregation of
      PrP106-126, while the H111S mutation abolishes the assembly. However, the
      mechanism of the change in the aggregation behavior of PrP106-126 upon the two
      mutations is not fully understood. In this study, replica exchange molecular
      dynamics simulations were performed to investigate the conformational ensemble of
      the WT PrP106-126 and its two mutants A117V and H111S. The obtained results
      indicate that the three species are all intrinsically disordered but they have
      distinct morphological differences. The A117V mutant has a higher propensity to
      form beta-hairpin structures than the WT, while the H111S mutant has a higher
      population of helical structures. Furthermore, the A117V mutation increases the
      hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation
      reduces the exposure of hydrophobic residues. It can be concluded that the
      difference in populations of beta-hairpin structures and the change of
      hydrophobic solvent accessible areas may induce the different aggregation
      behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the
      two mutations have contrary effects on the aggregation of PrP106-126 is very
      meaningful for further elucidation of the mechanism underlying aggregation and
      design of inhibitor against aggregation process. 

PMID- 25993002
TI  - Location is everything: evaluating the effects of terrestrial and marine resource
      subsidies on an estuarine bivalve.
AB  - Estuaries are amongst the world's most productive ecosystems, lying at the
      intersection between terrestrial and marine environments. They receive
      substantial inputs from adjacent landscapes but the importance of resource
      subsidies is not well understood. Here, we test hypotheses for the effects of
      both terrestrial- and salmon-derived resource subsidies on the diet (inferred
      from stable isotopes of muscle tissue), size and percent nitrogen of the soft
      shell clam (Mya arenaria), a sedentary estuarine consumer. We examine how these
      relationships shift across natural gradients among 14 estuaries that vary in
      upstream watershed size and salmon density on the central coast of British
      Columbia, Canada. We also test how assimilation and response to subsidies vary at
      smaller spatial scales within estuaries. The depletion and enrichment of stable
      isotope ratios in soft-shell clam muscle tissue correlated with increasing
      upstream watershed size and salmon density, respectively. The effects of
      terrestrial- and salmon-derived subsidies were also strongest at locations near
      stream outlets. When we controlled for age of individual clams, there were larger
      individuals with higher percent nitrogen content in estuaries below larger
      watersheds, though this effect was limited to the depositional zones below river
      mouths. Pink salmon exhibited a stronger effect on isotope ratios of clams than
      chum salmon, which could reflect increased habitat overlap as spawning pink
      salmon concentrate in lower stream reaches, closer to intertidal clam beds.
      However, there were smaller clams in estuaries that had higher upstream pink
      salmon densities, possibly due to differences in habitat requirements. Our study
      highlights the importance of upstream resource subsidies to this bivalve species,
      but that individual responses to subsidies can vary at smaller scales within
      estuaries. 

PMID- 25993003
TI  - Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non
      Gastric H+/K+-ATPases.
AB  - The mechanism by which pancreas secretes high HCO3- has not been fully resolved.
      This alkaline secretion, formed in pancreatic ducts, can be achieved by
      transporting HCO3- from serosa to mucosa or by moving H+ in the opposite
      direction. The aim of the present study was to determine whether H+/K+-ATPases
      are expressed and functional in human pancreatic ducts and whether proton pump
      inhibitors (PPIs) have effect on those. Here we show that the gastric HKalpha1
      and HKbeta subunits (ATP4A; ATP4B) and non-gastric HKalpha2 subunits (ATP12A) of
      H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar
      localizations in duct cell monolayers (Capan-1) and human pancreas, and notably
      the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs
      inhibited recovery of intracellular pH from acidosis. Furthermore, in rats
      treated with PPIs, pancreatic secretion was inhibited but concentrations of major
      ions in secretion follow similar excretory curves in control and PPI treated
      animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this
      study calls for a revision of the basic model for HCO3- secretion. We propose
      that proton transport is driving secretion, and that in addition it may provide a
      protective pH buffer zone and K+ recirculation. Furthermore, it seems relevant to
      re-evaluate whether PPIs should be used in treatment therapies where pancreatic
      functions are already compromised. 

PMID- 25993004
TI  - Metapopulation persistence in random fragmented landscapes.
AB  - Habitat destruction and land use change are making the world in which natural
      populations live increasingly fragmented, often leading to local extinctions.
      Although local populations might undergo extinction, a metapopulation may still
      be viable as long as patches of suitable habitat are connected by dispersal, so
      that empty patches can be recolonized. Thus far, metapopulations models have
      either taken a mean-field approach, or have modeled empirically-based, realistic
      landscapes. Here we show that an intermediate level of complexity between these
      two extremes is to consider random landscapes, in which the patches of suitable
      habitat are randomly arranged in an area (or volume). Using methods borrowed from
      the mathematics of Random Geometric Graphs and Euclidean Random Matrices, we
      derive a simple, analytic criterion for the persistence of the metapopulation in
      random fragmented landscapes. Our results show how the density of patches, the
      variability in their value, the shape of the dispersal kernel, and the
      dimensionality of the landscape all contribute to determining the fate of the
      metapopulation. Using this framework, we derive sufficient conditions for the
      population to be spatially localized, such that spatially confined clusters of
      patches act as a source of dispersal for the whole landscape. Finally, we show
      that a regular arrangement of the patches is always detrimental for persistence,
      compared to the random arrangement of the patches. Given the strong parallel
      between metapopulation models and contact processes, our results are also
      applicable to models of disease spread on spatial networks. 

PMID- 25993005
TI  - How Has the Age-Related Process of Overweight or Obesity Development Changed over
      Time? Co-ordinated Analyses of Individual Participant Data from Five United
      Kingdom Birth Cohorts.
AB  - BACKGROUND: There is a paucity of information on secular trends in the age
      related process by which people develop overweight or obesity. Utilizing
      longitudinal data in the United Kingdom birth cohort studies, we investigated
      shifts over the past nearly 70 years in the distribution of body mass index (BMI)
      and development of overweight or obesity across childhood and adulthood. METHODS
      AND FINDINGS: The sample comprised 56,632 participants with 273,843 BMI
      observations in the 1946 Medical Research Council National Survey of Health and
      Development (NSHD; ages 2-64 years), 1958 National Child Development Study (NCDS;
      7-50), 1970 British Cohort Study (BCS; 10-42), 1991 Avon Longitudinal Study of
      Parents and Children (ALSPAC; 7-18), or 2001 Millennium Cohort Study (MCS; 3-11).
      Growth references showed a secular trend toward positive skewing of the BMI
      distribution at younger ages. During childhood, the 50th centiles for all studies
      lay in the middle of the International Obesity Task Force normal weight range,
      but during adulthood, the age when a 50th centile first entered the overweight
      range (i.e., 25-29.9 kg/m2) decreased across NSHD, NCDS, and BCS from 41 to 33 to
      30 years in males and 48 to 44 to 41 years in females. Trajectories of overweight
      or obesity showed that more recently born cohorts developed greater probabilities
      of overweight or obesity at younger ages. Overweight or obesity became more
      probable in NCDS than NSHD in early adulthood, but more probable in BCS than NCDS
      and NSHD in adolescence, for example. By age 10 years, the estimated
      probabilities of overweight or obesity in cohorts born after the 1980s were 2-3
      times greater than those born before the 1980s (e.g., 0.229 [95% CI 0.219-0.240]
      in MCS males; 0.071 [0.065-0.078] in NSHD males). It was not possible to (1)
      model separate trajectories for overweight and obesity, because there were few
      obesity cases at young ages in the earliest-born cohorts, or (2) consider ethnic
      minority groups. The end date for analyses was August 2014. CONCLUSIONS: Our
      results demonstrate how younger generations are likely to accumulate greater
      exposure to overweight or obesity throughout their lives and, thus, increased
      risk for chronic health conditions such as coronary heart disease and type 2
      diabetes mellitus. In the absence of effective intervention, overweight and
      obesity will have severe public health consequences in decades to come.

PMID- 25993006
TI  - Minimally invasive electro-magnetic navigational bronchoscopy-integrated near
      infrared-guided sentinel lymph node mapping in the porcine lung.
AB  - BACKGROUND: The use of near-infrared (NIR) fluorescence imaging with indocyanine
      green (ICG) for sentinel lymph node (SN) mapping has been investigated in lung
      cancer; however, this has not been fully adapted for minimally invasive surgery
      (MIS). The aim of our study was to develop a minimally invasive SN mapping
      integrating pre-operative electro-magnetic navigational bronchoscopy (ENB)-guided
      transbronchial ICG injection and intraoperative NIR thoracoscopic imaging.
      METHODS: A NIR thoracoscope was used to visualize ICG fluorescence. ICG solutions
      in a 96-well plate and ex vivo porcine lungs were examined to optimize ICG
      concentrations and injection volumes. Transbronchial ICG injection (n=4) was
      assessed in comparison to a traditional transpleural approach (n=3), where after
      thoracotomy an ICG solution (100 MUL at 100 MUg/mL) was injected into the porcine
      right upper lobe for SN identification. For further translation into clinical
      use, transbronchial ICG injection prior to thoracotomy followed by NIR
      thoracoscopic imaging was validated (n=3). ENB was used for accurate targeting in
      two pigs with a pseudo-tumor. RESULTS: The ICG fluorescence at 10 MUg/mL was the
      brightest among various concentrations, unchanged by the distance between the
      thoracoscope and ICG solutions. Injected ICG of no more than 500MU L showed a
      localized fluorescence area. All 7 pigs showed a bright paratracheal lymph node
      within 15 minutes post-injection, with persistent fluorescence for 60 minutes.
      The antecedent transbronchial ICG injection succeeded in SN identification in all
      3 cases at the first thoracoscopic inspection within 20 minutes post-injection.
      The ENB system allowed accurate ICG injection surrounding the pseudo-tumors.
      CONCLUSIONS: ENB-guided ICG injection followed by NIR thoracoscopy was
      technically feasible for SN mapping in the porcine lung. This promising platform
      may be translated into human clinical trials and is suited for MIS.

PMID- 25993007
TI  - Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of
      FOXO3 Variations.
AB  - BACKGROUND: Glucose homeostasis is a trait of healthy ageing and is crucial to
      the elderly, but less consideration has been given to the age composition in most
      studies involving genetics and hyperglycemia. METHODS: Seven variants in FOXO3
      were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 +/-
      3.6, 45.9 +/- 8.2 and 46.8 +/- 10.3, respectively) to compare the contribution of
      FOXO3 to fasting hyperglycemia (FH) between long-lived individuals (LLI, aged
      over 90 years) and middle-aged subjects (aged from 35-65 years). RESULTS: A
      different genetic predisposition of FOXO3 alleles to FH was observed between LLI
      and both of two middle-aged cohorts. In the LLI cohort, the longevity beneficial
      alleles of three variants with the haplotype "AGGC" in block 1 were significantly
      protective to FH, fasting glucose, hemoglobin A1C and HOMA-IR. Notably, combining
      multifactor dimensionality reduction and logistic regression, we identified a
      significant 3-factor interaction model (rs2802288, rs2802292 and moderate
      physical activity) associated with lower FH risk. However, not all of the
      findings were replicated in the two middle-aged cohorts. CONCLUSION: Our data
      provides a novel insight into the inconsistent genetic determinants between
      middle-aged and LLI subjects. FOXO3 might act as a shared genetic predisposition
      to hyperglycemia and lifespan.

PMID- 25993008
TI  - Studies of Antibiotic Resistance of Beta-Lactamase Bacteria under Different
      Nutrition Limitations at the Single-Cell Level.
AB  - Drug resistance involves many biological processes, including cell growth, cell
      communication, and cell cooperation. In the last few decades, bacterial drug
      resistance studies have made substantial progress. However, a major limitation of
      the traditional resistance study still exists: most of the studies have
      concentrated on the average behavior of enormous amounts of cells rather than
      surveying single cells with different phenotypes or genotypes. Here, we report
      our study of beta-lactamase bacterial drug resistance in a well-designed
      microfluidic device, which allows us to conduct more controllable experiments,
      such as controlling the nutrient concentration, switching the culture media,
      performing parallel experiments, observing single cells, and acquiring time-lapse
      images. By using GFP as a beta-lactamase indicator and acquiring time-lapse
      images at the single-cell level, we observed correlations between the bacterial
      heterogeneous phenotypes and their behavior in different culture media. The
      feedback loop between the growth rate and the beta-lactamase production suggests
      that the beta-lactamase bacteria are more resistant in a rich medium than in a
      relatively poor medium. In the poorest medium, the proportion of dormant cells
      may increase, which causes a lower death rate in the same generation. Our work
      may contribute to assaying the antibiotic resistance of pathogenic bacteria in
      heterogeneous complex media. 

PMID- 25993009
TI  - An analytical model of leakage neutron equivalent dose for passively-scattered
      proton radiotherapy and validation with measurements.
AB  - Exposure to stray neutrons increases the risk of second cancer development after
      proton therapy. Previously reported analytical models of this exposure were
      difficult to configure and had not been investigated below 100 MeV proton energy.
      The purposes of this study were to test an analytical model of neutron equivalent
      dose per therapeutic absorbed dose  at 75 MeV and to improve the model by
      reducing the number of configuration parameters and making it continuous in
      proton energy from 100 to 250 MeV. To develop the analytical model, we used
      previously published H/D values in water from Monte Carlo simulations of a
      general-purpose beamline for proton energies from 100 to 250 MeV. We also
      configured and tested the model on in-air neutron equivalent doses measured for a
      75 MeV ocular beamline. Predicted H/D values from the analytical model and Monte
      Carlo agreed well from 100 to 250 MeV (10% average difference). Predicted H/D
      values from the analytical model also agreed well with measurements at 75 MeV
      (15% average difference). The results indicate that analytical models can give
      fast, reliable calculations of neutron exposure after proton therapy. This
      ability is absent in treatment planning systems but vital to second cancer risk
      estimation. 

PMID- 25993010
TI  - Image-Guided Radiotherapy Using a Modified Industrial Micro-CT for Preclinical
      Applications.
AB  - PURPOSE/OBJECTIVE: Although radiotherapy is a key component of cancer treatment,
      its implementation into pre-clinical in vivo models with relatively small target
      volumes is frequently omitted either due to technical complexity or expected side
      effects hampering long-term observational studies. We here demonstrate how an
      affordable industrial micro-CT can be converted into a small animal IGRT device
      at very low costs. We also demonstrate the proof of principle for the case of
      partial brain irradiation of mice carrying orthotopic glioblastoma implants.
      METHODS/MATERIALS: A commercially available micro-CT originally designed for non
      destructive material analysis was used. It consists of a CNC manipulator, a
      transmission X-ray tube (10-160 kV) and a flat-panel detector, which was used
      together with custom-made steel collimators (1-5 mm aperture size). For radiation
      field characterization, an ionization chamber, water-equivalent slab phantoms and
      radiochromic films were used. A treatment planning tool was implemented using a
      C++ application. For proof of principle, NOD/SCID/gammac(-/-) mice were
      orthotopically implanted with U87MG high-grade glioma cells and irradiated using
      the novel setup. RESULTS: The overall symmetry of the radiation field at 150 kV
      was 1.04 +/- 0.02%. The flatness was 4.99 +/- 0.63% and the penumbra widths were
      between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from
      1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve
      along the central axis followed a typical shape of keV photons. Dose rates
      measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator
      aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well
      and resulted in central tumor necrosis consistent with therapeutic efficacy.
      CONCLUSION: A conventional industrial micro-CT can be easily modified to allow
      effective small animal IGRT even of critical target volumes such as the brain.

PMID- 25993011
TI  - Toddaculin, Isolated from of Toddalia asiatica (L.) Lam., Inhibited
      Osteoclastogenesis in RAW 264 Cells and Enhanced Osteoblastogenesis in MC3T3-E1
      Cells.
AB  - Osteoporosis with bone loss is widely recognized as a major health problem. Bone
      homeostasis is maintained by balancing bone formation and bone resorption. The
      imbalance caused by increased bone resorption over bone formation can lead to
      various bone-related diseases such as osteoporosis and rheumatoid arthritis.
      Osteoclasts are the principal cells responsible for bone resorption and the main
      targets of anti-resorptive therapies. However, excessive inhibition of osteoclast
      differentiation may lead to inhibition of osteoblast differentiation. Therefore,
      it is important to screen for new compounds capable of inhibiting bone resorption
      and enhancing bone formation. Toddalia asiatica (L.) Lam. has been utilized
      traditionally for medicinal purposes such as the treatment of rheumatism.
      Currently, the extract is considered to be a good source of pharmacological
      agents for the treatment of bone-related diseases, but the active compounds have
      yet to be identified. We investigated whether toddaculin, derived from Toddalia
      asiatica (L.) Lam., affects both processes by inhibiting bone resorption and
      enhancing bone formation. Towards this end, we used pre-osteoclastic RAW 264
      cells and pre-osteoblastic MC3T3-E1 cells. We found that toddaculin not only
      inhibited the differentiation of osteoclasts via activation of the NF-kappaB, ERK
      1/2, and p38 MAPK signaling pathways, but it also induced differentiation and
      mineralization of osteoblasts by regulating differentiation factors. Thus,
      toddaculin might be beneficial for the prevention and treatment of osteoporosis. 

PMID- 25993014
TI  - Biocompatibility of poly(2-alkyl-2-oxazoline) brush surfaces for adherent lung
      cell lines.
AB  - Development of synthetic surfaces that are highly reproducible and biocompatible
      for in vitro cell culture offers potential for development of improved models for
      studies of cellular physiology and pathology. They may also be useful in tissue
      engineering by removal of the need for biologically-derived components such as
      extracellular matrix proteins. We synthesised four types of 2-alkyl-2-oxazoline
      polymers ranging from the hydrophilic poly(2-methyl-2-oxazoline) to the
      hydrophobic poly(2-n-butyl-2-oxazoline). The polymers were terminated using amine
      functionalised glass coverslips, enabling the synthetic procedure to be
      reproducible and scaleable. The polymer-coated glass slides were tested for
      biocompatibility using human epithelial (16HBE14o-) and fibroblastic (MRC5) cell
      lines. Differences in adhesion and motility of the two cell types was observed,
      with the poly(2-isopropyl-2-oxazoline) polymer equally supporting the growth of
      both cell types, whereas poly(2-n-butyl-2-oxazoline) showed selectivity for
      fibroblast growth. In summary, 2-alkyl-2-oxazoline polymers may be a useful tool
      for building in vitro model cell culture models with preferential adhesion of
      specific cell types. 

PMID- 25993013
TI  - Dissimilar Regulation of Antimicrobial Proteins in the Midgut of Spodoptera
      exigua Larvae Challenged with Bacillus thuringiensis Toxins or Baculovirus.
AB  - Antimicrobial peptides (AMPs) and lysozymes are the main effectors of the insect
      immune system, and they are involved in both local and systemic responses. Among
      local responses, midgut immune reaction plays an important role in fighting
      pathogens that reach the insect body through the oral route, as do many
      microorganisms used in pest control. Under this point of view, understanding how
      insects defend themselves locally during the first phases of infections caused by
      food-borne pathogens is important to further improve microbial control
      strategies. In the present study, we analyzed the transcriptional response of
      AMPs and lysozymes in the midgut of Spodoptera exigua (Lepidoptera: Noctuidae), a
      polyphagous pest that is commonly controlled by products based on Bacillus
      thuringiensis (Bt) or baculovirus. First, we comprehensively characterized the
      transcripts encoding AMPs and lysozymes expressed in S. exigua larval midgut,
      identifying 35 transcripts that represent the S. exigua arsenal against microbial
      infection. Secondly, we analyzed their expression in the midgut after ingestion
      of sub-lethal doses of two different pore-forming B. thuringiensis toxins, Cry1Ca
      and Vip3Aa, and the S. exigua nucleopolyhedrovirus (SeMNPV). We observed that
      both Bt toxins triggered a similar, wide and in some cases high transcriptional
      activation of genes encoding AMPs and lysozymes, which was not reflected in the
      activation of the classical systemic immune-marker phenoloxidase in hemolymph.
      Baculovirus ingestion resulted in the opposed reaction: Almost all transcripts
      coding for AMPs and lysozymes were down-regulated or not induced 96 hours post
      infection. Our results shed light on midgut response to different virulence
      factors or pathogens used nowadays as microbial control agents and point out the
      importance of the midgut immune response contribution to the larval immunity. 

PMID- 25993015
TI  - Polymeric microparticles for sustained and local delivery of antiCD40 and
      antiCTLA-4 in immunotherapy of cancer.
AB  - This study investigated the feasibility of the use of polymeric microparticles
      for sustained and local delivery of immunomodulatory antibodies in immunotherapy
      of cancer. Local delivery of potent immunomodulatory antibodies avoids unwanted
      systemic side effects while retaining their anti-tumor effects. Microparticles
      based on poly(lactic-co-hydroxymethyl-glycolic acid) (pLHMGA) and loaded with two
      distinct types of immunomodulatory antibodies (CTLA-4 antibody blocking
      inhibitory receptors on T cells or CD40 agonistic antibody stimulating dendritic
      cells) were prepared by double emulsion solvent evaporation technique. The
      obtained particles had a diameter of 12-15 MUm to avoid engulfment by phagocytes
      and were slightly porous as shown by SEM analysis. The loading efficiency of the
      antibodies in the microparticles was >85%. The in vitro release profile of
      antiCD40 and antiCTLA-4 from microparticles showed a burst release of about 20%
      followed by a sustained release of the content up to 80% of the loading in around
      30 days. The therapeutic efficacy of the microparticulate formulations was
      studied in colon carcinoma tumor model (MC-38). Mice bearing subcutaneous MC-38
      tumors were treated with the same dose of immunomodulatory antibodies formulated
      either in incomplete Freund's adjuvant (IFA) or in microparticles. The antibody
      loaded microparticles showed comparable therapeutic efficacy to the IFA
      formulation with no local adverse effects. The biodegradable microparticles were
      fully resorbed in vivo and no remnants of inflammatory depots as observed with
      IFA were present in the cured mice. Moreover the microparticles exhibited lower
      antibody serum levels in comparison with IFA formulations which lowers the
      probability of systemic adverse effects. In conclusion, pLHMGA microparticles are
      excellent delivery systems in providing long-lasting and non-toxic antibody
      therapy for immunotherapy of cancer. 

PMID- 25993017
TI  - Persistence with denosumab therapy among osteoporotic women in the Canadian
      patient-support program.
AB  - OBJECTIVE: The objective of this study was to evaluate persistence with denosumab
      among postmenopausal women with osteoporosis participating in the Canadian
      patient-support program (ProVital * ). Denosumab is an injectable therapeutic
      option for osteoporosis that is administered subcutaneously every 6 months.
      METHODS: ProVital, a support program in which patients voluntarily enroll,
      provides next injection reminder calls and educational material. A retrospective
      database analysis of patient self-reported data was conducted among osteoporotic
      women aged >=50 who enrolled in the ProVital program and received their first
      denosumab injection between August 2010 and June 2011. To achieve 12 month
      persistence patients had to receive at least two denosumab injections, and to
      achieve 24 month persistence patients had to receive at least four denosumab
      injections, with consecutive injections no more than 6 months + 8 weeks apart.
      Logistic regression analysis was used to identify predictors of persistence.
      RESULTS: A total of 1676 patients (mean age 74 years) were included. The 12 month
      persistence with denosumab was 81.6% (1367/1676 patients), and the 24 month
      persistence was 59.1% (991/1676 patients). Characteristics associated with both
      12 and 24 month persistence were possession of private medication insurance and
      residence in Quebec. Additionally, age greater than 75, previous postmenopausal
      osteoporosis medication use, and fracture were associated with 24 month
      persistence. LIMITATIONS: Patient enrollment in the program was voluntary, so
      there may be selection bias for the patient population included in this study.
      Also, this study did not have a control group of patients who were not enrolled
      in a patient support program. CONCLUSIONS: The persistence with denosumab among
      patients enrolled in the program was higher than historical persistence with oral
      bisphosphonates, and similar to persistence of patients in an education program
      taking teriparatide, patients taking bisphosphonates in a pharmaceutical care
      program, and two observational studies of denosumab.

PMID- 25993016
TI  - Convergent evolution at the gametophytic self-incompatibility system in Malus and
      Prunus.
AB  - S-RNase-based gametophytic self-incompatibility (GSI) has evolved once before the
      split of the Asteridae and Rosidae. This conclusion is based on the phylogenetic
      history of the S-RNase that determines pistil specificity. In Rosaceae, molecular
      characterizations of Prunus species, and species from the tribe Pyreae (i.e.,
      Malus, Pyrus, Sorbus) revealed different numbers of genes determining S-pollen
      specificity. In Prunus only one pistil and pollen gene determine GSI, while in
      Pyreae there is one pistil but multiple pollen genes, implying different
      specificity recognition mechanisms. It is thus conceivable that within Rosaceae
      the genes involved in GSI in the two lineages are not orthologous but possibly
      paralogous. To address this hypothesis we characterised the S-RNase lineage and S
      pollen lineage genes present in the genomes of five Rosaceae species from three
      genera: M. * domestica (apple, self-incompatible (SI); tribe Pyreae), P. persica
      (peach, self-compatible (SC); Amygdaleae), P. mume (mei, SI; Amygdaleae),
      Fragaria vesca (strawberry, SC; Potentilleae), and F. nipponica (mori-ichigo, SI;
      Potentilleae). Phylogenetic analyses revealed that the Malus and Prunus S-RNase
      and S-pollen genes belong to distinct gene lineages, and that only Prunus S-RNase
      and SFB-lineage genes are present in Fragaria. Thus, S-RNase based GSI system of
      Malus evolved independently from the ancestral system of Rosaceae. Using
      expression patterns based on RNA-seq data, the ancestral S-RNase lineage gene is
      inferred to be expressed in pistils only, while the ancestral S-pollen lineage
      gene is inferred to be expressed in tissues other than pollen. 

PMID- 25993018
TI  - A Paramedic-staffed Helicopter Emergency Medical Service's Response to Winch
      Missions in Victoria, Australia.
AB  - Winching emergency medical care providers from a helicopter to the scene enables
      treatment of patients in otherwise inaccessible locations, but is not without
      risks. The objective of this study was to define characteristics of winch
      missions undertaken by Intensive Care Flight Paramedics (ICFP) in Victoria,
      Australia with a focus on extraction methods and clinical care delivered at the
      scene. A retrospective data analysis was performed to identify all winch missions
      between November 2010 and March 2014. Demographic data, winch characteristics,
      physiological parameters, and interventions undertaken on scene by the ICFP were
      extracted. Out of 5,003 missions in the study period, 125 were identified as
      winch operations. Winter missions were significantly less frequent than those of
      any other season. Patients were predominantly male (78.4%) and had a mean age of
      38 years (+/-17.6). A total of 109 (87.2%) patients were identified as
      experiencing trauma with a mean Revised Trauma Score of 7.5288, and isolated limb
      fractures were the most frequently encountered injury. Falls and vehicle-related
      trauma were the most common mechanisms of injury. The total median scene duration
      was 49 minutes (IQR 23-91). Sixty-three patients (50.4%) were extracted using a
      stretcher, 45 (36.0%) using a hypothermic strop, and 6 (4.8%) via normal rescue
      strop. Eleven patients (8.8%) were not winched to the helicopter. Vascular access
      (38.4%), analgesia (44.0%), and anti-emetic administration (28.8%) were the most
      frequent clinical interventions. Forty-nine patients (39.2%) did not receive any
      clinical intervention prior to winch extraction. Winch operations in Victoria,
      Australia consisted predominantly of patients with minor to moderate traumatic
      injuries. A significant proportion of patients did not require any clinical
      treatment prior to winching, and among those who did, analgesia was the most
      frequent intervention. Advanced medical procedures were rarely required prior to
      winch extraction.

PMID- 25993019
TI  - Physical Sensing of Surface Properties by Microswimmers--Directing Bacterial
      Motion via Wall Slip.
AB  - Bacteria such as Escherichia coli swim along circular trajectories adjacent to
      surfaces. Thereby, the orientation (clockwise, counterclockwise) and the
      curvature depend on the surface properties. We employ mesoscale hydrodynamic
      simulations of a mechano-elastic model of E. coli, with a spherocylindrical body
      propelled by a bundle of rotating helical flagella, to study quantitatively the
      curvature of the appearing circular trajectories. We demonstrate that the cell is
      sensitive to nanoscale changes in the surface slip length. The results are
      employed to propose a novel approach to directing bacterial motion on striped
      surfaces with different slip lengths, which implies a transformation of the
      circular motion into a snaking motion along the stripe boundaries. The
      feasibility of this approach is demonstrated by a simulation of active Brownian
      rods, which also reveals a dependence of directional motion on the stripe width. 

PMID- 25993020
TI  - Serotonin 1B Receptor Gene (HTR1B) Methylation as a Risk Factor for Callous
      Unemotional Traits in Antisocial Boys.
AB  - The serotonin system is thought to play a role in the aetiology of callous
      unemotional (CU) traits in children. Previous research identified a functional
      single nucleotide polymorphism (SNP) from the promoter region of the serotonin 1B
      receptor gene as being associated with CU traits in boys with antisocial
      behaviour problems. This research tested the hypothesis that CU traits are
      associated with reduced methylation of the promoter region of the serotonin 1B
      receptor gene due to the influence of methylation on gene expression.
      Participants (N = 117) were boys with antisocial behaviour problems aged 3-16
      years referred to University of New South Wales Child Behaviour Research Clinics.
      Participants volunteered a saliva sample from which the genotype of a SNP from
      the promoter region of the serotonin 1B receptor gene and the methylation levels
      of 30 CpG sites from 3 CpG regions surrounding the location of this polymorphism
      were assayed. Lower levels of serotonin 1B receptor gene methylation were
      associated with higher levels of CU traits. This relationship, however, was found
      to be moderated by genotype and carried exclusively by two CpG sites for which
      levels of methylation were negatively associated with overall methylation levels
      in this region of the gene. Results provide support to the emerging literature
      that argues for a genetically-driven system-wide alteration in serotonin function
      in the aetiology of CU traits. Furthermore, the results suggest that there may be
      two pathways to CU traits that involve methylation of the serotonin 1B receptor
      gene; one that is driven by a genotypic risk and another that is associated with
      risk for generally increased levels of methylation. Future research that aims to
      replicate and further investigate these results is required. 

PMID- 25993021
TI  - Synthesis of Carboxylate Cp*Zr(IV) Species: Toward the Formation of Novel
      Metallocavitands.
AB  - With the intent of generating metallocavitands isostructural to species
      [(CpZr)3(MU(3)-O)(MU(2)-OH)3(kappaO,O,MU(2)-O2C(R))3](+), the reaction of
      Cp*2ZrCl2 and Cp*ZrCl3 with phenylcarboxylic acids was carried out. Depending on
      the reaction conditions, five new complexes were obtained, which consisted of
      Cp*2ZrCl(kappa(2)-OOCPh) (1), (Cp*ZrCl(kappa(2)-OOCPh))2(MU-kappa(2)-OOCPh)2 (2),
      [(Cp*Zr(kappa(2)-OOCPh))2(MU-kappa(2)-OOCPh)2(MU(2)-OH)2].Et2O (3.Et2O),
      [[Cp*ZrCl2](MU-Cl)(MU-OH)(MU-O2CC6H5)[Cp*Zr]]2(MU-O2CC6H5)2 (4), and
      [Cp*ZrCl4][(Cp*Zr)3(kappa2-OOC(C6H4Br)3(MU3-O)(MU2-Cl)2(MU2-OH)]
      [5](+)[Cp*ZrCl4](-). The structural characterization of the five complexes was
      carried out. Species 3.Et2O exhibits host-guest properties where the diethyl
      ether molecule is included in a cavity formed by two carboxylate moieties. The
      secondary interactions between the cavity and the diethyl ether molecule affect
      the structural parameters of the complex, as demonstrated be the comparison of
      the density functional theory models for 3 and 3.Et2O. Species 5 was shown to be
      isostructural to the [(CpZr)3(MU(3)-O)(MU(2)-OH)3(kappaO,O,MU(2)-O2C(R))3](+)
      metallocavitands. 

PMID- 25993023
TI  - Leflunomide is associated with a higher flare rate compared to methotrexate in
      the treatment of chronic uveitis in juvenile idiopathic arthritis.
AB  - OBJECTIVES: Chronic anterior uveitis is a serious complication of juvenile
      idiopathic arthritis (JIA); disease flares are highly associated with loss of
      vision. Leflunomide (LEF) is used successfully for JIA joint disease but its
      effectiveness in uveitis has not been determined. The aim of this study was to
      determine whether LEF improves flare rates of uveitis in JIA patients compared to
      preceding methotrexate (MTX) therapy. METHOD: A single-centre retrospective study
      of consecutive children with JIA and chronic anterior uveitis was performed. All
      children initially received MTX and were then switched to LEF. Demographic,
      clinical, and laboratory data, dose and duration of MTX and LEF therapy,
      concomitant medications and rate of anterior uveitis flares, as determined by an
      expert ophthalmologist, were obtained. Flare rates were compared using a
      generalized linear mixed model with a negative binomial distribution. RESULTS: A
      total of 15 children were included (80% females, all antinuclear antibody
      positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF
      was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor
      (anti-TNF-alpha) co-medication was given to four children while on MTX. By
      contrast, LEF was combined with anti-TNF-alpha treatment in six children. On MTX,
      JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF
      treatment was associated with a significantly higher flare rate of 0.0607
      flares/month (p = 0.008). CONCLUSIONS: Children with JIA had significantly more
      uveitis flares on LEF compared to MTX despite receiving anti-TNF-alpha co
      medication more frequently. Therefore, LEF may need to be considered less
      effective in controlling chronic anterior uveitis.

PMID- 25993022
TI  - Experimental evolution of an RNA virus in wild birds: evidence for host-dependent
      impacts on population structure and competitive fitness.
AB  - Within hosts, RNA viruses form populations that are genetically and
      phenotypically complex. Heterogeneity in RNA virus genomes arises due to error
      prone replication and is reduced by stochastic and selective mechanisms that are
      incompletely understood. Defining how natural selection shapes RNA virus
      populations is critical because it can inform treatment paradigms and enhance
      control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught
      American crows, house sparrows and American robins to assess how natural
      selection shapes RNA virus populations in ecologically relevant hosts that differ
      in susceptibility to virus-induced mortality. After five sequential passages in
      each bird species, we examined the phenotype and population diversity of WNV
      through fitness competition assays and next generation sequencing. We demonstrate
      that fitness gains occur in a species-specific manner, with the greatest
      replicative fitness gains in robin-passaged WNV and the least in WNV passaged in
      crows. Sequencing data revealed that intrahost WNV populations were strongly
      influenced by purifying selection and the overall complexity of the viral
      populations was similar among passaged hosts. However, the selective pressures
      that control WNV populations seem to be bird species-dependent. Specifically,
      crow-passaged WNV populations contained the most unique mutations (~1.7* more
      than sparrows, ~3.4* more than robins) and defective genomes (~1.4* greater than
      sparrows, ~2.7* greater than robins), but the lowest average mutation frequency
      (about equal to sparrows, ~2.6* lower than robins). Therefore, our data suggest
      that WNV replication in the most disease-susceptible bird species is positively
      associated with virus mutational tolerance, likely via complementation, and
      negatively associated with the strength of selection. These differences in
      genetic composition most likely have distinct phenotypic consequences for the
      virus populations. Taken together, these results reveal important insights into
      how different hosts may contribute to the emergence of RNA viruses. 

PMID- 25993024
TI  - Experimental estimation of migration and transfer of organic substances from
      consumer articles to cotton wipes: Evaluation of underlying mechanisms.
AB  - The aim of this work was to identify the key mechanisms governing transport of
      organic chemical substances from consumer articles to cotton wipes. The results
      were used to establish a mechanistic model to improve assessment of dermal
      contact exposure. Four types of PVC flooring, 10 types of textiles and one type
      of inkjet printed paper were used to establish the mechanisms and model. Kinetic
      extraction studies in methanol demonstrated existence of matrix diffusion and
      indicated the presence of a substance surface layer on some articles.
      Consequently, the proposed substance transfer model considers mechanical
      transport from a surface film and matrix diffusion in an article with a known
      initial total substance concentration. The estimated chemical substance transfer
      values to cotton wipes were comparable to the literature data (relative transfer
      ~ 2%), whereas relative transfer efficiencies from spiked substrates were high (~
      50%). For consumer articles, high correlation (r(2)=0.92) was observed between
      predicted and measured transfer efficiencies, but concentrations were
      overpredicted by a factor of 10. Adjusting the relative transfer from about 50%
      used in the model to about 2.5% removed overprediction. Further studies are
      required to confirm the model for generic use.

PMID- 25993025
TI  - Gene-specific promoter methylation is associated with micronuclei frequency in
      urothelial cells from individuals exposed to organic solvents and paints.
AB  - Sufficient epidemiologic evidence has established an etiologic link between
      bladder cancer risk and occupational exposure as a painter to organic solvents.
      Currently, it remains to be established whether gene-specific promoter
      methylation contributes to bladder cancer development, including by enhancing
      chromosome breakage or loss. We investigated the effect of chronic exposure to
      organic solvents and paints on DNA methylation profiles in the promoter regions
      of four genes (GSTP1, p16(INK4a), APC and CDH1) and micronucleus (MN) frequency
      in exfoliated urothelial cells from voided urine from Colombian male non-smoking
      car painters and age-matched unexposed individuals. The exposed group had a
      higher percentage of individuals with >2 MNs/2000 cells compared with the
      unexposed group (P=0.04). Gene-specific analysis showed a significantly higher
      percentage of individuals with methylated GSTP1, p16(INK4a) and APC in the
      exposed group. Poisson regression analysis indicated that exposed individuals
      with methylated GSTP1 and p16(INK4a) promoters were more than twofold more likely
      to have an increase in MN frequency as compared with the reference. Finally,
      among exposed individuals with GSTP1 and p16(INK4a) methylated promoters, those
      with a greater age had a higher RR of increased MN frequency compared with
      younger exposed individuals with methylated promoters. These results support the
      conclusion that gene-specific promoter methylation may increase MN frequency in a
      dependent or independent interaction with occupational exposure to organic
      solvents. 

PMID- 25993026
TI  - Association of the Lipoprotein Receptor SCARB1 Common Missense Variant rs4238001
      with Incident Coronary Heart Disease.
AB  - BACKGROUND: Previous studies in mice and humans have implicated the lipoprotein
      receptor SCARB1 in association with atherosclerosis and lipid levels. In the
      current study, we sought to examine association of SCARB1 missense single
      nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease
      (CHD). METHODS AND RESULTS: Genotypes for rs4238001 were imputed for 2,319 White,
      1,570 African American, and 1,292 Hispanic-American MESA participants using the
      1,000 Genomes reference set. Cox proportional hazards models were used to
      determine association of rs4238001 with incident CHD, with adjustments for age,
      sex, study site, principal components of ancestry, body mass index, diabetes
      status, serum creatinine, lipid levels, hypertension status, education and
      smoking exposure. Meta-analysis across race/ethnic groups within MESA showed
      statistically significant association of the T allele with higher risk of CHD
      under a consistent and formally adjudicated definition of CHD events in this
      contemporary cohort study (hazard ratio [HR] = 1.49, 95% CI [1.04, 2.14], P =
      0.028). Analyses combining MESA with additional population-based cohorts expanded
      our samples in Whites (total n = 11,957 with 871 CHD events) and African
      Americans (total n = 5,962 with 355 CHD events) and confirmed an increased risk
      of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], P = 0.013), in African
      Americans (HR of 1.49 with 95% CI [1.07, 2.06], P = 0.019), in males (HR of 1.29
      with 95% CI [1.08, 1.54], P = 4.91 x 10(-3)) and in White males (HR of 1.24 with
      95% CI [1.03, 1.51], P = 0.026). CONCLUSION: SCARB1 missense rs4238001 is
      statistically significantly associated with incident CHD across a large
      population of multiple race/ethnic groups.

PMID- 25993027
TI  - Role of Prox1 in the Transforming Ascending Thin Limb of Henle's Loop during
      Mouse Kidney Development.
AB  - The homeobox transcription factor Prox1 is critical to the development of many
      embryonic organs and tissues, although current understanding of its expression in
      the developing renal medulla is limited. We examined the functional role of Prox1
      during mouse kidney development with particular emphasis on the developing loop
      of Henle. Our data show that Prox1 is expressed in the transdifferentiating
      region from the NKCC2-positive thick ascending limb, into the CLC-K1-positive
      ascending thin limb of Henle's loop beginning at embryonic day 18. From 1 to 14
      days of age, Prox1-positive cells gradually disappeared from the papillary tip,
      and remained in the initial part of inner medulla after 21 days. In this
      transforming area, no Prox1 was observed in cells undergoing apoptosis but was
      expressed strongly in the remaining cells, which differentiated into ascending
      thin limb epithelial cells. In vitro and in vivo approaches showed that Prox1
      expression increases where the osmolality is near optimal range, but decreases at
      below- or above-optimal ranges. Renal hypoosmolality induced by furosemide (NKCC2
      inhibitor) inhibited Prox1 expression and delayed maturation of the ascending
      limb of Henle's loop. Together, these studies suggest that Prox1 appears to be a
      critical stage specific regulator of specifying ascending thin limb cell fate and
      that its expression is regulated by osmolality. 

PMID- 25993028
TI  - Biofunctionalized prussian blue nanoparticles for multimodal molecular imaging
      applications.
AB  - Multimodal, molecular imaging allows the visualization of biological processes at
      cellular, subcellular, and molecular-level resolutions using multiple,
      complementary imaging techniques. These imaging agents facilitate the real-time
      assessment of pathways and mechanisms in vivo, which enhance both diagnostic and
      therapeutic efficacy. This article presents the protocol for the synthesis of
      biofunctionalized Prussian blue nanoparticles (PB NPs)--a novel class of agents
      for use in multimodal, molecular imaging applications. The imaging modalities
      incorporated in the nanoparticles, fluorescence imaging and magnetic resonance
      imaging (MRI), have complementary features. The PB NPs possess a core-shell
      design where gadolinium and manganese ions incorporated within the interstitial
      spaces of the PB lattice generate MRI contrast, both in T1 and T2-weighted
      sequences. The PB NPs are coated with fluorescent avidin using electrostatic self
      assembly, which enables fluorescence imaging. The avidin-coated nanoparticles are
      modified with biotinylated ligands that confer molecular targeting capabilities
      to the nanoparticles. The stability and toxicity of the nanoparticles are
      measured, as well as their MRI relaxivities. The multimodal, molecular imaging
      capabilities of these biofunctionalized PB NPs are then demonstrated by using
      them for fluorescence imaging and molecular MRI in vitro.

PMID- 25993029
TI  - Predicting classifier performance with limited training data: applications to
      computer-aided diagnosis in breast and prostate cancer.
AB  - Clinical trials increasingly employ medical imaging data in conjunction with
      supervised classifiers, where the latter require large amounts of training data
      to accurately model the system. Yet, a classifier selected at the start of the
      trial based on smaller and more accessible datasets may yield inaccurate and
      unstable classification performance. In this paper, we aim to address two common
      concerns in classifier selection for clinical trials: (1) predicting expected
      classifier performance for large datasets based on error rates calculated from
      smaller datasets and (2) the selection of appropriate classifiers based on
      expected performance for larger datasets. We present a framework for comparative
      evaluation of classifiers using only limited amounts of training data by using
      random repeated sampling (RRS) in conjunction with a cross-validation sampling
      strategy. Extrapolated error rates are subsequently validated via comparison with
      leave-one-out cross-validation performed on a larger dataset. The ability to
      predict error rates as dataset size increases is demonstrated on both synthetic
      data as well as three different computational imaging tasks: detecting cancerous
      image regions in prostate histopathology, differentiating high and low grade
      cancer in breast histopathology, and detecting cancerous metavoxels in prostate
      magnetic resonance spectroscopy. For each task, the relationships between 3
      distinct classifiers (k-nearest neighbor, naive Bayes, Support Vector Machine)
      are explored. Further quantitative evaluation in terms of interquartile range
      (IQR) suggests that our approach consistently yields error rates with lower
      variability (mean IQRs of 0.0070, 0.0127, and 0.0140) than a traditional RRS
      approach (mean IQRs of 0.0297, 0.0779, and 0.305) that does not employ cross
      validation sampling for all three datasets.

PMID- 25993030
TI  - Electroconvulsive Therapy as a Powerful Treatment for Delirium: A Case Report.
AB  - OBJECTIVE: The aim of the study was to describe the successful treatment of
      delirium with electroconvulsive therapy (ECT). METHODS: The method of the study
      was a case report. RESULTS: A 75-year-old man, with a recently diagnosed
      carcinoma of the parotid gland, was admitted with a fluctuating psychiatric
      syndrome. Delirium was diagnosed, although an acute underlying somatic cause
      could not be readily established. Antipsychotics and benzodiazepines were not
      effective. After 7 sessions of ECT, all symptoms ceased. This enabled him to
      receive radiotherapy for his tumor and enjoy a good quality of life for the
      remaining 8 months of his life. CONCLUSIONS: Electroconvulsive therapy is not
      only a powerful treatment for catatonia, neuroleptic malignant syndrome, and
      delirious mania but also for the most commonly occurring fluctuating psychiatric
      syndrome--delirium.

PMID- 25993031
TI  - The Role of the Psychiatric Mental Health: Advanced Practice Registered Nurse in
      the Scope of Psychiatric Practice.

PMID- 25993032
TI  - Clinical Challenges in Maintenance Electroconvulsive Therapy for Older Patients
      With Medical Comorbidity.
AB  - As patients receiving maintenance electroconvulsive therapy (MECT) age, many will
      acquire medical illnesses that may complicate their course of ECT and the
      treatment of their underlying psychiatric conditions. In this study, we present 7
      cases of patients receiving MECT whose medical illnesses resulted in clinical
      reassessment of whether or not MECT should be continued. We discuss clinical
      implications and considerations for treating medically ill patients with MECT. 

PMID- 25993033
TI  - A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury.
AB  - Four sphingolipid activator proteins (i.e., saposins A-D) are synthesized from a
      single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic
      effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good
      model in which to study neurotrophic factor elevation; PS and its mRNA are
      increased in neurons and the choroid plexus in this animal model. An 18-mer
      peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region
      prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule
      for use in alleviating ischemia-induced learning disabilities and neuronal loss.
      KA is a glutamate analog that stimulates excitatory neurotransmitter release and
      induces ischemia-like neuronal degeneration; it has been used to define
      mechanisms involved in neurodegeneration and neuroprotection. In the present
      study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18
      significantly improved behavioral deficits of Wistar rats (n = 6 per group), and
      enhanced the survival of hippocampal and cortical neurons against neurotoxicity
      induced by 12 mg/kg KA compared with control animals. PS18 significantly
      protected hippocampal synapses against KA-induced destruction. To evaluate the
      extent of PS18- and KA-induced effects in these hippocampal regions, we performed
      histological evaluations using semithin sections stained with toluidine blue, as
      well as ordinal sections stained with hematoxylin and eosin. We revealed a
      distinctive feature of KA-induced brain injury, which reportedly mimics ischemia,
      but affects a much wider area than ischemia-induced injury: KA induced neuronal
      degeneration not only in the CA1 region, where neurons degenerate following
      ischemia, but also in the CA2, CA3, and CA4 hippocampal regions. 

PMID- 25993035
TI  - Child With Abdominal Pain and a Cystic Pelvic Mass.

PMID- 25993034
TI  - Cost-effectiveness of collaborative care for the treatment of depressive
      disorders in primary care: a systematic review.
AB  - BACKGROUND: For the treatment of depressive disorders, the framework of
      collaborative care has been recommended, which showed improved outcomes in the
      primary care sector. Yet, an earlier literature review did not find sufficient
      evidence to draw robust conclusions on the cost-effectiveness of collaborative
      care. PURPOSE: To systematically review studies on the cost-effectiveness of
      collaborative care, compared with usual care for the treatment of patients with
      depressive disorders in primary care. METHODS: A systematic literature search in
      major databases was conducted. Risk of bias was assessed using the Cochrane
      Collaboration's tool. Methodological quality of the articles was assessed using
      the Consensus on Health Economic Criteria (CHEC) list. To ensure comparability
      across studies, cost data were inflated to the year 2012 using country-specific
      gross domestic product inflation rates, and were adjusted to international
      dollars using purchasing power parities (PPP). RESULTS: In total, 19 cost
      effectiveness analyses were reviewed. The included studies had sample sizes
      between n = 65 to n = 1,801, and time horizons between six to 24 months. Between
      42% and 89% of the CHEC quality criteria were fulfilled, and in only one study no
      risk of bias was identified. A societal perspective was used by five studies.
      Incremental costs per depression-free day ranged from dominance to US$PPP 64.89,
      and incremental costs per QALY from dominance to US$PPP 874,562. CONCLUSION:
      Despite our review improved the comparability of study results, cost
      effectiveness of collaborative care compared with usual care for the treatment of
      patients with depressive disorders in primary care is ambiguous depending on
      willingness to pay. A still considerable uncertainty, due to inconsistent
      methodological quality and results among included studies, suggests further cost
      effectiveness analyses using QALYs as effect measures and a time horizon of at
      least 1 year.

PMID- 25993036
TI  - Acquired Drug Resistance in Mycobacterium tuberculosis and Poor Outcomes among
      Patients with Multidrug-Resistant Tuberculosis.
AB  - Rates and risk factors for acquired drug resistance and association with outcomes
      among patients with multidrug-resistant tuberculosis (MDR TB) are not well
      defined. In an MDR TB cohort from the country of Georgia, drug susceptibility
      testing for second-line drugs (SLDs) was performed at baseline and every third
      month. Acquired resistance was defined as any SLD whose status changed from
      susceptible at baseline to resistant at follow-up. Among 141 patients, acquired
      resistance in Mycobacterium tuberculosis was observed in 19 (14%); prevalence was
      9.1% for ofloxacin and 9.8% for capreomycin or kanamycin. Baseline cavitary
      disease and resistance to >6 drugs were associated with acquired resistance.
      Patients with M. tuberculosis that had acquired resistance were at significantly
      increased risk for poor treatment outcome compared with patients without these
      isolates (89% vs. 36%; p<0.01). Acquired resistance occurs commonly among
      patients with MDR TB and impedes successful treatment outcomes. 

PMID- 25993037
TI  - High accuracy thermal conductivity measurement of aqueous cryoprotective agents
      and semi-rigid biological tissues using a microfabricated thermal sensor.
AB  - An improved thermal-needle approach for accurate and fast measurement of thermal
      conductivity of aqueous and soft biomaterials was developed using microfabricated
      thermal conductivity sensors. This microscopic measuring device was
      comprehensively characterized at temperatures from 0  degrees C to 40  degrees C.
      Despite the previous belief, system calibration constant was observed to be
      highly temperature-dependent. Dynamic thermal conductivity response during
      cooling (40  degrees C to -40  degrees C) was observed using the miniaturized
      single tip sensor for various concentrations of CPAs, i.e., glycerol, ethylene
      glycol and dimethyl sulfoxide. Chicken breast, chicken skin, porcine limb, and
      bovine liver were assayed to investigate the effect of anatomical heterogeneity
      on thermal conductivity using the arrayed multi-tip sensor at 20  degrees C.
      Experimental results revealed distinctive differences in localized thermal
      conductivity, which suggests the use of approximated or constant property values
      is expected to bring about results with largely inflated uncertainties when
      investigating bio-heat transfer mechanisms and/or performing sophisticated
      thermal modeling with complex biological tissues. Overall, the presented micro
      thermal sensor with automated data analysis algorithm is a promising approach for
      direct thermal conductivity measurement of aqueous solutions and soft
      biomaterials and is of great value to cryopreservation of tissues, hyperthermia
      or cryogenic, and other thermal-based clinical diagnostics and treatments.

PMID- 25993038
TI  - Effectiveness of social behaviors for autonomous wheelchair robot to support
      elderly people in Japan.
AB  - We developed a wheelchair robot to support the movement of elderly people and
      specifically implemented two functions to enhance their intention to use it:
      speaking behavior to convey place/location related information and speed
      adjustment based on individual preferences. Our study examines how the
      evaluations of our wheelchair robot differ when compared with human caregivers
      and a conventional autonomous wheelchair without the two proposed functions in a
      moving support context. 28 senior citizens participated in the experiment to
      evaluate three different conditions. Our measurements consisted of questionnaire
      items and the coding of free-style interview results. Our experimental results
      revealed that elderly people evaluated our wheelchair robot higher than the
      wheelchair without the two functions and the human caregivers for some items. 

PMID- 25993040
TI  - Awareness and Attitude towards Breastfeeding among Two Generations of Indian
      Women: A Comparative Study.
AB  - INTRODUCTION: Present study was aimed to analyze the impact of education,
      employment and financial independence in breastfeeding practices among Indian
      women. METHODOLOGY: Present explorative questionnaire based survey included 256
      women (128 pairs) in the final analysis. A pair means--a) pregnant lady (in her
      third trimester) representing younger generation and b) her mother/mother in law
      representing the elder generation. RESULTS: We found that the overall awareness
      regarding 'breast milk' being the best food for baby was excellent (overall
      97.3%; younger generation: 96.9%; elder generation: 97.7%). Overall knowledge
      regarding the correct technique (28.9% younger generation and 21.9% elder
      generation) and frequency of breastfeeding (20.3% of younger generation and 34.4%
      of elder generation) was very poor. Less than 60% (younger generation: 57.8%;
      elder generation: 58.6%) were aware that the only major contraindication for
      breastfeeding is a mother infected with human immunodeficiency virus (HIV). On
      comparing responses obtained from the two generations of women, difference was
      not statistically significant among most of the issues related to breastfeeding.
      With regards to the attitude, despite better awareness, only 94.5% women in
      younger generation and 89.1% women in elder generation were planning to give
      mother's milk as the first feed to the newborn. Similarly, less than 75% of women
      were ready to breast-feed the newborn immediately after birth. This was
      contradictory to the fact that 86% of pregnant women were aware that the baby
      should be breast-fed within an hour of birth. CONCLUSION: Awareness with regards
      to breastfeeding issues had not changed significantly with the educational
      progress of Indian women. Despite the good level of awareness in the society
      regarding breastfeeding, attitude to practice the same is lacking.

PMID- 25993039
TI  - The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus
      Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma
      Cells.
AB  - BACKGROUND: A phase I/II trial for glioblastoma with the oncolytic adenovirus
      Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells
      with a disrupted retinoblastoma-pathway and enters cells via alphavbeta3/5
      integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC
      inhibitors (HDACi) affect integrins and share common cell death pathways with
      Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24
      RGD in patient-derived glioblastoma stem-like cells (GSC), and we determined the
      most effective HDACi. METHODS: SAHA, Valproic Acid, Scriptaid, MS275 and LBH589
      were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined
      by Chou Talalay method. Viral infection and replication were assessed using
      luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie
      adenovirus receptor and alphavbeta3 integrin levels were determined by flow
      cytometry. Oncolysis and mechanisms of cell death were studied by viability,
      caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal
      human astrocytes. MGMT promotor methylation status, TCGA classification, Rb
      pathway and integrin gene expression levels were assessed as markers of
      responsiveness. RESULTS: Scriptaid and LBH589 acted synergistically with Delta24
      RGD in approximately 50% of the GSCs. Both drugs moderately increased alphavbeta3
      integrin levels and viral infection in responding but not in non-responding GSCs.
      LBH589 moderately increased late viral gene expression, however, virus titration
      revealed diminished viral progeny production by both HDACi, Scriptaid augmented
      caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as
      well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption.
      Responsiveness correlated with expression of various Rb-pathway genes and
      integrins. Combination treatments induced limited toxicity to human astrocytes.
      CONCLUSION: LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic
      anti-tumor activity in a subset of GSCs. Both HDACi moderately augmented viral
      infection and late gene expression, but slightly reduced progeny production. The
      drugs differentially activated multiple cell death pathways. The limited toxicity
      on astrocytes supports further evaluation of the proposed combination therapies.

PMID- 25993041
TI  - Enhanced Radio Frequency Biosensor for Food Quality Detection Using
      Functionalized Carbon Nanofillers.
AB  - This paper outlines an improved design of inexpensive, wireless and battery free
      biosensors for in situ monitoring of food quality. This type of device has an
      additional advantage of being operated remotely. To make the device, a portion of
      an antenna of a passive 13.56 MHz radio frequency identification (RFID) tag was
      altered with a sensing element composed of conductive nanofillers/particles, a
      binding agent, and a polymer matrix. These novel RFID tags were exposed to
      biogenic amine putrescine, commonly used as a marker for food spoilage, and their
      response was monitored over time using a general-purpose network analyzer. The
      effect of conductive filler properties, including conductivity and morphology,
      and filler functionalization was investigated by preparing sensing composites
      containing carbon particles (CPs), multiwall carbon nanotubes (MWCNTs), and
      binding agent grafted-multiwall carbon nanotubes (g-MWCNTs), respectively. During
      exposure to putrescine, the amount of reflected waves, frequency at resonance,
      and quality factor of the novel RFID tags decreased in response. The use of
      MWCNTs reduced tag cutoff time (i.e., faster response time) as compared with the
      use of CPs, which highlighted the effectiveness of the conductive nanofiller
      morphology, while the addition of g-MWCNTs further accelerated the sensor
      response time as a result of localized binding on the conductive nanofiller
      surface. Microstructural investigation of the film morphology indicated a better
      dispersion of g-MWCNTs in the sensing composite as compared to MWCNTs and CPs, as
      well as a smoother texture of the surface of the resulting coating. These results
      demonstrated that grafting of the binding agent onto the conductive particles in
      the sensing composite is an effective way to further enhance the detection
      sensitivity of the RFID tag based sensor. 

PMID- 25993043
TI  - Model of Water Sorption and Swelling in Polymer Electrolyte Membranes: Diagnostic
      Applications.
AB  - This work expands on the poroelectroelastic model of water sorption in polymer
      electrolyte membranes. It links membrane water sorption and the evolution of the
      pore size distribution with the microscopic charge density distribution at pore
      surfaces and the microscopic shear modulus of polymeric pore walls. We evaluate
      different deformation modes of polymeric pore walls to derive stress-strain
      relationships that determine the law of swelling. Thereafter, the model is
      applied to different sets of water sorption data for membranes that were
      submitted to either hygrothermal aging or chemical degradation. The model-based
      analysis relates the macroscopic state of swelling to the evolution of the
      statistical distribution of the pore radius as well as of the microscopic fluid
      and elastic pressures. Changes in the surface charge density at pore surfaces and
      elastic pressure of pore walls, induced by degradation, can be rationalized.
      These insights are useful in view of understanding degradation mechanisms and
      their structural effects. 

PMID- 25993042
TI  - Integrative genomic signatures of hepatocellular carcinoma derived from
      nonalcoholic Fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a risk factor for Hepatocellular
      carcinoma (HCC), but he transition from NAFLD to HCC is poorly understood.
      Feature selection algorithms in human and genetically modified mice NAFLD and HCC
      microarray data were applied to generate signatures of NAFLD progression and HCC
      differential survival. These signatures were used to study the pathogenesis of
      NAFLD derived HCC and explore which subtypes of cancers that can be investigated
      using mouse models. Our findings show that: (I) HNF4 is a common potential
      transcription factor mediating the transcription of NAFLD progression genes (II)
      mice HCC derived from NAFLD co-cluster with a less aggressive human HCC subtype
      of differential prognosis and mixed etiology (III) the HCC survival signature is
      able to correctly classify 95% of the samples and gives Fgf20 and Tgfb1i1 as the
      most robust genes for prediction (IV) the expression values of genes composing
      the signature in an independent human HCC dataset revealed different HCC subtypes
      showing differences in survival time by a Logrank test. In summary, we present
      marker signatures for NAFLD derived HCC molecular pathogenesis both at the gene
      and pathway level. 

PMID- 25993044
TI  - Novel rare-earth-free yellow Ca5Zn3.92In0.08(V0.99Ta0.01O4)6 phosphors for
      dazzling white light-emitting diodes.
AB  - White light-emitting diode (WLED) products currently available on the market are
      based on the blue LED combined with yellow phosphor approach. However, these
      WLEDs are still insufficient for general illumination and flat panel display
      (FPD) applications because of their low color-rendering index (CRI < 75) and high
      correlated color temperature (CCT = 6000 K). Although near-ultraviolet (UV) LED
      chips provide more efficient excitation than blue chips, YAG:Ce(3+) phosphors
      have very weak excitation in the near-UV spectral region. Hence, there is an
      increasing demand for novel yellow phosphor materials with excitation in the near
      UV region. In this work, we report novel self-activated yellow
      Ca(5)Zn(3.92)In(0.08)(V(0.99)Ta(0.01)O(4))(6) (CZIVT) phosphors that efficiently
      convert near-UV excitation light into yellow luminescence. The crystal structure
      and lattice parameters of these CZIVT phosphors are elucidated through Rietveld
      refinement. Through doping with In(3+) and Ta(5+) ions, the emission intensity is
      enhanced in the red region, and the Stokes shift is controlled to obtain good
      color rendition. When a near-UV LED chip is coated with a combination of CZIVT
      and commercial blue Ba(0.9)Eu(0.1)MgAl(10)O(17) phosphors, a pleasant WLED with a
      high CRI of 82.51 and a low CCT of 5231 K, which are essential for indoor
      illumination and FPDs, is achieved.

PMID- 25993045
TI  - Assessment of the quality of the childhood physical abuse measure in the National
      Population Health Survey.
AB  - BACKGROUND: The long-term health consequences of childhood physical abuse are
      often studied using retrospective self-reports collected from adults. This study
      assesses the quality of a question on childhood physical abuse in the National
      Population Health Survey (NPHS). DATA AND METHODS: All NPHS respondents aged 18
      or older (n = 15,027) were asked a question about childhood physical abuse in
      cycles 1 (1994/1995), 7 (2006/2007) and 8 (2008/2009). The reliability of this
      question was assessed over these periods. Associations between response patterns
      to the abuse item and health conditions that are related to childhood physical
      abuse were examined. RESULTS: Across all NPHS cycles, very few respondents
      refused to answer or replied "don't know" to the item on childhood physical
      abuse. Reliability, as measured by Cohen's kappa statistic, was "substantial" for
      the two-year interval between cycles 7 and 8, and "moderate" for the 12- and 14
      year intervals from cycle 1. Kappa estimates were similar when examined by
      various demographic factors. Compared with consistent deniers, respondents who
      consistently affirmed childhood physical abuse and those who provided
      inconsistent responses had increased odds of depression, fair or poor self
      perceived health, disability, migraine, and heart disease. INTERPRETATION:
      Despite some limitations, the NPHS question on childhood physical abuse allows
      researchers to investigate long-term health consequences of abuse.

PMID- 25993046
TI  - Performance of the cancer risk management model lung cancer screening module.
AB  - BACKGROUND: The National Lung Screening Trial (NLST) demonstrated that low-dose
      computed tomography (LDCT) screening reduces lung cancer mortality in a high-risk
      U.S. population. A microsimulation model of LDCT screening was developed to
      estimate the impact of introducing population-based screening in Canada. DATA AND
      METHODS: LDCT screening was simulated using the lung cancer module of the Cancer
      Risk Management Model (CRMM-LC), which generates large, representative samples of
      the Canadian population from which a cohort with characteristics similar to NLST
      participants was selected. Screening parameters were estimated for stage shift,
      LDCT sensitivity and specificity, lead time, and survival to fit to NLST
      incidence and mortality results. The estimation process was a step-wise directed
      search. RESULTS: Simulated mortality reduction from LDCT screening was 23% in the
      CRMM-LC, compared with 20% in the NLST. The difference in the number of lung
      cancer cases over six years varied by, at most, 2.3% in the screen arm. The
      difference in cumulative incidence at six years was less than 2% in both screen
      and control arms. The estimated percentage over-diagnosed was 24.8%, which was 6%
      higher than NLST results. INTERPRETATION: Simulated screening reproduces NLST
      results. The CRMM-LC can evaluate a variety of population-based screening
      strategies. Sensitivity analyses are recommended to provide a range of
      projections to reflect model uncertainty.

PMID- 25993047
TI  - Clinical trial of prophylactic extended-field carbon-ion radiotherapy for locally
      advanced uterine cervical cancer (protocol 0508).
AB  - To evaluate the efficacy and the toxicity of prophylactic extended-field carbon
      ion radiotherapy (C-ion RT, Protocol 0508) for locally advanced squamous cell
      carcinoma of the uterine cervix in phase I / II clinical trial. Between May 2006
      and January 2012, 26 patients of Protocol 0508 were treated with C-ion RT. The
      numbers of patients with stage IIB, IIIB, and IVA disease were 13, 11, and 2,
      respectively. Twenty patients had pelvic lymph node metastases. Median tumor size
      was 6.1 cm (range, 4.0-10.0 cm). The treatment consisted of extended-field
      irradiation of 39.0 gray equivalents (GyE) in 13 fractions, and additional 15.0
      GyE in 5 fractions was given to the gross tumor volume (GTV) and surrounding
      tissues. With regard to local boost, 18.0 GyE in 2 fractions was given to GTV
      only. Total dose to the cervical tumor was 72.0 GyE over 20 fractions. The median
      follow-up period was 37 months. Twenty-one patients had grade 1 or 2 acute
      gastrointestinal toxicity, but all patients completed the treatment on schedule.
      There were no grade 3 or higher late complications, with 8 patients having grade
      1 or 2 toxicities, 1 had grade 2 gastrointestinal toxicity and 2 had grade 2
      genitourinary toxicity. Four patients (15.4%) developed local recurrence, and 8
      patients (30.8%) had distant metastases. The 2-year local control rate,
      progression-free survival rate and overall survival rate were 83.6%, 61.5% and
      73.1%, respectively. There were no severe acute or late complications in this
      trial. Prophylactic extended-field C-ion RT for locally advanced squamous cell
      carcinoma of the uterine cervix was a safe treatment. Although the number of
      patients in this study was small, the results support further investigations to
      confirm the therapeutic efficacy and to avoid or reduce toxicity. TRIAL
      REGISTRATION: UMIN-CTR UMIN000016169.

PMID- 25993048
TI  - Self-assembly of complex two-dimensional shapes from single-stranded DNA tiles.
AB  - Current methods in DNA nano-architecture have successfully engineered a variety
      of 2D and 3D structures using principles of self-assembly. In this article, we
      describe detailed protocols on how to fabricate sophisticated 2D shapes through
      the self-assembly of uniquely addressable single-stranded DNA tiles which act as
      molecular pixels on a molecular canvas. Each single-stranded tile (SST) is a 42
      nucleotide DNA strand composed of four concatenated modular domains which bind to
      four neighbors during self-assembly. The molecular canvas is a rectangle
      structure self-assembled from SSTs. A prescribed complex 2D shape is formed by
      selecting the constituent molecular pixels (SSTs) from a 310-pixel molecular
      canvas and then subjecting the corresponding strands to one-pot annealing. Due to
      the modular nature of the SST approach we demonstrate the scalability,
      versatility and robustness of this method. Compared with alternative methods, the
      SST method enables a wider selection of information polymers and sequences
      through the use of de novo designed and synthesized short DNA strands. 

PMID- 25993049
TI  - Diffuse reflectance infrared spectroscopic identification of dispersant/particle
      bonding mechanisms in functional inks.
AB  - In additive manufacturing, or 3D printing, material is deposited drop by drop, to
      create micron to macroscale layers. A typical inkjet ink is a colloidal
      dispersion containing approximately ten components including solvent, the nano to
      micron scale particles which will comprise the printed layer, polymeric
      dispersants to stabilize the particles, and polymers to tune layer strength,
      surface tension and viscosity. To rationally and efficiently formulate such an
      ink, it is crucial to know how the components interact. Specifically, which
      polymers bond to the particle surfaces and how are they attached? Answering this
      question requires an experimental procedure that discriminates between polymer
      adsorbed on the particles and free polymer. Further, the method must provide
      details about how the functional groups of the polymer interact with the
      particle. In this protocol, we show how to employ centrifugation to separate
      particles with adsorbed polymer from the rest of the ink, prepare the separated
      samples for spectroscopic measurement, and use Diffuse Reflectance Fourier
      Transform Infrared Spectroscopy (DRIFTS) for accurate determination of
      dispersant/particle bonding mechanisms. A significant advantage of this
      methodology is that it provides high level mechanistic detail using only simple,
      commonly available laboratory equipment. This makes crucial data available to
      almost any formulation laboratory. The method is most useful for inks composed of
      metal, ceramic, and metal oxide particles in the range of 100 nm or greater.
      Because of the density and particle size of these inks, they are readily
      separable with centrifugation. Further, the spectroscopic signatures of such
      particles are easy to distinguish from absorbed polymer. The primary limitation
      of this technique is that the spectroscopy is performed ex-situ on the separated
      and dried particles as opposed to the particles in dispersion. However, results
      from attenuated total reflectance spectra of the wet separated particles provide
      evidence for the validity of the DRIFTS measurement. 

PMID- 25993050
TI  - Nurses' attitudes and beliefs to attempted suicide in Southern India.
AB  - BACKGROUND: There is growing global interest into the attitudes and clinical
      management of persons who have attempted suicide. AIMS: The principal purpose was
      to determine senior nursing staff attitudes towards patients who had attempted
      suicide from a professional and cultural perspective, which might influence care
      following hospital admission. The focus concerned nursing staff interactions at a
      psychological level that compete with physical tasks on general hospital wards.
      METHODS: A qualitative methodology was employed with audio-taped interviews
      utilising four level data coding. This article reports on a group of 15 nursing
      staff from a large general hospital in Mysore, Southern India. RESULTS: Findings
      suggested that patient care and treatment is directly influenced by the nurse's
      religious beliefs within a general hospital setting with physical duties
      prioritised over psychological support, which was underdeveloped throughout the
      participant group. CONCLUSION: The results allow a series of recommendations for
      educational and skills initiatives before progressing to patient assessment and
      treatment projects and cross-cultural comparison studies. In addition,
      interventions must focus on current resources and context to move the evidence
      based suicide prevention forward.

PMID- 25993051
TI  - Factors Associated With Occupational Sun-Protection Policies in Local Government
      Organizations in Colorado.
AB  - IMPORTANCE: Skin cancer prevention remains a national priority. Reducing chronic
      UV radiation exposure for outdoor workers through sun-safety practices is an
      important step to help reduce the incidence of skin cancer. OBJECTIVE: To
      determine the presence of occupational sun-safety policies at local government
      organizations in a single state. DESIGN, SETTING, AND PARTICIPANTS: Of 571
      potentially eligible local government organizations of Colorado cities, counties,
      and special tax districts, we enrolled 98 in a randomized pretest-posttest
      controlled experiment starting August 15, 2010, that evaluated an intervention to
      promote the adoption of sun-safety policies. We used a policy-coding protocol to
      evaluate personal sun-protection practices, environmental and administrative
      controls, and policy directives for sun safety starting February 10, 2011. We
      report the baseline assessment of the occupational sun-protection policies of
      these organizations. MAIN OUTCOMES AND MEASURES: The presence of an occupational
      sun-safety policy. RESULTS: Overall, 85 local government organizations (87%) had
      policies that required personal sun-protection practices, including the use of
      eyewear, hats, and protective clothing. However, of the 98 responding
      organizations, only 8 hat policies (8%), 10 eyewear policies (10%), and 7
      clothing policies (7%) mentioned sun protection as the intent of the policy. Only
      cosmopoliteness, operationalized as proximity to an urban area, was associated
      with the presence of a sun-safety policy (odds ratio, 0.99 [95% CI, 0.98-1.00]; P
      = .02). CONCLUSIONS AND RELEVANCE: Outdoor workers are at increased risk for skin
      cancer because of long-term exposure to solar UV radiation. Although
      organizational policies have the potential to increase sun protection in
      occupational settings, occupational sun-safety policies were uncommon among local
      governments. Opportunities exist for dermatologists and other physicians to
      influence occupational sun-safety practices and policies, which are consistent
      with other safety procedures and could easily be integrated into existing
      workplace practices.

PMID- 25993053
TI  - Components and public health impact of population growth in the Arab world.
AB  - The Arab world, which consists of the 22 member states of the Arab League, is
      undergoing a rapid transition in demographics, including fertility, mortality,
      and migration. Comprising a distinctive geographic region spread across West Asia
      and North East Africa and unified by the Arabic language, these states share
      common values and characteristics despite having diverse economic and political
      conditions. The demographic lag (high fertility and low mortality) that
      characterizes the Arab world is unique, but the present trend of declining
      fertility, combined with the relatively low mortality, brings about significant
      changes in its population size. This research aimed to: (i) assess the population
      growth in the Arab world over 3 time periods, (ii) explore its components, and
      (iii) understand its public health impact. Data from the International Data Base
      (IDB) of the U.S. Census Bureau for 3 time periods (1992, 2002, and 2012) in 21
      countries of the Arab world were analyzed by dividing them into four geographic
      sectors, namely, the Gulf Cooperation Council (GCC), West Asia, Maghreb, and the
      Nile Valley African Horn. The population of the Arab world has grown considerably
      due to both natural growth and migration. The immigration is pronounced,
      especially into resource-intensive GCC nations, not only from East Asian and
      Central African countries but also from resource-thrifty (limited-resource) Arab
      nations. The migrations within, as well as outside, the Arab world reveal an
      interesting demographic phenomenon that requires further research: migration
      flows and trends. However, the transformations in public health statistics
      related to mortality-the impact of demographic changes-depict a new era in the
      Arab world. 

PMID- 25993052
TI  - Impact of Chronic Periodontitis on Levels of Glucoregulatory Biomarkers in
      Gingival Crevicular Fluid of Adults with and without Type 2 Diabetes.
AB  - The relationship between diabetes and periodontal disease is bidirectional, but
      information about the effect of chronic periodontitis on the levels of the
      glucoregulatory biomarkers locally in gingival crevicular fluid (GCF) is limited.
      The aim of this study was to compare the levels of 10 glucoregulatory biomarkers
      in GCF, firstly in subjects with type 2 diabetes (T2DM) presenting with and
      without chronic periodontitis and secondly, in subjects without diabetes, with
      and without chronic periodontitis. The material comprised a total of 152
      subjects, stratified as: 54 with T2DM and chronic periodontitis (G1), 24 with
      T2DM (G2), 30 with chronic periodontitis (G3) and 44 without T2DM or
      periodontitis (G4). The levels of the biomarkers were measured using multiplex
      biometric immunoassays. Periodontal pocket depths were recorded in mm. Subsets G1
      and G2 and subsets G3 and G4 were compared independently. Among T2DM subjects,
      GIP, GLP-1 and glucagon were significantly up-regulated in G1 compared to G2.
      Moreover, there were no statistical differences between the two groups regarding
      C-peptide, insulin, ghrelin, leptin and PAI-1. Comparisons among individuals
      without T2DM revealed significantly lower amounts of C-peptide and ghrelin in G3
      than in G4. The number of sites with pocket depth >= 4mm correlated negatively
      with C-peptide (Spearman's correlation co-efficient: -0.240, P < 0.01) and
      positively with GIP and visfatin (Spearman's correlation co-efficient: 0.255 and
      0.241, respectively, P < 0.01). The results demonstrate that chronic
      periodontitis adversely influences the GCF levels of glucoregulatory biomarkers,
      as it is associated with disturbed levels of biomarkers related to the onset of
      T2DM and its medical complications. 

PMID- 25993054
TI  - Comparing and Using Occupation-Focused Models.
AB  - As health care moves toward understanding the importance of function,
      participation and occupation, occupational therapists would be well served to use
      occupation-focused theories to guide intervention. Most therapists understand
      that applying occupation-focused models supports best practice, but many do not
      routinely use these models. Barriers to application of theory include lack of
      understanding of the models and limited strategies to select and apply them for
      maximum client benefit. The aim of this article is to compare occupation-focused
      models and provide recommendations on how to choose and combine these models in
      practice; and to provide a systematic approach for integrating occupation-focused
      models with frames of reference to guide assessment and intervention. 

PMID- 25993055
TI  - Influence of sociodemographic characteristics on human mobility [corrected].
AB  - Human mobility has been traditionally studied using surveys that deliver
      snapshots of population displacement patterns. The growing accessibility to ICT
      information from portable digital media has recently opened the possibility of
      exploring human behavior at high spatio-temporal resolutions. Mobile phone
      records, geolocated tweets, check-ins from Foursquare or geotagged photos, have
      contributed to this purpose at different scales, from cities to countries, in
      different world areas. Many previous works lacked, however, details on the
      individuals' attributes such as age or gender. In this work, we analyze credit
      card records from Barcelona and Madrid and by examining the geolocated credit
      card transactions of individuals living in the two provinces, we find that the
      mobility patterns vary according to gender, age and occupation. Differences in
      distance traveled and travel purpose are observed between younger and older
      people, but, curiously, either between males and females of similar age. While
      mobility displays some generic features, here we show that sociodemographic
      characteristics play a relevant role and must be taken into account for mobility
      and epidemiological modelization. 

PMID- 25993056
TI  - Fine Mapping and Characterization of Candidate Genes that Control Resistance to
      Cercospora sojina K. Hara in Two Soybean Germplasm Accessions.
AB  - Frogeye leaf spot (FLS), caused by the fungus Cercospora sojina K. Hara, may
      cause a significant yield loss to soybean growers in regions with a warm and
      humid climate. Two soybean accessions, PI 594891 and PI 594774, were identified
      to carry a high level of resistance similar to that conditioned by the Rcs3 gene
      in 'Davis'. Previously, we reported that the resistance to FLS in these two plant
      introductions (PIs) was controlled by a novel gene (s) on chromosome 13 that is
      different from Rcs3. To fine-map the novel FLS resistance gene(s) in these two
      PIs, F2: 3 seeds from the crosses between PI 594891 and PI 594774, and the FLS
      susceptible genotype 'Blackhawk' were genotyped with SNP markers that were
      designed based on the SoySNP50k iSelect BeadChip data to identify recombinant
      events and locate candidate genes. Analysis of lines possessing key recombination
      events helped narrow down the FLS-resistance genomic region in PI 594891 from 3.3
      Mb to a 72.6 kb region with five annotated genes. The resistance gene in PI
      594774 was fine-mapped into a 540 kb region that encompasses the 72.6 kb region
      found in PI 594891. Sequencing five candidate genes in PI 594891 identified three
      genes that have several mutations in the promoter, intron, 5', and 3' UTR
      regions. qPCR analysis showed a difference in expression levels of these genes in
      both lines compared to Blackhawk in the presence of C. sojina. Based on
      phenotype, genotype and haplotype analysis results, these two soybean accessions
      might carry different resistance alleles of the same gene or two different
      gene(s). The identified SNPs were used to develop Kompetitive Allele Specific PCR
      (KASP) assays to detect the resistance alleles on chromosome 13 from the two PIs
      for marker-assisted selection. 

PMID- 25993057
TI  - Utilizing the antigen capsid-incorporation strategy for the development of
      adenovirus serotype 5-vectored vaccine approaches.
AB  - Adenovirus serotype 5 (Ad5) has been extensively modified with traditional
      transgene methods for the vaccine development. The reduced efficacies of these
      traditionally modified Ad5 vectors in clinical trials could be primarily
      correlated with Ad5 pre-existing immunity (PEI) among the majority of the
      population. To promote Ad5-vectored vaccine development by solving the concern of
      Ad5 PEI, the innovative Antigen Capsid-Incorporation strategy has been employed.
      By merit of this strategy, Ad5-vectored we first constructed the hexon shuttle
      plasmid HVR1-KWAS-HVR5-His6/pH5S by subcloning the hypervariable region (HVR) 1
      of hexon into a previously constructed shuttle plasmid HVR5-His6/pH5S, which had
      His6 tag incorporated into the HVR5. This HVR1 DNA fragment containing a HIV
      epitope ELDKWAS was synthesized. HVR1-KWAS-HVR5-His6/pH5S was then linearized and
      co-transformed with linearized backbone plasmid pAd5/?H5 (GL) , for homologous
      recombination. This recombined plasmid pAd5/H5-HVR1-KWAS-HVR5-His6 was
      transfected into cells to generate the viral vector Ad5/H5-HVR1-KWAS-HVR5-His6.
      This vector was validated to have qualitative fitness indicated by viral physical
      titer (VP/ml), infectious titer (IP/ml) and corresponding VP/IP ratio. Both the
      HIV epitope and His6 tag were surface-exposed on the Ad5 capsid, and retained
      epitope-specific antigenicity of their own. A neutralization assay indicated the
      ability of this divalent vector to circumvent neutralization by Ad5-positive sera
      in vitro. Mice immunization demonstrated the generation of robust humoral
      immunity specific to the HIV epitope and His6. This proof-of-principle study
      suggested that the protocol associated with the Antigen Capsid-Incorporation
      strategy could be feasibly utilized for the generation of Ad5-vectored vaccines
      by modifying different capsid proteins. This protocol could even be further
      modified for the generation of rare-serotype adenovirus-vectored vaccines. 

PMID- 25993059
TI  - Structure-Activity Relationship Studies of a Series of Semisynthetic Lipopeptides
      Leading to the Discovery of Surotomycin, a Novel Cyclic Lipopeptide Being
      Developed for the Treatment of Clostridium difficile-Associated Diarrhea.
AB  - Novel cyclic lipopeptides with different acyl tails were synthesized via a
      semisynthetic approach. Structure-activity relationship studies revealed that
      lipophilicity, chain length, and the location of key aromatic functionalities of
      the tail modulated activity. The lead compound surotomycin exhibited
      significantly improved in vitro activity compared with daptomycin (MIC90 0.5 vs 2
      MUg/mL) against Clostridium difficile including NAP1 epidemic strains. In hamster
      efficacy studies, surotomycin protected animals at a dose of 0.5 mg/kg, PO. 

PMID- 25993058
TI  - Pathogenic nontuberculous mycobacteria resist and inactivate cathelicidin:
      implication of a novel role for polar mycobacterial lipids.
AB  - Nontuberculous mycobacteria (NTM) are a large group of environmental organisms
      with worldwide distribution, but only a relatively few are known to be
      pathogenic. Chronic, debilitating lung disease is the most common manifestation
      of NTM infection, which is often refractory to treatment. The incidence and
      prevalence of NTM lung disease are increasing in the United States and in many
      parts of the world. Hence, a more complete understanding of NTM pathogenesis will
      provide the foundation to develop innovative approaches to treat this
      recalcitrant disease. Herein, we demonstrate that several species of NTM show
      broad resistance to the antimicrobial peptide, cathelicidin (LL-37). Resistance
      to LL-37 was not significantly different between M. avium that contain serovar
      specific glycopeptidolipid (GPL, M. aviumssGPL) and M. avium that do not (M.
      aviumDeltassGPL). Similarly, M. abscessus containing non-specific GPL (M.
      abscessusnsGPL(+)) or lacking nsGPL (M. abscessusnsGPL(-)) remained equally
      resistant to LL-37. These findings would support the notion that GPL are not the
      components responsible for NTM resistance to LL-37. Unexpectedly, the growth of
      M. abscessusnsGPL(-) increased with LL-37 or scrambled LL-37 peptide in a dose
      dependent fashion. We also discovered that LL-37 exposed to NTM had reduced
      antimicrobial activity, and initial work indicates that this is likely due to
      inactivation of LL-37 by lipid component(s) of the NTM cell envelope. We conclude
      that pathogenic NTM resist and inactivate LL-37. The mechanism by which NTM
      circumvent the antimicrobial activity of LL-37 remains to be determined. 

PMID- 25993061
TI  - Evolution of exhaled nitric oxide levels throughout development and aging of
      healthy humans.
AB  - It is not fully understood how the fraction of exhaled nitric oxide (FeNO) varies
      with age and gender in healthy individuals. We aim to describe the evolution of
      FeNO with age, giving special regard to the effect of gender, and to relate this
      evolution to natural changes in the respiratory tract.We studied 3081 subjects
      from NHANES 2007-08 and 2009-10, aged 6-80 years, with no self-reported diagnosis
      of asthma, chronic bronchitis or emphysema, and with normal values of blood
      eosinophils and C-reactive protein. The relationship of the mean values of FeNO
      to age, in all participants and divided by gender, was computed, and compared
      with changes in anatomic dead space volume and forced vital capacity. A change
      point analysis technique and subsequent piecewise regression was used to detect
      breakpoints in the evolution of FeNO with age.Three distinct phases in the
      evolution of FeNO throughout the age range 6-80 years can be seen. FeNO values
      increase linearly between 6-14 years of age in girls and between 6-16 years of
      age in boys, in parallel with somatic growth. After that, FeNO levels plateau in
      both genders until age 45 years in females and age 59 years in males, when they
      start to increase linearly again. This increase continues until age 80.Our data
      clearly show a triphasic evolution of FeNO throughout the human age range in
      healthy individuals. This should be accounted for in development of reference
      equations for normal FeNO values.

PMID- 25993060
TI  - shRNA-Mediated Silencing of Y-Box Binding Protein-1 (YB-1) Suppresses Growth of
      Neuroblastoma Cell SH-SY5Y In Vitro and In Vivo.
AB  - Y-box binding protein-1 (YB-1), a member of cold-shock protein superfamily, has
      been demonstrated to be associated with tumor malignancy, and is proposed as a
      prognostic marker in multiple carcinomas. However, the role of YB-1 in
      neuroblastoma has not been well studied. To investigate the functional role of YB
      1 in neuroblastoma, we established a YB-1-silenced neuroblastoma cell strain by
      inhibiting YB-1 expression using a shRNA knockdown approach. YB-1-silenced
      neuroblastoma SH-SY5Y cells exhibited a pronounced reduction in cell
      proliferation and an increased rate of apoptosis in vitro and in vivo xenograft
      tumor model. At molecular level, YB-1 silencing resulted in downregulation of
      Cyclin A, Cyclin D1 and Bcl-2, as well as upregulated levels of Bax, cleaved
      caspase-3 and cleaved PARP-1. We further demonstrated that YB-1 transcriptionally
      regulated Cyclin D1 expression by chromatin-immunoprecipitation and luciferase
      reporter assays. In addition, xenograft tumors derived from neuroblastoma SH-SY5Y
      cell line were treated with YB-1 shRNA plasmids by intra-tumor injection, and YB
      1 targeting effectively inhibited tumor growth and induced cell death. In
      summary, our findings suggest that YB-1 plays a critical role in neuroblastoma
      development, and it may serve as a potential target for neuroblastoma therapy. 

PMID- 25993062
TI  - Teaching patient safety in the medical undergraduate program at the Universidade
      Federal de Sao Paulo.
AB  - OBJECTIVE: To analyze the Educational Project of the undergraduate medical course
      to verify what is taught regarding Patient Safety and to enable reflections on
      the educational practice. METHODS: A descriptive study, using document research
      as strategy. The document of investigation was the Educational Project of the
      medical course, in 2006, at the Escola Paulista de Medicina of the Universidade
      Federal de Sao Paulo. The theoretical framework adopted was the Multi
      Professional Patient Safety Curriculum Guide of the World Health Organization,
      which led to the preparation of a list with 153 tracking terms. RESULTS: We
      identified 65 syllabus units in the Educational Project of the course, in which
      40 (61.5%) addressed topics related to Patient Safety. Themes on the topic
      "Infection prevention and control" were found in 19 (47.5%) units and teaching of
      "Interaction with patients and caregivers" in 12 (32.5%); however content related
      to "Learning from errors to prevent harm" were not found. None of the framework
      topics had their proposed themes entirely taught during the period of education
      of the future physicians. CONCLUSION: Patient safety is taught in a fragmented
      manner, which values clinical skills such as the diagnosis and treatment of
      diseases, post-treatment, surgical procedures, and follow-up. Since it is a
      recent movement, the teaching of patient safety confronts informative proposals
      based on traditional structures centered on subjects and on specific education,
      and it is still poorly valued.

PMID- 25993063
TI  - Cultural adaptation and reproducibility validation of the Brazilian Portuguese
      version of the Pain Assessment in Advanced Dementia (PAINAD-Brazil) scale in non
      verbal adult patients.
AB  - OBJECTIVE: To adapt the Pain Assessment in Advanced Dementia (PAINAD) scale to
      Brazilian Portuguese with respect to semantic equivalence and cultural aspects,
      and to evaluate the respective psychometric properties (validity, feasibility,
      clinical utility and inter-rater agreement). METHODS: Two-stage descriptive,
      cross-sectional retrospective study involving cultural and semantic validation of
      the Brazilian Portuguese version of the scale, and investigation of its
      psychometric properties (validity, reliability and clinical utility). The sample
      consisted of 63 inpatients presenting with neurological deficits and unable to
      self-report pain. RESULTS: Semantic and cultural validation of the PAINAD scale
      was easily achieved. The scale indicators most commonly used by nurses to assess
      pain were "Facial expression", "Body language" and "Consolability". The Brazilian
      Portuguese version of the scale has proved to be valid and accurate; good levels
      of inter-rater agreement assured reproducibility. CONCLUSION: The scale has
      proved to be useful in daily routine care of hospitalized adult and elderly
      patients in a variety of clinical settings. Short application time, ease of use,
      clear instructions and the simplicity of training required for application were
      emphasized. However, interpretation of facial expression and consolability should
      be given special attention during pain assessment training.

PMID- 25993064
TI  - Definition and application of neuropsychological test battery to evaluate
      postoperative cognitive dysfunction.
AB  - OBJECTIVE: To investigate the adequacy of the neuropsychological test battery
      proposed by the International Study of Postoperative Cognitive Dysfunction to
      evaluate this disorder in Brazilian elderly patients undergoing surgery under
      general anesthesia. METHODS: A neuropsychological assessment was made in patients
      undergoing non-cardiac surgery under general anesthesia, aged over 65 years,
      literate, with no history of psychiatric or neurological problems and score on
      the Mini Mental State Examination at or above the cutoff point for the Brazilian
      population (>18 or >23) according to the schooling level of the subject. Eighty
      patients were evaluated by a trained team of neuropsychologists up to 24 hours
      before elective surgery. RESULTS: Among the patients evaluated, one was excluded
      due to score below the cutoff point in the Mini Mental State Examination and two
      did not complete the test battery, thus remaining 77 patients in the study. The
      mean age was 69+/-7.5 years, and 62.34% of the subjects had +/-4 years of study.
      The subjects had significantly lower averages than expected (p<0.001) for
      normative tables on neuropsychological tests. CONCLUSION: The study demonstrated
      the applicability of the instruments in the Brazilian elderly and low schooling
      level population, but suggested the need to determine cutoff points appropriate
      for these individuals, ensuring the correct interpretation of results. This
      battery is relevant to postoperative follow-up evaluations, favoring the
      diagnosis of postoperative cognitive dysfunction in patients undergoing different
      types of surgery and anesthetic techniques.

PMID- 25993065
TI  - Are smoking and passive smoking related with heart rate variability in male
      adolescents?
AB  - OBJECTIVE: To analyze the relation between smoking and passive smoking with heart
      rate variability parameters in male adolescents. METHODS: The sample consisted of
      1,152 males, aged 14 and 19 years. Data related to smoking and passive smoking
      were collected using a questionnaire. RR intervals were obtained by a heart rate
      monitor, on supine position, for 10 minutes. After collecting the RR intervals,
      time (standard deviation of all RR intervals, root mean square of the squared
      differences between adjacent normal RR intervals and the percentage of adjacent
      intervals over 50ms) and frequency domains (low and high frequency and
      sympathovagal balance) parameters of heart rate variability were obtained.
      RESULTS: No significant differences between smoker and nonsmoker adolescents were
      observed in heart rate variability parameters (p>0.05). Similarly, heart rate
      variability parameters did not show significant difference between exposed and
      not exposed to passive smoking (p>0.05). CONCLUSION: Cigarette smoking and
      passive smoking are not related to heart rate variability in adolescence.

PMID- 25993066
TI  - Physical activity as a protective factor for development of non-alcoholic fatty
      liver in men.
AB  - OBJECTIVE: To determine the impact of physical activity on the prevalence of
      fatty liver, metabolic and cardiovascular disease in adult men. METHODS: This
      study evaluated 1,399 men (40.7+/-8.18 years) with body mass index of 26.7kg/m2
      (+/-3.4) who participated in the Protocol of Preventive Health Check-up at
      Hospital Israelita Albert Einstein from January to October 2011. We conducted
      tests of serum blood glucose, total cholesterol, LDL, HDL, triglycerides,
      reactive c-protein, aspartate transaminase, alanine transaminase and gamma
      glutamyl transpeptidase. The statistical analysis comprised in the comparison of
      mean and standard deviation. The analysis of variance was based in two paths of
      two way ANOVA, Student's t-test, Mann Whitney U test, Wald test and chi2. We
      considered a significance level at p<0.05 and correlation of univariate Poison
      with 95% confidence interval. RESULTS: Fatty liver was diagnosed in 37.0% of the
      sample. Triglyceride levels of active men with fatty liver were 148.2+/-77.6mg/dL
      while inactive men with fatty liver had 173.4+/-15.6mg/dL. The remaining serum
      levels were normal. Inactive individuals showed higher values than active. In
      addition, inactive individuals have 10.68 times higher risk of developing fatty
      liver compared with active. CONCLUSION: Physical activity improves metabolic
      parameters such as triglycerides, weight control, HDL, which interfere in the
      development of fatty liver. Physically active individuals had lower fatty liver
      prevalence regardless of values of body composition and lipid profile, leading
      the conclusion that physical activity has a protective role against development
      of fatty liver.

PMID- 25993067
TI  - Influence of low-level laser therapy on vertical jump in sedentary individuals.
AB  - OBJECTIVE: To investigate the effects of low intensity laser (660nm), on the
      surae triceps muscle fatigue and power, during vertical jump in sedentary
      individuals, in addition to delayed onset muscle soreness. METHODS: We included
      22 sedentary volunteers in the study, who were divided into three groups: G1
      (n=8) without performing low intensity laser (control); G2 (n=7) subjected to 6
      days of low intensity laser applications; and G3 (n=7) subjected to 10 days of
      low intensity laser applications. All subjects were evaluated by means of six
      evaluations of vertical jumps lasting 60 seconds each. In G2 and G3, laser
      applications in eight points, uniformly distributed directly to the skin in the
      region of the triceps surae were performed. Another variable analyzed was the
      delayed onset muscle soreness using the Visual Analog Scale of Pain. RESULTS:
      There was no significant difference in fatigue and mechanical power. In the
      evaluation of delayed onset muscle soreness, there was significant difference,
      being the first evaluation higher than the others. CONCLUSION: The low intensity
      laser on the triceps surae, in sedentary individuals, had no significant effects
      on the variables evaluated.

PMID- 25993068
TI  - Impact of activities in self-esteem of patients in a pulmonary rehabilitation
      program.
AB  - OBJECTIVE: To evaluate self-esteem and self-image of respiratory diseases
      patients in a Pulmonary Rehabilitation Program, who participated in socialization
      and physical fitness activities, and of patients who participated only in
      physical fitness sessions. METHODS: A descriptive cross-sectional exploratory
      study. Out of a total of 60 patients analyzed, all enrolled in the Pulmonary
      Rehabilitation Program, 42 participated in at least one of the proposed
      activities, 10 did not participate in any activity and 8 were excluded (7 were
      discharged and 1 died). RESULTS: When the two groups were compared, despite the
      fact that both demonstrated low self-esteem and self-image, the difference
      between them was relevant (p<0.05) regarding self-esteem, indicating that those
      who participated in the proposed socialization activities had better self-esteem
      than the individuals who only did the physical fitness sessions. Regarding self
      image, the difference between the groups was not relevant (p>0.05). CONCLUSION:
      The Pulmonary Rehabilitation Program patients evaluated presented low self-esteem
      and self-image; however, those carrying out some socialization activity proposed
      had better self-esteem as compared to the individuals who did only the physical
      fitness sessions.

PMID- 25993069
TI  - Cervical cancer screening in young and elderly women of the Xingu Indigenous
      Park: evaluation of the recommended screening age group in Brazil.
AB  - OBJECTIVE: To analyze the occurrence of atypia in the cytology/histology
      examinations of young women under the age of 25 years and of elderly women aged
      over 64 years, in the Xingu Indigenous Park and to evaluate, in a subjective
      manner, if the age range for screening established by the Ministry of Health and
      the Instituto Nacional de Cancer is appropriate for this population. METHODS: The
      Xingu/UNIFESP Project, in partnership with the Center for Gynecological Disease
      Prevention, develops programs to prevent cervical cancer. The exploratory,
      retrospective and descriptive study of cytological and histopathological
      examinations of young (12-24 years) and elderly (aged 64 and over) women of the
      Xingu Indigenous Park, between 2005 and 2011. RESULTS: There was low occurrence
      of cytological atypia in the elderly female population, but there were occasional
      high-grade lesions in the indigenous youth. CONCLUSION: Interrupting screening at
      the limit age of 64 years, as established by the Ministry of Health and the
      Instituto Nacional de Cancer is justified. However, screening of young women
      should begin at an earlier age.

PMID- 25993070
TI  - Perinatal outcomes in women over 40 years of age compared to those of other
      gestations.
AB  - OBJECTIVE: To clarify if older pregnant women were more likely to have adverse
      perinatal outcomes when compared to women at an ideal age to have a child.
      METHODS: The groups were divided according to age groups: under 20 years, >=20 to
      <40 years, and >=40 years. RESULTS: During the period from January 1st, 2008, to
      December 31st, 2008, there were 76 births from patients younger than 20 years and
      91 births from patients aged 40 years or over. To form a third group with
      intermediate age, the data of 92 patients aged 20 to 40 years were obtained,
      totaling 259 patients. Patients aged 40 or older had a statistically greater
      number of cesarean sections and less use of forceps or normal deliveries
      (p<0.001). The use of spinal anesthesia was statistically higher among those aged
      40 years or more (p<0.001). The frequency of male newborns was statistically
      higher in older patients, a group with statistically fewer first pregnancies
      (p<0.001). The frequency of premature newborns was statistically higher in
      patients aged 40 years or more (p=0.004). CONCLUSION: It is crucial to give
      priority to aged women, so that prenatal care will be appropriate, minimizing
      maternal complications and improving perinatal outcomes in this unique group.

PMID- 25993071
TI  - Perinatal ischemic stroke: a five-year retrospective study in a level-III
      maternity.
AB  - OBJECTIVE: To study the incidence, clinical presentation, risk factors, imaging
      diagnosis, and clinical outcome of perinatal stroke. METHODS: Data was
      retrospectively collected from full-term newborns admitted to the neonatal unit
      of a level III maternity in Lisbon with cerebral stroke, from January 2007 to
      December 2011. RESULTS: There were 11 cases of stroke: nine were arterial
      ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an
      incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous
      sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke.
      Eight patients presented with symptoms while the remaining three were
      asymptomatic and incidentally diagnosed. The most frequently registered symptoms
      (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8).
      Strokes were more commonly left-sided (9/11), and the most affected artery was
      the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive
      in most of the patients (10/11), and stroke was confirmed by cerebral magnetic
      resonance in all patients. Electroencephalographic recordings were carried out in
      five patients and were abnormal in three (focal abnormalities n=2, burst
      suppression pattern n=1). Eight patients had previously identified risk factors
      for neonatal stroke which included obstetric and neonatal causes. Ten patients
      were followed up at outpatients setting; four patients developed motor deficits
      and one presented with epilepsy. CONCLUSIONS: Although a modest and heterogeneous
      sample, this study emphasizes the need for a high level of suspicion when it
      comes to neonatal stroke, primarily in the presence of risk factors. The
      prevalence of neurological sequelae in our series supports the need of long-term
      follow-up and early intervention strategies.

PMID- 25993072
TI  - Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1
      adipocytes.
AB  - OBJECTIVE: To study the effect of different doses of triiodothyronine on gene
      expression of the adipokines leptin and adiponectin, at different times, and to
      evaluate the difference in expression between the two adipokines in each group.
      METHODS: 3T3-L1 adipocytes were incubated with triiodothyronine at physiological
      dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without
      triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin
      mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way
      analyses of variance, Tukey's test or Student's t test, were used to analyze
      data, and significance level was set at 5%. RESULTS: Leptin levels decreased in
      the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM
      dose group, but increased at the 100nM dose. After 6 hours, both genes were
      suppressed in all hormone concentrations. After 24 hours, leptin levels increased
      at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin
      levels increased only in the 100nM group as compared to the control group.
      CONCLUSION: These results demonstrated fast actions of triiodothyronine on the
      leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for
      leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the
      expression of adipokines in adipocytes at different times and doses which may be
      useful to assist in the treatment of obesity, assuming that leptin is increased
      and adiponectin is decreased, in obesity cases.

PMID- 25993073
TI  - Superoxide overproduction and kidney fibrosis: a new animal model.
AB  - OBJECTIVE: To establish whether the mutation in the Immp2L gene induces renal
      fibrosis and whether aging exacerbates renal morphology in mice. METHODS: Female
      mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like
      protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using
      classic fibrosis score, Masson's trichrome staining, and analysis of profibrotic
      markers using real time polymerase chain reaction (superoxide dismutase 1,
      metalloproteinase-9, erythropoietin, transforming growth factor beta), and
      immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were
      determined by immunohistochemistry. The number of renal apoptotic cells was
      determined. Renal function was estimated by serum creatinine. RESULTS: Young
      mutant mice had significantly more glomerulosclerosis than age-matched mice
      (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition
      (p=0.019), and collagen type IV expression (p<0.001). Superoxide dismutase 1
      expression was significantly higher in young mutants (p=0.038). Old mutants
      exhibited significantly higher expression of the fibroblast marker and macrophage
      marker (p=0.007 and p=0.012, respectively). The real time polymerase chain
      reaction of metalloproteinase-9 and erythropoietin were enhanced 2.5- and 6-fold,
      respectively, in old mutants. Serum creatinine was significantly higher in old
      mutants (p<0.001). CONCLUSION: This mutation altered renal architecture by
      increasing the deposition of extracellular matrix, oxidative stress, and
      inflammation, suggesting a protective role of Immp2L against renal fibrosis.

PMID- 25993074
TI  - Cells involved in extracellular matrix remodeling after acute myocardial
      infarction.
AB  - OBJECTIVE: Evaluate the effects of VEGF165 gene transfer in the process of
      remodeling of the extracellular matrix after an acute myocardial infarct.
      METHODS: Wistar rats were submitted to myocardial infarction, after the ligation
      of the left descending artery, and the left ventricle ejection fraction was used
      to classify the infarcts into large and small. The animals were divided into
      groups of ten, according to the size of infarcted area (large or small), and
      received or not VEGF165 treatment. Evaluation of different markers was performed
      using immunohistochemistry and digital quantification. The primary antibodies
      used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E
      cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were
      expressed as mean and standard error, and analyzed by ANOVA, considering
      statistically significant if p<=0.05. RESULTS: There was a significant increase
      in the expression of undifferentiated cell markers, such as fibronectin (protein
      present in the extracellular matrix) and CD44 (glycoprotein present in the
      endothelial cells). However, there was decreased expression of vimentin and PCNA,
      indicating a possible decrease in the process of cell proliferation after
      treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion
      protein between myocardial cells), CD24 (protein present in the blood vessels),
      and alpha-1-actin (specific myocyte marker), showed higher expression in the
      groups submitted to gene therapy, compared to non-treated group. The value
      obtained by the relation between alpha-1-actin and vimentin was approximately
      three times higher in the groups treated with VEGF165, suggesting greater tissue
      differentiation. CONCLUSION: The results demonstrated the important role of
      myocytes in the process of tissue remodeling, confirming that VEGF165 seems to
      provide a protective effect in the treatment of acute myocardial infarct.

PMID- 25993075
TI  - Impact of implementing an Internal Bed Regulation Committee on administrative and
      care indicators at a teaching hospital.
AB  - OBJECTIVE: To compare hospital indicators before and after implementing an
      Internal Bed Regulation Committee at a reference hospital. METHODS: It is an
      quantitative, evaluation, exploratory, descriptive and cross-sectional research.
      The data was gathered from the hospital administrative reports for the period
      2008-2013, provided by the Information Technology Center of the Complexo FAMEMA.
      RESULTS: The indicators improved after implementation of the Internal Bed
      Regulation Committee. CONCLUSION: The individuals involved in the process
      acknowledged the improvement. It is necessary to carry on the regulatory actions,
      especially in a comprehensive and complex healthcare system, such as the
      brazilian Sistema Unico de Saude.

PMID- 25993076
TI  - Storiform collagenoma: case report.
AB  - Storiform collagenoma is a rare tumor, which originates from the proliferation of
      fibroblasts that show increased production of type-I collagen. It is usually
      found in the face, neck and extremities, but it can also appear in the trunk,
      scalp and, less frequently, in the oral mucosa and the nail bed. It affects both
      sexes, with a slight female predominance. It may be solitary or multiple, the
      latter being an important marker for Cowden syndrome. It presents as a painless,
      solid nodular tumor that is slow-growing. It must be considered in the
      differential diagnosis of other well-circumscribed skin lesions, such as
      dermatofibroma, pleomorphic fibroma, sclerotic lipoma, fibrolipoma, giant cell
      collagenoma, benign fibrous histiocytoma, intradermal Spitz nevus and giant cell
      angiohistiocytoma. 

PMID- 25993077
TI  - Posttraumatic eyebrow reconstruction with hair-bearing temporoparietal fascia
      flap.
AB  - The temporoparietal fascia flap has been extensively used in craniofacial
      reconstructions. However, its use for eyebrow reconstruction has been
      sporadically reported. We describe a successfully repaired hair-bearing
      temporoparietal fascia flap after traumatic avulsion of eyebrow. Temporoparietal
      fascia flap is a versatile tool and should be considered as a therapeutic option
      by all plastic surgeons. 

PMID- 25993078
TI  - Preimplantation genetic diagnosis for cystic fibrosis: a case report.
AB  - Cystic fibrosis is an autosomal recessive disorder caused by mutations in the
      cystic fibrosis transmembrane conductance regulator gene. This disorder produces
      a variable phenotype including lung disease, pancreatic insufficiency, and
      meconium ileus plus bilateral agenesis of the vas deferens causing obstructive
      azoospermia and male infertility. Preimplantation genetic diagnosis is an
      alternative that allows identification of embryos affected by this or other
      genetic diseases. We report a case of couple with cystic fibrosis; the woman had
      the I148 T mutation and the man had the Delta F508 gene mutation. The couple
      underwent in vitro fertilization, associated with preimplantation genetic
      diagnosis, and with subsequent selection of healthy embryos for uterine transfer.
      The result was an uneventful pregnancy and delivery of a healthy male baby. 

PMID- 25993079
TI  - Ischemia and reperfusion injury in renal transplantation: hemodynamic and
      immunological paradigms.
AB  - Ischemia and reperfusion injury is an inevitable event in renal transplantation.
      The most important consequences are delayed graft function, longer length of
      stay, higher hospital costs, high risk of acute rejection, and negative impact of
      long-term follow-up. Currently, many factors are involved in their
      pathophysiology and could be classified into two different paradigms for
      education purposes: hemodynamic and immune. The hemodynamic paradigm is described
      as the reduction of oxygen delivery due to blood flow interruption, involving
      many hormone systems, and oxygen-free radicals produced after reperfusion. The
      immune paradigm has been recently described and involves immune system cells,
      especially T cells, with a central role in this injury. According to these
      concepts, new strategies to prevent ischemia and reperfusion injury have been
      studied, particularly the more physiological forms of storing the kidney, such as
      the pump machine and the use of antilymphocyte antibody therapy before
      reperfusion. Pump machine perfusion reduces delayed graft function prevalence and
      length of stay at hospital, and increases long-term graft survival. The use of
      antilymphocyte antibody therapy before reperfusion, such as ThymoglobulinTM, can
      reduce the prevalence of delayed graft function and chronic graft dysfunction. 

PMID- 25993080
TI  - Intestinal and multivisceral transplantation.
AB  - Intestinal transplantation has shown exceptional growth over the past 10 years.
      At the end of the 1990's, intestinal transplantation moved out of the
      experimental realm to become a routine practice in treating patients with severe
      complications related to total parenteral nutrition and intestinal failure. In
      the last years, several centers reported an increasing improvement in survival
      outcomes (about 80%), during the first 12 months after surgery, but long-term
      survival is still a challenge. Several advances led to clinical application of
      transplants. Immunosuppression involved in intestinal and multivisceral
      transplantation was the biggest gain for this procedure in the past decade due to
      tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte
      antibodies. Despite the advancement of rigid immunosuppression protocols,
      rejection is still very frequent in the first 12 months, and can result in long
      term graft loss. The future of intestinal transplantation and multivisceral
      transplantation appears promising. The major challenge is early recognition of
      acute rejection in order to prevent graft loss, opportunistic infections
      associated to complications, post-transplant lymphoproliferative disease and
      graft versus host disease; and consequently, improve results in the long run. 

PMID- 25993081
TI  - Cytomegalovirus infection in renal transplantation: clinical aspects, management
      and the perspectives.
AB  - Cytomegalovirus infection is one of most frequent infectious complications after
      renal transplantation, and can be classified as primo-infection, when the
      transmission occurs through the graft, or reactivation, when the recipient is
      cytomegalovirus seropositive. After transplantation, cytomegalovirus can appear
      as an infection, when the patient presents with evidence of viral replication
      without symptoms or disease, which has two clinical spectra: typical viral
      syndrome or invasive disease, which is a less common form. Their effects can be
      classified as direct, while the disease is developed, or indirect, with an
      increase of acute rejection and chronic allograft dysfunction risks. Diagnosis
      must be made based on viremia by one of the standardized methods: antigenemia or
      PCR, which is more sensitive. The risk factors related to infection after
      transplantation are the serologic matching (positive donor and negative
      recipient) and anti-lymphocyte antibody drugs. One of the strategies to reduce
      risk of disease should be chosen for patients at high risk: preemptive treatment
      or universal prophylaxis. Recent clinical research has described ganciclovir
      resistance as an emergent problem in management of cytomegalovirus infection. Two
      types of mutation that cause resistance were described: UL97 (most frequent) and
      UL54. Today, sophisticated methods of immunologic monitoring to detect specific T
      cell clones against cytomegalovirus are used in clinical practice to improve the
      management of high-risk patients after renal transplantation. 

PMID- 25993082
TI  - Liver transplantation: history, outcomes and perspectives.
AB  - In 1958 Francis Moore described the orthotopic liver transplantation technique in
      dogs. In 1963, Starzl et al. performed the first liver transplantation. In the
      first five liver transplantations no patient survived more than 23 days. In 1967,
      stimulated by Calne who used antilymphocytic serum, Starzl began a successful
      series of liver transplantation. Until 1977, 200 liver transplantations were
      performed in the world. In that period, technical problems were overcome. Roy
      Calne, in 1979, used the first time cyclosporine in two patients who had
      undergone liver transplantation. In 1989, Starzl et al. reported a series of
      1,179 consecutives patients who underwent liver transplantation and reported a
      survival rate between one and five years of 73% and 64%, respectively. Finally,
      in 1990, Starzl et al. reported successful use of tacrolimus in patents
      undergoing liver transplantation and who had rejection despite receiving
      conventional immunosuppressive treatment. Liver Transplantation Program was
      initiated at Hospital Israelita Albert Einstein in 1990 and so far over 1,400
      transplants have been done. In 2013, 102 deceased donors liver transplantations
      were performed. The main indications for transplantation were hepatocellular
      carcinoma (38%), hepatitis C virus (33.3%) and alcohol liver cirrhosis (19.6%).
      Of these, 36% of patients who underwent transplantation showed biological MELD
      score > 30. Patient and graft survival in the first year was, 82.4% and 74.8%,
      respectively. A major challenge in liver transplantation field is the
      insufficient number of donors compared with the growing demand of transplant
      candidates. Thus, we emphasize that appropriated donor/receptor selection,
      allocation and organ preservation topics should contribute to improve the number
      and outcomes in liver transplantation. 

PMID- 25993083
TI  - Congenital fibrovascular pupillary membrane.

PMID- 25993084
TI  - Patient with Morning Glory syndrome.

PMID- 25993086
TI  - Ethics Requirement Score.

PMID- 25993085
TI  - Interventional radiology and endovascular surgery in the treatment of ectopic
      pregnancies.
AB  - The advent of interventional radiology enabled remarkable advances in diagnosis
      and treatment of several situations in obstetrics and gynecology. In the field of
      obstetrics, these advances include temporary occlusion of the iliac arteries to
      the management of placenta accreta and/or prior, arteriovenous fistulas after
      embolization of uterine curettage and management of ectopic uterine and extra
      uterine pregnancies. The non-tubal ectopic pregnancy, either cervical, abdominal,
      ovarian or in a cesarean scar, often represents major therapeutic challenge,
      especially when exists a desire to maintain fertility. Despite the systemic
      methotrexate therapy and surgical resection of the ectopic gestational sac be the
      most used therapeutic options, the interventionist approach of non-tubal ectopic
      pregnancies, direct injection of methotrexate in the gestational sac and intra
      arterial chemoembolization of uterine arteries constitute in the currently
      literature viable, safe, effective modalities with low morbidity, shorter
      hospital stay, and rapid clinical recovery. Because of little variety of
      materials used, and the increase in training of specialists in the area, the
      radiological intervention as a treatment option in ectopic pregnancies is
      financially viable and present considerable accessibility in the world and at
      most of Brazilian medical centers. 

PMID- 25993087
TI  - Teaching sexuality in Brazilian medical schools.

PMID- 25993088
TI  - Core-Shell CdS-Cu2S Nanorod Array Solar Cells.
AB  - As an earth-abundant p-type semiconductor, copper sulfide (Cu2S) is an attractive
      material for application in photovoltaic devices. However, it suffers from a
      minority carrier diffusion length that is less than the length required for
      complete light absorption. Core-shell nanowires and nanorods have the potential
      to alleviate this difficulty because they decouple the length scales of light
      absorption and charge collection. To achieve this geometry using Cu2S, cation
      exchange was applied to an array of CdS nanorods to produce well-defined CdS-Cu2S
      core-shell nanorods. Previous work has demonstrated single-nanowire photovoltaic
      devices from this material system, but in this work, the cation exchange
      chemistry has been applied to nanorod arrays to produce ensemble-level devices
      with microscale sizes. The core-shell nanorod array devices show power conversion
      efficiencies of up to 3.8%. In addition, these devices are stable when measured
      in air after nearly one month of storage in a desiccator. These results are a
      first step in the development of large-area nanostructured Cu2S-based
      photovoltaics that can be processed from solution. 

PMID- 25993089
TI  - Effects of Large-Scale Releases on the Genetic Structure of Red Sea Bream (Pagrus
      major, Temminck et Schlegel) Populations in Japan.
AB  - Large-scale hatchery releases are carried out for many marine fish species
      worldwide; nevertheless, the long-term effects of this practice on the genetic
      structure of natural populations remains unclear. The lack of knowledge is
      especially evident when independent stock enhancement programs are conducted
      simultaneously on the same species at different geographical locations, as occurs
      with red sea bream (Pagrus major, Temminck et Schlegel) in Japan. In this study,
      we examined the putative effects of intensive offspring releases on the genetic
      structure of red sea bream populations along the Japanese archipelago by
      genotyping 848 fish at fifteen microsatellite loci. Our results suggests weak but
      consistent patterns of genetic divergence (F(ST) = 0.002, p < 0.001). Red sea
      bream in Japan appeared spatially structured with several patches of distinct
      allelic composition, which corresponded to areas receiving an important influx of
      fish of hatchery origin, either released intentionally or from unintentional
      escapees from aquaculture operations. In addition to impacts upon local
      populations inhabiting semi-enclosed embayments, large-scale releases (either
      intentionally or from unintentional escapes) appeared also to have perturbed
      genetic structure in open areas. Hence, results of the present study suggest that
      independent large-scale marine stock enhancement programs conducted
      simultaneously on one species at different geographical locations may compromise
      native genetic structure and lead to patchy patterns in population genetic
      structure.

PMID- 25993090
TI  - The first dinosaur from Washington State and a review of Pacific coast dinosaurs
      from North America.
AB  - We describe the first diagnostic dinosaur fossil from Washington State. The
      specimen, which consists of a proximal left femur, was recovered from the shallow
      marine rocks of the Upper Cretaceous (Campanian) Cedar District Formation
      (Nanaimo Group) and is interpreted as pertaining to a large theropod on the basis
      of its hollow medullary cavity and proximally placed fourth trochanter. The
      Washington theropod represents one of the northernmost occurrences of a Mesozoic
      dinosaur on the west coast of the United States and one of only a handful from
      the Pacific coast of Laramidia during the Cretaceous. Its isolated nature and
      preservation in marine rocks suggest that the element was washed in from a nearby
      fluvial system. If the femur pertains to a tyrannosauroid, which seems likely
      given its size and the widespread occurrence of the group across Laramidia during
      Late Cretaceous times, then it would represent an earlier occurrence of large
      body size than previously recognized (complete femur length estimated at 1.2
      meters). Uncertainty surrounding the latitude of deposition of the Nanaimo Group
      (i.e., the Baja-British Columbia hypothesis) precludes assigning the Washington
      theropod to either of the putative northern or southern biogeographic provinces
      of Laramidia. 

PMID- 25993091
TI  - Cellular signalling effects in high precision radiotherapy.
AB  - Radiotherapy is commonly planned on the basis of physical dose received by the
      tumour and surrounding normal tissue, with margins added to address the
      possibility of geometric miss. However, recent experimental evidence suggests
      that intercellular signalling results in a given cell's survival also depending
      on the dose received by neighbouring cells. A model of radiation-induced cell
      killing and signalling was used to analyse how this effect depends on dose and
      margin choices. Effective Uniform Doses were calculated for model tumours in both
      idealised cases with no delivery uncertainty and more realistic cases
      incorporating geometric uncertainty. In highly conformal irradiation, a lack of
      signalling from outside the target leads to reduced target cell killing,
      equivalent to under-dosing by up to 10% compared to large uniform fields. This
      effect is significantly reduced when higher doses per fraction are considered,
      both increasing the level of cell killing and reducing margin sensitivity. These
      effects may limit the achievable biological precision of techniques such as
      stereotactic radiotherapy even in the absence of geometric uncertainties,
      although it is predicted that larger fraction sizes reduce the relative
      contribution of cell signalling driven effects. These observations may contribute
      to understanding the efficacy of hypo-fractionated radiotherapy. 

PMID- 25993092
TI  - A general method for interconversion of boronic acid protecting groups:
      trifluoroborates as common intermediates.
AB  - We have developed a general protocol for the interconversion of diverse protected
      boronic acids, via intermediate organotrifluoroborates. N-Methyliminodiacetyl
      boronates, which have been hitherto resistant to direct conversion to
      trifluoroborates, have been shown to undergo fluorolysis at elevated
      temperatures. Subsequent solvolysis of organotrifluoroborates in the presence of
      trimethylsilyl chloride and a wide range of bis-nucleophiles enables the
      generation of a variety of protected boronic acids. 

PMID- 25993093
TI  - Potassium Retention under Salt Stress Is Associated with Natural Variation in
      Salinity Tolerance among Arabidopsis Accessions.
AB  - Plants are exposed to various environmental stresses during their life cycle such
      as salt, drought and cold. Natural variation mediated plant growth adaptation has
      been employed as an effective approach in response to the diverse environmental
      cues such as salt stress. However, the molecular mechanism underlying this
      process is not well understood. In the present study, a collection of 82
      Arabidopsis thaliana accessions (ecotypes) was screened with a view to identify
      variation for salinity tolerance. Seven accessions showed a higher level of
      tolerance than Col-0. The young seedlings of the tolerant accessions demonstrated
      a higher K(+) content and a lower Na(+)/K(+) ratio when exposed to salinity
      stress, but its Na(+) content was the same as that of Col-0. The K(+) transporter
      genes AtHAK5, AtCHX17 and AtKUP1 were up-regulated significantly in almost all
      the tolerant accessions, even in the absence of salinity stress. There was little
      genetic variation or positive transcriptional variation between the selections
      and Col-0 with respect to Na+-related transporter genes, as AtSOS genes, AtNHX1
      and AtHKT1;1. In addition, under salinity stress, these selections accumulated
      higher compatible solutes and lower reactive oxygen species than did Col-0. Taken
      together, our results showed that natural variation in salinity tolerance of
      Arabidopsis seems to have been achieved by the strong capacity of K(+) retention.

PMID- 25993094
TI  - Origin and Population Dynamics of a Novel HIV-1 Subtype G Clade Circulating in
      Cape Verde and Portugal.
AB  - The human immunodeficiency virus type 1 (HIV-1) subtype G is the most prevalent
      and second most prevalent HIV-1 clade in Cape Verde and Portugal, respectively;
      but there is no information about the origin and spatiotemporal dispersal pattern
      of this HIV-1 clade circulating in those countries. To this end, we used Maximum
      Likelihood and Bayesian coalescent-based methods to analyze a collection of 578
      HIV-1 subtype G pol sequences sampled throughout Portugal, Cape Verde and 11
      other countries from West and Central Africa over a period of 22 years (1992 to
      2013). Our analyses indicate that most subtype G sequences from Cape Verde (80%)
      and Portugal (95%) branched together in a distinct monophyletic cluster (here
      called G(CV-PT)). The G(CV-PT) clade probably emerged after a single migration of
      the virus out of Central Africa into Cape Verde between the late 1970s and the
      middle 1980s, followed by a rapid dissemination to Portugal a couple of years
      later. Reconstruction of the demographic history of the G(CV-PT) clade
      circulating in Cape Verde and Portugal indicates that this viral clade displayed
      an initial phase of exponential growth during the 1980s and 1990s, followed by a
      decline in growth rate since the early 2000s. Our data also indicate that during
      the exponential growth phase the G(CV-PT) clade recombined with a preexisting
      subtype B viral strain circulating in Portugal, originating the CRF14_BG clade
      that was later disseminated to Spain and Cape Verde. Historical and recent human
      population movements between Angola, Cape Verde and Portugal probably played a
      key role in the origin and dispersal of the G(CV-PT )and CRF14_BG clades.

PMID- 25993095
TI  - Ultra-high-throughput screening of an in vitro-synthesized horseradish peroxidase
      displayed on microbeads using cell sorter.
AB  - The C1a isoenzyme of horseradish peroxidase (HRP) is an industrially important
      heme-containing enzyme that utilizes hydrogen peroxide to oxidize a wide variety
      of inorganic and organic compounds for practical applications, including
      synthesis of fine chemicals, medical diagnostics, and bioremediation. To develop
      a ultra-high-throughput screening system for HRP, we successfully produced active
      HRP in an Escherichia coli cell-free protein synthesis system, by adding
      disulfide bond isomerase DsbC and optimizing the concentrations of hemin and
      calcium ions and the temperature. The biosynthesized HRP was fused with a single
      chain Cro (scCro) DNA-binding tag at its N-terminal and C-terminal sites. The
      addition of the scCro-tag at both ends increased the solubility of the protein.
      Next, HRP and its fusion proteins were successfully synthesized in a water
      droplet emulsion by using hexadecane as the oil phase and SunSoft No. 818SK as
      the surfactant. HRP fusion proteins were displayed on microbeads attached with
      double-stranded DNA (containing the scCro binding sequence) via scCro-DNA
      interactions. The activities of the immobilized HRP fusion proteins were detected
      with a tyramide-based fluorogenic assay using flow cytometry. Moreover, a model
      microbead library containing wild type hrp (WT) and inactive mutant (MUT) genes
      was screened using fluorescence-activated cell-sorting, thus efficiently
      enriching the WT gene from the 1:100 (WT:MUT) library. The technique described
      here could serve as a novel platform for the ultra-high-throughput discovery of
      more useful HRP mutants and other heme-containing peroxidases. 

PMID- 25993096
TI  - Temporal changes in rat liver gene expression after acute cadmium and chromium
      exposure.
AB  - U.S. Service Members and civilians are at risk of exposure to a variety of
      environmental health hazards throughout their normal duty activities and in
      industrial occupations. Metals are widely used in large quantities in a number of
      industrial processes and are a common environmental toxicant, which increases the
      possibility of being exposed at toxic levels. While metal toxicity has been
      widely studied, the exact mechanisms of toxicity remain unclear. In order to
      further elucidate these mechanisms and identify candidate biomarkers, rats were
      exposed via a single intraperitoneal injection to three concentrations of CdCl2
      and Na(2)Cr(2)O(7), with livers harvested at 1, 3, or 7 days after exposure. Cd
      and Cr accumulated in the liver at 1 day post exposure. Cd levels remained
      elevated over the length of the experiment, while Cr levels declined. Metal
      exposures induced ROS, including hydroxyl radical (*OH), resulting in DNA strand
      breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to
      increase with time post-exposure in both metals, despite declines in Cr levels.
      Differentially expressed genes were identified via microarray analysis. Both
      metals perturbed gene expression in pathways related to oxidative stress,
      metabolism, DNA damage, cell cycle, and inflammatory response. This work provides
      insight into the temporal effects and mechanistic pathways involved in acute
      metal intoxication, leading to the identification of candidate biomarkers.

PMID- 25993097
TI  - Histone demethylation maintains Prdm14 and Tsix expression and represses xIst in
      embryonic stem cells.
AB  - Epigenetic reprogramming is exemplified by the remarkable changes observed in
      cellular differentiation and X-chromosome inactivation (XCI) in mammalian female
      cells. Histone 3 lysine 27 trimethylation (H3K27me3) is a modification that
      suppresses gene expression in multiple contexts including embryonic stem cells
      (ESCs) and decorates the entire inactive X-chromosome. The conversion of female
      somatic cells to induced pluripotency is accompanied by X-chromosome reactivation
      (XCR) and H3K27me3 erasure. Here, we show that the H3K27-specific demethylase Utx
      regulates the expression of the master regulators for XCI and XCR: Prdm14, Tsix,
      and Xist. Female ESC transcriptome analysis using a small molecule inhibitor for
      H3K27 demethylases, GSK-J4, identifies novel targets of H3K27 demethylation.
      Consistent with a recent report that GSK-J4 can inhibit other histone
      demethylase, we found that elevated H3K4me3 levels are associated with increased
      gene expression including Xist. Our data suggest multiple regulatory mechanisms
      for XCI via histone demethylation. 

PMID- 25993098
TI  - MicroRNA Expression Profile in Bovine Granulosa Cells of Preovulatory Dominant
      and Subordinate Follicles during the Late Follicular Phase of the Estrous Cycle.
AB  - In bovine, ovarian follicles grow in a wave-like fashion with commonly 2 or 3
      follicular waves emerging per estrous cycle. The dominant follicle of the
      follicular wave which coincides with the LH-surge becomes ovulatory, leaving the
      subordinate follicles to undergo atresia. These physiological processes are
      controlled by timely and spatially expressed genes and gene products, which in
      turn are regulated by post-transcriptional regulators. MicroRNAs, a class of
      short non-coding RNA molecules, are one of the important posttranscriptional
      regulators of genes associated with various cellular processes. Here we
      investigated the expression pattern of miRNAs in granulosa cells of bovine
      preovulatory dominant and subordinate follicles during the late follicular phase
      of bovine estrous cycle using Illumina miRNA deep sequencing. In addition to 11
      putative novel miRNAs, a total of 315 and 323 known miRNAs were detected in
      preovulatory dominant and subordinate follicles, respectively. Moreover, in
      comparison with the subordinate follicles, a total of 64 miRNAs were found to be
      differentially expressed in preovulatory dominant follicles, of which 34 miRNAs
      including the miR-132 and miR-183 clusters were significantly enriched, and 30
      miRNAs including the miR-17-92 cluster, bta-miR-409a and bta-miR-378 were
      significantly down regulated in preovulatory dominant follicles. In-silico
      pathway analysis revealed that canonical pathways related to oncogenesis, cell
      adhesion, cell proliferation, apoptosis and metabolism were significantly
      enriched by the predicted target genes of differentially expressed miRNAs.
      Furthermore, Luciferase reporter assay analysis showed that one of the
      differentially regulated miRNAs, the miR-183 cluster miRNAs, were validated to
      target the 3'-UTR of FOXO1 gene. Moreover FOXO1 was highly enriched in granulosa
      cells of subordinate follicles in comparison with the preovulatory dominant
      follicles demonstrating reciprocal expression pattern with miR-183 cluster
      miRNAs. In conclusion, the presence of distinct sets of miRNAs in granulosa cells
      of preovulatory dominant and subordinate follicles supports the potential role of
      miRNAs in post-transcriptional regulation of genes involved in bovine follicular
      development during the late follicular phase of the estrous cycle.

PMID- 25993099
TI  - Evaluation by Expert Dancers of a Robot That Performs Partnered Stepping via
      Haptic Interaction.
AB  - Our long-term goal is to enable a robot to engage in partner dance for use in
      rehabilitation therapy, assessment, diagnosis, and scientific investigations of
      two-person whole-body motor coordination. Partner dance has been shown to improve
      balance and gait in people with Parkinson's disease and in older adults, which
      motivates our work. During partner dance, dance couples rely heavily on haptic
      interaction to convey motor intent such as speed and direction. In this paper, we
      investigate the potential for a wheeled mobile robot with a human-like upper-body
      to perform partnered stepping with people based on the forces applied to its end
      effectors. Blindfolded expert dancers (N=10) performed a forward/backward walking
      step to a recorded drum beat while holding the robot's end effectors. We varied
      the admittance gain of the robot's mobile base controller and the stiffness of
      the robot's arms. The robot followed the participants with low lag (M=224, SD=194
      ms) across all trials. High admittance gain and high arm stiffness conditions
      resulted in significantly improved performance with respect to subjective and
      objective measures. Biomechanical measures such as the human hand to human
      sternum distance, center-of-mass of leader to center-of-mass of follower (CoM
      CoM) distance, and interaction forces correlated with the expert dancers'
      subjective ratings of their interactions with the robot, which were internally
      consistent (Cronbach's alpha=0.92). In response to a final questionnaire, 1/10
      expert dancers strongly agreed, 5/10 agreed, and 1/10 disagreed with the
      statement "The robot was a good follower." 2/10 strongly agreed, 3/10 agreed, and
      2/10 disagreed with the statement "The robot was fun to dance with." The
      remaining participants were neutral with respect to these two questions. 

PMID- 25993101
TI  - The Escherichia coli Envelope Stress Sensor CpxA Responds to Changes in Lipid
      Bilayer Properties.
AB  - The Cpx stress response system is induced by various environmental and cellular
      stimuli. It is also activated in Escherichia coli strains lacking the major
      phospholipid, phosphatidylethanolamine (PE). However, it is not known whether
      CpxA directly senses changes in the lipid bilayer or the presence of misfolded
      proteins due to the lack of PE in their membranes. To address this question, we
      used an in vitro reconstitution system and vesicles with different lipid
      compositions to track modulations in the activity of CpxA in different lipid
      bilayers. Moreover, the Cpx response was validated in vivo by monitoring
      expression of a PcpxP-gfp reporter in lipid-engineered strains of E. coli. Our
      combined data indicate that CpxA responds specifically to different lipid
      compositions. 

PMID- 25993100
TI  - The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in
      an Aerosol Model of Infection.
AB  - Burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis
      glanders. Previous studies indicated that the genome of the organism contains
      eight genes specifying autotransporter proteins, which are important virulence
      factors of Gram-negative bacteria. In the present study, we report the
      characterization of one of these autotransporters, BpaB. Database searches
      identified the bpaB gene in ten B. mallei isolates and the predicted proteins
      were 99-100% identical. Comparative sequence analyses indicate that the gene
      product is a trimeric autotransporter of 1,090 amino acids with a predicted
      molecular weight of 105-kDa. Consistent with this finding, we discovered that
      recombinant bacteria expressing bpaB produce a protein of >= 300-kDa on their
      surface that is reactive with a BpaB-specific monoclonal antibody. Analysis of
      sera from mice infected with B. mallei indicated that animals produce antibodies
      against BpaB during the course of disease, thus establishing production of the
      autotransporter in vivo. To gain insight on its role in virulence, we inactivated
      the bpaB gene of B. mallei strain ATCC 23344 and determined the median lethal
      dose of the mutant in a mouse model of aerosol infection. These experiments
      revealed that the bpaB mutation attenuates virulence 8-14 fold. Using a crystal
      violet-based assay, we also discovered that constitutive production of BpaB on
      the surface of B. mallei promotes biofilm formation. To our knowledge, this is
      the first report of a biofilm factor for this organism.

PMID- 25993102
TI  - Estimating risks of heat strain by age and sex: a population-level simulation
      model.
AB  - Individuals living in hot climates face health risks from hyperthermia due to
      excessive heat. Heat strain is influenced by weather exposure and by individual
      characteristics such as age, sex, body size, and occupation. To explore the
      population-level drivers of heat strain, we developed a simulation model that
      scales up individual risks of heat storage (estimated using Myrup and Morgan's
      man model "MANMO") to a large population. Using Australian weather data, we
      identify high-risk weather conditions together with individual characteristics
      that increase the risk of heat stress under these conditions. The model
      identifies elevated risks in children and the elderly, with females aged 75 and
      older those most likely to experience heat strain. Risk of heat strain in males
      does not increase as rapidly with age, but is greatest on hot days with high
      solar radiation. Although cloudy days are less dangerous for the wider
      population, older women still have an elevated risk of heat strain on hot cloudy
      days or when indoors during high temperatures. Simulation models provide a
      valuable method for exploring population level risks of heat strain, and a tool
      for evaluating public health and other government policy interventions. 

PMID- 25993103
TI  - Heat waves and morbidity: current knowledge and further direction-a comprehensive
      literature review.
AB  - In the past few decades, several devastating heat wave events have significantly
      challenged public health. As these events are projected to increase in both
      severity and frequency in the future, it is important to assess the relationship
      between heat waves and the health indicators that can be used in the early
      warning systems to guide the public health response. Yet there is a knowledge gap
      in the impact of heat waves on morbidity. In this study, a comprehensive review
      was conducted to assess the relationship between heat waves and different
      morbidity indicators, and to identify the vulnerable populations. The PubMed and
      ScienceDirect database were used to retrieve published literature in English from
      1985 to 2014 on the relationship between heat waves and morbidity, and the
      following MeSH terms and keywords were used: heat wave, heat wave, morbidity,
      hospital admission, hospitalization, emergency call, emergency medical services,
      and outpatient visit. Thirty-three studies were included in the final analysis.
      Most studies found a short-term negative health impact of heat waves on
      morbidity. The elderly, children, and males were more vulnerable during heat
      waves, and the medical care demand increased for those with existing chronic
      diseases. Some social factors, such as lower socioeconomic status, can contribute
      to heat-susceptibility. In terms of study methods and heat wave definitions,
      there remain inconsistencies and uncertainties. Relevant policies and guidelines
      need to be developed to protect vulnerable populations. Morbidity indicators
      should be adopted in heat wave early warning systems in order to guide the
      effective implementation of public health actions. 

PMID- 25993104
TI  - The negative affect hypothesis of noise sensitivity.
AB  - Some studies indicate that noise sensitivity is explained by negative affect, a
      dispositional tendency to negatively evaluate situations and the self.
      Individuals high in such traits may report a greater sensitivity to other sensory
      stimuli, such as smell, bright light and pain. However, research investigating
      the relationship between noise sensitivity and sensitivity to stimuli associated
      with other sensory modalities has not always supported the notion of a common
      underlying trait, such as negative affect, driving them. Additionally, other
      explanations of noise sensitivity based on cognitive processes have existed in
      the clinical literature for over 50 years. Here, we report on secondary analyses
      of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing
      on the relationship between noise sensitivity to and annoyance with a variety of
      olfactory-related stimuli. In the first study a correlational design examined the
      relationships between noise sensitivity, noise annoyance, and perceptual ratings
      of 16 odors. The second study sought differences between mean noise and air
      pollution annoyance scores across noise sensitivity categories. Results from both
      analyses failed to support the notion that, by itself, negative affectivity
      explains sensitivity to noise. 

PMID- 25993106
TI  - MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in
      Drosophila Follicle Cells.
AB  - RNA interference-related silencing mechanisms concern very diverse and distinct
      biological processes, from gene regulation (via the microRNA pathway) to defense
      against molecular parasites (through the small interfering RNA and the Piwi
      interacting RNA pathways). Small non-coding RNAs serve as specificity factors
      that guide effector proteins to ribonucleic acid targets via base-pairing
      interactions, to achieve transcriptional or post-transcriptional regulation.
      Because of the small sequence complementarity required for microRNA-dependent
      post-transcriptional regulation, thousands of microRNA (miRNA) putative targets
      have been annotated in Drosophila. In Drosophila somatic ovarian cells, genomic
      parasites, such as transposable elements (TEs), are transcriptionally repressed
      by chromatin changes induced by Piwi-interacting RNAs (piRNAs) that prevent them
      from invading the germinal genome. Here we show, for the first time, that a
      functional miRNA pathway is required for the piRNA-mediated transcriptional
      silencing of TEs in this tissue. Global miRNA depletion, caused by tissue- and
      stage-specific knock down of drosha (involved in miRNA biogenesis), AGO1 or gawky
      (both responsible for miRNA activity), resulted in loss of TE-derived piRNAs and
      chromatin-mediated transcriptional de-silencing of TEs. This specific TE de
      repression was also observed upon individual titration (by expression of the
      complementary miRNA sponge) of two miRNAs (miR-14 and miR-34) as well as in a miR
      14 loss-of-function mutant background. Interestingly, the miRNA defects
      differentially affected TE- and 3' UTR-derived piRNAs. To our knowledge, this is
      the first indication of possible differences in the biogenesis or stability of TE
      and 3' UTR-derived piRNAs. This work is one of the examples of detectable
      phenotypes caused by loss of individual miRNAs in Drosophila and the first
      genetic evidence that miRNAs have a role in the maintenance of genome stability
      via piRNA-mediated TE repression. 

PMID- 25993107
TI  - Inflammasome priming is similar for francisella species that differentially
      induce inflammasome activation.
AB  - Inflammasome activation is a two-step process where step one, priming, prepares
      the inflammasome for its subsequent activation, by step two. Classically step one
      can be induced by LPS priming followed by step two, high dose ATP. Furthermore,
      when IL-18 processing is used as the inflammasome readout, priming occurs before
      new protein synthesis. In this context, how intracellular pathogens such as
      Francisella activate the inflammasome is incompletely understood, particularly
      regarding the relative importance of priming versus activation steps. To better
      understand these events we compared Francisella strains that differ in virulence
      and ability to induce inflammasome activation for their relative effects on step
      one vs. step two. When using the rapid priming model, i.e., 30 min priming by
      live or heat killed Francisella strains (step 1), followed by ATP (step 2), we
      found no difference in IL-18 release, p20 caspase-1 release and ASC
      oligomerization between Francisella strains (F. novicida, F. holarctica -LVS and
      F. tularensis Schu S4). This priming is fast, independent of bacteria viability,
      internalization and phagosome escape, but requires TLR2-mediated ERK
      phosphorylation. In contrast to their efficient priming capacity, Francisella
      strains LVS and Schu S4 were impaired in inflammasome triggering compared to F.
      novicida. Thus, observed differences in inflammasome activation by F. novicida,
      LVS and Schu S4 depend not on differences in priming but rather on their
      propensity to trigger the primed inflammasome. 

PMID- 25993108
TI  - Preparation and biodistribution of 1-((2-methoxyphenyl)
      piperazine)ferrocenecarboxamide labeled with technetium-99m as a potential brain
      receptor imaging agent.
AB  - The goal of this study is to develop a novel brain receptor imaging agent. This
      study reports the synthesis, characterization and the biological evaluation of 1
      ((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99 m
      ((99m)Tc-MP). The (99m)Tc-MP was obtained quickly (radiolabelling time < 5 min),
      in 90% yield. The (99m)Tc-complex, characterized by HPLC (20-50% ACN of 0 at 5
      min then 50% ACN of 5 at 17 min to finally with 50 at 20% ACN of 17 at 20 min),
      is stable, neutral and lipophilic enough to cross the blood-brain barrier which
      was confirmed by octanol/water partition coefficient (LogP = 1.82). In vivo
      biodistribution indicated that this complex had exceptional brain uptake (2.47%
      ID/g at 5 min and 0.75% ID/g at 60 min). The distribution of the activity at 15
      min post-injection in various rat brain regions showed a higher accumulation in
      the hippocampus area. After blocking with 8-hydroxy-2-(dipropylamino) tetralin,
      the uptake of hippocampus was decreased significantly from 0.87% ID/g to 0.21%
      ID/g at 15 min p.i., while the cerebellum had no significant decrease. The new
      (99m)Tc-cyclopentadienyltricarbonyl technetium complex reported here showed
      promising biological results, making it an interesting starting point for the
      development of a new (99m)Tc-complex as brain receptor imaging agent. 

PMID- 25993109
TI  - Molecular Typing of Pathogenic Leptospira Serogroup Icterohaemorrhagiae Strains
      Circulating in China during the Past 50 Years.
AB  - BACKGROUND: Leptospirosis is one of the most important neglected tropical
      infectious diseases worldwide. Icterohaemorrhagiae has been throughout recent
      history, and still is, the predominant serogroup of this pathogen in China.
      However, very little in detail is known about the serovars or genotypes of this
      serogroup. METHODOLOGY/PRINCIPAL FINDINGS: In this study, 120 epidemic strains
      from five geographically diverse regions in China collected over a 50 year period
      (1958~2008), and 8 international reference strains characterized by 16S rRNA
      sequencing and MLST analysis. 115, 11 and 2 strains were identified as L.
      interrogans, L. borgpetersenii, and L. kirschneri, respectively. 17 different STs
      were identified including 69 ST1 strains, 18 ST17, 18 ST128, 9 ST143 and 2 ST209.
      The remaining 12 strains belonged to 12 different STs. eBURST analysis
      demonstrated that, among the clonal complexes isolated (CCs), CC1 accounted for
      73.3% (88/120) strains representing three STs: ST1, ST128 and ST98. ST1 was the
      most likely ancestral strain of this CC, followed by singleton CC17 (17/120) and
      CC143 (11/120). Further analysis of adding 116 serogroup Icterohaemorrhagiae
      strains in the MLST database and studies previously described using global eBURST
      analysis and MST dendrogram revealed relatively similar ST clustering patterns
      with five main CCs and 8 singletons among these 244 strains. CC17 was found to be
      the most prevalent clone of pathogenic Leptospira circulating worldwide. This is
      the first time, to our knowledge, that ST1 and ST17 strains were distributed
      among 4 distinct serovars, indicating a highly complicated relationship between
      serovars and STs. CONCLUSIONS/SIGNIFICANCE: Our studies demonstrated a high level
      of genetic diversity in the serogroup Icterohaemorrhagiae strains. Distinct from
      ST17 or ST37 circulating elsewhere, ST1 included in CC1, has over the past 50
      years or so, proven to be the most prevalent ST of pathogenic leptospires
      isolated in China. Moreover, the complicated relationship between STs and
      serovars indicates an urgent need to develop an improved scheme for Leptospira
      serotyping.

PMID- 25993110
TI  - Identifying elements of patient-centered care in underserved populations: a
      qualitative study of patient perspectives.
AB  - Patient-centered care is an important goal in the delivery of healthcare.
      However, many patients do not engage in preventive medical care. In this pilot
      study, we conducted twenty in depth, semi-structured qualitative interviews at
      the University of Illinois at Chicago Health Sciences campus in a four month time
      frame. Many patients were underserved and underinsured, and we wanted to
      understand their experiences in the healthcare system. Using content analysis,
      several themes emerged from the interview data. Participants discussed the need
      for empathy and rapport with their providers. They identified provider behaviors
      that fostered a positive clinical relationship, including step-by step
      explanations of procedures, attention to body language and clinic atmosphere, and
      appropriate time management. Participants identified cost as the most common
      barrier to engaging in preventive care and discussed children and social support
      as motivating factors. A long-term relationship with a provider was an important
      motivator for preventive care, suggesting that the therapeutic alliance was
      essential to many patients. Conversely, many participants discussed a sense of
      dehumanization in the healthcare system, reporting that their life circumstances
      were overlooked, or that they were judged based on insurance status or ethnicity.
      We discuss implications for provider training and healthcare delivery, including
      the importance of patient-centered medical homes. 

PMID- 25993111
TI  - Knowledge, Attitudes, and Practices (KAP) Relating to Avian Influenza (H10N8)
      among Farmers' Markets Workers in Nanchang, China.
AB  - Three cases of avian influenza virus H10N8 were reported in Nanchang, China, as
      of April 2014. To identify the knowledge, attitudes, and practices (KAP) related
      to H10N8 among farmers' market workers, a cross-sectional survey was conducted in
      63 farmers' markets in Nanchang. Using the resulting data, characteristics of
      poultry and non-poultry workers' knowledge, attitudes, and practice were
      described. Results suggest that interventions targeting high-risk workers should
      be developed and implemented by public health agencies to prevent the spread of
      H10N8. Additionally policies that encourage farmers' market workers to receive
      influenza vaccine should be developed, adopted, and enforced. 

PMID- 25993112
TI  - Low intensity repetitive transcranial magnetic stimulation does not induce cell
      survival or regeneration in a mouse optic nerve crush model.
AB  - Low intensity repetitive Transcranial Magnetic Stimulation (LI-rTMS), a non
      invasive form of brain stimulation, has been shown to induce structural and
      functional brain plasticity, including short distance axonal sprouting. However,
      the potential for LI-rTMS to promote axonal regeneration following neurotrauma
      has not been investigated. This study examined the effect of LI-rTMS on retinal
      ganglion cell (RGC) survival, axon regeneration and levels of BDNF in an optic
      nerve crush neurotrauma model. Adult C57Bl/6J mice received a unilateral
      intraorbital optic nerve crush. Mice received 10 minutes of sham (handling
      control without stimulation) (n=6) or LI-rTMS (n = 8) daily stimulation for 14
      days to the operated eye. Immunohistochemistry was used to assess RGC survival
      (beta-3 Tubulin) and axon regeneration across the injury (GAP43). Additionally,
      BDNF expression was quantified in a separate cohort by ELISA in the retina and
      optic nerve of injured (optic nerve crush) (sham n = 5, LI-rTMS n = 5) and non
      injured mice (sham n = 5, LI-rTMS n = 5) that received daily stimulation as above
      for 7 days. Following 14 days of LI-rTMS there was no significant difference in
      mean RGC survival between sham and treated animals (p>0.05). Also, neither sham
      nor LI-rTMS animals showed GAP43 positive labelling in the optic nerve,
      indicating that regeneration did not occur. At 1 week, there was no significant
      difference in BDNF levels in the retina or optic nerves between sham and LI-rTMS
      in injured or non-injured mice (p>0.05). Although LI-rTMS has been shown to
      induce structural and molecular plasticity in the visual system and cerebellum,
      our results suggest LI-rTMS does not induce neuroprotection or regeneration
      following a complete optic nerve crush. These results help define the therapeutic
      capacity and limitations of LI-rTMS in the treatment of neurotrauma. 

PMID- 25993113
TI  - Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome
      Type II.
AB  - Crigler-Najjar Syndrome type II (CNS-II) is an autosomal recessive hereditary
      condition of unconjugated hyperbilirubinemia without hemolysis, with bilirubin
      levels ranging from 102.6 MUmol/L to 342 MUmol/L. CNS-II is caused by a
      deficiency of UDP-glucuronyl transferase (UGT), which is encoded by the UDP
      glucuronyl transferase 1A1 gene (UGT1A1). In East Asian populations, the compound
      homozygous UGT1A1 G71R and Y486D variants are frequently observed in cases with
      bilirubin levels exceeding 200 MUmol/L. In this study, we investigated the
      spectrum of UGT1A1 variations in Chinese CNS-II patients. We sequenced the
      enhancer, promoter, and coding regions of UGT1A1 in 11 unrelated Chinese CNS-II
      patients and 80 healthy controls. Nine of these patients carried variations that
      are here reported for the first time in CNS-II patients, although they have been
      previously reported for other types of hereditary unconjugated
      hyperbilirubinemia. These individual variations have less influence on UGT
      activity than do the compound homozygous variation (combination of homozygous
      G71R variant and Y486D variant). Therefore, we propose that the spectrum of
      UGT1A1 variations in CNS-II differs according to the bilirubin levels. 

PMID- 25993114
TI  - A terpenoid phytoalexin plays a role in basal defense of Nicotiana benthamiana
      against Potato virus X.
AB  - Terpenoid phytoalexins function as defense compound against a broad spectrum of
      pathogens and pests in the plant kingdom. However, the role of phytoalexin in
      antiviral defense is still elusive. In this study, we identified the biosynthesis
      pathway of a sesquiterpenoid phytoalexin, capsidiol 3-acetate as an antiviral
      response against RNA virus Potato Virus X (PVX) in Nicotiana benthamiana. NbTPS1
      and NbEAH genes were found strongly induced by PVX-infection. Enzymatic activity
      and genetic evidence indicated that both genes were involved in the PVX-induced
      biosynthesis of capsidiol 3-acetate. NbTPS1- or NbEAH-silenced plant was more
      susceptible to PVX. The accumulation of capsidiol 3-acetate in PVX-infected plant
      was partially regulated by jasmonic acid signaling receptor COI1. These findings
      provide an insight into a novel mechanism of how plant uses the basal arsenal
      machinery to mount a fight against virus attack even in susceptible species. 

PMID- 25993115
TI  - Genetic Deletion of the Transcriptional Repressor NFIL3 Enhances Axon Growth In
      Vitro but Not Axonal Repair In Vivo.
AB  - Axonal regeneration after injury requires the coordinated expression of genes in
      injured neurons. We previously showed that either reducing expression or blocking
      function of the transcriptional repressor NFIL3 activates transcription of
      regeneration-associated genes Arg1 and Gap43 and strongly promotes axon outgrowth
      in vitro. Here we tested whether genetic deletion or dominant-negative inhibition
      of NFIL3 could promote axon regeneration and functional recovery after peripheral
      nerve lesion in vivo. Contrary to our expectations, we observed no changes in the
      expression of regeneration-associated genes and a significant delay in functional
      recovery following genetic deletion of Nfil3. When NFIL3 function was inhibited
      specifically in dorsal root ganglia prior to sciatic nerve injury, we observed a
      decrease in regenerative axon growth into the distal nerve segment rather than an
      increase. Finally, we show that deletion of Nfil3 changes sciatic nerve lesion
      induced expression in dorsal root ganglia of genes that are not typically
      involved in regeneration, including several olfactory receptors and developmental
      transcription factors. Together our findings show that removal of NFIL3 in vivo
      does not recapitulate the regeneration-promoting effects that were previously
      observed in vitro, indicating that in vivo transcriptional control of
      regeneration is probably more complex and more robust against perturbation than
      in vitro data may suggest. 

PMID- 25993116
TI  - Strong Energy-Transfer-Induced Enhancement of Luminescence Efficiency of Eu(2+)-
      and Mn(2+)-Codoped Gamma-AlON for Near-UV-LED-Pumped Solid State Lighting.
AB  - A series of Eu(2+)- and Mn(2+)-codoped gamma-AlON (Al1.7O2.1N0.3) phosphors was
      synthesized at 1800  degrees C under 0.5 MPa N2 by using the gas-pressure
      sintering method (GPS). Eu(2+) and Mn(2+) ions were proved to enter into gamma
      AlON host lattice by means of XRD, CL, and EDS measurements. Under 365 nm
      excitation, two emission peaks located at 472 and 517 nm, resulting from
      4f(6)5d(1) -> 4f(7) and (4)T1(4G) -> (6)A1 electron transitions of Eu(2+) and
      Mn(2+), respectively, can be observed. Energy transfer from Eu(2+) to Mn(2+) was
      evidenced by directly observing appreciable overlap between the excitation
      spectrum of Mn(2+) and the emission spectrum of Eu(2+) as well as by the
      decreased decay time of Eu(2+) with increasing Mn(2+) concentration. The critical
      energy-transfer distance between Eu(2+) and Mn(2+) and the energy-transfer
      efficiency were also calculated. The mechanism of energy transfer was identified
      as a resonant type via a dipole-dipole mechanism. The external quantum efficiency
      was increased 7 times (from 7% for gamma-AlON:Mn(2+) to 49% for gamma
      AlON:Mn(2+),Eu(2+) under 365 nm excitation), and color-tunable emissions from
      blue-green to green-yellow were also realized with the Eu(2+) -> Mn(2+) energy
      transfer in gamma-AlON. 

PMID- 25993117
TI  - Neural differentiation modulates the vertebrate brain specific splicing program.
AB  - Alternative splicing patterns are known to vary between tissues but these
      patterns have been found to be predominantly peculiar to one species or another,
      implying only a limited function in fundamental neural biology. Here we used high
      throughput RT-PCR to monitor the expression pattern of all the annotated simple
      alternative splicing events (ASEs) in the Reference Sequence Database, in
      different mouse tissues and identified 93 brain-specific events that shift from
      one isoform to another (switch-like) between brain and other tissues. Consistent
      with an important function, regulation of a core set of 9 conserved switch-like
      ASEs is highly conserved, as they have the same pattern of tissue-specific
      splicing in all vertebrates tested: human, mouse and zebrafish. Several of these
      ASEs are embedded within genes that encode proteins associated with the neuronal
      microtubule network, and show a dramatic and concerted shift within a short time
      window of human neural stem cell differentiation. Similarly these exons are
      dynamically regulated in zebrafish development. These data demonstrate that
      although alternative splicing patterns often vary between species, there is
      nonetheless a core set of vertebrate brain-specific ASEs that are conserved
      between species and associated with neural differentiation. 

PMID- 25993118
TI  - Psychiatric and cardiovascular comorbidities as causes of long-term work
      disability among individuals with recent-onset rheumatoid arthritis: comments on
      the article by Kerola et al.

PMID- 25993119
TI  - Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb,
      Anifrolumab, in Adult Patients with Systemic Sclerosis.
AB  - Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc).
      Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor
      antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the
      downstream effects of anifrolumab and elucidate the role of type I IFN in SSc.
      Serum proteins and extracellular matrix (ECM) markers were measured in relation
      to IFN pathway activation status and SSc disease activity. Our results
      demonstrated a robust overexpression of multiple serum proteins in SSc patients,
      particularly those with an elevated baseline type I IFN gene signature.
      Anifrolumab administration was associated with significant downregulation of T
      cell-associated proteins and upregulation of type III collagen degradation
      marker. Whole-blood and skin microarray results also indicated the inhibition of
      T cell receptor and ECM-related transcripts by anifrolumab. In summary, our study
      demonstrates suppressive effects of anifrolumab on T cell activation and collagen
      accumulation through which tissue fibrosis may be reduced in SSc patients. The
      relationship between these peripheral markers and the clinical response to
      anifrolumab may be examined in larger double-blind, placebo-controlled trials. 

PMID- 25993120
TI  - A new methodology of spatial cross-correlation analysis.
AB  - Spatial correlation modeling comprises both spatial autocorrelation and spatial
      cross-correlation processes. The spatial autocorrelation theory has been well
      developed. It is necessary to advance the method of spatial cross-correlation
      analysis to supplement the autocorrelation analysis. This paper presents a set of
      models and analytical procedures for spatial cross-correlation analysis. By
      analogy with Moran's index newly expressed in a spatial quadratic form, a
      theoretical framework is derived for geographical cross-correlation modeling.
      First, two sets of spatial cross-correlation coefficients are defined, including
      a global spatial cross-correlation coefficient and local spatial cross
      correlation coefficients. Second, a pair of scatterplots of spatial cross
      correlation is proposed, and the plots can be used to visually reveal the
      causality behind spatial systems. Based on the global cross-correlation
      coefficient, Pearson's correlation coefficient can be decomposed into two parts:
      direct correlation (partial correlation) and indirect correlation (spatial cross
      correlation). As an example, the methodology is applied to the relationships
      between China's urbanization and economic development to illustrate how to model
      spatial cross-correlation phenomena. This study is an introduction to developing
      the theory of spatial cross-correlation, and future geographical spatial analysis
      might benefit from these models and indexes. 

PMID- 25993121
TI  - Measurement of larval activity in the Drosophila activity monitor.
AB  - Drosophila larvae are used in many behavioral studies, yet a simple device for
      measuring basic parameters of larval activity has not been available. This
      protocol repurposes an instrument often used to measure adult activity, the
      TriKinetics Drosophila activity monitor (MB5 Multi-Beam Activity Monitor) to
      study larval activity. The instrument can monitor the movements of animals in 16
      individual 8 cm glass assay tubes, using 17 infrared detection beams per tube.
      Logging software automatically saves data to a computer, recording parameters
      such as number of moves, times sensors were triggered, and animals' positions
      within the tubes. The data can then be analyzed to represent overall locomotion
      and/or position preference as well as other measurements. All data are easily
      accessible and compatible with basic graphing and data manipulation software.
      This protocol will discuss how to use the apparatus, how to operate the software
      and how to run a larval activity assay from start to finish. 

PMID- 25993123
TI  - Ophthalmoplegia Due to Scrub Typhus.
AB  - Scrub typhus is an acute febrile infectious disease caused by Orientia
      tsutsugamushi. The illness is usually characterized by fever, rash, and
      lymphadenopathy, but severe cases progress to pulmonary and neurological
      involvement. We report a 69-year-old man who developed ptosis and ophthalmoplegia
      with a focal nodular lesion in the anterior cavernous sinus detected with
      magnetic resonance imaging. Found to have scrub typhus, the ptosis and
      ophthalmoplegia resolved after treatment with doxycycline. 

PMID- 25993122
TI  - Lambert-Eaton Myasthenic Syndrome: Ocular Signs and Symptoms.
AB  - BACKGROUND: To evaluate ocular signs and symptoms in Lambert-Eaton myasthenic
      syndrome (LEMS) and determine the frequency of ophthalmic involvement. METHODS: A
      retrospective review of the medical records of all patients diagnosed with LEMS
      at the Mayo Clinic in Rochester, MN, from January, 1976, to December, 2010, was
      performed with special attention to ophthalmic symptoms and signs. RESULTS: One
      hundred seventy-six patients met the inclusion criteria. Ophthalmic symptoms
      included ptosis in 41 (23%), diplopia in 36 (20.5%), decreased vision in 24
      (14%), and dry eye complaints in 12 (7%). Ophthalmic signs included ptosis in 45
      (26%), abnormal ocular motility in 15 (8.5%), strabismus in 14 (8%), pupillary
      dysfunction in 12 (7%), and findings consistent with dry eyes in 4 (2%).
      CONCLUSIONS: A significant number of patients reported ophthalmic symptoms, and
      many had objective findings on clinical examination consistent with these
      symptoms. To our knowledge, this is the largest case series of ophthalmic
      findings in patients with LEMS and indicates that these patients warrant a
      complete ophthalmic examination.

PMID- 25993124
TI  - Indirect genetic effects and the dynamics of social interactions.
AB  - BACKGROUND: Indirect genetic effects (IGEs) occur when genes expressed in one
      individual alter the expression of traits in social partners. Previous studies
      focused on the evolutionary consequences and evolutionary dynamics of IGEs, using
      equilibrium solutions to predict phenotypes in subsequent generations. However,
      whether or not such steady states may be reached may depend on the dynamics of
      interactions themselves. RESULTS: In our study, we focus on the dynamics of
      social interactions and indirect genetic effects and investigate how they modify
      phenotypes over time. Unlike previous IGE studies, we do not analyse evolutionary
      dynamics; rather we consider within-individual phenotypic changes, also referred
      to as phenotypic plasticity. We analyse iterative interactions, when individuals
      interact in a series of discontinuous events, and investigate the stability of
      steady state solutions and the dependence on model parameters, such as population
      size, strength, and the nature of interactions. We show that for interactions
      where a feedback loop occurs, the possible parameter space of interaction
      strength is fairly limited, affecting the evolutionary consequences of IGEs. We
      discuss the implications of our results for current IGE model predictions and
      their limitations.

PMID- 25993125
TI  - The Evolving Role of Computed Tomographic Angiography for Lower Gastrointestinal
      Hemorrhage.

PMID- 25993126
TI  - Emergent rogue wave structures and statistics in spontaneous modulation
      instability.
AB  - The nonlinear Schrodinger equation (NLSE) is a seminal equation of nonlinear
      physics describing wave packet evolution in weakly-nonlinear dispersive media.
      The NLSE is especially important in understanding how high amplitude "rogue
      waves" emerge from noise through the process of modulation instability (MI)
      whereby a perturbation on an initial plane wave can evolve into strongly
      localised "breather" or "soliton on finite background (SFB)" structures. Although
      there has been much study of such structures excited under controlled conditions,
      there remains the open question of how closely the analytic solutions of the NLSE
      actually model localised structures emerging in noise-seeded MI. We address this
      question here using numerical simulations to compare the properties of a large
      ensemble of emergent peaks in noise-seeded MI with the known analytic solutions
      of the NLSE. Our results show that both elementary breather and higher-order SFB
      structures are observed in chaotic MI, with the characteristics of the noise
      induced peaks clustering closely around analytic NLSE predictions. A significant
      conclusion of our work is to suggest that the widely-held view that the Peregrine
      soliton forms a rogue wave prototype must be revisited. Rather, we confirm
      earlier suggestions that NLSE rogue waves are most appropriately identified as
      collisions between elementary SFB solutions. 

PMID- 25993127
TI  - Optimisation of the Photonic Efficiency of TiO2 Decorated on MWCNTs for Methylene
      Blue Photodegradation.
AB  - MWCNTs/TiO2 nanocomposite was prepared by oxidising MWCNT in H2SO4/HNO3 then
      decorating it with TiO2-p25 nanopowder. The composites were characterised using
      XRD, TEM, FT-IR PL and UV-vis spectroscopy. The TEM images have shown TiO2
      nanoparticles immobilised onto the sidewalls of the MWCNTs. The UV-vis spectrum
      confirms that the nanocomposites can significantly absorb more light in the
      visible regions compared with the commercial TiO2 (P25). The catalytic activity
      of these nanocomposites was determined by photooxidation of MB aqueous solution
      in the presence of visible light. The MWCNTs/TiO2 (1:3) mass ratio showed maximum
      degradation efficiency. However, its activity was more favourable in alkaline and
      a neutral pH than an acidic medium. 

PMID- 25993129
TI  - Quantifying the displacement of mismatches in multiple sequence alignment
      benchmarks.
AB  - Multiple Sequence Alignment (MSA) methods are typically benchmarked on sets of
      reference alignments. The quality of the alignment can then be represented by the
      sum-of-pairs (SP) or column (CS) scores, which measure the agreement between a
      reference and corresponding query alignment. Both the SP and CS scores treat
      mismatches between a query and reference alignment as equally bad, and do not
      take the separation into account between two amino acids in the query alignment,
      that should have been matched according to the reference alignment. This is
      significant since the magnitude of alignment shifts is often of relevance in
      biological analyses, including homology modeling and MSA refinement/manual
      alignment editing. In this study we develop a new alignment benchmark scoring
      scheme, SPdist, that takes the degree of discordance of mismatches into account
      by measuring the sequence distance between mismatched residue pairs in the query
      alignment. Using this new score along with the standard SP score, we investigate
      the discriminatory behavior of the new score by assessing how well six different
      MSA methods perform with respect to BAliBASE reference alignments. The SP score
      and the SPdist score yield very similar outcomes when the reference and query
      alignments are close. However, for more divergent reference alignments the SPdist
      score is able to distinguish between methods that keep alignments approximately
      close to the reference and those exhibiting larger shifts. We observed that by
      using SPdist together with SP scoring we were able to better delineate the
      alignment quality difference between alternative MSA methods. With a case study
      we exemplify why it is important, from a biological perspective, to consider the
      separation of mismatches. The SPdist scoring scheme has been implemented in the
      VerAlign web server (http://www.ibi.vu.nl/programs/veralignwww/). The code for
      calculating SPdist score is also available upon request. 

PMID- 25993128
TI  - Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to
      Sclerotinia sclerotiorum.
AB  - The xanthophyll cycle is involved in dissipating excess light energy to protect
      the photosynthetic apparatus in a process commonly assessed from non
      photochemical quenching (NPQ) of chlorophyll fluorescence. Here, it is shown that
      the xanthophyll cycle is modulated by the necrotrophic pathogen Sclerotinia
      sclerotiorum at the early stage of infection. Incubation of Sclerotinia led to a
      localized increase in NPQ even at low light intensity. Further studies showed
      that this abnormal change in NPQ was closely correlated with a decreased pH
      caused by Sclerotinia-secreted oxalate, which might decrease the ATP synthase
      activity and lead to a deepening of thylakoid lumen acidification under
      continuous illumination. Furthermore, suppression (with dithiothreitol) or a
      defect (in the npq1-2 mutant) of violaxanthin de-epoxidase (VDE) abolished the
      Sclerotinia-induced NPQ increase. HPLC analysis showed that the Sclerotinia
      inoculated tissue accumulated substantial quantities of zeaxanthin at the expense
      of violaxanthin, with a corresponding decrease in neoxanthin content.
      Immunoassays revealed that the decrease in these xanthophyll precursors reduced
      de novo abscisic acid (ABA) biosynthesis and apparently weakened tissue defense
      responses, including ROS induction and callose deposition, resulting in enhanced
      plant susceptibility to Sclerotinia. We thus propose that Sclerotinia antagonizes
      ABA biosynthesis to suppress host defense by manipulating the xanthophyll cycle
      in early pathogenesis. These findings provide a model of how photoprotective
      metabolites integrate into the defense responses, and expand the current
      knowledge of early plant-Sclerotinia interactions at infection sites. 

PMID- 25993130
TI  - Is the Relationship between Common Mental Disorder and Adiposity Bidirectional?
      Prospective Analyses of a UK General Population-Based Study.
AB  - The direction of the association between mental health and adiposity is poorly
      understood. Our objective was to empirically examine this link in a UK study.
      This is a prospective cohort study of 3 388 people (men) aged >= 18 years at
      study induction who participated in both the UK Health and Lifestyle Survey at
      baseline (HALS-1, 1984/1985) and the re-survey (HALS-2, 1991/1992). At both
      survey examinations, body mass index, waist circumference and self-reported
      common mental disorder (the 30-item General Health Questionnaire, GHQ) were
      measured. Logistic regression models were used to compute odds ratios (OR) and
      accompanying 95% confidence intervals (CI) for the associations between (1)
      baseline common mental disorder (QHQ score > 4) and subsequent general and
      abdominal obesity and (2) baseline general and abdominal obesity and re-survey
      common mental disorders. After controlling for a range of covariates,
      participants with common mental disorder at baseline experienced greater odds of
      subsequently becoming overweight (women, OR: 1.30, 1.03 - 1.64; men, 1.05, 0.81 -
      1.38) and obese (women, 1.26, 0.82 - 1.94; men, OR: 2.10, 1.23 - 3.55) than those
      who were free of common mental disorder. Similarly, having baseline common mental
      health disorder was also related to a greater risk of developing moderate (1.57,
      1.21 - 2.04) and severe (1.48, 1.09 - 2.01) abdominal obesity (women only).
      Baseline general or abdominal obesity was not associated with the risk of future
      common mental disorder. These findings of the present study suggest that the
      direction of association between common mental disorders and adiposity is from
      common mental disorder to increased future risk of adiposity as opposed to the
      converse.

PMID- 25993133
TI  - Eu(2+) luminescence in strontium aluminates.
AB  - The luminescence properties of Eu(2+) doped strontium aluminates are reported and
      reviewed for a variety of aluminates, viz. SrAl12O19, SrAl4O7, Sr4Al14O25,
      SrAl2O4 and Sr3Al2O6. The aim of the research is to investigate the role of local
      coordination and covalency of the aluminate host lattice, related to the Sr/Al
      ratio, on the optical properties of the Eu(2+) ion. The UV and VUV excited
      luminescence spectra as well as luminescence decay curves were recorded to
      characterize the luminescence properties of the investigated aluminates. The
      emission of Eu(2+) ions varies over a wide spectral range, from ultraviolet (UV)
      to red, for the series of aluminates. The variation in emission color can be
      related to the crystal-field splitting of the 5d levels and the covalent
      interaction with the surrounding oxygen anions. In the least covalent material,
      viz. SrAl12O19:Eu(2+), narrow line emission due to the (6)P7/2-(8)S7/2 transition
      occurs at 4 K, indicating that the 4f(6)5d excited state is situated above the
      (6)P7/2(4f(7)) excited state around 360 nm. The most alkaline material, viz.
      Sr3Al2O6:Eu(2+) is the most covalent host and exhibits several d-f emission bands
      in the yellow to red spectral range due to the Eu(2+) ions located on different
      crystallographic Sr(2+) sites. The Eu(2+) emission spectra in the other
      aluminates confirm the trend that with increasing Sr/Al ratio the Eu(2+) emission
      shifts to longer wavelengths. Interesting differences are observed for the Eu(2+)
      from different crystallographic sites which cannot always be related with
      apparent differences in the first oxygen coordination sphere. The discussion
      gives insight into how in a similar class of materials, strontium aluminates, the
      emission color of Eu(2+) can be tuned over a wide spectral region. 

PMID- 25993131
TI  - Three Huntington's Disease Specific Mutation-Carrying Human Embryonic Stem Cell
      Lines Have Stable Number of CAG Repeats upon In Vitro Differentiation into
      Cardiomyocytes.
AB  - Huntington disease (HD; OMIM 143100), a progressive neurodegenerative disorder,
      is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene.
      Cardiovascular symptoms, often present in early stage HD patients, are, in
      general, ascribed to dysautonomia. However, cardio-specific expression of polyQ
      peptides caused pathological response in murine models, suggesting the presence
      of a nervous system-independent heart phenotype in HD patients. A positive
      correlation between the CAG repeat size and severity of symptoms observed in HD
      patients has also been observed in in vitro HD cellular models. Here, we test the
      suitability of human embryonic stem cell (hESC) lines carrying HD-specific
      mutation as in vitro models for understanding molecular mechanisms of cardiac
      pathology seen in HD patients. We have differentiated three HD-hESC lines into
      cardiomyocytes and investigated CAG stability up to 60 days after starting
      differentiation. To assess CAG stability in other tissues, the lines were also
      subjected to in vivo differentiation into teratomas for 10 weeks. Neither
      directed differentiation into cardiomyocytes in vitro nor in vivo differentiation
      into teratomas, rich in immature neuronal tissue, led to an increase in the
      number of CAG repeats. Although the CAG stability might be cell line-dependent,
      induced pluripotent stem cells generated from patients with larger numbers of CAG
      repeats could have an advantage as a research tool for understanding cardiac
      symptoms of HD patients. 

PMID- 25993132
TI  - An Improved Method for P2X7R Antagonist Screening.
AB  - ATP physiologically activates the P2X7 receptor (P2X7R), a member of the P2X
      ionotropic receptor family. When activated by high concentrations of ATP (i.e.,
      at inflammation sites), this receptor is capable of forming a pore that allows
      molecules of up to 900 Da to pass through. This receptor is upregulated in
      several diseases, particularly leukemia, rheumatoid arthritis and Alzheimer's
      disease. A selective antagonist of this receptor could be useful in the treatment
      of P2X7R activation-related diseases. In the present study, we have evaluated
      several parameters using in vitro protocols to validate a high-throughput
      screening (HTS) method to identify P2X7R antagonists. We generated dose-response
      curves to determine the EC50 value of the known agonist ATP and the ICs50 values
      for the known antagonists Brilliant Blue G (BBG) and oxidized ATP (OATP). The
      values obtained were consistent with those found in the literature (0.7 +/- 0.07
      mM, 1.3-2.6 MUM and 173-285 MUM for ATP, BBG and OATP, respectively)
      [corrected].The Z-factor, an important statistical tool that can be used to
      validate the robustness and suitability of an HTS assay, was 0.635 for PI uptake
      and 0.867 for LY uptake. No inter-operator variation was observed, and the
      results obtained using our improved method were reproducible. Our data indicate
      that our assay is suitable for the selective and reliable evaluation of P2X7
      activity in multiwell plates using spectrophotometry-based methodology. This
      method might improve the high-throughput screening of conventional chemical or
      natural product libraries for possible candidate P2X7R antagonist or agonist.

PMID- 25993134
TI  - The changing landscape of phase I trials in oncology.

PMID- 25993135
TI  - Genomics, personalized medicine, and supportive cancer care.

PMID- 25993136
TI  - Clinical research in metastatic prostate cancer: a focus on impact and value.

PMID- 25993137
TI  - The Future of Molecular Medicine: Biomarkers, BATTLEs, and Big Data.

PMID- 25993138
TI  - Towards a personalized treatment of head and neck cancer.

PMID- 25993139
TI  - Medical education: perils and progress in educating and assessing a new
      generation of learners.

PMID- 25993140
TI  - Perspectives on clinical trials for gastrointestinal malignancies.

PMID- 25993141
TI  - I will recommend a clinical trial-if I can.

PMID- 25993142
TI  - Management of older women with early-stage breast cancer.
AB  - Breast cancer is a disease of aging. The average age at diagnosis is 61, and the
      majority of deaths occur after age 65. Caring for older women with breast cancer
      is a major challenge, as many have coexisting illness that can preclude optimal
      breast cancer treatment and which frequently have greater effect than the breast
      cancer itself. Older patients with cancer should be screened or have a brief
      geriatric assessment to detect potentially remediable problems not usually
      assessed by oncologists (e.g., self-care, falls, social support, nutrition).
      Older women with early-stage breast cancer should be treated initially with
      surgery unless they have an exceedingly short life expectancy. Primary endocrine
      therapy should be considered for patients who have hormone receptor-positive
      tumors and a very short life expectancy, an acute illness that delays surgery, or
      tumors that need to be downstaged to be resectable. Sentinel node biopsy should
      be considered for patients in whom it might affect treatment decisions. Breast
      irradiation after breast-conserving surgery may be omitted for selected older
      women, especially for those with hormone receptor-positive early-stage breast
      cancer that are compliant with adjuvant endocrine therapy. The majority of older
      women with stage I and II breast cancer have hormone receptor-positive, HER2
      negative tumors, and endocrine therapy provides them with optimal systemic
      treatment. If these patients have life expectancies exceeding at least 5 years,
      they should be considered for genetic assays to determine the potential value of
      chemotherapy. Partnering care with geriatricians or primary care physicians
      trained in geriatrics should be considered for all vulnerable and frail older
      patients. 

PMID- 25993143
TI  - Early detection of cancer: past, present, and future.
AB  - Screening in both healthy and high-risk populations offers the opportunity to
      detect cancer early and with an increased opportunity for treatment and curative
      intent. Currently, a defined role for screening exists in some cancer types, but
      each screening test has limitations, and improved screening methods are urgently
      needed. Unfortunately, many cancers still lack effective screening
      recommendations, or in some cases, the benefits from screening are marginal when
      weighed against the potential for harm. Here we review the current status of
      cancer screening: we examine the role of traditional tumor biomarkers, describe
      recommended imaging for early tumor surveillance, and explore the potential of
      promising novel cancer markers such as circulating tumor cells (CTC) and
      circulating tumor DNA. Consistent challenges for all of these screening tests
      include limited sensitivity and specificity. The risk for overdiagnosis remains a
      particular concern in screening, whereby lesions of no clinical consequence may
      be detected and thus create difficult management decisions for the clinician and
      patient. If treatment is pursued following overdiagnosis, patients may be exposed
      to morbidity from a treatment that may not provide any true benefit. The cost
      effectiveness of screening tests also needs to be an ongoing focus. The
      improvement of genomic and surveillance technologies, which leads to more precise
      imaging and the ability to characterize blood-based tumor markers of greater
      specificity, offers opportunities for major progress in cancer screening. 

PMID- 25993144
TI  - Targeted and immunotherapeutic approaches in brain metastases.
AB  - Brain metastases are a common and devastating complication of cancer. The
      approach to the management of brain metastases is often multidisciplinary and
      includes surgery, whole-brain radiation therapy (WBRT), stereotactic radiosurgery
      (SRS), and systemic therapeutic agents. Until recently, systemic therapy has had
      a limited role in the management of brain metastases because of a lack of
      activity, challenges of blood-brain barrier penetration, the heterogeneous
      patient population, and a heavily pretreated patient population. Advances in the
      understanding of the biology of brain metastases and molecularly defined disease
      subsets have facilitated an emerging role of novel therapeutic agents, including
      targeted therapies and immunotherapy, in the management of brain metastases. 

PMID- 25993145
TI  - Managing immune checkpoint-blocking antibody side effects.
AB  - Immune checkpoint-blocking antibodies that enhance the immune system's ability to
      fight cancer are becoming important components of treatment for patients with a
      variety of malignancies. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) was
      the first immune checkpoint to be clinically targeted, and ipilimumab, an
      inhibitor of CTLA-4, was approved by the U.S. Food and Drug Administration (FDA)
      for patients with advanced melanoma. The programmed cell death-1 (PD-1) receptor
      and one of its ligands, PD-L1, more recently have shown great promise as
      therapeutic targets in a variety of malignancies. Nivolumab and pembrolizumab
      recently have been FDA- approved for patients with melanoma and additional
      approvals within this therapeutic class are expected. The use of anti-CTLA-4 and
      anti-PD-1/PD-L1 antibodies is associated with side effects known as immune
      related adverse events (irAEs). Immune-related adverse events affect the
      dermatologic, gastrointestinal, hepatic, endocrine, and other organ systems.
      Temporary immunosuppression with corticosteroids, tumor necrosis factor-alpha
      antagonists, mycophenolate mofetil, or other agents can be effective treatment.
      This article describes the side-effect profile of the checkpoint-blocking
      antibodies that target CTLA-4 and PD-1/PD-L1 and provides suggestions on how to
      manage specific irAEs. 

PMID- 25993146
TI  - Systemic treatment: maintenance compared with holiday.
AB  - With the currently available cytotoxic and targeted drugs, metastatic colorectal
      cancer (mCRC) may be controlled by systemic treatment for a substantial period of
      time. However, many questions remain about the optimal use of drugs and duration
      of treatment. The feasibility of chemotherapy-free intervals has been studied in
      patients with mCRC treated with chemotherapy alone, but the results are
      conflicting. Current data show that oxaliplatin may be safely interrupted, but
      they do not allow a firm conclusion on the safety of a full treatment break of
      chemotherapy. For targeted therapy, continuous inhibition of intracellular
      signaling by prolonged administration would theoretically be beneficial for
      efficacy of treatment. Recent data support the use of maintenance treatment with
      chemotherapy and bevacizumab. No data on the optimal duration of treatment with
      anti-epidermal growth factor receptor (EGFR) agents are currently available. 

PMID- 25993147
TI  - The spectrum of neuroendocrine tumors: histologic classification, unique features
      and areas of overlap.
AB  - Neuroendocrine neoplasms are diverse in terms of sites of origin, functional
      status, and degrees of aggressiveness. This review will introduce some of the
      common features of neuroendocrine neoplasms and will explore the differences in
      pathology, classification, biology, and clinical management between tumors of
      different anatomic sites, specifically, the lung, pancreas, and prostate. Despite
      sharing neuroendocrine differentiation and histologic evidence of the
      neuroendocrine phenotype in most organs, well-differentiated neuroendocrine
      tumors (WD-NETs) and poorly differentiated neuroendocrine carcinomas (PD-NECs)
      are two very different families of neoplasms. WD-NETs (grade 1 and 2) are
      relatively indolent (with a natural history that can evolve over many years or
      decades), closely resemble non-neoplastic neuroendocrine cells, and demonstrate
      production of neurosecretory proteins, such as chromogranin A. They arise in the
      lungs and throughout the gastrointestinal tract and pancreas, but WD-NETs of the
      prostate gland are uncommon. Surgical resection is the mainstay of therapy, but
      treatment of unresectable disease depends on the site of origin. In contrast, PD
      NECs (grade 3, small cell or large cell) of all sites often demonstrate
      alterations in P53 and Rb, exhibit an aggressive clinical course, and are treated
      with platinum-based chemotherapy. Only WD-NETs arise in patients with inherited
      neuroendocrine neoplasia syndromes (e.g., multiple endocrine neoplasia type 1),
      and some common genetic alterations are site-specific (e.g., TMPRSS2-ERG gene
      rearrangement in PD-NECs arising in the prostate gland). Advances in our
      understanding of the molecular basis of NETs should lead to new diagnostic and
      therapeutic strategies and is an area of active investigation. 

PMID- 25993148
TI  - New and promising strategies in the management of bladder cancer.
AB  - Bladder cancer is a complex and aggressive disease for which treatment strategies
      have had limited success. Improvements in detection, treatment, and outcomes in
      bladder cancer will require the integration of multiple new approaches, including
      genomic profiling, immunotherapeutics, and large randomized clinical trials. New
      and promising strategies are being tested in all disease states, including
      nonmuscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC),
      and metastatic urothelial carcinoma (UC). Efforts are underway to develop better
      noninvasive urine biomarkers for use in primary or secondary detection of NMIBC,
      exploiting our genomic knowledge of mutations in genes such as RAS, FGFR3,
      PIK3CA, and TP53 and methylation pathways alone or in combination. Recent data
      from a large, randomized phase III trial of adjuvant cisplatin-based chemotherapy
      add to our knowledge of the value of perioperative chemotherapy in patients with
      MIBC. Finally, bladder cancer is one of a growing list of tumor types that
      respond to immune checkpoint inhibition, opening the potential for new
      therapeutic strategies for treatment of this complex and aggressive disease. 

PMID- 25993149
TI  - Chemotherapy for Patients with BRCA1 and BRCA2-Mutated Ovarian Cancer: Same or
      Different?
AB  - Retrospective studies have shown an improved prognosis, higher response rates to
      platinum-containing regimens, and longer treatment-free intervals between
      relapses in patients with BRCA 1 and BRCA 2 (BRCA1/2)-mutated ovarian cancer
      (BMOC) compared with patients who are not carriers of this mutation. These
      features of BMOC are attributed to homologous-recombination repair (HR)
      deficiency in the absence of BRCA1/2 function, which results in an impaired
      ability of tumor cells to repair platinum-induced double-strand breaks (DSBs),
      thereby conferring increased chemosensitivity and increased sensitivity to
      poly(ADP-ribose) polymerase (PARP) enzyme inhibition and other DNA-damaging
      chemotherapeutic agents such as pegylated liposomal doxorubicin (PLD). Therefore,
      the chemotherapeutic approach for patients with BMOC should focus on treatment
      with platinum-based chemotherapy at first-line and recurrent-disease settings and
      measures to increase the platinum-free interval following early platinum
      resistant relapse (i.e., progression-free survival of less than 6 months from
      last platinum-based chemotherapy) by using nonplatinum cytotoxic agents, with the
      aim of reintroducing platinum again at a later date. The role of first-line
      intraperitoneal platinum-based therapy in the specific context of BMOC also
      merits further analysis. Other than platinum, alternative DNA-damaging agents
      (including PLD and trabectedin) also may have a therapeutic role in patients with
      recurrent BMOC. The recent approval of olaparib for clinical use in Europe and
      the United States will also affect chemotherapeutic strategies for these
      patients. Further work to clarify the precise relationship between BRCA1/2
      mutation genotype and clinical phenotype is crucial to delineating the optimal
      therapeutic choices in the future for patients with BMOC. 

PMID- 25993150
TI  - Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising
      from the mucosal epithelia in the head and neck region. The most common risk
      factors are tobacco use, alcohol consumption, and HPV infection, particularly in
      the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct
      from the HPV-negative HNSCC; however, deregulations within the
      phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive
      and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway
      with a gain-of-function in HNSCC. This article reviews the basic biology and
      clinical data from the trials involving anticancer agents targeting the PI3K
      pathway in HNSCC. It also discusses the difficulties of translating the
      preclinical data to tangible clinical efficacy of these agents in patients with
      HNSCC even when there is significant preclinical data suggesting the PI3K pathway
      is a promising therapeutic target in HNSCC. We conclude that additional studies
      to determine appropriate patient selection for the activation of PI3K pathway and
      to develop targeted agents either as a monotherapy or combination therapy with
      favorable toxicity profiles are required before a broader clinical application. 

PMID- 25993151
TI  - The impact of industry on oncology research and practice.
AB  - Public scrutiny has increased over potential conflicts of interest among oncology
      researchers and providers. Given the increased prevalence and complexity of
      industry relationships, oncologists are increasingly faced with ethical
      challenges when navigating their financial relationships with industry.
      Oncologists are continually dealing with changing conflict of interest policies
      within academic centers and professional societies. With the recent passage of
      The Sunshine Act, oncologists are beginning to understand the repercussions of
      this new law. The consequences of the increasing use of direct-to-consumer
      advertising on patients with cancer are also unclear. Finally, industry's
      perspective on the evolution of these relationships is not clearly understood.
      This manuscript discusses issues related to industry's influence on oncology
      practice and research. 

PMID- 25993152
TI  - From Philadelphia-Negative to JAK2-Positive: Effect of Genetic Discovery on Risk
      Stratification and Management.
AB  - The 2005 discovery of the JAK2 mutation redefined the diagnosis and natural
      history of myeloproliferative neoplasms (MPNs). Most importantly, this
      improvement in the pathobiologic conceptualization has focused our evolution of
      this field from being defined as what it is not (e.g., Philadelphia [Ph]
      negative) to what it is (e.g., JAK2-positive, CALR-positive) in the majority of
      MPN cases. In the ensuing 10 years, the field has experienced a paradigm shift in
      terms of understanding of the biologic basis of the development of MPNs, an
      explosion of knowledge of the genetics of MPNs, and has translated disease
      knowledge into effective targeted therapies. With greater uniformity and
      agreement on the diagnosis and differences among the individual MPNs, augmented
      by improved cytogenetic and molecular classification, attention has turned now to
      addressing the need for uniformity in risk stratification of patients in the
      clinic for both disease complications and disease transformation. This article
      will highlight the developments in the field with regard to risk stratification
      and prognostication in MPNs with focus on the clinical aspects of the patient who
      presents with either essential thrombocytosis (ET), polycythemia vera (PV), or
      myelofibrosis (MF). 

PMID- 25993153
TI  - Beyond adenocarcinoma: current treatments and future directions for squamous,
      small cell, and rare lung cancer histologies.
AB  - Lung cancer encompasses a diverse spectrum of histologic subtypes. Until
      recently, the majority of therapeutic advances were limited to the minority of
      patients with adenocarcinoma. With the advent of comprehensive genomic profiling
      of squamous and small cell lung cancers, new therapeutic targets have emerged.
      For squamous tumors, the most promising of these include fibroblast growth factor
      receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin
      domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the
      antiangiogenic agent ramucirumab was approved for all non-small cell lung cancer
      (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also
      appear to be promising for these cases. Genomic analysis of small cell lung
      cancer has revealed a high mutation burden, but relatively few druggable driver
      oncogenic alterations. Current treatment strategies under investigation are
      focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as
      immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of
      diseases that may be treated with somatostatin analogs, cytotoxic agents, and
      molecularly targeted therapies. Radiolabeled somatostatin analogs and
      combinations with mammalian target of rapamycin (mTOR) inhibitors also show
      potential. Large cell neuroendocrine tumors share numerous clinical, pathologic,
      and molecular features with small cell lung cancer; however, whether they should
      be treated similarly or according to a NSCLC paradigm remains a matter of debate.

PMID- 25993154
TI  - Management of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually
      diagnosed in asymptomatic patients with early-stage disease. The standard
      management approach is careful observation, irrespective of risk factors unless
      patients meet the International Workshop on CLL (IWCLL) criteria for "active
      disease," which requires treatment. The initial standard therapy for most
      patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or
      obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine,
      or chlorambucil) depending on multiple factors including the physical fitness of
      the patient. However, patients with very high-risk CLL because of a 17p13
      deletion (17p-) with or without mutation of TP53 (17p-/TP53mut) have poor
      responses to chemoimmunotherapy and require alternative treatment regimens
      containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling
      pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and
      idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta],
      respectively) are currently approved for the treatment of relapsed/refractory CLL
      and all patients with 17p- (ibrutinib), and in combination with rituximab for
      relapsed/refractory patients (idelalisib). These agents offer great efficacy,
      even in chemotherapy refractory CLL, with increased tolerability, safety, and
      survival. Ongoing studies aim to determine the best therapy combinations with the
      goal of achieving long-term disease control and the possibility of developing a
      curative regimen for some patients. CLL is associated with a wide range of
      infectious, autoimmune, and malignant complications. These complications result
      in considerable morbidity and mortality that can be minimized by early detection
      and aggressive management. This active monitoring requires ongoing patient
      education, provider vigilance, and a team approach to patient care. 

PMID- 25993155
TI  - Achievements and challenges of molecular targeted therapy in melanoma.
AB  - The treatment of melanoma has been revolutionized over the past decade with the
      development of effective molecular and immune targeted therapies. The great
      majority of patients with melanoma have mutations in oncogenes that predominantly
      drive signaling through the mitogen activated protein kinase (MAPK) pathway.
      Analytic tools have been developed that can effectively stratify patients into
      molecular subsets based on the identification of mutations in oncogenes and/or
      tumor suppressor genes that drive the MAPK pathway. At the same time, potent and
      selective inhibitors of mediators of the MAPK pathway such as RAF, MEK, and ERK
      have become available. The most dramatic example is the development of single
      agent inhibitors of BRAF (vemurafenib, dabrafenib, encorafenib) and MEK
      (trametinib, cobimetinib, binimetinib) for patients with metastatic BRAFV600
      mutant melanoma, a subset that represents 40% to 50% of patients with metastatic
      melanoma. More recently, the elucidation of mechanisms underlying resistance to
      single-agent BRAF inhibitor therapy led to a second generation of trials that
      demonstrated the superiority of BRAF inhibitor/MEK inhibitor combinations
      (dabrafenib/trametinib; vemurafenib/cobimetinib) compared to single-agent BRAF
      inhibitors. Moving beyond BRAFV600 targeting, a number of other molecular subsets
      -such as mutations in MEK, NRAS, and non-V600 BRAF and loss of function of the
      tumor suppressor neurofibromatosis 1 (NF1)--are predicted to respond to MAPK
      pathway targeting by single-agent pan-RAF, MEK, or ERK inhibitors. As these
      strategies are being tested in clinical trials, preclinical and early clinical
      trial data are now emerging about which combinatorial approaches might be best
      for these patients.

PMID- 25993156
TI  - Challenges to Standardizing the Care for Adult Cancer Survivors: Highlighting
      ASCO's Fatigue and Anxiety and Depression Guidelines.
AB  - There are over 14 million survivors of cancer living in the United States alone
      and tens of millions more worldwide, with this population expected to nearly
      double in the next decade. The successes of prevention, early detection, and
      better therapies have lead to an emerging understanding of the substantial
      medical and psychosocial issues for this growing population that must be tackled
      for individuals and from the health care system and societal perspectives. 

PMID- 25993158
TI  - Using social media to learn and communicate: it is not about the tweet.
AB  - Social media can be defined as the use of media to interact with social networks.
      Social media is not about the content of the tweet, inasmuch as the technologies
      and social media platforms influence how content is generated, disseminated, and
      used. Social media is not dead, but rather it offers rapid incoming and outgoing
      forms of communication, which may be utilized in a variety of "use cases" in
      medicine and oncology. 

PMID- 25993157
TI  - Approaches to reduce the long-term burden of treatment-related complications in
      survivors of childhood cancer.
AB  - Advances in diagnostics, treatment strategies, and supportive care have
      contributed to a marked improvement in outcomes for children with cancer. This
      has resulted in a growing number of long-term childhood cancer survivors.
      Currently there are over 360,000 individuals who are survivors of childhood
      cancer in the United States. However, treatment for patients with childhood
      cancer with chemotherapy, radiation, and/or hematopoietic stem cell
      transplantation can result in health-related complications that may not become
      evident until years after completion of treatment. As a result, several
      initiatives have been established to help standardize the surveillance for
      treatment-related late effects in childhood cancer survivors. This review
      highlights emerging concepts related to commonly reported late effects, such as
      subsequent malignant neoplasms, cardiovascular disease, and endocrinopathies. It
      also discusses relevant population-based screening strategies to mitigate the
      long-term health-related burden in vulnerable populations of survivors. 

PMID- 25993159
TI  - Application of molecular biology to individualize therapy for patients with
      liposarcoma.
AB  - Liposarcomas are one the most common of over 50 histologic subtypes of soft
      tissue sarcomas that are mostly resistant to chemotherapy. Histologically,
      liposarcomas themselves are heterogeneous and fall into four distinct subtypes:
      well-differentiated/atypical lipomatous tumor, dedifferentiated liposarcoma,
      myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Surgical resection
      with negative margins remains the mainstay for definitive treatment for operable
      disease. For unresectable disease, retrospective studies have identified myxoid
      (round cell) and pleomorphic sarcomas to be relatively responsive to
      chemotherapy. Recent studies have identified distinct genetic aberrations that
      not only aid in the diagnosis of particular liposarcoma subtypes, but represent
      actionable targets as they are considered central to disease pathogenesis. Cyclin
      dependent kinase 4 (CDK4) and murine double minute 2 (MDM2) are overexpressed in
      well-differentiated and dedifferentiated liposarcomas and offer tantalizing
      opportunities that are being pursued in clinical trials. Myxoid (round cell)
      liposarcomas appear to be sensitive to trabectedin, which is currently under U.S.
      Food and Drug Administration (FDA) review. Liposarcomas do not represent a
      uniform disease and understanding the underlying molecular mechanism will help
      not only in accurate diagnosis but in selecting the appropriate treatment. 

PMID- 25993160
TI  - Metabolism and oxidative stress response pathways in kidney cancer: a tale of
      chance and necessity.
AB  - Over 270,000 patients are affected with kidney cancer worldwide and 120,000 died
      from this disease in 2014. Over the last few decades, important progress has been
      made in our understanding of the genetic and molecular mechanisms underlying the
      growth of these tumors, which has led to improvement in patient care. Some of the
      most significant recent advances came from the increasing number of large
      datasets generated by bioinformatics (genomics, proteomics, etc.) and their
      integration to characterize the genetic and molecular factors responsible for
      kidney tumor development and survival. Interestingly, deregulated metabolism and
      oxidative stress pathways are commonly found in advanced-stage kidney tumors and
      are important factors to consider and potentially target when developing
      therapeutic approaches. 

PMID- 25993161
TI  - Biology and clinical management challenges in meningioma.
AB  - Meningiomas are the most frequently occurring intracranial tumors. They are
      characterized by a broad spectrum of histopathologic appearance. Molecular
      alterations driving meningioma development, which affect the NF2 gene, are found
      in roughly 50% of patients. Rare genetic events in benign meningiomas are
      mutations in TRAF7, KLF4, AKT1, and SMO; all of these mutations are exclusive of
      NF2 alterations. Progression to a clinically aggressive meningioma is linked to
      inactivation of CDKN2A/B genes, and a plethora of signaling molecules have been
      described as activated in meningiomas, which supports the concept of successful
      clinical use of specific inhibitors. Established treatments include surgical
      resection with or without radiotherapy delivered in a single fraction, a few
      large fractions (radiosurgery), or multiple fractions (fractionated
      radiotherapy). For recurrent and aggressive tumors, inhibitors of the vascular
      endothelial growth factor (VEGF) pathway, such as vatalinib, bevacizumab, and
      sunitinib, showed signs of activity in small, uncontrolled studies, and
      prospective clinical studies will test the efficacy of the tetrahydroisoquinoline
      trabectedin and of SMO and AKT1 inhibitors. 

PMID- 25993162
TI  - What Can We Learn about Antibody-Drug Conjugates from the T-DM1 Experience?
AB  - Antibody conjugates are a diverse class of therapeutics that consist of a
      cytotoxic agent linked covalently to an antibody or antibody fragment directed
      toward a specific cell surface target expressed by tumor cells. The notion that
      antibodies directed toward targets on the surface of malignant cells could be
      used for drug delivery is not new. The history of antibody conjugates has been
      marked by hurdles identified and overcome. Early conjugates used mouse
      antibodies, drugs that either were not sufficiently potent, were immunogenic
      (proteins), or were too toxic, and linkers that were not sufficiently stable in
      circulation. Four main avenues have been explored using antibodies to target
      cytotoxic agents to malignant cells: antibody-protein toxin (or antibody fragment
      protein toxin fusion) conjugates, antibody-chelated radionuclide conjugates,
      antibody-small molecule conjugates, and antibody-enzyme conjugates administered
      along with small molecule prodrugs that require metabolism by the conjugated
      enzyme to release the activated species. Technology is continuing to evolve
      regarding the protein and small molecule components, and it is likely that single
      chemical entities soon will be the norm for antibody-drug conjugates. Only
      antibody-radionuclide conjugates and antibody-drug conjugates have reached the
      regulatory approval stage, and there are more than 40 antibody conjugates in
      clinical trials. The time may have come for this technology to become a major
      contributor to improving treatment for patients with cancer. 

PMID- 25993163
TI  - Geriatric oncology and clinical trials.
AB  - The overall aging of the population has resulted in a marked increase in the
      number of older patients with cancer. These patients have specific needs that are
      different from those of the younger population. Cancer clinical trials have
      included an inadequate number of older patients, resulting in lack of meaningful
      data to make evidence-based decisions for this population. As a result,
      clinicians have to extrapolate data from younger and healthier patients. There
      are a number of reasons for this under-representation, including a design and
      implementation structure for clinical trials that does not meet the needs of this
      vulnerable population. Issues that need to be addressed include alterations in
      eligibility criteria to make them less restrictive by accounting for multiple
      comorbidities and prior malignancy and endpoints specific for older patients,
      such as quality of life, changes in function, and maintenance of independence.
      Other issues specific to the older population include alterations in dose
      limiting toxicity, measures of treatment-related toxicity, and polypharmacy.
      Phase I trials can be appropriate for older patients but need to be tailored to
      their needs. Some form of geriatric assessment needs to be included to help with
      eligibility, assessment, and stratification. For future clinical trials to be
      truly meaningful they need to appropriately assess and incorporate the needs of
      the majority of the cancer population. 

PMID- 25993164
TI  - The global conduct of cancer clinical trials: challenges and opportunities.
AB  - The nature of clinical research has changed substantially over the last 2
      decades, evolving from being centered almost exclusively in developed countries
      to a more global scenario that is increasingly involving less developed regions
      of the world. Pharmaceutical companies and some academic cooperative groups have
      been conducting challenging, large pivotal registration studies with
      multinational participation. The much more needed globalization of academic
      research demands particular attention and represents a worthwhile subject for a
      more profound discussion. The requirement of large sample sizes and the potential
      for fast recruitment leading to a speedy completion of clinical studies are
      probably the most important factors that have fueled globalization of studies.
      Reduced operational costs and the ability to expedite the regulatory approval of
      drugs in various countries or regions are also important drivers. Globalization
      of research should be seen as having a much wider effect in the societies
      involved, in particular, when we consider public health, economic, social, and
      ethical implications. Most importantly, the process of expanding the network of
      clinical research sites also fosters the integration and the development of
      closer relationships among investigators at a global level. We consider this an
      essential element that should remain a prominent element in the discussion. In
      this article, we address the underlying reasons for globalization and we
      highlight some of the scientific and ethical concerns arising as a consequence.
      Finally, some strategies to address and mitigate the challenges of conducting
      multinational clinical research are proposed. 

PMID- 25993165
TI  - Improving Clinical Trial Efficiency: Thinking outside the Box.
AB  - Clinical trial design strategies have evolved over the past few years as a means
      to accelerate the drug development process so that the right therapies can be
      delivered to the right patients. Basket, umbrella, and adaptive enrichment
      strategies represent a class of novel designs for testing targeted therapeutics
      in oncology. Umbrella trials include a central infrastructure for screening and
      identification of patients, and focus on a single tumor type or histology with
      multiple subtrials, each testing a targeted therapy within a molecularly defined
      subset. Basket trial designs offer the possibility to include multiple
      molecularly defined subpopulations, often across histology or tumor types, but
      included in one cohesive design to evaluate the targeted therapy in question.
      Adaptive enrichment designs offer the potential to enrich for patients with a
      particular molecular feature that is predictive of benefit for the test treatment
      based on accumulating evidence from the trial. This review will aim to discuss
      the fundamentals of these design strategies, the underlying statistical
      framework, the logistical barriers of implementation, and, ultimately, the
      interpretation of the trial results. New statistical approaches, extensive
      multidisciplinary collaboration, and state of the art data capture technologies
      are needed to implement these strategies in practice. Logistical challenges to
      implementation arising from centralized assay testing, requirement of multiple
      specimens, multidisciplinary collaboration, and infrastructure requirements will
      also be discussed. This review will present these concepts in the context of the
      National Cancer Institute's precision medicine initiative trials: MATCH,
      ALCHEMIST, Lung MAP, as well as other trials such as FOCUS4. 

PMID- 25993166
TI  - Overcoming Resistance to Anti-EGFR Therapy in Colorectal Cancer.
AB  - Our understanding of the genetic and nongenetic molecular alterations associated
      with anti-epidermal growth factor receptor (EGFR) therapy resistance in
      colorectal cancer (CRC) has markedly expanded in recent years. Mutations in RAS
      genes (KRAS/NRAS exons 2, 3, or 4) predict a lack of clinical benefit when anti
      EGFR monoclonal antibodies (mAbs) are added to chemotherapy. Genetic events in
      additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide
      3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA
      mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to
      cetuximab or panitumumab. Polymorphisms that block antibody binding as a result
      of EGFR extracellular domain mutations have been reported. Nongenetic mechanisms,
      including compensatory activation of receptor tyrosine kinases HER3 and MET,
      together with high expression of the ligands amphiregulin, transforming growth
      factor alpha heregulin, and hepatocyte growth factor in the tumor
      microenvironment also are thought to be involved in resistance. In one-third of
      the samples, more than one genetic event can be found, and nongenetic events most
      likely coexist with gene alterations. Furthermore, activation of a gene
      expression signature of epithelial-mesenchymal transition has been associated
      with reduced cellular dependence on EGFR signaling. Collectively, this body of
      work provides convincing evidence that the molecular heterogeneity of CRC plays
      an important role in the context of resistance to anti-EGFR therapy. Herein, we
      discuss how this knowledge has been translated into drug development strategies
      to overcome primary and acquired anti-EGFR resistance, with rational combinations
      of targeted agents in genomically selected populations, second-generation EGFR
      inhibitors, and other agents expected to boost the immune response at the tumor
      site. 

PMID- 25993167
TI  - Resistance to Anti-HER2 Therapies in Breast Cancer.
AB  - HER2 is amplified or overexpressed in 20% to 25% of breast cancers. HER2 is a
      redundant, robust, and powerful signaling pathway that represents an attractive
      therapeutic target. Anti-HER2 therapy in the clinic has resulted in significant
      improvements in patient outcomes and, in recent years, combinations of anti-HER2
      therapies have been explored and carry great promise. However, treatment
      resistance remains a problem. Resistance can be mediated, among others, by
      pathway redundancy, reactivation, or the utilization of escape pathways.
      Understanding mechanisms of resistance can lead to better therapeutic strategies
      to overcome resistance and optimize outcomes. 

PMID- 25993169
TI  - Neoadjuvant therapy for breast cancer: controversies in clinical trial design and
      standard of care.
AB  - Neoadjuvant therapy for breast cancer has been increasingly used in recent years
      as first-line treatment for operable breast cancer-serving as both a management
      strategy and a research tool. In addition to the established clinical benefits of
      down-staging more locally advanced cancers and improving breast-conservation
      rates, investigators have recognized the potential advantages of this approach in
      developing new therapies. Preoperative systemic therapy provides the opportunity
      for in vivo assessment of pharmacodynamic markers to assess biologic effects and
      allows new compounds to be tested in a more responsive, treatment-naive
      population. In addition, early surrogates of response, such as pathologic
      complete response (pCR) and residual cancer burden, provide proximate measures
      that correlate with long-term outcomes, thus potentially shortening the time
      needed to identify effective adjuvant therapies. Despite the advantages of
      neoadjuvant therapy for research and clinical practice, its use is characterized
      by persistent controversy and healthy debate regarding how to optimally use
      research findings and when to integrate them into the standard of care for daily
      management. Among the controversies surrounding neoadjuvant therapy use are
      questions about defining the best endpoint for assessing treatment efficacy,
      deciding when results from research should be used in daily clinical practice,
      and how the growing use of neoadjuvant therapy affects locoregional treatments. 

PMID- 25993168
TI  - Combating acquired resistance to tyrosine kinase inhibitors in lung cancer.
AB  - The prospective identification and therapeutic targeting of oncogenic tyrosine
      kinases with tyrosine kinase inhibitors (TKIs) has revolutionized the treatment
      for patients with non-small cell lung cancer (NSCLC). TKI therapy frequently
      induces dramatic clinical responses in molecularly defined cohorts of patients
      with lung cancer, paving the way for the implementation of precision medicine.
      Unfortunately, acquired resistance, defined as tumor progression after initial
      response, seems to be an inevitable consequence of this treatment approach. This
      brief review will provide an overview of the complex and heterogeneous problem of
      acquired resistance to TKI therapy in NSCLC, with a focus on EGFR-mutant and ALK
      rearranged NSCLC. In vitro models of TKI resistance and analysis of tumor biopsy
      samples at the time of disease progression have generated breakthroughs in our
      understanding of the spectrum of mechanisms by which a tumor can thwart TKI
      therapy and have provided an important rationale for the development of novel
      approaches to delay or overcome resistance. Numerous ongoing clinical trials
      implement strategies, including novel, more potent TKIs and rational combinations
      of targeted therapies, some of which have already proven effective in surmounting
      therapeutic resistance. 

PMID- 25993170
TI  - Clinical tumor sequencing: opportunities and challenges for precision cancer
      medicine.
AB  - Advances in tumor genome sequencing have enabled discovery of actionable
      alterations leading to novel therapies. Currently, there are approved targeted
      therapies across various tumors that can be matched to genomic alterations, such
      as point mutations, gene amplification, and translocations. Tools to detect these
      genomic alterations have emerged as a result of decreasing costs and improved
      throughput enabled by next-generation sequencing (NGS) technologies. NGS has been
      successfully utilized for developing biomarkers to assess susceptibility,
      diagnosis, prognosis, and treatment of cancers. However, clinical application
      presents some potential challenges in terms of tumor specimen acquisition,
      analysis, privacy, interpretation, and drug development in rare cancer subsets.
      Although whole-genome sequencing offers the most complete strategy for tumor
      analysis, its present utility in clinical care is limited. Consequently, targeted
      gene capture panels are more commonly employed by academic institutions and
      commercial vendors for clinical grade cancer genomic testing to assess molecular
      eligibility for matching therapies, whereas whole-exome and transcriptome
      (RNASeq) sequencing are being utilized for discovery research. This review
      discusses the strategies, clinical challenges, and opportunities associated with
      the application of cancer genomic testing for precision cancer medicine. 

PMID- 25993171
TI  - Clinical Trials of Precision Medicine through Molecular Profiling: Focus on
      Breast Cancer.
AB  - High-throughput technologies of molecular profiling in cancer, such as gene
      expression profiling and next-generation sequencing, are expanding our knowledge
      of the molecular landscapes of several cancer types. This increasing knowledge
      coupled with the development of several molecularly targeted agents hold the
      promise for personalized cancer medicine to be fully realized. Moreover, an
      expanding armamentarium of targeted agents has been approved for the treatment of
      specific molecular cancer subgroups in different diagnoses. According to this
      paradigm, treatment selection should be dictated by the specific molecular
      aberrations found in each patient's tumor. The classical clinical trials paradigm
      of patients' eligibility being based on clinicopathologic parameters is being
      abandoned, with current clinical trials enrolling patients on the basis of
      specific molecular aberrations. New, innovative trial designs have been generated
      to better tackle the multiple challenges induced by the increasing molecular
      fragmentation of cancer, namely: (1) longitudinal cohort studies with or without
      downstream trials, (2) studies assessing the clinical utility of molecular
      profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials,
      and (6) adaptive design trials. This article provides an overview of the
      challenges for clinical trials in the era of molecular profiling of cancer.
      Subsequently, innovative trial designs with respective examples and their
      potential to expedite efficient clinical development of targeted anticancer
      agents is discussed. 

PMID- 25993172
TI  - Locally advanced rectal cancer: time for precision therapeutics.
AB  - The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a
      landmark trial demonstrating the benefit of adding pelvic radiation to the
      treatment regimen for locally advanced rectal cancer with a resultant decrease in
      local recurrence from 25% to 16%. These results ushered in the era of multimodal
      therapy for rectal cancer, heralding modern treatment and changing the standard
      of care in the United States. We have seen many advances over the past 3 decades,
      including optimization of the administration and timing of radiation, widespread
      adoption of total mesorectal excision (TME), and the implementation of more
      effective systemic chemotherapy. The current standard is neoadjuvant
      chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and
      adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen
      have been impressive, with a reported local recurrence rate of less than 10%.
      However, the rates of distant relapse remain 30% to 40%, indicating room for
      improvement. In addition, trimodality therapy is arduous and many patients are
      unable to complete the full course of treatment. In this article we discuss the
      current standard of care and alternative strategies that have evolved in an
      attempt to individualize therapy according to risk of recurrence. 

PMID- 25993173
TI  - Biologic therapies in colorectal cancer: indications and contraindications.
AB  - The role of antiangiogenic and anti-epidermal growth factor receptor (EGFR)
      agents has been investigated extensively in colorectal cancer in the palliative,
      adjuvant, and neoadjuvant settings. Although the role of biologic agents has
      become well-defined in the first, second, and subsequent lines of treatment of
      metastatic colorectal cancer (mCRC), considerable debate continues around the
      optimal sequencing and around optimal patient selection. The benefits from
      integrating bevacizumab or cetuximab in the adjuvant setting have been
      investigated in several randomized phase III clinical trials in stage II/III
      disease, all with disappointing results. Neoadjuvant approaches incorporating
      biologic therapy in patients with liver metastatic disease have led to mixed
      results. Although the current evidence does suggest increased down-staging and
      increased resectability with the addition of cetuximab in patients with initially
      unresectable or borderline resectable liver metastases, a positive effect of anti
      EGFR therapy on the overall survival (OS) in this setting is not conclusive.
      Patients with resectable liver metastases derive no benefit and may experience
      potential harm from the addition of cetuximab to neoadjuvant chemotherapy.
      Similarly, there is neither rationale nor adequate data to support the addition
      of bevacizumab to neoadjuvant chemotherapy in patients with resectable liver
      metastases. In this review, we examine the role of antiangiogenesis and anti-EGFR
      therapies across the spectrum of adjuvant, neoadjuvant, and metastatic disease. 

PMID- 25993174
TI  - Precision medicine for metastatic breast cancer.
AB  - Genomic studies have shown that large numbers of candidate targets are observed
      in breast cancer. Nevertheless, only a few of them are validated as relevant
      targets in clinical studies. Estrogen receptor (ER) and HER2 expressions could be
      associated with a level I evidence. Beyond ER and HER2, BRCA and PIK3CA mutations
      (when targeted with alpha-specific PI3K inhibitors) could be considered as
      promising targets in breast cancer since they have been associated with objective
      responses in phase I/II trials. In addition to these four molecular alterations,
      several others have shown promising results in preclinical studies and are being
      investigated in clinical trials. These genomic alterations include AKT1, ERBB2,
      and ESR1 mutations. These considerations highlight the lack of evidence for using
      multiplex technologies to individualize therapy in metastatic breast cancer.
      Sequencing multiple genes to treat metastatic breast cancer is very promising but
      should be done in the context of clinical trials, either to enrich phase I/II
      trials in patients with genomic alterations or to show medical usefulness of new
      biotechnologies like next-generation sequencing (NGS). Although most current
      approaches of precision medicine are aiming at targeting drivers, additional
      applications could be developed in the future. This includes the identification
      of DNA repair deficiencies, mechanisms of immune suppression, and identification
      of minority lethal subclones. Finally, one of the very promising applications of
      genomics for metastatic breast cancer is the identification of pathway activation
      or defects at the individual level. For example, gene expression and single
      nucleotide polymorphisms (SNP) signatures are being developed to detect kinase
      (such as mammalian target of rapamycin [mTOR]/CDK4) activations or DNA repair
      deficiencies. 

PMID- 25993175
TI  - Treatment of peritoneal carcinomatosis of colorectal origin.
AB  - The management of peritoneal carcinomatosis from colon cancer remains a
      controversial issue. Peritoneal carcinomatosis is associated with worse survival
      and has led to an aggressive treatment that combines surgery and intraperitoneal
      chemotherapy (IPC). This review will describe the rationale behind this treatment
      and the current controversy surrounding it. 

PMID- 25993176
TI  - Hepatocellular carcinoma tumor board: making sense of the technologies.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, with a
      rising global incidence. The vast majority of HCC cases occur in the setting of
      liver cirrhosis, mainly due to chronic hepatitis C (HCV) or hepatitis B (HBV)
      viral infections, alcohol consumption, and nonalcoholic fatty liver disease. The
      new approval of curative therapy with two NS5A inhibitors, ledipasvir and
      sofosbuvir, for the treatment of HCV will no doubt affect HCC incidence and
      outcome. No studies have evaluated the use of the new antivirals in patients with
      HCC. Staging and scoring remain an integral part of the management of patients
      with advanced HCC. Curative therapies for the treatment of HCC are evolving.
      Improvements in surgical techniques and risk stratification for orthotopic liver
      transplantation (OLT) have expanded access and improved the outlook for patients
      suffering from HCC. Interventional locoregional treatments continue to play a key
      role in the management of HCC. Transarterial chemoembolization is considered the
      standard of care for patients with noninvasive multinodular tumors at the
      intermediate stage. Bland embolization appears to have similar virtues in some
      studies. Y90 radioembolization represents a promising treatment option for
      patients unfit or refractory to transarterial chemoembolization. The advent of
      sorafenib as a standard of care with an improvement in survival sadly remain the
      only major breakthrough in the treatment of advanced HCC, with mounting negative
      data from multiple clinical trials. Advances in immunotherapy and customized
      therapy may hopefully help reverse this tide. 

PMID- 25993178
TI  - Current and future care of patients with the cancer anorexia-cachexia syndrome.
AB  - Many important advances have occurred in the field of cancer cachexia over the
      past decade, including progress in understanding the mechanisms of the cancer
      anorexia-cachexia syndrome (CACS) and the development of promising pharmacologic
      and supportive care interventions. However, no approved agents for cancer
      cachexia currently exist, emphasizing the unmet need for an effective
      pharmacologic therapy. This article reviews the key elements of CACS assessment
      in daily practice, the contribution of nutritional impact symptoms (NIS), the
      evidence for current pharmacologic options, and promising anticachexia agents in
      perclinical and clinical trials. It also proposes a model for multimodality
      therapy and highlights issues pertinent to CACS in patients with pancreatic,
      gastric, and esophageal cancer. 

PMID- 25993177
TI  - Making sense of current and emerging therapies in pancreatic cancer: balancing
      benefit and value.
AB  - Pancreatic cancer remains the fourth leading cause of cancer deaths in the United
      States with a dismal prognosis and a 5-year survival of less than 5% across all
      stages.(1) In 2014, there were approximately 46,420 new cases of pancreatic
      cancer with only 9% of patients having localized disease.(2) Given that the vast
      majority of patients present with advanced disease, much of the focus for drug
      development has been in the metastatic setting, which is evident with the advent
      of two combination chemotherapy regimens for this indication. Although
      conventional cytotoxic chemotherapy remains the standard of care, an ongoing
      search for novel therapeutic approaches continues. We will highlight several new
      approaches here, with a particular emphasis on immunotherapeutic strategies. We
      will also introduce concepts regarding the potential economic effects associated
      with the development and implementation of new treatments in pancreatic cancer. 

PMID- 25993179
TI  - Challenging the treatment paradigm for advanced renal cell carcinoma: a review of
      systemic and localized therapies.
AB  - The current standard of care for the management of advanced renal cell carcinoma
      (RCC) revolves around systemic therapy with molecularly targeted agents. Over the
      last decade, a total of seven targeted drugs have been approved but, altogether,
      only exploit two molecular targets in this disease: the vascular endothelial
      growth factor (VEGF) axis and the mammalian target of rapamycin (mTOR).
      Introduction of these agents has markedly improved outcomes compared with those
      in the cytokine era, yet comparatively little progress has been made since
      registration of the first targeted therapeutics occurred 10 years ago. In this
      article, we review efforts to improve on this current treatment paradigm. We
      discuss novel targets in this disease and corresponding new agents under
      investigation. The article dedicates particular attention to targeted
      immunotherapeutics, which are rapidly emerging as a new category of interest in
      this disease. Last, we review current data supporting the use of surgical
      interventions to improve outcomes in patients with metastatic disease. 

PMID- 25993180
TI  - The Role of Surveillance versus Adjuvant Treatment in Stage I Germ Cell Tumors:
      Outcomes and Challenges.
AB  - Germ cell cancers of the testis arise in young adults, and, if identified in
      stage I, have an excellent prognosis. Thus, we should minimize management-related
      toxicities. Surveillance (observation) following orchiectomy can avoid further
      treatment; however, patients who experience relapse receive more treatment than
      what would have been used during initial adjuvant therapy. For the individual
      patient, it is important to be aware of their particular risk of relapse, the
      treatment they would receive for the treatment of relapse and the alternative
      adjuvant approaches. For seminoma, the risk of relapse during surveillance is 15%
      to 20%; the size of the primary tumor and the presence of rete testis invasion
      are prognostic factors. Most relapses occur within 3 years; however,
      approximately 10% occur more than 5 years after orchiectomy. The alternative
      adjuvant strategies are either one cycle of carboplatin or radiotherapy (RT),
      which reduce recurrence risk to less than 5%. The cure rate is around 99%,
      regardless of which management option is implemented. For stage I nonseminoma,
      the risk of relapse during surveillance in unselected series is 26% to 30%.
      Lymphovascular invasion and the amount of embryonal carcinoma are risk factors.
      Most relapses occur within the first year after orchiectomy, and relapse after 3
      years is rare. Ninety percent of relapse patterns are classified as "good
      prognosis," and cure rates are 99%. The alternatives to surveillance include
      adjuvant strategies such as one cycle of adjuvant bleomycin/etoposide/cisplatin
      (BEP) chemotherapy; however, evidence is emerging that a single cycle is
      effective. There is controversy whether to offer surveillance for all patients or
      to offer adjuvant chemotherapy to select patients. 

PMID- 25993181
TI  - Triple-negative breast cancer: immune modulation as the new treatment paradigm.
AB  - Recent studies of tumor lymphocytic immune infiltrates in breast cancer have
      suggested an improved prognosis associated with increasing levels of tumor
      infiltrating lymphocytes (TIL). Triple-negative breast cancer (TNBC) is the
      breast cancer subtype that has the greatest incidence of patients with a robust
      tumor immune infiltrate, although it is still a minority of patients. Elevated
      levels of either intratumoral or stromal T cells are associated with an improved
      overall survival (OS) and disease-free survival (DFS) in TNBC as compared with
      other breast cancer subtypes. TNBC may be immunogenic for several reasons.
      Subtypes of TNBC have a significant number of genetic mutations, and the immune
      system may see the aberrant proteins encoded by these mutations as foreign.
      Moreover, TNBC is associated with a prognostic gene signature that also includes
      B cells. Antibodies secreted by B cells may bind to tumor antigens and amplify
      the adaptive immune response that has already been initiated in the tumor. New
      immune modulatory agents, including immune checkpoint inhibitors, have shown
      activity in immunogenic tumors such as melanoma and bladder cancer and have
      recently been tested in TNBC. The clinical response rates observed, patterns of
      response, and adverse event profiles are similar to what has been described in
      melanoma where this class of agents has already been approved for clinical use in
      some cases. Lessons learned in assessing the immunogenicity of TNBC, potential
      mechanisms of immune stimulation, and response to immune modulatory drugs lay the
      foundation for the development of immune-based therapies in all subtypes of the
      disease. 

PMID- 25993182
TI  - Germ cell tumors: looking to the future.
AB  - Our knowledge about the management of men with germ cell tumors (GCTs) and its
      tumor biology continues to evolve. Vascular disease, metabolic syndrome, second
      malignant neoplasms, and hypogonadism occur after treatment for GCTs and the
      latency pattern resembles that seen in patients treated for Hodgkin lymphoma.
      Patients receiving treatment for GCTs should be informed not only of the near
      term toxicity (experienced during or shortly after administration), but also the
      delayed and late effects of chemotherapy and the need for lifelong surveillance
      for all late outcomes, including late relapse. Recent data suggest that the
      treatment outcome of patients with intermediate-risk, poor-risk, and relapsed
      GCTs can be improved through multicenter trials that include the general oncology
      community. Finally, GCTs are a malignancy of primordial germ cells. Programmed
      differentiation is clinically evident in vivo and probably related to
      chemotherapy resistance. This biology has much clinical relevance, some of which
      is already in use. 

PMID- 25993183
TI  - Salvage therapy in patients with germ cell tumors.
AB  - Testicular cancer is the most curable metastatic solid tumor. Initial
      chemotherapy is evidence based with risk stratification into three prognostic
      categories: good, intermediate, and advanced disease. Guidelines for disease
      management following progression after initial cisplatin combination chemotherapy
      are less clear. Options include salvage surgery for patients with anatomically
      confined relapse, standard-dose cisplatin combination chemotherapy, or high-dose
      chemotherapy with carboplatin plus etoposide with peripheral blood stem cell
      transplantation. Proper interpretation of a presumed relapse can be complicated.
      Growing masses on imaging studies might reflect a growing teratoma. Persistent
      elevations of serum human chorionic gonadotropin (hCG) or alpha fetoprotein (AFP)
      are only an indication for salvage therapy if there is a definitive rise in the
      tumor marker. Elevated and rising serum hCG as the only evidence of recurrence
      can be because of cross reactivity with luteinizing hormone or usage of marijuana
      rather than progressive cancer. Elevated liver function tests can cause rising
      serum AFP. 

PMID- 25993184
TI  - Why Chemotherapy Should be Given Early for Men with Metastatic Prostate Cancer.
AB  - Metastatic hormone-sensitive prostate cancer (mHSPC) is an incurable disease, and
      despite a high response rate to androgen-deprivation therapy (ADT), outcomes have
      not significantly changed for many decades. Earlier attempts at multitargeted
      strategies with the addition of cytotoxic chemotherapy to ADT did not affect
      survival. As more effective therapies are emerging, including cytotoxic therapy
      for patients with metastatic castrate-resistant prostate cancer (mCRPC), there is
      increasing interest for testing these drugs earlier in the disease course. The
      premise is that agents with clinical benefit in advanced mCRPC may have a better
      effect if used preemptively before the development of significant resistance and
      to attack earlier de novo androgen resistant/independent clones. The recent
      results of the phase III clinical trial E3805 investigating ADT with or without
      docetaxel in mHSPC provide compelling support for this strategy. Docetaxel
      combined with ADT significantly improved overall survival from 44 to 57.6 months
      (p=0.0003), particularly in patients with high-volume disease (from 32.2 to 49.2
      months; p=0.0006). Longer follow-up is needed to assess the effect on patients
      with low disease burden. Further studies are needed to further maximize the
      antitumor effect in patients with mHSPC and to investigate the effects of
      advancing therapy to this disease setting on the efficacy of respective agents in
      the castration-resistant setting.

PMID- 25993185
TI  - Radium 223: how can we optimize this new tool for metastatic castration-resistant
      prostate cancer?
AB  - Radium 223 is an alpha-emitting intravenous radiotherapy approved for the
      treatment of men with metastatic castration-resistant prostate cancer (mCRPC).
      The approved indication covers men with pain from bony metastatic disease and no
      visceral involvement; however, questions remain as to optimal patient selection
      and timing of this treatment relative to other life-extending therapies for
      mCRPC. Limited data exist to guide clinicians on how to position radium 223 in
      the therapeutic sequence, however, some theoretical considerations and data
      derived from the ALSYMPCA trial populations pre- and postdocetaxel will be
      outlined. Subgroup analyses may provide some insight into patient selection. 

PMID- 25993186
TI  - Immunotherapeutic approaches in prostate cancer: combinations and clinical
      integration.
AB  - Despite multiple immunologic approaches with peptide, protein, and DNA vaccines,
      no single therapy has induced complete remission or maintained durability of
      response in patients with castration-resistant prostate cancer (CRPC).
      Historically, immunotherapy has had limited effect on solid tumors with the
      exception of melanoma and renal cell carcinomas, which have been deemed as
      immunologic cancers given their potential for remissions either spontaneously or
      after removal of the primary lesion. There is considerable excitement about using
      an immunotherapy in combination with biologic agents such as checkpoint
      inhibitors, cytokines, other vaccines, or chemotherapy. Sipuleucel-T represents
      one of several novel immunologic therapeutic approaches to treat prostate cancer
      in addition to other solid tumors. It is the first in its class of autologous
      cellular therapies to demonstrate safety and an overall survival benefit in
      patients with asymptomatic or minimally symptomatic CRPC and represents a unique
      treatment method that may be further enhanced with other agents. Although
      sipuleucel-T can be used as a foundation on which to build and enhance future
      immunologic clinical trials, other exciting strategies are in development that
      may be easily integrated into the algorithm of current care. 

PMID- 25993187
TI  - Evolving immunotherapy strategies in urothelial cancer.
AB  - The treatment of nonmuscle-invasive urothelial carcinoma with bacillus Calmette
      Guerin (BCG) represents the importance of immunotherapy in the treatment of
      cancer. Despite its clinical efficacy, up to 30% of patients will ultimately
      experience progression to muscle-invasive disease. This, along with an improved
      understanding of the biologic pathways involved, has led to efforts to improve,
      enhance, or alter the immune response in the treatment of urothelial carcinoma. A
      number of novel therapeutic approaches currently are being pursued, including
      recombinant BCG to induce T helper type 1 (Th1) immune responses, nonlive
      Mycobacterium agents, targeted agents toward cancer-associated antigens, immune
      modulating vaccines, and adoptive T-cell therapies. Here, we review the current
      and future immunotherapy treatment options for patients with urothelial cancer. 

PMID- 25993188
TI  - Emerging role for novel immunotherapy agents in metastatic renal cell carcinoma:
      from bench to bedside.
AB  - Therapies that augment the antitumor immune response have been an established
      treatment modality for metastatic renal cell carcinoma (mRCC) since the 1980s. An
      improved understanding of the factors that limit the immune response to cancer
      have led to the development of novel therapeutic agents. Most notably, monoclonal
      antibodies that block the programmed death (PD)-1 immune checkpoint pathway have
      demonstrated encouraging antitumor activity against mRCC in phase I and II
      clinical trials. However, as monotherapy these agents are unlikely to offer
      substantial clinical benefit for the majority of patients with mRCC. Combination
      approaches and improvements in patient selection will be essential to enhance
      their efficacy and ensure the rational application of immunotherapy. This review
      summarizes the clinical and preclinical data that support the use of novel
      immunotherapies for mRCC and looks forward to future directions for this
      promising therapeutic strategy. 

PMID- 25993190
TI  - Triple-negative breast cancer: molecular subtypes and new targets for therapy.
AB  - Triple-negative breast cancer (TNBC) is a molecularly diverse disease. This
      heterogeneity has limited the success of targeted therapy in unselected patients
      to date. Recent transcriptional analysis has divided TNBC into transcriptionally
      similar subtypes that may have different sensitivity to neoadjuvant chemotherapy
      and targeted therapy. At present, chemotherapy is the mainstay of treatment for
      early-stage and advanced TNBC; however, several actionable targets show promise
      in preclinical studies. Novel therapeutic strategies are currently being tested
      in phase II and phase III trials and will likely require patient stratification
      before therapy. Examples of these tailored approaches include poly(ADP-ribose)
      polymerase inhibitors for BRCA-mutated TNBC, antiandrogens for androgen receptor
      (AR)-positive TNBC, fibroblast growth factor receptor (FGFR) inhibitors for TNBC
      harboring FGFR amplifications, and gamma-secretase inhibitors for TNBC with
      mutations in the PEST domain of NOTCH proteins. Treatment of TNBC based on
      molecular subsets represents a potential algorithm for the future. Well-designed
      clinical trials with incorporation of integrated biomarkers are necessary to
      advance the development of molecularly targeted therapy for different subgroups
      of TNBC. 

PMID- 25993191
TI  - Epithelial ovarian cancer in older women: defining the best management approach.
AB  - Epithelial ovarian cancer is a cancer of older women. In fact, almost half of
      women diagnosed with ovarian cancer will be older than age 64, and 25% will be
      older than age 74. Therefore, it is crucial to examine the available data in
      older populations to optimize the therapeutic approach without negatively
      affecting the quality of life permanently. Unfortunately, little prospective data
      are available in this under-represented population of women. Although ovarian
      cancer traditionally has been approached with aggressive cytoreductive surgery,
      older patients may benefit from a less aggressive surgical approach and, in some
      cases, may be candidates for neoadjuvant chemotherapy followed by an interval
      cytoreduction. Modalities do exist for assessing an older woman's ability to
      tolerate surgery and chemotherapy, and these tools should be familiar to
      clinicians who are caring for this population of women in making treatment
      decisions. Ongoing planned trials to evaluate pretreatment assessment for older
      patients will provide objective, feasible, clinical tools for applying our
      treatment-based knowledge. Future trials of both surgery and chemotherapy,
      including a focus on the sequence of these two treatment modalities, are crucial
      to guide decision making in this vulnerable population and to improve outcomes
      for all. 

PMID- 25993189
TI  - Nonsurgical management of cervical cancer: locally advanced, recurrent, and
      metastatic disease, survivorship, and beyond.
AB  - Despite the declining incidence of cervical cancer as a result of the
      introduction of screening programs, globally it remains a leading cause of cancer
      related death in women. Outcomes for patients who are diagnosed with anything but
      early-stage disease remain poor. Here we examine emerging strategies to improve
      the treatment of locally advanced disease. We discuss emerging biologic data,
      which are informing our investigation of new therapeutic interventions in
      persistent, recurrent, and metastatic cervical cancer. We recognize the
      importance of interventions to improve quality of life and to prevent long-term
      sequelae in women undergoing treatment. Finally, and perhaps most importantly, we
      recognize the need for global collaboration and advocacy to improve the outcome
      for all women at risk of and diagnosed with this disease. 

PMID- 25993192
TI  - Research Progress in Head and Neck Squamous Cell Carcinoma: Best Abstracts of
      ICHNO 2015.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous group of
      tumors that develop via one of the two primary carcinogenic pathways: chemical
      carcinogenesis through exposure to tobacco and alcohol or virally induced
      tumorigenesis. HPV-negative (HPV-) and HPV-positive (HPV+) HNSCCs represent
      distinct disease entities, and the latter is associated with a substantially
      improved outcome. Differences in molecular pathogenesis account for these
      different outcomes; their staging classification and therapeutic regimens also
      are currently being re-evaluated, and re-evaluation would be significantly
      facilitated by robust biomarkers for patient stratification. Through the past
      years, with the advent of the omics era, a better understanding of the biology of
      HNSCC has been accompanied by the exploration of a large and rapidly expanding
      number of targeted agents, which might be incorporated into standard management
      in the future. In the era of personalized medicine, and with a view to improve
      the outcomes and quality of life of patients, current research efforts also are
      focused on the identification of specific biomarkers for treatment selection.
      Treatment of HNSCC is expected to change in the next decade if molecular biology
      continues to evolve. Herein, we highlight research progress in HNSCC presented at
      the fifth International Conference on Innovative Approaches in Head and Neck
      Oncology (ICHNO). 

PMID- 25993193
TI  - Comparative effectiveness research in cancer with observational data.
AB  - Observational studies are increasingly being used for comparative effectiveness
      research. These studies can have the greatest impact when randomized trials are
      not feasible or when randomized studies have not included the population or
      outcomes of interest. However, careful attention must be paid to study design to
      minimize the likelihood of selection biases. Analytic techniques, such as
      multivariable regression modeling, propensity score analysis, and instrumental
      variable analysis, also can also be used to help address confounding. Oncology
      has many existing large and clinically rich observational databases that can be
      used for comparative effectiveness research. With careful study design,
      observational studies can produce valid results to assess the benefits and harms
      of a treatment or intervention in representative real-world populations. 

PMID- 25993194
TI  - Cancer care quality: current state and future directions.
AB  - Delivery of high-quality medicine is essential in all fields, but it is
      particularly crucial in cancer medicine in which therapies can be toxic and life
      threatening and appropriate treatment can lead to long-term remissions or cure,
      and when poor therapy compromises survival. Variability in postoperative
      mortality has been demonstrated for several complex cancer surgeries, depending
      on surgical expertise and volumes. Systemic therapy, including both cytotoxic and
      targeted therapies (which are the backbones of many curative regimens), can have
      severe toxicities. Small upward errors in dosing or schedule can result in
      unnecessary morbidity and mortality, and they can result in reduced efficacy and
      poor outcomes. Similarly, radiation therapy is a critical modality in the
      treatment of so many cancers, but clinically important morbidity and mortality
      can be associated with it. Methods to continually assess quality in ways that
      lead to interventions to improve care are essential in cancer medicine today, and
      they can be viewed as an obligation of our profession. 

PMID- 25993195
TI  - The challenges of managing older patients with acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL), predominantly a disease of children, has a
      second incidence peak in older adults. Patients older than age 50 but younger
      than age 65 may be included in trials of intensive treatment with curative
      intent, but their outcome is poor with high nonrelapse mortality (NRM), high
      relapse rates, and low overall survival. Using limited published data from the
      United Kingdom ALL XII and HOVON trials, this manuscript explores the reasons for
      the high transplant-related mortality (TRM) and presents early data from the
      United Kingdom ALL 60+ and United Kingdom ALL XIV studies. Factors affecting
      therapeutic decisions for older patients are discussed. A case study illustrates
      some of the issues involved in managing these patients and the need to
      individualize therapy and consider all options. There may be a role for reduced
      intensity allografting in selected, fitter patients older than age 50; this
      article presents preliminary transplant data from United Kingdom ALL XIV that
      prospectively assesses this therapeutic modality. Detailed discussion of tyrosine
      kinase inhibitors and the potential place of novel targeted antibodies and immune
      T-cell therapies will be not discussed in detail. Finally, there is a description
      of the major outstanding issues and the trials that are needed to inform decision
      making and improve outcome in this challenging group of patients. 

PMID- 25993196
TI  - Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in
      adults: a broader range of options, improved outcomes, and more therapeutic
      dilemmas.
AB  - The article addresses selected key areas of flux in the management of
      Philadelphia chromosome-positive acute lymphoblastic leukemia. There is no doubt
      that tyrosine kinase inhibitors (TKIs) have made a major contribution to higher
      rates of complete remission and that more patients are now surviving long term.
      Many patients tolerate TKIs well, and remission can be achieved with minimal
      toxicity. Because remissions can include a proportion of patients who become BCR
      ABL1 transcript negative, the question of whether allogeneic hematopoietic stem
      cell transplantation can be avoided requires discussion. Despite the major
      progress that has been made and the relative profusion of therapeutic choice
      compared with 10 years ago, evidence is still lacking for many of the major
      possible interventions, and how to combine them is unclear. Because of the rarity
      of the condition and the enticing possibility of increasing traction to therapy,
      clinical trials and international cooperation remain paramount. 

PMID- 25993197
TI  - CD19 CAR Therapy for Acute Lymphoblastic Leukemia.
AB  - Chimeric antigen receptor (CAR) therapy is an emerging immunotherapy that shows
      great promise for cancer, in particular acute lymphoblastic leukemia (ALL). CARs
      are recombinant receptors for antigen, which, in a single molecule, redirect the
      specificity and function of T lymphocytes. Following their genetic transfer to
      patient T cells, the latter acquire the ability to recognize leukemia cells and
      destroy them. Several years ago, we identified CD19 as an attractive target for
      CAR therapy for most B cell malignancies, including ALL. We and others have
      reported remarkable clinical outcomes in adults and children with ALL, achieving
      a high complete remission rate irrespective of age, prior treatments, or other
      prognostic markers. Severe cytokine release may develop in patients with high
      tumor burdens. Several interventions are available to curb the cytokine release
      syndrome when it occurs. Based on the impressive results obtained with CD19 CAR
      therapy for ALL, it is realistic to expect that CD19 CARs will become part of the
      armamentarium for B cell-ALL and other B cell malignancies. 

PMID- 25993198
TI  - New targeted therapies for indolent B-cell malignancies in older patients.
AB  - Molecularly targeted agents have become an established component of the treatment
      of indolent B-cell malignancies (iNHL). iNHL disproportionately affects older
      adults, so treatments that have excellent tolerability and efficacy across
      multiple lines of therapy are in demand. The numbers and classes of targeted
      therapies for iNHL have proliferated rapidly in recent years; classes of agents
      that show promise for older patients with iNHL include anti-CD20 antibodies,
      phosphatidyl-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling
      pathway inhibitors, immunomodulators, proteasome inhibitors, epigenetic
      modulators, and immunotherapies. Here, we review the proposed mechanisms of
      action, efficacy, and tolerability of novel agents for iNHL, with an emphasis on
      their applicability to older patients. 

PMID- 25993199
TI  - Hematopoietic cell transplantation for myelodysplastic syndrome.
AB  - Although high-dose chemotherapy may cure a small subset of patients with
      myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation
      (HCT) is the only currently available modality that is curative in a large
      proportion of patients. Approximately 30% to 40% of patients with high-risk MDS
      and 60% to 80% of patients with low-risk MDS survive long-term in remission.
      Disease classification and risk assessment schemes, such as the World Health
      Organization (WHO) Prognostic Scoring System (WPSS), the Revised International
      Prognostic Scoring System (IPSS-R), and patient characteristics as assessed by
      the HCT Comorbidity Index (HCT-CI) or other scores, provide guidance for patient
      management. First, by defining the prognosis of patients without HCT, these tools
      help physicians decide who should and who should not be transplanted. Second,
      they predict at least in part how successful a transplant is likely to be.
      Pretransplant cytogenetics and marrow myeloblast count are the strongest risk
      factors for post-transplant relapse. The HCT-CI allows physicians to estimate the
      probability of nonrelapse mortality after HCT; recent data suggest that there is
      also a relationship to the development of graft-versus-host disease (GVHD). In
      general, the emphasis has shifted from high-dose therapy, aimed at maximum tumor
      cell kill, to reduced-intensity conditioning (RIC), relying on the donor cell
      mediated graft-versus-tumor (GVT) effects to eradicate the disease. GVT effects
      are most prominent in patients who also develop GVHD, especially chronic GVHD.
      Thus, ongoing work is directed at reducing GVHD while maintaining potent GVT
      effects and at exploiting the growing knowledge of somatic mutations for the
      development of targeted therapies. 

PMID- 25993200
TI  - Diagnosing and managing advanced chronic myeloid leukemia.
AB  - Clinical staging of chronic myeloid leukemia (CML) distinguishes between chronic
      phase (CP-CML), accelerated phase (AP-CML), and blastic phase (BP-CML),
      reflecting its natural history in the absence of effective therapy.
      Morphologically, transformation from CP-CML to AP/BP-CML is characterized by a
      progressive or sudden loss of differentiation. Multiple different somatic
      mutations have been implicated in transformation from CP-CML to AP/BC-CML, but no
      characteristic mutation or combination of mutations have emerged. Gene expression
      profiles of AP-CML and BP-CML are similar, consistent with biphasic evolution at
      the molecular level. Gene expression of tyrosine kinase inhibitor (TKI)-resistant
      CP-CML and second CP-CML resemble AP/BP-CML, suggesting that morphology alone is
      a poor predictor of biologic behavior. At the clinical level, progression to
      AP/BP-CML or resistance to first-line TKI therapy distinguishes a good risk
      condition with survival close to the general population from a disease likely to
      reduce survival. Progression while receiving TKI therapy is frequently caused by
      mutations in the target kinase BCR-ABL1, but progression may occur in the absence
      of explanatory BCR-ABL1 mutations, suggesting involvement of alternative
      pathways. Identifying patients in whom milestones of TKI response fail to occur
      or whose disease progress while receiving therapy requires appropriate molecular
      monitoring. Selection of salvage TKI depends on prior TKI history, comorbidities,
      and BCR-ABL1 mutation status. Despite the introduction of novel TKIs, therapy of
      AP/BP-CML remains challenging and requires accepting modalities with substantial
      toxicity, such as hematopoietic stem cell transplantation (HSCT). 

PMID- 25993201
TI  - Current therapies and their indications for the Philadelphia-negative
      myeloproliferative neoplasms.
AB  - The groundbreaking discovery of the Janus-associated kinase 2 (JAK2) V617F
      mutation 10 years ago resulted in an unprecedented intensive basic and clinical
      research in Philadelphia-negative myeloproliferative neoplasms (MPNs). During
      these years, many new potential targets for therapy were identified that opened
      the era of targeted therapy for these diseases. However, only one new drug
      (ruxolitinib) has been approved during the past 40 years, and, although promising
      new therapies are evaluated, the armamentarium to treat MPN still relies on
      conventional drugs, like cytotoxic agents and anagrelide. The exact role of
      interferon (IFN) alfa still needs to be clarified in randomized studies, although
      it has been shown to be effective in MPNs for more than 25 years. The current
      therapeutic strategy for MPNs is based on the risk of vascular complication,
      which is the main cause of mortality and mortality in the medium term. However,
      the long-term outcome may be different, with an increasing risk of transformation
      to myelodysplastic syndrome or acute leukemia during follow-up times. Medicines
      able to change this natural history have not been clearly identified yet, and
      allogeneic stem cell transplantation currently remains the unique curative
      approach, which is only justified for patients with high-risk myelofibrosis or
      for patients with MPNs that have transformed to myelodysplasia or acute leukemia.

PMID- 25993202
TI  - Myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms: an
      update on risk stratification, molecular genetics, and therapeutic approaches
      including allogeneic hematopoietic stem cell transplantation.
AB  - Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem
      cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias,
      and a variable propensity for leukemic transformation. In recent years there has
      been an explosion of information on the molecular genetic changes underlying
      these disorders. This information has substantial prognostic implications, and
      the influence on therapeutic approaches and the treatment of patients is
      evolving. Allogeneic hematopoietic stem cell transplantation (alloSCT) is the
      only known cure for these diseases, but appropriate patient selection is of
      utmost importance from a risk-benefit perspective. This review focuses on the
      factors influencing risk stratification in MDS and optimal choice of front-line
      therapy in the current era, including the interplay of clinical factors and
      molecular genetic factors, and factors that determine eligibility for alloSCT.
      The myelodysplastic/myeloproliferative diseases also will be discussed, including
      the increasing effort to understand the molecular genetics and natural history of
      these disorders and treatment approaches. 

PMID- 25993203
TI  - Neoadjuvant and Adjuvant Therapy for HER2 Positive Disease.
AB  - Since the initial description of the HER2 proto-oncogene as a poor prognostic
      factor in breast cancer in 1987, to the first randomized trial of a monoclonal
      antibody directed against HER2 in combination with chemotherapy for the treatment
      of metastatic HER2-positive breast cancer published in 2001, to the American
      Society of Clinical Oncology (ASCO) 2005 Annual Meeting in which we saw the
      unprecedented collective presentations demonstrating the dramatic benefit of
      trastuzumab in the adjuvant setting-the clinical landscape of HER2-overexpressing
      breast cancer has forever changed. More recently, there has been increasing use
      of preoperative chemotherapy and anti-HER2 targeted therapies in primary operable
      HER2 disease in the research domain and in clinical practice. In the next few
      years, we will see if dual adjuvant anti-HER2 antibody inhibition produces
      clinically significant improvements in outcome; understand if there is a role of
      small molecule inhibitors of the HER family of receptors either in combination or
      sequential to trastuzumab; further refine the relationship between pathologic
      complete response (pCR) and long-term clinical outcomes; and find predictive
      biomarkers to identify cohorts of patients that may need differential
      combinations and/or durations of anti-HER2 therapies. 

PMID- 25993204
TI  - Beyond "second-line" in non-small cell lung cancer: therapy and supportive care.
AB  - Although there once was a single algorithm for the treatment of patients with
      advanced lung cancer, the modern treatment of advanced lung cancer has multiple
      treatment pathways that depend on multiple factors, including histology and
      molecular subtype of disease. New molecular targets, targeted agents, and modes
      of therapy for patients, including immunotherapy, are being identified at an
      accelerating pace. These advances are changing outcomes and the treatment
      landscape, but they also highlight situations with inadequate data to support the
      use of cytotoxic chemotherapy. In this article, we provide an overview of data
      regarding cytotoxic chemotherapy and targeted therapy and their value after
      second line, review the critical role of supportive care and palliative care, and
      emphasize the importance of advance care planning with our patients. Although
      this article focuses primarily on NSCLC, the comments about palliative care and
      advanced care planning also apply to patients with small cell lung cancer. 

PMID- 25993205
TI  - Expectations in the care of lung cancer.
AB  - One of the main challenges oncologists face in the care of patients with lung
      cancer is the decision to incorporate new clinical trial data into routine
      clinical practice. Beyond the question of statistical significance, which is a
      more objective metric, are the results meaningful and applicable to a broader
      population? Furthermore, in an era of value care, do the results justify a
      potential increase in costs? This article discusses the main points that
      clinicians consider in their decision-making process and illustrates the
      arguments with real-life examples. 

PMID- 25993206
TI  - The Value of Lung Cancer CT Screening: It Is All about Implementation.
AB  - Hospitals have been gradually implementing new lung cancer CT screening programs
      following the release of the U.S. Preventive Services Task Force grade B
      recommendation to screen individuals at high risk for lung cancer. Policy makers
      have legitimately questioned whether adoption of CT screening in the community
      will reproduce the mortality benefits seen in the National Lung Screening Trial
      (NLST) and whether the benefits of screening will justify the potentially high
      costs. Although three annual CT screening exams proved cost-effective for the
      patient population enrolled in the NLST, uncertainty still exists about whether
      CT screening will be cost-effective in practice. The value of CT screening will
      depend largely on the strategies used to implement it. This manuscript reviews
      the current reimbursement policies for CT screening and explains the relationship
      between implementation strategies and screening value on the basis of the NLST
      cost-effectiveness analysis and other published data. A subsequent discussion
      ensues about the potential implementation inefficiencies that can negatively
      affect the value of CT screening (e.g., selection of low-risk individuals for
      screening, inappropriate follow-up visits for screening-detected lung nodules,
      failure to offer smoking cessation interventions, and overuse of medical
      resources for clinically irrelevant incidental findings) and the actions that can
      be taken to mitigate these inefficiencies and increase the value of screening. 

PMID- 25993207
TI  - The Latest in Surgical Management of Stage IIIA Non-Small Cell Lung Cancer: Video
      Assisted Thoracic Surgery and Tumor Molecular Profiling.
AB  - Stage IIIA non-small cell lung cancer (NSCLC) remains a treatment challenge and
      requires a multidisciplinary care team to optimize survival outcomes. Thoracic
      surgeons play an important role in selecting operative candidates and assisting
      with pathologic mediastinal staging via cervical mediastinoscopy, endobronchial
      ultrasound, or esophageal ultrasound with fine needle aspiration. The majority of
      patients with stage IIIA disease will receive induction therapy followed by
      repeat staging before undergoing lobectomy or pneumonectomy; occasionally, a
      patient with an incidentally found, single-station microscopic IIIA tumor will
      undergo resection as the primary initial therapy. Multiple large clinical trials,
      including SWOG-8805, EORTC-8941, INT-0139, and ANITA, have shown 5-year overall
      survival rates of up to 30% to 40% using triple-modality treatments, and the best
      outcomes repeatedly are seen among patients who respond to induction treatment or
      who have tumors amenable to lobectomy instead of pneumonectomy. The need for a
      pneumonectomy is not a reason to deny patients an operation, because current
      operative mortality and morbidity rates are acceptably low at 5% and 30%,
      respectively. In select patients with stage IIIA disease, video-assisted thoracic
      surgery and open resections have been shown to have comparable rates of local
      recurrence and long-term survival. New developments in genetic profiling and
      personalized medicine are exciting areas of research, and early data suggest that
      molecular profiling of stage IIIA NSCLC tumors can accurately stratify patients
      by risk within this stage and predict survival outcomes. Future advances in
      treating stage IIIA disease will involve developing better systemic therapies and
      customizing treatment plans on the basis of an individual tumor's genetic
      profile. 

PMID- 25993208
TI  - Current Standards and Clinical Trials in Systemic Therapy for Stage III Lung
      Cancer: What Is New?
AB  - Patients with stage III non-small cell lung cancer (NSCLC) comprise a
      heterogeneous group, some of whom have curable disease. Although surgery plays a
      role for some patients, the majority of fit patients will be treated with
      chemotherapy and radiation alone. The optimal therapy for all patients remains
      undefined, but certain principles of care are widely accepted. Specifically,
      concurrent chemoradiation is the standard of care for patients who are able to
      tolerate such therapy, namely those with a good performance status, minimal or no
      weight loss, and adequate end-organ function, including pulmonary reserve. The
      most commonly used chemotherapy regimens given in combination with radiation
      therapy are cisplatin/etoposide or carboplatin/paclitaxel. Studies incorporating
      newer agents have not improved outcomes when compared to these older regimens.
      The merits of chemotherapy administered beyond the conclusion of radiation
      therapy continue to be debated, but thus far randomized phase III trials have not
      provided supporting evidence for this strategy. Incorporating antiangiogenics
      with chemoradiation has proven to be ineffective in some cases and unsafe in
      others. Studies with targeted agents in unselected patient populations with stage
      III disease have also been disappointing. Despite these recent setbacks, however,
      there remains a sound rationale for incorporating molecularly targeted agents
      into chemoradiation regimens in select patient groups or consolidating
      chemoradiation with immunotherapy. Studies that incorporate drugs targeting EGFR,
      ALK, RAS, programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1)
      into the management of patients with stage III NSCLC will be reviewed. 

PMID- 25993209
TI  - ABC, GCB, and Double-Hit Diffuse Large B-Cell Lymphoma: Does Subtype Make a
      Difference in Therapy Selection?
AB  - Personalized therapy for the treatment of patients with cancer is rapidly
      approaching and is an achievable goal in the near future. A substantial number of
      novel targets have been developed into therapeutic agents. There is a substantial
      variability to antitumor activity by novel therapeutics because of the unique
      heterogeneity and biology that exists both between and within lymphoma subtypes.
      Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin
      lymphoma (NHL). Approximately 40% of patients have refractory disease or disease
      that will relapse after an initial response, and the majority of patients with
      relapsed DLBCL will succumb to the disease. There are two major biologically
      distinct molecular subtypes of DLBCL: germinal center B-cell (GCB) and activated
      B-cell (ABC). ABC DLBCL is associated with substantially worse outcomes when
      treated with standard chemoimmunotherapy. In addition to GCB and ABC subtypes,
      double-hit lymphomas (approximately 5% to 10% of patients) and double-expressor
      lymphomas, which overexpress MYC and BCL2 protein, are aggressive DLBCLs and are
      also associated with a poor prognosis. Double-hit lymphomas have concurrent
      chromosomal rearrangements of MYC plus BCL2 (or less likely, BCL6). Advances in
      molecular characterization techniques and the development of novel agents
      targeting specific subtypes of DLBCL have provided a foundation for personalized
      therapy of DLBCL based on molecular subtype. A number of early clinical trials
      evaluating combinations of novel targeted agents with standard chemotherapy (R
      CHOP) have been completed and have demonstrated the feasibility of this approach
      with encouraging efficacy. As such, molecular classification of DLBCL is not only
      important for prognostication, but moves to center stage for personalization of
      therapy for DLBCL. 

PMID- 25993210
TI  - Cell-of-Origin in Diffuse Large B-Cell Lymphoma: Are the Assays Ready for the
      Clinic?
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide and
      consists of a heterogeneous group of cancers classified together on the basis of
      shared morphology, immunophenotype, and aggressive clinical behavior. It is now
      recognized that this malignancy comprises at least two distinct molecular
      subtypes identified by gene expression profiling: the activated B-cell-like (ABC)
      and the germinal center B-cell-like (GCB) groups-the cell-of-origin (COO)
      classification. These two groups have different genetic mutation landscapes,
      pathobiology, and outcomes following treatment. Evidence is accumulating that
      novel agents have selective activity in one or the other COO group, making COO a
      predictive biomarker. Thus, there is now a pressing need for accurate and robust
      methods to assign COO, to support clinical trials, and ultimately guide treatment
      decisions for patients. The "gold standard" methods for COO are based on gene
      expression profiling (GEP) of RNA from fresh frozen tissue using microarray
      technology, which is an impractical solution when formalin-fixed paraffin
      embedded tissue (FFPET) biopsies are the standard diagnostic material. This
      review outlines the history of the COO classification before examining the
      practical implementation of COO assays applicable to FFPET biopsies. The
      immunohistochemistry (IHC)-based algorithms and gene expression-based assays
      suitable for the highly degraded RNA from FFPET are discussed. Finally, the
      technical and practical challenges that still need to be addressed are outlined
      before robust gene expression-based assays are used in the routine management of
      patients with DLBCL. 

PMID- 25993211
TI  - Novel treatments for T-cell lymphoma.
AB  - T-cell lymphomas are a biologically and clinically diverse collection of diseases
      that collectively account for 10% to 15% of non-Hodgkin lymphomas. Unlike B-cell
      lymphomas, the response of T-cell lymphomas to standard anthracycline-containing
      chemotherapy regimens is suboptimal and the prognosis of patients is accordingly
      poor. To address these shortcomings, there has been a proliferation in biologic
      agents with novel mechanisms of action that target surface antigens, signaling
      pathways, or cellular processes. Given the large number of candidate molecules
      showing preclinical promise and the rarity of these diseases, drug development
      for peripheral T-cell lymphoma is challenging. We provide an overview of agents
      that have recently been approved for relapsed/refractory T-cell lymphoma and
      highlight efforts to introduce these agents into front-line treatment protocols
      in combination with chemotherapy. We discuss biologic doublets currently being
      evaluated as "chemotherapy-free" salvage regimens and highlight some of the most
      promising investigational agents in early clinical development. 

PMID- 25993212
TI  - Novel agents in the therapy of Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is a B-cell malignancy that typically has a favorable
      prognosis when treated with chemotherapy, often in combination with radiation
      therapy. The prognosis for patients whose disease relapses or is refractory,
      however, is far less favorable and novel therapies are needed for these patients.
      The unique cellular composition of HL provides a number of opportunities to
      target either the malignant Reed-Sternberg cell or the inflammatory tumor
      microenvironment. Antibody-drug conjugates targeting CD30, small molecule
      inhibitors of cell signaling, and antibodies that inhibit immune checkpoints,
      have all demonstrated activity in HL. Current and future trials are exploring the
      use of these agents in combination with each other and with standard
      chemotherapy. 

PMID- 25993213
TI  - Smoldering multiple myeloma: when to observe and when to treat?
AB  - Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by
      the presence of at least 3 g/dL of serum M-protein and/or 10% to 60% bone marrow
      plasma cell infiltration with no myeloma-defining event. The risk of progression
      to active multiple myeloma (MM) is not uniform and several markers are useful for
      identifying patients at high risk of progression. The definition of the disease
      has recently been revisited and patients with asymptomatic MM at 80% to 90% of
      progression risk at 2 years are now considered to have MM. Although the current
      standard of care is not to treat, a randomized trial in patients with high-risk
      SMM that compared early treatment versus observation demonstrated that early
      intervention resulted in substantial benefits in terms of time to progression and
      overall survival (OS). These findings highlight the need to follow a correct
      diagnosis by an accurate risk stratification to plan an optimized follow-up
      according to the risk of disease progression. 

PMID- 25993214
TI  - Multiple myeloma: is it time for biomarker-driven therapy?
AB  - Remarkable strides have been made in understanding the molecular mechanisms by
      which multiple myeloma develops, leading to more sophisticated classification
      that incorporates not only the traditional diagnostic criteria, but also
      immunophenotype, genetic, and molecular features. However, even with this added
      information, considerable heterogeneity in clinical outcomes exists within the
      identified subtypes. The present paradigm for myeloma treatment is built on the
      basic step of defining transplant eligibility versus noneligibility, as
      determined by age, performance status, and cumulative burden of comorbidities. An
      incredibly complex heterogeneous disease is, therefore, treated in a generalized
      way with the result that large interpatient variability exists in the outcome. As
      antimyeloma therapeutics continue to expand it is becoming even more crucial to
      personalize treatment approaches that provide the most value to a specific
      patient. Development of biomarkers, either individually or as larger sets or
      patterns and ranging from analysis of blood or bone marrow to biomedical imaging,
      is a major focus in the field. Biomarkers such as involved serum free light chain
      ratio and MRI focal lesions have been implemented in the new definition of
      multiple myeloma and guide clinicians to initiate treatment in otherwise
      asymptomatic individuals. Currently, however, there is not enough evidence to
      support intensifying the treatment for high-risk disease or reducing the
      treatment for low-risk disease. Minimal residual disease-negative status is an
      important biomarker that holds promise for monitoring the effectiveness of
      response-adapted strategies. This article sheds light on the forward landscape
      and rear-mirror view of biomarkers in myeloma. 

PMID- 25993215
TI  - Addressing barriers to uptake of breast cancer chemoprevention for patients and
      providers.
AB  - Breast cancer is the most common malignancy among women in the United States, and
      the primary prevention of this disease is a major public health issue. Because
      there are relatively few modifiable breast cancer risk factors, pharmacologic
      interventions with antiestrogens have the potential to significantly affect the
      primary prevention setting. Breast cancer chemoprevention with selective estrogen
      receptor modulators (SERMs) tamoxifen and raloxifene, and with aromatase
      inhibitors (AIs) exemestane and anastrozole, is underutilized despite several
      randomized controlled trials demonstrating up to a 50% to 65% relative risk
      reduction in breast cancer incidence among women at high risk. An estimated 10
      million women in the United States meet high-risk criteria for breast cancer and
      are potentially eligible for chemoprevention, but less than 5% of women at high
      risk who are offered antiestrogens for primary prevention agree to take it.
      Reasons for low chemoprevention uptake include lack of routine breast cancer risk
      assessment in primary care, inadequate time for counseling, insufficient
      knowledge about antiestrogens among patients and providers, and concerns about
      side effects. Interventions designed to increase chemoprevention uptake, such as
      decision aids and incorporating breast cancer risk assessment into clinical
      practice, have met with limited success. Clinicians can help women make informed
      decisions about chemoprevention by effectively communicating breast cancer risk
      and enhancing knowledge about the risks and benefits of antiestrogens. Widespread
      adoption of chemoprevention will require a major paradigm shift in clinical
      practice for primary care providers (PCPs). However, enhancing uptake and
      adherence to breast cancer chemoprevention holds promise for reducing the public
      health burden of this disease. 

PMID- 25993217
TI  - Prognostic factors and the role of adjuvant radiation therapy in non-melanoma
      skin cancer of the head and neck.
AB  - Non-melanoma skin cancer (NMSC) is the most common cancer worldwide. Among the
      two types of NMSC, basal cell carcinoma (BCC) accounts for approximately 75% to
      80% of cases and cutaneous squamous cell carcinoma (cSCC) accounts for 20% to 25%
      of cases. The majority of lesions are low risk and treated with simple surgical
      excision, which provides histopathologic information and is associated with high
      cure rates and acceptable cosmetic and functional outcomes. cSCCs are generally
      more aggressive than BCCs. NMSC commonly occurs in the sun-exposed head and neck
      region (80% to 90%). Approximately 5% of patients with NMSC (mainly cSCC) will
      have clinicopathologic features that predict for an increased risk for local and
      regional recurrence and, rarely, distant relapse. These features include locally
      advanced primary disease (stage T3-T4), regional nodal involvement, clinical
      perineural invasion, recurrent disease following treatment, and
      immunosuppression. Patients who have these features may warrant review by a
      multidisciplinary tumor board and might require combined modality treatment
      involving surgery and adjuvant radiation therapy (RT). This article focuses on
      our current understanding of the prognostic factors and role of adjuvant RT in
      high-risk NMSC of the head and neck. 

PMID- 25993216
TI  - Multiple myeloma: from front-line to relapsed therapies.
AB  - Recent developments in the treatment of multiple myeloma (MM) have led to
      improvements in response rates and to increased survival. A major advance in the
      last decade has been the introduction of the novel agents thalidomide,
      bortezomib, and lenalidomide as part of front-line treatment in both the
      transplant and nontransplant settings. However, disease relapse is inevitable for
      the majority of patients and myeloma typically recurs more aggressively with each
      relapse, eventually leading to the development of treatment-refractory disease.
      Several phase II and III trials have demonstrated the efficacy of recently
      approved agents in the setting of relapsed and relapsed and refractory MM,
      including pomalidomide and carfilzomib. Ixazomib, an oral proteasome inhibitor,
      and multiple other novel classes of agents are being investigated. These include
      monoclonal antibodies and histone deacetylase inhibitors, which may further add
      to the therapeutic armamentarium for this malignancy. Therefore, in a disease
      characterized by multiple relapses, the optimal sequencing of the different
      effective options is an important consideration in attempting to prolong
      survival. 

PMID- 25993218
TI  - Merkel cell carcinoma: emerging biology, current approaches, and future
      directions.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous cancer that
      predominantly occurs in patients who are older, and is associated with a high
      rate of distant failure and mortality. Current management strategies that
      incorporate surgery and radiotherapy achieve high rates of locoregional control,
      but distant failure rates remain problematic, highlighting the need for new
      effective systemic therapies. Chemotherapy can achieve high response rates of
      limited duration in the metastatic setting, but its role in definitive management
      remains unproven. Recent developments in our knowledge about the biology of MCC
      have led to the identification of new potential therapeutic targets and
      treatments. A key finding has been the discovery that a human polyomavirus may be
      a causative agent. However, emerging data suggests that MCC may actually be two
      distinct entities, viral-associated and viral-negative MCC, which is likely to
      have implications for the management of MCC in the future and for the development
      of new treatments. In this review, we discuss recent discoveries about the
      biology of MCC, current approaches to management, and new therapeutic strategies
      that are being investigated. 

PMID- 25993219
TI  - Perfusion and infusion for melanoma in-transit metastases in the era of effective
      systemic therapy.
AB  - The management of melanoma in-transit metastases (IT-mets) is challenging. For
      many years, the absence of effective systemic therapy has prompted physicians to
      focus on regional therapies for melanoma confined to the limb. The introduction
      of isolated limb perfusion (ILP) and isolated limb infusion (ILI) has enabled
      effective delivery of cytotoxic drugs in an isolated circuit, so as to overcome
      systemic toxicity and maximize local response. Both techniques have evolved over
      years and both tumor necrosis factor (TNF)-alpha-based ILP and ILI have distinct
      indications. The development of new systemic treatment options for patients with
      melanoma in the past decade has shed a new light on melanoma therapy. The present
      manuscript focuses on the modern role of ILI and ILP in the treatment of patients
      with melanoma with in-transit metastases in the era of effective systemic
      therapy. The response and control rates of ILI/ILP are still superior to rates
      achieved with systemic agents. The extent of disease in patients with stage III
      disease, however, warrants effective systemic treatment to prolong survival.
      There is great potential in combining rapid response therapy such as ILI/ILP with
      systemic agents for sustainable response. Trial results are eagerly awaited. 

PMID- 25993220
TI  - Neoadjuvant therapy for melanoma: a promising therapeutic approach and an ideal
      platform in drug development.
AB  - Patients with locoregionally advanced but surgically operable melanoma continue
      to carry a high risk of relapse and death despite the best available standard
      management approaches. Neoadjuvant studies targeting this patient population
      tested chemotherapy with temozolomide and biochemotherapy (BCT), in which BCT
      demonstrated high tumor response rates but was eventually abandoned with the
      failure of BCT to deliver survival benefits in randomized trials of metastatic
      disease. Smaller neoadjuvant immunotherapy studies with interferon (IFN) alfa and
      ipilimumab have yielded promising clinical activity and important mechanistic
      insights and biomarker findings. Newer targeted and immunotherapeutic agents and
      combinations currently are being translated into the neoadjuvant setting at an
      accelerated pace and carry significant clinical promise. In drug development, the
      neoadjuvant approach allows access to blood and tumor tissue before and after
      initiation of systemic therapy, which allows for the conduct of novel mechanistic
      and biomarker studies in the circulation and the tumor microenvironment. Such
      studies may guide drug development and allow for the discovery of predictive
      biomarkers selected on the basis of their capacity to classify patients according
      to the degree of benefit from treatment or the risk for significant toxicity. 

PMID- 25993221
TI  - Treating older adults with cancer: geriatric perspectives.
AB  - The proportion of older adults (age 65 and older) in oncology practices continues
      to increase. Older adults present with unique issues that complicate management
      decisions and evidence from randomized clinical trials to inform management of
      these patients is lacking. Despite this, principles of geriatric medicine need to
      be incorporated into oncology practice to provide optimal individualized care to
      patients. There is increasing evidence from observational studies that geriatric
      assessment (GA) strategies can be applied in oncology, can help predict treatment
      outcomes, and can inform supportive care management for older adults. In this
      review, we discuss the principles of GA and their use in older adults with
      cancer. In addition, considerations on when to refer to a geriatrician and issues
      related to management of vulnerable older adults will be addressed. 

PMID- 25993222
TI  - Chemotherapy-induced peripheral neurotoxicity in cancer survivors: an
      underdiagnosed clinical entity?
AB  - Systemic chemotherapy is a cornerstone of the modern medical management of
      cancer, although its use is limited by toxicity on normal tissues and organs,
      including the nervous system. Long-surviving or cured people strongly require a
      high level of wellness in addition to prolongation of life (the concept of the
      quality of survival), but neurologic dysfunction can severely affect daily life
      activities. Chemotherapy-related peripheral neurotoxicity is becoming one of the
      most worrisome long-term side effects in patients affected by a neoplasm. The
      central nervous system has a limited capacity to recover from injuries, and it is
      not surprising that severe damage can determine long-term or permanent neurologic
      dysfunction. However, the peripheral nervous system also can be permanently
      damaged by anticancer treatments despite its better regeneration capacities, and
      the effect on patients' daily life activities might be extremely severe. However,
      only recently, the paradigms of peripheral neurotoxicity reversibility have been
      scientifically challenged, and studies have been performed to capture the
      patients' perspectives on this issue and to measure the effect of peripheral
      neurotoxicity on their daily life activities. Despite these efforts, knowledge
      about this problem is still largely incomplete, and further studies are necessary
      to clarify the several still-unsettled aspects of long-term peripheral
      neurotoxicity of conventional and targeted anticancer chemotherapy. 

PMID- 25993223
TI  - Sexual healing in patients with prostate cancer on hormone therapy.
AB  - Since prostate cancer becomes more common with age, at least one-third of men
      have sexual problems at diagnosis. All localized treatments for prostate cancer
      greatly increase the prevalence of sexual dysfunction, which include loss of
      desire, erectile dysfunction, and changes in orgasm. Even men on active
      surveillance have a higher rate of problems than matched peers without prostate
      cancer. However, men given androgen deprivation therapy (ADT) have the worst
      rates of sexual dysfunction. Even after 3 to 4 months of ADT, men's desire for
      sex is decreased and irreversible damage may occur to the erectile tissue in the
      penis. Erections do not recover in about one-half of men, even if ADT is
      discontinued. Although intermittent ADT allows some recovery of sexual function,
      serum testosterone requires 9 to 12 months off ADT to recover. Again, one-half of
      men have permanent erectile dysfunction. If ADT causes atrophy of the erectile
      tissue, blood leaks out of the venous system during erection. This syndrome is
      difficult to treat except with surgery to implant a penile prosthesis. Despite
      the high rate of sexual problems in men on ADT, a small group stays sexually
      active and is able to have reliable erections. To improve men's sexual
      satisfaction on ADT, it may be important to educate them about getting extra
      mental and physical sexual stimulation, as well as using penile rehabilitation
      during hormone therapy. Information on reaching orgasm and coping with problems
      such as dry orgasm, pain with orgasm, and urinary incontinence during sex also
      should be provided. 

PMID- 25993224
TI  - Bone health in adults treated with endocrine therapy for early breast or prostate
      cancer.
AB  - Bone is a hormonally responsive organ. Sex hormones and calcium regulating
      hormones, including parathyroid hormone, 1-25 dihydroxy vitamin D, and
      calcitonin, have effects on bone resorption and bone deposition. These hormones
      affect both bone quality and bone quantity. The sex hormone estrogen inhibits
      bone resorption, and estrogen therapy has been developed to prevent and treat
      osteoporosis. Androgens are an important source of estrogen through the action of
      the enzyme aromatase and may themselves stimulate bone formation. Hence, the sex
      steroids play a role in bone metabolism. Breast cancer and prostate cancer are
      frequently hormonally responsive and may be treated with antiestrogens or
      antiandrogens respectfully. In addition, chemotherapy and supportive medications
      may alter the patient's endocrine system. In general, the suppression of sex
      hormones has a predictable affect on bone health, as seen by loss of bone mineral
      density and increased risk of fragility fractures. The bone toxicity of cancer
      directed endocrine therapy can be mitigated through screening, counseling on
      optimization of calcium and vitamin D intake, exercise, and other
      lifestyle/behavioral actions, as well as the use of medications when the fracture
      risk is high. Maintaining bone health in patients who are treated with endocrine
      therapy for breast and prostate cancer is the focus of this review. 

PMID- 25993225
TI  - Endocrine therapy and its effect on sexual function.

PMID- 25993226
TI  - Assuring Quality Cancer Survivorship Care: We've Only Just Begun.
AB  - Clinical practice guidelines, quality metrics, and performance improvement
      projects are the key tools of the national movement to improve and assure quality
      cancer care. Each of these evaluation instruments is intended to assess quality
      from a unique perspective, including that of the individual provider, the
      practice/hospital, and the health care system. A number of organizations have
      developed or endorsed quality measures specific to cancer, however, these have
      not formally included survivorship measures. Fortunately, the American Society of
      Clinical Oncology (ASCO), the National Comprehensive Cancer Network, the American
      Cancer Society, and the American College of Surgeons (ACoS) have taken a
      leadership role in developing survivorship guidelines and quality metrics. Both
      ASCO and ACoS have focused their efforts on the treatment summary and care plan,
      a document that was proposed in the 2006 Institute of Medicine report on cancer
      survivorship. ASCO has proposed a care plan template for implementation and
      incorporation into the electronic health records (EHR), which will lend itself to
      structure, process, and outcome measurement. ACoS, conversely, has included the
      care plan in its cancer program standards with annual evaluation metrics. In
      addition, ASCO has developed a number of key survivorship-relevant metrics as
      part of its Quality Oncology Practice Initiative (QOPI), a tool developed to
      measure quality cancer care and assess adherence to guidelines across academic
      and community practices. Together, these efforts will direct us to more effective
      ways to disseminate guideline recommendations and to better methods of assessing
      quality survivorship care nationally. 

PMID- 25993227
TI  - Decision making in the context of breast cancer chemoprevention: patient
      perceptions and the meaning of risk.
AB  - Chemoprevention with selective estrogen receptor modulators (SERMs) is considered
      one of the most promising risk reduction options to date in the United States.
      Tamoxifen and raloxifene are both approved by the U.S. Food and Drug
      Administration (FDA) for breast cancer risk reduction. However, despite
      endorsement from the American Society for Clinical Oncology and the National
      Comprehensive Cancer Network, uptake remains low. Decision aids have been
      successful in improving women's understanding and knowledge about the risk
      benefit trade-offs in decision making regarding SERMs. However, increased
      knowledge does not lead to increased uptake of chemoprevention for the purpose of
      reducing breast cancer risk; instead, women become more reluctant to take
      medication that is itself associated with risks. Reasons for this include a lack
      of awareness that SERMs are effective in reducing breast cancer risk, an
      unwillingness to increase the risk of other disease, reluctance to take a daily
      medication, and the perception of tamoxifen as a "cancer drug." In studies on
      hypothetical decision making in the context of chemoprevention women indicate
      greater willingness to take a SERM when they are determined to be at risk. These
      findings suggest a differential understanding of what risk means among the
      general public, health professionals, and researchers. Feeling at risk is related
      to bodily signs and symptoms and not to population-derived probabilities. Such
      differential understanding may in part explain women's perception of the low
      efficacy of SERMs and their decision making regarding SERM use. 

PMID- 25993228
TI  - Cancer pain management: safe and effective use of opioids.
AB  - Pain remains a serious consequence of cancer and its treatment. Although
      significant advances have been made in providing effective cancer pain control,
      barriers persist. Lack of knowledge, limited time, financial restrictions, and
      diminished availability of necessary medications serve as significant obstacles.
      Safe and effective opioid use in a patient with cancer requires skill to overcome
      these challenges. Understanding the mechanism of action, along with the
      pharmacokinetics and pharmacodynamics, of opioids will lead to appropriate
      selection, dosing, and titration of these agents. Rotation from one opioid or
      route to another is an essential proficiency for oncologists. As opioid-related
      adverse effects often occur, the oncology team must be expert in preventing and
      managing constipation, nausea, sedation, and neurotoxicities. An emerging concern
      is overtreatment-the excessive and prolonged use of opioids in patients when
      these agents may produce more harm than benefit. This can occur when opioids are
      used inappropriately to treat comorbid psychologic issues such as anxiety and
      depression. Recognizing risk factors for overuse along with key components of
      universal precautions will promote safe use of these medications, supporting
      adherence and preventing diversion, thereby protecting the patient, the
      prescriber, and the community. Because substance use disorders are not rare in
      the oncology setting, attention must be given to the balance of providing
      analgesia while limiting harm. Caring for patients with substance misuse requires
      compassionate, multidisciplinary care, with input from supportive
      oncology/palliative care as well as addiction specialists. 

PMID- 25993229
TI  - State of the art discovery with tumor profiling in pediatric oncology.
AB  - It is an exciting era in pediatric oncology with the advent of new technologies
      to comprehensively characterize cancer genomes in childhood tumors. Defining the
      genetic landscape of pediatric tumors has not only provided critical insight into
      tumor evolution, but it has also offered promise for more effective treatment in
      some cases, such as Philadelphia chromosome-positive acute lymphoblastic leukemia
      (ALL) and anaplastic lymphoma kinase (ALK)-mutated tumors. However, several
      challenges remain as the field of genomic tumor profiling emerges. This new
      technology is costly, and the overall impact on survival has yet to be
      determined. Tumor heterogeneity and clonal evolution have also presented
      challenges in the development of targeted therapy. In this article, we review
      breakthroughs in gene sequencing methodology and discuss examples where genomic
      discoveries have resulted in the recognition of tumor susceptibility as well as
      incorporation of targeted therapy. We also discuss how broad scale comprehensive
      tumor analyses have demonstrated the convergence of individual genetic
      alterations on common relevant pathways. Although the impact of tumor profiling
      is best studied within the context of rigorously designed clinical trials, there
      is promise that there will be growing opportunities for the adaption of precision
      medicine in pediatric oncology in the future. 

PMID- 25993230
TI  - Advances in website information resources to aid in clinical practice.
AB  - The World Wide Web, which has been widely implemented for roughly two decades, is
      humankind's most impressive effort to aggregate and organize knowledge to date.
      The medical community was slower to embrace the Internet than others, but the
      majority of clinicians now use it as part of their everyday practice. For the
      practicing oncologist, there is a daunting quantity of information to master. For
      example, a new article relating to cancer is added to the MEDLINE database
      approximately every 3 minutes. Fortunately, Internet resources can help organize
      the deluge of information into useful knowledge. This manuscript provides an
      overview of resources related to general medicine, oncology, and social media
      that will be of practical use to the practicing oncologist. It is clear from the
      vast size of the Internet that we are all life-long learners, and the challenge
      is to acquire "just-in-time" information so that we can provide the best possible
      care to our patients. The resources that we have presented in this article should
      help the practicing oncologist continue along the path of transforming
      information to knowledge to wisdom. 

PMID- 25993231
TI  - The past, present, and future of patient-reported outcomes in oncology.
AB  - Patient-reported outcomes capture a unique and important perspective of oncology
      therapy. Surveys to properly capture patient-reported outcome measures have been
      under development for more than 2 decades. More recent efforts to understand the
      clinical significance of patient-reported outcomes, called performance measures,
      are underway. Patient-reported outcomes can be used in a variety of ways,
      including therapy decisions for an individual patient, payment for treatment,
      research into disease progression, or new drug development. Technology has
      already enabled electronic systems to capture and search patient-reported
      outcomes and in the future will assist in capturing everyday activities, which,
      in combination with improved informatics to sort the meaningful and actionable
      information, will reduce the time commitment for both patients and providers. 

PMID- 25993232
TI  - Clinical oncology practice 2015: preparing for the future.
AB  - The clinical practice of oncology has become increasingly complex. An explosion
      of medical knowledge, increased demands on provider time, and involved patients
      have changed the way many oncologists practice. What was an acceptable practice
      model in the past may now be relatively inefficient. This review covers three
      areas that address these changes. The American Society of Clinical Oncology
      (ASCO) National Oncology Census defines who the U.S. oncology community is, and
      their perceptions of how practice patterns may be changing. The National Cancer
      Institute (NCI)-ASCO Teams in Cancer Care Project explores how best to employ
      team science to improve the efficiency and quality of cancer care in the United
      States. Finally, how physician assistants (PAs) and nurse practitioners (NPs)
      might be best integrated into team-based care in oncology and the barriers to
      integration are reviewed. 

PMID- 25993233
TI  - Adjuvant chemotherapy for soft tissue sarcoma.
AB  - Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS).
      However, when the risk of relapse is high, it is an option for shared decision
      making with the patient in conditions of uncertainty. This is because available
      evidence is conflicting, even if several randomized clinical trials have been
      performed for 4 decades and also have been pooled into meta-analyses. Indeed,
      available meta-analyses point to a benefit in the 5% to 10% range in terms of
      survival and distant relapse rate. Some local benefit also was suggested by some
      trials. Placing chemotherapy in the preoperative setting may help gain a local
      advantage in terms of the quality of surgical margins or decreased sequelae. This
      may be done within a personalized approach according to the clinical
      presentation. Attempts to personalize treatment on the basis of the variegated
      pathology and molecular biology of STS subgroups are ongoing as well, according
      to what is done in the medical treatment of advanced STS. Thus, decision making
      for adjuvant and neoadjuvant indications deserves personalization in clinical
      research and in clinical practice, taking profit from all multidisciplinary
      clinical skills available at a sarcoma reference center, though with a degree of
      subjectivity because of the limitations of available evidence. 

PMID- 25993234
TI  - Adjuvant radiation for soft tissue sarcomas.
AB  - Over recent decades, limb-preservation surgery in combination with radiotherapy
      achieves local control rates exceeding 90% for extremity soft tissue sarcoma
      (STS). Local control is not as successful for retroperitoneal sarcoma
      (approximately 60%) despite aggressive surgical approaches including en bloc
      resection of uninvolved adjacent organs combined with intensity modulated
      radiotherapy (IMRT). This review will discuss the indications for adjuvant
      radiation therapy (RT) for primary presentation of soft tissue sarcoma: "What,"
      referring to the type and manner of planning and delivery of RT; "When,"
      referring to the timing and scheduling of RT; and "Why," referring to the
      rationale for the use of RT will be addressed. From a practical stand point, this
      Educational Chapter on "adjuvant RT" will focus on pre- and postoperative RT in
      the context of gross total resection for extremity and retroperitoneal soft
      tissue sarcoma, the two most frequent paradigms for the use of adjuvant RT. 

PMID- 25993235
TI  - Systemic therapy for osteosarcoma and Ewing sarcoma.
AB  - Curative therapy for both osteosarcoma and Ewing sarcoma requires the combination
      of effective systemic therapy and local control of all macroscopic tumors.
      Systemic therapy for osteosarcoma consists of multiagent chemotherapy. The most
      common regimen uses cisplatin, doxorubicin, and high-dose methotrexate. Addition
      of ifosfamide and etoposide to treatment for patients with poor initial response
      to therapy does not improve outcome. Addition of interferon to treatment for
      patients with favorable initial response does not improve outcome. Addition of
      liposomal muramyl tripeptide to chemotherapy may improve overall survival.
      Systemic therapy for Ewing sarcoma consists of multiagent chemotherapy including
      doxorubicin, vincristine, etoposide, and cyclophosphamide and/or ifosfamide.
      Increased dose intensity of therapy, either by shortening the intervals between
      cycles of chemotherapy or by increasing doses of chemotherapy, improves outcome.
      Regimens such as irinotecan/temozolomide or cyclophosphamide/topotecan have shown
      activity in metastatic recurrent Ewing sarcoma. Trials are ongoing to evaluate
      the addition of these drugs to existing multiagent regimens in order to test
      their ability to improve outcome. High-dose systemic therapy with autologous stem
      cell reconstitution is being tested for patients at high risk for recurrence;
      definitive results await completion of a prospective randomized trial. 

PMID- 25993236
TI  - The biology and management of cartilaginous tumors: a role for targeting
      isocitrate dehydrogenase.
AB  - Chondrosarcomas are rare mesenchymal neoplasms defined by the production of
      abnormal cartilaginous matrix. Conventional chondrosarcoma is the most common
      histology. The management of primary conventional chondrosarcoma generally is
      surgical with the possible addition of radiation therapy. Treatment of
      conventional chondrosarcoma is problematic in unresectable or metastatic disease
      because the tumors tend to be resistant to standard sarcoma chemotherapy
      regimens. Previous attempts at targeted therapy, including inhibitors of Hedgehog
      signaling, the mTOR pathway, and platelet-derived growth factor receptor (PDGFR)
      have been largely disappointing. However, heterozygous mutations in isocitrate
      dehydrogenase (IDH) enzymes recently have been identified in chondrogenic
      neoplasms, with mutations reported in approximately 87% of benign enchondromas,
      70% of conventional chondrosarcomas, and 54% of dedifferentiated chondrosarcomas.
      The normal IDH protein continues to produce alpha-ketoglutarate (alpha-KG)
      whereas the mutant IDH protein converts KG to the oncometabolite 2
      hydroxyglutarate (2-HG). Clinical trials of novel IDH inhibitors are ongoing,
      with evidence of early activity in IDH-mutant leukemias. IDH inhibitors show
      antitumor effects against IDH-mutant chondrosarcoma cell lines, supporting the
      inclusion of patients with chondrosarcoma with IDH mutations on IDH inhibitor
      clinical trials for solid tumors. Targeting IDH mutations may offer hope of a
      novel antineoplastic strategy not only for patients with chondrosarcomas, but
      also for other solid tumors with aberrant IDH activity. 

PMID- 25993237
TI  - Chemotherapy for bone sarcomas in adults: the MD anderson experience.
AB  - Increasing age is an adverse prognostic factor in the treatment of primary bone
      tumors. There are few published data on treatment of primary bone tumors in
      adults. This paper presents data from the Department of Sarcoma Medical Oncology
      at The University of Texas MD Anderson Cancer Center, summarizing our treatment
      results. To treat primary osteosarcoma, we used 90 mg/m2 of doxorubicin as a
      continuous intravenous infusion over 48 to 96 hours and 120 to 160 mg/m2 of
      cisplatin intravenously or intra-arterially. Initially, we found a marked
      difference in postoperative continuous disease-free survival (CDFS) between those
      with 90% or greater (i.e., good response) tumor necrosis and those with less than
      90% (i.e., poor response) tumor necrosis. The sequential addition of high-dose
      methotrexate and ifosfamide to patients with poorly responding disease improved
      their CDFS to that of patients with good response. Older patients and those who
      have tumors with variant histology have inferior outcomes. Evaluation of
      subsequent patients revealed similar outcomes for those with good or poor
      response to induction therapy, supporting our practice of adaptation of
      postoperative chemotherapy to the results of preoperative chemotherapy. PET-CT is
      the best imaging modality to screen for a response with tumors inside bone. To
      treat Ewing sarcoma, we have employed 2 mg of vincristine, 75 to 90 mg/m2 of
      doxorubicin as a 72-hour infusion, and 2.5 g/m2 of ifosfamide over 3 hours daily
      for 4 doses (i.e., vincristine, doxorubicin, and ifosfamide [VAI]). Preliminary
      analysis indicates a higher CDFS when adjusted for patient age than seen with the
      standard alternating regimen used in pediatrics. A screening MRI of the pelvis
      and spine can detect subtle metastatic disease in bone or bone marrow that is
      missed by other imaging modalities or blind biopsy. Chondrosarcoma is treated
      surgically or on investigational protocols. Giant cell tumor of bone is usually
      managed surgically, but multiple options exist for medical treatment, and therapy
      is individualized with embolization, denosumab, and interferon.

PMID- 25993238
TI  - Can diet and lifestyle prevent breast cancer: what is the evidence?
AB  - Breast cancer is the most common cancer among women in both developed and less
      developed countries. Rates of breast cancer are increasing worldwide, with a
      particular increase in postmenopausal and estrogen receptor-positive cases. The
      World Cancer Research Fund (WCRF) and American Cancer Society (ACS) cancer
      prevention guidelines recommend maintaining a healthy weight, undertaking at
      least 150 minutes of moderate intensity exercise per week, limiting alcohol
      consumption, and eating a plant-based diet. Observational data link adherence to
      physical activity and alcohol guidelines throughout life to a reduced risk of
      developing pre- and postmenopausal breast cancer. Weight control throughout life
      appears to prevent cases after menopause. Adherence to a healthy dietary pattern
      does not have specific effects on breast cancer risk but remains important as it
      reduces the risk for other common diseases, such as cardiovascular disease (CVD),
      diabetes, and dementia. Emerging data suggest that smoking during adolescence or
      early adulthood increases later risk of breast cancer. Lifestyle factors appear
      to modify risk among high-risk women with a family history and those with typical
      risk of the general population, although their effects among carriers of BRCA
      mutations are not well defined. Recent expert reports estimate that successful
      lifestyle changes could prevent 25% to 30% of cases of breast cancer. These
      reductions will only be achieved if we can implement targeted prevention programs
      for high-risk women and women in population-based breast screening programs
      during childhood, adolescence, and early adulthood when the rapidly developing
      breast is particularly susceptible to carcinogenesis. 

PMID- 25993239
TI  - Clonal evolution models of tumor heterogeneity.
AB  - Somatic/clonal evolution is the process of sequential acquisition of vertically
      transmittable genetic/epigenetic elements in multicellular organisms. Cancer is
      the result of somatic evolution. Understanding the processes that shape the
      evolution of individual tumors might help us to treat cancer more efficiently.
      The initiating genetic/epigenetic events occur in functional cells and provide
      the cell of origin a selective advantage under a changing environment. The
      initiating genetic events tend to be enriched in specific tissues (and are
      sometimes specific for those tissues), as different tissues undergo different
      changes in the environment that will activate selective forces on different cells
      of origin. For the initial clonal expansion to occur premalignant clones need to
      have a relative fitness advantage over their competitors. It is estimated that
      the premalignant phase can take several years. Once the premalignant clonal
      expansion is established, the premalignant cells will contribute to the changing
      environment and will start competing among themselves. In late stages of cancer
      evolution the environmental changes might be similar across different tissues,
      including a lack of physical space, a shortage of energy, and activation of the
      immune system, and more and more of the hallmarks of cancer will evolve. In this
      review we will explore the possible clinical relevance of the heterogeneity that
      evolves during this long somatic evolution. Above all, it should be stressed that
      the earlier the clonal expansion is recognized, the less diverse and less fit for
      survival the cells in the population are. 

PMID- 25993240
TI  - "Lassie," "Toto," and fellow pet dogs: poised to lead the way for advances in
      cancer prevention.
AB  - Cancer causes substantial morbidity and takes the lives of over 8 million people
      worldwide each year. Advances in cancer prevention research are crucial, and
      animal models are key to this. There are many valuable experimentally induced
      cancer models, but these do not fully meet the needs for cancer prevention
      studies. Pet dogs with risks for naturally occurring cancer can fill important
      gaps in cancer prevention research. Using invasive urothelial carcinoma (iUC) as
      an example, the advantages of utilizing pet dogs include: (1) close similarities
      between dogs and humans in carcinogenesis, molecular and cellular features,
      invasive and metastatic behavior, and response to treatment, thus providing high
      relevance for comparative studies, (2) shared environment between dogs and humans
      to help identify not-yet-known environmental iUC risks, (3) strong breed
      associated risk (5- to 21-fold increased risk compared with mixed breeds) that
      facilitates investigation of gene-environment interactions, screening, and early
      intervention, (4) large size of dogs (versus rodents) that allows collection of
      fluids and tissues via cystoscopy, and detailed imaging at multiple time points,
      and (5) acceptance for studies in which each participating dog can benefit while
      enjoying life in their family environment, and in which findings will help other
      dogs and humans. An ongoing 3-year study in Scottish Terriers (comparable to a 15
      to 20-year study in humans) is aimed at defining genetic and environmental risk
      factors for iUC, effective methods for screening/early detection, and a
      successful secondary cancer prevention approach with very promising results to
      date. Pet dogs can indeed propel cancer prevention research. 

PMID- 25993241
TI  - Reform of the Buy-and-Bill System for Outpatient Chemotherapy Care Is Inevitable:
      Perspectives from an Economist, a Realpolitik, and an Oncologist.
AB  - Treating patients with cancer with infused or injected oncolytics is a core
      component of outpatient oncology practice. Currently, practices purchase drugs
      and then bill insurers, colloquially called "buy and bill." Reimbursement for
      these drugs is the largest source of gross revenue for oncology practices, and as
      the prices of cancer drugs have grown over time, these purchases have had
      significant impact on the financial health of practices and pose a risk that
      jeopardizes the ability of many practices to operate and provide patient care.
      Medicare Part B spending on drugs is under political scrutiny because of federal
      spending pressures, and the margin between buy and bill, lowered to 6% by the
      Medicare Modernization Act and further decreased to 4.3% by sequestration, is a
      convenient and popular target of budgetary discussions and proposals, scored to
      save billions of dollars over 10-year budget windows for each percentage-point
      reduction. Alternatives to the buy-and-bill system have been proposed to include
      invoice pricing, least costly alternative reimbursement, bundling of drugs into
      episode-of-care payments, shifting Part B drugs to the Medicare Part D benefit,
      and revision of the failed Competitive Acquisition Program. This article brings
      the perspectives of policy makers, health care economists, and providers together
      to discuss this major challenge in oncology payment reform. 

PMID- 25993242
TI  - Surgery or ablative radiotherapy for breast cancer oligometastases.
AB  - Precisely focused radiation or surgical resection of limited metastases resulted
      in long-term disease control and survival in multiple studies of patients with
      oligometastatic breast cancer. The integration of these ablative techniques into
      standard systemic therapy regimens has the potential to be paradigm shifting,
      leaving many patients without evidence of disease. Although an attractive
      treatment option, the utility of these therapies have not been proven in
      controlled studies, and improved outcomes may be because of patient selection or
      favorable biology alone. Ongoing studies continue to refine radiation techniques
      and determine the role for ablative therapies in the management of patients with
      metastatic breast cancer (MBC). Additionally, patient selection for metastasis
      directed therapies is based on clinical criteria, with many not benefiting from
      therapies that may have substantial toxicities. Recent reports are beginning to
      uncover the biology of oligometastatic cancer, but much work is needed. Current
      and developing trials that integrate both clinical and translational endpoints
      have the potential to transform management strategies in women with limited MBC. 

PMID- 25993243
TI  - The patient-centered medical home in oncology: from concept to reality.
AB  - In recent years, the cost of providing quality cancer care has been subject to an
      epic escalation causing concerns on the verge of a health care crisis. Innovative
      patient-management models in oncology based on patient-centered medical home
      (PCMH) principles, coupled with alternative payments to traditional fee for
      service (FFS), such as bundled and episodes payment are now showing evidence of
      effectiveness. These efforts have the potential to bend the cost curve while also
      improving quality of care and patient satisfaction. However, going forward with
      FFS alternatives, there are several performance-based payment options with an
      array of financial risks and rewards. Most novel payment options convey a greater
      financial risk and accountability on the provider. Therefore, the oncology
      medical home (OMH) can be a way to mitigate some financial risks by sharing
      savings with the payer through better global care of the patient, proactively
      preventing complications, emergency department (ED) visits, and hospitalizations.
      However, much of the medical home infrastructure that is required to reduced
      total costs of cancer care comes as an added expense to the provider. As best-of
      practice quality standards are being elucidated and refined, we are now at a
      juncture where payers, providers, policymakers, and other stakeholders should
      work in concert to expand and implement the OMH framework into the variety of
      oncology practice environments to better equip them to assimilate into the new
      payment reform configurations of the future. 

PMID- 25993244
TI  - A Strategic Plan for Integrating ICD-10 in Your Practice and Workflow.
AB  - The adoption of the International Classification of Disease (ICD) 10th Revision
      (ICD-10) diagnosis code set in the United States has been legislatively delayed
      several times with the most recent date for implementation set for October 1,
      2015. The transition from ICD-9 to ICD-10 will be a major undertaking that will
      require a substantial amount of planning. In the following article, we outline
      the steps to develop and implement a strategic plan for the transition to the new
      code set, identify training needs throughout the practice, and review the
      challenges and opportunities associated with the transition to ICD-10. 

PMID- 25993245
TI  - Whole-brain radiotherapy and stereotactic radiosurgery in brain metastases: what
      is the evidence?
AB  - The overall local treatment paradigm of brain metastases, which includes whole
      brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), continues to
      evolve. Local therapies play an important role in the management of brain
      metastases. The choice of local therapy depends on factors that involve the
      patient (performance status, expected survival, and age), the prior treatment
      history, and the tumor (type and subtype, number, size, location of metastases,
      and extracranial disease status). Multidisciplinary collaboration is required to
      facilitate an individualized plan to improve the outcome of disease in patients
      with this life-limiting complication. There has been concern about the
      neurocognitive effects of WBRT. A number of approaches that mitigate cognitive
      dysfunction, such as pharmacologic intervention (memantine) or a hippocampal
      sparing strategy, have been studied in a prospective manner with WBRT. Although
      there has been an increase in the use of SRS in the management of brain
      metastases in recent years, WBRT retains an important therapeutic role. 

PMID- 25993246
TI  - Origin of Near-Infrared Absorption for Azulene-Containing Conjugated Polymers
      upon Protonation or Oxidation.
AB  - A series of azulene-containing conjugated polymers were studied to elucidate
      their tunable absorption properties in near-infrared (NIR) regions (i.e., 1.2-2.5
      MUm) upon protonation/oxidation. Density function theory (DFT) revealed that
      protonation-induced intramolecular charge transfer (ICT) in the polymer backbone
      lead to strong NIR absorption. Distinct spectral change was observed when tiny
      amount of peroxide was added to the protonated polymer in trifluoroacetic
      acid/chloroform solution. Electron paramagnetic resonance (EPR) study confirmed
      the presence of radical cation, which results in the occurrence of newly formed
      absorption band after the addition of peroxide. The spectro-electrochemical
      results and DFT study indicate that polarons and polaron pairs were formed during
      p-doping process, and both the chemical oxidation and electrochemical oxidation
      could be facilitated by TFA protonation. This represents the first reported
      mechanisms of NIR absorption under various protonation/oxidation conditions in a
      single polymer system. 

PMID- 25993247
TI  - Security analysis of the unrestricted identity-based aggregate signature scheme.
AB  - Aggregate signatures allow anyone to combine different signatures signed by
      different signers on different messages into a short signature. An ideal
      aggregate signature scheme is an identity-based aggregate signature (IBAS) scheme
      that supports full aggregation since it can reduce the total transmitted data by
      using an identity string as a public key and anyone can freely aggregate
      different signatures. Constructing a secure IBAS scheme that supports full
      aggregation in bilinear maps is an important open problem. Recently, Yuan et al.
      proposed such a scheme and claimed its security in the random oracle model under
      the computational Diffie-Hellman assumption. In this paper, we show that there is
      an efficient forgery on their IBAS scheme and that their security proof has a
      serious flaw. 

PMID- 25993248
TI  - Effect of uniaxial strain on the site occupancy of hydrogen in vanadium from
      density-functional calculations.
AB  - We investigate the influence of uniaxial strain on the site occupancy of hydrogen
      in vanadium, using density functional theory. The site occupancy is found to be
      strongly influenced by the strain state of the lattice. The results provide the
      conceptual framework for the atomistic description of the observed hysteresis in
      the to phase transition in bulk, as well as the preferred octahedral occupancy of
      hydrogen in strained V layers. 

PMID- 25993249
TI  - Presurgical orthopedics by drink plates does not significantly normalize
      deglutition in infants with cleft lip and palate.
AB  - OBJECTIVE: To test the null hypothesis of no significant difference between
      intraoral pressure characteristics in infants with cleft lip and palate (CLP)
      with or without presurgical orthopedic (PSO) plates (groups CLP and CLP-PSO),
      compared with noncleft infants. MATERIALS AND METHODS: Intraoral atmospheric
      pressure assessments were performed on 17 subjects with preoperative CLP (m/f,
      11/6; mean/SD, 4.76/0.92 months) and a matched control group (n = 24; m/f, 15/9;
      mean/SD, 4.88/0.9 months), for 200 seconds, simultaneously at the vestibulum
      (vestibular space [VS]) and at the palate (subpalatal space [SPS]), using a
      prepared pacifier connected to a digital manometer. Areas under the pressure
      curves (AUC), frequencies, durations, and magnitudes of swallowing peaks and
      pressure resting plateaus were compared between trial groups and locations (VS,
      SPS) using a two-factor analysis of variance for repeated measures, Kruskal
      Wallis test, and Mann-Whitney U-test (alpha = .05). RESULTS: The null hypothesis
      was rejected: Globally, there were statistically significant differences in
      intraoral pressure characteristics between groups CLP, CLP-PSO, and control (all
      P < .01), with significantly higher negative pressures (AUC) in the control
      subjects compared with those of CLP or CLP-PSO. There were significant effects by
      the location of pressure recordings (VS, SPS) and their interaction with all
      treatment groups. Differences between noncleft and CLP subjects were more
      pronounced in the VS than in the SPS. There was no significant effect by PSO.
      CONCLUSION: PSO does not improve deviated swallowing characteristics during
      suction in CLP infants.

PMID- 25993250
TI  - Dentoskeletal effects of a temporary skeletal anchorage device-supported rapid
      maxillary expansion appliance (TSADRME): A pilot study.
AB  - OBJECTIVE: To quantitatively evaluate maxillary skeletal expansion using cone
      beam computed tomography (CBCT) images and propose a novel way to quantify the
      dental tipping effects of temporary skeletal anchorage device-supported rapid
      maxillary expansion appliance (TSADRME). MATERIALS AND METHODS: Images from 25
      patients receiving rapid maxillary expansion with incorporated temporary skeletal
      anchorage devices (TSADs) before activation (T1) and after removal (T2) were
      analyzed to detect dentoskeletal changes. RESULTS: A significant increase from T1
      to T2 was found for all linear measurements except buccal maxillary width at the
      canines. The greatest buccal expansion was at the first molar, decreasing
      anteriorly. However, the greatest palatal expansion was at the first premolar.
      All younger subjects (8-16 years old) exhibited less dental tipping and greater
      expansion overall compared with the older subjects. There was great variability
      in dental tipping of first molars (mean = 4.31 degrees ), with some subjects
      demonstrating mild uprighting of these teeth. CONCLUSIONS: The TSADRME appliance
      is an effective, clinically useful device that results in mild molar tipping and
      may positively affect expansion in the area of TSAD placement.

PMID- 25993251
TI  - Evaluation and comparison of root resorption between tooth-borne and tooth-tissue
      borne rapid maxillary expansion appliances: A CBCT study.
AB  - OBJECTIVE: To compare volumetric root resorption after rapid maxillary expansion
      (RME) between tooth-borne and tissue-borne appliances using CBCT. Repair in
      resorption cavities after 6 months of fixed retention was also compared.
      MATERIALS AND METHODS: A sample of 33 subjects were randomly divided into two
      groups: Hyrax (n  = 16) and Haas (n = 17). CBCT scans were taken 6 months before
      expansion, immediately after expansion, and 6 months after fixed retention.
      Mimics Innovation V 16.0 software was used for segmentation and volumetric
      measurement of 198 teeth. Bland-Altman plots, independent samples t test,
      repeated measures analysis of variance, and the Friedman test were used for
      statistical analysis. RESULTS: Differences in root resorption after RME and
      repair after retention were not significant between the hyrax and Haas appliances
      or between male and female. Significant differences were found between
      preexpansion and postexpansion root volumes in the first premolars and molars-
      even in unattached second premolars. When the percentage of root volume loss is
      considered, no significant difference was found between the first premolar,
      second premolar, and first molar. Volumetric changes after 6 months of retention
      were not statistically significant. CONCLUSIONS: More resorption was observed in
      the Hyrax expander group. But it was not statistically significant. Repair was
      observed after 6 months of retention. Heavy RME forces affected premolars and
      molar similarly.

PMID- 25993252
TI  - Electroceuticals for the metabolic syndrome.

PMID- 25993253
TI  - Renin and aldosterone measurements in the management of arterial hypertension.
AB  - Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory
      system of hemodynamics in man, and its derangements have a key role in the
      development and maintenance of arterial hypertension. Classification of the
      hypertensive states according to different patterns of renin and aldosterone
      levels ("RAAS profiling") allows the diagnosis of specific forms of secondary
      hypertension and may identify distinct hemodynamic subsets in essential
      hypertension. In this review, we summarize the application of RAAS profiling for
      the diagnostic assessment of hypertensive patients and discuss how the
      pathophysiological framework provided by RAAS profiling may guide therapeutic
      decision-making, especially in the context of uncontrolled hypertension not
      responding to multi-therapy. 

PMID- 25993254
TI  - Treatment of Patients with Obese Type 2 Diabetes with Tantalus-DIAMOND(r) Gastric
      Electrical Stimulation: Normal Triglycerides Predict Durable Effects for at Least
      3 Years.
AB  - The objectives of the present work are to evaluate long-term benefit of
      nonexcitatory gastric electrical stimulation (GES) by the DIAMOND((r)) device on
      glycemic control and body weight in patients with type 2 diabetes inadequately
      controlled with oral agents and to determine the magnitude of the modulating
      effects of fasting plasma triglyceride (FTG) levels on these effects of GES.
      Sixty one patients with type 2 diabetes [HbA1c > 7.0% (53 mmol/mol) to < 10.5%
      (91 mmol/mol)] were implanted with the DIAMOND((r)) GES device and treated with
      meal-mediated antral electrical stimulation for up to 36 months. The effects of
      baseline HbA1c and FTG on glycemic control, body weight, and systolic blood
      pressure were measured. GES reduced mean HbA1c by 0.9% and body weight by 5.7%.
      The effects were greater in patients with normal fasting plasma triglycerides
      (NTG) as compared to those with hypertriglyceridemia. The mean decrease in HbA1c
      in patients with NTG averaged 1.1% and was durable over 3 years of follow-up.
      ANCOVA indicated that improvement in HbA1c was a function of both baseline FTG
      group (p = 0.02) and HbA1c (p = 0.001) and their interaction (p = 0.01). Marked
      weight loss (>= 10%) was observed in a significant proportion of NTG patients by
      12 months of treatment and persisted through the 3 years. GES improves glycemic
      control and reduces body weight by a triglyceride-dependent mechanism in patients
      with type 2 diabetes inadequately controlled on oral agents. It is postulated
      that this is through a gut-brain interaction that modulates effects on the liver
      and pancreatic islets.

PMID- 25993255
TI  - This Man's Pill.

PMID- 25993256
TI  - Seasonal differences in extinction and colonization drive occupancy dynamics of
      an imperilled amphibian.
AB  - A detailed understanding of the population dynamics of many amphibian species is
      lacking despite concerns about declining amphibian biodiversity and abundance.
      This paper explores temporal patterns of occupancy and underlying extinction and
      colonization dynamics in a regionally imperiled amphibian species, the Northern
      leopard frog (Lithobates pipiens) in Alberta. Our study contributes to
      elucidating regional occupancy dynamics at northern latitudes, where climate
      extremes likely have a profound effect on seasonal occupancy. The primary
      advantage of our study is its wide geographic scale (60,000 km2) and the use of
      repeat visual surveys each spring and summer from 2009-2013. We find that
      occupancy varied more dramatically between seasons than years, with low spring
      and higher summer occupancy. Between spring and summer, colonization was high and
      extinction low; inversely, colonization was low and extinction high over the
      winter. The dynamics of extinction and colonization are complex, making
      conservation management challenging. Our results reveal that Northern leopard
      frog occupancy was constant over the last five years and thus there is no
      evidence of decline or recovery within our study area. Changes to equilibrium
      occupancy are most sensitive to increasing colonization in the spring or
      declining extinction in the summer. Therefore, conservation and management
      efforts should target actions that are likely to increase spring colonization;
      this could be achieved through translocations or improving the quality or access
      to breeding habitat. Because summer occupancy is already high, it may be
      difficult to improve further. Nevertheless, summer extinction could be reduced by
      predator control, increasing water quality or hydroperiod of wetlands, or
      increasing the quality or quantity of summer habitat. 

PMID- 25993257
TI  - Vascular and hepatic impact of short-term intermittent hypoxia in a mouse model
      of metabolic syndrome.
AB  - BACKGROUND: Experimental models of intermittent hypoxia (IH) have been developed
      during the last decade to investigate the consequences of obstructive sleep
      apnea. IH is usually associated with detrimental metabolic and vascular outcomes.
      However, paradoxical protective effects have also been described depending of IH
      patterns and durations applied in studies. We evaluated the impact of short-term
      IH on vascular and metabolic function in a diet-induced model of metabolic
      syndrome (MS). METHODS: Mice were fed either a standard diet or a high fat diet
      (HFD) for 8 weeks. During the final 14 days of each diet, animals were exposed to
      either IH (1 min cycle, FiO2 5% for 30s, FiO2 21% for 30s; 8 h/day) or
      intermittent air (FiO2 21%). Ex-vivo vascular reactivity in response to
      acetylcholine was assessed in aorta rings by myography. Glucose, insulin and
      leptin levels were assessed, as well as serum lipid profile, hepatic
      mitochondrial activity and tissue nitric oxide (NO) release. RESULTS: Mice fed
      with HFD developed moderate markers of dysmetabolism mimicking MS, including
      increased epididymal fat, dyslipidemia, hepatic steatosis and endothelial
      dysfunction. HFD decreased mitochondrial complex I, II and IV activities and
      increased lactate dehydrogenase (LDH) activity in liver. IH applied to HFD mice
      induced a major increase in insulin and leptin levels and prevented endothelial
      dysfunction by restoring NO production. IH also restored mitochondrial complex I
      and IV activities, moderated the increase in LDH activity and liver triglyceride
      accumulation in HFD mice. CONCLUSION: In a mouse model of MS, short-term IH
      increases insulin and leptin levels, restores endothelial function and
      mitochondrial activity and limits liver lipid accumulation.

PMID- 25993258
TI  - Flavonoid Glycosides of Polygonum capitatum Protect against Inflammation
      Associated with Helicobacter pylori Infection.
AB  - The antibacterial and anti-inflammatory activities, and protective effects of
      extracts (flavonoid glycosides) of Polygonum capitatum were investigated to
      detect the evidence for the utilization of the herb in the clinical therapy of
      gastritis caused by H. pylori. A mouse gastritis model was established using H.
      pylori. According to treating methods, model mice were random assigned into a
      model group (MG group), a triple antibiotics group (TG group, clarithromycin,
      omeprazole and amoxicillin), low/middle/high concentrations of flavonoid
      glycosides groups (LF, MF and HF groups) and low/middle/high concentrations of
      flavonoid glycosides and amoxicillin groups (LFA, MFA and HFA groups). A group
      with pathogen-free mice was regarded as a control group (CG group). The eradicate
      rates of H. pylori were 100%, 93%, 89% in TG, MFA and HF groups. The serum levels
      of IFN-gamma and gastrin were higher in a MG group than those from all other
      groups (P < 0.05). The serum levels of IFN-gamma and gastrin were reduced
      significantly in LF, MF and HF groups (P < 0.05) while little changes were
      observed in LFA, MFA and HFA groups. In contrast, the serum levels of IL-4 were
      lower and higher in MG and CG groups compared with other groups (P<0.05). The
      serum levels of IL-4 were increased significantly in LF, MF and HF groups (P <
      0.05) while little changes were found in LFA, MFA and HFA groups. According to
      pathological scores, flavonoid glycosides therapy showed better protection for
      gastric injuries than the combination of flavonoid glycoside and amoxicillin (P <
      0.05). The results suggested that flavonoid glycoside has repairing functions for
      gastric injuries. The results suggest that the plant can treat gastritis and
      protect against gastric injuries. The flavonoid glycosides from Polygonum
      capitatum should be developed as a potential drug for the therapy of gastritis
      caused by H. pylori. 

PMID- 25993259
TI  - Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in
      experimental spinal cord injury.
AB  - Reduced spinal cord blood flow (SCBF) (i.e., ischemia) plays a key role in
      traumatic spinal cord injury (SCI) pathophysiology and is accordingly an
      important target for neuroprotective therapies. Although several techniques have
      been described to assess SCBF, they all have significant limitations. To overcome
      the latter, we propose the use of real-time contrast enhanced ultrasound imaging
      (CEU). Here we describe the application of this technique in a rat contusion
      model of SCI. A jugular catheter is first implanted for the repeated injection of
      contrast agent, a sodium chloride solution of sulphur hexafluoride encapsulated
      microbubbles. The spine is then stabilized with a custom-made 3D-frame and the
      spinal cord dura mater is exposed by a laminectomy at ThIX-ThXII. The ultrasound
      probe is then positioned at the posterior aspect of the dura mater (coated with
      ultrasound gel). To assess baseline SCBF, a single intravenous injection (400 ul)
      of contrast agent is applied to record its passage through the intact spinal cord
      microvasculature. A weight-drop device is subsequently used to generate a
      reproducible experimental contusion model of SCI. Contrast agent is re-injected
      15 min following the injury to assess post-SCI SCBF changes. CEU allows for real
      time and in-vivo assessment of SCBF changes following SCI. In the uninjured
      animal, ultrasound imaging showed uneven blood flow along the intact spinal cord.
      Furthermore, 15 min post-SCI, there was critical ischemia at the level of the
      epicenter while SCBF remained preserved in the more remote intact areas. In the
      regions adjacent to the epicenter (both rostral and caudal), SCBF was
      significantly reduced. This corresponds to the previously described "ischemic
      penumbra zone". This tool is of major interest for assessing the effects of
      therapies aimed at limiting ischemia and the resulting tissue necrosis subsequent
      to SCI. 

PMID- 25993260
TI  - Measuring oxidative stress resistance of Caenorhabditis elegans in 96-well
      microtiter plates.
AB  - Oxidative stress, which is the result of an imbalance between production and
      detoxification of reactive oxygen species, is a major contributor to chronic
      human disorders, including cardiovascular and neurodegenerative diseases,
      diabetes, aging, and cancer. Therefore, it is important to study oxidative stress
      not only in cell systems but also using whole organisms. C. elegans is an
      attractive model organism to study the genetics of oxidative stress signal
      transduction pathways, which are highly evolutionarily conserved. Here, we
      provide a protocol to measure oxidative stress resistance in C. elegans in
      liquid. Briefly, ROS-inducing reagents such as paraquat (PQ) and H2O2 are
      dissolved in M9 buffer, and solutions are aliquoted in the wells of a 96 well
      microtiter plate. Synchronized L4/young adult C. elegans animals are transferred
      to the wells (5-8 animals/well) and survival is measured every hour until most
      worms are dead. When performing an oxidative stress resistance assay using a low
      concentration of stressors in plates, aging might influence the behavior of
      animals upon oxidative stress, which could lead to an incorrect interpretation of
      the data. However, in the assay described herein, this problem is unlikely to
      occur since only L4/young adult animals are being used. Moreover, this protocol
      is inexpensive and results are obtained in one day, which renders this technique
      attractive for genetic screens. Overall, this will help to understand oxidative
      stress signal transduction pathways, which could be translated into better
      characterization of oxidative stress-associated human disorders. 

PMID- 25993261
TI  - Elastomeric and soft conducting microwires for implantable neural interfaces.
AB  - Current designs for microelectrodes used for interfacing with the nervous system
      elicit a characteristic inflammatory response that leads to scar tissue
      encapsulation, electrical insulation of the electrode from the tissue and
      ultimately failure. Traditionally, relatively stiff materials like tungsten and
      silicon are employed which have mechanical properties several orders of magnitude
      different from neural tissue. This mechanical mismatch is thought to be a major
      cause of chronic inflammation and degeneration around the device. In an effort to
      minimize the disparity between neural interface devices and the brain, novel soft
      electrodes consisting of elastomers and intrinsically conducting polymers were
      fabricated. The physical, mechanical and electrochemical properties of these
      materials were extensively characterized to identify the formulations with the
      optimal combination of parameters including Young's modulus, elongation at break,
      ultimate tensile strength, conductivity, impedance and surface charge injection.
      Our final electrode has a Young's modulus of 974 kPa which is five orders of
      magnitude lower than tungsten and significantly lower than other polymer-based
      neural electrode materials. In vitro cell culture experiments demonstrated the
      favorable interaction between these soft materials and neurons, astrocytes and
      microglia, with higher neuronal attachment and a two-fold reduction in
      inflammatory microglia attachment on soft devices compared to stiff controls.
      Surface immobilization of neuronal adhesion proteins on these microwires further
      improved the cellular response. Finally, in vivo electrophysiology demonstrated
      the functionality of the elastomeric electrodes in recording single unit activity
      in the rodent visual cortex. The results presented provide initial evidence in
      support of the use of soft materials in neural interface applications. 

PMID- 25993262
TI  - Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of
      Feature Recognition and Accuracy of Diagnosis.
AB  - IMPORTANCE: Reflectance confocal microscopy (RCM) studies have been performed to
      identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis
      is operator dependent. Hence, reproducibility of RCM criteria needs to be tested.
      OBJECTIVE: To test interobserver reproducibility of recognition of previously
      published RCM descriptors and accuracy of RCM-based skin cancer diagnosis.
      DESIGN, SETTING, AND PARTICIPANTS: Observational retrospective web-based study of
      a set of RCM images collected at a tertiary academic medical center. Nine
      dermatologists (6 of whom had >=3 years of RCM experience) from 6 countries
      evaluated an RCM study set from 100 biopsy-proven lesions, including 55
      melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or
      seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October
      21, 2010, participanting dermatologists, blinded to histopathological diagnosis,
      evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM
      descriptors. MAIN OUTCOMES AND MEASURES: The main outcome was identification of
      RCM descriptors with fair to good interrater agreement (kappa statistic, >=0.3)
      and independent correlation with malignant vs benign diagnosis on discriminant
      analysis. Additional measures included sensitivity and specificity for diagnosis
      of malignant vs benign for each evaluator, for majority diagnosis (rendered by
      >=5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS: Eight RCM
      descriptors showed fair to good reproducibility and were independently associated
      with a specific diagnosis. Of these, the presence of pagetoid cells, atypical
      cells at the dermal-epidermal junction, and irregular epidermal architecture were
      associated with melanoma. Aspecific junctional pattern, basaloid cords, and
      ulceration were associated with basal cell carcinomas. Ringed junctional pattern
      and dermal nests were associated with nevi. The mean sensitivity for the group of
      evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3%
      (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and
      specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users
      (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%). CONCLUSIONS AND
      RELEVANCE: The study highlights key RCM diagnostic criteria for melanoma and
      basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic
      accuracy increases with experience. The higher accuracy of majority diagnosis
      suggests that there is intrinsically more diagnostic information in RCM images
      than is currently used by individual evaluators.

PMID- 25993263
TI  - Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study
      of Left and Right Curve Driving.
AB  - OBJECTIVES: In the brain, the mechanisms of attention to the left and the right
      are known to be different. It is possible that brain activity when driving also
      differs with different horizontal road alignments (left or right curves), but
      little is known about this. We found driver brain activity to be different when
      driving on left and right curves, in an experiment using a large-scale driving
      simulator and functional near-infrared spectroscopy (fNIRS). RESEARCH DESIGN AND
      METHODS: The participants were fifteen healthy adults. We created a course
      simulating an expressway, comprising straight line driving and gentle left and
      right curves, and monitored the participants under driving conditions, in which
      they drove at a constant speed of 100 km/h, and under non-driving conditions, in
      which they simply watched the screen (visual task). Changes in hemoglobin
      concentrations were monitored at 48 channels including the prefrontal cortex, the
      premotor cortex, the primary motor cortex and the parietal cortex. From
      orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we
      calculated changes in cerebral oxygen exchange, reflecting neural activity, and
      statistically compared the resulting values from the right and left curve
      sections. RESULTS: Under driving conditions, there were no sites where cerebral
      oxygen exchange increased significantly more during right curves than during left
      curves (p > 0.05), but cerebral oxygen exchange increased significantly more
      during left curves (p < 0.05) in the right premotor cortex, the right frontal eye
      field and the bilateral prefrontal cortex. Under non-driving conditions,
      increases were significantly greater during left curves (p < 0.05) only in the
      right frontal eye field. CONCLUSIONS: Left curve driving was thus found to
      require more brain activity at multiple sites, suggesting that left curve driving
      may require more visual attention than right curve driving. The right frontal eye
      field was activated under both driving and non-driving conditions.

PMID- 25993264
TI  - Does Generalization Occur Following Computer-Based Cognitive Retraining?-An
      Exploratory Study.
AB  - Computer-based cognitive retraining (CBCR) intervention has gained great
      popularity in recent years. This study aimed to investigate the occurrence of
      skill generalization to daily living task for individuals with acquired brain
      injury (ABI) after completion of eight modules of a commercially available CBCR
      program, the Parrot Software. The study investigated changes in individuals'
      global cognition as measured by the Montreal Cognitive Assessment, and changes in
      individuals' performance during a medication-box sorting task, a novel
      instrumental activity of daily living. The medication-box sorting task resembled
      real life medication management with daily prescribed and over-the-counter
      medications. Twelve individuals with ABI from a community-based program completed
      the study. Results indicated that CBCR intervention brought about improvement in
      global cognition, but the improvement did not appear in any particular cognitive
      domain. Additionally, the gains in global cognition failed to enhance performance
      in the medication-box sorting task. This exploratory study demonstrated that
      while CBCR may be a promising intervention for improving global cognition in
      individuals with ABI, additional intervention might be needed for generalization
      to occur to a novel daily task. Future studies should look for the ultimate
      therapeutic outcome from CBCR interventions or include interventions that could
      bridge the gap between CBCR intervention and performance improvement in daily
      living occupations. 

PMID- 25993265
TI  - High Q-factor microring resonator wrapped by the curved waveguide.
AB  - In this work, we study the performances of ring resonators of different type by
      analyzing the bending loss and the condition of the critical coupling. We propose
      that the bending loss of microring can be reduced by wrapping a concentrically
      curved waveguide. The difference of propagation constant between two
      concentrically curved waveguides can be tuned by adjusting the bus waveguide
      width to optimize the critical coupling. Furthermore, we propose to enlarge the
      difference of the propagation constant between two concentrically curved
      waveguides to maintain the circulating light in the ring to obtain higher quality
      factor. In this study, the highest quality factor that we measured is 7 * 10(5).

PMID- 25993266
TI  - The relevance of pupillometry for evaluation of analgesia before noxious
      procedures in the intensive care unit.
AB  - BACKGROUND: Many patients in the intensive care unit are unable to communicate
      verbally. Accurately predicting whether such patients will exhibit painful
      behaviors during noxious procedures and assessing the adequacy of analgesia
      during those procedures is a challenge. In addition to observational pain
      assessment tools such as the Behavioral Pain Scale, physiologic indicators such
      as the pupillary response have been proposed. The pupil is innervated by both
      divisions of the autonomic nervous system and is affected by pain and analgesic
      medications. We evaluated the pupillary response to a light stimulus before
      noxious procedures as a method to predict pain during the procedure. METHODS: We
      correlated different aspects of the pupillary light reflex with established
      strategies for pain assessment to evaluate the adequacy of analgesia before
      surgical dressing changes performed in the intensive care unit in patients with
      cellulitis associated with mediastinitis or not. RESULTS: We found that a
      percentage of variation in pupil size >19% predicted the presence of pain as
      assessed by a Behavioral Pain Scale score of >3 with a sensitivity of 100% (95%
      confidence interval, 100%-100%) and a specificity of 77% (95% confidence
      interval, 54%-100%). CONCLUSIONS: In patients unable to communicate verbally,
      pupillometry may potentially guide caregivers to adjust analgesia before noxious
      procedures.

PMID- 25993267
TI  - Establishment of a human multiple myeloma xenograft model in the chicken to study
      tumor growth, invasion and angiogenesis.
AB  - Multiple myeloma (MM), a malignant plasma cell disease, remains incurable and
      novel drugs are required to improve the prognosis of patients. Due to the lack of
      the bone microenvironment and auto/paracrine growth factors human MM cells are
      difficult to cultivate. Therefore, there is an urgent need to establish proper in
      vitro and in vivo culture systems to study the action of novel therapeutics on
      human MM cells. Here we present a model to grow human multiple myeloma cells in a
      complex 3D environment in vitro and in vivo. MM cell lines OPM-2 and RPMI-8226
      were transfected to express the transgene GFP and were cultivated in the presence
      of human mesenchymal cells and collagen type-I matrix as three-dimensional
      spheroids. In addition, spheroids were grafted on the chorioallantoic membrane
      (CAM) of chicken embryos and tumor growth was monitored by stereo fluorescence
      microscopy. Both models allow the study of novel therapeutic drugs in a complex
      3D environment and the quantification of the tumor cell mass after homogenization
      of grafts in a transgene-specific GFP-ELISA. Moreover, angiogenic responses of
      the host and invasion of tumor cells into the subjacent host tissue can be
      monitored daily by a stereo microscope and analyzed by immunohistochemical
      staining against human tumor cells (Ki-67, CD138, Vimentin) or host mural cells
      covering blood vessels (desmin/ASMA). In conclusion, the onplant system allows
      studying MM cell growth and angiogenesis in a complex 3D environment and enables
      screening for novel therapeutic compounds targeting survival and proliferation of
      MM cells. 

PMID- 25993268
TI  - Encouragement of Enzyme Reaction Utilizing Heat Generation from Ferromagnetic
      Particles Subjected to an AC Magnetic Field.
AB  - We propose a method of activating an enzyme utilizing heat generation from
      ferromagnetic particles under an ac magnetic field. We immobilize alpha-amylase
      on the surface of ferromagnetic particles and analyze its activity. We find that
      when alpha-amylase/ferromagnetic particle hybrids, that is, ferromagnetic
      particles, on which alpha-amylase molecules are immobilized, are subjected to an
      ac magnetic field, the particles generate heat and as a result, alpha-amylase on
      the particles is heated up and activated. We next prepare a solution, in which
      alpha-amylase/ferromagnetic particle hybrids and free, nonimmobilized chitinase
      are dispersed, and analyze their activities. We find that when the solution is
      subjected to an ac magnetic field, the activity of alpha-amylase immobilized on
      the particles increases, whereas that of free chitinase hardly changes; in other
      words, only alpha-amylase immobilized on the particles is selectively activated
      due to heat generation from the particles. 

PMID- 25993269
TI  - Novel Bioactive Hybrid Compound Dual Targeting Estrogen Receptor and Histone
      Deacetylase for the Treatment of Breast Cancer.
AB  - A strategy to develop chemotherapeutic agents by combining several active groups
      into a single molecule as a conjugate that can modulate multiple cellular
      pathways may produce compounds having higher efficacy compared to that of single
      target drugs. In this article, we describe the synthesis and evaluation of an
      array of dual-acting ER and histone deacetylase inhibitors. These novel hybrid
      compounds combine an indirect antagonism structure motif of ER (OBHS,
      oxabicycloheptene sulfonate) with the HDAC inhibitor suberoylanilide hydroxamic
      acid (SAHA). These OBHS-HDACi conjugates exhibited good ER binding affinity and
      excellent ERalpha antagonistic activity, and they also exhibited potent
      inhibitory activities against HDACs. Compared with the approved drug tamoxifen,
      these conjugates exhibited higher antitumor potency in ERalpha-positive breast
      cancer cells (MCF-7). Moreover, these conjugates not only showed selective
      anticancer activity that was more potent against MCF-7 cells than DU 145
      (prostate cancer), but they had no toxicity toward normal cells. 

PMID- 25993272
TI  - Solid colloids with surface-mobile linkers.
AB  - In this report we review the possibilities of using colloids with surface mobile
      linkers for the study of colloidal self-assembly processes. A promising route to
      create systems with mobile linkers is the use of lipid (bi-)layers. These lipid
      layers can be either used in the form of vesicles or as coatings for hard
      colloids and emulsion droplets. Inside the lipid bilayers molecules can be
      inserted via membrane anchors. Due to the fluidity of the lipid bilayer, the
      anchored molecules remain mobile. The use of different lipid mixtures even allows
      creating Janus-like particles that exhibit directional bonding if linkers are
      used which have a preference for a certain lipid phase. In nature mobile linkers
      can be found e.g. as receptors in cells. Therefore, towards the end of the
      review, we also briefly address the possibility of using colloids with surface
      mobile linkers as model systems to mimic cell-cell interactions and cell adhesion
      processes. 

PMID- 25993270
TI  - Functional and Spectroscopic Characterization of Chlamydomonas reinhardtii
      Truncated Hemoglobins.
AB  - The single-cell green alga Chlamydomonas reinhardtii harbors twelve truncated
      hemoglobins (Cr-TrHbs). Cr-TrHb1-1 and Cr-TrHb1-8 have been postulated to be
      parts of the nitrogen assimilation pathway, and of a NO-dependent signaling
      pathway, respectively. Here, spectroscopic and reactivity properties of Cr-TrHb1
      1, Cr-TrHb1-2, and Cr-TrHb1-4, all belonging to clsss 1 (previously known as
      group N or group I), are reported. The ferric form of Cr-TrHb1-1, Cr-TrHb1-2, and
      Cr-TrHb1-4 displays a stable 6cLS heme-Fe atom, whereas the hexa-coordination of
      the ferrous derivative appears less strongly stabilized. Accordingly, kinetics of
      azide binding to ferric Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are independent of
      the ligand concentration. Conversely, kinetics of CO or NO2- binding to ferrous
      Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are ligand-dependent at low CO or NO2-
      concentrations, tending to level off at high ligand concentrations, suggesting
      the presence of a rate-limiting step. In agreement with the different heme-Fe
      environments, the pH-dependent kinetics for CO and NO2-binding to ferrous Cr
      TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are characterized by different ligand-linked
      protonation events. This raises the question of whether the simultaneous presence
      in C. reinhardtii of multiple TrHb1s may be related to different regulatory
      roles. 

PMID- 25993273
TI  - Ultrafast Lateral Photo-Dember Effect in Graphene Induced by Nonequilibrium Hot
      Carrier Dynamics.
AB  - The photo-Dember effect arises from the asymmetric diffusivity of photoexcited
      electrons and holes, which creates a transient spatial charge distribution and
      hence the buildup of a voltage. Conventionally, a strong photo-Dember effect is
      only observed in semiconductors with a large asymmetry between the electron and
      hole mobilities, such as in GaAs or InAs, and is considered negligible in
      graphene due to its electron-hole symmetry. Here, we report the observation of a
      strong lateral photo-Dember effect induced by nonequilibrium hot carrier dynamics
      when exciting a graphene-metal interface with a femtosecond laser. Scanning
      photocurrent measurements reveal the extraction of photoexcited hot carriers is
      driven by the transient photo-Dember field, and the polarity of the photocurrent
      is determined by the device's mobility asymmetry. Furthermore, ultrafast pump
      probe measurements indicate the magnitude of photocurrent is related to the hot
      carrier cooling rate. Our simulations also suggest that the lateral photo-Dember
      effect originates from graphene's 2D nature combined with its unique electrical
      and optical properties. Taken together, these results not only reveal a new
      ultrafast photocurrent generation mechanism in graphene but also suggest new
      types of terahertz sources based on 2D nanomaterials. 

PMID- 25993271
TI  - Determinants of reduced antiplatelet effect of aspirin in patients with stable
      coronary artery disease.
AB  - BACKGROUND: Aspirin is a cornerstone in management of coronary artery disease
      (CAD). However, considerable variability in the antiplatelet effect of aspirin
      has been reported. AIM: To investigate independent determinants of reduced
      antiplatelet effect of aspirin in stable CAD patients. METHODS: We performed a
      cross-sectional study including 900 stable, high-risk CAD patients. Among these,
      795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170
      (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet
      therapy. The antiplatelet effect of aspirin was assessed by measurement of
      platelet aggregation employing 1) multiple electrode aggregometry (MEA,
      Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using
      arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay.
      Compliance was assessed by measurement of serum thromboxane B2. RESULTS: Platelet
      count, prior myocardial infarction, type 2 diabetes and body mass index were
      independent determinants of increased AA-induced MEA platelet aggregation in
      citrate and hirudin anticoagulated blood (p-values <= 0.045). Similar results
      were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking
      (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent
      determinants of increased platelet aggregation (p-values <= 0.038). Compliance
      was confirmed by low serum thromboxane B2 levels in all patients (median
      [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml). CONCLUSION: Platelet count,
      prior myocardial infarction, type 2 diabetes and body mass index were independent
      determinants of increased platelet aggregation, indicating that these
      characteristics may be key factors in reduced antiplatelet effect of aspirin in
      stable CAD patients.

PMID- 25993274
TI  - The importance of postural cues for determining eye height in immersive virtual
      reality.
AB  - In human perception, the ability to determine eye height is essential, because
      eye height is used to scale heights of objects, velocities, affordances and
      distances, all of which allow for successful environmental interaction. It is
      well understood that eye height is fundamental to determine many of these
      percepts. Yet, how eye height itself is provided is still largely unknown. While
      the information potentially specifying eye height in the real world is naturally
      coincident in an environment with a regular ground surface, these sources of
      information can be easily divergent in similar and common virtual reality
      scenarios. Thus, we conducted virtual reality experiments where we manipulated
      the virtual eye height in a distance perception task to investigate how eye
      height might be determined in such a scenario. We found that humans rely more on
      their postural cues for determining their eye height if there is a conflict
      between visual and postural information and little opportunity for perceptual
      motor calibration is provided. This is demonstrated by the predictable variations
      in their distance estimates. Our results suggest that the eye height in such
      circumstances is informed by postural cues when estimating egocentric distances
      in virtual reality and consequently, does not depend on an internalized value for
      eye height. 

PMID- 25993275
TI  - Clinicopathological characteristics of gynecological cancer associated with
      hypoxia-inducible factor 1alpha expression: a meta-analysis including 6,612
      subjects.
AB  - BACKGROUND: Gynecological cancer is characterized by tumor hypoxia. However, the
      role of hypoxia-inducible factor 1alpha (HIF-1alpha) in gynecological cancer
      remains unclear. METHOD: Electronic databases including Cochrane Library, PUBMED,
      Web of Knowledge and clinical trial registries were searched from inception
      through October 2014 for published, case-control studies assessing the
      association between HIF-1alpha and the clinicopathological characteristics of
      gynecological cancer. We pooled results from 59 studies using fixed or random
      effects models and present results as odds ratios (ORs) following the PRISMA
      guidelines. RESULTS: Our meta-analysis, which included 6,612 women, demonstrated
      that the expression of HIF-1alpha was associated with the clinicopathological
      characteristics of gynecological cancer. The expression of HIF-1alpha in cancer
      or borderline tissue was significantly higher than that in normal tissue (cancer
      vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39,
      p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001;
      cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression
      of HIF-1alpha in III-IV stage or lymph node metastasis was significantly higher
      than that in I-II stage or that without lymph node metastasis, respectively
      (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89,
      p<0.0001). HIF-1alpha was associated with histological grade of cancer (Grade 3
      vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2:
      OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI):
      1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95%
      (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95%
      (CI): 2.48,12.31, p<0.0001). CONCLUSION: HIF-1alpha is associated with the
      malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years
      survival rate and recurrence rate of gynecological cancer. It may play an
      important role in clinical treatment and prognostic evaluation.

PMID- 25993276
TI  - Spawning Dynamics and Size Related Trends in Reproductive Parameters of Southern
      Bluefin Tuna, Thunnus maccoyii.
AB  - Knowledge of spawning behaviour and fecundity of fish is important for estimating
      the reproductive potential of a stock and for constructing appropriate
      statistical models for assessing sustainable catch levels. Estimates of length
      based reproductive parameters are particularly important for determining
      potential annual fecundity as a function of fish size, but they are often
      difficult to estimate reliably. Here we provide new information on the
      reproductive dynamics of southern bluefin tuna (SBT) Thunnus maccoyii through the
      analysis of fish size and ovary histology collected on the spawning ground in
      1993-1995 and 1999-2002. These are used to refine previous parameter estimates of
      spawning dynamics and investigate size related trends in these parameters. Our
      results suggest that the small SBT tend to arrive on the spawning ground slightly
      later and depart earlier in the spawning season relative to large fish. All
      females were mature and the majority were classed as spawning capable (actively
      spawning or non-spawning) with a very small proportion classed as regressing. The
      fraction of females spawning per day decreased with fish size, but once females
      start a spawning episode, they spawned daily irrespective of size. Mean batch
      fecundity was estimated directly at 6.5 million oocytes. Analysis of ovary
      histology and ovary weight data indicated that relative batch fecundity, and the
      duration of spawning and non-spawning episodes, increased with fish size. These
      reproductive parameter estimates could be used with estimates of residency time
      on the spawning ground as a function of fish size (if known) and demographic data
      for the spawning population to provide a time series of relative annual fecundity
      for SBT. 

PMID- 25993277
TI  - Developing and successfully implementing a competency-based portfolio assessment
      system in a postgraduate family medicine residency program.
AB  - The use of portfolios in postgraduate medical residency education to support
      competency development is increasing; however, the processes by which these
      assessment systems are designed, implemented, and maintained are emergent. The
      authors describe the needs assessment, development, implementation, and
      continuing quality improvement processes that have shaped the Portfolio
      Assessment Support System (PASS) used by the postgraduate family medicine program
      at Queen's University since 2009. Their description includes the impetus for
      change and contextual realities that guided the effort, plus the processes used
      for selecting assessment components and developing strategic supports. The
      authors discuss the identification of impact measures at the individual,
      programmatic, and institutional levels and the ways the department uses these to
      monitor how PASS supports competency development, scaffolds residents' self
      regulated learning skills, and promotes professional identity formation. They
      describe the "academic advisor" role and provide an appendix covering the
      portfolio elements. Reflection elements include learning plans, clinical question
      logs, confidence surveys, and reflections about continuity of care and
      significant incidents. Learning module elements cover the required, online
      bioethics, global health, and consult-request modules. Assessment elements cover
      each resident's research project, clinical audits, presentations, objective
      structured clinical exam and simulated office oral exam results, field notes,
      entrustable professional activities, multisource feedback, and in-training
      evaluation reports. Document elements are the resident's continuing medical
      education activities including procedures log, attendance log, and patient
      demographic summaries.The authors wish to support others who are engaged in the
      systematic portfolio-design process or who may adapt aspects of PASS for their
      local programs. 

PMID- 25993279
TI  - Designing evidence-based medicine training to optimize the transfer of skills
      from the classroom to clinical practice: applying the four component
      instructional design model.
AB  - Evidence-based medicine (EBM) skills, although taught in medical schools around
      the world, are not optimally practiced in clinical environments because of
      multiple barriers, including learners' difficulty transferring EBM skills learned
      in the classroom to clinical practice. This lack of skill transfer may be
      partially due to the design of EBM training. To facilitate the transfer of EBM
      skills from the classroom to clinical practice, the authors explore one
      instructional approach, called the Four Component Instructional Design (4C/ID)
      model, to guide the design of EBM training. On the basis of current cognitive
      psychology, including cognitive load theory, the premise of the 4C/ID model is
      that complex skills training, such as EBM training, should include four
      components: learning tasks, supportive information, procedural information, and
      part-task practice. The combination of these four components can inform the
      creation of complex skills training that is designed to avoid overloading
      learners' cognitive abilities; to facilitate the integration of the knowledge,
      skills, and attitudes needed to execute a complex task; and to increase the
      transfer of knowledge to new situations. The authors begin by introducing the
      4C/ID model and describing the benefits of its four components to guide the
      design of EBM training. They include illustrative examples of educational
      practices that are consistent with each component and that can be applied to
      teaching EBM. They conclude by suggesting that medical educators consider
      adopting the 4C/ID model to design, modify, and/or implement EBM training in
      classroom and clinical settings. 

PMID- 25993278
TI  - The Armstrong Institute: An Academic Institute for Patient Safety and Quality
      Improvement, Research, Training, and Practice.
AB  - Academic medical centers (AMCs) could advance the science of health care
      delivery, improve patient safety and quality improvement, and enhance value, but
      many centers have fragmented efforts with little accountability. Johns Hopkins
      Medicine, the AMC under which the Johns Hopkins University School of Medicine and
      the Johns Hopkins Health System are organized, experienced similar challenges,
      with operational patient safety and quality leadership separate from safety and
      quality-related research efforts. To unite efforts and establish accountability,
      the Armstrong Institute for Patient Safety and Quality was created in 2011.The
      authors describe the development, purpose, governance, function, and challenges
      of the institute to help other AMCs replicate it and accelerate safety and
      quality improvement. The purpose is to partner with patients, their loved ones,
      and all interested parties to end preventable harm, continuously improve patient
      outcomes and experience, and eliminate waste in health care. A governance
      structure was created, with care mapped into seven categories, to oversee the
      quality and safety of all patients treated at a Johns Hopkins Medicine entity.
      The governance has a Patient Safety and Quality Board Committee that sets
      strategic goals, and the institute communicates these goals throughout the health
      system and supports personnel in meeting these goals. The institute is organized
      into 13 functional councils reflecting their behaviors and purpose. The institute
      works daily to build the capacity of clinicians trained in safety and quality
      through established programs, advance improvement science, and implement and
      evaluate interventions to improve the quality of care and safety of patients. 

PMID- 25993280
TI  - The Development and Validation of the Interprofessional Attitudes Scale:
      Assessing the Interprofessional Attitudes of Students in the Health Professions.
AB  - PURPOSE: No validated tools assess all four competency domains described in the
      2011 report Core Competencies for Interprofessional Collaborative Practice (IPEC
      Report). The purpose of this study was to develop and validate a tool based on
      the IPEC Report core competency domains that assesses the interprofessional
      attitudes of students in the health professions. METHOD: In 2012, an
      interprofessional team of students and two of the authors developed and
      administered a survey to students from four colleges and schools at the
      University of Utah Health Sciences Center (Health, Medicine, Nursing, and
      Pharmacy). The authors randomly split the responses with complete data into two
      independent subsets: one for exploratory factor analysis (EFA), the other for
      confirmatory factor analysis (CFA). They performed these analyses to validate the
      tool, eliminate redundant questions, and identify subscales. Their analyses
      focused on aligning tool subscales with the IPEC Report core competencies and
      demonstrating good construct validity and internal consistency reliability.
      RESULTS: Of 1,549 students invited, 701 (45.3%) responded. The EFA produced a 27
      item scale, with five subscales: teamwork, roles, and responsibilities; patient
      centeredness; interprofessional biases; diversity and ethics; and community
      centeredness (Cronbach alpha coefficients: 0.62 to 0.92). The CFA indicated that
      the content of the five subscales was consistent with the EFA model. CONCLUSIONS:
      The Interprofessional Attitudes Scale (IPAS) is a novel tool that, compared with
      previous assessment instruments, better reflects current thinking about
      interprofessional competencies. IPAS should prove useful to health sciences
      institutions committed to training students to work collaboratively in
      interprofessional teams.

PMID- 25993281
TI  - Learning across the explicit, implicit, and extra-curricula: an exploratory study
      of the relative proportions of residents' perceived learning in clinical areas at
      three pediatric residency programs.
AB  - PURPOSE: This exploratory multisite study investigated relative proportions of
      residents' perceived learning across the explicit, implicit (typically called
      hidden or informal), and extra-curricula for six Clinical Learning Environment
      Review (CLER) focus areas-patient safety, health care quality, care transitions,
      supervision, fatigue management, and professionalism-using qualitative and
      numeric data. METHOD: In April through June 2013, the authors recruited and
      interviewed third-year categorical pediatric residents from three sites. For each
      CLER focus area, the authors asked residents to think aloud while they assigned a
      total of 60 points to the explicit, implicit, and extra-curricula, according to
      where they perceived their learning occurred. All interviews were audio taped and
      transcribed verbatim. The authors coded qualitative data from interviews using
      the constant comparative method, scrutinized qualitative data for themes, and
      reviewed qualitative and numeric data. RESULTS: A total of 28/79 (35%) residents
      participated. Residents perceived learning to occur most often in the implicit
      curriculum for five of the six CLER focus areas; the one exception being health
      care quality, which predominantly took place in the explicit curriculum. In the
      implicit curriculum, role modeling and "learning by doing" were frequently
      reported modes of learning. The explicit curriculum was perceived as an important
      baseline for understanding clinical areas. Relatively less learning was perceived
      to occur in the extra-curriculum. CONCLUSIONS: The authors believe that
      recognizing learning in "other-than-explicit" curricula could broaden the medical
      education community's understanding of the purview of the medical education
      curriculum and help educators tap into underused educational opportunities for
      important clinical topics.

PMID- 25993282
TI  - Evaluating Academic Scientists Collaborating in Team-Based Research: A Proposed
      Framework.
AB  - Criteria for evaluating faculty are traditionally based on a triad of
      scholarship, teaching, and service. Research scholarship is often measured by
      first or senior authorship on peer-reviewed scientific publications and being
      principal investigator on extramural grants. Yet scientific innovation
      increasingly requires collective rather than individual creativity, which
      traditional measures of achievement were not designed to capture and, thus,
      devalue. The authors propose a simple, flexible framework for evaluating team
      scientists that includes both quantitative and qualitative assessments. An
      approach for documenting contributions of team scientists in team-based
      scholarship, nontraditional education, and specialized service activities is also
      outlined. Although biostatisticians are used for illustration, the approach is
      generalizable to team scientists in other disciplines.The authors offer three key
      recommendations to members of institutional promotion committees, department
      chairs, and others evaluating team scientists. First, contributions to team-based
      scholarship and specialized contributions to education and service need to be
      assessed and given appropriate and substantial weight. Second, evaluations must
      be founded on well-articulated criteria for assessing the stature and
      accomplishments of team scientists. Finally, mechanisms for collecting evaluative
      data must be developed and implemented at the institutional level. Without these
      three essentials, contributions of team scientists will continue to be
      undervalued in the academic environment. 

PMID- 25993283
TI  - The reliability of multisource feedback in competency-based assessment programs:
      the effects of multiple occasions and assessor groups.
AB  - PURPOSE: Residency programs around the world use multisource feedback (MSF) to
      evaluate learners' performance. Studies of the reliability of MSF show mixed
      results. This study aimed to identify the reliability of MSF as practiced across
      occasions with varying numbers of assessors from different professional groups
      (physicians and nonphysicians) and the effect on the reliability of the
      assessment for different competencies when completed by both groups. METHOD: The
      authors collected data from 2008 to 2012 from electronically completed MSF
      questionnaires. In total, 428 residents completed 586 MSF occasions, and 5,020
      assessors provided feedback. The authors used generalizability theory to analyze
      the reliability of MSF for multiple occasions, different competencies, and
      varying numbers of assessors and assessor groups across multiple occasions.
      RESULTS: A reliability coefficient of 0.800 can be achieved with two MSF
      occasions completed by at least 10 assessors per group or with three MSF
      occasions completed by 5 assessors per group. Nonphysicians' scores for the
      "Scholar" and "Health advocate" competencies and physicians' scores for the
      "Health advocate" competency had a negative effect on the composite reliability.
      CONCLUSIONS: A feasible number of assessors per MSF occasion can reliably assess
      residents' performance. Scores from a single occasion should be interpreted
      cautiously. However, every occasion can provide valuable feedback for learning.
      This research confirms that the (unique) characteristics of different assessor
      groups should be considered when interpreting MSF results. Reliability seems to
      be influenced by the included assessor groups and competencies. These findings
      will enhance the utility of MSF during residency training.

PMID- 25993284
TI  - Cost-effectiveness of proton beam therapy for intraocular melanoma.
AB  - PURPOSE: Proton beam therapy is a commonly accepted treatment for intraocular
      melanomas, but the literature is lacking in descriptions of patient preferences
      of clinical outcomes and economic impact. In addition, no economic evaluations
      have been published regarding the incremental cost-effectiveness of proton beam
      therapy compared with enucleation or plaque brachytherapy, typical alternative
      treatments. We, therefore, conducted a cost-utility analysis of these three
      approaches for the treatment of intraocular melanomas. MATERIALS AND METHODS: A
      Markov model was constructed. Model parameters were identified from the published
      literature and publicly available data sources. Cost-effectiveness of each
      treatment was calculated in 2011 US Dollars per quality-adjusted life-year.
      Incremental cost-effectiveness ratios were calculated assuming enucleation as
      reference. One-way sensitivity analyses were conducted on all model parameters. A
      decision threshold of $50,000/quality-adjusted life-year was used to determine
      cost-effectiveness. RESULTS: Enucleation had the lowest costs and quality
      adjusted life-years, and plaque brachytherapy had the highest costs and quality
      adjusted life-years. Compared with enucleation, the base-case incremental cost
      effectiveness ratios for plaque brachytherapy and proton beam therapy were
      $77,500/quality-adjusted life-year and $106,100/quality-adjusted life-year,
      respectively. Results were highly sensitive to multiple parameters. All three
      treatments were considered optimal, and even dominant, depending on the values
      used for sensitive parameters. CONCLUSION: Base-case analysis results suggest
      enucleation to be optimal. However, the optimal choice was not robust to
      sensitivity analyses and, depending on the assumption, both plaque brachytherapy
      and proton beam therapy could be considered cost-effective. Future clinical
      studies should focus on generating further evidence with the greatest parameter
      uncertainty to inform future cost-effectiveness analyses.

PMID- 25993285
TI  - Reanalysis of Wupus agilis (Early Cretaceous) of Chongqing, China as a Large
      Avian Trace: Differentiating between Large Bird and Small Non-Avian Theropod
      Tracks.
AB  - Trace fossils provide the only records of Early Cretaceous birds from many parts
      of the world. The identification of traces from large avian track-makers is made
      difficult given their overall similarity in size and tridactyly in comparison
      with traces of small non-avian theropods. Reanalysis of Wupus agilis from the
      Early Cretaceous (Aptian-Albian) Jiaguan Formation, one of a small but growing
      number of known avian-pterosaur track assemblages, of southeast China determines
      that these are the traces of a large avian track-maker, analogous to extant
      herons. Wupus, originally identified as the trace of a small non-avian theropod
      track-maker, is therefore similar in both footprint and trackway characteristics
      to the Early Cretaceous (Albian) large avian trace Limiavipes curriei from
      western Canada, and Wupus is reassigned to the ichnofamily Limiavipedidae. The
      reanalysis of Wupus reveals that it and Limiavipes are distinct from similar
      traces of small to medium-sized non-avian theropods (Irenichnites,
      Columbosauripus, Magnoavipes) based on their relatively large footprint length to
      pace length ratio and higher mean footprint splay, and that Wupus shares enough
      characters with Limiavipes to be reassigned to the ichnofamily Limiavipedidae.
      The ability to discern traces of large avians from those of small non-avian
      theropods provides more data on the diversity of Early Cretaceous birds. This
      analysis reveals that, despite the current lack of body fossils, large wading
      birds were globally distributed in both Laurasia and Gondwana during the Early
      Cretaceous. 

PMID- 25993286
TI  - Effect of Polyethylene Glycol on the Formation of Magnetic Nanoparticles
      Synthesized by Magnetospirillum magnetotacticum MS-1.
AB  - Magnetotactic bacteria (MTB) synthesize intracellular magnetic nanocrystals
      called magnetosomes, which are composed of either magnetite (Fe3O4) or greigite
      (Fe3S4) and covered with lipid membranes. The production of magnetosomes is
      achieved by the biomineralization process with strict control over the formation
      of magnetosome membrane vesicles, uptake and transport of iron ions, and
      synthesis of mature crystals. These magnetosomes have high potential for both
      biotechnological and nanotechnological applications, but it is still extremely
      difficult to grow MTB and produce a large amount of magnetosomes under the
      conventional cultural conditions. Here, we investigate as a first attempt the
      effect of polyethylene glycol (PEG) added to the culture medium on the increase
      in the yield of magnetosomes formed in Magnetospirillum magnetotacticum MS-1. We
      find that the yield of the formation of magnetosomes can be increased up to
      approximately 130 % by adding PEG200 to the culture medium. We also measure the
      magnetization of the magnetosomes and find that the magnetosomes possess soft
      ferromagnetic characteristics and the saturation mass magnetization is increased
      by 7 %. 

PMID- 25993287
TI  - Hepatitis B Virus X Protein Sensitizes TRAIL-Induced Hepatocyte Apoptosis by
      Inhibiting the E3 Ubiquitin Ligase A20.
AB  - Hepatitis B virus (HBV) infection causes hepatocyte death and liver damage, which
      may eventually lead to cirrhosis and liver cancer. Hepatitis B virus X protein
      (HBx) is a key antigen that is critically involved in HBV-associated liver
      diseases. However, the molecular basis for its pathogenesis, particularly in
      liver damage, has not been well defined. Herein, we report that HBx was able to
      enhance the susceptibility of hepatocytes to TNF-related apoptosis-inducing
      ligand (TRAIL)-induced apoptosis. Increased sensitivity to TRAIL was associated
      with HBx-induced upregulation of miR-125a, which, in turn, suppressed the
      expression of its putative target gene, A20 E3 ligase. Importantly, we
      demonstrate that the defective expression of A20 impaired the K63-linked
      polyubiquitination of caspase-8, which reciprocally enhanced the activation of
      caspase-8, the recruitment of Fas-associated death domain (FADD), and the
      formation of death-inducing signaling complex (DISC), thereby promoting HBx
      mediated apoptotic signaling. Accordingly, antagonizing miR-125a or ectopically
      expressing A20 in hepatocytes abolished the pro-apoptotic effect of HBx.
      Conversely, the overexpression of miR-125a or knockdown of A20 mimicked HBx to
      enhance TRAIL susceptibility in hepatocytes. Thus, we establish, for the first
      time, a miR-125a/A20-initiated and caspase-8-targeted mechanism by which HBx
      modulates apoptotic signaling and increases hepatic susceptibility to the
      damaging agent, which might provide novel insight into HBV-related liver
      pathology. 

PMID- 25993290
TI  - Clonal expansion of T cells in abdominal aortic aneurysm: a role for doxycycline
      as drug of choice?
AB  - Most reported studies with animal models of abdominal aortic aneurysm (AAA) and
      several studies with patients have suggested that doxycycline favourably modifies
      AAA; however, a recent large long-term clinical trial found that doxycycline did
      not limit aneurysm growth. Thus, there is currently no convincing evidence that
      doxycycline reduces AAA expansion. Here, we critically review the available
      experimental and clinical information about the effects of doxycycline when used
      as a pharmacological treatment for AAA. The view that AAA can be considered an
      autoimmune disease and the observation that AAA tissue shows clonal expansion of
      T cells is placed in the light of the well-known inhibition of mitochondrial
      protein synthesis by doxycycline. In T cell leukaemia animal models, this
      inhibitory effect of the antibiotic has been shown to impede T cell
      proliferation, resulting in complete tumour eradication. We suggest that the
      available evidence of doxycycline action on AAA is erroneously ascribed to its
      inhibition of matrix metalloproteinases (MMPs) by competitive binding of the zinc
      ion co-factor. Although competitive binding may explain the inhibition of
      proteolytic activity, it does not explain the observed decreases of MMP mRNA
      levels. We propose that the observed effects of doxycycline are secondary to
      inhibition of mitochondrial protein synthesis. Provided that serum doxycycline
      levels are kept at adequate levels, the inhibition will result in a proliferation
      arrest, especially of clonally expanding T cells. This, in turn, leads to the
      decrease of proinflammatory cytokines that are normally generated by these cells.
      The drastic change in cell type composition may explain the changes in MMP mRNA
      and protein levels in the tissue samples. 

PMID- 25993291
TI  - Immunohistochemical analysis of the natural killer cell cytotoxicity pathway in
      human abdominal aortic aneurysms.
AB  - Our previous analysis using genome-wide microarray expression data revealed
      extreme overrepresentation of immune related genes belonging the Natural Killer
      (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic
      aneurysm (AAA). We followed up the microarray studies by immunohistochemical
      analyses using antibodies against nine members of the NK pathway (VAV1, VAV3,
      PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from
      AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and
      ethnicity-matched donors from autopsies. The results confirmed the microarray
      results. Two different members of the NK pathway, HCST and GRZB, which act at
      different steps in the NK-pathway, were actively transcribed and translated into
      proteins in the same cells in the AAA tissue demonstrated by double staining.
      Furthermore, double staining with antibodies against CD68 or CD8 together with
      HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed
      proteins of the NK-pathway but were not the only inflammatory cells involved in
      the NK-pathway in the AAA tissue. The results provide strong evidence that the NK
      Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight
      for future studies to dissect the pathogenesis of human AAA. 

PMID- 25993289
TI  - Imaging of small animal peripheral artery disease models: recent advancements and
      translational potential.
AB  - Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms
      of arterial disease outside of the heart. As such, PAD development is a
      multifactorial process with a variety of manifestations. For example, aneurysms
      are pathological expansions of an artery that can lead to rupture, while ischemic
      atherosclerosis reduces blood flow, increasing the risk of claudication, poor
      wound healing, limb amputation, and stroke. Current PAD treatment is often
      ineffective or associated with serious risks, largely because these disorders are
      commonly undiagnosed or misdiagnosed. Active areas of research are focused on
      detecting and characterizing deleterious arterial changes at early stages using
      non-invasive imaging strategies, such as ultrasound, as well as emerging
      technologies like photoacoustic imaging. Earlier disease detection and
      characterization could improve interventional strategies, leading to better
      prognosis in PAD patients. While rodents are being used to investigate PAD
      pathophysiology, imaging of these animal models has been underutilized. This
      review focuses on structural and molecular information and disease progression
      revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular
      disease models in mice, rats, and rabbits. Effective translation to humans
      involves better understanding of underlying PAD pathophysiology to develop novel
      therapeutics and apply non-invasive imaging techniques in the clinic. 

PMID- 25993292
TI  - Inhibitory effect of statins on inflammation-related pathways in human abdominal
      aortic aneurysm tissue.
AB  - HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins)
      have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However,
      the effects of statins in human AAA tissues are not fully elucidated. The aim of
      this study was to investigate the direct effects of statins on proinflammatory
      molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited
      the activation of nuclear factor (NF)-kappaB induced by tumor necrosis factor
      (TNF)-alpha in human AAA walls, but showed little effect on c-jun N-terminal
      kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly
      reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte
      chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide
      (CXCL5) under both basal and TNF-alpha-stimulated conditions. Similar to statins,
      the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-kappaB,
      accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the
      effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting
      the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins
      preferentially inhibit the Rac1/NF-kappaB pathway to suppress MMP-9 and chemokine
      secretion in human AAA, suggesting a mechanism for the potential effect of
      statins in attenuating AAA progression. 

PMID- 25993293
TI  - Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human
      Abdominal Aortic Aneurysm.
AB  - We investigated transcriptional control of gene expression in human abdominal
      aortic aneurysm (AAA). We previously identified 3274 differentially expressed
      genes in human AAA tissue compared to non-aneurysmal controls. Four expressed
      transcription factors (ELF1, ETS2, STAT5 and RUNX1) were selected for genome-wide
      chromatin immunoprecipitation. Transcription factor binding was enriched in 4760
      distinct genes (FDR < 0.05), of which 713 were differentially expressed in AAA.
      Functional classification using Gene Ontology (GO), KEGG, and Network Analysis
      revealed enrichment in several biological processes including "leukocyte
      migration" (FDR = 3.09 * 10-05) and "intracellular protein kinase cascade" (FDR =
      6.48 * 10-05). In the control aorta, the most significant GO categories differed
      from those in the AAA samples and included "cytoskeleton organization" (FDR =
      1.24 * 10-06) and "small GTPase mediated signal transduction" (FDR = 1.24 * 10
      06). Genes up-regulated in AAA tissue showed a highly significant enrichment for
      GO categories "leukocyte migration" (FDR = 1.62 * 10-11), "activation of immune
      response" (FDR = 8.44 * 10-11), "T cell activation" (FDR = 4.14 * 10-10) and
      "regulation of lymphocyte activation" (FDR = 2.45 * 10-09), whereas the down
      regulated genes were enriched in GO categories "cytoskeleton organization" (FDR =
      7.84 * 10-05), "muscle cell development" (FDR = 1.00 * 10-04), and "organ
      morphogenesis" (FDR = 3.00 * 10-04). Quantitative PCR assays confirmed a sub-set
      of the transcription factor binding sites including those in MTMR11, DUSP10,
      ITGAM, MARCH1, HDAC8, MMP14, MAGI1, THBD and SPOCK1. 

PMID- 25993294
TI  - The potential role of DNA methylation in abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant
      impact on the aging population. While both genetic and environmental risk factors
      have been implicated in AAA formation, the precise genetic markers involved and
      the factors influencing their expression remain an area of ongoing investigation.
      DNA methylation has been previously used to study gene silencing in other
      inflammatory disorders and since AAA has an extensive inflammatory component, we
      sought to examine the genome-wide DNA methylation profiles in mononuclear blood
      cells of AAA cases and matched non-AAA controls. To this end, we collected blood
      samples and isolated mononuclear cells for DNA and RNA extraction from four all
      male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n =
      10) and control non-smokers (n = 11). Methylation data were obtained using the
      Illumina 450k Human Methylation Bead Chip and analyzed using the R language and
      multiple Bioconductor packages. Principal component analysis and linear analysis
      of CpG island subsets identified four regions with significant differences in
      methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2
      (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and
      adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR
      and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest
      DNA methylation may play a role in AAA pathobiology. 

PMID- 25993295
TI  - Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers
      for Abdominal Aortic Aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked
      changes in the cellular composition of the aortic wall. This study aims to
      identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by
      laser microdissection from human tissue samples. The distribution of inflammatory
      cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA
      biopsies. We observed in half of the samples that adventitial tertiary lymphoid
      organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the
      adventitia. Out of the 850 miRNA that were screened by microarray in isolated
      ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p,
      miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and
      their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and
      M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR
      30a-5p, a similar modulation was found in ATLOs and the two subtypes of
      macrophages. The modulated miRNAs were then evaluated in the plasma of AAA
      patients for their potential as AAA biomarkers. Our data emphasize the potential
      of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO
      evolution. Further investigations will be required to evaluate their targets in
      order to better understand AAA pathophysiology. 

PMID- 25993296
TI  - A review of the pathophysiology and potential biomarkers for peripheral artery
      disease.
AB  - Peripheral artery disease (PAD) is due to the blockage of the arteries supplying
      blood to the lower limbs usually secondary to atherosclerosis. The most severe
      clinical manifestation of PAD is critical limb ischemia (CLI), which is
      associated with a risk of limb loss and mortality due to cardiovascular events.
      Currently CLI is mainly treated by surgical or endovascular revascularization,
      with few other treatments in routine clinical practice. There are a number of
      problems with current PAD management strategies, such as the difficulty in
      selecting the appropriate treatments for individual patients. Many patients
      undergo repeated attempts at revascularization surgery, but ultimately require an
      amputation. There is great interest in developing new methods to identify
      patients who are unlikely to benefit from revascularization and to improve
      management of patients unsuitable for surgery. Circulating biomarkers that
      predict the progression of PAD and the response to therapies could assist in the
      management of patients. This review provides an overview of the pathophysiology
      of PAD and examines the association between circulating biomarkers and PAD
      presence, severity and prognosis. While some currently identified circulating
      markers show promise, further larger studies focused on the clinical value of the
      biomarkers over existing risk predictors are needed. 

PMID- 25993297
TI  - Immunohistochemical analysis of paraoxonases and chemokines in arteries of
      patients with peripheral artery disease.
AB  - Oxidative damage to lipids and lipoproteins is implicated in the development of
      atherosclerotic vascular diseases, including peripheral artery disease (PAD). The
      paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and
      PON3 that protect lipoproteins and cells from peroxidation and, as such, may be
      involved in protection against the atherosclerosis process. PON1 inhibits the
      production of chemokine (C-C motif) ligand 2 (CCL2) in endothelial cells
      incubated with oxidized lipoproteins. PON1 and CCL2 are ubiquitously distributed
      in tissues, and this suggests a joint localization and combined systemic effect.
      The aim of the present study has been to analyze the quantitative
      immunohistochemical localization of PON1, PON3, CCL2 and CCL2 receptors in a
      series of patients with severe PAD. Portions of femoral and/or popliteal arteries
      from 66 patients with PAD were obtained during surgical procedures for infra
      inguinal limb revascularization. We used eight normal arteries from donors as
      controls. PON1 and PON3, CCL2 and the chemokine-binding protein 2, and Duffy
      antigen/chemokine receptor, were increased in PAD patients. There were no
      significant changes in C-C chemokine receptor type 2. Our findings suggest that
      paraoxonases and chemokines play an important role in the development and
      progression of atherosclerosis in peripheral artery disease. 

PMID- 25993298
TI  - Influence of regular exercise on body fat and eating patterns of patients with
      intermittent claudication.
AB  - This study examined the impact of regular supervised exercise on body fat,
      assessed via anthropometry, and eating patterns of peripheral arterial disease
      patients with intermittent claudication (IC). Body fat, eating patterns and
      walking ability were assessed in 11 healthy adults (Control) and age- and mass
      matched IC patients undertaking usual care (n = 10; IC-Con) or supervised
      exercise (12-months; n = 10; IC-Ex). At entry, all groups exhibited similar body
      fat and eating patterns. Maximal walking ability was greatest for Control
      participants and similar for IC-Ex and IC-Con patients. Supervised exercise
      resulted in significantly greater improvements in maximal walking ability (IC-Ex
      148%-170% vs. IC-Con 29%-52%) and smaller increases in body fat (IC-Ex -2.1%-1.4%
      vs. IC-Con 8.4%-10%). IC-Con patients exhibited significantly greater increases
      in body fat compared with Control at follow-up (8.4%-10% vs. -0.6%-1.4%). Eating
      patterns were similar for all groups at follow-up. The current study demonstrated
      that regular, supervised exercise significantly improved maximal walking ability
      and minimised increase in body fat amongst IC patients without changes in eating
      patterns. The study supports the use of supervised exercise to minimize
      cardiovascular risk amongst IC patients. Further studies are needed to examine
      the additional value of other lifestyle interventions such as diet modification. 

PMID- 25993299
TI  - Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after
      Revascularization for Peripheral Arterial Disease.
AB  - Improvement in quality of life (QoL) is a primary treatment goal for patients
      with peripheral arterial disease (PAD). The current study aimed to quantify
      improvement in the health status of PAD patients following peripheral
      revascularization using the peripheral artery questionnaire (PAQ) and ankle
      brachial index (ABI), and to evaluate possible correlation between the two
      methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before,
      and three months after peripheral revascularization. Mean PAQ summary scores
      improved significantly three months after revascularization (+49.3 +/- 15 points,
      p < 0.001). PAQ scores relating to patient symptoms showed the largest
      improvement following revascularization. The smallest increases were seen in
      reported treatment satisfaction (all p's < 0.001). As expected the ABI of treated
      limbs showed significant improvement post-revascularization (p < 0.001). ABI
      after revascularization correlated with patient-reported changes in the physical
      function and QoL domains of the PAQ. Twenty-two percent of PAD patients were
      identified as having a poor response to revascularization (increase in ABI <
      0.15). Interestingly, poor responders reported improvement in symptoms on the
      PAQ, although this was less marked than in patients with an increase in ABI >
      0.15 following revascularization. In conclusion, data from the current study
      suggest a significant correlation between improvement in patient-reported
      outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing
      peripheral revascularization. 

PMID- 25993300
TI  - Statin, calcium channel blocker and Beta blocker therapy may decrease the
      incidence of tuberculosis infection in elderly Taiwanese patients with type 2
      diabetes.
AB  - BACKGROUND: It is well known that diabetes mellitus impairs immunity and
      therefore is an independent risk factor for tuberculosis. However, the influence
      of associated metabolic factors, such as hypertension, dyslipidemia and gout has
      yet to be confirmed. This study aimed to investigate whether the strong
      association between tuberculosis and diabetes mellitus is independent from the
      influence of hypertension and dyslipidemia, and its treatment in elderly
      Taiwanese patients. METHODS: A total of 27,958 patients aged more than 65 years
      were identified from the National Health Insurance Research Database (NIHRD) in
      1997 and were followed from 1998 to 2009. The demographic characteristics between
      the patients with and without diabetes were analyzed using the chi2 test. A total
      of 13,981 patients with type 2 diabetes were included in this study. Cox
      proportional hazard regression models were used to determine the independent
      effects of diabetes on the risk of tuberculosis. RESULTS: After adjusting for
      age, sex, other co-morbidities and medications, calcium channel blocker, beta
      blocker and statin users had a lower independent association, with risk ratios of
      0.76 (95% CI, 0.58-0.98), 0.72 (95% CI, 0.58-0.91) and 0.76 (95% CI, 0.60-0.97),
      respectively. CONCLUSION: Calcium channel blocker, beta blocker and statin
      therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese
      patients with type 2 diabetes.

PMID- 25993301
TI  - Polymorphisms of the Ovine BMPR-IB, BMP-15 and FSHR and Their Associations with
      Litter Size in Two Chinese Indigenous Sheep Breeds.
AB  - The Small Tailed Han sheep and Hu sheep are two prolific local sheep in China. In
      this study, the polymorphisms of BMPR-IB (Bone morphogenetic protein receptor
      IB), BMP-15 (Bone morphogenetic protein 15) and FSHR (follicle stimulating
      hormone receptor) were investigated to check whether they are associated with
      litter size in Small Tailed Han sheep and Hu sheep. Consequently, three
      polymorphisms, FecB mutation in BMPR-IB (c.746A>G), FecG mutation in BMP-15
      (c.718C>T) and the mutation (g. 47C>T) in FSHR were found in the above two sheep
      breeds with a total number of 1630 individuals. The single marker association
      analysis showed that the three mutations were significantly associated with
      litter size. The ewes with genotype FecBB/FecBB and FecBB/FecB+ had 0.78 and 0.58
      more lambs (p < 0.01) than those with genotype FecB+/FecB+, respectively. The
      heterozygous Han and Hu ewes with FecXG/FecX+ genotype showed 0.30 (p = 0.05)
      more lambs than those with the FecX+/FecX+ genotype. For FSHR gene, the ewes with
      genotype CC had 0.52 (p < 0.01) and 0.75 (p < 0.01) more lambs than those with
      genotypes TC and TT, respectively. Combined effect analyses indicated an
      extremely significant interaction (p < 0.01) between the random combinations of
      BMPR-IB, BMP-15 and FSHR genes on litter size. In addition, the Han and Hu ewes
      with BB/G+/CC genotype harbor the highest litter size among ewes analyzed in
      current study. In conclusion, BMPR-IB, BMP-15 and FSHR polymorphisms could be
      used as genetic markers in multi-gene pyramiding for improving litter size in
      sheep husbandry. 

PMID- 25993302
TI  - Comparative Analysis of Anther Transcriptome Profiles of Two Different Rice Male
      Sterile Lines Genotypes under Cold Stress.
AB  - Rice is highly sensitive to cold stress during reproductive developmental stages,
      and little is known about the mechanisms of cold responses in rice anther. Using
      the HiSeqTM 2000 sequencing platform, the anther transcriptome of photo thermo
      sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei'ai64S) were
      analyzed at the fertility sensitive stage under cold stress. Approximately 243
      million clean reads were obtained from four libraries and aligned against the
      oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were
      identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs.
      Functional classification of DEGs was also carried out. The DEGs common to both
      genotypes were mainly involved in signal transduction, metabolism, transport, and
      transcriptional regulation. Most of the DEGs were unique for each comparison
      group. We observed that there were more differentially expressed MYB
      (Myeloblastosis) and zinc finger family transcription factors and signal
      transduction components such as calmodulin/calcium dependent protein kinases in
      the Y58S comparison group. It was also found that ribosome-related DEGs may play
      key roles in cold stress signal transduction. These results presented here would
      be particularly useful for further studies on investigating the molecular
      mechanisms of rice responses to cold stress. 

PMID- 25993303
TI  - Identification and Expression Analysis of Candidate Genes Associated with Defense
      Responses to Phytophthora capsici in Pepper Line "PI 201234".
AB  - Phytophthora capsici (Leonian), classified as an oomycete, seriously threatens
      the production of pepper (Capsicum annuum). Current understanding of the defense
      responses in pepper to P. capsici is limited. In this study, RNA-sequencing
      analysis was utilized to identify differentially expressed genes in the resistant
      line "PI 201234", with 1220 differentially expressed genes detected. Of those
      genes, 480 were up-regulated and 740 were down-regulated, with 211 candidate
      genes found to be involved in defense responses based on the gene annotations.
      Furthermore, the expression patterns of 12 candidate genes were further validated
      via quantitative real-time PCR (qPCR). These genes were found to be significantly
      up-regulated at different time points post-inoculation (6 hpi, 24 hpi, and 5 dpi)
      in the resistant line "PI 201234" and susceptible line "Qiemen". Seven genes were
      found to be involved in cell wall modification, phytoalexin biosynthesis, symptom
      development, and phytohormone signaling pathways, thus possibly playing important
      roles in combating exogenous pathogens. The genes identified herein will provide
      a basis for further gene cloning and functional verification studies and will aid
      in an understanding of the regulatory mechanism of pepper resistance to P.
      capsici. 

PMID- 25993304
TI  - Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through
      Upregulation of CCL2.
AB  - Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain
      metastasis. Although preventing SCLC metastasis to the brain is immensely
      important for survival, the molecular mechanisms of SCLC cells penetrating the
      blood-brain barrier (BBB) are largely unknown. Recently, visfatin has been
      considered as a novel pro-inflammatory adipocytokine involved in various cancers.
      Herein, we present evidence that elevated levels of visfatin in the serum of SCLC
      patients were associated with brain metastasis, and visfain was increased in NCI
      H446 cells, a SCLC cell line, during interacting with human brain microvascular
      endothelial cells (HBMEC). Using in vitro BBB model, we found that visfatin could
      promote NCI-H446 cells migration across HBMEC monolayer, while the effect was
      inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC
      chemokine ligand 2 (CCL2) was involved in visfatin-mediated NCI-H446 cells
      transendothelial migtation. Results also showed that the upregulation of CCL2 in
      the co-culture system was reversed by blockade of visfatin. In particular,
      visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling
      in NCI-H446 cells. Taken together, we demonstrated that visfatin was a
      prospective target for SCLC metastasis to brain, and understanding the molecular
      mediators would lead to effective strategies for inhibition of SCLC brain
      metastasis. 

PMID- 25993305
TI  - MALDI-Mass Spectrometric Imaging Revealing Hypoxia-Driven Lipids and Proteins in
      a Breast Tumor Model.
AB  - Hypoxic areas are a common feature of rapidly growing malignant tumors and their
      metastases and are typically spatially heterogeneous. Hypoxia has a strong impact
      on tumor cell biology and contributes to tumor progression in multiple ways. To
      date, only a few molecular key players in tumor hypoxia, such as hypoxia
      inducible factor-1 (HIF-1), have been discovered. The distribution of
      biomolecules is frequently heterogeneous in the tumor volume and may be driven by
      hypoxia and HIF-1alpha. Understanding the spatially heterogeneous hypoxic
      response of tumors is critical. Mass spectrometric imaging (MSI) provides a
      unique way of imaging biomolecular distributions in tissue sections with high
      spectral and spatial resolution. In this paper, breast tumor xenografts grown
      from MDA-MB-231-HRE-tdTomato cells, with a red fluorescent tdTomato protein
      construct under the control of a hypoxia response element (HRE)-containing
      promoter driven by HIF-1alpha, were used to detect the spatial distribution of
      hypoxic regions. We elucidated the 3D spatial relationship between hypoxic
      regions and the localization of lipids and proteins by using principal component
      analysis-linear discriminant analysis (PCA-LDA) on 3D rendered MSI volume data
      from MDA-MB-231-HRE-tdTomato breast tumor xenografts. In this study, we
      identified hypoxia-regulated proteins active in several distinct pathways such as
      glucose metabolism, regulation of actin cytoskeleton, protein folding,
      translation/ribosome, splicesome, the PI3K-Akt signaling pathway, hemoglobin
      chaperone, protein processing in endoplasmic reticulum, detoxification of
      reactive oxygen species, aurora B signaling/apoptotic execution phase, the RAS
      signaling pathway, the FAS signaling pathway/caspase cascade in apoptosis, and
      telomere stress induced senescence. In parallel, we also identified
      colocalization of hypoxic regions and various lipid species such as
      PC(16:0/18:0), PC(16:0/18:1), PC(16:0/18:2), PC(16:1/18:4), PC(18:0/18:1), and
      PC(18:1/18:1), among others. Our findings shed light on the biomolecular
      composition of hypoxic tumor regions, which may be responsible for a given
      tumor's resistance to radiation or chemotherapy. 

PMID- 25993306
TI  - Barriers and enablers of kangaroo mother care practice: a systematic review.
AB  - Kangaroo mother care (KMC) is an evidence-based approach to reducing mortality
      and morbidity in preterm infants. Although KMC is a key intervention package in
      newborn health initiatives, there is limited systematic information available on
      the barriers to KMC practice that mothers and other stakeholders face while
      practicing KMC. This systematic review sought to identify the most frequently
      reported barriers to KMC practice for mothers, fathers, and health practitioners,
      as well as the most frequently reported enablers to practice for mothers. We
      searched nine electronic databases and relevant reference lists for publications
      reporting barriers or enablers to KMC practice. We identified 1,264 unique
      publications, of which 103 were included based on pre-specified criteria.
      Publications were scanned for all barriers / enablers. Each publication was also
      categorized based on its approach to identification of barriers / enablers, and
      more weight was assigned to publications which had systematically sought to
      understand factors influencing KMC practice. Four of the top five ranked barriers
      to KMC practice for mothers were resource-related: "Issues with the facility
      environment / resources," "negative impressions of staff attitudes or
      interactions with staff," "lack of help with KMC practice or other obligations,"
      and "low awareness of KMC / infant health." Considering only publications from
      low- and middle-income countries, "pain / fatigue" was ranked higher than when
      considering all publications. Top enablers to practice were included "mother
      infant attachment" and "support from family, friends, and other mentors." Our
      findings suggest that mother can understand and enjoy KMC, and it has benefits
      for mothers, infants, and families. However, continuous KMC may be physically and
      emotionally difficult, and often requires support from family members, health
      practitioners, or other mothers. These findings can serve as a starting point for
      researchers and program implementers looking to improve KMC programs. 

PMID- 25993307
TI  - Perceived Barriers for Accessing Health Services among Individuals with
      Disability in Four African Countries.
AB  - There is an increasing awareness among researchers and others that marginalized
      and vulnerable groups face problems in accessing health care. Access problems in
      particular in low-income countries may jeopardize the targets set by the United
      Nations through the Millennium Development Goals. Thus, identifying barriers for
      individuals with disability in accessing health services is a research priority.
      The current study aimed at identifying the magnitude of specific barriers, and to
      estimate the impact of disability on barriers for accessing health care in
      general. A population based household survey was carried out in Sudan, Namibia,
      Malawi, and South Africa, including a total of 9307 individuals. The sampling
      strategy was a two-stage cluster sampling within selected geographical areas in
      each country. A listing procedure to identify households with disabled members
      using the Washington Group six screening question was followed by administering
      household questionnaires in households with and without disabled members, and
      questionnaires for individuals with and without disability. The study shows that
      lack of transport, availability of services, inadequate drugs or equipment, and
      costs, are the four major barriers for access. The study also showed substantial
      variation in perceived barriers, reflecting largely socio-economic differences
      between the participating countries. Urbanity, socio-economic status, and
      severity of activity limitations are important predictors for barriers, while
      there is no gender difference. It is suggested that education reduces barriers to
      health services only to the extent that it reduces poverty. Persons with
      disability face additional and particular barriers to health services. Addressing
      these barriers requires an approach to health that stresses equity over equality.

PMID- 25993308
TI  - Impact of Open Data Policies on Consent to Participate in Human Subjects
      Research: Discrepancies between Participant Action and Reported Concerns.
AB  - Research outlets are increasingly adopting open data policies as a requisite for
      publication, including studies with human subjects data. We investigated whether
      open data policies influence participants' rate of consent by randomly assigning
      participants to view consent forms with and without discussion of open data
      policies. No participants declined to participate, regardless of condition, nor
      did rates of drop-out vs. completion vary between conditions. Furthermore, no
      significant change in potential consent rates was reported when participants were
      openly asked about the influence of open data policies on their likelihood of
      consent. However, follow-up analyses indicated possible poor attention to consent
      forms, consistent with previous research. Moreover, thematic analysis of
      participants' considerations of open data policy indicated multiple
      considerations such as concerns regarding confidentiality, anonymity, data
      security, and study sensitivity. The impact of open data policies on
      participation raises complex issues at the intersection of ethics and scientific
      innovation. We conclude by encouraging researchers to consider participants as
      stakeholders in open data policy and by providing recommendations for open data
      policies in human subjects research. 

PMID- 25993309
TI  - Efficient access to novel androsteno-17-(1',3',4')-oxadiazoles and 17beta
      (1',3',4')-thiadiazoles via N-substituted hydrazone and N,N'-disubstituted
      hydrazine intermediates, and their pharmacological evaluation in vitro.
AB  - A series of novel 17-exo-oxadiazoles and -thiadiazoles in the Delta(5) androstene
      series were efficiently synthesized from pregnenolone acetate and pregnadienolone
      acetate via multistep pathways. 17beta-(1',3',4')-Oxadiazoles were obtained in
      high yields by the phenyliodonium diacetate-induced oxidative ring closure of
      semicarbazone and N-acylhydrazones derived from 3beta-acetoxy- and 3beta
      hydroxyandrost-5-ene-17beta-carbaldehydes. For the synthesis of analogous
      Delta(16)-17-oxadiazolyl derivatives, N,N'-disubstituted hydrazine intermediates
      were prepared from 3beta-acetoxyandrosta-5,16-diene-17-carboxylic acid, which
      then underwent cyclodehydration in the presence of POCl3. The cyclization of
      steroidal N,N'-diacylhydrazines containing a saturated ring D with the Lawesson
      reagent afforded 17beta-(1',3',4')-thiadiazoles in good yields. Most of the
      products were subjected to deacetylation in basic media in order to enlarge the
      compound library available for pharmacological studies. All of these derivatives
      were screened in vitro for their antiproliferative effects against four malignant
      human adherent cell lines (HeLa, A2780, MCF7 and A431) by means of the MTT assay.
      The 3beta-hydroxy derivatives of the newly-synthesized 17-exo-heterocycles were
      tested in vitro to investigate their inhibitory effects on rat testicular C17,20
      lyase. One of the 1,3,4-oxadiazolyl derivatives proved to exert noteworthy enzyme
      inhibitory action, with an IC50 (0.065 MUM) of the same order of magnitude as
      that of abiraterone. 

PMID- 25993310
TI  - Distinctive Structure of the EphA3/Ephrin-A5 Complex Reveals a Dual Mode of Eph
      Receptor Interaction for Ephrin-A5.
AB  - The Eph receptor tyrosine kinase/ephrin ligand system regulates a wide spectrum
      of physiological processes, while its dysregulation has been implicated in cancer
      progression. The human EphA3 receptor is widely upregulated in the tumor
      microenvironment and is highly expressed in some types of cancer cells.
      Furthermore, EphA3 is among the most highly mutated genes in lung cancer and it
      is also frequently mutated in other cancers. We report the structure of the
      ligand-binding domain of the EphA3 receptor in complex with its preferred ligand,
      ephrin-A5. The structure of the complex reveals a pronounced tilt of the ephrin
      A5 ligand compared to its orientation when bound to the EphA2 and EphB2 receptors
      and similar to its orientation when bound to EphA4. This tilt brings an
      additional area of ephrin-A5 into contact with regions of EphA3 outside the
      ephrin-binding pocket thereby enlarging the size of the interface, which is
      consistent with the high binding affinity of ephrin-A5 for EphA3. This large
      variation in the tilt of ephrin-A5 bound to different Eph receptors has not been
      previously observed for other ephrins. 

PMID- 25993312
TI  - Large tonsillolith associated with the accessory duct of the ipsilateral
      submandibular gland: support for saliva stasis hypothesis.
AB  - Tonsillolith is a calcified mass in the tonsil and/or its surrounding tissue,
      which is considered to be caused by chronic tonsillitis. However, here we
      hypothesized that a tonsillolith can also be formed by chronic saliva stasis in
      the tonsillar tissue, without any signs of chronic inflammation. We present the
      case of a 32-year-old male patient with a large tonsillolith. We reviewed his
      medical files, pre-operative imaging and intraoperative findings. During a
      standard tonsillectomy, we encountered a large tonsillolith measuring 3.1 * 2.6
      cm. Additionally, a careful dissection of the lower pole of the remaining
      tonsillar tissue revealed a large fistulous tract filled with saliva. Post
      operative examination of the pre-operative CT scan found a hypodense fistulous
      tract extending from the lower tonsillar pole towards the left submandibular
      gland, measuring 36 mm in length, which was diagnosed as an accessory duct of the
      submandibular gland. To our knowledge, this is the first case of a large
      tonsillolith associated with the accessory duct of the ipsilateral major salivary
      gland. Furthermore, from the aetiopathological view, this finding supports the
      saliva stasis hypothesis for formation of the tonsillolith. However, larger
      studies, including a detailed radiological analysis as in our case, are needed to
      further investigate this possible aetiology of tonsilloliths. 

PMID- 25993313
TI  - Ambient Stable Trigonal Bipyramidal Copper(III) Complexes Equipped with an
      Exchangeable Axial Ligand.
AB  - A stable trigonal bipyramidal copper(III) complex, [PPN][Cu((TMS)PS3)Cl] (1,
      wherein PPN represents bis(triphenylphosphine)iminium), was synthesized from
      CuCl2/PPNCl via intramolecular copper(II) disproportionation. Under ambient
      conditions, the axial chloride of 1 is exchangeable in solution thus making 1
      serve as an intermediate to prepare trigonal bipyramidal copper(III) derivatives,
      e.g., [PPN][Cu((TMS)PS3)(N3)] (2) and [Cu((TMS)PS3)(DABCO)] (3). Diamagnetic
      complexes 1-3 were fully characterized by X-ray crystallography, NMR, UV-vis, and
      Cu K-edge absorption spectroscopy. A series of UV-vis titrations were performed
      to investigate the relative ligand affinity toward the [Cu((TMS)PS3)] moiety,
      verifying the 1:1 binding equilibrium between various ligands. Compared to known
      copper(III) compounds, Cu K-edge absorptions of 1-3 possess lower pre-edge energy
      and higher shakedown transition energy, which, respectively, attribute to the
      electron donation from (TMS)PS3(3-) ligand and their trigonal ligand field. 

PMID- 25993311
TI  - Casein Kinase 1 and Phosphorylation of Cohesin Subunit Rec11 (SA3) Promote
      Meiotic Recombination through Linear Element Formation.
AB  - Proper meiotic chromosome segregation, essential for sexual reproduction,
      requires timely formation and removal of sister chromatid cohesion and crossing
      over between homologs. Early in meiosis cohesins hold sisters together and also
      promote formation of DNA double-strand breaks, obligate precursors to crossovers.
      Later, cohesin cleavage allows chromosome segregation. We show that in fission
      yeast redundant casein kinase 1 homologs, Hhp1 and Hhp2, previously shown to
      regulate segregation via phosphorylation of the Rec8 cohesin subunit, are also
      required for high-level meiotic DNA breakage and recombination. Unexpectedly,
      these kinases also mediate phosphorylation of a different meiosis-specific
      cohesin subunit Rec11. This phosphorylation in turn leads to loading of linear
      element proteins Rec10 and Rec27, related to synaptonemal complex proteins of
      other species, and thereby promotes DNA breakage and recombination. Our results
      provide novel insights into the regulation of chromosomal features required for
      crossing-over and successful reproduction. The mammalian functional homolog of
      Rec11 (STAG3) is also phosphorylated during meiosis and appears to be required
      for fertility, indicating wide conservation of the meiotic events reported here. 

PMID- 25993314
TI  - Selectively manipulable acoustic-powered microswimmers.
AB  - Selective actuation of a single microswimmer from within a diverse group would be
      a first step toward collaborative guided action by a group of swimmers. Here we
      describe a new class of microswimmer that accomplishes this goal. Our swimmer
      design overcomes the commonly-held design paradigm that microswimmers must use
      non-reciprocal motion to achieve propulsion; instead, the swimmer is propelled by
      oscillatory motion of an air bubble trapped within the swimmer's polymer body.
      This oscillatory motion is driven by the application of a low-power acoustic
      field, which is biocompatible with biological samples and with the ambient
      liquid. This acoustically-powered microswimmer accomplishes controllable and
      rapid translational and rotational motion, even in highly viscous liquids (with
      viscosity 6,000 times higher than that of water). And by using a group of
      swimmers each with a unique bubble size (and resulting unique resonance
      frequencies), selective actuation of a single swimmer from among the group can be
      readily achieved. 

PMID- 25993315
TI  - Synergistic Potentials of Coffee on Injured Pancreatic Islets and Insulin Action
      via KATP Channel Blocking in Zebrafish.
AB  - Pancreatic islets (PIs) are damaged under diabetic conditions, resulting in
      decreased PI size. This study examined the regenerative effects of coffee and its
      components (caffeine, CFI; trigonelline, TRG; chlorogenic acid, CGA) on zebrafish
      larval PIs and beta-cells damaged by administration of alloxan (AX). In addition,
      the influence of coffee and its active components on KATP channels was
      investigated using diazoxide (DZ) as a KATP channel activator. PI size and
      fluorescence intensity were significantly increased in the coffee-treated group
      relative to the no-treatment group (P < 0.0001). In addition, coffee exerted
      significant regenerative effects on pancreatic beta-cells (p = 0.006). Treatment
      with TRG and CGA rescued PI damage, and the combination of TRG/CGA had a
      synergistic effect. In conclusion, the results indicate that coffee has
      beneficial effects on AX-damaged PIs and may also be useful as a blocker of
      pancreatic beta-cell K(+) channels. 

PMID- 25993316
TI  - Multiplex Real-Time PCR Assay Using TaqMan Probes for the Identification of
      Trypanosoma cruzi DTUs in Biological and Clinical Samples.
AB  - BACKGROUND: Trypanosoma cruzi has been classified into six Discrete Typing Units
      (DTUs), designated as TcI-TcVI. In order to effectively use this standardized
      nomenclature, a reproducible genotyping strategy is imperative. Several typing
      schemes have been developed with variable levels of complexity, selectivity and
      analytical sensitivity. Most of them can be only applied to cultured stocks. In
      this context, we aimed to develop a multiplex Real-Time PCR method to identify
      the six T. cruzi DTUs using TaqMan probes (MTq-PCR). METHODS/PRINCIPAL FINDINGS:
      The MTq-PCR has been evaluated in 39 cultured stocks and 307 biological samples
      from vectors, reservoirs and patients from different geographical regions and
      transmission cycles in comparison with a multi-locus conventional PCR algorithm.
      The MTq-PCR was inclusive for laboratory stocks and natural isolates and
      sensitive for direct typing of different biological samples from vectors,
      reservoirs and patients with acute, congenital infection or Chagas reactivation.
      The first round SL-IR MTq-PCR detected 1 fg DNA/reaction tube of TcI, TcII and
      TcIII and 1 pg DNA/reaction tube of TcIV, TcV and TcVI reference strains. The MTq
      PCR was able to characterize DTUs in 83% of triatomine and 96% of reservoir
      samples that had been typed by conventional PCR methods. Regarding clinical
      samples, 100% of those derived from acute infected patients, 62.5% from
      congenitally infected children and 50% from patients with clinical reactivation
      could be genotyped. Sensitivity for direct typing of blood samples from chronic
      Chagas disease patients (32.8% from asymptomatic and 22.2% from symptomatic
      patients) and mixed infections was lower than that of the conventional PCR
      algorithm. CONCLUSIONS/SIGNIFICANCE: Typing is resolved after a single or a
      second round of Real-Time PCR, depending on the DTU. This format reduces
      carryover contamination and is amenable to quantification, automation and kit
      production.

PMID- 25993317
TI  - Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating
      regulatory T cells by the CD206 mannose receptor.
AB  - Previously, we found that Foxp3-expressing CD4(+) regulatory T (Treg) cells
      attenuate cisplatin-induced acute kidney injury in mice and that bee venom and
      its constituent phospholipase A2 (PLA2) are capable of modulating Treg cells.
      Here we tested whether PLA2 could inhibit cisplatin-induced acute kidney injury.
      As a result of treatment with PLA2, the population of Treg cells was
      significantly increased, both in vivo and in vitro. PLA2-injected mice showed
      reduced levels of serum creatinine, blood urea nitrogen, renal tissue damage, and
      pro-inflammatory cytokine production upon cisplatin administration. These
      renoprotective effects were abolished by depletion of Treg cells. Furthermore,
      PLA2 bound to CD206 mannose receptors on dendritic cells, essential for the PLA2
      mediated protective effects on renal dysfunction. Interestingly, PLA2 treatment
      increased the secretion of IL-10 in the kidney from normal mice. Foxp3(+)IL-10(+)
      cells and CD11c(+)IL-10(+) cells were increased by PLA2 treatment. The anticancer
      effects of repeated administrations of a low dose of cisplatin were not affected
      by PLA2 treatment in a tumor-bearing model. Thus, PLA2 may prevent inflammatory
      responses in cisplatin-induced acute kidney injury by modulating Treg cells and
      IL-10 through the CD206 mannose receptor. 

PMID- 25993318
TI  - Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.
AB  - The Wilms' tumor suppressor WT1 is a key regulator of podocyte function that is
      mutated in Denys-Drash and Frasier syndromes. Here we have used an integrative
      approach employing ChIP, exon array, and genetic analyses in mice to address
      general and isoform-specific functions of WT1 in podocyte differentiation.
      Analysis of ChIP-Seq data showed that almost half of the podocyte-specific genes
      are direct targets of WT1. Bioinformatic analysis further identified coactivator
      FOXC1-binding sites in proximity to WT1-bound regions, thus supporting
      coordinated action of these transcription factors in regulating podocyte-specific
      genes. Transcriptional profiling of mice lacking the WT1 alternative splice
      isoform (+KTS) had a more restrictive set of genes whose expression depends on
      these alternatively spliced isoforms. One of these genes encodes the membrane
      associated guanylate kinase MAGI2, a protein that localizes to the base of the
      slit diaphragm. Using functional analysis in mice, we further show that
      MAGI2alpha is essential for proper localization of nephrin and the assembly of
      the slit diaphragm complex. Finally, a dramatic reduction of MAGI2 was found in
      an LPS mouse model of glomerular injury and in genetic cases of human disease.
      Thus, our study highlights the central role of WT1 in podocyte differentiation,
      identifies that WT1 has a central role in podocyte differentiation, and
      identifies MAGI2alpha as the crucial isoform in slit diaphragm assembly,
      suggesting a causative role of this gene in the etiology of glomerular disorders.

PMID- 25993319
TI  - Sequencing rare and common APOL1 coding variants to determine kidney disease
      risk.
AB  - A third of African Americans with sporadic focal segmental glomerulosclerosis
      (FSGS) or HIV-associated nephropathy (HIVAN) do not carry APOL1 renal risk
      genotypes. This raises the possibility that other APOL1 variants may contribute
      to kidney disease. To address this question, we sequenced all APOL1 exons in 1437
      Americans of African and European descent, including 464 patients with biopsy
      proven FSGS/HIVAN. Testing for association with 33 common and rare variants with
      FSGS/HIVAN revealed no association independent of strong recessive G1 and G2
      effects. Seeking additional variants that might have been under selection by
      pathogens and could represent candidates for kidney disease risk, we also
      sequenced an additional 1112 individuals representing 53 global populations.
      Except for G1 and G2, none of the 7 common codon-altering variants showed
      evidence of selection or could restore lysis against trypanosomes causing human
      African trypanosomiasis. Thus, only APOL1 G1 and G2 confer renal risk, and other
      common and rare APOL1 missense variants, including the archaic G3 haplotype, do
      not contribute to sporadic FSGS and HIVAN in the US population. Hence, in most
      potential clinical or screening applications, our study suggests that sequencing
      APOL1 exons is unlikely to bring additional information compared to genotyping
      only APOL1 G1 and G2 risk alleles.

PMID- 25993320
TI  - CD154-CD40 T-cell co-stimulation pathway is a key mechanism in kidney ischemia
      reperfusion injury.
AB  - Ischemia-reperfusion occurs in a great many clinical settings and contributes to
      organ failure or dysfunction. CD154-CD40 signaling in leukocyte-endothelial cell
      interactions or T-cell activation facilitates tissue inflammation and injury.
      Here we tested a siRNA anti-CD40 in rodent warm and cold ischemia models to check
      the therapeutic efficacy and anti-inflammatory outcome of in vivo gene silencing.
      In the warm ischemia model different doses were used, resulting in clear renal
      function improvement and a structural renoprotective effect. Renal ischemia
      activated the CD40 gene and protein expression, which was inhibited by
      intravenous siRNA administration. CD40 gene silencing improved renal inflammatory
      status, as seen by the reduction of CD68 and CD3 T-cell infiltrates, attenuated
      pro-inflammatory, and enhanced anti-inflammatory mediators. Furthermore, siRNA
      administration decreased a spleen pro-inflammatory monocyte subset and reduced
      TNFalpha secretion by splenic T cells. In the cold ischemia model with syngeneic
      and allogeneic renal transplantation, the most effective dose induced similar
      functional and structural renoprotective effects. Our data show the efficacy of
      our siRNA in modulating both the local and the systemic inflammatory milieu after
      an ischemic insult. Thus, CD40 silencing could emerge as a novel therapeutic
      strategy in solid organ transplantation. 

PMID- 25993321
TI  - Glomerular parietal epithelial cells contribute to adult podocyte regeneration in
      experimental focal segmental glomerulosclerosis.
AB  - As adult podocytes cannot adequately proliferate following depletion in disease
      states, there has been interest in the potential role of progenitors in podocyte
      repair and regeneration. To determine whether parietal epithelial cells (PECs)
      can serve as adult podocyte progenitors following disease-induced podocyte
      depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice.
      In normal mice, labeled PECs were confined to Bowman's capsule, whereas in
      disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the
      glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in
      disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when
      podocyte numbers were significantly higher and disease severity was significantly
      lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44.
      Neither labeled PECs on the tuft nor podocytes stained for the proliferation
      marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing
      PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of
      focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed
      by regeneration, PECs undergo two phenotypic changes once they migrate to the
      glomerular tuft. Initially these cells are predominantly activated CD44
      expressing cells coinciding with glomerulosclerosis, and later they predominantly
      exhibit a podocyte phenotype, which is likely reparative. 

PMID- 25993322
TI  - Renal systems biology of patients with systemic inflammatory response syndrome.
AB  - A systems biology approach was used to comprehensively examine the impact of
      renal disease and hemodialysis (HD) on patient response during critical illness.
      To achieve this, we examined the metabolome, proteome, and transcriptome of 150
      patients with critical illness, stratified by renal function. Quantification of
      plasma metabolites indicated greater change as renal function declined, with the
      greatest derangements in patients receiving chronic HD. Specifically, 6 uremic
      retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7
      pentose phosphate sugars increased as renal function declined, consistent with
      decreased excretion or increased catabolism of amino acids and ribonucleotides.
      Similarly, the proteome showed increased levels of low-molecular-weight proteins
      and acute-phase reactants. The transcriptome revealed a broad-based decrease in
      mRNA levels among patients on HD. Systems integration revealed an unrecognized
      association between plasma RNASE1 and several RNA catabolites and modified
      nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N
      acetylaspartate were inversely correlated with the majority of significantly
      downregulated genes. Thus, renal function broadly affected the plasma metabolome,
      proteome, and peripheral blood transcriptome during critical illness; changes
      were not effectively mitigated by hemodialysis. These studies allude to several
      novel mechanisms whereby renal dysfunction contributes to critical illness.

PMID- 25993324
TI  - Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea
      transporters UT-A and UT-B in rats.
AB  - Inhibitors of kidney urea transporter (UT) proteins have potential use as salt
      sparing diuretics ('urearetics') with a different mechanism of action than
      diuretics that target salt transporters. To study UT inhibition in rats, we
      screened about 10,000 drugs, natural products and urea analogs for inhibition of
      rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an
      indolcarbonylchromenone with IC50 of 10-20 MUM. Urea analog screening found
      methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited
      rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2-3 mM. Homology
      modeling and docking computations suggested DMTU binding sites on rat UT-A1.
      Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma
      concentration was 9 mM with t1/2 of about 10 h, and a urine concentration of 20
      40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction
      in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and
      mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a
      low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had
      greater diuresis and reduced urinary salt loss. In a model of syndrome of
      inappropriate antidiuretic hormone secretion, DMTU treatment prevented
      hyponatremia and water retention produced by water-loading in dDAVP-treated rats.
      Thus, our results establish a rat model of UT inhibition and demonstrate the
      diuretic efficacy of UT inhibition.

PMID- 25993325
TI  - A standardized method for the analysis of liver sinusoidal endothelial cells and
      their fenestrations by scanning electron microscopy.
AB  - Liver sinusoidal endothelial cells are the gateway to the liver, their
      transcellular fenestrations allow the unimpeded transfer of small and dissolved
      substances from the blood into the liver parenchyma for metabolism and
      processing. Fenestrations are dynamic structures--both their size and/or number
      can be altered in response to various physiological states, drugs, and disease,
      making them an important target for modulation. An understanding of how LSEC
      morphology is influenced by various disease, toxic, and physiological states and
      how these changes impact on liver function requires accurate measurement of the
      size and number of fenestrations. In this paper, we describe scanning electron
      microscopy fixation and processing techniques used in our laboratory to ensure
      reproducible specimen preparation and accurate interpretation. The methods
      include perfusion fixation, secondary fixation and dehydration, preparation for
      the scanning electron microscope and analysis. Finally, we provide a step by step
      method for standardized image analysis which will benefit all researchers in the
      field.

PMID- 25993323
TI  - Recent developments in epigenetics of acute and chronic kidney diseases.
AB  - The growing epidemic of obesity and diabetes, the aging population as well as
      prevalence of drug abuse has led to significant increases in the rates of the
      closely associated acute and chronic kidney diseases, including diabetic
      nephropathy. Furthermore, evidence shows that parental behavior and diet can
      affect the phenotype of subsequent generations via epigenetic transmission
      mechanisms. These data suggest a strong influence of the environment on disease
      susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms
      need to be evaluated to gain critical new information about kidney diseases.
      Epigenetics is the study of processes that control gene expression and phenotype
      without alterations in the underlying DNA sequence. Epigenetic modifications,
      including cytosine DNA methylation and covalent post-translational modifications
      of histones in chromatin, are part of the epigenome, the interface between the
      stable genome and the variable environment. This dynamic epigenetic layer
      responds to external environmental cues to influence the expression of genes
      associated with disease states. The field of epigenetics has seen remarkable
      growth in the past few years with significant advances in basic biology,
      contributions to human disease, as well as epigenomics technologies. Further
      understanding of how the renal cell epigenome is altered by metabolic and other
      stimuli can yield novel new insights into the pathogenesis of kidney diseases. In
      this review, we have discussed the current knowledge on the role of epigenetic
      mechanisms (primarily DNAme and histone modifications) in acute and chronic
      kidney diseases, and their translational potential to identify much needed new
      therapies. 

PMID- 25993326
TI  - Water organic pollution and eutrophication influence soil microbial processes,
      increasing soil respiration of estuarine wetlands: site study in jiuduansha
      wetland.
AB  - Undisturbed natural wetlands are important carbon sinks due to their low soil
      respiration. When compared with inland alpine wetlands, estuarine wetlands in
      densely populated areas are subjected to great pressure associated with
      environmental pollution. However, the effects of water pollution and
      eutrophication on soil respiration of estuarine and their mechanism have still
      not been thoroughly investigated. In this study, two representative zones of a
      tidal wetland located in the upstream and downstream were investigated to
      determine the effects of water organic pollution and eutrophication on soil
      respiration of estuarine wetlands and its mechanism. The results showed that
      eutrophication, which is a result of there being an excess of nutrients including
      nitrogen and phosphorus, and organic pollutants in the water near Shang shoal
      located upstream were higher than in downstream Xia shoal. Due to the absorption
      and interception function of shoals, there to be more nitrogen, phosphorus and
      organic matter in Shang shoal soil than in Xia shoal. Abundant nitrogen,
      phosphorus and organic carbon input to soil of Shang shoal promoted reproduction
      and growth of some highly heterotrophic metabolic microorganisms such as beta
      Proteobacteria, gamma-Proteobacteria and Acidobacteria which is not conducive to
      carbon sequestration. These results imply that the performance of pollutant
      interception and purification function of estuarine wetlands may weaken their
      carbon sequestration function to some extent. 

PMID- 25993327
TI  - Interaction Effects of Light, Temperature and Nutrient Limitations (N, P and Si)
      on Growth, Stoichiometry and Photosynthetic Parameters of the Cold-Water Diatom
      Chaetoceros wighamii.
AB  - Light (20-450 MUmol photons m(-2) s(-1)), temperature (3-11  degrees C) and
      inorganic nutrient composition (nutrient replete and N, P and Si limitation) were
      manipulated to study their combined influence on growth, stoichiometry (C:N:P:Chl
      a) and primary production of the cold water diatom Chaetoceros wighamii. During
      exponential growth, the maximum growth rate (~0.8 d(-1)) was observed at high
      temperature and light; at 3  degrees C the growth rate was ~30% lower under
      similar light conditions. The interaction effect of light and temperature were
      clearly visible from growth and cellular stoichiometry. The average C:N:P molar
      ratio was 80:13:1 during exponential growth, but the range, due to different
      light acclimation, was widest at the lowest temperature, reaching very low C:P
      (~50) and N:P ratios (~8) at low light and temperature. The C:Chl a ratio had
      also a wider range at the lowest temperature during exponential growth, ranging
      16-48 (weight ratio) at 3  degrees C compared with 17-33 at 11  degrees C. During
      exponential growth, there was no clear trend in the Chl a normalized, initial
      slope (alpha*) of the photosynthesis-irradiance (PE) curve, but the maximum
      photosynthetic production (P(m)) was highest for cultures acclimated to the
      highest light and temperature. During the stationary growth phase, the
      stoichiometric relationship depended on the limiting nutrient, but with generally
      increasing C:N:P ratio. The average photosynthetic quotient (PQ) during
      exponential growth was 1.26 but decreased to <1 under nutrient and light
      limitation, probably due to photorespiration. The results clearly demonstrate
      that there are interaction effects between light, temperature and nutrient
      limitation, and the data suggests greater variability of key parameters at low
      temperature. Understanding these dynamics will be important for improving models
      of aquatic primary production and biogeochemical cycles in a warming climate.

PMID- 25993328
TI  - Immunohistochemical Assessment of Phosphorylated mTORC1-Pathway Proteins in Human
      Brain Tumors.
AB  - BACKGROUND: Current pathological diagnostics include the analysis of (epi
      )genetic alterations as well as oncogenic pathways. Deregulated mammalian target
      of rapamycin complex 1 (mTORC1) signaling has been implicated in a variety of
      cancers including malignant gliomas and is considered a promising target in
      cancer treatment. Monitoring of mTORC1 activity before and during inhibitor
      therapy is essential. The aim of our study is to provide a recommendation and
      report on pitfalls in the use of phospho-specific antibodies against mTORC1
      targets phospho-RPS6 (Ser235/236; Ser240/244) and phospho-4EBP1 (Thr37/46) in
      formalin fixed, paraffin embedded material. METHODS AND FINDINGS: Primary,
      established cell lines and brain tumor tissue from routine diagnostics were
      assessed by immunocyto-, immunohistochemistry, immunofluorescent stainings and
      immunoblotting. For validation of results, immunoblotting experiments were
      performed. mTORC-pathway activation was pharmacologically inhibited by torin2 and
      rapamycin. Torin2 treatment led to a strong reduction of signal intensity and
      frequency of all tested antibodies. In contrast phospho-4EBP1 did not show
      considerable reduction in staining intensity after rapamycin treatment, while
      immunocytochemistry with both phospho-RPS6-specific antibodies showed a reduced
      signal compared to controls. Staining intensity of both phospho-RPS6-specific
      antibodies did not show considerable decrease in stability in a timeline from 0
      230 minutes without tissue fixation, however we observed a strong decrease of
      staining intensity in phospho-4EBP1 after 30 minutes. Detection of phospho
      signals was strongly dependent on tissue size and fixation gradient. mTORC1
      signaling was significantly induced in glioblastomas although not restricted to
      cancer cells but also detectable in non-neoplastic cells. CONCLUSION: Here we
      provide a recommendation for phospho-specific immunohistochemistry for patient
      orientated therapy decisions and monitoring treatment response.

PMID- 25993329
TI  - Spatial fingerprints of community structure in human interaction network for an
      extensive set of large-scale regions.
AB  - Human interaction networks inferred from country-wide telephone activity
      recordings were recently used to redraw political maps by projecting their
      topological partitions into geographical space. The results showed remarkable
      spatial cohesiveness of the network communities and a significant overlap between
      the redrawn and the administrative borders. Here we present a similar analysis
      based on one of the most popular online social networks represented by the ties
      between more than 5.8 million of its geo-located users. The worldwide coverage of
      their measured activity allowed us to analyze the large-scale regional subgraphs
      of entire continents and an extensive set of examples for single countries. We
      present results for North and South America, Europe and Asia. In our analysis we
      used the well-established method of modularity clustering after an aggregation of
      the individual links into a weighted graph connecting equal-area geographical
      pixels. Our results show fingerprints of both of the opposing forces of dividing
      local conflicts and of uniting cross-cultural trends of globalization. 

PMID- 25993331
TI  - Evaluating Changes in Health Care Policy: Methods Matter.

PMID- 25993333
TI  - Familial separations, coping styles, and PTSD symptomatology in resettled refugee
      youth.
AB  - Youth from refugee backgrounds have been found to experience high rates of
      posttraumatic stress disorder (PTSD), even after years of resettlement. The
      present study sought to investigate how familial separations and coping styles
      act as correlates of PTSD symptoms in resettled refugee youth (N = 50).
      Participants (Mage = 16.63; range: 12-21) completed self-report questionnaires
      assessing PTSD symptoms and their use of coping styles, and engaged in a semi
      structured interview designed by the authors to investigate their resettlement
      and adaptational experiences in Australia. Youth who were separated from
      immediate family members demonstrated significantly more PTSD symptoms than their
      counterparts, and there was a relationship between avoidant coping and PTSD,
      although this diminished once the confound between scales was controlled for.
      This study found evidence for the integrity of the family unit as a correlate of
      PTSD in refugee youth, but no evidence of a relationship between coping style and
      family separations.

PMID- 25993332
TI  - Selection of scFv Antibody Fragments Binding to Human Blood versus Lymphatic
      Endothelial Surface Antigens by Direct Cell Phage Display.
AB  - The identification of marker molecules specific for blood and lymphatic
      endothelium may provide new diagnostic tools and identify new targets for therapy
      of immune, microvascular and cancerous diseases. Here, we used a phage display
      library expressing human randomized single-chain Fv (scFv) antibodies for direct
      panning against live cultures of blood (BECs) and lymphatic (LECs) endothelial
      cells in solution. After six panning rounds, out of 944 sequenced antibody
      clones, we retrieved 166 unique/diverse scFv fragments, as indicated by the V
      region sequences. Specificities of these phage clone antibodies for respective
      compartments were individually tested by direct cell ELISA, indicating that
      mainly pan-endothelial cell (EC) binders had been selected, but also revealing a
      subset of BEC-specific scFv antibodies. The specific staining pattern was
      recapitulated by twelve phage-independently expressed scFv antibodies. Binding
      capacity to BECs and LECs and differential staining of BEC versus LEC by a subset
      of eight scFv antibodies was confirmed by immunofluorescence staining. As one
      antigen, CD146 was identified by immunoprecipitation with phage-independent scFv
      fragment. This antibody, B6-11, specifically bound to recombinant CD146, and to
      native CD146 expressed by BECs, melanoma cells and blood vessels. Further,
      binding capacity of B6-11 to CD146 was fully retained after fusion to a mouse Fc
      portion, which enabled eukaryotic cell expression. Beyond visualization and
      diagnosis, this antibody might be used as a functional tool. Overall, our
      approach provided a method to select antibodies specific for endothelial surface
      determinants in their native configuration. We successfully selected antibodies
      that bind to antigens expressed on the human endothelial cell surfaces in situ,
      showing that BECs and LECs share a majority of surface antigens, which is
      complemented by cell-type specific, unique markers. 

PMID- 25993334
TI  - Differences in the strength of cortical and brainstem inputs to SSA and non-SSA
      neurons in the inferior colliculus.
AB  - In an ever changing auditory scene, change detection is an ongoing task performed
      by the auditory brain. Neurons in the midbrain and auditory cortex that exhibit
      stimulus-specific adaptation (SSA) may contribute to this process. Those neurons
      adapt to frequent sounds while retaining their excitability to rare sounds. Here,
      we test whether neurons exhibiting SSA and those without are part of the same
      networks in the inferior colliculus (IC). We recorded the responses to frequent
      and rare sounds and then marked the sites of these neurons with a retrograde
      tracer to correlate the source of projections with the physiological response.
      SSA neurons were confined to the non-lemniscal subdivisions and exhibited broad
      receptive fields, while the non-SSA were confined to the central nucleus and
      displayed narrow receptive fields. SSA neurons receive strong inputs from
      auditory cortical areas and very poor or even absent projections from the
      brainstem nuclei. On the contrary, the major sources of inputs to the neurons
      that lacked SSA were from the brainstem nuclei. These findings demonstrate that
      auditory cortical inputs are biased in favor of IC synaptic domains that are
      populated by SSA neurons enabling them to compare top-down signals with incoming
      sensory information from lower areas. 

PMID- 25993335
TI  - Decreased memory B cells and increased CD8 memory T cells in blood of breastfed
      children: the generation R study.
AB  - BACKGROUND: Breastfeeding provides a protective effect against infectious
      diseases in infancy. Still, immunological evidence for enhanced adaptive immunity
      in breastfed children remains inconclusive. OBJECTIVE: To determine whether
      breastfeeding affects B- and T-cell memory in the first years of life. METHODS:
      We performed immunophenotypic analysis on blood samples within a population-based
      prospective cohort study. Participants included children at 6 months (n=258), 14
      months (n=166), 25 months (n=112) and 6 years of age (n=332) with both data on
      breastfeeding and blood lymphocytes. Total B- and T-cell numbers and their memory
      subsets were determined with 6-color flow cytometry. Mothers completed
      questionnaires on breastfeeding when their children were aged 2, 6, and 12
      months. Multiple linear regression models with adjustments for potential
      confounders were performed. RESULTS: Per month continuation of breastfeeding, a
      3% (95% CI -6, -1) decrease in CD27+IgM+, a 2% (95 CI % -5, -1) decrease in
      CD27+IgA+ and a 2% (95% CI -4, -1) decrease in CD27-IgG+ memory B cell numbers
      were observed at 6 months of age. CD8 T-cell numbers at 6 months of age were 20%
      (95% CI 3, 37) higher in breastfed than in non-breastfed infants. This was mainly
      found for central memory CD8 T cells and associated with exposure to breast milk,
      rather than duration. The same trend was observed at 14 months, but associations
      disappeared at older ages. CONCLUSIONS: Longer breastfeeding is associated with
      increased CD8 T-cell memory, but not B-cell memory numbers in the first 6 months
      of life. This transient skewing towards T cell memory might contribute to the
      protective effect against infectious diseases in infancy.

PMID- 25993336
TI  - Two Novel Motifs of Watermelon Silver Mottle Virus NSs Protein Are Responsible
      for RNA Silencing Suppression and Pathogenicity.
AB  - The NSs protein of Watermelon silver mottle virus (WSMoV) is the RNA silencing
      suppressor and pathogenicity determinant. In this study, serial deletion and
      point-mutation mutagenesis of conserved regions (CR) of NSs protein were
      performed, and the silencing suppression function was analyzed through
      agroinfiltration in Nicotiana benthamiana plants. We found two amino acid (aa)
      residues, H113 and Y398, are novel functional residues for RNA silencing
      suppression. Our further analyses demonstrated that H113 at the common epitope
      (CE) ((109)KFTMHNQ(117)), which is highly conserved in Asia type tospoviruses,
      and the benzene ring of Y398 at the C-terminal beta-sheet motif ((397)IYFL(400))
      affect NSs mRNA stability and protein stability, respectively, and are thus
      critical for NSs RNA silencing suppression. Additionally, protein expression of
      other six deleted (DeltaCR1-DeltaCR6) and five point-mutated (Y15A, Y27A, G180A,
      R181A and R212A) mutants were hampered and their silencing suppression ability
      was abolished. The accumulation of the mutant mRNAs and proteins, except Y398A,
      could be rescued or enhanced by co-infiltration with potyviral suppressor HC-Pro.
      When assayed with the attenuated Zucchini yellow mosaic virus vector in squash
      plants, the recombinants carrying individual seven point-mutated NSs proteins
      displayed symptoms much milder than the recombinant carrying the wild type NSs
      protein, suggesting that these aa residues also affect viral pathogenicity by
      suppressing the host silencing mechanism.

PMID- 25993338
TI  - Understanding fossil phytolith preservation: the role of partial dissolution in
      paleoecology and archaeology.
AB  - Opaline phytoliths are important microfossils used for paleoecological and
      archaeological reconstructions that are primarily based on relative ratios of
      specific morphotypes. Recent studies have shown that phytolith assemblages are
      prone to post-depositional alteration involving partial dissolution, however, the
      manner in which partial dissolution affects morphotype composition is poorly
      understood. Here we show that morphotype assemblages from four different plant
      species subjected to controlled partial dissolution are significantly different
      from the original assemblages, indicating that the stability of various
      morphotypes differs, mainly depending on their surface area to bulk ratios. This
      underlying mechanism produces distorted morphotype compositions in partially
      dissolved phytolith assemblages, bearing vast implications for morphotype-based
      paleoecological and archaeological interpretation. Together with analyses of
      phytolith assemblages from a variety of archaeological sites, our results
      establish criteria by which well-preserved phytolith assemblages can be selected
      for accurate paleoecological and archaeological reconstructions. 

PMID- 25993337
TI  - Ceramide as a mediator of non-alcoholic Fatty liver disease and associated
      atherosclerosis.
AB  - Cardiovascular disease (CVD) is a serious comorbidity in nonalcoholic fatty liver
      disease (NAFLD). Since plasma ceramides are increased in NAFLD and sphingomyelin,
      a ceramide metabolite, is an independent risk factor for CVD, the role of
      ceramides in dyslipidemia was assessed using LDLR(-/-) mice, a diet-induced model
      of NAFLD and atherosclerosis. Mice were fed a standard or Western diet (WD), with
      or without myriocin, an inhibitor of ceramide synthesis. Hepatic and plasma
      ceramides were profiled and lipid and lipoprotein kinetics were quantified.
      Hepatic and intestinal expression of genes and proteins involved in insulin,
      lipid and lipoprotein metabolism were also determined. WD caused hepatic
      oxidative stress, inflammation, apoptosis, increased hepatic long-chain ceramides
      associated with apoptosis (C16 and C18) and decreased very-long-chain ceramide
      C24 involved in insulin signaling. The plasma ratio of ApoB/ApoA1 (proteins of
      VLDL/LDL and HDL) was increased 2-fold due to increased ApoB production. Myriocin
      reduced hepatic and plasma ceramides and sphingomyelin, and decreased
      atherosclerosis, hepatic steatosis, fibrosis, and apoptosis without any effect on
      oxidative stress. These changes were associated with decreased lipogenesis, ApoB
      production and increased HDL turnover. Thus, modulation of ceramide synthesis may
      lead to the development of novel strategies for the treatment of both NAFLD and
      its associated atherosclerosis.

PMID- 25993341
TI  - Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus): Influential
      Factors and Reference Intervals.
AB  - Inshore common bottlenose dolphins (Tursiops truncatus) are exposed to a broad
      spectrum of natural and anthropogenic stressors. In response to these stressors,
      the mammalian adrenal gland releases hormones such as cortisol and aldosterone to
      maintain physiological and biochemical homeostasis. Consequently, adrenal gland
      dysfunction results in disruption of hormone secretion and an inappropriate
      stress response. Our objective herein was to develop diagnostic reference
      intervals (RIs) for adrenal hormones commonly associated with the stress response
      (i.e., cortisol, aldosterone) that account for the influence of intrinsic (e.g.,
      age, sex) and extrinsic (e.g., time) factors. Ultimately, these reference
      intervals will be used to gauge an individual's response to chase-capture stress
      and could indicate adrenal abnormalities. Linear mixed models (LMMs) were used to
      evaluate demographic and sampling factors contributing to differences in serum
      cortisol and aldosterone concentrations among bottlenose dolphins sampled in
      Sarasota Bay, Florida, USA (2000-2012). Serum cortisol concentrations were
      significantly associated with elapsed time from initial stimulation to sample
      collection (p<0.05), and RIs were constructed using nonparametric methods based
      on elapsed sampling time for dolphins sampled in less than 30 minutes following
      net deployment (95% RI: 0.91-4.21 ug/dL) and following biological sampling aboard
      a research vessel (95% RI: 2.32-6.68 ug/dL). To examine the applicability of the
      pre-sampling cortisol RI across multiple estuarine stocks, data from three
      additional southeast U.S. sites were compared, revealing that all of the dolphins
      sampled from the other sites (N = 34) had cortisol concentrations within the 95th
      percentile RI. Significant associations between serum concentrations of
      aldosterone and variables reported in previous studies (i.e., age, elapsed
      sampling time) were not observed in the current project (p<0.05). Also,
      approximately 16% of Sarasota Bay bottlenose dolphin aldosterone concentrations
      were below the assay's detection limit (11 pg/mL), thus hindering the ability to
      derive 95th percentile RIs. Serum aldosterone concentrations from animals sampled
      at the three additional sites were compared to the detection limit, and the
      proportion of animals with low aldosterone concentrations was not significantly
      different than an expected prevalence of 16%. Although this study relied upon
      long-term, free-ranging bottlenose dolphin health data from a single site, the
      objective RIs can be used for future evaluation of adrenal function among
      individuals sampled during capture-release health assessments. 

PMID- 25993340
TI  - FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium
      falciparum Exposure.
AB  - Exposure to Plasmodium falciparum is associated with circulating "atypical"
      memory B cells (atMBCs), which appear similar to dysfunctional B cells found in
      HIV-infected individuals. Functional analysis of atMBCs has been limited, with
      one report suggesting these cells are not dysfunctional but produce protective
      antibodies. To better understand the function of malaria-associated atMBCs, we
      performed global transcriptome analysis of these cells, obtained from individuals
      living in an area of high malaria endemicity in Uganda. Comparison of gene
      expression data suggested down-modulation of B cell receptor signaling and
      apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to
      previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not
      FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex
      vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs
      compromised in its ability to produce antibody upon stimulation. Moreover, higher
      levels of P. falciparum exposure were associated with increased frequencies of
      FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a
      functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals
      exposed to P. falciparum. 

PMID- 25993343
TI  - Oxygen Tolerance of a Molecular Engineered Cathode for Hydrogen Evolution Based
      on a Cobalt Diimine-Dioxime Catalyst.
AB  - We report here that a bioinspired cobalt diimine-dioxime molecular catalyst for
      hydrogen evolution immobilized onto carbon nanotube electrodes proves tolerant
      toward oxygen. The cobalt complex catalyzes O2 reduction with an onset potential
      of +0.55 V vs RHE. In this process, a mixture of water and hydrogen peroxide is
      produced in a 3:1 ratio. Our study evidences that such side-reductions have
      little impact on effectiveness of proton reduction by the grafted molecular
      catalyst which still displays good activity for H2 evolution in the presence of
      O2. The presence of O2 in the media is not detrimental toward H2 evolution under
      the conditions used, which simulate turn-on conditions of a water-splitting
      device. 

PMID- 25993342
TI  - Planting sentinel European trees in eastern Asia as a novel method to identify
      potential insect pest invaders.
AB  - Quarantine measures to prevent insect invasions tend to focus on well-known pests
      but a large proportion of the recent invaders were not known to cause significant
      damage in their native range, or were not even known to science before their
      introduction. A novel method is proposed to detect new potential pests of woody
      plants in their region of origin before they are introduced to a new continent.
      Since Asia is currently considered to be the main supplier of insect invaders to
      Europe, sentinel trees were planted in China during 2007-2011 as an early warning
      tool to identify the potential for additional Asian insect species to colonize
      European trees. Seedlings (1-1.5 m tall) of five broadleaved (Quercus petraea, Q.
      suber, Q. ilex, Fagus sylvatica, and Carpinus betulus) and two conifer species
      (Abies alba and Cupressus sempervirens) were planted in blocks of 100 seedlings
      at two widely separated sites (one in a nursery near Beijing and the other in a
      forest environment near Fuyang in eastern China), and then regularly surveyed for
      colonization by insects. A total of 104 insect species, mostly defoliators, were
      observed on these new hosts, and at least six species were capable of larval
      development. Although a number of the insects observed were probably incidental
      feeders, 38 species had more than five colonization events, mostly infesting Q.
      petraea, and could be considered as being capable of switching to European trees
      if introduced to Europe. Three years was shown to be an appropriate duration for
      the experiment, since the rate of colonization then tended to plateau. A majority
      of the identified species appeared to have switched from agricultural crops and
      fruit trees rather than from forest trees. Although these results are promising,
      the method is not appropriate for xylophagous pests and other groups developing
      on larger trees. Apart from the logistical problems, the identification to
      species level of the specimens collected was a major difficulty. This situation
      could be improved by the development of molecular databases. 

PMID- 25993344
TI  - Alcohol-related risk of suicidal ideation, suicide attempt, and completed
      suicide: a meta-analysis.
AB  - BACKGROUND: Several original studies have investigated the effect of alcohol use
      disorder (AUD) on suicidal thought and behavior, but there are serious
      discrepancies across the studies. Thus, a systematic assessment of the
      association between AUD and suicide is required. METHODS: We searched PubMed, Web
      of Science, and Scopus until February 2015. We also searched the Psycinfo web
      site and journals and contacted authors. We included observational (cohort, case
      control, and cross-sectional) studies addressing the association between AUD and
      suicide. The exposure of interest was AUD. The primary outcomes were suicidal
      ideation, suicide attempt, and completed suicide. We assessed heterogeneity using
      Q-test and I2 statistic. We explored publication bias using the Egger's and
      Begg's tests and funnel plot. We meta-analyzed the data with the random-effects
      models. For each outcome we calculated the overall odds ratio (OR) or risk ratio
      (RR) with 95% confidence intervals (CI). RESULTS: We included 31 out of 8548
      retrieved studies, with 420,732 participants. There was a significant association
      between AUD and suicidal ideation (OR=1.86; 95% CI: 1.38, 2.35), suicide attempt
      (OR=3.13; 95% CI: 2.45, 3.81); and completed suicide (OR=2.59; 95% CI: 1.95, 3.23
      and RR=1.74; 95% CI: 1.26, 2.21). There was a significant heterogeneity among the
      studies, but little concern to the presence of publication bias. CONCLUSIONS:
      There is sufficient evidence that AUD significantly increases the risk of
      suicidal ideation, suicide attempt, and completed suicide. Therefore, AUD can be
      considered an important predictor of suicide and a great source of premature
      death.

PMID- 25993345
TI  - Chelating sigma-Aryl Post-Metallocenes: Probing Intramolecular [C-H...F-C]
      Interactions and Unusual Reaction Pathways.
AB  - Our interest in chelating sigma-aryl ancillary ligands was motivated by their
      potential to impart unusual reactivity, since we envisioned that sigma-donors
      with minimal pi-donation would create a catalytic center with enhanced
      electrophilicity. We developed a family of Group 4 post-metallocene catalysts
      supported by pyridine-2-phenolate-6-(sigma-aryl) [O,N,C] ligands bearing a
      fluorinated moiety in the vicinity of the metal. Notable features of these meta
      substituted tris(hetero)aryl frameworks include their coordination geometry and
      inherent rigidity. For the first time, the elusive C-H...F-C interaction was
      manifested as NMR-discernible (1)H-(19)F coupling in solution and characterized
      by a neutron diffraction study. Their existence carries implications for catalyst
      design and in the context of weak attractive ligand-polymer interactions (WALPI),
      since they substantiate the practical viability of the ortho-F...H(beta) ligand
      polymer interactions proposed for living Group 4 fluorinated bis(phenoxyimine)
      catalysts. In metal-catalyzed olefin polymerization reactions, the notion of
      noncovalent interactions between an active ancillary ligand and the growing
      polymer chain is new. These interactions must be fragile and transient in nature,
      otherwise the intrinsic chain propagation process would be disrupted, and
      inherently tunable attractive forces such as hydrogen bonds are ideally suited to
      this role. The nature, relevance, and usability of extremely weak hydrogen bonds
      such as C-H...F-C has been a topical yet controversial area of research. We
      subsequently prepared a series of Group 4 complexes supported by fluorinated
      (sigma-aryl)-2-phenolate-6-pyridyl [O,C,N] ligands. [(1)H,(19)F]-HMBC NMR
      experiments were conducted to probe the observed (1)H-(19)F coupling, and
      specifically separate contributions from scalar (J) coupling and cross
      correlation (CR) interference. For the first time, a significant scalar component
      was confirmed for the (1)H-(19)F coupling in Ti-[O,C,N] and [O,N,C] complexes,
      which occurs with chemical connectivity across intramolecular C-H...F-C
      interactions. This result is important because the applicability of weak
      attractive ligand-polymer interactions in catalysis is feasible only if the
      observed coupling and hence the noncovalent interaction is genuine. The verified
      intramolecular C-H...F-C contacts in these complexes can therefore be considered
      as synthetic models for ligand-polymer interactions in olefin polymerization
      processes. Significantly, reports concerning late transition metal systems have
      appeared that hint at the generality of the WALPI concept for modulating
      polymerization reactions. We evaluated the olefin polymerization reactivity of Ti
      [O,N,C] catalysts through judicious substitution. DFT calculations, which
      revealed diverse kinetically competitive reaction pathways and active sites
      (including unusual ethylene-assimilated species) in addition to normal chain
      propagation, were also employed to rationalize polymerization efficiencies.
      Further developments in catalytic applications of multidentate sigma-aryl ligand
      systems and novel reactivity of the corresponding complexes can be envisaged. 

PMID- 25993346
TI  - Phylogeny, evolution and classification of gall wasps: the plot thickens.
AB  - Gall wasps (Cynipidae) represent the most spectacular radiation of gall-inducing
      insects. In addition to true gall formers, gall wasps also include phytophagous
      inquilines, which live inside the galls induced by gall wasps or other insects.
      Here we present the first comprehensive molecular and total-evidence analyses of
      higher-level gall wasp relationships. We studied more than 100 taxa representing
      a rich selection of outgroups and the majority of described cynipid genera
      outside the diverse oak gall wasps (Cynipini), which were more sparsely sampled.
      About 5 kb of nucleotide data from one mitochondrial (COI) and four nuclear (28S,
      LWRh, EF1alpha F1, and EF1alpha F2) markers were analyzed separately and in
      combination with morphological and life-history data. According to previous
      morphology-based studies, gall wasps evolved in the Northern Hemisphere and were
      initially herb gallers. Inquilines originated once from gall inducers that lost
      the ability to initiate galls. Our results, albeit not conclusive, suggest a
      different scenario. The first gall wasps were more likely associated with woody
      host plants, and there must have been multiple origins of gall inducers,
      inquilines or both. One possibility is that gall inducers arose independently
      from inquilines in several lineages. Except for these surprising results, our
      analyses are largely consistent with previous studies. They confirm that gall
      wasps are conservative in their host-plant preferences, and that herb-galling
      lineages have radiated repeatedly onto the same set of unrelated host plants. We
      propose a revised classification of the family into twelve tribes, which are
      strongly supported as monophyletic across independent datasets. Four are new:
      Aulacideini, Phanacidini, Diastrophini and Ceroptresini. We present a key to the
      tribes and discuss their morphological and biological diversity. Until the
      relationships among the tribes are resolved, the origin and early evolution of
      gall wasps will remain elusive. 

PMID- 25993348
TI  - Shallow methylmercury production in the marginal sea ice zone of the central
      Arctic Ocean.
AB  - Methylmercury (MeHg) is a neurotoxic compound that threatens wildlife and human
      health across the Arctic region. Though much is known about the source and
      dynamics of its inorganic mercury (Hg) precursor, the exact origin of the high
      MeHg concentrations in Arctic biota remains uncertain. Arctic coastal sediments,
      coastal marine waters and surface snow are known sites for MeHg production.
      Observations on marine Hg dynamics, however, have been restricted to the Canadian
      Archipelago and the Beaufort Sea (<79  degrees N). Here we present the first
      central Arctic Ocean (79-90  degrees N) profiles for total mercury (tHg) and
      MeHg. We find elevated tHg and MeHg concentrations in the marginal sea ice zone
      (81-85  degrees N). Similar to other open ocean basins, Arctic MeHg concentration
      maxima also occur in the pycnocline waters, but at much shallower depths (150-200
      m). The shallow MeHg maxima just below the productive surface layer possibly
      result in enhanced biological uptake at the base of the Arctic marine food web
      and may explain the elevated MeHg concentrations in Arctic biota. We suggest that
      Arctic warming, through thinning sea ice, extension of the seasonal sea ice zone,
      intensified surface ocean stratification and shifts in plankton ecodynamics, will
      likely lead to higher marine MeHg production.

PMID- 25993349
TI  - [Short- and Medium-Term Results of Total Elbow Arthroplasty after Trauma].
AB  - BACKGROUND: Treatment of distal humerus fractures by open reduction and internal
      fixation, especially in elderly patients, does not always result in satisfactory
      outcomes. Previous studies show good outcomes in total joint replacement of these
      fractures. The objective of this study is to present our experience with primary
      and secondary implantation of a semiconstrained elbow prosthesis after trauma.
      PATIENTS AND METHODS: In two study centers, between 2003 and 2009, a total of 44
      patients (34 women and 10 men) with an average age of 65 years were treated
      primarily (n = 19) or secondarily (n = 25) by semiconstrained total elbow
      replacement after distal humerus fractures. Primary treatment referred
      exclusively to 13C2 and 13C3 fractures according to the AO/ASIF-classification,
      except for two cases. Indications for secondary elbow arthroplasty were post
      traumatic arthrosis (n = 10), non-union of the bone (n = 6), failed
      osteosynthesis (n = 5), post-traumatic chronic luxation (n = 2) and severe bony
      defect situation after chronic osteitis (n = 2). In two cases a prostheses
      exchange for a periprosthetic fracture after fall was performed. Clinical outcome
      was radiologically controlled and measured by the use of the Mayo Elbow
      Performance Score (MEPS) and DASH score after a mean follow-up of 38 (13 to 96)
      months. RESULTS: 33 Patients (75 %) had a follow-up examination clinically and
      radiologically. Mayo Elbow Performance Score was excellent or good in 27 (82 %)
      cases with a mean of 87 points (primary group 87 vs. secondary group 86). The
      average DASH score was 28 points (primary group 24 vs. secondary group 32). The
      flexion was on average 131 degrees  (110 to 145 degrees ), the extension deficit
      30 degrees  (0 to 80 degrees ) to neutral position and the range of motion was
      100 degrees  (40 to 145 degrees ) (primary group 102 degrees  vs. secondary group
      97 degrees ). The mean operation time was 141 (100 to 250) minutes (primary group
      138 vs. secondary group 144 min.). The length of stay in hospital was on average
      15 days. Complications occurred due to ulnar paresthesia (n = 4), deep infection
      (n = 6), periprosthetic ulna fracture (n = 1), heterotopic ossifications
      requiring intervention (n = 1), elbow stiffness (n = 1), triceps insufficiency (n
      = 5) and triceps avulsion (n = 2). CONCLUSION: Primary elbow joint replacement
      seems to be a promising alternative for distal humerus fractures without a
      sufficient reconstruction opportunity, showing encouraging short- and medium-term
      results in the elderly. Secondary replacement can achieve satisfying results in
      failed osteosynthesis, non-union of the bone or post-traumatic arthrosis as well.
      The rate of complications and revisions is high.

PMID- 25993347
TI  - Functions that Protect Escherichia coli from Tightly Bound DNA-Protein Complexes
      Created by Mutant EcoRII Methyltransferase.
AB  - Expression of mutant EcoRII methyltransferase protein (M.EcoRII-C186A) in
      Escherichia coli leads to tightly bound DNA-protein complexes (TBCs), located
      sporadically on the chromosome rather than in tandem arrays. The mechanisms
      behind the lethality induced by such sporadic TBCs are not well studied, nor is
      it clear whether very tight binding but non-covalent complexes are processed in
      the same way as covalent DNA-protein crosslinks (DPCs). Using 2D gel
      electrophoresis, we found that TBCs induced by M.EcoRII-C186A block replication
      forks in vivo. Specific bubble molecules were detected as spots on the 2D gel,
      only when M.EcoRII-C186A was induced, and a mutation that eliminates a specific
      EcoRII methylation site led to disappearance of the corresponding spot. We also
      performed a candidate gene screen for mutants that are hypersensitive to TBCs
      induced by M.EcoRII-C186A. We found several gene products necessary for
      protection against these TBCs that are known to also protect against DPCs induced
      with wild-type M.EcoRII (after 5-azacytidine incorporation): RecA, RecBC, RecG,
      RuvABC, UvrD, FtsK, XerCD and SsrA (tmRNA). In contrast, the RecFOR pathway and
      Rep helicase are needed for protection against TBCs but not DPCs induced by
      M.EcoRII. We propose that stalled fork processing by RecFOR and RecA promotes
      release of tightly bound (but non-covalent) blocking proteins, perhaps by
      licensing Rep helicase-driven dissociation of the blocking M.EcoRII-C186A. Our
      studies also argued against the involvement of several proteins that might be
      expected to protect against TBCs. We took the opportunity to directly compare the
      sensitivity of all tested mutants to two quinolone antibiotics, which target
      bacterial type II topoisomerases and induce a unique form of DPC. We uncovered
      rep, ftsK and xerCD as novel quinolone hypersensitive mutants, and also obtained
      evidence against the involvement of a number of functions that might be expected
      to protect against quinolones. 

PMID- 25993350
TI  - [10-Year Follow-Up of the NexGen CR Total Knee Prosthesis].
AB  - BACKGROUND: The purpose of this study was to evaluate long-term clinical and
      radiological results as well as survival rates of the NexGen(r) CR posterior
      cruciate retaining prosthesis. PATIENTS AND METHODS: We evaluated a consecutive
      series of 761 total knee replacements performed on 716 patients from 1999 to 2001
      at our institution. All patients had been recorded prospectively in our in-house
      arthroplasty register. Follow-up data were available for 379 patients at 10 years
      postoperatively. Functional outcome was evaluated using the Knee Society score.
      An additional radiographic evaluation was performed on 224 patients at 10 years.
      The mean age of the patients at the time of surgery was 71 years. 75 % of the
      patients were female, 25 % were male. Mean BMI of the patients was 29.2 kg/m(2).
      The preoperative diagnosis was osteoarthritis in 91 %, rheumatoid arthritis in
      5,5 % and posttraumatic osteoarthritis in 2 %. Patella resurfacing was performed
      in 4 %. All components were cemented. RESULTS AND DISCUSSION: Mean Knee Society
      clinical score improved from 26.7 points preoperatively to 88.5 points at the
      time of the latest follow-up, and mean Knee Society function score improved from
      48.3 to 55.2 points. Flexion improved from a mean of 106.7 degrees 
      preoperatively to 111.4 degrees  at 10 years. Patellofemoral pain was indicated
      by 66 % of the patients before surgery and 4 % at the latest follow-up. 96 % were
      satisfied with the result of the surgery at 10 years. Radiographic evaluation was
      performed on 224 patients at the time of the latest follow-up. 203 patients (91
      %) had normal radiographic findings, 21 patients (9 %) showed pathological
      findings. Radiolucencies were seen in 18 patients on the AP view of the tibia, 1
      patient had an additional femoral radiolucency. There was an osteolysis located
      in the lateral tibia seen in 1 patient and an occurrence of heterotopic
      ossification in another patient. One knee showed a patella subluxation. No
      patient had radiographic evidence of loosening. 17 knees had required revision
      surgery with exchange of at least one of the components up to 10 years after the
      index procedure. 5 of the patients had revision for a deep infection, 2 for
      periprosthetic fractures of the distal femur with loosening of the prosthesis, 1
      for fracture of the proximal tibia due to osteoporosis, 4 for aseptic loosening,
      3 for instability and 2 for severe pain. Kaplan-Meier survival of all components
      using revision for any reason as the end point was 97.8 % at 10 years.
      CONCLUSION: The good clinical and radiological long-term results as well as the
      satisfactory survival rate after total knee replacement with the NexGen CR(r)
      prosthesis are comparable with the results of other long-term studies using the
      NexGen CR(r) and assimilable prosthesis. Our results demonstrate that quality of
      life was improved by the implantation of the NexGen CR(r) prosthesis even a long
      time after the index procedure despite old age and comorbidity of the patients.

PMID- 25993351
TI  - [Low-Carbon Metal-on-Metal Articulations for Hip Arthroplasties--Evaluation of
      Wear and Histology after 11 to 17 Years].
AB  - BACKGROUND: High-carbon (HC) alloys for hip arthroplasties were preferred to low
      carbon (LC) alloys for a long time because of their structurally hard carbide
      content. We opted for an LC alloy in 1994, because we expected it to be subject
      to less wear on account of its more homogeneous structure. Prompted by early
      complications not seen with ceramic-on-polyethylene mating surfaces, LC metal-on
      metal articulations were, however, given up by us in early 1999. A series of
      implants retrieved after 11 to 17 years was now studied to establish the actual
      amount of wear. Potential tissue reactions associated with hypersensitivity were
      also evaluated histologically and correlated with the measured wear and the
      amount of metal particles in capsular tissue. PATIENTS AND METHODS: Ten patients
      with LC metal-on-metal hip implants were the subjects of analyses after a mean
      follow-up time of 13.9 years. They underwent revision surgery because of
      osteolysis, cup loosening without dislocation, late infection in 1 patient and
      pain. The implant positions at the time of retrieval were the same as on the
      postoperative radiographs. Wear was determined in keeping with ISO 14242-2 and by
      SEM. In addition, periprosthetic tissue including the joint capsule and interface
      membranes were obtained for histological analysis. The amount of metal particles
      and the extent of lymphocyte infiltration were determined with the method
      described by Willert et al. Tissue alterations were evaluated histologically for
      signs of ALVAL using the method of Campbell et al. and correlated with the amount
      of wear and metal particles. RESULTS: The mean maximum linear wear rate was found
      to be 1.6 (1.0-2.1) um/year. Our data also showed a mean rate of 0.32 mm3/year
      (range, 0.22-0.47 mm3/year). This is equivalent to an annual metal release of 2.7
      (1.9-3.9) mg/year. No corrosion or corrosion products were present on the ball
      heads and their taper. All mating surfaces studied by SEM showed signs of
      abrasion. Sporadically, additional abrasions in the submicrometer range were
      detected on the ball head surfaces. These were caused by corundum particles
      detached from the blasted implant surfaces and interpreted as third-body wear
      below the level of quantification. Signs of impingement were absent.
      Histologically, metal wear particles of variable amount were detected in all
      cases. In 4 of them solid corrosion products were present in the tissue. The
      ALVAL scores were 5 to 10 (moderate to high), but did not correlate with the
      measured wear and the amount of metal particles. CONCLUSION: The wear of LC
      articulations found after years of implant survival was very low. In fact, it was
      lower than the data reported for HC articulations and would permit implants to
      function for decades in engineering terms. However, their survival is limited by
      tissue alterations associated with hypersensitivity. These tissue alterations may
      contribute to implant loosening as also reported for HC articulations. They are
      apparently not related to the actual amount of wear and may reflect adaptive
      immunological processes.

PMID- 25993353
TI  - Association of IL-6 and CRP gene polymorphisms with obesity and metabolic
      disorders in children and adolescents.
AB  - Activation of adipose tissue inflammation is associated with obesity caused by
      lipid accumulation in adipocytes. Through this activation, proinflammatory
      cytokines, such as Interleukin-6 (IL-6) and C-reactive protein (CRP) seem to
      influence metabolic disorders. The present study evaluated whether polymorphisms
      in the CRP (rs1205) and IL-6 (rs1800795, rs2069845) genes are associated with the
      development of metabolic disorders in children and adolescents. A cross-sectional
      study was performed, consisting of 470 students from the municipality of Santa
      Cruz do Sul, Brazil, aged 7-17 years. Body mass index (BMI) was classified
      according to overweight and obesity. Genotyping was performed by real-time
      Polymerase Chain Reaction (PCR). Anthropometric characteristics, biochemical
      markers, immunological markers and blood pressure were assessed. Descriptive
      statistics, chi-square and logistic regression were used for the analyses. No
      association was detected between the rs1800795 polymorphism and the assessed
      variables. Individuals with the risk genotype in the rs1205 gene were associated
      with the risk of developing hypercholesterolemia (OR 2.79; CI 1.40, 5.57; p =
      0.003). Carriers of the risk genotype in the rs2069845 gene are associated with
      the risk of developing obesity (OR 3.07; CI 1.08, 8.72; p = 0.03). The
      polymorphism rs2069845 was associated with obesity and rs1205 was associated with
      the risk of developing hypercholesterolemia in Brazilian schoolchildren. 

PMID- 25993352
TI  - [Orthopaedic Treatment for Patients with Myelomeningocele].
AB  - BACKGROUND: Due to prenatal diagnostic and folic acid prophylaxis less children
      with myelomeningocele are now being born. But they become older and need
      increasingly more orthopaedic care. The orthopaedic care is aimed at the
      improvement or the preservation of function. METHOD: In this review the current
      knowledge from the literature and our approach are presented. This is done in the
      context of the functional aspects within certain periods of life. Treatment
      Concept: In the first two years of life, the mobility of MMC children is
      supported by physiotherapy and orthoses irrespective of the level of the lesion.
      Afterwards, the optimal orthoses are chosen depending on the muscle power,
      emerging bone deformities, associated CNS malformation, shunt revisions, obesity
      and limitations in perception as well as the child's motivation. At school age,
      it is paramount to encourage independence. Orthotic treatment should be continued
      as long as the children benefit from it. Orthopaedic operations serve the
      orthosis fitting and the avoidance of pressure sores. Pathological fractures are
      common. They should be rapidly recognised in order to avoid further bony
      deformities. CONCLUSION: The aim of any orthopaedic treatment consists of the
      avoidance of musculoskeletal deformities in order to support the patient's self
      employment.

PMID- 25993354
TI  - Cytotoxic sesquiterpene lactones from the aerial parts of Inula aucheriana.
AB  - Inula aucheriana DC is a member of the family Asteraceae which is known to
      produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the
      present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide
      (stevin) and 14-acetoxy-1beta,5alpha,7alphaH-4beta-hydroxy-guai-9(10),11(13)-dien
      12,8alpha-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy
      1beta,5alpha,7alphaH-4beta-hydroxy-guai-9(10),11(13)-dien-12,8alpha-olide were
      further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide) assay to demonstrate cytotoxic activity with IC50 values of
      (56.6, 19.0), (39.0, 11.8), and (55.7, 15.3) MUg/mL against HepG-2, MCF-7 and A
      549 cells, respectively. The cytotoxic activity of the two evaluated
      sesquiterpene lactones partly explains the cytotoxic activity that was previously
      observed for the extracts of Inula aucheriana. The isolated compounds could be
      further investigated in cancer research studies. 

PMID- 25993355
TI  - Brazilian impact factor of physics journals--the third side of the coin.
AB  - The lack of correlation between the Journal Impact Factors and the most cited
      Brazilian papers in physics is statistically demonstrated. The existence of an
      effective "Brazilian Impact Factor" is observed, being its values, in general,
      lower than the international Impact Factors. In some cases, discrepancies from
      the international values are huge, leading to doubts on whether it is appropriate
      to use this indicator to judge Brazilian scientists. 

PMID- 25993356
TI  - Performance assessment of the database downscaled ocean waves (DOW) on Santa
      Catarina coast, South Brazil.
AB  - This work presents a validation of wave parameters from the new sixty years
      Downscaled Ocean Waves (DOW) reanalysis database. This study compares quantiles
      of the Gumbel distribution of Hs (significant wave height) and Tp (peak period)
      from simulated data with an 11 months' time series obtained from a buoy moored
      seaward on the Santa Catarina coast. Analysis by means of Gumbel distribution
      quantiles allows more weight to be given to the highest values of the time
      series, which are especially important in design projects. The statistical
      parameters used to verify the fit between the measured and the modeled data
      included: RMSE, BIAS, Scatter Index and Pearson Correlation Coefficient. Mean
      direction (thetam) validation was conducted qualitatively. The database showed
      good fit of the mean conditions, especially Hs which was well reproduced by the
      wave model. Underestimation of Tp, related mainly to the low spatial and temporal
      resolution of wind data used to generate waves, highlights this general modeling
      problem. Based on calculated statistical parameters, DOW data were considered
      comparable to the values obtained by measurements; however, such data must be
      cautiously used for extreme events analysis and in areas of bimodal sea
      conditions, where major deficiencies in the database were observed. 

PMID- 25993357
TI  - Adsorption of SOx and NOx in activated viscose fibers.
AB  - SOx and NOx are emissions resulting from combustion processes and are the main
      agents that contribute to the formation of acid rain, which causes harm to humans
      and the environment. Several techniques for removing these pollutants are applied
      in i.e. oil refineries, thermoelectric that use petroleum oils and vehicular
      pollution. Among these, highlight the adsorption of contaminants by the usage of
      activated carbon fibers and activated carbon, which are characterized by high
      surface area and uniform distribution of pores, providing appropriate conditions
      for application in processes of removing environmental contaminants. In the
      present work, activated viscose fibers (AVF) were prepared and applied in
      adsorption experiments of NO and SO2. The materials produced showed high values
      of surface area, with a predominance of micro pores with diameters in the range
      of 1.0 nm. The AVF had satisfactory performance in the removal of contaminants
      and are compatible with other synthetic fibers. Thus, the formation of active
      sites of carbon provides contaminants adsorption, demonstrating that carbon
      fibers cloth can be applied for the removal of pollutants. 

PMID- 25993358
TI  - Study of digoxin use in a public health unit.
AB  - Digoxin is used for heart failure associated to systolic dysfunction and high
      ventricular rate. It has a narrow therapeutic range and intoxication may occur
      due to drug interactions or comorbidities. The aim of this work was to study
      digoxin use in a public health unit delineating the profile of patients
      susceptible to digitalis intoxication. Medical records belonging to patients
      admitted to the cardiomyopathy ward of the health unit (2009-2010) and in use of
      digoxin were analyzed. Among 647 patients admitted, 185 individuals using digoxin
      and possessed records available. The registration of plasma digoxin concentration
      was found in 80 records and it was out of the therapeutic range in 42 patients
      (52.5%). This group of individuals was constituted mainly by males patients
      (79%), functional class III of heart failure (65%), exhibiting renal failure
      (33%). The evaluated sample reflects the epidemiology of heart failure in Brazil
      and, although pharmacotherapy had been according to Brazilian Guidelines,
      apparently the monitoring was not performed as recommended. This work highlighs
      the necessity of plasma digoxin constant monitoring during pharmacotherapy and
      the development of protocols that enable a safer use, especially in male
      patients, functional class III and with renal dysfunction. 

PMID- 25993359
TI  - Hemagglutinating/Hemolytic activities in extracts of marine invertebrates from
      the Brazilian coast and isolation of two lectins from the marine sponge Cliona
      varians and the sea cucumber Holothuria grisea.
AB  - Twenty species of marine invertebrates from the Brazilian coast were screened for
      hemagglutinating/hemolytic activity. In at least twelve tested species,
      hemagglutinating activity was different for different blood types, suggesting the
      presence of lectins. Extracts from four species showed hemolytic activity. Two
      new lectins were purified from the marine sponge Cliona varians (CvL-2) and sea
      cucumber Holothuria grisea (HGL). CvL-2 was able to agglutinate rabbit
      erythrocytes and was inhibited by galactosides. The hemagglutinating activity was
      optimal in pH neutral and temperatures below 70  degrees C. CvL-2 is a trimeric
      protein with subunits of 175 kDa. On the other hand, HGL showed both
      hemagglutinating and hemolytic activity in human and rabbit erythrocytes, but
      hemolysis could be inhibited by osmotic protection, and agglutination was
      inhibited by mucin. HGL was stable in pH values ranging from 4 to 10 and
      temperatures up to 90  degrees C. In electrophoresis and gel filtration, HGL was
      a monomeric protein with 15 kDa. CvL-2 and HGL showed different levels of
      toxicity to Artemia naplii. CvL-2 showed LC50 of 850.1 MUg/mL, whereas HGL showed
      LC50 of 9.5 ug/mL. 

PMID- 25993360
TI  - Mangroves Response to Climate Change: A Review of Recent Findings on Mangrove
      Extension and Distribution.
AB  - Mangroves function as a natural coastline protection for erosion and inundation,
      providing important environmental services. Due to their geographical
      distribution at the continent-ocean interface, the mangrove habitat may suffer
      heavy impacts from global climate change, maximized by local human activities
      occurring in a given coastal region. This review analyzed the literature
      published over the last 25 years, on the documented response of mangroves to
      environmental change caused by global climate change, taking into consideration
      104 case studies and predictive modeling, worldwide. Most studies appeared after
      the year 2000, as a response to the 1997 IPCC report. Although many reports
      showed that the world's mangrove area is decreasing due to direct anthropogenic
      pressure, several others, however, showed that in a variety of habitats mangroves
      are expanding as a response to global climate change. Worldwide, pole ward
      migration is extending the latitudinal limits of mangroves due to warmer winters
      and decreasing the frequency of extreme low temperatures, whereas in low-lying
      coastal plains, mangroves are migrating landward due to sea level rise, as
      demonstrated for the NE Brazilian coast. Taking into consideration climate change
      alone, mangroves in most areas will display a positive response. In some areas
      however, such as low-lying oceanic islands, such as in the Pacific and the
      Caribbean, and constrained coastlines, such as the SE Brazilian coast, mangroves
      will most probably not survive. 

PMID- 25993361
TI  - Diet of the chola guitarfish, Rhinobatos percellens (Rhinobatidae), in the
      Paranagua Estuarine complex.
AB  - The chola guitarfish, Rhinobatos percellens, is one of the most-captured batoids
      on the Brazilian coast, and an important predator of benthic community. Stomachs
      from R. percellens were sampled in the Paranagua estuarine complex (March/2006 to
      March/2007 and October/2008 to September/2009). The stomachs obtained were used
      for describing the diet of R. percellens, and verifying if there are seasonal and
      ontogenetic differences in their feeding into the estuarine area. The general
      analysis showed a specialized diet with a predominance of three species in food
      contents: Leptochela serratorbita, Caridea remains and Ogyrides alphaerostris.
      Ontogenetic and seasonal analysis did not reveal significant differences in the
      food consumption. These data reveal that R. percellens is a specialist predator
      of L. serratorbita, and this food component is consumed by all size classes. 

PMID- 25993362
TI  - Investigation on the effects of guava (Psidium guajava L.) infusions on
      germination, root tips and meristematic cells of Latuca sativa.
AB  - Guava (Psidium guajava L.) is a plant often employed in popular medicine.
      Recently several studies have alerted about the toxicity of substances present in
      medicinal plants, which can pose risks to the human health. In this sense, the
      present work aimed to investigate the phytotoxic, cytotoxic and genotoxic action
      of three guava varieties - Paluma, Pedro Sato and Roxa ("purple") - on the plant
      test system Lactuca sativa L. Thus, macro- and microscopic evaluations were
      carried out for five infusion concentrations (2.5, 5.0, 10.0, 20.0 and 40.0 g.L(
      1)) prepared from each variety. Distilled water was used as negative control.
      Chromatographic and spectroscopic analysis by HPLC-PAD indicated that the
      chemical composition of the infusion of Roxa is different than that of the
      infusions of the varieties Paluma and Pedro Sato. It was observed that seed
      germination and root growth in L. sativa exposed to infusions decreased with
      increasing infusion concentration, regardless of the tested cultivar. For the
      mitotic index, no statistical differences were observed. On the other hand, a
      significant increase in the frequency of cell cycle alterations was verified,
      especially for the highest concentrations tested. The cytogenotoxic effect was
      significant. Therefore, guava should not be used indiscriminately in popular
      medicine.

PMID- 25993364
TI  - Recharge contribution to the Guarani Aquifer System estimated from the water
      balance method in a representative watershed.
AB  - The contribution of recharge to regional groundwater flow systems is essential
      information required to establish sustainable water resources management. The
      objective of this work was to determine the groundwater outflow in the Ribeirao
      da Onca Basin using a water balance model of the saturated soil zone. The basin
      is located in the outcrop region of the Guarani Aquifer System (GAS). The water
      balance method involved the determination of direct recharge values, groundwater
      storage variation and base flow. The direct recharge was determined by the water
      table fluctuation method (WTF). The base flow was calculated by the hydrograph
      separation method, which was generated by a rain-flow model supported by biweekly
      streamflow measurements in the control section. Undisturbed soil samples were
      collected at depths corresponding to the variation zone of the groundwater level
      to determine the specific yield of the soil (drainable porosity). Water balances
      were performed in the saturated zone for the hydrological years from February
      2004 to January 2007. The direct recharge ranged from 14.0% to 38.0%, and
      groundwater outflow from 0.4% to 2.4% of the respective rainfall during the same
      period. 

PMID- 25993363
TI  - Plasma nitric oxide, endothelin-1, arginase and superoxide dismutase in the
      plasma and placentae from preeclamptic patients.
AB  - The aim of this study was to determine parameters of NO metabolism in plasma and
      placenta of preeclamptic (PE) patients. It was conducted a case-control study at
      Sao Jose Hospital, Brazil. Thirty-three PE and 33 normotensive pregnant were
      included in the study. The diagnosis of PE was established in accordance with the
      definitions of American College of Obstetricians and Gynecologists. Peripheral
      venous blood and placenta samples were obtained at postpartum period. Plasma NO
      levels and SOD activity were significantly lower and endothelin-1 levels and
      arginase activity were significantly higher in PE women when compared to
      controls. None of the analyzed parameters were different in the placenta between
      groups. Our findings suggest that parameters associated with NO metabolism are
      altered only at the systemic level, but not in placenta of PE patients. 

PMID- 25993366
TI  - Correction: prevalence of vitamin d deficiency in sickle cell disease: a
      systematic review.

PMID- 25993365
TI  - Bone turnover markers for early detection of fracture healing disturbances: A
      review of the scientific literature.
AB  - Imaging techniques are the standard method for assessment of fracture healing
      processes. However, these methods are perhaps not entirely reliable for early
      detection of complications, the most frequent of these being delayed union and
      non-union. A prompt diagnosis of such disorders could prevent prolonged patient
      distress and disability. Efforts should be directed towards the development of
      new technologies for improving accuracy in diagnosing complications following
      bone fractures. The variation in the levels of bone turnover markers (BTMs) have
      been assessed with regard to there ability to predict impaired fracture healing
      at an early stage, nevertheless the conclusions of some studies are not
      consensual. In this article the authors have revised the potential of BTMs as
      early predictors of prognosis in adult patients presenting traumatic bone
      fractures but who did not suffer from osteopenia or postmenopausal osteoporosis.
      The available information from the different studies performed in this field was
      systematized in order to highlight the most promising BTMs for the assessment of
      fracture healing outcome. 

PMID- 25993367
TI  - Providing enhanced care in communities.

PMID- 25993368
TI  - Twitter triumph: connect, communicate, and learn.

PMID- 25993369
TI  - Community matrons' experience as independent prescribers.
AB  - Community matrons prescribe medications and treatments for arguably the most
      complex patients in the community setting, yet little is known about their
      experiences of prescribing. Drug events and inappropriate prescribing are known
      to account for around 16% of hospital admissions. With a remit of reducing
      unplanned admissions to hospital, it is important to understand community
      matrons' experiences as prescribers and to examine the role of prescribing in
      fulfilling this agenda with consideration given to the adequacy of the
      prescribing support available. In this study, a qualitative research design was
      used and a purposive sample of seven community matrons from the south of England
      took part in the study. Semi-structured interviews were carried out and analysed
      using Braun and Clarke's six phases of thematic analysis. The findings show that
      community matrons consider prescribing-related knowledge to be essential in
      fulfilling their role and that the ability to prescribe speeds patient access to
      medicines. In some instances it may be instrumental in preventing hospital
      admission. Community matrons prescribe a limited range of medicines regularly,
      while referring to GPs for other prescribing that they consider outside their
      competency. Community matron prescribers mostly access their support from GPs and
      this is considered adequate in supporting them in their prescribing role. 

PMID- 25993370
TI  - Diagnosing and treating urinary tract infections in older people.
AB  - Even though diagnosing and treating urinary tract infections (UTIs) in older
      people can be difficult, it is essential to prevent reduction in the patients'
      wellbeing. Near-patient testing can be useful, but guidelines on this discuss the
      use of urine dipstick testing and laboratory culture in some detail. In addition,
      there are significant differences in the management of males and females, those
      with recurrent infections, and those with catheters. Community nurses are well
      placed to assess and manage this common condition, implementing correct treatment
      and resolution, owing to the close relationships they cultivate with service
      users. This article discusses the diagnosis and management of UTIs in older
      people, highlighting the differentials and red flags that need to be addressed
      urgently. 

PMID- 25993371
TI  - Managing and preventing incontinence-associated dermatitis.

PMID- 25993372
TI  - Factors influencing evidence-based practice for community nurses.
AB  - Factors influencing the development of evidence-based nursing practice (EBNP)
      were examined in Prince Edward Island, Canada. An adapted electronic
      questionnaire was distributed to practicing registered nurses and nurse
      practitioners (n=68). An analysis of variance revealed a significant difference
      between nurses' clinical practice setting and the EBNP scale. Significant
      differences were also found between age and education level when compared with
      the EBNP subscales where novice nurses were less likely to rely on experience and
      intuition, and expert nurses with a higher level of education reported being more
      skilful at synthesising and applying information from research findings into
      their nursing practice. 

PMID- 25993373
TI  - The IMPROVE-IT study and ezetimibe.

PMID- 25993374
TI  - Reducing costs and avoiding hospital admissions: can mobile working help?
AB  - The UK has an increased length of hospital stay in comparison with other European
      countries, and the need for further investment in community services is required
      if patients are to truly receive care closer to home. The increase in hospital
      admissions over the last few years may be attributed to the ageing UK population,
      as well as poor management of long-term conditions. This may be due to variations
      in the service provision and availability of case managers and community matrons.
      The poor working relationships and fragmentation of health and social care
      services remain a significant issue, despite renewed calls to improve integrated
      working, which is considered fundamental to achieving a reduction in avoidable
      hospital admissions. Mobile working was introduced in the NHS to help reform
      community health-care practice and improve continuity of care. Among other
      things, it provides clinicians with access to electronic patient records in real
      time, thus helping to reduce delays in treatment. However, we have to bear in
      mind that a number of factors could hinder the reduction in hospital admissions. 

PMID- 25993375
TI  - Understanding the Code: working in partnership.
AB  - In his continuing series looking at the law underpinning the standards set out in
      the revised Code ( NMC, 2015 ), Richard Griffith considers standard 2, which
      requires district nurses to work in partnership with the people in their care.
      Although the right to self-determination and the requirement for consent has been
      a legal principle in health care for over 100 years, its emphasis has been on
      providing a defence for health professionals rather than promoting partnership in
      the district nurse-patient relationship. Recent developments in policy and law
      have begun to herald a change in emphasis from 'health professional knows best'
      to a more patient-focused approach to decisions about care and treatment. 

PMID- 25993376
TI  - Depression and mental health in the community and the role of the nurse.
AB  - Aysha Mendes discusses the risk of depression in patients who live alone, are
      elderly, or who are coping with physical illness, and the importance of community
      nurses quickly and correctly diagnosing any symptoms. 

PMID- 25993377
TI  - Dying matters: you asked, I answered.

PMID- 25993378
TI  - Form and function: integrated care.

PMID- 25993379
TI  - Increasing pulmonary artery pulsatile flow improves hypoxic pulmonary
      hypertension in piglets.
AB  - Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary
      arteries (PA). These arteries are deformed, leading to right ventricular failure.
      Current treatments are limited. Physiologically, pulsatile blood flow is
      detrimental to the vasculature. In response to sustained pulsatile stress,
      vessels release nitric oxide (NO) to induce vasodilation for self-protection.
      Based on this observation, this study developed a protocol to assess whether an
      artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease
      in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia
      for 3 weeks and compared to a control group of piglets. Once a week, the piglets
      underwent echocardiography to assess PAH severity. At the end of hypoxia
      exposure, the piglets were subjected to a pulsatile protocol using a pulsatile
      catheter. After being anesthetized and prepared for surgery, the jugular vein of
      the piglet was isolated and the catheter was introduced through the right atrium,
      the right ventricle and the pulmonary artery, under radioscopic control.
      Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1)
      and 30 min after (T2) the pulsatile protocol. It was demonstrated that this
      pulsatile protocol is a safe and efficient method of inducing a significant
      reduction in mean PAP via an NO-dependent mechanism. These data open up new
      avenues for the clinical management of PAH. 

PMID- 25993380
TI  - Fluorescent-protein stabilization and high-resolution imaging of cleared, intact
      mouse brains.
AB  - In order to observe and quantify long-range neuronal connections in intact mouse
      brain by light microscopy, it is first necessary to clear the brain, thus
      suppressing refractive-index variations. Here we describe a method that clears
      the brain and preserves the signal from proteinaceous fluorophores using a pH
      adjusted non-aqueous index-matching medium. Successful clearing is enabled
      through the use of either 1-propanol or tert-butanol during dehydration whilst
      maintaining a basic pH. We show that high-resolution fluorescence imaging of
      entire, structurally intact juvenile and adult mouse brains is possible at
      subcellular resolution, even following many months in clearing solution. We also
      show that axonal long-range projections that are EGFP-labelled by modified Rabies
      virus can be imaged throughout the brain using a purpose-built light-sheet
      fluorescence microscope. To demonstrate the viability of the technique, we
      determined a detailed map of the monosynaptic projections onto a target cell
      population in the lateral entorhinal cortex. This example demonstrates that our
      method permits the quantification of whole-brain connectivity patterns at the
      subcellular level in the uncut brain. 

PMID- 25993382
TI  - Adsorbed Mass of Polymers on Self-Assembled Monolayers: Effect of Surface
      Chemistry and Polymer Charge.
AB  - The adsorbed mass of polymers on surfaces with different chemistry is presented,
      and the related adsorption mechanism is discussed. Strong and weak
      polyelectrolytes of negative and positive charge are studied, as well as an
      uncharged polymer. Self-assembled monolayers of alkanethiols on gold are used in
      reflectometry and quartz crystal microbalance (QCM-D) experiments as adsorbing
      substrates bearing different terminal moieties, namely, methyl, hydroxyl,
      carboxyl, and amine groups. The various polymer-surface combinations allow the
      systematic investigation of the role of surface chemistry and polymer charge on
      adsorbed amount. Interactions of different nature and range drive polymer
      adsorption: the measured adsorbed amounts reveal information about their relative
      contribution. When electrostatic chain-surface attraction is present, the largest
      adsorbed masses are observed. However, significant mass is measured even when an
      electrostatic barrier to adsorption is present, suggesting the importance of
      forces of nonelectrostatic origin, which include both hydrophobic interactions
      and specific forces acting at short distances. This mechanism results in large
      adsorbed amounts for the adsorption of weak polyelectrolytes, and it is apparent
      especially in the adsorption behavior of a neutral polymer. 

PMID- 25993381
TI  - Detection of Acute HIV-1 Infection by RT-LAMP.
AB  - A rapid, cost-effective diagnostic test for the detection of acute HIV-1
      infection is highly desired. Isothermal amplification techniques, such as reverse
      transcription loop-mediated isothermal amplification (RT-LAMP), exhibit
      characteristics that are ideal for the development of a rapid nucleic acid
      amplification test (NAAT) because they are quick, easy to perform and do not
      require complex, dedicated equipment and laboratory space. In this study, we
      assessed the ability of the HIV-1 RT-LAMP assay to detect acute HIV infection as
      compared to a representative rapid antibody test and several FDA-approved
      laboratory-based assays. The HIV-1 RT-LAMP assay detected seroconverting
      individuals one to three weeks earlier than a rapid HIV antibody test and up to
      two weeks earlier than a lab-based antigen/antibody (Ag/Ab) combo enzyme
      immunoassay (EIA). RT-LAMP was not as sensitive as a lab-based qualitative RNA
      assay, which could be attributed to the significantly smaller nucleic acid input
      volume. To our knowledge, this is the first demonstration of detecting acute HIV
      infection using the RT-LAMP assay. The availability of a rapid NAAT, such as the
      HIV-1 RT-LAMP assay, at the point of care (POC) or in laboratories that do not
      have access to large platform NAAT could increase the percentage of individuals
      who receive an acute HIV infection status or confirmation of their HIV status,
      while immediately linking them to counseling and medical care. In addition, early
      knowledge of HIV status could lead to reduced high-risk behavior at a time when
      individuals are at a higher risk for transmitting the virus. 

PMID- 25993383
TI  - Application of the DNA-specific stain methyl green in the fluorescent labeling of
      embryos.
AB  - Methyl green has long been known as a histological stain with a specific affinity
      for DNA, although its fluorescent properties have remained unexplored until
      recently. In this article, we illustrate the method for preparing a methyl green
      aqueous stock solution, that when diluted can be used as a very convenient
      fluorescent nuclear label for fixed cells and tissues. Easy procedures to label
      whole zebrafish and chick embryos are detailed, and examples of images obtained
      shown. Methyl green is maximally excited by red light, at 633 nm, and emits with
      a relatively sharp spectrum that peaks at 677 nm. It is very inexpensive, non
      toxic, highly stable in solution and very resistant to photobleaching when bound
      to DNA. Its red emission allows for unaltered high resolution scanning confocal
      imaging of nuclei in thick specimens. Finally, this methyl green staining
      protocol is compatible with other cell staining procedures, such as antibody
      labeling, or actin filaments labeling with fluorophore-conjugated phalloidin. 

PMID- 25993384
TI  - The Reach of the 340B Drug Pricing Program.

PMID- 25993386
TI  - Rationale and Design of the Balanced Anesthesia Study: A Prospective Randomized
      Clinical Trial of Two Levels of Anesthetic Depth on Patient Outcome After Major
      Surgery.
AB  - BACKGROUND: An association between relatively deep anesthesia, as guided by the
      bispectral index (BIS), and increased postoperative mortality has been
      demonstrated in 6 of 8 published observational studies, but association does not
      necessarily mean causality. Small clinical trials of anesthetic depth have
      demonstrated increased delirium and postoperative cognitive dysfunction in
      patients who were relatively deeply anesthetized, but have been inadequately
      powered to study mortality. A large-scale randomized study is required to
      determine whether causality exists. METHODS: The primary hypothesis of our study
      is that "light" anesthesia, defined as a BIS target of 50, will reduce all-cause
      mortality within 1 year of surgery in comparison with "deep" anesthesia, defined
      as a BIS target of 35, in patients aged >=60 years presenting for major surgery
      under general anesthesia. The trial is an international multicenter, randomized,
      parallel-group, double-blind (patients and investigators) prospective, intention
      to-treat, safety and efficacy study. The relative reduction in mortality in the
      light anesthesia group is expected to be 20%, giving an absolute risk reduction
      from 10% to 8%. Power analysis using a = 0.049 and b = 0.2 indicates that 3250
      patients are required in each group. RESULTS: The study is underway, and 1325
      patients have been recruited in 40 centers in 5 countries. It is anticipated that
      the study will be completed in 3 years. CONCLUSIONS: This randomized controlled
      trial should definitively answer the question of whether titrating anesthetic
      depth makes a difference to patient outcome in a vulnerable patient group.

PMID- 25993388
TI  - The Relationship of Body Mass Index with the Incidence of Postdural Puncture
      Headache in Parturients.
AB  - BACKGROUND: Unintentional dural puncture is a known risk after epidural or
      combined spinal-epidural procedures, occurring in approximately 1% of labor
      epidural catheters placed in parturients with normal body habitus but may be as
      high as 4% in morbidly obese parturients. Anecdotal experience and limited
      publications suggest that an inverse relationship between body mass index (BMI)
      and postdural puncture headache (PDPH) may exist. We hypothesized that
      parturients with increased BMI have a lower incidence of PDPH than those with a
      lower BMI after unintentional dural puncture. METHODS: After IRB approval, we
      performed a retrospective cohort study by medical record review. Case logs from
      our institution were searched for patients with documented unintentional dural
      puncture during attempted neuraxial analgesia between January 1, 2004, and
      December 13, 2013. The primary outcome was the incidence of PDPH. The association
      between BMI and PDPH was assessed using binary logistic regression, and the
      Wilcoxon-Mann-Whitney odds and confidence intervals (CIs) for a random pair of
      BMI values from a PDPH subject compared with a non-PDPH subject were calculated
      from the area under the receiver operator characteristics curve. Classification
      tree analysis was used to determine the BMI cutoff value for the risk of
      developing a PDPH. The presence or absence of second-stage labor pushing and
      placement of an intrathecal catheter after unintentional dural puncture were
      compared in parturients with and without PDPH using the Fisher exact test. BMI
      groups were dichotomized at the cutoff value (low and high BMI groups). We
      compared the incidence of a PDPH between high and low BMI groups using the Fisher
      exact test after controlling for pushing during labor and placement of an
      intrathecal catheter at the time of unintentional dural puncture. Secondary
      analysis evaluated the highest reported numeric rating of pain scores for
      headache and the need for an epidural blood patch between BMI groups. RESULTS:
      Unintentional dural puncture was identified in 518 (0.53%) patients (95% CI,
      0.48%-0.58%). The overall incidence of PDPH after unintentional dural puncture
      was 51% (95% CI, 46%-55%). The Wilcoxon-Mann-Whitney odds for a random pair of
      BMI values from a PDPH subject compared with a non-PDPH subject was 0.74 (95% CI,
      0.60-0.90, P = 0.001). The odds ratio for developing a PDPH in women who pushed
      during delivery was 2.4 (95% CI, 1.2-3.9, P = 0.001) compared with women who did
      not push. Classification tree analysis identified a BMI cutoff value of 31.5 kg/m
      for prediction of a PDPH. The incidence of PDPH in parturients with a BMI >=31.5
      kg/m (39%) was lower than in parturients with a BMI <31.5 kg/m (56%; difference 
      17%; 95% CI, -7% to -26%, P = 0.0004). The odds ratio for a PDPH in the high BMI
      compared with the low BMI group was 0.36 (95% CI, 0.14-0.92, P = 0.04) in
      parturients who pushed during labor and 0.62 (95% CI, 0.41-0.97, P = 0. 04) in
      parturients who did not push. After the unintentional dural puncture, 112 (22%)
      parturients had an intrathecal catheter placed. The incidence of PDPH in
      parturients with an intrathecal catheter was 59% (95% CI, 49%-68%) compared with
      48% (95% CI, 43%-54%) in women with an epidural catheter (P = 0.06). Median
      (interquartile range) headache severity (0-10 verbal rating scale) was 8 (6-9)
      and did not differ between parturients in the high versus low BMI groups (P =
      0.61). The rate of epidural blood patch administration for PDPH treatment was
      similar in BMI groups (difference -12%; 95% CI, 4 to -27, P = 0.13). CONCLUSIONS:
      The findings are consistent with previous reports of decreased PDPH incidence
      after unintentional dural puncture in parturients with an increased BMI, even
      after controlling for pushing during labor. Severity of headache and need for
      epidural blood patch treatment were similar in low and high BMI groups.

PMID- 25993387
TI  - Monitoring cerebral autoregulation after brain injury: multimodal assessment of
      cerebral slow-wave oscillations using near-infrared spectroscopy.
AB  - BACKGROUND: Continuous monitoring of cerebral autoregulation might provide novel
      treatment targets and identify therapeutic windows after acute brain injury. Slow
      oscillations of cerebral hemodynamics (0.05-0.003 Hz) are visible in multimodal
      neuromonitoring and may be analyzed to provide novel, surrogate measures of
      autoregulation. Near-infrared spectroscopy (NIRS) is an optical neuromonitoring
      technique, which shows promise for widespread clinical applicability because it
      is noninvasive and easily delivered across a wide range of clinical scenarios.
      The aim of this study is to identify the relationship between NIRS signal
      oscillations and multimodal neuromonitoring, examining the utility of near
      infrared derived indices of cerebrovascular reactivity. METHODS: Twenty-seven
      sedated, ventilated, brain-injured patients were included in this observational
      study. Intracranial pressure, transcranial Doppler-derived flow velocity in the
      middle cerebral artery, and ipsilateral cerebral NIRS variables were continuously
      monitored. Signals were compared using wavelet measures of phase and coherence to
      examine the spectral features involved in reactivity index calculations.
      Established indices of autoregulatory reserve such as the pressure reactivity
      index (PRx) and mean velocity index (Mx) and the NIRS indices such as total
      hemoglobin reactivity index (THx) and tissue oxygen reactivity index (TOx) were
      compared using correlation and Bland-Altman analysis. RESULTS: NIRS indices
      correlated significantly between PRx and THx (rs = 0.63, P < 0.001), PRx and TOx
      (r = 0.40, P = 0.04), and Mx and TOx (r = 0.61, P = 0.004) but not between Mx and
      THx (rs = 0.26, P = 0.28) and demonstrated wide limits between these variables:
      PRx and THx (bias, -0.06; 95% limits, -0.44 to 0.32) and Mx and TOx (bias, +0.15;
      95% limits, -0.34 to 0.64). Analysis of slow-wave activity throughout the
      intracranial pressure, transcranial Doppler, and NIRS recordings revealed
      statistically significant interrelationships, which varied dynamically and were
      nonsignificant at frequencies <0.008 Hz. CONCLUSIONS: Although slow-wave activity
      in intracranial pressure, transcranial Doppler, and NIRS is significantly
      similar, it varies dynamically in both time and frequency, and this manifests as
      incomplete agreement between reactivity indices. Analysis informed by a priori
      knowledge of physiology underpinning NIRS variables combined with sophisticated
      analysis techniques has the potential to deliver noninvasive surrogate measures
      of autoregulation, guiding therapy.

PMID- 25993389
TI  - Preoperative Aspirin Use and Lung Injury After Aortic Valve Replacement Surgery:
      A Retrospective Cohort Study.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) occurs uncommonly after
      cardiac surgery but has a mortality rate as high as 80%. Aspirin may prevent lung
      injury in at-risk patients by reducing platelet-neutrophil aggregates in the
      lung. We hypothesized that preoperative aspirin use would be associated with a
      decreased risk of ARDS after aortic valve replacement surgery. METHODS: We
      performed a retrospective single-center cohort study that included all adult
      patients who had aortic valve replacement surgery during a 5-year period. The
      primary outcome variable was postoperative ARDS. The secondary outcome variable
      was nadir PaO2/FIO2 ratio during the first 72 hours after surgery. Both crude and
      propensity score-adjusted logistic regression analyses were performed to estimate
      the odds ratio for developing ARDS in aspirin users. Subgroups were analyzed to
      determine whether preoperative aspirin use might be associated with improved
      oxygenation in patients with specific risk factors for lung injury. RESULTS: Of
      the 375 patients who had aortic valve replacement surgery during the study
      period, 181 patients took aspirin preoperatively (48.3%) with most taking a dose
      of 81 mg (72.0%). There were 22 cases of ARDS in the cohort (5.5%). There was no
      significant difference in the rate of ARDS between aspirin users and nonusers
      (5.0% vs 6.7%, P = 0.52). There was also no significant difference in the nadir
      PaO2/FIO2 ratio between aspirin users and nonusers (P = 0.12). The crude odds
      ratio for ARDS in aspirin users was 0.725 (99% confidence interval, 0.229-2.289;
      P = 0.47), and the propensity score-adjusted odds ratio was 0.457 (99% confidence
      interval, 0.120-1.730; P = 0.13). CONCLUSIONS: Within the constraints of this
      analysis that included only 22 affected patients, preoperative aspirin use was
      not associated with a decreased incidence of ARDS after aortic valve replacement
      surgery or improved oxygenation.

PMID- 25993390
TI  - Predictors of Delayed Postoperative Respiratory Depression Assessed from Naloxone
      Administration.
AB  - BACKGROUND: The aim of this study was to identify patient and procedural
      characteristics associated with postoperative respiratory depression or sedation
      requiring naloxone intervention. METHODS: We identified patients who received
      naloxone to reverse opioid-induced respiratory depression or sedation within 48
      hours after discharge from anesthetic care (transfer from the postanesthesia care
      unit or transfer from the operating room to postoperative areas) between July 1,
      2008, and June 30, 2010. Patients were matched to 2 control subjects based on
      age, sex, and exact type of procedure performed during the same year. A chart
      review was performed to identify patient, anesthetic, and surgical factors that
      may be associated with risk for intervention requiring naloxone. In addition, we
      identified all patients who developed adverse respiratory events
      (hypoventilation, apnea, oxyhemoglobin desaturation, pain/sedation mismatch)
      during phase 1 anesthesia recovery. We performed conditional logistic regression
      taking into account the 1:2 matched set case-control study design to assess
      patient and procedural characteristics associated with naloxone use. RESULTS: We
      identified 134 naloxone administrations, 58% within 12 hours of discharge from
      anesthesia care, with an incidence of 1.6 per 1000 (95% confidence interval [CI],
      1.3-1.9) anesthetics. The presence of obstructive sleep apnea (odds ratio [OR] =
      2.45; 95% CI, 1.27-4.66; P = 0.008) and diagnosis of an adverse respiratory event
      in the postanesthesia recovery room (OR = 5.11; 95% CI, 2.32-11.27; P < 0.001)
      were associated with an increased risk for requiring naloxone to treat
      respiratory depression or sedation after discharge from anesthesia care. After
      discharge from anesthesia care, patients administered naloxone used a greater
      median dose of opioids (10 [interquartile range, 0-47.1] vs 5 [0-24.8] IV
      morphine equivalents, P = 0.020) and more medications with sedating side effects
      (n = 41 [31%] vs 24 [9%]; P < 0.001). CONCLUSIONS: Obstructive sleep apnea and
      adverse respiratory events in the recovery room are harbingers of increased risk
      for respiratory depression or sedation requiring naloxone after discharge from
      anesthesia care. Also, patients administered naloxone received more opioids and
      other sedating medications after discharge from anesthetic care. Our findings
      suggest that these patients may benefit from more careful monitoring after being
      discharged from anesthesia care.

PMID- 25993391
TI  - Treadmill training combined with insulin suppresses diabetic nerve pain and
      cytokines in rat sciatic nerve.
AB  - BACKGROUND: Insulin therapy plays a critical role in managing type 1 diabetes
      mellitus, and exercise produces alterations in pain sensation. This experiment
      explored the effects of insulin therapy combined with treadmill training on
      diabetic neuropathic pain and on the expression of malondialdehyde (MDA) and
      cytokines. METHODS: Rats were given 4 weeks of insulin (100 IU/kg) therapy and
      treadmill training (30-60 min/d of training at 20-25 m/min) each day beginning on
      day 3 after streptozotocin (65 mg/kg, IV) injection and continuing until day 27.
      Sensitivity to heat and mechanical stimuli and the expression of interleukin (IL)
      10, IL-6, tumor necrosis factor-alpha, and MDA in the sciatic nerve were
      estimated. RESULTS: We showed that 2 to 4 weeks of treadmill training, insulin
      treatment, or their combination increased both paw withdrawal thresholds and
      latencies compared with the same regimen in sedentary diabetic rats (all P <
      0.0022). Treatment with insulin, but without treadmill training, had significant
      effects on glycemic control (P < 0.0001) and restored body weight (P < 0.0001) in
      the diabetic rats. The diabetic rats demonstrated the upregulation (all P <
      0.009) of IL-6, MDA, and tumor necrosis factor-alpha in the sciatic nerve on days
      14 and 28 after streptozotocin treatment, whereas in diabetic rats receiving
      insulin, treadmill training, or a combination (all P < 0.01), this upregulation
      was decreased. Insulin, treadmill training, or the combination increased IL-10
      expression (all P < 0.0051) in all diabetic rats. CONCLUSIONS: Treadmill training
      combined with insulin therapy showed the best improvements in tactile allodynia
      and thermal hyperalgesia among our 3 treatment groups. The benefits of insulin
      intervention and treadmill training could be related to chronic inflammation
      (proinflammatory cytokines) and oxidative stress (MDA).

PMID- 25993392
TI  - Involvement of Opioid Receptors in the Lipid Rescue of Bupivacaine-Induced
      Cardiotoxicity.
AB  - BACKGROUND: Lipid emulsion (LE) has been successfully used for resuscitation of
      local anesthetic cardiotoxicity caused by bupivacaine overdose. Opioid receptors
      have been shown to play a key role in cardio protection. We explored whether this
      rescue action of LE is mediated through opioid receptors. METHODS: Asystole was
      induced by bupivacaine (10 mg/kg over 20 seconds, IV) in young male Sprague
      Dawley rats, and resuscitation with LE (intralipid 20%; 5 mL/kg bolus and 0.5
      mL/kg/min maintenance) was started immediately. The rats were pretreated 2
      minutes before inducing asystole with nonselective opioid receptor antagonists
      such as naloxone and naloxone methiodide, as well as highly selective opioid
      receptor antagonists for subtype kappa, delta, and u or phosphate buffer solution
      as a control. Heart rates and ejection fractions were measured using
      echocardiography. RESULTS: LE rescue of bupivacaine cardiotoxicity was prevented
      by high-dose (1 mg/kg) naloxone but not by lower doses of naloxone (1, 5, and 10
      ug/kg), by naloxone methiodide (which does not cross the blood-brain barrier),
      and by a selective delta- and kappa-opioid receptor antagonists at a higher (10
      mg/kg) dose. Successful LE rescue was not affected by highly selective u-opioid
      receptor antagonists. delta-Opioid receptor antagonist (10 mg/kg) pretreatment
      also resulted in reduced phosphorylation level of cardiac glycogen synthase
      kinase-3beta in rats that were not resuscitated by LE compared with control.
      CONCLUSIONS: Our data highlight the involvement of peripheral delta- and kappa
      opioid receptors in the rescue action of LE.

PMID- 25993393
TI  - Transcriptome sequencing of three Ranunculus species (Ranunculaceae) reveals
      candidate genes in adaptation from terrestrial to aquatic habitats.
AB  - Adaptation to aquatic habitats is a formidable challenge for terrestrial
      angiosperms that has long intrigued scientists. As part of a suite of work to
      explore the molecular mechanism of adaptation to aquatic habitats, we here
      sequenced the transcriptome of the submerged aquatic plant Ranunculus bungei, and
      two terrestrial relatives R. cantoniensis and R. brotherusii, followed by
      comparative evolutionary analyses to determine candidate genes for adaption to
      aquatic habitats. We obtained 126,037, 140,218 and 114,753 contigs for R. bungei,
      R. cantoniensis and R. brotherusii respectively. Bidirectional Best Hit method
      and OrthoMCL method identified 11,362 and 8,174 1:1:1 orthologous genes (one
      ortholog is represented in each of the three species) respectively. Non
      synonymous/synonymous (dN/dS) analyses were performed with a maximum likelihood
      method and an approximate method for the three species-pairs. In total, 14 genes
      of R. bungei potentially involved in the adaptive transition from terrestrial to
      aquatic habitats were identified. Some of the homologs to these genes in model
      plants are involved in vacuole protein formation, regulating 'water transport
      process' and 'microtubule cytoskeleton organization'. Our study opens the door to
      understand the molecular mechanism of plant adaptation from terrestrial to
      aquatic habitats. 

PMID- 25993395
TI  - Functional Profiling of 2-Aminopyrimidine Histamine H4 Receptor Modulators.
AB  - Histamine is an important endogenous signaling molecule that is involved in a
      number of physiological processes including allergic reactions, gastric acid
      secretion, neurotransmitter release, and inflammation. The biological effects of
      histamine are mediated by four histamine receptors with distinct functions and
      distribution profiles (H1-H4). The most recently discovered histamine receptor
      (H4) has emerged as a promising drug target for treating inflammatory diseases. A
      detailed understanding of the role of the H4 receptor in human disease remains
      elusive, in part because low sequence similarity between the human and rodent H4
      receptors complicates the translation of preclinical pharmacology to humans. This
      review provides an overview of H4 drug discovery programs that have studied cross
      species structure-activity relationships, with a focus on the functional
      profiling of the 2-aminopyrimidine chemotype that has advanced to the clinic for
      allergy, atopic dermatitis, asthma, and rheumatoid arthritis. 

PMID- 25993394
TI  - Quantification of neurovascular protection following repetitive hypoxic
      preconditioning and transient middle cerebral artery occlusion in mice.
AB  - Experimental animal models of stroke are invaluable tools for understanding
      stroke pathology and developing more effective treatment strategies. A 2 week
      protocol for repetitive hypoxic preconditioning (RHP) induces long-term
      protection against central nervous system (CNS) injury in a mouse model of focal
      ischemic stroke. RHP consists of 9 stochastic exposures to hypoxia that vary in
      both duration (2 or 4 hr) and intensity (8% and 11% O2). RHP reduces infarct
      volumes, blood-brain barrier (BBB) disruption, and the post-stroke inflammatory
      response for weeks following the last exposure to hypoxia, suggesting a long-term
      induction of an endogenous CNS-protective phenotype. The methodology for the dual
      quantification of infarct volume and BBB disruption is effective in assessing
      neurovascular protection in mice with RHP or other putative neuroprotectants.
      Adult male Swiss Webster mice were preconditioned by RHP or duration-equivalent
      exposures to 21% O2 (i.e. room air). A 60 min transient middle cerebral artery
      occlusion (tMCAo) was induced 2 weeks following the last hypoxic exposure. Both
      the occlusion and reperfusion were confirmed by transcranial laser Doppler
      flowmetry. Twenty-two hr after reperfusion, Evans Blue (EB) was intravenously
      administered through a tail vein injection. 2 hr later, animals were sacrificed
      by isoflurane overdose and brain sections were stained with 2,3,5-
      triphenyltetrazolium chloride (TTC). Infarcts volumes were then quantified. Next,
      EB was extracted from the tissue over 48 hr to determine BBB disruption after
      tMCAo. In summary, RHP is a simple protocol that can be replicated, with minimal
      cost, to induce long-term endogenous neurovascular protection from stroke injury
      in mice, with the translational potential for other CNS-based and systemic pro
      inflammatory disease states. 

PMID- 25993396
TI  - Ab initio RNA folding.
AB  - RNA molecules are essential cellular machines performing a wide variety of
      functions for which a specific three-dimensional structure is required. Over the
      last several years, the experimental determination of RNA structures through x
      ray crystallography and NMR seems to have reached a plateau in the number of
      structures resolved each year, but as more and more RNA sequences are being
      discovered, the need for structure prediction tools to complement experimental
      data is strong. Theoretical approaches to RNA folding have been developed since
      the late nineties, when the first algorithms for secondary structure prediction
      appeared. Over the last 10 years a number of prediction methods for 3D structures
      have been developed, first based on bioinformatics and data-mining, and more
      recently based on a coarse-grained physical representation of the systems. In
      this review we are going to present the challenges of RNA structure prediction
      and the main ideas behind bioinformatic approaches and physics-based approaches.
      We will focus on the description of the more recent physics-based
      phenomenological models and on how they are built to include the specificity of
      the interactions of RNA bases, whose role is critical in folding. Through
      examples from different models, we will point out the strengths of physics-based
      approaches, which are able not only to predict equilibrium structures, but also
      to investigate dynamical and thermodynamical behavior, and the open challenges to
      include more key interactions ruling RNA folding.

PMID- 25993397
TI  - Indirect Band Gap Emission by Hot Electron Injection in Metal/MoS2 and Metal/WSe2
      Heterojunctions.
AB  - Transition metal dichalcogenides (TMDCs), such as MoS2 and WSe2, are free of
      dangling bonds and therefore make more "ideal" Schottky junctions than bulk
      semiconductors, which produce Fermi energy pinning and recombination centers at
      the interface with bulk metals, inhibiting charge transfer. Here, we observe a
      more than 10* enhancement in the indirect band gap photoluminescence of
      transition metal dichalcogenides (TMDCs) deposited on various metals (e.g., Cu,
      Au, Ag), while the direct band gap emission remains unchanged. We believe the
      main mechanism of light emission arises from photoexcited hot electrons in the
      metal that are injected into the conduction band of MoS2 and WSe2 and
      subsequently recombine radiatively with minority holes in the TMDC. Since the
      conduction band at the K-point is 0.5 eV higher than at the Sigma-point, a lower
      Schottky barrier exists for the Sigma-point band, making electron injection more
      favorable. Also, the Sigma band consists of the sulfur pz orbital, which overlaps
      more significantly with the electron wave functions in the metal. This
      enhancement in the indirect emission only occurs for thick flakes of MoS2 and
      WSe2 (>=100 nm) and is completely absent in monolayer and few-layer (~10 nm)
      flakes. Here, the flake thickness must exceed the depletion width of the Schottky
      junction, in order for efficient radiative recombination to occur in the TMDC.
      The intensity of this indirect peak decreases at low temperatures, which is
      consistent with the hot electron injection model. 

PMID- 25993398
TI  - Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast
      Cancer to Doxorubicin.
AB  - BACKGROUND: Breast cancer is a leading cause of death in women and with an
      increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based
      drug is conventional used on breast cancer clinical chemotherapy. However, the
      drug resistances limited the curative effect of the doxorubicin therapy in breast
      cancer patients, but the molecular mechanism determinants of breast cancer
      resistance to doxorubicin chemotherapy are not fully understood. In order to
      explore the association between metadherin (MTDH) and doxorubicin sensitivity,
      the differential expressions of MTDH in breast cancer cell lines and the
      sensitivity to doxorubicin of breast cancer cell lines were investigated.
      METHODS: The mRNA and protein expression of MTDH were determined by real-time PCR
      and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S,
      MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and
      overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth
      and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell
      cycle assay and apoptosis rate was determined by flow cytometry. RESULTS: MCF
      7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest
      expression of MTDH. After MTDH gene was knocked down, the cell proliferation was
      inhibited, and the inhibitory rate of cell growth and apoptosis rate were
      enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of
      doxorubicin treatment. On the other hand, the opposite results were observed in
      MDA-MB-231 cells with overexpressed MTDH gene. CONCLUSION: MTDH gene plays a
      promoting role in the proliferation of breast cancer cells and its high
      expression may be associated with doxorubicin sensitivity of breast cancer.

PMID- 25993399
TI  - The use of rapid dengue diagnostic tests in a routine clinical setting in a
      dengue-endemic area of Colombia.
AB  - There is insufficient evidence of the usefulness of dengue diagnostic tests under
      routine conditions. We sought to analyse how physicians are using dengue
      diagnostics to inform research and development. Subjects attending 14 health
      institutions in an endemic area of Colombia with either a clinical diagnosis of
      dengue or for whom a dengue test was ordered were included in the study. Patterns
      of test-use are described herein. Factors associated with the ordering of dengue
      diagnostic tests were identified using contingency tables, nonparametric tests
      and logistic regression. A total of 778 subjects were diagnosed with dengue by
      the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491
      dengue tests were ordered in subjects whose primary diagnosis was not dengue.
      Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI)
      1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year
      (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue
      tests. Dengue tests were used both to rule in and rule out diagnosis. The latter
      use is not justified by the sensitivity of current rapid dengue diagnostic tests.
      Ordering of dengue tests appear to depend on a combination of factors, including
      physician and institutional preferences, as well as other patient and
      epidemiological factors. 

PMID- 25993400
TI  - Using immunoglobulin Y as an alternative antibody for the detection of hepatitis
      A virus in frozen liver sections.
AB  - An increasing amount of research has been conducted on immunoglobulin Y (IgY)
      because the use of IgY offers several advantages with respect to diagnostic
      testing, including its easy accessibility, low cost and translatability to large
      scale production, in addition to the fact that it can be ethically produced. In a
      previous work, immunoglobulin was produced and purified from egg yolks (IgY)
      reactive to hepatitis A virus (HAV) antigens. In the present work, this anti-HAV
      specific IgY was used in an indirect immunofluorescence assay to detect viral
      antigens in liver biopsies that were obtained from experimentally infected
      cynomolgus monkeys. Fields that were positive for HAV antigen were detected in
      liver sections using confocal microscopy. In conclusion, egg yolks from immunised
      hens may be a reliable source for antibody production, which can be employed for
      immunological studies. 

PMID- 25993402
TI  - Structures, Thermochemical Properties, and Bonding of Mixed Alkaline-Earth-Metal
      Silicon Trimers Si3M(+/0/-) with M = Be, Mg, Ca.
AB  - The ground state geometries, electronic structures, and thermochemical properties
      of binary alkaline-earth-metal silicon clusters Si3M with M = Be, Mg, Ca in
      neutral, cationic, and anionic states were investigated using quantum chemical
      computations. Lowest-lying isomers of the clusters were determined on the basis
      of the composite G4 energies. Along with total atomization energies,
      thermochemical parameters were determined for the first time by means of the G4
      and coupled-cluster theory with complete basis set CCSD(T)/CBS approaches. The
      most favored equilibrium formation sequences for Si3M clusters emerge as follows:
      all Si3M(+/0/-) clusters are formed by attaching the M atom into the
      corresponding cation, neutral and anion silicon trimer Si3(+/0/-), except for the
      Si3Mg(+) and Si3Ca(+) where the metal cations are bound to the neutral Si3. The
      resulting mixed tetramers exhibit geometrical and electronic features similar to
      those of the pure silicon tetramer Si4(+/0/-). Electron localization function
      (ELF) and ring current analyses point out that the sigma-aromatic character of
      silicon tetramer remains unchanged upon substituting one Si atom by one alkaline
      earth-metal atom. 

PMID- 25993403
TI  - Microscopic nail clipping findings in patients with psoriasis.
AB  - BACKGROUND: Nail clipping microscopy is a valuable diagnostic tool in
      onychomycosis but has not been explored for the diagnosis of onychodystrophy
      caused by psoriasis. The objective of this study was to try to establish criteria
      for the diagnosis of psoriasis by this method. METHODS: Cross-sectional study of
      adult patients with clear-cut psoriasis is divided into 2 groups: (1) with
      onychodystrophy and (2) with clinically normal nails. The patients were evaluated
      regarding gender and age, among other clinical variables. The samples were coded
      to allow blinded microscopic interpretation for nail plate and subungual region
      thickness and for the presence or absence of corneocytes, neutrophils, serous
      lakes, blood, bacteria, onychokaryosis, hypereosinophilic nuclear shadows, and
      fungi. RESULTS: Ninety-six patients with psoriasis were enrolled in this study.
      There were 40 male and 56 female subjects; ages varied from 16 to 87 years (mean,
      51 years). Onychodystrophy was detected in 51 patients (53%). On average, nail
      plate thickness and subungual region thickness measured 0.44 and 0.19 mm in the
      onychodystrophy group and 0.41 and 0.14 mm in the clinically normal group (P >
      0.05). Dystrophic nails presented 4.5 layers of corneocytes, on average, in
      contrast to the average of 2.4 in the clinically normal-looking nails (P =
      0.0004). Neutrophils (12%), serous lakes (46%), blood collections (11%), bacteria
      (74%), fungi (20%), onychokaryosis, and hypereosinophilic nuclear shadows were
      all more common in the onychodystrophy group but not in a statistically
      significant standard when compared with the other group (P > 0.05). CONCLUSIONS:
      Nail clippings from patients with psoriasis present abnormally thickened
      subungual region with prominent hypercorneocytosis, serous lakes, bacteria,
      neutrophils, and blood collections. If fungi are present, usually there are
      spores. Clinically, normal-looking nails in patients with psoriasis can present
      microscopic abnormalities.

PMID- 25993401
TI  - Prevention of congenital Chagas through treatment of girls and women of
      childbearing age.
AB  - It is currently unknown whether treatment of Chagas disease decreases the risk of
      congenital transmission from previously treated mothers to their infants. In a
      cohort of women with Chagas disease previously treated with benznidazole, no
      congenital transmission of the disease was observed in their newborns. This
      finding provides support for the treatment of Chagas disease as early as
      possible. 

PMID- 25993404
TI  - Pruritic red papules on the right flank: challenge.

PMID- 25993405
TI  - Pruritic red papules of the right flank.

PMID- 25993406
TI  - Amelanotic melanoma mimicking an atypical fibrohistiocytic lesion.

PMID- 25993407
TI  - Amelanotic vulvar melanoma: a case report.
AB  - A 14-year-old girl stated that she has vulvar pruritus, pain, and bleeding and
      underwent a complete gynecological evaluation during which a suspicious 2-cm
      achromic lesion on her vulva was observed. Initially, it was suspected to be a
      pyogenic granuloma, in relation to the patient's age. A biopsy was taken, and a
      histopathological diagnosis of amelanotic mucosal melanoma was made. Pyogenic
      granuloma is a reactive hyperproliferation vascular response to trauma or other
      stimuli. It predominantly occurs in the second decade of life in young females,
      in relation to the vascular effects of female hormones. Primary mucosal melanoma
      is a rare and aggressive neoplasm, characterized by a higher aggressiveness and a
      worse prognosis than her cutaneous counterpart. The female genital tract is the
      second most common site of onset of mucosal melanoma; it represents the 3% of
      melanomas diagnosed in women. 

PMID- 25993408
TI  - 100 Years since Streeter and Phelps: It Is Time To Update the Biology in Our
      Water Quality Models.

PMID- 25993409
TI  - Hairy/Enhancer-of-Split MEGANE and Proneural MASH1 Factors Cooperate
      Synergistically in Midbrain GABAergic Neurogenesis.
AB  - GABAergic neurons are the primary inhibitory cell type in the mature brain and
      their dysfunction is associated with important neurological conditions like
      schizophrenia and anxiety. We aimed to discover the underlying mechanisms for
      dorsal/ventral midbrain GABAergic neurogenesis. Previous work by us and others
      has provided crucial insights into the key function of Mgn and Mash1 genes in
      determining GABAergic neurotransmitter fate. Induction of dorsal midbrain
      GABAergic neurons does not take place at any time during development in either of
      the single mutant mice. However, GABAergic neurons in the ventral midbrain
      remained unchanged. Thus, the similarities in MB-GABAergic phenotype observed in
      the Mgn and Mash1 single mutants suggest the existence of other factors that take
      over the function of MGN and MASH1 in the ventral midbrain or the existence of
      different molecular mechanisms. We show that this process essentially depends on
      heterodimers and homodimers formed by MGN and MASH1 and deciphered the in vivo
      relevance of the interaction by phenotypic analysis of Mgn/Mash1 double knockout
      and compound mice. Furthermore, the combination of gain- and loss-of-function
      experiments in the developing midbrain showed co-operative roles for Mgn and
      Mash1 genes in determining GABAergic identity. Transcription factors belonging to
      the Enhancer-of-split-related and proneural families have long been believed to
      counterpart each other's function. This work uncovers a synergistic cooperation
      between these two families, and provides a novel paradigm for how these two
      families cooperate for the acquisition of MB-GABAergic neuronal identity.
      Understanding their molecular mechanisms is essential for cell therapy strategies
      to amend GABAergic deficits. 

PMID- 25993410
TI  - The Hand of Cercopithecoides williamsi (Mammalia, Primates): Earliest Evidence
      for Thumb Reduction among Colobine Monkeys.
AB  - Thumb reduction is among the most important features distinguishing the African
      and Asian colobines from each other and from other Old World monkeys. In this
      study we demonstrate that the partial skeleton KNM-ER 4420 from Koobi Fora,
      Kenya, dated to 1.9 Ma and assigned to the Plio-Pleistocene colobine species
      Cercopithecoides williamsi, shows marked reduction of its first metacarpal
      relative to the medial metacarpals. Thus, KNM-ER 4420 is the first documented
      occurrence of cercopithecid pollical reduction in the fossil record. In the size
      of its first metacarpal relative to the medial metacarpals, C. williamsi is
      similar to extant African colobines, but different from cercopithecines, extant
      Asian colobines and the Late Miocene colobines Microcolobus and Mesopithecus.
      This feature clearly links the genus Cercopithecoides with the extant African
      colobine clade and makes it the first definitive African colobine in the fossil
      record. The postcranial adaptations to terrestriality in Cercopithecoides are
      most likely secondary, while ancestral colobinans (and colobines) were arboreal.
      Finally, the absence of any evidence for pollical reduction in Mesopithecus
      implies either independent thumb reduction in African and Asian colobines or
      multiple colobine dispersal events out of Africa. Based on the available
      evidence, we consider the first scenario more likely. 

PMID- 25993411
TI  - Is tuberculosis treatment really free in China? A study comparing two areas with
      different management models.
AB  - OBJECTIVE: China has implemented a free-service policy for tuberculosis. However,
      patients still have to pay a substantial proportion of their annual income for
      treatment of this disease. This study describes the economic burden on patients
      with tuberculosis; identifies related factors by comparing two areas with
      different management models; and provides policy recommendation for tuberculosis
      control reform in China. METHODS: There are three tuberculosis management models
      in China: the tuberculosis dispensary model, specialist model and integrated
      model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which
      correspond to areas implementing the integrated model and dispensary model,
      respectively. Patients diagnosed and treated for tuberculosis since January 2010
      were recruited as study subjects. A total of 590 patients (316 patients from ZJG
      and 274 patients from TX) were interviewed with a response rate of 81%. The
      economic burden attributed to tuberculosis, including direct costs and indirect
      costs, was estimated and compared between the two study sites. The Mann-Whitney U
      Test was used to compare the cost differences between the two groups. Potential
      factors related to the total out-of-pocket costs were analyzed based on a step-by
      step multivariate linear regression model after the logarithmic transformation of
      the costs. RESULTS: The average (median, interquartile range) total cost was
      18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly
      higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range:
      983-6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health
      insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY
      in TX. Based on the multivariable linear regression analysis, factors related to
      the total out-of-pocket costs were study site, age, number of clinical visits,
      residence, diagnosis delay, hospitalization, intake of liver protective drugs and
      use of the second-line drugs. CONCLUSION: Under the current "free of diagnosis
      and treatment" policy, the financial burden remains heavy on tuberculosis
      patients. Policy makers need to consider appropriate steps to lessen the burden
      of out-of-pocket costs for tuberculosis patients in China and how best to improve
      service delivery for poor patients.

PMID- 25993412
TI  - PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis
      and Poor Prognosis.
AB  - BACKGROUND: Osteosarcoma is the most frequent type of malignant bone tumor in
      children and adolescents and is associated with a high propensity for lung
      metastasis. Recent experiments have indicated that PLA2G16 contributes to
      osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell
      lines. The aim of this study was to compare the expression of PLA2G16 in non
      metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression
      can serve as a biomarker of osteosarcoma prognosis and metastasis. METHODS:
      Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary
      osteosarcoma patients (18 patients without metastases and 17 patients with
      metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on
      tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and
      survival of the patients were followed up for a minimum of 36 months and a
      maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated
      by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression
      analysis was used to identify significant independent prognostic factors.
      RESULTS: Osteosarcoma patients with metastasis showed a higher expression of
      PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did
      patients without metastasis. Osteosarcoma patients with positive IHC staining of
      PLA2G16 expression at primary sites had shorter overall survival and metastasis
      free survival (both at P values <0.02). Moreover, multivariate Cox analysis
      identified PLA2G16 expression as an independent prognostic factor to predict poor
      overall survival and metastasis-free survival (both P values < 0.03).
      CONCLUSIONS: This study indicated that PLA2G16 expression is a significant
      prognostic factor in primary osteosarcoma patients for predicting the development
      of metastases and poor survival.

PMID- 25993414
TI  - Presenting an Approach for Conducting Knowledge Architecture within Large-Scale
      Organizations.
AB  - Knowledge architecture (KA) establishes the basic groundwork for the successful
      implementation of a short-term or long-term knowledge management (KM) program. An
      example of KA is the design of a prototype before a new vehicle is manufactured.
      Due to a transformation to large-scale organizations, the traditional
      architecture of organizations is undergoing fundamental changes. This paper
      explores the main strengths and weaknesses in the field of KA within large-scale
      organizations and provides a suitable methodology and supervising framework to
      overcome specific limitations. This objective was achieved by applying and
      updating the concepts from the Zachman information architectural framework and
      the information architectural methodology of enterprise architecture planning
      (EAP). The proposed solution may be beneficial for architects in knowledge
      related areas to successfully accomplish KM within large-scale organizations. The
      research method is descriptive; its validity is confirmed by performing a case
      study and polling the opinions of KA experts. 

PMID- 25993413
TI  - Label-Free Protein-RNA Interactome Analysis Identifies Khsrp Signaling Downstream
      of the p38/Mk2 Kinase Complex as a Critical Modulator of Cell Cycle Progression.
AB  - Growing evidence suggests a key role for RNA binding proteins (RBPs) in genome
      stability programs. Additionally, recent developments in RNA sequencing
      technologies, as well as mass-spectrometry techniques, have greatly expanded our
      knowledge on protein-RNA interactions. We here use full transcriptome sequencing
      and label-free LC/MS/MS to identify global changes in protein-RNA interactions in
      response to etoposide-induced genotoxic stress. We show that RBPs have distinct
      binding patterns in response to genotoxic stress and that inactivation of the RBP
      regulator module, p38/MK2, can affect the entire spectrum of protein-RNA
      interactions that take place in response to stress. In addition to validating the
      role of known RBPs like Srsf1, Srsf2, Elavl1 in the genotoxic stress response, we
      add a new collection of RBPs to the DNA damage response. We identify Khsrp as a
      highly regulated RBP in response to genotoxic stress and further validate its
      role as a driver of the G(1/)S transition through the suppression of Cdkn1a(P21)
      transcripts. Finally, we identify KHSRP as an indicator of overall survival, as
      well as disease free survival in glioblastoma multiforme.

PMID- 25993415
TI  - Weather Variability Associated with Aedes (Stegomyia) aegypti (Dengue Vector)
      Oviposition Dynamics in Northwestern Argentina.
AB  - This study aims to develop a forecasting model by assessing the weather
      variability associated with seasonal fluctuation of Aedes aegypti oviposition
      dynamic at a city level in Oran, in northwestern Argentina. Oviposition dynamics
      were assessed by weekly monitoring of 90 ovitraps in the urban area during 2005
      2007. Correlations were performed between the number of eggs collected weekly and
      weather variables (rainfall, photoperiod, vapor pressure of water, temperature,
      and relative humidity) with and without time lags (1 to 6 weeks). A stepwise
      multiple linear regression analysis was performed with the set of meteorological
      variables from the first year of study with the variables in the time lags that
      best correlated with the oviposition. Model validation was conducted using the
      data from the second year of study (October 2006- 2007). Minimum temperature and
      rainfall were the most important variables. No eggs were found at temperatures
      below 10  degrees C. The most significant time lags were 3 weeks for minimum
      temperature and rains, 3 weeks for water vapor pressure, and 6 weeks for maximum
      temperature. Aedes aegypti could be expected in Oran three weeks after rains with
      adequate min temperatures. The best-fit forecasting model for the combined
      meteorological variables explained 70 % of the variance (adj. R(2)). The
      correlation between Ae. aegypti oviposition observed and estimated by the
      forecasting model resulted in rs = 0.80 (P < 0.05). The forecasting model
      developed would allow prediction of increases and decreases in the Ae. aegypti
      oviposition activity based on meteorological data for Oran city and, according to
      the meteorological variables, vector activity can be predicted three or four
      weeks in advance.

PMID- 25993416
TI  - Isomerization of allylbenzenes.

PMID- 25993417
TI  - Silver nanoparticles as potential antibacterial agents.
AB  - Multi-drug resistance is a growing problem in the treatment of infectious
      diseases and the widespread use of broad-spectrum antibiotics has produced
      antibiotic resistance for many human bacterial pathogens. Advances in
      nanotechnology have opened new horizons in nanomedicine, allowing the synthesis
      of nanoparticles that can be assembled into complex architectures. Novel studies
      and technologies are devoted to understanding the mechanisms of disease for the
      design of new drugs, but unfortunately infectious diseases continue to be a major
      health burden worldwide. Since ancient times, silver was known for its anti
      bacterial effects and for centuries it has been used for prevention and control
      of disparate infections. Currently nanotechnology and nanomaterials are fully
      integrated in common applications and objects that we use every day. In addition,
      the silver nanoparticles are attracting much interest because of their potent
      antibacterial activity. Many studies have also shown an important activity of
      silver nanoparticles against bacterial biofilms. This review aims to summarize
      the emerging efforts to address current challenges and solutions in the treatment
      of infectious diseases, particularly the use of nanosilver antimicrobials. 

PMID- 25993418
TI  - Effect of extrusion cooking on bioactive compounds in encapsulated red cactus
      pear powder.
AB  - Red cactus pear has significant antioxidant activity and potential as a colorant
      in food, due to the presence of betalains. However, the betalains are highly
      thermolabile, and their application in thermal process, as extrusion cooking,
      should be evaluated. The aim of this study was to evaluate the effect of
      extrusion conditions on the chemical components of red cactus pear encapsulated
      powder. Cornstarch and encapsulated powder (2.5% w/w) were mixed and processed by
      extrusion at different barrel temperatures (80, 100, 120, 140  degrees C) and
      screw speeds (225, 275, 325 rpm) using a twin-screw extruder. Mean residence time
      (trm), color (L*, a*, b*), antioxidant activity, total polyphenol, betacyanin,
      and betaxanthin contents were determined on extrudates, and pigment degradation
      reaction rate constants (k) and activation energies (Ea) were calculated.
      Increases in barrel temperature and screw speed decreased the trm, and this was
      associated with better retentions of antioxidant activity, total polyphenol,
      betalain contents. The betacyanins k values ranged the -0.0188 to -0.0206/s and
      for betaxanthins ranged of -0.0122 to -0.0167/s, while Ea values were 1.5888 to
      6.1815 kJ/mol, respectively. The bioactive compounds retention suggests that
      encapsulated powder can be used as pigments and to provide antioxidant properties
      to extruded products. 

PMID- 25993419
TI  - Comparative Study on the Efficiency of the Photodynamic Inactivation of Candida
      albicans Using CdTe Quantum Dots, Zn(II) Porphyrin and Their Conjugates as
      Photosensitizers.
AB  - The application of fluorescent II-VI semiconductor quantum dots (QDs) as active
      photosensitizers in photodymanic inactivation (PDI) is still being evaluated. In
      the present study, we prepared 3 nm size CdTe QDs coated with mercaptosuccinic
      acid and conjugated them electrostatically with Zn(II) meso-tetrakis (N-ethyl-2
      pyridinium-2-yl) porphyrin (ZnTE-2-PyP or ZnP), thus producing QDs-ZnP
      conjugates. We evaluated the capability of the systems, bare QDs and conjugates,
      to produce reactive oxygen species (ROS) and applied them in photodynamic
      inactivation in cultures of Candida albicans by irradiating the QDs and testing
      the hypothesis of a possible combined contribution of the PDI action. Tests of in
      vitro cytotoxicity and phototoxicity in fibroblasts were also performed in the
      presence and absence of light irradiation. The overall results showed an
      efficient ROS production for all tested systems and a low cytotoxicity (cell
      viability >90%) in the absence of radiation. Fibroblasts incubated with the QDs
      ZnP and subjected to irradiation showed a higher cytotoxicity (cell viability
      <90%) depending on QD concentration compared to the bare groups. The PDI effects
      of bare CdTe QD on Candida albicans demonstrated a lower reduction of the cell
      viability (~1 log10) compared to bare ZnP which showed a high microbicidal
      activity (~3 log10) when photoactivated. The QD-ZnP conjugates also showed
      reduced photodynamic activity against C. albicans compared to bare ZnP and we
      suggest that the conjugation with QDs prevents the transmembrane cellular uptake
      of the ZnP molecules, reducing their photoactivity. 

PMID- 25993420
TI  - Influence of fruit maturity at harvest on the intensity of smoke taint in wine.
AB  - Bushfire smoke can affect the composition and sensory properties of grapes and
      wines, in some cases leading to wines which exhibit undesirable "smoky", "ashy"
      and "medicinal" characters. This study investigated the extent to which fruit
      maturity (i.e., ripeness) influences the perception of smoke taint in wine. Two
      white grape varieties (Chardonnay and Sauvignon Blanc) and two red grape
      varieties (Merlot and Shiraz) were exposed to smoke under experimental
      conditions, at approximately seven days post-veraison. Fruit was then harvested
      at two levels of maturity: Harvest A, when total soluble solids were 16-20 
      degrees Brix, i.e., the berry ripeness typically required for production of
      sparkling or light-bodied wines; and Harvest B, when total soluble solids were 22
      25  degrees Brix, i.e., the berry ripeness typically required for production of
      full-bodied wines. The intensity of smoke taint in resulting wines was found to
      be influenced by fruit maturity, but differed between grape varieties. Smoke
      related sensory attributes were apparent in Sauvignon Blanc wine made from early
      harvested fruit and in Chardonnay wine made from late-harvested fruit, only;
      whereas Merlot and Shiraz wines exhibited smoke taint irrespective of fruit
      maturity. Smoke-derived volatile phenols, and various alcohols, esters and acids,
      were also quantified to determine the impact of smoke exposure and fruit maturity
      respectively, on wine composition. 

PMID- 25993421
TI  - Absorption and Metabolism Characteristics of Triptolide as Determined by a
      Sensitive and Reliable LC-MS/MS Method.
AB  - In this research, a sensitive and reliable LC-MS/MS method was developed and
      applied to determine the concentration of triptolide in rat plasma, microsomes,
      and cell incubation media. The absolute oral bioavailability of triptolide is
      63.9% at a dose of 1 mg.kg-1. In vitro, the bidirectional transport of triptolide
      across Caco-2 cells was studied. A markedly higher transport of triptolide across
      Caco-2 cells was observed in the basolateral-to-apical direction and was
      abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated
      that P-gp might be involved in the absorption of triptolide in intestinal. The
      metabolic stability was also investigated using human liver microsome incubation
      systems in vitro. In HLMs, incubations with an initial triptolide concentration
      of 1 MUM resulted in an 82.4% loss of substrate over 60 min, and the t1/2 was 38
      min, which indicated that triptolide was easily metabolized in human liver
      microsomes. In conclusion, the absolute oral bioavailability of triptolide in
      plasma, transport across Caco-2 cell monolayers, and metabolic stability in human
      liver microsomes were systematically investigated by using a sensitive and
      reliable LC-MS/MS method. 

PMID- 25993422
TI  - Structural characteristics and non-linear optical behaviour of a 2
      hydroxynicotinate-containing zinc-based metal-organic framework.
AB  - Materials with non-linear optical (NLO) properties play an important role in the
      construction of electronic devices for optical communications, optical data
      processing and data storage. With this aim in mind, a Zn(II)-based metal-organic
      framework {[Zn2(nica)2(bpy)1.5(H2O)]*0.5(bpy)*3H2O}n (1), was synthesized using
      4,4'-bipyridine (bpy) and a potentially bidentate ligand, 2-hydroxynicotinic acid
      (H2nica) with a salicylate binding moiety. A single-crystal X-ray diffraction
      analysis revealed that compound 1 crystallized in the orthorhombic space group
      Fdd2 and was composed of a three dimensional porous framework. Since Fdd2
      belonged to a class of non-centrosymmetric space groups, we therefore
      investigated the non-linear optical behaviour of compound 1. Photoluminescence
      studies revealed that compound 1 exhibited a blue light emission with a maxima at
      457 nm. 

PMID- 25993423
TI  - Distinguishing Loss of Structure from Subunit Dissociation for Protein Complexes
      with Variable Temperature Ion Mobility Mass Spectrometry.
AB  - The thermal stability and strength of interactions in proteins are commonly
      measured using isothermal calorimetry and differential scanning calorimetry
      providing a measurement that averages over structural transitions that occur as
      the proteins melt and dissociate. Here, we apply variable temperature ion
      mobility mass spectrometry (VT-IM-MS) to study the effect of temperature on the
      stability and structure of four multimeric protein complexes. VT-IM-MS is used
      here to investigate the change in the conformation of model proteins, namely,
      transthyretin (TTR), avidin, concanavalin A (conA), and human serum amyloid P
      component (SAP) at elevated temperatures prior, during, and after dissociation up
      to 550 K. As the temperature of the buffer gas is increased from 300 to 350 K, a
      small decrease in the collision cross sections ((DT)CCS(He)) of protein complexes
      from the values at room temperature is observed, and is associated with complex
      compaction occurring close to the reported solution T(m). At significantly higher
      temperatures, each protein complex undergoes an increase in (DT)CCS(He) and in
      the width of arrival time distributions (ATD), which is attributed to extensive
      protein unfolding, prior to ejection of a highly charged monomer species. This
      approach allows us to decouple the distinct gas phase melting temperature (T(m))
      from the temperature at which we see subunit dissociation. The thermally induced
      dissociation (TID) mechanism is observed to initially proceed via the so-called
      "typical" (CID) dissociation route. Interestingly, data collected at higher
      analysis temperature suggests that the TID process might be adapting more
      "atypical" dissociation route.

PMID- 25993429
TI  - Characterization of the exchange of PBDEs in a subtropical paddy field of China:
      A significant inputs of PBDEs via air-foliage exchange.
AB  - Rice and the distinctive cultivation practices employed in rice growth can
      significantly influence the environmental fate of polybrominated diphenyl ethers
      (PBDEs) in a paddy field. We studied variations in PBDE concentrations in
      multiple compartments of a paddy field in the suburban area of Guangzhou, South
      China, including air, soil, water, and rice tissues. The input/output fluxes of
      air-surface and air-foliage exchange, atmospheric deposition and water input
      during different rice growth stages were measured simultaneously. Air-foliage and
      air-water diffusion exchanges were the key processes controlling inputs and
      outputs of PBDEs in paddy fields, respectively, whereas atmospheric deposition
      dominated inputs of higher brominated PBDEs. The high input of PBDEs via air
      foliage exchange suggested that vegetation can significantly increase the air-to
      field transport of PBDEs in ecosystems. The annual input of PBDEs in all paddy
      fields in Guangdong Province was estimated to be 22.1 kg.

PMID- 25993430
TI  - LOV Histidine Kinase Modulates the General Stress Response System and Affects the
      virB Operon Expression in Brucella abortus.
AB  - Brucella is the causative agent of the zoonotic disease brucellosis, and its
      success as an intracellular pathogen relies on its ability to adapt to the harsh
      environmental conditions that it encounters inside the host. The Brucella genome
      encodes a sensor histidine kinase containing a LOV domain upstream from the
      kinase, LOVHK, which plays an important role in light-regulated Brucella
      virulence. In this report we study the intracellular signaling pathway initiated
      by the light sensor LOVHK using an integrated biochemical and genetic approach.
      From results of bacterial two-hybrid assays and phosphotransfer experiments we
      demonstrate that LOVHK functionally interacts with two response regulators: PhyR
      and LovR, constituting a functional two-component signal-transduction system.
      LOVHK contributes to the activation of the General Stress Response (GSR) system
      in Brucella via PhyR, while LovR is proposed to be a phosphate-sink for LOVHK,
      decreasing its phosphorylation state. We also show that in the absence of LOVHK
      the expression of the virB operon is down-regulated. In conclusion, our results
      suggest that LOVHK positively regulates the GSR system in vivo, and has an effect
      on the expression of the virB operon. The proposed regulatory network suggests a
      similar role for LOVHK in other microorganisms. 

PMID- 25993431
TI  - The combined effects of moss-dominated biocrusts and vegetation on erosion and
      soil moisture and implications for disturbance on the Loess Plateau, China.
AB  - Biological soil crusts (BSCs, or biocrusts) have important positive ecological
      functions such as erosion control and soil fertility improvement, and they may
      also have negative effects on soil moisture in some cases. Simultaneous
      discussions of the two-sided impacts of BSCs are key to the rational use of this
      resource. This study focused on the contribution of BSCs while combining with
      specific types of vegetation to erosion reduction and their effects on soil
      moisture, and it addressed the feasibility of removal or raking disturbance.
      Twelve plots measuring 4 m * 2 m and six treatments (two plots for each) were
      established on a 15 degrees  slope in a small watershed in the Loess Plateau
      using BSCs, bare land (as a control, BL), Stipa bungeana Trin. (STBU), Caragana
      korshinskii Kom. (CAKO), STBU planted with BSCs (STBU+BSCs) and CAKO planted with
      BSCs (CAKO+BSCs). The runoff, soil loss and soil moisture to a depth of 3 m were
      measured throughout the rainy season (from June to September) of 2010. The
      results showed that BSCs significantly reduced runoff by 37.3% and soil loss by
      81.0% and increased infiltration by 12.4% in comparison with BL. However, when
      combined with STBU or CAKO, BSCs only made negligible contributions to erosion
      control (a runoff reduction of 7.4% and 5.7% and a soil loss reduction of 0.7%
      and 0.3%). Generally, the soil moisture of the vegetation plots was lower in the
      upper layer than that of the BL plots, although when accompanied with a higher
      amount of infiltration, this soil moisture consumption phenomenon was much
      clearer when combining vegetation with BSCs. Because of the trivial contributions
      from BSCs to erosion control and the remaining exacerbated consumption of soil
      water, moderate disturbance by BSCs should be considered in plots with adequate
      vegetation cover to improve soil moisture levels without a significant erosion
      increase, which was implied to be necessary and feasible. 

PMID- 25993432
TI  - Construction of a catsper1 DNA vaccine and its antifertility effect on male mice.
AB  - Cation channel of sperm 1 (CATSPER1) is a unique sperm cation channel protein,
      and essential for sperm function and male fertility. CATSPER1 exclusively
      expresses in meiotic and postmeiotic spermatogenic cells, thus belongs to the
      spermatogenesis-specific antigen that escape central tolerance. We have
      previously demonstrated the immunocontraceptive potential of its transmembrane
      domains and pore region, and reported the antifertility effects of its B-cell
      epitopes on male mice. Aiming to develop DNA vaccine targeting CATSPER1 for male
      contraception, here the whole open reading frame of mouse Catsper1 was cloned
      into the plasmid pEGFP-N1 to obtain a DNA vaccine pEGFP-N1-Catsper1. The vaccine
      was confirmed to be transcribed and translated in mouse N2a cell in vitro and
      mouse muscle tissue in vivo. Intramuscular injection with the vaccine on male
      mice induced specific immune reaction and caused significant inhibition on sperm
      hyperactivated motility and progressive motility (P<0.001 for both), and
      consequently reduced male fertility. The fertility rate of experimental group was
      40.9%, which was significant lower (P=0.012) than control group (81.8%). No
      significant change in mating behavior, sperm production and histology of
      testis/epididymis was observed. Given that Catsper1 exhibits a high degree of
      homology among different species, Catsper1 DNA vaccine might be a good strategy
      for developing an immunocontraceptive vaccine for human and animal use. 

PMID- 25993433
TI  - Tunable dielectric properties of ferrite-dielectric based metamaterial.
AB  - A ferrite-dielectric metamaterial composed of dielectric and ferrite cuboids has
      been investigated by experiments and simulations. By interacting with the
      electromagnetic wave, the Mie resonance can take place in the dielectric cuboids
      and the ferromagnetic precession will appear in the ferrite cuboids. The magnetic
      field distributions show the electric Mie resonance of the dielectric cuboids can
      be influenced by the ferromagnetic precession of ferrite cuboids when a certain
      magnetic field is applied. The effective permittivity of the metamaterial can be
      tuned by modifying the applied magnetic field. A good agreement between
      experimental and simulated results is demonstrated, which confirms that these
      metamaterials can be used for tunable microwave devices. 

PMID- 25993435
TI  - The breadth and mnemonic consequences of the youth bias.
AB  - We have recently demonstrated the existence of the youth bias, referring to a
      tendency to favour adolescence and early adulthood over other lifetime periods
      when making inferences about the timing of important public events across the
      lifespan of a typical individual within one's culture. The youth bias integrates
      two discrete lines of research, that is, the literature on the privileged status
      of adolescence and early adulthood in human memory and cognition, and the
      literature on cognitive biases. Here we first examined whether the youth bias
      holds for specific categories of public events (i.e., deaths of public figures,
      United States presidential elections, and sporting events). We then investigated
      the possible role of the youth bias in structuring recall for public events, by
      probing, within subjects, for the relation between: (1) these expectations of the
      timing, in a typical person's life, of the most important exemplar from each
      public event category, and (2) the age at which the cited event occurred on a
      recall question asking participants to cite the most important exemplar, in their
      own lifetime, from each category. We found a youth bias for each category.
      Additionally, responses to the youth bias question were correlated with the age
      at which the recalled event occurred, but only where particularly salient
      historical events did not play a central role in driving recall (i.e., for
      sporting events). We conclude that the youth bias holds across different types of
      public events and provides a default structure for organizing recall of public
      events. 

PMID- 25993434
TI  - Fluorescence lifetime imaging of endogenous biomarker of oxidative stress.
AB  - Presence of reactive oxygen species (ROS) in excess of normal physiological level
      results in oxidative stress. This can lead to a range of pathological conditions
      including inflammation, diabetes mellitus, cancer, cardiovascular and
      neurodegenerative disease. Biomarkers of oxidative stress play an important role
      in understanding the pathogenesis and treatment of these diseases. A number of
      fluorescent biomarkers exist. However, a non-invasive and label-free
      identification technique would be advantageous for in vivo measurements. In this
      work we establish a spectroscopic method to identify oxidative stress in cells
      and tissues by fluorescence lifetime imaging (FLIM). We identified an
      autofluorescent, endogenous species with a characteristic fluorescent lifetime
      distribution as a probe for oxidative stress. To corroborate our hypothesis that
      these species are products of lipid oxidation by ROS, we correlate the
      spectroscopic signals arising from lipid droplets by combining FLIM with THG and
      CARS microscopy which are established techniques for selective lipid body
      imaging. Further, we performed spontaneous Raman spectral analysis at single
      points of the sample which provided molecular vibration information
      characteristics of lipid droplets. 

PMID- 25993436
TI  - Association of SNP Rs9943582 in APLNR with Left Ventricle Systolic Dysfunction in
      Patients with Coronary Artery Disease in a Chinese Han GeneID Population.
AB  - Heart failure affects 1-2% of the adult population worldwide and coronary artery
      disease (CAD) is the underlying etiology of heart failure in 70% of the patients.
      The pathway of apelin and its apelin receptor (APJ) was implicated in the
      pathogenesis of heart failure in animal models, but a similar role in humans is
      unknown. We studied a functional variant, rs9943582 (-154G/A), at the 5'
      untranslated region, that was associated with decreased expression of the APJ
      receptor gene (APLNR) in a population consisting of 1,751 CAD cases and 1,022
      controls. Variant rs9943582 was not associated with CAD, but among CAD patients,
      it showed significant association with left ventricular systolic dysfunction (431
      CAD patients with left ventricular systolic dysfunction (LV ejection fraction or
      LVEF< 40%) versus 1,046 CAD patients without LV systolic dysfunction (LVEF>50%)
      (P-adj = 6.71 * 10(-5), OR = 1.43, 95% CI, 1.20-1.70). Moreover, rs9943582 also
      showed significant association with quantitative echocardiographic parameters,
      including left ventricular end-diastolic diameter (effect size: increased 1.67 +/
      0.43 mm per risk allele A, P = 1.15 * 10(-4)), left atrial size (effect size:
      increased 2.12 +/- 0.61 mm per risk allele A, P = 9.56 * 10(-4)) and LVEF (effect
      size: decreased 2.59 +/- 0.32 percent per risk allele A, P = 7.50 * 10(-15)). Our
      findings demonstrate that allele A of rs9943582 was significantly associated with
      left ventricular systolic dysfunction, left ventricular end-diastolic diameter,
      the left atrial diameter and LVEF in the CAD population, which suggests an
      important role of the apelin/APJ system in the pathology of heart failure
      associated with ischemic heart disease.

PMID- 25993438
TI  - Structure of a liquid/liquid interface during solvent extraction combining X-ray
      and neutron reflectivity measurements.
AB  - We have resolved the molecular structure of a bulk oil/water interface that
      contains amphiphilic ligand molecules using a combination of X-ray and neutron
      reflectivity measurements for the first time. This new capability can greatly
      impact future work in the field of ion separation by phase transfer, i.e.
      liquid/liquid extraction. 

PMID- 25993437
TI  - Eye movements provide an index of veridical memory for temporal order.
AB  - The present research examined whether eye movements during retrieval capture the
      relation between an event and its temporal attributes. In two experiments (N=76),
      we found converging evidence that eye movements reflected the veridicality of
      memory for temporal order seconds before overt memory judgments, suggesting that
      these movements captured indirect access to temporal information. These eye
      movements did not entirely depend on the amount of contextual cueing available
      (Experiment 1) and reflected the unique ordinal position of an event in a
      sequence (Experiment 2). Based on our results, we conclude that eye movements
      reflected the absolute temporal order of past events. 

PMID- 25993439
TI  - Differential Proteome Analysis Identifies TGF-beta-Related Pro-Metastatic
      Proteins in a 4T1 Murine Breast Cancer Model.
AB  - Transforming growth factor-beta (TGF-beta) has a dual role in tumorigenesis,
      acting as either a tumor suppressor or as a pro-oncogenic factor in a context
      dependent manner. Although TGF-beta antagonists have been proposed as anti
      metastatic therapies for patients with advanced stage cancer, how TGF-beta
      mediates metastasis-promoting effects is poorly understood. Establishment of TGF
      beta-related protein expression signatures at the metastatic site could provide
      new mechanistic information and potentially allow identification of novel
      biomarkers for clinical intervention to discriminate TGF-beta oncogenic effects
      from tumor suppressive effects. In the present study, we found that systemic
      administration of the TGF-beta receptor kinase inhibitor, SB-431542,
      significantly inhibited lung metastasis from transplanted 4T1 mammary tumors in
      Balb/c mice. The differentially expressed proteins in the comparison of lung
      metastases from SB-431542 treated and control vehicle-treated groups were
      analyzed by a quantitative LTQ Orbitrap Velos system coupled with stable isotope
      dimethyl labeling. A total of 36,239 peptides from 6,694 proteins were
      identified, out of which 4,531 proteins were characterized as differentially
      expressed. A subset of upregulated proteins in the control group was validated by
      western blotting and immunohistochemistry. The eukaryotic initiation factor (eIF)
      family members constituted the most enriched protein pathway in vehicle-treated
      compared with SB-43512-treated lung metastases, suggesting that increased protein
      expression of specific eIF family members, especially eIF4A1 and eEF2, is related
      to the metastatic phenotype of advanced breast cancer and can be down-regulated
      by TGF-beta pathway inhibitors. Thus our proteomic approach identified eIF
      pathway proteins as novel potential mediators of TGF-beta tumor-promoting
      activity. 

PMID- 25993440
TI  - Warming and Ocean Acidification Effects on Phytoplankton--From Species Shifts to
      Size Shifts within Species in a Mesocosm Experiment.
AB  - While the isolated responses of marine phytoplankton to climate warming and to
      ocean acidification have been studied intensively, studies on the combined effect
      of both aspects of Global Change are still scarce. Therefore, we performed a
      mesocosm experiment with a factorial combination of temperature (9 and 15 
      degrees C) and pCO2 (means: 439 ppm and 1040 ppm) with a natural autumn plankton
      community from the western Baltic Sea. Temporal trajectories of total biomass and
      of the biomass of the most important higher taxa followed similar patterns in all
      treatments. When averaging over the entire time course, phytoplankton biomass
      decreased with warming and increased with CO2 under warm conditions. The
      contribution of the two dominant higher phytoplankton taxa (diatoms and
      cryptophytes) and of the 4 most important species (3 diatoms, 1 cryptophyte) did
      not respond to the experimental treatments. Taxonomic composition of
      phytoplankton showed only responses at the level of subdominant and rare species.
      Phytoplankton cell sizes increased with CO2 addition and decreased with warming.
      Both effects were stronger for larger species. Warming effects were stronger than
      CO2 effects and tended to counteract each other. Phytoplankton communities
      without calcifying species and exposed to short-term variation of CO2 seem to be
      rather resistant to ocean acidification.

PMID- 25993441
TI  - Synthesis and Insecticidal Activity of Spinosyns with C9-O-Benzyl Bioisosteres in
      Place of the 2',3',4'-Tri-O-methyl Rhamnose.
AB  - The spinosyns are fermentation-derived natural products active against a wide
      range of insect pests. They are structurally complex, consisting of two sugars
      (forosamine and rhamnose) coupled to a macrocyclic tetracycle. Removal of the
      rhamnose sugar results in a >100-fold reduction in insecticidal activity. C9-O
      benzyl analogues of spinosyn D were synthesized to determine if the 2',3',4'-tri
      O-methyl rhamnose moiety could be replaced with a simpler, synthetic bioisostere.
      Insecticidal activity was evaluated against larvae of Spodoptera exigua (beet
      armyworm) and Helicoverpa zea (corn earworm). Whereas most analogues were far
      less active than spinosyn D, a few of the C9-O-benzyl analogues, such as 4-CN, 4
      Cl, 2-isopropyl, and 3,5-diOMe, were within 3-15 times the activity of spinosyn D
      for larvae of S. exigua and H. zea. Thus, although not yet quite as effective,
      synthetic bioisosteres can substitute for the naturally occurring 2',3',4'-tri-O
      methyl rhamnose moiety. 

PMID- 25993442
TI  - A Unique Virulence Gene Occupies a Principal Position in Immune Evasion by the
      Malaria Parasite Plasmodium falciparum.
AB  - Mutually exclusive gene expression, whereby only one member of a multi-gene
      family is selected for activation, is used by the malaria parasite Plasmodium
      falciparum to escape the human immune system and perpetuate long-term, chronic
      infections. A family of genes called var encodes the chief antigenic and
      virulence determinant of P. falciparum malaria. var genes are transcribed in a
      mutually exclusive manner, with switching between active genes resulting in
      antigenic variation. While recent work has shed considerable light on the
      epigenetic basis for var gene activation and silencing, how switching is
      controlled remains a mystery. In particular, switching seems not to be random,
      but instead appears to be coordinated to result in timely activation of
      individual genes leading to sequential waves of antigenically distinct parasite
      populations. The molecular basis for this apparent coordination is unknown. Here
      we show that var2csa, an unusual and highly conserved var gene, occupies a unique
      position within the var gene switching hierarchy. Induction of switching through
      the destabilization of var specific chromatin using both genetic and chemical
      methods repeatedly led to the rapid and exclusive activation of var2csa.
      Additional experiments demonstrated that these represent "true" switching events
      and not simply de-silencing of the var2csa promoter, and that activation is
      limited to the unique locus on chromosome 12. Combined with translational
      repression of var2csa transcripts, frequent "default" switching to this locus and
      detection of var2csa untranslated transcripts in non-pregnant individuals, these
      data suggest that var2csa could play a central role in coordinating switching,
      fulfilling a prediction made by mathematical models derived from population
      switching patterns. These studies provide the first insights into the mechanisms
      by which var gene switching is coordinated as well as an example of how a
      pharmacological agent can disrupt antigenic variation in Plasmodium falciparum. 

PMID- 25993443
TI  - The neutrophil-recruiting chemokine GCP-2/CXCL6 is expressed in cystic fibrosis
      airways and retains its functional properties after binding to extracellular DNA.
AB  - Infections in cystic fibrosis (CF), often involving Pseudomonas aeruginosa,
      result from a dysregulated airway immunity where one hallmark is the accumulation
      of necrotic and apoptotic immune cells, in particular neutrophils. In addition,
      neutrophils actively release DNA, forming neutrophil extracellular traps (NETs)
      that contain antimicrobial proteins. Altogether, free DNA in complex with actin
      accumulates in the airway lumen, resulting in highly viscous sputum that provides
      an anionic matrix, binding cationic antimicrobial proteins. In this study,
      granulocyte chemotactic protein 2 (GCP-2)/CXCL6, a neutrophil-activating
      chemokine with bactericidal properties, was detected in the airway epithelium of
      CF patients and was also present in azurophilic and specific granules of
      neutrophils. Elastase of neutrophils, but not of P. aeruginosa, completely
      degraded CXCL6 (chemokine (C-X-C motif) ligand 6). In addition, CXCL6 colocalized
      with extracellular DNA in both CF sputa and in in vitro-formed NETs. In vitro,
      CXCL6 bound DNA with a KD of 2,500 nM. Interestingly, both the bactericidal and
      the receptor-activating properties of CXCL6 (against neutrophils) remained
      largely unaffected in the presence of DNA. However, the chemotactic properties of
      CXCL6 were reduced by the presence of DNA. Taken together, CXCL6 is expressed in
      CF, retaining its functional properties even after binding to the anionic
      scaffold that extracellular DNA provides in CF. 

PMID- 25993444
TI  - Strain- and host species-specific inflammasome activation, IL-1beta release, and
      cell death in macrophages infected with uropathogenic Escherichia coli.
AB  - Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary
      tract infections (UTIs). Little is known about interactions between UPEC and the
      inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073
      and UTI89 trigger inflammasome activation and lytic cell death in human
      macrophages. Several other UPEC strains, including two multidrug-resistant ST131
      isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell
      death only at a high multiplicity of infection, and CFT073-mediated inflammasome
      responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89
      mediated responses only partially depended on NLRP3 in human macrophages. In
      these cells, NLRP3 was required for interleukin-1beta (IL-1beta) maturation, but
      contributed only marginally to cell death. Similarly, caspase-1 inhibition did
      not block cell death in human macrophages. In keeping with such differences, the
      pore-forming toxin alpha-hemolysin mediated a substantial proportion of CFT073
      triggered IL-1beta secretion in mouse but not human macrophages. There was also a
      more substantial alpha-hemolysin-independent cell death response in human vs.
      mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome
      responses are completely NLRP3-dependent, and largely alpha-hemolysin-dependent.
      In contrast, UPEC activates an NLRP3-independent cell death pathway and an alpha
      hemolysin-independent IL-1beta secretion pathway in human macrophages. This has
      important implications for understanding UTI in humans. 

PMID- 25993445
TI  - Nuclear matrix protein SMAR1 control regulatory  T-cell fate during inflammatory
      bowel disease (IBD).
AB  - Regulatory T (Treg) cells are essential for self-tolerance and immune
      homeostasis. Transcription factor Foxp3, a positive regulator of Treg cell
      differentiation, has been studied to some extent. Signal transducer and activator
      of transcription factor 3 (STAT3) is known to negatively regulate Foxp3. It is
      not clear how STAT3 is regulated during Treg differentiation. We show that SMAR1,
      a known transcription factor and tumor suppressor, is directly involved in
      maintaining Treg cell fate decision. T-cell-specific conditional knockdown of
      SMAR1 exhibits increased susceptibility towards inflammatory disorders, such as
      colitis. The suppressive function of Treg cells is compromised in the absence of
      SMAR1 leading to increased T helper type 17 (Th17) differentiation and
      inflammation. Compared with wild-type, the SMAR1(-/-) Treg cells showed increased
      susceptibility of inflammatory bowel disease in Rag1(-/ -) mice, indicating the
      role of SMAR1 in compromising Treg cell differentiation resulting in severe
      colitis. We show that SMAR1 negatively regulate STAT3 expression favoring Foxp3
      expression and Treg cell differentiation. SMAR1 binds to the MAR element of STAT3
      promoter, present adjacent to interleukin-6 response elements. Thus Foxp3, a
      major driver of Treg cell differentiation, is regulated by SMAR1 via STAT3 and a
      fine-tune balance between Treg and Th17 phenotype is maintained.

PMID- 25993446
TI  - Biochemical, Kinetic, and Spectroscopic Characterization of Ruegeria pomeroyi
      DddW--A Mononuclear Iron-Dependent DMSP Lyase.
AB  - The osmolyte dimethylsulfoniopropionate (DMSP) is a key nutrient in marine
      environments and its catabolism by bacteria through enzymes known as DMSP lyases
      generates dimethylsulfide (DMS), a gas of importance in climate regulation, the
      sulfur cycle, and signaling to higher organisms. Despite the environmental
      significance of DMSP lyases, little is known about how they function at the
      mechanistic level. In this study we biochemically characterize DddW, a DMSP lyase
      from the model roseobacter Ruegeria pomeroyi DSS-3. DddW is a 16.9 kDa enzyme
      that contains a C-terminal cupin domain and liberates acrylate, a proton, and DMS
      from the DMSP substrate. Our studies show that as-purified DddW is a
      metalloenzyme, like the DddQ and DddP DMSP lyases, but contains an iron cofactor.
      The metal cofactor is essential for DddW DMSP lyase activity since addition of
      the metal chelator EDTA abolishes its enzymatic activity, as do substitution
      mutations of key metal-binding residues in the cupin motif (His81, His83, Glu87,
      and His121). Measurements of metal binding affinity and catalytic activity
      indicate that Fe(II) is most likely the preferred catalytic metal ion with a
      nanomolar binding affinity. Stoichiometry studies suggest DddW requires one
      Fe(II) per monomer. Electronic absorption and electron paramagnetic resonance
      (EPR) studies show an interaction between NO and Fe(II)-DddW, with NO binding to
      the EPR silent Fe(II) site giving rise to an EPR active species (g = 4.29, 3.95,
      2.00). The change in the rhombicity of the EPR signal is observed in the presence
      of DMSP, indicating that substrate binds to the iron site without displacing
      bound NO. This work provides insight into the mechanism of DMSP cleavage
      catalyzed by DddW. 

PMID- 25993447
TI  - Paw-dragging: a novel, sensitive analysis of the mouse cylinder test.
AB  - The cylinder test is routinely used to predict focal ischemic damage to the
      forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by
      rearing and touching the walls of the cylinder with their forelimb paws for
      postural support. Following ischemic injury to the forelimb sensorimotor cortex,
      rats rely more heavily on their unaffected forelimb paw for postural support
      resulting in fewer touches with their affected paw which is termed forelimb
      asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result
      in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry
      deficits are infrequently observed, mice do demonstrate a novel behaviour post
      stroke termed "paw-dragging". Paw-dragging is the tendency for a mouse to drag
      its affected paw along the cylinder wall rather than directly push off from the
      wall when dismounting from a rear to a four-legged stance. We have previously
      demonstrated that paw-dragging behaviour is highly sensitive to small cortical
      ischemic injuries to the forelimb motor cortex. Here we provide a detailed
      protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate
      how to quantify paw-dragging behaviour. The cylinder test is a simple and
      inexpensive test to administer and does not require pre-training or food
      deprivation strategies. In using paw-dragging analysis with the cylinder test, it
      fills a niche for predicting cortical ischemic injuries such as photothrombosis
      and Endothelin-1 (ET-1)-induced ischemia--two models that are ever-increasing in
      popularity and produce smaller focal injuries than middle cerebral artery
      occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will
      allow studies of functional recovery after cortical injury using a wide cohort of
      transgenic mouse strains where previous forelimb asymmetry analysis has failed to
      detect consistent deficits.

PMID- 25993449
TI  - Helping Meet Surgical Needs in Under-resourced Settings: The Role of Task
      Shifting.

PMID- 25993450
TI  - Transforming practice--learning from our peers.

PMID- 25993451
TI  - New graduate nurses, new graduate nurse transition programs, and clinical
      leadership skill: a systematic review.
AB  - This systematic review evaluated the relationship between new graduate nurses and
      clinical leadership skill, and between new graduate nurse transition programs and
      clinical leadership skill. New graduate nurse transition programs have been cited
      as one strategy to improve clinical leadership skill, but to our knowledge, no
      one has synthesized the evidence on new graduate nurse transition programs and
      clinical leadership skill. Results of this review showed that new graduate nurse
      transition programs that were at least 24 weeks in length had a positive impact
      on clinical leadership skill. New graduate nurse transition programs using the
      University HealthSystem Consortium/American Association of Colleges of Nursing
      Nurse Residency curriculum had the greatest impact, followed by curriculum
      developed by the Versant New Graduate RN Residency, an important finding for
      nursing professional development specialists. 

PMID- 25993452
TI  - Exploring problems encountered among experienced nurses using critical reflective
      inquiry: implications for nursing professional development.
AB  - This study explored problems encountered by nurses using critical reflective
      inquiry to examine clinical situations and the impact of group discussion on the
      reflective process. Secondary qualitative analysis of 19 reflective situations,
      rom a reflection continuing education program, revealed that nurses had
      problematic pauses in reflection and were stuck in cyclical self-questioning.
      Peer group discussion prompted deeper reflection. Experienced nurses may need
      assistance to enhance the comprehensiveness, depth, and scope of reflection on
      practice situations. 

PMID- 25993453
TI  - The Dedicated Education Unit Experience: What's in It for Professional
      Development Nurses?
AB  - Dedicated Education Units (DEU) may be one strategy for staff development
      educators to address new graduate nurse transition to practice and turnover
      within the first year of practice. This qualitative study explored the
      experiences of students and staff nurses from the inaugural DEU at Research
      College of Nursing and Research Medical Center. The themes identified suggest
      that students who were educated in the DEU model may be better prepared to
      practice in the "real world" of nursing than their peers who were not. 

PMID- 25993454
TI  - The effects of a prelicensure extern program and nurse residency program on new
      graduate outcomes and retention.
AB  - Organizations are looking to new graduate nurses to fill expected staffing
      shortages over the next decade. Creative and effective onboarding programs will
      determine the success or failure of these graduates as they transition from
      student to professional nurse. This longitudinal quantitative study with repeated
      measures used the Casey-Fink Graduate Nurse Experience Survey to investigate the
      effects of offering a prelicensure extern program and postlicensure residency
      program on new graduate nurses and organizational outcomes versus a residency
      program alone. Compared with the nurse residency program alone, the combination
      of extern program and nurse residency program improved neither the transition
      factors most important to new nurse graduates during their first year of practice
      nor a measure important to organizations, retention rates. The additional cost of
      providing an extern program should be closely evaluated when making financially
      responsible decisions. 

PMID- 25993455
TI  - Factors related to nurse comfort when caring for families experiencing perinatal
      loss: evidence for bereavement program enhancement.
AB  - As nurses provide holistic support, their own comfort in caring for parents and
      families experiencing perinatal loss must be considered. Study results showed
      that, although education is essential, experience independently predicted comfort
      in delivering perinatal bereavement care. Evidence from this study promotes the
      discussion of how nurse educators can structure professional development programs
      to best transfer the experience and confidence of perinatal nurses who are
      already comfortable with bereavement care to nurses who are not. 

PMID- 25993456
TI  - How mental health nurses improve their critical thinking through problem-based
      learning.
AB  - Critical thinking has been regarded as one of the most important elements for
      nurses to improve quality of patient care. The aim of this study was to use
      problem-based learning (PBL) as a method in a continuing education program to
      evaluate nurses' critical thinking skills. A quasiexperimental study design was
      carried out. The "Critical Thinking Disposition Inventory" in Chinese was used
      for data collection. The results indicated significant improvement after PBL
      continuous education, notably in the dimensions of systematic analysis and
      curiosity. Content analysis extracted four themes: (a) changes in linear thinking
      required, (b) logical and systematic thinking required performance improved, (3)
      integration of prior knowledge and clinical application, and (4) brainstorming
      learning strategy. The study supports PBL as a continuing education strategy for
      mental health nurses, and that systematic analysis and curiosity effectively
      facilitate the development of critical thinking. 

PMID- 25993457
TI  - Are your classes more like a maze or a labyrinth?

PMID- 25993458
TI  - Results From the National Council of State Boards of Nursing's Transition to
      Practice Study, Part 1.

PMID- 25993459
TI  - Analyzing performance discrepancies--part 2.

PMID- 25993460
TI  - Using Simulation to Develop Leadership, Communication, Collaboration, Advising,
      and Mentoring Skills: Opportunities for the NPD Specialist.

PMID- 25993462
TI  - Nursing innovations and outcomes.

PMID- 25993463
TI  - Utilization of electronic modified early warning score to engage rapid response
      team early in clinical deterioration.
AB  - After implementation of electronic modified early warning score to engage the
      rapid response team as a clinical decision support tool, we assessed the
      knowledge level about and usage of the tool by core staff. We identified a
      knowledge deficit, planned and implemented an educational intervention, and
      measured the outcome of the intervention. The outcome measurement indicated
      improved use of the clinical decision support tool by core staff and improved
      patient rescue strategies. 

PMID- 25993465
TI  - Phosphorylation of Nonmuscle myosin II-A regulatory light chain resists Sendai
      virus fusion with host cells.
AB  - Enveloped viruses enter host cells through membrane fusion and the cells in turn
      alter their shape to accommodate components of the virus. However, the role of
      nonmuscle myosin II of the actomyosin complex of host cells in membrane fusion is
      yet to be understood. Herein, we show that both (-) blebbistatin, a specific
      inhibitor of nonmuscle myosin II (NMII) and small interfering RNA markedly
      augment fusion of Sendai virus (SeV), with chinese hamster ovary cells and human
      hepatocarcinoma cells. Inhibition of RLC phosphorylation using inhibitors against
      ROCK, but not PKC and MRCK, or overexpression of phospho-dead mutant of RLC
      enhances membrane fusion. SeV infection increases cellular stiffness and myosin
      light chain phosphorylation at two hour post infection. Taken together, the
      present investigation strongly indicates that Rho-ROCK-NMII contractility
      signaling pathway may provide a physical barrier to host cells against viral
      fusion. 

PMID- 25993466
TI  - Evaluation of Changes in Morphology and Function of Human Induced Pluripotent
      Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber
      Cardiac Patch.
AB  - INTRODUCTION: Dilated cardiomyopathy is a major cause of progressive heart
      failure. Utilization of stem cell therapy offers a potential means of
      regenerating viable cardiac tissue. However, a major obstacle to stem cell
      therapy is the delivery and survival of implanted stem cells in the ischemic
      heart. To address this issue, we have developed a biomimetic aligned nanofibrous
      cardiac patch and characterized the alignment and function of human inducible
      pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac
      patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on
      standard flat cell culture plates. METHODS: hiPSC-CMs were cultured on; 1) a
      highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns
      thick) and 2) on a standard flat culture plate. Scanning electron microscopy
      (SEM) was used to determine alignment of PLGA nanofibers and orientation of the
      cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was
      performed by confocal imaging in both the groups. Calcium cycling and patch-clamp
      technique were performed to measure calcium transients and electrical coupling
      properties of cardiomyocytes. RESULTS: SEM demonstrated >90% alignment of the
      nanofibers in the patch which is similar to the extracellular matrix of
      decellularized rat myocardium. Confocal imaging of the cardiomyocytes
      demonstrated symmetrical alignment in the same direction on the aligned nanofiber
      patch in sharp contrast to the random appearance of cardiomyocytes cultured on a
      tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches
      showed more efficient calcium cycling compared with cells cultured on standard
      flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that
      these cardiomyocytes expressed alpha-actinin, troponin-T and connexin-43 in
      vitro. CONCLUSIONS: Overall, our results demonstrated changes in morphology and
      function of human induced pluripotent derived cardiomyocytes cultured in an
      anisotropic environment created by an aligned nanofiber patch. In this
      environment, these cells better approximate normal cardiac tissue compared with
      cells cultured on flat surface and can serve as the basis for bioengineering of
      an implantable cardiac patch.

PMID- 25993467
TI  - Regenerative and immunogenic characteristics of cultured nucleus pulposus cells
      from human cervical intervertebral discs.
AB  - Cell-based regenerative approaches have been suggested as primary or adjuvant
      procedures for the treatment of degenerated intervertebral disc (IVD) diseases.
      Our aim was to evaluate the regenerative and immunogenic properties of mildly and
      severely degenerated cervical nucleus pulposus (NP) cells with regard to cell
      isolation, proliferation and differentiation, as well as to cell surface markers
      and co-cultures with autologous or allogeneic peripheral blood mononuclear cells
      (PBMC) including changes in their immunogenic properties after 3-dimensional (3D)
      culture. Tissue from the NP compartment of 10 patients with mild or severe grades
      of IVD degeneration was collected. Cells were isolated, expanded with and without
      basic fibroblast growth factor and cultured in 3D fibrin/poly (lactic-co
      glycolic) acid transplants for 21 days. Real-time reverse-transcription
      polymerase chain reaction (RT-PCR) showed the expression of characteristic NP
      markers ACAN, COL1A1 and COL2A1 in 2D- and 3D-culture with degeneration- and
      culture-dependent differences. In a 5,6-carboxyfluorescein diacetate N
      succinimidyl ester-based proliferation assay, NP cells in monolayer, regardless
      of their grade of degeneration, did not provoke a significant proliferation
      response in T cells, natural killer (NK) cells or B cells, not only with donor
      PBMC, but also with allogeneic PBMC. In conjunction with low inflammatory
      cytokine expression, analyzed by Cytometric Bead Array and fluorescence-activated
      cell sorting (FACS), a low immunogenicity can be assumed, facilitating possible
      therapeutic approaches. In 3D-culture, however, we found elevated immune cell
      proliferation levels, and there was a general trend to higher responses for NP
      cells from severely degenerated IVD tissue. This emphasizes the importance of
      considering the specific immunological alterations when including biomaterials in
      a therapeutic concept. The overall expression of Fas receptor, found on cultured
      NP cells, could have disadvantageous implications on their potential therapeutic
      applications because they could be the targets of cytotoxic T-cell activity
      acting by Fas ligand-induced apoptosis. 

PMID- 25993468
TI  - Seroprevalence of Toxoplasma gondii in wild boars, red deer and roe deer in
      Poland.
AB  - Little is known about the prevalence of Toxoplasma gondii in wild life,
      particularly game animals in Poland. Meat juice collected during the 2009/2010
      and 2010/2011 hunting seasons from 552 red deer (Cervus elaphus), 367 wild boars
      (Sus scrofa) and 92 roe deer (Capreolus capreolus) was tested for T. gondii
      antibodies using the multi-species ID Screen Toxoplasmosis Indirect kit (IDvet,
      Montpellier, France). Antibodies to T. gondii were detected in 24.1% of red deer
      (95% CI: 20.7%, 27.8%), 37.6% of wild boar (95% CI: 32.8%, 42.7%) and 30.4% of
      roe deer (95% CI: 22.0%, 40.5%). To the authors' best knowledge, this is the
      first epidemiological report of T. gondii prevalence in red deer, roe deer and
      wild boars in Poland. T. gondii is present in wildlife animal tissues and
      consumption of the game may be a potential source of infection for humans. 

PMID- 25993469
TI  - A novel artificial bee colony based clustering algorithm for categorical data.
AB  - Data with categorical attributes are ubiquitous in the real world. However,
      existing partitional clustering algorithms for categorical data are prone to fall
      into local optima. To address this issue, in this paper we propose a novel
      clustering algorithm, ABC-K-Modes (Artificial Bee Colony clustering based on K
      Modes), based on the traditional k-modes clustering algorithm and the artificial
      bee colony approach. In our approach, we first introduce a one-step k-modes
      procedure, and then integrate this procedure with the artificial bee colony
      approach to deal with categorical data. In the search process performed by scout
      bees, we adopt the multi-source search inspired by the idea of batch processing
      to accelerate the convergence of ABC-K-Modes. The performance of ABC-K-Modes is
      evaluated by a series of experiments in comparison with that of the other popular
      algorithms for categorical data. 

PMID- 25993472
TI  - Synchronization of two homodromy rotors installed on a double vibro-body in a
      coupling vibration system.
AB  - A new mechanism is proposed to implement synchronization of the two unbalanced
      rotors in a vibration system, which consists of a double vibro-body, two
      induction motors and spring foundations. The coupling relationship between the
      vibro-bodies is ascertained with the Laplace transformation method for the
      dynamics equation of the system obtained with the Lagrange's equation. An
      analytical approach, the average method of modified small parameters, is employed
      to study the synchronization characteristics between the two unbalanced rotors,
      which is converted into that of existence and the stability of zero solutions for
      the non-dimensional differential equations of the angular velocity disturbance
      parameters. By assuming the disturbance parameters that infinitely approach to
      zero, the synchronization condition for the two rotors is obtained. It indicated
      that the absolute value of the residual torque between the two motors should be
      equal to or less than the maximum of their coupling torques. Meanwhile, the
      stability criterion of synchronization is derived with the Routh-Hurwitz method,
      and the region of the stable phase difference is confirmed. At last, computer
      simulations are preformed to verify the correctness of the approximate solution
      of the theoretical computation for the stable phase difference between the two
      unbalanced rotors, and the results of theoretical computation is in accordance
      with that of computer simulations. To sum up, only the parameters of the
      vibration system satisfy the synchronization condition and the stability
      criterion of the synchronization, the two unbalanced rotors can implement the
      synchronization operation. 

PMID- 25993470
TI  - Sirtuin3 Dysfunction Is the Key Determinant of Skeletal Muscle Insulin Resistance
      by Angiotensin II.
AB  - BACKGROUND: Angiotensin II promotes insulin resistance. The mechanism underlying
      this abnormality, however, is still poorly defined. In a different setting,
      skeletal muscle metabolism and insulin signaling are regulated by Sirtuin3.
      OBJECTIVE: Here, we investigate whether angiotensin II-induced insulin resistance
      in skeletal muscle is associated with Sirtuin3 dysregulation and whether
      pharmacological manipulation of Sirtuin3 confers protection. STUDY DESIGN:
      Parental and GLUT4-myc L6 rat skeletal muscle cells exposed to angiotensin II are
      used as in vitro models of insulin resistance. GLUT4 translocation, glucose
      uptake, intracellular molecular signals such as mitochondrial reactive oxygen
      species, Sirtuin3 protein expression and activity, along with its downstream
      targets and upstream regulators, are analyzed both in the absence and presence of
      acetyl-L-carnitine. The role of Sirtuin3 in GLUT4 translocation and intracellular
      molecular signaling is also studied in Sirtuin3-silenced as well as over
      expressing cells. RESULTS: Angiotensin II promotes insulin resistance in skeletal
      muscle cells via mitochondrial oxidative stress, resulting in a two-fold increase
      in superoxide generation. In this context, reactive oxygen species open the
      mitochondrial permeability transition pore and significantly lower Sirtuin3
      levels and activity impairing the cell antioxidant defense. Angiotensin II
      induced Sirtuin3 dysfunction leads to the impairment of AMP-activated protein
      kinase/nicotinamide phosphoribosyltransferase signaling. Acetyl-L-carnitine, by
      lowering angiotensin II-induced mitochondrial superoxide formation, prevents
      Sirtuin3 dysfunction. This phenomenon implies the restoration of manganese
      superoxide dismutase antioxidant activity and AMP-activated protein kinase
      activation. Acetyl-L-carnitine protection is abrogated by specific Sirtuin3
      siRNA. CONCLUSIONS: Our data demonstrate that angiotensin II-induced insulin
      resistance fosters mitochondrial superoxide generation, in turn leading to
      Sirtuin3 dysfunction. The present results also highlight Sirtuin3 as a
      therapeutic target for the insulin-sensitizing effects of acetyl-L-carnitine.

PMID- 25993471
TI  - Long-Term Over-Expression of Neuropeptide Y in Hypothalamic Paraventricular
      Nucleus Contributes to Adipose Tissue Insulin Resistance Partly via the Y5
      Receptor.
AB  - Intracerebroventricular injection and overexpression of Neuropeptide Y (NPY) in
      the paraventricular nucleus (PVN) has been shown to induce obesity and glucose
      metabolism disorder in rodents; however, the underlying mechanisms are still
      unclear. The aim of this study was to investigate the mechanism contributing to
      glucose metabolic disturbance induced by NPY. Recombinant lentiviral NPY vectors
      were injected into the PVN of rats fed a high fat (HFD) or low-fat diet. 8 weeks
      later, in vivo intravenous glucose tolerance tests and euglycemic
      hyperinsulinemic clamp revealed that insulin resistance of adipose tissue were
      induced by NPY overexpression with or without HFD. NPY increased food intake, but
      did not change blood glucose, glycated hemoglobin A1c (HbA1c) or lipid levels.
      However, NPY decreased the expression of pGSK3beta, PI3K p85 and pAKTSer473 in
      adipose tissue of rats. In vitro, 3T3-L1 adipocytes were treated with NPY, NPY Y1
      and Y5 receptor antagonists. Glucose consumption and 2-deoxy-D-[3H] glucose
      uptake were partly inhibited by NPY, while a decrease in PI3K-AKT pathway
      signaling and a decreased expression of pGSK3alpha and pGSK3beta were observed.
      Nevertheless, a Y5 receptor antagonist (L-152,804) reversed the effects of NPY on
      glucose uptake and consumption. These data suggest that long-term over-expression
      of NPY in PVN contributes to the establishment of adipose tissue insulin
      resistance, at least partly via the Y5 Receptor. 

PMID- 25993473
TI  - Distribution of Residence Time of Water around DNA Base Pairs: Governing Factors
      and the Origin of Heterogeneity.
AB  - Water dynamics in the solvation shell around biomolecules plays a vital role in
      their stability, function, and recognition processes. Although extensively
      studied through various experimental and computational methods, dynamical time
      scales of water near DNA is highly debated. The residence time of water is one
      such dynamical quantity that has been probed rarely around DNA using
      computational methods. Moreover, the effect of local DNA sequence variation in
      water residence time has also not been addressed. Using 20 DNA systems with
      different sequences, we capture here the mean residence time (MRT) of water
      molecules around 360 different sites in the major and minor grooves of DNA. Thus,
      we show that a distribution of time scales exists even for a regular structure of
      DNA, reflecting the effect of chemistry, topography, and other factors governing
      dynamics of water. We used the stable state picture (SSP) formalism to calculate
      MRT that avoids the effect of transient recrossing. Results obtained from
      simulations agree well with experiments done on a few specific systems at a
      similar temperature. Most importantly, we find that although the groove width and
      depth influence water time scale, MRT of water is always longer in the middle of
      the DNA, in agreement with NMR experiments. We propose a simple kinetic model of
      water escape from DNA where water molecules move along the DNA and perpendicular
      to it in both the first and second solvation shell before it escapes to bulk. We
      show that this simple kinetic model captures both the time scale and the position
      dependence of MRT of water around DNA. This study thus portrays the origin and a
      measure of heterogeneity in water dynamics around DNA and provides a fresh
      perspective in the ongoing debate on water dynamical time scales around DNA.

PMID- 25993474
TI  - Diffusion and topological neighbours in flocks of starlings: relating a model to
      empirical data.
AB  - Moving in a group while avoiding collisions with group members causes internal
      dynamics in the group. Although these dynamics have recently been measured
      quantitatively in starling flocks (Sturnus vulgaris), it is unknown what causes
      them. Computational models have shown that collective motion in groups is likely
      due to attraction, avoidance and, possibly, alignment among group members.
      Empirical studies show that starlings adjust their movement to a fixed number of
      closest neighbours or topological range, namely 6 or 7 and assume that each of
      the three activities is done with the same number of neighbours (topological
      range). Here, we start from the hypothesis that escape behavior is more effective
      at preventing collisions in a flock when avoiding the single closest neighbor
      than compromising by avoiding 6 or 7 of them. For alignment and attraction, we
      keep to the empirical topological range. We investigate how avoiding one or
      several neighbours affects the internal dynamics of flocks of starlings in our
      computational model StarDisplay. By comparing to empirical data, we confirm that
      internal dynamics resemble empirical data more closely if flock members avoid
      merely their single, closest neighbor. Our model shows that considering a
      different number of interaction partners per activity represents a useful
      perspective and that changing a single parameter, namely the number of
      interaction partners that are avoided, has several effects through
      selforganisation. 

PMID- 25993475
TI  - A 3-component mixture of Rayleigh distributions: properties and estimation in
      Bayesian framework.
AB  - To study lifetimes of certain engineering processes, a lifetime model which can
      accommodate the nature of such processes is desired. The mixture models of
      underlying lifetime distributions are intuitively more appropriate and appealing
      to model the heterogeneous nature of process as compared to simple models. This
      paper is about studying a 3-component mixture of the Rayleigh distributionsin
      Bayesian perspective. The censored sampling environment is considered due to its
      popularity in reliability theory and survival analysis. The expressions for the
      Bayes estimators and their posterior risks are derived under different scenarios.
      In case the case that no or little prior information is available, elicitation of
      hyperparameters is given. To examine, numerically, the performance of the Bayes
      estimators using non-informative and informative priors under different loss
      functions, we have simulated their statistical properties for different sample
      sizes and test termination times. In addition, to highlight the practical
      significance, an illustrative example based on a real-life engineering data is
      also given.

PMID- 25993476
TI  - Congestion transition in air traffic networks.
AB  - Air Transportation represents a very interesting example of a complex techno
      social system whose importance has considerably grown in time and whose
      management requires a careful understanding of the subtle interplay between
      technological infrastructure and human behavior. Despite the competition with
      other transportation systems, a growth of air traffic is still foreseen in Europe
      for the next years. The increase of traffic load could bring the current Air
      Traffic Network above its capacity limits so that safety standards and
      performances might not be guaranteed anymore. Lacking the possibility of a direct
      investigation of this scenario, we resort to computer simulations in order to
      quantify the disruptive potential of an increase in traffic load. To this end we
      model the Air Transportation system as a complex dynamical network of flights
      controlled by humans who have to solve potentially dangerous conflicts by
      redirecting aircraft trajectories. The model is driven and validated through
      historical data of flight schedules in a European national airspace. While
      correctly reproducing actual statistics of the Air Transportation system, e.g.,
      the distribution of delays, the model allows for theoretical predictions. Upon an
      increase of the traffic load injected in the system, the model predicts a
      transition from a phase in which all conflicts can be successfully resolved, to a
      phase in which many conflicts cannot be resolved anymore. We highlight how the
      current flight density of the Air Transportation system is well below the
      transition, provided that controllers make use of a special re-routing procedure.
      While the congestion transition displays a universal scaling behavior, its
      threshold depends on the conflict solving strategy adopted. Finally, the
      generality of the modeling scheme introduced makes it a flexible general tool to
      simulate and control Air Transportation systems in realistic and synthetic
      scenarios. 

PMID- 25993477
TI  - The up-scaling of ecosystem functions in a heterogeneous world.
AB  - Earth is in the midst of a biodiversity crisis that is impacting the functioning
      of ecosystems and the delivery of valued goods and services. However, the
      implications of large scale species losses are often inferred from small scale
      ecosystem functioning experiments with little knowledge of how the dominant
      drivers of functioning shift across scales. Here, by integrating observational
      and manipulative experimental field data, we reveal scale-dependent influences on
      primary productivity in shallow marine habitats, thus demonstrating the
      scalability of complex ecological relationships contributing to coastal marine
      ecosystem functioning. Positive effects of key consumers (burrowing urchins,
      Echinocardium cordatum) on seafloor net primary productivity (NPP) elucidated by
      short-term, single-site experiments persisted across multiple sites and years.
      Additional experimentation illustrated how these effects amplified over time,
      resulting in greater primary producer biomass (sediment chlorophyll a content) in
      the longer term, depending on climatic context and habitat factors affecting the
      strengths of mutually reinforcing feedbacks [corrected]. The remarkable coherence
      of results from small and large scales is evidence of real-world ecosystem
      function scalability and ecological self-organisation. This discovery provides
      greater insights into the range of responses to broad-scale anthropogenic
      stressors in naturally heterogeneous environmental settings.

PMID- 25993479
TI  - C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis.
AB  - C-peptide has intrinsic biological activity and may be renoprotective. We
      conducted a systematic review to determine whether C-peptide had a beneficial
      effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases
      were searched for human and animal studies in which C-peptide was administered
      and renal endpoints were subsequently measured. We identified 4 human trials
      involving 74 patients as well as 18 animal studies involving 35 separate
      experiments with a total of 641 animals. In humans, the renal effects of
      exogenously delivered C-peptide were only studied in type 1 diabetics with either
      normal renal function or incipient nephropathy. Pooled analysis showed no
      difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72) in patients
      receiving C-peptide compared to a control group, but two studies reported a
      reduction in glomerular hyperfiltration (p<0.05). Reduction in albuminuria was
      also reported in the C-peptide group (p<0.05). In diabetic rodent models, C
      peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001)
      reflecting a partial reduction in glomerular hyperfiltration. C-peptide also
      reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05), glomerular
      volume (p<0.00001), and mesangial matrix area (p<0.00001) in diabetic animals
      without affecting blood pressure or plasma glucose. Most studies were relatively
      short-term in duration, ranging from 1 hour to 3 months. Human studies of
      sufficient sample size and duration are needed to determine if the beneficial
      effects of C-peptide seen in animal models translate into improved long-term
      clinical outcomes for patients with chronic kidney disease. (PROSPERO
      CRD42014007472). 

PMID- 25993478
TI  - The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of
      Clostridium perfringens epsilon-Toxin.
AB  - Clostridium perfringens epsilon-toxin (ETX) is a potent pore-forming toxin
      responsible for a central nervous system (CNS) disease in ruminant animals with
      characteristics of blood-brain barrier (BBB) dysfunction and white matter injury.
      ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS),
      a human disease that begins with BBB breakdown and injury to myelin forming cells
      of the CNS. The receptor for ETX is unknown. Here we show that both binding of
      ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin
      and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are
      resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX
      binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL
      are ~100 times more sensitive to ETX than cells expressing similar levels of
      human MAL. Insertion of the FLAG sequence into the second extracellular loop of
      MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and
      with high affinity to intestinal epithelium, renal tubules, brain endothelial
      cells and myelin. We identify specific binding of ETX to these structures and
      additionally show binding to retinal microvasculature and the squamous epithelial
      cells of the sclera in wild-type mice. In contrast, there is a complete absence
      of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/-
      mice exhibit complete resistance to ETX at doses in excess of 1000 times the
      symptomatic dose for wild-type mice. We conclude that MAL is required for both
      ETX binding and cytotoxicity. 

PMID- 25993480
TI  - Alterations in adhesion molecules, pro-inflammatory cytokines and cell-derived
      microparticles contribute to intima-media thickness and symptoms in
      postmenopausal women.
AB  - Menopause, the cessation of menses, occurs with estrogens decline, low-grade
      inflammation, and impaired endothelial function, contributing to atherosclerotic
      risk. Intima-media thickness (IMT) is an early subclinical biomarker of
      atherosclerosis. Inflammation may have a role on symptoms: hot flashes, anxiety,
      and depressive mood, which also are related to endothelial dysfunction, increased
      IMT and cardiovascular risk. In this study we compared several inflammatory
      markers in early vs. late postmenopausal women and studied the association of IMT
      and symptoms with these markers in the full sample. In a cross-sectional design
      including 60 women (53.1 +/- 4.4 years old) at early and late postmenopause, we
      evaluated the expression of CD62L, ICAM-1, PSGL-1, CD11b, CD11c, and IL-8R on
      PBMC by flow cytometry. Serum soluble ICAM-1, sVCAM-1, sCD62E, sCD62P, CXCL8, IL
      1beta, IL-6, and TNF-alpha levels were quantified by ELISA. Plasma levels of
      microparticles (MPs) were determined by FACS. Finally, carotid intima-media
      thickness (IMT) was measured by ultrasound. We observed that ICAM-1 expression by
      lymphocytes and serum sVCAM-1 levels were augmented at late postmenopause. Late
      postmenopause women with severe hot flashes had increased expression of CD62L and
      IL-8R on neutrophils. By multivariate analysis, the carotid IMT was strongly
      associated with membrane-bound TNF-alpha, CD11b expression, Annexin V(+) CD3(+)
      MPs, LPS-induced NO production, HDL-cholesterol and age. Depressive mood was
      associated negatively with PSGL-1 and positively with LPS-induced NO. Finally,
      Log(AMH) levels were associated with carotid IMT, IL-8R expression and time since
      menopause. IMT and depressive mood were the main clinical features related to
      vascular inflammation. Aging, hormonal changes and obesity were also related to
      endothelial dysfunction. These findings provide further evidence for a link
      between estrogen deficiency and low-grade inflammation in endothelial impairment
      in mature women.

PMID- 25993482
TI  - Can newts cope with the heat? Disparate thermoregulatory strategies of two
      sympatric species in water.
AB  - Many ectotherms effectively reduce their exposure to low or high environmental
      temperatures using behavioral thermoregulation. In terrestrial ectotherms,
      thermoregulatory strategies range from accurate thermoregulation to
      thermoconformity according to the costs and limits of thermoregulation, while in
      aquatic taxa the quantification of behavioral thermoregulation have received
      limited attention. We examined thermoregulation in two sympatric newt species,
      Ichthyosaura alpestris and Lissotriton vulgaris, exposed to elevated water
      temperatures under semi-natural conditions. According to a recent theory, we
      predicted that species for which elevated water temperatures pose a lower thermal
      quality habitat, would thermoregulate more effectively than species in thermally
      benign conditions. In the laboratory thermal gradient, L. vulgaris maintained
      higher body temperatures than I. alpestris. Semi-natural thermal conditions
      provided better thermal quality of habitat for L. vulgaris than for I. alpestris.
      Thermoregulatory indices indicated that I. alpestris actively thermoregulated its
      body temperature, whereas L. vulgaris remained passive to the thermal
      heterogeneity of aquatic environment. In the face of elevated water temperatures,
      sympatric newt species employed disparate thermoregulatory strategies according
      to the species-specific quality of the thermal habitat. Both strategies reduced
      newt exposure to suboptimal water temperatures with the same accuracy but with or
      without the costs of thermoregulation. The quantification of behavioral
      thermoregulation proves to be an important conceptual and methodological tool for
      thermal ecology studies not only in terrestrial but also in aquatic ectotherms. 

PMID- 25993481
TI  - A systematic review of childhood maltreatment assessments in population
      representative surveys since 1990.
AB  - BACKGROUND: Population-representative surveys that assess childhood maltreatment
      and health are a valuable resource to explore the implications of child
      maltreatment for population health. Systematic identification and evaluation of
      such surveys is needed to facilitate optimal use of their data and to inform
      future research. OBJECTIVES: To inform researchers of the existence and nature of
      population-representative surveys relevant to understanding links between
      childhood maltreatment and health; to evaluate the assessment of childhood
      maltreatment in this body of work. METHODS: We included surveys that: 1) were
      representative of the non-institutionalized population of any size nation or of
      any geopolitical region >= 10 million people; 2) included a broad age range (>=
      40 years); 3) measured health; 4) assessed childhood maltreatment
      retrospectively; and 5) were conducted since 1990. We used Internet and database
      searching (including CINAHL, Embase, ERIC, Global Health, MEDLINE, PsycINFO,
      Scopus, Social Policy and Practice: January 1990 to March 2014), expert
      consultation, and other means to identify surveys and associated documentation.
      Translations of non-English survey content were verified by fluent readers of
      survey languages. We developed checklists to abstract and evaluate childhood
      maltreatment content. RESULTS: Fifty-four surveys from 39 countries met inclusion
      criteria. Sample sizes ranged from 1,287-51,945 and response rates from 15%-96%.
      Thirteen surveys assessed neglect, 15 emotional abuse; 18 exposure to family
      violence; 26 physical abuse; 48 sexual abuse. Fourteen surveys assessed more than
      three types; six of these were conducted since 2010. In nine surveys childhood
      maltreatment assessments were detailed (+10 items for at least one type of
      maltreatment). Seven surveys' assessments had known reliability and/or validity.
      CONCLUSIONS AND IMPLICATIONS: Data from 54 surveys can be used to explore the
      population health relevance of child maltreatment. Assessment of childhood
      maltreatment is not comprehensive but there is evidence of recent improvement.

PMID- 25993483
TI  - Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated
      Cardiomyopathy.
AB  - BACKGROUND: Left atrial volume (LAV) is a predictor of prognosis in patients with
      heart failure. OBJECTIVE: We aimed to evaluate the determinants of LAV in
      patients with dilated cardiomyopathy (DCM). METHODS: Ninety patients with DCM and
      left ventricular (LV) ejection fraction <= 0.50 were included. LAV was measured
      with real-time three-dimensional echocardiography (eco3D). The variables
      evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and
      end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue
      Doppler e' wave, E/e' ratio, intraventricular dyssynchrony, 3D dyssynchrony index
      and mitral regurgitation vena contracta. Pearson's coefficient was used to
      identify the correlation of the LAV with the assessed variables. A multiple
      linear regression model was developed that included LAV as the dependent variable
      and the variables correlated with it as the predictive variables. RESULTS: Mean
      age was 52 +/- 11 years-old, LV ejection fraction: 31.5 +/- 8.0% (16-50%) and
      LAV: 39.2+/-15.7 ml/m2. The variables that correlated with the LAV were LV end
      diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p <
      0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01),
      E/e' ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A
      multivariate analysis identified the E/e' ratio (p = 0.02) and mitral
      regurgitation (p = 0.02) as the only independent variables associated with LAV
      increase. CONCLUSION: The LAV is independently determined by LV filling pressures
      (E/e' ratio) and mitral regurgitation in DCM.

PMID- 25993484
TI  - Metabolic Syndrome and Importance of Associated Variables in Children and
      Adolescents in Guabiruba - SC, Brazil.
AB  - BACKGROUND: The risk factors that characterize metabolic syndrome (MetS) may be
      present in childhood and adolescence, increasing the risk of cardiovascular
      disease in adulthood. OBJECTIVE: Evaluate the prevalence of MetS and the
      importance of its associated variables, including insulin resistance (IR), in
      children and adolescents in the city of Guabiruba-SC, Brazil. METHODS: Cross
      sectional study with 1011 students (6-14 years, 52.4% girls, 58.5% children).
      Blood samples were collected for measurement of biochemical parameters by routine
      laboratory methods. IR was estimated by the HOMA-IR index, and weight, height,
      waist circumference and blood pressure were determined. Multivariate logistic
      regression models were used to examine the associations between risk variables
      and MetS. RESULTS: The prevalence of MetS, IR, overweight and obesity in the
      cohort were 14%, 8.5%, 21% and 13%, respectively. Among students with MetS, 27%
      had IR, 33% were overweight, 45.5% were obese and 22% were eutrophic. IR was more
      common in overweight (48%) and obese (41%) students when compared with eutrophic
      individuals (11%; p = 0.034). The variables with greatest influence on the
      development of MetS were obesity (OR = 32.7), overweight (OR = 6.1), IR (OR =
      4.4; p <= 0.0001 for all) and age (OR = 1.15; p = 0.014). CONCLUSION: There was a
      high prevalence of MetS in children and adolescents evaluated in this study.
      Students who were obese, overweight or insulin resistant had higher chances of
      developing the syndrome.

PMID- 25993485
TI  - One-year Mortality after an Acute Coronary Event and its Clinical Predictors: The
      ERICO Study.
AB  - BACKGROUND: Information about post-acute coronary syndrome (ACS) survival have
      been mostly short-term findings or based on specialized, cardiology referral
      centers. OBJECTIVES: To describe one-year case-fatality rates in the Strategy of
      Registry of Acute Coronary Syndrome (ERICO) cohort, and to study baseline
      characteristics as predictors. METHODS: We analyzed data from 964 ERICO
      participants enrolled from February 2009 to December 2012. We assessed vital
      status by telephone contact and official death certificate searches. The cause of
      death was determined according to the official death certificates. We used log
      rank tests to compare the probabilities of survival across subgroups. We built
      crude and adjusted (for age, sex and ACS subtype) Cox regression models to study
      if the ACS subtype or baseline characteristics were independent predictors of all
      cause or cardiovascular mortality. RESULTS: We identified 110 deaths in the
      cohort (case-fatality rate, 12.0%). Age [Hazard ratio (HR) = 2.04 per 10 year
      increase; 95% confidence interval (95%CI) = 1.75-2.38], non-ST elevation
      myocardial infarction (HR = 3.82 ; 95%CI = 2.21-6.60) or ST elevation myocardial
      infarction (HR = 2.59; 95%CI = 1.38-4.89) diagnoses, and diabetes (HR = 1.78;
      95%CI = 1.20-2.63) were significant risk factors for all-cause mortality in the
      adjusted models. We found similar results for cardiovascular mortality. A
      previous coronary artery disease diagnosis was also an independent predictor of
      all-cause mortality (HR = 1.61; 95%CI = 1.04-2.50), but not for cardiovascular
      mortality. CONCLUSION: We found an overall one-year mortality rate of 12.0% in a
      sample of post-ACS patients in a community, non-specialized hospital in Sao
      Paulo, Brazil. Age, ACS subtype, and diabetes were independent predictors of poor
      one-year survival for overall and cardiovascular-related causes.

PMID- 25993486
TI  - Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy.
AB  - BACKGROUND: Chagas disease is a cause of dilated cardiomyopathy, and information
      about left atrial (LA) function in this disease still lacks. OBJECTIVE: To assess
      the different LA functions (reservoir, conduit and pump functions) and their
      correlation with the echocardiographic parameters of left ventricular (LV)
      systolic and diastolic functions. METHODS: 10 control subjects (CG), and patients
      with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG
      alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M
      mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler
      imaging. RESULTS: Reservoir function (Total Emptying Fraction: TEF): (p <0.0001),
      lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001).
      Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII
      (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump
      function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared
      to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative
      correlation of E/e' (average) with the reservoir and pump functions (TEF and
      AEF), and a positive correlation of e' (average) with s' wave (both septal and
      lateral walls) and the reservoir, conduit and pump LA functions. CONCLUSION: An
      impairment of LA functions in Chagas cardiomyopathy was observed.

PMID- 25993487
TI  - Evaluation of a commercial orthopaedic metal artefact reduction tool in radiation
      therapy of patients with head and neck cancer.
AB  - OBJECTIVE: To assess the image quality and dosimetric effects of the Philips
      orthopaedic metal artefact reduction (OMAR) (Philips Healthcare System,
      Cleveland, OH) function for reducing metal artefacts on CT images of head and
      neck (H&N) patients. METHODS: 11 patients and a custom-built phantom with metal
      bead inserts (alumina, titanium, zirconia and chrome) were scanned. The image was
      reconstructed in two ways: with and without OMAR (OMAR and non-OMAR image). The
      mean and standard deviation values of CT Hounsfield unit (HU) for selected
      regions of interest of each case were investigated for both images. Volumetric
      modulated arc therapy plans were generated for all cases. Gamma analysis of each
      dose distribution pair in the patient (1%/1 mm criteria) and phantom (2%/2 mm and
      3%/3 mm criteria) images was performed. The film measurements in phantom for two
      metal beads were conducted for evaluating the calculated dose on both OMAR and
      non-OMAR images. RESULTS: In the OMAR images, noise values were generally
      reduced, and the mean HU became closer to the reference value (measured from
      patients without metal implants) in both patient and phantom cases. Although
      dosimetric difference was insignificant for the eight closed-mouth patients
      (gamma = 99.4 +/- 0.5%), there was a large discrepancy in dosimetric calculation
      between OMAR and non-OMAR images for the three opened-mouth patients (gamma =
      91.1%, 94.8% and 96.6%). Moreover, the calculated dose on the OMAR image is
      closer to the real delivered dose on a radiochromic film than was the dose from
      the non-OMAR image. CONCLUSION: The OMAR algorithm increases the accuracy of CT
      HU and reduces the noise such that the entire radiation treatment planning
      process can be improved, especially for contouring and segmentation. ADVANCES IN
      KNOWLEDGE: OMAR reconstruction is appropriate for the radiotherapy planning
      process of H&N patients, particularly of patients who use a bite block.

PMID- 25993488
TI  - Does a too risk-averse approach to the implementation of new radiotherapy
      technologies delay their clinical use?
AB  - Radiotherapy is a generally safe treatment modality in practice; nevertheless,
      recent well-reported accidents also confirm its potential risks. However, this
      may obstruct or delay the introduction of new technologies and treatment
      strategies/techniques into clinical practice. Risks must be addressed and judged
      in a realistic context: risks must be assessed realistically. Introducing new
      technology may introduce new possibilities of errors. However, delaying the
      introduction of such new technology therefore means that patients are denied the
      potentially better treatment opportunities. Despite the difficulty in
      quantitatively assessing the risks on both sides of the possible choice of
      actions, including the "lost opportunity", the best estimates should be included
      in the overall risk-benefit and cost-benefit analysis. Radiotherapy requires a
      sufficiently high level of support for the safety, precision and accuracy
      required: radiotherapy development and implementation is exciting. However, it
      has been anxious with a constant awareness of the consequences of mistakes or
      misunderstandings. Recent history can be used to show that for introduction of
      advanced radiotherapy, the risk-averse medical physicist can act as an electrical
      fuse in a complex circuit. The lack of sufficient medical physics resource or
      expertise can short out this fuse and leave systems unsafe. Future technological
      developments will continue to present further safety and risk challenges. The
      important evolution of radiotherapy brings different management opinions and
      strategies. Advanced radiotherapy technologies can and should be safely
      implemented in as timely a manner as possible for the patient groups where
      clinical benefit is indicated. 

PMID- 25993489
TI  - Imaging Ca2+ dynamics in cone photoreceptor axon terminals of the mouse retina.
AB  - Retinal cone photoreceptors (cones) serve daylight vision and are the basis of
      color discrimination. They are subject to degeneration, often leading to
      blindness in many retinal diseases. Calcium (Ca(2+)), a key second messenger in
      photoreceptor signaling and metabolism, has been proposed to be indirectly linked
      with photoreceptor degeneration in various animal models. Systematically studying
      these aspects of cone physiology and pathophysiology has been hampered by the
      difficulties of electrically recording from these small cells, in particular in
      the mouse where the retina is dominated by rod photoreceptors. To circumvent this
      issue, we established a two-photon Ca(2+) imaging protocol using a transgenic
      mouse line that expresses the genetically encoded Ca(2+) biosensor TN-XL
      exclusively in cones and can be crossbred with mouse models for photoreceptor
      degeneration. The protocol described here involves preparing vertical sections
      ("slices") of retinas from mice and optical imaging of light stimulus-evoked
      changes in cone Ca(2+) level. The protocol also allows "in-slice measurement" of
      absolute Ca(2+) concentrations; as the recordings can be followed by calibration.
      This protocol enables studies into functional cone properties and is expected to
      contribute to the understanding of cone Ca(2+) signaling as well as the potential
      involvement of Ca(2+) in photoreceptor death and retinal degeneration. 

PMID- 25993491
TI  - Impact of Malaria Vector Control Interventions at the Beginning of a Malaria
      Elimination Stage in a Dominant Area of Anopheles anthropophagus, Hubei Province,
      China.
AB  - Three towns with similar socio-ecological characteristics, malaria morbidities,
      and populations were selected for this study to explore economic and effective
      malaria control measures.The sources of infection were controlled in each town.
      Impregnated mosquito nets with 2.5% deltamethrin (15 mg/m(2)) combined with
      residual spraying of 5% cypermethrin (25 mg/m(2)) was implemented in cattle and
      pig pens, as well as in crowded sites in Chenji, whereas the mosquito nets were
      treated with 2.5% deltamethrin only in Guanqiao Town. All the control measures
      implemented in Fengling (control town) were the same as those implemented in the
      towns of Chenji and Guanqiao, except for mosquito elimination control. Results
      were evaluated and compared based on pathogens and entomology. The densities of
      Anopheles anthropophagus mosquitoes in houses, outside houses (man bait), as well
      as in cattle pens and pig pens were reduced by 100%, 71.96%, 94.01%, and 67.42%,
      respectively at all 4 sites in Chenji Town, whereas the density increased at 1
      site (the outside house [man bait]) by 12.38%, while the densities at the other 3
      sites (in houses, cattle pens and pig pens) were reduced by 99.63%, 18.71% and
      69.44% respectively in Guanqiao Town. The biting rates of An. anthropophagus in
      the 3 towns were 0.11, 0.22, and 1.1 respectively in Chenji, Guanqiao, and
      Fengling. The incidence of malaria in the 3 towns decreased by 73.12%, 57.71%,
      and 65.71% in terms of annual average. Both impregnated mosquito nets combined
      with residual spraying and impregnated mosquito nets only reduced the density of
      An. anthropophagus in houses in the 2 towns, but reduction was more rapid in
      Chenji Town. 

PMID- 25993490
TI  - Measurement of extracellular ion fluxes using the ion-selective self-referencing
      microelectrode technique.
AB  - Cells from animals, plants and single cells are enclosed by a barrier called the
      cell membrane that separates the cytoplasm from the outside. Cell layers such as
      epithelia also form a barrier that separates the inside from the outside or
      different compartments of multicellular organisms. A key feature of these
      barriers is the differential distribution of ions across cell membranes or cell
      layers. Two properties allow this distribution: 1) membranes and epithelia
      display selective permeability to specific ions; 2) ions are transported through
      pumps across cell membranes and cell layers. These properties play crucial roles
      in maintaining tissue physiology and act as signaling cues after damage, during
      repair, or under pathological condition. The ion-selective self-referencing
      microelectrode allows measurements of specific fluxes of ions such as calcium,
      potassium or sodium at single cell and tissue levels. The microelectrode contains
      an ionophore cocktail which is selectively permeable to a specific ion. The
      internal filling solution contains a set concentration of the ion of interest.
      The electric potential of the microelectrode is determined by the outside
      concentration of the ion. As the ion concentration varies, the potential of the
      microelectrode changes as a function of the log of the ion activity. When moved
      back and forth near a source or sink of the ion (i.e. in a concentration gradient
      due to ion flux) the microelectrode potential fluctuates at an amplitude
      proportional to the ion flux/gradient. The amplifier amplifies the microelectrode
      signal and the output is recorded on computer. The ion flux can then be
      calculated by Fick's law of diffusion using the electrode potential fluctuation,
      the excursion of microelectrode, and other parameters such as the specific ion
      mobility. In this paper, we describe in detail the methodology to measure
      extracellular ion fluxes using the ion-selective self-referencing microelectrode
      and present some representative results. 

PMID- 25993493
TI  - SnO2 Nanosheet/Nanoparticle Detector for the Sensing of 1-Nonanal Gas Produced by
      Lung Cancer.
AB  - A sensor has been developed for detecting 1-nonanal gas present in the breath of
      lung cancer patients by combining SnO2 nanosheets with SnO2 nanoparticles and
      noble metal catalysts. A significant change in the electrical resistance of this
      sensor was observed with increasing 1-nonanal gas concentration; the resistance
      decreased by a factor of 1.12 within the range of 1 to 10 ppm at 300  degrees C.
      The recovery of the sensor's resistance after detecting 1-nonanal gas
      concentrations of 0.055, 0.18, 1, and 9.5 ppm was determined to be 86.1, 84.2,
      80.4 and 69.2%, respectively. This high sensitivity is attributed to the
      accelerated oxidation of 1-nonanal molecules caused by the (101) crystal faces of
      the SnO2 nanosheets and should provide a simple and effective approach to the
      early detection of lung cancer.

PMID- 25993492
TI  - Two Patterns of White Matter Abnormalities in Medication-Naive Patients With
      First-Episode Schizophrenia Revealed by Diffusion Tensor Imaging and Cluster
      Analysis.
AB  - IMPORTANCE: Accumulating evidence supports the hypothesis that cerebral white
      matter abnormalities are involved in the pathophysiology of schizophrenia;
      however, findings from in vivo neuroimaging studies have been inconsistent.
      Besides confounding factors, including age, illness duration, and medication
      effects, an additional cause for the inconsistent results may be heterogeneity in
      the nature of white matter alterations associated with the disorder. OBJECTIVE:
      To investigate whether different patterns of white matter abnormalities exist in
      a large cohort of medication-naive patients with first-episode schizophrenia and
      the relationship between such patterns and clinical parameters. DESIGN, SETTING,
      AND PARTICIPANTS: A cross-sectional diffusion tensor imaging study of 113
      medication-naive patients with first-episode schizophrenia and 110
      demographically matched healthy control individuals. The study was conducted in
      the mental health center of West China Hospital, Sichuan University, Chengdu,
      China, from January 2006 to June 2014. MAIN OUTCOMES AND MEASURES: The patterns
      of white matter abnormalities revealed by tract-specific analysis in conjunction
      with hierarchical clustering. RESULTS: With diffusion features extracted from 18
      fiber tracts, cluster analysis revealed 2 patterns of abnormalities. One pattern
      (42.5% of patient sample) showed widespread white matter abnormalities compared
      with matched healthy control individuals, while another pattern (57.5% of patient
      sample) only showed circumscribed regional white matter abnormalities, mainly in
      the left superior longitudinal fasciculus. Patients in these subgroups did not
      differ in demographic features; however, negative symptoms were more severe in
      patients with widespread white matter abnormalities. CONCLUSIONS AND RELEVANCE:
      Two distinct patterns of white matter abnormalities exist at the early phase of
      schizophrenia, with those having global abnormalities experiencing more severe
      negative symptoms. The finding that distinct subgroups of patients with
      schizophrenia have different forms of white matter pathology may reflect
      qualitatively distinct genetic influences or neurodevelopmental alterations and
      thus represents a promising strategy for resolving neurobiological heterogeneity
      in the schizophrenia syndrome.

PMID- 25993495
TI  - Three-dimensional (3D) tumor spheroid invasion assay.
AB  - Invasion of surrounding normal tissues is generally considered to be a key
      hallmark of malignant (as opposed to benign) tumors. For some cancers in
      particular (e.g., brain tumors such as glioblastoma multiforme and squamous cell
      carcinoma of the head and neck - SCCHN) it is a cause of severe morbidity and can
      be life-threatening even in the absence of distant metastases. In addition,
      cancers which have relapsed following treatment unfortunately often present with
      a more aggressive phenotype. Therefore, there is an opportunity to target the
      process of invasion to provide novel therapies that could be complementary to
      standard anti-proliferative agents. Until now, this strategy has been hampered by
      the lack of robust, reproducible assays suitable for a detailed analysis of
      invasion and for drug screening. Here we provide a simple micro-plate method
      (based on uniform, self-assembling 3D tumor spheroids) which has great potential
      for such studies. We exemplify the assay platform using a human glioblastoma cell
      line and also an SCCHN model where the development of resistance against targeted
      epidermal growth factor receptor (EGFR) inhibitors is associated with enhanced
      matrix-invasive potential. We also provide two alternative methods of semi
      automated quantification: one using an imaging cytometer and a second which
      simply requires standard microscopy and image capture with digital image
      analysis. 

PMID- 25993494
TI  - Intratracheally instilled titanium dioxide nanoparticles translocate to heart and
      liver and activate complement cascade in the heart of C57BL/6 mice.
AB  - An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate
      to systemic circulation and enter other organs; however, this estimation may not
      be accurate given the low sensitivity of existing in vivo NP detection methods.
      Moreover, the biological effects of such low levels of translocation are unclear.
      We employed a nano-scale hyperspectral microscope to spatially observe and
      spectrally profile NPs in tissues and blood following pulmonary deposition in
      mice. In addition, we characterized effects occurring in blood, liver and heart
      at the mRNA and protein level following translocation from the lungs. Adult
      female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 ug
      of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside
      vehicle controls. Using the nano-scale hyperspectral microscope, translocation to
      heart and liver was confirmed at both doses, and to blood at the highest dose, in
      mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA
      analysis revealed activation of complement cascade and inflammatory processes in
      heart and specific activation of complement factor 3 in blood, suggesting
      activation of an early innate immune response essential for particle opsonisation
      and clearance. The liver showed a subtle response with changes in the expression
      of genes associated with acute phase response. This study characterizes the
      subtle systemic effects that occur in liver and heart tissues following pulmonary
      exposure and low levels of translocation of nano-TiO2 from lungs. 

PMID- 25993496
TI  - alpha- and beta-Santalols Directly Interact with Tubulin and Cause Mitotic Arrest
      and Cytotoxicity in Oral Cancer Cells.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide, with no major advancements in treatment over the past 40 years. The
      current study explores the biological effects of East Indian sandalwood oil
      (EISO) and its two major constituents, alpha- and beta-santalol, against a
      variety of HNSCC lines. All three agents exhibited cytotoxic effects and caused
      accumulation of cells in the G2/M phases of the cell cycle. Additionally,
      treatment with these agents caused formation of multipolar mitotic spindles
      similar to those observed upon treatment of cells with compounds that affect
      microtubule polymerization. Indeed, the santalols, as well as EISO, inhibited the
      polymerization of purified tubulin, indicating for the first time that these
      compounds have the ability to directly bind to tubulin and affect microtubule
      formation. Modeling studies suggest that the santalols can weakly bind to the
      colchicine site on tubulin, and topical administration of EISO to a HNSCC
      xenograft inhibited tumor growth with no observed toxicities. Therefore,
      santalols can directly interact with tubulin to inhibit the polymerization of
      microtubules, similarly to established classes of chemotherapeutic agents, albeit
      with greatly reduced potency that is not associated with the classic toxicity
      associated with most other compounds that interact directly with tubulin. 

PMID- 25993497
TI  - A two-parameter extension of classical nucleation theory.
AB  - A two-variable stochastic model for diffusion-limited nucleation is developed
      using a formalism derived from fluctuating hydrodynamics. The model is a direct
      generalization of the standard classical nucleation theory (CNT). The nucleation
      rate and pathway are calculated in the weak-noise approximation and are shown to
      be in good agreement with direct numerical simulations for the weak
      solution/strong-solution transition in globular proteins. We find that CNT
      underestimates the time needed for the formation of a critical cluster by two
      orders of magnitude and that this discrepancy is due to the more complex dynamics
      of the two variable model and not, as often is assumed, a result of errors in the
      estimation of the free energy barrier. 

PMID- 25993498
TI  - Efficient spatio-temporal local binary patterns for spontaneous facial micro
      expression recognition.
AB  - Micro-expression recognition is still in the preliminary stage, owing much to the
      numerous difficulties faced in the development of datasets. Since micro
      expression is an important affective clue for clinical diagnosis and deceit
      analysis, much effort has gone into the creation of these datasets for research
      purposes. There are currently two publicly available spontaneous micro-expression
      datasets--SMIC and CASME II, both with baseline results released using the widely
      used dynamic texture descriptor LBP-TOP for feature extraction. Although LBP-TOP
      is popular and widely used, it is still not compact enough. In this paper, we
      draw further inspiration from the concept of LBP-TOP that considers three
      orthogonal planes by proposing two efficient approaches for feature extraction.
      The compact robust form described by the proposed LBP-Six Intersection Points
      (SIP) and a super-compact LBP-Three Mean Orthogonal Planes (MOP) not only
      preserves the essential patterns, but also reduces the redundancy that affects
      the discriminality of the encoded features. Through a comprehensive set of
      experiments, we demonstrate the strengths of our approaches in terms of
      recognition accuracy and efficiency.

PMID- 25993499
TI  - Cloning and Functional Analysis of Histones H3 and H4 in Nuclear Shaping during
      Spermatogenesis of the Chinese Mitten Crab, Eriocheir sinensis.
AB  - During spermatogenesis in most animals, the basic proteins associated with DNA
      are continuously changing and somatic-typed histones are partly replaced by sperm
      specific histones, which are then successively replaced by transition proteins
      and protamines. With the replacement of sperm nuclear basic proteins, nuclei
      progressively undergo chromatin condensation. The Chinese Mitten Crab (Eriocheir
      sinensis) is also known as the hairy crab or river crab (phylum Arthropoda,
      subphylum Crustacea, order Decapoda, and family Grapsidae). The spermatozoa of
      this species are aflagellate, and each has a spherical acrosome surrounded by a
      cup-shaped nucleus, peculiar to brachyurans. An interesting characteristic of the
      E. sinensis sperm nucleus is its lack of electron-dense chromatin. However, its
      formation is not clear. In this study, sequences encoding histones H3 and H4 were
      cloned by polymerase chain reaction amplification. Western blotting indicated
      that H3 and H4 existed in the sperm nuclei. Immunofluorescence and
      ultrastructural immunocytochemistry demonstrated that histones H3 and H4 were
      both present in the nuclei of spermatogonia, spermatocytes, spermatids and mature
      spermatozoa. The nuclear labeling density of histone H4 decreased in sperm
      nuclei, while histone H3 labeling was not changed significantly. Quantitative
      real-time PCR showed that the mRNA expression levels of histones H3 and H4 were
      higher at mitotic and meiotic stages than in later spermiogenesis. Our study
      demonstrates that the mature sperm nuclei of E. sinensis contain histones H3 and
      H4. This is the first report that the mature sperm nucleus of E. sinensis
      contains histones H3 and H4. This finding extends the study of sperm histones of
      E. sinensis and provides some basic data for exploring how decapod crustaceans
      form uncondensed sperm chromatin. 

PMID- 25993500
TI  - Phonon Engineering in Isotopically Disordered Silicon Nanowires.
AB  - The introduction of stable isotopes in the fabrication of semiconductor nanowires
      provides an additional degree of freedom to manipulate their basic properties,
      design an entirely new class of devices, and highlight subtle but important
      nanoscale and quantum phenomena. With this perspective, we report on phonon
      engineering in metal-catalyzed silicon nanowires with tailor-made isotopic
      compositions grown using isotopically enriched silane precursors (28)SiH4,
      (29)SiH4, and (30)SiH4 with purity better than 99.9%. More specifically,
      isotopically mixed nanowires (28)Si(x)(30)Si(1-x) with a composition close to the
      highest mass disorder (x ~ 0.5) were investigated. The effect of mass disorder on
      the phonon behavior was elucidated and compared to that in isotopically pure
      (29)Si nanowires having a similar reduced mass. We found that the disorder
      induced enhancement in phonon scattering in isotopically mixed nanowires is
      unexpectedly much more significant than in bulk crystals of close isotopic
      compositions. This effect is explained by a nonuniform distribution of (28)Si and
      (30)Si isotopes in the grown isotopically mixed nanowires with local compositions
      ranging from x = ~0.25 to 0.70. Moreover, we also observed that upon heating,
      phonons in (28)Si(x)(30)Si(1-x) nanowires behave remarkably differently from
      those in (29)Si nanowires suggesting a reduced thermal conductivity induced by
      mass disorder. Using Raman nanothermometry, we found that the thermal
      conductivity of isotopically mixed (28)Si(x)(30)Si(1-x) nanowires is ~30% lower
      than that of isotopically pure (29)Si nanowires in agreement with theoretical
      predictions.

PMID- 25993502
TI  - Special issue on Chagas disease.

PMID- 25993501
TI  - Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth
      Infections in HIV-Infected Patients in Lambarene, Gabon.
AB  - BACKGROUND: Foci of the HIV epidemic and helminthic infections largely overlap
      geographically. Treatment options for helminth infections are limited, and there
      is a paucity of drug-development research in this area. Limited evidence suggests
      that antiretroviral therapy (ART) reduces prevalence of helminth infections in
      HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole
      preventive therapy (CTX-P) is associated with a reduced prevalence of helminth
      infections. METHODOLOGY AND PRINCIPAL FINDINGS: This cross-sectional study was
      conducted at a primary HIV-clinic in Lambarene, Gabon. HIV-infected adults who
      were ART-naive or exposed to ART for at least 3 months submitted one blood sample
      and stool and urine samples on 3 consecutive days. Outcome was helminth infection
      with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella
      perstans. Multivariable logistic regression was used to assess associations
      between ART or CTX-P and helminth infection. In total, 408 patients were
      enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections
      were most prevalent (55/310 [17.7%]), followed by infection with intestinal
      helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P
      had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95%
      CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95%
      CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth
      infection prevalence. CONCLUSIONS/SIGNIFICANCE: CTX-P use was associated with a
      decreased risk of Loa loa infection, suggesting an anthelminthic effect of
      antifolate drugs. No relation between ART use and helminth infections was
      established.

PMID- 25993503
TI  - Integrated control of Chagas disease for its elimination as public health problem
      -a review.
AB  - Chagas disease or American trypanosomiasis is, together with geohelminths, the
      neglected disease that causes more loss of years of healthy life due to
      disability in Latin America. Chagas disease, as determined by the factors and
      determinants, shows that different contexts require different actions, preventing
      new cases or reducing the burden of disease. Control strategies must combine two
      general courses of action including prevention of transmission to prevent the
      occurrence of new cases (these measures are cost effective), as well as opportune
      diagnosis and treatment of infected individuals in order to prevent the clinical
      evolution of the disease and to allow them to recuperate their health. All
      actions should be implemented as fully as possible and with an integrated way, to
      maximise the impact. Chagas disease cannot be eradicated due because of the
      demonstrated existence of infected wild triatomines in permanent contact with
      domestic cycles and it contributes to the occurrence of at least few new cases.
      However, it is possible to interrupt the transmission of Trypanosoma cruzi in a
      large territory and to eliminate Chagas disease as a public health problem with a
      dramatic reduction of burden of the disease.

PMID- 25993505
TI  - Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of
      Chagas disease.
AB  - Chagas disease is one of the most important yet neglected parasitic diseases in
      Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine
      species have been consistently found to invade human houses and all have been
      found to be naturally infected with Trypanosoma cruzi. The present paper aims to
      produce a state-of-knowledge atlas of Mexican triatomines and analyse their
      geographic associations with T. cruzi, human demographics and landscape
      modification. Ecological niche models (ENMs) were constructed for the 19 species
      with more than 10 records in North America, as well as for T. cruzi. The 2010
      Mexican national census and the 2007 National Forestry Inventory were used to
      analyse overlap patterns with ENMs. Niche breadth was greatest in species from
      the semiarid Nearctic Region, whereas species richness was associated with
      topographic heterogeneity in the Neotropical Region, particularly along the
      Pacific Coast. Three species, Triatoma longipennis, Triatoma mexicana and
      Triatoma barberi, overlapped with the greatest numbers of human communities, but
      these communities had the lowest rural/urban population ratios. Triatomine
      vectors have urbanised in most regions, demonstrating a high tolerance to human
      modified habitats and broadened historical ranges, exposing more than 88% of the
      Mexican population and leaving few areas in Mexico without the potential for T.
      cruzi transmission.

PMID- 25993506
TI  - Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211
      individuals born to infected mothers.
AB  - Transmission of Trypanosoma cruzi during pregnancy is estimated to occur in less
      than 20% of infected mothers; however, the etiopathogenesis is not completely
      understood. The Centre for Studies on Chagas Disease provides confirmation of T.
      cruzi infection for individuals living in central Brazil. In this retrospective
      hospital-based study, all requests for diagnosis of T. cruzi infection in
      individuals less than 21 years old from 1994-2014 were searched. We end with
      1,211 individuals and their respective infected mothers. Congenital transmission
      of infection was confirmed in 24 individuals (2%) in central Brazil, an area
      where the main T. cruzi lineage circulating in humans is TcII. This low
      prevalence of congenital Chagas disease is discussed in relation to recent
      findings in the south region of Brazil, where TcV is the main lineage and
      congenital transmission has a higher prevalence (approximately 5%), similar to
      frequencies reported in Argentina, Paraguay and Bolivia. This is the first report
      to show geographical differences in the rates of congenital transmission of T.
      cruzi and the relationship between the prevalence of congenital transmission and
      the type of Tc prevalent in each region.

PMID- 25993504
TI  - Intrusive versus domiciliated triatomines and the challenge of adapting vector
      control practices against Chagas disease.
AB  - Chagas disease prevention remains mostly based on triatomine vector control to
      reduce or eliminate house infestation with these bugs. The level of adaptation of
      triatomines to human housing is a key part of vector competence and needs to be
      precisely evaluated to allow for the design of effective vector control
      strategies. In this review, we examine how the domiciliation/intrusion level of
      different triatomine species/populations has been defined and measured and
      discuss how these concepts may be improved for a better understanding of their
      ecology and evolution, as well as for the design of more effective control
      strategies against a large variety of triatomine species. We suggest that a major
      limitation of current criteria for classifying triatomines into sylvatic,
      intrusive, domiciliary and domestic species is that these are essentially
      qualitative and do not rely on quantitative variables measuring population
      sustainability and fitness in their different habitats. However, such assessments
      may be derived from further analysis and modelling of field data. Such approaches
      can shed new light on the domiciliation process of triatomines and may represent
      a key tool for decision-making and the design of vector control interventions.

PMID- 25993508
TI  - CO2 Absorption in an Alcoholic Solution of Heavily Hindered Alkanolamine:
      Reaction Mechanism of 2-(tert-Butylamino)ethanol with CO2 Revisited.
AB  - To advance the optimal design of amines for postcombustion CO2 capture, a sound
      mechanistic understanding of the chemical process of amines with good CO2 capture
      performance is advantageous. A sterically hindered alkanolamine, 2-(tert
      butylamino)ethanol (TBAE), in ethylene glycol (EG) solution was recently reported
      to have better CO2 capture performance and unusual reactivity toward CO2, in
      comparison with those of the prototypical alkanolamines. However, the reaction
      mechanism of TBAE with CO2 in EG solution is unclear. Here, various quantum
      chemistry methods were employed to probe the reaction mechanism of TBAE with CO2
      in EG and aqueous solution. Six reaction pathways involving three kinds of
      possible reactive centers of TBAE solution were considered. The results indicated
      that the formation of anionic hydroxyethyl carbonate by the attack of -OH of EG
      on CO2 is the most favorable, which is confirmed by complementary high-resolution
      mass spectrum experiments. This clarified that the speculated zwitterionic
      carbonate species is not the main product in EG solution. The reaction process of
      TBAE in aqueous solution is similar to that in EG solution, leading to
      bicarbonate, which agrees with experimental observations. On the basis of the
      unveiled reaction mechanisms of TBAE + CO2, the role of the key tert-butyl
      functional group of TBAE was revealed. 

PMID- 25993507
TI  - Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for
      chronic Chagas disease.
AB  - The aim of this review is to describe the contributions of the knowledge of T
      cell responses to the understanding of the physiopathology and the responsiveness
      to etiological treatment during the chronic phase of Chagas disease. T-helper
      (Th)1 and interleukin (IL)-10 Trypanosoma cruzi-specific T-cells have been linked
      to the asymptomatic phase or to severe clinical forms of the disease,
      respectively or vice versa, depending on the T. cruzi antigen source, the
      patient's location and the performed immunological assays. Parasite-specific T
      cell responses are modulated after benznidazole (BZ) treatment in chronically T.
      cruzi-infected subjects in association with a significant decrease in T. cruzi
      specific antibodies. Accumulating evidence has indicated that treatment efficacy
      during experimental infection with T. cruzi results from the combined action of
      BZ and the activation of appropriate immune responses in the host. However,
      strong support of this interaction in T. cruzi-infected humans remains lacking.
      Overall, the quality of T-cell responses might be a key factor in not only
      disease evolution, but also chemotherapy responsiveness. Immunological parameters
      are potential indicators of treatment response regardless of achievement of cure.
      Providing tools to monitor and provide early predictions of treatment success
      will allow the development of new therapeutic options.

PMID- 25993509
TI  - The effects of neat biodiesel and biodiesel and HVO blends in diesel fuel on
      exhaust emissions from a light duty vehicle with a diesel engine.
AB  - The influence of fatty acid methyl esters (FAME) and hydrotreated vegetable oil
      (HVO) diesel blends on the exhaust emissions from a passenger car was examined.
      The impact of FAME for the cold urban phase (UDC) was increased CO and HC
      emissions, probably due to blend physical properties promoting incomplete
      combustion. The HVO blend caused the lowest CO and HC emissions for the UDC. NOx
      emissions did not change significantly with the fuel used, however the UDC was
      characterized by lower NOx emission for FAME blends. Particle emissions were
      highest with standard diesel. Emissions of carbonyl compounds increased as fuel
      biodiesel content increased, especially during the UDC. HVO in diesel fuel
      decreased carbonyl emissions. Formaldehyde and acetaldehyde were the most
      abundant carbonyl compounds in the exhaust gas. Total particle-bound PAH
      emissions were variable, the emission of heavier PAHs increased with blend
      biodiesel content. The HVO blend increased emission of lighter PAHs. Nitro-PAHs
      were identified only during the UDC and not for all blends; the highest emissions
      were measured for pure diesel. The results showed that emission of nitro-PAHs may
      be decreased to a greater extent by using biodiesel than using a HVO blend.

PMID- 25993511
TI  - Light-Driven and Phonon-Assisted Dynamics in Organic and Semiconductor
      Nanostructures.

PMID- 25993510
TI  - Reciprocal regulation of C-Maf tyrosine phosphorylation by Tec and Ptpn22.
AB  - C-Maf plays an important role in regulating cytokine production in TH cells. Its
      transactivation of IL-4 is optimized by phosphorylation at Tyr21, Tyr92, and
      Tyr131. However, the molecular mechanism regulating its tyrosine phosphorylation
      remains unknown. In this study, we demonstrate that Tec kinase family member Tec,
      but not Rlk or Itk, is a tyrosine kinase of c-Maf and that Tec enhances c-Maf
      dependent IL-4 promoter activity. This effect of Tec is counteracted by Ptpn22,
      which physically interacts with and facilitates tyrosine dephosphorylation of c
      Maf thereby attenuating its transcriptional activity. We further show that
      phosphorylation of Tyr21/92/131 of c-Maf is also critical for its recruitment to
      the IL-21 promoter and optimal production of this cytokine by TH17 cells. Thus,
      manipulating tyrosine phosphorylation of c-Maf through its kinases and
      phosphatases can have significant impact on TH cell-mediated immune responses. 

PMID- 25993512
TI  - Buoyancy-activated cell sorting using targeted biotinylated albumin microbubbles.
AB  - Cell analysis often requires the isolation of certain cell types. Various
      isolation methods have been applied to cell sorting, including fluorescence
      activated cell sorting and magnetic-activated cell sorting. However, these
      conventional approaches involve exerting mechanical forces on the cells, thus
      risking cell damage. In this study we applied a novel isolation method called
      buoyancy-activated cell sorting, which involves using biotinylated albumin
      microbubbles (biotin-MBs) conjugated with antibodies (i.e., targeted biotin-MBs).
      Albumin MBs are widely used as contrast agents in ultrasound imaging due to their
      good biocompatibility and stability. For conjugating antibodies, biotin is
      conjugated onto the albumin MB shell via covalent bonds and the biotinylated
      antibodies are conjugated using an avidin-biotin system. The albumin microbubbles
      had a mean diameter of 2 MUm with a polydispersity index of 0.16. For cell
      separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs
      conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then
      allowed 1 hour at 4  degrees C for separation. The results indicate that targeted
      biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB
      231 breast cancer cells; more than 90% of the cells were collected in the MB
      layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we
      found that the separating efficiency was higher for targeted biotin-MBs than for
      targeted avidin-incorporated albumin MBs (avidin-MBs), which is the most common
      way to make targeted albumin MBs. We also demonstrated that the recovery rate of
      targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for
      a a heterogenous cell population containing MDA-MB-231 cells (CD44(+)) and MDA-MB
      453 cells (CD44-), which are classified as basal-like breast cancer cells and
      luminal breast cancer cells, respectively. Knowing that the CD44(+) is a commonly
      used cancer-stem-cell biomarker, our targeted biotin-MBs could be a potent tool
      to sort cancer stem cells from dissected tumor tissue for use in preclinical
      experiments and clinical trials.

PMID- 25993513
TI  - Studying the effects of reproductive hormones and bacterial vaginosis on the
      glycome of lavage samples from the cervicovaginal cavity.
AB  - The cervicovaginal fluid (CVF) coating the vaginal epithelium is an important
      immunological mediator, providing a barrier to infection. Glycosylation of CVF
      proteins, such as mucins, IgG and S-IgA, plays a critical role in their
      immunological functions. Although multiple factors, such as hormones and
      microflora, may influence glycosylation of the CVF, few studies have examined
      their impact on this important immunological fluid. Herein we analyzed the
      glycosylation of cervicovaginal lavage (CVL) samples collected from 165 women
      under different hormonal conditions including: (1) no contraceptive, post
      menopausal, (2) no contraceptive, days 1-14 of the menstrual cycle, (3) no
      contraceptive, days 15-28 of the menstrual cycle, (4) combined-oral contraceptive
      pills for at least 6 months, (5) depo-medroxyprogesterone acetate (Depo-Provera)
      injections for at least 6 months, (6) levonorgestrel IUD for at least 1 month.
      Glycomic profiling was obtained using our lectin microarray system, a rapid
      method to analyze carbohydrate composition. Although some small effects were
      observed due to hormone levels, the major influence on the glycome was the
      presence of an altered bacterial cohort due to bacterial vaginosis (BV). Compared
      to normal women, samples from women with BV contained lower levels of sialic acid
      and high-mannose glycans in their CVL. The change in high mannose levels was
      unexpected and may be related to the increased risk of HIV-infection observed in
      women with BV, as high mannose receptors are a viral entry pathway. Changes in
      the glycome were also observed with hormonal contraceptive use, in a
      contraceptive-dependent manner. Overall, microflora had a greater impact on the
      glycome than hormonal levels, and both of these effects should be more closely
      examined in future studies given the importance of glycans in the innate immune
      system. 

PMID- 25993514
TI  - Positive selection of natural poly-reactive B cells in the periphery occurs
      independent of heavy chain allelic inclusion.
AB  - Natural autoreactive B cells are important mediators of autoimmune diseases.
      Receptor editing is known to play an important role in both central and
      peripheral B cell tolerance. However, the role of allelic inclusion in the
      development of natural autoreactive B cells is not clear. Previously, we
      generated MU chain (TgV(H)3B4I) and MU/kappa chains (TgV(H/L)3B4) transgenic mice
      using transgene derived from the 3B4 hybridoma, which produce poly-reactive
      natural autoantibodies. In this study, we demonstrate that a considerable
      population of B cells edited their B cells receptors (BCRs) via light chain or
      heavy chain allelic inclusion during their development in TgV(H)3B4I mice.
      Additionally, allelic inclusion occurred more frequently in the periphery and
      promoted the differentiation of B cells into marginal zone or B-1a cells in
      TgV(H)3B4I mice. B cells from TgV(H/L)3B4 mice expressing the intact transgenic
      3B4 BCR without receptor editing secreted poly-reactive 3B4 antibody.
      Interestingly, however, B cell that underwent allelic inclusion in TgV(H)3B4I
      mice also produced poly-reactive autoantibodies in vivo and in vitro. Our
      findings suggest that receptor editing plays a minor role in the positive
      selection of B cells expressing natural poly-reactive BCRs, which can be
      positively selected through heavy chain allelic inclusion to retain their poly
      reactivity in the periphery.

PMID- 25993515
TI  - Indoor Tracking to Understand Physical Activity and Sedentary Behaviour:
      Exploratory Study in UK Office Buildings.
AB  - Little is known of the patterns of physical activity, standing and sitting by
      office workers. However, insight into these behaviours is of growing interest,
      notably in regard to public health priorities to reduce non-communicable disease
      risk factors associated with high levels of sitting time and low levels of
      physical activity. With the advent and increasing availability of indoor tracking
      systems it is now becoming possible to build detailed pictures of the usage of
      indoor spaces. This paper reports initial results of indoor tracking used in
      conjunction with the ActivPAL activity monitoring device. In this paper we give
      an overview of the usage of the tracking system and its installation and
      illustrate some of the resultant data. We also provide preliminary results that
      investigate the relationship between location, light physical activity and
      sitting in a small sample of office workers (n=33) from two separate office
      environments in order to demonstrate the relevance and explanatory power of the
      technique. 

PMID- 25993516
TI  - Fluorescence characteristics and lifetime images of photosensitizers of
      talaporfin sodium and sodium pheophorbide a in normal and cancer cells.
AB  - Fluorescence spectra and fluorescence lifetime images of talaporfin sodium and
      sodium-pheophorbide a, which can be regarded as photosensitizers for photodynamic
      therapy, were measured in normal and cancer cells. The reduction of the
      fluorescence intensity by photoirradiation was observed for both photosensitizers
      in both cells, but the quenching rate was much faster in cancer cells than in
      normal cells. These results are explained in terms of the excessive generation of
      reactive oxygen species via photoexcitation of these photosensitizers in cancer
      cells. The fluorescence lifetimes of both photosensitizers in cancer cells are
      different from those in normal cells, which originates from the different
      intracellular environments around the photosensitizers between normal and cancer
      cells. 

PMID- 25993517
TI  - A Colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) Detection Platform for a
      Point-of-Care Dengue Detection System on a Lab-on-Compact-Disc.
AB  - The enzyme-linked Immunosorbent Assay (ELISA) is the gold standard clinical
      diagnostic tool for the detection and quantification of protein biomarkers.
      However, conventional ELISA tests have drawbacks in their requirement of time,
      expensive equipment and expertise for operation. Hence, for the purpose of rapid,
      high throughput screening and point-of-care diagnosis, researchers are
      miniaturizing sandwich ELISA procedures on Lab-on-a-Chip and Lab-on-Compact Disc
      (LOCD) platforms. This paper presents a novel integrated device to detect and
      interpret the ELISA test results on a LOCD platform. The system applies
      absorption spectrophotometry to measure the absorbance (optical density) of the
      sample using a monochromatic light source and optical sensor. The device performs
      automated analysis of the results and presents absorbance values and diagnostic
      test results via a graphical display or via Bluetooth to a smartphone platform
      which also acts as controller of the device. The efficacy of the device was
      evaluated by performing dengue antibody IgG ELISA on 64 hospitalized patients
      suspected of dengue. The results demonstrate high accuracy of the device, with
      95% sensitivity and 100% specificity in detection when compared with gold
      standard commercial ELISA microplate readers. This sensor platform represents a
      significant step towards establishing ELISA as a rapid, inexpensive and automatic
      testing method for the purpose of point-of-care-testing (POCT) in resource
      limited settings. 

PMID- 25993518
TI  - Design of an Embedded CMOS Temperature Sensor for Passive RFID Tag Chips.
AB  - This paper presents an ultra-low embedded power temperature sensor for passive
      RFID tags. The temperature sensor converts the temperature variation to a PTAT
      current, which is then transformed into a temperature-controlled frequency. A
      phase locked loop (PLL)-based sensor interface is employed to directly convert
      this temperature-controlled frequency into a corresponding digital output without
      an external reference clock. The fabricated sensor occupies an area of 0.021 mm2
      using the TSMC 0.18 1P6M mixed-signal CMOS process. Measurement results of the
      embedded sensor within the tag system shows a 92 nW power dissipation under 1.0 V
      supply voltage at room temperature, with a sensing resolution of 0.15  degrees
      C/LSB and a sensing accuracy of -0.7/0.6  degrees C from -30  degrees C to 70 
      degrees C after 1-point calibration at 30  degrees C. 

PMID- 25993519
TI  - A Wireless LC Sensor Coated with Ba0.9Bi0.066TiO3 for Measuring Temperature.
AB  - This paper presents a passive LC wireless sensor for measuring temperature. The
      sensor is designed as a parallel connection of a spiral inductor and an
      interdigitated capacitor and it was fabricated in a conductive layer using LTCC
      (Low Temperature Co-fired Ceramic) technology. The inderdigitated capacitor
      electrodes were coated with a thin film of bismuth doped barium titanate
      (Ba0.9Bi0.066TiO3), whose permittivity changes with temperature, which directly
      induces changes in the capacitance of the interdigitated capacitor and
      consequently changes the resonant frequency of the sensor. The measurements of S
      parameter of the sensor were performed using a Vector Network Analyzer (E5071B,
      Agilent Technologies, Santa Clara, CA, USA), whose port was connected to the
      antenna coil that was placed around the sensor in order to be able to wirelessly
      detect temperature, in the temperature range from 25  degrees C to 165  degrees
      C. 

PMID- 25993520
TI  - Seasonal Ecology and Behavior of an Endangered Rainforest Frog (Litoria rheocola)
      Threatened by Disease.
AB  - One of the most devastating wildlife diseases ever recorded is chytridiomycosis,
      a recently emerged amphibian disease that is caused by the chytrid fungus
      Batrachochytrium dendrobatidis. Understanding, predicting, and managing the
      impacts of chytridiomycosis on any amphibian species will require detailed
      information on its ecology and behavior because this pathogen is transmitted by
      contact with water or other individuals, and pathogen growth rates are thermally
      sensitive. The common mistfrog (Litoria rheocola) is an endangered tropical
      rainforest frog that has declined due to chytridiomycosis. We tracked L. rheocola
      during the winter (cool/dry) and summer (warm/wet) seasons at a low- and high
      elevation site. We found that seasonal differences in environmental temperatures
      and frog behavior should render this species most vulnerable to B. dendrobatidis
      during cooler months and at higher elevations, which matches observed patterns of
      infection prevalence in this species. During winter, frogs moved shorter
      distances than during summer, and they spent less time in vegetation and more
      time in the stream, which should increase exposure to aquatic B. dendrobatidis
      zoospores. At a low-elevation site (40 m ASL), estimated body temperatures were
      within the optimal range for B. dendrobatidis growth (15-25  degrees C) most of
      the time during winter, but they reached temperatures above this threshold
      frequently in summer. At a higher elevation (750 m ASL), estimated body
      temperatures were within the range most favorable for B. dendrobatidis year
      round, and did not exceed 25  degrees C, even during summer. Our study provides
      the first detailed information on the ecology and behavior of L. rheocola and
      suggests ecological mechanisms for infection dynamics that have been observed in
      this endangered species.

PMID- 25993521
TI  - How do living arrangements and intergenerational support matter for psychological
      health of elderly parents? Evidence from Myanmar, Vietnam, and Thailand.
AB  - Living arrangements and family support for older persons have become an
      increasingly important policy concern in developing and rapidly aging Asia.
      Formulating a sound elderly care policy for the region will benefit from
      empirically examining how living arrangements, particularly coresidence, and
      intergenerational exchanges of financial, instrumental, and emotional support are
      associated with old-age psychological health. This study analyzes data from
      nationally representative aging surveys in Myanmar, Vietnam, and Thailand for
      2011-2012 to offer a comparative perspective from Southeast Asia where various
      kinship systems coexist. Results suggest that coresidence with a child of
      culturally preferred gender significantly improves the emotional health of
      Vietnamese and Thai elders but with different implications. In Vietnam, living
      with a married son is more beneficial to parents' psychological wellbeing than
      living with other children. In Thailand, coresidence regardless of the child's
      gender improves old-age psychological wellbeing but living with a daughter brings
      greater benefits than living only with son. Evidence points to the importance of
      understanding the dominant kinship system that may shape normative filial
      expectations and gender role expectations within the family. In Vietnam and
      Thailand, the positive association holds even after intergenerational support is
      controlled, suggesting that the value of culturally preferred coresidence goes
      beyond practical functions. In Myanmar, there are almost no significant
      differences in psychological wellbeing among elderly across various living
      arrangements, except between coresidence and network living arrangements. For all
      settings, we do not find evidence in support of network family arrangements as a
      complete substitute for coresidence in terms of promoting old-age psychological
      wellbeing after filial support is controlled. Our study highlights important
      cultural nuances for theorizing the nature of the relationship between living
      arrangements and old-age psychological health, and presents the important need
      for more rigorous investigation of the causal links between these two phenomena
      in future research. 

PMID- 25993522
TI  - Does who you know in the positional hierarchy protect or hurt? Social capital,
      comparative reference group, and depression in two societies.
AB  - Does the socioeconomic status (SES) that one's (ego's) network members (alters)
      occupy indicate social resources or social comparison standards in the dynamics
      of health across culture? Using nationally representative data simultaneously
      collected from the United States and urban China, this study examines two
      competing theories-social capital and comparative reference group-in the two
      societies and compares their different application across the two societies using
      two cultural explanations, relational dependence and self-evaluation motive.
      Social capital theory expects absolute accessed SES and the size of higher
      accessed socioeconomic positions to protect health, and the size of lower
      accessed socioeconomic positions to harm health. But comparative reference group
      theory predicts the opposite. Additionally, the relational dependence explanation
      anticipates social capital theory to be more applicable to urban China and
      comparative reference group theory to be more applicable to the United States.
      The self-evaluation motive explanation expects the same pattern across the two
      societies in the examination of the size of lower accessed socioeconomic
      positions but the opposite pattern in the analysis of absolute accessed SES and
      the size of higher accessed socioeconomic positions. This study focuses on
      depressive symptoms and measures accessed occupational status. Results are
      consistent with the self-evaluation motive explanation. They support both social
      capital theory and comparative reference group theory in the United States but
      only the latter theory in urban China. 

PMID- 25993523
TI  - Evidence for a Putative Circadian Kiss-Clock in the Hypothalamic AVPV in Female
      Mice.
AB  - The kisspeptin (Kp) neurons in the anteroventral periventricular nucleus (AVPV)
      are essential for the preovulatory LH surge, which is gated by circulating
      estradiol (E2) and the time of day. We investigated whether AVPV Kp neurons in
      intact female mice may be the site in which both E2 and daily signals are
      integrated and whether these neurons may host a circadian oscillator involved in
      the timed LH surge. In the afternoon of proestrous day, Kp immunoreactivity
      displayed a marked and transient decrease 2 hours before the LH surge. In
      contrast, Kp content was stable throughout the day of diestrus, when LH levels
      are constantly low. AVPV Kp neurons expressed the clock protein period 1 (PER1)
      with a daily rhythm that is phase delayed compared with the PER1 rhythm measured
      in the main clock of the suprachiasmatic nuclei (SCN). PER1 rhythm in the AVPV,
      but not in the SCN, exhibited a significant phase delay of 2.8 hours in diestrus
      as compared with proestrus. Isolated Kp-expressing AVPV explants from
      PER2::LUCIFERASE mice displayed sustained circadian oscillations of
      bioluminescence with a circadian period (23.2 h) significantly shorter than that
      of SCN explants (24.5 h). Furthermore, in AVPV explants incubated with E2 (10 nM
      to 1 MUM), the circadian period was lengthened by 1 hour, whereas the SCN clock
      remained unaltered. In conclusion, these findings indicate that AVPV Kp neurons
      display an E2-dependent daily rhythm, which may possibly be driven by an
      intrinsic circadian clock acting in combination with the SCN timing signal. 

PMID- 25993524
TI  - Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not
      Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle
      Activation in Females Followed by Sexual Reversal to Males.
AB  - Gonadotropins are primary hormones that control vertebrate reproduction. In a
      recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by
      disrupting FSH and LH-beta genes (fshb and lhb) using transcription activator
      like effector nuclease (TALEN) technology. Using the same approach, we
      successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present
      study. In contrast to the deficiency of its cognate ligand FSH, the fshr
      deficient females showed a complete failure of follicle activation with all
      ovarian follicles arrested at the primary growth-previtellogenic transition,
      which is the marker for puberty onset in females. Interestingly, after blockade
      at the primary growth stage for varying times, all females reversed to males, and
      all these males were fertile. In fshr-deficient males, spermatogenesis was normal
      in adults, but the initiation of spermatogenesis in juveniles was retarded. In
      contrast to fshr, the deletion of the lhcgr gene alone caused no obvious
      phenotypes in both males and females; however, double mutation of fshr and lhcgr
      resulted in infertile males. In summary, our results in the present study showed
      that Fshr was indispensable to folliculogenesis and the disruption of the fshr
      gene resulted in a complete failure of follicle activation followed by
      masculinization into males. In contrast, lhcgr does not seem to be essential to
      zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr
      deficiency could phenocopy the deficiency of their cognate ligands FSH and LH,
      which is likely due to the fact that Fshr can be activated by both FSH and LH in
      the zebrafish. 

PMID- 25993525
TI  - Hypothalamic Prolactin Regulation of Luteinizing Hormone Secretion in the Female
      Rat.
AB  - Prolactin (PRL) levels increase in response to long-term antipsychotic treatment
      that disrupts reproductive function. Recent evidence suggests that activation of
      central PRL receptors (PRLR) inhibits LH secretion and in ovariectomized rats.
      However, the mechanisms involved, the mode of LH secretion affected and relevance
      to hyperprolactinemia remain unknown. We therefore investigated the contribution
      of central PRL/PRLR signaling to the control of estradiol-induced surges of LH
      and PRL and pulsatile LH secretion under basal and hyperprolactinemic conditions.
      First, by subjecting ovariectomized estradiol-primed rats
      intracerebroventricularly administered with PRL to frequent blood sampling, we
      demonstrated that acute activation of hypothalamic PRLR disrupts pulsatile LH
      secretion. Pretreatment (intracerebroventricularly) with the pure PRLR
      antagonist, Delta1-9-G129R-hPRL, or the gamma-aminobutyric acid receptor type A
      antagonist, bicuculline, blocked this effect. Next, we revealed that sustained
      blockade of hypothalamic PRLR using Delta1-9-G129R-hPRL augmented the magnitude
      of LH surges induced by estradiol benzoate and progesterone treatment and
      suppressed the concomitant surges of PRL. Finally, we determined that acute
      antagonism of central PRLR is insufficient to normalize the duration of the LH
      pulse interval prolonged as a result of hyperprolactinemia induced by chronic
      exposure to the atypical antipsychotic sulpiride. These data serve as the first
      evidence to suggest that PRL signaling through hypothalamic PRLR inhibits
      pulsatile secretion of LH in a gamma-aminobutyric acid receptor type A-dependent
      fashion and tonically restrains the magnitude of the LH surge. Furthermore, our
      results indicate that transient blockade of hypothalamic PRL/PRLR signaling is
      not an effective strategy for restoring LH pulsatility perturbed by chronic
      hyperprolactinemia. 

PMID- 25993526
TI  - Preweaning GH Treatment Normalizes Body Growth Trajectory and Reverses Metabolic
      Dysregulation in Adult Offspring After Maternal Undernutrition.
AB  - Maternal undernutrition (UN) results in growth disorders and metabolic
      dysfunction in offspring. Although dysregulation of the GH-IGF axis in offspring
      is a known consequence of maternal UN, little is known about the efficacy of GH
      treatment during the period of developmental plasticity on later growth and
      metabolic outcomes. The present study investigated the effect of preweaning GH
      treatment on growth, glucose metabolism, and the GH-IGF axis in adult male and
      female offspring after maternal UN. Female Sprague Dawley rats were fed either a
      chow diet ad libitum (control [CON]) or 50% of ad libitum (UN) throughout
      pregnancy. From postnatal day 3, CON and UN pups received either saline (CON-S
      and UN-S) or GH (2.5 MUg/g.d CON-GH and UN-GH) daily throughout lactation. At
      weaning, male and female offspring were randomly selected from each litter and
      fed a standard chow diet for the remainder of the study. Preweaning GH treatment
      normalized maternal UN-induced alterations in postweaning growth trajectory and
      concomitant adiposity in offspring. Plasma leptin concentrations were increased
      in UN-S offspring and normalized in the UN-GH group. Hepatic GH receptor
      expression was significantly elevated in UN-S offspring and normalized with GH
      treatment. Hepatic IGF binding protein-2 gene expression and plasma IGF-1 to IGF
      binding protein-3 ratio was reduced in UN-S offspring and elevated with GH
      treatment. GH treatment during a critical developmental window prevented maternal
      UN-induced changes in postnatal growth patterns and related adiposity, suggesting
      that manipulation of the GH-IGF-1 axis in early development may represent a
      promising avenue to prevent adverse developmental programming effects in
      adulthood. 

PMID- 25993527
TI  - Recombinant Nepenthesin II for Hydrogen/Deuterium Exchange Mass Spectrometry.
AB  - The pitcher secretions of the Nepenthes genus of carnivorous plants contain a
      proteolytic activity that is very useful for hydrogen/deuterium exchange mass
      spectrometry (HX-MS). Our efforts to reconstitute pitcher fluid activity using
      recombinant nepenthesin I (one of two known aspartic proteases in the fluid)
      revealed a partial cleavage profile and reduced enzymatic stability in certain HX
      MS applications. We produced and characterized recombinant nepenthesin II to
      determine if it complemented nepenthesin I in HX-MS applications. Nepenthesin II
      shares many properties with nepenthesin I, such as fast digestion at reduced
      temperature and pH, and broad cleavage specificity, but in addition, it cleaves C
      terminal to tryptophan. Neither enzyme reproduces the C-terminal proline cleavage
      we observed in the natural extract. Nepenthesin II is considerably more resistant
      to chemical denaturants and reducing agents than nepenthesin I, and it possesses
      a stability profile that is similar to that of pepsin. Higher stability combined
      with the slightly broader cleavage specificity makes nepenthesin II a useful
      alternative to pepsin and a more complete replacement for pitcher fluid in HX-MS
      applications. 

PMID- 25993528
TI  - Importance of both fatness and aerobic fitness on metabolic syndrome risk in
      Japanese children.
AB  - Associations between body mass index (BMI), peak oxygen consumption (VO(2peak)),
      and metabolic syndrome (MetS) risk factors have not been adequately studied in
      Japanese children. Here the relationships between these parameters and the
      threshold aerobic fitness level necessary for low MetS risk were determined. The
      participants (299 children; 140 boys and 159 girls, aged 9.1 +/- 0.3 years) were
      divided into four groups using the medians of predicted VO(2peak) (pVO(2peak))
      and BMI. MetS risk scores were calculated using z-scores. Receiver Operating
      Characteristic analysis was used to determine the threshold aerobic fitness level
      necessary for low MetS risk. The MetS risk score of the High BMI group was
      significantly higher than that of the Low BMI group for both sexes (p < 0.0001).
      However, the High BMI/High Fitness group had a significantly lower MetS risk
      score than the High BMI/Low Fitness group for both sexes. The (p)VO(2peak )cut
      off values for low MetS risk were 47.9 and 44.9 ml/kg/min for boys and girls,
      respectively. Our results suggest that improvements in both fatness and aerobic
      fitness are important for decreasing MetS risk. We also confirmed the
      (p)VO(2peak) of cut-off values necessary for low MetS risk in Japanese children.

PMID- 25993530
TI  - Ageing and feature binding in visual working memory: The role of presentation
      time.
AB  - A large body of research has clearly demonstrated that healthy ageing is
      accompanied by an associative memory deficit. Older adults exhibit
      disproportionately poor performance on memory tasks requiring the retention of
      associations between items (e.g., pairs of unrelated words). In contrast to this
      robust deficit, older adults' ability to form and temporarily hold bound
      representations of an object's surface features, such as colour and shape,
      appears to be relatively well preserved. However, the findings of one set of
      experiments suggest that older adults may struggle to form temporary bound
      representations in visual working memory when given more time to study objects.
      However, these findings were based on between-participant comparisons across
      experimental paradigms. The present study directly assesses the role of
      presentation time in the ability of younger and older adults to bind shape and
      colour in visual working memory using a within-participant design. We report new
      evidence that giving older adults longer to study memory objects does not
      differentially affect their immediate memory for feature combinations relative to
      individual features. This is in line with a growing body of research suggesting
      that there is no age-related impairment in immediate memory for colour-shape
      binding. 

PMID- 25993529
TI  - Mitochondrial DNA haplogroups and short-term neurological outcomes of ischemic
      stroke.
AB  - Stroke is one of the leading causes of death and long-term disability worldwide.
      Mitochondrial DNA (mtDNA) is a potential contributor for the sex differences of
      ischemic stroke heritability. Although mtDNA haplogroups were associated with
      stroke onset, their impacts on stroke outcomes remain unclear. This study aimed
      to evaluate the impacts of mtDNA haplogroups on short-term outcomes of
      neurological functions in patients with ischemic stroke. A total of 303 patients
      were included, and their clinical data and mtDNA sequences were analyzed. Based
      on the changes between baseline and 14-day follow-up stroke severity, our results
      showed that haplogroup N9 was an independent protective factor against
      neurological worsening in acute ischemic stroke patients. These findings
      supported that mtDNA variants play a role in post-stroke neurological recovery,
      thus providing evidences for future pharmacological intervention in mitochondrial
      function. 

PMID- 25993531
TI  - A bimetallic iridium(ii) catalyst: [{Ir(IDipp)(H)}2][BF4]2 (IDipp = 1,3-bis(2,6
      diisopropylphenylimidazol-2-ylidene)).
AB  - A new Ir(ii) complex [{Ir(MU-kappaCNHC,eta(6)Dipp-IDipp)(H)}2][BF4]2 has been
      prepared and fully characterised. This complex acts as a catalyst for the
      hydroalkynylation of imines according to an unprecedented diiridium-mediated
      mechanism. 

PMID- 25993532
TI  - Using Hierarchical Virtual Screening To Combat Drug Resistance of the HIV-1
      Protease.
AB  - Human immunodeficiency virus (HIV) protease inhibitors (PIs) are important
      components of highly active anti-retroviral therapy (HAART) that block the
      catalytic site of HIV protease, thus preventing maturation of the HIV virion.
      However, with two decades of PI prescriptions in clinical practice, drug
      resistant HIV mutants have now been found for all of the PI drugs. Therefore, the
      continuous development of new PI drugs is crucial both to combat the existing
      drug-resistant HIV strains and to provide treatments for future patients. Here we
      purpose an HIV PI drug design strategy to select candidate PIs with binding
      energy distributions dominated by interactions with conserved protease residues
      in both wild-type and various drug-resistant mutants. On the basis of this
      strategy, we have constructed a virtual screening pipeline including
      combinatorial library construction, combinatorial docking, MM/GBSA-based
      rescoring, and reranking on the basis of the binding energy distribution. We have
      tested our strategy on lopinavir by modifying its two functional groups. From an
      initial 751 689 candidate molecules, 18 candidate inhibitors were selected using
      the pipeline for experimental validation. IC50 measurements and drug resistance
      predictions successfully identified two ligands with both HIV protease inhibitor
      activity and an improved drug resistance profile on 2382 HIV mutants. This study
      provides a proof of concept for the integration of MM/GBSA energy analysis and
      drug resistance information at the stage of virtual screening and sheds light on
      future HIV drug design and the use of virtual screening to combat drug
      resistance. 

PMID- 25993533
TI  - A robust ordering strategy for retailers facing a free shipping option.
AB  - Free shipping with conditions has become one of the most effective marketing
      tools available. An increasing number of companies, especially e-businesses,
      prefer to offer free shipping with some predetermined condition, such as a
      minimum purchase amount by the customer. However, in practice, the demands of
      buyers are uncertain; they are often affected by many factors, such as the
      weather and season. We begin by modeling the centralized ordering problem in
      which the supplier offers a free shipping service and retailers face stochastic
      demands. As these random data are considered, only partial information such as
      the known mean, support, and deviation is needed. The model is then analyzed via
      a robust optimization method, and the two types of equivalent sets of uncertainty
      constraints that are obtained provide good mathematical properties with
      consideration of the robustness of solutions. Subsequently, a numerical example
      is used to compare the results achieved from a robust optimization method and the
      linear decision rules. Additionally, the robustness of the optimal solution is
      discussed, as it is affected by the minimum quantity parameters. The increasing
      cost-threshold relationship is divided into three periods. In addition, the case
      study shows that the proposed method achieves better stability as well as
      computational complexity. 

PMID- 25993534
TI  - A novel tool to mitigate by-catch mortality of baltic seals in coastal fyke net
      fishery.
AB  - Developing methods to reduce the incidental catch of non-target species is
      important, as by-catch mortality poses threats especially to large aquatic
      predators. We examined the effectiveness of a novel device, a "seal sock", in
      mitigating the by-catch mortality of seals in coastal fyke net fisheries in the
      Baltic Sea. The seal sock developed and tested in this study was a cylindrical
      net attached to the fyke net, allowing the seals access to the surface to breathe
      while trapped inside fishing gear. The number of dead and live seals caught in
      fyke nets without a seal sock (years 2008-2010) and with a sock (years 2011-2013)
      was recorded. The seals caught in fyke nets were mainly juveniles. Of ringed
      seals (Phoca hispida botnica) both sexes were equally represented, while of grey
      seals (Halichoerus grypus) the ratio was biased (71%) towards males. All the by
      caught seals were dead in the fyke nets without a seal sock, whereas 70% of
      ringed seals and 11% of grey seals survived when the seal sock was used. The seal
      sock proved to be effective in reducing the by-catch mortality of ringed seals,
      but did not perform as well with grey seals. 

PMID- 25993535
TI  - In vivo Tracking of Dendritic Cell using MRI Reporter Gene, Ferritin.
AB  - The noninvasive imaging of dendritic cells (DCs) migrated into lymph nodes (LNs)
      can provide helpful information on designing DCs-based immunotherapeutic
      strategies. This study is to investigate the influence of transduction of human
      ferritin heavy chain (FTH) and green fluorescence protein (GFP) genes on inherent
      properties of DCs, and the feasibility of FTH as a magnetic resonance imaging
      (MRI) reporter gene to track DCs migration into LNs. FTH-DCs were established by
      the introduction of FTH and GFP genes into the DC cell line (DC2.4) using
      lentivirus. The changes in the rate of MRI signal decay (R2*) resulting from FTH
      transduction were analyzed in cell phantoms as well as popliteal LN of mice after
      subcutaneous injection of those cells into hind limb foot pad by using a multiple
      gradient echo sequence on a 9.4 T MR scanner. The transduction of FTH and GFP did
      not influence the proliferation and migration abilities of DCs. The expression of
      co-stimulatory molecules (CD40, CD80 and CD86) in FTH-DCs was similar to that of
      DCs. FTH-DCs exhibited increased iron storage capacity, and displayed a
      significantly higher transverse relaxation rate (R2*) as compared to DCs in
      phantom. LNs with FTH-DCs exhibited negative contrast, leading to a high R2* in
      both in vivo and ex vivo T2*-weighted images compared to DCs. On histological
      analysis FTH-DCs migrated to the subcapsular sinus and the T cell zone of LN,
      where they highly expressed CD25 to bind and stimulate T cells. Our study
      addresses the feasibility of FTH as an MRI reporter gene to track DCs migration
      into LNs without alteration of their inherent properties. This study suggests
      that FTH-based MRI could be a useful technique to longitudinally monitor DCs and
      evaluate the therapeutic efficacy of DC-based vaccines. 

PMID- 25993536
TI  - Immunostaining to visualize murine enteric nervous system development.
AB  - The enteric nervous system is formed by neural crest cells that proliferate,
      migrate and colonize the gut. Following colonization, neural crest cells must
      then differentiate into neurons with markers specific for their neurotransmitter
      phenotype. Cholinergic neurons, a major neurotransmitter phenotype in the enteric
      nervous system, are identified by staining for choline acetyltransferase (ChAT),
      the synthesizing enzyme for acetylcholine. Historical efforts to visualize
      cholinergic neurons have been hampered by antibodies with differing specificities
      to central nervous system versus peripheral nervous system ChAT. We and others
      have overcome this limitation by using an antibody against placental ChAT, which
      recognizes both central and peripheral ChAT, to successfully visualize embryonic
      enteric cholinergic neurons. Additionally, we have compared this antibody to
      genetic reporters for ChAT and shown that the antibody is more reliable during
      embryogenesis. This protocol describes a technique for dissecting, fixing and
      immunostaining of the murine embryonic gastrointestinal tract to visualize
      enteric nervous system neurotransmitter expression. 

PMID- 25993538
TI  - Carriage and Genetic Diversity of Methicillin-Resistant Staphylococcus aureus
      among Patients and Healthcare Workers in a Serbian University Hospital.
AB  - OBJECTIVES: There is a paucity of data on methicillin-resistant Staphylococcus
      aureus (MRSA) epidemiology among Balkan countries. The aim of our study was to
      determine the prevalence of nasal and pharyngeal carriages and diversity of MRSA
      among patients and healthcare workers (HCWs) in the major referral centre in
      Serbia, and to evaluate performance of three different media for MRSA screening.
      METHODS: Nasal and pharyngeal swabs were obtained from 195 patients and 105 HCWs
      in Emergency Department (ED), Surgical Department (SD) and Medical Department
      (MD). After broth enrichment, samples were inoculated onto MRSA-ID, ORSA and
      oxacillin-MSA and incubated for 24/48 hours. Characterisation of isolated MRSA
      strains was determined by MLVA, spa, SCCmec and agr typing, PVL genes detection
      and antimicrobial susceptibility. RESULTS: MRSA carriage prevalence was 11.8% in
      patients and 7.6% in HCWs. Introduction of pharyngeal swabs in screening
      procedure increased MRSA carriage rate by over 30%. Variable found to be
      independently associated with an increased risk for MRSA carriage was ED (odd
      ratio (OR) = 4.45, 95% confidence interval (CI) 1.78-11.14). A higher risk of
      multidrug-resistant MRSA carriage was observed among patients (OR = 22; 95% CI
      1.92-251.54). CC5-MRSA-SCCmecI was the dominant clone among patients and HCWs in
      ED and MD, while high genetic diversity of community-associated MRSA (CA-MRSA)
      was shown in SD especially among HCWs. MRSA-ID was superior to the other tested
      media with a sensitivity/specificity of 95.2% and 99.6% after 48 hours of
      incubation. CONCLUSIONS: These results indicate high MRSA carriage rate in the
      hospital and emergence of CA-MRSA through HCWs in these settings. MRSA-ID was the
      optimal available choice for MRSA screening.

PMID- 25993539
TI  - Tree foliar chemistry in an African savanna and its relation to life history
      strategies and environmental filters.
AB  - Understanding the relative importance of environment and life history strategies
      in determining leaf chemical traits remains a key objective of plant ecology. We
      assessed 20 foliar chemical properties among 12 African savanna woody plant
      species and their relation to environmental variables (hillslope position,
      precipitation, geology) and two functional traits (thorn type and seed dispersal
      mechanism). We found that combinations of six leaf chemical traits (lignin, hemi
      cellulose, zinc, boron, magnesium, and manganese) predicted the species with 91%
      accuracy. Hillslope position, precipitation, and geology accounted for only 12%
      of the total variance in these six chemical traits. However, thorn type and seed
      dispersal mechanism accounted for 46% of variance in these chemical traits. The
      physically defended species had the highest concentrations of hemi-cellulose and
      boron. Species without physical defense had the highest lignin content if
      dispersed by vertebrates, but threefold lower lignin content if dispersed by
      wind. One of the most abundant woody species in southern Africa, Colophospermum
      mopane, was found to have the highest foliar concentrations of zinc, phosphorus,
      and delta(13)C, suggesting that zinc chelation may be used by this species to
      bind metallic toxins and increase uptake of soil phosphorus. Across all studied
      species, taxonomy and physical traits accounted for the majority of variability
      in leaf chemistry.

PMID- 25993540
TI  - Free convection in a parallelogrammic porous cavity filled with a nanofluid using
      Tiwari and Das' nanofluid model.
AB  - The free convection heat transfer of Cu-water nanofluids in a parallelogrammic
      enclosure filled with porous media is numerically analyzed. The bottom and top of
      the enclosure are insulated while the sidewalls are subject to limited
      temperature difference. The Darcy flow and the Tiwari and Das' nanofluid models
      are considered. The governing dimensionless partial differential equations are
      numerically solved using a finite difference code. The results are reported for
      isotherms and streamlines as well as Nusselt number as a function of the volume
      fraction of nanoparticles, porosity, types of the porous matrix, inclination
      angle, aspect ratio and different Rayleigh numbers. It is found that the presence
      of the nanoparticles inside the enclosure deteriorates the heat transfer rate,
      which is caused due to the increase of dynamic viscosity by the presence of
      nanoparticles. Therefore, in applications in which the nanofluids are used for
      their advantages, such as enhanced dielectric properties or antibacterial
      properties, more caution for the heat transfer design of the enclosure is
      necessary. 

PMID- 25993541
TI  - Overexpression of RLIP76 Required for Proliferation in Meningioma Is Associated
      with Recurrence.
AB  - The GTPase-activating protein RLIP76 is overexpressed in and correlates with the
      pathological grade of many malignant tumor cells. But the potential correlation
      between RLIP76 and clinical outcomes in patients with meningioma remains unknown.
      In this study, we examined the expression of RLIP76 in meningioma and correlated
      the RLIP76 expression to the patient outcome. RLIP76 expression in tumor tissues
      was examined with immunohistochemistry, quantitative reverse-transcription
      polymerase chain reaction(RT-PCR) and Western-blot. Immunohistochemistry showed
      an increased RLIP76 immunostaining score in anaplastic and atypical meningiomas
      versus classical meningiomas. Statistical analyses revealed that RLIP76
      immunostaining positively correlated with immunostaining for Ki-67, a nuclear
      protein highly expressed in proliferating cells(r=0.29, p=0.034 by Spearman's
      correlation coefficient). Clinicopathological evaluation suggested that RLIP76
      expression be associated with tumor grade and recurrence(P<0.05). Univariate and
      Cox analysis indicated that RLIP76 was an independent prognostic factor for tumor
      recurrence. Furthermore, the human malignant meningioma cell lines IOMM-Lee and
      CH157-MN stably transfected with short hairpin RNA (siRNA) targeting RLIP76 were
      then examined by in vitro growth assays, and apoptosis assays. RLIP76 knockdown
      in IOMM-Lee and CH157-MN cells inhibited cell proliferation and induced
      apoptosis. Western blot analysis revealed that cells underexpressing RLIP76
      exhibited decreased B-cell lymphoma-2(Bcl-2) expression but increased apoptosis
      effector caspase-3 expression. These findings demonstrate that high RLIP76
      expression is associated with a poor outcome of meningioma and may provide a new
      gene therapy approach for patients with malignant meningiomas. 

PMID- 25993542
TI  - Y fuse? Sex chromosome fusions in fishes and reptiles.
AB  - Chromosomal fusion plays a recurring role in the evolution of adaptations and
      reproductive isolation among species, yet little is known of the evolutionary
      drivers of chromosomal fusions. Because sex chromosomes (X and Y in male
      heterogametic systems, Z and W in female heterogametic systems) differ in their
      selective, mutational, and demographic environments, those differences provide a
      unique opportunity to dissect the evolutionary forces that drive chromosomal
      fusions. We estimate the rate at which fusions between sex chromosomes and
      autosomes become established across the phylogenies of both fishes and squamate
      reptiles. Both the incidence among extant species and the establishment rate of Y
      autosome fusions is much higher than for X-autosome, Z-autosome, or W-autosome
      fusions. Using population genetic models, we show that this pattern cannot be
      reconciled with many standard explanations for the spread of fusions. In
      particular, direct selection acting on fusions or sexually antagonistic selection
      cannot, on their own, account for the predominance of Y-autosome fusions. The
      most plausible explanation for the observed data seems to be (a) that fusions are
      slightly deleterious, and (b) that the mutation rate is male-biased or the
      reproductive sex ratio is female-biased. We identify other combinations of
      evolutionary forces that might in principle account for the data although they
      appear less likely. Our results shed light on the processes that drive structural
      changes throughout the genome. 

PMID- 25993543
TI  - Intramolecular hydrogen bonds involving organic fluorine in the derivatives of
      hydrazides: an NMR investigation substantiated by DFT based theoretical
      calculations.
AB  - The rare examples of intramolecular hydrogen bonds (HB) of the type the N-H???F
      C, detected in a low polarity solvent in the derivatives of hydrazides, by
      utilizing one and two-dimensional solution state multinuclear NMR techniques, are
      reported. The observation of through-space couplings, such as, (1h)JFH, and
      (1h)JFN, provides direct evidence for the existence of intra-molecular HB.
      Solvent induced perturbations and the variable temperature NMR experiments
      unambiguously establish the presence of intramolecular HB. The existence of
      multiple conformers in some of the investigated molecules is also revealed by two
      dimensional HOESY and (15)N-(1)H HSQC experiments. The (1)H DOSY experimental
      results discard any possibility of self or cross dimerization of the molecules.
      The derived NMR experimental results are further substantiated by Density
      Function Theory (DFT) based Non Covalent Interaction (NCI), and Quantum Theory of
      Atom in Molecule (QTAIM) calculations. The NCI calculations served as a very
      sensitive tool for detection of non-covalent interactions and also confirm the
      presence of bifurcated HBs.

PMID- 25993544
TI  - Surgical Missions: A View From Yet Another Side.

PMID- 25993545
TI  - Left Ventricular Diastolic Dysfunction Assessment with Dual-Source CT.
AB  - PURPOSE: To assess the impact of left ventricular (LV) diastolic dysfunction on
      left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to
      find a viable alternative prognostic parameter of CT for LV diastolic dysfunction
      through quantitative evaluation of LA phasic volume and function in patients with
      LV diastolic dysfunction. MATERIALS AND METHODS: Seventy-seven patients were
      examined using DSCT and Doppler echocardiography on the same day. Reservoir,
      conduit, and contractile function of LA were evaluated by measuring LA volume
      (LAV) during different cardiac phases and all parameters were normalized to body
      surface area (BSA). Patients were divided into four groups (normal, impaired
      relaxation, pseudonormal, and restrictive LV diastolic filling) according to
      echocardiographic findings. The LA phasic volume and function in different stages
      of LV diastolic function was compared using one-way ANOVA analysis. The
      correlations between indexed volume of LA (LAVi) and diastolic function in
      different stages of LV were evaluated using Spearman correlation analysis.
      RESULTS: LA ejection fraction (LAEF), LA contraction, reservoir, and conduit
      function in patients in impaired relaxation group were not different from those
      in the normal group, but they were lower in patients in the pseudonormal and
      restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function,
      there were no significant differences between the patients in the pseudonormal
      group and restrictive filling group (P = 0.195). There was a strong correlation
      between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001),
      minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at
      the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV
      diastolic function. The LAVi increased as the severity of LV diastolic
      dysfunction increased. CONCLUSIONS: LA remodeling takes place in patients with LV
      diastolic dysfunction. At the same time, LA phasic volume and function parameters
      evaluated by DSCT indicated the severity of the LV diastolic dysfunction.
      Quantitative analysis of LA phasic volume and function parameters using DSCT
      could be a viable alternative prognostic parameter of LV diastolic function.

PMID- 25993546
TI  - Specific changes in conduction velocity recovery cycles of single nociceptors in
      a patient with erythromelalgia with the I848T gain-of-function mutation of
      Nav1.7.
AB  - Seven patients diagnosed with erythromelalgia (EM) were investigated by
      microneurography to record from unmyelinated nerve fibers in the peroneal nerve.
      Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M),
      whereas no mutations of coding regions of Navs were found in 5 patients with EM.
      Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the
      patients with EM showed spontaneous activity. In the patient with mutation I848T,
      all nociceptors, but not sympathetic efferents, displayed enhanced early
      subnormal conduction in the velocity recovery cycles and the expected late
      subnormality was reversed to supranormal conduction. The larger hyperpolarizing
      shift of activation might explain the difference to the I228M mutation.
      Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the
      patient carrying the I848T mutation, confirming in human subjects that the
      presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant
      channels. The characteristic pattern of changes in conduction velocity observed
      in the patient with the I848T gain-of function mutation in Nav1.7 could be
      explained by axonal depolarization and concomitant inactivation of Nav1.7. If
      this were true, activity-dependent hyperpolarization would reverse inactivation
      of Nav1.7 and account for the supranormal CV. This mechanism might explain normal
      pain thresholds under resting conditions. 

PMID- 25993547
TI  - A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02
      (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to
      severe chronic low back pain treatment.
AB  - The objective of this multicenter, double-blind, placebo-controlled, randomized
      withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse
      deterrent formulation containing pellets of extended-release oxycodone
      hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo
      in the treatment of moderate-to-severe chronic low back pain. An open-label
      titration period in which all patients received ALO-02 was followed by a double
      blind treatment period where patients meeting treatment response criteria were
      randomized to either a fixed dose of ALO-02 or placebo. Daily average low back
      pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663
      patients screened, 410 received ALO-02 during the open-label conversion and
      titration period and 281 patients were randomized to the double-blind treatment
      period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score
      from randomization baseline to the final 2 weeks of the treatment period was
      significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty
      four percent of patients treated with placebo and 57.5% of patients treated with
      ALO-02 reported >=30% improvement in weekly average NRS-Pain scores from
      screening to the final 2 weeks of the treatment period (P = 0.0248). In the
      double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of
      patients in the placebo group experienced a treatment-emergent adverse event
      (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment
      period were nausea, vomiting, and constipation, consistent with opioid therapy.
      ALO-02 has been demonstrated to provide significant reduction of pain in patients
      with chronic low back pain and has a safety profile similar to other opioids.

PMID- 25993549
TI  - A multifaceted workplace intervention for low back pain in nurses' aides: a
      pragmatic stepped wedge cluster randomised controlled trial.
AB  - This study established the effectiveness of a workplace multifaceted intervention
      consisting of participatory ergonomics, physical training, and cognitive
      behavioural training (CBT) for low back pain (LBP). Between November 2012 and May
      2014, we conducted a pragmatic stepped wedge cluster randomised controlled trial
      with 594 workers from eldercare workplaces (nursing homes and home care)
      randomised to 4 successive time periods, 3 months apart. The intervention lasted
      12 weeks and consisted of 19 sessions in total (physical training [12 sessions],
      CBT [2 sessions], and participatory ergonomics [5 sessions]). Low back pain was
      the outcome and was measured as days, intensity (worst pain on a 0-10 numeric
      rank scale), and bothersomeness (days) by monthly text messages. Linear mixed
      models were used to estimate the intervention effect. Analyses were performed
      according to intention to treat, including all eligible randomised participants,
      and were adjusted for baseline values of the outcome. The linear mixed models
      yielded significant effects on LBP days of -0.8 (95% confidence interval [CI], 
      1.19 to -0.38), LBP intensity of -0.4 (95% CI, -0.60 to -0.26), and
      bothersomeness days of -0.5 (95% CI, -0.85 to -0.13) after the intervention
      compared with the control group. This study shows that a multifaceted
      intervention consisting of participatory ergonomics, physical training, and CBT
      can reduce LBP among workers in eldercare. Thus, multifaceted interventions may
      be relevant for improving LBP in a working population. 

PMID- 25993550
TI  - No pain, functional gain: the importance of pain management in older adults with
      cognitive impairment.

PMID- 25993548
TI  - Targeting cells of the myeloid lineage attenuates pain and disease progression in
      a prostate model of bone cancer.
AB  - Tumor cells frequently metastasize to bone where they can generate cancer-induced
      bone pain (CIBP) that can be difficult to fully control using available
      therapies. Here, we explored whether PLX3397, a high-affinity small molecular
      antagonist that binds to and inhibits phosphorylation of colony-stimulating
      factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine
      kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and
      function of a subset of the myeloid cells including macrophages, osteoclasts, and
      mast cells. Preliminary experiments show that PLX3397 attenuated inflammatory
      pain after formalin injection into the hind paw of the rat. As there is an
      inflammatory component in CIBP, involving macrophages and osteoclasts, the effect
      of PLX3397 was explored in a prostate model of CIBP where skeletal pain, cancer
      cell proliferation, tumor metastasis, and bone remodeling could be monitored in
      the same animal. Administration of PLX3397 was initiated on day 14 after prostate
      cancer cell injection when the tumor was well established, and tumor-induced bone
      remodeling was first evident. Over the next 6 weeks, sustained administration of
      PLX3397 attenuated CIBP behaviors by approximately 50% and was equally
      efficacious in reducing tumor cell growth, formation of new tumor colonies in
      bone, and pathological tumor-induced bone remodeling. Developing a better
      understanding of potential effects that analgesic therapies have on the tumor
      itself may allow the development of therapies that not only better control the
      pain but also positively impact disease progression and overall survival in
      patients with bone cancer. 

PMID- 25993551
TI  - Local anesthetics take a central action in analgesia.

PMID- 25993552
TI  - Molecular Psychiatry: Twenty years of progress from bench to clinic.

PMID- 25993553
TI  - Midbrain dopamine D2/D3 receptor availability and drug craving are associated
      with mesocorticolimbic gray matter volume in methamphetamine users.

PMID- 25993554
TI  - The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The
      Tromso Study.
AB  - BACKGROUND AND OBJECTIVE: In addition to its role as a transport protein, the
      vitamin D binding protein (DBP) may also affect lipid metabolism, inflammation
      and carcinogenesis. There are three common variants of the DBP, Gc1s (1s), Gc1f
      (1f), Gc2 (2) that result in six common phenotypes (1s/1s, 1s/1f, 1s/2, 1f/1f,
      1f/2, and 2/2). These phenotypes can be identified by genotyping for the two
      single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP
      variants have different binding coefficients for the vitamin D metabolites, and
      accordingly there may be important relations between DBP phenotypes and health.
      METHODS: DNA was prepared from subjects who participated in the fourth survey of
      the Tromso Study in 1994-1995 and who were registered with the endpoints
      myocardial infarction (MI), type 2 diabetes (T2DM), cancer or death as well as a
      randomly selected control group. The endpoint registers were complete up to 2010-
      2013. Genotyping was performed for rs7041 and rs4588 and serum 25-hydroxyvitamin
      D (25(OH)D) was measured. RESULTS: Genotyping for rs7041 and rs4588 was performed
      successfully in 11 704 subjects. Among these, 1660 were registered with incident
      MI, 958 with T2DM, 2410 with cancer and 4318 had died. Subjects with the DBP
      phenotype 1f/1f had 23 - 26 % reduced risk of incident cancer compared to the
      1s/1s and 2/2 phenotypes (P < 0.02, Cox regression with gender as covariate).
      Differences in serum 25(OH)D levels could not explain the apparent cancer
      protective effect of the DBP variant 1f. In addition to cancer and 25(OH)D, there
      were significant associations between DBP phenotype and body height, hip
      circumference and serum calcium. CONCLUSION: There are important biological
      differences between the common DBP phenotypes. If the relation between the DBP
      variant 1f and cancer is confirmed in other studies, determination of DBP
      phenotype may have clinical importance.

PMID- 25993555
TI  - Quantitative high-throughput identification of drugs as modulators of human
      constitutive androstane receptor.
AB  - The constitutive androstane receptor (CAR, NR1I3) plays a key role in governing
      the transcription of numerous hepatic genes that involve xenobiotic
      metabolism/clearance, energy homeostasis, and cell proliferation. Thus,
      identification of novel human CAR (hCAR) modulators may not only enhance early
      prediction of drug-drug interactions but also offer potentially novel
      therapeutics for diseases such as metabolic disorders and cancer. In this study,
      we have generated a double stable cell line expressing both hCAR and a CYP2B6
      driven luciferase reporter for quantitative high-throughput screening (qHTS) of
      hCAR modulators. Approximately 2800 compounds from the NIH Chemical Genomics
      Center Pharmaceutical Collection were screened employing both the activation and
      deactivation modes of the qHTS. Activators (115) and deactivators (152) of hCAR
      were identified from the primary qHTS, among which 10 agonists and 10 antagonists
      were further validated in the physiologically relevant human primary hepatocytes
      for compound-mediated hCAR nuclear translocation and target gene expression.
      Collectively, our results reveal that hCAR modulators can be efficiently
      identified through this newly established qHTS assay. Profiling drug collections
      for hCAR activity would facilitate the prediction of metabolism-based drug-drug
      interactions, and may lead to the identification of potential novel therapeutics.

PMID- 25993556
TI  - Risk of end-stage renal disease after cancer nephrectomy in Taiwan: a nationwide
      population-based study.
AB  - BACKGROUND: The conclusions of population-based studies examining the risk of
      developing end-stage renal disease (ESRD) after nephrectomy among patients with
      renal cell carcinoma (RCC) remain inconclusive. In this study, we sought to
      examine whether patients with RCC undergoing radical nephrectomy (RN) have higher
      risk of ESRD compared to those undergoing partial nephrectomy (PN). METHODS:
      Nationwide population-based retrospective cohort of 7670 patients with RCC who
      underwent RN or PN between 2000 and 2011 as recorded in the Taiwan National
      Health Insurance in-patient claims data were analyzed. The primary outcome of
      interest was the occurrence of ESRD requiring regular renal hemodialysis.
      Multivariable Cox proportional hazard regression model was performed to assess
      the risk. FINDINGS: The median follow-up for the post-propensity matched cohort
      (1212 PN and 2424 RN) was 48 months. Seventy patients (2.9%) developed ESRD among
      those who underwent RN, for an incidence rate of 6.9 cases per 1000 person-years.
      In contrast, only 23 patients (1.9%) developed ESRD among patients who underwent
      PN, for an incidence rate of 5.5 cases per 1000 person-years. Despite the higher
      incidence rate of ESRD among RN, the aIRR (RN/PN) was 1.26 (95% CI 0.78-2.01),
      which was not statistically significant. CONCLUSIONS: This Taiwan nationwide
      population-based study suggests that patients with RCC undergoing RN do not have
      significantly higher risk of developing ESRD compared to those undergoing PN.

PMID- 25993557
TI  - Acid-Labile Poly(glycidyl methacrylate)-Based Star Gene Vectors.
AB  - It was recently reported that ethanolamine-functionalized poly(glycidyl
      methacrylate) (PGEA) possesses great potential applications in gene therapy due
      to its good biocompatibility and high transfection efficiency. Importing
      responsivity into PGEA vectors would further improve their performances. Herein,
      a series of responsive star-shaped vectors, acetaled beta-cyclodextrin-PGEAs (A
      CD-PGEAs) consisting of a beta-CD core and five PGEA arms linked by acid-labile
      acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A
      CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD
      PGEAs/pDNA complexes, and the star structure could decrease charge density. The
      incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and
      degradation. In weakly acidic endosome, the broken acetal linkers resulted in
      decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA
      complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison
      with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly
      better transfection performances. 

PMID- 25993560
TI  - Creation of Novel Solid-Solution Alloy Nanoparticles on the Basis of Density-of
      States Engineering by Interelement Fusion.
AB  - Currently 118 known elements are represented in the periodic table. Of these 118
      elements, only about 80 elements are stable, nonradioactive, and widely available
      for our society. From the viewpoint of the "elements strategy", we need to make
      full use of the 80 elements to bring out their latent ability and create
      innovative materials. Furthermore, there is a strong demand that the use of rare
      or toxic elements be reduced or replaced while their important properties are
      retained. Advanced science and technology could create higher-performance
      materials even while replacing or reducing minor or harmful elements through the
      combination of more abundant elements. The properties of elements are correlated
      directly with their electronic states. In a solid, the magnitude of the density
      of states (DOS) at the Fermi level affects the physical and chemical properties.
      In the present age, more attention has been paid to improving the properties of
      materials by means of alloying elements. In particular, the solid-solution-type
      alloy is advantageous because the properties can be continuously controlled by
      tuning the compositions and/or combinations of the constituent elements. However,
      the majority of bulk alloys are of the phase-separated type under ambient
      conditions, where constituent elements are immiscible with each other. To
      overcome the challenge of the bulk-phase metallurgical aspects, we have focused
      on the nanosize effect and developed methods involving "nonequilibrium synthesis"
      or "a process of hydrogen absorption/desorption". We propose a new concept of
      "density-of-states engineering" for the design of materials having the most
      desirable and suitable properties by means of "interelement fusion". In this
      Account, we describe novel solid-solution alloys of Pd-Pt, Ag-Rh, and Pd-Ru
      systems in which the constituent elements are immiscible in the bulk state. The
      homogeneous solid-solution alloys of Pd and Pt were created from Pd core/Pt shell
      nanoparticles using a hydrogen absorption/desorption process as a trigger.
      Several atom percent replacements of Pd with Pt atoms resulted in a significantly
      enhanced hydrogen absorption capacity compared with Pd nanoparticles. AgxRh1-x
      and PdxRu1-x solid-solution alloy nanoparticles were also developed by
      nonequilibrium synthesis based on a polyol method. The AgxRh1-x nanoparticles
      demonstrated hydrogen storage properties, although pure metal nanoparticles of
      each constituent element do not adsorb hydrogen. AgxRh1-x is therefore considered
      to possess a similar electronic structure to Pd as a synthetic pseudo-palladium.
      The PdxRu1-x nanoparticles showed enhanced catalytic activity for CO oxidation,
      with the highest catalytic activity found using the equimolar Pd0.5Ru0.5
      nanoparticles. The catalytic activity of the Pd0.5Ru0.5 nanoparticles exceeds
      that of the widely used and best-performing Ru catalysts for CO oxidation and is
      also higher than that of neighboring Rh on the periodic table. Our present work
      provides a guiding principle for the design of a suitable DOS shape according to
      the intended physical and/or chemical properties and a method for the development
      of novel solid-solution alloys. 

PMID- 25993559
TI  - Thalamic theta phase alignment predicts human memory formation and anterior
      thalamic cross-frequency coupling.
AB  - Previously we reported electrophysiological evidence for a role for the anterior
      thalamic nucleus (ATN) in human memory formation (Sweeney-Reed et al., 2014).
      Theta-gamma cross-frequency coupling (CFC) predicted successful memory formation,
      with the involvement of gamma oscillations suggesting memory-relevant local
      processing in the ATN. The importance of the theta frequency range in memory
      processing is well-established, and phase alignment of oscillations is considered
      to be necessary for synaptic plasticity. We hypothesized that theta phase
      alignment in the ATN would be necessary for memory encoding. Further analysis of
      the electrophysiological data reveal that phase alignment in the theta rhythm was
      greater during successful compared with unsuccessful encoding, and that this
      alignment was correlated with the CFC. These findings support an active
      processing role for the ATN during memory formation. 

PMID- 25993558
TI  - A functional link between the co-translational protein translocation pathway and
      the UPR.
AB  - Upon endoplasmic reticulum (ER) stress, the transmembrane endoribonuclease
      Ire1alpha performs mRNA cleavage reactions to increase the ER folding capacity.
      It is unclear how the low abundant Ire1alpha efficiently finds and cleaves the
      majority of mRNAs at the ER membrane. Here, we reveal that Ire1alpha forms a
      complex with the Sec61 translocon to cleave its mRNA substrates. We show that
      Ire1alpha's key substrate, XBP1u mRNA, is recruited to the Ire1alpha-Sec61
      translocon complex through its nascent chain, which contains a pseudo
      transmembrane domain to utilize the signal recognition particle (SRP)-mediated
      pathway. Depletion of SRP, the SRP receptor or the Sec61 translocon in cells
      leads to reduced Ire1alpha-mediated splicing of XBP1u mRNA. Furthermore,
      mutations in Ire1alpha that disrupt the Ire1alpha-Sec61 complex causes reduced
      Ire1alpha-mediated cleavage of ER-targeted mRNAs. Thus, our data suggest that the
      Unfolded Protein Response is coupled with the co-translational protein
      translocation pathway to maintain protein homeostasis in the ER during stress
      conditions. 

PMID- 25993561
TI  - Structural Insights into Substrate Specificity of Feruloyl-CoA 6'-Hydroxylase
      from Arabidopsis thaliana.
AB  - Coumarins belong to an important class of plant secondary metabolites. Feruloyl
      CoA 6'-hydroxylase (F6'H), a 2-oxoglutarate dependent dioxygenase (2OGD),
      catalyzes a pivotal step in the biosynthesis of a simple coumarin scopoletin. In
      this study, we determined the 3-dimensional structure of the F6'H1 apo enzyme by
      X-ray crystallography. It is the first reported structure of a 2OGD enzyme
      involved in coumarin biosynthesis and closely resembles the structure of
      Arabidopsis thaliana anthocyanidin synthase. To better understand the mechanism
      of enzyme catalysis and substrate specificity, we also generated a homology model
      of a related ortho-hydroxylase (C2'H) from sweet potato. By comparing these two
      structures, we targeted two amino acid residues and verified their roles in
      substrate binding and specificity by site-directed mutagenesis. 

PMID- 25993562
TI  - RulNet: A Web-Oriented Platform for Regulatory Network Inference, Application to
      Wheat -Omics Data.
AB  - With the increasing amount of -omics data available, a particular effort has to
      be made to provide suitable analysis tools. A major challenge is that of
      unraveling the molecular regulatory networks from massive and heterogeneous
      datasets. Here we describe RulNet, a web-oriented platform dedicated to the
      inference and analysis of regulatory networks from qualitative and quantitative 
      omics data by means of rule discovery. Queries for rule discovery can be written
      in an extended form of the RQL query language, which has a syntax similar to SQL.
      RulNet also offers users interactive features that progressively adjust and
      refine the inferred networks. In this paper, we present a functional
      characterization of RulNet and compare inferred networks with correlation-based
      approaches. The performance of RulNet has been evaluated using the three
      benchmark datasets used for the transcriptional network inference challenge
      DREAM5. Overall, RulNet performed as well as the best methods that participated
      in this challenge and it was shown to behave more consistently when compared
      across the three datasets. Finally, we assessed the suitability of RulNet to
      analyze experimental -omics data and to infer regulatory networks involved in the
      response to nitrogen and sulfur supply in wheat (Triticum aestivum L.) grains.
      The results highlight putative actors governing the response to nitrogen and
      sulfur supply in wheat grains. We evaluate the main characteristics and features
      of RulNet as an all-in-one solution for RN inference, visualization and editing.
      Using simple yet powerful RulNet queries allowed RNs involved in the adaptation
      of wheat grain to N and S supply to be discovered. We demonstrate the
      effectiveness and suitability of RulNet as a platform for the analysis of RNs
      involving different types of -omics data. The results are promising since they
      are consistent with what was previously established by the scientific community. 

PMID- 25993563
TI  - Haemodiafiltration, haemofiltration and haemodialysis for end-stage kidney
      disease.
AB  - BACKGROUND: Convective dialysis modalities (haemofiltration (HF),
      haemodiafiltration (HDF), and acetate-free biofiltration (AFB)) removed excess
      body fluid across the dialysis membrane with positive pressure and accumulated
      middle- and larger-size accumulated solutes more efficiently than haemodialysis
      (HD). This increased larger solute removal combined with use of ultra-pure
      dialysis fluid in convective dialysis is hypothesised to reduce the frequency and
      severity of symptoms during dialysis as well as improve clinical outcomes.
      Convective dialysis therapies (HDF and HF) are associated with lower mortality
      compared to diffusive therapy (HD) in observational studies. This is an update of
      a review first published in 2006. OBJECTIVES: To compare convective (HF, HDF, or
      AFB) with diffusive (HD) dialysis modalities on clinical outcomes (mortality,
      major cardiovascular events, hospitalisation and treatment-related adverse
      events) in men and women with end-stage kidney disease (ESKD). SEARCH METHODS: We
      searched the Cochrane Renal Group's Specialised Register (to 18 February 2015)
      through contact with a Trials' Search Co-ordinator using search terms relevant to
      this review. SELECTION CRITERIA: We included randomised controlled trials
      comparing convective therapy (HF, HDF, AFB) with another convective therapy or
      diffusive therapy (HD) for treatment of ESKD. DATA COLLECTION AND ANALYSIS: Two
      independent authors identified studies, extracted data and assessed study risk of
      bias. We summarised treatment effects using the random effects model. We reported
      results as a risk ratio (RR) for dichotomous outcomes and mean difference (MD)
      for continuous data together with 95% confidence intervals (CI). We assessed for
      heterogeneity using the Chi(2) test and explored the amount of variation in
      treatment estimates beyond that expected by chance using the I(2) statistic. MAIN
      RESULTS: Twenty studies comprising 667 participants were included in the 2006
      review. In that review, there was insufficient evidence of treatment effects on
      major clinical outcomes to draw clinically meaningful conclusions. Searching to
      February 2015 identified 40 eligible studies comprising 3483 participants
      overall. In total, 35 studies (4039 participants) compared HF, HDF or AFB with
      HD, three studies (54 participants) compared AFB with HDF, and three studies (129
      participants) compared HDF with HF.Risks of bias in all studies were generally
      high resulting in low confidence in estimated treatment effects. Convective
      dialysis had no significant effect on all-cause mortality (11 studies, 3396
      participants: RR 0.87, 95% CI 0.72 to 1.05; I(2) = 34%), but significantly
      reduced cardiovascular mortality (6 studies, 2889 participants: RR 0.75, 95% CI
      0.61 to 0.92; I(2) = 0%). One study reported no significant effect on rates of
      nonfatal cardiovascular events (714 participants: RR 1.14, 95% CI 0.86 to 1.50)
      and two studies showed no significant difference in hospitalisation (2 studies,
      1688 participants: RR 1.23, 95% CI 0.93 to 1.63; I(2) = 0%). One study reported
      rates of hypotension during dialysis were significantly reduced with convective
      therapy (906 participants: RR 0.72, 95% CI 0.66 to 0.80). Adverse events were not
      systematically evaluated in most studies and data for health-related quality of
      life were sparse. Convective therapies significantly reduced predialysis levels
      of B2 microglobulin (12 studies, 1813 participants: MD -5.55 mg/dL, 95% CI -9.11
      to -1.98; I(2) = 94%) and increased dialysis dose (Kt/V urea) (14 studies, 2022
      participants: MD 0.07, 95% CI -0.00 to 0.14; I(2) = 90%) compared to diffusive
      therapy, but results across studies were very heterogeneous. Sensitivity analyses
      limited to studies comparing HDF with HD showed very similar results. Directly
      comparative data for differing types of convective dialysis were insufficient to
      draw conclusions.Studies had important risks of bias leading to low confidence in
      the summary estimates and were generally limited to patients who had adequate
      dialysis vascular access. AUTHORS' CONCLUSIONS: Convective dialysis may reduce
      cardiovascular but not all-cause mortality and effects on nonfatal cardiovascular
      events and hospitalisation are inconclusive. However, any treatment benefits of
      convective dialysis on all patient outcomes including cardiovascular death are
      unreliable due to limitations in study methods and reporting. Future studies
      which assess treatment effects of convection dose on patient outcomes including
      mortality and cardiovascular events would be informative.

PMID- 25993565
TI  - The Relationship between Non-Suicidal Self-Injury and the UPPS-P Impulsivity
      Facets in Eating Disorders and Healthy Controls.
AB  - In the present study, we investigated the association between Non-Suicidal Self
      Injury (NSSI) and the UPPS-P impulsivity facets in eating disorder patients and
      healthy controls. The prevalence of NSSI in eating disorder (ED) patients ranged
      from 17% in restrictive anorexia nervosa (AN-R) patients to 43% in patients with
      bulimia nervosa (BN). In healthy controls (HC), the prevalence of NSSI was 19%.
      Eating disorder patients from the binge eating/purging type showed significantly
      more NSSI compared to restrictive ED and HC participants. Binge-eating/purging ED
      patients also scored significantly higher on Negative/Positive Urgency, Lack of
      Premeditation and Lack of Perseverance compared to HC and restrictive ED
      patients. Comparable findings were found between ED patients and HC with and
      without NSSI; ED patients and HC with NSSI scored significantly higher in four of
      the five UPPS-P dimensions compared to participants without NSSI; Sensation
      Seeking was the exception. Finally, the presence of NSSI in HC/ED patients was
      particularly predicted by low levels of Perseverance. Therefore, the treatment of
      ED patients with NSSI certainly needs to focus on the training of effortful
      control. 

PMID- 25993566
TI  - Adaptive Tensor-Based Principal Component Analysis for Low-Dose CT Image
      Denoising.
AB  - Computed tomography (CT) has a revolutionized diagnostic radiology but involves
      large radiation doses that directly impact image quality. In this paper, we
      propose adaptive tensor-based principal component analysis (AT-PCA) algorithm for
      low-dose CT image denoising. Pixels in the image are presented by their nearby
      neighbors, and are modeled as a patch. Adaptive searching windows are calculated
      to find similar patches as training groups for further processing. Tensor-based
      PCA is used to obtain transformation matrices, and coefficients are sequentially
      shrunk by the linear minimum mean square error. Reconstructed patches are
      obtained, and a denoised image is finally achieved by aggregating all of these
      patches. The experimental results of the standard test image show that the best
      results are obtained with two denoising rounds according to six quantitative
      measures. For the experiment on the clinical images, the proposed AT-PCA method
      can suppress the noise, enhance the edge, and improve the image quality more
      effectively than NLM and KSVD denoising methods. 

PMID- 25993567
TI  - Climatic effects on planning behavior.
AB  - What mechanism links climate change and social change? Palaeoanthropological
      analysis of human remains suggests that abrupt climate change is linked to
      societal restructuring, but it has been challenging to reliably identify the
      exact mechanisms underlying this relationship. Here we identify one potential
      mechanism that can link climate to behavior change, and underpins many of the
      reported findings on social restructuring. Specifically, we show that daily
      weather is linked to human planning behavior, and this effect is moderated by
      climate. Our results demonstrate that as weather gets colder, humans increase
      their planning in cold regions and decrease planning in warm regions. Since
      planning has previously been linked to group efficiency, cooperation, and
      societal organization, our work suggests planning is one mechanism that can link
      climate change to societal restructuring. 

PMID- 25993564
TI  - Orexinergic neurotransmission in temperature responses to methamphetamine and
      stress: mathematical modeling as a data assimilation approach.
AB  - EXPERIMENTAL DATA: Orexinergic neurotransmission is involved in mediating
      temperature responses to methamphetamine (Meth). In experiments in rats, SB
      334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg
      decreases late temperature responses (t > 60 min) to an intermediate dose of Meth
      (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low
      dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates
      early responses (t < 60 min) to intermediate and high doses (5 and 10 mg/kg) of
      Meth. As pretreatment with SB also inhibits temperature response to the stress of
      injection, traditional statistical analysis of temperature responses is
      difficult. MATHEMATICAL MODELING: We have developed a mathematical model that
      explains the complexity of temperature responses to Meth as the interplay between
      excitatory and inhibitory nodes. We have extended the developed model to include
      the stress of manipulations and the effects of SB. Stress is synergistic with
      Meth on the action on excitatory node. Orexin receptors mediate an activation of
      on both excitatory and inhibitory nodes by low doses of Meth, but not on the node
      activated by high doses (HD). Exaggeration of early responses to high doses of
      Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and
      lowers the activation threshold, while the higher dose suppresses the inhibitory
      component. Using a modeling approach to data assimilation appears efficient in
      separating individual components of complex response with statistical analysis
      unachievable by traditional data processing methods.

PMID- 25993568
TI  - On training.

PMID- 25993572
TI  - Ten questions with ....

PMID- 25993569
TI  - The heart of the preventive maintenance debate: a challenge to all members of the
      HTM community.

PMID- 25993575
TI  - Training day.

PMID- 25993574
TI  - Ask George.

PMID- 25993576
TI  - Stay above the fray: how to navigate office politics and personalities.

PMID- 25993577
TI  - An alarm management view of IT and Biomed roles and responsibilities.

PMID- 25993578
TI  - Digital health: bridging the gap between promise and reality.

PMID- 25993580
TI  - Cybersecurity expert: medical devices have 'a long way to go'.

PMID- 25993579
TI  - A roundtable discussion: hopes and hurdles for the unique device identification
      rule.

PMID- 25993581
TI  - Group's deep data dive helps optimize medical equipment maintenance.

PMID- 25993582
TI  - Go back to basics for flow issue.

PMID- 25993584
TI  - The value of rounding in hospitals.

PMID- 25993585
TI  - Effect of altering alarm settings: a randomized controlled study.
AB  - Medical alarm signals are important for alerting clinicians to life-threatening
      conditions, but the high rate of false alarms can be problematic. Reduction in
      alarm signals may lead to increased staff responsiveness to alarms and create a
      quieter environment for patients. The effect of these changes on patient outcomes
      is uncertain. METHODS: We conducted a pilot, prospective, randomized, controlled
      trial in the cardiac care unit (CCU) to test a study protocol and data collection
      instruments and to examine the differences in alarms between usual care and
      altered settings. Subjects were randomized daily to either standard or altered
      CCU alarm settings. Secondary outcomes included the number of clinically
      significant events (CSEs) detected, event-triggered interventions (ETIs),
      frequency of alarms per monitored bed, and patient complications. RESULTS: Over
      the two-week study time frame, 22 unique patients were enrolled. There were 1,710
      alarms over 163 hours of monitoring in the standard group and 1,165 alarms over
      169 hours in the study group (P < 0.001). There were more CSEs detected (14 vs.
      3) and ETIs (12 vs. 2) in the study group, but sample size was too small to
      determine efficacy. No cardiac arrests or adverse patient outcomes were observed
      in either group. All patients were discharged from the hospital. Study protocol
      and outcomes were feasible and lessons were learned. CONCLUSION: This study
      demonstrated feasibility of a study protocol for conducting a randomized
      controlled trial to evaluate CSEs, ETIs, frequency of alarms, and adverse patient
      outcomes when altering default alarm settings. A longer study can be performed
      using a similar study design.

PMID- 25993586
TI  - Adverse events do not happen by accident.

PMID- 25993588
TI  - Infant mortality in Novo Hamburgo: associated factors and cardiovascular causes.
AB  - BACKGROUND: Infant mortality has decreased in Brazil, but remains high as
      compared to that of other developing countries. In 2010, the Rio Grande do Sul
      state had the lowest infant mortality rate in Brazil. However, the municipality
      of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre
      metropolitan region. OBJECTIVE: To describe the causes of infant mortality in the
      municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were
      related to heart diseases and if they were diagnosed in the prenatal period, and
      to assess the access to healthcare services. METHODS: This study assessed infants
      of the municipality of Novo Hamburgo, who died, and whose data were collected
      from the infant death investigation records. RESULTS: Of the 157 deaths in that
      period, 35.3% were reducible through diagnosis and early treatment, 25% were
      reducible through partnership with other sectors, 19.2% were non-preventable,
      11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were
      reducible through appropriate delivery care, and 3.8% were ill defined. The major
      cause of death related to heart disease (13.4%), which was significantly
      associated with the variables 'age at death', 'gestational age' and 'birth
      weight'. Regarding access to healthcare services, 60.9% of the pregnant women had
      a maximum of six prenatal visits. CONCLUSION: It is mandatory to enhance prenatal
      care and newborn care at hospitals and basic healthcare units to prevent infant
      mortality.

PMID- 25993589
TI  - Insulin resistance, dyslipidemia and cardiovascular changes in a group of obese
      children.
AB  - INTRODUCTION: Obesity-related comorbidities are present in young obese children,
      providing a platform for early adult cardiovascular disorders. OBJECTIVES: To
      compare and correlate markers of adiposity to metabolic disturbances, vascular
      and cardiac morphology in a European pediatric obese cohort. METHODS: We carried
      out an observational and transversal analysis in a cohort consisting of 121 obese
      children of both sexes, between the ages of 6 and 17 years. The control group
      consisted of 40 children with normal body mass index within the same age range.
      Markers of adiposity, plasma lipids and lipoproteins, homeostasis model
      assessment-insulin resistance, common carotid artery intima-media thickness and
      left ventricular diameters were analyzed. RESULTS: There were statistically
      significant differences between the control and obese groups for the variables
      analyzed, all higher in the obese group, except for age, high-density lipoprotein
      cholesterol and adiponectin, higher in the control group. In the obese group,
      body mass index was directly correlated to left ventricular mass (r=0.542;
      p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001)
      and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In
      that same group, insulin resistance was present in 38.1%, 12.5% had a combined
      dyslipidemic pattern, and eccentric hypertrophy was the most common left
      ventricular geometric pattern. CONCLUSIONS: These results suggest that these
      markers may be used in clinical practice to stratify cardiovascular risk, as well
      as to assess the impact of weight control programs.

PMID- 25993590
TI  - Subclinical ventricular dysfunction detected by speckle tracking two years after
      use of anthracycline.
AB  - BACKGROUND: Heart failure is a severe complication associated with doxorubicin
      (DOX) use. Strain, assessed by two-dimensional speckle tracking (2D-STE), has
      been shown to be useful in identifying subclinical ventricular dysfunction.
      OBJECTIVES: a) To investigate the role of strain in the identification of
      subclinical ventricular dysfunction in patients who used DOX; b) to investigate
      determinants of strain response in these patients. METHODS: Cross-sectional study
      with 81 participants: 40 patients who used DOX +/- 2 years before the study and
      41 controls. All participants had left ventricular ejection fraction (LVEF) >=
      55%. Total dose of DOX was 396 mg (242 mg/ms2). The systolic function of the LV
      was evaluated by LVEF (Simpson), as well as by longitudinal (epsilonLL),
      circumferential (epsilonCC), and radial (epsilonRR) strains. Multivariate linear
      regression (MLR) analysis was performed using epsilonLL (model 1) and epsilonCC
      (model 2) as dependent variables. RESULTS: Systolic and diastolic blood pressure
      values were higher in the control group (p < 0.05). epsilonLL was lower in the
      DOX group (-12.4 +/- 2.6%) versus controls (-13.4 +/- 1.7%; p = 0.044). The same
      occurred with epsilonCC: -12.1 +/- 2.7% (DOX) versus -16.7 +/- 3.6% (controls; p
      < 0.001). The S' wave was shorter in the DOX group (p = 0.035). On MLR, DOX was
      an independent predictor of reduced epsilonCC (B = -4.429, p < 0.001). DOX (B = 
      1.289, p = 0.012) and age (B = -0.057, p = 0.029) were independent markers of
      reduced epsilonLL. CONCLUSION: a) epsilonLL, epsilonCC and the S' wave are
      reduced in patients who used DOX +/- 2 years prior to the study despite normal
      LVEF, suggesting the presence of subclinical ventricular dysfunction; b) DOX was
      an independent predictor of reduced epsilonCC; c) prior use of DOX and age were
      independent markers of reduced epsilonLL.

PMID- 25993591
TI  - Blood Pressure Variation Throughout Pregnancy According to Early Gestational BMI:
      A Brazilian Cohort.
AB  - BACKGROUND: The maternal cardiovascular system undergoes progressive adaptations
      throughout pregnancy, causing blood pressure fluctuations. However, no consensus
      has been established on its normal variation in uncomplicated pregnancies.
      OBJECTIVE: To describe the variation in systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) levels during pregnancy according to early
      pregnancy body mass index (BMI). METHODS: SBP and DBP were measured during the
      first, second and third trimesters and at 30-45 days postpartum in a prospective
      cohort of 189 women aged 20-40 years. BMI (kg/m2) was measured up to the 13th
      gestational week and classified as normal-weight (<25.0) or excessive weight (>=
      25.0). Longitudinal linear mixed-effects models were used for statistical
      analysis. RESULTS: A decrease in SBP and DBP was observed from the first to the
      second trimester (betaSBP=-0.394; 95%CI: -0.600- -0.188 and betaDBP=-0.617;
      95%CI: -0.780- -0.454), as was an increase in SBP and DBP up to 30-45 postpartum
      days (betaSBP=0.010; 95%CI: 0.006-0.014 and betaDBP=0.015; 95%CI: 0.012-0.018).
      Women with excessive weight at early pregnancy showed higher mean SBP in all
      gestational trimesters, and higher mean DBP in the first and third trimesters.
      Excessive early pregnancy BMI was positively associated with prospective changes
      in SBP (betaSBP=7.055; 95%CI: 4.499-9.610) and in DBP (betaDBP=3.201; 95%CI:
      1.136-5.266). CONCLUSION: SBP and DBP decreased from the first to the second
      trimester and then increased up to the postpartum period. Women with excessive
      early pregnancy BMI had higher SBP and DBP than their normal-weight counterparts
      throughout pregnancy, but not in the postpartum period.

PMID- 25993592
TI  - Progression of blood pressure and cardiovascular outcomes in hypertensive
      patients in a reference center.
AB  - BACKGROUND: Hypertension is a public health problem, considering its high
      prevalence, low control rate and cardiovascular complications. OBJECTIVE:
      Evaluate the control of blood pressure (BP) and cardiovascular outcomes in
      patients enrolled at the Reference Center for Hypertension and Diabetes, located
      in a medium-sized city in the Midwest Region of Brazil. METHODS: Population-based
      study comparing patients enrolled in the service at the time of their admission
      and after an average follow-up of five years. Participants were aged >= 18 years
      and were regularly monitored at the Center up to 6 months before data collection.
      We assessed demographic variables, BP, body mass index, risk factors, and
      cardiovascular outcomes. RESULTS: We studied 1,298 individuals, predominantly
      women (60.9%), and with mean age of 56.7 +/- 13.1 years. Over time, there was a
      significant increase in physical inactivity, alcohol consumption, diabetes,
      dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed
      an increase in stroke and myocardial revascularization, and a lower frequency of
      chronic renal failure. During follow-up, there was significant improvement in the
      rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which
      were due to cardiovascular diseases. CONCLUSION: Despite considerable
      improvements in the rate of BP control during follow-up, risk factors worsened
      and cardiovascular outcomes increased.

PMID- 25993593
TI  - Quality of Life on Arterial Hypertension: Validity of Known Groups of MINICHAL.
AB  - INTRODUCTIONS: In the care of hypertension, it is important that health
      professionals possess available tools that allow evaluating the impairment of the
      health-related quality of life, according to the severity of hypertension and the
      risk for cardiovascular events. Among the instruments developed for the
      assessment of health-related quality of life, there is the Mini-Cuestionario of
      Calidad de Vida en la Hipertension Arterial (MINICHAL) recently adapted to the
      Brazilian culture. OBJECTIVE: To estimate the validity of known groups of the
      Brazilian version of the MINICHAL regarding the classification of risk for
      cardiovascular events, symptoms, severity of dyspnea and target-organ damage.
      METHODS: Data of 200 hypertensive outpatients concerning sociodemographic and
      clinical information and health-related quality of life were gathered by
      consulting the medical charts and the application of the Brazilian version of
      MINICHAL. The Mann-Whitney test was used to compare health-related quality of
      life in relation to symptoms and target-organ damage. The Kruskal-Wallis test and
      ANOVA with ranks transformation were used to compare health-related quality of
      life in relation to the classification of risk for cardiovascular events and
      intensity of dyspnea, respectively. RESULTS: The MINICHAL was able to
      discriminate health-related quality of life in relation to symptoms and kidney
      damage, but did not discriminate health-related quality of life in relation to
      the classification of risk for cardiovascular events. CONCLUSION: The Brazilian
      version of the MINICHAL is a questionnaire capable of discriminating differences
      on the health-related quality of life regarding dyspnea, chest pain, palpitation,
      lipothymy, cephalea and renal damage.

PMID- 25993594
TI  - Influence of spironolactone on matrix metalloproteinase-2 in acute decompensated
      heart failure.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are a family of enzymes important
      for the resorption of extracellular matrices, control of vascular remodeling and
      repair. Increased activity of MMP2 has been demonstrated in heart failure, and in
      acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has
      been demonstrated along with successful treatment. OBJECTIVE: Our aim was to test
      the influence of spironolactone in MMP2 levels. METHODS: Secondary analysis of a
      prospective, interventional study including 100 patients with ADHF. Fifty
      patients were non-randomly assigned to spironolactone (100 mg/day) plus standard
      ADHF therapy (spironolactone group) or standard ADHF therapy alone (control
      group). RESULTS: Spironolactone group patients were younger and had lower
      creatinine and urea levels (all p < 0.05). Baseline MMP2, NT-pro BNP and weight
      did not differ between spironolactone and control groups. A trend towards a more
      pronounced decrease in MMP2 from baseline to day 3 was observed in the
      spironolactone group (-21 [-50 to 19] vs 1.5 [-26 to 38] ng/mL, p = 0.06). NT-pro
      BNP and weight also had a greater decrease in the spironolactone group. The
      proportion of patients with a decrease in MMP2 levels from baseline to day 3 was
      also likely to be greater in the spironolactone group (50% vs 66.7%), but without
      statistical significance. Correlations between MMP2, NT-pro BNP and weight
      variation were not statistically significant. CONCLUSION: MMP2 levels are
      increased in ADHF. Patients treated with spironolactone may have a greater
      reduction in MMP2 levels.

PMID- 25993595
TI  - Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary
      Lumen in Segments with or without Atherosclerotic Plaques.
AB  - BACKGROUND: The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has
      been poorly described and is mainly restricted to reports analyzing segments with
      documented atherosclerotic plaques. OBJECTIVES: We compared 64-slice
      multidetector computed tomography (MDCT) with gray scale intravascular ultrasound
      (IVUS) for the evaluation of coronary lumen dimensions in the context of a
      comprehensive analysis, including segments with absent or mild disease. METHODS:
      The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was
      obtained for at least one coronary, regardless of the presence of luminal
      stenosis at angiography. A total of 21 patients were included, with 70 imaged
      vessels (total length 114.6 +/- 38.3 mm per patient). A coronary plaque was
      diagnosed in segments with plaque burden > 40%. RESULTS: At patient, vessel, and
      segment levels, average lumen area, minimal lumen area, and minimal lumen
      diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01).
      However, 64-slice MDCT tended to underestimate the lumen size with a relatively
      wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS
      lumen measurements was not substantially affected by the presence or absence of
      an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for
      the detection of IVUS parameters associated with flow-limiting lesions.
      CONCLUSIONS: In a comprehensive, multi-territory, and whole-artery analysis, the
      assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed
      a good overall diagnostic ability, regardless of the presence or absence of
      underlying atherosclerotic plaques.

PMID- 25993597
TI  - Left atrial volume index as predictor of events in acute coronary syndrome.

PMID- 25993596
TI  - Treatment of dyslipidemia with statins and physical exercises: recent findings of
      skeletal muscle responses.
AB  - Statin treatment in association with physical exercise practice can substantially
      reduce cardiovascular mortality risk of dyslipidemic individuals, but this
      practice is associated with myopathic event exacerbation. This study aimed to
      present the most recent results of specific literature about the effects of
      statins and its association with physical exercise on skeletal musculature. Thus,
      a literature review was performed using PubMed and SciELO databases, through the
      combination of the keywords "statin" AND "exercise" AND "muscle", restricting the
      selection to original studies published between January 1990 and November 2013.
      Sixteen studies evaluating the effects of statins in association with acute or
      chronic exercises on skeletal muscle were analyzed. Study results indicate that
      athletes using statins can experience deleterious effects on skeletal muscle, as
      the exacerbation of skeletal muscle injuries are more frequent with intense
      training or acute eccentric and strenuous exercises. Moderate physical training,
      in turn, when associated to statins does not increase creatine kinase levels or
      pain reports, but improves muscle and metabolic functions as a consequence of
      training. Therefore, it is suggested that dyslipidemic patients undergoing statin
      treatment should be exposed to moderate aerobic training in combination to
      resistance exercises three times a week, and the provision of physical training
      prior to drug administration is desirable, whenever possible. 

PMID- 25993598
TI  - Case 4/2015. A 48-year-old Male Patient with Coarctation of the Aorta, Bicuspid
      Aortic Valve and Normal Ascending Aorta.

PMID- 25993599
TI  - Sickle-cell Anemia and Latent Diastolic Dysfunction: Echocardiographic
      Alterations.

PMID- 25993600
TI  - Correct anatomical orientation of the heart and reflections on the nomenclature
      used in daily practice.

PMID- 25993601
TI  - Incremental Value Of 3D Transesophageal Echocardiography for The Assessment of
      Mitral Valve Prolapse.

PMID- 25993602
TI  - Pairwise growth competition assay for determining the replication fitness of
      human immunodeficiency viruses.
AB  - In vitro fitness assays are essential tools for determining viral replication
      fitness for viruses such as HIV-1. Various measurements have been used to
      extrapolate viral replication fitness, ranging from the number of viral particles
      per infectious unit, growth rate in cell culture, and relative fitness derived
      from multiple-cycle growth competition assays. Growth competition assays provide
      a particularly sensitive measurement of fitness since the viruses are competing
      for cellular targets under identical growth conditions. There are several
      experimental factors to consider when conducting growth competition assays,
      including the multiplicity of infection (MOI), sampling times, and viral
      detection and fitness calculation methods. Each factor can affect the end result
      and hence must be considered carefully during the experimental design. The
      protocol presented here includes steps from constructing a new recombinant HIV-1
      clone to performing growth competition assays and analyzing the experimental
      results. This protocol utilizes experimental parameter values previously shown to
      yield consistent and robust results. Alternatives are discussed, as some
      parameters need to be adjusted according to the cell type and viruses being
      studied. The protocol contains two alternative viral detection methods to provide
      flexibility as the availability of instruments, reagents and expertise varies
      between laboratories. 

PMID- 25993603
TI  - Widespread recombination, reassortment, and transmission of unbalanced compound
      viral genotypes in natural arenavirus infections.
AB  - Arenaviruses are one of the largest families of human hemorrhagic fever viruses
      and are known to infect both mammals and snakes. Arenaviruses package a large (L)
      and small (S) genome segment in their virions. For segmented RNA viruses like
      these, novel genotypes can be generated through mutation, recombination, and
      reassortment. Although it is believed that an ancient recombination event led to
      the emergence of a new lineage of mammalian arenaviruses, neither recombination
      nor reassortment has been definitively documented in natural arenavirus
      infections. Here, we used metagenomic sequencing to survey the viral diversity
      present in captive arenavirus-infected snakes. From 48 infected animals, we
      determined the complete or near complete sequence of 210 genome segments that
      grouped into 23 L and 11 S genotypes. The majority of snakes were multiply
      infected, with up to 4 distinct S and 11 distinct L segment genotypes in
      individual animals. This S/L imbalance was typical: in all cases intrahost L
      segment genotypes outnumbered S genotypes, and a particular S segment genotype
      dominated in individual animals and at a population level. We corroborated
      sequencing results by qRT-PCR and virus isolation, and isolates replicated as
      ensembles in culture. Numerous instances of recombination and reassortment were
      detected, including recombinant segments with unusual organizations featuring 2
      intergenic regions and superfluous content, which were capable of stable
      replication and transmission despite their atypical structures. Overall, this
      represents intrahost diversity of an extent and form that goes well beyond what
      has been observed for arenaviruses or for viruses in general. This diversity can
      be plausibly attributed to the captive intermingling of sub-clinically infected
      wild-caught snakes. Thus, beyond providing a unique opportunity to study
      arenavirus evolution and adaptation, these findings allow the investigation of
      unintended anthropogenic impacts on viral ecology, diversity, and disease
      potential. 

PMID- 25993605
TI  - Method for measuring the activity of deubiquitinating enzymes in cell lines and
      tissue samples.
AB  - The ubiquitin-proteasome system has recently been implicated in various
      pathologies including neurodegenerative diseases and cancer. In light of this,
      techniques for studying the regulatory mechanism of this system are essential to
      elucidating the cellular and molecular processes of the aforementioned diseases.
      The use of hemagglutinin derived ubiquitin probes outlined in this paper serves
      as a valuable tool for the study of this system. This paper details a method that
      enables the user to perform assays that give a direct visualization of
      deubiquitinating enzyme activity. Deubiquitinating enzymes control proteasomal
      degradation and share functional homology at their active sites, which allows the
      user to investigate the activity of multiple enzymes in one assay. Lysates are
      obtained through gentle mechanical cell disruption and incubated with active site
      directed probes. Functional enzymes are tagged with the probes while inactive
      enzymes remain unbound. By running this assay, the user obtains information on
      both the activity and potential expression of multiple deubiquitinating enzymes
      in a fast and easy manner. The current method is significantly more efficient
      than using individual antibodies for the predicted one hundred deubiquitinating
      enzymes in the human cell. 

PMID- 25993606
TI  - Perspectives in pediatric pathology, chapter 4. Pubertal and adult testis.

PMID- 25993604
TI  - The evolving role of dendritic spines and memory: Interaction(s) with estradiol.
AB  - This article is part of a Special Issue "Estradiol and Cognition". Memory
      processing is presumed to depend on synaptic plasticity, which appears to have a
      role in mediating the acquisition, consolidation, and retention of memory. We
      have studied the relationship between estrogen, recognition memory, and dendritic
      spine density in the hippocampus and medial prefrontal cortex, areas critical for
      memory, across the lifespan in female rodents. The present paper reviews the
      literature on dendritic spine plasticity in mediating both short and long term
      memory, as well as the decreased memory that occurs with aging and Alzheimer's
      disease. It also addresses the role of acute and chronic estrogen treatments in
      these processes. 

PMID- 25993608
TI  - Repositioning of Memantine as a Potential Novel Therapeutic Agent against
      Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7
      Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host
      Inflammatory Responses.
AB  - Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of
      mortality and morbidity in newborn infants despite the availability of
      antibiotics over the last several decades. E. coli is the most common gram
      negative pathogen causing NSM. Our previous studies show that alpha7 nicotinic
      receptor (alpha7 nAChR), an essential regulator of inflammation, plays a
      detrimental role in the host defense against NSM. Despite notable successes,
      there still exists an unmet need for new effective therapeutic approaches to
      treat this disease. Using the in vitro/in vivo models of the blood-brain barrier
      (BBB) and RNA-seq, we undertook a drug repositioning study to identify unknown
      antimicrobial activities for known drugs. We have demonstrated for the first time
      that memantine (MEM), a FDA-approved drug for treatment of Alzheimer's disease,
      could very efficiently block E. coli-caused bacteremia and meningitis in a mouse
      model of NSM in a manner dependent on alpha7 nAChR. MEM was able to
      synergistically enhance the antibacterial activity of ampicillin in HBMEC
      infected with E. coli K1 (E44) and in neonatal mice with E44-caused bacteremia
      and meningitis. Differential gene expression analysis of RNA-Seq data from mouse
      BMEC infected with E. coli K1 showed that several E44-increased inflammatory
      factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by
      MEM compared to the infected cells without drug treatment. MEM could also
      significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH,
      Ptgds and Zfp36. Most interestingly, these factors may positively and negatively
      contribute to regulation of NF-kappaB, which is a hallmark feature of bacterial
      meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC) are
      the potential novel biomarkers for NSM. MEM could significantly reduce E44
      increased blood level of cBMEC in mice. Taken together, our data suggest that
      memantine can efficiently block host inflammatory responses to bacterial
      infection through modulation of both inflammatory and anti-inflammatory pathways.

PMID- 25993609
TI  - A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the
      Efficacy and Safety of Repeated OnabotulinumtoxinA Treatments in Subjects With
      Crow's Feet Lines and Glabellar Lines.
AB  - BACKGROUND: This is the third study in a Phase 3 program evaluating
      onabotulinumtoxinA treatment of crow's feet lines (CFL). OBJECTIVE: To assess the
      efficacy and safety of repeated onabotulinumtoxinA treatments of CFL alone or
      with glabellar lines (GL) in subjects with moderate-to-severe CFL and GL (maximum
      smile). MATERIALS AND METHODS: This 5-month extension of a 7-month study
      randomized subjects who originally received onabotulinumtoxinA 24 U (CFL only; n
      = 227) or 44 U (24 U for CFL + 20 U for GL; n = 260) to retreatment with the same
      dose. Placebo-treated subjects were rerandomized to onabotulinumtoxinA 44 U (n =
      101) or placebo (n = 96). Primary efficacy end point (Day 30) was the proportion
      of subjects who achieved a CFL severity rating of none or mild (maximum smile) on
      the investigator-assessed Facial Wrinkle Scale (FWS). Additional efficacy end
      points and adverse events were evaluated. RESULTS: Responder rates (primary end
      point) were significantly greater in onabotulinumtoxinA-treated groups (24 U:
      56.5%; 44 U: 63.6%; placebo: 1.1%; p < .001). Improvements on most patient
      reported outcomes (PROs) favored the 44-U group over the 24-U group. Adverse
      events did not differ among groups; most were mild or moderate. CONCLUSION:
      Repeated onabotulinumtoxinA treatments significantly reduce CFL severity based on
      FWS and PROs. Adverse event profiles remain consistent with approved GL labeling.

PMID- 25993610
TI  - Commentary on Impact of Postreconstitution Room Temperature Storage on the
      Efficacy of IncobotulinumtoxinA Treatment of Dynamic Lateral Canthus Lines.

PMID- 25993611
TI  - Outcomes of polydioxanone knotless thread lifting for facial rejuvenation.
AB  - BACKGROUND: Thread lifting is a minimally invasive technique for facial
      rejuvenation. Various devices for thread lifting using polydioxanone (PDO) are
      popular in aesthetic clinics in Korea, but there have been a few studies
      regarding its use. OBJECTIVE: To describe PDO thread and techniques adopted to
      counteract the descent and laxity of the face. METHODS: A retrospective chart
      review was conducted over a 24-month period. A total of 31 thread lifting
      procedures were performed. On each side, 5 bidirectional cog threads were used in
      the procedure for the flabby skin of the nasolabial folds. And, the procedure was
      performed on the marionette line using 2 twin threads. RESULTS: In most patients
      (87%), the results obtained were considered satisfactory. Consensus ratings by 2
      physicians found that objective outcomes were divided among "excellent," "good,"
      "fair," and "poor." Texture wise, the outcome ratings were 13 as excellent and 9
      as good. Lifting wise, ratings were 11 as excellent and 6 as good. The incidence
      of complications was low and not serious. CONCLUSION: Facial rejuvenation using
      PDO thread is a safe and effective procedure associated with only minor
      complications when performed on patients with modest face sagging, fine wrinkles,
      and marked facial pores.

PMID- 25993612
TI  - Painful subcutaneous fibrosis: a complication after high-intensity focused
      ultrasound for lipolysis.

PMID- 25993613
TI  - A case of multiple large reactive keratoacanthomas treated with serial zinc oxide
      wraps.

PMID- 25993614
TI  - Laser skin resurfacing during isotretinoin therapy.

PMID- 25993607
TI  - Meta-analysis of Genome-wide Association Studies for Neuroticism, and the
      Polygenic Association With Major Depressive Disorder.
AB  - IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It
      genetically overlaps with major depressive disorder (MDD) and is therefore an
      important phenotype for psychiatric genetics. The Genetics of Personality
      Consortium has created a resource for genome-wide association analyses of
      personality traits in more than 63,000 participants (including MDD cases).
      OBJECTIVES: To identify genetic variants associated with neuroticism by
      performing a meta-analysis of genome-wide association results based on 1000
      Genomes imputation; to evaluate whether common genetic variants as assessed by
      single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by
      estimating SNP-based heritability; and to examine whether SNPs that predict
      neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide
      association meta-analysis of 30 cohorts with genome-wide genotype, personality,
      and MDD data from the Genetics of Personality Consortium. The study included
      63,661 participants from 29 discovery cohorts and 9786 participants from a
      replication cohort. Participants came from Europe, the United States, or
      Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND
      MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item
      response theory analysis, and clinical MDD case-control status in 2 of the
      cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1
      (rs35855737; P = 9.26 * 10-9 in the discovery meta-analysis). This association
      was not replicated (P = .32), but the SNP was still genome-wide significant in
      the meta-analysis of all 30 cohorts (P = 2.38 * 10-8). Common genetic variants
      explain 15% of the variance in neuroticism. Polygenic scores based on the meta
      analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 *
      10-12 < P < .05) and MDD (4.02 * 10-9 < P < .05) in the 2 other cohorts.
      CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.
      The variant is located in a known gene that has been associated with bipolar
      disorder and schizophrenia in previous studies. In addition, the study shows that
      neuroticism is influenced by many genetic variants of small effect that are
      either common or tagged by common variants. These genetic variants also influence
      MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism
      and further investigate the association of MAGI1 and the polygenic association to
      a range of other psychiatric disorders that are phenotypically correlated with
      neuroticism.

PMID- 25993615
TI  - Magnetic resonance enterographic predictors of one-year outcome in ileal and
      ileocolonic Crohn's disease treated with anti-tumor necrosis factor antibodies.
AB  - The aim of the study was to assess the role of magnetic resonance enterography
      (MRE) in predicting one-year efficacy of anti-tumor necrosis factor antibodies-
      infliximab (IFX), adalimumab (ADA) in Crohn's disease (CD) patients primarily
      responding to therapy. We performed retrospective analysis among 61 CD patients
      who had undergone a successful IFX/ADA induction therapy and were treated with
      maintenance doses. All patients underwent MRE at week 0. We assessed which MRE
      features were predictive for steroid-free remission at week 52, and which were
      associated with a secondary loss of response. 44 patients were in steroid-free
      remission at week 52, 17--were secondary non-responders. The ROC curve showed
      that bowel thickening with contrast enhancement analyzed together at week 0 were
      associated with steroid-free remission at week 52 (p = 0.01; AUC 0.67). Bowel
      stenosis with or without prestenotic dilatation [OR 5.8 (95% CI 1.4-25) and 2.4
      (95% CI 1.2 - 5) respectively; p = 0.01] and the presence of intra-abdominal
      fistulas [OR 1.4 (95% CI 1.1-2); p=0.004] were related to secondary non-response.
      A high baseline inflammatory activity detected by MRE predicts one-year response
      in CD after IFX/ADA. In case of bowel stenosis, intra-abdominal fistulas, other
      therapeutic options should be considered.

PMID- 25993616
TI  - Cervical microbiota in women with preterm prelabor rupture of membranes.
AB  - OBJECTIVE: To analyze the cervical microbiota in women with preterm prelabor
      rupture of membranes (PPROM) by pyrosequencing and to document associations
      between cervical microbiota, cervical inflammatory response, microbial invasion
      of the amniotic cavity (MIAC), histological chorioamnionitis, and intraamniotic
      infection (IAI). STUDY DESIGN: Sixty-one women with singleton pregnancies
      complicated by PPROM were included in the study. Specimens of cervical and
      amniotic fluid were collected on admission. The cervical microbiota was assessed
      by 16S rRNA gene sequencing by pyrosequencing. Interleukin (IL)-6 concentration
      in the cervical fluid and amniotic fluid was measured by ELISA and lateral flow
      immunoassay, respectively. RESULTS: Four bacterial community state types [CST I
      (Lactobacillus crispatus dominated), CST III (Lactobacillus iners dominated), CST
      IV-A (non-Lactobacillus bacteria dominated), and CST IV-B (Gardnerella vaginalis
      and Sneathia sanguinegens dominated)] were observed in the cervical microbiota of
      women with PPROM. Cervical fluid IL-6 concentrations differed between CSTs (CST I
      = 145 pg/mL, CST III = 166 pg/mL, CST IV-A = 420 pg/mL, and CST IV-B = 322 pg/mL;
      p = 0.004). There were also differences in the rates of MIAC, of both MIAC and
      histological chorioamnionitis, and of IAI among CSTs. No difference in the rate
      of histological chorioamnionitis was found among CSTs. CONCLUSIONS: The cervical
      microbiota in PPROM women in this study was characterized by four CSTs. The
      presence of non-Lactobacillus CSTs was associated with a strong cervical
      inflammatory response and higher rates of MIAC, both MIAC and histological
      chorioamnionitis, and IAI representing a PPROM subtype with pronounced
      inflammation. CST I represents the dominant type of PPROM with a low rate of
      MIAC, IAI, and the combination of MIAC and histological chorioamnionitis.

PMID- 25993618
TI  - Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune
      Disease.
AB  - Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid
      oligonucleotides generated in vitro based on affinity for certain target
      molecules by a process known as Systematic Evolution of Ligands by Exponential
      Enrichment. Aptamers can bind their target molecules with high specificity and
      selectivity by means of structure compatibility, stacking of aromatic rings,
      electrostatic and van der Waals interactions, and hydrogen bonding. With several
      advantages over monoclonal antibodies and other conventional small-molecule
      therapeutics, such as high specificity and affinity, negligible batch to batch
      variation, flexible modification and stability, lack of toxicity and low
      immunogenicity, aptamers are becoming promising novel diagnostic and therapeutic
      agents. This review focuses on the development of aptamers as potential
      therapeutics for autoimmune diseases, including diabetes mellitus, multiple
      sclerosis, rheumatoid arthritis, myasthenia gravis, and systemic lupus
      erythematosus. 

PMID- 25993617
TI  - Contribution of EGFR and ErbB-3 Heterodimerization to the EGFR Mutation-Induced
      Gefitinib- and Erlotinib-Resistance in Non-Small-Cell Lung Carcinoma Treatments.
AB  - EGFR mutation-induced drug resistance has become a major threat to the treatment
      of non-small-cell lung carcinoma. Essentially, the resistance mechanism involves
      modifications of the intracellular signaling pathways. In our work, we separately
      investigated the EGFR and ErbB-3 heterodimerization, regarded as the origin of
      intracellular signaling pathways. On one hand, we combined the molecular
      interaction in EGFR heterodimerization with that between the EGFR tyrosine kinase
      and its inhibitor. For 168 clinical subjects, we characterized their
      corresponding EGFR mutations using molecular interactions, with three potential
      dimerization partners (ErbB-2, IGF-1R and c-Met) of EGFR and two of its small
      molecule inhibitors (gefitinib and erlotinib). Based on molecular dynamics
      simulations and structural analysis, we modeled these mutant-partner or mutant
      inhibitor interactions using binding free energy and its components. As a
      consequence, the mutant-partner interactions are amplified for mutants L858R and
      L858R_T790M, compared to the wild type EGFR. Mutant delL747_P753insS represents
      the largest difference between the mutant-IGF-1R interaction and the mutant
      inhibitor interaction, which explains the shorter progression-free survival of an
      inhibitor to this mutant type. Besides, feature sets including different energy
      components were constructed, and efficient regression trees were applied to map
      these features to the progression-free survival of an inhibitor. On the other
      hand, we comparably examined the interactions between ErbB-3 and its partners
      (EGFR mutants, IGF-1R, ErbB-2 and c-Met). Compared to others, c-Met shows a
      remarkably-strong binding with ErbB-3, implying its significant role in
      regulating ErbB-3 signaling. Moreover, EGFR mutants corresponding to poor
      clinical outcomes, such as L858R_T790M, possess lower binding affinities with
      ErbB-3 than c-Met does. This may promote the communication between ErbB-3 and c
      Met in these cancer cells. The analysis verified the important contribution of
      IGF-1R or c-Met in the drug resistance mechanism developed in lung cancer
      treatments, which may bring many benefits to specialized therapy design and
      innovative drug discovery. 

PMID- 25993619
TI  - Discovery of Tricyclic Clerodane Diterpenes as Sarco/Endoplasmic Reticulum Ca(2+)
      ATPase Inhibitors and Structure-Activity Relationships.
AB  - Tricyclic clerodane diterpenes (TCDs) are natural compounds that often show
      potent cytotoxicity for cancer cells, but their mode of action remains elusive. A
      computationally based similarity search (CDRUG), combined with principal
      component analysis (ChemGPS-NP) and docking calculations (GOLD 5.2), suggested
      TCDs to be inhibitors of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA)
      pump, which is also the target of the sesquiterpene lactone thapsigargin.
      Biochemical studies were performed with 11 TCDs on purified rabbit skeletal
      muscle sarcoplasmic reticulum membranes, which are highly enriched with the
      SERCA1a isoform. Casearborin D (2) exhibited the highest affinity, with a KD
      value of 2 MUM and giving rise to complete inhibition of SERCA1a activity.
      Structure-activity relationships revealed that functionalization of two acyl side
      chains (R1 and R4) and the hydrophobicity imparted by the aliphatic chain at C-9,
      as well as a C-3,C-4 double bond, play crucial roles for inhibitory activity.
      Docking studies also suggested that hydrophobic interactions in the binding site,
      especially with Phe256 and Phe834, may be important for a strong inhibitory
      activity of the TCDs. In conclusion, a novel class of SERCA inhibitory compounds
      is presented. 

PMID- 25993620
TI  - Dynamic decoupling and local atomic order of a model multicomponent metallic
      glass-former.
AB  - The dynamics of multicomponent metallic alloys is spatially heterogeneous near
      glass transition. The diffusion coefficient of one component of the metallic
      alloys may also decouple from those of other components, i.e., the diffusion
      coefficient of each component depends differently on the viscosity of metallic
      alloys. In this work we investigate the dynamic heterogeneity and decoupling of a
      model system for multicomponent Pd43Cu27Ni10P20 melts by using a hard sphere
      model that considers the size disparity of alloys but does not take chemical
      effects into account. We also study how such dynamic behaviors would relate to
      the local atomic structure of metallic alloys. We find, from molecular dynamics
      simulations, that the smallest component P of multicomponent Pd43Cu27Ni10P20
      melts becomes dynamically heterogeneous at a translational relaxation time scale
      and that the largest major component Pd forms a slow subsystem, which has been
      considered mainly responsible for the stabilization of amorphous state of alloys.
      The heterogeneous dynamics of P atoms accounts for the breakdown of Stokes
      Einstein relation and also leads to the dynamic decoupling of P and Pd atoms. The
      dynamically heterogeneous P atoms decrease the lifetime of the local short-range
      atomic orders of both icosahedral and close-packed structures by orders of
      magnitude. 

PMID- 25993621
TI  - Correction: Characterization of course and terrain and their effect on skier
      speed in world cup alpine ski racing.

PMID- 25993622
TI  - [In Process Citation].

PMID- 25993623
TI  - Effect of high-voltage electrical stimulation on the albumin and histamine serum
      concentrations, edema, and pain in acute joint inflammation of rats.
AB  - BACKGROUND: The mechanism by which high-voltage electrical stimulation (HVPC)
      acts on edema reduction is unknown. OBJECTIVE: To assess the effect of HVPC with
      negative polarity (-) applied to the ankle of rats with acute joint inflammation.
      METHOD: Sixty-four rats were divided into four groups (n=16): inflamed+HVPC(-),
      0.03 mL application of iota-carrageenan (3%) to the tibiotarsal joint plus HVPC(
      ); inflamed+HVPC placebo, carrageenan application and HVPC placebo; normal+HVPC(
      ), HVPC application(-); and normal control, no intervention. The HVPC(-) 100 Hz
      at a submotor level was applied daily for 45 min on three consecutive days. The
      variables were pain, hind-foot volume, and serum histamine and albumin assessed
      before and during the 48 hours following inflammation. The variables were
      compared using the t test, one-way ANOVA, nested ANOVA for repeated measures, and
      the post hoc Bonferroni test. Analysis of covariance was applied to adjust the
      effects of HVPC(-) by measurements of pain, inflammation, albumin, and histamine
      at 24 h, and the final weight was compared to the other groups. The significance
      level was set at p<0.05. RESULTS: There were no differences between the
      inflamed+HVPC(-) and inflamed+HVPC placebo groups in terms of pain or edema
      (p>0.05). Albumin was reduced in the groups that received the intervention, but
      there was no differences between them. There was only a 24 hour increase in
      histamine with the normal+HVPC(-) (p=0.0001) and inflamed+HVPC placebo groups
      (p=0.01) compared to the normal control group. CONCLUSIONS: The results of the
      present study suggest that HVPC(-) with the parameters employed did not reduce
      pain or edema and did not change serum albumin or histamine levels,, which
      indicates the inability of this resource to have a positive effect when treating
      treat acute joint inflammation.

PMID- 25993624
TI  - Intra and inter-rater reliability study of pelvic floor muscle dynamometric
      measurements.
AB  - OBJECTIVE: The aim of this study was to evaluate the intra and inter-rater
      reliability of pelvic floor muscle (PFM) dynamometric measurements for maximum
      and average strengths, as well as endurance. METHOD: A convenience sample of 18
      nulliparous women, without any urogynecological complaints, aged between 19 and
      31 (mean age of 25.4 +/- 3.9) participated in this study. They were evaluated
      using a pelvic floor dynamometer based on load cell technology. The dynamometric
      evaluations were repeated in three successive sessions: two on the same day with
      a rest period of 30 minutes between them, and the third on the following day. All
      participants were evaluated twice in each session; first by examiner 1 followed
      by examiner 2. The vaginal dynamometry data were analyzed using three parameters:
      maximum strength, average strength, and endurance. The Intraclass Correlation
      Coefficient (ICC) was applied to estimate the PFM dynamometric measurement
      reliability, considering a good level as being above 0.75. RESULTS: The intra and
      inter-raters' analyses showed good reliability for maximum strength (ICC(intra
      rater1)=0.96, ICC(intra-rater2)=0.95, and ICC(inter-rater)=0.96), average
      strength (ICC(intra-rater1)=0.96, ICCi(ntra-rater2)=0.94, and ICC(inter
      rater)=0.97), and endurance (ICC(intra-rater1)=0.88, ICC(intra-rater2)=0.86, and
      ICC(inter-rater)=0.92) dynamometric measurements. CONCLUSIONS: The PFM
      dynamometric measurements showed good intra- and inter-rater reliability for
      maximum strength, average strength and endurance, which demonstrates that this is
      a reliable device that can be used in clinical practice.

PMID- 25993625
TI  - Lower limb ice application alters ground reaction force during gait initiation.
AB  - BACKGROUND: Cryotherapy is a widely used technique in physical therapy clinics
      and sports. However, the effects of cryotherapy on dynamic neuromuscular control
      are incompletely explained. OBJECTIVES: To evaluate the effects of cryotherapy
      applied to the calf, ankle and sole of the foot in healthy young adults on ground
      reaction forces during gait initiation. METHOD: This study evaluated the gait
      initiation forces, maximum propulsion, braking forces and impulses of 21 women
      volunteers through a force platform, which provided maximum and minimum ground
      reaction force values. To assess the effects of cooling, the task--gait
      initiation--was performed before ice application, immediately after and 30
      minutes after removal of the ice pack. Ice was randomly applied on separate days
      to the calf, ankle and sole of the foot of the participants. RESULTS: It was
      demonstrated that ice application for 30 minutes to the sole of the foot and calf
      resulted in significant changes in the vertical force variables, which returned
      to their pre-application values 30 minutes after the removal of the ice pack. Ice
      application to the ankle only reduced propulsion impulse. CONCLUSIONS: These
      results suggest that although caution is necessary when performing activities
      that require good gait control, the application of ice to the ankle, sole of the
      foot or calf in 30-minute intervals may be safe even preceding such activities.

PMID- 25993626
TI  - Reliability of different methodologies of infrared image analysis of myofascial
      trigger points in the upper trapezius muscle.
AB  - BACKGROUND: Infrared thermography is recognized as a viable method for evaluation
      of subjects with myofascial pain. OBJECTIVE: The aim of the present study was to
      assess the intra- and inter-rater reliability of infrared image analysis of
      myofascial trigger points in the upper trapezius muscle. METHOD: A reliability
      study was conducted with 24 volunteers of both genders (23 females) between 18
      and 30 years of age (22.12 +/- 2.54), all having cervical pain and presence of
      active myofascial trigger point in the upper trapezius muscle. Two trained
      examiners performed analysis of point, line, and area of the infrared images at
      two different periods with a 1-week interval. The intra-class correlation
      coefficient (ICC(2,1)) was used to assess the intra- and inter-rater reliability.
      RESULTS: With regard to the intra-rater reliability, ICC values were between
      0.591 and 0.993, with temperatures between 0.13 and 1.57  degrees C for values of
      standard error of measurement (SEM) and between 0.36 and 4.35  degrees C for the
      minimal detectable change (MDC). For the inter-rater reliability, ICC ranged from
      0.615 to 0.918, with temperatures between 0.43 and 1.22  degrees C for the SEM
      and between 1.19 and 3.38  degrees C for the MDC. CONCLUSION: The methods of
      infrared image analyses of myofascial trigger points in the upper trapezius
      muscle employed in the present study are suitable for clinical and research
      practices.

PMID- 25993627
TI  - Validation and reliability of a modified sphygmomanometer for the assessment of
      handgrip strength in Parkinson's disease.
AB  - BACKGROUND: Handgrip strength is currently considered a predictor of overall
      muscle strength and functional capacity. Therefore, it is important to find
      reliable and affordable instruments for this analysis, such as the modified
      sphygmomanometer test (MST). OBJECTIVES: To assess the concurrent criterion
      validity of the MST, to compare the MST with the Jamar dynamometer, and to
      analyze the reproducibility (i.e. reliability and agreement) of the MST in
      individuals with Parkinson's disease (PD). METHOD: The authors recruited 50
      subjects, 24 with PD (65.5 +/- 6.2 years of age) and 26 healthy elderly subjects
      (63.4 +/- 7.2 years of age). The handgrip strength was measured using the Jamar
      dynamometer and modified sphygmomanometer. The concurrent criterion validity was
      analyzed using Pearson's correlation coefficient and a simple linear regression
      test. The reproducibility of the MST was evaluated with the coefficient of intra
      class correlation (ICC(2,1)), the standard error of measurement (SEM), the
      minimal detectable change (MDC), and the Bland-Altman plot. For all of the
      analyses, alpha <= 0.05 was considered a risk. RESULTS: There was a significant
      correlation of moderate magnitude (r >= 0.45) between the MST and the Jamar
      dynamometer. The MST had excellent reliability (ICC(2,1) >= 0.7). The SEM and the
      MDC were adequate; however, the Bland-Altman plot indicated an unsatisfactory
      interrater agreement. CONCLUSIONS: The MST exhibited adequate validity and
      excellent reliability and is, therefore, suitable for monitoring the handgrip
      strength in PD. However, if the goal is to compare the measurements between
      examiners, the authors recommend that the data be interpreted with caution.

PMID- 25993628
TI  - Balance, gait, functionality and strength: comparison between elderly fallers and
      non-fallers.
AB  - BACKGROUND: Accidental falls are a major health problem related to aging and
      affect one in every three elderly individuals over the age of sixty. OBJECTIVE:
      To evaluate and compare the muscle strength, gait kinematics parameters, and
      performance in functional tests between elderly subjects with and without a prior
      history of falls. In addition, the association between the history of falls and
      the variables that demonstrated differences between groups were tested. METHOD:
      62 elderly subjects participated in the study and were allocated to the group
      with falls history (FG; n=20; 68.0 +/- 6.9 years old) or the group without falls
      history (CG; n=42; 65.5 +/- 4.1 years old). Maximal strength, gait kinematics
      parameters, and functional tests were tested. RESULTS: The FG showed lower muscle
      strength in the knee flexors (51.45 +/- 8.6 vs. 62.09 +/- 19 Kg), lower average
      toe clearance during the swing phase (0.04 +/- 0.006 vs. 0.043 +/- 0.005 m), and
      lower performance in the "8-foot up-and-go" test (5.3 +/- 0.7 vs. 5.8 +/- 0.7 s)
      (p<0.05). There were no associations between any variables and falls, but the
      increased time in the "8-foot up-and-go" test may double the likelihood of a fall
      occurring. CONCLUSION: Fallers have reduced lower limb strength, gait
      alterations, the worst performance in the dynamic balance test, and an increased
      risk of falls.

PMID- 25993629
TI  - The relationship between dual-task and cognitive performance among elderly
      participants who exercise regularly.
AB  - BACKGROUND: The dual-task performance is associated with the functionality of the
      elderly and it becomes more complex with age. OBJECTIVE: To investigate the
      relationship between the Timed Up and Go dual task (TUG-DT) and cognitive tests
      among elderly participants who exercise regularly. METHOD: This study examined 98
      non-institutionalized people over 60 years old who exercised regularly.
      Participants were assessed using the TUG-DT (i.e. doing the TUG while listing the
      days of the week in reverse order), the Montreal Cognitive Assessment (MoCA), the
      Clock Drawing Test (CDT), and the Mini Mental State Examination (MMSE). The motor
      (i.e. time and number of steps) and cognitive (i.e. number of correct words) data
      were collected from TUG-DT. We used a significance level of alpha=0.05 and SPSS
      17.0 for all data analyses. RESULTS: This current elderly sample featured a
      predominance of women (69.4%) who were highly educated (median=10 years of
      education) compared to Brazilian population and mostly non-fallers (86.7%). The
      volunteers showed a good performance on the TUG-DT and the other cognitive tests,
      except the MoCA, with scores below the cutoff of 26 points. Significant and weak
      correlations were observed between the TUG-DT (time) and the visuo
      spatial/executive domain of the MoCA and the MMSE. The cognitive component of the
      TUG-DT showed strong correlations between the total MoCA performance score and
      its visuo-spatial/executive domain. CONCLUSIONS: The use of the TUG-DT to assess
      cognition is promising; however, the use of more challenging cognitive tasks
      should be considered when the study population has a high level of education.

PMID- 25993631
TI  - Rapid changes of body weight after a headstand: a metrological analysis.
AB  - Despite recent rules from amateur wrestling sport-governing bodies intended to
      discourage extreme weight loss measures, wrestling culture still includes varied
      methods to make weight, including holding a headstand position immediately before
      stepping on the scale. The procedure, according to the notion, will reduce
      reported mass anywhere between 250 and 500 g (weight between 2.45 and 4.89 N).
      The aim of this study was to compare any possible differences between the
      headstand procedure (HS) and a normal (CON) weight measure, using a metrological
      approach defined by the European Association of National Metrology Institutes.
      Seventeen adult men were weighed on a force plate before and after doing a
      headstand or standing normally for 30s. The order of treatment application was
      assigned randomly. Post-test weight was significantly larger than pre-test (mean
      +/- s.d.) (640.7 +/- 62.8 N and 640.3 +/- 62.7 N, respectively, p < 0.0001) under
      both treatments. No treatment vs. time of test interaction was found. No
      significant difference was found between CON and HS weight (640.6 +/- 62.8 N and
      640.9 +/- 62.9 N, respectively, p=0.3815). The metrological tests suggest that
      the statistical differences found are related to the force plate measuring errors
      in every pre-established time interval. The 45 g (0.44 N) difference found
      between pretest and post-test lies within the uncertainty range identified for
      the equipment (+/- 110 g or 1.08 N). In conclusion, a 30-second headstand has no
      significant effect on registered body weight. The small variations obtained were
      due to equipment-associated measuring errors. This experiment offers systematic
      empirical evidence to aid in the elimination of this unjustified practice among
      the wrestling community.

PMID- 25993630
TI  - L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial
      Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.
AB  - OBJECTIVE: To study the effects of L-arginine (L-Arg) on total body aerobic
      capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance
      Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy
      with Lactic Acidosis and Stroke-like episodes) syndrome. METHODS: We performed a
      case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene)
      with different % blood mutant mtDNA to evaluate total body maximal aerobic
      capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P
      MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of
      these parameters to single dose and a 6-week steady-state trial of oral L
      Arginine. RESULTS: At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001).
      On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr)
      (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p =
      0.0002) when compared to matched controls. With L-arginine therapy, the following
      trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean %
      maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at
      AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were
      noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase
      in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time
      of PCr recovery (marker of mitochondrial activity) following 5 minutes of
      moderate intensity exercise (4) increase in torque. SIGNIFICANCE: These results
      suggest an improvement in aerobic capacity and muscle metabolism in MELAS
      subjects in response to supplementation with L-Arg. Intramyocellular
      hypomagnesemia is a novel finding that warrants further study. CLASSIFICATION OF
      EVIDENCE: Class III evidence that L-arginine improves aerobic capacity and muscle
      metabolism in MELAS subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01603446.

PMID- 25993632
TI  - Association between Stress Response Genes and Features of Diurnal Cortisol Curves
      in the Multi-Ethnic Study of Atherosclerosis: A New Multi-Phenotype Approach for
      Gene-Based Association Tests.
AB  - The hormone cortisol is likely to be a key mediator of the stress response that
      influences multiple physiologic systems that are involved in common chronic
      disease, including the cardiovascular system, the immune system, and metabolism.
      In this paper, a candidate gene approach was used to investigate genetic
      contributions to variability in multiple correlated features of the daily
      cortisol profile in a sample of European Americans, African Americans, and
      Hispanic Americans from the Multi-Ethnic Study of Atherosclerosis (MESA). We
      proposed and applied a new gene-level multiple-phenotype analysis and carried out
      a meta-analysis to combine the ethnicity specific results. This new analysis,
      instead of a more routine single marker-single phenotype approach identified a
      significant association between one gene (ADRB2) and cortisol features (meta
      analysis p-value=0.0025), which was not identified by three other commonly used
      existing analytic strategies: 1. Single marker association tests involving each
      single cortisol feature separately; 2. Single marker association tests jointly
      testing for multiple cortisol features; 3. Gene-level association tests
      separately carried out for each single cortisol feature. The analytic strategies
      presented consider different hypotheses regarding genotype-phenotype association
      and imply different costs of multiple testing. The proposed gene-level analysis
      integrating multiple cortisol features across multiple ethnic groups provides new
      insights into the gene-cortisol association. 

PMID- 25993633
TI  - Chikungunya virus transmission potential by local Aedes mosquitoes in the
      Americas and Europe.
AB  - BACKGROUND: Chikungunya virus (CHIKV), mainly transmitted in urban areas by the
      mosquitoes Aedes aegypti and Aedes albopictus, constitutes a major public health
      problem. In late 2013, CHIKV emerged on Saint-Martin Island in the Caribbean and
      spread throughout the region reaching more than 40 countries. Thus far, Ae.
      aegypti mosquitoes have been implicated as the sole vector in the outbreaks,
      leading to the hypothesis that CHIKV spread could be limited only to regions
      where this mosquito species is dominant. METHODOLOGY/PRINCIPAL FINDINGS: We
      determined the ability of local populations of Ae. aegypti and Ae. albopictus
      from the Americas and Europe to transmit the CHIKV strain of the Asian genotype
      isolated from Saint-Martin Island (CHIKV_SM) during the recent epidemic, and an
      East-Central-South African (ECSA) genotype CHIKV strain isolated from La Reunion
      Island (CHIKV_LR) as a well-characterized control virus. We also evaluated the
      effect of temperature on transmission of CHIKV_SM by European Ae. albopictus. We
      found that (i) Aedes aegypti from Saint-Martin Island transmit CHIKV_SM and
      CHIKV_LR with similar efficiency, (ii) Ae. aegypti from the Americas display
      similar transmission efficiency for CHIKV_SM, (iii) American and European
      populations of the alternative vector species Ae. albopictus were as competent as
      Ae. aegypti populations with respect to transmission of CHIKV_SM and (iv)
      exposure of European Ae. albopictus to low temperatures (20 degrees C)
      significantly reduced the transmission potential for CHIKV_SM.
      CONCLUSIONS/SIGNIFICANCE: CHIKV strains belonging to the ECSA genotype could also
      have initiated local transmission in the new world. Additionally, the ongoing
      CHIKV outbreak in the Americas could potentially spread throughout Ae. aegypti-
      and Ae. albopictus-infested regions of the Americas with possible imported cases
      of CHIKV to Ae. albopictus-infested regions in Europe. Colder temperatures may
      decrease the local transmission of CHIKV_SM by European Ae. albopictus,
      potentially explaining the lack of autochthonous transmission of CHIKV_SM in
      Europe despite the hundreds of imported CHIKV cases returning from the Caribbean.

PMID- 25993634
TI  - Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by
      Flavonoids and Substrates of Cyclic Amidohydrolases.
AB  - Dihydropyrimidinase is a member of the cyclic amidohydrolase family, which also
      includes allantoinase, dihydroorotase, hydantoinase, and imidase. These
      metalloenzymes possess very similar active sites and may use a similar mechanism
      for catalysis. However, whether the substrates and inhibitors of other cyclic
      amidohydrolases can inhibit dihydropyrimidinase remains unclear. This study
      investigated the inhibition of dihydropyrimidinase by flavonoids and substrates
      of other cyclic amidohydrolases. Allantoin, dihydroorotate, 5-hydantoin acetic
      acid, acetohydroxamate, orotic acid, and 3-amino-1,2,4-triazole could slightly
      inhibit dihydropyrimidinase, and the IC50 values of these compounds were within
      the millimolar range. The inhibition of dihydropyrimidinase by flavonoids, such
      as myricetin, quercetin, kaempferol, galangin, dihydromyricetin, and myricitrin,
      was also investigated. Some of these compounds are known as inhibitors of
      allantoinase and dihydroorotase. Although the inhibitory effects of these
      flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin
      significantly inhibited dihydropyrimidinase with IC50 values of 48 and 40 MUM for
      the substrates dihydrouracil and 5-propyl-hydantoin, respectively. The results
      from the Lineweaver-Burk plot indicated that dihydromyricetin was a competitive
      inhibitor. Results from fluorescence quenching analysis indicated that
      dihydromyricetin could form a stable complex with dihydropyrimidinase with the
      K(d) value of 22.6 MUM. A structural study using PatchDock showed that
      dihydromyricetin was docked in the active site pocket of dihydropyrimidinase,
      which was consistent with the findings from kinetic and fluorescence studies.
      This study was the first to demonstrate that naturally occurring product
      dihydromyricetin inhibited dihydropyrimidinase, even more than the substrate
      analogs (>3 orders of magnitude). These flavonols, particularly myricetin, may
      serve as drug leads and dirty drugs (for multiple targets) for designing
      compounds that target several cyclic amidohydrolases.

PMID- 25993635
TI  - The Trends in Excess Mortality in Winter vs. Summer in a Sub-Tropical City and
      Its Association with Extreme Climate Conditions.
AB  - While there is literature on excess winter mortality, there are few studies
      examining the evolution of its trend which may be changing in parallel with
      global warming. This study aimed to examine the trend in the excess mortality in
      winter as compared to summer among the older population in a sub-tropical city
      and to explore its association with extreme weather. We used a retrospective
      study based on the registered deaths among the older population in Hong Kong
      during 1976-2010. An Excess Mortality for Winter versus Summer (EMWS) Index was
      used to quantify the excess number of deaths in winter compared to summer.
      Multiple linear regressions were used to analyze the trends and its association
      with extreme weather. Overall, the EMWS Index for ischemic heart disease,
      cerebrovascular diseases, chronic lower respiratory diseases, pneumonia, and
      other causes were 43.0%, 34.2%, 42.7%, 23.4% and 17.6%, respectively. Significant
      decline was observed in the EMWS Index for chronic lower respiratory diseases and
      other causes. The trend in the index for cerebrovascular diseases depended on the
      age group, with older groups showing a decline but younger groups not showing any
      trend. Meteorological variables, in terms of extreme weather, were associated
      with the trends in the EMWS Index. We concluded that shrinking excess winter
      mortality from cerebrovascular diseases and chronic lower respiratory diseases
      was found in a sub-tropical city. These trends were associated with extreme
      weather, which coincided with global warming. 

PMID- 25993636
TI  - Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down
      Referred from a District Hospital to Primary Health Clinics in Rural South
      Africa.
AB  - BACKGROUND: HIV and tuberculosis (TB) coinfection remains a major public health
      threat in sub-Saharan Africa. Integration and decentralization of HIV and TB
      treatment services are being implemented, but data on outcomes of this strategy
      are lacking in rural, resource-limited settings. We evaluated TB treatment
      outcomes in TB/HIV coinfected patients in an integrated and decentralized system
      in rural KwaZulu-Natal, South Africa. METHODS: We retrospectively studied a
      cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB
      at a district hospital HIV clinic from January 2012-June 2013. Patients were
      eligible for down-referral to primary health clinics(PHCs) for TB treatment
      completion if they met specific clinical criteria. Records were reviewed for
      patients' demographic, baseline clinical and laboratory information, past HIV and
      TB history, and TB treatment outcomes. RESULTS: Of 657(88.7%) patients,
      322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had
      pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from
      the district level HIV clinic to PHCs for treatment completion; 377(57.4%)
      remained at the district hospital. Retained patients possessed characteristics
      indicative of more severe disease. In total, 540(82.2%) patients experienced
      treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients
      experienced higher treatment success, and lower mortality, but were more likely
      to default, primarily at the time of transfer to PHC. CONCLUSION:
      Decentralization of TB treatment to the primary care level is feasible in rural
      South Africa. Treatment outcomes are favorable when patients are carefully chosen
      for down-referral. Higher mortality in retained patients reflects increased
      baseline disease severity while higher default among down-referred patients
      reflects failed linkage of care. Better linkage mechanisms are needed including
      improved identification of potential defaulters, increased patient education,
      active communication between hospitals and PHCs, and tracing of patients lost to
      follow up. Decentralized and integrated care is successful for carefully selected
      TB/HIV coinfected patients and should be expanded.

PMID- 25993637
TI  - NEMS With Broken T Symmetry: Graphene Based Unidirectional Acoustic Transmission
      Lines.
AB  - In this work we discuss the idea of one-way acoustic signal isolation in low
      dimensional nanoelectromechanical oscillators. We report a theoretical study
      showing that one-way conversion between in-phase and anti-phase vibrational modes
      of a double layer graphene nanoribbon is achieved by introducing spatio-temporal
      modulation of system properties. The required modulation length in order to reach
      full conversion between the two modes is subsequently calculated. Generalization
      of the method beyond graphene nanoribbons and realization of a NEMS signal
      isolator are also discussed. 

PMID- 25993638
TI  - Increased Cardiovascular Mortality in Subjects With Metabolic Syndrome Is Largely
      Attributable to Diabetes and Hypertension in 159,971 Korean Adults.
AB  - CONTEXT: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease
      (CVD) mortality. OBJECTIVE: This study aimed to evaluate the association of MetS
      with all-cause and cardiovascular mortality in apparently healthy young Korean
      subjects. DESIGN: A retrospective study of 155,971 participants (mean age, 41.8
      y) in a health screening program, followed up for 3.7 years (597,628.2 person
      years). The risk for all-cause mortality and CVD mortality were analyzed
      according to the presence or absence of MetS. MAIN OUTCOMES: A total of 542
      subjects died during followup. Women with MetS showed a significantly increased
      age-adjusted hazard ratio (HR) for all-cause mortality compared with women
      without MetS, even after adjustment for confounding factors (HR, 1.82; 95%
      confidence interval [CI], 1.15-2.88). Subjects with MetS showed a significantly
      increased risk for CVD mortality compared with those without MetS, even after
      adjustment for confounding factors (HR, 1.60; 95% CI, 1.02-2.20), of which
      significance disappeared when subjects with diabetes or hypertension at baseline
      were excluded from the analysis (HR, 0.95; 95% CI, 0.29-3.12). CONCLUSIONS: The
      presence of MetS increased the risk for all-cause mortality in women and the risk
      for CVD mortality in total population. These increased HR attributed to the pre
      existing diabetes or hypertension in this population.

PMID- 25993639
TI  - Cinacalcet Treatment in an Adolescent With Concurrent 22q11.2 Deletion Syndrome
      and Familial Hypocalciuric Hypercalcemia Type 3 Caused by AP2S1 Mutation.
AB  - CONTEXT: The 22q11.2 deletion syndrome (DS) is a common multiple anomaly syndrome
      in which typical features include congenital heart defects, facial dysmorphism,
      and palatal anomalies. Hypocalcemia due to hypoparathyroidism is a common
      endocrine manifestation resulting from variable parathyroid hypoplasia, but
      hypercalcemia has not previously been reported in 22q11.2 DS. CASE DESCRIPTION:
      Our patient is a 16-year-old adolescent male with dysmorphic facial features and
      delayed motor and speech development. At 2 years of age, 22q11.2 DS was confirmed
      by fluorescence in situ hybridization. In contrast to hypoparathyroidism that is
      usually seen in 22q11.2 DS, this patient had early childhood-onset hypercalcemia
      with inappropriately high PTH levels and hypocalciuria. Genomic DNA was obtained
      from the proband and screened for calcium-sensing receptor (CASR) mutations with
      negative results. No parathyroid tissue could be localized by imaging or surgical
      exploration. As a result of symptomatic hypercalcemia, the patient was treated
      with a calcimimetic (cinacalcet). During the treatment, plasma calcium normalized
      with mild symptoms of hypocalcemia. After discontinuation of cinacalcet, calcium
      returned to high pretreatment levels. Further DNA analysis of adaptor protein-2
      sigma subunit (AP2S1) showed a heterozygous missense mutation c.44 G>T, resulting
      in a p.R15L substitution; the mutation was absent in the healthy parents and two
      siblings. CONCLUSIONS: Hypercalcemia in our patient with 22q11.2 DS could be
      explained by the de novo mutation in AP2S1. Identification of a genetic cause for
      hypercalcemia is helpful in guiding management and avoiding unnecessary
      treatment.

PMID- 25993641
TI  - Fetal Sex and the Natural History of Maternal Risk of Diabetes During and After
      Pregnancy.
AB  - CONTEXT: It has recently emerged that carrying a male fetus is associated with
      poorer maternal beta-cell function in pregnancy and an increased risk of
      gestational diabetes mellitus (GDM). beta-cell dysfunction is the central
      pathophysiologic defect underlying both GDM and subsequent postpartum progression
      to type 2 diabetes mellitus (T2DM). OBJECTIVE: This was a retrospective cohort
      study that aimed to determine whether fetal sex influences the natural history of
      maternal risk of diabetes after delivery and in a subsequent pregnancy. SETTING:
      The study was conducted using population-based administrative databases in
      Ontario, Canada. PATIENTS: All women with a singleton live-birth first pregnancy
      between April 2000 and March 2010 (n = 642 987) were included. EXPOSURE: Fetal
      sex was the exposure of interest (313 280 delivered a girl; 329 707 delivered a
      boy). MAIN OUTCOME MEASURE: Development of T2DM or a second pregnancy were the
      main outcome measures. Glucose tolerance in each pregnancy was classified as
      either GDM or non-GDM. RESULTS: The population was followed for a median of 3.8
      years. Carrying a boy yielded a higher risk of GDM in both the first pregnancy
      (odds ratio [OR] =1.03; 95% confidence interval [CI], 1.0002-1.054) and second
      pregnancy (OR =1.04, 95% CI, 1.01-1.08). For women with GDM in the first
      pregnancy, the likelihood of developing T2DM before a second pregnancy was higher
      if they delivered a girl (OR = 1.07; 95% CI, 1.01-1.12). Recurrence of GDM was
      not affected by fetal sex (P = .7). However, among women with a non-GDM first
      pregnancy while carrying a girl, having a boy in their second pregnancy predicted
      an increased risk of GDM (OR = 1.07, 95% CI, 1.01-1.14). CONCLUSIONS: Fetal sex
      is a previously unrecognized factor that is associated with maternal diabetic
      risk both after delivery and in a subsequent pregnancy.

PMID- 25993640
TI  - Association of Exposure to Di-2-Ethylhexylphthalate Replacements With Increased
      Insulin Resistance in Adolescents From NHANES 2009-2012.
AB  - CONTEXT: Di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP) are
      environmental chemicals increasingly used to replace di-2-ethylhexylphthalate
      (DEHP) and commonly found in processed foods. Phthalate exposures, in particular
      DEHP, have been associated with insulin resistance in adolescents, but there are
      no data regarding the two substitutes, DINP and DIDP. OBJECTIVE: This study aimed
      to examine associations of DINP, DIDP, and DEHP with insulin resistance outcomes.
      DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional analysis of 2009
      2012 National Health and Nutrition Examination Surveys (NHANES) composed of 356
      fasting 12-19-year-olds. MAIN OUTCOME MEASURES: Insulin resistance as a
      categorical outcome expressed as homeostatic model assessment of insulin
      resistance (HOMA-IR), using a cut point of 4.39 to define insulin resistance. We
      also examined continuous HOMA-IR as an outcome in secondary analyses. RESULTS:
      Controlling for demographic and behavioral factors, diet, age, body mass index,
      and urinary creatinine, for each log increase in DINP metabolite, a 0.08 (P =
      .001) increase in HOMA-IR was identified. Compared with the first tertile of DINP
      (23.4% adjusted prevalence), the third tertile was associated with a 34.4%
      prevalence (95% confidence interval [CI], 27.3-41.6%; P = .033) of insulin
      resistance. Similarly, compared with the first tertile of DEHP (20.5% adjusted
      prevalence), the third tertile had 37.7% prevalence (95% CI 29.8-45.6%; P =
      .003). CONCLUSIONS: Urinary DINP concentrations were associated with increased
      insulin resistance in this cross-sectional study of adolescents. The previously
      identified association of DEHP with insulin resistance was also confirmed.
      Further, longitudinal studies are needed to confirm these associations, with the
      possibility to assess opportunities for intervention.

PMID- 25993642
TI  - Neonicotinoid-Coated Zea mays Seeds Indirectly Affect Honeybee Performance and
      Pathogen Susceptibility in Field Trials.
AB  - Thirty-two honeybee (Apis mellifera) colonies were studied in order to detect and
      measure potential in vivo effects of neonicotinoid pesticides used in cornfields
      (Zea mays spp) on honeybee health. Honeybee colonies were randomly split on four
      different agricultural cornfield areas located near Quebec City, Canada. Two
      locations contained cornfields treated with a seed-coated systemic neonicotinoid
      insecticide while the two others were organic cornfields used as control
      treatments. Hives were extensively monitored for their performance and health
      traits over a period of two years. Honeybee viruses (brood queen cell virus BQCV,
      deformed wing virus DWV, and Israeli acute paralysis virus IAPV) and the brain
      specific expression of a biomarker of host physiological stress, the
      Acetylcholinesterase gene AChE, were investigated using RT-qPCR. Liquid
      chromatography-mass spectrometry (LC-MS) was performed to detect pesticide
      residues in adult bees, honey, pollen, and corn flowers collected from the
      studied hives in each location. In addition, general hive conditions were
      assessed by monitoring colony weight and brood development. Neonicotinoids were
      only identified in corn flowers at low concentrations. However, honeybee colonies
      located in neonicotinoid treated cornfields expressed significantly higher
      pathogen infection than those located in untreated cornfields. AChE levels showed
      elevated levels among honeybees that collected corn pollen from treated fields.
      Positive correlations were recorded between pathogens and the treated locations.
      Our data suggests that neonicotinoids indirectly weaken honeybee health by
      inducing physiological stress and increasing pathogen loads. 

PMID- 25993643
TI  - Novel Features of the Prenatal Horn Bud Development in Cattle (Bos taurus).
AB  - Whereas the genetic background of horn growth in cattle has been studied
      extensively, little is known about the morphological changes in the developing
      fetal horn bud. In this study we histologically analyzed the development of horn
      buds of bovine fetuses between ~70 and ~268 days of pregnancy and compared them
      with biopsies taken from the frontal skin of the same fetuses. In addition we
      compared the samples from the wild type (horned) fetuses with samples taken from
      the horn bud region of age-matched genetically hornless (polled) fetuses. In
      summary, the horn bud with multiple layers of vacuolated keratinocytes is
      histologically visible early in fetal life already at around day 70 of gestation
      and can be easily differentiated from the much thinner epidermis of the frontal
      skin. However, at the gestation day (gd) 212 the epidermis above the horn bud
      shows a similar morphology to the epidermis of the frontal skin and the
      outstanding layers of vacuolated keratinocytes have disappeared. Immature hair
      follicles are seen in the frontal skin at gd 115 whereas hair follicles below the
      horn bud are not present until gd 155. Interestingly, thick nerve bundles appear
      in the dermis below the horn bud at gd 115. These nerve fibers grow in size over
      time and are prominent shortly before birth. Prominent nerve bundles are not
      present in the frontal skin of wild type or in polled fetuses at any time,
      indicating that the horn bud is a very sensitive area. The samples from the horn
      bud region from polled fetuses are histologically equivalent to samples taken
      from the frontal skin in horned species. This is the first study that presents
      unique histological data on bovine prenatal horn bud differentiation at different
      developmental stages which creates knowledge for a better understanding of recent
      molecular findings. 

PMID- 25993644
TI  - Modeling and predicting tissue movement and deformation for high intensity
      focused ultrasound therapy.
AB  - PURPOSE: In ultrasound-guided High Intensity Focused Ultrasound (HIFU) therapy,
      the target tissue (such as a tumor) often moves and/or deforms in response to an
      external force. This problem creates difficulties in treating patients and can
      lead to the destruction of normal tissue. In order to solve this problem, we
      present a novel method to model and predict the movement and deformation of the
      target tissue during ultrasound-guided HIFU therapy. METHODS: Our method
      computationally predicts the position of the target tissue under external force.
      This prediction allows appropriate adjustments in the focal region during the
      application of HIFU so that the treatment head is kept aligned with the diseased
      tissue through the course of therapy. To accomplish this goal, we utilize the cow
      tissue as the experimental target tissue to collect spatial sequences of
      ultrasound images using the HIFU equipment. A Geodesic Localized Chan-Vese (GLCV)
      model is developed to segment the target tissue images. A 3D target tissue model
      is built based on the segmented results. A versatile particle framework is
      constructed based on Smoothed Particle Hydrodynamics (SPH) to model the movement
      and deformation of the target tissue. Further, an iterative parameter estimation
      algorithm is utilized to determine the essential parameters of the versatile
      particle framework. Finally, the versatile particle framework with the determined
      parameters is used to estimate the movement and deformation of the target tissue.
      RESULTS: To validate our method, we compare the predicted contours with the
      ground truth contours. We found that the lowest, highest and average Dice
      Similarity Coefficient (DSC) values between predicted and ground truth contours
      were, respectively, 0.9615, 0.9770 and 0.9697. CONCLUSION: Our experimental
      result indicates that the proposed method can effectively predict the dynamic
      contours of the moving and deforming tissue during ultrasound-guided HIFU
      therapy.

PMID- 25993645
TI  - Common magnitude representation of fractions and decimals is task dependent.
AB  - Although several studies have compared the representation of fractions and
      decimals, no study has investigated whether fractions and decimals, as two types
      of rational numbers, share a common representation of magnitude. The current
      study aimed to answer the question of whether fractions and decimals share a
      common representation of magnitude and whether the answer is influenced by task
      paradigms. We included two different number pairs, which were presented
      sequentially: fraction-decimal mixed pairs and decimal-fraction mixed pairs in
      all four experiments. Results showed that when the mixed pairs were very close
      numerically with the distance 0.1 or 0.3, there was a significant distance effect
      in the comparison task but not in the matching task. However, when the mixed
      pairs were further apart numerically with the distance 0.3 or 1.3, the distance
      effect appeared in the matching task regardless of the specific stimuli. We
      conclude that magnitudes of fractions and decimals can be represented in a common
      manner, but how they are represented is dependent on the given task. Fractions
      and decimals could be translated into a common representation of magnitude in the
      numerical comparison task. In the numerical matching task, fractions and decimals
      also shared a common representation. However, both of them were represented
      coarsely, leading to a weak distance effect. Specifically, fractions and decimals
      produced a significant distance effect only when the numerical distance was
      larger. 

PMID- 25993647
TI  - The role of the shape resonance state in low energy electron induced single
      strand break in 2'-deoxycytidine-5'-monophosphate.
AB  - Low energy electron (LEE) induced single strand break (SSB) has been studied for
      2'-deoxycytidine-5'-monophosphate (5'-dCMPH) molecules in the gas phase by means
      of ab initio electronic structure methods and local complex potential based time
      dependent wavepacket quantum mechanical calculations. We have found that the LEE
      attachment to this cytidine nucleotide results in the formation of a transient
      metastable anion. The results obtained here show that the electron attachment
      takes place at the cytosine nucleobase center and within 18-20 fs, the LEE
      transfers to the sigma* orbital of the sugar-phosphate 5' C-O bond. The
      characteristic electron attachment cross section spectrum is found at ~1 eV,
      which is in good agreement with the available experimental observations. Quantum
      mechanical tunneling of the 5' C-O bound vibrational energy levels may contribute
      to SSB only above 1.5 eV energy regimes. 

PMID- 25993646
TI  - Efficacy and Safety of HER2-Targeted Agents for Breast Cancer with HER2
      Overexpression: A Network Meta-Analysis.
AB  - BACKGROUND: Clinical trials of human epidermal growth factor receptor 2 (HER2)
      targeted agents added to standard treatment have been efficacious for HER2
      positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has
      evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and
      pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We
      performed a network meta-analysis of both direct and indirect comparisons to
      evaluate the effect of adding HER2-targeted agents to standard treatment and
      examined side effects. METHODS: We performed a Bayesian-framework network meta
      analysis of randomized controlled trials to compare 6 HER2-targeted treatment
      regimens and 1 naive standard treatment (NST, without any-targeted drugs) in
      targeted treatment of HER2+ breast cancer in adults. These treatment regimens
      were T-DM1, LC (lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib
      and trastuzumab), and PEHC (pertuzumab and trastuzumab). The main outcomes were
      overall survival and response rates. We also examined side effects of rash, LVEF
      (left ventricular ejection fraction), fatigue, and gastrointestinal disorders,
      and performed subgroup analysis for the different treatment regimens in
      metastatic or advanced breast cancer. RESULTS: We identified 25 articles of 21
      trials, with data for 11,276 participants. T-DM1 and PEHC were more efficient
      drug regimens with regard to overall survival as compared with LHC, LC, HC and
      PEC. The incidence of treatment-related rash occurs more frequently in the
      patients who received LC treatment regimen than PEHC and T-DM1 and HC. In
      subgroup analysis, T-DM1 was associated with increased overall survival as
      compared with LC and HC. PEHC was associated with increased overall response as
      compared with LC, HC, and NST. CONCLUSIONS: Overall, the regimen of T-DM1 as well
      as pertuzumab in combination with trastuzumab and docetaxel is efficacious with
      fewer side effects as compared with other regimens, especially for advanced HER2+
      breast cancer. IMPACT: This study suggests that both T-DM1 and PEHC therapy are
      potentially and equally useful treatments for HER2+ breast cancer.

PMID- 25993648
TI  - Peroral endoscopic myotomy can improve esophageal motility in patients with
      achalasia from a large sample self-control research (66 patients).
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) as a new approach to achalasia
      attracts broad attention. The primary objective of this study was to evaluate the
      results with esophageal motility after POEM through the first large sample
      clinical research. PATIENTS AND METHODS: We have a self-control research with all
      patients (205 in total) who underwent POEM from 2010 to 2014 at our Digestive
      Endoscopic Center, 66 patients of which underwent high resolution manometry (HRM)
      before and after POEM in our motility laboratory. Follow-ups last for 5.6 months
      on average. Outcome variables analyzed included upper esophageal sphincter
      pressure (UESP), upper esophageal sphincter residual pressure (UESRP), lower
      esophageal sphincter pressure (LESP), lower esophageal sphincter residual
      pressure (LESRP) and esophageal body peristalsis. We have a statistical analysis
      to illustrate how POEM impacts on the change of esophageal motility. RESULTS: The
      symptoms related to dysphagia were relieved in 95% of patients in recent term
      after POEM. While HRM showed a statistically significant reduction of URSRP, LESP
      and LESRP (P<0.01), however, peristalsis was not consistently affected. There
      were 11 patients who had undergone other prior endoscopic treatment (endoscopic
      dilation or botulinum toxin injection) and 55 patients had not. The statistical
      difference (P>0.05) did not occur for these two groups on LESP and LESRP
      reduction. CONCLUSIONS: POEM clearly relieved the symptoms related to dysphagia
      by lowering the pressure of upper esophageal sphincter (UES) and lower esophageal
      sphincter (LES),and other endoscopic treatment before POEM did not affect the
      improvement of LES pressure. These results are concluded from our short-term
      follow-up study, while the long-term efficacy remains to be further illustrated.
      TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-TRC-12002204).

PMID- 25993649
TI  - Transcripts and MicroRNAs Responding to Salt Stress in Musa acuminata Colla (AAA
      Group) cv. Berangan Roots.
AB  - Physiological responses to stress are controlled by expression of a large number
      of genes, many of which are regulated by microRNAs. Since most banana cultivars
      are salt-sensitive, improved understanding of genetic regulation of salt induced
      stress responses in banana can support future crop management and improvement in
      the face of increasing soil salinity related to irrigation and climate change. In
      this study we focused on determining miRNA and their targets that respond to NaCl
      exposure and used transcriptome sequencing of RNA and small RNA from control and
      NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome
      and identify orthologous and Musa-specific miRNA responding to salinity. We
      observed that, banana roots responded to salinity stress with changes in
      expression for a large number of genes (9.5% of 31,390 expressed unigenes) and
      reduction in levels of many miRNA, including several novel miRNA and banana
      specific miRNA-target pairs. Banana roots expressed a unique set of orthologous
      and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent
      manner. Gene expression patterns of miRNA compared with those of their predicted
      mRNA targets indicated that a majority of the differentially expressed miRNAs
      were down-regulated in response to increased salinity, allowing increased
      expression of targets involved in diverse biological processes including stress
      signaling, stress defence, transport, cellular homeostasis, metabolism and other
      stress-related functions. This study may contribute to the understanding of gene
      regulation and abiotic stress response of roots and the high-throughput
      sequencing data sets generated may serve as important resources related to salt
      tolerance traits for functional genomic studies and genetic improvement in
      banana. 

PMID- 25993651
TI  - Isolation of murine peritoneal macrophages to carry out gene expression analysis
      upon Toll-like receptors stimulation.
AB  - During infection and inflammation, circulating monocytes leave the bloodstream
      and migrate into tissues, where they differentiate into macrophages. Macrophages
      express surface Toll-like receptors (TLRs), which recognize molecular patterns
      conserved through evolution in a wide range of microorganisms. TLRs play a
      central role in macrophage activation which is usually associated with gene
      expression alteration. Macrophages are critical in many diseases and have emerged
      as attractive targets for therapy. In the following protocol, we describe a
      procedure to isolate murine peritoneal macrophages using Brewer's thioglycollate
      medium. The latter will boost monocyte migration into the peritoneum, accordingly
      this will raise macrophage yield by 10-fold. Several studies have been carried
      out using bone marrow, spleen or peritoneal derived macrophages. However,
      peritoneal macrophages were shown to be more mature upon isolation and are more
      stable in their functionality and phenotype. Thus, macrophages isolated from
      murine peritoneal cavity present an important cell population that can serve in
      different immunological and metabolic studies. Once isolated, macrophages were
      stimulated with different TLR ligands and consequently gene expression was
      evaluated. 

PMID- 25993652
TI  - S100A9: A Potential Biomarker for the Progression of Non-Alcoholic Fatty Liver
      Disease and the Diagnosis of Non-Alcoholic Steatohepatitis.
AB  - Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic
      steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However,
      NASH and T2DM do not always develop coordinately. Additionally, there are no
      definite noninvasive methods for NASH diagnosis currently. We established rat
      models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes
      associated with non-alcoholic fatty liver disease (NAFLD) and its progression.
      Histologic features of rat livers were scored according to criteria established
      by the Nonalcoholic Steatohepatitis Clinical Research Network. Microarray was
      performed to assess gene expression changes in rat livers. We find that gene
      expression of s100a9 was higher in NAFL group compared with control, and was
      increased in NASH groups and decreased in NAFL + T2DM group compared with NAFL.
      In contrast, srebf1, tbx21, and gimap4 only showed limited discriminating
      abilities in different groups. There is a significant positive correlation
      between serum levels of S100A9 and NAFLD Activity Score (NAS), the severity of
      hepatic steatosis, and lobular inflammation (r = 0.80, 0.64 and 0.86, P < 0.001).
      These findings suggest that S100A9 may be extremely useful in the diagnosis of
      NASH (AUROC: 0.947, CI: 0.845-1.049). Additionally, serum S100A9 levels displayed
      a strong correlation with ALT, AST and TBil (r = 0.81, 0.89 and 0.91, P < 0.001)
      but a weak correlation with FBG, HOMA-IR, TG, and TC (r = -0.41, -0.40, 0.47 and
      0.49, P < 0.05). CONCLUSIONS: The results we provide here suggest that S100A9 may
      be useful as a biomarker for the hepatic and metabolic progression of NAFLD and
      the non-invasive diagnosis of NASH.

PMID- 25993653
TI  - Effects of sitting and standing on upper extremity physical exposures in
      materials handling tasks.
AB  - Sitting or standing work configurations modulate musculoskeletal risk. Most
      existing investigations of these configurations have either studied them
      separately or lacked focus on the upper extremity, particularly during manual
      materials handling (MMH) tasks. To address this gap, upper extremity loading in
      20 male and 20 females were assessed in 4 MMH tasks in sitting and standing.
      Differences in electromyographic (EMG) activity, local joint moments and body
      discomfort between configurations were examined. Interactions between task and
      sit/stand configuration resulted in increases of up to 500% in joint moments, 94%
      in EMG activity and 880% in discomfort when tasks were completed while sitting (p
      < 0.01). Future MMH task designers should consider placing workers in standing
      postures when feasible to reduce upper extremity loading, but workers should not
      remain in either configuration for extended periods of time as the negative
      effects of both workspace geometries can instigate future musculoskeletal
      disorders. Practitioner Summary: Sitting and standing modify occupational
      musculoskeletal risk. We examined how performing identical tasks while sitting or
      standing altered upper extremity and low back loading. In general, sitting
      increased muscle activity and discomfort, while standing increased local joint
      moments. The benefits of standing outweighed those of sitting across the range of
      tasks. 

PMID- 25993654
TI  - Effect of Mandatory Centers of Excellence Designation on Demographic
      Characteristics of Patients Who Undergo Bariatric Surgery.
AB  - IMPORTANCE: From February 21, 2006, through September 24, 2013, the Centers for
      Medicare & Medicaid Services (CMS) required, via the National Coverage
      Determination manual, that bariatric surgery be performed only in hospitals that
      had been designated as a Center of Excellence (COE). The effect of this
      certification requirement on access to bariatric surgery has been reported only
      anecdotally. OBJECTIVE: To investigate whether the COE certification requirement
      proved to be a barrier to patients' access to bariatric surgical procedures.
      DESIGN, SETTING, AND PARTICIPANTS: Using the National Inpatient Sample, we
      retrospectively identified patients who underwent bariatric surgery from January
      1, 2006, through December 31, 2011. EXPOSURE: Bariatric surgery. MAIN OUTCOMES
      AND MEASURES: Logistic regression and chi2 tests were used to examine differences
      in patients' sociodemographic characteristics over time. RESULTS: A total of
      134,227 bariatric surgical patients were identified. The proportion of the
      population who were older than 64 years increased from 2.9% in 2006 to 7.0% in
      2011 (P < .001) and there was a decrease in the proportion of patients who were
      49 years and younger (P < .001). The percentage of female patients who underwent
      bariatric surgery decreased from 80.4% to 78.1% (P < .001) and the percentage of
      patients who were classified as black, Hispanic, or Asian or Pacific Islander
      increased from 12.3% to 15.1% (P < .001), 9.7% to 12.5% (P < .001), and 0.3% to
      0.4% (P < .001), respectively. The proportion of patients with Medicare increased
      from 8.5% to 16.3% (P < .001) and those with Medicaid from 6.6% to 11.8% (P <
      .001). The percentage of patients with private insurance declined from 72.4% to
      63.3% (P < .001). The proportion of patients in the lowest income quartile
      increased from 20.7% to 22.9% (P < .001) while those in the highest income
      quartile decreased from 25.8% to 23.9% (P < .001). CONCLUSIONS AND RELEVANCE: The
      COE certification requirement by CMS did not appear to limit access to bariatric
      surgery. Future studies should determine whether CMS's recent (2013) change in
      policy (ie, removing the mandatory COE certification for bariatric surgical
      insurance coverage) might sacrifice patient safety without addressing the real
      cause of limited access to health care.

PMID- 25993655
TI  - Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1
      Cells.
AB  - Immunotherapy has emerged as a promising strategy for the treatment of metastatic
      melanoma. Clinical studies have demonstrated the feasibility of cancer
      immunotherapy using tumor antigens recognized by CD8(+) T cells. However, the
      overall immune responses induced by these antigens are too weak and transient to
      induce tumor regression in the majority of patients who received immunization. A
      growing body of evidence suggests that CD4(+) T helper (Th) cells play an
      important role in antitumor immunity. Therefore, the identification of MHC class
      II-restricted tumor antigens capable of stimulating CD4(+) T cells may provide
      opportunities for developing effective cancer vaccines. To this end, we describe
      the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as
      a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+) Th1 cells.
      Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was
      required for T cell recognition. Reverse transcription-polymerase chain reaction
      revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal
      tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell
      proliferation and soft agar colony formation. Taken together, these data suggest
      that DRG-1 plays an important role in melanoma cell growth and transformation,
      indicating that DRG1 may represent a novel target for CD4(+) T cell-mediated
      immunotherapy in melanoma.

PMID- 25993656
TI  - High Intake of Energy and Fat in Southwest Chinese Women with PCOS: A Population
      Based Case-Control Study.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive
      endocrinological disease with heterogeneous phenotype. Obesity contributes to the
      increased prevalence and severity of PCOS. Whether the intakes of major nutrients
      are higher in Chinese PCOS patients is still unknown. OBJECTIVES: To study the
      intakes of total energy, protein, fat and carbohydrate in Southwest Chinese PCOS
      patients. METHODS: 1854 women were included in the cross-sectional study. A
      population-based case-control study was conducted. The dietary habits and
      nutrients intake status of 169 PCOS patients and 338 age-matched controls were
      investigated by the method of semi-quantitative food frequency questionnaire.
      RESULTS: The actual intake of total energy (P = 0.01) and fat (P = 0.01) were
      higher, but carbohydrate was lower (P = 0.01) in PCOS patients as compared with
      the controls. The energy percentage supplied by protein (12.33% +/- 2.27% vs.
      19.26% +/- 5.91%, P<0.001) and carbohydrate (48.72% +/- 6.41% vs. 68.31% +/-
      8.37%, P<0.001) were lower in Southwest Chinese PCOS patients than those of
      control, however, the energy percentage supplied by fat was higher (38.95% +/-
      5.71% vs. 12.42% +/- 5.13%, P<0.001) in PCOS. CONCLUSIONS: Limit the intake of
      total energy and fat shall be recommended to the Southwest Chinese PCOS patients.
      Women with PCOS in Southwest China shall consult with the nutritionist for
      improving the dietary structure.

PMID- 25993657
TI  - Analysis of Mexico's Narco-War Network (2007-2011).
AB  - Since December 2006, more than a thousand cities in Mexico have suffered the
      effects of the war between several drug cartels, amongst themselves, as well as
      with Mexican armed forces. Sources are not in agreement about the number of
      casualties of this war, with reports varying from 30 to 100 thousand dead; the
      economic and social ravages are impossible to quantify. In this work we analyze
      the official report of casualties in terms of the location and the date of
      occurrence of the homicides. We show how the violence, as reflected by the number
      of casualties, has increased over time and spread across the country. Next, based
      on the correlations between cities in the changes of the monthly number of
      casualties attributed to organized crime, we construct a narco-war network where
      nodes are the affected cities and links represent correlations between them. We
      find that close geographical distance between violent cities does not imply a
      strong correlation amongst them. We observe that the dynamics of the conflict has
      evolved in short-term periods where a small core of violent cities determines the
      main theatre of the war at each stage. This kind of analysis may also help to
      describe the emergence and propagation of gang-related violence waves. 

PMID- 25993658
TI  - Flow and Heat Transfer to Sisko Nanofluid over a Nonlinear Stretching Sheet.
AB  - The two-dimensional boundary layer flow and heat transfer to Sisko nanofluid over
      a non-linearly stretching sheet is scrutinized in the concerned study. Our
      nanofluid model incorporates the influences of the thermophoresis and Brownian
      motion. The convective boundary conditions are taken into account. Implementation
      of suitable transformations agreeing with the boundary conditions result in
      reduction of the governing equations of motion, energy and concentration into non
      linear ordinary differential equations. These coupled non-linear ordinary
      differential equations are solved analytically by using the homotopy analysis
      method (HAM) and numerically by the shooting technique. The effects of the
      thermophoresis and Brownian motion parameters on the temperature and
      concentration fields are analyzed and graphically presented. The secured results
      make it clear that the temperature distribution is an increasing function of the
      thermophoresis and Brownian motion parameters and concentration distribution
      increases with the thermophoresis parameter but decreases with the Brownian
      motion parameter. To see the validity of the present work, we made a comparison
      with the numerical results as well as previously published work with an
      outstanding compatibility. 

PMID- 25993659
TI  - Innate lymphotoxin receptor mediated signaling promotes HSV-1 associated
      neuroinflammation and viral replication.
AB  - Host anti-viral innate immunity plays important roles in the defense against HSV
      1 infection. In this study, we find an unexpected role for innate LT/LIGHT
      signaling in promoting HSV-1 replication and virus induced inflammation in
      immunocompromised mice. Using a model of footpad HSV-1 infection in Rag1(-/-)
      mice, we observed that blocking LT/LIGHT signaling with LTbetaR-Ig could
      significantly delay disease progression and extend the survival of infected mice.
      LTbetaR-Ig treatment reduced late proinflammatory cytokine release in the serum
      and nervous tissue, and inhibited chemokine expression and inflammatory cells
      infiltration in the dorsal root ganglia (DRG). Intriguingly, LTbetaR-Ig treatment
      restricted HSV-1 replication in the DRG but not the footpad. These findings
      demonstrate a critical role for LT/LIGHT signaling in modulating innate
      inflammation and promoting HSV-1 replication in the nervous system, and suggest a
      new target for treatment of virus-induced adverse immune response and control of
      severe HSV-1 infection. 

PMID- 25993660
TI  - Evidence that selenium binding protein 1 is a tumor suppressor in prostate
      cancer.
AB  - Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated
      protein shown to be at lower levels in tumors, and its lower levels are
      frequently predictive of a poor clinical outcome. Distinguishing indolent from
      aggressive prostate cancer is a major challenge in disease management.
      Associations between SBP1 levels, tumor grade, and disease recurrence following
      prostatectomy were investigated by duplex immunofluorescence imaging using a
      tissue microarray containing tissue from 202 prostate cancer patients who
      experienced biochemical (PSA) recurrence after prostatectomy and 202 matched
      control patients whose cancer did not recur. Samples were matched by age,
      ethnicity, pathological stage and Gleason grade, and images were quantified using
      the Vectra multispectral imaging system. Fluorescent labels were targeted for
      SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell
      quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1
      levels and the nuclear to cytoplasm ratio were inversely associated with tumor
      grade using linear regression analysis. Following classification of samples into
      quartiles based on the SBP1 levels among controls, tumors in the lowest quartile
      were more than twice as likely to recur compared to those in any other quartile.
      Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor
      cells to grow in soft agar, a measure of transformation, without affecting
      proliferation. Cells expressing SBP1 also demonstrated a robust induction in the
      phosphorylation of the p53 tumor suppressor at serine 15. These data indicate
      that loss of SBP1 may play an independent contributing role in prostate cancer
      progression and its levels might be useful in distinguishing indolent from
      aggressive disease. 

PMID- 25993661
TI  - WITHDRAWN: Adjusting the pH of lidocaine for reducing pain on injection.

PMID- 25993662
TI  - Interactions between tick and transmitted pathogens evolved to minimise
      competition through nested and coherent networks.
AB  - Natural foci of ticks, pathogens, and vertebrate reservoirs display complex
      relationships that are key to the circulation of pathogens and infection dynamics
      through the landscape. However, knowledge of the interaction networks involved in
      transmission of tick-borne pathogens are limited because empirical studies are
      commonly incomplete or performed at small spatial scales. Here, we applied the
      methodology of ecological networks to quantify >14,000 interactions among ticks,
      vertebrates, and pathogens in the western Palearctic. These natural networks are
      highly structured, modular, coherent, and nested to some degree. We found that
      the large number of vertebrates in the network contributes to its robustness and
      persistence. Its structure reduces interspecific competition and allows ample but
      modular circulation of transmitted pathogens among vertebrates. Accounting for
      domesticated hosts collapses the network's modular structure, linking groups of
      hosts that were previously unconnected and increasing the circulation of
      pathogens. This framework indicates that ticks and vertebrates interact along the
      shared environmental gradient, while pathogens are linked to groups of
      phylogenetically close reservoirs. 

PMID- 25993663
TI  - Surface modeling of workpiece and tool trajectory planning for spray painting
      robot.
AB  - Automated tool trajectory planning for spray-painting robots is still a
      challenging problem, especially for a large free-form surface. A grid
      approximation of a free-form surface is adopted in CAD modeling in this paper. A
      free-form surface model is approximated by a set of flat patches. We describe
      here an efficient and flexible tool trajectory optimization scheme using T-Bezier
      curves calculated in a new way from trigonometrical bases. The distance between
      the spray gun and the free-form surface along the normal vector is varied.
      Automotive body parts, which are large free-form surfaces, are used to test the
      scheme. The experimental results show that the trajectory planning algorithm
      achieves satisfactory performance. This algorithm can also be extended to other
      applications. 

PMID- 25993664
TI  - HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and
      Autoantibodies in Mexican Systemic Sclerosis (SSc) Patients.
AB  - INTRODUCTION: Human leukocyte antigen (HLA) polymorphism studies in Systemic
      Sclerosis (SSc) have yielded variable results. These studies need to consider the
      genetic admixture of the studied population. Here we used our previously reported
      definition of genetic admixture of Mexicans using HLA class I and II DNA blocks
      to map genetic susceptibility to develop SSc and its complications. METHODS: We
      included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed
      clinical evaluation, obtained SSc-associated antibodies, and determined HLA class
      I and class II alleles using sequence-based, high-resolution techniques to
      evaluate the contribution of these genes to SSc susceptibility, their correlation
      with the clinical and autoantibody profile and the prevalence of Amerindian,
      Caucasian and African alleles, blocks and haplotypes in this population. RESULTS:
      Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map
      susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map
      the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05
      and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also
      confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility
      to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using
      three Amerindian blocks. We also found a significant association for the presence
      of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian
      block (DRB1*08:02-DQB1*04:02), and we found several alleles associated to
      internal organ damage. The admixture estimations revealed a lower proportion of
      the Amerindian genetic component among SSc patients. CONCLUSION: This is the
      first report of the diversity of HLA class I and II alleles and haplotypes
      Mexican patients with SSc. Our findings suggest that HLA class I and class II
      genes contribute to the protection and susceptibility to develop SSc and its
      different clinical presentations as well as different autoantibody profiles in
      Mexicans.

PMID- 25993665
TI  - Livestock-associated MRSA in household members of pig farmers: transmission and
      dynamics of carriage, a prospective cohort study.
AB  - This prospective cohort study describes carriage of livestock-associated
      methicillin-resistant Staphylococcus aureus (LA-MRSA) in household members from
      49 farrowing pig farms in the Netherlands (2010-2011). Of 171 household members,
      4% were persistent MRSA nasal carriers, and the MRSA prevalence on any given
      sampling moment was 10% (range 7-11%). Working in the stables (of which 98% was
      MRSA-positive, prevalence ratio (PR) = 2.11 per 10 hours), working with sows
      (PR=1.97), and living with an MRSA-positive pig farmer (PR=4.63) were significant
      determinants for MRSA carriage. Significant protective factors were carriage of
      methicillin-susceptible Staphylococcus aureus (MSSA) (PR=0.50), and wearing a
      facemask when working in the stables (37% decreased prevalence). All MRSA strains
      during the study period were known livestock-associated types. The bacteriophage
      phi3 was not found in household members. Transmission from pigs and the
      environment appeared to be important determinants; human-to-human transmission
      could not sufficiently be differentiated. Wearing a facemask when working in the
      stables and carriage of MSSA are potential interventional targets. 

PMID- 25993666
TI  - Elimination of HIV-1-Infected Primary T Cell Reservoirs in an In Vitro Model of
      Latency.
AB  - Establishment of long-lived cellular reservoirs of HIV-1 represents a major
      therapeutic challenge to virus eradication. In this study, we utilized a human
      primary cell model of HIV-1 latency to evaluate the requirements for efficient
      virus reactivation from, and the selective elimination of, latently infected
      human T cells. Ectopic expression of BCL2 supported the replication and spread of
      R5-tropic HIV-1 in activated CD4(+) T cells. After IL-2 withdrawal, the HIV-1
      infected T cells survived as resting cells for several months. Unexpectedly,
      these resting T cells continue to produce detectable levels of infectious virus,
      albeit at a lower frequency than cells maintained in IL-2. In the presence of HIV
      1 inhibitors, reactivation of the resting T cells with gammac-cytokines and
      allogeneic dendritic cells completely extinguished HIV-1 infectivity. We also
      evaluated the ability of the bacterial LukED cytotoxin to target and kill CCR5
      expressing cells. After gammac-cytokine stimulation, LukED treatment eliminated
      both HIV-1-infected resting cells and the non-infected CCR5+ cells. Importantly,
      complete clearance of in vitro HIV-1 reservoirs by LukED required a lower
      threshold of cytokine signals relative to HIV-1 inhibitors. Thus, the primary T
      cell-based HIV-1 latency model could facilitate the development of novel agents
      and therapeutic strategies that could effectively eradicate HIV-1.

PMID- 25993667
TI  - Asymptomatic vertebral fracture: a wolf in sheep's clothing?

PMID- 25993668
TI  - Puberty: when is it normal?

PMID- 25993669
TI  - Autoimmune thyroid disease: what secrets we still need to unravel?

PMID- 25993670
TI  - Digital vertebral morphometry performed by DXA: a valuable opportunity for
      identifying fractures during bone mass assessment.
AB  - OBJECTIVES: To evaluate the usefulness of vertebral morphometry in identifying
      unreferred vertebral fractures and correlate potential risk factors. SUBJECTS AND
      METHODS: Female patients above 45 years, postmenopausal for at least 2 years,
      diagnosed with osteoporosis and undergoing treatment for at least three months
      were considered eligible. All of them underwent bone densitometry and vertebral
      morphometry performed by concomitant DXA. The presence of fractures was defined
      between T7 and L4; only moderate and severe fractures were considered for
      analysis. All volunteers were submitted to laboratory tests, anthropometry and
      responded a questionnaire on their lifestyle habits and medical history. RESULTS:
      Thirty two (17%) out of the 188 female patients presented with at least one
      vertebral fracture, among whom only 4 (12.5%) were previously aware of the
      fracture. The fractures were mainly located on the thoracic spine. Nine patients
      had severe fractures (28.1%), whereas 23 had moderate fractures (71.9%). On
      average, patients with fractures were 5 years older and weighed 5 kilograms less
      than those without fractures. The creatinine clearance was on average 9 mL/min
      less in patients with vertebral fracture. The assessment of vertebral fractures
      by morphometry is a fast, accurate and complementary method associated with low
      radiation exposure for identifying moderate and severe vertebral fractures.
      Predisposition to vertebral fractures does not depend solely on BMD.

PMID- 25993671
TI  - Puberty in a sample of Brazilian schoolgirls: timing and anthropometric
      characteristics.
AB  - OBJECTIVE: The objective of this study was to determine the age at which puberty
      begins, age of menarche and anthropometric data of the participants at different
      stages of puberty. SUBJECTS AND METHODS: This is a cross-sectional study in which
      we evaluated 665 girls, a sample representing the female schoolchildren
      population in Uberaba. RESULTS: We found that thelarche, pubarche, underarm hair
      and menarche were attained at the age of 9.8 +/- 1.4, 10.2 +/- 1.4, 10.5 +/- 1.5
      and 11.7 +/- 1.3 years, respectively. The mean interval between thelarche and
      menarche (ITM) was 1.7 +/- 1.3 years. The prevalence of overweight and obesity
      was 31.3% and 95% of the participants began at thelarche between the age of 7 and
      12 years. CONCLUSION: These values indicate a secular tendency to the decrease of
      the age of menarche and an earlier start of puberty. It is very important to
      understand these parameters to establish public policies aimed at plans to
      prevent these early events, especially regarding control of the prevalence of
      obesity.

PMID- 25993672
TI  - Thyroid disorders are common in first-degree relatives of individuals with type 1
      diabetes mellitus.
AB  - OBJECTIVE: Thyroid diseases are common in individuals with type 1 diabetes
      mellitus (T1DM) and should be investigated annually in these individuals. The aim
      of this study was to evaluate the frequency of thyroid diseases in first degree
      relatives (FDR) of patients with T1DM. SUBJECTS AND METHODS: Eighty individuals
      (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for
      thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase
      (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase
      65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were
      measured in FDR. RESULTS: We found a similar prevalence of thyroid dysfunction in
      patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no
      differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal
      TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in
      positive cases) between patients with T1DM and their FDR (p = 0.94). CONCLUSIONS:
      Thyroid abnormalities seem to be common not only in patients with T1DM but also
      in their FDR, which suggests that screening strategies for thyroid diseases might
      also be useful to these individuals.

PMID- 25993673
TI  - Association between antiretrovirals and thyroid diseases: a cross-sectional
      study.
AB  - OBJECTIVE: This study aims to estimate the prevalence of thyroid diseases and
      anti-TPO status. We searched for an association among presence of immune
      reconstitution and use of stavudine, didanosine and protease inhibitors with
      thyroid diseases. MATERIALS AND METHODS: A cross-sectional study was performed to
      analyze the records of 117 HIV-infected patients who had their CD4+ cell count,
      viral load, anti-TPO, TSH and free T4 levels collected on the same day. Immune
      reconstitution was considered in those whose T CD4+ count was below 200
      cells/mm3, but these values increased above 200 cells/mm3 after the use of
      antiretrovirals. The odds ratio obtained by a 2x2 contingency table and a chi
      square test were used to measure the association between categorical variables.
      RESULTS: The prevalence of thyroid disease was 34.18%; of these, 4.34% were
      positive for anti-TPO. There was an association of risk between stavudine use and
      subclinical hypothyroidism (OR = 4.19, 95% CI: 1.29 to 13.59, X2 = 6.37, p =
      0.01). Immune reconstitution achieved protection associated with thyroid disease
      that was near statistical significance OR = 0.45, 95% CI: 0.19 to 1.04, X2 =
      3.55, p = 0.059. CONCLUSION: The prevalence of thyroid disease in the sample
      studied was higher than what had been found in the literature, with a low
      positive anti-TPO frequency. The historical use of stavudine has an association
      of risk for the presence of subclinical hypothyroidism, and immune reconstitution
      has trends towards protection for the presence of thyroid diseases.

PMID- 25993674
TI  - Influence of altered maternal lipid profile on the lipid profile of the newborn.
AB  - OBJECTIVE: To evaluate whether there is an association between altered maternal
      lipid profile and the lipid profile of the newborn in a maternity hospital.
      SUBJECTS AND METHOD: Cross-sectional study with 435 parturients and their
      respective newborns. Blood samples from the newborns were collected during
      delivery by venipuncture of the umbilical cord close to the placenta. Blood
      samples from the parturients were collected in the pre-delivery room or right
      after delivery. The concentrations of total cholesterol, triglycerides and HDL-c
      were determined by an enzymatic colorimetric method and LDL-c was calculated by
      the Friedewald formula. RESULTS: There was no significant difference in mean
      concentrations of total cholesterol, LDL-c, HDL-c and triglycerides in neonates
      according to altered or non-altered maternal total cholesterol, LDL-c, HDL-c and
      triglycerides. CONCLUSIONS: Change in maternal lipid profile is not significantly
      associated with the mean concentrations of total cholesterol, LDL-c, HDL-c and
      triglycerides in newborns.

PMID- 25993675
TI  - Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings,
      Helicobacter pylori infection, and associations with metabolic control, mood
      disorders and nutritional factors.
AB  - OBJECTIVES: To evaluate, in a group of patients with long-standing type 1
      diabetes (DM1), an association of dyspepsia symptoms with: changes in the
      gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and
      psychological and nutritional factors. SUBJECTS AND METHODS: A total of 32
      patient with DM1 were studied (age: 38 +/- 9 years; females: 25; diabetes
      duration: 22 +/- 5 years). All patients answered a standardized questionnaire for
      the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal
      endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori
      infection. The presence of anxiety and depression was evaluated by the HAD scale.
      Nutritional parameters were BMI, arm and waist circumference, skinfold
      measurement, and body fat percentage. RESULTS: Upper endoscopy detected lesions
      in the gastric mucosa in 34.4% of the patients, with similar frequency in those
      with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia
      complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher
      values for HbA1c (9.6 +/- 1.7 vs. 8.2 +/- 1.3%; p = 0.01) and lower values for
      BMI (24.3 +/- 4.1 vs. 27.2 +/- 2.6 kg/m2; p = 0.02), body fat percentage (26.6 +/
      6.2 vs. 30.8 +/- 7.7%; p = 0.04), and waist circumference (78.7 +/- 8 vs. 85.8
      +/- 8.1 cm; p = 0.02). No association was found between the symptoms and the
      presence of Helicobacter pylori. CONCLUSIONS: Dyspepsia symptoms in patients with
      long-standing DM1 were associated with glycemic control and depression, and they
      seem to negatively influence the nutritional status of these patients.

PMID- 25993676
TI  - Risk of hypoglycemia during hemodialysis in diabetic patients is related to lower
      pre-dialysis glycemia.
AB  - OBJECTIVE: To compare the occurrence of hypoglycemia during hemodialysis in
      chronic kidney disease diabetic patients who present different levels of pre
      dialysis glycemia both when using dialysis solutions with and without glucose.
      SUBJECTS AND METHODS: Twenty type 2 diabetic patients in maintenance hemodialysis
      were submitted to three dialysis sessions (at a 7-day interval each) with
      dialysis solutions without glucose, with glucose at 55 mg/dL, and at 90 mg/dL
      subsequently. Blood glucose levels were measured immediately pre-dialysis and at
      4 moments during the session, and values under 70 mg/dL were considered as
      hypoglycemia. RESULTS: Average pre-dialysis glycemia was lower in those who
      presented intra-dialytic hypoglycemia than in those who did not, both in glucose
      free (140.4 +/- 50.7 vs. 277.7 +/- 91.0 mg/dL; p = 0.005; 95%CI: 46.4 to 228.1)
      and in glucose 55 mg/dL (89.5 +/- 10.6 vs. 229.7 +/- 105.0 mg/dL; p < 0.05;
      95%CI: 9.8 to 270.5). In patients with pre-dialysis glycemia under 140 mg/dL,
      average intradialytic glycemia was significantly lower than pre-dialysis glycemia
      only when using glucose-free dialysate (p < 0.0001; 95%CI: 29.9 to 56.0 - t
      test). Hypoglycemia during dialysis was observed only when using glucose-free or
      glucose-poor dialysis solutions. CONCLUSIONS: The use of glucose-free or glucose
      poor dialysis solution presents a high risk of intradialytic hypoglycemia in
      diabetic renal patients, especially in those with presumed better glycemic
      control.

PMID- 25993677
TI  - The thyroid hormone receptor beta-selective agonist GC-1 does not affect
      tolerance to exercise in hypothyroid rats.
AB  - OBJECTIVE: Investigate the effect of GC-1 on tolerance to exercise in rats with
      experimental hypothyroidism. MATERIALS AND METHODS: Hypothyroidism was induced
      with methimazole sodium and perchlorate treatment. Six groups with eight animals
      were studied: control group (C), hypothyroid group without treatment (HYPO);
      hypothyroidism treated with physiological doses of tetraiodothyronine (T4) or 10
      times higher (10*T4); hypothyroidism treated with equal molar doses of GC-1 (GC
      1) or 10 times higher (10*GC-1). After eight weeks, each animal underwent an
      exercise tolerance test by measuring the time (seconds), in which the rats were
      swimming with a load attached to their tails without being submerging for more
      than 10 sec. After the test, the animals were killed, and blood samples were
      collected for biochemical analysis, and the heart and soleus muscle were removed
      for weighing and morphometric analysis of the cardiomyocyte. RESULTS:
      Hypothyroidism significantly reduced tolerance to exercise and, treatment with GC
      1 1* or T4 in physiological doses recover tolerance test to normal parameters.
      However, high doses of T4 also decreased tolerance to physical exercise.
      Conversely, ten times higher doses of GC-1 did not impair tolerance to exercise.
      Interestingly, hypothyroidism, treated or not with T4 in a physiological range,
      GC-1 or even high doses of GC-1 (10X) did not change cardiomyocyte diameters and
      relative weight of the soleus muscle. In contrast, higher doses of T4
      significantly increased cardiomyocyte diameter and induced atrophy of the soleus
      muscle. CONCLUSION: Unlike T4, GC-1 in high doses did not modify tolerance to
      physical exercise in the rats with hypothyroidism.

PMID- 25993678
TI  - Exercise alters myostatin protein expression in sedentary and exercised
      streptozotocin-diabetic rats.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of exercise on the
      pattern of muscle myostatin (MSTN) protein expression in two important metabolic
      disorders, i.e., obesity and diabetes mellitus. MATERIALS AND METHODS: MSTN, is a
      negative regulator of skeletal muscle mass. We evaluated the effect of exercise
      on MSTN protein expression in diabetes mellitus and high fat diet-induced
      obesity. MSTN protein expression in gastrocnemius muscle was analyzed by Western
      Blot. P < 0.05 was assumed. Exercise induced a significant decrease in glycemia
      in both diabetic and obese animals. RESULTS: The expression of precursor and
      processed protein forms of MSTN and the weight of gastrocnemius muscle did not
      vary in sedentary or exercised obese animals. Diabetes reduced gastrocnemius
      muscle weight in sedentary animals. However, gastrocnemius muscle weight
      increased in diabetic exercised animals. Both the precursor and processed forms
      of muscle MSTN protein were significantly higher in sedentary diabetic rats than
      in control rats. The precursor form was significantly lower in diabetic exercised
      animals than in diabetic sedentary animals. However, the processed form did not
      change. CONCLUSION: These results demonstrate that exercise can modulate the
      muscle expression of MSTN protein in diabetic rats and suggest that MSTN may be
      involved in energy homeostasis.

PMID- 25993679
TI  - Translational research into gut microbiota: new horizons on obesity treatment:
      updated 2014.
AB  - Obesity is currently a pandemic of worldwide proportions affecting millions of
      people. Recent studies have proposed the hypothesis that mechanisms not directly
      related to the human genome could be involved in the genesis of obesity, due to
      the fact that, when a population undergoes the same nutritional stress, not all
      individuals present weight gain related to the diet or become hyperglycemic. The
      human intestine is colonized by millions of bacteria which form the intestinal
      flora, known as gut flora. Studies show that lean and overweight human may
      present a difference in the composition of their intestinal flora; these studies
      suggest that the intestinal flora could be involved in the development of
      obesity. Several mechanisms explain the correlation between intestinal flora and
      obesity. The intestinal flora would increase the energetic extraction of non
      digestible polysaccharides. In addition, the lipopolysaccharide from intestinal
      flora bacteria could trigger a chronic sub-clinical inflammatory process, leading
      to obesity and diabetes. Another mechanism through which the intestinal flora
      could lead to obesity would be through the regulation of genes of the host
      involved in energy storage and expenditure. In the past five years data coming
      from different sources established causal effects between intestinal microbiota
      and obesity/insulin resistance, and it is clear that this area will open new
      avenues of therapeutic to obesity, insulin resistance and DM2. 

PMID- 25993680
TI  - Human pancreatic islet transplantation: an update and description of the
      establishment of a pancreatic islet isolation laboratory.
AB  - Type 1 diabetes mellitus (T1DM) is associated with chronic complications that
      lead to high morbidity and mortality rates in young adults of productive age.
      Intensive insulin therapy has been able to reduce the likelihood of the
      development of chronic diabetes complications. However, this treatment is still
      associated with an increased incidence of hypoglycemia. In patients with "brittle
      T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia
      unawareness), islet transplantation may be a therapeutic option to restore both
      insulin secretion and hypoglycemic perception. The Edmonton group demonstrated
      that most patients who received islet infusions from more than one donor and were
      treated with steroid-free immunosuppressive drugs displayed a considerable
      decline in the initial insulin independence rates at eight years following the
      transplantation, but showed permanent C-peptide secretion, which facilitated
      glycemic control and protected patients against hypoglycemic episodes. Recently,
      data published by the Collaborative Islet Transplant Registry (CITR) has revealed
      that approximately 50% of the patients who undergo islet transplantation are
      insulin independent after a 3-year follow-up. Therefore, islet transplantation is
      able to successfully decrease plasma glucose and HbA1c levels, the occurrence of
      severe hypoglycemia, and improve patient quality of life. The goal of this paper
      was to review the human islet isolation and transplantation processes, and to
      describe the establishment of a human islet isolation laboratory at the Endocrine
      Division of the Hospital de Clinicas de Porto Alegre - Rio Grande do Sul, Brazil.

PMID- 25993681
TI  - Reassessing lipid metabolism and its potentialities in the prediction of
      cardiovascular risk.
AB  - There are numerous particles, enzymes, and mechanisms in the lipid metabolism
      that are involved in the genesis of cardiovascular disease (CVD). Given its
      prevalence in populations and its impact on mortality, it is relevant to review
      the lipid metabolism as it may potentially provide subsidies to better
      prediction. This article reviews the importance of traditional cardiovascular
      risk factors and comments on the potential of novel lipid biomarkers involved in
      the physiopathology of CVD. The Framingham cohorts proved the role of traditional
      risk factors (physical inactivity, smoking, blood pressure, total cholesterol,
      LDL-C, HDL-C, plasma glucose) in the prediction of cardiovascular events.
      However, a significant number of individuals that suffer from a cardiovascular
      event has few or none of these factors. Such finding indicates the need for new
      biomarkers able to identify plaques that are more susceptible to rupture. Some of
      bloodstream biomarkers related to lipid metabolism are modified LDL particles,
      apolipoprotein AI (apo AI), apolipoprotein B, lipoprotein (a) [Lp (a)],
      cholesteryl ester transfer protein (CETP), subtypes of LDL and HDL particles, and
      lipoprotein-associated phospholipase A2 (Lp-PLA2). These factors participate in
      the atherosclerotic process, and are abnormal in individuals at high risk, or in
      those who suffered from a cardiovascular event. Lp (a) determination is already
      employed in clinical practice and should be included as a reference parameter for
      CVD monitoring. Furthermore, there are expectations for wider use of apo B, non
      HDL cholesterol and total cholesterol / HDL-C determination to improve
      cardiovascular risk assessment. 

PMID- 25993682
TI  - X-linked adrenal hypoplasia congenita: clinical and follow-up findings of two
      kindreds, one with a novel NR0B1 mutation.
AB  - X-linked adrenal hypoplasia congenita typically manifests as primary adrenal
      insufficiency in the newborn age and hypogonadotropic hypogonadism in males,
      being caused by mutations in NR0B1 gene. We present the clinical and follow-up
      findings of two kindreds with NR0B1 mutations. The proband of kindred A had a
      diagnosis of primary adrenal insufficiency when he was a newborn. Family history
      was relevant for a maternal uncle death at the newborn age. Beyond 2 year-old
      steroid measurements rendered undetectable and delayed bone age was noticed.
      Molecular analysis of NR0B1 gene revealed a previously unreported mutation
      (c.1084A>T), leading to a premature stop codon, p.Lys362*, in exon 1. His mother
      and sister were asymptomatic carriers. At 14 year-old he had 3 mL of testicular
      volume and biochemical surveys (LH < 0.1 UI/L, total testosterone < 10 ng/dL)
      concordant with hypogonadotrophic hypogonadism. Kindred B had two males diagnosed
      with adrenal insufficiency at the newborn age. By 3 year-old both siblings had
      undetectable androgen levels and delayed bone age. NR0B1 molecular analysis
      identified a nonsense mutation in both cases, c.243C>G; p.Tyr81*, in exon 1.
      Their mother and sister were asymptomatic carriers. At 14 year-old (Tanner stage
      1) hypothalamic-pituitary-gonadal axis evaluation in both males (LH < 0.1UI/L,
      total testosterone < 10 ng/dL) confirmed hypogonadotropic hypogonadism. In
      conclusion, biochemical profiles, bone age and an X-linked inheritance led to
      suspicion of NR0B1 mutations. Two nonsense mutations were detected in both
      kindreds, one previously unreported (c.1084A>T; p.Lys362*). Mutation
      identification allowed the timely institution of testosterone in patients at
      puberty and an appropriate genetic counselling for relatives. 

PMID- 25993683
TI  - Spinal cord compression after radiolabeled metaiodobenzylguanidine analogue
      therapy in advanced malignant insulinoma.
AB  - Malignant insulinomas are frequently diagnosed at a late stage. Medical
      management is necessary to slow progression of the disease and control of
      hypoglycemic symptoms when cure by surgical treatment is not possible. Multimodal
      treatment, in these cases, has been used with variable clinical response. We
      describe a 68-yr-old woman who presented response failure to usual treatment and
      was alternatively treated with radiolabeled metaiodobenzylguanidine ([131I]-MIBG)
      analogue therapy with development of neurologic complications. We also present a
      review of the current role of [131I]-MIBG treatment in insulinomas. 

PMID- 25993684
TI  - Thyroid nodule: first manifestation of chronic lymphocytic leukaemia.
AB  - The presence of chronic lymphocytic leukaemia (CLL) cells in the thyroid gland is
      most likely due to a secondary involvement by a systemic disease. The reported
      incidence of CLL involving the thyroid is extremely low, representing about 3-4%
      of all thyroid lymphoproliferative neoplasm. We report a rare case of CLL
      presenting initially in the thyroid gland. Systemic disease was detected as a
      result of thyroid investigation. An 85 years old woman, with multinodular goiter
      without adenophaties, was referred to our department, carrying a fine needle
      aspiration biopsy (FNAB) report of a private institution referring "lymphoid
      monomorphic proliferation" and suggesting a "Core-needle biopsy" for further
      investigation. She was euthyroid (TSH-0.5 uU/mL (0.4-4.0), thyroid antibodies
      negative, including TRab). The patient denied systemic symptoms and at physical
      examination there were no adenophaties or organomegalies. FNAB analysis was
      repeated. Although the patient denied constitutional symptoms and there were no
      relevant findings in physical examination, technetium 99m thyroid gamagraphy (GG)
      and blood count were additionally asked. FNAB analysis concluded lymphocytic
      tiroiditis, but thyroid GG revelled global hypocaptation and blood count showed
      173.4 x 109 leukocyte/L with 94% lymphocyte. An ecoguided FNAB with flow
      cytometry identified thyroid infiltration by monotonous population of blasts with
      phenotype consistent with CLL/malignancy of mature B-cells. CLL/malignancy of
      mature B-cells was also detected in peripheral blood analysis, suggesting
      systemic disease with secondary thyroid involvement. The patient started
      chemotherapy with rituximab and chlorambucil with good response. Pos-treatment GG
      revelled "Increased levels of uptake in the middle third of the right lower lobe,
      with low uptake of the remaining parenchyma". In conclusion, good communication
      with the pathologist can improve diagnostic accuracy and dictate appropriate
      therapy. The use of techniques such as flow cytometry, immunoglobulin gene
      rearrangements, and immunohistochemistry has improved diagnostic accuracy and
      obviated more invasive procedures, such as core needle or open surgery biopsy.
      Apart from chemotherapy, immunochemotherapy with anti-CD20 and anti-CD52
      monoclonal antibodies can be used in the treatment of CLL. 

PMID- 25993685
TI  - Current reliability of the Immulite(r) assay for measurement of serum IGF-1 in
      the Brazilian adult population.

PMID- 25993686
TI  - Characterization of Arabidopsis Transcriptional Responses to Different Aphid
      Species Reveals Genes that Contribute to Host Susceptibility and Non-host
      Resistance.
AB  - Aphids are economically important pests that display exceptional variation in
      host range. The determinants of diverse aphid host ranges are not well
      understood, but it is likely that molecular interactions are involved. With
      significant progress being made towards understanding host responses upon aphid
      attack, the mechanisms underlying non-host resistance remain to be elucidated.
      Here, we investigated and compared Arabidopsis thaliana host and non-host
      responses to aphids at the transcriptional level using three different aphid
      species, Myzus persicae, Myzus cerasi and Rhopalosiphum pisum. Gene expression
      analyses revealed a high level of overlap in the overall gene expression changes
      during the host and non-host interactions with regards to the sets of genes
      differentially expressed and the direction of expression changes. Despite this
      overlap in transcriptional responses across interactions, there was a stronger
      repression of genes involved in metabolism and oxidative responses specifically
      during the host interaction with M. persicae. In addition, we identified a set of
      genes with opposite gene expression patterns during the host versus non-host
      interactions. Aphid performance assays on Arabidopsis mutants that were selected
      based on our transcriptome analyses identified novel genes contributing to host
      susceptibility, host defences during interactions with M. persicae as well to non
      host resistance against R. padi. Understanding how plants respond to aphid
      species that differ in their ability to infest plant species, and identifying the
      genes and signaling pathways involved, is essential for the development of novel
      and durable aphid control in crop plants. 

PMID- 25993687
TI  - Anti-inflammatory Effects of Ganoderma lucidum Triterpenoid in Human Crohn's
      Disease Associated with Downregulation of NF-kappaB Signaling.
AB  - BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the
      gastrointestinal tract. Current medications have potentially serious side
      effects. Hence, there is increasing interest in alternative therapies. We
      previously demonstrated the anti-inflammatory effects of Food Allergy Herbal
      Formula-2 in vitro on peripheral blood mononuclear cells (PBMCs) and mucosa from
      CD subjects. Here, we investigated the anti-inflammatory effects of a bioactive
      compound isolated from Ganoderma lucidum (G. lucidum), a key herbal constituent
      of Food Allergy Herbal Formula-2, in CD in vitro. METHODS: Triterpene ganoderic
      acid C1 (GAC1) was isolated from G. lucidum. Stimulated RAW 264.7 macrophages
      were treated with GAC1. Human PBMCs and colonic biopsies were obtained from
      children with CD and cultured with or without GAC1. TNF-alpha and other
      proinflammatory cytokine levels were measured in the culture supernatant. NF
      kappaB signaling was investigated in PBMCs and colonic mucosa treated with GAC1
      by In-Cell Western and Western blot analysis. RESULTS: GAC1 decreased TNF-alpha
      production by macrophages and PBMCs from CD subjects. GAC1 significantly
      decreased TNF-alpha, IFN-gamma, and IL-17A production by inflamed colonic
      biopsies from CD subjects. These effects were due to downregulation of the NF
      kappaB signaling pathway. CONCLUSIONS: GAC1 inhibited production of TNF-alpha and
      other proinflammatory cytokines by PBMCs and inflamed CD colonic mucosa due to
      blockage of NF-kappaB activation. GAC1 is a key beneficial constituent in G.
      lucidum and the Food Allergy Herbal Formula-2 in suppressing the inflammatory
      cytokines found in CD and warrants clinical investigation for the treatment of
      CD.

PMID- 25993688
TI  - Monocytosis and a Low Lymphocyte to Monocyte Ratio Are Effective Biomarkers of
      Ulcerative Colitis Disease Activity.
AB  - BACKGROUND: Current biomarkers in ulcerative colitis (UC) are limited by their
      performance, cost, and limited availability in daily practice. This study
      examined alterations in the leukocyte profiles as biomarkers of UC activity,
      including the effects of age, gender, and medications. METHODS: Case-control
      study that included 110 UC subjects, 75 subjects with Clostridium difficile
      infection, and 75 non-inflammatory bowel disease (IBD) subjects, randomly
      selected from a single-institution IBD database. Mean values of neutrophils (N),
      lymphocytes (L), monocytes (M) and their ratios were compared between groups.
      Receiver operator curve analyses assessed the performance of each biomarker in
      discriminating disease states. Subgroup analyses examined leukocytes profiles
      with endoscopic activity. RESULTS: Elevated monocyte counts and decreased L/M
      values significantly differed between subjects with active UC and UC in remission
      and performed better than the other leukocyte profiles. A monocyte count of 483
      and L/M ratio of 3.1 were 60% sensitive and had a specificity of 61% and 53%,
      respectively for active UC. Monocyte count >860 and L/M value <1.6 had a 75%
      positive predictive value for UC activity. Those markers also correlated with
      endoscopically active disease. L/M and N/L values performed best at
      differentiating active UC from non-IBD controls, whereas N/L and N values
      performed best at differentiating from C. difficile controls. CONCLUSIONS:
      Monocytosis and a low L/M ratio might be effective, readily available, and low
      cost biomarkers to identify disease activity in UC patients. N/L values were more
      effective in distinguishing active UC patients from patients without IBD and
      those with C. difficile infection.

PMID- 25993689
TI  - Use of Intravenous Immunoglobulin for Patients with Inflammatory Bowel Disease
      with Contraindications or Who Are Unresponsive to Conventional Treatments.
AB  - BACKGROUND: Managing patients with IBD who are refractory or have
      contraindications to standard therapies is challenging. Many will lose response,
      become intolerant to treatment, or develop infections with contraindication for
      immunosuppression. Therefore, alternative therapies, such as the use of
      intravenous immunoglobulin (IVIg), could be used to manage patients in these
      difficult cases. METHODS: Data were extracted retrospectively from the electronic
      medical records at Vanderbilt University on patients with IBD who received IVIg
      (February 2011-June 2013). Patients were treated with IVIg 0.4 g.kg.d for 3
      consecutive days and then 0.4 g/kg once monthly. The dose was increased to 0.4
      g/kg biweekly for loss of response or partial response. Clinical response was
      defined as decreasing the Harvey-Bradshaw Index >=3 points or improvement in C
      reactive protein >25%. Clinical remission was defined as Harvey-Bradshaw Index
      score <5, no hospitalizations or surgeries after IVIg, or symptom resolution.
      Statistical analysis was performed using Wilcoxon signed-rank test. RESULTS:
      Twenty-four patients with IBD received IVIg. Seventeen patients received IVIg for
      failure of standard treatment. Six patients received IVIg during active
      infection. Two patients had histoplasmosis, 1 patient had tuberculosis, and 2
      patients had pulmonary fungal infections. One patient with ulcerative colitis was
      given IVIg for recurrent Clostridium difficile. Nine patients required dose
      escalation after median 153 days (30-360). Ninteen patients (79%) had a response
      or remission. Sixteen (67%) had a response and 3 (12.5%) obtained remission with
      IVIg. C-reactive protein decreased significantly after treatment (19 mg/dL [0.1
      77] to 7.5 [0.2-20]), P < 0.05. Harvey-Bradshaw Index scores improved (8 [0-19]
      to 6 [0-17]), P = not significant. Of note, 62.5% had endoscopic improvement
      after treatment. CONCLUSIONS: IVIg is safe and effective in the short-term
      management of patients with IBD when standard therapies are contraindicated.

PMID- 25993690
TI  - Endomicroscopy Will Track Injected Mesenchymal Stem Cells in Rat Colitis Models.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have demonstrated significant
      potentials for the treatment of inflammatory bowel disease. Clinical feasible
      methods to individually document the MSC recruitment to intestinal mucosa is
      lacking. Here, we proposed that endomicroscopy could noninvasively track MSCs in
      vivo at cellular resolution. METHOD: Isolated Sprague Dawley rat MSC was
      characterized, fluorescently labeled, and imaged ex vivo using an endomicroscope.
      Then enhanced green fluorescent protein (eGFP)-labeled MSC was tracked in vivo,
      and acquired images were compared with immunofluorescence, immunohistology, and
      fluorescent in situ hybridization results. RESULTS: Endomicroscopy visualized
      clearly the eGFP-labeled or carboxyfluorescein succinimidyl ester-stained MSC ex
      vivo. Endomicroscopy using the FIVE1 system could track eGFP-labeled MSC with
      distinct in vivo features. Immunofluorescence, immunohistochemistry, and
      fluorescent in situ hybridization confirmed the presence of eGFP-positive cells.
      In vivo endomicroscopy could quantify the transplanted MSCs that homed to colonic
      mucosa of the recipient rat in multiple models, including the rat-to-rat
      allograft, human-to-rat xenograft, hypoxia-induced MSC, and busulfan
      immunosuppressed recipient rat models. After hypoxia induction, there was a trend
      of enhanced rat MSC homing to the inflamed mucosa as visualized by endomicroscopy
      (114.1 in hypoxia group versus 34.3 in other 3 groups combined, t = 2.14, P =
      0.0644). CONCLUSIONS: Endomicroscopy is a novel and promising tool to track
      transplanted MSCs to the colonic mucosa. This clinical available noninvasive
      cellular tracking method may provide new insight to individualize each
      recipient's regimen in the future.

PMID- 25993691
TI  - Alternatively Spliced EDA Domain of Fibronectin Is a Target for Pharmacodelivery
      Applications in Inflammatory Bowel Disease.
AB  - The antibody-based pharmacodelivery of cytokines to sites of disease has been
      extensively studied for various indications but not for the treatment of
      inflammatory bowel diseases. Here, we report that the alternatively spliced EDA
      domain of fibronectin, a marker of angiogenesis and of tissue remodeling, is
      expressed in the dextran sodium sulfate mouse model of colitis and in patients
      with inflammatory bowel conditions, while being virtually undetectable in most
      normal adult tissues. Radiolabeled preparations of the F8 antibody, specific to
      the EDA domain of fibronectin, were shown to selectively localize to sites of
      inflammation in mice with colitis, as revealed by autoradiographic analysis.
      Fusion proteins of the F8 antibody with various murine payloads (interleukin-4,
      the p40 subunit of interleukin-12, interleukin-13) were administered to mice with
      colitis. IL12p40-F8 mediated an anti-inflammatory activity, which was comparable
      with the one of cyclosporine, whereas F8-IL4 did not inhibit colitis and F8-IL13
      worsened the inflammatory conditions. 

PMID- 25993692
TI  - Clinical and Electrodiagnostic Findings in Patients with Peripheral Neuropathy
      and Inflammatory Bowel Disease.
AB  - BACKGROUND: Several neurological diseases, especially different types of
      peripheral neuropathy (PN) are common in inflammatory bowel disease (IBD).
      METHODS: We prospectively evaluated the presence of PN in 121 patients with IBD
      (51 with Crohn's disease [CD] and 70 with ulcerative colitis [UC]) and 50
      controls (gastritis and dyspepsia) over 3.5 years. RESULTS: A total of 15
      patients (12.4%) with small-fiber neuropathy and IBD (7 CD and 8 UC) and 24
      patients (19.8%) with large-fiber PN (12 CD and 12 UC) were diagnosed. Small
      fiber neuropathy affected 6% and large-fiber PN affected 4% of the control
      patients. Patients with CD with PN were older, had more metabolic complications
      and more severe motor involvement than patients with UC with PN. Carpal tunnel
      syndrome was more common in patients with UC. Sural and median sensory nerves
      were the most commonly and severely affected sensory responses. Tibial, peroneal,
      median, and ulnar compound muscle action potential amplitudes were also
      significantly decreased in patients with CD and UC. In general, sensory and motor
      amplitudes were a more sensitive marker for PN in patients with IBD than
      conduction velocities. CONCLUSIONS: In summary, PN is common in patients with
      IBD. It may be primarily related to IBD, phenotypically modified by metabolic
      complications. Its phenotype is diverse (most commonly small to predominantly
      axonal sensory large-fiber), but usually more severe in CD. It also includes
      ataxic and demyelinating forms. Results from our 10-year follow-up will elucidate
      the PN clinical course and the real impact of the comorbidities and new
      therapies.

PMID- 25993693
TI  - Risk of Lymphoma, Colorectal and Skin Cancer in Patients with IBD Treated with
      Immunomodulators and Biologics: A Quebec Claims Database Study.
AB  - BACKGROUND: Immunomodulatory medications in patients with inflammatory bowel
      disease (IBD) have been associated with an increased risk of developing certain
      malignancies. The aim of this study was to evaluate the risk of melanoma,
      nonmelanoma skin cancer, colorectal cancer and lymphoma associated with
      immunomodulators and biologics in patients with IBD. METHODS: A nested case
      control study was carried out using the provincial health insurance database of
      Quebec, Canada (RAMQ/MedECHO). RESULTS: A total of 41,176 patients with IBD were
      identified of whom 19,582 patients were eligible for inclusion in the study.
      Treatment with thiopurine for more than 5 years was associated with a
      significantly increased risk of nonmelanoma skin cancer (odds ratio: 1.78; 95%
      confidence interval, 1.25-2.54). Immunomodulator treatment was not associated
      with an increased risk of non-Hodgkin's lymphoma (odds ratio: 0.87; 95%
      confidence interval, 0.53-1.41). Neither immunomodulators nor anti-TNF-alpha
      agents were associated with an increased risk of melanoma or colorectal cancer.
      CONCLUSIONS: In a large provincial IBD cohort, treatment with immunomodulators
      for more than 5 years was associated with an increased risk of non-melanoma skin
      cancer, whereas the risk of lymphoma, melanoma, and colorectal cancer was not
      increased. No association was found between the risk of the evaluated
      malignancies and anti-TNF-alpha medications.

PMID- 25993695
TI  - Reply to Thalidomide Treatment of Pediatric Ulcerative Colitis: A New Use for an
      Old Drug.

PMID- 25993694
TI  - Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of
      Intestinal Biopsies.
AB  - BACKGROUND: The etiology of the inflammatory bowel diseases, including ulcerative
      colitis (UC), remains incompletely explained. We hypothesized that an analysis of
      the UC colon proteome could reveal novel insights into the disease etiology.
      METHODS: Mucosal colon biopsies were taken by endoscopy from noninflamed tissue
      of 10 patients with UC and 10 controls. The biopsies were either snap-frozen for
      protein analysis or prepared for histology. The protein content of the biopsies
      was characterized by high-throughput gel-free quantitative proteomics, and biopsy
      histology was analyzed by light microscopy and confocal microscopy. RESULTS: We
      identified and quantified 5711 different proteins with proteomics. The abundance
      of the proteins calprotectin and lactotransferrin in the tissue correlated with
      the degree of tissue inflammation as determined by histology. However, fecal
      calprotectin did not correlate. Forty-six proteins were measured with a
      statistically significant differences in abundances between the UC colon tissue
      and controls. Eleven of the proteins with increased abundances in the UC biopsies
      were associated with neutrophils and neutrophil extracellular traps. The findings
      were validated by microscopy, where an increased abundance of neutrophils and the
      presence of neutrophil extracellular traps by extracellular DNA present in the UC
      colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil
      extracellular traps, and several proteins that play a part in innate immunity are
      all increased in abundance in the morphologically normal colon mucosa from
      patients with UC. The increased abundance of these antimicrobial compounds points
      to the stimulation of the innate immune system in the etiology of UC.

PMID- 25993698
TI  - On the Opportunities and Challenges in Microwave Medical Sensing and Imaging.
AB  - Widely used medical imaging systems in clinics currently rely on X-rays, magnetic
      resonance imaging, ultrasound, computed tomography, and positron emission
      tomography. The aforementioned technologies provide clinical data with a variety
      of resolution, implementation cost, and use complexity, where some of them rely
      on ionizing radiation. Microwave sensing and imaging (MSI) is an alternative
      method based on nonionizing electromagnetic (EM) signals operating over the
      frequency range covering hundreds of megahertz to tens of gigahertz. The
      advantages of using EM signals are low health risk, low cost implementation, low
      operational cost, ease of use, and user friendliness. Advancements made in
      microelectronics, material science, and embedded systems make it possible for
      miniaturization and integration into portable, handheld, mobile devices with
      networking capability. MSI has been used for tumor detection, blood clot/stroke
      detection, heart imaging, bone imaging, cancer detection, and localization of in
      body RF sources. The fundamental notion of MSI is that it exploits the tissue
      dependent dielectric contrast to reconstruct signals and images using radar-based
      or tomographic imaging techniques. This paper presents a comprehensive overview
      of the active MSI for various medical applications, for which the motivation,
      challenges, possible solutions, and future directions are discussed. 

PMID- 25993697
TI  - The epidemiology of soil-transmitted helminths in Bihar State, India.
AB  - BACKGROUND: Soil-transmitted helminths (STHs) infect over a billion individuals
      worldwide. In India, 241 million children are estimated to need deworming to
      avert the negative consequences STH infections can have on child health and
      development. In February-April 2011, 17 million children in Bihar State were
      dewormed during a government-led school-based deworming campaign. Prior to
      programme implementation, a study was conducted to assess STH prevalence in the
      school-age population to direct the programme. The study also investigated risk
      factors for STH infections, including caste, literacy, and defecation and hygiene
      practices, in order to inform the development of complementary interventions.
      METHODS: A cross-sectional survey was conducted among children in 20 schools in
      Bihar. In addition to providing stool samples for identification of STH
      infections, children completed a short questionnaire detailing their usual
      defecation and hand-hygiene practices. Risk factors for STH infections were
      explored. RESULTS: In January-February 2011, 1279 school children aged four to
      seventeen provided stool samples and 1157 children also completed the
      questionnaire. Overall, 68% of children (10-86% across schools) were infected
      with one or more soil-transmitted helminth species. The prevalence of ascariasis,
      hookworm and trichuriasis was 52%, 42% and 5% respectively. The majority of
      children (95%) practiced open defecation and reported most frequently cleansing
      hands with soil (61%). Increasing age, lack of maternal literacy and certain
      castes were independently associated with hookworm infection. Absence of a hand
      washing station at the schools was also independently associated with A.
      lumbricoides infection. CONCLUSIONS: STH prevalence in Bihar is high, and
      justifies mass deworming in school-aged children. Open defecation is common-place
      and hands are often cleansed using soil. The findings reported here can be used
      to help direct messaging appropriate to mothers with low levels of literacy and
      emphasise the importance of water and sanitation in the control of helminths and
      other diseases.

PMID- 25993696
TI  - Transient Blockade of ERK Phosphorylation in the Critical Period Causes Autistic
      Phenotypes as an Adult in Mice.
AB  - The critical period is a distinct time-window during the neonatal stage when
      animals display elevated sensitivity to certain environmental stimuli, and
      particular experiences can have profound and long-lasting effects on behaviors.
      Increasing evidence suggests that disruption of neuronal activity during the
      critical period contributes to autistic phenotype, although the pathogenic
      mechanism is largely unknown. Herein we show that extracellular signal-regulated
      protein kinases (ERKs) play important roles in proper formation of neural
      circuits during the critical period. Transient blockade of ERKs phosphorylation
      at postnatal day 6 (P6) by intraperitoneal injection of blood-brain barrier
      penetrating MEK inhibitor, alpha-[amino[(4-aminophenyl)thio]methylene]-2
      (trifluoromethyl)benzeneacetonitrile (SL327) caused significant increase of
      apoptosis in the forebrain. Furthermore, this induced long-term deleterious
      effects on brain functioning later in adulthood, resulting in social deficits,
      impaired memory and reduced long-term potentiation (LTP). Conversely, blockade of
      ERK phosphorylation at P14 no longer induced apoptosis, nor behavioral deficits,
      nor the reduced LTP. Thus, surprisingly, these effects of ERKs are strongly age
      dependent, indicating that phosphorylation of ERKs during the critical period is
      absolutely required for proper development of brain functioning. This study
      provides novel insight into the mechanistic basis for neurodevelopment disorders:
      various neurodevelopment disorders might be generally linked to defects in ERKs
      signaling during the critical period. 

PMID- 25993699
TI  - A Segmentation Algorithm for Quantitative Analysis of Heterogeneous Tumors of the
      Cervix With 18F-FDG PET/CT.
AB  - As positron-emission tomography (PET) images have low spatial resolution and much
      noise, accurate image segmentation is one of the most challenging issues in tumor
      quantification. Tumors of the uterine cervix present a particular challenge
      because of urine activity in the adjacent bladder. Here, we propose and validate
      an automatic segmentation method adapted to cervical tumors. Our proposed
      methodology combined the gradient field information of both the filtered PET
      image and the level set function into a level set framework by constructing a new
      evolution equation. Furthermore, we also constructed a new hyperimage to
      recognize a rough tumor region using the fuzzy c-means algorithm according to the
      tissue specificity as defined by both PET (uptake) and computed tomography
      (attenuation) to provide the initial zero level set, which could make the
      segmentation process fully automatic. The proposed method was verified based on
      simulation and clinical studies. For simulation studies, seven different
      phantoms, representing tumors with homogenous/heterogeneous-low/high uptake
      patterns and different volumes, were simulated with five different noise levels.
      Twenty-seven cervical cancer patients at different stages were enrolled for
      clinical evaluation of the method. Dice similarity coefficients (DSC) and
      Hausdorff distance (HD) were used to evaluate the accuracy of the segmentation
      method, while a Bland-Altman analysis of the mean standardized uptake value
      (SUVmean) and metabolic tumor volume (MTV) was used to evaluate the accuracy of
      the quantification. Using this method, the DSCs and HDs of the homogenous and
      heterogeneous phantoms under clinical noise level were 93.39 +/-1.09% and 6.02 +/
      1.09 mm, 93.59 +/-1.63% and 8.92 +/-2.57 mm, respectively. The DSCs and HDs in
      patients measured 91.80 +/-2.46% and 7.79 +/-2.18 mm. Through Bland-Altman
      analysis, the SUVmean and the MTV using our method showed high correlation with
      the clinical gold standard. The results of both simulation and clinical studies
      demonstrated the accuracy, effectiveness, and robustness of the proposed method.
      Further assessment of the quantitative indices indicates the feasibility of this
      algorithm in accurate quantitative analysis of cervical tumors in clinical
      practice.

PMID- 25993700
TI  - Obstetric Ultrasound Simulator With Task-Based Training and Assessment.
AB  - The increasing use of point-of-care (POC) ultrasound presents a challenge in
      providing efficient training to POC ultrasound users for whom formal training is
      not readily available. In response to this need, we developed an affordable
      compact laptop-based obstetric ultrasound training simulator. It offers a
      realistic scanning experience, task-based training, and performance assessment.
      The position and orientation of the sham transducer are tracked with 5 DoF on an
      abdomen-sized scan surface with the shape of a cylindrical segment. On the
      simulator, user interface is rendered a virtual torso whose body surface models
      the abdomen of the pregnant scan subject. A virtual transducer scans the virtual
      torso by following the sham transducer movements on the scan surface. A given 3-D
      training image volume is generated by combining several overlapping 3-D
      ultrasound sweeps acquired from the pregnant scan subject using a Markov random
      field-based approach. Obstetric ultrasound training is completed through a series
      of tasks, guided by the simulator and focused on three aspects: basic medical
      ultrasound, orientation to obstetric space, and fetal biometry. The scanning
      performance is automatically evaluated by comparing user-identified anatomical
      landmarks with reference landmarks preinserted by sonographers. The simulator
      renders 2-D ultrasound images in real time with 30 frames/s or higher with good
      image quality; the training procedure follows standard obstetric ultrasound
      protocol. Thus, for learners without access to formal sonography programs, the
      simulator is intended to provide structured training in basic obstetrics
      ultrasound.

PMID- 25993701
TI  - Eight-Week Remote Monitoring Using a Freely Worn Device Reveals Unstable Gait
      Patterns in Older Fallers.
AB  - OBJECTIVES: Develop algorithms to detect gait impairments remotely using data
      from freely worn devices during long-term monitoring. Identify statistical models
      that describe how gait performances are distributed over several weeks. Determine
      the data window required to reliably assess an increased propensity for falling.
      METHODS: 1085 days of walking data were collected from eighteen independent
      living older people (mean age 83 years) using a freely worn pendant sensor
      (housing a triaxial accelerometer and pressure sensor). Statistical distributions
      from several accelerometer-derived gait features (encompassing quantity,
      exposure, intensity, and quality) were compared for those with and without a
      history of falling. RESULTS: Participants completed more short walks relative to
      long walks, as approximated by a power law. Walks less than 13.1 s comprised 50%
      of exposure to walking-related falls. Daily-life cadence was bimodal and step
      time variability followed a log-normal distribution. Fallers took significantly
      fewer steps per walk and had relatively more exposure from short walks and
      greater mode of step-time variability. CONCLUSIONS: Using a freely worn device
      and wavelet-based analysis tools allowed long-term monitoring of walks greater
      than or equal to three steps. In older people, short walks constitute a large
      proportion of exposure to falls. To identify fallers, mode of variability may be
      a better measure of central tendency than mean of variability. A week's
      monitoring is sufficient to reliably assess the long-term propensity for falling.
      SIGNIFICANCE: Statistical distributions of gait performances provide a reference
      for future wearable device development and research into the complex
      relationships between daily-life walking patterns, morbidity, and falls.

PMID- 25993702
TI  - Visual Servoed Three-Dimensional Cell Rotation System.
AB  - Three-dimensional (3-D) positioning and orientation of embryos/oocytes is
      necessary to facilitate micromanipulation tasks such as cell injection and
      cellular structural biopsy commonly performed under a microscope. Conventional
      cell orientation is performed manually by using a vacuum equipped micropipette to
      aspirate and release the cell, which is a trial-and-error approach. The
      conventional method relies heavily on the skill of the operator; it also suffers
      from low precision, low success rate and low controllability. These drawbacks
      illustrate the need for a systematic 3-D cell rotational system to automate the
      cell orientation process. In this paper, we present a noninvasive single cell
      rotation system that can automatically orientate a zebrafish embryo to a desired
      position when both the cytoplasm and the yolk are in the focal plane. A three
      point-contact model for cell rotation that involves a custom-designed rotational
      stage is introduced to provide precise rotational position control. A vision
      recognition algorithm is also proposed to enable the visual servoing function of
      the system. Experimental results show that the proposed system can achieve high
      success rates of 92.5% (x-axis rotation with 40 trails) and 97.5% (about the z
      axis with 80 trails). The system can also successfully complete 3-D cell
      orientation at an average speed of 31 s/cell with a high in-plane rotation
      accuracy of 0.3 ( degrees ) . As a high precise, high controllable and
      deterministic cell manipulating system, it provides a starting point for
      automated cell manipulation for intracytoplasmic sperm injection and embryo
      biopsy for preimplantation genetic diagnosis. 

PMID- 25993703
TI  - A Stochastic Polygons Model for Glandular Structures in Colon Histology Images.
AB  - In this paper, we present a stochastic model for glandular structures in
      histology images of tissue slides stained with Hematoxylin and Eosin, choosing
      colon tissue as an example. The proposed Random Polygons Model (RPM) treats each
      glandular structure in an image as a polygon made of a random number of vertices,
      where the vertices represent approximate locations of epithelial nuclei. We
      formulate the RPM as a Bayesian inference problem by defining a prior for spatial
      connectivity and arrangement of neighboring epithelial nuclei and a likelihood
      for the presence of a glandular structure. The inference is made via a Reversible
      Jump Markov chain Monte Carlo simulation. To the best of our knowledge, all
      existing published algorithms for gland segmentation are designed to mainly work
      on healthy samples, adenomas, and low grade adenocarcinomas. One of them has been
      demonstrated to work on intermediate grade adenocarcinomas at its best. Our
      experimental results show that the RPM yields favorable results, both
      quantitatively and qualitatively, for extraction of glandular structures in
      histology images of normal human colon tissues as well as benign and cancerous
      tissues, excluding undifferentiated carcinomas. 

PMID- 25993704
TI  - Ultra-Low Level Detection of L-Histidine Using Solution-Processed ZnO Nanorod on
      Flexible Substrate.
AB  - This work demonstrates a novel label free and sensitive approach for the
      detection of L-histidine. This is a simple and reliable method for ultra-low
      level detection of L-histidine. All solution processed synthesizing technique was
      utilized to develop such type of detection scheme. Silicon substrate was replaced
      by normal transparent sheet to make it more facile and cost-effective detection
      technique. Fabricated device for L-histidine detection works upon the variation
      of current through the ZnO nanorod with L-histidine concentration. Operation
      principle strongly depends upon the electron charge transfer between metal cation
      and L-histidine inside the chelating complex. Morphological, structural and
      optical characterization of solution processed synthesized ZnO nanorod (ZnO NR)
      was carried out prior to sensor device fabrication. Our sensor device exhibits
      the sensitivity around 0.86 nA/fM and lower limit of detection (LOD) ~ 0.1
      fM(S/N=3).

PMID- 25993705
TI  - Oscillometric Blood Pressure Estimation: Past, Present, and Future.
AB  - The use of automated blood pressure (BP) monitoring is growing as it does not
      require much expertise and can be performed by patients several times a day at
      home. Oscillometry is one of the most common measurement methods used in
      automated BP monitors. A review of the literature shows that a large variety of
      oscillometric algorithms have been developed for accurate estimation of BP but
      these algorithms are scattered in many different publications or patents.
      Moreover, considering that oscillometric devices dominate the home BP monitoring
      market, little effort has been made to survey the underlying algorithms that are
      used to estimate BP. In this review, a comprehensive survey of the existing
      oscillometric BP estimation algorithms is presented. The survey covers a broad
      spectrum of algorithms including the conventional maximum amplitude and
      derivative oscillometry as well as the recently proposed learning algorithms,
      model-based algorithms, and algorithms that are based on analysis of pulse
      morphology and pulse transit time. The aim is to classify the diverse underlying
      algorithms, describe each algorithm briefly, and discuss their advantages and
      disadvantages. This paper will also review the artifact removal techniques in
      oscillometry and the current standards for the automated BP monitors. 

PMID- 25993706
TI  - Effective Discriminative Feature Selection With Nontrivial Solution.
AB  - Feature selection and feature transformation, the two main ways to reduce
      dimensionality, are often presented separately. In this paper, a feature
      selection method is proposed by combining the popular transformation-based
      dimensionality reduction method linear discriminant analysis (LDA) and sparsity
      regularization. We impose row sparsity on the transformation matrix of LDA
      through l2,1-norm regularization to achieve feature selection, and the resultant
      formulation optimizes for selecting the most discriminative features and removing
      the redundant ones simultaneously. The formulation is extended to the l2,p-norm
      regularized case, which is more likely to offer better sparsity when 0 < p < 1.
      Thus, the formulation is a better approximation to the feature selection problem.
      An efficient algorithm is developed to solve the l2,p-norm-based optimization
      problem and it is proved that the algorithm converges when 0 < p <= 2.
      Systematical experiments are conducted to understand the work of the proposed
      method. Promising experimental results on various types of real-world data sets
      demonstrate the effectiveness of our algorithm.

PMID- 25993707
TI  - Undamped Oscillations Generated by Hopf Bifurcations in Fractional-Order
      Recurrent Neural Networks With Caputo Derivative.
AB  - In this paper, a fractional-order recurrent neural network is proposed and
      several topics related to the dynamics of such a network are investigated, such
      as the stability, Hopf bifurcations, and undamped oscillations. The stability
      domain of the trivial steady state is completely characterized with respect to
      network parameters and orders of the commensurate-order neural network. Based on
      the stability analysis, the critical values of the fractional order are
      identified, where Hopf bifurcations occur and a family of oscillations bifurcate
      from the trivial steady state. Then, the parametric range of undamped
      oscillations is also estimated and the frequency and amplitude of oscillations
      are determined analytically and numerically for such commensurate-order networks.
      Meanwhile, it is shown that the incommensurate-order neural network can also
      exhibit a Hopf bifurcation as the network parameter passes through a critical
      value which can be determined exactly. The frequency and amplitude of bifurcated
      oscillations are determined. 

PMID- 25993708
TI  - Reflections from ACC 2015.

PMID- 25993709
TI  - The impact of cytochrome P450 2C19 polymorphism on the occurrence of one-year in
      stent restenosis in patients who underwent percutaneous coronary intervention: A
      case-match study.
AB  - OBJECTIVE: In this case-match study, we evaluated the impact of the CYP2C19*2
      polymorphism in the occurrence of in-stent restenosis during a 1-year follow-up
      period despite adequate dual anti-platelet therapy in Iranian patients having
      undergone percutaneous coronary intervention (PCI). METHODS: This study,
      conducted at a tertiary referral heart center in Tehran, recruited 100 patients:
      50 patients had in-stent restenosis after PCI during a 1-year follow-up and were
      compared to another 50 patients without in-stent restenosis who were individually
      matched according to sex. In order to evaluate the impact of the CYP2C19*2
      polymorphism, case frequency matching was performed with respect to variables
      previously shown to be predictors of in-stent restenosis. The CYP2C19*2
      polymorphism evaluated using real-time PCR methods. RESULTS: Among all 100
      patients (mean age=60.09 +/- 10.29: 72.0% male), 89 (89%) patients had wild
      (CYP2C19*1/CYP2C19*1) and 11% had a heterozygous (CYP2C19*1/CYP2C19*2) genotypes,
      and there was no patient with a completely mutant genotype (CYP2C19*2/CYP2C19*2).
      Conditional logistic regression analysis showed that there was no significant
      association between genotype CYP2C19*1/CYP2C19*2 and the occurrence of in-stent
      restenosis after PCI (OR=2.5, p value=0.273). CONCLUSION: Our findings indicated
      that carrying a CYP2C19*2 allele with a functional CYP2C19*1 allele had no
      significant association with in-stent restenosis 1 year after PCI. The
      antiplatelet treatment strategy for non-functional allele carriers is still a
      matter of controversy. Further studies with larger sample sizes are necessary to
      determine the prevalence of non-functional alleles in various populations and to
      achieve a consensus about the effective treatment strategy.

PMID- 25993710
TI  - The impact of cytochrome P 450 2 C19 polymorphism on the occurrence of 1-year in
      stent restenosis in patients who underwent percutaneous coronary intervention: A
      case-match study.

PMID- 25993711
TI  - Epicardial adipose tissue: Just a predictor or a local player for coronary
      atherosclerosis?

PMID- 25993712
TI  - Searching for the key to improve infarcted cardiac wall motion and prevent
      ventricular remodeling after ST-segment elevation myocardial infarction: Beyond
      symptom-onset-to-balloon time.

PMID- 25993713
TI  - Spontaneous coronary artery dissection: Case series from two institutions with
      literature review.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary
      syndrome (ACS). Consequently, its presentation and optimal treatment are yet to
      be clearly defined. In the current literature, all case series report less than
      50 patients, most of whom are either young peripartum women or women who have
      used oral contraceptives over long periods. All information in this study was
      compiled by the database service from two hospitals, the first one between 2003
      and 2012 and the second one between 2007 and 2012, to include the clinical
      characteristics, angiography. and treatment approaches in the study population.
      The study population consisted in four women (50%) and four men (50%) whose ages
      ranged between 28 and 57 years. Two women had a history of oral contraceptive use
      and three women presented during peripartum. None of the patients had traditional
      cardiovascular risk factors or previous heart disease. In 88% of the cases, the
      principal diagnoses were non-ST segment elevation myocardial infarction and
      unstable angina. All patients underwent emergency coronary angiography and
      percutaneous coronary intervention. Half of them were treated with drug-eluting
      stents and the other half with bare metal stents. The most frequent type of
      dissection was NIHBL Type E, and the right coronary artery was the most
      frequently compromised. SCAD is a rare cause of ACS; however, its identification
      has improved due to the availability of angiography and new complementary
      techniques. Regarding treatment, PCI seems effective with adequate long-term
      results. 

PMID- 25993714
TI  - How do we measure epicardial adipose tissue thickness by transthoracic
      echocardiography?
AB  - Epicardial adipose tissue (EAT) is a component of the visceral adiposity located
      between the heart and pericardium. It is associated with certain diseases, such
      as metabolic syndrome, coronary artery disease, and hypertension. Therefore,
      measurement of EAT thickness has recently gained importance. Examination by
      transthoracic echocardiography for measuring EAT thickness is preferable because
      of easy availability and low cost. The present review focuses on the method of
      measuring EAT thickness by transthoracic echocardiography as well as the issues
      of concern. 

PMID- 25993715
TI  - Right ventricular ischemic insult: A comprehensive protocol with cardiovascular
      magnetic resonance.

PMID- 25993716
TI  - Apical systolic flow within the left ventricle: A novel and simple Doppler
      parameter in prediction of mitral regurgitation severity.

PMID- 25993717
TI  - Short-long-short sequence-induced torsade de pointes after transcatheter aortic
      valve implantation.

PMID- 25993718
TI  - Elizabethkingia meningosepticum endocarditis: A rare case and special therapy.

PMID- 25993719
TI  - New technique for challenging cases of percutaneous balloon mitral valvuloplasty:
      The venoarterial looping.

PMID- 25993720
TI  - Hypotension, tachycardia, and tachypnea in a patient with coronary artery
      disease.

PMID- 25993721
TI  - Methods to increase clinical applicability of heart rate variability analysis for
      noninvasive detecting severity of coronary lesions in patients with coronary
      heart disease.

PMID- 25993722
TI  - Obesity and coronary bypass.

PMID- 25993723
TI  - Noncompaction with dysmorphism, mental retardation, general wasting, and
      hypogonadism requires neurologic and sophisticated cytogenetic investigations.

PMID- 25993724
TI  - Thrombus formation during septal puncture.

PMID- 25993725
TI  - Noninvasive cardiac imaging for the diagnosis of coronary artery disease in
      women.

PMID- 25993726
TI  - Epicardial fat and coronary artery disease: An open debate.

PMID- 25993727
TI  - The detection of cardiac tamponade by hemodynamic transesophageal
      echocardiography after left ventriculer assist device implantation.

PMID- 25993728
TI  - How can we forget our mentor Prof. Baki!

PMID- 25993729
TI  - An unusual image of Vieussens' arterial ring communicating with the pulmonary
      artery.

PMID- 25993730
TI  - Bicuspid aortic valve and extremely elongated chordae tendineae protruding into
      the left ventricular outflow tract.

PMID- 25993731
TI  - Combination of tetralogy of Fallot with absent pulmonary valve and left pulmonary
      artery originating from patent ductus arteriosus: A rare association in an
      infant.

PMID- 25993732
TI  - Imaging the posterior mediastinum: a multimodality approach.
AB  - The posterior mediastinum contains several structures that can produce a wide
      variety of pathologic conditions. Descending thoracic aorta, esophagus, azygos
      and hemiazygos veins, thoracic duct, lymph nodes, adipose tissue, and nerves are
      all located in this anatomical region and can produce diverse abnormalities.
      Although chest radiography may detect many of these pathologic conditions,
      computed tomography and magnetic resonance are the imaging modalities of choice
      for further defining the relationship of posterior mediastinal lesions to
      neighboring structures and showing specific imaging features that narrow the
      differential diagnosis. This review emphasizes modality-related answers to
      morphologic questions, which provide precise diagnostic information. 

PMID- 25993733
TI  - Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac
      arrest are associated with multiple organ dysfunction syndrome and early death.
AB  - BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary
      resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3)
      and soluble suppression of tumorigenicity 2 (sST2), in comparison with the
      classic high-sensitivity C-reactive protein (hsCRP), for prediction of early
      multiple organ dysfunction syndrome (MODS), early death, and long-term outcome
      after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed
      at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non
      neurological Sequential Organ Failure Assessment (SOFA) score >= 12. Intensive
      care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were
      evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48%
      had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission,
      median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1
      ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in
      patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were
      also higher in patients who died in ICU and in those with an unfavorable 12-month
      neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were
      independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340,
      (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and
      1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were
      independently associated with ICU death. CONCLUSIONS: Higher plasma levels of
      PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher
      risk of MODS and early death.

PMID- 25993734
TI  - Laboratory biomarkers and frailty: presentation of the FRAILOMIC initiative.

PMID- 25993735
TI  - [Preliminary results of fetal fibronectin testing in twin pregnancies].
AB  - OBJECTIVES: Purpose of this study is to investigate accuracy of fetal fibronectin
      testing (fFN test) as a means to predict preterm birth in twin gestations without
      symptoms of preterm labour as well as to compare the results with the world
      trends. MATERIAL AND METHODS: This study is prospective and comparative. It
      covers a period from December 2012 to May 2013, includes a total of 43 twin
      pregnancies--34 bichoriotic biamniotic twin pregnancies, 6 monochoriotic
      biamniotic twin pregnancies and 3 monochoriotic monoamniotic twin pregnancy A
      measurement of cervical length by transvaginal ultrasonography is used as well.
      RESULTS: A total of 43 women had cervico-vaginal fetal fibronectin testing
      obtained from 24 to 34 weeks of gestation. 31 women had negative fFN test and 12
      had positive results. In patiens with negative testing delivery began after a
      period of 30 days average. In most of the women with negative test result labour
      occurred after more than 14 days, which means that the test has high specificity.
      Patients with positive test result had delivery after a mean period of 12 days,
      which demonstrated that the fetal fibronectin test has high sensitivity The
      shortest period between the positive testing and delivery was one day A
      transvaginal ultrasound measurement of the cervical length was performed. Four of
      our patients had positive test result as well as short cervix and delivery
      occurred at a mean age of 31 w.g. and 5 days after the test. Four women tested
      positive for fFNA and had normal cervical length. They had labour at 35+3 w.g.
      and 23 days after the test. Eight patients tested negative for fFN and had short
      cervical length, but they had labour after 28 days as well. Most of the
      researched women (19) had negative test result and normal cervical length and
      they delivered after average 30 days. CONCLUSIONS: Fetal fibronectin testing used
      in twin pregnancies as well as in singleton pregnancies proves to have high
      specificity sensitivity, good positive and negative predictive value. It offers
      the opportunity for adequate tocolytic therapy once the test comes out to be
      positive. There is a posibility to decrease the use of corticosteroids. The
      length of stay in the hospital can also be reduced.

PMID- 25993737
TI  - [Factors affecting duration of the laparoscopic myomectomy].
AB  - Laparoscopic myomectomy (LM) has been an alternative to abdominal myomectomy in
      cases of subserosal and intramural myomas since 1990. In the literature less
      attention is paid to the factors responsible for the length of the surgical time
      of the LM. Our study comprehends 66 patients underwent laparoscopic myomectomy
      for one or more intramural myomas with size > 5 sm. In order to evaluate the
      factors that are responsible for the duration of the procedure we survey the
      following indicators: age, BMI, year of the operation, previous abdominal
      operations, way of delivery, size, number and localization of the myomas. Our
      results show that statistically significant effect for the duration of LM have
      the yearof the operation, numberof the myomas and their localization in the
      uterine wall. Significantly longer operative time is detected in 2012 (133.57 +/-
      17,805 min.) and the shorter time was in 2014 (66.67 +/- 20, 237 min.) (P <
      0.05). We established statistically significant relation between the number of
      the myomas and duration of the operation (P=0.023). The analysis of the indicator
      localization of the myomas shows that myomas in the anterior uterine wall are
      with shortest average surgical time--90.5 +/- 33, 321 min., next are these in the
      posterior uterine wall--93.81+/- 39, 176 min. Myomas in the fundus of the uterus
      have longest average surgical time--115.83 +/- 35, 253 min.

PMID- 25993736
TI  - [Pregnancy outcome in women over the age of 35].
AB  - AIM: To assess pregnancy outcome in women aged > or =35, followed prospectively,
      and the relation between maternal age and the incidence of abortions after 12 gw
      (spontaneous and medical), preterm delivery, mode of delivery and congenital
      anomalies. MATERIALS AND METHODS: 495 women from the Fetal Medicine Clinic of the
      State University Hospital "Maichin Dom" in Sofia were enrolled in the study
      between 02/2012 and 02/2014 with gestational age > or =12 completed weeks. The
      patients were devided in 3 groups according to age-- < or =34, between 35 and 39
      and > or = 40 years of age. Pregnancy outcome was veirified from hospital records
      and phone intenrviews with the patients themselves. Data were processed with SPSS
      13.0 statistical package. Descriptive and comparative analysis was performed
      after grouping according to one or more characteristics; p values <0.05 were
      considered as evidence of statistical significance for tested effects. RESULTS:
      131/495 (26.5%) of the patients were < or =34 years of age, 254/495 (51.3%) were
      between 35 and 39 and 110/495 (22.2%) were > or =40 years of age. Maternal age >
      or =35 was associated with statistically significant increase of the total late
      abortion rate (spontaneous and medical abortions)--from 6.9% for those < or =34
      yars of age to 11.3%--for the ones between 35-39 and 11.4%--for the ones > or =40
      years. There was also statistically significant increase in the incidence of late
      medical abortions in the group > or =40 years of age (p=0.011). It was 2/124
      (1.6%) for the group aged < or =34, 7/230 (3%)--in the group aged 35-39 and 9/100
      (9.0%)--in the group > or =40 years of age. The difference in late spontaneous
      abortions rate was not statistically significant among the groups. There was
      statistically significant increase in the incidence of preterm deliveries
      (spontaneous and induced)--14/131 (10.7%) in the group aged < or =34, 52/208
      (25.0%)--in the group between 35-39 and 20/93 (21.5%)--in the group > or =40
      years of age (p=0.013). There was also a significant increase in Cesarean section
      rate with age--from 44/131 (33.6%) in the group < or =34, to 139/254 (54.7%)--in
      the group between 35-39, and 69/110 (62.7%)--in the group > or =40 years
      (p=0.0001). There is a tendency for increased operative vaginal delivery rate
      with age; however the difference is not statistically significant, probably due
      to the small number of cases (p=O. 113). There was also statistically significant
      increase in the proportion of newborns with congenital anomalies in women > or
      =40 years of age (p=0.005)--from 1/131 (0.8%) in patients < or =34, to 2/254
      (1.0%) for those between 35 and 39, and 6/110 (5.5%)--for those > or =40 years.
      Part of the congenital anomalies was prenatally diagnosed chromosomal defects
      without termination of pregnancy CONCLUSIONS: Maternal age > or =35 years is
      associated with statistically significant increase in late medical abortions,
      preterm delivery and Cesarean section rate and congenital fetal anomalies.

PMID- 25993738
TI  - [Prenatal diagnosis and treatment of twin-to-twin transfusion syndrome].
AB  - Monochorionic twins originate of single placenta serving two twins, which
      potentionally could lead to unique complications including twin-to-twin
      transfusion syndrome, twin anemia--polycythemia sequence (TAPS), selective
      intrauterine growth restriction or twin reversed arterial perfusion sequence
      (TRAP). A shared placenta and fetoplacental circulation are responsible for
      significant discordance in amniotic fluid, fetoplacental hemodynamics, fetal size
      or fetal structural defects. All these complications pose high risk of fetal
      demise in one of the twins and therefore this could trigger death or neurological
      injury of the co-twin. The most severe complication of the monochorionic
      placenation is twin-to-twin transfusion syndrome. CONCLUSION: Prenatal management
      of complicated monochorionic twin pregnancy with twin-to-twin transfusion
      syndrome exposed to the risk of losing one or two twins in utero justifies the
      endoscopic laser coagulation for placental anastomoses as a first line treatment.

PMID- 25993739
TI  - [Mastodynia. Premenstrual syndrome].
AB  - Mastodynia is defined as breast tenderness and pain, also called mastalgia. There
      are several types of cyclic, noncyclic and extramammary. The cyclic mastodynia is
      the most common one, and represents a clinical symptom of the premenstrual
      syndrome and of the more severe premenstrual dysphoric disorder. The article
      outlines different types of mastalgia with their typical clinical features,
      including the relatively rear Tietze's syndrome and MONDOR'S disease, as well as
      the PMS and the PMDD. The authors also offer a diagnostic algorithm and specific
      diagnostic criteria. There is also a discussion on the main treatment
      alternatives being symptomatic treatment of the most troublesome symptoms or
      alteration of the menstrual cycle and a brief discussion on the pharmaceutical
      preparations used for treatment including the administration of selective
      serotonin reuptake inhibitors (SSRI).

PMID- 25993740
TI  - [Risky factors in ovarian cancer (our and foreign experience)].
AB  - AIM: Our aim was to summarize our and foreign experience and evaluate and
      research the most common risky factors for development of ovarian cancer. In this
      way we wanted to summarize also the prevanantive factors for ovarian cancer.
      MATERIAL AND METHODS: We researched for 10 years period patients with ovarian
      cancer (2000 patients). The most common risky factors were examined and
      researched. RESULTS: All patients with ovarian, tube and peritoneall cancer--must
      be tested for BRCA 1 and BRCA2 gene mutations. The patients who want to preserve
      their reproductive functions orto postpone the preventive surgery, have to go
      through 6 months screening by TVS. The patients with Lynch Syndrome are advised
      for prophylactic salpingoophorectomy or hysterectomy. When there was a high risk
      the patients are advised to take oral contraceptives before family planning.
      CONCLUSION: Nevertheless these results future research and clinical trials will
      give additional light in this field.

PMID- 25993741
TI  - [Visceral metastases of triple negative breast cancers with contribution of cases
      and review of the literature].
AB  - Breast carcinoma is a heterogeneous disease. Clinical treatment of metastases
      from triple negative-Estrogen receptor-(ER(-), Progesterone receptor (PgR)(-),
      Human epidermal growth factor receptor 2(HER2)(-)) primary breast cancer and
      metachronous second cancer in visceral organs is different. In this article we
      report two cases of visceral metastases from two patients with Stage IV triple
      negative primary breast cancer. We presented morphology findings and
      immunophenotype of all lesions and we offered a practical recommendation for
      diagnosis of similar cases.

PMID- 25993742
TI  - [Significance of the clinical and dermatoscopic findings, histopathology and
      reflex confocal microscopy (RCM) in determining the origin of melanocytic
      lesions: an analysis based on a clinical case].
AB  - Dysplastic nevi (DN) are pigmented lesions combining the features of typical
      nevomelanocytic nevi, as well as some of the clinical and histological
      characteristics of malignant melanoma (MM). DN are associated with an increased
      risk of developing a MM. The genetic predisposition and intensive sun exposure
      are some of the main etiologic factors for their evolution. The clinical and the
      dermatoscopic findings may be misleading in the estimation of the diagnosis of
      malignant melanoma or a dysplastic nevus. Precisely because of this fact, the
      determination of the optimal treatment plan for each individual patient could be
      a challenge. The confocal microscopy is one of the new methods that is capable to
      contribute in a high percentage of the cases for this precise differentiation.
      Unfortunately, its application is not widespread, and the methodology is labor
      intensive and additional training and qualification are required. We present a
      case of a female patient with DN in which clinical and dermatoscopic findings
      were speaking rather in favor of malignant melanoma but after the subsequent
      surgical excision, the histopathological evaluation rejected this doubt,
      definitively. In cases of lesions with difficult location for surgical treatment
      and unclear clinical and dermatoscopic findings, reflex confocal microscopy (RCM)
      could be a possible elegant solution which prevents of stigmatization of the
      patients from different multiple and often unnecessary surgical approaches.

PMID- 25993743
TI  - [Coronary angiography of in vitro porcine heart using MSCT].
AB  - OBJECTIVE: To establish standardized methods and parameters of the isolated heart
      coronary angiography through the experiment of in vitro porcine heart by MSCT.
      METHODS: Based on different perfusion volume (50, 60 and 70 mL) and different
      perfusion-imaging time (5, 10 and 20 min), the in vitro porcine coronary artery
      was injected liposoluble and water-soluble contrast agents using remodel
      angiography equipment and scanned by MSCT. And the 3D image results were
      compared. The images were recorded and evaluated by 2 radiologists and analyzed
      by statistical software. RESULTS: Liposoluble contrast agent affected the images
      by damaging and infiltrating the fats around the coronary artery, while the water
      soluble contrast agent didn't affect the images. The groups with 60 mL or 70 mL
      perfusion and 5 min perfusion-imaging time had the best images. CONCLUSION: The
      suitable parameters of the angiography lay the foundation of postmortem coronary
      angiography.

PMID- 25993744
TI  - [A review on the research progress of the computer-aided detection of pulmonary
      nodule].
AB  - Computer-aided detection (CAD) of pulmonary nodule technology can effectively
      assist the radiologist to enhance lung nodule detection efficiency and accuracy
      rate, so it can lay the foundation for the early diagnosis of lung cancer. In
      order to provide reference for the scholars and to develop the CAD technology, we
      in this paper review the technology research and development of CAD of the
      pulmonary nodules which is based on CT image in recent years both home and
      abroad. At the same time, we also analyse the advantages and shortcomings of
      different methods. Then we present the improvement direction for reference.
      According to the literature in recent years, there still has been large
      development space in CAD technology for pulmonary nodules. The establishment and
      improvement of the CAD system in each step would be of great scientific value.

PMID- 25993745
TI  - [Bloodstream infections in southwestern China: 2012 Whire Union report on
      bacterial susceptibility to antibiotics].
AB  - OBJECTIVE: To test the susceptibility of blood culture isolates to antibiotics in
      a sample of hospitals in Southwestern China in 2012. METHODS: Blood culture
      samples were taken and tested from the patients under the Whire Union
      surveillance in three tertiary hospitals in Southwestern China in 2012. We
      performed antimicrobial susceptibility analyses on the blood culture isolates
      using WHONET5. 5 and SPSS19.0. RESULTS: A total of 1745 isolates were identified:
      877 Gram-positive (50.26%); 868 Gram-negative (49.74%). Coagulase-negative
      Staphylococcius (CNS, 541 strains, 31.00%), Escherichia coli (ECO, 379 strains,
      21.72%), Klebsiella spp. (170 strains, 9.74%), Enterococcus spp. (143 strains,
      8.20%) and Staphylococcus aureus (SAU, 128 strains, 7.34%) comprised the majority
      of isolates. Methicillin-resistant was found in 37.5% of S. aureus and 85.4% of
      CNS, respectively. Zero and 6.3% resistance to vancomycin were found for
      Enterococcus faecalis and E. faecium, respectively,compared with a 1.4% and 7.9%
      resistance to linezolid, respectively. Imipenem-resistance occurred in 0.7% E.
      coli, 3.6% Klebsiella spp., and 11.1% Enterobacter spp.. Nonfermenters were
      highly resistant to carbapenems, with an imipenem resistance rate of 25.0% in P.
      aeruginosa and 79.1% in Acinetobacter baumannii. Antimicrobial usage and critical
      care units were identified as risk factors for MRSA and multi-drug-resistant A.
      baumannii infections. Patients undergoing tracheotomy/endotracheal intubation
      were likely to develop multi-drug-resistant A. baumannii infections than others.
      CONCLUSION: CNS, E. coli,Klebsiella spp., Enterococcus spp. and S. aureus were
      the predominant organisms in bloodstream infections in Southwestern China. Low
      methicillin-resistant rate was found in Staphylococcus aureus. But vancomycin
      resistant rate was high in E. faecium. Imipenem-resistant rates varied in
      Enterobacteriaceae: higher in non-fermenting bacteria especially in Acinetobacter
      spp. Use of abtimicrobial drugs and invasive procedures can lead to development
      of antimicrobial drugs-resistance.

PMID- 25993746
TI  - Ophidiomyces ophiodiicola dermatitis in eight free-ranging timber rattlesnakes
      (Crotalus horridus) from Massachusetts.
AB  - Eight free-ranging timber rattlesnakes (Crotalus horridus) from two
      geographically isolated Massachusetts populations were observed with skin lesions
      located primarily on the head but occasionally also on the lateral and ventral
      surfaces of the body. The snakes underwent health assessments that included
      physical examination, clinical pathology, full body radiographs, and full
      thickness biopsies of skin lesions. Each snake had fungal elements present
      histologically in tissue sections from skin lesions. Ophidiomyces ophiodiicola
      was identified from skin lesions using polymerase chain reaction in all eight
      snakes.

PMID- 25993747
TI  - Fluid-structure interaction analysis of pulsatile flow within a layered and
      stenotic aorta.
AB  - In this paper, the hemodynamic characteristics of blood flow and stress
      distribution in a layered and stenotic aorta are investigated. By introducing
      symmetrical and unsymmetrical stenosis, the influence of stenosis morphology and
      stenotic ratio on the coupled dynamic responses of aorta is clarified. In the
      analysis, the in-vivo pulsatile waveforms and fully fluid-structure interaction
      (FSI) between the layered elastic aorta and the blood are considered. The results
      show that the fluid domain is abnormal in the stenotic aorta, and the whirlpool
      forms at the obstructed and downstream unobstructed regions. The maximum wall
      shear stresses appear at the throat of the stenosis. Downstream region appears
      low and oscillated shear stresses. In addition, along with the increase of the
      stenotic ratio, the amplitude of the maximum shear stress will be intensively
      increased and localized, and the sensitivity is also increased. In the aorta with
      unsymmetrical stenosis, the Von Mises stresses reach the peak value at the side
      with the surface protuberance, but they are reduced at the side with no
      protuberance. The sign variation of the layer interface shear stresses near the
      throat indicates the variation of the shear direction which increases the
      opportunity of shear damage at the transition plane. Moreover, the shear stress
      levels at the fluid-solid and intima-media interfaces are higher than that at the
      media-adventitia interface. The unsymmetrical stenosis causes higher stresses at
      the side with the surface protuberance than symmetrical one, but lower at the
      side with no protuberance. These results provide an insight in the influence of
      the stenosis, as well as its morphology, on the pathogenesis and pathological
      evolution of some diseases, such as arteriosclerosis and aortic dissection.

PMID- 25993748
TI  - Bilateral congenital cholesteatoma of the temporal bone in Crouzon syndrome.
AB  - INTRODUCTION: Crouzon syndrome is an autosomal dominant genetic disease
      characterized by bicoronal craniosynostosis, exorbitism with hypertelorism, and
      maxillary hypoplasia with mandibular prognathism. CASE OUTLINE: We present the
      first reported case of Crouzon syndrome associated with a bilateral con- genital
      cholesteatoma of the temporal bone and discuss about the potential pathogenesis.
      CONCLUSION: Early diagnosis and management are crucial to prevent complications
      and an otologist should be an integral part of the multidisciplinary team.

PMID- 25993749
TI  - Marriage, intimacy and risk of HIV infection in south west Uganda.
AB  - Long-term, monogamous, relationships are often portrayed as protective in HIV
      prevention campaigns. Focusing on marriage in a community in south west Uganda,
      we examine why and how people enter long term relationships, what their
      expectations are and what factors sustain those relationships. Qualitative data
      were collected using in-depth interviews with 50 men and women randomly selected
      from a General Population Cohort. The results showed that managing expectations
      to sustain marriage is challenging; however the socio-economic and cultural
      benefits of marriage: having children, property acquisition as well as securing
      societal status tend to overshadow the costs associated with risks from
      infidelity such as sexually transmitted infections (including HIV). Recognising
      the compromises that couples may make to sustain their marriage is an important
      step towards acknowledging that 'being faithful' may be about staying together
      and showing commitment, not sexual exclusivity.

PMID- 25993750
TI  - [Vocal cord paralysis associated with tracheal intubation: incidence, risk
      analysis, and classification of severity].
AB  - Vocal cord paralysis after tracheal intubation is rare. It causes severe
      hoarseness and aspiration, and delays recovery and discharge. Arytenoid cartilage
      dislocation and recurrent nerve paralysis are main causes of vocal cord
      paralysis. Physical stimulation of the tracheal tube as well as patient and
      surgical characteristics also contribute. Vocal cord paralysis occurs in 1
      (0.07%) of 1,500 general surgery patients and on the left side in 70% of cases.
      It is associated with surgery/anesthesia time (two-fold, 3-6 hours; 15-fold, over
      6 hours), age (three-fold, over 50 years), and diabetes mellitus or hypertension
      (two-fold). Symptoms resolve in 2-3 months. In adult cardiovascular surgery,
      vocal cord paralysis occurs in 1 (0.7-2%) of 50-100 cardiac surgery patients and
      1 (8.6-32%) of 3-10 thoracic aortic surgery patients. In pediatric cardiac
      surgery, vocal cord paralysis occurs in 1 (0.1-0.5%) of 200-1,000 patients. We
      classified the severity of vocal cord paralysis as I, severe hoarseness; II,
      aspiration or dysphagia; and III, bilateral vocal cord paralysis, aspiration
      pneumonia, or the need for tracheal re-intubation or tracheotomy. We discuss the
      importance of informed consent for the patient and family.

PMID- 25993751
TI  - Successful acupuncture treatment of uterine myoma.
AB  - Our case report as the second one in the medical literature demonstrated
      successful outcome of acupuncture treatment of uterine myoma in terms of tumor
      size reduction and absence of hypermenorrhea and anemia with successful perinatal
      outcome with two healthy newborns after previous late miscarriage. Accordingly,
      acupuncture treatment can be used as an inexpensive, efficient and simple
      therapeutic option in the management of particular types of myoma.

PMID- 25993752
TI  - [Caries status of the first permanent molar among 7- to 9-year-old children in
      Tangshan city and their correlation].
AB  - OBJECTIVE: This study aims to investigate the caries status of the first
      permanent molar and primary tooth among 7- to 9-year-old children in Tangshan
      city and the correlation between caries of primary tooth and the first permanent
      molar. METHODS: A stratified cluster sampling method was used on the basis of the
      Basic Approach of Oral Health Survey of WHO and the Guideline of the Third
      National Oral Health Survey. A total of 10 primary schools were randomly sampled
      in clusters that included 51 primary school sampling spots in Tangshan. The
      caries status of 1 794 children aged 7 years to 9 years was examined. RESULTS:
      The prevalence rate of the first permanent molar caries was 47.49% (852/1 794),
      the mean number of DMFT was 1.30 +/- 1.59, the mean number of DMFS was 1.96 +/-
      3.40, and the filling rate was only 2.35% (20/852). The preva- lence rate and
      mean DMFT of the first permanent molar caries showed significant difference
      between different ages and genders (P < 0.05). However, the mean DMFS of the
      first permanent molar caries only showed significant difference between the
      various ages (P < 0.05). The prevalence rate of the primary tooth caries was
      83.11% (1 491/1 794), the mean number of dmft was 4.82 +/- 3.55, the mean number
      of dmfs was 6.51 +/- 5.61, and the filling rate was 12.41% (185/1 491). Caries of
      primary tooth was the first permanent molar caries risk factor [r = 0.277, OR =
      5.736, P = 0.00, 95% CI (4.175, 7.881)]. Significant correlation was found
      between the caries of primary tooth and first permanent molar (r = 0.274, P <
      0.001). CONCLUSION: Caries status of the first permanent molar among 7- to 9-year
      old children in Tangshan city is serious. Caries status of primary tooth may play
      an important role in predicting the first permanent molar caries in clinic and
      prevention.

PMID- 25993753
TI  - [Effect of total saponins from rhizoma dioscoreae nipponicae on the expression of
      SDF1 and HCIKB kinase in rIK-1beta induced fibroblast-like synoviocytes].
AB  - OBJECTIVE: To study the effect of total saponins from Rhizoma Dioscoreae
      nipponicae (RDN) on the expression of stroma cell derived factor 1 (SDF1) and IKB
      kinase (IKK) in rIL-1beta induced fibroblast-like synoviocytes (FLS). METHODS:
      FLS were primarily cultured and the 3rd generation log phase growth FLS were
      divided into the normal control group, the model group, and the medication group.
      10 microg/L rIL-1beta was used to induce the proliferation of FLS in the model
      group.10 microg/L rIL-1beta and 100 microg/L RDN were administered to co-incubate
      FLS in the medication group. No treatment was given to FLS in the normal control
      group. Expression levels of SDF1 and IkapaB kinase proteins (p-IKK) were detected
      using Western blot. RESULTS: Expression levels of SDF1 and p-IKK increased
      significantly higher in the model group than in the normal control group
      (P<0.01). Compared with the model group, expression levels of SDF-1 and p-IKK
      significantly decreased in the medication group (P <0.01). CONCLUSIONS: Total
      saponins from RDN could inhibit the activation of both SDF1 and p-IKK. It might
      further regulate the expression of IKB kinase by regulating the expression of
      SDF1.

PMID- 25993754
TI  - Management of acute malnutrition in infants aged under 6 months (MAMI): current
      issues and future directions in policy and research.
AB  - BACKGROUND: Globally, some 4.7 million infants aged under 6 months are moderately
      wasted and 3.8 million are severely wasted. Traditionally, they have been over
      looked by clinicians, nutritionists, and policy makers. OBJECTIVE: To present
      evidence and arguments for why treating acute malnutrition in infants under 6
      months of age is important and outline some of the key debates and research
      questions needed to advance their care. METHODS: Narrative review. RESULTS AND
      CONCLUSIONS: Treating malnourished infants under 6 months of age is important to
      avoid malnutrition-associated mortality in the short-term and adverse health and
      development outcomes in the long-term. Physiological and pathological differences
      demand a different approach from that in older children; key among these is a
      focus on exclusive breastfeeding wherever possible. New World Health Organization
      guidelines for the management of severe acute malnutrition (SAM) include this age
      group for the first time and are also applicable to management of moderate acute
      malnutrition (MAM). Community-based breastfeeding support is the core, but not
      the sole, treatment. The mother-infant dyad is at the heart of approaches, but
      wider family and community relationships are also important. An urgent priority
      is to develop better case definitions; criteria based on mid-upper-arm
      circumference (MUAC) are promising but need further research. To effectively move
      forward, clinical trials of assessment and treatment are needed to bolster the
      currently sparse evidence base. In the meantime, nutrition surveys and screening
      at health facilities should routinely include infants under 6 months of age in
      order to better define the burden and outcomes of acute malnutrition in this age
      group.

PMID- 25993755
TI  - Risk factors of lymph node metastasis in patients with gastric neuroendocrine
      tumor with normal serum gastrin level.
AB  - BACKGROUND/AIMS: Locoregional gastric carcinoids with normal serum gastrin level
      have been recommended radical resection regardless of tumor size or depth of
      invasion. However, there have been some reports which showed small sporadic
      gastric carcinoids could be treated with local resection. The aim of this study
      was to elucidate risk factors of lymph node metastasis in patients with gastric
      carcinoids with normal serum gastrin level and determine the indications for
      limited resection such as endoscopic treatment. METHODOLOGY: We performed
      clinicopathologic reviews of thirty gastric carcinoids with normal serum gastrin
      level from January 1996 to December 2010. RESULTS: One case show distant
      metastasis and two cases showed lymph node metastasis at the time of diagnosis.
      For twenty seven cases which showed no regional lymph node or distant metastasis
      initially no additional lymph node or distant metastasis were diagnosed
      throughout the follow up period. Large tumor size (>10 mm), proper muscle
      infiltration, WHO classification grade 2 and lymphovascular invasion was noted
      risk factor of lymph node metastasis by univariate logistic regression analysis.
      CONCLUSIONS: Small (<=10 mm) gastric carcinoids with normal serum gastrin level
      confined to submucosa can be treated with endoscopic or local resection unless
      lymphovascular invasion.

PMID- 25993759
TI  - Millionaires at your doorstep.

PMID- 25993756
TI  - Interferon alpha2b increases MMP-13 and IL-10 expression in Kupffer cells through
      MAPK signaling pathways.
AB  - BACKGROUND/AIMS: Kupffer cells play critical roles in both progression and
      resolution of liver fibrosis. Interferon alpha2b is an important immunoregulator
      which has anti-fibrotic effect in addition to its antiviral effect. It remained
      unclear whether the anti-fibrotic effect of interferon alpha2b is mediated by
      regulating functions of Kupffer cells. METHODOLOGY: Primary isolated Kupffer
      cells were cultured with interferon alpha2b and the expression of matrix
      metalloproteinase-13, interleukin-10, transforming growth factor -beta1 and tumor
      necrosis factor-alpha were measured. To investigate the role of mitogen-activated
      protein kinase pathways in regulating cytokines production by interferon alpha2b
      stimulated Kupffer cells, inhibitors were given before cells were treated with
      interferon a2b. RESULTS: Cell purity was more than 98%. Stimulating Kupffer cells
      with interferon alpha2b led to a dramatic increase in matrix metalloproteinase-13
      and interleukin-10 expression. In contrast, the values of tumor necrosis factor
      alpha and transforming growth factor -beta1 remained unchanged throughout the 24
      hour observation period. Inhibited ERK1/2 pathway prevented interferon alpha2b
      triggered matrix metalloproteinase-13 production, while inhibited p38MAPK, ERK1/2
      or JNK signaling pathways all blocked interleukin-10 expression. CONCLUSIONS:
      Interferon alpha2b may exert anti-fibrotic effect by elevating the level of
      matrix metalloproteinase-13 and interleukin-10 in Kupffer cells, in a mitogen
      activated protein kinase signaling pathways-dependent manner.

PMID- 25993760
TI  - Making the most of grateful patient programs.

PMID- 25993761
TI  - Engaging physicians in transformational philanthropy.

PMID- 25993762
TI  - Adding "E" to philanthropy.

PMID- 25993763
TI  - AMS job one.

PMID- 25993764
TI  - AMS' Fall HOD meeting emphasizes legislative session.

PMID- 25993765
TI  - Health literacy: increasing pharmacological compliance.

PMID- 25993766
TI  - Assessment of hydrocodone prescribing within a family medicine residency program.
AB  - BACKGROUND AND OBJECTIVES: Hydrocodone is one of the most frequently prescribed
      medications in the United States. Chronic users of hydrocodone are high-risk
      patients who consume valuable time and resources within a Family Medicine
      Residency Program. A narcotic agreement is a tool to help providers define
      patient expectations regarding chronic medication use. Objectives of this project
      were to classify hydrocodone utilizers by frequency of use, determine use of
      narcotic agreements in chronic users, and evaluate patients' ad- herence to
      agreement parameters. METHODS: A report was created for all hydrocodone
      prescriptions generated between January and June 2013. Patients were classified
      as acute, episodic or chronic users. Clinic records were reviewed to determine if
      chronic users had an existing narcotic agreement with the Family Medical Clinic
      (FMC). Adherence to agreement criteria was assessed by reviewing the Arkansas
      Prescription Monitoring Program. RESULTS: A total of 371 patients received
      hydrocodone prescriptions; forty-eight percent (N = 177) were chronic users.
      Chronic users accounted for 85% (N = 44,693) of the 52,478 hydrocodone units
      prescribed. Forty-four percent (N = 78) of chronic users had a narcotic
      agreement; 37% (N = 29) were completely compliant with the terms. CONCLUSIONS:
      The majority of hydrocodone prescribed within our FMC during the study period was
      for chronic users, most of whom did not have narcotic agreements. A minority of
      patients with agreements were adherent to all parameters. Identifying chronic
      utilizers in a timely manner, standardizing implementation of narcotic
      agreements, and integrating prescription database monitoring into routine care
      would permit pro- viders to more appropriately manage these high risk patients.

PMID- 25993767
TI  - Cholesterol and family history: when genetics matters.
AB  - Familial hypercholesterolemia (FH) is an inherited, autosomal codominant disease
      that increases the risk for cardiovascular mortality by 100 fold. Patients
      usually have LDL levels above 300 mg/dl. Although signs such as tendon xanthomas,
      xanthelasmas and corneal arcus may suggest the diagnosis, genetic testing is
      the'most accurate way of diagnosing FH. Genetic testing has been shown to be a
      cost-efficient method to screen individuals and their relatives for FH.
      Establishing an accurate diagnosis is important: high potency statins are first
      choice agents, the treatment goal is at least a 50% reduction in LDL cholesterol,
      and LDL apheresis may be indicated.

PMID- 25993768
TI  - Thrombotic thrombocytopenic purpura.

PMID- 25993769
TI  - [Editorial].

PMID- 25993770
TI  - [Vaginal birth after cesarean. A safe option?].
AB  - OBJECTIVE: To compare the beginning and evolution of labor variables such as
      demographic characteristics, obstetric and perinatal outcomes of patients with
      vaginal birth after cesarean (VBAC). MATERIAL AND METHODS: Observational,
      retrospective and retro elective trial purposes of comparative analysis, were
      divided into groups by the onset of labor; spontaneously versus induction and by
      the labor evolution; spontaneously versus conduction. Being analyzing by
      Student's T and Fisher test. RESULTS: According the ACOG criteria. 136 patients
      with prior cesarean section were eligible to labor. The indications of previous
      cesarean have a trend of a non-recurring etiology, being the elective cesarean
      section the most common. Regarding the onset, 78% was spontaneous and 22% had an
      induction. Comparing the demographic characteristics it stands a greater number
      of deliveries, history of vaginal delivery, a higher Bishop score, fetal weight
      estimated lower and higher intergenesic period. As a perinatal prognosis, the
      study has shown be safe with a positive outcome. Conclusions:Vaginal birth after
      cesarean is safe, that should be offered to all women with a low transverse
      incision, with an intergenesic period greater than 18 months, whit a singleton
      pregnancy, in a cephalic presentation, with an appropriate fetal weight, and
      without obstetric contraindications of vaginal delivery.

PMID- 25993771
TI  - [Surgical-pathologic correlation to assess the margin status in wide local
      excision for early-stages breast cancer].
AB  - OBJETIVE: To know the surgical-pathologic correlation to assess the state of the
      edges in wide local excisions of breast cancer in clinical stages. MATERIAL AND
      METHODS: retrospective and descriptive study, conducted in Breast Tumors Unit
      from Oncology Service of the General Hospital of Mexico, in the period from
      January 2009 to December 2011, with follow-up in December2012. Were included
      patients with breast cancer in early clinical stages, subject wide local
      excisions histopalogic report of a second surgery. RESULTS: From wide local
      excisions, 119 (28.5%) were due to breast cancer and included. Positive margins
      after initial surgery were diagnosed in 63 patients (52.9%). The residual tumor
      found in the second surgery was 39.7%. The variables associated with the presence
      of positive margins and statistically significant (p<= 0.05) were:
      multicentricity, tumor size clinical and pathological, histological subtypes, and
      tumor grade. The age and clinical stage were not statistically significant. The
      variables associated with the presence of residual tumor and are statistical
      relevance (p<= 0.05) were clinical stage, tumor size, clinical and pathological,
      histological variant and histological grade. Age and multicentricity were not
      associated with the presence of residual tumor. CONCLUSION: Although each case
      must be individualized, these results demonstrate the analyzed factors must be
      taken into account during the planning of breast conservative procedures, and
      despite an histopalogical report of margin after an initial surgery, even seconds
      procedures can be performed to conserve the organ.

PMID- 25993772
TI  - [Maternal morbidity and mortality and risk factors related to an obstetric
      emergency].
AB  - BACKGROUND: When studyng the risk factors associated to maternal morbidity and
      mortality due to an obstetric emergency, their causes can be identified
      OBJECTIVE: To identify factors predisposing maternal morbidity and mortality in
      the Regional Hospital of Poza Rica in 2012. MATERIAL AND METHODS: A retrospective
      cross-sectional descriptive survey, was done based on a convenience obtained
      survey in patients. Percentages and contingency tables were used for each
      variable; calculating the prevailing global prevalence and that of exposed and
      unexposed to the risk factor studied. Odds ratio was used to evaluate the above,
      we use the test of Mantel and Heanzel ji; the result was compared to 1.96 with a
      confidence interval of 95%. RESULTS: There were included 364 patients in wich the
      main causes of mortality were bleeding in the first quarter 45% (n=164)
      hypertensive disorders 40% of cases (n=146). Risk factors with a significant
      association (p < 0.05) were for preeclampsia: to be primiparous whit a PR of
      1.56, FEp 19.6% and 35% FEe; maternal age < 20 and > 35 years old RP 1.11; Fee
      Fee 4.3% and 48%; and for abortion parity >=4 with RP 1.42, FEP 7.2% fee 29%.

PMID- 25993773
TI  - [Effect of sexual abstinence on pregnancy rates after an intrauterine
      insemination].
AB  - BACKGROUND: There are many studies showing that more days of sexual abstinence
      increased sperm concentration, however, the direct influence between the days of
      abstinence and pregnancy rates has not been evaluated. The usual recommendation
      is 3-4 days prior to intrauterine insemination; this based on the interval that
      maximizes the number of motile sperm in the ejaculate. There are some reports
      with better success rate when abstinence is less than three days. OBJECTIVE: To
      evaluate the pregnancy rate post-intrauterine insemination according to days of
      sexual abstinence prior to obtaining semen sample. PATIENTS AND METHODS: A
      retrospective, observational and transversal study in patients attending the
      Mexican Center for Fertility (CEPAM) to intrauterine insemination. For analysis
      patients were grouped by age group, success rate and days of sexual abstinence.
      Continuous variables are reported as means and standard deviations; to determine
      statistical significance univariate logistic regression was performed.
      Categorical variables were evaluated in frequencies and percentages. The
      calculations were performed using JMP software program. RESULTS: 3,123 couples
      were included and increased success rate for intrauterine insemination was
      obtained with less than seven days of sexual abstinence. The rate of sperm
      retrieval is inversely proportional to the days of abstinence. CONCLUSION: A
      better pregnancy rate in intrauterine insemination was achieved with less than
      seven days of sexual abstinence and sperm retrieval rate was also recorded with
      fewer days of abstinence.

PMID- 25993774
TI  - [Anterior pelvic exenteration. Report of a case].
AB  - Anterior pelvic exenteration is the last opportunity to control disease in a
      patient with cervical cancer in an advanced stage with a vesico-vaginal fistula,
      or in a patient with persistence of the disease and the need of improving the
      quality of life. In this case we present the cause of a 62 year old patient, with
      IVa stage cervical cancer, with bladder spread and a vesico-vaginal fistula
      treated with an anterior pelvic exenteration with Bricker technique and adjuvant
      treatment with radiotherapy.

PMID- 25993775
TI  - [Postpartum spontaneous pneumomediastinum and subcutaneous emphysema].
AB  - Spontaneous pneumomediastinum is the presence of free air contained within the
      mediastinum, frequently associated with subcutaneous emphysema and of atraumatic
      origin. Frequency during childbirth is 1 in 100,000. We report the case of a 19
      year old woman without respiratory disease history, in her first pregnancy with
      39.5 weeks of gestation patient had, prolonged latent phase and sudden postpartum
      onset of dyspnea, thoracic pain and subcutaneous emphysema. Simple X ray film and
      thoracic tomography revealed the presence of free air in the mediastinum. The
      association of pneumomediastinum during delivery is an uncommon event.

PMID- 25993776
TI  - [Chemical peritonitis after a bladder lesion during a cesarean section. A case
      report and literature review].
AB  - This paper reviews the case of a patient who underwent a cesarean surgery and re
      entered with an oral way intolerance, postprandial emesis, abdominal pain and
      clear-fluid exit from surgical wound. After possible bladder injury and secondary
      chemistry peritonitis, the patient was taken to surgery where the diagnosis was
      confirmed, and the correction of bladder injury as well as peritoneal lavage were
      performed, it antibiotic therapy for three days and the patient had satisfactory
      evolution. Bladder injury is a rare complication of cesarean section with an
      estimated incidence between 0.0016 and 0.94%; but if it is not diagnosed
      intraoperative it can trigger a clinical setting of secondary chemical
      peritonitis, due to secondary irritation of the peritoneum. Chemical peritonitis
      is among the classification of secondary peritonitis. Within the pathophysiology,
      the mechanical, chemical or bacterial stimulus generates an inflammatory
      reaction, with progressive generation of exudate, leukocytes and fibrin deposit,
      which injure mesothelial cells, disrupt the defense and maintenance of peritoneal
      homeostasis, triggering serious complications, which can lead to multiple organ
      failure and death. The chemical peritonitis should be suspected with the clinical
      setting and the risk factors of recent surgical history and timely management
      should be instituted properly with correction of the cause, antimicrobial
      treatment, blood volume therapy and nutritional support, which leads to a
      favorable outcome for the patient and improves survival with fewer complications.

PMID- 25993777
TI  - [Contraception and bioethics: between the conscience objection and the autonomy
      principle].
AB  - In recent years, in all Western societies has changed the paradigm of the
      physician-patient relationship. It has passed from the principle of beneficence
      and abscence of malificence to the patients autonomy, recognizing their
      sovereignty in making clinical decisions that directly affect them. Occasionally,
      this principle can clash with certain bioethical aspects of conscientious
      objection for health professionals and providers, primarily in the areas of
      contraception and abortion. We discussed aspects that support one or another
      attitude emphasizing issues relating to contraception and induced abortion and
      the access and use of contraceptive methods by adolescents recognized as "mature
      minors" to issues of sexuality, particularly in Spain and Mexico.

PMID- 25993778
TI  - [Network formulaology: a new strategy for modern research of traditional Chinese
      medicine formulae].
AB  - This paper briefly analyzed and discussed the current status and major scientific
      challenges of traditional Chinese medicine (TCM) formulaology research. To
      promote formulaology research, a new strategy and corresponding technology,
      network formulaology, were proposed to reveal the complex interaction between
      functional chemome and biological responses network. The research framework and
      directions of network formulaology were also summarized and prospected.

PMID- 25993779
TI  - [Controllability pyramid: an integrated control system of quality for traditional
      Chinese medicines].
AB  - Quality control is one of the key scientific tissues in the modernization of
      traditional Chinese medicines (TCM). In order to overcome the deficiencies of
      assessment indexes, including little systematization and quantification, as well
      as loose association with clinical efficacy and dosage, a new integrated method
      named controllability pyramid ( CP) is first proposed in this paper. In addition,
      some study cases are used to explain how this model is constructed. We hope the
      establishment of CP could promote the clinical-orien- ted integrated innovation
      research of TCM, and provide control strategy and technology examples for
      improving the quality of Chinese medicines and clinical efficacy.

PMID- 25993780
TI  - [Methodology for systematic analysis of in vivo efficacy material base of
      traditional Chinese medicine--Chinmedomics].
AB  - The efficacy material base of traditional Chinese medicines (TCMs) is those
      constituents absorbed in blood and show the efficacy of TCMs after oral
      administration of a TCM formula. In TCM, formula consisted of more than one
      herbal drug is the clinical medication form which corresponding to TCM syndrome.
      The efficacy material base of TCMs had to be found in the condition of
      compatibility and efficacy of TCM formula. Therefore we take the biological
      characters of TCM syndrome as a research starting point, taking formula as
      object, through the integration of serum pharmacochemistry of TCM methods and
      metabolomics technologies, establish a system research methodology of the
      efficacy material basis in vivo--Chinmedomics. The use of metabolomics technology
      is used to fully understand nature biology on syndromes or disease, identify
      biomarkers for disease to bridging disease animal model, establishing the
      biological evaluation system of traditional Chinese medicine. On the basis of the
      validity of the premise, the use of serum pharmacochemistry of TCM to analysis in
      vivo directly substance after oral prescription and dynamic law, combined with
      changes law of the endogenous disease biomarkers (pharmacodynamic markers of
      TCM), Though establishing two variable correlation analysis method between
      Chinese chemical compositions in serum exogenous and endogenous biomarkers, to
      extract TCM compositions highly correlated with the endogenous marker as
      potential basis for traditional Chinese medicines, and to biological validation
      to determine the efficacy material basis of TCM.

PMID- 25993781
TI  - [Research status, development and utilization of traditional Dai medicine in
      China].
AB  - OBJECTIVE: To provide a reference for the development and utilization of Dai
      medicine by investigate the present situation and existing problems of
      traditional Dai medicine. METHOD: Combined with the previous relevant
      investigations and literature in the field, the key and the development direction
      of traditional Dai medicine were analyzed. RESULT: The textual research, history,
      species, distribution, endangered resources, protection status etc. were
      elaborated and the key strategy of further investigation was expounded.
      CONCLUSION: Dai medicine resources should strengthen the basic research, such as
      the protection of traditional knowledge, the textual research, quality standard,
      chemical composition, biological activity, exploration of medicinal resources,
      especially monographic study on protection of major endangered medicinal
      resources should be intensified, which will be rise the level of development and
      utilization of Dai medicine resources.

PMID- 25993782
TI  - [Advance in prevention and treatment of ischemia cardio-cerebrovascular disease
      through increased therapeutic angiogenesis induced by traditional Chinese
      medicine].
AB  - Remaining organic and functional damage of ischemia cardio-cerebrovascular
      disease is always a main trouble puzzling the clinicians. After the discovery of
      endothelial progenitor cells (EPCs), researchers realize that postnatal
      angiogenesis is an important biological process, which play a key role to repair
      the ischemia tissue and improve the function. So a new concept which names
      therapeutic angiogenesis supply a new treament way for the ischemia cardio
      cerebrovascular disease. Traditional Chinese medicine (TCM) has accumulated rich
      experience on treating the ischemia disease, studies found that many Chinese
      medicine prescriptions and effective ingredients can increase the therapeutic
      angiogenesis, howerer the mechanisms were not the same, they mainly manifest in
      regular the secretion of angiogenic factors, increase the proliferation and
      differentiation etc. In this paper, we review recent studies, summary the Chinese
      medicine prescriptions and effective ingredients which can increase the
      therapeutic angiogenesis, and analyze the differernt pathway. We view to provide
      reference for the later researchers.

PMID- 25993783
TI  - [Status of libraries and databases for natural products at abroad].
AB  - For natural products are one of the important sources for drug discovery,
      libraries and databases of natural products are significant for the development
      and research of natural products. At present, most of compound libraries at
      abroad are synthetic or combinatorial synthetic molecules, resulting to access
      natural products difficult; for information of natural products are scattered
      with different standards, it is difficult to construct convenient, comprehensive
      and large-scale databases for natural products. This paper reviewed the status of
      current accessing libraries and databases for natural products at abroad and
      provided some important information for the development of libraries and database
      for natural products.

PMID- 25993784
TI  - [Advances in study of dioscin--a natural product].
AB  - Dioscin, a typical saponin, is widely present in the family of Dioscoreaceae,
      Liliaceae, Caryophyllaceae and Rosaceae, especially in Dioscoreaceae, including
      Discorea nipponica Makino, Dioscorea zingiberensis C. H. Wright and Dioscorea
      panthaica Prain et Burkill. Traditional Chinese medicine reported that dioscin
      plays a role in expectorant, relaxing the muscles and stimulating the blood
      circulation, aiding digestion and diuresis. With the development of science and
      technology in recent years, some new extraction and separation techniques and
      methods have been applied to the study of dioscin, and more and more
      pharmacological effects were found. Modern pharmacology studies have confirmed
      that dioscin had some activities on desensitization, anti-inflammatory, lipid
      lowering, anti-tumor, hepatoprotection and anti-viral. After oral administration,
      dioscin is metabolized to diosgenin, which is the true active ingredient and is
      an important raw material to synthesize steroid hormone drugs. Therefore, the
      studies on dioscin are valueable and promising. In this review, we make a summary
      on the researches of dioscin including the extraction technology, separation and
      prepara- tion, chemical synthesis, drug metabolism, determination and
      pharmacological researches.

PMID- 25993785
TI  - [Cloning and expression analysis of a zinc-regulated transporters (ZRT), iron
      regulated transporter (IRT)-like protein encoding gene in Dendrobium officinale].
AB  - The zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like
      protein (ZIP) plays an important role in the growth and development of plant. In
      this study, a full length cDNA of ZIP encoding gene, designed as DoZIP1 (GenBank
      accession KJ946203), was identified from Dendrobium officinale using RT-PCR and
      RACE. Bioinformatics analysis showed that DoZIP1 consisted of a 1,056 bp open
      reading frame (ORF) encoded a 351-aa protein with a molecular weight of 37.57 kDa
      and an isoelectric point (pI) of 6.09. The deduced DoZIP1 protein contained the
      conserved ZIP domain, and its secondary structure was composed of 50.71% alpha
      helix, 11.11% extended strand, 36.18% random coil, and beta turn 1.99%. DoZIP1
      protein exhibited a signal peptide and eight transmembrane domains, presumably
      locating in cell membrane. The amino acid sequence had high homology with ZIP
      proteins from Arabidopsis, alfalfa and rice. A phylogenetic tree analysis
      demonstrated that DoZIP1 was closely related to AtZIP10 and OsZIP3, and they were
      clustered into one clade. Real time quantitative PCR analysis demonstrated that
      the transcription level of DoZIP1 in D. officinale roots was the highest (4.19
      fold higher than that of stems), followed by that of leaves (1.12 fold).
      Molecular characters of DoZIP1 will be useful for further functional
      determination of the gene involving in the growth and development of D.
      officinale.

PMID- 25993786
TI  - [Effects of low temperature on dormancy breaking and growth after planting in
      bulbs of Tulipa edulis].
AB  - The effect of low temperature storage on dormancy breaking, sprouting and growth
      after planting of Tulipa edulis was studied. The results showed that starch
      content and activity of amylases significantly decreased during 10 weeks of cold
      storage, soluble protein content raised at first then decreased, and the peak
      appeared at the 6th week. However, total soluble sugar content which in- creased
      slowly at first than rose sharply and reducing sugar content increased during the
      storage duration. The bulbs with cold storage treatment rooted in the 6th week,
      which was about 2 weeks earlier than room temperature storage, but there were
      less new roots in the late period of storage. After stored at a low temperature,
      bud lengths were longer than that with room temperature treatment. Cold storage
      treatment could promote earlier emergence, shorten germination time, prolong
      growth period and improve the yield of bulb, but rarely affect the emergence
      rate. It was not beneficial to flowering and fruiting. The results indicated that
      6-8 weeks of cold storage was deemed to be the key period of dormancy breaking
      preliminary.

PMID- 25993787
TI  - [Establishment of adventitious root culture system and scale-up fermentation of
      Tripterygium wilfordii].
AB  - Using MS as basic medium, supplemented with 1.0 mg . L(-1) IBA, the adventitious
      roots of Tripterygium wilfordii were induced, and the good adventitious root
      culture system was established by leaves or callus induced by leaves as explants.
      The adventitious roots were also induced with 2.0-4.0 mg . L(-1) NAA and the good
      adventitious root culture system established by using suspension cells from
      callus as materials to induce adventitious root. The content of triptolide of
      three adventitious roots culture system were exceeded in the natural root bark.
      The content of triptolide of AR3 adventitious roots was the highest about 5.3
      times as that in the natural root bark. By using 5 L stirred fermentor during
      pilot enlarge cultivation, compared with 250 mL flask cultivation, the
      adventitious roots increment and secondary metabolites content per liter medium
      showed no significant difference. The accomplishment of this analysis laid a
      foundation by tissue culture production of the secondary metabolites of T.
      wilfordii.

PMID- 25993788
TI  - [Expression profiles analysis of two member of squaleneepoxidase gene family from
      Eleutherococcus senticosus].
AB  - In order to find the characteristics of two members of gene family of
      squaleneexpoxidase (SE) , a quantitative real time PCR method was developed to
      analyze the expression of Eleutherococcus senticosus SE1 and SE2 gene from
      different growth periods and in different organs. The result indicated that all
      the expression of SE2 more than SE1 in the whole growth period and organs of E.
      senticosus. And in the whole growth period, expression of SE1 showed a low-high
      low characteristic. Both expression of SE2 and growth period showed the same
      trend. The lowest content of the expression was in the roots. SE1 expression have
      been improved more than SE2 when treated with MeJA. The expression of E.
      senticosus SE1 and saponins content had significantly positive correlation (P <
      0.05) and the correlation coefficients was 0. 858, while the correlation was not
      significant for SE2. That indicated that SE1 played a key enzyme gene in the
      biosynthesis of triterpenoidsaponins

PMID- 25993789
TI  - [Community structure and difference of endophtic bacteria in Aquilaria sinensis
      with and without agarwood].
AB  - Aquilaria sinensis can generate agarwood, which is closely related with
      endophyte. Up to now, studies mainly focused on the effects of endophytic fungi
      on agarwood formation, but studies about endophytic bacteria are rarely reported.
      In our research, the T-RFs and Shannon index of endophytic bacteria in samples of
      agarwood increase. The number of distinctive T-RFs fragments of corresponding
      samples in the same group accounted for more than 60% the number of total T-RFs
      fragments. In samples of no-agarwood, the dominant bacterial population are
      Anoxybacillus, Clostridium, Candidatus endobugula, Lysinibacillus. In samples of
      agarwood, the dominant bacterial population are Clostridium, Lysinibacillus,
      Luteimonas, phytoplasma. Besides, there are. specific T-RFs fragment in samples
      of agarwood and no-agarwood respectively. When we perform cluster analysis, we
      found samples of agarwood highly gather together and samples of no-agarwood
      highly gather together. This means community of endophytic bacteria emerge
      significant and regular changes during agarwood formation, which may be result of
      agarwood production, or maybe it is important reason of agarwood production. In
      this paper, we obtain more comprehensive and accurate community of endophytic
      bacteria in Aquilaria sinensis and it's variation during agarwood formation using
      T-RFLP, which is first study of effects of endophytic bacteria on agarwood
      formation, and will help to exploit resource of endophytic bacteria more
      reasonably.

PMID- 25993790
TI  - [Effects of constant low temperature on cold resistance of different strains
      Polygonatum odoratum].
AB  - In this paper, the five strains of Polygonatum odoratum were used as the
      experimental materials to test the supercooling point, freezing point, the degree
      of supercooling, the transition stage time, cooling time and water composition of
      the plant tissue. The cold resistance of P. odoratum was analyzed with the Gray
      Correlation Method. The results showed that the cold resistances of the five
      strains of P. odoratum were different, and the water content of plant tissue had
      some relevance with freezing point and supercooling point, whereas, it could not
      be measured when the moisture content was too low. The order of cold resistance
      of the five strains of P. odoratum was ZJCY, DYYZ, XYYZ, CYYZ and JZ I.

PMID- 25993791
TI  - [Development of Tripterygium glycosides nano-carries based on "nanoemulsion-gels"
      and its pharmacodynamics].
AB  - The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels
      and investigate its pharmacodynamics. Oleic acid was used as oil phase,
      polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to
      screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary
      phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were
      sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the
      model of mouse chronic dermatitis and eczema. The concentrations of IFN-gamma, IL
      4 and IL-8 in mouse blood were determined by ELISA. The results showed that
      Tripterygium glycosides nanoemulsion gels could significantly inhibit the
      swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model
      mouse ears skin. Also it could significantly decrease the expression of IFN-gamma
      and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a
      good therapeutic effect on mouse model of dermatitis and eczema. It was expected
      to provide a new and long-acting exterernal preparation for the treatment of
      dermatitis and eczema.

PMID- 25993792
TI  - [Preparation of hydrophilic matrix sustained release tablets of total lactones
      from Andrographis paniculata and study on its in vitro release mechanism].
AB  - In this study, hydrophilic matrix sustained release tablets of total lactones
      from Andrographis paniculata were prepared and the in vitro release behavior were
      also evaluated. The optimal prescription was achieved by studying the main factor
      of the type and amount of hydroxypropyl methylcellulose (HPMC) using single
      factor test and evaluating through cumulative release of three lactones. No burst
      drug release from the obtained matrix tablets was observed. Drug release
      sustained to 14 h. The release mechanism of three lactones from A. paniculata was
      accessed by zero-order, first-order, Higuchi and Peppas equation. The release
      behavior of total lactones from A. paniculata was better agreed with Higuchi
      model and the drug release from the tablets was controlled by degradation of the
      matrix. The preparation of hydrophilic matrix sustained release tablets of total
      lactones from A. paniculata with good performance of drug release was simple.

PMID- 25993793
TI  - [Changing rules study of effective components of Glycyrrhizae Radix et Rhizoma
      before and after compatibilities in Sini decoction].
AB  - The change of the effective components (liquiritin, glycyrrhizic acid,
      liquiritigenin, isoliquiritigenin) contents of Glycyrrhizae Radix et Rhizoma
      (GRR) before and after compatibilities in Sini decoction was studied in this
      paper. Taking single GRR decoction, GRR-Aconiti Lateralis Radix Praeparata (ALRP)
      decoction, GRR-Zingiberis Rhizoma (ZR) decoction and Sini decoction as test
      samples, the contents changing of the four effective components of GRR were
      measured by HPLC. The results showed that the contents of the four effective
      components of GRR in the single GRR decoction was higher than that in other
      samples, and the sequence was single GRR decoction > GRR-ZR decoction > GRR-ALRP
      decoction > Sini decoction. The contents of liquiritin were 11.18, 9.89, 9.67,
      9.17 mg . g(-1); the contents of glycyrrhizic acid were 20.76, 15.58, 11.30, 8.52
      mg . g(-1); the contents of liquiritigenin were 0.66, 0.57, 0.45, 0.24 mg . g(
      1); the contents of isoliquiritigenin were 0.14, 0.07, 0.03, 0.01 mg . g(-1).
      Therefore, the effective components of GRR decreased obviously after GRR
      compatibility with ZR providing scientific basis for GRR relieving the strong
      nature of ZR. The effective components of GRR decreased sharply after GRR
      compatibility with ALRP providing scientific support for the material foundation
      research of GRR reducing the toxicity of ALRP. The effective components of GRR
      decreased further in Sini decoction indicating that the three medicines in Sini
      decoction were interactional, which reflecting the scientific connotation of the
      mutual-restraint/mutual-detoxication, mutual-promotion/mutual-assistance
      compatibilities in Sini decoction.

PMID- 25993794
TI  - [Discrimination of Coptidis Rhizoma and its processed products by odor
      objectify].
AB  - Different processed products of Coptidis Rhizoma have its unique odor, which is
      an important assessment index for pro- cessed products identification of Coptidis
      Rhizoma. Objectify odor as an entry point in this study, an electronic nose
      technology was used, and a suitable method for Coptidis Rhizoma measurement was
      built firstly. Then different processed products of Coptidis Rhizoma were
      detected by the method built. Finally, different processed products were
      identified by combining with chemometrics based on the objective odor information
      obtained. Electronic nose detection indicated that a significant difference in
      odor between different processed products was performed. Coptidis Rhizoma
      processed or not can be distinguished based on statistical quality control (SQC)
      and soft independent modeling of class analogy (SIMCA). Principle component
      analysis (PCA) model showed that Coptidis Rhizoma and its various processed
      products discriminated obviously. In addition, in order to identify the processed
      products of Coptidis Rhizoma, a correct recognition rate of 100% was acquired by
      discriminant factor analysis (DFA) , and the initial identification rate and
      cross-validation recognition rate of linear discriminant analysis (LDA) is 100%,
      94.4% respectively. In conclusion, differentiationin odor of different processed
      Coptidis Rhizoma was performed by the electronic nose technology used, and
      different products Coptidis Rhizoma were dis- criminated by combining with
      chemometrics. This research can be a reference for objective identification in
      odor of traditional Chinese medicine, and is good for the inheritance and
      development of traditional experience in odor identification.

PMID- 25993795
TI  - [Aporphine alkaloids from Litsea greenmaniana].
AB  - A new aporphine alkaloid (1), together with five known analogues (2-6), has been
      isolated from the branch of Litsea greenmaniana by using various chromatographic
      techniques. Their structures were identified by spectroscopic data analysis ( MS,
      IR, 1D and 2D NMR) as 2,9-dihydroxy-1,10-dimethoxy-4,5-dihydro-7-oxoaporphine
      (1), laurotetanine (2), N-methyllaurotetanine (3), isodomesticine (4),
      isocorydine (5), and norisocorydine (6). Compound 1 was a new compound, and
      compounds 2-6 were obtained from this plant for the first time.

PMID- 25993796
TI  - [Diterpenoids from Scutellaria strigillosa].
AB  - By means of preparative HPTLC and column chromatography over silica gel and
      Sephadex LH-20, nine diterpenoids were isolated and purified from the whole
      plants of Scutellaria strigillosa. Based on the physico-chemical properties and
      spectral data, their structures were elucidated as: 6-O-acetyl-7-O
      nicotinoylscutebarbatine G(1), 6-O-nicotinoyl-7-O-acetylscutebarbatine G(2), 6,7
      di-O-nicotinoylscutebarbatine G(3), scutebarbatine K(4), scutebarbatine B(5), 6-O
      acetylscutehenanine A(6), 6-O-nicotinoylbarba- tin A(7), 6,7-di-O
      acetoxylbarbatin A(8), scutebarbatine F(9). Compound 1 is a new diterpenoid, and
      compounds 2-9 were isolated from Scutellaria strigillosa for the first time.

PMID- 25993797
TI  - [Flavonol glycosides from Lysimachia clethroides].
AB  - Eleven flavonol glycosides were isolated from the ethanol extract of Lysimachia
      clethroides by a combination of various chromatographic techniques including
      column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC.
      Their structures were identified as astragalin (1), isoquercitrin (2),
      isorhamnetin-3-O-beta-D-glucopyranoside (3), quercetin-3-O-beta-D-6"
      acetylglucopyranoside (4), quercetin-7-O-beta-D-glucopyranoside (5), prunin (6),
      2-hydroxynaringin-5-O-beta-D-glucopyranoside (7), kaempferol-3-O-rutinonoside
      (8), kaempferol-3-O-robinobioside (9), rutin (10) and kaempferol-3,7-di-O-beta-D
      glucopyranoside (11). Among them, compounds 4, 7 and 11 were obtained from the
      Lysimachia genus for the first time, while compounds 3, 5 and 9 were firstly
      reported from this plant. In the preliminary assays, compounds 2, 6 and 8
      possessed significant inhibition against aldose reduc- tase, with IC50 values of
      2.69, 1.00, 1.80 MUmol . L(-1), respectively; none of compounds 1-11 exhibited
      obvious cytotoxic activity (IC50 > 10 MUmol . L(-1)).

PMID- 25993798
TI  - [Simultaneous determination of flavones and saponins of Rhizoma Anemarrhenae by
      HPLC-DAD-ELSD].
AB  - This study is to establish an HPLC-DAD-ELSD method for simultaneous determination
      of 5 flavones and saponins in Rhizoma Anemarrhenae including neo-mangiferin,
      mangiferin, timosaponin B II, timosaponin B III and timosaponin A III. Samples
      were analyzed on a Merck Purospher STAR column(4.6 mm x 250 mm, 5 MUm). The
      mobile phase consisted of acetonitrile( A) and 0. 1% formic acid (B) with
      gradient elution at a flow rate of 1.0 mL . min(-1). The column temperature was
      set at 40  degrees C. The DAD detector wavelength was set at 254 nm. The ELSD
      conditions were as follows: the nebulizing gas flow rate was 2.0 L . min(-1) and
      temperature of drift tube was 105  degrees C. The volume was 10 MUL. The five
      compounds were well separated with good linear correlations. The mean recoveries
      were between 102.0%-104.0%. This method was quick and reliable which provides a
      foundation for quality control of R. Anemarrhenae.

PMID- 25993799
TI  - [Biological mechanisms of human-derived leukemia stem cells senescence regulated
      by Angelica sinensis polysaccharide].
AB  - OBJECTIVE: To explore the biological mechanisms underlying Angelica sindsis
      polysaccharide (ASP) -induced aging of human-derived leukemia stem cells (LSCs)
      in vitro. METHOD: Acute myelogenous leukemia stem cells were isolated by magnetic
      activated cell sorting (MACS). The ability of LSC proliferation treated by
      various concentration of ASP(20-80 mg . L(-1)) in vitro for 48 hours were tested
      using cell counting Kit-8 ( CCK8) , colony forming were evaluated by
      methylcellulose CFU assay. The ultra structure changes of AML CD34+ CD38- cells
      were analyzed by transmission electron microscopy. The aging cells were detected
      with senescence-beta-galactosidase Kit staining. Expression of aging-related p53,
      p21, p16, Rb mRNA and P16, Rb, CDK4 and Cyclin E protein were detected by
      quantitative reverse transcription polymerase chain reaction( qRT-PCR) and
      Western blotting, respectively. RESULT: The purity of the CD34 + CD38 - cells is
      (91.15 +/- 2.41)% after sorted and showed good morphology. The proliferation of
      LSC was exhibited significantly concentration-dependent inhibited after exposure
      to various concentration of ASP. Treated by 40 mg . L(-1) ASP for 48 hours, the
      percentage of positive cells stained by SA-beta-Gal was dramatically increased (P
      < 0.01) and the colony-formed ability has been weakened (P < 0.01). The
      observation of ultrastructure showed that cell heterochromatin condensation and
      fragmentation, mitochondrial swelling, lysosomes increased in number. Aging
      related p53, p21, p16, Rb and P16, Rb were up-regulated, protein regulatory cell
      cycle CDK4 and Cyclin E were down-regulated. ASP may induce the senescence of
      LSCs effectively in vitro, P16-Rb cell signaling pathway play a significant role
      in this process. CONCLUSION: ASP can induce human leukemia stem cell senescence
      in vitro, the mechanism involved may be related to ASP regulation P16-Rb
      signaling pathways.

PMID- 25993800
TI  - [Protective effect against myocardial ischemia reperfusion injuries induced by
      hyperoside preconditioning and its relationship with PI3K/Akt signaling pathway
      in rats].
AB  - To investigate the protective effect of preconditioning with hyperoside ( Hyp)
      against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of
      PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior
      descending coronary artery for 30 min followed by reperfusion for 120 min in
      rats. Male SD rats were randomly divided into five groups: sham group,model group
      (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt
      signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the
      end of reperfusion, hemodynamic parameters were recorded as left ventricular
      systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and
      maximal rate of increase and decrease of left ventricular pressure (+/-
      dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial
      enzymes indicators and inflammatory factors were also analyzed. The expressions
      of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method.
      The results showed that Hyp preconditioning remarkably improved cardiac
      constriction and relaxation function, reduced myocardial infarct size and
      enhanced the activities of oxidative stress markers about correlated to MIRI,
      such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase
      (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with
      MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine
      kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors,
      for instance tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)
      were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as
      evidenced by decreasing the level of Bax expression, increasing the levels of
      phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by
      LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that
      the cardioprotection of Hyp preconditioning against MIRI may be related to
      activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2
      protein and down-regulating the expression of Bax protein.

PMID- 25993801
TI  - [Astragaloside IV regulates STAT1/IkappaB/NF-kappaB signaling pathway to inhibit
      activation of BV-2 cells].
AB  - OBJECTIVE: The study was aimed to investigate the inhibitory effect and mechanism
      of astragaloside IV (ASI) on the activation of microglial cells. METHOD: After
      pre-incubated with ASI for 2 h, microglial cells BV-2 were stimulated with
      interferon-gamma (IFN-gamma) for 1. 5 h and 24 h, respectively. Secretion of
      nitric oxide (NO) in the medium was measured by Griess method. Production of
      tumor necrosis factor alpha (TNF-alpha) was detected by ELISA approach. Cellular
      gene expressions of CD11b, TNF-alpha, interleukin 1beta (IL-1beta) and induced
      nitric oxide synthase (iNOS) were examined by quantitative-PCR analysis. Total
      and phosphorylation of STAT1, IkappaB and NF-kappaB was analyzed by Western blot
      method. RESULT: ASI could significantly inhibit the increased secretion of TNF
      alpha and NO from BV-2 cells upon IFN-gamma stimulation (P < 0.001). Further
      study showed that ASI significantly down-regulated gene expression of IL-1beta
      and TNF-alpha (P < 0.01, P < 0.05) and exhibited a trend to reduce that of iNOS.
      IFN-gamma and ASI have no obvious effect on gene expression of CD11b. Moreover,
      ASI inhibited the phosphorylation of STAT1, IkappaB and NF-kappaB elicited by IFN
      gamma stimulation. CONCLUSION: ASI could restrain microglial activation through
      interfering STAT1/IkappaB/NF-kappaB signaling pathway, reducing gene expres- sion
      of IL-1beta and TNF-alpha, and thus inhibiting the production of proinflammatory
      mediators such as NO and TNF-alpha.

PMID- 25993802
TI  - [Flavonoids of Echinps latifolius suppress Wnt signaling in adjuvant arthritis
      rats].
AB  - The role of flavonoids of Echinps latifolius (FELT) in Wnt signaling was
      investigated in adjuvant arthritis (AA) rats. The therapeutic effects of FELT on
      AA rats were detected by rat arthritis score and MTT. The effect of FELT gavage
      treatment on the Wnt signaling key gene beta-catenin, C-myc and cyclin D1 in
      synovium from AA rats was detected by Real-time qPCR, and the effects of FELT
      gavage treatment on the upstream negative regulation gene SFRP 1,2,4,5 in
      synovium from AA rats were detected by Real-time qPCR. The results showed that
      FELT gavage treatment significantly inhibited arthritis score and MTT values in
      AA rats, significantly inhibited the expression of the Wnt signaling gene beta
      catenin, C-myc and cyclin D1, significantly up-regulated the expression of the up
      stream negative regulation gene SFRP 1,2,4. FELT has a better therapeutic effect
      for AA rats.

PMID- 25993803
TI  - [Study on intestinal absorption features of oligosaccharides in Morinda
      officinalis How. with sigle-pass perfusion].
AB  - To study the in situ intestinal absorption of five oligosaccharides contained in
      Morinda officinalis How. (sucrose, kestose, nystose, 1F-Fructofuranosyinystose
      and Bajijiasu). The absorption of the five oligosaccharides in small intestine
      (duodenum, jejunum and ileum) and colon of rats and their contents were
      investigated by using in situ single-pass perfusion model and HPLC-ELSD. The
      effects of drug concentration, pH in perfusate and P-glycoprotein inhibitor on
      the intestinal absorption were investigated to define the intestinal absorption
      mechanism of the five oligosaccharides in rats. According to the results, all of
      the five oligosaccharides were absorbed in the whole intestine, and their
      absorption rates were affected by the pH of the perfusion solution, drug
      concentration and intestinal segments. Verapamil Hydrochloride could
      significantly increase the absorptive amount of sucrose and Bajijiasu, suggesting
      sucrose and Bajijiasu are P-gp's substrate. The five oligosaccharides are
      absorbed mainly through passive diffusion in the intestinal segments, without
      saturated absorption. They are absorbed well in all intestines and mainly in
      duodenum and jejunum.

PMID- 25993804
TI  - [Meta-analysis on effect of compound Danshen injection in treating neonatal
      hypoxic-ischemic encephalopathy].
AB  - To systematically evaluate the clinical efficacy and safety of compound Danshen
      injection in treating hypoxic-ischemic encephalopathy (HIE) of newborns. Computer
      retrievals were made in PubMed, Embase, Cochrane Library, CBM, CNKI, VIP and
      China info (before May 2014) and relevant literature references, and manual
      retrievals were made for journals and conference papers, in order to collect
      randomized or semi-randomized controlled trials concerning compound Danshen
      injection in the treatment of neonatal HIE. The quality of included references
      was evaluated according to literatures recommended by Cochrane Handbook. RevMan
      5. 3 software was applied in the statistical treatment. Finally, a total of 13
      randomized controlled trials were included, covering 1,211 patients (including
      639 patients in the compound Danshen injection-treated group and 572 patients in
      the control group). Meta-analysis results showed that the routine treatment
      combined with compound Danshen injection can improve the treatment efficiency of
      neonatal HIE [RR = 1.28; 95% CI (1.21-1.36)], reduce the mortality rate [RR =
      0.42; 95% CI (0.23-0.75)] and the incidence of long-term neurological sequelae
      [RR = 0.48; 95% CI (0.35-0.65)], with statistical differences. No fatal side
      effect was observed in all of included trials. So far, limited evidences in this
      study proved that the application of compound Danshen injection in the treatment
      of neonatal HIE can enhance the clinical efficiency. However, because of the low
      quality of the included trials, more well-designed and large-scale multi-center
      randomized controlled trials shall be made in the future.

PMID- 25993805
TI  - [Controlled clinical study on compound Decumbent Corydalis Rhizome and diclofenac
      in treatment of knee osteoarthritis].
AB  - To evaluate the efficacy and safety of compound Decumbent Corydalis Rhizome (DCR)
      in treating patients with knee osteoarthritis (OA). Totally 79 patients with knee
      osteoarthritis were selected from out-patient and inpatient departments of West
      China Hospital and randomly divided into the test group and the control group.
      The test group (n = 41) was given Compound DCR with the dosage of 1.8 g . d(-1),
      while the control group (n = 38) was administered with diclofenac sodium with the
      dosage of 75 mg . d(-1). After 12 weeks of treatment, the total efficacy rates
      based on patients/physicians evaluation for experimental and control groups were
      68.29%, 63.41% and 71.05%, 63.16%, respectively, without significant difference
      between the two groups. Both of the two groups showed significant improvements in
      the main efficacy indexes (pain on walking 20 m) and minor indexes (tenderness on
      palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short
      Form Health Survey (SF-36 ), but without significant difference in efficacy
      between them. The incidence of related adverse events was 24.39% in the test
      group and 47.37% in the control group, respectively, with significant differences
      between the two groups (P < 0.05). In the controlled study, compound DCR is as
      efficient as diclofenac sodium but more tolerable, with a good clinical
      application prospect.

PMID- 25993806
TI  - [Summary of Hui prescriptions for treating cough].
AB  - By using the method of philology, 65 Hui prescriptions for treating cough were
      been collected to compare Arabic and Chinese names of pennisetum, anemarrhenae,
      honey, pease, white mustard, perilla and towel gourd stem. The Countif function
      in Microsoft Excel 2007 was used to count frequency of drugs in the prescriptions
      and summarize eight common Hui medicine for treating cough, namely sugar, honey,
      almond, fritillaria, liquorice, orange peel, white mulberry root-bark and lily.
      According to the commonly used drugs, philological studies and theories of Hui
      medicines, pathology and therapy of Hui medicines for treating cough were
      preliminarily inferred. In this study, 35 practical prescriptions and 30 simple
      and convenient Halal dietary prescriptions were summarized from collected
      prescriptions according to relevant literatures. On the basis of the long-lasting
      unique dietary therapy culture developed for Hui people, the simple and practical
      dietary prescriptions were defined according indications, therapy, prescription
      name and composition, and eight types of drug-admixed foods were summarized to
      relieve pains and improve health awareness and quality of life. Meanwhile, this
      study could also enrich and perfect the prescriptions, provide new ideas for
      improving health of patients, and lay a certain realistic foundation for further
      study of Hui medicines.

PMID- 25993807
TI  - [Study on methodology for evaluating clinical efficacy of traditional Tibetan
      medicine].
AB  - The evaluation on clinical efficacy of traditional Tibetan medicine (TTM) is an
      important scientific subject during the development of TTM. Firstly, the authors
      introduced the current situations and problems in evaluation on clinical efficacy
      of traditional Tibetan medicine both at home and abroad in this study. Secondly,
      they compared the similarities and differences between TTM and traditional
      Chinese medicine (TCM) in evaluation on clinical efficacy, define their
      differences in details but not in nature, and proposed that TTM could selectively
      learn TCM's experiences in clinical research and build a specific methodology
      system for evaluation on clinical efficacy according to its own characteristics.
      Thirdly, they discussed the methodological challenges in evaluation on clinical
      efficacy of TTM, including the pending clinical research guidelines and disease
      diagnosis standards according to its own characteristics. Finally, they propound
      some suggestions for promoting the evaluation on clinical efficacy of TTM,
      including the comprehensive application of multiple research methods, overall
      research-based evaluation on efficacy of TTM complex intervention and selection
      of accepted and objective outcome indexes for efficacy evaluation.

PMID- 25993808
TI  - [An effective method for improving the imaging spatial resolution of terahertz
      time domain spectroscopy system].
AB  - Terahertz radiation is an electromagnetic radiation in the range between
      millimeter waves and far infrared. Due to its low energy and non-ionizing
      characters, THz pulse imaging emerges as a novel tool in many fields, such as
      material, chemical, biological medicine, and food safety. Limited spatial
      resolution is a significant restricting factor of terahertz imaging technology.
      Near field imaging method was proposed to improve the spatial resolution of
      terahertz system. Submillimeter scale's spauial resolution can be achieved if the
      income source size is smaller than the wawelength of the incoming source and the
      source is very close to the sample. But many changes were needed to the
      traditional terahertz time domain spectroscopy system, and it's very complex to
      analyze sample's physical parameters through the terahertz signal. A method of
      inserting a pinhole upstream to the sample was first proposed in this article to
      improve the spatial resolution of traditional terahertz time domain spectroscopy
      system. The measured spatial resolution of terahertz time domain spectroscopy
      system by knife edge method can achieve spatial resolution curves. The moving
      stage distance between 10 % and 90 Yo of the maximum signals respectively was
      defined as the, spatial resolution of the system. Imaging spatial resolution of
      traditional terahertz time domain spectroscopy system was improved dramatically
      after inserted a pinhole with diameter 0. 5 mm, 2 mm upstream to the sample.
      Experimental results show that the spatial resolution has been improved from 1.
      276 mm to 0. 774 mm, with the increment about 39 %. Though this simple method,
      the spatial resolution of traditional terahertz time domain spectroscopy system
      was increased from millimeter scale to submillimeter scale. A pinhole with
      diameter 1 mm on a polyethylene plate was taken as sample, to terahertz imaging
      study. The traditional terahertz time domain spectroscopy system and pinhole
      inserted terahertz time domain spectroscopy system were applied in the imaging
      experiment respectively. The relative THz-power loss imaging of samples were use
      in this article. This method generally delivers the best signal to noise ratio in
      loss images, dispersion effects are cancelled. Terahertz imaging results show
      that the sample's boundary was more distinct after inserting the pinhole in front
      of, sample. The results also conform that inserting pinhole in front of sample
      can improve the imaging spatial resolution effectively. The theoretical analyses
      of the method which improve the spatial resolution by inserting a pinhole in
      front of sample were given in this article. The analyses also indicate that the
      smaller the pinhole size, the longer spatial coherence length of the system, the
      better spatial resolution of the system. At the same time the terahertz signal
      will be reduced accordingly. All the experimental results and theoretical
      analyses indicate that the method of inserting a pinhole in front of sample can
      improve the spatial resolution of traditional terahertz time domain spectroscopy
      system effectively, and it will further expand the application of terahertz
      imaging technology.

PMID- 25993809
TI  - [Arc spectrum diagnostic and heat coupling mechanism analysis of double wire
      pulsed MIG welding].
AB  - A double wire pulsed MIG welding test system was built in the present paper, in
      order to analyze the heat-coupling mechanism of double wire pulsed MIG welding,
      and study are temperature field. Spectroscopic technique was used in diagnostic
      analysis of the are, plasma radiation was collected by using hollow probe method
      to obtain the arc plasma optical signal The electron temperature of double wire
      pulsed MIG welding arc plasma was calculated by using Boltzmann diagram method,
      the electron temperature distribution was obtained, a comprehensive analysis of
      the arc was conducted combined with the high speed camera technology and
      acquisition means of electricity signal. The innovation of this paper is the
      combination of high-speed camera image information of are and optical signal of
      arc plasma to analyze the coupling mechanism for dual arc, and a more intuitive
      analysis for are temperature field was conducted. The test results showed that a
      push-pull output was achieved and droplet transfer mode was a drop in a pulse in
      the welding process; Two arcs attracted each other under the action of a magnetic
      field, and shifted to the center of the arc in welding process, so a new heat
      center was formed at the geometric center of the double arc, and flowing up
      phenomenon occurred on the arc; Dual arc electronic temperature showed an
      inverted V-shaped distribution overall, and at the geometric center of the double
      arc, the arc electron temperature at 3 mm off the workpiece surface was the
      highest, which was 16,887.66 K, about 4,900 K higher than the lowest temperature
      11,963.63 K.

PMID- 25993810
TI  - [Application of optimized parameters SVM based on photoacoustic spectroscopy
      method in fault diagnosis of power transformer].
AB  - In order to solve the problems such as complex operation, consumption for the
      carrier gas and long test period in traditional power transformer fault diagnosis
      approach based on dissolved gas analysis (DGA), this paper proposes a new method
      which is detecting 5 types of characteristic gas content in transformer oil such
      as CH4, C2H2, C2H4, C2H6 and H2 based on photoacoustic Spectroscopy and
      C2H2/C2H4, CH4/H2, C2H4/C2H6 three-ratios data are calculated. The support vector
      machine model was constructed using cross validation method under five support
      vector machine functions and four kernel functions, heuristic algorithms were
      used in parameter optimization for penalty factor c and g, which to establish the
      best SVM model for the highest fault diagnosis accuracy and the fast computing
      speed. Particles swarm optimization and genetic algorithm two types of heuristic
      algorithms were comparative studied in this paper for accuracy and speed in
      optimization. The simulation result shows that SVM model composed of C-SVC, RBF
      kernel functions and genetic algorithm obtain 97. 5% accuracy in test sample set
      and 98. 333 3% accuracy in train sample set, and genetic algorithm was about two
      times faster than particles swarm optimization in computing speed. The methods
      described in this paper has many advantages such as simple operation, non-contact
      measurement, no consumption for the carrier gas, long test period, high stability
      and sensitivity, the result shows that the methods described in this paper can
      instead of the traditional transformer fault diagnosis by gas chromatography and
      meets the actual project needs in transformer fault diagnosis.

PMID- 25993811
TI  - [Phase transition behavior and thermodynamic analysis of hydrotalcite flame
      retardant].
AB  - The hydrotalcite with the properties of flame-retardant, eliminating smoke,
      filling and thermostability is a new kind of inorganic flame retardant. In the
      work, the MgAl hydrotalcite as flame retardant with Mg/Al molar ratio of 4 (MgAl
      LDH) was prepared by using urea as the precipitating agent. The thermolysis
      behavior of the MgAl-LDH flame retardant was investigated by X-ray diffraction
      (XRD), fourier transform infrared spectroscopy (FT-IR) and thermogravimetry
      differential scanning calorimetry (TG-DSC) as well as self deconvolution and
      curve-fitting analyses. Thermal phase transition of the MgAl-LDH was clarified,
      especially the characteristics of the hydroxyl groups (-OH) in the brucite-like
      layers and the changes in coordinate of the carbonate (CO3(2-)) from the
      interlayers. Based on thermodynamic data, thermal decomposition process was
      discussed. By.XRD analysis; it was found that the phase change took place when
      the decomposition temperature increased. The MgAl-LDH was decarbonated basically
      to MgAl mixed metal oxides (Mg-Al-O) at 500  degrees C, and impurity MgAl204
      phase formed at 600  degrees C. According to the analyses of FT-IR, TG-DSC and
      curve-fitting technique, the hydroxyl groups (-OH) in the brucite-like layers
      possessed three the ligands such as [Al-OH-Al], [Al-OH-Mg] and [Mg-OH-Mg] modes.
      Dehydroxylation of the brucite-like layers based on the binding forces, where the
      [Mg-OH-Mg] among the three modes was the most difficult to be re- moved during
      the pyrolysis process. In the same way, the CO3(2-) ligands also possessed three
      modes such as H2O-bridged CO3(2-), monodentate and bidentate coordination modes.
      Based on the thermodynamic analysis, the thermodynamic properties of the
      hydrotalcite as flame retardant were evaluated, and the expressions of the Gibbs
      free energy, (DeltarGthetaT), as a function of temperature, were derived for the
      Mg8Al2 (OH)20CO3 crystal. Thermodynamic analysis showed that the removal of -OH
      from the brucite-like layers was spontaneous process, when the Gibbs free energy
      (DeltarGthetaT) was under zero at the temperature (T) above 228. 65  degrees C.
      The result and datum were close to the experimental result from the TG-DSC
      analyses, indicating that the relationship between the Gibbs free energy
      (DeltarGthetaT) and temperature (T) from thermodynamic analysis was reliable.

PMID- 25993812
TI  - [Effect of annealing pressure on P3HT : PCBM nanoscale morphology and
      photovoltaic properties].
AB  - The considerable performance enhancement of P3HT-based solar cell after thermal
      annealing can be attributed to the thermodynamically driven partial
      crystallization and phase segregation of each component. In the present work,
      thermal annealing was executed by delivering P3HT : PCBM blend films onto the
      preheated susceptor in a PECVD chamber filled with high purity nitrogen gas. The
      pressure of inner chamber could be set steadily and precisely in the range of 1
      to 1 850 mTorr at 150  degrees C. It was found that the phase segregation scale
      of two components was tuned to a certain extent by varying the annealing
      pressure, whereas the polymer crystallinity was slightly affected. According to
      the pressure settings, polymer solar cells (PSCs) were fabricated in the
      following structure: ITO/PEDOT : PSS/P3HT : PCBM/Al. All of the device parameters
      exhibited the similar trend--an initial increase followed by a decrease, and
      reached a peak at 1500 mTorr with successive increase in annealing setting
      pressure. PSC annealed under 1 500 mTorr shows overall high performances with the
      power conversion efficiency up to 3. 56%. The UV-Vis absorption spectra of
      annealed blend films shows that the vibronic absorption peaks (shoulders) at 510,
      550 and 600 nm became more pronounced under higher setting pressure, which is
      attributed to better crystalline P3HT with increased pi-pi stacking of polymer
      molecules. The AFM results further suggest that high annealing pressure (>1000
      mTorr) promoted the domain formations of P3HT or PCBM; moreover, a moderate phase
      segregation, as a result of an appropriate annealing pressure (1500 mTorr),
      facilitates polymer crystallization which ensures the high charge (hole) mobility
      and consequently increased short-circuit current and fill factor.

PMID- 25993813
TI  - [Preparation and optical properties of tantalum tungsten bronze].
AB  - Tantalum tungsten bronze(TaxWO3)nanowires were successfully synthesized via
      hydrothermal method using TaCl5 and Na2WO4 . 2H20 as raw materials. The
      morphology, crystal structure and optical properties of synthesized products were
      characterized by means of XRD, TEM, SEM, UV-Vis and Raman technologies. The XRD
      results showed that TaxWO3 nanowire exhibited hexagonal structure. By increasing
      the doping content, the cell parameter was kept increasing gradually till Ta/W=
      0. 04, then it remained almost constant. The UV-Vis diffraction spectrum analysis
      showed that the absorption peaks redshifted, the band gap energy decreased with
      increasing the doping content. The Raman peaks moved with a downshift, and the
      peak gradually became broader, which further proved the influence of the tantalum
      doping for tungsten oxide. The reactions of decomposing liquid rhodamine B
      solution showed that the nanosized TaxWO3 had a high photo-catalytic activity.

PMID- 25993814
TI  - K shell and L subshell photoeffect cross-sections of some elements in the atomic
      range 50<=Z<=65 at 59.5 keV.
AB  - In this study, K and L shell photoeffect cross-sections were measured for the
      elements in the range of 50<=Z<=65 at 59. 5 keV. These photoeffect cross-sections
      were measured by using the experimental sigmaKalpha, production cross-section
      values measured in this paper and two different K shell fluorescence yield values
      in the literature. The results were compared with the calculated theoretical
      values. The values were plotted versus atomic number.

PMID- 25993815
TI  - [Measurement of oxygen concentration using multimode diode laser absorption
      spectroscopy].
AB  - Tunable diode laser absorption spectroscopy (TDLAS) is a widely used technique
      for high sensitivity, good selectivity and fast response. It is widely used in
      environment monitoring, industrial process control and biomedical sensing. In
      order to overcome the drawbacks of TDLAS including high cost, poor stability and
      center wavelength shift problem. A multi-mode diode laser system based on
      correlation spectroscopy and wavelength modulation spectroscopy (TMDL-COSPEC-WMS)
      was used to measure O2 concentration near 760nm at the 1%~30% range of near room
      temperature. During the experiment, the light is splitter into two beams,
      respectively through the sample and measuring cell, two receiving optical signal
      collection containing gas concentration information sent back stage treatment,
      invert the oxygen concentration through correlation and ratio between measured
      signal and reference signal, the correlation spectroscopy harmonic detection
      technique is used to improve the stability of the system and the signal to noise
      ratio. The result showed that, there was a good linear relationship between the
      measured oxygen concentration and the actual concentration value. A detection
      limit of 280 pmm. m in the 1 atmospheric which approved of the same sample. A
      continuous measurement for oxygen with the standard deviation of 0. 056% in
      ambient air during approximately 30 minutes confirms the stability and the
      capability of the system. The design of the system includes soft and hardware can
      meet the needs of oxygen online monitoring. The experimental device is simple and
      easy to use, easy to complex environment application.

PMID- 25993816
TI  - [Nerve classification with hyperspectral imaging technology].
AB  - In surgical nerve repair surgery, the identification of nerve fascicles is a key
      to a good repair of their broken end. Some of the existing nerve fascicles
      identification method are not ideal. Hyperspectral imaging (HSI) technology
      provides information of images and spectra of biological tissue at the same time.
      It can supply a qualitative, quantitative and positioning description of the test
      objectives, and identify different biological tissues by biochemical
      characteristic difference, and classify and position these tissues in the image.
      Compared to other medical imaging technology, this techriology has unique
      advantages. In this study, the hyperspectral imaging technology is used in the
      identification and classification of the nerve fascicles by the spectral
      characteristics of different nerve fascicles, and in determining the orientation
      of the nerve fascicles in the image by the image spectral information in order to
      better help surgical personnel to carry out the nerve repair surgery. The
      significance of this paper is: the first to propose a new method of
      identification and location of the nerve fascicles and assist surgical staff to
      improve the efficacy of nerve repair; the second to reserve hyperspectral imaging
      techniques used in qualitative and quantitative and orientation research combined
      with biological organization, and speed up the molecular hyperspectral imaging
      technology to the practical stage.

PMID- 25993817
TI  - [Research on the dynamics of ion debris from Sn plasma by use of dual laser
      pulses].
AB  - Extreme ultraviolet lithography is one of the most promising technologies on the
      next generation of high-capacity integrated circuit manufacturing. However,
      techniques for ion debris mitigation have to be considered in the application of
      extreme ultraviolet source for lithography. In our paper the dynamics of ion
      debris from Sn plasma by using dual ns laser pulses were investigated. The
      results show that debris from plasma greatly depends on the energy of pre-pulse
      and the delay time between the two laser pulses. The energy of Sn ions debris was
      efficiently mitigated from 2. 47 to 0. 40 keV in the case of dual laser pulses,
      up to 6. 1 times lower than that by using single laser pulse. We also found that
      Sn ions debris can be mitigated at all angles by using the dual laser pulses
      method.

PMID- 25993818
TI  - [Investigation on the spectrum of complex self-organized plasma photonic
      crystal].
AB  - A complex plasma photonic crystal (PPC) was obtained by self-organization of
      filaments in air dielectric barrier discharge using two planar water electrodes.
      The PPC structure consists of many square sublattices, and each sublattice is
      composed of large spots, two kinds of small spots and lines, corresponding to
      thick plasma columns, two kinds of thin plasma columns, and plasma slices,
      respectively. By using the optical emission spectrum method, the electron
      densities and molecular vibration temperatures at different positions of the PPC
      were studied. The electron densities were compared by comparing the broadenings
      of Ar I (2P2-->1S5) spectrum line, and the molecular vibration temperatures were
      calculated by the spectrum line of nitrogen band of second positive system (C3Piu
      ->B3Pig) . It was found that the electron densities and molecular vibration
      temperatures at different positions are both different, showing that the plasma
      states at different positions are different. The descending order of the electron
      density is: thin plasma columns around the thick plasma columns, thick plasma
      columns, plasma slices, and thin plasma columns at junction of plasma slices. The
      descending order of the molecular vibration temperature is: thin plasma columns
      at junction of plasma slices, plasma slices, thick plasma columns, and thin
      plasma columns around the thick plasma columns, which is opposite to that of the
      electron density. So, the electron densities and the molecular vibration
      temperatures in different positions of the PPC show the opposite changing trend.
      As the refractive index of plasma is dependent upon the electron density, the
      thick plasma columns, two kinds of thin plasma columns and plasma slices in this
      PPC have different refractive indexes. Together with the surrounding area where
      no discharges occur, in which the refractive index is also different from the
      discharging areas, the complex PPC can be seen as a self-organized periodic
      structure with five different refractive indexes. The PPC has the advantages of
      being obtained easily, having structural diversity, and being analyzed simply,
      which may lead to wide applications in many scientific and technical areas.

PMID- 25993819
TI  - [Plasma temperature of white-eye hexagonal pattern in dielectric barrier
      discharge].
AB  - By using the water-electrode discharge experimental setup, the white-eye
      hexagonal pattern is firstly observed and investigated in the dielectric barrier
      discharge with the mixture of argon and air whose content can be varied whenever
      necessary, and the study shows that the white-eye cell is an interleaving of
      three different hexagonal sub-structures: the spot, the ring, and the halo. The
      white-eye hexagonal pattern has the excellent discharge stability and
      sustainability during the experiment. Pictures recorded by ordinary camera with
      long exposure time in the same argon content condition show that the spot, the
      ring, and the halo of the white-eye hexagonal pattern have different brightness,
      which may prove that their plasma states are different. And, it is worth noting
      that there are obvious differences not only on the brightness but also on the
      color of the white-eye cell in conditions of different argon content, which shows
      that its plasma state also changed with the variation of the argon content. The
      white-eye hexagonal pattern is observed at a lower applied voltage so that the
      temperature of the water electrodes almost keeps unchanged during the whole
      experiment, which is advantageous for the long term stable measurement. The
      plasma state will not be affected by the temperature of the electrodes during the
      continuous discharge. Based on the above phenomena, plasma temperatures of the
      spot, the ring, and the halo in white-eye hexagonal pattern including molecule
      vibrational temperature and variations of electron density at different argon
      content are investigated by means of optical emission spectroscopy (OES). The
      emission spectra of the N2 second positive band(C3Piu-->B3Pig)are measured, and
      the molecule vibrational temperature of the spot, the ring, and the halo of the
      white-eye hexagonal pattern are calculated by the emission intensities.
      Furthermore, emission spectra of Ar I (2P2-->1S5)is collected and the changes of
      its width with different argon content are used to estimate the variations of
      electron density of the spot, the ring, and the halo of the white-eye hexagonal
      pattern. In the same argon content condition, the molecule vibrational
      temperatures of halo, ring, and spot in the white-eye hexagonal pattern are in
      descending order, while the electron densities of halo, ring, and spot are in
      ascending order. With argon content increasing from 70% to 90%, both the molecule
      vibrational temperature and the electron density of the spot increase, while both
      of them of the halo decrease. And the molecule vibrational temperature of the
      ring keeps constant, while its electron density decreases. The experimental
      results indicate that the plasma state of the spot, the halo and the ring in a
      white-eye cell of the white-eye hexagonal pattern is different. These results are
      of great importance to the investigation of the multilayer structure of the
      patterns in dielectric barrier discharge and applications in industry.

PMID- 25993820
TI  - [Discharge characteristic and spectrum measurement of a new type of single
      filament in a dielectric barrier discharge].
AB  - A new type of single filament was observed in a dielectric barrier discharge
      (DBD) system for the first time. It was formed with a larger discharge gap (d=3.
      8 mm) and a smaller discharge area (S= 1 cm x 1 cm) in an air/argon gas mixture.
      Compared with the single filament observed by other experimental groups, the new
      type of single filament is composed of volume discharge (VD) and surface
      discharge (SD). In addition, the single filament has excellent discharge
      stability and sustainability. In order to study more about the discharge
      characteristic of the new type of single filament in a half-cycle of the applied
      voltage and the plasma state in different positions of the discharge column in
      the side view of the new type of single filament, both a high speed framing
      camera (HSFC) and a spectrograph were used in the experiment. The instantaneous
      images of end and side view of the new type of single filament were taken by the
      HSFC with different exposure time, and the discharge characteristic of the new
      type of single filament in a half-cycle of the applied voltage was compared with
      that of glow discharge. The spectral lines of Ar I 763. 26 nm (2P6-->1S5) and Ar
      I 772.13 nm (2P2-->IS3) in different positions of the discharge column of the new
      type of single filament were measured by using optical emission spectra, and
      chosen to estimate the corresponding electron excitation temperature by the
      relative intensity ratio method. It was found that the new type of single
      filament is composed of VD and SD, and SD produces a dendritic discharge around
      VD. The discharge characteristic of the new type of single filament in a half
      cycle of the applied voltage is similar to that of glow discharge, and a funnel
      shaped discharge emerges at the instantaneous cathode. The spectral line
      intensity and the corresponding electron excitation temperature all decrease with
      the distance away from the electrodes, indicating that the plasma state in
      different positions of the discharge column in the side view of the new type of
      single filament is different.

PMID- 25993821
TI  - [Investigation of fibrous cultural materials by infrared spectroscopy].
AB  - Cultural fibrous material includes both important categories, i. e. textile and
      paper, consisting of precious cultural materials in museum, such as costume,
      painting, and manuscript. In recent years more and more connoisseur and
      conservator's concerns are, through nondestructive method, the authenticity and
      the ageing identification of these cultural relics especially made from fragile
      materials. In this research, we used attenuated total reflection infrared
      spectroscopy to identify five traditional textile fibers, alongside cotton,
      linen, wool, mulberry silk and tussah silk, and another five paper fibers
      alongside straw, wheat straw, long qisong, Chinese alpine rush and mulberry bar,
      which are commonly used for making Chinese traditional xuan paper. The research
      result showed that the animal fiber (wool, mulberry silk and tussah silk) and
      plant fiber (cotton and linen) were easier to be distinguished by comparing the
      peaks at 3 280 cm-1 belonging to NH stretching vibration and a serious peaks
      related to amide I to amide III. In the spectrum of wool, the peak at 1 076 cm-1
      was assigned to the S-O stretching vibration absorption of cystine in wool
      structure and can be used to tell wool from silk. The spectrum of mulberry silk
      and tussah silk seems somewhat difficult to be identified, as well as the
      spectrum of cotton and linen. Five rural paper fibers all have obvious
      characteristic peaks at 3 330, 2 900 cm-1 which are related to OH and CH
      stretching vibration. In the fingerprint wavenumber range of 1 600 - 800 cm, the
      similar peaks also appeared at 1 370, 1 320 cm-1 and 1 162, 1 050 cm-1, both
      group peaks respectively are related to CH and CO vibration in the structure of
      cellulose and hemicellulose in paper fibers. Although there is more similarity of
      the infrared spectroscopy of these 5 paper fibers, some tiny difference in
      absorbance also can be found at 3 300 cm-1 and in the fingerprint range at 1 332,
      1 203, and 1 050 cm-1 which are related to C-O-C vibration in cellulose.
      Moreover, in order to explore direct and simple method to identify different
      materials with similar spectrum,. the principal component analysis (PCA) was
      applied to separate cotton and linen, mulberry silk and tussah silk, as well as
      five paper fibers. To eliminate and reduce the spectral scattering caused by
      sample uneven surface roughness, the multiplicative scatter correction (MSC) has
      been applied based on total spectral data. The result showed that the score plot
      using the first two principal components can effectively categorize both group
      textiles of cotton and linen, as well as mulberry silk and tussah silk, and they
      have similar chemical structure. For five paper fibers, the PCA was applied in
      different spectral range (918-550, 1 280-918, 1 700-1 280 and 3 800-2 800 cm-1),
      and the best result appeared in the range from 3 800 to 2 800 cm-1, in which the
      five paper fibers can be well categorized. This research showed that infrared
      spectroscopy combined with principal component analysis has great potential
      advantage on identifying fibrous materials with similar structure.

PMID- 25993822
TI  - [Mineralogical and spectral characteristics of "Gaozhou stone" from Jiangxi
      Province].
AB  - The seal stone is a kind of artwork with historical and cultural characteristics
      of China, which has been playing an important role in Chinese traditional
      culture. "Gaozhou stone", a new kind of the seal stone, has been found in the
      market recently. To investigate the mineralogical and spectral characterastics of
      "Gaozhou stone", samples were studied by using XRF, XRD, FTIR, SEM and DTA.
      Measurements by XRD reveal that kaolin minerals (kaolinite, dickite),
      pyrophyllite and minor sericite and illite occur in the ores. When kaolinite and
      dickite are associated, it is not easy to differentiate them from each other.
      Although some reflections overlap others, kaolin polytypes can be differentiated
      by XRD patterns in the range 18 degrees -40 degrees  (2theta), the reflections at
      0. 395, 0. 379, 0. 343, 0. 326, 0. 294, 0. 280, 0. 232 and 0. 221 nm are
      diagnostic of dickite. The XRD results indicate the presence of transitional
      mineral of kaolinite and dickite in these samples. The main chemical components
      of "Gaozhou stone" are SiO2 and Al2O3 with minor Fe2O3, K2O and Na2O,
      corresponding with that of kaolin minerals. The OH groups in kaolin group
      minerals have attracted considerable attention as a sensitive indicator of
      structural disorder. In principle, dickite has three bands, whereas kaolinite has
      four bands at the OH-stretching region. According to the results of FTIR,
      transitional mineral of kaolinite and dickite in "Gaozhou stone" has 3 absorption
      bands of 3 670, 3 650 and 3 620 cm-1 in high frequency region. The intensity of 3
      670 cm-1 band that belongs to outer layer hydroxyl vibration is approximately
      equal to the intensity of 3 620 cm band ascribing to inner layer OH vibration.
      This value will only have subtle changes due to the different component ratio of
      kaolinite and dickite layers. Micro-morphology viewed by SEM presents irregular
      platy or pseudo-hexagonal platy particles with an average diameter of 0. 5-4 um
      of "Gaozhou stone". Such morphologies are quite similar to other seal stones of
      China that the formation environments of all these stones are of the same kind.
      DTA curves demonstrate that the disparity of dehydroxylation temperature can be
      seen as a differential feature for identifying kaolin group minerals, but that is
      not undoubted. And what's more, the size of the mineral grains seems has a
      greater effect on the disparity of dehydroxylation temperature. This research
      shows that the mineral type of "Gaozhou stone" is similar to "Four Famous stones
      of China", and it could be a viable substitute of other famous seal stones. In
      this point, "Gaozhou stone" has a broad market prospect.

PMID- 25993823
TI  - [Research on the inner wall condition monitoring method of ring forgings based on
      infrared spectra].
AB  - In order to grasp the inner wall condition of ring forgings, an inner wall
      condition monitoring method based on infrared spectra for ring forgings is
      proposed in the present paper. Firstly, using infrared spectroscopy the forgings
      temperature measurement system was built based on the three-level FP-cavity LCTF.
      The two single radiation spectra from the forgings' surface were got using the
      three-level FP-cavity LCTF. And the temperature measuring of the surface forgings
      was achieved according to the infrared double-color temperature measuring
      principle. The measuring accuracy can be greatly improved by this temperature
      measurement method. Secondly, on the basis of the Laplace heat conduction
      differential equation the inner wall condition monitoring model was established
      by the method of separating variables. The inner wall condition monitoring of
      ring forgings was realized via combining the temperature data and the forgings
      own parameter information. Finally, this method is feasible according to the
      simulation experiment. The inner wall condition monitoring method can provide the
      theoretical basis for the normal operating of the ring forgings.

PMID- 25993824
TI  - [Research on specific indicators of waste oil].
AB  - Because both refined "waste oil" and the third category "waste oil" known as
      frying old oil experience a longer history at temperature higher than 200 
      degrees C compared to the vegetable oil. In this study, the relative change rates
      of content of conjugated fatty acid glycerides, content of tans-fatty acid
      glycerides and unsaturation were investigated after being at high temperature for
      several hours by using FTIR-ATR in order to find out specific targets for "waste
      oil". The results show that (1) Starting from 160  degrees C, the contents of
      conjugated fatty acids glycerides and trans-fatty acid glycerids in the vegetable
      oils increase but unsaturation decreases with heating temperature and heating
      time increasing. (2) When heating temperature reaches 200  degrees C or more, the
      heating time up to four hours or longer, the three indicators(conjugated fatty
      glycerids, trans-fatty acid glycerids and unsaturation) of six kinds of vegetable
      oils have substantial changes. (3) The content of linoleic acid in the vegetable
      oil has some contributions to the change amplitude of contents of conjugated
      fatty acid glycerides, and the content of oleic acid in the vegetable oil has
      some contributions to the change amplitude of content of trans-fatty acid
      glycerides. (4) In addition, during the warranty period change amplitudes of
      three indicators are relative small compared with the case of after being at high
      temperature for several hours. Unsaturation decrease and content of conjugated
      fatty acid glycerides increase with storage-time increasing. However, unlike the
      case of after being at high temperature for several hours, the content of trans
      fatty acid glycerids decreases with storage-time increasing. Experimental results
      show that three index value and its variation can be used as specific indicators
      for refined "waste oil" and "waste oil".

PMID- 25993825
TI  - [NIR and XRD analysis of drill-hole samples from Zhamuaobao iron-graphite
      deposit, Inner Mongolia].
AB  - The author analyzed the 4202 drill-hole samples from Zhamuaobao iron-graphite
      deposit by using near infrared spectroscopy(NIR) and X-ray diffraction(XRD)
      measuring and testing techniques, and then compared and summarized the results of
      two kinds of testing technology. The results indicate that some difference of the
      mineral composition exists among different layers, the lithology from upper to
      deeper is the clay gravel layer of tertiary and quaternary, mudstone, mica quartz
      schist, quartz actinolite scarn, skarnization marble, iron ore deposits, graphite
      deposits and mica quartz schist. The petrogenesis in different depth also shows
      difference, which may indicate the geological characteristic to some extent. The
      samples had mainly undergone such processes as oxidization, carbonation,
      chloritization and skarn alteration. The research results can not only improve
      the geological feature of the mining area, but also have great importance in ore
      exploration, mining, mineral processing and so on. What's more, as XRD can
      provide preliminary information about the mineral composition, NIR can make
      further judgement on the existence of the minerals. The research integrated the
      advantages of both NIR and XRD measuring and testing techniques, put forward a
      method with two kinds of modern testing technology combined with each other,
      which may improve the accuracy of the mineral composition identification. In the
      meantime, the NIR will be more wildly used in geography on the basis of mineral
      spectroscopy.

PMID- 25993826
TI  - [Measurement and analysis on complex refraction indices of pear pollen in
      infrared band].
AB  - Pollen is an important part of bioaerosols, and its complex refractive index is a
      crucial parameter for study on optical characteristics and detection,
      identification of bioaerosols. The reflection spectra of pear pollen within the
      2. 5 - 15um waveband were measured by squash method. Based on the measured data,
      the complex refractive index of pear pollen within the wave-band of 2. 5 to 15 um
      was calculated by using Kramers-Kroning (K-K) relation, and calculation deviation
      about incident angle and different reflectivities at high and low
      frequencies.were analyzed. The results indicate that 18 degrees angle of
      incidence and different reflectivities at high and low frequencies have little
      effect on the results, and it is practicable to calculate the complex refractive
      index of pollen based on its reflection spectral data. The data of complex
      refractive index of pollen have some reference value for optical characteristics
      of pollen, detection and identification of bioaerosols.

PMID- 25993827
TI  - [Recognition of water-injected meat based on visible/near-infrared spectrum and
      sparse representation].
AB  - The present paper proposed a new nondestructive method based on visible/near
      infrared spectrum (Vis/NIRS) and sparse representation to rapidly and accurately
      discriminate between raw meat and water-injected meat. Water-injected meat model
      was built by injecting water into non-destructed meat samples comprising pigskin,
      fat layer and muscle layer. Vis/NIRS data were collected from raw meat and six
      scales of water-injected meat with spectrometers. To reduce the redundant
      information in the spectrum and improve the difference between the samples,. some
      preprocessing steps were performed for the spectral data, including light
      modulation and normalization. Effective spectral bands were extracted from the
      preprocessed spectral data. The meat samples were classified as raw meat and
      water-injected meat, and further, water-injected meat with different water
      injection rates. All the training samples were used to compose an atom
      dictionary, and test samples were represented by the sparsest linear combinations
      of these atoms via l1-minimization. Projection errors of test samples with
      respect to each category were calculated. A test sample was classified to the
      category with the minimum projection error, and leave-one-out cross-validation
      was conducted. The recognition performance from sparse representation was
      compared with that from support vector machine (SVM).. Experimental results
      showed that the overall recognition accuracy of sparse representation for raw
      meat and water-injected meat was more than 90%, which was higher than that of
      SVM. For water-injected meat samples with different water injection rates, the
      recognition accuracy presented a positive correlation with the water injection
      rate difference. Spare representation-based classifier eliminates the need for
      the training and feature extraction steps required by conventional pattern
      recognition models, and is suitable for processing data of high dimensionality
      and small sample size. Furthermore, it has a low computational cost. In this
      paper, spare representation is employed for the first time to identify water
      injected meat based on Vis/NIRS, with a promising recognition accuracy. The
      experimental results demonstrate that the proposed method can be effectively used
      for discriminating water-injected meat from raw meat.

PMID- 25993828
TI  - [Research on fast detecting tomato seedlings nitrogen content based on NIR
      characteristic spectrum selection].
AB  - In order to improve the accuracy and robustness of detecting tomato seedlings
      nitrogen content based on near-infrared spectroscopy (NIR), 4 kinds of
      characteristic spectrum selecting methods were studied in the present paper, i.
      e. competitive adaptive reweighted sampling (CARS), Monte Carlo uninformative
      variables elimination (MCUVE), backward interval partial least squares (BiPLS)
      and synergy interval partial least squares (SiPLS). There were totally 60 tomato
      seedlings cultivated at 10 different nitrogen-treatment levels (urea
      concentration from 0 to 120 mg . L-1), with 6 samples at each nitrogen-treatment
      level. They are in different degrees of over nitrogen, moderate nitrogen, lack of
      nitrogen and no nitrogen status. Each sample leaves were collected to scan near
      infrared spectroscopy from 12 500 to 3 600 cm-1. The quantitative models based on
      the above 4 methods were established. According to the experimental result, the
      calibration model based on CARS and MCUVE selecting methods show better
      performance than those based on BiPLS and SiPLS selecting methods, but their
      prediction ability is much lower than that of the latter. Among them, the model
      built by BiPLS has the best prediction performance. The correlation coefficient
      (r), root mean square error of prediction (RMSEP) and ratio of performance to
      standard derivate (RPD) is 0. 952 7, 0. 118 3 and 3. 291, respectively.
      Therefore, NIR technology combined with characteristic spectrum selecting methods
      can improve the model performance. But the characteristic spectrum selecting
      methods are not universal. For the built model based or single wavelength
      variables selection is more sensitive, it is more suitable for the uniform
      object. While the anti-interference ability of the model built based on
      wavelength interval selection is much stronger, it is more suitable for the
      uneven and poor reproducibility object. Therefore, the characteristic spectrum
      selection will only play a better role in building model, combined with the
      consideration of sample state and the model indexes.

PMID- 25993829
TI  - [Study on discrimination of varieties of fire resistive coating for steel
      structure based on near-infrared spectroscopy].
AB  - In order to achieve the rapid identification of fire resistive coating for steel
      structure of different brands in circulating, a new method for the fast
      discrimination of varieties of fire resistive coating for steel structure by
      means of near infrared spectroscopy was proposed. The raster scanning near
      infrared spectroscopy instrument and near infrared diffuse reflectance
      spectroscopy were applied to collect the spectral curve of different brands of
      fire resistive coating for steel structure and the spectral data were
      preprocessed with standard normal variate transformation(standard normal variate
      transformation, SNV) and Norris second derivative. The principal component
      analysis (principal component analysis, PCA)was used to near infrared spectra for
      cluster analysis. The analysis results showed that the cumulate reliabilities of
      PC1 to PC5 were 99. 791%. The 3-dimentional plot was drawn with the scores of
      PC1, PC2 and PC3 X 10, which appeared to provide the best clustering of the
      varieties of fire resistive coating for steel structure. A total of 150 fire
      resistive coating samples were divided into calibration set and validation set
      randomly, the calibration set had 125 samples with 25 samples of each variety,
      and the validation set had 25 samples with 5 samples of each variety. According
      to the principal component scores of unknown samples, Mahalanobis distance values
      between each variety and unknown samples were calculated to realize the
      discrimination of different varieties. The qualitative analysis model for
      external verification of unknown samples is a 10% recognition ration. The results
      demonstrated that this identification method can be used as a rapid, accurate
      method to identify the classification of fire resistive coating for steel
      structure and provide technical reference for market regulation.

PMID- 25993830
TI  - [Study on the genuineness and producing area of Panax notoginseng based on
      infrared spectroscopy combined with discriminant analysis].
AB  - The genuineness and producing area of Panax notoginseng were studied based on
      infrared spectroscopy combined with discriminant analysis. The infrared spectra
      of 136 taproots of P. notoginseng from 13 planting point in 11 counties were
      collected and the second derivate spectra were calculated by Omnic 8. 0 software.
      The infrared spectra and their second derivate spectra in the range 1 800 - 700
      cm-1 were used to build model by stepwise discriminant analysis, which was in
      order to distinguish study on the genuineness of P. notoginseng. The model built
      based on the second derivate spectra showed the better recognition effect for the
      genuineness of P. notoginseng. The correct rate of returned classification
      reached to 100%, and the prediction accuracy was 93. 4%. The stability of model
      was tested by cross validation and the method was performed extrapolation
      validation. The second derivate spectra combined with the same discriminant
      analysis method were used to distinguish the producing area of P. notoginseng.
      The recognition effect of models built based on different range of spectrum and
      different numbers of samples were compared and found that when the model was
      built by collecting 8 samples from each planting point as training sample and the
      spectrum in the range 1 500 - 1 200 cm-1 , the recognition effect was better,
      with the correct rate of returned classification reached to 99. 0%, and the
      prediction accuracy was 76. 5%. The results indicated that infrared spectroscopy
      combined with discriminant analysis showed good recognition effect for the
      genuineness of P. notoginseng. The method might be a hopeful new method for
      identification of genuineness of P. notoginseng in practice. The method could
      recognize the producing area of P. notoginseng to some extent and could be a new
      thought for identification of the producing area of P. natoginseng.

PMID- 25993831
TI  - [Application of near-infrared hyperspectral imaging to predicting water content
      in salmon flesh].
AB  - Near-infrared hyperspectral imaging technique was employed in the present study
      to determine water contents in salmon flesh rapidly and nondestructively.
      Altogether 90 samples from different positions of salmon fish were collected for
      hyperspectral image scanning, and mean spectra were extracted from the region of
      interest (ROI) inside each image. Sixty samples were randomly selected as
      calibration set, and the remaining 30 samples formed prediction set. The full
      spectrum and water contents were correlated using partial least squares
      regression (PLSR) and least-squares support vector machines (LS-SVM), which were
      then applied to predict water contents for prediction samples. A novel variable
      extraction method called random frog was applied to select effective wavelengths
      (EWs) from the full-spectrum. PLSR and LS-SVM calibration models were established
      respectively to detect water contents in salmon based on the EWs. Though the
      performances of EWs-based models were worse than models using full-spectrum, only
      12 wavelengths were used to substitute for the original 151 wavelengths, thus
      models were greatly simplified and more suitable for practical application. For
      EWs-based PLSR and LS-SVM models, satisfactory results were achieved with
      correlation coefficient of prediction (Rp) of 0. 92 and 0. 93 respectively, and
      root mean square error of prediction (RMSEP) of 1. 31% and 1. 18% respectively.
      The results indicated that near-infrared hyperspectral imaging combined with
      chemometrics allows accurate prediction of water contents in salmon flesh,
      providing important reference for the rapid inspection of fish quality.

PMID- 25993832
TI  - [Characteristics of Raman spectra of minerals in the veins of Wenchuan earthquake
      fault zone].
AB  - Quartz in the veins at the Shenxigou section of Wenchuan earthquake fault zone
      was investigated by micro-Raman spectroscopic measurement, and the distribution
      of compressive stress in the fault zone was estimated by the frequency shifts of
      the 464 cm-1 vibrational mode of quartz grains in the veins. It was showed that
      the 464 cm-1 peak arising from the quartz grains in the veins near the fault
      plane shifts by 3. 29 cm-1 , and the corresponding compressive stress is 368. 63
      MPa, which is significantly lower than the stress accumulation on both sides due
      to multi-stage events. Stress accumulation increased with moving away from the
      fault plane in the footwall with the offset of the 464 cm-1 peak arising from the
      quartz grains in the veins increasing, which can reach 494. 77 MPa at a distance
      of 21 m with a high offset of 4. 40 cm-1 of the 464 cm-1 peak. The compressive
      stress gets the maximum value of 519.87 MPa at a distance of 10 m from the fault
      plane in the hanging wall with the offset of the 464 cm-1 peak arising from the
      quartz grains in the veins being 4. 62 cm-1, followed by a sudden drop in stress
      accumulation, and it drops to 359. 59 MPa at a distance of 17 m. Because of
      moving away from the foult plane at the edge of the foult zone, the stress drops
      to 359. 59 MPa with a small value of 464 cm-1 peak offset 3. 21 cm-1 at a
      distance of 27 m from the fault plane in the hanging wall due to the little
      effect by the fault activity. Therefore, the stress of Wenchuan earthquake fault
      zone is partially released, but the rest of the stress distribution is uneven,
      and there is also a high stress accumulation in somewhere in the fault zone,
      which reflects that the mechanical properties of the rocks in the fault zone have
      a characteristic of unevenness in space.

PMID- 25993833
TI  - [Raman spectra calculation and analysis of plasticizer dioctyl phthalate].
AB  - In recent years, with frequent domestic food safety incidents related to the
      plasticizing agent, the detection of plasticizers in food research becomes
      increasingly urgent. DEHP is one of the plasticizer. In the present paper,
      theoretical Raman spectrum and experimental Raman spectrum of DEHP were given.
      DEHP molecular structure was optimized by DFT(B3LYP) method. DEHP molecular Raman
      spectra and infrared spectra were calculated with. HF theory and DFT theory based
      on 3-2G level. The analytical reagent level DEHP Raman spectra was measured, and
      was compared with theoretical spectra, and good agreements were obtained between
      the theoretical and experimental results. Because of different calculation
      methods, we can see that both the wave number and relative intensity of peaks
      have small differences. DEHP structure parameters were also given in the paper
      including bond lengths and bond angles etc. Vibrational modes were assigned to
      all bands between 400 and 3 500 cm-1. Raman spectroscopy study of the commonly
      used plasticizer dioctyl phthalate was reported in this paper for the first time.
      This effort will contribute to the research and application of Raman spectroscopy
      in the field of food testing.

PMID- 25993834
TI  - [Using Raman spectrum analysis to research corrosive productions occurring in
      alloy of ancient bronze wares].
AB  - The present paper analyzes the interior rust that occurred in bronze alloy sample
      from 24 pieces of Early Qin bronze wares. Firstly, samples were processed by
      grinding, polishing and ultrasonic cleaning-to make a mirror surface. Then, a
      confocal micro-Raman spectrometer was employed to carry out spectroscopic study
      on the inclusions in samples. The conclusion indicated that corrosive phases are
      PbCO3 , PbO and Cu2O, which are common rusting production on bronze alloy. The
      light-colored circular or massive irregular areas in metallographic structure of
      samples are proved as Cu2O, showing that bronze wares are not only easy to be
      covered with red Cu2O rusting layer, but also their alloy is easy to be eroded by
      atomic oxygen. In other words, the rust Cu2O takes place in both the interior and
      exterior parts of the bronze alloy. In addition, Raman spectrum analysis shows
      that the dark grey materials are lead corrosive products--PbCO3 and PbO, showing
      the corroding process of lead element as Pb -->PbO-->PbCO3. In the texture of
      cast state of bronze alloy, lead is usually distributed as independent particles
      between the different alloy phases. The lead particles in bronze alloy would have
      oxidation reaction and generate PbO when buried in the soil, and then have
      chemical reaction with CO3(2-) dissolved in the underground water to generate
      PbCO3, which is a rather stable lead corrosive production. A conclusion can be
      drawn that the external corrosive factors (water, dissolved oxygen and carbonate,
      etc) can enter the bronze ware interior through the passageway between different
      phases and make the alloy to corrode gradually.

PMID- 25993835
TI  - [A purple-emitting luminescence complex [Cd(bpdc)(phen)2(H2O)] . 6H2O: synthesis,
      structure and spectral properties].
AB  - A supramolecular Cd(II) complex[Cd(bpdc) (phen)2 (H2O)] . 6H20 (1) was
      synthesized with 2, 4'-biphenyldicarboxylic acid (H2bpdc) and 1, 10
      phenanthroline (phen) under hydrothermal conditions and characterized by single
      crystal X-ray diffraction elemental analysis, and IR spectrum. Single-crystal X
      ray analysis reveals complex 1 crystalizes in the triclinic P 1 space group, the
      metal center Cd(II) ion is six-coordinated and exhibits a distorted octahedron
      geometry arrangement. 3D supramolecular structure could be formed taking into
      account two kinds of hydrogen bonds and pi--pi interactions. At the same time, we
      discussed the luminescent properties of complex 1 in the solid-state as well as
      in the solvents at different temperatures. When excited at 350 nm, in the solid
      state at 298 K, 1 has purple luminescence with emission band at 390 nm; in the
      solid state at 77 K, 1 displays two emission bands at 380 and 520 nm. Because the
      vibration structure is more defined at low temperature, at 298 K, 1 also has
      purple luminescence in DMSO and CH3OH solutions with emission bands at 380 and
      375 nm, which are blue-shifted compared with solid-state maximum emission band.
      These all can be attribute to the pi*-->pi transition based on the coordinate
      ligands. The fluorescence decay curves of complex 1 indicate that the processes
      of decay consist of two components. At 298 K, the lifetime of 1 is longer in DMSO
      solution (tau1 =1. 73 us and tau2 =14. 07 us) than that in CH3OH solution (tau1
      =1. 21 us and tau2 = 12. 44 us). Moreover, the-lifetime of 1 is longer at 77 K
      (tau1 =1. 96 us and tau2= 16. 11 us) than that at 298 K in the solid state (tau1=
      1. 20 us and tau2 =11. 34 us). The results might be caused by the increase in
      radiative rate and decrease in non-radiative rate at low temperature.

PMID- 25993836
TI  - Development and validation of UV spectrophotometric method to study stress
      degradation behaviour of rizatriptan benzoate.
AB  - Rizatriptan benzoate is a 5 HT 1B/1D receptor agonist which is prescribed for the
      treatment of migraine. In the present study new, simple, specific ultraviolet
      spectrophotometric method for rizatriptan benzoate was developed and validated.
      Forced degradation studies were carried out in acidic, alkaline and neutral pH
      conditions. The absorbance maxima peak was found to be 224 nm and linearity was
      observed in the concentration range of 0. 5-2. 5 ug . mL-1 with regression
      coefficient value of 0. 998 8. The method was validated and found to be precise.
      The percent recovery for rizatriptan benzoate was found to be 98. 576+/-0. 202.
      The bulk drug was found to be stable in neutral and acidic pH conditions but got
      degraded in 1 N NaOH solution.

PMID- 25993837
TI  - [The fluorescence characteristics of dissolved organic matter (DOM) in the
      seagrass ecosystem from Hainan by fluorescence excitation-emission matrix
      spectroscopy].
AB  - The fluorescence characteristics of dissolved organic matter (DOM) were
      determined in the seagrass ecosystem collected in Xincun Bay of Hainan Island in
      late January, 2013, using fluorescence excitation-emission matrix spectroscopy
      (EEMs). EEMs spectra showed 2 types of fluorescence signals in DOM samples, three
      hurnic-like fluorescence peaks and two protein-like fluorescence peaks,
      respectively. The former included UVC peak A (Ex/Em: 230/430 nm), UVA peak C
      (Ex/Em: 350/440 nm), and UVA peak M (Ex/Em: 300/380-400 nm), while the latter
      included tryptophan-like peaks R (Ex/Em: 230/355 - 375 nm) and N (Ex/Em: 280
      300/365-380 nm). Peak N was more like a combination of Peak M and Peak R.
      Moreover, free tyrosine-like molecules in DOM from the seagrass-beds ecosystem
      did not exist because the tyrosine-like fluorescence was not found. There were
      significant positive correlations of peak N with M and R (0. 97 and 0. 54 for R2,
      respectively), and peak A with C (0. 86 for R2), showing their same sources and
      biogeochemical behaviors. The change law of mean fluorescence intensities of
      those fluorescence signals was R (0. 304 RU) >A (0. 194 RU) >M (0. 147 RU) >N (0.
      125 RU) >C (0. 051 RU). And, higher . L-1 concentrations of all the fluorescence
      occurred in the coastal waters inshore, with low values in two small regions
      located in the southwest and southeast of the bay where the seagrasses
      flourished. The distributions of those fluorescence signals in Xincun Bay
      suggested that the dynamics responsible for the humic-like fluorescence might be
      the same as that responsible for the protein-like fluorescence. The high
      fluorescence index (FI: 1. 81), high biological index (BIX: 1. 44) and low
      humification index (HIXa: 4. 2 and HIXb: 0. 81) showed that the DOM from the
      seagrass-dominant ecosystem has a strong autochthonous contribution and poor
      humification degree. The results clearly suggested that the DOM in this region
      has a rather unique fluorescence characteristic and is quite different from other
      aquatic environments.

PMID- 25993838
TI  - [Synthesis and characterization of non fluorescent ZnS nano clusters].
AB  - Zinc sulfide nano clusters were synthesized and characterized. A kind of method
      using zinc sulfide nanoparticles cluster cation exchange reaction(CX) to detect
      trace biological molecules was established. Non fluorescent ZnS nanoparticles
      (NCCs) were synthesized and characterized. The property of nano clusters directly
      influences the detection results. Through transmission electron microscopy images
      and X-ray diffraction, nano clusters which could quickly release a mass of Zn2+
      from rapid cation exchange reaction were known to be porous and generate
      fluorescence signal under the action of zinc reagent. The external crystal
      arranges loosely compared to the internal, which is conducive to rapid cation
      exchange, and the crystal size is related to heating time. It was demonstrated
      that the smallest nanocluster had a relative large surface area and higher
      cationic exchange efficiency through the determination of the specific surface
      area of nano clusters for detecting surface area and pore size. Three methods
      (acid dissolution method, cation exchange and micro wave aided by cation
      exchange) which effected Zn2+ release performance were experimented. It turned
      out that microwave auxiliary cation exchange method had high SNR, simple
      operation, and could be used in zinc sulfide nanoparticle immunoassay. Having
      compared the relations between the release efficiency, target binding force of
      ZnZ2+ and its average diameter, the results show that the nano cluster size of 44
      nm exhibits the highest cation exchange efficiency. All these features make the
      ZnS nanocluster cation exchange amplifier to be a highly sensitive, fairly
      biocompatible, low-cost and environment friendly detection tool in the detection
      of biomolecules.

PMID- 25993839
TI  - Application of a new spectrophotometric method manipulating ratio spectra for
      determination of bambuterol hydrochloride in the presence of its degradation
      product terbutaline.
AB  - A simple, specific, accurate and precise spectrophotometric stability indicating
      method is developed for determination of bambuterol hydrochloride (BH) in the
      presence of its degradation product terbutaline (TERB) and in pharmaceutical
      formulations. A newly developed spectrophotometric method called ratio difference
      method by measuring the difference in amplitudes between 245 and 260 on of ratio
      spectra. The calibration curves are linear over the concentration range of 0. 1 -
      1 mg . mL-1 for BH and 0. 1-0. 7 mg . mL-1 for TERB with mean percentage recovery
      of 100. 56 +/- 0. 751 and 99. 88 +/- 1. 183, respectively. The selectivity of the
      proposed method is checked using laboratory prepared mixtures. The proposed
      method has been successfully applied to the analysis of BH in pharmaceutical
      dosage forms without interference from other dosage form additives and the
      results have been statistically compared with pharmacopeial method.

PMID- 25993840
TI  - [Effects of glycerol on the spectral properties of sodium caseinate].
AB  - Although the immigration of water molecule, and diffusion and traversing of
      oxygen can be prevented by the edible film prepared through sodium caseinate,
      which plays a good protection role for the food, the strong hydrophilicity makes
      its watertightness and mechanical properties become inferior. Because the
      toughness and water resistance of SC films can be enhanced by glycerol (G) as an
      additive, it is necessary to elucidate the interaction between G and SC through
      the spectral characteristics such as fluorescence spectra, infrared spectra and
      UV spectra. The results show that the fluorescence intensity of SC decreases due
      to the addition of G. The binding constant obtained by the double logarithmic
      regression curve analysis is 1. 127 x 10(3) L . mol-1 and the number of binding
      sites reaches 1. 161. It indicates that the weak chemical bond is primary between
      G and SC molecules; From IR the absorption peaks of SC are almost the same before
      and after adding G. However, there is a certain difference among their absorption
      intensities. It reveals that the secondary structure of SC is affected, beta
      folding length decreases, alpha helix, random coil structure, beta angle
      structure increases, and the intermolecular hydrogen bond is strengthened; From
      UV the peptide bond structure of SC is not changed after the addition of G, but
      the polymer with larger molecular weight, which is formed by non-covalent bond,
      makes the peak intensity decrease. The research gives the mode of G and SC from
      the molecular level.

PMID- 25993841
TI  - [EEMD de-noising of reflecting spectrum in soil profiles].
AB  - In the present paper, based on the multi-resolution attribute of EEMD (ensemble
      empirical mode decomposition) method, we presented a new de-noising method for
      analyzing spectrum, and applied it to process the reflecting spectrum data of 33
      soil profiles in the typical oasis located in the middle reaches of the Tarim
      River. To explore the de-noising effect of EEMD threshold method for reflecting
      spectrum in soil profiles; we compared EEMD threshold method with wavelet
      transform method. The results showed that compared with traditional wavelet
      transform method, the signal to noise ratio (SNR) was improved from 14. 8366 to
      34. 2757 dB, and the root mean square error (RMSE) was reduced to 7. 2406 X 10(
      6) from 6. 7861 X 10(-5) and the correlation coefficient (r) increased from 0.
      9825 to 0. 9998. Therefore, three de-noising effect indicators of EEMD threshold
      method are better than those of wavelet transform method. This proved that the
      EEMD threshold method can effectively eliminate the noise of soil-profile
      spectrum and also preserve the detailed information of the original spectra well.
      Thus, the analysis precision of the spectrum will be improved. In addition, by
      contrast with the wavelet threshold method, the EEMD threshold method is adaptive
      and is fairly reliable. As a new method for spectral pretreatment, the EEMD
      threshold method will have a good application prospect in spectra de-noising.

PMID- 25993842
TI  - [A inversion model for remote sensing of leaf water content based on the leaf
      optical property].
AB  - Leaf water content is a fundamental physiological characteristic parameter of
      crops, and plays an important role in the study of the ecological environment.
      The aim of the work reported in this paper was to focus upon the retrieval of
      leaf water content from leaf-scale reflectance spectra by developing a physical
      inversion model based on the radiative transfer theory and wavelet analysis
      techniques. A continuous wavelet transform was performed on each of leaf
      component specific absorption coefficients to pick wavelet coefficients that were
      identified as highly sensitive to leaf water content and insensitive to other
      components. In the present study, for identifying the most appropriate wavelet,
      the six frequently used wavelet functions available within MATLAB were tested.
      Two biorl. 5 wavelet coefficients observed at the scale of 200 nm are provided
      with good performance, their wave-length positions are located at 1 405 and 1 488
      nm, respectively. Two factors (alpha and Delta) of the predictive theoretical
      models based on the biorl. 5 wavelet coefficients of the leaf-scale reflectance
      spectra were determined by leaf structure parameter N. We built a database
      composed of thousands of simulated leaf reflectance spectra with the PROSPECT
      model. The entire dataset was split into two parts, with 60% the calibration
      subset assigned to calibrating two factors (alpha and Delta) of the predictive
      theoretical model. The remaining 40% the validation subset combined with the
      LOPEX93 experimental dataset used for validating the models. The results showed
      that the accuracy of the models compare to the statistical regression models
      derived from the traditional vegetation indices has improved with the highest
      predictive coefficient of determination (R2) of 0. 987, and the model becomes
      more robust. This study presented that wavelet analysis has the potential to
      capture much more of the information contained with reflectance spectra than
      previous analytical approaches which have tended to focus on using a small number
      of optimal wavebands while discarding the majority of the spectrum.

PMID- 25993843
TI  - [Simulation of TDLAS direct absorption based on HITRAN database].
AB  - Simulating of the direct absorption TDLAS spectrum can help to comprehend the
      process of the absorbing and understand the influence on the absorption signal
      with each physical parameter. Firstly, the basic theory and algorithm of direct
      absorption TDLAS is studied and analyzed thoroughly, through giving the
      expressions and calculating steps of parameters based on Lambert-Beer's law, such
      as line intensity, absorption cross sections, concentration, line shape and gas
      total partition functions. The process of direct absorption TDLAS is simulated
      using MATLAB programs based on HITRAN spectra database, with which the
      absorptions under a certain temperature, pressure, concentration and other
      conditions were calculated, Water vapor is selected as the target gas, the
      absorptions of which under every line shapes were simulated. The results were
      compared with that of the commercial simulation software, Hitran-PC, which showed
      that, the deviation under Lorentz line shape is less than 0. 5%, and that under
      Gauss line shape is less than 2. 5%, while under Voigt line shape it is less than
      1%. It verified that the algorithm and results of this work are correct and
      accurate. The absorption of H2O in v2 + v3 band under different pressure and
      temperature is also simulated. In low pressure range, the Doppler broadening
      dominant, so the line width changes little with varied.pressure, while the line
      peak increases with rising pressure. In high pressure range, the collision
      broadening dominant, so the line width changes wider with increasing pressure,
      while the line peak approaches to a constant value with rising pressure. And
      finally, the temperature correction curve in atmosphere detection is also given.
      The results of this work offer the reference and instruction for the application
      of TDLAS direct absorption.

PMID- 25993844
TI  - [Research on maize multispectral image accurate segmentation and chlorophyll
      index estimation].
AB  - In order to rapidly acquire maize growing information in the field, a non
      destructive method of maize chlorophyll content index measurement was conducted
      based on multi-spectral imaging technique and imaging processing technology. The
      experiment was conducted at Yangling in Shaanxi province of China and the crop
      was Zheng-dan 958 planted in about 1 000 m X 600 m experiment field. Firstly, a 2
      CCD multi-spectral image monitoring system was available to acquire the canopy
      images. The system was based on a dichroic prism, allowing precise separation of
      the visible (Blue (B), Green (G), Red (R): 400-700 nm) and near-infrared (NIR,
      760-1 000 nm) band. The multispectral images were output as RGB and NIR images
      via the system vertically fixed to the ground with vertical distance of 2 m and
      angular field of 50 degrees . SPAD index of each sample was'measured
      synchronously to show the chlorophyll content index. Secondly, after the image
      smoothing using adaptive smooth filtering algorithm, the NIR maize image was
      selected to segment the maize leaves from background, because there was a big
      difference showed in gray histogram between plant and soil background. The NIR
      image segmentation algorithm was conducted following steps of preliminary and
      accuracy segmentation: (1) The results of OTSU image segmentation method and the
      variable threshold algorithm were discussed. It was revealed that the latter was
      better one in corn plant and weed segmentation. As a result, the variable
      threshold algorithm based on local statistics was selected for the preliminary
      image segmentation. The expansion and corrosion were used to optimize the
      segmented image. (2) The region labeling algorithm was used to segment corn
      plants from soil and weed background with an accuracy of 95. 59 %. And then, the
      multi-spectral image of maize canopy was accurately segmented in R, G and B band
      separately. Thirdly, the image parameters were abstracted based on the segmented
      visible and NIR images. The average gray value of each channel was calculated
      including red (ARed), green (AGreen), blue (ABlue), and near-infrared (ANIR).
      Meanwhile, the vegetation indices (NDVI (normalized difference vegetation index),
      RVI (ratio vegetation index); and NDGI(normalized difference green index)) which
      are widely used in remote sensing were applied. The chlorophyll index detecting
      model based on partial least squares regression method (PLSR) was built with
      detecting R2=0. 5960 and predicting R2= 0. 568 5. It was feasible to diagnose
      chlorophyll index of maize based on multi-spectral images.

PMID- 25993845
TI  - [Interaction of fish collagen peptide with epigallocatechin gallate].
AB  - Fish collagen is known to have good moisturising property and antioxidant
      ability, which has been increasingly added into cosmetics, foods and drinks as
      thicker agent and to increase dietary supply of collagen. Fish collagen peptide
      (FCP) is a white or pale yellow powder, obtained by extracting collagen from
      sources including the scales and bones of fish such as bonito, halibut, tuna, and
      sea bream. It is identical to human collagen and 100% absorbable through the
      skin. (-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea,
      has lots of beneficial biological and pharmacological effects, including
      antioxidant, antimutagenic, antiviral and antiinflammatory activities. Because
      proteins have the desirable formulation of EGCG-fortified food, the interaction
      between proteins and EGCG molecules has been widely studied. At the same time,
      the interaction of proteins and EGCG was known to affect the content of free
      EGCG, structure of proteins, antioxidant capacity of EGCG in foods. But, to our
      knowledge, the interaction between FCP and EGCG has not been characterised
      clearly, and little is known about their interaction mechanism. Therefore, a
      better understanding of the interaction between FCP and EGCG would help to
      control their functional properties in food products during processing,
      transportation and storage when we facilitate FCP as the vehicles for EGCG. In
      view of the above, we planned to study the interaction of FCP with EGCG by using
      different spectroscopic techniques, such as fluorescence spectroscopic, FTIR, CD
      and Raman. EGCG caused a concentration dependent quenching of the intrinsic
      fluorescence of tyrosine residue in the FCP, indicating the occurrence of
      interactions between FCP and EGCG. Excimer-like species and dityrosine were
      regularly formed with the addition of EGCG into the solution, and the interaction
      of FCP and EGCG partly disrupted the structure-of the protein. Synchronous
      fluorescence results indicate that the interaction caused decrease of the
      polarity around tyrosine residues resulting in FCP conformation alteration. FTIR
      showed that the frequency of 3 281 and 1 248 cm-1 declined, the absorption peaks
      at 3 076 and 1 547 cm-1 had a slight red-shift, the absorption peaks at 1 659 and
      1 689 cm-1 had a slight blue-shift in the FCP-EGCG complexes. It is interesting
      to observe that the CD intensity of FCP around 198 nm decreased with high EGCG
      concentration, and the peak maximum shifted to a larger wavelength (red shift).
      Raman spectra showed that peaks at 863 and 932 cm-1 had a slight red-shift, and
      decreased intensities near 932 cm-1 suggested that more exposure of proline when
      FCP-EGCG complexes formed. This study provides a theoretical basis for fortifying
      FCP products with EGCG.

PMID- 25993846
TI  - [Colorimetric assay of perfluorooctanesulfonate based on gold nanoparticles].
AB  - For the property of persistent, bioaccumulation and genetic toxicity,
      perfluorooctanesulfonate (PFOS) is classified as a sort of persistent organic
      pollutants (POPs). It is significant to develop a novel assay for the
      determination of PFOS. In this work, we create a new colorimetric assay for PFOS
      in which the positively-charged gold nanoparticles (AuNPs) work as a nano-probe.
      This method works on the aggregation of AuNPs induced by PFOS via electrostatic
      interaction. The stable monodisperse AuNPs coated by cysteamine present color of
      red wine and the addition of PFOS can make the monodispersed AuNPs aggregated
      resulting in the color change from wine red to reddish purple with a red-shift in
      ultraviolet-visible absorption spectrum. The experimental results show that AuNPs
      has a characteristic absorption peak (524 nm), as well as a wide absorption peak
      (650 nm) and the absorption signal intensity is proportional to the PFOS content
      in a range of 0. 8-8. 0 umo .l L-1. According to these, we developed a method
      based on ultraviolet-visible absorption and colorimetric to detect PFOS with the
      detection limit of 80 nmol . L-1. The scanning electron microscope (SEM) was
      investigated and the photos show that the stable AuNPs are made and the degree of
      AuNPs aggregation is related with PFOS concentration. The effect tests of
      coexisting substances in system show that common anions had less impact on the
      system and inorganic metal ions had some interference, which can be get rid of by
      cat- ion exchange resin in real sample. This assay was applied to detect PFOS in
      tap water with a recovery range of 87. 5%-118% and RSD 4. 4%. It is a novel
      application of AuNPs-based probe for PFOS detection. The proposed method has more
      advantages such as rapidity, low-cost and simplicity than conventional ones. In
      addition, it has the visual sensing function and the difference of color can be
      sensed by naked eyes directly, which produce ideas of real-time colorimetric
      strategies of nanoprobe application in environmental pollutant detection.

PMID- 25993847
TI  - [Spectrophotometric determination of aromatic amino compounds with J-acid].
AB  - The problems such as chromogenic reaction selectivity, reaction rate, sensitivity
      and water-solubility of azo compounds were considered. The molecular structures
      of coupling components were theoretically designed and screened in the present
      research The reaction conditions and methods of chromogenic reaction were
      investigated. J-Acid (2-amino-5-naphthol-7-sulfonic acid) as a coupling reagent
      to determine aromatic amino compounds was established. In the presence of
      potassium bromide, at room temperature, nitrite reacted with aromatic amino
      compounds in the medium of thin hydrochloric acid. Then diazonium salt reacted
      with J-Acid in the aqueous solution of sodium carbonate, forming coloured azo
      dye, which had a maximum adsorption at 480 nm. The molar adsorption coeffcients
      of aniline, 4-aminobenzene sulfonic acid and 1-naphthylamine were 3. 95 X 10(4),
      3. 24 X 10(4) and 3. 91 X 10(4) L . mol-1 . cm-1 , respectively. Experimental
      results showed that common coexisting ions on the surface water did not affect
      the results of determination. J-Acid of spectrophotometry was used to determine
      the samples of Shanghai Fu Xing Dao canal. Meanwhile, recovery experiments by
      standard addition method were done. Experiment results showed that the recoveries
      of aniline were in the range of 98. 5%-102. 1%, and RSD was 2. 08%. J-Acid is a
      common organic reagent. It is soluble in water and low volatile, and its toxicity
      is much lower than N-ethylenediamine. spectrophotometric determination of
      aromatic amino compounds by J-Acid has the advantage of high sensitivity, good
      selectivity, simple rapid operation and accurate results, and thus it can be used
      for the determination of trace aromatic amino compounds in the environmental
      water.

PMID- 25993848
TI  - [Non-destructive detection research for hollow heart of potato based on semi
      transmission hyperspectral imaging and SVM].
AB  - The quality of potato is directly related to their edible value and industrial
      value. Hollow heart of potato, as a physiological disease occurred inside the
      tuber, is difficult to be detected. This paper put forward a non-destructive
      detection method by using semi-transmission hyperspectral imaging with support
      vector machine (SVM) to detect hollow heart of potato. Compared to reflection and
      transmission hyperspectral image, semi-transmission hyperspectral image can get
      clearer image which contains the internal quality information of agricultural
      products. In this study, 224 potato samples (149 normal samples and 75 hollow
      samples) were selected as the research object, and semi-transmission
      hyperspectral image acquisition system was constructed to acquire the
      hyperspectral images (390-1 040 nn) of the potato samples, and then the average
      spectrum of region of interest were extracted for spectral characteristics
      analysis. Normalize was used to preprocess the original spectrum, and prediction
      model were developed based on SVM using all wave bands, the accurate recognition
      rate of test set is only 87. 5%. In order to simplify the model
      competitive.adaptive reweighed sampling algorithm (CARS) and successive
      projection algorithm (SPA) were utilized to select important variables from the
      all 520 spectral variables and 8 variables were selected (454, 601, 639, 664,
      748, 827, 874 and 936 nm). 94. 64% of the accurate recognition rate of test set
      was obtained by using the 8 variables to develop SVM model. Parameter
      optimization algorithms, including artificial fish swarm algorithm (AFSA),
      genetic algorithm (GA) and grid search algorithm, were used to optimize the SVM
      model parameters: penalty parameter c and kernel parameter g. After comparative
      analysis, AFSA, a new bionic optimization algorithm based on the foraging
      behavior of fish swarm, was proved to get the optimal model parameter (c=10. 659
      1, g=0. 349 7), and the recognition accuracy of 10% were obtained for the AFSA
      SVM model. The results indicate that combining the semi-transmission
      hyperspectral imaging technology with CARS-SPA and AFSA-SVM can accurately detect
      hollow heart of potato, and also provide technical support for rapid non
      destructive detecting of hollow heart of potato.

PMID- 25993849
TI  - [Enhancement effect of double-beam laser processed aqueous solution on ICP
      emission spectrum].
AB  - In order to change the physical properties of aqueous solution and improve the
      radiation intensity of the ICP emission spectrum, the effects of different laser
      power density and irradiation time on the surface tension and viscosity of
      aqueous solution were investigated by using near infrared laser at 976 nm and CO2
      laser at 10. 6 um to irradiate aqueous solution orthogonally, then the
      enhancement of ICP spectral intensity with processed solution was discussed. The
      results showed that the surface tension and viscosity of aqueous solution reduced
      by 42. 13% and 14. 03% compared with the untreated, and the atomization
      efficiency increased by 51.26% at the laser power density 0. 265 7 W . cm-2 of
      976 nm and 0. 206 9 W . cm-2 of CO2 laser with 40 min irradiation time. With the
      optimized aqueous solution introduced into the ICP source, the spectral line
      intensity of sample elements As, Cd, Cr, Hg and Pb was enhanced by 46.29%, 94.
      65%, 30. 76%, 33.07% and 94. 58% compared to the untreated aqueous solution,
      while the signal-to-background ratio increased by 43. 84%, 85. 35%, 28. 71%, 34.
      37% and 90. 91%, respectively. Plasma temperature and electron density also
      increased by 5. 94% and 1. 18% respectively. It is obvious that the method of
      double-beam laser orthogonal irradiation on solution can reduce the surface
      tension and viscosity of aqueous solution significantly, and raise the
      radiationintensity of ICP source, and will provide a better condition for
      detecting the trace heavy metal elements in water samples.

PMID- 25993850
TI  - [Analysis of lead in unknown samples based on the standard addition method using
      laser induced breakdown spectroscopy].
AB  - The standard addition method with laser induced breakdown spectroscopy was used
      to analyze an unknown sample taken from a lead battery factory. the matrix
      influence on the results was effectively avoided when the external or internal
      standard method was used, and the pretreatment of samples was simple and quick.
      The Nd ' YAG pulse laser with wavelength 1 064 nm was used as the excitation
      source. The echelle spectroscopy with high resolution and wide spectral range was
      used as the spectral separation device, and the intensified charge coupled device
      (ICCD) as the spectral detection device in the experiment. The characteristic
      line at 405. 78 nrn was chosen as the analysis line to measure Pb concentration.
      Fe I : 404. 58 line was chosen as the internal standard. Pre-experiment was
      carried out to confirm the appropriate condition. Under the laser energy of 128.
      5 mJ, the delay time of 2. 5 tps, and the gate width of 3 ps, it was determined
      that with the addition of Pb to the sample in the range of 0 and 25 000 mg . kg
      1, there wasn't self-absorption. There was a good linear relationship between the
      intensity of the spectral line of 405. 78 nm and the addition of Pb. The
      appropriate concentration of Pb added into the sample for analysis was determined
      by this series of samples. On this basis, four samples were prepared with three
      parallel samples for each sample in order to verify the repeatability and
      reliability of the method, i. e. 5 000, 10 000, 15 000, 20 000 mg . kg-1 Pb was
      added into the original sample. The results were compared with the result of ICP
      MS. The twelve samples' relative errors were between -24. 6% and 17. 6%. The
      average result was 43 069 mg . kg-1 with the relative error -2. 44%.

PMID- 25993851
TI  - [Application of ICP-MS method in the determination of mineral elements in vitex
      honey for the classification of their geographical origins with chemometric
      approach].
AB  - In the present work, the contents of 38 elements of 65 vitex (Vitex negundo var.
      heterophylla Rehd. ) honey samples from Shunyi of Beijing, Fuping and Pingshan of
      Hebei province were determined by inductively coupled plasma mass spectrometry
      (ICP-MS). Among them, B, Na, Mg, P, K, Ca, Fe and Zn were the most abundant
      elements with mean contents more than 1 mg kg-1. It can be found that there were
      relationships between the contents of elements and the geographical origin of
      vitex honey samples. Taking the contents of 29 out of 38 mineral elements (Na,
      Mg, Al, K, Ti, V, Mn, Fe, Ni, Cu, Zn, Ga, As, Sr, Y, Mo, Cd, Ba, La, Ce, Pr, Nd,
      Sm, Gd, Dy, Ho, T1, Pb and U) as variables, the chemometric methods, such as
      principal component analysis (PCA) and back-propagation artificial neural network
      (BP-ANN), were applied to classify vitex honey samples according to their
      geographical origins. PCA reduced all of the variables to four principal
      components and could explain 81. 6% of the total variances. The results indicated
      that PCA could mainly classify the vitex honey samples into three groups. BP-ANN
      was explored to construct classification model of vitex honeys according to their
      geographical origin. For the whole data set, the overall correct classification
      rate and cross-validation (leave one out method) rate of proposed BP-ANN model
      was 100% and 95. 4%, respectively. To further test the stability of the model
      developed for prediction, 75% of honey samples of each geographical origin were
      randomly selected for the model training set, and the remaining samples were
      classified with the use of the constructed model. Both the overall correct
      classification rate and prediction rate of proposed BP-ANN model were 100%. It is
      concluded that the profiles of multi-element by ICP-MS with chemometric methods
      could be a potential and powerful tool for the classification of vitex honey
      samples from different geographical origins.

PMID- 25993852
TI  - [Application of inductively coupled plasma mass spectrometry with chemometric
      methods in classification of honeys according to their types].
AB  - In order to identify honeys according to their floral origin, inductively coupled
      plasma mass spectrometry (ICP-MS) combined with principal component analysis
      (PCA) and discriminant analysis (DA) were employed in the present study. Three
      kinds of honeys such as acacia honey samples, sunflower honey samples and rape
      honey samples were selected. It was pretreated by wet-acid digestionand measured
      20 kinds of mineral elements in honey samples by ICP-MS. The result showed that
      the accuracy of the inductively coupled plasma mass spectrometrymeted the
      requirements. The result of principal component analysis demonstrated that the
      acacia honey samples were performed a trend of certain gather. The trend of the
      sunflower honey samples and the rape honey samples are not obvious. Ten kinds of
      mineral elements including Na, Mg, K, Ca, Sr, Ba, V, Fe, Ni, Sb can be regarded
      as honey varieties of characteristic elements. Seven kinds of mineral elements
      such as Mg, Sr, Ba, Sb, Ni, Cr and Na could be selected through stepwise
      discriminant analysis. Using bayes discriminant analysis, A linear discriminant
      function can be recieved. The discrimination rate of honey samples such as acacia
      honey samples, sunflower samples and rape honey samples were 100%, 80% and 90. 9%
      respectively. Two sunflower honey samples was misclassified into rape honey
      samples an-done rape honey samples are also misclassified into acacia honey
      sample. The total rate of discriminant model cross validation was 90. 3%. It is
      concluded that the mineral elements in honey varieties with good classification.
      The present study can provide theoretical basis and the relationship between
      thetypes of honey samples with mineral elements. The method what this study used
      had simple, accurate and stablecharacteristics, which can be used as a reliable
      method of honey sample identification.

PMID- 25993853
TI  - [Determination of high concentrations of rubidium chloride by ICP-OES].
AB  - The method of ICP-OES for the direct determination of high content of rubidium in
      rubidium chloride solutions was studied through mass dilution method and
      optimizing parameters of the instrument in the present paper. It can reduce the
      times of dilution and the error introduced by the dilution, and improve the
      accuracy of determination results of rubidium. Through analyzing the sensitivity
      of the three detection spectral lines for rubidium ion, linearly dependent
      coefficient and the relative errors of the determination results, the spectral
      line of Rb 780. 023 nm was chosen as the most suitable wavelength to measure the
      high content of rubidium in the rubidium chloride solutions. It was found that
      the instrument parameters of ICP-OES such as the atomizer flow, the pump speed
      and the high-frequency power are the major factors for the determination of
      rubidium ion in the rubidium chloride solutions. As we know instrument parameters
      of ICP-OES have an important influence on the atomization efficiency as well as
      the emissive power of the spectral lines of rubidium, they are considered as the
      significant factors for the determination of rubidium. The optimization
      parameters of the instrument were obtained by orthogonal experiments and further
      single factor experiment, which are 0. 60 L . min-1 of atomizer flow, 60 r . min
      1 of pump speed, and 1 150 W of high-frequency power. The same experiments were
      repeated a week later with the optimization parameters of the instrument, and the
      relative errors of the determination results are less than 0. 5% when the
      concentration of rubidium chloride ranged from 0. 09% to 0. 18%. As the
      concentration of rubidium chloride is 0. 06%, the relative errors of the
      determination results are -1. 7%. The determination of lithium chloride and
      potassium chloride in the high concentration of the aqueous solutions was studied
      under the condition of similar instrument parameters. It was found by comparison
      that the determination results of lithium chloride are better than that of
      potassium chloride and rubidium chloride. The method of ICP-OES used for
      determination of high content of rubidium is fast and simple for operation, and
      the results are accurate. It is suitable for studying the equilibrium in the salt
      water system containing rubidium and for analysis of products of rubidium with
      high content.

PMID- 25993854
TI  - [Analysis of changes in minerals contents during cider fermentation process by
      inductively coupled plasma mass spectrometry].
AB  - The changes in mineral elements during cider fermentation process were determined
      using ICP-MS. The results showed that the main minerals in the fermentation
      liquor included K, Na, Ca, Mg, Fe, Mn, Zn, Cu, Sr and B. The content of K was the
      highest in both the apple juice and the cider, being 1 853. 83 and 1 654. 38 mg .
      L-1 respectively. The content of minerals was in dynamic changes along with the
      fermentation process. As a whole, during 72-120 h and 144-216 h, most of the
      minerals contents underwent great fluctuation. Especially when fermented for 192
      h, the content of most of the minerals reached peak value or valley value. The
      content of Fe and Zn achieved their peak value, while the content of K, Na, Ca,
      Mg, Mn and B achieved valley value. But during the following 24 h, the content of
      minerals underwent a sharp reversal. After fermentation, the content of K, Mg,
      Cu, Zn and B decreased significantly, while the content of Na, Ca, Mn, Fe and Sr
      did not change significantly. The correlational analysis was conducted to
      evaluate the correlation between the mineral elements, and the result showed that
      the correlation between Ca and Mn was the most significant, with the correlation
      index reaching 0. 924. The information of this study will supply sufficient data
      for the fermentation process control and quality improvement of cider.

PMID- 25993855
TI  - [Determination of multi-elements in aquatic feed by microwave plasma-atomic
      emission spectroscopy].
AB  - In the present research, a novel method for quantitative analysis of multi
      elements (Cu, Fe, Mn, Zn, K and Na) in aquatic feed was established by using
      microwave plasma-atomic emission spectroscopy (MP-AES) technology. The sample was
      pretreated by traditional dry ashing method, and then a series of methodological
      study experiments, such as the detection limit, the spiked recovery, the
      precision measurement, the method comparison with AAS and ICP-AES, the standard
      substance confirmation and so on, were accomplished by MP-AES. The instrument
      parameters of MP-AES were optimized. In the optimal con- ditions, the linear
      calibration curve was established for each element, and the linear regression
      correlation coefficient was more than 0. 999. The limit of detection (LOD) was
      between 0. 4 and 3. 9 mg . kg-1. The spiked recovery was between 103% and 112%.
      The relative standard deviation of precision measurement was between 0. 2% and 0.
      6%. In the method comparison, the one way ANOVA statistical analysis yielded the
      p value between 0. 065 and 0. 438, which were greater than 0. 05, there was no
      statistically significant difference among MP-AES, AAS and ICP-AES. The FAPAS
      10102 dairy ration test material and the national standard substances (GBW07602)
      were prepared for method confirmation in this study, and the measured values were
      in good agreement with the certified values. Compared with the commercial ICP-AES
      which typically uses argon as the plasma gas, the MP-AES relies on using nitrogen
      as the plasma gas, which may provide a more economical alternative to traditional
      ICP-AES for routine analysis in feed analytical laboratories. The established
      method was simple, fast, reproducible and accurate, and it was an ideal analysis
      technique to substitute AAS and ICP-AES for the determination of multi-elements
      in aquatic feed.

PMID- 25993856
TI  - [In vitro safety evaluation study of Angong Niuhuang Wan].
AB  - To study a vitro extraction method to determine soluble mercury and mercury
      species in Angong Niuhuang Wan and investigate a vitro safety evaluation method,
      the best extraction scheme was determined after a great deal of conditioning
      experiments focusing on how the solvent, purification, duration of extraction and
      purification etc impact on mercury extraction. Soluble mercury was determined by
      inductively coupled plasma mass spectrometry and mercury species were determined
      by high performance liquid chromatography/inductively coupled plasma mass
      spectrometry. Result show that the best extraction method of soluble mercury and
      its species was ultrasonic extraction in artificial intestinal juice at 37 
      degrees C for 2 hours, letting it stand for 20 hours and taking the supermatant.
      The method was reproducible, which could simulate the human body environment to
      maximum extent. Methyl mercury, ethyl mercury and Hg2+ were not found in the
      extracts of Angong Niuhuang, although the content of soluble mercury was high. It
      Was concluded that the method could be applied to the vitro extraction and
      determination of soluble mercury and mercury species in Chinese traditional
      medicines containing cinnabar. Methyl mercury, ethyl mercury and Hg2+ could be
      taken as the targets of in vitro safety evaluation of Angong Niuhuang.

PMID- 25993857
TI  - [Spectroscopic analysis and photocatalytical activity of carbon nitride
      materials].
AB  - Graphited carbon nitride materials (g-C3N4) with high visble-light response were
      synthesized by thermal condensation of melamine at varied temperature. The
      microstructure and optical property of as achieved catalysts were investigated by
      XRD, SEM and UV-Vis techniques, respectively. Moreover, rhodamine B solution was
      applied to measure the catalytical performance under the irradiation of different
      sources of light. The results showed that the major structures of g-C3N4 were
      kept, though lots of blocks were scattered on the surface because of the damage
      of lamellar structure caused by the high temperature. As the thermal temperature
      was increased, the adsorptions of light were greatly enhanced in both UV and Vis
      region, which might be due to the decrease in reflection and the increase in
      refraction at the lumpy surface. In the degradation of rhodamine B solution, all
      the samples showed high photocatalytic activities under the irradiation of both
      Visible-light and sunlight, and 94. 8% (60min, under Vis-light) and 91. 1%
      (90min, under sunlight) of RhB were degraded when the thermal temperature was 580
      degrees C. This research would greatly enlighten the studies of environmental
      purification using clean green energy.

PMID- 25993858
TI  - [Application of calibration curve method and partial least squares regression
      analysis to quantitative analysis of nephrite samples using XRF].
AB  - The authors tried to find a method for quantitative analysis using pXRF without
      solid bulk stone/jade reference samples. 24 nephrite samples were selected, 17
      samples were calibration samples and the other 7 are test samples. All the
      nephrite samples were analyzed by Proton induced X-ray emission spectroscopy
      (PIXE) quantitatively. Based on the PIXE results of calibration samples,
      calibration curves were created for the interested components/elements and used
      to analyze the test samples quantitatively; then, the qualitative spectrum of all
      nephrite samples were obtained by pXRF. According to the PIXE results and
      qualitative spectrum of calibration samples, partial least square method (PLS)
      was used for quantitative analysis of test samples. Finally, the results of test
      samples obtained by calibration method, PLS method and PIXE were compared to each
      other. The accuracy of calibration curve method and PLS method was estimated. The
      result indicates that the PLS method is the alternate method for quantitative
      analysis of stone/jade samples.

PMID- 25993859
TI  - [The study of selecting sample detecting position and lead plate inner material
      in thin film method X-ray fluorescence measurement].
AB  - (1) In this paper type 316 stainless steel metal plate as the research object,
      the selection of sample detecting position was studied when thin film method X
      ray fluorescence measurement was conducted. The study showed that the optimal
      location for the sample detection was sample distance X-ray tube and detector
      baseline 1cm with the baseline into a 16 degrees angle. (2) Heavy metal
      pollutants of Pb, Cd and Cr in industrial ambient air as the main analysis
      object, when thin film method X-ray fluorescence conducted with lead plate
      protection, X-rays will penetrate the membrane and continuely stimulate the
      protective lead plate. Therefore there is lead spectral line interference in the
      filter membrane background spectrum, which will affect the detection of lead
      element in real samples. Studies show that when a layer of isolating material was
      applied between the thin sample and the protective lead plate, the interference
      of lead line can effectively be avoided. (3) Several rigid insulating material of
      type 316 stainless steel, brass, aluminum, red copper and PTEE as lead inner
      material were selected and studied. The study results showed that compared with X
      ray fluorescence spectra of other lead inner materials, the X-ray fluorescence
      spectrum of red copper contained the least element spectral lines. There were not
      Cr, Cd and Pb spectrum peaks in the X-ray fluorescence spectrum of red copper.
      And the target timber scattering spectrum intensity in the high energy part was
      weaker compared to other X-ray fluorescence spectrum. The above analysis shows
      that red copper has the minimal disturbance to the actual measurement of heavy
      metals Cr, Cd and Pb. At the same time, red copper as lead inner materials can
      effectively avoid the interference of lead spectrum line in lead plate. So red
      copper is the best lead plate inner materials in thin film method X-ray
      fluorescence spectroscopy measurement. This study provides an important
      theoretical basis for the assembling and setting'up air and water weight metal X
      ray fluorescence spectrometer.

PMID- 25993860
TI  - [SKLOF: a new algorithm to reduce the range of supernova candidates].
AB  - Supernova (SN) is called the "standard candles" in the cosmology, the probability
      of outbreak in the galaxy is very low and is a kind of special, rare astronomical
      objects. Only in a large number of galaxies, we have a chance to find the
      supernova. The supernova which is in the midst of explosion will illuminate the
      entire galaxy, so the spectra of galaxies we obtained have obvious features of
      supernova. But the number of supernova have been found is very small relative to
      the large number of astronomical objects. The time computation that search the
      supernova be the key to weather the follow-up observations, therefore it needs to
      look for an efficient method. The time complexity of the density-based outlier
      detecting algorithm (LOF) is not ideal, which effects its application in large
      datasets. Through the improvement of LOF algorithm, a new algorithm that reduces
      the searching range of supernova candidates in a flood of spectra of galaxies is
      introduced and named SKLOF. Firstly, the spectra datasets are pruned and we can
      get rid of most objects are impossible to be the outliers. Secondly, we use the
      improved LOF algorithm to calculate the local outlier factors (LOF) of the
      spectra datasets remained and all LOFs are arranged in descending order. Finally,
      we can get the smaller searching range of the supernova candidates for the
      subsequent identification. The experimental results show that the algorithm is
      very effective, not only improved in accuracy, but also reduce the operation time
      compared with LOF algorithm with the guarantee of the accuracy of detection.

PMID- 25993861
TI  - [Automatic classification method of star spectra data based on manifold fuzzy
      twin support vector machine].
AB  - Support vector machine (SVM) with good leaning ability and generalization is
      widely used in the star spectra data classification. But when the scale of data
      becomes larger, the shortages of SVM appear: the calculation amount is quite
      large and the classification speed is too slow. In order to solve the above
      problems, twin support vector machine (TWSVM) was proposed by Jayadeva. The
      advantage of TSVM is that the time cost is reduced to 1/4 of that of SVM. While
      all the methods mentioned above only focus on the global characteristics and
      neglect the local characteristics. In view of this, an automatic classification
      method of star spectra data based on manifold fuzzy twin support vector machine
      (MF-TSVM) is proposed in this paper. In MF-TSVM, manifold-based discriminant
      analysis (MDA) is used to obtain the global and local characteristics of the
      input data and the fuzzy membership is introduced to reduce the influences of
      noise and singular data on the classification results. Comparative experiments
      with current classification methods, such as C-SVM and KNN, on the SDSS star
      spectra datasets verify the effectiveness of the proposed method.

PMID- 25993862
TI  - [Study on a new method for instrumental line shape measurement of spatial
      heterodyne interference spectrometer].
AB  - Spatial heterodyne spectroscopy(SHS)is a novel method for hyper-spectral
      analysis, and instrument line shape function is one of the basic performance
      parameters, which should be precisely characterized. Based on the analysis of the
      influence factors(apodization, limited angle, abaxial detector element) and
      special requirement for measuring method and source, the present paper put
      forward a new method for measuring with tunable monochromatic light source, and
      designed experimental equipment with tunable laser and integrating sphere
      eliminating speckle. Selecting typical spectral range within band range for high
      spectral resolution scanning (0. 1nm step), the energy distribution of spectrum
      was obtained according to error correction, spectral reconstruction and
      normalization. In addition, rule curve for FWHM and wavelength was obtained by
      the full spectral range scanning interferogram. Finally, theoretical spectrum,
      ILS convolution simulated spectrum (LBL calculated), and measured carbon dioxide
      absorption spectrum by ground-based experiment are in good agreement. The result
      shows that the instrument line shape function exhibits high accuracy.

PMID- 25993863
TI  - [Study on single-walled carbon nanotube thin film photoelectric device].
AB  - The single-walled carbon nanotube film photoelectric device was invented, and it
      can generate net photocurrent under bias voltage when it is illuminated by the
      laser. The influences of bias voltage, laser power and illuminating position on
      the net photocurrent were investigated. The experimental results showed that when
      the center of the film was illuminated, the photocurrent increased with the
      applied bias, but tended to saturate as the laser power increased. As the voltage
      and the laser power reached 0. 2 V and 22. 7 mW respectively, the photocurrent
      reached 0. 24 uA. When the voltage was removed, the photocurrent varied with the
      laser illuminating position on the film and its value was distributed
      symmetrically about the center of the device. The photocurrent reached maximum
      and almost zero respectively when the laser illuminated on two ends and the
      center of the film. Analysis proposes that the net photocurrent can be generated
      due to internal photoelectric effect when the device is under voltage and the
      laser illuminates on the center of the film. It can be also generated due to
      photo-thermoelectric effect when the device is under no voltage and the laser
      illuminates on the film, and the relation between the net photocurrent and the
      illuminating position was derived according to the nature of thermoelectric power
      of single-walled carbon nanotubes with the established temperature model, which
      coincides with experimental result. Two effects are the reasons for the
      generation and variety of the net photocurrent and they superimpose to form the
      result of the net photocurrent when the device is under general conditions of
      voltage and laser illuminating position. The device has potential applications in
      the areas of photovoltaic device and optical sensor for its characteristic.

PMID- 25993864
TI  - [Multispectral image compression algorithms for color reproduction].
AB  - In order to improve multispectral images compression efficiency and further
      facilitate their storage and transmission for the application of color
      reproduction and so on, in which fields high color accuracy is desired, WF serial
      methods is proposed, and APWS_RA algorithm is designed. Then the WF_APWS_RA
      algorithm, which has advantages of low complexity, good illuminant stability and
      supporting consistent coior reproduction across devices, is presented. The
      conventional MSE based wavelet embedded coding principle is first studied. And
      then color perception distortion criterion and visual characteristic matrix W are
      proposed. Meanwhile, APWS_RA algorithm is formed by optimizing the. rate
      allocation strategy of APWS. Finally, combined above technologies, a new coding
      method named WF_APWS_RA is designed. Colorimetric error criterion is used in the
      algorithm and APWS_RA is applied on visual weighted multispectral image. In
      WF_APWS_RA, affinity propagation clustering is utilized to exploit spectral
      correlation of weighted image. Then two-dimensional wavelet transform is used to
      remove the spatial redundancy. Subsequently, error compensation mechanism and
      rate pre-allocation are combined to accomplish the embedded wavelet coding.
      Experimental results show that at the same bit rate, compared with classical
      coding algorithms, WF serial algorithms have better performance on color
      retention. APWS_RA preserves least spectral error and WF APWS_RA algorithm has
      obvious superiority on color accuracy.

PMID- 25993865
TI  - [Recent progress in nuclear magnetic resonance spectrum for drug research and
      development].
AB  - In the process of modern drug research, the new methods and technologies which
      can detect drug molecules' chemical composition, structure and interaction with
      biomolecules are always the key scientific problems people care about. Spectra
      (including IR, UV and NMR) are the most common analytical methods, of which NMR
      can obtain detailed parameter about the nucleus of organic molecules through
      researching the laws of nuclear transition in the impact of surrounding chemical
      environment. The parameter contains rich information about the chemical
      composition, structure and interaction with other molecules of organic molecules.
      In many complex environments, such as liquid, solid or gas state, even biological
      in situ environment, NMR can provide molecules' chemical composition, atomic
      resolution three-dimensional structure, information of interaction with each
      other and dynamic process, especially the information about drug interacting with
      biomacromolecules. In recent years, the applications of nuclear magnetic
      resonance spectrum in drug research and development are more and more widespread.
      This paper reviewed its recent progress in structure and dynamic of targeted
      biological macromolecules, drug design and screening and drug metabolism in drug
      research and development. In the first part, we gave a brief introduction of
      nuclear magnetic resonance technology and its applications in drug research. In
      the second part, we explained the basic principles briefly and summarized
      progress in methods and techniques for drug research. In the third part, we
      discussed applications of nuclear magnetic resonance ir structure and dynamic of
      targeted biological macromolecules, drug design and screening and drug metabolism
      in detail. The conclusions were stated in the last part.

PMID- 25993866
TI  - [Connective tissue dysplasia in patients with celiac desease as a problem of
      violation of adaptation reserve islands of the body].
AB  - Clinically significant dysplasia of connective tissue in patients with celiac
      disease is often responsible for various visceral disorders. Different
      disturbances of motor and evacuation functions are often determined in this
      patients (gastroesophageal reflux, duodenogastral reflux, spastic and
      hyperkinetic dyskinesia). The clinical course of the celiac disease, associated
      with connective tissue dysplasia, is characterized by asthenovegetative syndrome,
      reduced tolerance to physical activity, general weakness, fatigue and emotional
      instability. These data should be considered in choosing a treatment.

PMID- 25993867
TI  - [The role of the intestine microbiota in the development of obesity].
AB  - Medical societies all around the world have been alarmed by the problem of
      obesity and the diseases related to it. You can call it pandemic. Nowadays,
      obesity is viewed as a chronic condition that requires proper treatment. People
      suffering from it typically consume a larger amount of food, which in turn leads
      to changes in intestinal microbiome. Furthermore, obese people possess a specific
      kind of microflora, which might influence on the structure of human genome.
      Changes of intestine microflora depend on age, point of residence, culture
      specifics, lifestyle and socio-economic status. Currently, we can adjust
      intestinal micloflora by presenting pro- and prebiotics, which we believe might
      help in improving obesity level.

PMID- 25993868
TI  - [Gastroesophageal reflux disease in patients receiving chemotherapy: clinical,
      endoscopic, morphological and immunohistochemical features].
AB  - THE PURPOSE OF THE STUDY: Determine the pathogenetic significance of express
      molecules PCNA, Bcl-2, NF-Kb and tachykinins (substance P, neurokinin A) in
      patients with gastroesophageal reflux disease (GERD), receiving polychemotherapy
      (PCT). MATERIALS AND METHODS: In total 60 patients were examined with GERD time
      divided into 2 equal groups on the receiving PCT Leukemia over standard dose for
      at least one year. The first group consisted of 30 subjects with non-erosive GERD
      (NEGERD) endoscopically positive form receiving PCT. The second group consisted
      of 30 subjects with erosive form of GERD (EFGERD) receiving PCT. Patients
      underwent endoscopy, morphological and immunohistochemical examination of the
      esophageal mucosa to the definition expression of molecules PCNA, Bcl-2,
      neurokinin A, substance P and factor Nf-Kb. In patients with refractory form of
      GERD to proton pump inhibitors therapy (PPIs), additionally imposed
      ursodeoxycholic acid. THE RESULTS: Patients with NEGERD receiving PCT in 33.3% of
      cases formed refractory to PPIs form of the disease, when EFGERD refractoriness
      occurs in 46.7% of patients, which is associated with slowing the proliferation
      of epithelial cells of the esophagus due to decreased expression of PCNA. Reduced
      expression of neurokinin A in patients receiving PCT is associated with less
      activity and intensity of inflammation of esophageal mucosa. Against the
      background of a high degree of PCT expression of Bcl-2 and factor Nf-Kb, which
      may explain the frequent detection of atrophic and meta- plastic changes in the
      esophageal mucosa. Appointment of ursodeoxycholic acid in the complex therapy of
      GERD can overcome resistance to PPIs and improve the performance of cell renewal.
      CONCLUSION: Due to the frequent development of GERD refractory to PPIs in
      patients suffering from diseases requiring the appointment of long-term courses
      of PCT requires the appointment of cytoprotective therapy, as that can be used
      ursodeoxycholic acid.

PMID- 25993869
TI  - [Comorbidity of diseases of the liver, biliary tract and psoriasis].
AB  - MATERIALS AND METHODS: Groups of patients with various forms of psoriasis are
      investigated: with a widespread dermatosis in a progressing phase; group of
      comparison was consisted of patients with a local dermatosis. Clinical,
      biochemical, ultrasonic methods of research of a liver and a bilious ways,
      duodenal sounding are applied. RESULTS: Aberrations of functional tests of a
      liver, pathology of a biliarny path, violation of a lipidic exchange, laboratory
      and tool symptoms of fibrosis were reliable more often at patients with
      widespread psoriasis, than patients with a local form of a disease. CONCLUSION:
      The widespread form of psoriasis is associated with non alcoholic fatty disease
      of a liver and big frequency of diseases of bilious ways. Results of researches
      need to be considered when carrying out basic therapy of widespread psoriasis.

PMID- 25993870
TI  - [Irritable bowel syndrome with extraintestinal manifestations from a position of
      neuroendocrine pathology].
AB  - The aim of this study was to investigate the mechanism (s) of action of
      gastrointestinal hormones in the pathogenesis of irritable bowel syndrome (IBS),
      and the correlation between gastrointestinal hormones and psychological factors.
      Patients with IBS were divided into IBS with normal emotional state ratings and
      IBS in anxiety-depressive states groups. The two groups were then subdivided into
      IBS-constipation predominant (IBS-C) and IBS-diarrhea predominant (IBS-D) groups.
      Non-IBS patients with normal depression and anxiety ratings were recruited as
      controls. The expression of somatostatin (SS) and vasointestinalpeptid (VIP),
      motilin in the colonic mucosa was detected by immunohistochemistry and
      radioimmunoassay. The anxiety-depression scores of patients with IBS were
      significantly different from those of the control group. The expression levels of
      SS and VIP, motilin colonic mucosa of the patients with IBS were higher compared
      with those of the control.group. Furthermore, the expression level of SS in the
      IBS-C group demonstrated a significantly larger increase than that in the IBS-D
      group; however, there was no significant difference in the expression of VIP
      between the IBS-C and IBS-D groups. In addition, the expression levels of SS and
      VIP, motilin in the IBS groups with normal emotional state ratings were notably
      different from those in the IBS groups in anxiety-depressive states. Anxiety
      depressive states may lead to changes in the secretion of SS and VIP, motilin,
      and subsequently to changes in gastrointestinal motility and function.

PMID- 25993871
TI  - [New opportunities in the diagnosis of ulcerative colitis].
AB  - PURPOSE OF THE STUDY: to analyze the expression of markers of apoptosis and
      proliferation in patients with ulcerative colitis. MATERIALS AND METHODS: in 80
      patients with ulcerative colitis the analysis of expression of apoptosis marker
      BAX and proliferation marker Ki-67, as well as the cell cycle regulator p53 in
      biopsy materials of the mucous membrane of the colon was carried out. THE
      RESULTS: decreased cell proliferative activity and increase of the apoptosis rate
      depending on the severity, the localization of the inflammatory process and its
      endoscopic activity were registered.

PMID- 25993872
TI  - [Changes in markers of proliferation, neoangiogenesis and plasminogen activation
      system in rectal cancer tissue].
AB  - AIM OF THE STUDY: determination of levelsofsometissuegrowth factors,
      fibrinolyticsystemindicesand MMP-3 for specifi- cation of the role of their
      changes in moderately differentiated adenocarcinoma of the rectum. MATERIALS AND
      METHODS. Levels of growth factors and neoangiogenesis, tissue
      fibrinolyticsystemindicesand MMP-3were studiedin cytosols of tissue obtained from
      73 patients (primary adenocarcinomas, st. III, G2, 47 men and 26 women aged 38-74
      years, T1-3N0M0) by the ELISA method using standard test kits. RESULTS: Increase
      in the content of growth factors VEGF-A, IGF and TGF-beta1, the receptor protein
      VEGF-R, plasminogen activator uPA and metalloproteinases MMP-3 was detected
      inadenocarcinoma of the rectum. Gender differences inVEGF-Aand TGF-beta1 content
      were found. Increase in levels and activity of uPA and MMP-3 only was detected in
      perifocal zone of the tumor. Changes in EGF content were found neither in
      adenocarcinoma tissue nor in its perifocal zone. No significant gender
      differenceswere observed intissue fibrinolyticsystemandMMP-3. Age differenceswere
      not found either. CONCLUSION. I. Concurrent expressionof IGF-I, IGF-II, TGF-beta1
      and VEGF-Aanditsreceptorinmalignanttumortissue, as well as increasedplasmin
      release from proenzyme and MMP-3 activationis apparently associatedwith the
      formation ofpathogenic mechanism of vasculature development in moderately
      differentiated adenocarcinoma of the rectum. 2. Activation of uPA and MMP-3 in
      perifocal zone of the tumor can serve as an indexof its invasive activity. 3.
      Genderdifferencesin VEGF-A and TGF-beta1, content in tumor tissue were observed;
      significant association between natient gender and levels of IGF, EGF.
      fibinolvsis indices and MMP-3 was not found.

PMID- 25993873
TI  - [Regional peculiarities of the distribution of innate and adaptive immune cells
      in different segments of the intestine as factor determining the localization of
      the pathological process].
AB  - The intestine represents the largest compartment of the immune system. Gut
      associated lymphoid tissue (GALT) is a sensor region for luminal content and
      plays an important role in lymphoid maturation, activation and differentiation.
      We studied the regional peculiarities of the distribution of T-bet+ (Thl), GATA
      3+ (Th2), RORgammat+ (Th17), Foxp3+ (Treg) immunopositive lymphocytes and TLR2-,
      TLR4-, NOD- and RIG-like expression levels by lymphocytes of the gut-associated
      lymphoid tissue in the intestine of Wistar rats. The immunopositive lymphocytes
      were determined using an indirect immunofluorescence technique with using a
      monoclonal rat antibody. We have found regional differences distribution of
      immune cell populations along the length of the intestine.

PMID- 25993874
TI  - [Eosinophilic esophagitis diagnostic features].
AB  - Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by
      eosinophilic infiltration and inflammation of the gastrointestinal tract in the
      absence of other causes of tissue eosinophilia. The clinical course of EoE like
      gastroesophageal reflux disease with eosinophilic infiltration of the esophageal
      epithelium. EoE widely diagnosed abroad in children and adults, whereas in Russia
      the disease is almost never diagnosed. Upon detection of eosinophilia in the
      biopsy of the esophagus should exclude other causes. The correct clinical
      diagnosis in combination with the study of biopsy tissue of the esophagus and
      other laboratory methods (including allergic testing) is crucial in achieving the
      effectiveness of therapy EoE.

PMID- 25993875
TI  - [Eosinophilic esophagitis in adults: current approaches to diet therapy].
AB  - The review describes the basic strategy of eosinophilic esophagitis diet therapy
      in adult patients: elemental diet, allergy testing-directed food elimination diet
      and empirical elimination diet. The review includes information about the effects
      of different methods of diet therapy on the severity of eosinophilic infiltration
      of the esophageal mucosa and symptoms of eosinophilic esophagitis.

PMID- 25993876
TI  - [Hepatic haemangioma as sistemic manifestation of rheumatoid arthritis].
AB  - This article presents the clinical data regarding to the incidence of hepatic
      haemangioma in rheumatoid arthritis (RA) patients. Haemangioma of the liver has
      been diagnosed by ultrasonography dramatically oftener in RA than in OA: in 8
      from 37 RA pts and neither in 120 osteoarthritis pts. Hepatic haemangioma was
      associated with long standing erosive RA, extra-articular RA manifestations, high
      levels of rheumatoid factor and ACCP. Moreover in RA pts with hepatic haemangioma
      we revealed significantly raised levels of pro-inflammatory cytokines, which can
      impact on the angiogenesis in RA. Obtained clinical data may contribute in the
      understanding of liver vessels involvement in RA and pose the role of systemic
      connective tissue lesion and immune inflammation in this process.

PMID- 25993877
TI  - [Clinical case of the sharp cholecystitis process under mask of a sharp
      myocardial infarction].
AB  - Presented case report of an.elderl patient having polymorbidity pathology.
      Clinical "mask" of the destructive cholecystitisis an acut emyocardial infarction
      complicated bycardia casthma. The diagnosis of myocardial infarction has not been
      confirmed. Onemergency indications was performed cholecystectomy.

PMID- 25993878
TI  - [Mascs of functional disorders of the biliary tract].
AB  - The survey of its own and literature data describes the clinical "masks" of the
      primary and second functional disorders of the biliary tract, describes the
      mechanisms of their formation, which include the plural disturbances of the
      organs interactions, psycho - emotional and vegetative disturbances, development
      ofbiliar and pancreatic insufficiency. It is shown that Hymecromone (Odeston) can
      be successfully used, as the base means, with the treatment of patients with
      primary and second functional disorders of the biliary tract with different
      clinical "masks" of this pathology.

PMID- 25993879
TI  - [Conference publications: "Plenum NOGR conference in Saratov city"].

PMID- 25993880
TI  - [Nikolay Semashko the first Soviet People's Commissar of Health-- the founder of
      health care system of Obraztsov].

PMID- 25993881
TI  - Non-invasive diagnostic approach to non-alcoholic fatty liver disease: current
      evidence and future perspectives.
AB  - Non-alcoholic fatty liver disease is a new epidemic liver disease, thus, its
      early diagnosis and the identification of those patients with the worst prognosis
      is mandatory. Liver biopsy is still the diagnostic gold standard, even if it is
      associated to a significant rate of complications; moreover, the interpretation
      of histological samples is not always univocal. Several non-invasive alternative
      scores have been proposed for the diagnostic approach to non-alcoholic fatty
      liver disease. This article evaluates the performance of the currently available
      non-invasive diagnostic strategies. The authors also suggest a potential
      diagnostic algorithm, with two or more non-invasive techniques, to increase the
      overall accuracy for identifying patients with worst prognosis, and to minimize
      the recourse to liver biopsy. 

PMID- 25993882
TI  - Sweet Poisons: Honeys Contaminated with Glycosides of the Neurotoxin Tutin.
AB  - Poisonings due to consumption of honeys containing plant toxins have been
      reported widely. One cause is the neurotoxin tutin, an oxygenated sesquiterpene
      picrotoxane, traced back to honeybees (Apis mellifera) collecting honeydew
      produced by passionvine hoppers (Scolypopa australis) feeding on sap of the
      poisonous shrub tutu (Coriaria spp.). However, a pharmacokinetic study suggested
      that unidentified conjugates of tutin were also present in such honeys. We now
      report the discovery, using ion trap LC-MS, of two tutin glycosides and their
      purification and structure determination as 2-(beta-d-glucopyranosyl)tutin (4)
      and 2-[6'-(alpha-d-glucopyranosyl)-beta-d-glucopyranosyl]tutin (5). These
      compounds were used to develop a quantitative triple quadrupole LC-MS method for
      honey analysis, which showed the presence of tutin (3.6 +/- 0.1 MUg/g honey),
      hyenanchin (19.3 +/- 0.5), tutin glycoside (4) (4.9 +/- 0.4), and tutin
      diglycoside (5) (4.9 +/- 0.1) in one toxic honey. The ratios of 4 and 5 to tutin
      varied widely in other tutin-containing honeys. The glycosidation of tutin may
      represent detoxification by one or both of the insects involved in the food chain
      from plant to honey. 

PMID- 25993883
TI  - Strategic creatine supplementation and resistance training in healthy older
      adults.
AB  - Creatine supplementation in close proximity to resistance training may be an
      important strategy for increasing muscle mass and strength; however, it is
      unknown whether creatine supplementation before or after resistance training is
      more effective for aging adults. Using a double-blind, repeated measures design,
      older adults (50-71 years) were randomized to 1 of 3 groups: creatine before (CR
      B: n = 15; creatine (0.1 g/kg) immediately before resistance training and placebo
      (0.1 g/kg cornstarch maltodextrin) immediately after resistance training),
      creatine after (CR-A: n = 12; placebo immediately before resistance training and
      creatine immediately after resistance training), or placebo (PLA: n = 12; placebo
      immediately before and immediately after resistance training) for 32 weeks. Prior
      to and following the study, body composition (lean tissue, fat mass; dual-energy
      X-ray absorptiometry) and muscle strength (1-repetition maximum leg press and
      chest press) were assessed. There was an increase over time for lean tissue mass
      and muscle strength and a decrease in fat mass (p < 0.05). CR-A resulted in
      greater improvements in lean tissue mass (Delta 3.0 +/- 1.9 kg) compared with PLA
      (Delta 0.5 +/- 2.1 kg; p < 0.025). Creatine supplementation, independent of the
      timing of ingestion, increased muscle strength more than placebo (leg press: CR
      B, Delta 36.6 +/- 26.6 kg; CR-A, Delta 40.8 +/- 38.4 kg; PLA, Delta 5.6 +/- 35.1
      kg; chest press: CR-B, Delta 15.2 +/- 13.0 kg; CR-A, Delta 15.7 +/- 12.5 kg; PLA,
      Delta 1.9 +/- 14.7 kg; p < 0.025). Compared with resistance training alone,
      creatine supplementation improves muscle strength, with greater gains in lean
      tissue mass resulting from post-exercise creatine supplementation. 

PMID- 25993884
TI  - RNAi-based inhibition of infectious myonecrosis virus replication in Pacific
      white shrimp Litopenaeus vannamei.
AB  - Disease in Pacific white shrimp Litopenaeus vannamei caused by the infectious
      myonecrosis virus (IMNV) causes significant socioeconomic impacts in infection
      prone shrimp aquaculture regions. The use of synthetic dsRNA to activate an RNA
      interference (RNAi) response is being explored as a means of disease prophylaxis
      in farmed shrimp. Here, survival was tracked in L. vannamei injected with long
      synthetic dsRNAs targeted to IMNV open reading frame (ORF) 1a, ORF1b, and ORF2
      genome regions prior to injection challenge with IMNV, and real-time RT-PCR was
      used to track the progress of IMNV infection and mRNA expression levels of the
      host genes sid1, dicer2, and argonaute2. Injection of dsRNAs targeting the ORF1a
      and ORF1b genes but not the ORF2 gene strongly inhibited IMNV replication over a
      3 wk period following IMNV challenge, and resulted in 90 and 83% shrimp survival,
      respectively. Host gene mRNA expression data indicated that the Sid1 protein,
      which forms a transmembrane channel involved in cellular import/export of dsRNA,
      increased in abundance most significantly in shrimp groups that were most highly
      protected by virus-specific dsRNA injection. Subclinical IMNV infections present
      in the experimental L. vannamei used increased markedly in the 2 d between
      injection of any of the 4 virus-specific or non-specific dsRNAs tested and IMNV
      challenge. While handling and injection stress are implicated in increasing IMNV
      replication levels, the underlying molecular factors that may have been involved
      remain to be elucidated. 

PMID- 25993885
TI  - Real-time RT-PCR for detection, identification and absolute quantification of
      viral haemorrhagic septicaemia virus using different types of standards.
AB  - In the present study, 2 systems of real-time RT-PCR-one based on SYBR Green and
      the other on TaqMan-were designed to detect strains from any genotype of viral
      haemorrhagic septicaemia virus (VHSV), with high sensitivity and
      repeatability/reproducibility. In addition, the method was optimized for
      quantitative purposes (qRT-PCR), and standard curves with different types of
      reference templates were constructed and compared. Specificity was tested against
      26 isolates from 4 genotypes. The sensitivity of the procedures was first tested
      against cell culture isolation, obtaining a limit of detection (LD) of 100 TCID50
      ml-1 (100-fold below the LD using cell culture), at a threshold cycle value (Ct)
      of 36. Sensitivity was also evaluated using RNA from crude (LD = 1 fg; 160 genome
      copies) and purified virus (100 ag; 16 copies), plasmid DNA (2 copies) and RNA
      transcript (15 copies). No differences between both chemistries were observed in
      sensitivity and dynamic range. To evaluate repeatability and reproducibility, all
      experiments were performed in triplicate and on 3 different days, by workers with
      different levels of experience, obtaining Ct values with coefficients of
      variation always <5. This fact, together with the high efficiency and R2 values
      of the standard curves, encouraged us to analyse the reliability of the method
      for viral quantification. The results not only demonstrated that the procedure
      can be used for detection, identification and quantification of this virus, but
      also demonstrated a clear correlation between the regression lines obtained with
      different standards, which will help scientists to compare sensitivity results
      between different studies. 

PMID- 25993886
TI  - Isolation of a novel aquatic birnavirus from rainbow trout Oncorhynchus mykiss in
      Australia.
AB  - In November 2010, a rainbow trout (Oncorhynchus mykiss) hatchery in Victoria
      reported increased mortality rates in diploid and triploid female fingerlings.
      Live and moribund fish were submitted for laboratory investigation. All fish
      showed hyperpigmentation of the cranial half of the body. Histological lesions
      were seen in all areas of skin examined despite the localised nature of the gross
      lesions. There was irregular hyperplasia and spongiosis, alternating with areas
      of thinning and architectural disturbance. Occasionally, particularly in
      superficial layers of epithelium, cells showed large, eosinophilic inclusions
      that obscured other cellular detail. A small number of fish had necrosis in
      dermis, subcutis and superficial muscles. Bacteriological culture of skin and
      gills was negative for all bacterial pathogens, including Flavibacterium
      columnare, the agent of columnaris disease. Attempts at virus isolation from the
      skin of affected fish resulted in the development of a cytopathic effect in RTG-2
      cell cultures suggestive of the presence of a virus. Negative contrast electron
      microscopy of cell culture supernatant demonstrated the presence of viral
      particles with the typical morphology of birnaviruses. Preliminary molecular
      characterisation identified an aquabirnavirus that differed from both the
      Tasmanian aquabirnavirus (TABV) and other aquabirnaviruses exotic to Australia.
      Previous isolates of aquabirnaviruses in Australia and New Zealand have been from
      healthy fish in a marine environment. This is the first report of an
      aquabirnavirus isolated from young salmonids at a freshwater hatchery in
      Australia. The role of the virus in the mortality event on the farm is uncertain
      as no further deaths attributable to this virus have occurred in the 4 yr since
      its initial discovery. The virus has been provisionally named Victorian trout
      aquabirnavirus (VTAB). 

PMID- 25993887
TI  - Occurrence of antibiotic resistance genes in culturable bacteria isolated from
      Turkish trout farms and their local aquatic environment.
AB  - Antibiotic resistance and presence of the resistance genes were investigated in
      the bacteria isolated from water, sediment, and fish in trout farms. A total of 9
      bacterial species, particularly Escherichia coli, were isolated from the water
      and sediment samples, and 12 species were isolated from fish. The antimicrobial
      test indicated the highest resistance against sulfamethoxazole and ampicillin in
      coliform bacteria, and against sulfamethoxazole, imipenem, and aztreonam in known
      pathogenic bacteria isolated from fish. The most effective antibiotics were
      rifampicin, chloramphenicol, and tetracycline. The multiple antibiotic resistance
      index was above the critical limit for almost all of the bacteria isolated. The
      most common antibiotic resistance gene was ampC, followed by tetA, sul2, blaCTX
      M1, and blaTEM in the coliform bacteria. At least one resistance gene was found
      in 70.8% of the bacteria, and 66.6% of the bacteria had 2 or more resistance
      genes. Approximately 36.54% of the bacteria that contain plasmids were able to
      transfer them to other bacteria. The plasmid-mediated transferable resistance
      genes were ampC, blaCTX-M1, tetA, sul2, and blaTEM. These results indicate that
      the aquatic environment could play an important role in the development of
      antibiotic resistance and the dissemination of resistance genes among bacteria. 

PMID- 25993888
TI  - Proliferative kidney disease in brown trout: infection level, pathology and
      mortality under field conditions.
AB  - Proliferative kidney disease (PKD) is an emerging disease threatening wild
      salmonid populations. In temperature-controlled aquaria, PKD can cause mortality
      rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality
      in wild brown trout Salmo trutta fario are available. The aim of this study was
      to investigate mortality rates and pathology in brown trout kept in a cage within
      a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of
      the-year (YOY) brown trout, free of T. bryosalmonae, were exposed in the River
      Wutach, in the northeast of Switzerland, during 3 summer months. Samples of wild
      brown trout caught by electrofishing near the cage location were examined in
      parallel. The incidence of PKD in cage-exposed animals (69%) was not
      significantly different to the disease prevalence of wild fish (82 and 80% in the
      upstream and downstream locations, respectively). The mortality in cage-exposed
      animals, however, was as low as 15%. At the termination of the exposure
      experiment, surviving fish showed histological lesions typical for PKD
      regression, suggesting that many YOY brown trout survive the initial infection.
      Our results at the River Wutach suggest that PKD in brown trout does not always
      result in high mortality under natural conditions. 

PMID- 25993889
TI  - Denman Island disease in Washington State, USA: distribution and prevalence in
      Pacific and Olympia oysters.
AB  - We sampled over 2400 wild, feral, and cultured Pacific oysters Crassostrea gigas
      and Olympia oysters Ostrea lurida in Washington State, USA, from 2002 to 2006 to
      estimate the prevalence of infection with Mikrocytos mackini, the causative agent
      of Denman Island disease. Both histology and qualitative PCR methods were used.
      Estimates of true prevalence of M. mackini infection in C. gigas, after
      accounting for imperfect test sensitivity, ranged from mean values of 0 to 10.0%
      by histology and 0 to 8.4% based on pooled PCR samples. M. mackini was not
      detected in any of the O. lurida samples. Results suggest a lower prevalence of
      the pathogen and severity of this oyster disease in Washington than that
      indicated in previous reports from British Columbia, Canada, potentially
      attributable to higher seawater temperatures in the Washington sample locations. 

PMID- 25993890
TI  - Whirling disease revisited: pathogenesis, parasite biology and disease
      intervention.
AB  - Whirling disease (WD) is an ecologically and economically debilitating disease of
      rainbow trout Oncorhynchus mykiss caused by the actinosporean spores of the
      parasite Myxobolus cerebralis. M. cerebralis has a complex, 2-host life cycle
      alternating between salmonid fish and the oligochaete host Tubifex tubifex. The
      parasite alternates between 2 spore forms as transmission stages: an
      actinosporean triactinomyxon spore that is produced in the oligochaete host and a
      myxosporean spore that develops in the salmonid host. Waterborne triactinomyxon
      spores released from infected T. tubifex oligochaetes attach to the salmonid host
      by polar filament extrusion elicited by chemical (nucleoside) and mechanical
      (thigmotropy) stimuli-a process which is rapidly followed by active penetration
      of the sporoplasms into the fish epidermis. Upon penetration, sporoplasms
      multiply and migrate via peripheral nerves and the central nervous system to
      reach the cartilage where they form trophozoites which undergo further
      multiplication and subsequent sporogenesis. M. cerebralis myxospores are released
      into the aquatic environment when infected fish die and autolyse, or when they
      are consumed and excreted by predators. Myxospores released into the water are
      ingested by susceptible T. tubifex where they develop intercellularly in the
      intestine over a period of 3 mo through 4 developmental stages to give rise to
      mature actinospores. In this article, we review our current understanding of WD
      the parasite and its alternate hosts, life cycle and development of the parasite
      in either host, disease distribution, susceptibility and resistance mechanisms in
      salmonid host and strategies involved in diagnosis, prevention and control of WD.

PMID- 25993892
TI  - Improvement in primary school adherence to the NSW Healthy School Canteen
      Strategy in 2007 and 2010.
AB  - ISSUE ADDRESSED: Since 2005, a government-endorsed strategy guiding food sold in
      New South Wales school canteens has been in place. This study describes the
      changes in school canteen food between 2007 and 2010 and characterises schools
      most likely to adhere to strategy guidelines. METHODS: Menus obtained from a
      cohort of primary and central schools in the Hunter New England region of New
      South Wales were audited using a traffic light system of classification. Energy
      dense, nutrient-poor or 'red' items are restricted; 'amber' are to be selected
      carefully and healthier 'green' items are encouraged. RESULTS: In 2007, 7% of
      schools had no red items on their menu. In 2010, this improved to 22% (P < 0.05).
      In 2010, small schools (OR = 1.9, 95% CI = 1.25-3.05, P = 0.003); lower
      socioeconomic schools (OR = 1.3, 95% CI = 1.02-1.78, P = 0.03); non-government
      (OR = 1.7, 95% CI = 1.22-2.23, P = 0.001) and rural schools (OR = 1.7, 95% Cl =
      1.30-2.25, P < 0.001) had higher odds of having red items on the menu. No
      significant change occurred in the proportion of green foods listed for sale
      between 2007 and 2010. CONCLUSIONS: Proportion of schools adhering to strategy
      guidelines had increased slightly, however, most continue to list red items for
      regular sale. SO WHAT? For health policies to improve public health they need
      implementation. Findings suggest more work is required, particularly in small
      schools, rural schools and non-government schools.

PMID- 25993893
TI  - Modelling non-steady-state isotope enrichment of leaf water in a gas-exchange
      cuvette environment.
AB  - The combined use of a gas-exchange system and laser-based isotope measurement is
      a tool of growing interest in plant ecophysiological studies, owing to its
      relevance for assessing isotopic variability in leaf water and/or transpiration
      under non-steady-state (NSS) conditions. However, the current Farquhar & Cernusak
      (F&C) NSS leaf water model, originally developed for open-field scenarios, is
      unsuited for use in a gas-exchange cuvette environment where isotope composition
      of water vapour (deltav ) is intrinsically linked to that of transpiration
      (deltaE ). Here, we modified the F&C model to make it directly compatible with
      the deltav -deltaE dynamic characteristic of a typical cuvette setting. The
      resultant new model suggests a role of 'net-flux' (rather than 'gross-flux' as
      suggested by the original F&C model)-based leaf water turnover rate in
      controlling the time constant (tau) for the approach to steady sate. The validity
      of the new model was subsequently confirmed in a cuvette experiment involving
      cotton leaves, for which we demonstrated close agreement between tau values
      predicted from the model and those measured from NSS variations in isotope
      enrichment of transpiration. Hence, we recommend that our new model be
      incorporated into future isotope studies involving a cuvette condition where the
      transpiration flux directly influences deltav . There is an increasing popularity
      among plant ecophysiologists to use a gas-exchange system coupled to laser-based
      isotope measurement for investigating non-steady state (NSS) isotopic variability
      in leaf water (and/or transpiration); however, the current Farquhar & Cernusak
      (F&C) NSS leaf water model is unsuited for use in a gas-exchange cuvette
      environment due to its implicit assumption of isotope composition of water vapor
      (deltav ) being constant and independent of that of transpiration (deltaE ). In
      the present study, we modified the F&C model to make it compatible with the
      dynamic relationship between deltav and deltaE as is typically associated with a
      cuvette setting. Using an experiment conducted on cotton leaves, we show that the
      modified NSS model performed well in predicting the time constant for the
      exponential approach of leaf water toward steady state under cuvette conditions.
      Such a result demonstrates the applicability of this new model to gas-exchange
      cuvette conditions where the transpiration flux directly influences deltav , and
      therefore suggests the need to incorporate this model into future isotope studies
      that employ a laser-cuvette coupled system. 

PMID- 25993894
TI  - Inter-participant variability in daily physical activity and sedentary time among
      male youth sport footballers: independent associations with indicators of
      adiposity and cardiorespiratory fitness.
AB  - Participation in youth sport is assumed to promote and contribute towards more
      physically active lifestyles among children and adolescents. The aim of this
      study was to examine inter-participant variability in objectively measured
      habitual physical activity (PA) behaviours and sedentary time among youth sport
      participants and their implications for health. One-hundred-and-eighteen male
      youth sport footballers (Mean +/- s = 11.72 +/- 1.60) wore a GT3X accelerometer
      for 7 days. Average daily PA [min . day(-1), in light (LPA), moderate (MPA),
      vigorous (VPA) and combined moderate-to-vigorous (MVPA)] and sedentary time were
      calculated. Participants' body mass index adjusted for age and sex (BMI-standard
      deviation score), per cent body fat (BF%), waist circumference and
      cardiorespiratory fitness were assessed. Results revealed that variability in
      daily PA behaviours and sedentary time (min . day(-1)) was associated with BMI
      standard deviation score [VPA (-), MVPA (-)], BF% [sedentary time (+), VPA (-),
      MVPA (-)], waist circumference [sedentary time (+), LPA (-)] and
      cardiorespiratory fitness [sedentary time (-), MPA (+), VPA (+), MVPA (+)].
      Whilst sedentary time and MVPA were not related to health outcomes independent of
      one another, associations with markers of adiposity and cardiorespiratory fitness
      were stronger for sedentary time. Sedentary time was also significantly
      positively related to waist circumference independent of VPA. Results demonstrate
      inter-participant variability in habitual PA and sedentary time among youth sport
      participants which holds implications for their health. Thus, promoting PA and,
      in particular, reducing sedentary time may contribute towards the prevention of
      adverse health consequences associated with a physically inactive lifestyle for
      children and adolescents active in the youth sport context. 

PMID- 25993895
TI  - Calcium oxalate calculi-induced clusterin expression in kidney.
AB  - The aim of the study was to investigate clusterin expression in the kidney and
      evaluate the urine clusterin level in the kidney stone formers. (1) In vitro, we
      treated the Madin-Darby canine kidney (MDCK) cell line with different
      concentrations of calcium oxalate (CaOx), and then the clusterin protein
      expression in the cells was evaluated by Western blotting. (2) Kidney stone
      patients who received percutaneous nephrolithotomy were enrolled in our study.
      Urine samples were collected before surgery, the kidney punctured to obtain
      kidney tissue guided by ultrasound intraoperatively. Clusterin expression in the
      human kidney tissue was evaluated by immunochemistry. The urine clusterin level
      was determined by enzyme-linked immunosorbent assay. Non-kidney disease subjects
      were chosen as controls. In vitro, the clusterin expression was up-regulated in
      the MDCK cells induced by CaOx. The study included 49 patients and 41 non-kidney
      disease subjects. All calculi were composed of calcium oxalate monohydrate or
      calcium oxalate dihydrate and a few also contained protein or uric acid. Mean +/-
      SD urine clusterin level was 17.47 +/- 18.61 MUg/ml in patients, and 3.31 +/-
      5.42 MUg/ml in non-kidney disease subjects, respectively (p < 0.001).
      Immunohistochemistry revealed the clusterin was located in the cytoplasm of the
      renal distal and collecting tubular epithelial cells. Also the tissue clusterin
      expression increased significantly in the kidney stone formers compared to the
      control groups (p = 0.001). CaOx could induce clusterin expression in renal
      tubular cells, and increase clusterin levels in the kidney and urine from the
      kidney stone formers.

PMID- 25993898
TI  - Capturing Cancer: Emerging Microfluidic Technologies for the Capture and
      Characterization of Circulating Tumor Cells.
AB  - Circulating tumor cells (CTCs) escape from primary or metastatic lesions and
      enter into circulation, carrying significant information of cancer progression
      and metastasis. Capture of CTCs from the bloodstream and the characterization of
      these cells hold great significance for the detection, characterization, and
      monitoring of cancer. Despite the urgent need from clinics, it remains a major
      challenge to capture and retain these rare cells from human blood with high
      specificity and yield. Recent exciting advances in micro/nanotechnology,
      microfluidics, and materials science have enable versatile, robust, and efficient
      cell isolation and processing through the development of new micro/nanoengineered
      devices and biomaterials. This review provides a summary of recent progress along
      this direction, with a focus on emerging methods for CTC capture and processing,
      and their application in cancer research. Furthermore, classical as well as
      emerging cellular characterization methods are reviewed to reveal the role of
      CTCs in cancer progression and metastasis, and hypotheses are proposed in regard
      to the potential emerging research directions most desired in CTC-related cancer
      research. 

PMID- 25993896
TI  - Dynamic evolution of resistance gene analogs in the orthologous genomic regions
      of powdery mildew resistance gene MlIW170 in Triticum dicoccoides and Aegilops
      tauschii.
AB  - KEY MESSAGE: Rapid evolution of powdery mildew resistance gene MlIW170
      orthologous genomic regions in wheat subgenomes. Wheat is one of the most
      important staple grain crops in the world and also an excellent model for plant
      ploidy evolution research with different ploidy levels from diploid to hexaploid.
      Powdery mildew disease caused by Blumeria graminis f.sp. tritici can result in
      significant loss in both grain yield and quality in wheat. In this study, the
      wheat powdery mildew resistance gene MlIW170 locus located at the Triticum
      dicoccoides chromosome 2B short arm was further characterized by constructing and
      sequencing a BAC-based physical map contig covering a 0.3 cM genetic distance
      region (880 kb) and developing additional markers to delineate the resistance
      gene within a 0.16 cM genetic interval (372 kb). Comparative analyses of the T.
      dicoccoides 2BS region with the orthologous Aegilops tauschii 2DS region showed
      great gene colinearity, including the structure organization of both types of
      RGA1/2-like and RPS2-like resistance genes. Comparative analyses with the
      orthologous regions from Brachypodium and rice genomes revealed considerable
      dynamic evolutionary changes that have re-shaped this MlIW170 region in the wheat
      genome, resulting in a high number of non-syntenic genes including resistance
      related genes. This result might reflect the rapid evolution in R-gene regions.
      Phylogenetic analysis on these resistance-related gene sequences indicated the
      duplication of these genes in the MlIW170 region, occurred before the separation
      of the wheat B and D genomes.

PMID- 25993897
TI  - Prospects of breeding high-quality rice using post-genomic tools.
AB  - KEY MESSAGE: The holistic understanding derived from integrating grain quality
      and sensory research outcomes in breeding high-quality rice in the light of post
      genomics resources has been synthesized. Acceptance of new rice genotypes by
      producers and consumers hinges not only on their potential for higher yield but
      recent emphasis has also been on premium-value genotypes that have the ability to
      satisfy consumer preferences for grain quality. This review article provides
      insights into how to link grain quality attributes and sensory perception to
      support breeding superior rice varieties. Recent advances in quality profiling
      and omics technologies have provided efficient approaches to identify the key
      genes and biochemical markers involved in rice quality traits. Emphasis has been
      given to the upcoming area of holistic understanding of grain quality and
      attributes derived from sensory evaluation to leverage integrative gene discovery
      strategies that enable breeding programs to efficiently tap the huge genetic
      diversity in rice for novel genes that enhance rice food quality.

PMID- 25993901
TI  - Homotopic reciprocal functional connectivity between anterior human insulae.
AB  - The aim of this study was to investigate functional connectivity between right
      and left insulae in the human brain. We studied a patient with implanted depth
      electrodes for epilepsy surgery evaluation with stereotactically placed symmetric
      depth electrodes in both insulae. Bipolar 1 Hz electrical stimulation of the
      right and left posterior short gyri in the anterior insula evoked responses in
      the contralateral insular structures. These responses showed a latency of 8-24
      ms. This report demonstrates for the first time bi-directional homotopic and
      heterotopic functional connectivity between right and left anterior insulae. The
      short latency of the evoked responses suggests mono- or oligo-synaptic
      connections, most likely via the corpus callosum.

PMID- 25993899
TI  - The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth
      Disease Epidemic patterns in Guangdong, China.
AB  - Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two
      major causative pathogens in hand, foot and mouth disease (HFMD) epidemics.
      However, CVA6, previously largely ignored, became the predominant pathogen in
      China in 2013. In this study, we describe the epidemiological trends of CVA6
      during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study
      results show that CVA6 has been one of three major causative agents of HFMD
      epidemics since 2009. The periodic rotation and dominance of the three pathogens,
      EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD
      epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major
      circulating CVA6 strains collected from 2009 to 2013 are distinct from the
      earlier strains collected before 2009. In conclusion, the discovery from this
      research investigating epidemiological trends of CVA6 from 2008 to 2013 explains
      the possible pattern of the continuous HFMD epidemic in China. The etiological
      change pattern also highlights the need for improvement for pathogen surveillance
      and vaccine strategies for HFMD control in China.

PMID- 25993900
TI  - Deep sparse multi-task learning for feature selection in Alzheimer's disease
      diagnosis.
AB  - Recently, neuroimaging-based Alzheimer's disease (AD) or mild cognitive
      impairment (MCI) diagnosis has attracted researchers in the field, due to the
      increasing prevalence of the diseases. Unfortunately, the unfavorable high
      dimensional nature of neuroimaging data, but a limited small number of samples
      available, makes it challenging to build a robust computer-aided diagnosis
      system. Machine learning techniques have been considered as a useful tool in this
      respect and, among various methods, sparse regression has shown its validity in
      the literature. However, to our best knowledge, the existing sparse regression
      methods mostly try to select features based on the optimal regression
      coefficients in one step. We argue that since the training feature vectors are
      composed of both informative and uninformative or less informative features, the
      resulting optimal regression coefficients are inevidently affected by the
      uninformative or less informative features. To this end, we first propose a novel
      deep architecture to recursively discard uninformative features by performing
      sparse multi-task learning in a hierarchical fashion. We further hypothesize that
      the optimal regression coefficients reflect the relative importance of features
      in representing the target response variables. In this regard, we use the optimal
      regression coefficients learned in one hierarchy as feature weighting factors in
      the following hierarchy, and formulate a weighted sparse multi-task learning
      method. Lastly, we also take into account the distributional characteristics of
      samples per class and use clustering-induced subclass label vectors as target
      response values in our sparse regression model. In our experiments on the ADNI
      cohort, we performed both binary and multi-class classification tasks in AD/MCI
      diagnosis and showed the superiority of the proposed method by comparing with the
      state-of-the-art methods.

PMID- 25993902
TI  - Transport of Low-Density Lipoprotein Into the Blood Vessel Wall During
      Atherogenic Diet in the Isolated Rabbit Carotid Artery.
AB  - BACKGROUND: Atherosclerosis is a chronic fibroproliferative disease that includes
      accumulation of cholesterol-rich lipids in the arterial wall. Though numerous
      studies have investigated atherosclerosis, not enough is known about the exact
      mechanisms of low-density lipoprotein (LDL) transport into the blood vessel wall.
      Therefore, we explored the (125)I-LDL transport into the arterial wall under
      constant perfusion flow and pressure as well as the influence of duration of
      atherogenic diet on (125)I-LDL transport and biomechanical properties of carotid
      artery. METHODS AND RESULTS: The isolated segment of rabbit carotid artery was
      used under constant perfusion flow and pressure-induced (0 mmHg and 140 mmHg)
      blood vessel distension, with the possibility to change and precisely calculate
      shear stress during the experiment. Obtained results indicate the influence of
      atherogenic diet duration and consequent variation of shear stress on (125)I-LDL
      transport into the blood vessel wall. (125)I-LDL transport into the blood vessel
      wall at low pressure-induced blood vessel distension decreases by the increase of
      the shear stress and in relation to the atherogenic diet duration. At high
      pressure-induced blood vessel distension, (125)I-LDL transport increases in
      relation to the atherogenic diet duration and the increase of shear stress.
      CONCLUSIONS: The influence of shear stress is a more dominant parameter on LDL
      uptake at low pressure-induced blood vessel distension; however, the atherogenic
      diet duration has more of a dominant influence on LDL uptake at high pressure
      induced vessel distension.

PMID- 25993903
TI  - Influence of Left Ventricular Stiffness on Hemodynamics in Patients With
      Untreated Atrial Septal Defects.
AB  - BACKGROUND: Although left ventricular (LV) stiffening with age is believed to
      increase left-to-right shunting in patients with atrial septal defects (ASD),
      clinical data have not confirmed this. We sought determinants of the pulmonary-to
      systemic flow ratio (Qp/Qs) in patients with untreated ASD. METHODS AND RESULTS:
      We retrospectively studied 180 patients with ASD who underwent percutaneous ASD
      closure between 2007 and 2011. Qp/Qs and LV stiffness were measured before ASD
      closure.The median age of the subjects was 18 years, and 117 (65.0%) were female.
      The mean ASD size adjusted for square root of body surface area (BSA) was 14.4+/
      4.2 mm/m, and the Qp/Qs was 2.28+/-0.74. Adjusted ASD size most strongly related
      to Qp/Qs (r=0.74, P<0.0001). Multivariate analysis revealed that LV stiffness was
      a significant predictor of Qp/Qs, independently of adjusted ASD size and vascular
      resistance (P=0.0015). Based on the multivariate model that accounts for the
      effects of LV stiffness and vascular resistance, the minimal adjusted diameter
      that can cause a Qp/Qs of 2.0 was predicted to be 7.3 mm/m. CONCLUSIONS: Qp/Qs in
      ASD can change significantly depending on LV stiffness, suggesting that it would
      increase with age. An ASD >7.3 mm/m in diameter has the potential to cause
      significant left-to-right shunting, and may require closure regardless of
      hemodynamic status at the time of assessment.

PMID- 25993904
TI  - Novel Compression Tool to Prevent Hematomas and Skin Erosions After Device
      Implantation.
AB  - BACKGROUND: The incidence of hematoma formation following implantation of a
      cardiovascular implantable electronic device (CIED) is estimated to be 5% even if
      a pressure dressing is applied. It is unclear whether a pressure dressing can
      really compress the pocket in different positions. Furthermore, the adhesive tape
      for fixing pressure dressings can tear the skin. We developed a new compression
      tool for preventing hematomas and skin erosions. METHODS AND RESULTS: We divided
      46 consecutive patients receiving anticoagulation therapy who underwent CIED
      implantation into 2 groups (Group I: conventional pressure dressing, Group II:
      new compression tool). The pressure on the pocket was measured in both the supine
      and standing positions. The incidence of hematomas was compared between the 2
      groups. The pressure differed between the supine and standing positions in Group
      I, but not in Group II (Group I: 14.8+/-7.1 mmHg vs. 11.3+/-9.9 mmHg, P=0.013;
      Group II: 13.5+/-2.8 mmHg vs. 13.5+/-3.5 mmHg, P=0.99). The incidence of
      hematomas and skin erosions was documented in 2 (8.7%) and 3 (13%) Group I
      patients, respectively. No complications were documented in Group II.
      CONCLUSIONS: The new compression tool can provide adequate continuous pressure on
      the pocket, regardless of body position. This device may reduce the incidence of
      hematomas and skin erosions after CIED implantation.

PMID- 25993905
TI  - Erratum: Distinct metabolomic signatures are associated with longevity in humans.

PMID- 25993906
TI  - The ventilatory response to muscle afferent activation during concurrent
      hypercapnia in humans: central and peripheral mechanisms.
AB  - NEW FINDINGS: What is the central question of this study? During hypercapnia but
      not normocapnia, activation of muscle afferents by postexercise circulatory
      occlusion increases ventilation, possibly due to additional activation of
      metabolite-stimulated muscle afferents. Alternatively, chemoreflex activation
      caused by hypercapnia may have a synergistic interaction with muscle afferent
      feedback, so stimulating breathing. What is the main finding and its importance?
      Muscle afferent activation during muscle hypercapnia with concurrent systemic
      normocapnia did not increase breathing. With systemic hypercapnia, there was a
      response that did not change with hyperoxic hypercapnia. A synergistic
      interaction between central chemoreception and muscle afferent feedback is
      therefore indicated. During hypercapnia, activation of thin-fibre muscle
      afferents using postexercise circulatory occlusion (PECO) provokes a ventilatory
      response not seen in normocapnia. We investigated the ventilatory responses to
      PECO when hypercapnia was restricted to the active muscle ('Local' trial) or
      during systemic hypercapnia ('Systemic' trial). In the Local trial, a hypercapnic
      gas mixture (5% CO2 in air) was inhaled for 5 min when circulation to the active
      calf muscle was open, then rapidly closed by thigh-cuff inflation (200 mmHg),
      immediately before a return to breathing room air and performance of isometric
      exercise and PECO. In the Systemic trial, circulation through the muscle was
      closed throughout the exercise and PECO phases, performed during the hypercapnic
      gas inhalation. In a third trial, in Systemic conditions a hyperoxic hypercapnic
      gas mixture (95% O2 and 5% CO2 ) was breathed for 1 min during PECO ('Hyperoxia'
      trial). The increase in ventilation during calf muscle exercise was not different
      between trials. In the Local trial, ventilation fell to pre-exercise levels
      during PECO, but in the Systemic trial it remained at end-exercise levels (4.9 +/
      0.8 l min(-1) ) and was equally well maintained throughout the Hyperoxia trial
      (4.3 +/- 1 l min(-1) ). Cardiovascular responses during PECO were not different
      in the three trials, indicating similar activation of muscle afferents. Sustained
      elevation of ventilation during PECO in the Systemic but not the Local trial
      suggests that ventilation is stimulated via an interaction between muscle
      afferent feedback and hypercapnia-induced chemoreceptor activation. The similar
      ventilatory responses in Systemic and Hyperoxia conditions further suggest that
      in this respect, central rather than peripheral chemoreceptors play the major
      role.

PMID- 25993908
TI  - Metformin reduces hyper-reactivity of platelets from patients with polycystic
      ovary syndrome by improving mitochondrial integrity.
AB  - Polycystic ovary syndrome (PCOS) is associated with decreased fertility, insulin
      resistance and an increased risk of developing cardiovascular disease. Treating
      PCOS patients with metformin improves fertility and decreases cardiovascular
      complications. Given that platelet activation contributes to both infertility and
      cardiovascular disease development, we assessed platelet reactivity in PCOS
      patients and the consequences of metformin treatment. Compared to washed
      platelets from healthy donors, platelets from PCOS patients demonstrated enhanced
      reactivity and impaired activation of the AMP-activated kinase (AMPK). PCOS
      platelets also demonstrated enhanced expression of mitochondrial proteins such as
      the cytochrome c reductase, ATP synthase and the voltage-dependent anion channel
      1. However, mitochondrial function was impaired as demonstrated by a decreased
      respiration rate. In parallel, the phosphorylation of dynamin-related protein-1
      (Drp-1) on Ser616 was increased while that on Ser637 decreased. The latter
      changes were accompanied by decreased mitochondrial size. In insulin-resistant
      PCOS patients (HOMA-IR> 2) metformin treatment (1.7 g per day for 4 weeks to 6
      months) improved insulin sensitivity, restored mitochondrial integrity and
      function and normalised platelet aggregation. Treatment was without effect in
      PCOS patients with HOMA-IR< 2. Moreover, treatment of megakaryocytes with
      metformin enhanced mitochondrial content and in the same cells metformin enhanced
      the phosphorylation of the Drp-1 on Ser637 via an AMPKalpha1-dependent mechanism.
      In conclusion, the improvement of mitochondrial integrity and platelet reactivity
      may contribute to the beneficial effects of metformin on cardiovascular disease. 

PMID- 25993907
TI  - What overweight women want from a weight loss app: a qualitative study on arabic
      women.
AB  - BACKGROUND: Overweight and obesity are international public health issues. With
      mobile and app use growing globally, the development of weight loss apps are
      increasing along with evidence that interventions using technology have been
      effective in the treatment of obesity. Although studies have been conducted
      regarding what content health professionals would recommend within weight loss
      apps, there are limited studies that explore users' viewpoints. There is
      specifically a paucity of research that takes the cultural background of the user
      into consideration, especially in Middle Eastern countries where the lives and
      weight loss intervention needs of women not only vary vastly from the West, but
      the obesity rate is also increasing exponentially. OBJECTIVE: The current study
      sought to explore the proposed features of an Arabic weight loss app by seeking
      the experiences and opinions of overweight and obese Saudi Arabian users in order
      to design a mobile phone app to fit their needs. METHODS: Focus group discussions
      were conducted with a purposive sample of volunteer overweight and obese Saudi
      women (BMI >= 25) who were older than 18 years and who owned a mobile phone. The
      most common Arabic and English weight loss mobile apps were downloaded to
      initiate dialogue about app usage and to get their opinions on what an ideal
      weight loss app would look like and the features it would include. All
      transcribed, translated discussions were thematically analyzed, categorized for
      each of the main topics of the discussion, and specific quotations were
      identified. RESULTS: Four focus groups were conducted with a total of 39
      participants. Most participants owned an Android mobile phone and only a few
      participants were aware of the availability of health-related apps. Barriers to
      weight loss were identified including: motivation, support (social and
      professional), boring diets, customs, and lifestyle. Diverse themes emerged as
      suggestions for an ideal weight loss app including: Arabic language and
      culturally sensitive; motivational support and social networking; dietary and
      physical activity tools; and a tailorable, user-friendly interface. CONCLUSIONS:
      This study identifies weight loss app features from the users' perspective, which
      should be considered in the development of a weight loss app for this population.

PMID- 25993909
TI  - Are currently GFR estimating equations and standard Kt/V value adequate for
      advanced chronic kidney disease (CKD) frail elderly patients?
AB  - Chronic kidney disease (CKD) elderly patients have a reduced glomerular
      filtration rate (GFR) due to the combination of ageing and chronic nephropathy
      damage. This situation is very important to be taken into account in order to
      prescribe an adequate medication and dialysis dose in this aged group. Besides,
      cognitive and urinary incontinence problems make difficult to obtain an adequate
      24-h urine collection in order to evaluate creatinine clearance in this group.
      Thus, a reliable GFR estimating equation would be very useful for assisting
      elderly CKD patients. Additionally, Kt/V is the main parameter currently used for
      dosing dialysis in stage V CKD young and elderly patients. However, frailty and
      sarcopenia are prevalent disorders usually suffered by old people, who also
      present many physiological changes that could make GFR estimating equations and
      standard Kt/V value to become unreliable in this particular group. In conclusion,
      based on all these facts, it seems crucial for clinical geriatric nephrology to
      carefully evaluate how reliable current GFR estimating equations are, as well as
      which would be an adequate Kt/V value in CKD frail elderly patients. 

PMID- 25993910
TI  - Reirradiation for second primary or recurrent cancers of the head and neck:
      Dosimetric and outcome analysis.
AB  - BACKGROUND: The purpose of this study was to examine outcomes, toxicity, and
      dosimetric characteristics of patients treated with reirradiation for head and
      neck cancers. METHODS: Fifty patients underwent >=2 courses of radiation therapy
      (RT) postoperatively or definitively with or without chemotherapy. Composite dose
      volume histograms (DVHs) for selected anatomic structures were correlated with
      grade >=3 late toxicity. RESULTS: Median initial and retreatment radiation dose
      was 64 and 60 Gy, respectively. Median overall survival (OS), progression-free
      survival (PFS), and 1-year PFS rates were 18 months, 11 months, and 45%,
      respectively, with 13 months median follow-up. Thirty-four percent of patients
      experienced grade >=3 late toxicity with 1 death from carotid blowout. The DVH
      corresponding to the carotid blowout fell above the third quartile compared with
      other patients. CONCLUSION: Our analysis is the first to systematically evaluate
      the dose to the carotid artery using composite dosimetry in head and neck
      reirradiation patients, and demonstrates a promising technique for evaluating the
      dose to other normal tissue structures. (c) 2015 Wiley Periodicals, Inc. Head
      Neck 38: E961-E969, 2016.

PMID- 25993911
TI  - In reference to systematic review and meta-analysis of Meniett therapy for
      Meniere's disease.

PMID- 25993912
TI  - Saccadic movement deficiencies in adults with ADHD tendencies.
AB  - The goal of the present study was to explore deficits in gaze detection and
      emotional value judgment during a saccadic eye movement task in adults with
      attention deficit/hyperactivity disorder (ADHD) tendencies. Thirty-two
      participants, consisting of 16 ADHD tendencies and 16 controls, were recruited
      from a pool of 243 university students. Among the many problems in adults with
      ADHDs, our research focused on the deficits in the processing of nonverbal cues,
      such as gaze direction and the emotional value of others' faces. In Experiment 1,
      a cue display containing a face with emotional value and gaze direction was
      followed by a target display containing two faces located on the left and right
      side of the display. The participant's task was to make an anti-saccade opposite
      to the gaze direction if the cue face was not emotionally neutral. ADHD
      tendencies showed more overall errors than controls in making anti-saccades.
      Based on the hypothesis that the exposure duration of the cue display in
      Experiment 1 may have been too long, we presented the cue and target display
      simultaneously to prevent participants from preparing saccades in advance.
      Participants in Experiment 2 were asked to make either a pro-saccade or an anti
      saccade depending on the emotional value of the central cue face. Interestingly,
      significant group differences were observed for errors of omission and
      commission. In addition, a significant three-way interaction among groups, cue
      emotion, and target gaze direction suggests that the emotional recognition and
      gaze control systems might somehow be interconnected. The result also shows that
      ADHDs are more easily distracted by a task-irrelevant gaze direction. Taken
      together, these results suggest that tasks requiring both response inhibition
      (anti-saccade) and gaze-emotion recognition might be useful in developing a
      diagnostic test for discriminating adults with ADHDs from healthy adults. 

PMID- 25993913
TI  - Directional and color preference in adult zebrafish: Implications in behavioral
      and learning assays in neurotoxicology studies.
AB  - The zebrafish (Danio rerio) is a useful vertebrate model organism for
      neurological studies. While a number of behavior and learning assays are recently
      reported in the literature for zebrafish, many of these assays are still being
      refined. The initial purpose of this study was to apply a published T-maze assay
      for adult zebrafish that measures how quickly an organism can discriminate
      between different color stimuli after receiving reinforcement to measure learning
      in a study investigating the later life impacts of developmental Pb exposure. The
      original results were inconclusive as the control group showed a directional and
      color preference. To assess directional preference further, a three-chambered
      testing apparatus was constructed and rotated in several directions. The
      directional preference observed in males was alleviated by rotating the arms
      pointing west and east. In addition, color preference was investigated using all
      combinations of five different colors (orange, yellow, green, blue and purple).
      With directional preference alleviated results showed that both male and female
      zebrafish preferred colors of shorter wavelengths. An additional experiment
      tested changes in color preference due to developmental exposure to Pb in adult
      male zebrafish. Results revealed that Pb-exposed males gained and lost certain
      color preferences compared to control males and the preference for short
      wavelengths was decreased. Overall, these results show that consideration and
      pretesting should be completed before applying behavioral and learning assays
      involving adult zebrafish to avoid innate preferences and confounding changes in
      neurotoxicology studies and that developmental Pb exposure alters color
      preferences in adult male zebrafish.

PMID- 25993914
TI  - Sterilization of polydimethylsiloxane surface with Chinese herb extract: a new
      antibiotic mechanism of chlorogenic acid.
AB  - Coating of polydimethylsiloxane (PDMS) surface with a traditional Chinese herb
      extract chlorogenic acid (CA) solves the contemporary problem of sterilization of
      PDMS surface. The E. coli grows slower and has a higher death rate on the CA
      coated PDMS surfaces. A smoother morphology of these E. coli cell wall is
      observed by atomic force microscopy (AFM). Unlike the reported mechanism, where
      CA inhibits bacterial growth by damaging the cell membrane in the bulk solution,
      we find the CA-coated PDMS surface also decreases the stiffness of the cell wall.
      A decrease in the Young's modulus of the cell wall from 3 to 0.8 MPa is reported.
      Unexpectedly, the CA effect on the swarming ability and the biofilm stability of
      the bacteria can be still observed, even after they have been removed from the CA
      environment, indicating a decrease in their resistance to antibiotics for a
      prolonged time. The CA-coated PDMS surface shows better antibiotic effect against
      three types of both Gram-positive and Gran-negative bacteria than the gentamicin
      coated PDMS surface. Coating of CA on PDMS surface not only solves the problem of
      sterilization of PDMS surface, but also shines light on the application of
      Chinese traditional herbs in scientific research.

PMID- 25993915
TI  - What are kids getting into these days? A retrospective chart review of substance
      use presentations to a Canadian pediatric emergency department.
AB  - OBJECTIVES: Goals for this study were to characterize the substances being used
      by youth who presented to an emergency department (ED), their demographic
      descriptors, and to describe the associated acute morbidity and mortality.
      METHODS: We conducted a retrospective review of all youth, ages 10-16 years, who
      presented to a pediatric ED with complaints related to recreational drug use
      (n=641) for 2 years ending on December 31, 2009. RESULTS: The median age of
      patients was 15 years; 56% were female. Six percent of patients were homeless,
      and 21% were wards of the state. The most frequent ingestions included ethanol
      (74%), marijuana (20%), ecstasy (19%), and medications (15%). Over one third of
      patients had ingested two or more substances. Ninety percent of patients were
      brought to the ED by the emergency medical services; 63% of these activations
      were by non-acquaintances. Of the 47% of youth who presented with a decreased
      level of consciousness, half had a Glasgow Coma Scale less than 13. The Canadian
      Triage and Acuity Scale score was 1 or 2 for 44% of patients. Sixty-eight percent
      received IV fluids, 42% received medication, and 4% were intubated. The admission
      rate was 9%. CONCLUSIONS: Youth who presented to the ED for substance use
      represented a socially vulnerable population whose use of recreational substances
      resulted in high medical acuity and significant morbidity. Improved clinical
      identification of such high-risk youth and subsequent design of interventions to
      address problematic substance use and social issues are urgently needed to
      complement the acute medical care that youth receive.

PMID- 25993916
TI  - [Determination of hyperregeneratory esophagopathy in dogs with clinical signs
      attributable to esophageal disease].
AB  - OBJECTIVE: It was hypothesized that typical characteristics of hyperregeneratory
      esophagopathy (HRE) in humans such as basal cell hyperplasia and elongation of
      stromal papillae are also histologically detectable in canine esophageal
      epithelium, and that these changes are associated with clinical signs and
      endoscopic findings suggesting gastroesophageal reflux (GER). MATERIAL AND
      METHODS: Sixty-five adult dogs with clinical signs attributable to esophageal
      disease underwent esophagoscopy and biopsy. Clinical signs suggesting GER
      (regurgitation, ptyalism, painful discomfort) were prospectively evaluated
      through a questionnaire. Endoscopic mucosal alterations suggesting GER such as
      minimal endoscopic changes and obvious mucosal defects were assessed via video
      endoscopy. Biopsy specimens obtained from the esophageal squamous epithelium were
      evaluated histologically. The squamous epithelium's substructures of esophageal
      biopsies were quantitatively assessed through microscopic morphometry. RESULTS:
      Esophageal squamous epithelium was considered normal in 48 dogs, and HRE was
      detected histologically in 17 dogs; both pathognomonic changes (basal cell
      hyperplasia, elongation of stromal papillae) were consistently present.
      Morphometrically assessed stromal papillary length and basal cell layer thickness
      was significantly (each, p < 0.0001) higher in the 17 dogs with HRE than in the
      48 dogs without HRE, respectively. Overall, clinical signs suggesting GER were
      significantly (p = 0.02) more frequently encountered and regurgitation was
      significantly (p = 0.009) more common in the 17 dogs with HRE than in the 48 dogs
      without HRE. Similarly, endoscopic changes were significantly (p = 0.002) more
      frequently observed and minimal endoscopic changes suggesting GER were
      significantly (p = 0.004) more common in 17 dogs with HRE than in the 48 dogs
      without HRE. CONCLUSION AND CLINICAL RELEVANCE: Typical characteristics of
      hyperregeneratory esophagopathy in humans are also histologically detectable in
      canine esophageal epithelium. Histological changes are associated with clinical
      signs and endoscopic findings suggesting GER.

PMID- 25993917
TI  - Sexual recombination as a tool for engineering industrial Penicillium chrysogenum
      strains.
AB  - The recent discovery and functional characterization of opposite mating-type loci
      in the industrial penicillin producer Penicillium chrysogenum demonstrated their
      regulatory role in sexual as well as asexual development. Subsequent experiments
      further showed that a sexual life cycle can be induced in P. chrysogenum that was
      for long believed to reproduce exclusively by asexual propagation. Finally,
      crossing of wild type and production strains resulted in the generation of
      recombinant ascospore isolates. We predict from these recent findings that
      recombinant progeny for industrial applications can be obtained by sexual
      crossings and discuss experimental difficulties that occur when parental strains
      with karyotype heterogeneity are used for mating. 

PMID- 25993918
TI  - Reproductive behavior of the great hornbill (Buceros bicornis).
AB  - Great hornbills (Buceros bicornis) are a long-lived, monogamous species that
      forms strong pair-bonds, and mate compatibility is thought to be important for
      successful reproduction. Within AZA, great hornbills are listed as a red SSP. The
      population consists of a limited number of individuals that do not breed
      reliably, and improving reproduction is a top priority for the Coraciiformes TAG.
      To better understand mating behavior and evaluate mate compatibility, this study
      documented the behavior of pairs of great hornbills during and immediately after
      courtship. Using live observations, the study followed one female, an experienced
      and successful breeder, as she was paired with four successive males over 11
      breeding seasons. Initially, males frequently vocalized, investigated the nest,
      and approached the female. As the female spent more time in the nest, these
      behaviors were replaced by regurgitation and food offering. The female was most
      often observed plastering and vocalizing. Behavioral differences between
      successful and unsuccessful pairs, possibly indicative of pair compatibility,
      included rates of approaching, billing, and biting. Numerous behaviors occurred
      more frequently during years that a chick hatched, including pseudoregurgitation,
      regurgitation, offering food items, and nest investigation. Males also spent more
      time in proximity to both the female and the nest during years that a chick
      hatched. Together, these results suggest that the amount of time pairs spend in
      proximity, the amount of time a male spends near the nest, and the frequency of
      certain behaviors may help evaluate compatibility and the likelihood of
      successful reproduction for pairs of great hornbills.

PMID- 25993919
TI  - A patent problem.

PMID- 25993920
TI  - Publish or perish.

PMID- 25993921
TI  - The kill switch.

PMID- 25993922
TI  - No more hidden solutions in bioinformatics.

PMID- 25993934
TI  - Engineered yeast paves way for home-brew heroin.

PMID- 25993935
TI  - Short-term aid has long-term impact.

PMID- 25993936
TI  - Congress seeks to quash patent trolls.

PMID- 25993938
TI  - Billion-dollar collider gets thumbs up.

PMID- 25993937
TI  - UK slack on misconduct reports.

PMID- 25993939
TI  - Russia turns screw on science foundation.

PMID- 25993941
TI  - Quantum physics: What is really real?

PMID- 25993940
TI  - Reproducibility crisis: Blame it on the antibodies.

PMID- 25993942
TI  - Drugs: Regulate 'home-brew' opiates.

PMID- 25993943
TI  - Sustainability: Clean cooking empowers women.

PMID- 25993946
TI  - Correction.

PMID- 25993948
TI  - Mutational technologies: Engage public in gene-editing policy.

PMID- 25993949
TI  - Water: Halt India's groundwater loss.

PMID- 25993950
TI  - Clinical practice: Blood-transfusion decisions not simple.

PMID- 25993951
TI  - Water: A drought plan for biodiversity.

PMID- 25993952
TI  - Water: Megacities running dry in Brazil.

PMID- 25993953
TI  - Alexander Rich (1924-2015).

PMID- 25993954
TI  - Archaeology: Tools go back in time.

PMID- 25993955
TI  - Quantum physics: Squeezed ions in two places at once.

PMID- 25993956
TI  - Stem cells: Asymmetric rejuvenation.

PMID- 25993957
TI  - Materials science: Magnetic alloys break the rules.

PMID- 25993958
TI  - Stem cells: Equilibrium established.

PMID- 25993959
TI  - Clarification.

PMID- 25993960
TI  - The crystallography of correlated disorder.
AB  - Classical crystallography can determine structures as complicated as multi
      component ribosomal assemblies with atomic resolution, but is inadequate for
      disordered systems--even those as simple as water ice--that occupy the complex
      middle ground between liquid-like randomness and crystalline periodic order.
      Correlated disorder nevertheless has clear crystallographic signatures that map
      to the type of disorder, irrespective of the underlying physical or chemical
      interactions and material involved. This mapping hints at a common language for
      disordered states that will help us to understand, control and exploit the
      disorder responsible for many interesting physical properties.

PMID- 25993962
TI  - A strong ultraviolet pulse from a newborn type Ia supernova.
AB  - Type Ia supernovae are destructive explosions of carbon-oxygen white dwarfs.
      Although they are used empirically to measure cosmological distances, the nature
      of their progenitors remains mysterious. One of the leading progenitor models,
      called the single degenerate channel, hypothesizes that a white dwarf accretes
      matter from a companion star and the resulting increase in its central pressure
      and temperature ignites thermonuclear explosion. Here we report observations with
      the Swift Space Telescope of strong but declining ultraviolet emission from a
      type Ia supernova within four days of its explosion. This emission is consistent
      with theoretical expectations of collision between material ejected by the
      supernova and a companion star, and therefore provides evidence that some type Ia
      supernovae arise from the single degenerate channel. 

PMID- 25993961
TI  - 3.3-million-year-old stone tools from Lomekwi 3, West Turkana, Kenya.
AB  - Human evolutionary scholars have long supposed that the earliest stone tools were
      made by the genus Homo and that this technological development was directly
      linked to climate change and the spread of savannah grasslands. New fieldwork in
      West Turkana, Kenya, has identified evidence of much earlier hominin
      technological behaviour. We report the discovery of Lomekwi 3, a 3.3-million-year
      old archaeological site where in situ stone artefacts occur in spatiotemporal
      association with Pliocene hominin fossils in a wooded palaeoenvironment. The
      Lomekwi 3 knappers, with a developing understanding of stone's fracture
      properties, combined core reduction with battering activities. Given the
      implications of the Lomekwi 3 assemblage for models aiming to converge
      environmental change, hominin evolution and technological origins, we propose for
      it the name 'Lomekwian', which predates the Oldowan by 700,000 years and marks a
      new beginning to the known archaeological record. 

PMID- 25993963
TI  - No signature of ejecta interaction with a stellar companion in three type Ia
      supernovae.
AB  - Type Ia supernovae are thought to be the result of a thermonuclear runaway in
      carbon/oxygen white dwarfs, but it is uncertain whether the explosion is
      triggered by accretion from a non-degenerate companion star or by a merger with
      another white dwarf. Observations of a supernova immediately following the
      explosion provide unique information on the distribution of ejected material and
      the progenitor system. Models predict that the interaction of supernova ejecta
      with a companion star or circumstellar debris lead to a sudden brightening
      lasting from hours to days. Here we present data for three supernovae that are
      likely to be type Ia observed during the Kepler mission with a time resolution of
      30 minutes. We find no signatures of the supernova ejecta interacting with nearby
      companions. The lack of observable interaction signatures is consistent with the
      idea that these three supernovae resulted from the merger of binary white dwarfs
      or other compact stars such as helium stars. 

PMID- 25993964
TI  - Spin-motion entanglement and state diagnosis with squeezed oscillator
      wavepackets.
AB  - Mesoscopic superpositions of distinguishable coherent states provide an analogue
      of the 'Schrodinger's cat' thought experiment. For mechanical oscillators these
      have primarily been realized using coherent wavepackets, for which the
      distinguishability arises as a result of the spatial separation of the superposed
      states. Here we demonstrate superpositions composed of squeezed wavepackets,
      which we generate by applying an internal-state-dependent force to a single
      trapped ion initialized in a squeezed vacuum state with nine decibel reduction in
      the quadrature variance. This allows us to characterize the initial squeezed
      wavepacket by monitoring the onset of spin-motion entanglement, and to verify the
      evolution of the number states of the oscillator as a function of the duration of
      the force. In both cases we observe clear differences between displacements
      aligned with the squeezed and anti-squeezed axes. We observe coherent revivals
      when inverting the state-dependent force after separating the wavepackets by more
      than 19 times the ground-state root mean squared extent, which corresponds to 56
      times the root mean squared extent of the squeezed wavepacket along the
      displacement direction. Aside from their fundamental nature, these states may be
      useful for quantum metrology or quantum information processing with continuous
      variables. 

PMID- 25993965
TI  - Non-Joulian magnetostriction.
AB  - All magnets elongate and contract anisotropically when placed in a magnetic
      field, an effect referred to as Joule magnetostriction. The hallmark of Joulian
      magnetostriction is volume conservation, which is a broader definition applicable
      to self-accommodation of ferromagnetic, ferroelectric or ferroelastic domains in
      all functional materials. Here we report the discovery of 'giant' non-volume
      conserving or non-Joulian magnetostriction (NJM). Whereas Joulian strain is
      caused by magnetization rotation, NJM is caused by facile (low-field)
      reorientation of magnetoelastically and magnetostatically autarkic (self
      sufficient) rigid micro-'cells', which define the adaptive structure, the origin
      of which is proposed to be elastic gradients ultimately caused by charge/spin
      density waves. The equilibrium adaptive cellular structure is responsible for
      long-sought non-dissipative (hysteresis-free), linearly reversible and isotropic
      magnetization curves along all directions within a single crystal. Recently
      discovered Fe-based high magnetostriction alloys with special thermal history are
      identified as the first members of this newly discovered magnetic class. The NJM
      paradigm provides consistent interpretations of seemingly confounding properties
      of Fe-based alloys, offers recipes to develop new highly magnetostrictive
      materials, and permits simultaneously large actuation in longitudinal and
      transverse directions without the need for stacked composites. 

PMID- 25993966
TI  - Corrigendum: Three keys to the radiation of angiosperms into freezing
      environments.

PMID- 25993967
TI  - Corrigendum: Oxidant stress evoked by pacemaking in dopaminergic neurons is
      attenuated by DJ-1.

PMID- 25993970
TI  - Doubtful pathways to cold tolerance in plants.

PMID- 25993969
TI  - Wild-type microglia do not reverse pathology in mouse models of Rett syndrome.

PMID- 25993971
TI  - Zanne et al. reply.

PMID- 25993972
TI  - The Epidemiology, Clinical Manifestations, and Management of Chagas Heart
      Disease.
AB  - Chagas disease results from infection by the protozoan parasite Trypanosoma cruzi
      and is endemic in Latin America. T cruzi is most commonly transmitted through the
      feces of an infected triatomine, but can also be congenital, via contaminated
      blood transfusion or through direct oral contact. In the acute phase, the disease
      can cause cardiac derangements such as myocarditis, conduction system
      abnormalities, and/or pericarditis. If left untreated, the disease advances to
      the chronic phase. Up to one-half of these patients will develop a
      cardiomyopathy, which can lead to cardiac failure and/or ventricular arrhythmias,
      both of which are major causes of mortality. Diagnosis is confirmed by serologic
      testing for specific immunoglobulin G antibodies. Initial treatment consists of
      the antiparasitic agents benznidazole and nifurtimox. The treatment of Chagas
      cardiac disease comprises standard medical therapy for heart failure and
      amiodarone for ventricular arrhythmias, with consideration for implantable
      cardioverter-defibrillator. Chagas disease causes the highest infectious burden
      of any parasitic disease in the Western Hemisphere, and increased awareness of
      this disease is essential to improve diagnosis, enhance management, and reduce
      spread. 

PMID- 25993973
TI  - Fine needle aspiration cytology of histiocytic sarcoma with dendritic cell
      differentiation: a case of transdifferentiation from low-grade follicular
      lymphoma.
AB  - Histiocytic sarcoma (HS) is a rare malignant tumor, and in extraordinary
      circumstances it can be transdifferentiated from a low-grade B-cell lymphoma. In
      our report, a 62-year-old female was initially diagnosed with a low-grade
      follicular lymphoma, and 2 years later she presented with bilateral lung masses
      and lymphadenopathy. Fine needle aspiration (FNA) of the lung masses revealed
      solid nests of large pleomorphic epithelioid cells. By immunohistochemical
      studies, the tumor cells were positive for histiocytic markers (CD68 and CD163)
      and S100, supporting a diagnosis of HS with dendritic cell differentiation.
      Further fluorescence in situ hybridization (FISH) analyses detected IGH@/BCL2
      rearrangement in both the previous follicular lymphoma and the current HS, which
      was highly suggestive of the clonal relationship between these two tumors. To the
      best of our knowledge, this is the first case of transformation of follicular
      lymphoma into HS diagnosed by FNA of lung masses.

PMID- 25993974
TI  - Isolation of Escherichia albertii from Raw Chicken Liver in Fukuoka City, Japan.

PMID- 25993975
TI  - Middle East respiratory syndrome coronavirus infection not found in camels in
      Japan.

PMID- 25993976
TI  - Outbreak of human bocavirus 1 infection in young children in Toyama, Japan.

PMID- 25993977
TI  - Synthesis of the 19th ArgoSpine Symposium.
AB  - After a short introduction of the meeting by the President 2015, Wilco Peul, the
      opening lecture was delivered by Bart Koes, who dealt with Health Technology
      Assessment and Guidelines. Then, it was the turn of Carmen Vleggert to show
      whether there was any Evidence for the Use of Implants in Spinal Stenosis. The
      final presentation of this session was delivered by Bjorn Stromqvist who dealt
      with Surgery for Lumbar Disc Herniation, patients' selection and outcomes.
      Developing the subject of "Do Not's", Jeremy Fairbank described the UK experience
      for Low Back Pain. Yves Coppens then took over and further elaborated on "Lucy's
      legacy". Prof. Coppens recalled that Lucy is a partial skeleton of a pre-human
      found in Ethiopia among other remains. Prof. Alan Crockard offered what he called
      "a whimsical view" of his practice of Craniocervical Surgery. Wafa Skalli was
      asked to speak about Finite Element Analysis of the Spine and Arts et Metiers
      Paris Tech where there is a long tradition of close collaboration between
      engineers and clinicians. Rune Hedlund, who will serve as 2016 Symposium
      President, further elaborated on Scoliosis with a focus on Unsolved Issues in
      Adolescent Idiopathic Scoliosis Treatment. 

PMID- 25993978
TI  - C-O cleavage of aromatic oxygenates over ruthenium catalysts. A computational
      study of reactions at step sites.
AB  - We studied the C-O cleavage of phenolate and catecholate at step sites of a Ru
      catalyst using periodic DFT methods at the GGA level. Both C-O scission steps are
      associated with activation barriers of about 75 kJ mol(-1), hence are
      significantly more facile than the analogous reactions on Ru terraces. With these
      computational results, we offer an interpretation of recent experiments on the
      hydrodeoxygenation of guaiacol (2-methoxyphenol) over Ru/C. We hypothesize that
      the experimentally observed dependency of the product selectivity on the H2
      pressure is related to the availability of step sites on a Ru catalyst. 

PMID- 25993980
TI  - A Brief Examination of Integrated Care in Undergraduate Medical Education.
AB  - OBJECTIVE: This study examines how behavioral and physical health are currently
      integrated in undergraduate medical education, both in the classroom and during
      clinical rotations. METHODS: Members of the Association of Directors of Medical
      Student Education in Psychiatry (n = 215) were invited to complete a short survey
      on the integration of physical and behavioral health at their institution.
      RESULTS: In addition to undergraduate medical courses traditionally taught by
      psychiatrists, behavioral science topics are often addressed in neurology,
      reproduction, and doctoring courses. During clinical rotations, behavioral health
      topics are most likely taught during the family medicine clerkship and,
      conversely, least likely during the surgery clerkship; furthermore, behavioral
      health topics are much less likely to be taught by psychiatrists during clinical
      rotations. CONCLUSIONS: Integration of behavioral and physical health in medical
      education is beginning to occur in a meaningful context.

PMID- 25993979
TI  - Converging nuclear magnetic shielding calculations with respect to basis and
      system size in protein systems.
AB  - Ab initio chemical shielding calculations greatly facilitate the interpretation
      of nuclear magnetic resonance (NMR) chemical shifts in biological systems, but
      the large sizes of these systems requires approximations in the chemical models
      used to represent them. Achieving good convergence in the predicted chemical
      shieldings is necessary before one can unravel how other complex structural and
      dynamical factors affect the NMR measurements. Here, we investigate how to
      balance trade-offs between using a better basis set or a larger cluster model for
      predicting the chemical shieldings of the substrates in two representative
      examples of protein-substrate systems involving different domains in tryptophan
      synthase: the N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F9) ligand
      which binds in the alpha active site, and the 2-aminophenol quinonoid
      intermediate formed in the beta active site. We first demonstrate that a
      chemically intuitive three-layer, locally dense basis model that uses a large
      basis on the substrate, a medium triple-zeta basis to describe its hydrogen
      bonding partners and/or surrounding van der Waals cavity, and a crude basis set
      for more distant atoms provides chemical shieldings in good agreement with much
      more expensive large basis calculations. Second, long-range quantum mechanical
      interactions are important, and one can accurately estimate them as a small-basis
      correction to larger-basis calculations on a smaller cluster. The combination of
      these approaches enables one to perform density functional theory NMR chemical
      shift calculations in protein systems that are well-converged with respect to
      both basis set and cluster size.

PMID- 25993982
TI  - Type III secretion as a generalizable strategy for the production of full-length
      biopolymer-forming proteins.
AB  - Biopolymer-forming proteins are integral in the development of customizable
      biomaterials, but recombinant expression of these proteins is challenging. In
      particular, biopolymer-forming proteins have repetitive, glycine-rich domains
      and, like many heterologously expressed proteins, are prone to incomplete
      translation, aggregation, and proteolytic degradation in the production host.
      This necessitates tailored purification processes to isolate each full-length
      protein of interest from the truncated forms as well as other contaminating
      proteins; owing to the repetitive nature of these proteins, the truncated
      polypeptides can have very similar chemistry to the full-length form and are
      difficult to separate from the full-length protein. We hypothesized that
      bacterial expression and secretion would be a promising alternative option for
      biomaterials-forming proteins, simplifying isolation of the full-length target
      protein. By using a selective secretion system, truncated forms of the protein
      are not secreted and thus are not found in the culture harvest. We show that a
      synthetically upregulated type III secretion system leads to a general increase
      in secretion titer for each protein that we tested. Moreover, we observe a
      substantial enhancement in the homogeneity of full-length forms of pro-resilin,
      tropo-elastin crosslinking domains, and silk proteins produced in this manner, as
      compared with proteins purified from the cytosol. Secretion via the type III
      apparatus limits co-purification of truncated forms of the target protein and
      increases protein purity without extensive purification steps. Demonstrating the
      utility of such a system, we introduce several modifications to resilin-based
      peptides and use an un-optimized, single-column process to purify these proteins.
      The resulting materials are of sufficiently high quantity and yield for the
      production of antimicrobial hydrogels with highly reproducible rheological
      properties. The ease of this process and its applicability to an array of
      engineered biomaterial-forming peptides lend support for the application of
      bacterial expression and secretion for other proteins that are traditionally
      difficult to express and isolate from the bacterial cytoplasm. Biotechnol.
      Bioeng. 2016;113: 2313-2320. (c) 2015 Wiley Periodicals, Inc.

PMID- 25993983
TI  - Ranging, activity budget, and diet composition of red titi monkeys (Callicebus
      cupreus) in primary forest and forest edge.
AB  - Deforestation and fragmentation of tropical rainforests are increasingly creating
      forest edges and corresponding edge effects. Furthermore, primary forest is
      increasingly being replaced by secondary forest. The presence of high population
      densities of titi monkeys in fragmented and secondary forests suggests that they
      are capable of adapting to such habitat alterations. The aim of our study was to
      examine the ability of the red titi monkey (Callicebus cupreus) to adapt to
      forest edges and secondary forest. We compared home-range use, activity budgets,
      and diet composition in two groups of monkeys: one in primary forest and the
      other in primary forest with a long edge bordering secondary forest. The latter
      group avoided the secondary forest and used the edge in proportion to its
      availability. Groups did not differ in activity budgets but did show slight
      differences in diet composition. Taken together, our results suggest that there
      are no major effects of forest edges and secondary forest on red titi monkeys;
      however, given the relatively short study period, generalizations should be
      avoided until more comparative data become available. Furthermore, the age or
      successional stage of the secondary forest must be taken into consideration when
      drawing conclusions about its suitability as a primate habitat. 

PMID- 25993981
TI  - Synovial mesenchymal stem cells promote meniscus regeneration augmented by an
      autologous Achilles tendon graft in a rat partial meniscus defect model.
AB  - Although meniscus defects and degeneration are strongly correlated with the later
      development of osteoarthritis, the promise of regenerative medicine strategies is
      to prevent and/or delay the disease's progression. Meniscal reconstruction has
      been shown in animal models with tendon grafting and transplantation of
      mesenchymal stem cells (MSCs); however, these procedures have not shown the same
      efficacy in clinical studies. Here, our aim was to investigate the ability of
      tendon grafts pretreated with exogenous synovial-derived MSCs to prevent
      cartilage degeneration in a rat partial meniscus defect model. We removed the
      anterior half of the medial meniscus and grafted autologous Achilles tendons with
      or without a 10-minute pretreatment of the tendon with synovial MSCs. The
      meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5).
      Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological
      scores for regenerated menisci were better in the tendon + MSC group than in the
      other two groups at 4 and 8 weeks. Both macroscopic and histological scores for
      articular cartilage were significantly better in the tendon + MSC group at 8
      weeks. Implanted synovial MSCs survived around the grafted tendon and native
      meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+,
      and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed
      that transplanted synovial MSCs retained their MSC properties at 7 days and host
      synovial tissue also contained cells with MSC characteristics. Synovial MSCs
      promoted meniscus regeneration augmented by autologous Achilles tendon grafts and
      prevented cartilage degeneration in rats.

PMID- 25993984
TI  - Lung ultrasound: a useful tool in diagnosis and management of bronchiolitis.
AB  - BACKGROUND: Clinical assessment is the gold standard for diagnosis of
      bronchiolitis. To date, only one study found LUS (Lung Ultrasound) to be a
      valuable tool in the diagnosis of bronchiolitis. Aim of this study is to evaluate
      the accuracy of lung ultrasonography in the diagnosis and management of
      bronchiolitis in infants. METHODS: This was an observational cohort study of
      infants admitted to our Pediatric Unit with suspected bronchiolitis. A physical
      examination and lung ultrasound scans were performed on each patient. Diagnosis
      and grading of bronchiolitis was assessed according to a clinical and a
      ultrasound score. An exploratory analysis was used to assess correspondence
      between the lung ultrasound findings and the clinical evaluation and to evaluate
      the inter-observer concordance between the two different sonographs. RESULTS: One
      hundred six infants were studied (average age 71 days). According to our clinical
      score, 74 infants had mild bronchiolitis, 30 had moderate bronchiolitis and two
      had severe bronchiolitis. 25 infants composed the control group. Agreement
      between the clinical and sonographic diagnosis was good (90.6%) with a
      statistically significant inter-observer ultrasound diagnosis concordance
      (89.6%). Lung ultrasound permits the identification of infants who are in need of
      supplementary oxygen with a specificity of 98.7%, a sensitivity of 96.6%, a
      positive predictive value of 96.6% and a negative predictive value of 98.7%. An
      aberrant ultrasound lung pattern in posterior chest area was collected in 86% of
      infants with bronchiolitis. In all patients clinical improvement at discharge was
      associated with disappearance of the previous LUS findings. Subpleural lung
      consolidation of 1 cm or more in the posterior area scan and a quantitative
      classification of interstitial syndrome based on intercostal spaces involved
      bilaterally, good correlate with bronchiolitis severity and oxygen use.
      CONCLUSIONS: The lung ultrasound findings strictly correlate with the clinical
      evaluations in infants with bronchiolitis and permit the identification of
      infants who are in need of supplementary oxygen with high specificity. Scans of
      the posterior area are more indicative in ascertaining the severity of
      bronchiolitis. TRIAL REGISTRATION: Clinical Trial Registration NCT01993797.

PMID- 25993985
TI  - TGF-beta1 expression is associated with invasion and metastasis of intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta is involved in many physiologic
      processes, it often promotes metastasis, and its high expression is correlated
      with poor prognosis. In the present study, we analyzed the correlation between
      transforming growth factor beta 1 (TGF-beta1) expression and prognosis in
      intrahepatic cholangiocarcinoma. RESULTS: We examined the expression of TGF-beta1
      in 78 intrahepatic cholangiocarcinomas by immunohistochemistry and correlated the
      expression with clinicopathological parameters. TGF-beta1 was expressed in 37 of
      78 (47.4%) intrahepatic cholangiocarcinomas. The expression of TGF-beta1 was
      significantly correlated with lymph node metastasis, distant metastasis, and
      tumour recurrence. Patients with TGF-beta1-positive tumours had significantly
      shorter survival time. In a multivariant analysis, the expression of TGF-beta1
      and the tumour stage were independent prognostic factors. CONCLUSIONS: Our data
      suggest that expression of TGF-beta1 is a novel prognostic marker for
      intrahepatic cholangiocarcinoma.

PMID- 25993986
TI  - Development of an improved competitive ELISA based on a monoclonal antibody
      against lipopolysaccharide for the detection of bovine brucellosis.
AB  - BACKGROUND: Brucellosis is the most common bacterial zoonosis, and serological
      tests are routinely used in brucellosis control and eradication programs. In
      order to improve the accuracy of serological diagnostic method used in bovine
      brucellosis detection, this study developed an improved competitive ELISA with
      higher specificity and good sensitivity. RESULTS: This study prepared 12
      monoclonal antibodies against smooth Brucella lipopolysaccharide. One monoclonal
      antibody 3 F9, presented C epitope specificity, was used to develop a competitive
      ELISA for the serological detection of bovine brucellosis. The competitive ELISA,
      a commercial competitive ELISA kit, the rose-bengal plate agglutination test, and
      a microplate agglutination test were all used in the detection of 6 hyperimmune
      antisera against other commonly cross-reacted bacterial pathogens and 110
      clinical bovine serum samples. The results of the test comparisons indicated that
      the competitive ELISA had higher specificity than the commercial competitive
      ELISA kit and RBT, and comparable sensitivity with the commercial ELISA kit.
      CONCLUSIONS: This study provided a valuable detection tool with high specificity
      and good sensitivity, which prevent the wrong-culling of bovines in the
      eradication campaigns of bovine brucellosis.

PMID- 25993988
TI  - Worsening disability in older people: a trigger for palliative care.

PMID- 25993987
TI  - Neuroprotective properties of dehydroepiandrosterone-sulfate and its relationship
      to interleukin 6 after aneurysmal subarachnoid hemorrhage: a prospective cohort
      study.
AB  - INTRODUCTION: The established neuroprotective property of the sex steroid
      precursor dehydroepiandrosterone-sulfate (DHEAS) has not yet been investigated in
      the context of aneurysmal subarachnoid hemorrhage (aSAH). The influence of DHEAS
      on inflammatory response resulting in modulation of interleukin 6 (IL-6)
      synthesis has been shown. Here, we evaluate DHEAS serum levels after aSAH (day 0
      14) and levels of IL-6 related to functional outcome at discharge and at six
      months. METHODS: A complete data set (DHEAS and IL-6 serum levels for days 0, 1,
      4, 7, 10 and 14 after aSAH) and outcome assessment at discharge according to
      modified Rankin Scale score (mRS) was available for 53 patients of the initially
      screened cohort (n = 109). Outcome assessment six months after aSAH was obtained
      from 41 patients. Logarithmized levels of DHEAS and IL-6 were related to
      dichotomized functional outcome either assessed at discharge or at six months. A
      mixed between-within subjects ANOVA was applied for statistical analysis (SPSS
      21.0). RESULTS: DHEAS and IL-6 levels across time were related to functional
      outcome. Regarding outcome assessment at discharge and at six months after aSAH,
      DHEAS levels (transformed to square root for statistical purposes) were
      considerably higher in patients with favorable outcome (mRS 0-2) (p = .001; p =
      .020). Inversely, in patients with favorable outcome either at discharge or six
      months after aSAH, lower IL-6 levels (logarithmized for statistical purposes)
      were observed across time (both p < .001). CONCLUSION: We provide new evidence
      that DHEAS is associated with protective properties resulting in improvement of
      functional outcome after aSAH, possibly by influencing the inflammatory response
      after aSAH shown in the decreasing IL-6 serum levels. But the results for outcome
      six months after SAH are limited due to a high drop-out rate.

PMID- 25993989
TI  - Cyclin A2 modulates EMT via beta-catenin and phospholipase C pathways.
AB  - We have previously demonstrated that Cyclin A2 is involved in cytoskeletal
      dynamics, epithelial-mesenchymal transition (EMT) and metastasis. This phenotype
      was potentiated by activated oncogenic H-Ras. However, the mechanisms governing
      EMT in these cells have not yet been elucidated. Here, we dissected the pathways
      that are responsible for EMT in cells deficient for Cyclin A2. In Cyclin A2
      depleted normal murine mammary gland (NMuMG) cells expressing RasV12, we found
      that beta-catenin was liberated from the cell membrane and cell-cell junctions
      and underwent nuclear translocation and activation. Components of the canonical
      wingless (WNT) pathway, including WNT8b, WNT10a, WNT10b, frizzled 1 and 2 and
      TCF4 were upregulated at the messenger RNA and protein levels following Cyclin A2
      depletion. However, suppression of the WNT pathway using the acetyltransferase
      porcupine inhibitor C59 did not reverse EMT whereas a dominant negative form of
      TCF4 as well as inhibition of phospholipase C using U73122 were able to do so.
      This suggests that a WNT-independent mechanism of beta-catenin activation via
      phospholipase C is involved in the EMT induced by Cyclin A2 depletion. Our
      findings will broaden our knowledge on how Cyclin A2 contributes to EMT and
      metastasis. 

PMID- 25993990
TI  - Trolox enhances follicular survival after ovarian tissue autograft in squirrel
      monkey (Saimiri collinsi).
AB  - The aim of this study was to evaluate ovarian tissue pre-treatment with 50 uM
      Trolox followed by heterotopic transplantation in squirrel monkeys (Saimiri
      collinsi) and to assess tissue functionality via immunohistochemical analysis of
      the stroma and ovarian follicles. Five healthy and sexually mature squirrel
      monkey (Saimiri collinsi) females were used. Heterotopic autografting of fresh
      ovarian tissue with or without previous exposure to the antioxidant Trolox was
      performed and grafts were recovered for analysis 7 days later. Tissue
      vascularisation was confirmed by both macroscopic inspection and cluster of
      differentiation 31 (CD31) staining. Trolox prevented massive follicular
      activation and kept the percentages of morphologically normal follicles higher
      than in untreated grafts. Expression of anti-Mullerian hormone in developing
      follicles was observed only in controls and Trolox-treated grafts. Also,
      immunostaining for growth differentiation factor-9 was positive only in
      primordial follicles from controls and from Trolox-treated grafts. Although
      Trolox improved follicular quality and avoided apoptosis in stromal cells,
      ovarian tissue fibrosis was increased in Trolox-treated grafts, mainly due to an
      increase in collagen Type I synthesis.

PMID- 25993991
TI  - The Association between Metabolic Syndrome and Serum Levels of Adiponectin and
      High Sensitive C Reactive Protein in Gorgan.
AB  - BACKGROUND: The aim of this study was to assess serum levels of highly sensitive
      C-reactive protein (hs-CRP) and adiponectin in subjects with metabolic syndrome
      and control groups. METHODS: There were 40 subjects with metabolic syndrome and
      40 control groups. Mean serum level of adiponectin and high sensitive C reactive
      protein were lower and higher in subjects with metabolic syndrome than control
      groups, respectively. There were significant positive correlation between high
      sensitive C reactive protein and waist circumference, systolic and diastolic
      blood pressure, triglyceride and fasting blood glucose. There were significant
      negative correlation between adiponectin and waist circumference and
      triglyceride. Hs-CRP showed a stronger association with metabolic syndrome than
      adiponectin. RESULTS: Our findings suggest that elevated hs-CRP and reduced
      adiponectin showed positive and negative association with some metabolic syndrome
      components. Hs-CRP showed a stronger association with the metabolic syndrome than
      adiponectin. CONCLUSION: It seems that hs-CRP may play a significant role as a
      risk factor for metabolic syndrome. In this study, in contrast with other
      findings it may suggest that hs-CRP is more important as a diagnostic biomarker
      for metabolic syndrome than adiponectin. These differences may be due to the
      changes in the lifestyle and dietary habits in subjects with metabolic syndrome
      in Gorgan inhabitants. It likes that these subjects do less physical activity and
      use more fatty nutrients. It seems that subjects with metabolic syndrome need to
      change their life style and dietary habits in this area to halt the burden of
      cardiovascular complications.

PMID- 25993993
TI  - A Place at the Table: LTD as a Mediator of Memory Genesis.
AB  - Resolving how our brains encode information requires an understanding of the
      cellular processes taking place during memory formation. Since the 1970s,
      considerable effort has focused on determining the properties and mechanisms
      underlying long-term potentiation (LTP) at glutamatergic synapses and how these
      processes influence initiation of new memories. However, accumulating evidence
      suggests that long-term depression (LTD) of synaptic strength, particularly at
      glutamatergic synapses, is a bona fide learning and memory mechanism in the
      mammalian brain. The known range of mechanisms capable of inducing LTD has been
      extended to those including NMDAR-independent forms, neuromodulator-dependent
      LTD, synaptic depression following stress, and non-synaptically induced forms.
      The examples of LTD observed at the hippocampal CA1 synapse to date demonstrate
      features consistent with LTP, including homo- and heterosynaptic expression,
      extended duration beyond induction (several hours to weeks), and association with
      encoding of distinct types of memories. Canonical mechanisms through which
      synapses undergo LTD include activation of phosphatases, initiation of protein
      synthesis, and dynamic regulation of presynaptic glutamate release and/or
      postsynaptic glutamate receptor endocytosis. Here, we will discuss the pre- and
      postsynaptic changes underlying LTD, recent advances in the identification and
      characterization of novel mechanisms underlying LTD, and how engagement of these
      processes constitutes a cellular analog for the genesis of specific types of
      memories.

PMID- 25993994
TI  - Real-World Medical Cost Avoidance When New Oral Anticoagulants are Used Versus
      Warfarin for Venous Thromboembolism in the United States.
AB  - OBJECTIVE: Real-world medical cost avoidances from a US payer perspective were
      estimated when new oral anticoagulants (NOACs) are used instead of warfarin for
      the treatment of patients with venous thromboembolism (VTE). METHODS: Reductions
      in real-world event rates of recurrent VTE and MB were obtained by applying rate
      reductions from the NOACs versus warfarin trials to the Worcester population.
      Incremental annual medical costs among patients with VTE and MB from a US payer
      perspective were obtained from the literature or claims databases. Differences in
      total medical costs for patients treated with NOACs versus warfarin were then
      estimated. Univariate and Monte Carlo sensitivity analyses were additionally
      carried out. RESULTS: The annual total medical cost avoidances versus warfarin
      were greatest for VTE patients treated with apixaban (-US$4440 per patient-year
      [ppy]), followed by those treated with rivaroxaban (-US$2971 ppy), edoxaban (
      US$1957 ppy), and dabigatran (-US$572 ppy). The medical cost avoidances remained
      consistent under sensitivity analyses. CONCLUSION: Based on real-world data, when
      any of the evaluated NOACs are used instead of warfarin for treatment of patients
      with acute VTE, annual medical costs are reduced. Of the NOACs, apixaban has the
      greatest real-world medical cost avoidance, as its use is associated with
      substantial reductions in both VTE and MB event rates.

PMID- 25993992
TI  - Inhibition of serum- and glucocorticoid-inducible kinase 1 enhances TLR-mediated
      inflammation and promotes endotoxin-driven organ failure.
AB  - Serum- and glucocorticoid-regulated kinase (SGK)1 is associated with several
      important pathologic conditions and plays a modulatory role in adaptive immune
      responses. However, the involvement and functional role of SGK1 in innate immune
      responses remain entirely unknown. In this study, we establish that SGK1 is a
      novel and potent negative regulator of TLR-induced inflammation. Pharmacologic
      inhibition of SGK1 or suppression by small interfering RNA enhances
      proinflammatory cytokine (TNF, IL-12, and IL-6) production in TLR-engaged
      monocytes, a result confirmed in Cre-loxP-mediated SGK1-deficient cells. SGK1
      inhibition or gene deficiency results in increased phosphorylation of IKK,
      IkappaBalpha, and NF-kappaB p65 in LPS-stimulated cells. Enhanced NF-kappaB p65
      DNA binding also occurs upon SGK1 inhibition. The subsequent enhancement of
      proinflammatory cytokines is dependent on the phosphorylation of TGF-beta
      activated kinase 1 (TAK1), as confirmed by TAK1 gene silencing. In vivo relevance
      was established in a murine endotoxin model, in which we found that SGK1
      inhibition aggravates the severity of multiple organ damage and enhances the
      inflammatory response by heightening both proinflammatory cytokine levels and
      neutrophil infiltration. These findings have identified an anti-inflammatory
      function of SGK1, elucidated the underlying intracellular mechanisms, and
      establish, for the first time, that SGK1 holds potential as a novel target for
      intervention in the control of inflammatory diseases.

PMID- 25993996
TI  - Identification of Suspected Ruptured Atherosclerotic Plaque in Acute Ischemic
      Stroke on (18)F-Sodium Fluoride Positron Emission Tomography-Computed Tomography.

PMID- 25993995
TI  - Alternation of histone and DNA methylation in human atherosclerotic carotid
      plaques.
AB  - Little is known about epigenetics and its possible role in atherosclerosis. We
      here analysed histone and DNA methylation and the expression of corresponding
      methyltransferases in early and advanced human atherosclerotic carotid lesions in
      comparison to healthy carotid arteries. Western Blotting was performed on carotid
      plaques from our biobank with early (n=60) or advanced (n=60) stages of
      atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation
      patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions,
      di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly
      decreased compared to control arteries. Immunohistochemistry revealed an
      increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a
      decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and
      reduced di-methylated H3K27 in inflammatory cells in advanced versus early
      atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and
      G9a was increased in advanced versus early atherosclerosis. Genomic DNA
      hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was
      observed in early and advanced plaques compared to control arteries and in cell
      free serum of patients with high-grade carotid stenosis compared to healthy
      volunteers. In contrast, no differences in DNA methylation were observed in blood
      cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic
      plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA
      demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone
      and DNA methylation and expression of some corresponding methyltransferases are
      significantly altered in atherosclerosis, suggesting a possible contribution of
      epigenetics in disease development. 

PMID- 25993997
TI  - Impact of Elevated D-Dimer on Diagnosis of Acute Aortic Dissection With Isolated
      Neurological Symptoms in Ischemic Stroke.
AB  - BACKGROUND: Plasma D-dimer is known to be a useful clinical marker of
      thrombogenic status, and D-dimer is used as a diagnostic marker for acute aortic
      dissection (AAD). Little is known, however, regarding the clinical value of D
      dimer for diagnosis of asymptomatic AAD in patients with ischemic stroke. We
      investigated whether D-dimer could be used for early diagnosis of AAD with
      isolated neurological symptoms in ischemic stroke patients. METHODS AND RESULTS:
      We evaluated a total of 1,236 consecutive patients with symptomatic ischemic
      stroke without chest or back pain who underwent either head computed tomography
      or magnetic resonance imaging. D-dimer was measured within 24 h after onset.
      There were 9 patients with Stanford type A AAD and they had significantly higher
      D-dimer than the patients without AAD (mean, 46.47+/-54.48 MUg/ml; range, 6.9
      167.1 MUg/ml vs. 2.33+/-3.58 MUg/ml, 0.3-57.9 MUg/ml, P<0.001). When a cut-off of
      6.9 MUg/ml was adopted for d-dimer on the basis of receiver operating
      characteristics analysis, the sensitivity and specificity for AAD were 100% and
      94.8%, respectively, while the positive and negative predictive values were 14.7%
      and 100%, respectively. CONCLUSIONS: D-dimer might be a useful marker for the
      early diagnosis of AAD with isolated neurological symptoms in ischemic stroke
      patients. Whole-body contrast-enhanced computed tomography should be performed in
      ischemic stroke patients who have high D-dimer.

PMID- 25993998
TI  - Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological
      Angiogenesis of Macular Degeneration in Mice.
AB  - Excessive angiogenesis contributes to numerous diseases, including cancer and
      blinding retinopathy. Antibodies against vascular endothelial growth factor
      (VEGF) have been approved and are widely used in clinical treatment. Our previous
      studies using SRPIN340, a small molecule inhibitor of SRPK1 (serine-arginine
      protein kinase 1), demonstrated that SRPK1 is a potential target for the
      development of antiangiogenic drugs. In this study, we solved the structure of
      SRPK1 bound to SRPIN340 by X-ray crystallography. Using pharmacophore docking
      models followed by in vitro kinase assays, we screened a large-scale chemical
      library, and thus identified a new inhibitor of SRPK1. This inhibitor, SRPIN803,
      prevented VEGF production more effectively than SRPIN340 owing to the dual
      inhibition of SRPK1 and CK2 (casein kinase 2). In a mouse model of age-related
      macular degeneration, topical administration of eye ointment containing SRPIN803
      significantly inhibited choroidal neovascularization, suggesting a clinical
      potential of SRPIN803 as a topical ointment for ocular neovascularization. Thus
      SRPIN803 merits further investigation as a novel inhibitor of VEGF. 

PMID- 25994000
TI  - A Novel Method for Quantifying Smooth Regional Variations in Myocardial
      Contractility Within an Infarcted Human Left Ventricle Based on Delay-Enhanced
      Magnetic Resonance Imaging.
AB  - Heart failure is increasing at an alarming rate, making it a worldwide epidemic.
      As the population ages and life expectancy increases, this trend is not likely to
      change. Myocardial infarction (MI)-induced adverse left ventricular (LV)
      remodeling is responsible for nearly 70% of heart failure cases. The adverse
      remodeling process involves an extension of the border zone (BZ) adjacent to an
      MI, which is normally perfused but shows myofiber contractile dysfunction. To
      improve patient-specific modeling of cardiac mechanics, we sought to create a
      finite element model of the human LV with BZ and MI morphologies integrated
      directly from delayed-enhancement magnetic resonance (DE-MR) images. Instead of
      separating the LV into discrete regions (e.g., the MI, BZ, and remote regions)
      with each having a homogeneous myocardial material property, we assumed a
      functional relation between the DE-MR image pixel intensity and myocardial
      stiffness and contractility--we considered a linear variation of material
      properties as a function of DE-MR image pixel intensity, which is known to
      improve the accuracy of the model's response. The finite element model was then
      calibrated using measurements obtained from the same patient--namely, 3D strain
      measurements-using complementary spatial modulation of magnetization magnetic
      resonance (CSPAMM-MR) images. This led to an average circumferential strain error
      of 8.9% across all American Heart Association (AHA) segments. We demonstrate the
      utility of our method for quantifying smooth regional variations in myocardial
      contractility using cardiac DE-MR and CSPAMM-MR images acquired from a 78-yr-old
      woman who experienced an MI approximately 1 yr prior. We found a remote
      myocardial diastolic stiffness of C(0) = 0.102 kPa, and a remote myocardial
      contractility of T(max) = 146.9 kPa, which are both in the range of previously
      published normal human values. Moreover, we found a normalized pixel intensity
      range of 30% for the BZ, which is consistent with the literature. Based on these
      regional myocardial material properties, we used our finite element model to
      compute patient-specific diastolic and systolic LV myofiber stress distributions,
      which cannot be measured directly. One of the main driving forces for adverse LV
      remodeling is assumed to be an abnormally high level of ventricular wall stress,
      and many existing and new treatments for heart failure fundamentally attempt to
      normalize LV wall stress. Thus, our noninvasive method for estimating smooth
      regional variations in myocardial contractility should be valuable for optimizing
      new surgical or medical strategies to limit the chronic evolution from infarction
      to heart failure.

PMID- 25993999
TI  - Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental
      Acute Pancreatitis in Mice.
AB  - Acute pancreatitis (AP) is an inflammatory disease, and is one of the most common
      gastrointestinal disorders worldwide. Soluble epoxide hydrolase (sEH; encoded by
      Ephx2) deficiency and pharmacological inhibition have beneficial effects in
      inflammatory diseases. Ephx2 whole-body deficiency mitigates experimental AP in
      mice, but the suitability of sEH pharmacological inhibition for treating AP
      remains to be determined. We investigated the effects of sEH pharmacological
      inhibition on cerulein- and arginine-induced AP using the selective sEH inhibitor
      1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which was
      administered before and after induction of pancreatitis. Serum amylase and lipase
      levels were lower in TPPU-treated mice compared with controls. In addition,
      circulating levels and pancreatic mRNA of the inflammatory cytokines tumor
      necrosis factor-alpha, interleukin Il-1beta, and Il-6 were reduced in TPPU
      treated mice. Moreover, sEH pharmacological inhibition before and after induction
      of pancreatitis was associated with decreased cerulein- and arginine-induced
      nuclear factor-kappaB inflammatory response, endoplasmic reticulum stress, and
      cell death. sEH pharmacological inhibition before and after induction of
      pancreatitis mitigated cerulein- and arginine-induced AP. This work suggests that
      sEH pharmacological inhibition may be of therapeutic value in acute pancreatitis.

PMID- 25994001
TI  - Occurrence of thyroxine tablet (Thyradin S((r))) - induced liver dysfunction in a
      patient with subclinical hypothyroidism.
AB  - A 54-year-old woman with subclinical hypothyroidism developed liver dysfunction
      after increasing dose of levothyroxine (L-T4) in tablet form (Thyradin S((r)))
      from 25MUg to 50MUg. Viral hepatitis, autoimmune hepatitis and NASH were ruled
      out with examinations. After cessation of levothyroxine in 50MUg tablet form,
      liver enzymes gradually returned to normal. She was diagnosed levothyroxine
      induced liver injury, based on criteria proposed in DDW-J 2004 workshop. Thyradin
      S((r)) powder 0.01% (here in after referred to as L-T4 in powder form) was tried
      as an alternative, and liver enzymes have remained within normal range. As for
      Thyradin S((r)) tablet, additives are different for each type of levothyroxine
      sodium content. The difference of additive is whether Fe2O3 is contained or not:
      it is not included in Thyradin S((r)) 50MUg tablet and powder form. Although
      there are two case reports in the Japanese literature and three case reports in
      the English literature of liver dysfunction suspected due to L-T4, we cannot find
      past reports about cases of drug induced liver dysfunction due to Fe2O3 free
      levothyroxine tablet form. This is a rare case report of drug induced liver
      injury due to Fe2O3 free levothyroxine tablet form, and administration of L-T4 in
      powder form may be useful for treatment of cases similar to this one. 

PMID- 25994002
TI  - Use of antibiotics in paediatric primary care settings in Serbia.
AB  - OBJECTIVE: The aim of the study was to compare the quality of antibiotic use
      among children in primary settings with the internationally developed disease
      specific quality indicators and with National Guidelines. DESIGN: Prescriptions
      of systemic antibiotics to the paediatric population (<18 years) at the primary
      level of healthcare for the period between 2011 and 2013 were analysed by using
      the National Health Insurance Fund's outpatient reimbursement database. RESULTS:
      The mean annual number of antibiotic prescriptions was 1.887.615, while the mean
      annual number of children receiving antibiotics was 728.285. The prescription
      rate slightly decreased by 10% from 1.516 antibiotic prescriptions per 1000
      persons per year in 2011 to 1.365 in 2013. The highest percentage of prescribed
      antibiotics was observed in the group of children aged 2-23 months. The mean
      annual prevalence of antibiotic prescriptions was 54%. The percentage of patients
      prescribed an antibiotic for acute upper respiratory tract infections, acute
      tonsillitis and acute otitis media (AOM) was above the proposed range (<= 20),
      87% -96%. These three diagnoses represent more than 69% of all indications for
      prescribing antibiotics. The percentage of patients prescribed a recommended
      antibiotic was below the proposed range (>= 80%), 1% -17%, while the adherence
      rate to National Guidelines was low, 19%-28%. The percentage of patients
      prescribed quinolones was above the proposed range for AOM (<= 5%), 7%. There
      were no significant differences in indicators value at the regional level in
      Serbia. CONCLUSIONS: Antibiotic use among children in Serbia is extremely high
      compared with that in most other European countries. Major problems are frequent
      use of antibiotics for indications that usually receive no benefit from this
      treatment and the use of broad-spectrum antibiotics.

PMID- 25994003
TI  - Question 2: Should 0.9% saline be used for maintenance fluids in hospitalised
      children?

PMID- 25994004
TI  - Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse
      pancreatic beta-cells.
AB  - Glucose activates the glucose-sensing receptor T1R3 and facilitates its own
      metabolism in pancreatic beta-cells. An inhibitor of this receptor would be
      helpful in elucidating the physiological function of the glucose-sensing
      receptor. The present study was conducted to examine whether or not lactisole can
      be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose
      dependent manner, lactisole inhibited insulin secretion induced by sweeteners,
      acesulfame-K, sucralose and glycyrrhizin. The IC50 was ~4 mmol/l. Lactisole
      attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by
      sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP
      concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the
      action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations
      of intracellular [NADH] and intracellular [ATP] induced by glucose, and also
      inhibited glucose-induced insulin secretion. To further examine the effect of
      lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In
      these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated
      the sucralose-induced increase in [Ca2+]c but did not affect the elevation of
      [cAMP]c. Finally, lactisole inhibited insulin secretion induced by a high
      concentration of glucose in mouse islets. These results indicate that the mouse
      glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in
      assessing the role of the glucose-sensing receptor in mouse pancreatic beta
      cells.

PMID- 25994005
TI  - Milk-soluble formula increases food intake and reduces Il6 expression in elderly
      rat hypothalami.
AB  - Malnutrition in the elderly is accompanied by several metabolic dysfunctions,
      especially alterations in energy homeostasis regulation and a loss of insulin
      responsiveness. Nutritional recommendations aim to enrich food with high protein
      and energy supplements, and protein composition and lipid quality have been
      widely studied. Despite the numerous studies that have examined attempts to
      overcome malnutrition in the elderly through such nutritional supplementation, it
      is still necessary to study the effects of a combination of protein, lipids, and
      vitamin D (VitD). This can be done in animal models of elderly malnutrition. In
      the present study, we investigated the effects of several diet formulae on
      insulin responsiveness, inflammation, and the hypothalamic expression of key
      genes that are involved in energy homeostasis control. To mimic elderly
      malnutrition in humans, elderly Wistar rats were food restricted (R, -50%) for 12
      weeks and then refed for 4 weeks with one of four different isocaloric diets: a
      control diet; a diet where milk soluble protein (MSP) replaced casein; a blend of
      milk fat, rapeseed, and DHA (MRD); or a full formula (FF) diet that combined MSP
      and a blend of MRD (FF). All of the refeeding diets contained VitD. We concluded
      that: (i) food restriction led to the upregulation of insulin receptor in liver
      and adipose tissue accompanied by increased Tnfalpha in the hypothalamus; (ii) in
      all of the refed groups, refeeding led to similar body weight gain during the
      refeeding period; and (iii) refeeding with MSP and MRD diets induced higher food
      intake on the fourth week of refeeding, and this increase was associated with
      reduced hypothalamic interleukin 6 expression.

PMID- 25994007
TI  - Over-expression of recombinant proteins with N-terminal His-tag via subcellular
      uneven distribution in Escherichia coli.
AB  - Specific tags with defined amino acid residues are widely used to purify or probe
      target proteins. Interestingly, the tagging system occasionally results in an
      increase of the recombinant protein expression in vivo. Here, we systematically
      examined this phenomenon using a poly-histidine (His)-tag fused to N- or C
      terminal region of green, red, and blue fluorescent proteins by quantification
      and uneven distribution in cytoplasm of Escherichia coli. This effect was further
      supported by the distinct over-expression of several unrelated proteins, such as
      esterase, neopullulanase, and chloramphenicol acetyltransferase, tagging with the
      same tag. These results suggest that a poly-His-tag placed at N-terminal region
      can induce over-expression of recombinant protein via subcellular uneven
      distribution in vivo. 

PMID- 25994008
TI  - Differential expression of bone morphogenetic protein 5 in human lung squamous
      cell carcinoma and adenocarcinoma.
AB  - Bone morphogenetic proteins (BMPs) play important roles in tumor cell
      proliferation, metastasis, and invasion. However, the expression patterns of BMPs
      in patients with non-small-cell lung cancer (NSCLC) and their correlations with
      NSCLC pathogenesis have not been examined yet. In this study, the mRNA levels of
      BMP family members in NSCLC tissues were analyzed and results showed that the
      mRNA levels of BMP5 and BMP7 were significantly down-regulated and up-regulated,
      respectively, in tumor tissues compared with those in the corresponding
      noncancerous tissues. Interestingly, the mRNA level of BMP5 was significantly
      higher in lung adenocarcinoma tissues than that in lung squamous cell carcinoma
      tissues. Furthermore, results from immunohistochemistry analysis confirmed
      stronger expression of BMP5 protein in lung adenocarcinoma than in lung squamous
      cell carcinoma. Our findings suggested that BMP5 might be a potential prognostic
      biomarker or therapeutic target for patients with NSCLC. 

PMID- 25994006
TI  - 60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus:
      the neuroanatomical legacy of Geoffrey Harris.
AB  - In November 1955, Geoffrey Harris published a paper based on the Christian A
      Herter Lecture he had given earlier that year at Johns Hopkins University in
      Baltimore, MD, USA. The paper reviewed the contemporary research that was
      starting to explain how the hypothalamus controlled the pituitary gland. In the
      process of doing so, Harris introduced a set of properties that helped define the
      neuroendocrine hypothalamus. They included: i) three criteria that putative
      releasing factors for adenohypophysial hormones would have to fulfill; ii) an
      analogy between the representation of body parts in the sensory and motor
      cortices and the spatial localization of neuroendocrine function in the
      hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and
      the pituitary stalk functions as a Sherringtonian final common pathway through
      which the impact of sensory and emotional events on neuroendocrine neurons must
      pass in order to control pituitary hormone release. Were these properties a sign
      that the major neuroscientific discoveries that were being made in the early
      1950s were beginning to influence neuroendocrinology? This Thematic Review
      discusses two main points: the context and significance of Harris's Herter
      Lecture for how our understanding of neuroendocrine anatomy (particularly as it
      relates to the control of the adenohypophysis) has developed since 1955; and,
      within this framework, how novel and powerful techniques are currently taking our
      understanding of the structure of the neuroendocrine hypothalamus to new levels. 

PMID- 25994009
TI  - Not so colourful after all: eggshell pigments constrain avian eggshell colour
      space.
AB  - Birds' eggshells are renowned for their striking colours and varied patterns.
      Although often considered exceptionally diverse, we report that avian eggshell
      coloration, sampled here across the full phylogenetic diversity of birds,
      occupies only 0.08-0.10% of the avian perceivable colour space. The
      concentrations of the two known tetrapyrrole eggshell pigments (protoporphyrin
      and biliverdin) are generally poor predictors of colour, both intra- and
      interspecifically. Here, we show that the constrained diversity of eggshell
      coloration can be accurately predicted by colour mixing models based on the
      relative contribution of both pigments and we demonstrate that the models'
      predictions can be improved by accounting for the reflectance of the eggshell's
      calcium carbonate matrix. The establishment of these proximate links between
      pigmentation and colour will enable future tests of hypotheses on the functions
      of perceived avian eggshell colours that depend on eggshell chemistry. More
      generally, colour mixing models are not limited to avian eggshell colours but
      apply to any natural colour. Our approach illustrates how modelling can aid the
      understanding of constraints on phenotypic diversity. 

PMID- 25994010
TI  - Host age modulates within-host parasite competition.
AB  - In many host populations, one of the most striking differences among hosts is
      their age. While parasite prevalence differences in relation to host age are well
      known, little is known on how host age impacts ecological and evolutionary
      dynamics of diseases. Using two clones of the water flea Daphnia magna and two
      clones of its bacterial parasite Pasteuria ramosa, we examined how host age at
      exposure influences within-host parasite competition and virulence. We found that
      multiply-exposed hosts were more susceptible to infection and suffered higher
      mortality than singly-exposed hosts. Hosts oldest at exposure were least often
      infected and vice versa. Furthermore, we found that in young multiply-exposed
      hosts competition was weak, allowing coexistence and transmission of both
      parasite clones, whereas in older multiply-exposed hosts competitive exclusion
      was observed. Thus, age-dependent parasite exposure and host demography (age
      structure) could together play an important role in mediating parasite evolution.
      At the individual level, our results demonstrate a previously unnoticed
      interaction of the host's immune system with host age, suggesting that the
      specificity of immune function changes as hosts mature. Therefore, evolutionary
      models of parasite virulence might benefit from incorporating age-dependent
      epidemiological parameters. 

PMID- 25994011
TI  - Does dishonesty really invite third-party punishment? Results of a more stringent
      test.
AB  - Many experiments have demonstrated that people are willing to incur cost to
      punish norm violators even when they are not directly harmed by the violation.
      Such altruistic third-party punishment is often considered an evolutionary
      underpinning of large-scale human cooperation. However, some scholars argue that
      previously demonstrated altruistic third-party punishment against fairness-norm
      violations may be an experimental artefact. For example, envy-driven retaliatory
      behaviour (i.e. spite) towards better-off unfair game players may be
      misidentified as altruistic punishment. Indeed, a recent experiment demonstrated
      that participants ceased to inflict third-party punishment against an unfair
      player once a series of key methodological problems were systematically
      controlled for. Noticing that a previous finding regarding apparently altruistic
      third-party punishment against honesty-norm violations may have been subject to
      methodological issues, we used a different and what we consider to be a more
      sound design to evaluate these findings. Third-party punishment against dishonest
      players withstood this more stringent test. 

PMID- 25994012
TI  - Basal blood glucose concentration in free-living striped mice is influenced by
      food availability, ambient temperature and social tactic.
AB  - Vertebrates obtain most of their energy through food, which they store mainly as
      body fat or glycogen, with glucose being the main energy source circulating in
      the blood. Basal blood glucose concentration (bBGC) is expected to remain in a
      narrow homeostatic range. We studied the extent to which bBGC in free-living
      African striped mice (Rhabdomys pumilio) is influenced by ecological factors with
      a bearing on energy regulation, i.e. food availability, abiotic environmental
      variation and social tactic. Striped mice typically form extended family groups
      that huddle together at night, reducing energetic costs of thermoregulation, but
      solitary individuals also occur in the population. We analysed 2827 blood samples
      from 1008 individuals of seven different social categories that experienced
      considerable variation in food supply and abiotic condition. Blood samples were
      taken from mice in the morning after the overnight fast and before foraging. bBGC
      increased significantly with food plant abundance and decreased significantly
      with minimum daily ambient temperature. Solitary striped mice had significantly
      higher bBGC than group-living striped mice. Our results suggest that adaptive
      responses of bBGC occur and we found large natural variation, indicating that
      bBGC spans a far greater homeostatic range than previously thought. 

PMID- 25994013
TI  - Atrial fibrillation (chronic).
AB  - INTRODUCTION: Atrial fibrillation is a supraventricular tachyarrhythmia
      characterised by the presence of fast and uncoordinated atrial activation leading
      to reduced atrial mechanical function. Risk factors for atrial fibrillation
      include increasing age, male sex, co-existing cardiac and thyroid disease,
      pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.
      METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
      following clinical question: What are the effects of oral medical treatments to
      control heart rate in people with chronic (defined as longer than 1 week for this
      review) non-valvular atrial fibrillation? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to May 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
      four 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: beta-blockers (rate-limiting, with or without digoxin), calcium
      channel blockers (with or without digoxin), and digoxin.

PMID- 25994014
TI  - Pharmacotherapy for inherited arrhythmia syndromes: mechanistic basis, clinical
      trial evidence and practical application.
AB  - In the absence of structural heart disease, sudden cardiac death is frequently
      caused by inherited arrhythmia syndromes, such as long QT syndrome, Brugada
      syndrome and catecholaminergic polymorphic ventricular tachycardia. Managing
      these conditions often requires a combination of lifestyle modification,
      pharmacotherapy and less frequently, invasive therapy. Over the past decade,
      patient management has been greatly enhanced by tailored pharmacotherapy as a
      result of a deeper appreciation for arrhythmia mechanisms and supportive evidence
      from multicenter cohort studies. This article reviews current knowledge regarding
      drug therapy for inherited arrhythmias. Anti-arrhythmic mechanisms and available
      clinical evidence are highlighted while maintaining a practical perspective on
      patient management. 

PMID- 25994015
TI  - Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera
      containing nanodisks promote targeted bioactive agent delivery to CD20-positive
      lymphomas.
AB  - A fusion protein comprising an alpha-CD20 single chain variable fragment (scFv)
      antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed
      and expressed in Escherichia coli. The lipid interaction properties intrinsic to
      apoA-I as well as the antigen recognition properties of the scFv were retained by
      the chimera. scFv*apoA-I was formulated into nanoscale reconstituted high-density
      lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells.
      alpha-CD20 scFv*apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL)
      cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat).
      Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a
      monoclonal antibody directed against CD20. Confocal fluorescence microscopy
      analysis of Granta cells following incubation with alpha-CD20 scFv*apoA-I ND
      formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin,
      revealed alpha-CD20 scFv*apoA-I localizes to the cell surface, while curcumin off
      loads and gains entry to the cell. Compared to control incubations, viability of
      cultured NHL cells was decreased upon incubation with alpha-CD20 scFv*apoA-I ND
      harboring curcumin. Thus, formulation of curcumin ND with alpha-CD20 scFv*apoA-I
      as the scaffold component confers cell targeting and enhanced bioactive agent
      delivery, providing a strategy to minimize toxicity associated with
      chemotherapeutic agents. 

PMID- 25994016
TI  - Increasing corticospinal excitability in the antagonist muscle during muscle
      relaxation with a tracking task.
AB  - The present study aimed to investigate corticospinal excitability changes during
      muscle relaxation with a tracking task. The motor-evoked potential, which was
      elicited from the flexor carpi radialis (agonist) and extensor carpi radialis
      (antagonist) muscles, was analyzed in terms of both the relaxation velocity and
      phase. Our results suggest that increasing corticospinal excitability in the
      antagonist muscle plays an important role in controlling the relaxation of the
      agonist muscle during gradual relaxation with a tracking task. 

PMID- 25994017
TI  - Influence of ejaculation frequency on seminal parameters.
AB  - BACKGROUND: Several factors have been shown to influence semen parameters, one of
      which is sexual abstinence; a clinical criteria included in the semen evaluation
      to provide maximum sperm quality. The aim of the present study was to assess the
      effect of a daily ejaculation frequency on conventional and functional semen
      parameters. METHODS: Semen samples were collected daily over a period of two
      weeks of which every second sample per person was processed and analyzed
      according to the World Health Organization guidelines. Furthermore, mitochondrial
      function, intracellular reactive oxygen species production and sperm DNA
      fragmentation were evaluated by flow cytometry. RESULTS: Total sperm count and
      seminal volume per ejaculation declined and remained decreased for the duration
      of the daily ejaculation period. However, conventional parameters such as sperm
      concentration, motility, progressive motility, morphology, vitality and
      functional parameters such as sperm plasma membrane integrity, mitochondrial
      membrane potential and DNA fragmentation was not significantly affected and
      remained similar to the initial measurement throughout the daily ejaculation
      period. Despite intra- and inter individual variations, the average values of the
      basic semen parameters remained above the WHO (2010) reference values throughout
      the daily ejaculation period. Interestingly, a decreasing trend in intracellular
      ROS production was observed, although statistically not significant. CONCLUSIONS:
      The study shows that an extended 2 week period of daily ejaculation does not have
      major clinical effects on conventional and functional seminal parameters.

PMID- 25994019
TI  - Re-experiencing traumatic events in PTSD: new avenues in research on intrusive
      memories and flashbacks.
AB  - Posttraumatic flashbacks, consisting of the intrusive re-experiencing of
      traumatic experiences in the present, have been more clearly defined for the
      first time in DSM-5 and have been identified as a unique symptom of posttraumatic
      stress disorder in the proposed ICD-11 diagnostic criteria. Relatively little
      research into flashbacks has been conducted, however, and new research efforts
      are required to understand the cognitive and biological basis of this important
      symptom. In addition, there is considerable scope for research into how
      flashbacks should be assessed and into flashbacks occurring in different
      contexts, such as psychosis or intensive care. 

PMID- 25994020
TI  - Prolonged grief: setting the research agenda.
AB  - BACKGROUND: Prolonged grief disorder is proposed for the International
      Classification of Diseases (ICD-11), though it was rejected as a diagnosis for
      DSM-5. OBJECTIVE: This review outlines findings and defines important areas for
      future research viewed from a lifespan perspective. RESULTS: The development and
      psychometric evaluation of measures for the new diagnosis is paramount,
      specifically for children and adolescents. Treatments need to be adapted for
      specific subgroups and research findings have to be disseminated into various
      professional settings.

PMID- 25994018
TI  - Intra-tumor genetic heterogeneity and alternative driver genetic alterations in
      breast cancers with heterogeneous HER2 gene amplification.
AB  - BACKGROUND: HER2 is overexpressed and amplified in approximately 15% of invasive
      breast cancers, and is the molecular target and predictive marker of response to
      anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2
      gene amplification can be found, which creates clinically challenging scenarios.
      Currently, breast cancers with HER2 amplification/overexpression in just over 10%
      of cancer cells are considered HER2-positive for clinical purposes; however, it
      is unclear as to whether the HER2-negative components of such tumors would be
      driven by distinct genetic alterations. Here we sought to characterize the
      pathologic and genetic features of the HER2-positive and HER2-negative components
      of breast cancers with heterogeneous HER2 gene amplification and to define the
      repertoire of potential driver genetic alterations in the HER2-negative
      components of these cases. RESULTS: We separately analyzed the HER2-negative and
      HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy
      number profiling and massively parallel sequencing, and identified potential
      driver genetic alterations restricted to the HER2-negative cells in each case. In
      vitro experiments provided functional evidence to suggest that BRF2 and DSN1
      overexpression/amplification, and the HER2 I767M mutation may be alterations that
      compensate for the lack of HER2 amplification in the HER2-negative components of
      HER2 heterogeneous breast cancers. CONCLUSIONS: Our results indicate that even
      driver genetic alterations, such as HER2 gene amplification, can be
      heterogeneously distributed within a cancer, and that the HER2-negative
      components are likely driven by genetic alterations not present in the HER2
      positive components, including BRF2 and DSN1 amplification and HER2 somatic
      mutations.

PMID- 25994021
TI  - The "one size fits all" approach to trauma treatment: should we be satisfied?
AB  - There have been significant advances in the treatment of posttraumatic stress
      disorder in the last two decades. Further improvements in outcomes will be
      supported by recognition of the heterogeneity of symptoms in trauma populations
      and the development of treatments that promote the tailoring of interventions
      according to patient needs. Collaboration with patients regarding preferences
      about treatment structure, process, and outcomes is critical and will benefit the
      effectiveness and quality of treatments as well as the speed of their
      dissemination. New research methodologies are required that can incorporate
      important variables such as patient preferences and symptom heterogeneity without
      necessarily extending already lengthy study times or further complicating study
      designs. An example of alternative methodology is proposed. 

PMID- 25994022
TI  - Untested assumptions: psychological research and credibility assessment in legal
      decision-making.
AB  - BACKGROUND: Trauma survivors often have to negotiate legal systems such as
      refugee status determination or the criminal justice system. METHODS & RESULTS:
      We outline and discuss the contribution which research on trauma and related
      psychological processes can make to two particular areas of law where complex and
      difficult legal decisions must be made: in claims for refugee and humanitarian
      protection, and in reporting and prosecuting sexual assault in the criminal
      justice system. CONCLUSION: There is a breadth of psychological knowledge that,
      if correctly applied, would limit the inappropriate reliance on assumptions and
      myth in legal decision-making in these settings. Specific recommendations are
      made for further study.

PMID- 25994023
TI  - Complex PTSD: research directions for nosology/assessment, treatment, and public
      health.
AB  - Complex posttraumatic stress disorder (CPTSD) in children and adolescents extends
      beyond the core PTSD symptoms to dysregulation in three psychobiological domains:
      (1) emotion processing, (2) self-organization (including bodily integrity), and
      (3) relational functioning. CPTSD research directions for the next decade and
      beyond are identified in three areas: (1) diagnostic classification (establishing
      the empirical integrity of CPTSD as a distinct form of psychopathology) and
      psychometric assessment [validation and refinement of measures of childhood
      polyvictimization and developmental trauma disorder (DTD)], (2) rigorous
      evaluation and refinement of interventions (and algorithms for their delivery)
      developed or adapted for CPTSD and DTD, and (3) the epidemiology of CPTSD and
      DTD, and their public health and safety impact, across the lifespan and
      intergenerationally, for populations, nations, and cultures. 

PMID- 25994024
TI  - A plea for symptom-based research in psychiatry.
AB  - BACKGROUND: The significant proportion of patients suffering from subthreshold
      diagnoses such as partial posttraumatic stress disorder (PTSD) shows that today's
      diagnostic entities do not fully meet the reality and needs of clinical practice.
      Moreover, as stated also in the recently announced concept of research domain
      criteria (RDoC), the use of today's traditional diagnostic systems in psychiatric
      research does not sufficiently promote an integrative understanding of mental
      disorders across multiple units of analysis from behavior to neurobiology.
      Besides RDoC, core symptom-based research concepts have been proposed to bridge
      the translational gap in psychiatry, but, unfortunately, have not yet become the
      rule. OBJECTIVE/METHOD: First, this article briefly reviews literature on
      subthreshold PTSD (as an example for subthreshold diagnoses) and, second, pleas
      for and proposes a modified symptom-based research concept in psychiatry.
      RESULTS: Subthreshold PTSD has, like other subthreshold psychiatric diagnoses,
      not yet been clearly defined. Diagnostic entities such as subthreshold PTSD are
      subject to a certain arbitrariness as they are mainly the result of empiricism.
      This fact stresses the urgent need for neurobiologically-informed psychiatric
      diagnoses and motivated the here-presented proposal of a symptom-based research
      concept. As proposed here, and before by other researchers, symptom-based
      research in psychiatry should refrain from studying patient cohorts compiled
      according to diagnoses but, instead, should focus on assessing cohorts grouped
      according to chief complaints or predominant psychopathological symptoms.
      CONCLUSIONS: The linkage of the RDoC concept and symptom-based psychiatric
      research might probably speed up the definition of biologically or symptom-based
      psychiatric diagnoses, which might replace the auxiliary constructs of
      "traditional" diagnoses such as full and subthreshold PTSD, and promote the
      development of novel psychological and pharmacological treatments.

PMID- 25994025
TI  - Mobile mental health: a challenging research agenda.
AB  - The field of mobile health ("m-Health") is evolving rapidly and there is an
      explosive growth of psychological tools on the market. Exciting high-tech
      developments may identify symptoms, help individuals manage their own mental
      health, encourage help seeking, and provide both preventive and therapeutic
      interventions. This development has the potential to be an efficient cost
      effective approach reducing waiting lists and serving a considerable portion of
      people globally ("g-Health"). However, few of the mobile applications (apps) have
      been rigorously evaluated. There is little information on how valid screening and
      assessment tools are, which of the mobile intervention apps are effective, or how
      well mobile apps compare to face-to-face treatments. But how feasible is rigorous
      scientific evaluation with the rising demands from policy makers, business
      partners, and users for their quick release? In this paper, developments in m
      Health tools-targeting screening, assessment, prevention, and treatment-are
      reviewed with examples from the field of trauma and posttraumatic stress
      disorder. The academic challenges in developing and evaluating m-Health tools are
      being addressed. Evidence-based guidance is needed on appropriate research
      designs that may overcome some of the public and ethical challenges (e.g.,
      equity, availability) and the market-driven wish to have mobile apps in the "App
      Store" yesterday rather than tomorrow. 

PMID- 25994026
TI  - Trauma-related dissociation and altered states of consciousness: a call for
      clinical, treatment, and neuroscience research.
AB  - The primary aim of this commentary is to describe trauma-related dissociation and
      altered states of consciousness in the context of a four-dimensional model that
      has recently been proposed (Frewen & Lanius, 2015). This model categorizes
      symptoms of trauma-related psychopathology into (1) those that occur within
      normal waking consciousness and (2) those that are dissociative and are
      associated with trauma-related altered states of consciousness (TRASC) along four
      dimensions: (1) time; (2) thought; (3) body; and (4) emotion. Clinical
      applications and future research directions relevant to each dimension are
      discussed. Conceptualizing TRASC across the dimensions of time, thought, body,
      and emotion has transdiagnostic implications for trauma-related disorders
      described in both the Diagnostic Statistical Manual and the International
      Classifications of Diseases. The four-dimensional model provides a framework,
      guided by existing models of dissociation, for future research examining the
      phenomenological, neurobiological, and physiological underpinnings of trauma
      related dissociation. 

PMID- 25994027
TI  - The underlying dimensionality of PTSD in the diagnostic and statistical manual of
      mental disorders: where are we going?
AB  - There has been a substantial body of literature devoted to answering one
      question: Which latent model of posttraumatic stress disorder (PTSD) best
      represents PTSD's underlying dimensionality? This research summary will,
      therefore, focus on the literature pertaining to PTSD's latent structure as
      represented in the fourth (DSM-IV, 1994) to the fifth (DSM-5, 2013) edition of
      the DSM. This article will begin by providing a clear rationale as to why this is
      a pertinent research area, then the body of literature pertaining to the DSM-IV
      and DSM-IV-TR will be summarised, and this will be followed by a summary of the
      literature pertaining to the recently published DSM-5. To conclude, there will be
      a discussion with recommendations for future research directions, namely that
      researchers must investigate the applicability of the new DSM-5 criteria and the
      newly created DSM-5 symptom sets to trauma survivors. In addition, researchers
      must continue to endeavour to identify the "correct" constellations of symptoms
      within symptom sets to ensure that diagnostic algorithms are appropriate and aid
      in the development of targeted treatment approaches and interventions. In
      particular, the newly proposed DSM-5 anhedonia model, externalising behaviours
      model, and hybrid models must be further investigated. It is also important that
      researchers follow up on the idea that a more parsimonious latent structure of
      PTSD may exist. 

PMID- 25994028
TI  - Trauma and PTSD: setting the research agenda.

PMID- 25994029
TI  - An atypical IgM class platelet cold agglutinin induces GPVI-dependent aggregation
      of human platelets.
AB  - Platelet cold agglutinins (PCA) cause pseudothrombocytopenia, spurious
      thrombocytopenia due to ex vivo platelet clumping, complicating clinical
      diagnosis, but mechanisms and consequences of PCA are not well defined. Here, we
      characterised an atypical immunoglobulin (Ig)M PCA in a 37-year-old woman with
      lifelong bleeding and chronic moderate thrombocytopenia, that induces activation
      and aggregation of autologous or allogeneic platelets via interaction with
      platelet glycoprotein (GP)VI. Patient temperature-dependent
      pseudothrombocytopenia was EDTA-independent, but was prevented by integrin
      alphaIIbbeta3 blockade. Unstimulated patient platelets revealed elevated levels
      of bound IgM, increased expression of activation markers (P-selectin and CD63),
      low GPVI levels and abnormally high thromboxane (TX)A2 production. Patient serum
      induced temperature- and alphaIIbbeta3-dependent decrease of platelet count in
      allogeneic donor citrated platelet-rich plasma (PRP), but not in PRP from
      Glanzmann's thrombasthenia or afibrinogenaemia patients. In allogeneic platelets,
      patient plasma induced shape change, P-selectin and CD63 expression, (14)C
      serotonin release, and TXA2 production. Activation was not inhibited by aspirin,
      cangrelor or blocking anti-Fc receptor (FcgammaRIIA) antibody, but was abrogated
      by inhibitors of Src and Syk, and by a soluble GPVI-Fc fusion protein. GPVI
      deficient platelets were not activated by patient plasma. These data provide the
      first evidence for an IgM PCA causing platelet activation/aggregation via GPVI.
      The PCA activity persisted over a five-year follow-up period, supporting a
      causative role in patient chronic thrombocytopenia and bleeding. 

PMID- 25994030
TI  - Association of large intergenic noncoding RNA expression with disease activity
      and organ damage in systemic lupus erythematosus.
AB  - INTRODUCTION: Despite growing evidence that large intergenic noncoding RNAs
      (lincRNAs) can regulate gene expression and widely take part in normal
      physiological and disease conditions, our knowledge of systemic lupus
      erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was
      to detect the levels of four lincRNAs (ENST00000500949: linc0949,
      ENST00000500597: linc0597, ENST00000501992: linc1992, and ENST00000523995:
      linc3995) involved in innate immunity in the peripheral blood mononuclear cells
      (PBMCs) of patients with SLE and correlate these lincRNA levels with disease
      activity, organ damage, clinical features and medical therapies. METHODS: PBMCs
      were obtained from 102 patients with SLE, 54 patients with rheumatoid arthritis
      (RA) and 76 healthy donors. lincRNA expression levels were measured by real-time
      quantitative polymerase chain reaction. Disease activity was assessed using the
      Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, and
      organ damage was evaluated with the Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index. RESULTS: linc0949 and
      linc0597 were significantly decreased in patients with SLE compared with patients
      with RA and healthy control subjects. linc0949 was correlated with SLEDAI-2K
      score (r = -0.329, P = 0.0007), as well as with complement component C3 level (r
      = 0.348, P = 0.0003). The level of linc0949 was also reduced in patients with SLE
      who had the presence of cumulative organ damage. In addition, decreasing
      expression of linc0949 was associated with lupus nephritis. linc0949 expression
      significantly increased after treatment, whereas neither disease activity nor
      organ damage correlated with linc0597 expression. CONCLUSIONS: Our results
      provide novel empirical evidence that linc0949 could be a potential biomarker for
      diagnosis, disease activity and therapeutic response in SLE.

PMID- 25994031
TI  - Identification and Functional Assessment of a New CYP2C9 Allelic Variant
      CYP2C9*59.
AB  - CYP2C9, one of the most important drug-metabolizing enzymes, is responsible for
      metabolizing approximately 15% of clinically important drugs, including warfarin,
      diclofenac, and losartan. Similar to other CYP members, human CYP2C9 exhibits
      marked genetic polymorphisms among individuals of different ethnicities. In this
      study, a novel missense mutation (1300A>T) was identified in a warfarin-sensitive
      patient after a genetic screen of three candidate genes related to high
      variability in response to warfarin doses. This base transversion leads to an Ile
      to-Phe amino acid substitution at codon 434 within the CYP2C9 protein, and this
      new variant has been named a novel allele, CYP2C9*59, by the Human CYP Allele
      Nomenclature Committee (http://www.cypalleles.ki.se/cyp2c9.htm). The exogenous
      expression of CYP2C9.59 in insect cell microsomes revealed that, despite a
      similar protein expression level as wild-type CYP2C9, variant CYP2C9.59 exhibited
      significantly reduced maximal velocity, Vmax, and/or increased Michaelis
      constant, Km, values toward three CYP2C9-specific substrates. Our data suggest
      that the 1300A>T mutation can greatly decrease the enzymatic activity of the
      CYP2C9 protein both in vitro and in vivo. 

PMID- 25994032
TI  - Quantitative Polymerase Chain Reaction Analysis of the Mouse Cyp2j Subfamily:
      Tissue Distribution and Regulation.
AB  - Members of the cytochrome P450 CYP2J subfamily are expressed in multiple tissues
      in mice and humans. These enzymes are active in the metabolism of fatty acids to
      generate bioactive compounds. Herein we report new methods and results for
      quantitative polymerase chain reaction (qPCR) analysis for the seven genes
      (Cyp2j5, Cyp2j6, Cyp2j8, Cyp2j9, Cyp2j11, Cyp2j12, and Cyp2j13) of the mouse
      Cyp2j subfamily. SYBR Green primer sets were developed and compared with
      commercially available TaqMan primer/probe assays for specificity toward mouse
      Cyp2j cDNA, and analysis of tissue distribution and regulation of Cyp2j genes.
      Each TaqMan primer/probe set and SYBR Green primer set were shown to be specific
      for their intended mouse Cyp2j cDNA. Tissue distribution of the mouse Cyp2j
      isoforms confirmed similar patterns of expression between the two qPCR methods.
      Cyp2j5 and Cyp2j13 were highly expressed in male kidneys, and Cyp2j11 was highly
      expressed in both male and female kidneys. Cyp2j6 was expressed in multiple
      tissues, with the highest expression in the small intestine and duodenum. Cyp2j8
      was detected in various tissues, with highest expression found in the skin.
      Cyp2j9 was highly expressed in the brain, liver, and lung. Cyp2j12 was
      predominately expressed in the brain. We also determined the Cyp2j isoform
      expression in Cyp2j5 knockout mice to determine whether there was compensatory
      regulation of other Cyp2j isoforms, and we assessed Cyp2j isoform regulation
      during various inflammatory models, including influenza A, bacterial
      lipopolysaccharide, house dust mite allergen, and corn pollen. Both qPCR methods
      detected similar suppression of Cyp2j6 and Cyp2j9 during inflammation in the
      lung. 

PMID- 25994034
TI  - Visualization of Pulsatile CSF Motion Around Membrane-like Structures with both
      4D Velocity Mapping and Time-SLIP Technique.
AB  - PURPOSE: We compared the depiction of pulsatile CSF motion obtained by 4
      dimensional phase-contrast velocity mapping (4D-VM) with that by time-spatial
      labeling inversion pulse (time-SLIP) technique in the presence of membrane
      structures. MATERIALS AND METHODS: We compared the 2 techniques using a flow
      phantom comprising tubes with and without a thin rubber membrane and applied the
      techniques to 6 healthy volunteers and 2 patients to analyze CSF dynamics
      surrounding thin membrane structures, such as the Liliequist membrane (LM), or
      the wall of an arachnoid cyst. RESULTS: Phantom images exhibited propagation of
      the flow and pressure gradient beyond the membrane in the tube. In contrast,
      fluid labeled by the time-SLIP technique showed little displacement from the
      blockage of spin travelling by the membrane. A similar phenomenon was observed
      around the LM in healthy volunteers and the arachnoid cyst wall in a patient.
      CONCLUSION: Four-dimensional phase-contrast velocity mapping permitted
      visualization of the propagation of CSF pulsation through the intracranial
      membranous structures. This suggests that 4D-VM and the time-SLIP technique
      provide different information on flow and that both techniques are useful for
      classifying the pathophysiological status of CSF and elucidating the propagation
      pathway of CSF pulsation in the cranium.

PMID- 25994035
TI  - Dynamic Blood Oxygen Level-dependent MR Imaging of Muscle: Comparison of
      Postocclusive Reactive Hyperemia in Young Smokers and Nonsmokers.
AB  - PURPOSE: The role of early stage functional assessment of muscle blood flow
      response (MFR) by dynamic muscle blood oxygen level-dependent (BOLD) magnetic
      resonance (MR) imaging is unknown. We investigated the effect of smoking on
      vascular function according to MFR derived from dynamic muscle BOLD MR imaging
      during postocclusive reactive hyperemia in young smokers and nonsmokers. METHODS:
      Sixteen healthy male volunteers (8 smokers, 8 nonsmokers; mean age, 30.4 +/- 4.6
      years) underwent BOLD MR imaging of the left calf muscle. During reactive
      hyperemia provoked by a cuff-compression technique, we measured muscle BOLD (mB)
      using a 3-tesla single-shot multi-echo gradient-echo echo-planar imaging
      sequence. The 2 key mB variables in the reactive hyperemic phase that we studied
      were times to half hyperemic peak (T(1/2peak)) and peak (TTP), each measured from
      cuff deflation. We used the Welch test to assess differences in these between
      smokers and nonsmokers. RESULTS: T(1/2peak) and TTP were significantly longer in
      smokers (P < 0.05) in reactive hyperemia. T(1/2peak) was 13.8 +/- 5.4 s in
      smokers and 7.6 +/- 1.5 s in nonsmokers, and TTP was 67.5 +/- 18.8 s in smokers
      and 45.4 +/- 7.1 s in nonsmokers. CONCLUSION: Dynamic BOLD MR imaging of calf
      muscle during postocclusive reactive hyperemia demonstrated statistically
      significant differences in T(1/2peak) and TTP between young smokers and
      nonsmokers, indicating the presence of early stage smoking-related deterioration
      in MFR.

PMID- 25994036
TI  - Evaluation of Intracranial Dural Arteriovenous Fistulas: Comparison of Unenhanced
      3T 3D Time-of-flight MR Angiography with Digital Subtraction Angiography.
AB  - PURPOSE: We compared gross characterization of intracranial dural arteriovenous
      fistulas (DAVFs) between unenhanced 3-tesla 3-dimensional (3D) time-of-flight
      (TOF) magnetic resonance angiography (MRA) and digital subtraction angiography
      (DSA). METHODS: We subjected 26 consecutive patients with intracranial DAVF to
      unenhanced 3T 3D TOF MRA and to DSA. Two independent sets of observers inspected
      the main arterial feeders, fistula site, and venous drainage pattern on MRA and
      DSA images. Interobserver and intermodality agreements were assessed by k
      statistics. RESULTS: Interobserver agreement was excellent for fistula site
      (kappa = 0.919; 95% confidence interval [CI], 0.805 to 1.000), good for main
      arterial feeders (kappa = 0.711; 95% CI, 0.483 to 0.984), and very good for
      venous drainage (kappa = 0.900; 95% CI, 0.766 to 1.000). Intermodality agreement
      was excellent for fistula site (kappa = 0.968; 95% CI, 0.906 to 1.000) and good
      for main arterial feeder (kappa = 0.809; 95% CI, 0.598 to 1.000) and venous
      drainage (kappa = 0.837; 95% CI, 0.660 to 1.000). CONCLUSION: Gross
      characterization of intracranial DAVF was similar for both imaging modalities,
      but unenhanced 3T 3D TOF MRA cannot replace DSA.

PMID- 25994037
TI  - Impact of the Static and Radiofrequency Magnetic Fields Produced by a 7T MR
      Imager on Metallic Dental Materials.
AB  - PURPOSE: We examined safety issues related to the presence of various metallic
      dental materials in magnetic resonance (MR) imaging at 7 tesla. METHODS: A 7T MR
      imaging scanner was used to examine 18 kinds of materials, including 8 metals
      used in dental restorations, 6 osseointegrated dental implants, 2 abutments for
      dental implants, and 2 magnetic attachment keepers. We assessed translational
      attraction forces between the static magnetic field and materials via deflection
      angles read on a tailor-made instrument and compared with those at 3T. Heating
      effects from radiofrequency during image acquisitions using 6 different sequences
      were examined by measuring associated temperature changes in agarose-gel phantoms
      with a fiber-optic thermometer. RESULTS: Deflection angles of the metallic dental
      materials were significantly larger at 7T than 3T. Among full metal crowns
      (FMCs), deflection angles were 18.0 degrees  for cobalt-chromium (Co-Cr) alloys,
      13.5 degrees  for nickel-chromium (Ni-Cr) alloys, and 0 degrees  for other
      materials. Deflection angles of the dental implants and abutments were minimal,
      ranging from 5.0 to 6.5 degrees , whereas the magnetic attachment keepers were
      strongly attracted to the field, having deflection angles of 90 degrees  or more.
      Increases in temperature of the FMCs were significant but less than 1 degrees C
      in every sequence. The dental implant of 50-mm length showed significant but mild
      temperature increases (up to 1.5 degrees C) when compared with other dental
      implants and abutments, particularly on sequences with high specific absorption
      rate values. CONCLUSION: Although most metallic dental materials showed no
      apparent translational attraction or heating at 7T, substantial attraction forces
      on the magnetic attachment keepers suggested potential risks to patients and
      research participants undergoing MR imaging examinations.

PMID- 25994038
TI  - Validity and Reliability of Magnetic Resonance Elastography for Staging Hepatic
      Fibrosis in Patients with Chronic Hepatitis B.
AB  - PURPOSE: We evaluated the validity and reliability of magnetic resonance
      elastography (MRE) for staging hepatic fibrosis in patients with chronic
      hepatitis B. METHODS: The study included 73 patients with chronic hepatitis B and
      confirmed stages of pathological fibrosis. Two radiologists measured liver
      stiffness using MRE in all cases. We compared the area under the receiver
      operating characteristic (ROC) curve (Az) for distinguishing stages of fibrosis
      compared with MRE liver stiffness measurements and serum fibrosis markers. We
      used intraclass correlation coefficients to analyze interobserver agreement for
      measurements of liver stiffness and 2 one-sided t-tests to test the equivalence
      of the measurements by the 2 observers. RESULTS: ROC analyses revealed the
      significantly superior discrimination abilities of MRE for liver fibrosis staging
      (Az = 0.945 to 0.978 [Observer 1] and 0.936 to 0.967 [Observer 2]) to those of
      serum fibrosis markers (0.491 to 0.742) for both observers (P < 0.0004). The
      intraclass correlation coefficient between the 2 observers was excellent (rho =
      0.971), and the measurements of liver stiffness by the 2 observers were
      statistically equivalent within a 0.1-kPa difference (P = 0.0157)CONCLUSION: MRE
      is a valid and reliable technique for discriminating the stage of hepatic
      fibrosis in patients with chronic hepatitis B.

PMID- 25994039
TI  - Resistance to high-fat diet-induced obesity in male heterozygous Pprc1 knockout
      mice.
AB  - Peroxisome proliferator-activated receptor gamma, co-activator-related 1 (Pprc1)
      is the third member of the Pgc1 family. Other than the well-characterized Pgc1a
      and Pgc1b that act as regulators of mitochondrial biogenesis and oxidative
      metabolism, the function of Pprc1 in vivo is rarely reported, due to embryonic
      lethality of whole-body Pprc1 knockout mice. To investigate the biological and
      physiological function of Pprc1 in metabolic processes, male Pprc1(+/-) mice fed
      with a high fat diet (HFD) showed resistance to diet-induced obesity with a
      decrease of adipose tissue in Pprc1(+/-) mice, which was a result of elevated
      energy expenditure. In skeletal muscle of Pprc1(+/-) mice, Pprc1 level showed
      haplo-insufficiency with down-regulation of Pgc1b and Pgc1a, whereas in adipose
      tissue, Pprc1 expression remained normal, with significant compensatory increase
      of other Pgc1 family members to induce an up-regulation of respiratory chain
      genes. Taken together, as the first report on the metabolic roles of Pprc1 in
      vivo, these results indicated an elevated basal metabolic rate and lipid
      metabolic alteration of male Pprc1(+/-) mice on HFD, suggesting the significant
      role of Pprc1 in controlling mitochondrial gene expression and energy metabolic
      processes, synergistically with Pgc1a and Pgc1b. 

PMID- 25994040
TI  - Distribution of serum immunoglobulin G4 levels in Hashimoto's thyroiditis and
      clinical features of Hashimoto's thyroiditis with elevated serum immunoglobulin
      G4 levels.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is characterized by elevated serum
      IgG4 levels, IgG4-positive plasmacytes, and lymphocyte infiltration into multiple
      organs. IgG4 thyroiditis is a subset of patients with Hashimoto's thyroiditis
      (HT) who exhibited histopathological features of IgG4-RD; its source of serum
      IgG4 is suggested to be the thyroid gland. Although a relationship between IgG4
      RD and IgG4 thyroiditis has been reported, the meaning of serum IgG4 in HT is
      uncertain. In this report, we prospectively evaluated serum IgG4 levels and
      clinical features of patients with HT. A total of 149 patients with HT were
      prospectively recruited into this study. According to the comprehensive
      diagnostic criteria of IgG4-RD, patients were divided into two groups: elevated
      IgG4 (>135 mg/dL) and non-elevated IgG4 (<=135 mg/dL). Median serum IgG4 levels
      of HT patients were 32.0 mg/dL (interquartile range, 20.0-65.0), with a unimodal
      non-normal distribution. Six patients (4.0%) had elevated serum IgG4 levels above
      135 mg/dL. The elevated IgG4 group was older and exhibited enlarged hypoechoic
      areas in the thyroid gland, as revealed by ultrasonography, relative to the non
      elevated IgG4 group. Levothyroxine (L-T4) replacement doses and titers of anti
      thyroid antibodies did not differ significantly between the two groups. Two out
      of six HT patients with elevated serum IgG4 levels had extra-thyroid organ
      involvement as seen in IgG4-RD. In conclusion, HT patients with elevated serum
      IgG4 levels shared clinical features with both IgG4-RD and IgG4 thyroiditis.
      Longer follow-up periods and histopathological assessments are needed to further
      understand the meaning of elevated serum IgG4 levels in HT. 

PMID- 25994041
TI  - Frequency of Migraine Headaches in Patients With Fibromyalgia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the frequency of migraine
      headache in a large cohort of patients with fibromyalgia using a brief migraine
      headache-screening tool. BACKGROUND: Several studies report a high prevalence of
      fibromyalgia among patients with migraine headaches, but there is a dearth of
      research evaluating the frequency of migraine headaches in patients with
      fibromyalgia, despite clinical observations suggesting that migraine headaches
      are common in patients with fibromyalgia. DESIGN AND METHODS: This was a cross
      sectional survey study. Patients (N = 3717) with a previous diagnosis of
      fibromyalgia who were members of the Mayo Clinic Fibromyalgia Registry were
      contacted by electronic survey and asked to complete a brief demographic and
      medical history questionnaire and the validated ID-Migraine screener. RESULTS: A
      total of 1730 patients (46.5%) completed the electronic survey. The majority of
      participants were white (97.2%), female (92.5%), with a mean age of 56.2 (+/
      13.1) years. Of the respondents, 966 (55.8%) met criteria for migraine headaches.
      Hypertension (309 [32.3%] vs. 294 [40.1%], P = .004), asthma (312 [32.5%] vs. 189
      [25.9%], P = .011), irritable bowel syndrome (520 [54.6%] vs. 348 [47.6], P =
      .017), chronic fatigue syndrome (486 [50.7%] vs. 271 [37.1], P < .0001),
      depression (634 [66.5%] vs. 413 [56.7%], P = .0002), anxiety (415 [43.5%] vs. 252
      [34.7%], P = .0011), and post-traumatic stress disorder (172 [18.0%] vs. 96
      [13.2%], P = .006) were all significantly more common in those who met criteria
      for migraine headaches than those who did not. CONCLUSION: The results of this
      study suggest that migraine headaches are common in patients with fibromyalgia.
      Clinicians who care for either population must be aware that these conditions
      commonly overlap and can significantly increase a patient's cumulative disease
      burden.

PMID- 25994042
TI  - Etching holes in graphene supercapacitor electrodes for faster performance.
AB  - Graphene is being widely investigated as a material to replace activated carbon
      in supercapacitor (electrochemical capacitor) electrodes. Supercapacitors have
      much higher energy density, but are typically slow devices (~0.1 Hz) compared to
      other types of capacitors. Here, top-down semiconductor processing has been
      applied to graphene-based electrodes in order to fabricate ordered arrays of
      holes through the graphene electrodes. This is demonstrated to increase the speed
      of the electrodes by reducing the ionic impedance through the electrode
      thickness. This approach may also be applicable to speeding up other types of
      devices, such as batteries and sensors, that use porous electrodes. 

PMID- 25994044
TI  - Understanding the role of iron in the magnetism of Fe doped ZnO nanoparticles.
AB  - The actual role of transition metals like iron in the room temperature
      ferromagnetism (RTFM) of Fe doped ZnO nanoparticles is still an unsolved problem.
      While some studies concluded that the Fe ions participate in the magnetic
      interaction, others in contrast do not believe Fe to play a direct role in the
      magnetic exchange interaction. To contribute to the understanding of this issue,
      we have carefully investigated the structural, optical, vibrational and magnetic
      properties of sol-gel synthesized Zn1-xFexO (0 < x < 0.10) nanoparticles. No
      Fe(2+) was detected in any sample. We found that high spin Fe(3+) ions are
      substitutionally incorporated at the Zn(2+) in the tetrahedral-core sites and in
      pseudo-octahedral surface sites in ZnO. Superficial OH(-) was observed in all
      samples. For x <= 0.03, an increment in Fe doping concentration decreased a and c
      lattice parameters, average Zn-O bond length, average crystallite size and band
      gap; while it increased the degree of distortion and quadrupole splitting.
      Undoped ZnO nanoparticles exhibited very weak RTFM with a saturation
      magnetization (Ms) of ~0.47 memu g(-1) and this value increased to ~2.1 memu g(
      1) for Zn0.99Fe0.01O. Very interestingly, the Ms for Zn0.99Fe0.01O and
      Zn0.97Fe0.03O increased by a factor of about ~2.3 by increasing annealing for 1 h
      to 3 h. For x >= 0.05, ferrimagnetic disordered spinel ZnFe2O4 was formed and
      this phase was found to become more ordered with increasing annealing time. Fe
      does not contribute directly to the RTFM, but its presence promoted the formation
      of additional single charged oxygen vacancies, zinc vacancies, and more oxygen
      ended polar terminations at the nanoparticle surface. These defects, which are
      mainly superficial, altered the electronic structure and are considered as the
      main sources of the observed ferromagnetism. 

PMID- 25994043
TI  - An implementation intention strategy can improve prospective memory in older
      adults with very mild Alzheimer's disease.
AB  - OBJECTIVES: This study tested whether (1) very mild Alzheimer's disease (AD) is
      associated with impaired prospective memory (PM) for tasks that are supported by
      either spontaneous retrieval (focal PM) or strategic monitoring (non-focal PM)
      and (2) implementation intention (II) encoding could improve PM performance in
      very mild AD. DESIGN: Thirty-eight healthy older adults and 34 with very mild AD
      were randomly assigned to perform two PM tasks in either the standard or the II
      encoding condition. METHOD: All participants performed blocks of category
      decision in which they were asked to respond to a focal PM target (e.g., the word
      'orange') and a non-focal PM target (e.g., words that begin with the letter 'o').
      Half of the participants encoded PM instructions in the standard manner, while
      the other half had a stronger encoding by forming IIs. PM accuracy and category
      decision accuracy and reaction times were measured. RESULTS: Participants with
      very mild AD showed deficits in both focal and non-focal PM performance compared
      to the healthy controls, reflecting deficits in both spontaneous retrieval and
      strategic monitoring. Participants with very mild AD in the II encoding condition
      showed better focal PM performance relative to those in the standard encoding
      condition. CONCLUSIONS: Deficits in both focal and non-focal PM are associated
      with very mild AD and IIs may be a helpful behavioural intervention for the focal
      PM deficits. PRACTITIONER POINTS: Multiple deficits in PM are observable in very
      mild AD. Implementation intentions may enhance focal PM in very mild AD. Future
      research using larger samples is needed to better understand the effect of II on
      non-focal PM tasks in healthy older adults and those with very mild AD. The use
      of simple laboratory PM tasks may limit the generality of our findings. Future
      research is needed to investigate whether IIs improve PM over a range of more
      realistic tasks.

PMID- 25994045
TI  - Offload zones to mitigate emergency medical services (EMS) offload delay in the
      emergency department: a process map and hazard analysis.
AB  - Introduction Offload delay is a prolonged interval between ambulance arrival in
      the emergency department (ED) and transfer of patient care, typically occurring
      when EDs are crowded. The offload zone (OZ), which manages ambulance patients
      waiting for an ED bed, has been implemented to mitigate the impact of ED crowding
      on ambulance availability. Little is known about the safety or efficiency. The
      study objectives were to process map the OZ and conduct a hazard analysis to
      identify steps that could compromise patient safety or process efficiency.
      METHODS: A Health Care Failure Mode and Effect Analysis was conducted. Failure
      modes (FM) were identified. For each FM, a probability to occur and severity of
      impact on patient safety and process efficiency was determined, and a hazard
      score (probability X severity) was calculated. For any hazard score considered
      high risk, root causes were identified, and mitigations were sought. RESULTS: The
      OZ consists of six major processes: 1) patient transported by ambulance, 2)
      arrival to the ED, 3) transfer of patient care, 4) patient assessment in OZ, 5)
      patient care in OZ, and 6) patient transfer out of OZ; 78 FM were identified, of
      which 28 (35.9%) were deemed high risk and classified as impact on patient safety
      (n=7/28, 25.0%), process efficiency (n=10/28, 35.7%), or both (n=11/28, 39.3%).
      Seventeen mitigations were suggested. CONCLUSION: This process map and hazard
      analysis is a first step in understanding the safety and efficiency of the OZ.
      The results from this study will inform current policy and practice, and future
      work to reduce offload delay.

PMID- 25994046
TI  - The ketogenic diet in pharmacoresistant childhood epilepsy.
AB  - Available pharmacologic treatments for seizures are limited in their efficacy.
      For a patient with seizures, pharmacologic treatment with available
      anticonvulsant medications leads to seizure control in <70% of patients. Surgical
      resection can lead to control in a select subset of patients but still leaves a
      significant number of patients with uncontrolled seizures. The ketogenic diet and
      related diets have proven to be useful in pharmacoresistant childhood epilepsy. 

PMID- 25994047
TI  - In vitro selenium accessibility in pet foods is affected by diet composition and
      type.
AB  - Se bioavailability in commercial pet foods has been shown to be highly variable.
      The aim of the present study was to identify dietary factors associated with in
      vitro accessibility of Se (Se Aiv) in pet foods. Se Aiv is defined as the
      percentage of Se from the diet that is potentially available for absorption after
      in vitro digestion. Sixty-two diets (dog, n 52; cat, n 10) were in vitro
      enzymatically digested: fifty-four of them were commercially available (kibble, n
      20; pellet, n 8; canned, n 17; raw meat, n 6; steamed meat, n 3) and eight were
      unprocessed (kibble, n 4; canned, n 4) from the same batch as the corresponding
      processed diets. The present investigation examined if Se Aiv was affected by
      diet type, dietary protein, methionine, cysteine, lysine and Se content, DM,
      organic matter and crude protein (CP) digestibility. Se Aiv differed
      significantly among diet types (P< 0.001). Canned and steamed meat diets had a
      lower Se Aiv than pelleted and raw meat diets. Se Aiv correlated positively with
      CP digestibility in extruded diets (kibbles, n 19; r 0.540, P =0.017) and
      negatively in canned diets (n 16; r - 0.611, P =0.012). Moreover, the canning
      process (n 4) decreased Se Aiv (P =0.001), whereas extrusion (n 4) revealed no
      effect on Se Aiv (P =0.297). These differences in Se Aiv between diet types
      warrant quantification of diet type effects on in vivo Se bioavailability. 

PMID- 25994048
TI  - The effect of autologous bone marrow stromal cells differentiated on scaffolds
      for canine tibial bone reconstruction.
AB  - Bone marrow contains mesenchymal stem cells that form many tissues. Various
      scaffolds are available for bone reconstruction by tissue engineering.
      Osteoblastic differentiated bone marrow stromal cells (BMSC) promote osteogenesis
      on scaffolds and stimulate bone regeneration. We investigated the use of cultured
      autologous BMSC on different scaffolds for healing defects in tibias of adult
      male canines. BMSC were isolated from canine humerus bone marrow, differentiated
      into osteoblasts in culture and loaded onto porous ceramic scaffolds including
      hydroxyapatite 1, hydroxyapatite gel and calcium phosphate. Osteoblast
      differentiation was verified by osteonectine and osteocalcine
      immunocytochemistry. The scaffolds with stromal cells were implanted in the
      tibial defect. Scaffolds without stromal cells were used as controls. Sections
      from the defects were processed for histological, ultrastructural,
      immunohistochemical and histomorphometric analyses to analyze the healing of the
      defects. BMSC were spread, allowed to proliferate and differentiate to
      osteoblasts as shown by alizarin red histochemistry, and osteocalcine and
      osteonectine immunostaining. Scanning electron microscopy showed that BMSC on the
      scaffolds were more active and adhesive to the calcium phosphate scaffold
      compared to the others. Macroscopic bone formation was observed in all groups,
      but scaffolds with stromal cells produced significantly better results. Bone
      healing occurred earlier and faster with stromal cells on the calcium phosphate
      scaffold and produced more callus compared to other scaffolds. Tissue healing and
      osteoblastic marker expression also were better with stromal cells on the
      scaffolds. Increased trabecula formation, cell density and decreased fibrosis
      were observed in the calcium phosphate scaffold with stromal cells. Autologous
      cultured stromal cells on the scaffolds were useful for healing of canine tibial
      bone defects. The calcium phosphate scaffold was the best for both cell
      differentiation in vitro and bone regeneration in vivo. It may be possible to
      improve healing of bone defects in humans using stem cells from bone marrow. 

PMID- 25994049
TI  - Multispectroscopic DNA-binding studies of a terbium(III) complex containing 2,2'
      bipyridine ligand.
AB  - Agarose gel electrophoresis, absorption, fluorescence, viscosity, and circular
      dichroism (CD) have been used in exploring the interaction of terbium(III)
      complex, [Tb(bpy)2Cl3(OH2)] where bipy is 2,2'-bipyridine, with Fish salmon DNA.
      Agarose gel electrophoresis assay, along with absorption and fluorescence
      studies, reveal interaction between the corresponding complex and FS-DNA. Also,
      the binding constants (Kb) and the Stern-Volmer quenching constants (Ksv) of
      Tb(III) complex with FS-DNA were determined. The calculated thermodynamic
      parameters suggested that the binding of mentioned complex to FS-DNA was driven
      mainly by hydrophobic interactions. A comparative study of this complex with
      respect to the effect of iodide-induced quenching, ionic strength effect, and
      ethidium bromide exclusion assay reflects binding of explicit to the FS-DNA
      primarily in a groove fashion. CD and viscosity data also support the groove
      binding mode. Furthermore, Tb(III) complex have been simultaneously screened for
      their antibacterial and antifungal activities. 

PMID- 25994050
TI  - Histone deacetylase inhibitors: a review on class-I specific inhibition.
AB  - Histone Deacetylase (HDAC) is an established and validated target for the
      treatment of cancer. It has been attempted to present a comprehensive review on
      the inhibitors for Class-I Histone Deacetylase enzyme family, reported during the
      period from 2002 to 2012. This review has summarized the inhibitors, based on
      their specificity towards different isoforms within this class. Further various
      recent United State (US) patents and the HDAC inhibitors, used singly or in
      combination undergoing clinical trial as anticancer agents have been reviewed.
      Three such inhibitors SAHA, Romidepsin and Belinostat have already been approved
      by the US-FDA for the treatment of cancer.

PMID- 25994051
TI  - Oesophageal cancer: exploring controversies overview of experts' opinions of
      Austria, Germany, France, Netherlands and Switzerland.
AB  - BACKGROUND: Oesophageal carcinoma is a rare disease with often dismal prognosis.
      Despite multiple trials addressing specific issues, currently, many questions in
      management remain unanswered. This work aimed to specifically address areas in
      the management of oesophageal cancer where high level evidence is not available,
      performing trials is very demanding and for many questions high-level evidence
      will not be available in the forseeable future. METHODS: Two experts of each
      national, oesophageal cancer research group from Austria, France, Germany, the
      Netherlands and Switzerland were asked to provide statements to controversial
      issues. After an initial survey, further questions were formulated and answered
      by all experts. The answers were then discussed and qualitatively analysed for
      consensus and controversy. RESULTS: Topics such as indications for PET-CT,
      reasons for induction chemotherapy, radiotherapy dose, the choice of definitive
      chemo-radiotherapy versus surgery in squamous cell cancer, the role of
      radiotherapy in adenocarcinoma and selected surgical issues were identified as
      topics of interest and discussed. CONCLUSION: Areas of significant controversy
      exist in the management of oesophageal cancer, mostly due to high-level evidence.
      This is not expected to change in the upcoming years.

PMID- 25994052
TI  - Transcriptome sequencing and analysis of rubber tree (Hevea brasiliensis Muell.)
      to discover putative genes associated with tapping panel dryness (TPD).
AB  - BACKGROUND: Tapping panel dryness (TPD) involves in the partial or complete
      cessation of latex flow thus seriously affect latex production in rubber tree
      (Hevea brasiliensis). Numerous studies have been conducted to define its origin
      and nature, but the molecular nature and mechanism of TPD occurrence remains
      unknown. This study is committed to de novo sequencing and comparative analysis
      of the transcriptomes of healthy (H) and TPD-affected (T) rubber trees to
      identify the genes and pathways related to the TPD. RESULTS: Total raw reads of
      34,632,012 and 35,913,020 bp were obtained from H and T library, respectively
      using Illumina Hiseq 2000 sequencing technology. De novo assemblies yielded
      141,456 and 169,285 contigs, and 96,070 and 112,243 unigenes from H and T
      library, respectively. Among 73597 genes, 22577 genes were identified as
      differential expressed genes between H and T library via comparative transcript
      profiling. A majority of genes involved in natural rubber biosynthesis and
      jasmonate synthesis with most potential relevance in TPD occurrence were found to
      be differentially expressed. CONCLUSIONS: In TPD-affected trees, the expression
      of most genes related to the latex biosynthesis and jasmonate synthesis was
      severely inhibited and is probably the direct cause of the TPD. These new de novo
      transcriptome data sets provide a significant resource for the discovery of genes
      related to TPD and improve our understanding of the occurrence and maintainace of
      TPD.

PMID- 25994053
TI  - Microvesicles from platelets: novel drivers of vascular inflammation.
AB  - Microvesicles are receiving increased attention not only as biomarkers but also
      as mediators of cell communication and as integral effectors of disease.
      Platelets present a major source of microvesicles and release these microvesicles
      either spontaneously or upon activation. Platelet-derived microvesicles retain
      many features of their parent cells and have been shown to exert modulatory
      effects on vascular and immune cells. Accordingly, microvesicles from platelets
      can be measured at increased levels in patients with cardiovascular disease or
      individuals at risk. In addition, isolated microvesicles from platelets were
      shown to exert immunomodulatory actions on various cell types. In this review the
      various aspects of platelet-derived microvesicles including release, clearance,
      measurement, occurrence during disease and relevance for the pathophysiology of
      vascular inflammation will be discussed. 

PMID- 25994057
TI  - Glycoconjugates, promising subjects for medical science.

PMID- 25994054
TI  - Morphological, cellular and molecular changes during postovulatory egg aging in
      mammals.
AB  - Postovulatory aging is associated with several morphological, cellular and
      molecular changes that deteriorate egg quality either by inducing abortive
      spontaneous egg activation (SEA) or by egg apoptosis. The reduced egg quality
      results in poor fertilization rate, embryo quality and reproductive outcome.
      Although postovulatory aging-induced abortive SEA has been reported in several
      mammalian species, the molecular mechanism(s) underlying this process remains to
      be elucidated. The postovulatory aging-induced morphological and cellular changes
      are characterized by partial cortical granules exocytosis, zona pellucida
      hardening, exit from metaphase-II (M-II)arrest and initiation of extrusion of
      second polar body in aged eggs. The molecular changes include reduction of
      adenosine 3',5'- cyclic monophosphate (cAMP) level, increase of reactive oxygen
      species (ROS) and thereby cytosolic free calcium (Ca(2+)) level. Increased levels
      of cAMP and/or ROS trigger accumulation of Thr-14/Tyr-15 phosphorylated cyclin
      dependent kinase 1 (Cdk1) on one hand and degradation of cyclin B1 through
      ubiquitin-mediated proteolysis on the other hand to destabilize maturation
      promoting factor (MPF). The destabilized MPF triggers postovulatory aging-induced
      abortive SEA and limits various assisted reproductive technologies (ARTs) outcome
      in several mammalian species. Use of certain drugs that can either increase cAMP
      or reduce ROS level would prevent postovulatory aging-induced deterioration in
      egg quality so that more number of good quality eggs can be made available to
      improve ART outcome in mammals including human. 

PMID- 25994058
TI  - Carbohydrate drugs: current status and development prospect.
AB  - In recent years, there has been a great effort devoted to the investigation of
      the roles of carbohydrates in various essential biological processes and the
      development of carbohydrates to therapeutic drugs. This review summarizes the
      carbohydrate drugs which have been recorded in several pharmacopoeias, marketed,
      and under development. A prospect of the future development of carbohydrate drugs
      is discussed as well. 

PMID- 25994056
TI  - Inferring regulatory element landscapes and transcription factor networks from
      cancer methylomes.
AB  - Recent studies indicate that DNA methylation can be used to identify
      transcriptional enhancers, but no systematic approach has been developed for
      genome-wide identification and analysis of enhancers based on DNA methylation. We
      describe ELMER (Enhancer Linking by Methylation/Expression Relationships), an R
      based tool that uses DNA methylation to identify enhancers and correlates
      enhancer state with expression of nearby genes to identify transcriptional
      targets. Transcription factor motif analysis of enhancers is coupled with
      expression analysis of transcription factors to infer upstream regulators. Using
      ELMER, we investigated more than 2,000 tumor samples from The Cancer Genome
      Atlas. We identified networks regulated by known cancer drivers such as GATA3 and
      FOXA1 (breast cancer), SOX17 and FOXA2 (endometrial cancer), and NFE2L2, SOX2,
      and TP63 (squamous cell lung cancer). We also identified novel networks with
      prognostic associations, including RUNX1 in kidney cancer. We propose ELMER as a
      powerful new paradigm for understanding the cis-regulatory interface between
      cancer-associated transcription factors and their functional target genes. 

PMID- 25994059
TI  - Polysaccharides: Candidates of promising vaccine adjuvants.
AB  - Aluminium-based adjuvants remain the only adjuvants approved for human use in the
      USA for over 80 years because of alum's simplicity, tolerability, safety and cost
      efficiency. Recent development of vaccines, especially the increasing
      applications of recombinant subunit and synthetic vaccines, makes aluminium
      adjuvants cannot stimulate enough immunity to the antigens, since aluminium
      adjuvants can only induce Th2 type immune responses. So, novel adjuvants are
      urgent to make up the disadvantages of aluminium adjuvants. However, some major
      hurdles need to be overcome, not only the scientific knowledge of adjuvants but
      also unacceptable side-effects and toxicity. A number of carbohydrate-based
      polysaccharides from plant, bacterial, yeast and synthetic sources can act as
      pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition
      receptors (PRRs) on immune cells, followed by triggering innate immunity and
      regulating adaptive immunity. What is more, polysaccharides are safe and
      biodegradable without tissue deposits as observed in aluminium adjuvants.
      Therefore, polysaccharide-based compounds and formulations are potential vaccine
      adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants
      investigated in recent years. 

PMID- 25994060
TI  - Quality control of sweet medicines based on gas chromatography-mass spectrometry.
AB  - Sweet medicines are a relatively untapped source of new drugs. Their biological
      activities are closely correlated to their chemical characteristics. However,
      accurately defining the chemical characteristics of glycans is a challenge due to
      their chemical heterogeneity and diversity. Gas chromatography-mass spectrometry
      (GC-MS) is an excellent technique for the analysis of glycans even though the
      preparation of adequate derivatives is necessary. We reviewed and discussed the
      most important methodologies currently used for glycan analysis in sweet
      medicines based on GC-MS, including the derivatization for monosaccharide
      analysis, hydrolysis methods for polysaccharide analysis, glycosidic linkage
      analysis based on methylation, and pyrolysis gas chromatography in carbohydrate
      analysis. Finally a strategy for quality control of sweet medicines based on
      quantification analysis is proposed. 

PMID- 25994061
TI  - A novel polysaccharide isolated from Litchi chinensis by using a simulated
      gastric medium and its immunomodulatory activity.
AB  - A novel polysaccharide (LCPA50-S1) with immunomodulatory activity was extracted
      with simulated gastric medium from Litchi chinensis, and purified by DEAE-52
      cellulose column, Sephadex G-50 column and Sephacryl S-300 HR chromatography. The
      structural characteristics of LCPA50-S1 were expounded through complete acid
      hydrolysis, partial acid hydrolysis, methylation and instrumental analysis. The
      results demonstrated that LCPA50-S1 is a heteropolysaccharide with a molecular
      weight of 1.58 * 10(5) Da. The backbone was composed of (1->4)-linked beta-D
      glucopyranosyl residues, (1->6)-linked beta-D-galactopyranosyl, (1->3,6)-linked
      beta-D-galactopyranosyl residues, (1->4,6)-linked alpha-D-glucopyranosyl residues
      and branched at O-6. The branches were consisted of (1->2)-linked alpha-L
      rhamnopyranosyl residues, (1->4)-linked beta-D-glucopyranosyl residues, and (1
      >6)-linked beta-D-galactopyranosyl, terminated with (1->)-linked alpha-L
      arabinopyranosyl residues and (1->)-linked beta-D-galactopyranosyl residues,
      respectively. The immunoregulatory activity of LCPA50-S1 was evaluated through
      determination the effect of LCPA50-S1 on nitric oxide (NO) production of RAW264.7
      macrophages and spleen lymphocyte proliferation as well as its cytokines
      secretion level. The results demonstrated that LCPA50-S1 increased NO and TNF
      alpha production in RAW264.7 macrophages significantly, enhanced the
      proliferation as well as the interleukin-2 (IL-2) production of splenocytes. The
      data indicated that LCPA50-S1 had the potential to be explored as a novel natural
      immunomodulator for application in functional foods and medicine. 

PMID- 25994063
TI  - Galactosylation of caffeic acid by an engineered beta-galactosidase.
AB  - Glycosylation is useful for improving the chemical properties and physiological
      functions of biologically and pharmacologically important compounds. The
      glycosylation of phenolic compounds can increase their solubility and stability
      in water. The addition of galactose residue has special meaning as it facilitates
      targeted delivery of drugs to the liver cancer cells with abundant galactose
      acceptors on the cell surface. In this work, the engineered beta-galactosidase
      W980F from Lactobacillus bulgaricus L3 was utilized for the glycosylation of
      caffeic acid, a well-known phenolic phytochemical with broad bioactivities. The
      reaction was performed by incubation of the enzyme with 200 mM of lactose and 100
      mM of caffeic acid at 45 degrees C for 1 h. The product was purified and analyzed
      by MS and NMR spectra. The MS revealed a signal of [M-H]- at m/z 341.09,
      suggesting monogalactosylated products of caffeic acid (Mr 342). The NMR spectra
      further identified the products to be caffeic acid 3'-O-beta- galactopyranoside
      and caffeic acid 4'-O-beta-galactopyranoside in a ratio of 1:3. This was the
      first discovery that caffeic acid could be galactosylated by the engineered
      glycosidase.

PMID- 25994062
TI  - Structural elucidation and in vitro antioxidant activities of a new
      heteropolysaccharide from Litchi chinensis.
AB  - Two polysaccharides, LCP70S-1 and LCP70W, were isolated from the pulp tissues of
      Litchi chinensis by anion-exchange chromatography and gel-filtration
      chromatography, while the structure of LCP70S-1 was elucidated and its physico
      chemical properties was analyzed. The results demonstrated that LCP70S-1 is
      composed of L-rhamnose, L-arabinose and D-galactose in the ratio of
      1.06:6.39:4.21, and the main chain of the heteropolysaccharide possess (1->3,6)
      linked galactopyranosyl branches at O-6. The three branches consist of (1->3)
      linked rhamnopyranosyl residues, (1->3,6)-linked galactopyranosyl and (1->5)
      linked arabinopyranosyl residues, and terminated with (1->)-linked
      arabinopyranosyl residues, respectively. The two polysaccharides were further
      evaluated with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities
      and their reducing power in vitro. The results showed that LCP70W and LCP70S-1
      possessed significant antioxidant activities, especially for LCP70S-1. As such,
      LCP70S-1 could potentially serve as an antioxidant and would value further study
      for human healthcare. 

PMID- 25994064
TI  - Cancer-associated carbohydrate antigens for clinical diagnostic markers--its
      effectiveness and limitations.
AB  - Cancer cells express various aberrant glycoconjugates. Several kinds of
      carbohydrate antigens have been used for the serological tumor markers. In
      particular, the serological level of sialylated carbohydrate antigens, which
      contain the sialic acid residue in their structure, showed effectiveness in
      diagnosing cancer behavior. Although large number of carbohydrate antigens in
      serum of cancer patients was elevated broadly in various cancers, each tumor
      marker has different sensitivity and specificity for each cancer. Therefore, the
      combined use of several tumor markers which have different characteristics is
      effective for better sensitivity in diagnosing cancer behavior. The mechanism of
      synthesizing cancer-associated carbohydrate antigens is not fully understood
      because it is very complex. In addition, new cancer-associated carbohydrate
      antigens are also identified by molecular oncological studies. Those
      investigations are considered to develop more effective tumor markers to diagnose
      cancer behavior.

PMID- 25994065
TI  - Current use of silkworm larvae (Bombyx mori) as an animal model in pharmaco
      medical research.
AB  - We advocate the use of silkworm larvae, Bombyx mori, as an animal model for
      discovery of drug candidates. We have established several disease models using
      silkworms, which offer technical advantages in drug development and the study of
      host-pathogen interaction. This mini review briefly describes recent trends in
      the use of silkworm larvae as a non-mammalian model for drug discovery and it
      offers suggestions regarding the potential for silkworm use in pharmaceutical
      biomedical research. 

PMID- 25994066
TI  - Comparison and combination effects on antioxidant power of curcumin with gallic
      acid, ascorbic acid, and xanthone.
AB  - Curcumin has been extensively reported as a potential natural antioxidant.
      However, there was no data on activity comparison as well as the biological
      interactions of curcumin with other natural antioxidants. The aim of the present
      study was to investigate the antioxidant power of curcumin in comparison with
      three important natural antioxidants; gallic acid, ascorbic acid, and xanthone on
      free radical scavenging action and their combination effects on this activity.
      The results indicated that the activities of these compounds were dose-dependent.
      The 50% effective concentration (EC50) of curcumin was found to be 11 MUg/mL.
      Curcumin showed significantly higher antioxidant activity than ascorbic acid and
      xanthone but less than gallic acid. Interestingly, curcumin revealed synergistic
      antioxidant effect when combined with gallic acid whereas the antagonistic effect
      occurred in curcumin combination with ascorbic acid or xanthone. These results
      suggest that curcumin-gallic acid combination is the potential antioxidant
      mixture to be used in place of the individual substance whereas using of curcumin
      in combination with ascorbic acid or xanthone should be avoid. 

PMID- 25994067
TI  - Crizotinib-associated erythema multiforme in a lung cancer patient.
AB  - Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine
      kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer
      (NSCLC). A 63-year old woman with postoperative relapsed ALK-positive NSCLC was
      treated with crizotinib. Erythema multiforme (EM) occurred one week after
      initiation of crizotinib therapy. Skin biopsy specimen showed compatible drug
      eruption. The discontinuation of crizotinib improved her eruption within one
      week. This report presented the first case of crizotinib-associated EM, which is
      the preclinical stage of Stevens-Johnson syndrome. Although crizotinib is
      clinically available, we should be aware of its potential severe skin adverse
      event. 

PMID- 25994068
TI  - The study of forensic toxicology should not be neglected in Japanese
      universities.
AB  - Forensic toxicology is aimed at identifying the relationship between drugs or
      poison and the cause of death or crime. In the authors' toxicology laboratory at
      Chiba University, the authors analyze almost every body for drugs and poisons. A
      simple inspection kit was used in an attempt to ascertain drug abuse. A mass
      spectrometer is used to perform highly accurate screening. When a poison is
      detected, quantitative analyses are required. A recent topic of interest is new
      psychoactive substances (NPS). Although NPS-related deaths may be decreasing, use
      of NPS as a cause of death is difficult to ascertain. Forensic institutes have
      recently begun to perform drug and poison tests on corpses. However, this
      approach presents several problems, as are discussed here. The hope is that
      highly accurate analyses of drugs and poisons will be performed throughout the
      country. 

PMID- 25994069
TI  - Non-steroidal anti-inflammatory drugs and their benefits and harms: the challenge
      of interpreting meta-analyses and observational data sets when balanced data are
      not analyzed and reported.
AB  - A multitude of reports have delineated the risks of using non-steroidal anti
      inflammatory drugs but have not been totally congruent. Meta-analyses of
      randomized controlled trials sometimes concur regarding gastrointestinal risk and
      cardiovascular risk but rarely report a balance of these risks for any one drug.
      Benefits measured in these studies are usually not reported. Observational data
      sets, supposedly reflective of 'real world' patients, do not always agree with
      the randomized controlled trial reports. Clinicians need assessments measuring
      the balance of harms and benefits so that better decisions based on their
      patients' unique risk factors can be reached. 

PMID- 25994070
TI  - Drawing Plausible Inferences about the Impact of State Dependent Coverage
      Expansions.

PMID- 25994071
TI  - Young adult dependent coverage: were the state reforms effective? A critique and
      a response.

PMID- 25994072
TI  - The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis:
      a systematic review.
AB  - AIMS/HYPOTHESIS: The use of HbA1c for the diagnosis of diabetes is now widely
      advocated despite caveats to its use. Anaemia is cited as a major confounder to
      this use; however, the effect of erythrocyte indices and to what degree anaemia
      influences HbA1c levels is not known. METHODS: A systematic electronic database
      search of MEDLINE, EMBASE, the Cumulative Index to Nursing & Allied Health
      Literature (CINAHL) and the Cochrane Library was conducted for relevant articles
      published between January 1990 and May 2014. Included studies had at least one
      measurement of HbA1c and glucose, and a least one index of haematinic deficiency,
      involving non-pregnant adults, not known to have diabetes. RESULTS: A total of 12
      articles from 544 were included. The majority of studies focused on iron
      deficiency anaemia (IDA) and, in general, demonstrated that the presence of iron
      deficiency with or without anaemia led to an increase in HbA1c values compared
      with controls, with no concomitant rise in glucose indices. Data on the effects
      of other indices of erythrocyte abnormalities on HbA1c are limited but show a
      possible decrease in HbA1c values with non-iron deficiency forms of anaemia.
      CONCLUSIONS/INTERPRETATION: HbA1c is likely to be affected by iron deficiency and
      IDA with a spurious increase in HbA1c values; conversely, non-IDA may lead to a
      decreased HbA1c value. This may lead to confusion when diagnosing diabetes using
      HbA1c. This review clearly identifies the need for more evidence, especially in
      identifying the types and degrees of anaemia likely to have significant impact on
      the reliability of HbA1c.

PMID- 25994073
TI  - Incretin-based therapies: where will we be 50 years from now?
AB  - The development of incretin-based therapies (glucagon-like peptide 1 [GLP-1]
      receptor agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors) has changed the
      landscape of type 2 diabetes management over the past decade. Current
      developments include longer-acting GLP-1 receptor agonists, fixed-ratio
      combinations of GLP-1 analogues and basal insulin, as well as implantable osmotic
      minipumps for long-term delivery of GLP-1 receptor agonists. In longer terms,
      oral or inhaled GLP-1 analogues may become a reality. In addition, oral enhancers
      of GLP-1 secretion (e.g. via G-protein-coupled receptors, nuclear farnesoid
      receptor X and the G-protein-coupled bile acid-activated receptor [TGR5]) are
      currently being explored in experimental studies. Combination of GLP-1 with other
      gut hormones (e.g. peptide YY, glucagon, gastrin, glucose-dependent
      insulinotropic polypeptide [GIP], secretin, cholecystokinin, vasoactive
      intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide)
      may enhance the glucose- and weight-lowering effect of GLP-1 alone, and dual or
      triple hormone receptor agonists may even exploit the properties of different
      peptides with just one molecule. There is also an increasing interest in
      employing incretin-based therapies in other areas, such as type 1 diabetes,
      impaired glucose metabolism, obesity, polycystic ovary syndrome, non-alcoholic
      fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), psoriasis or
      even neurodegeneration. Thus, incretin-based therapies may continue to broaden
      the therapeutic spectrum for type 2 diabetes and for various other indications in
      the coming years. This is one of a series of commentaries under the banner '50
      years forward', giving personal opinions on future perspectives in diabetes, to
      celebrate the 50th anniversary of Diabetologia (1965-2015).

PMID- 25994074
TI  - GIP increases adipose tissue expression and blood levels of MCP-1 in humans and
      links high energy diets to inflammation: a randomised trial.
AB  - AIMS/HYPOTHESIS: Obesity is associated with elevated monocyte chemoattractant
      protein-1 (MCP-1), a proinflammatory chemokine related to diabetes and
      cardiovascular disease. Since obesity is triggered by energy dense diets, we
      hypothesised that nutrient induced intestinal hormones such as glucose-dependent
      insulinotropic peptide (GIP) may directly stimulate the release of chemokines
      from adipose tissue and induce low-grade inflammation. METHODS: GIP effects on
      gene expression and secretion of inflammatory markers were studied by microarray
      analysis and PCR from human subcutaneous fat biopsies of slightly obese but
      healthy volunteers in the metabolic ward of German Institute of Human Nutrition,
      Department of Clinical Nutrition, Potsdam-Rehbrucke. To allocate the participants
      to the study arms they were numbered in order of their recruitment and then
      assigned to the groups by a random number generator. In a randomised, single
      blind (participants) crossover design, the participants received GIP infusions in
      postprandial concentrations (2 pmol kg(-1) min(-1)) or saline (154 mmol/l NaCl)
      infusions for 240 min either alone, in combination with hyperinsulinaemic
      euglycaemic (EU) or hyperinsulinaemic-hyperglycaemic (HC) clamps. Possible
      mechanisms of GIP effects were investigated in single and co-cultures of
      macrophage and adipocyte cell lines and in primary human monocytes, macrophages
      and adipocytes. RESULTS: A total of 17 participants were randomised to the
      following groups: EU with GIP infusion (n = 9); EU with NaCl infusion (n = 9); HC
      with GIP infusion (n = 8); HC with NaCl infusion (n = 8); sole GIP infusion (n =
      11) and sole placebo infusion (n = 11). All 17 individuals were analysed. The
      study is completed. In human subcutaneous adipose tissue (hSCAT), infusions of
      GIP significantly increased inflammatory chemokine and cytokine gene networks in
      transcriptomic microarray analyses. Particularly MCP-1 (180 +/- 26%), MCP-2 (246
      +/- 58%) and IL-6 (234 +/- 40%) mRNA levels in adipose tissue as well as
      circulating plasma concentrations of MCP-1 (165 +/- 12 vs 135 +/- 13 pg/ml; GIP
      vs saline after 240 min; p < 0.05 for all variables) in humans increased
      independently of circulating insulin or glucose plasma concentrations. GIP
      stimulation increased Mcp-1 mRNA-expression in co-cultures of differentiated
      3T3L1-adipocytes and RAW 264.7 macrophages but not in the isolated cell lines.
      Similarly, GIP increased MCP-1 transcripts in co-cultures of primary human
      macrophages with human adipocytes. GIP receptor (GIPR) transcripts were present
      in primary monocytes and the different cell lines and induced activation of
      extracellular related kinase (ERK) as well as increases in cAMP, indicating
      functional receptors. CONCLUSIONS/INTERPRETATION: Our findings suggest that the
      nutrient induced gut hormone GIP may initiate adipose tissue inflammation by
      triggering a crosstalk of adipocytes and macrophages involving MCP-1. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00774488. FUNDING: This work was supported by
      the German Research Foundation (DFG): grant No. Pf164/021002.

PMID- 25994076
TI  - Erratum to: Analysis of peri-islet CD45-positive leucocytic infiltrates in long
      standing type 1 diabetic patients.

PMID- 25994075
TI  - Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice.
AB  - AIMS/HYPOTHESIS: MicroRNAs (miRs) have been suggested as potential therapeutic
      targets for heart diseases. Inhibition of miR-195 prevents apoptosis in
      cardiomyocytes stimulated with palmitate and transgenic overexpression of miR-195
      induces cardiac hypertrophy and heart failure. We investigated whether silencing
      of miR-195 reduces diabetic cardiomyopathy in a mouse model of streptozotocin
      (STZ)-induced type 1 diabetes. METHODS: Type 1 diabetes was induced in C57BL/6
      mice (male, 2 months old) by injections of STZ. RESULTS: MiR-195 expression was
      increased and levels of its target proteins (B cell leukaemia/lymphoma 2 and
      sirtuin 1) were decreased in STZ-induced type 1 and db/db type 2 diabetic mouse
      hearts. Systemically delivering an anti-miR-195 construct knocked down miR-195
      expression in the heart, reduced caspase-3 activity, decreased oxidative stress,
      attenuated myocardial hypertrophy and improved myocardial function in STZ-induced
      mice with a concurrent upregulation of B cell leukaemia/lymphoma 2 and sirtuin 1.
      Diabetes reduced myocardial capillary density and decreased maximal coronary
      blood flow in mice. Knockdown of miR-195 increased myocardial capillary density
      and improved maximal coronary blood flow in diabetic mice. Upregulation of miR
      195 sufficiently induced apoptosis in cardiomyocytes and attenuated the
      angiogenesis of cardiac endothelial cells in vitro. Furthermore, inhibition of
      miR-195 prevented apoptosis in cardiac endothelial cells in response to NEFA, an
      important feature of diabetes. CONCLUSIONS/INTERPRETATION: Therapeutic silencing
      of miR-195 reduces myocardial hypertrophy and improves coronary blood flow and
      myocardial function in diabetes, at least in part by reducing oxidative damage,
      inhibiting apoptosis and promoting angiogenesis. Thus, miR-195 may represent an
      alternative therapeutic target for diabetic heart diseases.

PMID- 25994077
TI  - Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption.
AB  - Melatonin is an endogenous synchronizer of biological rhythms and a modulator of
      physiological functions and behaviors of all mammals. Reduced levels of melatonin
      and a delay of its nocturnal peak concentration have been found in alcohol
      dependent patients and rats. Here we investigated whether the melatonergic system
      is a novel target to treat alcohol addiction. Male Wistar rats were subjected to
      long-term voluntary alcohol consumption with repeated abstinence phases.
      Circadian drinking rhythmicity and patterns were registered with high temporal
      resolution by a drinkometer system and analyzed by Fourier analysis. We examined
      potential antirelapse effect of the novel antidepressant drug agomelatine. Given
      that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist
      we also tested the effects of melatonin itself and the 5-HT2C antagonist
      SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin
      administered at the end of the light phase led to very similar changes on all
      measures of the post-abstinence drinking behavior, suggesting that effects of
      agomelatine on relapse-like behavior are mostly driven by its melatonergic
      activity. Both drugs caused a clear phase advance in the diurnal drinking pattern
      when compared with the control vehicle-treated group and a reduced frequency of
      approaches to alcohol bottles. Melatonin given at the onset of the light phase
      had no effect on the circadian phase and very small effects on alcohol
      consumption. We conclude that targeting the melatonergic system in alcohol
      dependent individuals can induce a circadian phase advance, which may restore
      normal sleep architecture and reduce relapse behavior. 

PMID- 25994078
TI  - Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates
      Extinction of Drug Seeking After Cocaine Self-Administration.
AB  - Drug exposure results in structural and functional changes in brain regions that
      regulate reward and these changes may underlie the persistence of compulsive drug
      seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor
      (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation,
      and may contribute to these drug-induced changes. Following cocaine exposure,
      bFGF is increased in addiction-related brain regions, including the infralimbic
      medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but
      whether drug-induced overexpression of bFGF in this region affects extinction of
      drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC
      would facilitate extinction following cocaine self-administration. Rats were
      trained to lever press for intravenous infusions of cocaine before extinction.
      Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated
      extinction. In contrast, blocking bFGF alone was not sufficient to facilitate
      extinction, as blocking bFGF and returning rats to their home cage had no effect
      on subsequent extinction. Furthermore, bFGF protein expression increased in IL
      mPFC following cocaine self-administration, an effect reversed by extinction.
      These results suggest that cocaine-induced overexpression of bFGF inhibits
      extinction, as blocking bFGF during extinction permits rapid extinction.
      Therefore, targeted reductions in bFGF during therapeutic interventions could
      enhance treatment outcomes for addiction. 

PMID- 25994079
TI  - Differential uptake of endosulfan in the South American toad under sublethal
      exposure.
AB  - Agroecosystems are usually polluted with a wide variety of contaminants with
      pesticides being very frequently detected. Endosulfan, an organochlorine
      pesticide, has been shown to cause both lethal and sublethal effects on aquatic
      organisms such as amphibians and especially on its early developmental stages. In
      this context, the aim of this study was to evaluate the uptake of environmentally
      relevant concentrations of endosulfan and its correlation with differential
      sensitivity in the early development stages of the common South American toad,
      Rhinella arenarum. Embryos and larvae were exposed to sublethal concentrations of
      endosulfan for several periods of exposures. According to the developmental stage
      at which they were exposed, the uptake rate was different. Bioconcentration
      factors (BCFs) for embryos significantly decreased with exposure time and
      concentration (p < 0.05) reaching a BCF of <=1679 for embryos at 96 h of exposure
      to 0.001 mg endosulfan L(-1). BCFs for larvae significantly increased with
      exposure time (p < 0.05) obtaining a maximum of 40 at 504 h. In our previous
      study, we reported that embryos were less sensitive to the effects of endosulfan
      than larvae, which is in line with the main tendency of embryos to bioconcentrate
      endosulfan as observed in this study.

PMID- 25994080
TI  - A CASE OF BEHCET'S DISEASE AND SYSTEMIC SCLEROSIS DEVELOPING AFTER AN EARTHQUAKE
      DISASTER.
AB  - Stressful life situation can trigger the onset and flare-ups of Behcet's disease
      (BD). In addition, the association of systemic sclerosis (SSc) and BD is rare. In
      this study, we report a patient who had Sjogren's syndrome as a primary disease
      and subsequently developed SSc and BD after an earthquake disaster and the death
      of her father. 

PMID- 25994081
TI  - THE INHIBITORY EFFECT OF PACLITAXEL ON (Kv2.1) K+ CURRENT IN H9c2 CELLS.
AB  - Using the whole-cell voltage clamp technique, we investigated the effect of
      paclitaxel, an anticancer agent which promotes microtubule formation, on K(+)
      current in H9c2 cells originated from rat embryonic cardiac myocytes. Paclitaxel
      inhibited Kv2.1 voltage-dependent K(+) current (IKur) with ultra-rapidly
      activating and slowly inactivating kinetics in a concentration-dependent manner.
      The inhibitory effect of paclitaxel on IKur was time-dependent and more marked at
      200 ms after the onset than at the beginning of the depolarizing pulse. The IC50
      value of paclitaxel was 1.1 uM at 200 ms. The time-dependent inhibition suggests
      that paclitaxel might be an open channel blocker of Kv2.1. This inhibition of
      Kv2.1 may be involved in the adverse effects of paclitaxel on cardiac and
      neuronal cells. 

PMID- 25994083
TI  - Hand washing induces a clean slate effect in moral judgments: a pupillometry and
      eye-tracking study.
AB  - Physical cleansing is commonly understood to protect us against physical
      contamination. However, recent studies showed additional effects on moral
      judgments. Under the heading of the "Macbeth effect" direct links between bodily
      cleansing and one's own moral purity have been demonstrated. Here we investigate
      (1) how moral judgments develop over time and how they are altered by hand
      washing, (2) whether changes in moral judgments can be explained by altered
      information sampling from the environment, and (3) whether hand washing affects
      emotional arousal. Using a pre-post control group design, we found that morality
      ratings of morally good and bad scenes acquired more extreme values in the
      control group over time, an effect that was fully counteracted by intermediate
      hand washing. This result supports the notion of a clean slate effect by hand
      washing. Thereby, eye-tracking data did not uncover differences in eye movement
      behavior that may explain differences in moral judgments. Thus, the clean slate
      effect is not due to altered information sampling from the environment. Finally,
      compared to the control group, pupil diameter decreased after hand washing, thus
      demonstrating a direct physiological effect. The results shed light on the
      physiological mechanisms behind this type of embodiment phenomenon. 

PMID- 25994082
TI  - Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in
      blood samples from patients with inflammatory bowel disease.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive
      Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's
      disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC)
      DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at
      various disease periods and compared against 24 cirrhotic patients with ascites
      (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by
      IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity,
      in selected samples, by sequencing of fimH gene. CD patients with active disease
      showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab
      treatment resulted in decreased MAP detection. CIR patients had high individual
      and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls
      had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC
      DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from
      the selected samples of CD patients analyzed carried the fimH30 allele, with a
      mutation strongly associated with AIEC. Our results show that coinfection with
      MAP and AIEC is common and persistent in CD, although the high MAP and EC
      detection in CIR patients suggested that colonization is, at least, partially
      dependent on increased gut permeability. Nevertheless, facilitative mechanisms
      between a susceptible host and these two potential human pathogens may allow
      their implication in CD pathogenesis.

PMID- 25994084
TI  - Temperature dependence of DNA translocations through solid-state nanopores.
AB  - In order to gain a better physical understanding of DNA translocations through
      solid-state nanopores, we study the temperature dependence of lambda-DNA
      translocations through 10 nm diameter silicon nitride nanopores, both
      experimentally and theoretically. The measured ionic conductance G, the DNA
      induced ionic-conductance blockades [Formula: see text] and the event frequency
      Gamma all increase with increasing temperature while the DNA translocation time
      tau decreases. G and [Formula: see text] are accurately described when bulk and
      surface conductances of the nanopore are considered and access resistance is
      incorporated appropriately. Viscous drag on the untranslocated part of the DNA
      coil is found to dominate the temperature dependence of the translocation times
      and the event rate is well described by a balance between diffusion and
      electrophoretic motion. The good fit between modeled and measured properties of
      DNA translocations through solid-state nanopores in this first comprehensive
      temperature study, suggest that our model captures the relevant physics of the
      process. 

PMID- 25994085
TI  - Different polyamine pathways from bacteria have replaced eukaryotic spermidine
      biosynthesis in ciliates Tetrahymena thermophila and Paramecium tetaurelia.
AB  - The polyamine spermidine is absolutely required for growth and cell proliferation
      in eukaryotes, due to its role in post-translational modification of essential
      translation elongation factor eIF5A, mediated by deoxyhypusine synthase. We have
      found that free-living ciliates Tetrahymena and Paramecium lost the eukaryotic
      genes encoding spermidine biosynthesis: S-adenosylmethionine decarboxylase
      (AdoMetDC) and spermidine synthase (SpdSyn). In Tetrahymena, they were replaced
      by a gene encoding a fusion protein of bacterial AdoMetDC and SpdSyn, present as
      three copies. In Paramecium, a bacterial homospermidine synthase replaced the
      eukaryotic genes. Individual AdoMetDC-SpdSyn fusion protein paralogues from
      Tetrahymena exhibit undetectable AdoMetDC activity; however, when two paralogous
      fusion proteins are mixed, AdoMetDC activity is restored and spermidine is
      synthesized. Structural modelling indicates a functional active site is
      reconstituted by sharing critical residues from two defective protomers across
      the heteromer interface. Paramecium was found to accumulate homospermidine,
      suggesting it replaces spermidine for growth. To test this concept, a budding
      yeast spermidine auxotrophic strain was found to grow almost normally with
      homospermidine instead of spermidine. Biosynthesis of spermidine analogue
      aminopropylcadaverine, but not exogenously provided norspermidine, correlated
      with some growth. Finally, we found that diverse single-celled eukaryotic
      parasites and multicellular metazoan Schistosoma worms have lost the spermidine
      biosynthetic pathway but retain deoxyhypusine synthase. 

PMID- 25994086
TI  - Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian
      glucose metabolism.
AB  - Circulating carbohydrates are an essential energy source, perturbations in which
      are pathognomonic of various diseases, diabetes being the most prevalent. Yet
      many of the genes underlying diabetes and its characteristic hyperglycaemia
      remain elusive. Here we use physiological and genetic interrogations in D.
      melanogaster to uncover the 'glucome', the complete set of genes involved in
      glucose regulation in flies. Partial genomic screens of ~1,000 genes yield ~160
      hyperglycaemia 'flyabetes' candidates that we classify using fat body- and muscle
      specific knockdown and biochemical assays. The results highlight the minor
      glucose fraction as a physiological indicator of metabolism in Drosophila. The
      hits uncovered in our screen may have conserved functions in mammalian glucose
      homeostasis, as heterozygous and homozygous mutants of Ck1alpha in the murine
      adipose lineage, develop diabetes. Our findings demonstrate that glucose has a
      role in fly biology and that genetic screenings carried out in flies may increase
      our understanding of mammalian pathophysiology. 

PMID- 25994087
TI  - Biogenesis of protein bodies during legumin accumulation in developing olive
      (Olea europaea L.) seed.
AB  - Much of our current knowledge about seed development and differentiation
      regarding reserves synthesis and accumulation come from monocot (cereals) plants.
      Studies in dicotyledonous seeds differentiation are limited to a few species and
      in oleaginous species are even scarcer despite their agronomic and economic
      importance. We examined the changes accompanying the differentiation of olive
      endosperm and cotyledon with a focus on protein bodies (PBs) biogenesis during
      legumin protein synthesis and accumulation, with the aim of getting insights and
      a better understanding of the PBs' formation process. Cotyledon and endosperm
      undergo differentiation during seed development, where an asynchronous time
      course of protein synthesis, accumulation, and differential PB formation patterns
      was found in both tissues. At the end of seed maturation, a broad population of
      PBs, particularly in cotyledon cells, was distinguishable in terms of number per
      cell and morphometric and cytochemical features. Olive seed development is a
      tissue-dependent process characterized by differential rates of legumin
      accumulation and PB formation in the main tissues integrating seed. One of the
      main features of the impressive differentiation process is the specific formation
      of a broad group of PBs, particularly in cotyledon cells, which might depend on
      selective accumulation and packaging of proteins and specific polypeptides into
      PBs. The nature and availability of the major components detected in the PBs of
      olive seed are key parameters in order to consider the potential use of this
      material as a suitable source of carbon and nitrogen for animal or even human
      use.

PMID- 25994088
TI  - Oligonucleotide Probes for ND-FISH Analysis to Identify Rye and Wheat
      Chromosomes.
AB  - Genomic in situ hybridization (GISH) has been widely used to detect rye (Secale
      cereale L.) chromosomes in wheat (Triticum aestivum L.) introgression lines. The
      routine procedure of GISH using genomic DNA of rye as a probe is time-consuming
      and labor-intensive because of the preparation and labeling of genomic DNA of rye
      and denaturing of chromosomes and probes. In this study, new oligonucleotide
      probes Oligo-1162, Oligo-pSc200 and Oligo-pSc250 were developed. The three new
      probes can be used for non-denaturing fluorescence in situ hybridization (ND
      FISH) assays and replace genomic DNA of rye as a probe to discriminate rye
      chromosomes in wheat backgrounds. In addition, previously developed
      oligonucleotide probes Oligo-pSc119.2-1, Oligo-pSc119.2-2, Oligo-pTa535-1, Oligo
      pTa535-2, Oligo-pTa71-2, Oligo-pAWRC.1 and Oligo-CCS1 can also be used for ND
      FISH of wheat and rye. These probes have provided an easier, faster and more cost
      effective method for the FISH analysis of wheat and hybrids derived from wheat *
      rye. 

PMID- 25994089
TI  - In vitro study of the growth, development and pathogenicity responses of Fusarium
      oxysporum to phthalic acid, an autotoxin from Lanzhou lily.
AB  - Continuous monoculture of Lanzhou lily (Lilium davidii var. unicolor Cotton)
      results in frequent incidence of fusarium wilt caused by Fusarium oxysporum.
      Phthalic acid (PA), a principal autotoxin from root exudates of Lanzhou lily, is
      involved in soil sickness by inducing autotoxicity. The aim of this study was to
      evaluate the direct allelopathic effects of PA on the growth, development and
      pathogenicity of F. oxysporum in vitro based on an ecologically relevant soil
      concentration. The results showed that PA slightly but not significantly
      inhibited the colony growth (mycelial growth) and fungal biomass of F. oxysporum
      at low concentrations ranging from 0.05 to 0.5 mM, and significantly inhibited
      the colony growth at the highest concentration (1 mM). None of the PA
      concentrations tested significantly inhibited the conidial germination and
      sporulation of F. oxysporum in liquid medium. However, mycotoxin (fusaric acid)
      yield and pathogenesis-related hydrolytic enzyme (protease, pectinase, cellulase,
      and amylase) activities were significantly stimulated in liquid cultures of F.
      oxysporum containing PA at >= 0.25 mM. We conclude that PA at a soil level (i.e.
      0.25 mM) is involved in plant-pathogen allelopathy as a stimulator of mycotoxin
      production and hydrolytic enzyme activities in F. oxysporum, which is possibly
      one of the mechanisms responsible for promoting the wilt disease of lily.

PMID- 25994090
TI  - 'Red blood transfusion in patients undergoing cardiac surgery reply'.

PMID- 25994091
TI  - Dose reduction of biological treatment in patients with axial spondyloarthritis
      in clinical remission: Are there any differences between patients who relapsed
      and to those who remained in low disease activity?
AB  - The aim of the study was to assess whether dose reduction of biological treatment
      in patients with axial spondyloarthritis in sustained remission could be
      effective to maintain remission or low disease activity at 1 year and to explore
      baseline differences between patients who remained in remission or low disease
      activity and patients who relapsed. This was a prospective, observational study.
      All consecutive patients with axial spondyloarthritis in sustained remission were
      included and received low doses of anti-TNF-alpha according to a dose reduction
      protocol. At 1 year, the percentage of patients in remission or low disease
      activity and in relapse and the differences in baseline characteristics between
      the two groups were calculated. Of forty-two patients, 76.2 % remained in
      remission or low disease activity at 1 year. A significant shorter duration of
      remission before dose reduction, shorter duration of biological treatment and
      shorter disease duration were observed in the relapse group. Most of our patients
      with axial spondyloarthritis remained in remission or low disease activity at 1
      year after dosage reduction of biologics and shorter duration of remission,
      shorter duration of biological treatment and shorter disease duration
      discriminated the patients who relapsed.

PMID- 25994092
TI  - Evaluation of prolidase activity and oxidative status in patients with knee
      osteoarthritis: relationships with radiographic severity and clinical parameters.
AB  - We investigated serum prolidase activity and oxidative/antioxidative status in
      patients with knee osteoarthritis (OA) and evaluated its relationships with
      radiographic severity and clinical parameters. The study population consisted of
      137 patients with knee OA and 134 healthy volunteers. The severity of knee OA was
      classified according to the Kellgren-Lawrence criteria. Each patient was also
      evaluated clinically according to the Western Ontario and McMaster University
      Osteoarthritis Index (WOMAC). Serum prolidase activity was measured
      spectrophotometrically. Oxidative status was assessed by measuring serum lipid
      hydroperoxide (LOOH) and total oxidative status (TOS). Antioxidative status was
      assessed by measuring serum-free sulfhydryl groups (-SH = total thiol) and total
      antioxidant capacity (TAC). Oxidative stress index (OSI) was calculated. Serum
      prolidase activity was significantly lower in the knee OA group than in the
      control group (p < 0.001). The serum prolidase activities decreased with the
      severity of knee OA. Furthermore, serum LOOH, TOS, and OSI levels of the knee OA
      group were significantly higher than those of the controls (p < 0.001 for all),
      whereas TAC and -SH levels did not differ between the two groups (p > 0.05). In a
      multiple regression analysis, WOMAC score was independently associated with serum
      prolidase activity (beta = -0.340, p < 0.001). Decreased serum prolidase activity
      and elevated LOOH, TOS, and OSI levels may be associated with knee OA, and serum
      prolidase activity may be a useful adjunctive indicator of the progression of
      knee OA in follow-up. 

PMID- 25994093
TI  - Comparative efficacy and safety of tofacitinib, with or without methotrexate, in
      patients with active rheumatoid arthritis: a Bayesian network meta-analysis of
      randomized controlled trials.
AB  - This study aimed to assess the relative efficacy and safety of tofacitinib 5 and
      10 mg twice daily, or in combination with methotrexate (MTX), in patients with
      active RA. Randomized controlled trials (RCTs) examining the efficacy and safety
      of tofacitinib in patients with active RA were included in this network meta
      analysis. We performed a Bayesian network meta-analysis to combine the direct and
      indirect evidence from the RCTs. Ten RCTs including 4867 patients met the
      inclusion criteria. There were 21 pairwise comparisons including 11 direct
      comparisons of seven interventions. The ACR20 response rate was significantly
      higher in the tofacitinib 10 mg + MTX group than in the placebo and MTX groups
      (OR 7.56, 95 % credible interval (CrI) 3.07-21.16; OR 3.67, 95 % CrI 2.60-5.71,
      respectively). Ranking probabilities based on the surface under the cumulative
      ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest
      probability of being the best treatment for achieving the ACR20 response rate
      (SUCRA = 0.9254), followed by tofacitinib 5 mg + MTX (SUCRA = 0.7156), adalimumab
      40 mg + MTX (SUCRA = 0.6097), tofacitinib 10 mg (SUCRA = 0.5984), tofacitinib 5
      mg (SUCRA = 0.4749), MTX (SUCRA = 0.1674), and placebo (SUCRA = 0.0086). In
      contrast, the safety based on the number of withdrawals due to adverse events did
      not differ significantly among the seven interventions. Tofacitinib, at dosages 5
      and 10 mg twice daily, in combination with MTX, was the most efficacious
      intervention for active RA and was not associated with a significant risk for
      withdrawals due to adverse events. 

PMID- 25994094
TI  - Behaviour change interventions to promote physical activity in rheumatoid
      arthritis: a systematic review.
AB  - Research has shown that people who have rheumatoid arthritis (RA) do not usually
      participate in enough physical activity to obtain the benefits of optimal
      physical activity levels, including quality of life, aerobic fitness and disease
      related characteristics. Behaviour change theory underpins the promotion of
      physical activity. The aim of this systematic review was to explore behaviour
      change interventions which targeted physical activity behaviour in people who
      have RA, focusing on the theory underpinning the interventions and the behaviour
      change techniques utilised using specific behaviour change taxonomy. An
      electronic database search was conducted via EBSCOhost, PubMed, Cochrane Central
      Register of Controlled Trials and Web of Science databases in August 2014, using
      Medical Subject Headings and keywords. A manual search of reference lists was
      also conducted. Randomised control trials which used behaviour change techniques
      and targeted physical activity behaviour in adults who have RA were included. Two
      reviewers independently screened studies for inclusion. Methodological quality
      was assessed using the Cochrane risk of bias tool. Five studies with 784
      participants were included in the review. Methodological quality of the studies
      was mixed. The studies consisted of behaviour change interventions or combined
      practical physical activity and behaviour change interventions and utilised a
      large variety of behaviour change techniques. Four studies reported increased
      physical activity behaviour. All studies used subjective methods of assessing
      physical activity with only one study utilising an objective measure. There has
      been varied success of behaviour change interventions in promoting physical
      activity behaviour in people who have RA. Further studies are required to develop
      and implement the optimal behaviour change intervention in this population. 

PMID- 25994096
TI  - Nutrient intake of pregnant women at high risk of gestational diabetes.
AB  - BACKGROUND: The prevalence of gestational diabetes (GDM) has been increasing
      along with the obesity pandemic. It is associated with pregnancy complications
      and a risk of type 2 diabetes. OBJECTIVE: To study nutrient intake among pregnant
      Finnish women at increased risk of GDM due to obesity or a history of GDM.
      DESIGN: Food records from obese women or women with GDM history (n=394) were
      examined at baseline (<=20 weeks of pregnancy) of the Finnish Gestational
      Diabetes Prevention Study. RESULTS: The pregnant women had a mean fat intake of
      33 en% (SD 7), saturated fatty acids (SFA) 12 en% (SD 3), and carbohydrate 46 en%
      (SD 6). Sucrose intake among pregnant women with GDM history was 7 en% (SD 3),
      which was different from the intake of the other pregnant women, 10 en% (SD 4)
      (p<0.001). Median intakes of folate and vitamins A and D provided by food sources
      were below the Finnish national nutrition recommendation, but, excluding vitamin
      A, supplements raised the total intake to the recommended level. The frequency of
      use of dietary supplements among pregnant women was 77%. CONCLUSIONS: The
      observed excessive intake of SFA and low intake of carbohydrates among women at
      high risk of GDM may further increase their risk of GDM. A GDM history, however,
      seems to reduce sucrose intake in a future pregnancy. Pregnant women at high risk
      of GDM seem to have insufficient intakes of vitamin D and folate from food and
      thus need supplementation, which most of them already take.

PMID- 25994095
TI  - Theory of planned behavior and adherence in chronic illness: a meta-analysis.
AB  - Social-cognitive models such as the theory of planned behavior have demonstrated
      efficacy in predicting behavior, but few studies have examined the theory as a
      predictor of treatment adherence in chronic illness. We tested the efficacy of
      the theory for predicting adherence to treatment in chronic illness across
      multiple studies. A database search identified 27 studies, meeting inclusion
      criteria. Averaged intercorrelations among theory variables were computed
      corrected for sampling error using random-effects meta-analysis. Path-analysis
      using the meta-analytically derived correlations was used to test theory
      hypotheses and effects of moderators. The theory explained 33 and 9 % of the
      variance in intention and adherence behavior respectively. Theoretically
      consistent patterns of effects among the attitude, subjective norm, perceived
      behavioral control, intention and behavior constructs were found with small-to
      medium effect sizes. Effect sizes were invariant across behavior and measurement
      type. Although results support theory predictions, effect sizes were small,
      particularly for the intention-behavior relationship.

PMID- 25994097
TI  - Ancient pathogens in museal dry bone specimens: analysis of paleocytology and
      aDNA.
AB  - Bone samples investigated in this study derive from the pathologic-anatomical
      collection of the Natural History Museum of Vienna. In order to explore the
      survival of treponemes and treponemal ancient DNA in museal dry bone specimens,
      we analyzed three individuals known to have been infected with Treponema pallidum
      pallidum. No reproducible evidence of surviving pathogen's ancient DNA (aDNA) was
      obtained, despite the highly sensitive extraction and amplification techniques
      (TPP15 and arp). Additionally, decalcification fluid of bone sections was smear
      stained with May-Gruenwald-Giemsa. The slides were examined using direct light
      microscope and dark field illumination. Remnants of spirochetal structures were
      detectable in every smear. Our results demonstrate that aDNA is unlikely to
      survive, but spirochetal remains are stainable and thus detectable. 

PMID- 25994098
TI  - Effect of summer conditions and shade on behavioural indicators of thermal
      discomfort in Holstein dairy and Belgian Blue beef cattle on pasture.
AB  - Using behavioural indicators of thermal discomfort, that is, shade seeking,
      panting scores (PS) and respiration rate (RR), we evaluated the effect of hot
      summer conditions and shade, for a herd of adult Holstein dairy cows and a herd
      of Belgian Blue beef cows kept on pasture in a temperate area (Belgium). During
      the summer of 2012, both herds were kept on pasture without access to shade (NS).
      During the summers of 2011 and 2013 each herd was divided into one group with (S)
      and one without (NS) access to shade. Shade was provided by young trees with
      shade cloth (80% reduction in solar radiation) hung between them. For S cows, we
      investigated how shade use was related to hot conditions as quantified by six
      climatic indices. The heat load index (HLI), which incorporates air temperature
      and humidity, solar radiation and wind speed, was the best predictor of the six
      indices tested. In 2011, there was a relatively high threshold for use of shade.
      When HLI=90, shade use probability reached 17% for dairy cows and 27% for beef
      cows. In 2013, however, at HLI=90, shade use probability reached 48% for dairy
      cows and 41% for beef cows. For animals from the NS treatment we determined the
      effect of hot summer conditions on RR and PS (with 0=no panting and 4.5=extreme
      panting). In both types of cattle, an increase in black globe temperature was the
      best predictor for increasing RR and PS. Furthermore, we determined how the
      effect of hot summer conditions on RR and PS was affected by the use of shade.
      Under hot conditions (black globe temperature ? 30 degrees C), >50% of the
      animals under shade retained normal PS and RR (PS<1 and RR<90 breaths per
      minute), whereas normal RR and PS were significantly less prevalent for animals
      outside shade. Our findings suggest that, even in temperate summers, heat can
      induce thermal discomfort in cattle, as evidenced by increases in shade use, RR
      and PS, and that shade increases thermal comfort.

PMID- 25994099
TI  - An infrared spectroscopic and theoretical study on (CH3)3N-H(+)-(H2O)(n), n = 1
      22: highly polarized hydrogen bond networks of hydrated clusters.
AB  - Infrared spectra of protonated trimethylamine (TMA)-water clusters, (CH3)3N-H(+)
      (H2O)n (n = 1-22) were measured in the OH stretching vibrational region by size
      selective photodissociation spectroscopy. Density functional theory calculations
      of stable structures were performed, and temperature dependence of the isomer
      populations and infrared spectra was also simulated by the harmonic superposition
      approximation approach to analyze hydrogen bond network structures in the
      clusters. It was shown that the excess proton (H(+)) in this system localizes on
      the TMA moiety regardless of cluster size. In the small-sized clusters, many
      isomers coexist and their hydrogen bond networks are highly polarized to induce
      the large charge-dipole interaction to stabilize the excess proton. Magic number
      behavior is not observed at around the magic number size (n = 21) of protonated
      water clusters and its implication on the hydrogen bond network structures is
      discussed. 

PMID- 25994100
TI  - PER2 Differentially Regulates Clock Phosphorylation versus Transcription by
      Reciprocal Switching of CK1epsilon Activity.
AB  - Casein kinase 1epsilon (CK1epsilon) performs key phosphorylation reactions in the
      circadian clock mechanism that determine period. We show that the central clock
      protein PERIOD2 (PER2) not only acts as a transcriptional repressor but also
      inhibits the autoinactivation of CK1epsilon, thereby promoting CK1epsilon
      activity. Moreover, PER2 reciprocally regulates CK1epsilon's ability to
      phosphorylate other substrates. On output pathway substrates (e.g., P53), PER2
      inhibits the activity of CK1epsilon. However, in the case of central clock
      proteins (e.g., CRYPTOCHROME2), PER2 stimulates the CK1epsilon-mediated
      phosphorylation of CRY2. CK1epsilon activity is temperature compensated on the
      core clock substrate CRY2 but not on output substrates, for example, the
      physiological output protein substrate P53 and its nonphysiological correlate,
      bovine serum albumin (BSA). These results indicate heretofore unrecognized
      pivotal roles of PER2; it not only regulates the central
      transcription/translation feedback loop but also differentially controls kinase
      activity CK1epsilon in its phosphorylation of central clock (e.g., CRY2) versus
      output (e.g., P53) substrates. 

PMID- 25994101
TI  - period and timeless mRNA Splicing Profiles under Natural Conditions in Drosophila
      melanogaster.
AB  - Previous analysis of Drosophila circadian behavior under natural conditions has
      revealed a number of novel and unexpected features. Here we focus on the
      oscillations of per and tim mRNAs and their posttranscriptional regulation and
      observe significant differences in molecular cycling under laboratory and natural
      conditions. In particular, robust per mRNA cycling from fly heads is limited to
      the summers, whereas tim RNA cycling is observed throughout the year. When both
      transcripts do cycle, their phases are similar, except for the very warmest
      summer months. We also study the natural splicing profiles of per and tim
      transcripts and observe a clear relationship between temperature and splicing. In
      natural conditions, we confirm the relationship between accumulation of the
      per(spliced) variant, low temperature, and the onset of the evening component of
      locomotor activity, first described in laboratory conditions. Intriguingly, in
      the case of tim splicing, we detect the opposite relationship, with tim(spliced)
      expression increasing at higher temperatures. A first characterization of the 4
      different TIM protein isoforms (resulting from the combination of the natural N
      terminus length polymorphism and the C-terminus alternative splicing) using the 2
      hybrid assay showed that the TIM(unspliced) isoforms have a stronger affinity for
      CRY, but not for PER, suggesting that the tim 3' splicing could have
      physiological significance, possibly in temperature entrainment and/or adaptation
      to seasonal environments. 

PMID- 25994102
TI  - Day-night variability of hematoma expansion in patients with spontaneous
      intracerebral hemorrhage.
AB  - The levels of several coagulation factors, able to influence hemostatic balance,
      display circadian variations. We hypothesized that the onset and extent of
      hematoma expansion (HE) following intracerebral hemorrhage (ICH) also display
      diurnal patterns. We reviewed clinical, laboratory, and radiological data from
      111 consecutive patients with spontaneous ICH who had baseline head computed
      tomography (CT) scans within 3 h of ICH onset and follow-up CT during the
      following 72 h. We defined any HE (AHE) as any increase in hematoma volume from
      baseline to follow-up CT and significant HE (SHE) as an absolute increase in
      hematoma volume >6 mL or relative increase >33%. We categorized the patients into
      2 groups based on the timing of the initial CT scans--day group (from 0800 to
      2000 h) and night group (from 2000 to 0800 h)--and performed logistic regression
      analyses. We also analyzed the differences in the rates of HE between the groups
      during six 4-h periods spanning 24 h, using chi(2) tests. We found that the rates
      of AHE and SHE were higher in the day versus night group (75% vs. 48%; p = 0.009
      for AHE and 47.6% vs. 25.9%; p = 0.047 for SHE). On multivariable logistic
      regression, day group assignment was independently associated with AHE (adjusted
      odds ratio = 3.53; p = 0.008) but not with SHE. Both AHE and SHE peaked in the
      early afternoon (1200-1600 h) and reached a nadir during the 2000 to 2400 h time
      period, and they were significantly different between the time periods (0000
      0400, 0400-0800, 0800-1200, 1200-1600, 1600-2000, and 2000-2400 h); p = 0.002 and
      0.029, respectively. These exploratory findings support the presence of a daily
      pattern in the occurrence of HE, with a higher risk during the day hours. Our
      results could have implications for future therapeutic efforts targeting HE in
      ICH and for the triage of ICH patients. They require further validation.

PMID- 25994104
TI  - Sequential separation of ultra-trace U, Th, Pb, and lanthanides using a simple
      automatic system.
AB  - Uranium, thorium, lead, and the lanthanides were automatically and sequentially
      separated with a single anion-exchange column. This separation was achieved using
      eluents consisting of a simple and highly pure acid mixture of HCl, HNO3, acetic
      acid, and HF. The elements of interest were separated from the major
      constituents, which included alkaline metal elements, alkaline earth metal
      elements, and iron. This simple and automatic system is driven with pressurized
      nitrogen gas and controlled using a computer program. An optimized separation was
      accomplished under the following conditions: a 50 mm long and 2 mm diameter
      column, 11 MUm diameter anion-exchange resin, and a 35 MUL min(-1) flow rate.
      Using this system, 50 ng of varied elements in a 100 MUL feed solution were
      perfectly separated within 5 h with >400 decontamination factors and >95% yield.
      In order to evaluate the performance of this system, a reference powdered rock
      sample was separated using this system. Abundances of objective elements,
      including 0.23 ng of lutetium, were accurately determined without corrections of
      chemical recovery yield or subtraction of the process blank. This separation
      technique saves time and effort for chemical processing, and is useful for ultra
      trace quantitative and isotopic analyses of elements in small environmental
      samples. 

PMID- 25994103
TI  - Selective Distribution of Retinal Input to Mouse SCN Revealed in Analysis of
      Sagittal Sections.
AB  - The suprachiasmatic nucleus (SCN) is the locus of the master circadian clock,
      setting the daily rhythms in physiology and behavior and synchronizing these
      responses to the local environment. The most important of these phase-setting
      cues derive from the light-dark cycle and reach the SCN directly via the
      retinohypothalamic tract (RHT). The SCN contains anatomically and functionally
      heterogeneous populations of cells. Understanding how these neurons access
      information about the photic environment so as to set the phase of daily
      oscillation requires knowledge of SCN innervation by the RHT. While retinal
      innervation of the SCN has long been a topic of interest, the information is
      incomplete. In some instances, studies have focused on the caudal aspect of the
      nucleus, which contains the core region. In other instances, subregions of the
      nucleus have been delineated based on projections of where specific peptidergic
      cell types lie, rather than based on double or triple immunochemical staining of
      distinct populations of cells. Here, we examine the full extent of the mouse SCN
      using cholera toxin beta (CTbeta) as a tracer to analyze RHT innervation in
      triple-labeled sagittal sections. Using specific peptidergic markers to identify
      clusters of SCN cells, we find 3 distinct patterns. First is an area of dense RHT
      innervation to the core region, delineated by gastrin-releasing peptide (GRP) and
      vasoactive intestinal peptide (VIP) immunoreactive cells. Second is an area of
      moderate RHT fiber clusters, bearing arginine-vasopressin (AVP)-positive cells
      that lie close to the core. Finally, the outermost, shell, and rostral AVP
      containing regions of the SCN have few to no detectable retinal fibers. These
      results point to a diversity of inputs to individual SCN cell populations and
      suggest variation in the responses that underlie photic phase resetting. 

PMID- 25994105
TI  - The impact of rare EGFR mutations on the treatment response of patients with non
      small cell lung cancer.
AB  - Mutational activation of the epidermal growth factor receptor (EGFR) gene is
      implicated in lung cancer; clinical and cancer genome sequencing studies have
      identified hundreds of mutations in the protein kinase domain. EGFR mutation
      testing usually focuses on common mutations like the exon 19 deletion and exon 21
      point mutation (L858R). However, molecular screening methods have started to
      extend beyond identification of classic EGFR mutations to prevent exclusion of
      patients with rare or complex mutations who may benefit from anti-EGFR therapy.
      Rare EGFR-mutated non-small-cell lung cancers are heterogeneous: exon 20
      insertions lack sensitivity to tyrosine kinase inhibitors while exon 18 or
      complex mutations are more sensitive and require individual assessment. Until
      testing for uncommon EGFR mutations evolves and studies with large number of
      patients are performed, knowledge of this field will remain limited.

PMID- 25994106
TI  - Reversible conversion of valence-tautomeric copper metal-organic frameworks
      dependent single-crystal-to-single-crystal oxidation/reduction: a redox
      switchable catalyst for C-H bonds activation reaction.
AB  - Upon single-crystal-to-single-crystal (SCSC) oxidation/reduction, reversible
      structural transformations take place between the anionic porous zeolite-like
      Cu(I) framework and a topologically equivalent neutral Cu(I)Cu(II) mixed-valent
      framework. The unique conversion behavior of the Cu(I) framework endowed it as a
      redox-switchable catalyst for the direct arylation of heterocycle C-H bonds. 

PMID- 25994107
TI  - A method for estimating the glomerular filtration rate in conscious monkeys.
AB  - To establish a method for estimating the glomerular filtration rate (GFR) in
      conscious monkeys, the radiographic contrast medium iodixanol and the standard
      agent inulin were coadministered as tracers to male cynomolgus monkeys (Macaca
      fascicularis) as a bolus injection; blood was collected after 60, 90 and 120 min.
      An equation based on a single-blood-sample method derived from Jacobsson's
      formula was prepared using the data from healthy and saline- and gentamicin
      treated monkeys by a multisample strategy with iodixanol. The GFR using the
      equation with iodixanol was in agreement with that from the multisample method
      with inulin or iodixanol. When the GFR decreased to more than 60% of the basal
      reference level, serum creatinine concentrations tended to increase, whereas
      serum blood urea nitrogen concentrations fluctuated. The results suggest that the
      single-sample-blood method with iodixanol is a practical tool for estimating the
      monkey GFR in a toxicological research setting therefore minimizing animal
      sufferings.

PMID- 25994108
TI  - Medical interventions to reverse pulmonary hypoplasia in the animal model of
      congenital diaphragmatic hernia: A systematic review.
AB  - OBJECTIVE: We aimed to systematically review all published pre-clinical research
      on prenatal medical treatment of pulmonary hypoplasia in congenital diaphragmatic
      hernia (CDH). Background The neonatal mortality due to isolated CDH remains high.
      Whether fetal endoscopic tracheal occlusion (FETO) reduces mortality is still to
      be demonstrated. Therefore more potent preferentially medical therapy would be
      welcomed. Methods We searched MEDLINE (Pubmed), Embase and the Web of Science
      including all studies from the earliest date (1951) to December 2013. Article
      quality was assessed using the modified CAMRADES checklist. Inclusion criteria
      were those animal studies addressing prenatal medical interventions and principal
      variables were confirmation of a diaphragmatic defect, lung to body weight ratio
      (LBWR), formal airway morphometry or DNA/protein content. Results In total 983
      articles were identified. Following abstract review, 96 articles were assessed by
      two authors in agreement with a third for eligibility. Of these, 43 were included
      in the final analysis. The median number of study quality checklist items
      (maximum 10) scored was 4 (IQ range: 2-5). Thirty (69.8%) of studies were in the
      nitrofen rat. The majority were treated with vitamins or glucocorticoids. Single
      studies reported some improvement in lung morphology with alternative therapies.
      It was impossible to identify a pattern in animal model selection or creation,
      mode, time point or duration of treatment and readouts. Only one study reported a
      sample size calculation. Conclusion Comparison in pre-clinical studies in CDH is
      challenging due to methodological variation. Agreed standardized methods need to
      be applied in future investigation of new medical therapies.

PMID- 25994110
TI  - Melatonin protects inner ear against radiation damage in rats.
AB  - OBJECTIVES/HYPOTHESIS: To examine the effects of N-acetyl-5-methoxytryptamine
      (melatonin) on radiation-induced inner ear damage. STUDY DESIGN: An experimental
      animal model. METHODS: Forty rats were randomized into five groups, as follows:
      1) melatonin and then radiotherapy group (n = 8), which received intraperitoneal
      (i.p.) melatonin (5 mg/kg) followed by irradiation 30 minutes later; 2)
      radiotherapy and then melatonin group (n = 8), which received irradiation with
      i.p. melatonin (5 mg/kg) 30 minutes later; 3) melatonin group (n = 8), which
      received i.p. melatonin (5 mg/kg); 4) radiotherapy group (n = 8), which underwent
      only irradiation; 5) and the control group (n = 8), which received i.p. 0.9%
      NaCl. The medications and irradiation were administered for 5 days. All rats
      underwent the distortion product otoacoustic emission (DPOAE) test before and 10
      days after the experiment. The middle ears of the rats were excised, and
      assessment of tissue alterations in the organs of Corti, spiral ganglions, and
      stria vascularis were compared among the groups. RESULTS: In the radiotherapy
      group, the DPOAE amplitudes at frequencies of 4000 to 6000 Hz were significantly
      decreased when compared with the controls. The DPOAE amplitudes both in the
      melatonin and then radiotherapy group and the radiotherapy and then melatonin
      group exhibited better values than they did in the radiotherapy group.
      Histopathological evidence of damage to the organs of Corti, spiral ganglions,
      and stria vascularis damage was markedly reduced in both these two groups when
      compared to the radiotherapy group. CONCLUSION: These results indicate that
      melatonin may have significant ameliorative effects on cochlear damage secondary
      to ionizing radiation.

PMID- 25994109
TI  - Prediction of remission in obsessive compulsive disorder using a novel machine
      learning strategy.
AB  - The study objective was to apply machine learning methodologies to identify
      predictors of remission in a longitudinal sample of 296 adults with a primary
      diagnosis of obsessive compulsive disorder (OCD). Random Forests is an ensemble
      machine learning algorithm that has been successfully applied to large-scale data
      analysis across vast biomedical disciplines, though rarely in psychiatric
      research or for application to longitudinal data. When provided with 795 raw and
      composite scores primarily from baseline measures, Random Forest regression
      prediction explained 50.8% (5000-run average, 95% bootstrap confidence interval
      [CI]: 50.3-51.3%) of the variance in proportion of time spent remitted. Machine
      performance improved when only the most predictive 24 items were used in a
      reduced analysis. Consistently high-ranked predictors of longitudinal remission
      included Yale-Brown Obsessive Compulsive Scale (Y-BOCS) items, NEO items and
      subscale scores, Y-BOCS symptom checklist cleaning/washing compulsion score, and
      several self-report items from social adjustment scales. Random Forest
      classification was able to distinguish participants according to binary remission
      outcomes with an error rate of 24.6% (95% bootstrap CI: 22.9-26.2%). Our results
      suggest that clinically-useful prediction of remission may not require an
      extensive battery of measures. Rather, a small set of assessment items may
      efficiently distinguish high- and lower-risk patients and inform clinical
      decision-making.

PMID- 25994111
TI  - Glycocalyx-Mimicking Nanoparticles for Stimulation and Polarization of
      Macrophages via Specific Interactions.
AB  - Malignant tumors develop multiple mechanisms to impair and escape from antitumor
      immune responses, of which tumor-associated macrophages that often show
      immunosuppressive phenotype (M2), play a critical role in tumor-induced
      immunosuppression. Therefore, strategies that can reverse M2 phenotype and even
      enhance immune-stimulation function of macrophage would benefit tumor
      immunotherapy. In this paper, self-assembled glyco-nanoparticles (glyco-NPs), as
      artificial glycocalyx, have been found to be able to successfully induce the
      polarization of mouse primary peritoneal macrophages from M2 to inflammatory type
      (M1). The polarization change was evidenced by the decreased expression of cell
      surface signaling molecules CD206 and CD23, and the increased expression of CD86.
      Meanwhile, secretion of cytokines supported this polarization change as well.
      More importantly, this phenomenon is observed not only in vitro, but also in
      vivo. As far as we known, this is the first report about macrophage polarization
      being induced by synthetic nanomaterials. Moreover, preparation, characterization
      of these glyco-NPs and their interaction with the macrophages are also
      demonstrated. 

PMID- 25994112
TI  - Probing Cu(I) in homogeneous catalysis using high-energy-resolution fluorescence
      detected X-ray absorption spectroscopy.
AB  - Metal-to-ligand charge transfer excitations in Cu(I) X-ray absorption spectra are
      introduced as spectroscopic handles for the characterization of species in
      homogeneous catalytic reaction mixtures. Analysis is supported by correlation of
      a spectral library to calculations and to complementary spectroscopic parameters.

PMID- 25994113
TI  - Matrix-assisted laser desorption/ionisation (MALDI) TOF analysis identifies serum
      angiotensin II concentrations as a strong predictor of all-cause and breast
      cancer (BCa)-specific mortality following breast surgery.
AB  - MALDI-TOF MS was used to recognise serum peptidome profiles predictive of
      mortality in women affected by early BCa. Mortality was analysed based on signal
      profiling, and appropriate statistics were used. The results indicate that four
      signals were increased in deceased patients compared with living patients. Three
      of the four signals were individually associated with all-cause mortality, but
      only one having mass/charge ratio (m/z) 1,046.49 was associated with BCa-specific
      mortality and was the only peak to maintain an independent prognostic role after
      multivariate analysis. Two groups exhibiting different mortality probabilities
      were identified after clustering patients based on the expression of the four
      peptides, but m/z 1,046.49 was exclusively expressed in the cluster exhibiting
      the worst mortality outcome, thus confirming the crucial value of this peptide.
      The specific role of this peak was confirmed by competing risk analysis. MS
      findings were validated by ELISA analysis after demonstrating that m/z 1,046.49
      structurally corresponded to Angiotensin II (ATII). In fact, mortality results
      obtained after arbitrarily dividing patients according to an ATII serum value of
      255 pg/ml (which corresponds to the 66(th) percentile value) were approximately
      comparable to those previously demonstrated when the same patients were analysed
      according to the expression of signal m/z 1,046.49. Similarly, ATII levels were
      specifically correlated with BCa-related deaths after competing risk analysis. In
      conclusion, ATII levels were increased in women who exhibited worse mortality
      outcomes, reinforcing the evidence that this peptide potentially significantly
      affects the natural history of early BCa. Our findings also confirm that MALDI
      TOF MS is an efficient screening tool to identify novel tumour markers and that
      MS findings can be rapidly validated through less complex techniques, such as
      ELISA. 

PMID- 25994114
TI  - Evaluating endoglucanase Cel7B-lignin interaction mechanisms and kinetics using
      quartz crystal microgravimetry.
AB  - The kinetics and mechanisms of protein interactions with solid surfaces are
      important to fields as diverse as industrial biocatalysis, biomedical
      engineering, food science, and cell biology. The nonproductive adsorption of
      cellulase enzymes to lignin, a plant cell wall polymer, reduces their
      effectiveness in saccharifying biomass. Cellulase has been shown to interact with
      lignin, but the heterogeneity of lignin surfaces, challenges in measuring
      irreversible components of these interactions, and fast adsorption rates make
      quantifying the reaction kinetics difficult. This work employs quartz crystal
      microgravimetry with dissipation monitoring (QCM-D) for real-time measurement of
      adsorbed mass on a flat lignin surface. We have developed a method for casting
      homogeneous lignin films that are chemically similar to lignin found in
      pretreated biomass, and used QCM-D to compare three models of reversible
      irreversible binding behavior: a single-site transition model, a transition model
      with changing adsorbate footprint, and a two-site transition model. Of the three
      models tested, the two-site transition model provides the only kinetic mechanism
      able to describe the behavior of Cel7B binding to lignin. While the direct
      implications of lignin-cellulase interactions may be limited to biomass
      deconstruction for renewable energy and green chemistry, the analytical and
      experimental methods demonstrated in this work are relevant to any system in
      which the kinetics and reaction mechanism of reversible and irreversible protein
      adsorption at a solid-liquid interface are important.

PMID- 25994115
TI  - Responsive Polymer-Based Assemblies for Sensing Applications.
AB  - Poly (N-isopropylacrylamide) (pNIPAm)-based hydrogels and hydrogel particles
      (microgels) have been extensively studied since their discovery and
      "popularization" a few decades ago. While their uses seem to have no bounds, this
      Feature Article is focused on their development and application for sensing small
      molecules, macromolecules, and biomolecules. Hydrogel/microgel-based photonic
      materials with order in one, two, or three dimensions are highlighted, which
      exhibit optical properties that depend on the presence and concentration of
      various analytes. 

PMID- 25994117
TI  - Letter response to original article by Broughton et al "Seven Years of
      Cranioplasty in a Regional Neurosurgical Centre".

PMID- 25994116
TI  - The relationship between parental depressive symptoms and offspring
      psychopathology: evidence from a children-of-twins study and an adoption study.
AB  - BACKGROUND: Parental depressive symptoms are associated with emotional and
      behavioural problems in offspring. However, genetically informative studies are
      needed to distinguish potential causal effects from genetic confounds, and
      longitudinal studies are required to distinguish parent-to-child effects from
      child-to-parent effects. METHOD: We conducted cross-sectional analyses on a
      sample of Swedish twins and their adolescent offspring (n = 876 twin families),
      and longitudinal analyses on a US sample of children adopted at birth, their
      adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive
      symptoms were measured in parents, and externalizing and internalizing problems
      measured in offspring. Structural equation models were fitted to the data.
      RESULTS: Results of model fitting suggest that associations between parental
      depressive symptoms and offspring internalizing and externalizing problems remain
      after accounting for genes shared between parent and child. Genetic transmission
      was not evident in the twin study but was evident in the adoption study. In the
      longitudinal adoption study child-to-parent effects were evident. CONCLUSIONS: We
      interpret the results as demonstrating that associations between parental
      depressive symptoms and offspring emotional and behavioural problems are not
      solely attributable to shared genes, and that bidirectional effects may be
      present in intergenerational associations.

PMID- 25994118
TI  - Aspirin-mediated acetylation induces structural alteration and aggregation of
      bovine pancreatic insulin.
AB  - The simple aggregation of insulin under various chemical and physical stresses is
      still an important challenge for both pharmaceutical production and clinical
      formulation. In the storage form, this protein is subjected to various chemical
      modifications which alter its physicochemical and aggregation properties. Aspirin
      (acetylsalicylic acid) which is the most widely used medicine worldwide has been
      indicated to acetylate a large number of proteins both in vitro and in vivo. In
      this study, as insulin treated with aspirin at 37 degrees C, a significant level
      of acetylation was observed by flourescamine and o-phthalaldehyde assay. Also,
      different spectroscopic techniques, gel electrophoresis, and microscopic
      assessment were applied to compare the structural variation and
      aggregation/fibrillation propensity among acetylated and non-acetylated insulin
      samples. The results of spectroscopic assessments elucidate that acetylation
      induces insulin unfolding which is accompanied with the exposure of protein
      hydrophobic patches, a transition from alpha-helix to beta-sheet and increased
      propensity of the protein for aggregation. The kinetic studies propose that
      acetylation increases aggregation rate of insulin under both thermal and chemical
      stresses. Also, gel electrophoresis and dynamic light scattering experiments
      suggest that acetylation induces insulin oligomerization. Additionally, the
      results of Thioflavin T fluorescence study, Congo red absorption assessment, and
      microscopic analysis suggest that acetylation with aspirin enhances the process
      of insulin fibrillation. Overall, the increased susceptibility of acetylated
      insulin for aggregation may reflect the fact that this type of modification has
      significant structural destabilizing effect which finally makes the protein more
      vulnerable for pathogenic aggregation/fibrillation. 

PMID- 25994120
TI  - The impact of selectins on mortality in stable carotid atherosclerosis.
AB  - Cellular adhesion molecules also known as selectins promote recruitment of
      inflammatory cells into the arterial wall where they interact with lipid
      particles leading subsequently to plaque formation. The intercellular adhesion
      molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and the
      endothelial-leukocyte adhesion molecule 1 (ELAM-1) also known as E-selectin
      mediate the attachment of leukocytes and have been implicated in the
      destabilisation of atherosclerotic plaques. Therefore, we hypothesised that
      plasma selectin levels are associated with adverse clinical outcome. We
      prospectively studied 855 patients with sonographically confirmed carotid
      atherosclerosis. During a median follow-up of 6.2 years, corresponding to 5,551
      overall person-years, 275 patients (26 %) died. We detected a significant
      association between cardiovascular mortality and ICAM-1 (adjusted hazard ratio
      [HR]: 3.43, 95 % confidence interval [CI] 2.00-5.88, p< 0.001) as well as VCAM-1
      (adjusted HR: 2.51, 95 %CI 1.45-4.34, p=0.001) when comparing the fourth with the
      first quartile. Comparable results were obtained for all-cause mortality. In
      contrast, we could not detect a significant association between E-selectin and
      all-cause or cardiovascular mortality. We identified the selectins ICAM-1 and
      VCAM-1 as strong and independent predictors of all-cause and cardiovascular
      mortality in patients with stable carotid atherosclerosis. These molecules are
      elevated in states of endothelial activation and might assist to monitor anti
      atherosclerotic therapy and select those patients with carotid atherosclerosis,
      who are at higher risk for cardiovascular events. 

PMID- 25994121
TI  - Passive sampling for volatile organic compounds in indoor air-controlled
      laboratory comparison of four sampler types.
AB  - Correction for 'Passive sampling for volatile organic compounds in indoor air
      controlled laboratory comparison of four sampler types' by Todd McAlary et al.,
      Environ. Sci.: Processes Impacts, 2015, 17, 896-905.

PMID- 25994122
TI  - Antithymocyte globulin dosing effects on biopsy-proven acute rejection and
      infection risk.
AB  - BACKGROUND: Antithymocyte globulin (rATG) is a polyclonal antibody commonly used
      as induction therapy in kidney transplantation to reduce risk of allograft
      rejection. Currently there is no consensus on the optimal dosing. rATG is not FDA
      approved for induction therapy, so no dosing recommendations are provided by the
      manufacturer. Current kidney transplant guidelines do not provide dosing
      recommendations. The objective of this study was to evaluate effects of different
      cumulative doses of rATG on rejections and infection rates. MATERIAL AND METHODS:
      This was a retrospective, single-center chart review that included 142 renal
      transplant patients from January 2007 to October 2012 who received either 3 or 5
      doses of rATG. RESULTS: The primary outcome of biopsy-proven acute rejection
      (BPAR) was not significantly different between the 3-dose and 5-dose groups,
      (6.1% versus 7.4%, p=NS). No significant difference was seen between the 3-dose
      and 5-dose groups in regards to bacterial infections (33.9% versus 40.7%, p>0.05)
      or BK viremia (24.3% versus 18.5%, p>0.05). However, in regards to CMV viremia
      there was a significantly higher incidence in the 5-dose group (37% versus 15.7%,
      p=0.47). CONCLUSIONS: Five doses of rATG versus 3 doses did not provide any
      additional benefit in preventing BPAR.

PMID- 25994123
TI  - Empowering families by engaging and relating Murri way: a grounded theory study
      of the implementation of the Cape York Baby Basket program.
AB  - BACKGROUND: Evaluating program outcomes without considering how the program was
      implemented can cause misunderstandings and inefficiencies when initiating
      program improvements. In conjunction with a program evaluation, reported
      elsewhere, this paper theorises the process of implementing an Indigenous
      Australian maternal and child health program. The Baby Basket program was
      developed in 2009 for the remote Cape York region and aimed to improve the
      attendance and engagement of Indigenous women at antenatal and postnatal clinics
      through providing three baskets of maternal and baby goods and associated health
      education. METHODS: Constructivist grounded theory methods were used to generate
      and analyse data from qualitative interviews and focus groups with Indigenous
      women who received the baskets, their extended family members, and healthcare
      workers who delivered them. Data was coded in NVivo with concepts iteratively
      compared until higher order constructs and their relationships could be modelled
      to explain the common purpose for participants, the process involved in achieving
      that purpose, key strategies, conditions and outcomes. Theoretical terms are
      italicised. RESULTS: Program implementation entailed empowering families through
      a process of engaging and relating Murri (Queensland Indigenous) way. Key
      influencing conditions of the social environment were the remoteness of
      communities, keeping up with demand, families' knowledge, skills and roles and
      organisational service approaches and capacities. Engaging and relating Murri way
      occurred through four strategies: connecting through practical support, creating
      a culturally safe practice, becoming informed and informing others, and linking
      at the clinic. These strategies resulted in women and families taking
      responsibility for health through making healthy choices, becoming empowered
      health consumers and advocating for community changes. CONCLUSIONS: The
      theoretical model was applied to improve and revise Baby Basket program
      implementation, including increased recognition of the importance of empowering
      families by extending the home visiting approach up to the child's third
      birthday. Engaging and relating Murri way was strengthened by formal recognition
      and training of Indigenous health workers as program leaders. This theoretical
      model of program implementation was therefore useful for guiding program
      improvements, and could be applicable to other Indigenous maternal and child
      health programs.

PMID- 25994124
TI  - Structure and vascularization of the ventricular myocardium in Holocephali: their
      evolutionary significance.
AB  - It was generally assumed that the ventricle of the primitive vertebrate heart was
      composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal
      blood. In addition, it was presumed that the mixed ventricular myocardium,
      consisting of a compacta and a spongiosa, and its supply through coronary
      arteries appeared several times throughout fish evolution. Recent work has
      suggested, however, that a fully vascularized, mixed myocardium may be the
      primitive condition in gnathostomes. The present study of the heart ventricles of
      four holocephalan species aimed to clarify this controversy. Our observations
      showed that the ventricular myocardium of Chimaera monstrosa and Harriotta
      raleighana consists of a very thin compacta overlying a widespread spongiosa. The
      ventricle of Hydrolagus affinis is composed exclusively of trabeculated
      myocardium. In these three species there is a well-developed coronary artery
      system. The main coronary artery trunks run along the outflow tract, giving off
      subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated
      by branches of the subepicardial arteries and by penetrating arterial vessels
      arising directly from the main coronary trunks at the level of the
      conoventricular junction. The ventricle of Rhinochimaera atlantica has only
      spongy myocardium supplied by luminal blood. Small coronary arterial vessels are
      present in the subepicardium, but they do not enter the myocardial trabeculae.
      The present findings show for the first time that in a wild living vertebrate
      species, specifically H. affinis, an extensive coronary artery system supplying
      the whole cardiac ventricle exists in the absence of a well-developed compact
      ventricular myocardium. This is consistent with the notion derived from
      experimental work that myocardial cell proliferation and coronary vascular growth
      rely on distinct developmental programs. Our observations, together with data in
      the literature on elasmobranchs, support the view that the mixed ventricular
      myocardium is primitive for chondrichthyans. The reduction or even lack of
      compacta in holocephali has to be regarded as a derived anatomical trait. Our
      findings also fit in with the view that the mixed myocardium was the primitive
      condition in gnathostomes, and that the absence of compact ventricular myocardium
      in different actinopterygian groups is the result of a repeated loss of such type
      of cardiac muscle during fish evolution. 

PMID- 25994125
TI  - Polypterus and the evolution of fish pectoral musculature.
AB  - Polypterus, a member of the most primitive living group of ray-finned fishes, has
      demonstrated the ability to perform fin-assisted terrestrial locomotion, a
      behavior that indicates a complex pectoral musculoskeletal system. Review of the
      literature reveals that many aspects of the pectoral muscular anatomy of
      Polypterus are still unclear, with a number of conflicting descriptions. We
      provide a new interpretation of the pectoral musculature using soft tissue
      enhanced microCT scanning and gross anatomical dissection. The results
      demonstrate a complex musculature, with six independent muscles crossing the
      glenoid-fin joint. Comparisons with other bony-fish (Osteichthyes), including
      both ray-finned (Actinopterygii) and lobed-fin (Sarcopterygii) fish, indicate the
      presence of novel muscles within Polypterus: coracometapterygialis I+II and the
      zonopropterygialis medialis. Examination of these muscular additions in the
      context of osteichthyan phylogeny indicates that this represents a previously
      unrecognized event in the evolution of pectoral musculature in Osteichthyes.
      Despite its phylogenetic position as a basal actinopterygian, the musculature of
      Polypterus has more similarities both anatomically and functionally with that of
      sarcopterygians. This anatomy, along with other features of Polypterus anatomy
      such as lobed fins, ventral paired lungs, and a large spiracle, may make it a
      good model for inferences of stem tetrapod locomotion. 

PMID- 25994126
TI  - Sympathetic innervation of human muscle spindles.
AB  - The aim of the present study was to investigate the presence of sympathetic
      innervation in human muscle spindles, using antibodies against neuropeptide Y
      (NPY), NPY receptors and tyrosine hydroxylase (TH). A total of 232 muscle
      spindles were immunohistochemically examined. NPY and NPY receptors were found on
      the intrafusal fibers, on the blood vessels supplying muscle spindles and on free
      nerve endings in the periaxial space. TH-immunoreactivity was present mainly in
      the spindle nerve and vessel. This is, to our knowledge, the first morphological
      study concerning the sympathetic innervation of the human muscle spindles. The
      results provide anatomical evidence for direct sympathetic innervation of the
      intrafusal fibers and show that sympathetic innervation is not restricted to the
      blood vessels supplying spindles. Knowledge about direct sympathetic innervation
      of the muscle spindle might expand our understanding of motor and proprioceptive
      dysfunction under stress conditions, for example, chronic muscle pain syndromes. 

PMID- 25994127
TI  - Occipital foramina development involves localised regulation of mesenchyme
      proliferation and is independent of apoptosis.
AB  - Cranial foramina are holes within the skull, formed during development, allowing
      entry and exit of blood vessels and nerves. Once formed they must remain open,
      due to the vital structures they contain, i.e. optic nerves, jugular vein,
      carotid artery, and other cranial nerves and blood vessels. Understanding cranial
      foramina development is essential as cranial malformations lead to the stenosis
      or complete closure of these structures, resulting in blindness, deafness, facial
      paralysis, raised intracranial pressure and lethality. Here we focus on
      describing early events in the formation of the jugular, carotid and hypoglossal
      cranial foramina that form in the mesoderm-derived, endochondral occipital bones
      at the base of the embryonic chick skull. Whole-mount skeletal staining of skulls
      indicates the appearance of these foramina from HH32/D7.5 onwards. Haematoxylin &
      eosin staining of sections shows that the intimately associated mesenchyme,
      neighbouring the contents of these cranial foramina, is initially very dense and
      gradually becomes sparser as development proceeds. Histological examination also
      revealed that these foramina initially contain relatively large-diameter nerves,
      which later become refined, and are closely associated with the blood vessel,
      which they also innervate within the confines of the foramina. Interestingly
      cranial foramina in the base of the skull contain blood vessels lacking smooth
      muscle actin, which suggests these blood vessels belong to glomus body structures
      within the foramina. The blood vessel shape also appears to dictate the overall
      shape of the resulting foramina. We initially hypothesised that cranial foramina
      development could involve targeted proliferation and local apoptosis to cause
      'mesenchymal clearing' and the creation of cavities in a mechanism similar to
      joint cavitation. We find that this is not the case, and propose that a mechanism
      reliant upon local nerve/blood vessel-derived restriction of ossification may
      contribute to foramina formation during cranial development. 

PMID- 25994128
TI  - Do constraints associated with the locomotor habitat drive the evolution of
      forelimb shape? A case study in musteloid carnivorans.
AB  - Convergence in morphology can result from evolutionary adaptations in species
      living in environments with similar selective pressures. Here, we investigate
      whether the shape of the forelimb long bones has converged in environments
      imposing similar functional constraints, using musteloid carnivores as a model.
      The limbs of quadrupeds are subjected to many factors that may influence their
      shape. They need to support body mass without collapsing or breaking, yet at the
      same time resist the stresses and strains induced by locomotion. This likely
      imposes strong constraints on their morphology. Our geometric morphometric
      analyses show that locomotion, body mass and phylogeny all influence the shape of
      the forelimb. Furthermore, we find a remarkable convergence between: (i) aquatic
      and semi-fossorial species, both displaying a robust forelimb, with a shape that
      improves stability and load transfer in response to the physical resistance
      imposed by the locomotor environment; and (ii) aquatic and arboreal/semi-arboreal
      species, with both groups displaying a broad capitulum. This augments the degree
      of pronation/supination, an important feature for climbing as well as grasping
      and manipulation ability, behaviors common to aquatic and arboreal species. In
      summary, our results highlight how musteloids with different locomotor ecologies
      show differences in the anatomy of their forelimb bones. Yet, functional demands
      for limb movement through dense media also result in convergence in forelimb long
      bone shape between diverse groups, for example, otters and badgers. 

PMID- 25994129
TI  - Prevalence of HIV and syphilis infections among pregnant women attending
      antenatal clinics in Tanzania, 2011.
AB  - BACKGROUND: The occurrence of HIV-1 and syphilis infections during pregnancy
      poses major health risks to the foetus due to mother-to-child transmission. We
      conducted surveillance of HIV and syphilis infections among pregnant women
      attending antenatal clinics (ANCs) in Mainland Tanzania in 2011. METHODS: This
      surveillance was carried out in 133 ANCs selected from 21 regions in Tanzania. In
      each region, six ANC sites were selected, with urban, semi-urban, and rural areas
      contributing two each. All pregnant women who were attending selected sentinel
      ANC sites for the first time at any pregnancy between September and December 2011
      were enrolled. Serial ELISA assays were performed to detect HIV infection in an
      unlinked anonymous manner using dried blood spot (DBS) after routine syphilis
      testing. Data analysis was conducted using Stata v.12 software. RESULTS: A total
      of 39,698 pregnant women representing 2.4 % of all pregnant women (1.68 million)
      attending ANCs in the Mainland Tanzania were enrolled. The overall HIV prevalence
      was found to be 5.6 % (95 % CI: 5.4-5.8 %). The risk for HIV infection was
      significantly higher among women aged 25-34 (cOR = 1.97, 95 % CI: 1.79-2.16; p <
      0.05), older than 35 years (cOR = 1.88, 95 % CI: 1.62-2.17; p < 0.05) and those
      having 1-2 and 3-4 previous pregnancies. HIV infection was less prevalent among
      women attending rural ANC clinics (cOR = 0.46, 95 % CI 0.4-0.52; p < 0.05). The
      overall syphilis prevalence was 2.5 % (95 % CI: 2.3, 3.6). The risk for syphilis
      infection was significantly higher among women attending semi-urban and rural
      clinics and those having 3-4, and 5 previous pregnancies (p < 0.05). Marital
      status and level of education were not statistically significant with either of
      the two infections. HIV and syphilis co-infections occurred in 109 of 38,928 (0.3
      %). CONCLUSION: The overall prevalence of HIV infection (5.6 %) and syphilis (2.5
      %) found among pregnant women attending ANC clinics in Tanzania calls for further
      strengthening of current intervention measures, which include scaling up the
      integration of prevention of mother to child transmission (PMTCT) services in
      Reproductive and Child Health (RCH) clinics.

PMID- 25994130
TI  - Infarcted Left Ventricles Have Stiffer Material Properties and Lower Stiffness
      Variation: Three-Dimensional Echo-Based Modeling to Quantify In Vivo Ventricle
      Material Properties.
AB  - Methods to quantify ventricle material properties noninvasively using in vivo
      data are of great important in clinical applications. An ultrasound echo-based
      computational modeling approach was proposed to quantify left ventricle (LV)
      material properties, curvature, and stress/strain conditions and find differences
      between normal LV and LV with infarct. Echo image data were acquired from five
      patients with myocardial infarction (I-Group) and five healthy volunteers as
      control (H-Group). Finite element models were constructed to obtain ventricle
      stress and strain conditions. Material stiffening and softening were used to
      model ventricle active contraction and relaxation. Systolic and diastolic
      material parameter values were obtained by adjusting the models to match echo
      volume data. Young's modulus (YM) value was obtained for each material stress
      strain curve for easy comparison. LV wall thickness, circumferential and
      longitudinal curvatures (C- and L-curvature), material parameter values, and
      stress/strain values were recorded for analysis. Using the mean value of H-Group
      as the base value, at end-diastole, I-Group mean YM value for the fiber direction
      stress-strain curve was 54% stiffer than that of H-Group (136.24 kPa versus 88.68
      kPa). At end-systole, the mean YM values from the two groups were similar (175.84
      kPa versus 200.2 kPa). More interestingly, H-Group end-systole mean YM was 126%
      higher that its end-diastole value, while I-Group end-systole mean YM was only
      29% higher that its end-diastole value. This indicated that H-Group had much
      greater systole-diastole material stiffness variations. At beginning-of-ejection
      (BE), LV ejection fraction (LVEF) showed positive correlation with C-curvature,
      stress, and strain, and negative correlation with LV volume, respectively. At
      beginning-of-filling (BF), LVEF showed positive correlation with C-curvature and
      strain, but negative correlation with stress and LV volume, respectively. Using
      averaged values of two groups at BE, I-Group stress, strain, and wall thickness
      were 32%, 29%, and 18% lower (thinner), respectively, compared to those of H
      Group. L-curvature from I-Group was 61% higher than that from H-Group. Difference
      in C-curvature between the two groups was not statistically significant. Our
      results indicated that our modeling approach has the potential to determine in
      vivo ventricle material properties, which in turn could lead to methods to infer
      presence of infarct from LV contractibility and material stiffness variations.
      Quantitative differences in LV volume, curvatures, stress, strain, and wall
      thickness between the two groups were provided.

PMID- 25994131
TI  - Comparative genome analysis of Pseudogymnoascus spp. reveals primarily clonal
      evolution with small genome fragments exchanged between lineages.
AB  - BACKGROUND: Pseudogymnoascus spp. is a wide group of fungi lineages in the family
      Pseudorotiaceae including an aggressive pathogen of bats P. destructans. Although
      several lineages of P. spp. were shown to produce ascospores in culture, the vast
      majority of P. spp. demonstrates no evidence of sexual reproduction. P. spp. can
      tolerate a wide range of different temperatures and salinities and can survive
      even in permafrost layer. Adaptability of P. spp. to different environments is
      accompanied by extremely variable morphology and physiology. RESULTS: We
      sequenced genotypes of 14 strains of P. spp., 5 of which were extracted from
      permafrost, 1 from a cryopeg, a layer of unfrozen ground in permafrost, and 8
      from temperate surface environments. All sequenced genotypes are haploid.
      Nucleotide diversity among these genomes is very high, with a typical
      evolutionary distance at synonymous sites dS ~ 0.5, suggesting that the last
      common ancestor of these strains lived >50 Mya. The strains extracted from
      permafrost do not form a separate clade. Instead, each permafrost strain has
      close relatives from temperate environments. We observed a strictly clonal
      population structure with no conflicting topologies for ~99% of genome sequences.
      However, there is a number of short (~100-10,000 nt) genomic segments with the
      total length of 67.6 Kb which possess phylogenetic patterns strikingly different
      from the rest of the genome. The most remarkable case is a MAT-locus, which has 2
      distinct alleles interspersed along the whole-genome phylogenetic tree.
      CONCLUSIONS: Predominantly clonal structure of genome sequences is consistent
      with the observations that sexual reproduction is rare in P. spp. Small number of
      regions with noncanonical phylogenies seem to arise due to some recombination
      events between derived lineages of P. spp., with MAT-locus being transferred on
      multiple occasions. All sequenced strains have heterothallic configuration of MAT
      locus.

PMID- 25994132
TI  - The long noncoding RNA HOTAIR has tissue and cell type-dependent effects on HOX
      gene expression and phenotype of urothelial cancer cells.
AB  - BACKGROUND: Urothelial carcinoma (UC) is the fifth most common cancer in the
      developed world. Delineation of differentiation subtypes in UC highlighted the
      importance of aberrant differentiation. Understanding underlying mechanisms may
      facilitate diagnosis and development of efficient therapy strategies. It is well
      accepted that epigenetic mechanisms are involved. Long noncoding RNAs (lncRNAs),
      a new class of epigenetic factors, are thought to mediate molecular differences
      between cell types to control cellular identity. The present study focuses on the
      lncRNA HOTAIR, originating from the HOXC locus. Its overexpression induces an
      aggressive phenotype in many cancers and aberrant expression of homeotic HOX
      transcription factors, especially HOXD10, that regulate differentiation and
      tissue homeostasis. The aim of the present study was to determine the functional
      role of HOTAIR in UC with regard to aggressive phenotype, regulation of aberrant
      differentiation and altered HOX gene expression. METHODS: We determined RNA
      expression levels of HOTAIR and HOX genes in UC tissues and cell lines. Knockdown
      of HOTAIR and ectopic overexpression was performed to determine the effect on
      reported target genes in UC. Cell lines were stably transfected with HOTAIR to
      investigate changes in phenotype and HOX gene expression. RESULTS: HOTAIR was
      overexpressed in approximately half of UC tissues and cell lines. Effects of
      HOTAIR overexpression differed between cell lines. Whereas VM-CUB1 cells acquired
      the expected phenotype with increased proliferation, clonogenicity, anchorage
      independent growth, migratory activity and epithelial-to-mesenchymal transition,
      5637 cells grew more slowly displaying induction of senescence and related immune
      response genes. Other UC lines showed intermediate effects. Expression profiling
      revealed divergent effects on HOX genes, cell cycle regulators and
      differentiation according with the phenotypic differences between HOTAIR
      overexpressing VM-CUB1 and 5637 cells. CONCLUSIONS: Our data indicate that HOTAIR
      overexpression may affect differentiation state and aggressiveness of UC cells,
      but in a cell-type dependent manner. Our functional studies and the comparison of
      our expression data sets with those from other cancer cell types, which revealed
      minimal overlaps, indicate that effects of HOTAIR are strongly tissue-dependent
      and can even differ within one cancer type. Thus, HOTAIR functions and target
      genes cannot simply be transferred from one cancer type to the other.

PMID- 25994133
TI  - Impact of exercise and vitamin B1 intake on hippocampal brain-derived
      neurotrophic factor and spatial memory performance in a rat model of stress.
AB  - Chronic stress affects brain areas involved in learning and emotional responses
      through modulation of neurotropic factors or neurotransmitters. Therefore, we
      investigated the role of exercise and thiamine supplementation on spatial memory
      and on brain-derived neurotrophic factor (BDNF) and acetylcholine (Ach) content
      in the hippocampus of the stressed animals. Male Wistar rats were randomly
      assigned to 4 groups (8 rats/group): control group; stress group; swimming and
      stress group; and thiamine and stress group. All animals were assessed by a T
      maze for spatial memory or open field test for locomotion and anxiety. BDNF and
      Ach were estimated in the hippocampus. Chronic immobilization stress resulted in
      a significant decrease in BDNF and Ach levels in the hippocampus and impairment
      in spatial memory functions and decreased basal activity. However, either
      swimming training or thiamine intake for 30 d was proved to induce a significant
      increase both in BDNF and Ach in conjunction with improved performance in the T
      maze, marked anxiolytic effect and enhanced ambulation in the open field test, as
      compared to the stress group. Interestingly, swimming-exercised rats showed
      significantly higher levels of BDNF versus thiamine-receiving rats, while
      thiamine-receiving rats showed higher locomotor activity and less freezing
      behavior in the open field test compared to the swimming group. It was concluded
      that decreased BDNF and Ach after stress exposure could be a mechanism for the
      deleterious actions of stress on memory function; swimming exercise or vitamin B1
      supplementation for 30 d was a protective tool to improve coping with chronic
      stress by modulating BDNF and Ach content along with enhancement of memory
      functions and motor activities. 

PMID- 25994134
TI  - Synthesis and properties of formylcobalamin and propionylcobalamin, novel
      acylcobalamins.
AB  - Formylcobalamin (formyl-Cbl), a C1-unit carrying corrinoid, and
      propionylcobalamin (propionyl-Cbl) were synthesized for the first time, and their
      properties were compared with those of acetylcobalamin (acetyl-Cbl). Formyl-Cbl,
      acetyl-Cbl, and propionyl-Cbl were decomposed by a NH2OH treatment, forming formo
      , aceto-, and propionohydroxamic acids, respectively, which offers a proof for
      the presence of "activated" acyl groups and for their structures of Co-acyl-Cbls.
      These results, together with chromatographic, electrophoretic, and spectroscopic
      properties, indicate that the acyl-Cbls synthesized are actually formyl-Cbl,
      acetyl-Cbl, and propionyl-Cbl. Spectroscopic and electrophoretic properties were
      consistent with the sigma-donor strength or trans-effect increasing in the order:
      formyl<acetyl<propionyl. All acyl-Cbls underwent the Co-C bond cleavage upon
      photo-irradiation with a tungsten light bulb as well as upon treatment with
      alkali, forming aquacobalamin (aqCbl) and hydroxocobalamin (OH-Cbl),
      respectively, under air. Formyl-Cbl was thermally unstable and decomposed to
      aqCbl, and the thermal stability in neutral solution was much lower than in
      diluted HCl. In contrast, acetyl-Cbl and propionyl-Cbl were heat-stable under
      these conditions. Formyl-Cbl was essentially unsusceptible to unbufferized KCN
      solution, although acetyl-Cbl and propionyl-Cbl were rapidly converted to
      dicyanocobalamin under the same conditions. Such abnormal behaviors of formyl-Cbl
      suggest that it mainly exists in a hydrated form as formaldehyde.

PMID- 25994135
TI  - Effects of sugar-sweetened beverage intake on the development of type 2 diabetes
      mellitus in subjects with impaired glucose tolerance: the Mihama diabetes
      prevention study.
AB  - In Japan, the incidence of type 2 diabetes mellitus (T2DM) is increasing for
      several reasons, including increased consumption of sugar-sweetened beverages
      (SSBs). However, whether SSBs cause T2DM by excess of energy production resulting
      in obesity remains unclear. Therefore, the present study was designed to evaluate
      the effects of SSB intake on the development of T2DM in subjects with impaired
      glucose tolerance (IGT). Ninety-three subjects (30 males and 63 females) with IGT
      aged 40-69 y and residing in the Mihama district (southern Mie Prefecture, Japan)
      were included in the study. The mean observational period was 3.6 y. All subjects
      underwent the 75-g oral glucose tolerance test (OGTT) and completed a lifestyle
      questionnaire survey related to SSB intake. OGTT results and SSB intake were
      evaluated before and after the observational period. In addition, the correlation
      between SSB intake and development of T2DM was investigated. Of the 93 subjects,
      20 (21.5%) developed T2DM (T2DM group) and demonstrated a significantly high SSB
      intake compared with the group that did not develop the disease (non-T2DM group).
      The odds ratio for the incidence of T2DM based on SSB intake was 3.26 (95%
      confidence interval, 1.17-9.06). The body mass index (BMI; kg/m(2)) and the
      homeostasis model assessment for insulin resistance (HOMA-R) values was
      significantly higher in the T2DM group than in the non-T2DM group, while the
      insulinogenic indices were significantly lower in the former than in the latter
      group. The sum of insulin secretion levels during OGTT was not significantly
      different between groups. SSB intake correlated with the predisposition for
      developing T2DM, possibly by influencing body weight, insulin resistance, and the
      ability of the pancreatic beta cells to effectively compensate for the insulin
      resistance. 

PMID- 25994136
TI  - A long-term high-fat diet changes iron distribution in the body, increasing iron
      accumulation specifically in the mouse spleen.
AB  - Although iron is an essential trace metal, its presence in excess causes
      oxidative stress in the human body. Recent studies have indicated that iron
      storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction
      or iron chelation ameliorates symptoms of type 2 diabetes in mouse models.
      However, whether iron content in the body changes with the development of
      diabetes is unknown. Here, we investigated the dynamics of iron accumulation and
      changes in iron absorption-related genes in mice that developed obesity and
      diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk)
      were compared with control mice for hematologic features, serum ferritin levels,
      and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis,
      liver, duodenum, and spleen. In addition, the spleen was examined histologically.
      Iron absorption-related gene expression in the liver and duodenum was also
      examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice.
      The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or
      liver. Increased percentages of the splenic red pulp and macrophages were
      observed in HFD-fed mice and iron accumulation in the spleen was found mainly in
      the splenic red pulp. The HFD-fed mice also showed decreased iron content in the
      duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron
      absorption-related gene, was elevated in the duodenum of HFD-fed mice. These
      results indicate that iron accumulation (specifically accumulation in the spleen)
      is enhanced by the development of type 2 diabetes induced by HFD. 

PMID- 25994137
TI  - Putative PPAR target genes express highly in skeletal muscle of insulin-resistant
      MetS model SHR/NDmc-cp rats.
AB  - It is known that insulin resistance in skeletal muscle induces subsequent
      metabolic diseases such as metabolic syndrome (MetS). However, which genes are
      altered in the skeletal muscle by development of insulin resistance in animal
      models has not been examined. In this study, we performed microarray and
      subsequent real-time RT-PCR analyses using total RNA extracted from the
      gastrocnemius muscle of the MetS model, spontaneously hypertensive corpulent
      congenic (SHR/NDmc-cp) rats, and control Wistar Kyoto (WKY) rats. SHR/NDmc-cp
      rats displayed overt insulin resistance relative to WKY rats. The expression of
      many genes related to fatty acid oxidation was higher in SHR/NDmc-cp rats than in
      WKY rats. Among 18 upregulated genes, putative peroxisome proliferator responsive
      elements were found in the upstream region of 15 genes. The protein expression of
      ACOX2, an upregulated gene, and peroxisome proliferator-activated receptor (PPAR)
      G1, but not of PPARG2, PPARA or PPARD, was higher in the gastrocnemius muscle of
      SHR/NDmc-cp rats than that in WKY rats. These results suggest that insulin
      resistance in the MetS model, SHR/NDmc-cp rats, is positively associated with the
      expression of fatty acid oxidation-related genes, which are presumably PPARs'
      targets, in skeletal muscle.

PMID- 25994138
TI  - Colloidal submicron-particle curcumin exhibits high absorption efficiency-a
      double-blind, 3-way crossover study.
AB  - Curcumin is a major constituent of the spice turmeric and has various biological
      activities, including anticancer, antioxidant, and anti-inflammatory properties,
      as well as alcohol detoxification. However, because of its poor absorption
      efficiency, it is difficult for orally administered curcumin to reach blood
      levels sufficient to exert its bioactivities. To overcome this problem, several
      curcumin preparations with a drug-delivery system (DDS) have been developed to
      increase the bioavailability of curcumin after oral administration, and tested as
      functional foods and potential medical agents in humans. We have also produced
      capsules containing Theracurmin, curcumin dispersed with colloidal submicron
      particles. To evaluate the absorption efficiency of three types of DDS curcumin,
      we performed a double-blind, 3-way crossover study. We compared plasma curcumin
      levels after the administration of Theracurmin and 2 other capsule types of
      curcumin with DDS, BCM-95 (micronized curcumin with turmeric essential oils) and
      Meriva (curcumin-phospholipid). Nine healthy subjects (male/female=5/4, age: 24
      32 y old) were administered these 3 preparations of DDS curcumin, at commonly
      used dosages. Six capsules of Theracurmin, 1 capsule of BCM-95, and 2 capsules of
      Meriva contain 182.4 +/- 1.0, 279.3 +/- 10.7, and 152.5 +/- 20.3 mg of curcumin,
      respectively. The maximal plasma curcumin concentration (0-24 h) of Theracurmin
      was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively.
      Moreover, the area under the blood concentration-time curve at 0-24 h was found
      to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva,
      respectively. These data indicate that Theracurmin exhibits a much higher
      absorption efficiency than other curcumin DDS preparations.

PMID- 25994140
TI  - Association between the frequency of meals combining "Shushoku, Shusai, and
      Hukusai" (Staple food, main dish, and side dish) and intake of nutrients and food
      groups among Japanese young adults aged 18-24 years: a cross-sectional study.
AB  - "Shushoku," "Shusai," and "Hukusai" are staple food, main dish, and side dish,
      respectively. The recommended meal in Japan is a combination of "Shushoku,"
      "Shusai," and "Hukusai"; however, it remains unclear whether there is an
      association between the frequency of these meals and intake of nutrients and food
      groups. This cross-sectional study examined the association between the frequency
      of meals combining "Shushoku, Shusai, and Hukusai" and intake of nutrients and
      food groups among 664 Japanese young adults aged 18-24 y. The dietary habits of
      the subjects during the preceding month were assessed using a validated brief
      type self-administered diet history questionnaire. The frequency of meals
      combining "Shushoku, Shusai, and Hukusai" was self-reported according to four
      categories: "less than 1 d or 1 d/wk," "2 or 3 d/wk," "4 or 5 d/wk," and "every
      day." In both women and men, there was an association between the higher
      frequency of these meals and higher intake of the following food groups: pulses,
      green and yellow vegetables, other vegetables, mushrooms, seaweeds, fish and
      shellfish, and eggs. Moreover, there was an association with higher intake of
      protein, polyunsaturated fat, n-6 and n-3 polyunsaturated fat, total dietary
      fiber, soluble and insoluble dietary fiber, beta-carotene, alpha-tocopherol,
      vitamin K, thiamin, riboflavin, folate, pantothenic acid, vitamin C, potassium,
      calcium, magnesium, iron, and copper, and lower intake of carbohydrate in both
      women and men. Our findings support the hypothesis that the meals combining
      "Shushoku, Shusai, and Hukusai" may be associated with intake of many food groups
      and nutrients among Japanese young adults. 

PMID- 25994139
TI  - Impact of physical activity and cardiovascular fitness on total homocysteine
      concentrations in European adolescents: The HELENA study.
AB  - We examined the association of physical activity (PA), cardiovascular fitness
      (CVF) and fatness with total homocysteine (tHcy) concentrations in European
      adolescents. The present study comprised 713 European adolescents aged 14.8 +/-
      1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was
      assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by
      skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and
      tHcy concentrations were measured. To examine the association of tHcy with PA,
      CVF, and fatness after controlling for a set of confounders including age,
      maturity, folate, cobalamin, creatinine, smoking, supplement use, and
      methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%),
      bivariate correlations followed by multiple regression models were performed. In
      the bivariate correlation analysis, tHcy concentrations were slightly negatively
      correlated (p<0.05) with CVF in females (measured both by stages: r=-0.118 and by
      VO2max: r=-0.102) and positively with body mass index (r=0.100). However, daily
      time spent with moderate and vigorous PA showed a weak positive association with
      tHcy in females (p<0.05). tHcy concentrations showed a tendency to decrease with
      increasing CVF and increase with increasing BMI in female European adolescents.
      However, tHcy concentrations were positively associated with moderate and
      vigorous PA in female European adolescents.

PMID- 25994141
TI  - Dietary ribonucleic acid suppresses inflammation of adipose tissue and improves
      glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high
      fat diet.
AB  - Recent evidence suggests that immune cells play an important role in
      differentiation of inflammatory macrophages in adipose tissue, which contributes
      to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown
      to modulate immune function. We hypothesized that RNA affects immune cell
      function in adipose tissue and then improves inflammatory response in adipose
      tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on
      a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk.
      An oral glucose tolerance test was performed. Supplementation of dietary RNA in
      C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC)
      after oral glucose administration than that for control mice. The mRNA expression
      levels of inflammation-related cytokines in adipose tissue and serum interleukin
      6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of
      the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG
      1 knockout mice. These results indicate that RNA improves inflammation in adipose
      tissue and reduces the AUC value following oral glucose administration in a T and
      B cell-dependent manner. 

PMID- 25994142
TI  - Kaempferia parviflora extract increases whole-body energy expenditure in humans:
      roles of brown adipose tissue.
AB  - Kaempferia parviflora extract (KP) has been reported to have a preventive effect
      on obesity in mice, probably by increasing energy expenditure (EE). The aims of
      the current study were to examine the acute effects of KP ingestion on whole-body
      EE in humans and to analyze its relation to the activity of brown adipose tissue
      (BAT), a site of non-shivering thermogenesis. After an oral ingestion of an
      ethanol extract of KP, EE increased significantly, showing a maximal increase of
      229+/-69 kJ/d at 60 min, while it did not change after placebo ingestion. To
      evaluate BAT activity, the subjects underwent fluorodeoxyglucose-positron
      emission tomography, and divided into two groups with high- and low-BAT
      activities. A similar and greater response of EE to KP ingestion was observed in
      the high-BAT group (351+/-50 kJ/d at 60 min), but not in the low activity group.
      Placebo ingestion did not cause any significant EE change in either group. These
      results indicate that a single oral ingestion of the KP extract can potentially
      increase whole-body EE probably through the activation of BAT in healthy men, and
      may be useful as an anti-obesity regimen. 

PMID- 25994143
TI  - Anticoagulating effects of water-extractive components from heshiko and
      narezushi, Japanese fermented aquatic products.
AB  - Antithrombotic effects of water-extractive components (extracts) from heshiko and
      narezushi, traditional fermented aquatic products in Japan, were investigated in
      terms of blood coagulation and fibrinolysis by means of animal experiments. Blood
      clot formation was suppressed by administration of heshiko and narezushi extracts
      to both groups of Wistar rats fed artificial and high-fat experimental diets.
      Prothrombin time and activated partial thromboplastin time of plasma prepared
      from the rats, as indices of blood coagulation, were not prolonged by
      administration of heshiko or narezushi extracts. In contrast, the activities of
      plasmin and tissue plasminogen activator (tPA), key enzymes in the fibrinolytic
      system, were significantly increased by administration of heshiko and narezushi
      extracts. These results suggest that the anticoagulating effects of heshiko and
      narezushi extracts are associated with the promotion of the fibrinolytic system
      via enhancement of plasmin and tPA activities. 

PMID- 25994144
TI  - Young persimmon ingestion suppresses lipid oxidation in rats.
AB  - Persimmon is widely eaten in Asia and the nutritional components of young and
      mature persimmons differ. Although raw young persimmon has a strong bitter taste
      and is difficult to eat, the beneficial health effects of young persimmon powder
      have attracted attention in recent years. Young persimmon has been suggested to
      have hypolipidemic activity as well as other biological effects. However, there
      has been little investigation of the beneficial effects of young persimmon. In
      the present study, we investigated the antioxidative effects of persimmon in an
      animal study and compared the effects of young persimmon and mature persimmon.
      Six-week-old male F344 rats were divided into three groups and fed a standard
      diet, young persimmon diet, or mature persimmon diet for 4 wk. The young
      persimmon and mature persimmon groups were fed a diet containing 5% (w/w) freeze
      dried young or mature persimmon. We analyzed phosphatidylcholine hydroperoxide
      (PCOOH) levels in the rats as a biomarker of membrane lipid peroxidation. Our
      study showed that plasma PCOOH levels were significantly lower in the young
      persimmon group (36.1 +/- 28.5 pmol/mL plasma) than in the control group (120 +/-
      66 pmol/mL plasma). No significant difference was observed between the mature
      persimmon group (57.3 +/- 15.6 pmol/mL plasma) and the control group. It is
      possible that ascorbic acid and soluble tannin contribute to the difference in
      the antioxidant effects of young and mature persimmons. These results indicated
      that intake of young persimmon contributes to the reduction of plasma
      phospholipid hydroperoxide levels in rats.

PMID- 25994145
TI  - Influence of Treatment with Extracts of Hypsyzigus marmoreus Mushroom on Body
      Composition during Obesity Development in KK-A(y) Mice.
AB  - Hypsyzigus marmoreus (HM), an edible mushroom, has several effects, including
      antitumor, antioxidant and anti-allergy properties. On the other hand, the
      possibly useful effect of HM in diabetic mice has not as yet been elucidated. In
      this study, we showed treatment with a water soluble extract from HM (EHM) to
      reduce fat deposits without affecting body weight loss in KK-A(y) mice. EHM
      treatment also abolished the expressions of pro-inflammatory adipokines, such as
      tumor necrosis factor alpha and monocyte chemoattractant protein 1, as compared
      with vehicle treatment. The expressions of uncoupling protein 3 and peroxisome
      proliferator-activated receptor gamma coactivator 1alpha in the soleus muscles of
      EHM treatment groups were significantly elevated as compared to those in vehicle
      treated muscle tissues. These results raise the possibility that EHM can regulate
      both obesity and insulin resistance. 

PMID- 25994146
TI  - Rapid and simple purification of lysozyme from the egg shell membrane.
AB  - Lysozyme (EC 3.2.1.17) is a hydrolytic enzyme that cleaves the beta-(1,4)
      glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in
      peptidoglycan, a major bacterial cell wall polymer. In the food industry,
      lysozyme is used as an additive mainly in the production of wine and beer.
      Lysozyme was found to be localized in the egg shell membrane. In this study, we
      found that lysozyme was easily purified from the egg shell membrane and that the
      enzyme also had antibacterial activity. Furthermore, we found that the
      antibacterial activity of purified lysozyme from the egg shell membrane was lower
      than that of purified lysozyme from the egg white at alkaline pH. The method for
      rapid purification of lysozyme developed in this study should contribute to the
      food industry. 

PMID- 25994148
TI  - Split-alignment of genomes finds orthologies more accurately.
AB  - We present a new pair-wise genome alignment method, based on a simple concept of
      finding an optimal set of local alignments. It gains accuracy by not masking
      repeats, and by using a statistical model to quantify the (un)ambiguity of each
      alignment part. Compared to previous animal genome alignments, it aligns
      thousands of locations differently and with much higher similarity, strongly
      suggesting that the previous alignments are non-orthologous. The previous methods
      suffer from an overly-strong assumption of long un-rearranged blocks. The new
      alignments should help find interesting and unusual features, such as fast
      evolving elements and micro-rearrangements, which are confounded by alignment
      errors. 

PMID- 25994147
TI  - Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection
      of rhesus macaques.
AB  - B cell functional defects are associated with delayed neutralizing antibody
      development in pathogenic lentivirus infections. However, the timeframe for
      alterations in the antibody repertoire and somatic hypermutation (SHM) remains
      unclear. Here, we utilized the SIV/rhesus macaque (RM) model to investigate the
      dynamics of immunoglobulin V(H) gene diversity and SHM following infection. Three
      RMs were infected with SIVmac239, and V(H)1, V(H)3, and V(H)4 genes were
      amplified from peripheral blood at 0, 2, 6, 24, and 36 weeks postinfection for
      next-generation sequencing. Analysis of over 3.8 million sequences against
      currently available RM germline V(H) genes revealed a highly biased V(H) gene
      repertoire in outbred RMs. SIV infection did not significantly perturb the
      predominant IgG1 response, but overall immunoglobulin SHM declined during the
      course of SIV infection. Moreover, SHM at the AID deamination hotspot, WRC,
      rapidly decreased and was suppressed throughout SIV infection. In contrast, a
      transient increase in mutations at the APOBEC3G deamination hotspot, CCC,
      coincided with a spike in APOBEC3G expression during acute SIV infection. The
      results outline a timetable for altered V(H) gene repertoire and IgG SHM in the
      SIV/RM model and suggest a burst of APOBEC3G-mediated antibody SHM during acute
      SIV infection.

PMID- 25994150
TI  - MUC4 regulates cellular senescence in head and neck squamous cell carcinoma
      through p16/Rb pathway.

PMID- 25994149
TI  - Neutrophil extracellular trap (NET) formation characterises stable and
      exacerbated COPD and correlates with airflow limitation.
AB  - BACKGROUND: COPD is a progressive disease of the airways that is characterized by
      neutrophilic inflammation, a condition known to promote the excessive formation
      of neutrophil extracellular traps (NETs). The presence of large amounts of NETs
      has recently been demonstrated for a variety of inflammatory lung diseases
      including cystic fibrosis, asthma and exacerbated COPD. OBJECTIVE: We test
      whether excessive NET generation is restricted to exacerbation of COPD or whether
      it also occurs during stable periods of the disease, and whether NET presence and
      amount correlates with the severity of airflow limitation. PATIENTS, MATERIALS
      AND METHODS: Sputum samples from four study groups were examined: COPD patients
      during acute exacerbation, patients with stable disease, and smoking and non
      smoking controls without airflow limitation. Sputum induction followed the
      ECLIPSE protocol. Confocal laser microscopy (CLSM) and electron microscopy were
      used to analyse samples. Immunolabelling and fluorescent DNA staining were
      applied to trace NETs and related marker proteins. CLSM specimens served for
      quantitative evaluation. RESULTS: Sputum of COPD patients is clearly
      characterised by NETs and NET-forming neutrophils. The presence of large amounts
      of NET is associated with disease severity (p < 0.001): over 90 % in exacerbated
      COPD, 45 % in stable COPD, and 25 % in smoking controls, but less than 5% in non
      smokers. Quantification of NET-covered areas in sputum preparations confirms
      these results. CONCLUSIONS: NET formation is not confined to exacerbation but
      also present in stable COPD and correlates with the severity of airflow
      limitation. We infer that NETs are a major contributor to chronic inflammatory
      and lung tissue damage in COPD.

PMID- 25994151
TI  - Gene targeting by TALEN-induced homologous recombination in goats directs
      production of beta-lactoglobulin-free, high-human lactoferrin milk.
AB  - beta-Lactoglobulin (BLG) is a major goat's milk allergen that is absent in human
      milk. Engineered endonucleases, including transcription activator-like effector
      nucleases (TALENs) and zinc-finger nucleases, enable targeted genetic
      modification in livestock. In this study, TALEN-mediated gene knockout followed
      by gene knock-in were used to generate BLG knockout goats as mammary gland
      bioreactors for large-scale production of human lactoferrin (hLF). We introduced
      precise genetic modifications in the goat genome at frequencies of approximately
      13.6% and 6.09% for the first and second sequential targeting, respectively, by
      using targeting vectors that underwent TALEN-induced homologous recombination
      (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression
      or/and decreased BLG levels in milk from heterozygous goats as well as the
      absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated
      targeting events in somatic cells can be transmitted through the germline after
      SCNT. Our result suggests that gene targeting via TALEN-induced HR may expedite
      the production of genetically engineered livestock for agriculture and
      biomedicine. 

PMID- 25994153
TI  - The promise of non-invasive prenatal testing needs to be monitored
      scientifically.

PMID- 25994152
TI  - Prostate cancer mortality in Serbia, 1991-2010: a joinpoint regression analysis.
AB  - BACKGROUND: The aim of this descriptive epidemiological study was to analyze the
      mortality trend of prostate cancer in Serbia (excluding the Kosovo and Metohia)
      from 1991 to 2010. METHODS: The age-standardized prostate cancer mortality rates
      (per 100 000) were calculated by direct standardization, using the World Standard
      Population. Average annual percentage of change (AAPC) and the corresponding 95%
      confidence interval (CI) was computed for trend using the joinpoint regression
      analysis. RESULTS: Significantly increased trend in prostate cancer mortality was
      recorded in Serbia continuously from 1991 to 2010 (AAPC = +2.2, 95% CI = 1.6
      2.9). Mortality rates for prostate cancer showed a significant upward trend in
      all men aged 50 and over: AAPC (95% CI) was +1.9% (0.1-3.8) in aged 50-59 years,
      +1.7% (0.9-2.6) in aged 60-69 years, +2.0% (1.2-2.9) in aged 70-79 years and
      +3.5% (2.4-4.6) in aged 80 years and over. According to comparability test,
      prostate cancer mortality trends in majority of age groups were parallel (final
      selected model failed to reject parallelism, P > 0.05). CONCLUSION: The
      increasing prostate cancer mortality trend implies the need for more effective
      measures of prevention, screening and early diagnosis, as well as prostate cancer
      treatment in Serbia.

PMID- 25994154
TI  - Compound risk: History of traumatic stress predicts posttraumatic stress disorder
      symptoms and severity in sudden cardiac arrest survivors.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) survivors can develop posttraumatic
      stress disorder (PTSD) which is associated with worse clinical outcomes. The
      purpose of this study was to evaluate the prevalence and predictors of PTSD in a
      large sample of SCA survivors. Prior history of psychological trauma and the
      effects of repeated trauma exposure on subsequent PTSD and symptom severity after
      SCA were also explored. METHODS: A retrospective, cross-sectional study of 188
      SCA survivors from the Sudden Cardiac Arrest Association patient registry
      completed an online questionnaire that included measures of PTSD, trauma history,
      sociodemographics, general health, and cardiac history. RESULTS: Sixty-three
      (36.2%) SCA survivors in this sample scored above the clinical cutoff for PTSD.
      Female gender, worse general health, and younger age predicted PTSD symptoms
      after SCA. Additionally, 50.2% of SCA survivors (n = 95) reported a history of
      trauma exposure and 25.4% (n = 48) of the total sample endorsed a traumatic
      stress response to a historic trauma. Results indicated that a traumatic stress
      response to a historic trauma was a stronger predictor of PTSD after SCA (odds
      ratio = 4.77) than all other variables in the model. CONCLUSIONS: PTSD symptoms
      are present in over one-third of SCA survivors. While demographic or health
      history variables predicted PTSD after SCA, a history of traumatic stress
      response to a previous trauma emerged as the strongest predictor of these
      symptoms. Routine assessment and interdisciplinary management are discussed as
      potential ways to expedite survivors' recovery and return to daily living.

PMID- 25994155
TI  - Lateral Subcutaneous Brow Lift: Updated Technique.

PMID- 25994156
TI  - Repeated Assessment and Practice Effects of the Written Symbol Digit Modalities
      Test Using a Short Inter-Test Interval.
AB  - The Symbol Digit Modalities Test (SDMT) is a widely used instrument to assess
      information processing speed, attention, visual scanning, and tracking.
      Considering that repeated evaluations are a common need in neuropsychological
      assessment routines, we explored test-retest reliability and practice effects of
      two alternate SDMT forms with a short inter-assessment interval. A total of 123
      university students completed the written SDMT version in two different time
      points separated by a 150-min interval. Half of the participants accomplished the
      same form in both occasions, while the other half filled different forms.
      Overall, reasonable test-retest reliabilities were found (r = .70), and the
      subjects that completed the same form revealed significant practice effects (p <
      .001, dz = 1.61), which were almost non-existent in those filling different
      forms. These forms were found to be moderately reliable and to elicit a similar
      performance across participants, suggesting their utility in repeated cognitive
      assessments when brief inter-assessment intervals are required. 

PMID- 25994157
TI  - A first case report of diffuse acneiform eruption caused by capecitabine in a
      patient with small-cell neuroendocrine lung carcinoma.
AB  - Capecitabine is a chemotherapeutic agent which is converted to fluorouracil by
      thymidine phosphorylase in human body. It is one of the commonly used agents in
      colorectal and metastatic breast cancers. Hand-foot syndrome is most commonly
      observed adverse effect of capecitabine; however, it has several adverse
      cutaneous and mucosal effects. To the best of our knowledge, no case with
      acneiform eruption has been reported so far. Here, we presented a 54-year-old man
      with development of capecitabine-related acneiform drug eruption. 

PMID- 25994158
TI  - Manganese and iron as structuring parameters of microbial communities in Arctic
      marine sediments from the Baffin Bay.
AB  - The Arctic Baffin Bay between Canada and Greenland is sea ice-covered during the
      majority of the year, restricting primary production to the summer months.
      Sediments receive low amounts of mostly terrestrial- and less marine-derived
      organic matter. To study microbial communities constrained by physicochemical
      conditions changing with distance from land and ocean depth, we applied high
      throughput 16S rRNA gene sequencing and compared sequence diversity with
      biogeochemical parameters in 40 different sediment samples. Samples originated
      from seven cores down to 470 cm below seafloor along a shelf-to-basin transect.
      Bacterial diversity decreased faster with depth in basin than in shelf sediments,
      suggesting higher organic matter content sustained diversity into greater depths.
      All samples were dominated by Betaproteobacteria (mostly order Burkholderiales),
      which were especially abundant in basin sediments with low organic carbon and
      high Mn and Fe pore water concentrations. Strong statistical correlations between
      concentrations of reduced Mn and/or Fe and the relative abundances of
      Betaproteobacteria suggest that this group is involved in metal reduction in
      Baffin Bay sediments. Dehalococcoidia (phylum Chloroflexi) were abundant in all
      samples, especially in shelf sediments with high organic content. This study
      indicates that Mn and/or Fe play important roles structuring microbial
      communities in Arctic sediments poor in organic matter.

PMID- 25994159
TI  - The impact of nectar chemical features on phenotypic variation in two related
      nectar yeasts.
AB  - Floral nectars become easily colonized by microbes, most often species of the
      ascomycetous yeast genus Metschnikowia. Although it is known that nectar
      composition can vary tremendously among plant species, most probably
      corresponding to the nutritional requirements of their main pollinators, far less
      is known about how variation in nectar chemistry affects intraspecific variation
      in nectarivorous yeasts. Because variation in nectar traits probably affects
      growth and abundance of nectar yeasts, nectar yeasts can be expected to display
      large phenotypic variation in order to cope with varying nectar conditions. To
      test this hypothesis, we related variation in the phenotypic landscape of a vast
      collection of nectar-living yeast isolates from two Metschnikowia species (M.
      reukaufii and M. gruessii) to nectar chemical traits using non-linear redundancy
      analyses. Nectar yeasts were collected from 19 plant species from different plant
      families to include as much variation in nectar chemical traits as possible. As
      expected, nectar yeasts displayed large variation in phenotypic traits,
      particularly in traits related to growth performance in carbon sources and
      inhibitors, which was significantly related to the host plant from which they
      were isolated. Total sugar concentration and relative fructose content
      significantly explained the observed variation in the phenotypic profile of the
      investigated yeast species, indicating that sugar concentration and composition
      are the key traits that affect phenotypic variation in nectarivorous yeasts.

PMID- 25994160
TI  - Are the Conventional Commercial Yeast Identification Methods Still Helpful in the
      Era of New Clinical Microbiology Diagnostics? A Meta-Analysis of Their Accuracy.
AB  - Accurate identification of pathogenic species is important for early appropriate
      patient management, but growing diversity of infectious species/strains makes the
      identification of clinical yeasts increasingly difficult. Among conventional
      methods that are commercially available, the API ID32C, AuxaColor, and Vitek 2
      systems are currently the most used systems in routine clinical microbiology. We
      performed a systematic review and meta-analysis to estimate and to compare the
      accuracy of the three systems, in order to assess whether they are still of value
      for the species-level identification of medically relevant yeasts. After adopting
      rigorous selection criteria, we included 26 published studies involving Candida
      and non-Candida yeasts that were tested with the API ID32C (674 isolates),
      AuxaColor (1,740 isolates), and Vitek 2 (2,853 isolates) systems. The random
      effects pooled identification ratios at the species level were 0.89 (95%
      confidence interval [CI], 0.80 to 0.95) for the API ID32C system, 0.89 (95% CI,
      0.83 to 0.93) for the AuxaColor system, and 0.93 (95% CI, 0.89 to 0.96) for the
      Vitek 2 system (P for heterogeneity, 0.255). Overall, the accuracy of studies
      using phenotypic analysis-based comparison methods was comparable to that of
      studies using molecular analysis-based comparison methods. Subanalysis of studies
      conducted on Candida yeasts showed that the Vitek 2 system was significantly more
      accurate (pooled ratio, 0.94 [95% CI, 0.85 to 0.99]) than the API ID32C system
      (pooled ratio, 0.84 [95% CI, 0.61 to 0.99]) and the AuxaColor system (pooled
      ratio, 0.76 [95% CI, 0.67 to 0.84]) with respect to uncommon species (P for
      heterogeneity, <0.05). Subanalysis of studies conducted on non-Candida yeasts
      (i.e., Cryptococcus, Rhodotorula, Saccharomyces, and Trichosporon) revealed
      pooled identification accuracies of >=98% for the Vitek 2, API ID32C (excluding
      Cryptococcus), and AuxaColor (only Rhodotorula) systems, with significant low or
      null levels of heterogeneity (P > 0.05). Nonetheless, clinical microbiologists
      should reconsider the usefulness of these systems, particularly in light of new
      diagnostic tools such as matrix-assisted laser desorption ionization-time of
      flight (MALDI-TOF) mass spectrometry, which allow for considerably shortened
      turnaround times and/or avoid the requirement for additional tests for species
      identity confirmation. 

PMID- 25994161
TI  - Identification and Clinical Significance of Helcococcus kunzii in Human Samples.
AB  - From 2008 to 2013, 39 Helcococcus kunzii strains were collected from human
      clinical specimens (79% from foot ulcers), and 85% of the 39 patients were
      infected. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)
      mass spectrometry and molecular methods accurately identified all isolates. This
      large study of clinical observations confirms the potential pathogenic role of H.
      kunzii. 

PMID- 25994162
TI  - Evaluation of New bioMerieux Chromogenic CPS Media for Detection of Urinary Tract
      Pathogens.
AB  - Four chromogenic media were compared for their ability to detect urinary tract
      pathogens in 299 urine specimens, of which 175 were found positive, allowing the
      growth of 279 microorganisms. After 18 to 24 h of incubation, the CPS ID4, CPSE,
      CPSO (bioMerieux), and UriSelect4 (Bio-Rad) media showed sensitivities of 97.1%,
      99.3%, 99.6%, and 99.6%, respectively. 

PMID- 25994163
TI  - Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a
      Systematic Review and Meta-Analysis.
AB  - The role of interferon gamma release assays (IGRAs), although established for
      identifying latent tuberculosis, is still evolving in the diagnosis of active
      extrapulmonary tuberculosis. We systematically evaluated the diagnostic
      performance of blood- and pleural fluid-based IGRAs in tuberculous pleural
      effusion (TPE). We searched the PubMed and Embase databases for studies
      evaluating the use of commercially available IGRAs on blood and/or pleural fluid
      samples for diagnosing TPE. The quality of the studies included was assessed
      through the QUADAS-2 tool. The pooled estimates of sensitivity and specificity
      with 95% confidence intervals (95% CI) were generated using a bivariate random
      effects model and examined using forest plots and hierarchical summary receiver
      operating characteristic (HSROC) curves. Indeterminate IGRA results were included
      for sensitivity calculations. Heterogeneity was explored through subgroup
      analysis and meta-regression based on prespecified covariates. We identified 19
      studies assessing the T.SPOT.TB and/or QuantiFERON assays. There were 20 and 14
      evaluations, respectively, of whole-blood and pleural fluid assays, involving
      1,085 and 727 subjects, respectively. There was only one good-quality study, and
      five studies used nonstandard assay thresholds. The pooled sensitivity and
      specificity for the blood assays were 0.77 (95% CI, 0.71 to 0.83) and 0.71 (95%
      CI, 0.65 to 0.76), respectively. The pooled sensitivity and specificity for the
      pleural fluid assays were 0.72 (95% CI, 0.55 to 0.84) and 0.78 (95% CI, 0.65 to
      0.87), respectively. There was considerable heterogeneity; however, multivariate
      meta-regression did not identify any covariate with significant influence. There
      was no publication bias for blood assays. We conclude that commercial IGRAs,
      performed either on whole-blood or pleural fluid samples, have poor diagnostic
      accuracy in patients suspected to have TPE. 

PMID- 25994164
TI  - Rectal Carriage of Extended-Spectrum-Beta-Lactamase-Producing Enterobacteriaceae
      in Hospitalized Patients: Selective Preenrichment Increases Yield of Screening.
AB  - This study evaluated the added value of selective preenrichment for the detection
      of rectal carriage of extended-spectrum-beta-lactamase-producing
      Enterobacteriaceae (ESBL-E). ESBL-E rectal carriage was identified in 4.8% of
      hospitalized patients, and 25.9% of ESBL-E rectal carriers were identified with
      selective preenrichment only. 

PMID- 25994165
TI  - Identification of Gram-Negative Bacteria and Genetic Resistance Determinants from
      Positive Blood Culture Broths by Use of the Verigene Gram-Negative Blood Culture
      Multiplex Microarray-Based Molecular Assay.
AB  - Bloodstream infection is a serious condition associated with significant
      morbidity and mortality. The outcome of these infections can be positively
      affected by the early implementation of effective antibiotic therapy based on the
      identification of the infecting organism and genetic markers associated with
      antibiotic resistance. In this study, we evaluated the microarray-based Verigene
      Gram-negative blood culture (BC-GN) assay in the identification of 8 genus or
      species targets and 6 genetic resistance determinants in positive blood culture
      broths. A total of 1,847 blood cultures containing Gram-negative organisms were
      tested using the BC-GN assay. This comprised 729 prospective fresh, 781
      prospective or retrospective frozen, and 337 simulated cultures representing 7
      types of aerobic culture media. The results were compared to those with standard
      bacterial culture and biochemical identification with nucleic acid sequence
      confirmation of the resistance determinants. Among monomicrobial cultures, the
      positive percent agreement (PPA) of the BC-GN assay with the reference method was
      as follows; Escherichia coli, 100%; Klebsiella pneumoniae, 92.9%; Klebsiella
      oxytoca, 95.5%; Enterobacter spp., 99.3%; Pseudomonas aeruginosa, 98.9%; Proteus
      spp., 100%; Acinetobacter spp., 98.4%; and Citrobacter spp., 100%. All organism
      identification targets demonstrated >99.5% negative percent agreement (NPA) with
      the reference method. Of note, 25/26 cultures containing K. pneumoniae that were
      reported as not detected by the BC-GN assay were subsequently identified as
      Klebsiella variicola. The PPA for identification of resistance determinants was
      as follows; blaCTX-M, 98.9%; blaKPC, 100%; blaNDM, 96.2%; blaOXA, 94.3%; blaVIM,
      100%; and blaIMP, 100%. All resistance determinant targets demonstrated >99.9%
      NPA. Among polymicrobial specimens, the BC-GN assay correctly identified at least
      one organism in 95.4% of the broths and correctly identified all organisms
      present in 54.5% of the broths. The sample-to-result processing and automated
      reading of the detection microarray results enables results within 2 h of culture
      positivity. 

PMID- 25994166
TI  - Multitarget PCR Assay for Direct Detection of Penicillinase-Producing Neisseria
      gonorrhoeae for Enhanced Surveillance of Gonococcal Antimicrobial Resistance.
AB  - A multitarget PCR was developed for the direct detection of penicillinase
      producing Neisseria gonorrhoeae (PPNG). The assay was validated by testing 342
      PPNG isolates and 415 clinical samples. The method is suitable for routine
      detection of PPNG strains. Its multitarget approach reduces the potential for
      false-negative results caused by sequence variations. 

PMID- 25994167
TI  - Cost Savings Realized by Implementation of Routine Microbiological Identification
      by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.
AB  - Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass
      spectrometry (MS) is an emerging technology for rapid identification of bacterial
      and fungal isolates. In comparison to conventional methods, this technology is
      much less labor intensive and can provide accurate and reliable results in
      minutes from a single isolated colony. We compared the cost of performing the
      bioMerieux Vitek MALDI-TOF MS with conventional microbiological methods to
      determine the amount saved by the laboratory by converting to the new technology.
      Identification costs for 21,930 isolates collected between April 1, 2013, and
      March 31, 2014, were directly compared for MALDI-TOF MS and conventional
      methodologies. These isolates were composed of commonly isolated organisms,
      including commonly encountered aerobic and facultative bacteria and yeast but
      excluding anaerobes and filamentous fungi. Mycobacterium tuberculosis complex and
      rapidly growing mycobacteria were also evaluated for a 5-month period during the
      study. Reagent costs and a total cost analysis that included technologist time in
      addition to reagent expenses and maintenance service agreement costs were
      analyzed as part of this study. The use of MALDI-TOF MS equated to a net savings
      of $69,108.61, or 87.8%, in reagent costs annually compared to traditional
      methods. When total costs are calculated to include technologist time and
      maintenance costs, traditional identification would have cost $142,532.69, versus
      $68,886.51 with the MALDI-TOF MS method, resulting in a laboratory savings of
      $73,646.18, or 51.7%, annually by adopting the new technology. The initial cost
      of the instrument at our usage level would be offset in about 3 years. MALDI-TOF
      MS not only represents an innovative technology for the rapid and accurate
      identification of bacterial and fungal isolates, it also provides a significant
      cost savings for the laboratory. 

PMID- 25994168
TI  - Hepatitis C Virus Core Mutations Associated with False-Negative Serological
      Results for Genotype 3a Core Antigen.
AB  - Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core
      region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg
      positive/RNA-positive controls identified significant associations between the
      substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05).
      Polymorphisms at residues 48 and 49 in the core protein are present across all
      major epidemic and endemic GTs. These findings have implications for HCV
      diagnosis, particularly in low-income regions in which GT3a HCV is endemic. 

PMID- 25994169
TI  - Fatal West Nile Virus Encephalitis in a Heart Transplant Recipient.
AB  - The diagnosis of encephalitis is particularly challenging in immunocompromised
      patients. We report here a case of fatal West Nile virus encephalitis confounded
      by the presence of budding yeast in the cerebrospinal fluid (CSF) from a patient
      who had undergone heart transplantation for dilated cardiomyopathy 11 months
      prior to presentation of neurologic symptoms. 

PMID- 25994171
TI  - Molecular and ionic diffusion in aqueous - deep eutectic solvent mixtures:
      probing inter-molecular interactions using PFG NMR.
AB  - Pulsed field gradient (PFG) NMR has been used to probe self-diffusion of
      molecular and ionic species in aqueous mixtures of choline chloride (ChCl) based
      deep eutectic solvents (DESs), in order to elucidate the effect of water on
      motion and inter-molecular interactions between the different species in the
      mixtures, namely the Ch(+) cation and hydrogen bond donor (HBD). The results
      reveal an interesting and complex behaviour of such mixtures at a molecular
      level. In general, it is observed that the hydroxyl protons ((1)H) of Ch(+) and
      the hydrogen bond donor have diffusion coefficients significantly different from
      those measured for their parent molecules when water is added. This indicates a
      clear and significant change in inter-molecular interactions. In aqueous
      Ethaline, the hydroxyl species of Ch(+) and HBD show a stronger interaction with
      water as water is added to the system. In the case of Glyceline, water has little
      effect on both hydroxyl proton diffusion of Ch(+) and HBD. In Reline, it is
      likely that water allows the formation of small amounts of ammonium hydroxide.
      The most surprising observation is from the self-diffusion of water, which is
      considerably higher that expected from a homogeneous liquid. This leads to the
      conclusion that Reline and Glyceline form mixtures that are inhomogeneous at a
      microscopic level despite the hydrophilicity of the salt and HBD. This work shows
      that PFG NMR is a powerful tool to elucidate both molecular dynamics and inter
      molecular interactions in complex liquid mixtures, such as the aqueous DES
      mixtures. 

PMID- 25994170
TI  - A common assembly module in injectisome and flagellar type III secretion sorting
      platforms.
AB  - Translocating proteins across the double membrane of Gram-negative bacteria, type
      III secretion systems (T3SS) occur in two evolutionarily related forms:
      injectisomes, delivering virulence factors into host cells, and the flagellar
      system, secreting the polymeric filament used for motility. While both systems
      share related elements of a cytoplasmic sorting platform that facilitates the
      hierarchical secretion of protein substrates, its assembly and regulation remain
      unclear. Here we describe a module mediating the assembly of the sorting platform
      in both secretion systems, and elucidate the structural basis for segregation of
      homologous components among these divergent T3SS subtypes sharing a common
      cytoplasmic milieu. These results provide a foundation for the subtype-specific
      assembly of T3SS sorting platforms and will support further mechanistic analysis
      and anti-virulence drug design. 

PMID- 25994172
TI  - Down-regulation of miR-23b induces phenotypic switching of vascular smooth muscle
      cells in vitro and in vivo.
AB  - AIMS: Phenotypic switch of vascular smooth muscle cells (VSMCs) plays a key role
      in the pathogenesis of different vascular diseases, such as atherosclerosis and
      restenosis after coronary intervention. MicroRNAs have been identified as key
      regulators of VSMC biology. The miR-23b is highly expressed in VSMCs and it is
      involved in differentiation, proliferation, and migration of several non-vascular
      cell types. However, the role of miR-23b in vascular disease is currently
      unknown. Thus, the aim of the present study was to evaluate the role of miR-23b
      on VSMC phenotypic switch in vitro and after vascular injury in vivo. METHODS AND
      RESULTS: To determine the changes of miR-23b expression in the injured arterial
      wall, we used the standard rat carotid artery balloon injury model. In vivo
      studies demonstrated that miR-23b is down-regulated after vascular injury. Gain
      of-function studies showed that overexpression of miR-23b inhibited VSMC
      proliferation and migration, whereas the opposite effect was obtained with the in
      vitro inhibition of miR-23b. We further demonstrated that miR-23b can
      significantly promote the expression of VSMC marker genes such as smooth muscle
      alpha-actin (ACTA2) and smooth muscle myosin heavy chain (MYH11). Overexpression
      of miR-23b in balloon-injured arteries by Ad-miR-23b markedly decreased
      neointimal hyperplasia. Finally, miR-23b specifically suppresses urokinase-type
      plasminogen activator, SMAD family member 3, and transcription factor forkhead
      box O4 (FoxO4) expression in phenotypically modulated VSMCs. By luciferase
      reporter assay, we validated the transcription factor FoxO4 as a direct target of
      miR-23b in VSMCs. CONCLUSIONS: We identify miR-23b as a novel regulator of VSMC
      phenotypic switch in vitro and following vascular injury in vivo.

PMID- 25994173
TI  - Dual signals underlying diabetic lymphatic barrier dysregulation.

PMID- 25994174
TI  - Selectins: initiators of leucocyte adhesion and signalling at the vascular wall.
AB  - The selectins are transmembrane, Ca(2+)-dependent lectins that mediate leucocyte
      rolling on vascular surfaces, the first adhesive step during inflammation and
      immune surveillance. Leucocytes express L-selectin, activated platelets express P
      selectin, and activated endothelial cells express E- and P-selectin. Rolling
      involves force-regulated, rapidly reversible interactions of selectins with a
      limited number of glycosylated cell surface ligands. Rolling permits leucocytes
      to interact with immobilized chemokines that convert beta2 integrins to high
      affinity conformations, which mediate arrest, post-arrest adhesion strengthening,
      and transendothelial migration. However, rolling leucocytes also transduce
      signals through selectin ligands, the focus of this review. These signals include
      serial activation of kinases and recruitment of adaptors that convert integrins
      to intermediate-affinity conformations, which decrease rolling velocities. In
      vitro, selectin signalling enables myeloid cells to respond to suboptimal levels
      of chemokines and other agonists. This cooperative signalling triggers effector
      responses such as degranulation, superoxide production, chemokine synthesis, and
      release of procoagulant/proinflammatory microparticles. In vivo, selectin
      mediated adhesion and signalling likely contributes to atherosclerosis, arterial
      and deep vein thrombosis, ischaemia-reperfusion injury, and other cardiovascular
      diseases. 

PMID- 25994175
TI  - Efficacy of steroid addition to multimodal cocktail periarticular injection in
      total knee arthroplasty: a meta-analysis.
AB  - BACKGROUND: Total knee arthroplasty (TKA) has been reported to be the most
      successful treatment for patients with advanced osteoarthritis, however, early
      postoperative pain has become an unresolved issue. The aim of this Meta-analysis
      is to evaluate the efficacy and safety of steroid addition to multimodal cocktail
      periarticular injection (MCPI) in patients undergoing TKA. METHOD: Clinical
      randomized controlled trials concerning the efficacy and safety of MCPI
      containing steroids in TKA published up to December 2014 were retrieved from
      PubMed, Cochrane library, EMbase databases. The methodological quality of the
      included studies was assessed by the 12-item scale. Data analysis was performed
      using StataSE12.0. RESULTS: Six randomized controlled trials involving a total of
      567 patients were assessed; the steroid group included 305 patients, and the
      control group included 262 patients. The meta-analysis showed that MCPI with
      steroids in TKA significantly reduced postoperative pain; duration of time
      required to perform straight-leg raising and length of hospital stay was (P <
      0.05). Neither the early postoperative nor the long-term range of motion of knee
      showed any statistical difference between the non-steroid and steroid group (P
      >0.05). For safety, steroids did not increase the incidence of postoperative
      infection and wound oozing (P >0.05); no tendon rupture was reported up to now.
      In addition, steroids did not decrease the postoperative drainage through the
      reduction of prostaglandins (P >0.05). CONCLUSION: For patients undergoing TKA,
      the addition of steroids to MCPI improved the analgesic effect and was proved to
      be highly safe. The duration of time required to perform straight-leg raising and
      length of hospital stay was significantly reduced. However, MCPI with steroids
      neither increased the early postoperative range of motion (ROM) or the long-term
      ROM of knee, nor did it reduce the postoperative drainage. However, the best
      results are acquired in patients without any altered immunological status.

PMID- 25994176
TI  - Visual Inspection for Caries Detection: A Systematic Review and Meta-analysis.
AB  - We aimed to perform a systematic review including a meta-analysis to evaluate the
      overall accuracy of visual methods for detecting carious lesions and to identify
      possible sources of heterogeneity among the studies included. Two reviewers
      searched PubMed, Embase, Scopus, and other sources through July 2014 to identify
      published and nonpublished studies in English. Studies of visual inspection were
      included that 1) assessed accuracy of the method in detecting caries lesions; 2)
      were performed on occlusal, proximal, or free smooth surfaces in primary or
      permanent teeth; 3) had a reference standard; and 4) reported sufficient data
      about sample size and accuracy of methods. The data were used to calculate the
      pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver
      operating characteristics curve. Heterogeneity of the studies was also assessed.
      A total of 102 manuscripts (from 5,808 articles initially identified) and 1
      abstract (from 168) met the inclusion criteria. In general, the analysis
      demonstrated that the visual method had good accuracy for detecting caries
      lesions. Although laboratory and clinical studies have presented similar
      accuracy, clinically obtained specificity was higher. We also observed moderate
      to high heterogeneity and evidence of publication bias in most papers. Moreover,
      studies employing widely recognized visual scoring systems presented
      significantly better accuracy as compared to studies that used their own
      criteria. In conclusion, visual caries detection method has good overall
      performance. Furthermore, although the identified studies had high heterogeneity
      and risk of bias, the use of detailed and validated indices seems to improve the
      accuracy of the method. 

PMID- 25994177
TI  - Orthodontic Force Facilitates Cortical Responses to Periodontal Stimulation.
AB  - Somatosensory information derived from the periodontal ligaments plays a critical
      role in identifying the strength and direction of occlusal force. The orthodontic
      force needed to move a tooth often causes uncomfortable sensations, including
      nociception around the tooth, and disturbs somatosensory information processing.
      However, it has mostly remained unknown whether orthodontic treatment modulates
      higher brain functions, especially cerebrocortical activity. To address this
      issue, we first elucidated the cortical region involved in sensory processing
      from the periodontal ligaments and then examined how experimental tooth movement
      (ETM) changes neural activity in these cortical regions. We performed in vivo
      optical imaging to identify the cortical responses evoked by electrical
      stimulation of the maxillary and mandibular incisor and the first molar
      periodontal ligaments in the rat. In naive rats, electrical stimulation of the
      mandibular periodontal ligaments initially evoked neural excitation in the
      rostroventral part of the primary somatosensory cortex (S1), the ventrocaudal
      part of the secondary somatosensory cortex (S2), and the insular oral region
      (IOR), whereas maxillary periodontal ligaments elicited excitation only in S2/IOR
      rostrodorsally adjacent to the mandibular periodontal ligament-responding region.
      In contrast, maximum responses to mandibular and maxillary periodontal
      stimulation were observed in S1 and S2/IOR, and the 2 responses nearly
      overlapped. One day after ETM (maxillary molar movement by Waldo's method), the
      maximum response to stimulation of the maxillary molar periodontal ligament
      induced larger and broader excitation in S2/IOR, although the initial responses
      were not affected. Taken together with the histologic findings of IL-1beta
      expression and macrophage infiltration in the periodontal ligament of the ETM
      models, inflammation induced by ETM may play a role in the facilitation of S2/IOR
      activity. From the clinical viewpoints, the larger amplitude of cortical
      excitation may induce higher sensitivity to pain responding to nonnoxious
      stimuli, and enlargement of the responding area may reflect radiating pain. 

PMID- 25994178
TI  - Income Inequality and Use of Dental Services in 66 Countries.
AB  - This study explored the association between income inequality and use of dental
      services and the role that investment in health care plays in explaining that
      association. We pooled individual-level data from 223,299 adults, 18 years or
      older, in 66 countries, who participated in the World Health Organization (WHO)
      World Health Surveys with country-level data from different international
      sources. Income inequality was measured at the national level using the Gini
      coefficient, and use of dental services was defined as having received treatment
      to address problems with mouth and/or teeth in the past year. The association
      between the Gini coefficient and use of dental services was examined in
      multilevel models controlling for a standard set of individual- and country-level
      confounders. The individual and joint contributions of 4 indicators of investment
      in health care were evaluated in sequential modeling. The Gini coefficient and
      use of dental services were inversely associated after adjustment for
      confounders. Every 10% increase in the Gini coefficient corresponded with a 15%
      lower odds of using dental services (odds ratio: 0.85; 95% confidence interval:
      0.70-0.99). The association between the Gini coefficient and use of dental
      services was attenuated and became nonsignificant after individual adjustment for
      total health expenditure, public expenditure on health, health system
      responsiveness, or type of dental health system. The 4 indicators together
      explained 80% of the association between the Gini coefficient and use of dental
      services. This study suggests that more equal countries have greater use of
      dental services. It also supports the mediating role of investment in health care
      in explaining that association. 

PMID- 25994179
TI  - Effect of etanercept therapy on psoriasis symptoms in patients from Latin
      America, Central Europe, and Asia: a subset analysis of the PRISTINE trial.
AB  - BACKGROUND: Psoriasis prevalence and characteristics in Asia, Central Europe, and
      Latin America have not been thoroughly investigated and there are no large trials
      for biologic treatments for patients from these regions. The goal of this
      analysis was to report clinical response to anti-tumor necrosis factor-alpha
      treatment in these patients. METHODS: Patients from Argentina, Czech Republic,
      Hungary, Mexico, Taiwan, and Thailand (N=171) were included in this subset
      analysis of the PRISTINE trial. Patients with stable moderate-to-severe plaque
      psoriasis were blinded and randomized to receive etanercept 50 mg once weekly
      (QW) or biweekly (BIW) for 12 weeks, followed by 12 weeks of open-label QW
      treatment with etanercept 50 mg through week 24 (QW/QW vs. BIW/QW). Concomitant
      methotrexate (<=20 mg/week) and mild topical corticosteroids or other agents were
      permitted at the physician's discretion, in accordance with therapeutic practice.
      RESULTS: As early as week 8, 26.7 % in the etanercept QW group and 44.0 % in the
      BIW group achieved Psoriasis Area and Severity Index (PASI) 75. At weeks 12 and
      24, respectively, PASI 75 increased to 39.5 % and 62.8 % in the QW/QW group and
      66.7 % and 83.3 % in the BIW/QW group. PASI 75 was significantly different
      between treatment groups from week 8 through the end of study (p<0.05). The
      Kaplan-Meier estimate of the proportions achieving PASI 75 in QW/QW and BIW/QW
      groups, respectively, was 27.4 % and 45.8 % through week 8; 41.9 % and 68.7 %
      through week 12; and 72.5 % and 95.2 % through week 24. CONCLUSIONS: Treatment
      with etanercept 50 mg provided rapid relief of psoriasis symptoms in patients
      from Asia, Central Europe, and Latin America. A more rapid response was observed
      in patients who received BIW treatment for the first 12 weeks which was sustained
      after reducing to QW dosing for the subsequent 12 weeks. Response rates were
      similar to those observed in the overall PRISTINE population. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier NCT00663052 .

PMID- 25994180
TI  - The preclinical pharmacology of the high affinity anti-IL-6R Nanobody(r) ALX-0061
      supports its clinical development in rheumatoid arthritis.
AB  - INTRODUCTION: The pleiotropic cytokine interleukin-6 (IL-6) plays an important
      role in the pathogenesis of different diseases, including rheumatoid arthritis
      (RA). ALX-0061 is a bispecific Nanobody(r) with a high affinity and potency for
      IL-6 receptor (IL-6R), combined with an extended half-life by targeting human
      serum albumin. We describe here the relevant aspects of its in vitro and in vivo
      pharmacology. METHODS: ALX-0061 is composed of an affinity-matured IL-6R
      targeting domain fused to an albumin-binding domain representing a minimized two
      domain structure. A panel of different in vitro assays was used to characterize
      the biological activities of ALX-0061. The pharmacological properties of ALX-0061
      were examined in cynomolgus monkeys, using plasma levels of total soluble (s)IL
      6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6
      induced acute phase response model in the same species, and in a collagen-induced
      arthritis (CIA) model in rhesus monkeys, using tocilizumab as positive control.
      RESULTS: ALX-0061 was designed to confer the desired pharmacological properties.
      A 200-fold increase of target affinity was obtained through affinity maturation
      of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a
      concentration-dependent and complete neutralization of sIL-6R in vitro. In
      cynomolgus monkeys, ALX-0061 showed a dose-dependent and complete inhibition of
      hIL-6-induced inflammatory parameters, including plasma levels of C-reactive
      protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days
      was observed after a single intravenous administration of 10 mg/kg ALX-0061 in
      cynomolgus monkeys, similar to the estimated expected half-life of serum albumin.
      ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a
      non-human primate CIA model. Clinical effect was confirmed in animals with active
      drug exposure throughout the study duration. CONCLUSIONS: ALX-0061 represents a
      minimized bispecific biotherapeutic of 26 kDa, nearly six times smaller than
      monoclonal antibodies. High in vitro affinity and potency was demonstrated.
      Albumin binding as a half-life extension technology resulted in describable and
      expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in
      vivo effect in non-human primates, demonstrated via biomarker deregulation as
      well as clinical effect. Presented results on preclinical pharmacological
      properties of ALX-0061 are supportive of clinical development in RA.

PMID- 25994181
TI  - Comparative analysis of plant carbohydrate active enZymes and their role in
      xylogenesis.
AB  - BACKGROUND: Carbohydrate metabolism is a key feature of vascular plant
      architecture, and is of particular importance in large woody species, where
      lignocellulosic biomass is responsible for bearing the bulk of the stem and
      crown. Since Carbohydrate Active enZymes (CAZymes) in plants are responsible for
      the synthesis, modification and degradation of carbohydrate biopolymers, the
      differences in gene copy number and regulation between woody and herbaceous
      species have been highlighted previously. There are still many unanswered
      questions about the role of CAZymes in land plant evolution and the formation of
      wood, a strong carbohydrate sink. RESULTS: Here, twenty-two publically available
      plant genomes were used to characterize the frequency, diversity and complexity
      of CAZymes in plants. We find that a conserved suite of CAZymes is a feature of
      land plant evolution, with similar diversity and complexity regardless of growth
      habit and form. In addition, we compared the diversity and levels of CAZyme gene
      expression during wood formation in trees using mRNA-seq data from two distantly
      related angiosperm tree species Eucalyptus grandis and Populus trichocarpa,
      highlighting the major CAZyme classes involved in xylogenesis and lignocellulosic
      biomass production. CONCLUSIONS: CAZyme domain ratio across embryophytes is
      maintained, and the diversity of CAZyme domains is similar in all land plants,
      regardless of woody habit. The stoichiometric conservation of gene expression in
      woody and non-woody tissues of Eucalyptus and Populus are indicative of gene
      balance preservation.

PMID- 25994182
TI  - Effect of Ganoderma lucidum spores intervention on glucose and lipid metabolism
      gene expression profiles in type 2 diabetic rats.
AB  - BACKGROUND: The fruiting body of Ganoderma lucidum has been used as a traditional
      herbal medicine for many years. However, to the date, there is no detailed study
      for describing the effect of G. lucidum spores on oxidative stress, blood glucose
      level and lipid compositions in animal models of type 2 diabetic rats, in
      particular the effect on the gene expression profiles associated with glucose and
      lipid metabolisms. METHODS: G. lucidum spores powder (GLSP) with a shell-broken
      rate >99.9 % was used. Adult male Sprague-Dawley rats were randomly divided into
      three groups (n = 8/group). Group 1: Normal control, normal rats with ordinary
      feed; Group 2: Model control, diabetic rats with ordinary feed without
      intervention; Group 3: GLSP, diabetic rats with ordinary feed, an intervention
      group utilizing GLSP of 1 g per day by oral gavages for 4 consecutive weeks. Type
      2 diabetic rats were obtained by streptozocin (STZ) injection. The changes in the
      levels of glucose, triglycerides, total cholesterol and HDL-cholesterol in blood
      samples were analyzed after GLSP intervention. Meanwhile, gene expressions
      associated with the possible molecular mechanism of GLSP regulation were also
      investigated using a quantitative RT-PCR. RESULTS: The reduction of blood glucose
      level occurred within the first 2 weeks of GLSP intervention and the lipid
      synthesis in the diabetic rats of GLSP group was significantly decreased at 4
      weeks compared to the model control group. Furthermore, it was also found that
      GLSP intervention greatly attenuated the level of oxidative stress in the
      diabetic rats. Quantitative RT-PCR analysis showed up-regulation of lipid
      metabolism related genes (Acox1, ACC, Insig-1 and Insig-2) and glycogen synthesis
      related genes (GS2 and GYG1) in GLSP group compared to model control group.
      Additionally, there were no significant changes in the expression of other genes,
      such as SREBP-1, Acly, Fas, Fads1, Gpam, Dgat1, PEPCK and G6PC1. CONCLUSION: This
      study might indicate that GLSP consumption could provide a beneficial effect in
      terms of lowering the blood glucose levels by promoting glycogen synthesis and
      inhibiting gluconeogenesis. Meanwhile, GLSP treatment was also associated with
      the improvement of blood lipid compositions through the regulation of cholesterol
      homeostasis in the type 2 diabetic rats.

PMID- 25994183
TI  - Ancient origin of the biosynthesis of lignin precursors.
AB  - BACKGROUND: Lignin plays an important role in plant structural support and water
      transport, and is considered one of the hallmarks of land plants. The recent
      discovery of lignin or its precursors in various algae has raised questions on
      the evolution of its biosynthetic pathway, which could be much more ancient than
      previously thought. To determine the taxonomic distribution of the lignin
      biosynthesis genes, we screened all publicly available genomes of algae and their
      closest non-photosynthetic relatives, as well as representative land plants. We
      also performed phylogenetic analysis of these genes to decipher the evolution and
      origin(s) of lignin biosynthesis. RESULTS: Enzymes involved in making p-coumaryl
      alcohol, the simplest lignin monomer, are found in a variety of photosynthetic
      eukaryotes, including diatoms, dinoflagellates, haptophytes, cryptophytes as well
      as green and red algae. Phylogenetic analysis of these enzymes suggests that they
      are ancient and spread to some secondarily photosynthetic lineages when they
      acquired red and/or green algal endosymbionts. In some cases, one or more of
      these enzymes was likely acquired through lateral gene transfer (LGT) from
      bacteria. CONCLUSIONS: Genes associated with p-coumaryl alcohol biosynthesis are
      likely to have evolved long before the transition of photosynthetic eukaryotes to
      land. The original function of this lignin precursor is therefore unlikely to
      have been related to water transport. We suggest that it participates in the
      biological defense of some unicellular and multicellular algae.

PMID- 25994185
TI  - Coloring Rate of Phenolphthalein by Reaction with Alkaline Solution Observed by
      Liquid-Droplet Collision.
AB  - Many important chemical reactions are induced by mixing two solutions. This paper
      presents a new way to measure rates of rapid chemical reactions induced by mixing
      two reactant solutions using a liquid-droplet collision. The coloring reaction of
      phenolphthalein (H2PP) by a reaction with NaOH is investigated kinetically.
      Liquid droplets of H2PP/ethanol and NaOH/H2O solutions are made to collide, which
      induces a reaction that transforms H2PP into a deprotonated form (PP(2-)). The
      concentration of PP(2-) is evaluated from the RGB values of pixels in the colored
      droplet images, and is measured as a function of the elapsed time from the
      collision. The obtained rate constant is (2.2 +/- 0.7) * 10(3) M(-1) s(-1), which
      is the rate constant for the rate-determining step of the coloring reaction of
      H2PP. This method was shown to be applicable to determine rate constants of rapid
      chemical reactions between two solutions. 

PMID- 25994184
TI  - Serum leptin levels are independently related to the incidence of ischemic heart
      disease in a prospective study of patients with type 2 diabetes.
AB  - BACKGROUND: New and clinically useful markers of cardiovascular risk are of
      essence in type 2 diabetes since ischemic heart disease is a major cause of death
      in these patients. METHODS: We analyzed baseline data from 476 men and 244 women
      who participated in "Cardiovascular Risk factors in Patients with Diabetes -a
      Prospective study in Primary care" study. All participants had type 2 diabetes
      and were 55-66 years old at recruitment during year 2005 to 2008. Except for
      established traditional risk markers for vascular disease, we also estimated
      vascular complications non-invasively by performance of carotid-femoral pulse
      wave velocity (PWV, with applanation-tonometry) and intima-media thickness of
      carotid arteries (IMT, with B-mode ultrasound). Patients were followed for
      incidence of ischemic heart disease mortality and morbidity until end of the year
      2012, using the national Swedish Cause of Death and Hospitalization Registries.
      RESULTS: During the follow-up period of a median of 6 years 47 men and 10 women
      died or were hospitalized for ischemic heart disease including myocardial
      infarction. Leptin levels were positively related to the hazard ratio (HR) in men
      (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to
      89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI,
      systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9
      CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to
      high leptin levels was also statistically significant when carotid-femoral PWV
      and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41).
      CONCLUSIONS: Our data support the use of serum leptin in type 2 diabetes to add
      independent prognostic information in terms of ischemic heart disease when
      compared with traditional cardiovascular risk factors. In the men of the cohort
      this prognostic information was in addition also to data on IMT and PWV, two non
      invasive measurements of the extent of vascular disease. The power to detect a
      similar relationship in women was less strong due to lower incidence of
      cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01049737.

PMID- 25994186
TI  - Health-related quality of life is associated with stroke deficits in older
      adults.
AB  - BACKGROUND/OBJECTIVES: although the functional impairments of stroke survivors
      are associated with poor health-related quality of life (HRQoL), few studies have
      demonstrated the impact of individual stroke deficits on the quality of life of
      survivors. In this study, we investigated the association between HRQoL and
      stroke-related deficits, especially with respect to the number and types of
      deficits, in older adults. METHODS: the data were obtained from the 2008 and 2009
      Korean Community Health Survey. The EuroQoL 5 Dimension (EQ-5D) questionnaire
      used as the HRQoL index, and stroke-related information included the number of
      stroke deficits and five types of deficits. RESULTS: of the 122,095 participants,
      6,698 (5.5%) subjects had a history of stroke, of whom 2,222 patients (33.2%)
      reported one or more stroke-related deficits. After adjustments for potential
      variables, the EQ-5D scores of the stroke survivors with persisting deficits were
      significantly reduced as the number of stroke deficits increased (beta = -0.080, 
      0.147, -0.229, -0.252 and -0.293 for one, two, three, four and five deficits,
      respectively). The type of stroke deficits was associated with the level of
      HRQoL. Specifically, the adjusted EQ-5D score of patients who suffered from
      hemiplegia (beta = -0.143; P value < .00001) was worse than that of patients with
      any stroke deficits. The most frequent problems were related to mobility and
      pain/discomfort, regardless of the number or type of stroke deficits. CONCLUSION:
      we found that impaired HRQoL was significantly associated with the number and
      type of stroke deficits in older adults with a history of stroke.

PMID- 25994187
TI  - Effect of apolipoprotein C3 genetic polymorphisms on serum lipid levels and the
      risk of intracerebral hemorrhage.
AB  - BACKGROUND: Serum lipid levels are associated with the risk of intracerebral
      hemorrhage (ICH). Genetic variants in the apolipoprotein C3 (APOC3) gene were
      associated with plasma triglyceride (TG) and very-low-density lipoprotein (VLDL)
      levels. The aim of this study was to evaluate the effect of two genetic variants
      (1100 C/T and 3238 C/G) of APOC3 on serum lipid levels and risk of ICH. METHODS:
      A prospective hospital-based case-control design and logistic regression analysis
      were utilized. We enrolled 150 ICH patients and 150 age- and gender-matched
      controls. The APOC3 gene polymorphisms were determined by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: ICH
      patients had a significantly higher frequency of APOC3 3238 GG genotype [odds
      ratio (OR)=.97, 95% confidence interval (CI)=1.20, 7.38; P=0.02] and APOC3 3238 G
      allele (OR=.53, 95% CI=1.03, 2.27; P=0.04) than controls. The APOC3 3238 G allele
      was significantly associated with increasing plasma TG levels and VLDL levels
      both in ICH cases (P=0.01) and controls (P=0.02). No association was found
      between APOC3 1100 C/T polymorphisms and ICH. CONCLUSION: To the best of our
      knowledge, this is the first report in the literature that the APOC3 3238 GG
      genotype and G allele might contribute to an increased risk of ICH as a result of
      its effect on serum lipid levels.

PMID- 25994188
TI  - Clinical assessment of Shenfu injection loading in the treatment of patients with
      exacerbation of chronic heart failure due to coronary heart disease: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Acute exacerbation is a common cause of hospitalization in patients
      with chronic heart failure, and coronary heart disease is the most common cause.
      Shenfu injection, a Traditional Chinese Medicine injection, widely used in the
      adjuvant treatment of patients with acute exacerbation of chronic heart failure,
      shows some treatment effect in improving the symptoms and the quality of life,
      but it lacks the rigorous clinical evaluation of research reports. This paper
      describes the protocol for the clinical assessment of Shenfu injection loading in
      the treatment of patients with acute exacerbation of chronic heart failure.
      METHODS: This protocol adopts the design of a prospective, randomized,
      multicenter, blind imitation, placebo-controlled trial to assess the efficacy and
      safety of Shenfu injection loading in the treatment of patients with acute
      exacerbation of chronic heart failure due to coronary heart disease. The research
      will be carried out in 12 hospitals in China and is expected to enroll 160
      inpatients with acute exacerbation of chronic heart failure due to coronary heart
      disease (yang and qi deficiency syndrome). On the basis of the conventional
      therapy of western medicine, patients will be randomized to either the treatment
      group (100 ml 5% glucose injection + 50 ml Shenfu injection) or the control group
      (150 ml 5% glucose injection) for 7 +/- 1 days and follow-up for 28 +/- 3 days.
      The primary outcomes are New York Heart Association cardiac function
      classification and Traditional Chinese Medicine syndromes. The secondary outcomes
      are left ventricular ejection fraction, brain natriuretic peptide level, Lee's
      heart failure score, 6-minute walking distance, and the incidence and readmission
      rate of cardiovascular events (including the emergency rate due to acute
      exacerbation of chronic heart failure). DISCUSSION: This trial will assess the
      effect of loading Shenfu injection in the treatment of patients with acute
      exacerbation of chronic heart failure caused by coronary heart disease (yang-qi
      deficiency syndrome) on the symptoms and signs of heart failure, exercise
      tolerance, and other aspects, and observe its influence on the short-term
      prognosis with follow-up. The results of the study will provide clinical research
      evidence for application of Shenfu injection in the treatment. TRIAL
      REGISTRATION: This trial was registered on 26 December 2012 at the Chinese
      Clinical Trials Register (Identifier: ChiCTR-TRC-12002857 ).

PMID- 25994189
TI  - The precision of textural analysis in (18)F-FDG-PET scans of oesophageal cancer.
AB  - OBJECTIVES: Measuring tumour heterogeneity by textural analysis in (18)F
      fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) provides
      predictive and prognostic information but technical aspects of image processing
      can influence parameter measurements. We therefore tested effects of image
      smoothing, segmentation and quantisation on the precision of heterogeneity
      measurements. METHODS: Sixty-four (18)F-FDG PET/CT images of oesophageal cancer
      were processed using different Gaussian smoothing levels (2.0, 2.5, 3.0, 3.5, 4.0
      mm), maximum standardised uptake value (SUVmax) segmentation thresholds (45%,
      50%, 55%, 60%) and quantisation (8, 16, 32, 64, 128 bin widths). Heterogeneity
      parameters included grey-level co-occurrence matrix (GLCM), grey-level run length
      matrix (GLRL), neighbourhood grey-tone difference matrix (NGTDM), grey-level size
      zone matrix (GLSZM) and fractal analysis methods. The concordance correlation
      coefficient (CCC) for the three processing variables was calculated for each
      heterogeneity parameter. RESULTS: Most parameters showed poor agreement between
      different bin widths (CCC median 0.08, range 0.004-0.99). Segmentation and
      smoothing showed smaller effects on precision (segmentation: CCC median 0.82,
      range 0.33-0.97; smoothing: CCC median 0.99, range 0.58-0.99). CONCLUSIONS:
      Smoothing and segmentation have only a small effect on the precision of
      heterogeneity measurements in (18)F-FDG PET data. However, quantisation often has
      larger effects, highlighting a need for further evaluation and standardisation of
      parameters for multicentre studies. KEY POINTS: * Heterogeneity measurement
      precision in (18) F-FDG PET is influenced by image processing methods. *
      Quantisation shows large effects on precision of heterogeneity parameters in (18)
      F-FDG PET/CT. * Smoothing and segmentation show comparatively smaller effects on
      precision of heterogeneity parameters.

PMID- 25994190
TI  - Clinical Feasibility of 3D Automated Coronary Atherosclerotic Plaque
      Quantification Algorithm on Coronary Computed Tomography Angiography: Comparison
      with Intravascular Ultrasound.
AB  - OBJECTIVE: To evaluate the diagnostic performance of automated coronary
      atherosclerotic plaque quantification (QCT) by different users (expert/non
      expert/automatic). METHODS: One hundred fifty coronary artery segments from 142
      patients who underwent coronary computed tomography angiography (CCTA) and
      intravascular ultrasound (IVUS) were analyzed. Minimal lumen area (MLA), maximal
      lumen area stenosis percentage (%AS), mean plaque burden percentage (%PB), and
      plaque volume were measured semi-automatically by expert, non-expert, and fully
      automatic QCT analyses, and then compared to IVUS. RESULTS: Between IVUS and
      expert QCT analysis, the correlation coefficients (r) for the MLA, %AS, %PB, and
      plaque volume were excellent: 0.89 (p < 0.001), 0.84 (p < 0.001), 0.91 (p <
      0.001), and 0.94 (p < 0.001), respectively. There were no significant differences
      in the mean parameters (all p values >0.05) except %AS (p = 0.01). The automatic
      QCT analysis showed comparable performance to non-expert QCT analysis, showing
      correlation coefficients (r) of the MLA (0.80 vs. 0.82), %AS (0.82 vs. 0.80), %PB
      (0.84 vs. 0.73), and plaque volume (0.84 vs. 0.79) when they were compared to
      IVUS, respectively. CONCLUSION: Fully automatic QCT analysis showed clinical
      utility compared with IVUS, as well as a compelling performance when compared
      with semiautomatic analyses. KEY POINTS: * Coronary CTA enables the assessment of
      coronary atherosclerotic plaque. * High-risk plaque characteristics and overall
      plaque burden can predict future cardiac events. * Coronary atherosclerotic
      plaque quantification is currently unfeasible in practice. * Quantitative
      computed tomography coronary plaque analysis software (QCT) enables feasible
      plaque quantification. * Fully automatic QCT analysis shows excellent
      performance.

PMID- 25994191
TI  - Cost-utility analysis of nonalcoholic steatohepatitis screening.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common liver
      disease in Western countries. No studies have examined the cost-effectiveness of
      screening its advanced form, nonalcoholic steatohepatitis (NASH). METHODS: We
      performed a cost-utility analysis of annual noninvasive screening strategies
      using third-party payer perspective in a general population in comparison to
      screening a high-risk obese or diabetic population. Screening algorithms involved
      well-studied techniques, including NAFLD fibrosis score, transient elastography
      (TE), and acoustic radiation force impulse (ARFI) imaging for detecting advanced
      fibrosis (>= F3); and plasma cytokeratin (CK)-18 for NASH detection. Liver biopsy
      and magnetic resonance elastography (MRE) were compared as confirmation methods.
      Canadian dollar (CAD or C$) costs were adjusted for inflation and discounted at
      5%. Incremental cost-effectiveness ratio (ICER) of <=C$ 50,000 was considered
      cost-effective. RESULTS: Compared with no screening, screening with NAFLD
      fibrosis score/TE/CK-18 algorithm with MRE as confirmation for advanced fibrosis
      had an ICER of C$ 26,143 per quality-adjusted life year (QALY) gained. Screening
      in high-risk obese or diabetic populations was more cost-effective, with an ICER
      of C$ 9,051 and C$ 7,991 per quality-adjusted life-year (QALY) gained,
      respectively. Liver biopsy confirmation was not found to be cost-effective.
      CONCLUSIONS: Our model suggests that annual NASH screening in high-risk obese or
      diabetic populations can be cost-effective. KEY POINTS: * This cost-utility
      analysis suggests that screening for nonalcoholic steatohepatitis may be cost
      effective. * In particular, screening of high-risk obese or diabetic populations
      is more cost-effective. * Magnetic resonance elastography was more cost-effective
      to confirm disease compared to biopsy. * More studies are needed to determine
      quality of life in nonalcoholic steatohepatitis. * More management strategies for
      nonalcoholic steatohepatitis are also needed.

PMID- 25994192
TI  - Prevalence of cartilaginous tumours as an incidental finding on MRI of the knee.
AB  - OBJECTIVES: The purpose was to determine prevalence of enchondromas and atypical
      cartilaginous tumour/chondrosarcoma grade 1 (ACT/CS1) of the knee on MRI in a
      large cohort study, namely the Netherlands Epidemiology of Obesity (NEO) study.
      METHODS: Participants aged 45 to 65 years were prospectively included,
      oversampling overweight and obese persons. Within a subgroup of participants, MRI
      of the right knee was performed and screened for incidental cartilaginous
      tumours, as defined by their characteristic location and appearance. RESULTS:
      Forty-nine cartilaginous tumours were observed in 44 out of 1285 participants
      (estimated population prevalence 2.8 %, 95 % CI 2.0-4.0 %). Mean largest tumour
      diameter was 12 mm (range 2-31 mm). Eight participants with a tumour larger than
      20 mm or a tumour with aggressive features were referred to rule out low-grade
      chondrosarcoma. One was lost to follow-up, three had histologically proven
      ACT/CS1 and four had dynamic contrast MRI findings consistent with benign
      enchondroma. CONCLUSIONS: Incidental cartilaginous tumours were relatively common
      on knee MRI and may be regarded as a normal concurrent finding. However, more
      tumours than expected were ACT/CS1. Because further examination was performed
      only when suspicion of chondrosarcoma was high, the actual prevalence might be
      even higher. KEY POINTS: * Incidental cartilaginous tumours are relatively common
      on knee MRI. * Most incidental cartilaginous tumours are small and lack
      suspicious features. * Small cartilaginous tumours without suspicious findings
      may be a normal concurrent finding. * Large tumours and/or those with suspicious
      findings should be further investigated. * Atypical cartilaginous
      tumour/chondrosarcoma grade 1 was found more often than expected.

PMID- 25994194
TI  - Sublingual Nitroglycerin Administration in Coronary Computed Tomography
      Angiography: a Systematic Review.
AB  - OBJECTIVE: To systematically investigate the literature for the influence of
      sublingual nitroglycerin administration on coronary diameter, the number of
      evaluable segments, image quality, heart rate and blood pressure, and diagnostic
      accuracy of coronary computed tomography (CT) angiography. METHODS: A systematic
      search was performed in PubMed, EMBASE and Web of Science. The studies were
      evaluated for the effect of sublingual nitroglycerin on coronary artery diameter,
      evaluable segments, objective and subjective image quality, systemic
      physiological effects and diagnostic accuracy. Due to the heterogeneous reporting
      of outcome measures, a narrative synthesis was applied. RESULTS: Of the 217
      studies identified, nine met the inclusion criteria: seven reported on the effect
      of nitroglycerin on coronary artery diameter, six on evaluable segments, four on
      image quality, five on systemic physiological effects and two on diagnostic
      accuracy. Sublingual nitroglycerin administration resulted in an improved
      evaluation of more coronary segments, in particular, in smaller coronary
      branches, better image quality and improved diagnostic accuracy. Side effects
      were mild and were alleviated without medical intervention. CONCLUSION:
      Sublingual nitroglycerin improves the coronary diameter, the number of assessable
      segments, image quality and diagnostic accuracy of coronary CT angiography
      without major side effects or systemic physiological changes. KEY POINTS: *
      Sublingual nitroglycerin administration results in significant coronary artery
      dilatation. * Nitroglycerin increases the number of evaluable coronary branches.
      * Image quality is improved the most in smaller coronary branches. *
      Nitroglycerin increases the diagnostic accuracy of coronary CT angiography. *
      Most side effects are mild and do not require medical intervention.

PMID- 25994193
TI  - Thermal ablation of colorectal liver metastases: a position paper by an
      international panel of ablation experts, The Interventional Oncology Sans
      Frontieres meeting 2013.
AB  - OBJECTIVES: Previous attempts at meta-analysis and systematic review have not
      provided clear recommendations for the clinical application of thermal ablation
      in metastatic colorectal cancer. Many authors believe that the probability of
      gathering randomised controlled trial (RCT) data is low. Our aim is to provide a
      consensus document making recommendations on the appropriate application of
      thermal ablation in patients with colorectal liver metastases. METHODS: This
      consensus paper was discussed by an expert panel at The Interventional Oncology
      Sans Frontieres 2013. A literature review was presented. Tumour characteristics,
      ablation technique and different clinical applications were considered and the
      level of consensus was documented. RESULTS: Specific recommendations are made
      with regard to metastasis size, number, and location and ablation technique. Mean
      31 % 5-year survival post-ablation in selected patients has resulted in
      acceptance of this therapy for those with technically inoperable but limited
      liver disease and those with limited liver reserve or co-morbidities that render
      them inoperable. CONCLUSIONS: In the absence of RCT data, it is our aim that this
      consensus document will facilitate judicious selection of the patients most
      likely to benefit from thermal ablation and provide a unified interventional
      oncological perspective for the use of this technology. KEY POINTS: * Best
      results require due consideration of tumour size, number, volume and location. *
      Ablation technology, imaging guidance and intra-procedural imaging assessment
      must be optimised. * Accepted applications include inoperable disease due to
      tumour distribution or inadequate liver reserve. * Other current indications
      include concurrent co-morbidity, patient choice and the test-of-time approach. *
      Future applications may include resectable disease, e.g. for small solitary
      tumours.

PMID- 25994195
TI  - Extra-ocular muscle MRI in genetically-defined mitochondrial disease.
AB  - OBJECTIVES: Conventional and quantitative MRI was performed in patients with
      chronic progressive external ophthalmoplegia (CPEO), a common manifestation of
      mitochondrial disease, to characterise MRI findings in the extra-ocular muscles
      (EOMs) and investigate whether quantitative MRI provides clinically relevant
      measures of disease. METHODS: Patients with CPEO due to single mitochondrial DNA
      deletions were compared with controls. Range of eye movement (ROEM) measurements,
      peri-orbital 3 T MRI T1-weighted (T1w) and short-tau-inversion-recovery (STIR)
      images, and T2 relaxation time maps were obtained. Blinded observers graded
      muscle atrophy and T1w/STIR hyperintensity. Cross-sectional areas and EOM mean
      T2s were recorded and correlated with clinical parameters. RESULTS: Nine patients
      and nine healthy controls were examined. Patients had reduced ROEM (patients 13.3
      degrees , controls 49.3 degrees , p < 0.001), greater mean atrophy score and
      increased T1w hyperintensities. EOM mean cross-sectional area was 43 % of
      controls and mean T2s were prolonged (patients 75.6 +/- 7.0 ms, controls 55.2 +/-
      4.1 ms, p < 0.001). ROEM correlated negatively with EOM T2 (rho = -0.89, p <
      0.01), whilst cross-sectional area failed to correlate with any clinical
      measures. CONCLUSIONS: MRI demonstrates EOM atrophy, characteristic signal
      changes and prolonged T2 in CPEO. Correlation between elevated EOM T2 and ROEM
      impairment represents a potential measure of disease severity that warrants
      further evaluation. KEY POINTS: Chronic progressive external ophthalmoplegia is a
      common clinical manifestation of mitochondrial disease. * Existing extra-ocular
      muscle MRI data in CPEO reports variable radiological findings. MRI confirmed EOM
      atrophy and characteristic signal changes in CPEO. EOM T2 was significantly
      elevated in CPEO and correlated negatively with ocular movements. EOM T2
      represents a potential quantitative measure of disease severity in CPEO.

PMID- 25994196
TI  - Feasibility of three-dimensional ultrashort echo time magnetic resonance imaging
      at 1.5 T for the diagnosis of skull fractures.
AB  - OBJECTIVES: To investigate the feasibility of ultrashort echo time (UTE) magnetic
      resonance imaging (MRI) for the diagnosis of skull fractures. METHODS: The skull
      fracture models of ten Bama pigs and 364 patients with craniocerebral trauma were
      subjected to computed tomography (CT), UTE and conventional MRI sequences. The
      accuracy of UTE imaging in skull fracture diagnosis was analysed using receiver
      operating characteristic (ROC) curve analysis, McNemar's test and Kappa values.
      Differences among CT, UTE imaging and anatomical measurement (AM) values for
      linear fractures (LFs) and depressed fractures (DFs) were compared using one-way
      ANOVA and a paired-samples t-test. RESULTS: UTE imaging clearly demonstrated
      skull structures and fractures. The accuracy, validity and reliability of UTE MRI
      were excellent, with no significant differences between expert readings (P >
      0.05; Kappa, 0.899). The values obtained for 42 LFs and 13 DFs in the ten
      specimens were not significantly different among CT, UTE MRI and AMs, while those
      obtained for 55 LFs and ten DFs in 44 patients were not significantly different
      between CT and UTE MRI (P > 0.05). CONCLUSIONS: UTE MRI sequences are feasible
      for the evaluation of skull structures and fractures, with no radiation exposure,
      particularly for paediatric and pregnant patients. KEY POINTS: Despite ionising
      radiation, CT is standard for skull fracture assessment. Conventional MRI cannot
      depict skull structures. 3D-UTE sequences clearly demonstrate skull structures
      and fractures. UTE plus conventional MRI are superior to CT in craniocerebral
      trauma assessment. Paediatric and pregnant patients will benefit from this
      imaging modality.

PMID- 25994197
TI  - Clinicoradiological outcomes of 33 cases of surgically resected pulmonary
      pleomorphic carcinoma: correlation with prognostic indicators.
AB  - OBJECTIVES: To retrospectively review the clinical, radiological and pathological
      data in patients who underwent surgical resection for pulmonary pleomorphic
      carcinoma (PC), and to analyse the prognostic predictors of survival. METHODS:
      The data were retrospectively examined for 33 consecutive patients (28 males and
      five females) who had undergone surgical resection for pulmonary PC. Cox's
      proportional-hazards model was used to analyse the prognostic predictors of
      survival. RESULTS: The size of the tumours ranged from 1.1 to 12.0 cm (mean 5.4
      cm). The majority (26) of the tumours were located at the lung periphery, five
      tumours had cavitation, two had calcification and 14 had peritumoral ground-glass
      opacity. Most of the tumours showed heterogeneous enhancement and contained a low
      density area (LDA) within the tumour. The 5-year overall survival of surgically
      resected PC was 36 % (standard error = 0.093). A multivariate analysis revealed
      the LDA grade [hazard ratio (HR), 2.019], pathological stage (HR, 7.552) and
      pathological N factor (HR, 0.370) to be significant predictors of a poorer
      prognosis. CONCLUSIONS: A greater component of LDA within the tumour on contrast
      enhanced CT is associated with a poorer prognosis in patients with PC. KEY
      POINTS: PC has a poorer prognosis than other conventional NSCLC. The five-year OS
      of surgically resected PC was 36 %. A greater component of LDA on contrast
      enhanced CT suggests a poorer prognosis.

PMID- 25994198
TI  - Radiologic-pathologic analysis of quantitative 3D tumour enhancement on contrast
      enhanced MR imaging: a study of ROI placement.
AB  - OBJECTIVES: To investigate the influence of region-of-interest (ROI) placement on
      3D tumour enhancement [Quantitative European Association for the Study of the
      Liver (qEASL)] in hepatocellular carcinoma (HCC) patients treated with
      transcatheter arterial chemoembolization (TACE). METHODS: Phase 1: 40 HCC
      patients had nine ROIs placed by one reader using systematic techniques (3
      ipsilateral to the lesion, 3 contralateral to the lesion, and 3 dispersed
      throughout the liver) and qEASL variance was measured. Intra-class correlations
      were computed. Phase 2: 15 HCC patients with histosegmentation were selected. Six
      ROIs were systematically placed by AC (3 ROIs ipsilateral and 3 ROIs
      contralateral to the lesion). Three ROIs were placed by 2 radiologists. qEASL
      values were compared to histopathology by Pearson's correlation, linear
      regression, and median difference. RESULTS: Phase 1: The dispersed method
      (abandoned in phase 2) had low consistency and high variance. Phase 2: qEASL
      correlated strongly with pathology in systematic methods [Pearson's correlation
      coefficient = 0.886 (ipsilateral) and 0.727 (contralateral)] and in clinical
      methods (0.625 and 0.879). However, ipsilateral placement matched best with
      pathology (median difference: 5.4 %; correlation: 0.89; regression CI: [0.904,
      0.1409]). CONCLUSIONS: qEASL is a robust method with comparable values among
      tested placements. Ipsilateral placement showed high consistency and better
      pathological correlation. KEY POINTS: Ipsilateral and contralateral ROI placement
      produces high consistency and low variance. Both ROI placement methods produce
      qEASL values that correlate well with histopathology. Ipsilateral ROI placement
      produces best correlation to pathology along with high consistency.

PMID- 25994200
TI  - Access to shade changes behavioral and physiological attributes of dairy cows
      during the hot season in the subtropics.
AB  - The effect of shade on behavior and physiological attributes of grazing cows in a
      high altitude subtropical zone is not well established. This work aimed to
      investigate how social and ingestive behaviors, as well as physiological and
      other attributes of dairy cows such as milk production, change in a subtropical
      environment during the hot season either with or without free access to shade.
      Fourteen lactating cows were kept on pasture either with no shade or with free
      access to shade for 5 days and their behavior was recorded with instantaneous
      scan sampled every 10 min, from sunrise, 0530 h (Greenwich mean time, GMT-0200 h)
      to sunset, 2100 h (GMT-0200 h). Behavior traits included (1) time spent in
      activities such as grazing, ruminating, resting, lying, standing, walking,
      seeking shade and staying in the proximity to the water trough and (2) number of
      events such as water ingestion, aggressive interactions, as well as competition
      for shade and water. Physiological attributes such as heart and respiratory
      rates, rectal temperature, number of rumen movements, panting score, as well as
      milk yield, were evaluated. Time spent in behavioral activities, number of
      behavioral events and physiological attributes varied between groups (with and
      without access to shade). Cows with no shade showed increased respiratory and
      heart rates and panting score at 1300 h, higher values for time of permanence
      near the water trough, number of competition and aggression events for shade. On
      the other hand, they showed lower values for time spent resting while lying,
      ruminating while standing, seeking shade. Access to shade did not change time
      spent lying, standing, walking with the head up, ruminating while lying, resting
      while standing, as well as milk yield and number of ruminal movements.
      Significant interactions between access to shade and days of measurements were
      detected for time spent walking, ruminating, grazing, resting, number of water
      ingestion events, competition events near the water trough and for shade, as well
      as for rectal temperature and panting score measured at 1700 h. In the high
      altitude subtropical region, access to shade minimizes negative heat stress
      effects on behavior and physiological aspects of dairy cows. 

PMID- 25994199
TI  - 256-Slice coronary computed tomographic angiography in patients with atrial
      fibrillation: optimal reconstruction phase and image quality.
AB  - OBJECTIVES: To assess the optimal reconstruction phase and the image quality of
      coronary computed tomographic angiography (CCTA) in patients with atrial
      fibrillation (AF). METHODS: We performed CCTA in 60 patients with AF and 60
      controls with sinus rhythm. The images were reconstructed in multiple phases in
      all parts of the cardiac cycle, and the optimal reconstruction phase with the
      fewest motion artefacts was identified. The coronary artery segments were
      visually evaluated to investigate their assessability. RESULTS: In 46 (76.7 %)
      patients, the optimal reconstruction phase was end-diastole, whereas in 6 (10.0
      %) patients it was end-systole or mid-diastole, and in 2 (3.3 %) patients it was
      another cardiac phase. In 53 (88.3 %) of the controls, the optimal reconstruction
      phase was mid-diastole, whereas it was end-systole in 4 (6.7 %), and in 3 (5.0 %)
      it was another cardiac phase. There was a significant difference between patients
      with AF and the controls in the optimal phase (p < 0.01) but not in the visual
      image quality score (p = 0.06). CONCLUSIONS: The optimal reconstruction phase in
      most patients with AF was the end-diastolic phase. The end-systolic phase tended
      to be optimal in AF patients with higher average heart rates. KEY POINTS: The
      optimal reconstruction phase in 76.7 % of patients with atrial fibrillation (AF)
      was end-diastole. The end-systolic phase was optimal in AF patients with higher
      heart rates. ECG and heart-rate control are necessary to obtain end-diastolic
      images with fewer motion artefacts.

PMID- 25994201
TI  - Nanopore analysis of amyloid fibrils formed by lysozyme aggregation.
AB  - The measurement of single particle size distributions of amyloid fibrils is
      crucial for determining mechanisms of growth and toxicity. Nanopore sensing is an
      attractive solution for this problem since it gives information on aggregates'
      shapes with relatively high throughput for a single particle technology. In this
      paper we study the translocation of lysozyme fibrils through quartz glass
      nanopores. We demonstrate that, under appropriate salt and pH conditions,
      lysozyme fibrils translocate through bare quartz nanopores without causing
      significant clogging. This enables us to measure statistics on tens of thousands
      of translocations of lysozyme fibrils with the same nanopore and track their
      development over a time course of aggregation spanning 24 h. Analysis of our
      events shows that the statistics are consistent with a simple bulk conductivity
      model for the passage of rods with a fixed cross sectional area through a conical
      glass nanopore. 

PMID- 25994203
TI  - beta-hCG resolution times during expectant management of tubal ectopic
      pregnancies.
AB  - BACKGROUND: A subset of women with a tubal ectopic pregnancy can be safely
      managed expectantly. Expectant management involves a degree of disruption with
      hospital visits to determine serum beta-hCG (beta-human chorionic gonadotrophin)
      concentration until the pregnancy test becomes negative and expectant management
      is considered complete. The length of time required for the pregnancy test to
      become negative and the parameters that influence this interval have not been
      described. Information on the likely length of follow up would be useful for
      women considering expectant management of their tubal ectopic pregnancy. METHODS:
      This was a retrospective study at a tertiary referral center in an inner city
      London Hospital. We included women who were diagnosed with a tubal ectopic
      pregnancy by transvaginal ultrasound between March 2009 and March 2014. During
      the study period 474 women were diagnosed with a tubal ectopic pregnancy and 256
      (54 %) of them fulfilled our management criteria for expectant management. A
      total of 158 (33 %) women had successful expectant management and in those cases
      we recorded the diameter of the ectopic pregnancy (mm), the maximum serum beta
      hCG (IU/L) and levels during follow up until resolution as well as the interval
      to resolution (days). RESULTS: The median interval from maximum serum beta-hCG
      concentration to resolution was 18.0 days (IQR 11.0-28.0). The maximum serum beta
      hCG concentration and the rate of decline of beta-hCG were independently
      associated with the length of follow up. Women's age and size of ectopic
      pregnancy did not have significant effects on the length of follow up.
      CONCLUSION: Women undergoing expectant management of ectopic pregnancy can be
      informed that the likely length of follow up is under 3 weeks and that it
      positively correlates with initial beta-hCG level at the time of diagnosis.

PMID- 25994204
TI  - Fabrication and optical characterization of large scale membrane containing
      InP/AlGaInP quantum dots.
AB  - Single-photon sources with a high extraction efficiency are a prerequisite for
      applications in quantum communication and quantum computation schemes. One
      promising approach is the fabrication of a quantum dot containing membrane
      structure in combination with a solid immersion lens and a metal mirror. We have
      fabricated an 80 nm thin semiconductor membrane with incorporated InP quantum
      dots in an AlGaInP double hetero barrier via complete substrate removal. In
      addition, a gold layer was deposited on one side of the membrane acting as a
      mirror. The optical characterization shows in detail that the unique properties
      of the quantum dots are preserved in the membrane structure. 

PMID- 25994202
TI  - Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1
      inhibition.
AB  - BACKGROUND: The hypoxia-activated prodrug TH-302 is reduced at its nitroimidazole
      group and selectively under hypoxic conditions releases the DNA cross-linker
      bromo-isophosphoramide mustard (Br-IPM). Here, we have explored the effect of
      Chk1 inhibition on TH-302-mediated pharmacological activities. METHODS: We
      employed in vitro cell viability, DNA damage, cellular signaling assays and the
      in vivo HT29 human tumor xenograft model to study the effect of Chk1inhibition on
      TH-302 antitumor activities. RESULTS: TH-302 cytotoxicity is greatly enhanced by
      Chk1 inhibition in p53-deficient but not in p53-proficient human cancer cell
      lines. Chk1 inhibitors reduced TH-302-induced cell cycle arrest via blocking TH
      302-induced decrease of phosphorylation of histone H3 and increasing Cdc2-Y15
      phosphorylation. Employing the single-cell gel electrophoresis (comet) assay, we
      observed a potentiation of the TH-302 dependent tail moment. TH-302 induced
      gammaH2AX and apoptosis were also increased upon the addition of Chk1 inhibitor.
      Potentiation of TH-302 cytotoxicity by Chk1 inhibitor was only observed in cell
      lines proficient in, but not deficient in homology-directed DNA repair. We also
      show that combination treatment led to lowering of Rad51 expression levels as
      compared to either agent alone. In vivo data demonstrate that Chk1 inhibitor
      enhances TH-302 anti-tumor activity in p53 mutant HT-29 human tumor xenografts,
      supporting the hypothesis that these in vitro results can translate to enhanced
      in vivo efficacy of the combination. CONCLUSIONS: TH-302-mediated in vitro and in
      vivo anti-tumor activities were greatly enhanced by the addition of Chk1
      inhibitors. The preclinical data presented in this study support a new approach
      for the treatment of p53-deficient hypoxic cancers by combining Chk1 inhibitors
      with the hypoxia-activated prodrug TH-302.

PMID- 25994205
TI  - A simple method for establishing an ostrich model of femoral head osteonecrosis
      and collapse.
AB  - BACKGROUND: This study aimed to develop a simple method of creating an animal
      model of non-trauma femoral head osteonecrosis and collapse using African
      ostriches with weights similar to those of humans. METHODS: Eighteen African
      ostriches were subjected to liquid nitrogen cryo-insult in the unilateral femoral
      head through surgical procedures using homemade cryogenic equipment combined with
      tract drilling inside the femoral head. Three animals were sacrificed at
      postoperative weeks 6 and 12, respectively, and the remaining animals were
      sacrificed at postoperative week 24. Bilateral femoral heads were harvested and
      subjected to gross observation, histological examination using hematoxylin and
      eosin staining, and radiographic examination. Micro-computed tomography was
      performed on a portion of the specimens at postoperative week 24, and
      angiographic examination of the femoral head was performed before sacrificing the
      animals. RESULTS: Eight ostriches developed a limp at postoperative week 8, with
      a mean duration of 16.5 weeks. The postoperative femoral head specimens showed
      changes in contour and articular cartilage degeneration. Sagittal sectioning of
      the collapsed femoral head specimens revealed distinct boundaries among the
      osteonecrotic areas, osteosclerotic areas, and normal trabeculae. Histological
      examinations revealed active bone resorption in the osteonecrotic area of the
      subchondral bone, an increased number of fat cells, and active trabecular bone
      regeneration in the osteosclerotic areas. The postoperative radiographic
      examinations revealed that the height of the femoral head gradually decreased and
      progressed to collapse. Micro-computed tomography scans showed the interrupted
      trabecular bone with an irregular shape in the collapsed femoral head. Compared
      with the normal samples, angiographic findings revealed interrupted blood supply
      of the cryo-injured samples in some areas of the femoral heads, blood vessel
      narrowing, and decreased number of blood vessels in the cryo-injured areas.
      CONCLUSION: This study indicates that an animal model of osteonecrotic femoral
      head progressing to collapse can be established via a simplified method of
      cryosurgery. This model possesses histological features that are similar to those
      of humans; thus, it can be used as an ideal animal model for the study of femoral
      head necrosis.

PMID- 25994206
TI  - Neuroprotective effects of Eucommia ulmoides Oliv. and its bioactive constituent
      work via ameliorating the ubiquitin-proteasome system.
AB  - BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder
      characterized by a loss of dopaminergic neurons in the substantia nigra,
      decreased striatal dopamine levels, and consequent extrapyramidal motor
      dysfunction. The purpose of this study was to investigate potential in vivo
      protective effects of Duzhong against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), as well as the bioactive constituents against 1-methyl
      4-phenylpyridinium (MPP(+)) toxicity in vitro. METHODS: Male C57BL/6 mice were
      intraperitoneally administrated five consecutive injections of MPTP every 24 h at
      a dose of 30 mg/kg to induce an in vivo PD model. Pole and traction tests were
      performed in mice to evaluate motor deficits and bradykinesia after the final
      MPTP administration. The striatal levels of dopamine and its metabolites, 3,4
      dihydroxyphenylacetic acid and homovanilic acid, were measured using a High
      performance liquid chromatography-electrical conductivity detector. To further
      explore the bioactive constituents and protective mechanisms of Duzhong, seven
      compounds from Duzhong were tested on MPP(+)-treated SH-SY5Y cell lines in vitro.
      A proteasome enzymatic assay and Cell Counting Kit-8 were performed to examine
      proteasomal activity and cell viability of Duzhong-treated cells, respectively,
      after exposure to MPP(+) and proteasome inhibitor MG132. RESULTS: Duzhong
      antagonized the loss of striatal neurotransmitters and relieved the associated
      anomaly in ambulatory locomotor activity in PD mice after a 3-day pre-treatment
      of Duzhong crude extract. The five Duzhong compounds attenuated MPP(+)-induced
      dysfunction of protease activity and reduced MG132-induced cytotoxicity.
      CONCLUSION: Duzhong could serve as a potential candidate for PD treatment, and
      its mechanism involves the amelioration of the ubiquitin-proteasome system.

PMID- 25994207
TI  - What does the beck depression inventory measure in myocardial infarction
      patients? a psychometric approach using item response theory and person-fit.
AB  - Observed associations between depression following myocardial infarction (MI) and
      adverse cardiac outcomes could be overestimated due to patients' tendency to over
      report somatic depressive symptoms. This study was aimed to investigate this
      issue with modern psychometrics, using item response theory (IRT) and person-fit
      statistics to investigate if the Beck Depression Inventory (BDI) measures
      depression or something else among MI-patients. An IRT-model was fit to BDI-data
      of 1135 MI patients. Patients' adherence to this IRT-model was investigated with
      person-fit statistics. Subgroups of "atypical" (low person-fit) and
      "prototypical" (high person-fit) responders were identified and compared in terms
      of item-response patterns, psychiatric diagnoses, socio-demographics and somatic
      factors. In the IRT model, somatic items had lower thresholds compared to
      depressive mood/cognition items. Empirically identified "atypical" responders (n
      = 113) had more depressive mood/cognitions, scored lower on somatic items and
      more often had a Comprehensive International Diagnostic Interview (CIDI)
      depressive diagnosis than "prototypical" responders (n = 147). Additionally,
      "atypical" responders were younger and more likely to smoke. In conclusion, the
      BDI measures somatic symptoms in most MI patients, but measures depression in a
      subgroup of patients with atypical response patterns. The presented approach to
      account for interpersonal differences in item responding could help improve the
      validity of depression assessments in somatic patients.

PMID- 25994208
TI  - Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of
      Lymph Node Status in Extrahepatic Cholangiocarcinoma.
AB  - BACKGROUND: This study aimed to compare the utility of the number of positive
      lymph nodes with the lymph node ratio (LNR) in predicting survival after
      resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis
      of 142 consecutive patients who underwent radical resection of extrahepatic
      cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were
      resected. The median number of nodes per patient was 21. The optimal cutoff
      values for the number of positive nodes and the LNR were determined using the Chi
      square scores calculated by the Cox proportional hazards regression model.
      RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent
      analysis of the impact that nodal status has on survival, 18 patients with R1/2
      resection and 6 patients with paraaortic nodal disease who did not survive for
      more than 5 years after resection were excluded. The optimal cutoff value for the
      number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %.
      Univariate analysis identified both the number of positive nodes (0, 1, or >=2; P
      = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic
      factors. Multivariate analysis identified the number of positive nodes but not
      the LNR as an independent prognostic factor (P = 0.012). The 5-year survival
      rates were 64 % for the patients with no positive nodes, 46 % for the patients
      with one positive node, and 28 % for the patients with two or more positive
      nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better
      than the LNR after resection of extrahepatic cholangiocarcinoma, provided that
      nodal evaluation is sufficient.

PMID- 25994209
TI  - Comparison of Mammographic Findings Following Oncoplastic Mammoplasty and
      Lumpectomy Without Reconstruction.
AB  - BACKGROUND: Reconstruction of lumpectomy defects with reduction mammoplasty
      techniques can improve aesthetic outcomes and patient satisfaction. However, one
      concern with the substantial tissue rearrangement required is the possible
      difficulty with mammographic follow up and/or increased recommendations for
      future biopsies. METHODS: We performed a retrospective review of 49 patients who
      underwent oncoplastic reduction mammoplasty between 2001 and 2009 who were age
      matched to patients who underwent lumpectomy without reconstruction. Mammography
      reports at 6 months, 1, 2, and 5 years postoperatively were reviewed for
      predominant findings, Breast Imaging Reporting and Data System final assessments,
      and recommendations for biopsy. RESULTS: There was no significant difference in
      abnormal mammographic findings prompting biopsy between the two cohorts at 6
      months, 2 years, and 5 years postoperatively (p > 0.05). Biopsy rates over the 5
      year period did not differ significantly between the two cohorts [9 (18 %)
      lumpectomy cohort, 12 (24 %) oncoplastic cohort, p = 0.46]. Overall cancer-to
      biopsy ratio was 33 % in the lumpectomy cohort and 42 % in the oncoplastic cohort
      (p = 1.00). CONCLUSIONS: Although substantial tissue rearrangement is performed
      at the time of oncoplastic reduction mammoplasty, our results reveal no increased
      incidence of postoperative mammographic abnormalities or unnecessary biopsies
      compared to lumpectomy alone. This demonstrates that fear of increasing
      mammographic abnormalities and biopsies after reduction mammoplasty is unfounded
      and should not prevent utilization of this technique if it can optimize cosmetic
      outcomes and extend the option of breast conservation.

PMID- 25994210
TI  - Survival of Patients with Uterine Carcinosarcoma Undergoing Sentinel Lymph Node
      Mapping.
AB  - PURPOSE: This study was designed to evaluate the outcome of patients with uterine
      carcinosarcoma undergoing sentinel lymph node (SLN) mapping. METHODS: A
      prospectively maintained database was reviewed for all women with uterine cancer
      treated at our institution from January 1, 1998 to August 31, 2014. Patients were
      grouped based on whether they had undergone SLN mapping or routine
      lymphadenectomy at the time of staging. SLN evaluation was performed according to
      a standard institutional protocol that incorporates a surgical algorithm and
      pathologic ultrastaging. RESULTS: We identified 136 patients with uterine
      carcinosarcoma who had undergone lymph node evaluation; 48 had surgical staging
      with SLN mapping and 88 had routine lymphadenectomy consisting of pelvic and/or
      para-aortic lymph node dissection. Stage distribution for the SLN group included:
      stage I, 31 (65 %); stage II, 1 (2 %); stage III, 11 (23 %); stage IV, 5 (10 %).
      Stage distribution for the non-SLN group included: stage I, 48 (55 %); stage II,
      4 (4 %); stage III, 19 (22 %); stage IV, 17 (19 %) (p = 0.4). Median number of
      lymph nodes removed was 8 and 20, respectively (p <= 0.001). Median number of
      positive nodes was similar between the groups (p = 0.2). Of the 67 patients who
      had a documented recurrence, 14 of 20 (70 %) in the SLN and 34 of 47 (74 %) in
      the non-SLN group demonstrated a distant/multifocal pattern of recurrence. There
      was no difference in median progression-free survival between the groups (23 vs.
      23.2 months, respectively; p = 0.7). CONCLUSIONS: Progression-free survival in
      women with uterine carcinosarcoma undergoing SLN mapping with adjuvant therapy
      appears similar to that of patients treated before the incorporation of the SLN
      protocol. Additional prospective studies with longer follow-up are necessary to
      validate these early results.

PMID- 25994211
TI  - Bilateral Mastectomy: Doubling Down on Complications?

PMID- 25994212
TI  - Cost-effectiveness of the Mental Health and Development model for schizophrenia
      spectrum and bipolar disorders in rural Kenya.
AB  - BACKGROUND: The treatment gap for serious mental disorders across low-income
      countries is estimated to be 89%. The model for Mental Health and Development
      (MHD) offers community-based care for people with mental disorders in 11 low- and
      middle-income countries. METHOD: In Kenya, using a pre-post design, 117
      consecutively enrolled participants with schizophrenia-spectrum and bipolar
      disorders were followed-up at 10 and 20 months. Comparison outcomes were drawn
      from the literature. Costs were analysed from societal and health system
      perspectives. RESULTS: From the societal perspective, MHD cost Int$ 594 per
      person in the first year and Int$ 876 over 2 years. The cost per healthy day
      gained was Int$ 7.96 in the first year and Int$ 1.03 over 2 years - less than the
      agricultural minimum wage. The cost per disability-adjusted life year averted
      over 2 years was Int$ 13.1 and Int$ 727 from the societal and health system
      perspectives, respectively, on par with antiretrovirals for HIV. CONCLUSIONS: MHD
      achieved increasing returns over time. The model appears cost-effective and
      equitable, especially over 2 years. Its affordability relies on multi-sectoral
      participation nationally and internationally.

PMID- 25994213
TI  - Layer-controllable WS2-reduced graphene oxide hybrid nanosheets with high
      electrocatalytic activity for hydrogen evolution.
AB  - In this study, an efficient poly(vinylpyrrolidone) (PVP)-assisted hydrothermal
      method for the in situ growth of WS2 nanosheets with layer-controllability on
      reduced graphene oxide (rGO) is reported. The number of layers (from a monolayer
      to ~25 layers) of the exfoliated WS2 can be accurately controlled by adjusting
      the amount of PVP. The layer structure and the morphology of the as-prepared
      hybrids are confirmed by field emission scanning electron microscopy and high
      resolution transmission microscopy. The X-ray diffraction, Raman, and X-ray
      photoemission spectroscopy of the obtained WS2-rGO hybrid nanosheets indicate
      highly crystallized structures, a clear Raman shift and a stoichiometry, which is
      dependent on the number of layers. Furthermore, these highly active and durable
      catalysts exhibit an electrocatalytic current density of 10 mA cm(-2) at a small
      hydrogen evolution reaction (HER) overpotential (-170 mV) and a Tafel slope of 52
      mV dec(-1) with an excellent electrocatalytic stability (after 6 months storage).

PMID- 25994214
TI  - Plasma complement factor H is associated with disease activity of patients with
      ANCA-associated vasculitis.
AB  - INTRODUCTION: Increasing evidences have demonstrated that activation of
      alternative complement pathway plays an important role in the pathogenesis of
      anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The
      current study aimed to investigate the association of complement factor H (CFH),
      a key regulator of the alternative complement pathway, with the disease activity
      of AAV. METHODS: Plasma CFH levels were measured in 82 patients with
      myeloperoxidase (MPO)-AAV in active stage. Of the 82 patients, plasma CFH levels
      of 27 patients were longitudinally measured. Serum anti-CFH autoantibodies were
      screened in AAV patients. Circulating complement activation profiles including
      C4d, Bb, C3a, C5a and soluble C5b-9 of AAV patients in active stage were further
      detected. Associations between plasma CFH levels and clinicopathological
      parameters as well as the prognosis were analyzed. RESULTS: Plasma CFH levels
      were significantly lower in active AAV patients compared with AAV patients in
      remission and normal controls. Correlation analysis showed that plasma CFH levels
      inversely correlated with initial serum creatinine, Birmingham Vasculitis
      Activity Score (BVAS), proportion of total crescents and cellular crescents in
      renal specimens, and circulating levels of C3a, C5a and Sc5b-9, meanwhile
      positively correlated with estimated glomerular filtration rate (eGFR),
      hemoglobin levels and circulating levels of C3. Moreover, multivariate survival
      analysis revealed that plasma CFH levels were independently associated with
      composite outcome of death or end stage renal disease (ESRD) in AAV patients,
      after adjusting for age, gender, hemoglobin level and urinary protein (P = 0.03,
      HR 0.85, 95 % CI 0.73-0.98) or adjusting for age, gender, total crescents (%) and
      urinary protein (P = 0.03, HR 0.85, 95 % CI 0.73-0.98), while not as an
      independent predictor after adjusting for age, gender, serum creatinine and
      urinary protein (P = 0.57, HR 0.96, 95 % CI 0.83-1.11). CONCLUSION: In
      conclusion, plasma CFH levels are associated with disease activity, and, to some
      extent, associated with composite outcomes of patients with MPO-ANCA-associated
      vasculitis.

PMID- 25994215
TI  - Global transcription of CRISPR loci in the human oral cavity.
AB  - BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)
      are active in acquired resistance against bacteriophage and plasmids in a number
      of environments. In the human mouth, CRISPR loci evolve to counteract oral phage,
      but the expression of these CRISPR loci has not previously been investigated. We
      sequenced cDNA from CRISPR loci found in numerous different oral bacteria and
      compared with oral phage communities to determine whether the transcription of
      CRISPR loci is specifically targeted towards highly abundant phage present in the
      oral environment. RESULTS: We found that of the 529,027 CRISPR spacer groups
      studied, 88 % could be identified in transcripts, indicating that the vast
      majority of CRISPR loci in the oral cavity were transcribed. There were no strong
      associations between CRISPR spacer repertoires and oral health status or nucleic
      acid type. We also compared CRISPR repertoires with oral bacteriophage
      communities, and found that there was no significant association between CRISPR
      transcripts and oral phage, regardless of the CRISPR type being evaluated. We
      characterized highly expressed CRISPR spacers and found that they were no more
      likely than other spacers to match oral phage. By reassembling the CRISPR-bearing
      reads into longer CRISPR loci, we found that the majority of the loci did not
      have spacers matching viruses found in the oral cavities of the subjects studied.
      For some CRISPR types, loci containing spacers matching oral phage were
      significantly more likely to have multiple spacers rather than a single spacer
      matching oral phage. CONCLUSIONS: These data suggest that the transcription of
      oral CRISPR loci is relatively ubiquitous and that highly expressed CRISPR
      spacers do not necessarily target the most abundant oral phage.

PMID- 25994216
TI  - Analysis of pre-test interviews in a cohort of Brazilian patients with movement
      disorders.
AB  - Spinocerebellar ataxias and Huntington disease are heritable, adult onset,
      neurodegenerative disorders of movement. Both are autosomal dominant and caused
      by expansions in trinucleotide sequences in several genes. Because these
      expansions are associated with an almost complete penetrance, genetic tests are
      available at the diagnostic and predictive level. In this study, we describe the
      expectations and issues raised during pre-test interviews for genetic counselling
      for these diseases. Data from pre-test interviews with 97 patients and at-risk
      relatives for spinocerebellar ataxia (SCA) or Huntington disease was comprised of
      close-ended questions (demographics, personal and current disease history) and
      open-ended questions, where individuals were asked to describe their hopes and
      expectations on the genetic counselling evaluation and also their degree of
      knowledge about genetics and medical genetics. Amongst the main expectations
      identified in patients and at-risk relatives, issues related to the aetiological
      diagnosis and/or disclosure of the at-risk status were those most frequently
      mentioned (57 %). Improvement in quality of life was another identified issue (17
      %). Interestingly, the issue of inheritance/transmission was identified as the
      main expectation by a minority of individuals (3 %). Pre-test interviews are
      valuable tools to identify issues raised by consultands and promote a better
      communication between the patient, family and the genetic counselling team. 

PMID- 25994217
TI  - Stromal biology and therapy in pancreatic cancer: a changing paradigm.
AB  - Pancreatic ductal adenocarcinoma (PDA) exhibits one of the poorest prognosis of
      all solid tumours and poses an unsolved problem in cancer medicine. Despite the
      recent success of two combination chemotherapies for palliative patients, the
      modest survival benefits are often traded against significant side effects and a
      compromised quality of life. Although the molecular events underlying the
      initiation and progression of PDA have been intensively studied and are
      increasingly understood, the reasons for the poor therapeutic response are hardly
      apprehended. One leading hypothesis over the last few years has been that the
      pronounced tumour microenvironment in PDA not only promotes carcinogenesis and
      tumour progression but also mediates therapeutic resistance. To this end,
      targeting of various stromal components and pathways was considered a promising
      strategy to biochemically and biophysically enhance therapeutic response.
      However, none of the efforts have yet led to efficacious and approved therapies
      in patients. Additionally, recent data have shown that tumour-associated
      fibroblasts may restrain rather than promote tumour growth, reinforcing the need
      to critically revisit the complexity and complicity of the tumour-stroma with
      translational implications for future therapy and clinical trial design. 

PMID- 25994218
TI  - Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C.
AB  - OBJECTIVE: Congenital sodium diarrhoea (CSD) refers to a form of secretory
      diarrhoea with intrauterine onset and high faecal losses of sodium without
      congenital malformations. The molecular basis for CSD remains unknown. We
      clinically characterised a cohort of infants with CSD and set out to identify
      disease-causing mutations by genome-wide genetic testing. DESIGN: We performed
      whole-exome sequencing and chromosomal microarray analyses in 4 unrelated
      patients, followed by confirmatory Sanger sequencing of the likely disease
      causing mutations in patients and in their family members, followed by functional
      studies. RESULTS: We identified novel de novo missense mutations in GUCY2C, the
      gene encoding receptor guanylate cyclase C (GC-C) in 4 patients with CSD. One
      patient developed severe, early-onset IBD and chronic arthritis at 4 years of
      age. GC-C is an intestinal brush border membrane-bound guanylate cyclase, which
      functions as receptor for guanylin, uroguanylin and Escherichia coli heat-stable
      enterotoxin. Mutations in GUCY2C were present in different intracellular domains
      of GC-C, and were activating mutations that enhanced intracellular cyclic
      guanosine monophosphate accumulation in a ligand-independent and ligand
      stimulated manner, following heterologous expression in HEK293T cells.
      CONCLUSIONS: Dominant gain-of-function GUCY2C mutations lead to elevated
      intracellular cyclic guanosine monophosphate levels and could explain the chronic
      diarrhoea as a result of decreased intestinal sodium and water absorption and
      increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this
      receptor in the pathogenesis of sporadic CSD.

PMID- 25994219
TI  - Long non-coding RNA CCAL regulates colorectal cancer progression by activating
      Wnt/beta-catenin signalling pathway via suppression of activator protein 2alpha.
AB  - OBJECTIVE: Long non-coding RNAs (lncRNAs) are emerging as key molecules in
      cancers, yet their potential molecular mechanisms are not well understood. The
      objective of this study is to examine the expression and functions of lncRNAs in
      the development of colorectal cancer (CRC). METHODS: LncRNA expression profiling
      of CRC, adenoma and normal colorectal tissues was performed to identify tumour
      related lncRNAs involved in colorectal malignant transformation. Then, we used
      quantitative reverse transcription PCR assays to measure the tumour-related
      lncRNA and to assess its association with survival and response to adjuvant
      chemotherapy in 252 patients with CRC. The mechanisms of CCAL function and
      regulation in CRC were examined using molecular biological methods. RESULTS: We
      identified colorectal cancer-associated lncRNA (CCAL) as a key regulator of CRC
      progression. Patients whose tumours had high CCAL expression had a shorter
      overall survival and a worse response to adjuvant chemotherapy than patients
      whose tumours had low CCAL expression. CCAL promoted CRC progression by targeting
      activator protein 2alpha (AP-2alpha), which in turn activated Wnt/beta-catenin
      pathway. CCAL induced multidrug resistance (MDR) through activating Wnt/beta
      catenin signalling by suppressing AP-2alpha and further upregulating MDR1/P-gp
      expression. In addition, we found that histone H3 methylation and deacetylases
      contributed to the upregulation of CCAL in CRC. CONCLUSIONS: Our results suggest
      that CCAL is a crucial oncogenic regulator involved in CRC tumorigenesis and
      progression.

PMID- 25994220
TI  - Novel evidence for an oncogenic role of microRNA-21 in colitis-associated
      colorectal cancer.
AB  - OBJECTIVE: miR-21 was found to be overexpressed in the colon tissues and serum of
      patients with UC and colorectal cancer (CRC); however, the exact roles of miR-21
      in colitis-associated CRC remain unclear. The aim of our study was to investigate
      the biological mechanisms of miR-21 in colitis-associated colon cancer (CAC).
      DESIGN: miR-21 expression was examined in the tumours of 62 patients with CRC
      from China and 37 colitis-associated neoplastic tissues from Japan and Austria.
      The biological functions of miR-21 were studied using a series of in vitro, in
      vivo and clinical approaches. RESULTS: miR-21 levels were markedly upregulated in
      the tumours of 62 patients with CRC, 22 patients with CAC, and in a mouse model
      of CAC. Following azoxymethane and dextran sulfate sodium intervention, miR-21
      knockout mice showed reduced expression of proinflammatory and procarcinogenic
      cytokines (interleukin (IL) 6, IL-23, IL-17A and IL-21) and a decrease in the
      size and number of tumours compared with the control mouse group. The absence of
      miR-21 resulted in the reduced expression of Ki67 and the attenuated
      proliferation of tumour cells with a simultaneous increase in E-cadherin and
      decrease in beta-catenin and SOX9 in the tumours of CAC mice. Furthermore, the
      absence of miR-21 increased the expression of its target gene PDCD4 and
      subsequently modulated nuclear factor (NF)-kappaB activation. Meanwhile, miR-21
      loss reduced STAT3 and Bcl-2 activation, causing an increase in the apoptosis of
      tumour cells in CAC mice. CONCLUSIONS: These observations provide novel evidence
      for miR-21 blockade to be a key strategy in reducing CAC.

PMID- 25994222
TI  - Effect of Au nano-particle aggregation on the deactivation of the AuCl3/AC
      catalyst for acetylene hydrochlorination.
AB  - A detailed study of the valence state and distribution of the AuCl3/AC catalyst
      during the acetylene hydrochlorination deactivation process is described and
      discussed. Temperature-programmed reduction and X-ray photoelectron spectral
      analysis indicate that the active Au(3+) reduction to metallic Au(0) is one
      reason for the deactivation of AuCl3/AC catalyst. Transmission electron
      microscopy characterization demonstrated that the particle size of Au nano
      particles increases with increasing reaction time. The results indicated that
      metallic Au(0) exhibits considerable catalytic activity and that Au nano-particle
      aggregation may be another reason for the AuCl3/AC catalytic activity in
      acetylene hydrochlorination. 

PMID- 25994221
TI  - Molecular markers for colorectal cancer screening.
AB  - Colorectal cancer (CRC), although a significant cause of morbidity and mortality
      worldwide, has seen a declining incidence and mortality in countries with
      programmatic screening. Faecal occult blood testing and endoscopic approaches are
      the predominant screening methods currently. The discovery of the adenoma
      carcinoma sequence and a greater understanding of the genetic and epigenetic
      changes that drive the formation of CRC have contributed to innovative research
      to identify molecular markers for highly accurate, non-invasive screening tests
      for CRC. DNA, proteins, messenger RNA and micro-RNA have all been evaluated. The
      observation of tumour cell exfoliation into the mucocellular layer of the colonic
      epithelium and proven stability of DNA in a harsh stool environment make stool
      DNA a particularly promising marker. The development of a clinically useful stool
      DNA test has required numerous technical advances, including optimisation in DNA
      stabilisation, the development of assays with high analytical sensitivity, and
      the identification of specific and broadly informative molecular markers. A
      multitarget stool DNA test, which combines mutant and methylated DNA markers and
      a faecal immunochemical test, recently performed favourably in a large cross
      sectional validation study and has been approved by the US Food and Drug
      Administration for the screening of asymptomatic, average-risk individuals. The
      ultimate way in which molecular marker screening assays will be used in clinical
      practice will require additional studies to determine optimal screening
      intervals, factors affecting compliance, management of false-positive results,
      and the use of these assays in high-risk populations, as well as other
      considerations. 

PMID- 25994223
TI  - Climate change-induced vegetation change as a driver of increased subarctic
      biogenic volatile organic compound emissions.
AB  - Emissions of biogenic volatile organic compounds (BVOCs) have been earlier shown
      to be highly temperature sensitive in subarctic ecosystems. As these ecosystems
      experience rapidly advancing pronounced climate warming, we aimed to investigate
      how warming affects the BVOC emissions in the long term (up to 13 treatment
      years). We also aimed to assess whether the increased litterfall resulting from
      the vegetation changes in the warming subarctic would affect the emissions. The
      study was conducted in a field experiment with factorial open-top chamber warming
      and annual litter addition treatments on subarctic heath in Abisko, northern
      Sweden. After 11 and 13 treatment years, BVOCs were sampled from plant
      communities in the experimental plots using a push-pull enclosure technique and
      collection into adsorbent cartridges during the growing season and analyzed with
      gas chromatography-mass spectrometry. Plant species coverage in the plots was
      analyzed by the point intercept method. Warming by 2  degrees C caused a 2-fold
      increase in monoterpene and 5-fold increase in sesquiterpene emissions, averaged
      over all measurements. When the momentary effect of temperature was diminished by
      standardization of emissions to a fixed temperature, warming still had a
      significant effect suggesting that emissions were also indirectly increased. This
      indirect increase appeared to result from increased plant coverage and changes in
      vegetation composition. The litter addition treatment also caused significant
      increases in the emission rates of some BVOC groups, especially when combined
      with warming. The combined treatment had both the largest vegetation changes and
      the highest BVOC emissions. The increased emissions under litter addition were
      probably a result of a changed vegetation composition due to alleviated nutrient
      limitation and stimulated microbial production of BVOCs. We suggest that the
      changes in the subarctic vegetation composition induced by climate warming will
      be the major factor indirectly affecting the BVOC emission potentials and
      composition. 

PMID- 25994225
TI  - Correction.

PMID- 25994224
TI  - From Leaf Metabolome to In Vivo Testing: Identifying Antifeedant Compounds for
      Ecological Studies of Marsupial Diets.
AB  - Identifying specific plant secondary metabolites that influence feeding behavior
      can be challenging, but a solid understanding of animal preferences can guide
      efforts. Common brushtail possums (Trichosurus vulpecula) predominantly eat
      Eucalyptus species belonging to the subgenus Symphyomyrtus, and avoid eating
      those belonging to the Monocalyptus subgenus (also called subgenus Eucalyptus).
      Using an unbiased (1)H NMR metabolomics approach, a previous study identified
      unsubstituted B ring flavanones in most species of monocalypts examined, whereas
      these compounds were absent from symphyomyrtles. We hypothesised that
      unsubstituted B ring flavanones act as feeding deterrents for common brushtail
      possums. In the current study, we tested this hypothesis by comparing how much
      possums ate of a basal diet, with diets containing one of four structurally
      related compounds; pinocembrin, flavanone (unsubstituted B ring flavanones),
      chrysin (the flavone analogue of pinocembrin), and naringenin (a flavanone with B
      ring substitution). We found that pinocembrin and flavanone deterred feeding
      relative to the basal diet, but that chrysin and naringenin did not at equivalent
      concentrations. Thus, unsubstituted B-ring flavanones may explain why brushtail
      possums avoid eating monocalypt species. Furthermore, small differences in the
      structure of secondary compounds can have a large impact on antifeedant
      properties. These results demonstrate that metabolomics can be a valuable tool
      for ecologists seeking to understand herbivore feeding preferences. 

PMID- 25994226
TI  - Mycobacterium smegmatis synthesizes in vitro androgens and estrogens from
      different steroid precursors.
AB  - Fast-growing mycobacteria such as Mycobacterium sp. and Mycobacterium smegmatis
      degrade natural sterols. They are a model to study tuberculosis. Interestingly,
      M. smegmatis has been found in river effluents derived from paper production, and
      therefore, it would be important to gain further insight into its capacity to
      synthesize steroids that are potential endocrine disruptors affecting the
      development and reproduction of fishes. To our knowledge, the capacity of M.
      smegmatis to synthesize estrogens and even testosterone has not been previously
      reported. Therefore, the objective of this study was to investigate the capacity
      of M. smegmatis to synthesize in vitro testosterone and estrogens from tritiated
      precursors and to investigate the metabolic pathways involved. Results obtained
      by thin-layer chromatography showed that (3)H-progesterone was transformed to
      17OH-progesterone, androstenedione, testosterone, estrone, and estradiol after 6,
      12, or 24 h of incubation. (3)H-androstenedione was transformed into testosterone
      and estrogens, mainly estrone, and (3)H-testosterone was transformed to estrone
      and androstenedione. Incubation with (3)H-dehydroepiandrosterone rendered
      androstenediol, testosterone, and estrogens. This ability to transform less
      potent sex steroids like androstenedione and estrone into other more active
      steroids like testosterone and estradiol or vice versa suggests that M. smegmatis
      can influence the amount of self-synthesized strong androgens and estrogens and
      can transform those found in the environment. 

PMID- 25994227
TI  - Spectroscopic Evaluation of DNA-Borate Interactions.
AB  - We describe the binding characteristics of two natural borates (colemanite and
      ulexite) to calf thymus DNA by UV-vis absorbance spectroscopy, circular dichroism
      (CD) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and a
      competitive DNA binding assay. Our results suggest that colemanite and ulexite
      interact with calf thymus DNA under a non-intercalative mode of binding and do
      not alter the secondary structure of the DNA helix. The FT-IR spectroscopy
      results indicate that the two borates might interact with DNA through sugar
      phosphate backbone binding. 

PMID- 25994228
TI  - Longitudinal association of C-reactive protein and Haemoglobin A1c over 13 years:
      the European Prospective Investigation into Cancer--Norfolk study.
AB  - BACKGROUND: Type-2 diabetes is associated with systemic inflammation and higher C
      reactive protein (CRP) levels. However, the longitudinal association of CRP and
      haemoglobin-A1c (HbA1c) has not been described in large prospective studies.
      Understanding such associations may shed light on the role of inflammation in
      development of type-2 diabetes and its complications such as cardiovascular
      diseases. METHODS: EPIC-Norfolk is a cohort study of men and women aged 40-79
      years at time of recruitment (1993-1997). Serum CRP (mg/l) was measured using a
      high-sensitivity assay at baseline and 13-years follow-up. HbA1c (%) was measured
      at baseline, 4, and 13 years. Participants were excluded if they were diagnosed
      with diabetes or were taking diabetes medication. Data on at least one
      measurement of CRP and HbA1c was available for 14228 participants (55 % of the
      cohort). RESULTS: In the cross-sectional analysis of baseline data, a 1-SD higher
      loge-CRP (about three-fold higher CRP) was associated with 0.06 (95 % CI 0.04,
      0.08) higher HbA1c (%) adjusted for potential confounders. In longitudinal
      analysis using multivariable linear mixed models, change in CRP over 13 years was
      to a similar extent positively associated with increase in HbA1c, such that 1-SD
      higher longitudinal change in loge-CRP was associated with 0.04 (95 % CI 0.02,
      0.05) increase in HbA1c. CONCLUSION: In this study we found longitudinal
      observational evidence suggesting that increase in systemic inflammation is
      associated with an increase in HbA1c and thus systemic inflammation may have a
      role in development of type-2 diabetes and its complications.

PMID- 25994229
TI  - Tong-xin-luo capsule for patients with coronary heart disease after percutaneous
      coronary intervention.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is a standard treatment for
      coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal
      diameter at six months after PCI, indicates a need for revascularisation.
      Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the
      prophylactic strategies for cardiovascular events in patients after PCI that is
      widely used in China, but its efficacy and safety have not been systematically
      evaluated. OBJECTIVES: To systematically assess the efficacy and safety of Tong
      xin-luo capsules in preventing cardiovascular events after PCI in patients with
      CHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese
      Biomedical Database, Chinese Medical Current Contents, and China National
      Knowledge Infrastructure from their inception to June 2014. We also searched
      other resources, including ongoing trials and research registries. We applied no
      language restrictions. SELECTION CRITERIA: Randomised controlled trials of
      participants with CHD after PCI were included. Participants in the intervention
      group received Tong-xin-luo capsules for at least three months. DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data and assessed the
      risk of bias. Any disagreements were resolved by discussion with a third review
      author. The primary outcomes included occurrence of angiographic restenosis and
      adverse events; the secondary outcomes included myocardial infarction, heart
      failure, angina, all cause mortality, mortality due to any cardiovascular event,
      use of revascularisation, patient acceptability, quality of life and cost
      effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95%
      confidence intervals (CIs). MAIN RESULTS: Sixteen studies involving 1063
      participants were identified. The risk of bias for fifteen studies was high and
      along with imprecision and possible publication bias, this lowered our confidence
      in the results. There was low quality evidence that Tong-xi-luo reduced the rates
      of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction
      (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and
      use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low
      quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38,
      95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any
      cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom
      reported, and included gastrointestinal reactions and nausea. AUTHORS'
      CONCLUSIONS: The addition of Tong-xin-luo to conventional Western medicine may
      possibly prevent restenosis and recurrence of cardiovascular events in patients
      with CHD after PCI. However, the data are limited by publication bias and high
      risk of bias for included studies. Further high-quality trials are required to
      evaluate the potential effects of this intervention.

PMID- 25994231
TI  - A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro.
AB  - A number of metalloenzymes harbor unique cofactors, which are incorporated into
      the apo-enzymes via protein-assisted maturation. In the case of [NiFe]
      hydrogenases, minimally seven maturation factors (HypABCDEF and a specific
      endopeptidase) are involved, making these enzymes an excellent example for
      studying metallocenter assembly in general. Here, we describe an innovative
      toolbox to study maturation involving multiple putative gene products. The two
      core elements of the system are a modular, combinatorial cloning system and a
      cell-free maturation system, which is based on recombinant Escherichia coli
      extracts and/or purified maturases. Taking maturation of the soluble, oxygen
      tolerant [NiFe]-hydrogenase (SH) from Cupriavidus necator as an example, the
      capacities of the toolbox are illustrated. In total 18 genes from C. necator were
      analyzed, including four SH-structural genes, the SH-dedicated hyp-genes and a
      second set of hyp-genes putatively involved in maturation of the Actinobacterium
      like hydrogenase (AH). The two hyp-sets were either expressed in their entirety
      from single vectors or split into functional modules, which enabled flexible
      approaches to investigate limitations, specificities and the capabilities of
      individual constituents to functionally substitute each other. Affinity-tagged
      Hyp-Proteins were used in pull-down experiments to demonstrate direct
      interactions between dedicated or non-related constituents. The dedicated Hyp-set
      from C. necator exhibited the highest maturation efficiency in vitro.
      Constituents of non-related maturation machineries were found to interact with
      and to accomplish partial activation of SH. In contrast to homologues of the Hyp
      family, omission of the SH-specific endopeptidase HoxW completely abolished in
      vitro maturation. We detected stoichiometric imbalances inside the recombinant
      production system, which point to limitations by the cyanylation complex HypEF
      and the premature subunit HoxH. Purification of HoxW revealed strong indications
      for the presence of a putative [4Fe-4S]-cluster, which is unique among this class
      of maturases. Results are discussed in the context of [NiFe]-hydrogenase
      maturation, and in light of the capacity of the novel toolbox.

PMID- 25994230
TI  - Genome-wide small noncoding RNA profiling of pediatric high-grade gliomas reveals
      deregulation of several miRNAs, identifies downregulation of snoRNA cluster HBII
      52 and delineates H3F3A and TP53 mutant-specific miRNAs and snoRNAs.
AB  - Pediatric high-grade gliomas (HGGs) are highly malignant tumors that remain
      incurable and relatively understudied. The crucial role of noncoding RNAs
      (ncRNAs) has been reported in various cancers. However, the study on miRNAs in
      pediatric HGGs is scant and there is no report till date on the status of other
      small ncRNAs. Genome-wide microarray analysis was performed to investigate small
      ncRNA expression in pediatric HGG (n = 14) and compared to adult glioblastoma
      (GBM) signature. The validation of miRNAs and small nucleolar RNAs (snoRNAs) was
      done by real-time polymerase chain reaction. TP53 and H3F3A mutation-specific
      miRNA and snoRNA profiles were generated and analyzed. Pediatric HGGs showed
      upregulation of miR-17/92 and its paralog clusters (miR106b/25 and miR-106a/363),
      whereas majority of downregulated miRNAs belonged to miR379/656 cluster (14q32).
      Unsupervised hierarchical clustering identified two distinct groups.
      Interestingly, Group 2 with downregulated 14q32 cluster showed better overall
      survival. The miRNAs unique to pediatric HGG as compared to adult GBM were
      predicted to affect PDGFR and SMAD2/3 pathways. Similarities were seen between
      pediatric HGG and TP53 mutant miRNA profiles as compared to wild types. Several
      of H3F3A mutation-regulated genes were found to be the targets of H3F3A mutant
      specific miRNAs. Remarkably, a significant downregulation of HBII-52 snoRNA
      cluster was found in pediatric HGGs, and was specific to H3F3A nonmutants. This
      is the first genome-wide profiling study on miRNAs and snoRNAs in pediatric HGGs
      with respect to H3F3A and TP53 mutations. The comparison of miRNA profiles of
      pediatric HGGs and adult GBM reiterates the overlaps and differences as also seen
      with their gene expression and methylation signatures.

PMID- 25994232
TI  - Role of Obesity on the Prognosis of Sudden Sensorineural Hearing Loss in Adults.
AB  - OBJECTIVE: To investigate the role of obesity/overweight on the prognosis of
      sudden sensorineural hearing loss (SSHL). STUDY DESIGN: Retrospective cohort
      study. SETTING: Outpatient department of a community hospital. SUBJECTS AND
      METHODS: We collected 254 adult patients with SSHL from a community hospital. The
      odd ratios of body mass index (BMI) or obesity/overweight (BMI >=25 kg/m(2)) on
      the recovery of SSHL were evaluated with multivariate logistic regression
      analysis. RESULTS: There were 120 (47.2%) patients in the nonobesity group (BMI
      <25 kg/m(2)) and 134 (52.8%) patients in the obesity/overweight group (BMI >=25
      kg/m(2)). The complete and partial recovery rates were 10.0% and 49.2% in the
      nonobesity group and 9.7% and 47.0% in the obesity/overweight group,
      respectively. Univariate logistic regression showed that BMI had no significant
      association with recovery of SSHL (odds ratio [OR] of complete and partial
      recovery versus no recovery = 1.04, 95% confidence interval [CI] = 0.965-1.113, P
      = .327). Multivariate logistic regression analysis also showed that BMI (OR =
      1.04, 95% CI = 0.964-1.131, P = .292) was not significantly associated with the
      recovery of SSHL for all subjects, after adjusting for all considered variables.
      Also, obesity/overweight (BMI >=25 kg/m(2)) had no significant association with
      the recovery of SSHL. CONCLUSION: Obesity/overweight would appear to have no
      significant effect on the prognosis of SSHL.

PMID- 25994233
TI  - An Innovative 3-dimensional Model of the Epitympanum for Teaching of Middle Ear
      Anatomy.
AB  - OBJECTIVE: To facilitate teaching of the anatomy of the epitympanum, we developed
      and evaluated the effectiveness of an interactive 3-dimensional (3D) computer
      model that can be viewed from all angles. STUDY DESIGN: Questionnaire-based
      prospective randomized controlled trial. SETTING: Undergraduate medical education
      program. SUBJECTS AND METHODS: The model was created using Google Sketchup, a 3D
      modeling software. We recruited 72 graduating medical students and randomized
      them into 2 groups. One group was given the 3D model and reading materials on the
      epitympanic anatomy (3D group), while the other group relied on reading material
      and pictures (2-dimensional [2D] group). A questionnaire and anatomy quiz
      assessed the utility of the 3D model in learning the anatomy of the epitympanum.
      RESULTS: The mean age of the participants was 22 years. There were no
      statistically significant differences in demographics and previous experience
      with 3D models. The 3D group was significantly more confident in its ability to
      identify structures of the epitympanum on pictures and computed tomography scans
      when compared to the 2D group. Most participants were in favor of the model as a
      useful learning tool and preferred to use it with an instructor. In the anatomy
      quiz, the 3D group fared significantly better, achieving a mean score of 65.1%
      compared to 32.4% in the 2D group (P < .001). CONCLUSION: The 3D teaching model
      of the epitympanum is efficacious in short-term recall. By allowing the learner
      to visualize relations of the epitympanum from all directions, the model aids in
      appreciation of anatomy and identifications of structures of this region.

PMID- 25994235
TI  - Integration of a semi-rigid proline ligand and 4,4'-bipyridine in the synthesis
      of homochiral metal-organic frameworks with helices.
AB  - A pair of 3-D homochiral metal-organic frameworks (HMOFs) based on a mixed semi
      rigid 5-(2-carboxypyrrolidine-1-carbonyl)isophthalate (PIA) ligand and rigid 4,4'
      bipyridine (bipy), [Co3((R)-PIA)2(bipy)3].6H2O (1-D) and [Co3((S)
      PIA)2(bipy)3].6H2O (1-L) are synthesized and structurally characterized. They are
      enantiomers and exhibit three-dimensional open frameworks. In each structure, the
      PIA ligands link the Co centers into homochiral frameworks with large open
      channels that are occupied by the bipy ligands. Interesting helical chains built
      from the connectivity between PIA ligands and Co centers are presented.
      Antiferromagnetic coupling is observed in 1-D. These results demonstrated that
      the mixed ligand approach is successful for the construction of HMOFs. 

PMID- 25994234
TI  - Cuticular protein with a low complexity sequence becomes cross-linked during
      insect cuticle sclerotization and is required for the adult molt.
AB  - In the insect cuticle, structural proteins (CPs) and the polysaccharide chitin
      are the major components. It has been hypothesized that CPs are cross-linked to
      other CPs and possibly to chitin by quinones or quinone methides produced by the
      laccase2-mediated oxidation of N-acylcatechols. In this study we investigated
      functions of TcCP30, the third most abundant CP in protein extracts of elytra
      (wing covers) from Tribolium castaneum adults. The mature TcCP30 protein has a
      low complexity and highly polar amino acid sequence. TcCP30 is localized with
      chitin in horizontal laminae and vertically oriented columnar structures in rigid
      cuticles, but not in soft and membranous cuticles. Immunoblot analysis revealed
      that TcCP30 undergoes laccase2-mediated cross-linking during cuticle maturation
      in vivo, a process confirmed in vitro using recombinant rTcCP30. We identified
      TcCPR27 and TcCPR18, the two most abundant proteins in the elytra, as putative
      cross-linking partners of TcCP30. RNAi for the TcCP30 gene had no effect on
      larval and pupal growth and development. However, during adult eclosion, ~70% of
      the adults were unable to shed their exuvium and died. These results support the
      hypothesis that TcCP30 plays an integral role as a cross-linked structural
      protein in the formation of lightweight rigid cuticle of the beetle. 

PMID- 25994236
TI  - JAM-A promotes wound healing by enhancing both homing and secretory activities of
      mesenchymal stem cells.
AB  - The homing ability and secretory function of mesenchymal stem cells (MSCs) are
      key factors that influence cell involvement in wound repair. These factors are
      controlled by multilayer regulatory circuitry, including adhesion molecules, core
      transcription factors (TFs) and certain other regulators. However, the role of
      adhesion molecules in this regulatory circuitry and their underlying mechanism
      remain undefined. In the present paper, we demonstrate that an adhesion molecule,
      junction adhesion molecule A (JAM-A), may function as a key promoter molecule to
      regulate skin wound healing by MSCs. In in vivo experiments, we show that JAM-A
      up-regulation promoted both MSC homing to full-thickness skin wounds and wound
      healing-related cytokine secretion by MSCs. In vitro experiments also showed that
      JAM-A promoted MSC proliferation and migration by activating T-cell lymphoma
      invasion and metastasis 1 (Tiam1). We suggest that JAM-A up-regulation can
      increase the proliferation, cytokine secretion and wound-homing ability of MSCs,
      thus accelerating the repair rate of full-thickness skin defects. These results
      may provide insights into a novel and potentially effective approach to improve
      the efficacy of MSC treatment. 

PMID- 25994237
TI  - The mediated effects of maternal depression and infant temperament on maternal
      role.
AB  - We examined prenatal depression, postpartum depression, and infant temperament,
      respectively, in a mediated process model to predict maternal role. Using a
      prospective, observational design, we surveyed 168 women during pregnancy and
      then in postpartum. Data analyses supported the contribution of each variable in
      an ascending fashion (ab = -0.01, SE = 0.004, 95 % CI [-0.021, -0.004]), such
      that infant temperament had the strongest effects (sr(2) = .124, p < .001).
      Further, postpartum depression was found to influence maternal role with both
      direct effects and indirect effects via infant temperament. These results
      highlighted the significant impact postpartum depression may have on maternal
      role. Future interventions targeting mothers experiencing or who are at risk for
      depression may consider tools to improve mother-baby interactions. The effects of
      such intervention may subsequently improve both infant temperament and maternal
      role evaluation.

PMID- 25994238
TI  - MoS2 Surface Structure Tailoring via Carbonaceous Promoter.
AB  - Atomically thin semiconducting transition-metal dichalcogenides have been
      attracting lots of attentions, particularly, molybdenum disulfide (MoS2)
      monolayers show promising applications in field effect transistors,
      optoelectronics and valleytronics. However, the controlled synthesis of highly
      crystalline MoS2 remain a challenge especially the systematic approach to
      manipulate its structure and morphology. Herein, we report a method for
      controlled synthesis of highly crystalline MoS2 by using chemical vapor
      deposition method with carbonaceous materials as growth promoter. A uniform and
      highly crystalline MoS2 monolayer with the grain size close to 40 MUm was
      achieved. Furthermore, we extend the method to the manipulation of MoS2
      morphology, flower-shape vertical grown MoS2 layers were obtained on growth
      promoting substrates. This simple approach allows an easy access of highly
      crystalline MoS2 layers with morphology tuned in a controllable manner. Moreover,
      the flower-shape MoS2 grown on graphene oxide film used as an anode material for
      lithium-ion batteries showed excellent electrochemical performance.

PMID- 25994239
TI  - Short-term reproducibility and variability of the pupillographic sleepiness test.
AB  - OBJECTIVES: The pupillographic sleepiness test (PST) measures the amplitude of
      the fluctuations of pupil size in the dark, which reflects the level of central
      nervous system activation and thus alertness. The aim of this study was to assess
      the short-term reproducibility and variability of the results obtained with the
      PST in normal healthy subjects. METHODS: The PST was measured at 9.00, 11:00, and
      13:00 h on three consecutive days in 13 young adults. Subjective sleepiness was
      assessed with the Stanford Sleepiness Scale (SSS) and with a Visual Analogue
      Scale (VAS). The intra-class correlation (ICC), a measure of reproducibility and
      the intra- and inter-individual variability, was calculated. RESULTS: ANOVA
      analysis of the data revealed no significant differences in the PST measurements
      for testing day. Time of day and subject did however significantly affect the
      results with an ICC 73.1%. For the SSS and VAS, the ICC was 38.8% and 45.9%,
      respectively. The intra- and inter-individual variability in PST results did not
      differ considerably between time and days. CONCLUSIONS: We conclude that
      recordings of the PST have a good reproducibility and low intra- and inter
      individual variability compared to subjective scales of sleepiness or the
      Multiple Sleep Latency Test. The PST is thus a viable method to measure daytime
      sleepiness objectively.

PMID- 25994240
TI  - Nearly 3,000 salivary stones: some clinical and epidemiologic aspects.
AB  - OBJECTIVES/HYPOTHESIS: To investigate epidemiological features and symptoms of
      sialolithiasis and their implications for diagnosis and management. STUDY DESIGN:
      Retrospective cohort study. METHODS: Retrospective analysis on 2,322 patients
      with sialolithiasis, between 1987 and 2009. The statistical significance between
      two sample distributions was computed using analysis of variance Student t test
      for two-tailed distribution. RESULTS: A total of 2,959 calculi were identified by
      means of ultrasound. Of those, 80.4% were located in the submandibular duct
      system (53% hilar/proximal, 37% distal, 10% intraparenchymal) and 19.6% were
      parotid stones (83% in Stensen's duct, 17% intraparenchymal). Sialoliths had been
      discovered beforehand in the submandibular gland (P = 0.00024; t test). Symptoms,
      measured from first visit, lasted on average 26 months (range: 1 day-30 years).
      The main group suffered from swelling (50.3%), followed by painful swelling
      (41.6%) and pain (3.1%). Multiple stones were found in 16.9% of patients (18.1%
      in the submandibular gland; 14.3% in the parotid). Average stone diameter in the
      submandibular gland was 8.3 mm (range 1-35 mm), and the stones were in Lustmann
      group II (46%). In the parotid gland, the average diameter was 6.4 mm (range 1-31
      mm), and 51% were in Lustmann group I. CONCLUSION: Nowadays, epidemiologic
      features and clinical manifestations of sialolithiasis play an important role,
      assisting not only in diagnosis but also in determining appropriate treatment.
      Due to their location and smaller diameter, parotid stones in some cases can only
      be treated using a mini-invasive endoscopic technique. Submandibular stones more
      often require a combined approach. LEVEL OF EVIDENCE: 4

PMID- 25994241
TI  - Alendronate-decorated biodegradable polymeric micelles for potential bone
      targeted delivery of vancomycin.
AB  - Osteomyelitis is a bone infection disease which is caused by bacteria or other
      germs, and could cause serious impact on the health and working capacity of the
      patients. Alendronate (ALN) can chelate strongly with the calcium ion of
      hydroxyapatite (HA) which is commonly used to treat osteoporosis. Nanomedicine
      has attracted a lot of attention in that the nano-sized carrier can deliver drug
      molecules to specific site of interest with the aid of targeting moiety and
      achieve sustained release, resulting in improved therapeutic effect and reduced
      side effect. In this study, micelles self-assembled from poly(lactic acid-co
      glycolic acid)-block-poly(ethylene glycol)-alendronate (PLGA-PEG-ALN) copolymer
      were prepared for bone-targeted delivery of vancomycin (Van). The chemical
      structure of PLGA-PEG-ALN was confirmed by proton nuclear magnetic resonance
      ((1)H-NMR) spectroscopy. The formation of the nanoparticles was characterized by
      dynamic light scattering, transmission electronic microscopy as well as the
      critical micelle concentration measurement. Release profiles from the micelles
      revealed that the conjugation of ALN to the surface of micelle did not pose
      adverse effect on the drug-loading capacity and release behaviors. The
      cytotoxicity of Van-loaded PLGA-PEG-ALN micelles as well as the blank micelles
      was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay toward rat bone marrow stromal cells (rBMSCs) and human embryonic
      hepatocytes (L02 cells), and results showed that this Van-loaded micelle
      possesses appropriate cytotoxicity and is safe in the potential treatment of
      osteomyelitis. The in vitro affinity of PLGA-PEG-ALN micelles to the HA was also
      confirmed in vitro. The antibacterial effect of Van-loaded PLGA-PEG-ALN micelles
      was tested against Staphylococcus aureus (SA) which is the main pathogenic
      bacteria in osteomyelitis, and the results showed that the Van-loaded micelles
      can effectively inhibit the growth of SA. These results demonstrated that the
      PLGA-PEG-ALN micelles may be potentially used for the bone targeted delivery of
      Van. 

PMID- 25994243
TI  - L-Tryptophan on Cu(111): engineering a molecular labyrinth driven by indole
      groups.
AB  - The present article investigates the adsorption and molecular orientation of L
      Tryptophan, which is both an essential amino acid important for protein synthesis
      and of particular interest for the development of chiral molecular electronics
      and biocompatible processes and devices, on Cu(111) using scanning tunneling
      microscopy and spectroscopy at 55 K and at room temperature. The arrangement of
      chemisorbed L-Tryptophan on the copper surface varies with both temperature and
      surface coverage. At low coverage, small clusters form on the surface
      irrespective of temperature, while at high coverage an ordered chain structure
      emerges at room temperature, and a tightly packed structure forms a molecular
      labyrinth at low temperature. The dominating superstructure of the adsorbates
      arises from intermolecular hydrogen bonding, and pi-bonding interactions between
      the indole groups of neighboring molecules and the Cu surface. 

PMID- 25994242
TI  - Comparison of the global gene expression profiles in the bovine endometrium
      between summer and autumn.
AB  - Heat stress compromises fertility during summer in dairy and beef cows by causing
      nutritional, physiological and reproductive damages. To examine the difference in
      endometrial conditions in cows between summer and autumn, gene expression
      profiles were compared using a 15 K bovine oligo DNA microarray. The trial was
      conducted in the summer (early in September) and autumn (mid-November) seasons of
      two consecutive years (2013-2014) in Morioka, Japan. Endometrial samples were
      collected from the cows using a biopsy technique. The expressions of 268 genes
      were significantly higher in the endometrium collected in summer than those
      collected in autumn, whereas the expressions of 369 genes were lower (P<0.05 or
      lower). Messenger RNA expressions of glycoprotein 2 (GP2), neurotensin (NTS),E
      cadherin (CDH1) and heat shock 105kDa/110kDa protein 1 (HSPH1) were validated by
      quantitative real-time PCR. Transcripts of GP2 and NTS were more abundant in the
      endometrium from summer than in the endometrium from autumn (P < 0.05). In
      contrast, the mRNA expressions of CDH1 were lower (P < 0.05) and those of HSPH1
      tended to be low (P = 0.09) in the endometrium from summer. Immunohistochemical
      staining showed that GP2, NTS and HSPH1 were expressed in the endometrial
      epithelial or glandular epithelial cells. The serum concentrations of NTS
      collected from the cows in summer were higher than those collected from cows in
      autumn (P < 0.05). Collectively, the different gene expression profiles may
      contribute to functional differences in the endometrium between summer and
      autumn, and the increases in GP2 and NTS may have a relationship with the
      endometrial deficiency that causes infertility of cows in summer. 

PMID- 25994244
TI  - Berardinelli-Seip syndrome and achalasia: a shared pathomechanism?
AB  - Berardinelli-Seip congenital lipodystrophy (BSCL) is an uncommon autosomal
      recessive disorder. Patients with BSCL present with a distinct phenotype since
      subcutaneous fat is largely lacking and musculature has become more prominent.
      During childhood, diabetes and acanthosis nigricans evolve and female patients
      may develop hirsutism. Different genes encoding this entity have been described.
      Achalasia is a rare esophageal motility disorder, characterized by its distinct
      motility pattern with absent or incomplete lower esophageal sphincter (LES)
      relaxations. The exact cause of achalasia is yet unknown. Here, we describe a
      patient with achalasia in the context of BSCL, which might be linked by a shared
      pathophysiologic background, as evaluated in this case report. CONCLUSION: In a
      BSCL patient presenting with gastrointestinal symptoms, a motility disorder of
      the gastrointestinal tract should be considered. WHAT IS KNOWN: * Berardinelli
      Seip congenital lipodystrophy (BSCL) and achalasia are both disorders
      characterized by low prevalence. What is New: * Co-existence of both diseases is
      described in this report. Linkage by a potential common pathophysiologic
      background is discussed in this paper.

PMID- 25994246
TI  - Krakow's children cohort and long-term follow-up of thimerosal exposure--design
      and statistics.

PMID- 25994245
TI  - Comparison of Coopdech(r), CoPilot(r), Intubrite(r), and Macintosh laryngoscopes
      for tracheal intubation during pediatric cardiopulmonary resuscitation: a
      randomized, controlled crossover simulation trial.
AB  - The aim of the study was to compare the intubation times and success rates of
      various laryngoscopes during resuscitation in pediatric emergency intubation with
      uninterrupted chest compression on a standardized pediatric manikin model. This
      was a randomized crossover study with 107 paramedic participants. We compared
      times to successful intubation, intubation success rates, and glottic visibility
      using a Cormack-Lehane grade for Macintosh, Intubrite(r), Coopdech(r), and
      Copilot(r) laryngoscopes. One hundred seven paramedics (mean age 31.2 +/- 7.5
      years) routinely involved in the management of prehospital care participated in
      this study. Intubation success rates (overall effectiveness), which was the
      primary study endpoint, were highest for the Coopdech(r) and CoPilot(r) devices
      (100 %) and were lowest for Intubrite(r) (89.7 %, p < 0.001) and Macintosh (80.4
      %, p < 0.001). The secondary study endpoint, time to first effective ventilation,
      was achieved fastest when using the Coopdech(r) laryngoscope (21.6 +/- 6.2 s) and
      was significantly slower with all other devices (Intubrite(r) 25.4 +/- 10.5 s, p
      = 0.006; CoPilot(r) 25.6 +/- 7.4 s, p = 0.007; Macintosh 29.4 +/- 8.2 s, p <
      0.001). CONCLUSION: We conclude that in child simulations managed by paramedics,
      the Coopdech(r) and Copilot(r) video laryngoscopes performed better than the
      standard Macintosh or Intubrite(r) laryngoscopes for endotracheal intubation
      during child chest compression.

PMID- 25994247
TI  - Risk of oral and gastrointestinal mucosal injury in patients with solid tumors
      treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic
      review and meta-analysis.
AB  - BACKGROUND: The authors performed a systematic review and meta-analysis of
      diarrhea and stomatitis associated with the use of everolimus, temsirolimus or
      ridaforolimus in patients with solid tumors. PATIENTS AND METHODS: Eligible
      studies included randomized trials of patients with solid tumors on everolimus,
      temsirolimus or ridaforolimus, describing the events of diarrhea and stomatitis.
      RESULTS: After exclusion of ineligible studies, a total of 18 clinical trials
      including 8143 patients were considered eligible for the meta-analysis. The
      relative risk ratios of all-grade diarrhea and stomatitis were 1.94 (95% CI: 1.6
      2.36; p < 0.00001) and 3.54 (95% CI: 2.59-4.84; p < 0.00001), respectively, while
      the relative risk ratios of high-grade diarrhea and stomatitis were 3.49 (95% CI:
      2.39-5.09; p < 0.00001) and 6.98 (95% CI: 4.76-10.26; p < 0.00001), respectively.
      On subgroup analysis, there was no statistically significant difference between
      everolimus and temsirolimus in the risk of relevant adverse events. CONCLUSIONS:
      This meta-analysis demonstrated that regimens containing everolimus, temsirolimus
      or ridaforolimus for the treatment of solid tumors are associated with a
      significantly increased risk of all-grade and high-grade diarrhea and stomatitis.
      Close clinical monitoring is required when administering these drugs.

PMID- 25994248
TI  - Tunable Luminescent Carbon Nanospheres with Well-Defined Nanoscale Chemistry for
      Synchronized Imaging and Therapy.
AB  - In this work, we demonstrate the significance of defined surface chemistry in
      synthesizing luminescent carbon nanomaterials (LCN) with the capability to
      perform dual functions (i.e., diagnostic imaging and therapy). The surface
      chemistry of LCN has been tailored to achieve two different varieties: one that
      has a thermoresponsive polymer and aids in the controlled delivery of drugs, and
      the other that has fluorescence emission both in the visible and near-infrared
      (NIR) region and can be explored for advanced diagnostic modes. Although these
      particles are synthesized using simple, yet scalable hydrothermal methods, they
      exhibit remarkable stability, photoluminescence and biocompatibility. The
      photoluminescence properties of these materials are tunable through careful
      choice of surface-passivating agents and can be exploited for both visible and
      NIR imaging. Here the synthetic strategy demonstrates the possibility to
      incorporate a potent antimetastatic agent for inhibiting melanomas in vitro.
      Since both particles are Raman active, their dispersion on skin surface is
      reported with Raman imaging and utilizing photoluminescence, their depth
      penetration is analysed using fluorescence 3D imaging. Our results indicate a new
      generation of tunable carbon-based probes for diagnosis, therapy or both. 

PMID- 25994249
TI  - D-dimer for prediction of long-term outcome in cryptogenic stroke patients with
      patent foramen ovale.
AB  - Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the
      possibility of paradoxical embolism from venous to systemic circulation. D-dimer
      level is used to screen venous thrombosis. We investigated the risk of embolism
      and mortality according to the presence of PFO and D-dimer levels in cryptogenic
      stroke patients. A total of 570 first-ever cryptogenic stroke patients who
      underwent transesophageal echocardiography were included in this study. D-dimer
      was assessed using latex agglutination assay during admission. The association of
      long-term outcomes with the presence of PFO and D-dimer levels was investigated.
      PFO was detected in 241 patients (42.3 %). During a mean 34.0 +/- 22.8 months of
      follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in
      33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox
      regression analysis showed that a D-dimer level of > 1,000 ng/ml was an
      independent predictor for recurrent ischaemic stroke in patients with PFO (hazard
      ratio 5.341, 95 % confidence interval 1.648-17.309, p=0.005), but not in those
      without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml
      was independently related with all-cause mortality. The risk of pulmonary
      thromboembolism tended to be high in patients with high D-dimer levels,
      regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive
      of the long-term outcome, which differed according to the presence of PFO. The
      coexistence of PFO and a high D-dimer level increased the risk of recurrent
      ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful
      for predicting outcomes and deciding treatment strategy. 

PMID- 25994250
TI  - Tautomeric transition between wobble A.C DNA base mispair and Watson-Crick-like
      A.C* mismatch: microstructural mechanism and biological significance.
AB  - Here, we use MP2/DFT quantum-chemical methods combined with Quantum Theory of
      Atoms in Molecules to study the tautomeric transition between wobble A.C(w)
      mismatch and Watson-Crick-like A.C*(WC) base mispair, proceeding non
      dissociatively via sequential proton transfer between bases through the planar,
      highly stable and zwitterionic TS(A?C-)(A?C(W)<-->A?C&(WC)) transition state
      joined by the participation of (A)N6(+)H???N4(-)(C), (A)N1(+)H???N4(-)(C) and
      (A)C2(+)H???N3(-)(C) H-bonds. Notably, the A.C(w) <-> A.C*(WC) tautomerization
      reaction is accompanied by 10 unique patterns of the specific intermolecular
      interactions that consistently replace each other. Our data suggest that
      biologically significant A.C(w) -> A.C*(WC) tautomerization is a kinetically
      controlled pathway for formation of the enzymatically competent Watson-Crick-like
      A.C*(WC) DNA base mispair in the essentially hydrophobic recognition pocket of
      the high-fidelity DNA-polymerase, responsible for the occurrence of spontaneous
      point AC/CA incorporation errors during DNA biosynthesis.

PMID- 25994251
TI  - Nanoscale Piezoelectric Properties of Self-Assembled Fmoc-FF Peptide Fibrous
      Networks.
AB  - Fibrous peptide networks, such as the structural framework of self-assembled
      fluorenylmethyloxycarbonyl diphenylalanine (Fmoc-FF) nanofibrils, have mechanical
      properties that could successfully mimic natural tissues, making them promising
      materials for tissue engineering scaffolds. These nanomaterials have been
      determined to exhibit shear piezoelectricity using piezoresponse force
      microscopy, as previously reported for FF nanotubes. Structural analyses of Fmoc
      FF nanofibrils suggest that the observed piezoelectric response may result from
      the noncentrosymmetric nature of an underlying beta-sheet topology. The observed
      piezoelectricity of Fmoc-FF fibrous networks is advantageous for a range of
      biomedical applications where electrical or mechanical stimuli are required. 

PMID- 25994252
TI  - Investigating Moorella thermoacetica metabolism with a genome-scale constraint
      based metabolic model.
AB  - Moorella thermoacetica is a strictly anaerobic, endospore-forming, and
      metabolically versatile acetogenic bacterium capable of conserving energy by both
      autotrophic (acetogenesis) and heterotrophic (homoacetogenesis) modes of
      metabolism. Its metabolic diversity and the ability to efficiently convert a wide
      range of compounds, including syngas (CO + H2) into acetyl-CoA have made this
      thermophilic bacterium a promising host for industrial biotechnology
      applications. However, lack of detailed information on M. thermoacetica's
      metabolism is a major impediment to its use as a microbial cell factory. In order
      to overcome this issue, a genome-scale constraint-based metabolic model of
      Moorella thermoacetica, iAI558, has been developed using its genome sequence and
      physiological data from published literature. The reconstructed metabolic network
      of M. thermoacetica comprises 558 metabolic genes, 705 biochemical reactions, and
      698 metabolites. Of the total 705 model reactions, 680 are gene-associated while
      the rest are non-gene associated reactions. The model, in addition to simulating
      both autotrophic and heterotrophic growth of M. thermoacetica, revealed
      degeneracy in its TCA-cycle, a common characteristic of anaerobic metabolism.
      Furthermore, the model helped elucidate the poorly understood energy conservation
      mechanism of M. thermoacetica during autotrophy. Thus, in addition to generating
      experimentally testable hypotheses regarding its physiology, such a detailed
      model will facilitate rapid strain designing and metabolic engineering of M.
      thermoacetica for industrial applications. 

PMID- 25994253
TI  - A high-fat diet impairs learning that is dependent on the dorsal hippocampus but
      spares other forms of learning.
AB  - Two experiments were conducted to evaluate the effects of a high-fat diet (HFD)
      on two tasks that were either dependent on the dorsal hippocampus (DH) or
      independent of the DH. A total of 80 adult male Sprague Dawley rats were
      administered either a lard-based HFD (60% of calories from fat) or a control diet
      (10% of calories from fat) for 8 weeks, and then were trained and tested on
      either the latent cue preference (LCP) task or the conditioned cue preference
      (CCP) task in a 3-compartment box apparatus (2 end-compartments and 1 middle
      compartment). The end compartments of the box apparatus contained either a single
      environmental cue (DH-independent) or multiple environmental cues (DH-dependent).
      During training trials for the LCP and CCP tasks, on alternating days, rats were
      given access to water in 1 of the 2 end compartments and no water in the opposite
      end compartment. Rats were water-replete during LCP training and were water
      deprived during CCP training. During testing for both tasks, all rats were water
      deprived and given free access to all compartments while the amounts of time
      spent in each compartment were recorded. Results showed that rats given the HFD
      demonstrated no compartment preferences during both LCP and CCP testing when the
      compartments contained multiple cues, while rats fed the control diet
      demonstrated normal compartment preference behavior. However, when the
      compartments contained a single environmental cue, rats given either the HFD and
      control diet demonstrated normal LCP and CCP learning. These results demonstrate
      that consumption of a HFD disrupted both LCP and CCP learning in a multiple-cue
      (DH-dependent) environment, but did not impair either type of learning in a
      single-cue (DH-independent) environment. This may be due to selective impairment
      of the DH caused by increased oxidative stress, inflammation, and/or disrupted
      neurotransmission produced by consumption of the HFD.

PMID- 25994254
TI  - Development of a regulatable plasmid-based gene expression system for Clostridium
      thermocellum.
AB  - Clostridium thermocellum can rapidly solubilize cellulose and produces ethanol as
      an end product of its metabolism. As such, it is a candidate for bioethanol
      production from plant matter. In this study, we developed an inducible expression
      system for C. thermocellum based on its native celC operon. We enhanced
      expression over the native operon structure by placing the repressor gene, glyR3,
      immediately after the celC promoter, and expressing the target gene after glyR3.
      Upon the addition of the inducer substrate, laminaribiose, an approximately 40
      fold increase in gene expression was obtained using the test gene spo0A.
      Furthermore, induction of the sporulation histidine kinase, clo1313_1942,
      increased sporulation frequency by approximately 10,000-fold relative to an
      uninduced control. We have also shown that the laminaribiose (beta1-3-linked
      carbon source) utilization pathway is not catabolite repressed by cellobiose, a
      beta1-4-linked carbon source frequently used for C. thermocellum cultivation in
      laboratory conditions. Selective expression of target genes has the potential to
      inform metabolic engineering strategies as well as increase fundamental
      understanding of C. thermocellum biology. 

PMID- 25994256
TI  - Rapid detection of Yersinia pestis recombinant fraction 1 capsular antigen.
AB  - Yersinia pestis, an infectious bacterium that is a causative agent of plague, a
      disease which has been shown to be one of the most feared in history and which
      has caused millions of deaths. The capsule-like fraction 1 (F1) antigen expressed
      by Y. pestis is a known specific marker for the identification of the bacteria;
      therefore, the detection of F1 is important for Y. pestis recognition. In this
      study, a rapid, sensitive, and specific technique, the lateral flow assay (LFA),
      was successfully developed to detect Y. pestis by the recombinant F1 antigen. The
      assay that utilized an anti-F1 polyclonal antibody (Pab) to identify the bacteria
      was based on a double-antibody sandwich format on a nitrocellulose membrane. With
      the LFA method, 50 ng/ml of recombinant F1 protein and 10(5) CFU/mL of Y. pestis
      could be detected in less than 10 min. This assay also showed no cross-reaction
      with other Yersinia spp. or with some selected capsule-producing
      Enterobacteriaceae strains. Furthermore, detection of Y. pestis in simulated
      samples has been evaluated. The detection sensitivity of Y. pestis in various
      matrices was 10(5) CFU/mL, which was identical to that in PBS buffer. The results
      obtained suggest that LFA is an excellent tool for detection of Y. pestis
      contamination in an environment and hence can be used to monitor plague diseases
      when they emerge. 

PMID- 25994255
TI  - Production of canine adenovirus type 2 in serum-free suspension cultures of MDCK
      cells.
AB  - The potential of adherent Madin Darby Canine Kidney (MDCK) cells for the
      production of influenza viruses and canine adenovirus type 2 (CAV-2) for vaccines
      or gene therapy approaches has been shown. Recently, a new MDCK cell line
      (MDCK.SUS2) that was able to grow in suspension in a fully defined system was
      established. In this work, we investigated whether the new MDCK.SUS2 suspension
      cell line is suitable for the amplification of CAV-2 under serum-free culture
      conditions. Cell growth performance and CAV-2 production were evaluated in three
      serum-free media: AEM, SMIF8, and EXCELL MDCK. CAV-2 production in shake flasks
      was maximal when AEM medium was used, resulting in an amplification ratio of
      infectious particles (IP) of 142 IP out/IP in and volumetric and cell-specific
      productivities of 2.1 * 10(8) IP/mL and 482 IP/cell, respectively. CAV-2
      production was further improved when cells were cultivated in a 0.5-L stirred
      tank bioreactor. To monitor infection and virus production, cells were analyzed
      by flow cytometry. A correlation between the side scatter measurement and CAV-2
      productivity was found, which represents a key feature to determine the best
      harvesting time during process development of gene therapy vectors that do not
      express reporter genes. This work demonstrates that MDCK.SUS2 is a suitable cell
      substrate for CAV-2 production, constituting a step forward in developing a
      production process transferable to industrial scales. This could allow for the
      production of high CAV-2 titers either for vaccination or for gene therapy
      purposes.

PMID- 25994257
TI  - The effect of tryptophol on the bacteriophage infection in high-temperature
      environment.
AB  - Small metabolites can participate in the virus-host interactions in eukaryotes.
      However, little is known about roles of metabolites in the interactions between
      bacteria and bacteriophages. In this study, the metabolomic profilings of
      bacteriophage GVE2-infected and virus-free Geobacillus sp. E263, a thermophilic
      bacterium isolated from a deep-sea hydrothermal vent, were characterized. The
      results showed that metabolites tryptophol, adenine, and hydroxybenzylalcohol
      were significantly elevated in Geobacillus sp. E263 in response to the GVE2
      infection. Furthermore, our data indicated that tryptophol was involved in the
      bacteriophage infection. Tryptophol could inhibit the infection/replication of
      GVE2 by interacting with the host's Clp protease. Therefore, our study revealed
      novel aspects of metabolites during the bacteriophage infection in high
      temperature environment.

PMID- 25994258
TI  - Erratum to: Identification of two novel rabbit hemorrhagic disease virus (RHDV) B
      cell epitopes and evaluation of its immunoprotection against RHDV.

PMID- 25994259
TI  - Effect of temperature on removal of antibiotic resistance genes by anaerobic
      digestion of activated sludge revealed by metagenomic approach.
AB  - As antibiotic resistance continues to spread globally, there is growing interest
      in the potential to limit the spread of antibiotic resistance genes (ARGs) from
      wastewater sources. In particular, operational conditions during sludge digestion
      may serve to discourage selection of resistant bacteria, reduce horizontal
      transfer of ARGs, and aid in hydrolysis of DNA. This study applied metagenomic
      analysis to examine the removal efficiency of ARGs through thermophilic and
      mesophilic anaerobic digestion using bench-scale reactors. Although the relative
      abundance of various ARGs shifted from influent to effluent sludge, there was no
      measureable change in the abundance of total ARGs or their diversity in either
      the thermophilic or mesophilic treatment. Among the 35 major ARG subtypes
      detected in feed sludge, substantial reductions (removal efficiency >90%) of 8
      and 13 ARGs were achieved by thermophilic and mesophilic digestion, respectively.
      However, resistance genes of aadA, macB, and sul1 were enriched during the
      thermophilic anaerobic digestion, while resistance genes of erythromycin esterase
      type I, sul1, and tetM were enriched during the mesophilic anaerobic digestion.
      Efflux pump remained to be the major antibiotic resistance mechanism in sludge
      samples, but the portion of ARGs encoding resistance via target modification
      increased in the anaerobically digested sludge relative to the feed. Metagenomic
      analysis provided insight into the potential for anaerobic digestion to mitigate
      a broad array of ARGs.

PMID- 25994260
TI  - Beyond function: Using assistive technologies following lower limb loss.
AB  - OBJECTIVE: To explore how individuals experience and perceive the use of
      assistive technologies following lower limb loss. DESIGN: Cross-sectional
      qualitative interview design. PATIENTS: Thirty individuals with lower limb
      amputation were recruited from a multi-disciplinary rehabilitation programme (26
      males and 4 females); comprising individuals with above-knee (n=16), below-knee
      (n=12) and bilateral (n=2) amputations. Patients were at least 15 months post
      rehabilitation, at least 18 years old and spoke English. METHODS: Semi-structured
      interviews were conducted via telephone or in person. Interview data were
      inductively thematically analysed by a researcher who had no previous contact
      with participants. RESULTS: Three key themes were identified: "It didn't feel
      part of me" - Heightened awareness and experiences of distance from prostheses
      following lower limb loss; "Depending on others is really tough" - Independence
      through assistive technologies; and "I feel confident with this leg" - The value
      of prosthesis use following amputation. CONCLUSION: The findings demonstrate that
      individuals with lower limb loss perceive and experience assistive technologies
      to have uses in ways beyond their potential for functional restoration. They may
      also attribute meanings and values relating to such technologies that may
      influence their use. Ascertaining and being aware of individuals' experiences and
      perceptions of assistive technologies is important for lower limb loss
      rehabilitation.

PMID- 25994261
TI  - Biodegradation of diesel oil by a novel microbial consortium: comparison between
      co-inoculation with biosurfactant-producing strain and exogenously added
      biosurfactants.
AB  - Bioremediation, involving the use of microorganisms to detoxify or remove
      pollutants, is the most interesting strategy for hydrocarbon remediation. In this
      aim, four hydrocarbon-degrading bacteria were isolated from oil-contaminated soil
      in Tunisia. They were identified by the 16S rDNA sequence analysis, as
      Lysinibacillus bronitolerans RI18 (KF964487), Bacillus thuringiensis RI16
      (KM111604), Bacillus weihenstephanensis RI12 (KM094930), and Acinetobacter
      radioresistens RI7 (KJ829530). Moreover, a lipopeptide biosurfactant produced by
      Bacillus subtilis SPB1, confirmed to increase diesel solubility, was tested to
      increase diesel biodegradation along with co-inoculation with two biosurfactant
      producing strains. Culture studies revealed the enhancement of diesel
      biodegradation by the selected consortium with the addition of SPB1 lipopeptide
      and in the cases of co-inoculation by biosurfactant-producing strain. In fact, an
      improvement of about 38.42 and 49.65 % of diesel degradation was registered in
      the presence of 0.1 % lipopeptide biosurfactant and when culturing B. subtilis
      SPB1 strain with the isolated consortium, respectively. Furthermore, the best
      improvement, evaluated to about 55.4 %, was recorded when using the consortium
      cultured with B. subtilis SPB1 and A. radioresistens RI7 strains. Gas
      chromatography analyses were correlated with the gravimetric evaluation of the
      residual hydrocarbons. Results suggested the potential applicability of the
      selected consortium along with the ex situ- and in situ-added biosurfactant for
      the effective bioremediation of diesel-contaminated water and soil.

PMID- 25994262
TI  - Effects of urbanization on gaseous and particulate polycyclic aromatic
      hydrocarbons and polychlorinated biphenyls in a coastal city, China: levels,
      sources, and health risks.
AB  - Gas/particle distributions of polycyclic aromatic hydrocarbons (PAHs) and
      polychlorinated biphenyls (PCBs) were measured in Xiamen from May 2009 to March
      2010 to evaluate the impacts of urbanization on the fate of persistent organic
      pollutants (POPs) in the atmospheric environment. In a newly developing area
      (NDA), the concentrations of 16 PAHs (gas + particle) were significantly higher
      than that a historically urbanized area (HUA) (p value <0.05), while the trend of
      28 PCBs was reversed. Diagnostic ratios and principle component analysis (PCA)
      implied that atmospheric PAHs in the NDA were mainly derived from petrogenic
      combustion, including mixed sources of vehicle emissions, biomass burning and oil
      combustion, while pyrogenic combustion (e.g., traffic and coal combustion) was
      considered the major source of PAHs in the HUA. Atmospheric PCBs in both HUA and
      NDA were dominated by TriCBs and PeCBs related to the use of commercial mixtures
      (Aroclors 1242 and 1254). Based on the toxicological equivalent factor (TEF)
      approach, total benzo[a]pyrene equivalent values in the HUA and NDA were 1.12 and
      2.02 ng m(-3), respectively, exceeding the standard threshold values (1.0 ng m(
      3)) of China and WHO. Average daily intake of dioxin-like compounds was 0.2 pg
      kg(-1) day(-1) in the HUA, which are below the WHO tolerable daily intake level.
      The results showed that the contribution to the toxic equivalency (TEQ) was
      dominated by PCB169, PCB105, and PCB81.

PMID- 25994263
TI  - Effects of sampling methods on the quantity and quality of dissolved organic
      matter in sediment pore waters as revealed by absorption and fluorescence
      spectroscopy.
AB  - Despite literature evidence suggesting the importance of sampling methods on the
      properties of sediment pore waters, their effects on the dissolved organic matter
      (PW-DOM) have been unexplored to date. Here, we compared the effects of two
      commonly used sampling methods (i.e., centrifuge and Rhizon sampler) on the
      characteristics of PW-DOM for the first time. The bulk dissolved organic carbon
      (DOC), ultraviolet-visible (UV-Vis) absorption, and excitation-emission matrixes
      coupled with parallel factor analysis (EEM-PARAFAC) of the PW-DOM samples were
      compared for the two sampling methods with the sediments from minimal to severely
      contaminated sites. The centrifuged samples were found to have higher average
      values of DOC, UV absorption, and protein-like EEM-PARAFAC components. The
      samples collected with the Rhizon sampler, however, exhibited generally more
      humified characteristics than the centrifuged ones, implying a preferential
      collection of PW-DOM with respect to the sampling methods. Furthermore, the
      differences between the two sampling methods seem more pronounced in relatively
      more polluted sites. Our observations were possibly explained by either the
      filtration effect resulting from the smaller pore size of the Rhizon sampler or
      the desorption of DOM molecules loosely bound to minerals during centrifugation,
      or both. Our study suggests that consistent use of one sampling method is crucial
      for PW-DOM studies and also that caution should be taken in the comparison of
      data collected with different sampling methods.

PMID- 25994265
TI  - Time-dependent expression and activity of cytochrome P450 1s in early life-stages
      of the zebrafish (Danio rerio).
AB  - Zebrafish embryos are being increasingly used as model organisms for the
      assessment of single substances and complex environmental samples for regulatory
      purposes. Thus, it is essential to fully understand the xenobiotic metabolism
      during the different life-stages of early development. The aim of the present
      study was to determine arylhydrocarbon receptor (AhR)-mediated activity during
      selected times of early development using qPCR, enzymatic activity through
      measurement of 7-ethoxyresorufin-O-deethylase (EROD) activity, and protein
      expression analysis. In the present study, gene expression of cyp1a, cyp1b1,
      cyp1c1, cyp1c2, and ahr2 as well as EROD activity were investigated up to 120 h
      postfertilization (hpf) after exposure to either beta-naphthoflavone (BNF) or a
      polycyclic aromatic hydrocarbons (PAH)-contaminated sediment extract from Vering
      Kanal in Hamburg (VK). Protein expression was measured at 72 hpf after exposure
      to 20 MUg/L BNF. Altered proteins were identified by matrix assisted laser
      desorption ionization time-of-flight (MALDI-TOF) peptide mass fingerprinting.
      Distinct patterns of basal messenger RNA (mRNA) expression were found for each of
      the cyp1 genes, suggesting specific roles during embryonic development. All
      transcripts were induced by BNF and VK. ahr2 mRNA expression was significantly
      upregulated after exposure to VK. All cyp1 genes investigated showed a temporal
      decline in expression at 72 hpf. The significant decline of Hsp 90beta protein at
      72 hpf after exposure to BNF may suggest an explanation for the decline of cyp1
      genes at this time point as Hsp 90beta is of major importance for the functioning
      of the Ah-receptor. EROD activity measured in embryos was significantly induced
      after 96 hpf of exposure to BNF or VK. Together, these results demonstrate
      distinct temporal patterns of cyp1 genes and protein activities in zebrafish
      embryos as well as show a need to investigate further the xenobiotic
      biotransformation system during early development of zebrafish.

PMID- 25994264
TI  - Characterization of engineered TiO2 nanomaterials in a life cycle and risk
      assessments perspective.
AB  - For the last 10 years, engineered nanomaterials (ENMs) have raised interest to
      industrials due to their properties. They are present in a large variety of
      products from cosmetics to building materials through food additives, and their
      value on the market was estimated to reach $3 trillion in 2014 (Technology
      Strategy Board 2009). TiO2 NMs represent the second most important part of ENMs
      production worldwide (550-5500 t/year). However, a gap of knowledge remains
      regarding the fate and the effects of these, and consequently, impact and risk
      assessments are challenging. This is due to difficulties in not only
      characterizing NMs but also in selecting the NM properties which could contribute
      most to ecotoxicity and human toxicity. Characterizing NMs should thus rely on
      various analytical techniques in order to evaluate several properties and to
      crosscheck the results. The aims of this review are to understand the fate and
      effects of TiO2 NMs in water, sediment, and soil and to determine which of their
      properties need to be characterized, to assess the analytical techniques
      available for their characterization, and to discuss the integration of specific
      properties in the Life Cycle Assessment and Risk Assessment calculations. This
      study underlines the need to take into account nano-specific properties in the
      modeling of their fate and effects. Among them, crystallinity, size, aggregation
      state, surface area, and particle number are most significant. This highlights
      the need for adapting ecotoxicological studies to NP-specific properties via new
      methods of measurement and new metrics for ecotoxicity thresholds.

PMID- 25994266
TI  - PCB remediation in schools: a review.
AB  - Growing awareness of polychlorinated biphenyls (PCBs) in legacy caulk and other
      construction materials of schools has created a need for information on best
      practices to control human exposures and comply with applicable regulations. A
      concise review of approaches and techniques for management of building-related
      PCBs is the focus of this paper. Engineering and administrative controls that
      block pathways of PCB transport, dilute concentrations of PCBs in indoor air or
      other exposure media, or establish uses of building space that mitigate exposure
      can be effective initial responses to identification of PCBs in a building.
      Mitigation measures also provide time for school officials to plan a longer-term
      remediation strategy and to secure the necessary resources. These longer-term
      strategies typically involve removal of caulk or other primary sources of PCBs as
      well as nearby masonry or other materials contaminated with PCBs by the primary
      sources. The costs of managing PCB-containing building materials from assessment
      through ultimate disposal can be substantial. Optimizing the efficacy and cost
      effectiveness of remediation programs requires aligning a thorough understanding
      of sources and exposure pathways with the most appropriate mitigation and
      abatement methods. 

PMID- 25994267
TI  - Adsorbable organic bromine compounds (AOBr) in aquatic samples: a nematode-based
      toxicogenomic assessment of the exposure hazard.
AB  - Elevated levels of adsorbable organic bromine compounds (AOBr) have been detected
      in German lakes, and cyanobacteria like Microcystis, which are known for the
      synthesis of microcystins, are one of the main producers of natural
      organobromines. However, very little is known about how environmental realistic
      concentrations of organobromines impact invertebrates. Here, the nematode
      Caenorhabditis elegans was exposed to AOBr-containing surface water samples and
      to a Microcystis aeruginosa-enriched batch culture (MC-BA) and compared to single
      organobromines and microcystin-LR exposures. Stimulatory effects were observed in
      certain life trait variables, which were particularly pronounced in nematodes
      exposed to MC-BA. A whole genome DNA-microarray revealed that MC-BA led to the
      differential expression of more than 2000 genes, many of which are known to be
      involved in metabolic, neurologic, and morphologic processes. Moreover, the
      upregulation of cyp- and the downregulation of abu-genes suggested the presence
      of chronic stress. However, the nematodes were not marked by negative phenotypic
      responses. The observed difference in MC-BA and microcystin-LR (which impacted
      lifespan, growth, and reproduction) exposed nematodes was hypothesized to be
      likely due to other compounds within the batch culture. Most likely, the exposure
      to low concentrations of organobromines appears to buffer the effects of toxic
      substances, like microcystin-LR.

PMID- 25994269
TI  - Winter time chemical characteristics of aerosols over the Bay of Bengal:
      continental influence.
AB  - As part of the Integrated Campaign for Aerosols, gases and Radiation Budget
      (ICARB) conducted under the Geosphere Biosphere Programme of Indian Space
      Research Organisation, ship-based aerosol sampling was carried out over the
      marine environment of Bay of Bengal (BoB) during the northern winter months of
      December 2008 to January 2009. About 101 aerosol samples were collected, covering
      the region from 3.4 degrees  to 21 degrees  N latitude and 76 degrees  to 98
      degrees  E longitude-the largest area covered-including the south east (SE) BoB
      for the first time. These samples were subjected to gravimetric and chemical
      analysis and the total aerosol loading as well the mass concentration of the
      ionic species namely F(-), Cl(-), Br(-), NO2 (-), NO3 (-), PO4 (2-), SO4 (2-),
      NH4 (+), etc. and the metallic species, Na, Mg, Ca, K, Al, Fe, Mn, Zn, and Pb
      were estimated for each sample. Based on the spatial distribution of individual
      chemical species, the air flow pattern, and airmass back trajectory analysis, the
      source characteristics of aerosols for different regions of BoB were identified.
      Significant level of continental pollution was noticed over BoB during winter.
      While transport of pollution from Indo-Gangetic Plain (IGP) contributed to
      aerosols over north BoB, those over SE BoB were influenced by SE Asia. A
      quantitative study on the wind-induced production of sea salt aerosols and a case
      study on the species dependent effect of rainfall are also presented in this
      paper.

PMID- 25994268
TI  - Simultaneous detection of imidacloprid and parathion by the dual-labeled time
      resolved fluoroimmunoassay.
AB  - A highly sensitive direct dual-labeled time-resolved fluoroimmunoassay (TRFIA) to
      detect parathion and imidacloprid simultaneously in food and environmental
      matrices was developed. Europium (Eu(3+)) and samarium (Sm(3+)) were used as
      fluorescent labels by coupling separately with L1-Ab and A1P1-Ab. Under optimal
      assay conditions, the half-maximal inhibition concentration (IC50) and limit of
      detection (LOD, IC10) were 10.87 and 0.025 MUg/L for parathion and 7.08 and 0.028
      MUg/L for imidacloprid, respectively. The cross-reactivities (CR) were negligible
      except for methyl-parathion (42.4 %) and imidaclothiz (103.4 %). The average
      recoveries of imidacloprid ranged from 78.9 to 104.2 % in water, soil, rice,
      tomato, and Chinese cabbage with a relative standard deviation (RSD) of 2.4 to
      11.6 %, and those of parathion were from 81.5 to 110.9 % with the RSD of 3.2 to
      10.5 %. The results of TRFIA for the authentic samples were validated by
      comparison with gas chromatography (GC) analyses, and satisfactory correlations
      (parathion: R (2) = 0.9918; imidacloprid: R (2) = 0.9908) were obtained. The
      results indicate that the dual-labeled TRFIA is convenient and reliable to detect
      parathion and imidacloprid simultaneously in food and environmental matrices.

PMID- 25994270
TI  - Effect of phosphogypsum on growth, physiology, and the antioxidative defense
      system in sunflower seedlings.
AB  - Phosphogypsum (PG) is the solid waste product of phosphate fertilizer production
      and is characterized by high concentrations of salts, heavy metals, and certain
      natural radionuclides. The work reported in this paper examined the influence of
      PG amendment on soil physicochemical proprieties, along with its potential impact
      on several physiological traits of sunflower seedlings grown under controlled
      conditions. Sunflower seedlings were grown on agricultural soil substrates
      amended with PG at rates of 0, 2.5, and 5 %. The pH of the soil decreased but
      electrical conductivity and organic matter, calcium, phosphorus, sodium, and
      heavy metal contents increased in proportion to PG concentration. In contrast, no
      variations were observed in magnesium content and small increases were recorded
      in potassium content. The effects of PG on sunflower growth, leaf chlorophyll
      content, nutritional status, osmotic regulator content, heavy metal accumulation,
      and antioxidative enzymes were investigated. Concentrations of trace elements in
      sunflower seedlings grown in PG-amended soil were considerably lower than ranges
      considered phytotoxic for vascular plants. The 5 % PG dose inhibited shoot
      extension and accumulation of biomass and caused a decline in total protein
      content. However, chlorophyll, lipid peroxidation, proline and sugar contents,
      and activities of antioxidant enzymes such as superoxide dismutase and catalase
      increased. Collectively, these results strongly support the hypothesis that
      enzymatic antioxidation capacity is an important mechanism in tolerance of PG
      salinity in sunflower seedlings.

PMID- 25994271
TI  - Citrate gold nanoparticle exposure in the marine bivalve Ruditapes philippinarum:
      uptake, elimination and oxidative stress response.
AB  - Gold nanoparticles (AuNPs) are considered an important nano-sized component of
      the twenty-first century. Due to their unique physical and chemical properties,
      they are being used and developed for a wide range of promising applications in
      medicine, biology and chemistry. Notwithstanding their useful aspects, in recent
      years concern has been raised over their ability to enter cells, organelles and
      nuclei and provoke oxidative stress. In a laboratory-based experiment, the non
      target marine bivalve Ruditapes philippinarum was used as a model organism.
      Uptake, elimination and molecular effects under short-term and sub-chronic
      exposure conditions to an environmental relevant concentration (0.75 MUg L(-1))
      of weakly agglomerating citrate AuNPs (~20 nm) were studied. Our results
      demonstrate that at the tested concentration, the particles are readily taken up
      into the digestive gland > gills and can produce significant changes (p < 0.05)
      in oxidative stress and inflammatory response markers, as measured by phase II
      antioxidant enzymes and q-PCR gene expression analysis. However, the overall
      magnitude of responses was low, and oxidative damage was not provoked. Further, a
      significant elimination of Au from the digestive tract within a 7-day
      purification period was observed, with excretion being an important pathway. In
      conclusion, short-term and sub-chronic exposure to an environmental relevant
      concentration of citrate-stabilized AuNPs cannot be considered toxic to our model
      organism, while some further consideration should be given to chronic exposure
      effects.

PMID- 25994272
TI  - Aquatic oil spill cleanup using natural sorbents.
AB  - One of the most popular transportation methods of crude oil is water transport,
      leading to potential spills of these pollutants in the seas and oceans and water
      areas of ports, during their extraction, transportation, transhipment and use.
      The growth of the Lithuanian economy and the expansion of competitiveness were
      hardly imagined without the development of the Klaipeda seaport. However, the
      intensity of shipping and the increase in cargo loading volumes at specialised
      terminals are associated with a higher risk of environmental pollution. To
      achieve a sustainable development of the seaport, it is necessary not only to
      ensure the prevention of potential water pollution but also, if necessary, to use
      environmentally friendly technology for pollution management. The work analyses
      the possibilities related to the collection of oil products from the water
      surface using natural sorbents (peat, wool, moss and straw) and their
      composites.The research of absorbed amount of crude oil and diesel fuel spilled
      on the water surface, while using sorbents and their composites, determined that
      sorbents' composite straw-peat (composition percentage of straw-peat 25-75 %)
      absorbs the major amount of both crude oil (60 % of the spilled volume) and
      diesel fuel (69 % of the spilled volume) comparing to single sorbents and
      sorbents' composite straw-peat (composition percentage of straw-peat 50-50 %).

PMID- 25994273
TI  - Does financial development reduce environmental degradation? Evidence from a
      panel study of 129 countries.
AB  - The purpose of this study is to explore the effect of financial development on
      CO2 emission in 129 countries classified by the income level. A panel CO2
      emission model using urbanisation, GDP growth, trade openness, petroleum
      consumption and financial development variables that are major determinants of
      CO2 emission was constructed for the 1980-2011 period. The results revealed that
      the variables are cointegrated based on the Pedroni cointegration test. The
      dynamic ordinary least squares (OLS) and the Granger causality test results also
      show that financial development can improve environmental quality in the short
      run and long run due to its negative effect on CO2 emission. The rest of the
      determinants, especially petroleum consumption, are determined to be the major
      source of environmental damage in most of the income group countries. Based on
      the results obtained, the investigated countries should provide banking loans to
      projects and investments that can promote energy savings, energy efficiency and
      renewable energy to help these countries reduce environmental damage in both the
      short and long run.

PMID- 25994274
TI  - Assessment of the contamination of marine fauna by chlordecone in Guadeloupe and
      Martinique (Lesser Antilles).
AB  - Chlordecone is an organochlorine pesticide, used in the Lesser Antilles from 1972
      to 1993 to fight against a banana weevil. That molecule is very persistent in the
      natural environment and ends up in the sea with runoff waters. From 2003 to 2013,
      seven campaigns of samplings have been conducted to evaluate the level of
      contamination of fish, crustaceans, and mollusks. The present study is the first
      assessment and the first comparison of the concentrations of chlordecone between
      marine areas, taxonomic groups, and ecological factors like trophic groups or
      preferential habitat of fish species. The four most contaminated marine areas are
      located downstream the contaminated rivers and banana plantations. Crustaceans
      seemed to be more sensitive to the contamination than fish or mollusks. Finally,
      when comparing contamination of fish according to their ecology, we found that
      fish usually living at the border of mangrove and presenting detritivores
      omnivores diets were the most contaminated by chlordecone. These results are
      particularly useful to protect the health of the local population by controlling
      the fishing and the commercialization of seafood products, potentially
      contaminated by chlordecone. 

PMID- 25994275
TI  - Confinement of sows for different periods during lactation: effects on behaviour
      and lesions of sows and performance of piglets.
AB  - Alternatives to farrowing crates with continuous confinement of the sow are
      urgently needed because the animal welfare is negatively impacted. Given the
      increase of herd sizes, practical experience with loose-housing is needed to
      force the implementation of these systems in the field. Next to aspects of labour
      efficiency, detrimental piglet mortality rates that may occur during the first
      days postpartum (pp) is a major criticism. Therefore, loose-housing after a
      crating period limited to the first days pp might be a feasible alternative to
      improve welfare under intensive production conditions. The aim was to investigate
      the effect of crating sows during lactation for different periods on their
      behaviour and integument alterations and on piglets' performance. Gilts from a
      commercial herd were observed from 5 to 26 days pp and housed in farrowing crates
      (1.85*2.50 m) that could be altered between confinement crates and loose-housing
      pens. Animals were divided into three groups, that were either crated
      continuously from birth until weaning (Group A, n=55), until 14 days pp (Group B;
      n=54) or 7 days pp (Group C, n=59). The behaviour of six randomly selected gilts
      per group was video recorded from 5 to 26 days pp and analysed by time sampling
      technique. Lesions on the legs, shoulder and lumbar vertebra were scored on days
      7, 14 and 25 pp. Piglets were weighed weekly, causes of losses recorded and
      weight losses of gilts measured. Not different between groups (P>0.05), animals
      spent 72 to 76% lying laterally, 14 to 17% lying in abdominal or semi-abdominal
      position, 9 to 10% standing and 1 to 3% sitting. B-sows were lying longer in week
      3 and 4 of lactation compared to A- and C-sows (P0.05), whereas almost 90% of the
      losses occurred in the first week pp. In conclusion, loose-housing of lactating
      gilts after a reduced postnatal crating period of 7 days affected neither the
      activity level of the gilts and lesions on the integument nor pre-weaning
      mortality. Therefore, it is recommended to allow sows to move around to some
      extent during the later lactation period.

PMID- 25994276
TI  - Overvaluation of body shape/weight and engagement in non-compensatory weight
      control behaviors in eating disorders: is there a reciprocal relationship?
AB  - BACKGROUND: Overvaluation of body shape/weight is thought to be the core
      psychopathology underlying eating disorders, which propels engagement in non
      compensatory weight-control behaviors. In turn, these behaviors lead to binge
      eating and/or maintenance of low weight thereby reinforcing overvaluation. The
      present study investigated the reciprocal relationship between overvaluation and
      engagement in non-compensatory weight-control behaviors (defined in two ways:
      restrictive eating and compulsive exercise) among women diagnosed with anorexia
      nervosa or bulimia nervosa (N = 237). METHOD: Participants completed clinical
      interviews in which weekly eating disorder symptoms and behaviors were assessed
      over 2 years. RESULTS: Overvaluation on a given week was associated with greater
      engagement in non-compensatory weight-control behaviors during the following
      week. Further, engagement in non-compensatory weight-control behaviors on a given
      week was associated with greater overvaluation during the following week. These
      findings held true regardless of participants' shape/weight concerns (feelings of
      fatness and fat phobia), and eating disorder diagnosis. CONCLUSIONS: Our data
      provide empirical support for key aspects of the transdiagnostic cognitive
      behavioral model of eating disorders and suggest that targeting non-compensatory
      weight-control behaviors in treatment may help alleviate overvaluation and
      shape/weight concerns.

PMID- 25994278
TI  - Psychological distress and the increased risk of falling into poverty: a
      longitudinal study of Australian adults.
AB  - PURPOSE: To identify whether psychological distress is associated with an
      increased risk of falling into poverty, giving a more complete picture of how
      psychological distress affects living standards. METHODS: Longitudinal analysis
      of the nationally representative Household Income and Labour Dynamics in
      Australian (HILDA) survey using Poisson regression models to estimate relative
      risk of falling into income poverty and multidimensional poverty between 2007 and
      2012. The sample was limited to those who were not already in income poverty in
      2007. Psychological distress was identified using the Kessler-10 (K10) scale.
      RESULTS: After adjusting for confounding factors, having moderate psychological
      distress increased the risk of falling into income poverty by 1.62 (95% CI 1.31
      2.01, p < 0.0001) and the risk of falling into multidimensional poverty by 1.85
      (95% CI 1.37-2.48, p < 0.0001); having very high psychological distress increased
      the risk of falling into income poverty by 2.40 (95% CI 1.80-3.20, p < 0.0001)
      and the risk of falling into multidimensional poverty by 3.68 (95% CI 2.63-5.15,
      p < 0.0001), compared to those with low psychological distress. Those who did
      experience income poverty (RR: 1.29, 95% CI 1.04-1.61, p = 0.0210) and those who
      experienced multidimensional poverty (RR: 1.69, 95% CI 1.32-2.17, p < 0.0001) had
      an increased risk of having their level of psychological distress increase
      further compared to those who did not experience poverty. CONCLUSION: To date,
      the increased risk of falling into poverty that is associated with elevated
      levels of psychological distress has been an overlooked burden of the condition.

PMID- 25994279
TI  - Effects of Tris(1,3-dichloro-2-propyl) Phosphate (TDCPP) in Tetrahymena
      Thermophila: Targeting the Ribosome.
AB  - Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in the
      environment, and exposure to TDCPP appears widespread. It has been implicated to
      cause toxicity in vertebrates, but its potential to affect lower-trophic-level
      species remains unknown. In the present study, the ciliated protozoan,
      Tetrahymena thermophila, was used as a model to evaluate toxic effects of TDCPP
      and explore molecular mechanisms by integrating phenotypic observation, RNA-Seq
      and transmission electron microscopy (TEM) Imaging technologies. Exposure to
      0.01, 0.1 or 1 MUM TDCPP for 5 days significantly decreased the relative biomass
      by reducing number of cells, size of cells and quantity of cilia in a dose
      dependent manner. RNA-Seq analysis demonstrated that expression of twenty-one
      ribosome protein genes was down-regulated and these genes were enriched in
      "ribosome" term in KEGG pathway analysis. Furthermore, down-regulation of genes
      expressing ribosome proteins was accompanied by decreased ribosome quantity in
      rough endoplasmic reticulum and cytoplasm and enlarged ribosome size. Therefore,
      taken together, the data from the present study suggest that exposure to TDCPP
      affects growth and reproduction of Tetrahymena thermophila by targeting the
      ribosome. This information might provide insights into critical mechanisms of
      toxic action in other species and lead to useful bioindicators of exposure to
      TDCPP.

PMID- 25994280
TI  - In Silico Investigation of Angiogenesis with Growth and Stress Generation Coupled
      to Local Extracellular Matrix Density.
AB  - Mechanical interactions during angiogenesis, i.e., traction applied by neovessels
      to the extracellular matrix and the corresponding deformation, are important
      regulators of growth and neovascularization. We have previously designed,
      implemented, and validated a coupled model of angiogenesis in which a discrete
      microvessel growth model interacts with a continuous finite element mesh through
      the application of local remodeling sprout stresses (Edgar et al. in Biomech
      Model Mechanobiol, 2014). However, the initial implementation of this framework
      does not take matrix density into account when determined these remodeling
      stresses and is therefore insufficient for the study of angiogenesis within
      heterogeneous matrix environments such as those found in vivo. The objective of
      this study was to implement sensitivity to matrix density in the active stress
      generation within AngioFE in order to allow the study of angiogenic growth within
      a heterogeneous density environment. We accomplished this by scaling active
      sprout stresses relative to local matrix density using a scaling factor
      previously determined from experimental data. We then exercised the new
      functionality of the model by simulating angiogenesis within four different
      scenarios: homogeneous density, a narrow gap model, and matrix density gradient,
      and a construct subjected to repeated loading/unloading and preconditioning.
      These numerical experiments predicted heterogeneous matrix density in the
      initially homogeneous case, the closure and alignment of microvessels along a low
      density gap, the formation of a unique cap-like structure during angiogenesis
      within a density gradient, and the alignment of microvessels in the absence of
      applied load due to preconditioning. The result of these in silico investigations
      demonstrate how matrix heterogeneity affects neovascularization and matrix
      deformation and provides a platform for studying angiogenesis in complicated and
      multi-faceted mechanical environments that microvessels experience in vivo. 

PMID- 25994281
TI  - Temporal Structure of Support Surface Translations Drive the Temporal Structure
      of Postural Control During Standing.
AB  - A healthy biological system is characterized by a temporal structure that
      exhibits fractal properties and is highly complex. Unhealthy systems demonstrate
      lowered complexity and either greater or less predictability in the temporal
      structure of a time series. The purpose of this research was to determine if
      support surface translations with different temporal structures would affect the
      temporal structure of the center of pressure (COP) signal. Eight healthy young
      participants stood on a force platform that was translated in the anteroposterior
      direction for input conditions of varying complexity: white noise, pink noise,
      brown noise, and sine wave. Detrended fluctuation analysis was used to
      characterize the long-range correlations of the COP time series in the AP
      direction. Repeated measures ANOVA revealed differences among conditions (p <
      0.001). The less complex support surface translations resulted in a less complex
      COP compared to normal standing. A quadratic trend analysis demonstrated an
      inverted-u shape across an increasing order of predictability of the conditions
      (p < 0.001). The ability to influence the complexity of postural control through
      support surface translations can have important implications for rehabilitation. 

PMID- 25994282
TI  - Site-specific conjugation of 8-ethynyl-BODIPY to a protein by [2 + 3]
      cycloaddition.
AB  - We report a straightforward synthesis of 8-ethynyl-BODIPY derivatives and their
      potential as fluorescent labeling compounds using an alkyne-azide click chemistry
      approach. The ethynyl substituted BODIPY dyes at the meso-position were reacted
      under Cu(+) catalysis and mild physiological conditions in organic and biological
      model systems using benzyl azide and a Barstar protein which was selectively
      modified by a single amino acid substituted methionine at the N-terminus (Met1) 
      > azidohomoalanine (Aha). Conjugation with the protein and the model azide was
      indicated by a significant blue shift upon formation of the triazole moiety
      system, which allowed easy distinction between free and coupled dyes. This blue
      shift was rationalized by the perpendicular orientation of the triazole relative
      to the chromophore using time dependent density functional theory (TDDFT)
      calculations. A full spectroscopic and thermodynamic characterization of the
      protein revealed that a fluorophore was incorporated without the cross influence
      of protein stability and functional integrity. Furthermore, model reactions of 8
      ethynyl-BODIPY derivatives with benzyl azide under copper-free conditions
      indicate second order kinetics with high rate constants comparable with those
      found for the strain-promoted azide-alkyne cycloaddition (SPAAC). In this way, we
      establish a unique and highly efficient method to introduce alkyne-BODIPY into a
      protein scaffold potentially useful for diverse applications in areas ranging
      from fundamental protein dynamics studies to biotechnology or cell biology. 

PMID- 25994283
TI  - Diet complexity in early life affects survival in released pheasants by altering
      foraging efficiency, food choice, handling skills and gut morphology.
AB  - Behavioural and physiological deficiencies are major reasons why reintroduction
      programmes suffer from high mortality when captive animals are used. Mitigation
      of these deficiencies is essential for successful reintroduction programmes. Our
      study manipulated early developmental diet to better replicate foraging behaviour
      in the wild. Over 2 years, we hand-reared 1800 pheasants (Phasianus colchicus),
      from 1 day old, for 7 weeks under different dietary conditions. In year one, 900
      pheasants were divided into three groups and reared with (i) commercial chick
      crumb, (ii) crumb plus 1% live mealworm or (iii) crumb plus 5% mixed seed and
      fruit. In year two, a further 900 pheasants were divided into two groups and
      reared with (i) commercial chick crumb or (ii) crumb plus a combination of 1%
      mealworm and 5% mixed seed and fruit. In both years, the commercial chick crumb
      acted as a control treatment, whilst those with live prey and mixed seeds and
      fruits mimicking a more naturalistic diet. After 7 weeks reared on these diets,
      pheasants were released into the wild. Postrelease survival was improved with
      exposure to more naturalistic diets prior to release. We identified four
      mechanisms to explain this. Pheasants reared with more naturalistic diets (i)
      foraged for less time and had a higher likelihood of performing vigilance
      behaviours, (ii) were quicker at handling live prey items, (iii) were less
      reliant on supplementary feed which could be withdrawn and (iv) developed
      different gut morphologies. These mechanisms allowed the pheasants to (i) reduce
      the risk of predation by reducing exposure time whilst foraging and allowing more
      time to be vigilant; (ii) be better at handling and discriminating natural food
      items and not be solely reliant on supplementary feed; and (iii) have a better
      gut system to cope with the natural forage after the cessation of supplementary
      feeding in the spring. Learning food discrimination, preference and handling
      skills by the provision of a more naturalistic diet is essential prior to the
      release of pheasants in a reintroduction programme. Subsequent diet, foraging
      behaviour, gut morphology and digestive capabilities all work together as one
      nutritional complex. Simple manipulations during early development can influence
      these characteristics to better prepare an individual for survival upon release.

PMID- 25994284
TI  - Urinary Allantoin Is Elevated in Severe Intraventricular Hemorrhage in the
      Preterm Newborn.
AB  - Germinal matrix intraventricular hemorrhage (IVH) is the most common type of
      intracranial hemorrhage observed in preterm neonates. It is a precursor of poor
      neurocognitive development, cerebral palsy, and death. The pathophysiology is not
      well defined, but damage to the fragile germinal matrix vasculature may be due to
      free radicals generated during inflammation and as a consequence of ischemia
      followed by reperfusion. Assessment of the oxidative stress status in these
      infants is therefore important. Urinary allantoin concentration was measured in
      preterm neonates as a marker of oxidative stress associated with IVH. Urine was
      collected from 44 preterm neonates at four time points between 24 and 72 hours of
      life (HOL), and the allantoin content was determined by gas chromatography mass
      spectrometry (GCMS). Records were retrospectively reviewed, and the incidence and
      severity of IVH was categorized as follows: no IVH (n = 24), mild (grade 1-2) IVH
      (n = 13), and severe (grade 3-4) IVH (n = 7). Neonates with severe IVH showed
      significantly elevated allantoin levels vs subjects with no IVH from 36 HOL
      (0.098 +/- 0.013 MUmol and 0.043 +/- 0.007 MUmol, respectively, p = 0.002). The
      allantoin concentration remained elevated even at 72 HOL (0.079 +/- 0.014 MUmol
      and 0.033 +/- 0.008 MUmol, respectively, p = 0.021). There were no significant
      differences in allantoin levels in the no IVH and mild IVH groups. IVH was
      diagnosed by head imaging on average at about 11th postnatal day. Urinary
      allantoin levels were significantly elevated during the first 3 days of life in
      the neonates subsequently diagnosed with severe IVH, suggesting that oxidative
      stress might be a crucial factor in IVH pathogenesis. Further studies are needed
      to assess the usefulness of urinary allantoin in early identification of preterm
      infants at risk for or with severe IVH and monitoring of the response to
      interventions designed to prevent or treat it.

PMID- 25994285
TI  - Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have
      Distinct Alternatively Spliced mRNA Profiles in the Blood: a Pilot RNA-seq Study.
AB  - Whole transcriptome studies have used 3'-biased expression microarrays to study
      genes regulated in the blood of stroke patients. However, alternatively spliced
      messenger RNA isoforms have not been investigated for ischemic stroke or
      intracerebral hemorrhage (ICH) in animals or humans. Alternative splicing is the
      mechanism whereby different combinations of exons of a single gene produce
      distinct mRNA and protein isoforms. Here, we used RNA sequencing (RNA-seq) to
      determine if alternative splicing differs for ICH and cardioembolic, large vessel
      and lacunar causes of ischemic stroke compared to controls. RNA libraries from 20
      whole blood samples were sequenced to 200 M 2 * 100 bp reads using Illumina
      sequencing-by-synthesis technology. Differential alternative splicing was
      assessed using one-way analysis of variance (ANOVA), and differential exon usage
      was calculated. Four hundred twelve genes displayed differential alternative
      splicing among the groups (false discovery rate, FDR; p < 0.05). They were
      involved in cellular immune response, cell death, and cell survival pathways.
      Distinct expression signatures based on usage of 308 exons (292 genes)
      differentiated the groups (p < 0.0005; fold change >|1.2|). This pilot study
      demonstrates that alternatively spliced genes from whole blood differ in ICH
      compared to ischemic stroke and differ between different ischemic stroke
      etiologies. These results require validation in a separate cohort. 

PMID- 25994286
TI  - Mortality among a Cohort of Persons with an Intellectual Disability in New South
      Wales, Australia.
AB  - OBJECTIVES: The main objective of the study was to compare mortality for people
      with an intellectual disability (ID) to the general population in New South Wales
      (NSW), Australia. A second objective was to provide mortality data for people
      with an intellectual disability from NSW in a standardized format, which allows
      for international comparisons of the mortality of people with an intellectual
      disability. DESIGN AND SETTING: The study was a longitudinal cohort study linking
      retrospective data from the population databases of the NSW Department of Ageing,
      Disability and Home Care (ADHC) Intellectual Disability Services Dataset
      (intellectual disability cohort) to the mortality data set of the NSW Registry of
      Births, Deaths and Marriages (RBDM) for the period 1 June 2005 to 31 December
      2011. PARTICIPANTS: The two groups of interest for this study were persons with
      an intellectual disability recorded in the intellectual disability cohort (953
      deaths among 42,219 persons over 270,649 person-years of observation) and the
      rest of the NSW population (312,649 deaths among over 7,218,529 persons [2011
      population] and 45,818,946 person-years of observation). MAIN OUTCOME MEASURES:
      In this study, we compared the intellectual disability cohort with the rest of
      the NSW population using age-adjusted death rates (ADRs), standardized mortality
      ratios (SMRs) and age standardized death rates (ASDRs) based upon the World
      Health Organization (WHO) standard population. RESULTS: We found a significantly
      higher mortality in a cohort of people with an intellectual disability compared
      to the rest of the NSW population. The intellectual disability cohort compared to
      the rest of the NSW population had an SMR of 2.48 for all ages and an SMR of 3.15
      for those aged 5-69 years. We also found an SMR for females (4.26) with an
      intellectual disability that was significantly higher than that for males (2.52)
      with an intellectual disability. The ASDR for the intellectual disability cohort
      was 4.04 (deaths per 1000) and the ASDR for the rest of the NSW population was
      1.58, giving a comparative mortality ratio of 2.55. CONCLUSIONS: Our findings
      indicate excess mortality of people with an intellectual disability when compared
      to the general population. They also indicate that females with an intellectual
      disability have a higher relative mortality compared to female same-aged general
      population peers, and also males with an intellectual disability, a finding
      replicated in other similar cohort studies. For international comparison using
      the WHO standard population, our intellectual disability cohort (ages 5-69 years)
      had a mortality of 4.04 deaths per 1000.

PMID- 25994287
TI  - Co-morbidity Between Gambling Problems and Depressive Symptoms: A Longitudinal
      Perspective of Risk and Protective Factors.
AB  - In both adolescents and adults, gambling problems and depressive symptoms co
      occur and share some common risk factors (e.g., impulsivity and socio-family
      risk). However, little is known about (1) the developmental course of the co
      morbidity of these problems; (2) variables that may moderate the effect of these
      common risk factors on gambling problems and depressive symptoms. Of specific
      interest could be individuals' social relationships with significant others such
      as parents and friends, because research shows that they moderate the effect of
      other risk factors on gambling problems and depressive symptoms. The goals of
      this study were to: (a) identify developmental pathways for gambling problems and
      depressive symptoms, with a focus on co-morbidity; (b) assess the moderating
      effect of relationship quality with parents and friends on the link between
      common risk factors and the trajectories of gambling problems and depressive
      symptoms. Study participants were 878 males. Predictors were assessed during
      childhood and adolescence and gambling problems and depressive symptoms were
      assessed in late adolescence and young adulthood. Latent class analysis revealed
      four distinct joint trajectories of gambling problems and depressive symptoms.
      Subsequent logistic regression revealed that impulsivity predicted membership in
      all pathogenic trajectories, and quality of the relationship with parents
      predicted membership in depressogenic trajectories. In addition, we found that
      the membership in the comorbid trajectory can be predicted by an interaction
      between friendship quality and socio-family risk. 

PMID- 25994288
TI  - The post-2015 development agenda for diabetes in sub-Saharan Africa: challenges
      and future directions.
AB  - BACKGROUND: Diabetes is one of the non-communicable diseases (NCDs) which is
      rising significantly across sub-Saharan African (SSA) countries and posing a
      threat to the social, economic, and cultural fabric of the SSA population. The
      inclusion of NCDs into the post-2015 development agenda along with the global
      monitoring framework provides an opportunity to monitor progress of development
      programmes in developing countries. This paper examines challenges associated
      with dealing with diabetes within the development agenda in SSA and explores some
      policy options. DESIGN: This conceptual review draws from a range of works
      published in Medline and the grey literature to advance the understanding of the
      post-2015 development agenda and how it relates to NCDs. The paper begins with
      the burden of diabetes in sub-Sahara Africa and then moves on to examine
      challenges associated with diabetes prevention, treatment, and management in
      Africa. It finishes by exploring policy implications. RESULTS: With regards to
      development programmes on NCDs in the SSA sub-continent, several challenges
      exist: 1) poor documentation of risk factors, 2) demographic transitions (rapid
      urbanisation and ageing), 3) the complementary role of traditional healers, 4)
      tuberculosis and the treatment of the acquired immunodeficiency syndrome as risk
      factors for diabetes, 5) diabetes in complex emergencies, 6) diabetes as an
      international development priority and not a policy agenda for many SSA
      countries, and 7) poorly regulated food and beverage industry. CONCLUSION: For
      the post-2015 development agenda for NCDs to have an impact, sufficient
      investments will be needed to address legislative, technical, human, and fiscal
      resource constraints through advocacy, accountability, political leadership, and
      effective public-private partnership. Striking the right balance between
      competing demands and priorities, policies, and implementation strategies hold
      the key to an effective response to diabetes in SSA countries.

PMID- 25994289
TI  - Profiling of cardiac beta-adrenoceptor subtypes in the cardiac left ventricle of
      rats with metabolic syndrome: Comparison with streptozotocin-induced diabetic
      rats.
AB  - Little is known about metabolic syndrome (MetS)-associated cardiomyopathy,
      especially in relation to the role and contribution of beta-adrenoceptor (beta
      AR) subtypes. Therefore, we examined the roles of beta-AR subtypes in the cardiac
      function of rats with MetS (MetS group) and compared it with that of rats with
      streptozotocin (STZ)-induced diabetes (STZ group). Compared with the normal
      control rats, the protein levels of cardiac beta1- and beta2-AR in the MetS group
      were significantly decreased and with no changes in their mRNA levels, whereas
      the protein levels of beta3-AR were similar to those of the controls. However, as
      shown previously, the protein levels of cardiac beta1- and beta2-AR in the STZ
      group were decreased, whereas the beta3-AR levels were significantly increased by
      comparison with the controls. Additionally, the mRNA levels of beta2- and beta3
      AR were increased, but beta1-AR mRNA was decreased in the STZ group. Furthermore,
      left ventricular developed pressure responses to beta3-AR agonist BRL37344 were
      increased in the STZ group but not in the MetS group, whereas for both groups,
      the responses to noradrenaline were not different from those of the controls.
      However, the response to stimulation with high concentrations of fenoterol was
      depressed in the MetS group, compared with the controls, but not in the STZ
      group. Consequently, our data suggest that the contribution of the beta-AR system
      to cardiac dysfunction in the rats with MetS is not the same as that in the STZ
      group, although they have similar cardiac dysfunction with similar
      ultrastructural changes to the myocardium. 

PMID- 25994291
TI  - Towards a better understanding of honeycomb alternating magnetic networks.
AB  - Two new two-dimensional homometallic compounds {[M2(bpm)(ox)2]n.5nH2O} with M =
      Co(II) (1) and Zn(II) (2) and the mononuclear nickel(II) complex
      [Ni(bpm)2(ox)].2H2O (3) [bpm = 2,2'-bipyrimidine and ox = oxalate] have been
      prepared and structurally characterized. 1 and 2 are isostructural compounds
      whose structures are made up of oxalate-bridged M(II) cations cross-linked by bis
      bidentate bpm molecules to afford a honeycomb layered network extending in the
      crystallographic ab plane. The layers are eclipsed along the crystallographic c
      axis and show graphitic-like interactions between the bpm rings. The three
      dimensional supramolecular network deriving from such interactions is
      characterized by hexagonal-shaped channels extending in the same direction. Each
      M(II) ion in 1 and 2 is tris-chelated with four oxygen atoms from two oxalate
      groups and two bpm-nitrogen atoms building a distorted octahedral surrounding.
      The reduced values of the angles subtended by the bis-chelating bpm [77.69(8) (1)
      and 76.59(8) degrees  (2)] and oxalate [79.69(6) (1) and 80.01(5) degrees  (2)]
      are the main factors accounting for this distortion. The values of the metal
      metal separation through bridging bpm are 5.6956(7) (1) and 5.7572(9) A (2),
      whereas those across the bis-bidentate oxalate are 5.4306(4) (1) and 5.4058(5) A
      (2). 3 is a neutral mononuclear nickel(II) complex where each metal ion is six
      coordinate with four nitrogen atoms from two bpm ligands in a cis arrangement and
      two oxalate-oxygen atoms building a somewhat distorted octahedral surrounding.
      The values of the angles subtended at the nickel(II) ion by bpm and oxalate are
      78.14(4) and 80.95(5) degrees , respectively. The magnetic properties of 1 have
      been investigated in the temperature range 1.9-295 K. They are typical of an
      overall antiferromagnetic coupling with a maximum of the magnetic susceptibility
      at 22.0 K. The analysis of the susceptibility data of 1 through an effective spin
      Hamiltonian allowed a satisfactory simulation in the temperature range 10-295 K
      with the best-fit parameters lambda = -110 cm(-1), alpha = 1.1, |Delta| = 400 cm(
      1), J(ox) = -11.1 cm(-1) and J(bpm) = -5.0 cm(-1). The values of the
      antiferromagnetic coupling through bpm and ox in 1 have also been supported by
      electronic structure calculations based on Density Functional Theory (DFT) and
      they compare well with those reported in the literature for bpm-bridged
      dicobalt(II) complexes and oxalate-bridged cobalt(II) chains.

PMID- 25994290
TI  - Characterization of a novel chicken muscle disorder through differential gene
      expression and pathway analysis using RNA-sequencing.
AB  - BACKGROUND: Improvements in poultry production within the past 50 years have led
      to increased muscle yield and growth rate, which may be contributing to an
      increased rate and development of new muscle disorders in chickens. Previously
      reported muscle disorders and conditions are generally associated with poor meat
      quality traits and have a significant negative economic impact on the poultry
      industry. Recently, a novel myopathy phenotype has emerged which is characterized
      by palpably "hard" or tough breast muscle. The objective of this study is to
      identify the underlying biological mechanisms that contribute to this emerging
      muscle disorder colloquially referred to as "Wooden Breast", through the use of
      RNA-sequencing technology. METHODS: We constructed cDNA libraries from five
      affected and six unaffected breast muscle samples from a line of commercial
      broiler chickens. After paired-end sequencing of samples using the Illumina Hiseq
      platform, we used Tophat to align the resulting sequence reads to the chicken
      reference genome and then used Cufflinks to find significant changes in gene
      transcript expression between each group. By comparing our gene list to
      previously published histology findings on this disorder and using Ingenuity
      Pathways Analysis (IPA(r)), we aim to develop a characteristic gene expression
      profile for this novel disorder through analyzing genes, gene families, and
      predicted biological pathways. RESULTS: Over 1500 genes were differentially
      expressed between affected and unaffected birds. There was an average of
      approximately 98 million reads per sample, across all samples. Results from the
      IPA analysis suggested "Diseases and Disorders" such as connective tissue
      disorders, "Molecular and Cellular Functions" such as cellular assembly and
      organization, cellular function and maintenance, and cellular movement,
      "Physiological System Development and Function" such as tissue development, and
      embryonic development, and "Top Canonical Pathways" such as, coagulation system,
      axonal guidance signaling, and acute phase response signaling, are associated
      with the Wooden Breast disease. CONCLUSIONS: There is convincing evidence by RNA
      seq analysis to support localized hypoxia, oxidative stress, increased
      intracellular calcium, as well as the possible presence of muscle fiber-type
      switching, as key features of Wooden Breast Disease, which are supported by
      reported microscopic lesions of the disease.

PMID- 25994292
TI  - Production of biologically active scFv and VHH antibody fragments in
      Bifidobacterium longum.
AB  - Bifidobacteria constitute a significant part of healthy intestinal microbiota in
      adults and infants and present a promising platform for construction of
      genetically modified probiotic agents for treatment of gastrointestinal
      disorders. In this study, three strains of Bifidobacterium longum were
      constructed that express and secrete biologically active single-chain antibodies
      against human TNF-alpha and Clostridium difficile exotoxin A. Anti-TNF-alpha scFv
      antibody D2E7 was produced at the level of 25 MUg L(-1) in broth culture and was
      mostly retained in the cytoplasm, while VHH-type antibodies A20.1 and A26.8
      against C. difficile exotoxin A were produced at the levels of 0.3-1 mg L(-1) and
      secreted very efficiently. The biological activity of both antibody types was
      demonstrated in the mammalian cell-based assays. Expression of A20.1 and A26.8
      was also observed in vivo after intragastric administration of transformed B.
      longum strains to (C57/BL6 * DBA/2)F1 mice. The obtained B. longum strains may
      serve as prototypes for construction of novel probiotic medications against
      inflammatory bowel disease and C. difficile-associated disease. 

PMID- 25994293
TI  - Bioeconomic analysis of child-targeted subsidies for artemisinin combination
      therapies: a cost-effectiveness analysis.
AB  - The Affordable Medicines Facility for malaria (AMFm) was conceived as a global
      market-based mechanism to increase access to effective malaria treatment and
      prolong effectiveness of artemisinin. Although results from a pilot
      implementation suggested that the subsidy was effective in increasing access to
      high-quality artemisinin combination therapies (ACTs), the Global Fund has
      converted AMFm into a country-driven mechanism whereby individual countries could
      choose to fund the subsidy from within their country envelopes. Because the
      initial costs of the subsidy in the pilot countries was higher than expected,
      countries are also exploring alternatives to a universal subsidy, such as
      subsidizing only child doses. We examined the incremental cost-effectiveness of a
      child-targeted policy using an age-structured bioeconomic model of malaria from
      the provider perspective. Because the vast majority of malaria deaths occur in
      children, targeting children could potentially improve the cost-effectiveness of
      the subsidy, though it would avert significantly fewer deaths. However, the
      benefits of a child-targeted subsidy (i.e. deaths averted) are eroded as leakage
      (i.e. older individuals taking young child-targeted doses) increases, with few of
      the benefits of a universal subsidy gained (i.e. reductions in overall
      prevalence). Although potentially more cost-effective, a child-targeted subsidy
      must contain measures to reduce the possibility of leakage.

PMID- 25994295
TI  - An integrative method for testing form-function linkages and reconstructed
      evolutionary pathways of masticatory specialization.
AB  - Morphology serves as a ubiquitous proxy in macroevolutionary studies to identify
      potential adaptive processes and patterns. Inferences of functional significance
      of phenotypes or their evolution are overwhelmingly based on data from living
      taxa. Yet, correspondence between form and function has been tested in only a few
      model species, and those linkages are highly complex. The lack of explicit
      methodologies to integrate form and function analyses within a deep-time and
      phylogenetic context weakens inferences of adaptive morphological evolution, by
      invoking but not testing form-function linkages. Here, we provide a novel
      approach to test mechanical properties at reconstructed ancestral nodes/taxa and
      the strength and direction of evolutionary pathways in feeding biomechanics, in a
      case study of carnivorous mammals. Using biomechanical profile comparisons that
      provide functional signals for the separation of feeding morphologies, we
      demonstrate, using experimental optimization criteria on estimation of strength
      and direction of functional changes on a phylogeny, that convergence in
      mechanical properties and degree of evolutionary optimization can be decoupled.
      This integrative approach is broadly applicable to other clades, by using
      quantitative data and model-based tests to evaluate interpretations of function
      from morphology and functional explanations for observed macroevolutionary
      pathways.

PMID- 25994294
TI  - Modulation of cell function by electric field: a high-resolution analysis.
AB  - Regulation of cell function by a non-thermal, physiological-level electromagnetic
      field has potential for vascular tissue healing therapies and advancing hybrid
      bioelectronic technology. We have recently demonstrated that a physiological
      electric field (EF) applied wirelessly can regulate intracellular signalling and
      cell function in a frequency-dependent manner. However, the mechanism for such
      regulation is not well understood. Here, we present a systematic numerical study
      of a cell-field interaction following cell exposure to the external EF. We use a
      realistic experimental environment that also recapitulates the absence of a
      direct electric contact between the field-sourcing electrodes and the cells or
      the culture medium. We identify characteristic regimes and present their
      classification with respect to frequency, location, and the electrical properties
      of the model components. The results show a striking difference in the frequency
      dependence of EF penetration and cell response between cells suspended in an
      electrolyte and cells attached to a substrate. The EF structure in the cell is
      strongly inhomogeneous and is sensitive to the physical properties of the cell
      and its environment. These findings provide insight into the mechanisms for
      frequency-dependent cell responses to EF that regulate cell function, which may
      have important implications for EF-based therapies and biotechnology development.

PMID- 25994296
TI  - Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat
      model of emphysema.
AB  - Hyperpolarized (83)Kr surface quadrupolar relaxation (SQUARE) generates MRI
      contrast that was previously shown to correlate with surface-to-volume ratios in
      porous model surface systems. The underlying physics of SQUARE contrast is
      conceptually different from any other current MRI methodology as the method uses
      the nuclear electric properties of the spin I = 9/2 isotope (83)Kr. To explore
      the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI
      SQUARE contrast was acquired in excised rat lungs obtained from an elastase
      induced model of emphysema. A significant (83)Kr T1 relaxation time increase in
      the SQUARE contrast was found in the elastase-treated lungs compared with the
      baseline data from control lungs. The SQUARE contrast suggests a reduction in
      pulmonary surface-to-volume ratio in the emphysema model that was validated by
      histology. The finding supports usage of (83)Kr SQUARE as a new biomarker for
      surface-to-volume ratio changes in emphysema. 

PMID- 25994297
TI  - Using model-based proposals for fast parameter inference on discrete state space,
      continuous-time Markov processes.
AB  - Bayesian statistics provides a framework for the integration of dynamic models
      with incomplete data to enable inference of model parameters and unobserved
      aspects of the system under study. An important class of dynamic models is
      discrete state space, continuous-time Markov processes (DCTMPs). Simulated via
      the Doob-Gillespie algorithm, these have been used to model systems ranging from
      chemistry to ecology to epidemiology. A new type of proposal, termed 'model-based
      proposal' (MBP), is developed for the efficient implementation of Bayesian
      inference in DCTMPs using Markov chain Monte Carlo (MCMC). This new method, which
      in principle can be applied to any DCTMP, is compared (using simple
      epidemiological SIS and SIR models as easy to follow exemplars) to a standard
      MCMC approach and a recently proposed particle MCMC (PMCMC) technique. When
      measurements are made on a single-state variable (e.g. the number of infected
      individuals in a population during an epidemic), model-based proposal MCMC (MBP
      MCMC) is marginally faster than PMCMC (by a factor of 2-8 for the tests
      performed), and significantly faster than the standard MCMC scheme (by a factor
      of 400 at least). However, when model complexity increases and measurements are
      made on more than one state variable (e.g. simultaneously on the number of
      infected individuals in spatially separated subpopulations), MBP-MCMC is
      significantly faster than PMCMC (more than 100-fold for just four subpopulations)
      and this difference becomes increasingly large.

PMID- 25994298
TI  - Punctuated equilibrium in the large-scale evolution of programming languages.
AB  - The analogies and differences between biological and cultural evolution have been
      explored by evolutionary biologists, historians, engineers and linguists alike.
      Two well-known domains of cultural change are language and technology. Both share
      some traits relating the evolution of species, but technological change is very
      difficult to study. A major challenge in our way towards a scientific theory of
      technological evolution is how to properly define evolutionary trees or clades
      and how to weight the role played by horizontal transfer of information. Here, we
      study the large-scale historical development of programming languages, which have
      deeply marked social and technological advances in the last half century. We
      analyse their historical connections using network theory and reconstructed
      phylogenetic networks. Using both data analysis and network modelling, it is
      shown that their evolution is highly uneven, marked by innovation events where
      new languages are created out of improved combinations of different structural
      components belonging to previous languages. These radiation events occur in a
      bursty pattern and are tied to novel technological and social niches. The method
      can be extrapolated to other systems and consistently captures the major classes
      of languages and the widespread horizontal design exchanges, revealing a
      punctuated evolutionary path. 

PMID- 25994299
TI  - Circadian clocks optimally adapt to sunlight for reliable synchronization.

PMID- 25994300
TI  - Skin fibrosis correlates with circulating thyrotropin levels in systemic
      sclerosis: translational association with Hashimoto's thyroiditis.
AB  - Systemic sclerosis (SSc) is a connective tissue disease, characterized by
      cutaneous and multi-organ fibrosis, and vascular abnormalities. Skin thickening
      is a characteristic feature of SSc and resembles myxedematous skin. Our aim was
      to correlate the degree of skin involvement in SSc patients with serum TSH
      levels, since TSH receptors are widely expressed in human tissues, including the
      skin. In this cross-sectional study, we enrolled 70 SSc patients, all females
      with a mean age of 47 +/- 11 year. Thirty-five age- and sex-matched HT patients
      were recruited, as controls. Subjects under L-thyroxine therapy and/or with
      positive anti-TSH receptor antibodies were excluded. In all subjects, we measured
      serum TSH, FT4, and free tri-iodothyronine (FT3) levels. Skin thickness was
      evaluated using the modified Rodnan total skin score (mRSS). mRSS averaged 14 +/-
      9 for SSc and 4 +/- 6 for HT patients. TSH levels positively correlated with skin
      scores in both SSc and HT patients groups. In SSc patients, FT3 and FT4 showed an
      inverse correlation with mRSS, while in HT only FT4 levels showed this inverse
      significance. When divided by cutaneous extent, SSc patients with diffuse disease
      form had higher TSH serum levels compared to those with the limited form;
      additionally, the correlations between TSH, FT4, and mRSS reached statistical
      significance. Our preliminary data clearly indicate that serum TSH is higher in
      SSc patients with more severe skin disease, and significantly correlate with the
      mRSS. Therefore, TSH could play a role in the development of cutaneous changes in
      SSc patients.

PMID- 25994301
TI  - gammadelta Tau cells enhance B cells for antibody production in Hashimoto's
      thyroiditis, and retinoic acid induces apoptosis of the gammadelta Tau cell.
AB  - TCR gammadelta(+) Tau cells are important in the pathogenesis of inflammatory and
      autoimmune conditions. This study investigated the effect of gammadelta T cells
      on autoantibody production in patients with Hashimoto's thyroiditis (HT). A total
      of 148 subjects were enrolled, including 99 patients with HT, 5 with simple
      goiters, and 44 healthy controls. Peripheral blood and thyroid mononuclear cells
      were subjected to flow cytometric analysis. Thyroid tissues underwent
      immunofluorescent staining and immunohistochemistry for gammadelta T cells and
      anti-thyroid antibody detection. Antibody production was measured by ELISA and
      automated chemiluminescent immunoassays. And activation and apoptosis of
      peripheral blood gammadeltaT cells and B cells were measured by flow cytometric
      analysis. The percentage of gammadelta T cells were greater in thyroid tissue
      from HT patients than that of goiter patients (n = 5, 5.33 +/- 1.20 vs. 2.07 +/-
      0.44 %; P < 0.05), with the Vdelta1(+) gammadelta T cell subset especially
      dominant. Frequencies of CD69 (8.42 +/- 1.08 vs. 1.60 +/- 0.38 %, P < 0.001), HLA
      DR (58.12 +/- 6.36 vs. 37.82 +/- 3.70 %, P < 0.05), CD40L (1.58 +/- 0.35 vs. 0.15
      +/- 0.05 %, P < 0.01), and ICOS (2.78 +/- 0.66 vs. 0.28 +/- 0.13 %, P < 0.01)
      expressed on gammadelta T cells from HT patients (n = 19) were significantly
      increased compared with those of healthy controls (n = 15). More importantly,
      gammadelta T cells from HT patients enhanced B cells for antibody production, and
      all-trans retinoic acid (ATRA) treatment inhibited the effect by inducing
      apoptosis of gammadelta Tau cells. gammadelta Tau cells appear to play an
      important role in the pathogenesis of HT, and ATRA might be an effective
      regulator for HT patients. 

PMID- 25994302
TI  - Does corneal hysteresis correlate with endothelial cell density?
AB  - BACKGROUND: Our aim was to determine if there is a correlation between corneal
      biomechanical properties, endothelial cell count, and corneal pachymetry in
      healthy corneas. MATERIAL/METHODS: Ninety-two eyes of all subjects underwent
      complete ocular examination, including intraocular pressure measurement by
      Goldmann applanation tonometer, objective refraction, and slit-lamp
      biomicroscopy. Topographic measurements and corneal pachymetry were performed
      using a Scheimpflug-based (Pentacam, Oculus, Germany) corneal topographer.
      Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured with an
      Ocular Response Analyzer (ORA, Reichert Ophthalmic Instruments, Buffalo, NY).
      Endothelial cell count measurement was done using a specular microscope
      (CellChek, Konan, USA). RESULTS: Right eye values of the subjects were taken for
      the study. The mean CH was 11.5+/-1.7 mmHg and the mean CRF was 11.2+/-1.4 mmHg.
      Mean intraocular pressure was 15.3+/-2.3 mmHg. The mean endothelial cell count
      was 2754+/-205 cells/mm2. No correlation was found between biomechanical
      properties of cornea and endothelial cell count. There was a significant positive
      correlation between CH, CRF, and corneal thickness (p<0.001; r=0.79).
      CONCLUSIONS: The corneal biomechanical properties significantly correlated with
      corneal thickness. We found no correlation between CH and CRF with the
      endothelial cell density in normal subjects.

PMID- 25994304
TI  - The state of play in child and adolescent mental healthcare services (England):
      not in front of the children?

PMID- 25994303
TI  - Predictive value of dynamic renal resistive index (DRIN) for renal outcome in
      type 2 diabetes and essential hypertension: a prospective study.
AB  - BACKGROUND: Hypertension (EH) and type 2 diabetes (T2DM) are major causes of
      chronic kidney disease (CKD) and identification of predictors of CKD onset is
      advisable. We aimed to assess whether dynamic renal resistive index (DRIN), as
      well as other markers of systemic vascular damage, are able to predict
      albuminuria onset and estimated glomerular filtration rate (eGFR) decline in
      patients with T2DM or EH. METHODS: In this prospective observational cohort
      study, 27 T2DM and 43 EH patients, free of CKD at baseline, were followed-up for
      4.1 +/- 0.6 years. Resistive Index (RI), endothelium-dependent (FMD) and
      independent vasodilation in the brachial artery (after glyceryl trinitrate - GTN 
      25 MUg s.l.), carotid-femoral Pulse Wave Velocity (PWV), Augmentation Index
      (AIx), DRIN (%RI change after GTN 25 MUg s.l.) were evaluated. RESULTS: Patients
      developing microalbuminuria were older, more frequently T2DM, with higher UACR at
      baseline, and showed higher DRIN (-2.8 +/- 6.7 vs -10.6 +/- 6.4 %, p = 0.01) and
      PWV (9.9 +/- 1.3 vs 7.9 +/- 1.5 m/s, p = 0.004) at baseline. The best predictors
      of microalbuminuria onset were DRIN > -5.16 % in T2DM (sensitivity 0.83,
      specificity 0.80) and PWV > 8.6 m/s in EH (sensitivity 0.96, specificity 1.00).
      Individuals whose eGFR declined (n = 27) had higher eGFR at baseline, but similar
      vascular characteristics; however in EH showing eGFR decline, baseline DRIN and
      PWV were higher. PWV showed a steeper progression during follow-up in patients
      developing albuminuria (Visit-outcome interaction: p = 0.01), while DRIN was
      early compromised but no further impaired (Visit-outcome interaction: p = 0.04).
      CONCLUSIONS: PWV and DRIN are able to predict microalbuminuria onset in newly
      diagnosed EH and T2DM. DRIN is early compromised in T2DM patients developing
      microalbuminuria.

PMID- 25994306
TI  - WITHDRAWN: Botulinum toxin for subacute/chronic neck pain.

PMID- 25994305
TI  - WITHDRAWN: Medicinal and injection therapies for mechanical neck disorders.

PMID- 25994307
TI  - WITHDRAWN: Arthroplasty versus fusion in single-level cervical degenerative disc
      disease.

PMID- 25994308
TI  - Aortic 18F-FDG uptake in patients suffering from granulomatosis with
      polyangiitis.
AB  - PURPOSE: The objective of the study was to systematically assess aortic
      inflammation in patients with granulomatosis with polyangiitis (GPA) using (18)F
      2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT.
      METHODS: Aortic inflammation was studied in PET/CT scans obtained from 21
      patients with GPA; 14 patients with sarcoidosis were included as disease
      controls, 7 patients with stage I or II head and neck carcinoma ascertained
      during routine clinical practice were used as healthy controls (HC) and 5
      patients with large vessel vasculitis (LVV) were used as positive controls.
      Aortic (18)F-FDG uptake was expressed as the blood-normalized maximum
      standardized uptake value (SUVmax), known as the target to background ratio (mean
      TBRmax). RESULTS: The mean TBRmax (interquartile range) of the aorta in patients
      with GPA, sarcoidosis, HC and LVV were 1.75 (1.32-2.05), 1.62 (1.54-1.74), 1.29
      (1.22-1.52) and 2.03 (1.67-2.45), respectively. The mean TBRmax was significantly
      higher in patients suffering from GPA or LVV compared to HC (p < 0.05 and p <
      0.005, respectively) and tended to be higher in patients suffering from
      sarcoidosis, but this did not reach statistical significance (p = 0.098). The
      mean TBRmax of the most diseased segment was significantly higher compared to HC
      [1.57 (1.39-1.81)] in LVV patients [2.55 (2.22-2.82), p < 0.005], GPA patients
      [2.17 (1.89-2.83), p < 0.005] and patients suffering from sarcoidosis [2.04 (1.88
      2.20), p < 0.05]. In GPA patients, the mean TBRmax of the aorta was significantly
      higher in patients with previous renal involvement [2.01 (1.69-2.53)] compared to
      patients without renal involvement in the past [1.60 (1.51-1.80), p < 0.05].
      Interrater reproducibility with a second reader was high (all intraclass
      correlation coefficients >0.9). CONCLUSION: Patients suffering from GPA show
      marked aortic FDG uptake.

PMID- 25994309
TI  - Synergetic antibacterial activity of reduced graphene oxide and boron doped
      diamond anode in three dimensional electrochemical oxidation system.
AB  - A 100% increment of antibacterial ability has been achieved due to significant
      synergic effects of boron-doped diamond (BDD) anode and reduced graphene oxide
      (rGO) coupled in a three dimensional electrochemical oxidation system. The rGO,
      greatly enhanced by BDD driven electric field, demonstrated strong antibacterial
      ability and even sustained its excellent performance during a reasonable period
      after complete power cut in the BDD-rGO system. Cell damage experiments and TEM
      observation confirmed much stronger membrane stress in the BDD-rGO system, due to
      the faster bacterial migration and charge transfer by the expanded electro field
      and current-carrying efficiency by quantum tunnel. Reciprocally the hydroxyl
      radical production was eminently promoted with expanded area of electrodes and
      delayed recombination of the electron-hole pairs in presence of the rGO in the
      system. This implied a huge potential for practical disinfection with integration
      of the promising rGO and the advanced electrochemical oxidation systems. 

PMID- 25994311
TI  - The promotion effect of isolated potassium atoms with hybridized orbitals in
      catalytic oxidation.
AB  - The nature of the promotion effect of isolated potassium atoms anchored on
      surfaces of a Hollandite manganese oxide was investigated by studying their
      geometric and electronic structures. The results reveal that the surface isolated
      potassium atoms with hybridized d-sp orbitals specifically promote oxygen
      activation, so enhancing the low-temperature reactivity in catalytic oxidation. 

PMID- 25994310
TI  - Predictors of students' self-reported adoption of a smartphone application for
      medical education in general practice.
AB  - BACKGROUND: Smartphones and related applications are increasingly gaining
      relevance in the healthcare domain. We previously assessed the demands and
      preferences of medical students towards an application accompanying them during a
      course on general practice. The current study aims to elucidate the factors
      associated with adoption of such a technology. Therefore we provided students
      with a prototype of an application specifically related to their studies in
      general practice. METHODS: A total estimation among students participating in a
      general practice examination at the Leipzig Medical School was conducted in May
      2014. Students were asked to answer a structured self-designed questionnaire.
      Univariable comparisons were made to identify significant differences between
      those students who reported to have used the application frequently and those who
      did not. Multivariable binary logistic regression was used to reveal independent
      predictors of frequent application usage. RESULTS: The response rate was 99.3 %
      (n = 305/307). The majority (59 %, n = 180/305) were female students. The mean
      age was 24.5 years and 79.9 % (n = 243/304) owned a smartphone or tablet
      computer. Regarding the usage of the provided application, 2.3 % (n = 7/303) did
      not use the app while 68.0 % (n = 206/303) replied to have used it more than five
      times. Frequent users significantly differed from non-frequent users with regard
      to being female rather than male, higher mobile device ownership, more frequent
      exchange about obtaining the course certificate, higher personal interest in new
      technologies, larger enjoyment of the technology, lower intention to not use
      smartphone applications in the future, better opinion towards smartphone
      applications for the profession of a doctor, higher perceived importance of
      medical applications on the job, higher compatibility of smartphone applications
      with personal work style, higher perceived relevance of university support and
      personal benefit of use. Multivariable analysis revealed a set of four variables
      independently predicting frequent usage: being female, a higher perceived benefit
      of the supplied application, a higher personal interest in new technologies, and
      a higher perceived impact of previous experiences on smartphone adoption (Pseudo
      R(2)(Nagelkerke) = 0.245). CONCLUSIONS: Understanding medical students' adoption
      of smartphone applications used for educational purposes may provide useful
      information to guide the implementation process as well as the design of
      respective applications.

PMID- 25994312
TI  - Liver sinusoid on a chip: Long-term layered co-culture of primary rat hepatocytes
      and endothelial cells in microfluidic platforms.
AB  - We describe the generation of microfluidic platforms for the co-culture of
      primary hepatocytes and endothelial cells; these platforms mimic the architecture
      of a liver sinusoid. This paper describes a progressional study of creating such
      a liver sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co
      cultured with primary or established endothelial cells in layers in single and
      dual microchannel configurations with or without continuous perfusion. Cell
      viability and maintenance of hepatocyte functions were monitored and compared for
      diverse experimental conditions. When primary rat hepatocytes were co-cultured
      with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel
      with continuous perfusion, hepatocytes maintained their normal morphology and
      continued to produce urea for at least 30 days. In order to demonstrate the
      utility of our microfluidic liver sinusoid platform, we also performed an
      analysis of viral replication for the hepatotropic hepatitis B virus (HBV). HBV
      replication, as measured by the presence of cell-secreted HBV DNA, was
      successfully detected. We believe that our liver model closely mimics the in vivo
      liver sinusoid and supports long-term primary liver cell culture. This liver
      model could be extended to diverse liver biology studies and liver-related
      disease research such as drug induced liver toxicology, cancer research, and
      analysis of pathological effects and replication strategies of various
      hepatotropic infectious agents. .

PMID- 25994313
TI  - Protective immunity against Eimeria tenella infection in chickens following oral
      immunization with Bacillus subtilis expressing Eimeria tenella 3-1E protein.
AB  - The current experiment was conducted to construct recombinant Bacillus subtilis
      WB600 expressing Eimeria tenella 3-1E protein to investigate the oral
      immunization protective effects against E. tenella. The merozoite surface antigen
      3-1E gene of E. tenella was introduced into the pBS-H1 expression vector with a
      novel signal peptide sequence. After the electro-transformation, the expression
      of objective protein in B. subtilis WB600 was detected by Western blot. The
      results showed that the recombinant B. subtilis strain with the ability of high
      level secretion of 3-1E was constructed successfully. Seven-day-old broiler
      chickens were orally vaccinated with B. subtilis WB600 harboring 3-1E (B.S-pBS-H1
      3-1E) or B. subtilis WB600 with empty plasmid (B.S-pBS-H1) 10 days prior to
      challenge with sporulated E. tenella oocysts. The results showed the recombinant
      B. subtilis strain with the ability of high-level secretion of 3-1E was
      constructed successfully. Vaccination with B.S-pBS-H1-3-1E strain significantly
      increased the anti-coccidial index and reduced cecal lesion scores compared with
      the positive control group (chickens were challenged with sporulated E. tenella
      oocysts without oral administration of B.S-pBS-H1-3-1E strain) and B.S-pBS-H1
      group. Ceca mucosal sIgA, secretion, and IL-2, IL-12, IFN-gamma, and IL-10 level
      after challenge were greater in the B.S-pBS-H1-3-1E group than in the positive
      control group. Taken together, these results indicated that B. subtilis WB600
      harboring 3-1E protein induces protective immunity against E. tenella.

PMID- 25994314
TI  - Features of Blastocystis spp. in xenic culture revealed by deconvolutional
      microscopy.
AB  - Blastocystis spp. are common human enteric parasites with complex morphology and
      have been reported to cause irritable bowel syndrome (IBS). Deconvolutional
      microscopy with time-lapse imaging and fluorescent spectroscopy of xenic cultures
      of Blastocystis spp. from stool samples of IBS patients and from asymptomatic,
      healthy pigs allowed observations of living organisms in their natural microbial
      environment. Blastocystis organisms of the vacuolated, granular, amoebic and
      cystic forms were observed to autofluorescence in the 557/576 emission spectra.
      Autofluorescence could be distinguished from fluorescein-conjugated Blastocystis
      specific antibody labelling in vacuolated and granular forms. This antibody
      labelled Blastocystis subtypes 1, 3 and 4 but not 5. Surface pores of 1 MUm in
      diameter were observed cyclically opening and closing over 24 h. Vacuolated forms
      extruded a viscous material from a single surface point with coincident deflation
      that may demonstrate osmoregulation. Tear-shaped granules were observed exiting
      from the surface of an amoebic form, but their origin and identity remain
      unknown.

PMID- 25994315
TI  - Investigating the in vitro stereoselective metabolism of m-nisoldipine
      enantiomers: characterization of metabolites and cytochrome P450 isoforms
      involved.
AB  - m-Nisoldipine, as a novel 1,4-dihydropyridine calcium ion antagonist, was
      presented as a couple of enantiomers [(-), (+)-m-nisoldipine]. In this report,
      the in vitro metabolism of m-nisoldipine enantiomers was investigated in rat
      liver microsomes (RLM) by the combination of two liquid chromatography mass
      spectrometric techniques for the first time. The metabolites were separated and
      assayed by ultra-high performance liquid chromatography coupled to quadrupole
      time-of-flight mass spectrometry and further identified by comparison of their
      mass and chromatographic behaviors with reference substances. A total of 18
      metabolites of (-)-m-nisoldipine and 16 metabolites of (+)-m-nisoldipine were
      detected, respectively, which demonstrated that (+)-m-nisoldipine is more
      metabolically stable than (-)-m-nisoldipine. In addition, the identified
      metabolic pathways of m-nisoldipine enantiomers were involved in dehydrogenation,
      oxidation and ester hydrolysis. Afterwards, based on high-performance liquid
      chromatography coupled to triple quadrupole linear ion trap mass spectrometry,
      various selective cytochrome P450 (CYP) enzyme inhibitors were employed to
      evaluate CYP isoforms. The results indicated that the inhibitors of CYP1A1/2,
      CYP2B1/2, 2D and 2C11 had no obvious inhibitory effects, yet the inhibitor of CYP
      3A had a significant inhibitory effect on metabolism of m-nisoldipine
      enantiomers. This showed that CYP 3A might primarily metabolize m-nisoldipine in
      RLM.

PMID- 25994316
TI  - What is the evidence for postoperative lumbar drains in endoscopic repair of CSF
      leaks?

PMID- 25994317
TI  - Through the years with on-a-chip gas chromatography: a review.
AB  - In recent years, the need for measurement and detection of samples in situ or
      with very small volume and low concentration (low and sub-parts per billion) is a
      cause for miniaturizing systems via microelectromechanical system (MEMS)
      technology. Gas chromatography (GC) is a common technique that is widely used for
      separating and measuring semi-volatile and volatile compounds. Conventional GCs
      are bulky and cannot be used for in situ analysis, hence in the past decades many
      studies have been reported with the aim of designing and developing chip-based
      GC. The focus of this review is to follow and investigate the development and the
      achievements in the field of chip-based GC and its components from the beginning
      up to the present. 

PMID- 25994318
TI  - Providing Palliative Care in a Swedish Support Home for People Who Are Homeless.
AB  - Despite high frequencies of multiple, life-limiting conditions relating to
      palliative care needs, people who are homeless are one of the most underserved
      and rarely encountered groups in palliative care settings. Instead, they often
      die in care places where palliative competence is not available. In this
      qualitative single-case study, we explored the conditions and practices of
      palliative care from the perspective of staff at a Swedish support home for
      homeless people. Interpretive description guided the research process, and data
      were generated from repeated reflective conversations with staff in groups,
      individually, and in pairs. The findings disclose a person-centered approach to
      palliative care, grounded in the understanding of the person's health/illness and
      health literacy, and how this is related to and determinant on life as a homeless
      individual. Four patterns shape this approach: building trustful and family-like
      relationships, re-dignifying the person, re-considering communication about
      illness and dying, and re-defining flexible and pragmatic care solutions.

PMID- 25994320
TI  - Associations Between Parental Health Literacy, Use of Asthma Management Plans,
      and Child's Asthma Control.
AB  - BACKGROUND: There are some studies demonstrating the effectiveness of the
      provision of written asthma action plans in improving asthma outcomes. There
      exist little data on the ability of parents to use these plans to make asthma
      care decisions. OBJECTIVE: To assess the associations between parental health
      literacy (HL), parental ability to use a written asthma management plan (WAMP),
      and child's asthma control. METHODS: Parents completed a survey with questions
      related to WAMPs and child's asthma, a HL screening tool, and 5 asthma vignettes.
      For vignettes, parents identified asthma control zone and then made decisions
      about asthma management. WAMP scores were totaled (0-32) and converted to a
      percent correct score. Associations between parental HL, WAMP scores, child's
      asthma control, and demographics were determined with independent t tests or 1
      way analysis of variance, and chi-square tests. Variables significantly
      associated with WAMP scores or asthma control were included in multiple logistic
      regression or multiple linear regression analyses. RESULTS: A total of 176
      surveys were included; the mean +/- SD WAMP score was 58.9% +/- 22.2%, and 25% of
      respondents had limited HL. Of respondents' children, 38% had not well/poorly
      controlled asthma. In multiple regression analysis controlling for education
      level, limited HL was significantly associated with WAMP score (b = 11.3,
      standard error 3.8, P = .004). WAMP score was not associated with asthma control.
      Limited HL was associated with poor asthma control in univariate analysis, but
      not in a logistic regression model controlling for other significant variables.
      Only unmarried marital status (adjusted odds ratio 4.4, 95% CI 1.8-10.8, P =
      .001) was associated with asthma control. CONCLUSION: HL is associated with
      parental ability to use WAMPs to respond to asthma scenarios. Parental HL may
      play a role in parents' ability to appropriately use WAMPs.

PMID- 25994319
TI  - Narrowing Care Gaps for Early Language Delay: A Quality Improvement Study.
AB  - BACKGROUND AND OBJECTIVE: Poverty is a risk factor for both language delay and
      failure to access appropriate therapies. The objective of this study was to
      increase the percentage of children 0 to 3 years old referred from an urban
      primary care center who attended an initial appointment with speech pathology or
      audiology within 60 days from 40% to 60%. METHODS: The Model for Improvement was
      used to develop and test the intervention, which addressed potential logistical
      barriers faced by low-income families. Adherence was plotted on run charts in
      time series to assess overall improvement, and subgroups were analyzed to
      identify reduction in disparities. RESULTS: Median referral adherence improved
      from 40% to 60%. Families from lower income neighborhoods had lower
      preintervention adherence; these differences were eliminated postintervention.
      CONCLUSIONS: System-level changes improved access to evaluation and treatment for
      low-income children with language delay and narrowed the gap in access between
      families in lower versus higher income neighborhoods.

PMID- 25994321
TI  - Evaluating a 12-week exercise program for brain cancer patients.

PMID- 25994322
TI  - Challenges in managing patients who have suspected or confirmed Ebola virus
      infection at the National Institutes of Health.

PMID- 25994323
TI  - Lessons learned from hospital Ebola preparation.
AB  - BACKGROUND: Hospital Ebola preparation is underway in the United States and other
      countries; however, the best approach and resources involved are unknown.
      OBJECTIVE: To examine costs and challenges associated with hospital Ebola
      preparation by means of a survey of Society for Healthcare Epidemiology of
      America (SHEA) members. DESIGN: Electronic survey of infection prevention
      experts. RESULTS: A total of 257 members completed the survey (221 US, 36
      international) representing institutions in 41 US states, the District of
      Columbia, and 18 countries. The 221 US respondents represented 158 (43.1%) of 367
      major medical centers that have SHEA members and included 21 (60%) of 35
      institutions recently defined by the US Centers for Disease Control and
      Prevention as Ebola virus disease treatment centers. From October 13 through
      October 19, 2014, Ebola consumed 80% of hospital epidemiology time and only 30%
      of routine infection prevention activities were completed. Routine care was
      delayed in 27% of hospitals evaluating patients for Ebola. LIMITATIONS:
      Convenience sample of SHEA members with a moderate response rate. CONCLUSIONS:
      Hospital Ebola preparations required extraordinary resources, which were diverted
      from routine infection prevention activities. Patients being evaluated for Ebola
      faced delays and potential limitations in management of other diseases that are
      more common in travelers returning from West Africa.

PMID- 25994324
TI  - Ebola as a test for emerging pathogen preparedness: the critical role of health
      systems in ensuring support.

PMID- 25994325
TI  - ERCP scopes: what can we do to prevent infections?

PMID- 25994326
TI  - Decreasing trends of healthcare-associated infections: multifactorial synergy.

PMID- 25994327
TI  - Adopting a global safety standard for the prevention of Ebola needle-stick
      exposures.

PMID- 25994328
TI  - Taxonomy in the age of genomics. Introduction.

PMID- 25994329
TI  - Intramolecular B/N frustrated Lewis pairs and the hydrogenation of carbon
      dioxide.
AB  - The FLP species 1-BR2-2-NMe2-C6H4 (R = 2,4,6-Me3C6H2, 2,4,5-Me3C6H2) reacts with
      H2 in sequential hydrogen activation and protodeborylation reactions to give (1
      BH2-2-NMe2-C6H4)2. While reacts with H2/CO2 to give formyl, acetal and methoxy
      derivatives, reacts with H2/CO2 to give C6H4(NMe2)(B(2,4,5-Me3C6H2)O)2CH2. The
      mechanism of CO2 reduction is considered. 

PMID- 25994330
TI  - Molecular characterization of Cryptosporidium spp. and Giardia duodenalis from
      yaks in the central western region of China.
AB  - BACKGROUND: Cryptosporidium spp. and Giardia duodenalis are important causes of
      diarrheal diseases in humans and animals worldwide, and there is an increased
      interest in the role of animals in the mechanical transmission of these protozoa.
      To examine the role of yaks in this process, we examined the occurrence and
      genotypes of Cryptosporidium and G. duodenalis in yaks in western China. RESULTS:
      A total of 545 fecal specimens were collected from yaks from nine different
      counties in the central western region of China. The prevalence for
      Cryptosporidium spp. and G. duodenalis were 4.0 % (22/545) and 6.0 % (16/545),
      respectively. Mixed infections of Cryptosporidium and G. duodenalis were also
      detected in four specimens. The prevalence of both protozoa differed
      significantly between some age groups, with higher rates of infection in animals
      < 1 year old. Sequence analysis of the small subunit rRNA (SSU rRNA) gene of the
      Cryptosporidium isolates identified the species as C. parvum (n = 12), C. bovis
      (n = 6), C. ryanae (n = 3), and C. ubiquitum (n = 1). Genotyping based on 60-kDa
      glycoprotein (gp60) gene from five C. parvum isolates identified all as IId with
      three isolates identified as IIdA15G1, one as IIdA18G1, and one as IIdA19G1. One
      C. ubiquitum isolate was identified as subtype VIIa. Amongst the G. duodenalis
      isolates, 16 were identified as assemblage E at the SSU rRNA gene. Four novel
      glutamate dehydrogenase (gdh) subtypes and two triosephosphate isomerase (tpi)
      subtypes were found amongst the G. duodenalis assemblage E isolates. CONCLUSIONS:
      The presence of C. parvum subtype IIdA15G1, IIdA18G1, and IIdA19G1 isolates
      further confirms the dominance of the C. parvum IId subtypes in China. These
      findings also indicate that yaks may be a source of zoonotic Cryptosporidium
      infection, and this is the first report of G. duodenalis in yaks. The data
      presented here provides the basis for further genotyping or subtyping studies of
      G. duodenalis in yaks.

PMID- 25994332
TI  - Delta10(E)-Sphingolipid Desaturase Involved in Fusaruside Mycosynthesis and
      Stress Adaptation in Fusarium graminearum.
AB  - Sphingolipids are biologically important and structurally distinct cell membrane
      components. Fusaruside (1) is a 10,11-unsaturated immunosuppressive fungal
      sphingolipid with medical potentials for treating liver injury and colitis, but
      its poor natural abundance bottlenecks its druggability. Here, fusaruside is
      clarified biosynthetically, and its efficacy-related 10,11-double bond can be
      generated under the regioselective catalysis of an unprecedented Delta10(E)
      sphingolipid desaturase (Delta10(E)-SD). Delta10(E)-SD shares 17.7% amino acid
      sequence similarity with a C9-unmethylated Delta10-sphingolipid desaturase
      derived from a marine diatom, and 55.7% with Delta8(E)-SD from Fusarium
      graminearum. Heterologous expression of Delta10(E)-SD in Pichia pastoris has been
      established to facilitate a reliable generation of 1 through the Delta10(E)-SD
      catalyzed desaturation of cerebroside B (2), an abundant fungal sphingolipid.
      Site directed mutageneses show that the conserved histidines of Delta10(E)-SD are
      essential for the 10,11-desaturation catalysis, which is also preconditioned by
      the C9-methylation of the substrate. Moreover, Delta10(E)-SD confers improved
      survival and faster growth to fungal strains at low temperature and high
      salinity, in parallel with to higher contents of 1 in the mycelia. Collectively,
      the investigation describes a new Delta10(E)-sphingolipid desaturase with its
      heterologous expression fundamentalizing a biotechnological supply of 1, and
      eases the follow-up clarification of the immunosuppression and stress-tolerance
      mechanism. 

PMID- 25994333
TI  - Multi-eigenmode control for high material contrast in bimodal and higher harmonic
      atomic force microscopy.
AB  - High speed imaging and mapping of nanomechanical properties in atomic force
      microscopy (AFM) allows the observation and characterization of dynamic sample
      processes. Recent developments involve several cantilever frequencies in a
      multifrequency approach. One method actuates the first eigenmode for topography
      imaging and records the excited higher harmonics to map nanomechanical properties
      of the sample. To enhance the higher frequencies' response two or more eigenmodes
      are actuated simultaneously, where the higher eigenmode(s) are used to quantify
      the nanomechanics. In this paper, we combine each imaging methodology with a
      novel control approach. It modifies the Q factor and resonance frequency of each
      eigenmode independently to enhance the force sensitivity and imaging bandwidth.
      It allows us to satisfy the different requirements for the first and higher
      eigenmode. The presented compensator is compatible with existing AFMs and can be
      simply attached with minimal modifications. Different samples are used to
      demonstrate the improvement in nanomechanical contrast mapping and imaging speed
      of tapping mode AFM in air. The experiments indicate most enhanced nanomechanical
      contrast with low Q factors of the first and high Q factors of the higher
      eigenmode. In this scenario, the cantilever topography imaging rate can also be
      easily improved by a factor of 10. 

PMID- 25994331
TI  - World Workshop on Oral Medicine VI: a systematic review of medication-induced
      salivary gland dysfunction: prevalence, diagnosis, and treatment.
AB  - OBJECTIVES: Medication-induced salivary gland dysfunction (MISGD) causes
      significant morbidity resulting in decreased quality of life. This systematic
      review assessed the literature on the prevalence, diagnosis, treatment, and
      prevention of MISGD. MATERIALS AND METHODS: Electronic databases were searched
      for articles related to MISGD through June 2013. Four independent reviewers
      extracted information regarding study design, study population, interventions,
      outcomes, and conclusions for each article. Only papers with acceptable degree of
      relevance, quality of methodology, and strength of evidence were retained for
      further analysis. RESULTS: There were limited data on the epidemiology of MISGD.
      Furthermore, various methods were used to assess salivary flow rate or
      xerostomia. Preventive and therapeutic strategies included substitution of
      medications, oral, or systemic therapy with sialogogues, use of saliva
      substitutes or of electro-stimulating devices. Although there are promising
      approaches to improve salivary gland function, most studies are characterized by
      small numbers and heterogeneous methods. CONCLUSIONS: Physicians and dentists
      should identify the medications associated with xerostomia and salivary gland
      dysfunction through a thorough medical history. Preferably, health care providers
      should measure the unstimulated and stimulated whole salivary flow rates of all
      their patients so that these values can be used as a baseline to rate the
      complaints of patients who subsequently claim to experience xerostomia or
      salivary gland dysfunction as well as the possibilities of effectively treating
      this condition. CLINICAL RELEVANCE: MISGD remains a major burden for the
      population. This systematic review provides a contemporary in-depth description
      of the diagnosis and treatment of MISGD.

PMID- 25994334
TI  - Evaluation of disease burden and response to treatment in adults with type 1
      Gaucher disease using a validated disease severity scoring system (DS3).
AB  - BACKGROUND: GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1)
      burden based on bone, hematologic and visceral domains. We investigated this
      disease severity scoring system (DS3) methodology for initial assessment, long
      term follow-up and evaluation of treatment responses. METHODS: We enrolled 133
      treated adult GD1 patients. Baseline DS3 scores were calculated near the initial
      treatment date and patients stratified by severity as marked (DS3 6.00-19.00),
      moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated
      annually. Minimal clinically important improvement (MCII), is defined as DeltaDS3
      of -3.1. RESULTS:  PATIENT CHARACTERISTICS: N370S was the most common allele (118
      patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews),
      N370S/L444P was the most common genotype among non-Jews. Median age of treatment:
      45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked
      disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and
      most likely to have had splenectomy (53 %), early age at diagnosis (median 18
      years) and major pre-treatment bone pathology (76 %). Among patients with
      moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had
      splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years.
      No patient with mild disease (N = 22; median 2.4) had splenectomy or major
      skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous.
      Response to treatment: Health-state transitions occurred primarily during the
      early treatment years. At Year 5, among 48 evaluable patients with marked
      baseline disease, eight were unchanged in severity status whereas 40 had MCII of
      varying degrees with 11 scored as mild. Among 42 evaluable moderate patients,
      none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable
      mild patients, 14 remained so and 2 had DS3 scores in the low moderate range.
      CONCLUSIONS: DS3 is effective for assessing disease burden in GD1 and for
      monitoring response. ERT was associated with MCII in DS3 scores in patients with
      high severity. Nevertheless, despite better DS3 scores with treatment, GD1
      patients especially those with splenectomy and pre-treatment bone pathology,
      continued to have bone complications.

PMID- 25994335
TI  - Traditional posterior load carriage: effects of load mass and size on torso
      kinematics, kinetics, muscle activity and movement stability.
AB  - Traditional posterior load carriage (PLC), done without the use of an assistive
      device (e.g., backpack), has been associated with low back pain (LBP)
      development. This study evaluated the effects of important task demands, related
      to load mass and size, on potential mechanisms linking traditional PLC with LBP.
      Nine healthy participants completed PLC tasks with three load masses (20%, 35%
      and 50% of individual body mass) and three load sizes (small, medium and large).
      Torso kinematics, kinetics, muscle activity and slip risk were evaluated during
      PLC on a walkway, and torso movement stability was quantified during PLC on a
      treadmill. Increasing load mass caused increased torso flexion, L5/S1 flexion
      moment, abdominal muscle activity and torso movement stability in the frontal
      plane. Increasing load size also caused higher torso flexion, peak torso angular
      velocity and acceleration, and abdominal muscle activity. Complex interactive
      effects of load mass and size were found on paraspinal muscle activity and slip
      risk. Specific task demands, related to load mass and size, may thus influence
      the risk of LBP during PLC. PRACTITIONER SUMMARY: This study examined the effects
      of load mass and size on low back pain (LBP) risk using intermediary measures
      derived from torso kinematics, kinetics and muscle activity. Our current
      findings, along with earlier work, suggest that load mass and size can influence
      LBP risk, and that use of smaller and light loads may be beneficial during PLC.

PMID- 25994337
TI  - Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index:
      characterizing disease severity and assessing responsiveness to clinical change.
AB  - BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
      was developed for use in clinical trials and longitudinal patient assessment.
      OBJECTIVES: To characterize disease severity using the CDASI and assess the
      responsiveness of this instrument to clinically meaningful changes in disease
      activity. METHODS: Patients with cutaneous dermatomyositis at the University of
      Pennsylvania (UPenn, n = 93) and Stanford University (Stanford, n = 106) were
      prospectively evaluated using the CDASI, physician global assessment (PGA) Likert
      scales and a visual analogue scale (VAS). Data was analysed using logistic
      regression models and receiver operating characteristic curves to select cut
      offs. RESULTS: Baseline CDASI activity scores for the patients evaluated at UPenn
      ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9.6
      (median 1.1). At UPenn a CDASI activity score of 19 differentiated mild from
      moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to
      48 (median 21), baseline PGA VAS scores ranged from 0 to 9.7 (median 4.2) and
      CDASI activity scores of 14 or less characterized mild disease. When a 2-cm
      change in the PGA VAS was regarded as a clinically significant improvement, a 4
      point (UPenn) or 5-point (Stanford) change in CDASI reflected a minimal
      clinically significant response. CONCLUSIONS: The CDASI is a valid and responsive
      measure that can be used to characterize cutaneous dermatomyositis severity and
      detect improvement in disease activity. Variations in cut-offs may be due to
      differences in disease severity between the two populations or inter-rater
      variations in the use of the external gold measures.

PMID- 25994339
TI  - [Analysis of Environmental-Stress-Related Impairments of Inner Ear].
AB  - Noise stress generated in industry is one of the environmental factors that
      physically affects the functions of the inner ear. Exposure to noise can cause
      hearing loss, resulting in serious problems in occupational and daily life. At
      present, however, there are very limited ways to prevent hearing impairments. The
      inner ear consists of the organ of Corti, vestibule and semicircular canal.
      Functional or morphological damage of these tissues in the inner ear caused by
      genetic factors, aging or environmental factors can result in hearing or balance
      impairments. In this review, we first introduce a deafness-related molecule found
      by our clinical research. Our experimental research using genetically engineered
      mice further demonstrated that impaired activity of the target molecule caused
      congenital and age-related hearing loss with neurodegeneration of spiral ganglion
      neurons in the inner ears. We also describe impaired balance in mice caused by
      exposure to low-frequency noise under experimental conditions with indoor
      environmental monitoring. We believe that our approaches to pursue both
      experimental research and fieldwork research complementarily are crucial for the
      development of a method for prevention of impairments of the inner ear.

PMID- 25994340
TI  - [Analysis of heavy-metal-mediated disease and development of a novel remediation
      system based on fieldwork and experimental research].
AB  - Heavy-metal pollution occurs in various environments, including water, air and
      soil, and has serious effects on human health. Since heavy-metal pollution in
      drinking water causes various diseases including skin cancer, it has become a
      global problem worldwide. However, there is limited information on the mechanism
      of development of heavy-metal-mediated disease. We performed both fieldwork and
      experimental studies to elucidate the levels of heavy-metal pollution and
      mechanisms of development of heavy-metal-related disease and to develop a novel
      remediation system. Our fieldwork in Bangladesh, Vietnam and Malaysia
      demonstrated that drinking well water in these countries was polluted with high
      concentrations of several heavy metals including arsenic, barium, iron and
      manganese. Our experimental studies based on the data from our fieldwork
      demonstrated that these heavy metals caused skin cancer and hearing loss. Further
      experimental studies resulted in the development of a novel remediation system
      with which toxic heavy metals were absorbed from polluted drinking water.
      Implementation of both fieldwork and experimental studies is important for
      prediction, prevention and therapy of heavy-metal-mediated diseases. 

PMID- 25994336
TI  - Major histocompatibility complex associations of ankylosing spondylitis are
      complex and involve further epistasis with ERAP1.
AB  - Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis
      for which HLA-B*27 is the major genetic risk factor, although its role in the
      aetiology of AS remains elusive. To better understand the genetic basis of the
      MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and
      controls of European descent. We impute SNPs, classical HLA alleles and amino
      acid residues within HLA proteins, and tested these for association to AS status.
      Here we show that in addition to effects due to HLA-B*27 alleles, several other
      HLA-B alleles also affect susceptibility. After controlling for the associated
      haplotypes in HLA-B, we observe independent associations with variants in the HLA
      A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187
      association is not restricted only to carriers of HLA-B*27 but also found in HLA
      B*40:01 carriers independently of HLA-B*27 genotype. 

PMID- 25994341
TI  - [Experimental Approach to Analysis of the Relationship between Food Environments
      and Lifestyle-Related Diseases, Including Cardiac Hypertrophy, Fatty Liver, and
      Fatigue Symptoms].
AB  - The food habit is involved in the onset and development of lifestyle-related
      diseases. In this review I would like to describe a historical case of vitamin B1
      deficiency, as well as our case study of fatty acid metabolism abnormality due to
      carnitine deficiency. In history, the army and navy personnel in Japan at the end
      of the 19th century received food rations based on a high-carbohydrate diet
      including white rice, resulting in the onset of beriberi. An epidemiological
      study by Kenkan Takaki revealed the relationship between the onset of beriberi
      and rice intake. Then, Takaki was successful in preventing the onset of beriberi
      by changing the diet. However, the primary cause had yet to be elucidated.
      Finally, Christian Eijkman established an animal model of beriberi (chickens)
      showing peripheral neuropathy, and he identified the existence of an anti
      beriberi substance, vitamin B1. This is an example of the successful control of a
      disease by integrating the results of epidemiological and experimental studies.
      In our study using a murine model of fatty acid metabolism abnormality caused by
      carnitine deficiency, cardiac abnormality and fatty liver developed depending on
      the amount of dietary fat. In addition, the mice showed disturbance of orexin
      neuron activity related to the sleep-arousal system, which is involved in fatigue
      symptoms under fasting condition, one of the states showing enhanced fatty acid
      metabolism. These findings suggest that fatty acid toxicity is enhanced when the
      mice are more dependent on fatty acid metabolism. Almost simultaneously, a human
      epidemiological study showed that narcolepsy, which is caused by orexin system
      abnormality, is associated with the polymorphism of the gene coding for carnitine
      palmitoyltransferase 1B, which is involved in carnitine metabolism. To understand
      the pathological mechanism of fatty acid toxicity, not only an experimental
      approach using animal models, but also an epidemiological approach is necessary.
      The results will be applied to preventing and treating lifestyle-related diseases
      associated with fatty acid metabolism abnormality. 

PMID- 25994342
TI  - [Immune System Reaction against Environmental Pollutants].
AB  - Environmental pollutants (such as diesel exhaust particles and silica) cause
      disorders ranging from bronchial asthma to malignant tumors. In recent years, it
      has been reported that some of the signaling pathways in which environmental
      contaminants act in vivo are associated with innate immunity. Innate immunity
      recognizes ligands and induces inflammation. Those ligands are pathogen
      associated molecular patterns (PAMPs: e.g., lipopolysaccharide) and danger
      associated molecular patterns (DAMPs: e.g., cholesterol crystallization or uric
      acid crystal). Activation of innate immunity stimulates the acquired immunity
      system. Therefore, innate immunity regulates the strength of the general immune
      system. Furthermore, crystal silica, which is an environmental pollutant,
      activates innate immunity as a ligand. Innate immunity involves the membrane
      bound Toll-like receptors (TLR) and cytoplasm-localized nucleotide-binding
      oligomerization domain (NOD)-like receptors (NLR). We reported the innate
      immunity-system-related diseases such as Crohn's disease, Blau syndrome,
      myelogenous leukemia, and sarcoidosis. An inflammasome complex containing NLR has
      attracted attention owing to its correlation with the onset of several diseases.
      It is reported that the inflammasome activation is related to the development of
      lifestyle-related diseases such as myocardial infarction and fatty liver. It is
      also reported that the mechanism by which crystal silica and asbestos cause
      inflammation involves the inflammasome activation. Analyzing the genes of innate
      immunity contributes to the clarification of the mechanism of disease onset
      caused by environmental pollutants. 

PMID- 25994343
TI  - [Development of Higher Brain Function Tests in Rodents and Its Application to
      Neurotoxicity Assessment of Environmental Chemicals].
AB  - The brain during developmental period is thought to be highly sensitive to
      environmental insults including exposure to chemicals. However, it has been
      extremely difficult to detect and assess the features and degree of adversity
      particularly at low exposure levels. I describe here the effects of maternal
      exposure to dioxin on higher brain functions later in life, which we detected
      using our originally developed behavioral tests for quantifying higher brain
      functions in rodents. We first found changes in the mRNA expression levels of
      glutamate NMDA receptor subunits that have critical roles in learning and memory
      function in the neocortex and hippocampus. To assess the neocortical and
      hippocampal functions in rats, we established novel behavioral tests for
      assessing paired-associate learning, which is the hippocampal and medial
      prefrontal NMDA-dependent function. Maternal exposure to dioxin, at a low level
      of which does not affect simple memory formation, resulted in the disturbance of
      the paired-associate learning. On the basis of the above learning paradigm, we
      next developed a behavioral flexibility task and a social competitive task for
      mice using the automated behavioral assessment system 'IntelliCage': this system
      can accommodate 16 mice at the same time to monitor and record their behavior.
      Using this system, we found that male mice born to dams exposed to very low doses
      of dioxin showed inflexibility in a serial reversal learning task and socially
      low-dominance behavior under a competitive situation. Immunohistochemical
      analysis of putative neuronal activity markers revealed hypoactivity in the
      medial prefrontal cortex (mPFC) of dioxin-exposed mice. We speculate that mPFC
      hypoactivity reflects the dioxin-induced higher brain dysfunction and may be
      associated with some psychiatric illnesses and related problems. These behavioral
      tests were found to be useful for studying the higher brain functions of rats and
      mice.

PMID- 25994344
TI  - [Oxidative stress derived from airborne fine and ultrafine particles and the
      effects on brain-nervous system: part 1].
AB  - Traffic-related air pollution is a major contributor to urban air pollution.
      Diesel exhaust (DE) is the most important component of near-road and urban air
      pollution and is commonly used as a surrogate model of air pollution in health
      effects studies. In particular, diesel exhaust particles (DEP) and the
      nanoparticles in DEP are considered hazardous components on health effects. It is
      widely known that exposure to DEP is associated with mortality due to respiratory
      and cardiovascular diseases. Recently, there has been accumulating evidence that
      DEP and the nanoparticles in DEP may be causes of neurodegenerative disorders.
      Here, we introduce the evidence suggesting their association with such disorders.
      First, we describe the chemical components and the translocation of DEP and
      nanoparticles to the brain, and then introduce the evidence and a mechanism by
      which reactive oxygen species (ROS) and any inflammatory mediators can be
      produced by DEP phagocytosis of macrophages, microglia and astrocyte cells in the
      brain. There are many lines of evidence showing that the neurodegenerative
      disorders are profoundly associated with enhanced oxidative and inflammatory
      events. Second, we describe a mechanism by which neurodegenerative diseases, such
      as stroke, Alzheimer's disease and Parkinson's disease, are induced via oxidative
      stress and inflammatory events. 

PMID- 25994345
TI  - [Associations between ALDH2 and ADH1B Genotypes and Ethanol-Induced Cutaneous
      Erythema in Young Japanese Women].
AB  - OBJECTIVES: The purpose of this study was to identify associations between ALDH2
      and ADH1B genotypes and ethanol-induced cutaneous erythema and assess the
      accuracy of an ethanol patch test in young Japanese women. METHODS: The subjects
      were 942 female Japanese university students. They were given an ethanol patch
      test and examined for ethanol-induced cutaneous erythema both immediately after
      removing the patch and 10 minutes after removing the patch. A saliva sample was
      used to determine the ALDH2 and ADH1B genotype of each subject by realtime PCR.
      RESULTS: The sensitivity and specificity of erythema immediately after removing
      the patch as the marker for the presence of inactive ALDH2 were 69.6% and 87.7%,
      respectively, and the sensitivity and specificity of erythema 10 minutes after
      removing the patch were 85.2% and 85.1%, respectively. The sensitivity of
      erythema after 10 minutes was markedly lower in the ADH1B*1/*1 carriers than in
      the ADH1B*2 carriers (8.3% vs. 89.7%, p<0.0001), and the specificity was
      significantly higher in the ADH1B*1/*1 carriers than in the ADH1B*2 carriers
      (96.9% vs. 84.3%, p<0.05). CONCLUSIONS: Overall, both sensitivity and specificity
      were satisfactorily high, but having the ADH1B*1/*1 genotype prevented a positive
      reaction for inactive ALDH2 and caused false-negative results. The data also
      suggested that having the ADH1B*2/*2 genotype caused a positive reaction in
      subjects with the ALDH2*1/*1 genotype. Despite these exceptions, the ethanol
      patch test has enough accuracy and can be used easily to subjects who don't drink
      alcohol. This is a valuable tool for improving the health literacy of younger
      generation subjects.

PMID- 25994346
TI  - [Menstrual cycle length and source of its variation in female university students
      majoring in nursing sciences].
AB  - OBJECTIVES: To acquire fundamental knowledge on menstrual cycle and its
      intraindividual variation in healthy Japanese female students and their
      association with biological attributes, lifestyle and food habit. METHODS: We
      asked female students of a nursing school to keep a diary of their menstruation
      over 5 consecutive months and to fill a questionnaire on their biological
      attributes, lifestyle and consumption frequency of some food items during the
      period from November 2012 to January 2014. RESULTS: The mean+/-standard deviation
      (SD) of cycle lengths of 180 women (20.4+/-0.9 yrs) was 34.2+/-10.5 days. Of
      these 180 women, 141 had a cycle length within the normal range (25-38 days)
      while 10 had a shorter cycle and 20 had a longer cycle. The intraindividual
      variations of the cycle, defined as "range" (difference between the longest and
      shortest cycles of an individual) and "SD" (SD of mean of multiple lengths within
      an individual), were 11.4+/-10.3 and 7.9+/-11.8 days, respectively. Of 177 women,
      73 and 109 had normal range and SD (<=6 days), respectively. The mean age of
      women with long cycles was older than that of women with short cycle (Kruscal
      Wallis test, p<0.05), and women with greater intraindividual variations were
      older than those with small variations (U-test, p<0.05). Subjects with menstrual
      pain had greater "SD" than did those without pain (Chi-square test, p<0.05).
      Neither lifestyle nor food habit was associated with the length and
      intraindividual variations of the menstrual cycle. CONCLUSIONS: The present
      results provided fundamental knowledge on the length and intraindividual
      variations of the menstrual cycle and the sources of these variations in female
      Japanese university students.

PMID- 25994347
TI  - [Measures against Radiation Exposure Due to Large-Scale Nuclear Accident in
      Distant Place--Radioactive Materials in Nagasaki from Fukushima Daiichi Nuclear
      Power Plant].
AB  - OBJECTIVE: To investigate human health effects of radiation exposure due to
      possible future nuclear accidents in distant places and other various findings of
      analysis of the radioactive materials contaminating the atmosphere of Nagasaki
      due to the Fukushima Daiichi Nuclear Power Plant accident. METHODS: The
      concentrations of radioactive materials in aerosols in the atmosphere of Nagasaki
      were measured using a germanium semiconductor detector from March 2011 to March
      2013. Internal exposure dose was calculated in accordance with ICRP Publ. 72. Air
      trajectories were analyzed using NOAA and METEX web-based systems. RESULTS:
      (134)Cs and (137)Cs were repeatedly detected. The air trajectory analysis showed
      that (134)Cs and (137)Cs flew directly from the Fukushima Daiichi Nuclear Power
      Plant from March to April 2011. However, the direct air trajectories were rarely
      detected after this period even when (134)Cs and (137)Cs were detected after this
      period. The activity ratios ((134)Cs/(137)Cs) of almost all the samples converted
      to those in March 2011 were about unity. This strongly suggests that the (134)Cs
      and (137)Cs detected mainly originated from the Fukushima Daiichi Nuclear Power
      Plant accident in March 2011. Although the (134)Cs and (137)Cs concentrations per
      air volume were very low and the human health effects of internal exposure via
      inhalation is expected to be negligible, the specific activities (concentrations
      per aerosol mass) were relatively high. CONCLUSION: It was found that possible
      future nuclear accidents may cause severe radioactive contaminations, which may
      require radiation exposure control of farm goods to more than 1000 km from places
      of nuclear accidents.

PMID- 25994348
TI  - [Psychological Effects of Forest Therapy Program on Workers].
AB  - OBJECTIVES: To examine the psychological effects of forest therapy program on
      workers. METHODS: The subjective symptoms index, a shortened version of the
      profile of mood states (POMS), and a semantic differential (SD) method were used
      to measure the psychological effects. RESULTS: The evaluations were performed 3
      days before, during, and 1, 3, and 5 days after the forest therapy. The following
      results were obtained: (1) the subjective symptoms improved before breakfast and
      continued for 5 days; (2) the mood evaluated using POMS improved before breakfast
      and continued for 3 days; and (3) "comfortable," "relaxed," and "natural"
      feelings evaluated using the SD method were enhanced before breakfast, lunch, and
      dinner during forest therapy. CONCLUSIONS: These results provided scientific
      evidence of the psychological effects of forest therapy program on workers.

PMID- 25994349
TI  - [Oral health status of pregnant women in Kumamoto Prefecture].
AB  - OBJECTIVES: As part of Kumamoto RAINBOW Project, which is a multifaceted
      implementation for the prevention of premature labor, we investigated pregnant
      women's oral health status and assessed the effects of dental care and oral
      hygiene instruction. METHODS: We examined the oral health status of pregnant
      women both in the first and the second half of pregnancy in Kumamoto Prefecture
      from 2012 to 2014. The Community Periodontal Index (CPI) was used to assess the
      periodontal condition, and women having periodontal pockets with a depth >=4 mm
      were defined as suffering from periodontitis. This project covered the cost of
      dental checkups. RESULTS: Of the 20,702 pregnant women enrolled in this project,
      9,527 (46.0%) received dental checkups during the first half of pregnancy. The
      response rate of dental examinations in Kumamoto City (63.3%), the capital city
      of Kumamoto Prefecture, was significantly higher than that of the other local
      areas (32.0%). In Kumamoto City, 4,890 women (83.4%) had dental examinations at
      the city office when they received a maternal handbook. Three thousand forty-five
      women (32.0%) had periodontitis. Among 1,605 women who received oral examinations
      twice at dental clinics, 698 received nonsurgical interventions. Dental
      interventions significantly decreased the prevalence of periodontitis in pregnant
      women (55.1% to 45.1%). Dental examinations without interventions also
      significantly decreased the prevalence of periodontitis (44.6% to 39.9%).
      CONCLUSIONS: Pregnant women living in Kumamoto City had higher rate of visits to
      dental clinics for checkups than those in other areas. Periodontitis was found in
      one-third of pregnant women. Not only dental interventions, but also dental
      examinations improve pregnant women's oral health status.

PMID- 25994352
TI  - Household environment and behavioral determinants of respiratory tract infection
      in infants and young children in northern Bangladesh.
AB  - OBJECTIVES: Respiratory tract infections (RTI) are one of the leading causes of
      under-five mortality in Bangladesh. Solid biomass fuels are the main source of
      domestic fuel used for cooking across Bangladesh, leading to smoke and pollution
      exposure in the home. This article aims to identify risk factors for RTI among
      children aged under five years in Bangladesh with a particular focus on the
      household environment, fuel use, and cooking practices. METHODS: A cross
      sectional household-health survey was carried out in 321 households in northern
      Bangladesh. The survey included care-giver interviews on cooking practices, child
      health, and household behaviors during cooking. Health status of the youngest
      child (under five years) from each household was recorded through maternal
      interviews, medical diagnosis, and assessment of biomarkers (C-reactive protein
      (CRP), hemoglobin) from finger-prick blood samples. Anthropometric status
      (weight, height) was recorded. RESULTS: Children who spent >=30 minutes/day
      within 5 feet of the stove during cooking had a significantly increased risk of
      moderate/severe RTI compared with children spending <30 minutes/day close to the
      stove (OR = 2.15, 95%CI: 1.20-3.86, P = 0.01), independent of socio-economic
      status (SES), biomass fuel type (wood, dung, plant-derived, compressed rice
      husks), child age, anthropometric status, CRP and hemoglobin. CONCLUSIONS: In
      environments with a heavy reliance on solid biomass fuels, the amount of time a
      child spends near the stove during cooking may be an important risk for RTI.
      These novel findings from Bangladesh warrant further investigation of mother
      infant behaviors during cooking in relation to child health, to ascertain whether
      the association is likely to be causal.

PMID- 25994353
TI  - A quantitative microscopic approach to predict local recurrence based on in vivo
      intraoperative imaging of sarcoma tumor margins.
AB  - The goal of resection of soft tissue sarcomas located in the extremity is to
      preserve limb function while completely excising the tumor with a margin of
      normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma
      of the extremity will have local recurrence due to microscopic residual disease
      in the tumor bed. Currently, a limited number of intraoperative pathology-based
      techniques are used to assess margin status; however, few have been widely
      adopted due to sampling error and time constraints. To aid in intraoperative
      diagnosis, we developed a quantitative optical microscopy toolbox, which includes
      acriflavine staining, fluorescence microscopy, and analytic techniques called
      sparse component analysis and circle transform to yield quantitative diagnosis of
      tumor margins. A series of variables were quantified from images of resected
      primary sarcomas and used to optimize a multivariate model. The sensitivity and
      specificity for differentiating positive from negative ex vivo resected tumor
      margins was 82 and 75%. The utility of this approach was tested by imaging the in
      vivo tumor cavities from 34 mice after resection of a sarcoma with local
      recurrence as a bench mark. When applied prospectively to images from the tumor
      cavity, the sensitivity and specificity for differentiating local recurrence was
      78 and 82%. For comparison, if pathology was used to predict local recurrence in
      this data set, it would achieve a sensitivity of 29% and a specificity of 71%.
      These results indicate a robust approach for detecting microscopic residual
      disease, which is an effective predictor of local recurrence. 

PMID- 25994354
TI  - Structural constraints on the evolution of the collagen fibril: convergence on a
      1014-residue COL domain.
AB  - Type I collagen is the fundamental component of the extracellular matrix. Its
      alpha1 gene is the direct descendant of ancestral fibrillar collagen and contains
      57 exons encoding the rod-like triple-helical COL domain. We trace the evolution
      of the COL domain from a primordial collagen 18 residues in length to its present
      1014 residues, the limit of its possible length. In order to maintain and improve
      the essential structural features of collagen during evolution, exons can be
      added or extended only in permitted, non-random increments that preserve the
      position of spatially sensitive cross-linkage sites. Such sites cannot be
      maintained unless the twist of the triple helix is close to 30 amino acids per
      turn. Inspection of the gene structure of other long structural proteins,
      fibronectin and titin, suggests that their evolution might have been subject to
      similar constraints. 

PMID- 25994355
TI  - Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in
      primary PCI: an observational comparative study.
AB  - The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be
      more potent and faster-acting antiplatelet agents than clopidogrel. This study
      aimed to investigate whether prehospital loading with prasugrel or ticagrelor
      improves early coronary reperfusion as compared to prehospital loading with
      clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting.
      Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours
      and without cardiac arrest or cardiogenic shock underwent primary percutaneous
      coronary intervention (PPCI) at our centre. The primary endpoint of this study
      was the proportion of patients who did not meet the criteria for TIMI
      (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related
      artery at initial angiography before PPCI. Prehospital loading with prasugrel (n
      = 883) or ticagrelor (n = 491) did not significantly improve coronary reperfusion
      as compared to prehospital loading with clopidogrel (n = 1,532) - a TIMI-flow 3
      at initial angiography was absent in 71.7 %, 69.0 % and 71.5 % of patients,
      respectively. Major adverse cardiac event (MACE) rates were low at 30 days (3.4 %
      to 4.0 %) and did not significantly differ between the different P2Y12 inhibitor
      regimens. In conclusion, this large observational, non-randomised study is the
      first to show that prehospital loading with the newer P2Y12 inhibitors does not
      improve early coronary reperfusion as compared to prehospital loading with
      clopidogrel in a PPCI cohort excluding cardiac arrest and cardiogenic shock. 

PMID- 25994356
TI  - Fatigue in Newly Diagnosed Inflammatory Bowel Disease.
AB  - BACKGROUND AND AIMS: The present study investigated the prevalence and severity
      of fatigue in patients with newly diagnosed and untreated ulcerative colitis (UC)
      and Crohn's disease (CD) and examined relevant disease variables that may
      influence the severity of fatigue. METHODS: Eighty-one patients with inflammatory
      bowel disease (IBD) (60 with UC and 21 with CD) were assessed for fatigue using
      two fatigue instruments: the Fatigue Severity Scale (FSS) and a fatigue visual
      analogue scale (fVAS). Cut-off for fatigue was defined as >=4 for FSS and >=50
      for fVAS. Results were compared with fatigue scores from age-and gender-matched
      healthy individuals. Disease activity was assessed by symptom scores using the
      Mayo score in UC patients and the Harvey-Bradshaw index for CD patients, as well
      as C-reactive protein (CRP) and faecal calprotectin. RESULTS: The prevalence of
      fatigue based on FSS and fVAS was 47 and 42%, respectively, in UC and 62 and 48%
      in CD. In multivariate regression models, disease activity markers were not
      associated with fatigue, while a significant relationship was found with age and
      depression for both fatigue measures. CONCLUSIONS: Close to 50% of patients with
      IBD reported fatigue at the time of diagnosis. In newly diagnosed patients with
      active disease, the severity of fatigue was not associated with measures of
      disease activity.

PMID- 25994359
TI  - Phase diagrams of nanoalloys: influence of size and morphology.
AB  - The size dependence of the phase diagram of nanoalloys with a tendency to phase
      separate is investigated. As the critical temperature may depend on both the size
      and the morphology of the nanoparticles, we consider nanowires with different
      cross-sections and also nanotubes with different circumferences. The variation of
      the critical temperature with the length of all these nanoparticles is
      systematically studied using Monte Carlo simulations based on an Ising model. A
      non-monotonic variation of the critical temperature is observed as a function of
      the length. The maximal value of the critical temperature is reached when the
      length and the circumference of the nanoparticles are similar. The phase diagrams
      obtained within two thermodynamic ensembles (the canonical ensemble and the
      pseudo grand canonical ensemble) are compared and discussed in terms of the
      behaviour of a single particle or an assembly of nanoparticles in mutual
      equilibrium with each other. 

PMID- 25994357
TI  - Results of a Nutrition and Physical Activity Peer Counseling Intervention among
      Nontraditional College Students.
AB  - Health promotion efforts targeting nontraditional college students (older, part
      time enrollment, and working) may be an optimal way to reach large populations
      that potentially face health disparities. A randomized trial was undertaken to
      examine the feasibility of a nutrition and physical activity behavioral
      intervention among nontraditional undergraduate college students at a large urban
      public university. Over 8 weeks, participants received either (1) a brief
      tailored feedback report plus three motivational interviewing-based calls from
      trained peer counselors (intervention; n = 40) or (2) the report only (control; n
      = 20). Participants mean age was 32 years (SD = 10), 58 % were female, 47 % were
      racial/ethnic minorities, and 25 % reported receiving public health insurance.
      Most (78 %) intervention group participants completed at least two of three peer
      counseling calls. At follow-up, those in the intervention vs. control group self
      reported beneficial, but non-statistically significant changes in fruits and
      vegetables (+0.7 servings/day), sugary drinks (-6.2 oz/day), and fast food visits
      (-0.2 visits/week). For physical activity, there was a non-statistically
      significant decrease in moderate-vigorous physical activity (107.2 min/week) in
      the intervention vs. CONTROL GROUP: Overall satisfaction with the program was
      high, although there were recommendations made for improving the structure and
      number of calls. Findings indicate that the intervention was feasible with
      promising effects on nutrition behaviors and the need to better target physical
      activity behaviors. Future work entails implementation in a larger sample with
      objectively measured behaviors.

PMID- 25994358
TI  - Information Needs of Cancer Patients and Perception of Impact of the Disease, of
      Self-Efficacy, and Locus of Control.
AB  - The aim of our study was to investigate the relationship between information
      needs and cancer patients' perceptions of the impact of the disease, self
      efficacy, and locus of control. Using a standardized questionnaire, we obtained
      data from patients who attended a series of lectures. The questionnaire included
      questions on their information needs, sources of information, satisfaction with
      information, and short questionnaires on self-efficacy, perception of the
      disease, and locus of control of reinforcement. Data was obtained from 185
      patients. Our results showed that the sources of information that were most often
      used were physicians (84 %), print media (68 %), and the Internet (59 %); online
      fora (7.5 %), non-medical practitioners (9.7 %), and telephone-based counseling
      (8.6 %) were only used by a minority. Patients with a high perception of their
      own control over the disease more often used any source of information available
      to them and were more often interested in acquiring additional information.
      Higher self-efficacy was significantly associated with the need for information
      on all topics. Patients with a higher external locus of control significantly
      more often used sources of information and had significantly more need for
      additional information. By contrast, there were no associations with an internal
      locus of control. Neither external nor internal locus of control showed any
      associations with satisfaction with information. Information needs seem to be
      higher in patients with a high external locus of control and low self-efficacy.
      Physicians, other professionals, and institutions that provide information may
      take these relationships into consideration for tailoring their services to
      patients.

PMID- 25994361
TI  - Rapid learning of minimally different words in five- to six-year-old children:
      effects of acoustic salience and hearing impairment.
AB  - This study investigates the role of acoustic salience and hearing impairment in
      learning phonologically minimal pairs. Picture-matching and object-matching tasks
      were used to investigate the learning of consonant and vowel minimal pairs in
      five- to six-year-old deaf children with a cochlear implant (CI), and children of
      the same age with normal hearing (NH). In both tasks, the CI children showed
      clear difficulties with learning minimal pairs. The NH children also showed some
      difficulties, however, particularly in the picture-matching task. Vowel minimal
      pairs were learned more successfully than consonant minimal pairs, particularly
      in the object-matching task. These results suggest that the ability to encode
      phonetic detail in novel words is not fully developed at age six and is affected
      by task demands and acoustic salience. CI children experience persistent
      difficulties with accurately mapping sound contrasts to novel meanings, but seem
      to benefit from the relative acoustic salience of vowel sounds.

PMID- 25994360
TI  - Impact of policies regulating foreign physician migration to Switzerland: a
      modelling case study in anaesthesia.
AB  - BACKGROUND: Several countries have developed policies that restrict or limit
      duration of stay, clinical privileges or the number of residency permits
      allocated to migrating physicians. Switzerland is currently preparing a new law
      limiting overall foreign immigration. The impact of such restrictive policies is
      currently unknown. In a case study of anaesthesia care in Switzerland we
      modelled, trends in the size of physicians' workforce until 2024, following the
      implementation of a strict quota policy for foreign medical trainees. METHODS: We
      developed a computer-based Markov model with Monte-Carlo simulations to project,
      in the context of a strict quota policy for foreign trainees, supply and demand
      for anaesthesia positions until 2024. We used data from a cross-sectional study
      performed in the French- and Italian-speaking cantons of Switzerland and the
      Health dataset from the OECD. RESULTS: With 8 to 12 (95% CI 4-20) anaesthetists
      retiring per year, the implementation of strict quotas of foreign graduates would
      result in a 38% decrease in the number of anaesthetists in intermediary (senior
      registrars) positions by 2024. This decrease would be particularly important in
      district hospitals where nearly half (49%) of the non-Swiss anaesthetists are
      practising. Swiss graduates are unlikely to balance the shortage. Despite efforts
      by Swiss universities to increase the number of medical graduates, their number
      has dropped from 10.5 to 9.7/100 000 inhabitants between 2000 and 2012, due to
      the growth of the population. CONCLUSIONS: This case study in Latin Switzerland
      shows that a restrictive policy limiting foreign immigration of trainees would
      result in a major deficit in the number of anaesthetists available to meet
      population needs. These aspects should be carefully considered when countries
      develop restrictions and limitations of foreign immigration.

PMID- 25994362
TI  - An iodine catalyzed metal free domino process for the stereoselective synthesis
      of oxygen bridged bicyclic ethers.
AB  - A domino reaction has been developed for the synthesis of oxygen bridged bicyclic
      ethers through the coupling of 4-(2-hydroxyethyl)cyclohex-3-enols with aldehydes
      in the presence of 10 mol% of molecular iodine in dichloromethane at 25  degrees
      C. This method is highly diastereoselective affording the corresponding bicyclic
      ethers, i.e. octahydro-4a,7-epoxyisochromenes in good yields with high
      selectivity. It is the first report on the synthesis of oxygen bridged bicyclic
      ethers using a domino Prins strategy. 

PMID- 25994363
TI  - Investigating intracerebral haemorrhage.

PMID- 25994364
TI  - Mortality of People with Intellectual and Developmental Disabilities from Select
      US State Disability Service Systems and Medical Claims Data.
AB  - BACKGROUND: Monitoring population trends including mortality within subgroups
      such as people with intellectual and developmental disabilities and between
      countries provides crucial information about the population's health and insights
      into underlying health concerns and the need for and effectiveness of public
      health efforts. METHODS: Data from both US state intellectual and developmental
      disabilities service system administrative data sets and de-identified state
      Medicaid claims were used to calculate average age at death and crude mortality
      rates. RESULTS: Average age at death for people in state intellectual and
      developmental disabilities systems was 50.4-58.7 years and 61.2-63.0 years in
      Medicaid data, with a crude adult mortality rate of 15.2 per thousand.
      CONCLUSIONS: Age at death remains lower and mortality rates higher for people
      with intellectual and developmental disabilities. Improved case finding (e.g.
      medical claims) could provide more complete mortality patterns for the population
      with intellectual and developmental disabilities to inform the range of access
      and receipt of supportive and health-related interventions and preventive care.

PMID- 25994365
TI  - The effect of gold(I) coordination on the dual fluorescence of 4
      (dimethylamino)pyridine.
AB  - The reactions of 4(dimethylamino)pyridine (DMAP) with the gold(I) precursors
      [AuR(tht)] (R = C6F5, C6Cl2F3 or C6Cl5; tht = tetrahydrothiophene) lead to
      complexes [AuR(DMAP)] (R = C6F5 (1), C6Cl2F3 (2) or C6Cl5 (3)). X-ray diffraction
      studies of the complexes reveal the presence of discrete molecules in which
      aurophilic contacts are absent, with pi-stacking (1) or hydrogen bond (2)
      interactions being responsible for the supramolecular arrangements found in the
      solid state. All complexes display fluorescence in solution in solvents of
      different polarities such as toluene, chloroform or acetonitrile. In all cases
      the emission energy is similar to the low-energy Twisted Intramolecular Charge
      Transfer (TICT) emission of free DMAP. TDDFT calculations confirm that the
      fluorescence of complexes 1-3 arises from the ICT excited state of bonded DMAP in
      which a 90 degrees  distortion of the pyridine ring and -NMe2 planes is observed.
      Model calculations based on experimental parameters show a higher degree of
      polarization of DMAP upon coordination to Au(I) organometallic fragments.

PMID- 25994366
TI  - Alginate dressings for treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and
      pressure injuries, are localised areas of injury to the skin or the underlying
      tissue, or both. Dressings are widely used to treat pressure ulcers and there are
      many options to choose from including alginate dressings. A clear and current
      overview of current evidence is required to facilitate decision-making regarding
      dressing use for the treatment of pressure ulcers. This review is part of a suite
      of Cochrane reviews investigating the use of dressings in the treatment of
      pressure ulcers. Each review will focus on a particular dressing type.
      OBJECTIVES: To assess the effects of alginate dressings for treating pressure
      ulcers in any care setting. SEARCH METHODS: For this review, in April 2015 we
      searched the following 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; and EBSCO CINAHL. There were no restrictions based on language or
      date of publication. SELECTION CRITERIA: Published or unpublished randomised
      controlled trials (RCTs) comparing the effects of alginate with alternative wound
      dressings or no dressing in the treatment of pressure ulcers (stage II or above).
      DATA COLLECTION AND ANALYSIS: Two review authors independently performed study
      selection, risk of bias assessment and data extraction. MAIN RESULTS: We included
      six studies (336 participants) in this review; all studies had two arms. The
      included studies compared alginate dressings with six other interventions that
      included: hydrocolloid dressings, silver containing alginate dressings, and
      radiant heat therapy. Each of the six comparisons included just one study and
      these had limited participant numbers and short follow-up times. All the evidence
      was of low or very low quality. Where data were available there was no evidence
      of a difference between alginate dressings and alternative treatments in terms of
      complete wound healing or adverse events. AUTHORS' CONCLUSIONS: The relative
      effects of alginate dressings compared with alternative treatments are unclear.
      The existing trials are small, of short duration and at risk of bias. Decision
      makers may wish to consider aspects such as cost of dressings and the wound
      management properties offered by each dressing type, for example, exudate
      management.

PMID- 25994367
TI  - MR-PET co-registration in upper abdominal imaging: quantitative comparison of two
      different T1-weighted gradient echo sequences: initial observations.
AB  - PURPOSE: The purpose of this study is to quantitatively compare the accuracy of
      spatial registration of Cartesian breath-hold 3D-GRE and non-respiratory
      triggered free-breathing radial 3D-GRE images with PET data acquisition on whole
      body hybrid MR-PET system. MATERIALS AND METHODS: Eight patients (six men and two
      women; mean age, 56.6 +/- 5.5 years) with nine ablated hepatocellular carcinomas
      constituted our study population. Spatial coordinates (x, y, z) of the estimated
      isocenters of the ablated areas were independently determined by two
      radiologists. Both T1-weighted sequences were performed in the axial plane.
      Distance between the isocenter of the lesion on PET images and on both T1
      weighted images was measured, and misregistration was calculated. Statistical
      analysis was performed using Student t test. RESULTS: Misalignment values of the
      hepatic ablation zones between PET and MR images were calculated at 4.94 +/- 1.35
      mm (reader 1) and 4.89 +/- 2.21 mm (reader 2) for Cartesian 3D-GRE sequence, and
      2.48 +/- 0.65 mm (reader 1) and 2.72 +/- 0.44 mm (reader 2) for the radial 3D-GRE
      sequence, with p values of 0.0011 and 0.0133, respectively. CONCLUSION: Radial 3D
      GRE offers improved registration accuracy with PET, supporting the use of this T1
      weighted sequence in upper abdominal MR-PET studies.

PMID- 25994368
TI  - Bismuth nanoparticles integration into heavy metal electrochemical stripping
      sensor.
AB  - Between their many applications bismuth nanoparticles (BiNPs) are showing
      interest as pre-concentrators in heavy metals detection while being applied as
      working electrode modifiers used in electrochemical stripping analysis. From the
      different reported methods to synthesize BiNPs we are focused on the typical
      polyol method, largely used in these types of metallic and semi-metallic
      nanoparticles. This study presents the strategy for an easy control of the shape
      and size of BiNPs including nanocubes, nanosferes and triangular nanostructures.
      To improve the BiNP size and shape, different reducing agents (ethylene glycol or
      sodium hypophosphite) and stabilizers (polyvinyl pyrrolidone, PVP, in different
      amounts) have been studied. The efficiency of BiNPs for heavy metals analysis in
      terms of detection sensitivity while being used as modifiers of screen-printed
      carbon electrodes including the applicability of the developed device in real sea
      water samples is shown. A parallel study between the obtained nanoparticles and
      their performance in heavy metal sensing has been described in this
      communication. 

PMID- 25994369
TI  - Challenges with AST/ALT ratio in acetaminophen poisoning--the authors reply.

PMID- 25994370
TI  - The use of interventional ultrasound in physiatry: single-center one-year
      analysis.

PMID- 25994371
TI  - Classification of functioning and assessment of fracture risk of a large Italian
      osteoporotic population. The Physiatric Approach To Osteoporosis project.
AB  - BACKGROUND: Osteoporosis is a skeletal disorder characterized by compromised bone
      strength predisposing to an increased risk of fracture. Osteoporotic fractures
      cause significant morbidity, disability, and decrease in quality of life. AIM:
      The aims of the Physiatric Approach To Osteoporosis (PATO) project were to
      classify osteoporotic patients with or without fragility fractures, using the
      Brief ICF (International Classification of Functioning, Disability and Health)
      Core Set for Osteoporosis and to calculate the fracture risk with the WHO FRAX(r)
      (World Health Organization Fracture Risk Assessment Tool) algorithm. DESIGN:
      Cross-sectional survey. SETTING: Seventy-nine Italian Rehabilitation Services
      distributed throughout Italy. POPULATION: Osteoporotic patients. METHODS: Each
      physiatrist involved in the survey was asked systematically to record demographic
      data, presence of fragility fractures, anamnestic risk factors included in the
      FRAX(r) Assessment Tool, ICF categories as they are listed in the Brief ICF Core
      Set for Osteoporosis, and treatment data of 100 osteoporotic patients (50 with at
      least a clinical fragility fracture and 50 without). RESULTS: In accordance with
      the FRAX(r) algorithm, the 35.22% of the interviewed osteoporotic patients had a
      FRAX(r) MAJ>=20.00 and the 70.32% had a FRAX(r) HIP>=3.00. The most commonly
      impaired ICF categories were the sensation of pain for the body functions, the
      structure of the trunk for body structures, lifting and carrying objects for the
      domain of activities and participation, and products or substances for personal
      consumption for the environmental factors. CONCLUSION: The FRAX(r) Assessment
      tool has been recognized as useful to identify people at high risk of fracture
      and the Brief ICF Core Set seems to be an important framework to be followed when
      dealing with osteoporotic patients in an outpatient setting or for clinical
      studies. CLINICAL REHABILITATION IMPACT: Osteoporosis is well recognized as a
      disabling disease, posing a significant challenge for the society, therefore
      physiatrists should always be involved, from prevention to treatment.

PMID- 25994372
TI  - Long-term outcomes of powered endoscopic dacryocystorhinostomy in acute
      dacryocystitis.
AB  - OBJECTIVES/HYPOTHESIS: Endoscopic dacryocystorhinostomy (DCR) is rapidly gaining
      recognition as a primary modality of management in acute dacryocystitis and
      lacrimal abscess. The purpose of the present study is to report long-term
      outcomes of powered endoscopic DCR in cases of acute dacryocystitis. STUDY
      DESIGN: Prospective interventional case series. METHODS: Twenty-one powered
      endoscopic DCRs were performed in 21 patients presenting with acute
      dacryocystitis. All cases were operated by a single surgeon (m.j.a.) using
      earlier published techniques. All lacrimal systems were intubated for 6 weeks. A
      minimum follow-up of 1 year after stent removal was considered for final
      analysis. Main outcome measures were the anatomical and functional success of the
      surgical procedure. RESULTS: The mean age of patients at presentation was 31.8
      years. A total of 14.3% (3/21) were pediatric patients with known history of
      persistent congenital nasolacrimal duct obstruction (CNLDO), and 9.5% (2/21) had
      a history of external DCR in the past. All patients received postoperative
      antibiotics. Additional procedures included distal canalicular trephination,
      septoplasty, and middle turbinoplasty in one patient each. All cases showed
      resolution of pain and swelling at 1 week follow-up. At the mean follow-up of
      15.4 months, anatomical success was achieved in 85.7% of the patients (18/21),
      and functional success was achieved in 80.9% (17/21). CONCLUSION: Powered
      endoscopic DCR is a useful modality in the management acute dacryocystitis, with
      good outcomes that are maintained over a long duration of time. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 126:551-553, 2016.

PMID- 25994373
TI  - Gossypetin ameliorates ionizing radiation-induced oxidative stress in mice liver-
      a molecular approach.
AB  - Radioprotective action of gossypetin (GTIN) against gamma (gamma)-radiation
      induced oxidative stress in liver was explored in the present article. Our main
      aim was to evaluate the protective efficacy of GTIN against radiation-induced
      alteration of liver in murine system. To evaluate the effect of GTIN, it was
      orally administered to mice at a dose of 30 mg/kg body weight for three
      consecutive days prior to gamma-radiation at a dose of 5 Gy. Radioprotective
      efficacy of GTIN were evaluated at physiological, cellular, and molecular level
      using biochemical analysis, comet assay, flow cytometry, histopathology,
      immunofluorescence, and immunoblotting techniques. Ionizing radiation was
      responsible for augmentation of hepatic oxidative stress in terms of lipid
      peroxidation and depletion of endogenous antioxidant enzymes. Immunoblotting and
      immunofluorescence studies showed that irradiation enhanced the nuclear
      translocation of nuclear factor kappa B (NF-kappaB) level, which leads to hepatic
      inflammation. To investigate further, we found that radiation induced the
      activation of stress-activated protein kinase/c-Jun NH2-terminal kinase
      (SAPK/JNK)-mediated apoptotic pathway and deactivation of the NF-E2-related
      factor 2 (Nrf2)-mediated redox signaling pathway, whereas GTIN pretreatment
      ameliorated these radiation-mediated effects. This is the novel report where GTIN
      rationally validated the molecular mechanism in terms of the modulation of
      cellular signaling system' instead of ' This is the novel report where GTIN is
      rationally validated in molecular terms to establish it as promising
      radioprotective agents. This might be fruitful especially for nuclear workers and
      defense personnel assuming the possibility of radiation exposure. 

PMID- 25994374
TI  - Characterization of neural stem cells and their progeny in the sensory
      circumventricular organs of adult mouse.
AB  - Although evidence has accumulated that neurogenesis and gliogenesis occur in the
      subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains,
      recent studies indicate the presence of neural stem cells (NSCs) in adult brains,
      particularly the circumventricular regions. In the present study, we aimed to
      determine characterization of NSCs and their progenitor cells in the sensory
      circumventricular organs (CVOs), including organum vasculosum of the lamina
      terminalis, subfornical organ, and area postrema of adult mouse. There were two
      types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte
      like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and
      neural progenitor cells (NPCs) actively divided. Molecular marker protein
      expression of NSCs and their progenitor cells were similar to those reported in
      the SVZ and SGZ, except that astrocyte-like NSCs expressed S100beta. These
      circumventricular NSCs possessed the capacity to give rise to oligodendrocytes
      and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent
      brain regions. The inhibition of vascular endothelial growth factor (VEGF)
      signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171
      largely suppressed basal proliferation of OPCs. A single systemic administration
      of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable
      proliferation of microglia. The present study indicates that sensory
      circumventricular NSCs provide new neurons and glial cells in the sensory CVOs
      and adjacent brain regions. 

PMID- 25994376
TI  - Abstracts of the 102nd annual congress of the swiss society of surgery, berne,
      Switzerland, 20-22 may 2015.

PMID- 25994375
TI  - Analysis of large mutations in BARD1 in patients with breast and/or ovarian
      cancer: the Polish population as an example.
AB  - Only approximately 50% of all familial breast cancers can be explained by known
      genetic factors, including mutations in BRCA1 and BRCA2. One of the most
      extensively studied candidates for breast and/or ovarian cancer susceptibility is
      BARD1. Although it was suggested that large mutations may contribute
      substantially to the deleterious variants of BARD1, no systematic study of the
      large mutations in BARD1 has been performed. To further elucidate the role of
      large mutations in BARD1, we designed a multiplex ligation-dependent probe
      amplification (MLPA) assay and performed an analysis of 504 women with a familial
      breast and/or ovarian cancer and 313 patients with ovarian cancer. The
      investigation did not reveal any large mutations in the BARD1 gene. Although the
      analysis was not focused on identification of small mutations, we detected seven
      deleterious or potentially deleterious point mutations, which contribute
      substantially to the total number of BARD1 mutations detected so far. In
      conclusion, although we cannot exclude the presence of large mutations in BARD1,
      our study indicates that such mutations do not contribute substantially to the
      risk of breast and/or ovarian cancer. However, it has to be noted that our
      results may be specific to the Polish population. 

PMID- 25994377
TI  - Field-Induced Crystalline-to-Amorphous Phase Transformation on the Si Nano-Apex
      and the Achieving of Highly Reliable Si Nano-Cathodes.
AB  - Nano-scale vacuum channel transistors possess merits of higher cutoff frequency
      and greater gain power as compared with the conventional solid-state transistors.
      The improvement in cathode reliability is one of the major challenges to obtain
      high performance vacuum channel transistors. We report the experimental findings
      and the physical insight into the field induced crystalline-to-amorphous phase
      transformation on the surface of the Si nano-cathode. The crystalline Si tip apex
      deformed to amorphous structure at a low macroscopic field (0.6~1.65 V/nm) with
      an ultra-low emission current (1~10 pA). First-principle calculation suggests
      that the strong electrostatic force exerting on the electrons in the surface
      lattices would take the account for the field-induced atomic migration that
      result in an amorphization. The arsenic-dopant in the Si surface lattice would
      increase the inner stress as well as the electron density, leading to a lower
      amorphization field. Highly reliable Si nano-cathodes were obtained by employing
      diamond like carbon coating to enhance the electron emission and thus decrease
      the surface charge accumulation. The findings are crucial for developing highly
      reliable Si-based nano-scale vacuum channel transistors and have the significance
      for future Si nano-electronic devices with narrow separation. 

PMID- 25994378
TI  - Adsorption of cinnabarinic acid from culture fluid with magnetic microbeads.
AB  - In this study, antimicrobial pigment cinnabarinic acid (CA) was produced from
      Pycnoporus cinnabarinus in laboratory-scale batch cultures. Magnetic
      poly(ethylene glycol dimethacrylate-N-methacryloyl-l-tryptophan methyl ester) [m
      poly(EGDMA-MATrp)] beads (average diameter = 53-103 um) were synthesized by
      copolymerizing of N-methacryloyl-l-tryptophan methyl ester (MATrp) with ethylene
      glycol dimethacrylate (EGDMA) in the presence of magnetite (Fe3O4) and used for
      the adsorption of CA. The m-poly(EGDMA-MATrp) beads were characterized by N2
      adsorption/desorption isotherms (Brunauer Emmet Teller), X-ray photoelecron
      spectroscopy, scanning electron microscopy, infrared spectroscopy, thermal
      gravimetric analysis, electron spin resonance and swelling studies. The
      efficiency of m-poly(EGDMA-MATrp) beads for separation of CA from culture fluid
      was evaluated. The effects of pH, initial concentration, contact time and
      temperature on adsorption were analyzed. The maximum CA adsorption capacity of
      the m-poly(EGDMA-MATrp) beads was 272.9 mg g(-1) at pH 7.0, 25  degrees C. All
      the isotherm data can be fitted with the Langmuir, Freundlich and Dubinin
      Radushkevich isotherm models. The adsorption process obeyed pseudo-second-order
      kinetic model. Thermodynamic parameters DeltaH = 5.056 kJ mol(-1), DeltaS = 52.44
      J K(-1)  mol(-1) and DeltaG = -9.424 kJ mol-(1) to -11.27 kJ mol-(1) with the
      rise in temperature from 4 to 40  degrees C indicated that the adsorption process
      was endothermic and spontaneous.

PMID- 25994379
TI  - Reconfigurable microfluidic dilution for high-throughput quantitative assays.
AB  - This paper reports a reconfigurable microfluidic dilution device for high
      throughput quantitative assays, which can easily produce discrete
      logarithmic/binary concentration profiles ranging from 1 to 100-fold dilution in
      parallel from a fixed sample volume (e.g., 10 MUL) without any assistance of
      continuous fluidic pump or robotic automation. The integrated dilution generation
      chip consists of switchable distribution and collection channels, metering
      reservoirs, reaction chambers, and pressure-activatable Laplace valves. Following
      the sequential loading of a sample, a diluent, and a detection reagent into their
      individual metering chambers, the top microfluidic layer can be reconfigured to
      collect the metered chemicals into the reaction chambers in parallel, where
      detection will be conducted. To facilitate mixing and reaction in the
      microchambers, two acoustic microstreaming actuation mechanisms have been
      investigated for easy integrability and accessibility. Furthermore, the
      microfluidic dilution generator has been characterized by both colorimetric and
      fluorescent means. A further demonstration of the generic usage of the
      quantitative dilution chip has utilized the commonly available bicinchoninic acid
      (BCA) assay to analyse the protein concentrations of human tissue extracts. In
      brief, the microfluidic dilution generator offers a high-throughput high
      efficiency quantitative analytical alternative to conventional quantitative assay
      platforms, by simple manipulation of a minute amount of chemicals in a compact
      microfluidic device with minimal equipment requirement, which can serve as a
      facile tool for biochemical and biological analyses in regular laboratories,
      point-of-care settings and low-resource environments. 

PMID- 25994380
TI  - Focus on epistaxis.

PMID- 25994381
TI  - Enhanced recovery programmes in head and neck surgery: systematic review.
AB  - OBJECTIVE: To review the literature on enhanced recovery programmes in head and
      neck surgery. METHOD: A systematic review was performed in May 2013. RESULTS:
      Thirteen articles discussing enhanced recovery after laryngectomy, neck
      dissection, major ablative surgery and microvascular reconstruction were
      identified. Articles on general pre-operative preparation and post-operative care
      were also reviewed. CONCLUSION: Considerable evidence is available supporting
      enhanced recovery in head and neck surgery that could be of benefit to patients
      and which surgeons should be aware of.

PMID- 25994382
TI  - Surgical management of medullary thyroid cancer: which guidelines should we
      follow?
AB  - BACKGROUND: Surgery is currently the only curative treatment for medullary
      thyroid cancer. Unfortunately, the surgical strategy that will offer patients at
      each disease stage the best chance of a biochemical cure remains unclear. The
      American Thyroid Association and British Thyroid Association guidelines offer
      different strategies. METHODS: A retrospective analysis of the surgical
      management of 47 patients with medullary thyroid cancer diagnosed between 1994
      and 2013 was performed. Surgical management was compared with current American
      Thyroid Association and British Thyroid Association guidelines. Outcome was
      defined as the first post-operative calcitonin measurement. RESULTS: All patients
      with stage I-III disease achieved a post-operative biochemical cure regardless of
      the guidelines followed. The overall biochemical cure rate for patients with
      stage IVa disease was significantly reduced to 10 per cent (p < 0.01), but the
      biochemical cure rate for stage IVa disease patients who underwent bilateral
      lateral lymph node dissection was 33.3 per cent. CONCLUSION: The conservative,
      surveillance-driven approach recommended by the American Thyroid Association is
      appropriate for stage I-III disease. However, the more aggressive approach
      advocated by the British Thyroid Association might provide stage IVa disease
      patients a greater chance of achieving a biochemical cure.

PMID- 25994383
TI  - On the minimum requirements for otolaryngology clinics in National Health Service
      hospitals.
AB  - OBJECTIVE: This paper, a report by the Clinical Governance and Audit Committee of
      the Scottish Otolaryngological Society, presents a consensus view of the minimal
      requirements for ENT clinics in National Health Service hospitals. RESULTS AND
      CONCLUSION: The provision of adequate equipment and staff has gained increasing
      importance as the vast majority of ENT procedures can be safely performed in the
      out-patient or office setting.

PMID- 25994384
TI  - Open surgical management of auricular haematoma: incision, evacuation and
      mattress sutures.
AB  - OBJECTIVE: A large variety of techniques have been used for auricular haematoma
      management. The open surgical management of auricular haematoma involves
      incision, evacuation and the obliteration of dead space using biodegradable
      mattress sutures. Our goal was to describe open surgical management for primary,
      recurrent and spontaneous auricular haematoma. METHODS: Auricular haematoma
      patients who underwent open surgical management were prospectively audited (2010
      2013). Information was collected on demographics, clinical presentation,
      aetiology, examination findings, previous interventions, details of open surgical
      management and post-operative follow up. RESULTS: In all, 12 male and 3 female
      patients with a mean age of 33 years (range 16-86 years) were evaluated. Contact
      sport injury was the most common aetiology. Ten patients had undergone previous
      unsuccessful interventions to treat auricular haematoma before open surgical
      management was performed. All patients were managed successfully without
      significant recurrence. One patient had a minor local reaccumulation which
      required reinsertion of a mattress suture. One elderly patient developed
      localised cellulitis which responded well to antibiotics. CONCLUSION: Open
      surgical management of auricular haematoma has been successful. The technique is
      simple and reliable, and can be accomplished in a clinical setting under local
      anaesthesia.

PMID- 25994385
TI  - Auditory neuropathy spectrum disorder with Brown-Vialetto-Van Laere syndrome:
      challenges in hearing rehabilitation.
AB  - BACKGROUND: Brown-Vialetto-Van Laere syndrome is a rare neurological disorder
      characterised by pontobulbar palsy and sensorineural hearing loss. Hearing
      rehabilitation continues to be a challenge because the exact lesion site is
      unknown. CASE REPORT: We examined the clinical and audiological profiles of a
      case series comprising four siblings with Brown-Vialetto-Van Laere syndrome who
      had decreased hearing and poor speech discrimination. Audiological investigations
      revealed normal otoacoustic emissions with absent auditory brainstem responses
      and middle-ear reflexes in sensorineural hearing loss, suggestive of auditory
      neuropathy spectrum disorder. CONCLUSION: The sensorineural hearing loss in Brown
      Vialetto-Van Laere syndrome patients is a retrocochlear pathology resembling
      auditory neuropathy spectrum disorder, with the lesion being most probably of
      post-synaptic origin. Early cochlear implantation along with high-dose riboflavin
      represents a possible rehabilitation therapy. However, further research is needed
      to confirm this. This report emphasises the need for a thorough neurological
      evaluation of auditory neuropathy spectrum disorder patients.

PMID- 25994387
TI  - The structure and elastic properties of phosphorene edges.
AB  - We investigated the edge atomic structures and elastic properties of defect-free
      phosphorene nanoribbons (PNRs). Density functional tight binding simulations were
      used to optimize two main edge configurations: armchair (AC) and zigzag (ZZ). It
      was found that the energy relaxation of PNRs leads to the noticeable changes in
      edge atomic configurations. The effective width of the edge region, which
      includes all the atoms involved in the edge relaxation, was found to contain
      approximately three atomic rows near the edge for both AC and ZZ PNRs. We further
      extracted the edge stress and modulus for the ZZ and AC edges. Both the AC and ZZ
      edge stresses of PNRs are positive, indicating tensile stress at the edges. In
      addition, both the AC and ZZ edge moduli are positive. However, the edge elastic
      modulus and edge stress of ZZ PNRs are about three times larger than those of AC
      PNRs. Furthermore, we showed that the tensile edge stresses along ZZ and AC edges
      are able to cause distortion in freestanding phosphorene nanoribbons. Our results
      highlight the importance of accounting for edge stresses in the design and
      fabrication of PNRs. 

PMID- 25994386
TI  - Complex network models reveal correlations among network metrics, exercise
      intensity and role of body changes in the fatigue process.
AB  - The aims of the present study were analyze the fatigue process at distinct
      intensity efforts and to investigate its occurrence as interactions at distinct
      body changes during exercise, using complex network models. For this,
      participants were submitted to four different running intensities until
      exhaustion, accomplished in a non-motorized treadmill using a tethered system.
      The intensities were selected according to critical power model. Mechanical
      (force, peak power, mean power, velocity and work) and physiological related
      parameters (heart rate, blood lactate, time until peak blood lactate
      concentration (lactate time), lean mass, anaerobic and aerobic capacities) and
      IPAQ score were obtained during exercises and it was used to construction of four
      complex network models. Such models have both, theoretical and mathematical
      value, and enables us to perceive new insights that go beyond conventional
      analysis. From these, we ranked the influences of each node at the fatigue
      process. Our results shows that nodes, links and network metrics are sensibility
      according to increase of efforts intensities, been the velocity a key factor to
      exercise maintenance at models/intensities 1 and 2 (higher time efforts) and
      force and power at models 3 and 4, highlighting mechanical variables in the
      exhaustion occurrence and even training prescription applications. 

PMID- 25994388
TI  - Twofold polyketide branching by a stereoselective enzymatic Michael addition.
AB  - The versatility of the branching module of the rhizoxin polyketide synthase was
      tested in an in vitro enzyme assay with a polyketide mimic and branched
      (di)methylmalonyl-CoA extender units. Comparison of the products with synthetic
      reference compounds revealed that the module is able to stereoselectively
      introduce two branches in one step by a Michael addition-lactonisation sequence,
      thus expanding the scope of previously studied PKS systems. 

PMID- 25994389
TI  - Lipid subclasses profiles and oxidative stress in aggressive periodontitis before
      and after treatment.
AB  - BACKGROUND AND OBJECTIVE: Associations between dyslipidaemia, oxidative stress
      and periodontitis have emerged in recent years. However, there is a lack of
      studies investigating these associations in aggressive periodontitis (AgP) cases.
      The aim of this study was to investigate the lipid and oxidative stress profiles
      in patients with AgP, and to relate them to clinical variables and interleukin
      (IL)-6 genetic variants. MATERIAL AND METHODS: Twelve non-smoking Caucasian
      patients with AgP selected based on their IL6 haplotypes underwent periodontal
      non-surgical and surgical treatment. Peripheral blood samples taken at baseline
      and at six different time-points after treatment were processed to determine IL-6
      circulating levels, lipid profiles (cholesterol, triglycerides, high-density
      lipoprotein [HDL] and low-density lipoprotein [LDL] subclasses) and oxidative
      stress markers (glutathione and total lipid hydroperoxide levels). RESULTS: HDLs
      were the most prevalent lipoproteins, followed by intermediate-density
      lipoprotein, very-low-density lipoprotein and LDL. The LDL subclasses consisted
      mainly of the less atherogenic large LDL. The lipid profile did not consistently
      change after treatment up to 3 mo after surgery. Periodontal disease severity was
      associated with LDL levels and size. The IL6 haplotypes were associated with
      total cholesterol, triglycerides, HDL and LDL subclasses after adjusting for
      confounders. IL-6 circulating levels were associated with both very-low-density
      lipoprotein and lipid hydroperoxide levels. CONCLUSION: Based on these data, we
      conclude that both periodontal disease severity and IL6 haplotypes may influence
      lipid profiles in AgP.

PMID- 25994391
TI  - Use of Synchrotron Radiation-Analytical Techniques To Reveal Chemical Origin of
      Silver-Nanoparticle Cytotoxicity.
AB  - To predict potential medical value or toxicity of nanoparticles (NPs), it is
      necessary to understand the chemical transformation during intracellular
      processes of NPs. However, it is a grand challenge to capture a high-resolution
      image of metallic NPs in a single cell and the chemical information on
      intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X
      ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES)
      spectroscopy, we successfully capture the 3D distribution of silver NPs (AgNPs)
      inside a single human monocyte (THP-1), associated with the chemical
      transformation of silver. The results reveal that the cytotoxicity of AgNPs is
      largely due to the chemical transformation of particulate silver from elemental
      silver (Ag(0))n, to Ag(+) ions and Ag-O-, then Ag-S- species. These results
      provide direct evidence in the long-lasting debate on whether the nanoscale or
      the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the
      present approach provides an integrated strategy capable of exploring the
      chemical origins of cytotoxicity in metallic nanoparticles. 

PMID- 25994392
TI  - Determination of 4(5)-methylimidazole in carbonated beverages by isotope-dilution
      liquid chromatography-tandem mass spectrometry.
AB  - The purpose of this study was to develop a method to quantify 4(5)
      methylimidazole (4-MEI), a suspected carcinogen, in carbonated beverages by
      simple sample dilution and isotope-dilution reverse-phase LC-MS/MS. Isotope
      dilution using hexa-deuterated methylimidazole (d6-4-MEI) was used to quantify
      native 4-MEI and to assess matrix effects quantitatively. The accuracy of the
      method was assessed by intentionally fortifying a negative control sample at
      three doses: low, medium and high (replicates of n = 5 each) with a known amount
      of 4-MEI. The respective absolute error in each case was 18.7 +/- 0.7%, 14.6 +/-
      2.8% and 21.1 +/- 9.7%. Within-day (intra-) and day-to-day (inter-)
      repeatability, determined as the relative standard deviation by fortifying a
      negative control sample (n = 5), were 9.5% and 15.4%, respectively. Average ion
      suppression of d6-4-MEI in beer was 63.9 +/- 3.2%, while no suppression or
      enhancement was seen in non-alcoholic samples. The instrument and method limit of
      detection were calculated as 0.6 and 5.8 ng ml(-1), respectively. 4(5)
      Methylimidazole was quantified in a variety of store-bought consumer beverages
      and it was found that in many of the samples tested consuming a single can of
      beer would result in intake levels of 4-MEI that exceed the no significant risk
      guideline of 29 ug day(-1). Conversely, 4-MEI in the samples was orders of
      magnitude smaller than the European Food Safety Authority acceptable daily intake
      threshold value of 100 mg kg(-1) bw day(-1).

PMID- 25994390
TI  - User-initialized active contour segmentation and golden-angle real-time
      cardiovascular magnetic resonance enable accurate assessment of LV function in
      patients with sinus rhythm and arrhythmias.
AB  - BACKGROUND: Data obtained during arrhythmia is retained in real-time
      cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent
      evidence to show that rt-CMR can accurately assess beat-to-beat variation in left
      ventricular (LV) function or during an arrhythmia. METHODS: Multi-slice, short
      axis cine and real-time golden-angle radial CMR data was collected in 22 clinical
      patients (18 in sinus rhythm and 4 patients with arrhythmia). A user-initialized
      active contour segmentation (ACS) software was validated via comparison to manual
      segmentation on clinically accepted software. For each image in the 2D
      acquisitions, slice volume was calculated and global LV volumes were estimated
      via summation across the LV using multiple slices. Real-time imaging data was
      reconstructed using different image exposure times and frame rates to evaluate
      the effect of temporal resolution on measured function in each slice via ACS.
      Finally, global volumetric function of ectopic and non-ectopic beats was measured
      using ACS in patients with arrhythmias. RESULTS: ACS provides global LV volume
      measurements that are not significantly different from manual quantification of
      retrospectively gated cine images in sinus rhythm patients. With an exposure time
      of 95.2 ms and a frame rate of > 89 frames per second, golden-angle real-time
      imaging accurately captures hemodynamic function over a range of patient heart
      rates. In four patients with frequent ectopic contractions, initial
      quantification of the impact of ectopic beats on hemodynamic function was
      demonstrated. CONCLUSION: User-initialized active contours and golden-angle real
      time radial CMR can be used to determine time-varying LV function in patients.
      These methods will be very useful for the assessment of LV function in patients
      with frequent arrhythmias.

PMID- 25994393
TI  - Three-dimensional patterning of solid microstructures through laser reduction of
      colloidal graphene oxide in liquid-crystalline dispersions.
AB  - Graphene materials and structures have become an essential part of modern
      electronics and photovoltaics. However, despite many production methods,
      applications of graphene-based structures are hindered by high costs, lack of
      scalability and limitations in spatial patterning. Here we fabricate three
      dimensional functional solid microstructures of reduced graphene oxide in a
      lyotropic nematic liquid crystal of graphene oxide flakes using a pulsed near
      infrared laser. This reliable, scalable approach is mask-free, does not require
      special chemical reduction agents, and can be implemented at ambient conditions
      starting from aqueous graphene oxide flakes. Orientational ordering of graphene
      oxide flakes in self-assembled liquid-crystalline phases enables laser patterning
      of complex, three-dimensional reduced graphene oxide structures and colloidal
      particles, such as trefoil knots, with 'frozen' orientational order of flakes.
      These structures and particles are mechanically rigid and range from hundreds of
      nanometres to millimetres in size, as needed for applications in colloids,
      electronics, photonics and display technology. 

PMID- 25994394
TI  - Mycosis fungoides associated with splenic infarction and muscle involvement.

PMID- 25994395
TI  - [Investigation of the columnar carbon-scatterer length for X-ray spectral
      measurement on 320-slice computed tomography].
AB  - A short length scatterer is adopted to measure the X-ray spectrum of computed
      tomography (CT) equipment with a wide irradiation field in the body axis
      direction. The purpose of this study is to compare X-ray spectra measured using
      different length scatterers and determine the most appropriate length for the
      scatterer. 320-slice CT equipment (Aquilion ONE) was used in this study. Circular
      carbonrods (3 cm diameter) with five different lengths (1-16 cm) were used as
      scatterers. The effect of the beam hardening phenomenon from different length
      carbon rods was evaluated according to the effective energy. The measurement
      accuracy for photon information was also evaluated based on the photon count
      corresponding to the characteristic X-ray. As a result, the beam hardening effect
      was scarcely observed when the 1 cm long scatterer was used, and the number of
      the photons measured for the characteristic X-ray was the most. Therefore, it was
      concluded that the 1 cm long circular carbon rod scatterer was the most suitable.

PMID- 25994396
TI  - [Examination of reducing misregistration for lower tube voltage of the mask image
      in CT angiography using subtraction method].
AB  - Computed tomographic angiography (CTA) has been used recently for the evaluation
      of intracerebral aneurysms, but it is difficult to use this technique to
      visualize aneurysms near the base of the skull because of the presence of bone.
      So, subtracted CTA has been used to separate vessels from bony structures.
      However, we see some misregistration when using subtraction method because of the
      patient moving, the disaccord of the X-ray tube orbit between the mask image and
      the live image, the expanding focus, and the bed bending. So, attentioning the
      difference of bone CT number in any tube voltages, we examined to make the image
      containing less misregistration by changing the tube voltage of mask image.
      Making a sham blood vessel, we examined the bone misregistration, the blood
      vessel volume, and the smoothness when changing the tube voltages of mask images.
      Comparing with 120 kV, as the tube voltage of the mask image was 80 kV, the bone
      misregistration decreased significantly, however the blood vessel volume
      decreased. As for the tube voltage of 100 kV, the bone misregistration decreased
      significantly, and the blood vessel volume and the smoothness were not
      significantly different so we could get coordinative image of 120 kV. When the
      tube voltage of the mask image becomes lower than that of the live image and the
      effective energy becomes different, the effect of misregistration is less. This
      method deals with changing the tube voltage only. So, it may be easy to make
      volume rendering (VR) image and this method may be used in every facility. 

PMID- 25994397
TI  - [Evaluation of the right internal iliac artery which is anastomosed to transplant
      renal artery using non-contrast enhanced MR angiography with electrocardiography
      gated and 3D True SSFP time-spatial labeling inversion pulse sequence].
AB  - To evaluate whether electrocardiography-gated is useful in non-contrast-enhanced
      MRA with time-spatial labeling inversion pulse (Time-SLIP) in renal
      transplantation patients compared with respiration-triggered free-breathing.
      Simulation-based analyses of black blood time interval (BBTI) values for spatial
      selective inversion-recovery pulse and electrocardiography rates were performed,
      and confirmed on human subjects using a three-dimensional (3D) coherent steady
      state free precession (SSFP) sequence on a 1.5 tesla Toshiba MRI scanner. Signal
      acquisition interval and BBTI values in which signal of a water tissue becomes
      the null point showed a strong correlation, and successfully suppressed signals
      from the background and provided better contrast between the arteries and the
      background. Because electrocardiography-gated non-contrast MRA does not depend on
      the respiration interval, providing a contrast stable, it was suggested to be an
      effective screening tool for evaluation of pelvic arteries. 

PMID- 25994398
TI  - [What radiologists require in head CT].

PMID- 25994399
TI  - [Diagnosis reference levels and medical radiation protection].

PMID- 25994400
TI  - [9. Application of the Monte Carlo simulation 6: Monte Carlo simulation in
      nuclear medicine].

PMID- 25994401
TI  - [6. Diagnostic imaging for brain tumor].

PMID- 25994402
TI  - [Electrical and loading characteristics of X-ray tube assemblies for medical
      diagnosis].

PMID- 25994403
TI  - [Participation/dispatch reports on international conferences in 2014].

PMID- 25994404
TI  - [Security of external storage of healthcare information].

PMID- 25994406
TI  - New insights in Staphylococcus pseudintermedius pathogenicity: antibiotic
      resistant biofilm formation by a human wound-associated strain.
AB  - BACKGROUND: Staphylococcus pseudintermedius is an opportunistic pathogen
      recognized as the leading cause of skin, ear, and post-operative bacterial
      infections in dogs and cats. Zoonotic infections have also recently been reported
      causing endocarditis, infection of surgical wounds, rhinosinusitis, and catheter
      related bacteremia. The aim of the present study is to evaluate, for the first
      time, the pathogenic potential of S. pseudintermedius isolated from a human
      infection. To this end, strain DSM 25713, which was recently isolated from a
      wound of a leukemic patient who underwent a bone marrow transplantation, was
      investigated for biofilm formation and antibiotic-resistance under conditions
      relevant for wound infection. RESULTS: The effect of pH (5.5, 7.1, and 8.7) and
      the presence of serum (diluted at 1:2, 1:10, and 1:100) on biofilm formation was
      assessed through a crystal violet assay. The presence of serum significantly
      reduced the ability to form biofilm, regardless of the pH value tested. In vitro
      activity of eight antibiotics against biofilm formation and mature 48 h-old
      biofilms was comparatively assessed by crystal violet assay and viable cell
      count, respectively. Antibiotics at sub-inhibitory concentrations reduced biofilm
      formation in a dose-dependent manner, although cefoxitin was the most active,
      causing a significant reduction already at 1/8xMIC. Rifampicin showed the highest
      activity against preformed biofilms (MBEC90: 2xMIC). None of the antibiotics
      completely eradicated the preformed biofilms, regardless of tested
      concentrations. Confocal and electron microscopy analyses of mature biofilm
      revealed a complex "mushroom-like" architecture consisting of microcolonies
      embedded in a fibrillar extracellular matrix. CONCLUSIONS: For the first time,
      our results show that human wound-associated S. pseudintermedius is able to form
      inherently antibiotic-resistant biofilms, suggestive of its pathogenic potential,
      and consistent with recent reports of zoonotic infections.

PMID- 25994407
TI  - Mismatch of presenting symptoms at first and recurrent acute myocardial
      infarction. From the MONICA/KORA Myocardial Infarction Registry.
AB  - BACKGROUND: It is unknown whether the symptoms of first and recurrent acute
      myocardial infarction (AMI) are similar in the same person. This study examined
      the frequency of symptom mismatch, which factors are associated with a symptom
      mismatch and how symptom mismatch is related to 28-day case fatality. DESIGN:
      Observational study. METHODS: The sample consisted of 1282 persons with a first
      and recurrent AMI, recruited from a population-based AMI registry, 1985-2011.
      Occurrence of 11 symptoms was recorded in first and recurrent AMI using
      standardized patient interview. Logistic regression modelling adjusted for
      demographic and clinical variables was applied. RESULTS: Mismatch was highest for
      dyspnoea (40.6%) and lowest for chest symptoms (10.4%). Compared with women, men
      were less likely to have a mismatch of pain between the shoulder blades (odds
      ratio (OR) 0.58, 95% confidence interval (CI) 0.43-0.79), pain in the throat/jaw
      (OR 0.67, 95% CI 0.50-0.91), nausea (OR 0.62, 95% CI 0.47-0.82), vomiting (OR
      0.50, 95% CI 0.36-0.71), or fear of death (OR 0.71, 95% CI 0.53-0.94), or to have
      three or more mismatching symptoms (OR 0.60, 95% CI 0.45-0.79). Persons with
      diabetes were more likely to have a mismatch in chest symptoms, whereas persons
      with hyperlipidaemia or persons who received any revascularization therapy at
      first infarction were significantly less likely to have a mismatch of chest
      symptoms. Twenty-eight-day case fatality significantly increased with the number
      of mismatching symptoms (OR 1.14, 95% CI 1.02-1.28). CONCLUSIONS: Patients with
      AMI may benefit from information about the possibility that a recurrent
      infarction may be associated with different symptoms.

PMID- 25994408
TI  - Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase
      inhibitor resistant metastatic breast cancer.
AB  - Acquired estrogen receptor gene (ESR1) mutations have been recently reported as a
      marker of resistance to aromatase inhibitors in hormone receptor positive
      metastatic breast cancer. We retrospectively considered seven patients treated
      for metastatic breast cancer with available samples from the primary tumor before
      any treatment, cryopreserved metastasis removed during progression and
      concomitant plasmas. All these seven patients were in disease progression after
      previous exposure to aromatase inhibitors for at least 6 months, and were
      assessed for ESR1 mutations detection in tumor and circulating DNA. For these
      patients, Sanger sequencing identified four metastases with clear ESR1 mutation
      and one possible, whereas digital PCR identified six mutated metastases. Then,
      under blind conditions and using digital PCR, corresponding circulating ESR1
      mutations were successfully detected in four of these six metastatic breast
      cancer patients. Moreover, in two patients with serial blood samples following
      treatments exposure, the monitoring of circulating ESR1 mutations clearly
      predicted disease evolution. In the context of high interest for ESR1 mutations,
      our results highlight that these acquired recurrent mutations may be tracked in
      circulating tumor DNA and may be of clinical relevance for metastatic breast
      cancer patient monitoring. 

PMID- 25994409
TI  - Association between age at menarche and autistic traits in Turkish university
      students.
AB  - OBJECTIVES: The androgen theory of autism suggests that masculinizing effect of
      fetal androgens may play a role in the expression of autism. Recent evidence
      showed that excessive prenatal androgen exposure might delay age at menarche
      (AAM). The aim of this study was to investigate the relation between autistic
      traits and AAM in a sample of nonclinical female university students. METHODS:
      Autistic traits were measured using the Autism Spectrum Quotient (AQ), and AAM
      was questioned by retrospective self-reports. The AQ was completed by 436 female
      university students. RESULTS: There were significant positive correlations
      between AAM and AQ total and subscales measuring Social Skills, Communication,
      and Imagination. Subjects with above average autistic traits reported later AAM
      than subjects with below average autistic traits. CONCLUSION: These findings
      suggest that there may be a common developmental mechanism between delayed
      menarche and autistic traits, possibly through elevated levels of prenatal
      androgens.

PMID- 25994410
TI  - The influence of turbulence on the sensory basis of rheotaxis.
AB  - Rheotaxis is a widespread behavior with many potential benefits for fish and
      other aquatic animals, yet the sensory basis of rheotaxis under different fluvial
      conditions is still poorly understood. Here, we examine the role that vision and
      the lateral line play in the rheotactic behavior of a stream-dwelling species
      (Mexican tetra, Astyanax mexicanus) under both rectilinear and turbulent flow
      conditions. Turbulence lowered the flow speed at which threshold levels of
      rheotactic performance were elicited, an effect that was independent of sensory
      condition. Compared to fish with access to visual information, fish without
      access exhibited cross-stream casting behaviors and a decrease in the accuracy
      with which they oriented upstream. Visual deprivation effects were independent of
      availability of lateral line information and whether flow was rectilinear or
      turbulent. Fish deprived of lateral line information exhibited no measureable
      deficits under any of the conditions of this study. This study indicates that
      rheotactic abilities persist in the absence of both vision and lateral line under
      both turbulent and non-turbulent conditions, but that turbulence enhances either
      the motivation or ability of fish to orient to slow currents. 

PMID- 25994411
TI  - Atrial fibrillation is not associated with increased risk of venous
      thromboembolism: Results from ARAPACIS study.

PMID- 25994412
TI  - Alice M. Boring: a pioneer in the study of Chinese amphibians and reptiles.

PMID- 25994413
TI  - Insight into the antifungal mechanism of Neosartorya fischeri antifungal protein.
AB  - Small, cysteine-rich, highly stable antifungal proteins secreted by filamentous
      Ascomycetes have great potential for the development of novel antifungal
      strategies. However, their practical application is still limited due to their
      not fully clarified mode of action. The aim of this work was to provide a deep
      insight into the antifungal mechanism of Neosartorya fischeri antifungal protein
      (NFAP), a novel representative of this protein group. Within a short exposure
      time to NFAP, reduced cellular metabolism, apoptosis induction, changes in the
      actin distribution and chitin deposition at the hyphal tip were observed in NFAP
      sensitive Aspergillus nidulans. NFAP did show neither a direct membrane
      disrupting-effect nor uptake by endocytosis. Investigation of A. nidulans
      signalling mutants revealed that NFAP activates the cAMP/protein kinase A pathway
      via G-protein signalling which leads to apoptosis and inhibition of polar growth.
      In contrast, NFAP does not have any influence on the cell wall integrity pathway,
      but an unknown cell wall integrity pathway-independent mitogen activated protein
      kinase A-activated target is assumed to be involved in the cell death induction.
      Taken together, it was concluded that NFAP shows similarities, but also
      differences in its mode of antifungal action compared to two most investigated
      NFAP-related proteins from Aspergillus giganteus and Penicillium chrysogenum. 

PMID- 25994414
TI  - Protecting genes from RNA silencing by destroying aberrant transcripts.

PMID- 25994415
TI  - Distance measurements between manganese(II) and nitroxide spin-labels by DEER
      determine a binding site of Mn(2+) in the HP92 loop of ribosomal RNA.
AB  - Mn(2+) localization in hairpin 92 of the 23S ribosomal RNA (HP92) was obtained
      using W-band (95 GHz) DEER (double electron-electron resonance) distance
      measurements between the Mn(2+) ion and nitroxide spin labels on the RNA. It was
      found to be preferably situated in the minor groove of the double strand region
      close to the HP92 loop. 

PMID- 25994416
TI  - Assessment methods and prevalence of cognitive dysfunction in patients with low
      grade glioma: A systematic review.
AB  - OBJECTIVE: To systematically review the literature for studies on cognitive
      functioning in patients with low-grade glioma to evaluate assessment methods and
      prevalence of cognitive dysfunction. DATA SOURCES: A search was made in PubMed,
      Embase, and PsycINFO for articles published between January 2002 and June 2012
      using cognition, memory, attention, executive functioning, and low-grade glioma
      as search terms. STUDY SELECTION: Two reviewers independently performed the study
      selection and data extraction. Inclusion criteria were: studies including at
      least 10 adult patients, with suspected or confirmed low-grade glioma and
      cognitive functioning as outcome measure. DATA EXTRACTION: A standard data
      extraction form was used, with items regarding study quality, patient
      characteristics, type of measurement instruments, cognitive domain, definition of
      cognitive dysfunction, and reported prevalence. DATA SYNTHESIS: Of the 312
      articles screened on title/abstract, 69 were screened on full-text and, finally,
      17 were included. A total of 46 different measurement instruments were found for
      the assessment of cognitive functioning; 5 of these were used 5 or more times.
      There was variability in the definition of cognitive dysfunction. The reported
      prevalence of cognitive dysfunction ranged from 19% to 83%. CONCLUSION: Many
      patients with low-grade glioma experience cognitive dysfunction. However, there
      is no consensus on how to assess cognitive functioning in these patients.

PMID- 25994417
TI  - Gestational Weight Gain and Health Outcomes 18 Years Later in Urban Black Women.
AB  - OBJECTIVES: Excessive gestational weight gain (GWG) is associated with higher
      body mass index (BMI) later in life. Increased BMI is associated with health
      problems, but there is limited evidence linking GWG directly to later health in
      black women. We examined the association between GWG and health conditions 18
      years after a first birth. METHODS: This study was a secondary data analysis of
      467 urban black women, enrolled during pregnancy (1990-1991). GWG was the
      difference between self-reported pre-pregnancy weight and measured weight at
      delivery. Hypertension, diabetes, obesity, and self-reported health were assessed
      with self-report and measurements of blood pressure, height, and weight,
      approximately 18 years after first childbirth. RESULTS: Higher pre-pregnancy BMI
      was associated with increased probability of each health condition. Higher GWG
      was associated with hypertension for women with a pre-pregnancy BMI under 21.3
      kg/m(2) (P < .05) and obesity for women with a pre-pregnancy BMI under 25.9
      kg/m(2) (P < .05). Diabetes and poor health were not associated with GWG.
      CONCLUSIONS: GWG may impact a mother's hypertension and obesity status 18 years
      after childbirth for underweight and normal weight women.

PMID- 25994418
TI  - Prepregnancy Risk Factors for Preterm Birth and the Role of Maternal Nativity in
      a Low-Income, Hispanic Population.
AB  - OBJECTIVES: The aim of this study was to assess potential prepregnancy risk
      factors for preterm birth in a low-income, Hispanic population in Southern
      California. Additionally, the study assessed whether the prevalence of preterm
      birth and any associations between risk factors and preterm birth differed
      between U.S.- and foreign-born mothers. METHODS: The study sample included 1174
      mothers participating in the Special Supplemental Nutrition Program for Women,
      Infants and Children (WIC) within 1 year postpartum, including an augment sample
      of mothers who delivered preterm. Maternal sociodemographic traits, prepregnancy
      health-related characteristics and behaviors, and birth outcomes were collected
      by telephone survey. Odds ratios for associations between risk factors and
      preterm birth were estimated by logistic regression with sampling weights. Effect
      measure modification of any association by maternal nativity was also assessed
      using interaction terms. RESULTS: After adjustment for confounding, significant
      prepregnancy risk factors for preterm birth included maternal age >=35 years (OR
      2.00; 95 % CI 1.04, 3.84) compared to age 18-24 years, and experience of a
      financially stressful life event among U.S.-born, but not foreign-born, women (OR
      2.61; 95 % CI 1.43, 4.77). The weighted prevalence of preterm birth was 15.1 %
      and did not significantly differ by maternal nativity (P = 0.19). CONCLUSIONS FOR
      PRACTICE: Further investigation with large, prospective studies is needed to
      better understand the risk factors for and disparities in preterm birth among the
      growing Hispanic population in the U.S. so that women who are at risk
      prepregnancy can be identified and provided risk-specific services.

PMID- 25994419
TI  - Enantioseparation of the Six Important Intermediates of Homoharringtonine With
      Immobilized Cellulose Chiral Stationary Phase.
AB  - A new liquid chromatographic method has been developed for the chiral separation
      of the enantiomers of intermediates in the preparation of the ester side-chain of
      homoharringtonine. The enantiomers were separated by a Chiralpak IC (250 * 4.6
      mm, 5 um) in normal phase high-performance liquid chromatography (HPLC). Four
      compounds were baseline resolved. By comparing the chromatographs of racemates
      and single enantiomers of the six intermediates, the enantiomeric excess values
      of the single enantiomers were evaluated, and the elution orders of the
      enantiomers were established.

PMID- 25994421
TI  - Exposure of resident sparrows to West Nile virus evidenced in South Tunisia.
AB  - During the last few years, several cases of West Nile virus (WNV) infection in
      humans have been reported in Tunisia. However, detailed information on WNV
      infection in wild birds, the primary amplifying host of WNV, are lacking. In this
      work, we investigated the exposure of wild sparrows (hybrid Passer domesticus *
      hispaniolensis) living in two oases in southern Tunisia (Gabes and Kebili oases)
      to WNV, through the detection of WNV-specific antibodies by using ELISA and
      microneutralization tests. In total, 208 birds were sampled (54 from Kebili, 154
      from Gabes). Anti-WNV antibodies were detected in two birds, corresponding to an
      overall seroprevalence of 1%. There was no significant difference between the two
      sampled populations [1.85% (1/54) in Kebili, 0.65% (1/154) in Gabes]. These data
      provide indirect evidence of the exposure of resident sparrows in southern
      Tunisia to WNV. 

PMID- 25994422
TI  - Self-assembly of amphiphilic anionic calix[4]arenes and encapsulation of poorly
      soluble naproxen and flurbiprofen.
AB  - Supramolecular aggregates formed through the association of an amphiphilic tetra
      O-butylsulfonate calix[4]arene 1 were investigated in aqueous solution by a
      combination of different techniques (NMR, DLS and AFM). The ability of the
      micellar aggregates of calixarene 1 to increase the solubility of poorly water
      soluble drugs was studied. 

PMID- 25994420
TI  - The emerging role of senescent cells in tissue homeostasis and pathophysiology.
AB  - Cellular senescence is a state of permanent growth arrest and is thought to play
      a pivotal role in tumor suppression. Cellular senescence may play an important
      role in tumor suppression, wound healing, and protection against tissue fibrosis
      in physiological conditions in vivo. However, accumulating evidence that
      senescent cells may have harmful effects in vivo and may contribute to tissue
      remodeling, organismal aging, and many age-related diseases also exists. Cellular
      senescence can be induced by various intrinsic and extrinsic factors. Both
      p53/p21 and p16/RB pathways are important for irreversible growth arrest in
      senescent cells. Senescent cells secret numerous biologically active factors.
      This specific secretion phenotype by senescent cells may largely contribute to
      physiological and pathological consequences in organisms. Here I review the
      molecular basis of cell cycle arrest and the specific secretion phenotype in
      cellular senescence. I also summarize the current knowledge of the role of
      cellular senescence in vivo in physiological and pathological settings. 

PMID- 25994423
TI  - Ethnic disparity in the clinical characteristics of patients with heart failure.
AB  - AIMS: The characteristics of heart failure (HF) patients of different ethnic
      backgrounds in Israel are unknown. The purpose of the present study was to
      evaluate the clinical characteristics of Arab vs. Jewish patients with chronic
      HF. METHODS AND RESULTS: Patients with a diagnosis of HF at a health maintenance
      organization in Jerusalem, Israel were evaluated. All patients were followed for
      cardiac-related hospitalizations and death. The study cohort included 6773 HF
      patients; 4991 (74%) were Jewish and 1735 (26%) were Arab. The overall prevalence
      of HF in the Jewish vs. Arab population was similar (women, 4.3% vs. 4.7%,
      respectively, P = 0.06; men, 5.3% vs. 5.2%, P = 0.61). The prevalence of HF was
      significantly higher in Arab subjects of younger age groups (50-70 years). Arabs
      developed HF on average 10 years earlier and had a significantly higher rate of
      diabetes and obesity. Standard of care based on prescribed medications was
      similar between the ethnic groups. Glucose and cholesterol levels were higher in
      the Arab cohort. Mortality was similar between the groups at median follow-up
      (576 days), with the exception of cardiovascular hospitalizations and death that
      were higher in Arab men. CONCLUSIONS: Arab subjects develop HF at a much younger
      age compared with their Jewish counterparts and have a higher prevalence of
      diabetes and obesity. Standard of care and clinical outcome are comparable.
      Implementation of prevention programmes to reduce risk factors, particularly
      diabetes and obesity, may help reduce the disparity between Arabs and Jews.

PMID- 25994424
TI  - A chromium precursor for the Phillips ethylene trimerization catalyst: (2
      ethylhexanoate)2CrOH.
AB  - The conventional Phillips ethylene trimerization catalyst prepared by reacting
      Cr(EH)3 (EH = 2-ethylhexanoate), 2,5-dimethylpyrrole (Me2C4H2NH), Et3Al, and
      Et2AlCl in an aromatic hydrocarbon solvent was improved to obtain a congener
      composed of a new chromium precursor (EH)2CrOH, (Me2C4H2N)AlEt2, and
      Et3Al.ClAlEt2. Reaction of CrCl3 with 3 equiv. Na(EH) in water did not generate
      Cr(EH)3, but unexpectedly produced (EH)2CrOH. In comparison with the erratic
      catalytic performance of the original Phillips system, due to the ill-defined
      nature of the Cr(EH)3 source (16 or 6.8 * 10(6) g per mol-Cr h depending on the
      source), the improved system exhibited consistently high activity (54 * 10(6) g
      per mol-Cr h). Reaction of (EH)2CrOH with (Me2C4H2N)AlMe2.OEt2 afforded the
      dimeric Cr(II)-complex (6) coordinated by (eta(5)-Me2C4H2N)AlMe2(NC4H2Me2) and
      MU2-kappa(1):eta(2)-Me2C4H2N ligands. 6 provided highly active species when
      activated with Et3Al.ClAlEt2.

PMID- 25994427
TI  - Successful direct amplification of nuclear markers from single dog hairs using
      DogFiler multiplex.
AB  - We report on successful amplification of canine STR DNA profiles from single dog
      hairs. Dog hairs are commonly found on clothing or items of interest in forensic
      casework and may be crucial associative evidence if linked to an individual dog.
      We used direct amplification from these hairs to increase the DNA yield of the
      sample, as well as greatly reducing analysis time. Hairs from different somatic
      regions were used from several different dog breeds to amplify a selection of
      eight loci from the validated DogFiler multiplex. Naturally shed canine hairs
      were processed, with a mix of coarse topcoat (guard) hairs and thinner soft
      undercoat hairs. Multiple sections of single hairs were amplified in 5 mm
      segments to determine the viability of DNA recovery from the shaft of the hair.
      Single guard hairs were cut into 5 mm sections and added directly into a PCR
      tube. Undercoat hairs, which are very fine, were amplified together in a single
      tube (approximately ten small hairs). Coarse hairs were found to be the most
      successful in producing full DNA profiles at all eight loci, matching the
      corresponding reference profile for that dog. 

PMID- 25994426
TI  - Comparative use of the computer-aided angiography and rapid prototyping
      technology versus conventional imaging in the management of the Tile C pelvic
      fractures.
AB  - INTRODUCTION: Computed tomography (CT) scan with three-dimensional (3D)
      reconstruction has been used to evaluate complex fractures in pre-operative
      planning. In this study, rapid prototyping of a life-size model based on 3D
      reconstructions including bone and vessel was applied to evaluate the feasibility
      and prospect of these new technologies in surgical therapy of Tile C pelvic
      fractures by observing intra- and perioperative outcomes. MATERIALS AND METHODS:
      The authors conducted a retrospective study on a group of 157 consecutive
      patients with Tile C pelvic fractures. Seventy-six patients were treated with
      conventional pre-operative preparation (A group) and 81 patients were treated
      with the help of computer-aided angiography and rapid prototyping technology (B
      group). Assessment of the two groups considered the following perioperative
      parameters: length of surgical procedure, intra-operative complications, intra-
      and postoperative blood loss, postoperative pain, postoperative nausea and
      vomiting (PONV), length of stay, and type of discharge. RESULTS: The two groups
      were homogeneous when compared in relation to mean age, sex, body weight, injury
      severity score, associated injuries and pelvic fracture severity score. Group B
      was performed in less time (105 +/- 19 minutes vs. 122 +/- 23 minutes) and blood
      loss (31.0 +/- 8.2 g/L vs. 36.2 +/- 7.4 g/L) compared with group A. Patients in
      group B experienced less pain (2.5 +/- 2.3 NRS score vs. 2.8 +/- 2.0 NRS score),
      and PONV affected only 8 % versus 10 % of cases. Times to discharge were shorter
      (7.8 +/- 2.0 days vs. 10.2 +/- 3.1 days) in group B, and most of patients were
      discharged to home. CONCLUSIONS: In our study, patients of Tile C pelvic
      fractures treated with computer-aided angiography and rapid prototyping
      technology had a better perioperative outcome than patients treated with
      conventional pre-operative preparation. Further studies are necessary to
      investigate the advantages in terms of clinical results in the short and long
      run.

PMID- 25994428
TI  - Thyrotoxicosis: an under-recognised aetiology.
AB  - A 53-year-old woman presented for evaluation of dizziness, shortness of breath
      and chest pain. She was found to be in atrial fibrillation with rapid ventricular
      response that was determined to be caused by iodine-induced thyrotoxicosis (from
      a CT scan with intravenous contrast 2 months prior to presentation). Jod-Basedow
      syndrome (iodine-induced hyperthyroidism) is infrequently considered as a cause
      of thyrotoxicosis, even when typical risk factors are present. However, this
      patient did not have typical risk factors: she did not reside in an iodine
      deficient area, did not have a prior diagnosis of thyroid disorder or goitre, had
      never been treated with thyroid medications or medications known to cause thyroid
      dysfunction and she presented later than is typical with this syndrome (2 months
      after receiving iodinated contrast). She had complete resolution of
      hyperthyroidism and atrial fibrillation 2 weeks later with no recurrence over the
      following 7 months. 

PMID- 25994425
TI  - Manual lymphatic drainage for lymphedema following breast cancer treatment.
AB  - BACKGROUND: More than one in five patients who undergo treatment for breast
      cancer will develop breast cancer-related lymphedema (BCRL). BCRL can occur as a
      result of breast cancer surgery and/or radiation therapy. BCRL can negatively
      impact comfort, function, and quality of life (QoL). Manual lymphatic drainage
      (MLD), a type of hands-on therapy, is frequently used for BCRL and often as part
      of complex decongestive therapy (CDT). CDT is a fourfold conservative treatment
      which includes MLD, compression therapy (consisting of compression bandages,
      compression sleeves, or other types of compression garments), skin care, and
      lymph-reducing exercises (LREs). Phase 1 of CDT is to reduce swelling; Phase 2 is
      to maintain the reduced swelling. OBJECTIVES: To assess the efficacy and safety
      of MLD in treating BCRL. SEARCH METHODS: We searched Medline, EMBASE, CENTRAL,
      WHO ICTRP (World Health Organization's International Clinical Trial Registry
      Platform), and Cochrane Breast Cancer Group's Specialised Register from root to
      24 May 2013. No language restrictions were applied. SELECTION CRITERIA: We
      included randomized controlled trials (RCTs) or quasi-RCTs of women with BCRL.
      The intervention was MLD. The primary outcomes were (1) volumetric changes, (2)
      adverse events. Secondary outcomes were (1) function, (2) subjective sensations,
      (3) QoL, (4) cost of care. DATA COLLECTION AND ANALYSIS: We collected data on
      three volumetric outcomes. (1) LE (lymphedema) volume was defined as the amount
      of excess fluid left in the arm after treatment, calculated as volume in mL of
      affected arm post-treatment minus unaffected arm post-treatment. (2) Volume
      reduction was defined as the amount of fluid reduction in mL from before to after
      treatment calculated as the pretreatment LE volume of the affected arm minus the
      post-treatment LE volume of the affected arm. (3) Per cent reduction was defined
      as the proportion of fluid reduced relative to the baseline excess volume,
      calculated as volume reduction divided by baseline LE volume multiplied by 100.
      We entered trial data into Review Manger 5.2 (RevMan), pooled data using a fixed
      effect model, and analyzed continuous data as mean differences (MDs) with 95%
      confidence intervals (CIs). We also explored subgroups to determine whether mild
      BCRL compared to moderate or severe BCRL, and BCRL less than a year compared to
      more than a year was associated with a better response to MLD. MAIN RESULTS: Six
      trials were included. Based on similar designs, trials clustered in three
      categories.(1) MLD + standard physiotherapy versus standard physiotherapy (one
      trial) showed significant improvements in both groups from baseline but no
      significant between-groups differences for per cent reduction.(2) MLD +
      compression bandaging versus compression bandaging (two trials) showed
      significant per cent reductions of 30% to 38.6% for compression bandaging alone,
      and an additional 7.11% reduction for MLD (MD 7.11%, 95% CI 1.75% to 12.47%; two
      RCTs; 83 participants). Volume reduction was borderline significant (P = 0.06).
      LE volume was not significant. Subgroup analyses was significant showing that
      participants with mild-to-moderate BCRL were better responders to MLD than were
      moderate-to-severe participants.(3) MLD + compression therapy versus nonMLD
      treatment + compression therapy (three trials) were too varied to pool. One of
      the trials compared compression sleeve plus MLD to compression sleeve plus
      pneumatic pump. Volume reduction was statistically significant favoring MLD (MD
      47.00 mL, 95% CI 15.25 mL to 78.75 mL; 1 RCT; 24 participants), per cent
      reduction was borderline significant (P=0.07), and LE volume was not significant.
      A second trial compared compression sleeve plus MLD to compression sleeve plus
      self-administered simple lymphatic drainage (SLD), and was significant for MLD
      for LE volume (MD -230.00 mL, 95% CI -450.84 mL to -9.16 mL; 1 RCT; 31
      participants) but not for volume reduction or per cent reduction. A third trial
      of MLD + compression bandaging versus SLD + compression bandaging was not
      significant (P = 0.10) for per cent reduction, the only outcome measured (MD
      11.80%, 95% CI -2.47% to 26.07%, 28 participants).MLD was well tolerated and safe
      in all trials.Two trials measured function as range of motion with conflicting
      results. One trial reported significant within-groups gains for both groups, but
      no between-groups differences. The other trial reported there were no significant
      within-groups gains and did not report between-groups results. One trial measured
      strength and reported no significant changes in either group.Two trials measured
      QoL, but results were not usable because one trial did not report any results,
      and the other trial did not report between-groups results.Four trials measured
      sensations such as pain and heaviness. Overall, the sensations were significantly
      reduced in both groups over baseline, but with no between-groups differences. No
      trials reported cost of care.Trials were small ranging from 24 to 45
      participants. Most trials appeared to randomize participants adequately. However,
      in four trials the person measuring the swelling knew what treatment the
      participants were receiving, and this could have biased results. AUTHORS'
      CONCLUSIONS: MLD is safe and may offer additional benefit to compression
      bandaging for swelling reduction. Compared to individuals with moderate-to-severe
      BCRL, those with mild-to-moderate BCRL may be the ones who benefit from adding
      MLD to an intensive course of treatment with compression bandaging. This finding,
      however, needs to be confirmed by randomized data.In trials where MLD and sleeve
      were compared with a nonMLD treatment and sleeve, volumetric outcomes were
      inconsistent within the same trial. Research is needed to identify the most
      clinically meaningful volumetric measurement, to incorporate newer technologies
      in LE assessment, and to assess other clinically relevant outcomes such as
      fibrotic tissue formation.Findings were contradictory for function (range of
      motion), and inconclusive for quality of life.For symptoms such as pain and
      heaviness, 60% to 80% of participants reported feeling better regardless of which
      treatment they received.One-year follow-up suggests that once swelling had been
      reduced, participants were likely to keep their swelling down if they continued
      to use a custom-made sleeve.

PMID- 25994429
TI  - Combined acromioclavicular joint dislocation and coracoid avulsion in an adult.
AB  - Avulsion fracture of coracoid process with acromioclavicular joint dislocation is
      extremely rare. We report a case of coracoid avulsion with acromioclavicular
      disruption in a 24-year-old man who sustained injuries in a road traffic
      accident. Although acromioclavicular (AC) dislocation was obvious from an initial
      radiograph, coracoid avulsion was picked up in a CT scan. Open reduction and
      internal fixations of the coracoid with a 4 mm cannulated screw, an AC joint with
      two K-wires and an anchor suture, resulted in rapid recovery. The patient had
      complete range of shoulder movements at the end of 3 months and he resumed his
      professional activities. After 1 year, he had normal shoulder movement without
      any functional limitations.

PMID- 25994430
TI  - Management of pregnancy after augmentation cystoplasty.
AB  - We report a case of successful pregnancy following augmentation ileocystoplasty
      in a patient with a neurogenic bladder dysfunction. A review of the literature
      reveals incidences of premature delivery and renal dysfunction. Careful
      urological monitoring of such patients should result in a successful pregnancy.
      Nevertheless, the unique clinical challenges and management options published to
      date are limited. 

PMID- 25994431
TI  - Breast cancer in male-to-female (MtF) transgender patients: is hormone receptor
      negativity a feature?
AB  - A 41-year-old male-to-female (MtF) transgender patient presented with a
      symptomatic tender lump in the left breast. There was no family history of breast
      cancer. She had been receiving estrogen therapy for 14 years to maintain her
      secondary sexual characteristics. Triple assessment revealed a 13 mm triple
      negative grade 3 invasive ductal carcinoma. The tumour was completely excised
      following a left wide local excision and sentinel lymph node biopsy. There was no
      regional lymph node involvement. She was referred to the oncologist for adjuvant
      chemotherapy and radiotherapy. 

PMID- 25994432
TI  - Fishbone-induced perforated appendicitis.
AB  - We review the literature and describe a case of fishbone-induced appendicitis. A
      63-year-old man presented with abdominal pain. Work up including a focused
      history and imaging revealed fishbone-induced perforated appendicitis. The
      patient was managed safely and successfully with laparoscopic removal of the
      foreign body and appendectomy. 

PMID- 25994433
TI  - Psoas muscle pyogenic abscess in association with infected hip arthroplasty: a
      rare case of simultaneous bilateral presentation.
AB  - Simultaneous bilateral presentation of psoas abscess with prosthetic joint
      involvement is extremely rare. A 68-year-old woman presented to us with bilateral
      dull aching groin pain of 6 months' duration, which flared up in the past month,
      associated with pyrexial symptoms. She had undergone bilateral hip replacements
      in the past with uneventful recovery. MRI showed bilateral psoas muscle
      collection in communication with the hip joints. Preoperative hip aspirate
      demonstrated frank pus with positivity on Gram stain and radiographs confirmed
      prosthetic loosening of bilateral hips. The patient subsequently underwent two
      stage revision arthroplasty of both infected hip implants. At 5-year follow-up,
      the patient remains asymptomatic with good functional outcome and no recurrence
      on serial MRI. 

PMID- 25994434
TI  - Radial shaft stress fracture after internal fixation using a titanium plate.
AB  - A 22-year-old man, a boxer, presented with acute right forearm pain after
      striking a punch mitt. The patient had sustained a diaphyseal fracture of the
      right radius 19 months previously and was treated by minimally invasive plate
      osteosynthesis using a titanium reconstruction plate. Radiography revealed stress
      fractures beneath a proximal screw hole of the plate. The forearm was protected
      in a splint for 6 weeks and the fracture healed. Titanium plates are superior to
      stainless steel plates, due to various properties of titanium including corrosion
      resistance and biocompatibility. Removal of such plates is not routinely
      performed in our hospital, but plate removal may be warranted for patients who
      actively participate in certain sports. 

PMID- 25994435
TI  - Unilateral testicular metastasis of low PSA level prostatic adenocarcinoma.
AB  - A 71-year-old man presented with a firm left testicle 15 years after being
      diagnosed with prostatic adenocarcinoma. After the initial diagnosis, the patient
      underwent a radical prostatectomy. He received radiation therapy 5 years after
      surgery for a slightly elevated prostate-specific antigen (PSA) level and a
      negative metastatic workup. Eight years later, the patient's PSA rose to 3.38
      ng/mL and he was started on intermittent Lupron therapy. It was then 3 years
      later when the patient discovered the testicular mass. At that time, his PSA
      level was 2.98 ng/mL. He underwent a left orchiectomy which demonstrated
      metastatic prostatic adenocarcinoma. Currently, the patient is doing well 3
      months postorchiectomy and is now receiving continuous testosterone suppression
      therapy. This case report discusses the unique modes of spread from the prostate
      to the testicle as well as the importance of follow-up care in patients with
      prostate cancer, especially in the setting of low PSA levels. 

PMID- 25994436
TI  - Fresh arterial homograft for bypass in critical limb ischaemia with infection.
AB  - We present what we believe is Australia's first fresh peripheral arterial
      transplant for revascularisation of an ischaemic limb. Although cryopreserved
      homografts are accepted as a management option for revascularisation of critical
      limb ischaemia in infected fields, cryopreserved peripheral vascular tissue is
      not currently available in Australia. We describe a 72-year-old man without
      autologous conduit in whom infected prosthetic grafts were explanted, causing
      critical limb ischaemia of a below knee stump. Fresh peripheral arterial tissue
      was procured via the Australian organ donation authority, DonateLife, and was
      used to revascularise the stump with an axillofemoral bypass. This permitted
      successful healing of the stump within 6 weeks and mobilisation with a
      prosthesis. This case illustrates that fresh arterial homografts are a viable
      bridging solution for revascularisation of limb ischaemia with infection.
      However, it also highlights the need to establish a peripheral homograft bank so
      that cryopreserved conduits are readily available for similar scenarios. 

PMID- 25994437
TI  - Migrating foreign bodies in the upper aerodigestive tract: a surgical challenge.
AB  - Migrating foreign bodies in the aerodigestive tract are uncommon but can pose
      serious complications. Long-standing migrating foreign bodies can exist
      manifesting chronic and unusual symptoms such as chronic cough, recurrent
      episodes of dyspnoea and fever. Adverse body reactions to foreign objects such as
      adhesions can cause difficulty in their diagnosis, localisation and removal. A
      thorough clinical and radiographical approach is of immense value in such cases.
      We report two difficult cases of migrated foreign bodies: a 2-year-old child with
      a long-standing foreign body that migrated to the upper mediastinum, and an adult
      patient with a fish bone that migrated to the oropharyngeal muscles.
      Presentations of these cases were not alike, with chronic unusual recurrent
      symptoms in one and typical acute symptoms in the other. The diagnosis and
      precise localisation of both foreign bodies was challenging, and an open approach
      was employed to remove them. 

PMID- 25994438
TI  - Defining the links between oxidative stress-based biomarkers and postoperative
      atrial fibrillation.

PMID- 25994440
TI  - Joint Effect of Hypertension and Elevated Serum Phosphorus on the Risk of
      Mortality in National Health and Nutrition Examination Survey-III.
AB  - BACKGROUND: Elevated serum phosphorus might aggravate the effect of hypertension
      on mortality. The objective of this study was to examine the joint effect of
      hypertension and serum phosphorus on the risk of mortality. METHODS AND RESULTS:
      A large prospective (n=15 833), population-based cohort of participants from the
      National Health and Nutritional Examination Survey III was examined to test
      potential synergism between hypertension, elevated serum phosphorus, and the risk
      of mortality. Interaction on additive scale and multiplicative scale was
      estimated. After a median follow-up of 14.3 years, 1691 cases of cardiovascular
      mortality and 3875 cases of all-cause mortality were identified. Interaction was
      observed between hypertension and elevated serum phosphorus on the additive scale
      for cardiovascular mortality (relative excess risk due to interaction, 0.99, 95%
      CI: 0.06; 1.92, adjusted for age, gender, race, and estimated glomerular
      filtration rate). No statistically significant interaction was found between
      hypertension and serum phosphorus for all-cause mortality on the additive scale.
      No significant interaction was detected on the multiplicative scale. In
      sensitivity analysis, excluding participants who died in first 2 years and
      adjustment for additional confounders resulted in essentially similar findings.
      CONCLUSIONS: The joint effect of hypertension and elevated serum phosphorus was
      larger than the sum of the independent effects on cardiovascular mortality but
      not on all-cause mortality. Future studies should investigate whether controlling
      elevated serum phosphorus in hypertensive individuals helps in prevention of
      extra risk of cardiovascular mortality.

PMID- 25994439
TI  - Associations of blood pressure in pregnancy with offspring blood pressure
      trajectories during childhood and adolescence: findings from a prospective study.
AB  - BACKGROUND: Hypertensive disorders of pregnancy are related to higher offspring
      blood pressure (BP), but it is not known whether this association strengthens or
      weakens as BP changes across childhood. Our aim was to assess the associations of
      hypertensive disorders of pregnancy and maternal BP changes during pregnancy with
      trajectories of offspring BP from age 7 to 18 years. METHODS AND RESULTS: In a
      large UK cohort of maternal-offspring pairs (N=6619), we used routine antenatal
      BP measurements to derive hypertensive disorders of pregnancy and maternal BP
      trajectories. These were related to offspring BP trajectories, obtained from
      research clinic assessments, using linear spline random-effects models. After
      adjusting for maternal and offspring variables, including body mass index,
      offspring of women who had existing hypertension, gestational hypertension, or
      preeclampsia during pregnancy had on average higher BP at age 7 years compared to
      offspring of normotensive pregnancies (mean difference [95%CI] in systolic BP:
      1.67 mm Hg [0.48, 2.86], 1.98 mm Hg [1.32, 2.65], and 1.22 mm Hg [-0.52, 2.97],
      respectively). These differences were consistent across childhood to age 18
      years, as the patterns of BP change did not differ between offspring of
      hypertensive pregnancies and normotensive pregnancies. Maternal BP at 8 weeks'
      gestation was also positively associated with offspring BP in childhood and
      adolescence, but changes in BP across pregnancy were not strongly associated.
      CONCLUSIONS: The differences in BP between offspring of hypertensive pregnancies
      and offspring of normotensive pregnancies remain consistent across childhood and
      adolescence. These associations appear to be most contributed to by higher
      maternal BP in early pregnancy rather than by pregnancy-related BP changes.

PMID- 25994441
TI  - Reactivity to the p305 Epitope of the alpha1G T-Type Calcium Channel and
      Autoimmune-Associated Congenital Heart Block.
AB  - BACKGROUND: Only 2% of mothers positive for anti-SSA/Ro (Ro) antibodies have
      children with congenital heart block (CHB). This study aimed to determine whether
      reactivity with p305, an epitope within the alpha1G T-type calcium channel,
      confers added risk over anti-Ro antibodies. METHODS AND RESULTS: Using sera from
      anti-Ro-exposed pregnancies resulting in offspring with CHB, no disease but CHB
      sibling, and no disease and no CHB-sibling, as well as disease (lupus without
      anti-Ro) and healthy controls, reactivities were determined for binding to Ro60,
      p305, and an epitope within Ro60, p133-Ro60, which shares structural properties
      with p305, including key amino acids and an alpha-helical structure. Candidate
      peptides were further evaluated in an in vitro model that assessed the binding of
      maternal antibodies to apoptotic cells. In anti-Ro-positive mothers, anti-p305
      autoantibodies (>3 SD above healthy controls) were detected in 3/59 (5%) CHB
      pregnancies, 4/30 (13%) unaffected pregnancies with a CHB-sibling, and 0/42 (0%)
      of unaffected pregnancies with no CHB-sibling. For umbilical bloods (61 CHB, 41
      healthy with CHB sibling), no association of anti-p305 with outcome was detected;
      however, overall levels of anti-p305 were elevated compared to mothers during
      pregnancy in all groups studied. For anti-p133-Ro60, reactivity paralleled that
      of anti-p305. In the screen employing apoptotic cells, p133-Ro60, but not p305,
      significantly attenuated the binding of immunoglobulin G isolated from a mother
      whose child had CHB (42.1% reduced to 13.9%, absence/presence of p133-Ro60,
      respectively, P<0.05). CONCLUSIONS: These data suggest that anti-p305 is not a
      robust maternal marker for assessing increased risk of CHB during an anti-SSA/Ro
      pregnancy.

PMID- 25994442
TI  - Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in
      the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation
      (OPERA) Trial.
AB  - BACKGROUND: Animal study results point to oxidative stress as a key mechanism
      triggering postoperative atrial fibrillation (PoAF), yet the extent to which
      specific biomarkers of oxidative stress might relate to PoAF risk in humans
      remains speculative. METHODS AND RESULTS: We assessed the association of
      validated, fatty acid-derived oxidative stress biomarkers (F2-isoprostanes,
      isofurans, and F3-isoprostanes) in plasma and urine, with incident PoAF among 551
      cardiac surgery patients. Biomarkers were measured at enrollment, the end of
      surgery, and postoperative day 2. PoAF lasting >=30 seconds was confirmed with
      rhythm strip or electrocardiography and centrally adjudicated. Outcomes were
      assessed until hospital discharge or postoperative day 10, whichever occurred
      first. Urine level of each oxidative stress biomarker rose at the end of surgery
      (2- to 3-fold over baseline, P<0.001) and subsequently declined to concentrations
      comparable to baseline by postoperative day 2. In contrast, plasma concentrations
      remained relatively stable throughout the perioperative course. Urine F2
      isoprostanes and isofurans at the end of surgery were 20% and 50% higher in
      subjects who developed PoAF (P<=0.009). While baseline biomarker levels did not
      associate significantly with PoAF, end of surgery and postoperative day 2
      isoprostanes and isofurans demonstrated relatively linear associations with PoAF.
      For example, the end of surgery extreme quartile multivariate adjusted OR (95%
      CI) for urine isofurans and F3-isoprostanes were 1.95 (1.05 to 3.62; P for
      trend=0.01) and 2.10 (1.04 to 2.25, P for trend=0.04), respectively. The
      associations of biomarkers with PoAF varied little by demographics, surgery type,
      and medication use (P>=0.29 for each). CONCLUSIONS: These novel results add to
      accumulating evidence supporting the likely key pathogenic role of elevated
      oxidative stress in PoAF. CLINICAL TRIAL REGISTRATION: URL: Clinicaltrials.gov
      Unique identifier: NCT00970489.

PMID- 25994443
TI  - Increased stiffness is the major early abnormality in a pig model of severe
      aortic stenosis and predisposes to congestive heart failure in the absence of
      systolic dysfunction.
AB  - BACKGROUND: It remains unclear whether abnormal systolic function and relaxation
      are essential for developing heart failure in pathophysiology of severe aortic
      stenosis. METHODS AND RESULTS: Yorkshire pigs underwent surgical banding of the
      ascending aorta. The animals were followed for up to 5 months after surgery, and
      cardiac function was assessed comprehensively by invasive pressure-volume
      measurements, 3-dimensional echocardiography, echocardiographic speckle-tracking
      strain, and postmortem molecular and histological analyses. Pigs with aortic
      banding (n=6) exhibited significant left ventricular hypertrophy with increased
      stiffness compared with the control pigs (n=7) (end-diastolic pressure-volume
      relationship beta: 0.053+/-0.017 versus 0.028+/-0.009 mm Hg/mL, P=0.007);
      however, all other parameters corresponding to systolic function, including
      ejection fraction, end-systolic pressure-volume relationship, preload recruitable
      stroke work, echocardiographic circumferential strain, and longitudinal strain,
      were not impaired in pigs with aortic banding. Relaxation parameters were also
      similar between groups. Sarcoplasmic reticulum calcium (Ca(2+)) ATPase protein
      levels in the left ventricle were similar. There were significant increases in 3
      dimensional echocardiographic left atrial volumes, suggesting the usefulness of
      these indexes to detect increased stiffness. Right atrial pacing with a heart
      rate of 120 beats per minute induced increased end-diastolic pressure in pigs
      with aortic banding in contrast to decreased end-diastolic pressure in the
      control pigs. Histological evaluation revealed that increased stiffness was
      accompanied by cardiomyocyte hypertrophy and increased perimysial and
      perivascular fibrosis. CONCLUSION: Increased stiffness is the major early
      pathological process that predisposes to congestive heart failure without
      abnormalities in systolic function and relaxation in a clinically relevant animal
      model of aortic stenosis.

PMID- 25994444
TI  - Cardiovascular Disease Performance Measures in the Outpatient Setting in India:
      Insights From the American College of Cardiology's PINNACLE India Quality
      Improvement Program (PIQIP).
AB  - BACKGROUND: India has a growing burden of cardiovascular disease (CVD), yet data
      on the quality of outpatient care for patients with coronary artery disease,
      heart failure, and atrial fibrillation in India are very limited. We collected
      data on performance measures for 68 196 unique patients from 10 Indian cardiology
      outpatient departments from January 1, 2011, to February 5, 2014, in the American
      College of Cardiology's PINNACLE (Practice Innovation and Clinical Excellence)
      India Quality Improvement Program (PIQIP). PIQIP is India's first national
      outpatient CVD quality-improvement program. METHODS AND RESULTS: In the PIQIP
      registry, we estimated the prevalence of CVD risk factors (hypertension,
      diabetes, dyslipidemia, and current tobacco use) and CVD among outpatients. We
      examined adherence with performance measures established by the American College
      of Cardiology, the American Heart Association, and the American Medical
      Association Physician Consortium for Performance Improvement for coronary artery
      disease, heart failure, and atrial fibrillation. There were a total of 68 196
      patients (155 953 patient encounters), with a mean age of 50.6 years (SD 18.2
      years). Hypertension was present in 29.7% of patients, followed by diabetes
      (14.9%), current tobacco use (7.6%), and dyslipidemia (6.5%). Coronary artery
      disease was present in 14.8%, heart failure was noted in 4.0%, and atrial
      fibrillation was present in 0.5% of patients. Among eligible patients, the
      reported use of medications was as follows: aspirin in 48.6%, clopidogrel in
      37.1%, and statin-based lipid-lowering therapy in 50.6% of patients with coronary
      artery disease; RAAS (renin-angiotensin-aldosterone system) antagonist in 61.9%
      and beta-blockers in 58.1% of patients with heart failure; and oral
      anticoagulants in 37.0% of patients with atrial fibrillation. CONCLUSIONS: This
      pilot study, initiated to improve outpatient CVD care in India, presents our
      preliminary results and barriers to data collection and demonstrates that such an
      initiative is feasible in a resource-limited environment. In addition, we
      attempted to outline areas for further improvement in outpatient CVD care
      delivery in India.

PMID- 25994445
TI  - Unsupervised exercise and mobility loss in peripheral artery disease: a
      randomized controlled trial.
AB  - BACKGROUND: Few medical therapies improve lower extremity functioning in people
      with lower extremity peripheral artery disease (PAD). Among people with PAD, we
      studied whether a group-mediated cognitive behavioral intervention promoting home
      based unsupervised exercise prevented mobility loss and improved functional
      performance compared to control. METHODS AND RESULTS: One hundred ninety-four PAD
      participants were randomized. During months 1 to 6, the intervention group met
      weekly with other PAD participants and a facilitator. Group support and self
      regulatory skills were used to help participants adhere to walking exercise.
      Ninety-percent of exercise was conducted at or near home. The control group
      attended weekly lectures. During months 6 to 12, each group received telephone
      contact only. Primary outcomes have been reported. Here we compare changes in
      exploratory outcomes of mobility loss (the inability to climb a flight of stairs
      or walk one-quarter mile without assistance), walking velocity, and the Short
      Physical Performance Battery. Compared to controls, fewer participants randomized
      to the intervention experienced mobility loss at 6-month follow-up: 6.3% versus
      26.5%, P=0.002, odds ratio=0.19 (95% CI=0.06 to 0.58) and at 12-month follow-up:
      5.2% versus 18.5%, P=0.029, odds ratio=0.24 (95% CI=0.06 to 0.97). The
      intervention improved fast-paced 4-m walking velocity at 6-month follow-up
      (P=0.005) and the Short Physical Performance Battery at 12-month follow-up
      (P=0.027), compared to controls. CONCLUSIONS: In exploratory analyses, a group
      mediated cognitive behavioral intervention promoting unsupervised walking
      exercise prevented mobility loss and improved functioning at 6- and 12-month
      follow-up in PAD patients. CLINICAL TRIAL REGISTRATION: URL:
      http://clinicaltrials.gov. Unique identifier: NCT00693940.

PMID- 25994446
TI  - Race and ethnicity, obesity, metabolic health, and risk of cardiovascular disease
      in postmenopausal women.
AB  - BACKGROUND: It is unclear whether obesity unaccompanied by metabolic
      abnormalities is associated with increased cardiovascular disease risk across
      racial and ethnic subgroups. METHODS AND RESULTS: We identified 14 364
      postmenopausal women from the Women's Health Initiative who had data on fasting
      serum lipids and serum glucose and no history of cardiovascular disease or
      diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as
      normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to
      <30), or obese (body mass index >=30) and by metabolic health, defined first as
      the metabolic syndrome (metabolically unhealthy: >=3 metabolic abnormalities) and
      second as the number of metabolic abnormalities. We used Cox proportional hazards
      regression to assess associations between baseline characteristics and
      cardiovascular risk. Over 13 years of follow-up, 1101 women had a first
      cardiovascular disease event (coronary heart disease or ischemic stroke). Among
      black women without metabolic syndrome, overweight women had higher adjusted
      cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas
      among white women without metabolic syndrome, overweight women had similar risk
      to normal weight women (HR 0.92, interaction P=0.05). Obese black women without
      metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR
      1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities,
      cardiovascular risk was increased in black women who were overweight (HR 1.77) or
      obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR
      1.06). Overweight and obese women with <=1 metabolic abnormality did not have
      increased cardiovascular risk, regardless of race or ethnicity. CONCLUSIONS:
      Metabolic abnormalities appeared to convey more cardiovascular risk among black
      women.

PMID- 25994447
TI  - Social support and its implications in older, early-stage breast cancer patients
      in CALGB 49907 (Alliance A171301).
AB  - BACKGROUND: Studies point to a direct association between social support and
      better cancer outcomes. This study examined whether baseline social support is
      associated with better survival and fewer chemotherapy-related adverse events in
      older, early-stage breast cancer patients. METHODS: This study is a pre-planned
      secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that
      compared standard adjuvant chemotherapy versus capecitabine in breast cancer
      patients 65 years of age or older. A subset reported on the extent of their
      social support with questionnaires that were completed 6 times over 2 years.
      RESULTS: The median age of this 331-patient cohort was 72 years (range: 65, 90);
      179 (55%) were married, and 210 (65%) lived with someone. One hundred forty-five
      patients (46%) described a social network of 0-10 people; 110 (35%) of 11-25; and
      58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey
      revealed that the median scores (range) for emotional/informational, tangible,
      positive social interaction, and affectionate social support were 94 (3, 100), 94
      (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores
      appeared stable over 2 years and higher (more support) than in other cancer
      settings. No statistically significant associations were observed between social
      support and survival and adverse events in multivariate analyses. However,
      married patients had smaller tumors, and those with arthritis reported less
      social support. CONCLUSION: Although social support did not predict survival and
      adverse events, the exploratory but plausible inverse associations with larger
      tumors and arthritis suggest that social support merits further study.

PMID- 25994448
TI  - Analysis of the acute systemic and tissue inflammatory response following carotid
      endarterectomy.
AB  - BACKGROUND: We aimed to investigate the acute systemic and tissue inflammatory
      response associated with carotid endarterectomy (CEA) and analyze the association
      between serum and tissue biomarkers and histological features of carotid plaques
      between symptomatic and asymptomatic patients. METHODS: We studied 11 patients (6
      symptomatic and 5 asymptomatic) with >=70% internal carotid stenosis treated with
      CEA. Serum expression of interleukin (IL) 1beta, IL-4, IL-6, IL-8, IL-10,
      metalloproteinase (MMP) 8, MMP-9, tumor necrosis factor-alpha (TNF-alpha), high
      sensitive C-reactive protein (hs-CRP), and vascular endothelial growth factor
      (VEGF) were measured in the preoperative period and 1, 6 and 24 hours after CEA.
      Assessment of tissue biomarkers (IL-1beta, IL-4, IL-6, IL-8, IL-10, MMP-8, MMP-9,
      TNF-alpha, and VEGF) and histological analyses were performed on carotid plaques.
      RESULTS: Peak serum values for MMP-8, MMP-9, IL-6, and IL 10 were observed 6
      hours after CEA, whereas for hs-CRP, TNF-alpha, and VEGF, they were identified 24
      hours after the procedure. Symptomatic patients exhibited higher serum
      concentrations of MMP-8, MMP-9, IL-1beta, IL-4, IL-8, hs-CRP and TNF-alpha and
      higher tissue concentrations of MMP-8, MMP-9, IL-1beta, IL-6 and VEGF than
      asymptomatic patients. Significant difference was found between symptomatic and
      asymptomatic patients in tissue IL-6 levels (30.95 pg/mL and 9.33 pg/mL,
      respectively; P=0.028). CONCLUSIONS: Systemic and tissue inflammatory response
      occurs even after CEA, being observed important activity of inflammatory and anti
      inflammatory cytokines at 6 and 24 hours after CEA. Symptomatic patients show
      higher concentrations of serum and tissue biomarkers in comparison to
      asymptomatic patients.

PMID- 25994449
TI  - Vascular anomalies of the large bowel.
AB  - INTRODUCTION: Vascular anomalies of the large bowel, commonly referred to as
      vascular malformations of the colon (VMC) constitute a rare but important
      condition, potentially causing significant morbidity and mortality. Our aim is to
      provide an up-to-date, practical summary evaluating this disease entity,
      focussing on pathogenesis, as well as diagnostic and therapeutic modalities.
      MATERIALS AND METHODS: We reviewed available data in the literature, and
      discussed it in the form of a narrative, readily applicable review. RESULTS: Most
      VMC (over 70%) are detected in the caecum and ascending colon, and affect people
      aged over 50 years. VMC are almost always symptomatic, presenting with lower
      bleeding. Endoscopy is crucial to identify and locate VMC, and to treat the
      lesions. In patients who fail or do not fit endoscopic treatment, aggressive
      approaches (interventional angiology or surgery) are mandatory. Up to 40% of
      patients may have relapse in the long term. CONCLUSIONS: VMC are rare but
      potentially life-threatening. Advances in endoscopic imaging and therapy have
      improved the results of treatment. Long-term follow-up after treatment is
      recommended.

PMID- 25994450
TI  - Can standard endovascular abdominal aortic aneurysm repair be performed as a day
      case in selected patients?

PMID- 25994451
TI  - Novel oral anticoagulants in the treatment of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely
      diverse clinical features, predisposing factors, brain imaging findings, and
      outcome. Anticoagulation is the cornerstone of CVT management, however, it is not
      supported by high-quality evicence. Novel oral anticoagulants (NOACs) have been
      extensively studied in patients with deep vein thrombosis, pulmonary embolism and
      non-valvular atrial fibrillation. The aim of our work was to review the available
      evidence for NOACs in the treatment of CVT. Based on our literature search there
      is insufficient evidence to support the use of NOACs in CVT, although case series
      with rivaroxaban and dabigatran have showed promising results. 

PMID- 25994452
TI  - In response to systematic review and meta-analysis of Meniett therapy for
      Meniere's disease.

PMID- 25994453
TI  - Hepatitis E virus co-infection in HIV-infected patients in Foggia and Naples in
      southern Italy.
AB  - BACKGROUND: Hepatitis E virus (HEV) infection represents an emerging infection in
      developed countries and is thought to be a zoonotic infection. It has recently
      been described as a new causative agent of acute and chronic hepatitis in
      immunosuppressed subjects, including HIV-infected patients. The aim of this study
      was to assess the sero-virological prevalence of HEV in HIV patients and in the
      general population as control group. METHODS: A prospective and observational
      cohort study was carried out in two hospitals in southern Italy. The
      seroprevalence of HEV was determined in a cohort of 959 subjects, 509 (53%) of
      whom were HIV-positive patients and 450 were from the general population. Serum
      samples were tested for anti-HEV antibodies; repeatedly positive results were
      confirmed by a Western blot assay. In positive patients HEV RNA and genotypes
      were also determined. RESULTS: A total of 46 (4.8%) of the 959 serum samples
      examined were reactive to anti-HEV Ig and confirmed by Western blotting. The
      prevalence of HEV antibodies (IgG and/or IgM) was 2.7% in the control group and
      6.7% in HIV-infected patients. Anti-HEV IgM was found in 6/46 (13.0%) of the anti
      HEV Ig-positive serum samples, in 5/34 HIV patients and in 1/12 of the general
      population. No HIV-infected patient presented chronic hepatitis with HEV
      infection alone. CONCLUSIONS: This study indicates a higher circulation of HEV in
      HIV-infected patients, whereas a low prevalence of HEV antibodies in the general
      Italian population was shown. Chronic hepatitis with HEV alone was absent, while
      it was present in subjects with HIV-HEV, co-infected with hepatitis B virus (HBV)
      and/or hepatitis C virus (HCV).

PMID- 25994454
TI  - Tickets to Glyndebourne or the Oval? Big tobacco's bid to woo parliamentarians.

PMID- 25994455
TI  - Opening of triangular hole in triangular-shaped chemical vapor deposited
      hexagonal boron nitride crystal.
AB  - In-plane heterostructure of monolayer hexagonal boron nitride (h-BN) and graphene
      is of great interest for its tunable bandgap and other unique properties. Here,
      we reveal a H2-induced etching process to introduce triangular hole in triangular
      shaped chemical vapor deposited individual h-BN crystal. In this study, we
      synthesized regular triangular-shaped h-BN crystals with the sizes around 2-10
      MUm on Cu foil by chemical vapor deposition (CVD). The etching behavior of
      individual h-BN crystal was investigated by annealing at different temperature in
      an H2:Ar atmosphere. Annealing at 900  degrees C, etching of h-BN was observed
      from crystal edges with no visible etching at the center of individual crystals.
      While, annealing at a temperature >= 950  degrees C, highly anisotropic etching
      was observed, where the etched areas were equilateral triangle-shaped with same
      orientation as that of original h-BN crystal. The etching process and well
      defined triangular hole formation can be significant platform to fabricate planar
      heterostructure with graphene or other two-dimensional (2D) materials.

PMID- 25994456
TI  - Clinical validity of consultant technical skills assessment in the English
      National Training Programme for Laparoscopic Colorectal Surgery.
AB  - BACKGROUND: The English National Training Programme for Laparoscopic Colorectal
      Surgery introduced a validated objective competency assessment tool to accredit
      surgeons before independent practice. The aim of this study was to determine
      whether this technical skills assessment predicted clinical outcomes. METHODS:
      Established consultants, training in laparoscopic colorectal surgery, were asked
      to submit two operative videos for evaluation by two blinded assessors using the
      competency assessment tool. A mark of 2.7 or above was considered a pass.
      Clinical and oncological outcomes were compared above and below this mark,
      including regression analysis. RESULTS: Eighty-five consultant surgeons submitted
      171 videos. Of these, 44 (25.7 per cent) were in the fail group (score less than
      2.7). This low scoring group had more postoperative morbidity (25 versus 8.7 per
      cent; P = 0.005), including surgical complications (18 versus 6.3 per cent; P =
      0.020) and fewer lymph nodes harvested (median 13 versus 18; P = 0.004). A score
      of less than 2.7 was an independent predictor of surgical complication, lymph
      node yield and distal resection margin clearance. Consultants with higher scores
      had performed similar numbers of laparoscopic colorectal operations (median 37
      versus 40; P = 0.373) but more structured training operations (18 versus 9; P <
      0.001). CONCLUSION: An objective technical skills assessment provided a
      discriminatory tool with which to accredit laparoscopic colorectal surgeons.

PMID- 25994457
TI  - Benchmark studies of UV-vis spectra simulation for cinnamates with UV filter
      profile.
AB  - Skin cancer is a serious public health problem worldwide, being incident over all
      five continents and affecting an increasing number of people. As sunscreens are
      considered an important preventive measure, studies to develop better and safer
      sunscreens are crucial. Cinnamates are UVB filters with good efficiency and cost
      benefit, therefore, their study could lead to the development of new UV filters.
      A benchmark to define the most suitable density functional theory (DFT)
      functional to predict UV-vis spectra for ethylhexyl methoxycinnamate was
      performed. Time-dependent DFT (TD-DFT) calculations were then carried out
      [B3LYP/6-311 + G(d,p) and B3P86/6-311 + G(d,p) in methanol environment] for seven
      cinammete derivatives implemented in the Gaussian 03 package. All DFT/TD-DFT
      simulations were performed after a conformational search with the Monte-Carlo
      method and MMFF94 force field. B3LYP and B3P86 functionals were better at
      reproducing closely the experimental spectra of ethylhexyl methoxycinnamate.
      Calculations of seven cinnamates showed a lambdamax of around 310 nm,
      corroborating literature reports. It was observed that the energy for the main
      electronic transition was around 3.95 eV and could be explained by electron
      delocalization on the aromatic ring and ester group, which is important to UV
      absorption. The methodology employed proved to be suitable for determination of
      the UV spectra of cinnamates and could be used as a tool for the development of
      novel UV filters. 

PMID- 25994458
TI  - Comparative modeling of hypothetical amyloid pores based on cylindrin.
AB  - Cylindrin is a six-stranded antiparallel beta barrel obtained from amyloidogenic
      strands of crystallin. It induces cell toxicity through an unknown mechanism. In
      this work, the potential use of the structure of cylindrin as a template for
      modeling amyloid pores-hypothetical transmembrane structures which appear during
      amyloid diseases-was studied. Using comparative modeling (performed by Modeller),
      we tested the stability of cylindrin-based pores made from several amyloid
      forming and non-amyloid-forming strands deriving from mutated cylindrin and the
      prion sup35. We showed that cylindrin could be used as a template for modeling
      pores made from strands of amyloid proteins, but that the cylindrin structure
      does not result from the amyloidogenicity of these fragments, as fibril non
      formers from the prion were also able to form a similar structure. Finally, we
      tested whether the cellular toxicity of cylindrin and related structures could be
      due to its incorporation into the cell membrane, leading to the creation of
      conducting ionic channels. The results of modeling indicate that cylindrin and
      tandem-repeat cylindrin, mutants of them, and cylindrin-like amyloid pores from
      prion sequences can only localize on the periphery of the membrane, and are not
      able to conduct any ions into the cell. These findings explain experimental
      results obtained for large unilamellar vesicles incubated with cylindrin, where
      conductance was not observed. 

PMID- 25994459
TI  - [The POISE-2 Aspirin trial].

PMID- 25994460
TI  - [The POISE-2 Clonidine trial].

PMID- 25994461
TI  - [The 2014 American and European guidelines on cardiovascular evaluation before
      noncardiac surgery: "less is probably more"].

PMID- 25994462
TI  - [Non-cardiac surgery in patients with previous percutaneous coronary intervention
      according to the 2014 European guidelines].

PMID- 25994463
TI  - [The surprising (?) results of IMPROVE-IT].

PMID- 25994464
TI  - [Who should implement cardiovascular prevention and health promotion?].

PMID- 25994465
TI  - [Mutations of APOC3 gene, metabolism of triglycerides and reduction of ischemic
      cardiovascular events].
AB  - A direct relationship between high plasma triglyceride (TG) levels and increased
      risk of cardiovascular disease has been shown in several studies. TG are present
      in the blood associated with different lipoprotein classes, including hepatically
      derived very low density lipoproteins (VLDL) and intestinally-derived
      chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG,
      releasing free fatty acids that accumulate in peripheral tissues and remnant
      lipoproteins, that are then cleared by the liver. LPL activity is finely
      modulated by several cofactors, including apolipoprotein C-III (apoC-III) which
      acts as a LPL inhibitor. The key role of apoCIII has been established in several
      studies: animal models lacking APOC3 gene exhibit reduced plasma TG levels,
      whereas the overexpression of APOC3 gene led to increased TG levels. In humans,
      several mutations in APOC3 gene have been identified, leading to lower apoC-III
      levels and associated with reduced plasma TG levels. Recently, these mutations
      were found to be associated with a reduced risk for cardiovascular ischemia and
      coronary heart disease, thus confirming the negative role of apoC-III in TG
      metabolism and suggesting apoC-III as possible therapeutic target for the
      management of hypertriglyceridemia. 

PMID- 25994466
TI  - [Remote monitoring of implantable cardiac devices: health technology assessment
      ].
AB  - Clinical follow-up of patients with cardiac implantable electronic devices is
      challenging because of the increasing technical complexity of devices and
      clinical complexity of patients. Remote monitoring (RM) offers the opportunity to
      optimize clinic workflow and to improve device monitoring and patient management
      by reducing in-hospital visits, physician and nurse time required for patient
      follow-up, and hospital and social costs. Continuous RM may lead to early
      detection of device malfunctions and clinical events, such as arrhythmias and
      heart failure. Early reaction may improve patient outcome. RM is easy to use and
      patients show a high level of acceptance and satisfaction. Implementing RM in
      daily practice may require changes in clinical workflow. Primary nursing-based
      models have demonstrated the best results. In spite of a favorable cost-benefit
      ratio, RM reimbursement still represents an issue in several European countries,
      including Italy, which limits widespread RM utilization. The fee-for-service
      payment approach, the global budget for device patient follow-up and/or
      integrated care packages for heart failure management represent the keys to
      introduce reimbursement and to improve patient care, while reducing healthcare
      costs. 

PMID- 25994467
TI  - [The heart of Italians. A population survey on the perception and evaluation of
      the National Health Service by citizens with heart disease and without heart
      disease (with special reference to cardiology)].
AB  - BACKGROUND: The purpose of this study was to collect information to understand
      how citizens perceive the National Health System (NHS), and what is the degree of
      confidence they have in the NHS. METHODS: We carried out an opinion poll with the
      Demos & Pi group on the perception of the NHS by Italian citizens, with
      particular reference to the activities related to cardiology, by interviewing
      2311 people with a set of 33 questions, about the perception of their health
      status, lifestyles, the propensity to use public or private services,
      consideration of the level of the NHS, and the trust in the medical profession.
      The subjects included were also preliminarily stratified according to the
      presence or absence of heart disease. RESULTS: Overall, Italian citizens express
      a high level of satisfaction for the NHS (on average, 65% of approval rating),
      including the whole professional staff, hoping that the NHS will be kept
      appropriately funded. The result is even better in the subset of interviewed
      citizens, who suffered from cardiovascular disease. People also consider the NHS
      an essential requirement to ensure equity in access to medical treatment and to
      keep costs competitive, even compared to private healthcare. The NHS major
      weakness remains the waiting lists, which are considered too long for diagnostic
      procedures and ordinary interventions. CONCLUSIONS: There is a widespread
      positive feeling among Italian citizens concerning the role and functioning of
      the NHS. Such opinion, shared by the whole country, should be taken into account
      when the time will come to define strategies for health policy of the Italian
      society in the near future.

PMID- 25994469
TI  - [Acute coronary syndrome and cancer: which therapeutic option first?].
AB  - Cardiovascular disease and cancer are the leading causes of mortality worldwide.
      We report our experience in a cancer patient with acute coronary syndrome
      successfully treated by hybrid revascularization, i.e. off-pump coronary artery
      bypass grafting, followed by surgical removal of the tumor and percutaneous
      coronary intervention. The concomitant presence of cancer and acute coronary
      syndrome is not rare, ranging from 1.9% to 4.2%. Usually, the most life
      threatening disease should be treated first, more frequently coronary artery
      disease. There are several therapeutic approaches to patients with cancer and
      coronary artery disease and cancer, including percutaneous coronary intervention,
      surgical treatment of cancer, or coronary artery bypass grafting. Each of these
      options should consider the severity of cardiac disease, the stage of malignancy
      and the clinical conditions of the patient. 

PMID- 25994468
TI  - [A simple but very complicated angioplasty: management of coronary artery
      perforation and dual antiplatelet therapy. A case report and literature review].
AB  - Coronary artery perforation is a rare but potentially fatal complication.
      Therefore, it is crucial for interventional cardiologists to have knowledge of
      this condition and what management strategies are available, particularly in the
      case of procedures with a high level of complexity. Notwithstanding this, even
      simple procedures are not immune to serious complications, as described in this
      case report where coronary angioplasty was complicated by left anterior
      descending artery perforation with cardiac tamponade, giving rise to multiple
      complications of difficult management. The case presented here also provides the
      opportunity to investigate the optimal duration of dual antiplatelet therapy
      after implantation of drug-eluting stents, a topic much debated in recent years. 

PMID- 25994470
TI  - [Pulmonary autograft dysfunction mimicking severe aortic stenosis].

PMID- 25994471
TI  - [The heart of Nicholas Green - why the transplant matters].

PMID- 25994472
TI  - [The heart of Nicholas Green - why transplant matters].

PMID- 25994475
TI  - A flow-free droplet-based device for high throughput polymorphic crystallization.
AB  - Crystallization is one of the most crucial steps in the process of pharmaceutical
      formulation. In recent years, emulsion-based platforms have been developed and
      broadly adopted to generate high quality products. However, these conventional
      approaches such as stirring are still limited in several aspects, e.g., unstable
      crystallization conditions and broad size distribution; besides, only simple
      crystal forms can be produced. In this paper, we present a new flow-free droplet
      based formation process for producing highly controlled crystallization with two
      examples: (1) NaCl crystallization reveals the ability to package saturated
      solution into nanoliter droplets, and (2) glycine crystallization demonstrates
      the ability to produce polymorphic crystallization forms by controlling the
      droplet size and temperature. In our process, the saturated solution
      automatically fills the microwell array powered by degassed bulk PDMS. A critical
      oil covering step is then introduced to isolate the saturated solution and
      control the water dissolution rate. Utilizing surface tension, the solution is
      uniformly packaged in the form of thousands of isolating droplets at the bottom
      of each microwell of 50-300 MUm diameter. After water dissolution, individual
      crystal structures are automatically formed inside the microwell array. This
      approach facilitates the study of different glycine growth processes: alpha-form
      generated inside the droplets and gamma-form generated at the edge of the
      droplets. With precise temperature control over nanoliter-sized droplets, the
      growth of ellipsoidal crystalline agglomerates of glycine was achieved for the
      first time. Optical and SEM images illustrate that the ellipsoidal agglomerates
      consist of 2-5 MUm glycine clusters with inner spiral structures of ~35 MUm screw
      pitch. Lastly, the size distribution of spherical crystalline agglomerates (SAs)
      produced from microwells of different sizes was measured to have a coefficient
      variation (CV) of less than 5%, showing crystal sizes can be precisely controlled
      by microwell sizes with high uniformity. This new method can be used to reliably
      fabricate monodispersed crystals for pharmaceutical applications. 

PMID- 25994474
TI  - Abnormal rate of intraoperative and postoperative implant positioning outliers
      using "MRI-based patient-specific" compared to "computer assisted"
      instrumentation in total knee replacement.
AB  - PURPOSE: The aim of this study was to analyze first intraoperative alignment and
      reason to abandon the use of patient-specific instrumentation using
      intraoperative CAS measurement, secondly assess by postoperative CT analysis if
      CI, based on preoperative 3D-MRI data, improved postoperative component
      positioning (including femoral rotation) and lower limb alignment as compared
      with results obtained with CAS. METHODS: In this randomized controlled trial, 80
      consecutive patients scheduled to undergo TKA were enrolled. Eligible knees were
      randomized to the group of PSI-TKAs (n = 40) or to the group of CAS-TKAs (n =
      40). In the CAS group, CAS determined and controlled cutting block positioning in
      each plane. In the PSI group, CAS allowed to measure adequacy of intraoperative
      alignment including femoral component rotation. At 3 months after surgery,
      implants position were measured and analyzed with full-weight bearing plain
      radiographs and CT scan. RESULTS: Intraoperatively, there was a significant
      difference concerning Sagittal Femoral mechanical, Frontal tibial mechanical
      angle and tibial slope between the two groups (respectively p = 0.01, p = 0.02, p
      = 0.046). Custom instrumentation was abandoned intraoperatively in seven knees
      (17.5 %). Abnormal tibial cuts were responsible of the abandon in three out of
      seven cases, femoral cut in 1/7 and dual abnormalities in 3/7. Postoperatively,
      tibial slope outliers percentage was higher in the patient specific
      instrumentation group with six patients (18.18 %) versus one patient (2.5 %) in
      the CAS group (p = 0.041). CONCLUSION: Patient specific instrumentation was
      associated with an important number of hazardous cut and a higher rate of
      outliers in our series and thus should be used with caution as related to. This
      study is the first to our acknowledgement to compare intra-operative ancillary
      and implant positioning of PSI-TKA and CAS-TKA. High rate of malposition are
      sustained by our findings, as such PSI-TKA should be used with caution, by
      surgeons capable to switch to conventional instrumentation intra-operatively.
      LEVEL OF EVIDENCE: Randomized control trial, Level I.

PMID- 25994477
TI  - Isolated, invisible, and in-need: there should be no "I" in caregiver.

PMID- 25994478
TI  - The development and evaluation of a multimedia resource for family carers of
      patients receiving palliative care: a consumer-led project.
AB  - OBJECTIVE: Previous intervention research has shown that group education sessions
      for carers are effective but not always feasible due to the demands of the
      caregiving role and the difficulty in getting carers to attend. This project was
      a consumer-led research initiative to develop and evaluate a multimedia resource
      (DVD) providing information and support for carers of people receiving palliative
      care. METHOD: Eight carers were recruited from a community palliative care
      service to form a steering committee for the project. In collaboration with two
      researchers, the committee discussed the topics that would be included in the
      resource, developed an interview guide, participated in the filmed interviews,
      and developed the evaluation program. The steering committee participated in a
      focus group as part of the evaluation to elicit their experiences of the project.
      An evaluation was conducted that included the following: questionnaires for 29
      carers and 17 palliative care health professionals; follow-up telephone
      interviews with carers; a focus group with health professionals; and a focus
      group with the Carer Steering Committee. RESULTS: The carers and health
      professionals reported that the DVD was informative (93 and 94%, respectively),
      realistic (96 and 88%), supportive (93 and 88%), and helpful (83 and 100%). All
      health professionals and carers reported that they would recommend the resource
      to carers. Carers on the steering committee reported substantial benefits that
      involved the opportunity to help others and to openly discuss and reflect on
      their experiences. SIGNIFICANCE OF RESULTS: This is an important resource that
      can be utilized to support family carers and introduce palliative care.
      Currently, 1500 copies have been distributed to palliative care services and
      professionals nationwide and is available online at
      centreforpallcare.org/index.php/resources/carer_dvd/. Development of this DVD
      represents a strong collaboration between carers and researchers to produce a
      resource that is informative, supportive, and meaningful.

PMID- 25994479
TI  - Factors associated with feelings of reward during ongoing family palliative
      caregiving.
AB  - OBJECTIVE: Of the few studies that have paid attention to feelings of reward in
      family palliative caregiving, most are retrospective and examine the experiences
      of bereaved family caregivers. Although feeling rewarded has been described as an
      influence that may facilitate the way family caregivers handle the caregiving
      situation, no study has sought to identify the factors associated with feelings
      of reward while providing ongoing family palliative care. The aim of this study,
      therefore, was to identify influential factors in feelings of reward experienced
      by family palliative caregivers. METHOD: Our study had a correlational cross
      sectional design. Family caregivers (n = 125) of patients receiving specialized
      palliative care were consecutively recruited from four settings. These caregivers
      answered a questionnaire that included the Rewards of Caregiving Scale (RCS).
      This questionnaire included questions about demographic background and scales to
      measure preparedness for caregiving, feelings of hope, perceived health, and
      symptoms of anxiety and depression. Correlation and regression analyses were
      conducted to identify factors associated with rewards. RESULTS: The results
      demonstrated that the more prepared caregivers with higher levels of hope felt
      more rewarded, while caregivers with higher levels of anxiety and those in a
      spousal relationship with the patient felt less rewarded by caregiving.
      SIGNIFICANCE OF RESULTS: It seems reasonable that feeling rewarded can be a
      significant contributor to the overall experience of providing ongoing palliative
      care. The situation of family caregivers has been shown to be multifaceted and
      complex, and such covariant factors as preparedness, anxiety, hope, and being in
      a spousal relationship with the patient to influence this experience.

PMID- 25994480
TI  - Effect of a single and repeated stress exposure on gene expression of
      catecholamine biosynthetic enzymes in brainstem catecholaminergic cell groups in
      rats.
AB  - Brainstem catecholaminergic neurons significantly participate in the regulation
      of neuroendocrine system activity, particularly during stressful conditions.
      However, so far the precise quantitative characterisation of basal and stress
      induced changes in gene expression and protein levels of catecholaminergic
      biosynthetic enzymes in these neurons has been missing. Using a quantitative
      reverse transcription-polymerase chain reaction method, we investigated gene
      expression of catecholamine biosynthetic enzymes in brainstem noradrenergic and
      adrenergic cell groups in rats under resting conditions as well as in acutely and
      repeatedly stressed animals. For the first time, we described quantitative
      differences in basal levels of catecholamine biosynthetic enzyme mRNA in
      brainstem catecholaminergic ascending and descending projecting cell groups.
      Moreover, we found and defined some differences among catecholaminergic cell
      groups in the time-course of mRNA levels of catecholaminergic enzymes following a
      single and especially repeated immobilisation stress. The data obtained support
      the assumption that brainstem catecholaminergic cell groups represent a
      functionally differentiated system, which is highly (but specifically) activated
      in rats exposed to stress. Therefore, potential interventions for the treatment
      of stress-related diseases need to affect the activity of brainstem
      catecholaminergic neurons not uniformly but with some degree of selectivity. 

PMID- 25994481
TI  - A new look at the essence of the imaging photoplethysmography.
AB  - Photoplethysmography (PPG) is a noninvasive optical method accepted in the
      clinical use for measurements of arterial oxygen saturation. It is widely
      believed that the light intensity after interaction with the biological tissue in
      vivo is modulated at the heartbeat frequency mainly due to pulsatile variations
      of the light absorption caused by arterial blood-volume pulsations. Here we
      report experimental observations, which are not consistent with this model and
      demonstrate the importance of elastic deformations of the capillary bed in the
      formation of the PPG waveform. These results provide new insight on light
      interaction with live tissue. To explain the observations we propose a new model
      of PPG in which pulse oscillations of the arterial transmural pressure deform the
      connective-tissue components of the dermis resulting in periodical changes of
      both the light scattering and absorption. These local changes of the light
      interaction parameters are detected as variations of the light intensity returned
      to a photosensitive camera. Therefore, arterial pulsations can be indirectly
      monitored even by using the light, which slightly penetrates into the biological
      tissue. 

PMID- 25994482
TI  - Enhancement of skin permeation of flurbiprofen via its transdermal patches using
      isopulegol decanoate (ISO-C10) as an absorption enhancer: pharmacokinetic and
      pharmacodynamic evaluation.
AB  - OBJECTIVES: The study aimed to prepare a transdermal patch for flurbiprofen using
      isopulegol decanoate (ISO-C10) as a permeation enhancer, and to evaluate the in
      vitro and in-vivo percutaneous permeation of the drug, as well as the
      pharmacodynamic efficacy of the formulation. METHODS: The permeation experiments
      were conducted on rabbit skin, and the pharmacokinetic profiles and synovial
      fluid drug concentration were measured after in-vivo transdermal administration.
      A deconvolution approach was employed to analyse the correlation between the in
      vitro and in-vivo drug permeation. The anti-inflammatory and analgesic effects
      were, respectively, assessed using the adjuvant arthritis model and the acetic
      acid induced pain model. KEY FINDINGS: ISO-C10 could increase the in-vitro
      permeation of flurbiprofen from 46.22 +/- 5.65 MUg/cm(2) to 101.07 +/- 10.85
      MUg/cm(2) . The in-vivo absorption of the drug was also improved by the enhancer,
      and a good linear correlation was observed between the in-vitro and in-vivo drug
      permeation. Meanwhile, the ISO-C10 contained patches increased the drug
      disposition in synovial fluid and enhanced the pharmacodynamic efficacy of the
      formulation. CONCLUSIONS: ISO-C10 would be a promising permeation enhancer for
      improving the in-vitro and in-vivo delivery of flurbiprofen from its transdermal
      patches.

PMID- 25994483
TI  - Deteriorated and unchanged patients in psychological treatment in Swedish primary
      care and psychiatry.
AB  - BACKGROUND: Despite substantial effect sizes for psychological therapy among
      different diagnosis groups and in different treatment contexts, many studies show
      that a large proportion of patients do not attain reliable improvement and a
      substantial portion are worse off after treatment. Previous studies suggest that
      patients in psychiatry may have worse outcome than patients in primary care.
      AIMS: In this practice-based study of psychological treatment in Swedish primary
      care and adult psychiatry, the proportions of patients who did not improve and
      who deteriorated were assessed. METHODS: Proportions of reliably improved,
      unchanged, and reliably deteriorated patients among 840 patients in primary care
      and 317 patients in specialist psychiatry were assessed by self-ratings using the
      Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM). RESULTS:
      More than half of the patients did not change reliably. About 2% of the patients
      in primary care and 7% in psychiatry deteriorated. Multilevel analyses of the
      data from primary care indicated that there were no therapist effects.
      CONCLUSIONS: The results emphasize the importance of monitoring treatment
      continuously in order to increase results for patients who do not improve.

PMID- 25994484
TI  - The Phosphatase-Resistant Isoform of CaMKI, Ca2+/Calmodulin-Dependent Protein
      Kinase Idelta (CaMKIdelta), Remains in Its "Primed" Form without Ca2+
      Stimulation.
AB  - Ca2+/calmodulin-dependent protein kinase I (CaMKI) is known to play pivotal roles
      in Ca2+ signaling pathways. Four isoforms of CaMKI (alpha, beta, gamma, and
      delta) have been reported so far. CaMKI is activated through phosphorylation by
      the upstream kinase, CaMK kinase (CaMKK), and phosphorylates downstream targets.
      When CaMKI was transiently expressed in 293T cells, CaMKIalpha was not
      phosphorylated at all under low-Ca2+ conditions in the cells. In contrast, we
      found that CaMKIdelta was significantly phosphorylated and activated to
      phosphorylate cAMP response element-binding protein (CREB) under the same
      conditions. Herein, we report that the sustained activation of CaMKIdelta is
      ascribed to its phosphatase resistance resulting from the structure of its N
      terminal region. First, we examined whether CaMKIdelta is more readily
      phosphorylated by CaMKK than CaMKIalpha, but no significant difference was
      observed. Next, to compare the phosphatase resistance between CaMKIalpha and
      CaMKIdelta, we assessed the dephosphorylation of the phosphorylated CaMKIs by
      CaMK phosphatase (CaMKP/PPM1F). Surprisingly, CaMKIdelta was hardly
      dephosphorylated by CaMKP, whereas CaMKIalpha was significantly dephosphorylated
      under the same conditions. To date, there have been no detailed reports
      concerning dephosphorylation of CaMKI. Through extensive analysis of CaMKP
      catalyzed dephosphorylation of various chimeric and point mutants of CaMKIdelta
      and CaMKIalpha, we identified the amino acid residues responsible for the
      phosphatase resistance of CaMKIdelta (Pro-57, Lys-62, Ser-66, Ile-68, and Arg
      76). These results also indicate that the phosphatase resistance of CaMKI is
      largely affected by only several amino acids in its N-terminal region. The
      phosphatase-resistant CaMKI isoform may play a physiological role under low-Ca2+
      conditions in the cells.

PMID- 25994485
TI  - New peptide architectures through C-H activation stapling between tryptophan
      phenylalanine/tyrosine residues.
AB  - Natural peptides show high degrees of specificity in their biological action.
      However, their therapeutical profile is severely limited by their conformational
      freedom and metabolic instability. Stapled peptides constitute a solution to
      these problems and access to these structures lies on a limited number of
      reactions involving the use of non-natural amino acids. Here, we describe a
      synthetic strategy for the preparation of unique constrained peptides featuring a
      covalent bond between tryptophan and phenylalanine or tyrosine residues. The
      preparation of such peptides is achieved in solution and on solid phase directly
      from the corresponding sequences having an iodo-aryl amino acid through an
      intramolecular palladium-catalysed C-H activation process. Moreover, complex
      topologies arise from the internal stapling of cyclopeptides and double
      intramolecular arylations within a linear peptide. Finally, as a proof of
      principle, we report the application to this new stapling method to relevant
      biologically active compounds. 

PMID- 25994486
TI  - Tooth brushing inhibits oral bacteria in dogs.
AB  - In this study, scaling, polishing and daily tooth brushing were performed in 20
      beagle dogs, and the number of oral bacteria was determined using a bacterial
      counter. The dogs were randomized into the scaling (S), scaling + polishing (SP),
      scaling + tooth daily brushing (SB) and scaling + polishing + tooth daily
      brushing (SPB) groups. Samples were collected from the buccal surface of the
      maxillary fourth premolars of the dogs immediately after scaling and every week
      thereafter from weeks 1 to 8. Throughout the study, the number of bacteria was
      significantly lower in the SB and SPB groups compared with the S group. The
      findings suggest that daily tooth brushing inhibited oral bacterial growth in the
      dogs. 

PMID- 25994487
TI  - Decaying toxic wood as sodium supplement for herbivorous mammals in Gabon.
AB  - African rainforest harbors herbivores at high density. However, because plants
      and soils typically lack in some essential minerals, rainforest is not always a
      suitable habitat for herbivores. How they fulfill the mineral requirements is
      therefore an important question to animal ecology and conservation. Although
      large marshes, called 'bais', are often mentioned as efficient mineral-resource,
      little information on other sodium resources has still been available. Our
      laboratory works and field surveys found that a peculiar item, decaying wood
      stumps of Anthostema aubryanum, played as a major sodium resource for herbivores
      in Moukalaba-Doudou National Park, Gabon. When A. aubryanum is alive, the sodium
      content of its bark is low and its latex is toxic. Sodium is accumulated in
      decaying stumps (mean=1,343 mg/kg dry matter). Eight herbivores visited stumps to
      ingest the dead wood. Fecal sample analysis revealed that western lowland
      gorillas, a species most-frequently using the stumps, consumed large amount of
      the dead wood as regular food. Our findings suggest that decaying A. aubryanum is
      critical sodium-resources and is a key species for herbivores in our study area.
      Importance of the A. aubryanum may be particularly large there, because it is a
      limited sodium-rich material that is available year round. Our study site is
      known as the site where the densities of several herbivores are among the highest
      at Central Africa. The relatively high herbivores density in our study site may
      partly depend on decaying A. aubryanum as sodium resources. 

PMID- 25994488
TI  - I Really Believe I Suffer From a Health Problem: Examining an Association Between
      Cognitive Fusion and Healthy Anxiety.
AB  - OBJECTIVE: This 2-part study provided the first known examination of an
      association between cognitive fusion and health anxiety. METHOD: This association
      was examined using 2 samples of community adults recruited through the Internet
      (Study 1: N = 252, mean [M] age = 31.2 years, 65.5% male; Study 2: N = 371,
      M(age) = 33.1 years, 56.9% male). RESULTS: In Study 1, cognitive fusion shared a
      moderate association with health anxiety that was not attributable to negative
      affect. Along with replicating Study 1 findings using an alternative measure of
      health anxiety, the association between cognitive fusion and health anxiety was
      found to be independent of experiential avoidance and anxiety sensitivity in
      Study 2. Cognitive fusion was most relevant to the affective and cognitive
      dimensions of health anxiety. CONCLUSION: The present findings are consistent
      with the possibility that cognitive fusion contributes to health anxiety. Future
      multivariate experimental and longitudinal studies are required to establish
      causality.

PMID- 25994489
TI  - Evaluation of individual sensitivity of head and neck squamous cell carcinoma to
      cetuximab by short-term culture of tumor slices.
AB  - BACKGROUND: Cetuximab is a targeted therapy with demonstrated efficacy in the
      management of head and neck squamous cell carcinoma (HNSCC). However, no
      laboratory assay is available to predict its efficacy in an individual patient.
      METHODS: Short-term cultures of tumor slices were performed on 9 tumor samples
      obtained after surgical resection in patients. Cancer cell proliferation was
      evaluated by immunohistochemistry and the impact of cetuximab on cell
      proliferation was examined. RESULTS: Tumor architecture and the heterogeneous
      composition of HNSCC were preserved for at least 48 hours during short-term
      culture of tumor slices. HNSCC cells demonstrated a heterogeneous individual
      response to cetuximab. CONCLUSION: Short-term culture of tumor slices is a
      strategy to estimate the clinical activity of cetuximab in individual patients
      with HNSCC. Further studies are required to correlate the results obtained with
      the clinical response of individual patients to cetuximab. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E911-E915, 2016.

PMID- 25994491
TI  - Commentary on Mata and von Helversen: Foraging Theory as a Paradigm Shift for
      Cognitive Aging.
AB  - Mata and von Helversen's integrative review of adult age differences in search
      performance makes a good case that cognitive control may impact certain aspects
      of self-regulation of search. However, information foraging as a framework also
      offers an avenue to consider how adults of different ages adapt to age-related
      changes in cognition, such as in cognitive control. 

PMID- 25994490
TI  - The role of PPAR activation during the systemic response to brain injury.
AB  - BACKGROUND: Fenofibrate, a PPAR-alpha activator, has shown promising results as a
      neuroprotective therapy, with proposed anti-inflammatory and anti-oxidant
      effects. However, it displays poor blood-brain barrier permeability leading to
      some ambiguity over its mechanism of action. Experimentally induced brain injury
      has been shown to elicit a hepatic acute phase response that modulates leukocyte
      recruitment to the injured brain. Here, we sought to discover whether one effect
      of fenofibrate might include the suppression of the acute phase response (APR)
      following brain injury. METHODS: A 1-h intraluminal thread middle cerebral artery
      occlusion (MCAO) model followed by a 6-h reperfusion was performed in C57/BL6
      mice. Quantitative reverse transcriptase-polymerase chain reaction was then used
      to measure hepatic expression of chemokine (C-X-C motif) ligand 1 (CXCL1),
      chemokine ligand 10 (CXCL10) and serum amyloid A-1 (SAA-1), and
      immunohistochemical analysis was used to quantify brain and hepatic neutrophil
      infiltration following stroke. RESULTS: The MCAO and sham surgery induced the
      expression of all three acute phase reactants. A 14-day fenofibrate pre-treatment
      decreased reactant production, infarct volume, and neutrophil recruitment to the
      brain and liver, which is a hallmark of the APR. CONCLUSIONS: The data highlight
      a novel mechanism of action for fenofibrate and lend further evidence towards the
      promotion of its use as a prophylactic therapy in patients at risk of cerebral
      ischaemia. Further research is required to elucidate the mechanistic explanation
      underlying its actions.

PMID- 25994492
TI  - Adaptive considerations of temperature dependence of neuromuscular function in
      two species of summer- and winter-caught Crab (Carcinus maenas and Cancer
      pagurus).
AB  - The aim of this study was to determine seasonal differences in the temperature
      dependence of neuromuscular parameters of the dactylopodite walking leg closer
      muscle in two species of freshly caught summer and winter decapod crabs. The
      relatively stenothermal Cancer pagurus (Cp) and eurythermal Carcinus maenas (Cm)
      muscle resting potential (RP) hyperpolarised significantly with increasing
      experimental temperature. The muscle RP in Cm was seasonally dependent at acute
      temperatures above 20  degrees C whereas in Cp no seasonal effect was observed.
      The latent period of the muscle excitatory junction potential (EJP) following
      tonic motor nerve stimulation was significantly longer in winter-caught crabs in
      both species, although the effect was significantly more marked in Cp than Cm.
      Summer-caught Cp had larger excitatory junction potentials (EJPs) than did winter
      caught crabs, a seasonal effect not seen in Cm. In contrast, marked seasonal
      differences were found in the EJP decay time constant in Cm having significantly
      longer time constants in winter-caught crabs, where no seasonal difference was
      found in Cp. These results suggest that different seasonal effects of
      neuromuscular parameters between Cm and Cp may reflect different strategies of
      response to their different seasonal temperature environments. 

PMID- 25994493
TI  - Phosphate Kinetics During Weekly Cycle of Hemodialysis Sessions: Application of
      Mathematical Modeling.
AB  - Both hyperphosphatemia and hypophosphatemia are associated with increased
      morbidity and mortality among patients on dialysis. The control of serum
      phosphate concentration is a considerable clinical problem. Our study aimed to
      improve understanding of phosphate kinetics in patients on dialysis using
      mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2-2
      3 days were monitored in 25 patients. Phosphate concentration was measured every
      hour and 45 min after the end of dialysis in blood serum and every 30 min in
      dialysate during each session. Volume of fluid compartments and body composition
      were assessed by bioimpedance. The pseudo one-compartment model was applied to
      describe the profile of phosphate in blood serum during intra- and interdialytic
      periods of 1-week cycle of three hemodialysis sessions. Model parameters, such as
      phosphate internal clearance (KM ) and the rate of phosphate mobilization (RM ),
      were correlated with the reduction of serum phosphate concentration during
      dialysis (Cpost /Cpre ) and with equivalent continuous clearance (ECC) for
      phosphate. KM correlated negatively with predialysis serum phosphate
      concentration. There was significant positive correlation between RM and age.
      Postdialysis volume of phosphate central compartment was lower than, but
      correlated to, extracellular water volume. Parameters of the pseudo one
      compartment model, phosphate internal clearance, and the rate of phosphate inflow
      to the central compartment (the one accessible for dialysis) from other phosphate
      body reservoirs correlated with the indices of dialysis adequacy, such as
      reduction of serum phosphate and ECC. The pseudo one-compartment model can be
      successfully extended from a single hemodialysis to the standard weekly cycle of
      sessions and the model parameters strongly correlate with the adequacy parameters
      of dialytic removal of phosphate. 

PMID- 25994494
TI  - Two key genomic regions harbour QTLs for salinity tolerance in ICCV 2 * JG 11
      derived chickpea (Cicer arietinum L.) recombinant inbred lines.
AB  - BACKGROUND: Although chickpea (Cicer arietinum L.), an important food legume
      crop, is sensitive to salinity, considerable variation for salinity tolerance
      exists in the germplasm. To improve any existing cultivar, it is important to
      understand the genetic and physiological mechanisms underlying this tolerance.
      RESULTS: In the present study, 188 recombinant inbred lines (RILs) derived from
      the cross ICCV 2 * JG 11 were used to assess yield and related traits in a soil
      with 0 mM NaCl (control) and 80 mM NaCl (salinity) over two consecutive years.
      Salinity significantly (P < 0.05) affected almost all traits across years and
      yield reduction was in large part related to a reduction in seed number but also
      a reduction in above ground biomass. A genetic map was constructed using 56
      polymorphic markers (28 simple sequence repeats; SSRs and 28 single nucleotide
      polymorphisms; SNPs). The QTL analysis revealed two key genomic regions on CaLG05
      (28.6 cM) and on CaLG07 (19.4 cM), that harboured QTLs for six and five different
      salinity tolerance associated traits, respectively, and imparting either higher
      plant vigour (on CaLG05) or higher reproductive success (on CaLG07). Two major
      QTLs for yield in the salinity treatment (explaining 12 and 17% of the phenotypic
      variation) were identified within the two key genomic regions. Comparison with
      already published chickpea genetic maps showed that these regions conferred
      salinity tolerance across two other populations and the markers can be deployed
      for enhancing salinity tolerance in chickpea. Based on the gene ontology
      annotation, forty eight putative candidate genes responsive to salinity stress
      were found on CaLG05 (31 genes) and CaLG07 (17 genes) in a distance of 11.1 Mb
      and 8.2 Mb on chickpea reference genome. Most of the genes were known to be
      involved in achieving osmoregulation under stress conditions. CONCLUSION:
      Identification of putative candidate genes further strengthens the idea of using
      CaLG05 and CaLG07 genomic regions for marker assisted breeding (MAB). Further
      fine mapping of these key genomic regions may lead to novel gene identification
      for salinity stress tolerance in chickpea.

PMID- 25994495
TI  - Patterns of genetic variation and life history traits of Zeuxapta seriolae
      infesting Seriola lalandi across the coastal and oceanic areas in the
      southeastern Pacific Ocean: potential implications for aquaculture.
AB  - BACKGROUND: The monogenean, Zeuxapta seriolae, is a host-specific parasite that
      has an extensive geographical distribution on its host, Seriola lalandi, and is
      considered highly pathogenic in farmed fish. In recent years, developing cultures
      of S. lalandi in different coastal localities in Southeastern Pacific Ocean (SEP)
      have been affected by moderate and heavy infections of this parasite, attributed
      to contagion from wild to farmed fish. Here, we evaluated the pattern of genetic
      variations and biological traits of Z. seriolae in a spatial and temporal scale
      across its geographical distribution in SEP to determine its genetic status and
      biological traits, which could affect its transmission dynamics from wild to
      farmed fish. METHODS: Wild fish and their parasites were sampled from fisheries
      in the northern Chilean coast (NCC: 24 degrees S-30 degrees S) and Eastern
      islands (JFA: ca 33 degrees S; 80 degrees W) between 2012 and 2014. Fragments of
      816 bp of the cytochrome c oxidase subunit I (COI) gene was sequenced for 112
      individuals from NCC and 63 from JFA and compared using AMOVA. Prevalence and
      intensity of Z. seriolae were calculated for each area. The parasite body size,
      fecundity and size at sexual maturity were estimated for 177 parasites from NCC
      and 128 from JFA, and significant differences were evaluated using GLM. RESULTS:
      Geographical genetic structuring was detected for Z. seriolae across SEP, with a
      population in NCC and the other in JFA, both with the same high haplotype
      diversity. Neutrality tests and mismatch analyses indicated that both Z. seriolae
      populations are stable. Parasite biological traits such as fecundity, body size,
      and size at sexual maturity, and population parameters varied significantly
      between geographical areas. CONCLUSION: Two genetic groups of Z. seriolae were
      detected in wild fish across SEP. Because of the seasonal migration of wild host
      and temporal contact with farming, quantifying the genetic diversity and level of
      gene flow or isolation between parasite populations is useful for fish health
      management in farming. The smallest size of sexual maturity in parasites from NCC
      is predictive of shorter life cycles, and their high genetic diversity suggests
      high evolutionary potential and high transmission of this parasite to farmed
      hosts.

PMID- 25994496
TI  - Selection, management, and outcome of vitamin K antagonist-treated patients with
      atrial fibrillation not switched to novel oral anticoagulants. Results from the
      Dresden NOAC registry.
AB  - Atrial fibrillation (AF) patients treated with well-controlled vitamin K
      antagonists (VKAs) may benefit less from non-vitamin K antagonist oral
      anticoagulants (NOACs) because they are supposed to be at low risk of
      thromboembolic and bleeding complications. However, little is known about the
      selection, management, and outcome of such "stable" VKA patients in current
      practice. We assessed characteristics, VKA persistence and 12 months' outcome of
      AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC
      registry opened recruitment of patients continuing on VKA for sites that had been
      actively recruiting AF patients treated with NOACs in the prior 18 months.
      Patient characteristics were compared with those of NOAC patients from the same
      sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding
      risk profile compared with 706 patients selected for NOAC treatment. For VKA,
      international normalised ratio time-in-therapeutic range before enrolment was 71
      % and increased to 75 % during a mean follow-up of 15 months. Rates of
      stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years
      (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate
      of ISTH major bleeding was 4.15/100 patient-years (95 % CI 2.60-6.29) with a case
      fatality rate of 16.3 % (all-cause mortality at day 90 after major bleeding). In
      conclusion, in daily care, AF patients selected for VKA therapy are healthier
      than those treated with NOAC, demonstrate a high quality of anticoagulant control
      and very low stroke rates. However, despite adequate patient selection and INR
      control, the risk of major VKA bleeding is unacceptably high and bleeding outcome
      is poor. 

PMID- 25994497
TI  - Imaging patients with renal colic-consider ultrasound first.
AB  - Renal colic is a common disease in Europe and a common cause of visit to the
      Emergency Department. Clinical diagnosis is usually confirmed by imaging
      modalities. Unenhanced computed tomography (CT) is considered the best diagnostic
      test due to its excellent accuracy detecting ureteral stones. However, ultrasound
      (US) should be considered as the primary imaging technique. It is a reproducible,
      non-invasive and non-expensive imaging technique, achieving accurate diagnosis in
      most cases without the need for radiation. Diagnosis is based on the presence of
      ureteral stones, but indirect findings such as the asymmetry or absence of
      ureteric jet, an increase of the resistive index or a colour Doppler twinkling
      artefact may help to suggest the diagnosis when the stone is not identified. MAIN
      MESSAGES: * Renal colic diagnosis is usually confirmed by imaging modalities. *
      Imaging diagnosis of renal colic is based on the detection of ureteral stones. *
      CT is the most accurate imaging technique to identify ureteral stones. * US
      allows correct diagnosis in most cases without using radiation. * US should be
      used as the first imaging modality in patients with renal colic.

PMID- 25994498
TI  - Relationship and stage of dementia differences in caregiver perspectives on the
      meaning of activity.
AB  - Caregivers of persons living with dementia (PWD) taking cholinesterase
      inhibitors, who care 3 + h over three days/week, were interviewed. This study
      uses thematic content analysis to compare responses to the open-ended question "
      What do you believe getting involved in activities outside the home means for
      someone with dementia?" in spouse ( n = 613) and adult-children ( n = 260)
      caregivers, and across mild ( n = 314) and moderate-severe stages ( n = 280). For
      adult-children caregivers, activity participation promotes independence in their
      parents. Spouses describe activity in the context of their relationship with the
      PWD, and the experience is framed around their continued social roles as a
      couple. Mild-stage caregivers report the difficulty and negative outcomes (e.g.
      frustration, stigma) of engaging in activity, while moderate-severe caregivers
      discuss activity as preserving abilities in PWD and providing connection to
      cohort. This may indicate areas for improved activity provision and support for
      spouse (i.e. emotional) and adult-children (i.e. resources) caregivers across
      dementia stages.

PMID- 25994499
TI  - Sociodemographic Characteristics and Psychological Adjustment Among Transsexuals
      in Spain.
AB  - This study examined the sociodemographic characteristics and the psychological
      adjustment of transsexuals in Andalusia (Spain), and also analyzed the
      differences between female-to-male (FtM) and male-to-female (MtF) transsexuals.
      The sample included 197 transsexuals (101 MtF and 96 FtM) selected from those who
      visited the Transsexual and Gender Identity Unit at the Carlos Haya Hospital in
      Malaga between 2011 and 2012. Our analyses indicated that MtF transsexuals were
      more likely to have lower educational levels, live alone, have worked less
      frequently throughout their lifetime, and have engaged in prostitution. For FtM
      transsexuals, there were more frequent references to the mother's psychiatric
      history and more social avoidance and distress. Multivariate analysis showed that
      the number of personality dysfunctional traits and unemployment status were
      associated with depression in the entire sample. The following three conclusions
      can be made: there are significant differences between MtF and FtM transsexuals
      (mainly related to sociodemographic variables), depression was high in both
      groups, and a remarkable percentage of transsexuals have attempted suicide (22.8
      %) or have had suicidal thoughts (52.3 %).

PMID- 25994500
TI  - Aminocarbonylation of aryl tosylates to carboxamides.
AB  - The palladium - catalyzed aminocarbonylation of aryl tosylates with amines is
      reported. Suitable conditions were identified by high throughput reaction
      screening and then further optimized. The substrate scope of the reaction with
      respect to the aryl tosylate component and the amine component are reported.
      Competitive aminolysis of the aryl tosylates to afford the amine
      toluenesulfonamides and the phenol was not observed. 

PMID- 25994501
TI  - Phase separation induced shell thickness variations in electrospun hollow
      Bioglass 45S5 fiber mats for drug delivery applications.
AB  - In the present study, sub-micron sized hollow Bioglass 45S5 nanofibers are
      synthesised using an electrospinning technique with the assistance of polyvinyl
      pyrrolidone. The electrospinning process parameters are optimized to obtain
      reproducible nanofibers. The effects of solvent and polymer concentrations on the
      morphology and formation of fibers are studied. Ethanol and water are used to
      vary the concentration and it is observed that an increase in dilution by water
      decreases the shell thickness of the hollow fibers. The mechanism of the
      formation of the hollow fibers is attributed to phase separation, which occurs
      during physical cooling of the fibers. Fibers prepared from a solution diluted
      with an equal ratio of ethanol and water show a higher performance in drug
      loading and releasing kinetics due to their narrow and linear size distribution.
      These fibers are also highly suitable for bone tissue engineering applications
      due to their linear fibrous 3D structural mat architecture and they are suitable
      for large size scaling. 

PMID- 25994502
TI  - Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review
      and Pooled Analysis.
AB  - PURPOSE: Tumour budding is defined as the presence of isolated or small clusters
      of malignant cells at the invasive edge of the tumour. It is considered a
      negative prognostic factor in colorectal cancer (CRC) and is associated with a
      poor outcome and adverse pathological features. Here, we report a meta-analysis
      of the association of tumour budding and survival in stage II CRC patients.
      METHODS: PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that
      assessed the relationship between tumour budding and 5-year overall survival (OS)
      in stage II CRC patients. Published data were extracted and used to compute odds
      ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst
      patients with respect to the extent of tumour budding, using multivariate
      analysis. Data were pooled using the Mantel-Haenszel random effect model.
      RESULTS: We analysed 12 studies that included a total of 1652 patients. High
      grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 %
      confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5
      year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly
      noteworthy that the presence of high-grade budding was associated with an
      increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001).
      CONCLUSIONS: Tumour budding is associated with worse survival in stage II CRC, in
      particular in pT3N0M0 patients. It could therefore potentially be used when
      deciding whether to administer adjuvant chemotherapy in high-risk node negative
      CRC patients.

PMID- 25994503
TI  - Erratum to: Preliminary findings of arterial embolization with balloon-occluded
      and flow-dependent histoacryl glue embolization in a swine model.

PMID- 25994504
TI  - Hesperidin ameliorates trichloroethylene-induced nephrotoxicity by abrogation of
      oxidative stress and apoptosis in wistar rats.
AB  - Trichloroethylene (TCE), a nephrotoxicant is known to cause severe damage to the
      kidney. In this study, the nephroprotective potential of hesperidin was evaluated
      against TCE-induced nephrotoxicity in wistar rats. Oral administration of TCE
      (1000 mg/kg b.wt) for 15 days enhanced renal lipid peroxidation and reduced
      antioxidant enzymes armoury viz., reduced renal glutathione, glutathione
      peroxidase, glutathione reductase, glutathione-S-transferase, catalase and
      superoxide dismutase. It also enhanced the levels of blood urea nitrogen,
      creatinine and kidney injury molecule (KIM-1). Caspase-3 and bax expression were
      found to be elevated, while that of bcl-2 reduced suggesting that TCE induces
      apoptosis. However, pretreatment with hesperidin at a dose of 100 and 200 mg/kg
      b.wt for 15 days significantly decreased lipid peroxidation, increased the levels
      of antioxidant enzymes and reduced blood urea, creatinine and KIM-1 levels.
      Hesperidin also modulated the apoptotic pathways by altering the expressions of
      caspase-3, bax and bcl-2 to normal. Our results suggest that hesperidin can be
      used as a nephroprotective agent against TCE-induced nephrotoxicity.

PMID- 25994505
TI  - Apigenin promotes osteogenic differentiation of human mesenchymal stem cells
      through JNK and p38 MAPK pathways.
AB  - Apigenin is a plant-derived flavonoid and has been reported to prevent bone loss
      in ovariectomized mice, but the role of apigenin on osteogenic differentiation of
      human mesenchymal stem cells (hMSCs) has not been reported. In the present study,
      the effect of apigenin on osteogenic differentiation of hMSCs was explored. Our
      results showed that apigenin treatment significantly increased alkaline
      phosphatase (ALP) activity and mineralization in hMSCs. RT-PCR revealed that
      apigenin markedly up-regulated the mRNA expression of osteopontin (OPN) and the
      transcription factors runt-related transcription factor 2 (Runx2). The expression
      of Runx2 and osterix (OSX) proteins were also increased in hMSCs differentiating
      into osteoblasts after treatment with apigenin. Furthermore, we investigated the
      signaling pathways responsible for osteogenic differentiation of apigenin in
      hMSCs. We found that apigenin treatment significantly increased the levels of p
      JNK, p-p38 in hMSCs and addition of the inhibitors of JNK (SP600125) or p38 MAPK
      (SB203580) eliminated the stimulating effects of apigenin. In addition, addition
      of SP600125 or SB203580 also blocked apigenin-induced ALP activity, OPN, Runx2,
      and OSX expression and meanwhile inhibited bone nodule formation. Taken together,
      these findings suggest apigenin promotes the osteogenesis of hMSCs through
      activation of JNK and p38 MAPK signal pathways which leads to Runx2 and OSX
      expressions to induce the formation of bone nodule. 

PMID- 25994506
TI  - Pyrazinamide resistance in Mycobacterium tuberculosis fails to bite?
AB  - In contrast to most other antimycobacterial drugs where--particularly in
      multidrug-resistant (MDR) strains--a limited number of resistance mutations
      dominate, pyrazinamide (PZA) resistance associated mutations remain highly
      diverse with limited clustering. This apparent lack of evolutionary selection for
      successful PZA resistance mechanisms deserves attention. A clear understanding of
      the epidemiology of PZA resistance acquisition and spread would be expected to
      result in important insights into how PZA might be better exploited in treatment
      regimens to minimize the amplification of Mycobacterium tuberculosis (MTB) drug
      resistance. We propose that PZA resistance typically induces a fitness cost that
      impairs MTB transmission. This would explain the lack of extensive clustering for
      PZA-resistant mutants. Our hypothesis also leads to a series of testable
      predictions which we outline that could confirm or refute our ideas.

PMID- 25994507
TI  - Critical role of the SPAK protein kinase CCT domain in controlling blood
      pressure.
AB  - The STE20/SPS1-related proline/alanine-rich kinase (SPAK) controls blood pressure
      (BP) by phosphorylating and stimulating the Na-Cl (NCC) and Na-K-2Cl (NKCC2) co
      transporters, which regulate salt reabsorption in the kidney. SPAK possesses a
      conserved carboxy-terminal (CCT) domain, which recognises RFXV/I motifs present
      in its upstream activator [isoforms of the With-No-lysine (K) kinases (WNKs)] as
      well as its substrates (NCC and NKCC2). To define the physiological importance of
      the CCT domain, we generated knock-in mice in which the critical CCT domain
      Leu502 residue required for high affinity recognition of the RFXI/V motif was
      mutated to Alanine. The SPAK CCT domain defective knock-in animals are viable,
      and the Leu502Ala mutation abolished co-immunoprecipitation of SPAK with WNK1,
      NCC and NKCC2. The CCT domain defective animals displayed markedly reduced SPAK
      activity and phosphorylation of NCC and NKCC2 co-transporters at the residues
      phosphorylated by SPAK. This was also accompanied by a reduction in the
      expression of NCC and NKCC2 protein without changes in mRNA levels. The SPAK CCT
      domain knock-in mice showed typical features of Gitelman Syndrome with mild
      hypokalaemia, hypomagnesaemia, hypocalciuria and displayed salt wasting on
      switching to a low-Na diet. These observations establish that the CCT domain
      plays a crucial role in controlling SPAK activity and BP. Our results indicate
      that CCT domain inhibitors would be effective at reducing BP by lowering
      phosphorylation as well as expression of NCC and NKCC2. 

PMID- 25994508
TI  - CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain
      catalytic activity and triggers intraocular inflammation in a mouse model.
AB  - A single amino acid mutation near the active site of the CAPN5 protease was
      linked to the inherited blinding disorder, autosomal dominant neovascular
      inflammatory vitreoretinopathy (ADNIV, OMIM #193235). In homology modeling with
      other calpains, this R243L CAPN5 mutation was situated in a mobile loop that
      gates substrate access to the calcium-regulated active site. In in vitro activity
      assays, the mutation increased calpain protease activity and made it far more
      active at low concentrations of calcium. To test whether the disease allele could
      yield an animal model of ADNIV, we created transgenic mice expressing human (h)
      CAPN5(R243L) only in the retina. The resulting hCAPN5(R243L) transgenic mice
      developed a phenotype consistent with human uveitis and ADNIV, at the clinical,
      histological and molecular levels. The fundus of hCAPN5(R243L) mice showed
      enhanced autofluorescence (AF) and pigment changes indicative of reactive retinal
      pigment epithelial cells and photoreceptor degeneration. Electroretinography
      showed mutant mouse eyes had a selective loss of the b-wave indicating an inner
      retina signaling defect. Histological analysis of mutant mouse eyes showed
      protein extravasation from dilated vessels into the anterior chamber and
      vitreous, vitreous inflammation, vitreous and retinal fibrosis and retinal
      degeneration. Analysis of gene expression changes in the hCAPN5(R243L) mouse
      retina showed upregulation of several markers, including members of the Toll-like
      receptor pathway, chemokines and cytokines, indicative of both an innate and
      adaptive immune response. Since many forms of uveitis share phenotypic
      characteristics of ADNIV, this mouse offers a model with therapeutic testing
      utility for ADNIV and uveitis patients. 

PMID- 25994510
TI  - Simultaneous Enantioseparation of Aldohexoses and Aldopentoses Derivatized With L
      Tryptophanamide by Reversed Phase HPLC Using Butylboronic Acid as a Complexation
      Reagent of Monosaccharides.
AB  - Three aldohexoses, glucose, galactose, and mannose, and three aldopentoses,
      arabinose, xylose, and ribose, were derivatized with L-tryptophanamide (L-TrpNH2
      ) under alkaline conditions. Using a basic mobile phase (pH 9.2), the three
      aldohexoses or the three aldopentoses were simultaneously enantioseparated,
      respectively, but all the six monosaccharides could not be simultaneously
      enantioseparated. A large amount of nonreacted L-TrpNH2 was detected after the
      derivatized monosaccharides. In order to widen the separation window, a large
      portion of nonreacted L-TrpNH2 could be eliminated by liquid-liquid extraction
      with ethylacetate, and elution order of the derivatized monosaccharides and
      nonreacted L-TrpNH2 was found to be reversed using a neutral mobile phase. All of
      the six monosaccharides were simultaneously enantioseparated by reversed phase
      high-performance liquid chromatography (HPLC) using InertSustainSwift C18 column
      (4.6 mm i.d. * 150 mm) and a mobile phase containing 180 mM phosphate buffer (pH
      7.6), 1.5 mM butylboronic acid, and 5% acetonitrile at 40  degrees C.
      Nomenclature of D and L for monosaccharides is based on the configurations of the
      asymmetric C4 center for aldopentoses and C5 center for aldohexoses. It was found
      that the enantiomer elution order of these six monosaccharides and fucose in the
      proposed method conformed to be the absolute configuration of the C2 center.

PMID- 25994511
TI  - Chronological changes in stenosis of translocated coronary arteries on
      angiography after the arterial switch operation in children with transposition of
      the great arteries: comparison of myocardial scintigraphy and angiographic
      findings.
AB  - BACKGROUND: The peri-operative mortality of the arterial switch operation in
      neonates with transposition of the great arteries is considerably low; however,
      long-term outcomes of translocated coronary arteries still remain one of the most
      crucial issues. Methods and results A total of 110 neonates with transposition of
      the great arteries after arterial switch operation were evaluated; three (2.7%)
      late deaths occurred. The remaining 107 patients except for one underwent follow
      up angiography. Angiography showed coronary artery stenosis in nine (8.4%), with
      right coronary artery lesions in two and left main trunk lesions in seven. In two
      patients, right coronary artery stenosis regressed during follow-up. In left main
      trunk lesions, the severity of stenosis improved in four, did not change in one,
      and progressed to total occlusion in two patients. In children with coronary
      artery stenosis, myocardial scintigraphy showed perfusion defects in five out of
      six (83%) with left main trunk with ?75% stenosis and in four out of four with
      left main trunk stenosis ?90%. In contrast, patients whose coronary artery
      stenosis disappeared during follow-up had no perfusion defects on scintigraphy.
      CONCLUSIONS: Regression of ostial stenosis of the transplanted coronary artery on
      angiogram was observed. The stenosis regressed over time in six patients; two
      coronary arteries with 99% stenosis and delayed angiographic enhancement of the
      distal coronary artery resulted in total occlusion within 1 year after the
      arterial switch operation. Combination of angiography and myocardial scintigraphy
      could be useful to differentiate deceptive stenosis from progressive stenosis.

PMID- 25994512
TI  - Synthesis, structure and reactivity of [15]-macrodilactones.
AB  - A strategy for utilizing parameters such as the ring size, planar units and the
      connections between them, and the location of asymmetric centers has been applied
      to the design and synthesis of a new class of 15-membered macrocycles. The
      interplay between three planar units in combination with a hinge atom and a
      stereogenic center, introduces a planar chirality that defines the molecular
      topology of these [15]-macrodilactones. 

PMID- 25994513
TI  - Extra-glycaemic properties of empagliflozin.
AB  - Type 2 diabetes is a complex and multifaceted disease requiring an individualized
      approach. A special attention, in treating the patients, should be devoted to the
      presence of comorbidities like overweight or obesity and arterial hypertension.
      Among the available anti-hyperglycaemic agents, several are associated with side
      effects like hypoglycaemia and weight gain. An increasing interest is reported in
      sodium-glucose co-transporter-2 inhibitors, a relatively novel class of glucose
      lowering drugs that act independently of insulin, provide benefits beyond glucose
      lowering actions and show a better tolerability compared with traditional
      medications for type 2 diabetes. This review tries to offer a balanced view on
      the main extra-glycaemic effects of empagliflozin, also mentioning clinical data
      obtained with other sodium-glucose co-transporter-2 inhibitors; the role of the
      proximal tubule in the pathophysiology of diabetic nephropathy and the potential
      nehroprotection exerted by this compound are also briefly discussed.

PMID- 25994514
TI  - Controlled in situ reaction for the assembly of Cu(II) mixed-ligand coordination
      polymers: synthesis, structure, mechanistic insights, magnetism and catalysis.
AB  - It has been a challenge to decipher the in situ ligand reaction mechanism in
      assembly processes, involving metals and ligands. The present study shows two
      crystalline mixed-ligand Cu(II) coordination polymers isolated by controlled in
      situ ligand reactions under the same hydrothermal conditions. Two closely related
      examples provide a precious chance to access the in-depth mechanistic issues
      surrounding in situ reactions. The solid structure of 1 demonstrated that maleic
      acid was completely transformed to malic acid, whereas when fumaric acid was used
      in the same reaction conditions, an incomplete transformation from fumaric acid
      to malic acid was observed in the solid structure of 2. Compound 1 exhibits a 3D
      6-connected sni network based on a binuclear copper(ii) secondary building unit,
      whereas the 3D network of 2 is classified to a (6,8)-connected topology network.
      The difference in steric hindrance between maleic acid and fumaric acid dictates
      the degree of the in situ nucleophilic addition reaction. The comparison of
      synthesis and final solid structures indicates that the one-step nucleophilic
      addition mechanism for in situ generated malic acid under the current reaction
      conditions of 1 is plausible. The magnetic sensitivity measurements of 1
      demonstrated that overall antiferromagnetic coupling exists between Cu1 and Cu2
      ions and between Cu3 and Cu4 ions. Furthermore, the obtained 1 can be an active
      catalyst for the solvent-free silylcyanation of aromatic aldehydes under mild
      conditions.

PMID- 25994509
TI  - Gene * dietary pattern interactions in obesity: analysis of up to 68 317 adults
      of European ancestry.
AB  - Obesity is highly heritable. Genetic variants showing robust associations with
      obesity traits have been identified through genome-wide association studies. We
      investigated whether a composite score representing healthy diet modifies
      associations of these variants with obesity traits. Totally, 32 body mass index
      (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms
      were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of
      European ancestry (n = 68 317). Diet score was calculated based on self-reported
      intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and
      red/processed meats, sweets, sugar-sweetened beverages and fried potatoes
      (unfavorable). Multivariable adjusted, linear regression within each cohort
      followed by inverse variance-weighted, fixed-effects meta-analysis was used to
      characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b)
      diet score modification of genetic associations with BMI and BMI-adjusted WHR.
      Nominally significant interactions (P = 0.006-0.04) were observed between the
      diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1
      rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the
      respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these
      select interactions were small, our data indicated that associations between
      genetic predisposition and obesity traits were stronger with a healthier diet.
      Our findings generate interesting hypotheses; however, experimental and
      functional studies are needed to determine their clinical relevance. 

PMID- 25994515
TI  - Knee extension torque variability after exercise in ACL reconstructed knees.
AB  - The purpose of this study was to compare knee extension torque variability in
      patients with ACL reconstructed knees before and after exercise. Thirty two
      patients with an ACL reconstructed knee (ACL-R group) and 32 healthy controls
      (control group) completed measures of maximal isometric knee extension torque (90
      degrees  flexion) at baseline and following a 30-min exercise protocol (post
      exercise). Exercise included 30-min of repeated cycles of inclined treadmill
      walking and hopping tasks. Dependent variables were the coefficient of variation
      (CV) and raw-change in CV (DeltaCV): CV = (torque standard deviation/torque mean
      x 100), DeltaCV = (post-exercise - baseline). There was a group-by-time
      interaction (p = 0.03) on CV. The ACL-R group demonstrated greater CV than the
      control group at baseline (ACL-R = 1.07 +/- 0.55, control = 0.79 +/- 0.42, p =
      0.03) and post-exercise (ACL-R = 1.60 +/- 0.91, control = 0.94 +/- 0.41, p =
      0.001). DeltaCV was greater (p = 0.03) in the ACL-R group (0.52 +/- 0.82) than
      control group (0.15 +/- 0.46). CV significantly increased from baseline to post
      exercise (p = 0.001) in the ACL-R group, while the control group did not (p =
      0.06). The ACL-R group demonstrated greater knee extension torque variability
      than the control group. Exercise increased torque variability more in the ACL-R
      group than control group.

PMID- 25994516
TI  - Percutaneous Irreversible Electroporation of Unresectable Hilar
      Cholangiocarcinoma (Klatskin Tumor): A Case Report.
AB  - Irreversible electroporation (IRE) is a novel image-guided ablation technique
      that is rapidly gaining popularity in the treatment of malignant tumors located
      near large vessels or bile ducts. The presence of metal objects in the ablation
      zone, such as Wallstents, is generally considered a contraindication for IRE,
      because tissue heating due to power conduction may lead to thermal complications.
      This report describes a 66-year-old female with a Bismuth-Corlette stage IV
      unresectable cholangiocarcinoma with a metallic Wallstent in the common bile
      duct, who was safely treated with percutaneous IRE with no signs for relapse 1
      year after the procedure.

PMID- 25994517
TI  - Visualization of large elongated DNA molecules.
AB  - Long and linear DNA molecules are the mainstream single-molecule analytes for a
      variety of biochemical analysis within microfluidic devices, including
      functionalized surfaces and nanostructures. However, for biochemical analysis,
      large DNA molecules have to be unraveled, elongated, and visualized to obtain
      biochemical and genomic information. To date, elongated DNA molecules have been
      exploited in the development of a number of genome analysis systems as well as
      for the study of polymer physics due to the advantage of direct visualization of
      single DNA molecule. Moreover, each single DNA molecule provides individual
      information, which makes it useful for stochastic event analysis. Therefore,
      numerous studies of enzymatic random motions have been performed on a large
      elongated DNA molecule. In this review, we introduce mechanisms to elongate DNA
      molecules using microfluidics and nanostructures in the beginning. Secondly, we
      discuss how elongated DNA molecules have been utilized to obtain biochemical and
      genomic information by direct visualization of DNA molecules. Finally, we
      reviewed the approaches used to study the interaction of proteins and large DNA
      molecules. Although DNA-protein interactions have been investigated for many
      decades, it is noticeable that there have been significant achievements for the
      last five years. Therefore, we focus mainly on recent developments for monitoring
      enzymatic activity on large elongated DNA molecules. 

PMID- 25994518
TI  - Nowhere to hide: interrogating different metabolic parameters of Plasmodium
      falciparum gametocytes in a transmission blocking drug discovery pipeline towards
      malaria elimination.
AB  - BACKGROUND: The discovery of malaria transmission-blocking compounds is seen as
      key to malaria elimination strategies and gametocyte-screening platforms are
      critical filters to identify active molecules. However, unlike asexual parasite
      assays measuring parasite proliferation, greater variability in end-point readout
      exists between different gametocytocidal assays. This is compounded by
      difficulties in routinely producing viable, functional and stage-specific
      gametocyte populations. Here, a parallel evaluation of four assay platforms on
      the same gametocyte populations was performed for the first time. This allowed
      the direct comparison of the ability of different assay platforms to detect
      compounds with gametocytocidal activity and revealed caveats in some assay
      readouts that interrogate different parasite biological functions. METHODS:
      Gametocytogenesis from Plasmodium falciparum (NF54) was optimized with a robust
      and standardized protocol. ATP, pLDH, luciferase reporter and PrestoBlue(r)
      assays were compared in context of a set of 10 reference compounds. The assays
      were performed in parallel on the same gametocyte preparation (except for
      luciferase reporter lines) using the same drug preparations (48 h). The remaining
      parameters for each assay were all comparable. RESULTS: A highly robust method
      for generating viable and functional gametocytes was developed and
      comprehensively validated resulting in an average gametocytaemia of 4%.
      Subsequent parallel assays for gametocytocidal activity indicated that different
      assay platforms were not able to screen compounds with variant chemical scaffolds
      similarly. Luciferase reporter assays revealed that synchronized stage-specific
      gametocyte production is essential for drug discovery, as differential
      susceptibility in various gametocyte developmental populations is evident.
      CONCLUSIONS: With this study, the key parameters for assays aiming at testing the
      gametocytocidal activity of potential transmission blocking molecules against
      Plasmodium gametocytes were accurately dissected. This first and uniquely
      comparative study emphasizes differential effects seen with the use of different
      assay platforms interrogating variant biological systems. Whilst this data is
      informative from a biological perspective and may provide indications of the drug
      mode of action, it does highlight the care that must be taken when screening
      broad-diversity chemotypes with a single assay platform against gametocytes for
      which the biology is not clearly understood.

PMID- 25994520
TI  - Laryngeal spindle cell carcinoma: A population-based analysis of incidence and
      survival.
AB  - OBJECTIVES/HYPOTHESIS: Laryngeal spindle cell carcinoma (LSpCC) is a rare variant
      of squamous cell carcinoma. Surgery is the reported mainstay of treatment, but
      previous analyses failed to demonstrate survival outcomes by therapeutic
      modality. This study aims to carry out the largest population-based analysis of
      this histology to determine tumor characteristics, incidence, survival, and
      prognostic indicators. METHODS: The National Cancer Institute's Surveillance,
      Epidemiology, and End Results database was queried for cases of LSpCC diagnosed
      between 1973 and 2011. Data was analyzed for patient demographics, incidence,
      treatment, and survival. RESULTS: A total of 312 cases of LSpCC were identified.
      Males comprised 87.2% of the cases, representing a male-to-female ratio of nearly
      7:1. Whites accounted for 83.7% of LSpCC cases, whereas blacks represented 13.1%.
      Most cases (72.1%) arose in the glottis. The incidence of LSpCC from 2000 to 2011
      was 0.023 per 100,000, with an annual percent change of -0.115%. One-, 5-, and 10
      year disease-specific survival (DSS) rates for LSpCC were 90.9%, 74.1%, and
      57.9%; whereas 1-, 5-, and 10-year relative survival rates were 91.0%, 77.7%, and
      64.5%, respectively. Tumors of the glottis had a 5-year DSS of 84.0% compared to
      51.9% for nonglottic tumors (P < 0.0001). High-stage (III/IV) LpSCC had lower 5
      year DSS than low-stage (I/II) (36.8% and 91.8%, respectively) (P < 0.0001).
      Surgery imparted favorable 5-year survival, whereas radiotherapy did not impact
      survival rates. CONCLUSIONS: Laryngeal spindle cell carcinoma most commonly
      affects males and has a strong predilection for the glottis. Survival is best for
      glottic LSpCC. Surgery imparts a favorable prognosis compared to radiotherapy.
      LEVEL OF EVIDENCE: 4.

PMID- 25994521
TI  - Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to
      enhance TAP-independent presentation and immunogenicity.
AB  - Oncolytic adenoviruses can promote immune responses against tumors by expressing
      and/or displaying tumor-associated antigens. However, the strong immunodominance
      of viral antigens mask responses against tumor epitopes. In addition, defects in
      major histocompatibility complex class I antigen presentation pathway such as the
      downregulation of the transporter-associated with antigen processing (TAP) are
      frequently associated with immune evasion of tumor cells. To promote the
      immunogenicity of exogenous epitopes in the context of an oncolytic adenovirus,
      we have taken advantage of the ER localization of the viral protein E3-19K. We
      have inserted tumor-associated epitopes after the N-terminal signal sequence for
      membrane insertion of this protein and flanked them with linkers cleavable by the
      protease furin to facilitate their TAP-independent presentation. This strategy
      allowed an enhanced presentation of the exogenous epitopes in TAP-deficient tumor
      cells in vitro and the generation of higher specific immune responses in vivo
      that were able to significantly control tumor growth.

PMID- 25994523
TI  - Special issue: Neural basis of adaptive control.

PMID- 25994522
TI  - Proteomic analysis of the excretory/secretory products and antigenic proteins of
      Echinococcus granulosus adult worms from infected dogs.
AB  - BACKGROUND: Cystic echinococcosis, which is caused by Echinococcus granulosus, is
      one of the most widespread zoonotic helminth diseases that affects humans and
      livestock. Dogs, which harbor adult worms in their small intestines, are a
      pivotal source of E. granulosus infection in humans and domestic animals.
      Therefore, novel molecular approaches for the prevention and diagnosis of this
      parasite infection in dogs need to be developed. RESULTS: In this study, we
      performed proteomic analysis to identify excretory/secretory products (ES) and
      antigenic proteins of E. granulosus adult worms using two-dimensional
      electrophoresis, tandem matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF/TOF), and Western blotting of sera from infected dogs. This
      study identified 33 ES product spots corresponding to 9 different proteins and 21
      antigenic protein spots corresponding to 13 different proteins. Six antigenic
      proteins were identified for the first time. CONCLUSIONS: The present study
      extended the existing proteomic data of E. granulosus and provides further
      information regarding host-parasite interactions and survival mechanisms. The
      results of this study contribute to vaccination and immunodiagnoses for E.
      granulosus infections.

PMID- 25994524
TI  - Severe neutropenia in children after renal transplantation: incidence, course,
      and treatment with granulocyte colony-stimulating factor.
AB  - BACKGROUND: Infections are an important cause of morbidity and mortality in solid
      organ transplant recipients. Neutrophils play a crucial role in the initial host
      defense against bacterial pathogens. Neutropenia is not uncommon after renal
      transplantation in adults; however, there are scarce published data in children.
      We conducted a historical cohort study to evaluate the incidence, clinical
      course, and management of severe neutropenia after renal transplantation in
      children. METHODS: In a single-center study, we collected clinical and laboratory
      data on all children (<20 years) who underwent renal transplantation from January
      2005 to March 2014. All post-transplantation blood counts were reviewed; the
      lowest absolute neutrophil count was recorded and correlated with clinical
      information and other laboratory findings. RESULTS: Of the 72 patients studied,
      46 (64%) had at least one episode of neutropenia [absolute neutrophil count (ANC)
      <1500/MUl] during the study period, 16 of whom (22%) had severe neutropenia (ANC
      < 500/MUl), 2-11 months (median, 3.5) after renal transplantation. Work-up for
      viral infection or malignancy was performed. Initial management included dose
      decrease and subsequent discontinuation of antimetabolite, stopping co
      trimoxazole and valganciclovir. Bone marrow aspiration in four children revealed
      normal marrow cellularity in all cases, with myelocyte maturational arrest in
      two. Eight children (11%) were treated with granulocyte colony-stimulating factor
      (G-CSF) (5 mcg/kg/day) 1-4 doses (median, 2), with excellent response in all and
      no adverse effects. Eight children presented with fever during severe
      neutropenia, and were treated with empiric antibiotics.
      Mycophenolate/azathioprine were resumed in all patients unless contraindicated
      (pre-existing BK viremia -1, PTLD -1). Recurrence of neutropenia was seen in five
      patients, only one of whom required further treatment with G-CSF. Graft function
      was preserved during and after resolution of neutropenia. Post-transplant
      neutropenia in children is common, and mostly occurs in the first few months. Its
      etiology is probably primarily a result of the combination of immunosuppressive
      agents and prophylactic treatment of infections in the early post-transplant
      period. CONCLUSIONS: Decreasing immunosuppressive or antimicrobial medications
      carries the risk of acute rejection or infection. Off-label treatment with G-CSF
      may present a safe and effective alternative.

PMID- 25994526
TI  - Risk assessment: Physicians discuss motivations for rising rates of prophylactic
      mastectomies.

PMID- 25994525
TI  - Tracing the dynamic life story of a Bronze Age Female.
AB  - Ancient human mobility at the individual level is conventionally studied by the
      diverse application of suitable techniques (e.g. aDNA, radiogenic strontium
      isotopes, as well as oxygen and lead isotopes) to either hard and/or soft
      tissues. However, the limited preservation of coexisting hard and soft human
      tissues hampers the possibilities of investigating high-resolution diachronic
      mobility periods in the life of a single individual. Here, we present the results
      of a multidisciplinary study of an exceptionally well preserved circa 3.400-year
      old Danish Bronze Age female find, known as the Egtved Girl. We applied
      biomolecular, biochemical and geochemical analyses to reconstruct her mobility
      and diet. We demonstrate that she originated from a place outside present day
      Denmark (the island of Bornholm excluded), and that she travelled back and forth
      over large distances during the final months of her life, while consuming a
      terrestrial diet with intervals of reduced protein intake. We also provide
      evidence that all her garments were made of non-locally produced wool. Our study
      advocates the huge potential of combining biomolecular and biogeochemical
      provenance tracer analyses to hard and soft tissues of a single ancient
      individual for the reconstruction of high-resolution human mobility. 

PMID- 25994527
TI  - ACS publishes 2nd edition of Cancer Atlas.

PMID- 25994528
TI  - AACR, ASCO issue statement on E-cigarette regulation.

PMID- 25994530
TI  - Implant-supported rehabilitation after treatment of atrophic mandibular
      fractures: report of two cases.
AB  - OBJECTIVE: The objective of this article is to present options of rehabilitation
      with dental implants in two cases of severely atrophic mandibles (<10 mm) after
      rigid internal fixation of fractures. PATIENTS AND METHOD: Two patients who
      sustained fractures in severely atrophic mandibles with less than 10 mm of bone
      height were treated by open reduction and internal fixation through a
      transcervical access. Internal fixation was obtained with 2.4-mm locking
      reconstruction plates. The first patient presented satisfactory bone height at
      the area between the mental foramens and after 2 years, received flapless guided
      implants in the anterior mandible and an immediate protocol prosthesis. The
      second patient received a tent pole iliac crest autogenous graft after 2 years of
      fracture treatment and immediate implants. After 5 months, a protocol prosthesis
      was installed in the second patient. RESULTS: In both cases, the internal
      fixation followed AO principles for load-bearing osteosynthesis. Both prosthetic
      devices were Branemark protocol prosthesis. The mandibular reconstruction plates
      were not removed. Both patients are rehabilitated without complications and
      satisfied with esthetic and functional results. CONCLUSION: With the current
      techniques of internal fixation, grafting, and guided implants, the treatment of
      atrophic mandible fractures can achieve very good results, which were previously
      not possible.

PMID- 25994531
TI  - Biological activity of natural sesquiterpenoids containing a gem
      dimethylcyclopropane unit.
AB  - The biological activities of aristolane, aromadendrane, ent-1,10
      secoaromadendrane, 2,3-secoaromadendrane, ent-5,10-cycloaromadendrane,
      bicyclogermacrene, lepidozane, and maaliane terpenoids which contain the gem
      dimethylcyclopropyl unit are described. Particular attention is given to their
      anti-viral, anti-microbial and cytotoxic activities. In the main text there are
      119 references covering the literature from 1963-2014. The ESI contains tables
      listing 332 of these terpenoids, their occurrence and biological activity
      together with the related references.

PMID- 25994532
TI  - Childhood attention-deficit/hyperactivity disorder.

PMID- 25994535
TI  - [Early palliative care].
AB  - Early palliative care is a new intervention model that is increasingly used for
      patients with advanced chronic degenerative conditions. It has been shown to be
      effective in improving patients' quality of life and disease awareness and
      providing guidance and support in deciding on treatment choices, with significant
      cost savings for the healthcare system due to increased appropriateness of care.
      Several randomized controlled trials have demonstrated the efficacy of early
      palliative care, in particular in cancer patients and, more recently, also in
      patients with other advanced life-threatening illnesses. Results have been
      consistent in showing that early palliative care improves quality of life without
      negatively affecting survival compared with more aggressive treatment options.
      Palliative care should be delivered through an integrated approach to care that
      recognizes the roles of both general practitioners and hospital-based specialists
      for the early identification of patients who may most benefit from this
      intervention. 

PMID- 25994536
TI  - [Patient engagement in health care. New perspectives in oncology].
AB  - During the last decade, an increasing number of studies has been focused on
      patient engagement programs through which patients can be effective and informed
      managers of their health and health care. Based on our recent review, studies
      examining the nature of patient participation in service planning have found that
      most activities are limited to various forms of consultation, rather than the
      interactive partnerships advocated for treatment decision-making. Despite this
      clear evidence, many people want to play an active role in their own healthcare.
      They want to know how to protect and improve their health when they are well; and
      when they are ill, they want information about treatment options and likely
      outcomes. Consistent with these considerations, this paper intends to underline
      the importance to engage patients, to describe some different interventions to
      make patient effective informed; and, finally, to show some pilot projects from
      around the world, with a special focus on cancer care service of Ontario. 

PMID- 25994537
TI  - [Treatment of pancreatic cancer. Actuality and perspective].
AB  - Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest solid
      malignancies, with an extremely poor prognosis, with a 1-year survival rate of
      approximately 20%. Low survival rates of PDAC mainly derive from late diagnosis,
      with only a minority of patients amenable to surgery, as well as high rates of
      relapse and lack of effective treatments for advanced disease stages. As a
      result, there is an urgent need for the development of new effective therapies.
      At present, the greatest step towards an improvement of treatment has been made
      with the introduction of two combination chemotherapy regimens, namely FOLFIRINOX
      (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab
      paclitaxel. However, current research is also taking a multidirectional approach
      aiming at developing new treatment options, such as the use of agents targeting
      the oncogenic network signaling of KRAS or the extracellular matrix, as well as
      immune therapies. 

PMID- 25994538
TI  - [Therapeutic decisions and treatment with sorafenib in hepatocellular carcinoma:
      final analysis of GIDEON study in Italy].
AB  - INTRODUCTION: Sorafenib, an oral multikinase inhibitor, is the only targeted
      agent approved for the treatment of patients with hepatocellular carcinoma (HCC)
      after demonstration to increase overall survival compared to placebo in two
      randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions
      in HCC and Of its treatment with sorafeNib) is the largest, global, non
      interventional, prospective study of patients with uHCC (n>3200) treated with
      sorafenib in real-life clinical practice conditions. Here we report the final
      analysis of safety and efficacy in the Italian cohort of patients. METHODS:
      Patients with unresectable HCC who are candidates for systemic therapy, and for
      whom a decision has been made to treat with sorafenib, are eligible for
      inclusion. Patients demographics disease characteristics and treatment history
      were recorded at baseline visit. Sorafenib dose, concomitant medications,
      performance status, liver function, adverse events and efficacy (survival and
      response rate) were collected throughout the study. RESULTS: In the Italian
      cohort of the GIDEON study 278 patients were included in 36 centers. The global
      rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of
      grade 1 and 2, and only 8% were classified as serious. The most common were
      diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%),
      hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall
      survival was 14.4 months and time to progression 6.2 months. Objective responses
      were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases
      of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease
      control rate. DISCUSSION: The safety profile of sorafenib in terms of rate and
      type of adverse events is similar to that emerged in the global international
      GIDEON study as well as in the pivotal registration studies.

PMID- 25994540
TI  - [For a cinema not yet sated. On My mother, Nanni Moretti, <BR> the emperor of
      evil becomes a documentary film].

PMID- 25994539
TI  - [PARAMOUNT trial: clinical meaning of continuous maintenance therapy in lung
      cancer].
AB  - Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer
      related deaths worldwide across both sex. Patients with Advanced -NSCLC (A-NSCLC)
      do not have curative treatment options, so the primary endpoint of every
      therapeutic decision aims to prolong survival, improving or maintain a good
      Quality of Life (QoL). Histology could represent a positive predictive factor for
      patients with Non squamous NSCLC (Nsq-NSCLC) respect to pemetrexed treatment.
      Pemetrexed is an antifolate that inhibits primarily thymidylate synthase (TS),
      together with dihydrofolate reductase and glycinamide ribonucleotide formyl
      transferase. Pemetrexed in combination with cisplatin is approved in the first
      line setting and as monotherapy in the switch or continuous maintenance of Non
      Squamous A-NSCLC. Maintenance therapy is a widely used therapeutic option in
      other solid and hematologic malignancies, but in the A-NSCLC represent an
      innovative approach. The rationale in this new setting of patients is based on
      the evidence that patients who benefit from an initial induction therapy platinum
      based may benefit from maintenance therapy with the third generation agent
      dropping the platinum drug after four to six cycles. We can define two types of
      maintenance therapy: continuation maintenance and switch maintenance. Major
      results in prolonging Overall Survival (OS) was reported with the continuation
      maintenance strategy as in the PARAMOUNT trial. 

PMID- 25994541
TI  - [From scratch].

PMID- 25994542
TI  - [Sequential inhibition of angiogenesis in metastatic colorectal cancer: activity
      and efficacy of aflibercept].
AB  - We report a case of a young adult affected by an adenocarcinoma of the ascending
      colon with synchronous, unresectable liver metastases, diagnosed on April, 2011.
      The patient received a first-line of bio-chemotherapy with standard folfox
      regimen in association with bevacizumab. Deriving from which a good partial
      remission of the disease with its conversion to operability; so he underwent a
      right hemicolectomy with liver metastasectomy. Eleven months after radical
      surgery, the patient experimented an intrahepatic progression of the tumour, so
      he started a second-line therapy with FOLFIRI regimen plus aflibercept. Six
      months later than the beginning of the treatment he underwent a second liver
      metastasectomy. He subsequently received further twelve months of the same
      regimen. The patient is still alive forty-six months later than the diagnosis of
      the disease, expressing a good performance status and he's on fourth-line
      chemotherapy due to a relapse of its tumour. 

PMID- 25994544
TI  - The 11th International Conference on Brain Energy Metabolism "how energy
      metabolism shapes brain function". Preface.

PMID- 25994543
TI  - Pegylated liposomal doxorubicin (Lipo-Dox(r)) combined with cyclophosphamide and
      5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated
      metastatic breast cancer: an open-label, multi-center, non-comparative phase II
      study.
AB  - BACKGROUND: Anthracycline and taxane are classes of drugs that are frequently
      used in the adjuvant and palliative settings of metastatic breast cancer (MBC);
      however, treatment failure occurs in most cases. Limited data demonstrated
      favorable response in MBC after previous taxane-based treatment. The aim of this
      study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin
      (Lipo-Dox(r)) used as part of a combination salvage therapy for patients with MBC
      whose tumors progressed during or after taxane-based treatment. METHODS: Patients
      with MBC who failed to respond to previous taxane-based treatments were
      recruited. Treatment with pegylated liposomal doxorubicin (40 mg/m(2)),
      cyclophosphamide (500 mg/m(2)), and 5-fluorouracil (500 mg/m(2)) was administered
      every 3 weeks. Tumor response to treatment was determined by using the Response
      Evaluation Criteria in Solid Tumor criteria version 1.0, and left ventricular
      ejection fraction was measured before and after treatment using echocardiography.
      Each patient was followed for 30 days after the last dose of study medication or
      until resolution/stabilization of any drug-related adverse event. RESULTS: Forty
      five patients were recruited. As of December 2012, the median follow-up duration
      was 29.8 months, the overall response rate was 41.9 %, the median progression
      free survival was 8.2 months, and the median overall survival was 36.6 months for
      all treated patients. Grade 3/4 neutropenia, leucopenia, and neutropenic fever
      were observed in 14 %, 9 %, and 1 % of the cycles, respectively. Other non
      hematologic adverse effects were mild to moderate and were manageable. No
      decrease in left ventricular ejection function was noted. CONCLUSION: This
      regimen of combined of pegylated liposomal doxorubicin, cyclophosphamide, and 5
      fluorouracil exhibited a promising overall response rate, progression-free
      survival rate, and overall survival rate, with a safe cardiac toxicity profile
      and manageable adverse effects. This regimen could be considered as a treatment
      option for patients with MBC whose tumors progressed during or after taxane-based
      treatment.

PMID- 25994545
TI  - The genetic and environmental foundations of political, psychological, social,
      and economic behaviors: a panel study of twins and families.
AB  - Here we introduce the Genetic and Environmental Foundations of Political and
      Economic Behaviors: A Panel Study of Twins and Families (PIs Alford, Hatemi,
      Hibbing, Martin, and Smith). This study was designed to explore the genetic and
      environmental influences on social, economic, and political behaviors and
      attitudes. It involves identifying the psychological mechanisms that operate on
      these traits, the heritability of complex economic and political traits under
      varying conditions, and specific genetic correlates of attitudes and behaviors.
      In addition to describing the study, we conduct novel analyses on the data,
      estimating the heritability of two traits so far unexplored in the extant
      literature: Machiavellianism and Baron-Cohen's Empathizing Quotient. 

PMID- 25994548
TI  - The value of electrocardiographic abnormalities in the prognosis of pulmonary
      embolism: a consensus paper.
AB  - Electrocardiographic (ECG) abnormalities in the setting of acute pulmonary
      embolism (PE) are being increasingly characterized and mounting evidence suggests
      that ECG plays a valuable role in prognostication for PE. We review the
      historical 21-point ECG prognostic score for the severity of PE and examine the
      updated evidence surrounding the utility of ECG abnormalities in prognostication
      for severity of acute PE. We performed a literature search of MEDLINE, EMBASE,
      and PubMed up to February 2015. Article titles and abstracts were screened, and
      articles were included if they were observational studies that used a surface 12
      lead ECG as the instrument for measurement, a diagnosis of PE was confirmed by
      imaging, arteriography or autopsy, and analysis of prognostic outcomes was
      performed. Thirty-six articles met our inclusion criteria. We review the
      prognostic value of ECG abnormalities included in the 21-point ECG score,
      including new evidence that has arisen since the time of its publication. We also
      discuss the potential prognostic value of several ECG abnormalities with newly
      identified prognostic value in the setting of acute PE. 

PMID- 25994549
TI  - A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That
      Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized
      Phase Ib Live-Virus Challenge in Humans.
AB  - Current influenza vaccines elicit primarily antibody-based immunity. They require
      yearly revaccination and cannot be manufactured until the identification of the
      circulating viral strain(s). These issues remain to be addressed. Here we report
      a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity.
      Thirty-two males seronegative for the challenge virus by hemagglutination
      inhibition assay participated in this single-center, randomized, double-blind
      study. Volunteers received one dose of either the adjuvant alone (placebo, n =
      16) or FLU-v (500 MUg) and the adjuvant (n = 16), both in saline. Twenty-one days
      later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with
      influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety,
      tolerability, and cellular responses were assessed pre- and postvaccination.
      Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and
      well tolerated. No difference in the prevaccination FLU-v-specific gamma
      interferon (IFN-gamma) response was seen between groups (average +/- the standard
      error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold +/- 0.2
      fold and 1.6-fold +/- 0.5-fold higher than the negative-control value). Nineteen
      days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v
      specific IFN-gamma responses (8.2-fold +/- 3.9-fold versus 1.3-fold +/- 0.1-fold
      higher than the negative-control value [average +/- SEM] for FLU-v versus the
      placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with
      reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02)
      postchallenge. Increased cellular immunity specific to FLU-v correlates with
      reductions in both symptom scores and virus loads. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT01226758 and at
      hra.nhs.uk under EudraCT no. 2009-014716-35.). 

PMID- 25994550
TI  - Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to
      Borrelia burgdorferi 3 Months after a Tick Bite.
AB  - Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia
      burgdorferi. The most frequent clinical manifestation is a rash called erythema
      migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick
      bite are measured using enzyme-linked immunosorbent assays (ELISAs). One assay is
      based on native purified flagellum antigen (IgG), and the other assay is based on
      a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the
      time of a tick bite and 3 months later from 1,886 persons in Sweden and the Aland
      Islands, Finland. The seroconversion or relative change is defined by dividing
      the measurement units from the second sample by those from the first sample. The
      threshold for the minimum level of significant change was defined at the 2.5%
      level to represent the random error level. The thresholds were a 2.7-fold rise
      for the flagellar IgG assay and a 1.8-fold rise for the C6 assay. Of 1,886
      persons, 102/101 (5.4%) had a significant rise in antibody reactivity in the
      flagellar assay or the C6 assay. Among 40 cases with a diagnosis of Lyme
      borreliosis, the sensitivities corresponding to a rise in antibodies were 33% and
      50% for the flagellar antigen and the C6 antigen, respectively. Graphical methods
      to display the antibody response and to choose thresholds for a rise in relative
      antibody reactivity are shown and discussed. In conclusion, 5.4% of people with
      tick bites showed a rise in Borrelia-specific antibodies above the 2.5% threshold
      in either ELISA but only 40 (2.1%) developed clinical Lyme borreliosis. 

PMID- 25994551
TI  - fMRI measurements of amygdala activation are confounded by stimulus correlated
      signal fluctuation in nearby veins draining distant brain regions.
AB  - Imaging the amygdala with functional MRI is confounded by multiple averse
      factors, notably signal dropouts due to magnetic inhomogeneity and low signal-to
      noise ratio, making it difficult to obtain consistent activation patterns in this
      region. However, even when consistent signal changes are identified, they are
      likely to be due to nearby vessels, most notably the basal vein of rosenthal
      (BVR). Using an accelerated fMRI sequence with a high temporal resolution (TR =
      333 ms) combined with susceptibility-weighted imaging, we show how signal changes
      in the amygdala region can be related to a venous origin. This finding is
      confirmed here in both a conventional fMRI dataset (TR = 2000 ms) as well as in
      information of meta-analyses, implying that "amygdala activations" reported in
      typical fMRI studies are likely confounded by signals originating in the BVR
      rather than in the amygdala itself, thus raising concerns about many conclusions
      on the functioning of the amygdala that rely on fMRI evidence alone.

PMID- 25994552
TI  - Patterns of emergency department use for dental and oral health care:
      implications for dental and medical care coordination.
AB  - OBJECTIVES: To describe emergency department (ED) utilization for oral conditions
      (OCs) focusing on total volume, costs, repeat utilization, small area predictors,
      and implications for dental and medical care coordination. METHODS:
      Administrative and demographic data for New Jersey were used to identify users of
      the ED for OCs and a group of "high users," defined as individuals with four or
      more ED visits for OCs during 2008-2010. Cost-to-charge ratios were used to
      estimate costs, and linear regression models applied to zip codes were used to
      determine strongest predictors of small area variation in ED use for OCs.
      RESULTS: ED visits for OC generated $25.5 million in costs during 2008-2010. High
      users represented 4.2 percent of all users and 21.3 percent of ED visits for OCs.
      Almost all high users had a diagnosis of "dental disorder not otherwise
      specified," and tobacco use disorder was the most common comorbid medical
      condition. Young adults (ages 19-34), non-Hispanic blacks, and the medically
      uninsured were over-represented among high users. High users routinely spread
      their use across multiple hospitals (e.g., 40 percent of them visited three or
      more hospitals). Local dentist supply and ED use for other conditions were
      significant predictors of zip code-level ED use for OCs. CONCLUSIONS:
      Coordination of medical and dental treatment might improve health and reduce
      costs if targeted to high user populations. Health-care delivery reforms, such as
      accountable care organizations, could provide vehicles for achieving this
      coordination. Important challenges include fragmentation of ED visits across
      hospitals, adequacy of dentist supply, and broader reliance on the ED for health
      problems.

PMID- 25994553
TI  - Synthesis of benzothiophene-based hydroxamic acids as potent and selective HDAC6
      inhibitors.
AB  - A small library of 3-[(4-hydroxycarbamoylphenyl)aminomethyl]benzothiophenes was
      prepared and assessed as a novel class of HDAC6 inhibitors, leading to the
      identification of three representatives as potent and selective HDAC6 inhibitors.
      Further tests with regard to inflammatory responses indicated that HDAC6
      inhibition can be uncoupled from transcriptional inhibition at the level of
      activated NF-kappaB, AP-1, and GR. 

PMID- 25994555
TI  - Preparation of Highly Purified Stearidonic Acid from Echium Oil via an Enzymatic
      Method Combined with Preparative High Performance Liquid Chromatography.
AB  - Stearidonic acid (SDA), an n-3 polyunsaturated fatty acid (PUFA), can be obtained
      from plant origin oils and it can be a good source of PUFA for vegetarians. SDA
      can be easily converted to longer PUFA such as docosahexaenoic acid and
      eicosapentaenoic acid. Highly purified stearidonic acid (SDA) was prepared
      successfully from echium oil via an enzymatic method combined with preparative
      high performance liquid chromatography. In the 1(st) step, SDA enrichment was
      accomplished using Candida rugosa lipase and 39.5% of SDA was obtained in the
      fatty acid fraction. Subsequently, the 1(st) reaction mixture was used for the
      2(nd) enzymatic esterification without any separation process. The 2(nd)
      esterification was conducted for further SDA enrichment in a packed-bed reactor
      using Lipozyme RM IM from Rhizomucor miehei and the SDA content increased in a
      very short residence time. Ethanol was selected as an appropriate alcohol to
      react as an acyl receptor, and the other conditions for SDA enrichment were
      optimized at 20 degrees C of temperature, and 1:4 of molar ratio (i.e., fatty
      acid to ethanol). Under these conditions, 51.6% of SDA was obtained in the fatty
      acid fraction after a residence time of 15 min. Finally, highly purified SDA
      (purity, >99%) was obtained by prep-HPLC using the SDA-rich fraction obtained
      from the two-step lipase-catalyzed esterification. 

PMID- 25994554
TI  - Large-scale spatiotemporal spike patterning consistent with wave propagation in
      motor cortex.
AB  - Aggregate signals in cortex are known to be spatiotemporally organized as
      propagating waves across the cortical surface, but it remains unclear whether the
      same is true for spiking activity in individual neurons. Furthermore, the
      functional interactions between cortical neurons are well documented but their
      spatial arrangement on the cortical surface has been largely ignored. Here we use
      a functional network analysis to demonstrate that a subset of motor cortical
      neurons in non-human primates spatially coordinate their spiking activity in a
      manner that closely matches wave propagation measured in the beta oscillatory
      band of the local field potential. We also demonstrate that sequential spiking of
      pairs of neuron contains task-relevant information that peaks when the neurons
      are spatially oriented along the wave axis. We hypothesize that the spatial
      anisotropy of spike patterning may reflect the underlying organization of motor
      cortex and may be a general property shared by other cortical areas. 

PMID- 25994556
TI  - Detection of Butter Adulteration with Lard by Employing (1)H-NMR Spectroscopy and
      Multivariate Data Analysis.
AB  - The authentication of food products from the presence of non-allowed components
      for certain religion like lard is very important. In this study, we used proton
      Nuclear Magnetic Resonance ((1)H-NMR) spectroscopy for the analysis of butter
      adulterated with lard by simultaneously quantification of all proton bearing
      compounds, and consequently all relevant sample classes. Since the spectra
      obtained were too complex to be analyzed visually by the naked eyes, the
      classification of spectra was carried out.The multivariate calibration of partial
      least square (PLS) regression was used for modelling the relationship between
      actual value of lard and predicted value. The model yielded a highest regression
      coefficient (R(2)) of 0.998 and the lowest root mean square error calibration
      (RMSEC) of 0.0091% and root mean square error prediction (RMSEP) of 0.0090,
      respectively. Cross validation testing evaluates the predictive power of the
      model. PLS model was shown as good models as the intercept of R(2)Y and Q(2)Y
      were 0.0853 and -0.309, respectively. 

PMID- 25994557
TI  - Essential Oil from Clove Bud (Eugenia aromatica Kuntze) Inhibit Key Enzymes
      Relevant to the Management of Type-2 Diabetes and Some Pro-oxidant Induced Lipid
      Peroxidation in Rats Pancreas in vitro.
AB  - The inhibition of enzymes involved in the breakdown of carbohydrates is
      considered a therapeutic approach to the management of type-2 diabetes. This
      study sought to investigate the effects of essential oil from clove bud on alpha
      amylase and alpha-glucosidase activities. Essential oil from clove bud was
      extracted by hydrodistillation, dried with anhydrous Na2SO4 and characterized
      using gas chromatography-mass spectrometry (GC-MS). The effects of the essential
      oil on alpha-amylase and alpha-glucosidase activities were investigated. The
      antioxidant properties of the oil and the inhibition of Fe(2+) and sodium
      nitroprusside-induced malondialdehyde (MDA) production in rats pancreas
      homogenate were also carried out. The essential oil inhibited alpha-amylase
      (EC50=88.9 MUl/L) and alpha-glucosidase (EC50=71.94 MUl/L) activities in a dose
      dependent manner. Furthermore, the essential oil inhibited Fe(2+) and SNP-induced
      MDA production and exhibited antioxidant activities through their NO*, OH*,
      scavenging and Fe(2+)- chelating abilities. The total phenolic and flavonoid
      contents of the essential oil were 12.95 mg/g and 6.62 mg/g respectively. GC-MS
      analysis revealed the presence of alpha-pinene, beta-pinene, neral, geranial,
      gamma terpinene, cis-ocimene, allo ocimene, 1,8-cineole, linalool, borneol,
      myrcene and pinene-2-ol in significant amounts. Furthermore, the essential oils
      exhibited antioxidant activities as typified by hydroxyl (OH) and nitric oxide
      (NO)] radicals scavenging and Fe(2+)-chelating abilities. The inhibition of alpha
      amylase and alpha-glucosidase activities, inhibition of pro-oxidant induced lipid
      peroxidation in rat pancreas and antioxidant activities could be possible
      mechanisms for the use of the essential oil in the management and prevention of
      oxidative stress induced type-2 diabetes.

PMID- 25994558
TI  - Synthesis and Anti-microbial Activity of Novel Phosphatidylethanolamine-N-amino
      Acid Derivatives.
AB  - The study involved synthesis of five novel amino acid derivatives of
      phosphatidylethanolamine isolated from egg yolk lecithin employing a three step
      procedure i) N-protection of L-amino acids with BOC anhydride in alkaline medium
      ii) condensation of - CO2H group of N-protected amino acid with free -NH2 of PE
      by a peptide linkage and iii) deprotection of N-protected group of amino acids to
      obtain phosphatidylethanolamine-N-amino acid derivatives in 60-75% yield. The
      five L-amino acids used were L glycine, L-valine, L-leucine, L-isoleucine and L
      phenylalanine. The amino acid derivatives were screened for anti-baterial
      activity against B. subtilis, S. aureus, P. aeroginosa and E. coli taking
      Streptomycin as reference compound and anti-fungal activity against C. albicans,
      S. cervisiae, A. niger taking AmphotericinB as reference compound. All the amino
      acid derivatives exhibited extraordinary anti-bacterial activities about 3 folds
      or comparable to Streptomycin and moderate or no anti-fungal activity against
      Amphotericin-B. 

PMID- 25994559
TI  - Capsaicin inhibits the adipogenic differentiation of bone marrow mesenchymal stem
      cells by regulating cell proliferation, apoptosis, oxidative and nitrosative
      stress.
AB  - Obesity is a global health problem that requires the utmost attention. Apart from
      other factors the trans-differentiation of mesenchymal stem cells (MSCs) into
      adipocytes is an added detrimental factor causing the intensification of obesity.
      The main objective of this present study is to analyse whether capsaicin is
      capable of inhibiting the differentiation of BMSCs to adipocytes. Bone marrow
      mesenchymal stem cells (BMSCs) were obtained and exposed to different
      concentrations of capsaicin for a period of 6 days following 2 days of adipogenic
      induction. The capsaicin exposed cells were collected at three different time
      points (2, 4 and 6 days) and subjected to various analyses. BMSCs after exposure
      to capsaicin showed dose and time dependent reduction in cell viability and
      proliferation. Interestingly, capsaicin induced cell cycle arrest at G0-G1 and
      increased apoptosis by increasing reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) production. Capsaicin significantly inhibited the early
      adipogenic differentiation, lipogenesis and maturation of adipocytes with
      concomitant repression of PPARgamma, C/EBPalpha, FABP4 and SCD-1. Taken together,
      the results of the present study have clearly emphasized that capsaicin
      potentially inhibits the adipogenic differentiation of mesenchymal stem cells via
      many different pathways (anti-proliferative, apoptotic and cell cycle arrest)
      through the stimulation of ROS and RNS production. Thus, capsaicin not only
      suppresses the maturation of pre-adipocytes into adipocytes but also inhibits the
      differentiation of mesenchymal stem cells into adipocytes.

PMID- 25994560
TI  - Rearing and foraging affects bumblebee (Bombus terrestris) gut microbiota.
AB  - Bumblebees are ecologically and economically important as pollinators of crop and
      wild plants, especially in temperate systems. Species, such as the buff-tailed
      bumblebee (Bombus terrestris), are reared commercially to pollinate high-value
      crops. Their highly specific gut microbiota, characterized by low diversity, may
      affect nutrition and immunity and are likely to be important for fitness and
      colony health. However, little is known about how environmental factors affect
      bacterial community structure. We analysed the gut microbiota from three groups
      of worker bumblebees (B. terrestris) from distinct colonies that varied in
      rearing and foraging characteristics: commercially reared with restricted
      foraging (RR); commercially reared with outside foraging (RF); and wild-caught
      workers (W). Contrary to previous studies, which indicate that bacterial
      communities are highly conserved across workers, we found that RF individuals had
      an intermediate community structure compared with RR and W types. Further, this
      was shaped by differences in the abundances of common operational taxonomic units
      (OTUs) and the diversity of rare OTUs present, which we propose results from an
      increase in the variety of carbohydrates obtained through foraging. 

PMID- 25994561
TI  - Disease control and toxicity outcomes for T4 carcinoma of the nasopharynx treated
      with intensity-modulated radiotherapy.
AB  - BACKGROUND: Treatment of T4 nasopharyngeal carcinoma (NPC) is challenging because
      of the proximity of the tumor to the central nervous system. The purpose of this
      study was to present our evaluation of disease control and toxicity outcomes for
      patients with T4 NPC treated with intensity-modulated radiation therapy (IMRT)
      and chemotherapy. METHODS: The medical records of 66 patients with T4 NPC treated
      from 2002 to 2012 with IMRT were reviewed. Endpoints included tumor control and
      toxicity outcomes (Common Terminology Criteria for Adverse Events [CTCAE v4.0]).
      RESULTS: Median follow-up was 38 months. Five-year rates of locoregional control,
      distant metastasis-free survival, progression-free survival (PFS), and overall
      survival (OS) were 80%, 62%, 57%, and 69%, respectively. Nodal involvement was
      associated with worse PFS (p = .015). Gross target volume (GTV) volume >100 cm
      and planning target volume (PTV) volume >400 cm were associated with worse OS (p
      = .038 and p = .004, respectively). Four patients had significant cognitive
      impairment, and 9 had MRI evidence of brain necrosis. CONCLUSION: For patients
      with T4 NPC treated with IMRT and chemotherapy, survival and locoregional disease
      control rates have improved; however, late treatment toxicity remains a concern.
      (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E925-E933, 2016.

PMID- 25994562
TI  - Secretory breast carcinoma in a 6-year-old girl: mastectomy with sentinel lymph
      node dissection.
AB  - Secretory breast carcinoma (SBC) is a rare type of breast neoplasia that was
      originally described in children. SBC is an indolent breast tumor with good
      clinical outcome and rare systemic involvement. Since, majority of studies
      concerning pediatric SBC have been case reports, it has been difficult to clearly
      elucidate the characteristics and optimal treatment strategies for SBC in
      children. Although treatment recommendations vary, surgical excision is the
      primary mode of treatment. Also, necessity of axillary and/or sentinel lymph node
      dissection is another matter of discussion in children. We report a 6-year-old
      girl who was diagnosed as SBC was reported to discuss the use of mastectomy with
      sentinel lymph node dissection in the treatment of this rare tumor in children. 

PMID- 25994563
TI  - Banding the Right Ventricular Assist Device Outflow Conduit: Is It Really
      Necessary With Current Devices?
AB  - Implantable left ventricular assist devices (LVADs) have been adapted clinically
      for right-sided mechanical circulatory support (RVAD). Previous studies on RVAD
      support have established the benefits of outflow cannula restriction and
      rotational speed reduction, and recent literature has focused on assessing either
      the degree of outflow cannula restriction required to simulate left-sided
      afterload, or the limitation of RVAD rotational speeds. Anecdotally, the utility
      of outflow cannula restriction has been questioned, with suggestion that banding
      may be unnecessary and may be replaced simply by varying the outflow conduit
      length. Furthermore, many patients have a high pulmonary vascular resistance
      (PVR) at the time of ventricular assist device (VAD) insertion that reduces with
      pulmonary vascular bed remodeling. It is therefore important to assess the
      potential changes in flow through an RVAD as PVR changes. In this in vitro study,
      we observed the use of dual HeartWare HVAD devices (HeartWare Inc., Framingham,
      MA, USA) in biventricular support (BiVAD) configuration. We assessed the pumps'
      ability to maintain hemodynamic stability with and without banding; and with
      varying outflow cannulae length (20, 40, and 60 cm). Increased length of the
      outflow conduit was found to produce significantly increased afterload to the
      device, but this was not found to be necessary to maintain the device within the
      manufacturer's recommended operational parameters under a simulated normal
      physiological setting of mild and severe right ventricular (RV) failure. We
      hypothesize that 40 cm of outflow conduit, laid down along the diaphragm and then
      up over the RV to reach the pulmonary trunk, will generate sufficient resistance
      to maintain normal pump function. 

PMID- 25994564
TI  - Is achlorhydria a cause of iron deficiency anemia?
AB  - We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause
      of iron deficiency anemia (IDA) in humans. First, we analyzed the currently
      available research on the association between achlorhydria and IDA. When gastric
      acid secretion was measured after maximal stimulation, the frequency of
      achlorhydria (or severe hypochlorhydria) was 44% in patients with idiopathic IDA
      and 1.8% in healthy controls. In some patients with pernicious anemia, presumed
      achlorhydria preceded the development of IDA in time. However, we found no
      credible evidence that IDA caused gastritis or that IDA preceded the development
      of achlorhydria. Thus, correlational results favor achlorhydria as the causal
      factor in the association between achlorhydria and IDA. Second, we sought to
      determine whether gastritis and achlorhydria cause negative iron balance. When
      biosynthetic methods were used to isotopically label iron in food, achlorhydric
      patients were found to have severe malabsorption of nonheme iron, which persisted
      after the development of IDA. In 1 study, achlorhydria reduced the normal
      increase in heme-iron absorption from hemoglobin in response to iron deficiency.
      After an injection of isotopic iron into normal men, the physiologic loss of iron
      from the body was found to be 1 mg/d. Patients with chronic gastritis had excess
      fecal loss of isotopically tagged plasma iron. Calculations based on these
      results indicate that the absorption of iron from a typical Western diet by
      achlorhydric patients would be less than physiologic iron losses, creating a
      negative iron balance that could not be overcome by the adaptive increase in
      duodenal iron absorptive capacity that occurs in response to iron deficiency. The
      combination of results from these correlational and pathophysiologic studies
      supports the hypothesis that gastritis-induced achlorhydria can be an independent
      cause of IDA. 

PMID- 25994565
TI  - Beyond the sticker price: including and excluding time in comparing food prices.
AB  - BACKGROUND: An ongoing debate in the literature is how to measure the price of
      food. Most analyses have not considered the value of time in measuring the price
      of food. Whether or not the value of time is included in measuring the price of a
      food may have important implications for classifying foods based on their
      relative cost. OBJECTIVE: The purpose of this article is to compare prices that
      exclude time (time-exclusive price) with prices that include time (time-inclusive
      price) for 2 types of home foods: home foods using basic ingredients (home
      recipes) vs. home foods using more processed ingredients (processed recipes). The
      time-inclusive and time-exclusive prices are compared to determine whether the
      time-exclusive prices in isolation may mislead in drawing inferences regarding
      the relative prices of foods. DESIGN: We calculated the time-exclusive price and
      time-inclusive price of 100 home recipes and 143 processed recipes and then
      categorized them into 5 standard food groups: grains, proteins, vegetables,
      fruit, and dairy. We then examined the relation between the time-exclusive prices
      and the time-inclusive prices and dietary recommendations. RESULTS: For any food
      group, the processed food time-inclusive price was always less than the home
      recipe time-inclusive price, even if the processed food's time-exclusive price
      was more expensive. Time-inclusive prices for home recipes were especially higher
      for the more time-intensive food groups, such as grains, vegetables, and fruit,
      which are generally underconsumed relative to the guidelines. CONCLUSION:
      Focusing only on the sticker price of a food and ignoring the time cost may lead
      to different conclusions about relative prices and policy recommendations than
      when the time cost is included.

PMID- 25994566
TI  - Prospective association between alcohol intake and hormone-dependent cancer risk:
      modulation by dietary fiber intake.
AB  - BACKGROUND: Alcohol intake is associated with increased circulating
      concentrations of sex hormones, which in turn may increase hormone-dependent
      cancer risk. This association may be modulated by dietary fiber intake, which has
      been shown to decrease steroid hormone bioavailability (decreased blood
      concentration and increased sex hormone-binding globulin concentration). However,
      this potential modulation has not been investigated in any prospective cohort.
      OBJECTIVES: Our objectives were to study the relation between alcohol intake and
      the risk of hormone-dependent cancers (breast, prostate, ovarian, endometrial,
      and testicular) and to investigate whether dietary fiber intake modulated these
      associations. DESIGN: This prospective observational analysis included 3771 women
      and 2771 men who participated in the Supplementation en Vitamines et Mineraux
      Antioxydants study (1994-2007) and completed at least 6 valid 24-h dietary
      records during the first 2 y of follow-up. After a median follow-up of 12.1 y,
      297 incident hormone-dependent cancer cases, including 158 breast and 123
      prostate cancers, were diagnosed. Associations were tested via multivariate Cox
      proportional hazards models. RESULTS: Overall, alcohol intake was directly
      associated with the risk of hormone-dependent cancers (tertile 3 vs. tertile 1:
      HR: 1.36; 95% CI: 1.00, 1.84; P-trend = 0.02) and breast cancer (HR: 1.70; 95%
      CI: 1.11, 2.61; P-trend = 0.04) but not prostate cancer (P-trend = 0.3). In
      stratified analyses (by sex-specific median of dietary fiber intake), alcohol
      intake was directly associated with hormone-dependent cancer (tertile 3 vs.
      tertile 1: HR: 1.76; 95% CI: 1.10, 2.82; P-trend = 0.002), breast cancer (HR:
      2.53; 95% CI: 1.30, 4.95; P-trend = 0.02), and prostate cancer (HR: 1.37; 95% CI:
      0.65, 2.89; P-trend = 0.02) risk among individuals with low dietary fiber intake
      but not among their counterparts with higher dietary fiber intake (P-trend = 0.9,
      0.8, and 0.6, respectively). The P-interaction between alcohol and dietary fiber
      intake was statistically significant for prostate cancer (P = 0.01) but not for
      overall hormone-dependent (P = 0.2) or breast (P = 0.9) cancer. CONCLUSION: In
      line with mechanistic hypotheses and experimental data, this prospective study
      suggested that dietary fiber intake might modulate the association between
      alcohol intake and risk of hormone-dependent cancer. This trial was registered at
      clinicaltrials.gov as NCT00272428.

PMID- 25994567
TI  - Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy
      older adults.
AB  - BACKGROUND: Age-associated declines in muscle mass and function are major risk
      factors for an impaired ability to carry out activities of daily living, falls,
      prolonged recovery time after hospitalization, and mortality in older adults. New
      strategies that can slow the age-related loss of muscle mass and function are
      needed to help older adults maintain adequate performance status to reduce these
      risks and maintain independence. OBJECTIVE: We evaluated the efficacy of fish oil
      derived n-3 (omega-3) PUFA therapy to slow the age-associated loss of muscle mass
      and function. DESIGN: Sixty healthy 60-85-y-old men and women were randomly
      assigned to receive n-3 PUFA (n = 40) or corn oil (n = 20) therapy for 6 mo.
      Thigh muscle volume, handgrip strength, one-repetition maximum (1-RM) lower- and
      upper-body strength, and average power during isokinetic leg exercises were
      evaluated before and after treatment. RESULTS: Forty-four subjects completed the
      study [29 subjects (73%) in the n-3 PUFA group; 15 subjects (75%) in the control
      group]. Compared with the control group, 6 mo of n-3 PUFA therapy increased thigh
      muscle volume (3.6%; 95% CI: 0.2%, 7.0%), handgrip strength (2.3 kg; 95% CI: 0.8,
      3.7 kg), and 1-RM muscle strength (4.0%; 95% CI: 0.8%, 7.3%) (all P < 0.05) and
      tended to increase average isokinetic power (5.6%; 95% CI: -0.6%, 11.7%; P =
      0.075). CONCLUSION: Fish oil-derived n-3 PUFA therapy slows the normal decline in
      muscle mass and function in older adults and should be considered a therapeutic
      approach for preventing sarcopenia and maintaining physical independence in older
      adults. This study was registered at clinicaltrials.gov as NCT01308957.

PMID- 25994568
TI  - Anticoagulant therapy of cancer patients: Will patient selection increase overall
      survival?
AB  - Already since the early 1800s, it has been recognised that malignancies may
      provoke thromboembolic complications, and indeed cancer patients are at increased
      risk of developing venous thrombosis. Interestingly, case control studies of deep
      vein thrombosis suggested that low-molecular-weight heparin (LMWH) improved
      survival of cancer patients. This led to the hypothesis that cancer cells might
      'take advantage' of a hypercoagulable state to more efficiently metastasise.
      Initial randomised placebo control trials showed that LMWH improve overall
      survival of cancer patients, especially in those patients with a relatively good
      prognosis. The failure of recent phase III trials, however, tempers enthusiasm
      for anticoagulant treatment in cancer patients despite an overwhelming body of
      literature showing beneficial effects of anticoagulants in preclinical models.
      Instead of discarding LMWH as potential (co)treatment modality in cancer
      patients, these disappointing recent trials should guide future preclinical
      research on anticoagulants in cancer biology. Most and for all, the underlying
      mechanisms by which coagulation drives tumour progression need to be elucidated.
      This could ultimately allow selection of cancer patients most likely to benefit
      from anticoagulant treatment and/or from targeted therapy downstream of
      coagulation factor signalling. 

PMID- 25994569
TI  - FOXP4 modulates tumor growth and independently associates with miR-138 in non
      small cell lung cancer cells.
AB  - Family of forkhead box transcription factors, including forkhead box P4 (FOXP4),
      plays an important role in oncogenesis. The current study is to evaluate the role
      of FOXP4 in regulating human non-small cell lung cancer (NSCLC). Quantitative RT
      PCR and Western blot were performed to evaluate the gene and protein expressions
      of FOXP4 in six NSCLC cell lines and 55 NSCLC patients. Lentivirus of small
      hairpin RNA (FOXP4-shRNA) was used to downregulate FOXP4 in NSCLC cell lines A549
      and H1703 cells. Its effect on NSCLC growth, invasion, and cell cycle were
      evaluated by cell proliferation assay, migration assay, and cell cycle assay,
      respectively. Dual luciferase assay and Western blot were used to examine whether
      microRNA-138 (miR-138) was an upstream regulator of FOXP4. The dependence of
      FOXP4 on miR-138 associated signaling pathway was evaluated by ectopically
      overexpressing enhancer of zeste homolog 2 (EZH2), a known miR-138 target in
      NSCLC. FOXP4 was highly expressed in both NSCLC cell lines and NSCLC patients.
      FOXP4 downregulation by FOXP4-shRNA markedly reduced cancer cell growth and
      invasion, as well as induced cell cycle arrest in A549 and H1703 cells. MiR-138
      was confirmed to be an upstream regulator of FOXP4 and directly regulated FOXP4
      expression in A549 and H1703 cells. FOXP4 downregulation-mediated inhibition on
      cancer cell growth and invasion was independent on overexpressing EZH2, another
      direct target of miR-138 in NSCLC. Our data demonstrated that FOXP4 was a
      critical regulator in NSCLC and independently associated with miR-138 regulation.

PMID- 25994570
TI  - Transcriptome analysis of the cancer/testis genes, DAZ1, AURKC, and TEX101, in
      breast tumors and six breast cancer cell lines.
AB  - Breast cancer is the most frequent cancer with second mortality rate in women
      worldwide. Lack of validated biomarkers for early detection of breast cancer to
      warranty the diagnosis and effective treatments in early stages has directed to
      the new therapeutic approach. Cancer/testis antigens which have restricted normal
      expression in testis and aberrant expression in different cancers are promising
      targets for generating cancer vaccines, monoclonal antibodies, or dendritic cell
      based immunotherapy. In this context, we investigated the expression of two known
      cancer testis genes, Aurora kinase C (AURKC) and testis expressed 101 (TEX101),
      and one new candidate, deleted in azoospermia 1 (DAZ1), in six breast cancer cell
      lines including two ductal carcinomas, T47D and BT-474, and four adenocarcinomas,
      MDA-MB-231, MDA-MB-468, MCF7, and SKBR3 as well as 50 breast cancer tumors in
      comparison to normal mammary epithelial cells using quantitative real-time
      reverse transcription PCR (RT-PCR). Results showed significant overexpression (p
      = 0.000) of all three genes in BT474, DAZ1 in MDA-MB-231, and AURKC and DAZ1 in
      SKBR3 and significant downregulation (p = 0.000) of AURKC in MCF7 cell line
      relative to normal breast epithelial cells. Breast tumors showed significant
      overexpression of AURKC in comparison to normal breast tissues (p = 0.016). The
      results are noticeable especially in the case of AURKC; however, there is a
      little knowledge about the nature, causes, consequences, and effects of
      cancer/testis antigens activation in different cancers. It is suggested that
      AURKC has effects on cell division via its serin/threonin kinases activity and
      organizing microtubules in relation to centrosome/spindle function during
      mitosis.

PMID- 25994571
TI  - The prognostic impact of preoperative blood monocyte count in pathological T3N0M0
      rectal cancer without neoadjuvant chemoradiotherapy.
AB  - It remains controversial whether adjuvant therapy should be delivered to
      pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy. Thus
      identification of patients at high risk is of particular importance. Herein, we
      aimed to evaluate whether the absolute peripheral blood monocyte count can
      stratify the pathological T3N0M0M0 rectal cancer patients in survival. A total of
      270 pathological T3N0M0 rectal cancer patients with total mesorectal excision
      principle radical resection were included. The optimal cut-off value of
      preoperative monocyte count was determined by receiver operating characteristic
      curve analysis. Overall survival and disease-free survival between low- and high
      monocyte were estimated by Kaplan-Meier method and Cox regression model. The
      optimal cut-off value for monocyte count was 595 mm(3). In univariate analysis,
      patients with monocyte counts higher than 595/mm(3) had significantly inferior 5
      year overall survival (79.2 vs 94.2 %, P = 0.006) and disease-free survival (67.8
      vs 86.0 %, P < 0.001). With adjustment for the known covariates, monocyte count
      remained to be associated with poor overall survival (HR = 2.55, 95 % CI 1.27
      5.10; P = 0.008) and disease-free survival (HR = 2.63, 95 % CI 1.48-4.69; P =
      0.001). Additionally, the significant association of monocyte count with disease
      free survival was hardly influenced in the subgroup analysis, whereas this
      correlation was restricted to the males and patients with normal carcinoembryonic
      antigen (CEA) level (<5 MUg/L), tumor grade II, and with adjuvant therapy. High
      preoperative monocyte count is independently predictive of worse survival of
      pathological T3N0M0 rectal cancer patients without neoadjuvant chemoradiotherapy.
      Postoperative adjuvant therapy might be considered for patients with high
      monocyte count.

PMID- 25994572
TI  - Interleukin 27 -964A > G genetic polymorphism and serum IL-27p28 levels in
      Chinese patients with papillary thyroid cancer.
AB  - The aim of this study was to investigate the association between a potentially
      functional polymorphism (rs153109, -964A > G) in the promoter region of
      interleukin-27 (IL-27) gene and the risk of papillary thyroid cancer (PTC) in a
      Chinese population. Genotype of IL-27 -964A > G polymorphism was determined using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. Serum IL-27p28 levels were determined using enzyme-linked immunosorbent
      assay (ELISA). No significant difference was noticed in IL-27 -964A > G
      polymorphism between PTC patients and healthy controls in the overall analysis.
      However, analysis of clinical features showed that PTC patients carrying the GG
      genotype or G allele had significantly decreased risks for developing lymph node
      metastasis compared with those carrying the AA genotype or A allele (GG vs. AA:
      OR = 0.38, 95 % CI, 0.20-0.72; G vs. A: OR = 0.63, 95 % CI, 0.44-0.86).
      Furthermore, ELISA results demonstrated that serum IL-27p28 levels were
      significantly decreased in PTC patients compared with those in controls (P <
      0.05). Serum IL-27p28 levels in healthy controls with the GG genotype were
      significantly high compared with those carrying AA genotype or the AG genotype (P
      < 0.05). In conclusion, our results suggest that IL-27 -964A > G polymorphism may
      be associated with the decreased risk for lymph node metastasis of PTC.

PMID- 25994573
TI  - Potential clinical relevance of uPA and PAI-1 levels in node-negative,
      postmenopausal breast cancer patients bearing histological grade II tumors with
      ER/PR expression, during an early follow-up.
AB  - We evaluated urokinase-type plasminogen activator (uPA) and plasminogen activator
      inhibitor-1 (PAI-1) prognostic value in postmenopausal, node-negative breast
      cancer patients bearing tumors with estrogen receptor (ER)/progesterone receptor
      (PR) expression, treated with locoregional therapy alone, within an early follow
      up. We focused our analysis on tumors of histological grade II in order to
      improve its prognostic value and, consequently, to improve a decision-making
      process. The cytosol extracts of 73 tumor samples were used for assessing several
      biomarkers. ER and PR levels were measured by classical biochemical method.
      Cathepsin D was assayed by a radiometric immunoassay while both uPA and PAI-1
      level determinations were performed by enzyme-linked immunosorbent assays. HER-2
      gene amplification was determined by chromogenic in situ hybridization (CISH) in
      primary tumor tissue. Patients bearing tumors smaller than or equal to 2 cm (pT1)
      or those with low PAI-1 levels (PAI-1 < 6.35 pg/mg) showed favorable outcome
      compared to patients bearing tumors greater than 2 cm (pT2,3) or those with high
      PAI-1 levels, respectively. Analyses of 4 phenotypes, defined by tumor size and
      PAI-1 status, revealed that patients bearing either pT1 tumors, irrespective of
      PAI-1 levels, or pT2,3 tumors with low PAI-1 levels, had similar disease-free
      interval probabilities and showed favorable outcome compared to those bearing
      pT2,3 tumors with high PAI-1 levels. Our findings suggest that tumor size and PAI
      1, used in combination as phenotypes are not only prognostic but might also be
      predictive in node-negative, postmenopausal breast cancer patients bearing
      histological grade II tumors with ER/PR expression, during an early follow-up
      period.

PMID- 25994574
TI  - Aminocatalysis-Mediated on-Resin Ugi Reactions: Application in the Solid-Phase
      Synthesis of N-Substituted and Tetrazolo Lipopeptides and Peptidosteroids.
AB  - A new solid-phase protocol for the synthesis of N-substituted and tetrazolo
      peptides is described. The strategy relies on the combination of aminocatalysis
      mediated on-resin Ugi reactions and peptide couplings for the N-alkylation of
      peptides at selected sites, including the N-terminal double lipidation, the
      simultaneous lipidation/biotinylation, and the steroid/lipid conjugation via
      tetrazole ring formation. The solid-phase Ugi four-component reactions were
      enabled by on-resin transimination steps prior to addition of the acid and
      isocyanide components. The strategy proved to be suitable for the feasible
      incorporation of complex N-substituents at both termini and at internal
      positions, which is not easily achievable by other solid-phase methods. 

PMID- 25994575
TI  - Xylose fermentation by Saccharomyces cerevisiae using endogenous xylose
      assimilating genes.
AB  - OBJECTIVES: To genetically engineer Saccharomyces cerevisiae for improved ethanol
      productivity from glucose/xylose mixtures. RESULTS: An endogenous gene cassette
      composed of aldose reductase (GRE3), sorbitol dehydrogenase (SOR1) and xylulose
      kinase (XKS1) with a PGK1 promoter and a terminator was introduced into two S.
      cerevisiae strains, a laboratory strain (CEN.PK2-1C) and an industrial strain
      (Kyokai No. 7). The engineered Kyokai No. 7 strain (K7-XYL) exhibited a higher
      sugar consumption rate (1.03 g l(-1) h(-1)) and ethanol yield (63.8 %) from a
      glucose and xylose mixture compared to the engineered CEN.PK2-1C strain.
      Furthermore, K7-XYL produced a larger amount of ethanol (39.6 g l(-1)) compared
      to K7-SsXYL (32 g l(-1)) with integrated xylose reductase and xylitol
      dehydrogenase from a xylose-assimilating yeast Scheffersomyces stipitis instead
      of GRE3 and SOR1. CONCLUSION: The created S. cerevisiae strain showed sufficient
      xylose-fermenting ability to be used for efficient ethanol production from
      glucose/xylose.

PMID- 25994576
TI  - Production of Delta9-tetrahydrocannabinolic acid from cannabigerolic acid by
      whole cells of Pichia (Komagataella) pastoris expressing Delta9
      tetrahydrocannabinolic acid synthase from Cannabis sativa L.
AB  - OBJECTIVE: The Delta9-tetrahydrocannabinolic acid synthase (THCAS) from Cannabis
      sativa was expressed intracellularly in different organisms to investigate the
      potential of a biotechnological production of Delta9-tetrahydrocannabinolic acid
      (THCA) using whole cells. RESULTS: Functional expression of THCAS was obtained in
      Saccharomyces cerevisiae and Pichia (Komagataella) pastoris using a signal
      peptide from the vacuolar protease, proteinase A. No functional expression was
      achieved in Escherichia coli. The highest volumetric activities obtained were 98
      pkat ml(-1) (intracellular) and 44 pkat ml(-1) (extracellular) after 192 h of
      cultivation at 15  degrees C using P. pastoris cells. Low solubility of CBGA
      prevents the THCAS application in aqueous cell-free systems, thus whole cells
      were used for a bioconversion of cannabigerolic acid (CBGA) to THCA. Finally, 1
      mM (0.36 g THCA l(-1)) THCA could be produced by 10.5 gCDW l(-1) before enzyme
      activity was lost. CONCLUSION: Whole cells of P. pastoris offer the capability of
      synthesizing pharmaceutical THCA production.

PMID- 25994577
TI  - De novo assembly and characterization of the skeletal muscle transcriptome of
      sheep using Illumina paired-end sequencing.
AB  - OBJECTIVE: In order to enrich the ovine genome and provide a basis for future
      molecular genetics and functional genomics analyses in sheep, we used de novo
      assembly to establish transcriptomes of skeletal muscle tissues of Dorper and
      Small-tailed Han sheep. RESULTS: A total of 103,058,824 clean Illumina paired-end
      sequencing reads from the two libraries were assembled into 145,524 unigenes in a
      de novo project. There were 5718 unigenes showing differential expression between
      the two transcriptomes, and 7437 coding SSRs were exploited. After further
      assembly, we identified a total of 70,348 all-unigenes with an average length of
      863 bp; 35,201 of these all-unigenes could be annotated in the Nr database, and
      12,219 were found in the clusters of orthologous groups database. Gene ontology
      searches indicated cell and binding as the main terms. Among 258 Kyoto
      Encyclopedia of Genes and Genomes database pathways, protein and amino acid
      metabolism pathways were the most commonly identified. CONCLUSION: We analyzed
      the ovine muscle transcriptome using high-throughput sequencing technology. Many
      unigenes were assembled and numerous molecular markers and differential expressed
      unigenes were identified.

PMID- 25994578
TI  - Luciferase expression is driven by the promoter of fibroblast activation protein
      alpha in murine pulmonary fibrosis.
AB  - OBJECTIVES: We used optical imaging of live animals and transgenic technology to
      develop a pulmonary fibrosis model in mice that can non-invasively and in real
      time trace the pulmonary fibrosis process. RESULTS: Fibroblast activation protein
      alpha (FAPalpha) is selectively expressed in fibrotic foci of human pulmonary
      fibrosis. It is not expressed in normal tissue. We confirmed that FAPalpha is
      upregulated in fibroblasts of murine pulmonary fibrosis. Moreover, TGF-beta1, a
      central pathological mediator of fibrotic diseases, could promote FAPalpha
      expression in mouse embryonic fibroblasts. Luciferase reporter assays showed that
      5.4 kb FAPalpha promoter response activities to TGF-beta1 was stronger than of
      the 2.1 kb promoter. We generated a transgenic mouse line expressing firefly
      luciferase under the control of the 5.4 kb FAPalpha gene promoter (FAPalpha-p
      luc). After experimentally inducing murine pulmonary fibrosis, there luminescence
      appeared in the chests and excised lungs of FAPalpha-p-luc mice. The intensity of
      luminescence became stronger with the exacerbation of pulmonary fibrosis.
      CONCLUSION: Fluorescence intensity reflects the degree of pulmonary fibrosis in
      FAPalpha-p-luc mice. and this mouse model may be used to investigate molecular
      mechanisms and drug screening of pulmonary fibrosis.

PMID- 25994579
TI  - Enhanced production of porcine circovirus type 2 (PCV2) virus-like particles in
      Sf9 cells by translational enhancers.
AB  - OBJECTIVE: To investigate the effect of three translational enhancers for
      enhancing transgene expression in baculovirus expression vector system using GFP
      as a reporter gene and selected translational enhancers to increase porcine
      circovirus type 2 (PCV2) VLPs production. RESULTS: P10UTR (the 3'-untranslated
      region from the baculovirus p10 gene), Syn21 (a synthetic AT-rich 21-bp sequence)
      and P10UTR/Syn21 increased the GFP yield by 1.4-, 4- and 4.8-fold, respectively.
      While IVS (intron from Drosophila myosin heavy chain gene) decreased the GFP
      yield by 65%. Moreover, the synergy of P10UTR/Syn21 increased the yield of PCV2
      VLPs by 4.1 fold (45 MUg/10(6) cells) compared with standard baculovirus vector.
      CONCLUSION: The synergy of P10UTR/Syn21 is a potential strategy to improve the
      recombinant vaccine production besides PCV2 VLPs in BEVS.

PMID- 25994580
TI  - Direct cloning, expression of a thermostable xylanase gene from the metagenomic
      DNA of cow dung compost and enzymatic production of xylooligosaccharides from
      corncob.
AB  - OBJECTIVES: To acquire a thermostable xylanase, that is suitable for
      xylooligosaccharide production from pretreated corncobs, the metagenomic method
      was used to obtain the gene from an uncultured environmental microorganism.
      RESULTS: A thermostable xylanase-encoding gene (xyn10CD18) was cloned directly
      from the metagenomic DNA of cow dung compost. When xyn10CD18 was expressed in
      Bacillus megaterium MS941, extracellular xylansae activity at 106 IU/ml was
      achieved. The purified recombinant Xyn10CD18 was optimally active at pH 7 and 75 
      degrees C as measured over 10 min. It retained over 55% of its initial activity
      at 70  degrees C and pH 7 after 24 h. Its action on birchwood xylan for 18 h
      liberated xylooligosaccharides with 2 degrees -4 degrees  of polymerization, with
      xylobiose and xylotetraose as the main products. When pretreated corncobs were
      hydrolyzed by Xyn10CD18 for 18 h, the xylooligosaccharides (DP 2-4) products
      increased to 80% and the xylose was just increased by 3%. CONCLUSION: Xyn10CD18
      is a thermostable endoxylanase and is a promising candidate for biomass
      conversion and xylooligosaccharide production.

PMID- 25994581
TI  - Development of a new co-culture system, the "separable-close co-culture system,"
      to enhance stem-cell-to-chondrocyte differentiation.
AB  - OBJECTIVE: To develop a new co-culture system, the separable-close co-culture
      system, to replace the indirect co-culture system which analyzes cellular
      interactions between two groups of cells with each type being cultured separately
      and also the direct co-culture system where the two cell types are cultured
      together. RESULTS: The new system not only achieved effective cellular
      interactions but also allowed the effect that one group of cells has on another
      group of cells to be evaluated. We performed co-culturing of human bone marrow
      mesenchymal stem cells and human articular chondrocytes using the new system. The
      new system made it possible to assess separately the effects of one group of
      cells on the other cell type, as in the indirect co-culture system. Furthermore,
      the new system rivaled or surpassed other co-culture systems in terms of the
      chondrogenic gene expression. CONCLUSION: The new co-culture system is effective
      in terms of assessing gene expression in two cell types.

PMID- 25994582
TI  - Production of rhamnolipids by Pseudomonas aeruginosa is inhibited by H2S but
      resumes in a co-culture with P. stutzeri: applications for microbial enhanced oil
      recovery.
AB  - OBJECTIVES: Sulfate-reducing bacteria and H2S exist widely in oil production
      systems, and in situ production of rhamnolipids is promising for microbial
      enhanced oil recovery (MEOR). However, information of the effect of S(2-) on
      rhamnolipids production is scarce. RESULTS: Two facultative anaerobic
      rhamnolipids-producing bacterial strains, Pseudomonas aeruginosa SG and WJ-1,
      were used. Above 10 mg S(2-)/l, both cell growth and rhamnolipids production were
      inhibited. A large inoculum (9%, v/v) failed to completely relieve the inhibitory
      effect of 10 mg S(2-)/l. Below 30 mg S(2-)/l, both strains resumed rhamnolipid
      production through co-culturing with the denitrifying and sulphide-removing
      strain Pseudomonas stutzeri DQ1. CONCLUSIONS: H2S has a direct but reversible
      inhibitory effect on rhamnolipids production. Control of H2S in oilfields is
      indispensable to MEOR, and the co-culture method is effective in restoring
      rhamnolipid production in presence of S(2-).

PMID- 25994583
TI  - New dioxygenase from metagenomic library from Brazilian soil: insights into
      antibiotic resistance and bioremediation.
AB  - OBJECTIVES: Putative new dioxygenases were identified in a metagenomic beta
      lactam-resistance screening and, given their key role on aromatic metabolism, we
      raise the hypothesis that these enzymes maybe concomitantly related to antibiotic
      resistance and aromatic degradation. RESULTS: ORFs of three putative dioxygenases
      were isolated from resistant metagenomic clones. One of them, CRB2(1), was
      subcloned into pET24a expression vector and subjected to downstream phenotypic
      and bioinformatics analyses that demonstrated the "dual effect" of our
      metagenomic dioxygenase, on antibiotic and aromatic resistance. Furthermore,
      initial characterization assays strongly suggests that CRB2(1) open-reading frame
      is an extradiol-dioxygenase, most probably a bicupin domain gentisate 1,2
      dioxygenase. This observation is, to our knowledge, the first description of a
      metagenomic dioxygenase and its action on beta-lactam resistance. CONCLUSION:
      Unraveling the diversity of antibiotic resistance elements on the environment
      could not only identify new genes and mechanisms in which bacteria can resist to
      antibiotics, but also contribute to biotechnology processes, such as in
      bioremediation.

PMID- 25994584
TI  - Bioconversion of vitamin D3 to calcifediol by using resting cells of
      Pseudonocardia sp.
AB  - OBJECTIVES: Resting cells of Pseudonocardia sp. KCTC 1029BP were used for the
      bioconversion of vitamin D3 to calcifediol which is widely used to treat
      osteomalacia and is industrially produced by chemical synthesis. RESULTS: To
      obtain the maximum bioconversion yield of calcifediol by the microbial conversion
      of vitamin D3, a two-step optimization process was used, including the Plackett
      Burman and the central composite designs. Six variables, namely agitation speed,
      aeration rate, resting cell concentration, vitamin D3 concentration, temperature,
      and pH, were monitored. Of these, aeration rate, resting cell concentration, and
      temperature were selected as key variables for calcifediol production and were
      optimized using the central composite design. Optimal bioconversion conditions
      obtained were as follows: aeration rate of 0.2 vvm, resting cell concentration of
      4.7% w/v, and temperature of 33  degrees C. CONCLUSION: Using the optimal
      conditions, 356 mg calcifediol l(-1) was obtained with a bioconversion yield of
      59.4% in a 75 l fermentor. These are the highest values reported to date.

PMID- 25994585
TI  - The water footprint of biofilm cultivation of Haematococcus pluvialis is greatly
      decreased by using sealed narrow chambers combined with slow aeration rate.
AB  - OBJECTIVE: Biofilm cultivation of microalgae has great potential in many
      applications. However, the water footprint for this method has not been well
      assessed. This issue was explored with the microalga Haematococcus pluvialis.
      RESULTS: Only 1.25 l water is sufficient to support 1 m(2) biofilm cultivation
      surface. To produce 1 kg Haematococcus biomass and astaxanthin, the water
      footprint could be as low as 35.7 and 1440 l, respectively, by sealing the
      biofilm in a narrow chamber and supplying the proper amount of nutrients if the
      evaporation water loss was not considered. However, when loss of water by
      evaporation was considered, the water footprint was as low as 66.9 and 2700 l,
      respectively, if the chamber was aerated with CO2 at 0.014 vvm. These water
      footprint values are much lower than values obtained in other research work.
      CONCLUSIONS: The water footprint of biofilm microalgal cultivation can be
      potentially reduced by more than 90% if the biofilm is sealed in a narrow chamber
      and supplied with a slow aeration of CO2 as carbon source.

PMID- 25994586
TI  - Quantifying solvated electrons' delocalization.
AB  - Delocalized, solvated electrons are a topic of much recent interest. We apply the
      electron delocalization range EDR(r;u) (J. Chem. Phys., 2014, 141, 144104) to
      quantify the extent to which a solvated electron at point r in a calculated
      wavefunction delocalizes over distance u. Calculations on electrons in one
      dimensional model cavities illustrate fundamental properties of the EDR. Mean
      field calculations on hydrated electrons (H2O)n(-) show that the density-matrix
      based EDR reproduces existing molecular-orbital-based measures of delocalization.
      Correlated calculations on hydrated electrons and electrons in lithium-ammonia
      clusters illustrates how electron correlation tends to move surface- and cavity
      bound electrons onto the cluster or cavity surface. Applications to multiple
      solvated electrons in lithium-ammonia clusters provide a novel perspective on the
      interplay of delocalization and strong correlation central to lithium-ammonia
      solutions' concentration-dependent insulator-to-metal transition. The results
      motivate continued application of the EDR to simulations of delocalized
      electrons.

PMID- 25994587
TI  - Targeted Overexpression of Astrocytic Endothelin-1 Attenuates Neuropathic Pain by
      Upregulating Spinal Excitatory Amino Acid Transporter-2.
AB  - We previously demonstrated that endogenous endothelin-1 (ET-1) inhibits
      pathological pain in a transgenic mouse model with astrocyte-specific ET-1
      overexpression (GET-1 mice); however, the underlying mechanism is unclear. ET-1
      regulates excitatory amino acid transporter-2 (EAAT-2), a predominant subtype of
      glutamate transporters that plays critical role in pain modulation in spinal
      astrocytes. We hypothesized that astrocytic ET-1 overexpression alleviates
      neuropathic pain through modulating EAAT-2. GET-1 or nontransgenic (NTg) mice
      either received sham operation or sciatic nerve ligation (SNL) with or without
      ceftriaxone (CEF, an EAAT-2 inducer, for 4 days before termination). In GET-1
      mice, mRNA and protein expressions of EAAT-2, but not EAAT-1, were upregulated
      associated with reduced SNL-induced neuropathic pain. Despite that SNL induced a
      significant reduction of EAAT-2 mRNA expression in both genotypes of mice, post
      SNL EAAT-2 mRNA expression was higher in GET-1 mice than that in NTg mice. EAAT-2
      induction by CEF reduced SNL-induced neuropathic pain in both NTg and GET-1 mice.
      In cultured rat astrocytic cell line, overexpression of ET-1 mRNA expression also
      elevated EAAT-2 mRNA expression, which was reversed by ET receptor antagonists.
      In conclusion, overexpressed astrocytic ET-1 suppressed neuropathic pain by
      upregulating spinal EAAT-2 expression via ET receptors. 

PMID- 25994588
TI  - Tick-borne diseases of bovines in Pakistan: major scope for future research and
      improved control.
AB  - Ticks and tick-borne diseases (TBDs) affect the productivity of bovines in
      tropical and subtropical regions of the world, leading to a significant adverse
      impact on the livelihoods of resource-poor farming communities. Globally, four
      main TBDs, namely anaplasmosis, babesiosis, theileriosis, and cowdriosis
      (heartwater) affect bovines, and the former three are of major economic
      importance in bovines in Pakistan. Given that the livestock sector has become an
      integral part of Pakistan's economy and a large number of dairy cattle are being
      imported into the country, in order to meet an increasing demand of milk and milk
      products, it is timely to review current status of bovine TBDs in Pakistan and to
      identify gaps in the knowledge of TBDs and their control. Although there has been
      a recent increase in the number of studies of TBDs in this country, information
      on their prevalence, distribution, tick vectors, and control is limited. This
      article provides a brief background on key bovine TBDs and ticks and reviews the
      current status of bovine TBDs in Pakistan to identify gaps in knowledge and
      understanding of these diseases, propose areas for future research and draw
      attention to the need for improved tools for the diagnosis and control of TBDs in
      this country. 

PMID- 25994589
TI  - Corruption and population health outcomes: an analysis of data from 133 countries
      using structural equation modeling.
AB  - OBJECTIVES: The current study aims to develop a theoretical framework for
      understanding the antecedents of corruption and the effects of corruption on
      various health indicators. METHODS: Using structural equation models, we analyzed
      a multinational dataset of 133 countries that included three main groups of
      variables--antecedents of corruption, corruption measures, and health indicators.
      RESULTS: Controlling for various factors, our results suggest that corruption
      rises as GDP per capita falls and as the regime becomes more autocratic. Higher
      corruption is associated with lower levels of health expenditure as a percentage
      of GDP per capita, and with poorer health outcomes. Countries with higher GDP per
      capita and better education for women have better health outcomes regardless of
      health expenditures and regime type. CONCLUSIONS: Our results suggest that there
      is no direct relationship between health expenditures and health outcomes after
      controlling for the other factors in the model. Our study enhances our
      understanding of the conceptual and theoretical links between corruption and
      health outcomes in a population, including factors that may mediate how
      corruption can affect health outcomes.

PMID- 25994590
TI  - Educational expectations and adolescent health behaviour: an evolutionary
      approach.
AB  - OBJECTIVES: Previous research finds adolescents expecting to attend university
      are more likely to demonstrate health-promoting behaviour than those not
      expecting university attendance. This suggests public health improvements may be
      achievable by encouraging adolescents to adopt academic goals. We investigate
      confounders of this putative relationship, focusing on those identified by
      evolutionary theory. METHODS: Multi-level logistic regression was used to analyse
      the 2010 Scottish Health Behaviour in School-aged Children survey (n = 1834).
      RESULTS: Adolescents anticipating university attendance exhibited higher levels
      of engagement in health-protective behaviours (fruit and vegetable consumption,
      exercise and tooth brushing) and were more likely to avoid health-damaging
      behaviours (crisps, soft drink and alcohol consumption, tobacco and cannabis use,
      fighting and intercourse). These relationships persisted when controlling
      indicators of life history trajectory (pubertal timing, socioeconomic status and
      father absence). Pupil level: gender, age, perceived academic achievement and
      peer/family communication and school level: university expectations, affluence,
      leavers' destinations, exam performance and school climate were also adjusted.
      CONCLUSIONS: Encouraging adolescents to consider an academic future may achieve
      public health benefits, despite social factors that might otherwise precipitate
      poor health via an accelerated life history trajectory.

PMID- 25994591
TI  - Impact of exercise on diurnal and nocturnal markers of glycaemic variability and
      oxidative stress in obese individuals with type 2 diabetes or impaired glucose
      tolerance.
AB  - OBJECTIVE: We measured the effects of a single bout of exercise on diurnal and
      nocturnal oxidative stress and glycaemic variability in obese subjects with type
      2 diabetes mellitus or impaired glucose tolerance versus obese healthy controls.
      METHODS: Subjects (in random order) performed either a single 30-min bout of
      moderate-intensity exercise or remained sedentary for 30 min at two separate
      visits. To quantify glycaemic variability, standard deviation of glucose
      (measured by continuous glucose monitoring system) and continuous overlapping net
      glycaemic action of 1-h intervals (CONGA-1) were calculated for three 12-h
      intervals during each visit. Oxidative stress was measured by 15-isoprostane
      F(2t) levels in urine collections for matching 12-h intervals. RESULTS: Exercise
      reduced daytime glycaemic variability (DeltaCONGA-1 = -12.62 +/- 5.31 mg/dL, p =
      0.04) and urinary isoprostanes (DeltaCONGA-1 = -0.26 +/- 0.12 ng/mg, p = 0.04) in
      the type 2 diabetes mellitus/impaired glucose tolerance group. Daytime exercise
      induced change in urinary 15-isoprostane F(2t) was significantly correlated with
      both daytime standard deviation (r = 0.68, p = 0.03) and with subsequent
      overnight standard deviation (r = 0.73, p = 0.027) in the type 2 diabetes
      mellitus/impaired glucose tolerance group. CONCLUSION: Exercise significantly
      impacts the relationship between diurnal oxidative stress and nocturnal glycaemic
      variability in individuals with type 2 diabetes mellitus/impaired glucose
      tolerance.

PMID- 25994592
TI  - Chirality of Single-Handed Twisted Titania Tubular Nanoribbons Prepared Through
      Sol-gel Transcription.
AB  - Single-handed twisted titania tubular nanoribbons were prepared through sol-gel
      transcription using a pair of enantiomers. Handedness was controlled by that of
      the template. The obtained samples were characterized using field-emission
      electron microscopy, transmission electron microscopy, diffuse reflectance
      circular dichroism (DRCD), and X-ray diffraction. The DRCD spectra indicated that
      the titania nanotubes exhibit optical activity. Although the tubular structure
      was destroyed after being calcined at 700  degrees C for 2.0 h, DRCD signals were
      still identified. However, the DRCD signals disappeared after being calcined at
      1000  degrees C for 2.0 h. The optical activity of titania was proposed to be due
      to chiral defects. Previous results showed that straight titania tubes could be
      used as asymmetric autocatalysts, indicating that titania exhibit chirality at
      the angstrom level. Herein, it was found that they also exhibit DRCD signals,
      indicating that there are no obvious relationships between morphology at the nano
      level and chirality at the angstrom level. The nanotube chirality should
      originate from the chiral defects on the nanotube inner surface. The Fourier
      transform infrared spectra indicated that the chirality of the titania was
      transferred from the gelators through the hydrogen bonding between N-H and Ti-OH.

PMID- 25994593
TI  - Waist circumference to height ratio and left ventricular mass in children and
      adolescents.
AB  - OBJECTIVES: Waist circumference to height ratio, a measure of central obesity, is
      a better predictor of cardiovascular risk than body mass index in the paediatric
      population. Increased left ventricular mass secondary to obesity and hypertension
      increases the risk for death and cardiovascular disease in adults. Similar data
      on left ventricular mass are lacking among young patients with central obesity,
      as defined by waist circumference/height. The present study evaluates left
      ventricular mass in young patients with central obesity as defined by waist
      circumference/height. METHODS: A total of 156 patients, 2- to 20-years old,
      without evidence of structural heart disease were studied. As the left
      ventricular mass is related to age and gender, 52 patients with central obesity -
      waist circumference/height ?0.55 - were randomly matched for age and gender with
      52 patients at risk for central obesity - waist circumference/height ?0.5 to
      <0.55 - and 52 patients with no central obesity - waist circumference/height
      <0.5. The left ventricular mass parameters measured by echocardiography were
      compared across the three groups. RESULTS: Patients with central obesity had
      significantly (p<0.05) increased Z scores for left ventricular mass, left
      ventricular mass/height2.7, and left ventricular mass/height1.7 compared with
      patients at risk for central obesity and patients with no central obesity. Z
      scores for left ventricular mass were higher among patients at risk for central
      obesity compared with patients with no central obesity. CONCLUSIONS: Left
      ventricular mass data of the present study support maintaining an ideal waist
      circumference/height <0.5. Aggressive efforts to identify and manage patients
      with central obesity are warranted.

PMID- 25994594
TI  - Unexpected behavior of irradiated spider silk links conformational freedom to
      mechanical performance.
AB  - Silk fibers from Argiope trifasciata and Nephila inaurata orb-web weaving spiders
      were UV irradiated to modify the molecular weight of the constituent proteins.
      Fibers were characterized either as forcibly silked or after being subjected to
      maximum supercontraction. The effect of irradiation on supercontraction was also
      studied, both in terms of the percentage of supercontraction and the tensile
      properties exhibited by irradiated and subsequently supercontracted fibers. The
      effects of UV exposure at the molecular level were assessed by polyacrylamide gel
      electrophoresis and mass spectrometry. It is shown that UV-irradiated fibers show
      a steady decrease in their main tensile parameters, most notably, tensile
      strength and strain. The combination of the mechanical and biochemical data
      suggests that the restricted conformational freedom of the proteins after UV
      irradiation is critical in the reduction of these properties. Consequently, an
      adequate topological organization of the protein chains emerges as a critical
      design principle in the performance of spider silk. 

PMID- 25994595
TI  - Generation and characterization of osteochondral grafts with human nasal
      chondrocytes.
AB  - We investigated whether nasal chondrocytes (NC) can be used to generate composite
      constructs with properties necessary for the repair of osteochondral (OC)
      lesions, namely maturation, integration and capacity to recover from inflammatory
      burst. OC grafts were fabricated by combining engineered cartilage tissues
      (generated by culturing NC or articular chondrocytes - AC - onto Chondro-Gide(r)
      matrices) with devitalized spongiosa cylinders (Tutobone(r)). OC tissues were
      then exposed to IL-1beta for three days and cultured for additional 2 weeks in
      the absence of IL-1beta. Cartilage maturation extent was assessed (immune)
      histologically, biochemically and by delayed gadolinium-enhanced magnetic
      resonance imaging of cartilage (dGEMRIC) while cartilage/bone integration was
      assessed using a peel-off mechanical test. The use of NC as compared to AC
      allowed for more efficient cartilage matrix accumulation and superior integration
      of the cartilage/bone layers. dGEMRIC and biochemical analyzes of the OC
      constructs showed a reduced glycosaminoglycan (GAG) contents upon IL-1beta
      administration. Cartilaginous matrix contents and integration forces returned to
      baseline up on withdrawal of IL-1beta. By having a cartilage layer well developed
      and strongly integrated to the subchondral layer, OC tissues generated with NC
      may successfully engraft in an inflammatory post-surgery joint environment.

PMID- 25994596
TI  - Conformational ensembles and sampled energy landscapes: Analysis and comparison.
AB  - We present novel algorithms and software addressing four core problems in
      computational structural biology, namely analyzing a conformational ensemble,
      comparing two conformational ensembles, analyzing a sampled energy landscape, and
      comparing two sampled energy landscapes. Using recent developments in
      computational topology, graph theory, and combinatorial optimization, we make two
      notable contributions. First, we present a generic algorithm analyzing height
      fields. We then use this algorithm to perform density-based clustering of
      conformations, and to analyze a sampled energy landscape in terms of basins and
      transitions between them. In both cases, topological persistence is used to
      manage (geometric) frustration. Second, we introduce two algorithms to compare
      transition graphs. The first is the classical earth mover distance metric which
      depends only on local minimum energy configurations along with their statistical
      weights, while the second incorporates topological constraints inherent to
      conformational transitions. Illustrations are provided on a simplified protein
      model (BLN69), whose frustrated potential energy landscape has been thoroughly
      studied. The software implementing our tools is also made available, and should
      prove valuable wherever conformational ensembles and energy landscapes are used.

PMID- 25994597
TI  - MOLSIM: A modular molecular simulation software.
AB  - The modular software MOLSIM for all-atom molecular and coarse-grained simulations
      is presented with focus on the underlying concepts used. The software possesses
      four unique features: (1) it is an integrated software for molecular dynamic,
      Monte Carlo, and Brownian dynamics simulations; (2) simulated objects are
      constructed in a hierarchical fashion representing atoms, rigid molecules and
      colloids, flexible chains, hierarchical polymers, and cross-linked networks; (3)
      long-range interactions involving charges, dipoles and/or anisotropic dipole
      polarizabilities are handled either with the standard Ewald sum, the smooth
      particle mesh Ewald sum, or the reaction-field technique; (4) statistical
      uncertainties are provided for all calculated observables. In addition, MOLSIM
      supports various statistical ensembles, and several types of simulation cells and
      boundary conditions are available. Intermolecular interactions comprise tabulated
      pairwise potentials for speed and uniformity and many-body interactions involve
      anisotropic polarizabilities. Intramolecular interactions include bond, angle,
      and crosslink potentials. A very large set of analyses of static and dynamic
      properties is provided. The capability of MOLSIM can be extended by user
      providing routines controlling, for example, start conditions, intermolecular
      potentials, and analyses. An extensive set of case studies in the field of soft
      matter is presented covering colloids, polymers, and crosslinked networks.

PMID- 25994600
TI  - CBCT quantitative evaluation of mandibular lingual concavities in dental implant
      patients.
AB  - PURPOSE: The purpose of this study was to evaluate the prevalence of mandibular
      lingual concavities and to measure them using CBCT (Cone-Beam Computerized
      Tomography). METHODS: In this study, CBCT scans of 200 patients requiring dental
      implants were assessed for lingual concavities. Reconstructed CBCT images were
      transferred as DICOM files to the 3D DOCTOR software program, and metric,
      volumetric, and surface area measurements were obtained. Two-way mixed ANOVA was
      used to model side (left/right, anterior), measurement type, and gender with side
      and type taken as within-subject variables, gender as between-subject variables,
      and age as a covariate. A comparison between the dentate and edentulous groups in
      the samples with lingual concavities was performed using an unpaired Student's t
      test. RESULTS: Submandibular concavity mean depth and volume were found to be 2.4
      mm and 130.7 mm(3), whereas mean depth and volume of sublingual concavities were
      found to be 1.3 mm and 26.5 mm(3). Significant inverse ratios were found between
      age and volume and between age and surface area (p < 0.05). All measurements were
      higher in males than females, but the differences were not statistically
      significant. The differences between the presence of concavity (sublingual,
      right, and left submandibular) and dental status (dentate/edentulous) were
      statistically insignificant (p > 0.05). CONCLUSION: Mandibular lingual concavity
      dimensions were found to vary by age, location, and the presence/absence of
      teeth. Third party software can be used to generate 3-dimensional models that
      provide useful information about shape, size, and location of sublingual and
      submandibular concavities prior to implant placement.

PMID- 25994601
TI  - Strategy for selecting nanotechnology carriers to overcome immunological and
      hematological toxicities challenging clinical translation of nucleic acid-based
      therapeutics.
AB  - INTRODUCTION: Clinical translation of nucleic acid-based therapeutics (NATs) is
      hampered by assorted challenges in immunotoxicity, hematotoxicity,
      pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are
      being considered to help address some of these challenges due to the
      nanoparticles' ability to change drug biodistribution, stability, circulation
      half-life, route of administration and dosage. Addressing toxicology and
      pharmacology concerns by various means including NATs reformulation using
      nanotechnology-based carriers has been reviewed before. However, little attention
      was given to the immunological and hematological issues associated with
      nanotechnology reformulation. AREAS COVERED: This review focuses on application
      of nanotechnology carriers for delivery of various types of NATs, and how
      reformulation using nanoparticles affects immunological and hematological
      toxicities of this promising class of therapeutic agents. EXPERT OPINION: NATs
      share several immunological and hematological toxicities with common
      nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable
      immunological and hematological effects of NATs by a nanocarrier, it is critical
      to consider the immunological compatibility of the nanotechnology platform and
      its components. Since receptors sensing nucleic acids are located essentially in
      all cellular compartments, a strategy for developing a nanoformulation with
      reduced immunotoxicity should first focus on precise delivery to the target
      site/cells and then on optimizing intracellular distribution.

PMID- 25994602
TI  - Comorbid diseases of IgG4-related sialadenitis in the head and neck region.
AB  - OBJECTIVES/HYPOTHESIS: To further recognize the comorbid diseases of
      immunoglobulin G4-related sialadenitis (IgG4-RS) in the head and neck region and
      to observe the response of these conditions to immunomodulatory therapy. STUDY
      DESIGN: Retrospective review. METHODS: The symptoms of comorbid diseases and
      medical histories in 51 patients (24 men, 27 women; median age, 55 years)
      diagnosed with IgG4-RS were analyzed. Thirty-six patients received
      immunomodulatory therapy and were followed up for 10.4 +/- 5.9 months. Computed
      tomography (CT) examination was performed before and after therapy. RESULTS:
      Rhinosinusitis occurred in 58.8% patients, and manifested with the symptoms of
      nasal obstruction, nasal xerosis, and hyposmia. In addition, 43.1% patients had
      allergic rhinitis. Lymphadenopathy was identified in 74.5% patients. Lacrimal
      gland swelling occurred in 78.4% patients. Extraocular muscles, otologic organs,
      skin and superficial soft tissue, and cranial nerves were also involved. All of
      the lesions were relieved after immunomodulatory therapy. The Lund-Mackay scores
      decreased (9.6 +/- 5.6 to 1.0 +/- 2.2) according to CT analyses (P < .05). Mean
      CT volumes of the swollen lymph nodes and lacrimal glands decreased from 1.21 +/-
      0.61 cm(3) to 0.59 +/- 0.35 cm(3) and from 2.25 +/- 1.35 cm(3) to 0.70 +/- 0.32
      cm(3), respectively (P < .05) after treatment. CONCLUSIONS: IgG4-RS could
      potentially develop with involvement of ocular adnexa, sinonasal cavities, ears,
      lymph nodes, skin and superficial soft tissue, and cranial nerves in the head and
      neck region. Immunomodulatory therapy could be effective in controlling both the
      comorbid diseases of IgG4-RS and sialadenitis of the major salivary glands. LEVEL
      OF EVIDENCE: 4.

PMID- 25994604
TI  - TLR4 as a possible key regulator of pathological vascular remodeling by Ang II
      receptor activation.

PMID- 25994603
TI  - Comparison of the effects of barnidipine+losartan compared with
      telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in
      patients with hypertension and type 2 diabetes mellitus.
AB  - The aim of this study was to evaluate the effects of barnidipine+losartan
      compared with telmisartan+hydrochlorothiazide on several parameters of insulin
      sensitivity in patients with hypertension and type 2 diabetes mellitus. We
      enrolled 148 normocholesterolemic patients with mild-to-moderate hypertension and
      type 2 diabetes mellitus. Patients were treated with barnidipine, 20 mg day(-1),
      in combination with losartan, 100 mg day(-1), or with
      telmisartan+hydrochlorothiazide, 80/12.5 mg day(-1), for 6 months. We assessed
      blood pressure (BP) on a monthly basis; additionally, blood samples were
      collected to assess, at baseline and after 6 months, the following parameters:
      fasting plasma glucose; glycated hemoglobin; fasting plasma insulin; HOMA index;
      and some adipocytokines, such as adiponectin (ADN), resistin, leptin, visfatin
      and vaspin. Patients were also subjected to an euglycemic hyperinsulinemic clamp
      to assess the M value and glucose infusion rate to ascertain their insulin
      sensitivity. One hundred and forty-one patients completed the study. The BP was
      reduced in both groups, although the reduction was greater with
      barnidipine+losartan (P<0.001 vs. baseline and P<0.01 vs.
      telmisartan+hydrochlorothiazide). Barnidipine+losartan increased the M value and
      glucose infusion rate during the euglycemic hyperinsulinemic clamp (P<0.05 vs.
      baseline and vs. telmisartan+hydrochlorothiazide). With respect to the levels of
      adipocytokines, ADN was increased (P<0.05), and resistin and leptin were reduced
      from baseline with barnidipine+losartan (P<0.05 vs. baseline), but they were not
      reduced with telmisartan+hydrochlorothiazide. Visfatin and vaspin were reduced by
      barnidipine+losartan compared with baseline (P<0.05). The adipocytokine levels
      obtained with barnidipine+losartan were significantly better than those obtained
      with telmisartan+hydrochlorothiazide (P<0.05 for all parameters). In addition to
      providing a greater BP reduction, barnidipine+losartan improved the insulin
      sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, and improved
      some of the adipocytokines related to insulin resistance.

PMID- 25994605
TI  - [Patients with pain in outpatient care. A nationwide cross-sectional survey with
      path model].
AB  - BACKGROUND: There is limited knowledge on the degree of pain and pain-related
      impairments in home care clients. This study was carried out to provide data on
      the prevalence of pain and pain-related impairments in home care patients and to
      investigate the impact on activities of daily living and on classification into
      the three levels of care as defined by the statutory German long-term care
      insurance. MATERIAL AND METHODS: In 2012 a representative cross-sectional
      multicenter study was conducted among clients of 100 German home care services.
      The stepwise sampling procedure included a random selection of 9 home care
      services in each of the 16 federal states and a randomized sampling among the
      clients of the participating home care services. The total sample consisted of
      878 home care clients (inclusion criteria >= 18 years). The subjective pain
      intensity was measured using an 11-step Likert scale ranging from 0 (no pain) to
      10 (most severe pain). Pain-related impairments were rated on a 6-step Likert
      scale (0 = no impairments to 5 = complete impairment) assessing the level of
      independence in household chores, mobility, personal hygiene, dressing and social
      participation. Furthermore, multimorbidity (number of diagnoses) and level of
      care according to the current classification in the German long-term care
      insurance were registered. The predictive significance of latent variables was
      determined by structural equation modelling. RESULTS: Of the subjects surveyed
      68.5 % (n = 672) reported suffering from pain. The average intensity of pain was
      2.9 (standard deviation SD 2.8) and pain-related impairments had the greatest
      effect on mobility (78.2 %). Path analysis revealed that a higher degree of pain
      related impairments (beta = + 0.31) and a higher number of diagnoses (beta = +
      0.19) were associated with classification to higher levels of care as defined in
      the German long-term care insurance. However, stronger pain and higher age were
      related to a classification to a lower level of care (beta = - 0.21). No relevant
      gender differences were identified except for the finding that old age in women
      had no significant effect on the classification to the level of care, whereas in
      men both old age and pain intensity did have an impact. CONCLUSION: Even though
      the majority of home care clients in this representative study suffered from
      pain, the degree of pain intensity only becomes an issue in home care if it
      concurs with impairments in daily living and a corresponding classification to
      higher levels of care dependency. These findings suggest that pain and pain
      management should receive more attention in home care, irrespective of observable
      impairments in daily living. In practice, nurses in home care services should
      regularly assess the level of pain intensity among home care clients and the
      results of these regular pain assessments should be taken into account for the
      identification of individual care needs.

PMID- 25994606
TI  - [Acute pain therapy in German hospitals as competitive factor. Do competition,
      ownership and case severity influence the practice of acute pain therapy?].
AB  - BACKGROUND: Due to the implementation of the diagnosis-related groups (DRG)
      system, the competitive pressure on German hospitals increased. In this context
      it has been shown that acute pain management offers economic benefits for
      hospitals. The aim of this study was to analyze the impact of the competitive
      situation, the ownership and the economic resources required on structures and
      processes for acute pain management. MATERIAL AND METHODS: A standardized
      questionnaire on structures and processes of acute pain management was mailed to
      the 885 directors of German departments of anesthesiology listed as members of
      the German Society of Anesthesiology and Intensive Care Medicine (DGAI, Deutsche
      Gesellschaft fur Anasthesiologie und Intensivmedizin). RESULTS: For most
      hospitals a strong regional competition existed; however, this parameter affected
      neither the implementation of structures nor the recommended treatment processes
      for pain therapy. In contrast, a clear preference for hospitals in private
      ownership to use the benchmarking tool QUIPS (quality improvement in
      postoperative pain therapy) was found. These hospitals also presented information
      on coping with the management of pain in the corporate clinic mission statement
      more often and published information about the quality of acute pain management
      in the quality reports more frequently. No differences were found between
      hospitals with different forms of ownership in the implementation of acute pain
      services, quality circles, expert standard pain management and the implementation
      of recommended processes. Hospitals with a higher case mix index (CMI) had a
      certified acute pain management more often. The corporate mission statement of
      these hospitals also contained information on how to cope with pain, presentation
      of the quality of pain management in the quality report, implementation of
      quality circles and the implementation of the expert standard pain management
      more frequently. There were no differences in the frequency of using the
      benchmarking tool QUIPS or the implementation of recommended treatment processes
      with respect to the CMI. CONCLUSION: In this survey no effect of the competitive
      situation of hospitals on acute pain management could be demonstrated. Private
      ownership and a higher CMI were more often associated with structures of acute
      pain management which were publicly accessible in terms of hospital marketing.

PMID- 25994607
TI  - Identification of sibling species status of Anopheles culicifacies breeding in
      polluted water bodies in Trincomalee district of Sri Lanka.
AB  - BACKGROUND: Anopheles culicifacies s.l., the major vector of malaria in Sri
      Lanka, is known to breed in clean and clear water. However, recent findings have
      confirmed breeding from waste water bodies in urban and semi-urban areas. No
      study has been conducted to identify whether it is vector or non-vector siblings.
      The objective of the study was to identify the sibling species status of An.
      culicifacies s.l. METHODS: Anopheles culicifacies s.l. adult samples (reared from
      larvae) were obtained from the Padavisiripura Entomological team attached to
      Tropical and Environmental Diseases and Health Associates (TEDHA) Malaria
      Elimination Programme in Trincomalee District. The collected mosquito specimens
      were processed for the extraction of genomic DNA individually. The PCR
      amplifications were carried out using different primer combinations for
      differentiating species A from D, species B from C, species B from E, and species
      B, C, and E from each other. The results obtained from the gel electrophoresis
      were compared with the marker and band sizes of 359 bp, 248 bp, 95+248 bp,
      166+359 bp and 178+248 bp were used to compare the sibling species A, B, C, D and
      E, respectively. RESULTS: The molecular biological identification of the field
      caught An. culicifacies s.l. samples observed that only 13.34% (4/30) was
      represented sibling species B. About 86.66% (26/30) of the samples were An.
      culicifacies sibling species E. This study also provided evidence that An.
      culicifacies E was able to breed in a wide range of breeding habitats. This is
      the first time that An. culicifacies E breeding in waste water was confirmed by a
      molecular method. Malaria control programmes in most parts of the country focus
      on rural communities as a result of bio-ecology of mosquitoes. Therefore, unusual
      breeding habitats, such as waste water collections, may mislead the current
      vector controlling programmes. CONCLUSIONS: These results reconfirm that An.
      culicifacies s.l. has adapted to breed in a wide range of water bodies, including
      waste water collections. Since the majority of mosquitoes sampled belong to
      sibling species E, this may adversely affect the current malaria elimination
      programme and new strategies should be adopted to control malaria vectors
      breeding in these unusual breeding habitats in Sri Lanka.

PMID- 25994609
TI  - Life under extreme energy limitation: a synthesis of laboratory- and field-based
      investigations.
AB  - The ability of microorganisms to withstand long periods with extremely low energy
      input has gained increasing scientific attention in recent years. Starvation
      experiments in the laboratory have shown that a phylogenetically wide range of
      microorganisms evolve fitness-enhancing genetic traits within weeks of incubation
      under low-energy stress. Studies on natural environments that are cut off from
      new energy supplies over geologic time scales, such as deeply buried sediments,
      suggest that similar adaptations might mediate survival under energy limitation
      in the environment. Yet, the extent to which laboratory-based evidence of
      starvation survival in pure or mixed cultures can be extrapolated to sustained
      microbial ecosystems in nature remains unclear. In this review, we discuss past
      investigations on microbial energy requirements and adaptations to energy
      limitation, identify gaps in our current knowledge, and outline possible future
      foci of research on life under extreme energy limitation. 

PMID- 25994608
TI  - Structural and functional characterization of a novel scFv anti-HSP60 of
      Strongyloides sp.
AB  - Phage display is a powerful technology that selects specific proteins or peptides
      to a target. We have used Phage Display to select scFv (single-chain variable
      fragment) clones from a combinatorial library against total proteins of
      Strongyloides venezuelensis. After scFv characterization, further analysis
      demonstrated that this recombinant fragment of antibody was able to bind to an S.
      venezuelensis antigenic fraction of ~65 kDa, present in the body periphery and
      digestive system of infective larvae (L3), as demonstrated by immunofluorescence.
      Mass spectrometry results followed by bioinformatics analysis showed that this
      antigenic fraction was a heat shock protein 60 (HSP60) of Strongyloides sp. The
      selected scFv was applied in serodiagnosis by immune complexes detection in serum
      samples from individuals with strongyloidiasis using a sandwich enzyme-linked
      immunosorbent assay (ELISA), showing sensitivity of 97.5% (86.84-99.94),
      specificity of 98.81 (93.54-99.97), positive likelihood ratio of 81.60 and an
      area under the curve of 0.9993 (0.9973-1.000). Our study provided a novel
      monoclonal scFv antibody fragment which specifically bound to HSP60 of
      Strongyloides sp. and was applied in the development of an innovative
      serodiagnosis method for the human strongyloidiasis. 

PMID- 25994610
TI  - Phagocyte subsets and lymphocyte clonal deletion behind ineffective immune
      response to Staphylococcus aureus.
AB  - Lack of known mechanisms of protection against Staphylococcus aureus in humans is
      hindering development of efficacious vaccines. Preclinical as well as clinical
      data suggest that antibodies play an important role against S. aureus. For
      instance, certain hypogammaglobulinaemic patients are at increased risk of
      staphylococcal infections. However, development of effective humoral response may
      be dampened by converging immune-evasion mechanisms of S. aureus. We hypothesize
      that B-cell proliferation induced by staphylococcal protein A (SpA) and
      continuous antigen exposure, without the proper T-cell help and cytokine stimuli,
      leads to antigen-activated B-cell deletion and anergy. Recent findings suggest an
      important role of type I neutrophils (PMN-I) and conventionally activated
      macrophages (M1) against S. aureus, while alternatively activated macrophages
      (M2) favour biofilm persistence and sepsis. In addition, neutrophil-macrophage
      cooperation promotes extravasation and activation of neutrophils as well as
      clearance of bacteria ensnared in neutrophil extracellular traps. Activation of
      these processes is modulated by cytokines and T cells. Indeed, low CD4(+) T-cell
      counts represent an important risk factor for skin infections and bacteraemia in
      patients. Altogether, these observations could lead to the identification of
      predictive correlates of protection and ways for shifting the balance of the
      response to the benefit of the host through vaccination. 

PMID- 25994611
TI  - Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive
      immunity.
AB  - CRISPR-Cas is an RNA-mediated adaptive immune system that defends bacteria and
      archaea against mobile genetic elements. Short mature CRISPR RNAs (crRNAs) are
      key elements in the interference step of the immune pathway. A CRISPR array
      composed of a series of repeats interspaced by spacer sequences acquired from
      invading mobile genomes is transcribed as a precursor crRNA (pre-crRNA) molecule.
      This pre-crRNA undergoes one or two maturation steps to generate the mature
      crRNAs that guide CRISPR-associated (Cas) protein(s) to cognate invading genomes
      for their destruction. Different types of CRISPR-Cas systems have evolved
      distinct crRNA biogenesis pathways that implicate highly sophisticated processing
      mechanisms. In Types I and III CRISPR-Cas systems, a specific endoribonuclease of
      the Cas6 family, either standalone or in a complex with other Cas proteins,
      cleaves the pre-crRNA within the repeat regions. In Type II systems, the trans
      acting small RNA (tracrRNA) base pairs with each repeat of the pre-crRNA to form
      a dual-RNA that is cleaved by the housekeeping RNase III in the presence of the
      protein Cas9. In this review, we present a detailed comparative analysis of pre
      crRNA recognition and cleavage mechanisms involved in the biogenesis of guide
      crRNAs in the three CRISPR-Cas types. 

PMID- 25994612
TI  - Severe vitamin D deficiency in patients with Kawasaki disease: a potential role
      in the risk to develop heart vascular abnormalities?
AB  - Twenty-five-hydroxyvitamin D (25(OH)-vitamin D) is crucial in the regulation of
      immunologic processes, but-although its deficiency has been reported in patients
      with different rheumatological disorders-no data are available for Kawasaki
      disease (KD). The goals of this study were to assess the serum levels of 25(OH)
      vitamin D in children with KD and evaluate the relationship with the eventual
      occurrence of KD-related vascular abnormalities. We evaluated serum 25(OH)
      vitamin D levels in 79 children with KD (21 females, 58 males, median age 4.9
      years, range 1.4-7.5 years) in comparison with healthy sex-/age-matched controls.
      A significantly higher percentage of KD patients (98.7 %) were shown to have
      reduced 25(OH)-vitamin D levels (<30 ng/mL) in comparison with controls (78.6 %,
      p < 0.0001). Furthermore, KD patients had severely low levels of 25(OH)-vitamin D
      than controls (9.17 +/- 4.94 vs 23.3 +/- 10.6 ng/mL, p < 0.0001), especially the
      subgroup who developed coronary artery abnormalities (4.92 +/- 1.36 vs 9.41 +/-
      4.95 ng/mL, p < 0.0001). In addition, serum 25(OH)-vitamin D levels correlated
      not only with erythrosedimentation rate (p < 0.0001), C-reactive protein (p <
      0.0001), hemoglobin level at KD diagnosis (p < 0.0001) but also with both
      coronary artery aneurysms (p = 0.005) and non-aneurysmatic cardiovascular lesions
      (p < 0.05). Low serum concentrations of 25(OH)-vitamin D might have a
      contributive role in the development of coronary artery complications observed in
      children with KD. 

PMID- 25994613
TI  - Evaluation of anti-cyclic citrullinated peptide antibodies may be beneficial in
      RF-negative juvenile idiopathic arthritis patients.
AB  - Despite the high diagnostic and prognostic performance in adult rheumatoid
      arthritis, the role of antibodies to cyclic citrullinated peptide (anti-CCP) in
      juvenile idiopathic arthritis (JIA) is controversial. Occurrence of anti-CCP was
      mainly seen in rheumatoid factor (RF)-positive polyarthritis patients. In the
      present study, our aim was to investigate the prevalence and significance of anti
      CCP for subjects with JIA in our population. We evaluated anti-CCP reactivity in
      the sera of 70 patients with various subtypes of JIA in a prospective cohort
      study. Anti-CCP titres were correlated with the evolution of joint involvement
      and the presence of joint damage. Nine JIA patients were seropositive for anti
      CCP with respect to the cut-off value of the test. In our cohort, 34 patients had
      a polyarticular joint disease, most of them being RF-negative (30/34, 88 %). All
      four RF-positive polyarthritis patients had high anti-CCP concentrations and an
      aggressive erosive disease. In the RF-negative JIA patients, anti-CCP reactivity
      was in lower titres but significantly associated with polyarticular joint
      involvement (p = 0.016) and also with the presence of joint damage (p < 0.001).
      Presence of anti-CCP, at both low and high concentration, was significantly
      associated with a more severe articular disease in our JIA patients.
      Investigating anti-CCP should clearly be taken into consideration even among
      patients with JIA subtypes other than RF-positive polyarthritis.

PMID- 25994614
TI  - [Shadows and errors of a law: the opinion of clinicians].
AB  - A new Italian law (81/14) recently established dismission of all Psychiatric
      Forensic Hospitals and the transferring of old and new "forensic" patients to the
      local Mental Health Department, at time in many instances in the same common
      settings of acute psychiatric services, community and territorial psychiatry
      mixed with "common" psychiatric patients. The preoccupation is high for
      communality of psychopaths, insane criminal patients and drug-dependent violent
      patients together with young first-episode schizophrenic patients, anorexic
      girls, older depressive patients, and so on. This change already introduced
      several problems with strong preoccupation among operators, other patients and
      public opinion as concerns both treatment efficiency and safety of the cure.

PMID- 25994615
TI  - [Experience-centred cognitive psychotherapy: towards a phenomenologically
      oriented therapy].
AB  - Post-rationalist cognitive psychotherapy (PRCP), developed by Vittorio Guidano,
      focuses on the relationship between subjective experience and reflective
      explanation. Although this is a powerful, innovative, and flexible treatment
      model, there are some aspects that deserve reflection and could be further
      developed. We propose a treatment model that integrates PRCP with some principles
      of phenomenology, i.e., experience has a meaning that precedes reflection; it is
      structured according to "manifestation rules" that connect feelings, thoughts,
      and actions; personal identity is grounded in the action and cannot be reduced to
      what remains identical throughout the life course. As in traditional PRCP, a key
      aspect of treatment is the examination of the interplay between experience and
      explanation. However, treatment focuses more on the understanding of experience
      than on its verbally mediated evaluation. Moreover, it aims not so much at
      revealing the rules through which the patient relates his experience to
      him/herself, as at bringing to light all the relevant aspects of the patient's
      experience, validating the experience by making explicit the links, enabling the
      patient to take hold of his/her experience, and leading him/her to learn how to
      understand it without the mediation of reflection. The knowledge of the
      tendencies, characteristic of each personal meaning organization, to find
      difficulties in grasping specific aspects of experience helps the therapist
      identify the sequences of experience that are not sufficiently articulated and
      understood. The main therapeutic procedures are identification, exploration,
      validation, and narrative reconfiguration of the experience that was not
      understood by the patient, in order to reduce the related feelings of strangeness
      and unfamiliarity, facilitate emotion regulation, and help the patient reflect
      and make choices in harmony with self-realization. Future research priorities
      include developing a treatment manual and testing the effectiveness of the
      proposed treatment model in a clinical trial. 

PMID- 25994616
TI  - [Functional magnetic resonance imaging in subjects at high risk for
      schizophrenia: a review].
AB  - Functional magnetic resonance (fMRI) has an important role in the study of the
      vulnerability to psychosis: it is an essential tool to search for endophenotypes
      that can let us to understand the pathophysiological mechanisms of schizophrenia
      and increase the ability to predict the onset of the illness. In this review are
      summarized results of the fMRI studies conducted on individuals at enhanced risk
      for developing psychosis, for clinical or genetic reasons. The cerebral activity
      in this kind of subjects appear in most cases more similar to that of individuals
      affected than to that of normal controls; this increases the possibility, in the
      future, for a diagnostic role of the cerebral activation. Nevertheless the
      technology is too young and the studies are too heterogeneous to reach conclusive
      results. 

PMID- 25994617
TI  - [Evaluation of the impact of the new version of a handbook to promote
      psychological wellbeing and emotional intelligence in the schools (students aged
      12-15)].
AB  - AIM: A recent study has demonstrated the effectiveness of a structured
      intervention based on a manual of mental health promotion for students of
      secondary schools developed by the Istituto Superiore di Sanita based on the
      "cooperative learning", the "life skills" and "self-efficacy"; unfortunately, the
      results were less significant than expected. The Authors made changes to the
      Handbook for Students simplifying the language to allow its use even in middle
      schools. The present study aims at evaluating the effectiveness of this new
      version of the manual that includes a notebook. METHODS: A pre-post study design
      was used with also experimental vs. control group comparison. Five classes were
      included in the experimental group and five in the control group belonging to 5
      different institutes. The efficacy has been established through several self
      filled questionnaires to assess improvement of skills (effective communication,
      goal-setting, problem solving), psychological well-being, perceived self-efficacy
      in the regulation of negative and positive emotions, irrational believes, and
      unhealthy lifestyles such as drinking and smoking. RESULTS: Significant
      improvements were observed in almost all dimensions evaluated with the exception
      of self-efficacy and irrational believes. Of particular importance were the
      improvements about skills (effective communication, goal-setting and problem
      solving), psychological well-being and in some behaviors "at risk" as the
      frequent involvement in fights and smoking habit. Overall, the improvement was
      greater than that observed in the first study by the same authors using the
      manual in the original version. CONCLUSIONS: The observed data confirm the
      effectiveness of this approach with better results if compared to previous
      studies because of the use of the new edition of the manual. One of the
      ingredient of success, in the opinion of the authors, was the use of this manual
      that includes a notebook that stimulates extracurricular exercises.

PMID- 25994618
TI  - [Factors affecting the choice of a family psychosocial intervention. A
      retrospective study from an experience of 8 years].
AB  - INTRODUCTION: Systematic studies have shown that the integration of
      pharmacological with psychosocial family treatments produces an improvement in
      clinical outcome with reduction of relapses, number and duration of
      hospitalizations. AIM: In the present study we wanted to investigate the presence
      of a possible association between household characteristics and the choice of
      joining a particular type of family intervention. MATERIALS AND METHODS: For this
      purpose, we performed a retrospective reconstruction of the therapy of a sample
      of 82 families treated with psychosocial family interventions for a period of 8
      years. This sample was divided into 3 subgroups according to the type of family
      intervention performed (sporadic consulting, psychoeducation to term, continuous
      psychoeducation). Socio-demographic and clinical variables, motivations for the
      access to treatment and the relationship with the service of the families were
      investigated by reading the medical records, the use of PSICHE and the
      administration of a questionnaire that we created for this purpose. RESULTS: Type
      of pathology and clinical severity of the patients were not related to the choice
      of the type of psychosocial intervention performed by the family. On the
      contrary, considerable importance in choosing the type of psychosocial family
      intervention--in terms of personal involvement, duration of the same and shared
      objectives--have both the presence of comorbidity for substance use disorder
      between patients, and the role of the operator sending, who cannot disregard the
      objectives to be pursued and their consistency with the overall purposes of the
      intervention.

PMID- 25994619
TI  - Reliability of a self-report Italian version of the AUDIT-C questionnaire, used
      to estimate alcohol consumption by pregnant women in an obstetric setting.
AB  - AIM: Alcohol consumption during pregnancy can result in a range of harmful
      effects on the developing foetus and newborn, called Fetal Alcohol Spectrum
      Disorders (FASD). The identification of pregnant women who use alcohol enables to
      provide information, support and treatment for women and the surveillance of
      their children. The AUDIT-C (the shortened consumption version of the Alcohol Use
      Disorders Identification Test) is used for investigating risky drinking with
      different populations, and has been applied to estimate alcohol use and risky
      drinking also in antenatal clinics. The aim of the study was to investigate the
      reliability of a self-report Italian version of the AUDIT-C questionnaire to
      detect alcohol consumption during pregnancy, regardless of its use as a screening
      tool. METHODS: The questionnaire was filled in by two independent consecutive
      series of pregnant women at the 38th gestation week visit in the two birth
      locations of the Local Health Authority of Treviso (Italy), during the years 2010
      and 2011 (n=220 and n=239). Reliability analysis was performed using internal
      consistency, item-total score correlations, and inter-item correlations. The
      "discriminatory power" of the test was also evaluated. Results. Overall, about
      one third of women recalled alcohol consumption at least once during the current
      pregnancy. The questionnaire had an internal consistency of 0.565 for the group
      of the year 2010, of 0.516 for the year 2011, and of 0.542 for the overall group.
      The highest item total correlations' coefficient was 0.687 and the highest inter
      item correlations' coefficient was 0.675. As for the discriminatory power of the
      questionnaire, the highest Ferguson's delta coefficient was 0.623. CONCLUSIONS:
      These findings suggest that the Italian self-report version of the AUDIT-C
      possesses unsatisfactory reliability to estimate alcohol consumption during
      pregnancy when used as self-report questionnaire in an obstetric setting.

PMID- 25994620
TI  - Cotard's Syndrome after breast surgery successfully treated with aripiprazole
      augmentation of escitalopram: a case report.
AB  - In 1880 the French neurologist Jules Cotard described a condition characterized
      by delusion of negation (nihilistic delusion) in a melancholia context. Recently,
      there has been a resurgence of interest in Cotard's syndrome (CS), but the
      nosographical figure of CS remains unclear. It isn't determined if it pertains to
      the delusional themes area or if it is related to the sense of immanent ruin in
      some depressive episodes. For these reasons CS has recently been supposed to be
      an intermediate form. Furthermore, since even less is known about secondary CS in
      subjects who had never suffered of psychiatric disorders, in the present case we
      report the development of a secondary CS in a female patient who underwent a
      lumpectomy for the removal of a benign fibroadenoma. The patient responded well
      to aripiprazole augmentation of escitalopram and totally remitted.

PMID- 25994623
TI  - Assessment of Laparoscopic Skills Performance: 2D Versus 3D Vision and Classic
      Instrument Versus New Hand-Held Robotic Device for Laparoscopy.
AB  - INTRODUCTION AND OBJECTIVES: Laparoscopic surgery has undeniable advantages, such
      as reduced postoperative pain, smaller incisions, and faster recovery. However,
      to improve surgeons' performance, ergonomic adaptations of the laparoscopic
      instruments and introduction of robotic technology are needed. The aim of this
      study was to ascertain the influence of a new hand-held robotic device for
      laparoscopy (HHRDL) and 3D vision on laparoscopic skills performance of 2
      different groups, naive and expert. MATERIALS AND METHODS: Each participant
      performed 3 laparoscopic tasks-Peg transfer, Wire chaser, Knot-in 4 different
      ways. With random sequencing we assigned the execution order of the tasks based
      on the first type of visualization and laparoscopic instrument. Time to complete
      each laparoscopic task was recorded and analyzed with one-way analysis of
      variance. RESULTS: Eleven experts and 15 naive participants were included. Three
      dimensional video helps the naive group to get better performance in Peg
      transfer, Wire chaser 2 hands, and Knot; the new device improved the execution of
      all laparoscopic tasks (P < .05). For expert group, the 3D video system benefited
      them in Peg transfer and Wire chaser 1 hand, and the robotic device in Peg
      transfer, Wire chaser 1 hand, and Wire chaser 2 hands (P < .05). CONCLUSION: The
      HHRDL helps the execution of difficult laparoscopic tasks, such as Knot, in the
      naive group. Three-dimensional vision makes the laparoscopic performance of the
      participants without laparoscopic experience easier, unlike those with experience
      in laparoscopic procedures.

PMID- 25994622
TI  - TLR ligand induced IL-6 counter-regulates the anti-viral CD8(+) T cell response
      during an acute retrovirus infection.
AB  - We have previously shown that Toll-like receptor (TLR) agonists contribute to the
      control of viral infection by augmenting virus-specific CD8(+) T-cell responses.
      It is also well established that signaling by TLRs results in the production of
      pro-inflammatory cytokines such as interleukin 6 (IL-6). However, how these pro
      inflammatory cytokines influence the virus-specific CD8(+) T-cell response during
      the TLR agonist stimulation remained largely unknown. Here, we investigated the
      role of TLR-induced IL-6 in shaping virus-specific CD8(+) T-cell responses in the
      Friend retrovirus (FV) mouse model. We show that the TLR agonist induced IL-6
      counter-regulates effector CD8(+) T-cell responses. IL-6 potently inhibited
      activation and cytokine production of CD8(+) T cells in vitro. This effect was
      mediated by a direct stimulation of CD8(+) T cells by IL-6, which induced
      upregulation of STAT3 phosphorylation and SOCS3 and downregulated STAT4
      phosphorylation and T-bet. Moreover, combining TLR stimulation and IL-6 blockade
      during an acute FV infection resulted in enhanced virus-specific CD8(+) T-cell
      immunity and better control of viral replication. These results have implications
      for our understanding of the role of TLR induced pro-inflammatory cytokines in
      regulating effector T cell responses and for the development of therapeutic
      strategies to overcome T cell dysfunction in chronic viral infections. 

PMID- 25994624
TI  - Cardiopulmonary exercise testing for predicting postoperative morbidity in
      patients undergoing hepatic resection surgery.
AB  - OBJECTIVES: Cardiopulmonary exercise testing (CPET) may predict which patients
      are at risk for adverse outcomes after major abdominal surgery. The primary aim
      of this study was to determine whether CPET variables are predicative of
      morbidity. METHODS: High-risk patients undergoing elective, one-stage, open
      hepatic resection were preoperatively assessed using CPET. Morbidity, as defined
      by the Postoperative Morbidity Survey (POMS), was assessed on postoperative day
      3. RESULTS: A total of 104 patients underwent preoperative CPET and were included
      in the analysis. Of these, 73 patients (70.2%) experienced postoperative
      morbidity. Oxygen consumption at anaerobic threshold (VO2 at AT, ml/kg/min) was
      the only CPET predictor of postoperative morbidity on multivariable analysis,
      with an area under the curve (AUC) of 0.66 [95% confidence interval (CI) 0.55
      0.76]. In patients requiring a major hepatic resection (three or more segments),
      a VO2 at AT of <10.2 ml/kg/min gave an AUC of 0.79 (95% CI 0.68-0.86) with 83.9%
      sensitivity and 52.0% specificity, 80.6% positive predictive value and 62.5%
      negative predictive value. CONCLUSIONS: The application of a cut-off value for
      VO2 at AT of <10.2 ml/kg/min in patients undergoing major hepatic resection may
      be useful for predicting which patients will experience morbidity.

PMID- 25994625
TI  - A strong pelvic floor is associated with higher rates of sexual activity in women
      with pelvic floor disorders.
AB  - INTRODUCTION AND HYPOTHESIS: We evaluated the associations between pelvic floor
      muscle strength and tone with sexual activity and sexual function in women with
      pelvic floor disorders. METHODS: This was a secondary analysis of a multicenter
      study of women with pelvic floor disorders from the USA and UK performed to
      validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA
      Revised (PISQ-IR). Participants were surveyed about whether they were sexually
      active and completed the PISQ-IR and the Female Sexual Function Index (FSFI)
      questionnaires to assess sexual function. Physical examinations included
      assessment of pelvic floor strength by the Oxford Grading Scale, and assessment
      of pelvic floor tone as per ICS guidelines. RESULTS: The cohort of 585 women was
      middle-aged (mean age 54.9 +/- 12.1) with 395 (67.5 %) reporting sexual activity.
      Women with a strong pelvic floor (n = 275) were more likely to report sexual
      activity than women with weak strength (n = 280; 75.3 vs 61.8 %, p < 0.001), but
      normal or hypoactive pelvic floor tone was not associated with sexual activity
      (68.8 vs 60.2 %, normal vs hypoactive, p = 0.08). After multivariable analysis, a
      strong pelvic floor remained predictive of sexual activity (OR 1.89, CI 1.18
      3.03, p < 0.01). Among sexually active women (n = 370), a strong pelvic floor was
      associated with higher scores on the PISQ-IR domain of condition impact
      (parameter estimate 0.20+/- 0.09, p = 0.04), and the FSFI orgasm domain (PE 0.51
      +/- 0.17, p = 0.004). CONCLUSION: A strong pelvic floor is associated with higher
      rates of sexual activity as well as higher sexual function scores on the
      condition impact domain of the PISQ-IR and the orgasm domain of the FSFI.

PMID- 25994626
TI  - Pre-departure preparation for international clinical work: a handbook.
AB  - International clinical experiences are increasingly popular among medical
      students, residents, fellows, and practitioners. Adequate pre-departure training
      is an integral part of a meaningful, productive, and safe international
      experience. At Johns Hopkins University School of Medicine, we have developed a
      pre-departure handbook to assist practitioners in preparing for global health
      work. The handbook draws from current global health education literature,
      existing handbooks, and expert experiences, and includes information about
      logistical and cultural preparations. While a pre-departure handbook cannot serve
      as a substitute for a comprehensive pre-departure training program, it can be a
      useful introduction to the pre-departure process. 

PMID- 25994627
TI  - Abdominopelvic kinesiotherapy for pelvic floor muscle training: a tested proposal
      in different groups.
AB  - INTRODUCTION AND HYPOTHESIS: This video's proposal was to present one of the
      pelvic floor muscle (PFM) training programs used in our research, and to study
      the effects of abdominopelvic kinesiotherapy on female PFM function. METHODS: A
      total of 82 women participated in this study, 11 nulliparous, 13 primiparous
      pregnant, 20 primiparous postpartum and 38 postmenopausal women, who were
      evaluated first by digital palpation, then by either electromyography or vaginal
      dynamometry to investigate their PFM strength, followed by ICIQ UI-SF and ICIQ
      OAB to evaluate urinary symptoms. This intervention protocol lasted for 60 min,
      three times a week, with a total of 10 sessions, and was supervised by a
      physiotherapist, using a gym ball, according to Marques and collaborators.
      RESULTS: A significant increase in PFM strength was observed by digital palpation
      in all groups. This finding was confirmed by electromyography in both pregnant (p
      = 0.0001) and postpartum (p = 0.0001) groups, as well as in 20 of the 38 women
      from the postmenopausal group (p = 0.003) then by vaginal dynamometry (p = 0.02)
      in the rest of the women (18) from the same group, with a concomitant decrease in
      urinary symptoms (p < 0.05). CONCLUSION: The abdominopelvic kinesiotherapy
      program promotes an increase in pelvic floor muscle strength and a decrease in
      urinary symptoms.

PMID- 25994629
TI  - When and how to discuss "do not resuscitate" decisions with patients.

PMID- 25994628
TI  - Pelvic floor muscle displacement during voluntary and involuntary activation in
      continent and incontinent women: a systematic review.
AB  - INTRODUCTION: Investigations of the dynamic function of female pelvic floor
      muscles (PFM) help us to understand the pathophysiology of stress urinary
      incontinence (SUI). Displacement measurements of PFM give insight into muscle
      activation and thus help to improve rehabilitation strategies. This systematic
      review (PROSPERO 2013: CRD42013006409) was performed to summarise the current
      evidence for PFM displacement during voluntary and involuntary activation in
      continent and incontinent women. METHODS: MEDLINE, EMBASE, Cochrane and
      SPORTDiscus databases were searched using selected terminology reflecting the
      PICO approach. Screening of Google Scholar and congress abstracts added to
      further information. Original articles investigating PFM displacement were
      included if they reported on at least one of the aims of the review, e.g.,
      method, test position, test activity, direction and quantification of
      displacement, as well as the comparison between continent and incontinent women.
      Titles and abstracts were screened by two reviewers. The papers included were
      reviewed by two individuals to ascertain whether they fulfilled the inclusion
      criteria and data were extracted on outcome parameters. RESULTS: Forty-two
      predominantly observational studies fulfilled the inclusion criteria. A variety
      of measurement methods and calculations of displacement was presented. The sample
      was heterogeneous concerning age, parity and continence status. Test positions
      and test activities varied among the studies. CONCLUSIONS: The findings summarise
      the present knowledge of PFM displacement, but still lack deeper comprehension of
      the SUI pathomechanism of involuntary, reflexive activation during functional
      activities. We therefore propose that future investigations focus on PFM dynamics
      during fast and stressful impact tasks.

PMID- 25994630
TI  - An amazing discovery: bird navigation based on olfaction.

PMID- 25994631
TI  - Characterization of the target of ivermectin, the glutamate-gated chloride
      channel, from Anopheles gambiae.
AB  - The use of insecticide-treated nets and indoor residual insecticides targeting
      adult mosquito vectors is a key element in malaria control programs. However,
      mosquito resistance to the insecticides used in these applications threatens
      malaria control efforts. Recently, the mass drug administration of ivermectin
      (IVM) has been shown to kill Anopheles gambiae mosquitoes and disrupt Plasmodium
      falciparum transmission in the field. We cloned the molecular target of IVM from
      A. gambiae, the glutamate-gated chloride channel (AgGluCl), and characterized its
      transcriptional patterns, protein expression and functional responses to
      glutamate and IVM. AgGluCl cloning revealed an unpredicted fourth splice isoform
      as well as a novel exon and splice site. The predicted gene products contained
      heterogeneity in the N-terminal extracellular domain and the intracellular loop
      region. Responses to glutamate and IVM were measured using two-electrode voltage
      clamp on Xenopus laevis oocytes expressing AgGluCl. IVM induced non-persistent
      currents in AgGluCl-a1 and did not potentiate glutamate responses. In contrast,
      AgGluCl-b was insensitive to IVM, suggesting that the AgGluCl gene could produce
      IVM-sensitive and -insensitive homomultimers from alternative splicing. AgGluCl
      isoform-specific transcripts were measured across tissues, ages, blood feeding
      status and sex, and were found to be differentially transcribed across these
      physiological variables. Lastly, we stained adult, female A. gambiae for GluCl
      expression. The channel was expressed in the antenna, Johnston's organ,
      supraesophageal ganglion and thoracic ganglia. In summary, we have characterized
      the first GluCl from a mosquito, A. gambiae, and described its unique activity
      and expression with respect to it as the target of the insecticide IVM. 

PMID- 25994632
TI  - Mosquitocidal properties of IgG targeting the glutamate-gated chloride channel in
      three mosquito disease vectors (Diptera: Culicidae).
AB  - The glutamate-gated chloride channel (GluCl) is a highly sensitive insecticide
      target of the avermectin class of insecticides. As an alternative to using
      chemical insecticides to kill mosquitoes, we tested the effects of purified
      immunoglobulin G (IgG) targeting the extracellular domain of GluCl from Anopheles
      gambiae (AgGluCl) on the survivorship of three key mosquito disease vectors:
      Anopheles gambiae s.s., Aedes aegypti and Culex tarsalis. When administered
      through a single blood meal, anti-AgGluCl IgG reduced the survivorship of A.
      gambiae in a dose-dependent manner (LC50: 2.82 mg ml(-1), range 2.68-2.96 mg ml(
      1)) but not A. aegypti or C. tarsalis. We previously demonstrated that AgGluCl is
      only located in tissues of the head and thorax of A. gambiae. To verify that
      AgGluCl IgG is affecting target antigens found outside the midgut, we injected it
      directly into the hemocoel via intrathoracic injection. A single, physiologically
      relevant concentration of anti-AgGluCl IgG injected into the hemocoel equally
      reduced mosquito survivorship of all three species. To test whether anti-AgGluCl
      IgG was entering the hemocoel of each of these mosquitoes, we fed mosquitoes a
      blood meal containing anti-AgGluCl IgG and subsequently extracted their
      hemolymph. We only detected IgG in the hemolymph of A. gambiae, suggesting that
      resistance of A. aegypti and C. tarsalis to anti-AgGluCl IgG found in blood meals
      is due to deficient IgG translocation across the midgut. We predicted that anti
      AgGluCl IgG's mode of action is by antagonizing GluCl activity. To test this
      hypothesis, we fed A. gambiae blood meals containing anti-AgGluCl IgG and the
      GluCl agonist ivermectin (IVM). Anti-AgGluCl IgG attenuated the mosquitocidal
      effects of IVM, suggesting that anti-AgGluCl IgG antagonizes IVM-induced
      activation of GluCl. Lastly, we stained adult, female A. aegypti and C. tarsalis
      for GluCl expression. Neuronal GluCl expression in these mosquitoes was similar
      to previously reported A. gambiae GluCl expression; however, we also discovered
      GluCl staining on the basolateral surface of their midgut epithelial cells,
      suggesting important physiological differences in Culicine and Anopheline
      mosquitoes. 

PMID- 25994633
TI  - Eye-independent, light-activated chromatophore expansion (LACE) and expression of
      phototransduction genes in the skin of Octopus bimaculoides.
AB  - Cephalopods are renowned for changing the color and pattern of their skin for
      both camouflage and communication. Yet, we do not fully understand how
      cephalopods control the pigmented chromatophore organs in their skin and change
      their body pattern. Although these changes primarily rely on eyesight, we found
      that light causes chromatophores to expand in excised pieces of Octopus
      bimaculoides skin. We call this behavior light-activated chromatophore expansion
      (or LACE). To uncover how octopus skin senses light, we used antibodies against r
      opsin phototransduction proteins to identify sensory neurons that express r-opsin
      in the skin. We hypothesized that octopus LACE relies on the same r-opsin
      phototransduction cascade found in octopus eyes. By creating an action spectrum
      for the latency to LACE, we found that LACE occurred most quickly in response to
      blue light. We fit our action spectrum data to a standard opsin curve template
      and estimated the lambdamax of LACE to be 480 nm. Consistent with our hypothesis,
      the maximum sensitivity of the light sensors underlying LACE closely matches the
      known spectral sensitivity of opsin from octopus eyes. LACE in isolated
      preparations suggests that octopus skin is intrinsically light sensitive and that
      this dispersed light sense might contribute to their unique and novel patterning
      abilities. Finally, our data suggest that a common molecular mechanism for light
      detection in eyes may have been co-opted for light sensing in octopus skin and
      then used for LACE. 

PMID- 25994634
TI  - Dynamic digestive physiology of a female reproductive organ in a polyandrous
      butterfly.
AB  - Reproductive traits experience high levels of selection because of their direct
      ties to fitness, often resulting in rapid adaptive evolution. Much of the work in
      this area has focused on male reproductive traits. However, a more comprehensive
      understanding of female reproductive adaptations and their relationship to male
      characters is crucial to uncover the relative roles of sexual cooperation and
      conflict in driving co-evolutionary dynamics between the sexes. We focus on the
      physiology of a complex female reproductive adaptation in butterflies and moths:
      a stomach-like organ in the female reproductive tract called the bursa copulatrix
      that digests the male ejaculate (spermatophore). Little is known about how the
      bursa digests the spermatophore. We characterized bursa proteolytic capacity in
      relation to female state in the polyandrous butterfly Pieris rapae. We found that
      the virgin bursa exhibits extremely high levels of proteolytic activity.
      Furthermore, in virgin females, bursal proteolytic capacity increases with time
      since eclosion and ambient temperature, but is not sensitive to the pre-mating
      social environment. Post copulation, bursal proteolytic activity decreases
      rapidly before rebounding toward the end of a mating cycle, suggesting active
      female regulation of proteolysis and/or potential quenching of proteolysis by
      male ejaculate constituents. Using transcriptomic and proteomic approaches, we
      report identities for nine proteases actively transcribed by bursal tissue and/or
      expressed in the bursal lumen that may contribute to observed bursal proteolysis.
      We discuss how these dynamic physiological characteristics may function as female
      adaptations resulting from sexual conflict over female remating rate in this
      polyandrous butterfly. 

PMID- 25994635
TI  - Visual phototransduction components in cephalopod chromatophores suggest dermal
      photoreception.
AB  - Cephalopod mollusks are renowned for their colorful and dynamic body patterns,
      produced by an assemblage of skin components that interact with light. These may
      include iridophores, leucophores, chromatophores and (in some species)
      photophores. Here, we present molecular evidence suggesting that cephalopod
      chromatophores - small dermal pigmentary organs that reflect various colors of
      light - are photosensitive. RT-PCR revealed the presence of transcripts encoding
      rhodopsin and retinochrome within the retinas and skin of the squid Doryteuthis
      pealeii, and the cuttlefish Sepia officinalis and Sepia latimanus. In D. pealeii,
      Gqalpha and squid TRP channel transcripts were present in the retina and in all
      dermal samples. Rhodopsin, retinochrome and Gqalpha transcripts were also found
      in RNA extracts from dissociated chromatophores isolated from D. pealeii dermal
      tissues. Immunohistochemical staining labeled rhodopsin, retinochrome and Gqalpha
      proteins in several chromatophore components, including pigment cell membranes,
      radial muscle fibers, and sheath cells. This is the first evidence that
      cephalopod dermal tissues, and specifically chromatophores, may possess the
      requisite combination of molecules required to respond to light. 

PMID- 25994636
TI  - Adhesive pad differentiation in Drosophila melanogaster depends on the Polycomb
      group gene Su(z)2.

PMID- 25994637
TI  - Editorial: An emerging immunogenomics and computational approach for peptide
      vaccinology: rational design of peptide vaccines.

PMID- 25994638
TI  - Docking modes of BB-3497 into the PDF active site--a comparison of the pure MM
      and QM/MM based docking strategies.
AB  - Peptide deformylase (PDF) has emerged as an important antibacterial drug target.
      Considerable effort is being directed toward developing peptidic and non-peptidic
      inhibitors for this metalloprotein. In this work, the known peptidic inhibitor BB
      3497 and its various ionization and tautomeric states are evaluated for their
      inhibition efficiency against PDF using a molecular mechanics (MM) approach as
      well as a mixed quantum mechanics/molecular mechanics (QM/MM) approach, with an
      aim to understand the interactions in the binding site. The evaluated Gibbs
      energies of binding with the mixed QM/MM approach are shown to have the best
      predictive power. The experimental pose is found to have the most negative Gibbs
      energy of binding, and also the smallest strain energy. A quantum mechanical
      evaluation of the active site reveals the requirement of strong chelation by the
      ligand with the metal ion. The investigated ligand chelates the metal ion through
      the two oxygens of its reverse hydroxamate moiety, particularly the N-O(-)
      oxygen, forming strong covalent bonds with the metal ion, which is penta
      coordinated. In the uninhibited state, the metal ion is tetrahedrally
      coordinated, and hence chelation with the inhibitor is associated with an
      increase of the metal ion coordination. Thus, the strong binding of the ligand at
      the binding site is accounted for.

PMID- 25994639
TI  - 3D-QSAR analysis on ATR protein kinase inhibitors using CoMFA and CoMSIA.
AB  - Ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase is an
      attractive anticancer target. In this study, comparative molecular field analysis
      (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were
      performed on a series of aminopyrazine ATR inhibitors. The models generated by
      CoMFA had a cross-validated coefficient (q(2)) of 0.752 and a regression
      coefficient (r(2)) of 0.947. The CoMSIA models had a q(2) of 0.728 and an r(2) of
      0.936. The reasonable quantitative structure-activity relationship model showed
      robust predictive ability. The contour map provided guidelines for building novel
      virtual compounds based on compound NO.40. In addition, the 3D structure of ATR
      was modeled by homology modeling. Molecular dynamic simulations were employed to
      optimize the structure. The docking results offered insights into the
      interactions between the inhibitors and the active site for potent analysis. This
      study provides useful guidance for the discovery of more potent compounds.

PMID- 25994640
TI  - A combined cheminformatics and computational approach for the prediction of anti
      HIV small molecules.
AB  - Acquired immunodeficiency syndrome (AIDS) is one of the most devastating diseases
      of current century which is caused by the human immunodeficiency virus (HIV).
      Although great efforts have been done to fight the virus, the need of new
      therapeutics candidates of any kind still remains. This process needs huge time
      and experimental endeavor. However, Computer-aided techniques and can speed up
      the procedure. Currently, cheminformatics tools have proven to be extremely
      valuable in pharmaceutical research. In the past few decades, a huge number of
      different molecular descriptors were designed to describe chemical molecules in a
      quantitative way to make it easy to use them for computational studies. Herein,
      we present a computational study of anti-HIV small molecules test by the National
      Cancer Institute (NCI) to introduce the most efficient molecular descriptors for
      anti-HIV activity. In this regard a dataset of 199 highly active anti-HIV and 174
      inactive compounds were defined by 905 molecular descriptors. Data were
      classified using Random Forest algorithm and the most important molecular
      descriptors were introduced as the parameters responsible for representing anti
      HIV activity. Applying the mentioned computational and cheminformatics methods,
      it is possible to predict the anti-HIV activity of any given small molecule with
      high accuracy.

PMID- 25994642
TI  - Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles
      of acrosomal proteins.
AB  - The interaction of sperm with the egg's extracellular matrix, the zona pellucida
      (ZP) is the first step of the union between male and female gametes. The
      molecular mechanisms of this process have been studied for the past six decades
      with the results obtained being both interesting and confusing. In this article,
      we describe our recent work, which attempts to address two lines of questions
      from previous studies. First, because there are numerous ZP binding proteins
      reported by various researchers, how do these proteins act together in sperm-ZP
      interaction? Second, why do a number of acrosomal proteins have ZP affinity? Are
      they involved mainly in the initial sperm-ZP binding or rather in anchoring
      acrosome reacting/reacted spermatozoa to the ZP? Our studies reveal that a number
      of ZP binding proteins and chaperones, extracted from the anterior sperm head
      plasma membrane, coexist as high molecular weight (HMW) complexes, and that these
      complexes in capacitated spermatozoa have preferential ability to bind to the ZP.
      Zonadhesin (ZAN), known as an acrosomal protein with ZP affinity, is one of these
      proteins in the HMW complexes. Immunoprecipitation indicates that ZAN interacts
      with other acrosomal proteins, proacrosin/acrosin and sp32 (ACRBP), also present
      in the HMW complexes. Immunodetection of ZAN and proacrosin/acrosin on
      spermatozoa further indicates that both proteins traffic to the sperm head
      surface during capacitation where the sperm acrosomal matrix is still intact, and
      therefore they are likely involved in the initial sperm-ZP binding step. 

PMID- 25994644
TI  - Association of polymorphisms of A260G and A386G in DAZL gene with male
      infertility: a meta-analysis and systemic review.
AB  - To investigate the association of single nucleotide polymorphism 260 and 386
      (SNP260 and SNP386) gene with male infertility, an electronic search was
      performed to identify case-control studies evaluating the relationship of SNP260
      or SNP386 of deleted in azoospermia-like (DAZL) and male infertility. Review
      Manager 5 was used to process the meta-analysis and other statistical analysis. A
      total of 139 records were retrieved, of which 13 case-control studies with total
      2715 patients and 1835 normozoospermic men were included. SNP260 was found not to
      play a functional role in male oligo/azoospermia either for Caucasians or for
      Asians. But for SNP386, models of allele (A/G), dominant (AA/AG + GG), co
      dominant (AA/AG) and super-dominant (AA + GG/AG) had a strong correlation to
      spermatogenic failure with related odds ratio being 0.15 (95% confidence interval
      [95% CI] 0.07 to 0.34, P < 0.00001), 0.16 (95% CI 0.07 to 0.35, P < 0.00001),
      0.15 (95% CI 0.06 to 0.33, P < 0.00001) and 0.15 (95% CI 0.06 to 0.33, P <
      0.00001), respectively. Moreover, this correlation was only found in the Chinese
      Han population (decreasing around 85% risk of oligo/azoospermia infertility) and
      not found in India, Japan, and Caucasian countries. Our analysis demonstrated
      that SNP260 of DAZL did not contribute to oligo/azoospermia while SNP386 was
      correlated to male infertility. However, this correlation was only found in China
      with a country-specific and ethnicity-specific manner. 

PMID- 25994645
TI  - Advantages of using the CRISPR/Cas9 system of genome editing to investigate male
      reproductive mechanisms using mouse models.
AB  - Gene disruption technology has long been beneficial for the study of male
      reproductive biology. However, because of the time and cost involved, this
      technology was not a viable method except in specialist laboratories. The advent
      of the CRISPR/Cas9 system of gene disruption has ushered in a new era of genetic
      investigation. Now, it is possible to generate gene-disrupted mouse models in
      very little time and at very little cost. This Highlight article discusses the
      application of this technology to study the genetics of male fertility and looks
      at some of the future uses of this system that could be used to reveal the
      essential and nonessential genetic components of male reproductive mechanisms. 

PMID- 25994643
TI  - Robotic radical prostatectomy in high-risk prostate cancer: current perspectives.
AB  - Around 20%-30% of patients diagnosed with prostate cancer (PCa) still have high
      risk PCa disease (HRPC) that requires aggressive treatment. Treatment of HRPC is
      controversial, and multimodality therapy combining surgery, radiation therapy,
      and androgen deprivation therapy have been suggested. There has been a trend
      toward performing radical prostatectomy (RP) in HRPC and currently, robot
      assisted laparoscopic RP (RARP) has become the most common approach. Number of
      publications related to robotic surgery in HRPC is limited in the literature.
      Tissue and Tumor characteristics might be different in HRPC patients compared to
      low-risk group and increased surgical experience for RARP is needed. Due to the
      current literature, RARP seems to have similar oncologic outcomes including
      surgical margin positivity, biochemical recurrence and recurrence-free survival
      rates, additional cancer therapy needs and lymph node (LN) yields with similar
      complication rates compared to open surgery in HRPC. In addition, decreased blood
      loss, lower rates of blood transfusion and shorter duration of hospital stay seem
      to be the advantages of robotic surgery in this particular patient group. RARP in
      HRPC patients seems to be safe and technically feasible with good intermediate
      term oncologic results, acceptable morbidities, excellent short-term surgical and
      pathological outcomes and satisfactory functional results. 

PMID- 25994646
TI  - The 12 (th) International Symposium on Spermatology.

PMID- 25994647
TI  - Putting things in place for fertilization: discovering roles for importin
      proteins in cell fate and spermatogenesis.
AB  - Importin proteins were originally characterized for their central role in protein
      transport through the nuclear pores, the only intracellular entry to the nucleus.
      This vital function must be tightly regulated to control access by transcription
      factors and other nuclear proteins to genomic DNA, to achieve appropriate
      modulation of cellular behaviors affecting cell fate. Importin-mediated
      nucleocytoplasmic transport relies on their specific recognition of cargoes, with
      each importin binding to distinct and overlapping protein subsets. Knowledge of
      importin function has expanded substantially in regard to three key developmental
      systems: embryonic stem cells, muscle cells and the germ line. In the decade
      since the potential for regulated nucleocytoplasmic transport to contribute to
      spermatogenesis was proposed, we and others have shown that the importins that
      ferry transcription factors into the nucleus perform additional roles, which
      control cell fate. This review presents key findings from studies of mammalian
      spermatogenesis that reveal potential new pathways by which male fertility and
      infertility arise. These studies of germline genesis illuminate new ways in which
      importin proteins govern cellular differentiation, including via directing
      proteins to distinct intracellular compartments and by determining cellular
      stress responses. 

PMID- 25994648
TI  - Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and alpha
      adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH.
AB  - The aim of this systematic review is to determine the comparative effectiveness
      and safety of phosphodiesterase 5 inhibitors (PDE5-Is) and alpha-blockers used
      alone or combined for the treatment of lower urinary tract symptoms (LUTS) due to
      benign prostatic hyperplasia (BPH). An electronic search of PubMed, Cochrane
      Library and Embase up to January 2014 was performed to identify randomized
      controlled trials comparing the efficacy and safety of PDE5-Is and alpha-blockers
      for treatment of lower urinary tract symptoms due to benign prostatic
      hyperplasia, which assessed IPSS score, maximum flow rate, postvoided residual
      urine, quality of life and Erectile Function (IIEF) score as outcomes. Data were
      analyzed by fixed or random effect models using Cochrane Collaboration review
      manager software. A total of 12 studies were included. Our novel data
      demonstrated that there was a trend that alpha-blockers were more efficacious
      than PDE5-Is on decreasing IPSS score and increasing maximum flow rate. alpha
      blockers were significantly more effective than PDE5-Is on reduction of
      postvoided residual urine with a mean difference of 3.67 (95% CI 1.56 to 5.77, P
      = 0.0006) and PDE5-Is showed greater effect than alpha-blockers on increasing
      IIEF score with a mean difference of 9.82 (95% CI 3.80 to 15.85, P = 0.001). In
      conclusion, our novel data demonstrated that PDE5-Is plus ABs ranked the highest
      on the improvement of LUTS/BPH. PDE5-Is monotherapy was also effective in this
      kind of disorder except less reduction of PVR than ABs. In addition, both
      combined- or mono-therapy were safe. 

PMID- 25994649
TI  - The prognostic value of clinical and pathologic features in nonmetastatic
      operable male breast cancer.
AB  - Compared with female breast cancer, male breast cancer is a rare disease, and the
      relationship between clinical/pathologic features and prognosis is controversial,
      or even largely unknown. In this study, we performed a retrospective analysis
      using clinical and pathologic data from 109 nonmetastatic operable male breast
      cancer patients treated from January 1996 to December 2011 at Tianjin Medical
      University Cancer Institute and Hospital. Log-rank test showed that lower tumor
      stage, no lymph node involvement, and positive estrogen/progesterone receptor
      status were good predictors of both disease-free survival and overall survival on
      univariate analysis. However, hormonotherapy is only a good predictive factor of
      disease-free survival, and not of overall survival. In addition, based on a Cox
      proportional hazard regression model, only lymph node involvement, and
      estrogen/progesterone receptor status were statistically significant predictive
      factors on multivariate analysis. Our results demonstrated that although adjuvant
      systemic therapy is used extensively in male breast cancer patients and prognosis
      has improved over the last few decades, lymph node involvement, and
      estrogen/progesterone receptor status are still the most important prognostic
      factors. A prospective multi-center study with a larger sample size is urgently
      needed to further understand male breast cancer. 

PMID- 25994650
TI  - Spermatogonial stem cells: Progress and prospects.
AB  - Twenty years ago, the transplantation of spermatogonial stem cells (SSCs) from a
      mouse to other recipient mice was shown to be feasible, which clearly
      demonstrated the functional identity of SSCs. Since then, several important new
      findings and other technical developments have followed, which included a new
      hypothesis on their cell kinetics and spermatogonial hierarchy in the testis, a
      culture method allowing their self-renewal and proliferation, a testis tissue
      organ culture method, which induced their complete differentiation up to sperm,
      and the in vitro induction of germ cells from embryonic stem cells and induced
      pluripotent stem cells. These advancements reinforced or advanced our
      understanding of this unique cell. Nonetheless, there are many unresolved
      questions in the study of spermatogonial stem cells and a long road remains until
      these cells can be used clinically in reproductive medicine. 

PMID- 25994651
TI  - The application of color Doppler flow imaging in the diagnosis and therapeutic
      effect evaluation of erectile dysfunction.
AB  - We aim to investigate the correlations between hemodynamic parameters, penile
      rigidity grading, and the therapeutic effects of phosphodiesterase type 5
      inhibitors using color Doppler flow imaging after intracavernosal injection in
      patients with erectile dysfunction. This study involved 164 patients. After
      intracavernosal injection with a mixture of papaverine (60 mg), prostaglandin E 1
      (10 mg), and lidocaine (2%, 0.5-1 ml), the penile vessels were assessed using
      color Doppler flow imaging. Penile rigidity was classified based on the Erection
      Hardness Score system as Grades 4, 3, 2 or 1 (corresponding to Schramek Grades V
      to II). Then, the patients were given oral sildenafil (50-100 mg) and scored
      according to the International Index of Erectile Function (IIEF-5) questionnaire.
      The number of patients with penile rigidities of Schramek Grades II to V was 14,
      18, 21, and 111, respectively. The IIEF-5 score was positively correlated with
      the refilling index of the penile cavernosal artery (r = 0.79, P< 0.05), the peak
      systolic velocity (r = 0.45, P< 0.05), and penile rigidity (r = 0.75, P< 0.05),
      and was negatively correlated with the end diastolic velocity (r = -0.74, P<
      0.05). For patients with erectile dysfunction, both the IIEF-5 score after
      sildenafil administration, which is correlated with penile rigidity, and the
      hemodynamic parameters detected using color Doppler flow imaging may predict the
      effects of phosphodiesterase type 5 inhibitor treatment and could provide a
      reasonable model for the targeted-treatment of erectile dysfunction. 

PMID- 25994653
TI  - Chemically induced DNA damage and sperm and oocyte repair machinery: the story
      gets more interesting.
AB  - Assisted reproductive technologies have allowed us to bypass elusive questions of
      how spermatogenesis truly works so that end results, namely conception, can be
      achieved quickly and efficiently. Yet, reproductive biology, andrology, and
      molecular mutagenesis have not completely abandoned unanswered questions about
      how spermatogenesis unfolds, where things can go wrong in the process, and what
      are the impacts on the conceptus when sperm are somehow defective. Additional
      questions stem from the recognition that model systems are only approximations of
      how human reproduction actually happens in a world replete with extraneous
      exposures, from micronutrients to everyday chemicals. New evidence is adding to
      our understanding of how exceptionally stage-dependent spermatogenesis is, and
      how genotoxic exposures at exact stages differentially affect sperm cells.
      Recently reported new mouse model evidence demonstrates that postfertilization,
      oocytes misrepair sperm DNA defects that allow chromosomal structural aberrations
      to persist in the conceptus. These findings give new perspectives on both
      intrinsic actions of DNA repair checkpoints and on critical windows of sperm
      vulnerability to mutagenicity and toxicity.

PMID- 25994652
TI  - The role of Dicer1 in the male reproductive tract.
AB  - Dicer1 is an RNase III enzyme necessary for microRNA (miRNA) biogenesis, as it
      cleaves pre-miRNAs into mature miRNAs. miRNAs are important regulators of gene
      expression. In recent years, several miRNA-independent roles of Dicer1 have been
      identified. They include the production of endogenous small interfering RNAs,
      detoxifying retrotransposon-derived transcripts, and binding to new targets;
      messenger RNAs and long noncoding RNAs. Further, in this review, the functional
      significance of Dicer1 in the male reproductive tract is discussed. Conditional
      Dicer1 knock-out mouse models have demonstrated a requisite role for Dicer in
      male fertility. Deletion of Dicer1 from somatic or germ cells in the testis cause
      spermatogenic problems rendering male mice infertile. The lack of Dicer1 in the
      proximal epididymis causes dedifferentiation of the epithelium, with unbalanced
      sex steroid receptor expression, defects in epithelial lipid homeostasis, and
      subsequent male infertility. In addition, Dicer1 ablation from the prostate leads
      to increased apoptosis of the differentiated luminal cells, followed by
      epithelial hypotrophy of the ventral prostate. However, further studies are
      needed to clarify which functions of Dicer1 are responsible for the observed
      phenotypes in the male reproductive tract. 

PMID- 25994654
TI  - Phosphorylation of Izumo1 and Its Role in Male Infertility.
AB  - Izumo1 is a testis-specific gene product, whose function is essential for sperm
      egg fusion. Throughout its lifespan, Izumo1 is posttranslationally modified,
      being both N-linked glycosylated on its extracellular domain and phosphorylated
      on the intracellular C-terminal tail. Within the caput regions of the rat
      epididymis, two phosphorylation events have been documented. However, as sperm
      pass through the epididymis, this cytoplasmic portion of Izumo1 has been shown to
      contain up to seven phosphorylation sites. Remarkably, in the rat, in correlation
      with these events, Izumo1 undergoes sub-cellular re-location, moving from the
      head/tail regions of the spermatozoa, to a predominantly equatorial segment
      location once they have reached the caudal end of the epididymis. 

PMID- 25994656
TI  - Will too much kidney function kill you: just as none at all?

PMID- 25994655
TI  - PDE7 inhibitor TC3.6 ameliorates symptomatology in a model of primary progressive
      multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: cAMP plays an important role in the transduction of
      signalling pathways involved in neuroprotection and immune regulation. Control of
      the levels of this nucleotide by inhibition of cAMP-specific PDEs such as PDE7
      may affect the pathological processes of neuroinflammatory diseases like multiple
      sclerosis (MS). In the present study, we evaluated the therapeutic potential of
      the selective PDE7 inhibitor, TC3.6, in a model of primary progressive multiple
      sclerosis (PPMS), a rare and severe variant of MS. EXPERIMENTAL APPROACH:
      Theiler's murine encephalomyelitis virus-induced demyelinated disease (TMEV-IDD)
      is one of the models used to validate the therapeutic efficacy of new drugs in
      MS. As recent studies have analysed the effect of PDE7 inhibitors in the EAE
      model of MS, here the TMEV-IDD model was used to test their efficacy in a
      progressive variant of MS. Mice were subjected to two protocols of TC3.6
      administration: on the pre-symptomatic phase and once the disease was
      established. KEY RESULTS: Treatment with TC3.6 ameliorated the disease course and
      improved motor deficits of infected mice. This was associated with down
      regulation of microglial activation and reduced cellular infiltrates. Decreased
      expression of pro-inflammatory mediators such as COX-2 and the cytokines, IL
      1beta, TNF-alpha, IFN-gamma and IL-6 in the spinal cord of TMEV-infected mice was
      also observed after TC3.6 administration. CONCLUSION: These findings support the
      importance of PDE7 inhibitors, and specifically TC3.6, as a novel class of agents
      with therapeutic potential for PPMS. Preclinical studies are needed to determine
      whether their effects translate into durable clinical benefits.

PMID- 25994657
TI  - Con: Biomarkers in glomerular diseases: putting the cart before the wheel?
AB  - Biomarkers have been increasingly sought to improve diagnosis as well as predict
      prognosis and/or response to therapy. However, they should not replace sound
      clinical judgment and therapeutic measures. The present article aims to highlight
      the issues with biomarker research in three selected entities. In focal segmental
      glomerulosclerosis, many studies fail to differentiate cases of primary versus
      secondary forms leading to conclusions that are uninterpretable. Biomarkers have
      also been sought to predict development of diabetic nephropathy but this research
      should not supersede efforts aimed to optimize treatment of diabetes. Finally, in
      lupus nephritis (LN), biomarkers so far have failed to prove value in clinical
      practice. The concept of immunological remission should be added to the concept
      of clinical remission when judging response to immunosuppressive therapy in LN.
      In addition, the appropriate time frame for remission to occur should be
      reconsidered. 

PMID- 25994658
TI  - Opponent's comments.

PMID- 25994660
TI  - Opponent's comments.

PMID- 25994659
TI  - Pro: 'The usefulness of biomarkers in glomerular diseases'. The problem: moving
      from syndrome to mechanism--individual patient variability in disease
      presentation, course and response to therapy.
AB  - The diagnosis and treatment decisions in glomerular disease are principally based
      on renal pathology and nonspecific clinical laboratory measurements such as serum
      creatinine and urine protein. Using these classification approaches, patients
      have marked variability in rate of progression and response to therapy, exposing
      a significant number of patients to toxicity without benefit. Additionally,
      clinical trials are at risk of not being able to detect an efficacious therapy in
      relevant subgroups as patients with shared clinical-pathologic diagnoses have
      heterogeneous underlying pathobiology. To change this treatment paradigm,
      biomarkers that reflect the molecular mechanisms underlying the clinical
      pathologic diagnoses are needed. Recent progress to identify such biomarkers has
      been aided by advances in molecular profiling, large-scale data generation and
      multi-scalar data integration, including prospectively collected clinical data.
      This article reviews the evolving success stories in glomerular disease
      biomarkers across the genotype-phenotype continuum and highlights opportunities
      to transition to precision medicine in glomerular disease. 

PMID- 25994661
TI  - Moderator's view: Biomarkers in glomerular diseases--translated into patient care
      or lost in translation?

PMID- 25994662
TI  - High estimated glomerular filtration rate is associated with coronary artery
      calcification in middle-aged Korean men without chronic kidney disease.
AB  - BACKGROUND: High estimated glomerular filtration rate (eGFR) as well as low eGFR
      is associated with cardiovascular morbidity and mortality. Vascular calcification
      is a suggested link between low eGFR and worse cardiovascular outcome. However,
      the association between high eGFR and vascular calcification is not known. The
      aim of this study is to investigate the relationship between high eGFR and
      coronary artery calcification (CAC). METHODS: This cross-sectional study analyzed
      middle-aged Korean men in whom coronary artery calcium scores (CACS) and eGFR
      were measured as part of a health examination program in Korea. Participants with
      underlying chronic kidney disease (CKD), cardiovascular disease (CVD) and cancer
      were excluded. CAC was defined as a CACS >100. RESULTS: Among 6986 subjects [age
      48.1 (46.5-50.5) years], 321 (4.6%) participants had CAC. The percentages of
      participants with CAC were 5.7, 3.8, 4.9 and 6.6 in groups with eGFR (mL/min/1.73
      m(2)) of 60 ~ 74, 75 ~ 89, 90 ~ 104 and 105 ~ max, respectively. According to
      multivariate analysis, the odds ratio for CAC in the group with eGFR of 105 ~ max
      compared with the group with eGFR of 75 ~ 89 was 2.52 (1.67-3.79, P < 0.001)
      after adjustment for age, body mass index, diabetes, hypertension, systolic blood
      pressure, glucose, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, triglyceride, hsCRP, calcium, phosphorus, current smoking, alcohol
      intake and vigorous exercise frequency. CONCLUSIONS: High eGFR is associated with
      CAC in middle-aged Korean men without CKD. Further studies are needed to verify a
      causal relationship and clarify the role of high eGFR in the development of CVD.

PMID- 25994664
TI  - The effects on ovarian activity of ulipristal acetate when 'quickstarting' a
      combined oral contraceptive pill: a prospective, randomized, double-blind
      parallel-arm, placebo-controlled study.
AB  - STUDY QUESTION: What is the effect on ovarian activity of a preceding intake of
      ulipristal acetate (UPA) when starting a combined oral contraceptive (COC) in the
      mid- to late-follicular phase of the cycle? SUMMARY ANSWER: This study shows that
      UPA does not affect the ability of the COC to induce ovarian quiescence. WHAT IS
      KNOWN ALREADY: UPA is a progesterone receptor modulator that is available for
      emergency contraception (EC). In theory, UPA could alter the effectiveness of
      hormonal contraception started immediately following it and vice versa. Current
      guidelines regarding quick starting a COC following UPA are based on expert
      opinion only. STUDY DESIGN, SIZE, DURATION: A double-blind, randomized, placebo
      controlled trial was conducted at three separate sites, Edinburgh (Scotland),
      Stockholm (Sweden) and Groningen (the Netherlands), over a 5-month period in
      2012. Healthy female volunteers were randomized to take either UPA or an
      identically packaged placebo, at mid-cycle (once a lead ovarian follicle was
      determined to be >13 mm on transvaginal ultrasound imaging). Participants were
      randomized by a computer-generated randomization schedule, allocated by
      sequential, sealed envelopes. All women then started 21 days of the same COC the
      following day. The study was designed to show non-inferiority of UPA compared
      with placebo in terms of the proportion of women attaining ovarian quiescence, as
      measured by the Hoogland scoring system, while taking COC.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 76 women were recruited over
      the three sites, Edinburgh (n = 18), Stockholm (n = 13), Groningen (n = 45) and
      received either UPA (n = 39) or placebo (n = 37). MAIN RESULTS AND THE ROLE OF
      CHANCE: There were no significant differences in demographic characteristics of
      women in the UPA and placebo groups. Among the 76 participants treated, 47
      (61.8%) reached quiescence and 25 (32.9%) ovulated. There were no significant
      differences between the groups in the odds ratio (OR) of reaching ovarian
      quiescence or not; OR 0.97 (95% CI: 0.39-2.46). All women who reached quiescence
      had done so after taking COCs for 14 days. LIMITATIONS, REASONS FOR CAUTION: The
      main limitations of the study were that measurements of follicle size and blood
      tests were performed every 2-3 days and so it was not possible to determine the
      actual day that follicle rupture occurred for the women who ovulated.
      Furthermore, the ultrasonography was conducted by a number of investigators at
      the sites which may introduce error in the form of inter-observer variability in
      measurements of follicle growth. Finally, the findings of the study cannot be
      extrapolated to other combined hormonal methods of contraception such as the
      patch or ring, nor to progestogen- only methods of contraception. WIDER
      IMPLICATIONS OF THE FINDINGS: This study provides evidence to suggest that UPA
      does not affect the ability of the COC to induce ovarian quiescence. However,
      this study design cannot determine whether the COC affects the ability of UPA to
      delay ovulation. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by HRA
      Pharma Paris, France. C.K., S.T.C. and K.G.D. have received funds for conducting
      research studies and lectures for HRA Pharma. C.K. is director of a contract
      research organization (Dinox). The remaining authors declare no conflicts of
      interests. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT01569113.

PMID- 25994665
TI  - No association between body mass index and sperm DNA integrity.
AB  - STUDY QUESTION: Is overweight associated with impaired sperm DNA integrity?
      SUMMARY ANSWER: High body mass index (BMI) is not associated with impaired sperm
      DNA integrity as assessed by the DNA Fragmentation Index (DFI). WHAT IS KNOWN
      ALREADY: Previous studies, based on fewer subjects and including mainly
      subfertile men, have shown conflicting results regarding the influence of
      overweight and obesity on sperm DNA integrity. STUDY DESIGN, SIZE, DURATION: This
      cross-sectional study was based on semen samples from 1503 men from the general
      population. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included two cohorts
      (cohort A and B) of military recruits (n = 275, n = 304, respectively), one group
      (cohort C) of fertile men and men without known fertility problems (n = 724), and
      one group (cohort D) of men between 19 and 40 years without known fertility
      problems (n = 200). In all cohorts, data were available on BMI, DFI as measured
      by the sperm chromatin structure assay (SCSA), standard semen characteristics,
      and potential confounders (age, abstinence time, smoking habits). The subjects
      were categorized according to BMI into four groups: underweight (<18.5 kg/m(2)),
      normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese
      (>=30.0 kg/m(2)). Using a linear regression model, the inter-group differences in
      DFI were calculated. Furthermore with the normal-weight group as the reference,
      the odds ratios (ORs) for DFI > 20% and DFI > 30%, were calculated for the other
      groups. Calculations were made for the material as a whole and after exclusion of
      cohort C which included proven fertile men. MAIN RESULTS AND THE ROLE OF CHANCE:
      We found that normal-weight men had significantly higher DFI than overweight men,
      with a mean difference of 1.13% (95% CI: 1.05-1.22%); P = 0.001). Overweight men
      had a reduced risk of having DFI >= 20% and DFI >= 30%, compared with normal
      weight men; adjusted odds ratio (OR) = 0.61 (95% CI: 0.42-0.88; P < 0.01) and
      adjusted OR = 0.48 (95% CI: 0.28-0.84; P < 0.01), respectively. When excluding
      cohort C, the statistical significance was lost. Regarding standard semen
      parameters, we found that obese men had a higher percentage of progressive motile
      spermatozoa than normal-weight men; mean difference 1.15% (95% CI: 1.02-1.30%, P
      < 0.05) but the significance was lost when excluding cohort C. All other standard
      semen parameters were unaffected by BMI. LIMITATIONS, REASONS FOR CAUTION: A main
      limitation might be the cross-sectional nature of the data. Furthermore our study
      included a significant proportion of men with proven fertility (75% of cohort C,
      n = 550), and could therefore be biased toward fertility. WIDER IMPLICATIONS OF
      THE FINDINGS: Our study indicates that overweight per se is not associated with a
      higher level of sperm DNA damage. STUDY FUNDING/COMPETING INTERESTS: This
      research has been given grants from the following: EU 5th and 7th framework
      program (Inuendo and Clear projects, [Contracts no. QLK4-CT-2001-00202 and FP7
      ENV-2008-1-226217)]), the Swedish Research Council (Grants No. 2007-2590, 521
      2004-6072 and 521-2002-3907); the Swedish Governmental Funding for Clinical
      Research, Skane county council's research and development foundation, MAS Funds,
      University Hospital MAS Foundation in Malmo, Crafoordska Fund, Ove Tulefjords
      Fund, Foundation for Urological Research, Fundacion Federico SA, and Gunnar
      Nilssons Cancer Fund. The authors declare that there are no conflicts of
      interest.

PMID- 25994666
TI  - Epididymitis: ascending infection restricted by segmental boundaries.
AB  - STUDY QUESTION: Is the regionalization of epididymitis related to epididymal
      segmentation? SUMMARY ANSWER: We show for the first time that luminal ascent of
      bacteria is strictly gated by epididymal segment boundaries, involving ductal
      constriction adjacent to the infected area. WHAT IS KNOWN ALREADY: The epididymal
      duct is a continuous, unbranched tube, coiled into segments that are divided by
      connective tissue septa. Sonographic analysis indicates that swelling associated
      with epididymitis is predominant in the cauda region. Epididymal segmentation has
      never been investigated in the context of pathological alterations. STUDY DESIGN,
      SIZE, AND DURATION: We analyzed segment-specific changes in the epididymal duct
      in a mouse model and in men. In the mouse epididymitis model (3 days post
      infection, injection of bacteria into the lumen of the vas deferens), two
      Escherichia coli strains were tested: a uropathogenic strain CFT073 (UPEC, n = 7)
      and a fecal non-pathogenic strain NPEC470 (NPEC, n = 5). Two control groups:
      phosphate-buffered saline, sham-treated animals (n = 4) and untreated mice (n =
      8). In addition, segmentation was verified by ex vivo injection of dye into the
      interstitial spaces of untreated mouse epididymides. Histological findings were
      compared with specimens from epididymitis patients (n = 10, age range 14-78,
      median 60 years) who underwent surgical intervention; control: samples from
      patients without epididymitis (n = 16, age range 38-87, median 73 years).
      PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We investigated the ascending
      infections by detailed histological analysis in correlation with local infection
      status in a mouse epididymitis model. As a proof of concept, rare patient
      material from two archives was analyzed: epididymides from patients who underwent
      surgical intervention for persisting epididymitis, and for control,
      histologically normal epididymides from men who underwent orchiectomy for therapy
      of prostatic carcinoma. MAIN RESULTS AND THE ROLE OF CHANCE: Luminal ascent of E.
      coli in mice was strictly gated by epididymal segment boundaries. In the mouse
      model, both strains of E. coli were detected exclusively in the distal cauda
      segment associated with damage of the epithelium and muscle layer. Ductal
      constriction occurred in the non-infected upstream segments of infected area,
      putatively blocking further luminal ascent of bacteria in UPEC-infected animals.
      Corresponding histological and morphological changes were found in epididymitis
      patients. The caput region was found to be unaffected in patients and the mouse
      model. LIMITATIONS, REASONS FOR CAUTION: Patient samples represented advanced
      cases of epididymitis that made surgical intervention necessary. WIDER
      IMPLICATIONS OF THE FINDINGS: Our data demonstrate the impact of epididymal
      segmentation, presumably a protective response mechanism against infectious
      invasion and bacterial ascent, during epididymitis and affirm the importance of
      rapid intervention. STUDY FUNDING/COMPETING INTERESTS: This work was supported by
      grants from the State of Hessen (LOEWE-MIBIE) and the DFG (KFO 181). The authors
      have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: No clinical
      trial involved.

PMID- 25994667
TI  - Relationship between diminished ovarian reserve and mitochondrial biogenesis in
      cumulus cells.
AB  - STUDY QUESTION: What part do mitochondria play in cases of diminished ovarian
      reserve (DOR)? SUMMARY ANSWER: Mitochondrial biogenesis in cumulus cells may be
      linked with impaired oocyte competence in patients with DOR. WHAT IS KNOWN
      ALREADY: DOR, one of the causes of infertility even in young women, is
      characterized by the depletion of the ovarian pool associated with a decline in
      oocyte competence. Mitochondria, which play a role in oocyte quality, could be
      involved in the pathogenesis of DOR. The study of cumulus cells offers an
      interesting non-invasive approach for evaluating oocyte quality and the metabolic
      processes on which it depends. If mitochondrial dysfunction is involved in DOR,
      it is likely to have an impact on the functioning of cumulus cells. STUDY DESIGN,
      SIZE, DURATION: This is an observational study of 74 immature oocyte-cumulus
      complexes retrieved from 47 women undergoing in vitro fertilization with
      intracytoplasmic sperm injection at the University Hospital of Angers, France,
      from March 2013 to March 2014. The women were divided into two groups: one group
      included 26 women with DOR, and the other, which included 21 women with a normal
      ovarian reserve (NOR), served as a control group. PARTICIPANTS/MATERIALS,
      SETTINGS, METHODS: The oocyte mitochondrial content and the average mitochondrial
      content of the cumulus cells were assessed by mitochondrial (mt)DNA
      quantification using a quantitative real-time PCR technique. Microfluidic-based
      quantitative RT-PCR assays were used to quantify the expression of 13 genes
      involved in mitochondrial functions such as apoptosis and antioxidant activity or
      in mitochondrial biogenesis. We used orthogonal partial least-squares
      discriminant analysis (OPLS-DA) to distinguish between the DOR group and the NOR
      group of patients, and an OPLS model to predict the value of the oocyte mtDNA
      content that could be used as a critical marker of oocyte quality. MAIN RESULTS
      AND THE ROLE OF CHANCE: The OPLS-DA model showed a good predictive capability (Q2
      = 0.543). Using the variable importance in projection (VIP) metric we found three
      mitochondrial variables distinguishing the DOR group from the NOR group of
      patients, i.e. the oocyte mtDNA content (VIP = 0.92), the cumulus cell mtDNA
      content (VIP = 0.95) and the expression in cumulus cells of peroxisome
      proliferator-activated receptor gamma coactivator 1 alpha (PPARGC-1A) (VIP =
      1.10), all of which were lower in the DOR group than in the NOR group of
      patients. The OPLS model was able to satisfactorily predict the oocyte mtDNA
      content in only the NOR group of patients (Q2 = 0.506). We found four new
      variables positively linked to the oocyte mitochondrial mass, i.e. the cumulus
      cell mtDNA content (VIP = 1.19), and the expression in cumulus cells of three
      factors of mitochondrial biogenesis: polymerase gamma (POLG) (VIP = 2.13), optic
      atrophy 1 (OPA1) (VIP = 1.89) and the transcription factor associated with
      mitochondria (TFAM) (VIP = 1.32). LIMITATIONS, REASONS OF CAUTION: This is a
      descriptive study. Because of ethical concerns in human clinical practice, this
      study has been performed only on immature oocytes and corresponding cumulus
      cells, which are usually discarded during in vitro fertilization procedures.
      WIDER IMPLICATIONS OF THE FINDINGS: Cumulus cells may govern mitochondrial
      biogenesis, creating an adequate oocyte mitochondrial pool to promote embryonic
      development. The alteration of this process in patients with DOR may account for
      the impairment of oocyte quality. This suggests that some mitochondrial
      characteristics of cumulus cells may serve as indicators of oocyte competence and
      that oocyte quality may be improved by products enhancing mitochondrial
      biogenesis. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant
      from the University Hospital of Angers, France: 'Appel d'offre interne a la
      recherche 2014'. TRIAL REGISTRATION NUMBER: N/A.

PMID- 25994668
TI  - The best source of isolated stromal cells for the artificial ovary: medulla or
      cortex, cryopreserved or fresh?
AB  - STUDY QUESTION: What is the best source of ovarian cells for the artificial
      ovary: medulla or cortex, cryopreserved or fresh? SUMMARY ANSWER: Ovarian cells
      from fresh medullary tissue, which can be isolated in larger numbers, show higher
      viability and are able to improve graft vascularization. WHAT IS KNOWN ALREADY:
      In a previous study, addition of endothelial cells along with ovarian cells was
      found to be crucial for formation of a well-vascularized ovary-like structure.
      This study is the first to evaluate both the effect of cryopreservation and the
      source of ovarian tissue on isolated ovarian cells. STUDY DESIGN, SIZE, DURATION:
      Prospective experimental study in an academic research unit using ovarian tissue
      from seven patients undergoing surgery for benign gynecologic disease.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissue was retrieved from seven
      patients, with one half processed as fresh (fresh group) and the other half
      frozen and thawed before processing (frozen group). In each group, ovarian cells
      from the cortex and medulla were isolated separately, and their viability was
      tested using a calcein AM/ethidium homodimer viability assay. Fifty thousand
      cells were then encapsulated in fibrin and grafted to peritoneal pockets in nude
      mice (14 in all). Grafts recovered after 7 days were analyzed by
      immunohistochemistry for the presence of ovarian cells (vimentin), proliferation
      (Ki67) and graft vascularization (double CD34). Cell apoptosis was analyzed by
      TUNEL assay. MAIN RESULTS AND THE ROLE OF CHANCE: Cryopreservation decreased
      ovarian cell yield (-2804 cells/mg, P = 0.015) and viability (-9.72%, P = 0.052)
      before grafting and had a considerable (5-fold, P = 0.2) but non-significant
      negative impact on ovarian cell presence in grafts. The medulla yielded many more
      cells (+3841 cells/mg, P < 0.001) with higher viability (+18.23%, P < 0.001) than
      did the cortex. Moreover, grafts with cells from the medulla exhibited a
      statistically significant 6.44- and 2.47-fold increase in human and total
      vascular surface area, respectively. P-values were adjusted for multiple testing
      using the Benjamini-Hochberg method to achieve a 10% false discovery rate and
      adjusted P-values < 0.1 were therefore considered significant. LIMITATIONS,
      REASONS FOR CAUTION: Pilot study involving a limited number of experiments. WIDER
      IMPLICATIONS OF THE FINDINGS: Knowing that fresh medullary tissue is the best
      source of stromal cells is important for construction of the artificial ovary, as
      isolated follicles require structural support and a rich vascular network for
      their survival and development. STUDY FUNDING/COMPETING INTERESTS: This work was
      supported by grants from the Fonds National de la Recherche Scientifique de
      Belgique (5/4/150/5 and 7.4518.12F), Fonds Speciaux de Recherche, Fondation Saint
      Luc and Foundation Against Cancer, and donations from Mr Pietro Ferrero, Baron
      Frere and Viscount Philippe de Spoelberch. None of the authors have any
      conflicting interests to declare.

PMID- 25994670
TI  - Environmental fluctuations restrict eco-evolutionary dynamics in predator-prey
      system.
AB  - Environmental fluctuations, species interactions and rapid evolution are all
      predicted to affect community structure and their temporal dynamics. Although the
      effects of the abiotic environment and prey evolution on ecological community
      dynamics have been studied separately, these factors can also have interactive
      effects. Here we used bacteria-ciliate microcosm experiments to test for eco
      evolutionary dynamics in fluctuating environments. Specifically, we followed
      population dynamics and a prey defence trait over time when populations were
      exposed to regular changes of bottom-up or top-down stressors, or combinations of
      these. We found that the rate of evolution of a defence trait was significantly
      lower in fluctuating compared with stable environments, and that the defence
      trait evolved to lower levels when two environmental stressors changed
      recurrently. The latter suggests that top-down and bottom-up changes can have
      additive effects constraining evolutionary response within populations. The
      differences in evolutionary trajectories are explained by fluctuations in
      population sizes of the prey and the predator, which continuously alter the
      supply of mutations in the prey and strength of selection through predation.
      Thus, it may be necessary to adopt an eco-evolutionary perspective on studies
      concerning the evolution of traits mediating species interactions. 

PMID- 25994669
TI  - Habitual action video game playing is associated with caudate nucleus-dependent
      navigational strategies.
AB  - The habitual playing of video games is associated with increased grey matter and
      activity in the striatum. Studies in humans and rodents have shown an inverse
      relationship between grey matter in the striatum and hippocampus. We investigated
      whether action video game playing is also associated with increased use of
      response learning strategies during navigation, known to be dependent on the
      caudate nucleus of the striatum, when presented in a dual solution task. We
      tested 26 action video game players (actionVGPs) and 33 non-action video game
      players (nonVGPs) on the 4-on-8 virtual maze and a visual attention event-related
      potential (ERP) task, which elicits a robust N-2-posterior-controlateral (N2pc)
      component. We found that actionVGPs had a significantly higher likelihood of
      using a response learning strategy (80.76%) compared to nonVGPs (42.42%).
      Consistent with previous evidence, actionVGPs and nonVGPs differed in the way
      they deployed visual attention to central and peripheral targets as observed in
      the elicited N2pc component during an ERP visual attention task. Increased use of
      the response strategy in actionVGPs is consistent with previously observed
      increases in striatal volume in video game players (VGPs). Using response
      strategies is associated with decreased grey matter in the hippocampus. Previous
      studies have shown that decreased volume in the hippocampus precedes the onset of
      many neurological and psychiatric disorders. If actionVGPs have lower grey matter
      in the hippocampus, as response learners normally do, then these individuals
      could be at increased risk of developing neurological and psychiatric disorders
      during their lifetime. 

PMID- 25994671
TI  - Infection of male rats with Toxoplasma gondii results in enhanced delay aversion
      and neural changes in the nucleus accumbens core.
AB  - Rats infected with the protozoan parasite Toxoplasma gondii exhibit reduced
      avoidance of predator odours. This behavioural change is likely to increase
      transmission of the parasite from rats to cats. Here, we show that infection with
      T. gondii increases the propensity of the infected rats to make more impulsive
      choices, manifested as delay aversion in an intertemporal choice task.
      Concomitantly, T. gondii infection causes reduction in dopamine content and
      neuronal spine density of the nucleus accumbens core, but not of the nucleus
      accumbens shell. These results are consistent with a role of the nucleus
      accumbens dopaminergic system in mediation of choice impulsivity and goal
      directed behaviours. Our observations suggest that T. gondii infection in rats
      causes a syndromic shift in related behavioural constructs of innate aversion and
      making foraging decisions. 

PMID- 25994672
TI  - Organic fields sustain weed metacommunity dynamics in farmland landscapes.
AB  - Agro-ecosystems constitute essential habitat for many organisms. Agricultural
      intensification, however, has caused a strong decline of farmland biodiversity.
      Organic farming (OF) is often presented as a more biodiversity-friendly practice,
      but the generality of the beneficial effects of OF is debated as the effects
      appear often species- and context-dependent, and current research has highlighted
      the need to quantify the relative effects of local- and landscape-scale
      management on farmland biodiversity. Yet very few studies have investigated the
      landscape-level effects of OF; that is to say, how the biodiversity of a field is
      affected by the presence or density of organically farmed fields in the
      surrounding landscape. We addressed this issue using the metacommunity framework,
      with weed species richness in winter wheat within an intensively farmed landscape
      in France as model system. Controlling for the effects of local and landscape
      structure, we showed that OF leads to higher local weed diversity and that the
      presence of OF in the landscape is associated with higher local weed biodiversity
      also for conventionally farmed fields, and may reach a similar biodiversity level
      to organic fields in field margins. Based on these results, we derive indications
      for improving the sustainable management of farming systems. 

PMID- 25994673
TI  - Avian responses to selective logging shaped by species traits and logging
      practices.
AB  - Selective logging is one of the most common forms of forest use in the tropics.
      Although the effects of selective logging on biodiversity have been widely
      studied, there is little agreement on the relationship between life-history
      traits and tolerance to logging. In this study, we assessed how species traits
      and logging practices combine to determine species responses to selective
      logging, based on over 4000 observations of the responses of nearly 1000 bird
      species to selective logging across the tropics. Our analysis shows that species
      traits, such as feeding group and body mass, and logging practices, such as time
      since logging and logging intensity, interact to influence a species' response to
      logging. Frugivores and insectivores were most adversely affected by logging and
      declined further with increasing logging intensity. Nectarivores and granivores
      responded positively to selective logging for the first two decades, after which
      their abundances decrease below pre-logging levels. Larger species of omnivores
      and granivores responded more positively to selective logging than smaller
      species from either feeding group, whereas this effect of body size was reversed
      for carnivores, herbivores, frugivores and insectivores. Most importantly,
      species most negatively impacted by selective logging had not recovered
      approximately 40 years after logging cessation. We conclude that selective timber
      harvest has the potential to cause large and long-lasting changes in avian
      biodiversity. However, our results suggest that the impacts can be mitigated to a
      certain extent through specific forest management strategies such as lengthening
      the rotation cycle and implementing reduced impact logging. 

PMID- 25994674
TI  - Context-dependent 'safekeeping' of foraging tools in New Caledonian crows.
AB  - Several animal species use tools for foraging, such as sticks to extract embedded
      arthropods and honey, or stones to crack open nuts and eggs. While providing
      access to nutritious foods, these behaviours may incur significant costs, such as
      the time and energy spent searching for, manufacturing and transporting tools.
      These costs can be reduced by re-using tools, keeping them safe when not needed.
      We experimentally investigated what New Caledonian crows do with their tools
      between successive prey extractions, and whether they express tool 'safekeeping'
      behaviours more often when the costs (foraging at height), or likelihood
      (handling of demanding prey), of tool loss are high. Birds generally took care of
      their tools (84% of 176 prey extractions, nine subjects), either trapping them
      underfoot (74%) or storing them in holes (26%)--behaviours we also observed in
      the wild (19 cases, four subjects). Moreover, tool-handling behaviour was context
      dependent, with subjects: keeping their tools safe significantly more often when
      foraging at height; and storing tools significantly more often in holes when
      extracting more demanding prey (under these conditions, foot-trapping proved
      challenging). In arboreal environments, safekeeping can prevent costly tool
      losses, removing a potentially important constraint on the evolution of habitual
      and complex tool behaviour.

PMID- 25994676
TI  - Plasticity in thermal tolerance has limited potential to buffer ectotherms from
      global warming.
AB  - Global warming is increasing the overheating risk for many organisms, though the
      potential for plasticity in thermal tolerance to mitigate this risk is largely
      unknown. In part, this shortcoming stems from a lack of knowledge about global
      and taxonomic patterns of variation in tolerance plasticity. To address this
      critical issue, we test leading hypotheses for broad-scale variation in ectotherm
      tolerance plasticity using a dataset that includes vertebrate and invertebrate
      taxa from terrestrial, freshwater and marine habitats. Contrary to expectation,
      plasticity in heat tolerance was unrelated to latitude or thermal seasonality.
      However, plasticity in cold tolerance is associated with thermal seasonality in
      some habitat types. In addition, aquatic taxa have approximately twice the
      plasticity of terrestrial taxa. Based on the observed patterns of variation in
      tolerance plasticity, we propose that limited potential for behavioural
      plasticity (i.e. behavioural thermoregulation) favours the evolution of greater
      plasticity in physiological traits, consistent with the 'Bogert effect'. Finally,
      we find that all ectotherms have relatively low acclimation in thermal tolerance
      and demonstrate that overheating risk will be minimally reduced by acclimation in
      even the most plastic groups. Our analysis indicates that behavioural and
      evolutionary mechanisms will be critical in allowing ectotherms to buffer
      themselves from extreme temperatures. 

PMID- 25994675
TI  - Climate mediates the effects of disturbance on ant assemblage structure.
AB  - Many studies have focused on the impacts of climate change on biological
      assemblages, yet little is known about how climate interacts with other major
      anthropogenic influences on biodiversity, such as habitat disturbance. Using a
      unique global database of 1128 local ant assemblages, we examined whether climate
      mediates the effects of habitat disturbance on assemblage structure at a global
      scale. Species richness and evenness were associated positively with temperature,
      and negatively with disturbance. However, the interaction among temperature,
      precipitation and disturbance shaped species richness and evenness. The effect
      was manifested through a failure of species richness to increase substantially
      with temperature in transformed habitats at low precipitation. At low
      precipitation levels, evenness increased with temperature in undisturbed sites,
      peaked at medium temperatures in disturbed sites and remained low in transformed
      sites. In warmer climates with lower rainfall, the effects of increasing
      disturbance on species richness and evenness were akin to decreases in
      temperature of up to 9 degrees C. Anthropogenic disturbance and ongoing climate
      change may interact in complicated ways to shape the structure of assemblages,
      with hot, arid environments likely to be at greatest risk. 

PMID- 25994677
TI  - Sensory-based niche partitioning in a multiple predator - multiple prey
      community.
AB  - Many predators and parasites eavesdrop on the communication signals of their
      prey. Eavesdropping is typically studied as dyadic predator-prey species
      interactions; yet in nature, most predators target multiple prey species and most
      prey must evade multiple predator species. The impact of predator communities on
      prey signal evolution is not well understood. Predators could converge in their
      preferences for conspicuous signal properties, generating competition among
      predators and natural selection on particular prey signal features.
      Alternatively, predator species could vary in their preferences for prey signal
      properties, resulting in sensory-based niche partitioning of prey resources. In
      the Neotropics, many substrate-gleaning bats use the mate-attraction songs of
      male katydids to locate them as prey. We studied mechanisms of niche partitioning
      in four substrate-gleaning bat species and found they are similar in morphology,
      echolocation signal design and prey-handling ability, but each species preferred
      different acoustic features of male song in 12 sympatric katydid species. This
      divergence in predator preference probably contributes to the coexistence of many
      substrate-gleaning bat species in the Neotropics, and the substantial diversity
      in the mate-attraction signals of katydids. Our results provide insight into how
      multiple eavesdropping predator species might influence prey signal evolution
      through sensory-based niche partitioning. 

PMID- 25994679
TI  - Social learning and the replication process: an experimental investigation.
AB  - Human cultural traits typically result from a gradual process that has been
      described as analogous to biological evolution. This observation has led
      pioneering scholars to draw inspiration from population genetics to develop a
      rigorous and successful theoretical framework of cultural evolution. Social
      learning, the mechanism allowing information to be transmitted between
      individuals, has thus been described as a simple replication mechanism. Although
      useful, the extent to which this idealization appropriately describes the actual
      social learning events has not been carefully assessed. Here, we used a
      specifically developed computer task to evaluate (i) the extent to which social
      learning leads to the replication of an observed behaviour and (ii) the
      consequences it has for fitness landscape exploration. Our results show that
      social learning does not lead to a dichotomous choice between disregarding and
      replicating social information. Rather, it appeared that individuals combine and
      transform information coming from multiple sources to produce new solutions. As a
      consequence, landscape exploration was promoted by the use of social information.
      These results invite us to rethink the way social learning is commonly modelled
      and could question the validity of predictions coming from models considering
      this process as replicative. 

PMID- 25994678
TI  - Three spectrally distinct photoreceptors in diurnal and nocturnal Australian
      ants.
AB  - Ants are thought to be special among Hymenopterans in having only dichromatic
      colour vision based on two spectrally distinct photoreceptors. Many ants are
      highly visual animals, however, and use vision extensively for navigation. We
      show here that two congeneric day- and night-active Australian ants have three
      spectrally distinct photoreceptor types, potentially supporting trichromatic
      colour vision. Electroretinogram recordings show the presence of three spectral
      sensitivities with peaks (lambdamax) at 370, 450 and 550 nm in the night-active
      Myrmecia vindex and peaks at 370, 470 and 510 nm in the day-active Myrmecia
      croslandi. Intracellular electrophysiology on individual photoreceptors confirmed
      that the night-active M. vindex has three spectral sensitivities with peaks
      (lambdamax) at 370, 430 and 550 nm. A large number of the intracellular
      recordings in the night-active M. vindex show unusually broad-band spectral
      sensitivities, suggesting that photoreceptors may be coupled. Spectral
      measurements at different temporal frequencies revealed that the ultraviolet
      receptors are comparatively slow. We discuss the adaptive significance and the
      probability of trichromacy in Myrmecia ants in the context of dim light vision
      and visual navigation. 

PMID- 25994680
TI  - Correction to: Genetic analysis of hair samples attributed to yeti, bigfoot and
      other anomalous primates.

PMID- 25994681
TI  - A reformulation of the Lambda-Phi diagram for the prediction of ocean acoustic
      fluctuation regimes.
AB  - The Lambda-Phi diagram was a tool introduced in the late 1970s to predict ocean
      acoustic fluctuation regimes termed unsaturated, partially saturated, and fully
      saturated, where internal wave sound speed fluctuations play a dominant role. The
      Lambda-Phi parameters reflect, respectively, the strength of diffraction and the
      root-mean-square phase fluctuation along a ray path. Oceanographic knowledge of
      the small scale part of the internal wave spectrum and high angle Fresnel zone
      formulations now allow a more stable and accurate calculation of these
      parameters. An empirical relation between the variance of log-intensity and
      Lambda-Phi provides a more accurate border between the unsaturated regime and
      stronger fluctuations. The diagram is consistent with six short range, deep water
      experiments in the Pacific, Atlantic, and Arctic oceans with frequencies ranging
      from 75 to 16 000 Hz. The utility of the Lambda-Phi diagram is that it provides
      one of the few means to inter-compare experiments at different geographic
      locations, and at different frequencies and ranges. 

PMID- 25994682
TI  - Acoustic detection of biosonar activity of deep diving odontocetes at Josephine
      Seamount High Seas Marine Protected Area.
AB  - The temporal occurrence of deep diving cetaceans in the Josephine Seamount High
      Seas Marine Protected Area (JSHSMPA), south-west Portugal, was monitored using a
      passive acoustic recorder. The recorder was deployed on 13 May 2010 at a depth of
      814 m during the North Atlantic Treaty Organization Centre for Maritime Research
      and Experimentation cruise "Sirena10" and recovered on 6 June 2010. The recorder
      was programmed to record 40 s of data every 2 min. Acoustic data analysis, for
      the detection and classification of echolocation clicks, was performed using
      automatic detector/classification systems: M3R (Marine Mammal Monitoring on Navy
      Ranges), a custom matlab program, and an operator-supervised custom matlab
      program to assess the classification performance of the detector/classification
      systems. M3R CS-SVM algorithm contains templates to detect beaked whales, sperm
      whales, blackfish (pilot and false killer whales), and Risso's dolphins. The
      detections of each group of odontocetes was monitored as a function of time.
      Blackfish and Risso's dolphins were detected every day, while beaked whales and
      sperm whales were detected almost every day. The hourly distribution of
      detections reveals that blackfish and Risso's dolphins were more active at night,
      while beaked whales and sperm whales were more active during daylight hours. 

PMID- 25994683
TI  - Automated detection of broadband clicks of freshwater fish using spectro-temporal
      features.
AB  - Large scale networks of embedded wireless sensor nodes can passively capture
      sound for species detection. However, the acoustic recordings result in large
      amounts of data requiring in-network classification for such systems to be
      feasible. The current state of the art in the area of in-network bioacoustics
      classification targets narrowband or long-duration signals, which render it
      unsuitable for detecting species that emit impulsive broadband signals. In this
      study, impulsive broadband signals were classified using a small set of spectral
      and temporal features to aid in their automatic detection and classification. A
      prototype system is presented along with an experimental evaluation of automated
      classification methods. The sound used was recorded from a freshwater invasive
      fish in Australia, the spotted tilapia (Tilapia mariae). Results show a high
      degree of accuracy after evaluating the proposed detection and classification
      method for T. mariae sounds and comparing its performance against the state of
      the art. Moreover, performance slightly improves when the original signal was
      down-sampled from 44.1 to 16 kHz. This indicates that the proposed method is well
      suited for detection and classification on embedded devices, which can be
      deployed to implement a large scale wireless sensor network for automated species
      detection. 

PMID- 25994684
TI  - Evoked-potential recovery during double click stimulation in a beluga whale:
      implications for biosonar gain control.
AB  - Auditory evoked potentials (AEPs) were recorded in a beluga whale Delphinapterus
      leucas using a double-pulse stimulation paradigm, specifically measuring the
      recovery (release from masking) of the second (test) response as a function of
      delay after the first (conditioning) pulse at various levels of the conditioning
      and test stimuli. The conditioning/test stimulus level ratio influenced the
      recovery time (the higher the ratio, the longer the recovery). This interrelation
      was used to evaluate the intensity/time trade in release from forward masking.
      Trade was evaluated as 32.2 dB per time decade. Data were considered as
      simulating interactions between the transmitted pulse and echo during
      echolocation, assuming that a transmitted sonar pulse produces forward masking of
      the echo response. With increased target distance, the attenuation of the echo
      may be compensated by the release from masking. According to the model, the
      compensation results in substantial stabilization of the echo response even if
      the intensity/time trade of release from masking is not precisely equal to the
      rate of echo attenuation with distance. 

PMID- 25994685
TI  - Material properties of Pacific hake, Humboldt squid, and two species of
      myctophids in the California Current.
AB  - Material properties of the flesh from three fish species (Merluccius productus,
      Symbolophorus californiensis, and Diaphus theta), and several body parts of the
      Humboldt squid (Dosidicus gigas) collected from the California Current ecosystem
      were measured. The density contrast relative to seawater varied within and among
      taxa for fish flesh (0.9919-1.036), squid soft body parts (mantle, arms,
      tentacle, braincase, eyes; 1.009-1.057), and squid hard body parts (beak and pen;
      1.085-1.459). Effects of animal length and environmental conditions on nekton
      density contrast were investigated. The sound speed contrast relative to seawater
      varied within and among taxa for fish flesh (0.986-1.027) and Humboldt squid
      mantle and braincase (0.937-1.028). Material properties in this study are similar
      to values from previous studies on species with similar life histories. In
      general, the sound speed and density of soft body parts of fish and squid were 1%
      3% and 1%-6%, respectively, greater than the surrounding seawater. Hard parts of
      the squid were significantly more dense (6%-46%) than seawater. The material
      properties reported here can be used to improve target strength estimates from
      acoustic scattering models, which could increase the accuracy of biomass
      estimates from acoustic surveys for these nekton. 

PMID- 25994686
TI  - Minke whales (Balaenoptera acutorostrata) respond to navy training.
AB  - Minke whales (Balaenoptera acutorostrata) were acoustically detected and
      localized via their boing calls using 766 h of recorded data from 24 hydrophones
      at the U.S. Navy's Pacific Missile Range Facility located off Kauai, Hawaii. Data
      were collected before, during, and after naval undersea warfare training events,
      which occurred in February over three consecutive years (2011-2013). Data
      collection in the during periods were further categorized as phase A and phase B
      with the latter being the only period with naval surface ship activities (e.g.,
      frigate and destroyer maneuvers including the use of mid-frequency active sonar).
      Minimum minke whale densities were estimated for all data periods based upon the
      numbers of whales acoustically localized within the 3780 km(2) study area. The
      2011 minimum densities in the study area were: 3.64 whales [confidence interval
      (CI) 3.31-4.01] before the training activity, 2.81 whales (CI 2.31-3.42) for
      phase A, 0.69 whales (CI 0.27-1.8) for phase B and 4.44 whales (CI 4.04-4.88)
      after. The minimum densities for the phase B periods were highly statistically
      significantly lower (p < 0.001) from all other periods within each year,
      suggesting a clear response to the phase B training. The phase A period results
      were mixed when compared to other non-training periods. 

PMID- 25994687
TI  - Integration over song classification replicates: song variant analysis in the
      hihi.
AB  - Human expert analyses are commonly used in bioacoustic studies and can
      potentially limit the reproducibility of these results. In this paper, a machine
      learning method is presented to statistically classify avian vocalizations.
      Automated approaches were applied to isolate bird songs from long field
      recordings, assess song similarities, and classify songs into distinct variants.
      Because no positive controls were available to assess the true classification of
      variants, multiple replicates of automatic classification of song variants were
      analyzed to investigate clustering uncertainty. The automatic classifications
      were more similar to the expert classifications than expected by chance.
      Application of these methods demonstrated the presence of discrete song variants
      in an island population of the New Zealand hihi (Notiomystis cincta). The
      geographic patterns of song variation were then revealed by integrating over
      classification replicates. Because this automated approach considers variation in
      song variant classification, it reduces potential human bias and facilitates the
      reproducibility of the results. 

PMID- 25994688
TI  - A multi-hypothesis tracker for clicking whales.
AB  - This paper describes a tracker specially designed to track clicking beaked whales
      using widely spaced bottom-mounted hydrophones, although it can be adapted to
      different species and sensors. The input to the tracker is a sequence of static
      localization solutions obtained using time difference of arrival information at
      widely spaced hydrophones. To effectively handle input localizations with high
      ambiguity, the tracker is based on multi-hypothesis tracker concepts, so it
      considers all potential association hypotheses and keeps a large number of
      potential tracks in memory. The method is demonstrated on actual data and shown
      to successfully track multiple beaked whales at depth. 

PMID- 25994689
TI  - Spatial-temporal ultrasound imaging of residual cavitation bubbles around a fluid
      tissue interface in histotripsy.
AB  - Cavitation is considered as the primary mechanism of soft tissue fragmentation
      (histotripsy) by pulsed high-intensity focused ultrasound. The residual
      cavitation bubbles have a dual influence on the histotripsy pulses: these serve
      as nuclei for easy generation of new cavitation, and act as strong scatterers
      causing energy "shadowing." To monitor the residual cavitation bubbles in
      histotripsy, an ultrafast active cavitation imaging method with relatively high
      signal-to-noise ratio and good spatial-temporal resolution was proposed in this
      paper, which combined plane wave transmission, minimum variance beamforming, and
      coherence factor weighting. The spatial-temporal evolutions of residual
      cavitation bubbles around a fluid-tissue interface in histotripsy under pulse
      duration (PD) of 10-40 MUs and pulse repetition frequency (PRF) of 0.67-2 kHz
      were monitored by this method. The integrated bubble area curves inside the
      tissue interface were acquired from the bubble image sequence, and the formation
      process of histotripsy damage was estimated. It was observed that the histotripsy
      efficiency decreased with both longer PDs and higher PRFs. A direct relationship
      with a coefficient of 1.0365 between histotripsy lesion area and inner residual
      bubble area was found. These results can assist in monitoring and optimization of
      the histotripsy treatment further. 

PMID- 25994690
TI  - Passive acoustic mapping utilizing optimal beamforming in ultrasound therapy
      monitoring.
AB  - Passive acoustic mapping (PAM) is a promising imaging method that enables real
      time three-dimensional monitoring of ultrasound therapy through the
      reconstruction of acoustic emissions passively received on an array of ultrasonic
      sensors. A passive beamforming method is presented that provides greatly improved
      spatial accuracy over the conventionally used time exposure acoustics (TEA) PAM
      reconstruction algorithm. Both the Capon beamformer and the robust Capon
      beamformer (RCB) for PAM are suggested as methods to reduce interference
      artifacts and improve resolution, which has been one of the experimental issues
      previously observed with TEA. Simulation results that replicate the experimental
      artifacts are shown to suggest that bubble interactions are the chief cause.
      Analysis is provided to show that these multiple bubble artifacts are generally
      not reduced by TEA, while Capon-based methods are able to reduce the artifacts.
      This is followed by experimental results from in vitro experiments and in vivo
      oncolytic viral therapy trials that show improved results in PAM, where RCB is
      able to more accurately localize the acoustic activity than TEA. 

PMID- 25994691
TI  - Articulation and vocal tract acoustics at soprano subject's high fundamental
      frequencies.
AB  - The role of the vocal tract for phonation at very high soprano fundamental
      frequencies (F0s) is not yet understood in detail. In this investigation, two
      experiments were carried out with a single professional high soprano subject.
      First, using two dimensional (2D) dynamic real-time magnetic resonance imaging
      (MRI) (24 fps) midsagittal and coronal vocal tract shapes were analyzed while the
      subject sang a scale from Bb5 (932 Hz) to G6 (1568 Hz). In a second experiment,
      volumetric vocal tract MRI data were recorded from sustained phonations (13 s)
      for the pitches C6 (1047 Hz) and G6 (1568 Hz). Formant frequencies were measured
      in physical models created by 3D printing, and calculated from area functions
      obtained from the 3D vocal tract shapes. The data showed that there were only
      minor modifications of the vocal tract shape. These changes involved a decrease
      of the piriform sinus as well as small changes of tongue position. Formant
      frequencies did not exhibit major differences between C6 and G6 for F1 and F3,
      respectively. Only F2 was slightly raised for G6. For G6, however, F2 is not
      excited by any voice source partial. Therefore, this investigation was not able
      to confirm that the analyzed professional soprano subject adjusted formants to
      voice source partials for the analyzed F0s. 

PMID- 25994692
TI  - Community response to noise in Vietnam: exposure-response relationships based on
      the community tolerance level.
AB  - Social surveys on noise annoyance have been conducted in five different cities in
      Vietnam. The surveys included both aircraft noise (three airports) and road
      traffic noise (five cities). The main objective for these studies was to
      establish dose-response functions that were representative for Vietnam. The
      results have been compared with results from similar surveys from other regions.
      Dose-response functions for aircraft noise in Vietnam showing the percentage of
      highly annoyed people versus the noise level are nearly identical to those
      presented in the European Noise Directive [European Commission (2002).
      http://ec.europa.eu/environment/noise/directive.htm]. For road traffic noise,
      however, the results indicate that people in Vietnam are more tolerant. The noise
      levels can be increased by 5-10 dB in order to have a response similar to the
      curve recommended by the European Commission. 

PMID- 25994693
TI  - Low frequency finite element models of the acoustical behavior of earmuffs.
AB  - This paper compares different approaches to model the vibroacoustic behavior of
      earmuffs at low frequency and investigates their accuracy by comparison with
      objective insertion loss measurements recently carried out by Boyer et al.
      [(2014). Appl. Acoust. 83, 76-85]. Two models based on the finite element (FE)
      method where the cushion is either modeled as a spring foundation (SF) or as an
      equivalent solid (ES), and the well-known lumped parameters model (LPM) are
      investigated. Modeling results show that: (i) all modeling strategies are in good
      agreement with measurements, providing that the characterization of the cushion
      equivalent mechanical properties are performed with great care and as close as
      possible to in situ loading, boundary, and environmental conditions and that the
      frequency dependence of the mechanical properties is taken into account, (ii) the
      LPM is the most simple modeling strategy, but the air volume enclosed by the
      earmuff must be correctly estimated, which is not as straightforward as it may
      seem, (iii) similar results are obtained with the SF and the ES FE-models of the
      cushion, but the SF should be preferred to predict the earmuff acoustic response
      at low frequency since it requires less parameters and a less complex
      characterization procedure. 

PMID- 25994694
TI  - Numerical study of interparticle radiation force acting on rigid spheres in a
      standing wave.
AB  - Acoustic radiation force can be used to move micro-sized particles, such as
      cells, in microfluidic devices. Although the number of particles in a
      microfluidic device is large, typically 2.5% (weight/volume), the acoustic force
      acting on a particle is commonly calculated using an analytical formula for a
      single particle in infinite medium. The interparticle forces are typically
      ignored as these are not easily accounted for and calculated with simple closed
      form solutions. Based on the isothermal theory for an ideal fluid, a numerical
      scheme is hereby proposed to calculate the total radiation force, including the
      interparticle forces. The method uses the multipole series expansion and the
      weighted residual method to solve the governing Helmholtz equation with the
      necessary boundary conditions on the particle surface. The effect of different
      parameters on the primary and interparticle forces is studied using the proposed
      numerical scheme. It is shown that, near the pressure node, the interparticle
      forces are dominant and configurations of the spheres are determined by the
      interparticle forces. The proposed numerical scheme can be used for various sizes
      of spherical particles. 

PMID- 25994695
TI  - Mathematical models for the acoustic response of a solids-loaded encapsulated
      bubble.
AB  - A method of active acoustic resonance interference spectroscopy is introduced for
      estimation of bubble properties. A modified form of Rayleigh-Plesset equation for
      forced oscillation of either a single free bubble or elastic shell encapsulated
      microbubble with attached solids loading is solved by the regular perturbation
      method for steady oscillatory solutions as a result of small amplitude acoustic
      excitation by a point sinusoidal oscillator. A model for the total pressure field
      at an acoustic receiver in an incompressible liquid is then solved by the regular
      perturbation method. Closed-form analytical solutions are found for pressure
      power at the acoustic receiver as a function of the excitation frequency and
      strength; the properties of the bubble, liquid, and encapsulating shell; and the
      geometry of the active monitoring system. The receiver pressure power exhibits a
      maximum due to bubble resonance and a minimum due to destructive interference
      between source and bubble response pressure fields at higher excitation
      frequencies. The inverse problem is solved to derive unique closed-form
      analytical estimators for bubble equilibrium size, attached solids mass loading,
      and encapsulating layer dilatational viscosity as a function of the frequencies
      of the fundamental resonance maximum, interference minimum, second harmonic
      maximum total average acoustic power, monitoring system, and phase properties. 

PMID- 25994696
TI  - Two types of nonlinear wave equations for diffractive beams in bubbly liquids
      with nonuniform bubble number density.
AB  - This paper theoretically treats the weakly nonlinear propagation of diffracted
      sound beams in nonuniform bubbly liquids. The spatial distribution of the number
      density of the bubbles, initially in a quiescent state, is assumed to be a slowly
      varying function of the spatial coordinates; the amplitude of variation is
      assumed to be small compared to the mean number density. A previous derivation
      method of nonlinear wave equations for plane progressive waves in uniform bubbly
      liquids [Kanagawa, Yano, Watanabe, and Fujikawa (2010). J. Fluid Sci. Technol.
      5(3), 351-369] is extended to handle quasi-plane beams in weakly nonuniform
      bubbly liquids. The diffraction effect is incorporated by adding a relation that
      scales the circular sound source diameter to the wavelength into the original set
      of scaling relations composed of nondimensional physical parameters. A set of
      basic equations for bubbly flows is composed of the averaged equations of mass
      and momentum, the Keller equation for bubble wall, and supplementary equations.
      As a result, two types of evolution equations, a nonlinear Schrodinger equation
      including dissipation, diffraction, and nonuniform effects for high-frequency
      short-wavelength case, and a Khokhlov-Zabolotskaya-Kuznetsov equation including
      dispersion and nonuniform effects for low-frequency long-wavelength case, are
      derived from the basic set. 

PMID- 25994697
TI  - Far-field scattering model for wave propagation in random media.
AB  - A simple approximate model is developed for ultrasonic wave propagation in a
      random elastic medium. The model includes second order multiple scattering and is
      applicable in all frequency ranges including geometric. It is based on the far
      field approximation of the reference medium Green's function and simplifications
      of the mass operator in addition to those of the first smooth approximation. In
      this approximation, the dispersion equation for the perturbed wave number is
      obtained; its solution yields the dispersive ultrasonic velocity and attenuation
      coefficients. The approximate solution is general and is suitable for nonequiaxed
      grains with arbitrary elastic symmetry. For equiaxed cubic grains, the solution
      is compared with the existing second order models and with the Born
      approximation. The comparison shows that the obtained solution has smaller error
      than the Born approximation and shows reasonably well the onset of multiple
      scattering and the applicability limit of the Born approximation at high
      frequency. The perturbed wave number in the developed model does not depend
      explicitly on the crystallite elastic properties even for arbitrary
      crystallographic symmetry; it depends on two nondimensional scattering elastic
      parameters and the macroscopic ultrasonic velocity (those are dependent on the
      crystallite moduli). This provides an advantage for potential schemes for
      inversion from attenuation to material microstructure. 

PMID- 25994698
TI  - Infrasonic wind noise under a deciduous tree canopy.
AB  - In a recent paper, the infrasonic wind noise measured at the floor of a pine
      forest was predicted from the measured wind velocity spectrum and profile within
      and above the trees [Raspet and Webster, J. Acoust. Soc. Am. 137, 651-659
      (2015)]. This research studies the measured and predicted wind noise under a
      deciduous forest with and without leaves. A calculation of the turbulence-shear
      interaction pressures above the canopy predicts the low frequency peak in the
      wind noise spectrum. The calculated turbulence-turbulence interaction pressure
      due to the turbulence field near the ground predicts the measured wind noise
      spectrum in the higher frequency region. The low frequency peak displays little
      dependence on whether the trees have leaves or not. The high frequency
      contribution with leaves is approximately an order of magnitude smaller than the
      contribution without leaves. Wind noise levels with leaves are very similar to
      the wind noise levels in the pine forest. The calculated turbulence-shear
      contribution from the wind within the canopy is shown to be negligible in
      comparison to the turbulence-turbulence contribution in both cases. In addition,
      the effect of taller forests and smaller roughness lengths than those of the test
      forest on the turbulence-shear interaction is simulated based on measured
      meteorological parameters. 

PMID- 25994699
TI  - Sound source identification and sound radiation modeling in a moving medium using
      the time-domain equivalent source method.
AB  - Planar near-field acoustic holography has been successfully extended to
      reconstruct the sound field in a moving medium, however, the reconstructed field
      still contains the convection effect that might lead to the wrong identification
      of sound sources. In order to accurately identify sound sources in a moving
      medium, a time-domain equivalent source method is developed. In the method, the
      real source is replaced by a series of time-domain equivalent sources whose
      strengths are solved iteratively by utilizing the measured pressure and the known
      convective time-domain Green's function, and time averaging is used to reduce the
      instability in the iterative solving process. Since these solved equivalent
      source strengths are independent of the convection effect, they can be used not
      only to identify sound sources but also to model sound radiations in both moving
      and static media. Numerical simulations are performed to investigate the
      influence of noise on the solved equivalent source strengths and the effect of
      time averaging on reducing the instability, and to demonstrate the advantages of
      the proposed method on the source identification and sound radiation modeling. 

PMID- 25994700
TI  - The role of excitation-pattern cues in the detection of frequency shifts in
      bandpass-filtered complex tones.
AB  - One task intended to measure sensitivity to temporal fine structure (TFS)
      involves the discrimination of a harmonic complex tone from a tone in which all
      harmonics are shifted upwards by the same amount in hertz. Both tones are passed
      through a fixed bandpass filter centered on the high harmonics to reduce the
      availability of excitation-pattern cues and a background noise is used to mask
      combination tones. The role of frequency selectivity in this "TFS1" task was
      investigated by varying level. Experiment 1 showed that listeners performed more
      poorly at a high level than at a low level. Experiment 2 included intermediate
      levels and showed that performance deteriorated for levels above about 57 dB
      sound pressure level. Experiment 3 estimated the magnitude of excitation-pattern
      cues from the variation in forward masking of a pure tone as a function of
      frequency shift in the complex tones. There was negligible variation, except for
      the lowest level used. The results indicate that the changes in excitation level
      at threshold for the TFS1 task would be too small to be usable. The results are
      consistent with the TFS1 task being performed using TFS cues, and with frequency
      selectivity having an indirect effect on performance via its influence on TFS
      cues. 

PMID- 25994701
TI  - Human middle-ear model with compound eardrum and airway branching in mastoid air
      cells.
AB  - An acoustical/mechanical model of normal adult human middle-ear function is
      described for forward and reverse transmission. The eardrum model included one
      component bound along the manubrium and another bound by the tympanic cleft.
      Eardrum components were coupled by a time-delayed impedance. The acoustics of the
      middle-ear cleft was represented by an acoustical transmission-line model for the
      tympanic cavity, aditus, antrum, and mastoid air cell system with variable
      amounts of excess viscothermal loss. Model parameters were fitted to published
      measurements of energy reflectance (0.25-13 kHz), equivalent input impedance at
      the eardrum (0.25-11 kHz), temporal-bone pressure in scala vestibuli and scala
      tympani (0.1-11 kHz), and reverse middle-ear impedance (0.25-8 kHz). Inner-ear
      fluid motion included cochlear and physiological third-window pathways. The two
      component eardrum with time delay helped fit intracochlear pressure responses. A
      multi-modal representation of the eardrum and high-frequency modeling of the
      middle-ear cleft helped fit ear-canal responses. Input reactance at the eardrum
      was small at high frequencies due to multiple modal resonances. The model
      predicted the middle-ear efficiency between ear canal and cochlea, and the
      cochlear pressures at threshold. 

PMID- 25994702
TI  - Informational masking of monaural target speech by a single contralateral
      formant.
AB  - Recent research suggests that the ability of an extraneous formant to impair
      intelligibility depends on the variation of its frequency contour. This idea was
      explored using a method that ensures interference cannot occur through energetic
      masking. Three-formant (F1 + F2 + F3) analogues of natural sentences were
      synthesized using a monotonous periodic source. Target formants were presented
      monaurally, with the target ear assigned randomly on each trial. A competitor for
      F2 (F2C) was presented contralaterally; listeners must reject F2C to optimize
      recognition. In experiment 1, F2Cs with various frequency and amplitude contours
      were used. F2Cs with time-varying frequency contours were effective competitors;
      constant-frequency F2Cs had far less impact. To a lesser extent, amplitude
      contour also influenced competitor impact; this effect was additive. In
      experiment 2, F2Cs were created by inverting the F2 frequency contour about its
      geometric mean and varying its depth of variation over a range from constant to
      twice the original (0%-200%). The impact on intelligibility was least for
      constant F2Cs and increased up to ~100% depth, but little thereafter. The effect
      of an extraneous formant depends primarily on its frequency contour; interference
      increases as the depth of variation is increased until the range exceeds that
      typical for F2 in natural speech. 

PMID- 25994704
TI  - Information-theoretic analysis of iterated Bayesian acoustic source localization
      in a static ocean waveguide.
AB  - Fundamental constructs of information theory are applied to quantify the
      performance of iterated (sequential) Bayesian localization of a time-harmonic
      source in a range- and time-invariant acoustic waveguide using the segmented
      Fourier transforms of the received pressure time series. The nonlinear relation,
      defined by acoustic propagation, between the source location and the received
      narrowband spectral components is treated as a nonlinear communication channel.
      The performance analysis includes mismatch between the acoustic channel and the
      model channel on which the Bayesian inference is based. Source location
      uncertainty is quantified by the posterior probability density of source
      location, by the posterior entropy and associated uncertainty area, by the
      information gain (relative entropy) at each iteration, and by large-ensemble
      limits of these quantities. A computational example for a vertical receiver array
      in a shallow-water waveguide is presented with acoustic propagation represented
      by normal modes and ambient noise represented by a Kuperman-Ingenito model.
      Performance degradation due to noise-model mismatch is quantified in an example.
      Potential extensions to uncertain and stochastic environments are discussed. 

PMID- 25994703
TI  - Changes in otoacoustic emissions during selective auditory and visual attention.
AB  - Previous studies have demonstrated that the otoacoustic emissions (OAEs) measured
      during behavioral tasks can have different magnitudes when subjects are attending
      selectively or not attending. The implication is that the cognitive and
      perceptual demands of a task can affect the first neural stage of auditory
      processing-the sensory receptors themselves. However, the directions of the
      reported attentional effects have been inconsistent, the magnitudes of the
      observed differences typically have been small, and comparisons across studies
      have been made difficult by significant procedural differences. In this study, a
      nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was
      used to measure cochlear responses from human subjects while they simultaneously
      performed behavioral tasks requiring selective auditory attention (dichotic or
      diotic listening), selective visual attention, or relative inattention. Within
      subjects, the differences in nSFOAE magnitude between inattention and attention
      conditions were about 2-3 dB for both auditory and visual modalities, and the
      effect sizes for the differences typically were large for both nSFOAE magnitude
      and phase. These results reveal that the cochlear efferent reflex is
      differentially active during selective attention and inattention, for both
      auditory and visual tasks, although they do not reveal how attention is improved
      when efferent activity is greater. 

PMID- 25994705
TI  - Time domain compressive beam forming of ultrasound signals.
AB  - Ultrasound imaging is a wide spread technique used in medical imaging as well as
      in non-destructive testing. The technique offers many advantages such as real
      time imaging, good resolution, prompt acquisition, ease of use, and low cost
      compared to other techniques such as x-ray imaging. However, the maximum frame
      rate achievable is limited as several beams must be emitted to compute a single
      image. For each emitted beam, one must wait for the wave to propagate back and
      forth, thus imposing a limit to the frame rate. Several attempts have been made
      to use less beams while maintaining image quality. Although efficiently
      increasing the frame rate, these techniques still use several transmit beams.
      Compressive Sensing (CS), a universal data completion scheme based on convex
      optimization, has been successfully applied to a number of imaging modalities
      over the past few years. Using a priori knowledge of the signal, it can compute
      an image using less data allowing for shorter acquisition times. In this paper,
      it is shown that a valid CS framework can be derived from ultrasound propagation
      theory, and that this framework can be used to compute images of scatterers using
      only one plane wave as a transmit beam. 

PMID- 25994706
TI  - A sidelobe suppressing near-field beamforming approach for ultrasound array
      imaging.
AB  - A method is proposed to suppress sidelobe level for near-field beamforming in
      ultrasound array imaging. An optimization problem is established, and the second
      order cone algorithm is used to solve the problem to obtain the weight vector
      based on the near-field response vector of a transducer array. The weight vector
      calculation results show that the proposed method can be used to suppress the
      sidelobe level of the near-field beam pattern of a transducer array. Ultrasound
      images following the application of weight vector to the array of a wire phantom
      are obtained by simulation with the Field II program, and the images of a wire
      phantom and anechoic sphere phantom are obtained experimentally with a 64-element
      26 MHz linear phased array. The experimental and simulation results agree well
      and show that the proposed method can achieve a much lower sidelobe level than
      the conventional delay and sum beamforming method. The wire phantom image is
      demonstrated to focus much better and the contrast of the anechoic sphere phantom
      image improved by applying the proposed beamforming method. 

PMID- 25994707
TI  - Effects of real-time cochlear implant simulation on speech production.
AB  - Investigations using normal-hearing subjects listening to simulations of cochlear
      implant (CI) acoustic processing have provided substantial information about the
      impact of these distorted listening conditions on the accuracy of auditory
      perception, but extensions of this method to the domain of speech production have
      been limited. In the present study, a portable, real-time vocoder was used to
      simulate conditions of CI auditory feedback during speech production in NH
      subjects. Acoustic-phonetic characteristics of sibilant fricatives, aspirated
      stops, and F1/F2 vowel qualities were analyzed for changes as a result of CI
      simulation of acoustic speech feedback. Significant changes specific to F1 were
      observed; speakers reduced their phonological vowel height contrast, typically
      via talker-specific raising of the low vowels [ae] and [alpha] or lowering of
      high vowels [i] and [u]. Comparisons to the results of both localized feedback
      perturbation procedures and investigations of speech production in deaf adults
      with CIs are discussed. 

PMID- 25994708
TI  - Effect of the division between early and late reflections on intelligibility of
      ideal binary-masked speech.
AB  - The ideal binary mask (IBM) that was originally defined in anechoic conditions
      has been found to yield substantial improvements in speech intelligibility in
      noise. The IBM has recently been extended to reverberant conditions where the
      direct sound and early reflections of target speech are regarded as the desired
      signal. It is of great interest to know how the division between early and late
      reflections impacts on the intelligibility of the IBM-processed noisy reverberant
      speech. In this present study, the division between early and late reflections in
      three rooms was first determined by four typical estimation approaches and then
      used to compute the IBMs in reverberant conditions. The IBMs were then applied to
      the noisy reverberant mixture signal for segregating the desired signal, and the
      segregated signal was further presented to normal-hearing listeners for word
      recognition. Results showed that the IBMs with different divisions between early
      and late reflections provided substantial improvements in speech intelligibility
      over the unprocessed mixture signals in all conditions tested, and there were
      small, but statistically significant, differences in speech intelligibility
      between the different IBMs in some conditions tested. 

PMID- 25994709
TI  - Speech perception of sine-wave signals by children with cochlear implants.
AB  - Children need to discover linguistically meaningful structures in the acoustic
      speech signal. Being attentive to recurring, time-varying formant patterns helps
      in that process. However, that kind of acoustic structure may not be available to
      children with cochlear implants (CIs), thus hindering development. The major goal
      of this study was to examine whether children with CIs are as sensitive to time
      varying formant structure as children with normal hearing (NH) by asking them to
      recognize sine-wave speech. The same materials were presented as speech in noise,
      as well, to evaluate whether any group differences might simply reflect general
      perceptual deficits on the part of children with CIs. Vocabulary knowledge,
      phonemic awareness, and "top-down" language effects were all also assessed.
      Finally, treatment factors were examined as possible predictors of outcomes.
      Results showed that children with CIs were as accurate as children with NH at
      recognizing sine-wave speech, but poorer at recognizing speech in noise. Phonemic
      awareness was related to that recognition. Top-down effects were similar across
      groups. Having had a period of bimodal stimulation near the time of receiving a
      first CI facilitated these effects. Results suggest that children with CIs have
      access to the important time-varying structure of vocal-tract formants. 

PMID- 25994710
TI  - Expectations and speech intelligibility.
AB  - Socio-indexical cues and paralinguistic information are often beneficial to
      speech processing as this information assists listeners in parsing the speech
      stream. Associations that particular populations speak in a certain speech style
      can, however, make it such that socio-indexical cues have a cost. In this study,
      native speakers of Canadian English who identify as Chinese Canadian and White
      Canadian read sentences that were presented to listeners in noise. Half of the
      sentences were presented with a visual-prime in the form of a photo of the
      speaker and half were presented in control trials with fixation crosses.
      Sentences produced by Chinese Canadians showed an intelligibility cost in the
      face-prime condition, whereas sentences produced by White Canadians did not. In
      an accentedness rating task, listeners rated White Canadians as less accented in
      the face-prime trials, but Chinese Canadians showed no such change in perceived
      accentedness. These results suggest a misalignment between an expected and an
      observed speech signal for the face-prime trials, which indicates that social
      information about a speaker can trigger linguistic associations that come with
      processing benefits and costs. 

PMID- 25994711
TI  - Speech timing and linguistic rhythm: on the acoustic bases of rhythm typologies.
AB  - Research into linguistic rhythm has been dominated by the idea that languages can
      be classified according to rhythmic templates, amenable to assessment by acoustic
      measures of vowel and consonant durations. This study tested predictions of two
      proposals explaining the bases of rhythmic typologies: the Rhythm Class
      Hypothesis which assumes that the templates arise from an extensive vs a limited
      use of durational contrasts, and the Control and Compensation Hypothesis which
      proposes that the templates are rooted in more vs less flexible speech production
      strategies. Temporal properties of segments, syllables and rhythmic feet were
      examined in two accents of British English, a "stress-timed" variety from Leeds,
      and a "syllable-timed" variety spoken by Panjabi-English bilinguals from
      Bradford. Rhythm metrics were calculated. A perception study confirmed that the
      speakers of the two varieties differed in their perceived rhythm. The results
      revealed that both typologies were informative in that to a certain degree, they
      predicted temporal patterns of the two varieties. None of the metrics tested was
      capable of adequately reflecting the temporal complexity found in the durational
      data. These findings contribute to the critical evaluation of the explanatory
      adequacy of rhythm metrics. Acoustic bases and limitations of the traditional
      rhythmic typologies are discussed. 

PMID- 25994712
TI  - Effects of contextual cues on speech recognition in simulated electric-acoustic
      stimulation.
AB  - Low-frequency acoustic cues have shown to improve speech perception in cochlear
      implant listeners. However, the mechanisms underlying this benefit are still not
      well understood. This study investigated the extent to which low-frequency cues
      can facilitate listeners' use of linguistic knowledge in simulated electric
      acoustic stimulation (EAS). Experiment 1 examined differences in the magnitude of
      EAS benefit at the phoneme, word, and sentence levels. Speech materials were
      processed via noise-channel vocoding and lowpass (LP) filtering. The amount of
      spectral degradation in the vocoder speech was varied by applying different
      numbers of vocoder channels. Normal-hearing listeners were tested on vocoder
      alone, LP-alone, and vocoder + LP conditions. Experiment 2 further examined
      factors that underlie the context effect on EAS benefit at the sentence level by
      limiting the low-frequency cues to temporal envelope and periodicity (AM + FM).
      Results showed that EAS benefit was greater for higher-context than for lower
      context speech materials even when the LP ear received only low-frequency AM + FM
      cues. Possible explanations for the greater EAS benefit observed with higher
      context materials may lie in the interplay between perceptual and expectation
      driven processes for EAS speech recognition, and/or the band-importance functions
      for different types of speech materials. 

PMID- 25994713
TI  - An ultrasound study of Canadian French rhotic vowels with polar smoothing spline
      comparisons.
AB  - This is an acoustic and articulatory study of Canadian French rhotic vowels,
      i.e., mid front rounded vowels /o oe oe/ produced with a rhotic perceptual
      quality, much like English [?] or [r], leading heureux, commun, and docteur to
      sound like [???], [kom?], and [doktar?]. Ultrasound, video, and acoustic data
      from 23 Canadian French speakers are analyzed using several measures of mid
      sagittal tongue contours, showing that the low F3 of rhotic vowels is achieved
      using bunched and retroflex tongue postures and that the articulatory-acoustic
      mapping of F1 and F2 are rearranged in systems with rhotic vowels. A subset of
      speakers' French vowels are compared with their English [r]/[?], revealing that
      the French vowels are consistently less extreme in low F3 and its articulatory
      correlates, even for the most rhotic speakers. Polar coordinates are proposed as
      a replacement for Cartesian coordinates in calculating smoothing spline
      comparisons of mid-sagittal tongue shapes, because they enable comparisons to be
      roughly perpendicular to the tongue surface, which is critical for comparisons
      involving tongue root position but appropriate for all comparisons involving mid
      sagittal tongue contours. 

PMID- 25994714
TI  - The role of spectral cues in timbre discrimination by ferrets and humans.
AB  - Timbre distinguishes sounds of equal loudness, pitch, and duration; however,
      little is known about the neural mechanisms underlying timbre perception. Such
      understanding requires animal models such as the ferret in which neuronal and
      behavioral observation can be combined. The current study asked what spectral
      cues ferrets use to discriminate between synthetic vowels. Ferrets were trained
      to discriminate vowels differing in the position of the first (F1) and second
      formants (F2), inter-formant distance, and spectral centroid. In experiment 1,
      ferrets responded to probe trials containing novel vowels in which the spectral
      cues of trained vowels were mismatched. Regression models fitted to behavioral
      responses determined that F2 and spectral centroid were stronger predictors of
      ferrets' behavior than either F1 or inter-formant distance. Experiment 2 examined
      responses to single formant vowels and found that individual spectral peaks
      failed to account for multi-formant vowel perception. Experiment 3 measured
      responses to unvoiced vowels and showed that ferrets could generalize vowel
      identity across voicing conditions. Experiment 4 employed the same design as
      experiment 1 but with human participants. Their responses were also predicted by
      F2 and spectral centroid. Together these findings further support the ferret as a
      model for studying the neural processes underlying timbre perception. 

PMID- 25994715
TI  - The early maximum likelihood estimation model of audiovisual integration in
      speech perception.
AB  - Speech perception is facilitated by seeing the articulatory mouth movements of
      the talker. This is due to perceptual audiovisual integration, which also causes
      the McGurk-MacDonald illusion, and for which a comprehensive computational
      account is still lacking. Decades of research have largely focused on the fuzzy
      logical model of perception (FLMP), which provides excellent fits to experimental
      observations but also has been criticized for being too flexible, post hoc and
      difficult to interpret. The current study introduces the early maximum likelihood
      estimation (MLE) model of audiovisual integration to speech perception along with
      three model variations. In early MLE, integration is based on a continuous
      internal representation before categorization, which can make the model more
      parsimonious by imposing constraints that reflect experimental designs. The study
      also shows that cross-validation can evaluate models of audiovisual integration
      based on typical data sets taking both goodness-of-fit and model flexibility into
      account. All models were tested on a published data set previously used for
      testing the FLMP. Cross-validation favored the early MLE while more conventional
      error measures favored more complex models. This difference between conventional
      error measures and cross-validation was found to be indicative of over-fitting in
      more complex models such as the FLMP. 

PMID- 25994716
TI  - Invariance in vowel systems.
AB  - This study applies information geometry of normal distribution to model Japanese
      vowels on the basis of the first and second formants. The distribution of
      Kullback-Leibler (KL) divergence and its decomposed components were investigated
      to reveal the statistical invariance in the vowel system. The results suggest
      that although significant variability exists in individual KL divergence
      distributions, the population distribution tends to converge into a specific log
      normal distribution. This distribution can be considered as an invariant
      distribution for the standard-Japanese speaking population. Furthermore, it was
      revealed that the mean and variance components of KL divergence are linearly
      related in the population distribution. The significance of these invariant
      features is discussed. 

PMID- 25994717
TI  - Ground cross-modal impedance as a tool for analyzing ground/plate interaction and
      ground wave propagation.
AB  - An analytical approach is investigated to model ground-plate interaction based on
      modal decomposition and the two-dimensional Fourier transform. A finite
      rectangular plate subjected to flexural vibration is coupled with the ground and
      modeled with the Kirchhoff hypothesis. A Navier equation represents the
      stratified ground, assumed infinite in the x- and y-directions and free at the
      top surface. To obtain an analytical solution, modal decomposition is applied to
      the structure and a Fourier Transform is applied to the ground. The result is a
      new tool for analyzing ground-plate interaction to resolve this problem: ground
      cross-modal impedance. It allows quantifying the added-stiffness, added-mass, and
      added-damping from the ground to the structure. Similarity with the parallel
      acoustic problem is highlighted. A comparison between the theory and the
      experiment shows good matching. Finally, specific cases are investigated, notably
      the influence of layer depth on plate vibration. 

PMID- 25994718
TI  - Underwater sound radiation from an elastically coated plate with an embedded and
      distributed inhomogeneity.
AB  - This paper studies the effects of an embedded and distributed inhomogeneity on
      the underwater sound radiation from an elastically coated plate. Embedding a
      signal conditioning plate (SCP) in the coating material provides an extra
      parameter for controlling the sound radiation of the plate, as compared with the
      previous design with an SCP on the coating surface [Y. Zhang and J. Pan, J.
      Acoust. Soc. Am. 133(1), 173-185 (2013)]. For such a configuration, the vibration
      and sound responses of the coated plate to a point force excitation are described
      by three coupled Fredholm integral equations of the second kind. Its acoustical
      properties are examined by comparing the radiation powers from plates without an
      SCP, with a surface SCP, and with an embedded SCP. The differences in the sound
      powers are explained through resonance and scattering caused by the interaction
      of the embedded SCP with structural waves. The effects of the depth of the
      embedded SCP in the coating material on the sound radiation properties of the
      plate are discussed in detail. 

PMID- 25994719
TI  - Free and forced vibrations of hollow elastic cylinders of finite length.
AB  - An analytical model of axisymmetric vibrations of hollow elastic circular
      cylinders with arbitrary boundary conditions is presented. Free vibrations of
      cylinders with free or fixed boundaries and forced vibrations of cylinders with
      specified non-uniform displacement or stress on the boundaries are considered.
      Three series solutions are used and each term in each series is an exact solution
      to the exact governing equations of motion. The terms in the expressions for
      components of displacement and stress are products of Bessel and sinusoidal
      functions and are orthogonal to each other. Complete sets of functions in the
      radial and axial directions are formed by terms in the first series and the other
      two, respectively. It is therefore possible to satisfy arbitrary boundary
      conditions. It is shown that just two terms in each series are sufficient to
      determine several resonance frequencies of cylinders with certain specified
      boundary conditions. The error is less than 1%. Numerical results are also
      presented for forced vibration of hollow steel cylinders of length 10 mm and
      outer diameter 10 mm with specified normal displacement or stress. Excellent
      agreement with finite element results is obtained at all frequencies up to 1 MHz.
      Convergence of the series is also discussed. 

PMID- 25994720
TI  - Dynamics of soundscape in a shallow water marine environment: a study of the
      habitat of the Indo-Pacific humpback dolphin.
AB  - The underwater acoustic field is an important ecological element for many aquatic
      animals. This research examines the soundscape of a critically endangered Indo
      Pacific humpback dolphin population in the shallow water environment off the west
      coast of Taiwan. Underwater acoustic recordings were conducted between late
      spring and late fall in 2012 at Yunlin (YL), which is close to a shipping lane,
      and Waisanding (WS), which is relatively pristine. Site-specific analyses were
      performed on the dynamics of the temporal and spectral acoustic characteristics
      for both locations. The results highlight the dynamics of the soundscape in two
      major octave bands: 150-300 Hz and 1.2-2.4 kHz. The acoustic energy in the former
      frequency band is mainly associated with passing container vessels near YL, while
      the latter frequency band is from sonic fish chorus at nighttime in both
      recording sites. In addition, large variation of low frequency acoustic energy
      throughout the study period was noticed at WS, where the water depths ranged
      between 1.5 and 4.5 m depending on tidal cycle. This phenomenon suggests that
      besides certain sound sources in the environment, the coastal soundscape may also
      be influenced by its local bathymetry and the dynamics of the physical
      environment. 

PMID- 25994721
TI  - High-frequency normal-mode statistics in shallow water: the combined effect of
      random surface and internal waves.
AB  - In an earlier article, the statistical properties of mode propagation were
      studied at a frequency of 1 kHz in a shallow water environment with random sound
      speed perturbations from linear internal waves, using a hybrid transport theory
      and Monte Carlo numerical simulations. Here, the analysis is extended to include
      the effects of random linear surface waves, in isolation and in combination with
      internal waves. Mode coupling rates for both surface and internal waves are found
      to be significant, but strongly dependent on mode number. Mode phase
      randomization by surface waves is found to be dominated by coupling effects, and
      therefore a full transport theory treatment of the range evolution of the cross
      mode coherence matrix is needed. The second-moment of mode amplitudes is
      calculated using transport theory, thereby providing the mean intensity while the
      fourth-moment is calculated using Monte Carlo simulations, which provides the
      scintillation index. The transport theory results for second-moment statistics
      are shown to closely reproduce Monte Carlo simulations. Both surface waves and
      internal waves strongly influence the acoustic field fluctuations. 

PMID- 25994722
TI  - Comment on "Attenuation and dispersion of sound in dilute suspensions of
      spherical particles" [J. Acoust. Soc. Am. 108(1), 126-146 (2000)].
AB  - Comment is made on an article by Temkin [J. Acoust. Soc. Am. 108(1), 126-146
      (2000)]. This work illustrates the impact of particle size distribution on the
      dispersion and attenuation of sound waves propagating through particle
      suspensions. Temkin's propagation theory is extended for poly-disperse
      distributions of spherical particles, applicable to real suspensions. Significant
      changes in dispersion and attenuation appear near the particle resonance for both
      bubble and solid particle suspensions. Existing experimental data for bubble
      distributions also shows a good agreement with the poly-disperse modifications
      proposed. 

PMID- 25994723
TI  - Comment on "Transient response of an acoustic medium by an excited submerged
      spherical shell" [J. Acoust. Soc. Am. 109(6), 2789-2796 (2001)].
AB  - A closed form solution was derived previously for the response of a submerged
      spherical shell when the shell was excited by a spatially distributed, transient
      load at its inner surface [Zakout (2001). J. Acoust. Soc. Am. 109(6), 2789-2796].
      Numerical results were presented for the modal and total acoustic pressures
      outside the empty sphere when the load's temporal history corresponded to the
      Heaviside step function. However, the result presented for the shell's
      "breathing" mode was inconsistent with these data as it corresponded to the delta
      Dirac (impulse) function. Furthermore, numerical results, which were given later
      for the total acoustic pressure responses, did not involve either of these
      excitations. Consequently the present objective is to rectify these anomalies. 

PMID- 25994724
TI  - Smoothness of an equation for the glottal flow rate versus the glottal area.
AB  - This letter proposes a correction to an equation by Titze [J. Acoust. Soc. Am.
      75, 570-580 (1984)] for the volume velocity of the glottal air flow given the
      glottal area and other laryngeal parameters. It shows that the equation produces
      non-differentiable waveforms at the instants of glottal closure and opening, if
      the glottal area is also not differentiable at those instants. By adding an air
      viscosity term to the equation, twice-differentiability is obtained. Also, the
      letter corrects a sign error in the original formulation. 

PMID- 25994725
TI  - Self-synchronization and spatial diversity of passive time reversal
      communication.
AB  - Time reversal (TR) achieves spatial and temporal focusing in complex
      environments. In the context of communications, passive (uplink) TR is equivalent
      to active (downlink) TR with the communications link being in opposite directions
      but with the same theoretical performance. The benefit of passive TR, however, is
      its natural self-synchronization, making TR communications robust and readily
      extended to cases involving temporal diversity and synthetic aperture
      communications. Self-synchronization is examined analytically and demonstrated
      with shallow water experimental data. In addition, the impact of spatial
      diversity on communications performance is investigated in terms of the aperture
      and element spacing of the 64-element vertical receive array. 

PMID- 25994726
TI  - Experimental evidence of modal wavenumber relation to zeros in the wavenumber
      spectrum of a simply supported plate.
AB  - The modal wavenumber of rectangular, simply supported, isotropic thin plates was
      theoretically shown to be related to the zeros in the wavenumber spectrum and not
      to the peaks, resulting in an error between the actual modal wavenumber and
      location of the wavenumber spectrum peak for low mode orders. This theoretical
      proof is confirmed by experimental results reported in this letter. 

PMID- 25994727
TI  - Efficient modeling of range-dependent ray convergence effects in propagation and
      reverberation.
AB  - In an earlier paper [Harrison (2013). J. Acoust. Soc. Am. 133, 3777-3789] the
      computationally efficient energy flux approach to modeling sound propagation was
      modified to include focusing, ray convergence, and caustic-like behavior. The
      derivation started with the coherent normal mode sum but retained only terms that
      interfered on a scale of a ray cycle distance. Here, by starting with the
      adiabatic mode sum, the formulation is extended to a slowly varying range
      dependent environment and applied to the target-echo and reverberation model,
      Artemis. Some examples are given. 

PMID- 25994728
TI  - Erratum: Data-based matched-mode source localization for a moving source [J.
      Acoust. Soc. Am. 135, 1218-1230 (2014)].

PMID- 25994729
TI  - Erratum: Influence of the stimulus presentation rate on medial olivocochlear
      system assays [J. Acoust. Soc. Am. 137(2), 724-732 (2015)].

PMID- 25994733
TI  - Layer filtering for seafloor scatterers imaging.
AB  - The image source method in acoustics is well known to simulate reverberation. It
      has also been recently used for characterization of seafloor sound-speed
      structure. The idea is to detect image sources by imaging techniques to obtain
      information about the environment. In this paper, the idea is to use the
      detection of image sources to remove reflections from plane interfaces in
      recorded signals and perform imaging with this filtered signal. This imaging
      process highlights scatterers because their wave front shapes are different than
      those from plane interfaces. Applications can be in seafloor buried object
      detection or scattering analysis from interface roughnesses or volume
      heterogeneities. 

PMID- 25994732
TI  - Toward a consensus on symbolic notation of harmonics, resonances, and formants in
      vocalization.

PMID- 25994734
TI  - Biomimetic direction of arrival estimation for resolving front-back confusions in
      hearing aids.
AB  - Sound sources at the same angle in front or behind a two-microphone array (e.g.,
      bilateral hearing aids) produce the same time delay and two estimates for the
      direction of arrival: A front-back confusion. The auditory system can resolve
      this issue using head movements. To resolve front-back confusion for hearing-aid
      algorithms, head movement was measured using an inertial sensor. Successive time
      delay estimates between the microphones are shifted clockwise and
      counterclockwise by the head movement between estimates and aggregated in two
      histograms. The histogram with the largest peak after multiple estimates
      predicted the correct hemifield for the source, eliminating the front-back
      confusions. 

PMID- 25994735
TI  - Acoustic Rayleigh scattering in water-saturated granular medium with
      quasicrystalline approximation.
AB  - A closed-form solution for the effective wavenumber in a water-saturated medium
      as a function of the Rayleigh parameter is derived up to the second leading terms
      in the real part and first leading term in the imaginary part. This is based on
      the Waterman multiple scattering formulation with the quasicrystalline
      approximation (QCA) and the Percus-Yevick pair-correlation function. The
      formula's resultant sound speed and attenuation are compared to the regression
      relation matching the measurements in the Rayleigh scattering region [Kimura, J.
      Acoust. Soc. Am. 129(6), 3544-3561 (2011)]. The sound speeds are comparable.
      However, for the attenuation, it is shown that the QCA result underestimates the
      measured attenuation while its behavior exhibits similar frequency dependency of
      f(4). 

PMID- 25994736
TI  - Spectral overlap and interaural time difference sensitivity: possible role of
      binaural interference.
AB  - A follow-up experiment to those conducted by Brown and Yost [(2011). J. Acoust.
      Soc. Am. 130, 358-364; (2013). Basic Aspects of Hearing: Physiology and
      Perception (Springer, London, UK)] examined interaural time difference (ITD)
      discrimination for a low-frequency target noise band flanked by monotic noise
      bands that were either lower-frequency than the target band, higher-frequency, or
      both. The flanking bands were either spectrally contiguous with the target band
      or spectrally separated. Significant interference in ITD processing occurred in
      the presence of the high-frequency flanking band. Results are discussed by way of
      a comparison of the conditions in the present study to those in studies of
      binaural interference. The possible role of attention is also discussed. 

PMID- 25994737
TI  - Fine-resolution maps of acoustic properties at 250 MHz of unstained fixed murine
      retinal layers.
AB  - Ex vivo assessment of microscale tissue biomechanical properties of the mammalian
      retina could offer insights into diseases such as keratoconus, and macular
      degeneration. A 250-MHz scanning acoustic microscope (7-MUm resolution) has been
      constructed to derive two-dimensional quantitative maps of attenuation (alpha),
      speed of sound (c), acoustic impedance (Z), bulk modulus (B), and mass density (
      rho). The two-dimensional maps were compared to coregistered hematoxylin-and
      eosin stained sections. This study is the first to quantitatively assess  alpha,
      c, Z, B, and rho of individual retinal layers of mammalian animals at high
      ultrasound frequencies. Significant differences in these parameters between the
      layers were demonstrated. 

PMID- 25994738
TI  - Prevalence and predictors of recent skin examination in a population-based twin
      cohort.
AB  - BACKGROUND: The incidence of melanoma is increasing worldwide. Guidelines for
      clinical skin exam for improving early diagnosis of melanoma remain inconsistent,
      and current data on factors associated with regular skin screening on a
      population basis are limited. METHODS: We used self-reported data from 50,044
      members of the California Twin Program, a population-based cohort of twins born
      in California between 1908 and 1982, to identify prevalence and determinants of
      recent clinical screening for skin cancer. RESULTS: Prevalence of skin
      examination was higher than national estimates, with 32% of respondents of all
      ages reporting ever having skin examination. Sociodemographic and constitutional
      risk factors including white race, educational attainment, marital status, and
      number of large moles were strongly associated with recent screening, as were
      individual and family history of skin cancer. Lower socioeconomic status,
      racial/ethnic minority status, and paradoxically, frequent UV-related risk
      behaviors in adulthood were associated with a lower likelihood of recent
      screening. CONCLUSIONS: As the evidence concerning the efficacy of skin
      examination continues to evolve, attention should be paid to motivators and
      barriers of screening, particularly in high-risk subgroups where lack of
      screening may contribute to disparate rates of thicker melanomas and lower
      survival. IMPACT: Our results demonstrate the need for prevention strategies
      targeted to specific at-risk groups to increase earlier detection leading to
      improved outcomes.

PMID- 25994739
TI  - PIK3CA Somatic Mutation Status in Relation to Patient and Tumor Factors in
      Racial/Ethnic Minorities with Colorectal Cancer.
AB  - BACKGROUND: Approximately 10% to 20% of colorectal cancers exhibit somatic
      mutations in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene
      (PIK3CA). We evaluated the relationship of PIK3CA mutation status in colorectal
      cancer with race/ethnicity, colorectal cancer survival, and other patient and
      tumor factors. METHODS: This study comprised 377 racial/ethnic minorities with
      incident invasive colorectal cancer, enrolled in the Colon Cancer Family Registry
      via population-based cancer registries. Tumor specimens were tested for PIK3CA
      mutations in exon 9 and 20 hotspots, BRAF p.V600E mutations, and DNA mismatch
      repair (MMR). In logistic regression models, we evaluated the association between
      PIK3CA mutation status and race/ethnicity, overall, and by mutation site. Using
      Cox regression, we evaluated the association between PIK3CA mutation status and
      survival after colorectal cancer diagnosis. RESULTS: PIK3CA mutations were
      detected in 42 cases (11%), with a similar prevalence across racial/ethnic
      groups. Individuals with PIK3CA-mutated colorectal cancer were significantly more
      likely than those with PIK3CA-wildtype disease to have proximal colon cancer, MMR
      deficient tumors, and a germline MMR mutation (P <= 0.01). There was no evidence
      for an association between PIK3CA and overall survival (HR, 0.77; 95% confidence
      interval, 0.43-1.39). CONCLUSIONS: The prevalence of PIK3CA mutation status in
      colorectal cancer does not differ according to race/ethnicity, but may vary
      according to other relevant clinicopathologic and etiologic factors, including
      germline MMR mutation status, tumor MMR status, and tumor site. IMPACT: These
      findings underscore the importance of PIK3CA mutation status in colorectal cancer
      epidemiology and provide evidence that the prevalence of such mutations is
      similar across several racial/ethnic groups.

PMID- 25994741
TI  - Perturbative optical parametric amplification in the extreme ultraviolet.
AB  - The response of a medium illuminated with a light field can be expanded in many
      orders in perturbative non-linear optics. Here we use two multiple-cycle high
      intensity laser pulses at 800 and 1,400 nm to generate extreme ultraviolet
      radiation where the multi-photon processes can be treated as the driving force of
      a perturbative optical parametric amplification. When a very high-intensity pulse
      (>7.10(14) W cm(-2)) at 800 nm is applied in addition to a high-intensity pulse
      at 1,400 nm, we are able to enhance the flux of the coherent extreme ultraviolet
      radiation in the photon energy range around 80 eV by more than an order of
      magnitude compared with the generation with a single-wavelength pulse. This opens
      the way to extend the powerful techniques of perturbative non-linear optics to
      the case of a high-intensity-driving field in multiple-photon processes. 

PMID- 25994743
TI  - Look beyond what seems obvious: thrombus burden after aspiration thrombectomy.

PMID- 25994740
TI  - Plasma C-reactive protein and risk of breast cancer in two prospective studies
      and a meta-analysis.
AB  - BACKGROUND: C-reactive protein (CRP) has been evaluated as a risk factor for
      breast cancer in epidemiologic studies. However, results from prospective studies
      are inconsistent. METHODS: We evaluated the association using prediagnostic blood
      samples in a case-control study nested within the Nurses' Health Study (NHS) and
      the full cohort of the Women's Health Study (WHS). A total of 943 cases in the
      NHS and 1,919 cases in the WHS contributed to the analysis. Conditional logistic
      regression and Cox proportional hazards model were used in the NHS and WHS,
      respectively. We pooled our results with prior prospective studies using random
      effect meta-analysis. RESULTS: In the NHS, higher CRP levels were associated with
      a suggestively increased risk of breast cancer [quintile 5 vs. 1: relative risk
      (RR), 1.27; 95% confidence interval (CI), 0.93-1.73; Ptrend = 0.02]; results did
      not vary significantly by tumor invasiveness or hormone receptor status. However,
      no association was observed in the WHS for overall risk (quintile 5 vs. 1: RR,
      0.89; 95% CI, 0.76-1.06; Ptrend = 0.38) or by tumor invasiveness or hormone
      receptor status. The meta-analysis (including 5,371 cases from 11 studies) showed
      a modestly increased risk among women in the highest versus lowest categories of
      CRP (RR, 1.26; 95% CI, 1.07-1.49). CONCLUSIONS: Existing data from prospective
      studies suggest that CRP, a nonspecific marker of inflammation, is modestly
      positively associated with breast cancer risk. IMPACT: Our findings provide
      support to the concept that inflammation can influence breast cancer development.

PMID- 25994742
TI  - Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary
      intervention-alone in ST-segment elevation myocardial infarction: the optical
      coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone)
      trial.
AB  - AIMS: Manual thrombectomy has been proposed as a strategy to reduce thrombus
      burden during primary percutaneous coronary intervention (PCI) in patients with
      ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of
      manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of
      the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden
      at the culprit lesion using optical coherence tomography (OCT) in patients
      treated with thrombectomy vs. PCI-alone. METHODS AND RESULTS: The TOTAL trial (N
      = 10 732) was an international, multicentre, randomized trial of thrombectomy
      (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in
      STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled
      214 patients from 13 sites in 5 countries. Optical coherence tomography was
      performed immediately after thrombectomy or PCI-alone and then repeated after
      stent deployment. Thrombus quantification was performed by an independent core
      laboratory blinded to treatment assignment. The primary outcome of pre-stent
      thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22)
      in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P
      = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74
      mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus,
      post-stent atherothrombotic burden, and post-stent atherothrombotic volume were
      not different between groups. CONCLUSION: Manual thrombectomy did not reduce pre
      stent thrombus burden at the culprit lesion compared with PCI-alone. Both
      strategies were associated with low thrombus burden at the lesion site after the
      initial intervention to restore flow.

PMID- 25994745
TI  - It is BEAUTIFUL we should be concerned about, not SIGNIFY: is ivabradine less
      effective in ischaemic compared with non-ischaemic LVSD?

PMID- 25994744
TI  - Cardiovascular diseases in populations: secular trends and contemporary
      challenges-Geoffrey Rose lecture, European Society of Cardiology meeting 2014.
AB  - Geoffrey Rose pioneered the concept that, to reduce the burden of disease,
      improving the population distribution of a risk factor was preferable to
      interventions that target high-risk individuals. Reflecting on this concept
      prompted us to ask if temporal trends in the burden of cardiovascular disease
      support this hypothesis. This perspective article summarizes the Geoffrey Rose
      lecture given at the European Society of Cardiology meeting in 2014 and examines
      how cardiovascular diseases have evolved over the past three decades focusing on
      temporal trends in myocardial infarction and heart failure. 

PMID- 25994746
TI  - The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce
      atherosclerotic cardiovascular disease risk: a new paradigm supported by more
      evidence.
AB  - AIMS: The 2013 American College of Cardiology/American Heart Association
      cholesterol guideline was a major paradigm shift and heavily criticized by some
      experts. A better understanding of the methodology used to develop the guideline,
      the guideline recommendations, and the evidence supporting them addresses many of
      criticisms. METHODS AND RESULTS: An extensive body of evidence from randomized
      clinical trials supports the new risk-based approach. The emphasis is on the
      appropriate intensity of statin therapy in patients most likely to benefit. The
      National Institute for Health and Care Excellence guidelines have taken a similar
      approach. Recent studies have found the 2013 guideline outperforms earlier
      cholesterol guidelines recommending low-density lipoprotein cholesterol (LDL-C)
      treatment thresholds and targets. The 2013 cholesterol guideline better
      identifies high-risk patients with a greater burden of atherosclerosis and avoids
      treating those at lower risk with little atherosclerosis; its application would
      prevent up to 450 000 more atherosclerotic cardiovascular disease (ASCVD) events
      over 10 years. The 2013 cholesterol guideline also recommends regularly
      monitoring LDL-C levels to assess adherence to lifestyle and drug therapy, and
      adjusting treatment based on response to therapy and adverse events. Non-statins
      shown to reduce ASCVD events when added to statin therapy, and that have an
      acceptable margin of safety in randomized, controlled clinical trials, are
      preferred. Ezetimibe has now been shown to meet this standard. CONCLUSIONS: The
      concept of net benefit introduced in the 2013 ACC/AHA cholesterol guideline
      identifies patients most likely to benefit from statin therapy to reduce ASCVD
      risk. Net benefit, incorporating the absolute ASCVD risk of a patient and the
      relative reduction in ASCVD risk based on the magnitude of LDL-C reduction from
      the addition of a non-statin, can be used when considering whether to add
      ezetimibe or another LDL-C lowering drug.

PMID- 25994747
TI  - First-in-man transapical mitral valve replacement using the Direct Flow
      Medical(r) aortic valve prosthesis.

PMID- 25994748
TI  - Cardiac perforation as a rare complication of acupuncture.

PMID- 25994749
TI  - Fulminant lymphocytic myocarditis mimicking ST-elevation myocardial infarction.

PMID- 25994750
TI  - Partial atrioventricular septal defect presenting in a septuagenarian.

PMID- 25994751
TI  - Myocarditis associated with Takayasu arteritis.

PMID- 25994752
TI  - Foetal and maternal cardiac rhabdomyomas associated with tuberous sclerosis.

PMID- 25994753
TI  - Diagnostic assessment and follow-up of cardiac sarcoidosis in a patient
      presenting with ventricular tachycardia.

PMID- 25994754
TI  - Prognostic value of CHA2DS2-VASc score in patients with 'non-valvular atrial
      fibrillation' and valvular heart disease: the Loire Valley Atrial Fibrillation
      Project.
AB  - AIMS: The CHA2DS2VASc score is a clinical risk stratification tool which
      estimates the risk of stroke and thromboembolism in non-valvular atrial
      fibrillation (AF). We aimed to establish the value of this score for risk
      evaluation in patients with non-valvular AF and valvular heart disease. METHODS
      AND RESULTS: Among 8053 patients with non-valvular AF (ESC guidelines
      definition), patients were categorized into Group 1 (no valve disease, n = 6851;
      85%) and Group 2 (valve disease with neither rheumatic mitral stenosis nor valve
      prothesis, n = 1202; 15%). After follow-up of 868 +/- 1043 days, 627 stroke/
      thromboembolic (TE) events were recorded. Group 2 was significantly older, had a
      higher CHA2DS2VASc score and had a higher risk of thromboembolic events [hazard
      ratio (HR) 1.39; 95% CI 1.14-1.69, P = 0.001] compared with Group 1. Severe valve
      disease was not associated with worse prognosis for stroke/TE events. In the two
      groups, stroke/TE risk increased with a higher CHA2DS2VASc score. Factors
      independently associated with increased risk of stroke/TE events were older age
      (HR 1.25, 95% CI 1.14-1.36 per 10-year increase, P < 0.0001) and higher
      CHA2DS2VASc score (HR 1.33, 95% CI 1.23-1.45, P < 0.0001). The predictive value
      (c-statistic) of the CHA2DS2VASc score was similar in the two groups. CONCLUSION:
      In patients with non-valvular AF, left-sided valvular heart disease (excluding
      mitral stenosis and protheses) was associated with an increased risk of stroke/TE
      events. A higher CHA2DS2VASc score in these patients is likely to explain these
      results.

PMID- 25994755
TI  - Neoatherosclerosis: overview of histopathologic findings and implications for
      intravascular imaging assessment.
AB  - Despite the reduction in late thrombotic events with newer-generation drug
      eluting stents (DES), late stent failure remains a concern following stent
      placement. In-stent neoatherosclerosis has emerged as an important contributing
      factor to late vascular complications including very late stent thrombosis and
      late in-stent restenosis. Histologically, neoatherosclerosis is characterized by
      accumulation of lipid-laden foamy macrophages within the neointima with or
      without necrotic core formation and/or calcification. The development of
      neoatherosclerosis may occur in months to years following stent placement,
      whereas atherosclerosis in native coronary arteries develops over decades.
      Pathologic and clinical imaging studies have demonstrated that neoatherosclerosis
      occurs more frequently and at an earlier time point in DES when compared with
      bare metal stents, and increases with time in both types of implant. Early
      development of neoatherosclerosis has been identified not only in first
      generation DES but also in second-generation DES. The mechanisms underlying the
      rapid development of neoatherosclerosis remain unknown; however, either absence
      or abnormal endothelial functional integrity following stent implantation may
      contribute to this process. In-stent plaque rupture likely accounts for most
      thrombotic events associated with neoatherosclerosis, while it may also be a
      substrate of in-stent restenosis as thrombosis may occur either symptomatically
      or asymptomatically. Intravascular optical coherence tomography is capable of
      detecting neoatherosclerosis; however, the shortcomings of this modality must be
      recognized. Future studies should assess the impact of iterations in stent
      technology and risk factor modification on disease progression. Similarly,
      refinements in imaging techniques are also warranted that will permit more
      reliable detection of neoatherosclerosis. 

PMID- 25994756
TI  - Valvular heart disease among non-valvular atrial fibrillation: a misnomer, in
      search of a new term.

PMID- 25994757
TI  - Developing a continental atlas of the distribution and trypanosomal infection of
      tsetse flies (Glossina species).
AB  - BACKGROUND: Tsetse flies (Genus: Glossina) are the sole cyclical vectors of
      African trypanosomoses. Despite their economic and public health impacts in sub
      Saharan Africa, it has been decades since the latest distribution maps at the
      continental level were produced. The Food and Agriculture Organization of the
      United Nations is trying to address this shortcoming through the Atlas of tsetse
      and African animal trypanosomosis. METHODS: For the tsetse component of the
      Atlas, a geospatial database is being assembled which comprises information on
      the distribution and trypanosomal infection of Glossina species. Data are
      identified through a systematic literature review. Field data collected since
      January 1990 are included, with a focus on occurrence, apparent density and
      infection rates of tsetse flies. Mapping is carried out at the level of
      site/location. For tsetse distribution, the database includes such ancillary
      information items as survey period, trap type, attractant (if any), number of
      traps deployed in the site and the duration of trapping (in days). For tsetse
      infection, the sampling and diagnostic methods are also recorded. RESULTS: As a
      proof of concept, tsetse distribution data for three pilot countries (Ethiopia,
      Kenya and Uganda) were compiled from 130 peer-reviewed publications, which
      enabled tsetse occurrence to be mapped in 1266 geographic locations. Maps were
      generated for eight tsetse species (i.e. G. brevipalpis, G. longipennis, G.
      fuscipes fuscipes, G. tachinoides, G. pallidipes, G. morsitans submorsitans, G.
      austeni and G. swynnertoni). For tsetse infection rates, data were identified in
      25 papers, corresponding to 91 sites. CONCLUSIONS: A methodology was developed to
      assemble a geo-spatial database on the occurrence, apparent density and
      trypanosomal infection of Glossina species, which will enable continental maps to
      be generated. The methodology is suitable for broad brush mapping of all tsetse
      species of medical and veterinary public health importance. For a few tsetse
      species, especially those having limited economic importance and circumscribed
      geographic distribution (e.g. fusca group), recently published information is
      scanty or non-existent. Tsetse-infested countries can adopt and adapt this
      approach to compile national Atlases, which ought to draw also on the vast amount
      of unpublished information.

PMID- 25994758
TI  - [Not Available].

PMID- 25994759
TI  - Down-regulation of malic enzyme 1 and 2: Sensitizing head and neck squamous cell
      carcinoma cells to therapy-induced senescence.
AB  - BACKGROUND: The purpose of this study was to present the results of our
      investigation of malic enzyme (ME) expression and the induction of senescence in
      head and neck squamous cell carcinoma (HNSCC). METHODS: P53, ME1, ME2, and
      aspects of cellular metabolism, such as reactive oxygen species (ROS) were
      investigated in HNSCC cell lines. RESULTS: Both metformin and ionizing radiation
      inhibited the expression of ME2, but not ME1, in HNSCC. Knockdown of ME1 or ME2
      potentiated therapy-induced senescence in HNSCC cells regardless of p53 status,
      and led to increased p21 and generation of ROS. Therapy-induced senescence in ME
      depleted cells was blocked by the antioxidant N-acetyl cysteine. Finally, high
      expression of ME2 was associated with poorer overall survival (OS) in patients
      with HNSCC. CONCLUSION: Depletion of ME enhances therapy-induced senescence and
      seems driven largely by ROS. ME2 expression in HNSCC may be associated with poor
      outcome, providing a possible link between therapy-induced senescence and patient
      outcome, and indicating a potential therapeutic benefit of targeting ME2. (c)
      2015 Wiley Periodicals, Inc. Head Neck 38: E934-E940, 2016.

PMID- 25994761
TI  - Quantitative detection of DNMT3A R882H mutation in acute myeloid leukemia.
AB  - BACKGROUND: DNMT3A mutations represent one of the most frequent gene alterations
      detectable in acute myeloid leukemia (AML) with normal karyotype. Although
      various recurrent somatic mutations of DNMT3A have been described, the most
      common mutation is located at R882 in the methyltransferase domain of the gene.
      Because of their prognostic significance and high stability during disease
      evolution, DNMT3A mutations might represent highly informative biomarkers for
      prognosis and outcome of disease. METHODS: We describe an allele-specific PCR
      with a Blocking reagent for the quantitative detection of DNMT3A R882H mutation
      providing the possibility to analyze the quantitative amount of mutation during
      the course of disease. Next, we analyzed 62 follow-up samples from 6 AML patients
      after therapy and allogeneic stem cell transplantation (alloSCT). RESULTS: We
      developed an ASB-PCR assay for quantitative analysis of R882H DNMT3A mutation.
      After optimization of blocker concentration, a R882H-positive plasmid was
      constructed to enhance the accuracy of the sensitivity of quantitative detection.
      The assay displayed a high efficiency and sensitivity up to 10(-3). The
      reproducibility of assay analyzed using follow-up samples showed the standard
      deviation less than 3.1 %. This assay displayed a complete concordance with
      sequencing and endonuclease restriction analysis. We have found persistence of
      DNMT3A R882H mutations in complete remission (CR) after standard cytoreduction
      therapy that could be indicating presence of DNMT3A mutation in early pre
      leukemic stem cells that resist chemotherapy. The loss of correlation between
      NPM1 and DNMT3A in CR could be associated with evolution of pre-leukemic and
      leukemic clones. In patients with CR with complete donor chimerism after alloSCT,
      we have found no DNMT3A R882H. In relapsed patients, all samples showed an
      increasing of both NPM1 and DNMT3A mutated alleles. This suggests at least in
      part the presence of NPM1 and DNMT3A mutations in the same cell clone.
      CONCLUSION: We developed a rapid and reliable method for quantitative detection
      of DNMT3A R882H mutations in AML patients. Quantitative detection of DNMT3A R882H
      mutations at different time points of AML disease enables screening of follow-up
      samples. This could provide additional information about the role of DNMT3A
      mutations in development and progression of AML.

PMID- 25994763
TI  - Identification of intrinsic catalytic activity for electrochemical reduction of
      water molecules to generate hydrogen.
AB  - Insufficient hydronium ion activities at near-neutral pH and under unbuffered
      conditions induce diffusion-limited currents for hydrogen evolution, followed by
      a reaction with water molecules to generate hydrogen at elevated potentials. The
      observed constant current behaviors at near neutral pH reflect the intrinsic
      electrocatalytic reactivity of the metal electrodes for water reduction. 

PMID- 25994762
TI  - Left ventricular shape and mass impact torsional dynamics in asymptomatic
      patients with chronic aortic regurgitation and normal left ventricular ejection
      fraction.
AB  - Chronic aortic regurgitation (AR) is associated with a unique pattern of left
      ventricular (LV) volume and pressure overload, leading to LV remodelling. LV
      torsional motion, a key component of LV performance, can be altered in this
      setting. We aimed to assess the impact of LV remodelling on LV torsional dynamics
      parameters using speckle-tracking echocardiography (STE) in asymptomatic AR
      patients. We prospectively enrolled 60 patients with chronic AR and LVEF > 50%
      and 55 healthy controls. LV rotation, twisting and untwisting were assessed using
      STE. Patients with AR had higher LV diameters, volumes and mass, a more spherical
      LV shape than controls, but similar LVEF. In AR patients we found reduced peak LV
      apical rotation and decreased (2.1 +/- 0.8 vs 2.9 +/- 0.9 degrees /cm, p < 0.001)
      and delayed (time to peak LV twist: 0.94 +/- 0.12 vs 0.99 +/- 0.09, p = 0.004)
      peak LV torsion. Also, peak LV untwisting velocity was decreased (-123.5 +/- 41.5
      vs -152.3 +/- 55.0 degrees /s, p = 0.002) due to lower peak LV apical diastolic
      rotation rate. LV shape influenced LV torsional dynamics, a more spherical LV
      displaying reduced peak LV apical rotation and diastolic rotation rate and
      decreased LV twist. A more hypertrophied LV had a lower peak LV torsion, peak LV
      apical diastolic rotation rate and peak LV untwisting velocity. LV apical
      rotation and torsion are decreased and LV twist is delayed in patients with
      chronic AR and normal LVEF, detecting early subclinical LV dysfunction before
      LVEF declines. Also, LV untwisting is reduced in these patients. LV remodelling
      impairs LV torsional dynamics parameters in this setting.

PMID- 25994764
TI  - Reflex Seizures Triggered by Exposure to Characters With Numerical Value: A Case
      With Right Temporal Cortical Dysplasia.
AB  - Reflex seizures can be triggered by a variety of stimuli. We present a case with
      drug-resistant complex partial seizures originating in right temporal lobe
      triggered extensively by visual, auditory, and mental exposure to multidigit
      numbers. The patient was investigated in video-EEG monitoring unit and seizures
      were triggered by numerical stimuli. Scalp EEG findings suggested a right
      temporal focus but ictal semiological findings suspicious for an extratemporal
      area necessitated the invasive EEG study. A right anterior temporal seizure focus
      was established with invasive monitoring and cortical stimulation studies.
      Magnetic resonance imaging showed a cortical dysplasia in right anterior temporal
      lobe and ictal single-photon emission computed tomography confirmed the
      epileptogenic focus, leading to a right temporal lobectomy and
      amygdalohippocampectomy and a pathological diagnosis of focal cortical dysplasia
      type Ia. The patient is seizure-free at the end of the second postoperative year
      despite repeated exposures to numbers. To our knowledge, this is the first report
      of seizures triggered by numbers. It is also of particular importance as the
      reflex seizures are associated with a cortical lesion and it may suggest
      involvement of right anterior temporal lobe in numerical processing. 

PMID- 25994765
TI  - Clinical Outcomes of Patients Treated With Pulmonary Vasodilators Early and in
      High Dose After Left Ventricular Assist Device Implantation.
AB  - Right ventricular failure (RVF) is common after left ventricular assist device
      (LVAD) implantation and a major determinant of adverse outcomes. Optimal
      perioperative right ventricular (RV) management is not well defined. We evaluated
      the use of pulmonary vasodilator therapy during LVAD implantation. We performed a
      retrospective analysis of continuous-flow LVAD implants and pulmonary vasodilator
      use at our institution between September 2004 and June 2013. Preoperative RVF
      risk was assessed using recognized variables. Sixty-five patients (80% men, 50 +/
      14 years) were included: 52% HeartWare ventricular assist device (HVAD), 11%
      HeartMate II (HMII), 17% VentrAssist, 20% Jarvik. Predicted RVF risk was
      comparable with contemporary LVAD populations: 8% ventilated, 14% mechanical
      support, 86% inotropes, 25% BUN >39 mg/dL, 23% bilirubin >=2 mg/dL, 31% RV : LV
      (left ventricular) diameter >=0.75, 27% RA : PCWP (right atrium : pulmonary
      capillary wedge pressure) >0.63, 36% RV stroke work index <6 gm-m/m(2)/beat. The
      majority (91%) received pulmonary vasodilators early and in high dose: 72% nitric
      oxide, 77% sildenafil (max 200 +/- 79 mg/day), 66% iloprost (max 126 +/- 37
      MUg/day). Median hospital stay was 26 (21) days. No patient required RV
      mechanical support. Of six (9%) patients meeting RVF criteria based on prolonged
      need for inotropes, four were transplanted, one is alive with an LVAD at 3 years,
      and one died on day 35 of intracranial hemorrhage. Two-year survival was 77% (92%
      for HMII/HVAD): transplanted 54%, alive with LVAD 21%, recovery/explanted 2%. A
      low incidence of RVF and excellent outcomes were observed for patients treated
      early during LVAD implantation with combination, high-dose pulmonary
      vasodilators. The results warrant further investigation in a randomized
      controlled study.

PMID- 25994766
TI  - Active but inoperable thrombin is accumulated in a plasma protein layer
      surrounding Streptococcus pyogenes.
AB  - Activation of thrombin is a critical determinant in many physiological and
      pathological processes including haemostasis and inflammation. Under
      physiological conditions many of these functions are involved in wound healing or
      eradication of an invading pathogen. However, when activated systemically,
      thrombin can contribute to severe and life-threatening conditions by causing
      complications such as multiple multi-organ failure and disseminated intravascular
      coagulation. In the present study we investigated how the activity of thrombin is
      modulated when it is bound to the surface of Streptococcus pyogenes. Our data
      show that S. pyogenes bacteria become covered with a proteinaceous layer when
      incubated with human plasma, and that thrombin is a constituent of this layer.
      Though the coagulation factor is found attached to the bacteria with a functional
      active site, thrombin has lost its capacity to interact with its natural
      substrates and inhibitors. Thus, the interaction of bacteria with human plasma
      renders thrombin completely inoperable at the streptococcal surface. This could
      represent a host defense mechanism to avoid systemic activation of coagulation
      which could be otherwise induced when bacteria enter the circulation and cause
      systemic infection. 

PMID- 25994767
TI  - ETD Outperforms CID and HCD in the Analysis of the Ubiquitylated Proteome.
AB  - Comprehensive analysis of the ubiquitylome is a prerequisite to fully understand
      the regulatory role of ubiquitylation. However, the impact of key mass
      spectrometry parameters on ubiquitylome analyses has not been fully explored. In
      this study, we show that using electron transfer dissociation (ETD)
      fragmentation, either exclusively or as part of a decision tree method, leads to
      ca. 2-fold increase in ubiquitylation site identifications in K-epsilon-GG
      peptide-enriched samples over traditional collisional-induced dissociation (CID)
      or higher-energy collision dissociation (HCD) methods. Precursor ions were
      predominantly observed as 3+ charged species or higher and in a mass range 300
      1200 m/z. N-ethylmaleimide was used as an alkylating agent to reduce false
      positive identifications resulting from overalkylation with halo-acetamides.
      These results demonstrate that the application of ETD fragmentation, in addition
      to narrowing the mass range and using N-ethylmaleimide yields more high
      confidence ubiquitylation site identification than conventional CID and HCD
      analysis.

PMID- 25994768
TI  - Cutaneous siderosis secondary to intramuscular iron dextran treated with 755 nm Q
      switched alexandrite laser: A case report.
AB  - BACKGROUND: Cutaneous siderosis is accumulation of iron in the dermis and the
      subcutaneous tissue secondary to extravasation of an intramuscular or
      intravascular iron injection. It presents as varying shades of brown macules with
      no distinct contours. The hyperpigmentation is permanent without treatment.
      OBJECTIVE: Q-switched lasers have been used effectively to treat lentigines and
      tattoos however, there is little data on the treatment of cutaneous siderosis
      with lasers. Our objective was to effectively treat cutaneous siderosis with a Q
      switched alexandrite laser. RESULTS: A 50-year-old female had received nine
      injections of intramuscular iron dextran, one injection every 2 weeks alternating
      right buttock and left buttock over the course of 5 months. A couple of weeks
      after her 9th injection which was on the left, she noted brown hyperpigmentation
      in the injection area with the left worse than the right. She waited 3 months for
      the hyperpigmentation to self-resolve before presenting in our clinic. We
      utilized the Q-switched alexandrite laser to treat the patient with a test spot.
      One week later, there was nice partial clearance from the test spot so we
      commenced full treatment of the hyperpigmentation. There was significant
      improvement after the first treatment and she has been treated 4 times with
      continued improvement over the past 2 months. CONCLUSION: The Q-switched
      alexandrite laser is a useful tool in the treatment of cutaneous siderosis
      secondary to iron injection.

PMID- 25994769
TI  - Maternal uniparental isodisomy (iUPD) of chromosome 4 in a subject with mild
      intellectual disability and speech delay.

PMID- 25994778
TI  - Gastric Band Surgery Leads to Improved Insulin Secretion in Overweight People
      with Type 2 Diabetes.
AB  - BACKGROUND: We aimed to determine the effects of laparoscopic adjustable gastric
      band (LAGB) on beta-cell function in overweight people with type 2 diabetes and
      to assess the relationship between baseline beta-cell function and glycemic
      outcomes. METHODS: We studied 44 overweight but not obese people with type 2
      diabetes who participated in a randomized trial whose primary outcome was the
      rate of diabetes remission after 2 years of multidisciplinary diabetes care (MDC
      group) or multidisciplinary care combined with LAGB. Dynamic beta-cell function
      was assessed by intravenous glucose challenge, and basal beta-cell function (HOMA
      B) and insulin sensitivity (HOMA-S) were determined using the homeostatic model.
      RESULTS: Twelve LAGB participants and two MDC participants were in diabetes
      remission at 2 years. HOMA-S and the C-peptide response to intravenous glucose
      increased significantly in LAGB but not in MDC participants. The insulin response
      to glucose did not change in LAGB participants, whereas their fasting C
      peptide/insulin ratio increased. Baseline measures of beta-cell function
      correlated with diabetes remission but not with reduction in HbA1c following
      LAGB. CONCLUSIONS: In overweight people with diabetes, LAGB improves endogenous
      beta-cell function after 2 years. Baseline beta-cell function correlated with
      diabetes remission, but not with HbA1c change following LAGB.

PMID- 25994780
TI  - Preoperative Interventions for Patients Being Considered for Bariatric Surgery:
      Separating the Fact from Fiction.
AB  - Preoperative interventions aimed at patients referred for bariatric surgery
      continue to divide funders, commissioners, and practitioners alike. A number of
      preoperative interventions and variables have been used to influence patient
      selection. Many of these are believed to lead to better postoperative outcomes by
      helping target a limited resource (bariatric surgery) at those most likely to
      benefit. Inevitably, this leads to competition amongst patients and some being
      denied benefits of surgery. There is a risk that these strategies for resource
      allocation may actually deprive the most vulnerable and those most in need. This
      review examines evidence and justification behind popular preoperative
      interventions for patients being considered for bariatric surgery patients in the
      light of published English language scientific literature. 

PMID- 25994779
TI  - Influence of Roux-en-Y Gastric Bypass on the Nutritional Status of Vitamin A in
      Pregnant Women: a Comparative Study.
AB  - OBJECTIVE: The objective of the present study is to evaluate the nutritional
      status of vitamin A through biochemical and functional indicators of pregnant
      women who underwent Roux-en-Y gastric bypass (RYGB) surgery compared to pregnant
      women who did not undergo this surgery. METHODS: The present study is a cross
      sectional study of the analytical type with pregnant women paired by age and
      prepregnancy body mass index (BMI). Group 1 (G1) comprised 80 pregnant women
      without previous submission to RYGB and group 2 (G2) by 40 pregnant women who
      previously underwent this surgery. We used high-performance liquid chromatography
      with UV detector for quantification of retinol and beta-carotene, and the
      functional evaluation of vitamin A deficiency (VAD) was performed through
      standardized interview validated for pregnant women. RESULTS: G1 mean age was
      29.3 +/- 5.3 and 30.8 +/- 4.4 in G2. BMI mean prepregnancy found in G1 was 25.7
      +/- 3.2 and 26.8 +/- 3.1 in G2, featuring overweight. Serum retinol and beta
      carotene means were significantly higher in G1 (1.8 +/- 0.9; 87.4 +/- 62.2)
      compared to G2 (0.99 +/- 0.39; 22.7 +/- 18.0), respectively (p < 0.001).
      Regarding the functional indicator for evaluation of VAD, approximately 75.0 % of
      pregnant women in G2 showed night blindness and 20.0 % in G1, and the percentage
      of pregnant women with this functional impairment was significantly higher in G2
      compared to G1 with p < 0.001. CONCLUSION: Results show that pregnancy after RYGB
      can represent a high-risk situation for VAD. We recommend interdisciplinary
      monitoring added to the prenatal routine consultations and the conduction of
      studies addressed to the investigation of a safe and effective dose of oral
      supplementation of vitamin A to pregnant women undergoing RYGB.

PMID- 25994781
TI  - Letter to the editor: a case of an extraadrenal paraganglioma in the sigma in a
      patient with recurrent sigmadiverticulitis.

PMID- 25994783
TI  - Twin sisters with perforated sigmoid diverticulitis support heredity in the
      pathogenesis of diverticular disease.

PMID- 25994782
TI  - The impact of perianal disease in young patients with inflammatory bowel disease.
AB  - BACKGROUND: Perianal disease is a potentially significant source of morbidity for
      patients with inflammatory bowel disease (IBD). We sought to identify the impact
      of perianal disease on IBD outcomes in children, adolescents, and young adults.
      METHODS: We studied 12,465 inpatient admissions for patients <=20 years old with
      IBD in 2009 using the Kids' Inpatient Database (KID). Patients were stratified by
      their principal diagnosis of ulcerative colitis (UC) or Crohn's disease (CD).
      Perianal disease (perianal abscess, anal fissure, or anal fistula), complex
      fistulas (rectourethral, rectovaginal, or enterovesical), and growth failure were
      defined by ICD-9 codes. Logistic regression was performed adjusting for CD or UC,
      gender, age, need for surgical intervention, fistulas, or growth failure.
      RESULTS: Of the 511 (4.1%) patients with perianal disease, 480 had CD (94%, p <
      0.001). Girls were less likely to suffer perianal disease (OR = 0.63, CI 0.52
      0.76, p < 0.001). Those with perianal disease were more likely to suffer complex
      fistulas (OR = 3.5, CI 1.98-6.20, p < 0.001) but less likely to suffer
      enteroenteral fistulas (OR = 0.30, CI 0.15-0.63, p = 0.001) than those without
      perianal disease. Perianal disease did not increase the incidence of growth
      failure (p = 0.997) but doubled the likelihood of an operation of any type during
      admission (p < 0.001). Additionally, patients with perianal disease spent on
      average 1.29 more days in the hospital (7.45 vs. 6.16 days, p < 0.001) and
      accrued $5838 extra in hospital charges (p = 0.005). CONCLUSIONS: Perianal
      disease in younger patients is associated with a longer length of stay, higher
      hospital charges, and increased rates of both perineal and abdominal operative
      procedures. These data support the notion that, similar to adults, the presence
      of perianal disease in pediatric Crohn's patients is associated with a more
      severe course.

PMID- 25994784
TI  - First description of the association of two rare diseases with familial
      adenomatous polyposis (FAP).

PMID- 25994785
TI  - Tropical herbivores provide resilience to a climate-mediated phase shift on
      temperate reefs.
AB  - Climate-mediated changes to biotic interactions have the potential to
      fundamentally alter global ecosystems. However, the capacity for novel
      interactions to drive or maintain transitions in ecosystem states remains
      unresolved. We examined temperate reefs that recently underwent complete seaweed
      canopy loss and tested whether a concurrent increase in tropical herbivores could
      be maintaining the current canopy-free state. Turf-grazing herbivorous fishes
      increased in biomass and diversity, and displayed feeding rates comparable to
      global coral reefs. Canopy-browsing herbivores displayed high (~ 10,000 g 100 m(
      2) ) and stable biomass between 2006 and 2013. Tropical browsers had the highest
      abundance in 2013 and displayed feeding rates approximately three times higher
      than previously observed on coral reefs. These observations suggest that tropical
      herbivores are maintaining previously kelp-dominated temperate reefs in an
      alternate canopy-free state by grazing turfs and preventing kelp reestablishment.
      This remarkable ecosystem highlights the sensitivity of biotic interactions and
      ecosystem stability to warming and extreme disturbance events.

PMID- 25994786
TI  - Molecular communication: crosstalk between the Snf1 and other signaling pathways.
AB  - The yeast Saccharomyces cerevisiae employs different conserved signaling pathways
      to adapt to altered availability of nutrient and energy sources. Crosstalk
      between the pathways occurs to integrate different internal and external stimuli
      and adjust cellular metabolism, growth and proliferation to altered environmental
      conditions. The main glucose repression pathway, Snf1/Mig1, plays an essential
      role in adaptation to glucose limitation. However, the Snf1 protein kinase is
      also involved in regulation of many other cellular processes. We summarize
      evidence that Snf1 is part of a network of communicating pathways, and we suggest
      research directions that may help elucidating signal flow within this network. 

PMID- 25994787
TI  - Flow cytometric maturity score as a novel prognostic parameter in patients with
      acute myeloid leukemia.
AB  - The European LeukemiaNet (ELN) classification is widely accepted for risk
      stratification of patients with acute myeloid leukemia (AML). In order to
      establish immunophenotypic features that predict prognosis, the expression of
      single AML blast cell antigens has been evaluated with partly conflicting
      results; however, the influence of immunophenotypic blast maturity is largely
      unknown. In our study, 300 AML patients diagnosed at our institution between
      January 2003 and April 2012 were analyzed. A flow cytometric maturity score was
      developed in order to distinguish "mature" AML (AML-ma) from "immature" AML (AML
      im) by quantitative expression levels of early progenitor cell antigens (CD34,
      CD117, and TdT). AML-ma showed significantly longer relapse-free survival (RFS)
      and overall survival (OS) than AML-im (p < 0.001). Interestingly, statistically
      significant differences in RFS and OS were maintained within the "intermediate
      risk" group according to ELN (RFS, 7.0 years (AML-ma) vs. 3.3 years (AML-im); p =
      0.002; OS, 5.1 years (AML-ma) vs. 3.0 years (AML-im); p = 0.022). Our novel flow
      cytometric score easily determines AML blast maturity and can predict clinical
      outcome. It remains to be clarified whether these results simply reflect an
      accumulation of favorable molecular phenotypes in the AML-ma subgroup or whether
      they rely on biological differences such as a higher proportion of leukemia stem
      cells and/or a higher degree of genetic instability within the AML-im subgroup.

PMID- 25994788
TI  - Thiol-based antioxidants elicit mitochondrial oxidation via respiratory complex
      III.
AB  - Excessive oxidation is widely accepted as a precursor to deleterious cellular
      function. On the other hand, an awareness of the role of reductive stress as a
      similar pathological insult is emerging. Here we report early dynamic changes in
      compartmentalized glutathione (GSH) redox potentials in living cells in response
      to exogenously supplied thiol-based antioxidants. Noninvasive monitoring of
      intracellular thiol-disulfide exchange via a genetically encoded biosensor
      targeted to cytosol and mitochondria revealed unexpectedly rapid oxidation of the
      mitochondrial matrix in response to GSH ethyl ester or N-acetyl-l-cysteine.
      Oxidation of the probe occurred within seconds in a concentration-dependent
      manner and was attenuated with the membrane-permeable ROS scavenger tiron. In
      contrast, the cytosolic sensor did not respond to similar treatments.
      Surprisingly, the immediate mitochondrial oxidation was not abrogated by
      depolarization of mitochondrial membrane potential or inhibition of mitochondrial
      GSH uptake. After detection of elevated levels of mitochondrial ROS, we
      systematically inhibited multisubunit protein complexes of the mitochondrial
      respiratory chain and determined that respiratory complex III is a downstream
      target of thiol-based compounds. Disabling complex III with myxothiazol
      completely blocked matrix oxidation induced with GSH ethyl ester or N-acetyl-l
      cysteine. Our findings provide new evidence of a functional link between
      exogenous thiol-containing antioxidants and mitochondrial respiration.

PMID- 25994789
TI  - tert-Butylhydroquinone mobilizes intracellular-bound zinc to stabilize Nrf2
      through inhibiting phosphatase activity.
AB  - The nuclear factor erythroid 2-related factor 2 (Nrf2) is required to combat
      increases in oxidative stress. The chemical compound tert-butylhydroquinone
      (tBHQ) can downregulate Kelch-like ECH-associated protein 1 (Keap1), a repressor
      of Nrf2, thus maintaining the stability of Nrf2. tBHQ can also increase
      intracellular "free" zinc in human bronchial epithelial (16HBE) cells. We aim to
      investigate whether the intracellular free zinc change plays a role in Nrf2
      activation. tBHQ exposure dose-dependently increases intracellular free zinc
      concentrations within 30 min in 16HBE cells by mobilizing intracellular zinc
      pools. Active Nrf2 and the antioxidant enzyme heme oxygenase-1 (HO-1) increase at
      3 h after tBHQ treatment. Chelating intracellular free zinc with tetrakis-(2
      pyridylmethyl)ethylenediamine (TPEN) during tBHQ exposure partially abrogates the
      tBHQ-induced activation of Nrf2 and HO-1 expression, while Keap1 is further
      decreased. These results indicate that tBHQ-induced stability of Nrf2 is
      associated with the intracellular free zinc level. Because the activated Nrf2 is
      phosphorylated, the serine/threonine protein phosphatase activity, which is known
      to be inhibited by zinc, is assayed. The results showed that tBHQ treatment can
      suppress cellular protein phosphatase-2A (PP2A) and protein phosphatase-2C (PP2C)
      activity, which can be abrogated by adding TPEN. This finding is verified in a
      cell-free protein extract experiment by supplying zinc or by chelating zinc with
      TPEN. These results provide a novel mechanistic insight into Nrf2 activation in
      antioxidant enzyme induction involving zinc signaling. The increase of
      intracellular free zinc may be one mechanism for Nrf2 activation. The inhibition
      of PP2A and PP2C activity may be involved in Nrf2 phosphorylation modulation.

PMID- 25994790
TI  - Cardiac glycosides induced toxicity in human cells expressing alpha1-, alpha2-,
      or alpha3-isoforms of Na-K-ATPase.
AB  - The Na+-K+-ATPase is specifically inhibited by cardiac glycosides, some of which
      may also function as endogenous mammalian hormones. Previous studies using
      Xenopus oocytes, yeast cells, or purified isoforms demonstrated that affinities
      of various cardiac glycosides for three isoforms of the Na+-K+-ATPase (alpha1
      alpha3beta1) may differ, a finding with potential clinical implication. The
      present study investigates isoform selectivity and effects of cardiac glycosides
      on cultured mammalian cells under more physiological conditions. H1299 cells (non
      small cell lung carcinoma) were engineered to express only one alpha-isoform
      (alpha1, alpha2, or alpha3) by combining stable transfection of isoforms and
      silencing endogenous alpha1. Cardiac glycoside binding was measured by
      displacement of bound 3H-ouabain. The experiments confirm moderate
      alpha1/alpha3:alpha2 selectivity of ouabain, moderate alpha2:alpha1 selectivity
      of digoxin, and enhanced alpha2:alpha1 selectivity of synthetic derivatives (Katz
      A, Tal DM, Heller D, Haviv H, Rabah B, Barkana Y, Marcovich AL, Karlish SJD. J
      Biol Chem 289: 21153-21162, 2014). Relative alpha2:alpha1 selectivity of digoxin
      vs. ouabain was also manifested by enhanced internalization of alpha2 in response
      to digoxin. Cellular proliferation assays of H1299 cells confirmed the patterns
      of alpha2:alpha1 selectivity for ouabain, digoxin, and a synthetic derivative and
      reveal a crucial role of surface pump density on sensitivity to cardiac
      glycosides. Because cardiac glycosides are being considered as drugs for
      treatment of cancer, effects of ouabain on proliferation of 12 cancer and
      noncancer cell lines, with variable plasma membrane expression of alpha1, have
      been tested. These demonstrated that sensitivity to ouabain indeed depends
      linearly on the plasma membrane surface density of Na+-K+-ATPase irrespective of
      status, malignant or nonmalignant.

PMID- 25994791
TI  - The dichotomous view on IFG lesion and non-fluent aphasia.
AB  - A lesion in inferior frontal gyrus (IFG) is traditionally considered to be
      crucial for the occurrence of non-fluent aphasia. However, recent studies
      question the axiomatic causality between a lesion in this area and the expected
      non-fluent aphasic syndrome. The aim of the present study is to investigate the
      relationship between IFG lesions and non-fluent aphasia. To address this
      question, we present radiological and neuropsychological data of 49 chronic
      aphasic patients. Lesions were identified based on CT and/or MRI scans. Aphasia
      was assessed using the Boston Diagnostic Aphasia Examination-short form. Analysis
      indicated a statistically significant association between IFG lesion and non
      fluent aphasic disturbances. Nevertheless, a large proportion of our patients did
      not confirm the traditional prediction, namely that non-fluent patients' lesions
      would include the inferior frontal gyrus and the opposite would be true for
      fluent patients. Our results stress the importance of taking into account the
      size of particular estimates when conducting group analyses. We also argue in
      favor of examining individual data in clinical practice, and further suggest that
      the traditional lesion to syndrome correspondence seems to be oversimplified and
      should be thoroughly revisited.

PMID- 25994792
TI  - Dutch government in court for violating international tobacco treaty.

PMID- 25994793
TI  - The use of Bruton's tyrosine kinase inhibition as a bridging strategy to
      successful allogeneic stem cell transplant in relapsed mantle cell lymphoma.

PMID- 25994794
TI  - A flexible polymer confined inside a cone-shaped nano-channel.
AB  - The nano-scale confinement of polymers in cone-shaped geometries occurs in many
      experimental situations. A flexible polymer confined in a cone-shaped nano
      channel is studied theoretically and by using molecular dynamics simulations.
      Distribution of the monomers inside the channel, configuration of the confined
      polymer, the entropic force acting on the polymer, and their dependence on the
      channel and the polymer parameters are investigated. The theory and the
      simulation results are in very good agreement. The entropic force on the polymer
      that results from the asymmetric shape of the channel is measured in the
      simulations and its magnitude is found to be significant relative to thermal
      energy. The obtained dependence of the force on the channel parameters may be
      useful in the design of cone-shaped nano-channels. 

PMID- 25994795
TI  - The Importance of Quasi-4D Path-Integrated Dose Accumulation for More Accurate
      Risk Estimation in Stereotactic Liver Radiotherapy.
AB  - Intrafraction organ deformation may be accounted for by inclusion of temporal
      information in dose calculation models. In this article, we demonstrate a quasi-4
      dimensional method for improved risk estimation. Conventional 3-dimensional and
      quasi-4-dimensional calculations employing dose warping for dose accumulation
      were undertaken for patients with liver metastases planned for 42 Gy in 6
      fractions of stereotactic body radiotherapy. Normal tissue complication
      probabilities and stochastic risks for radiation-induced carcinogenesis and
      cardiac complications were evaluated for healthy peripheral structures.
      Hypothetical assessments of other commonly employed dose/fractionation schedules
      on normal tissue complication probability estimates were explored. Conventional 3
      dimensional dose computation may result in significant under- or overestimation
      of doses to organ at risk. For instance, doses differ (on average) by 17% (sigma
      = 14%) for the left kidney, by 14% (sigma = 7%) for the right kidney, by 7%
      (sigma = 9%) for the large bowel, and by 10% (sigma = 14%) for the duodenum.
      Discrepancies in the excess relative risk range up to about 30%. The 3
      dimensional approach was shown to result in cardiac complication risks
      underestimated by >20%. For liver stereotactic body radiotherapy, we have shown
      that conventional 3-dimensional dose calculation may significantly over
      /underestimate dose to organ at risk (90%-120% of the 4-dimensional estimate for
      the mean dose and 20%-150% for D2%). Providing dose estimates that most closely
      represent the actual dose delivered will provide valuable information to improve
      our understanding of the dose response for partial volume irradiation using
      hypofractionated schedules. Excess relative risks of radiocarcinogenesis were
      shown to range up to approximately excess relative risk = 4 and the prediction
      thereof depends greatly on the use of either 3-dimensional or 4-dimensional
      methods (with corresponding results differing by tens of percent).

PMID- 25994796
TI  - Human chorionic gonadotropin is expressed virtually in all intracranial germ cell
      tumors.
AB  - Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic
      marker for germinoma with syncytiotrophoblastic giant cells (STGC) and
      choriocarcinoma. Elevated hCG in germinoma is considered to predict less
      favorable prognosis, and an intensive treatment strategy may accordingly be
      applied. However, there is some evidence that any germinoma may produce hCG to
      varying extent. We investigated mRNA expression of the hCG beta subunit (hCGbeta)
      using real time quantitative polymerase chain reaction in 94 germ cell tumors
      (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of
      normal brain tissue (1.09 * 10(0)-1.40 * 10(5) fold). The expression was the
      highest in GCTs which harbor choriocarcinoma or STGC components. The expression
      level of hCGbeta in germinoma was highly variable (1.09 * 10(0)-5.88 * 10(4)
      fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF
      correlated with gene expression, especially when GCTs with single histological
      component were analyzed separately. The expression was not significantly
      associated with recurrence in pure germinoma. These results suggest that the
      serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear
      to have the capacity of producing hCG irrespective of their histology. The
      clinical significance of ubiquitous hCG expression in GCTs needs further
      investigation. 

PMID- 25994797
TI  - A generalized slab-wise framework for parallel transmit multiband RF pulse
      design.
AB  - PURPOSE: We propose a new slab-wise framework to design parallel transmit
      multiband pulses for volumetric simultaneous multislice imaging with a large
      field of view along the slice direction (FOVs). THEORY AND METHODS: The slab-wise
      framework divides FOVs into a few contiguous slabs and optimizes pulses for each
      slab. Effects of relevant design parameters including slab number and transmit B1
      (B1+) mapping slice placement were investigated for human brain imaging by
      designing pulses with global or local SAR control based on electromagnetic
      simulations of a 7T head RF array. Pulse design using in vivo B1+ maps was
      demonstrated and evaluated with Bloch simulations. RESULTS: RF performance with
      respect to SAR reduction or B1+ homogenization across the entire human brain
      improved with increasing slabs; however, this improvement was nonlinear and
      leveled off at ~12 slabs when the slab thickness reduced to ~12 mm. The impact of
      using different slice placements for B1+ mapping was small. CONCLUSION: Compared
      with slice-wise approaches where each of the many imaging slices requires both
      B1+ mapping and pulse optimization, the proposed slab-wise design framework
      attained comparable RF performance while drastically reducing the number of
      required pulses; therefore, it can be used to increase time efficiency for B1+
      mapping, pulse calculation, and sequence preparation.

PMID- 25994798
TI  - The angular distributions of ultraviolet spectral irradiance at different solar
      elevation angles under clear sky conditions.
AB  - To investigate the angular distributions of UVA, UVB, and effective UV for
      erythema and vitamin D (vitD) synthesis, the UV spectral irradiances were
      measured at ten inclined angles (from 0 degrees  to 90 degrees ) and seven
      azimuths (from 0 degrees  to 180 degrees ) at solar elevation angle (SEA) that
      ranged from 18.8 degrees  to 80 degrees  in Shanghai (31.22 degrees  N, 121.55
      degrees  E) under clear sky and the albedo of ground was 0.1. The results
      demonstrated that in the mean azimuths and with the back to the sun, the UVA,
      UVB, and erythemally and vitD-weighted irradiances increased with the inclined
      angles and an increase in SEA. When facing toward the sun at 0 degrees -60
      degrees  inclined angles, the UVA first increased and then decreased with an
      increase in SEA; at other inclined angles, the UVA increased with SEA. At 0
      degrees -40 degrees  inclined angles, the UVB and erythemally and vitD-weighted
      irradiances first increased and then decreased with an increase in SEA, and their
      maximums were achieved at SEA 68.7 degrees ; at other inclined angles, the above
      three irradiances increased with an increase in SEA. The maximum UVA, UVB, and
      erythemally and vitD-weighted irradiances were achieved at an 80 degrees 
      inclined angle at SEA 80 degrees  (the highest in our measurements); the
      cumulative exposure of the half day achieved the maximum at a 60 degrees 
      inclined angle, but not on the horizontal. This study provides support for the
      assessment of human skin sun exposure. 

PMID- 25994799
TI  - Advanced modelling of the transport phenomena across horizontal clothing
      microclimates with natural convection.
AB  - The ability of clothing to provide protection against external environments is
      critical for wearer's safety and thermal comfort. It is a function of several
      factors, such as external environmental conditions, clothing properties and
      activity level. These factors determine the characteristics of the different
      microclimates existing inside the clothing which, ultimately, have a key role in
      the transport processes occurring across clothing. As an effort to understand the
      effect of transport phenomena in clothing microclimates on the overall heat
      transport across clothing structures, a numerical approach was used to study the
      buoyancy-driven heat transfer across horizontal air layers trapped inside air
      impermeable clothing. The study included both the internal flow occurring inside
      the microclimate and the external flow occurring outside the clothing layer, in
      order to analyze the interdependency of these flows in the way heat is
      transported to/from the body. Two-dimensional simulations were conducted
      considering different values of microclimate thickness (8, 25 and 52 mm),
      external air temperature (10, 20 and 30  degrees C), external air velocity (0.5,
      1 and 3 m s(-1)) and emissivity of the clothing inner surface (0.05 and 0.95),
      which implied Rayleigh numbers in the microclimate spanning 4 orders of magnitude
      (9 * 10(2)-3 * 10(5)). The convective heat transfer coefficients obtained along
      the clothing were found to strongly depend on the transport phenomena in the
      microclimate, in particular when natural convection is the most important
      transport mechanism. In such scenario, convective coefficients were found to vary
      in wavy-like manner, depending on the position of the flow vortices in the
      microclimate. These observations clearly differ from data in the literature for
      the case of air flow over flat-heated surfaces with constant temperature (which
      shows monotonic variations of the convective heat transfer coefficients, along
      the length of the surface). The flow patterns and temperature fields in the
      microclimates were found to strongly depend on the characteristics of the
      external boundary layer forming along the clothing and on the distribution of
      temperature in the clothing. The local heat transfer rates obtained in the
      microclimate are in marked contrast with those found in the literature for
      enclosures with constant-temperature active walls. These results stress the
      importance of coupling the calculation of the internal and the external flows and
      of the heat transfer convective and radiative components, when analyzing the way
      heat is transported to/from the body.

PMID- 25994800
TI  - Cationic PTD/CPP-mediated macromolecular delivery: charging into the cell.
AB  - INTRODUCTION: Macromolecular therapeutics, including enzymes, transcription
      factors, siRNAs, peptides and large synthetic molecules, can potentially be used
      to treat human diseases by targeting intracellular molecular pathways and
      modulating biological responses. However, large macromolecules have no ability to
      enter cells and require delivery vehicles. Protein transduction domains (PTDs),
      also known as cell-penetrating peptides (CPPs), are a diverse class of peptides
      that can deliver macromolecules into cells. AREAS COVERED: In this review, we
      cover the uptake and usage of arginine-rich PTDs/CPPs (TAT-PTD, Penetratin/Antp
      and 8R). We review the endocytosis-mediated uptake of these peptides and
      highlight three important steps: i) cell association; ii) internalization and
      iii) endosomal escape. We also discuss the array of different cargos that have
      been delivered by cationic PTDs/CPPs as well as cellular processes and biological
      responses that have been modulated. EXPERT OPINION: PTDs/CPPs have shown great
      potential to deliver otherwise undeliverable macromolecular therapeutics into
      cells for experimentation in cell culture and in animal disease models in vivo.
      Moreover, over 25 clinical trials have been performed predominantly using the TAT
      PTD. However, more work is still needed. Endosomal escape and target-cell
      specificity remain two of the major future challenges.

PMID- 25994801
TI  - Reactively sputtered nickel nitride as electrocatalytic counter electrode for dye
      and quantum dot-sensitized solar cells.
AB  - Nickel nitride electrodes were prepared by reactive sputtering of nickel under a
      N2 atmosphere at room temperature for application in mesoscopic dye- or quantum
      dot- sensitized solar cells. This facile and reliable method led to the formation
      of a Ni2N film with a cauliflower-like nanostructure and tetrahedral crystal
      lattice. The prepared nickel nitride electrodes exhibited an excellent chemical
      stability toward both iodide and polysulfide redox electrolytes. Compared to
      conventional Pt electrodes, the nickel nitride electrodes showed an inferior
      electrocatalytic activity for the iodide redox electrolyte; however, it displayed
      a considerably superior electrocatalytic activity for the polysulfide redox
      electrolyte. As a result, compared to dye-sensitized solar cells (DSCs), with a
      conversion efficiency (eta) = 7.62%, and CdSe-based quantum dot-sensitized solar
      cells (QDSCs, eta = 2.01%) employing Pt counter electrodes (CEs), the nickel
      nitride CEs exhibited a lower conversion efficiency (eta = 3.75%) when applied to
      DSCs, but an enhanced conversion efficiency (eta = 2.80%) when applied to CdSe
      based QDSCs.

PMID- 25994802
TI  - Evaluating the impact of hippocampal sparing during whole brain radiotherapy on
      neurocognitive functions: A preliminary report of a prospective phase II study.
AB  - BACKGROUND: Whole brain radiotherapy (WBRT) is the treatment of choice for
      patients with brain metastases. However, neurocognitive functions (NCFs) decline
      due to impaired hippocampal neurogenesis might occur thereafter. It is
      hypothesized that conformal hippocampal avoidance during the course of WBRT (HA
      WBRT) might provide meaningful NCF preservation. Our study aims to demonstrate
      the impact of delivering HA-WBRT on NCF changes in patients receiving WBRT.
      METHODS: Twenty-five patients who were referred for prophylactic cranial
      irradiation (PCI) or treating oligometastatic brain disease were enrolled in the
      study. Before the HA-WBRT course, all participants should receive baseline
      neurocognitive assessment, including memory, executive functions, and psychomotor
      speed. The primary endpoint was delayed recall, as determined by the
      change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III)-
      Word List score] from the baseline assessment to 4 months after the start of HA
      WBRT. RESULTS: Only three patients belonged to the clinical setting of PCI; the
      remaining 22 patients had oligometastatic brain disease. Regarding neurocognitive
      outcomes, no statistically significant differences were found between various NCF
      scores obtained at baseline and at post-radiotherapy intervals, in immediate
      verbal memory and non-verbal memory, except for delayed recall memory on Word
      List (F = 5.727, p = 0.048). CONCLUSIONS: Functional preservation by hippocampal
      sparing during WBRT could largely be achieved in this study, which also suggests
      that HA-WBRT should be a feasible technique preserving neurocognitive functions
      while maintaining intracranial control.

PMID- 25994803
TI  - Preschool Wheeze is Not Asthma: A Clinical Dilemma - Authors' Reply.

PMID- 25994804
TI  - Influence of Backbone Fluorination in Regioregular Poly(3-alkyl-4
      fluoro)thiophenes.
AB  - We report two strategies toward the synthesis of 3-alkyl-4-fluorothiophenes
      containing straight (hexyl and octyl) and branched (2-ethylhexyl) alkyl groups.
      We demonstrate that treatment of the dibrominated monomer with 1 equiv of alkyl
      Grignard reagent leads to the formation of a single regioisomer as a result of
      the pronounced directing effect of the fluorine group. Polymerization of the
      resulting species affords highly regioregular poly(3-alkyl-4-fluoro)thiophenes.
      Comparison of their properties to those of the analogous non-fluorinated polymers
      shows that backbone fluorination leads to an increase in the polymer ionization
      potential without a significant change in optical band gap. Fluorination also
      results in an enhanced tendency to aggregate in solution, which is ascribed to a
      more co-planar backbone on the basis of Raman and DFT calculations. Average
      charge carrier mobilities in field-effect transistors are found to increase by up
      to a factor of 5 for the fluorinated polymers. 

PMID- 25994805
TI  - Distinct regulation of hypothalamic and brown/beige adipose tissue activities in
      human obesity.
AB  - BACKGROUND/OBJECTIVES: The identification of brown/beige adipose tissue in adult
      humans has motivated the search for methods aimed at increasing its thermogenic
      activity as an approach to treat obesity. In rodents, the brown adipose tissue is
      under the control of sympathetic signals originating in the hypothalamus.
      However, the putative connection between the depots of brown/beige adipocytes and
      the hypothalamus in humans has never been explored. The objective of this study
      was to evaluate the response of the hypothalamus and brown/beige adipose tissue
      to cold stimulus in obese subjects undergoing body mass reduction following
      gastric bypass. SUBJECTS/METHODS: We evaluated twelve obese, non-diabetic
      subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects
      were evaluated before and approximately 8 months after gastric bypass. Lean
      subjects were evaluated only at admission. Subjects were evaluated for
      hypothalamic activity in response to cold by functional magnetic resonance,
      whereas brown/beige adipose tissue activity was evaluated using a (F 18)
      fluorodeoxyglucose positron emisson tomography/computed tomography scan and real
      time PCR measurement of signature genes. RESULTS: Body mass reduction resulted in
      a significant increase in brown/beige adipose tissue activity in response to
      cold; however, no change in cold-induced hypothalamic activity was observed after
      body mass reduction. No correlation was found between brown/beige adipose tissue
      activation and hypothalamus activity in obese subjects or in lean controls.
      CONCLUSIONS: In humans, the increase in brown/beige adipose tissue activity
      related to body mass reduction occurs independently of changes in hypothalamic
      activity as determined by functional magnetic resonance.

PMID- 25994806
TI  - Lack of mature lymphocytes results in obese but metabolically healthy mice when
      fed a high-fat diet.
AB  - BACKGROUND/OBJECTIVES: Obesity is characterized by chronic inflammation and
      immune dysregulation, as well as insulin resistance, but the link between obesity
      and adaptive immunity remains to be fully studied. METHODS: To elucidate the role
      of adaptive immunity on body composition, glucose homeostasis and inflammation,
      recombination-activating gene 1 knockout (Rag1-/-) mice, without mature T
      lymphocytes or B-lymphocytes, were maintained on a low- or high-fat diet (LFD and
      HFD, respectively) for 11 weeks. RESULTS: Rag1-/- mice fed HFD gained
      significantly more weight and had increased body fat compared with wild type.
      Downregulation of energy expenditure as well as brown fat uncoupling protein UCP
      1 and UCP-3 gene expression were noticed in HFD-fed Rag1-/- mice compared with
      LFD. HFD mice had significantly decreased energy intake compared with LFD mice,
      consistent with decreased agouti-related protein and increased pro
      opiomelanocortin gene expression levels in the hypothalamus. Moreover, compared
      with wild type, Rag1-/- mice had lower interleukin (IL)-4 levels, a cytokine
      recently found to induce browning in white adipocytes, and higher IL-12 levels in
      HFD-fed Rag1-/- mice. Despite that HFD Rag1-/- mice were more obese, they had
      similar glucose, insulin and adiponectin levels, while leptin was marginally
      increased. CONCLUSIONS: Mice with deficiency in adaptive immunity are obese,
      partly owing to decreased energy expenditure, but are metabolically normal,
      suggesting that mature lymphocytes have necessary roles in the development of
      obesity-related metabolic dysregulation.

PMID- 25994807
TI  - Molecular Genetics of Sex Identification, Breed Ancestry and Polydactyly in the
      Norwegian Lundehund Breed.
AB  - The Norwegian Lundehund breed of dog has undergone a severe loss of genetic
      diversity as a result of inbreeding and epizootics of canine distemper. As a
      consequence, the breed is extremely homogeneous and accurate sex identification
      is not always possible by standard screening of X-chromosomal loci. To improve
      our genetic understanding of the breed we genotyped 17 individuals using a genome
      wide array of 170 000 single nucleotide polymorphisms (SNPs). Standard analyses
      based on expected homozygosity of X-chromosomal loci failed in assigning
      individuals to the correct sex, as determined initially by physical examination
      and confirmed with the Y-chromosomal marker, amelogenin. This demonstrates that
      identification of sex using standard SNP assays can be erroneous in highly inbred
      individuals. 

PMID- 25994808
TI  - Medical Systemic Therapies for Hepatocellular Carcinoma: Clinical Perspectives
      and Safety Profile.
AB  - A multidisciplinary approach based on clinical expertise and knowledge of
      molecular processes involved in hepatocarcinogenesis is needed for the proper
      management of hepatocellular carcinoma (HCC) patients. Such information must be
      considered in the context of pathobiology of the underlying liver disease. New
      drugs targeting specific molecular steps in pathways involved in HCC growth and
      development bear the promise to radically modify the pharmacological therapies
      currently in use in hepatooncology. Sorafenib was the first drug approved in the
      setting of advanced HCC, but although it produces some improvement in survival,
      the responses are not durable. In addition, there are significant side effects.
      Other angiogenesis inhibitors are in development to treat HCC both in the first
      line setting and after progression following sorafenib failure; among them,
      tivantinib, an inhibitor of cMET receptor, showed interesting results in a recent
      phase-II study. Additional agents currently studied for the treatment of HCC
      patients are briefly examined in this review. Aim of this paper is to discuss the
      state of the art in the management of advanced HCC patients, with a particular
      interest for the description of their side effects. 

PMID- 25994809
TI  - Kinetic Model of Photoautotrophic Growth of Chlorella sp. Microalga, Isolated
      from the Setubal Lagoon.
AB  - In this work, a kinetic expression relating light availability in the culture
      medium with the rate of microalgal growth is obtained. This expression, which is
      valid for low illumination conditions, was derived from the reactions that take
      part in the light-dependent stage of photosynthesis. The kinetic expression
      obtained is a function of the biomass concentration in the culture, as well as of
      the local volumetric rate of absorption of photons, and only includes two
      adjustable parameters. To determine the value of these parameters and to test the
      validity of the hypotheses made, autotrophic cultures of the Chlorella sp. strain
      were carried out in a modified BBM medium at three CO2 concentrations in the gas
      stream, namely 0.034%, 0.34% and 3.4%. Moreover, the local volumetric rate of
      photon absorption was predicted based on a physical model of the interaction of
      the radiant energy with the suspended biomass, together with a Monte Carlo
      simulation algorithm. The proposed intrinsic expression of the biomass growth
      rate, together with the Monte Carlo radiation field simulator, are key to scale
      up photobioreactors when operating under low irradiation conditions,
      independently of the configuration of the reactor and of its light source. 

PMID- 25994810
TI  - Does the Implementation of an Advanced Life Support Quick Response Vehicle (QRV)
      in an Integrated Fire/EMS System Improve Patient Contact Response Time?
AB  - BACKGROUND: The current Fire/Emergency Medical Services (EMS) model throughout
      the United States involves emergency vehicles which respond from a primary
      location (ie, firehouse or municipal facility) to emergency calls. Quick response
      vehicles (QRVs) have been used in various Fire/EMS systems; however, their
      effectiveness has never been studied. OBJECTIVES: The goal of this study was to
      determine if patient response times would decrease by placing an Advanced Life
      Support (ALS) QRV in an integrated Fire/EMS system. METHODS: Response times from
      an integrated Fire/EMS system with an annual EMS call volume of 3,261 were
      evaluated over the three years prior to the implementation of this study. For a 2
      month period, an ALS QRV staffed by a firefighter/paramedic responded to
      emergency calls during peak call volume hours of 8:00 am to 5:00 pm. The staging
      of this vehicle was based on historical call volume percentages using respective
      geocodes as well as system requirements during multiple emergency dispatches.
      RESULTS: Prior to the study, the citywide average response time for the twelve
      months preceding was 5.44 minutes. During the study, the citywide average
      response time decreased to 4.09 minutes, resulting in a 27.62% reduction in
      patient response time. CONCLUSION: The implementation of an ALS QRV in an
      integrated Fire/EMS system reduces patient response time. Having a QRV that is
      not staged continuously in a traditional fire station or municipal location
      reduces the time needed to reach patients. Also, using predictive models of
      historic call volume can aid Fire and EMS administrators in reduction of call
      response times.

PMID- 25994811
TI  - Attenuation of radiation-induced gastrointestinal damage by epidermal growth
      factor and bone marrow transplantation in mice.
AB  - PURPOSE: We examined the effect of epidermal growth factor (EGF) and bone marrow
      transplantation (BMT) on gastrointestinal damage after high-dose irradiation of
      mice. MATERIAL AND METHODS: C57Black/6 mice were used. Two survival experiments
      were performed (12 and 13 Gy; (60)Co, 0.59-0.57 Gy/min). To evaluate BMT and EGF
      action, five groups were established - 0 Gy, 13 Gy, 13 Gy + EGF (at 2 mg/kg,
      first dose 24 h after irradiation and then every 48 h), 13 Gy + BMT (5 * 10(6)
      cells from green fluorescent protein [GFP] syngenic mice, 4 h after irradiation),
      and 13 Gy + BMT + EGF. Survival data, blood cell counts, gastrointestine and
      liver parameters and GFP positive cell migration were measured. RESULTS: BMT and
      EGF (three doses, at 2 mg/kg, administered 1, 3 and 5 days after irradiation)
      significantly increased survival (13 Gy). In blood, progressive cytopenia was
      observed with BMT, EGF or their combination having no improving effect early
      after irradiation. In gastrointestinal system, BMT, EGF and their combination
      attenuated radiation-induced atrophy and increased regeneration during first week
      after irradiation with the combination being most effective. Signs of systemic
      inflammatory reaction were observed 30 days after irradiation. CONCLUSIONS: Our
      data indicate that BMT together with EGF is a promising strategy in the treatment
      of high-dose whole-body irradiation damage.

PMID- 25994813
TI  - Hematological aftermath of the radiation accident in Istanbul.
AB  - PURPOSE: The effects of radiation exposure are long-lasting. Long-term monitoring
      is imperative to diagnose late effects and improve our far-sightedness about
      possible events in the future. A radiation accident occurred in Istanbul in 1998
      that resulted in mild to moderate acute radiation syndrome (ARS). In this study
      we aimed to investigate the changes in hematological parameters at the long-term
      follow-up of ARS patients. METHODS: Ten adults were hospitalized after exposure
      to a 60Co source. Seven were diagnosed as having ARS and had severe and
      symptomatic pancytopenia. All of the exposed people recovered following intensive
      treatment. Treatment was supportive with transfusion, granulocyte-colony
      stimulating factor, and anti- infective management covering antifungal agents.
      Patients were closely monitored. Nine years after the accident, the initial and
      follow-up complete blood count examinations and peripheral blood smears (PBS)
      were comparatively evaluated by an experienced hematologist. The hematological
      laboratory values of the patients on admission, after treatment, and nine years
      after the accident were documented and compared. RESULTS: Biodosimetric analysis
      revealed that whole-body doses ranged from 1-1.9 Gy. All subjects have shown
      complete recovery of the hematological laboratory values after treatment. All but
      one of the subjects showed complete blood cell recovery. The improvement of the
      blood cell count of the excepted patient stalled at a mildly reduced level and
      his bone marrow was still hypocellular nine years after the accident; however, no
      malignant changes were detected. Values at admission were significantly different
      compared with post treatment and present values of all patients. Post treatment
      and follow-up values were similar. One of the patients died of lung cancer. None
      of the patients developed hematological malignancy. CONCLUSIONS: In this study,
      the recovery from ARS was complete after treatment. The small population, short
      follow-up period, and the relatively small doses resulted in no long-term adverse
      effects, as would be predicted.

PMID- 25994812
TI  - Combined immunomodulator and antimicrobial therapy eliminates polymicrobial
      sepsis and modulates cytokine production in combined injured mice.
AB  - PURPOSE: A combination therapy for combined injury (CI) using a non-specific
      immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A
      (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin
      (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine
      production. MATERIALS AND METHODS: Female B6D2F(1)/J mice received 9.75 Gy cobalt
      60 gamma-radiation and wound. Bacteria were isolated and identified in three
      tissues. Incidence of bacteria and cytokines were compared between treatment
      groups. RESULTS: Results demonstrated that the lethal dose for 50% at 30 days
      (LD(50/30)) of B6D2F(1)/J mice was 9.42 Gy. Antimicrobial therapy increased
      survival in radiation-injured (RI) mice. Combination therapy increased survival
      after RI and extended survival time but did not increase survival after CI.
      Sepsis began five days earlier in CI mice than RI mice with Gram-negative species
      predominating early and Gram-positive species increasing later. LVX plus AMX
      eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria
      in CI and most RI mice but not Gram-negative. Treatments significantly modulated
      12 cytokines tested, which pertain to wound healing or elimination of infection.
      CONCLUSIONS: Combination therapy eliminates infection and prolongs survival time
      but does not assure CI mouse survival, suggesting that additional treatment for
      proliferative-cell recovery is required.

PMID- 25994814
TI  - Comparison of nedaplatin-based versus cisplatin-based chemotherapy for advanced
      non-small cell lung cancer among East Asian populations: A meta-analysis.
AB  - Whether nedaplatin and cisplatin are equally effective for advanced non-small
      cell lung cancer (NSCLC) remains uncertain. Therefore, we performed a meta
      analysis of trials to compare nedaplatin-based chemotherapy with cisplatin-based
      chemotherapy. We conducted a literature search to identify trials that had
      investigated the substitution of nedaplatin for cisplatin in the treatment of
      advanced NSCLC. Fourteen randomized controlled trials were included. We found
      equivalent overall response, overall survival, and survival probability (0.5
      year, 1-year). Considering the toxicity profiles, nausea and vomiting were common
      in the cisplatin group (OR = 0.28, 95% CI = 0.20-0.40, P < 0.001), whereas severe
      thrombocytopenia was common in the nedaplatin group (OR = 1.68, 95% CI = 1.18
      2.40, P = 0.005). A subgroup analysis of grades 1-4 nephrotoxicity showed that
      cisplatin-based chemotherapy resulted in more renal toxicity (OR = 0.40, 95% CI =
      0.24-0.68, P = 0.001). No significant heterogeneity and publication bias were
      observed. Cumulative analysis found a stable time-dependent trend. Consistent
      results stratified by age, regimen, and country were observed. Cisplatin-based
      chemotherapy was associated with non-inferior antitumor efficacy compared with
      nedaplatin-based therapy. Therefore, the toxicity profile might play an important
      role in choosing between cisplatin-based or nedaplatin-based regimens.

PMID- 25994817
TI  - Calcification of decellularized and alpha-galactosidase-treated bovine
      pericardial tissue in an alpha-Gal knock-out mouse implantation model: comparison
      with primate pericardial tissue.
AB  - OBJECTIVES: Immune reaction against the alpha-Gal(Galalpha1,3-Galbeta1-4GlcNAc-R)
      epitope is known to be one of the important factors for calcification of
      bioprostheses. The genetically manipulated alpha-Gal knock-out (KO) mice lacking
      the alpha-Gal epitope and containing anti-alpha-Gal antibodies may simulate an
      immune response against xenoantigens in primates including humans. The aims of
      this study were (i) to compare calcification and immune reactions of
      glutaraldehyde (GA)-fixed bovine with primate pericardium and (ii) to assess the
      differences in bovine pericardium treated with decellularization and alpha
      galactosidase, using an alpha-Gal KO mouse implantation model. METHODS: Four
      types of GA-fixed xenogeneic tissues were implanted into alpha-Gal KO mice for 16
      weeks (Group 1: primate pericardium, n = 14; Group 2: bovine pericardium, n = 19;
      Group 3: decellularized bovine pericardium, n = 20; Group 4: decellularized and
      alpha-galactosidase-treated bovine pericardium, n = 21). Serum enzyme-linked
      immunosorbent assays for immune response were performed before implantation and
      2, 4, 8, 12 and 16 weeks after implantation. Implanted tissues were harvested and
      studied for histopathology and quantification of calcification. RESULTS: Anti
      alpha-Gal IgG antibody titres of Groups 2-4 increased after implantation although
      the titres did not change in Group 1. When compared with preimplantation titres,
      the increased IgG titres were highest at 8 weeks after implantation in Groups 2-4
      (0.4358 +/- 0.0524 vs 0.5462 +/- 0.0519 in Group 2, 0.4712 +/- 0.0500 vs 0.6424
      +/- 0.0613 in Group 3 and 0.4892 +/- 0.0801 vs 0.6112 +/- 0.0339 in Group 4; P =
      0.028 in each group). Median calcium levels were higher in Group 2 than in Group
      1 (9.21 vs 3.86 MUg/mg, P < 0.001), but were not significantly higher in Groups 3
      and 4 than in Group 1 (4.09 MUg/mg in Group 3, P = 0.904; 5.47 MUg/mg in Group 4,
      P = 0.210). CONCLUSIONS: GA-fixed bovine pericardium showed higher calcium levels
      than primate pericardium. Increased IgG antibody titres in the bovine but not in
      the primate group suggested that an immune response was involved in implanted
      tissue. Differences in calcium levels of bovine pericardium treated with
      decellularization and alpha-galactosidase were insignificant compared with
      primate pericardium, suggesting those treatments to be effective methods in
      preventing calcification of the bioprostheses.

PMID- 25994816
TI  - Gene variants associated with age at menopause are also associated with
      polycystic ovary syndrome, gonadotrophins and ovarian volume.
AB  - STUDY QUESTION: Is there a relationship between the genetic risk for polycystic
      ovary syndrome (PCOS) and genetic variants that influence timing of menopause?
      SUMMARY ANSWER: The genetic risk score, which sums the contribution of variants
      at all menopause loci, was associated with PCOS. WHAT IS ALREADY KNOWN: Ovarian
      parameters and anti-Mullerian hormone levels suggest that women with PCOS should
      have a later age at menopause. STUDY DESIGN, SIZE, DURATION: The study was a case
      control examination of genetic variants associated with age at menopause in a
      discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston
      recruited from 2003 to 2012. Replication was performed in women from Greece
      (cases, n = 884 and controls, n = 311). PARTICIPANTS/MATERIALS, SETTINGS,
      METHODS: PCOS was defined by the National Institutes of Health criteria in Boston
      and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria
      (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n =
      101). Controls in Boston and Greece had regular menstrual cycles and no
      hyperandrogenism. Allele frequencies for variants previously associated with age
      at menopause were examined in PCOS cases and controls, along with the
      relationship to quantitative traits. MAIN RESULTS AND ROLE OF CHANCE: The variant
      rs11668344-G was associated with decreased risk of PCOS (odds ratio: 0.77 [0.59
      0.93]; P = 0.004). There was a strong relationship between the late menopause
      allele rs12294104-T and increased LH levels (beta +/- SE; 0.26 +/- 0.06; P = 5.2
      * 10(-5)) and the LH:FSH ratio (0.28 +/- 0.06; P = 2.7 * 10(-6)). The minor
      allele at rs10852344-T was associated with smaller ovarian volume (-0.16 +/-
      0.05; P = 0.0012). A genetic risk score calculated from 16 independent variants
      associated with age at menopause was also associated with PCOS (P < 0.02), LH and
      the LH:FSH ratio (both P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The variant
      rs11668344 was not associated with PCOS in the Greek cohort, but results
      exhibited the same direction of effect as the Boston cohort. However, it is
      possible that the individual association was a false positive in the Boston
      cohort. WIDER IMPLICATIONS OF THE FINDINGS: The study demonstrates that gene
      variants known to influence age at menopause are also associated with risk for
      PCOS. Further, our data suggest that the relationship between age at menopause
      and PCOS may be explained, at least in part, by effects on LH levels and follicle
      number. The data point to opposing influences of the genetic variants on both
      menopausal age and PCOS. STUDY FUNDING/COMPETING INTERESTS: The project was
      supported by award number R01HD065029 from the Eunice Kennedy Shriver National
      Institute of Child Health & Human Development, award number 1 UL1 RR025758,
      Harvard Clinical and Translational Science Center, from the National Center for
      Research Resources and award 1-10-CT-57 from the American Diabetes Association.
      C.K.W. is a consultant for Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER:
      NCT00166569.

PMID- 25994818
TI  - Prelinguistic Relational Concepts: Investigating Analogical Processing in
      Infants.
AB  - This research asks whether analogical processing ability is present in human
      infants, using the simplest and most basic relation-the same-different relation.
      Experiment 1 (N = 26) tested whether 7- and 9-month-olds spontaneously detect and
      generalize these relations from a single example, as previous research has
      suggested. The attempted replication failed. Experiment 2 asked whether infants
      could abstract the relation via analogical processing (Experiment 2, N = 64).
      Indeed, with four exemplars, 7- and 9-month-olds could abstract the same
      different relation and generalize it to novel pairs. Furthermore, prior
      experience with the objects disrupted learning. Facilitation from multiple
      exemplars and disruption by individual object salience are signatures of
      analogical learning. These results indicate that analogical ability is present by
      7 months.

PMID- 25994819
TI  - Existing joint erosions increase the risk of joint space narrowing independently
      of clinical synovitis in patients with early rheumatoid arthritis.
AB  - INTRODUCTION: Clinical synovitis is often associated with damage to bone and
      cartilage. Previous data have suggested that joint erosions (JE) are more
      prevalent than joint space narrowing (JSN) and that the two processes are partly
      independent of each other. The objective of this study was to evaluate whether
      the presence of JE in an individual joint can lead to development of JSN and if
      existing JSN leads to new onset of JE, in the absence of synovitis. METHODS: The
      Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled,
      Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFalpha Antibody
      Adalimumab Given Every Second Week With Methotrexate Given Weekly and the
      Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients
      With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis
      (RA) patients who were randomized to one of three treatments: methotrexate (MTX),
      adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at
      26 and 52 weeks and synovitis assessments from week 26 to 52 were included.
      Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26
      and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time
      and sequence, scored 14 bilateral joints individually for JE and JSN.
      Multivariate logistic modeling was used to characterize the dependence of JE/JSN
      onset at 52 weeks. Analyses were performed based on treatment arm and were also
      performed within individual joints. RESULTS: JE and swelling were independently
      and comparably associated with onset of JSN at week 52. Assessment by individual
      joints indicated that existing JE, independent of swelling, was significantly
      associated with JSN onset in higher proportions of metatarsophalangeal (MTP;
      7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10)
      joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its
      ability to suppress synovitis and limits JE/JSN onset and progression in joints
      with existing damage. CONCLUSIONS: Existing JE predisposes individual joints to
      development of JSN independently of synovitis in the same joint. Weight-bearing
      MTP joints with JE may be at increased risk for JSN when compared with MCPs and
      PIPs. TRIAL REGISTRATION: Clinicaltrials.gov NCT00195663. Registered 13 September
      2005.

PMID- 25994821
TI  - [Indoleamine 2,3-dioxygenase in oncology and psychiatry].
AB  - In the last years an attention has been paid to the indoleamine 2,3-dioxygenase
      (IDO), an enzyme catabolising L-tryptophan to kynurenine. Growing evidence has
      been accumulated that kynurenine and other metabolites of tryptophan play an
      important role in the pathogenesis of malignant tumours and some neurological and
      psychiatric disorders. The gradual recognition of mechanisms operative in their
      development may help to identify etiological factors involved and becomes
      prerequisite for the progress in their diagnostics and therapy. In oncology,
      great effort is directed to the development and testing of substances inhibiting
      IDO activity. It is expected that some of them will be utilized in the
      immunotherapy of cancer. In the field of psychiatric disorders, namely in
      schizophrenia and depression, the role of IDO is linked to immune dysregulation.
      In those diseases, IDO represents a potential mediator between immunological
      reactivity and alterations of the brain function. Changes in the IDO activity may
      also mediate interaction between the genetic predisposition and environmental
      factors. 

PMID- 25994820
TI  - The utility of human fallopian tube mucosa as a novel source of multipotent stem
      cells for the treatment of autologous reproductive tract injury.
AB  - INTRODUCTION: Fallopian tube, which is normally discarded in surgical procedures,
      has proven to be a source of mesenchymal stem cells (MSCs) with increasing
      evidence. However, fallopian tube mucosa, which can be acquired via non-invasive
      procedures, is a previously unknown source of MSCs. In the present study, we
      explored the existence of MSCs in the human fallopian tube mucosa and also
      compared multipotent stem cells derived from fallopian tubes and fallopian tube
      mucosa according to their biological characteristics and therapeutic potential
      for treatment of autologous reproductive tract injury. METHODS: Cells isolated
      from human fallopian tubes and fallopian tube mucosa were expanded and
      characterised by flow cytometry. The proliferative capacity of both cell types
      was measured by performing colony-forming unit-fibroblast and Cell Counting Kit-8
      assays. Both cell types underwent in vitro adipogenic, chondrogenic, and
      osteogenic differentiation. The expression of osteocyte-, adipocyte-, and
      chondrocyte-related genes in the differentiated cell lineages was assessed by
      reverse transcription-polymerase chain reaction. The secretion of growth factors
      and immunomodulatory cytokines by both cell types were measured by enzyme-linked
      immunosorbent assays. RESULTS: We found that MSCs existed in the fallopian tube
      mucosa. The comparison between human fallopian tube MSCs (hFTMSCs) and human
      fallopian tube mucosa MSCs (hFMMSCs) showed that hFTMSCs had a stronger
      proliferative capacity and shorter duplication time than hFMMSCs. Both cell types
      could be differentiated into adipocytes, osteoblasts, or chondrocytes in vitro.
      Real-time polymerase chain reaction analysis demonstrated that hFTMSCs displayed
      increased expression of osteogenic-specific genes compared with hFMMSCs, but the
      two types of cells showed no significant increase in the mRNA expression of
      adipogenic-specific or chondrogenic-specific genes. hFMMSCs and hFTMSCs robustly
      produced a variety of growth factors and immunomodulatory cytokines. CONCLUSIONS:
      Human fallopian tube mucosa is a novel source of multipotent cells. hFMMSCs
      demonstrated stronger proliferative capacity and superior secretion of growth
      factors and immunomodulatory cytokines than hFTMSCs, making the former a better
      source of stem cells for the treatment of autologous reproductive tract injury.
      Compared with fallopian tube, fallopian tube mucosa has more wide-ranging
      applications and can be used to carry out autologous transplantation.

PMID- 25994822
TI  - [Anal fissure].
AB  - Anal fissure is one of the very frequent and painful proctologic diseases. Linear
      ulcer is situated in the anal canal and extending from the dentate line to the
      margin of the anus. Fissure can cause pain and bleeding. Diagnosis is made from
      the history and local inspection. Acute anal fissure should be treated
      conservatively - increased fibre and fluid intake, warm baths, local anaesthetic
      ointment, alternatively with nitrates and if all else fails by botulinum toxin.
      Treatment of chronic fissure will start conservatively but operative options are
      necessary in many cases. 

PMID- 25994823
TI  - [Subcutaneous rehydration in patients in terminal phase of dementia].
AB  - BACKGROUND: Dehydration among seniors is not rare. It is both medical and nursing
      problem, leading to many complications. Attention is paid to ways of rehydration
      among seniors in terminal phase of dementia. Aim to evaluate frequency of
      complications due to subcutaneous rehydration in patients with terminal phase of
      dementia and to evaluate nurses opinion in relation to this method of
      rehydration. METHODS: Observational study has been designed in women
      psychogeriatric wards, Mental hospital Kromeriz, from June 2012 - December 2013,
      evaluating frequency of complications due to subcutaneous rehydration - local
      oedema, local infection, local erythema (60 patients group) and evaluating nurses
      opinion in relation to this method of rehydration (18 nurses group). METHODS:
      observation, interview. RESULTS: No complications of subcutaneous dehydration was
      found in 58 cases (96.6%), in 1 case local oedema (1.7%) and in 1 case (1.7%)
      local erythema manifested. Nurses reported effortles-sness of subcutaneous
      rehydration together with sparing of their working time and comfort to a patient
      in comparison with intravenous rehydration therapy. CONCLUSION: Subcutaneous
      rehydration seems to be an appropriate method of rehydration in patients with
      terminal phase of dementia.

PMID- 25994824
TI  - [With children against obesity].
AB  - The project "With Children Against Obesity" (www.sdetmiprotiobezite.cz) is an
      original and innovative prevention website, which is currently unparalleled in
      the Czech Republic. It is a rare project that deals not only with the issue of
      childhood obesity for the general public but also for professionals. The website
      offers a comprehensive view of the prevention and treatment of overweight and
      obese children. The project offers original products that can be used in the
      everyday clinical practice for specific individuals with risks of developing
      obesity, including their family background. It follows the basic principles of
      prevention of metabolic diseases. 

PMID- 25994825
TI  - [Contribution to the history of pharmacology (the late antique period)].
AB  - Pharmacological literature in the Late Antique period followed the Roman
      tradition and widely used Scribonius Largus and excerpts from the writings of
      Pliny the Elder. Literature was created both in the western part of the Roman
      Empire and in North Africa in Carthage. Manuals have been written about medicinal
      plants (Herbarius of Pseudo-Apuleius, De herba vettonica of Pseudo-Musa), for
      drugs obtained from the animal kingdom (Liber medicinae of Sextus Placitus) or
      documents containing both (De medicina of Cassius Felix, De medicamentis of
      Marcellus Empiricus). The contribution of this literature is the mediation of
      ancient knowledge into the Middle Ages. 

PMID- 25994826
TI  - [Double jubilee of undervalued professor J. D. John].
AB  - Paper draws attention to an interesting personality of a professor of medical
      police and forensic medicine, overlooked by historians. This year 250 years has
      passed since his birth and 200 years since his death. Professor Johns biography
      is given and his work appraised. 

PMID- 25994827
TI  - Incidental oesophageal leiomyoma during laparoscopic Roux-en-Y gastric bypass:
      finding the unexpected does not affect outcomes.
AB  - Most bariatric procedures are now performed laparoscopically. Here, we describe a
      case of incidental oesophageal leiomyoma found during laparoscopic Roux-en-Y
      gastric bypass (LRYGB). To our knowledge, this is the first such case reported.
      Our patient was admitted for an elective LRYGB. She had no upper gastrointestinal
      symptoms, and therefore did not undergo preoperative oesophagogastroduodenoscopy
      (OGD). During surgery, a hiatus hernia and an incidental oesophageal leiomyoma
      were found and treated with hernia repair and enucleation. The end outcome was
      unaffected. We were able to concomitantly treat the unexpected finding of an
      oesophageal leiomyoma and a hiatus hernia during the LRYGB. The routine use of
      OGD prior to bariatric surgery is still controversial. While surgeons should be
      prepared for unexpected pathologies, when performing laparoscopic bariatric
      surgery, a routine OGD prior to LRYGB is probably not necessary in asymptomatic
      patients. Laparoscopic enucleation of oesophageal leiomyoma during LRYGB is
      feasible and safe. 

PMID- 25994829
TI  - Wire Passages of 0.035-inch Looped Wire Technique for Femoropopliteal Long Total
      Occlusions.
AB  - AIM: Although it is understood that a looped wire technique using a 0.035-inch
      wire for femoropopliteal (FP) long chronic total occlusions (CTOs) goes to the
      subintima, there has been no systematic assessment of wire passages. The purpose
      of this study is to examine these passages by intravascular ultrasound (IVUS)
      after looped wire technique for FP long CTOs. METHODS: Between March 2012 and
      October 2014, 57 consecutive FP long CTO lesions (mean lesion length, 246 +/- 42
      mm), involving the superficial femoral artery ostium and treated with IVUS-guided
      endovascular therapy, were enrolled. After IVUS confirmed that the initial wire
      passage was intraplaque, the looped wire technique was routinely conducted
      through the CTO body. Based on IVUS findings, the wire passage was classified
      into 3 types: intraplaque, subintimal, and intramedia. RESULTS: At the FP lesion
      in the proximal, middle, and distal segments, the wire proceeded intraplaque in
      98%, 25%, and 20% cases; subintimal in 2%, 61%, and 52%; and intramedia in 0%,
      14%, and 28%, respectively. The success rate of antegrade wiring was 74%, with
      the remaining 26% cases requiring an additional retrograde approach. CONCLUSIONS:
      The looped wire technique variably proceeds to intraplaque, subintimal, or
      intramedia, even starting from intraplaque in FP long CTOs.

PMID- 25994828
TI  - The Association Between the Cardio-ankle Vascular Index and Other Parameters of
      Vascular Structure and Function in Caucasian Adults: MARK Study.
AB  - AIM: We assessed whether there is an association between the cardio-ankle
      vascular index (CAVI) score and the carotid intima media thickness (IMT), the
      pulse wave velocity (PWV) and the central augmentation index (CAIx) that is
      independent of the subject's cardiovascular risk and pharmacological treatment.
      METHODS: The CAVI score was measured in 500 subjects using a VaSera device and
      the brachial ankle PWV (ba-PWV) was calculated. A carotid ultrasound was used to
      measure the IMT. A Mobil-O-Graph device was used to measure the carotid femoral
      PWV (cf-PWV) and the CAIx. The Framingham-D'Agostino and SCORE scales were used
      to measure the subject's cardiovascular risk. RESULTS: The mean value of the CAVI
      score was 8.59 +/- 1.1. IMT, CAIx and PWV maintained a positive association with
      the CAVI score (p < 0.01) in a multiple linear regression analysis, after
      adjusting for the subject's cardiovascular risk, body mass index and
      pharmacological treatment. The cut-off level that gave the maxima sensitivity and
      specificity to detect a mean IMT of > 0.90 mm was 8.95 (AUC=0.67) for the CAVI
      score, 8.85 (AUC=0.66) for cf-PWV and 15.10 (AUC=0.66) for ba-PWV. The cut-off to
      detect a maxima IMT of > 0.90 mm was 8.60 (AUC=0.62) for the CAVI score, 8.85
      (AUC=0.64) for cf-PWV and 15.75 (AUC=0.70) for ba-PWV. CONCLUSION: There was a
      positive association of the CAVI score with vascular structure and function
      parameters that was independent of cardiovascular risk and any medications being
      used by the subject. The ability of the CAVI score to predict carotid
      atherosclerosis is similar to that of cf-PWV and ba-PWV in Caucasian adults.

PMID- 25994830
TI  - Preservation of Glucagon-Like Peptide-1 Level Attenuates Angiotensin II-Induced
      Tissue Fibrosis by Altering AT1/AT 2 Receptor Expression and Angiotensin
      Converting Enzyme 2 Activity in Rat Heart.
AB  - PURPOSE: The glucagon-like peptide-1 (GLP-1) has been shown to exert
      cardioprotective effects in animals and patients. This study tests the hypothesis
      that preservation of GLP-1 by the GLP-1 receptor agonist liraglutide or the
      dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin is associated with a
      reduction of angiotensin (Ang) II-induced cardiac fibrosis. METHODS AND RESULTS:
      Sprague-Dawley rats were subjected to Ang II (500 ng/kg/min) infusion using
      osmotic minipumps for 4 weeks. Liraglutide (0.3 mg/kg) was subcutaneously
      injected twice daily or linagliptin (8 mg/kg) was administered via oral gavage
      daily during Ang II infusion. Relative to the control, liraglutide, but not
      linagliptin decreased MAP (124 +/- 4 vs. 200 +/- 7 mmHg in control, p < 0.003).
      Liraglutide and linagliptin comparatively reduced the protein level of the Ang II
      AT1 receptor and up-regulated the AT2 receptor as identified by a reduced AT1/AT2
      ratio (0.4 +/- 0.02 and 0.7 +/- 0.01 vs. 1.4 +/- 0.2 in control, p < 0.05),
      coincident with the less locally-expressed AT1 receptor and enhanced AT2 receptor
      in the myocardium and peri-coronary vessels. Both drugs significantly reduced the
      populations of macrophages (16 +/- 6 and 19 +/- 7 vs. 61 +/- 29 number/HPF in
      control, p < 0.05) and alpha-SMA expressing myofibroblasts (17 +/- 7 and 13 +/- 4
      vs. 66 +/- 29 number/HPF in control, p < 0.05), consistent with the reduction in
      expression of TGFbeta1 and phospho-Smad2/3, and up-regulation of Smad7.
      Furthermore, ACE2 activity (334 +/- 43 and 417 +/- 51 vs. 288 +/- 19 RFU/min/MUg
      protein in control, p < 0.05) and GLP-1 receptor expression were significantly up
      regulated. Along with these modulations, the synthesis of collagen I and tissue
      fibrosis were inhibited as determined by the smaller collagen-rich area and more
      viable myocardium. CONCLUSION: These results demonstrate for the first time that
      preservation of GLP-1 using liraglutide or linagliptin is effective in inhibiting
      Ang II-induced cardiac fibrosis, suggesting that these drugs could be selected as
      an adjunctive therapy to improve clinical outcomes in the fibrosis-derived heart
      failure patients with or without diabetes.

PMID- 25994831
TI  - Metabolic Syndrome: Does it Differ Between Women and Men?
AB  - Cardiovascular disease represents a massive healthcare burden worldwide. Gender
      differences in the pathophysiology, presentation and prognosis of cardiovascular
      disease have been described in the literature. Metabolic syndrome, characterized
      by a cluster of metabolic abnormalities is associated with increased risk for
      type 2 diabetes mellitus and atherosclerotic cardiovascular disease. With the
      global obesity epidemic, the prevalence of metabolic syndrome is rising rapidly
      in the developed as well as developing world. However, there is considerable
      variation in the prevalence based on geography, age, sex and, definition used for
      diagnosis. Data on gender related differences in metabolic syndrome is relatively
      scarce. Here, we aim to review the gender differences in epidemiology and
      pathophysiology of metabolic syndrome as well as its individual components.
      Knowledge of gender differences in metabolic syndrome can help design gender
      specific preventative and therapeutic strategies that will have a positive impact
      on overall population health. 

PMID- 25994832
TI  - Distraction osteogenesis and arthrodesis as a new surgical option for
      chondrosarcoma in the distal tibia.
AB  - Recent advances in the management of bone tumors have led to a significant
      increase in the survival rates of patients with malignant bone tumors. Thus, limb
      salvage surgery has gained importance for preserving limb function in the
      management of bone tumors. However, surgery presents unique difficulties in terms
      of the biomechanics and obtaining a soft-tissue cover, such as when the ankle is
      involved in the primary malignant bone tumor. We report a case of chondrosarcoma
      of the distal tibia treated with wide en bloc resection arthrodesis and
      reconstruction of the defect using distraction osteogenesis, which offers an
      effective alternative protocol for limb salvage. The patient has remained disease
      free for 3 years since the initial surgery and can maintain normal limb athletic
      function.

PMID- 25994833
TI  - Factors Affecting the Outcomes of Uncomplicated Primary Open Ankle Arthrodesis.
AB  - BACKGROUND: The objective of this study was to identify factors influencing
      operative outcomes in straightforward, uncomplicated open ankle fusions. METHODS:
      We reviewed all primary open ankle fusions conducted at 1 institution over an 11
      year period to identify straightforward, uncomplicated open ankle fusions.
      Inclusion required a minimum of 6 months follow-up. Patients were excluded for
      neuropathic arthropathy, insensate limb, failed total ankle replacement,
      simultaneous arthrodesis of the subtalar joint, or fusions performed within 1
      year of injury to salvage failed fixation and painful function due to (1) open
      fractures, (2) segmental bone loss greater than 1 cm, (3) infection, or (4) talar
      body fractures. The primary outcome variable was radiographic union at 6 months.
      Other operative complications were analyzed as secondary outcomes. Five hundred
      twenty-eight ankle fusion surgeries were performed on 440 patients at 1
      institution during the study period. Two hundred fifteen surgeries met
      inclusion/exclusion eligibility criteria for uncomplicated open ankle fusions.
      RESULTS: The overall union rate was 91%. In this cohort of uncomplicated open
      ankle fusions, bivariate analysis over a broad range of potential factors and
      further focused multivariate analysis found that nonunion was more than 3 times
      more likely to occur after previous subtalar fusion, and 2 times more likely to
      occur in patients with preoperative varus ankle alignment. The rate of
      reoperation was 19%, with nonunion revision as the leading reason, followed by
      hardware removal and incision and drainage for presumed infection. Diabetes was
      not a significant risk factor of either deep or superficial infection.
      CONCLUSION: Open ankle fusion failed in 9% of uncomplicated ankles with
      arthritis. Patients who had an open ankle fusion done after previous subtalar
      joint fusion, as well as those who had preoperative varus ankle alignment, had a
      significantly higher rate of nonunion. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 25994834
TI  - Numb Expression Contributes to the Maintenance of an Undifferentiated State in
      Human Epidermis.
AB  - The epidermis is a stratified epithelium with a stem cell subpopulation in the
      basal layer that constantly replicates and periodically detaches from the base,
      undergoing a differentiation process that involves various developmental signals
      and regulatory pathways. During the last 10 years, a number of studies tried to
      elucidate the intricate scenario that maintains the epithelial shield during the
      entire life span. In our study, we investigated the role of Numb in the skin
      compartment and, in particular, its involvement in stem cell maintenance. Numb
      expression in the skin compartment was assessed by immunofluorescence and
      immunohistochemistry analysis. We evaluated Numb expression in primary epithelial
      cells at various differentiative stages. Moreover, we overexpressed Numb in the
      isolated population enriched for undifferentiated progenitors to establish its
      involvement in in vitro differentiation. We demonstrated that Numb in high
      proliferating epithelial undifferentiated progenitors contributes to the
      maintenance of an undifferentiated state. This regulation involves the E3 ligases
      Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed
      that Numb is highly expressed in squamous cell carcinoma (SCC), where we observed
      a direct correlation between the expression of Numb and Ki-67. Our data indicate
      for the first time that Numb is involved in the maintenance of the
      undifferentiated proliferating stem cell pool in the epithelial basal layer and
      its expression could become a new marker in skin cancer. 

PMID- 25994835
TI  - Convenient recycling of 3D AgX/graphene aerogels (X = Br, Cl) for efficient
      photocatalytic degradation of water pollutants.
AB  - 3D AgX/graphene aerogel (GA) composites (X = Br, Cl) are synthesized. Not only is
      the photocatalytic performance increased in comparison with pristine AgX, but
      also the photocatalytic cycling process is facilitated just using tweezers Thus,
      the comprehensive performance of the AgX/GA composites provides robust support
      for future industrial applications of the photocatalyst. 

PMID- 25994836
TI  - Distinguishing Foeniculum vulgare fruit from two adulterants by combination of
      microscopy and GC-MS analysis.
AB  - Foeniculum vulgare fruit (FVF) is a widely used traditional medicine. However,
      two adulterants, namely Anethum graveolens fruit (AGF) and Cuminum cyminum fruit
      (CCF), have been found in use as FVF in China owing to similar appearance and
      odor. For the purpose of accurate differentiation of the three herbal medicines,
      extensive anatomical examination and chemical profiling were conducted. Using
      light microscopy and fluorescence microscopy, the macroscopic and microscopic
      features of the three species were compared. It was found that some microscopic
      characteristics, including transverse shape of mericarp, presence or absence of
      reticulate cells and non-glandular hairs, as well as fluorescence of endocarp,
      were of diagnostic significance. Moreover, essential oils were qualitatively and
      semi-quantitatively analyzed using GC-MS. The analytical results indicated
      significant chemical variations in different species: in FVF, trans-anethole
      (83.20%) was the predominant volatile compound followed by estragole (5.03%) and
      limonene (3.45%), while in AGF, the first, second and third compounds with
      highest content were carvone (42.58%), apiol (20.76%) and limonene (20.32%), and
      in CCF were cuminlaldehyde (36.00%), 2-caren-10-al (23.25%) and gamma-terpinene
      (9.65%), respectively. In conclusion, the proposed light microscopy coupled with
      fluorescence microscopy and/or GC-MS analysis allowed successful distinguishing
      FVF from AGF and CCF.

PMID- 25994837
TI  - Three-dimensional positioning and control of colloidal objects utilizing
      engineered liquid crystalline defect networks.
AB  - Topological defects in liquid crystals not only affect the optical and
      rheological properties of the host, but can also act as scaffolds in which to
      trap nano or micro-sized colloidal objects. The creation of complex defect
      shapes, however, often involves confining the liquid crystals in curved
      geometries or adds complex-shaped colloidal objects, which are unsuitable for
      device applications. Using topologically patterned substrates, here we
      demonstrate the controlled generation of three-dimensional defect lines with non
      trivial shapes and even chirality, in a flat slab of nematic liquid crystal. By
      using the defect lines as templates and the electric response of the liquid
      crystals, colloidal superstructures are constructed, which can be reversibly
      reconfigured at a voltage as low as 1.3 V. Three-dimensional engineering of the
      defect shapes in liquid crystals is potentially useful in the fabrication of self
      healing composites and in stabilizing artificial frustrated phases. 

PMID- 25994838
TI  - Two doses of rivaroxaban versus aspirin for prevention of recurrent venous
      thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.
AB  - Patients with unprovoked venous thromboembolism (VTE) are at high risk for
      recurrence. Although rivaroxaban is effective for extended VTE treatment at a
      dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit
      to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not
      been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a
      multicentre, randomised, double-blind, active-controlled, event-driven study
      comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and
      10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in
      patients who completed 6-12 months of anticoagulant therapy for their index acute
      VTE event. All treatments will be given for 12 months. The primary efficacy
      objective is to determine whether both doses of rivaroxaban are superior to
      aspirin for the prevention of symptomatic recurrent VTE, while the principal
      safety outcome is the incidence of major bleeding. The trial is anticipated to
      enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months.
      In conclusion, the EINSTEIN CHOICE study will provide new insights into the
      optimal antithrombotic strategy for extended VTE treatment by comparing two doses
      of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439). 

PMID- 25994839
TI  - Simulation of the mechanical interlocking capacity of a rough bone implant
      surface during healing.
AB  - BACKGROUND: When an implant is inserted in the bone the healing process starts to
      osseointegrate the implant by creating new bone that interlocks with the implant.
      Biomechanical interlocking capacity is commonly evaluated in in vivo experiments.
      It would be beneficial to find a numerical method to evaluate the interlocking
      capacity of different surface structures with bone. In the present study, the
      theoretical interlocking capacity of three different surfaces after different
      healing times was evaluated by the means of explicit finite element analysis.
      METHODS: The surface topographies of the three surfaces were measured with
      interferometry and were used to construct a 3D bone-implant model. The implant
      was subjected to a displacement until failure of the bone-to-implant interface
      and the maximum force represents the interlocking capacity. RESULTS: The
      simulated ratios (test/control) seem to agree with the in vivo ratios of Halldin
      et al. for longer healing times. However the absolute removal torque values are
      underestimated and do not reach the biomechanical performance found in the study
      by Halldin et al. which might be a result of unknown mechanical properties of the
      interface. CONCLUSION: Finite element analysis is a promising method that might
      be used prior to an in vivo study to compare the load bearing capacity of the
      bone-to-implant interface of two surface topographies at longer healing times.

PMID- 25994841
TI  - Commensurability and finite size effects in lattice simulations of diblock
      copolymers.
AB  - Lattice Monte Carlo (MC) simulations provide an efficient method for exploring
      the structure and phase behavior of block polymer melts. However, the results of
      such simulations may differ from the equilibrium behavior of a hypothetical
      infinite system as a consequence of the finite size of the simulation box.
      Standard finite-size scaling techniques cannot be employed to remove the effects
      of a small system size due to incommensurability between the ordered structure
      domain spacing and the periodicity of the simulation box. This work describes a
      systematic approach to estimating the equilibrium domain spacing in lattice MC
      simulations of symmetric diblock copolymers, and thereby minimize the effects of
      incommensurability. Results for simulations with commensurate simulation boxes,
      which are designed to be commensurate with the preferred lattice periodicity but
      contain different numbers of unit cells, show that once the effects of
      incommensurability are removed, the effects of finite size alone are relatively
      small. 

PMID- 25994840
TI  - InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams.
AB  - BACKGROUND: Set comparisons permeate a large number of data analysis workflows,
      in particular workflows in biological sciences. Venn diagrams are frequently
      employed for such analysis but current tools are limited. RESULTS: We have
      developed InteractiVenn, a more flexible tool for interacting with Venn diagrams
      including up to six sets. It offers a clean interface for Venn diagram
      construction and enables analysis of set unions while preserving the shape of the
      diagram. Set unions are useful to reveal differences and similarities among sets
      and may be guided in our tool by a tree or by a list of set unions. The tool also
      allows obtaining subsets' elements, saving and loading sets for further analyses,
      and exporting the diagram in vector and image formats. InteractiVenn has been
      used to analyze two biological datasets, but it may serve set analysis in a broad
      range of domains. CONCLUSIONS: InteractiVenn allows set unions in Venn diagrams
      to be explored thoroughly, by consequence extending the ability to analyze
      combinations of sets with additional observations, yielded by novel interactions
      between joined sets. InteractiVenn is freely available online at:
      www.interactivenn.net .

PMID- 25994842
TI  - [Inverted takotsubo cardiomyopathy due to subarachnoid haemorrhage].
AB  - We present a case of a 34-year-old woman with cardiogenic shock after successful
      resuscitation. In the medical history migraine was known. Emergency
      echocardiography demonstrated left ventricular dysfunction with hypokinetic basal
      and midventricular segments and hyperkinetic apex. Cerebral computed tomography
      suggested a massive subarachnoid haemorrhage (SAH) with transtentorial
      herniation, so that taking into account the clinical history (severe headache)
      the diagnosis of a SAH-associated inverted takotsubo cardiomyopathy could be
      made. In the case of subarachnoid haemorrhage it should be noted that
      extracerebral organ dysfunction, e.g. inverted takotsubo cardiomyopathy,
      frequently occurs. 

PMID- 25994843
TI  - [Mortality of hematology-oncology patients with neutropenia in intensivecare].
AB  - BACKGROUND: Febrile neutropenia remains one of the most common reasons for
      hospital admission of patients with underlying oncologic disease. These patients
      have an up to 10-fold increased risk of developing sepsis, which often leads to
      these patients being transferred to the intensive care unit (ICU). The survival
      of neutropenic patients with sepsis in particular has improved in recent years,
      due to advanced therapy in intensive care (surviving sepsis campaign); however
      few large international studies of neutropenic cancer patients in the ICU are
      available. METHODS: In a retrospective study, 59 episodes of neutropenic cancer
      patients in the internal medicine ICU at the University Hospital of Cologne over
      a period of 2 years were analyzed. RESULTS: Pneumonia with or without sepsis are
      the main admission diagnoses of neutropenic cancer patients in the ICU. The
      mortality rate of these patients is very high (50.8 %). Pneumonia and sepsis,
      stem cell transplantation, mechanical ventilation, and acute renal failure with
      or without dialysis are correlated with mortality. CONCLUSION: Cancer patients
      should be admitted immediately to the ICU if they have signs of sepsis for early
      monitoring and treatment. Neutropenic patients have an increased risk for
      infectious complications and a risk for sepsis with higher mortality rates.

PMID- 25994844
TI  - Emergence of fusarioses in a university hospital in Turkey during a 20-year
      period.
AB  - Fusarium species have started appearing increasingly as the main cause of
      infections, particularly in immunocompromised patients. In this study, we aimed
      to present the first epidemiological data from Turkey, analyze fusariosis cases
      that have been monitored in a university hospital during the past 20 years,
      identify the responsible Fusarium species, and determine antifungal
      susceptibilities. A total of 47 cases of fusariosis was included in the study.
      Fusarium isolates were identified by multilocus sequence typing (MLST).
      Antifungal susceptibility was tested by the broth microdilution method according
      to the Clinical and Laboratory Standards Institute (CLSI) methodology. Of the
      Fusarium infections, 23.4 % were superficial, 44.7 % were locally invasive, and
      31.9 % were disseminated. A significant increase was observed over the years. The
      Fusarium fujikuroi species complex (FFSC) proved to be the most frequent agent
      group (17 cases; 51.5 %), followed by the Fusarium solani species complex (FSSC)
      (14 cases; 42.4 %), the Fusarium dimerum species complex (FDSC), and the Fusarium
      oxysporum species complexes (FOSC) (one case each). Amphotericin B had the
      highest in vitro activity against all species. Voriconazole and posaconazole
      showed interspecies variability across and within Fusarium species complexes. In
      conclusion, our data support the fact that regional differences exist in the
      distribution of the Fusarium species and that species-specific differences are
      observed in antifungal susceptibility patterns. The monitoring of local
      epidemiological data by determining fungal identity and susceptibility are of
      importance in guiding the clinical follow-up of patients. 

PMID- 25994845
TI  - Prevalence and risk factors of sialocele formation after partial superficial
      parotidectomy: A multi-institutional analysis of 357 consecutive patients.
AB  - BACKGROUND: The purpose of this study was to identify the prevalence of
      sialoceles and the risk factors associated with their formation after
      parotidectomy. METHODS: We performed a retrospective analysis of the data from
      consecutive patients who underwent partial superficial parotidectomy of parotid
      tumors. Demographic data, preoperative imaging results, operative variables,
      including tumor type, incision type, tumor size, and method of parenchymal
      disruption were assessed. RESULTS: Twenty-three of 357 patients (6.4%) undergoing
      partial superficial parotidectomy developed sialoceles during the postoperative
      period. Sialoceles occurred more often in patients who had tumors in the anterior
      portion of the parotid gland. Multivariate analysis showed that an anterior tumor
      location was a significant risk factor for sialocele formation. CONCLUSION: The
      incidence of sialocele development was 6.4% in patients undergoing partial
      superficial parotidectomy. An anterior tumor location may increase the risk of
      sialocele formation. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E941-E944,
      2016.

PMID- 25994846
TI  - A universal radiation protection system based on individual standardised
      integrated doses.
AB  - A 'Universal Radiation Protection System' (URPS) is proposed in this paper with a
      novel philosophy, concept and methodology. It applies a 'Standardised Integrated
      Dose System' (SIDS) based on health risk limits for workers and public, no matter
      where they live in the world. The URPS assigns equal radiation health risk limit
      to an individual by integrating doses from national natural background (NBG)
      radiation and from man-made sources. For public, the SIDS integrates doses from
      planned exposure situations within a dose limit (e.g. 1 mSv y(-1)) on top of the
      mean national NBG dose in a country. For workers, the SIDS integrates within a
      dose limit (e.g. 20 mSv y(-1)) of occupational dose and doses from mean national
      NBG and from planned exposure situations as a member of public within the public
      dose limit. A panorama overview and the rationale in support of the URPS are
      presented and discussed with a hope to ignite further thoughts and ideas towards
      establishing the URPS for universal use. 

PMID- 25994847
TI  - Variability of [18F]FDG administered activities among patients undergoing PET
      examinations: an international multicenter survey.
AB  - Given the large number of [(18)F]fluorodeoxyglucose (FDG) PET examinations
      performed annually throughout the world, reduction of the administered activity
      without compromise of the clinical information being sought is encouraged.
      Guidelines issued by the SNMMI and European Association of Nuclear Medicine
      (EANM) differ greatly on the choice of the activity that should be administered
      to patients: the EANM suggests a personalised activity based on the patient's
      body weight, whereas the SNMMI recommends the administration of fixed activities.
      The authors analysed a database of 24 716 [(18)F]FDG administrations performed
      worldwide in 15 PET centres to assess the degree of heterogeneity, in relation to
      available technology, operational protocols and reference guidelines. Median
      activities based on the patients' body weight were 43 % lower than fixed-activity
      administrations (p < 0.001). When TOF scanners are available, the median activity
      is lowered, but when comparing centres with the same technology or those that use
      the same operational protocols, weight-based activities are still significantly
      lower than fixed activities. 

PMID- 25994848
TI  - A practical method for skin dose estimation in interventional cardiology based on
      fluorographic DICOM information.
AB  - A practical method for skin dose estimation for interventional cardiology
      patients has been developed to inform pre-procedure planning and post-procedure
      patient management. Absorbed dose to the patient skin for certain interventional
      radiology procedures can exceed thresholds for deterministic skin injury,
      requiring documentation within the patient notes and appropriate patient follow
      up. The primary objective was to reduce uncertainty associated with current
      methods, particularly surrounding field overlap. This was achieved by considering
      rectangular field geometry incident on a spherical patient model in a polar
      coordinate system. The angular size of each field was quantified at surface of
      the sphere, i.e. the skin surface. Computer-assisted design software enabled the
      modelling of a sufficient dataset that was subsequently validated with
      radiochromic film. Modelled overlap was found to agree with overlap measured
      using film to within 2.2 degrees  +/- 2.0 degrees , showing that the overall
      error associated with the model was < 1 %. Mathematical comparison against
      exposure data extracted from procedural Digital Imaging and Communication in
      Medicine files was used to generate a graphical skin dose map, demonstrating the
      dose distribution over a sphere centred at the interventional reference point.
      Dosimetric accuracy of the software was measured as between 3.5 and 17 % for
      different variables.

PMID- 25994849
TI  - Effect of Ti:sapphire laser on shear bond strength of orthodontic brackets to
      ceramic surfaces.
AB  - BACKGROUND AND OBJECTIVES: With increasing demand for orthodontic treatments in
      adults, orthodontists continue to debate the optimal way to prepare ceramic
      surfaces for bonding. This study evaluated the effects of a Ti:sapphire laser on
      the shear bond strength (SBS) of orthodontic brackets bonded to two ceramic
      surfaces (feldspathic and IPS Empress e-Max) and the results were compared with
      those using two other lasers (Er:YAG and Nd:YAG) and 'conventional' techniques,
      i.e., sandblasting (50 um) and hydrofluoric (HF) acid. MATERIALS AND METHODS: In
      total, 150 ceramic discs were prepared and divided into two groups. In each
      group, the following five subgroups were prepared: Ti:sapphire laser, Nd:YAG
      laser, Er:YAG laser, sandblasting, and HF acid. Mandibular incisor brackets were
      bonded using a light-cured adhesive. The samples were stored in distilled water
      for 24 hours at 37 degrees C and then thermocycled. Extra samples were prepared
      and examined using scanning electron microscopy (SEM). SBS testing was performed
      and failure modes were classified. ANOVA and Tukey's HSD tests were used to
      compare SBS among the five subgroups (P < 0.05). RESULTS: Feldspathic and IPS
      Empress e-Max ceramics had similar SBS values. The Ti:sapphire femtosecond laser
      (16.76 +/- 1.37 MPa) produced the highest mean bond strength, followed by
      sandblasting (12.79 +/- 1.42 MPa) and HF acid (11.28 +/- 1.26 MPa). The Er:YAG
      (5.43 +/- 1.21 MPa) and Nd:YAG laser (5.36 +/- 1.04 MPa) groups were similar and
      had the lowest SBS values. More homogeneous and regular surfaces were observed in
      the ablation pattern with the Ti:sapphire laser than with the other treatments by
      SEM analysis. CONCLUSIONS: Within the limitations of this in vitro study,
      Ti:sapphire laser- treated surfaces had the highest SBS values. Therefore, this
      technique may be useful for the pretreatment of ceramic surfaces as an
      alternative to 'conventional' techniques.

PMID- 25994850
TI  - Changes in Spirometry After Left Ventricular Assist Device Implantation.
AB  - Left ventricular assist devices (LVADs) are increasingly being used as life
      saving therapy in patients with end-stage heart failure. The changes in
      spirometry following LVAD implantation and subsequent unloading of the left
      ventricle and pulmonary circulation are unknown. In this study, we explored long
      term changes in spirometry after LVAD placement. In this retrospective study, we
      compared baseline preoperative pulmonary function test (PFT) results to post-LVAD
      spirometric measurements. Our results indicated that pulmonary function tests
      were significantly reduced after LVAD placement (forced expiratory volume in one
      second [FEV1 ]: 1.9 vs.1.7, P = 0.016; forced vital capacity [FVC]: 2.61 vs.
      2.38, P = 0.03; diffusing capacity of the lungs for carbon monoxide [DLCO]: 14.75
      vs. 11.01, P = 0.01). Subgroup analysis revealed greater impairment in lung
      function in patients receiving HeartMate II (Thoratec, Pleasanton, CA, USA) LVADs
      compared with those receiving HeartWare (HeartWare, Framingham, MA, USA) devices.
      These unexpected findings may result from restriction of left anterior hemi
      diaphragm; however, further prospective studies to validate our findings are
      warranted.

PMID- 25994851
TI  - Bullying in childhood may be linked to heart disease risk, study says.

PMID- 25994852
TI  - Youngiasides A and C Isolated from Youngia denticulatum Inhibit UVB-Induced MMP
      Expression and Promote Type I Procollagen Production via Repression of MAPK/AP
      1/NF-kappaB and Activation of AMPK/Nrf2 in HaCaT Cells and Human Dermal
      Fibroblasts.
AB  - This study investigated the effects of youngiaside A (YA), youngiaside C (YC),
      and Youngia denticulatum extract (YDE) on extrinsic aging and assessed its
      molecular mechanisms in UVB-irradiated HaCaT keratinocytes and human dermal
      fibroblasts (HDFs). The results showed that YA, YC, and YDE decreased matrix
      metalloproteinase (MMP) expression and production in HaCaT cell and HDFs and
      increased collagen expression and production in HDFs. In addition, YA, YC, and
      YDE significantly increased antioxidant enzyme expression, thereby down
      regulating UVB-induced reactive oxygen species (ROS) production and ROS-induced
      mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) signaling
      in HaCaT cells. Furthermore, YA, YC, and YDE reduced phosphorylation of
      IkappaBalpha and IKKalpha/beta, blocked nuclear factor-kappaB (NF-kappaB) p65
      nuclear translocation, and strongly suppressed pro-inflammatory mediators.
      Finally, YA, YC, and YDE augmented UVB-induced adenosine monophosphate activated
      protein kinase (AMPK) phosphorylation and YA and YC did not inhibit MMP-1
      production in AMPK inhibitor or nuclear factor-erythroid 2-related factor-2
      (Nrf2) siRNA-treated HaCaT cells. The results suggest that these compounds could
      be potential therapeutic agents for prevention and treatment of skin photoaging. 

PMID- 25994853
TI  - Comparison of the pharmacokinetics of erlotinib administered in complete fasting
      and 2 h after a meal in patients with lung cancer.
AB  - BACKGROUND: The recommended dose of erlotinib is 150 mg daily either 1 h before a
      meal (complete fasting) or 2 h after a meal (2 h post-meal), because of the food
      effect. METHODS: We conducted a cross-over pharmacokinetic study to compare the
      fed bioequivalence in the two conditions. RESULTS: Twenty-three patients with non
      small cell lung cancer were included in the analysis. AUC0-24 and C max in the 2
      h post-meal status were significantly higher than in the complete fasting status
      (GMR = 1.33, P < 0.001; GMR = 1.44, P < 0.001, respectively). However, because
      the concentration of erlotinib did not reach the steady state within 7 days in
      the complete fasting state, we conducted analyses only on day 14, which showed no
      significant difference in AUC0-24 or C max between the two conditions. The more
      rapid increase in AUC0-24 and C min did not produce any earlier and more severe
      toxic events. CONCLUSION: The AUC0-24 increased significantly faster (48-53 %
      greater) in the 2-h post-meal status than in complete fasting status, which
      suggested that the two gastric emptying states might differ in their absorption.
      However, there was no clinically significant difference in bioavailability or
      toxicity between the two clinically used fed conditions at least in 14 days.

PMID- 25994854
TI  - Safety, tolerability, and efficacy of oxaliplatin-based adjuvant chemotherapy
      after curative resection of hepatic or extrahepatic metastases of Stage IV
      colorectal cancer.
AB  - PURPOSE: Surgery is the only potentially curative strategy for patients who have
      Stage IV colorectal cancer (CRC) with resectable metastases, but relapse is
      common. Randomized trials of adjuvant 5-FU-based systemic chemotherapy have not
      demonstrated any benefit after resection of liver metastases. We evaluated the
      efficacy, safety, and tolerability of oxaliplatin-based adjuvant chemotherapy
      after curative resection of hepatic or extrahepatic metastases of CRC. METHODS:
      We retrospectively studied data for 88 consecutive patients with Stage IV CRC who
      underwent curative resection of metastases followed by oxaliplatin-based adjuvant
      chemotherapy between March 2007 and June 2013. RESULTS: The 3-year relapse-free
      survival (RFS) rate was 54.0 %. There was no significant difference in 3-year RFS
      between patients with metastases confined to the liver (52.7 %) and patients with
      extrahepatic metastases (57.2 %). Multivariate analysis revealed that the site of
      the primary tumor (right-sided colon or left-sided colon/rectum) and the number
      of metastases (solitary or multiple) were predictors of RFS. Scheduled courses
      were completed in 80.7 % of the patients. Except for neutropenia (47.7 %), severe
      adverse events were observed in <5 % of patients. CONCLUSIONS: Oxaliplatin-based
      adjuvant chemotherapy could be an effective option for selected patients with
      Stage IV CRC after curative resection of hepatic or extrahepatic metastases, and
      is both safe and tolerable.

PMID- 25994855
TI  - Outcome predictors of empirical slow pathway modulation: clinical and procedural
      characteristics and long-term follow-up.
AB  - OBJECTIVE: Catheter-based modulation of the slow pathway is the first-line
      therapy of atrioventricular nodal reentrant tachycardia (AVNRT), the most common
      supraventricular tachycardia (SVT). In patients with a typical history, in whom
      AVNRT is not inducible during an electrophysiological study, the current
      guidelines allow consideration of empirical slow pathway modulation (ESPM) under
      the precondition that both, dual nodal pathway physiology (DNPP) and an ECG
      documentation compatible with AVNRT exist. This recommendation is based on small
      series. Furthermore, it is unknown whether ESPM is beneficial in the presence of
      ECG documentation but the absence of DNPP or vice versa in the presence of DNPP
      but absence of ECG documentation. METHODS: Out of 3003 patients who underwent
      slow pathway modulation from 1993 to 2013, we included 116 patients (68 female;
      median age 47.0 years) with symptomatic tachycardia who had non-inducible SVT.
      All patients either had ECG documentation of SVT (66 %) or DNPP (89 %) or both
      (54 %). All patients underwent ESPM. No severe complications occurred. RESULTS:
      After a follow-up time of 64 +/- 5.3 months, 81 % of all patients had benefited
      from ESPM (49 % freedom of symptoms, 32 % improvement). In patients with ECG
      documentation but absence of DNPP 100 % benefited (85 % freedom of symptoms; 15 %
      improvement). In patients with DNPP but absence of ECG documentation 75 %
      benefited (40 % freedom of symptoms, 35 % improvement). CONCLUSION: In a large
      cohort of patients, ESPM is a safe procedure that improves clinical symptoms in
      the majority of patients during long-term follow-up. We show for the first time
      that this also applies for cases where there is no DNPP but a characteristic ECG
      documentation, and vice versa.

PMID- 25994856
TI  - Linking community resources in diabetes care: a role for technology?
AB  - Designing and implementing effective lifestyle modification strategies remains
      one of the great challenges in diabetes care. Historically, programs have focused
      on individual behavior change with little or no attempt to integrate change
      within the broader social framework or community context. However, these
      contextual factors have been shown to be associated with poor diabetes outcomes,
      particularly in low-income minority populations. Recent evidence suggests that
      one way to address these disparities is to match patient needs to existing
      community resources. Not only does this position patients to more quickly adapt
      behavior in a practical way, but this also refers patients back to their local
      communities where a support mechanism is in place to sustain healthy behavior.
      Technology offers a new and promising platform for connecting patients to
      meaningful resources (also referred to as "assets"). This paper summarizes
      several noteworthy innovations that use technology as a practical bridge between
      healthcare and community-based resources that promote diabetes self-care. 

PMID- 25994857
TI  - Pro-aromatic and anti-aromatic pi-conjugated molecules: an irresistible wish to
      be diradicals.
AB  - Aromaticity is an important concept to understand the stability and physical
      properties of pi-conjugated molecules. Recent studies on pro-aromatic and anti
      aromatic molecules revealed their irresistible tendency to become diradicals in
      the ground state. Diradical character thus becomes another very important concept
      and it is fundamentally correlated to the physical (optical, electronic and
      magnetic) properties and chemical reactivity of most of the organic
      optoelectronic materials. Molecules with distinctive diradical character show
      unique properties which are very different from those of traditional closed-shell
      pi-conjugated systems, and thus they have many potential applications in organic
      electronics, spintronics, non-linear optics and energy storage. This critical
      review first introduces the fundamental electronic structure of Kekule diradicals
      within the concepts of anti-aromaticity and pro-aromaticity in the context of
      Huckel aromaticity and diradical character. Then recent research studies on
      various stable/persistent diradicaloids based on pro-aromatic and anti-aromatic
      compounds are summarized and discussed with regard to their synthetic chemistry,
      physical properties, structure-property relationships and potential material
      applications. A summary and personal perspective is given at the end. 

PMID- 25994858
TI  - Birth prevalence of Robin sequence in the Netherlands from 2000-2010: a
      retrospective population-based study in a large Dutch cohort and review of the
      literature.
AB  - The birth prevalence of Robin sequence (RS) is frequently cited to be 1 in 8,500
      to 14,000 live births (range: 7,1-11,8 per 100.000), which is based on just a few
      epidemiological studies. The objective of this study is to contribute to the
      limited knowledge of the epidemiology of RS by determining the frequency of RS in
      a cleft palate (CP) population and the estimated birth prevalence in live births
      in the Netherlands, using distinct diagnostic criteria. A retrospective
      population-based analysis of the National Cleft Registry was performed in order
      to obtain all CP patients registered in the Netherlands from 2000-2010, in
      addition to a thorough review of the medical records in three Dutch Academic
      Pediatric Hospitals for the same period. Furthermore, a systematic search of the
      literature was conducted to allow for comparison of our findings. The Dutch birth
      prevalence of RS was estimated to be 1:5,600 live births (or 17.7 per 100,000),
      with a slight female predominance. RS was estimated to occur in a third of the CP
      population and patients with RS had a more severe cleft grade than the general CP
      population. The literature search yielded 42 studies reporting the birth
      prevalence for RS, which varied between 1:3,900 and 1:122,400 (0.8-32.0 per
      100,000), with a mean prevalence of 1:24,500 (8.0 per 100,000). The birth
      prevalence of RS in the Netherlands was higher than reported for most other
      countries when similar diagnostic criteria were used, with a slight female
      predominance. A third of the general CP could be classified as RS.

PMID- 25994859
TI  - Eriodictyol Attenuates beta-Amyloid 25-35 Peptide-Induced Oxidative Cell Death in
      Primary Cultured Neurons by Activation of Nrf2.
AB  - Oxidative stress plays an important role in the pathogenesis of neurodegenerative
      diseases, including Alzheimer's disease (AD). Eriodictyol, a flavonoid isolated
      from the Chinese herb Dracocephalum rupestre, has long been established as an
      antioxidant. The present study was designed to investigate the effect of
      eriodictyol on beta-amyloid 25-35 peptide (Abeta25-35)-induced oxidative cell
      death in primary neurons and to explore the role of the nuclear factor erythroid
      2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in this
      process. For this purpose, primary cultures of cortical neurons were exposed to
      15 MUM Abeta25-35 in the absence or presence of eriodictyol (20, 40 and 80 MUM).
      The results revealed that Abeta25-35-induced cytotoxicity and apoptotic
      characteristics such as activation of JNK/p38 apoptotic signaling pathway were
      effectively attenuated by eriodictyol pretreatment. Eriodictyol treatment also
      resulted in an increase in Nrf2 protein levels and subsequent activation of ARE
      pathway genes in primary cultured neurons. The protective effects of eriodictyol
      were attenuated by RNA interference-mediated knockdown of Nrf2 expression. Taken
      together, these results clearly demonstrate that eriodictyol protects neurons
      against Abeta25-35-induced cell death partially through Nrf2/ARE signaling
      pathway, which further supports that eriodictyol might be a promising novel
      therapeutic agent for AD. 

PMID- 25994860
TI  - The impact of the new proposed Papanicolaou Society of Cytopathology terminology
      for pancreaticobiliary cytology in endoscopic US-FNA: A single-institutional
      experience.
AB  - BACKGROUND: The Papanicolaou Society of Cytopathology has recently published a
      new proposal for pancreaticobiliary cytology terminology. For the current study,
      the authors applied this new classification for pancreaticobiliary cytology to a
      set of previously diagnosed endoscopic ultrasound (EUS)-guided fine-needle
      aspiration (EUS-FNA) samples and correlated the results with those from the
      corresponding available final surgical specimens. METHODS: Pancreatic FNA
      specimens were retrospectively collected from a 12-month period at the Mayo
      Clinic in Jacksonville, Florida. Cases with cytohistologic disagreement were
      reviewed to assess the reasons for discrepancies. The sensitivity and specificity
      of EUS-FNA specimens were assessed using the Pearson chi-square test. RESULTS:
      One hundred fifty-five pancreatic FNA specimens were retrieved. The median
      patient age was 70 years (range, 25-93 years). Eleven specimens previously
      classified as negative and 3 previously classified as non-diagnostic were
      reclassified as neoplastic:other, as well as all specimens primarily classified
      as atypical or positive for neoplasm and half the specimens primarily classified
      as suspicious. All positive specimens remained within their same categories in
      the revised classification. Sixteen patients (10.3%) had surgical resection
      specimens available, and complete or partial agreement with FNA results was
      achieved in 13 of those surgical specimens (81.2%). Reasons for discrepancy
      comprised sampling errors in 5 specimens and an interpretation error in 1
      specimen. Overall, sensitivity was 66.7%, specificity was 66.7%, the positive
      predictive value was 88.9%, and the negative predictive value was 33.3%.
      CONCLUSIONS: The application of the new proposed terminology for
      pancreaticobiliary cytology had a greater impact among specimens that were
      previously classified as atypical and suspicious. EUS-FNA of the pancreas is a
      highly accurate method, and its use, allied with the new proposed terminology,
      may ultimately contribute to better outcomes.

PMID- 25994861
TI  - Cruzipain: An Update on its Potential as Chemotherapy Target against the Human
      Pathogen Trypanosoma cruzi.
AB  - Chagas' disease is one of the most impactful and prevalent neglected tropical
      diseases in the Americas, specially affecting the poor and underdeveloped areas
      in Latin America. Aggravating this scenario, the medicines used in the current
      chemotherapy are old, toxic and present a low efficacy to treat the chronic stage
      of this disease. In addition, resistant strains of Trypanosoma cruzi, the
      etiological agent, are frequently reported. So, there is an imperative
      requirement for novel chemotherapeutic options to treat this debilitating
      disease. In this context, peptidases have emerged as potential targets and,
      consequently, proteolytic inhibitors have confirmed to be valuable drugs against
      several human pathologies. In this line of thinking, T. cruzi produces a major
      multifunctional cysteine peptidase, named cruzipain, which directly and/or
      indirectly orchestrates several physiological and pathological processes, which
      culminate in a successful parasitic infection. Taken together, these findings
      point out that cruzipain is one of the most important targets for driving a
      chemotherapy approach against the human pathogen T. cruzi. The present review
      summarizes some of the recent advances and failures in this area, with particular
      emphasis on recently published studies. 

PMID- 25994862
TI  - Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids
      in Higher Fungi.
AB  - Cyathane diterpenoids, occurring exclusively in higher basidiomycete (mushrooms),
      represent a structurally diverse class of natural products based on a
      characteristic 5-6-7 tricyclic carbon scaffold, including 105 members reported to
      date. These compounds show a diverse range of biological activities, such as
      antimicrobial, anti-MRSA, agonistic toward the kappa-opioid receptor,
      antiinflammatory, anti-proliferative and nerve growth factor (NGF)-like
      properties. The present review focuses on the structure diversity, structure
      elucidation and biological studies of these compounds, including mechanisms of
      actions and structure-activity relationships (SARs). In addition, new progress in
      chemical synthesis of cyathane diterpenoids is discussed. 

PMID- 25994863
TI  - HER2-mediated anticancer drug delivery: strategies to prepare targeting ligands
      highly specific for the receptor.
AB  - HER2 receptor, for its involvement in tumorigenesis, has been largely studied as
      topic in cancer research. In particular, the employment of trastuzumab
      (Herceptin), a humanized anti-HER2 antibody, showed several clinical benefits in
      the therapy against the breast cancer. Moreover, for its accessible extracellular
      domain, this receptor is considered an ideal target to deliver anticancer drugs
      for the receptormediated anticancer therapy. By now, monoclonal antibody and its
      fragments, affibody, and some peptides have been employed as targeting agents in
      order to deliver various drugs to HER2 positive tumor cells. In particular, the
      ability to perform a fast and reliable screening of a large number of peptide
      molecules would make possible the selection of highly specific compounds to the
      receptor target. In this regard, the availability of preparing a simplified
      synthetic model which is a good mimetic of the receptor target and can be used in
      a reliable screening method of ligands would be of a strategic importance for the
      development of selective HER2-targeting peptide molecules. Herein, we illustrate
      the importance of HER2-targeted anticancer therapies. We also report on a
      synthetic and effective mimetic of the receptor, which revealed to be a useful
      tool for the selection of specific HER2 ligands. 

PMID- 25994864
TI  - GWA meta-analysis of personality in Korean cohorts.
AB  - Personality is a determinant of behavior and lifestyle that is associated with
      health and human diseases. Despite the heritability of personality traits is well
      established, the understanding of the genetic contribution to personality trait
      variation is extremely limited. To identify genetic variants associated with each
      of the five dimensions of personality, we performed a genome-wide association
      (GWA) meta-analysis of three cohorts, followed by comparison of a family cohort.
      Personality traits were measured with the Revised NEO Personality Inventory for
      the five-factor model (FFM) of personality. We investigated the top five single
      nucleotide polymorphisms (SNPs) for each trait, and revealed the most highly
      association with neuroticism and TACC2 (rs1010657, P=8.79 * 10(-7)), extraversion
      and PTPN12 (rs12537271, P=1.47 * 10(-7)), openness and IMPAD1 (rs16921695, P=5 *
      10(-8)), agreeableness and RPS29 (rs8015351, P=1.27 * 10(-6)) and
      conscientiousness and LMO4 (rs912765, P=2.91 * 10(-6)). It had no SNP reached the
      GWA study threshold (P<5 * 10(-8)). When expanded the SNPs up to top 100, the
      correlation of PTPRD (rs1029089) and agreeableness was confirmed in Healthy Twin
      cohort with other 13 SNPs. This GWA meta-analysis on FFM personality traits is
      meaningful as it was the first on a non-Caucasian population targeted to FFM of
      personality traits. 

PMID- 25994865
TI  - Brachydactyly Type C patient with compound heterozygosity for p.Gly319Val and
      p.Ile358Thr variants in the GDF5 proregion: benign variants or mutations?
AB  - We report on a Brachydactyly Type C (BDC) patient with clinically inconspicuous
      parents. Molecular genetic analyses revealed compound heterozygosity for two GDF5
      variants. The variant c.956G>T (p.Gly319Val) was inherited from her mother and
      has been reported in exome sequencing projects, whereas c.1073T>C (p.Ile358Thr)
      has never been reported so far. In silico, both variants were predicted to be
      'disease-causing', but the fact that p.Ile358Thr was predicted by SIFT to be
      'tolerated' raised our suspicion. Therefore, we performed in vitro assays. To our
      surprise, GDF5(G319V) showed pronounced loss of function in luciferase reporter
      assays and in vitro chondrogenesis, whereas GDF5(I358T) and GDF5(WT) had
      comparable biological activities. Western blot analyses revealed decreased
      protein levels after overexpression of GDF5(G319V). In absence of linkage or de
      novo mutation, several scenarios could explain the underlying mechanism of the
      patient's phenotype. Owing to reduced activity of GDF5(G319V) in our functional
      assays, p.Gly319Val might be causative for BDC, but typically evoke an
      unrecognizably mild phenotype or even nonpenetrance. Another possibility is that
      our assays failed to pinpoint the disease-causing mechanism of the p.Ile358Thr
      allele. A final possibility is that compound heterozygosity for p.Ile358Thr and
      p.Gly319Val is more deleterious to GDF5 activity than either variant alone. Until
      all possible explanations can be rigorously tested experimentally, a precise
      recurrence risk counseling for the parents and the affected child is not
      possible. 

PMID- 25994866
TI  - Clinical outcomes and the mutation spectrum of the  OTC gene in patients with
      ornithine transcarbamylase  deficiency.
AB  - Ornithine transcarbamylase (OTC) deficiency is an X-linked inborn error of the
      urea cycle that leads to the accumulation of ammonia, resulting in neurological
      deficits. This study was performed to describe the clinical outcomes, biochemical
      features and molecular spectra of patients with OTC deficiency. A total of 49
      patients from 47 unrelated Korean pedigrees were included who were diagnosed with
      OTC deficiency based on biochemical findings and molecular analyses. Patient
      clinical features,biochemical findings and molecular data were analyzed
      retrospectively. Males with neonatal-onset phenotype presented with seizure or
      altered mentality (n=20). Biochemical findings showed high blood ammonia
      (1132.5+/-851.6 MUmol l (- 1)) and urineorotic acid (1840.7+/-1731.3 mmol mol(-
      1) Cr) levels. There were also five males with late-onset disease who presented
      with vomiting, irritability and seizure at age 8.2+/-9.4 years old (range, 0.6-20
      years). Symptomatic females presented with vomiting,seizure, and altered
      mentality at age 3.5+/-3.5 years (range, 0.2-12.8 years; n=24). More males with
      the late-onset form and symptomatic females displayed mild hyperammonemia and
      orotic aciduria compared with those showing a neonatal phenotype (P<0.05).
      Molecular analysis identified 37 different mutations (22 missense, 5 large
      deletions, 4 small deletions, 1 insertion,3 nonsense and 2 splice sites) from all
      49 patients; the mutations were dispersed throughout all coding exons. In Korean
      patients with OTC deficiency, mutations in OTC are genetically heterogeneous.
      Male patients with the neonatal-onset phenotype showed poor outcomes because of
      severe hyperammonemia. Early diagnosis and interventions for hyperammonemia can
      provide more favorable prognosis.

PMID- 25994867
TI  - mtDNA diversity of the Zapotec in Mexico suggests  a population decline long
      before the first contact  with Europeans.
AB  - The New World is the last continent colonized by anatomically modern humans, Homo
      sapiens. The first migrants entered the New World from Asia through Beringia. It
      is suggested that there were three streams of Asian gene flow, one major and two
      additional minor gene flows. The first major migrants took a Pacific coastal
      route and began spreading to the American continent before the opening of the ice
      free corridor. We investigated the diversity of full-length mitochondrial DNA
      genomes of the Zapotec population, residing in the Mesoamerican region, and
      reconstructed their demographic history using Bayesian Skyline Plots. We
      estimated the initial date of gene flow into the New World by Zapotec ancestors
      at around 17 000-19 000 years ago,which is highly concordant with previous
      studies. We also show a population decline after the initial expansion. This
      decline started 4000 years ago, long before European contact with Native
      Americans. This indicates that other factors including climatec hange should be
      considered to explain the observed demographic pattern.

PMID- 25994869
TI  - Genetic association of key Th1/Th2 pathway candidate genes, IRF2, IL6, IFNGR2,
      STAT4 and IL4RA, with atopic asthma in the Indian population.
AB  - Asthma is a complex, multifactorial disease resulting due to dysregulated immune
      responses. Genetic factors contribute significantly to asthma pathogenesis, and
      identification of these factors is one of the major goals in understanding the
      disease. Th1/Th2 helper differentiation has a critical role in modulating the
      phenotypes associated with atopic asthma. This study was aimed at identifying
      genetic modifiers of asthma in selected genes involved in T helper
      differentiation. A total of 354 single-nucleotide polymorphisms (SNPs) in 33
      candidate genes were genotyped in a case-control cohort (cases=147, controls=199)
      and families (n=247) using Illumina's Golden Gate Assay. Five SNPs, rs3733475A/C
      (IRF2), rs2069832A/G (IL6), rs2012075G/A (IFNGR2) and rs1400656G/A (STAT4) and
      rs1805011C/A (IL4RA) were found to be associated with asthma in family based as
      well as in case-control analyses (P=0.002, P=0.001, P=0.004, P=0.003 and P=0.001,
      respectively). Interestingly, the minor alleles at these loci showed a protective
      effect. A five loci haplotype, TAACG, in IRF2 gene, was significantly associated
      with asthma in families (P=1.1 * 10(-6)) and in case-control cohort (P=0.01). In
      conclusion, our studies led to identification of some key candidate genes, namely
      IRF2, IL6, IFNGR2, STAT4 and IL4RA that modulate genetic susceptibility to asthma
      in the Indian population. Also, this is the first report of independent
      association of IL6 gene polymorphism with atopic asthma. 

PMID- 25994868
TI  - Genetics of atrial fibrillation: from families to genomes.
AB  - Atrial fibrillation (AF) is the most common cardiac rhythm disorder and the
      prevalence is increasing. The disease confers an increased risk of severe
      complications such as heart failure, stroke and death, yet the treatment options
      available are insufficient. AF can develop secondary to other diseases, but there
      is also evidence of a heritable component. The molecular basis for the
      heritability of AF has been explored in depth over the past decade. Rare variants
      have been identified in ion channels, transcription factors and a wide range of
      other genes. More recently, common variant analyses have identified 14 genetic
      loci associated with AF. Thus, the genetics of AF is complex and heterogeneous.
      In this review, we describe the common and rare variants identified for AF, the
      potential clinical implications of these variants and the future directions in
      this field. Increasing our understanding of the pathophysiology of AF will aid
      the development of new and improved treatment strategies and risk prediction of
      AF, the first steps toward a more individualized treatment of the arrhythmia. 

PMID- 25994870
TI  - Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse
      reactions (SCARs) in Thai epilepsy children.
AB  - CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism.
      CYP2C9*3 is a loss of function polymorphism. This study was designed to
      investigate genetic association between CYP2C9*3 and aromatic AED-induced severe
      cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced
      SCARs patients (20 phenobarbital and 17 phenytoin) and 35 tolerances (19
      phenobarbital and 16 phenytoin) were enrolled. CYP2C9*3 was genotyped by allele
      specific PCRs. The association between CYP2C9*3 with phenytoin-induced SCARs and
      phenobarbital-induced SCARs were analyzed in comparison with tolerances and
      healthy samples. Significant association between phenytoin-induced SCARs and
      CYP2C9*3 was discovered (odds ratio=14.52; 95% confidence interval (CI)=1.18
      infinity, P-value=0.044). CYP2C9*3 was not associated with phenobarbital-induced
      SCARs. This study is the first report of CYP2C9*3 association to phenytoin
      induced SCARs in Thai epileptic children. The CYP2C9*3 is a reasonable predictive
      genetic marker to anticipate SCARs from phenytoin. 

PMID- 25994872
TI  - A commentary on short-term efficacy of N-carbamylglutamate in a patient with N
      acetylglutamate synthase deficiency.

PMID- 25994873
TI  - [60 years hemo- and peritoneal dialysis, 50 years kidney transplantation, 25
      years immunoapheresis in Austria].

PMID- 25994871
TI  - Genome-wide signatures of male-mediated migration  shaping the Indian gene pool.
AB  - Multiple questions relating to contributions of cultural and demographical
      factors in the process of human geographical dispersal remain largely unanswered.
      India, a land of early human settlement and the resulting diversity is a good
      place to look for some of the answers. In this study, we explored the genetic
      structure of India using a diverse panel of 78 males genotyped using the
      GenoChip. Their genome-wide single-nucleotide polymorphism (SNP) diversity was
      examined in the context of various covariates that influence Indian gene pool.
      Admixture analysis of genome-wide SNP data showed high proportion of the
      Southwest Asian component in all of the Indian samples. Hierarchical clustering
      based on admixture proportions revealed seven distinct clusters correlating to
      geographical and linguistic affiliations. Convex hull overlay of Y-chromosomal
      haplogroups on the genome-wide SNP principal component analysis brought out
      distinct non-overlapping polygons of F*-M89, H*-M69, L1-M27, O2a-M95 and O3a3c1
      M117, suggesting a male-mediated migration and expansion of the Indian gene pool.
      Lack of similar correlation with mitochondrial DNA clades indicated a shared
      genetic ancestry of females. We suggest that ancient male-mediated migratory
      events and settlement in various regional niches led to the present day scenario
      and peopling of India.

PMID- 25994874
TI  - Lightweight application for generating clinical research information systems:
      MAGIC.
AB  - BACKGROUND: Our purpose was to build and test a lightweight solution for
      generating clinical research information systems (CRIS) that would allow non-IT
      professionals with basic knowledge of computer usage to quickly define and build
      a ready-to-use, safe and secure web-based clinical research system for data
      management. We use the acronym MAGIC (Medical Application Generator InteraCtive)
      for the system. METHODS: The generated CRIS should be very easy to build and use,
      so a common LAMP (Linux Apache MySQL Perl) platform was used, which also enables
      short development cycles. The application was built and tested using eXtreme
      Programming (XP) principles by a small development team consisting of one
      informatics specialist, one physician and one graphical designer/programmer.
      RESULTS: The parameter and graphical user interface (GUI) definitions for the
      CRIS can be made by non-IT professionals using an intuitive English-language-like
      formalism called application definition language (ADL). From these definitions,
      the MAGIC builds an end-user CRIS that can be used on a wide variety of platforms
      (from standard workstations to hand-held devices). A working example of a
      national health-care-quality assessment program is presented to illustrate this
      process. CONCLUSION: The lightweight application for generating CRIS (MAGIC) has
      proven to be useful for both clinical and analytical users in real working
      environment. To achieve better performance and interoperability, we are planning
      to recompile the application using XML schemas (XSD) in HL7 CDA or openEHR
      archetypes formats used for parameters definition and for data interchange
      between different information systems.

PMID- 25994876
TI  - Cardiovascular collapse after myocardial infarction due to centipede bite.
AB  - Centipede bites have been reported to cause localized and/or systemic symptoms
      including local pain, erythema and edema, nausea and vomiting, palpitations,
      headache, lymphadenopathy, and rhabdomyolysis. However, acute myocardial
      infarction due to centipede envenomation is reported in only three cases in
      English medical literature.We present a case of 31-year-old male bitten by a
      golden colored centipede leading to myocardial infarction and cardiopulmonary
      arrest which is seen very rarely. The patient was admitted to emergency
      department with a swollen and painful right foot. However, typical chest pain
      became the major complaint and cardiopulmonary arrest developed while
      electrocardiography was being obtained. The patient was resuscitated successfully
      for 5 min and acute infero-posterolateral myocardial infarction was detected on
      electrocardiography.

PMID- 25994875
TI  - The role of intraluminal thrombus formation for expansion of abdominal aortic
      aneurysms.
AB  - BACKGROUND: Though the pathophysiology of initiation, formation, and expansion of
      abdominal aortic aneurysm (AAA) has been intensely researched, the distinct
      mechanisms driving these processes still remain unclear. In particular, human
      studies on predictors of AAA progression as a major determinant of rupture risk
      are scarce. METHODS: All consecutive abdominal aortic ultrasound sonographic
      examinations performed at the duplex laboratory of the Division of Angiology of
      the Medical University of Vienna between 1999 and 2012 were reviewed. Patients
      with repeated measurements of the infrarenal aortic diameter, who had no prior
      AAA repair were included. Detailed informations on AAA, including length,
      anterior-posterior and transversal measurements of diameter, and intraluminal
      thrombus formation/size were obtained from ultrasound examination; patients'
      comorbidities, cardiovascular risk factors, and medications were obtained from
      outpatient charts. The expansion rate of AAA in relation to intraluminal thrombus
      size, gender, age, comorbidities, cardiovascular risk factors, and
      pharmacotherapy was evaluated. Independent predictors of AAA growth were
      identified through mixed effects models. RESULTS: In total, 166 patients (123 men
      and 43 women, mean age 68 +/- 9 years) were included. Patients were followed over
      a mean period of 1.4 +/- 1.2 years with a mean number of follow-up investigations
      of 4.4 +/- 2.7. Overall, mean maximum AAA diameter at baseline was 37.4 +/- 8.2
      mm. The average expansion rate of AAA diameter throughout the follow-up period
      was 2.0 mm per year (95 % confidence interval: 1.6-2.4). At initial
      investigation, intraluminal thrombus formation was present in 56.6 % of all
      patients. AAA diameter at baseline, time of follow-up as well as presence and
      size of intraluminal thrombus formation were identified as independent predictors
      of AAA expansion rate. Importantly, gender and presence of cardiovascular risk
      factors were not associated with AAA progression rate. CONCLUSIONS: Intraluminal
      thrombus formation seems to be a key determinant for progression of AAA diameter.
      Further prospective longitudinal studies are warranted to confirm the potential
      impact of thrombus formation on AAA development and its implication on monitoring
      and treatment decisions in patients with AAA.

PMID- 25994877
TI  - Sustained-release fluocinolone acetonide intravitreal insert for macular edema:
      clinical pharmacology and safety evaluation.
AB  - INTRODUCTION: Inflammation plays a key role in the pathological processes leading
      to macular edema. Sustained release, low-dose intraocular corticosteroid delivery
      devices provide long-term anti-inflammatory therapy. Recently, a novel
      fluocinolone acetonide intravitreal insert (FAi, Iluvien), has been introduced
      with promising long-term results in the treatment of macular edema. AREAS
      COVERED: An extensive review of the literature in the English language was
      performed to provide comprehensive information on the pharmacological properties
      of FAi and its safety and efficacy data from various multi-center randomized
      clinical trials. EXPERT OPINION: The FAc, Retisert is a sustained-release device
      that is surgically implanted in the vitreous and has been approved by the US FDA
      for the treatment of non-infectious intermediate, posterior or panuveitis. FAi
      was developed after FAc and is an intravitreal corticosteroid delivery system
      that allows controlled release of therapeutic levels of fluocinolone acetonide
      (FA). Initial efficacy and safety data suggest that this delivery system
      maintains clinical effectiveness for up to 3 years after a single delivery of the
      device. This second-generation fluocinolone delivery device has shown superior
      safety results in clinical trials compared to the previous version of the higher
      dose FAc (0.59 mg). Sustained delivery preparations may help to reduce the
      treatment burden and its associated risks by decreasing the frequency of
      intravitreal injections. However, much needs to be learnt from additional
      clinical trials, post-marketing surveillance and results of extension studies.
      Concerns of intravitreal corticosteroids, such as cataract and increase in
      intraocular pressure, remain major challenges for this therapeutic strategy.

PMID- 25994879
TI  - Maxillofacial Injury-Not Always a Difficult Airway.
AB  - The optimal method for securing the airway in injured patients is controversial.
      Maxillofacial injury has been shown to be a marker for difficult airway
      management; however, a delay in intubation may result in deterioration of
      intubating conditions due to further airway bleeding and swelling. Decisions on
      the timing and method of airway management depend on multiple factors, including
      patient characteristics, the skill set of the clinicians, and logistical
      considerations. This report describes the case of a multi-agency response to a
      motor-vehicle collision in a rural area in Ireland. One young male patient had
      sustained significant maxillofacial injuries, multiple limb injuries, and had a
      decreased level of consciousness. Further airway compromise occurred following
      extrication. Difficult intubation was predicted; however, abnormal jaw mobility
      from bilateral mandibular fractures enabled easy laryngoscopy and intubation.
      Although preparation must be made for difficult airway management in the setting
      of maxillofacial injury, appropriately trained and experienced practitioners
      should not be deterred from performing early intubation when indicated.

PMID- 25994878
TI  - Silver Nanoscale Hexagonal Column Chips for Detecting Cell-free DNA and
      Circulating Nucleosomes in Cancer Patients.
AB  - Blood tests, which are commonly used for cancer screening, generally have low
      sensitivity. Here, we developed a novel rapid and simple method to generate
      silver nanoscale hexagonal columns (NHCs) for use in surface-enhanced Raman
      scattering (SERS). We reported that the intensity of SERS spectra of clinical
      serum samples obtained from gastrointestinal cancer patients is was significantly
      higher than that of SERS spectra of clinical serum samples obtained from non
      cancer patients. We estimated the combined constituents on silver NHCs by using a
      field emission-type scanning electron microscope, Raman microscopes, and a 3D
      laser scanning confocal microscope. We obtained the Raman scattering spectra of
      samples of physically fractured cells and clinical serum. No spectra were
      obtained for chemically lysed cultured cells and DNA, RNA, and protein extracted
      from cultured cells. We believe that our method, which uses SERS with silver NHCs
      to detect circulating nucleosomes bound by methylated cell-free DNA, may be
      successfully implemented in blood tests for cancer screening. 

PMID- 25994881
TI  - Efficacy and safety of 0.1% kinetin cream in the treatment of photoaging skin.
AB  - BACKGROUND: Kinetin is a plant-derived compound, which is reported to possess
      antiaging properties. It has been used in a topical cream to manage facial photo
      damage and aging. Although studies elsewhere have shown its benefits, not many
      studies of the effects of kinetin in Asian skin are available. OBJECTIVES: To
      assess the efficacy and tolerability of 0.1% kinetin cream in the treatment of
      facial photo-aging. METHODS: The study was designed to be open-label and single
      blinded, without a control group. One hundred Thai female and male subjects with
      mild, moderate or severe facial photo-damage were enrolled. They were asked to
      apply 0.1% kinetin cream twice daily for 12 weeks and follow up at 4, 8, and 12
      weeks. Subjective patient self-assessment and physician assessment of facial skin
      photo-damage were accompanied by digital photographic analysis using the VISIA(r)
      (Canfield Scientific Inc, Fairfield, NJ) imaging system. RESULTS: At baseline,
      most patients reported moderate skin changes related to photo-damage, skin
      texture, skin color and wrinkles. After 12 weeks, physician and patient
      assessments showed slight but statistically significant improvements in overall
      skin condition, skin texture, color, and wrinkles. Findings were similar with the
      digital photographic system analysis, especially in relation to skin color.
      Facial ultraviolet spots and redness also showed statistically significant
      improvements after 12 weeks. The treatment was generally well tolerated.
      LIMITATIONS: The study was designed to be pragmatic and hence no randomization
      was carried out; there were also no intrapatient or interpatient control
      observations, and no comparison arm. CONCLUSION: Kinetin (0.1%) cream was found
      to slightly improve cutaneous facial photo-damage after 12 weeks of use in a
      group of Thai patients.

PMID- 25994880
TI  - Crystal structure of the fibre head domain of bovine adenovirus 4, a ruminant
      atadenovirus.
AB  - BACKGROUND: In adenoviruses, primary host cell recognition is generally performed
      by the head domains of their homo-trimeric fibre proteins. This first interaction
      is reversible. A secondary, irreversible interaction subsequently takes place via
      other adenovirus capsid proteins and leads to a productive infection. Although
      many fibre head structures are known for human mastadenoviruses, not many animal
      adenovirus fibre head structures have been determined, especially not from those
      belonging to adenovirus genera other than Mastadenovirus. METHODS: We constructed
      an expression vector for the fibre head domain from a ruminant atadenovirus,
      bovine adenovirus 4 (BAdV-4), consisting of amino acids 414-535, expressed the
      protein in Escherichia coli, purified it by metal affinity and cation exchange
      chromatography and crystallized it. The structure was solved using single
      isomorphous replacement plus anomalous dispersion of a mercury derivative and
      refined against native data that extended to 1.2 A resolution. RESULTS: Like in
      other adenoviruses, the BAdV-4 fibre head monomer contains a beta-sandwich
      consisting of ABCJ and GHID sheets. The topology is identical to the fibre head
      of the other studied atadenovirus, snake adenovirus 1 (SnAdV-1), including the
      alpha-helix in the DG-loop, despite of them having a sequence identity of only 15
      %. There are also differences which may have implications for ligand binding.
      Beta-strands G and H are longer and differences in several surface-loops and
      surface charge are observed. CONCLUSIONS: Chimeric adenovirus fibres have been
      used to retarget adenovirus-based anti-cancer and gene therapy vectors. Ovine
      adenovirus 7 (OAdV-7), another ruminant atadenovirus, is intensively tested as a
      basis for such a vector. Here, we present the high-resolution atomic structure of
      the BAdV-4 fibre head domain, the second atadenovirus fibre head structure known
      and the first of an atadenovirus that infects a mammalian host. Future research
      should focus on the receptor-binding properties of these fibre head domains.

PMID- 25994883
TI  - Cutaneous adverse events of epidermal growth factor receptor inhibitors: A
      retrospective review of 99 cases.
AB  - BACKGROUND: Previous reports regarding the cutaneous adverse events of epidermal
      growth factor receptor inhibitors are mostly limited to small case reports and
      case series, mainly involving Caucasian patients. AIMS: We describe the trends in
      the clinical presentation of Asian patients who had cutaneous adverse events
      induced by epidermal growth factor receptor inhibitors and to explore the
      relationship between skin adverse events and tumor response. METHODS: From 2006
      to 2010, medical records of Thai patients with non-small cell lung cancer
      receiving epidermal growth factor receptor inhibitors were retrieved and
      analyzed. RESULTS: In all, 99 patients were reviewed and analyzed. Erlotinib and
      gefitinib were commenced in 75 (75.8%) and 24 (24.2%) patients, respectively.
      Cutaneous adverse events occurred in 43 (57.3%) patients receiving erlotinib and
      in 15 (62.5%) patients receiving gefitinib. The most common adverse event was
      xerosis (52.5%). Less common adverse events included papulo-pustular eruption
      (27.3%), erythematous maculopapular rash (11.1%), mucositis (6.7%), paronychia
      (5.1%), and trichomegaly (2%). Elderly patients had a higher occurrence of
      xerosis. The presence of cutaneous adverse events was significantly higher in
      subjects who had a tumor response. LIMITATIONS: The limitations of study include
      its retrospective nature, and the initial screening of cutaneous adverse events
      was done by non-dermatologists. CONCLUSIONS: Cutaneous adverse events due to
      epidermal growth factor receptor inhibitors are not uncommon in the Asian
      population. We found a positive correlation between the occurrences of cutaneou
      adverse events and tumor response supporting the view that they are surrogate
      markers for therapeutic response.

PMID- 25994882
TI  - Cutaneous tuberculosis due to multidrug-resistant tubercle bacilli and
      difficulties in clinical diagnosis.
AB  - This report describes 6 HIV-negative patients including 5 children with
      scrofuloderma and an adult with lupus vulgaris, out of a total of 303 cases of
      cutaneous tuberculosis seen during a 41/2-year period, who showed a positive
      tuberculin test and granulomatous histopathology, but failed to respond to first
      line antitubercular therapy. They were suspected to have multidrug-resistant
      infection as no other cause could be ascertained. Tissue aspirate or biopsy was
      sent for histopathology and culture. Mycobacterium tuberculosis was isolated from
      the aspirate in three patients and sputum in one with associated pulmonary
      tuberculosis. Drug susceptibility tests showed that all isolates were resistant
      to rifampicin and isoniazid, and one each additionally to streptomycin and
      ethambutol, respectively. In two, culture was unsuccessful. All were administered
      second-line antitubercular drugs. Clinical improvement was appreciable within 2
      months as weight gain, and regression of ulcers, swellings and plaques. Two
      completed the recommended 24 months of therapy. Multidrug-resistant cutaneous
      tuberculosis should be suspected in patients with no response to first-line
      drugs, with clinical deterioration, and where other causes of treatment failure
      are not forthcoming. Owing to poor isolation rates on culture and low sensitivity
      of molecular tests, in such cases, a trial of second-line anti-tubercular drugs
      may be justified for a reasonable period of 2 months. Where facilities permit,
      culture and drug sensitivity tests should be done before starting treatment.
      Culture positivity is better from aspirated material. 

PMID- 25994884
TI  - Lipoid proteinosis.

PMID- 25994885
TI  - Bacillary angiomatosis presenting as a digital ulcer.

PMID- 25994886
TI  - Maffucci syndrome in an eight-year-old girl.

PMID- 25994887
TI  - Constricting band following incomplete condom removal.

PMID- 25994888
TI  - Extensive facial and vulval syringomas in a young woman.

PMID- 25994889
TI  - Primary amyloidosis.

PMID- 25994890
TI  - Cheilitis glandularis.

PMID- 25994893
TI  - Nevus lipomatosus superficialis associated with deep penetrating nevus.

PMID- 25994894
TI  - Primary localized cutaneous nodular amyloidosis with bullous lesions.

PMID- 25994895
TI  - Endonyx onychomycosis caused by Trichophyton tonsurans.

PMID- 25994896
TI  - Proliferating trichilemmal cyst with nodal enlargement mimicking metastatic
      squamous cell carcinoma.

PMID- 25994897
TI  - Cutaneous leishmaniasis mimicking verrucous carcinoma: A case with an unusual
      clinical course.

PMID- 25994898
TI  - Coexistence of multiple variants of porokeratosis.

PMID- 25994899
TI  - Doping of Zinc Oxide with Selected First Row Transition Metals for Photocatalytic
      Applications.
AB  - ZnO doped with Cr, Mn, Fe, Co, Ni and Cu was prepared by homogeneous hydrolysis
      of sulfates with urea. The samples were annealed at various temperatures and
      characterized by X-ray powder diffraction, UV/VIS reflectance spectroscopy, BET
      (Brunauer-Emmet-Teller) surface area and porosity measurements. The
      photocatalytic activity of the samples was evaluated by measuring the degradation
      of an organic dye Reactive Black 5. The morphology of the samples was determined
      by scanning electron microscopy and atomic force microscopy. For the Cu-doped ZnO
      sample, EPR spectra were obtained. All samples annealed at 800 degrees C
      contained hexagonal ZnO. In the VIS region, the best photocatalytic performance
      had the ZnO samples doped with Cr, Fe and Cu. 

PMID- 25994900
TI  - Characterization of a xylanase-producing Cellvibrio mixtus strain J3-8 and its
      genome analysis.
AB  - Cellvibrio mixtus strain J3-8 is a gram-negative, xylanase-producing aerobic soil
      bacterium isolated from giant snails in Singapore. It is able to produce up to
      10.1 U ml(-1) of xylanase, which is comparable to xylanase production from known
      bacterial and fungal strains. Genome sequence analysis of strain J3-8 reveals
      that the assembled draft genome contains 5,171,890 bp with a G + C content of
      46.66%, while open reading frame (ORF) annotations indicate a high density of
      genes encoding glycoside hydrolase (GH) families involved in (hemi)cellulose
      hydrolysis. On the basis of 15 identified putative xylanolytic genes, one
      metabolic pathway in strain J3-8 is constructed for utilization of xylan. In
      addition, a 1,083 bp xylanase gene from strain J3-8 represents a new member of
      GH11 family. This gene is verified to be novel via phylogenetic analysis. To
      utilize this novel gene for hydrolysis of xylan to xylose, it is expressed in
      recombinant E. coli and characterized for its hydrolytic activity. This study
      shows that strain J3-8 is a potential candidate for hydrolysis of lignocellulosic
      materials.

PMID- 25994901
TI  - Bioactive self-assembling lipid-like peptides as permeation enhancers for oral
      drug delivery.
AB  - Amphiphilic, lipid-like, self-assembling peptides are functional biomaterials
      with surfactant properties. In this work, lipid-like peptides were designed to
      have a hydrophilic head composed of aspartic acid or lysine and a six alanine
      residue hydrophobic domain and have a length similar to that of biological
      lipids. The aim of this work was to examine the potential of using ac-A6 K-CONH2
      , KA6 -CONH2 , ac-A6 D-COOH, and DA6 -COOH lipid-like peptides as permeability
      enhancers to facilitate transport through the intestinal barrier. In vitro
      transport studies of the macromolecular fluorescent marker fluorescein
      isothiocyanate (FITC)-dextran (4.4 kDa) through Caco-2 cell monolayers show the
      permeation enhancement ability of the lipid-like peptides. We observed increased
      FITC-dextran transport across the epithelial monolayer up to 7.6-fold in the
      presence of lipid-like peptides. Furthermore, we monitored the transepithelial
      resistance and performed immunofluorescence studies of the cell tight junctions.
      Ex vivo studies showed increased mucosal to serosal absorption of FITC-dextran in
      rat jejunum in the presence of the ac-A6 D-COOH peptide. Furthermore, a small
      increase in the serosal transport of bovine serum albumin was observed upon
      addition of ac-A6 D-COOH. Lipid-like peptides are biocompatible and they do not
      affect epithelial cell viability and epithelial monolayer integrity. Our results
      suggest that short, lipid-like peptides may be used as permeation enhancers to
      facilitate oral delivery of diagnostic and therapeutic molecules.

PMID- 25994902
TI  - Essential Role of Lysophosphatidylcholine Acyltransferase 3 in the Induction of
      Macrophage Polarization in PMA-Treated U937 Cells.
AB  - Lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty
      acid composition in biological membranes. Lysophosphatidylcholine
      acyltransferases (LPCATs) are members of the LPLATs that play a role in
      inflammatory responses. M1 macrophages differentiate in response to
      lipopolysaccharide (LPS) and are pro-inflammatory, whereas M2 macrophages, which
      differentiate in response to interleukin-4 (IL-4), are anti-inflammatory and
      involved in homeostasis and wound healing. In the present study, we showed that
      LPCATs play an important role in M1/M2-macrophage polarization. LPS changed the
      shape of PMA-treated U937 cells from rounded to spindle shaped and upregulated
      the mRNA and protein expression of the M1 macrophage markers CXCL10, TNF-alpha,
      and IL-1beta. IL-4 had no effect on the shape of PMA-treated U937 cells and
      upregulated the M2 macrophage markers CD206, IL-1ra, and TGF-beta in PMA-treated
      U937 cells. These results suggest that LPS and IL-4 promote the differentiation
      of PMA-treated U937 cells into M1- and M2-polarized macrophages, respectively.
      LPS significantly downregulated the mRNA expression of LPCAT3, one of four LPCAT
      isoforms, and suppressed its enzymatic activity toward linoleoyl-CoA and
      arachidonoyl-CoA in PMA-treated U937 cells. LPCAT3 knockdown induced a spindle
      shaped morphology typical of M1-polarized macrophages, and increased the
      secretion of CXCL10 and decreased the levels of CD206 in IL-4-activated U937
      cells. This indicates that knockdown of LPCAT3 shifts the differentiation of PMA
      treated U937 cells to M1-polarized macrophages. Our findings suggest that LPCAT3
      plays an important role in M1/M2-macrophage polarization, providing novel
      potential therapeutic targets for the regulation of immune and inflammatory
      disorders.

PMID- 25994904
TI  - The relationship of thoracic kyphosis to gait performance and quality of life in
      women with osteoporosis.
AB  - Thoracic kyphosis angle (TKA) increases with osteoporosis. This study aimed to
      investigate the relationship between magnitude of TKA and quality of life and
      gait performance in 34 osteoporotic women. Our results suggest that increasing
      TKA is significantly associated with decreasing quality of life (r = -0.48, p <
      0.005) and gait performance (r = -0.74, p < 0.0005). INTRODUCTION: Osteoporosis
      and its related effects are threatening health and quality of life especially in
      postmenopausal women. Increased thoracic kyphosis angle (TKA), as one of the most
      common adverse musculoskeletal changes, could be regarded as a quantitative index
      for osteoporotic patients' assessment. Dual digital inclinometer (DDI) is one of
      the latest tools for non-invasive TKA measurement. The main purpose of this study
      was to determine whether a relationship existed between the magnitude of TKA,
      gait performance, and quality of life in a group of osteoporotic women. METHODS:
      Thirty-four osteoporotic women, aged 50-68, participated in this descriptive
      analytic study. The magnitude of TKA measured by using DDI and expressed as the
      kyphosis index (KI). Quality of life and gait performance were assessed using
      short form 36 (SF36) questionnaire and functional gait assessment test,
      respectively. Back extension range of motion (ROM) and back extensor strength
      were also assessed. Pearson's correlation test was used to analyze the data, with
      the significance level of p < 0.05. RESULTS: The findings revealed a
      statistically significant negative correlation between KI and quality of life (r
      = -0.48, p < 0.005) and KI and gait performance (r = -0.74, p < 0.0005). There
      was also a significantly negative relation between KI and back extension ROM and
      back extensor strength (p < 0.05). CONCLUSION: The results of this study
      demonstrated that increased thoracic kyphosis negatively affects gait performance
      and quality of life. This finding could be regarded as an important implication
      for therapist to pay more attention to the magnitude of thoracic kyphosis angle
      and its changes, when selecting appropriate therapeutic methods to improve gait
      performance and quality of life in osteoporosis women.

PMID- 25994907
TI  - [Informed consent analysis and its role in modern medicine].
AB  - "Informed consent" is a term adopted by the contemporary medicine in all its
      fields. There may seem that it is a plain rendering of information to the patient
      followed by her/his decision about further procedures but the facts are
      different. Actually this relationship between patient and doctor has an intricate
      nature. It guarantees an ethical frame and structure of any treatment afforded to
      the patient and it covers all the possible dilemmas as conflicts of any two
      principles taken from any contemporary medical code while it allows no simple
      resolution. Individual steps require a compromise based on continuous discussion
      between both sides. In this process means controlled by the doctor and patients
      goals must be conscientiously distinguished since a goal or meaning of live is
      not an expertise of the doctor and the doctor is obliged solely to revere them
      whereas to develop means or tools (organon) in all its manners is on the other
      side her/his main task. 

PMID- 25994908
TI  - [Positive aspects of old ages - humor of seniors].
AB  - This survey study has five parts. In the first part two conceptual approaches to
      humor are characterized. One considers "the comic" to be an umbrella concept, and
      humor is only one of its rather positive forms. The other comes out from the
      umbrella concept "humor", and distinguishes between various forms of humor
      including the negative ones. Three main theories of humor are presented: theory
      of superiority, theory of incongruity, and a relief theory. The second part
      introduces humor in the elderly and draws the attention to the fact that we know
      relatively little about humor in old age because most research has been carried
      out in children, adolescents or adults in productive age. The third part of the
      study describes the process of diagnostics of humor in the elderly. For example,
      within the qualitative methods, in-depth interviews with seniors or analyses of
      their diary entries are used. Within quantitative methods, questionnaires are
      used, and this study presents the survey of seven most frequent ones applied in
      the studies of humor in the elderly. In the context of mixed methods,
      understanding of humor in young and seniors, or understanding of humor in
      relatively healthy seniors and seniors after stroke are compared. The fourth part
      of the study presents the Gelkopfs model on relationship between humor, treatment
      and cure of patients. The fifth part of the study demonstrates the options how to
      use humor to improve the mental state of the elderly (by means of individual or
      group interventions). 

PMID- 25994905
TI  - Effect of whole body vibration training on bone mineral density and bone quality
      in adolescents with Down syndrome: a randomized controlled trial.
AB  - Adolescents with Down syndrome (DS) have poorer bone health than their peers
      without DS. Twenty-five adolescents with DS were randomly assigned to whole-body
      vibration training (WBV) or control groups. The results indicate that a 20-week
      WBV might be useful to improve subtotal bone mineral content and density in
      adolescents with DS. INTRODUCTION: This study aims to determine the effects of 20
      weeks of whole body vibration training (WBV) on bone mineral content (BMC),
      density (BMD), and structure variables in adolescents with Down syndrome (DS).
      METHODS: This randomized controlled trial of 25 adolescents (12-18 years) with DS
      (8 females) generated 2 non-equal groups, WBV group (n = 11) and CON group (n =
      14). Using an efficacy analysis, the primary outcomes were BMC and BMD by dual
      energy X-ray absorptiometry and the secondary were bone structure variables by
      peripheral quantitative computed tomography. A synchronous vibration platform
      (PowerPlate(r)) was used (3/week, 10 repetitions (30-60 s) 1-min rest, frequency
      of 25-30 Hz, and peak-to-peak displacement of 2 mm (peak acceleration 2.5-3.6
      g)). RESULTS: WBV group improved whole body BMC 2.8%, 95% CI [3.5, 2.1], subtotal
      area, BMC, and BMD by 2.8, 4.8, and 2%, respectively, 95% confidence intervals
      (CIs) [3.4, 2.1], [6.5, 3.1], and [2.8, 1.1], respectively (all, p < 0.05),
      showing group by time interactions in BMC and BMD (both p < 0.05). Lumbar spine
      BMC and BMD also increased in the WBV group by 6.6 and 3.3% both p < 0.05, 95 %
      CIs [8.6, 4.7], and [4.9, 1.7], respectively. Regarding bone structure, WBV group
      showed improvements in tibial BMC at 4 % (2.9 %, 95 % CI [3.0, 2.8]) and in
      volumetric BMD (vBMD), cortical vBMD, and cortical thickness at 66% of the radius
      (by 7.0, 2.4, and 10.9%; 95% CIs [7.4, 6.7], [2.6, 2.3], and [12.4, 9.3],
      respectively) (all, p < 0.05). CONCLUSIONS: A 20-week WBV, with this protocol,
      might be useful to improve subtotal BMC and BMD in adolescents with DS.

PMID- 25994909
TI  - [Use of pulmonary rehabilitation in the treatment of decreased respiratory muscle
      strength].
AB  - Decreased respiratory muscle strength could lead to other health problems, which
      can decrease the quality of life of those patients. Ineffective expectoration and
      dyspnoea during physical activities and during activity of daily living are the
      most frequent disorders associated with decreased respiratory muscle strength.
      Multidisciplinary treatment including pulmonary rehabilitation programme is very
      important for those patients. Ventilatory muscle training (strength and endurance
      type of training), airway clearance techniques - active (e.g. autogenic drainage,
      instrumental techniques) and passive (e.g. manual thoracic compression,
      mechanical insufflator/exsufflator machine) and exercise training are the most
      frequent used techniques in these patients. Assessment of all respiratory muscles
      function - especially their respiratory and postural function - is important at
      the beginning of rehabilitation treatment. 

PMID- 25994911
TI  - [Female androgenetic alopecia, a survey of causes and therapeutic options].
AB  - Mesotherapy is one of the options for the treatment of androgenetic alopecia.
      Testing 24 women with androgenetic alopecia has demonstrated a positive effect of
      mesotherapy on the hair growth, hair thickness, with only insignificant increase
      of hair density. It is known that androgenetic alopecia represents a localized
      aging of hair follicles. We therefore decided to examine the different effects of
      mesotherapy on hair density in younger and in elderly women. In younger women
      mesotherapy significantly increased hair density compared with older women. For
      mesotherapy we used a combination of micronutrients and antioxidants. Mesotherapy
      achievements were evident for 6-12 months. Treatment requires a long-term care. 

PMID- 25994910
TI  - [The prospects for children with acute lymphoblastic leukemia of being cured has
      increased in the Czech Republic in the 21st century to 90% - outcome of the ALL
      IC BFM 2002 trial].
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequent childhood
      malignancy. Treatment has been unified in the middle of 1980 in the Czech
      Republic. In 2002-2007 children and adolescents with acute lymphoblastic leukemia
      were treated in an international randomized trial ALL-IC BFM 2002 in the Czech
      Republic. 291 patients aged 1-18 years were enrolled; infants below 1 year
      entered a separate trial. METHODS AND RESULTS: Patients were stratified into
      three risk groups according to their age, initial leukocyte count, prednisone
      response, presence of fusion genes BCR/ABL or MLL/AF4, bone marrow D+15 and
      remission status D+33. The whole therapy took 24 months. Randomized late
      intensification compared standard BFM therapy with extended, usually more
      intensive experimental treatment. The median follow-up was 8.7 years. Complete
      remission was achieved in 97.9% patients, 1% died in remission. 11% of children
      relapsed, 1.7% with CNS involvement. Six children (2.1%) developed secondary
      malignancy. Event free survival (EFS) 8 years from diagnosis was 83.5%, overall
      survival (OS) 91.4%. EFS and OS of the risk groups were: standard risk: 89.4%;
      98.1%; intermediate risk: 82.6%; 89.6%; high risk: 68.8%; 78.1%. Male sex and age
      above 10 years were adverse prognostic factors. CONCLUSIONS: In comparison with
      the previous trial ALL-BFM 95, significant improvement was achieved.

PMID- 25994912
TI  - [Wenzel Leopold Gruber (1814-1890)].
AB  - Gruber was born in Krukanice, a small village near to Pilsen on September 24,
      1814. He started his medical studies in Prague at 1834. He became doctor of
      surgery in 1842, and in 1844 was conferred doctor of medicine. He was prosector
      of normal anatomy at the University of Prague in 1842-1847. Although qualified,
      he was unable to achieve a professorship in his native country. Therefore, in
      1846, on the initiative of Pirogov, he was invited to become the first prosector
      for normal, practical, and pathological anatomy at the Medical Academy in St.
      Petersburg. From 1855, Gruber was entrusted the directorship of practical
      anatomy, remaining at that position for some 30 years. He died on September 30
      1890 of stroke in Vienna. Gruber played an active role in the establishment of
      the anatomical-physiological institute in Petersburg and founded here a museum.
      As one of the most experienced and active anatomists, Gruber published, over a
      period of 41 years, almost 500 scientific works. 

PMID- 25994913
TI  - Functional Mechanism(s) of the Inhibition of Disease Progression by Combination
      Treatment with Fingolimod Plus Pathogenic Antigen in a Glucose-6-phosphate
      Isomerase Peptide-Induced Arthritis Mouse Model.
AB  - We previously reported that combination treatment with fingolimod (FTY720) plus
      antigenic peptide of glucose-6-phosphate isomerase (residues 325-339) (GPI325
      339) from the onset of symptoms significantly inhibited disease progression in a
      mouse model of GPI325-339-induced arthritis. In this study, we investigated the
      mechanism(s) involved. The model mice were treated from arthritis onset with
      FTY720 alone, GPI325-339 alone, or the combination of FTY720 plus GPI325-339. At
      the end of treatment, inguinal lymph nodes (LNs) were excised and examined
      histologically and in flow cytometry. Levels of apoptotic cells, programmed death
      1-expressing CD4(+)forkhead box P3(-) nonregulatory T cells (non-Tregs), and
      cytotoxic T-lymphocyte antigen 4-expressing non-Tregs in inguinal LNs were
      markedly increased in the combination treatment group mice. Regulatory T cells
      (Tregs) were also increased. These results indicate that combination treatment
      with FTY720 plus GPI325-339 inhibits the progression of arthritis by inducing
      clonal deletion and anergy of pathogenic T cells and also by immune suppression
      via Tregs. 

PMID- 25994914
TI  - Quantitative Analysis of Glutamate Receptors in Glial Cells from the Cortex of
      GFAP/EGFP Mice Following Ischemic Injury: Focus on NMDA Receptors.
AB  - Cortical glial cells contain both ionotropic and metabotropic glutamate
      receptors. Despite several efforts, a comprehensive analysis of the entire family
      of glutamate receptors and their subunits present in glial cells is still
      missing. Here, we provide an overall picture of the gene expression of ionotropic
      (AMPA, kainate, NMDA) and the main metabotropic glutamate receptors in cortical
      glial cells isolated from GFAP/EGFP mice before and after focal cerebral
      ischemia. Employing single-cell RT-qPCR, we detected the expression of genes
      encoding subunits of glutamate receptors in GFAP/EGFP-positive (GFAP/EGFP(+))
      glial cells in the cortex of young adult mice. Most of the analyzed cells
      expressed mRNA for glutamate receptor subunits, the expression of which, in most
      cases, even increased after ischemic injury. Data analyses disclosed several
      classes of GFAP/EGFP(+) glial cells with respect to glutamate receptors and
      revealed in what manner their expression correlates with the expression of glial
      markers prior to and after ischemia. Furthermore, we also examined the protein
      expression and functional significance of NMDA receptors in glial cells.
      Immunohistochemical analyses of all seven NMDA receptor subunits provided direct
      evidence that the GluN3A subunit is present in GFAP/EGFP(+) glial cells and that
      its expression is increased after ischemia. In situ and in vitro Ca(2+) imaging
      revealed that Ca(2+) elevations evoked by the application of NMDA were diminished
      in GFAP/EGFP(+) glial cells following ischemia. Our results provide a
      comprehensive description of glutamate receptors in cortical GFAP/EGFP(+) glial
      cells and may serve as a basis for further research on glial cell physiology and
      pathophysiology. 

PMID- 25994915
TI  - Flavobacterium nitrogenifigens sp. nov., isolated from switchgrass (Panicum
      virgatum).
AB  - A yellow, nitrogen-fixing bacterial strain, NXU-44(T), isolated from the
      rhizosphere of switchgrass (Panicum virgatum) in Auburn, Alabama, USA, was
      studied to determine its taxonomic position. Cells of the isolate were rod-shaped
      and Gram-stain-negative. A comparison of the 16S rRNA gene sequence with the
      sequences of the type strains of the most closely related species showed that the
      strain belongs to the genus Flavobacterium with highest sequence similarities to
      the type strains of Flavobacterium ginsenosidimutans (97.9%), Flavobacterium
      phragmitis (97.6%) and Flavobacterium anhuiense (97.5%). The 16S rRNA gene
      sequence similarities to all other species of the genus Flavobacterium were below
      97.5%. The fatty acid profile of strain NXU-44(T) consisted of the major fatty
      acids iso-C15 : 0, iso-C15 : 0 2-OH/C16 : 1omega7c and iso-C17 : 0 3-OH. The
      major compounds in the polar lipid profile were phosphatidylethanolamine,
      phosphatidylserine, one aminolipid and two polar lipids. The quinone system was
      composed exclusively of menaquinone MK-6. The polyamine pattern contained the
      major compound sym-homospermidine and only minor amounts of other polyamines. The
      diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid. These
      data and the differential biochemical and chemotaxonomic properties show that
      strain NXU-44(T) represents a novel species of the genus Flavobacterium for which
      the name Flavobacterium nitrogenifigens sp. nov. is proposed. The type strain is
      NXU-44(T) ( = LMG 28694(T) = CIP 110894(T)).

PMID- 25994916
TI  - Reverse genetics of rabies virus: new strategies to attenuate virus virulence for
      vaccine development.
AB  - Rabies is an ancient neurological disease that is almost invariably fatal once
      the clinical symptoms develop. Currently, prompt wound cleansing after exposing
      to a potentially rabid animal and vaccination using rabies vaccine combined with
      administration of rabies immune globulin are the only effective methods for post
      exposure prophylaxis against rabies. Reverse genetic technique is a novel
      approach to investigate the function of a specific gene by analyzing the
      phenotypic effects through directly manipulating the gene sequences. It has
      revolutionized and provided a powerful tool to study the molecular biology of RNA
      viruses and has been widely used in rabies virus research. The attenuation of
      rabies virus virulence is the prerequisite for rabies vaccine development. Given
      the current challenge that sufficient and affordable high-quality vaccines are
      limited and lacking for global rabies prevention and control, highly cell
      adapted, stable, and attenuated rabies viruses with broad cross-reactivity
      against different viral variants are ideal candidates for consideration to meet
      the need for human rabies control in the future. A number of approaches have been
      pursued to reduce the virulence of the virus and improve the safety of rabies
      vaccines. The application of reverse genetic technique has greatly advanced the
      engineering of rabies virus and paves the avenue for utilizing rabies virus for
      vaccine against rabies, viral vectors for exogenous antigen expression, and gene
      therapy in the future. 

PMID- 25994917
TI  - Diabolical effects of rabies encephalitis.
AB  - Rabies is an acute encephalomyelitis in humans and animals caused by rabies virus
      (RABV) infection. Because the neuropathological changes are very mild in rabies,
      it has been assumed that neuronal dysfunction likely explains the severe clinical
      disease. Recently, degenerative changes have been observed in neuronal processes
      (dendrites and axons) in experimental rabies. In vitro studies have shown
      evidence of oxidative stress that is caused by mitochondrial dysfunction. Recent
      work has shown that the RABV phosphoprotein (P) interacts with mitochondrial
      Complex I leading to overproduction of reactive oxygen species, which results in
      injury to axons. Amino acids at positions 139 to 172 of the P are critical in
      this process. Rabies vectors frequently show behavioral changes. Aggressive
      behavior with biting is important for transmission of the virus to new hosts at a
      time when virus is secreted in the saliva. Aggression is associated with low
      serotonergic activity in the brain. Charlton and coworkers performed studies in
      experimentally infected striped skunks with skunk rabies virus and observed
      aggressive behavioral responses. Heavy accumulation of RABV antigen was found in
      the midbrain raphe nuclei, indicating that impaired serotonin neurotransmission
      from the brainstem may account for the aggressive behavior. We now have an
      improved understanding of how RABV causes neuronal injury and how the infection
      results in behavioral changes that promote viral transmission to new hosts. 

PMID- 25994919
TI  - Graphene oxide membranes with tunable semipermeability in organic solvents.
AB  - Graphene oxide membranes (GOMs) are mechanically stable in various organic
      solvents, and their nanochannels can be narrowed by thermal annealing or widened
      by solvation. Therefore, the semipermeability of GOMs can be easily modulated,
      and they can be used as "multipurpose membranes" for molecular sieving in organic
      media. 

PMID- 25994918
TI  - Microstructural parameter estimation in vivo using diffusion MRI and structured
      prior information.
AB  - PURPOSE: Diffusion MRI has recently been used with detailed models to probe
      tissue microstructure. Much of this work has been performed ex vivo with powerful
      scanner hardware, to gain sensitivity to parameters such as axon radius. By
      contrast, performing microstructure imaging on clinical scanners is extremely
      challenging. METHODS: We use an optimized dual spin-echo diffusion protocol, and
      a Bayesian fitting approach, to obtain reproducible contrast (histogram overlap
      of up to 92%) in estimated maps of axon radius index in healthy adults at a
      modest, widely-available gradient strength (35 mT m(-1)). A key innovation is the
      use of influential priors. RESULTS: We demonstrate that our priors can improve
      precision in axon radius estimates--a 7-fold reduction in voxelwise coefficient
      of variation in vivo--without significant bias. Our results may reflect true axon
      radius differences between white matter regions, but this interpretation should
      be treated with caution due to the complexity of the tissue relative to our
      model. CONCLUSIONS: Some sensitivity to relatively large axons (3-15 MUm) may be
      available at clinical field and gradient strengths. Future applications at higher
      gradient strength will benefit from the favorable eddy current properties of the
      dual spin-echo sequence, and greater precision available with suitable priors.
      Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance.

PMID- 25994920
TI  - Oral Cavity Clear Cell Odontogenic Carcinoma.
AB  - A case of clear cell odontogenic carcinoma of the oral cavity is described in
      this sine qua non radiology-pathology correlation article. CT demonstrated a
      solid and cystic mass arising from the mandible. Histology demonstrated variably
      sized nests of clear to pale eosinophilic cells with occasional central necrosis
      embedded in a hyalinized to fibrocellular stroma. The specimen was also positive
      for the characteristic rearrangement of the EWSR1 (22q12) locus in 93.5% of
      interphase cells.

PMID- 25994921
TI  - Microscopic dynamics of synchronization in driven colloids.
AB  - Synchronization of coupled oscillators has been scrutinized for over three
      centuries, from Huygens' pendulum clocks to physiological rhythms. One such
      synchronization phenomenon, dynamic mode locking, occurs when naturally
      oscillating processes are driven by an externally imposed modulation. Typically
      only averaged or integrated properties are accessible, leaving underlying
      mechanisms unseen. Here, we visualize the microscopic dynamics underlying mode
      locking in a colloidal model system, by using particle trajectories to produce
      phase portraits. Furthermore, we use this approach to examine the enhancement of
      mode locking in a flexible chain of magnetically coupled particles, which we
      ascribe to breathing modes caused by mode-locked density waves. Finally, we
      demonstrate that an emergent density wave in a static colloidal chain mode locks
      as a quasi-particle, with microscopic dynamics analogous to those seen for a
      single particle. Our results indicate that understanding the intricate link
      between emergent behaviour and microscopic dynamics is key to controlling
      synchronization. 

PMID- 25994922
TI  - Judgmental Biases of Individuals with a Fear of Blushing: The Role of Relatively
      Strict Social Norms.
AB  - Blushing-fearful individuals often expect that others will judge them negatively.
      In two studies, we tested if this could be explained by having relatively strict
      beliefs about what is appropriate social behaviour. Study 1 used a student sample
      (n = 74), whereas study 2 compared a clinical treatment-seeking sample of
      blushing-fearful individuals (n = 33) with a non-anxious control group (n = 31).
      In both studies, participants were asked to read descriptions of common
      behaviours that could be considered as breaching the prevailing social norms but
      not necessarily so. Participants indicated (i) to what extent they considered
      these behaviours as violating the prevailing norm and (ii) their expectation of
      observers' judgments. Study 1 showed that strict norms were indeed related to
      fear of blushing and that the tendency of fearful participants to expect negative
      judgments could at least partly explain this relationship. Study 2 showed that
      high-fearful and low-fearful individuals do indeed differ in the strictness of
      their norms and that especially the norms that individuals apply to themselves
      might be relevant. These findings may provide fresh clues for improving available
      treatment options. KEY PRACTITIONER MESSAGES: Blushing-fearful individuals
      attribute relatively strict social norms to other people about which behaviours
      are appropriate and which are not and have stricter personal norms as well.
      Blushing-fearful individuals' tendency to expect overly negative judgments in
      ambivalent social situations can partly be explained by their relatively strict
      social norms. Having relatively strict social norms may (also) explain why
      blushing-fearful individuals report to blush often and intensely. It may be
      worthwhile to address strict social norms in therapy for fear of blushing.

PMID- 25994923
TI  - PET Imaging of Serotonin Transporters With 4-[(18)F]-ADAM in a Parkinsonian Rat
      Model With Porcine Neural Xenografts.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss
      of dopaminergic neurons in the nigrostriatal pathway. Apart from effective
      strategies to halt the underlying neuronal degeneration, cell replacement now
      offers novel prospects for PD therapy. Porcine embryonic neural tissue has been
      considered an alternative source to human fetal grafts in neurodegenerative
      disorders because its use avoids major practical and ethical issues. This study
      was undertaken to evaluate the effects of embryonic day 27 (E27) porcine
      mesencephalic tissue transplantation in a PD rat model using animal positron
      emission tomography (PET) coupled with 4-[(18)F]-ADAM, a serotonin transporter
      (SERT) imaging agent. The parkinsonian rat was induced by injecting 6
      hydroxydopamine into the medial forebrain bundle (MFB) of the right nigrostriatal
      pathway. The apomorphine-induced rotation behavioral test and 4-[(18)F]
      ADAM/animal PET scanning were carried out following 6-OHDA lesioning. At the
      second week following 6-OHDA lesioning, the parkinsonian rat rotates
      substantially on apomorphine-induced contralateral turning. In addition, the mean
      striatal-specific uptake ratio (SUR) of 4-[(18)F]-ADAM decreased by 44%. After
      transplantation, the number of drug-induced rotations decreased markedly, and the
      mean SUR of 4-[(18)F]-ADAM and the level of SERT immunoreactivity (SERT-ir) in
      striatum were partially restored. The mean SUR level was restored to 71% compared
      to that for the contralateral intact side, which together with the abundant
      survival of tyrosine hydroxylase (TH) neurons accounted for functional recovery
      at the fourth week postgraft. In regard to the extent of donor-derived cells, we
      found the neurons of the xenografts from E27 transgenic pigs harboring red
      fluorescent protein (RFP) localized with TH-ir cells and SERT-ir in the grafted
      area. Thus, transplanted E27 porcine mesencephalic tissue may restore
      dopaminergic and serotonergic systems in the parkinsonian rat. The 4-[(18)F]
      ADAM/animal PET can be used to detect serotonergic neuron loss in PD and monitor
      the efficacy of therapy. 

PMID- 25994924
TI  - Sleep apnea and venous thromboembolism. A systematic review.
AB  - Recent evidence suggests that obstructive sleep apnea is a significant and
      independent risk factor for a number of cardiovascular disorders. Since the
      association between obstructive sleep apnea and cardiovascular disease is
      mediated by endothelial dysfunction, hypercoagulability and platelet
      abnormalities, we sought to investigate whether sleep apnea may also be
      considered a risk factor for venous thromboembolism (VTE). We carried out an
      electronic search in Medline and Scopus using the keywords "apnea" OR "apnoea"
      AND "venous thromboembolism" OR "deep vein thrombosis" OR "pulmonary embolism" in
      "Title/Abstract/Keywords", with no language or date restriction. Fifteen studies
      (8 case-control, 4 retrospective observational, 2 prospective case-control and 1
      prospective observational) were finally selected for this systematic review. In
      all studies except one (14/15; 93 %), obstructive sleep apnea was found to be an
      independent risk factor for VTE, either deep-vein thrombosis (DVT) or pulmonary
      embolism (PE). In the two prospective case-control studies the risk of DVT or PE
      was found to be two- to three-fold higher in patients with obstructive sleep
      apnea than in those without. In conclusion, the current epidemiological evidence
      supports the hypothesis that obstructive sleep apnea may be an independent risk
      factor for VTE. 

PMID- 25994925
TI  - Directed self-assembly of gold nanoparticles into plasmonic chains.
AB  - The plasmonic behavior of metals at the nanoscale is not only appealing for
      fundamental studies, but also very useful for the development of innovative
      photonic devices. The past few decades have witnessed great progress in colloidal
      synthesis of monodisperse metal nanoparticles with defined shapes. This has
      significantly fueled up the research of directing the metal nanoparticles to self
      assemble into tailored extended structures, especially low dimensional ones, for
      a better control and manipulation of the interactions of the metal nanoparticles
      with light. In parallel, theories for a better description of nanoplasmonics have
      been increasingly developed and improved. Thus, the present review is focused on
      the overview of current experimental and theoretical developments in the directed
      self-assembly of metal nanoparticles with tailored plasmonic properties, which,
      hopefully, will provide useful guidelines for future research studies and
      applications of nanoplasmonics. 

PMID- 25994926
TI  - Microfluidic wound model for studying the behaviors of Pseudomonas aeruginosa in
      polymicrobial biofilms.
AB  - Pseudomonas aeruginosa is a particularly problematic opportunistic pathogen due
      to its capacity to form recalcitrant biofilm structures, while cohabiting with
      other harmful/pathogenic species and harboring the capability to release toxins
      that cause tissue necrosis. Although it is now recognized that the majority of
      biofilm infections are polymicrobial, little is known about the complex
      interactions that occur within polymicrobial communities and few tools exist for
      studying these interactions. In this study, we have designed a microfluidic model
      that mimics the relevant physiological properties of wound microenvironment,
      while incorporating materials present in the human extracellular matrix/wound
      environment. Using microfluidics combined with imaging techniques, we have
      validated the robustness of our model comparing traditional GFP-tagging to new
      fluorescent staining techniques to visualize/resolve individual species within a
      polymicrobial habitat. We have also demonstrated that chemotactic stimuli may be
      incorporated into our model through specialized ports in our chamber. Our system
      is specifically designed for use with high resolution imaging techniques,
      allowing for data collection throughout the life of the biofilm and in real-time.
      Ultimately, this model can be used to investigate the spatio-temporal
      mechanobiological structures of the wound environment, and the response of the
      bacteria to the drug transport which will significantly contribute to our
      understanding of the development and progression of polymicrobial biofilm
      infections.

PMID- 25994927
TI  - The Role of Human Factors/Ergonomics in the Science of Security: Decision Making
      and Action Selection in Cyberspace.
AB  - OBJECTIVE: The overarching goal is to convey the concept of science of security
      and the contributions that a scientifically based, human factors approach can
      make to this interdisciplinary field. BACKGROUND: Rather than a piecemeal
      approach to solving cybersecurity problems as they arise, the U.S. government is
      mounting a systematic effort to develop an approach grounded in science. Because
      humans play a central role in security measures, research on security-related
      decisions and actions grounded in principles of human information-processing and
      decision-making is crucial to this interdisciplinary effort. METHOD: We describe
      the science of security and the role that human factors can play in it, and use
      two examples of research in cybersecurity--detection of phishing attacks and
      selection of mobile applications--to illustrate the contribution of a scientific,
      human factors approach. RESULTS: In these research areas, we show that systematic
      information-processing analyses of the decisions that users make and the actions
      they take provide a basis for integrating the human component of security
      science. CONCLUSION: Human factors specialists should utilize their foundation in
      the science of applied information processing and decision making to contribute
      to the science of cybersecurity.

PMID- 25994928
TI  - [Obstructive shock].
AB  - An acute obstruction of blood flow in central vessels of the systemic or
      pulmonary circulation causes the clinical symptoms of shock accompanied by
      disturbances of consciousness, centralization, oliguria, hypotension and
      tachycardia. In the case of an acute pulmonary embolism an intravascular
      occlusion results in an acute increase of the right ventricular afterload. In the
      case of a tension pneumothorax, an obstruction of the blood vessels supplying the
      heart is caused by an increase in extravascular pressure. From a hemodynamic
      viewpoint circulatory shock caused by obstruction is closely followed by cardiac
      deterioration; however, etiological and therapeutic options necessitate
      demarcation of cardiac from non-cardiac obstructive causes. The high dynamics of
      this potentially life-threatening condition is a hallmark of all types of
      obstructive shock. This requires an expeditious and purposeful diagnosis and a
      rapid and well-aimed therapy. 

PMID- 25994929
TI  - Advantages of new technologies in oral mucosal surgery: an intraoperative
      comparison among Nd:YAG laser, quantic molecular resonance scalpel, and cold
      blade.
AB  - The aim of this study is to evaluate the possible intraoperative advantages of
      Nd:YAG laser and quantic molecular resonance (QMR) scalpel in oral soft tissue
      surgery. One hundred sixty-three interventions were evaluated. Group 1 (G1)
      included 77 interventions performed with Nd:YAG laser, group 2 (G2) 45 with QMR
      scalpel, and group 3 (G3) 41 with cold blade. Parameters analyzed were as
      follows: speed of incision, time of intervention, intraoperative bleeding, number
      of stitches, patient compliance, and operator comfort. Data were analyzed using
      software STATA 12 (StataCorp LP, College Station, TX, USA). Mean speed of
      incision was 0.54 mm/s in G1, 2.83 mm/s in G2, and 1.58 mm/s in G3, Nd:YAG laser
      being the slowest. However, no significant differences among times of
      intervention were found. In particular, interventions in G1 (221.15 +/- 220.89 s)
      have a mean duration lower than G2 (280.56 +/- 248.31 s) and G3 (316.10 +/-
      248.69 s). Intraoperative bleeding occurred in 29.9 % (n = 23/77) of
      interventions in G1, 97.8 % (n = 44/45) in G2, and 97.6 % (n = 40/41) in G3 (p <
      0.0001). Mean number of stitches in G1 was statistically lower (G1, 0.10; G2,
      2.07; G3, 2.29; p < 0.0001). No differences with regard to patient compliance
      were detected. Operator comfort was higher in G1 (p < 0.0003). Nd:YAG laser and
      QMR scalpel give several advantages in oral mucosal surgery: Nd:YAG laser cuts
      tissue slowly, but it provides a good visibility and excellent hemostasis. QMR
      scalpel allows a very rapid cutting with no considerable temperature increase,
      but there is major risk of bleeding and need for sutures with lower operator
      comfort.

PMID- 25994930
TI  - Genome-Wide Analysis in Three Fusarium Pathogens Identifies Rapidly Evolving
      Chromosomes and Genes Associated with Pathogenicity.
AB  - Pathogens and hosts are in an ongoing arms race and genes involved in host
      pathogen interactions are likely to undergo diversifying selection. Fusarium
      plant pathogens have evolved diverse infection strategies, but how they interact
      with their hosts in the biotrophic infection stage remains puzzling. To address
      this, we analyzed the genomes of three Fusarium plant pathogens for genes that
      are under diversifying selection. We found a two-speed genome structure both on
      the chromosome and gene group level. Diversifying selection acts strongly on the
      dispensable chromosomes in Fusarium oxysporum f. sp. lycopersici and on distinct
      core chromosome regions in Fusarium graminearum, all of which have associations
      with virulence. Members of two gene groups evolve rapidly, namely those that
      encode proteins with an N-terminal [SG]-P-C-[KR]-P sequence motif and proteins
      that are conserved predominantly in pathogens. Specifically, 29 F. graminearum
      genes are rapidly evolving, in planta induced and encode secreted proteins,
      strongly pointing toward effector function. In summary, diversifying selection in
      Fusarium is strongly reflected as genomic footprints and can be used to predict a
      small gene set likely to be involved in host-pathogen interactions for
      experimental verification. 

PMID- 25994931
TI  - Dual Organellar Targeting of Aminoacyl-tRNA Synthetases in Diatoms and
      Cryptophytes.
AB  - The internal compartmentation of eukaryotic cells not only allows separation of
      biochemical processes but it also creates the requirement for systems that can
      selectively transport proteins across the membrane boundaries. Although most
      proteins function in a single subcellular compartment, many are able to enter two
      or more compartments, a phenomenon known as dual or multiple targeting. The
      aminoacyl-tRNA synthetases (aaRSs), which catalyze the ligation of tRNAs to their
      cognate amino acids, are particularly prone to functioning in multiple
      subcellular compartments. They are essential for translation, so they are
      required in every compartment where translation takes place. In diatoms, there
      are three such compartments, the plastid, the mitochondrion, and the cytosol. In
      cryptophytes, translation also takes place in the periplastid compartment (PPC),
      which is the reduced cytoplasm of the plastid's red algal ancestor and which
      retains a reduced red algal nucleus. We searched the organelle and nuclear
      genomes of the cryptophyte Guillardia theta and the diatoms Phaeodactylum
      tricornutum and Thalassiosira pseudonana for aaRS genes and found an insufficient
      number of genes to provide each compartment with a complete set of aaRSs. We
      therefore inferred, with support from localization predictions, that many aaRSs
      are dual targeted. We tested four of the predicted dual targeted aaRSs with green
      fluorescent protein fusion localizations in P. tricornutum and found evidence for
      dual targeting to the mitochondrion and plastid in P. tricornutum and G. theta,
      and indications for dual targeting to the PPC and cytosol in G. theta. This is
      the first report of dual targeting in diatoms or cryptophytes. 

PMID- 25994932
TI  - Evolution of the Translocation and Assembly Module (TAM).
AB  - Bacterial outer membrane proteins require the beta-barrel assembly machinery
      (BAM) for their correct folding and function. The central component of this
      machinery is BamA, an Omp85 protein that is essential and found in all Gram
      negative bacteria. An additional feature of the BAM is the translocation and
      assembly module (TAM), comprised TamA (an Omp85 family protein) and TamB. We
      report that TamA and a closely related protein TamL are confined almost
      exclusively to Proteobacteria and Bacteroidetes/Chlorobi respectively, whereas
      TamB is widely distributed across the majority of Gram-negative bacterial
      lineages. A comprehensive phylogenetic and secondary structure analysis of the
      TamB protein family revealed that TamB was present very early in the evolution of
      bacteria. Several sequence characteristics were discovered to define the TamB
      protein family: A signal-anchor linkage to the inner membrane, beta-helical
      structure, conserved domain architecture and a C-terminal region that mimics
      outer membrane protein beta-strands. Taken together, the structural and
      phylogenetic analyses suggest that the TAM likely evolved from an original
      combination of BamA and TamB, with a later gene duplication event of BamA, giving
      rise to an additional Omp85 sequence that evolved to be TamA in Proteobacteria
      and TamL in Bacteroidetes/Chlorobi. 

PMID- 25994934
TI  - Natural and experimental evolution of sexual conflict within Caenorhabditis
      nematodes.
AB  - BACKGROUND: Although males and females need one another in order to reproduce,
      they often have different reproductive interests, which can lead to conflict
      between the sexes. The intensity and frequency of male-male competition for
      fertilization opportunities is thought to be an important contributor to this
      conflict. The nematode genus Caenorhabditis provides an opportunity to test this
      hypothesis because the frequency of males varies widely among species with
      different mating systems. RESULTS: We find evidence that there is strong inter-
      and intra-sexual conflict within C. remanei, a dioecious species composed of
      equal frequencies of males and females. In particular, some C. remanei males
      greatly reduce female lifespan following mating, and their sperm have a strong
      competitive advantage over the sperm of other males. In contrast, our results
      suggest that both types of conflict have been greatly reduced within C. elegans,
      which is an androdioecious species that is composed of self-fertilizing
      hermaphrodites and rare males. Using experimental evolution in mutant C. elegans
      populations in which sperm production is blocked in hermaphrodites (effectively
      converting them to females), we find that the consequences of sexual conflict
      observed within C. remanei evolve rapidly within C. elegans populations
      experiencing high levels of male-male competition. CONCLUSIONS: Together, these
      complementary data sets support the hypothesis that the intensity of intersexual
      conflict varies with the intensity of competition among males, and that male
      induced collateral damage to mates can evolve very rapidly within populations.

PMID- 25994936
TI  - Short-term donor site morbidity: A comparison of the anterolateral thigh and
      radial forearm fasciocutaneous free flaps.
AB  - BACKGROUND: Donor site morbidity is an important consideration in the overall
      decision-making algorithm for fasciocutaneous free flap reconstruction of the
      head and neck. METHODS: A retrospective case series was conducted of donor site
      complications occurring within 30 days of surgery among 226 consecutive
      anterolateral thigh (ALT) or radial forearm free flap (RFFF) microvascular free
      tissue transfers performed by multiple reconstructive surgeons between 2005 and
      2010. RESULTS: A greater number of donor site complications occurred among
      patients undergoing RFFF versus ALT free flaps (40; 35.4%; vs 14; 12.4%; p <
      .001). Wound dehiscence occurred significantly more frequently among patients
      undergoing RFFF versus ALT free flap reconstruction (34; 30%; vs 6; 5%; p <
      .001). Tendon exposure occurred in 16 of the 113 RFFFs (14.1%). Seromas occurred
      more commonly in the ALT group (6; 5%; vs 2; 1.7%; p = .280). CONCLUSION:
      Although short-term donor site morbidity was low in both groups, the ALT was
      associated with a significantly lower incidence of wound dehiscence with or
      without tendon exposure. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E945
      E948, 2016.

PMID- 25994935
TI  - A comparative study of mechanical strain, icariin and combination stimulations on
      improving osteoinductive potential via NF-kappaB activation in osteoblast-like
      cells.
AB  - BACKGROUND: The combination of drugs and exercise was the effective treatment in
      bone injure and rebuilding in clinic. As mechanical strain has potential in
      inducing the differentiation of osteoblasts in our previous study, the further
      research to investigate the combination of mechanical strain and icariin
      stimulation on inducing osteoblast proliferation, differentiation and the
      possible mechanism in MC3T3-E1 cell line. METHODS: A whole cell enzyme-linked
      immunosorbent assay that detects the bromodeoxyuridine incorporation during DNA
      synthesis was applied to evaluate the proliferation. The mRNA expression of
      alkaline phosphatase (ALP), osteocalcin (OCN), type I collagen (Col I), bone
      morphogenetic protein-2 (BMP-2) and BMP-4 was detected by real-time reverse
      transcription polymerase chain reaction. The activity of ALP was analyzed by
      ELISA and the protein expression of OCN, Col I and BMP-2 was assessed by western
      blot. Moreover, the activity of nuclear transcription factor kappa-B (NF-kappaB)
      signaling pathway was investigated with the expression of inhibitor of kappaB
      (IkappaB) alpha, phosphorylation of IkappaB-alpha (P-IkappaB-alpha), p65, P-p65
      by western blot. RESULTS: We observed that compared to single mechanical strain
      or icariin stimulation, the mRNA and protein expressions of ALP (P < 0.05 or P <
      0.01), OCN (P < 0.01) and Col I (P < 0.05 or P < 0.01) were increased
      significantly by the combination of mechanical strain and icariin stimulation.
      Moreover, the combination of mechanical strain and icariin stimulation could up
      regulate the expression of BMP-2 (P < 0.01) and BMP-4 compared to single
      mechanical strain or icariin stimulation. The combination of mechanical strain
      and icariin stimulation could activate NF-kappaB signaling pathway by increasing
      the expression of IkappaB alpha, P-IkappaB-alpha, p65, P-p65 (P < 0.01).
      CONCLUSION: The combination of mechanical strain and icariin stimulation could
      activate the NF-kappaB pathway to improve the proliferation, differentiation of
      osteoblast-like cells.

PMID- 25994937
TI  - CTA collateral score predicts infarct volume and clinical outcome after
      endovascular therapy for acute ischemic stroke: a retrospective chart review.
AB  - BACKGROUND: Acute ischemic stroke (AIS) due to emergent large-vessel occlusion
      (ELVO) has a poor prognosis. OBJECTIVE: To examine the hypothesis that a better
      collateral score on pretreatment CT angiography (CTA) would correlate with a
      smaller final infarct volume and a more favorable clinical outcome after
      endovascular therapy (EVT). METHODS: A retrospective chart review of the
      University of Tennessee AIS database from February 2011 to February 2013 was
      conducted. All patients with CTA-proven LVO treated with EVT were included.
      Recanalization after EVT was defined by Thrombolysis in Cerebral Infarction
      (TICI) score >=2. Favorable outcome was assessed as a modified Rankin Score <=3.
      RESULTS: Fifty patients with ELVO were studied. The mean National Institutes of
      Health Stroke Scale score was 17 (2-27) and 38 of the patients (76%) received
      intravenous tissue plasminogen activator. The recanalization rate for EVT was
      86.6%. Good clinical outcome was achieved in 32% of patients. Univariate
      predictors of good outcome included good collateral scores (CS) on presenting CTA
      (p=0.043) and successful recanalization (p=0.02). Multivariate analysis confirmed
      both good CS (p=0.024) and successful recanalization (p=0.009) as predictors of
      favorable outcome. Applying results of the multivariate analysis to our cohort we
      were able to determine the likelihood of good clinical outcome as well as
      predictors of smaller final infarct volume after successful recanalization.
      CONCLUSIONS: Good CS predict smaller infarct volumes and better clinical outcome
      in patients recanalized with EVT. These data support the use of this technique in
      selecting patients for EVT. Poor CS should be considered as an exclusion
      criterion for EVT as patients with poor CS have poor clinical outcomes despite
      recanalization.

PMID- 25994938
TI  - Preliminary experience with the liquid embolic material agent PHIL (Precipitating
      Hydrophobic Injectable Liquid) in treating cranial and spinal dural arteriovenous
      fistulas: technical note.
AB  - BACKGROUND: Liquid embolic agents are the preferred embolic material in
      endovascular treatment of pial and brain arteriovenous malformations and dural
      arteriovenous fistulas (DAVFs). There is little choice available in
      interventional neuroradiology practice other than two of the most commonly used
      liquid embolic agents-n-butyl cyanoacrylate and the Onyx liquid embolic system
      (ev3 Neurovascular, Irvine, California, USA). PHIL (Precipitating Hydrophobic
      Injectable Liquid) (Microvention, Inc California, USA) is a new liquid embolic
      agent, CE marked and available for clinical use in Europe. OBJECTIVE: To present
      our preliminary experience using PHIL in treating cranial and spinal DAVFs.
      METHODS: Between September 2014 and January 2015, eight patients, with five
      cranial DAVFs and three spinal DAVFs were treated with PHIL as the sole embolic
      agent used with intent to cure. Clinical presentation, location of DAVF, Borden
      type, fluoroscopic time, radiation dose, procedural time, injecting microcatheter
      used, volume of PHIL injected, complications, immediate angiographic data,
      premorbid and discharge modified Rankin Scale score, and any neurologic deficits
      were included in the analysis. RESULTS: Seven patients were successfully treated
      with complete angiographic exclusion of the fistula in a single sitting.
      Treatment failed in one patient where only suboptimal microcatheter positioning
      could be achieved and PHIL failed to penetrate the fistula's nidus. Venous
      penetration was achieved in all other patients except one with a small fistula,
      but with adequate fistula penetration by the embolic material. No other technical
      complication or neurologic deterioration occurred in any of the patients.
      CONCLUSIONS: PHIL liquid embolic agent appears to be an excellent alternative
      embolic material with certain advantages compared with other available liquid
      embolic agents. Further studies are required to fully evaluate its safety and
      efficacy.

PMID- 25994940
TI  - Analysis of endovascular treatment of ruptured microaneurysms compared with
      ruptured larger aneurysms.
AB  - OBJECTIVE: To retrospectively analyze the complications and outcome of the
      endovascular treatment of ruptured microaneurysms compared with the treatment of
      ruptured larger aneurysms. METHODS: 40 ruptured cerebral microaneurysms treated
      by endovascular techniques were selected retrospectively and compared with 207
      larger ruptured cerebral aneurysms treated by endovascular techniques during the
      same time period. Medical charts and imaging studies were reviewed to analyze
      baseline clinical and epidemiologic characteristics, procedural complications,
      and clinical outcomes RESULTS: Cerebral microaneurysms had a higher incidence of
      intraoperative technical ruptures (13.5% vs 2.9%, p<0.005). The number of
      thromboembolic complications was not increased. Patient prognosis was similar for
      the two groups (mean modified Rankin Scale score 1.81 vs 2.09, p>0.1).
      CONCLUSIONS: Coiling of cerebral microaneurysms has a reasonable safety profile
      with good clinical outcomes, similar to coiling of larger aneurysms. In our
      experience, the systematic use of remodeling balloons, operator experience, and
      the ability to manage complications are the reasons for the satisfactory results.

PMID- 25994939
TI  - Mechanical thrombectomy for acute ischemic stroke with cerebral microbleeds.
AB  - BACKGROUND: The influence of cerebral microbleeds (CMBs) on post-thrombolytic
      hemorrhagic transformation (HT) in patients with acute ischemic stroke remains
      controversial. OBJECTIVE: To investigate the association of CMBs with HT and
      clinical outcomes among patients with large-vessel occlusion strokes treated with
      mechanical thrombectomy. METHODS: We analyzed patients with acute stroke treated
      with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were
      identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the
      association of the presence, burden, and distribution of CMBs with HT, procedural
      complications, in-hospital mortality, and clinical outcome. RESULTS: CMBs were
      detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were
      identified. Fourteen patients (6.8%) had >=2 CMBs, only 1 patient had >=5 CMBs.
      Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients,
      strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There
      were no significant differences between patients with CMBs and those without CMBs
      in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs
      19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital
      mortality (16.2% vs 18.3%), and modified Rankin Scale score 0-3 at discharge.
      CMBs were not independently associated with HT or in-hospital mortality in
      patients treated with either thrombectomy or intravenous thrombolysis followed by
      thrombectomy. CONCLUSIONS: Patients with CMBs are not at increased risk for HT
      and mortality following mechanical thrombectomy for acute stroke. Excluding such
      patients from mechanical thrombectomy is unwarranted. The risk of HT in patients
      with >=5 CMBs requires further study.

PMID- 25994941
TI  - Evaluation of the JRecan device for thrombus retrieval: efficacy and safety in a
      swine model of acute arterial occlusion.
AB  - OBJECTIVE: To evaluate the recanalization efficacy and safety of a novel stent
      retriever in a swine model of acute arterial occlusion. METHODS: The JRecan
      thrombectomy device, a stent retriever with a weaving stent design, was evaluated
      in 18 occluded cervicocerebral vessels of swine. The flow restoration effect
      immediately upon deployment, the reperfusion rate after retrieval, thromboembolic
      events, and complications were assessed. The histologic structure of the renal
      arteries after retriever passage was measured to further assess the safety of
      JRecan. RESULTS: Immediate flow restoration was achieved in 66.7% of occlusions
      (12/18). The reperfusion rate was 94.4% (two Thrombolysis in Cerebral Infarction
      (TICI) 2b and 15 TICI 3). Distal thromboembolic events did not occur. Microscopic
      examination of the arteries after retrieval showed mild degrees of endothelial
      loss in 96.6% (29/30), fibrin or platelet deposition in 53.3% (16/30), and
      disruption of the internal elastic lamina in 10% (3/30), without severe
      pathologic lesions. CONCLUSIONS: The JRecan is highly effective at clot removal
      with a favorable safety profile and merits further development as a stent
      retriever for the treatment of acute ischemic stroke.

PMID- 25994942
TI  - Reversible transverse sinus collapse in a patient with idiopathic intracranial
      hypertension.
AB  - The association of idiopathic intracranial hypertension (IIH) with stenosis or
      narrowing of the transverse sinuses (TSs) is well known. However, there is debate
      as to whether the stenosis is a cause or consequence. Here we describe a case of
      IIH and narrowing of the TSs, with four relapses and recoveries after repeated
      CSF diversions with lumbar puncture (LP) over 2 months. Subsequently,
      implantation of a lumboperitoneal shunt (LPrS) ensured recovery. MR venography 20
      months after LPrS showed normally calibrated TSs. We show repeated MR venography
      findings before and after the LPs, and discuss the pathogenesis of IIH in terms
      of the cause and effect relationship between IIH and sinus collapse. 

PMID- 25994933
TI  - Adaptation to Low Salinity Promotes Genomic Divergence in Atlantic Cod (Gadus
      morhua L.).
AB  - How genomic selection enables species to adapt to divergent environments is a
      fundamental question in ecology and evolution. We investigated the genomic
      signatures of local adaptation in Atlantic cod (Gadus morhua L.) along a natural
      salinity gradient, ranging from 350/00 in the North Sea to 70/00 within the
      Baltic Sea. By utilizing a 12 K SNPchip, we simultaneously assessed neutral and
      adaptive genetic divergence across the Atlantic cod genome. Combining outlier
      analyses with a landscape genomic approach, we identified a set of directionally
      selected loci that are strongly correlated with habitat differences in salinity,
      oxygen, and temperature. Our results show that discrete regions within the
      Atlantic cod genome are subject to directional selection and associated with
      adaptation to the local environmental conditions in the Baltic- and the North
      Sea, indicating divergence hitchhiking and the presence of genomic islands of
      divergence. We report a suite of outlier single nucleotide polymorphisms within
      or closely located to genes associated with osmoregulation, as well as genes
      known to play important roles in the hydration and development of oocytes. These
      genes are likely to have key functions within a general osmoregulatory framework
      and are important for the survival of eggs and larvae, contributing to the
      buildup of reproductive isolation between the low-salinity adapted Baltic cod and
      the adjacent cod populations. Hence, our data suggest that adaptive responses to
      the environmental conditions in the Baltic Sea may contribute to a strong and
      effective reproductive barrier, and that Baltic cod can be viewed as an example
      of ongoing speciation. 

PMID- 25994943
TI  - Importance of repeat angiography in the diagnosis of iatrogenic anterior cerebral
      artery territory pseudoaneurysm following endoscopic sinus surgery.
AB  - Iatrogenic intracranial pseudoaneurysm formation and rupture are rare
      complications following endoscopic sinus surgery. Given the propensity for
      devastating neurologic injury after a relatively routine procedure, swift
      diagnosis and treatment is essential. The authors present a patient who
      experienced bifrontal intracranial hemorrhage and subarachnoid hemorrhage due to
      a ruptured iatrogenic frontopolar artery pseudoaneurysm caused during routine
      endoscopic sinus surgery. The pseudoaneurysm was not present on initial
      angiograms but became apparent radiographically 19 days after the endoscopic
      procedure. Endovascular treatment consisted of coil and Onyx embolization for
      sacrifice of the parent vessel proximal to the lesion. Early recognition of
      iatrogenic intracranial vascular injury is important to allow for rapid
      treatment. Initial radiographic studies may be unreliable in excluding the
      presence of a pseudoaneurysm so delayed repeat angiographic assessment is
      necessary, particularly in the presence of a high index of clinical suspicion.
      Endovascular techniques may provide an effective and safe option for the
      treatment of iatrogenic anterior cerebral artery distribution pseudoaneurysms. 

PMID- 25994944
TI  - Photocatalytic metal-organic frameworks for the aerobic oxidation of arylboronic
      acids.
AB  - A photocatalytic Ru complex was incorporated into a Zr(iv)-based metal-organic
      framework (MOF) via postsynthetic methods. The resulting UiO-67-Ru(bpy)3 shows
      efficient and recyclable catalytic activity for the aerobic oxidation of
      arylboronic acids under near-UV and visible light irradiation. 

PMID- 25994945
TI  - Occlusal dysesthesia: a topical narrative review.
AB  - Occlusal dysesthesia (OD) is a disorder characterised by the sensation of
      uncomfortable bite with no obvious occlusal discrepancy. It is usually associated
      with emotional distress and is elicited by dental occlusal procedures. Multiple
      dental treatments are often provided to try to resolve the symptoms, but the
      outcome is usually dissatisfying for the dentist and disappointing for the
      patient. To summarise the specific features of OD, a PubMed search was carried
      out looking for all papers related to the topic. The references from the studies
      selected and from review articles were also examined for further relevant papers.
      A total of 138 articles were first identified, of which 18 of them were
      considered relevant to the topic. This article reviews the epidemiology, taxonomy
      and etio-pathophysiology, symptomatology, diagnosis and treatment of OD, with
      special relevance to issues of clinical importance and dental therapy. Any dental
      treatment must be avoided in patients with OD, because the results could be
      inadequate and it usually worsens the symptoms. 

PMID- 25994947
TI  - Broadening the definition of autoinflammation.
AB  - Initially, the concept of autoinflammation posited that there be no involvement
      of autoreactive B or T cells, and no evidence of infection. These criteria served
      well to help establish the concept, and distinguish autoinflammatory diseases
      from autoimmune or infectious conditions. However, the characterisation of
      additional monogenic autoinflammatory diseases has established that a primary
      trigger of the innate immune system may also be accompanied by infection or
      manifestations of autoimmunity, which may even contribute to pathogenesis. This
      issue of Seminars in Immunopathology draws out these themes and also shows how
      autoinflammation can help to maintain homeostasis, which is its primary
      evolutionary function. Elucidating the fundamental innate immune pathways
      underlying autoinflammatory disease leads back to these same homeostatic
      parameters, to inform about how infection is sensed, and providing for new
      targets against chronic inflammatory disease. 

PMID- 25994948
TI  - A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's
      syndrome.
AB  - OBJECTIVE: Our aim was to review short- and long-term outcomes of patients
      treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome.
      METHODS: We reviewed the literature and analysed our experience with 53 patients
      treated with BADx since 1990 in our institution. RESULTS: BADx is considered if
      ACTH-dependent Cushing's syndrome is refractory to other treatment modalities. In
      Cushing's disease (CD), BADx is mainly used as an ultima ratio after
      transsphenoidal surgery and medical therapies have failed. In these cases, the
      time span between the first diagnosis of CD and treatment with BADx is relatively
      long (median 44 months). In ectopic Cushing's syndrome, the time from diagnosis
      to BADx is shorter (median 2 months), and BADx is often performed as an emergency
      procedure because of life-threatening complications of severe hypercortisolism.
      In both situations, BADx is relatively safe (median surgical morbidity 15%;
      median surgical mortality 3%) and provides excellent control of hypercortisolism;
      Cushing's-associated signs and symptoms are rapidly corrected, and co-morbidities
      are stabilised. In CD, the quality of life following BADx is rapidly improving,
      and long-term mortality is low. Specific long-term complications include the
      development of adrenal crisis and Nelson's syndrome. In ectopic Cushing's
      syndrome, long-term mortality is high but is mostly dependent on the prognosis of
      the underlying malignant neuroendocrine tumour. CONCLUSION: BADx is a relatively
      safe and highly effective treatment, and it provides adequate control of long
      term co-morbidities associated with hypercortisolism.

PMID- 25994946
TI  - Protein misfolding and dysregulated protein homeostasis in autoinflammatory
      diseases and beyond.
AB  - Cells have a number of mechanisms to maintain protein homeostasis, including
      proteasome-mediated degradation of ubiquitinated proteins and autophagy, a
      regulated process of "self-eating" where the contents of entire organelles can be
      recycled for other uses. The unfolded protein response prevents protein overload
      in the secretory pathway. In the past decade, it has become clear that these
      fundamental cellular processes also help contain inflammation though degrading
      pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling
      pathways such as the UPR can also be co-opted by toll-like receptor and
      mitochondrial reactive oxygen species signaling to induce inflammatory responses.
      Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can
      overcome normal protein homeostasis mechanisms, resulting in autoinflammatory
      diseases. Conversely, Mendelian defects in the proteasome cause protein
      accumulation, which can trigger interferon-dependent autoinflammatory disease. In
      non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or
      autophagy pathways can contribute to disease, and in diseases not formerly
      considered inflammatory such as neurodegenerative conditions and type 2 diabetes,
      there is increasing evidence that cell intrinsic or environmental alterations in
      protein homeostasis may contribute to pathogenesis. 

PMID- 25994949
TI  - Median-lower normal levels of serum thyroxine are associated with low
      triiodothyronine levels and body temperature in patients with central
      hypothyroidism.
AB  - OBJECTIVE: Although it has been recommended that serum free thyroxine (FT4)
      levels should be targeted to middle-upper normal levels during levothyroxine (l
      T4) replacement therapy in patients with central hypothyroidism (CeH), the
      rationale has not been clarified. METHODS: A retrospective single-center study
      enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx),
      n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C),
      n=29). The patients had received L-T4 therapy at the Kobe University Hospital
      between 2003 and 2013. They were stratified according to serum FT4 level (>= 1.10
      or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3)
      levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH
      replacement therapy on thyroid function was also analyzed. RESULTS: FT3 levels
      and FT3/FT4 ratios were significantly lower in patients with CeH than in patients
      with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was
      significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in
      patients with PH, whereas no differences were found in patients with FT4 >= 1.10
      ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement
      therapy (P=0.018). CONCLUSION: In CeH, patients with median-lower normal levels
      of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support
      the target levels of serum FT4 as middle-upper normal levels during l-T4
      replacement therapy in patients with CeH.

PMID- 25994951
TI  - Staging of development in Terrien's degeneration based on corneal curvatures
      detected by optical coherence tomography.
AB  - PURPOSE: We aimed to explore a new classification system based on the change of
      focal corneal curvatures and corneal thickness in Terrien's corneal degeneration
      with optical coherence tomography. METHODS: This was a cross-sectional study.
      Ninety eyes of 59 patients with Terrien's degeneration were examined with slit
      lamp biomicroscopy, Orbscan II corneal tomography and the Visante OCT system, and
      were staged according to Suveges's classification. RESULTS: The ratio of female
      to male patients was 1.57:1. The ratio of bilateral to unilateral lesions was
      1.27:1. The occurrence of bilateral lesion was higher in males than in females
      (x(2) = 7.791, p = 0.005). There was no difference in the mean age between female
      and male patients (t = 1.859, p = 0.068), or between patients with bilateral and
      unilateral lesions (t = 1.797, p = 0.078).The minimum corneal thickness at the
      thinnest point (MinCT) and anterior curvature of the peripheral cornea were
      almost normal in the initial stages of disease. The anterior curvature was
      flattened when MinCT became less than 0.56 mm, returned to normal when MinCT was
      no more than 0.24 mm, and bowed forward when MinCT was no more than 0.13 mm. The
      posterior corneal curvatures were bowed forward from their normal curvatures in
      42 of 90 eyes when MinCT was no more than 0.41 mm. These eyes' MinCT ranged from
      0 to 0.41 mm. There was a strong correlation between change of corneal curvatures
      and MinCT (r = -0.943, p < 0.01). A new classification of six stages based on
      corneal curvatures is proposed for evaluating the development of Terrien's
      degeneration. Statistically, there was a moderate correlation between either the
      Suveges staging or the new staging and the width and circumference of corneal
      lesions, visual acuity, and simulated keratometric value (all r < 0.6). The
      correlation of MinCT with the new classification based on corneal curvatures was
      higher than that with Suveges's classification (r 1 vs. r 2 , -0.943 vs. -0.801).
      CONCLUSION: The proposed new classification based on focal corneal curvatures is
      closely associated with corneal thinning, is valuable for evaluating the
      development of Terrien's degeneration and may enhance surgical planning.

PMID- 25994950
TI  - Open Source Bayesian Models. 1. Application to ADME/Tox and Drug Discovery
      Datasets.
AB  - On the order of hundreds of absorption, distribution, metabolism, excretion, and
      toxicity (ADME/Tox) models have been described in the literature in the past
      decade which are more often than not inaccessible to anyone but their authors.
      Public accessibility is also an issue with computational models for bioactivity,
      and the ability to share such models still remains a major challenge limiting
      drug discovery. We describe the creation of a reference implementation of a
      Bayesian model-building software module, which we have released as an open source
      component that is now included in the Chemistry Development Kit (CDK) project, as
      well as implemented in the CDD Vault and in several mobile apps. We use this
      implementation to build an array of Bayesian models for ADME/Tox, in vitro and in
      vivo bioactivity, and other physicochemical properties. We show that these models
      possess cross-validation receiver operator curve values comparable to those
      generated previously in prior publications using alternative tools. We have now
      described how the implementation of Bayesian models with FCFP6 descriptors
      generated in the CDD Vault enables the rapid production of robust machine
      learning models from public data or the user's own datasets. The current study
      sets the stage for generating models in proprietary software (such as CDD) and
      exporting these models in a format that could be run in open source software
      using CDK components. This work also demonstrates that we can enable
      biocomputation across distributed private or public datasets to enhance drug
      discovery. 

PMID- 25994953
TI  - Arterial baroreceptor reflex control of renal sympathetic nerve activity
      following chronic myocardial infarction in male, female, and ovariectomized
      female rats.
AB  - There is controversy regarding whether the arterial baroreflex control of renal
      sympathetic nerve activity (SNA) in heart failure is altered. We investigated the
      impact of sex and ovarian hormones on changes in the arterial baroreflex control
      of renal SNA following a chronic myocardial infarction (MI). Renal SNA and
      arterial pressure were recorded in chloralose-urethane anesthetized male, female,
      and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery.
      Animals were grouped according to MI size (sham, small and large MI). Ovary
      intact females had a lower mortality rate post-MI (24%) compared with both males
      (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI,
      displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As
      a result, the male large MI group (49 +/- 6 vs. 84 +/- 5% in male sham group) and
      OVX large MI group (37 +/- 3 vs. 75 +/- 5% in OVX sham group) displayed
      significantly reduced arterial baroreflex range of control of normalized renal
      SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of
      normalized renal SNA was unchanged regardless of MI size. In males and OVX there
      was a significant, positive correlation between left ventricle (LV) ejection
      fraction and arterial baroreflex range of control of normalized renal SNA, but
      not absolute renal SNA, that was not evident in ovary-intact females. The current
      findings demonstrate that the arterial baroreflex control of renal SNA post-MI is
      preserved in ovary-intact females, and the state of left ventricular dysfunction
      significantly impacts on the changes in the arterial baroreflex post-MI.

PMID- 25994954
TI  - Differences in temporal aspects of food acquisition between rats and two strains
      of mice in a closed operant economy.
AB  - Rats and mice were studied for changes in meal-taking structure in a closed
      operant food economy, in which the consummatory or unit prices for food were
      increased. In experiment 1, as food price increased, male rats modestly decreased
      the number of meals per day and increased mean meal size. Female rats were
      similar to males but had smaller meal size and, at low costs, took more meals per
      day. In experiment 2, male and female B6 mice reduced food intake as price
      increased, accompanied by decreased meal number without change in meal size. They
      showed grazing-like behavior in the first part of the night. In contrast, we
      report in experiment 3, a large increase in intake and meal size during the final
      trimester of pregnancy. In experiment 4, we report that CD1 male mice subjected
      to a unit price series performed comparably to rats, and not like B6 mice. Other
      CD1 mice were tested using an interval schedule, and we found that mice were able
      to adapt eating patterns to greatly increased time demands without compromising
      total intake. Data are discussed in terms of the intercalation of food
      acquisition with global patterns of activity. Such interactions of organism and
      food environment are in particular need of mechanistic investigation.

PMID- 25994952
TI  - Minimal residual disease in acute myeloid leukemia--current status and future
      perspectives.
AB  - In acute myeloid leukemia (AML), the achievement of a morphological complete
      remission (CR) is an important milestone on the road to cure. Still, the majority
      of patients who achieve a morphological CR will eventually relapse. Thus,
      morphological means are not sensitive enough to detect clinically relevant tumor
      burdens left behind after therapy. Over the last years, several methodologies,
      particularly multiparameter flow cytometry and polymerase chain reaction, have
      emerged that can detect, quantify, and monitor submicroscopic amounts of leukemia
      cells ("minimal residual disease", MRD). Newer techniques, such as next
      generation sequencing, have not only changed our understanding of the molecular
      pathogenesis and clonal heterogeneity of AML but may also be used for MRD
      detection. Increasing evidence indicates that MRD could play an important role in
      dynamically refining disease risk and, perhaps, serve to fine-tune post-remission
      therapy in a risk-adapted manner, although the latter concept awaits validation
      through well-controlled trials. In this review, we discuss the current use of MRD
      measurements during AML treatment and highlight future perspectives. 

PMID- 25994955
TI  - Endothelium-derived ET-1 and the development of renal injury.
AB  - The role of the vasoactive peptide endothelin-1 (ET-1) in renal injury is not
      fully understood. In this review, we examine the genetic models available to
      understand the autocrine/paracrine mechanisms by which ET-1 leads to renal injury
      and propose the working hypothesis that endothelium-derived ET-1 induces renal
      injury by initiating renal tubular apoptosis in a paracrine manner. 

PMID- 25994956
TI  - High-dose ascorbate with low-dose amphotericin B attenuates severity of disease
      in a model of the reappearance of candidemia during sepsis in the mouse.
AB  - Amphotericin B (Ampho B) isa fungicidal drug that causes cell wall injury.
      Pharmacological ascorbate induces the extracellular prooxidants, which might
      enter the Ampho B-induced cell wall porosity and act synergistically.W e tested
      low-dose Ampho B with a short course of pharmacological ascorbate using a mouse
      model of sepsis preconditioned with an injection of Candida albicans 6 h prior to
      cecal ligation and puncture (CLP). In this model, candidemia reappeared as early
      as 6 h after CLP with a predictably high mortality rate. This characteristic
      mimics sepsis in the phase of immunosuppression inpatients. Using the model, at
      12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological
      ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle
      controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate
      was 53%, compared with < 11% for low-dose Ampho B or high-dose Ampho B alone. In
      addition, a beneficial effect was demonstrated in terms of kidney damage,liver
      injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury
      was less severe in low-dose Ampho B plus ascorbate combination therapy due to
      less severe sepsis. Moreover, ascorbate enhanced the effectiveness of
      phagocytosis against C. albicans in human phagocytic cells. Taken together, the
      data indicate that the new mouse model simulates sepsis-induced immunosuppression
      and that the combination of pharmacological ascorbate with an antifungal drug is
      a potentially effective treatment that may reduce nephrotoxicity, and perhaps
      also increase fungicidal activity in patients with systemic candidiasis caused by
      Candida albicans.

PMID- 25994958
TI  - Edzard Ernst: Guiltiest pleasure is research.

PMID- 25994957
TI  - Angiotensin II regulates brain (pro)renin receptor expression through activation
      of cAMP response element-binding protein.
AB  - We reported that brain (pro)renin receptor (PRR) expression levels are elevated
      in DOCA-salt-induced hypertension; however, the underlying mechanism remained
      unknown. To address whether ANG II type 1 receptor (AT1R) signaling is involved
      in this regulation, we implanted a DOCA pellet and supplied 0.9% saline as the
      drinking solution to C57BL/6J mice. Sham pellet-implanted mice that were provided
      regular drinking water served as controls. Concurrently, mice were
      intracerebroventricularly infused with the AT1R blocker losartan, angiotensin
      converting-enzyme inhibitor captopril, or artificial cerebrospinal fluid for 3
      wk. Intracerebroventricular infusion of losartan or captopril attenuated DOCA
      salt-induced PRR mRNA elevation in the paraventricular nucleus of the
      hypothalamus, suggesting a role for ANG II/AT1R signaling in regulating PRR
      expression during DOCA-salt hypertension. To test which ANG II/AT1R downstream
      transcription factors were involved in PRR regulation, we treated Neuro-2A cells
      with ANG II with or without CREB (cAMP response element-binding protein) or AP-1
      (activator protein-1) inhibitors, or CREB siRNA. CREB and AP-1 inhibitors, as
      well as CREB knockdown abolished ANG II-induced increases in PRR levels. ANG II
      also induced PRR upregulation in primary cultured neurons. Chromatin
      immunoprecipitation assays revealed that ANG II treatment increased CREB binding
      to the endogenous PRR promoter in both cultured neurons and hypothalamic tissues
      of DOCA-salt hypertensive mice. This increase in CREB activity was reversed by
      AT1R blockade. Collectively, these findings indicate that ANG II acts via AT1R to
      upregulate PRR expression both in cultured cells and in DOCA-salt hypertensive
      mice by increasing CREB binding to the PRR promoter. 

PMID- 25994959
TI  - Modulation of Beta-Band Activity in the Subgenual Anterior Cingulate Cortex
      during Emotional Empathy in Treatment-Resistant Depression.
AB  - Deep brain stimulation (DBS) is a promising approach in treatment-resistant
      depression (TRD). TRD is associated with problems in interpersonal relationships,
      which might be linked to impaired empathy. Here, we investigate the influence of
      DBS in the subgenual anterior cingulate cortex (sgACC) on empathy in patients
      with TRD and explore the pattern of oscillatory sgACC activity during performance
      of the multifaceted empathy test. We recorded local field potential activity
      directly from sgACC via DBS electrodes in patients. Based on previous behavioral
      findings, we expected disrupted empathy networks. Patients showed increased
      empathic involvement ratings toward negative stimuli as compared with healthy
      subjects that were significantly reduced after 6 months of DBS. Stimulus-related
      oscillatory activity pattern revealed a broad desynchronization in the beta (14
      35 Hz) band that was significantly larger during patients' reported emotional
      empathy for negative stimuli than when patients reported to have no empathy. Beta
      desynchronization for empathic involvement correlated with self-reported severity
      of depression. Our results indicate a "negativity bias" in patients that can be
      reduced by DBS. Moreover, direct recordings show activation of the sgACC area
      during emotional processing and propose that changes in beta-band oscillatory
      activity in the sgACC might index empathic involvement of negative emotion in
      TRD.

PMID- 25994960
TI  - Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal
      Investigation of Structural and Functional Connectivity.
AB  - Episodic memories are established and maintained by close interplay between
      hippocampus and other cortical regions, but degradation of a fronto-striatal
      network has been suggested to be a driving force of memory decline in aging. We
      wanted to directly address how changes in hippocampal-cortical versus striatal
      cortical networks over time impact episodic memory with age. We followed 119
      healthy participants (20-83 years) for 3.5 years with repeated tests of episodic
      verbal memory and magnetic resonance imaging for quantification of functional and
      structural connectivity and regional brain atrophy. While hippocampal-cortical
      functional connectivity predicted memory change in young, changes in cortico
      striatal functional connectivity were related to change in recall in older
      adults. Within each age group, effects of functional and structural connectivity
      were anatomically closely aligned. Interestingly, the relationship between
      functional connectivity and memory was strongest in the age ranges where the rate
      of reduction of the relevant brain structure was lowest, implying selective
      impacts of the different brain events on memory. Together, these findings suggest
      a partly sequential and partly simultaneous model of brain events underlying
      cognitive changes in aging, where different functional and structural events are
      more or less important in various time windows, dismissing a simple uni-factorial
      view on neurocognitive aging. 

PMID- 25994961
TI  - Individual Differences in Reward and Somatosensory-Motor Brain Regions Correlate
      with Adiposity in Adolescents.
AB  - The prevalence of adolescent obesity has increased dramatically over the past
      three decades, and research has documented that the number of television shows
      viewed during childhood is associated with greater risk for obesity. In
      particular, considerable evidence suggests that exposure to food marketing
      promotes eating habits that contribute to obesity. The present study examines
      neural responses to dynamic food commercials in overweight and healthy-weight
      adolescents using functional magnetic resonance imaging (fMRI). Compared with non
      food commercials, food commercials more strongly engaged regions involved in
      attention and saliency detection (occipital lobe, precuneus, superior temporal
      gyri, and right insula) and in processing rewards [left and right nucleus
      accumbens (NAcc) and left orbitofrontal cortex (OFC)]. Activity in the left OFC
      and right insula further correlated with subjects' percent body fat at the time
      of the scan. Interestingly, this reward-related activity to food commercials was
      accompanied by the additional recruitment of mouth-specific somatosensory-motor
      cortices-a finding that suggests the intriguing possibility that higher-adiposity
      adolescents mentally simulate eating behaviors and offers a potential neural
      mechanism for the formation and reinforcement of unhealthy eating habits that may
      hamper an individual's ability lose weight later in life.

PMID- 25994963
TI  - Thalamic Responses to Nociceptive-Specific Input in Humans: Functional
      Dichotomies and Thalamo-Cortical Connectivity.
AB  - While nociceptive cortical activation is now well characterized in humans,
      understanding of the nociceptive thalamus remains largely fragmentary. We used
      laser stimuli and intracerebral electrodes in 17 human subjects to record
      nociceptive-specific field responses in 4 human thalamic nuclei and a number of
      cortical areas. Three nuclei known to receive spinothalamic (STT) projections in
      primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central
      lateral [CL]) exhibited responses with similar latency, indicating their parallel
      activation by nociceptive afferents. Phase coherence analysis, however, revealed
      major differences in their functional connectivity: while VPL and PuA drove a
      limited set of cortical targets, CL activities were synchronized with a large
      network including temporal, parietal, and frontal areas. Our data suggest that
      STT afferents reach simultaneously a set of lateral and medial thalamic regions
      unconstrained by traditional nuclear borders. The broad pattern of associated
      cortical networks suggests that a single nociceptive volley is able to trigger
      the sensory, cognitive, and emotional activities that underlie the complex pain
      experience. The medial pulvinar, an associative nucleus devoid of STT input,
      exhibited delayed responses suggesting its dependence on descending cortico
      thalamic projections. Its widespread cortical connectivity suggests a role in
      synchronizing parietal, temporal, and frontal activities, hence contributing to
      the access of noxious input to conscious awareness.

PMID- 25994962
TI  - Altered Gray Matter Structural Covariance Networks in Early Stages of Alzheimer's
      Disease.
AB  - Clinical symptoms observed in Alzheimer's disease (AD) patients may reflect
      variations within specific large-scale brain networks, modeling AD as a
      disconnection syndrome. The present magnetic resonance imaging study aims to
      compare the organization of gray matter structural covariance networks between
      109 cognitively unimpaired controls (CTRL) and 109 AD patients positive to beta
      amyloid at the early stages of the disease, using voxel-based morphometry. The
      default-mode network (DMN; medial temporal lobe subsystem) was less extended in
      AD patients in comparison with CTRL, with a significant decrease in the
      structural association between the entorhinal cortex and the medial prefrontal
      and the dorsolateral prefrontal cortices. The DMN (midline core subsystem) was
      also less extended in AD patients. Trends toward increased structural association
      were observed in the salience and executive control networks. The observed
      changes suggest that early disruptions in structural association between
      heteromodal association cortices and the entorhinal cortex could contribute to an
      isolation of the hippocampal formation, potentially giving rise to the clinical
      hallmark of AD, progressive memory impairment. It also provides critical support
      to the hypothesis that the reduced connectivity within the DMN in early AD is
      accompanied by an enhancement of connectivity in the salience and executive
      control networks.

PMID- 25994964
TI  - Exploring the effects of cell seeding density on the differentiation of human
      pluripotent stem cells to brain microvascular endothelial cells.
AB  - BACKGROUND: Brain microvascular-like endothelial cells (BMECs) derived from human
      pluripotent stem cells (hPSCs) have significant promise as tools for drug
      screening and studying the structure and function of the BBB in health and
      disease. The density of hPSCs is a key factor in regulating cell fate and yield
      during differentiation. Prior reports of hPSC differentiation to BMECs have
      seeded hPSCs in aggregates, leading to non-uniform cell densities that may result
      in differentiation heterogeneity. Here we report a singularized-cell seeding
      approach compatible with hPSC-derived BMEC differentiation protocols and evaluate
      the effects of initial hPSC seeding density on the subsequent differentiation,
      yield, and blood-brain barrier (BBB) phenotype. METHODS: A range of densities of
      hPSCs was seeded and differentiated, with the resultant endothelial cell yield
      quantified via VE-cadherin flow cytometry. Barrier phenotype of purified hPSC
      derived BMECs was measured via transendothelial electrical resistance (TEER), and
      purification protocols were subsequently optimized to maximize TEER. Expression
      of characteristic vascular markers, tight junction proteins, and transporters was
      confirmed by immunocytochemistry and quantified by flow cytometry. P-glycoprotein
      and MRP-family transporter activity was assessed by intracellular accumulation
      assay. RESULTS: The initial hPSC seeding density of approximately 30,000
      cells/cm(2) served to maximize the yield of VE-cadherin+ BMECs per input hPSC.
      BMECs displayed the highest TEER (>2,000 Omega * cm(2)) within this same range of
      initial seeding densities, although optimization of the BMEC purification method
      could minimize the seeding density dependence for some lines. Localization and
      expression levels of tight junction proteins as well as efflux transporter
      activity were largely independent of hPSC seeding density. Finally, the utility
      of the singularized-cell seeding approach was demonstrated by scaling the
      differentiation and purification process down from 6-well to 96-well culture
      without impacting BBB phenotype. CONCLUSIONS: Given the yield and barrier
      dependence on initial seeding density, the singularized-cell seeding approach
      reported here should enhance the reproducibility and scalability of hPSC-derived
      BBB models, particularly for the application to new pluripotent stem cell lines.

PMID- 25994965
TI  - Immunization with HSV-2 gB-CCL19 Fusion Constructs Protects Mice against Lethal
      Vaginal Challenge.
AB  - There is a lack of an HSV-2 vaccine, in part as the result of various factors
      that limit robust and long-term memory immune responses at the mucosal portals of
      viral entry. We previously demonstrated that chemokine CCL19 augmented mucosal
      and systemic immune responses to HIV-1 envelope glycoprotein. Whether such
      enhanced immunity can protect animals against virus infection remains to be
      addressed. We hypothesized that using CCL19 in a fusion form to direct an
      immunogen to responsive immunocytes might have an advantage over CCL19 being used
      in combination with an immunogen. We designed two fusion constructs, plasmid
      (p)gBIZCCL19 and pCCL19IZgB, by fusing CCL19 to the C- or N-terminal end of the
      extracellular HSV-2 glycoprotein B (gB) with a linker containing two (Gly4Ser)2
      repeats and a GCN4-based isoleucine zipper motif for self-oligomerization.
      Following immunization in mice, pgBIZCCL19 and pCCL19IZgB induced strong gB
      specific IgG and IgA in sera and vaginal fluids. The enhanced systemic and
      mucosal Abs showed increased neutralizing activity against HSV-2 in vitro.
      Measurement of gB-specific cytokines demonstrated that gB-CCL19 fusion constructs
      induced balanced Th1 and Th2 cellular immune responses. Moreover, mice vaccinated
      with fusion constructs were well protected from intravaginal lethal challenge
      with HSV-2. Compared with pgB and pCCL19 coimmunization, fusion constructs
      increased mucosal surface IgA(+) cells, as well as CCL19-responsive immunocytes
      in spleen and mesenteric lymph nodes. Our findings indicate that enhanced humoral
      and cellular immune responses can be achieved by immunization with an immunogen
      fused to a chemokine, providing information for the design of vaccines against
      mucosal infection by HSV-2 and other sexually transmitted viruses. 

PMID- 25994966
TI  - Bipartite Nuclear Localization Signal Controls Nuclear Import and DNA-Binding
      Activity of IFN Regulatory Factor 3.
AB  - Accurate cellular localization plays a crucial role in the effective function of
      most signaling proteins, and nuclear trafficking is central to the function of
      transcription factors. IFN regulatory factor (IRF)3 is a master transcription
      factor responsible for the induction of type I IFN, which plays a crucial role in
      host antiviral innate immune responses. However, the mechanisms for control and
      regulation of IRF3 nuclear import largely remain to be elucidated. In our study,
      we identified a bipartite nuclear localization signal (NLS) in IRF3, with two
      interdependent basic clusters separated by a 7-aa linker. Our study further
      demonstrated that the bipartite NLS of IRF3 is also critical for IRF3 DNA-binding
      activity, indicating that the two functions of this region are integrated, which
      is in contrast to other IRFs. Furthermore, the IFN bioassay and infection studies
      suggest that IRF3 NLS is essential to the IRF3-mediated IFN responses and
      antiviral immunity. Overall, our results reveal a previously unrecognized
      bipartite NLS for IRF3 that contains both DNA-binding activity and nuclear import
      function, and they shed light on the regulatory mechanisms of IRF3 activation and
      IRF3-mediated antiviral responses. 

PMID- 25994967
TI  - Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host
      Disease.
AB  - Adoptive transfer of freshly isolated natural occurring CD4(+)CD25(+)Foxp3(+)
      regulatory T cells (Treg) prevents graft-versus-host disease (GVHD) in several
      animal models and following hematopoietic cell transplantation (HCT) in clinical
      trials. Donor-derived Treg have been mainly used, as they share the same MHC with
      CD4(+) and CD8(+) conventional T cells (Tcon) that are primarily responsible for
      GVHD. Third party-derived Treg are a promising alternative for cellular therapy,
      as they can be prepared in advance, screened for pathogens and activity, and
      banked. We explored MHC disparities between Treg and Tcon in HCT to evaluate the
      impact of different Treg populations in GVHD prevention and survival. Third-party
      Treg and donor Treg are equally suppressive in ex vivo assays, whereas both donor
      and third-party but not host Treg protect from GVHD in allogeneic HCT, with donor
      Treg being the most effective. In an MHC minor mismatched transplantation model
      (C57BL/6 -> BALB/b), donor and third-party Treg were equally effective in
      controlling GVHD. Furthermore, using an in vivo Treg depletion mouse model, we
      found that Treg exert their main suppressive activity in the first 2 d after
      transplantation. Third-party Treg survive for a shorter period of time after
      adoptive transfer, but despite the shorter survival, they control Tcon
      proliferation in the early phases of HCT. These studies provide relevant insights
      on the mechanisms of Treg-mediated protection from GVHD and support for the use
      of third-party Treg in clinical trials. 

PMID- 25994968
TI  - Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT
      and CD226.
AB  - Regulatory T cells (Tregs) play a central role in counteracting inflammation and
      autoimmunity. A more complete understanding of cellular heterogeneity and the
      potential for lineage plasticity in human Treg subsets may identify markers of
      disease pathogenesis and facilitate the development of optimized cellular
      therapeutics. To better elucidate human Treg subsets, we conducted direct
      transcriptional profiling of CD4(+)FOXP3(+)Helios(+) thymic-derived Tregs and
      CD4(+)FOXP3(+)Helios(-) T cells, followed by comparison with CD4(+)FOXP3(
      )Helios(-) T conventional cells. These analyses revealed that the coinhibitory
      receptor T cell Ig and ITIM domain (TIGIT) was highly expressed on thymic-derived
      Tregs. TIGIT and the costimulatory factor CD226 bind the common ligand CD155.
      Thus, we analyzed the cellular distribution and suppressive activity of isolated
      subsets of CD4(+)CD25(+)CD127(lo/-) T cells expressing CD226 and/or TIGIT. We
      observed TIGIT is highly expressed and upregulated on Tregs after activation and
      in vitro expansion, and is associated with lineage stability and suppressive
      capacity. Conversely, the CD226(+)TIGIT(-) population was associated with reduced
      Treg purity and suppressive capacity after expansion, along with a marked
      increase in IL-10 and effector cytokine production. These studies provide
      additional markers to delineate functionally distinct Treg subsets that may help
      direct cellular therapies and provide important phenotypic markers for assessing
      the role of Tregs in health and disease. 

PMID- 25994969
TI  - Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection.
AB  - Pneumocystis pneumonia remains a common opportunistic infection in the diverse
      immunosuppressed population. One clear risk factor for susceptibility to
      Pneumocystis is a declining CD4(+) T cell count in the setting of HIV/AIDS or
      primary immunodeficiency. Non-HIV-infected individuals taking immunosuppressive
      drug regimens targeting T cell activation are also susceptible. Given the crucial
      role of CD4(+) T cells in host defense against Pneumocystis, we used RNA
      sequencing of whole lung early in infection in wild-type and CD4-depleted animals
      as an unbiased approach to examine mechanisms of fungal clearance. In wild-type
      mice, a strong eosinophil signature was observed at day 14 post Pneumocystis
      challenge, and eosinophils were increased in the bronchoalveolar lavage fluid of
      wild-type mice. Furthermore, eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice
      were more susceptible to Pneumocystis infection when compared with BALB/c
      controls, and bone marrow-derived eosinophils had in vitro Pneumocystis killing
      activity. To drive eosinophilia in vivo, Rag1(-/-) mice were treated with a
      plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic
      injection. The pIL5-treated mice had increased serum IL-5 and eosinophilia in the
      lung, as well as reduced Pneumocystis burden, compared with mice treated with
      control plasmid. In addition, pIL5 treatment could induce eosinophilia and reduce
      Pneumocystis burden in CD4-depleted C57BL/6 and BALB/c mice, but not
      eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice. Taken together, these results
      demonstrate that an early role of CD4(+) T cells is to recruit eosinophils to the
      lung and that eosinophils are a novel candidate for future therapeutic
      development in the treatment of Pneumocystis pneumonia in the immunosuppressed
      population. 

PMID- 25994970
TI  - Temporal dynamics of musical emotions examined through intersubject synchrony of
      brain activity.
AB  - To study emotional reactions to music, it is important to consider the temporal
      dynamics of both affective responses and underlying brain activity. Here, we
      investigated emotions induced by music using functional magnetic resonance
      imaging (fMRI) with a data-driven approach based on intersubject correlations
      (ISC). This method allowed us to identify moments in the music that produced
      similar brain activity (i.e. synchrony) among listeners under relatively natural
      listening conditions. Continuous ratings of subjective pleasantness and arousal
      elicited by the music were also obtained for the music outside of the scanner.
      Our results reveal synchronous activations in left amygdala, left insula and
      right caudate nucleus that were associated with higher arousal, whereas positive
      valence ratings correlated with decreases in amygdala and caudate activity.
      Additional analyses showed that synchronous amygdala responses were driven by
      energy-related features in the music such as root mean square and dissonance,
      while synchrony in insula was additionally sensitive to acoustic event density.
      Intersubject synchrony also occurred in the left nucleus accumbens, a region
      critically implicated in reward processing. Our study demonstrates the
      feasibility and usefulness of an approach based on ISC to explore the temporal
      dynamics of music perception and emotion in naturalistic conditions. 

PMID- 25994971
TI  - Sex differences in intrinsic brain functional connectivity underlying human
      shyness.
AB  - Shyness is a fundamental trait associated with social-emotional maladaptive
      behaviors, including many forms of psychopathology. Neuroimaging studies have
      demonstrated that hyper-responsivity to social and emotional stimuli occurs in
      the frontal cortex and limbic system in shy individuals, but the relationship
      between shyness and brain-wide functional connectivity remains incompletely
      understood. Using resting-state functional magnetic resonance imaging, we
      addressed this issue by exploring the relationship between regional functional
      connectivity strength (rFCS) and scores of shyness in a cohort of 61 healthy
      young adults and controlling for the effects of social and trait anxiety scores.
      We observed that the rFCS of the insula positively correlated with shyness scores
      regardless of sex. Furthermore, we found that there were significant sex-by
      shyness interactions in the dorsal anterior cingulate cortex and insula (two core
      nodes of the salience network) as well as the subgenual anterior cingulate
      cortex: the rFCS values of these regions positively correlated with shyness
      scores in females but negatively correlated in males. Taken together, we provide
      evidence for intrinsic functional connectivity differences in individuals with
      different degrees of shyness and that these differences are sex-dependent. These
      findings might have important implications on the understanding of biological
      mechanisms underlying emotional and cognitive processing associated with shyness.

PMID- 25994973
TI  - Barriers to work-life balance for hospital nurses.
AB  - Nurses are loyal to their patients and coworkers. They often put the needs of
      others before their own and sometimes even before the needs of their families.
      This concern for others can cause conflicts that manifest as stress. Of the more
      than 2 million nurses in the United States, more than 62% work in hospitals.
      Hospitals are known to be both rewarding and stressful places to work. Like most
      workers, nurses face the challenge of balancing demands and achievements of work
      with those in their private lives. Hospital leaders can facilitate improved work
      life balance (WLB) for hospital nurses by using tools already in place. Equally
      important, nurses can use their knowledge and resources to nurse the nurse
      within, which can greatly improve their experience of WLB, independent of the
      demands of their work environment. 

PMID- 25994972
TI  - In vitro and in vivo antioxidant, cytotoxic, and anti-chronic inflammatory
      arthritic effect of selenium nanoparticles.
AB  - The toxicity of selenium (Se) as an antioxidant supplement in the treatment of
      arthritis is debatable. In this study, Dextrin stabilized Se nanoparticles (SeNP)
      of size 64 nm +/- 0.158 were used to explore its effects as a potent antioxidant
      with reduced toxicity in both in vitro and in vivo. In vitro toxicity of SeNP was
      determined using cytotoxicity assay. In vitro interactions of SeNP with DNA and
      protein was established. Subacute toxicity of SeNP was studied. Wistar rats with
      complete freunds adjuvant induced arthritis were used. Various concentrations of
      SeNP per kg body weight were fed orally daily upto to 21 days. Arthritic profile
      based on paw swelling, histopathological changes in joints, blood indices, and
      antioxidant enzymes level in organs such as liver, kidney, and spleen were
      investigated. Dextrin-SeNP when interacted with NIH-3T3 cells showed 15%
      cytotoxicity at 100 ug/mL whereas, bulk Se showed 95% at the same concentration.
      SeNP at 250 ug/mL showed protective effect on DNA. Interaction of SeNP with BSA
      showed increase in quenching of BSA fluorescence. SeNP did not show any subacute
      toxicity at concentration as high as 5 mg/kg b.w. in Wistar rats. SeNP at a
      concentration of 250 ug/kg b.w. acted as potent anti-inflammatory agent and
      significantly reduced (p < 0.05) arthritis induced parameters. The enzymatic
      antioxidant levels in liver, kidney, and spleen were restored significantly (p <
      0.05) at 500 ug/kg b.w. while CRP was regained to normal at concentration of 100
      ug/kg b.w. concluding SeNP at 500 ug/kg b.w. can be a potential antiarthritic
      drug supplement. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 104B: 993-1003, 2016.

PMID- 25994974
TI  - Effectiveness of a neck stretching intervention on nurses' primary headaches.
AB  - This study examined the effects of a neck stretching exercise intervention on
      nurses' primary headaches. Using a pretest and posttest two-group design, a total
      of 60 female staff nurses employed by a medical center in Taiwan were selected by
      convenience sampling. Participants in the experimental group (N=30) practiced
      neck stretching exercises while experiencing headaches. The participants in the
      control group (N=30) managed their headaches as usual. A structured questionnaire
      was used to collect data on headache intensity at baseline, and at 30 minutes and
      1 hour after intervention. Decrease in headache intensity of the experimental
      group was significantly larger than that of the control group. Neck stretching
      exercises is an effective method for treating primary headaches.

PMID- 25994975
TI  - Supervisors' support for nurses' meal breaks and mental health.
AB  - Meal breaks promote occupational health and safety; however, less is known about
      supervisors' support for nurses' meal breaks. In this study, the researchers
      tested whether the frequency of meal breaks was positively related to
      supervisors' support of nurses' meal breaks, and whether more frequent meal
      breaks were associated with less psychological distress. This study is based on a
      cross-sectional survey of 1,595 hospital nurses working on 85 units supervised by
      nursing directors. Specific meal-break support was measured at the nursing
      director level; frequency of meal breaks and psychological distress were measured
      at the individual nurse level. Multilevel adjusted models showed a positive
      association between supervisors' support for meal breaks and the frequency of
      nurses' meal breaks (beta=.16, p<.001). Moreover, nurses who took meal breaks
      more frequently reported lower psychological distress (beta=-.09, p<.05). Meal
      breaks might be daily opportunities to promote mental health and fatigue recovery
      and provide downtime.

PMID- 25994976
TI  - Smoking among Spanish workers after smoking regulation.
AB  - The aim of this study was to determine the prevalence of smoking among Spanish
      workers after a new smoking regulation became law. The researchers conducted a
      retrospective study with a worker sample. Information was collected via health
      examinations of 185 adults with a mean age of 35.93+/-9.13 for men and 36.16+/
      9.52 for women who agreed to participate in the study in 2010, 2011, and 2012.
      The percentages of occasional smokers, light smokers, moderate smokers, and heavy
      smokers were compared by year for men and women. In 2010, 18% of women smokers
      were occasional, 45% light, 27% moderate, and 10% heavy smokers. Twenty-two
      percent of male smokers were occasional, 16% light, 28% moderate, and 34% heavy
      smokers. In 2011, 12% of ex-smokers were women and 14% were men. In 2012, 30% of
      ex-smokers were women and 22% were men. In conclusion, the percentage of ex
      smokers has increased in this sample after the anti-smoking law was enacted.

PMID- 25994977
TI  - Developing blended online and classroom strategies to deliver an occupational
      health nursing overview course in a multi-state region in the United States.
AB  - This article describes how hybrid online and classroom learning approaches were
      used to design and offer an occupational health nursing review course throughout
      a multi-state region of the northwest United States. In response to demand from
      practicing occupational health nurses for board certification preparation, a
      series of asynchronous and synchronous continuing education modules was created
      covering a range of occupational health nursing topics. This review course
      illustrates how innovative educational delivery models can serve the needs of
      occupational health nurses challenged by geographic and time constraints. 

PMID- 25994979
TI  - Five steps to increasing utilization of your Employee Assistance Program.
AB  - Despite increased stress and free services, the national average for EAP use
      within a company continues to be 3% to 4%. This article describes the steps one
      company has taken to achieve a 16% utilization rate for the last 3 years. 

PMID- 25994980
TI  - Freeze drying of L-arginine/sucrose-based protein formulations, part I: influence
      of formulation and arginine counter ion on the critical formulation temperature,
      product performance and protein stability.
AB  - The objective of this study was to investigate product performance of freeze
      dried l-arginine/sucrose-based formulations under variation of excipient weight
      ratios, l-arginine counter ions and formulation pH as a matrix to stabilize a
      therapeutic monoclonal antibody (MAb) during freeze drying and shelf life.
      Protein and placebo formulations were lyophilized at aggressive primary drying
      conditions and key attributes of the freeze dried solids were correlated to their
      thermal properties and critical formulation temperature. Stability (physical)
      during processing and long-term storage of the MAb in different formulations was
      assessed by SE-HPLC. Thermal properties of the mixtures were greatly affected by
      the type of l-arginine counter ion. High glass transition temperatures were
      achieved by adding multivalent acids, whereas the temperature values
      significantly decreased in the presence of chloride ions. All mixtures were
      stable during freeze drying, but storage stability varied for the different
      preparations and counter ions. For l-arginine-based formulations, the protein was
      most stable in the presence of chloride ion, showing no obvious correlation to
      estimated global mobility of the glass. Besides drying behavior and thermal
      properties of the freeze dried solids, the counter ion of l-arginine must be
      considered relevant for protein shelf life stability.

PMID- 25994982
TI  - Influence of maternal, infant, and collection characteristics on high-quality
      cord blood units in Guangzhou Cord Blood Bank.
AB  - BACKGROUND: The operation of cord blood banks (CBBs) requires immense labor,
      material, and financial resources. Thus, increasing the ratio of high-quality
      cord blood units (HQCBUs) in storage that are qualified for clinical use is
      critical for the efficient use of limited resources. Understanding the factors
      that contribute to HQCBUs, including maternal, fetal, and processing conditions,
      may improve the number of HQCBUs in storage. STUDY DESIGN AND METHODS: The
      maternal, fetal, and processing conditions of 4613 CBUs at the Guangzhou Cord
      Blood Bank were analyzed retrospectively to determine their effect on HQCBUs. All
      CBUs were obtained following strict standard operation procedures. RESULTS:
      Several factors may contribute to HQCBUs: fetal age older than 37 gestational
      weeks, female fetus, large cord blood (CB) volume (>80 mL), high birthweight
      (>3500 g), vaginal delivery, and a shorter amount of time between CB collection
      and processing (12 hr). We report for the first time that alpha-thalassemia
      carriers exhibit a postprocessing total nucleated cell count (p-TNCC) increase to
      at least 1.25 * 10(9) and an increase of the CD34+ cell count to at least 6.01 *
      10(6) . Meconium-stained amniotic fluid and mothers younger than 25 years of age
      exhibited increased p-TNCC to at least 1.25 * 10(9) , and colony-forming units
      increased to at least 23.24 * 10(5) . CONCLUSIONS: We identified several factors
      that affect HQCBUs. These results may be used as a reference for updating CB
      collection strategies, with priority given to collecting CBUs from female fetuses
      older than 37 gestational weeks, at high birthweight, and born by vaginal
      delivery from mothers younger than 25 years of age, especially newborns with one
      parent carrying the trait or with meconium-stained amniotic fluid. The collected
      CBUs should be sent to the laboratory as soon as possible for priority
      processing, which will help to increase the number and ratio of HQCBUs and the
      effective use of CBB resources.

PMID- 25994981
TI  - Generating Virtual Patients by Multivariate and Discrete Re-Sampling Techniques.
AB  - PURPOSE: Clinical Trial Simulations (CTS) are a valuable tool for decision-making
      during drug development. However, to obtain realistic simulation scenarios, the
      patients included in the CTS must be representative of the target population.
      This is particularly important when covariate effects exist that may affect the
      outcome of a trial. The objective of our investigation was to evaluate and
      compare CTS results using re-sampling from a population pool and multivariate
      distributions to simulate patient covariates. METHODS: COPD was selected as
      paradigm disease for the purposes of our analysis, FEV1 was used as response
      measure and the effects of a hypothetical intervention were evaluated in
      different populations in order to assess the predictive performance of the two
      methods. RESULTS: Our results show that the multivariate distribution method
      produces realistic covariate correlations, comparable to the real population.
      Moreover, it allows simulation of patient characteristics beyond the limits of
      inclusion and exclusion criteria in historical protocols. CONCLUSION: Both
      methods, discrete resampling and multivariate distribution generate realistic
      pools of virtual patients. However the use of a multivariate distribution enable
      more flexible simulation scenarios since it is not necessarily bound to the
      existing covariate combinations in the available clinical data sets.

PMID- 25994983
TI  - Acculturation and dietary patterns among residents of Surinamese origin in the
      Netherlands: the HELIUS dietary pattern study.
AB  - OBJECTIVE: Insight into the role of acculturation in dietary patterns is
      important to inform the development of nutrition programmes that target ethnic
      minority groups. Therefore, the present study aimed to investigate how the
      adherence to dietary patterns within an ethnic minority population in the
      Netherlands varies by acculturation level compared with the host population.
      DESIGN: Cross-sectional study using data of the HELIUS study. Dietary patterns
      were assessed with an ethnic-specific FFQ. Acculturation was operationalized
      using unidimensional proxies (residence duration, age at migration and generation
      status) as well as on the basis of the bidimensional perspective, defined by four
      distinct acculturation strategies: assimilation, integration, separation and
      marginalization. SETTING: Amsterdam, the Netherlands. SUBJECTS: Participants of
      Dutch (n 1370) and Surinamese (n 1727) origin. RESULTS: Three dietary patterns
      were identified: (i) 'noodle/rice dishes and white meat' (traditional Surinamese
      pattern); (ii) 'red meat, snacks and sweets'; and (iii) 'vegetables, fruit and
      nuts'. Surinamese-origin respondents adhered more to the traditional Surinamese
      pattern than the other dietary patterns. Neither the unidimensional proxies nor
      the bidimensional acculturation strategies demonstrated consistent associations
      with dietary patterns. CONCLUSIONS: The lack of consistent association between
      acculturation and dietary patterns in the present study indicates that dietary
      patterns are quite robust. Understanding the continued adherence to traditional
      dietary patterns when developing dietary interventions in ethnic minority groups
      is warranted.

PMID- 25994987
TI  - [Evaluation of antibiotic treatments for urinary tract infections in the elderly,
      especially regarding the effect on extended spectrum beta-lactamase producing
      (ESBL-) Escherichia coli: A comparison between meropenem and alternatives].
AB  - BACKGROUND: An increasing incidence of extended-spectrum beta-lactamase (ESBL-)
      producing Escherihia Coli poses a difficult problem for clinicians to establish
      an optimal strategy for the effective antibiotic treatment of urinary tract
      infections (UTI). METHODS: (1) Fosfomycin/minocycline (FOM/MINO) or
      rifampicin/sulfamethoxazole-trimethoprim (RFP/ST) combinations and (2)
      levofloxacin (LVFX) alone were used as an internal medication, and (3)
      cefoperazone/sulbactam (CPZ/SBT) and (4) meropenem (MEPM) were administered
      through intravenous injection. The selection of antibiotics was done empirically,
      according to the history and severity of illness and urinary findings, and the
      presence of comobidities. The efficacy of the treatment was determined by the
      absence of any pathogenic bacteria from a urinary culture after treatment.
      RESULTS: ESBL-producing and LVFX resistant non-ESBL producing E. coli were
      detected by an initial urinary culture in 33 and 10%, respectively, of the
      specimens before treatment. All the ESBL-producing E. Coli colonies were
      resistant against LVFX. The efficacy of the treatment was 9/11 (82%) in the
      FOM/MINO-RFP/ST group, 9/14 (64%) in the LVFX group, 9/16 (56%) in the CPZ/SBT
      group, and 19/27 (70%) in the MEPM group. In the FOM/MINO?RFP/ST group, ESBL
      producing E. Coli were detected in the urine before treatment in 5 out of 16
      patients and those E. coli disappeared after treatment in all 5 patients. In the
      LVFX group, the drug was changed to MEPM in 6 out of 15 patients soon after the
      presence of ESBL-producing/LVFX resistant E. Coli was identified by a urinary
      culture. In the CPZ/SBT group, ESBL-producing and/or LVFX-resistant E. coli
      disappeared in 4 out of 6 cases, while they were newly found in post-treatment
      urine cultures in 2 patients. In the MEPM group, 15 out of 28 patients initially
      had ESBL-producing/LVFX resistant E. Coli and those drug-resistant E. Coli
      disappeared from their urine after treatment in all patients. The drug
      susceptibility test of the urinary culture from all the patients with UTI showed
      CPZ/SBT-resistant colonies to be found in 19 out of 32 specimens, while AMPC/CVA
      resistant ones were found in 9 out of 32 of ESBL-producing E. Coli. CONCLUSIONS:
      Our present study demonstrates that FOM/MINO or ST combinations were effective in
      the treatment of ESBL-producing E. Coli in mild cases of UTI and MEPM in severe
      cases. When using beta-lactam/beta-lactamase inhibitor combinations, the effect
      should be ascertained by examining post-treatment urinary specimens, because of
      the presence of ESBL-producing E. Coli strains which are resistant to those
      antibiotics.

PMID- 25994984
TI  - Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens
      Implantation and Wavefront-guided Laser in Situ Keratomileusis.
AB  - This study aimed to investigate the effect of myopic defocus on visual acuity
      after phakic intraocular lens (IOL) implantation and wavefront-guided laser in
      situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes
      undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg
      LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic
      and non-cycloplegic correction. We also calculated the modulation transfer
      function by optical simulation and estimated visual acuity from Campbell &Green's
      retinal threshold curve. Visual acuity in the phakic IOL group was significantly
      better than that in the wfg-LASIK group at myopic defocus levels of 0, -1, and -2
      D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus
      of -3 D (p = 0.30). Similar results were also obtained in a cycloplegic
      condition. Decimal visual acuity values at a myopic defocus of 0, -1, -2, and -3
      D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the
      phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group,
      respectively. From clinical and optical viewpoints, phakic IOL implantation was
      superior to wfg-LASIK in terms of the postoperative visual performance, even in
      the presence of low to moderate myopic regression.

PMID- 25994988
TI  - [Effects of Square-Stepping Exercise inducing activation of the brain's cognitive
      function in community-dwelling older Japanese females--Focus on the baseline
      cognitive function level and age].
AB  - AIM: The purpose of this study was to investigate whether the degree of
      improvement in cognitive function achieved with an exercise intervention in
      community-dwelling older Japanese women is affected by the participant's baseline
      cognitive function and age. METHODS: Eighty-eight women (mean age: 70.5+/-4.2
      years) participated in a prevention program for long-term care. They completed
      the Square-Stepping Exercise (SSE) program once a week, 120 minutes/session, for
      11 weeks. We assessed participants' cognitive function using 5 cognitive tests (5
      Cog) before and after the intervention. We defined cognitive function as the 5
      Cog total score and defined the change in cognitive function as the 5-cog post
      score minus the pre-score. We divided participants into four groups based on age
      (<=69 years or >=70 years) and baseline cognitive function level (above vs. below
      the median cognitive function level). We conducted two-way analysis of variance.
      RESULTS: All 4 groups improved significantly in cognitive function after the
      intervention. There were no baseline cognitive function level*age interactions
      and no significant main effects of age, although significant main effects of
      baseline cognitive function level (P=0.004, eta(2)=0.09) were observed.
      CONCLUSION: Square-Stepping Exercise is an effective exercise for improving
      cognitive function. These results suggest that older adults with cognitive
      decline are more likely to improve their cognitive function with exercise than if
      they start the intervention with high cognitive function. Furthermore, during an
      exercise intervention, baseline cognitive function level may have more of an
      effect than a participant's age on the degree of cognitive improvement.

PMID- 25994989
TI  - [Routes of nutrition and types of diet among dependent community-dwelling older
      care recipients and the relevance to mortality and hospitalization].
AB  - AIM: To clarify the routes of nutrition and types of diet and their relevance to
      the risk of mortality and hospitalization among community-dwelling dependent
      elderly provided various home care services under the long-term care insurance
      program. METHODS: The present study consisted of the collection of baseline data
      of participants in the Nagoya Longitudinal Study of the Frail Elderly (NLS-FE)
      and data regarding mortality and hospitalization during a three-year follow-up
      period. The study population consisted of 1,872 subjects, and the baseline data
      included demographic characteristics, basic activities of daily living (ADLs),
      comorbidities, nutritional routes and types of diet, which were evaluated by
      trained visiting nurses. RESULTS: Among the participants, 1,786 were on oral
      nutrition (solid regular-texture diet: 1,487 (79.5%); modified-texture diet
      (minced/pureed texture): 299 (16.0%), 82 (4.4%) were on enteral nutrition and
      four (0.2%) were on parenteral nutrition. During the three-year follow-up period,
      453 participants died and 798 participants experienced admission to the hospital
      (pneumonia-related death and hospitalization: n=103 and 155, respectively). Cox
      regression models revealed that a modified-texture diet and tube feeding are
      associated with all-cause mortality and hospitalization. In particular, feeding
      tube use showed a high risk of pneumonia-related mortality and hospitalization,
      even after adjusting for potential confounders, including comorbidities and the
      ADL status.

PMID- 25994990
TI  - [A Case of an Elderly Diabetic Patient Developing Wernicke Encephalopathy without
      Alcohol Abuse or an Unbalanced Diet].
AB  - A 70-year-old man with a 28-year history of type 2 diabetes mellitus was admitted
      due to persistent vomiting and neurological abnormalities in Nov 2012. He had
      developed gait disturbance and diplopia for six months during antiplatelet
      therapy, which was initiated following the diagnosis of a cerebellar infarction
      in June 2012. He had nystagmus, truncal ataxia and an ocular motility disorder,
      and the MRI study showed increased FLAIR and DWI signals in the peri-third
      ventricle and periaqueductal region, in addition to the cerebellar vermis.
      Wernicke encephalopathy was suspected according to his symptoms, and thiamine
      administration dramatically improved his condition. He did not have a history of
      alcohol abuse or poor eating habits; however, various coexisting factors,
      including diabetes mellitus, pyloric stenosis and the use of antiulcer drugs and
      insulin, were considered to be responsible for Wernicke encephalopathy. This case
      demonstrates the importance of distinguishing Wernicke encephalopathy from
      cerebrovascular disease in elderly patients. 

PMID- 25994994
TI  - Dose tailoring of dabigatran etexilate: obvious or excessive?
AB  - INTRODUCTION: Dabigatran etexilate is used for preventing blood clots and tends
      to replace older anticoagulants in many of their indications. However, the 'one
      dose fits all' policy is subject to criticism. Recent findings assert the anxiety
      of the scientific community concerning the pharmacokinetic properties of
      dabigatran etexilate, that is, an important interindividual variability including
      an important genetic variant with a significant dependence of the renal function
      as route of elimination. AREAS COVERED: This meta-opinion provides an overview of
      the current knowledge and evidence on the dose tailoring of dabigatran etexilate.
      It also discusses the remaining challenges to benefit from this perspective
      strategy to enhance the benefit-risk balance of dabigatran etexilate. Data were
      searched in the published literature and on regulatory agencies' websites.
      Additionally, unpublished data were searched and discussed. EXPERT OPINION:
      Causality between dabigatran exposure and bleeding risk is now established and
      recommendations on how to best estimate the drug exposure are published.
      Additionally, simulating studies revealed that a dose adaptation based on
      dabigatran plasma concentration estimations could improve the benefit-risk
      profile of the drug. This accumulating evidence suggests that some patients under
      dabigatran etexilate may benefit from a tailoring of the dose beyond the ones
      already proposed by the manufacturer.

PMID- 25994995
TI  - Serum uric acid may not be involved in the development of preeclampsia.
AB  - Higher serum levels of uric acid are associated with preeclampsia and may signal
      an early change in preeclampsia. However there is less evidence suggesting there
      is a meaningful association between uric acid and the development of
      preeclampsia. A total of 877 women with preeclampsia at presentation and 580
      normotensive pregnancies were retrospectively recruited from January 2009 to May
      2014. In addition, 5556 pregnant women were also prospectively recruited from
      September 2012 to December 2013. Retrospective serum levels of uric acid were
      obtained from women with preeclampsia at the time of presentation (n=877), and
      serum levels of uric acid in the first, second and third trimester were
      prospectively collected in women who later developed preeclampsia (n=78), as well
      as those who did not (n=5478). The serum levels of uric acid were significantly
      increased in women with preeclampsia at presentation from retrospective samples
      and this increase correlated with the time of onset and the severity of
      preeclampsia. However, in prospective samples, serum levels of uric acid were not
      increased in the first and second trimesters in women who later developed
      preeclampsia compared with those who did not. The serum level of uric acid in the
      first and second trimesters in women who developed preeclampsia was not
      different. Our results demonstrate that the serum levels of uric acid were only
      increased after the presentation of clinical symptoms of preeclampsia. Therefore,
      it is likely that uric acid is not involved in the development of preeclampsia
      and cannot be an early prediction biomarker of this disease. 

PMID- 25994996
TI  - The clinical significance and costs of herbs and food supplements used by
      complementary and alternative medicine for the treatment of cardiovascular
      diseases and hypertension.
AB  - Complementary and alternative medicine (CAM) is widely used by people in the
      United States and other countries for the treatment of health conditions that
      include hypertension (HTN), cardiovascular disease (CVD), heart failure,
      hyperlipidemia and other condtions. The visits to CAM practitioners result in
      significant out-of-pocket expenses, as CAM is not covered by health insurance in
      the majority of cases. The reasons for this are that the products used are not
      closely regulated by governmental regulatory agencies and lack scientific
      evidence about their effectiveness and safety. The people regard these products
      as being 'natural' and, consequently, safe. However, there is evidence that these
      products can be contaminated and adulterated with other substances and could
      cause harm to the persons who take them. The responsibility falls on the health
      professionals, who should become familiar with the various CAM products, inquire
      their patients whether they taking any of these products and advise them
      accordingly. This review is based on a recent statement issued by the American
      Medical for the use of CAM for the treatment of HTN. For its preparation, a
      Medline search of the English language literature was performed between 2010 and
      2014 restricted in the use of CAM for CVD and HTN, and from the 88 abstracts
      reviewed, 23 pertinent papers were selected. These papers together with
      collateral literature will be discussed in this review regarding CAM and CAM
      products on their effectiveness and safety for the treatment of CVD and HTN. 

PMID- 25994998
TI  - Toxicity in relation to mode of action for the nematode Caenorhabditis elegans:
      Acute-to-chronic ratios and quantitative structure-activity relationships.
AB  - Acute-to-chronic ratios (ACRs) and quantitative structure-activity relationships
      (QSARs) are of particular interest in chemical risk assessment. Previous studies
      focusing on the relationship between the size or variation of ACRs to substance
      classes and QSAR models were often based on data for standard test organisms,
      such as daphnids and fish. In the present study, acute and chronic toxicity tests
      were performed with the nematode Caenorhabditis elegans for a total of 11
      chemicals covering 3 substance classes (nonpolar narcotics: 1-propanol, ethanol,
      methanol, 2-butoxyethanol; metals: copper, cadmium, zinc; and carbamates:
      methomyl, oxamyl, aldicarb, dioxacarb). The ACRs were variable, especially for
      the carbamates and metals, although there was a trend toward small and less
      variable ACRs for nonpolar narcotic substances. The octanol-water partition
      coefficient was a good predictor for explaining acute and chronic toxicity of
      nonpolar narcotic substances to C. elegans, but not for carbamates. Metal
      toxicity could be related to the covalent index chim2r. Overall, the results
      support earlier results from ACR and QSAR studies with standard freshwater test
      animals. As such C. elegans as a representative of small soil/sediment
      invertebrates would probably be protected by risk assessment strategies already
      in use. To increase the predictive power of ACRs and QSARs, further research
      should be expanded to other species and compounds and should also consider the
      target sites and toxicokinetics of chemicals.

PMID- 25994997
TI  - Relationship between serum levels of endogenous secretory RAGE and blood pressure
      in male nondiabetic patients with obstructive sleep apnea.
AB  - The interaction of advanced glycation end products (AGE) and their specific cell
      surface receptor (RAGE) has an important role in the pathogenesis of
      cardiovascular disease and diabetic complications. Two isoforms of C-truncated
      RAGE, soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE), may prevent
      activation of RAGE signaling by acting as decoys. This study investigated whether
      serum esRAGE and sRAGE levels are associated with blood pressure in nondiabetic
      patients with obstructive sleep apnea (OSA). Male nondiabetic patients (n=139)
      with OSA were enrolled. Serum esRAGE and sRAGE levels were examined using enzyme
      linked immunosorbent assay. Three consecutive seated systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) measurements were obtained at 5-min
      intervals in the morning. In univariate analysis, there was a significant
      correlation between serum esRAGE and SBP or DBP, but not between serum sRAGE and
      SBP or DBP. Multiple regression analysis showed that SBP was independently
      associated with waist circumference, HbA1c, minimum SaO2 and serum esRAGE, and
      that DBP was independently associated with low-density lipoprotein cholesterol,
      apnea-hypopnea index, serum AGE and body mass index, but not with serum esRAGE.
      These results indicated that serum esRAGE levels were inversely associated with
      blood pressure, especially SBP, in male nondiabetic patients with OSA. esRAGE may
      have a protective role against hypertension in patients with OSA, and it may be a
      novel biomarker for OSA patients at high risk of developing cardiovascular
      diseases. 

PMID- 25994999
TI  - Simultaneous quantification of phencynonate and its active metabolite N-demethyl
      phencynonate in human plasma using liquid chromatography and isotope-dilution
      mass spectrometry.
AB  - A sensitive and selective liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was developed to simultaneously quantify phencynonate (PCN) and its
      major metabolite N-demethyl phencynonate (DM-PCN) in human plasma. Following one
      step liquid-liquid extraction, the analytes were separated on a reversed-phase
      C18 column. Methanol and 0.02% formic acid in 10 mM ammonium acetate (62:38, v/v)
      was used as isocratic mobile phase at a flow-rate of 0.3 mL/min. An API 5000
      tandem mass spectrometer equipped with a Turbo IonSpray ionization source was
      used as the detector and was operated in the positive ion mode. Multiple reaction
      monitoring using the transition of m/z 358.4 -> m/z 156.2, m/z 344.4 -> m/z
      142.2, and m/z 361.3 -> m/z 159.2 was performed to quantify PCN, DM-PCN, and the
      internal standard (D3 -PCN), respectively. This approach showed a lower limit of
      quantification of 10 pg/mL and 25 pg/mL for PCN and DM-PCN in plasma,
      respectively. This sensitivity was at least 50-fold superior to previously
      reported ones and thus enabled the approach well applicable to low-dose
      pharmacokinetic studies. The intra- and inter-day precisions were less than 14.2
      % at each QC level for both PCN and DM-PCN. The inter-day relative errors ranged
      from -1.9% to -4.9% for PCN, and from 0.6% to 6.4% for DM-PCN. As a proof of
      principle, the validated method was successfully applied to simultaneous
      quantification of circulating PCN and DM-PCN in healthy subjects after a single
      oral administration of 2 mg phencynonate hydrochloride pellet.

PMID- 25995000
TI  - [The effect of different working postures while felling a tree with a chain-saw
      on trunk muscles' activity].
AB  - PURPOSE: Many forestry workers who use chain-saws suffer from low back pain.
      Previous studies have reported that low back pain is related to the working
      postures while felling a tree with a using chain-saws. However, no previous study
      has investigated trunk muscle activities during work. The purpose of this study
      was to clarify the relationship between working postures while holding a chain
      saw, and trunk muscles activities as measured by surface electromyography (EMG).
      METHOD: Subjects were 10 males who were not forestry workers. Four task postures
      while holding a chain-saw were tested: standing, 30(o) trunk flexion, 90(o) trunk
      flexion and half-kneeling. EMG recordings were obtained bilaterally of the lumbar
      paraspinal (LP) muscles and rectus abdominis (RA) muscles. Raw EMG data were
      processed by integrating the EMG and normalizing them to %MVC. The paired t-test
      was used to detect statistical differences in the activities between the right
      and left LP muscles and RA muscles. One-factor repeated measures ANOVA was used
      to compare the bilateral LP and RA muscle activities among the 4 different
      postures. The significance level was set to less than 5%. RESULTS: In the half
      kneeling posture, the right LP muscle activity was 14.7% higher than the left LP
      muscle activity (p<0.05); however, there were no significant differences in
      muscle activities among the other postures. The right LP muscle activity of 30(o)
      trunk flexion posture was 25.6% higher than that of the standing posture, and
      14.2% higher than that of half-kneeling posture (p<0.05). The bilateral LP muscle
      activities of the 90(o) trunk flexion posture were the highest of the 4 postures,
      16.7% higher than the half-kneeling posture (p<0.05) right LP muscle activity.
      There was a tendency of increase in the left LP muscle activity when trunk
      flexion angle increased, but no significant differences among the 4 postures were
      found. The bilateral RA muscle activities were low and did not significantly
      differ among the 4 postures. CONCLUSIONS: This study showed that when the trunk
      is flexed, the LP muscle activities change asymmetrically, with the right LP
      muscle activity increasing significantly compared to the standing posture and the
      half-kneeing posture, but there was no significant difference in the left LP
      muscle activity. These results suggest that working postures that involve trunk
      flexion while felling a tree with a holding chain-saw may lead to increased
      loading of the LP muscles.

PMID- 25995002
TI  - Erratum to: Sexual Mixing in Shanghai: Are Heterosexual Contact Patterns
      Compatible With an HIV/AIDS Epidemic?

PMID- 25995001
TI  - Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4
      monoclonal antibody, mogamulizumab.
AB  - A 57-year-old male with acute-type adult T cell leukemia-lymphoma (ATL) developed
      persistent watery, non-bloody diarrhea at a volume of 2-3 L/day following the
      administration of the anti-CC chemokine receptor 4 (CCR4) monoclonal antibody,
      mogamulizumab. An extensive examination revealed the absence of any pathogenic
      bacteria or parasites in his stool. Biopsied specimens from the colonic mucosa
      contained many small nests of apoptotic bodies in the colonic glands, which
      mimicked acute-colonic graft-versus-host disease. Activation of the auto-reactive
      immune system due to the depletion of regulatory T-cells by mogamulizumab was
      suspected as causative. Special attention should be paid to the risk of unique
      immune-related adverse events induced by mogamulizumab.

PMID- 25995003
TI  - Perovskites.

PMID- 25995004
TI  - Where does it FIT? The roles of fecal testing and colonoscopy in colorectal
      cancer screening.

PMID- 25995006
TI  - Apterous A modulates wing size, bristle formation and patterning in Nilaparvata
      lugens.
AB  - Apterous A (apA), a member of the LIM-homeobox gene family, plays a critical role
      in the development of wing. The achaete-scute Complex (AS-C) encodes basic helix
      loop-helix (bHLH) transcription factors and functions in bristle development. In
      the present study, we cloned apA (NlapA) and an achaete-scute homologue (NlASH)
      from N. lugens. Levels of NlapA and NlASH were higher in nymphs than adults, with
      particularly high expression in the thorax of nymphs. NlapA expressed more highly
      in nymphs of the macropterous strain (MS) than those of the brachypterous strain
      (BS) at 2(nd) and 4(th) instar. Knockdown of NlapA and NlASH in vivo generated
      similar phenotypic defects in the wing (loss-of-bristles, twisted or erect wing).
      Silencing of NlapA in nymphs of MS led to decreased wing size in adults.
      Moreover, depletion of NlapA suppressed expression of NlDl, Nlsal, Nlser, Nlvg
      and Nlwg, both in MS and BS, but induced differential responses of Nlubx and
      Nlnotch expression between MS and BS. Notably, expression of NlASH was regulated
      by NlapA. These results collectively indicate that NlapA is an upstream modulator
      of wing size, bristle formation and patterning. Further studies on DNA-protein
      and protein-protein interactions are required to elucidate NlapA-mediated
      regulation of wing development. 

PMID- 25995007
TI  - Dispelling dogma and misconceptions regarding the most pharmacologically
      targetable source of reactive species in inflammatory disease, xanthine
      oxidoreductase.
AB  - Xanthine oxidoreductase (XOR), the molybdoflavin enzyme responsible for the
      terminal steps of purine degradation in humans, is also recognized as a
      significant source of reactive species contributory to inflammatory disease. In
      animal models and clinical studies, inhibition of XOR has resulted in diminution
      of symptoms and enhancement of function in a number of pathologies including
      heart failure, diabetes, sickle cell anemia, hypertension and ischemia
      reperfusion injury. For decades, XOR involvement in pathologic processes has been
      established by salutary outcomes attained from treatment with the XOR inhibitor
      allopurinol. This has served to frame a working dogma that elevation of XOR
      specific activity is associated with enhanced rates of reactive species
      generation that mediate negative outcomes. While adherence to this narrowly
      focused practice of designating elevated XOR activity to be "bad" has produced
      some benefit, it has also led to significant underdevelopment of the processes
      mediating XOR regulation, identification of alternative reactants and products as
      well as micro-environmental factors that alter enzymatic activity. This is
      exemplified by recent reports: (1) identifying XOR as a nitrite reductase and
      thus a source of beneficial nitric oxide ((*)NO) under in vivo conditions similar
      to those where XOR inhibition has been assumed an optimal treatment choice, (2)
      describing XOR-derived uric acid (UA) as a critical pro-inflammatory mediator in
      vascular and metabolic disease and (3) ascribing an antioxidant/protective role
      for XOR-derived UA. When taken together, these proposed and countervailing
      functions of XOR affirm the need for a more comprehensive evaluation of product
      formation as well as the factors that govern product identity. As such, this
      review will critically evaluate XOR-catalyzed oxidant, (*)NO and UA formation as
      well as identify factors that mediate their production, inhibition and the
      resultant impact on inflammatory disease. 

PMID- 25995008
TI  - The impact of p53 on DNA damage and metabolic activation of the environmental
      carcinogen benzo[a]pyrene: effects in Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice.
AB  - The tumour suppressor p53 is one of the most important cancer genes. Previous
      findings have shown that p53 expression can influence DNA adduct formation of the
      environmental carcinogen benzo[a]pyrene (BaP) in human cells, indicating a role
      for p53 in the cytochrome P450 (CYP) 1A1-mediated biotransformation of BaP in
      vitro. We investigated the potential role of p53 in xenobiotic metabolism in vivo
      by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with BaP. BaP-DNA adduct
      levels, as measured by (32)P-postlabelling analysis, were significantly higher in
      liver and kidney of Trp53(-/-) mice than of Trp53(+/+) mice. Complementarily,
      significantly higher amounts of BaP metabolites were also formed ex vivo in
      hepatic microsomes from BaP-pretreated Trp53(-/-) mice. Bypass of the need for
      metabolic activation by treating mice with BaP-7,8-dihydrodiol-9,10-epoxide
      resulted in similar adduct levels in liver and kidney in all mouse lines,
      confirming that the influence of p53 is on the biotransformation of the parent
      compound. Higher BaP-DNA adduct levels in the livers of Trp53(-/-) mice
      correlated with higher CYP1A protein levels and increased CYP1A enzyme activity
      in these animals. Our study demonstrates a role for p53 in the metabolism of BaP
      in vivo, confirming previous in vitro results on a novel role for p53 in CYP1A1
      mediated BaP metabolism. However, our results also suggest that the mechanisms
      involved in the altered expression and activity of the CYP1A1 enzyme by p53 in
      vitro and in vivo are different. 

PMID- 25995009
TI  - Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood
      pressure, adiposity, cholesterol metabolism and social interaction in mouse
      offspring.
AB  - Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated
      with carcinogenicity, fetotoxicity, psychological disorders and metabolic
      diseases, but the detrimental effects and mechanisms are not fully understood. We
      investigated the effect of exposing mouse mothers to DEHP, and the underlying
      mechanism, on blood pressure, obesity and cholesterol metabolism as well as
      psychological and learning behaviors in offspring. Tail-cuff plethysmography was
      used for blood pressure measurement; Western blot used was for phosphorylation
      and expression of protein; hematoxylin and eosin staining, Nissl staining and
      Golgi staining were used for histological examination. The serum levels of
      cholesterol, triglycerides and glucose were measured by blood biochemical
      analysis. Hepatic cholesterol and triglyceride levels were assessed by
      colorimetric assay kits. Offspring behaviors were evaluated by open-field
      activity, elevated plus maze, social preference test and Morris water maze.
      Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric
      oxide synthase and upregulated angiotensin type 1 receptor in offspring, which
      led to increased blood pressure. It led to obesity in offspring by increasing the
      size of adipocytes in white adipose tissue and number of adipocytes in brown
      adipose tissue. It increased the serum level of cholesterol in offspring by
      decreasing the hepatic capacity for cholesterol clearance. The impaired social
      interaction ability induced by maternal DEHP exposure might be due to abnormal
      neuronal development. Collectively, our findings provide new evidence that
      maternal exposure to DEHP has a lasting effect on the physiological functions of
      the vascular system, adipose tissue and nerve system in offspring. 

PMID- 25995010
TI  - To be credible, success in "reducing the use of animals in scientific research"
      must involve the use of fewer animals.

PMID- 25995011
TI  - Comparative costs of the Mouse Inoculation Test (MIT) and Virus Isolation in Cell
      Culture (VICC) for use in rabies diagnosis in Brazil.
AB  - The decision to use laboratory animals rather than in vitro methods is frequently
      based on the financial costs involved, so the objective of our study was to
      compare the costs of performing the Mouse Inoculation Test (MIT) and Virus
      Isolation in Cell Culture (VICC) for use in rabies diagnosis in Brazil. Based on
      observations of laboratory routines at the Pasteur Institute, Sao Paulo, we
      listed the fixed cost (FC) and variable cost (VC) items necessary to perform both
      tests. Considering that 200 MITs are equivalent to 350 VICC assays, in terms of
      facilities and staff-hours needed per month, we calculated, for both tests, the
      average total cost per sample, the costs of the implementation of the laboratory
      structure, and the costs of routine use. With regard to absolute values, the
      total cost was mainly influenced by FC items, as they represented 60% of the cost
      for the MIT and 86% of the cost for VICC. A sample analysed by the MIT costs
      around 205% more than one analysed by using VICC. The MIT costs 74% and 406% more
      than VICC, when implementation costs and routine use per month, respectively, are
      taken into account. Our results can assist in the resolution of costing disputes
      that could hinder the replacement of animals for rabies diagnosis in Brazil. The
      method demonstrated here might also be useful for cost comparisons in other
      situations where animal use still continues when validated alternatives exist. 

PMID- 25995012
TI  - Optimisation of the bovine whole in vitro embryo system as a sentinel for
      toxicity screening: a cadmium challenge.
AB  - Developmental toxicity testing could greatly benefit from the availability of an
      in vitro alternative model based on the use of animal embryos that have better
      human-like physiology than the currently-used alternative models. These current
      models are insufficient, as extrapolation of the results can be challenging.
      Therefore, an in vitro bovine embryo culture system was used to expose individual
      morulae to test substances, and to study developmental characteristics up to the
      blastocyst stage. Cadmium was chosen as the reference toxicant to investigate the
      sensitivity of the bovine morulae to various concentrations and exposure times.
      Oocytes from slaughterhouse-obtained bovine ovaries, were maturated, fertilised
      and cultured up until the morula stage. Morulae were exposed to different cadmium
      concentrations for 18 or 70 hours, and developmental competence, embryo quality
      and the expression of cadmium exposure-related genes were evaluated. Cadmium
      exposure hampered embryonic developmental competence and quality. Compared with
      the 18-hour exposure, the 70-hour exposure induced a 20-fold higher toxic
      response with regard to developmental competence and a more 'cadmium-typical'
      transcript expression. The bovine morula might be a promising tool for toxicity
      testing as, following exposure, the embryos reacted in a sensitive and 'cadmium
      typical' manner to our reference toxicant. 

PMID- 25995013
TI  - The EpiOcular Eye Irritation Test (EIT) for hazard identification and labelling
      of eye irritating chemicals: protocol optimisation for solid materials and the
      results after extended shipment.
AB  - The 7th Amendment to the EU Cosmetics Directive and the EU REACH Regulation have
      reinforced the need for in vitro ocular test methods. Validated in vitro ocular
      toxicity tests that can predict the human response to chemicals, cosmetics and
      other consumer products are required for the safety assessment of materials that
      intentionally, or inadvertently, come into contact with the eye. The EpiOcular
      Eye Irritation Test (EIT), which uses the normal human cell-based EpiOcularTM
      tissue model, was developed to address this need. The EpiOcular-EIT is able to
      discriminate, with high sensitivity and accuracy, between ocular
      irritant/corrosive materials and those that require no labelling. Although the
      original EpiOcular-EIT protocol was successfully pre-validated in an
      international, multicentre study sponsored by COLIPA (the predecessor to
      Cosmetics Europe), data from two larger studies (the EURL ECVAM-COLIPA validation
      study and an independent in-house validation at BASF SE) resulted in a
      sensitivity for the protocol for solids that was below the acceptance criteria
      set by the Validation Management Group (VMG) for eye irritation, and indicated
      the need for improvement of the assay's sensitivity for solids. By increasing the
      exposure time for solid materials from 90 minutes to 6 hours, the optimised
      EpiOcular-EIT protocol achieved 100% sensitivity, 68.4% specificity and 84.6%
      accuracy, thereby meeting all the acceptance criteria set by the VMG. In
      addition, to satisfy the needs of Japan and the Pacific region, the EpiOcular-EIT
      method was evaluated for its performance after extended shipment and storage of
      the tissues (4-5 days), and it was confirmed that the assay performs with similar
      levels of sensitivity, specificity and reproducibility in these circumstances. 

PMID- 25995014
TI  - How long must they suffer? success and failure of our efforts to end the animal
      tragedy in laboratories.
AB  - Scientific findings have revealed how much we have dramatically underestimated
      the intellectual, social and emotional capabilities of non-human animals,
      including their levels of self-consciousness and ability to suffer from
      psychological stress. In the 21st century, the field of animal ethics has evolved
      as a serious scientific discipline, and nowadays largely advocates that the way
      we treat animals, both legally and in practice, is morally wrong. Politics and
      legislation have reacted to these facts, to some extent, but neither current
      legislation nor current practice reflect the scientific and moral state-of-the
      art. Too often, the will to change things is watered down in the decision-making
      process, e.g. in the drafting of legislation. In the field of animal
      experimentation there have been many genuine efforts by various players, to
      advance and apply the principles behind the Three Rs. However, the fundamental
      problem, i.e. the overall number of animals sacrificed for scientific purposes,
      has increased. Clearly, if we are serious about our will to regard animal
      experimentation as an ethical and societal problem, we have to put much more
      emphasis on addressing the question of how to avoid the use of animals in
      science. To achieve this goal, certain issues need to be considered: a) the
      present system of ethical evaluation of animal experiments, including testing for
      regulatory purposes, needs to be reformed and applied effectively to meet the
      legal and moral requirements; b) animal testing must be avoided in future
      legislation, and existing legislation has to be revised in that regard; c)
      resources from animal-based research have to re-allocated toward alternatives;
      and d) the academic curricula must be reformed to foster and integrate ethical
      and animal welfare issues. 

PMID- 25995015
TI  - In vitro methodologies in ecotoxicological hazard assessment: the case of
      bioaccumulation testing for fish.

PMID- 25995016
TI  - Coffee in class: an alternative to animal experiments in pharmacology?

PMID- 25995017
TI  - Turning apples into oranges? The harm-benefit analysis and how to take ethical
      considerations into account.

PMID- 25995018
TI  - 16. The Three Rs: the way forward.

PMID- 25995019
TI  - Multi-institutional validation of a novel textural analysis tool for preoperative
      stratification of suspected thyroid tumors on diffusion-weighted MRI.
AB  - PURPOSE: Ultrasound-guided fine needle aspirate cytology fails to diagnose many
      malignant thyroid nodules; consequently, patients may undergo diagnostic
      lobectomy. This study assessed whether textural analysis (TA) could noninvasively
      stratify thyroid nodules accurately using diffusion-weighted MRI (DW-MRI).
      METHODS: This multi-institutional study examined 3T DW-MRI images obtained with
      spin echo echo planar imaging sequences. The training data set included 26
      patients from Cambridge, United Kingdom, and the test data set included 18
      thyroid cancer patients from Memorial Sloan Kettering Cancer Center (New York,
      New York, USA). Apparent diffusion coefficients (ADCs) were compared over regions
      of interest (ROIs) defined on thyroid nodules. TA, linear discriminant analysis
      (LDA), and feature reduction were performed using the 21 MaZda-generated texture
      parameters that best distinguished benign and malignant ROIs. RESULTS: Training
      data set mean ADC values were significantly different for benign and malignant
      nodules (P = 0.02) with a sensitivity and specificity of 70% and 63%,
      respectively, and a receiver operator characteristic (ROC) area under the curve
      (AUC) of 0.73. The LDA model of the top 21 textural features correctly classified
      89/94 DW-MRI ROIs with 92% sensitivity, 96% specificity, and an AUC of 0.97. This
      algorithm correctly classified 16/18 (89%) patients in the independently obtained
      test set of thyroid DW-MRI scans. CONCLUSION: TA classifies thyroid nodules with
      high sensitivity and specificity on multi-institutional DW-MRI data sets. This
      method requires further validation in a larger prospective study. Magnetic
      Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance.

PMID- 25995021
TI  - A Content Validity Study of AIMIT (Assessing Interpersonal Motivation in
      Transcripts).
AB  - Multi-motivational theories of human relatedness state that different
      motivational systems with an evolutionary basis modulate interpersonal
      relationships. The reliable assessment of their dynamics may usefully inform the
      understanding of the therapeutic relationship. The coding system of the Assessing
      Interpersonal Motivation in Transcripts (AIMIT) allows to identify in the
      clinical the activity of five main interpersonal motivational systems (IMSs):
      attachment (care-seeking), caregiving, ranking, sexuality and peer cooperation.
      To assess whether the criteria currently used to score the AIMIT are consistently
      correlated with the conceptual formulation of the interpersonal multi
      motivational theory, two different studies were designed. Study 1: Content
      validity as assessed by highly qualified independent raters. Study 2: Content
      validity as assessed by unqualified raters. Results of study 1 show that out of
      the total 60 AIMIT verbal criteria, 52 (86.7%) met the required minimum degree of
      correspondence. The average semantic correspondence scores between these items
      and the related IMSs were quite good (overall mean: 3.74, standard deviation:
      0.61). In study 2, a group of 20 naive raters had to identify each prevalent
      motivation (IMS) in a random sequence of 1000 utterances drawn from therapy
      sessions. Cohen's Kappa coefficient was calculated for each rater with reference
      to each IMS and then calculated the average Kappa for all raters for each IMS.
      All average Kappa values were satisfactory (>0.60) and ranged between 0.63
      (ranking system) and 0.83 (sexuality system). Data confirmed the overall
      soundness of AIMIT's theoretical-applicative approach. Results are discussed,
      corroborating the hypothesis that the AIMIT possesses the required criteria for
      content validity. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER
      MESSAGE: Assessing Interpersonal Motivations in psychotherapy transcripts as a
      useful tool to better understand links between motivational systems and
      intersubjectivity. A step forward in the knowledge of evolutionary cognitivism
      and a contribution to the bio-psycho-social model of human relatedness and
      interpersonal neurobiology.

PMID- 25995020
TI  - Autism Spectrum Disorder Symptoms and Comorbidity in Emerging Adults.
AB  - Autism spectrum disorder (ASD) continues to grow in prevalence each passing year.
      As more children are diagnosed, it makes sense that the emerging adult and adult
      population with ASD also will continue to grow. Although the body of research is
      quite large for children with ASD, the literature for emerging adults with ASD is
      sparse in comparison. The current study aimed to extend existing literature
      further by beginning to explore the realm of emerging adulthood. Specifically,
      the study investigated the presence of comorbid psychiatric symptoms in emerging
      adults who also presented with ASD symptoms as measured by the Adult Self-Report
      (Rescorla and Achenbach in The Achenbach System of Empirically Based Assessment
      (ASEBA) for ages 18 to 90 years. The use of psychological testing for treatment
      planning and outcomes assessment: volume 3: instruments for adults, 3rd edn.
      Lawrence Erlbaum Associates, Mahwah, pp 115-152, 2004). Emerging adults were
      categorized as having normal, mild, moderate, or severe levels of ASD symptoms
      and were compared for the presence of comorbid psychiatric symptoms. Overall,
      results suggested that emerging adults who presented with greater ASD symptom
      severity were more likely to experience the presence of additional comorbid
      symptoms. 

PMID- 25995022
TI  - Enabling prominent high-rate and cycle performances in one lithium-sulfur
      battery: designing permselective gateways for Li(+) transportation in Holey-CNT/S
      cathodes.
AB  - A cathode material composed of h-CNT/S/ZrO2 is developed for lithium-sulfur
      batteries. By incorporating ZrO2 into the S-incorporated h-CNT, permselective
      gateways for free Li(+) transportation can be assembled at the mesopore openings,
      which deny the penetration of lithium polysulfides. At the ultrahigh rate of 10
      C, the discharge capacity averages to be 870 mA h g(-1) within 200 cycles. 

PMID- 25995023
TI  - 'Kids in the Kitchen' impact evaluation: engaging primary school students in
      preparing fruit and vegetables for their own consumption.
AB  - ISSUE ADDRESSED: Children's fruit and vegetable (FV) consumption in Australia is
      below levels recommended for optimal growth, development and health. METHODS:
      'Kids in the Kitchen' is a classroom-based program that engages students in
      preparing FV. Impact evaluation was conducted with students from Grade 1 (around
      6 years old) and Grade 5 (around 11 years old) who participated in the program. A
      questionnaire was used to collect pre- and post-program data on knowledge,
      attitudes and consumption of FV, FV preparation skills and environmental supports
      for FV consumption. A skill audit was also conducted for Grade 1 students.
      RESULTS: Study participants (n = 118) included 70 Grade 1 and 48 Grade 5
      students. There was an increase in the median number of fruits correctly
      identified (from 14 to 16), tried (from 14 to 16) and liked (from 10.5 to 12; P =
      0.0001 for all changes). The median number of vegetables correctly identified
      increased from 10 to 12 (P = 0.0001), but there was no change in the number of
      vegetables tried or liked. The proportion of participants who rated their skills
      in using a knife to prepare FV as 'not really that good' decreased by 15%, from
      42% to 27% (P = 0.04). Grade 1 participants' skills in cutting, grating and
      peeling improved (P = 0.0001 for all changes). CONCLUSIONS: If children are
      involved in the preparation of FV, they are more likely to correctly identify
      them, try them, like them and eat them. SO WHAT? Primary schools have the
      potential to contribute to children's nutrition through hands-on food preparation
      activities.

PMID- 25995024
TI  - Navigating the gender minefield: An IPV prevention campaign sheds light on the
      gender gap.
AB  - This article examines how differences in male and female views about intimate
      partner violence (IPV) contributed to divergent responses to a prevention
      campaign conducted in the western USA. The study examines focus groups (n = 22)
      and in-depth interview data (n = 13) collected during campaign development to
      shed light on quantitative results indicating that women (but not men) increased
      their perceived severity of domestic violence and awareness of services from pre
      test to post-test, while male attitudes moved in the opposite direction. Results
      of the qualitative study provide the basis for the authors' conclusions about why
      reactions differed: (1) men's unwillingness to view abuse within a gender context
      limits men's ability to accept the inequity in statistically demonstrated male
      and female roles as perpetrators and victims; (2) male resentment of existing
      gender stereotypes contributed to a rejection of campaign messages that utilised
      gender prevalence statistics to depict images showing men as perpetrators and
      women as victims; and (3) victim blaming attitudes contributed to resistance to
      empathy for victims depicted in the campaign. The authors offer suggestions for
      future campaigns that foster agency among both perpetrators and survivors while
      confronting the structural barriers to enacting change. 

PMID- 25995025
TI  - Corrigendum: The NCA sodium leak channel is required for persistent motor circuit
      activity that sustains locomotion.

PMID- 25995026
TI  - Non-vitamin K antagonist oral anticoagulants (NOACs) in the cardiac catherisation
      laboratory: Friends or Foes?

PMID- 25995027
TI  - [Endo- and ectoparasites of South American camelids and their control].
AB  - In a literature review, common endo- and ectoparasites of South American camelids
      are described, presenting morphological details and clinical signs important for
      diagnosis. Based on the life cycle of the parasites, possibilities for
      prophylaxis and therapy are indicated. The review should aid the veterinarian to
      diagnose and control common parasitic infections in South American camelids. 

PMID- 25995029
TI  - Investigation of Transcriptional Gene Profiling in Normal Murine Hair Follicular
      Substructures Using Next-Generation Sequencing to Provide Potential Insights Into
      Skin Disease.
AB  - Skin diseases, including hair-related diseases and neoplasia, are a major public
      health problem. While their prevalence is increasing, their treatment options are
      limited. Researchers have tried to investigate the genes and signal pathways
      underlying hair follicles (HFs) to develop genetically targeted therapies through
      microarrays, which represent an appropriate modality for the analysis of small
      genomes. To enable the comprehensive transcriptome analysis of large and/or
      complex transcriptomes, we performed RNA-seq using next-generation sequencing
      (NGS). We isolated interfollicular keratinocytes (IFKs), HFs, and dermal
      fibroblasts including dermal papilla cells (DFs-DPCs) from normal C57BL/6 murine
      skin, transplanted combinations of these samples into nude mice, and followed the
      mice over time. Sustained hair growth was supported by HFs and DFs-DPCs. We then
      investigated the pathways and the relevant gene ontology associated with any
      identified differentially expressed genes (DEGs). In addition, in the culture and
      flow cytometry (FCM), the HFs had a more quiescent cell cycle pattern than did
      the IFKs and DFs-DPCs. Therefore, the representative cell cycle-related gene
      expression of IFKs, HFs, and DFs-DPCs was analyzed by NGS. Our study will allow
      researchers to further investigate the potential interactions and signaling
      pathways that are active in HF-related diseases and cancer and may aid in future
      bioengineering applications. 

PMID- 25995028
TI  - Multi-omic profiling -of EPO-producing Chinese hamster ovary cell panel reveals
      metabolic adaptation to heterologous protein production.
AB  - Chinese hamster ovary (CHO) cells are the preferred production host for many
      therapeutic proteins. The production of heterologous proteins in CHO cells
      imposes a burden on the host cell metabolism and impact cellular physiology on a
      global scale. In this work, a multi-omics approach was applied to study the
      production of erythropoietin (EPO) in a panel of CHO-K1 cells under growth
      limited and unlimited conditions in batch and chemostat cultures. Physiological
      characterization of the EPO-producing cells included global transcriptome
      analysis, targeted metabolome analysis, including intracellular pools of
      glycolytic intermediates, NAD(P)H/NAD(P)(+) , adenine nucleotide phosphates
      (ANP), and extracellular concentrations of sugars, organic acids, and amino
      acids. Potential impact of EPO expression on the protein secretory pathway was
      assessed at multiple stages using quantitative PCR (qPCR), reverse transcription
      PCR (qRT-PCR), Western blots (WB), and global gene expression analysis to assess
      EPO gene copy numbers, EPO gene expression, intracellular EPO retention, and
      differentially expressed genes functionally related to secretory protein
      processing, respectively. We found no evidence supporting the existence of
      production bottlenecks in energy metabolism (i.e., glycolytic metabolites,
      NAD(P)H/NAD(P)(+) and ANPs) in batch culture or in the secretory protein
      production pathway (i.e., gene dosage, transcription and post-translational
      processing of EPO) in chemostat culture at specific productivities up to 5
      pg/cell/day. Time-course analysis of high- and low-producing clones in chemostat
      culture revealed rapid adaptation of transcription levels of amino acid catabolic
      genes in favor of EPO production within nine generations. Interestingly, the
      adaptation was followed by an increase in specific EPO productivity.

PMID- 25995030
TI  - [Not Available].

PMID- 25995031
TI  - [Not Available].

PMID- 25995032
TI  - Decreased expression of thymic stromal lymphopoietin in salivary glands of
      patients with primary Sjogren's syndrome is associated with increased disease
      activity.
AB  - OBJECTIVES: Thymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory
      cytokine involved in Th2- and Th17-mediated immune responses in different
      autoimmune diseases. TSLP expression in relation to disease activity was studied
      in salivary glands of primary Sjogren's syndrome (pSS) patients as compared to
      non-SS sicca (nSS) controls. METHODS: Tissue sections of minor salivary glands
      from pSS and nSS patients were stained with monoclonal antibodies against human
      TSLP, CD3, CD19 and cytokeratin high molecular weight (CK HMW) or stained for
      Alcian blue to detect mucus production. The number of TSLP-expressing cells was
      quantified and expression was correlated to local and systemic disease
      parameters. RESULTS: The number of TSLP-expressing cells was significantly lower
      in pSS patients than in nSS controls and correlated with a range of disease
      markers. In pSS patients, TSLP was expressed outside of lymphocytic infiltrates
      at sections that also encompassed high numbers of intact acinar cells. This
      difference was independent of tissue destruction. CONCLUSIONS: Reduced TSLP
      expression in pSS patients is associated with increased local and systemic
      inflammatory markers. Loss of TSLP expression may contribute to Th1/Th17
      associated immunopathology in pSS, in line with previous studies demonstrating
      that TSLP promotes a protective Th2 milieu at mucosal sites.

PMID- 25995033
TI  - SDF-1 and CXCR4 in synovium are associated with disease activity and bone and
      joint destruction in patients with rheumatoid arthritis treated with golimumab.
AB  - OBJECTIVES: The aim of this study was to determine whether the levels of stromal
      cell-derived factor (SDF)-1 and its receptor C-X-C chemokine receptor 4 (CXCR4)
      in synovium were correlated with clinical outcome and bone and joint destruction
      in rheumatoid arthritis (RA) patients being treated with golimumab. METHODS:
      Synovial tissues were obtained from 15 golimumab-treated patients and were
      assessed for SDF-1 and CXCR4 using a new immunohistological scoring system (IH
      score). The IH score was used to assess correlations between synovial SDF-1 or
      CXCR4 and the disease activity score (DAS28 CRP), Rooney score, tumor necrosis
      factor alpha, interleukin-6 (IL-6), CD4, CD20, CD68 and the Assessment of RA by
      Scoring of Large-Joint Destruction and Healing in Radiographic Imaging (ARASHI)
      score. Receiver-operating characteristic (ROC) curves were used to predict ARASHI
      scores from the CXCR4 IH scores. RESULTS: SDF-1 strongly correlated with the
      DAS28 CRP and serum IL-6. CXCR4 correlated with synovial CD4 and the ARASHI
      score. ROC analysis of CXCR4 and ARASHI scores >10 indicated a cutoff of 12
      points on the IH score for predicting joint destruction during treatment.
      CONCLUSIONS: Synovial SDF-1 correlated with disease activity, and its receptor
      CXCR4 was related to joint destruction in RA patients treated with golimumab.

PMID- 25995034
TI  - Deep-inspiration breath-hold 18F-FDG-PET/CT is useful for assessment of
      connective tissue disease associated interstitial pneumonia.
AB  - OBJECTIVE: To examine clinical utility of (18)F-flurodeoxyglucose (FDG)-positron
      emission tomography (PET)/CT for assessment of interstitial lung disease (ILD) in
      patients with connective tissue diseases (CTDs). METHODS: A total of 69 (18)F-FDG
      PET/CT scans were conducted under deep inspiratory breath hold (DIBH) conditions
      in 45 CTD patients with ILD, including 16 dermatomyositis/polymyositis, nine
      systemic scleroderma and seven rheumatoid arthritis. Intensity and distribution
      of (18)F-FDG signals in PET/CT were determined by standardized uptake value
      (SUVmax) and visual score in 18 regions, respectively. ILD was defined as active
      when immunosuppressive therapy was initiated or intensified. RESULTS: Both SUVmax
      and visual score were higher in active phase (n = 32) than inactive phase (n =
      37) (both p < 0.05), regardless of the underlying CTD and plain CT findings. The
      both parameters reduced after initiating or intensifying treatment in the follow
      up study of 17 active patients except two died patients who showed increased
      visual score. Another two died patients showed high visual score (15 and 6/18,
      respectively). Changing ratio of visual score, but not SUVmax was correlated with
      KL-6 (r(2) = 0.38, p < 0.05) and CRP (r(2) = 0.52, p < 0.05). CONCLUSION: The
      DIBH (18)F-FDG PET/CT procedure sensitively illustrates active ILD lesions in CTD
      and the extended signal distribution is associated with unfavorable clinical
      outcome.

PMID- 25995035
TI  - The embryonic Brachyury transcription factor is a novel biomarker of GIST
      aggressiveness and poor survival.
AB  - BACKGROUND: The T-box transcription factor Brachyury was recently reported to be
      upregulated and associated with prognosis in solid tumors. Here, we proposed to
      evaluate the potential use of Brachyury protein expression as a new prognostic
      biomarker in gastrointestinal stromal tumors (GIST). METHODS: Brachyury protein
      expression was analyzed by immunohistochemistry in a cohort of 63 bona fide GIST
      patients. Brachyury expression profiles were correlated with patients'
      clinicopathological features and prognostic impact. Additionally, an in silico
      analysis was performed using the Oncomine database to assess Brachyury
      alterations at DNA and mRNA levels in GISTs. RESULTS: We found that Brachyury was
      overexpressed in the majority (81.0 %) of primary GISTs. We observed Brachyury
      staining in the nucleus alone in 4.8 % of cases, 23.8 % depicted only cytoplasm
      staining, and 52.4 % of cases exhibited both nucleus and cytoplasm
      immunostaining. The presence of Brachyury was associated with aggressive GIST
      clinicopathological features. Particularly, Brachyury nuclear (with or without
      cytoplasm) staining was associated with the presence of metastasis, while
      cytoplasm sublocalization alone was correlated with poor patient survival.
      CONCLUSIONS: Herein, we demonstrate that Brachyury is overexpressed in GISTs and
      is associated with worse outcome, constituting a novel prognostic biomarker and a
      putative target for GIST treatment.

PMID- 25995036
TI  - Getting personal: Head and neck cancer management in the era of genomic medicine.
AB  - BACKGROUND: Genetic testing is rapidly becoming an important tool in the
      management of patients with head and neck cancer. As we enter the era of genomics
      and personalized medicine, providers should be aware of testing options,
      counseling resources, and the benefits, limitations, and future of personalized
      therapy. METHODS: This article offers a primer to assist clinicians treating
      patients in anticipating and managing the inherent practical and ethical
      challenges of cancer care in the genomic era. RESULTS: Clinical applications of
      genomics for head and neck cancer are emerging. We discuss the indications for
      genetic testing, types of testing available, implications for care,
      privacy/disclosure concerns, and ethical considerations. Hereditary genetic
      syndromes associated with head and neck neoplasms are reviewed, and online
      genetics resources are provided. CONCLUSION: This article summarizes and
      contextualizes the evolving diagnostic and therapeutic options that impact the
      care of patients with head and neck cancer in the genomic era. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E2250-E2258, 2016.

PMID- 25995038
TI  - Some recent developments in surface and interface design for photocatalytic and
      electrocatalytic hybrid structures.
AB  - The surface and interface are considered as the crucial features that can be
      engineered to improve the performance of catalysts. The great advancements in
      both controlled syntheses and catalytic mechanism studies have paved the way for
      the rational surface and interface design of catalysts. In this feature article,
      we overview our recent progress in surface and interface design for well-defined
      hybrid structures mainly toward the photocatalytic and electrocatalytic
      applications in which charge carriers play an important role. First, we outline
      the surface parameters of components including exposed facets, compositions,
      surface areas and crystal phases that have been tailored toward higher surface
      activation abilities for electrocatalytic and photocatalytic reactions. Second,
      we summarize the designing rules for the interface between two components to
      favor the charge transfer for photocatalytic reactions on the surface.
      Furthermore, we outline the synergistic effects on photocatalysis and
      electrocatalysis through the simultaneous control of the surface and the
      interface, which can also be extended to enhance other catalytic reactions (e.g.,
      CO oxidation). Finally, we discuss the challenges and opportunities for further
      development of surface and interface design toward catalytic performance tuning. 

PMID- 25995037
TI  - Comparing genetic counselor's and patient's perceptions of needs in prenatal
      chromosomal microarray testing.
AB  - OBJECTIVE: Chromosome microarray analysis is poised to take a significant place
      in the prenatal setting given its increased yield over standard karyotyping, but
      concerns regarding ethical and counseling challenges remain, especially
      associated with the risk of uncertain and incidental findings. Guidelines
      recommend patients receiving prenatal screening to undergo genetic counseling
      prior to testing, but little is known about women's specific pre-testing and post
      testing informational needs, as well as their preference for return of various
      types of results. METHODS: The present study surveys 199 prenatal genetic
      counselors who have counseled patients undergoing chromosome microarray analysis
      testing and 152 women who have undergone testing on the importance of
      understanding pre-test information, return of various types of results, and
      resources made available following an abnormal finding. RESULTS: Counselors and
      patients agree on many aspects, although findings indicate patients consider all
      available information very important, while genetic counselors give more varying
      ratings. CONCLUSION: Counseling sessions would benefit from information
      personalized to a patient's particular needs and a shared decision-making model,
      to reduce informational overload and avoid unnecessary anxiety. Additionally,
      policies regarding the return of various types of results are needed. (c) 2015
      John Wiley & Sons, Ltd.

PMID- 25995039
TI  - Differential Immune Responses and Protective Effects in Avirulent Mycobacterial
      Strains Vaccinated BALB/c Mice.
AB  - Screening live mycobacterial vaccine candidates is the important strategy to
      develop new vaccines against adult tuberculosis (TB). In this study, the
      immunogenicity and protective efficacy of several avirulent mycobacterial strains
      including Mycobacterium smegmatis, M. vaccae, M. terrae, M. phlei, M. trivial,
      and M. tuberculosis H37Ra were compared with M. bovis BCG in BALB/c mice. Our
      results demonstrated that differential immune responses were induced in different
      mycobacterial species vaccinated mice. As BCG-vaccinated mice did, M. terrae
      immunization resulted in Th1-type responses in the lung, as well as splenocytes
      secreting IFN-gamma against a highly conserved mycobacterial antigen Ag85A. M.
      smegmatis also induced the same splenocytes secreting IFN-gamma as BCG and M.
      terrae did. In addition, M. terrae and M. smegmatis-immunized mice predominantly
      increased expression of IL-10 and TGF-beta in the lung. Most importantly, mice
      vaccinated with H37Ra and M. vaccae could provide the same protection in the lung
      against virulent M. tuberculosis challenge as BCG. The result may have important
      implications in developing adult TB vaccine. 

PMID- 25995041
TI  - Open Source Bayesian Models. 2. Mining a "Big Dataset" To Create and Validate
      Models with ChEMBL.
AB  - In an associated paper, we have described a reference implementation of Laplacian
      corrected naive Bayesian model building using extended connectivity (ECFP)- and
      molecular function class fingerprints of maximum diameter 6 (FCFP)-type
      fingerprints. As a follow-up, we have now undertaken a large-scale validation
      study in order to ensure that the technique generalizes to a broad variety of
      drug discovery datasets. To achieve this, we have used the ChEMBL (version 20)
      database and split it into more than 2000 separate datasets, each of which
      consists of compounds and measurements with the same target and activity
      measurement. In order to test these datasets with the two-state Bayesian
      classification, we developed an automated algorithm for detecting a suitable
      threshold for active/inactive designation, which we applied to all collections.
      With these datasets, we were able to establish that our Bayesian model
      implementation is effective for the large majority of cases, and we were able to
      quantify the impact of fingerprint folding on the receiver operator curve cross
      validation metrics. We were also able to study the impact that the choice of
      training/testing set partitioning has on the resulting recall rates. The datasets
      have been made publicly available to be downloaded, along with the corresponding
      model data files, which can be used in conjunction with the CDK and several
      mobile apps. We have also explored some novel visualization methods which
      leverage the structural origins of the ECFP/FCFP fingerprints to attribute
      regions of a molecule responsible for positive and negative contributions to
      activity. The ability to score molecules across thousands of relevant datasets
      across organisms also may help to access desirable and undesirable off-target
      effects as well as suggest potential targets for compounds derived from
      phenotypic screens. 

PMID- 25995040
TI  - Prolonged overexpression of Wnt10b induces epidermal keratinocyte transformation
      through activating EGF pathway.
AB  - Wnt10b is a signaling protein regulating skin development and homeostasis, and
      the expression of Wnt10b is restricted to epidermal keratinocytes in embryonic
      and postnatal skin. Recent studies indicate an elevated expression of Wnt10b in
      skin tumors. However, how Wnt10b regulates skin tumorigenesis remains largely
      unknown. Here we report that continuous expression of Wnt10b mediates
      transformation of epidermal keratinocytes through activating genes involved in
      EGF/MAPK signaling pathways. We first established a prolonged Wnt10b
      overexpression system in JB6P- cells to represent the elevated Wnt10b expression
      level in skin keratinocytes. Through expression assays and observations under
      phase-contrast microscopy, prolonged expression of Wnt10b activated Wnt/beta
      catenin pathway and induced morphological changes of cells showing longer
      protrusions and multilayer growth, indicating early-stage cell transformation.
      Wnt10b also increased cellular proliferation and migration according to BrdU
      incorporation and cell mobility assays. Furthermore, multi-doses of AdWnt10b
      treatment to JB6P- cells induced colony formation, stronger invasive ability in
      transwell system, and anchorage-independent growth in agar gel. In molecular
      level, AdWnt10b treatment induced increased transcriptional expressions of Egf,
      downstream Mapk pathway factors, and MMPs. Administration of Wnt antagonist DKK1
      blocked the tumor promotion process induced by Wnt10b. Taken together, these
      findings clearly demonstrate that Wnt10b promotes epidermal keratinocyte
      transformation through induced Egf pathway. 

PMID- 25995042
TI  - PHACTR1: Functional Clues Linking a Genome-Wide Association Study Locus to
      Coronary Artery Disease.

PMID- 25995043
TI  - Circulating MicroRNAs Link Inflammation to Impaired Wound Healing in Diabetes.

PMID- 25995045
TI  - Correction.

PMID- 25995044
TI  - The growing problem of obesity: mechanisms, consequences, and therapeutic
      approaches.

PMID- 25995046
TI  - Inhibitory effect of super-hydrophobicity on silver release and antibacterial
      properties of super-hydrophobic Ag/TiO2 nanotubes.
AB  - The antibacterial properties of super-hydrophobic silver (Ag) on implant surface
      have not yet to be fully illuminated. In our study, we investigate the protective
      effects of super-hydrophobic coating of silver/titanium dioxide (Ag/TiO2 )
      nanotubes against bacterial pathogens, as well as its pattern of Ag release.
      Ag/TiO2 nanotubes are prepared by a combination of electrochemical anodization
      and pulse electrodeposition. The super-hydrophobic coating is prepared by
      modifying the surface of Ag/TiO2 nanotubes with 1H, 1H, 2H, 2H-perfluorooctyl
      triethoxysilane (PTES). Surface features and Ag release are examined by SEM, X
      ray photoelectron spectroscopy, contact-angle measurement, and inductively
      coupled plasma-mass spectrometry (ICP-MS). The antibacterial activity of super
      hydrophobic coating Ag/TiO2 nanotubes is investigated both in vitro and in vivo.
      Consequently, the super-hydrophobic coating on Ag/TiO2 nanotubes shows a
      regularly arranged structure; and nano-Ag particles (10-30 nm) are evenly
      distributed on the surface or inside the nanotubes. The contact angles of water
      on the super-hydrophobic coating Ag/TiO2 nanotubes are all above 150 degrees . In
      addition, the super-hydrophobic character displays a certain conserved effect
      that contributes to the sustained release of Ag. The super-hydrophobic Ag/TiO2
      nanotubes are also effective in inhibiting bacterial adhesion, killing the
      adhering bacteria and preventing postoperative infection in rabbits. Therefore,
      it is expected that the super-hydrophobic Ag/TiO2 nanotubes which can contain the
      release of Ag, leading to stable release, may show a consistent surface
      antibacterial capability. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 104B: 1004-1012, 2016.

PMID- 25995047
TI  - Emotion Regulation Moderates the Association Between Proximal Negative Affect and
      Intimate Partner Violence Perpetration.
AB  - Negative affect is a central component of many theories of aggressive behavior.
      Though understudied, it is likely that proximal negative affect increases the
      odds of aggression perpetration when individuals have poor emotion regulation,
      but not when individuals have more adaptive emotion regulation. Thus, the current
      study examined (1) the proximal effect of various indicators of negative affect
      (e.g., anger, hostility, depression) on intimate partner violence (IPV)
      perpetration and (2) whether poor emotion regulation moderated these
      associations. For up to 90 consecutive days, male college students (N = 67) in a
      current dating relationship completed daily surveys on their negative affect and
      IPV perpetration. Results demonstrated that emotion regulation moderated many of
      the associations between proximal negative affect and physical aggression
      perpetration, such that negative affect was associated with increased odds of
      violence when poor emotion regulation was high but not low. This is the first
      study to demonstrate the moderating role of emotion regulation in the link
      between proximal negative affect and IPV perpetration. As such, these findings
      have important implications for existing theories of IPV and emotion regulation
      and suggest that interventions may effectively reduce IPV by targeting emotion
      regulation.

PMID- 25995048
TI  - Topical application of a novel oxycodone gel formulation (tocopheryl phosphate
      mixture) in a rat model of peripheral inflammatory pain produces localized pain
      relief without significant systemic exposure.
AB  - This study was designed to assess the analgesic efficacy and systemic exposure of
      oxycodone administered topically in a novel tocopheryl phosphate mixture (TPM)
      gel formulation, to the inflamed hindpaws in a rat model of inflammatory pain.
      Unilateral hindpaw inflammation was induced in male Sprague-Dawley rats by
      intraplantar (i.pl.) injection of Freund's complete adjuvant (FCA). Mechanical
      hyperalgesia and hindpaw inflammation were assessed by measuring paw pressure
      thresholds and hindpaw volume, respectively, just prior to i.pl. FCA and again 5
      6 days later. The analgesic effects of oxycodone administered topically (1 mg in
      TPM gel) or by i.pl. injection (50 MUg), were assessed. Systemic oxycodone
      exposure was assessed over an 8-h postdosing interval following topical
      application. Skin permeation of oxycodone from the gel formulation was assessed
      in vitro using Franz diffusion cells. Oxycodone administered topically or by
      i.pl. injection produced significant (p < 0.05) analgesia in the inflamed
      hindpaws. Systemic oxycodone exposure was insignificant after topical dosing. The
      in vitro cumulative skin permeation of oxycodone was linearly related to the
      amount applied. Topical TPM/oxycodone gel formulations have the potential to
      alleviate moderate to severe inflammatory pain conditions with minimal systemic
      exposure, thereby avoiding central nervous system (CNS)-mediated adverse effects
      associated with oral administration of opioid analgesics.

PMID- 25995049
TI  - Dishware size and snack food intake in a between-subjects laboratory experiment.
AB  - OBJECTIVE: The use of smaller dishware as a way of reducing food consumption has
      intuitive appeal and is recommended to the general public. Recent experimental
      studies have failed to find an effect of plate size on food intake, although the
      methods used across studies have varied. The aim of the present study was to
      examine the effect that bowl size had on snack food consumption in a 'typical'
      snacking context (snacking while watching television). DESIGN: Between-subjects.
      SETTING: Laboratory experiment. SUBJECTS: Sixty-one adult participants served
      themselves and ate popcorn while watching television. Participants were randomly
      assigned to serve themselves with and eat from either a small or a large bowl.
      RESULTS: The use of a smaller bowl size did not reduce food consumption.
      Unexpectedly, participants in the small bowl condition tended to consume more
      popcorn (34.0 g) than participants in the large bowl condition (24.9 g; 37 %
      increase, d=0.5), although the statistical significance of this difference
      depended on whether analyses were adjusted to account for participant
      characteristics (e.g. gender) associated with food intake (P=0.02) or not
      (P=0.07). CONCLUSIONS: Counter to widely held belief, the use of a smaller bowl
      did not reduce snack food intake. Public health recommendations advising the use
      of smaller dishware to reduce food consumption are premature, as this strategy
      may not be effective.

PMID- 25995050
TI  - Two Indian states promise to enforce act that punishes violent attacks against
      doctors.

PMID- 25995051
TI  - The Influence of Rehabilitative and Punishment Ideology on Correctional Officers'
      Perceptions of Informal Bases of Power.
AB  - Maintaining order is a key goal for prison managers. Much of the research on
      order maintenance focuses, however, on disruptions of order, even when order is
      more common. Examining factors related to perceptions on how officers get inmates
      to comply is, therefore, an important consideration. Using a survey of
      correctional officers from a Mid-Atlantic state, this study considers three
      dimensions of French and Raven's theory on the bases of power. The focus is to
      examine correctional orientation and compliance regarding three dimensions of
      power that rely on informal control and relationships. The results indicate that
      officers' belief in rehabilitative ideals is consistently related to the
      dimensions of legitimate, referent, and expert control. Other individual and
      organizational factors are also related to dimensions of power. Implications for
      policies and for future research are discussed. 

PMID- 25995052
TI  - Accountability in Juvenile Justice: A Framework to Assess Client Outcomes.
AB  - This article describes the development of an assessment protocol for use with
      juvenile justice clients that can be used to assess needs in a manner that not
      only informs the development of case plans but also allows for the assessment of
      change over the course of a service contact. The youth justice assessment tool
      supports case needs identification and analysis as well as screening for mental
      health concerns, risk of harm to self or others, and risk of reoffending. Initial
      validation of the case needs component has been undertaken and although further
      validation is required, preliminary data reported in this article suggest that
      this type of approach to client assessment does hold some promise. 

PMID- 25995054
TI  - Cost-effectiveness of Babesia microti antibody and nucleic acid blood donation
      screening using results from prospective investigational studies.
AB  - BACKGROUND: Babesia microti causes transfusion-transmitted babesiosis (TTB);
      currently, blood donor screening assays are unlicensed but used
      investigationally. STUDY DESIGN AND METHODS: We developed a decision tree model
      assessing the comparative- and cost-effectiveness of B. microti blood donation
      screening strategies in endemic areas compared to the status quo (question
      regarding a history of babesiosis), including testing by: (1) universal antibody
      (Ab), (2) universal polymerase chain reaction (PCR), (3) universal Ab/PCR, and
      (4) recipient risk-targeted Ab/PCR. The model predicted the number of TTB cases,
      complicated TTB cases, cases averted, and quality-adjusted life years (QALYs).
      Economic outcomes included each strategy's per-donation cost, waste (number of
      infection-free units incorrectly discarded), and waste index (number wasted
      units/number true positives). Sensitivity analyses examined uncertainty in
      transmission probabilities, prevalence rates, and other key model inputs.
      RESULTS: Universal PCR in four endemic states would prevent 24 to 31 TTB
      cases/100,000 units transfused (pht) at an incremental cost-effectiveness ratio
      (ICER) of $26,000 to $44,000/QALY (transmission probability dependent) and waste
      index of zero. Universal Ab/PCR would prevent 33 to 42 TTB cases pht at an ICER
      of $54,000 to $83,000/QALY and waste index of 0.05. The questionnaire is most
      wasteful (99.62 units wasted pht; 208.62 waste index), followed by the risk
      targeted strategy (76.27 units wasted pht; 0.68 waste index). The model predicted
      zero cases of TTB or complicated TTB with universal Ab/PCR (versus [33, 42] and
      [13, 18] pht, respectively [no screening]). Results are highly sensitive to
      transmission probabilities. CONCLUSIONS: Universal PCR in endemic states is an
      effective blood donation screening strategy at a threshold of $50,000/QALY. Using
      a higher cost-effectiveness ratio, universal Ab/PCR is the most effective
      strategy.

PMID- 25995053
TI  - A Novel Mechanism of Spine Damages in Stroke via DAPK1 and Tau.
AB  - Synaptic spine loss is one of the major preceding consequences of stroke damages,
      but its underlying molecular mechanisms remain unknown. Here, we report that a
      direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal
      death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau
      protein at Ser262 (pS(262)) in cortical neurons of stroke mice. Either genetic
      deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD(-/-)) or blocking DAPK1
      Tau interaction by systematic application of a membrane permeable peptide
      protects spine damages and improves neurological functions against stroke
      insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in
      clinical management of stroke. 

PMID- 25995055
TI  - Quality of life in idiopathic intracranial hypertension at diagnosis: IIH
      Treatment Trial results.
AB  - OBJECTIVE: The study purpose was to examine vision-specific and overall health
      related quality of life (QOL) at baseline in Idiopathic Intracranial Hypertension
      Treatment Trial patients who were newly diagnosed and had mild visual loss. We
      also sought to determine the associations between vision-specific QOL scores and
      visual symptoms, visual function, pain, headache-related disability, and obesity.
      METHODS: We assessed QOL using the 36-Item Short Form Health Survey, National Eye
      Institute Visual Function Questionnaire-25 (NEI-VFQ-25), and 10-Item NEI-VFQ-25
      Neuro-Ophthalmic Supplement. We compared these results with those of previously
      reported idiopathic intracranial hypertension (IIH) QOL studies. We assessed
      relationships between QOL and other clinical characteristics. RESULTS: Among 165
      participants with IIH (161 women and 4 men with a mean age +/- SD of 29.2 +/- 7.5
      years), vision-specific QOL scores were reduced compared with published values
      for disease-free controls. Scores of participants were comparable to published
      results for patients with multiple sclerosis and a history of optic neuritis. A
      multiple linear regression model for the NEI-VFQ-25 composite score found that
      perimetric mean deviation in the best eye, visual acuity in the worst eye, visual
      symptoms, and pain symptoms (headache, neck pain), but not obesity, were
      independently associated with QOL. CONCLUSIONS: IIH affects QOL at time of
      diagnosis even in patients with mild visual impairment. Vision-specific QOL in
      patients with newly diagnosed IIH may be as decreased as that for patients with
      other neuro-ophthalmic disorders. IIH treatment should target visual loss and
      other symptoms of increased intracranial pressure associated with reduced QOL.
      Reduced QOL does not simply reflect obesity, an underlying IIH risk factor.

PMID- 25995056
TI  - Depression and subsequent risk of Parkinson disease: A nationwide cohort study.
AB  - OBJECTIVE: To investigate the long-term risk of Parkinson disease (PD) after
      depression and evaluate potential confounding by shared susceptibility to the 2
      diagnoses. METHODS: The nationwide study cohort included 140,688 cases of
      depression, matched 1:3 using a nested case-control design to evaluate temporal
      aspects of study parameters (total, n = 562,631). Potential familial
      coaggregation of the 2 diagnoses was investigated in a subcohort of 540,811
      sibling pairs. Associations were investigated using multivariable adjusted
      statistical models. RESULTS: During a median follow-up period of 6.8 (range, 0
      26.0) years, 3,260 individuals in the cohort were diagnosed with PD. The
      multivariable adjusted odds ratio (OR) for PD was 3.2 (95% confidence interval
      [CI], 2.5-4.1) within the first year of depression, decreasing to 1.5 (95% CI,
      1.1-2.0) after 15 to 25 years. Among participants with depression, recurrent
      hospitalization was an independent risk factor for PD (OR, 1.4; 95% CI, 1.1-1.9
      for >=5 vs 1 hospitalization). In family analyses, siblings' depression was not
      significantly associated with PD risk in index persons (OR, 1.1; 95% CI, 0.9
      1.4). CONCLUSIONS: The time-dependent effect, dose-response pattern for recurrent
      depression, and lack of evidence for coaggregation among siblings all indicate a
      direct association between depression and subsequent PD. Given that the
      association was significant for a follow-up period of more than 2 decades,
      depression may be a very early prodromal symptom of PD, or a causal risk factor.

PMID- 25995058
TI  - Influence of ethnicity on response to asthma drugs.
AB  - INTRODUCTION: Understanding variability in the response to asthma medications is
      essential to ensure appropriate prescribing. Given that there are increased
      asthma treatment failures observed in ethnic minorities receiving asthma
      therapeutics, it is fundamental to understand the factors related to ethnicity
      that can modify the response to asthma therapy. AREAS COVERED: Race/ethnicity is
      an important determinant of drug response and therefore contributes to
      interindividual variability. It is generally recognized that its effects on drug
      response are determined by both genetic and environmental factors to a varying
      extent, depending on the ethnic groups and probe drugs studied. Also, adherence
      to therapy can influence pharmacological response to asthma therapeutics. EXPERT
      OPINION: Health-care professionals might never use the treatment in their
      patients irrespective of their ethnicity and thus inadvertently increase ethnic
      health inequality. However, our understanding of whether and/or how ethnicity
      influences pharmacological response to asthma therapeutics is still very scarce.
      A holistic, integrative systems biology approach that combines large-scale
      molecular profiling traits (e.g., transcriptomic, proteomic, metabolomic traits)
      and genetic variants could help to personalize the treatment of asthmatic
      patients regardless of race/ethnicity.

PMID- 25995059
TI  - Audible air leak during labor epidural analgesia.

PMID- 25995057
TI  - Feasibility and Effectiveness of a Multi-Element Psychosocial Intervention for
      First-Episode Psychosis: Results From the Cluster-Randomized Controlled GET UP
      PIANO Trial in a Catchment Area of 10 Million Inhabitants.
AB  - Integrated multi-element psychosocial interventions have been suggested to
      improve the outcomes of first-episode psychosis (FEP) patients, but they have
      been studied primarily in experimental settings and in nonepidemiologically
      representative samples. Thus, we performed a cluster-randomized controlled trial,
      comparing an integrated multi-element psychosocial intervention, comprising
      cognitive behavioral therapy, family intervention, and case management, with
      treatment as usual (TAU) for FEP patients in 117 community mental health centers
      (CMHCs) in a large area of northern Italy (10 million inhabitants). The
      randomized units (clusters) were the CMHCs, and the units of observation the
      patients (and, when available, their family members). The primary hypotheses were
      that add-on multicomponent intervention: (1) results in greater improvements in
      symptoms, as assessed with positive and negative syndrome scale and (2) reduces
      in-hospital stay, based on days of hospitalization over the 9-month follow-up.
      Four hundred and forty-four FEP patients received the intervention or TAU and
      were assessed at baseline and 9 months. Based on the retention rates of patients
      (and families) in the experimental arm, multi-element psychosocial interventions
      can be implemented in routine mental health services. Regarding primary outcomes,
      patients in the experimental arm showed greater reductions in overall symptom
      severity, while no difference could be found for days of hospitalization. Among
      the secondary outcomes, greater improvements were detected in the experimental
      arm for global functioning, emotional well-being, and subjective burden of
      delusions. No difference could be found for service disengagement and subjective
      burden of auditory hallucinations. These findings support feasibility and
      effectiveness of early interventions for psychosis in generalist mental health
      services. 

PMID- 25995060
TI  - Effects of levobupivacaine on isolated rat tracheal smooth muscle.
AB  - Levobupivacaine has been developed as a safer alternative to bupivacaine because
      of its reduced systemic toxicity. However, the effect of directly delivering
      levobupivacaine into tracheal smooth muscle has not been adequately explored. We
      performed this study to determine the in vitro effects of levobupivacaine on
      isolated rat tracheal smooth muscle. A portion of rat trachea 5 mm in length was
      mounted in 30 ml of Krebs solution in a muscle bath at 37  degrees C. The
      following effects of levobupivacaine were assessed: (1) the effect on tracheal
      smooth muscle resting tension (n = 6), (2) the effect on contraction caused by
      10(-6) M methacholine (n = 6) and (3) the effect on electrically induced tracheal
      smooth muscle contractions (n = 6). Levobupivacaine caused dose-dependent
      relaxation in the trachealis muscle precontracted with 10(-6) M methacholine.
      Contraction inhibition was statistically significant when 10(-5) and 10(-4) M
      levobupivacaine were applied, compared with the contraction inhibition that
      occurred in the control groups (p < 0.01). A high dose of levobupivacaine also
      decreased the spike contraction induced by electrical field stimulation. This
      study indicated that high concentrations of levobupivacaine might antagonize the
      cholinergic receptors and inhibit parasympathetic function of the trachea.

PMID- 25995061
TI  - Preoperative anxiety induces no clinically relevant effect on intraoperative
      nociceptive levels during breast surgery under general anesthesia.
AB  - Anxiety can affect acute and chronic postoperative pain after breast surgery.
      Nociceptive response during surgery might also be affected by preoperative
      anxiety even under unconscious state during general anesthesia. The aim of this
      retrospective study was to investigate nociceptive responses during breast
      surgery under general anesthesia in patients with or without preoperative
      anxiety. Patients (n = 45) were divided into a low-anxiety group (n = 25) and a
      high-anxiety group (n = 20) in accordance with preoperative scores for the State
      Trait Anxiety Inventory. We performed discriminant analysis to compare
      nociception during surgery using three intraoperative averaged values: heart
      rate; systolic blood pressure; and perfusion index. No significant differences in
      discriminant score were seen between groups (p = 0.10). Although we performed
      propensity score-matching to reduce the bias due to confounding variables in this
      retrospective study, there was also no significant difference in levels of
      nociceptive response between groups (p = 0.06). In conclusion, the level of
      nociception during breast surgery is not significantly affected by preoperative
      anxiety.

PMID- 25995062
TI  - Magnetization Reversal by Out-of-plane Voltage in BiFeO3-based Multiferroic
      Heterostructures.
AB  - Voltage controlled 180 degrees  magnetization reversal has been achieved in
      BiFeO3-based multiferroic heterostructures, which is promising for the future
      development of low-power spintronic devices. However, all existing reports
      involve the use of an in-plane voltage that is unfavorable for practical device
      applications. Here, we investigate, using phase-field simulations, the out-of
      plane (i.e., perpendicular to heterostructures) voltage controlled magnetism in
      heterostructures consisting of CoFe nanodots and (110) BiFeO3 thin film or
      island. It is predicted that the in-plane component of the canted magnetic moment
      at the CoFe/BiFeO3 interface can be reversed repeatedly by applying a
      perpendicular voltage across the bottom (110) BiFeO3 thin film, which further
      leads to an in-plane magnetization reversal in the overlaying CoFe nanodot. The
      non-volatility of such perpendicular voltage controlled magnetization reversal
      can be achieved by etching the continuous BiFeO3 film into isolated nanoislands
      with the same in-plane sizes as the CoFe nanodot. The findings would provide
      general guidelines for future experimental and engineering efforts on developing
      the electric-field controlled spintronic devices with BiFeO3-based multiferroic
      heterostructures. 

PMID- 25995064
TI  - Shisha smoking: An emerging trend in Southeast  Asian nations.
AB  - Shisha smoking, with origins in India and the Arab world, is today spreading
      rapidly into other parts of the world. One such region is Southeast Asia,where
      shisha bars are commonly seen around educational institutions. The general public
      remains unaware of the harmful effects of shisha smoking and many assume that
      shisha smoking does not involve tobacco. Shisha smoking is not adequately
      addressed in the current anti-tobacco policies by most governments of Southeast
      Asia. Only a few countries have already taken concrete measures of including
      shisha smoking in anti-tobacco policies. We highlight the emerging trend of
      shisha smoking in Southeast Asian nations, associated health effects, and the
      loopholes in the governmental policies that are being exploited by the vendors of
      shisha. While most research, taxation policies, and health education on tobacco
      related products have focused on cigarettes, additional methods of tobacco
      delivery become more common.

PMID- 25995065
TI  - The Root of Flowering Plants and Total Evidence.
AB  - Support for Amborella as the sole survivor of an evolutionary lineage that is
      sister to all other angiosperms comes from positions in DNA multiple-sequence
      alignments that have a poor fit to time-reversible substitution models. These
      sites exhibit significant levels of homoplasy, compositional heterogeneity, and
      strong heterotachy. We report phylogenetic analyses with observed, randomized,
      and simulated data which show there is little or no expectation that these sites
      provide useful information for understanding relationships among basal
      angiosperms. Their inclusion in phylogenetic analyses leads to a long-branch
      attraction artifact that favors Amborella as sister to other angiosperms in
      reconstructed phylogenies. Using parametric simulations, we show that sites in
      chloroplast sequences that exhibit less homoplasy between angiosperms and
      gymnosperms provide more reliable information for inferring basal angiosperm
      relationships. We confirm our earlier findings that the basal angiosperm
      Amborella is most closely related to aquatic herbs. Our current and previously
      reported (Goremykin et al. 2013) analyses highlight an essential aspect of the
      total evidence approach to phylogenetic inference. They suggest that data
      partitioning aimed at identifying components of the data that better fit
      evolutionary models is a more reliable approach to phylogeny reconstruction at
      deep taxonomic levels. 

PMID- 25995066
TI  - Remodeling changes of the upper airway with chronic rhinosinusitis.
AB  - BACKGROUND: Although remodeling changes of the lower airway are well described,
      similar changes in the upper airway are less well known. Remodeling changes of
      the upper airway in chronic rhinosinusitis (CRS) relevant to different phenotypes
      and endotypes and their clinical characteristics are investigated. METHODS: A
      cross-sectional study of adult patients with CRS was performed. Mucosal samples
      were taken during endoscopic sinus surgery (ESS). Histopathological analysis
      included eosinophil count, eosinophil activation (eosinophilic mucin), and
      remodeling changes. Mucosal damage was defined as ulceration, edema, and
      hypertrophic changes. Patient-reported outcomes (PROMs) were assessed using a
      Nasal Symptom Score (NSS) and Sino-Nasal Outcome Test (SNOT-22). Patients were
      subgrouped by presence of polyps (CRSwNP/CRSsNP) or tissue eosinophilia (>10/high
      power field). Subgroup analysis was performed when both eosinophilic chronic
      rhinosinusitis (eCRS) and eosinophil activation (eCRSwEA) were coexistent.
      Analysis between subgroups, pathology, and PROMs was also performed. RESULTS: A
      total of 259 patients (age 48.5 +/- 15.6 years, 45% female) were recruited; 53%
      CRSwNP, 51% eCRS. Remodeling changes were present in 85%, higher in both CRSwNP
      (90%, p = 0.006) and eCRS (91%, p = 0.004). Mucosal damage changes were common in
      eCRS (ulceration 18%, p = 0.003; edema 98%, p < 0.001; hypertrophic changes 25%,
      p = 0.007). NSS was worse in CRSwNP compared to CRSsNP (2.84 +/- 1.1 vs 2.29 +/-
      1.1, p < 0.001) and eCRSwEA (2.95 +/- 0.16 vs 2.51 +/- 0.11, p = 0.04). "Loss of
      sense of smell or taste" was worse in patients with evidence of mucosal damage (p
      = 0.006). CONCLUSION: Remodeling features are present in CRS. Tissue eosinophilia
      and evidence of eosinophil activation is closely associated with remodeling
      features of CRS, associated mucosal damage and clinical symptoms.

PMID- 25995067
TI  - Cloning and characterization of calreticulin and its association with salinity
      stress in P. trituberculatus.
AB  - Calreticulin (CRT) is a highly conserved and multifunctional endoplasmic
      reticulum (ER) chaperone protein and plays important roles in salinity stress
      response. Portunus trituberculatus is a commercially important fishery species,
      and water salinity conditions influence its commercial farming significantly. In
      order to research the function of calreticulin under salinity stress, the full
      length cDNA sequence of calreticulin from P. trituberculatus (PtCRT) was firstly
      cloned and characterized. The complete cDNA sequence of PtCRT is 1676 bp with
      1218 bp open reading frame (ORF), encoding a polypeptide of 405 amino acids.
      Multiple sequence alignments showed that the deduced acid amino sequences of
      PtCRT shared the highest homology to CRT of Fenneropenaeus chinensis (89%).
      Fluorescent quantitative real-time PCR analysis indicated that PtCRT was
      expressed in all detected tissues and showed the highest expression level in
      hepatopancreas. In addition, salinity challenge significantly influenced the
      expression level of PtCRT in gill. Six single nucleotide polymorphisms (SNPs)
      were detected in cDNA sequence of PtCRT, and one SNP was associated with the salt
      tolerant trait. All results indicated that PtCRT plays an important role in
      mediating the salinity adaption of P. trituberculatus.

PMID- 25995068
TI  - Exploring the interplay between the motivational climate and goal orientation in
      predicting maximal oxygen uptake.
AB  - Drawing upon achievement goal theory, this study explored the interplay between
      the perceived motivational climate, achievement goals and objective measurements
      of maximal oxygen uptake (VO2max). The results of a study of 123 individuals from
      three Norwegian military academies revealed that under the condition of a high
      performance orientation there is a stronger positive relationship between
      performance climate and VO2max for individuals reporting a low (rather than high)
      mastery orientation. Furthermore, we found that for individuals with a high
      mastery orientation there is a stronger positive relationship between mastery
      climate and VO2max for individuals reporting a low (rather than high)-performance
      orientation. These findings contribute to achievement goal theory by providing
      support for an interactionist person-environment fit perspective. Implications
      for future research and practice are discussed. 

PMID- 25995069
TI  - Pricing of pneumococcal conjugate vaccine challenged.

PMID- 25995070
TI  - COPD staging with GOLD: the newer the better?

PMID- 25995071
TI  - Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD
      2007 and 2011 staging systems: a pooled analysis of individual patient data.
AB  - BACKGROUND: There is no universal consensus on the best staging system for
      chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global
      Initiative for Chronic Obstructive Lung Disease [GOLD] 2007) have traditionally
      used forced expiratory volume in 1 s (FEV1) for staging, clinical parameters have
      been added to some guidelines (eg, GOLD 2011) to improve patient management. As
      part of the COPD Cohorts Collaborative International Assessment (3CIA)
      initiative, we aimed to investigate how individual patients were categorised by
      GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents
      for mortality. METHODS: We searched reports published from Jan 1, 2008, to Dec
      31, 2014. Using data from cohorts that agreed to participate and had a minimum
      amount of information needed for GOLD 2007 and 2011, we did a patient-based
      pooled analysis of existing data. With use of raw data, we recalculated all
      participant assignments to GOLD 2007 I-IV classes, and GOLD 2011 A-D stages. We
      used survival analysis, C statistics, and non-parametric regression to model time
      to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict
      mortality. FINDINGS: We collected individual data for 15 632 patients from 22
      COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the
      patients was 63.9 years (SD 10.1); 10 751 (69%) were men. Based on FEV1 alone
      (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346
      (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging
      with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660
      patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade
      C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity
      distribution to more severe categories. There were nearly three times more COPD
      patients in stage D than in former stage IV (p<0.05). The predictive capacity for
      survival up to 10 years was significant for both systems (p<0.01) but area under
      the curves were only 0.623 (GOLD 2007) and 0.634 (GOLD 2011), and GOLD 2007 and
      2011 did not differ significantly. We identified the percent predicted FEV1
      thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality,
      which are similar to the ones used previously. INTERPRETATION: Neither GOLD COPD
      classification schemes have sufficient discriminatory power to be used clinically
      for risk classification at the individual level to predict total mortality for 3
      years of follow-up and onwards. Increasing intensity of treatment of patients
      with COPD due to their GOLD 2011 reclassification is not known to improve health
      outcomes. Evidence-based thresholds should be searched when exploring the
      prognostic ability of current and new COPD multicomponent indices. FUNDING: None.

PMID- 25995072
TI  - Mode-matching metasurfaces: coherent reconstruction and multiplexing of surface
      waves.
AB  - Metasurfaces are promising two-dimensional metamaterials that are engineered to
      provide unique properties or functionalities absent in naturally occurring
      homogeneous surfaces. Here, we report a type of metasurface for tailored
      reconstruction of surface plasmon waves from light. The design is based on an
      array of slit antennas arranged in a way that it matches the complex field
      distribution of the desired surface plasmon wave. The approach is generic so that
      one can readily create more intricate designs that selectively generate different
      surface plasmon waves through simple variation of the wavelength or the
      polarization state of incident light. The ultra-thin metasurface demonstrated in
      this paper provides a versatile interface between the conventional free-space
      optics and a two-dimensional platform such as surface plasmonics. 

PMID- 25995073
TI  - Reliability of phenotypic early-onset ataxia assessment: a pilot study.
AB  - AIM: To investigate the interobserver agreement on phenotypic early-onset ataxia
      (EOA) assessment and to explore whether the Scale for Assessment and Rating of
      Ataxia (SARA) could provide a supportive marker. METHOD: Seven movement disorder
      specialists provided independent phenotypic assessments of potentially ataxic
      motor behaviour in 40 patients (mean age 15y [range 5-34]; data derived from
      University Medical Center Groningen medical records 1998-2012). We determined
      interobserver agreement by Fleiss' kappa. Furthermore, we compared percentage
      SARA subscores ([subscore/total score]*100%) between 'indisputable' (primary
      ataxia recognition by at least six observers) and 'mixed' (ataxia recognition,
      unfulfilling 'indisputable' criteria) EOA phenotypes. RESULTS: Agreement on
      phenotypic EOA assessment was statistically significant (p<0.001), but of
      moderate strength (Fleiss' kappa=0.45; 95% CI 0.38-0.51). During mild disease
      progression, percentage SARA gait subscores discriminated between 'indisputable'
      and 'mixed' EOA phenotypes. In patients with percentage SARA gait subscores >30%,
      primary ataxia was more frequently present than in those with subscores <30%
      (p=0.001). INTERPRETATION: Among movement-disorder professionals from different
      disciplines, interobserver agreement on phenotypic EOA recognition is of limited
      strength. SARA gait subscores can provide a supportive discriminative marker
      between EOA phenotypes. Hopefully, future phenotypic insight will contribute to
      the inclusion of uniform, high-quality data in international EOA databases.

PMID- 25995074
TI  - Contribution of the external urethral sphincter to urinary void size in
      unanesthetized unrestrained rats.
AB  - AIMS: In anesthetized rats, voiding is typically associated with phasic
      activation (bursting) of the external urethral sphincter (EUS). During
      spontaneous voiding in unanesthetized, unrestrained rats, EUS bursting is the
      most common form of EUS activity exhibited, but it is not necessary for
      productive voiding to occur. The aim of the present study was to determine which
      aspects of EUS activity contributed to void size during bursting and non-bursting
      voiding in conscious, freely moving rats. METHODS: Female rats were implanted
      with electrodes adjacent to the EUS for recording electromyographic activity
      (EMG). EUS EMG recordings were performed during 24-hr sessions in a metabolic
      cage while voided urine was continuously collected and weighed. RESULTS: Void
      size was positively correlated with the duration of the intra-burst silent and
      active periods and variables reflecting the overall intensity and duration of
      bursting, particularly at lower frequencies within the 3-10 Hz range of EUS
      bursting. In addition, void size was inversely related to the frequency of
      bursting and to the average EMG amplitude during voiding, both in voids with and
      without bursting. CONCLUSIONS: EUS bursting contributes to productive voiding
      when bursting is present. Lower bursting frequencies elicit more productive
      voiding than do higher frequencies. In the absence of bursting, the association
      of increased void size with smaller average EUS EMG amplitude suggests that
      conscious rats can perform synergic voiding (i.e., bladder contraction with EUS
      relaxation) that is comparable to that seen in humans and other typically non
      bursting species. Neurourol. Urodynam. 35:696-702, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25995076
TI  - Erratum to: Chiral ligand-exchange high-performance liquid chromatography with
      copper (II)-L-phenylalanine complexes for separation of 3,4-dimethoxy-alpha
      methylphenylalanine racemes.

PMID- 25995075
TI  - The Role of Information Provision in Economic Evaluations of Newborn Bloodspot
      Screening: A Systematic Review.
AB  - BACKGROUND: The extent to which economic evaluations have included the healthcare
      resource and outcome-related implications of information provision in national
      newborn bloodspot screening programmes (NBSPs) is not currently known.
      OBJECTIVES: To identify if, and how, information provision has been incorporated
      into published economic evaluations of NBSPs. METHODS: A systematic review of
      economic evaluations of NBSPs (up to November 2014) was conducted. Three
      electronic databases were searched (Ovid: Medline, Embase, CINAHL) using an
      electronic search strategy combining a published economic search filter with
      terms related to national NBSPs and screening-related technologies. These
      electronic searches were supplemented by searching the NHS Economic Evaluations
      Database (NHS EED) and hand-searching identified study reference lists. The
      results were tabulated and summarised as part of a narrative synthesis. RESULTS:
      A total of 27 economic evaluations [screening-related technologies (n = 11) and
      NBSPs (n = 16)] were identified. The majority of economic evaluations did not
      quantify the impact of information provision in terms of healthcare costs or
      outcomes. Five studies did include an estimate of the time cost associated with
      information provision. Four studies included a value to reflect the disutility
      associated with parental anxiety caused by false-positive results, which was used
      as a proxy for the impact of imperfect information. CONCLUSION: A limited
      evidence base currently quantifies the impact of information provision on the
      healthcare costs and impact on the users of NBSPs; the parents of newborns. We
      suggest that economic evaluations of expanded NBSPs need to take account of
      information provision otherwise the impact on healthcare costs and the outcomes
      for newborns and their parents may be underestimated.

PMID- 25995077
TI  - Demonstration of glucose-6-phosphate hydrogen 5 enrichment from deuterated water
      by transaldolase-mediated exchange alone.
AB  - PURPOSE: Enrichment of glucose position 5 (H5) from deuterated water ((2)H2O) is
      widely used for quantifying gluconeogenesis. Exchanges of hexose and triose
      phosphates mediated by transaldolase have been postulated to enrich H5
      independently of gluconeogenesis, but to date this mechanism has not been proven.
      We determined the enrichment of glucose-6-phosphate (G6P), the immediate
      precursor of endogenously produced glucose, from (2)H2O in erythrocyte hemolysate
      preparations. Here, transaldolase exchange is active but gluconeogenesis is
      absent. METHODS: Hemolysates were prepared from human erythrocytes and incubated
      with a buffer containing 5% [U-(13)C]G6P, unlabeled fructose 1,6-bisphosphate,
      and 10% (2)H2O. G6P (2)H-enrichment and (13)C-isotopomer distributions were
      analyzed by (2)H and (13)C NMR following derivatization to monoacetone glucose.
      RESULTS: (2)H NMR analysis revealed high (2)H-enrichment of G6P hydrogens 2, 4,
      and 5; low enrichment of hydrogen 3, and residual enrichments of hydrogens 1, 6R,
      and 6S. (13)C NMR isotopomer analysis revealed that [U-(13)C]G6P was converted to
      [1,2,3-(13)C3]G6P, a predicted product of transaldolase-mediated exchange, as
      well as [1,2-(13)C2]G6P and [3-(13)C]G6P, predicted products of combined
      transaldolase and transketolase exchanges. CONCLUSION: Hydrogen 5 of G6P was
      enriched from (2)H2O through exchanges mediated by transaldolase. These studies
      prove that G6P can be enriched in hydrogen 5 by (2)H2O independently of
      gluconeogenesis.

PMID- 25995079
TI  - Hyperthermia approaches for enhanced delivery of nanomedicines to solid tumors.
AB  - Drug delivery to solid tumors has received much attention in order to reduce
      harmful side effects and improve the efficacy of treatment. Different strategies
      have been utilized with nanoparticle drug delivery systems, or nanomedicines,
      including passive and active targeting strategies, as well as the incorporation
      of stimuli sensitivity. Additionally, hyperthermia has been used in combination
      with such systems to further improve accumulation, localization, penetration, and
      subsequently efficacy. Localized hyperthermia within the solid tumor tissue can
      be applied through different mechanisms able to trigger vascular and cellular
      mechanisms for enhanced delivery of nanomedicines. This review covers the use of
      nanoparticles in drug delivery, the different methods for inducing localized
      hyperthermia, combination effects of hyperthermia, and successful strategies for
      improving the delivery of nanomedicines using hyperthermia.

PMID- 25995078
TI  - Fibroblast activation protein increases metastatic potential of fibrosarcoma line
      HT1080 through upregulation of integrin-mediated signaling pathways.
AB  - The serine protease fibroblast activation protein (FAP) is selectively expressed
      on tumour-associated fibroblasts in most human epithelial tumours, as well as on
      some mesenchymal tumours such as sarcoma. High FAP expression is most often
      associated with poor outcome and increased metastasis. Here, we compare the in
      vitro metastatic potential of HT1080 fibrosarcoma cells with and without FAP
      expression in order to elucidate the mechanism by which FAP may influence
      metastasis. In the presence of FAP, cells were more adhesive to extracellular
      matrix proteins and migrated and invaded through Matrigel to a greater degree.
      The anti-FAP antibody ESC11, which caused internalization of FAP, decreased
      adhesion and migration, but only when cells expressed FAP. It was also found that
      blocking activity of integrins beta1 and alphavbeta3 reduced both cell adhesion
      and migration and this effect was much more marked in FAP-expressing HT1080 cells
      than mock-transfected HT1080 cells. The expression or activation of intracellular
      proteins that form part of the downstream signaling of integrins, including
      integrin-linked kinase, Rac1 and focal adhesion kinase, was also upregulated when
      FAP was expressed, suggesting that FAP not only upregulates metastatic-like cell
      behaviours through interaction with integrins, but also influences the
      intracellular signaling of integrins. This was confirmed using both PI3 kinase
      and Src kinase inhibitors, which decreased adhesion and migration in FAP
      expressing cells, but did not affect mock-transfected HT1080 cells. FAP is
      therefore a useful target for anti-cancer therapy, as not only is its expression
      tumour-selective, but its downregulation has the potential to reduce incidence of
      metastasis.

PMID- 25995080
TI  - AAC Interventions for Individuals with Autism Spectrum Disorders: State of the
      Science and Future Research Directions.
AB  - Augmentative and alternative communication (AAC) provides a means of effective
      communication to individuals with autism spectrum disorder (ASD), many of whom
      are unable to use conventional speech effectively. The purposes of this article
      are (a) to summarize and synthesize the last few decades of research on the use
      of AAC with people with ASD; (b) to indicate implications of this research for
      stakeholders such as people with ASD, their family members, and educators with
      whom they work; and (c) to outline priorities for future research to improve
      communication and other outcomes for individuals with ASD and their loved ones.
      People with ASD stand to greatly benefit from AAC, particularly with current AAC
      technologies, as described in this article. 

PMID- 25995081
TI  - Local government capacity to deliver health promotion initiatives: a case study.

PMID- 25995082
TI  - Effectiveness of fecal immunochemical testing in reducing colorectal cancer
      mortality from the One Million Taiwanese Screening Program.
AB  - BACKGROUND: The effectiveness of fecal immunochemical testing (FIT) in reducing
      colorectal cancer (CRC) mortality has not yet been fully assessed in a large,
      population-based service screening program. METHODS: A prospective cohort study
      of the follow-up of approximately 5 million Taiwanese from 2004 to 2009 was
      conducted to compare CRC mortality for an exposed (screened) group and an
      unexposed (unscreened) group in a population-based CRC screening service
      targeting community residents of Taiwan who were 50 to 69 years old. Given
      clinical capacity, this nationwide screening program was first rolled out in
      2004. In all, 1,160,895 eligible subjects who were 50 to 69 years old (ie, 21.4%
      of the 5,417,699 subjects of the underlying population) participated in the
      biennial nationwide screening program by 2009. RESULTS: The actual effectiveness
      in reducing CRC mortality attributed to the FIT screening was 62% (relative rate
      for the screened group vs the unscreened group, 0.38; 95% confidence interval,
      0.35-0.42) with a maximum follow-up of 6 years. The 21.4% coverage of the
      population receiving FIT led to a significant 10% reduction in CRC mortality
      (relative rate, 0.90; 95% confidence interval, 0.84-0.95) after adjustments for a
      self-selection bias. CONCLUSIONS: This large, prospective Taiwanese cohort
      undergoing population-based FIT screening for CRC had the statistical power to
      demonstrate a significant CRC mortality reduction, although the follow-up time
      was short. Although such findings are informative for health decision makers,
      continued follow-up of this large cohort will be required to estimate the long
      term impact of FIT screening if the covered population is expanded.

PMID- 25995084
TI  - Elucidating the mechanism of interaction between peptides and inorganic surfaces.
AB  - Understanding the mechanism of interaction between peptides and inorganic
      materials is of high importance for the development of new composite materials.
      Here, we combined an experimental approach along with molecular simulations in
      order to gain insights into this binding process. Using single molecule force
      spectroscopy by atomic force microscopy and molecular simulations we studied the
      binding of a peptide towards an inorganic substrate. By performing alanine scan
      we examined the propensity of each amino acid in the peptide sequence to bind the
      substrate (mica). Our results indicate that this binding is not controlled by the
      specific sequence of the peptide, but rather by its conformational freedom in
      solution versus its freedom when it is in proximity to the substrate. When the
      conformational freedom of the peptide is identical in both environments, the
      peptide will not adhere to the substrate. However, when the conformational
      freedom is reduced, i.e., when the peptide is in close proximity to the
      substrate, binding will occur. These results shed light on the interaction
      between peptides and inorganic materials. 

PMID- 25995083
TI  - Evolutionary-guided de novo structure prediction of self-associated transmembrane
      helical proteins with near-atomic accuracy.
AB  - How specific protein associations regulate the function of membrane receptors
      remains poorly understood. Conformational flexibility currently hinders the
      structure determination of several classes of membrane receptors and associated
      oligomers. Here we develop EFDOCK-TM, a general method to predict self-associated
      transmembrane protein helical (TMH) structures from sequence guided by co
      evolutionary information. We show that accurate intermolecular contacts can be
      identified using a combination of protein sequence covariation and TMH binding
      surfaces predicted from sequence. When applied to diverse TMH oligomers,
      including receptors characterized in multiple conformational and functional
      states, the method reaches unprecedented near-atomic accuracy for most targets.
      Blind predictions of structurally uncharacterized receptor tyrosine kinase TMH
      oligomers provide a plausible hypothesis on the molecular mechanisms of disease
      associated point mutations and binding surfaces for the rational design of
      selective inhibitors. The method sets the stage for uncovering novel determinants
      of molecular recognition and signalling in single-spanning eukaryotic membrane
      receptors. 

PMID- 25995085
TI  - Facile preparation of high-performance elastically stretchable interconnects.
AB  - Sites on poly(dimethylsiloxane) are selected by ultraviolet exposure. In a
      subsequent electroless deposition, solid silver films are created on the selected
      sites only. In this way, facile vacuum-free deposition of electrodes from the
      liquid phase and their photoresist- and solvent-free patterning are realized. The
      technique enables reliable rigid-to-soft interconnects that are reversibly
      stretchable under arbitrary and changing stretching directions. 

PMID- 25995086
TI  - [Complications in the therapy of spontaneous pneumothorax].
AB  - The therapy of spontaneous pneumothorax is a common necessity in hospitals of all
      care hierarchies In addition to sufficient primary treatment by placement of a
      thorax drainage, knowledge of complicationg constellations, recognition of
      complications and irregular courses during the therapy of spontaneous
      pneumothorax are of fundamental importance for achieving a satisfactory treatment
      outcome. Furthermore, the enlightenment of patients regarding the pathogenesis of
      the disease, possible measures for influencing the recurrence rate and
      information about future behavioral and lifestyle modifications are important.
      The principal complications during hospital treatment can be subdivided into
      complications of the surgical placement of the thorax drain and relief of the
      pleural cavity, problems in the management of treatment of the pleural negative
      pressure, the possibly demanding management of a persisting air leak and the
      individualized decision-making with respect to an interventional or operative
      procedure. The most common complicating constellations and possible complications
      during the inpatient hospital stay are described, the. 

PMID- 25995088
TI  - [Julius Springer prize for surgery 2015 awarded].

PMID- 25995087
TI  - [Intraoperative bleeding during thoracic surgery : avoidance strategies and
      surgical treatment concepts].
AB  - ABSRACT:  BACKGROUND: As a direct result of the thoracic anatomy, heavy bleeding
      is possible during nearly all central resections in thoracic surgery. OBJECTIVE:
      Description of the incidence of intraoperative bleeding including avoidance
      strategies and treatment concepts. Presentation of special anatomical features of
      pulmonary arteries. MATERIAL AND METHODS: A literature search was performed in
      Pubmed, medline and by manual searching. Publications from the last 60 years were
      analyzed and the results are summarized in a structured review. RESULTS: Little
      data is available on the incidence of intraoperative bleeding during thoracic
      surgery. Most data were collected retrospectively. For mediastinoscopy the
      incidence of severe bleeding is 0.2 %, for minimally invasive anatomical
      resections the incidence of intraoperative bleeding is 4.7 % and for open surgery
      5 %. Bleeding from the central pulmonary artery can take a dramatic course and
      requires rapid and targeted therapy. DISCUSSION: Knowledge of the anatomical
      topographic details, the structure, the course and the specific features of the
      vessels of the lungs is essential to prevent and treat bleeding. Avoidance
      strategies include techniques of proximal and distal vessel control,
      intrapericardial preparation and sharp preparation in general. Techniques of
      forward-looking preparation and well-prepared exit strategies in case of bleeding
      have to be part of the training in thoracic surgery.

PMID- 25995089
TI  - [Complex vacuum therapy of an abdominal abscess from gastric perforation : case
      report of innovative operative endoscopic management].
AB  - BACKGROUND: The simultaneous use of abdominal and endoscopic vacuum therapy in a
      case of an abdominal abscess caused by gastric perforation is demonstrated and
      innovative operative endoscopic management is described. CASE REPORT: A computed
      tomography scan performed on a 67-year-old female patient showed a large abscess
      of the upper abdominal cavity where laparoscopic fundoplication had been
      performed 6 months previously. Endoscopy showed a transmural perforation of the
      dorsal wall of the stomach. The gastric perforation was closed and drained using
      intracavitary endoscopic vacuum therapy. Open pore polyurethane foam drainage was
      inserted through the defect into the extraluminal cavity for 3 days. A second
      period of therapy followed using intraluminal therapy with total drainage of the
      stomach, simultaneous enteral nutrition via a jejunal tube and a vacuum pressure
      of - 125 mmHg was applied with an electronic vacuum device. The abdominal abscess
      was drained via laparotomy and intra-abdominal vacuum therapy was performed with
      an open pore double-layered film using a vacuum pressure of - 75 mmHg. The
      perforation defect was not treated by operative means. Abdominal vacuum therapy
      ended 3 days postoperatively and the abdominal wall was closed by suture.
      Endoscopic vacuum therapy of the gastric perforation was terminated after 7 days
      and primary wound healing could then be achieved. CONCLUSION: Use of endoscopic
      and abdominal vacuum therapy as well as new open pore material is an innovative
      option for operative management.

PMID- 25995090
TI  - [Comment to: complex vacuum therapy of an abdominal abscess from gastric
      perforation. Case report of innovative operative endoscopic management].

PMID- 25995091
TI  - [Anti-TNF antibodies in prevention and treatment of postoperative recurrence of
      Crohn's disease].

PMID- 25995092
TI  - [Recanalisation therapy of deep leg and pelvic vein thrombosis].
AB  - The conservative treatment of deep leg and pelvic vein thrombosis leads to
      permanent damage of recanalised veins, which in cases of long distance clots as
      well as involvement of the pelvic level, increase the risk of developing a
      postthrombotic syndrome. Such subsequent damage of the deep veins can only be
      avoided if occluded veins are rapidly recanalised and the function of the valves
      is successfully reestablished. Recanalisation may consist of surgical, fibrolytic
      and interventional methods and aims to minimize any subsequent damage; however no
      potential benefit of recanalisation versus standard treatment has yet been proven
      by means of methodologically adequate comparative studies. Thus, the indications
      for recanalisation must remain strict and be founded on a thorough risk-benefit
      assessment. 

PMID- 25995093
TI  - Concomitant chemoradiotherapy for advanced squamous cell carcinoma of the
      temporal bone.
AB  - BACKGROUND: The purpose of this study was to analyze outcomes for the treatment
      of locally advanced temporal bone cancer by means of concomitant
      chemoradiotherapy (CCRT) with a combination of cisplatin (CDDP), 5-fluorouracil
      (5-FU), and docetaxel (TPF). METHODS: Between 2006 and 2011, 34 patients with
      squamous cell carcinoma of the temporal bone were treated at Kobe University
      Hospital. Medical records were retrospectively reviewed to obtain information
      concerning patient characteristics, extent of disease, treatment, adverse events,
      and oncologic results. RESULTS: Ten patients were treated with CCRT using TPF
      regimen. The 5-year overall survival rate and disease-free survival rate were
      both 60%. Of special interest is that even for patients with unresectable T4
      disease, the 5-year overall survival rate was 56%. CONCLUSION: The results of our
      study indicate that CCRT with TPF for locally advanced temporal bone cancer is an
      effective and promising regimen. (c) 2015 Wiley Periodicals, Inc. Head Neck 38:
      E949-E953, 2016.

PMID- 25995094
TI  - Water-soluble carboranyl-phthalocyanines for BNCT. Synthesis, characterization,
      and in vitro tests of the Zn(II)-nido-carboranyl-hexylthiophthalocyanine.
AB  - The zinc(II) complex of the octa-anionic 2,3,9,10,16,17,23,24-octakis-(7-methyl
      7,8-dicarba-nido-undeca-boran-8-yl)hexyl-thio-6,13,20,27-phthalocyanine (nido
      [ZnMCHESPc]Cs8, 7) has been obtained in the form of caesium salt through mild
      deboronation of the neutral precursor, the closo-[ZnMCHESPc] complex, 6, with
      CsF. 6 has been synthesized, in turn, by heating a finely ground mixture of the
      appropriate phthalonitrile and zinc(II) acetate at 180.0  degrees C. The
      complexes have been characterized by elemental analyses, FT-IR, UV-visible
      absorption and fluorescence emission spectroscopy, and their structures were
      assessed by (1)H, (13)C, (11)B, and two-dimensional homo- and hetero-correlated
      NMR spectroscopy experiments. 7 showed appreciable solubility in water solution,
      together with a marked tendency to aggregate. Aggregation of 7 in the hydrotropic
      medium resulted in significant fluorescence quenching. Instead, fluorescence
      quantum yields (Phi(F)) of 0.14 and 0.08, and singlet oxygen quantum yields
      (Phi(Delta)) of 0.63 and 0.24 were obtained for 6 and 7, respectively, in a DMF
      solution. In vitro boron neutron capture therapy (BNCT) experiments, employing
      boron imaging techniques as implemented in qualitative and quantitative neutron
      autoradiography methods, showed that 7 is capable of increasing the boron
      concentration of two selected cancerous cell lines, the DHD/K12/TRb of rat colon
      adenocarcinoma and UMR-106 of rat osteosarcoma, with the large-size Cs(+) counter
      ions used to neutralize the negatively charged carborane polyhedra not presenting
      a significant obstacle to the process. Taken together, BNCT and photophysical
      measurement results indicated that 7 is potentially suitable for bimodal or
      multimodal anticancer therapy.

PMID- 25995095
TI  - Tunable emission in lanthanide coordination polymer gels based on a rationally
      designed blue emissive gelator.
AB  - Rational design and synthesis of a new low molecular weight gelator (LMWG) having
      9,10-diphenylanthracene core and terminal terpyridine is reported. Tb(III) and
      Eu(III) ion coordination to a LMWG results in green and pink emissive
      coordination polymer gels, respectively, with coiled nanofiber morphology.
      Further, control over stoichiometry of LMWG:Tb(III):Eu(III) leads to yellow and
      white light emitting bimetallic gels. 

PMID- 25995096
TI  - Hyperelastic modeling of swelling in fibrous soft tissue with application to
      tracheal angioedema.
AB  - Angioedema, the rapid swelling of under-skin tissue, is typically triggered by
      complex biochemical processes that disrupt an original steady state filtration of
      liquid through the tissue. Swelling stabilizes once a new steady state is
      achieved in which the tissue has significantly increased liquid content. These
      processes are controlled by events at the molecular to the cellular length scale.
      For describing consequences at organ level length scales it is useful to invoke
      consolidated continuum mechanics treatments within a generalized hyperelastic
      framework. We describe the challenges associated with such modeling and
      demonstrate their use in the context of tracheal angioedema. The trachea is
      modeled as a two layered cylindrical tube. The inner layer and outer layer
      represent the soft mucosal tissue and the stiffer cartilaginous tissue
      respectively. Axially oriented fibers contribute anisotropy to the inner layer,
      and the swelling is largely confined to this layer. A boundary value problem is
      formulated; existence and uniqueness is verified. Numerical solutions track
      airway constriction as a function of mucosal swelling. 

PMID- 25995097
TI  - In vitro exposure: Linear and non-linear thermodynamic events in Petri dishes.
AB  - We conducted an electromagnetic-thermal analysis of Petri dishes filled with
      different medium volumes under different radio frequency exposure conditions with
      the aim of identifying linear and non-linear parameters that might explain
      contradictory results of many in vitro bioelectromagnetic experiments. We found
      that power loss density and temperature depend on shape, size, and orientation of
      the exposed sample with respect to direction of incident energy, showing that the
      liquid medium acts as a receiving antenna. In addition, we investigated the
      possibility of convection from thermodynamic principles within the liquid medium.
      For a 35 mm diameter Petri dish, a 2 or 4 ml medium volume is too small to
      support vertical convection. Conversely, horizontal convective motion is possible
      for H-polarization exposures at 1.8 GHz.

PMID- 25995099
TI  - Two nights of sleep deprivation with or without energy restriction does not
      impair the thermal response to cold.
AB  - PURPOSE: In persons completing exhaustive daily exercise, sleep and energy
      restriction have been highlighted as risk factors for hypothermia in cold
      environments. The present study therefore sought to determine the effect of sleep
      deprivation (SDEP), with and without energy restriction, on the thermal response
      to cold. METHODS: In a random order, ten recreationally active men (mean +/- SD:
      age 25 +/- 6 years, body fat 17 +/- 5 %) completed three 53 h trials: a control
      (CON: 436 min/night sleep), SDEP (0 min sleep), and sleep deprivation and energy
      restriction (SDEP + ER: 0 min sleep and 10% daily energy requirements).
      Exhaustive exercise was completed after 5 and 29 h. After 53 h participants
      completed a semi-nude seated cold air test (CAT, 0  degrees C), for 4 h or until
      rectal core temperature (T re) reached 36  degrees C. RESULTS: Two nights of
      sleep and energy restriction did not impair the thermal response to cold (T re,
      CON 36.15 +/- 0.20  degrees C, SDEP 36.30 +/- 0.15  degrees C, SDEP + ER 36.25 +/
      0.20  degrees C, P = 0.25). Rewarming was also similar as indicated by 1 h post
      CAT T re (P = 0.78). In contrast, perceived thermal discomfort during the initial
      hour of the CAT tended to be greater after SDEP and SDEP + ER (P <= 0.1).
      CONCLUSION: Sleep and energy restriction, at least as evaluated within this
      experiment, should be considered minimal risk factors for hypothermia. The
      greater perception of cold discomfort at the same body temperature suggests that
      sleep and energy restriction may actually reduce cold injury risk, as people are
      likely to engage earlier in normal behavioral cold adaptation.

PMID- 25995098
TI  - Neuromodulation therapies for geriatric depression.
AB  - Depression is frequent in old age and its prognosis is poorer than in younger
      populations. The use of pharmacological treatments in geriatric depression is
      limited by specific pharmacodynamic age-related factors that can diminish
      tolerability and increase the risk of drug interactions. The possibility of
      modulating cerebral activity using brain stimulation techniques could result in
      treating geriatric depression more effectively while reducing systemic side
      effects and medication interactions. This may subsequently improve treatment
      adherence and overall prognosis in the older patient. Among clinically available
      neuromodulatory techniques, electroconvulsive therapy (ECT) remains the gold
      standard for the treatment of severe depression in the elderly. Studies have
      proven that ECT is more effective and has a faster onset of action than
      antidepressants in the treatment of severe, unipolar, geriatric depression and
      that older age is a predictor of rapid ECT response and remission. The
      application of novel and more tolerable forms of ECT for geriatric depression is
      currently being examined. Preliminary results suggest that right unilateral
      ultrabrief ECT (RUL-UB ECT) is a promising intervention, with similar efficacy to
      brief-pulse ECT and fewer adverse cognitive effects. Overall findings in
      repetitive transcranial magnetic stimulation (rTMS) suggest that it is a safe
      intervention in geriatric depression. Higher rTMS stimulation intensity and more
      treatments may need to be given in the elderly to achieve optimal results. There
      is no specific data on vagus nerve stimulation in the elderly. Transcranial
      direct current stimulation, magnetic seizure therapy and deep brain stimulation
      are currently experimental, and more data from geriatric samples is needed.

PMID- 25995100
TI  - Temporal dynamics of the circadian heart rate following low and high volume
      exercise training in sedentary male subjects.
AB  - PURPOSE: Increased risk of arrhythmic events occurs at certain times during the
      circadian cycle with the highest risk being in the second and fourth quarter of
      the day. Exercise improves treatment outcome in individuals with cardiovascular
      disease. How different exercise protocols affect the circadian rhythm and the
      associated decrease in adverse cardiovascular risk over the circadian cycle has
      not been shown. METHODS: Fifty sedentary male participants were randomized into
      an 8-week high volume and moderate volume training and a control group. Heart
      rate was recorded using Polar Electronics and investigated with Cosinor analysis
      and by Poincare plot derived features of SD1, SD2 and the complex correlation
      measure (CCM) at 1-h intervals over the 24-h period. RESULTS: Moderate exercise
      significantly increased vagal modulation and the temporal dynamics of the heart
      rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007
      respectively). High volume exercise had a similar effect on vagal output (p =
      0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the
      circadian heart rate displays a shift in the acrophage following moderate and
      high volume exercise from before waking (1st quarter) to after waking (2nd
      quarter of day). CONCLUSIONS: Our results suggest that exercise shifts vagal
      influence and increases temporal dynamics of the heart rate to the 2nd quarter of
      the day and suggest that this may be the underlying physiological change leading
      to a decrease in adverse arrhythmic events during this otherwise high-risk
      period.

PMID- 25995101
TI  - Reply to J. Magalon et al.

PMID- 25995102
TI  - Optimized time-resolved imaging of contrast kinetics (TRICKS) in dynamic contrast
      enhanced MRI after peptide receptor radionuclide therapy in small animal tumor
      models.
AB  - Anti-tumor efficacy of targeted peptide-receptor radionuclide therapy (PRRT)
      relies on several factors, including functional tumor vasculature. Little is
      known about the effect of PRRT on tumor vasculature. With dynamic contrast
      enhanced (DCE-) MRI, functional vasculature is imaged and quantified using
      contrast agents. In small animals DCE-MRI is a challenging application. We
      optimized a clinical sequence for fast hemodynamic acquisitions, time-resolved
      imaging of contrast kinetics (TRICKS), to obtain DCE-MRI images at both high
      spatial and high temporal resolution in mice and rats. Using TRICKS, functional
      vasculature was measured prior to PRRT and longitudinally to investigate the
      effect of treatment on tumor vascular characteristics. Nude mice bearing H69
      tumor xenografts and rats bearing syngeneic CA20948 tumors were used to study
      perfusion following PRRT administration with (177) lutetium octreotate. Both semi
      quantitative and quantitative parameters were calculated. Treatment efficacy was
      measured by tumor-size reduction. Optimized TRICKS enabled MRI at 0.032 mm(3)
      voxel size with a temporal resolution of less than 5 s and large volume coverage,
      a substantial improvement over routine pre-clinical DCE-MRI studies. Tumor
      response to therapy was reflected in changes in tumor perfusion/permeability
      parameters. The H69 tumor model showed pronounced changes in DCE-derived
      parameters following PRRT. The rat CA20948 tumor model showed more heterogeneity
      in both treatment outcome and perfusion parameters. TRICKS enabled the
      acquisition of DCE-MRI at both high temporal resolution (Tres ) and spatial
      resolutions relevant for small animal tumor models. With the high Tres enabled by
      TRICKS, accurate pharmacokinetic data modeling was feasible. DCE-MRI parameters
      revealed changes over time and showed a clear relationship between tumor size and
      Ktrans .

PMID- 25995104
TI  - Inhospital mortality among clinical and surgical inpatients recently diagnosed
      with venous thromboembolic disease.
AB  - Venous thromboembolism (VTE) is the most common cause of preventable mortality in
      hospitalized patients, and pulmonary embolism is responsible for 5-10 % of all
      hospital deaths. To estimate the hospital mortality in hospitalized patients who
      developed VTE during hospitalization. Prospective cohort of all adult inpatients
      >17 years admitted to the hospital between August 2006 and August 2013, and
      follow-up until discharge to measure death. VTE incident cases were captured
      prospectively from the Institutional Registry of Thromboembolic disease in a
      tertiary hospital care in Buenos Aires. In hospital global mortality and fatality
      rate of inpatients with VTE was calculated. The cumulative incidence of VTE was
      1.8 % (95 % CI 1.77-1.93 %), representing 1.32 % (95 % CI 1.23-1.41 %) in the
      subgroup of surgical patients and 2.1 % (95 % CI 1.9-2.2 %) in clinical
      inpatients. The overall hospital mortality was 2.4 % (95 % CI 2.35-2.53); being
      3.95 % (95 % CI 3.78-4.12) in clinical inpatients and 1.15 % (95 % CI 1.06-1.23)
      in surgical patients. The death in patients who had developed VTE, represented
      between 4 and 7 % of hospital deaths, and it increases with age in both clinical
      and surgical patients. In Argentina there are few data of hospital mortality in
      patients with VTE. This information is useful when assessing the need for
      resources for prevention, diagnosis and treatment in inpatients.

PMID- 25995103
TI  - Tissue plasminogen activator for acute ischemic stroke: calculation of dose based
      on estimated patient weight can increase the risk of cerebral bleeding.
AB  - A dose of 0.9 mg/kg of intravenous tissue plasminogen activator (t-PA) has proven
      to be beneficial in the treatment of acute ischemic stroke (AIS). Dosing of t-PA
      based on estimated patient weight (PW) increases the likelihood of errors. Our
      objectives were to evaluate the accuracy of estimated PW and assess the
      effectiveness and safety of the actual applied dose (AAD) of t-PA. We performed a
      prospective single-center study of AIS patients treated with t-PA from May 2010
      to December 2011. Dose was calculated according to estimated PW. Patients were
      weighed during the 24 h following treatment with t-PA. Estimation errors and AAD
      were calculated. Actual PW was measured in 97 of the 108 included patients. PW
      estimation errors were recorded in 22.7 % and were more frequent when weight was
      estimated by stroke unit staff (44 %). Only 11 % of patients misreported their
      own weight. Mean AAD was significantly higher in patients who had intracerebral
      hemorrhage (ICH) after t-PA than in patients who did not (0.96 vs. 0.92 mg/kg; p
      = 0.02). Multivariate analysis showed an increased risk of ICH for each 10 %
      increase in t-PA dose above the optimal dose of 0.90 mg/kg (OR 3.10; 95 % CI 1.14
      8.39; p = 0.026). No effects of t-PA misdosing were observed on symptomatic ICH,
      functional outcome or mortality. Estimated PW is frequently inaccurate and leads
      to t-PA dosing errors. Increasing doses of t-PA above 0.90 mg/kg may increase the
      risk of ICH. Standardized weighing methods before t-PA is administered should be
      considered.

PMID- 25995105
TI  - Margaret McCartney: Second use patents--why do we have to prescribe branded
      Lyrica for pain?

PMID- 25995106
TI  - Editorial expression of concern.

PMID- 25995107
TI  - A forgotten chapter in the history of the renal circulation: the Josep Trueta and
      Homer Smith intellectual conflict.
AB  - This article reviews the pioneering and visionary contributions of the Catalan
      surgeon Josep Trueta (1897-1977) to the changes in renal circulation that
      contribute to the pathogenesis of acute renal failure (ARF). An erudite scientist
      with eclectic interests in physiology, orthopedics, politics, and medical
      history, Trueta's initial involvement in wound healing as a trauma surgeon during
      the Spanish Civil War and the London Blitz is what prompted him to postulate that
      a trauma-induced "neural effect" on the renal vasculature, with resultant renal
      arterial constriction could cause ARF. To test his hypothesis, Trueta assembled
      an experienced radiologist, a renowned physiologist, and a renal pathologist to
      study ARF in Oxford. They investigated the renal circulation of rabbits in
      response to diverse traumatic conditions by injecting a radio-opaque substance,
      using cine-radiography to visualize the flow of blood through the renal
      vasculature. Trueta's suggestion of renal cortical ischemia and diversion of
      blood to the less resistant medullary circulation (Trueta shunt) was criticized
      by Homer Smith and coworkers. In contrast to Homer Smith's data, which were
      derived from clearance studies and renal arteriovenous oxygen, Trueta used the
      diametrical opposite method of "direct" observation of the renal circulation.
      Their differing methodologies, direct visualization of the renal circulation as
      opposed to inferred computations from clearance studies, accounts for some of
      their conflicting theories. Nevertheless, the proposal of disparate renal flow
      compartments focused attention on intrarenal hemodynamics. Trueta's focus on
      renal cortical ischemia was ultimately validated by the studies of Barger in the
      dog and Hollenberg and Epstein in human subjects.

PMID- 25995108
TI  - Nephron-specific deletion of the prorenin receptor causes a urine concentration
      defect.
AB  - The prorenin receptor (PRR), a recently discovered component of the renin
      angiotensin system, is expressed in the nephron in general and the collecting
      duct in particular. However, the physiological significance of nephron PRR
      remains unclear, partly due to developmental abnormalities associated with global
      or renal-specific PRR gene knockout (KO). Therefore, we developed mice with
      inducible nephron-wide PRR deletion using Pax8-reverse tetracycline
      transactivator and LC-1 transgenes and loxP flanked PRR alleles such that
      ablation of PRR occurs in adulthood, after induction with doxycycline. Nephron
      specific PRR KO mice have normal survival to ~1 yr of age and no renal
      histological defects. Compared with control mice, PRR KO mice had 65% lower
      medullary PRR mRNA and protein levels and markedly diminished renal PRR
      immunofluorescence. During both normal water intake and mild water restriction,
      PRR KO mice had significantly lower urine osmolality, higher water intake, and
      higher urine volume compared with control mice. No differences were seen in urine
      vasopressin excretion, urine Na(+) and K(+) excretion, plasma Na(+), or plasma
      osmolality between the two groups. However, PRR KO mice had reduced medullary
      aquaporin-2 levels and arginine vasopressin-stimulated cAMP accumulation in the
      isolated renal medulla compared with control mice. Taken together, these results
      suggest nephron PRR can potentially modulate renal water excretion. 

PMID- 25995109
TI  - Role of Na+/H+ exchanger regulatory factor 1 in forward trafficking of the type
      IIa Na+-Pi cotransporter.
AB  - Na+/H+ exchanger regulatory factor (NHERF1) plays a critical role in the renal
      transport of phosphate by binding to Na+-Pi cotransporter (NpT2a) in the proximal
      tubule. While the association between NpT2a and NHERF1 in the apical membrane is
      known, the role of NHERF1 to regulate the trafficking of NpT2a has not been
      studied. To address this question, we performed cell fractionation by sucrose
      gradient centrifugation in opossum kidney (OK) cells placed in low-Pi medium to
      stimulate forward trafficking of NpT2a. Immunoblot analysis demonstrated
      expression of NpT2a and NHERF1 in the endoplasmic reticulum (ER)/Golgi.
      Coimmunoprecipitation demonstrated a NpT2a-NHERF1 interaction in the ER/Golgi.
      Low-Pi medium for 4 and 8 h triggered a decrease in NHERF1 in the plasma membrane
      with a corresponding increase in the ER/Golgi. Time-lapse total internal
      reflection fluorescence imaging of OK cells placed in low-Pi medium, paired with
      particle tracking and mean square displacement analysis, indicated active
      directed movement of NHERF1 at early and late time points, whereas NpT2a showed
      active movement only at later times. Silence of NHERF1 in OK cells expressing
      green fluorescent protein (GFP)-NpT2a resulted in an intracellular accumulation
      of GFP-NpT2a. Transfection with GFP-labeled COOH-terminal (TRL) PDZ-binding motif
      deleted or wild-type NpT2a in OK cells followed by cell fractionation and
      immunoprecipitation confirmed that the interaction between NpT2a and NHERF1 was
      dependent on the TRL motif of NpT2a. We conclude that appropriate trafficking of
      NpT2a to the plasma membrane is dependent on the initial association between
      NpT2a and NHERF1 through the COOH-terminal TRL motif of NpT2a in the ER/Golgi and
      requires redistribution of NHERF1 to the ER/Golgi.

PMID- 25995110
TI  - Furosemide-induced urinary acidification is caused by pronounced H+ secretion in
      the thick ascending limb.
AB  - The loop diuretic furosemide inhibits NaCl reabsorption in the thick ascending
      limb (TAL). In addition, furosemide acidifies the urine, which is traditionally
      explained by increased Na+ loading to the distal tubule causing an activation of
      H+ secretion via H+-ATPase in alpha-intercalated cells. The inability to acidify
      urine in response to furosemide serves to diagnose distal renal tubular acidosis
      (dysfunction of alpha-intercalated cells). Since the TAL is important for
      acid/base regulation, we speculated that it is involved in furosemide-induced
      urinary acidification. Luminal furosemide (100 MUM) caused major, stable, and
      reversible intracellular alkalization (7.27 +/- 0.06 to 7.6 +/- 0.04) in isolated
      perfused murine medullary TAL and pronounced H+ secretion. This H+ secretion was
      fully inhibited with luminal amiloride (1 mM) and the Na+/H+ exchanger (NHE)3
      specific antagonist #4167 (1 MUM). Moreover, furosemide triggered a substantial
      drop of intracellular Na+ concentration in the medullary TAL. These results
      suggest that the furosemide-induced H+ secretion is a consequence of a drop in
      intracellular Na+ concentration, increasing the driving force for NHE3.
      Intriguingly, in whole animal experiments, furosemide-induced urinary
      acidification and net acid excretion were markedly reduced by specific NHE3
      inhibition. Furthermore, the furosemide-induced urinary acidification was
      partially preserved during epithelial Na+ channel inhibition with benzamil. These
      results provide new insights in the mechanism of furosemide-induced urinary
      acidification and emphasize the role of the TAL in renal acid/base handling.

PMID- 25995112
TI  - Reviewer's comment concerning "Novel posterior technique to temporize life
      threatening hemorrhage after great vessel laceration during posterior osteotomy"
      (10.1007/s00586-015-3944-8 by W. K. Cheng et al.).

PMID- 25995113
TI  - Anterior cervical intradural arachnoid cyst, a rare cause of spinal cord
      compression: a case report with video systematic literature review.
AB  - PURPOSE: Mostly seen at the thoracic level, arachnoid cysts are a very rare cause
      of cervical spinal cord compression. Generally treated by laminectomy and cyst
      fenestration, this approach does not allow removing the cyst in its entirety
      without manipulating the weakened spinal cord. The aim of this report is to
      present the case of a cervical intradural arachnoid cyst surgically removed by an
      anterior approach with corporectomy. METHODS: Here is the case of an 18-year-old
      amateur boxer presenting with a voluminous cervical intradural anterior arachnoid
      cyst, extending from C2 to C5. Symptoms were cervical pain, quadriparesis, and
      clumsiness of both arms which had appeared just after a traffic accident. An
      anterior approach was chosen, through a C5 corporectomy. RESULTS: The patient
      totally recovered from his sensitive symptoms at discharge and from his motor
      symptoms 6 weeks later. Early as well as 3-years post-operatively, MRI confirmed
      expansion of the spinal cord without any centro-medullar signal. The patient
      remained asymptomatic 3 years after surgery. Since the first report in 1974, 16
      cases of symptomatic cervical intradural arachnoid cysts were treated via a
      posterior approach, one by MRI-guided biopsy, and one was re-operated on through
      an anterior approach. For 14 patients, their conditions had improved, while one
      died of pneumonia, one presented a condition worsened, and one had a stable
      neurological status. CONCLUSION: Using an anterior approach is a safe procedure
      that allows resection of a cervical arachnoid cyst without any manipulation of
      the weakened spinal cord, while giving the best possible view.

PMID- 25995111
TI  - Downregulation of urea transporter UT-A1 activity by 14-3-3 protein.
AB  - Urea transporter (UT)-A1 in the kidney inner medulla plays a critical role in the
      urinary concentrating mechanism and thereby in the regulation of water balance.
      The 14-3-3 proteins are a family of seven isoforms. They are multifunctional
      regulatory proteins that mainly bind to phosphorylated serine/threonine residues
      in target proteins. In the present study, we found that all seven 14-3-3 isoforms
      were detected in the kidney inner medulla. However, only the 14-3-3 gamma-isoform
      was specifically and highly associated with UT-A1, as demonstrated by a
      glutathione-S-transferase-14-3-3 pulldown assay. The cAMP/adenylyl cyclase
      stimulator forskolin significantly enhanced their binding. Coinjection of 14-3
      3gamma cRNA into oocytes resulted in a decrease of UT-A1 function. In addition,
      14-3-3gamma increased UT-A1 ubiquitination and protein degradation. 14-3-3gamma
      can interact with both UT-A1 and mouse double minute 2, the E3 ubiquitin ligase
      for UT-A1. Thus, activation of cAMP/PKA increases 14-3-3gamma interactions with
      UT-A1 and stimulates mouse double minute 2-mediated UT-A1 ubiquitination and
      degradation, thereby forming a novel regulatory mechanism of urea transport
      activity. 

PMID- 25995114
TI  - Reviewer's comment concerning "CT morphometry of adult thoracic intervertebral
      discs" by Justin G. R. Fletcher et al. (Eur Spine J, 2015; doi:10.1007/s00586-015
      3925-y).

PMID- 25995115
TI  - Single-molecule imaging of a three-component ordered actin disassembly mechanism.
AB  - The mechanisms by which cells destabilize and rapidly disassemble filamentous
      actin networks have remained elusive; however, Coronin, Cofilin and AIP1 have
      been implicated in this process. Here using multi-wavelength single-molecule
      fluorescence imaging, we show that mammalian Cor1B, Cof1 and AIP1 work in concert
      through a temporally ordered pathway to induce highly efficient severing and
      disassembly of actin filaments. Cor1B binds to filaments first, and dramatically
      accelerates the subsequent binding of Cof1, leading to heavily decorated,
      stabilized filaments. Cof1 in turn recruits AIP1, which rapidly triggers severing
      and remains bound to the newly generated barbed ends. New growth at barbed ends
      generated by severing was blocked specifically in the presence of all three
      proteins. This activity enabled us to reconstitute and directly visualize single
      actin filaments being rapidly polymerized by formins at their barbed ends while
      simultanteously being stochastically severed and capped along their lengths, and
      disassembled from their pointed ends. 

PMID- 25995116
TI  - Food intake survey of kindergarten children in Korea: Part 1 food, energy, and
      nutrient intake.
AB  - OBJECTIVES: Nutrient intakes of children were surveyed at the time when a nation
      wide shift took place in the Republic of Korea from agriculture-based to
      industrialized society. Taking advantage of the survey locations (see below),
      possible delay in nutritional improvement in rural areas (as compared with that
      in an urban area) was also examined. METHODS: In total, 108 4- to 6-year-old
      children (boys and girls in combination) in 4 kindergartens (KGs; 1 in Seoul and
      3 in Jeju Island) participated in the survey in 2003-2004. 24-h food duplicate
      samples were prepared by the mother of each child. Food items in each duplicate
      sample were separated and coded with reference to the Dietary Reference Intake
      for Koreans (the 2005 version). Nutrient intake of the day was estimated from the
      code and weight followed by summation for daily intake. RESULTS: The children in
      the KG in Seoul studied were younger, and therefore were smaller in body size
      than those in other KGs. Thus, it was considered necessary to evaluate nutrient
      intake not only on a daily basis, but after adjustment for body weight. The AM
      daily intake of energy (protein in parenthesis) for the 108 children was 1479
      kcal (55 g)/day or 69.8 kcal (2.6 g)/kg body weight/day. Evaluation by individual
      nutrient suggested that the intake was sufficient for almost all nutrients except
      for sodium and potassium. Sodium and potassium intake (2285 and 1840 mg/day,
      respectively) was in excess and insufficient, respectively, with potential risk
      of inducing hypertension later in life. CONCLUSIONS: Inter-KG difference was not
      remarkable and therefore urban-rural difference was not apparent. Nutrient
      intakes as a whole appeared to be sufficient urban and rural areas. Nevertheless,
      excess Na intake coupled with insufficient K intake was a common problem.

PMID- 25995117
TI  - Food intake survey of kindergarten children in Korea: Part 2 increased dietary
      intake of tin possibly associated with canned foods.
AB  - OBJECTIVES: Dietary intake of tin (Sn) may be increased in some children in
      kindergartens in Korea. The present study was intended to examine this
      possibility and clarify the extent of the elevation. METHODS: 24-hour food
      duplicate and spot urine samples were collected in 2003-2004 from 108 4-6-year
      old children (boys and girls combined) in 4 kindergartens (1 in Seoul and 3 in
      Jeju Island), as reported in a previous publication. These samples were employed
      in the present analyses to examine tin levels in the diet (including beverages)
      (Sn-D). A portion of the samples were wet-ashed, and the liquid samples were
      analyzed for Sn by the ICP-MS method. For statistical evaluation, chi (2) method
      and Smirnov's test for extreme value were used. RESULTS: Sn-D in the 108 cases
      distributed as extremely biased, and could be divided into two groups, i.e.,
      those with <10 MUg Sn/day (accounting for 90% of the cases), and those with >10
      MUg/day (for 10%). Sn-D in the former group was distributed quasi-normally with
      an AM (median) of 2.9 (2.5) MUg/day. The maximum in the latter group was 3012
      MUg/day. No correlation was detected between Sn-D and Sn in urine (Sn-U).
      Comparison of the findings with published articles strongly suggested that the
      high Sn-D was due to consumption of foods (including beverages) preserved in tin
      plated cans. No positive confirmation was however possible due to insufficient
      information on food records. CONCLUSIONS: About 10% of children surveyed had
      elevated Sn-D (up to 3 mg/day). It was quite possible that high Sn-D was
      associated with tin-canned food intake.

PMID- 25995118
TI  - Food intake survey of kindergarten children in Korea: Part 3 cadmium and lead
      burden.
AB  - OBJECTIVES: This study was initiated to elucidate the extent of dietary exposure
      of children in Korea to two pollutant metals of cadmium (Cd) and lead (Pb).
      Possible urban-rural difference was also examined. METHODS: Food duplicate and
      morning spot urine samples were collected from 108 children in 4 kindergartens
      (KG) (1 KG in Seoul and 3 KGs in Jeju Island), as reported in a previous
      publication. The samples were analyzed for Cd and Pb by ICP-MS. RESULTS: Cd and
      Pb in food duplicate and urine samples were distributed approximately log
      normally. Geometric means for Cd and Pb in food duplicate samples were 12.4 and
      5.8 MUg/day, or 0.58 and 0.27 MUg/kg body weight/day, respectively, and the
      values for Cd and Pb in urine (as observed, i.e., with no correction for urine
      density) were 0.91 and 1.64 MUg/L, respectively. 2.41 and 0.30 MUg/day of Cd and
      Pb (accounting for 19.5 and 5.1%) came from boiled rice, the staple food. The
      levels of Cd and Pb burden among the children in the present survey were
      essentially the same with the levels reported for children in Pusan. The reasons
      for difference in the rank in Cd-D and Cd-U among the 4 KGs need further study.
      CONCLUSIONS: The observed levels of Cd and Pb exposure were more or less similar
      to what were reported for children in Pusan. No apparent urban-rural difference
      could be detected.

PMID- 25995120
TI  - [Therapeutic procedure of a complicated septic epiphyseal osteomyelitis in a
      heifer. A case report].
AB  - A 19-month-old Holstein-Friesian heifer displayed a circular swelling at the
      distal metacarpal area of the left forelimb with a compact, partially slightly
      fluctuating consistency. The animal exhibited no weight bearing of the affected
      limb. Radiological examinations of the fetlock area revealed a physeal
      osteomyelitis of the metacarpus. Surgical treatment involved a complete resection
      of the epiphyseal plate using a trephine. After immobilisation using a cast and
      repeated debridement of the wound cavities, the heifer was discharged with a
      slight lameness after 10 weeks. Half a year after surgical intervention no
      lameness was visible. 

PMID- 25995119
TI  - The diagnosis and management of inpatient hyponatraemia and SIADH.
AB  - BACKGROUND: Hyponatraemia is a very common medical condition that is associated
      with multiple poor clinical outcomes and is often managed suboptimally because of
      inadequate assessment and investigation. Previously published guidelines for its
      management are often complex and impractical to follow in a hospital environment,
      where patients may present to divergent specialists, as well as to generalists.
      DESIGN: A group of senior, experienced UK clinicians, met to develop a practical
      algorithm for the assessment and management of hyponatraemia in a hospital
      setting. The latest evidence was discussed and reviewed in the light of current
      clinical practicalities to ensure an up-to-date perspective. An algorithm was
      largely developed following consensus opinion, followed up with subsequent
      additions and amendments that were agreed by all authors during several rounds of
      review. RESULTS: We present a practical algorithm which includes a breakdown of
      the best methods to evaluate volume status, simple assessments for the diagnosis
      of the various causes and a straightforward approach to treatment to minimise
      complexity and maximise patient safety. CONCLUSION: The algorithm we have
      developed reflects the best available evidence and extensive clinical experience
      and provides practical, useable guidance to improve patient care.

PMID- 25995121
TI  - SPS: A Simulation Tool for Calculating Power of Set-Based Genetic Association
      Tests.
AB  - Set-based association tests, combining a set of single-nucleotide polymorphisms
      into a unified test, have become important approaches to identify weak-effect or
      low-frequency risk loci of complex diseases. However, there is no comprehensive
      and user-friendly tool to estimate power of set-based tests for study design. We
      developed a simulation tool to estimate statistical power of multiple
      representative set-based tests (SPS). SPS has a graphic interface to facilitate
      parameter settings and result visualization. Advanced functions include loading
      real genotypes to define genetic architecture, set-based meta-analysis for risk
      loci with or without heterogeneity, and parallel simulations. In proof-of
      principle examples, SPS took no more than 3 sec on average to estimate the power
      in a conventional setting. The SPS has been integrated into a user-friendly
      software tool (KGG) as an independent functional module and it is freely
      available at http://statgenpro.psychiatry.hku.hk/limx/kgg/. 

PMID- 25995122
TI  - Bioinformatical analysis of the sequences, structures and functions of fungal
      polyketide synthase product template domains.
AB  - The product template (PT) domains, specifically in fungal non-reducing polyketide
      synthases (NR-PKSs), mediate the regioselective cyclization of polyketides
      dominating the final structures. However, up to date, the systematic knowledge
      about PT domains has been insufficient. In present study, the relationships
      between sequences, structures and functions of the PT domains were analyzed with
      661 NR-PKS sequences. Based on the phylogenetic analysis, the PT domains were
      classified into prominent eight groups (I-VIII) corresponding with the
      representative compounds and cyclization regioselectivity (C2-C7, C4-C9, and C6
      C11). Most of the cavity lining residue (CLR) sites in all groups were common,
      while the regional CLR site mutations resulted in the appearance of finger-like
      regions with different orientation. The cavity volumes and shapes, even the
      catalytic dyad positions of PT domains in different groups were corresponding
      with characteristic cyclization regioselectivity and compound sizes. The
      conservative residues in PT sequences were responsible for the cyclization
      functions and the evolution of the key residues resulted in the differentiations
      of cyclization functions. The above findings may help to better understand the
      cyclization mechanisms of PT domains and even predict the structural types of the
      aromatic polyketide products. 

PMID- 25995123
TI  - Constructs of depression and distress in diabetes: time for an appraisal.
AB  - Depression presents in roughly 20% of people with diabetes worldwide, and
      adversely affects quality of life and treatment outcomes. The causes of
      depression in diabetes are poorly understood, but research suggests a bi
      directional association, at least for type 2 diabetes. Inconsistent findings
      regarding prevalence and depression treatment outcomes in patients with diabetes
      seem partly attributable to inconsistencies in the definition and measurement of
      depression and in distinguishing it from diabetes-distress, a psychological
      concept related to depression. We review evidence suggesting that diabetes
      distress and depression are correlated and overlapping constructs, but are not
      interchangeable. Importantly, diabetes-distress seems to mediate the association
      between depression and glycaemic control. We propose a model to explain the
      direct and indirect effects of depression and diabetes-distress on glycaemic
      control. Additionally, using emerging insights from data-driven approaches, we
      suggest three distinct symptom profiles to define depression in patients with
      diabetes that could help explain differential associations between depression and
      metabolic abnormalities, and to tailor interventions for depression. Future
      research should focus on further refining depression profiles in patients with
      diabetes, taking into account the natural history of diabetes and depression,
      clinical characteristics, and diabetes-distress. The assessment of diabetes
      distress and depression in research and clinical practice will be essential to
      identify high-risk patients with different mental health needs. 

PMID- 25995124
TI  - The link between depression and diabetes: the search for shared mechanisms.
AB  - Depression is twice as common in people with type 1 or type 2 diabetes as in the
      general population, and is associated with poor outcomes. Evidence is growing
      that depression and type 2 diabetes share biological origins, particularly
      overactivation of innate immunity leading to a cytokine-mediated inflammatory
      response, and potentially through dysregulation of the hypothalamic-pituitary
      adrenal axis. Throughout the life course, these pathways can lead to insulin
      resistance, cardiovascular disease, depression, increased risk of type 2
      diabetes, and increased mortality. Proinflammatory cytokines might directly
      affect the brain, causing depressive symptoms. In type 1 diabetes, mediators of
      depression are not well studied, with research hindered by inconsistent
      definitions of depression and scarcity of observational, mechanistic, and
      interventional research along the life course. Despite few studies, evidence
      suggests that familial relationships and burden of a lifelong disorder with an
      onset early in personality development might contribute to increased
      vulnerability to depression. Overall, longitudinal research is needed to identify
      risk factors and mechanisms for depression in patients with diabetes,
      particularly early in the life course. Ultimately, improved understanding of
      shared origins of depression and diabetes could provide the potential to treat
      and improve outcomes of both disorders simultaneously. These shared origins are
      targets for primary prevention of type 2 diabetes. 

PMID- 25995125
TI  - Depression and diabetes: treatment and health-care delivery.
AB  - Despite research efforts in the past 20 years, scientific evidence about
      screening and treatment for depression in diabetes remains incomplete and is
      mostly focused on North American and European health-care systems. Validated
      instruments to detect depression in diabetes, although widely available, only
      become effective and thus recommended if subsequent treatment pathways are
      accessible, which is often not the case. Because of the well known adverse
      effects of the interaction between depression and diabetes, treatment goals
      should focus on the remission or improvement of depression as well as improvement
      in glycaemic control as a marker for subsequent diabetes outcome. Scientific
      evidence evaluating treatment for depression in type 1 and type 2 diabetes shows
      that depression can be treated with moderate success by various psychological and
      pharmacological interventions, which are often implemented through collaborative
      care and stepped-care approaches. The evidence for improved glycaemic control in
      the treatment of depression by use of selective serotonin reuptake inhibitors or
      psychological approaches is conflicting; only some analyses show small to
      moderate improvements in glycaemic control. More research is needed to evaluate
      treatment of different depression subtypes in people with diabetes, the cost
      effectiveness of treatments, the use of health-care resources, the need to
      account for cultural differences and different health-care systems, and new
      treatment and prevention approaches. 

PMID- 25995126
TI  - Mental health problems in young male offenders with and without sex offences: a
      comparison based on the MAYSI-2.
AB  - BACKGROUND: There is a need for better knowledge about the relationship between
      sexual offending by young people and mental health problems. AIM: This study
      aimed to compare mental health problems between young people who commit sexual
      offences and those who do not. METHODS: After completion of the Massachusetts
      Youth Screening Instrument-Version 2 (MAYSI-2), 334 young people who, according
      to MAYSI-2 information, had committed a sex offence were compared with 334 young
      people whose MAYSI-2 data suggested that they had not committed a sex offence.
      They were matched for age, race/ethnicity, type of facility and adjudication
      status. We also examined the young sex offenders for within group differences.
      RESULTS: The young sex offenders were less likely to report anger-irritability or
      substance misuse than the comparison youths. Within the sex offender group, older
      juveniles were more likely to report alcohol and drug use problems than younger
      ones, Caucasians were more likely to report anger and suicidal ideation than
      their non-Caucasian peers, those detained were more likely to report alcohol and
      drug use problems and somatic complaints than those on probation, and convicted
      youths were more likely to report alcohol and drug use problems and anger
      irritability than those awaiting trial. CONCLUSIONS: Juvenile sexual offending
      seems less likely to be committed in the context of an anti-social lifestyle than
      other offending. Important findings among young sex offenders are their higher
      levels of mental health problems among those detained and convicted than among
      those on probation or awaiting trial. Assessment of the mental health of young
      sex offenders seems to be even more important the further they are into the
      justice system. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25995127
TI  - Developmental toxicity and endocrine disruption of naphthenic acids on the early
      life stage of zebrafish (Danio rerio).
AB  - Oil sands process-affected water (OSPW) has been reported to exhibit adverse
      effects on the environment and wildlife. Although the compounds responsible are
      unknown, naphthenic acids (NAs) have been considered to be implicated. The
      current study was designed to investigate whether NAs might cause developmental
      toxicity and endocrine disruption on the early life stage of zebrafish (Danio
      rerio). The success of embryo hatch was inhibited by 2.5 mg l(-1) oil sands NAs
      (OS-NAs) exposure, and both OSPW NAs and commercial NAs (C-NAs) exposure resulted
      in a variety of developmental lesions in the fish larvae, such as yolk sac edema,
      pericardial edema and spinal malformation. The transcription of genes involved
      cytochrome P450 aromatase (CYP19a and CYP19b), estrogen receptors (ERalpha,
      ERbeta1 and ERbeta2), and vitellogenin (VTG) was analyzed to evaluate the
      endocrine disrupting effects of NAs. Significant up-regulated gene expressions of
      CYP19b, ERalpha and VTG were observed in both OS-NAs and C-NAs groups, which
      indicated the deleteriously estrogenic potential of NAs. These results confirmed
      that NAs derived from crude petroleum could negatively impact the development and
      endocrine function of zebrafish, and be primarily responsible for the toxicity of
      OSPW.

PMID- 25995128
TI  - [2015 Springer Prize for Dermatology].

PMID- 25995129
TI  - Let's not forget climate change in the food insecurity conversation: why the
      homeless are most vulnerable.

PMID- 25995130
TI  - Cost-Effectiveness of Proton Pump Inhibitor Co-Therapy in Patients Taking Aspirin
      for Secondary Prevention of Ischemic Stroke.
AB  - BACKGROUND: Low-dose aspirin (ASA) is effective for secondary prevention of
      ischemic stroke but can increase the risks of hemorrhagic stroke, upper
      gastrointestinal bleeding (UGIB), and dyspepsia. Prophylactic administration of
      proton pump inhibitors (PPIs) reduces the risks of these digestive symptoms. We
      investigated the cost effectiveness of adding a PPI to ASA therapy for ischemic
      stroke patients in Japan. METHODS: A Markov state-transition model was developed
      to compare the cost effectiveness of ASA monotherapy with ASA plus PPI co-therapy
      in patients with histories of upper gastrointestinal ulcers and ischemic stroke.
      The model takes into account ASA adherence rate and adverse effects due to ASA,
      including hemorrhagic stroke and UGIB. The analysis was performed from the
      perspective of healthcare payers in 2013. RESULTS: In the base case, total life
      years by PPI co-therapy and monotherapy were 16.005 and 15.932, respectively. The
      difference in duration of no therapy (no ASA or PPI) between the therapies was
      558.5 days, which would prevent 30.3 recurrences of ischemic stroke per 1000
      person-years. The incremental cost-effectiveness ratio of PPI co-therapy relative
      to monotherapy was Y1,191,665 (US$11,458) per life-year gained. In a one-way
      sensitivity analysis, PPI co-therapy was consistently cost effective at a
      willingness to pay of Y5,000,000 (US$48,077) per life-year gained. In a
      probabilistic sensitivity analysis, the probability that PPI co-therapy was cost
      effective was 89.74% at the willingness to pay. CONCLUSIONS: Co-therapy with ASA
      plus PPI appears to be cost-effective compared with ASA monotherapy. The addition
      of PPI also appeared to prolong the duration of ASA therapy, thereby reducing the
      risk of ischemic stroke.

PMID- 25995132
TI  - Is self-reported adherence associated with clinical outcomes in women treated
      with anticholinergic medication for overactive bladder?
AB  - AIM: To determine the association between self-reported adherence to
      anticholinergic medication and clinical outcomes in women with overactive bladder
      (OAB). METHODS: A prospective study of women with OAB treated with fesoterodine
      for 8 weeks. Adherence to medication was measured using the Medication Adherence
      Self-report Inventory (MASRI). A self reported adherence rate of >=80% was
      considered adherent. The association between self-reported adherence and clinical
      outcomes (Global Index of Improvement, Global impression of Severity, urinary
      symptom and quality of life scores) was examined. We hypothesized that adherent
      women would have greater improvement in urinary symptoms and quality of life than
      non-adherent women. RESULTS: Based on the MASRI, 115 (62.5%) women were adherent
      and 69 (37.5%) were non-adherent to anticholinergic medication at 8weeks.
      Adherent women were more likely to report overall improvement in their symptoms
      compared to non-adherent women (84% vs. 24%, P < 0.001). Significantly more non
      adherent women described their bladder symptoms as "moderate" or "severe" at 8
      weeks compared to adherent women (74% vs. 44%, P = 0.03). At 8 weeks, adherent
      women reported significantly greater improvement (change) in urinary symptoms
      from baseline to 8 weeks than non-adherent women (-13.3 +/- 25.8 vs. 2.5 +/-
      14.4, P = 0.04). Similarly, adherent women reported greater improvement in
      quality of life scores than non-adherent women (- 7.9 +/- 24.0 vs. -1.8 +/- 11.9,
      P = 0.003). CONCLUSION: Self-reported non-adherence, as measured by the MASRI, is
      associated with clinically meaningful outcomes in women with OAB. This further
      validates the MASRI as a clinically useful tool for measuring adherence to
      anticholinergic medications in women with OAB. Neurourol. Urodynam. 35:738-742,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25995131
TI  - Chronic kidney disease is associated with a higher 90-day mortality than other
      chronic medical conditions in patients with sepsis.
AB  - According to previous studies, the clinical course of sepsis could be affected by
      preexisting medical conditions, which are very common among patients with sepsis.
      This observational study aimed at investigating whether common chronic medical
      conditions affect the 90-day mortality risk in adult Caucasian patients with
      sepsis. A total of 482 patients with sepsis were enrolled in this study. The
      ninety-day mortality was the primary outcome; organ failure was the secondary
      outcome. Sepsis-related organ failure assessment (SOFA) scores and the
      requirements for organ support were evaluated to assess organ failure. A
      multivariate Cox regression model for the association between the 90-day
      mortality risk and chronic preexisting medical conditions adjusted for all
      relevant confounders and mortality predictors revealed the highest hazard ratio
      for patients with chronic kidney disease (CKD) (hazard ratio, 2.25; 95% CI, 1.46
      3.46; p = 0.0002). Patients with CKD had higher SOFA scores than patients without
      CKD (8.9 +/- 4.0 and 6.5 +/- 3.4, respectively; p < 0.0001). Additionally, an
      analysis of organ-specific SOFA scores revealed higher scores in three organ
      systems (kidney, cardiovascular and coagulation). Patients with CKD have the
      highest 90-day mortality risk compared with patients without CKD or with other
      chronic medical conditions.

PMID- 25995133
TI  - Does metabosensitive afferent fibers activity differ from slow- and fast-twitch
      muscles?
AB  - This study was designed to investigate the metabosensitive afferent response
      evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium
      chloride (KCl) in three muscle types. We recorded the activity of groups III-IV
      afferents originating from soleus, gastrocnemius and tibialis anterior muscles.
      Our data showed a same pattern of response in the three muscles after chemical
      injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA
      injections and a linear relationship between KCl concentrations and the afferent
      discharge rate. Furthermore, a stronger response was recorded after EIF in the
      gastrocnemius muscle compared to the two other muscles. The change in afferent
      discharge after 1 mM LA injection was higher for the gastrocnemius muscle
      compared to the response obtained with the corresponding concentration applied in
      the two other muscles, whereas changes to KCl injections did not dramatically
      differ between the three muscles. We conclude that anatomical (mass, phenotype,
      vascularization, receptor and afferent density...) and functional (flexor vs.
      extensor) differences between muscles could explain the amplitude of these
      responses.

PMID- 25995134
TI  - Autonomic and brain responses associated with empathy deficits in autism spectrum
      disorder.
AB  - Accumulating evidence suggests that autonomic signals and their cortical
      representations are closely linked to emotional processes, and that related
      abnormalities could lead to social deficits. Although socio-emotional impairments
      are a defining feature of autism spectrum disorder (ASD), empirical evidence
      directly supporting the link between autonomic, cortical, and socio-emotional
      abnormalities in ASD is still lacking. In this study, we examined autonomic
      arousal indexed by skin conductance responses (SCR), concurrent cortical
      responses measured by functional magnetic resonance imaging, and effective brain
      connectivity estimated by dynamic causal modeling in seventeen unmedicated high
      functioning adults with ASD and seventeen matched controls while they performed
      an empathy-for-pain task. Compared to controls, adults with ASD showed enhanced
      SCR related to empathetic pain, along with increased neural activity in the
      anterior insular cortex, although their behavioral empathetic pain
      discriminability was reduced and overall SCR was decreased. ASD individuals also
      showed enhanced correlation between SCR and neural activities in the anterior
      insular cortex. Importantly, significant group differences in effective brain
      connectivity were limited to greater reduction in the negative intrinsic
      connectivity of the anterior insular cortex in the ASD group, indicating a
      failure in attenuating anterior insular responses to empathetic pain. These
      results suggest that aberrant interoceptive precision, as indexed by
      abnormalities in autonomic activity and its central representations, may underlie
      empathy deficits in ASD.

PMID- 25995135
TI  - Therapeutic role of ultrasound-guided intranodal lymphangiography in refractory
      cervical chylous leakage after neck dissection: Report of a case and review of
      the literature.
AB  - BACKGROUND: Chylous leakage is a well-recognized but rare complication of head
      and neck surgery, affecting approximately 1% to 2.5% of head and neck
      dissections. It is a potentially life-threatening condition characterized by
      electrolyte imbalance, immunosuppression, delayed wound healing, risk of
      infection, and generalized sepsis. Management can be problematic and prolonged.
      METHODS: We present a case of refractory cervical chylous leakage after neck
      dissection treated with ultrasound-guided intranodal lymphangiography. RESULTS:
      Ultrasound-guided intranodal lymphangiography alone resulted in rapid and
      complete resolution of chylous leakage with minimal morbidity. CONCLUSION: Based
      on our clinical experience and after a thorough literature review, we propose
      that ultrasound-guided intranodal lymphangiography with contrast agent could be
      considered a viable therapeutic option for persistent chylous leakages in
      selected patients.

PMID- 25995137
TI  - Assessment of the physicochemical and microbiological status of western Niger
      Delta soil for crude oil pollution bioremediation potential.
AB  - The physical, chemical and microbiological characteristics of the soil across the
      western Niger Delta area of Nigeria were determined to assess its potential for
      natural remediation of crude oil pollution. The pH (oil-producing area, 6.1 +/-
      1.1; non-oil producing, 5.9 +/- 0.9) and temperature (28-35  degrees C in both
      areas) were favourable to natural remediation, while the fluctuating moisture
      (7.7-45.6 %) and the dominant sandy soil textural classes (70 %) were
      limitations. The carbon nitrogen phosphorus (CNP) ratio markedly exceeded
      recommended 100:10:1, while the cation exchange capacity was below acceptable
      range. Counts of heterotrophic bacteria, fungi and hydrocarbon-utilising and
      nitrogen-fixing bacteria (mean range log10 3.8 +/- 1.5-6.52 +/- 0.9 cfu/g) were
      favourable having markedly exceeded the minimum counts required. Crude oil loss
      was highest in loam soil, but significantly (P = 0.00) increased in all soil
      textural classes including sandy soils after amendment with cow dung/poultry
      dropping and manual aeration in laboratory and 8-month field tests as indicated
      by two-way ANOVA. Thus, the overall assessment is that while CNP can be viewed as
      the major limiting factor to natural oil pollution remediation in the western
      Niger Delta soil, its influence can be minimised by the amendment indicated in
      the study.

PMID- 25995138
TI  - The effects of China's environmental protection policies on pasture quality and
      the activities of small-scale herders in Songpan County, Western Sichuan.
AB  - Since 2000, there has been an ambitious governmental effort to protect China's
      grassland resources through new, often controversial, policies and programs
      backed up by massive capital investments and subsidies. The policies are intended
      to protect pastoral ecological systems while allowing the pasture-based husbandry
      sector to continue to evolve in ways that assure acceptable revenues to affected
      families and regions. This article reports results of a case study conducted in
      Songpan County of western Sichuan during the fall of 2013 specifically focused on
      these issues and interactions. The mixed-method research combines remotely sensed
      MODIS vegetation indices (EVI), livestock counts by type, and grassland area
      estimates at the township scale from 2000-2012, with depth interviews with local
      herding families and husbandry officials to determine how the husbandry sector
      has changed in the past 12 years under post-2000 policy interventions. Results
      for Songpan indicate that pasture coverage has improved slightly as grazing
      livestock density per hectare declined, but herders and local officials report
      that some of the new laws and programs have important unanticipated negative
      impacts on pasture quality, pasture ecology, and economic returns from herding
      for some families.

PMID- 25995139
TI  - Water quality monitoring of Al-Habbaniyah Lake using remote sensing and in situ
      measurements.
AB  - The use of remote sensing and GIS in water monitoring and management has been
      long recognized. This paper, however discusses the application of remote sensing
      and GIS specifically in monitoring water quality parameters in Al-Habbaniyah
      Lake, and the results were compared with in situ measurements. Variations of
      different parameters under investigation were as follows: temperature (15-33
      degrees C), pH (7-9), dissolved oxygen (6-11 mg/L), BOD5 (0.5-1.8), electrical
      conductivity (200-2280 MUS/cm), TDS (147-1520 mg/L), TSS (68-3200), turbidity (5
      51), nitrate (0.7-20 mg/l), phosphate (77-220 MUg/l), and chlorophyll-a (0.9-130
      MUg/l). Remote sensing results revealed that the band 5 was most likely
      significantly correlated with turbidity in the winter. Band 2 and 3 was most
      likely significantly correlated with TDS in autumn and summer, while band 2 was
      most likely significantly correlated with TSS in autumn, band 2 is most likely
      significantly correlated with chlorophyll-a in autumn. The current study results
      demonstrated convergence between in situ and remote sensing readings. The models
      were used to explore the values of each of chlorophyll-a, TSS,TDS, and turbidity
      did not deviate much from the values actually measured in the three seasons.
      Nevertheless, they were very useful in anticipating all seasons of the study due
      to the insignificant deviation between the remotely sensed values and actual
      measured values.

PMID- 25995140
TI  - Silks as scaffolds for skin reconstruction.
AB  - In this short review, we describe the use of high molecular weight proteins
      produced in the glands of several arthropods-commonly called silks-for the
      purpose to enhance human skin wound healing. To this end an extensive literature
      search has been performed, the publications have been categorized concerning silk
      preparation and application and summarized accordingly: Scaffolds to promote
      wound healing were prepared by processing the silks in different ways including
      solubilization of the protein fibers followed by casting or electrospinning. The
      silk scaffolds were additionally modified by coating or blending with the
      intention of further functionalization. In several approaches, the scaffolds were
      also vitalized with skin cells or stem cells. In vitro and in vivo models were
      implied to test for safety and efficiency. We conclude that silk scaffolds are
      characterized by an advantageous biocompatibility as well as an impressive
      versatility rendering them ideally suited for application in wounds.
      Nevertheless, further investigation is needed to exploit the full capacity of
      silk in different wound models and to achieve clinical transfer in time.

PMID- 25995141
TI  - "Click" post-functionalization of a metal-organic framework for engineering
      active single-site heterogeneous Ru(iii) catalysts.
AB  - We present a general strategy for incorporating pi-conjugated NNN-chelators
      (e.g., terpyridyl moiety) into a porous metal-organic framework (MOF) MIL-101(Cr)
      by using the "click" post-functionalization. The functionalized MOF could be used
      as a platform for metalation to yield highly active and stable single-site
      heterogeneous metal (e.g., Ru(iii)) catalysts. 

PMID- 25995142
TI  - Minimally invasive renal autotransplantation.
AB  - Minimally invasive renal allotransplantation techniques have been recently
      described; reported benefits include reduced morbidity/complications. These
      benefits have been successfully adapted for minimally invasive renal
      autotransplantation, however, in a non-oncological setting. We, here, describe a
      novel alternative robot-assisted renal autotransplantation technique, utilizing
      GelPOINT, which by permitting ex vivo graft examination and surgery might allow
      further broadening of indications for minimally-invasive renal
      autotransplantation, to include complex oncological renal/ureteral lesions.
      Future studies are needed to evaluate the utility of these techniques.

PMID- 25995149
TI  - Total synthesis of (+)-gelsemine via an organocatalytic Diels-Alder approach.
AB  - The structurally complex alkaloid gelsemine was previously thought to have no
      significant biological activities, but a recent study has shown that it has
      potent and specific antinociception in chronic pain. While this molecule has
      attracted significant interests from the synthetic community, an efficient
      synthetic strategy is still the goal of many synthetic chemists. Here we report
      the asymmetric total synthesis of (+)-gelsemine, including a highly
      diastereoselective and enantioselective organocatalytic Diels-Alder reaction, an
      efficient intramolecular trans-annular aldol condensation furnishing the
      prolidine ring and establishing the configuration of the C20 quaternary carbon
      stereochemical centre. The entire gelsemine skeleton was constructed through a
      late-stage intramolecular SN2 substitution. The enantiomeric excess of this total
      synthesis is over 99%, and the overall yield is around 5%. 

PMID- 25995151
TI  - Laparoscopy in combination with fast-track management is the best surgical
      strategy in patients undergoing colorectal resection for cancer.

PMID- 25995150
TI  - Report of outbreaks of classical scrapie in Dorper sheep and associated prion
      protein gene polymorphisms in affected flocks.
AB  - Scrapie is an infectious neurodegenerative disease affecting sheep and goats,
      related with conformational alteration of an isoform of the prion protein that
      leads to deposition and aggregation in the host's central nervous system.
      Occurrence of the natural disease can be influenced by host genetic factors, such
      as a single nucleotide polymorphism of the prion protein gene. This study reports
      three scrapie-affected Dorper flocks located on three different farms in Brazil.
      The objective of this study was to analyze these three flocks using scrapie
      diagnostics, combining histology, immunohistochemistry, genotyping, and western
      blot assays. For immunohistochemistry, 192 sheep were selected and 308 sheep
      blood samples were taken for genotyping. A total of 22 sheep were scrapie
      positive by immunohistochemistry. Of these, four presented clinical signs and had
      scrapie immunoreactivity at the obex in western blot assays. The sheep without
      clinical signs were positive in lymphoid organs, such as the third eyelid and
      rectal mucosa. The major genotypes found on the flocks were ARQ/ARQ, ARQ/ARR, and
      ARQ/VRQ for codons 136, 154, and 171. Most of the sheep were considered to be at
      moderate to high risk, based on risk groups for developing scrapie. Some blood
      samples were sequenced, and polymorphisms were identified in other codons, such
      as 127, 142, and 143. Our data demonstrate the importance of preclinical scrapie
      diagnosis in Brazilian sheep, as most of the affected sheep showed no clinical
      signs, and emphasize the relevance of genotyping other Dorper sheep to determine
      the genotypic profile of the breed. 

PMID- 25995152
TI  - Concomitant use of polarization and positive phase contrast microscopy for the
      study of microbial cells.
AB  - Polarization and positive phase contrast microscope were concomitantly used in
      the study of the internal structure of microbial cells. Positive phase contrast
      allowed us to view even the fine cell structure with a refractive index
      approaching that of the surrounding environment, e.g., the cytoplasm, and
      transferred the invisible phase image to a visible amplitude image. With
      polarization microscopy, crossed polarizing filters together with compensators
      and a rotary stage showed the birefringence of different cell structures.
      Material containing algae was collected in ponds in Sykorice and Zbecno villages
      (Krivoklat region). The objects were studied in laboratory microscopes LOMO MIN-8
      Sankt Petersburg and Polmi A Carl Zeiss Jena fitted with special optics for
      positive phase contrast, polarizers, analyzers, compensators, rotary stages, and
      digital SLR camera Nikon D 70 for image capture. Anisotropic granules were found
      in the cells of flagellates of the order Euglenales, in green algae of the orders
      Chlorococcales and Chlorellales, and in desmid algae of the order Desmidiales.
      The cell walls of filamentous algae of the orders Zygnematales and Ulotrichales
      were found to exhibit significant birefringence; in addition, relatively small
      amounts of small granules were found in the cytoplasm. A typical shape-related
      birefringence of the cylindrical walls and the septa between the cells differed
      in intensity, which was especially apparent when using a Zeiss compensator RI-c
      during its successive double setting. In conclusion, the anisotropic granules
      found in the investigated algae mostly showed strong birefringence and varied in
      number, size, and location of the cells. Representatives of the order
      Chlorococcales contained the highest number of granules per cell, and the size of
      these granules was almost double than that of the other monitored microorganisms.
      Very strong birefringence was exhibited by cell walls of filamentous algae; it
      differed in the intensity between the cylindrical peripheral wall and the
      partitions between the cells. Positive phase contrast enabled us to study the
      morphological relationship of various fine structures in the cell (poorly visible
      in conventional microscope) to anisotropic structures that have been well defined
      by polarization microscopy. 

PMID- 25995153
TI  - Explicit Modeling of Ancestry Improves Polygenic Risk Scores and BLUP Prediction.
AB  - Polygenic prediction using genome-wide SNPs can provide high prediction accuracy
      for complex traits. Here, we investigate the question of how to account for
      genetic ancestry when conducting polygenic prediction. We show that the accuracy
      of polygenic prediction in structured populations may be partly due to genetic
      ancestry. However, we hypothesized that explicitly modeling ancestry could
      improve polygenic prediction accuracy. We analyzed three GWAS of hair color (HC),
      tanning ability (TA), and basal cell carcinoma (BCC) in European Americans
      (sample size from 7,440 to 9,822) and considered two widely used polygenic
      prediction approaches: polygenic risk scores (PRSs) and best linear unbiased
      prediction (BLUP). We compared polygenic prediction without correction for
      ancestry to polygenic prediction with ancestry as a separate component in the
      model. In 10-fold cross-validation using the PRS approach, the R(2) for HC
      increased by 66% (0.0456-0.0755; P < 10(-16)), the R(2) for TA increased by 123%
      (0.0154 to 0.0344; P < 10(-16)), and the liability-scale R(2) for BCC increased
      by 68% (0.0138-0.0232; P < 10(-16)) when explicitly modeling ancestry, which
      prevents ancestry effects from entering into each SNP effect and being
      overweighted. Surprisingly, explicitly modeling ancestry produces a similar
      improvement when using the BLUP approach, which fits all SNPs simultaneously in a
      single variance component and causes ancestry to be underweighted. We validate
      our findings via simulations, which show that the differences in prediction
      accuracy will increase in magnitude as sample sizes increase. In summary, our
      results show that explicitly modeling ancestry can be important in both PRS and
      BLUP prediction.

PMID- 25995154
TI  - Polyethylene Glycol Coatings on Plastic Substrates for Chemically Defined Stem
      Cell Culture.
AB  - Human mesenchymal stem cells (hMSCs) are a widely available and clinically
      relevant cell type with a host of applications in regenerative medicine. Current
      clinical expansion methods can lead to selective changes in hMSC phenotype
      potentially resulting from relatively undefined cell culture surfaces. Chemically
      defined synthetic surfaces can aid in understanding the influence of cell
      material interactions on stem cell behavior. Here, a thin copolymer coating for
      hMSC culture on plastic substrates is developed. The random copolymer is
      synthesized by living free radical polymerization and characterized in solution
      before application to the substrate, ensuring a homogeneous coating and limiting
      the sample-to-sample variations. The ability to coat multiple substrate types and
      cover large surface areas is reported. Arg-Gly-Asp-containing peptides are
      incorporated into the coating under aqueous conditions via their lysine or
      cysteine side chains, resulting in amide and thioester linkages, respectively.
      Stability studies show amide linkages to be stable and thioester linkages to be
      labile under standard serum-containing culture conditions. In addition,
      chemically defined passaging of hMSCs using only ethylenediaminetetraacetic acid
      on polystyrene dishes is shown. After passage, the hMSCs can be seeded back onto
      the same plate, indicating potential reusability of the coating. 

PMID- 25995155
TI  - Non-coding RNAs in the pathogenesis of COPD.
AB  - A large part of the human genome is transcribed in non-coding RNAs, transcripts
      that do not code for protein, including microRNAs (miRNAs) and long non-coding
      RNAs (lncRNAs). MiRNAs are short single-stranded RNA molecules that negatively
      regulate gene expression at the post-transcriptional level. They play an
      important regulatory role in many biological processes. Consequently, altered
      expression of these non-coding RNAs has been shown to lead to inflammation and
      disease. In contrast, lncRNAs, can both enhance or repress the expression of
      protein-coding genes. COPD is typically caused by tobacco smoking and leads to a
      progressive decline in lung function and a premature death. Exaggerated pulmonary
      inflammation is a hallmark feature in this disease, leading to obstructive
      bronchiolitis and emphysema. In this review, we discuss the miRNA expression
      patterns in lungs of patients with COPD and in mouse models and we highlight
      various miRNAs involved in COPD pathogenesis. In addition, we briefly discuss a
      specific lncRNA that is upregulated upon cigarette smoke exposure, providing a
      short introduction to this more recently discovered group of non-coding RNAs. 

PMID- 25995156
TI  - Tiotropium attenuates IL-13-induced goblet cell metaplasia of human airway
      epithelial cells.
AB  - BACKGROUND: It has been shown that acetylcholine is both a neurotransmitter and
      acts as a local mediator, produced by airway cells including epithelial cells. In
      vivo studies have demonstrated an indirect role for acetylcholine in epithelial
      cell differentiation. Here, we aimed to investigate direct effects of endogenous
      non-neuronal acetylcholine on epithelial cell differentiation. METHODS: Human
      airway epithelial cells from healthy donors were cultured at an air-liquid
      interface (ALI). Cells were exposed to the muscarinic antagonist tiotropium (10
      nM), interleukin (IL)-13 (1, 2 and 5 ng/mL), or a combination of IL-13 and
      tiotropium, during or after differentiation at the ALI. RESULTS: Human airway
      epithelial cells expressed all components of the non-neuronal cholinergic system,
      suggesting acetylcholine production. Tiotropium had no effects on epithelial cell
      differentiation after air exposure. Differentiation into goblet cells was barely
      induced after air exposure. Therefore, IL-13 (1 ng/mL) was used to induce goblet
      cell metaplasia. IL-13 induced MUC5AC-positive cells (5-fold) and goblet cells
      (14-fold), as assessed by histochemistry, and MUC5AC gene expression (105-fold).
      These effects were partly prevented by tiotropium (47-92%). Goblet cell
      metaplasia was induced by IL-13 in a dose-dependent manner, which was inhibited
      by tiotropium. In addition, tiotropium reversed goblet cell metaplasia induced by
      2 weeks of IL-13 exposure. IL-13 decreased forkhead box protein A2 (FoxA2)
      expression (1.6-fold) and increased FoxA3 (3.6-fold) and SAM-pointed domain
      containing ETS transcription factor (SPDEF) (5.2-fold) expression. Tiotropium
      prevented the effects on FoxA2 and FoxA3, but not on SPDEF. CONCLUSIONS: We
      demonstrate that tiotropium has no effects on epithelial cell differentiation
      after air exposure, but inhibits and reverses IL-13-induced goblet cell
      metaplasia, possibly via FoxA2 and FoxA3. This indicates that non-neuronal
      acetylcholine contributes to goblet cell differentiation by a direct effect on
      epithelial cells.

PMID- 25995157
TI  - Preventing out-of-hospital asthma deaths.

PMID- 25995158
TI  - Financial Incentives and Inequalities in Smoking Cessation Interventions in
      Primary Care: Before-and-After Study.
AB  - INTRODUCTION: The Quality and Outcomes Framework (QOF) is a financial incentive
      scheme that rewards UK general practices for providing evidence-based care,
      including smoking cessation advice mainly as a secondary prevention intervention.
      We examined the effects on smoking outcomes and inequalities of a local version
      of QOF (QOF+), which ran from 2008 to 2011 and extended financial incentives to
      the provision of cessation advice as a primary prevention intervention. METHODS:
      Before-and-after study using data from 28 general practices in Hammersmith &
      Fulham, London, United Kingdom. We used logistic regression to examine changes in
      smoking outcomes associated with QOF+ within and between sociodemographic groups.
      RESULTS: Recording of smoking status increased from 55.5% to 64.3% for men (P <
      .001) and from 67.9% to 75.8% for women (P < .001). All groups benefitted from
      the increase, but younger patients remained less likely to be asked about smoking
      than older patients. White patients were less likely to be asked than those from
      other ethnic groups. Smoking cessation advice increased from 32.7% to 54.0% for
      men (P < .001) and from 35.4% to 54.1% for women (P < .01) and there was little
      variation between groups for this outcome. Recorded smoking prevalence reduced
      from 25.0% to 20.8% for men (P < .001) and from 16.1% to 12.5% for women (P <
      .001). White patients and those from more deprived areas remained more likely to
      be smokers than other groups. CONCLUSION: The introduction of QOF+ was associated
      with general improvements in recording of smoking outcomes, but inequalities in
      ascertainment and smoking prevalence with respect to age, ethnicity, and
      deprivation persisted.

PMID- 25995159
TI  - A Comparison of the Fagerstrom Test for Cigarette Dependence and Cigarette
      Dependence Scale in a Treatment-Seeking Sample of Pregnant Smokers.
AB  - INTRODUCTION: Valid and reliable brief measures of cigarette dependence are
      essential for research purposes and effective clinical care. Two widely-used
      brief measures of cigarette dependence are the six-item Fagerstrom Test for
      Cigarette Dependence (FTCD) and five-item Cigarette Dependence Scale (CDS-5).
      Their respective metric characteristics among pregnant smokers have not yet been
      studied. METHODS: This was a secondary analysis of data of pregnant smokers (N =
      476) enrolled in a smoking cessation study. We assessed internal consistency,
      reliability, and examined correlations between the instruments and smoking
      related behaviors for construct validity. We evaluated predictive validity by
      testing how well the measures predict abstinence 2 weeks after quit date.
      RESULTS: Cronbach's alpha coefficient for the CDS-5 was 0.62 and for the FTCD
      0.55. Measures were strongly correlated with each other, although FTCD, but not
      CDS-5, was associated with saliva cotinine concentration. The FTCD, CDS-5,
      craving to smoke, and withdrawal symptoms failed to predict smoking status 2
      weeks following the quit date. CONCLUSIONS: Suboptimal reliability estimates and
      failure to predict short-term smoking call into question the value of including
      either of the brief measures in studies that aim to explain the obstacles to
      smoking cessation during pregnancy.

PMID- 25995160
TI  - Nicotine Metabolism in Young Adult Daily Menthol and Nonmenthol Smokers.
AB  - INTRODUCTION: Menthol cigarette smoking may increase the risk for tobacco smoke
      exposure and inhibit nicotine metabolism in the liver. Nicotine metabolism is
      primarily mediated by the enzyme CYP2A6 and the nicotine metabolite ratio (NMR =
      trans 3' hydroxycotinine/cotinine) is a phenotypic proxy for CYP2A6 activity. No
      studies have examined differences in this biomarker among young adult daily
      menthol and nonmenthol smokers. This study compares biomarkers of tobacco smoke
      exposure among young adult daily menthol and nonmenthol smokers. METHODS: Saliva
      cotinine and carbon monoxide were measured in a multiethnic sample of daily
      smokers aged 18-35 (n = 186). Nicotine, cotinine, the cotinine/cigarette per day
      ratio, trans 3' hydroxycotinine, the NMR, and expired carbon monoxide were
      compared. RESULTS: The geometric means for nicotine, cotinine, and the
      cotinine/cigarette per day ratio did not significantly differ between menthol and
      nonmenthol smokers. The NMR was significantly lower among menthol compared with
      nonmenthol smokers after adjusting for race/ethnicity, gender, body mass index,
      and cigarette smoked per day (0.19 vs. 0.24, P = .03). White menthol smokers had
      significantly higher cotinine/cigarettes per day ratio than white nonmenthol
      smokers in the adjusted model. White menthol smokers had a lower NMR in the
      unadjusted model (0.24 vs. 0.31, P = .05) and the differences remained marginally
      significant in the adjusted model (0.28 vs. 0.34, P = .06). We did not observe
      these differences in Native Hawaiians and Filipinos. CONCLUSIONS: Young adult
      daily menthol smokers have slower rates of nicotine metabolism than nonmenthol
      smokers. Studies are needed to determine the utility of this biomarker for
      smoking cessation treatment assignments.

PMID- 25995161
TI  - Assessment of American Heart Association's Ideal Cardiovascular Health Metrics
      Among Employees of a Large Healthcare Organization: The Baptist Health South
      Florida Employee Study.
AB  - BACKGROUND: Healthcare organizations and their employees are critical role models
      for healthy living in their communities. The American Heart Association (AHA)
      2020 impact goal provides a national framework that can be used to track the
      success of employee wellness programs with a focus on improving cardiovascular
      (CV) health. This study aimed to assess the CV health of the employees of Baptist
      Health South Florida (BHSF), a large nonprofit healthcare organization.
      HYPOTHESIS: HRAs and wellness examinations can be used to measure the
      cardiovascular health status of an employee population. METHODS: The AHA's 7 CV
      health metrics (diet, physical activity, smoking, body mass index, blood
      pressure, total cholesterol, and blood glucose) categorized as ideal,
      intermediate, or poor were estimated among employees of BHSF participating
      voluntarily in an annual health risk assessment (HRA) and wellness fair. Age and
      gender differences were analyzed using chi(2) test. RESULTS: The sample consisted
      of 9364 employees who participated in the 2014 annual HRA and wellness fair (mean
      age [standard deviation], 43 [12] years, 74% women). Sixty (1%) individuals met
      the AHA's definition of ideal CV health. Women were more likely than men to meet
      the ideal criteria for more than 5 CV health metrics. The proportion of
      participants meeting the ideal criteria for more than 5 CV health metrics
      decreased with age. CONCLUSIONS: A combination of HRAs and wellness examinations
      can provide useful insights into the cardiovascular health status of an employee
      population. Future tracking of the CV health metrics will provide critical
      feedback on the impact of system wide wellness efforts as well as identifying
      proactive programs to assist in making substantial progress toward the AHA 2020
      Impact Goal.

PMID- 25995162
TI  - Alcohol-Related Road Accidents and Holiday.

PMID- 25995164
TI  - Re: Andy UU, Arya LA, Smith AL, et al. Is self-reported adherence associated with
      clinical outcomes in women treated with anticholinergic medication for overactive
      bladder?. Neurourol Urodyn 2016;35:738-42.

PMID- 25995163
TI  - [Sphincter of Oddi dyskinesia].
AB  - Sphincter of Oddi dyskinesia is a functional disorder of the papillary region
      which can lead to clinical symptoms due to functional obstruction of biliary and
      pancreatic outflow. Based on the severity of the clinical symptoms the disorder
      can be graded into three types (biliary and pancreatic types I-III). The
      manometric diagnosis of this disorder using sphincter of Oddi manometry is
      hampered by the relatively high risk of pancreatitis after endoscopic retrograde
      cholangiopancreatography. Although papillary manometry is often carried out in
      North America, in Europe this is the exception rather than the rule.
      Manometrically, sphincter of Oddi dyskinesia is characterized by an increased
      pressure in the biliary and/or the pancreatic sphincter segments and can be
      treated by endoscopic papillotomy. This overview counterbalances the arguments
      for primary invasive diagnostics and a pragmatic clinical approach, i.e.
      papillotomy should be directly carried out when a sphincter of Oddi dyskinesia is
      clinically suspected. For patients with biliary or pancreatic type I, endoscopic
      papillotomy is the treatment of choice. In biliary type II sphincter of Oddi
      manometry could be helpful for clinical decision-making; however, the exact risk
      benefit ratio is still difficult to assess. In type III patient selection and the
      low predictive value of manometry for treatment success questions the clinical
      usefulness of sphincter of Oddi manometry.

PMID- 25995165
TI  - A Chromosome 13 locus is associated with male-specific mortality in mice.
AB  - BACKGROUND AND AIM: Mortality is a highly complex trait influenced by a wide
      array of genetic factors. METHODS: We examined a population of 1200 mice that
      were F2 generation offspring of a 4-way reciprocal cross between C57BL6/J and
      DBA2/J strains. Animals were sacrificed at age 200, 500, or 800 days and
      genotyped at 96 markers. The 800 days old cohort, which were the survivors of a
      much larger breeding group, were examined for enriched frequency of alleles that
      benefit survival and depletion of alleles that reduce survival. RESULTS: Loci on
      Chr 13 in males and on Chr X in females were significantly distorted from
      Mendelian expectations, even after conservative correction for multiple testing.
      DBA2/J alleles between 35 and 80 Mb on Chr 13 were underrepresented in the age
      800 male animals. D2 genotypes in this region were also associated with premature
      death during behavioral testing. Furthermore, confirmatory analysis showed BXD
      recombinant inbred strains carrying the D2 alleles in this region had shorter
      median survival. Exploration of available pathology data indicated that a
      syndrome involving dental malocclusions, pancreatic islet hypertrophy, and kidney
      lipidosis may have mediated the effects of DBA alleles on mortality specifically
      in male mice. The heterozygote advantage locus on the X Chr was not found to be
      associated with any pathology. CONCLUSIONS: These results suggest a novel locus
      influencing survival in the B6/D2 genetic background, perhaps via a metabolic
      disorder that emerges by 200 days of age in male animals.

PMID- 25995166
TI  - Aging-related decrements during specific phases of the dual-task Timed Up-and-Go
      test.
AB  - BACKGROUND: It is unclear how young and older adults modulate dual-task mobility
      under changing postural challenges. AIM: To examine age-related changes in dual
      task processing during specific phases of dual-task Timed Up-and-Go (TUGdual
      task). METHOD: Healthy young and older adults performed the Timed Up-and-Go (TUG)
      with the following dual-task conditions: (1) serial-three subtractions, (2)
      carrying cup of water, (3) combined subtraction and carrying water, and (4)
      dialing cell phone. The primary outcome was the dual-task cost on performance of
      TUG (percent change from single- to dual-task) based on duration and peak trunk
      velocity of each phase: (a) straight-walk, (b) sit-to-stand, (c) turn, (d) turn
      to-sit. Mixed-design univariate analysis of variance was performed for each type
      of task. RESULTS: Older adults had more pronounced mobility decrements than young
      adults during straight-ahead walking and turns when the secondary task engaged
      both cognitive and manual modalities. Simple cognitive or manual tasks during
      TUGdual-task did not differentiate young from older participants. Subtraction
      performance during simple and complex cognitive conditions differed by phase of
      the TUG. Manual task performance of carrying water did not vary by phase or age.
      DISCUSSION: Our findings suggest that dual-task processing is dynamic across
      phases of TUGdual-task. Aging-related dual-task decrements are demonstrated
      during straight-ahead walking and turning, particularly when the secondary task
      is more complex. CONCLUSION: Older adults are susceptible to reduced dual-task
      mobility during straight-ahead walking and turning particularly when attentional
      loading was increased.

PMID- 25995168
TI  - Plasma concentrations of transthyretin in older Sardinians including
      centenarians.
AB  - BACKGROUND AND AIMS: Plasma concentrations of transthyretin (TTR), a negative
      acute-phase protein, can be influenced by many factors including aging. Under
      physiological circumstances, TTR concentrations are very low in the fetus,
      increase slowly after birth up to the fifth decade and, then, decrease slowly.
      Some studies have shown sex-related differences up to about 70 years, when the
      differences disappear. The aim of this study was to evaluate the change in TTR
      concentrations in healthy males and females aged more than sixty, including
      numerous centenarians living in Sardinia, a large Italian island located in the
      Mediterranean Sea. METHODS: The study sample consisted of 211 healthy subjects
      grouped by age and sex (male/female ratio: 1:1). Plasma TTR was assessed using a
      non-competitive enzyme immunoassay (ELISA Assaypro LLC, prealbumin AssayMAX Human
      ELISA Kit). RESULTS: In subjects aged between 60 and 99 years, plasma TTR
      concentrations were higher compared to the reference ranges reported by CRM 470.
      Moreover, unlike other studies, sex-related differences in TTR concentrations
      were only observed in nonagenarians and centenarians. CONCLUSIONS: We hypothesize
      that there are TTR-related genetic differences between the Sardinian population
      and other Caucasian ethnic groups. Further studies and a larger sample are needed
      to confirm our hypothesis.

PMID- 25995167
TI  - Discrepancies between cognition and decision making in older adults.
AB  - BACKGROUND AND AIMS: There is increasing clinical and legal interest in
      discrepancies between decision-making ability and cognition in old age, a stage
      of life when decisions have major ramifications. We investigated the frequency
      and correlates of such discrepancies in non-demented older adults participating
      in a large community-based cohort study of aging, the Rush Memory and Aging
      Project. METHODS: Participants [n = 689, mean age 81.8 (SD 7.6), mean education
      15.2 (SD 3.1), 76.8 % female and 93.3 % white] completed a measure of financial
      and healthcare decision making (DM) and a battery of 19 neuropsychological tests
      from which a composite measure of global cognition (COG) was derived. RESULTS:
      Results indicated that 23.9 % of the sample showed a significant discrepancy
      between DM and COG abilities. Of these, 12.9 % showed DM < COG, while 11.0 %
      showed DM > COG. Logistic regression models showed older age, being non-white,
      greater temporal discounting, and greater risk aversion were associated with
      higher odds of being in the DM < COG group. Being male was associated with higher
      odds of being in the DM > COG group. Education, income, depressive symptoms, and
      impulsivity were not associated with a discrepancy. Only demographic associations
      (age, sex, and race) remained significant in a fully adjusted model with terms
      included for all factors. CONCLUSION: These results support the consideration of
      decision making and cognition as potentially separate constructs.

PMID- 25995169
TI  - Development of population pharmacokinetics model of icotinib with non-linear
      absorption characters in healthy Chinese volunteers to assess the CYP2C19
      polymorphism and food-intake effect.
AB  - PURPOSE: Icotinib is a potent and selective inhibitor of epidermal growth factor
      receptors (EGFR) approved to treat non-small cell lung cancer (NSCLC). However,
      its high variability may impede its application. The objectives of this analysis
      were to assess plasma pharmacokinetics and identify covariates that may explain
      variability in icotinib absorption and/or disposition following single dose of
      icotinib in healthy volunteers. METHODS: Data from two clinical studies (n = 22)
      were analyzed. One study was designed as three-period and Latin-squared (six
      sequence) trial to evaluate dose proportionality, and the other one was designed
      as two-way crossover trial to evaluate food effect on pharmacokinetics (PK)
      characters. Icotinib concentrations in plasma were analyzed using non-linear
      mixed-effects model (NONMEM) method. The model was used to assess influence of
      food, demographic characteristics, measurements of blood biochemistry, and
      CYP2C19 genotype on PK characters of icotinib in humans. The final model was
      diagnosed by goodness-of-fit plots and evaluated by visual predictive check (VPC)
      and bootstrap methods. RESULTS: A two-compartment model with saturated absorption
      character was developed to capture icotinib pharmacokinetics. Typical value of
      clearance, distribution clearance, central volume of distribution, maximum
      absorption rate were 29.5 L/h, 24.9 L/h, 18.5 L, 122.2 L and 204,245 MUg/h,
      respectively. When icotinib was administrated with food, bioavailability was
      estimated to be increased by 48%. Inter-occasion variability was identified to
      affect on maximum absorption rate constant in food-effect study. CL was
      identified to be significantly influenced by age, albumin concentration (ALB),
      and CYP2C19 genotype. No obvious bias was found by VPC and bootstrap methods.
      CONCLUSIONS: The developed model can capture icotinib pharmacokinetics well in
      healthy volunteers. Food intake can increase icotinib exposure. Three covariates,
      age, albumin concentration, and CYP2C19 genotype, were identified to
      significantly affect icotinib PK profiles in healthy subjects.

PMID- 25995170
TI  - The use of melatonin in Swedish children and adolescents--a register-based study
      according to age, gender, and medication of ADHD.
AB  - PURPOSE: The use of melatonin is increasing among Swedish children and
      adolescents despite deficient knowledge of usage in these groups. The aim of this
      study was to investigate the use of melatonin in Swedish children and adolescents
      according to age, gender, dosage, treatment duration, and use of attention
      deficit hyperactivity disorder (ADHD) medication. METHODS: Data from the Swedish
      Prescribed Drug Register was analyzed for children and adolescents 0-19 years old
      in Sweden during 2006-2013. RESULTS: The number of new users of melatonin in 2013
      was 4296 and 3093 among boys and girls, respectively. Girls started treatment
      with melatonin in older ages compared to boys. Regular users of melatonin were
      most common among boys 10-14 years. The average defined daily dose (DDD) per
      regular user was decreasing from 2.4 DDD in 2006 to 1.7 DDD in 2012. Among girls
      and boys 5-9 years who were regular users in 2010, over 40 and 50%, respectively,
      were still regular users in 2013. In the age group 15-19 years, only about 10%
      were still regular users in 2013. In 2013, 65% of boys and 49% of girls, using
      melatonin regularly, also used medication for ADHD regularly. CONCLUSIONS: More
      Swedish boys than girls used melatonin regularly. The boys started treatment
      earlier and more often combined regular use of melatonin with regular use of
      medication for ADHD. This indicates that girls and boys partly are prescribed
      melatonin for different reasons. About half of the younger children stayed on
      melatonin treatment for several years, while 90% of adolescents (15-19 years)
      concluded their treatment.

PMID- 25995171
TI  - Predictive factors for difficult robotic thyroidectomy using the bilateral axillo
      breast approach.
AB  - BACKGROUND: The purpose of this study was to identify predictors of difficult
      robotic thyroidectomy using the bilateral axillo-breast approach (BABA) for the
      management of patients with papillary thyroid carcinoma (PTC). METHODS: We
      examined a database containing details of patients with PTC who had undergone
      robotic thyroidectomy with cervical lymph node dissection between July 2008 and
      June 2013. Patients were subgrouped into difficult thyroidectomy and non
      difficult thyroidectomy to identify predictors associated with difficult
      thyroidectomy corresponding to the time of operation. Clinicopathologic
      characteristics, surgical outcomes, and postoperative morbidities were
      investigated. RESULTS: Male sex was the only significantly different
      clinicopathologic factor between the 2 groups (p = .013). Other factors, such as
      age (p = .809) and body mass index (BMI; p = .202), were comparable between the 2
      groups. The rates of postoperative complications, such as hypoparathyroidism,
      vocal cord palsy, and seroma, in the difficult thyroidectomy group were not
      significantly different from those in the non-difficult thyroidectomy group.
      There was no hematoma or wound infection. Male sex was the only independent
      factor associated with difficult thyroidectomy (odds ratio [OR] = 5.379; 95%
      confidence interval [CI] = 1.052-27.502; p = .043), according to the multivariate
      logistic regression model. CONCLUSION: Male sex was the only predictive factor
      for difficult robotic thyroidectomy using BABA. Further evaluations should be
      performed to ascertain additional factors associated with difficult robotic
      thyroidectomy. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E954-E960, 2016.

PMID- 25995172
TI  - c-myc in whitefish (Coregonus lavaretus): structure, expression, and insights
      into possible posttranscriptional regulatory mechanism.
AB  - c-myc has a crucial function in growth control, differentiation, and apoptosis of
      vertebrate cells. Despite the important role of c-myc in mediating the biological
      effects, studies of c-myc gene expression and factors that control it in
      organisms other than mammals, such as fish, have been rare. In the current study,
      we asked whether c-myc mRNA of whitefish, a feasible organism for pollution
      monitoring in aquatic systems and a model in toxicological research, contains
      activity sites for regulatory motifs in its 5'- and 3'-UTRs, similar to those
      found in mammals. We were particularly interested in whether miRNA-34, a known
      negative regulator of c-myc's in mammals, is able to regulate c-myc in fish. To
      answer these questions, we determined the mRNA sequence of whitefish c-myc and
      inferred the structure of the protein that it codes for. We found that the active
      sites of mRNA and structures of the inferred c-myc protein are similar to those
      found in mammals and other fish. Remarkably, levels of c-myc mRNA expression were
      very high in ovaries compared to other tissues of whitefish, thus corroborating
      previous data in fish. Using bioinformatic searches on c-myc 3'-UTR, we confirmed
      the presence of two miRNA-34a (miR-34a) response elements. Luciferase reporter
      assay showed that activity of reporters containing either the miR response
      elements or entire c-myc 3'-UTR was significantly reduced (p < 0.001) by ectopic
      expression of miR-34a. Therefore, we further investigated possible involvement of
      miR-34a in c-myc gene silencing by profiling the expression of both genes in
      livers of whitefish treated for 8, 24, 48 h with MC-LR, a potent c-myc inducer in
      mammals. Although the difference was only significant at p = 0.08, the expression
      of c-myc mRNA in challenged whitefish after 24 h of the treatment was notably
      higher than that in livers of control fish. Concurrently, we noticed slight but
      significant up-regulation of miR-34a after 24 and 48 h of the challenge (p <
      0.05); however, we found no significant correlation of the c-myc mRNA levels and
      miR-34a expression. Together, these results suggest that miR-34a might regulate c
      myc gene expression in whitefish liver; however, their involvement in MC-LR
      hepatotoxicity should be clarified in future studies. 

PMID- 25995173
TI  - On Patient Safety: "Is There a Gun in the Home?".

PMID- 25995174
TI  - Low Albumin Levels, More Than Morbid Obesity, Are Associated With Complications
      After TKA.
AB  - BACKGROUND: Morbid obesity and malnutrition are thought to be associated with
      more frequent perioperative complications after TKA. However, morbid obesity and
      malnutrition often are co-occurring conditions. Therefore it is important to
      understand whether morbid obesity, malnutrition, or both are independently
      associated with more frequent perioperative complications. In addition, assessing
      the magnitude of an increase in complications and whether these complications are
      major or minor is important for both conditions. QUESTIONS/PURPOSES: We asked:
      (1) Is morbid obesity independently associated with more frequent major
      perioperative complications after TKA? (2) Are major perioperative complications
      after TKA more prevalent among patients with a low serum albumin? METHODS: The
      National Surgical Quality Improvement Program (NSQIP) database was analyzed from
      2006 to 2013. Patients were grouped as morbidly obese (BMI >= 40 kg/m(2)) or
      nonmorbidly obese (BMI >= 18.5 kg/m(2) to < 40 kg/m(2)), or by low serum albumin
      (serum albumin level < 3.5 mg/dL) or normal serum albumin (serum albumin level >=
      3.5 mg/dL). The study cohort included 77,785 patients, including 35,573 patients
      with a serum albumin level of 3.5 g/dL or greater and 1570 patients with a serum
      albumin level less than 3.5 g/dL. Therefore, serum albumin levels were available
      for only 37,173 of the 77,785 of the patients (48%). There were 66,382 patients
      with a BMI between 18.5 kg/m(2) and 40 kg/m(2) and 11,403 patients with a BMI
      greater than 40 kg/m(2). Data were recorded on patient mortality along with 21
      complications reported in the NSQIP. We also developed three composite
      complication variables to represent risk of any infections, cardiac or pulmonary
      complications, and any major complications. For each complication, multivariate
      logistic regression analysis was performed. Independent variables included
      patient age, sex, race, BMI, American Society of Anesthesiologists
      classification, year of surgery, and Charlson comorbidity index score. RESULTS:
      Mortality was not increased in the morbidly obese group (0.14% vs 0.14%; p =
      0.942). Patients who were morbidly obese were more likely to have progressive
      renal insufficiency (0.30% vs 0.10%; odds ratio [OR], 2.47; 95% CI, 1.27-4.29; p
      < 0.001), superficial infection (1.07% vs 0.55%; OR, 1.87; 95% CI, 1.39-2.51; p <
      0.001), and sepsis (0.36% vs 0.23%; OR, 1.70; 95% CI, 1.04-2.53; p = 0.034)
      compared with patients who were not morbidly obese. Patients who were morbidly
      obese were less likely to require blood transfusion (8.68% vs 12.06%; OR, 0.70;
      95% CI, 0.63-0.77; p < 0.001) compared with patients who were not morbidly obese.
      Morbid obesity was not associated with any of the other 21 perioperative
      complications recorded in the NSQIP database. With respect to the composite
      complication variables, patients who were morbidly obese had an increased risk of
      any infection (3.31% vs 2.41%; OR, 1.38; 95% CI, 1.16-1.64; p < 0.001) but not
      for cardiopulmonary or any major complication. The group with low serum albumin
      had higher mortality than the group with normal serum albumin (0.64% vs 0.15%;
      OR, 3.17; 95% CI, 1.58-6.35; p = 0.001). Patients in the low serum albumin group
      were more likely to have a superficial surgical site infection (1.27% vs 0.64%;
      OR, 1.27; 95% CI, 1.09-2.75; p = 0.020); deep surgical site infection (0.38% vs
      0.12%; OR, 3.64; 95% CI, 1.54-8.63; p = 0.003); organ space surgical site
      infection (0.45% vs 0.15%; OR, 2.71; 95% CI, 1.23-5.97; p = 0.013); pneumonia
      (1.21 vs 0.29%; OR, 3.55; 95% CI, 2.14-5.89; p < 0.001); require unplanned
      intubation (0.51% vs 0.17%, OR, 2.24; 95% CI, 1.07-4.69; p = 0.033); and remain
      on a ventilator more than 48 hours (0.38% vs 0.07%; OR, 4.03; 95% CI, 1.64-9.90;
      p = 0.002). They are more likely to have progressive renal insufficiency (0.45 %
      vs 0.12%; OR, 2.71; 95% CI, 1.21-6.07; p = 0.015); acute renal failure (0.32% vs
      0.06%; OR, 5.19; 95% CI, 1.96-13.73; p = 0.001); cardiac arrest requiring
      cardiopulmonary resuscitation (0.19 % vs 0.12%; OR, 3.74; 95% CI, 1.50-9.28; p =
      0.005); and septic shock (0.38% vs 0.08%; OR, 4.4; 95% CI, 1.74-11.09; p =
      0.002). Patients in the low serum albumin group also were more likely to require
      blood transfusion (17.8% vs 12.4%; OR, 1.56; 95% CI, 1.35-1.81; p < 0.001). In
      addition, among the three composite complication variables, any infection (5.0%
      vs 2.4%; OR, 2.0; 95% CI, 1.53-2.61; p < 0.001) and any major complication (2.4%
      vs 1.3%; OR, 1.41; 95% CI, 1.00-1.97; p = 0.050) were more prevalent among the
      patients with low serum albumin. There was no difference for cardiopulmonary
      complications. CONCLUSIONS: Morbid obesity is not independently associated with
      the majority of perioperative complications measured by the NSQIP and was
      associated only with increases in progressive renal insufficiency, superficial
      surgical site infection, and sepsis among the 21 perioperative variables
      measured. However, low serum albumin was associated with increased mortality and
      multiple additional major perioperative complications after TKA. Low serum
      albumin, more so than morbid obesity, is associated with major perioperative
      complications. This is an important finding, as low serum albumin may be more
      modifiable than morbid obesity in patients who are immobile or have advanced knee
      osteoarthritis. LEVEL OF EVIDENCE: Level III, prognostic study.

PMID- 25995175
TI  - Clinical Faceoff: Controversies in the Management of Distal Radius Fractures.

PMID- 25995177
TI  - CORR Insights ((r)): Are There Modifiable Risk Factors for Hospital Readmission
      After Total Hip Arthroplasty in a US Healthcare System?

PMID- 25995176
TI  - What Are the Prognostic Factors for Radiographic Progression of Knee
      Osteoarthritis? A Meta-analysis.
AB  - BACKGROUND: A previous systematic review on prognostic factors for knee
      osteoarthritis (OA) progression showed associations for generalized OA and
      hyaluronic acid levels. Knee pain, radiographic severity, sex, quadriceps
      strength, knee injury, and regular sport activities were not associated. It has
      been a decade since the literature search of that review and many studies have
      been performed since then investigating prognostic factors for radiographic knee
      OA progression. QUESTIONS/PURPOSES: The purpose of this study is to provide an
      updated systematic review of available evidence regarding prognostic factors for
      radiographic knee OA progression. METHODS: We searched for observational studies
      in MEDLINE and EMBASE. Key words were: knee, osteoarthritis (or arthritis, or
      arthrosis, or degenerative joint disease), progression (or prognosis, or
      precipitate, or predictive), and case-control (or cohort, or longitudinal, or
      follow-up). Studies fulfilling the inclusion criteria were assessed for
      methodologic quality according to established criteria for reviews on prognostic
      factors in musculoskeletal disorders. Data were extracted and results were pooled
      if possible or summarized according to a best-evidence synthesis. A total of 1912
      additional articles were identified; 43 met our inclusion criteria. The previous
      review contained 36 articles, thus providing a new total of 79 articles. Seventy
      two of the included articles were scored high quality, the remaining seven were
      low quality. RESULTS: The pooled odds ratio (OR) of two determinants showed
      associations with knee OA progression: baseline knee pain (OR, 2.38 [95% CI, 1.74
      3.27) and Heberden nodes (OR, 2.66 [95% CI, 1.46-8.84]). Our best-evidence
      synthesis showed strong evidence that varus alignment, serum hyaluronic acid, and
      tumor necrosis factor-alpha are associated with knee OA progression. There is
      strong evidence that sex, former knee injury, quadriceps strength, smoking,
      running, and regular performance of sports are not associated with knee OA
      progression. Evidence for the majority of determined associations, however, was
      limited, conflicting, or inconclusive. CONCLUSIONS: Baseline knee pain, presence
      of Heberden nodes, varus alignment, and high levels of serum markers hyaluronic
      acid and tumor necrosis factor-alpha predict knee OA progression. Sex, knee
      injury, and quadriceps strength, among others, did not predict knee OA
      progression. Large variation remains in definitions of knee OA and knee OA
      progression. Clinical studies should use more consistent definitions of these
      factors to facilitate data pooling by future meta-analyses.

PMID- 25995178
TI  - Surgical hip dislocation is a reliable approach for treatment of femoral head
      fractures.
AB  - BACKGROUND: Femoral head fractures are rare injuries; incongruency and
      instability are indications for surgical intervention. Anterior, posterior, and
      transtrochanteric surgical approaches have been proposed, but the exposure is
      limited with classical approaches. Surgical hip dislocation allows for a 360
      degrees  view of the head and may facilitate a reduction in selected head
      fractures, but to our knowledge, few studies have reported on the results with
      this technique. We therefore report on the (1) quality of fracture reduction; (2)
      modified Harris hip score at a minimum of 2 years (mean, 6 years, range, 26-122
      months); and (3) frequency of complications, including avascular necrosis (AVN),
      arthritis development, and heterotopic ossification, in a case series of patients
      with femoral head fractures treated with this approach. DESCRIPTION OF TECHNIQUE:
      The procedure involves digastric trochanteric flip osteotomy and safe dislocation
      of the femoral head, preserving its vessels. Using this technique we are able to
      reduce all displaced femoral head fractures under direct view. Definitive
      fixation is performed through this approach with 2.7-mm nonabsorbable screws. The
      same technique may be used also for Pipkin IV fractures to fix transverse, T
      type, posterior wall, or posterior column acetabular fracture. METHODS: Between
      2004 and 2011, we used this approach to manage all displaced femoral head
      fractures in patients younger than 55 years old. A total of 17 patients were thus
      treated; of those three were lost to followup before 2 years, and one was
      excluded from study because of severe preoperative neurological impairment,
      leaving 13 for analysis here. Patient demographic, injury, and surgical variables
      as well as complications were recorded and retrospectively evaluated.
      Radiographic outcome was scored according to Matta's criteria on postoperative
      radiographs. Outcomes were evaluated with the modified Harris hip score. Minimum
      followup was 24 months (mean, 77 months; SD, 32.8 months). RESULTS: Fracture
      reduction was anatomic in eight hips and imperfect in five. Mean clinical score
      was 82 points (SD, 7.7). One patient developed symptomatic femoral head AVN and
      underwent total hip arthroplasty 4 years after the index procedure; no other
      patient underwent arthroplasty. Besides this patient, signs of arthritis (Grade I
      according to Tonnis classification) were found in one patient and heterotopic
      ossification was recorded in two patients, but neither was symptomatic.
      CONCLUSIONS: Our experience with surgical dislocation shows clinical results
      comparable to previously reported outcomes in femoral head fractures treated with
      common approaches; we also present a similar rate of AVN and a lower rate of
      posttraumatic arthritis, but a higher risk of heterotopic ossification. Further
      case-control studies are necessary to confirm these statements. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 25995179
TI  - Are Complications Associated With the Repiphysis((r)) Expandable Distal Femoral
      Prosthesis Acceptable for Its Continued Use?
AB  - BACKGROUND: Reconstruction of the distal femur after resection for malignant bone
      tumors in skeletally immature children is challenging. The use of megaprostheses
      has become increasingly popular in this patient group since the introduction of
      custom-made, expandable devices that do not require surgery for lengthening, such
      as the Repiphysis((r)) Limb Salvage System. Early reports on the device were
      positive but more recently, a high complication rate and associated bone loss
      have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical
      outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5
      year minimum followup in patients treated with this prosthesis at one center; (2)
      what are the problems and complications associated with the lengthening
      procedures of this implant; and (3) what are the specific concerns associated
      with revision of this implant? METHODS: At our institute, between 2002 and 2007,
      the Repiphysis((r)) expandable prosthesis was implanted in 15 children (mean age,
      8 years; range, 6-11 years) after distal femoral resection for malignant bone
      tumors. During this time, the general indication for use of this implant was
      resection of the distal femur for localized malignant bone tumors in pediatric
      patients. Alternative techniques used for this indication were modular prosthetic
      reconstruction, massive (osteoarticular or intercalary) allograft reconstruction,
      or rotationplasty. Age and tumor extension were the main factors to decide on the
      surgical indication. Of the 15 patients who had this prosthesis implanted during
      reconstruction surgery, five died with the implant in situ or underwent
      amputation before 5 years followup and the remaining 10 were evaluated at a
      minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were
      lost to followup. These 10 patients were long-term survivors and underwent the
      lengthening program. They were included in our study analysis. The first seven
      lengthening procedures were attempted in an outpatient setting; however, owing to
      pain and burning sensations experienced by the patients, the procedures failed to
      achieve the desired lengthening. Therefore, other procedures were performed with
      the patients under general anesthesia. We reviewed clinical data at index surgery
      for all 15 patients. We further analyzed the lengthening procedures, implant
      survival, radiographic and functional results, for the 10 long-term survivors.
      Functional results were assessed according to the MSTS scoring system.
      Complications were classified according to the International Society of Limb
      Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors
      underwent revision of the implant for mechanical failure. They had a mean MSTS
      score of 64% (range, 47%-87%) before revision surgery. At final followup the 10
      long-term surviving patients had an average MSTS score of 81% (range, 53%-97%).
      In total, we obtained an average lengthening of 39 mm per patient (range, 17-67
      mm). Exact expansion of the implant was unpredictable and difficult to control.
      Nine of 10 of the long-term surviving patients underwent revision surgery of the
      prosthesis-eight for implant breakage and one for stem loosening. At revision
      surgery, six patients had another type of expandable prosthesis implanted and
      three had an adult-type megaprosthesis implanted. In five cases, segmental bone
      grafts were used during revision surgery to compensate for loss of bone stock.
      CONCLUSIONS: We could not comfortably expand the Repiphysis((r)) prosthesis in an
      outpatient setting because of pain experienced by the patients during the
      lengthening procedures. Furthermore, use of the prosthesis was associated with
      frequent failures related to implant breakage and stem loosening. Revisions of
      these procedures were complex and difficult. We no longer use this prosthesis and
      caution others against the use of this particular prosthesis design. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 25995180
TI  - Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis
      patients and its impact on peritonitis.
AB  - BACKGROUND: Peritoneal dialysis (PD) exchange procedure is complex. Patients with
      cognitive impairment (CI) may require assistance. We studied the prevalence of CI
      among PD patients, its impact on PD-related peritonitis and the outcome of
      assisted PD. METHODS: Cantonese version of Mini-Mental State examination (CMMSE)
      was performed in 151 patients newly started on PD. Data on patient
      characteristics including demographics, co-morbidities, blood parameters,
      medications, and number of PD-related peritonitis in the first 6 months were
      collected. RESULTS: 151 subjects were recruited. The age of studied patients was
      60 +/- 15.0 years, and 45% were female. The prevalence of CI was 13.9% using
      education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and
      lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR
      14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year
      old is an independent risk factor for PD-related peritonitis but CI was not.
      Patients requiring assisted PD were of older age (p < 0.001), lower CMMSE (p <
      0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p <
      0.001). Compared with self-care PD patients, assisted PD patients did not have
      higher rates exit site infection (p = 0.30) but had a trend of higher PD
      peritonitis (p = 0.07). CONCLUSION: CI is common among local PD patients.
      Overall, CI could not be identified as an independent risk factor for PD
      peritonitis. There is a higher prevalence of CI among assisted PD patients but
      helpers may not completely eliminate the risk of PD-related peritonitis.

PMID- 25995181
TI  - An alternative method to examine the predictive value of mechanical dyssynchrony.

PMID- 25995182
TI  - Myocardial blood flow quantification by Rb-82 cardiac PET/CT: A detailed
      reproducibility study between two semi-automatic analysis programs.
AB  - BACKGROUND: Several analysis software packages for myocardial blood flow (MBF)
      quantification from cardiac PET studies exist, but they have not been compared
      using concordance analysis, which can characterize precision and bias separately.
      Reproducible measurements are needed for quantification to fully develop its
      clinical potential. METHODS: Fifty-one patients underwent dynamic Rb-82 PET at
      rest and during adenosine stress. Data were processed with PMOD and FlowQuant
      (Lortie model). MBF and myocardial flow reserve (MFR) polar maps were quantified
      and analyzed using a 17-segment model. Comparisons used Pearson's correlation rho
      (measuring precision), Bland and Altman limit-of-agreement and Lin's concordance
      correlation rhoc = rho.C b (C b measuring systematic bias). RESULTS: Lin's
      concordance and Pearson's correlation values were very similar, suggesting no
      systematic bias between software packages with an excellent precision rho for MBF
      (rho = 0.97, rhoc = 0.96, C b = 0.99) and good precision for MFR (rho = 0.83,
      rhoc = 0.76, C b = 0.92). On a per-segment basis, no mean bias was observed on
      Bland-Altman plots, although PMOD provided slightly higher values than FlowQuant
      at higher MBF and MFR values (P < .0001). CONCLUSIONS: Concordance between
      software packages was excellent for MBF and MFR, despite higher values by PMOD at
      higher MBF values. Both software packages can be used interchangeably for
      quantification in daily practice of Rb-82 cardiac PET.

PMID- 25995183
TI  - High-risk coronary artery disease, but normal myocardial perfusion: A matter of
      concern?

PMID- 25995184
TI  - Methods for evaluating the agreement between diagnostic tests.

PMID- 25995185
TI  - The prognostic value of regadenoson stress: Has the case been made?

PMID- 25995187
TI  - Hypoxia drives transient site-specific copy gain and drug-resistant gene
      expression.
AB  - Copy number heterogeneity is a prominent feature within tumors. The molecular
      basis for this heterogeneity remains poorly characterized. Here, we demonstrate
      that hypoxia induces transient site-specific copy gains (TSSGs) in primary,
      nontransformed, and transformed human cells. Hypoxia-driven copy gains are not
      dependent on HIF1alpha or HIF2alpha; however, they are dependent on the KDM4A
      histone demethylase and are blocked by inhibition of KDM4A with a small molecule
      or the natural metabolite succinate. Furthermore, this response is conserved at a
      syntenic region in zebrafish cells. Regions with site-specific copy gain are also
      enriched for amplifications in hypoxic primary tumors. These tumors exhibited
      amplification and overexpression of the drug resistance gene CKS1B, which we
      recapitulated in hypoxic breast cancer cells. Our results demonstrate that
      hypoxia provides a biological stimulus to create transient site-specific copy
      alterations that could result in heterogeneity within tumors and cell
      populations. These findings have major implications in our understanding of copy
      number heterogeneity and the emergence of drug resistance genes in cancer. 

PMID- 25995186
TI  - The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
AB  - Two Parkinson's disease (PD)-associated proteins, the mitochondrial kinase PINK1
      and the E3-ubiquitin (Ub) ligase PARKIN, are central to mitochondrial quality
      control. In this pathway, PINK1 accumulates on defective mitochondria, eliciting
      the translocation of PARKIN from the cytosol to mediate the clearance of damaged
      mitochondria via autophagy (mitophagy). Throughout the different stages of
      mitophagy, post-translational modifications (PTMs) are critical for the
      regulation of PINK1 and PARKIN activity and function. Indeed, activation and
      recruitment of PARKIN onto damaged mitochondria involves PINK1-mediated
      phosphorylation of both PARKIN and Ub. Through a stepwise cascade, PARKIN is
      converted from an autoinhibited enzyme into an active phospho-Ub-dependent E3
      ligase. Upon activation, PARKIN ubiquitinates itself in concert with many
      different mitochondrial substrates. The Ub conjugates attached to these
      substrates can in turn be phosphorylated by PINK1, which triggers further cycles
      of PARKIN recruitment and activation. This feed-forward amplification loop
      regulates both PARKIN activity and mitophagy. However, the precise steps and
      sequence of PTMs in this cascade are only now being uncovered. For instance, the
      Ub conjugates assembled by PARKIN consist predominantly of noncanonical K6-linked
      Ub chains. Moreover, these modifications are reversible and can be disassembled
      by deubiquitinating enzymes (DUBs), including Ub-specific protease 8 (USP8),
      USP15, and USP30. However, PINK1-mediated phosphorylation of Ub can impede the
      activity of these DUBs, adding a new layer of complexity to the regulation of
      PARKIN-mediated mitophagy by PTMs. It is therefore evident that further insight
      into how PTMs regulate the PINK1-PARKIN pathway will be critical for our
      understanding of mitochondrial quality control. 

PMID- 25995188
TI  - piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis.
AB  - MIWI catalytic activity is required for spermatogenesis, indicating that piRNA
      guided cleavage is critical for germ cell development. To identify meiotic piRNA
      targets, we augmented the mouse piRNA repertoire by introducing a human meiotic
      piRNA cluster. This triggered a spermatogenesis defect by inappropriately
      targeting the piRNA machinery to mouse mRNAs essential for germ cell development.
      Analysis of such de novo targets revealed a signature for pachytene piRNA target
      recognition. This enabled identification of both transposable elements and
      meiotically expressed protein-coding genes as targets of native piRNAs. Cleavage
      of genic targets began at the pachytene stage and resulted in progressive
      repression through meiosis, driven at least in part via the ping-pong cycle. Our
      data support the idea that meiotic piRNA populations must be strongly selected to
      enable successful spermatogenesis, both driving the response away from essential
      genes and directing the pathway toward mRNA targets that are regulated by small
      RNAs in meiotic cells. 

PMID- 25995189
TI  - Position-specific binding of FUS to nascent RNA regulates mRNA length.
AB  - More than half of all human genes produce prematurely terminated polyadenylated
      short mRNAs. However, the underlying mechanisms remain largely elusive. CLIP-seq
      (cross-linking immunoprecipitation [CLIP] combined with deep sequencing) of FUS
      (fused in sarcoma) in neuronal cells showed that FUS is frequently clustered
      around an alternative polyadenylation (APA) site of nascent RNA. ChIP-seq
      (chromatin immunoprecipitation [ChIP] combined with deep sequencing) of RNA
      polymerase II (RNAP II) demonstrated that FUS stalls RNAP II and prematurely
      terminates transcription. When an APA site is located upstream of an FUS cluster,
      FUS enhances polyadenylation by recruiting CPSF160 and up-regulates the
      alternative short transcript. In contrast, when an APA site is located downstream
      from an FUS cluster, polyadenylation is not activated, and the RNAP II
      suppressing effect of FUS leads to down-regulation of the alternative short
      transcript. CAGE-seq (cap analysis of gene expression [CAGE] combined with deep
      sequencing) and PolyA-seq (a strand-specific and quantitative method for high
      throughput sequencing of 3' ends of polyadenylated transcripts) revealed that
      position-specific regulation of mRNA lengths by FUS is operational in two-thirds
      of transcripts in neuronal cells, with enrichment in genes involved in synaptic
      activities. 

PMID- 25995190
TI  - Cellular projections from sensory hair cells form polarity-specific scaffolds
      during synaptogenesis.
AB  - The assembly of a nervous system requires the extension of axons and dendrites to
      specific regions where they are matched with appropriate synaptic targets.
      Although the cues that guide long-range outgrowth have been characterized
      extensively, additional mechanisms are required to explain short-range guidance
      in neural development. Using a complementary combination of time-lapse imaging by
      fluorescence confocal microscopy and serial block-face electron microscopy, we
      identified a novel type of presynaptic projection that participates in the
      assembly of the vertebrate nervous system. Synapse formation by each hair cell of
      the zebrafish's lateral line occurs during a particular interval after the cell's
      birth. During the same period, projections emerge from the cellular soma,
      extending toward a specific subpopulation of mature hair cells and interacting
      with polarity-specific afferent nerve terminals. The terminals then extend along
      the projections to reach appropriately matched presynaptic sites, after which the
      projections recede. Our results suggest that presynaptic projections act as
      transient scaffolds for short-range partner matching, a mechanism that may occur
      elsewhere in the nervous system. 

PMID- 25995191
TI  - Brooke-Spiegler syndrome presenting multiple concurrent cutaneous and parotid
      gland neoplasms: cytologic findings on fine-needle sample and description of a
      novel mutation of the CYLD gene.
AB  - Multiple dermal cylindromas and membranous basal cell adenoma of parotid gland in
      a 67-year-old woman with Brooke-Spiegler syndrome (BSS) were examined by fine
      needle cytology. Histology, immunochemistry, and CYLD germline mutation testing
      were also performed. Cytomorphology and immunochemistry of the two lesions showed
      basaloid neoplasms, remarkably similar, composed by proliferating epithelial
      cells of basal type accompanied by a smaller proportion of myoepithelial cells.
      CYLD gene showed a novel germline splice acceptor site mutation (c.2042-1G>C)
      with skipping of the entire exon 15. The occurrence of analogous tumors, dermal
      cylindromas, and membranous basal cell adenoma of the parotid gland, in the same
      patient may result from the action of a single gene on ontogenetically similar
      stem cells. Therefore, patients with BSS should be offered a genetic counselling
      for an early and correct diagnosis.

PMID- 25995192
TI  - The acceptability among health researchers and clinicians of social media to
      translate research evidence to clinical practice: mixed-methods survey and
      interview study.
AB  - BACKGROUND: Establishing and promoting connections between health researchers and
      health professional clinicians may help translate research evidence to clinical
      practice. Social media may have the capacity to enhance these connections.
      OBJECTIVE: The aim of this study was to explore health researchers' and
      clinicians' current use of social media and their beliefs and attitudes towards
      the use of social media for communicating research evidence. METHODS: This study
      used a mixed-methods approach to obtain qualitative and quantitative data.
      Participation was open to health researchers and clinicians. Data regarding
      demographic details, current use of social media, and beliefs and attitudes
      towards the use of social media for professional purposes were obtained through
      an anonymous Web-based survey. The survey was distributed via email to research
      centers, educational and clinical institutions, and health professional
      associations in Australia, India, and Malaysia. Consenting participants were
      stratified by country and role and selected at random for semistructured
      telephone interviews to explore themes arising from the survey. RESULTS: A total
      of 856 participants completed the questionnaire with 125 participants declining
      to participate, resulting in a response rate of 87.3%. 69 interviews were
      conducted with participants from Australia, India, and Malaysia. Social media was
      used for recreation by 89.2% (749/840) of participants and for professional
      purposes by 80.0% (682/852) of participants. Significant associations were found
      between frequency of professional social media use and age, gender, country of
      residence, and graduate status. Over a quarter (26.9%, 229/852) of participants
      used social media for obtaining research evidence, and 15.0% (128/852) of
      participants used social media for disseminating research evidence. Most
      participants (95.9%, 810/845) felt there was a role for social media in
      disseminating or obtaining research evidence. Over half of the participants
      (449/842, 53.3%) felt they had a need for training in the use of social media for
      professional development. A key barrier to the professional use of social media
      was concerns regarding trustworthiness of information. CONCLUSIONS: A large
      majority of health researchers and clinicians use social media in recreational
      and professional contexts. Social media is less frequently used for communication
      of research evidence. Training in the use of social media for professional
      development and methods to improve the trustworthiness of information obtained
      via social media may enhance the utility of social media for communicating
      research evidence. Future studies should investigate the efficacy of social media
      in translating research evidence to clinical practice.

PMID- 25995193
TI  - Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of
      Adults With Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Immunoglobulin (Ig)A proteases of Haemophilus influenzae are highly
      specific endopeptidases that cleave the hinge region of human IgA1 and also
      mediate invasion and trafficking in human respiratory epithelial cells,
      facilitating persistence of H. influenzae. Little is known about the expression
      of IgA proteases in clinical settings of H. influenzae infection. METHODS: We
      identified and characterized IgA protease genes in H. influenzae and studied
      their expression and proteolytic specificity, in vitro and in vivo in 169
      independent strains of H. influenzae collected longitudinally over 10 years from
      adults with chronic obstructive pulmonary disease. RESULTS: The H. influenzae
      pangenome has 2 alleles of IgA protease genes; all strains have igaA, and 40% of
      strains have igaB. Each allele has 2 variants with differing proteolytic
      specificities for human IgA1. A total of 88% of 169 strains express IgA protease
      activity. Expression of the 4 forms of IgA protease varies among strains. Based
      on the presence of IgA1 fragments in sputum samples, each of the different forms
      of IgA protease is selectively expressed in the human airways during infection.
      CONCLUSIONS: Four variants of IgA proteases are variably expressed by H.
      influenzae during infection of the human airways.

PMID- 25995194
TI  - Tracing Origins of the Salmonella Bareilly Strain Causing a Food-borne Outbreak
      in the United States.
AB  - BACKGROUND: Using a novel combination of whole-genome sequencing (WGS) analysis
      and geographic metadata, we traced the origins of Salmonella Bareilly isolates
      collected in 2012 during a widespread food-borne outbreak in the United States
      associated with scraped tuna imported from India. METHODS: Using next-generation
      sequencing, we sequenced the complete genome of 100 Salmonella Bareilly isolates
      obtained from patients who consumed contaminated product, from natural sources,
      and from unrelated historically and geographically disparate foods. Pathogen
      genomes were linked to geography by projecting the phylogeny on a virtual globe
      and produced a transmission network. RESULTS: Phylogenetic analysis of WGS data
      revealed a common origin for outbreak strains, indicating that patients in
      Maryland and New York were infected from sources originating at a facility in
      India. CONCLUSIONS: These data represent the first report fully integrating WGS
      analysis with geographic mapping and a novel use of transmission networks.
      Results showed that WGS vastly improves our ability to delimit the scope and
      source of bacterial food-borne contamination events. Furthermore, these findings
      reinforce the extraordinary utility that WGS brings to global outbreak
      investigation as a greatly enhanced approach to protecting the human food supply
      chain as well as public health in general.

PMID- 25995195
TI  - Whole-Genome Sequencing: Opportunities and Challenges for Public Health, Food
      borne Outbreak Investigations, and the Global Food Supply.

PMID- 25995197
TI  - Preservation of T-Helper Type 17 Cells in Idiopathic CD4+ Lymphopenia: A New
      Perspective Relevant to HIV Infection?

PMID- 25995196
TI  - Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After
      Immediate Antiretroviral Therapy in Acute HIV Infection.
AB  - BACKGROUND: It is unknown whether neuronal injury begins during acute human
      immunodeficiency virus (HIV) infection, and whether immediate initiation of
      combination antiretroviral therapy (cART) prevents neuronal injury. METHODS:
      Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal
      injury, was assessed before and after cART initiation in individuals starting
      treatment during acute or chronic HIV infection. Nonparametric statistics
      examined relationships between NFL and disease progression, neuroinflammation,
      and cognitive performance. RESULTS: Before treatment, subjects with acute
      infection had lower CSF NFL levels, with elevations for their age in 1 of 32
      subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P
      = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9
      chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection,
      pre-cART NFL levels were inversely correlated with proton magnetic resonance
      spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = 
      0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray
      matter (r = -0.47; P = .01); correlations persisted after treatment in the
      frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P
      = .04). CONCLUSIONS: CSF NFL levels are not elevated in untreated acute HIV
      infection or after 6 months of immediately initiated cART but are abnormal in
      chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL
      levels are inversely associated with neuroimaging markers of neuronal health.

PMID- 25995199
TI  - How members of the public interpret the word accident.

PMID- 25995198
TI  - T-Cell Depletion in the Colonic Mucosa of Patients With Idiopathic CD4+
      Lymphopenia.
AB  - Idiopathic CD4(+) lymphopenia (ICL) is a rare syndrome characterized by low
      peripheral CD4(+) T-cell counts that can lead to serious opportunistic
      infections. The pathogenesis of ICL remains unclear, and whether effector sites
      are also lymphopenic is unknown. In this study, rectosigmoid mucosal biopsy
      specimens from patients with ICL and healthy controls were evaluated. Significant
      T-cell lymphopenia was observed in the mucosal tissue of patients with ICL by
      flow cytometry and immunohistochemistry, compared with healthy controls.
      Functional capacity of T cells, assessed by production of interferon gamma and
      interleukin 17, was preserved in the mucosa of patients with ICL. In contrast to
      T lymphocytes, the frequency of myeloid cells (neutrophils and macrophages) was
      elevated in the colonic mucosa of patients with ICL. Despite the observed mucosal
      abnormalities, plasma levels of intestinal fatty acid binding protein, a marker
      of enterocyte turnover and other inflammatory biomarkers, including interleukin
      6, C-reactive protein, and tumor necrosis factor, were not elevated in patients
      with ICL, compared with healthy controls, whereas soluble CD14 levels were
      minimally elevated. These data suggest that patients with ICL, despite gut
      mucosal lymphopenia and local tissue inflammation, have preserved enterocyte
      turnover and T-helper type 17 cells with minimal systemic inflammation. These
      observations highlight differences from patients with human immunodeficiency
      virus infection, with or without AIDS, and may partially explain their distinct
      clinical prognosis. 

PMID- 25995200
TI  - Will the final battle not be between good and evil, but rather injuriologists and
      accidentologists?

PMID- 25995201
TI  - Global status report on violence prevention 2014.

PMID- 25995202
TI  - Capitalising on research-industry partnerships to advance injury prevention.

PMID- 25995203
TI  - The Illness Beliefs Model: advancing practice knowledge about illness beliefs,
      family healing, and family interventions.

PMID- 25995204
TI  - Exploring the beliefs of Japanese mothers caring for a child with disabilities.
AB  - The purpose of this study was to describe the beliefs of Japanese mothers caring
      for a child with disabilities to advance knowledge about beliefs of Japanese
      families experiencing illness. A semistructured interview was conducted with
      eight mothers who had a child with disabilities (physical, intellectual, and/or
      developmental). The interview invited their reflections about "mutual thoughts of
      family members" and family relationships in the context of daily life of caring
      for a child with disabilities. Data were qualitatively analyzed inductively and
      deductively and compared with the Common Tentative Framework of Japanese Family
      Beliefs developed from previous research. The analyses highlighted new
      understandings of the influence of Japanese cultural and societal beliefs on the
      family's experience of having a child with disabilities. Clinical implications
      are discussed and directions for future research suggested. 

PMID- 25995205
TI  - Nck adaptor proteins modulate differentiation and effector function of T cells.
AB  - Understanding the molecular mechanisms regulating T cell reactivity is required
      for successful reprogramming of immune responses in medical conditions,
      characterized by dysfunctions of the immune system. Nck proteins are cytoplasmic
      adaptors mediating diverse cellular functions, including TCR signaling. By
      enhancing TCR signal strength, Nck proteins influence thymic selection and
      regulate the size and sensitivity of the peripheral T cell repertoire. Here, we
      investigated the contribution of Nck proteins to CD4(+) T cell differentiation
      and effector function using Nck.T(-/-) mice. Impaired GC formation and reduced
      Tfh were observed in Nck.T(-/-) mice after immunization with T cell-dependent
      antigens. Th2/Tfh-related cytokines, such as IL-4, IL-10, and IL-21, were
      decreased in Nck.T(-/-) mice T cells. Moreover, an increased susceptibility to
      cell death of Tfh cells in Nck.T(-/-) mice was associated with decreased levels
      of Akt phosphorylation. As a result of this dysregulation in Tfh cells of Nck.T(
      /-) mice, we found impaired production and affinity maturation of antibodies
      against T cell-dependent antigens. Thus, Nck proteins not only participate in
      thymic selection and generation of the peripheral T cell repertoire but also are
      involved in the differentiation and effector functions of CD4(+) T cells. 

PMID- 25995207
TI  - Clinical Features of Patients With Ebola Virus Disease in Sierra Leone.
AB  - BACKGROUND: Clinical and laboratory data available on patients with Ebola virus
      disease (EVD) remain extremely limited. We summarized the clinical
      characteristics of patients with EVD and analyzed the factors related to their
      death. METHODS: Patients admitted for care at the Freetown China-Sierra Leone
      Friendship Hospital during 1 October-14 November 2014 were enrolled in this
      study. The clinical data of these patients were retrospectively analyzed.
      RESULTS: Sixty-one patients were confirmed to have EVD; 28 of them (45.9%) were
      male and 33 (54.1%) were female. Their median age was 28 years (range, 1.17-67
      years). The median duration from symptom onset to clinic visit time was 5 days
      (range, 1-16 days). Among these patients, 42 of them (68.9%) died. Of the
      confirmed cases, 18.0% did not present with fever. Patients aged >30 years had a
      higher fatality rate than those <30 years (87.0% vs 57.9%; P = .0175). The mean
      duration from symptom onset to clinic presentation of the survivors (4.57 +/-
      2.79 days) was shorter than that of the nonsurvivors (6.34 +/- 3.33 days).
      Clinical factors associated with a fatal outcome included weakness, extreme
      fatigue, vomiting, diarrhea, mental symptoms, bleeding, and loss of appetite. No
      statistical difference in the case fatality rate between males and females was
      found (P = .2061). CONCLUSIONS: The mortality of patients with EVD was closely
      associated with age and duration from symptom onset to presentation for care.
      Patients with EVD identified in the current outbreak did not necessarily have
      fever. Early diagnosis of the disease and timely symptomatic treatment may
      greatly contribute to the reduction of fatality rate of patients with EVD.

PMID- 25995208
TI  - Remarkably Divergent Regions Punctuate the Genome Assembly of the Caenorhabditis
      elegans Hawaiian Strain CB4856.
AB  - The Hawaiian strain (CB4856) of Caenorhabditis elegans is one of the most
      divergent from the canonical laboratory strain N2 and has been widely used in
      developmental, population, and evolutionary studies. To enhance the utility of
      the strain, we have generated a draft sequence of the CB4856 genome, exploiting a
      variety of resources and strategies. When compared against the N2 reference, the
      CB4856 genome has 327,050 single nucleotide variants (SNVs) and 79,529 insertion
      deletion events that result in a total of 3.3 Mb of N2 sequence missing from
      CB4856 and 1.4 Mb of sequence present in CB4856 but not present in N2. As
      previously reported, the density of SNVs varies along the chromosomes, with the
      arms of chromosomes showing greater average variation than the centers. In
      addition, we find 61 regions totaling 2.8 Mb, distributed across all six
      chromosomes, which have a greatly elevated SNV density, ranging from 2 to 16%
      SNVs. A survey of other wild isolates show that the two alternative haplotypes
      for each region are widely distributed, suggesting they have been maintained by
      balancing selection over long evolutionary times. These divergent regions contain
      an abundance of genes from large rapidly evolving families encoding F-box, MATH,
      BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors,
      suggesting that they provide selective advantages in natural environments. The
      draft sequence makes available a comprehensive catalog of sequence differences
      between the CB4856 and N2 strains that will facilitate the molecular dissection
      of their phenotypic differences. Our work also emphasizes the importance of going
      beyond simple alignment of reads to a reference genome when assessing differences
      between genomes.

PMID- 25995209
TI  - Sex-related differences in methods of and reasons for suicide in Turkey between
      1990 and 2010.
AB  - OBJECTIVE: To analyse suicides occurring in Turkey between 1990 and 2010
      according to sex, age, reason and method. METHODS: Data concerning suicides
      occurring in Turkey between 1990 and 2010 were obtained from annual records
      published by the Turkish Statistical Institute. Data were analysed according to
      sex, age, reason for suicide and suicide method. RESULTS: The crude suicide rate
      was 2.42 per 100 000 population in 1990 and 4.02 per 100 000 population in 2010.
      The highest number of suicides was seen in those aged 15-24 years. In this age
      group, the number of suicides in females was significantly higher than in males.
      The most common suicide method in Turkey was hanging. Men used firearms more
      frequently than women. All the reasons for suicide occurred in a higher number of
      males than females; however, the difference between males and females was more
      significant for economic problems, relationship problems and educational failure.
      The leading reason for suicide in females was relationship problems. CONCLUSION:
      Detecting population subgroups with a high suicide risk and obtaining regional
      demographic data are of great importance for future studies on suicide
      prevention.

PMID- 25995210
TI  - Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity.
AB  - Recent studies demonstrate that HDL's ability to promote cholesterol efflux from
      macrophages associates strongly with cardioprotection in humans independently of
      HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms
      that impair cholesterol efflux capacity during vascular disease are unclear.
      Inflammation, a well-established risk factor for cardiovascular disease, has been
      shown to impair HDL's cholesterol efflux capacity. We therefore tested the
      hypothesis that HDL's impaired efflux capacity is mediated by specific changes of
      its protein cargo. Humans with acute inflammation induced by low-level endotoxin
      had unchanged HDL-C levels, but their HDL-C efflux capacity was significantly
      impaired. Proteomic analyses demonstrated that HDL's cholesterol efflux capacity
      correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In
      mice, acute inflammation caused a marked impairment of HDL-C efflux capacity that
      correlated with a large increase in HDL SAA. In striking contrast, the efflux
      capacity of mouse inflammatory HDL was preserved with genetic ablation of SAA1
      and SAA2. Our observations indicate that the inflammatory impairment of HDL-C
      efflux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo.

PMID- 25995211
TI  - Feedback mechanisms for cardiac-specific microRNAs and cAMP signaling in
      electrical remodeling.
AB  - BACKGROUND: Loss of transient outward K(+) current (Ito) is well documented in
      cardiac hypertrophy and failure both in animal models and in humans. Electrical
      remodeling contributes to prolonged action potential duration and increased
      incidence of arrhythmias. Furthermore, there is a growing body of evidence
      linking microRNA (miR) dysregulation to the progression of both conditions. In
      this study, we examined the mechanistic basis underlying miR dysregulation in
      electrical remodeling and revealed a novel interaction with the adrenergic
      signaling pathway. METHODS AND RESULTS: We first used a tissue-specific knockout
      model of Dicer1 in cardiomyocytes to reveal the overall regulatory effect of miRs
      on the ionic currents and action potentials. We then validated the inducible cAMP
      early repressor as a target of miR-1 and took advantage of a clinically relevant
      model of post myocardial infarction and miR delivery to probe the mechanistic
      basis of miR dysregulation in electrical remodeling. These experiments revealed
      the role of inducible cAMP early repressor as a repressor of miR-1 and Ito,
      leading to prolonged action potential duration post myocardial infarction. In
      addition, delivery of miR-1 and miR-133a suppressed inducible cAMP early
      repressor expression and prevented both electrical remodeling and hypertrophy.
      CONCLUSIONS: Taken together, our results illuminate the mechanistic links between
      miRs, adrenergic signaling, and electrical remodeling. They also serve as a proof
      of-concept for the therapeutic potential of miR delivery post myocardial
      infarction.

PMID- 25995213
TI  - Predicting the burden of acute myocardial infarction in a country with limited
      resources: combining data from routine sources.
AB  - BACKGROUND: Prior to implementation of a national surveillance system for
      cardiovascular disease in Barbados, a small island state with limited health
      resources, the national burden of acute myocardial infarction (MI) was unknown.
      METHODS: We retrospectively estimated national acute MI incidence rates (IRs) per
      100,000 during the decade before registry implementation (1999-2008), using
      easily accessible routine data from different sources, assessing changes over
      time through Poisson regression. Future events (2009-2013) were estimated using
      simple sensitivity analysis to incorporate prediction uncertainty. Model
      predictions were compared with actual IRs from initial years of the registry.
      RESULTS: In 2000, crude IR was 85.5 (95% CI: 74.9-97.2), rising to 92.1 (81.2
      103.9) in 2008. Accounting for population ageing, the model anticipated IR of
      115.9 in 2010 (99.7-132.1), vs actual crude IR 129.7 (115.9-144.6). CONCLUSIONS:
      Despite no electronic medical record system in Barbados, data were simple to
      collect, and provided a rough baseline for acute MI burden. We show that, in
      countries with small populations, limited resources and in absence of
      surveillance, national mortality statistics and routine hospital data can be
      combined to adequately model national estimates of acute MI incidence. This cheap
      and simple, yet fairly accurate method could be a key tool for other low-resource
      countries with ageing populations and increasing cardiovascular disease levels.

PMID- 25995212
TI  - Worldwide Population Structure, Long-Term Demography, and Local Adaptation of
      Helicobacter pylori.
AB  - Helicobacter pylori is an important human pathogen associated with serious
      gastric diseases. Owing to its medical importance and close relationship with its
      human host, understanding genomic patterns of global and local adaptation in H.
      pylori may be of particular significance for both clinical and evolutionary
      studies. Here we present the first such whole genome analysis of 60 globally
      distributed strains, from which we inferred worldwide population structure and
      demographic history and shed light on interesting global and local events of
      positive selection, with particular emphasis on the evolution of San-associated
      lineages. Our results indicate a more ancient origin for the association of
      humans and H. pylori than previously thought. We identify several important
      perspectives for future clinical research on candidate selected regions that
      include both previously characterized genes (e.g., transcription elongation
      factor NusA and tumor necrosis factor alpha-inducing protein Tipalpha) and
      hitherto unknown functional genes.

PMID- 25995215
TI  - FESSH Abstracts.

PMID- 25995214
TI  - The interrelation between intestinal parasites and latent TB infections among
      newly resettled refugees in Texas.
AB  - BACKGROUND: Previous research has documented that parasite infection may increase
      vulnerability to TB among certain at risk populations. The purpose of this study
      was to identify whether an association exists between latent tuberculosis
      infection (LTBI) and intestinal parasite infection among newly resettled refugees
      in Texas while controlling for additional effects of region of origin, age and
      sex. METHODS: Data for all refugees screened for both TB and intestinal parasites
      between January 2010 and mid-October 2013 were obtained from the Texas Refugee
      Health Screening Program and were analyzed using logistic regression. RESULTS: A
      total of 9860 refugees were included. In multivariable logistic regression
      analysis, pathogenic and non-pathogenic intestinal parasite infections yielded
      statistically significant reduced odds of LTBI. However, when individual parasite
      species were analyzed, hookworm infection indicated statistically significant
      increased odds of LTBI (OR 1.674, CI: 1.126-2.488). DISCUSSION: A positive
      association exists between hookworm infection and LTBI in newly arrived refugees
      to Texas. More research is needed to assess the nature and extent of these
      associations.

PMID- 25995217
TI  - Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and
      alter cytokine expression in the gastric mucosa.
AB  - Colonization of the gastric mucosa by Helicobacter pylori can lead to peptic
      ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the
      recognition of microorganisms, and polymorphisms in their genes may influence the
      innate and adaptive immune response to H. pylori, affecting the clinical outcomes
      of the infection. We assessed the association between single nucleotide
      polymorphisms in TLR9 and TLR5 and gastroduodenal diseases. All patients were
      genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and 
      1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in
      duodenal ulcer and showed an association of risk with this pathology.
      Polymorphisms in TLR5 were not found to be associated with disease. Patients with
      polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1beta
      and TNF-alpha, whereas polymorphisms in TLR5 also decreased the expression of IL
      6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the
      risk for the development of duodenal ulcer probably by modifying the inflammatory
      response to H. pylori infection. This is the first study to show an association
      of 2848A allele of TLR9 with duodenal ulcer and with altered expression of
      inflammatory cytokines in the gastric mucosa.

PMID- 25995219
TI  - New blood: Creative funding of disease-specific research.

PMID- 25995218
TI  - Potential research participants support the return of raw sequence data.
AB  - Health-related results that are discovered in the process of genomic research
      should only be returned to research participants after being clinically validated
      and then delivered and followed up within a health service. Returning such
      results may be difficult for genomic researchers who are limited by resources or
      unable to access appropriate clinicians. Raw sequence data could, in theory, be
      returned instead. This might appear nonsensical as, on its own, it is a
      meaningless code with no clinical value. Yet, as and when direct to consumer
      genomics services become more widely available (and can be endorsed by
      independent health professionals and genomic researchers alike), the return of
      such data could become a realistic proposition. We explore attitudes from <7000
      members of the public, genomic researchers, genetic health professionals and non
      genetic health professionals and ask participants to suggest what they would do
      with a raw sequence, if offered it. Results show 62% participants were interested
      in using it to seek out their own clinical interpretation. Whilst we do not
      propose that raw sequence data should be returned at the moment, we suggest that
      should this become feasible in the future, participants of sequencing studies may
      possibly support this. 

PMID- 25995220
TI  - One integrin to rule them all?
AB  - Myofibroblast-derived alphavbeta1 integrin has emerged as a critical mediator of
      transforming growth factor-beta activation in experimental models of tissue
      fibrosis (Reed et al., this issue). 

PMID- 25995221
TI  - Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract
      and sexually transmitted bacterial infections.
AB  - The antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis
      with a unique mechanism of action and an excellent safety index, but it lacks
      antibacterial activity against most clinically important pathogens. A series of N
      benzyl-substituted 3'-(R)-3'-aminomethyl-3'-hydroxy spectinomycins was developed
      on the basis of a computational analysis of the aminomethyl spectinomycin binding
      site and structure-guided synthesis. These compounds had ribosomal inhibition
      values comparable to spectinomycin but showed increased potency against the
      common respiratory tract pathogens Streptococcus pneumoniae, Haemophilus
      influenzae, Legionella pneumophila, and Moraxella catarrhalis, as well as the
      sexually transmitted bacteria Neisseria gonorrhoeae and Chlamydia trachomatis.
      Non-ribosome-binding 3'-(S) isomers of the lead compounds demonstrated weak
      inhibitory activity in in vitro protein translation assays and poor antibacterial
      activity, indicating that the antibacterial activity of the series remains on
      target against the ribosome. Compounds also demonstrated no mammalian
      cytotoxicity, improved microsomal stability, and favorable pharmacokinetic
      properties in rats. The lead compound from the series exhibited excellent
      chemical stability superior to spectinomycin; no interaction with a panel of
      human receptors and drug metabolism enzymes, suggesting low potential for adverse
      reactions or drug-drug interactions in vivo; activity in vitro against a panel of
      penicillin-, macrolide-, and cephalosporin-resistant S. pneumoniae clinical
      isolates; and the ability to cure mice of fatal pneumococcal pneumonia and sepsis
      at a dose of 5 mg/kg. Together, these studies indicate that N-benzyl aminomethyl
      spectinomycins are suitable for further development to treat drug-resistant
      respiratory tract and sexually transmitted bacterial infections. 

PMID- 25995222
TI  - Targeting phosphatase-dependent proteoglycan switch for rheumatoid arthritis
      therapy.
AB  - Despite the availability of several therapies for rheumatoid arthritis (RA) that
      target the immune system, a large number of RA patients fail to achieve
      remission. Joint-lining cells, called fibroblast-like synoviocytes (FLS), become
      activated during RA and mediate joint inflammation and destruction of cartilage
      and bone. We identify RPTPsigma, a transmembrane tyrosine phosphatase, as a
      therapeutic target for FLS-directed therapy. RPTPsigma is reciprocally regulated
      by interactions with chondroitin sulfate or heparan sulfate containing
      extracellular proteoglycans in a mechanism called the proteoglycan switch. We
      show that the proteoglycan switch regulates FLS function. Incubation of FLS with
      a proteoglycan-binding RPTPsigma decoy protein inhibited cell invasiveness and
      attachment to cartilage by disrupting a constitutive interaction between
      RPTPsigma and the heparan sulfate proteoglycan syndecan-4. RPTPsigma mediated the
      effect of proteoglycans on FLS signaling by regulating the phosphorylation and
      cytoskeletal localization of ezrin. Furthermore, administration of the RPTPsigma
      decoy protein ameliorated in vivo human FLS invasiveness and arthritis severity
      in the K/BxN serum transfer model of RA. Our data demonstrate that FLS are
      regulated by an RPTPsigma-dependent proteoglycan switch in vivo, which can be
      targeted for RA therapy. We envision that therapies targeting the proteoglycan
      switch or its intracellular pathway in FLS could be effective as a monotherapy or
      in combination with currently available immune-targeted agents to improve control
      of disease activity in RA patients. 

PMID- 25995223
TI  - The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage
      target of febrifugine and its analogs.
AB  - The emergence of drug resistance is a major limitation of current antimalarials.
      The discovery of new druggable targets and pathways including those that are
      critical for multiple life cycle stages of the malaria parasite is a major goal
      for developing next-generation antimalarial drugs. Using an integrated
      chemogenomics approach that combined drug resistance selection, whole-genome
      sequencing, and an orthogonal yeast model, we demonstrate that the cytoplasmic
      prolyl-tRNA (transfer RNA) synthetase (PfcPRS) of the malaria parasite Plasmodium
      falciparum is a biochemical and functional target of febrifugine and its
      synthetic derivative halofuginone. Febrifugine is the active principle of a
      traditional Chinese herbal remedy for malaria. We show that treatment with
      febrifugine derivatives activated the amino acid starvation response in both P.
      falciparum and a transgenic yeast strain expressing PfcPRS. We further
      demonstrate in the Plasmodium berghei mouse model of malaria that halofuginol, a
      new halofuginone analog that we developed, is active against both liver and
      asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone
      and febrifugine, is well tolerated at efficacious doses and represents a
      promising lead for the development of dual-stage next-generation antimalarials. 

PMID- 25995224
TI  - Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable
      antitumor immunity in the bone marrow in multiple myeloma.
AB  - Successful adoptive T cell therapy (ACT) requires the ability to activate tumor
      specific T cells with the ability to traffic to the tumor site and effectively
      kill their target as well as persist over time. We hypothesized that ACT using
      marrow-infiltrating lymphocytes (MILs) in multiple myeloma (MM) could impart
      greater antitumor immunity in that they were obtained from the tumor
      microenvironment. We describe the results from the first clinical trial using
      MILs in MM. Twenty-five patients with either newly diagnosed or relapsed disease
      had their MILs harvested, activated and expanded, and subsequently infused on the
      third day after myeloablative therapy. Cells were obtained and adequately
      expanded in all patients with anti-CD3/CD28 beads plus interleukin-2, and a
      median of 9.5 * 10(8) MILs were infused. Factors indicative of response to MIL
      ACT included (i) the presence of measurable myeloma-specific activity of the ex
      vivo expanded product, (ii) low endogenous bone marrow T cell interferon-gamma
      production at baseline, (iii) a CD8(+) central memory phenotype at baseline, and
      (iv) the generation and persistence of myeloma-specific immunity in the bone
      marrow at 1 year after ACT. Achieving at least a 90% reduction in disease burden
      significantly increased the progression-free survival (25.1 months versus 11.8
      months; P = 0.01). This study demonstrates the feasibility and efficacy of MILs
      as a form of ACT with applicability across many hematologic malignancies and
      possibly solid tumors infiltrating the bone marrow. 

PMID- 25995225
TI  - The alphavbeta1 integrin plays a critical in vivo role in tissue fibrosis.
AB  - Integrins are transmembrane heterodimeric receptors that contribute to diverse
      biological functions and play critical roles in many human diseases. Studies
      using integrin subunit knockout mice and inhibitory antibodies have identified
      important roles for nearly every integrin heterodimer and led to the development
      of a number of potentially useful therapeutics. One notable exception is the
      alphavbeta1 integrin. alphav and beta1 subunits are individually present in
      numerous dimer pairs, making it challenging to infer specific roles for
      alphavbeta1 by genetic inactivation of individual subunits, and alphavbeta1
      complex-specific blocking antibodies do not yet exist. We therefore developed a
      potent and highly specific small-molecule inhibitor of alphavbeta1 to probe the
      function of this understudied integrin. We found that alphavbeta1, which is
      highly expressed on activated fibroblasts, directly binds to the latency
      associated peptide of transforming growth factor-beta1 (TGFbeta1) and mediates
      TGFbeta1 activation. Therapeutic delivery of this alphavbeta1 inhibitor
      attenuated bleomycin-induced pulmonary fibrosis and carbon tetrachloride-induced
      liver fibrosis, suggesting that drugs based on this lead compound could be
      broadly useful for treatment of diseases characterized by excessive tissue
      fibrosis. 

PMID- 25995226
TI  - Prolonged exposure to acetaminophen reduces testosterone production by the human
      fetal testis in a xenograft model.
AB  - Most common male reproductive disorders are linked to lower testosterone exposure
      in fetal life, although the factors responsible for suppressing fetal
      testosterone remain largely unknown. Protracted use of acetaminophen during
      pregnancy is associated with increased risk of cryptorchidism in sons, but
      effects on fetal testosterone production have not been demonstrated. We used a
      validated xenograft model to expose human fetal testes to clinically relevant
      doses and regimens of acetaminophen. Exposure to a therapeutic dose of
      acetaminophen for 7 days significantly reduced plasma testosterone (45%
      reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen
      exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal
      testis xenografts, whereas acetaminophen exposure for just 1 day did not alter
      either parameter. Plasma acetaminophen concentrations (at 1 hour after the final
      dose) in exposed host mice were substantially below those reported in humans
      after a therapeutic oral dose. Subsequent in utero exposure studies in rats
      indicated that the acetaminophen-induced reduction in testosterone likely results
      from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our
      results suggest that protracted use of acetaminophen (1 week) may suppress fetal
      testosterone production, which could have adverse consequences. Further studies
      are required to establish the dose-response and treatment-duration relationships
      to delineate the maximum dose and treatment period without this adverse effect. 

PMID- 25995228
TI  - Computer vision-based automated peak picking applied to protein NMR spectra.
AB  - MOTIVATION: A detailed analysis of multidimensional NMR spectra of macromolecules
      requires the identification of individual resonances (peaks). This task can be
      tedious and time-consuming and often requires support by experienced users.
      Automated peak picking algorithms were introduced more than 25 years ago, but
      there are still major deficiencies/flaws that often prevent complete and error
      free peak picking of biological macromolecule spectra. The major challenges of
      automated peak picking algorithms is both the distinction of artifacts from real
      peaks particularly from those with irregular shapes and also picking peaks in
      spectral regions with overlapping resonances which are very hard to resolve by
      existing computer algorithms. In both of these cases a visual inspection approach
      could be more effective than a 'blind' algorithm. RESULTS: We present a novel
      approach using computer vision (CV) methodology which could be better adapted to
      the problem of peak recognition. After suitable 'training' we successfully
      applied the CV algorithm to spectra of medium-sized soluble proteins up to
      molecular weights of 26 kDa and to a 130 kDa complex of a tetrameric membrane
      protein in detergent micelles. Our CV approach outperforms commonly used
      programs. With suitable training datasets the application of the presented method
      can be extended to automated peak picking in multidimensional spectra of nucleic
      acids or carbohydrates and adapted to solid-state NMR spectra. AVAILABILITY AND
      IMPLEMENTATION: CV-Peak Picker is available upon request from the authors.
      CONTACT: gsw@mol.biol.ethz.ch; michal.walczak@mol.biol.ethz.ch;
      adam.gonczarek@pwr.edu.pl SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25995227
TI  - Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in
      Rats With Acute Myocardial Infarction.
AB  - BACKGROUND: Although c-kit(pos) cardiac stem cells (CSCs) preserve left
      ventricular (LV) function and structure after myocardial infarction, CSC doses
      have been chosen arbitrarily, and the dose-effect relationship is unknown.
      METHODS AND RESULTS: Rats underwent a 90-minute coronary occlusion followed by 35
      days of reperfusion. Vehicle or CSCs at 5 escalating doses (0.3*10(6),
      0.75*10(6), 1.5*10(6), 3.0*10(6), and 6.0*10(6) cells/heart) were given
      intracoronarily 4 h after reperfusion. The lowest dose (0.3*10(6)) had no effect
      on LV function and morphology, whereas 0.75, 1.5, and 3.0*10(6) significantly
      improved regional and global LV function (echocardiography and hemodynamic
      studies). These 3 doses had similar effects on echocardiographic parameters
      (infarct wall thickening fraction, LV end-systolic and end-diastolic volumes, LV
      ejection fraction) and hemodynamic variables (LV end-diastolic pressure, LV
      dP/dtmax, preload adjusted maximal power, end-systolic elastance, preload
      recruitable stroke work) and produced similar reductions in apoptosis, scar size,
      infarct wall thinning, and LV expansion index and similar increases in viable
      myocardium in the risk region (morphometry). Infusion of 6.0*10(6) CSCs markedly
      increased postprocedural mortality. Green fluorescent protein and 5-bromo-2'
      deoxyuridine staining indicated that persistence of donor cells and formation of
      new myocytes were negligible with all doses. CONCLUSIONS: Surprisingly, in this
      rat model of acute myocardial infarction, the dose-response relationship for
      intracoronary CSCs is flat. A minimal dose between 0.3 and 0.75*10(6) is
      necessary for efficacy; above this threshold, a 4-fold increase in cell number
      does not produce greater improvement in LV function or structure. Further
      increases in cell dose are harmful.

PMID- 25995229
TI  - agplus: a rapid and flexible tool for aggregation plots.
AB  - Aggregation plots are frequently used to evaluate signal distributions at user
      interested points in ChIP-Seq data analysis. agplus, a new and simple command
      line tool, enables rapid and flexible generation of text tables tailored for
      aggregation plots from which users can easily design multiple groups based on
      user-definitions such as regulatory regions or transcription initiation sites.
      AVAILABILITY AND IMPLEMENTATION: This software is implemented in Ruby, supported
      on Linux and Mac OSX, and freely available at http://github.com/kazumits/agplus
      CONTACT: yohkawa@epigenetics.med.kyushu-u.ac.jp.

PMID- 25995230
TI  - Trans-species learning of cellular signaling systems with bimodal deep belief
      networks.
AB  - MOTIVATION: Model organisms play critical roles in biomedical research of human
      diseases and drug development. An imperative task is to translate
      information/knowledge acquired from model organisms to humans. In this study, we
      address a trans-species learning problem: predicting human cell responses to
      diverse stimuli, based on the responses of rat cells treated with the same
      stimuli. RESULTS: We hypothesized that rat and human cells share a common signal
      encoding mechanism but employ different proteins to transmit signals, and we
      developed a bimodal deep belief network and a semi-restricted bimodal deep belief
      network to represent the common encoding mechanism and perform trans-species
      learning. These 'deep learning' models include hierarchically organized latent
      variables capable of capturing the statistical structures in the observed
      proteomic data in a distributed fashion. The results show that the models
      significantly outperform two current state-of-the-art classification algorithms.
      Our study demonstrated the potential of using deep hierarchical models to
      simulate cellular signaling systems. AVAILABILITY AND IMPLEMENTATION: The
      software is available at the following URL:
      http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available
      through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview,
      upon publication of the report by the organizers. CONTACT: xinghua@pitt.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25995231
TI  - ABC: a tool to identify SNVs causing allele-specific transcription factor binding
      from ChIP-Seq experiments.
AB  - MOTIVATION: Detection of allelic imbalances in ChIP-Seq reads is a powerful
      approach to identify functional non-coding single nucleotide variants (SNVs),
      either polymorphisms or mutations, which modulate the affinity of transcription
      factors for chromatin. We present ABC, a computational tool that identifies
      allele-specific binding of transcription factors from aligned ChIP-Seq reads at
      heterozygous SNVs. ABC controls for potential false positives resulting from
      biases introduced by the use of short sequencing reads in ChIP-Seq and can
      efficiently process a large number of heterozygous SNVs. RESULTS: ABC
      successfully identifies previously characterized functional SNVs, such as the
      rs4784227 breast cancer risk associated SNP that modulates the affinity of FOXA1
      for the chromatin. AVAILABILITY AND IMPLEMENTATION: The code is open-source under
      an Artistic-2.0 license and versioned on GitHub
      (https://github.com/mlupien/ABC/). ABC is written in PERL and can be run on any
      platform with both PERL (>=5.18.1) and R (>=3.1.1) installed. The script requires
      the PERL Statistics::R module. CONTACT: mlupien@uhnres.utoronto.ca SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25995232
TI  - When less is more: 'slicing' sequencing data improves read decoding accuracy and
      de novo assembly quality.
AB  - MOTIVATION: As the invention of DNA sequencing in the 70s, computational
      biologists have had to deal with the problem of de novo genome assembly with
      limited (or insufficient) depth of sequencing. In this work, we investigate the
      opposite problem, that is, the challenge of dealing with excessive depth of
      sequencing. RESULTS: We explore the effect of ultra-deep sequencing data in two
      domains: (i) the problem of decoding reads to bacterial artificial chromosome
      (BAC) clones (in the context of the combinatorial pooling design we have recently
      proposed), and (ii) the problem of de novo assembly of BAC clones. Using real
      ultra-deep sequencing data, we show that when the depth of sequencing increases
      over a certain threshold, sequencing errors make these two problems harder and
      harder (instead of easier, as one would expect with error-free data), and as a
      consequence the quality of the solution degrades with more and more data. For the
      first problem, we propose an effective solution based on 'divide and conquer': we
      'slice' a large dataset into smaller samples of optimal size, decode each slice
      independently, and then merge the results. Experimental results on over 15 000
      barley BACs and over 4000 cowpea BACs demonstrate a significant improvement in
      the quality of the decoding and the final assembly. For the second problem, we
      show for the first time that modern de novo assemblers cannot take advantage of
      ultra-deep sequencing data. AVAILABILITY AND IMPLEMENTATION: Python scripts to
      process slices and resolve decoding conflicts are available from
      http://goo.gl/YXgdHT; software Hashfilter can be downloaded from
      http://goo.gl/MIyZHs CONTACT: stelo@cs.ucr.edu or timothy.close@ucr.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25995233
TI  - Role Differentiation in an Adolescent Victim-Offender Typology: Results From
      Medellin, Colombia.
AB  - The present study evaluates adolescent victimization and offending using cross
      sectional survey data from 1,475 adolescents living in a disadvantaged Comuna in
      Medellin, Colombia, while paying particular attention to the ways in which both
      victimization and violent offending are operationalized. We find that 37% of
      respondents experienced no lifetime victimization, while 60% experienced
      vicarious, and 4% personal victimization. When restricting violent offending to
      behavior involving a weapon, the majority of offenders (81%) also experienced
      victimization while only 33% of victims were also weapons offenders. Our final
      analysis seeks to identify theoretical conditions which differentiate roles in a
      victim-offender typology, a result we determine varies significantly depending on
      how "violent offending" is measured.

PMID- 25995234
TI  - A retrospective observational analysis to identify patient and treatment-related
      predictors of outcomes in a community mental health programme.
AB  - OBJECTIVES: This study aims to identify patient and treatment factors that affect
      clinical outcomes of community psychological therapy through the development of a
      predictive model using historic data from 2 services in London. In addition, the
      study aims to assess the completeness of data collection, explore how treatment
      outcomes are discriminated using current criteria for classifying recovery, and
      assess the feasibility and need for undertaking a future larger population
      analysis. DESIGN: Observational, retrospective discriminant analysis. SETTING: 2
      London community mental health services that provide psychological therapies for
      common mental disorders including anxiety and depression. PARTICIPANTS: A total
      of 7388 patients attended the services between February 2009 and May 2012, of
      which 4393 (59%) completed therapy, or there was an agreement to end therapy, and
      were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Different
      combinations of the clinical outcome scores for anxiety Generalised Anxiety
      Disorder-7 and depression Patient Health Questionnaire-9 were used to construct
      different treatment outcomes. RESULTS: The predictive models were able to assign
      a positive or negative clinical outcome to each patient based on 5 independent
      pre-treatment variables, with an accuracy of 69.4% and 79.3%, respectively:
      initial severity of anxiety and depression, ethnicity, deprivation and gender.
      The number of sessions attended/missed were also important factors identified in
      recovery. CONCLUSIONS: Predicting whether patients are likely to have a positive
      outcome following treatment at entry might allow suitable modification of
      scheduled treatment, possibly resulting in improvements in outcomes. The model
      also highlights factors not only associated with poorer outcomes but inextricably
      linked to prevalence of common mental disorders, emphasising the importance of
      social determinants not only in poor health but also poor recovery.

PMID- 25995235
TI  - Values in breast cancer screening: an empirical study with Australian experts.
AB  - OBJECTIVE: To explore what Australian experts value in breast screening, how
      these values are conceptualised and prioritised, and how they inform experts'
      reasoning and judgement about the Australian breast-screening programme. DESIGN:
      Qualitative study based on interviews with experts. PARTICIPANTS: 33 experts,
      including clinicians, programme managers, policymakers, advocates and researchers
      selected for their recognisable influence in the Australian breast-screening
      setting. SETTING: Australian breast-screening policy, practice and research
      settings. RESULTS: Experts expressed 2 types of values: ethical values (about
      what was good, important or right) and epistemological values (about how evidence
      should be created and used). Ethical values included delivering benefit, avoiding
      harm, promoting autonomy, fairness, cost effectiveness, accountability,
      professionalism and transparency. Epistemological values informed experts'
      arguments about prioritising and evaluating evidence methodology, source
      population and professional interests. Some values were conceptualised
      differently by experts: for example, delivering benefit could mean reducing
      breast cancer mortality, reducing all-cause mortality, reducing mortality in
      younger women, reducing need for aggressive treatment, and/or reassuring women
      they were cancer free. When values came into conflict, experts prioritised them
      differently: for example, when experts perceived a conflict between delivering
      benefits and promoting autonomy, there were differences in which value was
      prioritised. We explain the complexity of the relationship between held values
      and experts' overall views on breast cancer screening. CONCLUSIONS: Experts'
      positions in breast screening are influenced by evidence and a wide range of
      ethical and epistemological values. We conclude that discussions about values
      should be a regular part of breast-screening review in order to build
      understanding between those who hold different positions, and provide a mechanism
      for responding to these differences.

PMID- 25995237
TI  - Patients' adherence-related beliefs about methotrexate: a qualitative study of
      the role of written patient information.
AB  - OBJECTIVES: Methotrexate is effective in treating inflammatory arthritis, but
      both underadherence and overadherence can put patients at risk. Patients may fail
      to adhere due to practicalities including the unusual weekly dosing regimen, but
      medication beliefs also play a role. This study explored how both beliefs about
      necessity and concerns about methotrexate become established in patients with
      inflammatory arthritis and how patients use information in managing their beliefs
      and concerns. DESIGN: Semistructured interviews were conducted with patients
      taking oral methotrexate for inflammatory arthritis. Interviews were transcribed
      verbatim and analysed thematically. SETTING: Participants were recruited from a
      single Trust in the East Midlands. PARTICIPANTS: Fifteen patients (4 male, 11
      female) with inflammatory arthritis. RESULTS: Methotrexate was commonly
      prescribed at the time of diagnosis; at this point, experience of illness was
      influential for beliefs about medication necessity. Following prescription,
      patients absorbed information from written and verbal sources which reinforced
      beliefs about necessity but also raised concerns, including fear of side effects.
      Over time, beliefs were modified on the basis of personal experience,
      particularly of medication effectiveness and side effects. Some patients
      described tensions and dissonance in their beliefs and experiences of
      methotrexate, which put them at risk of non-adherence. Patients used information
      seeking and information-avoidance as strategies to resolve these tensions. The
      available information did little to help suppress dissonance and sometimes
      exacerbated it. CONCLUSIONS: Patients' experiences of coming to terms with taking
      methotrexate are complex, and their experiences of dissonance are particularly
      problematic. Experiences might be improved by supporting patients to assess
      necessity (particularly in the presence of side effects) and by providing
      information to moderate unnecessary concerns. Improving recording and sharing of
      monitoring results may be one way to meet these needs.

PMID- 25995236
TI  - The impact of dietary habits and metabolic risk factors on cardiovascular and
      diabetes mortality in countries of the Middle East and North Africa in 2010: a
      comparative risk assessment analysis.
AB  - OBJECTIVE/DESIGN: We conducted a comparative risk assessment analysis to estimate
      the cardiometabolic disease (CMD) mortality attributable to 11 dietary and 4
      metabolic risk factors in 20 countries of the Middle East by age, sex and time.
      The national exposure distributions were obtained from a systematic search of
      multiple databases. Missing exposure data were estimated using a multilevel
      Bayesian hierarchical model. The aetiological effect of each risk factor on
      disease-specific mortality was obtained from clinical trials and observational
      studies. The number of disease-specific deaths was obtained from the 2010 Global
      Burden of Disease mortality database. Mortality due to each risk factor was
      determined using the population attributable fraction and total number of disease
      specific deaths. SETTING/POPULATION: Adult population in the Middle East by age,
      sex, country and time. RESULTS: Suboptimal diet was the leading risk factor for
      CMD mortality in 11 countries accounting for 48% (in Morocco) to 72% (in the
      United Arab Emirates) of CMD deaths. Non-optimal systolic blood pressure was the
      leading risk factor for CMD deaths in eight countries causing 45% (in Bahrain) to
      68% (in Libya) of CMD deaths. Non-optimal body mass index and fasting plasma
      glucose were the third and fourth leading risk factors for CMD mortality in most
      countries. Among individual dietary factors, low intake of fruits accounted for
      8% (in Jordan) to 21% (in Palestine) of CMD deaths and low intake of whole grains
      was responsible for 7% (in Palestine) to 22% (in the United Arab Emirates) of CMD
      deaths. Between 1990 and 2010, the CMD mortality attributable to most risk
      factors had decreased except for body mass index and trans-fatty acids.
      CONCLUSIONS: Our findings highlight key similarities and differences in the
      impact of the dietary and metabolic risk factors on CMD mortality in the
      countries of the Middle East and inform priorities for policy measures to prevent
      CMD.

PMID- 25995238
TI  - Cost-effectiveness of a nurse-led internet-based vascular risk factor management
      programme: economic evaluation alongside a randomised controlled clinical trial.
AB  - OBJECTIVE: To assess the cost-effectiveness of an internet-based, nurse-led
      vascular risk factor management programme in addition to usual care compared with
      usual care alone in patients with a clinical manifestation of a vascular disease.
      DESIGN: Cost-effectiveness analysis alongside a randomised controlled trial (the
      Internet-based vascular Risk factor Intervention and Self-management (IRIS)
      study). SETTING: Multicentre trial in a secondary and tertiary healthcare
      setting. PARTICIPANTS: 330 patients with a recent clinical manifestation of
      atherosclerosis in the coronary, cerebral, or peripheral arteries and with >=2
      treatable vascular risk factors not at goal. INTERVENTION: The intervention
      consisted of a personalised website with an overview and actual status of
      patients' vascular risk factors, and mail communication with a nurse practitioner
      via the website for 12 months. The intervention combined self-management support,
      monitoring of disease control and pharmacotherapy. MAIN OUTCOME MEASURES:
      Societal costs, quality-adjusted life-years (QALYs) and incremental cost
      effectiveness. RESULTS: Patients experienced equal health benefits, that is, 0.86
      vs 0.85 QALY (intervention vs usual care) at 1 year. Adjusting for baseline
      differences, the incremental QALY difference was -0.014 (95% CI -0.034 to 0.007).
      The intervention was associated with lower total costs (?4859 vs ?5078,
      difference ?219, 95% CI -?2301 to ?1825). The probability that the intervention
      is cost-effective at a threshold value of ?20,000/QALY, is 65%. At mean annual
      cost of ?220 per patient, the intervention is relatively cheap. CONCLUSIONS: An
      internet-based, nurse-led intervention in addition to usual care to improve
      vascular risk factors in patients with a clinical manifestation of a vascular
      disease does not result in a QALY gain at 1 year, but has a small effect on
      vascular risk factors and is associated with lower costs. TRIAL REGISTRATION
      NUMBER: NCT00785031.

PMID- 25995239
TI  - Psychosocial interventions for disruptive behavioural problems in children living
      in low- and middle-income countries: study protocol of a systematic review.
AB  - INTRODUCTION: Disruptive behaviour disorders (DBDs) are among the most common
      forms of child psychopathology and have serious long-term academic, social, and
      mental health consequences worldwide. Psychosocial treatments are the first line
      of evidence-based treatments for DBDs, yet their effectiveness often varies
      according to patient sociodemographic characteristics, practice setting, and
      implementation procedures. While a large majority of the world's children live in
      low- and middle-income countries (LMIC), most studies have evaluated psychosocial
      treatments for DBDs in high-income Anglo countries. METHODS AND ANALYSIS: The
      primary objective of this systematic review is to assess the effects of
      psychosocial treatments for DBDs in children and adolescents (under age 18)
      diagnosed with oppositional defiant disorder, conduct disorder, or other
      disruptive behavioural problems living in LMIC. The secondary objectives are to:
      (1) describe the range and types of psychosocial treatments used to address DBDs
      in LMIC and (2) identify key dissemination and implementation factors (adaptation
      processes, training/supervision processes, and financial costs). All controlled
      trials comparing psychosocial treatments versus waiting list, no treatment, or
      treatment as usual in children living in LMIC will be included. Studies will be
      identified using the methods outlined in the Preferred Reporting Items for
      Systematic reviews and Meta-Analyses (PRISMA) guidelines without restrictions on
      language, publication type, status, or date of publication. The primary outcome
      measures will be disruptive behavioural problems (eg, oppositionality, defiance,
      aggression or deceit). Secondary outcomes will be positive mental health outcomes
      (eg, prosocial behaviour), function impairment, institutionalisation (or
      hospitalisation), academic outcomes and caregiver outcomes. ETHICS AND
      DISSEMINATION: This study uses data from published studies; therefore ethical
      review is not required. Findings will be presented in a published manuscript.
      TRIAL REGISTRATION NUMBER: PROSPERO CRD42014015334.

PMID- 25995240
TI  - The outcomes of recent patient safety education interventions for trainee
      physicians and medical students: a systematic review.
AB  - OBJECTIVE: To systematically review the latest evidence for patient safety
      education for physicians in training and medical students, updating, extending
      and improving on a previous systematic review on this topic. DESIGN: A systematic
      review. DATA SOURCES: Embase, Ovid Medline and PsycINFO databases. STUDY
      SELECTION: Studies including an evaluation of patient safety training
      interventions delivered to trainees/residents and medical students published
      between January 2009 and May 2014. DATA EXTRACTION: The review was performed
      using a structured data capture tool. Thematic analysis also identified factors
      influencing successful implementation of interventions. RESULTS: We identified 26
      studies reporting patient safety interventions: 11 involving students and 15
      involving trainees/residents. Common educational content included a general
      overview of patient safety, root cause/systems-based analysis, communication and
      teamwork skills, and quality improvement principles and methodologies. The
      majority of courses were well received by learners, and improved patient safety
      knowledge, skills and attitudes. Moreover, some interventions were shown to
      result in positive behaviours, notably subsequent engagement in quality
      improvement projects. No studies demonstrated patient benefit. Availability of
      expert faculty, competing curricular/service demands and institutional culture
      were important factors affecting implementation. CONCLUSIONS: There is an
      increasing trend for developing educational interventions in patient safety
      delivered to trainees/residents and medical students. However, significant
      methodological shortcomings remain and additional evidence of impact on patient
      outcomes is needed. While there is some evidence of enhanced efforts to promote
      sustainability of such interventions, further work is needed to encourage their
      wider adoption and spread.

PMID- 25995241
TI  - Multiple sclerosis course and clinical outcomes in patients with comorbid asthma:
      a survey study.
AB  - OBJECTIVE: To determine if comorbid asthma is associated with accumulation of
      multiple sclerosis (MS)-related impairment and disability. METHOD: We sent a
      comprehensive questionnaire to a cohort of patients with MS and examined the
      association between comorbid asthma and reaching Expanded Disability Status Scale
      (EDSS) scores 4.0 and 6.0. Multiple Sclerosis Impact Scale (MSIS-29) scores were
      compared between patients with MS with and without comorbid asthma. RESULTS: 680
      patients participated in our study of whom 88 (12.9%) had comorbid asthma. There
      was no difference in the prevalence of asthma between our MS cohort and the
      England general population (OR: 0.89, 95% CI 0.68 to 1.17). We did not observe a
      significant association between having asthma and the risk of reaching EDSS
      scores 4.0 and 6.0 (HR: 1.29, 95% CI 0.93 to 1.77, and HR: 1.33, 95% CI 0.93 to
      1.89, respectively) after controlling for confounders. Patients with MS with
      asthma reported higher level of psychological impairments (coefficient: 2.29, 95%
      CI 0.1 to 4.49). CONCLUSIONS: Asthma is a prevalent condition among patients with
      MS and it may contribute to the psychological impairment in MS. Although we did
      not observe significant association between comorbid asthma and physical
      disability in MS, it seems that the two conditions influence one another.

PMID- 25995243
TI  - ADHD in Childhood and/or Adulthood as a Risk Factor for Domestic Violence or
      Intimate Partner Violence: A Systematic Review.
AB  - OBJECTIVE: To date, treatment programs for adult domestic violence (DV) or
      intimate partner violence (IPV) have had minimal impact. To make treatment more
      effective, programs should be adjusted to psychopathology of the offender. As
      emotional lability and poor emotional self-regulation and self-control are common
      features of ADHD, it may play a pivotal role as a predictor for adult DV/IPV.
      METHOD: This systematic review synthesizes the available evidence for childhood
      and/or adult ADHD being a risk factor for DV/IPV. RESULTS: Four case control
      studies and three cohort studies were included in the review. Although three case
      control studies showed positive associations between childhood and/or adult ADHD
      and adult DV/IPV, two did insufficiently control for the presence of comorbid
      Conduct Disorder (CD) or Antisocial Personality Disorder (ASPD). CONCLUSION:
      Cohort studies identified hyperactive, impulsive, and inattention symptoms as
      risk factors for adult IPV. CD and ASPD were regarded as mediators in three
      studies.

PMID- 25995242
TI  - Risk factors associated with purchasing pesticide from shops for self-poisoning:
      a protocol for a population-based case-control study.
AB  - INTRODUCTION: Pesticide self-poisoning is one of the most frequently used methods
      of suicide worldwide, killing over 300,000 people annually. Around 15-20% of
      pesticide self-poisonings occur soon after the person has bought the pesticide
      from a shop. We aim to determine the characteristics of individuals who purchase
      pesticides directly from shops and how they differ from individuals who access
      pesticides from other sources such as home, home garden or farmland. This
      information will help inform possible vendor/shop-based intervention strategies
      aimed at reducing access to pesticides used for self-harm. METHODS AND ANALYSIS:
      This study will investigate risk factors associated with purchasing pesticides
      for acts of self-poisoning from pesticide shops, including cases identified over
      a 9-month period using a population-based case-control group approach. Four
      interviewer-administered data collection tools will be used for this study: a
      semistructured questionnaire, Beck Suicidal Intent Scale (SIS), Clinical
      Interview Schedule-Sinhalese version (CIS-Sn) and Alcohol Use Disorders
      Identification Test (AUDIT). Each case (expected n=33) will be compared with two
      groups of individuals: (1) those who have self-poisoned using pesticides from the
      home, home garden or farmland and (2) those who bought pesticides from the same
      shops as the above cases, but not did not self-poison. Logistic regression models
      will be used to identify risk factors of purchasing pesticides for self-poisoning
      from shops. ETHICS AND DISSEMINATION: The study has received ethical approval
      from the Ethical Review Committee of the Faculty of Medicine and Allied Sciences,
      Rajarata University of Sri Lanka. A sensitive data collection technique will be
      used and ethical issues will be considered throughout the study. Results will be
      disseminated in scientific peer-reviewed articles.

PMID- 25995244
TI  - Adaptive Mutations Enhance Assembly and Cell-to-Cell Transmission of a High-Titer
      Hepatitis C Virus Genotype 5a Core-NS2 JFH1-Based Recombinant.
AB  - Recombinant hepatitis C virus (HCV) clones propagated in human hepatoma cell
      cultures yield relatively low infectivity titers. Here, we adapted the JFH1-based
      Core-NS2 recombinant SA13/JFH1C3405G,A3696G (termed SA13/JFH1orig), of the poorly
      characterized genotype 5a, to Huh7.5 cells, yielding a virus with greatly
      improved spread kinetics and an infectivity titer of 6.7 log10 focus-forming
      units (FFU)/ml. We identified several putative adaptive amino acid changes. In
      head-to-head infections at fixed multiplicities of infection, one SA13/JFH1orig
      mutant termed SA13/JFH1Core-NS5B, containing 13 amino acid changes (R114W and
      V187A [Core]; V235L [E1]; T385P [E2]; L782V [p7]; Y900C [NS2]; N2034D, E2238G,
      V2252A, L2266P, and I2340T [NS5A]; A2500S and V2841A [NS5B]), displayed fitness
      comparable to that of the polyclonal high-titer adapted virus. Single-cycle virus
      production assays in CD81-deficient Huh7-derived cells demonstrated that these
      changes did not affect replication but increased HCV assembly and specific
      infectivity as early as 24 h posttransfection. Infectious coculture assays in
      Huh7.5 cells showed a significant increase in cell-to-cell transmission for
      SA13/JFH1Core-NS5B viruses as well as viruses with only p7 and nonstructural
      protein mutations. Interestingly, the E2 hypervariable region 1 (HVR1) mutation
      T385P caused (i) increased sensitivity to neutralizing patient IgG and human
      monoclonal antibodies AR3A and AR4A and (ii) increased accessibility of the CD81
      binding site without affecting the usage of CD81 and SR-BI. We finally
      demonstrated that SA13/JFH1orig and SA13/JFH1Core-NS5B, with and without the E2
      mutation T385P, displayed similar biophysical properties following iodixanol
      gradient ultracentrifugation. This study has implications for investigations
      requiring high virus concentrations, such as studies of HCV particle composition
      and development of whole-virus vaccine antigens. IMPORTANCE: Hepatitis C virus
      (HCV) is a major global health care burden, affecting more than 150 million
      people worldwide. These individuals are at high risk of developing severe end
      stage liver diseases. No vaccine exists. While it is possible to produce HCV
      particles resembling isolates of all HCV genotypes in human hepatoma cells
      (HCVcc), production efficacy varies. Thus, for several important studies,
      including vaccine development, in vitro systems enabling high-titer production of
      diverse HCV strains would be advantageous. Our study offers important functional
      data on how cell culture-adaptive mutations identified in genotype 5a JFH1-based
      HCVcc permit high-titer culture by affecting HCV genesis through increasing virus
      assembly and HCV fitness by enhancing the virus specific infectivity and cell-to
      cell transmission ability, without influencing the biophysical particle
      properties. High-titer HCVcc like the one described in this study may be pivotal
      in future vaccine-related studies where large quantities of infectious HCV
      particles are necessary.

PMID- 25995245
TI  - Interferon Beta and Interferon Alpha 2a Differentially Protect Head and Neck
      Cancer Cells from Vesicular Stomatitis Virus-Induced Oncolysis.
AB  - Oncolytic viruses (OV) preferentially kill cancer cells due in part to defects in
      their antiviral responses upon exposure to type I interferons (IFNs). However,
      IFN responsiveness of some tumor cells confers resistance to OV treatment. The
      human type I IFNs include one IFN-beta and multiple IFN-alpha subtypes that share
      the same receptor but are capable of differentially inducing biological
      responses. The role of individual IFN subtypes in promoting tumor cell resistance
      to OV is addressed here. Two human IFNs which have been produced for clinical
      use, IFN-alpha2a and IFN-beta, were compared for activity in protecting human
      head and neck squamous cell carcinoma (HNSCC) lines from oncolysis by vesicular
      stomatitis virus (VSV). Susceptibility of HNSCC lines to killing by VSV varied.
      VSV infection induced increased production of IFN-beta in resistant HNSCC cells.
      When added exogenously, IFN-beta was significantly more effective at protecting
      HNSCC cells from VSV oncolysis than was IFN-alpha2a. In contrast, normal
      keratinocytes and endothelial cells were protected equivalently by both IFN
      subtypes. Differential responsiveness of tumor cells to IFN-alpha and -beta was
      further supported by the finding that autocrine IFN-beta but not IFN-alpha
      promoted survival of HNSCC cells during persistent VSV infection. Therefore, IFN
      alpha and -beta differentially affect VSV oncolysis, justifying the evaluation
      and comparison of IFN subtypes for use in combination with VSV therapy. Pairing
      VSV with IFN-alpha2a may enhance selectivity of oncolytic VSV therapy for HNSCC
      by inhibiting VSV replication in normal cells without a corresponding inhibition
      in cancer cells. IMPORTANCE: There has been a great deal of progress in the
      development of oncolytic viruses. However, a major problem is that individual
      cancers vary in their sensitivity to oncolytic viruses. In many cases this is due
      to differences in their production and response to interferons (IFNs). The
      experiments described here compared the responses of head and neck squamous cell
      carcinoma cell lines to two IFN subtypes, IFN-alpha2a and IFN-beta, in protection
      from oncolytic vesicular stomatitis virus. We found that IFN-alpha2a was
      significantly less protective for cancer cells than was IFN-beta, whereas normal
      cells were equivalently protected by both IFNs. These results suggest that from a
      therapeutic standpoint, selectivity for cancer versus normal cells may be
      enhanced by pairing VSV with IFN-alpha2a.

PMID- 25995246
TI  - Tick Saliva Enhances Powassan Virus Transmission to the Host, Influencing Its
      Dissemination and the Course of Disease.
AB  - Powassan virus (POWV) is an encephalitic tick-borne flavivirus which can result
      in serious neuroinvasive disease with up to a 10% case fatality rate. The study
      objective was to determine whether the salivary gland extract (SGE) from Ixodes
      scapularis ticks facilitates the transmission and dissemination of POWV in a
      process known as saliva-activated transmission. Groups of BALB/c mice were
      footpad inoculated with either a high dose of POWV with and without SGE or a low
      dose of POWV with and without SGE. Mice from each group were sacrificed daily.
      Organ viral loads and gene expression profiles were evaluated by quantitative
      real-time PCR. Both groups of mice infected with high-dose POWV showed severe
      neurological signs of disease preceding death. The presence of SGE did not affect
      POWV transmission or disease outcome for mice infected with the high dose of
      POWV. Neuroinvasion, paralysis, and death occurred for all mice infected with the
      low dose of POWV plus SGE; however, for mice infected with the low dose of POWV
      in the absence of SGE, there were no clinical signs of infection and no mice
      succumbed to disease. Although this group displayed low-level viremias, all mice
      were completely healthy, and it was the only group in which POWV was cleared from
      the lymph nodes. We conclude that saliva-activated transmission occurs in mice
      infected with a low dose of POWV. Our study is the first to demonstrate virus
      dose-dependent saliva-activated transmission, warranting further investigation of
      the specific salivary factors responsible for enhancing POWV transmission.
      IMPORTANCE: Powassan virus (POWV) is a tick-borne flavivirus that continues to
      emerge in the United States, as is evident by the surge in number and expanding
      geographic range of confirmed cases in the past decade. This neuroinvasive virus
      is transmitted to humans by infected tick bites. Successful tick feeding is
      facilitated by a collection of pharmacologically active factors in tick saliva.
      In a process known as saliva-activated transmission, tick bioactive salivary
      molecules are thought to modulate the host environment, making it more favorable
      for the transmission and establishment of a pathogen. This phenomenon has been
      demonstrated for several tick-borne pathogens; however, a systematic
      investigation of the role of tick saliva on dissemination and pathogenesis of a
      tick-borne viral disease has never been attempted before. This study will fill
      that gap by systematically examining whether the presence of tick saliva
      contributes to the transmission and dissemination of POWV in mice.

PMID- 25995247
TI  - FUSE Binding Protein 1 Facilitates Persistent Hepatitis C Virus Replication in
      Hepatoma Cells by Regulating Tumor Suppressor p53.
AB  - Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver
      cirrhosis, and hepatocellular carcinoma (HCC). Immunohistochemistry of archived
      HCC tumors showed abundant FBP1 expression in HCC tumors with the CHC background.
      Oncomine data analysis of normal versus HCC tumors with the CHC background
      indicated a 4-fold increase in FBP1 expression with a concomitant 2.5-fold
      decrease in the expression of p53. We found that FBP1 promotes HCV replication by
      inhibiting p53 and regulating BCCIP and TCTP, which are positive and negative
      regulators of p53, respectively. The severe inhibition of HCV replication in FBP1
      knockdown Huh7.5 cells was restored to a normal level by downregulation of either
      p53 or BCCIP. Although p53 in Huh7.5 cells is transcriptionally inactive as a
      result of Y220C mutation, we found that the activation and DNA binding ability of
      Y220C p53 were strongly suppressed by FBP1 but significantly activated upon
      knockdown of FBP1. Transient expression of FBP1 in FBP1 knockdown cells fully
      restored the control phenotype in which the DNA binding ability of p53 was
      strongly suppressed. Using electrophoretic mobility shift assay (EMSA) and
      isothermal titration calorimetry (ITC), we found no significant difference in in
      vitro target DNA binding affinity of recombinant wild-type p53 and its Y220C
      mutant p53. However, in the presence of recombinant FBP1, the DNA binding ability
      of p53 is strongly inhibited. We confirmed that FBP1 downregulates BCCIP, p21,
      and p53 and upregulates TCTP under radiation-induced stress. Since FBP1 is
      overexpressed in most HCC tumors with an HCV background, it may have a role in
      promoting persistent virus infection and tumorigenesis. IMPORTANCE: It is our
      novel finding that FUSE binding protein 1 (FBP1) strongly inhibits the function
      of tumor suppressor p53 and is an essential host cell factor required for HCV
      replication. Oncomine data analysis of a large number of samples has revealed
      that overexpression of FBP1 in most HCC tumors with chronic hepatitis C is
      significantly linked with the decreased expression level of p53. The most
      significant finding is that FBP1 not only physically interacts with p53 and
      interferes with its binding to the target DNA but also functions as a negative
      regulator of p53 under cellular stress. FBP1 is barely detectable in normal
      differentiated cells; its overexpression in HCC tumors with the CHC background
      suggests that FBP1 has an important role in promoting HCV infection and HCC
      tumors by suppressing p53.

PMID- 25995249
TI  - Expanding regulatory T cells alleviates chikungunya virus-induced pathology in
      mice.
AB  - : Chikungunya virus (CHIKV) infection is a re-emerging pandemic human arboviral
      disease. CD4+ T cells were previously shown to contribute to joint inflammation
      in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody
      selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL
      2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs
      ameliorates CHIKV-induced joint pathology. It does so by inhibiting the
      infiltration of CD4+ T cells due to the induction of anergy in CHIKV-specific
      CD4+ effector T cells. These findings suggest that activation of Tregs could also
      become an alternative approach to control CHIKV-mediated disease. IMPORTANCE:
      Chikungunya virus (CHIKV) has re-emerged as a pathogen of global significance.
      Patients infected with CHIKV suffer from incapacitating joint pain that severely
      affects their daily functioning. Despite the best efforts, effective treatment is
      still inadequate. While T cells-mediated immunopathology in CHIKV infections has
      been reported, the role of regulatory T cells (Tregs) has not been explored. The
      JES6-1 anti-IL-2 antibody has been demonstrated to selectively expand mouse Tregs
      by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated
      expansion of Tregs ameliorates the CHIKV-induced joint pathology in mice by
      neutralizing virus-specific CD4+ effector T (Teff) cells. We show that this
      treatment abrogates the infiltration of pathogenic CD4+ T cells through induction
      of anergy in CHIKV-specific CD4+ Teff cells. This is the first evidence where the
      role of Tregs is demonstrated in CHIKV pathogenesis and its expansion could
      control virus-mediated immunopathology.

PMID- 25995248
TI  - Activated Nrf2 Interacts with Kaposi's Sarcoma-Associated Herpesvirus Latency
      Protein LANA-1 and Host Protein KAP1 To Mediate Global Lytic Gene Repression.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with
      Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric
      Castleman's disease. We have previously shown that KSHV utilizes the host
      transcription factor Nrf2 to aid in infection of endothelial cells and
      oncogenesis. Here, we investigate the role of Nrf2 in PEL and PEL-derived cell
      lines and show that KSHV latency induces Nrf2 protein levels and transcriptional
      activity through the COX-2/PGE2/EP4/PKCzeta axis. Next-generation sequencing of
      KSHV transcripts in the PEL-derived BCBL-1 cell line revealed that knockdown of
      this activated Nrf2 results in global elevation of lytic genes. Nrf2 inhibition
      by the chemical brusatol also induces lytic gene expression. Both Nrf2 knockdown
      and brusatol-mediated inhibition induced KSHV lytic reactivation in BCBL-1 cells.
      In a series of follow-up experiments, we characterized the mechanism of Nrf2
      mediated regulation of KSHV lytic repression during latency. Biochemical assays
      showed that Nrf2 interacted with KSHV latency-associated nuclear antigen 1 (LANA
      1) and the host transcriptional repressor KAP1, which together have been shown to
      repress lytic gene expression. Promoter studies showed that although Nrf2 alone
      induces the open reading frame 50 (ORF50) promoter, its association with LANA-1
      and KAP1 abrogates this effect. Interestingly, LANA-1 is crucial for efficient
      KAP1/Nrf2 association, while Nrf2 is essential for LANA-1 and KAP1 recruitment to
      the ORF50 promoter and its repression. Overall, these results suggest that
      activated Nrf2, LANA-1, and KAP1 assemble on the ORF50 promoter in a temporal
      fashion. Initially, Nrf2 binds to and activates the ORF50 promoter during early
      de novo infection, an effect that is exploited during latency by LANA-1-mediated
      recruitment of the host transcriptional repressor KAP1 on Nrf2. Cell death assays
      further showed that Nrf2 and KAP1 knockdown induce significant cell death in PEL
      cell lines. Our studies suggest that Nrf2 modulation through available oral
      agents is a promising therapeutic approach in the treatment of KSHV-associated
      malignancies. IMPORTANCE: KS and PEL are aggressive KSHV-associated malignancies
      with moderately effective, highly toxic chemotherapies. Other than ganciclovir
      and alpha interferon (IFN-alpha) prophylaxis, no KSHV-associated chemotherapy
      targets the underlying infection, a major oncogenic force. Hence, drugs that
      selectively target KSHV infection are necessary to eradicate the malignancy while
      sparing healthy cells. We recently showed that KSHV infection of endothelial
      cells activates the transcription factor Nrf2 to promote an environment conducive
      to infection and oncogenesis. Nrf2 is modulated through several well-tolerated
      oral agents and may be an important target in KSHV biology. Here, we investigate
      the role of Nrf2 in PEL and demonstrate that Nrf2 plays an important role in KSHV
      gene expression, lytic reactivation, and cell survival by interacting with the
      host transcriptional repressor KAP1 and the viral latency-associated protein LANA
      1 to mediate global lytic gene repression and thus cell survival. Hence,
      targeting Nrf2 with available therapies is a viable approach in the treatment of
      KSHV malignancies.

PMID- 25995250
TI  - Rethinking the Response to Emerging Microbes: Vaccines and Therapeutics in the
      Ebola Era--a Conference at Harvard Medical School.
AB  - Harvard Medical School convened a meeting of biomedical and clinical experts on 5
      March 2015 on the topic of "Rethinking the Response to Emerging Microbes:
      Vaccines and Therapeutics in the Ebola Era," with the goals of discussing the
      lessons from the recent Ebola outbreak and using those lessons as a case study to
      aid preparations for future emerging infections. The speakers and audience
      discussed the special challenges in combatting an infectious agent that causes
      sporadic outbreaks in resource-poor countries. The meeting led to a call for
      improved basic medical care for all and continued support of basic discovery
      research to provide the foundation for preparedness for future outbreaks in
      addition to the targeted emergency response to outbreaks and targeted research
      programs against Ebola virus and other specific emerging pathogens. 

PMID- 25995251
TI  - Varicella-Zoster Virus and Herpes Simplex Virus 1 Differentially Modulate NKG2D
      Ligand Expression during Productive Infection.
AB  - Natural killer (NK) cell-deficient patients are particularly susceptible to
      severe infection with herpesviruses, especially varicella-zoster virus (VZV) and
      herpes simplex virus 1 (HSV-1). The critical role that NK cells play in
      controlling these infections denotes an intricate struggle for dominance between
      virus and NK cell antiviral immunity; however, research in this area has remained
      surprisingly limited. Our study addressed this absence of knowledge and found
      that infection with VZV was not associated with enhanced NK cell activation,
      suggesting that the virus uses specific mechanisms to limit NK cell activity.
      Analysis of viral regulation of ligands for NKG2D, a potent activating receptor
      ubiquitously expressed on NK cells, revealed that VZV differentially modulates
      expression of the NKG2D ligands MICA, ULBP2, and ULBP3 by upregulating MICA
      expression while reducing ULBP2 and ULBP3 expression on the surface of infected
      cells. Despite being closely related to VZV, infection with HSV-1 produced a
      remarkably different effect on NKG2D ligand expression. A significant decrease in
      MICA, ULBP2, and ULBP3 was observed with HSV-1 infection at a total cellular
      protein level, as well as on the cell surface. We also demonstrate that HSV-1
      differentially regulates expression of an additional NKG2D ligand, ULBP1, by
      reducing cell surface expression while total protein levels are unchanged. Our
      findings illustrate both a striking point of difference between two closely
      related alphaherpesviruses, as well as suggest a powerful capacity for VZV and
      HSV-1 to evade antiviral NK cell activity through novel modulation of NKG2D
      ligand expression. IMPORTANCE: Patients with deficiencies in NK cell function
      experience an extreme susceptibility to infection with herpesviruses, in
      particular, VZV and HSV-1. Despite this striking correlation, research into
      understanding how these two alphaherpesviruses interact with NK cells is
      surprisingly limited. Through examination of viral regulation of ligands to the
      activating NK cell receptor NKG2D, we reveal patterns of modulation by VZV, which
      were unexpectedly varied in response to regulation by HSV-1 infection. Our study
      begins to unravel the undoubtedly complex interactions that occur between NK
      cells and alphaherpesvirus infection by providing novel insights into how VZV and
      HSV-1 manipulate NKG2D ligand expression to modulate NK cell activity, while also
      illuminating a distinct variation between two closely related alphaherpesviruses.

PMID- 25995252
TI  - A Transgenic Drosophila melanogaster Model To Study Human T-Lymphotropic Virus
      Oncoprotein Tax-1-Driven Transformation In Vivo.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1)-induced adult T-cell
      leukemia/lymphoma is an aggressive malignancy. HTLV-2 is genetically related to
      HTLV-1 but does not cause any malignant disease. HTLV-1 Tax transactivator (Tax
      1) contributes to leukemogenesis via NF-kappaB. We describe transgenic Drosophila
      models expressing Tax in the compound eye and plasmatocytes. We demonstrate that
      Tax-1 but not Tax-2 induces ommatidial perturbation and increased plasmatocyte
      proliferation and that the eye phenotype is dependent on Kenny (IKKgamma/NEMO),
      thus validating this new in vivo model. 

PMID- 25995254
TI  - Pseudorabies Virus Fast Axonal Transport Occurs by a pUS9-Independent Mechanism.
AB  - Reactivation from latency results in transmission of neurotropic herpesviruses
      from the nervous system to body surfaces, referred to as anterograde axonal
      trafficking. The virus-encoded protein pUS9 promotes axonal dissemination by
      sorting virus particles into axons, but whether it is also an effector of fast
      axonal transport within axons is unknown. To determine the role of pUS9 in
      anterograde trafficking, we analyzed the axonal transport of pseudorabies virus
      in the presence and absence of pUS9. 

PMID- 25995253
TI  - Cytokine-Mediated Activation of NK Cells during Viral Infection.
AB  - Natural killer (NK) cells provide a first line of defense against infection via
      the production of antiviral cytokines and direct lysis of target cells. Cytokines
      such as interleukin 12 (IL-12) and IL-18 are critical regulators of NK cell
      activation, but much remains to be learned about how cytokines interact to
      regulate NK cell function. Here, we have examined cytokine-mediated activation of
      NK cells during infection with two natural mouse pathogens, lymphocytic
      choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV). Using a
      systematic screen of 1,849 cytokine pairs, we identified the most potent
      combinations capable of eliciting gamma interferon (IFN-gamma) production in NK
      cells. We observed that NK cell responses to cytokine stimulation were reduced 8
      days after acute LCMV infection but recovered to preinfection levels by 60 days
      postinfection. In contrast, during MCMV infection, NK cell responses to cytokines
      remained robust at all time points examined. Ly49H-positive (Ly49H+) NK cells
      recognizing viral ligand m157 showed preferential proliferation during early MCMV
      infection. A population of these cells was still detected beyond 60 days
      postinfection, but these divided cells did not demonstrate enhanced IFN-gamma
      production in response to innate cytokine stimulation. Instead, the maturation
      state of the NK cells (as determined by CD11b or CD27 surface phenotype) was
      predictive of responsiveness to cytokines, regardless of Ly49H expression. These
      results help define cytokine interactions that regulate NK cell activation and
      highlight variations in NK cell function during two unrelated viral infections.
      IMPORTANCE: Natural killer cells play an important role in immunity to many viral
      infections. From an initial screen of 1,849 cytokine pairs, we identified the
      most stimulatory cytokine combinations capable of inducing IFN-gamma production
      by NK cells. Ly49H+ NK cells, which can be directly activated by MCMV protein
      m157, preferentially proliferated during MCMV infection but did not show enhanced
      IFN-gamma production following direct ex vivo cytokine stimulation. Instead,
      mature CD11b+ and/or CD27+ NK cells responded similarly to innate cytokine
      stimulation regardless of Ly49H expression. Collectively, our data provide a
      better foundation for understanding cytokine-mediated NK cell activation during
      viral infection.

PMID- 25995255
TI  - Respiratory Syncytial Virus Inhibitor AZ-27 Differentially Inhibits Different
      Polymerase Activities at the Promoter.
AB  - Respiratory syncytial virus (RSV) is the leading cause of pediatric respiratory
      disease. RSV has an RNA-dependent RNA polymerase that transcribes and replicates
      the viral negative-sense RNA genome. The large polymerase subunit (L) has
      multiple enzymatic activities, having the capability to synthesize RNA and add
      and methylate a cap on each of the viral mRNAs. Previous studies (H. Xiong et
      al., Bioorg Med Chem Lett, 23:6789-6793, 2013,
      http://dx.doi.org/10.1016/j.bmcl.2013.10.018; C. L. Tiong-Yip et al., Antimicrob
      Agents Chemother, 58:3867-3873, 2014, http://dx.doi.org/10.1128/AAC.02540-14) had
      identified a small-molecule inhibitor, AZ-27, that targets the L protein. In this
      study, we examined the effect of AZ-27 on different aspects of RSV polymerase
      activity. AZ-27 was found to inhibit equally both mRNA transcription and genome
      replication in cell-based minigenome assays, indicating that it inhibits a step
      common to both of these RNA synthesis processes. Analysis in an in vitro
      transcription run-on assay, containing RSV nucleocapsids, showed that AZ-27
      inhibits synthesis of transcripts from the 3' end of the genome to a greater
      extent than those from the 5' end, indicating that it inhibits transcription
      initiation. Consistent with this finding, experiments that assayed polymerase
      activity on the promoter showed that AZ-27 inhibited transcription and
      replication initiation. The RSV polymerase also can utilize the promoter sequence
      to perform a back-priming reaction. Interestingly, addition of AZ-27 had no
      effect on the addition of up to three nucleotides by back-priming but inhibited
      further extension of the back-primed RNA. These data provide new information
      regarding the mechanism of inhibition by AZ-27. They also suggest that the RSV
      polymerase adopts different conformations to perform its different activities at
      the promoter. IMPORTANCE: Currently, there are no effective antiviral drugs to
      treat RSV infection. The RSV polymerase is an attractive target for drug
      development, but this large enzymatic complex is poorly characterized, hampering
      drug development efforts. AZ-27 is a small-molecule inhibitor previously shown to
      target the RSV large polymerase subunit (C. L. Tiong-Yip et al., Antimicrob
      Agents Chemother, 58:3867-3873, 2014, http://dx.doi.org/10.1128/AAC.02540-14),
      but its inhibitory mechanism was unknown. Understanding this would be valuable
      both for characterizing the polymerase and for further development of inhibitors.
      Here, we show that AZ-27 inhibits an early stage in mRNA transcription, as well
      as genome replication, by inhibiting initiation of RNA synthesis from the
      promoter. However, the compound does not inhibit back priming, another RNA
      synthesis activity of the RSV polymerase. These findings provide insight into the
      different activities of the RSV polymerase and will aid further development of
      antiviral agents against RSV.

PMID- 25995256
TI  - HIV-1 Is Restricted prior to Integration of Viral DNA in Primary Cord-Derived
      Human CD34+ Cells.
AB  - Certain cells have the ability to block retroviral infection at specific stages
      of the viral cycle by the activities of well-characterized factors and
      transcriptional silencing machinery. Infection of murine stem cells (MSCs) by the
      murine leukemia viruses (MLVs) is profoundly blocked postintegration by
      transcriptional silencing. Here, we show that a dominant point of restriction of
      HIV-1 in human CD34+ cells is prior to integration of viral DNA and that HIV-1
      restriction by human CD34+ cells is fundamentally different from MLV restriction
      by mouse cells.

PMID- 25995257
TI  - Caribbean and La Reunion Chikungunya Virus Isolates Differ in Their Capacity To
      Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne arthralgic alphavirus that has
      garnered international attention as an important emerging pathogen since 2005.
      More recently, it invaded the Caribbean islands and the Western Hemisphere.
      Intriguingly, the current CHIKV outbreak in the Caribbean is caused by the Asian
      CHIKV genotype, which differs from the La Reunion LR2006 OPY1 isolate belonging
      to the Indian Ocean lineage. Here, we adopted a systematic and comparative
      approach against LR2006 OPY1 to characterize the pathogenicity of the Caribbean
      CNR20235 isolate and consequential host immune responses in mice. Ex vivo
      infection using primary mouse tail fibroblasts revealed a weaker replication
      efficiency by CNR20235 isolate. In the CHIKV mouse model, CNR20235 infection
      induced an enervated joint pathology characterized by moderate edema and
      swelling, independent of mononuclear cell infiltration. Based on systemic
      cytokine analysis, localized immunophenotyping, and gene expression profiles in
      the popliteal lymph node and inflamed joints, two pathogenic phases were defined
      for CHIKV infection: early acute (2 to 3 days postinfection [dpi]) and late acute
      (6 to 8 dpi). Reduced joint pathology during early acute phase of CNR20235
      infection was associated with a weaker proinflammatory Th1 response and natural
      killer (NK) cell activity. The pathological role of NK cells was further
      demonstrated as depletion of NK cells reduced joint pathology in LR2006 OPY1.
      Taken together, this study provides evidence that the Caribbean CNR20235 isolate
      has an enfeebled replication and induces a less pathogenic response in the
      mammalian host. IMPORTANCE: The introduction of CHIKV in the Americas has
      heightened the risk of large-scale outbreaks due to the close proximity between
      the United States and the Caribbean. The immunopathogenicity of the circulating
      Caribbean CHIKV isolate was explored, where it was demonstrated to exhibit
      reduced infectivity resulting in a weakened joint pathology. Analysis of serum
      cytokine levels, localized immunophenotyping, and gene expression profiles in the
      organs revealed that a limited Th1 response and reduced NK cells activity could
      underlie the reduced pathology in the host. Interestingly, higher asymptomatic
      infections were observed in the Caribbean compared to the La Reunion outbreaks in
      2005 and 2006. This is the first study that showed an association between key
      proinflammatory factors and pathology-mediating leukocytes with a less severe
      pathological outcome in Caribbean CHIKV infection. Given the limited information
      regarding the sequela of Caribbean CHIKV infection, our study is timely and will
      aid the understanding of this increasingly important disease.

PMID- 25995258
TI  - Conservation of G-Protein Epitopes in Respiratory Syncytial Virus (Group A)
      Despite Broad Genetic Diversity: Is Antibody Selection Involved in Virus
      Evolution?
AB  - Worldwide G-glycoprotein phylogeny of human respiratory syncytial virus (hRSV)
      group A sequences revealed diversification in major clades and genotypes over
      more than 50 years of recorded history. Multiple genotypes cocirculated during
      prolonged periods of time, but recent dominance of the GA2 genotype was noticed
      in several studies, and it is highlighted here with sequences from viruses
      circulating recently in Spain and Panama. Reactivity of group A viruses with
      monoclonal antibodies (MAbs) that recognize strain-variable epitopes of the G
      glycoprotein failed to correlate genotype diversification with antibody
      reactivity. Additionally, no clear correlation was found between changes in
      strain-variable epitopes and predicted sites of positive selection, despite both
      traits being associated with the C-terminal third of the G glycoprotein. Hence,
      our data do not lend support to the proposed antibody-driven selection of
      variants as a major determinant of hRSV evolution. Other alternative mechanisms
      are considered to account for the high degree of hRSV G-protein variability.
      IMPORTANCE: An unusual characteristic of the G glycoprotein of human respiratory
      syncytial virus (hRSV) is the accumulation of nonsynonymous (N) changes at higher
      rates than synonymous (S) changes, reaching dN/dS values at certain sites
      predictive of positive selection. Since these sites cluster preferentially in the
      C-terminal third of the G protein, like certain epitopes recognized by murine
      antibodies, it was proposed that immune (antibody) selection might be driving the
      apparent positive selection, analogous to the antigenic drift observed in the
      influenza virus hemagglutinin (HA). However, careful antigenic and genetic
      comparison of the G glycoprotein does not provide evidence of antigenic drift in
      the G molecule, in agreement with recently published data which did not indicate
      antigenic drift in the G protein with human sera. Alternative explanations to the
      immune-driven selection hypothesis are offered to account for the high level of G
      protein genetic diversity highlighted in this study.

PMID- 25995260
TI  - Prolonged Antiretroviral Therapy Preserves HIV-1-Specific CD8 T Cells with Stem
      Cell-Like Properties.
AB  - HIV-1-specific CD8 T cells can influence HIV-1 disease progression during
      untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1
      specific CD8 T cells in individuals treated with suppressive antiretroviral
      therapy remain less well understood. Here we show that a subgroup of HIV-1
      specific CD8 T cells with stem cell-like properties, termed T memory stem cells
      (TSCM cells), is enriched in patients receiving suppressive antiretroviral
      therapy compared with their levels in untreated progressors or controllers. In
      addition, a prolonged duration of antiretroviral therapy was associated with a
      progressive increase in the relative proportions of these stem cell-like HIV-1
      specific CD8 T cells. Interestingly, the proportions of HIV-1-specific CD8 TSCM
      cells and total HIV-1-specific CD8 TSCM cells were associated with the CD4 T cell
      counts during treatment with antiretroviral therapy but not with CD4 T cell
      counts, viral loads, or immune activation parameters in untreated patients,
      including controllers. HIV-1-specific CD8 TSCM cells had increased abilities to
      secrete interleukin-2 in response to viral antigen, while secretion of gamma
      interferon (IFN-gamma) was more limited in comparison to alternative HIV-1
      specific CD8 T cell subsets; however, only proportions of IFN-gamma-secreting HIV
      1-specific CD8 TSCM cells were associated with CD4 T cell counts during
      antiretroviral therapy. Together, these data suggest that HIV-1-specific CD8 TSCM
      cells represent a long-lasting component of the cellular immune response to HIV-1
      that persists in an antigen-independent fashion during antiretroviral therapy but
      seems unable to survive and expand under conditions of ongoing viral replication
      during untreated infection. IMPORTANCE: Memory CD8 T cells that imitate the
      functional properties of stem cells to maintain lifelong cellular immunity have
      been hypothesized for many years, but only recently have such cells, termed T
      memory stem cells (TSCM cells), been physically identified and isolated in
      humans, mice, and nonhuman primates. Here, we investigated whether cellular
      immune responses against HIV-1 include such T memory stem cells. Our data show
      that HIV-1-specific CD8 T memory stem cells are detectable during all stages of
      HIV-1 infection but occur most visibly at times of prolonged viral antigen
      suppression by antiretroviral combination therapy. These cells may therefore be
      particularly relevant for designing antiviral immune defense strategies against
      the residual reservoir of HIV-1-infected cells that persists despite treatment
      and leads to viral rebound upon treatment discontinuation.

PMID- 25995261
TI  - A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency
      in Strand Transfer Causes a Loss of Viral Replication.
AB  - The process of reverse transcription (RTN) in retroviruses is essential to the
      viral life cycle. This key process is catalyzed exclusively by the viral reverse
      transcriptase (RT) that copies the viral RNA into DNA by its DNA polymerase
      activity, while concomitantly removing the original RNA template by its RNase H
      activity. During RTN, the combination between DNA synthesis and RNA hydrolysis
      leads to strand transfers (or template switches) that are critical for the
      completion of RTN. The balance between these RT-driven activities was considered
      to be the sole reason for strand transfers. Nevertheless, we show here that a
      specific mutation in HIV-1 RT (L92P) that does not affect the DNA polymerase and
      RNase H activities abolishes strand transfer. There is also a good correlation
      between this complete loss of the RT's strand transfer to the loss of the DNA
      clamp activity of the RT, discovered recently by us. This finding indicates a
      mechanistic linkage between these two functions and that they are both direct and
      unique functions of the RT (apart from DNA synthesis and RNA degradation).
      Furthermore, when the RT's L92P mutant was introduced into an infectious HIV-1
      clone, it lost viral replication, due to inefficient intracellular strand
      transfers during RTN, thus supporting the in vitro data. As far as we know, this
      is the first report on RT mutants that specifically and directly impair RT
      associated strand transfers. Therefore, targeting residue Leu92 may be helpful in
      selectively blocking this RT activity and consequently HIV-1 infectivity and
      pathogenesis. IMPORTANCE: Reverse transcription in retroviruses is essential for
      the viral life cycle. This multistep process is catalyzed by viral reverse
      transcriptase, which copies the viral RNA into DNA by its DNA polymerase activity
      (while concomitantly removing the RNA template by its RNase H activity). The
      combination and balance between synthesis and hydrolysis lead to strand transfers
      that are critical for reverse transcription completion. We show here for the
      first time that a single mutation in HIV-1 reverse transcriptase (L92P)
      selectively abolishes strand transfers without affecting the enzyme's DNA
      polymerase and RNase H functions. When this mutation was introduced into an
      infectious HIV-1 clone, viral replication was lost due to an impaired
      intracellular strand transfer, thus supporting the in vitro data. Therefore,
      finding novel drugs that target HIV-1 reverse transcriptase Leu92 may be
      beneficial for developing new potent and selective inhibitors of retroviral
      reverse transcription that will obstruct HIV-1 infectivity.

PMID- 25995259
TI  - Inhibitory Effect of Individual or Combinations of Broadly Neutralizing
      Antibodies and Antiviral Reagents against Cell-Free and Cell-to-Cell HIV-1
      Transmission.
AB  - To date, most therapeutic and vaccine candidates for human immunodeficiency virus
      type 1 (HIV-1) are evaluated preclinically for efficacy against cell-free viral
      challenges. However, cell-associated HIV-1 is suggested to be a major contributor
      to sexual transmission by mucosal routes. To determine if neutralizing antibodies
      or inhibitors block cell-free and cell-associated virus transmission of diverse
      HIV-1 strains with different efficiencies, we tested 12 different antibodies and
      five inhibitors against four green fluorescent protein (GFP)-labeled HIV-1
      envelope (Env) variants from transmitted/founder (T/F) or chronic infection
      isolates. We evaluated antibody/inhibitor-mediated virus neutralization using
      either TZM-bl target cells, in which infectivity was determined by virus-driven
      luciferase expression, or A3R5 lymphoblastoid target cells, in which infectivity
      was evaluated by GFP expression. In both the TZM-bl and A3R5 assays, cell-free
      virus or infected CD4+ lymphocytes were used as targets for neutralization. We
      further hypothesized that the combined use of specific neutralizing antibodies
      targeting HIV-1 Env would more effectively prevent cell-associated virus
      transmission than the use of individual antibodies. The tested antibody
      combinations included two gp120-directed antibodies, VRC01 and PG9, or VRC01 with
      the gp41-directed antibody 10E8. Our results demonstrated that cell-associated
      virus was less sensitive to neutralizing antibodies and inhibitors, particularly
      using the A3R5 neutralization assay, and the potencies of these neutralizing
      agents differed among Env variants. A combination of different neutralizing
      antibodies that target specific sites on gp120 led to a significant reduction in
      cell-associated virus transmission. These assays will help identify ideal
      combinations of broadly neutralizing antibodies to use for passive preventive
      antibody administration and further characterize targets for the most effective
      neutralizing antibodies/inhibitors. IMPORTANCE: Prevention of the transmission of
      human immunodeficiency virus type 1 (HIV-1) remains a prominent goal of HIV
      research. The relative contribution of HIV-1 within an infected cell versus cell
      free HIV-1 to virus transmission remains debated. It has been suggested that cell
      associated virus is more efficient at transmitting HIV-1 and more difficult to
      neutralize than cell-free virus. Several broadly neutralizing antibodies and
      retroviral inhibitors are currently being studied as potential therapies against
      HIV-1 transmission. The present study demonstrates a decrease in neutralizing
      antibody and inhibitor efficiencies against cell-associated compared to cell-free
      HIV-1 transmission among different strains of HIV-1. We also observed a
      significant reduction in virus transmission using a combination of two different
      neutralizing antibodies that target specific sites on the outermost region of HIV
      1, the virus envelope. Therefore, our findings support the use of antibody
      combinations against both cell-free and cell-associated virus in future candidate
      therapy regimens.

PMID- 25995262
TI  - Herpes Simplex Virus 1 Recruits CD98 Heavy Chain and beta1 Integrin to the
      Nuclear Membrane for Viral De-Envelopment.
AB  - Herpesviruses have evolved a unique mechanism for nucleocytoplasmic transport of
      nascent nucleocapsids: the nucleocapsids bud through the inner nuclear membrane
      (INM; primary envelopment), and the enveloped nucleocapsids then fuse with the
      outer nuclear membrane (de-envelopment). Little is known about the molecular
      mechanism of herpesviral de-envelopment. We show here that the knockdown of both
      CD98 heavy chain (CD98hc) and its binding partner beta1 integrin induced
      membranous structures containing enveloped herpes simplex virus 1 (HSV-1) virions
      that are invaginations of the INM into the nucleoplasm and induced aberrant
      accumulation of enveloped virions in the perinuclear space and in the
      invagination structures. These effects were similar to those of the previously
      reported mutation(s) in HSV-1 proteins gB, gH, UL31, and/or Us3, which were shown
      here to form a complex(es) with CD98hc in HSV-1-infected cells. These results
      suggested that cellular proteins CD98hc and beta1 integrin synergistically or
      independently regulated HSV-1 de-envelopment, probably by interacting directly
      and/or indirectly with these HSV-1 proteins. IMPORTANCE: Certain cellular and
      viral macromolecular complexes, such as Drosophila large ribonucleoprotein
      complexes and herpesvirus nucleocapsids, utilize a unique vesicle-mediated
      nucleocytoplasmic transport: the complexes acquire primary envelopes by budding
      through the inner nuclear membrane into the space between the inner and outer
      nuclear membranes (primary envelopment), and the enveloped complexes then fuse
      with the outer nuclear membrane to release de-enveloped complexes into the
      cytoplasm (de-envelopment). However, there is a lack of information on the
      molecular mechanism of de-envelopment fusion. We report here that HSV-1 recruited
      cellular fusion regulatory proteins CD98hc and beta1 integrin to the nuclear
      membrane for viral de-envelopment fusion. This is the first report of cellular
      proteins required for efficient de-envelopment of macromolecular complexes during
      their nuclear egress.

PMID- 25995263
TI  - Phosphatidylinositol-(4,5)-Bisphosphate Acyl Chains Differentiate Membrane
      Binding of HIV-1 Gag from That of the Phospholipase Cdelta1 Pleckstrin Homology
      Domain.
AB  - HIV-1 Gag, which drives virion assembly, interacts with a plasma membrane (PM)
      specific phosphoinositide, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2].
      While cellular acidic phospholipid-binding proteins/domains, such as the
      PI(4,5)P2-specific pleckstrin homology domain of phospholipase Cdelta1
      (PHPLCdelta1), mediate headgroup-specific interactions with corresponding
      phospholipids, the exact nature of the Gag-PI(4,5)P2 interaction remains
      undetermined. In this study, we used giant unilamellar vesicles (GUVs) to examine
      how PI(4,5)P2 with unsaturated or saturated acyl chains affect membrane binding
      of PHPLCdelta1 and Gag. Both unsaturated dioleoyl-PI(4,5)P2 [DO-PI(4,5)P2] and
      saturated dipalmitoyl-PI(4,5)P2 [DP-PI(4,5)P2] successfully recruited PHPLCdelta1
      to membranes of single-phase GUVs. In contrast, DO-PI(4,5)P2 but not DP-PI(4,5)P2
      recruited Gag to GUVs, indicating that PI(4,5)P2 acyl chains contribute to stable
      membrane binding of Gag. GUVs containing PI(4,5)P2, cholesterol, and dipalmitoyl
      phosphatidylserine separated into two coexisting phases: one was a liquid phase,
      and the other appeared to be a phosphatidylserine-enriched gel phase. In these
      vesicles, the liquid phase recruited PHPLCdelta1 regardless of PI(4,5)P2 acyl
      chains. Likewise, Gag bound to the liquid phase when PI(4,5)P2 had DO-acyl
      chains. DP-PI(4,5)P2-containing GUVs showed no detectable Gag binding to the
      liquid phase. Unexpectedly, however, DP-PI(4,5)P2 still promoted recruitment of
      Gag, but not PHPLCdelta1, to the dipalmitoyl-phosphatidylserine-enriched gel
      phase of these GUVs. Altogether, these results revealed different roles for
      PI(4,5)P2 acyl chains in membrane binding of two PI(4,5)P2-binding proteins, Gag
      and PHPLCdelta1. Notably, we observed that nonmyristylated Gag retains the
      preference for PI(4,5)P2 containing an unsaturated acyl chain over DP-PI(4,5)P2,
      suggesting that Gag sensitivity to PI(4,5)P2 acyl chain saturation is determined
      directly by the matrix-PI(4,5)P2 interaction, rather than indirectly by a
      myristate-dependent mechanism. IMPORTANCE: Binding of HIV-1 Gag to the plasma
      membrane is promoted by its interaction with a plasma membrane-localized
      phospholipid, PI(4,5)P2. Many cellular proteins are also recruited to the plasma
      membrane via PI(4,5)P2-interacting domains represented by PHPLCdelta1. However,
      differences and/or similarities between these host proteins and viral Gag protein
      in the nature of their PI(4,5)P2 interactions, especially in the context of
      membrane binding, remain to be determined. Using a novel giant unilamellar
      vesicle-based system, we found that PI(4,5)P2 with an unsaturated acyl chain
      recruited PHPLCdelta1 and Gag similarly, whereas PI(4,5)P2 with saturated acyl
      chains either recruited PHPLCdelta1 but not Gag or sorted these proteins to
      different phases of vesicles. To our knowledge, this is the first study to show
      that PI(4,5)P2 acyl chains differentially modulate membrane binding of PI(4,5)P2
      binding proteins. Since Gag membrane binding is essential for progeny virion
      production, the PI(4,5)P2 acyl chain property may serve as a potential target for
      anti-HIV therapeutic strategies.

PMID- 25995264
TI  - Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31
      Represent a Single L1 Serotype.
AB  - We investigated naturally occurring variation within the major (L1) and minor
      (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31)
      to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs)
      representing the three HPV31 variant lineages, variant lineages A, B, and C,
      exhibited comparable particle-to-infectivity ratios and morphologies. Lineage
      specific L1L2 PsVs demonstrated subtle differences in susceptibility to
      neutralization by antibodies elicited following vaccination or preclinical L1
      virus-like particle (VLP) immunization or by monoclonal antibodies; however,
      these differences were generally of a low magnitude. These data indicate that the
      diagnostic lineage-specific single nucleotide polymorphisms within the HPV31
      capsid genes have a limited effect on L1 antibody-mediated neutralization and
      that the three HPV31 variant lineages belong to a single L1 serotype. These data
      contribute to our understanding of HPV L1 variant antigenicity. IMPORTANCE: The
      virus coat (capsid) of the human papillomavirus contains major (L1) and minor
      (L2) capsid proteins. These proteins facilitate host cell attachment and viral
      infectivity and are the targets for antibodies which interfere with these events.
      In this study, we investigated the impact of naturally occurring variation within
      these proteins upon susceptibility to viral neutralization by antibodies induced
      by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit
      similar susceptibility to antibody-mediated neutralization and that for the
      purposes of L1 VLP-based vaccines, these variant lineages represent a single
      serotype.

PMID- 25995266
TI  - Time to abandon the 'vintage' laryngeal mask airway and adopt second-generation
      supraglottic airway devices as first choice.

PMID- 25995265
TI  - Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a
      Model for Vaccine Evaluation.
AB  - Influenza infection causes severe disease and death in humans. In traditional
      vaccine research and development, a single high-dose virus challenge of animals
      is used to evaluate vaccine efficacy. This type of challenge model may have
      limitations. In the present study, we developed a novel challenge model by
      infecting mice repeatedly in short intervals with low doses of influenza A virus.
      Our results show that compared to a single high-dose infection, mice that
      received repeated low-dose challenges showed earlier morbidity and mortality and
      more severe disease. They developed higher vial loads, more severe lung
      pathology, and greater inflammatory responses and generated only limited
      influenza A virus-specific B and T cell responses. A commercial trivalent
      influenza vaccine protected mice against a single high and lethal dose of
      influenza A virus but was ineffective against repeated low-dose virus challenges.
      Overall, our data show that the repeated low-dose influenza A virus infection
      mouse model is more stringent and may thus be more suitable to select for highly
      efficacious influenza vaccines. IMPORTANCE: Influenza epidemics and pandemics
      pose serious threats to public health. Animal models are crucial for evaluating
      the efficacy of influenza vaccines. Traditional models based on a single high
      dose virus challenge may have limitations. Here, we describe a new mouse model
      based on repeated low-dose influenza A virus challenges given within a short
      period. Repeated low-dose challenges caused more severe disease in mice,
      associated with higher viral loads and increased lung inflammation and reduced
      influenza A virus-specific B and T cell responses. A commercial influenza vaccine
      that was shown to protect mice from high-dose challenge was ineffective against
      repeated low-dose challenges. Overall, our results show that the low-dose
      repeated-challenge model is more stringent and may therefore be better suited for
      preclinical vaccine efficacy studies.

PMID- 25995267
TI  - Homeostatic 'bystander' proliferation of human peripheral blood B cells in
      response to polyclonal T-cell stimulation in vitro.
AB  - The mechanisms of maintenance of adequate numbers of B lymphocytes and of
      protective levels of immunoglobulins in the absence of antigenic (re)stimulation
      remain not fully understood. Meanwhile, our results presented here show that both
      peripheral blood naive and memory B cells can be activated strongly and non
      specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3-
      or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of
      healthy people. This polyclonal, bystander activation of the B cells includes
      multiple divisions of most of them (assessed here by the flow cytometric
      technique of dividing cell tracking) and significant antibody [immunoglobulin M
      (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends
      on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and
      on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is
      correlated with the levels of these Th-derived molecules, while it does not
      involve the ligation of the BCR/CD19 complex. We suggest that the effect might
      reflect the situation occurring in vivo as the homeostatic proliferation of
      otherwise non-stimulated, peripheral B lymphocytes, providing an always ready
      pool for efficient antibody production to any new (or cognate) antigen challenge.

PMID- 25995268
TI  - Quantification of GC-biased gene conversion in the human genome.
AB  - Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact
      on the evolution of mammalian genomes. However, a detailed quantification of the
      process is still lacking. The strength of gBGC can be measured from the analysis
      of derived allele frequency spectra (DAF), but this approach is sensitive to a
      number of confounding factors. In particular, we show by simulations that the
      inference is pervasively affected by polymorphism polarization errors and by
      spatial heterogeneity in gBGC strength. We propose a new general method to
      quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial
      heterogeneity into account, and jointly estimating mutation bias. Applying it to
      human polymorphism data from the 1000 Genomes Project, we show that the strength
      of gBGC does not differ between hypermutable CpG sites and non-CpG sites,
      suggesting that in humans gBGC is not caused by the base-excision repair
      machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area.
      However, given that recombination occurs primarily within recombination hotspots,
      1%-2% of the human genome is subject to strong gBGC. On average, gBGC is stronger
      in African than in non-African populations, reflecting differences in effective
      population sizes. However, due to more heterogeneous recombination landscapes,
      the fraction of the genome affected by strong gBGC is larger in non-African than
      in African populations. Given that the location of recombination hotspots evolves
      very rapidly, our analysis predicts that, in the long term, a large fraction of
      the genome is affected by short episodes of strong gBGC. 

PMID- 25995269
TI  - Retrotransposition creates sloping shores: a graded influence of hypomethylated
      CpG islands on flanking CpG sites.
AB  - Long interspersed elements (LINEs), through both self-mobilization and trans
      mobilization of short interspersed elements and processed pseudogenes, have made
      an indelible impact on the structure and function of the human genome. One
      consequence is the creation of new CpG islands (CGIs). In fact, more than half of
      all CGIs in the genome are associated with repetitive DNA, three-quarters of
      which are derived from retrotransposons. However, little is known about the
      epigenetic impact of newly inserted CGIs. We utilized a transgenic LINE-1 mouse
      model and tracked DNA methylation dynamics of individual germline insertions
      during mouse development. The retrotransposed GFP marker sequence, a strong CGI,
      is hypomethylated in male germ cells but hypermethylated in somatic tissues,
      regardless of genomic location. The GFP marker is similarly methylated when
      delivered into the genome via the Sleeping Beauty DNA transposon, suggesting that
      the observed methylation pattern may be independent of the mode of insertion.
      Comparative analyses between insertion- and non-insertion-containing alleles
      further reveal a graded influence of the retrotransposed CGI on flanking CpG
      sites, a phenomenon that we described as "sloping shores." Computational analyses
      of human and mouse methylomic data at single-base resolution confirm that sloping
      shores are universal for hypomethylated CGIs in sperm and somatic tissues.
      Additionally, the slope of a hypomethylated CGI can be affected by closely
      positioned CGI neighbors. Finally, by tracing sloping shore dynamics through
      embryonic and germ cell reprogramming, we found evidence of bookmarking, a
      mechanism that likely determines which CGIs will be eventually hyper- or
      hypomethylated. 

PMID- 25995271
TI  - NFAT5 Is Up-Regulated by Hypoxia: Possible Implications in Preeclampsia and
      Intrauterine Growth Restriction.
AB  - During gestation, low oxygen environment is a major determinant of early
      placentation process, while persistent placental hypoxia leads to pregnancy
      related complications such as preeclampsia (PE) and intrauterine growth
      restriction (IUGR). PE affects 5%-8% of all pregnancies worldwide and is a cause
      of maternal and fetal morbidity and mortality. During placental development,
      persistent hypoxia due to poor trophoblast invasion and reduced uteroplacental
      perfusion leads to maternal endothelial dysfunction and clinical manifestation of
      PE. Here we hypothesized that nuclear factor of activated T cells-5 (NFAT5), a
      well-known osmosensitive renal factor and recently characterized hypoxia
      inducible protein, is also activated in vivo in placentas of PE and IUGR
      complications as well as in the in vitro model of trophoblast hypoxia. In JAR
      cells, low oxygen tension (1% O2) induced NFAT5 mRNA and increased its nuclear
      abundance, peaking at 16 h. This increase did not occur in parallel with the
      earlier HIF1A induction. Real-time PCR and Western blot analysis confirmed up
      regulation of NFAT5 mRNA and NFAT5 nuclear content in human preeclamptic
      placentas and in rabbit placentas of an experimentally induced IUGR model, as
      compared with the control groups. In vitro lambda protein phosphatase (lambda
      PPase) treatment revealed that increased abundance of NFAT5 protein in nuclei of
      either JAR cells (16 h of hypoxia) or PE and IUGR placentas is at least partially
      due to NFAT5 phosphorylation. NFAT5 downstream targets aldose reductase (AR) and
      sodium-myo-inositol cotransporter (SMIT; official symbol SLC5A3) were not
      significantly up-regulated either in JAR cells exposed to hypoxia or in placentas
      of PE- and IUGR-complicated pregnancies, suggesting that hypoxia-dependent
      activation of NFAT5 serves as a separate function to its tonicity-dependent
      stimulation. In conclusion, we propose that NFAT5 may serve as a novel marker of
      placental hypoxia and ischemia independently of HIF1A. 

PMID- 25995270
TI  - Topologically associating domains and their long-range contacts are established
      during early G1 coincident with the establishment of the replication-timing
      program.
AB  - Mammalian genomes are partitioned into domains that replicate in a defined
      temporal order. These domains can replicate at similar times in all cell types
      (constitutive) or at cell type-specific times (developmental). Genome-wide
      chromatin conformation capture (Hi-C) has revealed sub-megabase topologically
      associating domains (TADs), which are the structural counterparts of replication
      domains. Hi-C also segregates inter-TAD contacts into defined 3D spatial
      compartments that align precisely to genome-wide replication timing profiles.
      Determinants of the replication-timing program are re-established during early G1
      phase of each cell cycle and lost in G2 phase, but it is not known when TAD
      structure and inter-TAD contacts are re-established after their elimination
      during mitosis. Here, we use multiplexed 4C-seq to study dynamic changes in
      chromatin organization during early G1. We find that both establishment of TADs
      and their compartmentalization occur during early G1, within the same time frame
      as establishment of the replication-timing program. Once established, this 3D
      organization is preserved either after withdrawal into quiescence or for the
      remainder of interphase including G2 phase, implying 3D structure is not
      sufficient to maintain replication timing. Finally, we find that developmental
      domains are less well compartmentalized than constitutive domains and display
      chromatin properties that distinguish them from early and late constitutive
      domains. Overall, this study uncovers a strong connection between chromatin re
      organization during G1, establishment of replication timing, and its
      developmental control. 

PMID- 25995272
TI  - Augmentation of Metastin/Kisspeptin mRNA Expression by the Proestrous Luteinizing
      Hormone Surge in Granulosa Cells of Rats: Implications for Luteinization.
AB  - Variations in mRNA levels and sources of metastin/kisspeptin, neurokinin B (NKB),
      dynorphin, and kisspeptin receptor GPR54 were examined in the ovaries of cycling
      rats. Kisspeptin and dynorphin mRNAs dramatically increased at 2000 h of the
      proestrous day. NKB mRNA also increased, but the peak was delayed by 6 h. GPR54
      mRNA declined inversely with kisspeptin. Whole-ovary expressions of kisspeptin
      and dynorphin mRNAs, but not of NKB mRNA, were augmented by the administration of
      human chorionic gonadotropin (hCG). By means of laser-capture microdissection,
      kisspeptin mRNA was shown mostly in follicles at 2000 h of proestrus, whereas NKB
      and dynorphin were expressed mainly in interstitial tissues. GPR54 mRNA was
      detected equally in follicles, corpora lutea, and interstitial tissues. The hCG
      stimulated the follicular expression of kisspeptin and interstitial tissue
      expression of dynorphin mRNA. In primary cultures of granulosa cells prepared
      from equine chorionic gonadotropin-pretreated immature rats, hCG stimulated the
      expression of kisspeptin, dynorphin, and NKB mRNAs. Distortion of the corpus
      luteum and surrounding tissue borders was sometimes seen after intra-ovarian
      bursa administration of kisspeptin antagonist p234 for 3 days from proestrus.
      Progesterone production stimulated by hCG in granulosa cell culture was
      suppressed by p234. These data demonstrate that significant amounts of kisspeptin
      are synthesized in granulosa cells and dynorphin in interstitial tissues, in
      response to the proestrous luteinizing hormone surge, whereas granulosa cells
      also contain dynorphin and NKB, suggesting at least a role for kisspeptin in the
      luteinization of granulosa cells. 

PMID- 25995274
TI  - Questioning the significance of the non-identity problem in applied ethics.
AB  - Authors such as Tony Hope and Julian Savulescu appeal to Derek Parfit's non
      identity problem in relation to particular questions in applied ethics, and
      particularly in reproductive ethics. They argue that the non-identity problem
      shows that an individual cannot be harmed by being brought into existence, and
      therefore, we cannot say that the individual is harmed if, for example, we select
      an embryo in order to have a deaf child. Thus, they argue that an appeal to the
      non-identity problem blocks (or significantly reduces the force of) objections in
      a number of cases. I argue that these discussions often give the impression that
      this is a clear conclusion, shared by most philosophers, and largely beyond
      dispute. This is particularly significant because these discussions are often in
      journals or books with an interdisciplinary readership. My concern is that they
      give the impression of stating: 'philosophers have studied this issue, and this
      is the conclusion they have reached. Now I will emphasise the implications for
      medical ethics'. I argue that, far from being the consensus view, the view
      presented by Hope and Savulescu is rejected by many, including Parfit himself. 

PMID- 25995273
TI  - Tissue-Specific Glycosylation at the Glycopeptide Level.
AB  - This manuscript describes the enrichment and mass spectrometric analysis of
      intact glycopeptides from mouse liver, which yielded site-specific N- and O
      glycosylation data for ~ 130 proteins. Incorporation of different sialic acid
      variants in both N- and O-linked glycans was observed, and the importance of
      using both collisional activation and electron transfer dissociation for
      glycopeptide analysis was illustrated. The N-glycan structures of predicted
      lysosomal, endoplasmic reticulum (ER), secreted and transmembrane proteins were
      compared. The data suggest that protein N-glycosylation differs depending on
      cellular location. The glycosylation patterns of several mouse liver and mouse
      brain glycopeptides were compared. Tissue-specific differences in glycosylation
      were observed between sites within the same protein: Some sites displayed a
      similar spectrum of glycan structures in both tissues, whereas for others no
      overlap was observed. We present comparative brain/liver glycosylation data on 50
      N-glycosylation sites from 34 proteins and 13 O-glycosylation sites from seven
      proteins.

PMID- 25995275
TI  - High Preformed Vitamin A Intake during Pregnancy Prevents Embryonic Accumulation
      of Intact beta-Carotene from the Maternal Circulation in Mice.
AB  - BACKGROUND: The vitamin A precursor beta-carotene (BC) promotes mammalian
      embryonic development by serving as a source of retinoids (vitamin A derivatives)
      to the developing tissues. In the Western world, increased consumption of dietary
      supplements, including vitamin A and BC, is common; however, the consequences of
      maternal high preformed vitamin A intake on embryonic uptake and metabolism of BC
      are poorly understood. OBJECTIVE: This study investigated vitamin A and BC
      metabolism in developing mouse tissues after a single BC administration to
      pregnant wild-type (WT) mice fed purified diets with different vitamin A
      concentrations. METHODS: WT dams fed a sufficient vitamin A (VA-S; 4.2 MUg of
      retinol/g of diet), high vitamin A (VA-H; 33 MUg of retinol/g of diet), or excess
      vitamin A (VA-E; 66 MUg of retinol/g of diet) diet throughout gestation were
      intraperitoneally injected with BC or vehicle at 13.5 d postcoitum (dpc). At 14.5
      dpc, retinoid and BC concentrations in maternal serum and liver, placenta, and
      embryo were quantified by HPLC; expressions of genes controlling retinoid and BC
      homeostasis were analyzed by quantitative polymerase chain reaction. Maternal
      lipoprotein BC concentrations were analyzed by density gradient
      ultracentrifugation followed by HPLC. RESULTS: Intact BC was undetectable only in
      embryos from VA-E + BC dams. Relative to the VA-S + vehicle group, placentas from
      VA-S + BC dams showed 39% downregulation of LDL-receptor-related protein 1 (Lrp1
      ); 35% downregulation of VLDL receptor (Vldlr); 56% reduced mRNA expression of
      beta-carotene 15,15'-oxygenase (Bco1); and 80% upregulation of beta-carotene
      9',10'-oxygenase (Bco2). Placental cytochrome P450, family 26, subfamily A,
      polypeptide 1 (Cyp26A1) was upregulated 2-fold in the VA-E group compared with
      the VA-S group, regardless of maternal treatment. CONCLUSIONS: In mice, transfer
      of intact BC to the embryo is attenuated by high tissue vitamin A concentrations.
      Maternal vitamin A intake and BC availability activate a placental
      transcriptional response to protect the embryo from retinoid and carotenoid
      excess.

PMID- 25995276
TI  - Malawian Mothers Consider Lipid-Based Nutrient Supplements Acceptable for
      Children throughout a 1-Year Intervention, but Deviation from User
      Recommendations Is Common.
AB  - BACKGROUND: Lipid-based nutrient supplements (LNSs) offer a vehicle to improve
      children's diets in low-income countries where complementary foods are typically
      deficient in essential nutrients. Sustained acceptability by the intended users
      is essential for achieving growth-promoting effects. OBJECTIVE: We aimed to
      determine the sustained acceptability of LNSs among 6- to 18-mo-old children in
      Malawi. METHODS: In the context of a trial testing the growth-promoting effect of
      different formulations and doses of LNSs, we delivered LNSs to the homes of the
      children biweekly according to the randomization protocol. We defined
      acceptability to include adherence to feeding recommendations and mothers'
      experiences of feeding LNSs to their child. We conducted brief interviews each
      week with the mothers. At 2 time points we conducted knowledge, attitudes, and
      practices (KAP) interviews. In addition, we conducted repeated in-depth
      interviews with a subset of mothers. RESULTS: Of the 1612 children who received
      the LNS intervention, we analyzed adherence data from 1478 (91.7%) children and
      KAP data at 2 time points (child's age of 12 and 18 mo) from 839 (52.1%) of the
      children. The mean +/- SD overall adherence (proportion of days when the study
      child reportedly consumed LNSs considering only those weeks when the supplement
      had been successfully delivered to the home) was 92.4 +/- 9.6%, and there was no
      difference between children receiving milk-containing or milk-free LNSs. There
      was also no increasing or decreasing trend over time in any of the groups.
      Sharing and deviation from other feeding recommendations were common. Maternal
      experiences were mostly very positive. CONCLUSIONS: The acceptability of LNS
      products was good and was sustained for 12 mo in this rural Malawian population.
      However, sharing of the products with family members and deviation from other
      feeding recommendations were frequent, which means that individually targeted
      children were likely to receive less than the intended dose of the LNS. This
      trial was registered at clinicaltrials.gov as NCT00945698.

PMID- 25995277
TI  - Household Food Insecurity Is a Stronger Marker of Adequacy of Nutrient Intakes
      among Canadian Compared to American Youth and Adults.
AB  - BACKGROUND: The most recent statistics indicate that the prevalence of food
      insecurity in the United States is double that in Canada, but the extent to which
      the nutrition implications of this problem differ between the countries is not
      known. OBJECTIVE: This study was undertaken to compare adequacy of nutrient
      intakes in relation to household food insecurity among youth and adults in Canada
      and the United States. METHODS: Data from comparable nationally representative
      surveys, the 2004 Canadian Community Health Survey and the 2003-2006 NHANES, were
      used to estimate prevalences of inadequate intakes of vitamins A and C, folate,
      calcium, magnesium, and zinc among youth and adults in food-secure and food
      insecure households. Potential differences in the composition of the populations
      between the 2 countries were addressed by using standardization, and analyses
      also accounted for participation in food and nutrition assistance programs in the
      United States. RESULTS: Larger gaps in the prevalences of inadequate intakes
      between those in food-secure and food-insecure households were observed in Canada
      than in the United States for calcium and magnesium. For calcium, the prevalences
      of inadequate intakes among those in food-secure and food-insecure households in
      Canada were 50% and 66%, respectively, compared with 50% and 51%, respectively,
      in the United States. For magnesium, the prevalences of inadequate intakes in
      Canada were 39% and 60% among those in food-secure and food-insecure households,
      respectively, compared with 60% and 61%, respectively, in the United States.
      These findings were largely unchanged after we accounted for participation in
      food and nutrition assistance programs in the United States. CONCLUSIONS: This
      study suggests that household food insecurity is a stronger marker of nutritional
      vulnerability in Canada than in the United States. The results highlight the need
      for research to elucidate the effects of domestic policies affecting factors such
      as food prices and fortification on the nutritional manifestations of food
      insecurity.

PMID- 25995278
TI  - Vitamin B-12 Status Differs among Pregnant, Lactating, and Control Women with
      Equivalent Nutrient Intakes.
AB  - BACKGROUND: Limited data are available from controlled studies on biomarkers of
      maternal vitamin B-12 status. OBJECTIVE: We sought to quantify the effects of
      pregnancy and lactation on the vitamin B-12 status response to a known and highly
      controlled vitamin B-12 intake. METHODS: As part of a 10-12 wk feeding trial,
      pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and
      control (nonpregnant, nonlactating; n = 21) women consumed vitamin B-12 amounts
      of ~8.6 MUg/d [mixed diet (~6 MUg/d) plus a prenatal multivitamin supplement (2.6
      MUg/d)]. Serum vitamin B-12, holotranscobalamin (bioactive form of vitamin B-12),
      methylmalonic acid (MMA), and homocysteine were measured at baseline and study
      end. RESULTS: All participants achieved adequate vitamin B-12 status in response
      to the study dose. Compared with control women, pregnant women had lower serum
      vitamin B-12 (-21%; P = 0.02) at study-end, whereas lactating women had higher (P
      = 0.04) serum vitamin B-12 throughout the study (+26% at study-end). Consumption
      of the study vitamin B-12 dose increased serum holotranscobalamin in all
      reproductive groups (+16-42%; P <= 0.009). At study-end, pregnant (vs. control)
      women had a higher holotranscobalamin-to-vitamin B-12 ratio (P = 0.04) with ~30%
      (vs. 20%) of total vitamin B-12 in the bioactive form. Serum MMA increased during
      pregnancy (+50%; P < 0.001) but did not differ by reproductive state at study
      end. Serum homocysteine increased in pregnant women (+15%; P = 0.009) but
      decreased in control and lactating women (-16-17%; P < 0.001). Despite these
      changes, pregnant women had ~20% lower serum homocysteine than the other 2 groups
      at study-end (P <= 0.02). CONCLUSION: Pregnancy and lactation alter vitamin B-12
      status in a manner consistent with enhanced vitamin B-12 supply to the child.
      Consumption of the study vitamin B-12 dose (~3 times the RDA) increased the
      bioactive form of vitamin B-12, suggesting that women in these reproductive
      states may benefit from vitamin B-12 intakes exceeding current recommendations.
      This trial was registered at clinicaltrials.gov as NCT01127022.

PMID- 25995279
TI  - Confirmatory Factor Analysis Compared with Principal Component Analysis to Derive
      Dietary Patterns: A Longitudinal Study in Adult Women.
AB  - BACKGROUND: Principal component analysis (PCA) has been used extensively to
      derive dietary patterns. We proposed to use confirmatory factor analysis (CFA) in
      the same context as PCA--as a one-step approach--to derive dietary patterns.
      OBJECTIVES: The first aim of this study was methodologic and was to compare
      dietary patterns derived with the use of PCA and CFA, used as equivalent one-step
      approaches. The second aim of this study was to study these patterns in
      association with individual characteristics and new adult-onset asthma. METHODS:
      We included 30,589 French women from the E3N (epidemiologic prospective cohort
      study of women from the MGEN national insurance plan) with 1177 reported cases of
      adult-onset asthma between 1993 and 2005. PCA and CFA were used in the same
      context, on 27 food groups, to derive dietary patterns. Associations between
      dietary patterns and adult-onset asthma were assessed by Cox proportional hazards
      models. RESULTS: Whether we used PCA or CFA, 3 similar factors were found and
      labeled "Prudent," "Western," and "Aperitif." Correlations between patterns
      derived with the use of PCA and CFA were high. For the "Prudent" and "Aperitif"
      patterns, we observed comparable patterns in terms of associations with food
      groups, individual characteristics, and the onset of asthma. For the "Western"
      patterns, the one derived with the use of CFA was more related to an unhealthy
      diet than the one derived with the use of PCA, with higher correlations with the
      food groups "processed meat" (0.73 vs. 0.51) and "dough and pastry" (0.63 vs.
      0.40), and negative associations with physical activity and with having parents
      who were farmers. Regarding associations with adult-onset asthma, a significant
      positive association was observed for the "Western" pattern derived with the use
      of CFA [multivariate RR for highest vs. lowest quintile: 1.30 (1.02, 1.67), P
      trend: 0.03], whereas no association was reported when using PCA [RR: 1.14 (0.89,
      1.47), P-trend: 0.40]. CONCLUSION: Although quite similar dietary patterns were
      derived with the use of PCA and CFA, this study supports the alternative use of
      CFA to PCA for the identification of dietary patterns in epidemiologic studies.

PMID- 25995280
TI  - Lactation Consultant Support from Late Pregnancy with an Educational Intervention
      at 4 Months of Age Delays the Introduction of Complementary Foods in a Randomized
      Controlled Trial.
AB  - BACKGROUND: Although the WHO recommends that complementary feeding in infants
      should begin at 6 mo of age, it often begins before this in developed countries.
      OBJECTIVE: Our objective was to determine whether lactation consultant (LC)
      support, with educational resources given at 4-mo postpartum, can delay the
      introduction of complementary foods until around 6 mo of age. METHODS: A total of
      802 mother-infant pairs were recruited from the single maternity hospital serving
      Dunedin, New Zealand (59% response rate) and randomly assigned to the following:
      1) usual care (control group); 2) infant sleep education intervention (Sleep); 3)
      food, activity, and breastfeeding intervention (FAB); or 4) combination (both)
      intervention (Combo). Certified LCs delivered 3 intervention sessions (late
      pregnancy and 1-wk and 4-mo postpartum). The 4-mo contact used educational
      resources focused on developmental readiness for complementary foods. Age when
      complementary foods were introduced was obtained from repeated interviews
      (monthly from 3- to 27-wk postpartum). RESULTS: A total of 49.5% and 87.2% of
      infants received complementary foods before 5 and 6 mo of age, respectively.
      There was evidence of group differences in the number of infants introduced to
      complementary foods before 5 mo (P = 0.006), with those receiving support and
      resources (FAB and Combo groups combined; 55.6%) more likely to wait until at
      least 5 mo compared with controls (control and Sleep groups combined; 43.3%) (OR:
      1.52; 95% CI: 1.08, 2.16). However, there was no evidence they were more likely
      to wait until 6 mo of age (P = 0.52). Higher maternal age, higher parity, and a
      less positive attitude toward breastfeeding were positively associated, and
      drinking alcohol during pregnancy was negatively associated, with later age of
      introduction of complementary foods. CONCLUSIONS: Providing an LC and educational
      resources at 4-mo postpartum to predominantly well-educated, mainly European,
      women can delay the introduction of complementary foods until 5 mo of age, but
      not until the WHO recommendation of 6 mo. This trial was registered at
      clinicaltrials.gov as NCT00892983.

PMID- 25995281
TI  - Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose
      Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.
AB  - BACKGROUND: We previously reported that fish proteins can alleviate metabolic
      syndrome (MetS) in obese animals and human subjects. OBJECTIVES: We tested
      whether a salmon peptide fraction (SPF) could improve MetS in mice and explored
      potential mechanisms of action. METHODS: ApoB(100) only, LDL receptor knockout
      male mice (LDLR(-/-)/ApoB(100/100)) were fed a high-fat and -sucrose (HFS) diet
      (25 g/kg sucrose). Two groups were fed 10 g/kg casein hydrolysate (HFS), and 1
      group was additionally fed 4.35 g/kg fish oil (FO; HFS+FO). Two other groups were
      fed 10 g SPF/kg (HFS+SPF), and 1 group was additionally fed 4.35 g FO/kg
      (HFS+SPF+FO). A fifth (reference) group was fed a standard feed pellet diet. We
      assessed the impact of dietary treatments on glucose tolerance, adipose tissue
      inflammation, lipid homeostasis, and hepatic insulin signaling. The effects of
      SPF on glucose uptake, hepatic glucose production, and inducible nitric oxide
      synthase activity were further studied in vitro with the use of L6 myocytes, FAO
      hepatocytes, and J774 macrophages. RESULTS: Mice fed HFS+SPF or HFS+SPF+FO diets
      had lower body weight (protein effect, P = 0.024), feed efficiency (protein
      effect, P = 0.018), and liver weight (protein effect, P = 0.003) as well as lower
      concentrations of adipose tissue cytokines and chemokines (protein effect, P <=
      0.003) compared with HFS and HFS+FO groups. They also had greater glucose
      tolerance (protein effect, P < 0.001), lower activation of the mammalian target
      of rapamycin complex 1/S6 kinase 1/insulin receptor substrate 1
      (mTORC1/S6K1/IRS1) pathway, and increased insulin signaling in liver compared
      with the HFS and HFS+FO groups. The HFS+FO, HFS+SPF, and HFS+SPF+FO groups had
      lower plasma triglycerides (protein effect, P = 0.003; lipid effect, P = 0.002)
      than did the HFS group. SPF increased glucose uptake and decreased HGP and iNOS
      activation in vitro. CONCLUSIONS: SPF reduces obesity-linked MetS features in
      LDLR(-/-)/ApoB(100/100) mice. The anti-inflammatory and glucoregulatory
      properties of SPF were confirmed in L6 myocytes, FAO hepatocytes, and J774
      macrophages.

PMID- 25995283
TI  - Palm Oil Consumption Increases LDL Cholesterol Compared with Vegetable Oils Low
      in Saturated Fat in a Meta-Analysis of Clinical Trials.
AB  - BACKGROUND: Palm oil contains a high amount of saturated fat compared with most
      other vegetable oils, but studies have reported inconsistent effects of palm oil
      on blood lipids. OBJECTIVE: We systematically reviewed the effect of palm oil
      consumption on blood lipids compared with other cooking oils using data from
      clinical trials. METHODS: We searched PubMed and the Cochrane Library for trials
      of at least 2 wk duration that compared the effects of palm oil consumption with
      any of the predefined comparison oils: vegetable oils low in saturated fat, trans
      fat-containing partially hydrogenated vegetable oils, and animal fats. Data were
      pooled by using random-effects meta-analysis. RESULTS: Palm oil significantly
      increased LDL cholesterol by 0.24 mmol/L (95% CI: 0.13, 0.35 mmol/L; I(2) =
      83.2%) compared with vegetable oils low in saturated fat. This effect was
      observed in randomized trials (0.31 mmol/L; 95% CI: 0.20, 0.42 mmol/L) but not in
      nonrandomized trials (0.03 mmol/L; 95% CI: -0.15, 0.20 mmol/L; P-difference =
      0.02). Among randomized trials, only modest heterogeneity in study results
      remained after considering the test oil dose and the comparison oil type (I(2) =
      27.5%). Palm oil increased HDL cholesterol by 0.02 mmol/L (95% CI: 0.01, 0.04
      mmol/L; I(2) = 49.8%) compared with vegetable oils low in saturated fat and by
      0.09 mmol/L (95% CI: 0.06, 0.11 mmol/L; I(2) = 47.8%) compared with trans fat
      containing oils. CONCLUSIONS: Palm oil consumption results in higher LDL
      cholesterol than do vegetable oils low in saturated fat and higher HDL
      cholesterol than do trans fat-containing oils in humans. The effects of palm oil
      on blood lipids are as expected on the basis of its high saturated fat content,
      which supports the reduction in palm oil use by replacement with vegetable oils
      low in saturated and trans fat. This systematic review was registered with the
      PROSPERO registry at
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012002601#.VU3wvSGe
      RZ as CRD42012002601.

PMID- 25995282
TI  - Consuming High-Protein Soy Snacks Affects Appetite Control, Satiety, and Diet
      Quality in Young People and Influences Select Aspects of Mood and Cognition.
AB  - BACKGROUND: Data concerning the effects of afternoon snacking on ingestive
      behavior, mood, and cognition are limited. OBJECTIVE: The purpose of this study
      was to compare 1088 kJ of high-protein (HP) or high-fat (HF) afternoon snacks vs.
      no snacking on appetite, food intake, mood, and cognition in adolescents.
      METHODS: Thirty-one healthy adolescents (age: 17 +/- 1 y) consumed the following
      afternoon snacks (in randomized order) for 3 d: HP snack (26 g of protein/6 g of
      fat per 27 g of carbohydrates), HF snack (4 g of protein/12 g of fat per 32 g of
      carbohydrates), and no snack (NoS). On day 4 of each treatment, the participants
      completed an 8-h testing day containing pre- and postsnack appetite
      questionnaires, food cue-stimulated functional MRI brain scans, mood, cognitive
      function, and eating initiation. Ad libitum dinner and evening snacks were
      provided and assessed. RESULTS: HP, but not HF, delayed eating initiation vs. NoS
      (P < 0.05). Both snacks reduced appetite vs. NoS (P < 0.001) with HP eliciting
      greater reductions than HF (P < 0.05). Only HF led to reductions in corticolimbic
      activation in brain regions controlling food motivation/reward vs. NoS (P <
      0.01). Although no treatment differences in daily energy intake were detected, HP
      led to greater protein consumption than NoS (P < 0.05) and greater protein and
      lower fat consumption than HF (both, P < 0.05). HP led to fewer HF/high-sugar
      evening snacks than NoS (P < 0.01) and HF (P = 0.09). Although no treatment
      effects were detected for mood and cognition, HP tended to reduce confusion
      bewilderment (P = 0.07) and increase cognitive flexibility (P = 0.09), whereas
      NoS reduced tension-anxiety (P < 0.05) and vigor-activity (P < 0.05). CONCLUSION:
      Afternoon snacking, particularly on HP soy foods, improves appetite, satiety, and
      diet quality in adolescents, while beneficially influencing aspects of mood and
      cognition. This trial was registered at clinicaltrials.gov as NCT01781286.

PMID- 25995284
TI  - Undetectable pregnancy-associated plasma protein-A in antenatal serum Down's
      syndrome screening: a case of assay interference.
AB  - Serum pregnancy-associated plasma protein-A (PAPP-A) is measured in Down's
      syndrome screening, routinely offered to women in pregnancy. We present the case
      of an undetectable pregnancy-associated plasma protein-A concentration on the
      PerkinElmer AutoDELFIA system where immunoassay interference was suspected.
      Investigations performed, including dilution and recovery studies and antibody
      blocking tube incubations, all yielded serum pregnancy-associated plasma protein
      A concentrations of <25 mU/L. Pregnancy-associated plasma protein-A was also
      undetectable on two alternative pregnancy-associated plasma protein-A assays. An
      experimental manual Delfia procedure suggested the site of interference was
      between the secondary antibody and the pregnancy-associated plasma protein-A
      molecule. This case of negative interference in the PerkinElmer pregnancy
      associated plasma protein-A assay produced a falsely high Down's syndrome risk
      that might have led to an unnecessary invasive procedure with the potential for
      fetal loss. This highlights the need for Down's syndrome screening laboratories
      to be vigilant to immunoassay interference due to the significant impact of the
      results on patient decision outcome. 

PMID- 25995285
TI  - Lipoprotein lipase and atherosclerosis.
AB  - Lipoprotein lipase has long been known to hydrolyse triglycerides from
      triglycerides-rich lipoproteins. More recently, it has been shown to promote the
      binding of lipoproteins to various lipoprotein receptors. Evidence is also
      presented regarding the possible atherogenic role of lipoprotein lipase. In
      theory, lipoprotein lipase deficiency should help to clarify this question.
      However, the rarity of this condition means that it has not been possible to
      conduct epidemiological studies. An alternative approach is to investigate the
      correlation of lipoprotein lipase with onset of cardiovascular disease in
      prospective studies in large population-based cohorts. Complementary with this
      approach, animal models have been used to explore the atherogenicity of
      lipoprotein lipase expressed by macrophages. 

PMID- 25995286
TI  - Direct patient access to test results: implications for the laboratory.

PMID- 25995287
TI  - Propensity Score Methods for Analyzing Observational Data Like Randomized
      Experiments: Challenges and Solutions for Rare Outcomes and Exposures.
AB  - Randomized controlled trials are the "gold standard" for estimating the causal
      effects of treatments. However, it is often not feasible to conduct such a trial
      because of ethical concerns or budgetary constraints. We expand upon an approach
      to the analysis of observational data sets that mimics a sequence of randomized
      studies by implementing propensity score models within each trial to achieve
      covariate balance, using weighting and matching. The methods are illustrated
      using data from a safety study of the relationship between second-generation
      antipsychotics and type 2 diabetes (outcome) in Medicaid-insured children aged 10
      18 years across the United States from 2003 to 2007. Challenges in this data set
      include a rare outcome, a rare exposure, substantial and important differences
      between exposure groups, and a very large sample size. 

PMID- 25995288
TI  - Dynamic Variation in Sexual Contact Rates in a Cohort of HIV-Negative Gay Men.
AB  - Human immunodeficiency virus (HIV) transmission models that include variability
      in sexual behavior over time have shown increased incidence, prevalence, and
      acute-state transmission rates for a given population risk profile. This raises
      the question of whether dynamic variation in individual sexual behavior is a real
      phenomenon that can be observed and measured. To study this dynamic variation, we
      developed a model incorporating heterogeneity in both between-person and within
      person sexual contact patterns. Using novel methodology that we call iterated
      filtering for longitudinal data, we fitted this model by maximum likelihood to
      longitudinal survey data from the Centers for Disease Control and Prevention's
      Collaborative HIV Seroincidence Study (1992-1995). We found evidence for
      individual heterogeneity in sexual behavior over time. We simulated an epidemic
      process and found that inclusion of empirically measured levels of dynamic
      variation in individual-level sexual behavior brought the theoretical predictions
      of HIV incidence into closer alignment with reality given the measured per-act
      probabilities of transmission. The methods developed here provide a framework for
      quantifying variation in sexual behaviors that helps in understanding the HIV
      epidemic among gay men. 

PMID- 25995289
TI  - Applying Recovery Biomarkers to Calibrate Self-Report Measures of Energy and
      Protein in the Hispanic Community Health Study/Study of Latinos.
AB  - We investigated measurement error in the self-reported diets of US
      Hispanics/Latinos, who are prone to obesity and related comorbidities, by
      background (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South
      American) in 2010-2012. In 477 participants aged 18-74 years, doubly labeled
      water and urinary nitrogen were used as objective recovery biomarkers of energy
      and protein intakes. Self-report was captured from two 24-hour dietary recalls.
      All measures were repeated in a subsample of 98 individuals. We examined the bias
      of dietary recalls and their associations with participant characteristics using
      generalized estimating equations. Energy intake was underestimated by 25.3% (men,
      21.8%; women, 27.3%), and protein intake was underestimated by 18.5% (men, 14.7%;
      women, 20.7%). Protein density was overestimated by 10.7% (men, 11.3%; women,
      10.1%). Higher body mass index and Hispanic/Latino background were associated
      with underestimation of energy (P<0.05). For protein intake, higher body mass
      index, older age, nonsmoking, Spanish speaking, and Hispanic/Latino background
      were associated with underestimation (P<0.05). Systematic underreporting of
      energy and protein intakes and overreporting of protein density were found to
      vary significantly by Hispanic/Latino background. We developed calibration
      equations that correct for subject-specific error in reporting that can be used
      to reduce bias in diet-disease association studies.

PMID- 25995291
TI  - Associations of Region-Specific Foot Pain and Foot Biomechanics: The Framingham
      Foot Study.
AB  - BACKGROUND: Specific regions of the foot are responsible for the gait tasks of
      weight acceptance, single-limb support, and forward propulsion. With region foot
      pain, gait abnormalities may arise and affect the plantar pressure and force
      pattern utilized. Therefore, this study's purpose was to evaluate plantar
      pressure and force pattern differences between adults with and without region
      specific foot pain. METHODS: Plantar pressure and force data were collected on
      Framingham Foot Study members while walking barefoot at a self-selected pace.
      Foot pain was evaluated by self-report and grouped by foot region (toe, forefoot,
      midfoot, or rearfoot) or regions (two or three or more regions) of pain.
      Unadjusted and adjusted linear regression with generalized estimating equations
      was used to determine associations between feet with and without foot pain.
      RESULTS: Individuals with distal foot (forefoot or toes) pain had similar maximum
      vertical forces under the pain region, while those with proximal foot (rearfoot
      or midfoot) pain had different maximum vertical forces compared to those without
      regional foot pain (referent). During walking, there were significant differences
      in plantar loading and propulsion ranging from 2% to 4% between those with and
      without regional foot pain. Significant differences in normalized maximum
      vertical force and plantar pressure ranged from 5.3% to 12.4% and 3.4% to 24.1%,
      respectively, between those with and without regional foot pain. CONCLUSIONS:
      Associations of regional foot pain with plantar pressure and force were different
      by regions of pain. Region-specific foot pain was not uniformly associated with
      an increase or decrease in loading and pressure patterns regions of pain.

PMID- 25995292
TI  - High levels of macrolide resistance-associated mutations in Mycoplasma genitalium
      warrant antibiotic susceptibility-guided treatment.
AB  - OBJECTIVES: Mycoplasma genitalium is a sexually transmitted pathogen, and
      infection with it is usually treated with macrolides. Unfortunately, emerging
      resistance to the macrolides has been associated with mutations in region V of
      the 23S rRNA gene. The aim of this retrospective study was to describe the
      incidence of macrolide resistance-associated mutations in M. genitalium from
      patients in the Netherlands. METHODS: All urogenital samples obtained from
      patients visiting a general practitioner or hospital in the east of the
      Netherlands that tested positive using the routine M. genitalium real-time PCR
      (February 2012-November 2014) were included. Following a PCR targeting the 23S
      rRNA gene, sequencing of the PCR fragments was performed to identify possible
      macrolide resistance-associated mutations. RESULTS: Forty-eight of the 153
      samples (31.4%) included in this study contained a mutation in the 23S rRNA gene.
      This was reduced to 44/146 (30.1%) if only samples from unique patients were
      included. The predominant mutations identified were A2058G (16/44; 36.3%), A2059G
      (14/44; 31.8%) and a unique high proportion of A2058T (12/44; 27.3%). Treatment
      failure was observed in four patients initially infected with M. genitalium
      containing macrolide resistance-associated mutations, while in one of these
      patients subsequent treatment with moxifloxacin resulted in a microbiological
      cure. CONCLUSIONS: This study shows that macrolide resistance-associated
      mutations in M. genitalium occur with a high frequency. In contrast to studies
      from other regions, Dutch M. genitalium isolates carry the A2058T mutation at
      high frequency. Our data confirm the need for prospective detection of macrolide
      resistance-associated mutations prior to treating patients.

PMID- 25995293
TI  - Sickle-cell disease: a call to action.

PMID- 25995290
TI  - Reconsidering the Role of Mitochondria in Aging.
AB  - BACKGROUND: Mitochondrial dysfunction has long been considered a major
      contributor to aging and age-related diseases. Harman's Mitochondrial Free
      Radical Theory of Aging postulated that somatic mitochondrial DNA mutations that
      accumulate over the life span cause excessive production of reactive oxygen
      species that damage macromolecules and impair cell and tissue function. Indeed,
      studies have shown that maximal oxidative capacity declines with age while
      reactive oxygen species production increases. Harman's hypothesis has been
      seriously challenged by recent studies showing that reactive oxygen species evoke
      metabolic health and longevity, perhaps through hormetic mechanisms that include
      autophagy. The purpose of this review is to scan the ever-growing literature on
      mitochondria from the perspective of aging research and try to identify priority
      questions that should be addressed in future research. METHODS: A systematic
      search of peer-reviewed studies was performed using PubMed. Search terms included
      (i) mitochondria or mitochondrial; (ii) aging, ageing, older adults or elderly;
      and (iii) reactive oxygen species, mitochondria dynamics, mitochondrial
      proteostasis, cytosol, mitochondrial-associated membranes, redox homeostasis,
      electron transport chain, electron transport chain efficiency, epigenetic
      regulation, DNA heteroplasmy. RESULTS: The importance of mitochondrial biology as
      a trait d'union between the basic biology of aging and the pathogenesis of age
      related diseases is stronger than ever, although the emphasis has moved from
      reactive oxygen species production to other aspects of mitochondrial physiology,
      including mitochondrial biogenesis and turnover, energy sensing, apoptosis,
      senescence, and calcium dynamics. CONCLUSIONS: Mitochondria could play a key role
      in the pathophysiology of aging or in the earlier stages of some events that lead
      to the aging phenotype. Therefore, mitochondria will increasingly be targeted to
      prevent and treat chronic diseases and to promote healthy aging.

PMID- 25995294
TI  - LEGAL BASES FOR DISCLOSING CONFIDENTIAL PATIENT INFORMATION FOR PUBLIC HEALTH:
      DISTINGUISHING BETWEEN HEALTH PROTECTION AND HEALTH IMPROVEMENT.
AB  - The disclosure of confidential patient data without an individual's explicit
      consent should be for purposes that persons have reason to both expect and
      accept. We do not currently have the required level of clarity or consistency in
      understanding regarding the disclosure of confidential patient information for
      public health purposes to support effective public dialogue. The Health Service
      (Control of Patient Information) Regulations 2002 establish a legal basis in
      England and Wales for data to be disclosed for public health purposes without
      patient consent. Under the Regulations, there is more than one potential route
      towards lawful processing: Data may be processed for public health purposes under
      both Regulations 3 and 5. The alternatives have different safeguards and
      conditions attached, and their respective applicability to processing for
      purposes of public health improvement is currently unclear and subject to review.
      Beyond the need for clarity regarding the safeguards applicable to processing for
      particular public health purposes, there are reasons to prefer recognition that
      Regulation 5 is the most appropriate legal basis for disclosure when the purpose
      is public health improvement rather than public health protection. Where health
      improvement, rather than protection, is the aim, there is no justification for
      discarding the additional safeguards associated with processing under Regulation
      5. 

PMID- 25995295
TI  - Occupational inhalational exposure and serum GM-CSF autoantibody in pulmonary
      alveolar proteinosis.
AB  - OBJECTIVES: Although the serum granulocyte-macrophage colony stimulating factor
      autoantibody (GMAb) levels have been recognised as a diagnostic marker in primary
      pulmonary alveolar proteinosis (PAP), their role in PAP with occupational
      inhalational exposure (PAPo) remains unclear. METHODS: Forty-five consecutive
      patients with PAP were enrolled. Each patient with PAP was assessed for baseline
      clinical characteristics, chest high-resolution CT (HRCT), serum GMAb and
      occupational exposure. Fifty healthy controls were included to define normal
      ranges for GMAb levels. Ninety-seven hospital controls with other respiratory
      diseases were included to establish prevalence of a history of occupational
      inhalation exposure. RESULTS: According to the serum GMAb cut-off value of 2.39
      MUg/mL, 84.4% of the recruited patients with PAP had positive serum GMAb with a
      median level of 28.7 MUg/mL, defined as autoimmune PAP, and the remaining 15.6%
      had negative serum GMAb with a median level of 0.16 MUg/mL, defined as non
      autoimmune PAP. Also, 34.2% of patients with autoimmune PAP had a history of
      occupational inhalational exposure, which was not significantly higher than that
      of hospital controls (34.2% vs 19.6%, p=0.072). Four patients with PAPo showed
      negative GMAb. Their arterial oxygen tension, pulmonary function parameters and
      chest HRCT features were significantly different when compared with patients with
      autoimmune PAP (p<0.05). These four non-autoimmune occupational lung disease
      cases culminated in 3 deaths and a lung transplant. CONCLUSIONS: A number of
      patients with PAP who may have occupational inhalational exposure and negative
      serum GMAb represent a high possibility of silicoproteinosis and very poor
      survival.

PMID- 25995296
TI  - Occupational physical demand and risk of hip fracture in older women.
AB  - OBJECTIVES: Hip fractures are leading causes of disability, morbidity and
      mortality among older women. Since physical activity helps maintain physical
      functioning and bone mineral density, occupational physical demand may influence
      fracture risk. This study investigates the association of occupational physical
      demand with hip fracture incidence among women. METHODS: The Women's Health
      Initiative Observational Study is a multiethnic cohort of 93,676 postmenopausal
      women, 50-79 years of age at enrolment, enrolled from 1994 to 1998 at 40
      geographically diverse clinical centres throughout the USA. Outcomes including
      hip fractures were assessed annually and up to 3 jobs held since age 18 years
      were reported by each woman. Occupational physical demand levels were assigned
      for each job through linkage of occupational titles with Standard Occupational
      Codes and the Occupational Information Network. Average, cumulative and peak
      physical demand scores both before and after menopause and throughout women's
      work life were estimated. RESULTS: Women were followed through 2010 for an
      average of 11.5 years; 1834 hip fractures occurred during this time. We did not
      observe an overall association of occupational physical demand with subsequent
      risk of hip fracture after adjusting for age, race/ethnicity, birth region and
      education. CONCLUSIONS: Previous research on occupations and hip fracture risk in
      women is inconclusive. This study was able to take critical risk periods into
      account and control for confounding factors in a large cohort of older women to
      show that overall occupational physical demand neither increases nor decreases
      risk of hip fracture later in life.

PMID- 25995297
TI  - Cytoplasmic and nuclear leptin expression in lacrimal gland tumours: a pilot
      study.
AB  - PURPOSE: To investigate leptin expression and distribution in the tissue of
      lacrimal gland epithelial tumours, and leptin concentration in the tears secreted
      by these tumours. METHODS: Clinical records and microscopic slides of six
      pleomorphic adenoma (PA), three adenoid cystic carcinoma (ACC), and one chronic
      sclerosing dacryoadenitis (CSD) cases were reviewed. Normal-appearing gland
      tissue adjacent to tumours from patients with PA served as controls. Tissue
      leptin expression and distribution were assessed using leptin
      immunohistochemistry staining. Preoperative and postoperative leptin
      concentrations in tears were measured in the tumour-affected eye in two patients
      with PA, two with ACC and one with CSD, and in the contralateral eye in one
      patient with ACC and one with CSD. RESULTS: Moderate cytoplasmic staining was
      observed in all tumour-adjacent morphologically normal tissue, PA, ACC and CSD
      tissues. ACC tissues revealed moderate nuclear staining in tumour cells, whereas
      other tissues did not reveal leptin nuclear staining (p=0.012). Leptin in tears
      was not detected in the eyes of patients with PA preoperatively and
      postoperatively. However, leptin was detected in tears of patients with ACC and
      CSD preoperatively, and its concentration markedly decreased at 1 month
      postoperatively. Leptin was not detected in any sample from the contralateral
      eyes of patients for which such samples were available. CONCLUSIONS: The leptin
      concentration in tears was greater in patients with ACC than in those with PA.
      Leptin nuclear staining was only observed in the ACC tissue. Further
      investigations should be conducted to identify the cause and significance of
      these findings.

PMID- 25995298
TI  - Parity and the risk of cataract: a cross-sectional analysis in the Dongfeng
      Tongji cohort study.
AB  - AIMS: Epidemiological evidence showed that prevalence rates of cataract were
      higher in women than in men. Female reproductive factors were hypothesised to be
      linked with this sex difference. In this study, we explored possible effects of
      parity and reproductive factors on the risk of cataract. METHODS: Women (14 337
      total; aged 45-86 years) were recruited from the Dongfeng-Tongji cohort study.
      All subjects completed baseline questionnaires and medical examinations and
      provided baseline blood samples. Cataract was diagnosed by the ophthalmologist in
      the ocular examination. Logistic regression models were used to evaluate the
      association between parity and the risk of cataract. RESULTS: The prevalence rate
      of cataract in the study population was 6.8% (972/14 337). After adjustment for
      potential confounders, women who had undergone two, three, and four or more live
      births had 1.52 times (95% CI 1.13 to 2.04), 1.67 times (95% CI 1.27 to 2.29) and
      1.72 times (95% CI 1.22 to 2.42), respectively, higher risk of cataract compared
      with women who had undergone one live birth. The risk increased by an estimated
      11.3% for each additional live birth. Women who had undergone hormone replacement
      therapy (OR 1.61; 95% CI 1.05 to 2.47), had diabetes mellitus (OR 1.33; 95% CI
      1.11 to 1.58) and/or had the habit of drinking alcohol (OR 1.51; 95% CI 1.08 to
      2.10) had a higher risk of cataract. Neither menopause status nor history of
      contraceptive use was associated with cataract. CONCLUSIONS: The findings
      suggested that parity was an independent risk factor for the development of
      cataract in Chinese women.

PMID- 25995299
TI  - Accuracy of a technology-assisted eye exam in evaluation of referable diabetic
      retinopathy and concomitant ocular diseases.
AB  - BACKGROUND/AIMS: Digital retinal imaging using store-and-forward technology is
      used to screen for diabetic retinopathy (DR). Its usefulness in detecting non
      diabetic eye diseases is uncertain. We determined the level of agreement between
      teleretinal imaging supplemented with visual acuity and intraocular pressure
      (IOP) measurements (ie, technology-assisted eye (TAE) exam) and a comprehensive
      eye exam in evaluation for DR and non-diabetic ocular conditions. METHODS: We
      conducted a prospective, observational study with two parallel evaluations.
      Patients with diabetes (n=317) had a TAE exam and a comprehensive eye exam on the
      same day. A subset of participants with normal baseline exams (n=72) had follow
      up exams 1 year later. We measured the level of agreement for referable ocular
      findings. RESULTS: Agreement for referable ocular findings was moderate (n=389,
      agreement: 77%; kappa: 0.55), due in part to ungradable exams (22%). However,
      about half of the ungradable exams had findings that warranted referral. There
      was substantial agreement for follow-up exams (n=72, agreement: 93%; kappa:
      0.63). Among all gradable exams (n=303), the TAE exam had 86% sensitivity and 84%
      specificity for referable ocular findings, with high agreement (>=94%) for DR and
      other major ocular diagnoses. CONCLUSIONS: There was moderate-to-substantial
      agreement between a TAE exam and a comprehensive eye exam for referable ocular
      findings in patients with diabetes. Ungradable exams were a frequent marker of
      ocular pathology. Teleretinal imaging may be a useful evaluation for both
      diabetic and non-diabetic ocular conditions.

PMID- 25995300
TI  - Role of macular hole angle in macular hole closure.
AB  - AIM: To evaluate correlation of various spectral-domain optical coherence
      tomography (SD-OCT) parameters including macular hole angle as well as various
      indices with anatomical and visual outcomes after idiopathic macular hole repair
      surgery. METHODS: Retrospective study of 137 eyes of 137 patients who underwent
      idiopathic macular hole repair surgery between January 2008 and January 2014 was
      performed. Various qualitative parameters such as presence of vitreomacular
      traction, epiretinal membrane and cystic edges at the macular hole as well as
      quantitative parameters such as maximum diameter on the apex of the hole, minimum
      diameter between edges, nasal and temporal vertical height, longest base diameter
      and macular hole angle between the retinal edge and the retinal pigment
      epithelium were noted. Indices including hole form factor, Macular Hole Index
      (MHI), Diameter Hole Index and Tractional Hole Index (THI) were calculated.
      Univariate and multivariate regression analysis was performed separately for
      final visual acuity (VA) and type of closure as dependent variable in relation to
      SD-OCT parameters as independent variables. RESULTS: On multivariate regression
      only minimum diameter between edges (p<=0.01) and longest base diameter (p<=0.03)
      were correlated significantly with both, type 1 closure and final VA. Among the
      indices, significant correlation of MHI (p=0.009) was noted with type of closure
      and that of THI with final VA (p=0.017). CONCLUSIONS: Our study shows no
      significant correlation between macular hole angle and hole closure. Minimum
      diameter between the edges and longest diameter of the hole are best predictors
      of hole closure and postoperative VA.

PMID- 25995301
TI  - Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase
      III randomized adjuvant breast cancer trials.
AB  - BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are emerging as strong
      prognostic factor for early breast cancer patients, especially in the triple
      negative subtype. Here, we aim to validate previous findings on the prognostic
      role of TIL in the context of two randomized adjuvant trials and to investigate
      whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines.
      PATIENTS AND METHODS: A total of 816 patients enrolled and treated at the Gustave
      Roussy in the context of two multicentric randomized trials comparing adjuvant
      anthracyclines versus no chemotherapy were included in the present analysis.
      Primary end point was overall survival (OS). Hematoxilin and eosin slides of
      primary tumors were retrieved and evaluated for the percentage of intratumoral
      (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL
      breast cancer adopting previously validated cutoffs. RESULTS: TIL were assessable
      for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen
      receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It
      TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85,
      95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P =
      0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous
      TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates
      were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR
      0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL
      versus low-TIL, respectively (HR 0.46, 95% CI 0.20-1.11, P = 0.08). Either
      continuous or binary TIL variables did not predict for the efficacy of
      anthracyclines. Test for interaction P value was not significant in the whole
      study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-). CONCLUSIONS: We
      confirmed the prognostic role of TIL in triple-negative early breast cancer and
      suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL
      should not be used as a parameter to select patients for anthracyclines
      chemotherapy.

PMID- 25995302
TI  - HIV Susceptibility Among Migrant Miners in Chokwe: A Case Study.
AB  - This article examines the association between risky sexual behavior and HIV risk
      perception among miners. A cross-sectional survey (n = 293) was conducted with
      miners who worked in South African mines and lived in the Chokwe district of Gaza
      Province in southern Mozambique. The study used ordinary logistic and cumulative
      logistic models to understand what drives miners to HIV susceptibility. The study
      revealed that most miners were at risk of HIV infection as a result of risky
      sexual behavior. However, there was a strong negative association between risky
      sexual behavior and HIV risk perception. Seventy percent of the miners practicing
      risky sexual behavior reported low HIV risk perception. This demonstrates that
      miners tend to underestimate their HIV risk, which makes them more susceptible to
      contracting HIV. Risk perception among miners is related to a range of factors,
      both individual and environmental. Informed risk awareness is essential for these
      men to adopt preventive measures against HIV/AIDS. Therefore, it is important to
      consider cultural beliefs, as they influence the understanding of HIV risk
      perception.

PMID- 25995303
TI  - The Japanese Surgical Reimbursement System Fails to Reflect Resource Utilization.
AB  - The goal of this study was to examine the current Japanese surgical payment
      system from the viewpoint of resource utilization. We collected data from
      surgical records in Teikyo University's electronic medical record system from
      April 1 through September 30, 2013. We defined the decision-making unit as a
      surgeon with the highest academic rank in the surgery. Inputs were defined as: 1)
      the number of medical doctors who assisted surgery and 2) the time of operation
      from skin incision to closure. An output was defined as the surgical fee. We
      calculated each surgeon's efficiency score using the output-oriented Banker
      Charnes-Cooper model of data envelopment analysis. We compared the efficiency
      scores of each surgical specialty using the Kruskal-Wallis and Steel methods. We
      analyzed 2,825 surgical procedures performed by 103 surgeons. The difference in
      efficiency scores was significant (P = 0.0001). The thoracic surgeons were the
      most efficient and were more efficient than plastic, obstetric and gynecologic,
      urologic, otorhinolaryngologic, orthopedic, general, and emergency surgeons (P <
      0.05). We demonstrated that surgeons' efficiency in operating rooms was
      significantly different among surgical specialties. This suggests that the
      Japanese surgical reimbursement scales fails to reflect resource utilization. 

PMID- 25995304
TI  - Predictors of Payer Mix and Financial Performance Among Safety Net Hospitals
      Prior to the Affordable Care Act.
AB  - The objective of this study was to use audited hospital financial statements to
      identify predictors of payer mix and financial performance in safety net
      hospitals prior to the Affordable Care Act. We analyzed the 2010 financial
      statements of 98 large, urban safety net hospital systems in 34 states,
      supplemented with data on population demographics, hospital features, and state
      policies. We used multivariate regression to identify independent predictors of
      three outcomes: 1) Medicaid-reliant payer mix (hospitals for which at least 25%
      of hospital days are paid for by Medicaid); 2) safety net revenue-to-cost ratio
      (Medicaid and Medicare Disproportionate Share Hospital payments and local
      government transfers, divided by charity care costs and Medicaid payment
      shortfall); and 3) operating margin. Medicaid-reliant payer mix was positively
      associated with more inclusive state Medicaid eligibility criteria and more
      minority patients. More inclusive Medicaid eligibility and higher Medicaid
      reimbursement rates positively predicted safety net revenue-to-cost ratio.
      University governance was the strongest positive predictor of operating margin.
      Safety net hospital financial performance varied considerably. Academic hospitals
      had higher operating margins, while more generous Medicaid eligibility and
      reimbursement policies improved hospitals' ability to recoup costs. Institutional
      and state policies may outweigh patient demographics in the financial health of
      safety net hospitals. 

PMID- 25995305
TI  - Education Improves Public Health and Promotes Health Equity.
AB  - This article describes a framework and empirical evidence to support the argument
      that educational programs and policies are crucial public health interventions.
      Concepts of education and health are developed and linked, and we review a wide
      range of empirical studies to clarify pathways of linkage and explore
      implications. Basic educational expertise and skills, including fundamental
      knowledge, reasoning ability, emotional self-regulation, and interactional
      abilities, are critical components of health. Moreover, education is a
      fundamental social determinant of health - an upstream cause of health. Programs
      that close gaps in educational outcomes between low-income or racial and ethnic
      minority populations and higher-income or majority populations are needed to
      promote health equity. Public health policy makers, health practitioners and
      educators, and departments of health and education can collaborate to implement
      educational programs and policies for which systematic evidence indicates clear
      public health benefits. 

PMID- 25995306
TI  - A Critique of Health System Performance Measurement.
AB  - Health system performance measurement is a ubiquitous phenomenon. Many authors
      have identified multiple methodological and substantive problems with performance
      measurement practices. Despite the validity of these criticisms and their cross
      national character, the practice of health system performance measurement
      persists. Theodore Marmor suggests that performance measurement invokes an
      "incantatory response" wrapped within "linguistic muddle." In this article, I
      expand upon Marmor's insights using Pierre Bourdieu's theoretical framework to
      suggest that, far from an aberration, the "linguistic muddle" identified by
      Marmor is an indicator of a broad struggle about the representation and
      classification of public health services as a public good. I present a case study
      of performance measurement from Alberta, Canada, examining how this
      representational struggle occurs and what the stakes are. 

PMID- 25995307
TI  - A Critique of Grossman's Canonical Model of Health Capital.
AB  - In the health economics literature, the demand for health and market health
      inputs is dominated by adaptations of Grossman's health capital model. The model
      has been widely used to explore a wide range of issues related to health,
      socioeconomic inequalities in health, demand for medical care, health
      preventions, occupational choice, and retirement decisions. The commodity of
      health is viewed as a durable capital stock that yields a flow of healthy time or
      illness-free time, that depreciates with age, and that can be augmented with the
      help of market health inputs and own time. The purpose of this article is to
      provide a comprehensive critical review of the model. Underlying Grossman's model
      are a faulty conceptual framework and assumptions that tend to exaggerate the
      degree of control consumers/patients may have over their state of health and
      survival. The assumption of full information about one's state of health and the
      efficacy of various health inputs abstracts away from the problems posed by the
      agency relationship under uncertainty and informational asymmetry. Grossman's
      individualistic and mechanistic view of health strips health capital and its
      production of much of their biological/physiological content and their
      interactions with the individual's social and physical environment. 

PMID- 25995308
TI  - Evidence-based hamstring injury prevention is not adopted by the majority of
      Champions League or Norwegian Premier League football teams: the Nordic Hamstring
      survey.
AB  - BACKGROUND: The Nordic hamstring (NH) exercise programme was introduced in 2001
      and has been shown to reduce the risk of acute hamstring injuries in football by
      at least 50%. Despite this, the rate of hamstring injuries has not decreased over
      the past decade in male elite football. AIM: To examine the implementation of the
      NH exercise programme at the highest level of male football in Europe, the UEFA
      Champions League (UCL), and to compare this to the Norwegian Premier League,
      Tippeligaen, where the pioneer research on the NH programme was conducted.
      DESIGN: Retrospective survey. SETTING/PARTICIPANTS: 50 professional football
      teams, 32 from the UCL and 18 from Tippeligaen. METHODS: A questionnaire, based
      on the Reach, Efficacy, Adoption, Implementation and Maintenance framework,
      addressing key issues related to the implementation of the NH programme during
      three seasons from 2012 through 2014, was distributed to team medical staff using
      electronic survey software. RESULTS: The response rate was 100%. Of the 150 club
      seasons covered by the study, the NH programme was completed in full in 16
      (10.7%) and in part in an additional 9 (6%) seasons. Consequently, 125 (83.3%)
      club-seasons were classified as non-compliant. There was no difference in
      compliance between the UCL and Tippeligaen in any season (chi(2): 0.41 to 0.52).
      CONCLUSIONS: Adoption and implementation of the NH exercise programme at the
      highest levels of male football in Europe is low; too low to expect any overall
      effect on acute hamstring injury rates.

PMID- 25995309
TI  - Utility of adaptive control processing for the interpretation of digital
      mammograms.
AB  - Background Adaptive control processing for mammography (ACM) is a novel program
      that automatically sets up appropriate image-processing parameters for individual
      mammograms (MMGs) by analyzing the focal and whole breast histogram. Purpose To
      investigate whether ACM improves the image contrast of digital MMGs and whether
      it improves radiologists' diagnostic performance in reading of MMGs. Material and
      Methods One hundred normal cases for image quality assessment and another 100
      cases (50 normal and 50 cancers) for observer performance assessment were
      enrolled. All mammograms were examined with and without ACM. Five radiologists
      assessed the intra- and extra-mammary contrast of 100 normal MMGs, and the mean
      scores of the intra- and extra-mammary contrast were compared between MMGs with
      and without ACM in both the dense and non-dense group. They classified 100 MMGs
      into BI-RADS categories 1-5, and were asked to rate the images on a scale of 0 to
      100 for the likelihood of the presence of category 3-5 lesions in each breast.
      Detectability of breast cancer, reading time, and frequency of window adjustment
      were compared between MMGs with and without ACM. Results ACM improved the intra
      mammary contrast in both the dense and non-dense group but degraded extra-mammary
      contrast in the dense group. There was no significant difference in detectability
      of breast cancer between MMGs with and without ACM. Frequency of window
      adjustment without ACM was significantly higher than that with ACM. Reading time
      without ACM was significantly longer than that with ACM. Conclusion ACM improves
      the image contrast of MMGs and shortens reading time.

PMID- 25995310
TI  - A longitudinal fMRI investigation in acute post-traumatic stress disorder (PTSD).
AB  - Background Neuroimaging studies have implicated limbic, paralimbic, and
      prefrontal cortex in the pathophysiology of chronic post-traumatic stress
      disorder (PTSD). However, little is known about the neural substrates of acute
      PTSD and how they change with symptom improvement. Purpose To examine the neural
      circuitry underlying acute PTSD and brain function changes during clinical
      recovery from this disorder. Material and Methods Nineteen acute PTSD patients
      and nine non-PTSD subjects who all experienced a devastating mining accident
      underwent clinical assessment as well as functional magnetic resonance imaging
      (fMRI) scanning while viewing trauma-related and neutral pictures. Two years
      after the accident, a subgroup of 17 patients completed a second clinical
      evaluation, of which 13 were given an identical follow-up scan. Results Acute
      PTSD patients demonstrated greater activation in the vermis and right posterior
      cingulate, and greater deactivation in the bilateral medial prefrontal cortex and
      inferior parietal lobules than controls in the traumatic versus neutral
      condition. At follow-up, PTSD patients showed symptom reduction and decreased
      activation in the right middle frontal gyrus, bilateral posterior
      cingulate/precuneus, and cerebellum. Correlation results confirmed these findings
      and indicated that brain activation in the posterior cingulate/precuneus and
      vermis was predictive of PTSD symptom improvement. Conclusion The findings
      support the involvement of the medial prefrontal cortex, inferior parietal
      lobule, posterior cingulate, and vermis in the pathogenesis of acute PTSD. Brain
      activation in the vermis and posterior cingulate/precuneus appears to be a
      biological marker of recovery potential from PTSD. Furthermore, decreased
      activation of the middle frontal gyrus, posterior cingulate/precuneus, and
      cerebellum may reflect symptom improvement.

PMID- 25995312
TI  - B1 homogeneity of breast MRI using RF shimming with individual specific values in
      volunteers simulating patients after mastectomy.
AB  - Background Magnetic resonance imaging (MRI) using a 3-T MRI scanner is now widely
      used for clinical examinations. However, B1 inhomogeneity becomes larger with MRI
      scanners using 3-T and higher. It especially becomes a problem in the breast. To
      improve B1 homogeneity, a RF shimming technique has been developed. Purpose To
      evaluate the B1 homogeneity of breast MRI using RF shimming with individual
      specific values for subjects after mastectomy. Material and Methods The subjects
      are healthy female volunteers who underwent normal breast imaging, followed by
      imaging of one breast while the other breast was bound tightly to the chest by
      bleached cotton cloths (simulating volunteers after mastectomy). B1 mappings were
      performed with RF shimming using two techniques: (i) optimized fixed value; and
      (ii) individual specific values using a 3-T MRI scanner. The means and standard
      deviations of the B1 maps for all slices in the breast were measured and compared
      between the fixed value and the individual specific value cases. Results For
      normal volunteers, the breast B1 variation was not statistically significantly
      different between the RF shimming techniques. For volunteers after simulated
      surgery, the breast B1 variation was (1.02 +/- 0.29) with the fixed value and
      (0.98 +/- 0.22) with the individual specific value ( P < 0.01). With the
      individual specific optimization, B1 variation for all slices in the breast was
      improved for volunteers after simulated surgery. Conclusion RF shimming with
      individual specific values has the potential to improve the B1 homogeneity of
      breast MRI in patients after mastectomy.

PMID- 25995311
TI  - MRI and comparison mammography: a worthy diagnostic alliance for breast
      microcalcifications?
AB  - BACKGROUND: There is a lack of data concerning diagnostic performance of magnetic
      resonance imaging (MRI) in patients with new or increasing microcalcifications.
      PURPOSE: To evaluate suspicious microcalcifications by using comparison
      mammography, MRI, and a combination of both methods. MATERIAL AND METHODS: Our
      study group consisted of 55 patients with mammographically detected BI-RADS
      (Breast Imaging Reporting and Data System) 3-5 microcalcifications for whom
      comparison mammograms were available. All patients underwent breast MRI before
      SVAB (stereotactic vacuum-assisted biopsy). Diagnostic performances of comparison
      mammography and MRI were evaluated, as well as the combination of the respective
      imaging findings. RESULTS: Of the 55 microcalcification cases, 35 showed
      progression and 20 were stable between interval screenings. The negative
      predictive value (NPV) of comparison mammography was 100%, whereas the NPV of MRI
      was 92%. However, the specificity of combination of findings was 97%,
      significantly higher than the 42% specificity of comparison mammography (P <
      0.001). Additionally, the positive predictive value of combination of findings
      was 93% versus 44% of comparison mammography (P = 0.001). CONCLUSION: A biopsy is
      recommended when MRI positive lesion corresponding the area of new or increasing
      mammographic microcalcifications is detected. Patients with stable
      microcalcifications can continue follow-up mammography, regardless of MRI result.

PMID- 25995313
TI  - Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial
      Infarction: Insights From the Treatment with ADP Receptor Inhibitors:
      Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary
      Syndrome (TRANSLATE-ACS) Study.
AB  - BACKGROUND: Aspirin is the most widely used antiplatelet drug postmyocardial
      infarction, yet its optimal maintenance dose after percutaneous coronary
      intervention with stenting remains uncertain. METHODS AND RESULTS: We compared
      outcomes of 10 213 patients with myocardial infarction who underwent percutaneous
      coronary intervention and were discharged on dual-antiplatelet therapy at 228 US
      hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment
      of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS)
      study from 2010 to 2012. Major adverse cardiovascular events and bleeding within
      6 months postdischarge were compared between high-dose (325 mg) and low-dose
      aspirin (81 mg) by using regression models with inverse probability-weighted
      propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at
      discharge. Major adverse cardiovascular events risk was not significantly
      different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted
      hazard ratio, 0.99; 95% confidence interval, 0.85-1.17). High-dose aspirin use
      was associated with greater risk of any Bleeding Academic Research Consortium
      defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio,
      1.19; 95% confidence interval, 1.06-1.33), driven mostly by minor Bleeding
      Academic Research Consortium type 1 or 2 bleeding events not requiring
      hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95%
      confidence interval, 1.05-1.34). Bleeding events requiring hospitalization were
      similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds
      ratio, 1.22; 95% confidence interval, 0.87-1.70). Similar associations were
      observed in landmark analyses accounting for aspirin dosing change over time, and
      across subgroup analyses by age, sex, baseline aspirin use, and type of ADP
      receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). CONCLUSIONS: Among
      percutaneous coronary intervention-treated patients with myocardial infarction,
      high-maintenance-dose aspirin was associated with similar rates of major adverse
      cardiovascular events, but a greater risk of minor bleeding than those discharged
      on low-dose aspirin.

PMID- 25995314
TI  - Inside-Out Signaling: Moving the AT1 Receptor in to Get the Message Out.

PMID- 25995315
TI  - Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional
      Angiotensin II Type 1 Receptors.
AB  - BACKGROUND: Whether biomechanical force on the heart can induce exosome secretion
      to modulate cardiovascular function is not known. We investigated the secretion
      and activity of exosomes containing a key receptor in cardiovascular function,
      the angiotensin II type I receptor (AT1R). METHODS AND RESULTS: Exosomes
      containing AT1Rs were isolated from the media overlying AT1R-overexpressing cells
      exposed to osmotic stretch and from sera of mice undergoing cardiac pressure
      overload. The presence of AT1Rs in exosomes was confirmed by both electron
      microscopy and radioligand receptor binding assays and shown to require beta
      arrestin2, a multifunctional adaptor protein essential for receptor trafficking.
      We show that functional AT1Rs are transferred via exosomes in an in vitro model
      of cellular stretch. Using mice with global and cardiomyocyte conditional
      deletion of beta-arrestin2, we show that under conditions of in vivo pressure
      overload the cellular source of the exocytosis of exosomes containing AT1R is the
      cardiomyocyte. Exogenously administered AT1R-enriched exosomes target
      cardiomyocytes, skeletal myocytes, and mesenteric resistance vessels and are
      sufficient to confer blood pressure responsiveness to angiotensin II infusion in
      AT1R knockout mice. CONCLUSIONS: AT1R-enriched exosomes are released from the
      heart under conditions of in vivo cellular stress to likely modulate vascular
      responses to neurohormonal stimulation. In the context of the whole organism, the
      concept of G protein-coupled receptor trafficking should consider circulating
      exosomes as part of the reservoir of functional AT1Rs.

PMID- 25995316
TI  - Fetal Mammalian Heart Generates a Robust Compensatory Response to Cell Loss.
AB  - BACKGROUND: Heart development is tightly regulated by signaling events acting on
      a defined number of progenitor and differentiated cardiac cells. Although loss of
      function of these signaling pathways leads to congenital malformation, the
      consequences of cardiac progenitor cell or embryonic cardiomyocyte loss are less
      clear. In this study, we tested the hypothesis that embryonic mouse hearts
      exhibit a robust mechanism for regeneration after extensive cell loss. METHODS
      AND RESULTS: By combining a conditional cell ablation approach with a novel
      blastocyst complementation strategy, we generated murine embryos that exhibit a
      full spectrum of cardiac progenitor cell or cardiomyocyte ablation. Remarkably,
      ablation of up to 60% of cardiac progenitor cells at embryonic day 7.5 was well
      tolerated and permitted embryo survival. Ablation of embryonic cardiomyocytes to
      a similar degree (50% to 60%) at embryonic day 9.0 could be fully rescued by
      residual myocytes with no obvious adult cardiac functional deficit. In both
      ablation models, an increase in cardiomyocyte proliferation rate was detected and
      accounted for at least some of the rapid recovery of myocardial cellularity and
      heart size. CONCLUSION: Our study defines the threshold for cell loss in the
      embryonic mammalian heart and reveals a robust cardiomyocyte compensatory
      response that sustains normal fetal development.

PMID- 25995317
TI  - Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke
      Prevention in Atrial Fibrillation and Secondary Prevention of Venous
      Thromboembolism: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Evidence regarding the use of direct oral anticoagulants (DOACs) in
      the elderly, particularly bleeding risks, is unclear despite the presence of
      greater comorbidities, polypharmacy, and altered pharmacokinetics in this age
      group. METHODS AND RESULTS: We performed a systematic review and meta-analysis of
      randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for
      efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in
      elderly participants (aged >=75 years) treated for acute venous thromboembolism
      or stroke prevention in atrial fibrillation. Nineteen studies were eligible for
      inclusion, but only 11 reported data specifically for elderly participants. The
      efficacy in managing thrombotic risks for each DOAC was similar or superior to
      VKA in elderly patients. A nonsignificantly higher risk of major bleeding than
      with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence
      interval, 0.97-1.44) but not with the 110-mg dose. Significantly higher
      gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35-2.35) and
      dabigatran 110 mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than
      VKA for dabigatran 150 mg (0.43, 0.26-0.72) and dabigatran 110 mg (0.36, 0.22
      0.61) were also observed. A significantly lower major bleeding risk in comparison
      with VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60 mg (0.81, 0.67
      0.98), and 30 mg (0.46, 0.38-0.57), whereas rivaroxaban showed similar risks.
      CONCLUSIONS: DOACs demonstrated at least equal efficacy to VKA in managing
      thrombotic risks in the elderly, but bleeding patterns were distinct. In
      particular, dabigatran was associated with a higher risk of gastrointestinal
      bleeding than VKA. Insufficient published data for apixaban, edoxaban, and
      rivaroxaban indicate that further work is needed to clarify the bleeding risks of
      these DOACs in the elderly. SYSTEMATIC REVIEW REGISTRATION:
      http://www.crd.york.ac.uk/PROSPERO. Unique identifier: PROSPERO CRD42014007171/.

PMID- 25995319
TI  - Great Expectations: MicroRNA-30d and Cardiac Resynchronization Therapy.

PMID- 25995318
TI  - Pathogenesis of the Novel Autoimmune-Associated Long-QT Syndrome.
AB  - BACKGROUND: Emerging clinical evidence demonstrates high prevalence of QTc
      prolongation and complex ventricular arrhythmias in patients with anti-Ro
      antibody (anti-Ro Ab)-positive autoimmune diseases. We tested the hypothesis that
      anti-Ro Abs target the HERG (human ether-a-go-go-related gene) K(+) channel,
      which conducts the rapidly activating delayed K(+) current, IKr, thereby causing
      delayed repolarization seen as QT interval prolongation on the ECG. METHODS AND
      RESULTS: Anti-Ro Ab-positive sera, purified IgG, and affinity-purified anti-52kDa
      Ro Abs from patients with autoimmune diseases and QTc prolongation were tested on
      IKr using HEK293 cells expressing HERG channel and native cardiac myocytes.
      Electrophysiological and biochemical data demonstrate that anti-Ro Abs inhibit
      IKr to prolong action potential duration by directly binding to the HERG channel
      protein. The 52-kDa Ro antigen-immunized guinea pigs showed QTc prolongation on
      ECG after developing high titers of anti-Ro Abs, which inhibited native IKr and
      cross-reacted with guinea pig ERG channel. CONCLUSIONS: The data establish that
      anti-Ro Abs from patients with autoimmune diseases inhibit IKr by cross-reacting
      with the HERG channel likely at the pore region where homology between anti-52
      kDa Ro antigen and HERG channel is present. The animal model of autoimmune
      associated QTc prolongation is the first to provide strong evidence for a
      pathogenic role of anti-Ro Abs in the development of QTc prolongation. It is
      proposed that adult patients with anti-Ro Abs may benefit from routine ECG
      screening and that those with QTc prolongation should receive counseling about
      drugs that may increase the risk for life-threatening arrhythmias.

PMID- 25995320
TI  - Circulating MicroRNA-30d Is Associated With Response to Cardiac Resynchronization
      Therapy in Heart Failure and Regulates Cardiomyocyte Apoptosis: A Translational
      Pilot Study.
AB  - BACKGROUND: Biomarkers that predict response to cardiac resynchronization therapy
      (CRT) in heart failure patients with dyssynchrony (HFDYS) would be clinically
      important. Circulating extracellular microRNAs (miRNAs) have emerged as novel
      biomarkers that may also play important functional roles, but their relevance as
      markers for CRT response has not been examined. METHODS AND RESULTS:
      Comprehensive miRNA polymerase chain reaction arrays were used to assess baseline
      levels of 766 plasma miRNAs in patients undergoing clinically indicated CRT in an
      initial discovery set (n=12) with and without subsequent echocardiographic
      improvement at 6 months after CRT. Validation of candidate miRNAs in 61
      additional patients confirmed that baseline plasma miR-30d was associated with
      CRT response (defined as an increase in left ventricular ejection fraction
      >=10%). MiR-30d was enriched in coronary sinus blood and increased in late
      contracting myocardium in a canine model of HFDYS, indicating cardiac origin with
      maximal expression in areas of high mechanical stress. We examined the functional
      effects of miR-30d in cultured cardiomyocytes and determined that miR-30d is
      expressed in cardiomyocytes and released in vesicles in response to mechanical
      stress. Overexpression of miR-30d in cultured cardiomyocytes led to cardiomyocyte
      growth and protected against apoptosis by targeting the mitogen-associated kinase
      4, a downstream effector of tumor necrosis factor. In HFDYS patients, miR-30d
      plasma levels inversely correlated with high-sensitivity troponin T, a marker of
      myocardial necrosis. CONCLUSIONS: Baseline plasma miR-30d level is associated
      with response to CRT in HFDYS in this translational pilot study. MiR-30d increase
      in cardiomyocytes correlates with areas of increased wall stress in HFDYS and is
      protective against deleterious tumor necrosis factor signaling.

PMID- 25995321
TI  - Noribogaine reduces nicotine self-administration in rats.
AB  - Noribogaine, a polypharmacological drug with activities at opioid receptors,
      ionotropic nicotinic receptors, and serotonin reuptake transporters, has been
      investigated for treatment of substance abuse-related disorders. Smoking
      cessation has major benefits for both individuals and society, therefore the aim
      of this study was to evaluate the potential of noribogaine for use as a treatment
      for nicotine dependence. Adult male Sprague-Dawley rats were trained to self
      administer nicotine intravenous. After initial food pellet training, followed by
      26 sessions of nicotine self-administration training, the rats were administered
      noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or
      saline using a within-subject design with a Latin square test schedule.
      Noribogaine dose-dependently decreased nicotine self-administration by up to 64%
      of saline-treated rats' levels and was equi-effective to 1.7 mg/kg
      intraperitoneal varenicline. Noribogaine was less efficient at reducing food
      pellets self-administration than at nicotine self-administration, inhibiting the
      nondrug reinforcing effects of palatable pellets by 23% at the highest dose.
      These results suggest that noribogaine dose-dependently attenuates drug-taking
      behavior for nicotine, attenuates the reinforcing effects of nicotine and is
      comparable to varenicline power in that regard. The findings from the present
      study hold promise for a new therapy to aid smoking cessation. 

PMID- 25995323
TI  - Is laboratory medicine ready for the era of personalized medicine? A survey
      addressed to laboratory directors of hospitals/academic schools of medicine in
      Europe.
AB  - Developments in "-omics" are creating a paradigm shift in laboratory medicine
      leading to personalized medicine. This allows the increase in diagnostics and
      therapeutics focused on individuals rather than populations. In order to
      investigate whether laboratory medicine is ready to play a key role in the
      integration of personalized medicine in routine health care and set the state-of
      the-art knowledge about personalized medicine and laboratory medicine in Europe,
      a questionnaire was constructed under the auspices of the European Federation of
      Clinical Chemistry and Laboratory Medicine (EFLM) and the European Society of
      Pharmacogenomics and Personalised Therapy (ESPT). The answers of the
      participating laboratory medicine professionals indicate that they are aware that
      personalized medicine can represent a new and promising health model, and that
      laboratory medicine should play a key role in supporting the implementation of
      personalized medicine in the clinical setting. Participants think that the
      current organization of laboratory medicine needs additional/relevant
      implementations such as (i) new technological facilities in -omics; (ii)
      additional training for the current personnel focused on the new methodologies;
      (iii) incorporation in the laboratory of new competencies in data interpretation
      and counseling; and (iv) cooperation and collaboration among professionals of
      different disciplines to integrate information according to a personalized
      medicine approach.

PMID- 25995322
TI  - Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis:
      the placebo-controlled SEDUCE study.
AB  - OBJECTIVE: To assess the effect of sildenafil, a phosphodiesterase type 5
      inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). METHODS:
      Randomised, placebo-controlled study in patients with SSc to assess the effect of
      sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU
      healing. The primary end point was the time to healing for each DU. Time to
      healing was compared between groups using Cox models for clustered data (two
      sided tests, p=0.05). RESULTS: Intention-to-treat analysis involved 83 patients
      with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo
      group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to
      1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of
      sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28)
      (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was
      lower in the sildenafil group compared with the placebo group at week (W) 8
      (1.23+/-1.61 vs 1.79+/-2.40 p=0.04) and W12 (0.86+/-1.62 vs 1.51+/-2.68, p=0.01)
      resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12).
      CONCLUSIONS: The primary end point was not reached in intention-to-treat, partly
      because of an unexpectedly high healing rate in the placebo group. We found a
      significant decrease in the number of DUs in favour of sildenafil compared with
      placebo at W8 and W12, confirming a sildenafil benefit. TRIAL REGISTRATION
      NUMBER: NCT01295736.

PMID- 25995324
TI  - Mouse prenatal platelet-forming lineages share a core transcriptional program but
      divergent dependence on MPL.
AB  - The thrombopoietic environment of the neonate is established during prenatal
      life; therefore, a comprehensive understanding of platelet-forming cell
      development during embryogenesis is critical to understanding the etiology of
      early-onset thrombocytopenia. The recent discovery that the first platelet
      forming cells of the conceptus are not megakaryocytes (MKs) but diploid platelet
      forming cells (DPFCs) revealed a previously unappreciated complexity in
      thrombopoiesis. This raises important questions, including the following. When do
      conventional MKs appear? Do pathogenic genetic lesions of adult MKs affect DPFCs?
      What role does myeloproliferative leukemia virus (MPL), a key regulator of adult
      megakaryopoiesis, play in prenatal platelet-forming lineages? We performed a
      comprehensive study to determine the spatial and temporal appearance of prenatal
      platelet-forming lineages. We demonstrate that DPFCs originate in the yolk sac
      and then rapidly migrate to other extra- and intraembryonic tissues. Using gene
      disruption models of Gata1 and Nfe2, we demonstrate that perturbing essential
      adult MK genes causes an analogous phenotype in the early embryo before the onset
      of hematopoietic stem/progenitor cell-driven (definitive) hematopoiesis. Finally,
      we present the surprising finding that DPFC and MK commitment from their
      respective precursors is MPL independent in vivo but that completion of MK
      differentiation and establishment of the prenatal platelet mass is dependent on
      MPL expression. 

PMID- 25995325
TI  - Lymphedema Characteristics and the Efficacy of Complex Decongestive Physiotherapy
      in Malignant Lymphedema.
AB  - The aim of this study is to identify the lymphedema characteristics and the
      efficacy of complex decongestive physiotherapy (CDP) in 29 patients with
      malignant lymphedema. After CDP, total decreased volume of lymphedema was 306 mL,
      percentage of excess volume (PEV) changed from 43.4% to 22.7%, and lymphedema
      severity improved from severe to moderate status. The CDP efficacy-percentage
      reduction in excess volume (PREV) was 46.6%. The stage of lymphedema (P = .004),
      range of motion (P < .001), pain, heaviness, and tension scores (P < .001) were
      significantly improved after CDP. This shows that CDP is efficacious and useful
      in malignant lymphedema. 

PMID- 25995326
TI  - MAOHUZI6/ETHYLENE INSENSITIVE3-LIKE1 and ETHYLENE INSENSITIVE3-LIKE2 Regulate
      Ethylene Response of Roots and Coleoptiles and Negatively Affect Salt Tolerance
      in Rice.
AB  - Ethylene plays important roles in plant growth, development, and stress
      responses. The ethylene signaling pathway has been studied extensively, mainly in
      Arabidopsis (Arabidopsis thaliana). However, the molecular mechanism of ethylene
      signaling is largely unknown in rice (Oryza sativa). Previously, we have isolated
      a set of rice ethylene-response mutants. Here, we characterized the mutant
      maohuzi6 (mhz6). Through map-based cloning, we found that MHZ6 encodes ETHYLENE
      INSENSITIVE3-LIKE1 (OsEIL1), a rice homolog of ETHYLENE INSENSITIVE3 (EIN3),
      which is the master transcriptional regulator of ethylene signaling in
      Arabidopsis. Disruption of MHZ6/OsEIL1 caused ethylene insensitivity mainly in
      roots, whereas silencing of the closely related OsEIL2 led to ethylene
      insensitivity mainly in coleoptiles of etiolated seedlings. This organ-specific
      functional divergence is different from the functional features of EIN3 and EIL1,
      both of which mediate the incomplete ethylene responses of Arabidopsis etiolated
      seedlings. In Arabidopsis, EIN3 and EIL1 play positive roles in plant salt
      tolerance. In rice, however, lack of MHZ6/OsEIL1 or OsEIL2 functions improves
      salt tolerance, whereas the overexpressing lines exhibit salt hypersensitivity at
      the seedling stage, indicating that MHZ6/OsEIL1 and OsEIL2 negatively regulate
      salt tolerance in rice. Furthermore, this negative regulation by MHZ6/OsEIL1 and
      OsEIL2 in salt tolerance is likely attributable in part to the direct regulation
      of HIGH-AFFINITY K(+) TRANSPORTER2;1 expression and Na(+) uptake in roots.
      Additionally, MHZ6/OsEIL1 overexpression promotes grain size and thousand-grain
      weight. Together, our study provides insights for the functional diversification
      of MHZ6/OsEIL1 and OsEIL2 in ethylene response and finds a novel mode of ethylene
      regulated salt stress response that could be helpful for engineering salt
      tolerant crops. 

PMID- 25995328
TI  - Neural plasticity and memory: molecular mechanism.
AB  - Deciphering the cellular and molecular mechanisms of memory has been an important
      topic encompassing the learning and memory domain besides the neurodegenerative
      disorders. Synapses accumulate cognitive information from life-lasting
      alterations of their molecular and structural composition. Current memory storage
      models identify posttranslational modification imperative for short-term
      information storage and mRNA translation for long-term information storage.
      However, the precise account of these modifications has not been summarized at
      the individual synapse level. Therefore, herein we describe the spatiotemporal
      reorganization of synaptic plasticity at the dendritic spine level to elucidate
      the mechanism through which synaptic substructures are remodeled; though at the
      molecular level, such mechanisms are still quite unclear. It has thus been
      concluded that the existing mechanisms do not entirely elaborate memory storage
      processes. Further efforts are therefore encouraged to delineate the mechanism of
      neuronal connectivity at the chemical level as well, including inter- or
      intramolecular bonding patterns at the synaptic level, which may be a permissive
      and vital step of memory storage. 

PMID- 25995327
TI  - The ETHYLENE RESPONSE FACTORs ERF6 and ERF11 Antagonistically Regulate Mannitol
      Induced Growth Inhibition in Arabidopsis.
AB  - Leaf growth is a tightly regulated and complex process, which responds in a
      dynamic manner to changing environmental conditions, but the mechanisms that
      reduce growth under adverse conditions are rather poorly understood. We
      previously identified a growth inhibitory pathway regulating leaf growth upon
      exposure to a low concentration of mannitol and characterized the ETHYLENE
      RESPONSE FACTOR (ERF)/APETALA2 transcription factor ERF6 as a central activator
      of both leaf growth inhibition and induction of stress tolerance genes. Here, we
      describe the role of the transcriptional repressor ERF11 in relation to the ERF6
      mediated stress response in Arabidopsis (Arabidopsis thaliana). Using inducible
      overexpression lines, we show that ERF6 induces the expression of ERF11. ERF11 in
      turn molecularly counteracts the action of ERF6 and represses at least some of
      the ERF6-induced genes by directly competing for the target gene promoters. As a
      phenotypical consequence of the ERF6-ERF11 antagonism, the extreme dwarfism
      caused by ERF6 overexpression is suppressed by overexpression of ERF11. Together,
      our data demonstrate that dynamic mechanisms exist to fine-tune the stress
      response and that ERF11 counteracts ERF6 to maintain a balance between plant
      growth and stress defense. 

PMID- 25995329
TI  - Recommendations on the use of echocardiography in adult hypertension: a report
      from the European Association of Cardiovascular Imaging (EACVI) and the American
      Society of Echocardiography (ASE)?.
AB  - Hypertension remains a major contributor to the global burden of disease. The
      measurement of blood pressure continues to have pitfalls related to both
      physiological aspects and acute variation. As the left ventricle (LV) remains one
      of the main target organs of hypertension, and echocardiographic measures of
      structure and function carry prognostic information in this setting, the
      development of a consensus position on the use of echocardiography in this
      setting is important. Recent developments in the assessment of LV hypertrophy and
      LV systolic and diastolic function have prompted the preparation of this
      document. The focus of this work is on the cardiovascular responses to
      hypertension rather than the diagnosis of secondary hypertension. Sections
      address the pathophysiology of the cardiac and vascular responses to
      hypertension, measurement of LV mass, geometry, and function, as well as effects
      of treatment. 

PMID- 25995330
TI  - An additional genus and two additional species of Forticulcitinae (Digenea:
      Haploporidae).
AB  - Forticulcita platana sp. n. and Forticulcita apiensis sp. n. are described from
      Mugil liza Valenciennes in Argentina, and from Mugil cephalus Linnaeus in Salt
      Springs, Florida, USA, respectively. Supplemental material relating to the
      hermaphroditic sac of Forticulcita gibsoni Blasco-Costa, Montero, Balbuena, Raga
      et Kostadinova, 2009 is provided from a specimen isolated from M. cephalus off
      Crete, Greece. Forticulcita platana can be distinguished from all species of
      Forticulcita Overstreet, 1982 except F. gibsoni, based on possessing small pads
      or gland cells along the hermaphroditic duct. It can be differentiated from that
      species in possessing a hermaphroditic sac that is one and a half to two times
      longer than wide rather than one that is approximately three times longer than
      wide, longer eggs (44-52 MUm rather than 34-44 MUm long) and a shorter post
      testicular space (< 45% of the body length). Forticulcita apiensis can be
      differentiated from the other species of Forticulcita in possessing a testis that
      is shorter than or equal to the pharynx rather than one that is longer than the
      pharynx. Xiha gen. n. is erected for Dicrogaster fastigatus Thatcher et Sparks,
      1958 as Xiha fastigata (Thatcher et Sparks, 1958) comb. n., and we tentatively
      consider Dicrogaster fragilis Fernandez Bargiela, 1987 to be Xiha fragilis
      (Fernandez Bargiela, 1987) comb. n. The new genus fits within the concept of
      Forticulcitinae Blasco-Costa, Balbuena, Kostadinova et Olson, 2009 in having a
      vitellarium comprised of a single elongate to subspherical mass. Xiha can be
      differentiated from Forticulcita in having spines lining the hermaphroditic duct,
      or intromittent organ. A Bayesian inference analysis of partial 28S rDNA
      sequences of the two New World species of Forticulcita, Xiha fastigata and
      previously published haploporids places Xiha fastigata within the Forticulcitinae
      and sister to Forticulcita. Amended diagnoses for the subfamily and for
      Dicrogaster Looss, 1902 are provided. 

PMID- 25995331
TI  - Electronic consultations (e-consults) to improve access to specialty care: a
      systematic review and narrative synthesis.
AB  - BACKGROUND: We define electronic consultations ("e-consults") as asynchronous,
      consultative, provider-to-provider communications within a shared electronic
      health record (EHR) or web-based platform. E-consults are intended to improve
      access to specialty expertise for patients and providers without the need for a
      face-to-face visit. Our goal was to systematically review and summarize the
      literature describing the use and effects of e-consults. METHODS: We searched
      PubMed, EMBASE, the Cochrane Library, and CINAHL for studies related to e
      consults published between 1990 through December 2014. Three reviewers identified
      empirical studies and system descriptions, including articles on systems that
      used a shared EHR or web-based platform, connected providers in the same health
      system, were used for two-way provider communication, and were text-based.
      RESULTS: Our final review included 27 articles. Twenty-two were research studies
      and five were system descriptions. Eighteen originated from one of three sites
      with well-developed e-consult programs. Most studies reported on workflow impact,
      timeliness of specialty input, and/or provider perceptions of e-consults. E
      consultations are used in a variety of ways within and across medical centers.
      They provide timely access to specialty care and are well-received by primary
      care providers. DISCUSSION: E-consults are feasible in a variety of settings,
      flexible in their application, and facilitate timely specialty advice. More
      extensive and rigorous studies are needed to inform the e-consult process and
      describe its effect on access to specialty visits, cost and clinical outcomes.

PMID- 25995332
TI  - Use of a Tablet-Based Risk Assessment Program to Improve Health Counseling and
      Patient-Provider Relationships in a Federally Qualified Health Center.
AB  - This study evaluates the impact of an interactive, tablet-based lifestyle
      behavior questionnaire prior to a patient's primary care visit on counseling for
      health behaviors and patient-provider relationships. Using a quasi-experimental
      design at 2 federally qualified health centers, adults aged 18 to 35 years were
      asked to complete a tablet-based assessment about nutrition, physical activity,
      weight, smoking status, and alcohol use to identify unhealthy behaviors and their
      desire to discuss them with their provider. In the intervention group,
      participants were more likely to trust their providers (83% vs 71%, P = .0427)
      and feel that their provider cared about their health (80% vs 68%, P = .0468).
      Overweight/obese individuals were more likely to discuss weight loss with their
      doctor (59% vs 33%, P = .0088). Integrating information technology into primary
      care to encourage providers to discuss lifestyle issues and promote a positive
      patient-provider relationship may help improve the health promotion in primary
      care practices.

PMID- 25995333
TI  - Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.
AB  - OBJECTIVE: To explore the efficacy of local oxytocin for the treatment of post
      menopausal vaginal atrophy. DESIGN: Double-blinded randomised controlled trial.
      SETTING: Healthy post-menopausal women in Stockholm, Sweden. PARTICIPANTS: Sixty
      four post-menopausal women between February and June 2012 at the Karolinska
      University Hospital Huddinge/Sweden. MAIN OUTCOME MEASURES: The efficacy of
      oxytocin for treatment of vaginal atrophy after seven weeks and cytological
      evaluation. RESULTS: The percentage of superficial cells in the vaginal smears
      and the maturation values were significantly increased after seven weeks of
      treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The
      vaginal pH decreased significantly after seven weeks of treatment with vagitocin
      100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological
      evaluation, were significantly reduced after administration of vagitocin 100 IU
      (p = 0.03). The thickness of the endometrium did not differ between the treatment
      and placebo groups after seven weeks of treatment. The symptom experienced as the
      most bothersome was significantly reduced after seven weeks of treatment in the
      women receiving vagitocin 400 IU compared to women in the placebo group (p =
      0.0089). CONCLUSIONS: Treatment with intravaginally applied oxytocin could be an
      alternative to local estrogen treatment in women with post-menopausal vaginal
      atrophy.

PMID- 25995334
TI  - Autoimmune hepatitis: an approach to disease understanding and management.
AB  - INTRODUCTION: Autoimmune hepatitis is a chronic immune-mediated liver injury,
      frequently associated with progression to end-stage liver disease if untreated.
      Patients commonly present with hepatitis, positive immune serology, elevated
      immunoglobulins and compatible liver histology, in the absence of an alternative
      aetiology. SOURCES OF DATA: Data for this review were obtained using PubMed.
      AREAS OF AGREEMENT: Disease usually responds to steroids and azathioprine, and
      appears to be a manifestation of autoimmune predisposition triggered in
      genetically susceptible individuals exposed to likely environmental challenges.
      We provide an up-to-date approach to disease understanding and management along
      with the clinical approach to diagnosis and current treatment suggestions. AREAS
      OF CONTROVERSY: Controversies such as second line therapies and novel markers of
      disease activity are introduced. GROWING POINTS: Increased understanding of the
      immunoregulatory mechanisms behind autoimmune hepatitis has led to opportunities
      for new therapies. These are developed including a discussion of timely research
      studies relevant to future therapies for patients.

PMID- 25995335
TI  - Diagnosing orthostatic hypotension: a narrative review of the evidence.
AB  - BACKGROUND: Orthostatic hypotension (OH) is very common, particularly in older
      populations. Diagnostic criteria exist but appear to be arbitrary rather than
      evidence based. This review will visit the evidence for diagnostic strategies for
      OH. DATA SOURCES: Medline (OvidSP), EMBASE (OvidSP), ISI Web of Science, the
      Health Technology Assessments Database and the Cochrane Library. AREAS OF
      AGREEMENT: A 5-min rest is required before measuring baseline. An active stand
      with continuous blood pressure (BP) monitoring is preferable to a tilt test to
      identify initial OH in particular. At least 2 min in the upright position is
      required. A systolic drop of 20 or a diastolic drop of 10 is supported by the
      evidence. Reproducibility when testing for OH is poor. AREAS OF CONTROVERSY: Is
      the active stand preferable to the tilt test to diagnose classical OH? Although
      continuous BP monitoring increases diagnostic rates, does it improve clinical
      outcomes? Should symptoms be used to inform diagnosis? AREAS TIMELY FOR RESEARCH:
      Establishing the long-term clinical outcomes for transient drops in BP detected
      on continuous, non-invasive monitoring. Evaluating the different patterns of BP
      drop to aid diagnosis and direct treatment.

PMID- 25995338
TI  - Neutrophil-Lymphocyte Ratio in Behcet Disease.

PMID- 25995336
TI  - Haemophilus influenzae responds to glucocorticoids used in asthma therapy by
      modulation of biofilm formation and antibiotic resistance.
AB  - Glucocorticosteroids are used as a main treatment to reduce airway inflammation
      in people with asthma who suffer from neutrophilic airway inflammation, a
      condition frequently associated with Haemophilus influenzae colonization. Here we
      show that glucocorticosteroids have a direct influence on the behavior of H.
      influenzae that may account for associated difficulties with therapy. Using a
      mouse model of infection, we show that corticosteroid treatment promotes H.
      influenzae persistence. Transcriptomic analysis of bacteria either isolated from
      infected mouse airway or grown in laboratory medium identified a number of genes
      encoding regulatory factors whose expression responded to the presence of
      glucocorticosteroids. Importantly, a number of these corticosteroid-responsive
      genes also showed elevated expression in H. influenzae within sputum from asthma
      patients undergoing steroid treatment. Addition of corticosteroid to H.
      influenzae led to alteration in biofilm formation and enhanced resistance to
      azithromycin, and promoted azithromycin resistance in an animal model of
      respiratory infection. Taken together, these data strongly suggest that H.
      influenzae can respond directly to corticosteroid treatment in the airway
      potentially influencing biofilm formation, persistence and the efficacy of
      antibiotic treatment. 

PMID- 25995337
TI  - Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating
      TNFR1.
AB  - TNF is a central actor during inflammation and a well-recognized drug target for
      inflammatory diseases. We found that the mouse strain SPRET/Ei, known for extreme
      and dominant resistance against TNF-induced shock, displays weak expression of
      TNF receptor 1 protein (TNFR1) but normal mRNA expression, a trait genetically
      linked to the major TNFR1 coding gene Tnfrsf1a and to a locus harbouring the
      predicted TNFR1-regulating miR-511. This miRNA is a genuine TNFR1 regulator in
      cells. In mice, overexpression of miR-511 down-regulates TNFR1 and protects
      against TNF, while anti-miR-511 up-regulates TNFR1 and sensitizes for TNF,
      breaking the resistance of SPRET/Ei. We found that miR-511 inhibits endotoxemia
      and experimental hepatitis and that this miR is strongly induced by
      glucocorticoids and is a true TNFR1 modulator and thus an anti-inflammatory miR.
      Since minimal reductions of TNFR1 have considerable effects on TNF sensitivity,
      we believe that at least part of the anti-inflammatory effects of glucocorti
      coids are mediated by induction of this miR, resulting in reduced TNFR1
      expression. 

PMID- 25995339
TI  - Growth Factor Receptor Fusions Predict Therapeutic Sensitivity.
AB  - Dysregulated growth factor pathways promote tumor growth in many cancers, but
      receptor-targeting strategies frequently offer limited benefit despite activation
      by receptor overexpression or amplification. In contrast, tumors harboring growth
      factor receptor fusions display exquisite dependence on receptor activity,
      providing predictive markers for patient response to inform precise oncology
      treatment.

PMID- 25995340
TI  - Obesity, Intrapancreatic Fatty Infiltration, and Pancreatic Cancer.
AB  - Obesity and intrapancreatic fatty infiltration are associated with increased risk
      of pancreatic cancer and its precursor lesions. The interplay among obesity,
      inflammation, and oncogenic Kras signaling promotes pancreatic tumorigenesis.
      Targeting the interaction between obesity-associated inflammation and Kras
      signaling may provide new strategies for prevention and therapy of pancreatic
      cancer.

PMID- 25995341
TI  - Model Matters: Differences in Orthotopic Rat Hepatocellular Carcinoma Physiology
      Determine Therapy Response to Sorafenib.
AB  - PURPOSE: Preclinical model systems should faithfully reflect the complexity of
      the human pathology. In hepatocellular carcinoma (HCC), the tumor vasculature is
      of particular interest in diagnosis and therapy. By comparing two commonly
      applied preclinical model systems, diethylnitrosamine induced (DEN) and
      orthotopically implanted (McA) rat HCC, we aimed to measure tumor biology
      noninvasively and identify differences between the models. EXPERIMENTAL DESIGN:
      DEN and McA tumor development was monitored by MRI and PET. A slice-based
      correlation of imaging and histopathology was performed. Array CGH analyses were
      applied to determine genetic heterogeneity. Therapy response to sorafenib was
      tested in DEN and McA tumors. RESULTS: Histologically and biochemically confirmed
      liver damage resulted in increased (18)F-fluorodeoxyglucose (FDG) PET uptake and
      perfusion in DEN animals only. DEN tumors exhibited G1-3 grading compared with
      uniform G3 grading of McA tumors. Array comparative genomic hybridization
      revealed a highly variable chromosomal aberration pattern in DEN tumors.
      Heterogeneity of DEN tumors was reflected in more variable imaging parameter
      values. DEN tumors exhibited lower mean growth rates and FDG uptake and higher
      diffusion and perfusion values compared with McA tumors. To test the significance
      of these differences, the multikinase inhibitor sorafenib was administered,
      resulting in reduced volume growth kinetics and perfusion in the DEN group only.
      CONCLUSIONS: This work depicts the feasibility and importance of in depth
      preclinical tumor model characterization and suggests the DEN model as a
      promising model system of multifocal nodular HCC in future therapy studies.

PMID- 25995342
TI  - Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel
      Resistance in Advanced Prostate Cancer.
AB  - PURPOSE: Previous studies show that inhibition of ABCB1 expression overcomes
      acquired docetaxel resistance in C4-2B-TaxR cells. In this study, we examined
      whether antiandrogens, such as bicalutamide and enzalutamide, could inhibit ABCB1
      activity and overcome resistance to docetaxel. EXPERIMENTAL DESIGN: ABCB1 efflux
      activity was determined using a rhodamine efflux assay. ABCB1 ATPase activity was
      determined by Pgp-Glo assay systems. The effects of the antiandrogens
      bicalutamide and enzalutamide on docetaxel sensitivity were determined by cell
      growth assays and tumor growth in vivo. RESULTS: We found that bicalutamide and
      enzalutamide inhibit ABCB1 ATP-binding cassette transporter activity through
      blocking ABCB1 efflux activity. Bicalutamide inhibited ABCB1 efflux activity by
      40%, whereas enzalutamide inhibited ABCB1 efflux activity by approximately 60%.
      Both bicalutamide and enzalutamide inhibit ABCB1 ATPase activity. In addition,
      bicalutamide and enzalutamide inhibit ABCB1 efflux activity and desensitize
      docetaxel-resistant and androgen receptor (AR)-negative DU145 cells. Combination
      of bicalutamide with docetaxel had a significant antitumor effect in both AR
      positive and AR-negative docetaxel-resistant xenograft models, suggesting that
      bicalutamide desensitizes docetaxel-resistant cells to docetaxel treatment
      independent of AR status. CONCLUSIONS: We identified a novel mechanism of action
      for antiandrogens such as bicalutamide and enzalutamide as inhibitors of ABCB1
      efflux and ATPase activity. Bicalutamide and enzalutamide desensitize docetaxel
      resistant prostate cancer cells to docetaxel treatment independent of AR status.
      These studies may lead to the development of combinational therapies with
      bicalutamide/enzalutamide and docetaxel as effective regimens to treat advanced
      prostate cancer independent of AR status, and possibly other types of cancer.

PMID- 25995343
TI  - The genetics of Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) was previously described as the prototypical
      sporadic disease; however, rapid advances in population and molecular genetics
      have revealed the existence of a significant number genetic risk factors,
      prompting its redefinition as a primarily genetic disorder. SOURCES OF DATA: Data
      for this review have been gathered from the published literature. AREAS OF
      AGREEMENT: Multiple haplotypes conveying variable but quantifiable genetic risk,
      acting concurrently and possibly interacting with one another, provide the basis
      for a new model of PD. The beginning of this revolution in our understanding came
      from the clinical observation of parkinsonism with a Mendelian pattern of
      inheritance in a number of families. The functional work that followed elucidated
      multiple disease pathways leading to the degeneration of the substantia nigra
      that characterizes PD. It is however only in recent years, with the emergence of
      large cohort genome-wide association studies (GWAS), that the relevance of these
      pathways to so-called sporadic PD has become apparent. AREAS OF CONTROVERSY: A
      substantial portion of the presumed genetic inheritance of PD remains at present
      undefined. Although it is likely that so-called intermediate risk genetic risk
      factors are the principal component of this 'missing heritability', this is yet
      to be proved. GROWING POINTS: Although the picture is by now means complete, the
      beginnings of rational basis for genetic screening of PD risk have begun to
      emerge. Equally, this enhanced understanding of the various genetic and in turn
      biochemical pathways shows promising signs of producing fruitful therapeutic
      strategies. Technological advances promise to reduce the costs associated with
      and further increase our capability to understand the complex influence of
      genetics on the pathogenesis of PD. AREAS TIMELY FOR DEVELOPING RESEARCH: The
      coming years will require the enhancement of current techniques and the
      development of new ones to define PD's missing heritability. It will also require
      functional work to define better and in turn potentially reverse the mechanisms
      that contribute with large effect sizes to the risk of sporadic PD.

PMID- 25995344
TI  - Different target-discrimination times can be followed by the same saccade
      initiation timing in different stimulus conditions during visual searches.
AB  - The neuronal processes that underlie visual searches can be divided into two
      stages: target discrimination and saccade preparation/generation. This predicts
      that the length of time of the prediscrimination stage varies according to the
      search difficulty across different stimulus conditions, whereas the length of the
      latter postdiscrimination stage is stimulus invariant. However, recent studies
      have suggested that the length of the postdiscrimination interval changes with
      different stimulus conditions. To address whether and how the visual stimulus
      affects determination of the postdiscrimination interval, we recorded single
      neuron activity in the lateral intraparietal area (LIP) when monkeys (Macaca
      fuscata) performed a color-singleton search involving four stimulus conditions
      that differed regarding luminance (Bright vs. Dim) and target-distractor color
      similarity (Easy vs. Difficult). We specifically focused on comparing activities
      between the Bright-Difficult and Dim-Easy conditions, in which the visual stimuli
      were considerably different, but the mean reaction times were indistinguishable.
      This allowed us to examine the neuronal activity when the difference in the
      degree of search speed between different stimulus conditions was minimal. We
      found that not only prediscrimination but also postdiscrimination intervals
      varied across stimulus conditions: the postdiscrimination interval was longer in
      the Dim-Easy condition than in the Bright-Difficult condition. Further analysis
      revealed that the postdiscrimination interval might vary with stimulus luminance.
      A computer simulation using an accumulation-to-threshold model suggested that the
      luminance-related difference in visual response strength at discrimination time
      could be the cause of different postdiscrimination intervals. 

PMID- 25995345
TI  - Brain stem activity changes associated with restored sympathetic drive following
      CPAP treatment in OSA subjects: a longitudinal investigation.
AB  - Obstructive sleep apnea (OSA) is associated with significantly elevated muscle
      sympathetic nerve activity (MSNA), leading to hypertension and increased
      cardiovascular morbidity. Although little is known about the mechanisms
      responsible for the sympathoexcitation, we have recently shown that the elevated
      MSNA in OSA is associated with altered neural processing in various brain stem
      sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary
      raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to
      determine if treatment of OSA with continuous positive airway pressure (CPAP)
      would reduce the elevated MSNA and reverse the brain stem functional changes
      associated with the elevated MSNA. We performed concurrent recordings of MSNA and
      blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using
      high-resolution functional magnetic resonance imaging, in 15 controls and 13
      subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of
      CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 +/- 4 to
      23 +/- 3 bursts/min and from 77 +/- 7 to 36 +/- 3 bursts/100 heart beats.
      Importantly, we found that MSNA-coupled changes in BOLD signal intensity within
      the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla
      returned to control levels. That is, CPAP treatment completely reversed brain
      stem functional changes associated with elevated MSNA in untreated OSA subjects.
      These data highlight the effectiveness of CPAP treatment in reducing one of the
      most significant health issues associated with OSA, that is, elevated MSNA and
      its associated elevated morbidity. 

PMID- 25995346
TI  - A hard-wired priority map in the superior colliculus shaped by asymmetric
      inhibitory circuitry.
AB  - The mammalian superior colliculus (SC) is a laminar midbrain structure that
      translates visual signals into commands to shift the focus of attention and gaze.
      The SC plays an integral role in selecting targets and ultimately generating
      rapid eye movements to those targets. In all mammals studied to date, neurons in
      the SC are arranged topographically such that the location of visual stimuli and
      the endpoints of orienting movements form organized maps in superficial and
      deeper layers, respectively. The organization of these maps is thought to
      underlie attentional priority by assessing which regions of the visual field
      contain behaviorally relevant information. Using voltage imaging and patch-clamp
      recordings in parasagittal SC slices from the rat, we found the synaptic
      circuitry of the visuosensory map in the SC imposes a strong bias. Voltage
      imaging of responses to electrical stimulation revealed more spread in the caudal
      direction than the rostral direction. Pharmacological experiments demonstrated
      that this asymmetry arises from GABAA receptor activation rostral to the site of
      stimulation. Patch-clamp recordings confirmed this rostrally directed inhibitory
      circuit and showed that it is contained within the visuosensory layers of the SC.
      Stimulation of two sites showed that initial stimulation of a caudal site can
      take priority over subsequent stimulation of a rostral site. Taken together, our
      data indicate that the circuitry of the visuosensory SC is hard-wired to give
      higher priority to more peripheral targets, and this property is conferred by a
      uniquely structured, dedicated inhibitory circuit.

PMID- 25995347
TI  - Diabetes induces GABA receptor plasticity in murine vagal motor neurons.
AB  - Autonomic dysregulation accompanies type-1 diabetes, and synaptic regulation of
      parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the
      vagus (DMV) is altered after chronic hyperglycemia/hypoinsulinemia. Tonic gamma
      aminobutyric acid A (GABAA) inhibition prominently regulates DMV neuron activity,
      which contributes to autonomic control of energy homeostasis. This study
      investigated persistent effects of chronic hyperglycemia/hypoinsulinemia on GABAA
      receptor-mediated inhibition in the DMV after streptozotocin-induced type-1
      diabetes using electrophysiological recordings in vitro, quantitative (q)RT-PCR,
      and immunohistochemistry. Application of the nonspecific GABAA receptor agonist
      muscimol evoked an outward current of significantly larger amplitude in DMV
      neurons from diabetic mice than controls. Results from application of 4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP), a delta-subunit
      agonist, suggested that GABAA receptors containing delta-subunits contributed to
      the enhanced inducible tonic GABA current in diabetic mice. Sensitivity to THIP
      of inhibitory postsynaptic currents in DMV neurons from diabetic mice was also
      increased. Results from qRT-PCR and immunohistochemical analyses indicated that
      the altered GABAergic inhibition may be related to increased trafficking of GABAA
      receptors that contain the delta-subunit, rather than an expression change.
      Overall these findings suggest increased sensitivity of delta-subunit containing
      GABAA receptors after several days of hyperglycemia/hypoinsulinemia, which
      dramatically alters GABAergic inhibition of DMV neurons and could contribute to
      diabetic autonomic dysregulation. 

PMID- 25995348
TI  - Posttetanic enhancement of striato-pallidal synaptic transmission.
AB  - The striato (Str)-globus pallidus external segment (GPe) projection plays major
      roles in the control of neuronal activity in the basal ganglia under both normal
      and pathological conditions. The present study used rat brain slice preparations
      to characterize the enhancement of Str-GPe synapses observed after repetitive
      conditioning stimuli (CS) of Str with the whole cell patch-clamp recording
      technique. The results show that 1) the Str-GPe synapses have a posttetanic
      enhancement (PTE) mechanism, which is considered to be a combination of an
      augmentation and a posttetanic potentiation; 2) the degree of PTE observed in GPe
      neurons had a wide range and was positively correlated with a wide range of
      paired-pulse ratios assessed before application of CS; 3) a wide range of CS,
      from frequencies as low as 2 Hz with as few as 5 pulses to as high as 100 Hz with
      100 pulses, could induce PTE; 4) the decay time constant of PTE was dependent on
      the strength of CS and was prolonged greatly, up to 120 s, when strong CS were
      applied; and 5) the level of postsynaptic Cl(-) became a limiting factor for the
      degree of PTE when strong CS were applied. These results imply that Str-GPe
      synapses transmit inhibitions in a nonlinear activity-weighted manner, which may
      be suited for scaling timing and force of repeated or sequential body movements.
      Other possible factors controlling the induction of PTE and functional
      implications are also discussed. 

PMID- 25995349
TI  - Changes in visual and sensory-motor resting-state functional connectivity support
      motor learning by observing.
AB  - Motor learning occurs not only through direct first-hand experience but also
      through observation (Mattar AA, Gribble PL. Neuron 46: 153-160, 2005). When
      observing the actions of others, we activate many of the same brain regions
      involved in performing those actions ourselves (Malfait N, Valyear KF, Culham JC,
      Anton JL, Brown LE, Gribble PL. J Cogn Neurosci 22: 1493-1503, 2010). Links
      between neural systems for vision and action have been reported in
      neurophysiological (Strafella AP, Paus T. Neuroreport 11: 2289-2292, 2000;
      Watkins KE, Strafella AP, Paus T. Neuropsychologia 41: 989-994, 2003), brain
      imaging (Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz
      RJ, Zilles K, Rizzolatti G, Freund HJ. Eur J Neurosci 13: 400-404, 2001; Iacoboni
      M, Woods RP, Brass M, Bekkering H, Mazziotta JC, Rizzolatti G. Science 286: 2526
      2528, 1999), and eye tracking (Flanagan JR, Johansson RS. Nature 424: 769-771,
      2003) studies. Here we used a force field learning paradigm coupled with resting
      state fMRI to investigate the brain areas involved in motor learning by
      observing. We examined changes in resting-state functional connectivity (FC)
      after an observational learning task and found a network consisting of V5/MT,
      cerebellum, and primary motor and somatosensory cortices in which changes in FC
      were correlated with the amount of motor learning achieved through observation,
      as assessed behaviorally after resting-state fMRI scans. The observed FC changes
      in this network are not due to visual attention to motion or observation of
      movement errors but rather are specifically linked to motor learning. These
      results support the idea that brain networks linking action observation and motor
      control also facilitate motor learning. 

PMID- 25995350
TI  - Value-based attentional capture influences context-dependent decision-making.
AB  - Normative theories posit that value-based decision-making is context independent.
      However, decisions between two high-value options can be suboptimally biased by
      the introduction of a third low-value option. This context-dependent modulation
      is consistent with the divisive normalization of the value of each stimulus by
      the total value of all stimuli. In addition, an independent line of research
      demonstrates that pairing a stimulus with a high-value outcome can lead to
      attentional capture that can mediate the efficiency of visual information
      processing. Here we tested the hypothesis that value-based attentional capture
      interacts with value-based normalization to influence the optimality of decision
      making. We used a binary-choice paradigm in which observers selected between two
      targets and the color of each target indicated the magnitude of their reward
      potential. Observers also had to simultaneously ignore a task-irrelevant
      distractor rendered in a color that was previously associated with a specific
      reward magnitude. When the color of the task-irrelevant distractor was previously
      associated with a high reward, observers responded more slowly and less
      optimally. Moreover, as the learned value of the distractor increased,
      electrophysiological data revealed an attenuation of the lateralized N1 and N2Pc
      responses evoked by the relevant choice stimuli and an attenuation of the late
      positive deflection (LPD). Collectively, these behavioral and
      electrophysiological data suggest that value-based attentional capture and value
      based normalization jointly mediate the influence of context on free-choice
      decision-making. 

PMID- 25995351
TI  - Ambient illumination switches contrast preference of specific retinal processing
      streams.
AB  - Contrast, a fundamental feature of visual scenes, is encoded in a distributed
      manner by ~ 20 retinal ganglion cell (RGC) types, which stream visual information
      to the brain. RGC types respond preferentially to positive (ON(pref)) or negative
      (OFF(pref)) contrast and differ in their sensitivity to preferred contrast and
      responsiveness to nonpreferred stimuli. Vision operates over an enormous range of
      mean light levels. The influence of ambient illumination on contrast encoding
      across RGC types is not well understood. Here, we used large-scale multielectrode
      array recordings to characterize responses of mouse RGCs under lighting
      conditions spanning five orders in brightness magnitude. We identify three
      functional RGC types that switch contrast preference in a luminance-dependent
      manner (Sw1-, Sw2-, and Sw3-RGCs). As ambient illumination increases, Sw1- and
      Sw2-RGCs shift from ON(pref) to OFF(pref) and Sw3-RGCs from OFF(pref) to
      ON(pref). In all cases, transitions in contrast preference are reversible and
      track light levels. By mapping spatiotemporal receptive fields at different mean
      light levels, we find that changes in input from ON and OFF pathways in receptive
      field centers underlie shifts in contrast preference. Sw2-RGCs exhibit direction
      selective responses to motion stimuli. Despite changing contrast preference,
      direction selectivity of Sw2-RGCs and other RGCs as well as orientation-selective
      responses of RGCs remain stable across light levels.

PMID- 25995352
TI  - Cell type- and activity-dependent extracellular correlates of intracellular
      spiking.
AB  - Despite decades of extracellular action potential (EAP) recordings monitoring
      brain activity, the biophysical origin and inherent variability of these signals
      remain enigmatic. We performed whole cell patch recordings of excitatory and
      inhibitory neurons in rat somatosensory cortex slice while positioning a silicon
      probe in their vicinity to concurrently record intra- and extracellular voltages
      for spike frequencies under 20 Hz. We characterize biophysical events and
      properties (intracellular spiking, extracellular resistivity, temporal jitter,
      etc.) related to EAP recordings at the single-neuron level in a layer-specific
      manner. Notably, EAP amplitude was found to decay as the inverse of distance
      between the soma and the recording electrode with similar (but not identical)
      resistivity across layers. Furthermore, we assessed a number of EAP features and
      their variability with spike activity: amplitude (but not temporal) features
      varied substantially (~ 30-50% compared with mean) and nonmonotonically as a
      function of spike frequency and spike order. Such EAP variation only partly
      reflects intracellular somatic spike variability and points to the plethora of
      processes contributing to the EAP. Also, we show that the shape of the EAP
      waveform is qualitatively similar to the negative of the temporal derivative to
      the intracellular somatic voltage, as expected from theory. Finally, we tested to
      what extent EAPs can impact the lowpass-filtered part of extracellular
      recordings, the local field potential (LFP), typically associated with synaptic
      activity. We found that spiking of excitatory neurons can significantly impact
      the LFP at frequencies as low as 20 Hz. Our results question the common assertion
      that the LFP acts as proxy for synaptic activity.

PMID- 25995353
TI  - Context cue-dependent saccadic adaptation in rhesus macaques cannot be elicited
      using color.
AB  - When the head does not move, rapid movements of the eyes called saccades are used
      to redirect the line of sight. Saccades are defined by a series of metrical and
      kinematic (evolution of a movement as a function of time) relationships. For
      example, the amplitude of a saccade made from one visual target to another is
      roughly 90% of the distance between the initial fixation point (T0) and the
      peripheral target (T1). However, this stereotypical relationship between saccade
      amplitude and initial retinal error (T1-T0) may be altered, either increased or
      decreased, by surreptitiously displacing a visual target during an ongoing
      saccade. This form of motor learning (called saccadic adaptation) has been
      described in both humans and monkeys. Recent experiments in humans and monkeys
      have suggested that internal (proprioceptive) and external (target shape, color,
      and/or motion) cues may be used to produce context-dependent adaptation. We
      tested the hypothesis that an external contextual cue (target color) could be
      used to evoke differential gain (actual saccade/initial retinal error) states in
      rhesus monkeys. We did not observe differential gain states correlated with
      target color regardless of whether targets were displaced along the same vector
      as the primary saccade or perpendicular to it. Furthermore, this observation held
      true regardless of whether adaptation trials using various colors and
      intrasaccade target displacements were randomly intermixed or presented in short
      or long blocks of trials. These results are consistent with hypotheses that state
      that color cannot be used as a contextual cue and are interpreted in light of
      previous studies of saccadic adaptation in both humans and monkeys. 

PMID- 25995354
TI  - Speed-accuracy tradeoff by a control signal with balanced excitation and
      inhibition.
AB  - A hallmark of flexible behavior is the brain's ability to dynamically adjust
      speed and accuracy in decision-making. Recent studies suggested that such
      adjustments modulate not only the decision threshold, but also the rate of
      evidence accumulation. However, the underlying neuronal-level mechanism of the
      rate change remains unclear. In this work, using a spiking neural network model
      of perceptual decision, we demonstrate that speed and accuracy of a decision
      process can be effectively adjusted by manipulating a top-down control signal
      with balanced excitation and inhibition [balanced synaptic input (BSI)]. Our
      model predicts that emphasizing accuracy over speed leads to reduced rate of
      ramping activity and reduced baseline activity of decision neurons, which have
      been observed recently at the level of single neurons recorded from behaving
      monkeys in speed-accuracy tradeoff tasks. Moreover, we found that an increased
      inhibitory component of BSI skews the decision time distribution and produces a
      pronounced exponential tail, which is commonly observed in human studies. Our
      findings suggest that BSI can serve as a top-down control mechanism to rapidly
      and parametrically trade between speed and accuracy, and such a cognitive control
      signal presents both when the subjects emphasize accuracy or speed in perceptual
      decisions. 

PMID- 25995355
TI  - Reduced postactivation depression of soleus H reflex and root evoked potential
      after transcranial magnetic stimulation.
AB  - Postactivation depression of the Hoffmann (H) reflex is associated with a
      transient period of suppression following activation of the reflex pathway. In
      soleus, the depression lasts for 100-200 ms during voluntary contraction and up
      to 10 s at rest. A reflex root evoked potential (REP), elicited after a single
      pulse of transcutaneous stimulation to the thoracolumbar spine, has been shown to
      exhibit similar suppression. The present study systematically characterized the
      effect of transcranial magnetic stimulation (TMS) on postactivation depression
      using double-pulse H reflexes and REPs. A TMS pulse reduced the period of
      depression to 10-15 ms for both reflexes. TMS could even produce postactivation
      facilitation of the H reflex, as the second reflex response was increased to 243
      +/- 51% of control values at the 75-ms interval. The time course was
      qualitatively similar for the REP, yet the overall increase was less. While
      recovery of the H reflex was slower in the relaxed muscle, the profile exhibited
      a distinct bimodal shape characterized by an early peak at the 25-ms interval,
      reaching 72 +/- 23% of control values, followed by a trough at 50 ms, and then a
      gradual recovery at intervals > 50 ms. The rapid recovery of two successively
      depressed H reflexes, ~ 25 ms apart, was also possible with double-pulse TMS. The
      effect of the TMS-induced corticospinal excitation on postactivation depression
      may be explained by a combination of pre- and postsynaptic mechanisms, although
      further investigation is required to distinguish between them.

PMID- 25995356
TI  - A conserved role for Notch signaling in priming the cellular response to Shh
      through ciliary localisation of the key Shh transducer Smo.
AB  - Notochord-derived Sonic Hedgehog (Shh) is essential for dorsoventral patterning
      of the overlying neural tube. Increasing concentration and duration of Shh signal
      induces progenitors to acquire progressively more ventral fates. We show that
      Notch signalling augments the response of neuroepithelial cells to Shh, leading
      to the induction of higher expression levels of the Shh target gene Ptch1 and
      subsequently induction of more ventral cell fates. Furthermore, we demonstrate
      that activated Notch1 leads to pronounced accumulation of Smoothened (Smo) within
      primary cilia and elevated levels of full-length Gli3. Finally, we show that
      Notch activity promotes longer primary cilia both in vitro and in vivo.
      Strikingly, these Notch-regulated effects are Shh independent. These data
      identify Notch signalling as a novel modulator of Shh signalling that acts
      mechanistically via regulation of ciliary localisation of key components of its
      transduction machinery. 

PMID- 25995357
TI  - The role of intervening hospital admissions on trajectories of disability in the
      last year of life: prospective cohort study of older people.
AB  - OBJECTIVE: To evaluate the role of intervening hospital admissions on
      trajectories of disability in the last year of life. DESIGN: Prospective cohort
      study. SETTING: Greater New Haven, Connecticut, United States, from March 1998 to
      June 2013. PARTICIPANTS: 552 decedents from a cohort of 754 community living
      people, aged 70 years or older, who were initially non-disabled in four essential
      activities of daily living: bathing, dressing, walking, and transferring. MAIN
      OUTCOME MEASURE: Occurrence of admissions to hospital and severity of disability
      (range 0-4), ascertained during monthly interviews for more than 15 years.
      RESULTS: In the last year of life, six distinct trajectories of disability were
      identified, from least disabled to most disabled: 95 participants (17.2%) had no
      disability, 61 (11.1%) had catastrophic disability, 53 (9.6%) had accelerated
      disability, 61 (11.1%) had progressively mild disability, 127 (23.0%) had
      progressively severe disability, and 155 (28.1%) had persistently severe
      disability. 392 (71.0%) participants had at least one hospital admission and 248
      (44.9%) had multiple hospital admissions. For each trajectory the course of
      disability closely tracked the monthly prevalence of hospital admission. In a set
      of multivariable models that included several potential confounders, hospital
      admission in a given month had a strong independent effect on the severity of
      disability, in both relative and absolute terms. The largest absolute effect was
      observed for catastrophic disability, with a mean increase in disability score of
      1.9 (95% confidence interval 1.5 to 2.4) in the setting of a hospital admission,
      corresponding to a rate ratio (or relative effect) of 2.0 (95% confidence
      interval 1.5 to 2.7). CONCLUSIONS: In the last year of life, acute hospital
      admissions play an important role in the disabling process. Knowledge about the
      course of disability before these intervening events may facilitate clinical
      decision making at the end of life. For older patients admitted to hospital with
      progressive or persistent levels of severe disability, representing more than
      half of the decedents, clinicians might consider a palliative care approach to
      facilitate discussions about advance care planning and to better deal with
      personal care needs.

PMID- 25995358
TI  - Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in
      the Development of Diabetic Nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease. It is
      pathologically characterized by the accumulation of extracellular matrix in the
      mesangium, of which the main component is alpha1/alpha2 type IV collagen
      (Col4a1/a2). Recently, we identified Smad1 as a direct regulator of Col4a1/a2
      under diabetic conditions in vitro. Here, we demonstrate that Smad1 plays a key
      role in diabetic nephropathy through bone morphogenetic protein 4 (BMP4) in vivo.
      Smad1-overexpressing mice (Smad1-Tg) were established, and diabetes was induced
      by streptozotocin. Nondiabetic Smad1-Tg did not exhibit histological changes in
      the kidney; however, the induction of diabetes resulted in an ~1.5-fold greater
      mesangial expansion, consistent with an increase in glomerular phosphorylated
      Smad1. To address regulatory factors of Smad1, we determined that BMP4 and its
      receptor are increased in diabetic glomeruli and that diabetic Smad1-Tg and wild
      type mice treated with a BMP4-neutralizing antibody exhibit decreased Smad1
      phosphorylation and ~40% less mesangial expansion than those treated with control
      IgG. Furthermore, heterozygous Smad1 knockout mice exhibit attenuated mesangial
      expansion in the diabetic condition. The data indicate that BMP4/Smad1 signaling
      is a critical cascade for the progression of mesangial expansion and that
      blocking this signal could be a novel therapeutic strategy for diabetic
      nephropathy. 

PMID- 25995360
TI  - Care at end of life isn't being properly managed, says ombudsman.

PMID- 25995359
TI  - Treatment effects of fixed functional appliances in patients with Class II
      malocclusion: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the treatment effects of fixed functional appliances (FFAs)
      in treated versus untreated Class II patients by means of lateral cephalometric
      radiographs. SEARCH METHODS: Unrestricted electronic search of 18 databases and
      additional manual searches up to October 2014. SELECTION CRITERIA: Prospective
      randomized and non-randomized controlled trials reporting on cephalometric
      angular measurements of Class II patients treated with FFAs and their matched
      untreated controls. DATA COLLECTION AND ANALYSIS: Skeletal, dental, and soft
      tissue cephalometric data were annualized and stratified according to the time of
      evaluation in effects. Following risk of bias evaluation, the mean differences
      (MDs) and 95 % confidence intervals (CIs) were calculated with random-effects
      models. Patient- and appliance-related subgroup analyses and sensitivity analyses
      were performed with mixed-effects models. RESULTS: Nine studies were included
      (244 patients; mean age: 13.5 years and 174 untreated controls; mean age: 12.8
      years) reporting on cephalometric effects directly after the removal of FFAs.
      FFAs were found to induce a small reduction of SNA angle (MD = -0.83 degree/year,
      95 % CI: -1.17 to -0.48), a small increase of SNB angle (MD = 0.87 degree/year,
      95 % CI: 0.30-1.43), and moderate decrease of ANB angle (MD = -1.74 degree/year,
      95 % CI: -2.50 to -0.98) compared to untreated Class II patients. FFA treatment
      resulted in significant dentoalveolar and soft tissue changes. Several patient-
      or appliance-related factors seem to affect the treatment outcome. Long-term
      effectiveness of FFAs could not be assessed due to limited evidence. CONCLUSIONS:
      According to existing evidence, FFAs seem to be effective in improving Class II
      malocclusion in the short term, although their effects seem to be mainly
      dentoalveolar rather than skeletal.

PMID- 25995361
TI  - Medicine and abortion law: complicating the reforming profession.
AB  - The complicated intra-professional rivalries that have contributed to the current
      contours of abortion law and service provision have been subject to limited
      academic engagement. In this article, we address this gap. We examine how the
      competing interests of different specialisms played out in abortion law reform
      from the early twentieth-century, through to the enactment of the Abortion Act
      1967, and the formation of the structures of abortion provision in the early
      1970s. We demonstrate how professional interests significantly shaped the
      landscape of abortion law in England, Scotland, and Wales. Our analysis addresses
      two distinct and yet related fields where professional interests were negotiated
      or asserted in the journey to law reform. Both debates align with earlier
      analysis that has linked abortion law reform with the market development of the
      medical profession. We argue that these two axes of debate, both dominated by
      professional interests, interacted to help shape law's treatment of abortion, and
      continue to influence the provision of abortion services today. 

PMID- 25995363
TI  - Measuring the signal-to-noise ratio of a neuron.
AB  - The signal-to-noise ratio (SNR), a commonly used measure of fidelity in physical
      systems, is defined as the ratio of the squared amplitude or variance of a signal
      relative to the variance of the noise. This definition is not appropriate for
      neural systems in which spiking activity is more accurately represented as point
      processes. We show that the SNR estimates a ratio of expected prediction errors
      and extend the standard definition to one appropriate for single neurons by
      representing neural spiking activity using point process generalized linear
      models (PP-GLM). We estimate the prediction errors using the residual deviances
      from the PP-GLM fits. Because the deviance is an approximate chi(2) random
      variable, we compute a bias-corrected SNR estimate appropriate for single-neuron
      analysis and use the bootstrap to assess its uncertainty. In the analyses of four
      systems neuroscience experiments, we show that the SNRs are -10 dB to -3 dB for
      guinea pig auditory cortex neurons, -18 dB to -7 dB for rat thalamic neurons, -28
      dB to -14 dB for monkey hippocampal neurons, and -29 dB to -20 dB for human
      subthalamic neurons. The new SNR definition makes explicit in the measure
      commonly used for physical systems the often-quoted observation that single
      neurons have low SNRs. The neuron's spiking history is frequently a more
      informative covariate for predicting spiking propensity than the applied
      stimulus. Our new SNR definition extends to any GLM system in which the factors
      modulating the response can be expressed as separate components of a likelihood
      function. 

PMID- 25995364
TI  - Basolateral amygdala bidirectionally modulates stress-induced hippocampal
      learning and memory deficits through a p25/Cdk5-dependent pathway.
AB  - Repeated stress has been suggested to underlie learning and memory deficits via
      the basolateral amygdala (BLA) and the hippocampus; however, the functional
      contribution of BLA inputs to the hippocampus and their molecular repercussions
      are not well understood. Here we show that repeated stress is accompanied by
      generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation
      and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and
      reduced expression of memory-related genes in the hippocampus. A combination of
      optogenetic and pharmacosynthetic approaches shows that BLA activation is both
      necessary and sufficient for stress-associated molecular changes and memory
      impairments. Furthermore, we show that this effect relies on direct glutamatergic
      projections from the BLA to the dorsal hippocampus. Finally, we show that p25
      generation is necessary for the stress-induced memory dysfunction. Taken
      together, our data provide a neural circuit model for stress-induced hippocampal
      memory deficits through BLA activity-dependent p25 generation. 

PMID- 25995367
TI  - UK children are more than twice as likely to be obese than previous generations,
      figures show.

PMID- 25995365
TI  - Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1.
AB  - The response to an innate immune challenge is conditioned by the time of day, but
      the molecular basis for this remains unclear. In myeloid cells, there is a
      temporal regulation to induction by lipopolysaccharide (LPS) of the
      proinflammatory microRNA miR-155 that correlates inversely with levels of BMAL1.
      BMAL1 in the myeloid lineage inhibits activation of NF-kappaB and miR-155
      induction and protects mice from LPS-induced sepsis. Bmal1 has two miR-155
      binding sites in its 3'-UTR, and, in response to LPS, miR-155 binds to these two
      target sites, leading to suppression of Bmal1 mRNA and protein in mice and
      humans. miR-155 deletion perturbs circadian function, gives rise to a shorter
      circadian day, and ablates the circadian effect on cytokine responses to LPS.
      Thus, the molecular clock controls miR-155 induction that can repress BMAL1
      directly. This leads to an innate immune response that is variably responsive to
      challenges across the circadian day. 

PMID- 25995366
TI  - Integration of plastids with their hosts: Lessons learned from dinoflagellates.
AB  - After their endosymbiotic acquisition, plastids become intimately connected with
      the biology of their host. For example, genes essential for plastid function may
      be relocated from the genomes of plastids to the host nucleus, and pathways may
      evolve within the host to support the plastid. In this review, we consider the
      different degrees of integration observed in dinoflagellates and their associated
      plastids, which have been acquired through multiple different endosymbiotic
      events. Most dinoflagellate species possess plastids that contain the pigment
      peridinin and show extreme reduction and integration with the host biology. In
      some species, these plastids have been replaced through serial endosymbiosis with
      plastids derived from a different phylogenetic derivation, of which some have
      become intimately connected with the biology of the host whereas others have not.
      We discuss in particular the evolution of the fucoxanthin-containing
      dinoflagellates, which have adapted pathways retained from the ancestral
      peridinin plastid symbiosis for transcript processing in their current, serially
      acquired plastids. Finally, we consider why such a diversity of different degrees
      of integration between host and plastid is observed in different dinoflagellates
      and how dinoflagellates may thus inform our broader understanding of plastid
      evolution and function. 

PMID- 25995369
TI  - Brain drain: final year medical students' intentions of training abroad.
AB  - BACKGROUND: In Croatia, a new European Union (EU) member state since July 2013,
      there is already a shortage of around 3280 doctors to reach the European average.
      OBJECTIVES: To investigate the emigration intentions of the current cohort of
      final year medical students at Zabreb School of Medicine. METHODS: An electronic
      questionnaire was used in June 2013 to assess the attitudes of 232 final year
      medical students towards working conditions abroad and expectations for career
      opportunities in Croatia following accession to the EU. RESULTS: With an overall
      response rate of 87%, more than half of the surveyed students (106/202, 53%)
      intended to travel abroad, either for specialty (52/202, 26%) or subspecialty
      (54/202, 27%) training. More female students (58/135, 43%) than male students
      (17/62, 27%) indicated they would not emigrate. Most attractive emigration
      destinations were: Germany (34/121, 28%), USA (19/121, 16%), the UK (19/121,
      16%), Switzerland (16/121, 13%) and Canada (11/121, 9%). The most important goals
      that respondents aimed to achieve through training abroad were to excel
      professionally (45/120, 38%), to prosper financially (20/120, 17%) and to acquire
      new experiences and international exposure (31/120, 26%). CONCLUSIONS: Students'
      motivating factors, goals for and positive beliefs about training abroad, as well
      as negative expectations regarding career opportunities in Croatia, may point
      towards actions that could be taken to help make Croatia a country that
      facilitates medical education and professional career development of young
      doctors.

PMID- 25995370
TI  - Among politicians, patients and nurse leaders: what can a nurse ethicist
      contribute?

PMID- 25995373
TI  - The Growing Public Health Challenges of Exposure to Ultraviolet Radiation From
      Use of Indoor Tanning Devices in the United States.
AB  - Ultraviolet radiation is recognized as a human carcinogen by the International
      Agency for Research on Cancer, the world's authority on cancer research. In
      particular, exposure to ultraviolet radiation can lead to melanoma of the skin,
      which is the deadliest form of skin cancer in the United States. Yet despite the
      significant public health burden that is associated with skin cancer in the
      United States, each year over a million Americans engage in indoor tanning where
      exposure to artificial ultraviolet radiation occurs. In this article, we argue
      for an immediate ban on the use of commercial indoor tanning by minors and, based
      on international precedents, the phasing out of all commercial tanning operations
      in the United States. We consider the use of indoor tanning devices in the United
      States, epidemiological data on indoor tanning devices and cancer, regulation of
      tanning devices, and scientific evidence for increased government intervention. 

PMID- 25995374
TI  - Informal Workers in Thailand: Occupational Health and Social Security
      Disparities.
AB  - Informal workers in Thailand lack employee status as defined under the Labor
      Protection Act (LPA). Typically, they do not work at an employer's premise; they
      work at home and may be self-employed or temporary workers. They account for 62.6
      percent of the Thai workforce and have a workplace accident rate ten times higher
      than formal workers. Most Thai Labor laws apply only to formal workers, but some
      protect informal workers in the domestic, home work, and agricultural sectors.
      Laws that protect informal workers lack practical enforcement mechanisms and are
      generally ineffective because informal workers lack employment contracts and
      awareness of their legal rights. Thai social security laws fail to provide
      informal workers with treatment of work-related accidents, diseases, and
      injuries; unemployment and retirement insurance; and workers' compensation. The
      article summarizes the differences in protections available for formal and
      informal sector workers and measures needed to decrease these disparities in
      coverage. 

PMID- 25995375
TI  - P-body assembly requires DDX6 repression complexes rather than decay or
      Ataxin2/2L complexes.
AB  - P-bodies are cytoplasmic ribonucleoprotein granules involved in
      posttranscriptional regulation. DDX6 is a key component of their assembly in
      human cells. This DEAD-box RNA helicase is known to be associated with various
      complexes, including the decapping complex, the CPEB repression complex, RISC,
      and the CCR4/NOT complex. To understand which DDX6 complexes are required for P
      body assembly, we analyzed the DDX6 interactome using the tandem-affinity
      purification methodology coupled to mass spectrometry. Three complexes were
      prominent: the decapping complex, a CPEB-like complex, and an Ataxin2/Ataxin2L
      complex. The exon junction complex was also found, suggesting DDX6 binding to
      newly exported mRNAs. Finally, some DDX6 was associated with polysomes, as
      previously reported in yeast. Despite its high enrichment in P-bodies, most DDX6
      is localized out of P-bodies. Of the three complexes, only the decapping and CPEB
      like complexes were recruited into P-bodies. Investigation of P-body assembly in
      various conditions allowed us to distinguish required proteins from those that
      are dispensable or participate only in specific conditions. Three proteins were
      required in all tested conditions: DDX6, 4E-T, and LSM14A. These results reveal
      the variety of pathways of P-body assembly, which all nevertheless share three
      key factors connecting P-body assembly to repression. 

PMID- 25995376
TI  - Endosomal regulation of contact inhibition through the AMOT:YAP pathway.
AB  - Contact-mediated inhibition of cell proliferation is an essential part of organ
      growth control; the transcription coactivator Yes-associated protein (YAP) plays
      a pivotal role in this process. In addition to phosphorylation-dependent
      regulation of YAP, the integral membrane protein angiomotin (AMOT) and AMOT
      family members control YAP through direct binding. Here we report that regulation
      of YAP activity occurs at the endosomal membrane through a dynamic interaction of
      AMOT with an endosomal integral membrane protein, endotubin (EDTB). EDTB
      interacts with both AMOT and occludin and preferentially associates with occludin
      in confluent cells but with AMOT family members in subconfluent cells. EDTB
      competes with YAP for binding to AMOT proteins in subconfluent cells.
      Overexpression of the cytoplasmic domain or full-length EDTB induces
      translocation of YAP to the nucleus, an overgrowth phenotype, and growth in soft
      agar. This increase in proliferation is dependent upon YAP activity and is
      complemented by overexpression of p130-AMOT. Furthermore, overexpression of EDTB
      inhibits the AMOT:YAP interaction. EDTB and AMOT have a greater association in
      subconfluent cells compared with confluent cells, and this association is
      regulated at the endosomal membrane. These data provide a link between the
      trafficking of tight junction proteins through endosomes and contact-inhibition
      regulated cell growth. 

PMID- 25995377
TI  - Cdc6 degradation requires phosphodegron created by GSK-3 and Cdk1 for SCFCdc4
      recognition in Saccharomyces cerevisiae.
AB  - To ensure genome integrity, DNA replication takes place only once per cell cycle
      and is tightly controlled by cyclin-dependent kinase (Cdk1). Cdc6p is part of the
      prereplicative complex, which is essential for DNA replication. Cdc6 is
      phosphorylated by cyclin-Cdk1 to promote its degradation after origin firing to
      prevent DNA rereplication. We previously showed that a yeast GSK-3 homologue,
      Mck1 kinase, promotes Cdc6 degradation in a SCF(Cdc4)-dependent manner, therefore
      preventing rereplication. Here we present evidence that Mck1 directly
      phosphorylates a GSK-3 consensus site in the C-terminus of Cdc6. The Mck1
      dependent Cdc6 phosphorylation required priming by cyclin/Cdk1 at an adjacent CDK
      consensus site. The sequential phosphorylation by Mck1 and Clb2/Cdk1 generated a
      Cdc4 E3 ubiquitin ligase-binding motif to promote Cdc6 degradation during
      mitosis. We further revealed that Cdc6 degradation triggered by Mck1 kinase was
      enhanced upon DNA damage caused by the alkylating agent methyl methanesulfonate
      and that the resulting degradation was mediated through Cdc4. Thus, Mck1 kinase
      ensures proper DNA replication, prevents DNA damage, and maintains genome
      integrity by inhibiting Cdc6. 

PMID- 25995378
TI  - Protein degradation corrects for imbalanced subunit stoichiometry in OST complex
      assembly.
AB  - Protein degradation is essential for cellular homeostasis. We developed a
      sensitive approach to examining protein degradation rates in Saccharomyces
      cerevisiae by coupling a SILAC approach to selected reaction monitoring (SRM)
      mass spectrometry. Combined with genetic tools, this analysis made it possible to
      study the assembly of the oligosaccharyl transferase complex. The ER-associated
      degradation machinery compensated for disturbed homeostasis of complex components
      by degradation of subunits in excess. On a larger scale, protein degradation in
      the ER was found to be a minor factor in the regulation of protein homeostasis in
      exponentially growing cells, but ERAD became relevant when the gene dosage was
      affected, as demonstrated in heterozygous diploid cells. Hence the alleviation of
      fitness defects due to abnormal gene copy numbers might be an important function
      of protein degradation. 

PMID- 25995379
TI  - The HOPS/class C Vps complex tethers membranes by binding to one Rab GTPase in
      each apposed membrane.
AB  - Many Rab GTPase effectors are membrane-tethering factors, that is, they
      physically link two apposed membranes before intracellular membrane fusion. In
      this study, we investigate the distinct binding factors needed on apposed
      membranes for Rab effector-dependent tethering. We show that the homotypic fusion
      and protein-sorting/class C vacuole protein-sorting (HOPS/class C Vps) complex
      can tether low-curvature membranes, that is, liposomes with a diameter of ~100
      nm, only when the yeast vacuolar Rab GTPase Ypt7p is present in both tethered
      membranes. When HOPS is phosphorylated by the vacuolar casein kinase I, Yck3p,
      tethering only takes place when GTP-bound Ypt7p is present in both tethered
      membranes. When HOPS is not phosphorylated, however, its tethering activity shows
      little specificity for the nucleotide-binding state of Ypt7p. These results
      suggest a model for HOPS-mediated tethering in which HOPS tethers membranes by
      binding to Ypt7p in each of the two tethered membranes. Moreover, because vacuole
      associated HOPS is presumably phosphorylated by Yck3p, our results suggest that
      nucleotide exchange of Ypt7p on multivesicular bodies (MVBs)/late endosomes must
      take place before HOPS can mediate tethering at vacuoles. 

PMID- 25995380
TI  - An ELMO2-RhoG-ILK network modulates microtubule dynamics.
AB  - ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell
      motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG,
      forming tripartite ERI complexes. These complexes are involved in promoting beta1
      integrin-dependent directional migration in undifferentiated epidermal
      keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule
      regulation at integrin-containing focal adhesions. During differentiation,
      epidermal keratinocytes cease to express integrins, but ERI complexes persist.
      Here we show an integrin-independent role of ERI complexes in modulation of
      microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes
      by inactivating the Ilk gene in these cells reduces microtubule growth and
      increases the frequency of catastrophe. Reciprocally, exogenous expression of
      ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present.
      Mechanistically, activation of Rac1 downstream from ERI complexes mediates their
      effects on microtubule stability. In this pathway, Rac1 serves as a hub to
      modulate microtubule dynamics through two different routes: 1) phosphorylation
      and inactivation of the microtubule-destabilizing protein stathmin and 2)
      phosphorylation and inactivation of GSK-3beta, which leads to the activation of
      CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI
      species impairs Ca(2+)-mediated formation of adherens junctions, critical to
      maintaining mechanical integrity in the epidermis. Our findings support a key
      role for ERI species in integrin-independent stabilization of the microtubule
      network in differentiated keratinocytes. 

PMID- 25995381
TI  - Identification of lamin B-regulated chromatin regions based on chromatin
      landscapes.
AB  - Lamins, the major structural components of the nuclear lamina (NL) found beneath
      the nuclear envelope, are known to interact with most of the nuclear peripheral
      chromatin in metazoan cells. Although NL-chromatin associations correlate with a
      repressive chromatin state, the role of lamins in tethering chromatin to NL and
      how such tether influences gene expression have remained challenging to decipher.
      Studies suggest that NL proteins regulate chromatin in a context-dependent
      manner. Therefore understanding the context of chromatin states based on genomic
      features, including chromatin-NL interactions, is important to the study of
      lamins and other NL proteins. By modeling genome organization based on
      combinatorial patterns of chromatin association with lamin B1, core histone
      modification, and core and linker histone occupancy, we report six distinct large
      chromatin landscapes, referred to as histone lamin landscapes (HiLands)-red (R), 
      orange (O), -yellow (Y), -green (G), -blue (B), and -purple (P), in mouse
      embryonic stem cells (mESCs). This HiLands model demarcates the previously mapped
      lamin-associated chromatin domains (LADs) into two HiLands, HiLands-B and HiLands
      P, which are similar to facultative and constitutive heterochromatins,
      respectively. Deletion of B-type lamins in mESCs caused a reduced interaction
      between regions of HiLands-B and NL as measured by emerin-chromatin interaction.
      Our findings reveal the importance of analyzing specific chromatin types when
      studying the function of NL proteins in chromatin tether and regulation. 

PMID- 25995383
TI  - Lesion Characteristics of Individuals With Upper Limb Spasticity After Stroke.
AB  - This study explores the relationship between lesion location and volume and upper
      limb spasticity after stroke. Ninety-seven stroke patients (51 with spasticity)
      were included in the analysis (age = 67.5 +/- 13.3 years, 57 males). Lesions were
      traced from computed tomography and magnetic resonance images and coregistered to
      a symmetrical brain template. Lesion overlays from the nonspastic group were
      subtracted from the spastic group to determine the regions of the brain more
      commonly lesioned in spastic patients. Similar analysis was performed across
      groups of participants whose upper limb (elbow or wrist) Modified Ashworth Scale
      (MAS) score ranged from 1 (mild) to 4 (severe). Following subtraction analysis
      and Fisher's exact test, the putamen was identified as the area most frequently
      lesioned in individuals with spasticity. More severe spasticity was associated
      with a higher lesion volume. This study establishes the neuroanatomical
      correlates of poststroke spasticity and describes the relationship between lesion
      characteristics and the severity of spasticity using mixed brain imaging
      modalities, including computed tomography imaging, which is more readily
      available to clinicians. Understanding the association between lesion location
      and volume with the development and severity of spasticity is an important first
      step toward predicting the development of spasticity after stroke. Such
      information could inform the implementation of intervention strategies during the
      recovery process to minimize the extent of impairment. 

PMID- 25995382
TI  - Intermolecular interactions of thrombospondins drive their accumulation in
      extracellular matrix.
AB  - Thrombospondins participate in many aspects of tissue organization in adult
      tissue homeostasis, and their dysregulation contributes to pathological processes
      such as fibrosis and tumor progression. The incorporation of thrombospondins into
      extracellular matrix (ECM) as discrete puncta has been documented in various
      tissue and cell biological contexts, yet the underlying mechanisms remain poorly
      understood. We find that collagen fibrils are disorganized in multiple tissues of
      Thbs1(-/-) mice. In investigating how thrombospondins become retained within ECM
      and thereby affect ECM organization, we find that accumulation of thrombospondin
      1 or thrombospondin-5 puncta within cell-derived ECM is controlled by a novel,
      conserved, surface-exposed site on the thrombospondin L-type lectin domain. This
      site acts to recruit thrombospondin molecules into ECM by intermolecular
      interactions in trans. This mechanism is fibronectin independent, can take place
      extracellularly, and is demonstrated to be direct in vitro. The trans
      intermolecular interactions can also be heterotypic-for example, between
      thrombospondin-1 and thrombospondin-5. These data identify a novel concept of
      concentration-dependent, intermolecular "matrix trapping" as a conserved
      mechanism that controls the accumulation and thereby the functionality of
      thrombospondins in ECM. 

PMID- 25995384
TI  - ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM.
AB  - The excessive metastatic propensity of melanoma makes it the most deadly form of
      skin cancer, yet the underlying mechanism of metastasis remains elusive. Here,
      mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3
      and associated downregulation of the zinc finger transcription factor ZBTB7A in
      metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified
      MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an
      integrated approach, it is demonstrated that ZBTB7A directly binds to the
      promoter and transcriptionally represses the expression of MCAM, establishing
      ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently,
      downregulation of ZBTB7A results in marked upregulation of MCAM and enhanced
      melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM
      expression in association with melanoma metastasis is further validated with data
      from analysis of human melanoma specimens. IMPLICATIONS: Together, these results
      uncover a previously unrecognized role of ZBTB7A in negative regulation of
      melanoma metastasis and have important clinical implications.

PMID- 25995386
TI  - Permanent trans-venous pacing in an extra-cardiac Fontan circulation.
AB  - AIMS: In patients with an extra-cardiac Fontan circulation, there is no direct
      access to the heart. The insertion of a permanent pacemaker requires surgery to
      insert epicardial pacing wires. We present the implantation of a permanent
      endocardial pacing lead from the superior vena cava (SVC) into the atrium via
      direct passage from the right pulmonary artery (RPA). METHODS AND RESULTS: A
      permanent pacing lead was passed directly from the SVC to the RPA and then into
      the atrial mass. Direct passage from the RPA (attached directly to the right SVC)
      into the atrial mass was achieved using a trans-septal puncture needle.
      CONCLUSION: This novel technique is an alternative to epicardial pacing in
      patients with an extra-cardiac Fontan circulation, thus avoiding the need for
      surgical intervention. It may also be applied to gain access to the atrial mass
      for arrhythmia ablation therapy.

PMID- 25995385
TI  - Transposon Mutagenesis Screen Identifies Potential Lung Cancer Drivers and CUL3
      as a Tumor Suppressor.
AB  - Non-small cell lung cancers (NSCLC) harbor thousands of passenger events that
      hide genetic drivers. Even highly recurrent events in NSCLC, such as mutations in
      PTEN, EGFR, KRAS, and ALK, are detected, at most, in only 30% of patients. Thus,
      many unidentified low-penetrant events are causing a significant portion of lung
      cancers. To detect low-penetrance drivers of NSCLC, a forward genetic screen was
      performed in mice using the Sleeping Beauty (SB) DNA transposon as a random
      mutagen to generate lung tumors in a Pten-deficient background. SB mutations
      coupled with Pten deficiency were sufficient to produce lung tumors in 29% of
      mice. Pten deficiency alone, without SB mutations, resulted in lung tumors in 11%
      of mice, whereas the rate in control mice was approximately 3%. In addition,
      thyroid cancer and other carcinomas, as well as the presence of bronchiolar and
      alveolar epithelialization, in mice deficient for Pten were also identified.
      Analysis of common transposon insertion sites identified 76 candidate cancer
      driver genes. These genes are frequently dysregulated in human lung cancers and
      implicate several signaling pathways. Cullin3 (Cul3), a member of a ubiquitin
      ligase complex that plays a role in the oxidative stress response pathway, was
      identified in the screen and evidence demonstrates that Cul3 functions as a tumor
      suppressor. IMPLICATIONS: This study identifies many novel candidate genetic
      drivers of lung cancer and demonstrates that CUL3 acts as a tumor suppressor by
      regulating oxidative stress.

PMID- 25995387
TI  - The ventricular tachycardia score: a novel approach to electrocardiographic
      diagnosis of ventricular tachycardia.
AB  - AIMS: Electrocardiographic diagnosis of wide QRS complex tachycardia (WCT)
      continues to be challenging as none one of the available methods is specific for
      ventricular tachycardia (VT) diagnosis. We aimed to construct a method for WCT
      differentiation based on a scoring system, in which ECGs are graded according to
      the number of VT-specific features. This novel method was validated and compared
      with Brugada algorithm and other methods. METHODS AND RESULTS: A total of 786
      WCTs (512 VTs) from 587 consecutive patients with a proven diagnosis were
      analysed by two blinded observers. The VT score method was based on seven ECG
      features: initial R wave in V1, initial r > 40 ms in V1/V2, notched S in V1,
      initial R in aVR, lead II R wave peak time >=50 ms, no RS in V1-V6, and
      atrioventricular dissociation. Atrioventricular dissociation was assigned two
      points, and each of the other features was assigned one point. The overall
      accuracy of VT score >=1 for VT diagnosis (83%) was higher than that of the aVR
      (72%, P = 0.001) and Brugada (81%) algorithms. Ventricular tachycardia score >=3
      was present in 66% of VTs and was more specific (99.6%) than any other
      algorithm/criterion for VT diagnosis. Ventricular tachycardia score >=4 was
      present in 33% of VTs and was 100% specific for VT. CONCLUSION: The new ECG-based
      method provides a certain diagnosis of VT in the majority of patients with VT,
      identifies unequivocal ECGs, and has superior overall diagnostic accuracy to
      other ECG methods.

PMID- 25995388
TI  - The role of preprocedural monocyte-to-high-density lipoprotein ratio in
      prediction of atrial fibrillation recurrence after cryoballoon-based catheter
      ablation.
AB  - AIMS: Previous studies evidenced that increased monocyte count or activity and
      lower high-density lipoprotein (HDL) cholesterol levels were associated with more
      prevalent atrial fibrillation (AF) which attributed to pro-inflammatory and pro
      oxidant effects. Monocyte-to-HDL ratio (M/H ratio) is a recently emerged
      indicator of inflammation and oxidative stress which have been only studied in
      patients with chronic kidney disease. We aimed to investigate the prognostic
      impact of M/H ratio on AF recurrence after cryoballoon-based catheter ablation.
      METHODS AND RESULTS: A total of 402 patients (43.5% female, age 53.5 +/- 10.9
      years, and 80.8% paroxysmal AF) with symptomatic AF underwent initial
      cryoablation procedure. Patients were categorized into quartiles on the basis of
      their pre-procedural M/H ratio. Post-ablation blanking period was observed for 3
      months. At a mean follow-up of 20.6 +/- 6.0 months, 95 patients (23.6%) had
      developed AF recurrence. Atrial fibrillation recurrence rates from the lowest to
      the highest M/H ratio quartiles were 7.4, 7.4, 16.8, and 68.4%, respectively (P <
      0.001). On multivariate Cox regression analysis, the preablation M/H ratio (HR:
      1.20, 95% CI: 1.15-1.25, P < 0.001), left atrial diameter, duration of AF
      history, and early AF recurrence were independent predictors of AF recurrence.
      Using a cut-off level of 11.48, the pre-ablation M/H ratio predicted AF
      recurrence during follow-up with a sensitivity of 85% and a specificity of 74%.
      CONCLUSION: Elevated pre-ablation M/H ratio was associated with an increased
      recurrence of AF after cryoballoon-based catheter ablation. Our results support
      the role of pre-ablation pro-inflammatory and pro-oxidant environment in AF
      recurrence after ablation therapy but suggest that other factors are also
      important.

PMID- 25995389
TI  - One-year clinical outcome after pulmonary vein isolation in persistent atrial
      fibrillation using the second-generation 28 mm cryoballoon: a retrospective
      analysis.
AB  - AIMS: The purpose of this study was to determine efficacy of pulmonary vein
      isolation (PVI) using the 28 mm cryoballoon (CB) in patients with persistent
      atrial fibrillation (AF). Superior acute and 1-year outcome has been demonstrated
      following PVI, using the second-generation CB in patients with paroxysmal AF.
      Data on the outcome in patients with persistent AF are sparse. METHODS AND
      RESULTS: Forty-nine patients (20 female, mean age 63 +/- 10 years, mean left
      atrial diameter 46 +/- 5 mm) with persistent AF [median AF duration since first
      diagnosis: 48 (20:192) months] underwent second-generation 28 mm CB-based PVI.
      The freeze cycle duration was set at 240 s. After successful PVI, a bonus freeze
      cycle of 240 s was applied in the first 11/49 (22%) patients, and no bonus freeze
      cycle was used in the remaining 38/49 (78%) patients. Follow-up (FU) was based on
      outpatient clinic visits at 3, 6, and 12 months, which included Holter
      electrocardiograms and telephone interviews. Recurrence was defined as an episode
      of symptomatic and/or documented atrial tachyarrhythmia >30 s beyond the 3-month
      blanking period. A total of 193 pulmonary veins (PVs) were identified and 193/193
      (100%) PVs were successfully isolated. No phrenic nerve paralysis occurred.
      Follow-up was obtained in 49/49 (100%) patients with a mean FU duration of 416 +/
      178 days. After the 3-month blanking period, antiarrhythmic medication was
      discontinued in 33/49 (67%) patients. Thirty-four of 49 (69%) patients remained
      in stable sinus rhythm. CONCLUSIONS: In patients with persistent AF, use of the
      second-generation 28 mm CB was associated with a 69% 1-year clinical success
      rate.

PMID- 25995390
TI  - Ventricular arrhythmias in aortic valve stenosis before and after transcatheter
      aortic valve implantation.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) is a therapeutic treatment
      for patients with severe aortic stenosis (AS) at high surgical risk. Although the
      procedure is associated with a reduction in total mortality, there are no data
      regarding changing in the incidence of premature ventricular contractions (PVCs)
      and ventricular arrhythmias (VAs) after TAVI. The aim of this study was to assess
      the incidence of VAs before and after TAVI. METHODS AND RESULTS: We enrolled 237
      patients who underwent TAVI at our centre. Ninety-one patients were excluded for
      the following reasons: presence of prior permanent pacemaker (PPM) (n = 20), new
      PPM implant after TAVI (n = 48), death during the follow-up period (n = 16), and
      lost at follow-up (n = 7). Finally, 146 patients were included in our analysis.
      The presence of VAs was evaluated in all patients recording a 24 h Holter
      monitoring before the procedure and after 1 and 12 months. Ventricular
      arrhythmias were classified according to a modified Lown grading system. Before
      the procedure, isolates PVCs (grade 1-2 of Lown grading system) were present in
      34.9% of patients (n = 51). Complex PVCs (grade 3-4a-4b of Lown grading system)
      were present in 48.6% of the population (multifocal PVCs in 32 patients, 21.9%;
      pairs in 25 patients, 17.1%; ventricular tachycardia in 14 patients, 9.6%). One
      month after the procedure, we observed statistically significant incidence
      decrease of arrhythmias of grade 3 (from 21.9 to 17.1%) and grade 4 (pairs from
      17.1 to 12.3%; ventricular tachycardia from 9.6 to 4.8%). After 12 months, there
      was a further significant reduction in the frequency and severity of PVCs. In
      particular, 45.8% of patients had isolates PVCs (<30 in all given hours of
      monitoring in 45 patients, 30.8%; higher than 30 in any hour of monitoring in 22
      patients, 15%) while the frequency of complex arrhythmias was reduced to 16.4%
      (multifocal PVCs in 13 patients, 9%; couplets 8 patients, 5.5% and ventricular
      tachycardia in 3 patients, 2.0%). The difference was statistically significant (P
      < 0.01). CONCLUSION: This study indicates that VAs are common in patients with
      AS. We observed a significant decrease in the incidence and severity of PVCs
      since the first month after TAVI. Furthermore, after 1 year follow-up there was a
      further and significant reduction in the frequency of complex PVCs. This may be
      related to the benefits determined by valve replacement on left ventricular
      function.

PMID- 25995391
TI  - Effective reduction of fluoroscopy duration by using an advanced electroanatomic
      mapping system and a standardized procedural protocol for ablation of atrial
      fibrillation: 'the unleaded study'.
AB  - AIMS: It is recommended to keep exposure to ionizing radiation as low as
      reasonably achievable. The aim of this study was to determine whether fluoroscopy
      free mapping and ablation using a standardized procedural protocol is feasible in
      patients undergoing pulmonary vein isolation (PVI). METHODS AND RESULTS: Sixty
      consecutive patients were analysed: Thirty consecutive patients undergoing PVI
      using Carto3 were treated using a standardized procedural fluoroscopy protocol
      with X-ray being disabled after transseptal puncture (Group 1) and compared with
      a set of previous 30 consecutive patients undergoing PVI without a specific
      recommendation regarding the use of fluoroscopy (Group 2). The main outcome
      measures were the feasibility of fluoroscopy-free mapping and ablation, total
      fluoroscopy time, total dose area product (DAP), and procedure time. Sixty
      patients (age 60 +/- 10 years, 73% male, ejection fraction 0.55 +/- 0.09, left
      atrium 42 +/- 8 mm) were included. In Group 1, total fluoroscopy time was 4.2
      (2.6-5.6) min and mapping and ablation during PVI without using fluoroscopy was
      feasible in 29 of 30 patients (97%). In Group 2, total fluoroscopy time was 9.3
      (6.4-13.9) min (P < 0.001). Total DAP was 13.2 (6.2-22.2) Gy*cm(2) in Group 1
      compared with 17.5 (11.7-29.7) Gy*cm(2) in Group 2 (P = 0.036). Total procedure
      time did not differ between Groups 1 (133 +/- 37 min) and 2 (134 +/- 37 min, P =
      0.884). CONCLUSION: Performing mapping and ablation guided by an electroanatomic
      mapping system during PVI without using fluoroscopy after transseptal puncture
      using a standardized procedural protocol is feasible in almost all patients and
      is associated with markedly decreased total fluoroscopy duration and DAP.

PMID- 25995392
TI  - Risk of gastrointestinal adverse effects of dabigatran compared with warfarin
      among patients with atrial fibrillation: a nationwide cohort study.
AB  - AIMS: To examine the risk of gastrointestinal adverse effects associated with
      dabigatran use compared with warfarin among patients with atrial fibrillation
      (AF). METHODS AND RESULTS: Patients with AF and no history of gastrointestinal
      diseases initiating dabigatran or warfarin were identified from Danish nationwide
      registries from 22 August 2011 until 31 December 2012. Patients were classified
      as naive or experienced users, according to prior use of oral anticoagulant (OAC)
      therapy. The risk of subsequent proton pump inhibitor (PPI) use, upper dyspepsia
      like diagnoses (gastroesophageal reflux, gastritis, gastric, and duodenal ulcer)
      and gastrointestinal bleeding requiring hospitalization, gastroscopy, and
      discontinuation of dabigatran and warfarin was examined by cumulative incidence
      rates and multivariable adjusted Cox regression models. We identified five
      groups: OAC-naive warfarin (n = 4534); OAC-naive dabigatran 110 mg b.i.d.
      (dabigatran 110) (n = 1168); OAC-naive dabigatran 150 mg b.i.d. (dabigatran 150)
      (n = 1844); OAC-experienced dabigatran 110 (n = 1143); and OAC-experienced
      dabigatran 150 (n = 1748). Compared with OAC-naive warfarin, the rate of
      initiating PPIs was significantly increased for OAC-naive dabigatran 110 [hazard
      ratio (HR), 1.24; 95% confidence interval (CI), 1.02-1.50]. Other dabigatran
      regimes were not associated with a higher risk of initiating PPIs, upper
      dyspepsia-like diagnoses, gastrointestinal bleeding, or gastroscopy. The risk of
      discontinuation was increased for OAC-experienced dabigatran 150 (HR, 1.13; 95%
      CI, 1.02-1.25), but not for the other dabigatran-treated groups, relative to OAC
      naive warfarin. CONCLUSION: Dabigatran was not associated with upper dyspepsia
      like diagnoses or gastrointestinal bleeding requiring hospitalization, and
      gastroscopy. The risk of subsequent PPI use was increased for OAC-naive
      dabigatran 110 mg users, and the risk of discontinuation was increased for OAC
      experienced dabigatran 150 mg users.

PMID- 25995393
TI  - Intrathoracic pressure swings induced by simulated obstructive sleep apnoea
      promote arrhythmias in paroxysmal atrial fibrillation.
AB  - AIMS: There is preliminary evidence for a link between obstructive sleep apnoea
      (OSA) and arrhythmias such as paroxysmal atrial fibrillation (PAF) and sudden
      cardiac death but underlying mechanisms remain largely unknown. METHODS AND
      RESULTS: In this interventional crossover study, we evaluated whether
      intrathoracic pressure changes, induced by simulated OSA, trigger premature
      cardiac beats, and alter measures of ventricular repolarization [QTc and Tpeak-to
      Tend (TpTec) intervals] in patients with PAF. 12-Lead-electrocardiograms were
      recorded continuously in 44 patients, while simulating obstructive apnoea
      (Mueller manoeuvre, MM), obstructive hypopnoea (inspiration through a threshold
      load, ITH), end-expiratory central apnoea (AP), and during normal breathing (NB)
      in randomized order. The prevalence of OSA in these 44 patients was assessed by a
      sleep study. Atrial premature beats (APBs) occurred more frequently during MM
      (55% of patients) and ITH (32%), but not during AP (14%), compared with NB (9%)
      (P < 0.001, P = 0.006 and P = 0.688, respectively). Mueller manoeuvre led to a
      significant prolongation of QTc and TpTec intervals (+17.3 ms, P < 0.001 and +4.3
      ms, P = 0.005). Inspiration through a threshold load significantly increased QTc
      (+9.6 ms, P < 0.001) but not TpTec. End-expiratory central apnoea did not alter
      QTc and TpTec intervals. According to the sleep study, 56% of patients had OSA
      (apnoea hypopnoea index >=5). CONCLUSION: Simulated OSA induces APBs which may be
      important in patients with PAF, because the majority of episodes of PAF has been
      shown to be triggered by APBs. Simulated OSA leads to a significant prolongation
      of ventricular repolarization.

PMID- 25995394
TI  - Clinical performance of a new bidirectional rotational mechanical lead extraction
      sheath.
AB  - AIMS: We investigated the safety and efficacy of a new bidirectional rotational
      mechanical extraction sheath (Evolution RL, Cook Medical, USA). METHODS AND
      RESULTS: From April 2013 until September 2014, we performed lead extraction
      procedures in 71 patients with 112 leads scheduled for extraction. During this
      time period, we used the new Evolution RL rotational sheath in 40 patients on 52
      leads (24 pacemaker leads and 28 implantable cardioverter-defibrillator leads)
      scheduled for extraction. The mean lead implant duration in these patients was
      100.2 (22-271) months. Forty leads were right ventricular leads, 10 right atrial
      leads, and 2 coronary sinus leads. Clinical success among the leads approached
      with the Evolution RL device was 98.1%. Operative mortality was zero. Major
      complications did not occur. Four minor complications were encountered (all
      pocket haematomas). No device-related complications were noted. In cases with
      multiple leads in situ, no wrapping of companion leads was seen. The average
      number of extraction tools used per lead was 2.4 (2-4) in the Evolution RL
      cohort. CONCLUSION: Based on the presented results of our initial experience with
      the new bidirectional rotational mechanical extraction device, its use is safe
      and efficient with high success rates in long implanted leads.

PMID- 25995395
TI  - Antitachycardia pacing for termination of ventricular tachyarrhythmias: should we
      use it?

PMID- 25995396
TI  - Management of paediatric arrhythmias in Europe: authors' reply.

PMID- 25995397
TI  - Relationship between Mediterranean diet and time in therapeutic range in atrial
      fibrillation patients taking vitamin K antagonists.
AB  - AIMS: It is unclear if atrial fibrillation (AF) patients treated with oral
      vitamin K antagonists (VKAs) must follow a specific diet to avoid interference
      with anticoagulation. The aim of this study was to assess if Mediterranean diet
      (Med-Diet) may affect quality of anticoagulation, as expressed by the time in
      therapeutic range (TTR). METHODS AND RESULTS: A prospective observational study
      including 553 non-valvular AF patients. Time in therapeutic range was calculated
      for all patients treated with VKAs, and adherence to Med-Diet was evaluated with
      a validated nine-item dietary questionnaire. Cardiovascular events (CVEs), such
      as cardiovascular death and fatal/non-fatal stroke or myocardial infarction, and
      bleedings were recorded. The median follow-up was 31.6 months. The median number
      of international normalized ratios for each patient was 63.0 (35.0-98.0) and 38
      730 blood samples were analysed. In the whole cohort, the mean TTR was 65.5 +/-
      17.8%. The mean Med-Diet score was 5.19 +/- 1.6, with frequent use of olive oil
      (90.1%), fruits (88.4%), and vegetables (69.3%) and low meat intake (71.2%).
      There were no differences among tertiles of Med-Diet score regarding TTR. A
      multivariable linear regression analysis showed that diabetes (beta: -0.105, P =
      0.015) and the use of angiotensin converting enzyme inhibitor/angiotensin
      receptor blockers (beta: 0.153, P < 0.001) were associated with TTR. Compared
      with those without, AF patients with a CVE had significantly lower TTR (65.9 +/-
      17.9 vs. 59.6 +/- 15.9, P = 0.029) and Med-Diet score (5.2 +/- 1.5 vs. 4.4 +/-
      1.9, P = 0.004). A reduction of CVE was observed for each point of the Med-Diet
      score (hazard ratio 0.790, P = 0.017). CONCLUSION: In our cohort of AF patients,
      Med-Diet is not associated with changes in TTR, and thus can be recommended for
      AF patients who are taking VKAs.

PMID- 25995398
TI  - Management of paediatric arrhythmias in Europe.

PMID- 25995399
TI  - Atrial standstill in sinus node disease due to extensive atrial fibrosis: impact
      on dual chamber pacemaker implantation.
AB  - AIMS: Atrial standstill is characterized by the absence of atrial activity. We
      report about a series of cases, in which conventional atrial pacemaker lead
      implantation in patients with symptomatic sinus node disease failed due to lack
      of excitable right atrial tissue, thus, prompting the diagnosis of atrial
      standstill. We hypothesized that mapping of the atria with subsequent
      identification of myocardium still amenable to atrial pacing would allow dual
      chamber pacemaker implantation. METHODS AND RESULTS: In four patients, atrial
      lead implantation failed. In these patients, spontaneous or fibrillatory
      electrical activity was absent but the atria could not be captured despite high
      stimulation voltages at conventional atrial sites. We suspected partial or
      complete atrial standstill and subsequently confirmed this hypothesis by
      conventional (n = 1) or electroanatomical mapping (n = 3). Areas of fibrotic
      tissue were present in all patients as identified by lack of spontaneous
      electrical activity and inability of local electrical capture via the mapping
      catheter. Surviving atrial tissue, which could be electrically captured with
      subsequent conduction of activity to the atrioventricular (AV) node, was present
      in three patients. Successful targeted atrial lead implantation at these sites
      was achieved in all these patients. Isolated sinus node activity without
      conduction to the atria was found in one patient. CONCLUSION: Partial atrial
      standstill may be present and prevent atrial lead implantation in patients with
      sinus node disease. In these patients, recognition of partial atrial standstill
      and identification of surviving muscular islets with connection to the AV node by
      mapping studies may still allow synchronous AV sequential pacing.

PMID- 25995400
TI  - Manipulation of projection approach in pediatric radiography.
AB  - PURPOSE: To determine whether manipulating routine projections from
      anteroposterior (AP) to posteroanterior (PA) during projection radiography
      studies will result in reduced pediatric radiation exposure. METHOD: A literature
      analysis was conducted on pediatric radiation exposure, radiation protection, and
      tissue weighting factors. Multiple quantitative datasets were used to support
      findings related to projection manipulation. RESULTS: Dosimetric studies confirm
      that the PA projection significantly decreases radiation exposure to nearly all
      radiosensitive tissue, with the exception of the patient's bone marrow.
      DISCUSSION: Pediatric patients are inherently more sensitive to ionizing
      radiation, making this patient population a major focus of dose-reduction issues.
      Radiologic technologists are charged with keeping dose as low as reasonably
      achievable (following the ALARA principle), and performing PA projections rather
      than routine AP projections might decrease radiation to the pediatric population.
      CONCLUSION: The PA projection results in a definitive reduction in radiation
      exposure to the majority of radiosensitive organs and tissues and should be
      considered for implementation on a routine basis.

PMID- 25995401
TI  - Using mobile electronic devices to deliver educational resources in developing
      countries.
AB  - BACKGROUND: Developing countries have far fewer trained radiography professionals
      than developed countries, which exacerbates the limited access to imaging
      services. The lack of trained radiographers reflects, in part, limited
      availability of radiographer-specific educational resources. Historically,
      organizations that provided such resources in the developing world faced
      challenges related to the limited stock of current materials as well as expenses
      associated with shipping and delivery. METHODS: Four mobile electronic devices
      (MEDs) were loaded with educational content (e-books, PDFs, and digital
      applications) spanning major radiography topics. The MEDs were distributed to 4
      imaging departments in Ghana, India, Nepal, and Nigeria based on evidence of need
      for radiography-specific resources, as revealed by survey responses. A cost
      comparison of postal delivery vs digital delivery of educational content was
      performed. The effectiveness of delivering additional content via Wi-Fi
      transmission also was evaluated. Feedback was solicited on users' experience with
      the MEDs as a delivery tool for educational content. RESULTS: An initial average
      per e-book expense of $30.05, which included the cost of the device, was
      calculated for the MED delivery method compared with $15.56 for postal delivery
      of printed materials. The cost of the MED delivery method was reduced to an
      average of $10.05 for subsequent e-book deliveries. Additional content was
      successfully delivered via Wi-Fi transmission to all recipients during the 3
      month follow-up period. Overall user feedback on the experience was positive, and
      ideas for enhancing the MED-based method were identified. CONCLUSION: Using MEDs
      to deliver radiography-specific educational content appears to be more cost
      effective than postal delivery of printed materials on a long-term basis. MEDs
      are more efficient for providing updates to educational materials. Customization
      of content to department needs, and using projector devices could enhance the
      usefulness of MEDs for radiographer training.

PMID- 25995402
TI  - Preoperative Breast MR Imaging: Its Role in Surgical Planning.
AB  - PURPOSE: To explore the role and usefulness of preoperative breast magnetic
      resonance (MR) imaging in surgical planning and to determine whether routine use
      of preoperative breast MR imaging benefits patients. METHODS: Searches were
      conducted to locate literature, specifically clinical studies, discussing the
      effect preoperative breast MR imaging has on altering surgical plans. Selected
      articles encompassed topics including additional biopsies, wider excisions,
      mastectomies, and re-excisions. The results of these studies were examined for
      the purpose of supporting or refuting the notion that preoperative MR imaging is
      beneficial. RESULTS: Consensus is lacking about the role of preoperative MR
      imaging in surgical planning for patients with breast cancer. Some studies
      support the use of the technique, while others do not. DISCUSSION: Preoperative
      breast MR imaging influences surgical planning for patients with breast cancer.
      When used before surgery, MR imaging can lead to changes in the surgical plan.
      Changes include additional biopsies, a more extensive lumpectomy, or the
      potential for a mastectomy. Certain research studies conclude that MR imaging
      improves surgical planning, while others disagree. CONCLUSION: The current
      available literature does not reach a sole conclusion. Some studies suggest that
      MR imaging is beneficial, while others declare that it leads to unnecessary
      surgical changes. Additional studies do not reach a decision either way and
      instead call for further research. The lack of consensus indicates that more
      research is needed before the usefulness of breast MR imaging for surgical
      planning can be determined.

PMID- 25995403
TI  - Radiation protection education in fluoroscopy.
AB  - Potential biological damage from radiation received during fluoroscopy procedures
      is of particular concern because of the high volume and variety of procedures
      performed and the increasing length of radiation exposure. This article focuses
      on the effects of low-level radiation, gaps in education and skills among
      personnel performing and assisting with fluoroscopy, the certification and
      privileging of fluoroscopy personnel, and compliance with radiation protection
      practices. 

PMID- 25995404
TI  - Meditation, stress relief, and well-being.
AB  - As the pace of life increases, stress is becoming endemic, and in the radiologic
      sciences, stress is keenly felt by technologists and patients. Meditation, a
      potential remedy to stress, is the subject of an increasing number of medical
      studies that often rely upon radiologic imaging scans to determine the
      physiological effects of meditation on brain activity. A wide range of meditation
      techniques have beneficial effects on the mind, body, and emotions. Radiologic
      technologists might find that meditation improves their quality of life as well
      as their level of job satisfaction, allowing them to provide improved quality of
      care to their patients. 

PMID- 25995405
TI  - New software application assesses lung tissue damage.

PMID- 25995406
TI  - Brain imaging studies can help educators.

PMID- 25995407
TI  - Left ventricular true aneurysm following myocardial infarction.

PMID- 25995408
TI  - Addressing magnetic resonance safety using a modified preoperative time-out
      approach.

PMID- 25995409
TI  - Teaching trauma radiography.

PMID- 25995410
TI  - Guidelines for conducting responsible research.

PMID- 25995411
TI  - A challenging diagnosis.

PMID- 25995412
TI  - Temporal Bone CT: Anatomy, Technique, and Associated Pathophysiology.
AB  - Computed tomography (CT) of the temporal bone is performed to evaluate trauma,
      tumors, sinuses, the skull base, or otic structures. This article discusses
      temporal bone anatomy and reviews CT technique for a temporal bone examination.
      Some conditions associated with temporal bone examinations, auditory symptoms,
      and postoperative changes also are discussed. 

PMID- 25995413
TI  - Breast intervention and breast cancer treatment options.
AB  - Breast cancer is the second leading cause of death among women in the United
      States. Although controversy has emerged in recent years regarding the diagnosis
      and treatment of this disease, it remains important to detect and treat breast
      cancer before it has metastasized. This article provides an overview of breast
      biopsy techniques, biopsy specimen imaging, and treatment options for breast
      cancer patients, including surgery, radiation therapy, chemotherapy, and
      molecular treatments. Finally, breast reconstruction options are presented. 

PMID- 25995414
TI  - 20 years of advancing the standard of cancer care.

PMID- 25995416
TI  - NCCN: 20 Years of Improving Patients' Lives.
AB  - In his Keynote Address at the NCCN 20th Annual Conference, Robert W. Carlson, MD,
      reflected on the achievements of NCCN and described how the organization will
      continue to grow under his leadership. Recognizing that the founding of NCCN was
      by a group of visionary leaders who came together 20 years ago to assure access
      of patients to high-quality cancer care, Dr. Carlson said "All our efforts within
      NCCN are focused on improving the quality, effectiveness, and efficiency of
      patient care, so that our patients can live better lives." 

PMID- 25995417
TI  - NCCN Roundtable: What Are the Characteristics of an Optimal Clinical Practice
      Guideline?
AB  - Much has changed in the treatment of cancer since the first NCCN Clinical
      Practice Guidelines in Oncology (NCCN Guidelines) were rolled out for 8 different
      tumor types in November 1996. NCCN Guidelines now include involved algorithms
      often containing multiple treatment alternatives and detailed pathways of care
      that depend on more-specific patient characteristics and molecular tumor
      diagnostics. With 47 different individual NCCN panels, all members of the cancer
      care team are now better informed than ever to guide patients through the often
      complex decision-making required to improve the odds of successful outcomes. At
      the NCCN 20th Annual Conference, a distinguished panel assembled to take a closer
      look at these invaluable clinical practice guidelines, first glancing backward to
      how it all started and then forward to explore the key ingredients of trustworthy
      guidelines. 

PMID- 25995418
TI  - New NCCN Guidelines: Smoking Cessation for Patients With Cancer.
AB  - Even after a cancer diagnosis, for any stage and prognosis, patients with cancer
      can reap health benefits from smoking cessation. To address the clinical problems
      associated with smoking in cancer patients, the NCCN created a new set of NCCN
      Clinical Practice Guidelines in Oncology (NCCN Guidelines) for 2015. At NCCN 20th
      Annual Conference, Dr. Peter Shields presented these inaugural guidelines,
      focusing primarily on the adverse outcomes associated with smoking in patients
      with cancer, the common barriers to smoking cessation in this patient population,
      simple yet effective assessment approaches, and treatment recommendations that
      center on the combination of pharmacotherapy and behavioral therapy. 

PMID- 25995419
TI  - Toward less-invasive management of early-stage breast cancer.
AB  - Patients with early-stage breast cancer today are benefitting from a growing
      trend toward less-invasive disease staging and management. This is occurring as a
      result of molecular profiling to refine treatment, surgical approaches that
      improve cosmesis, radiotherapy approaches that are more convenient and less
      likely to produce toxicity, and the discontinuation of routine axillary
      dissection. Less-aggressive treatments yield better quality of life, which is
      very important in a malignancy with excellent long-term outcomes. 

PMID- 25995420
TI  - Optimizing Treatment of HER2-Positive Breast Cancer.
AB  - The treatment of HER2-positive breast cancer has benefited from a number of
      targeted agents. Although adjuvant trastuzumab has dramatically reduced
      progression--making metastatic disease far less common today--newer treatment
      advances are also impacting this disease. Dual targeting with pertuzumab and
      trastuzumab can extend the survival of metastatic disease by more 16 months, but
      despite such success, resistance to HER2 targeting remains a challenge. Drugs in
      the pipeline, such as neratinib, may help meet this therapeutic demand. In
      addition to anti-HER2 agents, chemotherapy is beneficial to patients with tumors
      1 cm or larger, but the optimal treatment of smaller tumors is still a work in
      progress.

PMID- 25995421
TI  - Evolving treatment strategies for triple-negative breast cancer.
AB  - Although not yet practice changing in early-stage triple-negative breast cancer,
      growing evidence suggests that neoadjuvant platinum-based therapy is active and
      that some patients may benefit from such an approach. Recent randomized phase III
      data suggests that carboplatin has comparable efficacy to docetaxel as first-line
      therapy in unselected advanced triple-negative breast cancer. In both settings,
      the efficacy of such treatment appears to be influenced by BRCA1/2 mutation
      status, with carriers of these mutations experiencing higher response rates. To
      optimize patient selection, biomarkers of response need to be incorporated into
      randomized clinical trials and validated. In addition to BRCA1/2, it is likely
      that measures of genomic instability and other germline biomarkers beyond BRCA1/2
      may be associated with therapeutic sensitivity. 

PMID- 25995422
TI  - Advanced hormone-sensitive breast cancer: overcoming resistance.
AB  - Novel strategies to overcome resistance to endocrine therapy are on the horizon,
      especially PI3K inhibitors, CDK 4/6 inhibitors, and agents targeting methylation.
      However, many, if not most, patients with progressive estrogen receptor-positive
      breast cancer will continue to show response to multiples lines of endocrine
      therapy alone. Which patient subsets will be candidates for the emerging agents
      is still unclear, but in the future, subtype of the tumor, mutational status, and
      treatment goals will be part of the equation. Always, it will be necessary to
      individualize treatment. 

PMID- 25995423
TI  - NCCN Roundtable:Value-Based Decision-Making at the Bedside.
AB  - As part of the NCCN 20th Annual Conference: Advancing the Standard of Cancer
      Care, a distinguished and diverse group of experts on value-based decision-making
      in oncology discussed guidelines and pathways and how their use has impacted
      bedside evidence-based decision-making for both physicians and patients.
      Moderated by Clifford Goodman, PhD, the roundtable also reflected on the criteria
      used to assess shared decision-making and the relationship between outcomes and
      cost when determining value. 

PMID- 25995424
TI  - Updates to the management of chronic lymphocytic leukemia.
AB  - The decision of when to start treatment for patients with chronic lymphocytic
      leukemia (CLL) has not markedly changed; it is triggered by parameters of active
      disease, such as progressive symptoms or progressive cytopenias related to bone
      marrow compromise from disease. How to treat patients with CLL has become less
      complicated, given the growing list of options for CLL, and generally depends on
      the patient's age, presence of comorbidities, and risk factors (such as
      chromosome 17 or 11 deletion). During his presentation at the NCCN 20th Annual
      Conference, Dr. William Wierda focused attention on many of the new kids on the
      therapeutic block for CLL--the CD20 monoclonal antibodies obinutuzumab and
      ofatumumab, the BTK inhibitor ibrutinib, the PI3K inhibitor idelalisib, and the
      BCL-2 inhibitor venetoclax--and reviewed some of the clinical data supporting the
      use of these agents in different patient populations with CLL.

PMID- 25995425
TI  - Emerging treatment options for B-cell lymphomas.
AB  - As targeted therapy in B-cell lymphomas rapidly expands beyond anti-CD20
      monoclonal antibodies, many newer types of agents are in various stages of
      development. During his presentation at the NCCN 20th Annual Conference, Dr.
      Andrew D. Zelenetz explored many of them, including the newer immunoconjugates,
      the Bruton's tyrosine kinase inhibitor ibrutinib, agents targeting apoptosis such
      as venetoclax (ABT-199), the immunomodulator lenalidomide, and novel immune
      checkpoint inhibitors such as nivolumab. To improve outcomes in patients with B
      cell lymphomas, these therapies either target the tumor cells and their pathways
      or focus on the microenvironment and immune modulation. 

PMID- 25995426
TI  - Principles of immunotherapy.
AB  - With recent success stories in melanoma, breast cancer, gastric cancer, renal
      cell carcinoma, prostate cancer, Hodgkin's lymphoma, squamous cell lung cancer,
      and other malignancies, immunotherapy has emerged as perhaps the most paradigm
      changing treatment strategy to occur on the oncologic front in the last 35 years.
      At the NCCN 20th Annual Conference, Dr. Anthony J. Olszanski offered a primer on
      immunotherapeutic basics, featuring the complex interplay between the immune
      system and cancer; a comparative look at innate and adaptive immunity; and the
      topics of immune surveillance, tumor escape mechanisms, and immune suppression.
      Several examples of cancer immunotherapies in action are briefly presented. 

PMID- 25995427
TI  - Treatment options expanding for advanced melanoma.
AB  - Immunotherapies and BRAF and MEK inhibitors have dramatically improved outcomes
      in advanced melanoma. The availability of these novel approaches has necessitated
      changes to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).
      The NCCN Guidelines feature algorithms that aid clinicians in selecting initial
      therapy, which now includes anti-programmed death protein receptor-1 PD-1
      inhibitors among the recommended systemic therapy options for patients with
      metastatic or unresectable disease. 

PMID- 25995428
TI  - Targeted/emerging therapies for metastatic non-small cell lung cancer.
AB  - At one time, histology alone guided treatment decisions in non-small cell lung
      cancer (NSCLC), but now molecular diagnostics help to categorize patients with
      lung cancer by driver mutations. This additional information arms oncologists
      with the keys to selecting the right targeted agent with the best chance of
      success for different subgroups of patients with NSCLC. During her presentation
      at the NCCN 20th Annual Conference, Dr. Leora Horn focused attention on both
      approved and emerging therapies in metastatic disease that target an assortment
      of molecular subsets, such as EGFR mutations, ALK rearrangements, ROS1
      rearrangements, and BRAF mutations. 

PMID- 25995429
TI  - Kidney cancer: current and novel treatment options.
AB  - Antiangiogenic therapies remain the standard of care in the front-line setting
      for renal cell carcinoma, although vascular endothelial growth factor (VEGF)
      blockade is not sufficient, and many patients do not respond to such treatment.
      With a host of approved agents, questions arise as to how best to use them in
      both initial and secondary treatments. Optimal sequences are currently being
      tested in various clinical trials. Because approximately 20% of patients
      exhibiting primary resistance to these anti-VEGF therapies, new therapies are
      needed. Novel therapies such as MET and AXL inhibitors as well as checkpoint
      antibodies hold promise for the future. 

PMID- 25995430
TI  - Optimizing systemic therapy selection in metastatic colorectal cancer.
AB  - For metastatic colorectal cancer, many effective agents can be incorporated into
      multiple lines of therapy across the nearly 3-year continuum of treatment.
      Emphasis should be on using all the recommended agents, with extended duration of
      anti-vascular endothelial growth factor treatment, and on identifying patients
      with any mutation in the RAS pathway. Chemotherapy plus bevacizumab or an
      epidermal growth factor receptor antibody are both viable options as first-line
      therapy in patients with RAS wild-type disease. 

PMID- 25995431
TI  - Management of dermatologic toxicities.
AB  - Dermatologic toxicities related to cancer therapies have become even more common
      with the use of targeted treatments. A proactive approach is necessary to reduce
      the pain and suffering these patients experience. The oncologist should become
      comfortable in preventing and managing these complications to keep patients on
      optimal drugs and doses. At the NCCN 20th Annual Conference, Dr. Mario E.
      Lacouture advised clinicians on appropriate strategies to manage rash,
      paronychia, alopecia, and other dermatologic conditions frequently seen in
      patients with cancer. 

PMID- 25995432
TI  - New treatment options in castration-resistant prostate cancer.
AB  - Most of the updates in the 2015 NCCN Clinical Practice Guidelines in Oncology
      (NCCN Guidelines) for Prostate Cancer center on the systemic therapy front, with
      a host of newer agents in the mix. At the NCCN 20th Annual Conference, Dr. Andrew
      J. Armstrong discussed some of the key developments in metastatic castration
      resistant and castration-sensitive prostate cancer, particularly the conflicting
      results on repurposing docetaxel in castration-sensitive disease, the specific
      population who may experience greater survival benefit from immunotherapy in
      castration-resistant disease, updated data on the use of androgen receptor and
      biosynthesis inhibitors, and the emerging role of AR-V7 (androgen-receptor splice
      variant 7 messenger RNA) as a biomarker of treatment response. 

PMID- 25995433
TI  - Multiple myeloma: new uses for available agents, excitement for the future.
AB  - With the availability of a new proteasome inhibitor, carfilzomib, and a new
      immunomodulatory drug, pomalidomide, the treatment of multiple myeloma has become
      more effective. The updated NCCN Clinical Practice Guidelines in Oncology for
      Multiple Myeloma provide new recommendations for use of carfilzomib and
      pomalidomide. As new classes of drugs such as monoclonal antibodies become
      available, the treatment landscape will be rendered even brighter. 

PMID- 25995434
TI  - Treatment milestones in chronic myelogenous leukemia: stay the course or change
      therapy?
AB  - The success of various generations of tyrosine kinase inhibitors in chronic
      myelogenous leukemia (CML) is well-known, with many patients experiencing long
      term benefits from treatment. However, not every patient with CML can tolerate
      this therapy, shows response to initial treatment, or avoids disease progression
      or drug resistance. During his presentation at the NCCN 20th Annual Conference,
      Jerald Radich, MD, shared his thoughts and some supportive data on the critical
      role of monitoring response at 3 months, the often-neglected yet key issue of
      patient adherence to therapy, the recommended timing for mutational analysis, and
      the pressing need to prevent patients from going from chronic-phase disease into
      accelerated phase/blast crisis. 

PMID- 25995435
TI  - Multidisciplinary management of pancreatic cancer.
AB  - Pancreatic cancer remains a vexing treatment challenge, with a cure rate that
      remains just 7%. Two effective regimens--gemcitabine/nab-paclitaxel and
      FOLFIRINOX--have improved outcomes and are being used earlier in the disease.
      However, meaningful differences in outcomes may not be realized without novel
      strategies. Targeting of the immune system is an active area of research.

PMID- 25995436
TI  - 23814, an Inhibitory Antibody of Ligand-Mediated Notch1 Activation, Modulates
      Angiogenesis and Inhibits Tumor Growth without Gastrointestinal Toxicity.
AB  - Dysregulation of Notch signaling has been implicated in the development of many
      different types of cancer. Notch inhibitors are being tested in the clinic, but
      in most cases gastrointestinal and other toxicities have limited the dosage and,
      therefore, the effectiveness of these therapies. Herein, we describe the
      generation of a monoclonal antibody against the ligand-binding domain of the
      Notch1 receptor that specifically blocks ligand-induced activation. This
      antibody, 23814, recognizes both human and murine Notch1 with similar affinity,
      enabling examination of the effects on both tumor and host tissue in preclinical
      models. 23814 blocked Notch1 function in vivo, inhibited functional angiogenesis,
      and inhibited tumor growth without causing gastrointestinal toxicity. The lack of
      toxicity allowed for combination of 23814 and the VEGFR inhibitor tivozanib,
      resulting in significant growth inhibition of several VEGFR inhibitor-resistant
      tumor models. Analysis of the gene expression profiles of an extensive collection
      of murine breast tumors enabled the successful prediction of which tumors were
      most likely to respond to the combination of 23814 and tivozanib. Therefore, the
      use of a specific Notch1 antibody that does not induce significant toxicity may
      allow combination treatment with angiogenesis inhibitors or other targeted agents
      to achieve enhanced therapeutic benefit.

PMID- 25995438
TI  - The Myb-p300 Interaction Is a Novel Molecular Pharmacologic Target.

PMID- 25995437
TI  - The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)
      E1alpha Phosphorylation.
AB  - Inhibition of the PI3K/Akt pathway decreases hypoxia within SQ20B human head and
      neck cancer xenografts. We set out to understand the molecular mechanism
      underlying this observation. We measured oxygen consumption using both a Clark
      electrode and an extracellular flux analyzer. We made these measurements after
      various pharmacologic and genetic manipulations. Pharmacologic inhibition of the
      PI3K/mTOR pathway or genetic inhibition of Akt/PI3K decreased the oxygen
      consumption rate (OCR) in vitro in SQ20B and other cell lines by 30% to 40%.
      Pharmacologic inhibition of this pathway increased phosphorylation of the E1alpha
      subunit of the pyruvate dehydrogenase (PDH) complex on Ser293, which inhibits
      activity of this critical gatekeeper of mitochondrial respiration. Expressing
      wild-type PTEN in a doxycycline-inducible manner in a cell line with mutant PTEN
      led to an increase in PDH-E1alpha phosphorylation and a decrease in OCR.
      Pretreatment of SQ20B cells with dichloroacetate (DCA), which inhibits PDH
      E1alpha phosphorylation by inhibiting dehydrogenase kinases (PDK), reversed the
      decrease in OCR in response to PI3K/Akt/mTOR inhibition. Likewise, introduction
      of exogenous PDH-E1alpha that contains serine to alanine mutations, which can no
      longer be regulated by phosphorylation, also blunted the decrease in OCR seen
      with PI3K/mTOR inhibition. Our findings highlight an association between the
      PI3K/mTOR pathway and tumor cell oxygen consumption that is regulated in part by
      PDH phosphorylation. These results have important implications for understanding
      the effects of PI3K pathway activation in tumor metabolism and also in designing
      cancer therapy trials that use inhibitors of this pathway.

PMID- 25995439
TI  - The role of non-coding RNAs in male sex determination and differentiation.
AB  - A complex network of gene regulation and interaction drives male sex
      determination and differentiation. While many important protein-coding genes that
      are necessary for proper male development have been identified, many disorders in
      human sex development are still unexplained at the molecular level. This suggests
      that key factors and regulatory mechanisms are still unknown. In recent years,
      extensive data have shown that different classes of non-coding RNAs (ncRNAs) play
      a role in almost all developmental and physiological pathways. Here we review
      what is known about their role in male sex determination and differentiation not
      only in mammals, but also other species. While for some processes a key role for
      ncRNA has been identified, we are still far from having a complete picture. 

PMID- 25995440
TI  - Mitochondrial biogenesis and degradation are induced by CCCP treatment of porcine
      oocytes.
AB  - In this study, we investigated the mitochondrial quality control system in
      porcine oocytes during meiotic maturation. Cumulus cell oocyte complexes (COCs)
      collected from gilt ovaries were treated with 10  MUM carbonyl cyanide-m
      chlorophenylhydrazone (CCCP; a mitochondrial uncoupler) for 2  h. The CCCP
      treatment was found to significantly reduce ATP content, increase the amount of
      phosphorylated AMP-activated protein kinase and elevate reactive oxygen species
      levels in oocytes. When the CCCP-treated COCs were cultured further for 44  h in
      maturation medium, the ATP levels were restored and the parthenogenetic
      developmental rate of oocytes to the blastocyst stage was comparable with that of
      untreated COCs. To examine the effects of CCCP treatment of oocytes on the
      kinetics of mitochondrial DNA copy number (Mt number), COCs treated with 0 or 10 
      MUM CCCP were cultured for 44  h, after which the Mt number was determined by RT
      PCR. CCCP treatment was found to increase the Mt number in the modified
      maturation medium in which mitochondrial degradation was inhibited by MG132,
      whereas CCCP treatment did not affect the Mt number in the maturation medium
      lacking MG132. The relative gene expression of TFAM was furthermore shown to be
      significantly higher in CCCP-treated oocytes than in untreated oocytes. Taken
      together, the finding presented here suggest that when the mitochondria are
      injured, mitochondrial biogenesis and degradation are induced, and that these
      processes may contribute to the recuperation of oocytes.

PMID- 25995441
TI  - Expression and characterization of three Aurora kinase C splice variants found in
      human oocytes.
AB  - Chromosome segregation is an extensively choreographed process yet errors still
      occur frequently in female meiosis, leading to implantation failure, miscarriage
      or offspring with developmental disorders. Aurora kinase C (AURKC) is a component
      of the chromosome passenger complex and is highly expressed in gametes. Studies
      in mouse oocytes indicate that AURKC is required to regulate chromosome
      segregation during meiosis I; however, little is known about the functional
      significance of AURKC in human oocytes. Three splice variants of AURKC exist in
      testis tissue. To determine which splice variants human oocytes express, we
      performed quantitative real-time PCR using single oocytes and found expression of
      all three variants. To evaluate the functional differences between the variants,
      we created green fluorescent protein-tagged constructs of each variant to express
      in oocytes from Aurkc(-/-) mice. By quantifying metaphase chromosome alignment,
      cell cycle progression, phosphorylation of INCENP and microtubule attachments to
      kinetochores, we found that AURKC_v1 was the most capable of the variants at
      supporting metaphase I chromosome segregation. AURKC_v3 localized to chromosomes
      properly and supported cell cycle progression to metaphase II, but its inability
      to correct erroneous microtubule attachments to kinetochores meant that
      chromosome segregation was not as accurate compared with the other two variants.
      Finally, when we expressed the three variants simultaneously, error correction
      was more robust than when they were expressed on their own. Therefore, oocytes
      express three variants of AURKC that are not functionally equivalent in
      supporting meiosis, but fully complement meiosis when expressed simultaneously. 

PMID- 25995443
TI  - MicroRNA regulation of RAD51 in serous ovarian cancer modulates chemotherapy
      response.

PMID- 25995442
TI  - Augmentation of response to chemotherapy by microRNA-506 through regulation of
      RAD51 in serous ovarian cancers.
AB  - BACKGROUND: Chemoresistance is a major challenge in cancer treatment. miR-506 is
      a potent inhibitor of the epithelial-to-mesenchymal transition (EMT), which is
      also associated with chemoresistance. We characterized the role of miR-506 in
      chemotherapy response in high-grade serous ovarian cancers. METHODS: We used
      Kaplan-Meier and log-rank methods to analyze the relationship between miR-506 and
      progression-free and overall survival in The Cancer Genome Atlas (TCGA) (n = 468)
      and Bagnoli (n = 130) datasets, in vitro experiments to study whether miR-506 is
      associated with homologous recombination, and response to chemotherapy agents. We
      used an orthotopic ovarian cancer mouse model (n = 10 per group) to test the
      effect of miR-506 on cisplatin and PARP inhibitor sensitivity. All statistical
      tests were two-sided. RESULTS: MiR-506 was associated with better response to
      therapy and longer progression-free and overall survival in two independent
      epithelial ovarian cancer patient cohorts (PFS: high vs low miR-506 expression;
      Bagnoli: hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.90 to 4.70, P
      < .0001; TCGA: HR = 1.49, 95% CI = 1.00 to 2.25, P = 0.04). MiR-506 sensitized
      cells to DNA damage through directly targeting the double-strand DNA damage
      repair gene RAD51. Systemic delivery of miR-506 in 8-12 week old female athymic
      nude mice statistically significantly augmented the cisplatin and olaparib
      response (mean tumor weight +/- SD, control miRNA plus cisplatin vs miR-506 plus
      cisplatin: 0.36+/-0.05g vs 0.07+/-0.02g, P < .001; control miRNA plus olaparib vs
      miR-506 plus olaparib: 0.32+/-0.13g vs 0.05+/-0.02g, P = .045, respectively),
      thus recapitulating the clinical observation. CONCLUSIONS: MiR-506 is a robust
      clinical marker for chemotherapy response and survival in serous ovarian cancers
      and has important therapeutic value in sensitizing cancer cells to chemotherapy.

PMID- 25995444
TI  - Markers of Endothelial-to-Mesenchymal Transition: Evidence for Antibody
      Endothelium Interaction during Antibody-Mediated Rejection in Kidney Recipients.
AB  - Antibody-mediated rejection (ABMR) is a leading cause of allograft loss.
      Treatment efficacy depends on accurate diagnosis at an early stage. However,
      sensitive and reliable markers of antibody-endothelium interaction during ABMR
      are not available for routine use. Using immunohistochemistry, we retrospectively
      studied the diagnostic value of three markers of endothelial-to-mesenchymal
      transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53
      renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated
      rejection specimens, and nine normal grafts. We validated our results in an
      independent set of 74 unselected biopsy specimens. Endothelial cells of the
      peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat
      shock protein 47 strongly, whereas those from normal renal grafts did not. The
      level of EndMT marker expression was significantly associated with current ABMR
      criteria, including capillaritis, glomerulitis, peritubular capillary C4d
      deposition, and donor-specific antibodies. These markers allowed us to identify
      C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were
      more specific than capillaritis for the diagnosis and prognosis of ABMR and
      predicted late (up to 4 years after biopsy) renal graft dysfunction and
      proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT
      markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of
      85%. Fascin1 expression in peritubular capillaries was also induced in a rat
      model of ABMR. In conclusion, EndMT markers are a sensitive and reliable
      diagnostic tool for detecting endothelial activation during ABMR and predicting
      late loss of allograft function. 

PMID- 25995445
TI  - Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of
      mature ribosomes by enhancing production of shortened 5.8S rRNA.
AB  - Processing of rRNA during ribosome assembly can proceed through alternative
      pathways but it is unclear whether this could affect the structure of the
      ribosome. Here, we demonstrate that shortage of a ribosomal protein can change
      pre-rRNA processing in a way that over time alters ribosome diversity in the
      cell. Reducing the amount of Rpl17 in mouse cells led to stalled 60S subunit
      maturation, causing degradation of most of the synthesized precursors. A fraction
      of pre-60S subunits, however, were able to complete maturation, but with a 5'
      truncated 5.8S rRNA, which we named 5.8SC. The 5' exoribonuclease Xrn2 is
      involved in the generation of both 5.8S(C) and the canonical long form of 5.8S
      rRNA. Ribosomes containing 5.8S(C) rRNA are present in various mouse and human
      cells and engage in translation. These findings uncover a previously undescribed
      form of mammalian 5.8S rRNA and demonstrate that perturbations in ribosome
      assembly can be a source of heterogeneity in mature ribosomes.

PMID- 25995446
TI  - Profiling ribonucleotide modifications at full-transcriptome level: a step toward
      MS-based epitranscriptomics.
AB  - The elucidation of the biological significance of RNA post-transcriptional
      modifications is hampered by the dearth of effective high-throughput sequencing
      approaches for detecting, locating, and tracking their levels as a function of
      predetermined experimental factors. With the goal of confronting this knowledge
      gap, we devised a strategy for completing global surveys of all ribonucleotide
      modifications in a cell, which is based on the analysis of whole cell extracts by
      direct infusion electrospray ionization mass spectrometry (ESI-MS). Our approach
      eschews chromatographic separation to promote instead the direct application of
      MS techniques capable of providing detection, differentiation, and quantification
      of post-transcriptional modifications (PTMs) in complex ribonucleotide mixtures.
      Accurate mass analysis was used to carry out database-aided identification of
      PTMs, whereas multistep tandem mass spectrometry (MS(n)) and consecutive reaction
      monitoring (CRM) provided the necessary structural corroboration. We demonstrated
      that heat-map plots afforded by ion mobility spectrometry mass spectrometry (IMS
      MS) can provide comprehensive modification profiles that are unique for different
      cell types and metabolic states. We showed that isolated tRNA samples can be used
      as controlled sources of PTMs in standard-additions quantification. Intrinsic
      internal standards enable direct comparisons of heat-maps obtained under
      different experimental conditions, thus offering the opportunity to evaluate the
      global effects of such conditions on the expression levels of all PTMs
      simultaneously. This type of comparative analysis will be expected to support the
      investigation of the system biology of RNA modifications, which will be aimed at
      exploring mutual correlations of their expression levels and providing new
      valuable insights into their biological significance. 

PMID- 25995447
TI  - Chlamydia trachomatis Relies on Autonomous Phospholipid Synthesis for Membrane
      Biogenesis.
AB  - The obligate intracellular parasite Chlamydia trachomatis has a reduced genome
      and is thought to rely on its mammalian host cell for nutrients. Although several
      lines of evidence suggest C. trachomatis utilizes host phospholipids, the
      bacterium encodes all the genes necessary for fatty acid and phospholipid
      synthesis found in free living Gram-negative bacteria. Bacterially derived
      phospholipids significantly increased in infected HeLa cell cultures. These new
      phospholipids had a distinct molecular species composition consisting of
      saturated and branched-chain fatty acids. Biochemical analysis established the
      role of C. trachomatis-encoded acyltransferases in producing the new disaturated
      molecular species. There was no evidence for the remodeling of host phospholipids
      and no change in the size or molecular species composition of the
      phosphatidylcholine pool in infected HeLa cells. Host sphingomyelin was
      associated with C. trachomatis isolated by detergent extraction, but it may
      represent contamination with detergent-insoluble host lipids rather than being an
      integral bacterial membrane component. C. trachomatis assembles its membrane
      systems from the unique phospholipid molecular species produced by its own fatty
      acid and phospholipid biosynthetic machinery utilizing glucose, isoleucine, and
      serine. 

PMID- 25995448
TI  - A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type
      Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2.
AB  - Blood dendritic cell antigen 2 (BDCA-2; also designated CLEC4C or CD303) is
      uniquely expressed on plasmacytoid dendritic cells. Stimulation of BDCA-2 with
      antibodies leads to an anti-inflammatory response in these cells, but the natural
      ligands for the receptor are not known. The C-type carbohydrate recognition
      domain in the extracellular portion of BDCA-2 contains a signature motif typical
      of C-type animal lectins that bind mannose, glucose, or GlcNAc, yet it has been
      reported that BDCA-2 binds selectively to galactose-terminated, biantennary N
      linked glycans. A combination of glycan array analysis and binding competition
      studies with monosaccharides and natural and synthetic oligosaccharides have been
      used to define the binding epitope for BDCA-2 as the trisaccharide Galbeta1
      3/4GlcNAcbeta1-2Man. X-ray crystallography and mutagenesis studies show that
      mannose is ligated to the conserved Ca(2+) in the primary binding site that is
      characteristic of C-type carbohydrate recognition domains, and the GlcNAc and
      galactose residues make additional interactions in a wide, shallow groove
      adjacent to the primary binding site. As predicted from these studies, BDCA-2
      binds to IgG, which bears galactose-terminated glycans that are not commonly
      found attached to other serum glycoproteins. Thus, BDCA-2 has the potential to
      serve as a previously unrecognized immunoglobulin Fc receptor. 

PMID- 25995449
TI  - Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA
      Glycosylase.
AB  - The highly mutagenic A:oxoG (8-oxoguanine) base pair in DNA most frequently
      arises by aberrant replication of the primary oxidative lesion C:oxoG. This
      lesion is particularly insidious because neither of its constituent nucleobases
      faithfully transmit genetic information from the original C:G base pair. Repair
      of A:oxoG is initiated by adenine DNA glycosylase, which catalyzes hydrolytic
      cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY
      in bacteria and MUTYH in humans, scrupulously avoid processing of C:oxoG because
      cleavage of the C residue in C:oxoG would actually promote mutagenic conversion
      to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY,
      using a synthetic crystallography approach to capture the enzyme in the process
      of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only
      fleetingly. We find that MutY uses two distinct strategies to avoid presentation
      of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves
      as a decoy for C, and secondly, repulsive forces with a key active site residue
      prevent stable insertion of C into the nucleobase recognition pocket within the
      enzyme active site. 

PMID- 25995450
TI  - Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates
      DeltaNp63 Transcription through TEA Domain (TEAD) Transcription Factor.
AB  - Transcriptional co-activator with a PDZ binding domain (TAZ) is a WW domain
      containing transcriptional co-activator and a core component of an emerging Hippo
      signaling pathway that regulates organ size, tumorigenesis, metastasis, and drug
      resistance. TAZ regulates these biological functions by up-regulating downstream
      cellular genes through transactivation of transcription factors such as TEAD and
      TTF1. To understand the molecular mechanisms underlying TAZ-induced
      tumorigenesis, we have recently performed a gene expression profile analysis by
      overexpressing TAZ in mammary cells. In addition to the TAZ-up-regulated genes
      that were confirmed in our previous studies, we identified a large number of
      cellular genes that were down-regulated by TAZ. In this study, we have confirmed
      these down-regulated genes (including cytokines, chemokines, and p53 gene family
      members) as bona fide downstream transcriptional targets of TAZ. By using human
      breast and lung epithelial cells, we have further characterized DeltaNp63, a p53
      gene family member, and shown that TAZ suppresses DeltaNp63 mRNA, protein
      expression, and promoter activity through interaction with the transcription
      factor TEAD. We also show that TEAD can inhibit DeltaNp63 promoter activity and
      that TAZ can directly interact with DeltaNp63 promoter-containing TEAD binding
      sites. Finally, we provide functional evidence that down-regulation of DeltaNp63
      by TAZ may play a role in regulating cell migration. Altogether, this study
      provides novel evidence that the Hippo component TAZ can function as a co
      repressor and regulate biological functions by negatively regulating downstream
      cellular genes. 

PMID- 25995451
TI  - Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi
      Signaling.
AB  - Apela (APJ early endogenous ligand, also known as elabela or toddler) is a
      recently discovered peptide hormone. Based on genetic studies in zebrafish, apela
      was found to be important for endoderm differentiation and heart development
      during embryogenesis. Although common phenotypes of apela and APJ-null zebrafish
      during embryonic development suggested that apela interacts with the APJ
      receptor, kinetics of apela binding to APJ and intracellular signaling pathways
      for apela remain unknown. The role of apela in adults is also uncertain. Using a
      chimeric apela ligand, we showed direct binding of apela to APJ with high
      affinity (Kd = 0.51 nm) and the ability of apelin, the known peptide ligand for
      APJ, to compete for apela binding. Apela, similar to apelin, acts through the
      inhibitory G protein pathway by inhibiting forskolin-stimulated cAMP production
      and by inducing ERK1/2 phosphorylation. In adult rats, apela is expressed
      exclusively in the kidney, unlike the wide tissue distribution of apelin. In vivo
      studies demonstrated the ability of apela to regulate fluid homeostasis by
      increasing diuresis and water intake. Dose-response studies further indicated
      that apela induces 2- and 5-fold higher maximal responses than apelin in ERK1/2
      phosphorylation and diuresis/water intake, respectively. After designing an apela
      antagonist, we further demonstrated the role of endogenous ligand(s) in
      regulating APJ-mediated fluid homeostasis. Our results identified apela as a
      potent peptide hormone capable of regulating fluid homeostasis in adult kidney
      through coupling to the APJ-mediated Gi signaling pathway. 

PMID- 25995452
TI  - Structural Mechanisms of Mutant Huntingtin Aggregation Suppression by the
      Synthetic Chaperonin-like CCT5 Complex Explained by Cryoelectron Tomography.
AB  - Huntington disease, a neurodegenerative disorder characterized by functional
      deficits and loss of striatal neurons, is linked to an expanded and unstable CAG
      trinucleotide repeat in the huntingtin gene (HTT). This DNA sequence translates
      to a polyglutamine repeat in the protein product, leading to mutant huntingtin
      (mHTT) protein aggregation. The aggregation of mHTT is inhibited in vitro and in
      vivo by the TCP-1 ring complex (TRiC) chaperonin. Recently, a novel complex
      comprised of a single type of TRiC subunit has been reported to inhibit mHTT
      aggregation. Specifically, the purified CCT5 homo-oligomer complex, when compared
      with TRiC, has a similar structure, ATP use, and substrate refolding activity,
      and, importantly, it also inhibits mHTT aggregation. Using an aggregation
      suppression assay and cryoelectron tomography coupled with a novel computational
      classification method, we uncover the interactions between the synthetic CCT5
      complex (~ 1 MDa) and aggregates of mutant huntingtin exon 1 containing 46
      glutamines (mHTTQ46-Ex1). We find that, in a similar fashion to TRiC, synthetic
      CCT5 complex caps mHTT fibrils at their tips and encapsulates mHTT oligomers,
      providing a structural description of the inhibition of mHTTQ46-Ex1 by CCT5
      complex and a shared mechanism of mHTT inhibition between TRiC chaperonin and the
      CCT5 complex: cap and contain.

PMID- 25995453
TI  - SET7/9 Enzyme Regulates Cytokine-induced Expression of Inducible Nitric-oxide
      Synthase through Methylation of Lysine 4 at Histone 3 in the Islet beta Cell.
AB  - SET7/9 is an enzyme that methylates histone 3 at lysine 4 (H3K4) to maintain
      euchromatin architecture. Although SET7/9 is enriched in islets and contributes
      to the transactivation of beta cell-specific genes, including Ins1 and Slc2a,
      SET7/9 has also been reported to bind the p65 subunit of nuclear factor kappaB in
      non-beta cells and modify its transcriptional activity. Given that inflammation
      is a central component of beta cell dysfunction in Type 1 and Type 2 diabetes,
      the aim of this study was to elucidate the role of SET7/9 in proinflammatory
      cytokine signaling in beta cells. To induce inflammation, betaTC3 insulinoma
      cells were treated with IL-1beta, TNF-alpha, and IFN-gamma. Cytokine treatment
      led to increased expression of inducible nitric-oxide synthase, which was
      attenuated by the diminution of SET7/9 using RNA interference. Consistent with
      previous reports, SET7/9 was co-immunoprecipitated with p65 and underwent
      cytosolic to nuclear translocation in response to cytokines. ChIP analysis
      demonstrated augmented H3K4 mono- and dimethylation of the proximal Nos2 promoter
      with cytokine exposure. SET7/9 was found to occupy this same region, whereas
      SET7/9 knockdown attenuated cytokine-induced histone methylation of the Nos2
      gene. To test this relationship further, islets were isolated from SET7/9
      deficient and wild-type mice and treated with IL-1beta, TNF-alpha, and IFN-gamma.
      Cytokine-induced Nos2 expression was reduced in the islets from SET7/9 knock-out
      mice. Together, our findings suggest that SET7/9 contributes to Nos2
      transcription and proinflammatory cytokine signaling in the pancreatic beta cell
      through activating histone modifications. 

PMID- 25995454
TI  - Casein Kinase 2 (CK2)-mediated Phosphorylation of Hsp90beta as a Novel Mechanism
      of Rifampin-induced MDR1 Expression.
AB  - The P-glycoprotein (P-gp) encoded by the MDR1 gene is a drug-exporting
      transporter located in the cellular membrane. P-gp induction is regarded as one
      of the main mechanisms underlying drug-induced resistance. Although there is
      great interest in the regulation of P-gp expression, little is known about its
      underlying regulatory mechanisms. In this study, we demonstrate that casein
      kinase 2 (CK2)-mediated phosphorylation of heat shock protein 90beta (Hsp90beta)
      and subsequent stabilization of PXR is a key mechanism in the regulation of MDR1
      expression. Furthermore, we show that CK2 is directly activated by rifampin. Upon
      exposure to rifampin, CK2 catalyzes the phosphorylation of Hsp90beta at the Ser
      225/254 residues. Phosphorylated Hsp90beta then interacts with PXR, causing a
      subsequent increase in its stability, leading to the induction of P-gp
      expression. In addition, inhibition of CK2 and Hsp90beta enhances the down
      regulation of PXR and P-gp expression. The results of this study may facilitate
      the development of new strategies to prevent multidrug resistance and provide a
      plausible mechanism for acquired drug resistance by CK2-mediated regulation of P
      gp expression. 

PMID- 25995456
TI  - Parsing and predicting increased noise in visual cortex.

PMID- 25995455
TI  - Identification of a Compound That Disrupts Binding of Amyloid-beta to the Prion
      Protein Using a Novel Fluorescence-based Assay.
AB  - The prion protein (PrP) has been implicated both in prion diseases such as
      Creutzfeldt-Jakob disease, where its monomeric cellular isoform (PrP(C)) is
      recruited into pathogenic self-propagating polymers of misfolded protein, and in
      Alzheimer disease, where PrP(C) may act as a receptor for synaptotoxic oligomeric
      forms of amyloid-beta (Abeta). There has been considerable interest in
      identification of compounds that bind to PrP(C), stabilizing its native fold and
      thereby acting as pharmacological chaperones to block prion propagation and
      pathogenesis. However, compounds binding PrP(C) could also inhibit the binding of
      toxic Abeta species and may have a role in treating Alzheimer disease, a highly
      prevalent dementia for which there are currently no disease-modifying treatments.
      However, the absence of a unitary, readily measurable, physiological function of
      PrP makes screening for ligands challenging, and the highly heterogeneous nature
      of Abeta oligomer preparations makes conventional competition binding assays
      difficult to interpret. We have therefore developed a high-throughput screen that
      utilizes site-specifically fluorescently labeled protein to identify compounds
      that bind to PrP and inhibit both Abeta binding and prion propagation. Following
      a screen of 1,200 approved drugs, we identified Chicago Sky Blue 6B as the first
      small molecule PrP ligand capable of inhibiting Abeta binding, demonstrating the
      feasibility of development of drugs to block this interaction. The interaction of
      Chicago Sky Blue 6B was characterized by isothermal titration calorimetry, and
      its ability to inhibit Abeta binding and reduce prion levels was established in
      cell-based assays. 

PMID- 25995457
TI  - Dynamic network mechanisms of relational integration.
AB  - A prominent hypothesis states that specialized neural modules within the human
      lateral frontopolar cortices (LFPCs) support "relational integration" (RI), the
      solving of complex problems using inter-related rules. However, it has been
      proposed that LFPC activity during RI could reflect the recruitment of additional
      "domain-general" resources when processing more difficult problems in general as
      opposed to RI specifically. Moreover, theoretical research with computational
      models has demonstrated that RI may be supported by dynamic processes that occur
      throughout distributed networks of brain regions as opposed to within a discrete
      computational module. Here, we present fMRI findings from a novel deductive
      reasoning paradigm that controls for general difficulty while manipulating RI
      demands. In accordance with the domain-general perspective, we observe an
      increase in frontoparietal activation during challenging problems in general as
      opposed to RI specifically. Nonetheless, when examining frontoparietal activity
      using analyses of phase synchrony and psychophysiological interactions, we
      observe increased network connectivity during RI alone. Moreover, dynamic causal
      modeling with Bayesian model selection identifies the LFPC as the effective
      connectivity source. Based on these results, we propose that during RI an
      increase in network connectivity and a decrease in network metastability allows
      rules that are coded throughout working memory systems to be dynamically bound.
      This change in connectivity state is top-down propagated via a hierarchical
      system of domain-general networks with the LFPC at the apex. In this manner, the
      functional network perspective reconciles key propositions of the globalist,
      modular, and computational accounts of RI within a single unified framework. 

PMID- 25995459
TI  - Input and output gain modulation by the lateral interhemispheric network in early
      visual cortex.
AB  - Neurons in the cerebral cortex are constantly integrating different types of
      inputs. Dependent on their origin, these inputs can be modulatory in many ways
      and, for example, change the neuron's responsiveness, sensitivity, or
      selectivity. To investigate the modulatory role of lateral input from the same
      level of cortical hierarchy, we recorded in the primary visual cortex of cats
      while controlling synaptic input from the corresponding contralateral hemisphere
      by reversible deactivation. Most neurons showed a pronounced decrease in their
      response to a visual stimulus of different contrasts and orientations. This
      indicates that the lateral network acts via an unspecific gain-setting mechanism,
      scaling the output of a neuron. However, the interhemispheric input also changed
      the contrast sensitivity of many neurons, thereby acting on the input. Such a
      contrast gain mechanism has important implications because it extends the role of
      the lateral network from pure response amplification to the modulation of a
      specific feature. Interestingly, for many neurons, we found a mixture of input
      and output gain modulation. Based on these findings and the known physiology of
      callosal connections in the visual system, we developed a simple model of lateral
      interhemispheric interactions. We conclude that the lateral network can act
      directly on its target, leading to a sensitivity change of a specific feature,
      while at the same time it also can act indirectly, leading to an unspecific gain
      setting. The relative contribution of these direct and indirect network effects
      determines the outcome for a particular neuron. 

PMID- 25995458
TI  - Novel SCN9A mutations underlying extreme pain phenotypes: unexpected
      electrophysiological and clinical phenotype correlations.
AB  - The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is
      exemplified by the heterogeneity of clinical phenotypes associated with its
      mutation. Gain-of-function mutations are typically pain-causing and have been
      associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain
      disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation,
      whereas mutations that alter steady-state fast inactivation often lead to PEPD.
      In contrast, nonfunctional mutations in SCN9A are known to underlie congenital
      insensitivity to pain (CIP). Although well documented, the correlation between
      SCN9A genotypes and clinical phenotypes is still unclear. Here we report three
      families with novel SCN9A mutations. In a multiaffected dominant family with IEM,
      we found the heterozygous change L245 V. Electrophysiological characterization
      showed that this mutation did not affect channel activation but instead resulted
      in incomplete fast inactivation and a small hyperpolarizing shift in steady-state
      slow inactivation, characteristics more commonly associated with PEPD. In two
      compound heterozygous CIP patients, we found mutations that still retained
      functionality of the channels, with two C-terminal mutations (W1775R and L1831X)
      exhibiting a depolarizing shift in channel activation. Two mutations (A1236E and
      L1831X) resulted in a hyperpolarizing shift in steady-state fast inactivation. To
      our knowledge, these are the first descriptions of mutations with some retained
      channel function causing CIP. This study emphasizes the complex genotype
      phenotype correlations that exist for SCN9A and highlights the C-terminal
      cytoplasmic region of NaV1.7 as a critical region for channel function,
      potentially facilitating analgesic drug development studies. 

PMID- 25995460
TI  - Covert shifts of spatial attention in the macaque monkey.
AB  - In the awake state, shifts of spatial attention alternate with periods of
      sustained attention at a fixed location or object. Human fMRI experiments
      revealed the critical role of the superior parietal lobule (SPL) in shifting
      spatial attention, a finding not predicted by human lesion studies and monkey
      electrophysiology. To investigate whether a potential homolog of the human SPL
      shifting region exists in monkeys (Macaca mulatta), we adopted an event-related
      fMRI paradigm that closely resembled a human experiment (Molenberghs et al.,
      2007). In this paradigm, a pair of relevant and irrelevant shapes was
      continuously present on the horizontal meridian. Subjects had to covertly detect
      a dimming of the relevant shape while ignoring the irrelevant dimmings. The
      events of interest consisted of the replacement of one stimulus pair by the next.
      During shift but not stay events, the relevant shape of the new pair appeared at
      the contralateral position relative to the previous one. Spatial shifting events
      activated parietal areas V6/V6A and medial intraparietal area, caudo-dorsal
      visual areas, the most posterior portion of the superior temporal sulcus, and
      several smaller frontal areas. These areas were not activated during passive
      stimulation with the same sensory stimuli. During stay events, strong direction
      sensitive attention signals were observed in a distributed set of contralateral
      visual, temporal, parietal, and lateral prefrontal areas, the vast majority
      overlapping with the sensory stimulus representation. We suggest medial
      intraparietal area and V6/V6A as functional counterparts of human SPL because
      they contained the most widespread shift signals in the absence of contralateral
      stay activity, resembling the functional characteristics of the human SPL
      shifting area. 

PMID- 25995462
TI  - Decoding actions at different levels of abstraction.
AB  - Brain regions that mediate action understanding must contain representations that
      are action specific and at the same time tolerate a wide range of perceptual
      variance. Whereas progress has been made in understanding such generalization
      mechanisms in the object domain, the neural mechanisms to conceptualize actions
      remain unknown. In particular, there is ongoing dissent between motor-centric and
      cognitive accounts whether premotor cortex or brain regions in closer relation to
      perceptual systems, i.e., lateral occipitotemporal cortex, contain neural
      populations with such mapping properties. To date, it is unclear to which degree
      action-specific representations in these brain regions generalize from concrete
      action instantiations to abstract action concepts. However, such information
      would be crucial to differentiate between motor and cognitive theories. Using ROI
      based and searchlight-based fMRI multivoxel pattern decoding, we sought brain
      regions in human cortex that manage the balancing act between specificity and
      generality. We investigated a concrete level that distinguishes actions based on
      perceptual features (e.g., opening vs closing a specific bottle), an intermediate
      level that generalizes across movement kinematics and specific objects involved
      in the action (e.g., opening different bottles with cork or screw cap), and an
      abstract level that additionally generalizes across object category (e.g.,
      opening bottles or boxes). We demonstrate that the inferior parietal and
      occipitotemporal cortex code actions at abstract levels whereas the premotor
      cortex codes actions at the concrete level only. Hence, occipitotemporal, but not
      premotor, regions fulfill the necessary criteria for action understanding. This
      result is compatible with cognitive theories but strongly undermines motor
      theories of action understanding. 

PMID- 25995461
TI  - The contribution of raised intraneuronal chloride to epileptic network activity.
AB  - Altered inhibitory function is an important facet of epileptic pathology. A key
      concept is that GABAergic activity can become excitatory if intraneuronal
      chloride rises. However, it has proved difficult to separate the role of raised
      chloride from other contributory factors in complex network phenomena, such as
      epileptic pathology. Therefore, we asked what patterns of activity are associated
      with chloride dysregulation by making novel use of Halorhodopsin to load clusters
      of mouse pyramidal cells artificially with Cl(-). Brief (1-10 s) activation of
      Halorhodopsin caused substantial positive shifts in the GABAergic reversal
      potential that were proportional to the charge transfer during the illumination
      and in adult neocortical pyramidal neurons decayed with a time constant of tau =
      8.0 +/- 2.8s. At the network level, these positive shifts in EGABA produced a
      transient rise in network excitability, with many distinctive features of
      epileptic foci, including high-frequency oscillations with evidence of out-of
      phase firing (Ibarz et al., 2010). We show how such firing patterns can arise
      from quite small shifts in the mean intracellular Cl(-) level, within
      heterogeneous neuronal populations. Notably, however, chloride loading by itself
      did not trigger full ictal events, even with additional electrical stimulation to
      the underlying white matter. In contrast, when performed in combination with low,
      subepileptic levels of 4-aminopyridine, Halorhodopsin activation rapidly induced
      full ictal activity. These results suggest that chloride loading has at most an
      adjunctive role in ictogenesis. Our simulations also show how chloride loading
      can affect the jitter of action potential timing associated with imminent
      recruitment to an ictal event (Netoff and Schiff, 2002). 

PMID- 25995463
TI  - PKMzeta, but not PKClambda, is rapidly synthesized and degraded at the neuronal
      synapse.
AB  - Synthesizing, localizing, and stabilizing new protein copies at synapses are
      crucial factors in maintaining the synaptic changes required for storing long
      term memories. PKMzeta recently emerged as a molecule putatively responsible for
      maintaining encoded memories over time because its presence correlates with late
      LTP and because its inhibition disrupts LTP in vitro and long-term memory storage
      in vivo. Here we investigated PKMzeta stability in rat neurons to better
      understand its role during information encoding and storage. We used TimeSTAMP
      reporters to track the synthesis and degradation of PKMzeta as well as a related
      atypical PKC, PKClambda. These reporters revealed that both PKMzeta and PKClambda
      were upregulated after chemical LTP induction; however, these new PKMzeta copies
      exhibited more rapid turnover than basally produced PKMzeta, particularly in
      dendritic spines. In contrast to PKMzeta, new PKClambda copies exhibited elevated
      stability. Stable information storage over long periods of time is more
      challenging the shorter the metabolic lifetime of the candidate molecules. 

PMID- 25995464
TI  - Rhythmic auditory cortex activity at multiple timescales shapes stimulus-response
      gain and background firing.
AB  - The phase of low-frequency network activity in the auditory cortex captures
      changes in neural excitability, entrains to the temporal structure of natural
      sounds, and correlates with the perceptual performance in acoustic tasks.
      Although these observations suggest a causal link between network rhythms and
      perception, it remains unknown how precisely they affect the processes by which
      neural populations encode sounds. We addressed this question by analyzing neural
      responses in the auditory cortex of anesthetized rats using stimulus-response
      models. These models included a parametric dependence on the phase of local field
      potential rhythms in both stimulus-unrelated background activity and the stimulus
      response transfer function. We found that phase-dependent models better
      reproduced the observed responses than static models, during both stimulation
      with a series of natural sounds and epochs of silence. This was attributable to
      two factors: (1) phase-dependent variations in background firing (most prominent
      for delta; 1-4 Hz); and (2) modulations of response gain that rhythmically
      amplify and attenuate the responses at specific phases of the rhythm (prominent
      for frequencies between 2 and 12 Hz). These results provide a quantitative
      characterization of how slow auditory cortical rhythms shape sound encoding and
      suggest a differential contribution of network activity at different timescales.
      In addition, they highlight a putative mechanism that may implement the selective
      amplification of appropriately timed sound tokens relative to the phase of
      rhythmic auditory cortex activity. 

PMID- 25995465
TI  - Activity of somatosensory-responsive neurons in high subdivisions of SI cortex
      during locomotion.
AB  - Responses of neurons in the primary somatosensory cortex during movements are
      poorly understood, even during such simple tasks as walking on a flat surface. In
      this study, we analyzed spike discharges of neurons in the rostral bank of the
      ansate sulcus (areas 1-2) in 2 cats while the cats walked on a flat surface or on
      a horizontal ladder, a complex task requiring accurate stepping. All neurons (n =
      82) that had receptive fields (RFs) on the contralateral forelimb exhibited
      frequency modulation of their activity that was phase locked to the stride cycle
      during simple locomotion. Neurons with proximal RFs (upper arm/shoulder) and
      pyramidal tract-projecting neurons (PTNs) with fast-conducting axons tended to
      fire at peak rates in the middle of the swing phase, whereas neurons with RFs on
      the distal limb (wrist/paw) and slow-conducting PTNs typically showed peak firing
      at the transition between swing and stance phases. Eleven of 12 neurons with
      tactile RFs on the volar forepaw began firing toward the end of swing, with peak
      activity occurring at the moment of foot contact with floor, thereby preceding
      the evoked sensory volley from touch receptors. Requirement to step accurately on
      the ladder affected 91% of the neurons, suggesting their involvement in control
      of accuracy of stepping. During both tasks, neurons exhibited a wide variety of
      spike distributions within the stride cycle, suggesting that, during either
      simple or ladder locomotion, they represent the cycling somatosensory events in
      their activity both predictively before and reflectively after these events take
      place. 

PMID- 25995466
TI  - Blocking stroke-induced immunodeficiency increases CNS antigen-specific
      autoreactivity but does not worsen functional outcome after experimental stroke.
AB  - Stroke-induced immunodepression (SIDS) is an essential cause of poststroke
      infections. Pharmacological inhibition of SIDS appears promising in preventing
      life-threatening infections in stroke patients. However, SIDS might represent an
      adaptive mechanism preventing autoreactive immune responses after stroke. To
      address this, we used myelin oligodendrocyte glycoprotein (MOG) T-cell receptor
      transgenic (2D2) mice where >80% of peripheral CD4(+) T cells express a
      functional receptor for MOG. We investigated in a murine model of middle cerebral
      artery occlusion the effect of blocking SIDS by inhibiting body's main stress
      axes, the sympathetic nervous system (SNS) with propranolol and the hypothalamic
      pituitary-adrenal axis (HPA) with mifepristone. Blockade of both stress axes
      robustly reduced infarct volumes, decreased infection rate, and increased long
      term survival of 2D2 and C57BL/6J wild-type mice. Despite these protective
      effects, blockade of SIDS increased CNS antigen-specific Type1 T helper cell
      (Th1) responses in the brains of 2D2 mice 14 d after middle cerebral artery
      occlusion. One month after experimental stroke, 2D2 mice developed signs of
      polyradiculitis, which were diminished by SIDS blockade. Adoptive transfer of
      CD4(+) T cells, isolated from 2D2 mice, into lymphocyte-deficient Rag-1KO mice
      did not reveal differences between SIDS blockade and vehicle treatment in
      functional long-term outcome after stroke. In conclusion, inhibiting SIDS by
      pharmacological blockade of body's stress axes increases autoreactive CNS antigen
      specific T-cell responses in the brain but does not worsen functional long-term
      outcome after experimental stroke, even in a mouse model where CNS antigen
      specific autoreactive T-cell responses are boosted. 

PMID- 25995467
TI  - Cortical thinning explains changes in sleep slow waves during adulthood.
AB  - Sleep slow waves (SWs) change considerably throughout normal aging. In humans,
      SWs are generated and propagate on a structural backbone of highly interconnected
      cortical regions that form most of the default mode network, such as the insula,
      cingulate cortices, temporal lobe, parietal lobe, and medial frontal lobe.
      Regions in this network undergo cortical thinning and breakdown in structural and
      functional connectivity over the course of normal aging. In this study, we
      investigated how changes in cortical thickness (CT), a measure of gray matter
      integrity, are involved in modifications of sleep SWs during adulthood in humans.
      Thirty young (mean age = 23.49 years; SD = 2.79) and 33 older (mean age = 60.35
      years; SD = 5.71) healthy subjects underwent a nocturnal polysomnography and T1
      MRI. We show that, when controlling for age, higher SW density (nb/min of
      nonrapid eye movement sleep) was associated with higher CT in cortical regions
      involved in SW generation surrounding the lateral fissure (insula, superior
      temporal, parietal, middle frontal), whereas higher SW amplitude was associated
      with higher CT in middle frontal, medial prefrontal, and medial posterior
      regions. Mediation analyses demonstrated that thinning in a network of cortical
      regions involved in SW generation and propagation, but also in cognitive
      functions, explained the age-related decrease in SW density and amplitude.
      Altogether, our results suggest that microstructural degradation of specific
      cortical regions compromise SW generation and propagation in older subjects,
      critically contributing to age-related changes in SW oscillations. 

PMID- 25995468
TI  - Enhanced procedural learning of speech sound categories in a genetic variant of
      FOXP2.
AB  - A mutation of the forkhead box protein P2 (FOXP2) gene is associated with severe
      deficits in human speech and language acquisition. In rodents, the humanized form
      of FOXP2 promotes faster switching from declarative to procedural learning
      strategies when the two learning systems compete. Here, we examined a
      polymorphism of FOXP2 (rs6980093) in humans (214 adults; 111 females) for
      associations with non-native speech category learning success. Neurocomputational
      modeling results showed that individuals with the GG genotype shifted faster to
      procedural learning strategies, which are optimal for the task. These findings
      support an adaptive role for the FOXP2 gene in modulating the function of neural
      learning systems that have a direct bearing on human speech category learning. 

PMID- 25995469
TI  - Relating cerebellar purkinje cell activity to the timing and amplitude of
      conditioned eyelid responses.
AB  - How Purkinje cell (PC) activity may be altered by learning is central to theories
      of the cerebellum. Pavlovian eyelid conditioning, because of how directly it
      engages the cerebellum, has helped reveal many aspects of cerebellar learning and
      the underlying mechanisms. Theories of cerebellar learning assert that climbing
      fiber inputs control plasticity at synapses onto PCs, and thus PCs control the
      expression of learned responses. We tested this assertion by recording 184 eyelid
      PCs and 240 non-eyelid PCs during the expression of conditioned eyelid responses
      (CRs) in well trained rabbits. By contrasting the responses of eyelid and non
      eyelid PCs and by contrasting the responses of eyelid PCs under conditions that
      produce differently timed CRs, we test the hypothesis that learning-related
      changes in eyelid PCs contribute to the learning and adaptive timing of the CRs.
      We used a variety of analyses to test the quantitative relationships between
      eyelid PC responses and the kinematic properties of the eyelid CRs. We find that
      the timing of eyelid PC responses varies systematically with the timing of the
      behavioral CRs and that there are differences in the magnitude of eyelid PC
      responses between larger-CR, smaller-CR, and non-CR trials. However, eyelid PC
      activity does not encode any single kinematic property of the behavioral CRs at a
      fixed time lag, nor does it linearly encode CR amplitude. Even so, the results
      are consistent with the hypothesis that learning-dependent changes in PC activity
      contribute to the adaptively timed expression of conditioned eyelid responses. 

PMID- 25995470
TI  - Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the
      olfactory bulb and improves olfactory function.
AB  - Recent discoveries have suggested that adult neurogenesis in the subventricular
      zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of
      olfactory behavior in mice. However, it is unclear whether conditional and
      selective enhancement of adult neurogenesis by genetic approaches is sufficient
      to improve olfactory function under physiological conditions or after injury.
      Furthermore, specific signaling mechanisms regulating adult neurogenesis in the
      SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase
      selectively expressed in the neurogenic regions of the adult brain, plays a
      critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in
      mouse model, we report here that inducible and targeted activation of the
      endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis
      in the OB by increasing cell survival and neuronal differentiation. This
      conditional ERK5 activation also improves short-term olfactory memory and odor
      cued associative olfactory learning under normal physiological conditions.
      Furthermore, these mice show enhanced recovery of olfactory function and have
      more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory
      epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling
      pathway regulating adult neurogenesis in the SVZ/OB, and that conditional
      activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the
      OB thereby improving olfactory function both under normal conditions and after
      injury. 

PMID- 25995472
TI  - Noradrenaline and dopamine neurons in the reward/effort trade-off: a direct
      electrophysiological comparison in behaving monkeys.
AB  - Motivation determines multiple aspects of behavior, including action selection
      and energization of behavior. Several components of the underlying neural systems
      have been examined closely, but the specific role of the different
      neuromodulatory systems in motivation remains unclear. Here, we compare directly
      the activity of dopaminergic neurons from the substantia nigra pars compacta and
      noradrenergic neurons from the locus coeruleus in monkeys performing a task
      manipulating the reward/effort trade-off. Consistent with previous reports,
      dopaminergic neurons encoded the expected reward, but we found that they also
      anticipated the upcoming effort cost in connection with its negative influence on
      action selection. Conversely, the firing of noradrenergic neurons increased with
      both pupil dilation and effort production in relation to the energization of
      behavior. Therefore, this work underlines the contribution of dopamine to effort
      based decision making and uncovers a specific role of noradrenaline in energizing
      behavior to face challenges. 

PMID- 25995471
TI  - Translational control of myelin basic protein expression by ERK2 MAP kinase
      regulates timely remyelination in the adult brain.
AB  - Successful myelin repair in the adult CNS requires the robust and timely
      production of myelin proteins to generate new myelin sheaths. The underlying
      regulatory mechanisms and complex molecular basis of myelin regeneration,
      however, remain poorly understood. Here, we investigate the role of ERK MAP
      kinase signaling in this process. Conditional deletion of Erk2 from cells of the
      oligodendrocyte lineage resulted in delayed remyelination following demyelinating
      injury to the adult mouse corpus callosum. The delayed repair occurred as a
      result of a specific deficit in the translation of the major myelin protein, MBP.
      In the absence of ERK2, activation of the ribosomal protein S6 kinase (p70S6K)
      and its downstream target, ribosomal protein S6 (S6RP), was impaired at a
      critical time when premyelinating oligodendrocytes were transitioning to mature
      cells capable of generating new myelin sheaths. Thus, we have described an
      important link between the ERK MAP kinase signaling cascade and the translational
      machinery specifically in remyelinating oligodendrocytes in vivo. These results
      suggest an important role for ERK2 in the translational control of MBP, a myelin
      protein that appears critical for ensuring the timely generation of new myelin
      sheaths following demyelinating injury in the adult CNS. 

PMID- 25995473
TI  - Selective deletion of cochlear hair cells causes rapid age-dependent changes in
      spiral ganglion and cochlear nucleus neurons.
AB  - During nervous system development, critical periods are usually defined as early
      periods during which manipulations dramatically change neuronal structure or
      function, whereas the same manipulations in mature animals have little or no
      effect on the same property. Neurons in the ventral cochlear nucleus (CN) are
      dependent on excitatory afferent input for survival during a critical period of
      development. Cochlear removal in young mammals and birds results in rapid death
      of target neurons in the CN. Cochlear removal in older animals results in little
      or no neuron death. However, the extent to which hair-cell-specific afferent
      activity prevents neuronal death in the neonatal brain is unknown. We further
      explore this phenomenon using a new mouse model that allows temporal control of
      cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT)
      receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete
      loss of organ of Corti hair cells within 1 week of injection regardless of the
      age of injection. Injection of DT did not influence surrounding supporting cells
      directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of
      hair cells in neonates resulted in rapid and profound neuronal loss in the
      ventral CN, but not when hair cells were eliminated at a more mature age. In
      addition, normal survival of SGNs was dependent on hair cell integrity early in
      development and less so in mature animals. This defines a previously undocumented
      critical period for SGN survival. 

PMID- 25995474
TI  - Integrating temperature with odor processing in the olfactory bulb.
AB  - Temperature perception has long been classified as a somesthetic function solely.
      However, in recent years several studies brought evidence that temperature
      perception also takes place in the olfactory system of rodents. Temperature has
      been described as an effective stimulus for sensory neurons of the Grueneberg
      ganglion located at the entrance of the nose. Here, we investigate whether a
      neuronal trace of temperature stimulation can be observed in the glomeruli and
      mitral cells of the olfactory bulb, using calcium imaging and fast line-scanning
      microscopy. We show in the Xenopus tadpole system that the gamma-glomerulus,
      which receives input from olfactory neurons, is highly sensitive to temperature
      drops at the olfactory epithelium. We observed that thermo-induced activity in
      the gamma-glomerulus is conveyed to the mitral cells innervating this specific
      neuropil. Surprisingly, a substantial number of thermosensitive mitral cells were
      also chemosensitive. Moreover, we report another unique feature of the gamma
      glomerulus: it receives ipsilateral and contralateral afferents. The latter
      fibers pass through the contralateral bulb, cross the anterior commissure, and
      then run to the ipsilateral olfactory bulb, where they target the gamma
      glomerulus. Temperature drops at the contralateral olfactory epithelium also
      induced responses in the gamma-glomerulus and in mitral cells. Temperature thus
      appears to be a relevant physiological input to the Xenopus olfactory system.
      Each olfactory bulb integrates and codes temperature signals originating from
      receptor neurons of the ipsilateral and contralateral nasal cavities. Finally,
      temperature and chemical information is processed in shared cellular networks. 

PMID- 25995475
TI  - A structural and genotypic scaffold underlying temporal integration.
AB  - The accumulation and storage of information over time, temporal integration, is
      key to numerous behaviors. Many oculomotor tasks depend on integration of eye
      velocity signals to eye-position commands, a transformation achieved by a
      hindbrain cell group termed the velocity-to-position neural integrator (VPNI).
      Although the VPNI's coding properties have been well characterized, its mechanism
      of function remains poorly understood because few links exist between neuronal
      activity, structure, and genotypic identity. To fill this gap, we used calcium
      imaging and single-cell electroporation during oculomotor behaviors to map VPNI
      neural activity in zebrafish onto a hindbrain scaffold consisting of alternating
      excitatory and inhibitory parasagittal stripes. Three distinct classes of VPNI
      cells were identified. One glutamatergic class was medially located along a
      stripe associated with the alx transcription factor; these cells had ipsilateral
      projections terminating near abducens motoneurons and collateralized extensively
      within the ipsilateral VPNI in a manner consistent with integration through
      recurrent excitation. A second glutamatergic class was more laterally located
      along a stripe associated with transcription factor dbx1b; these glutamatergic
      cells had contralateral projections collateralizing near abducens motoneurons,
      consistent with a role in disconjugate eye movements. A third class,
      immunohistochemically suggested to be GABAergic, was located primarily in the
      dbx1b stripe and also had contralateral projections terminating near abducens
      motoneurons; these cells collateralized extensively in the dendritic field of
      contralateral VPNI neurons, consistent with a role in coordinating activity
      between functionally opposing populations. This mapping between VPNI activity,
      structure, and genotype may provide a blueprint for understanding the mechanisms
      governing temporal integration. 

PMID- 25995476
TI  - A bidirectional link between brain oscillations and geometric patterns.
AB  - Like hallucinogenic drugs, full-field flickering visual stimulation produces
      regular, geometric hallucinations such as radial or spiral patterns.
      Computational and theoretical models have revealed that the geometry of these
      hallucinations can be related to functional neuro-anatomy. However, while
      experimental evidence links both visual flicker and hallucinogenic drugs to
      upward and downward modulations of brain oscillatory activity, the exact relation
      between brain oscillations and geometric hallucinations remains a mystery. Here
      we demonstrate that, in human observers, this link is bidirectional. The same
      flicker frequencies that preferentially induced radial (<10 Hz) or spiral (10-20
      Hz) hallucinations in a behavioral experiment involving full-field uniform
      flicker without any actual shape displayed, also showed selective oscillatory EEG
      enhancement when observers viewed a genuine static image of a radial or spiral
      pattern without any flicker. This bidirectional property constrains the possible
      neuronal events at the origin of visual hallucinations, and further suggests that
      brain oscillations, which are strictly temporal in nature, could nonetheless act
      as preferential channels for spatial information. 

PMID- 25995478
TI  - Connections between intraparietal sulcus and a sensorimotor network underpin
      sustained tactile attention.
AB  - Previous studies on sustained tactile attention draw conclusions about underlying
      cortical networks by averaging over experimental conditions without considering
      attentional variance in single trials. This may have formed an imprecise picture
      of brain processes underpinning sustained tactile attention. In the present
      study, we simultaneously recorded EEG-fMRI and used modulations of steady-state
      somatosensory evoked potentials (SSSEPs) as a measure of attentional trial-by
      trial variability. Therefore, frequency-tagged streams of vibrotactile
      stimulations were simultaneously presented to both index fingers. Human
      participants were cued to sustain attention to either the left or right finger
      stimulation and to press a button whenever they perceived a target pulse embedded
      in the to-be-attended stream. In-line with previous studies, a classical general
      linear model (GLM) analysis based on cued attention conditions revealed increased
      activity mainly in somatosensory and cerebellar regions. Yet, parametric modeling
      of the BOLD response using simultaneously recorded SSSEPs as a marker of
      attentional trial-by-trial variability quarried the intraparietal sulcus (IPS).
      The IPS in turn showed enhanced functional connectivity to a modality-unspecific
      attention network. However, this was only revealed on the basis of cued attention
      conditions in the classical GLM. By considering attentional variability as
      captured by SSSEPs, the IPS showed increased connectivity to a sensorimotor
      network, underpinning attentional selection processes between competing tactile
      stimuli and action choices (press a button or not). Thus, the current findings
      highlight the potential value by considering attentional variations in single
      trials and extend previous knowledge on the role of the IPS in tactile attention.

PMID- 25995477
TI  - Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.
AB  - An imbalance in molecular signaling cascades and transcriptional regulation in
      nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in
      dopamine D1 versus D2 receptors, is implicated in the behavioral responses to
      psychostimulants. To provide further insight into the molecular mechanisms
      occurring in MSN subtypes by cocaine, we examined the transcription factor early
      growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical
      cocaine-mediated signaling pathways and because Egr3-binding sites are found on
      promoters of key cocaine-associated molecules. We first used a RiboTag approach
      to obtain ribosome-associated transcriptomes from each MSN subtype and found that
      repeated cocaine administration induced Egr3 ribosome-associated mRNA in NAc D1
      MSNs while reducing Egr3 in D2-MSNs. Using Cre-inducible adeno-associated viruses
      combined with D1-Cre and D2-Cre mouse lines, we observed that Egr3 overexpression
      in D1-MSNs enhances rewarding and locomotor responses to cocaine, whereas
      overexpression in D2-MSNs blunts these behaviors. miRNA knock-down of Egr3 in MSN
      subtypes produced opposite behavioral responses from those observed with
      overexpression. Finally, we found that repeated cocaine administration altered
      Egr3 binding to promoters of genes that are important for cocaine-mediated
      cellular and behavioral plasticity. Genes with increased Egr3 binding to
      promoters, Camk2alpha, CREB, FosB, Nr4a2, and Sirt1, displayed increased mRNA in
      D1-MSNs and, in some cases, a reduction in D2-MSNs. Histone and the DNA
      methylation enzymes G9a and Dnmt3a displayed reduced Egr3 binding to their
      promoters and reduced mRNA in D1-MSNs. Our study provides novel insight into an
      opposing role of Egr3 in select NAc MSN subtypes in cocaine action. 

PMID- 25995479
TI  - Delayed activation of spinal microglia contributes to the maintenance of bone
      cancer pain in female Wistar rats via P2X7 receptor and IL-18.
AB  - Accumulating evidence suggests that activation of spinal microglia contributes to
      the development of inflammatory and neuropathic pain. However, the role of spinal
      microglia in the maintenance of chronic pain remains controversial. Bone cancer
      pain shares features of inflammatory and neuropathic pain, but the temporal
      activation of microglia and astrocytes in this model is not well defined. Here,
      we report an unconventional role of spinal microglia in the maintenance of
      advanced-phase bone cancer pain in a female rat model. Bone cancer elicited
      delayed and persistent microglial activation in the spinal dorsal horn on days 14
      and 21, but not on day 7. In contrast, bone cancer induced rapid and persistent
      astrocytic activation on days 7-21. Spinal inhibition of microglia by minocycline
      at 14 d effectively reduced bone cancer-induced allodynia and hyperalgesia.
      However, pretreatment of minocycline in the first week did not affect the
      development of cancer pain. Bone cancer increased ATP levels in CSF, and
      upregulated P2X7 receptor, phosphorylated p38, and IL-18 in spinal microglia.
      Spinal inhibition of P2X7/p-38/IL-18 pathway reduced advanced-phase bone cancer
      pain and suppressed hyperactivity of spinal wide dynamic range (WDR) neurons. IL
      18 induced allodynia and hyperalgesia after intrathecal injection, elicited
      mechanical hyperactivity of WDR neurons in vivo, and increased the frequency of
      mEPSCs in spinal lamina IIo nociceptive synapses in spinal cord slices. Together,
      our findings demonstrate a novel role of microglia in maintaining advanced phase
      cancer pain in females via producing the proinflammatory cytokine IL-18 to
      enhance synaptic transmission of spinal cord nociceptive neurons. 

PMID- 25995481
TI  - Antennal mechanosensory neurons mediate wing motor reflexes in flying Drosophila.
AB  - Although many behavioral studies have shown the importance of antennal
      mechanosensation in various aspects of insect flight control, the identities of
      the mechanosensory neurons responsible for these functions are still unknown. One
      candidate is the Johnston's organ (JO) neurons that are located in the second
      antennal segment and detect phasic and tonic rotations of the third antennal
      segment relative to the second segment. To investigate how different classes of
      JO neurons respond to different types of antennal movement during flight, we
      combined 2-photon calcium imaging with a machine vision system to simultaneously
      record JO neuron activity and the antennal movement from tethered flying fruit
      flies (Drosophila melanogaster). We found that most classes of JO neurons respond
      strongly to antennal oscillation at the wing beat frequency, but not to the tonic
      deflections of the antennae. To study how flies use input from the JO neurons
      during flight, we genetically ablated specific classes of JO neurons and examined
      their effect on the wing motion. Tethered flies flying in the dark require JO
      neurons to generate slow antiphasic oscillation of the left and right wing stroke
      amplitudes. However, JO neurons are not necessary for this antiphasic oscillation
      when visual feedback is available, indicating that there are multiple pathways
      for generating antiphasic movement of the wings. Collectively, our results are
      consistent with a model in which flying flies use JO neurons to detect increases
      in the wing-induced airflow and that JO neurons are involved in a response that
      decreases contralateral wing stoke amplitude. 

PMID- 25995480
TI  - Basolateral amygdala response to food cues in the absence of hunger is associated
      with weight gain susceptibility.
AB  - In rodents, food-predictive cues elicit eating in the absence of hunger
      (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala
      pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this
      circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy
      individuals, we demonstrate here that the amygdala response to the taste of a
      milkshake when sated but not hungry positively predicts weight change. This
      effect is independent of sex, initial BMI, and total circulating ghrelin levels,
      but it is only present in individuals who do not carry a copy of the A1 allele of
      the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2
      receptor density (Blum et al., 1996), show a positive association between caudate
      response and weight change. Regardless of genotype, however, dynamic causal
      modeling supports unidirectional gustatory input from basolateral amygdala (BLA)
      to hypothalamus in sated subjects. This finding suggests that, as in rodents,
      external cues gain access to the homeostatic control circuits of the human
      hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter
      the hypothalamus and drive bidirectional connectivity with the amygdala. These
      findings implicate the BLA-hypothalamic circuit in long-term weight change
      related to nonhomeostatic eating and provide compelling evidence that distinct
      brain mechanisms confer susceptibility to weight gain depending upon individual
      differences in dopamine signaling. 

PMID- 25995483
TI  - Prdm13 regulates subtype specification of retinal amacrine interneurons and
      modulates visual sensitivity.
AB  - Amacrine interneurons, which are highly diversified in morphological,
      neurochemical, and physiological features, play crucial roles in visual
      information processing in the retina. However, the specification mechanisms and
      functions in vision for each amacrine subtype are not well understood. We found
      that the Prdm13 transcriptional regulator is specifically expressed in developing
      and mature amacrine cells in the mouse retina. Most Prdm13-positive amacrine
      cells are Calbindin- and Calretinin-positive GABAergic or glycinergic neurons.
      Absence of Prdm13 significantly reduces GABAergic and glycinergic amacrines,
      resulting in a specific defect of the S2/S3 border neurite bundle in the inner
      plexiform layer. Forced expression of Prdm13 distinctively induces GABAergic and
      glycinergic amacrine cells but not cholinergic amacrine cells, whereas Ptf1a, an
      upstream transcriptional regulator of Prdm13, induces all of these subtypes.
      Moreover, Prdm13-deficient mice showed abnormally elevated spatial, temporal, and
      contrast sensitivities in vision. Together, these results show that Prdm13
      regulates development of a subset of amacrine cells, which newly defines an
      amacrine subtype to negatively modulate visual sensitivities. Our current study
      provides new insights into mechanisms of the diversification of amacrine cells
      and their function in vision. 

PMID- 25995482
TI  - Neurons in the most superficial lamina of the mouse superior colliculus are
      highly selective for stimulus direction.
AB  - The superior colliculus (SC) is a layered midbrain structure important for
      multimodal integration and sensorimotor transformation. Its superficial layers
      are purely visual and receive depth-specific projections from distinct subtypes
      of retinal ganglion cells. Here we use two-photon calcium imaging to characterize
      the response properties of neurons in the most superficial lamina of the mouse
      SC, an undersampled population with electrophysiology. We find that these neurons
      have compact receptive fields with primarily overlapping ON and OFF subregions
      and are highly direction selective. The high selectivity is observed in both
      excitatory and inhibitory neurons. These neurons do not cluster according to
      their direction preference and lack orientation selectivity. In addition, we
      perform single-unit recordings and show that direction selectivity declines with
      depth in the SC. Together, our experiments reveal for the first time a highly
      specialized lamina in the most superficial SC for movement direction, a finding
      that has important implications for understanding signal transformation in the
      early visual system. 

PMID- 25995485
TI  - Time to generalisation as a predictor of prognosis in amyotrophic lateral
      sclerosis.

PMID- 25995484
TI  - A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not
      placodal lineage EGFP expression in a transgenic animal.
AB  - Under physiological conditions, the voltage-gated sodium channel Nav1.8 is
      expressed almost exclusively in primary sensory neurons. The mechanism
      restricting Nav1.8 expression is not entirely clear, but we have previously
      described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the
      tissue-specific expression of Nav1.8 in transfected neurons and cell lines (Puhl
      and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding
      EGFP under the control of this putative sensory neuron specific promoter was
      generated and characterized in this study. Approximately 45% of dorsal root
      ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5
      MUm). The majority of EGFP-positive neurons bound isolectin B4, although a small
      percentage (~10%) colabeled with markers of A-fiber neurons. EGFP expression
      correlated well with the presence of Nav1.8 transcript (95%), Nav1.8
      immunoreactivity (70%), and TTX-R INa (100%), although not all Nav1.8-expressing
      neurons expressed EGFP. Several cranial sensory ganglia originating from
      neurogenic placodes, such as the nodose ganglion, failed to express EGFP,
      suggesting that additional regulatory elements dictate Scn10a expression in
      placodal-derived sensory neurons. EGFP was also detected in discrete brain
      regions of transgenic mice. Quantitative PCR and Nav1.8-immunoreactivity
      confirmed Nav1.8 expression in the amygdala, brainstem, globus pallidus, lateral
      and paraventricular hypothalamus, and olfactory tubercle. TTX-R INa recorded from
      EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic
      line to study novel roles of Nav1.8 beyond sensory neurons. Overall, Scn10a-EGFP
      transgenic mice recapitulate the majority of the Nav1.8 expression pattern in
      neural crest-derived sensory neurons. 

PMID- 25995486
TI  - Homozygous p.V116* mutation in C12orf65 results in Leigh syndrome.
AB  - BACKGROUND: Leigh syndrome (LS) is an early-onset progressive neurodegenerative
      disorder associated with mitochondrial dysfunction. LS is characterised by
      elevated lactate and pyruvate and bilateral symmetric hyperintense lesions in the
      basal ganglia, thalamus, brainstem, cerebral white matter or spinal cord on T2
      weighted MRI. LS is a genetically heterogeneous disease, and to date mutations in
      approximately 40 genes related to mitochondrial function have been linked to the
      disorder. METHODS: We investigated a pair of female monozygotic twins diagnosed
      with LS from consanguineous healthy parents of Indian origin. Their common
      clinical features included optic atrophy, ophthalmoplegia, spastic paraparesis
      and mild intellectual disability. High-blood lactate and high-intensity signal in
      the brainstem on T2-weighted MRI were consistent with a clinical diagnosis of LS.
      To identify the genetic cause of their condition, we performed whole exome
      sequencing. RESULTS: We identified a homozygous nonsense mutation in C12orf65
      (NM_001143905; c.346delG, p.V116*) in the affected twins. Interestingly, the
      identical mutation was previously reported in an Indian family with Charcot-Marie
      Tooth disease type 6, which displayed some overlapping clinical features with the
      twins. CONCLUSIONS: We demonstrate that the identical nonsense mutation in
      C12orf65 can result in different clinical features, suggesting the involvement of
      unknown modifiers.

PMID- 25995487
TI  - Autoantibodies to glutamic acid decarboxylase in patients with epilepsy and their
      relationship with type 1 diabetes: a pilot study.

PMID- 25995488
TI  - Metacognitive function poststroke: a review of definition and assessment.
AB  - Metacognition is the conscious knowledge individuals have about their own
      cognitive capacities and the regulation of these activities through self
      monitoring. The aim of this review was to identify the definitions and assessment
      tools used to examine metacognition in relation to stroke studies. A computer
      database search was conducted using MEDLINE, CINAHL, PsycINFO, Cochrane Reviews,
      Scopus and Web of Science. A total of 1412 publications were retrieved from the
      initial database search. Following the removal of unrelated articles, 34 articles
      remained eligible. 5 studies examined metacognition in relation to cognitive
      and/or emotional functioning, 4 examined the concept in relation to memory, while
      others investigated its relationship to driving, employment or restrictions in
      daily living. 12 studies examined metacognitive function exclusively in stroke.
      Only 1 study examined metacognition in the acute phase of stroke. 7 studies
      adhered to the standard definition of metacognition in line with the
      neuropsychological literature. The main assessment tools utilised included the
      Self-Regulation and Skills Interview (SRSI), the Self-Awareness of Deficits
      Interview (SADI), the Awareness Questionnaire (AQ) and the Patient Competency
      Rating Scale (PCRS). Assessment of metacognition has tended to focus on traumatic
      and other acquired brain injury in comparison to stroke. The majority of the
      studies that examined metacognition in stroke did not assess patients in the
      acute phase. The heterogeneity of assessment tools was in keeping with the
      variation in the definition of metacognition. The emergence of a standard
      metacognitive assessment tool may have important implications for future
      rehabilitative programmes. 

PMID- 25995490
TI  - Accuracy of high-resolution ultrasound in the detection of meniscal tears and
      determination of the visible area of menisci.
AB  - BACKGROUND: Imaging is of great importance in diagnosing meniscal tears. The aim
      of this study was to assess the accuracy of high-resolution ultrasound in the
      diagnosis of meniscal tears, with arthroscopic examination as the standard
      reference, after resolution was confirmed with a target-mounted reference
      phantom. An additional goal was to elucidate the area of the meniscus that could
      be visualized with the same ultrasound machine after placement of markers into
      the menisci of cadaveric knees. METHODS: Seventy patients were included for the
      assessment of the accuracy of a high-resolution ultrasound machine with a 14.0 to
      6.0-MHz linear transducer. The preoperative ultrasound diagnosis, in terms of the
      presence and type of tear, was compared with that in the surgical reports. In the
      cadaveric studies, nine needles were placed in the peripheral zone of the menisci
      at regular intervals and the number of needles that could be observed with the
      system was recorded. RESULTS: The overall sensitivity, specificity, positive
      predictive value, and negative predictive value of ultrasound examination for
      meniscal tears were 88%, 85%, 85%, and 88%, respectively. These statistical
      parameters did not differ significantly between the medial and lateral menisci.
      The sensitivity for diagnosing horizontal, vertical, radial, flap, bucket-handle,
      and complex tears and for detecting discoid lateral menisci was 83%, 64%, 0%,
      64%, 54%, 90%, and 80%, respectively. Ten percent of the lateral menisci could
      not be evaluated because of poor images. The cadaveric studies revealed that the
      ultrasound visualized the entire meniscus except for the anterior horn.
      CONCLUSIONS: The findings of this study suggest that ultrasound examination may
      be suitable for screening for meniscal tears. The fact that almost 10% of the
      lateral menisci could not be evaluated because of poor images appears to be a
      weakness of ultrasound.

PMID- 25995489
TI  - Patient-controlled epidural analgesia or multimodal pain regimen with
      periarticular injection after total hip arthroplasty: a randomized, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: The optimal postoperative analgesia after primary total hip
      arthroplasty remains in question. This randomized, double-blind, placebo
      controlled study compared the use of patient-controlled epidural analgesia (PCEA)
      with use of a multimodal pain regimen including periarticular injection (PAI). We
      hypothesized that PAI would lead to earlier readiness for discharge, decreased
      opioid consumption, and lower pain scores. METHODS: Forty-one patients received
      PAI, and forty-three patients received PCEA. Preoperatively, both groups were
      administered dexamethasone (6 mg, orally). The PAI group received a clonidine
      patch and sustained-release oxycodone (10 mg), while the PCEA group had placebo.
      Both groups received combined spinal-epidural anesthesia and used an epidural
      pain pump postoperatively; the PAI group had normal saline solution, while the
      PCEA group had bupivacaine and hydromorphone. The primary outcome, readiness for
      discharge, required the discontinuation of the epidural, a pain score of <4
      (numeric rating scale) without parenteral narcotics, normal eating, minimal
      nausea, urination without a catheter, a dry surgical wound, no acute medical
      problems, and the ability to independently transfer and walk 12.2 m (40 ft).
      RESULTS: The mean time to readiness for discharge (and standard deviation) was
      2.4 +/- 0.7 days (PAI) compared with 2.3 +/- 0.8 days (PCEA) (p = 0.86). The mean
      length of stay was 3.0 +/- 0.8 days (PAI) compared with 3.1 +/- 0.7 days (PCEA)
      (p = 0.46). A significant mean difference in pain score of 0.74 with ambulation
      (p = 0.01; 95% confidence interval [CI], 0.18 to 1.31) and 0.80 during physical
      therapy (p = 0.03; 95% CI, 0.09 to 1.51) favored the PCEA group. The mean opioid
      consumption (oral morphine equivalents in milligrams) was significantly higher in
      the PAI group on postoperative day 0 (43 +/- 21 compared with 28 +/- 23; p =
      0.002) and postoperative days 0 through 2 (136 +/- 59 compared with 90 +/- 79; p
      = 0.004). Opioid-Related Symptom Distress Scale (ORSDS) composite scores for
      severity and bothersomeness as well as scores for nausea, vomiting, and itchiness
      were significantly higher in the PCEA group (p < 0.05). Quality of Recovery-40
      scores and patient satisfaction were similar. CONCLUSIONS: PAI did not decrease
      the time to discharge and was associated with higher pain scores and greater
      opioid consumption but lower ORSDS scores compared with PCEA. The choice for
      analgesic regimen may depend on a particular patient's threshold for pain and the
      potential side effects.

PMID- 25995492
TI  - Minimal clinically important difference and the effect of clinical variables on
      the ankle osteoarthritis scale in surgically treated end-stage ankle arthritis.
AB  - BACKGROUND: There is much debate regarding the best outcome tool for use in foot
      and ankle surgery, specifically in patients with ankle arthritis. The Ankle
      Osteoarthritis Scale (AOS) is a validated, disease-specific score. The goals of
      this study were to investigate the clinical performance of the AOS and to
      determine a minimal clinically important difference (MCID) for it, using a large
      cohort of 238 patients undergoing surgery for end-stage ankle arthritis. METHODS:
      Patients treated with total ankle arthroplasty or ankle arthrodesis were
      prospectively followed for a minimum of two years at a single site. Data on
      demographics, comorbidities, AOS score, Short Form-36 results, and the
      relationship between expectations and satisfaction were collected at baseline
      (preoperatively), at six and twelve months, and then yearly thereafter. A linear
      regression analysis examined the variables affecting the change in AOS scores
      between baseline and the two-year follow-up. An MCID in the AOS change score was
      then determined by employing an anchor question, which asked patients to rate
      their relief from symptoms after surgery. RESULTS: Surgical treatment of end
      stage ankle arthritis resulted in a mean improvement (and standard deviation) of
      31.2 +/- 22.7 points in the AOS score two years after surgery. The MCID of the
      AOS change score was a mean of 28.0 +/- 17.9 points. The change in AOS score was
      significantly affected by the preoperative AOS score, smoking, back pain, and
      age. CONCLUSIONS: Patients undergoing arthroplasty or arthrodesis for end-stage
      ankle arthritis experienced a mean improvement in AOS score that was greater than
      the estimated MCID (31.2 versus 28.0 points).

PMID- 25995491
TI  - The cost-effectiveness of surgical treatment of medial unicompartmental knee
      osteoarthritis in younger patients: a computer model-based evaluation.
AB  - BACKGROUND: Surgical options for the management of medial compartment
      osteoarthritis of the varus knee include high tibial osteotomy, unicompartmental
      knee arthroplasty, and total knee arthroplasty. We sought to determine the cost
      effectiveness of high tibial osteotomy and unicompartmental knee arthroplasty as
      alternatives to total knee arthroplasty for patients fifty to sixty years of age.
      METHODS: We built a probabilistic state-transition computer model with health
      states defined by pain, postoperative complications, and subsequent surgical
      procedures. We estimated transition probabilities from published literature.
      Costs were determined from Medicare reimbursement schedules. Health outcomes were
      measured in quality-adjusted life-years (QALYs). We conducted analyses over
      patients' lifetimes from the societal perspective, with health and cost outcomes
      discounted by 3% annually. We used probabilistic sensitivity analyses to account
      for uncertainty in data inputs. RESULTS: The estimated discounted QALYs were
      14.62, 14.63, and 14.64 for high tibial osteotomy, unicompartmental knee
      arthroplasty, and total knee arthroplasty, respectively. Discounted total direct
      medical costs were $20,436 for high tibial osteotomy, $24,637 for
      unicompartmental knee arthroplasty, and $24,761 for total knee arthroplasty (in
      2012 U.S. dollars). The incremental cost-effectiveness ratio (ICER) was $231,900
      per QALY for total knee arthroplasty and $420,100 per QALY for unicompartmental
      knee arthroplasty. Probabilistic sensitivity analyses showed that, at a
      willingness-to-pay (WTP) threshold of $50,000 per QALY, high tibial osteotomy was
      cost-effective 57% of the time; total knee arthroplasty, 24%; and
      unicompartmental knee arthroplasty, 19%. At a WTP threshold of $100,000 per QALY,
      high tibial osteotomy was cost-effective 43% of time; total knee arthroplasty,
      31%; and unicompartmental knee arthroplasty, 26%. CONCLUSIONS: In fifty to sixty
      year-old patients with medial unicompartmental knee osteoarthritis, high tibial
      osteotomy is an attractive option compared with unicompartmental knee
      arthroplasty and total knee arthroplasty. This finding supports greater
      utilization of high tibial osteotomy for these patients. The cost-effectiveness
      of high tibial osteotomy and of unicompartmental knee arthroplasty depend on
      rates of conversion to total knee arthroplasty and the clinical outcomes of the
      conversions.

PMID- 25995493
TI  - Association between patient-reported measures of psychological distress and
      patient satisfaction scores after spine surgery.
AB  - BACKGROUND: Patient satisfaction has become an important component of the
      delivery of health care in the United States. Previous studies have shown that
      patient satisfaction is influenced by patient-specific characteristics. The goal
      of this study was to determine whether psychological distress influences
      outpatient satisfaction scores following spine surgery. METHODS: We
      retrospectively reviewed the records from all outpatient clinical encounters at a
      single academic spine surgery center between February 2011 and January 2013. Any
      patient who completed both a patient satisfaction survey and a Distress and Risk
      Assessment Method (DRAM) questionnaire for the same clinical encounter was
      included in the study. Statistical analysis was performed to determine whether
      patient satisfaction scores were influenced by psychological distress. RESULTS:
      During the study period, 103 patients who met the inclusion criteria were
      identified. On the basis of their responses to the DRAM questionnaire, fifty-six
      were classified as normal (no evidence of distress), twenty-two as at risk,
      thirteen as distressed depressive, and twelve as distressed somatic. The mean
      overall patient satisfaction scores (and standard deviation) were 90.2 +/- 10.9
      in the normal group, 94.7 +/- 8.2 in the at-risk group, 87.5 +/- 16.2 in the
      distressed-depressive group, and 75.7 +/- 22.4 in the distressed-somatic group (p
      = 0.003). The mean score for the patients' satisfaction with their provider was
      94.2 +/- 12.0 in the normal group, 94.2 +/- 9.5 in the at-risk group, 90.6 +/-
      24.0 in the distressed-depressive group, and 74.9 +/- 26.2 in the distressed
      somatic group (p = 0.011). CONCLUSIONS: These results indicate a significant
      association between patient satisfaction and psychological distress as measured
      with the DRAM questionnaire. "Distressed" patients gave significantly lower
      scores for overall satisfaction and satisfaction with their provider compared
      with patients categorized as "normal." These results suggest that psychological
      factors may influence patients' perception of the medical care provided to them.

PMID- 25995494
TI  - Health economic implications of perioperative delirium in older patients after
      surgery for a fragility hip fracture.
AB  - BACKGROUND: Patients who experience a fragility hip fracture are at high risk for
      perioperative delirium. The purpose of the present study was to evaluate the
      impact, from a hospital perspective, of perioperative delirium on the length of
      the hospital stay and episode-of-care costs for elderly patients who underwent
      surgical treatment of a fragility hip fracture. METHODS: A total of 242 patients
      sixty-five years of age or older (mean age, eighty-two years; range, sixty-five
      to 103 years) who underwent surgical treatment of a fragility hip fracture at a
      single center between January 2011 and December 2012 were evaluated. Demographic,
      clinical, surgical, and adverse-events data were extracted and analyzed. The
      confusion assessment method (CAM) was used prospectively to detect perioperative
      delirium. RESULTS: One hundred and sixteen (48%) of the 242 patients developed
      perioperative delirium during their stay in the hospital. Compared with patients
      with no delirium, delirium was associated with a mean incremental total length of
      hospital stay of 7.4 days (95% confidence interval [CI] = 3.7 to 11.2 days; p <
      0.001), a mean incremental length of stay following surgery of 7.4 days (95% CI =
      3.8 to 11.1 days; p < 0.001), and a mean incremental episode-of-care cost (in
      2012 Canadian dollars) of $8286 (95% CI = $3690 to $12,881; p < 0.001). The total
      incremental episode-of-care cost attributable to delirium over the study period
      was $961,131 in 2012 Canadian dollars. CONCLUSIONS: Nearly 50% of elderly
      patients who underwent surgery for a fragility hip fracture developed
      perioperative delirium, which was associated with a significant incremental in
      hospital length of stay and significant incremental episode-of-care costs. These
      findings highlight the importance of implementing cost-effective interventions to
      reduce the prevalence of perioperative delirium in elderly patients with a low
      energy hip fracture.

PMID- 25995496
TI  - Detection of a traumatic arthrotomy in the pediatric knee using the saline
      solution load test.
AB  - BACKGROUND: The objective of this study was to quantify the load volume needed
      for a positive diagnosis of a traumatic arthrotomy in the pediatric knee with use
      of the saline solution load test (SLT). METHODS: From February 2013 to June 2014,
      eighty-seven pediatric patients who were undergoing elective knee arthroscopy
      were prospectively enrolled in this study. An SLT was performed in each patient
      using a 5-mm superolateral portal as the arthrotomy site, with injection of the
      saline solution into the lateral aspect of the knee. The 50th, 75th, 90th, and
      95th percentiles of saline solution load volume required for a positive result
      were identified. Univariate linear regression was used to identify possible
      relationships between demographics (age, height, weight, and body mass index
      [BMI]) and load volume. RESULTS: Forty-one female and forty-six male patients
      with a mean age (and standard deviation) of 13.4 +/- 3.0 years (range, five to
      eighteen years) and a mean BMI of 21.9 +/- 5.0 kg/m(2) (range, 12.9 to 36.2
      kg/m(2)) were enrolled. The mean saline solution load volume was 28.9 +/- 14.2 mL
      (range, 7.0 to 78 mL). The 50th, 75th, 90th, and 95th percentiles of saline
      solution load volume were 27, 37, 47, and 58 mL, respectively. The mean load
      volume did not differ significantly between male and female patients (28.8 +/-
      13.9 versus 29.0 +/- 14.7 mL, respectively; p = 0.92). Load volume was
      significantly correlated with age, height, weight, and BMI. CONCLUSIONS: On the
      basis of our findings, a saline solution load volume of 47 mL is required to
      detect 90% of superolateral traumatic arthrotomies of 5 mm in the pediatric knee
      with use of the SLT.

PMID- 25995495
TI  - Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to
      2009.
AB  - BACKGROUND: The epidemiology of osteomyelitis in the United States is largely
      unknown. The purpose of this study was to determine long-term secular trends in
      the incidence of osteomyelitis in a population-based setting. METHODS: The study
      population comprised 760 incident cases of osteomyelitis first diagnosed between
      January 1, 1969, and December 31, 2009, among residents of Olmsted County,
      Minnesota. The complete medical records for each potential subject were reviewed
      to confirm the osteomyelitis diagnosis and to extract details on anatomical
      sites, infecting organisms, etiological risk factors, and outcomes. RESULTS: The
      overall age and sex-adjusted annual incidence of osteomyelitis was 21.8 cases per
      100,000 person-years. The annual incidence was higher for men than for women and
      increased with age (p < 0.001). Rates increased with the calendar year (p <
      0.001) from 11.4 cases per 100,000 person-years in the period from 1969 to 1979
      to 24.4 per 100,000 person-years in the period from 2000 to 2009. The incidence
      remained relatively stable among children and young adults but almost tripled
      among individuals older than sixty years; this was partly driven by a significant
      increase in diabetes-related osteomyelitis from 2.3 cases per 100,000 person
      years in the period from 1969 to 1979 to 7.6 cases per 100,000 person-years in
      the period from 2000 to 2009 (p < 0.001). Forty-four percent of cases involved
      Staphylococcus aureus infections. CONCLUSIONS: The reasons for the increase in
      osteomyelitis between 1969 and 2009 are unclear but could comprise a variety of
      factors, including changes in diagnosing patterns or increases in the prevalence
      of risk factors (e.g., diabetes) in this population.

PMID- 25995497
TI  - Transtrapezial Approach for Fixation of Acute Scaphoid Fractures: Rationale,
      Surgical Techniques, and Results: AAOS Exhibit Selection.
AB  - The ideal position for a screw used for scaphoid fixation is central. The purpose
      of this study was to compare the current volar percutaneous approaches used for
      scaphoid fracture fixation, explore different options to improve central screw
      placement, and describe our experience with the transtrapezial approach. 

PMID- 25995498
TI  - Volar locking-plate and Kirschner-wire fixation did not differ in terms of
      functional outcomes after dorsally displaced distal radial fracture.

PMID- 25995499
TI  - Incision in the Quadriceps of >4 cm Delayed Recovery of Strength After Total Knee
      Replacement.

PMID- 25995500
TI  - Reverse shoulder arthroplasty provided better functional outcomes than
      hemiarthroplasty for acute proximal humeral fractures.

PMID- 25995501
TI  - What's New in Foot and Ankle Surgery.

PMID- 25995502
TI  - Graduates of Orthopaedic Residency Training Are Increasingly Subspecialized: A
      Review of the American Board of Orthopaedic Surgery Part II Database.
AB  - BACKGROUND: Orthopaedic fellowships first gained popularity in the U.S. in the
      1970s, and since that time, the percentage of orthopaedic residency graduates
      pursuing subspecialty fellowship training has increased. Prior reports have shown
      an increase in subspecialization from 1988 through 2002; however, the current
      number and proportion of graduates pursuing fellowship training since 2002 are
      unknown. The purpose of this study was to determine the percentage of recent
      graduates who pursue fellowship training and the proportion of procedures that
      these graduates perform within their area of fellowship training. METHODS: Data
      from the American Board of Orthopaedic Surgery Part II examination for board
      certification were used to determine the number and percentage of fellowship
      trained and non-fellowship-trained applicants from 2003 to 2013. The percentage
      of cases performed by fellowship-trained applicants within their area of
      fellowship training was calculated and was analyzed as a function of time and a
      function of fellowship training category. Linear regression was used to determine
      trend as a function of time. RESULTS: The percentage of fellowship-trained
      applicants increased from 76% in 2003 to 90% in 2013. Of the 1,257,161 procedures
      performed by fellowship-trained applicants, 981,077 (78%) were performed within
      the surgeon's area of fellowship training. Spine and hand-trained applicants
      performed more than 85% of their procedures within their area of fellowship
      training. CONCLUSIONS: From 2003 to 2013, the percentage of fellowship-trained
      applicants taking the American Board of Orthopaedic Surgery Part II examination
      gradually increased to 90%. In the same time period, fellowship-trained surgeons
      performed an increasing proportion of procedures within their area of
      subspecialty training. Orthopaedic graduates have become increasingly
      subspecialized over the past decade.

PMID- 25995503
TI  - Patient-Controlled Epidural Analgesia After Total Hip Arthroplasty: Ready for
      Prime Time?

PMID- 25995504
TI  - I Am Not an Economist, But...

PMID- 25995505
TI  - New Findings Highlight the Misdirected Utilization of Patient Satisfaction
      Surveys and the Importance of Patient Psychology in General Medical Care.

PMID- 25995506
TI  - Enhancing discourse in AJPE.

PMID- 25995507
TI  - Should a pharmacy dean be a pharmacist?

PMID- 25995508
TI  - Should a pharmacy dean be a pharmacist?

PMID- 25995509
TI  - Reframing our pursuit of life balance.
AB  - During our time in the 2013 Academic Leadership Fellows Program, we explored what
      it takes to achieve life balance through a framework presented in a Harvard
      Business Review article. In this Statement, we describe 5 different areas from
      the article that provide infrastructure for reflecting on how we have learned to
      approach life balance in academia. We also provide brief messages based on this
      reading and others to help academics' pursuit of life balance. 

PMID- 25995510
TI  - An international comparison study of pharmacy students' achievement goals and
      their relationship to assessment type and scores.
AB  - OBJECTIVE: To identify pharmacy students' preferred achievement goals in a multi
      national undergraduate population, to investigate achievement goal preferences
      across comparable degree programs, and to identify relationships between
      achievement goals, academic performance, and assessment type. METHODS: The
      Achievement Goal Questionnaire was administered to second year students in 4
      universities in Australia, New Zealand, England, and Wales. Academic performance
      was measured using total scores, multiple-choice questions, and written answers
      (short essay). RESULTS: Four hundred eighty-six second year students
      participated. Students showed an overall preference for the mastery-approach goal
      orientation across all sites. The predicted relationships between goal
      orientation and multiple-choice questions, and written answers scores, were
      significant. CONCLUSION: This study is the first of its kind to examine pharmacy
      students' achievement goals at a multi-national level and to differentiate
      between assessment type and measures of achievement motivation. Students adopting
      a mastery-approach goal are more likely to gain high scores in assessments that
      measure understanding and depth of knowledge.

PMID- 25995511
TI  - The sustainability of improvements from continuing professional development in
      pharmacy practice and learning behaviors.
AB  - OBJECTIVE: To assess the long-term sustainability of continuing professional
      development (CPD) training in pharmacy practice and learning behaviors. METHODS:
      This was a 3-year posttrial survey of pharmacists who had participated in an
      unblinded randomized controlled trial of CPD. The online survey assessed
      participants' perceptions of pharmacy practice, learning behaviors, and
      sustainability of CPD. Differences between groups on the posttrial survey
      responses and changes from the trial's follow-up survey to the posttrial survey
      responses within the intervention group were compared. RESULTS: Of the 91
      pharmacists who completed the original trial, 72 (79%) participated in the
      sustainability survey. Compared to control participants, a higher percentage of
      intervention participants reported in the sustainability survey that they had
      utilized the CPD concept (45.7% vs 8.1%) and identified personal learning
      objectives (68.6% vs 43.2%) during the previous year. Compared to their follow-up
      survey responses, lower percentages of intervention participants reported
      identifying personal learning objectives (94.3% vs 68.6%), documenting their
      learning plan (82.9% vs 22.9%) and participating in learning by doing (42.9% vs
      14.3%) in the sustainability survey. In the intervention group, many of the
      improvements to pharmacy practice items were sustained over the 3-year period but
      were not significantly different from the control group. CONCLUSION:
      Sustainability of a CPD intervention over a 3-year varied. While CPD-trained
      pharmacists reported utilizing CPD concepts at a higher rate than control
      pharmacists, their CPD learning behaviors diminished over time.

PMID- 25995512
TI  - Integration of an online simulated prescription analysis into undergraduate
      pharmacy teaching using supplemental and replacement models.
AB  - OBJECTIVE: To describe student use and perceptions of online simulated
      prescription analysis following integration of supplemental and replacement
      models into pharmacy practice teaching. METHODS: Strathclyde Computerized
      Randomized Interactive Prescription Tutor (SCRIPT) is a simulated prescription
      analysis tool designed to support a pharmacy practice competency class. In 2008
      2009, SCRIPT scenarios were released to coincide with timetabled teaching as the
      supplemental model. In 2009-2010, SCRIPT also replaced one-sixth of the taught
      component of the class as the replacement model. Student use and performance were
      compared, and their perceptions were documented. RESULTS: In both cohorts, the
      majority of use (over 70%) occurred immediately before assessments. Remote access
      decreased from 6409 (supplemental) to 3782 (replacement) attempts per 100
      students. There was no difference in student performance between the cohorts,
      Students reported group and individual use and 4 targeted approaches using
      SCRIPT. CONCLUSION: E-learning can reduce the staff time in pharmacy practice
      teaching without affecting student performance. SCRIPT permits flexible learning
      that suits student preferences.

PMID- 25995513
TI  - Pharmacy residents' pursuit of academic positions.
AB  - OBJECTIVE: To describe pharmacy residents' interest in and pursuit of academic
      positions. METHODS: An electronic presurvey and postsurvey were sent to pharmacy
      residents during the 2011-2012 residency year. The initial survey evaluated
      residents' job preferences and interest in academia at the beginning of
      residency, and the follow-up survey focused on job selection and reasons for
      pursuing or not pursuing positions in academia. RESULTS: Nine hundred thirty-six
      residents responded to the initial survey and 630 participated in both the
      initial and follow-up survey. Forty-eight percent of those responding to both
      surveys strongly considered a career in academia in the initial survey, 28%
      applied for an academic position, and 7% accepted a position. Second-year
      postgraduate residents were more likely than first-year postgraduate residents to
      apply for and be offered a faculty position. CONCLUSION: Pharmacy residents are
      interested in academia. While increasing interest among residents is encouraging
      for faculty recruitment, the academy should also encourage and develop adequate
      training experiences to prepare residents to succeed in these positions.

PMID- 25995514
TI  - National trends in IPPE programs at US schools of pharmacy from 2008-2013.
AB  - OBJECTIVE: To determine trends and challenges in introductory pharmacy practice
      experience (IPPE) programs from 2008-2013. METHODS: In 2013, a web-based survey
      was sent to IPPE program administrators at 107 fully accredited colleges and
      schools of pharmacy. The survey addressed administrative personnel, program
      structure, and quality assurance issues. RESULTS: Sixty-nine IPPE administrators
      responded to the survey (64.5% response rate). Within the past 5 years, 4
      significant trends occurred in the area of administrative personnel, 7 trends in
      program structure, and 6 in quality assurance. CONCLUSION: Clarifications of ACPE
      Standards through new guidelines and policy statements likely influence many of
      the 17 trends. Understaffed programs, competition for institutional sites,
      difficulty conducting site visits, preceptor training, program assessment,
      documentation maintenance, and individual site requirements are all challenges.
      The results of this study can be used as a stimulus to address ongoing issues and
      to enhance the quality of IPPE programs.

PMID- 25995515
TI  - Interactive web-based learning modules prior to general medicine advanced
      pharmacy practice experiences.
AB  - OBJECTIVE: To implement and evaluate interactive web-based learning modules prior
      to advanced pharmacy practice experiences (APPEs) on inpatient general medicine.
      DESIGN: Three clinical web-based learning modules were developed for use prior to
      APPEs in 4 health care systems. The aim of the interactive modules was to
      strengthen baseline clinical knowledge before the APPE to enable the application
      of learned material through the delivery of patient care. ASSESSMENT: For the
      primary endpoint, postassessment scores increased overall and for each individual
      module compared to preassessment scores. Postassessment scores were similar among
      the health care systems. The survey demonstrated positive student perceptions of
      this learning experience. CONCLUSION: Prior to inpatient general medicine APPEs,
      web-based learning enabled the standardization and assessment of baseline student
      knowledge across 4 health care systems.

PMID- 25995516
TI  - An online health informatics elective course for doctor of pharmacy students.
AB  - OBJECTIVE: To describe the development and assessment of an online elective
      health informatics course and determine its potential for universal integration
      into doctor of pharmacy (PharmD) curricula. DESIGN: A 2-credit hour online
      elective course was developed and offered to all PharmD students; voiced-over
      Powerpoint lectures were used to deliver content. ASSESSMENT: Assessment of
      student performance was measured using quantitative metrics via discussion
      questions, quizzes, written papers, and examinations. Qualitative findings were
      measured through discussion questions, a goal-setting classroom assessment
      technique, and an end-of-course reflection. Students report finding value in the
      course and recognizing how the knowledge gained could impact their future
      practice as pharmacists. CONCLUSION: An online course in health informatics can
      be an effective way to deliver content and provide a blueprint for continued
      integration of the content into curricula.

PMID- 25995517
TI  - Assessing empathy and self-efficacy levels of pharmacy students in an elective
      diabetes management course.
AB  - OBJECTIVE: To assess the impact of a 6-week patient/provider interaction
      simulation on empathy and self-efficacy levels of diabetes management skills in
      third-year pharmacy students. DESIGN: Pharmacy students enrolled in a diabetes
      elective course were paired to act as a patient with diabetes or as a provider
      assisting in the management of that patient during a 6-week simulation activity.
      After 3 weeks, students switched roles. The simulation was designed with
      activities to build empathy. ASSESSMENT: The Jefferson Scale of Empathy (JSE) and
      a self-efficacy survey were administered to assess change in empathy and
      confidence levels from baseline to the end of the activity. Completion of the
      activity resulted in significant improvement in total JSE scores. Additionally,
      significant improvements in overall self-efficacy scores regarding diabetes
      management were noted. CONCLUSION: The 6-week patient/provider interaction
      simulation improved empathy and self-efficacy levels in third-year pharmacy
      students.

PMID- 25995518
TI  - Design and implementation of a laboratory-based drug design and synthesis
      advanced pharmacy practice experience.
AB  - OBJECTIVE: To provide students with an opportunity to participate in medicinal
      chemistry research within the doctor of pharmacy (PharmD) curriculum. DESIGN: We
      designed and implemented a 3-course sequence in drug design or drug synthesis for
      pharmacy students consisting of a 1-month advanced elective followed by two 1
      month research advanced pharmacy practice experiences (APPEs). To maximize
      student involvement, this 3-course sequence was offered to third-year and fourth
      year students twice per calendar year. ASSESSMENT: Students were evaluated based
      on their commitment to the project's success, productivity, and professionalism.
      Students also evaluated the course sequence using a 14-item course evaluation
      rubric. Student feedback was overwhelmingly positive. Students found the
      experience to be a valuable component of their pharmacy curriculum. CONCLUSION:
      We successfully designed and implemented a 3-course research sequence that allows
      PharmD students in the traditional 4-year program to participate in drug design
      and synthesis research. Students report the sequence enhanced their critical
      thinking and problem-solving skills and helped them develop as independent
      learners. Based on the success achieved with this sequence, efforts are underway
      to develop research APPEs in other areas of the pharmaceutical sciences.

PMID- 25995519
TI  - Developing pharmacy student communication skills through role-playing and active
      learning.
AB  - OBJECTIVE: To evaluate the impact on pharmacy students of a communication course,
      which used role-playing to develop active-learning skills. DESIGN: Students role
      playing pharmacists in patient care scenarios were critiqued by students and
      pharmacist faculty members. Grading was performed using the rubric inspired by
      Bruce Berger's Communication Skills for Pharmacists. Written skills were
      evaluated using student written critique questionnaires. Students completed
      precourse and postcourse self-assessment surveys. Preceptor evaluations were
      analyzed for course impact. ASSESSMENT: Students demonstrated improvement in oral
      skills based on role-play scores (45.87/50) after practice sessions. The average
      score based on the student questionnaire was 9.31/10. Gain was demonstrated in
      all defined course objectives. Impact on introductory pharmacy practice
      experience (IPPE) communication objectives was insignificant. Student evaluations
      for course and teaching strategy reflected a high average. CONCLUSION: Study
      results demonstrated improvement in oral and written communication skills that
      may help improve interprofessional teamwork between pharmacists and other health
      care providers.

PMID- 25995520
TI  - Pillars and foundations of quality for continuing education in pharmacy.

PMID- 25995521
TI  - The Effect of Educational Attainment on Adult Mortality in the United States.

PMID- 25995523
TI  - High-Pressure Synthesis and Crystal Structure of Ce4B14O27.
AB  - Ce4B14O27 was synthesized under conditions of 2.6 GPa and 750  degrees C in a
      Walker-type multianvil apparatus. The crystal structure was determined on the
      basis of single-crystal X-ray diffraction data, collected at room temperature,
      revealing that Ce4B14O27 is isotypic to La4B14O27. Ce4B14O27 crystallizes
      monoclinically with four formula units in the space group C2/c (No. 15) and the
      lattice parameters a = 1117.8(2), b = 640.9(2), c = 2531.7(5) pm, and beta =
      100.2(1) degrees . The three-dimensional boron-oxygen framework consists of
      [BO4]5- tetrahedra and trigonal-planar [BO3]3- groups. The structure contains two
      crystallographically different cerium ions. Furthermore, Raman spectroscopy was
      performed on single crystals of Ce4B14O27.

PMID- 25995522
TI  - Topological Properties of Chemical Bonds from Static and Dynamic Electron
      Densities.
AB  - Dynamic and static electron densities (EDs) based on the independent spherical
      atom model (IAM) and multipole (MP) models of crambin were successfully computed,
      holding no series-termination effects. The densities are compared to EDs of small
      biological molecules at diverse temperatures. It is outlined that proteins
      exhibit an intrinsic flexibility, present as frozen disorder at 100 K, in
      contrast to small molecules. The flexibility of the proteins is reflected by
      atomic displacement parameters (B-factors), which are considerably larger than
      for small molecules at 298 K. Thus, an optimal deconvolution of deformation
      density and thermal motion is not guaranteed, which prevents a free refinement of
      MP parameters but allows an application of transferable, fixed MP parameters. The
      analysis of the topological properties, such as the density at bond critical
      points (BCPs) and the Laplacian, reveals systematic differences between static
      and dynamic EDs. Zero-point-vibrations, yet present in dynamic EDs at low
      temperature, affect but marginally the EDs of small molecules. The zero-point
      vibrations cause a smearing of the ED, which becomes more pronounced with
      increasing temperature. Topological properties, primarily the Laplacian, of
      covalent bonds appear to be more sensitive to effects by temperature and the
      polarity of the bonds. However, dynamic EDs at ca. 20 K based on MP models
      provide a good characterization of chemical bonding. Both the density at BCPs and
      the Laplacian of hydrogen bonds constitute similar values from static and dynamic
      EDs for all studied temperatures. Deformation densities demonstrate the necessity
      of the employment of MP parameters in order to comprise the nature of covalent
      bonds. The character of hydrogen bonds can be roughly pictured by IAM, whereas MP
      parameters are recommended for a classification of hydrogen bonds beyond a solely
      interpretation of topological properties.

PMID- 25995524
TI  - Conformational Study of an Artificial Metal-Dependent Regulation Site for Use in
      Designer Proteins.
AB  - This report describes the dimerisation of glutathione, and by extension, other
      cysteine-containing peptides or protein fragments, with a 5, 5'-disubstituted-2,
      2'-bipyridine or 6, 6"-disubstituted-2, 2':6',2"-terpyridine unit. The resulting
      bipy-GS2 and terpy-GS2 were investigated as potential metal ion dependent
      switches in aqueous solution, and were found to predominantly adopt the transoid
      conformation at physiological pH. Metal complexation with CuII and ZnII at this
      pH has been studied by UV/Vis, CD, NMR and ion-mobility mass spectrometry. ZnII
      titrations are consistent with the formation of a 1:1 ZnII:terpy-GS2 complex at
      pH 7.4, but bipy-GS2 was shown to form both 1:1 and 1:2 complexes with the former
      being predominant under dilute micromolar conditions. Formation constants for the
      resulting 1:1 complexes were determined to be log KM 6.86 (bipy-GS2 ) and 6.22
      (terpy-GS2 ), consistent with a higher affinity for the unconstrained bipyridine,
      compared to the strained terpyridine. CuII coordination involves the initial
      formation of 1:1 complexes, followed by 1.5Cu:1bipy-GS2 and 2Cu:1terpy-GS2
      complexes at micromolar concentrations. Binding constants for formation of the
      1:1 complexes (log KM 12.5 (bipy-GS2 ); 8.04 and 7.14 (terpy-GS2 )) indicate a
      higher affinity for CuII than ZnII. Finally, ion-mobility MS studies detected the
      free ligands in their protonated form, and were consistent with the formation of
      two different Cu adducts with different conformations in the gas-phase. We
      illustrate that the bipyridine and terpyridine dimerisation units can behave like
      conformational switches in response to Cu/Zn complexation, and propose that in
      future these can be employed in synthetic biology with larger peptide or protein
      fragments, to control large scale folding and related biological function.

PMID- 25995526
TI  - Two Decades of Negative Educational Selectivity of Mexican Migrants to the United
      States.
AB  - : Immigration is commonly considered to be selective of more able individuals.
      Studies comparing the educational attainment of Mexican immigrants in the United
      States to that of the Mexican resident population support this characterization.
      Upward educational-attainment biases in both coverage and measurement, however,
      may be substantial in U.S. DATA SOURCES:  Moreover, differences in educational
      attainment by place size are very large within Mexico, and U.S. data sources
      provide no information on immigrants' places of origin within Mexico. To address
      these problems, we use multiple sources of nationally-representative Mexican
      survey data to re-evaluate the educational selectivity of working-age Mexican
      migrants to the United States over the 1990s and 2000s. We document
      disproportionately rural and small-urban-area origins of Mexican migrants and a
      steep positive gradient of educational attainment by place size. We show that
      together these conditions induced strongly negative educational selection of
      Mexican migrants throughout the 1990s and 2000s. We interpret this finding as
      consistent with low returns to the education of unauthorized migrants and few
      opportunities for authorized migration.

PMID- 25995525
TI  - Population Changes in a Community of Alkaliphilic Iron-Reducing Bacteria Due to
      Changes in the Electron Acceptor: Implications for Bioremediation at Alkaline
      Cr(VI)-Contaminated Sites.
AB  - A serial enrichment culture has been grown in an alkaline Fe(III)-citrate
      containing medium from an initial inoculum from a soil layer beneath a chromium
      ore processing residue (COPR) disposal site where Cr(III) is accumulating from
      Cr(VI) containing leachate. This culture is dominated by two bacterial genera in
      the order Clostridiales, Tissierella, and an unnamed Clostridium XI subgroup.
      This paper investigates the growth characteristics of the culture when Cr(VI) is
      added to the growth medium and when aquifer sand is substituted for Fe(III)
      citrate. The aim is to determine how the availability and chemical form of
      Fe(III) affects the growth of the bacterial consortium, to determine the impact
      of Cr(VI) on growth, and thus attempt to understand the factors that are
      controlling Cr(III) accumulation beneath the COPR site. The culture can grow
      fermentatively at pH 9.2, but growth is stronger when it is associated with
      Fe(III) reduction. It can withstand Cr(VI) in the medium, but growth only occurs
      once Cr(VI) is removed from solution. Cr(VI) reduced the abundance of Tissierella
      sp. in the culture, whereas the Clostridium XI sp. was Cr(VI) tolerant. In
      contrast, growth with solid phase Fe(III)-oxyhydroxides (present as coatings on
      aquifer sand) favoured the Tissierella C sp., possibly because it produces
      riboflavin as an extracellular electron shuttling compound allowing more
      efficient electron transfer to solid Fe(III) phases. Thus, it is suggested that
      bacterially mediated Cr(III) reduction in the soil beneath the COPR site is
      dependent on Fe(III) reduction to sustain the bacterial community.

PMID- 25995527
TI  - Statistical relationships between journal use and research output at academic
      institutions in South Korea.
AB  - In this study, we analysed the statistical association between e-journal use and
      research output at the institution level in South Korea by performing comparative
      and diachronic analyses, as well as the analysis by field. The datasets were
      compiled from four different sources: national reports on research output
      indicators in science fields, two statistics databases on higher education
      institutions open to the public, and e-journal usage statistics generated by 47
      major publishers. Due to the different data sources utilized, a considerable
      number of missing values appeared in our datasets and various mapping issues
      required corrections prior to the analysis. Two techniques for handling missing
      data were applied and the impact of each technique was discussed. In order to
      compile the institutional data by field, journals were first mapped, and then the
      statistics were summarized according to subject field. We observed that e-journal
      use exhibited stronger correlations with the number of publications and the times
      cited, in contrast to the number of undergraduates, graduates, faculty members
      and the amount of research funds, and this was the case regardless of the NA
      handling method or author type. The difference between the maximum correlation
      for the amount of external research funding with two average indicators and that
      of the correlation for e-journal use were not significant. Statistically, the
      accountability of e-journal use for the average times cited per article and the
      average JIF was quite similar with external research funds. It was found that the
      number of e-journal articles used had a strong positive correlation (Pearson's
      correlation coefficients of r > 0.9, p < 0.05) with the number of articles
      published in SCI(E) journals and the times cited regardless of the author type,
      NA handling method or time period. We also observed that the top-five
      institutions in South Korea, with respect to the number of publications in SCI(E)
      journals, were generally across a balanced range of academic activities, while
      producing significant research output and using published material. Finally, we
      confirmed that the association of e-journal use with the two quantitative
      research indicators is strongly positive, even for the analyses by field, with
      the exception of the Arts and Humanities.

PMID- 25995528
TI  - The Production of Passives by Children with Specific Language Impairment
      Acquiring English or Cantonese.
AB  - The production of passive sentences by children with specific language impairment
      (SLI) was studied in two languages, English and Cantonese. In both languages, the
      word order required for passive sentences differs from the word order used for
      active sentences. However, English and Cantonese passive sentences are quite
      different in other respects. We found that English-speaking children with SLI
      were less proficient than both same-age and younger typically developing peers in
      the use of passives, though difficulty could not be attributed to word order or a
      reliance on active sentences. Cantonese-speaking children with SLI proved less
      capable than same-age peers but at least as proficient as younger peers in their
      use of passive sentences. The implications of these cross-linguistic differences
      are discussed.

PMID- 25995529
TI  - Noun Case Suffix Use by Children with Specific Language Impairment: An
      Examination of Finnish.
AB  - Finnish-speaking children with specific language impairment (SLI, N = 15, M age =
      5;2), a group of same-age typically developing peers (TD-A, N = 15, M age = 5;2)
      and a group of younger typically developing children (TD-Y, N = 15, M age = 3;8)
      were compared in their use of accusative, partitive, and genitive case noun
      suffixes. The children with SLI were less accurate than both groups of TD
      children in case marking, suggesting that their difficulties with agreement
      extend to grammatical case. However, these children were also less accurate in
      making the phonological changes in the stem needed for suffixation. This second
      type of error suggests that problems in morphophonology may constitute a separate
      problem in Finnish SLI.

PMID- 25995530
TI  - Case Marking in Hungarian Children with Specific Language Impairment.
AB  - This study examines whether children with specific language impairment (SLI)
      acquiring a language with a rich case marking system (Hungarian) have difficulty
      with case, and, if so, whether the difficulty is comparable for spatial and
      nonspatial meanings. Data were drawn from narrative samples and from a sentence
      repetition task. Suffixes were tested both in their spatial and nonspatial
      meanings. Participants with SLI were compared to same-age peers and younger
      typically developing children matched on receptive vocabulary scores ( VC
      children ). Results show that although case-marking errors are very rare in
      spontaneous speech in Hungarian children with SLI, the number of case marked
      nouns and of different case markers is significantly lower in children with SLI.
      In the elicited production task, overall performance of the children with SLI was
      significantly below that of VC children, but children with SLI and VC children
      scored higher with spatial than with nonspatial meanings. The results are in line
      with expectations based on processing accounts which posit greater difficulties
      with less transparent details of grammar.

PMID- 25995531
TI  - Optimization of physiological parameter for macroscopic modeling of reacted
      singlet oxygen concentration in an in-vivo model.
AB  - Singlet oxygen (1O2) is generally believed to be the major cytotoxic agent during
      photodynamic therapy (PDT), and the reaction between 1O2 and tumor cells define
      the treatment efficacy. From a complete set of the macroscopic kinetic equations
      which describe the photochemical processes of PDT, we can express the reacted 1O2
      concentration, [1O2]rx, in a form related to time integration of the product of
      1O2 quantum yield and the PDT dose rate. The production of [1O2]rx involves
      physiological and photophysical parameters which need to be determined explicitly
      for the photosensitizer of interest. Once these parameters are determined, we
      expect the computed [1O2]rx to be an explicit dosimetric indicator for clinical
      PDT. Incorporating the diffusion equation governing the light transport in turbid
      medium, the spatially and temporally-resolved [1O2]rx described by the
      macroscopic kinetic equations can be numerically calculated. A sudden drop of the
      calculated [1O2]rx along with the distance following the decrease of light
      fluence rate is observed. This suggests that a possible correlation between
      [1O2]rx and necrosis boundary may occur in the tumor subject to PDT irradiation.
      In this study, we have theoretically examined the sensitivity of the
      physiological parameter from two clinical related conditions: (1) collimated
      light source on semi-infinite turbid medium and (2) linear light source in turbid
      medium. In order to accurately determine the parameter in a clinical relevant
      environment, the results of the computed [1O2]rx are expected to be used to fit
      the experimentally-measured necrosis data obtained from an in vivo animal model.

PMID- 25995532
TI  - Pre-clinic study of uniformity of light blanket for intraoperative photodynamic
      therapy.
AB  - A large-size blanket composed of the parallel catheters and silica core side
      glowing fiber is designed to substitute the hand-held point source in the
      photodynamic therapy treatment (PDT) of the malignant pleural or intraperitoneal
      diseases. It produces a reasonably uniform field for effective light coverage and
      is flexible to conform to anatomic structures in intraoperative PDT. The size of
      the blanket is 30cm*20cm. The light blanket composed of several PVC layers and a
      series of parallel catheters attached on both sides of the intralipid layer of
      0.2% concentration. On one side of the intralipid layer, the parallel fiber
      catheters were attached using thermal sealing technique. On the other side, the
      parallel detect catheters were attached along the perpendicular direction. 0.1mm
      aluminum foil was used to construct the reflection layer to enhance the
      efficiency of light delivery. The long single side-glowing fiber goes through the
      fiber catheters according to the specific fiber pattern design. Compared with the
      prototype of the first generation, the new design is more cost-efficient and more
      applicable for clinical applications. The light distribution of the blanket was
      characterized by scanning experiments which were performed in flatness and on the
      curved surface of tissue body phantom. The fluence rate generated by the blanket
      can meet requirements for the light delivery in pleural or intraperitoneal (IP)
      PDT. Taking the advantage of large coverage and flexible conformity, it has great
      value to increase the reliability and consistency of PDT.

PMID- 25995533
TI  - A heterogeneous optimization algorithm for reacted singlet oxygen for
      interstitial PDT.
AB  - Singlet oxygen (1O2) is the major cytotoxic agent for type II photodynamic
      therapy (PDT). The production of 1O2 involves the complex reactions among light,
      oxygen molecule, and photosensitizer. From universal macroscopic kinetic
      equations which describe the photochemical processes of PDT, the reacted 1O2
      concentration, [1O2]rx, with cell target can be expressed in a form related to
      time integration of the product of 1O2 quantum yield and the PDT dose rate. The
      object of this study is to develop optimization procedures that account for the
      optical heterogeneity of the patient prostate, the tissue photosensitizer
      concentrations, and tissue oxygenation, thereby enable delivery of uniform
      reacted singlet oxygen to the gland. We use the heterogeneous optical properties
      measured for a patient prostate to calculate a light fluence kernel. Several
      methods are used to optimize the positions and intensities of CDFs. The Cimmino
      feasibility algorithm, which is fast, linear, and always converges reliably, is
      applied as a search tool to optimize the weights of the light sources at each
      step of the iterative selection. Maximum and minimum dose limits chosen for
      sample points in the prostate constrain the solution for the intensities of the
      linear light sources. The study shows that optimization of individual light
      source positions and intensities is feasible for the heterogeneous prostate
      during PDT. To study how different photosensitizer distributions as well as
      tissue oxygenation in the prostate affect optimization, comparisons of light
      fluence rate were made with measured distribution of photosensitizer in prostate
      under different tissue oxygenation conditions.

PMID- 25995534
TI  - Seasonal change in the wetting characteristics of the cuticle of the Collembola
      Cryptopygus clavatus (Schott, 1893).
AB  - The littoral Collembola Cryptopygus clavatus spends the summer submerged, grazing
      on algae under water, and the winter on dry land. The cuticles of Collembola are,
      in general, highly water repellent, often superhydrophobic; the cuticle of C.
      clavatus has, in contrast, been described as not water repellent. Wetting
      properties are closely tied to surface structuring, and previous studies of
      Collembola cuticles have used the pattern of cuticular granules to explain the
      superhydrophobic properties of these cuticles. The wetting properties of the
      cuticles of C. clavatus were measured on animals acclimated to summer and winter.
      A significant difference in wetting performance was observed. Animals acclimated
      to winter conditions showed superhydrophobic non-wetting properties. Animals
      acclimated to summer conditions were not superhydrophobic, water droplets readily
      adhered to their cuticles. This large change in wetting behavior of the cuticle
      could not be explained by changes in the cuticular surface structure, which were
      very limited. Instead, we suggest a change in the epicuticular wax layer could
      explain the differences.

PMID- 25995535
TI  - Morphological and anatomical changes related to leg anomalies in Tegenaria
      atrica.
AB  - A range of leg anomalies was detected in embryos of the Tegenaria atrica spiders
      exposed to alternating temperatures of 14 and 32  degrees C. Multiple anomalies
      were observed in 13 individuals. This study is based on five individuals: two
      individuals affected by oligomely combined, respectively, with heterosymely and
      polymely, one affected by polymely with heterosymely, one by complicated polymely
      (accompanied by the reduction in length and malformations of the distal parts of
      the legs), and one individual with pure polymely. Changes in the central nervous
      system of these five individuals were described in detail on the basis of
      histological sections. The changes were mainly related to the number of
      neuromeres. Individuals affected by polymely had additional ganglia corresponding
      to the number of additional appendages, whereas the absence of a leg (oligomely)
      was associated with the absence of a ganglion. Histological analysis showed the
      fusion of ganglia in the three polymelic specimens, even though additional
      appendages were not fused.

PMID- 25995536
TI  - Histological, histochemical and ultrastructural analysis reveals functional
      division of the oesophagogastric segment in freshwater tubenose goby
      Proterorhinus semilunaris Heckel, 1837.
AB  - Histological and histochemical features of the oesophagogastric segment of the
      alimentary canal as well as ultrastructure of gastric gland cells of freshwater
      tubenose goby Proterorhinus semilunaris were examined. The studies revealed that
      despite the lack of anatomical distinction, the oesophagogastric segment is
      histologically divided into the oesophagus, oesogaster and stomach, which
      provides evidence for the functional compartmentation of this organ. The
      oesophagus was characterised by the presence of numerous goblet cells secreting
      mainly a mixture of neutral and acid mucopolysaccharides. In the stomach, the
      apical zone of the surface epithelial cells contained neutral
      mucopolysaccharides. Numerous proliferating cells were scattered throughout the
      surface epithelium. In the lamina propria of the stomach, a well-developed layer
      of gastric glands was observed. The glands were of the alveolar type and occupied
      nearly the entire length of the stomach except the pyloric region. The gastric
      gland cells were varied into light and dark; however, their ultrastructure was
      identical. All cells had numerous mitochondria and a well-developed
      tubulovesicular system typical for the oxynticopeptic cells, but pepsinogen
      granules were not present in the cytoplasm of these cells. These findings
      contribute new evidence to literature reports that not all gobiid fish are
      stomachless. Moreover, they suggest higher adaptation of the species to utilise
      protein-rich food compared to stomachless fish, and its ability to adjust the
      alimentary canal quickly to changing diet. How this may facilitate establishment
      of P. semilunaris in invaded environments remains an open question.

PMID- 25995537
TI  - Effects of stabilization exercises with a Swiss ball on neck-shoulder pain and
      mobility of adults with prolonged exposure to VDTs.
AB  - [Purpose] This study compared the effects on neck-shoulder pain and mobility of
      strengthening exercises for the neck flexors and scapular retractors performed on
      a Swiss ball and a mat. [Subjects] Twenty student volunteers were the subjects.
      [Methods] The students were randomly assigned to two groups: Mat group (n=10),
      and Swiss ball group (n=10). At pre-test, post-test, and 1-week follow-up pain
      was assessed using the visual analogue scale (VAS), the pain pressure threshold
      (PPT) of the shoulder was measured with an algometer, and neck mobility was
      measured with a Zebris. [Results] The data analysis revealed that there was a
      significant decrease in pain and significant increase in neck flexion in both
      groups, and the Swiss ball group showed better results. [Conclusion]
      Strengthening the neck flexors and scapular retractors for stabilization of the
      neck using exercises on a Swiss ball was more effective at reducing the pain and
      stabilizing the neck than mat exercises. 

PMID- 25995538
TI  - Relationship between the ability to perform the sit-to-stand movement and the
      maximum pelvic anteversion and retroversion angles in patients with stroke.
AB  - [Purpose] The purpose of this study was to investigate the relationship between
      the ability to perform the sit-to-stand movement and the maximum pelvic
      anteversion and retroversion angles of patients. [Subjects] Thirty-two stroke
      patients (66.7+/-7.6 years) (>3 months post-stroke) who were able to sit
      unsupported and 50 age-matched healthy subjects participated in this study. The
      stroke patients were classified into two groups according to the sit-to-stand
      movement test: the group that was able to stand up (the stand-able group) (18
      persons) and the group that was unable to stand up (the stand-unable group) (14
      persons). [Methods] Pelvic anteversion and retroversion maximum angles were
      measured by a manual goniometer attached to an inclinometer. [Results] The
      maximum pelvic anteversion angles were -1.6 +/- 5.0 degrees , 1.2 +/- 2.8 degrees
      , and -12.4 +/- 6.1 degrees  in the control group, the stand-able stroke group,
      and the stand-unable stroke group, respectively. A significant main effect of
      group was found. An angle discriminating between the two stroke groups was found:
      the maximum anteversion angles in the stand-able group were distributed above -5
      degrees . [Conclusion] The maximum pelvic anteversion angle was significantly
      smaller in the stand-unable group than in the stand-able and control groups. 

PMID- 25995539
TI  - Effect of exercise performance by elderly women on balance ability and muscle
      function.
AB  - [Purpose] The aim of this study was to investigate the effect of an exercise
      intervention on the balance ability and muscle function of elderly women.
      [Subjects] The subjects were randomly divided into a control group (n=10) and an
      exercise group (n=10). [Methods] The subjects participated in an elastic band
      exercise program lasting for 8 weeks, exercising for 40 minutes, four days a week
      with resting terms of 60 sec. Subjects used a band corresponding to 60% of the
      strength of the color band with which repetitive exercise was possible up to
      twelve times. The subjects performed elastic band exercises, with variations to
      the number of band exercises according to the improvement of their physical
      fitness levels. When fifteen repetitive elastic band exercises could be performed
      with no damage of the body, we changed the band for one which was one level up
      from the former one and subjects used the same band for the upper body and lower
      body. [Results] Leg muscular strength measured as sit-stand repetitions in 30 s
      significantly increased in the exercise group after the intervention compared to
      before the intervention. Leg muscular endurance measured as the number of knee
      ups in 2 minutes significantly increased in the exercise group after the
      intervention compared to before the intervention. Balance measured by one-leg
      standing time with the eyes open significantly improved in the exercise group
      after the intervention compared to before the intervention. [Conclusion] Balance
      ability and muscle function significantly improved in the exercise group and
      showing that the intervention is effective at improving balance, muscle strength,
      and muscle endurance of elderly women. 

PMID- 25995540
TI  - Splinting is effective for night-only symptomatic carpal tunnel syndrome
      patients.
AB  - [Purpose] Carpal tunnel syndrome is the most common entrapment neuropathy of the
      median nerve. Splinting is one of the most used conservative treatment methods
      for carpal tunnel syndrome. The aim of this study was to show the effectiveness
      of splinting in carpal tunnel syndrome patients who were divided into two groups
      according to their level of symptoms. [Subjects and Methods] A total of 40 carpal
      tunnel syndrome patients were divided into 2 groups based on having symptoms only
      at night or during the day were included in this study. These two groups were
      compared at the end of a 3-months splinting therapy in terms of improvement of
      severity of symptoms, functional capacity, pain level, and electrophysiological
      findings. [Results] Pain levels of both groups were similar at baseline. After
      splinting, pain levels of night-only symptomatic patients were lower than those
      of sustained symptomatic ones. No differences were found in symptom severity,
      functional capacity, and the electrophysiological findings in either group after
      the splinting. [Conclusion] The results of this study show that splinting alone
      may be sufficient to decrease the pain for night-only symptomatic patients.
      Combined therapy methods may be needed for sustained symptomatic patients. 

PMID- 25995541
TI  - The effect of aging on respiratory synergy.
AB  - [Purpose] The purpose of this study was to investigate the effect of aging on
      respiratory synergy, through the comparison of an elderly group and a young
      group, to help further understanding of postural control in the elderly.
      [Subjects and Methods] Ten community-dwelling elderly subjects and ten young
      subjects performed standing under two different respiratory conditions: quiet
      breathing and apnea. Center of foot pressure displacement and joint angular
      movements of the head, trunk, pelvis, hips, knees and ankles were measured.
      [Results] The results of this study showed that the elderly group had a
      respiratory synergy different from that of the young group. The elderly group in
      quiet stance used significantly more hip and pelvis movements when compensating
      for respiratory disturbance than standing with apnea, while the young group used
      significantly more whole body segments. There were no differences in angular
      displacements in the quiet stance between the elderly and the young groups.
      [Conclusion] The elderly group demonstrated a respiratory synergy pattern
      different from that of the young group. The findings indicate that aging changes
      the respiratory synergy pattern and this change is not due to decreased
      functioning of the ankle joint alone. 

PMID- 25995542
TI  - Intra-observer reliability in three-dimensional kinematic analysis of sacroiliac
      joint mobility.
AB  - [Purpose] Physical therapists, osteopathic practitioners, and chiropractors often
      perform manual tests to evaluate sacroiliac joint (SIJ) mobility. However, the
      available evidence demonstrates an absence of reliability in these tests and in
      investigations with kinematic analysis. The aim of this study was to verify the
      three-dimensional kinematic reliability in SIJ movement measurements. [Subjects]
      This cross-sectional study analyzed 24 healthy males, aged between 18 and 35
      years. [Methods] Three-dimensional kinematic analysis was performed for
      measurements of posterior superior iliac displacement and greater trochanter
      (femur) displacement during hip flexion movement in an orthostatic position. The
      distance variations were measured from a reference point in 3 blocks. The intra
      observer reliability was compared with the mean of three 3 blocks using the
      interclass correlation coefficient (ICC) and a 99% significance level. [Results]
      The measurements indicated a strong correlation among blocks: ICC = 0.94 for
      right side SIJ and ICC = 0.91 for left side SIJ. The mean displacement between
      the reference points was 7.7 mm on the right side and 8.5 mm on the left side.
      [Conclusion] Our results indicate that three-dimensional kinematic analysis can
      be used for SIJ mobility analyses. New studies should be performed for subjects
      with SIJ dysfunction to verify the effectiveness of this method. 

PMID- 25995543
TI  - Effects of neck exercises on swallowing function of patients with stroke.
AB  - [Purpose] This study examined the effects of neck exercises using PNF on the
      swallowing function of stroke patients with dysphasia. [Subjects and Methods] A
      total of 26 study subjects were selected and randomly divided into an
      experimental group of 13 subjects, who received the PNF-based short neck flexion
      exercises, and a control group of 13 subjects, who received the Shaker exercise.
      [Results] The experimental group showed statistically significant improvements in
      premature bolus loss, residue in the valleculae, laryngeal elevation, epiglottic
      closure, residue in the pyriform sinuses, and coating of the pharyngeal wall
      after swallowing, and improvements in pharyngeal transit time, and aspiration on
      both the new VFSS scale and the ASHA NOMS scale. [Conclusion] PNF-based short
      neck flexion exercises appear to be effective at improving swallowing function of
      stroke patients with dysphagia. 

PMID- 25995544
TI  - Muscle activation of drivers with hemiplegia caused by stroke while driving using
      a steering wheel or knob.
AB  - [Purpose] The aim of this study was to investigate three muscle activities of
      drivers with post-stoke hemiplegia while they were driving using a steering wheel
      or a spinner knob, and to compare them with those of non-disabled drivers.
      [Subjects and Methods] The subjects were four non-disabled drivers and five
      drivers with left hemiplegia. The subjects drove forward in a straight line for 5
      m and then turned right or left using the steering wheel or spinner knob with
      only their right hand. EMG electrodes were placed over the anterior deltoid,
      biceps and triceps brachii on the right-side. [Results] While differences in
      muscle activation between the spinner knob and the steering wheel in the control
      group were not significant, those of the experimental group were significant.
      Activation of the biceps brachii while the control group turned the vehicle to
      the right using the spinner knob was significantly lower than when using the
      steering wheel. Activation of the biceps brachii while the experimental group
      turned the vehicle to the right using the spinner knob was significantly lower
      than that of the control group. [Conclusion] The results of this study indicate
      that a spinner knob requires less activation of the main muscle than a steering
      wheel, especially in drivers who have had a stroke. The results could be used as
      basic data when driver rehabilitation specialists prescribe the spinner knob for
      patients. 

PMID- 25995545
TI  - Somatotype and body composition analysis of Korean youth soccer players according
      to playing position for sports physiotherapy research.
AB  - [Purpose] The purpose of this study was to investigate the somatotype and
      physical characteristic differences among elite youth soccer players. [Subjects
      and Methods] In the present study, we evaluated twenty-two Korean youth soccer
      players in different playing positions. The playing positions were divided into
      forward (FW), midfielder (MF), defender (DF), and goalkeeper (GK). The
      participants' lean body mass (LBM), fat free mass (FFM), fat mass (FM), and basal
      metabolic rate (BMR) were measured and their somatotype determined according to
      the Heath-Carter method. [Results] The youth soccer players had twelve
      ectomorphic, eight mesomorphic, and two central predominant types. The DFs were
      taller than, but otherwise similar in physical characteristics to the FWs and
      MFs. The GKs were taller and heavier than the other players; however, their
      somatotype components were not significantly different. LBM, FFM, and BMR were
      significantly higher in GKs than in FWs and MFs. Although LBM, FFM, and BMR
      values between GKs and DFs showed large differences, they were not statistically
      significant. [Conclusion] The present study may contribute to our understanding
      of the differences in somatotype and body composition of Korean youth soccer
      players involved in sports physiotherapy research. 

PMID- 25995546
TI  - Effect of toe-spread-out exercise on hallux valgus angle and cross-sectional area
      of abductor hallucis muscle in subjects with hallux valgus.
AB  - [Purpose] This study investigated whether the toe-spread-out exercise affects the
      hallux valgus angle, the cross-sectional area of the abductor hallucis muscle,
      and the hallux valgus angle during active abduction. [Subjects and Methods]
      Twenty-four subjects with hallux valgus were randomly assigned to orthosis and
      orthosis plus toe-spread-out exercise groups. The orthosis group wore the
      orthosis for 8 weeks, while the orthosis plus toe-spread-out group also performed
      the toe-spread-out exercise. The hallux valgus angle, the cross-sectional area of
      the abductor hallucis muscle, and the hallux valgus angle during active abduction
      were measured initially and after 8 weeks by radiography and ultrasonography.
      [Results] While there were no significant changes in the three parameters in the
      orthosis group, there were significant differences in the orthosis plus toe
      spread-out exercise group after 8 weeks. In addition there were significant
      differences in the three measures between the two groups. [Conclusion] The toe
      spread-out exercise reduces the hallux valgus angle and hallux valgus angle
      during active abduction, and increases the cross-sectional area of the abductor
      hallucis muscle. The toe-spread-out exercise is recommended for patients with
      mild to moderate hallux valgus. 

PMID- 25995547
TI  - The influence of accuracy constraints on EMG and kinetic variables during gait
      initiation.
AB  - [Purpose] This study investigated the effects of accuracy constraints (targets)
      placed on the stepping-limb heel-strike (HS) on the electromyogram (EMG) and
      ground reaction forces (GRFs) during gait initiation. [Subjects and Methods]
      Twenty healthy subjects (29.2 +/- 2.9 years) were asked to begin walking or
      stepping over a 10-cm-high obstacle at a fast speed. A 3-cm-diameter target was
      placed on the ground to dictate the position and accuracy of the stepping-limb
      HS. [Results] The results showed that the initiation velocity increase in the no
      target conditions was due to modulation of the stance- and stepping-limb GRFs and
      a corresponding increase in the tibialis anterior (TA) activities of both limbs
      before stepping-limb toe-off. This was achieved by significantly increasing the
      stepping- and stance-limb TAEMG1 (determined between the onset of movement and
      time to peak anteroposterior (A-P) GRF of the stepping- and stance- limb) for the
      no-target conditions. It seems, therefore, that TAEMG1 and the slope to stepping
      limb peak A-P GRF contributed to the intended velocity of initiation.
      [Conclusion] These data indicate that gait initiation and/or stepping over an
      obstacle may prove to be tasks by which motor control can be measured. The
      present study provides insight into the working mechanisms of the stepping and
      stance limbs and shows a clear need to further investigate whether the intact or
      affected limb should be used to initiate gait during rehabilitation and
      prosthetic training. 

PMID- 25995548
TI  - Effects of computer assisted cognitive rehabilitation on brain wave, memory and
      attention of stroke patients: a randomized control trial.
AB  - [Purpose] This study investigated brain wave, memory and attention changes in
      adult stroke patients using computer assisted cognitive rehabilitation (CACR).
      [Subjects] Twenty-five stroke patients were randomly allocated to either the CACR
      group (n=12) or the control group (n=13). [Methods] Two expert therapists
      provided the CACR group and the control group with traditional rehabilitation
      therapy in 30-minute sessions, semi-weekly, for 6 weeks. CACR was provided only
      to the CACR group. The control group received traditional rehabilitation therapy
      only. Before and after the 6 weeks of intervention, electroencephalography (EEG)
      and a computerized neurocognitive function test (CNT) were performed, and the
      results were analyzed. [Results] After the intervention, the CACR group showed
      significant differences in the frontal lobe (Fp1, Fp2, and F4) and in the
      parietal lobe (P3 and P4), and also showed significant differences in CNT memory
      (DST and VST forward/backward test) and attention (VCPT correct responses), but
      no notable changes were observed in the control group. [Conclusion] These results
      suggest that CACR is feasible and suitable for individuals with stroke. Detailed
      and diverse investigations should be performed considering the numbers and
      characteristics of subjects, and the limitations affecting the CACR training
      period. 

PMID- 25995549
TI  - Effects of the ankle angle of an ankle foot orthosis on foot pressure during the
      gait in healthy adults.
AB  - [Purpose] The purpose of this study was to investigate the effects of the ankle
      angle of an ankle foot orthosis (AFO) on foot pressure during the gait in healthy
      adults. [Subjects] Sixteen healthy males with neither orthopedic nor neurological
      problems participated in this study. [Methods] Subjects walked on a walkway at a
      self-selected pace with an AFO set at four different ankle angles (-5 degrees , 0
      degrees , 5 degrees , and 10 degrees ). Foot pressure was measured randomly
      according to the ankle angle of the AFO using an F-scan system. Three trials were
      measured and averaged for data analysis. [Results] The peak foot pressure of the
      hallux, 2nd-5th toes, 2nd and 3rd metatarsal heads, 4th and 5th metatarsal heads,
      and the heel showed significant differences among the AFO ankle angles: angles of
      0 degrees  and -5 degrees  increased the foot pressure of the lateral legions,
      and the peak foot pressure of the heel at an AFO ankle angle of 10 degrees  was
      significantly greater than those of the other angles. [Conclusion] The ankle
      angle of the AFO affected foot pressure and gait patterns during gait. The
      results suggest that the appropriate angle for an AFO is between 5 degrees  and
      10 degrees  when AFOs are prescribed by clinicians. 

PMID- 25995550
TI  - Comparison of selective electromyographic activity of the superficial lumbar
      multifidus between prone trunk extension and four-point kneeling arm and leg lift
      exercises.
AB  - [Purpose] This study examined the selective electromyographic activity of the
      lumbar paraspinal muscles in healthy male and female subjects in the prone trunk
      extension (PTE) and four-point kneeling arm and leg lift (FPKAL) exercises to
      determine the most beneficial exercise for selective activation of the lumbar
      multifidus (LM). [Subjects and Methods] Twenty healthy male and female subjects
      participated in this study. Surface electromyographic data were collected from
      the left-side lumbar erector spinae (LES) and LM muscles during PTE and FPKAL
      exercises. [Results] The LM/LES ratio related to selective activation of the
      lumbar paraspinal muscles during the FPKAL exercise was higher than that during
      PTE. [Conclusion] FPKAL exercise is safe and effective for the selective
      activation of the LM muscle. 

PMID- 25995551
TI  - Effects on ROM and joint position sense of the neck of two different
      interventions.
AB  - [Purpose] The purpose of this study was to evaluate whether neuromuscular joint
      facilitation (NJF) training is superior to NJF distal resistance training at
      improving the ROM and proprioceptive acuity of the neck. [Subjects] 10 healthy
      subjects (8 males, 2 females) participated in this study. [Methods] The
      participants were allocated to three groups: 10 in the control group, 10 in the
      NJF distal resistance training group, and 10 in the NJF training group. A
      miniature wireless motion recorder was used to record the maximum cervical range
      of motion and joint position error (JPE) before and after the interventions. The
      three interventions were tested on different days. [Results] No difference of ROM
      was observed among the three groups. A significant pre- to post-intervention
      decrease in JPE in extension was identified in the NJF group. No other
      significant differences were observed among the three groups. [Conclusion] The
      NJF training conferred remarkable benefits on the cervical JPE of healthy people.
      This result suggests that the best way to improve proprioceptive acuity is
      intervention together with proximal resistance training, such as NJF training. 

PMID- 25995552
TI  - Effect of mirror therapy with tDCS on functional recovery of the upper extremity
      of stroke patients.
AB  - [Purpose] This study aimed to determine the effect of mirror therapy (MT) with
      transcranial direct current stimulation (tDCS) on the recovery of the upper
      extremity function of chronic stroke patients. [Subjects] Twenty-seven patients
      at least 6 months after stroke onset were divided randomly into an experimental
      group (14 patients) and a control group (13 patients). [Methods] All subjects
      received tDCS for 20 min followed by a 5 min rest. Then the experimental group
      received MT while the control group conducted the same exercises as the
      experimental group using a mirror that did not show the non-paretic upper
      extremity. The groups performed the same exercises for 20 min. All subjects
      received this intervention for 45-min three times a week for 6 weeks. [Results]
      After the intervention, the experimental group showed significant improvements in
      the box and block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA),
      and a significant decrease in the Jebsen-Taylor test. The control group showed a
      significant increase in grip strength after the intervention, and a significant
      decrease in the Jebsen-Taylor test. Comparison of the result after the
      intervention revealed that the experimental group showed more significant
      increases in the BBT and grip strength than the control group. [Conclusion] These
      results show that MT with tDCS has a positive effect on the functional recovery
      of the upper extremity of stroke patients, through activating motor regions in
      the brain, and thus plays an important role in recovery of neuroplasticity. 

PMID- 25995553
TI  - Effects of special composite stretching on the swing of amateur golf players.
AB  - [Purpose] The study investigated stretching for safer a golf swing compared to
      present stretching methods for proper swings in order to examine the effects of
      stretching exercises on golf swings. [Subjects] The subjects were 20 amateur golf
      club members who were divided into two groups: an experimental group which
      performed stretching, and a control group which did not. The subjects had no bone
      deformity, muscle weakness, muscle soreness, or neurological problems. [Methods]
      A swing analyzer and a ROM measuring instrument were used as the measuring tools.
      The swing analyzer was a GS400-golf hit ball analyzer (Korea) and the ROM
      measuring instrument was a goniometer (Korea). [Results] The experimental group
      showed a statistically significant improvement in driving distance. After the
      special stretching training for golf, a statistically significant difference in
      hit-ball direction deviation after swings were found between the groups. The
      experimental group showed statistically significant decreases in hit ball
      direction deviation. After the special stretching training for golf,
      statistically significant differences in hit-ball speed were found between the
      groups. The experimental group showed significant increases in hit-ball speed.
      [Conclusion] To examine the effects of a special stretching program for golf on
      golf swing-related factors, 20 male amateur golf club members performed a 12-week
      stretching training program. After the golf stretching training, statistically
      significant differences were found between the groups in hit-ball driving
      distance, direction deviation, deflection distance, and speed. 

PMID- 25995554
TI  - Sensitivity of the accelerometer as a measurement tool for upper extremity
      movement by stroke patients: a comparison with the action research arm test.
AB  - [Purpose] This study investigated the sensitivity of an accelerometer in a
      comparison with the Action Research Arm Test (ARAT). [Subjects] Fifteen stroke
      patients participated in this study. [Methods] Subjects wore accelerometers on
      both wrists and performed the ARAT items. We then compared the data measured by
      the accelerometer with that of the ARAT. [Results] ARAT scores were higher on the
      non-affected side than the affected side, while the amount of upper extremity
      movement was higher on the affected side. The correlation coefficients for the
      two tools were not significantly different. [Conclusion] Our findings indicate
      that an accelerometer is a useful and sensitive instrument for clinically
      measuring the upper extremity activity of patients with stroke. 

PMID- 25995555
TI  - Influence of pelvic position and vibration frequency on muscle activation during
      whole body vibration in quiet standing.
AB  - [Purpose] The purpose of this study was to investigate muscle activation related
      to postural stability depending on the pelvic position and frequency of whole
      body vibration (WBV) during quiet standing, and to identify the most effective
      training conditions that elicit the highest neuromuscular responses. [Subjects
      and Methods] Eighteen healthy subjects voluntarily participated in this single
      group, repeated-measures study in which surface electromyography (EMG) data for
      the upper trapezius, rectus abdominis, external oblique abdominis, erector
      spinae, gluteus maximus, rectus femoris, semitendinosus, and medial gastrocnemius
      were collected at three frequencies (0 Hz, 10 Hz, and 20 Hz) of WBV and three
      pelvic positions (neutral, anterior tilt, posterior tilt) for each subject during
      quiet standing. [Results] The EMG activities of all the recorded muscles showed
      significant differences between the three frequencies of WBV and three pelvic
      positions during quiet standing. [Conclusion] The study findings suggest that a
      higher WBV frequency (20 Hz) should be used to strengthen most muscles, and that
      using the posterior pelvic tilt during WBV is much more effective at
      strengthening and training muscles related to core stability. 

PMID- 25995556
TI  - Effect of ankle-foot orthosis on weight bearing of chronic stroke patients
      performing various functional standing tasks.
AB  - [Purpose] This study examined how an ankle-foot orthosis (AFO) influences the
      weight-bearing of chronic stroke patients during the performance of five
      functional standing tasks. [Subjects and Methods] Sixteen patients with stroke
      participated in this experiment. The subjects performed functional standing tasks
      with or without the AFO and weight bearing was measured during the tasks.
      [Results] Patients showed increased weight-bearing ability on the affected side
      during wearing the AFO in all tasks, and there were significant differences among
      Tasks 1, 2, and 3. Patients showed a small amount of increased weight bearing on
      the unaffected side while wearing the AFO in all tasks except for Task 2.
      [Conclusion] ADL-related functional standing tasks with AFO increased the weight
      bearing. 

PMID- 25995557
TI  - Analysis of changes in pulmonary functions at rest following humidity changes.
AB  - [Purpose] The purpose of this study was to compare the effect of humidity changes
      on the values of pulmonary function at rest. [Subjects and Methods] This study
      was conducted with 30 young adults (9 males, 21 females; mean age 19.4 years).
      Participants' mean height was 165.1 cm, and their mean weight was 60.2 kg. The
      experimental setting was a laboratory in which temperature was fixed at 25 
      degrees C. Using a humidifier, relative humidity was successively to adjusted
      25%, 50%, and 90%, and pulmonary were measured functions at each level. Using a
      spirometer, forced vital capacity (FVC), forced expiratory volume in one second
      (FEV1), expiratory reserve volume (ERV), and tidal volume (TV) were measured, and
      the results were compared and analyzed. [Results] Controlling for temperature,
      FVC and FEV1 showed statistically significant differences among different levels
      of relative humidity, but FEV1/FVC, TV, and ERV showed no significant difference.
      [Conclusion] In the case of exercises that require large respiration volumes,
      such as aerobic exercises or exercise load tests, it is recommended that higher
      than normal humidity levels should be maintained. 

PMID- 25995558
TI  - Mechanical ventilation and mobilization: comparison between genders.
AB  - [Purpose] To investigate the impact of gender on mobilization and mechanical
      ventilation in hospitalized patients in an intensive care unit. [Subjects and
      Methods] A retrospective cross-sectional study was conducted of the medical
      records of 105 patients admitted to a general intensive care unit. The length of
      mechanical ventilation, length of intensive care unit stay, weaning, time to
      sitting out of bed, time to performing active exercises, and withdrawal of
      sedation exercises were evaluated in addition to the characteristics of
      individuals, reasons for admission and risk scores. [Results] Women had
      significantly lower values APACHE II scores, duration of mechanical ventilation,
      time to withdrawal of sedation and time to onset of active exercises.
      [Conclusion] Women have a better functional response when admitted to the
      intensive care unit, spending less time ventilated and performing active
      exercises earlier. 

PMID- 25995559
TI  - Reliability and validity of the closed kinetic chain upper extremity stability
      test.
AB  - [Purpose] The purpose of this study was to examine the reliability and validity
      of the Closed Kinetic Chain Upper Extremity Stability (CKCUES) test. [Subjects
      and Methods] A sample of 40 subjects (20 males, 20 females) with and without pain
      in the upper limbs was recruited. The subjects were tested twice, three days
      apart to assess the reliability of the CKCUES test. The CKCUES test was performed
      four times, and the average was calculated using the data of the last 3 tests. In
      order to test the validity of the CKCUES test, peak torque of internal/external
      shoulder rotation was measured using an isokinetic dynamometer, and maximum grip
      strength was measured using a hand dynamometer, and their Pearson correlation
      coefficients with the average values of the CKCUES test were calculated.
      [Results] The reliability of the CKCUES test was very high (ICC=0.97). The
      correlations between the CKCUES test and maximum grip strength (r=0.78-0.79), and
      the peak torque of internal/external shoulder rotation (r=0.87-0.94) were high
      indicating its validity. [Conclusion] The reliability and validity of the CKCUES
      test were high. The CKCUES test is expected to be used for clinical tests on
      upper limb stability at low price. 

PMID- 25995560
TI  - Effects of mental practice on stroke patients' upper extremity function and daily
      activity performance.
AB  - [Purpose] The purpose of this study was to evaluate the effects of mental
      practice on stroke patients' upper extremity function and activities of daily
      living (ADL). [Subjects and Methods] In this study, 29 stroke patients were
      randomly assigned to two groups: an experimental group (n=14) and a control group
      (n=15). The experimental group performed 10 minutes of mental practice once a
      day, 5 days a week for 2 weeks in combination with conventional rehabilitation
      therapy. For the control group, general rehabilitation therapy was provided
      during the same sessions as the experimental group. The Action Research Arm Test
      (ARAT) and the Fugl-Myer assessment (FMA) were used to measure upper extremity
      function, and the Modified Bathel Index (MBI) was used to measure daily activity
      performance. [Results] After the intervention, the mental practice group showed
      significant improvements in upper extremity function on the affected side and ADL
      scores compared to the control group. [Conclusion] The results of this study
      demonstrate mental practice intervention is effective at improving stroke
      patients' upper extremity function and daily activity performance. In follow-up
      studies, securing a greater number of experimental subjects, and evaluation of
      the intervention's therapeutic durability are required. 

PMID- 25995561
TI  - Effects of activation of the foot on trunk mobility of patients with hemiplegia.
AB  - [Purpose] The purpose of this study was to determine the effects of activation of
      the foot on the trunk mobility of patients with hemiplegia. [Subjects] Sixteen
      subjects with hemiplegia took part in the immediate group (IG), and 14 subjects
      with hemiplegia participated in the 2-month group (2MG). [Methods] The subjects
      in IG were given one leg stance training through activation of the foot only
      once, and 2MG received the same intervention for 30 minutes 3 times a week for, 8
      weeks. The Spinal Mouse was used to collect spinal alignment data. Also, the
      trunk Impairment Scale (TIS) and Sensory test were used as functional tests.
      [Results] Sacral hip (SH), lumbar spine (LS) and thoracic spine (TS) angles in IG
      improved significantly, but not inclination (I), and 2MG showed increased angles
      of SH, LS and I, but not TS. Also, TIS Dynamic, TIS Coordination and Sensory test
      results of 2MG increased significantly. [Conclusion] One leg stance training
      through activation of the foot was effective at improving sensory input and
      alignment of the spine, therefore trunk mobility was improved. 

PMID- 25995562
TI  - Aerobic interval exercise with an eccentric contraction induces muscular
      hypertrophy and augmentation of muscular strength in rats.
AB  - [Purpose] The purpose of this study was to examine whether an aerobic interval
      exercise using an eccentric contraction would result in skeletal muscular
      hypertrophy and augmentation of muscular strength in rats. [Subjects and Methods]
      Twenty-one female Wistar rats were used in this study. The rats were randomly
      divided into three groups. The control group performed no exercise. The aerobic
      endurance exercise group ran for 90 min. The aerobic interval exercise group ran
      for a total of 90 minutes in 5 minute bouts separated by 2 minute rest periods.
      The exercise groups ran on a downhill treadmill incline, once every three days,
      for a total of twenty sessions. [Results] The muscle wet weights, the muscle
      fiber cross-section minor axes, and the tetanus tension results of the aerobic
      endurance and aerobic interval exercise groups were significantly larger than
      those of the control group. [Conclusion] These results indicate that aerobic
      interval exercise may be an effective method of inducing hypertrophy and
      augmenting muscular strength in skeletal muscle. 

PMID- 25995563
TI  - Factors affecting the coefficient of variation of stride time of the elderly
      without falling history: a prospective study.
AB  - [Purpose] The purpose of this study was to investigate the factors affecting the
      coefficient of variation (CV) of stride time in an exercise intervention for the
      elderly without falling history. [Subjects and Methods] The subjects were 42
      elderly women who had participated in a care prevention program for 12 weeks.
      Stride time CV, motor function, movement ability, balance, Modified Falls
      Efficacy Scale (MFES) score, and Life-space Assessment (LSA) score before and
      after the intervention were examined for significant differences using the paired
      t-test. Multiple regression analysis was used to determine the factors that
      changed in the stride time CV. [Results] There were significant differences in
      muscle strength, sit-and-reach flexibility, the one-leg standing time (eyes
      open), the maximum walking speed, local stability of trunk acceleration, The
      Timed Up and Go Test (TUG-T), the MFES score, and the LSA score between the pre
      intervention and post-intervention. Stepwise multiple regression analysis
      revealed that improvement of quadriceps muscle strength, sit-and-reach
      flexibility, the one-leg standing time, TUG-T, local stability of trunk
      acceleration (vertical direction) and MFES score were independent variables
      explaining the reduction in stride time CV. [Conclusion] The results was
      suggested that it might be possible to reduce the stride time CV by improving
      strength, flexibility and dynamic balance, and reducing fear of falls through
      interventions. 

PMID- 25995564
TI  - Effect of spatial target reaching training based on visual biofeedback on the
      upper extremity function of hemiplegic stroke patients.
AB  - [Purpose] The aim of this study was to determine the effect of spatial target
      reaching training (TRT) based on visual biofeedback (VB) on the upper extremity
      (UE) function of hemiplegic subjects. [Subjects and Methods] Forty subjects
      between six and eighteen months post-stroke were enrolled in this study. They
      were randomly allocated to an experimental group (EG, n=20) and a control group
      (CG, n=20). All subjects received an hour of routine therapy for stroke three
      times a week for four weeks. Subjects in EG received additional spatial TRT based
      on VB using a 2-dimensional motion capture analysis system. Both groups were
      tested at pre and post-intervention. The motor function of each subject's UE was
      assessed using the Fugl-Meyer (FM) test of UE and the Wolf Motor Function Test
      (WMFT). The reaching speed, angle and maximum reach distance were recorded using
      the motion capture analysis system. The experimental data were analyzed using the
      paired and independent t-tests. [Results] The mean change scores of the FM Test
      of UE and WMFT show there was significantly more improvement at post-intervention
      in EG than in CG. Also, the speed and angle reached showed significantly more
      increase in the EG compared with the CG. [Conclusions] The findings indicate that
      UE motor recovery of hemiplegic stroke patients can be enhanced through the use
      of TRT based on VB. 

PMID- 25995565
TI  - Factors affecting symptoms and functionality of patients with carpal tunnel
      syndrome: a retrospective study.
AB  - [Purpose] The aim of this retrospective study was to determine the associations
      between clinical, physical, and neurophysiological outcomes and self-reported
      symptoms and functions of patients after surgical carpal tunnel release.
      [Subjects and Methods] Among 261 patients who had undergone open surgical carpal
      tunnel release within the last three years, 83 (mean age 50.27 +/- 11.13 years)
      participated in this study. Their socio-demographics and comorbidities were
      recorded. The intensity of pain, paresthesia, and fatigue symptoms in the hand
      were assessed by means of a Visual Analogue Scale, the Semmes-Weinstein
      Monofilaments test of light touch pressure sensation, and Jamar dynamometry for
      measurement of grip and pinch strengths. The Boston Carpal Tunnel Questionnaire
      evaluated the severity of symptoms and hand functional status, and the variables
      were analyzed by multivariate linear regression. [Results] The severity of the
      symptoms and functional status of release surgery patients was associated with
      diabetes mellitus, migraine, night pain, paresthesia and fatigue symptoms,
      impaired light touch pressure, and lack of medical treatment. [Conclusion]
      Appropriate post-surgery treatment programs for these factors should be taken
      into consideration to help patients obtain optimal functionality and health in
      their daily lives. 

PMID- 25995566
TI  - Assessment of spine pain presence in children and young persons studying in
      ballet schools.
AB  - [Purpose] Spine disorders affect various sections of the spine and have a variety
      of causes. Most pain occurs in the lumbo-sacral and cervical regions. Dance is
      associated with exercise. High levels of physical activity predispose to back
      pain occurrence. [Subjects and Methods] The subjects were 237 ballet learners; 80
      children (primary school level), mean age 11.24+/-0.77, mean of years of training
      ballet 2.14+/-0.74; 93 students (junior high school level), mean age 14.01+/
      0.84, mean of years of learning ballet 4.64+/-1.24; 64 students (high school)
      mean age 17.01+/-0.77, mean of years of learning ballet 7.47+/-1.54. Numeric
      rating scale was used to determine spine pain. [Results] Feelings of pain were
      analyzed on the basis of "now" and "before" between levels education by using
      point statistics and statistical tests to compare groups. "Now" exhibited weaker
      back pain feelings than "before" at all the education levels. There were
      statistically significant differences in pain feeling for "before" (at any time
      of learning) and "now" (the day of survey). [Conclusion] All patients reported
      pain "before" and "now" in cervical, thoracic and lumbar spine. At all levels of
      education there were statistically significant differences in feelings of pain
      between "before" and "now". 

PMID- 25995567
TI  - Work-related musculoskeletal disorders among dental professionals in Saudi
      Arabia.
AB  - [Purpose] Musculoskeletal disorders are common causes of work-related disability
      in different professions involving the frequent practice of lifting, stooping,
      twisting, prolonged sitting, or standing. The dental profession is one such
      profession. Our aim was to determine the prevalence of work-related
      musculoskeletal disorders among dental professionals in Saudi Arabia, the factors
      associated with them, and their consequences and to propose preventive measures
      for them. [Subjects and Methods] A self-administered online questionnaire was
      sent to 225 members of the Saudi Dental Association. It included questions on
      demographic and professional characteristics, general medical history, and
      history of work-related musculoskeletal disorders before and after joining the
      dental profession. [Results] The questionnaire was completed by 65% of the
      respondents. Among them 85% reported that they had developed some pain due to
      work after joining the dental profession, and 42% reported that they were
      suffering pain at the time of the survey. Besides lower back, shoulder, and neck
      regions, the hands, upper back, and other regions like the elbows, buttocks,
      thighs, leg, and feet were areas in which they pain. [Conclusion] The prevalence
      of work-related musculoskeletal disorders among dental professionals in Saudi
      Arabia is high, affecting their daily activities, sometimes even forcing them to
      change their work setting. Age, gender, specialty of work, work setting, number
      of contact hours with patients, etc., were all found to be related to their work
      related pain. We need to emphasize the role of ergonomics, counseling, proper
      techniques of patient handling, etc., during the training of dental professionals
      so that they can work efficiently. 

PMID- 25995568
TI  - Does proprioceptive system stimulation improve sit-to-walk performance in healthy
      young adults?
AB  - [Purpose] Sit-to-walk performance is linked to proper proprioceptive information
      processing. Therefore, it is believed that an increase of proprioceptive inflow
      (using muscle vibration) might improve sit-to-walk performance. However, before
      testing muscle vibration effects on a frail population, assessment of its effects
      on healthy young people is necessary. Thus, the aim of this study was to
      investigate the effects of muscle vibration on sit-to-walk performance in healthy
      young adults. [Subjects and Methods] Fifteen young adults performed the sit-to
      walk task under three conditions: without vibration, with vibration applied
      before movement onset, and with vibration applied during the movement. Vibration
      was applied bilaterally for 30 s to the tibialis anterior, rectus femoris, and
      upper trapezius muscles bellies. The vibration parameters were as follows: 120 Hz
      and 1.2 mm. Kinematics and kinetic data were assessed using a 3D motion capture
      system and two force plates. The coordinates of reflective markers were used to
      define the center-of-mass velocities and displacements. In addition, the first
      step spatiotemporal variables were assessed. [Results] No vibration effect was
      observed on any dependent variables. [Conclusion] The results show that
      stimulation of the proprioceptive system with local muscle vibration does not
      improve sit-to-walk performance in healthy young adults. 

PMID- 25995570
TI  - The effects of chest expansion resistance exercise on chest expansion and maximal
      respiratory pressure in elderly with inspiratory muscle weakness.
AB  - [Purpose] The aim of this study was to examine the effect of chest expansion
      resistance exercises (CERE) on chest expansion, maximal inspiratory pressure
      (MIP), and maximal expiratory pressure (MEP) in elderly people with inspiratory
      muscle weakness. [Subjects] Thirty elderly people with inspiratory muscle
      weakness (MIP < 80% of the predicted value) were randomly and equally assigned to
      a chest expansion resistance exercise (CERE) group, core conditioning exercise
      (CCE) group, and control group. [Methods] The intervention was applied to the
      CERE group and CCE group five times per week, 30 minutes each time, for six
      weeks. A tapeline was used to measure upper and lower chest expansion. MIP and
      MEP before and after the intervention were measured and compared. [Results] There
      was significant improvement in upper and lower chest expansion and MIP after the
      intervention in both the CERE group and the CCE group, whereas the control group
      did not show any significant difference. MEP did not significantly change in any
      of the three groups after the intervention. [Conclusion] The CERE group underwent
      greater changes than the CCE group, which proves that the CERE is more effective
      for improving elderly people's chest expansion capacity and MIP in elderly
      people. Therefore, application of the CERE by therapists is recommended if the
      environment and conditions are appropriate for enhancement of chest expansion
      capacity and MIP in elderly people. 

PMID- 25995569
TI  - Blood levels related to the Z-score of bone mineral density in young males and
      females.
AB  - [Purpose] The purpose of this study was to investigate the blood levels related
      to the bone mineral density by using the dual energy X-ray absorption for females
      before menopause and males younger than 50 years old. [Subjects and Methods]
      Between August 1, and September 15, 2013, the Z-score was measured in females
      before menopause and males younger than 50 years old using a bone mineral density
      measuring instrument. After the measurement, the subjects were classified into
      two groups, that is, the below expectations and within expectations groups. Next,
      we analyzed and compared the differences in age, body mass index, and blood
      levels between the 2 groups. [Results] The results showed a correlation of 0.212
      for total protein, -0.317 for alanine aminotransferase, -0.199 for gamma-glutamyl
      transferase, -0.358 for alkaline phosphatase, 0.266 for uric acid, -0.313 for
      lactate dehydrogenase, 0.244 for creatinine, -0.234 for the red blood cell count,
      and -0.230 for the red cell distribution width in patients with less than
      expected level for their age. [Conclusion] In conclusion, osteoporosis may occur
      in females before menopause and males younger than 50 years old, and aggressive
      attention is required for prevention and treatment. 

PMID- 25995571
TI  - The effects of horse-riding simulator exercise and Kendall exercise on the
      forward head posture.
AB  - [Purpose] The aim of this study was to examine the effects of horse-riding
      simulator exercise and Kendall exercise on forward head posture. [Subjects and
      Methods] Thirty elderly college students with a forward head posture were
      randomly divided into two groups for 15 persons each, a horse-riding simulator
      group and Kendall exercise group, and performed exercise for eight weeks.
      [Results] The horse-riding simulator group and Kendall exercise group showed
      significant differences after the intervention in New York state posture rating,
      craniovertebral angle, and cranial rotation angle. The horse-riding simulator
      group showed a significantly smaller value than the Kendall exercise group for
      New York state posture rating evaluation after the intervention. [Conclusion] The
      results of this study indicate that horse-riding simulator exercise is more
      effective on forward head posture than Kendall exercise. Therefore, horse-riding
      simulator exercise can be used as a new simple treatment method for the ever
      growing forward head posture. 

PMID- 25995572
TI  - Effect of revised high-heeled shoes on foot pressure and static balance during
      standing.
AB  - [Purpose] The purpose of this study was to investigate the effects of revised
      high-heeled shoes on the foot pressure ratio and static balance during standing.
      [Subjects and Methods] A single-subject design was used, 15 healthy women wearing
      revised high-heeled shoes and general high-heeled shoes in a random order. The
      foot pressure ratio and static balance scores during standing were measured using
      a SpaceBalance 3D system. [Results] Forefoot and rearfoot pressures were
      significantly different between the 2 types of high-heeled shoes. Under the 3
      conditions tested, the static balance score was higher for the revised high
      heeled shoes than for the general high-heeled shoes, but this difference was not
      statistically significant. [Conclusion] Revised high-heeled shoes are preferable
      to general high-heeled shoes, as they result in normalization of normalized foot
      pressure and a positive effect on static balance. 

PMID- 25995573
TI  - Does whole-body vibration training in the horizontal direction have effects on
      motor function and balance of chronic stroke survivors? A preliminary study.
AB  - [Purpose] The objective of this study was to investigate the effects of whole
      body vibration (WBV) in the horizontal direction on the motor function and
      balance of chronic stroke survivors. [Subjects and Methods] This study was a
      randomized controlled trial. Twenty-one individuals with chronic stroke from an
      inpatient rehabilitation center participated in the study. The participants were
      allocated to either the WBV training group or the control group. The WBV training
      group (n = 12) received whole-body vibration delivered in the horizontal
      direction (15 min/day, 3 times/week, 6 wks) followed by conventional
      rehabilitation (30 min/day, 5 times/week, 6 wks); the control group (n = 9)
      received conventional rehabilitation only (30 min/day, 5 times/week, 6 wks).
      Motor function was measured by using the Fugl-Meyer assessment, and balance was
      measured by using the Berg Balance Scale (BBS) and the Timed Up and Go (TUG) test
      before and after the interventions. [Results] After the interventions, all
      variables improved significantly compared with the baseline values in the WBV
      training group. In the control group, no significant improvements in any
      variables were noted. In addition, the BBS score in the WBV training group
      increased significantly compared with that in the control group. [Conclusion] WBV
      training with whole-body vibration delivered in the horizontal direction may be a
      potential intervention for improvement of motor function and balance in patients
      who previously experienced a stroke. 

PMID- 25995574
TI  - Association between mean platelet volume and bone mineral density in patients
      with ankylosing spondylitis and diagnostic value of diffusion-weighted magnetic
      resonance imaging.
AB  - [Purpose] The aim this study was to assess the relation between bone mineral
      density (BMD) and mean platelet volume (MPV) in ankylosing spondylitis (AS)
      patients, and evaluate the diagnostic role of the diffusion-weighted magnetic
      resonance imaging (MRI). [Subjects and Methods] Fifty patients diagnosed with AS
      were divided into two groups on the basis of BMD, a normal group (n=30) and an
      osteopenic (n=20) group. [Results] Duration of disease in the group with a normal
      BMD was 10.3+/-7.0 years, while it was 16.7+/-12.2 years in the osteopenia group.
      MPV was high in the osteopenia group, while no significant differences were
      observed between the groups in terms of apparent diffusion coefficient (ADC) and
      platelet distribution width (PDW). There was a positive correlation between MPV
      and duration of disease. Correlations between ADC value and the lumbar T score,
      femoral neck T score, and duration of disease were insignificant. A negative
      correlation was observed between BMD and disease duration. [Conclusion] Diffusion
      weighted imaging provides valuable results in osteoporosis but is not a suitable
      technique for evaluating BMD in patients with AS because of the local and
      systemic inflammatory effects in the musculoskeletal system. The common
      pathophysiology of atherosclerosis and osteoporosis plays an important role in
      the negative correlation observed between MPV and BMD in patients with AS. 

PMID- 25995575
TI  - Intra- and inter-examiner reliability of goniometer and inclinometer use in
      Craig's test.
AB  - [Purpose] The purpose of this study was to determine the inter- and intra
      examiner reliability of measurement methods for femoral anterversion during
      Craig's test. [Subjects and Methods] The study included 37 healthy participants
      (20 males and 17 females). Two novice examiners (Department of Physical Therapy
      students at Silla University) used three different methods to measure the femoral
      anterversion during Craig's test: a goniometer, a goniometer with a laser beam,
      and an inclinometer. [Results] The intra-examiner reliability was high for both
      examiners with all three measurement methods, with scores of 0.82, 0.86, and 0.73
      for examiner 1 and 0.74, 0.78, and 0.72 for examiner 2 for the goniometer,
      goniometer with the laser beam, and inclinometer, respectively. The inter
      examiner reliability during Craig's test was below moderate for both the
      goniometer (0.25) and inclinometer (0.27) and moderate for the goniometer with
      the laser beam (0.62). [Conclusion] This study found that Craig's test using a
      goniometer with a laser beam had high intra-examiner reliability and moderate
      inter-examiner reliability. Clinically, these findings may supplement existing
      measurement skills and reduce the difficulty of locating the goniometer axis
      during Craig's test. 

PMID- 25995576
TI  - Wii Fit balance training or progressive balance training in patients with chronic
      stroke: a randomised controlled trial.
AB  - [Purpose] The aim of this study was to compare the effects of Wii Fit balance
      training (WBT) and progressive balance training (PBT) approaches on balance
      functions, balance confidence, and activities of daily living in chronic stroke
      patients. [Subjects] A total of 30 patients were randomized into the WBT (n=15)
      and PBT (n=15) groups. [Methods] All of the subjects received exercise training
      based on a neurodevelopemental approach in addition to either Wii Fit or
      progressive balance training for total of 1 hour a day, 3 days per week for 4
      weeks. Primary measurements were static balance function measured with a Wii
      Balance Board and dynamic balance function assessed with the Berg Balance Scale,
      Timed Up and Go test, Dynamic Gait Index, and Functional Reach Test. Secondary
      measures were balance confidence assessed with the Activities-specific Balance
      Confidence scale and activities of daily living evaluated with the Frenchay
      Activity Index. [Results] There was not remarkable difference between the two
      treatments in dynamic balance functions, balance confidence, and activities of
      daily living. [Conclusion] Although both of the approaches were found to be
      effective in improving the balance functions, balance confidence, and activities
      of daily living, neither of them were more preferable than the other for the
      treatment of balance in patients with chronic stroke. 

PMID- 25995578
TI  - The effects of virtual reality game exercise on balance and gait of the elderly.
AB  - [Purpose] The aim of this study was to examine the effects of ball exercise as a
      general exercise on the balance abilities of elderly individuals by comparing
      ball exercise with virtual reality exercise. [Subjects and Methods] Thirty
      elderly individuals residing in communities were randomly divided into a virtual
      reality game group and a ball exercise group and conducted exercise for 30 min 3
      times a week for 8 weeks. [Results] Step length increased significantly, and the
      average sway speed and Timed Up and Go time significantly decreased in both
      groups. A comparison of sway length after the intervention between the two groups
      revealed that the virtual reality game exercise resulted in a reduction than the
      ball exercise. [Conclusion] The results of this study indicated that the virtual
      reality game exercise may improve balance and gait of elderly individuals in
      communities. 

PMID- 25995577
TI  - The effects of trunk stability exercise and a combined exercise program on pain,
      flexibility, and static balance in chronic low back pain patients.
AB  - [Purpose] The aim of this study was to examine the effect of trunk stability
      exercise and combined exercise program on pain, flexibility, and static balance
      in chronic low back pain patients. [Subjects and Methods] Thirty persons
      diagnosed with chronic low back pain were divided into a trunk stability exercise
      group and a combined exercise group and then conducted exercise for six weeks.
      [Results] VAS and sway lengths decreased significantly in both groups. A
      comparison of sway lengths after the intervention between the two groups revealed
      that the trunk stability exercise group had a bigger decrease than the combined
      exercise group. [Conclusion] The results of this study indicated that trunk
      stability exercise would have bigger effect than combined exercise on the daily
      activities of chronic low back pain patients as it strengthens deep abdominal
      muscles and improves flexibility and balancing ability. 

PMID- 25995579
TI  - Effect of thorax correction exercises on flexed posture and chest function in
      older women with age-related hyperkyphosis.
AB  - [Purpose] The purpose of this study was to determine the effects of thorax
      correction exercises on flexed posture and chest function in older women with age
      related hyperkyphosis. [Subjects and Methods] The study participants included 41
      elderly women who were divided into a thorax correction exercise group (n = 20)
      and a control group (n = 21). Participants in the exercise group completed a
      specific exercise program that included breathing correction, thorax mobility,
      thorax stability, and thorax alignment training performed twice per week, 1 hour
      each session, for 8 weeks. Outcome measures included the flexed posture (thoracic
      kyphosis angle, forward head posture) and chest function (vital capacity, forced
      expiratory volume in a second, and chest expansion length). [Results]
      Participants in the thorax correction exercise group demonstrated significantly
      greater improvements in thoracic kyphosis angle, forward head, and chest
      expansion than those in the control group. [Conclusion] This study provides a
      promising exercise intervention that may improve flexed posture and chest
      function in older women with age-related hyperkyphosis. 

PMID- 25995580
TI  - The effect of a pelvis-concentrated exercise program on male college students'
      body alignment and foot base pressure.
AB  - [Purpose] The aim of this study was to examine the effect of a pelvis
      concentrated exercise program and walking on the changes in body shape and foot
      base pressure. [Subjects and Methods] Thirty adults from K University in Busan,
      Republic of Korea, were randomly divided into the Swiss-ball exercise group and
      McKenzie exercise group, and they conducted exercise for 40 min 3 times a week
      for 6 weeks. [Results] Global postural system results and foot base pressure
      significantly decreased in both groups. A comparison of foot base pressure after
      the intervention between the two groups revealed that the Swiss-ball exercise
      group exhibited a greater reduction than the McKenzie exercise group.
      [Conclusion] The results of this study indicated that the Swiss-ball exercise may
      improve posture and foot base pressure in male adults. 

PMID- 25995581
TI  - The effects of horseback riding on body mass index and gait in obese women.
AB  - [Purpose] The aim of this study was to examine the effect of horseback riding on
      body mass index (BMI) and gait in obese women. [Subjects and Methods] Twenty-four
      obese women residing in Seoul and Gyeonggi-do were randomly divided into a
      horseback riding group and a walking group and conducted their respective
      exercises 3 times a week for 8 weeks. [Results] Step length increased
      significantly and BMI and width of the base of support significantly decreased in
      both groups. A comparison of BMI and width of the base of support after the
      intervention between the two groups revealed that the horseback riding group
      showed larger decreases than the walking group. [Conclusion] The result of this
      study indicated that the horseback riding may improve gait ability and obesity. 

PMID- 25995582
TI  - The relationship between motor recovery and gait velocity during dual tasks in
      patients with chronic stroke.
AB  - [Purpose] The aims of this study were to identify the relationship between motor
      recovery and gait velocity during dual tasks in patients with chronic stroke and
      determine automatic gait ability following stroke. [Subjects and Methods] Thirty
      three outpatients and twelve healthy subjects participated in a cross-sectional
      assessment. Community ambulation was assessed using a self-administered
      questionnaire. Outcome measures included the Motricity index, Berg Balance Scale,
      and gait speed under three conditions (self-paced ambulation for 10 m, ambulation
      while performing dual cognitive tasks, and ambulation while performing dual
      manual tasks). Gait automaticity was calculated. [Results] No significant
      differences were observed for muscle strength or balance between the limited
      community ambulation and the community ambulation groups. However, a significant
      difference in gait velocity was observed between the groups under the three
      conditions. In particular, a significant difference was detected only in the
      limited community ambulation group depending on the level of motor function
      recovery during cognitive and manual dual task ambulation. Additionally, we
      revealed that the community ambulation group had a lower level of gait
      automaticity compared with that in the normal group. [Conclusion] Our results
      show the influence of motor recovery on the change in gait velocity depending on
      the task if a patient is limitedly ambulatory. We revealed that community
      ambulators did not have a sufficient level of gait automaticity. 

PMID- 25995583
TI  - The effect of weight-bearing exercise and non-weight-bearing exercise on gait in
      rats with sciatic nerve crush injury.
AB  - [Purpose] The purpose of this study was to access the effect of weight bearing
      exercise (treadmill exercise) and non-weight-bearing exercise (swimming exercise)
      on gait in the recovery process after a sciatic nerve crush injury. [Subjects and
      Methods] Rats were randomly divided into a swimming group (n=3) with non-weight
      bearing exercise after a sciatic nerve crush and a treadmill group (n=3) with
      weight bearing exercise after a sciatic nerve crush. Dartfish is a program that
      can analyze and interpret motion through video images. The knee lateral
      epicondyle, lateral malleolus, and metatarsophalangeal joint of the fifth toe
      were marked by black dots before recording. [Results] There were significant
      differences in TOK (knee angle toe off) and ICK (knee angle at initial contact)
      in the swimming group and in TOK, ICA (ankle angle at initial contact), and ICK
      in the treadmill group. In comparison between groups, there were significant
      differences in TOA (ankle angle in toe off) and ICA at the 7th day. [Conclusion]
      There was no difference between weight bearing and non-weight-bearing exercise in
      sciatic nerve damage, and both exercises accelerated the recovery process in this
      study. 

PMID- 25995584
TI  - Antioxidant effect of Phyllanthus amarus after moderate-intensity exercise in
      sedentary males: a randomized crossover (double-blind) study.
AB  - [Purpose] We aimed to evaluate the effects of Phyllanthus amarus (PA) on
      oxidative stress and damage, inflammation, and soreness in muscle after a single
      session of moderate-intensity exercise. [Subjects and Methods] Twelve men
      randomly participated in 2, three-day phases with a one-week washout period. On
      the first day, participants consumed two capsules of PA or placebo control (CTL)
      before 20 min of cycling. They then consumed four capsules on the same day after
      exercise and six capsules/day for the next two days. Blood samples were obtained
      before, immediately after exercise and 24 h and 48 h after exercise. The pain
      tolerance was measured at both legs. [Results] Plasma vitamin C levels in the PA
      group were higher than those in the CTL group after exercise. At 48 h after
      exercise, vitamin C levels were higher in the PA group, but those in the CTL
      group were lower than the pre-exercise levels. However, plasma levels of creatine
      kinase were increased in both groups after exercise compared with the pre
      exercise levels. The neutrophil count was higher immediately after exercise than
      the pre-exercise levels in the CTL group. [Conclusion] Acute supplementation with
      PA improves antioxidant status after a single session of moderate-intensity
      exercise. 

PMID- 25995585
TI  - Synergistic effect of a rehabilitation program and treadmill exercise on pain and
      dysfunction in patients with chronic low back pain.
AB  - [Purpose] The present study examined the influence of treadmill exercise added to
      a low back pain rehabilitation program on low back extensor strength, pain, and
      dysfunction in chronic low back pain patients. [Subjects and Methods] Twenty men
      aged 22-36 years with chronic low back pain were randomly divided into
      experimental and control groups of 10 patients each. Both groups underwent a low
      back pain rehabilitation program lasting 30 min each, thrice/week for 8 weeks.
      The experimental group was prescribed an additional 30 min of treadmill exercise
      without a slope at a speed of 3.0-3.5 km/h, at which patients could walk
      comfortably. Low back extensor strength was tested using the Medx lumbar
      extension machine, pain level was tested, using the visual analog scale, and
      dysfunction was tested, using the Oswestry Low Back Pain Disability
      Questionnaire. [Results] Changes in low back extensor strength by angle showed
      significant interaction effects between measurement time and group at 12 degrees
      , 24 degrees , and 36 degrees . The results of the visual analog scale and
      Oswestry Questionnaire showed a decreasing trend after the experiment in both
      groups. However, there was no interaction effect of the additional treadmill
      exercise in the experimental group. [Conclusion] The combination of a low back
      pain rehabilitation program and treadmill exercise has a synergistic effect, to
      some extent, on the improvement of low back extensor strength and should be
      considered for treatment and rehabilitation of low back pain patients. 

PMID- 25995586
TI  - Effects of body awareness training on mild visuospatial neglect in patients with
      acute stroke: a pilot randomized controlled trial.
AB  - [Purpose] This study aimed to investigate the effects of body awareness training
      (BAT) on mild visuospatial neglect in patients following acute stroke. [Subjects]
      The subjects were 12 stroke patients randomly assigned to either the experimental
      group (n1=6) or control group (n2=6). [Methods] The experimental group underwent
      BAT for 15 minutes and then task-oriented training for 30 minutes a day, five
      times a week for three weeks. The control group underwent task-oriented training
      for 30 minutes a day, five times a week for three weeks. Assessments were made
      using the Motor-free Visual Perception Test (MVPT), Line Bisection Test (LBT),
      and modified Barthel index (MBI). [Results] Following the interventions, the
      experimental group showed a significant change in MVPT, LBT, and MBI scores.
      [Conclusion] The results of this study suggest the feasibility and suitability of
      BAT with task-oriented training for mild visuospatial neglect in patients with
      acute stroke. 

PMID- 25995587
TI  - Effect of initial position on the muscle activity of the hip extensors and amount
      of pelvic tilt during prone hip extension.
AB  - [Purpose] The aim of this study was to identify the effects of initial position
      of the hip joint with changes in the hip joint angle on the respective muscle
      activities of the bilateral erector spinae (ES), unilateral gluteus maximus (GM),
      and biceps femoris (BF) and the amount of pelvic anterior tilt during prone hip
      extension (PHE). [Subjects] Fifteen healthy volunteers were enrolled in this
      study. [Methods] The subjects performed PHE in three positions: neutral, 20
      degrees , and 45 degrees  flexed hip joint. The activities of the ES, GM, and BF
      were measured using surface electromyography, and kinematic values for pelvic
      anterior tilt were calculated using a motion capture system. [Results] There was
      a significant decrease in muscle activity of the contralateral ES at 45 degrees ,
      and an increase in the GM muscle activity and decrease in the BF muscle activity
      at 20 degrees . The amount of pelvic anterior tilt was lower at 20 degrees .
      [Conclusion] These results suggest that a hip flexion position of 20 degrees 
      would have an advantage over the other measured positions. 

PMID- 25995589
TI  - Comparison of the effect of weight-bearing and non-weight-bearing positions on
      knee position sense in patients with chronic stroke.
AB  - [Purpose] The purpose of this study was to investigate the knee joint
      proprioception in weight-bearing (WB) and non-weight-bearing (NWB) positions and
      to study the difference between the methods in chronic stroke patients. [Subjects
      and Methods] The subjects were 15 stroke patients who were randomly scheduled to
      perform both positions by a physical therapist not involved in the study. The
      subjects performed the positions (WB and NWB) based on a randomized controlled
      cross-sectional design. WB subjects were positioned in one-leg standing to assess
      the knee joint position sense. NWB subjects were instructed to sit comfortably in
      a chair and maintain the knees at 90 degrees  of flexion with the leg out of the
      plinth. [Results] The results revealed that the WB position showed a significant
      difference in knee position sense. The proprioception sense in the WB position
      was a higher than that in the NWB position. [Conclusion] The knee proprioception
      of chronic stroke patients differs between the weight-bearing and non-weight
      bearing positions. 

PMID- 25995588
TI  - Reliability and reproducibility of interapical distance assessment of the lateral
      deviation of vertebrae in scoliosis.
AB  - [Purpose] The purpose of this study was to investigate the interobserver
      reliability and intraobserver reproducibility of interapical distance (IAD) and
      to analyze its correlation with the Cobb angle (CA). [Subjects and Methods] IAD,
      a handy tool for assessment of the lateral deviation of vertebrae with a metric
      scale, was defined as the horizontal distance between one apical vertebra and its
      counterpart, the opposite apical vertebra in the case of a double curve and the
      farthest vertebra in the case of a single curve. Fifty full-length, standing
      anteroposterior radiographs of "idiopathic scoliosis" were reviewed. Three
      investigators independently measure the CA and IAD at the same time and
      remeasured the IAD on the same radiograph a week later. [Results] There was no
      interobserver difference (reliability) in the measurement of IAD or statistical
      differences in intraobserver reproducibility for each observer. IAD was well
      correlated with the CA for each observer (r=0.765, r=0.737, and r=0.764).
      [Conclusion] IAD is useful when assessing lateral deviation in scoliosis and may
      be a reliable and reproducible index that is well correlated with the CA, and it
      can be used as a supplementary measure to describe the overall derangement of
      scoliosis in the coronal plane. 

PMID- 25995590
TI  - Differences in onset timing between the vastus medialis and lateralis during
      concentric knee contraction in individuals with genu varum or valgum.
AB  - [Purpose] The purpose of this study was to investigate the difference in onset
      timing between the vastus medialis and lateralis among the different knee
      alignments, as well as the best isokinetic angular velocity for an isokinetic
      concentric contraction. [Subjects] Fifty-two adults (20 with genu varum, 12 genu
      valgum, and 20 controls) were enrolled in this study. Subjects with > 4 cm
      between the medial epicondyles of the knee were placed in the genu varum group,
      whereas subjects with > 4 cm between the medial malleolus of the ankle were
      placed in the genu valgum group. [Methods] Surface electromyography was used to
      measure the onset times of the vastus medialis and vastus lateralis during
      concentric contractions at 30, 60, and 90 degrees /sec. [Results] The vastus
      lateralis showed more delayed firing than the vastus medialis in the genu varum
      group, whereas vastus medialis firing was delayed more than that of the vastus
      lateralis in the genu valgum group. No differences in onset timing were observed
      between the vastus medialis and lateralis according the different angular
      velocities during concentric contractions in all three groups. [Conclusion] Genu
      varum and valgum affect quadriceps firing. Therefore, selective rehabilitation
      training of the quadriceps femoris should be considered to prevent pain or knee
      malalignment deformities. 

PMID- 25995591
TI  - Effects of a functional foot orthosis on the knee angle in the sagittal plane of
      college students in their 20s with flatfoot.
AB  - [Purpose] The purpose of this study was to examine the effects of a functional
      foot orthosis on the knee angle in the sagittal plane of college students in
      their 20s who had flatfoot. [Subjects and Methods] The subjects of this study
      were 20 college students diagnosed as having flatfoot. The variations of their
      knee angle (Q-angle) in the sagittal plane during the stance phase were measured
      using the VICON Motion System (Vicon, Hansung, Korea) before and while wearing a
      foot orthosis. The experimental data were analyzed using SPSS 12.0 for Windows.
      [Results] The Q-angle in the test group during the stance phase showed
      statistically significant declines on the right and left sides while wearing the
      foot orthosis during the gait-phases of loading response and midstance. During
      initial contact, terminal stance, and preswing, the Q-angle also decreased on the
      right and left sides after wearing the foot orthosis, but the changes were not
      statistically significant. [Conclusion] The college students with flatfoot
      exhibited declines in the Q-angle in the sagittal plane while wearing a foot
      orthosis. In this regard, the application of active gait training using orthotic
      shoes for long hours is likely to help individuals with flatfoot to achieve
      normal gait. 

PMID- 25995592
TI  - Effects of trunk rotation induced treadmill gait training on gait of stroke
      patients: a randomized controlled trial.
AB  - [Purpose] This study was conducted to find out the effect of arm swing during
      treadmill training on the gait of stroke patients. [Subjects and Methods] This
      study subjects were 20 stroke subjects patients who were randomly assigned to
      either the experimental group (EG) or the control group (CG), 10 subjects in each
      group. Therapists induced arm swing of affected side of EG subjects using Nordic
      poles, while subjects in CG had the affected arm restricted to prevent arm swing.
      Training was performed for 30 minutes, 3 times a week for 4 weeks. The timed up
      and go test (TUG), the dynamic gait index (DGI) and the 6-minute walk test (6MWT)
      were assessed before and after the training. [Results] After the training, there
      were no significant differences in the TUG times of EG and CG. There were
      significant differences in the DGI and the 6-minute walking distance of EG, but
      not of CG. There were also significant differences in the improvements of the DGI
      and the 6-minute walking distance between the groups. [Conclusion] Arm swing
      training had a positive effect on patients' gait ability. Further studies are
      required to generalize the results of this study. 

PMID- 25995593
TI  - Analysis of cortical activation during three types of therapeutic activity.
AB  - [Purpose] The objective of this study was to investigate changes from resting of
      the evoked cortical activity when participants performed three levels of
      therapeutic activities. [Subjects and Methods] Twenty-five students participated
      in this study. Changes in the amplitude of 16 pairs of evoked potentials were
      compared for three different activities: adjunctive, enabling, and purposeful.
      Data were analyzed using descriptive statistics and one-way ANOVA. [Results]
      Significant differences were found among the selected three activities for the
      Alpha 1 waveform. The complexity hierarchy was confirmed by descriptive
      statistics, as well as analyses of the three brain regions: central position
      (motor) Beta 1; parietal lobes, Beta 2, and occipital lobes, Alpha 1. In each
      instance, purposeful activity was confirmed as the most complex activity,
      followed by enabling, and then adjunctive. [Conclusion] This study will provide
      rehabilitation professionals with valuable information regarding what type of
      activity they should choose for a correct level of therapeutic challenge when
      they work with patients to plan meaningful interventions. 

PMID- 25995594
TI  - Decreasing fall risk in spinocerebellar ataxia.
AB  - [Purpose] Spinocerebellar ataxia consists of a group of autosomal dominant
      disorders that cause progressive degeneration, mainly in the cerebellum and its
      connections. Falls, which are a significant concern of this condition, reduce
      patients' mobility, deteriorate their health and have physical and social
      consequences. The aim of this study was to test the effectiveness of a modified
      protocol for improving balance and diminishing the fall risk of spinocerebellar
      ataxia patients exclusively. [Subjects and Methods] Exercises aiming to improve
      static and dynamic balance, whole body movements, measures to prevent falls and
      falling strategies were performed twice per week for four weeks by 11
      spinocerebellar ataxia patients. Balance was evaluated using the Berg Balance
      Scale. [Results] The results show that there was a significant increase in Berg
      Balance Scale scores after the interventions (Wilcoxon p=0.0034). [Conclusion]
      This study demonstrated that the modified protocol is effective at reducing the
      fall risk of spinocerebellar ataxia patients. This protocol may be a useful
      option for appropriately coping with falls caused by spinocerebellar ataxia. 

PMID- 25995595
TI  - Correlation of stress and muscle activity of patients with different degrees of
      temporomandibular disorder.
AB  - [Purpose] Temporomandibular disorder is one of the many different adverse health
      conditions that can be triggered by stress. Therefore, a biopsychosocial model
      has been proposed to characterize the multifactorial nature of temporomandibular
      disorder. The aim of the present study was investigate the correlation of
      salivary cortisol levels with the activities of the masseter and anterior
      temporal muscles of patients with different degrees of temporomandibular
      disorder. [Subjects and Methods] Forty-nine women between 18 and 40 years of age
      with a diagnosis of myogenous temporomandibular disorder based on the Research
      Diagnostic Criteria for temporomandibular disorders were evaluated using the
      Fonseca Index to determine the degree of the disorder. Salivary cortisol levels
      were determined and surface electromyography was used to evaluate electrical
      activity in the masticatory muscles. [Results] Positive correlations were found
      among the degree of temporomandibular disorder, electromyographic activity and
      salivary cortisol: as women with more severe temporomandibular disorder had
      greater electrical activity in the muscles analyzed, especially the anterior
      temporal muscle, and higher levels of cortisol. [Conclusion] Muscle activity was
      greater among individuals with severe temporomandibular disorder and positive
      correlations were found among electromyographic activity, salivary cortisol and
      the degree of temporomandibular disorder severity. 

PMID- 25995596
TI  - Relationship between the intensity of physical activity and depressive symptoms
      among Korean adults: analysis of Korea Health Panel data.
AB  - [Purpose] The aim of this study was to examine the relationship between the
      intensity of physical activity and symptoms of depression. [Subjects and Methods]
      We analyzed the influence of different intensities of physical activity on
      depressive symptoms using the data of 12,350 adults over the age of 20 years who
      had completed the 2011 Korea Health Panel. After controlling for confounding
      variables, a multivariable logistic regression analysis was conducted to identify
      the association between the intensity of physical activity and depressive
      symptoms. [Results] The results showed that vigorous physical activity had a
      significant effect on depressive symptoms. The incidence of depressive symptoms
      was 1.487 (95% CI 1.137, 1.943) OR higher among people who did not participate in
      regular activity than it was among those who took part in regular intense
      physical activity. [Conclusion] It appears that physical activity affects
      depressive symptoms, a result which is in agreement with previous studies.
      However, we also showed a difference in influence according to activity
      intensity. Thus, the intensity of physical activity should be considered when
      developing physical activity programs for improving depressive symptoms. 

PMID- 25995598
TI  - The relationship between breast density and bone mineral density after menopause.
AB  - [Purpose] The purpose of this study was to analyze the relationship between
      breast density and bone mineral density after menopause. [Subjects and Methods]
      The subjects were 130 patients who participated in a bone densitometry test and
      had a mammogram taken between January 1st, 2013 to October 1st, 2014. The
      mammograms were scored breast imaging-reporting and data system. Grade 1
      indicates almost only fat, Grade 2 indicates fibroglandular densities, Grade 3
      indicates heterogeneously dense tissue, and Grade 4 indicates an extreme density.
      Correlation analysis was carried out to investigate the relationship between
      breast density grades and bone mineral densities by age and body mass index.
      [Results] Breast density had a close relationship with age (-0.59), Body mass
      index (-0.39), and T-score (0.29). The results indicate that as age and body mass
      index increase, the grade of the breast density decreases, and as the T-score
      increases, the grade increases. [Conclusion] A precise evaluation of the of
      breast cancer risk associated with breast density should be conducted as a large
      scale prospective study for women in Korea. 

PMID- 25995597
TI  - Aerobic exercise improves oxidant-antioxidant balance in patients with rheumatoid
      arthritis.
AB  - [Purpose] Although oxidative stress is known to be present in rheumatoid
      arthritis (RA), the effects of exercise on oxidative parameters are unknown. The
      aim of this study was to investigate the effects of acute aerobic exercise on
      serum oxidant and antioxidant levels in patients with RA. [Subjects and Methods]
      Sixteen patients with RA and 10 age-matched healthy volunteers participated in
      this study. All participants wore polar telemeters and walked on a treadmill for
      30 minutes at a speed eliciting 60-75% of maximal heart rates. Blood samples were
      obtained before, immediately and 24 hours after exercise and malondialdehyde
      (MDA) and total sulfhydrile group (RSH) levels were measured. [Results] Both
      groups had similar heart rates during the test but the treadmill speed of the RA
      patients was significantly lower than that of the healthy volunteers. Serum MDA
      levels were lower than in both groups immediately after exercise, with greater
      decrements in the RA patients than controls. MDA levels returned to baseline 24
      hours after the exercise only in the controls; they remained low in the RA
      patients. There was a slight increase in serum RSH levels after exercise compared
      to baseline in both groups. [Conclusion] Moderate intensity treadmill exercise
      did not have any adverse effect on the oxidant-antioxidant balance. The results
      suggest that such an exercise may be safely added to the rehabilitation program
      of RA for additional antioxidant effects. Morever, this antioxidant environment
      is maintained longer in RA patients. 

PMID- 25995599
TI  - How effective is the early fast treadmill gait speed training for stroke patients
      at the 2nd week after admission: comparison with comfortable gait speed at the
      6th week.
AB  - [Purpose] The purpose of this study was to find whether a fast treadmill gait
      training speed is effective for the gait training of stroke patients in the early
      rehabilitation stage. [Subjects and Methods] Thirty-nine stroke patients were the
      subjects of our investigation. They walked on a treadmill with handrail supports
      at a fast speed (130% of their comfortable gait speed in the 2nd week). The
      treadmill gaits of the patients were recorded using a 3-dimensional analysis
      system at two and six weeks after their admissions. Intraclass Correlation
      Coefficients (ICC) of the temporal and spatial parameters of the two periods were
      statistically analyzed. [Results] For all of the patients, the ICCs of the
      measured parameters were greater than 0.58. In the case of patients whose gait
      speeds of the two periods were close, the ICC units were greater than 0.7.
      [Conclusion] The fast gait speed training allowed us to expose the patients to a
      gait speed that they were expected to acquire at a later stage of their
      rehabilitation. This training method was found to be beneficial for the mildly
      paralyzed patients. 

PMID- 25995600
TI  - Relationship between joint motion and acceleration during single-leg standing in
      healthy male adults.
AB  - [Purpose] The purpose of this study was to clarify the relationship between
      acceleration and joint movement by synchronizing accelerometers and a three
      dimensional motion analysis system, and to show the utility of an accelerometer
      as a postural control assessment tool. [Subjects and Methods] Head, lumbar, shank
      accelerations and various joint angles during single-leg standing were measured
      of 20 healthy males. Root mean squares of acceleration and joint angle were
      calculated. Fast Fourier transform analysis was performed for head, lumbar, and
      shank accelerations, and the median frequencies were calculated. Then, principal
      component analysis was performed for the median frequency of each acceleration.
      Stepwise multiple regression analysis was also used to examine the relationship
      between joint angle and acceleration. [Results] The score of the first principal
      component was highest for shank acceleration, while that of the second principal
      component was highest for lumbar and head accelerations. In multiple regression
      analysis, hip flexion/extension and adduction/abduction were identified as
      variables associated with head acceleration. [Conclusion] We were able to confirm
      the aggregation of acceleration into two components, which we interpreted as
      postural control strategies using primarily the ankle and hip joints.
      Furthermore, though multiple regression analysis, we were able to clarify the
      joint movement indicated by acceleration of each segment. 

PMID- 25995601
TI  - Effect of treadmill walking with ankle stretching orthosis on ankle flexibility
      and gait.
AB  - [Purpose] The purpose of this study was to evaluate the kinematics of the ankle
      in the lunge to estabilish effectiveness of an ankle stretching orthosis (ASO) on
      the ankle dorsiflexion range of motion (ROM) of individuals with limited
      dorsiflexion ROM. [Subjects and Methods] Forty ankles with decreased dorsiflexion
      ROM of 20 participants were evaluated in this study. After wearing the ASO,
      participants walked on a treadmill for 15 minutes. Participants walked on the
      treadmill at a self-selected comfortable speed. Ankle dorsiflexion ROM, maximum
      dorsiflexion ROM before heel-off, and time to heel-off during the stance phase of
      gait were measured before and after 15 minutes of treadmill walking with the ASO.
      The differences in all variables between before and after treadmill walking with
      ASO were analyzed using the paired t-test. [Results] Ankle active and passive
      ROM, and dorsiflexion ROM during lunge increased significantly after treadmill
      walking with ASO. Treadmill walking with the ASO significantly increased the
      angle of maximal dorsiflexion before heel-off and time to heel-off during the
      stance phase. [Conclusion] The results of this study show that treadmill walking
      with the ASO effectively improved ankle flexibility and restored the normal gait
      pattern of the ankle joint by increasing dorsiflexion ROM, maximal angle of
      dorsiflexion, and time to heel-off in the stance phase. 

PMID- 25995602
TI  - Relationship between knee alignment and the electromyographic activity of
      quadriceps muscles in patients with knee osteoarthritis.
AB  - [Purpose] We evaluated the relationship between knee alignment and the
      electromyographic (EMG) activity of the vastus medialis (VM) to the vastus
      lateralis (VL) muscles in patients with knee osteoarthritis (OA) in a cross
      sectional study. [Subjects and Methods] Forty subjects with knee OA were assessed
      by anatomic radiographic knee alignment and the VM/VL ratio was calculated.
      Surface EMG from both the VM and VL muscles were evaluated during maximal
      isometric contraction at 60 degrees  knee flexion. Simultaneously, peak
      quadriceps torque was assessed using an isokinetic dynamometer. Subjects were
      categorized into low, moderate, and high varus groups according to knee
      malalignment. The peak quadriceps torque and VM/VL ratio across groups, and their
      relationships with varus malalignment were analyzed. [Results] All subjects had
      medial compartment OA and the VM/VL ratio of all subjects was 1.31 +/- 0.28 (mean
      +/- SD). There were no significant differences in the peak quadriceps torque or
      VM/VL ratios across the groups nor were there any significant relationships with
      varus malalignment. [Conclusion] The VM/VL ratio and peak quadriceps torque were
      not associated with the severity of knee varus malalignment. 

PMID- 25995603
TI  - Effects of auditory feedback during gait training on hemiplegic patients' weight
      bearing and dynamic balance ability.
AB  - [Purpose] This study examined the effects of auditory feedback during gait on the
      weight bearing of patients with hemiplegia resulting from a stroke. [Subjects]
      Thirty hemiplegic patients participated in this experiment and they were randomly
      allocated to an experimental group and a control group. [Methods] Both groups
      received neuro-developmental treatment for four weeks and the experimental group
      additionally received auditory feedback during gait training. In order to examine
      auditory feedback effects on weight bearing during gait, a motion analysis system
      GAITRite was used to measure the duration of the stance phase and single limb
      stance phase of the subjects. [Results] The experimental group showed
      statistically significant improvements in the duration of the stance phase and
      single limb stance phase of the paretic side and the results of the Timed Up and
      Go Test after the training. [Conclusion] Auditory feedback during gait training
      significantly improved the duration of the stance phase and single limb stance
      phase of hemiplegic stroke patients. 

PMID- 25995604
TI  - Long-term effects of therapeutic exercise on nonspecific chronic neck pain: a
      literature review.
AB  - [Purpose] Nonspecific neck pain is a common musculoskeletal disease. Therapeutic
      exercise has been shown to improve pain and disability in short-term and midterm
      follow-ups. This study performed a literature review of the long-term effects of
      therapeutic exercise on subjects with nonspecific chronic neck pain. [Subjects
      and Methods] The databases of the CINAHL, MEDLINE, PEDro and PubMed were used.
      Randomized controlled trials (RCT) published from January 2000 to January 2014
      and explicitly including a one-year follow-up were identified. [Results] Only six
      articles were included in this review. They had scores of 5 to 8 points on the
      PEDro scale, and the level of evidence was grade I. The study results show that
      the main exercises used were cervical strengthening and endurance training
      exercise. Short-term exercises (10 to 12 weeks) helped to improve the body
      function, structure, activity and participation immediately after the
      intervention, but not at the long-term follow-up. On the other hand, long-term
      interventions (1 year) resulted in improvements in body function and structure at
      the 3 year follow-up. [Conclusion] The results of the six high-quality studies
      suggest that long-term exercise have long-term benefits for patients with
      nonspecific neck pain in terms of body function and structure. 

PMID- 25995605
TI  - Effects of modified bridging exercises on static postural control of a poststroke
      hemiplegic patient who had received surgery for lumbar spinal stenosis: a case
      report.
AB  - [Purpose] This study investigated the efficacy on postural control of a bridging
      exercise in order to suggest a pertinent procedure for the bridging exercise.
      [Subject] One poststroke hemiplegic patient who had received surgery for lumbar
      spinal stenosis participated in this study [Methods] A reverse ABAB single-case
      experimental design was used. To assess postural control, foot pressure and the
      stability limit test were evalulated once a week a total of 4 times during the
      intervention period. [Results] Noticeable improvement in the distribution of foot
      pressure and increased stability limit were shown after performing the bridging
      exercise supervised by a physical therapist. [Conclusion] Bridging exercise on a
      plinth is effective at balancing body weight-bearing and resulted in the patient
      putting her weight on both feet evenly and in both the anterior and posterior
      directions. 

PMID- 25995606
TI  - The effects of vestibular stimulation on a child with hypotonic cerebral palsy.
AB  - [Purpose] The purpose of this case report is to present the effects of vestibular
      stimulation on a child with hypotonic cerebral palsy through the use of swings.
      [Case Description] The subject was a 19-month-old boy with a diagnosis of
      hypotonic cerebral palsy (CP) and oscillating nystagmus. The subject had received
      both physical therapy and occupational therapy two times per week since he was 5
      months old but showed little to no improvement. [Methods] Pre and post
      intervention tests were completed by the researcher using the Bayley Scales of
      Infant and Toddler Development II. The subject was provided with vestibular
      stimulation 3 times per week for 10 weeks in 1 hour sessions conducted by his
      mother as instructed by the researcher. During this research all other therapies
      were stopped to determine the effects of the vestibular stimulation and to
      exclude the effects of other therapies. [Results] The subject demonstrated
      improvement of 4 months in motor skills and of 3 months in mental skills as shown
      by the Bayley Scales of Infant and Toddler Development II. [Conclusion]
      Vestibular stimulation was effective in improving postural control, movement,
      emotional well-being, and social participation of a child with hypotonic cerebral
      palsy. 

PMID- 25995607
TI  - College Students' Revenge Goals Across Friend, Romantic Partner, and Roommate
      Contexts: The Role of Interpretations and Emotions.
AB  - Residential college environments provide young people with distinctive
      relationship opportunities and challenges. A major purpose of the present study
      was to learn whether college students respond differently to conflict-of-interest
      vignettes in three different relationship contexts. Students were more likely to
      make negative interpretations about their romantic partner's behavior than they
      did about their friend's or roommate's behavior. They were also more likely to
      feel angry and hurt and to endorse hostile goals and strategies with romantic
      partners. A second major purpose was to learn about the types of interpretations
      and emotions associated with revenge goals in conflict-of-interest situations.
      Results indicated that interpreting the other person's actions as disrespectful
      and as rejecting was related to revenge goals and also predicted to revenge goals
      beyond the contributions of anger and hurt feelings.

PMID- 25995608
TI  - Injection and sexual risk practices among young heroin users in Hanoi, Vietnam.
AB  - Epidemiological data in Vietnam shows high HIV prevalence rates among injection
      drug users, especially in urban centres. However, there are limited data on
      specific practices used to prepare and inject drugs or on sexual practices among
      Vietnamese injectors. A street-based cross-sectional interview was conducted with
      862 heroin injectors in Hanoi, Vietnam, to collect such data. Variability was
      seen in both injection and sexual risk, with 12.9% of current injectors reporting
      at least one unsafe method of drug sharing and 57.1% reporting unsafe sex in the
      past 30 days. These risks were strongly associated with those who engaged in
      unsafe injection significantly more likely to engage in unsafe sex (69.4% vs.
      55.3%) and those engaging in unsafe sex significantly more likely to engage in
      unsafe injection (15.7% vs. 9.2%). These findings highlight the overlap of
      injection and sexual risk practices among Vietnamese heroin users and suggest the
      need for strong, broadly targeted HIV prevention activities among this
      population.

PMID- 25995609
TI  - Specific Language Impairment in Children: A Comparison of English and Swedish.
AB  - We report a cross-linguistic investigation of English- and Swedish-speaking
      children with specific language impairment (SLI) in an attempt to determine
      whether Wexler's (1998; 2003) (Extended) Unique Checking Constraint (EUCC) can
      account for the grammatical profiles of these groups of children. In Study I, a
      group of Swedish-speaking preschoolers with SLI showed greater use of finite verb
      inflections and copula forms than a group of English-speaking preschoolers with
      SLI, even though the two groups were carefully matched according to both age and
      severity of language impairment. In Study II, the same Swedish-speaking children
      with SLI showed high levels of appropriate verb-second use with finite verbs.
      However, they were less proficient in this regard than a group of younger
      typically developing Swedish children with similar mean lengths of utterance. The
      findings from both studies were generally compatible with predictions based on
      the EUCC. Issues in need of future investigation are discussed.

PMID- 25995610
TI  - Longitudinal Influence of Paternal Distress on Children's Representations of
      Fathers, Family Cohesion, and Family Conflict.
AB  - A parent's distress is known to color children's experiences of their families.
      Studies, however, have rarely focused on the levels of distress experienced by
      fathers, and in particular, as they affect the emotional experiences of their
      children. We examine the impact that fathers' experience of distress throughout
      their children's early years has on children's emerging narrative representations
      of father-child relationships and of family conflict and cohesion. In this
      longitudinal investigation, fathers of young children reported their distress on
      two occasions in relation to self, the marital relationship, and the family
      climate. Fathers also concurrently reported on their children's temperament,
      specifically negative emotionality. Children responded to story stem beginnings
      about challenging situations in the family and their narratives were scored for
      dysregulated negative-disciplinary and positive parental behaviors of fathers,
      family conflict themes, and family harmony themes. It was hypothesized that
      children of more distressed fathers would represent greater dysregulated
      fathering and higher levels of family conflict, and lower levels of positive
      fathering and family harmony than children of less distressed fathers. Further,
      the study examined whether this effect was mediated through the fathers' reports
      of their children's negative emotionality. Results partially supported the
      hypothesized direct and indirect effects. Children's narratives of negative
      disciplinary fathering and family conflict were more common in boys when fathers
      reported greater distress, and temperament ratings fully mediated this effect.
      However, their narratives of positive fathering and family harmony were not
      significantly affected. That positive family features were preserved in
      children's narratives even in the face of greater father distress suggests that
      families may be able to build resilience to internalized distress through these
      positive narrative features.

PMID- 25995612
TI  - Tube shunt coverage with gamma-irradiated cornea allograft (VisionGraft).
AB  - PURPOSE: To investigate the clinical outcomes of tube shunt coverage using
      sterile gamma-irradiated cornea allograft. PATIENTS AND METHODS: The Wills Eye
      Hospital Glaucoma Research Center retrospectively reviewed the medical records of
      165 patients who underwent glaucoma tube shunt procedures using sterile gamma
      irradiated cornea allograft (VisionGraft) between December 2012 and November
      2013. Demographic characteristics, type of tube shunt, and position were noted.
      Complications were recorded at 1 day; 1 week; 1, 3, 6, and 12 months; and on the
      final postoperative visit. RESULTS: One hundred and sixty-nine eyes of 165
      patients were included. The mean follow-up time was 4.8+/-3.5 (ranging from 1 to
      16) months. There was no evidence of immunological reaction, infection, or
      exposure in 166 eyes (98.2%). Three eyes (1.8%) experienced graft or tube
      exposure within the first 3 postoperative months. Two of the cases had underlying
      diseases: bullous pemphigoid and chronic allergic conjunctivitis. CONCLUSION:
      Coverage of tube shunts using gamma-irradiated cornea allograft had a low
      exposure rate and was well tolerated. The graft can be stored long term at room
      temperature and has an excellent postoperative cosmetic appearance.

PMID- 25995611
TI  - Prioritization of cancer-related genomic variants by SNP association network.
AB  - We have developed a general framework to construct an association network of
      single nucleotide polymorphisms (SNPs) (SNP association network, SAN) based on
      the functional interactions of genes located in the flanking regions of SNPs.
      SAN, which was constructed based on protein-protein interactions in the Human
      Protein Reference Database (HPRD), showed significantly enriched signals in both
      linkage disequilibrium (LD) and long-range chromatin interaction (Hi-C). We used
      this network to further develop two methods for predicting and prioritizing
      disease-associated genes from genome-wide association studies (GWASs). We found
      that random walk with restart (RWR) using SAN (RWR-SAN) can greatly improve the
      prediction of lung-cancer-associated genes by comparing RWR with the use of
      network in HPRD (AUC 0.81 vs 0.66). In a reanalysis of the GWAS dataset of age
      related macular degeneration (AMD), SAN could identify more potential AMD
      associated genes that were previously ranked lower in the GWAS study. The
      interactions in SAN could facilitate the study of complex diseases. 

PMID- 25995613
TI  - The metabolic syndrome and severity of diabetic retinopathy.
AB  - BACKGROUND: While metabolic syndrome has been strongly implicated as a risk
      factor for macrovascular diseases, such as stroke and cardiovascular disease, its
      relationship with microvascular diseases, including diabetic retinopathy, has
      been less defined. The purpose of this pilot study was to investigate the
      association between metabolic syndrome and the presence and severity of diabetic
      retinopathy. METHODS: A retrospective case-control chart review at the University
      of Iowa ophthalmology and primary care clinics included 100 patients with
      proliferative diabetic retinopathy (PDR), 100 patients with nonproliferative
      diabetic retinopathy (NPDR), 100 diabetic patients without diabetic retinopathy,
      and 100 nondiabetic patients who were randomly selected. Using the International
      Diabetes Foundation definition, the prevalence of metabolic syndrome and the
      number of components of metabolic syndrome were compared among these groups.
      RESULTS: The prevalence of metabolic syndrome in patients with diabetes was
      69.3%, which was significantly higher than that in patients without diabetes
      (27%; P<0.0001) (odds ratio [OR] =6.28; 95% confidence interval [CI]: 3.76-10.49;
      P=0.0004). However, there was no significant difference in the prevalence of
      metabolic syndrome between diabetics with and without diabetic retinopathy, with
      rates of 67.5% and 73%, respectively (P=0.36) (OR =0.77; 95% CI: 0.45-1.32;
      P=0.34). In addition, there was no significant difference between the PDR and
      NPDR groups, with rates of 63% and 72%, respectively (P=0.23) (OR =0.70; 95% CI:
      0.38-1.30; P=0.26). CONCLUSION: The metabolic syndrome was highly prevalent in
      patients with diabetes, but it was not associated with the presence or severity
      of retinopathy.

PMID- 25995614
TI  - Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice.
AB  - The current study describes novel multifunctional polymer-shelled microbubbles
      (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic
      applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs
      with an average diameter of 4 MUm stabilized by a biocompatible shell of
      polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the
      backscattered power (20 dB) acquired from the MBs' suspension. The values of
      attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were
      comparable with those reported for the soft tissue. Moreover, polymer MBs
      demonstrate increased stability compared with clinically approved contrast agents
      with a fracture threshold of about 900 kPa. In vitro chemiluminescence
      measurements demonstrated that dry powder of NO-loaded MBs releases its gas
      content in about 2 hours following an exponential decay profile with an
      exponential time constant equal to 36 minutes. The application of high-power
      ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline
      decreases the exponential time constant from 55 to 4 minutes in air-saturated
      solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound
      triggered release of NO is achieved. Cytotoxicity tests indicate that
      phagocytosis of the MBs by macrophages starts within 6-8 hours. This is a
      suitable time for initial diagnostics, treatment, and monitoring of the
      therapeutic effect using a single injection of the proposed multifunctional MBs. 

PMID- 25995615
TI  - Pharmacokinetics of mitragynine in man.
AB  - BACKGROUND: Kratom, known botanically as Mitragyna speciosa (Korth.), is an
      indigenous tree in Southeast Asia. Kratom is currently easily available worldwide
      via special shops and the Internet to use as a drug of abuse, opioid alternative,
      or pain killer. So far, the pharmacokinetics of this plant has been studied only
      in animals, and there is no such study in humans. The major abundant active
      alkaloid in Kratom, mitragynine, is one of the promising new chemical substances
      to be developed as a new drug. The aim of this study was to examine the
      pharmacokinetics of mitragynine and assess the linearity in pharmacokinetics in
      chronic users. METHODS: Since Kratom is illegal in Thailand, studies in healthy
      subjects would be unethical. We therefore conducted a prospective study by
      enrolling ten chronic, regular, healthy users. We adjusted the steady state in
      each subject by giving a known amount of Kratom tea for 7 days before
      commencement of the experiment. We admitted and gave different oral doses to
      subjects to confirm linearity in pharmacokinetics. The mitragynine blood
      concentrations at 17 times points and the urine concentrations during the 24-hour
      period were collected and measured by liquid chromatography-tandem mass
      spectrometry method. RESULTS: Ten male subjects completed the study without
      adverse reactions. The median duration of abuse was 1.75 years. We analyzed one
      subject separately due to the abnormal behavior of blood concentration. From data
      of nine subjects, the pharmacokinetic parameters established were time to reach
      the maximum plasma concentration (0.83+/-0.35 hour), terminal half-life (23.24+/
      16.07 hours), and the apparent volume of distribution (38.04+/-24.32 L/kg). The
      urine excretion of unchanged form was 0.14%. The pharmacokinetics were observed
      to be oral two-compartment model. CONCLUSION: This was the first pharmacokinetic
      study in humans, which demonstrated linearity and was consistent with the oral
      two-compartment model with a terminal half-life of about 1 day. The
      pharmacokinetic linearity and parameters reported are necessary pharmacological
      information of Kratom, and there is a possibility for it to be developed
      medically as a pain killer or better opioid substitute in the future.

PMID- 25995616
TI  - Preparation and clinical evaluation of nano-transferosomes for treatment of
      erectile dysfunction.
AB  - OBJECTIVE: The goal of the present study was to formulate topical nanocarriers of
      the low-cost vasodilator, papaverine hydrochloride (PH), as an alternative to the
      painful penile injections. The injections are used for both diagnosis and
      treatment of erectile dysfunction. Transdermal nano-transferosome (T), the
      ultraflexible nanoliposome, was used as a nanocarrier to enhance the penetration
      of the papaverine to the penis. METHODS: Different nano formulas were prepared
      and characterized for their encapsulation efficiency, particle size, zeta
      potential, and cumulative drug release. The formula acquired the best
      characteristics was incorporated into 2% (w/v) hydroxypropyl methylcellulose
      hydrogel base. The gel containing transferosomal papaverine hydrochloride (PH)
      and that containing free PH were clinically compared using color flow Doppler
      measurements. RESULTS: The results revealed that transferosome 3 (T3) had the
      highest entrapment efficiency approaching 72%, low particle size of 220 nm, and
      zeta potential of -33.4 mV. The formula released 73% of its initial drug content
      within 2 hours. The clinical evaluation showed the increase in the cavernous
      artery diameter from 0.53 mm to 0.78 mm and the increase in the peak systolic
      flow velocity from 5.95 cm/second to 12.2 cm/second, both of which were found to
      be significant at P<0.05. CONCLUSION: It is evident from the study that the
      transferosomes can be used as a carrier of papaverine hydrochloride for both
      diagnosis and treatment of the erectile dysfunction. This new strategy could be
      used successfully in the treatment of erectile dysfunction and in male impotency.

PMID- 25995617
TI  - Structural dynamics and inhibitor searching for Wnt-4 protein using comparative
      computational studies.
AB  - Wnt-4 (wingless mouse mammary tumor virus integration site-4) protein is involved
      in many crucial embryonic pathways regulating essential processes. Aberrant Wnt-4
      activity causes various anomalies leading to gastric, colon, or breast cancer.
      Wnt-4 is a conserved protein in structure and sequence. All Wnt proteins contain
      an unusual fold comprising of a thumb (or N-terminal domain) and index finger (or
      C-terminal domain) bifurcated by a palm domain. The aim of this study was to
      identify the best inhibitors of Wnt-4 that not only interact with Wnt-4 protein
      but also with the covalently bound acyl group to inhibit aberrant Wnt-4 activity.
      A systematic computational approach was used to analyze inhibition of Wnt-4.
      Palmitoleic acid was docked into Wnt-4 protein, followed by ligand-based virtual
      screening of nearly 209,847 compounds; conformer generation of 271 compounds
      resulted from extensive virtual screening and comparative docking of 10,531
      conformers of 271 unique compounds through GOLD (Genetic Optimization for Ligand
      Docking), AutoDock-Vina, and FRED (Fast Rigid Exhaustive Docking) was
      subsequently performed. Linux scripts was used to handle the libraries of
      compounds. The best compounds were selected on the basis of having maximum
      interactions to protein with bound palmitoleic acid. These represented lead
      inhibitors in further experiments. Palmitoleic acid is important for efficient
      Wnt activity, but aberrant Wnt-4 expression can be inhibited by designing
      inhibitors interacting with both protein and palmitoleic acid. 

PMID- 25995618
TI  - The mechanism of CCN1-enhanced retinal neovascularization in oxygen-induced
      retinopathy through PI3K/Akt-VEGF signaling pathway.
AB  - BACKGROUND: CCN1 (also called Cyr 61) is an extracellular matrix signaling
      molecule that has been implicated in neovascularization through its interactions
      with several endothelial integrin receptors. The roles of vascular endothelial
      growth factor (VEGF) in angiogenesis are well described. The aim of this study
      was to investigate the signal transduction mechanism of CCN1-PI3K/Akt-VEGF in
      retinopathy of prematurity (ROP), and the effects of CCN1 knockdown on ROP.
      METHODS: The oxygen-induced retinopathy (OIR) model was established in C57BL/6J
      mice exposed to a high concentration of oxygen. Retinas were obtained from the
      normoxia, OIR, OIR control (treated with scramble siRNA) and OIR treated (with
      CCN1 siRNA) groups. Retinal neovascularization (RNV) was qualitatively analyzed
      with ADPase staining and quantitatively analyzed by counting neovascular
      endothelial cell nuclei at postnatal day 17 when RNV reached a peak. mRNA level
      and protein expression of CCN1, p-Akt, and VEGF were measured by real-time PCR
      and Western blotting, and located with immunohistochemistry. RESULTS: CCN1
      depletion resulted in less neovascularization clock hour scores in the number of
      preretinal neovascular cells compared with the OIR treated group (1.28+/-0.83
      versus 4.80+/-0.82; and 7.12+/-2.50 versus 23.25+/-2.35, respectively, both
      P<0.05). Furthermore, CCN1, p-Akt and VEGF mRNA, and protein were significantly
      expressed in the retina of the OIR and OIR control groups. Intravitreal injection
      of CCN1 siRNA significantly reduced PI3K/Akt-VEGF pathway expression of the OIR
      mouse model (all P<0.05). CCN1 siRNA significantly enhanced the avascular area
      and avascular diameter of OIR model (P<0.05). CCN1 siRNA decreased the levels of
      IL-1beta, IL-6, and TNF-alpha significantly compared to the OIR group (P<0.05).
      CONCLUSION: These results suggest that CCN1 plays an important role in RNV via
      the PI3K/Akt-VEGF signaling pathway. CCN1 may be a potential target for the
      prevention and treatment of ROP.

PMID- 25995619
TI  - Enhanced anti-inflammatory potential of cinnamate-zinc layered hydroxide in
      lipopolysaccharide-stimulated RAW 264.7 macrophages.
AB  - BACKGROUND: Cinnamic acid (CA) is a phytochemical originally derived from
      Cinnamomum cassia, a plant with numerous pharmacological properties. The
      intercalation of CA with a nanocarrier, zinc layered hydroxide, produces
      cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized.
      Intercalation is expected to improve the solubility and cell specificity of CA.
      The nanocarrier will also protect CA from degradation and sustain its release.
      The aim of this study was to assess the effect of intercalation on the anti
      inflammatory capacity of CA. METHODS: In this study, the anti-inflammatory
      activity of ZCA was investigated and compared with that of nonintercalated CA.
      Evaluations were based on the capacity of ZCA and CA to modulate the release of
      nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha
      (TNF-alpha), IL-1beta, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells.
      Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2,
      inducible nitric oxide synthase, and nuclear factor kappa B (NF-kappaB), were
      examined. RESULTS: Although both ZCA and CA downregulated nitric oxide,
      prostaglandin E2, tumor necrosis factor alpha, IL-1beta, and IL-6, ZCA clearly
      displayed better activity. Similarly, expression of cyclooxygenase-2 and
      inducible nitric oxide synthase were inhibited in samples treated with ZCA and
      CA. The two compounds effectively inactivated the transcription factor NF-kappaB,
      but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA
      only. CONCLUSION: The present findings suggest that ZCA possesses better anti
      inflammatory potential than CA, while zinc layered hydroxide had little or no
      effect, and these results were comparable with the positive control.

PMID- 25995621
TI  - Erratum: Electronic health records and improved nursing management of chronic
      obstructive pulmonary disease [Corrigendum].
AB  - [This corrects the article on p. 495 in vol. 9, PMID: 25848228.]. 

PMID- 25995622
TI  - Development of a patient decision aid for type 2 diabetes mellitus for patients
      not achieving glycemic control on metformin alone.
AB  - PURPOSE: To describe the process used to develop an evidence-based patient
      decision aid (PDA) that facilitates shared decision-making for treatment
      intensification in inadequately controlled type 2 diabetes mellitus (T2DM)
      consistent with International Patient Decision Aids Standards. METHODS: A PDA was
      developed by a multidisciplinary steering committee of clinicians, patient
      advocate, nurse, certified diabetes educators, and decision scientist, using a
      systematic development process. The process included defining the PDA scope and
      purpose, outlining the framework, content creation, and designing for integration
      into clinical practice. This was accomplished through a review of the literature
      and publically available educational materials and input from practicing
      clinicians and patients during development and iteratively refining content based
      on input. Patients with poorly controlled T2DM on metformin considering
      additional medication assessed the PDA during a pilot. RESULTS: Testing
      identified six preference-sensitive domains important for choosing T2DM
      treatment: degree of glycemic response, avoiding weight gain, hypoglycemia risk
      and other adverse events, avoiding injections, convenience of dose
      administration, blood glucose monitoring, and cost of therapy. Patient feedback
      guided content revision. Treatment options were offered after presenting
      medication class risk-benefit information and eliciting patient values, goals,
      and preferences. The PDA received the highest International Patient Decision Aids
      Standards global score to date, 88/100, with 100% of criteria fully met for the
      following dimensions: development process, disclosures, evaluation process,
      evidence quality, guidance for users, information quality, language/readability,
      testing, and eliciting patient values. CONCLUSION: A PDA was developed to help
      T2DM patients make decisions regarding medication choice. This approach may be
      applicable to other chronic conditions.

PMID- 25995620
TI  - Body protective compound-157 enhances alkali-burn wound healing in vivo and
      promotes proliferation, migration, and angiogenesis in vitro.
AB  - Chemical burns take up a high proportion of burns admissions and can penetrate
      deep into tissues. Various reagents have been applied in the treatment of skin
      chemical burns; however, no optimal reagent for skin chemical burns currently
      exists. The present study investigated the effect of topical body protective
      compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat
      model. Topical treatment with BPC-157 was shown to accelerate wound closure
      following an alkali burn. Histological examination of skin sections with
      hematoxylin-eosin and Masson staining showed better granulation tissue formation,
      reepithelialization, dermal remodeling, and a higher extent of collagen
      deposition when compared to the model control group on the 18th day postwounding.
      BPC-157 could promote vascular endothelial growth factor expression in wounded
      skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide and cell cycle analysis demonstrated that BPC-157 enhanced the
      proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay
      and wound healing assay showed that BPC-157 significantly promoted migration of
      HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and
      accelerated vascular tube formation in vitro. Moreover, further studies suggested
      that BPC-157 regulated the phosphorylation level of extracellular signal
      regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c
      Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth,
      migration, and angiogenesis. Altogether, our results indicated that BPC-157
      treatment may accelerate wound healing in a model of alkali burn-induced skin
      injury. The therapeutic mechanism may be associated with accelerated granulation
      tissue formation, reepithelialization, dermal remodeling, and collagen deposition
      through ERK1/2 signaling pathway. 

PMID- 25995623
TI  - Improving access to shared decision-making for Hispanics/Latinos with
      inadequately controlled type 2 diabetes mellitus.
AB  - PURPOSE: To describe the cultural and linguistic adaptation and Spanish
      translation of an English-language patient decision aid (PDA) for use in
      supporting shared decision-making in Hispanics/Latinos with type 2 diabetes
      mellitus (T2DM), a group at a high risk for complications. PATIENTS AND METHODS:
      A steering committee of endocrinologists, a primary care physician, a certified
      diabetes educator, and a dietician, each with extensive experience in providing
      care to Hispanics/Latinos was convened to assess a PDA developed for English
      speaking patients with T2DM. English content was reviewed for cultural
      sensitivity and appropriateness for a Hispanic/Latino population. A consensus
      building process and iterative version edits incorporated clinician perspectives.
      The content was adapted to be consistent with traditional Hispanic/Latino
      cultural communication precepts (eg, avoidance of hostile confrontation; value
      for warm interaction; respect for authority; value of family support for
      decisions). The PDA was translated by native-speaking individuals with diabetes
      expertise. RESULTS: The PDA underwent testing during cognitive interviews with
      ten Spanish-speaking Hispanics/Latinos with T2DM to ensure that the content is
      reflective of the experience, understanding, and language Hispanic/Latino
      patients use to describe diabetes and treatment. Content edits were made to
      assure a literacy level appropriate to the audience, and the PDA was produced for
      online video dissemination. CONCLUSION: High-quality, well-developed tools to
      facilitate shared decision-making in populations with limited access to
      culturally sensitive information can narrow gaps and align care with individual
      patient preferences. A newly developed PDA is available for shared decision
      making that provides culturally appropriate treatment information for
      inadequately controlled Hispanics/Latinos with T2DM. The impact on the overall
      health of patients and care management of T2DM requires further study.

PMID- 25995624
TI  - Opinions of high school students in central Elazig about elderliness.
AB  - METHODS: Students attending five different types of high schools in central
      Elazig (a city in Turkey) during the 2009-2010 school year constitute the study
      population. One class was randomly selected from each high school. Out of 650
      students, 640 participated in the study. The data were evaluated by using the
      SPSS program; percentage, mean, and chi-square analyses were used. FINDINGS: Of
      all the students, 41.7% defined the elderly as those who are 60 years of age or
      older. When asked the question "What does elderliness mean to you?", the majority
      of the students, 27.2%, responded "peace and resting". The second most common
      answer, given by 23.6% of students, was "sickness/tiredness"; 16.6% responded
      "wisdom/experience". Many students (30.3%) stated that the most difficult thing
      about living with the elderly was their interference in everything; 30.6% of
      students stated that there was no difficulty at all. According to 42.7% of the
      students, the greatest problem that the elderly face is health. Of all of the
      students, 58.3% stated that they feared growing old. CONCLUSION: Our study has
      concluded the following: 1) High school students have a conventional perception
      of elderliness and 2) They embrace the elderly and think that perspectives on
      elderliness will change through education.

PMID- 25995625
TI  - Supported self-management for patients with COPD who have recently been
      discharged from hospital: a systematic review and meta-analysis.
AB  - PURPOSE: Although many hospitals promote self-management to chronic obstructive
      pulmonary disease (COPD) patients post discharge from hospital, the clinical
      effectiveness of this is unknown. We undertook a systematic review of the
      evidence as part of a Health Technology Assessment review. METHODS: A
      comprehensive search strategy with no language restrictions was conducted across
      relevant databases from inception to May 2012. Randomized controlled trials of
      patients with COPD, recently discharged from hospital after an acute exacerbation
      and comparing a self-management intervention with control, usual care or other
      intervention were included. Study selection, data extraction, and risk of bias
      assessment were undertaken by two reviewers independently. RESULTS: Of 13,559
      citations, 836 full texts were reviewed with nine randomized controlled trials
      finally included in quantitative syntheses. Interventions were heterogeneous.
      Five trials assessed highly supported multi-component interventions and four
      trials were less supported with fewer contacts with health care professionals and
      mainly home-based interventions. Total sample size was 1,466 (range 33-464 per
      trial) with length of follow-up 2-12 months. Trials varied in quality; poor
      patient follow-up and poor reporting was common. No evidence of effect in favor
      of self-management support was observed for all-cause mortality (pooled hazard
      ratio =1.07; 95% confidence interval [0.74 to 1.55]; I (2)=0.0%, [n=5 trials]).
      No clear evidence of effect on all-cause hospital admissions was observed (hazard
      ratio 0.88 [0.61, 1.27] I (2)=66.0%). Improvements in St George's Respiratory
      Questionnaire score were seen in favor of self-management interventions (mean
      difference =3.84 [1.29 to 6.40]; I (2)=14.6%), although patient follow-up rates
      were low. CONCLUSION: There is insufficient evidence to support self-management
      interventions post-discharge. There is a need for good quality primary research
      to identify effective approaches.

PMID- 25995626
TI  - Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and
      improves anticancer activity.
AB  - Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by
      its off-target cardiotoxicity. In the present study, we have developed physically
      stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs)
      that could sustainably release the drug, and studied its efficacy by in vitro
      anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl
      tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast
      cancer cells compared to the equivalent concentration of free imatinib mesylate.
      Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no
      significant cardiotoxicity or associated changes. Whereas, increased alanine
      aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels,
      and reduced white blood cell, red blood cell, and hemoglobin content were
      observed in the animals administered with free drug. While the histological
      sections from hearts of animals that received INPs did not show any significant
      cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic
      vacuolization were observed in the heart sections of animals administered with
      free imatinib mesylate. Based on these results, we conclude that nano
      encapsulation of imatinib mesylate increases its efficacy against cancer cells,
      with almost no cardiotoxicity. 

PMID- 25995627
TI  - Formation of curcumin nanoparticles via solution-enhanced dispersion by
      supercritical CO2.
AB  - In order to enhance the bioavailability of poorly water-soluble curcumin,
      solution-enhanced dispersion by supercritical carbon dioxide (CO2) (SEDS) was
      employed to prepare curcumin nanoparticles for the first time. A 2(4) full
      factorial experiment was designed to determine optimal processing parameters and
      their influence on the size of the curcumin nanoparticles. Particle size was
      demonstrated to increase with increased temperature or flow rate of the solution,
      or with decreased precipitation pressure, under processing conditions with
      different parameters considered. The single effect of the concentration of the
      solution on particle size was not significant. Curcumin nanoparticles with a
      spherical shape and the smallest mean particle size of 325 nm were obtained when
      the following optimal processing conditions were adopted: P = 20 MPa, T = 35
      degrees C, flow rate of solution = 0.5 mL.min(-1), concentration of solution =
      0.5%. Fourier transform infrared (FTIR) spectroscopy measurement revealed that
      the chemical composition of curcumin basically remained unchanged. Nevertheless,
      X-ray powder diffraction (XRPD) and thermal analysis indicated that the
      crystalline state of the original curcumin decreased after the SEDS process. The
      solubility and dissolution rate of the curcumin nanoparticles were found to be
      higher than that of the original curcumin powder (approximately 1.4 MUg/mL vs 0.2
      MUg/mL in 180 minutes). This study revealed that supercritical CO2 technologies
      had a great potential in fabricating nanoparticles and improving the
      bioavailability of poorly water-soluble drugs.

PMID- 25995628
TI  - Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate
      writers.
AB  - Research concerning the epigenome over the years has systematically and
      sequentially shown substantial development and we have moved from global
      inhibition of modifications of the epigenome toward identification and targeted
      therapy against tumor-specific epigenetic mechanisms. In accordance with this
      approach, several drugs with epigenetically modulating activity have received
      considerable attention and appreciation, and recently emerging scientific
      evidence is uncovering details of their mode of action. High-throughput
      technologies have considerably improved our existing understanding of tumor
      suppressors, oncogenes, and signaling pathways that are key drivers of cancer. In
      this review, we summarize the general epigenetic mechanisms in cancer, including:
      the post-translational modification of DNA methyltransferase and its mediated
      inactivation of Ras association domain family 1 isoform A, Sonic hedgehog
      signaling, Wnt signaling, Notch signaling, transforming growth factor signaling,
      and natural products with epigenetic modification ability. Moreover, we introduce
      the importance of nanomedicine for delivery of natural products with modulating
      ability to epigenetic machinery in cancer cells. Such in-depth and comprehensive
      knowledge regarding epigenetic dysregulation will be helpful in the upcoming era
      of molecular genomic pathology for both detection and treatment of cancer.
      Epigenetic information will also be helpful when nanotherapy is used for
      epigenetic modification. 

PMID- 25995629
TI  - Integration of nondegradable polystyrene and degradable gelatin in a core-sheath
      nanofibrous patch for pelvic reconstruction.
AB  - Pelvic organ prolapse (POP) is a serious health issue affecting many adult women.
      Complications of POP include pelvic pressure, pelvic pain, and problems in
      emptying their bowels or bladder. Sometimes, POP may even cause urinary outflow
      obstruction and lead to bladder or kidney infections. Currently, synthetic and
      naturally derived materials have been chosen for treatment of POP to reduce the
      high recurrence rates after surgical interventions. However, existing materials
      for POP treatment cannot meet the clinical requirements in terms of
      biocompatibility, mechanics, and minimal risk of rejection. Especially, erosion
      in synthetic polymers and rapid degradation in natural polymers limit their
      further applications in clinics. To address these concerns, we report a novel POP
      replacement using core-sheath polystyrene/gelatin electrospun nanofiber mesh. The
      outside gelatin sheath provides a hydrophilic surface and implantable integrity
      between host and guest, while the inner PS core offers the necessary mechanical
      support. The composite mesh shows graft accommodation in pelvic submucosa after
      implantation in vivo, as shown in hematoxylin-eosin staining and T helper cell
      phenotype and macrophage phenotype stainings. Qualitative analysis of inducible
      nitric oxide synthase, arginase, interferon-gamma, and interleukin-10 gene
      expressions also indicates that the implanted composite mesh switches to
      accommodation mode 2 weeks postimplantation. Thus, these novel core-sheath
      polystyrene/gelatin nanofibrous membranes are promising in pelvic reconstruction.

PMID- 25995630
TI  - Greener synthesis of electrospun collagen/hydroxyapatite composite fibers with an
      excellent microstructure for bone tissue engineering.
AB  - In bone tissue engineering, collagen/hydroxyapatite (HAP) fibrous composite
      obtained via electrospinning method has been demonstrated to support the cells'
      adhesion and bone regeneration. However, electrospinning of natural collagen
      often requires the use of cytotoxic organic solvents, and the HAP crystals were
      usually aggregated and randomly distributed within a fibrous matrix of collagen,
      limiting their clinical potential. Here, an effective and greener method for the
      preparation of collagen/HAP composite fibers was developed for the first time,
      and this green product not only had 40 times higher mechanical properties than
      that previously reported, but also had an excellent microstructure similar to
      that of natural bone. By dissolving type I collagen in environmentally friendly
      phosphate buffered saline/ethanol solution instead of the frequently-used
      cytotoxic organic solvents, followed with the key step of desalination, co
      electrospinning the collagen solution with the HAP sol, generates a collagen/HAP
      composite with a uniform and continuous fibrous morphology. Interestingly, the
      nano-HAP needles were found to preferentially orient along the longitudinal
      direction of the collagen fibers, which mimicked the nanostructure of natural
      bones. Based on the characterization of the related products, the formation
      mechanism for this novel phenomenon was proposed. After cross-linking with 1
      ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride/N
      hydroxysuccinimide, the obtained composite exhibited a significant enhancement in
      mechanical properties. In addition, the biocompatibility of the obtained
      composite fibers was evaluated by in vitro culture of the human myeloma cells (U2
      OS). Taken together, the process outlined herein provides an effective, non-toxic
      approach for the fabrication of collagen/HAP composite nanofibers that could be
      good candidates for bone tissue engineering. 

PMID- 25995631
TI  - Oxidative stress by layered double hydroxide nanoparticles via an SFK-JNK and p38
      NF-kappaB signaling pathway mediates induction of interleukin-6 and interleukin-8
      in human lung epithelial cells.
AB  - Anionic nanoclays are layered double hydroxide nanoparticles (LDH-NPs) that have
      been shown to exhibit toxicity by inducing reactive oxidative species and a
      proinflammatory mediator in human lung epithelial A549 cells. However, the
      molecular mechanism responsible for this LDH-NP-induced toxicity and the
      relationship between oxidative stress and inflammatory events remains unclear. In
      this study, we focused on intracellular signaling pathways and transcription
      factors induced in response to oxidative stress caused by exposure to LDH-NPs in
      A549 cells. Mitogen-activated protein kinase (MAPK) cascades, such as
      extracellular signal-regulated kinase, c-Jun-N-terminal kinase (JNK), and p38,
      were investigated as potential signaling mechanisms responsible for regulation of
      oxidative stress and cytokine release. Src family kinases (SFKs), which are known
      to mediate activation of MAPK, together with redox-sensitive transcription
      factors, including nuclear factor kappa B and nuclear factor-erythroid 2-related
      factor-2, were also investigated as downstream events of MAPK signaling. The
      results obtained suggest that LDH-NP exposure causes oxidative stress, leading to
      expression of antioxidant enzymes, such as catalase, glucose reductase,
      superoxide dismutase, and heme oxygenase-1, via a SFK-JNK and p38-nuclear factor
      kappa B signaling pathway. Further, activation of this signaling was also found
      to regulate release of inflammatory cytokines, including interleukin-6 and
      interleukin-8, demonstrating the inflammatory potential of LDH-NP. 

PMID- 25995633
TI  - The ability of streptomycin-loaded chitosan-coated magnetic nanocomposites to
      possess antimicrobial and antituberculosis activities.
AB  - Magnetic nanoparticles (MNPs) were synthesized by the coprecipitation of Fe(2+)
      and Fe(3+) iron salts in alkali media. MNPs were coated by chitosan (CS) to
      produce CS-MNPs. Streptomycin (Strep) was loaded onto the surface of CS-MNPs to
      form a Strep-CS-MNP nanocomposite. MNPs, CS-MNPs, and the nanocomposites were
      subsequently characterized using X-ray diffraction and were evaluated for their
      antibacterial activity. The antimicrobial activity of the as-synthesized
      nanoparticles was evaluated using different Gram-positive and Gram-negative
      bacteria, as well as Mycobacterium tuberculosis. For the first time, it was found
      that the nanoparticles showed antimicrobial activities against the tested
      microorganisms (albeit with a more pronounced effect against Gram-negative than
      Gram-positive bacteria), and thus, should be further studied as a novel nano
      antibiotic for numerous antimicrobial and antituberculosis applications.
      Moreover, since these nanoparticle bacteria fighters are magnetic, one can easily
      envision magnetic field direction of these nanoparticles to fight unwanted
      microorganism presence on demand. Due to the ability of magnetic nanoparticles to
      increase the sensitivity of imaging modalities (such as magnetic resonance
      imaging), these novel nanoparticles can also be used to diagnose the presence of
      such microorganisms. In summary, although requiring further investigation, this
      study introduces for the first time a new type of magnetic nanoparticle with
      microorganism theranostic properties as a potential tool to both diagnose and
      treat diverse microbial and tuberculosis infections. 

PMID- 25995635
TI  - Hydroxypropyl-beta-cyclodextrin functionalized calcium carbonate microparticles
      as a potential carrier for enhancing oral delivery of water-insoluble drugs.
AB  - The objective of the present study was to demonstrate that a novel hydroxypropyl
      beta-cyclodextrin functionalized calcium carbonate (HP-beta-CD/CC) based
      amorphous solid dispersion (ASD) can be used to increase the solubility and oral
      bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a
      model compound and loaded into the nanoporous HP-beta-CD/CC matrix using an
      immersion method. The IRB-loaded HP-beta-CD/CC formulation was characterized by
      various analytical techniques, such as specific surface area analysis, scanning
      electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray
      diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with
      PXRD and DSC confirmed that IRB was fully converted into the amorphous form in
      the nanopores of HP-beta-CD/CC. From the solubility and dissolution tests, it was
      observed that the aqueous solubility and dissolution rate of IRB-loaded HP-beta
      CD/CC were increased significantly compared with those of pure IRB and IRB-loaded
      mesoporous silica. Likewise, the IRB-loaded HP-beta-CD/CC formulation exhibited
      better absorption compared with that of the commercially available IRB capsules
      in beagle dogs. The mean peak plasma concentration (C max) and the area under the
      mean plasma concentration-time curve (AUC[0->48]) of IRB-loaded HP-beta-CD/CC
      were 1.56- and 1.52-fold higher than that of the commercial product,
      respectively. Furthermore, the IRB-loaded HP-beta-CD/CC formulation exhibited
      excellent stability against re-crystallization. These results clearly demonstrate
      that HP-beta-CD/CC based porous ASD is a promising formulation approach to
      improve the aqueous solubility and the in vivo absorption performance of a water
      insoluble compound like IRB. 

PMID- 25995634
TI  - Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified
      Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib
      and gambogic acid in RPMI-8226 cells.
AB  - The purpose of this study was to determine the potential benefits of combination
      therapy using dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic
      nanoparticles (MNPs) combined with nontoxic concentration of bortezomib (BTZ) and
      gambogic acid (GA) on multiple myeloma (MM) RPMI-8226 cells and possible
      underlying mechanisms. The effects of BTZ-GA-loaded MNP-Fe3O4 (BTZ-GA/MNPs) on
      cell proliferation were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,4,
      diphenyltetrazolium bromide (MTT) method. Cell cycle and apoptosis were detected
      using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP
      nick-end labeling (TUNEL) assay and flow cytometry (FCM). Furthermore, DMSA-Fe3O4
      MNPs were characterized in terms of distribution, apoptotic morphology, and
      cellular uptake by transmission electron microscopy (TEM) and 4,6-diamidino-2
      phenylindole (DAPI) staining. Subsequently, the effect of BTZ-GA/MNPs combination
      on PI3K/Akt activation and apoptotic-related protein were appraised by Western
      blotting. MTT assay and hematoxylin and eosin (HE) staining were applied to
      elevate the functions of BTZ-GA/MNPs combination on the tumor xenograft model and
      tumor necrosis. The results of this study revealed that the majority of MNPs were
      quasi-spherical and the MNPs taken up by cells were located in the endosome
      vesicles of cytoplasm. Nontoxic concentration of BTZ-GA/MNPs increased G2/M phase
      cell cycle arrest and induced apoptosis in RPMI-8226 cells. Furthermore, the
      combination of BTZ-GA/MNPs activated phosphorylated Akt levels, Caspase-3, and
      Bax expression, and down-regulated the PI3K and Bcl-2 levels significantly.
      Meanwhile, the in vivo tumor xenograft model indicated that the treatment of BTZ
      GA/MNPs decreased the tumor growth and volume and induced cell apoptosis and
      necrosis. These findings suggest that chemotherapeutic agents polymerized MNPs
      Fe3O4 with GA could serve as a better alternative for targeted therapeutic
      approaches to treat multiple myeloma. 

PMID- 25995636
TI  - The clinical utility of lurasidone in schizophrenia: patient considerations.
AB  - Lurasidone is a novel antipsychotic agent approved for the treatment of
      schizophrenia in a number of countries including the United Kingdom, other
      European countries, the United States, and Canada. In addition to full antagonist
      activity at the dopamine D2 (Ki, 1 nM) and serotonin 5-HT2A (Ki, 0.5 nM)
      receptors, the pharmacodynamic profile of lurasidone is notable for its high
      affinity for serotonin 5-HT7 receptors (0.5 nM) and its partial agonist activity
      at 5-HT1A receptors (Ki, 6.4 nM). Long-term treatment of schizophrenia with
      lurasidone has been shown to reduce the risk of relapse in patients with
      schizophrenia. Lurasidone appears to be associated with minimal effects on body
      weight, and low risk for clinically meaningful alterations in glucose, lipids, or
      electrocardiography parameters. Evidence from two randomized trials also suggests
      improvement in functional capacity and cognitive functioning in people with
      schizophrenia. A significant evidence base supports the use of lurasidone as a
      promising agent for the treatment of schizophrenia. 

PMID- 25995632
TI  - Targeted delivery of brain-derived neurotrophic factor for the treatment of
      blindness and deafness.
AB  - Neurodegenerative causes of blindness and deafness possess a major challenge in
      their clinical management as proper treatment guidelines have not yet been found.
      Brain-derived neurotrophic factor (BDNF) has been established as a promising
      therapy against neurodegenerative disorders including hearing and visual loss.
      Unfortunately, the blood-retinal barrier and blood-cochlear barrier, which have a
      comparable structure to the blood-brain barrier prevent molecules of larger sizes
      (such as BDNF) from exiting the circulation and reaching the targeted cells.
      Anatomical features of the eye and ear allow use of local administration,
      bypassing histo-hematic barriers. This paper focuses on highlighting a variety of
      strategies proposed for the local administration of the BDNF, like direct
      delivery, viral gene therapy, and cell-based therapy, which have been shown to
      successfully improve development, survival, and function of spiral and retinal
      ganglion cells. The similarities and controversies for BDNF treatment of
      posterior eye diseases and inner ear diseases have been analyzed and compared. In
      this review, we also focus on the possibility of translation of this knowledge
      into clinical practice. And finally, we suggest that using nanoparticulate drug
      delivery systems may substantially contribute to the development of clinically
      viable techniques for BDNF delivery into the cochlea or posterior eye segment,
      which, ultimately, can lead to a long-term or permanent rescue of auditory and
      optic neurons from degeneration. 

PMID- 25995637
TI  - In patients suffering from idiopathic central serous chorioretinopathy, anxiety
      scores are higher than in healthy controls, but do not vary according to sex or
      repeated central serous chorioretinopathy.
AB  - INTRODUCTION: Idiopathic central serous chorioretinopathy (CSCR) is a relatively
      common ophthalmic disorder characterized by the development of a serous
      detachment of the sensory retina. Psychophysiological factors may trigger or
      maintain CSCR, though, surprisingly, the association between CSCR and anxiety has
      yet to be studied. The aims of the present study were threefold: to determine
      whether 1) Iranian patients with CSCR have higher scores for anxiety, 2) anxiety
      is lower, if CSCR has been experienced twice, and whether 3) anxiety scores
      differ between sexes. METHODS: A total of 30 patients with CSCR and 30 healthy
      age-and sex-matched controls took part in the study. A brief face-to-face
      interview was conducted covering demographic variables and history and occurrence
      of CSCR and assessing anxiety. RESULTS: Compared to healthy controls, anxiety was
      significantly higher in both first-time and second-time CSCR patients. In CSCR
      patients, anxiety scores did not differ between sexes. CONCLUSION: Higher anxiety
      scores were observed in Iranian patients with CSCR, irrespective of whether this
      was the first or second occurrence of CSCR. This suggests there is no
      psychological adaptation in terms of reduced anxiety among patients with repeated
      CSCR.

PMID- 25995638
TI  - Evaluating depressive symptoms in mania: a naturalistic study of patients with
      bipolar disorder.
AB  - OBJECTIVE: This study aimed to evaluate patients with bipolar I disorder (BD-I)
      who have mania with depressive symptoms and who meet the new "with mixed
      features" specifier of the Diagnostic and Statistical Manual of Mental Disorders,
      fifth edition (DSM-5). METHOD: This prospective, multinational, naturalistic
      study surveyed psychiatrists and their patients with BD-I from October 2013 to
      March 2014. Eligible patients had BD-I, had a (current) manic episode, and had
      experienced onset of a manic episode within the previous 3 months. Psychiatrists
      provided patient information on depressive symptoms (DSM-5 criteria); symptoms of
      anxiety, irritability, and agitation; suicide attempts; and physician
      satisfaction with treatment response. Data were stratified according to whether
      patients met the criteria for the BD-I "with mixed features" specifier of DSM-5
      (>=3 depressive symptoms) or not, and characteristics were compared between the
      two subgroups. Patients also self-reported on depressive symptoms using the Mini
      International Neuropsychiatric Interview module questionnaire. RESULTS: Overall,
      34% of 1,035 patients met the criteria for BD-I "with mixed features," exhibiting
      >=3 depressive symptoms during their current manic episode. This correlated with
      the matched patient self-reports of depressive symptoms. During their current
      manic episode, BD-I patients "with mixed features" had more severe symptoms of
      anxiety, irritability, and agitation (average composite severity score of 4.1 vs
      3.4), a higher incidence of suicide attempts (38% vs 9%), and more physician
      dissatisfaction with treatment response (22% vs 14%), compared to patients with 0
      2 depressive symptoms (all P<0.05). CONCLUSION: This study found that patients
      with BD-I "with mixed features" (ie, >=3 depressive symptoms during a manic
      episode), suffered, on average, from a greater burden of disease than patients
      with pure mania. Improved identification of these patients may help to optimize
      treatment outcomes.

PMID- 25995639
TI  - Depressive disorders co-existing with Addison-Biermer anemia - case report.
AB  - BACKGROUND: Anemia is a disease that can co-exist with depression, other mental
      disorders, or somatic diseases. Anemia can imitate symptoms of depression, while
      depression symptoms can mask concurring symptoms of anemia. CASE PRESENTATION: I
      am presenting a case of a 48-year-old woman with Addison-Biermer anemia, with co
      existing mood disorders. The clinical analysis of the presented patient's history
      indicates diagnostic problems and a need for a detailed analysis of drug-related
      complications that occurred during previous treatment, eg, in the form of
      neuroleptic malignant syndrome. CONCLUSION: The presented case report contains
      valuable guidelines that can be of assistance in diagnostics and treatment of
      patients treated for mental disorders, who are also diagnosed with somatic
      diseases.

PMID- 25995640
TI  - Association of diabetes-related distress, depression, medication adherence, and
      health-related quality of life with glycated hemoglobin, blood pressure, and
      lipids in adult patients with type 2 diabetes: a cross-sectional study.
AB  - This study examined the associations of diabetes-related distress (DRD),
      depressive symptoms, health-related quality of life (HRQoL), and medication
      adherence with glycemia, blood pressure (BP), and lipid biomarkers in adults with
      type 2 diabetes mellitus (T2D). This cross-sectional study was conducted in three
      Malaysian public health clinics in 2012-2013, recruited adult patients (aged >=30
      years) with T2D who had been diagnosed for more than one year, were on active
      follow-up, and had recent blood test results. Univariable and multivariable
      analyses were performed to identify significant associated factors for glycated
      hemoglobin (HbA1c) BP, and lipids. The response rate was 93.1% (700/752). The
      majority were females (52.8%), Malay (52.4%), and married (78.7%). DRD correlated
      with systolic BP (r= -0.16); depressive symptoms correlated with low-density
      lipoprotein cholesterol (r=0.12) and total cholesterol (r=0.13); medication
      adherence correlated with HbA1c (r= -0.14) and low-density lipoprotein
      cholesterol (r= -0.11); and HRQoL correlated with casual blood glucose (r= 
      0.11), high-density lipoprotein cholesterol (r= -0.13), and total cholesterol (r=
      -0.08). Multivariable analyses showed that HRQoL was significantly associated
      with casual blood glucose (adjusted B= -0.06, P=0.024); DRD was associated with
      systolic BP (adjusted B= -0.08, P=0.066); depressive symptoms were associated
      with low-density lipoprotein cholesterol (adjusted B=0.02, P=0.061), and
      medication adherence was associated with HbA1c (adjusted B= -0.11, P=0.082) and
      total cholesterol (adjusted B= -0.06, P=0.086). There were significant and
      distinctive associations of DRD, depressive symptoms, HRQoL, and medication
      adherence with glycemia, BP, and lipid biomarkers. Unexpected beneficial
      therapeutic effects of DRD on BP require further study. A multidisciplinary
      approach may be needed for risk management in adults with T2D at the primary care
      level. 

PMID- 25995641
TI  - Serous macular detachment, yellow macular deposits, and prominent middle limiting
      membrane in multiple myeloma.
AB  - Bone marrow-derived multiple myeloma is a type of plasma cell tumor that may be
      associated with ocular complications. A 52-year-old male patient was admitted to
      our eye clinic with the complaint of sudden visual loss and a visual acuity of
      20/50 in the right eye and 20/800 in the left eye. Fundus examination revealed
      common flame-shaped hemorrhages, venous dilatation and tortuosity, Roth spots,
      serous macular detachment, and yellow macular deposits in both eyes. Evaluation
      with fundus fluorescein angiography, fundus autofluorescence, and spectral-domain
      optical coherence tomography resulted in suspicion of hyperviscosity retinopathy
      and referral to the hematology clinic. After hematology consultation confirmed a
      diagnosis of multiple myeloma, chemotherapy and plasmapheresis were initiated.
      Four months after presentation, best-corrected visual acuity was 20/20 in both
      eyes and improvement in hyperviscosity retinopathy, serous macular detachment,
      and yellow macular deposits was observed. 

PMID- 25995642
TI  - Practical use of sevelamer in chronic kidney disease patients on dialysis in
      People's Republic of China.
AB  - Hyperphosphatemia is a common complication of dialysis patients. Only 38.5% of
      Chinese dialysis patients met the Kidney Disease Outcomes Quality Initiative
      defined targets for serum phosphate. Sevelamer is a high molecular weight
      cationic hydrogel polymer that prevents absorption of dietary phosphate by
      binding it in the gastrointestinal tract. In Chinese trials, it was confirmed
      that sevelamer had better efficacy than calcium carbonate in terms of reducing
      the serum level of phosphorus and calcium-phosphate product. Sevelamer can also
      reduce the levels of lipid parameters and improve the micro-inflammatory state.
      When sevelamer was combined with other treatments, it elicited superior effects
      on calcium phosphorus metabolism, secondary hyperparathyroidism, and renal
      osteodystrophy. Combination treatment of sevelamer and traditional Chinese
      medicine has the unique advantage. However, sevelamer is associated with a high
      incidence of gastrointestinal adverse effects in Chinese patients. Although more
      effective, the practical use of sevelamer is not very common because it is
      expensive and not paid by medical insurance. This article provides a
      comprehensive review of the practical use of sevelamer in chronic kidney disease
      patients on dialysis in People's Republic of China. 

PMID- 25995643
TI  - GSTM1 null genotype and gastric cancer risk in the Chinese population: an updated
      meta-analysis and review.
AB  - Although a number of studies have been conducted on the association between the
      GSTM1 null genotype and gastric cancer in People's Republic of China, this
      association remains elusive and controversial. To clarify the effects of the
      GSTM1 null genotype on the risk of gastric cancer, an updated meta-analysis was
      performed in the Chinese population. Related studies were identified from PubMed,
      Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese
      National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up
      to November 5, 2014. A total of 25 studies including 3,491 cases and 5,921
      controls were included in this meta-analysis. Overall, a significant association
      (odds ratio [OR] =1.47, 95% CI: 1.28-1.69) was found between the null GSTM1 and
      gastric cancer risk when all studies in Chinese population were pooled into the
      meta-analysis. In subgroup analyses stratified by quality score, geographic area,
      and source of controls, the same results were observed. Additionally, a
      significant association was found both in smokers and non-smokers. This meta
      analysis showed that the null GSTM1 may be a potential biomarker for gastric
      cancer risk in Chinese, and further studies with gene-gene and gene-environment
      interactions are required for definite conclusions. 

PMID- 25995644
TI  - SIRT1 expression is associated with poor prognosis of lung adenocarcinoma.
AB  - Several studies have reported that the overexpression of Sirtuin 1 (SIRT1) was
      associated with poor prognosis in various human cancers. However, little is known
      regarding the prognostic value of SIRT1 in lung adenocarcinoma. Therefore, the
      aim of this study is to evaluate the role of SIRT1 in the prognosis of lung
      adenocarcinoma patients. Using a tissue microarray, we detected SIRT1 expression
      by immunohistochemistry in lung adenocarcinoma tissue, as well as in
      corresponding noncancerous tissues (NCTs). A high expression level of SIRT1 was
      observed in 74.7% (56/75) of patients with lung adenocarcinoma and 6.7% (5/75) of
      NCTs (P<0.001). SIRT1 expression was significantly associated with high
      pathological stage. Importantly, we found that SIRT1 expression was associated
      with worse overall survival in these lung adenocarcinoma patients (67.0 months vs
      104.5 months; P=0.005). In addition, anaplastic lymphoma kinase, epidermal growth
      factor receptor, vascular endothelial growth factor (VEGF), and Survivin
      expression were evaluated by fluorescent in situ hybridization or
      immunohistochemistry, respectively. We found that VEGF and Survivin were both
      highly expressed in the lung adenocarcinoma tissues, as compared to NCTs.
      Moreover, the SIRT1 and VEGF expression statuses were significantly positively
      correlated (r=0.238, P=0.039), while SIRT1 and Survivin expression status were
      not significantly correlated (r=0.220, P=0.058). Correlation analysis showed a
      positive correlation between VEGF and Survivin expression (r=0.436, P<0.001).
      However, we found that VEGF and Survivin expression were not associated with the
      prognosis of lung adenocarcinoma patients (P=0.334; P=0.433, respectively). Taken
      together, our findings suggest that SIRT1 plays a role in the progression of lung
      adenocarcinoma and may be a significant prognostic indicator for lung
      adenocarcinoma patients. 

PMID- 25995645
TI  - Impact of beta-blockers on prostate cancer mortality: a meta-analysis of 16,825
      patients.
AB  - INTRODUCTION: Increasing evidence suggests that beta-blocker use might be
      associated with reduced mortality in prostate cancer patients. To provide a
      quantitative assessment of this association, we pooled data available to examine
      the association between beta-blocker use and mortality of prostate cancer.
      METHODS: We identified studies by a literature search of MEDLINE (from 1 January
      1966) and EMBASE (from 1 January 1974), through 10 September 2014, and by
      searching the reference lists of pertinent articles. Two authors independently
      screened and reviewed the eligibility of each study. The primary outcomes were
      prostate cancer-specific mortality and all-cause mortality. RESULTS: A total of
      four studies including 16,825 patients were included in this meta-analysis.
      Analysis of all studies showed that beta-blocker use was associated with reduced
      prostate cancer-specific mortality (hazard ratio =0.85, 95% confidence interval
      =0.77-0.94), without any heterogeneity between studies (Q=3.59, I2=16.5%,
      P=0.309). However, we observed no association with all-cause mortality (hazard
      ratio =0.97, 95% confidence interval =0.90-1.04). There was also no evidence of
      the presence of significant heterogeneity between the four studies (Q=2.48,
      I2=0.0%, P=0.480). CONCLUSION: These findings indicate that beta-blocker use was
      associated with reduced cancer-specific mortality among prostate cancer patients
      taking beta-blockers.

PMID- 25995646
TI  - Discrepancy in MALDI-TOF MS identification of uncommon Gram-negative bacteria
      from lower respiratory secretions in patients with cystic fibrosis.
AB  - INTRODUCTION: Early identification of microbial organisms from respiratory
      secretions of patients with cystic fibrosis (CF) is important to guide
      therapeutic decisions. The objective was to compare the accuracy of matrix
      assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF
      MS) relative to the conventional phenotypic method in identifying common
      bacterial isolates, including nonfermenting Gram-negative bacteria, in a cohort
      of patients with CF. METHODS: A total of 123 isolates from 50 patients with CF
      representing 14 bacterial species from respiratory specimens were identified
      using MALDI-TOF MS in parallel with conventional phenotypic methods.
      Discrepancies were confirmed by 16S ribosomal RNA (rRNA) gene sequencing in five
      Gram-negative isolates. RESULTS: The MALDI-TOF MS managed to identify 122/123
      (99.2%) bacterial isolates to the genus level and 118/123 (95.9%) were identified
      to the species level. The MALDI-TOF MS results were 100% consistent to the
      species level with conventional phenotypic identification for isolates of
      Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae,
      Streptococcus pyogenes, Achromobacter xylosoxidans, Stenotrophomonas maltophilia,
      and other uncommon organisms such as Chryseobacterium gleum and Enterobacter
      cloacae. The 5/123 (4.6%) isolates misidentified were all Gram-negative bacteria.
      The isolation of E. cloacae and Haemophilus paraphrohaemolyticus may extend the
      potentially pathogenic list of organisms isolated from patients with CF.
      CONCLUSION: Although the technique provides an early identification and
      antimicrobial therapy approach in patients with CF, limitation in the diagnosis
      of uncommon Gram-negative bacteria may exist.

PMID- 25995647
TI  - Health-related quality of life in type 1 and type 2 diabetic patients in a
      Portuguese central public hospital.
AB  - BACKGROUND: Diabetes mellitus is a chronic metabolic disease, the prevalence of
      which has registered a considerable increase, mainly in adults and elderly. The
      purpose of this study was to assess the relationship between health-related
      quality of life in patients with diabetes and sex, body mass index, type of
      diabetes and treatment regimens (type 1 diabetes: intensive versus conventional
      treatment; type 2 diabetes: insulin use versus non-insulin use), and duration of
      diabetes. METHODS: One hundred and twenty-four patients with diabetes were
      interviewed. Health-related quality of life was evaluated using the age-adjusted
      Short-Form 36 dimensions (physical functioning, role-physical, bodily pain,
      general health, vitality, social functioning, role-emotional, and mental health),
      and related to demographic and clinical variables. Independent samples t-tests
      and One-Way Analysis of Variance were used to compare means of independent
      samples. The degree of association between pairs of variables was measured by
      Pearson's (r) or Spearman's (rs ) correlation coefficients. RESULTS: The mean age
      of the study population was 55.7+/-16.4 years; 54.8% were male, and 77.4% had
      type 2 diabetes. Females reported worse quality of life than males in all
      dimensions of the Short-Form 36, except for role-physical and bodily pain. Obese
      patients had worse physical functioning than normal weight and overweight
      patients, and worse vitality than their normal weight counterparts. Type 2
      diabetic patients taking insulin had lower physical functioning and vitality than
      those without insulin therapy. Longer duration of diabetes was associated with
      lower physical functioning, role-physical, general health, vitality, role
      emotional, and mental health. CONCLUSION: Being female, obese, having type 2
      diabetes and taking insulin, and having a longer disease duration are
      characteristics associated with worse age-adjusted quality of life in patients
      with diabetes.

PMID- 25995648
TI  - Priority interventions to improve the management of chronic non-cancer pain in
      primary care: a participatory research of the ACCORD program.
AB  - PURPOSE: There is evidence that the management of chronic non-cancer pain (CNCP)
      in primary care is far from being optimal. A 1-day workshop was held to explore
      the perceptions of key actors regarding the challenges and priority interventions
      to improve CNCP management in primary care. METHODS: Using the Chronic Care Model
      as a conceptual framework, physicians (n=6), pharmacists (n=6), nurses (n=6),
      physiotherapists (n=6), psychologists (n=6), pain specialists (n=6), patients
      (n=3), family members (n=3), decision makers and managers (n=4), and pain
      researchers (n=7) took part in seven focus groups and five nominal groups.
      RESULTS: Challenges identified in focus group discussions were related to five
      dimensions: knowledge gap, "work in silos", lack of awareness that CNCP
      represents an important clinical problem, difficulties in access to health
      professionals and services, and patient empowerment needs. Based on the nominal
      group discussions, the following priority interventions were identified:
      interdisciplinary continuing education, interdisciplinary treatment approach,
      regional expert leadership, creation and definition of care paths, and patient
      education programs. CONCLUSION: Barriers to optimal management of CNCP in primary
      care are numerous. Improving its management cannot be envisioned without
      considering multifaceted interventions targeting several dimensions of the
      Chronic Care Model and focusing on both clinicians and patients.

PMID- 25995649
TI  - Long-term survival in advanced melanoma patients using repeated therapies:
      successive immunomodulation improving the odds?
AB  - BACKGROUND: Patients with advanced metastatic melanoma are often confronted with
      little prospect of medium- to longer-term survival by any currently available
      therapeutic means. However, most clinicians are aware of exceptional cases where
      survival defies the notion of futility. Prolonged survival from immunotherapies,
      including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen
      4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role
      for immune system modulation. We aimed to identify cases where exceptional
      survival from advanced melanoma occurred prior to recent novel therapies to
      facilitate better understanding of this phenomenon. METHODS: Cases of long-term
      survival of >=3 years' duration (from diagnosis of metastatic disease) were
      identified from the database of one clinician; these cases were treated before
      the availability of newer immunotherapies, and they were documented and examined.
      A literature search for reported outcome measures from published studies using
      older and recent therapies for advanced melanoma was conducted to enable the
      comparison of data. RESULTS: Eighteen cases were identified that identified
      survival of >=3 years' duration from metastatic disease (12 American Joint
      Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These
      were assessed and reported to detail the clinical course. Standard clinical
      prognostication methods predicted high risk of early mortality in those patients.
      No identifiable differences could be detected between these and other patients
      with similar patterns of disease. At evaluation, 17 patients (94%) had survived
      >=5 years, and eleven patients (61%) had survived >=10 years (range: 3-15 years).
      The median survival duration with metastatic disease was 11 years; 15 remained
      alive and three had died. Published studies of melanoma therapies were tabled for
      comparison. CONCLUSION: The fact that 18 cases of exceptional survival in
      advanced melanoma were identified is remarkable in itself. Even with recent
      therapies, the factors for improved survival remain enigmatic; however, one
      apparent common denominator in most cases was the persistent use of repeated
      therapies to reduce tumor bulk, induce tumor necrosis, and/or cause
      immunostimulation. These cases are instructive, suggesting manipulation of an
      established, endogenous, existing immune response. These observations provide
      practical evidence that the course for any patient with advanced melanoma at the
      outset should be considered unpredictable, open to immunomanipulation, and thus
      not uniformly fatal. The findings were compared and interpreted with reported
      newer immunotherapeutic approaches.

PMID- 25995650
TI  - Outcomes for women admitted to a mother and baby unit: a systematic review.
AB  - Mother and baby units (MBUs) provide inpatient psychiatric care for mothers and
      their infants up to a year after childbirth. They are commissioned to support the
      mother-infant relationship as well as stabilize maternal mental health. As their
      efficacy at meeting these aims had not previously been systematically assessed,
      this paper reviewed the international literature relating to psychological
      outcomes following MBU admission. A systematic search of five databases
      identified 23 papers eligible for inclusion, reporting on a range of outcomes
      indicating positive effects on maternal mental health and the mother-infant
      relationship and an absence of adverse effects on child development. The review
      also highlighted specific groups responding less favorably to MBU admission, eg,
      mothers with a diagnosis of schizophrenia. Although the included studies were of
      variable methodological quality, the research findings consistently indicated
      positive effects. Implications for research and clinical practice are outlined in
      the discussion. 

PMID- 25995651
TI  - Opana((r)) ER induced thrombotic thrombocytopenic purpura.
AB  - We present the case of a patient who developed thrombotic thrombocytopenic
      purpura (TTP) following intravenous injection of Opana((r)) ER. TTP reemerged
      after three months of abstinence with Opana misuse. This case report brings
      awareness to the possibility of developing TTP in those who misuse Opana, which
      is a growing concern. 

PMID- 25995652
TI  - Improving patient safety after rigid bronchoscopy in adults: laryngeal mask
      airway versus face mask - a pilot study.
AB  - BACKGROUND: There are still no clear guidelines in the literature on per
      procedural bronchoscopic management for anesthesiologists, and few relevant
      datasets are available. To obtain rapid recovery from anesthesia, it is often
      necessary to keep patients in the recovery room for several hours until they
      become clinically stable. In this study, we tested the hypothesis that the
      laryngeal mask airway (LMA) enables better respiratory and hemodynamic recovery
      than the oxygen face mask (FM) in patients undergoing rigid bronchoscopy.
      METHODS: Twenty-one patients undergoing elective bronchoscopy of the upper airway
      were randomized to ventilation assistance with FM or LMA after a rigid
      bronchoscopy procedure under general anesthesia. The primary endpoint was
      duration of post-surgical recovery and the secondary endpoints were postoperative
      hemodynamic and respiratory parameters. Assessment of the study endpoints was
      performed by an intensive care specialist blinded to the method of ventilation
      used. The statistical analysis was performed using the Fisher's Exact test for
      nominal data and the Student's t-test for continuous data. RESULTS: There was no
      statistically significant difference in post-procedural time between the two
      groups (P=0.972). The recovery parameters were significantly better in the LMA
      group than in the FM group, with significantly fewer desaturation, hypotensive,
      and bradycardic events (P<0.05). CONCLUSION: We conclude that the LMA may be
      safer and more comfortable than the FM in patients undergoing rigid bronchoscopy.

PMID- 25995653
TI  - Effects of training and anthropometric factors on marathon and 100 km
      ultramarathon race performance.
AB  - BACKGROUND: Marathon (42 km) and 100 km ultramarathon races are increasing in
      popularity. The aim of the present study was to investigate the potential
      associations of anthropometric and training variables with performance in these
      long-distance running competitions. METHODS: Training and anthropometric data
      from a large cohort of marathoners and 100 km ultramarathoners provided the basis
      of this work. Correlations between training and anthropometric indices of
      subjects and race performance were assessed using bivariate and multiple
      regression analyses. RESULTS: A combination of volume and intensity in training
      was found to be suitable for prediction of marathon and 100 km ultramarathon race
      pace. The relative role played by these two variables was different, in that
      training volume was more important than training pace for the prediction of 100
      km ultramarathon performance, while the opposite was found for marathon
      performance. Anthropometric characteristics in terms of body fat percentage
      negatively affected 42 km and 100 km race performance. However, when this factor
      was relatively low (ie, less than 15% body fat), the performance of 42 km and 100
      km races could be predicted solely on the basis of training indices. CONCLUSION:
      Mean weekly training distance run and mean training pace were key predictor
      variables for both marathon and 100 km ultramarathon race performance. Predictive
      correlations for race performance are provided for runners with a relatively low
      body fat percentage.

PMID- 25995655
TI  - Planning and guidance of cardiac resynchronization therapy-lead implantation by
      evaluating coronary venous anatomy assessed with multidetector computed
      tomography.
AB  - OBJECTIVES: We sought to evaluate the utility of multidetector computed
      tomography (MDCT) in preoperative planning of cardiac resynchronization therapy
      (CRT) device implantation. BACKGROUND: Variation in coronary venous anatomy can
      affect optimal lead placement and may warrant preimplantation visualization prior
      to CRT lead placement. METHODS: Prospective randomized enrollment of 29 patients
      (17 males; mean age at implant 66.7 +/- 12.8 years) was undertaken. Patients were
      randomized to preimplantation MDCT (GE((r)) 64-detector Lightspeed, n = 16) or no
      MDCT. Implantation was planned based on three-dimensional coronary venous
      reconstruction as visualized in the CT group. Measurement of coronary sinus (CS)
      angulation, CS ostial (os) diameter, right atrial (RA) width, volume, and height
      was undertaken prior to implant. Intraoperative CS lead implantation times
      (introduction, cannulation, and left ventricular [LV] lead positioning),
      procedure time, fluoroscopy time, and venogram contrast volume were measured to
      determine if there was a difference between patients who underwent preimplant CT
      scan and those who did not. RESULTS: CS os diameter (mean = 13.8 +/- 2.9 cm) was
      inversely correlated with total fluoroscopy time (r = -0.57, P = .008), and total
      procedure time, but this correlation was not statistically significant (r = 
      0.36, P = 0.12). RA width (mean = 52.8 +/- 9.9 cm) was associated with a shorter
      total procedure time (r = -0.44, P = .047) and LV lead positioning time (r = 
      0.33, P = .012). There were no statistically significant differences between the
      CT group and the non-CT group with respect to total intraoperative and
      fluoroscopy times or venogram contrast volumes. Total procedure time was longer
      in the CT group but the difference was not statistically significant (94 +/- 27.2
      vs. 74.7 +/- 26.6; P = .065). CONCLUSION: Noninvasive visualization of the
      coronary venous anatomy before CRT implantation can be used as a guide for lead
      placement. While no significant differences were noted between the two groups
      with respect to intraoperative variables, CS os diameter and RA width inversely
      correlated to a shorter procedure time and LV lead positioning time,
      respectively. Further clinical trials regarding the utility of MDCT to visualize
      coronary venous anatomy prior to CRT implantation for procedural planning and
      lead placement guidance are warranted.

PMID- 25995656
TI  - Applying Expectancy Theory to residency training: proposing opportunities to
      understand resident motivation and enhance residency training.
AB  - Medical resident education in the United States has been a matter of national
      priority for decades, exemplified initially through the Liaison Committee for
      Graduate Medical Education and then superseded by the Accreditation Council for
      Graduate Medical Education. A recent Special Report in the New England Journal of
      Medicine, however, has described resident educational programs to date as
      prescriptive, noting an absence of innovation in education. Current aims of
      contemporary medical resident education are thus being directed at ensuring
      quality in learning as well as in patient care. Achievement and work-motivation
      theories attempt to explain people's choice, performance, and persistence in
      tasks. Expectancy Theory as one such theory was reviewed in detail, appearing
      particularly applicable to surgical residency training. Correlations between
      Expectancy Theory as a work-motivation theory and residency education were
      explored. Understanding achievement and work-motivation theories affords an
      opportunity to gain insight into resident motivation in training. The application
      of Expectancy Theory in particular provides an innovative perspective into
      residency education. Afforded are opportunities to promote the development of
      programmatic methods facilitating surgical resident motivation in education. 

PMID- 25995657
TI  - Recent trends in diagnostic techniques for inflammatory bowel disease.
AB  - Although ileocolonoscopy is the gold standard for diagnosis of inflammatory bowel
      disease and is useful for assessing the disease severity in the colon and
      terminal ileum, several alternative diagnostic techniques have been developed
      recently. For ulcerative colitis (UC), magnification colonoscopy, endocytoscopy,
      and confocal laser endomicroscopy enable assessment of histological inflammation
      without the need for biopsy. Capsule endoscopy is useful for detection of small
      intestinal and colonic lesions in both female and male patients. For UC, capsule
      endoscopy may be useful for evaluating colonic inflammation in patients with a
      previous poor colonoscopy experience, while it should be used only in Crohn's
      disease (CD) patients with unexplained symptoms when other examinations are
      negative. Magnetic resonance enterography (MRE) is particularly useful for
      detecting transmural inflammation, stenosis, and extraintestinal lesions,
      including abscesses and fistulas. MRE is also useful when evaluating small and
      large intestinal lesions, even in cases with severe strictures in which full
      evaluation of the small bowel would be virtually impossible using other devices.
      Therefore, the appropriate diagnostic devices for detecting CD lesions in the
      small and large intestine should be used. 

PMID- 25995654
TI  - A selective review of glutamate pharmacological therapy in obsessive-compulsive
      and related disorders.
AB  - Glutamate, an excitatory central nervous system neurotransmitter, is emerging as
      a potential alternative pharmacological treatment when compared to gamma
      aminobutyric acid (GABA)-, dopamine-, and serotonin-modulating treatments for
      neuropsychiatric conditions. The pathophysiology, animal models, and clinical
      trials of glutamate modulation are explored in disorders with underlying
      inhibitory deficits (cognitive, motor, behavioral) including obsessive-compulsive
      disorder, attention deficit hyperactivity disorder, Tourette syndrome,
      trichotillomania, excoriation disorder, and nail biting. Obsessive-compulsive
      disorder, attention deficit hyperactivity disorder, and grooming disorders
      (trichotillomania and excoriation disorder) have emerging positive data, although
      only scarce controlled trials are available. The evidence is less supportive for
      the use of glutamate modulators in Tourette syndrome. Glutamate-modulating agents
      show promise in the treatment of disorders of inhibition. 

PMID- 25995658
TI  - Hard tissue regeneration using bone substitutes: an update on innovations in
      materials.
AB  - Bone is a unique organ composed of mineralized hard tissue, unlike any other body
      part. The unique manner in which bone can constantly undergo self-remodeling has
      created interesting clinical approaches to the healing of damaged bone. Healing
      of large bone defects is achieved using implant materials that gradually
      integrate with the body after healing is completed. Such strategies require a
      multidisciplinary approach by material scientists, biological scientists, and
      clinicians. Development of materials for bone healing and exploration of the
      interactions thereof with the body are active research areas. In this review, we
      explore ongoing developments in the creation of materials for regenerating hard
      tissues. 

PMID- 25995659
TI  - Clinical implications of copy number variations in autoimmune disorders.
AB  - Human genetic variation is represented by the genetic differences both within and
      among populations, and most genetic variants do not cause overt diseases but
      contribute to disease susceptibility and influence drug response. During the last
      century, various genetic variants, such as copy number variations (CNVs), have
      been associated with diverse human disorders. Here, we review studies on the
      associations between CNVs and autoimmune diseases to gain some insight. First,
      some CNV loci are commonly implicated in various autoimmune diseases, such as
      Fcgamma receptors in patients with systemic lupus erythemoatosus or idiopathic
      thrombocytopenic purpura and beta-defensin genes in patients with psoriasis or
      Crohn's disease. This means that when a CNV locus is associated with a particular
      autoimmune disease, we should examine its potential associations with other
      diseases. Second, interpopulation or interethnic differences in the effects of
      CNVs on phenotypes exist, including disease susceptibility, and evidence suggests
      that CNVs are important to understand susceptibility to and pathogenesis of
      autoimmune diseases. However, many findings need to be replicated in independent
      populations and different ethnic groups. The validity and reliability of
      detecting CNVs will improve quickly as genotyping technology advances, which will
      support the required replication. 

PMID- 25995660
TI  - Neutrophil gelatinase-associated lipocalin as a predictor of adverse renal
      outcomes in immunoglobulin A nephropathy.

PMID- 25995661
TI  - Use of (18)F-FDG PET to predict tumor progression and survival in patients with
      intermediate hepatocellular carcinoma treated by transarterial chemoembolization.
AB  - BACKGROUND/AIMS: (18)F-Fluorodeoxyglucose positron-emission tomography ((18)F-FDG
      PET) has been used to assess the biological behavior of hepatocellular carcinoma
      (HCC). In this study, we investigated the usefulness of (18)F-FDG PET for
      predicting tumor progression and survival in patients with intermediate Barcelona
      Clinic Liver Cancer (BCLC) intermediate-stage HCC treated by transarterial
      chemoembolization (TACE). METHODS: From February 2006 to March 2013, 210 patients
      treated with TACE, including 77 patients with BCLC intermediate-stage HCC,
      underwent examination by (18)F-FDG PET. (18)F-FDG uptake was calculated based on
      the tumor maximum (Tmax) standardized uptake value (SUV), the liver mean (Lmean)
      SUV, and the ratio of the Tmax SUV to the Lmean SUV (Tmax/Lmean). RESULTS: The
      mean follow-up period for the 77 patients (52 males, 25 females; average age,
      63.3 years) was 22.2 months. The median time to progression of HCC in patients
      with a low Tmax/Lmean (< 1.83) and high Tmax/Lmean (>= 1.83) was 17 and 6 months,
      respectively (p < 0.001). The median overall survival time of patients with a low
      and high Tmax/Lmean was 44 and 14 months, respectively (p = 0.003). Multivariate
      analysis revealed that the Tmax/Lmean was an independent predictor of overall
      survival (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.210 to 3.156;
      p = 0.006) and tumor progression (HR, 2.05; 95% CI, 1.264 to 3.308; p = 0.004).
      CONCLUSIONS: (18)F-FDG uptake calculated by the Tmax/Lmean using PET predicted
      tumor progression and survival in patients with BCLC intermediate-stage HCC
      treated by TACE.

PMID- 25995662
TI  - The relationship between serum asymmetric dimethylarginine levels and subjective
      sleep quality in normotensive patients with type 2 diabetes mellitus.
AB  - BACKGROUND/AIMS: Poor sleep quality (SQ) is associated with increased
      cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine
      (ADMA) is an independent predictor of cardiovascular mortality and morbidity.
      However, no sufficient data regarding the relationship between ADMA levels and SQ
      have been reported. The goal of the current study was to evaluate the association
      between SQ and ADMA levels in normotensive patients with type 2 diabetes
      mellitus. METHODS: The study participants consisted of 78 normotensive type 2
      diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep
      Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor
      sleepers." Factors associated with poor SQ were analyzed using a multiple
      regression model. Serum ADMA levels were measured using high performance liquid
      chromatography. RESULTS: The median ADMA levels of the poor sleepers were
      increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs.
      4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was
      decreased in poor sleepers (p < 0.01). Global PSQI scores were positively
      correlated with ADMA levels (p < 0.01) and negatively correlated with the L
      arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p
      < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that
      ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p
      = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were
      associated with poor SQ independently of glomerular filtration rate, sex, age,
      duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood
      pressure. CONCLUSIONS: Self-reported SQ was independently associated with ADMA
      levels in normotensive patients with diabetes mellitus.

PMID- 25995663
TI  - Drug-resistance pattern of Mycobacterium tuberculosis strains from patients with
      pulmonary and extrapulmonary tuberculosis during 2006 to 2013 in a Korean
      tertiary medical center.
AB  - BACKGROUND/AIMS: We evaluated the trend in the rates of drug-resistant
      tuberculosis (TB) over time, as well as the difference in the drug-resistance
      pattern between pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis
      (EPTB) at a private referral center in South Korea. METHODS: All patients with
      culture-confirmed TB from 2006 to 2013 were included. RESULTS: In total, 1,745
      patients were included: 1,431 (82.0%) were new cases, and 314 (18.0%) were cases
      treated previously; 1,610 (92.3%) were diagnosed with PTB, and 135 (7.7%) were
      diagnosed with EPTB. Multidrug-resistant (MDR) and extensively drug-resistant
      (XDR) TB were detected in 5.8% and 2.0% of new cases and in 20.1% and 8.6% of
      previously treated cases, respectively. The MDR TB rate during the study period
      decreased remarkably, whereas the MDR and XDR TB rates decreased significantly in
      previously treated cases. No difference in the drug-resistance rate was detected
      between PTB and EPTB. CONCLUSIONS: The TB drug-resistance rate, particularly that
      of MDR TB, remained high at a private referral hospital, and the drug-resistance
      rate did not decrease significantly from 2006 to 2013. This finding underscores
      the need for a national survey regarding the prevalence of drug-resistant TB to
      obtain the most accurate and current drug-resistance status in South Korea,
      including the private sector.

PMID- 25995664
TI  - Reference interval for thyrotropin in a ultrasonography screened Korean
      population.
AB  - BACKGROUND/AIMS: The diagnostic accuracy of thyroid dysfunctions is primarily
      affected by the validity of the reference interval for serum thyroid-stimulating
      hormone (TSH). Thus, the present study aimed to establish a reference interval
      for TSH using a normal Korean population. METHODS: This study included 19,465
      subjects who were recruited after undergoing routine health check-ups. Subjects
      with overt thyroid disease, a prior history of thyroid disease, or a family
      history of thyroid cancer were excluded from the present analyses. The reference
      range for serum TSH was evaluated in a normal Korean reference population which
      was defined according to criteria based on the guidelines of the National Academy
      of Clinical Biochemistry, ultrasound (US) findings, and smoking status. Sex and
      age were also taken into consideration when evaluating the distribution of serum
      TSH levels in different groups. RESULTS: In the presence of positive anti-thyroid
      peroxidase antibodies or abnormal US findings, the central 95 percentile interval
      of the serum TSH levels was widened. Additionally, the distribution of serum TSH
      levels shifted toward lower values in the current smokers group. The reference
      interval for TSH obtained using a normal Korean reference population was 0.73 to
      7.06 mIU/L. The serum TSH levels were higher in females than in males in all
      groups, and there were no age-dependent shifts. CONCLUSIONS: The present findings
      demonstrate that the serum TSH reference interval in a normal Korean reference
      population was higher than that in other countries. This result suggests that the
      upper and lower limits of the TSH reference interval, which was previously
      defined by studies from Western countries, should be raised for Korean
      populations.

PMID- 25995665
TI  - Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of
      adverse renal outcomes in immunoglobulin A nephropathy.
AB  - BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well
      known biomarker of acute kidney injury. We evaluated the value of plasma NGAL
      (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy
      (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center
      were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent
      assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney
      disease (CKD) stage 3 or above at the last follow-up. Pearson correlation
      coefficient and Cox regression were used for analyses. RESULTS: The mean age of
      all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged
      between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age
      (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular
      filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and
      the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up
      period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a
      multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95%
      confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR,
      5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003
      to 1.022; p = 0.013) were independent predictors associated with adverse renal
      outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical
      prognostic factors and was also an independent predictor of adverse renal
      outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while
      further studies are needed to confirm the clinical value.

PMID- 25995666
TI  - High serum and urine neutrophil gelatinase-associated lipocalin levels are
      independent predictors of renal progression in patients with immunoglobulin A
      nephropathy.
AB  - BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the
      progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase
      associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We
      investigated whether serum or urine NGAL predicts prognosis in patients with
      IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from
      January 2005 to December 2010, whose serum and urine samples at the time of
      kidney biopsy were preserved by freezing. We retrospectively reviewed patient
      clinical data and followed patients until October 2012. Serum and urine NGAL
      levels were measured using an enzyme-linked immunosorbent assay kit. Renal
      progression was defined as an estimated glomerular filtration rate decline by >
      50% or progression to end-stage renal disease. RESULTS: There were 121 patients
      enrolled in this study. During the median follow-up period of 41.49 months, renal
      progression was found in nine patients (7.4%). Serum or urine NGAL alone could
      not predict renal progression; however, when serum and urine NGAL levels were
      combined, belonging to the high NGAL group independently predicted renal
      progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to
      21.73; p = 0.014), along with tubular damage graded according to the Oxford
      classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a
      Kaplan-Meier curve of renal survival showed significantly higher renal
      progression in patients in the high NGAL group (log rank, p = 0.004).
      CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time
      of kidney biopsy predict renal progression.

PMID- 25995667
TI  - Role of frontline autologous stem cell transplantation in young, high-risk
      diffuse large B-cell lymphoma patients.
AB  - BACKGROUND/AIMS: Several studies have demonstrated the effect of autologous
      hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for
      patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role
      of auto-HSCT as a frontline treatment has not been fully investigated in the
      rituximab era. We validated the age-adjusted International Prognostic Index
      (aaIPI) score for high-risk DLBCL patients and identified a possible role for
      frontline auto-HSCT. METHODS: We recommended frontline auto-HSCT for high-risk
      DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III
      to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an
      aaIPI score >= 2. From 2006 to 2011, among the 150 DLBCL patients aged <= 60
      years who were treated with six cycles of rituximab plus cyclophosphamide,
      doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a
      complete response (CR) were treated with auto-HSCT. For comparison, we selected
      35 well-matched high-risk patients with CR who completed R-CHOP treatment alone.
      In addition, there were 81 low-risk patients and 11 refractory patients. RESULTS:
      DLBCL patients with an aaIPI score >= 2 showed inferior overall survival (OS; p =
      0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score
      0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the
      clinical parameters were not different. The high-risk group treated with
      frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in
      the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004),
      but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone.
      CONCLUSIONS: We identified the possible role of frontline auto-HSCT for high-risk
      DLBCL with a higher stage (III to IV) and elevated LDH level.

PMID- 25995668
TI  - A comparison of the clinical characteristics of elderly and non-elderly women
      with community-onset, non-obstructive acute pyelonephritis.
AB  - BACKGROUND/AIMS: Acute pyelonephritis (APN) is the most common cause of community
      onset bacteremia in hospitalized elderly patients. The objectives of this study
      were to investigate the differences in the clinical and microbiological data of
      hospitalized elderly and non-elderly women with community-onset APN. METHODS:
      Women with community-onset APN as a discharge diagnosis were identified from
      January 2004 to December 2013 using an electronic medical records system. We
      compared the clinical and microbiologic data in elderly and non-elderly women
      with community-onset APN due to Enterobacteriaceae. RESULTS: Of the 1,134 women
      with community-onset APN caused by Enterobacteriaceae, 443 were elderly and 691
      were non-elderly women. The elderly group had a lower frequency of upper and
      lower urinary tract symptoms/signs than the non-elderly. The incidence of
      bacteremia, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae,
      patients with a C-reactive protein (CRP) level >= 15 mg/dL, and patients with a
      leukocyte count >= 15,000/mm(3) in the blood, were significantly higher in the
      elderly group than in the non-elderly group. The proportion of patients requiring
      hospitalization for 10 days or more was significantly higher in the elderly group
      compared to the non-elderly group (51.5% vs. 26.2%, p < 0.001). The clinical cure
      rates at 4 to 14 days after the end of therapy were 98.3% (338/344) and 97.4%
      (519/533) in the elderly and non-elderly groups, respectively (p = 0.393).
      CONCLUSIONS: Elderly women with APN exhibit higher serum CRP levels, a higher
      frequency of bacteremia, a higher proportion of ESBL-producing uropathogens, and
      require a longer hospitalization than non-elderly women, although these patients
      may not complain of typical urinary symptoms.

PMID- 25995669
TI  - Sleep quality in rheumatoid arthritis, and its association with disease activity
      in a Korean population.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the sleep quality between
      rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the
      relationship between RA disease activity and sleep quality in Korea. METHODS: A
      total of 130 RA patients and 67 age- and sex-matched healthy controls were
      enrolled in a comparative study of sleep quality using the Pittsburgh Sleep
      Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte
      sedimentation rate, serum C-reactive protein, Beck Depression Inventory second
      edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog
      scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep
      quality of RA patients according to the disease activity (DAS28 <= 3.2, 3.2 <
      DAS28 < 5.1, and DAS28 >= 5.1, respectively). RESULTS: The total PSQI score and
      the frequency of poor sleep quality, were higher in the RA patients (5.62 +/-
      4.19, 38.5%) than in the control subjects (3.57 +/- 2.17, 13.4%). The patients
      with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS
      score than the patients without sleep disturbance (PSQI <= 5). The score in
      subjective sleep quality, sleep latency, sleep duration, habitual sleep
      efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of
      poor sleep quality were increased when RA activity was high. CONCLUSIONS: Sleep
      disturbance was observed in RA patients (38.5%), and high RA disease activity was
      associated with poor sleep quality in Korea.

PMID- 25995670
TI  - Predictive factors of radiographic progression in ankylosing spondylitis.
AB  - BACKGROUND/AIMS: The course of ankylosing spondylitis (AS) is rather variable,
      and the factors that predict radiographic progression remain largely obscure. In
      this study, we tried to determine the clinical factors and laboratory measures
      that are useful in predicting the radiographic progression of patients with AS.
      METHODS: In 64 consecutive patients with AS, we collected radiographic and
      laboratory data over 3 years. Radiographic data included images of the sacroiliac
      (SI) and hip joints and laboratory data included areas under the curve (AUC) of
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alkaline
      phosphatase (ALP), and hemoglobin (Hb). We investigated associations among
      changes in radiographic scores, initial clinical manifestations and laboratory
      measurements. RESULTS: Changes in scores for the SI joint and lumbar spine did
      not correlate with AUC for ESR, CRP, or ALP. AUC for Hb did not significantly
      correlate with radiographic progression in any joint. Patients with hip arthritis
      at the initial visit showed significantly higher radiographic score changes after
      3 years in the SI and hip joint compared to those without hip arthritis. Patients
      who had shoulder arthritis as the initial manifestation had significantly
      increased AUCs for ESR and CRP compared to those without shoulder arthritis.
      However, at 3 years, the change of the lumbar spine score was significantly
      higher in patients without shoulder arthritis. CONCLUSIONS: These results
      indicate that hip arthritis at presentation is a useful clinical marker for
      predicting the structural damage to the SI and hip joint, and suggest that
      initial shoulder arthritis correlates with slower radiographic progression of the
      lumbar spine.

PMID- 25995671
TI  - Pancreatic mucinous cystadenoma of borderline malignancy associated with
      Clonorchis sinensis.

PMID- 25995672
TI  - Cutaneous vasculitis and renal involvement in Mycoplasma pneumoniae infection.

PMID- 25995673
TI  - Henoch-Schonlein purpura secondary to infective endocarditis in a patient with
      pulmonary valve stenosis and a ventricular septal defect.

PMID- 25995674
TI  - Triple-negative breast cancer that progressed as estrogen receptor-positive skin
      metastases.

PMID- 25995675
TI  - Polymyalgia rheumatica following paraspinal muscle inflammation and sacroiliitis.

PMID- 25995676
TI  - Homonymous hemianopia in a patient with Behcet's disease.

PMID- 25995677
TI  - Purple urine bag syndrome in a patient with a urethral balloon catheter and a
      history of ileal conduit urinary diversion.

PMID- 25995678
TI  - Erratum: Intrathoracic kidney with left-sided Bochdalek hernia in a woman with
      bacteremic acute pyelonephritis due to Escherichia coli.

PMID- 25995679
TI  - MRI features of hepatocellular carcinoma related to biologic behavior.
AB  - Imaging studies including magnetic resonance imaging (MRI) play a crucial role in
      the diagnosis and staging of hepatocellular carcinoma (HCC). Several recent
      studies reveal a large number of MRI features related to the prognosis of HCC. In
      this review, we discuss various MRI features of HCC and their implications for
      the diagnosis and prognosis as imaging biomarkers. As a whole, the favorable MRI
      findings of HCC are small size, encapsulation, intralesional fat, high apparent
      diffusion coefficient (ADC) value, and smooth margins or hyperintensity on the
      hepatobiliary phase of gadoxetic acid-enhanced MRI. Unfavorable findings include
      large size, multifocality, low ADC value, non-smooth margins or hypointensity on
      hepatobiliary phase images. MRI findings are potential imaging biomarkers in
      patients with HCC. 

PMID- 25995681
TI  - Preoperative estimation of future remnant liver function following portal vein
      embolization using relative enhancement on gadoxetic acid disodium-enhanced
      magnetic resonance imaging.
AB  - OBJECTIVE: To retrospectively evaluate relative enhancement (RE) in the
      hepatobiliary phase of gadoxetic acid disodium-enhanced magnetic resonance (MR)
      imaging as a preoperative estimation of future remnant liver (FRL) function in a
      patients who underwent portal vein embolization (PVE). MATERIALS AND METHODS: In
      53 patients, the correlation between the indocyanine green clearance (ICG-K) and
      RE imaging was analyzed before hepatectomy (first analysis). Twenty-three of the
      53 patients underwent PVE followed by a repeat RE imaging and ICG test before an
      extended hepatectomy and their results were further analyzed (second analysis).
      Whole liver function and FRL function were calculated on the MR imaging as
      follows: RE x total liver volume (RE Index) and FRL-RE x FRL volume (Rem RE
      Index), respectively. Regarding clinical outcome, posthepatectomy liver failure
      (PHLF) was evaluated in patients undergoing PVE. RESULTS: Indocyanine green
      clearance correlated with the RE Index (r = 0.365, p = 0.007), and ICG-K of FRL
      (ICG-Krem) strongly correlated with the Rem RE Index (r = 0.738, p < 0.001) in
      the first analysis. Both the ICG-Krem and the Rem RE Index were significantly
      correlated after PVE (r = 0.508, p = 0.013) at the second analysis. The rate of
      improvement of the Rem RE Index from before PVE to after PVE was significantly
      higher than that of ICG-Krem (p = 0.014). Patients with PHLF had a significantly
      lower Rem RE Index than patients without PHLF (p = 0.023). CONCLUSION: Relative
      enhancement imaging can be used to estimate FRL function after PVE.

PMID- 25995682
TI  - Combined Use of Automatic Tube Voltage Selection and Current Modulation with
      Iterative Reconstruction for CT Evaluation of Small Hypervascular Hepatocellular
      Carcinomas: Effect on Lesion Conspicuity and Image Quality.
AB  - OBJECTIVE: To assess the lesion conspicuity and image quality in CT evaluation of
      small (<= 3 cm) hepatocellular carcinomas (HCCs) using automatic tube voltage
      selection (ATVS) and automatic tube current modulation (ATCM) with or without
      iterative reconstruction. MATERIALS AND METHODS: One hundred and five patients
      with 123 HCC lesions were included. Fifty-seven patients were scanned using both
      ATVS and ATCM and images were reconstructed using either filtered back-projection
      (FBP) (group A1) or sinogram-affirmed iterative reconstruction (SAFIRE) (group
      A2). Forty-eight patients were imaged using only ATCM, with a fixed tube
      potential of 120 kVp and FBP reconstruction (group B). Quantitative parameters
      (image noise in Hounsfield unit and contrast-to-noise ratio of the aorta, the
      liver, and the hepatic tumors) and qualitative visual parameters (image noise,
      overall image quality, and lesion conspicuity as graded on a 5-point scale) were
      compared among the groups. RESULTS: Group A2 scanned with the automatically
      chosen 80 kVp and 100 kVp tube voltages ranked the best in lesion conspicuity and
      subjective and objective image quality (p values ranging from < 0.001 to 0.004)
      among the three groups, except for overall image quality between group A2 and
      group B (p = 0.022). Group A1 showed higher image noise (p = 0.005) but similar
      lesion conspicuity and overall image quality as compared with group B. The
      radiation dose in group A was 19% lower than that in group B (p = 0.022).
      CONCLUSION: CT scanning with combined use of ATVS and ATCM and image
      reconstruction with SAFIRE algorithm provides higher lesion conspicuity and
      better image quality for evaluating small hepatic HCCs with radiation dose
      reduction.

PMID- 25995683
TI  - Diagnostic Performance of CT Angiography in Patients Visiting Emergency
      Department with Overt Gastrointestinal Bleeding.
AB  - OBJECTIVE: To investigate the diagnostic performance of computed tomography
      angiography (CTA) in identifying the cause of bleeding and to determine the
      clinical features associated with a positive test result of CTA in patients
      visiting emergency department with overt gastrointestinal (GI) bleeding.
      MATERIALS AND METHODS: We included 111 consecutive patients (61 men and 50 women;
      mean age: 63.4 years; range: 28-89 years) who visited emergency department with
      overt GI bleeding. They underwent CTA as a first-line diagnostic modality from
      July through December 2010. Two radiologists retrospectively reviewed the CTA
      images and determined the presence of any definite or potential bleeding focus by
      consensus. An independent assessor determined the cause of bleeding based on
      other diagnostic studies and/or clinical follow-up. The diagnostic performance of
      CTA and clinical characteristics associated with positive CTA results were
      analyzed. RESULTS: To identify a definite or potential bleeding focus, the
      diagnostic yield of CTA was 61.3% (68 of 111). The overall sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value were
      84.8% (67 of 79), 96.9% (31 of 32), 98.5% (67 of 68), and 72.1% (31 of 43),
      respectively. Positive CTA results were associated with the presence of massive
      bleeding (p = 0.001, odds ratio: 11.506). CONCLUSION: Computed tomography
      angiography as a first-line diagnostic modality in patients presenting with overt
      GI bleeding showed a fairly high accuracy. It could identify definite or
      potential bleeding focus with a moderate diagnostic yield and a high PPV. CTA is
      particularly useful in patients with massive bleeding.

PMID- 25995684
TI  - Physiological and Functional Magnetic Resonance Imaging Using Balanced Steady
      state Free Precession.
AB  - Balanced steady-state free precession (bSSFP) is a highly efficient pulse
      sequence that is known to provide the highest signal-to-noise ratio per unit
      time. Recently, bSSFP is getting increasingly popular in both the research and
      clinical communities. This review will be focusing on the application of the
      bSSFP technique in the context of probing the physiological and functional
      information. In the first part of this review, the basic principles of bSSFP are
      briefly covered. Afterwards, recent developments related to the application of
      bSSFP, in terms of physiological and functional imaging, are introduced and
      reviewed. Despite its long development history, bSSFP is still a promising
      technique that has many potential benefits for obtaining high-resolution
      physiological and functional images. 

PMID- 25995685
TI  - Inter-observer variation in ultrasound measurement of the volume and diameter of
      thyroid nodules.
AB  - OBJECTIVE: Thyroid nodule measurement using ultrasonography (US) is widely
      performed in various clinical scenarios. The purpose of this study was to
      evaluate inter-observer variation in US measurement of the volume and maximum
      diameter of thyroid nodules. MATERIALS AND METHODS: This retrospective study
      included 73 consecutive patients with 85 well-defined thyroid nodules greater
      than 1 cm in their maximum diameter. US examinations were independently performed
      by using standardized measurement methods, conducted by two clinically
      experienced thyroid radiologists. The maximum nodule diameter and nodule volume,
      calculated from nodule diameters using the ellipsoid formula, were obtained by
      each reader. Inter-observer variations in volume and maximum diameter were
      determined using 95% Bland-Altman limits of agreement. The degree of inter
      observer variations in volumes and the maximum diameters were compared using the
      Student's t test, between nodules < 2 cm in maximum diameter and those with >= 2
      cm. RESULTS: The mean inter-observer difference in measuring the nodule volume
      was -1.6%, in terms of percentage of the nodule volume, and the 95% limit of
      agreement was +/- 13.1%. For maximum nodule diameter, the mean inter-observer
      difference was -0.6%, in terms of percentage of the nodule diameter, and the 95%
      limit of agreement was +/- 7.3%. Inter-observer variation in volume was greater
      in nodules of < 2 cm in maximum diameter, compared to the larger nodules (p =
      0.035). However, no statistically significant difference was noted between the
      two groups regarding maximum nodule diameters (p = 0.511). CONCLUSION: Any
      differences smaller than 13.1% and 7.3% in volume and maximum diameter,
      respectively, measured by using US for well-defined thyroid nodules of > 1 cm
      should not be considered as a real change in size.

PMID- 25995686
TI  - Computed tomography and magnetic resonance imaging findings of nasal cavity
      hemangiomas according to histological type.
AB  - OBJECTIVE: To compare computed tomography (CT) and magnetic resonance imaging
      (MRI) findings between two histological types of nasal hemangiomas (cavernous
      hemangioma and capillary or lobular capillary hemangioma). MATERIALS AND METHODS:
      CT (n = 20; six pre-contrast; 20 post-enhancement) and MRI (n = 7) images from 23
      patients (16 men and seven women; mean age, 43 years; range, 13-73 years) with a
      pathologically diagnosed nasal cavity hemangioma (17 capillary and lobular
      capillary hemangiomas and six cavernous hemangiomas) were reviewed, focusing on
      lesion location, size, origin, contour, enhancement pattern, attenuation or
      signal intensity (SI), and bony changes. RESULTS: The 17 capillary and lobular
      hemangiomas averaged 13 mm (range, 4-37 mm) in size, and most (n = 13) were
      round. Fourteen capillary hemangiomas had marked or moderate early phase
      enhancement on CT, which dissipated during the delayed phase. Four capillary
      hemangiomas on MRI showed marked enhancement. Bony changes were usually not seen
      on CT or MRI (seen on five cases, 29.4%). Half of the lesions (2/4) had low SI on
      T1-weighted MRI images and heterogeneously high SI with signal voids on T2
      weighted images. The six cavernous hemangiomas were larger than the capillary
      type (mean, 20.5 mm; range, 10-39 mm) and most had lobulating contours (n = 4),
      with characteristic enhancement patterns (three centripetal and three multifocal
      nodular), bony remodeling (n = 4, 66.7%), and mild to moderate heterogeneous
      enhancement during the early and delayed phases. CONCLUSION: CT and MRI findings
      are different between the two histological types of nasal hemangiomas,
      particularly in the enhancement pattern and size, which can assist in
      preoperative diagnosis and planning of surgical tumor excision.

PMID- 25995687
TI  - Evaluation of engraftment of superparamagnetic iron oxide-labeled mesenchymal
      stem cells using three-dimensional reconstruction of magnetic resonance imaging
      in photothrombotic cerebral infarction models of rats.
AB  - OBJECTIVE: To evaluate engraftment by visualizing the location of human bone
      marrow-derived mesenchymal stem cells (hBM-MSCs) three-dimensionally in
      photothrombotic cerebral infarction (PTCI) models of rats. MATERIALS AND METHODS:
      Magnetic resonance imaging (MRI) of an agarose block containing superparamagnetic
      iron oxide (SPIO)-labeled hBM-MSCs was performed using a 3.0-T MRI, T2-(T2WI),
      T2(*)-(T2(*)WI), and susceptibility-weighted images (SWI). PTCI was induced in 6
      rats, and 2.5 * 10(5) SPIO-labeled hBM-MSCs were infused through the ipsilateral
      internal carotid artery (ICA group) or tail vein (IV group). MRI was performed on
      days 1, 3, 7, and 14 after stem cell injection. Dark signal regions were
      confirmed using histology. Three-dimensional MRI reconstruction was performed
      using the clinical workflow solution to evaluate the engraftment of hBM-MSCs.
      Volumetric analysis of the engraftment was also performed. RESULTS: The volumes
      of SPIO-labeled hBM-MSCs in the phantom MRI were 129.3, 68.4, and 25.9 uL using
      SWI, T2(*)WI, and T2WI, respectively. SPIO-labeled hBM-MSCs appeared on day 1
      after injection, encircling the cerebral infarction from the ventral side. Dark
      signal regions matched iron positive cells and human origin (positive) cells. The
      volume of the engraftment was larger in the ICA group on days 1, 3, and 7, after
      stem cell injection (p < 0.05 on SWI). SWI was the most sensitive MRI pulse
      sequence (p < 0.05). The volume of infarction decreased until day 14. CONCLUSION:
      The engraftment of SPIO-labeled hBM-MSCs can be visualized and evaluated three
      dimensionally in PTCI models of rats. The engraftment volume was larger in the
      ICA group than IV group on early stage within one week.

PMID- 25995688
TI  - Percutaneous unilateral biliary metallic stent placement in patients with
      malignant obstruction of the biliary hila and contralateral portal vein steno
      occlusion.
AB  - OBJECTIVE: To investigate the outcomes of percutaneous unilateral metallic stent
      placement in patients with a malignant obstruction of the biliary hila and a
      contralateral portal vein steno-occlusion. MATERIALS AND METHODS: Sixty patients
      with a malignant hilar obstruction and unilobar portal vein steno-occlusion
      caused by tumor invasion or preoperative portal vein embolization were enrolled
      in this retrospective study from October 2010 to October 2013. All patients were
      treated with percutaneous placement of a biliary metallic stent, including
      expanded polytetrafluoroethylene (ePTFE)-covered stents in 27 patients and
      uncovered stents in 33 patients. RESULTS: A total of 70 stents were successfully
      placed in 60 patients. Procedural-related minor complications, including self
      limiting hemobilia (n = 2) and cholangitis (n = 4) occurred in six (10%)
      patients. Acute cholecystitis occurred in two patients. Successful internal
      drainage was achieved in 54 (90%) of the 60 patients. According to a Kaplan-Meier
      analysis, median survival time was 210 days (95% confidence interval [CI], 135
      284 days), and median stent patency time was 133 days (95% CI, 94-171 days). No
      significant difference in stent patency was observed between covered and
      uncovered stents (p = 0.646). Stent dysfunction occurred in 16 (29.6%) of 54
      patients after a mean of 159 days (range, 65-321 days). CONCLUSION: Unilateral
      placement of ePTFE-covered and uncovered stents in the hepatic lobe with a patent
      portal vein is a safe and effective method for palliative treatment of patients
      with a contralateral portal vein steno-occlusion caused by an advanced hilar
      malignancy or portal vein embolization. No significant difference in stent
      patency was detected between covered and uncovered metallic stents.

PMID- 25995680
TI  - 2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice
      guideline for the management of hepatocellular carcinoma.
AB  - The guideline for the management of hepatocellular carcinoma (HCC) was first
      developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and
      the National Cancer Center, Korea. Since then, many studies on HCC have been
      carried out in Korea and other countries. In particular, a substantial body of
      knowledge has been accumulated on diagnosis, staging, and treatment specific to
      Asian characteristics, especially Koreans, prompting the proposal of new
      strategies. Accordingly, the new guideline presented herein was developed on the
      basis of recent evidence and expert opinions. The primary targets of this
      guideline are patients with suspicious or newly diagnosed HCC. This guideline
      provides recommendations for the initial treatment of patients with newly
      diagnosed HCC. 

PMID- 25995689
TI  - Interventional radiological treatment of renal transplant complications: a
      pictorial review.
AB  - Renal transplantation is the treatment of choice for patients with chronic renal
      failure, which produces a dramatic improvement in the quality of life and
      survival rates, in comparison to long-term dialysis. Nowadays, new imaging
      modalities allow early diagnosis of complications, and thanks to the recent
      developments of interventional techniques, surgery may be avoided in most cases.
      Knowledge in the types of renal transplant complications is fundamental for a
      correct pre-operative planning. In this article, we described the most common or
      clinically relevant renal transplant complications and explained their
      interventional management. 

PMID- 25995690
TI  - Cervical interlaminar epidural steroid injection for unilateral cervical
      radiculopathy: comparison of midline and paramedian approaches for efficacy.
AB  - OBJECTIVE: The objective of this study was to compare the clinical outcomes of
      the cervical interlaminar epidural steroid injection (CIESI) for unilateral
      radiculopathy by the midline or paramedian approaches and to determine the
      prognostic factors of CIESI. MATERIALS AND METHODS: We retrospectively analyzed
      182 patients who underwent CIESI from January 2009 to December 2012. Inclusion
      criteria were no previous spinal steroid injection, presence of a cross-sectional
      image, and presence of follow-up records. Exclusion criteria were patients with
      bilateral cervical radiculopathy and/or dominant cervical axial pain, combined
      peripheral neuropathy, and previous cervical spine surgery. Short-term clinical
      outcomes were evaluated at the first follow-up after CIESI. We compared the
      clinical outcomes between the midline and paramedian approaches. Possible
      prognostic factors for the outcome, such as age, gender, duration of
      radiculopathy, and cause of radiculopathy were also analyzed. RESULTS: Cervical
      interlaminar epidural steroid injections were effective in 124 of 182 patients
      (68.1%) at the first follow-up. There was no significant difference in the
      clinical outcomes of CIESI, between midline (69.6%) and paramedian (63.7%)
      approaches (p = 0.723). Cause of radiculopathy was the only significant factor
      affecting the efficacy of CIESI. Patients with disc herniation had significantly
      better results than patients with neural foraminal stenosis (82.9% vs. 56.0%) (p
      < 0.001). CONCLUSION: There is no significant difference in treatment efficacy
      between the midline and paramedian approaches in CIESI, for unilateral
      radiculopathy. The cause of the radiculopathy is significantly associated with
      the treatment efficacy; patients with disc herniation experience better pain
      relief than those with neural foraminal stenosis.

PMID- 25995691
TI  - Brown tumor of the patella caused by primary hyperparathyroidism: a case report.
AB  - It has been reported that the common sites of brown tumors are the jaw, pelvis,
      ribs, femurs and clavicles. We report our experience in a case of brown tumor of
      the patella caused by primary hyperparathyroidism. An initial radiograph and CT
      showed an osteolytic lesion and MR images showed a mixed solid and multiloculated
      cystic tumor in the right patella. One month after the parathyroidectomy, rapid
      bone formation was observed on both radiographs and CT images. 

PMID- 25995692
TI  - Effect of arterial deprivation on growing femoral epiphysis: quantitative
      magnetic resonance imaging using a piglet model.
AB  - OBJECTIVE: To investigate the usefulness of dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) and diffusion MRI for the evaluation of femoral head
      ischemia. MATERIALS AND METHODS: Unilateral femoral head ischemia was induced by
      selective embolization of the medial circumflex femoral artery in 10 piglets. All
      MRIs were performed immediately (1 hour) and after embolization (1, 2, and 4
      weeks). Apparent diffusion coefficients (ADCs) were calculated for the femoral
      head. The estimated pharmacokinetic parameters (Kep and Ve from two-compartment
      model) and semi-quantitative parameters including peak enhancement, time-to-peak
      (TTP), and contrast washout were evaluated. RESULTS: The epiphyseal ADC values of
      the ischemic hip decreased immediately (1 hour) after embolization. However, they
      increased rapidly at 1 week after embolization and remained elevated until 4
      weeks after embolization. Perfusion MRI of ischemic hips showed decreased
      epiphyseal perfusion with decreased Kep immediately after embolization. Signal
      intensity-time curves showed delayed TTP with limited contrast washout
      immediately post-embolization. At 1-2 weeks after embolization, spontaneous
      reperfusion was observed in ischemic epiphyses. The change of ADC (p = 0.043) and
      Kep (p = 0.043) were significantly different between immediate (1 hour) after
      embolization and 1 week post-embolization. CONCLUSION: Diffusion MRI and
      pharmacokinetic model obtained from the DCE-MRI are useful in depicting early
      changes of perfusion and tissue damage using the model of femoral head ischemia
      in skeletally immature piglets.

PMID- 25995693
TI  - Intravascular Placement of Metallic Coils as Lung Tumor Markers for CyberKnife
      Stereotactic Radiation Therapy.
AB  - OBJECTIVE: To present our experience with placing endovascular coils in pulmonary
      arteries used as a fiducial marker for CyberKnife therapy and to describe the
      technical details and complications of the procedure. MATERIALS AND METHODS:
      Between June 2005 and September 2013, 163 patients with primary or secondary lung
      malignancies, referred for fiducial placement for stereotactic radiosurgery, were
      retrospectively reviewed. Fourteen patients (9 men, 5 women; mean age, 70 years)
      with a history of pneumonectomy (n = 3), lobectomy (n = 3) or with severe
      cardiopulmonary co-morbidity (n = 8) underwent coil (fiducial marker) placement.
      Pushable or detachable platinum micro coils (n = 49) 2-3 mm in size were inserted
      through coaxial microcatheters into a small distal pulmonary artery in the
      vicinity of the tumor under biplane angiography/fluoroscopy guidance. RESULTS:
      Forty nine coils with a median number of 3 coils per tumor were placed with a
      mean tumor-coil distance of 2.7 cm. Forty three (87.7%) of 49 coils were
      successfully used as fiducial markers. Two coils could not be used due to a
      larger tumor-coil distance (> 50 mm). Four coils were in an acceptable position
      but their non-coiling shape precluded tumor tracking for CyberKnife treatment. No
      major complications needing further medication other than nominal therapy,
      hospitalization more than one night or permanent adverse sequale were observed.
      CONCLUSION: Endovascular placement of coil as a fiducial marker is safe and
      feasible during CyberKnife therapy, and might be an option for the patients in
      which percutaneous transthoracic fiducial placement might be risky.

PMID- 25995694
TI  - Quantitative Assessment of Global and Regional Air Trappings Using Non-Rigid
      Registration and Regional Specific Volume Change of Inspiratory/Expiratory CT
      Scans: Studies on Healthy Volunteers and Asthmatics.
AB  - OBJECTIVE: The purpose of this study was to compare air trapping in healthy
      volunteers with asthmatics using pulmonary function test and quantitative data,
      such as specific volume change from paired inspiratory CT and registered
      expiratory CT. MATERIALS AND METHODS: Sixteen healthy volunteers and 9 asthmatics
      underwent paired inspiratory/expiratory CT. DeltaSV, which represents the ratio
      of air fraction released after exhalation, was measured with paired inspiratory
      and anatomically registered expiratory CT scans. Air trapping indexes, DeltaSV0.4
      and DeltaSV0.5, were defined as volume fraction of lung below 0.4 and 0.5
      DeltaSV, respectively. To assess the gravity effect of air-trapping, DeltaSV
      values of anterior and posterior lung at three different levels were measured and
      DeltaSV ratio of anterior lung to posterior lung was calculated. Color-coded
      DeltaSV map of the whole lung was generated and visually assessed. Mean DeltaSV,
      DeltaSV0.4, and DeltaSV0.5 were compared between healthy volunteers and
      asthmatics. In asthmatics, correlation between air trapping indexes and clinical
      parameters were assessed. RESULTS: Mean DeltaSV, DeltaSV0.4, and DeltaSV0.5 in
      asthmatics were significantly higher than those in healthy volunteer group (all p
      < 0.05). DeltaSV values in posterior lung in asthmatics were significantly higher
      than those in healthy volunteer group (p = 0.049). In asthmatics, air trapping
      indexes, such as DeltaSV0.5 and DeltaSV0.4, showed negative strong correlation
      with FEF25-75, FEV1, and FEV1/FVC. DeltaSV map of asthmatics showed abnormal
      geographic pattern in 5 patients (55.6%) and disappearance of anterior-posterior
      gradient in 3 patients (33.3%). CONCLUSION: Quantitative assessment of DeltaSV
      (the ratio of air fraction released after exhalation) shows the difference in
      extent of air trapping between health volunteers and asthmatics.

PMID- 25995695
TI  - Effect of the high-pitch mode in dual-source computed tomography on the accuracy
      of three-dimensional volumetry of solid pulmonary nodules: a phantom study.
AB  - OBJECTIVE: To evaluate the influence of high-pitch mode (HPM) in dual-source
      computed tomography (DSCT) on the accuracy of three-dimensional (3D) volumetry
      for solid pulmonary nodules. MATERIALS AND METHODS: A lung phantom implanted with
      45 solid pulmonary nodules (n = 15 for each of 4-mm, 6-mm, and 8-mm in diameter)
      was scanned twice, first in conventional pitch mode (CPM) and then in HPM using
      DSCT. The relative percentage volume errors (RPEs) of 3D volumetry were compared
      between the HPM and CPM. In addition, the intermode volume variability (IVV) of
      3D volumetry was calculated. RESULTS: In the measurement of the 6-mm and 8-mm
      nodules, there was no significant difference in RPE (p > 0.05, respectively)
      between the CPM and HPM (IVVs of 1.2 +/- 0.9%, and 1.7 +/- 1.5%, respectively).
      In the measurement of the 4-mm nodules, the mean RPE in the HPM (35.1 +/- 7.4%)
      was significantly greater (p < 0.01) than that in the CPM (18.4 +/- 5.3%), with
      an IVV of 13.1 +/- 6.6%. However, the IVVs were in an acceptable range (< 25%),
      regardless of nodule size. CONCLUSION: The accuracy of 3D volumetry with HPM for
      solid pulmonary nodule is comparable to that with CPM. However, the use of HPM
      may adversely affect the accuracy of 3D volumetry for smaller (< 5 mm in
      diameter) nodule.

PMID- 25995696
TI  - Collateral Ventilation Quantification Using Xenon-Enhanced Dynamic Dual-Energy
      CT: Differences between Canine and Swine Models of Bronchial Occlusion.
AB  - OBJECTIVE: The aim of this study was to evaluate whether the difference in the
      degree of collateral ventilation between canine and swine models of bronchial
      obstruction could be detected by using xenon-enhanced dynamic dual-energy CT.
      MATERIALS AND METHODS: Eight mongrel dogs and six pigs underwent dynamic dual
      energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute
      wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period
      with segmental bronchus occluded. Ventilation parameters of magnitude (A value),
      maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were
      calculated from dynamic xenon maps using exponential function of Kety model.
      RESULTS: A larger difference in A value between parenchyma was observed in pigs
      than in dogs (absolute difference, -33.0 +/- 5.0 Hounsfield units [HU] vs. -2.8
      +/- 7.1 HU, p = 0.001; normalized percentage difference, -79.8 +/- 1.8% vs. -5.4
      +/- 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded
      parenchyma only decreased in pigs (all p < 0.05). K values of both periods were
      not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference
      was found in pigs in the wash-in period. TTP was delayed in the occluded
      parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). CONCLUSION: Xenon
      ventilation CT allows the quantification of collateral ventilation and detection
      of differences between canine and swine models of bronchial obstruction.

PMID- 25995697
TI  - Cryoablation of a small pulmonary nodule with pure ground-glass opacity: a case
      report.
AB  - Treatments for pure ground-glass nodules (GGNs) include limited resection;
      however, surgery is not always possible in patients with limited pulmonary
      functional reserve. In such patients, cryoablation may be a suitable alternative
      to treat a pure GGN. Here, we report our initial experience with cryoablation of
      a pure GGN that remained after repeated surgical resection in a patient with
      multiple GGNs. A 5-mm-sized pure GGN in the left lower lobe was cryoablated
      successfully without recurrence at the 6-month follow-up. 

PMID- 25995698
TI  - Extralobar pulmonary sequestration with hemorrhagic infarction in a child:
      preoperative imaging diagnosis and pathological correlation.
AB  - We describe a rare case of extralobar pulmonary sequestration with hemorrhagic
      infarction in a 10-year-old boy who presented with acute abdominal pain and
      fever. In our case, internal branching linear architecture, lack of enhancement
      in the peripheral portion of the lesion with internal hemorrhage, and vascular
      pedicle were well visualized on preoperative magnetic resonance imaging that led
      to successful preoperative diagnosis of extralobar pulmonary sequestration with
      hemorrhagic infarction probably due to torsion. 

PMID- 25995699
TI  - Right ventricular cardiomyopathy meeting the arrhythmogenic right ventricular
      dysplasia revised criteria? Don't forget sarcoidosis!
AB  - A 53-year-old woman was referred for ventricular fibrillation with resuscitation.
      A CT-angiography showed signs of a right ventricular enlargement without obvious
      cause. A cardiac MRI demonstrated a dilated and hypokinetic right ventricle with
      extensive late gadolinium enhancement. Arrhythmogenic right ventricular dysplasia
      (ARVD) was suspected according to the "revised ARVD task force criteria". An
      endomyocardial biopsy was inconclusive. The patient developed purulent
      pericarditis after epicardial ablation therapy and died of toxic shock syndrome.
      The post-mortem pathologic examination demonstrated sarcoidosis involving the
      heart, lungs, and thyroid gland. 

PMID- 25995700
TI  - Development of Coronary Vasospasm during Adenosine-Stress Myocardial Perfusion CT
      Imaging.
AB  - Adenosine is a short-acting coronary vasodilator, and it is widely used during
      pharmacological stress myocardial perfusion imaging. It has a well-established
      safety profile, and most of its side effects are known to be mild and transient.
      Until now, coronary vasospasm has been rarely reported as a side effect of
      adenosine during or after adenosine stress test. This study reports a case of
      coronary vasospasm which was documented on stress myocardial perfusion CT imaging
      during adenosine stress test. 

PMID- 25995701
TI  - Stenting for symptomatic vertebral artery stenosis associated with bilateral
      carotid rete mirabile: the long-term clinical and angiographic outcome.
AB  - Symptomatic vertebral artery (VA) stenosis associated with bilateral carotid rete
      mirabile (CRM) has not been reported. We report the long-term clinical and
      angiographic outcome after stenting for symptomatic VA stenosis in the patient
      with bilateral CRM. This report is the first case that symptomatic VA stenosis
      associated with bilateral CRM was treated with stenting. 

PMID- 25995702
TI  - Constructing cardiovascular fitness knowledge in physical education.
AB  - In physical education, it has become necessary for children to learn
      kinesiological knowledge for understanding the benefits of physical activity and
      developing a physically active lifestyle. This study was conducted to determine
      the extent to which cognitive assignments about healthful living and fitness
      contributed to knowledge growth on cardiorespiratory fitness and health. Fourth
      grade students (N = 616) from 15 randomly sampled urban elementary schools
      completed 34 cognitive assignments related to the cardiorespiratory physical
      activities they were engaged in across 10 lessons. Performance on the assignments
      were analyzed in relation to their knowledge gain measured using a standardized
      knowledge test. A multivariate discriminant analysis revealed that the cognitive
      assignments contributed to knowledge gain but the contribution varied assignment
      by assignment. A multiple regression analysis indicated that students' assignment
      performance by lesson contributed positively to their knowledge growth scores. A
      content analysis based on the constructivist learning framework showed that
      observing-reasoning assignments contributed the most to knowledge growth.
      Analytical and analytical-application assignments contributed less than the
      constructivist theories would predict.

PMID- 25995703
TI  - Hadronic bound states in SU(2) from Dyson-Schwinger equations.
AB  - By using the Dyson-Schwinger/Bethe-Salpeter formalism in Euclidean spacetime, we
      calculate the ground state spectrum of [Formula: see text] hadrons in an SU(2)
      gauge theory with two fundamental fermions. We show that the rainbow-ladder
      truncation, commonly employed in QCD studies, is unsuitable for a description of
      an SU(2) theory. This we remedy by truncating at the level of the quark-gluon
      vertex Dyson-Schwinger equation in a diagrammatic expansion. Results obtained
      within this novel approach show good agreement with lattice studies. These
      findings emphasize the need to use techniques more sophisticated than rainbow
      ladder when investigating generic strongly interacting gauge theories.

PMID- 25995704
TI  - HOLMES: The electron capture decay of [Formula: see text]Ho to measure the
      electron neutrino mass with sub-eV sensitivity.
AB  - The European Research Council has recently funded HOLMES, a new experiment to
      directly measure the neutrino mass. HOLMES will perform a calorimetric
      measurement of the energy released in the decay of [Formula: see text]Ho. The
      calorimetric measurement eliminates systematic uncertainties arising from the use
      of external beta sources, as in experiments with beta spectrometers. This
      measurement was proposed in 1982 by A. De Rujula and M. Lusignoli, but only
      recently the detector technological progress allowed to design a sensitive
      experiment. HOLMES will deploy a large array of low temperature microcalorimeters
      with implanted [Formula: see text]Ho nuclei. The resulting mass sensitivity will
      be as low as 0.4 eV. HOLMES will be an important step forward in the direct
      neutrino mass measurement with a calorimetric approach as an alternative to
      spectrometry. It will also establish the potential of this approach to extend the
      sensitivity down to 0.1 eV. We outline here the project with its technical
      challenges and perspectives.

PMID- 25995706
TI  - Rigorous theoretical constraint on constant negative EoS parameter [Formula: see
      text] and its effect for the late Universe.
AB  - In this paper, we consider the Universe at the late stage of its evolution and
      deep inside the cell of uniformity. At these scales, the Universe is filled with
      inhomogeneously distributed discrete structures (galaxies, groups and clusters of
      galaxies). Supposing that the Universe contains also the cosmological constant
      and a perfect fluid with a negative constant equation of state (EoS) parameter
      [Formula: see text] (e.g., quintessence, phantom or frustrated network of
      topological defects), we investigate scalar perturbations of the Friedmann
      Robertson-Walker metrics due to inhomogeneities. Our analysis shows that, to be
      compatible with the theory of scalar perturbations, this perfect fluid, first,
      should be clustered and, second, should have the EoS parameter [Formula: see
      text]. In particular, this value corresponds to the frustrated network of cosmic
      strings. Therefore, the frustrated network of domain walls with [Formula: see
      text] is ruled out. A perfect fluid with [Formula: see text] neither accelerates
      nor decelerates the Universe. We also obtain the equation for the nonrelativistic
      gravitational potential created by a system of inhomogeneities. Due to the
      perfect fluid with [Formula: see text], the physically reasonable solutions take
      place for flat, open and closed Universes. This perfect fluid is concentrated
      around the inhomogeneities and results in screening of the gravitational
      potential.

PMID- 25995707
TI  - Beyond standard model calculations with Sherpa.
AB  - We present a fully automated framework as part of the Sherpa event generator for
      the computation of tree-level cross sections in Beyond Standard Model scenarios,
      making use of model information given in the Universal FeynRules Output format.
      Elementary vertices are implemented into C++ code automatically and provided to
      the matrix-element generator Comix at runtime. Widths and branching ratios for
      unstable particles are computed from the same building blocks. The corresponding
      decays are simulated with spin correlations. Parton showers, QED radiation and
      hadronization are added by Sherpa, providing a full simulation of arbitrary BSM
      processes at the hadron level.

PMID- 25995705
TI  - Development of a general analysis and unfolding scheme and its application to
      measure the energy spectrum of atmospheric neutrinos with IceCube: IceCube
      Collaboration.
AB  - We present the development and application of a generic analysis scheme for the
      measurement of neutrino spectra with the IceCube detector. This scheme is based
      on regularized unfolding, preceded by an event selection which uses a Minimum
      Redundancy Maximum Relevance algorithm to select the relevant variables and a
      random forest for the classification of events. The analysis has been developed
      using IceCube data from the 59-string configuration of the detector. 27,771
      neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999
      % of the atmospheric muon background is achieved. The energy spectrum of the
      atmospheric neutrino flux is obtained using the TRUEE unfolding program. The
      unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100
      GeV to 1 PeV. Compared to the previous measurement using the detector in the 40
      string configuration, the analysis presented here, extends the upper end of the
      atmospheric neutrino spectrum by more than a factor of two, reaching an energy
      region that has not been previously accessed by spectral measurements.

PMID- 25995710
TI  - Teaching science content in nursing programs in Australia: a cross-sectional
      survey of academics.
AB  - BACKGROUND: Professional nursing practice is informed by biological, social and
      behavioural sciences. In undergraduate pre-registration nursing programs,
      biological sciences typically include anatomy, physiology, microbiology,
      chemistry, physics and pharmacology. The current gap in the literature results in
      a lack of information about the content and depth of biological sciences being
      taught in nursing curricula. The aim of this study was to establish what priority
      is given to the teaching of science topics in these programs in order to inform
      an understanding of the relative importance placed on this subject area in
      contemporary nursing education. METHOD: This study employed a cross-sectional
      survey method. This paper reports on the first phase of a larger project
      examining science content in nursing programs. An existing questionnaire was
      modified and delivered online for completion by academics who teach science to
      nurses in these programs. This paper reports on the relative priority given by
      respondents to the teaching of 177 topics contained in the questionnaire.
      RESULTS: Of the relatively small population of academics who teach science to
      nursing students, thirty (n = 30) completed the survey. Findings indicate strong
      support for the teaching of science in these programs, with particular priority
      given to the basic concepts of bioscience and gross system anatomy. Of concern,
      most science subject areas outside of these domains were ranked as being of
      moderate or low priority. CONCLUSION: While the small sample size limited the
      conclusions able to be drawn from this study, the findings supported previous
      studies that indicated inadequacies in the teaching of science content in nursing
      curricula. Nevertheless, these findings have raised questions about the current
      philosophy that underpins nursing education in Australia and whether existing
      practices are clearly focused on preparing students for the demands of
      contemporary nursing practice. Academics responsible for the design and
      implementation of nursing curricula are encouraged to review the content of
      current programs in light of the findings of this research.

PMID- 25995711
TI  - Supercapacitor electrode with a homogeneously Co3O4-coated multiwalled carbon
      nanotube for a high capacitance.
AB  - Cobalt oxide (Co3O4) was homogeneously coated on multiwalled carbon nanotube
      through a simple chemical deposition method and employed in supercapacitor
      electrodes. SEM image indicated the uniform distribution of Co3O4 nanoparticles
      on the surface of the multiwalled carbon nanotube. A maximum specific capacitance
      of 273 Fg(-1) was obtained at the charge-discharge current density of 0.5 Ag(-1).
      After 500 cycles of continuous charge-discharge process, about 88% of the initial
      capacity could be retained. 

PMID- 25995712
TI  - Investigation on the use of graphene oxide as novel surfactant to stabilize
      weakly charged graphene nanoplatelets.
AB  - This paper presents a unique synergistic behavior between a graphene oxide (GO)
      and graphene nanoplatelet (GnP) composite in an aqueous medium. The results
      showed that GO stabilized GnP colloid near its isoelectric point and prevented
      rapid agglomeration and sedimentation. It was considered that a rarely
      encountered charge-dependent electrostatic interaction between the highly charged
      GO and weakly charged GnP particles kept GnP suspended at its rapid coagulation
      and phase separation pH. Sedimentation and transmission electron microscope (TEM)
      micrograph images revealed the evidence of highly stable colloidal mixtures while
      zeta potential measurement provided semi-quantitative explanation on the
      mechanism of stabilization. GnP suspension was confirmed via UV-vis spectral data
      while contact angle measurement elucidated the close resemblance to an aqueous
      solution indicating the ability of GO to mediate the flocculation prone GnP
      colloids. About a tenfold increase in viscosity was recorded at a low shear rate
      in comparison to an individual GO solution due to a strong interaction manifested
      between participating colloids. An optimum level of mixing ratio between the two
      constituents was also obtained. These new findings related to an interaction
      between charge-based graphitic carbon materials would open new avenues for
      further exploration on the enhancement of both GO and GnP functionalities
      particularly in mechanical and electrical domains. 

PMID- 25995713
TI  - Dielectric behavior of ceramic-graphene composites around the percolation
      threshold.
AB  - Al2O3/graphene and BaTiO3/graphene composites with different concentrations of
      the conductive second phase, both below and above the percolation threshold, were
      prepared by the traditional ceramic processing route followed by spark plasma
      sintering. It is shown that the addition of graphene pins the grain growth of the
      ceramic matrix grains, leading to a change of the microstructure at low filler
      concentrations. As a consequence, the composites exhibit two percolation
      thresholds and their dielectric properties are not only determined by the
      dielectric properties of the constituents and their relative fractions but also
      the microstructure of the composite must be considered. Additionally, a giant
      increase of the dielectric constant has been found around the percolation
      thresholds in barium titanate-graphene composites. In particular, values of the
      dielectric constant up to 45,000 and 15,000 were found at 1 kHz in composites
      containing 0.4 and 0.6 wt. % graphene, respectively. 

PMID- 25995714
TI  - Anti-EGFR-Conjugated Hollow Gold Nanospheres Enhance Radiocytotoxic Targeting of
      Cervical Cancer at Megavoltage Radiation Energies.
AB  - The study aimed to confirm that anti-epidermal growth factor receptor (EGFR)
      monoclonal antibody-conjugated hollow gold nanospheres (anti-EGFR/HGNs) can be
      selectively uptaken by cervical cancer cells and induce its apoptosis when
      combined with radiotherapy, as a result enhancing radiosensitivity of cervical
      cancer cells. HGNs with a mean diameter of 54.6 +/- 7.11 nm and wall thickness of
      5.01 +/- 2.23 nm were viewed by transmission electron microscopy (TEM). Cell
      uptake was assayed by inductively coupled plasma atomic emission spectroscopy
      (ICP-AES). The cytotoxicity on HeLa cells, which were used in our experiment, was
      assessed by CCK-8 assay. Cell cycle and apoptosis were examined by an Annexin V
      FITC/propidium iodide (PI) kit with flow cytometry (FCM). The expression of
      several critical apoptosis-related proteins, including Bcl-2, Bax, Bad, and
      active caspase 3, was tested by western blot analysis. Cells treated by anti
      EGFR/HGNs showed an obvious increase in nanoparticle uptake compared to naked
      HGNs. Anti-EGFR/HGNs combined with radiation resulted in a significant growth
      inhibition, compared with radiation combined with naked HGNs. Anti-EGFR/HGNs
      remarkably increased the ratio of HeLa cells in the G2/M phase and induced more
      apoptosis by an obvious deregulation of Bcl-2 and upregulation of Bax, Bad, and
      caspase 3 when combined with radiation. Therefore, anti-EGFR/HGNs can increase
      the targeted uptake of HGNs by HeLa cells and enhance radiocytotoxic targeting of
      cervical cancer at megavoltage radiation energies. 

PMID- 25995715
TI  - Merging worlds of nanomaterials and biological environment: factors governing
      protein corona formation on nanoparticles and its biological consequences.
AB  - Protein corona has became a prevalent subject in the field of nanomedicine owing
      to its diverse role in determining the efficiency, efficacy, and the ultimate
      biological fate of the nanomaterials used as a tool to treat and diagnose various
      diseases. For instance, protein corona formation on the surface of nanoparticles
      can modify its physicochemical properties and interfere with its intended
      functionalities in the biological microenvironments. As such, much emphasis
      should be placed in understanding these complex phenomena that occur at the bio
      nano interface. The main aim of this review is to present different factors that
      are influencing protein-nanoparticle interaction such as physicochemical
      properties of nanoparticle (i.e., size and size distribution, shape, composition,
      surface chemistry, and coatings) and the effect of biological microenvironments.
      Apart from that, the effect of ignored factors at the bio-nano interface such as
      temperature, plasma concentration, plasma gradient effect, administration route,
      and cell observer were also addressed. 

PMID- 25995716
TI  - Predictors of acute diarrhoea among hospitalized children in Gaza Governorates: a
      case-control study.
AB  - This study aims to determine the predictors of acute diarrhoea among hospitalized
      children in the Gaza Governorates. The case-control design included 140 children
      (70 cases and 70 controls) in a stratified cluster sample from Naser Medical
      Complex and Alnasser Pediatric Hospital. An interview questionnaire was used, and
      face and content validations were performed. Multiple logistic regression was
      used for the multivariate analysis of risk factors of diarrhoea in children aged
      less than five years. Results showed a significant association between diarrhoea
      and family income, residence, complementary feeding, and age of weaning (p<0.05).
      Children living in villages had lower odds of having diarrhoea by 53.2% than
      children living in cities. Children of families with incomes between US$ 485 and
      620 had lower odds of having diarrhoea by 80.8% than children of families with
      incomes less than US$ 485. Moreover, children who did not receive complementary
      feeding had lower odds of having diarrhoea by 59.0%. We found that, for one month
      increase in weaning age, the odds of diarrhoea decreased by 1.06 times (adjusted
      OR=1.05, 95% CI 1.0180-1.100). The study concludes that urban residence, lower
      family income, complementary feeding, and lower age of weaning are risk factors
      of diarrhoea among children aged less than five years in the Gaza Strip. The
      results of the study suggest that children of low-income families and those who
      were not naturally breastfed may warrant more attention for prevention and/or
      treatment of diarrhoea. 

PMID- 25995717
TI  - Promotion of zinc tablets with ORS through child health weeks improves caregiver
      knowledge, attitudes, and practice on treatment of diarrhoea in Nigeria.
AB  - We examined whether the Maternal, Newborn and Child Health Weeks (MNCHW) in
      Nigeria would present an opportunity to raise awareness of and demand for the use
      of zinc and ORS in the treatment for diarrhoea, guided by a conceptual framework
      designed to assess three theoretical underpinnings (characteristics and
      performance standard of the health workers, potential reach, and intensity of the
      intervention), along the impact pathway. Zinc and ORS with education for their
      appropriate use during the next diarrhoeal episode were delivered as part of the
      November 2010 and May 2011 MNCHW. On the day of but before participating in MNCHW
      activities, semi-structured interviews were used for collecting information on
      knowledge, attitudes, and practice (KAP) relating to diarrhoea from 602
      caregivers with children aged less than five years. Forty-eight health workers
      were also interviewed. Nearly all health workers (98%) correctly mentioned the
      dosage of zinc while only 58% correctly stated the preparation of ORS. The
      proportion of caregivers with knowledge on the treatment for diarrhoea increased
      from 46.4% in November 2010 pre-MNCHW to 71.3% in May 2011 pre-MNCHW interviews
      (p<0.001). More caregivers correctly mentioned the dosage of zinc (80.9%) and
      stated the preparation of ORS (88.8%) in the November 2010 exit interview
      immediately after the MNCHW encounter compared to the levels a few months later
      in the home follow-up visit (53.1% and 37.4% respectively). After attending both
      rounds of November 2010 and May 2011 MNCHW, caregivers' knowledge on the
      treatment of diarrhoea increased seven times compared to the caregivers who
      attended the May 2011 MNCHW only (OR=7.0, p<0.001). Additionally, caregivers were
      40% less likely to seek advice outside the home in the treatment for diarrhoea if
      they had attended both the MNCHWs than if they had attended the May 2011 MNCHW
      only (OR=0.6, p<0.029). We conclude that providing opportunities for caregivers
      to receive a sample of zinc and ORS and to learn about its use in the treatment
      for diarrhoea, from trained health workers during MNCHW, has the potential to
      increase KAP relating to the use of zinc and ORS in the treatment for diarrhoea
      and for future diarrhoeal episodes. 

PMID- 25995718
TI  - Knowledge, perception, and management skills of mothers with under-five children
      about diarrhoeal disease in indigenous and resettlement communities in Assosa
      District, Western Ethiopia.
AB  - As primary caregiver to under-five children in Ethiopia, mothers' knowledge,
      perception, and management skills are important to minimize the effects of
      morbidity and mortality associated with diarrhoeal diseases. A community-based
      comparative cross-sectional study was conducted in Abramo and Megele 37 kebeles
      (the last administration division) in Assosa district of western Ethiopia in July
      2010. Quantitative data were obtained by a structured questionnaire from 232
      randomly-selected mothers having children aged less than five years regarding
      their knowledge, perception, and management. Qualitative data were also collected
      by arranging four focus group discussions involving mothers from the two
      communities. The prevalence of diarrhoeal diseases among under-five children was
      33.2%, and the knowledge of mothers about the causes, transmission, and
      prevention of diarrhoea in the study area was 37.5%. The prevalence of diarrhoeal
      disease was higher in the settlement area whereas mothers' knowledge was better
      in the indigenous community; 62.9% of mothers were categorized as having good
      attitude on causes, transmission, and prevention of diarrhoeal disease. Community
      water source, water storage container, and knowledge of mothers remained a strong
      predictor of diarrhoeal morbidity after conducting logistic regression analysis
      (OR=8.4, CI 3.59-31.85; OR=2.2, CI 1.02-4.89; and OR=3.62, CI 1.23-4.71
      respectively). Diarrhoeal morbidity was high in the study areas. On the contrary,
      knowledge and attitude of mothers, recognizing the danger sign of dehydration due
      to diarrhoea, and the prevention and management of childhood diarrhoeal diseases
      were not adequate. Information, education and communication strategy may help
      increase the knowledge and create positive attitude among mothers regarding the
      cause, prevention, and management of diarrhoea. 

PMID- 25995719
TI  - Cholera outbreak linked with lack of safe water supply following a tropical
      cyclone in Pondicherry, India, 2012.
AB  - In the aftermath of a severe cyclonic storm on 7 January 2012, a cluster of acute
      diarrhoea cases was reported from two localities in Pondicherry, Southern India.
      We investigated the outbreak to identify causes and recommend control measures.
      We defined a case as occurrence of diarrhoea of more than three loose stools per
      day with or without vomiting in a resident of affected areas during 6-18 January
      2012. We used active (door-to-door survey) and stimulated passive (healthy
      facility-based) surveillance to identify cases. We described the outbreak by
      time, place, and person. We compared the case-patients with up to three controls
      without any apparent signs and symptoms of diarrhoea and matched for age, gender,
      and neighbourhood. We calculated matched odds ratio (MOR), 95% confidence
      intervals (CI), and population attributable fractions (PAF). We collected rectal
      swabs and water samples for laboratory diagnosis and tested water samples for
      microbiological quality. We identified 921 cases and one death among 8,367
      residents (attack rate: 11%, case-fatality: 0.1%). The attack rate was the
      highest among persons of 50 years and above (14%) and females (12%). The outbreak
      started on 6 January and peaked on the 9th and lasted till 14 January. Cases were
      clustered around two major leakages in water supply system. Nine of the 16 stool
      samples yielded V. cholerae O1 Ogawa. We identified that consumption of water
      from the public distribution system (MOR=37, 95% CI 4.9-285, PAF: 97%), drinking
      unboiled water (MOR=35, 95% CI 4.5-269, PAF: 97%), and a common latrine used by
      two or more households (MOR=2.7, 95% CI 1.3-5.6) were independently associated
      with cholera. Epidemiological evidence suggested that this outbreak was due to
      ingestion of water contaminated by drainage following rains during cyclone. We
      recommended repair of the water supply lines, cleaning-up of the drains,
      handwashing, and drinking of boiled water. 

PMID- 25995720
TI  - Dietary patterns and risk of gallbladder disease: a hospital-based case-control
      study in adult women.
AB  - Gallbladder disease is one of the most prevalent gastrointestinal disorders that
      may result from a complex interaction of genetic and environmental factors. This
      study examined the association of dietary patterns with gallstone disease among
      Iranian women. This case-control study was conducted in general teaching
      hospitals in Tehran, Iran. Participants were 101 female cases and 204 female
      controls aged 40-65 years who were admitted for problems other than GBD. Dietary
      patterns were identified using principal components analysis based on food
      frequency questionnaire. Compared to the control group, cases were less educated,
      less physically active, and consumed more total energy (p<0.02). Having >= 3
      livebirths increased the risk of gallstone by more than 5 times, followed by
      having rapid weight loss, being single, having familial history of gallstone, and
      consuming high total energy. Two distinct dietary patterns were identified in
      women (healthy and unhealthy). After adjustment for several confounding
      variables, healthy dietary pattern was associated with a decreased risk of
      gallstone disease (OR=0.14, 95% CI 0.048-0.4) while unhealthy dietary pattern was
      associated with an increased risk (OR=3.77, 95% CI 1.52-9.36). These findings
      confirm that dietary pattern approach provides potentially useful and relevant
      information on the relationship between diet and disease. Identifying risk
      factors will provide an opportunity for prevention of gallbladder disease in
      developing countries facing an increased risk of obesity.

PMID- 25995721
TI  - Validity and reproducibility of a revised semi-quantitative food frequency
      questionnaire (SQFFQ) for women of age-group 12-44 years in Chengdu.
AB  - To find a credible nutritional screening tool for evaluating relationship between
      nutritional status and diseases in Chengdu female residents, the reliability and
      validity of a revised semi-quantitative food frequency questionnaire (SQFFQ) were
      tested. The validity was assessed by comparing the SQFFQ with the 'standard'
      method of 3 days' dietary recall, and the reliability was assessed by comparing
      the first SQFFQ with the second SQFFQ at 4 weeks interval. Correlation analysis
      showed that, for reliability, the average correlation coefficient (CC) of 22
      kinds of nutrients was 0.66 and reduced to 0.60 after adjusting for energy; the
      average of intra-class correlation coefficients (ICC) was 0.65. For validity, the
      average CC was 0.35 and remained stable after adjusting for CC of energy or
      nutrients. Validity of 17 nutrients in SQFFQ survey had correlation with result
      of 3 days' dietary recall. The results showed that the revised SQFFQ can be used
      for investigating the role of nutrients in development of disease in Chengdu
      female residents. 

PMID- 25995722
TI  - Sensory evaluation of locally-grown fruit purees and inulin fibre on probiotic
      yogurt in Mwanza, Tanzania and the Microbial Analysis of Probiotic Yogurt
      Fortified with Moringa oleifera.
AB  - The purpose of this study was to establish new food products that increase the
      nutritional value and health benefits of the probiotic yogurt currently used in
      the Western Heads East (WHE) Project in Mwanza, Tanzania. The probiotic yogurt
      has established health benefits, and product development through fortification
      must not adversely affect the acceptability of yogurt or the viability of the
      probiotics. Both sensory testing and microbial analysis testing were conducted.
      The products tested were yogurt fortified with locally-grown fruit purees with
      inulin and Moringa oleifera. The results of the sensory evaluation showed that
      all yogurts were not rated significantly different from the control, except for
      appearance. The avocado puree without inulin rated significantly lower in all
      categories. The microbial analysis showed that Moringa oleifera did not
      negatively affect the growth of Lactobacillus rhamnosus GR-1 in MRS, milk or
      yogurt, although a significant decrease was found after 5 weeks of storage at 4
      (o)C. 

PMID- 25995723
TI  - Predictors of dietary supplement usage among medical interns of Tehran university
      of medical sciences.
AB  - This study aimed to determine the prevalence of dietary supplement-use and its
      relationship with demographics and lifestyle of medical interns. The study sample
      comprised 356 interns aged 23 to 25 years. Participants completed a questionnaire
      on dietary supplement-use during the month preceding the study, information on
      demographic characteristics and lifestyle was also obtained. Univariable and
      multivariable logistic regression were employed to assess the correlates of
      dietary supplement-use. The prevalence of dietary supplement-use was about 33%
      (males 20.4% and females 43.2%, p<0.001). The most commonly-used dietary
      supplement was multivitamin/multivitamin-mineral (90.6% in males and 52.3% in
      females). Approximately 30% of supplements were used regularly (>= 5 days/week)
      by all subjects. The most-frequently reported reasons for supplement-use in males
      were: enhancing daily energy/stamina (51.1%), poor food intake (13.3%) and, in
      females, were: improving health and nutritional status (39.3%) and reducing hair
      loss (23.4%). The decision to use dietary supplement was mostly driven by the
      interns themselves (56% in males, 61% in females). In the univariable analysis,
      men who exercised once or twice a week were less likely to use supplements
      compared to those who reported doing exercise more than twice weekly (OR=0.35,
      95% CI 0.12-0.98). Females who reported their health status to be 'excellent'
      were more likely to use supplements compared to those who described their health
      status as 'moderate/poor/very poor' (OR=2.53, 95% CI 1.15-5.56) as were women who
      mentioned their breakfast consumption status as 'always' (OR=2.69, 95% CI 1.47
      4.92). In the multivariable analysis, only breakfast consumption was
      significantly related with dietary supplement-use in females (OR=2.20, 95% CI
      1.11-4.38). In conclusion, dietary supplement-use among medical interns,
      especially among females, was relatively very common. Dietary supplement-use was
      related to a healthier lifestyle.

PMID- 25995724
TI  - Healthy eating habits among the population of Serbia: gender and age differences.
AB  - The purpose of the study is to examine healthy eating habits of the population of
      Serbia through three dimensions: knowledge, problems, and feelings as well as to
      determine whether there are any differences between genders and among different
      age-groups. The research instrument was an Eating Habits Questionnaire (EHQ)
      which consisted of 35 items. There were 382 respondents involved in the study.
      The reliability and factor structure of the questionnaire were verified by using
      factor analysis. The results of MANOVA showed that there is a significant
      difference in the habits concerning healthy eating between men and women [F
      (3,378)=4.26, p=0.006; Wilks' Lambda=0.97]. When the results for the dependent
      variables (knowledge, problems, and feelings) were considered separately, it was
      determined that there is no significant difference between men and women, which
      confirms the results of the t-test. The effect of age on the three dimensions of
      healthy eating habits was examined within three age-groups, by using ANOVA. The
      results showed that knowledge about healthy eating increases with age [F
      (2,379)=6.14, p=0.002] as well as positive feelings which occur as a result of
      healthy eating [F (2,379)=3.66, p=0.027]. Unlike ANOVA, MANOVA showed difference
      among the age-groups only when it came to the 'knowledge' variable. This study is
      important as it shows the current state of awareness on healthy eating habits in
      the researched populace and may be the basis for further research in this field
      in Serbia. 

PMID- 25995726
TI  - Dual burden of underweight and overweight among women in Bangladesh: patterns,
      prevalence, and sociodemographic correlates.
AB  - The discourse of dual burden caused through underweight and overweight is well
      documented globally but this issue and its connection with women's health in
      Bangladesh is yet to be explored widely. To enrich the current debate, this
      study, in the context of Bangladesh, examines the patterns, prevalence, and
      socioeconomic factors influencing the ever-married women of being underweight and
      overweight over normal weight. Data used in this study have been extracted from
      the most recent 2011 Bangladesh Demographic and Health Survey. To achieve results
      connected with the research objectives, both bivariate and multivariate
      statistical analyses have been employed. In bivariate analysis, we used seven
      categories of BMI cutoff points for Asian countries as prescribed by World Health
      Organization (WHO). Multinomial logistic regression model was constructed to
      investigate the net effect of socioeconomic factors on underweight, pre
      overweight, and overweight over normal weight. The results confirm the co
      existence of underweight and overweight among women as we found the prevalence of
      underweight, normal weight, pre-overweight, overweight, and obesity to be 24.1%,
      46.7%, 12.8%, 13.5%, and 2.9% respectively. Compared to the richest, the women
      from the poorest households were significantly (p<0.001) most likely to be
      underweight (OR=2.75, 95% CI 2.27-3.35) and least likely to be overweight
      (OR=0.15, 95% CI 0.12-0.19) over normal weight. The urban women, compared to
      their rural counterparts, were significantly (p<0.001) less likely to be
      underweight (OR=0.80, 95% CI 0.71-0.91) and more likely to be overweight
      (OR=1.33, 95% CI 1.18-1.51) than normal weight. The other socioeconomic grades
      that were most marked to be underweight and overweight are age, women's
      education, marital status, age at first childbirth, parity, number of children
      aged <= 5 years at the household, and food security. The findings confirm the
      dual burden of both under- and overweight. Systematic and regular monitoring and
      surveillance of the social trajectory of nutritional status of women and men in
      Bangladesh is crucial to develop opposite strategy that addresses the persistent
      and chronic problem of underweight and the emerging problem of overweight. The
      dual existence of both types of malnutrition among women in Bangladesh must be
      taken into consideration so that public health interventions may be adopted
      through appropriate policy.

PMID- 25995725
TI  - Protective effect of breastfeeding against overweight can be detected as early as
      the second year of life: a study of children from one of the most socially
      deprived areas of Brazil.
AB  - Millions of children live in Brazil's semi-arid region, one of the most socially
      deprived areas of the country, where undernutrition co-exists with obesity as a
      consequence of the nutrition transition. There is evidence that childhood obesity
      predisposes adult obesity and, thus, that obesity should be prevented as early as
      possible. Some studies have shown that breastfeeding is a protective factor
      against overweight and obesity while other studies have not found this
      association. There have been few studies on this association in developing
      countries and of children below two years of age. The present study aimed to
      investigate whether children exposed to exclusive breastfeeding for >= 6 months
      showed a lower prevalence of overweight in the second year of life, based on a
      probability sample of 2,209 children (aged 12 to 24 months). The dependent
      variable was overweight, defined as weight-for-length z-scores of >2, based on
      the WHO 2006 standard while the independent variable was exclusive breastfeeding
      (>= 6 months). The prevalence ratio (PR) and its 95% CI were estimated using
      Poisson regression with robust adjustment of variance. After adjusting for
      potential confounding factors (socioeconomic, demographic and health-related
      variables), children on exclusive breastfeeding for >= 6 months showed a lower
      prevalence of overweight (5.7% vs 9.1%, PR 0.62, 95% CI 0.45-0.89). It was found
      that exclusive breastfeeding for six months or more is a protective factor
      against overweight in children in the second year of life living in the Brazilian
      semi-arid region.

PMID- 25995727
TI  - Barriers to infant and child-feeding practices: a qualitative study of primary
      caregivers in Rural Uganda.
AB  - The purpose of this study was to explore the barriers to the use of appropriate
      infant and young child-feeding practices by primary caregivers living in a rural
      Ugandan district. A community-based qualitative design and focus group
      discussions were used for collecting data from primary caregivers of children
      aged 0 to 24 month(s). On an average, each of the four focus group discussions
      had 11 participants. The focus group discussions were conducted using a
      structured interview guide and were tape-recorded. The recorded data were later
      transcribed and analyzed using qualitative thematic analysis techniques. All the
      participants were females, and the majority had low levels of education and at
      least one child in the age-group of 0-24 month(s) in their household. The
      findings show that the main barriers to the use of appropriate infant and young
      child-feeding practices fall under four themes: caregiver's knowledge about
      breastfeeding, caregiver's knowledge about complimentary feeding, influence of
      culture custodians on the caregivers, and patterns and burden of other
      responsibilities the caregivers have in the household. The four categories of
      barriers imply that there are various missed opportunities to implement hospital
      and community-based interventions to improve infant and young child-feeding
      practices, which is one way of preventing malnutrition. Therefore, in rural areas
      of Uganda, the major factors responsible for the high prevalence of malnutrition
      among infants and children are still those related to knowledge, culture, and
      social status of the primary caregivers. 

PMID- 25995728
TI  - Infant formula crisis in china: a cohort study in sichuan province.
AB  - China has become the largest market of infant formula in the world. The
      consumption of infant formula is widespread across the country. This study
      investigated the opinions of Chinese mothers on infant formula. A prospective
      cohort study (n=695) was undertaken in 2011 in Sichuan province of China two
      years after the melamine scandal. Infant-feeding practices and mothers' opinions
      on infant formula-use were documented in detail. A total of 674 mothers (97%) had
      initiated breastfeeding by discharge. Of the 21 mothers who did not commence
      breastfeeding, 13 made a decision to exclusively feed their babies with infant
      formula because of hepatitis B virus infection. Nearly 70% of newborns received
      infant formula as their first feed, and the prevalence increased to 88% within
      one month. Having insufficient breastmilk was perceived by the majority (77%) of
      mothers as the reason behind infant formula feeding. About half (46%) of the
      mothers agreed with or were ambivalent that infant formula feeding does not
      reduce their breastmilk production. More than one-third (38%) of women thought
      that formulafed infants sleep longer at night than those who are breastfed. In
      addition, this perception was positively associated with the use of formula
      within one month postpartum (p=0.003). In conclusion, mothers' opinions appear to
      influence the use of infant formula in China. There is a need for further
      education on breastfeeding and infant-feeding options to maintain and improve
      breastfeeding outcomes in China. 

PMID- 25995729
TI  - Neglected value of small population-based surveys: a comparison with demographic
      and health survey data.
AB  - We believe that global health practice and evaluation operate with misleading
      assumptions about lack of reliability of small population-based health surveys
      (district level and below), leading managers and decision-makers to under-use
      this valuable information and programmatic tool and to rely on health information
      from large national surveys when neither timing nor available data meet their
      needs. This paper uses a unique opportunity for comparison between a knowledge,
      practice, and coverage (KPC) household survey and Rwanda Demographic and Health
      Survey (RDHS) carried out in overlapping timeframes to disprove these enduring
      suspicions. Our analysis shows that the KPC provides coverage estimates
      consistent with the RDHS estimates for the same geographic areas. We discuss
      cases of divergence between estimates. Application of the Lives Saved Tool to the
      KPC results also yields child mortality estimates comparable with DHS-measured
      mortality. We draw three main lessons from the study and conclude with
      recommendations for challenging unfounded assumptions against the value of small
      household coverage surveys, which can be a key resource in the arsenal of local
      health programmers. 

PMID- 25995730
TI  - Assessment of 'accredited social health activists'-a national community health
      volunteer scheme in Karnataka State, India.
AB  - About 700,000 Accredited Social Health Activists (ASHA) have been deployed as
      community health volunteers throughout India over the last few years. The
      objective of our study was to assess adherence to selection criteria in the
      recruitment of ASHA workers and to assess their performance against their job
      descriptions in Karnataka state, India. A cross-sectional survey, using a
      combination of quantitative and qualitative methods, was undertaken in 2012.
      Three districts, 12 taluks (subdistricts), and 300 villages were selected through
      a sequential sampling scheme. For the quantitative survey, 300 ASHAs and 1,800
      mothers were interviewed using sets of structured questionnaire. For the
      qualitative study, programme officers were interviewed via in-depth interviews
      and focus group discussions. Mean +/- SD age of ASHAs was 30.3 +/- 5.0 years, and
      about 90% (261/294) were currently married, with eight years of schooling. ASHAs
      were predominantly (>80%) involved in certain tasks: home-visits, antenatal
      counselling, delivery escort services, breastfeeding advice, and immunization
      advice. Performance was moderate (40-60%) for: drug provision for tuberculosis,
      caring of children with diarrhoea or pneumonia, and organizing village meetings
      for health action. Performance was low (<25%) for advice on: contraceptive-use,
      obstetric danger sign assessment, and neonatal care. This was self-reported by
      ASHAs and corroborated by mothers. In conclusion, ASHA workers were largely
      recruited as per preset selection criteria with regard to age, education, family
      status, income, and residence. The ASHA workers were found to be functional in
      some areas with scope for improvement in others. The role of an ASHA worker was
      perceived to be more of a link-worker/facilitator rather than a community health
      worker or a social activist.

PMID- 25995731
TI  - Association of alcohol consumption with specific biomarkers: a cross-sectional
      study in South Africa.
AB  - Alcohol consumption plays an important role in the health transition associated
      with urbanization in developing countries. Thus, reliable tools for assessing
      alcohol intake levels are necessary. We compared two biological markers of
      alcohol consumption and self-reported alcohol intakes in participants from urban
      and rural South African communities. This cross-sectional epidemiological survey
      was part of the North West Province, South African leg of the 12-year
      International Prospective Urban and Rural Epidemiology (PURE) study which
      investigates the health transition in urban and rural subjects. A total of 2,010
      apparently healthy African volunteers (35 years and older) were recruited from a
      sample of 6,000 randomly-selected households. Alcohol consumption was assessed
      through self-reports (24-hour recalls and quantitative food frequency
      questionnaire) and by two biological markers: percentage carbohydrate-deficient
      transferrin (%CDT) and gamma-glutamyl transferase (GGT). Of the 716 men and 1,192
      women volunteers, 64% and 33% respectively reported regular alcohol consumption.
      Reported mean habitual intakes of drinker men and women were 29.9 (+/- 30.0) and
      23.3 (+/- 29.1) g of pure alcohol per day. Reported habitual intake of the whole
      group correlated positively and significantly with both %CDT (R=0.32; p <= 0.01)
      and GGT (R=0.43; p <= 0.01). The correlation between the two biomarkers was low
      (0.211; p <= 0.01). GGT and %CDT values should be interpreted with care in
      Africans as self-reported non-drinker men and women had elevated levels of GGT
      (19% and 26%) and %CDT (48% and 38%). A need exists for a more specific
      biological marker for alcohol consumption in black Africans.

PMID- 25995732
TI  - Association of insulin resistance with lipid profile, metabolic syndrome, and
      hormonal aberrations in overweight or obese women with polycystic ovary syndrome.
AB  - This cross-sectional study was aimed to better clarify the associations of
      insulin resistance (IR) with endocrinometabolic parameters in polycystic ovary
      syndrome (PCOS). Anthropometric measurements, endocrine and metabolic profiles,
      and the presence of IR and metabolic syndrome (MetS) were assessed in 63
      overweight or obese PCOS patients subdivided into insulin-resistant (IR) and
      insulin-sensitive (IS) groups. Fasting insulin concentration and HOMA-IR were
      higher (p<0.001), and quantitative insulin check index (QUICKI), glucose-to
      insulin ratio (p<0.001), and high-density lipoprotein cholesterol (HDL-C)
      (p=0.012) were lower in IR group. MetS (p=0.034) and obesity (p=0.038) were more
      prevalent in IR group. For all PCOS patients, significant correlations of total
      cholesterol (TC) with dehydroepiandrosterone sulphate (DHEAS) (r=-0.27, p=0.031),
      HDL-C with QUICKI (r=0.26, p=0.036) were found. Partial correlations also showed
      significant associations between TG and BS2h (r=0.30, p=0.026) as well as TC and
      LH/FSH ratio (r=0.30, p=0.032). When the patients were divided into IR and IS
      groups, significant correlations of low-density lipoprotein cholesterol (LDL-C)
      with luteinizing hormone (LH) (r=0.50, p=0.017) as well as TC (r=0.42, p=0.043)
      and LDL-C (r=0.50, p=0.016) with LH/FSH ratio were observed in IR group. However,
      partial correlation suggested significant associations of HDL-C with testosterone
      (r=-0.35, p=0.049) as well as serum LDL-C (r=0.38, p=0.033), HDL-C (r=-0.32,
      p=0.047), and TC (r=0.34, p=0.056) with progesterone level only in the IS group.
      The findings of this study indicated that lipid abnormalities may occur in PCOS,
      irrespective of IR. 

PMID- 25995733
TI  - Relationship between sociodemographics, dietary intake, and physical activity
      with gestational weight gain among pregnant women in Rafsanjan City, Iran.
AB  - Gestational weight gain (GWG) is a determinant of health and nutrition of mothers
      and offspring. However, many factors associated with GWG are not completely
      understood. The present study assessed the relationship between
      sociodemographics, dietary intake, and physical activity with GWG in 308 Iranian
      pregnant women attending government healthcare centres in Rafsanjan city, Iran.
      Women gained an average of 12.87+/-3.57 kg during pregnancy while 54% did not
      gain weight within the Institute of Medicine (IOM)-recommended range. Univariate
      logistic models showed that gestaional weight gain was related to age, pre
      pregnancy body mass index (BMI), energy intake, and sitting time. Cumulative
      logit model showed positive relationship between age (p=0.0137) and pre-pregnancy
      BMI (p<0.0001) with GWG. All pregnant women should be counselled on achieving the
      reccomended GWG to prevent adverse maternal and prenatal outcomes. Pre-pregnancy
      and gestational nutritional status and physical activity should be emphasized in
      antenatal care. 

PMID- 25995734
TI  - Primary health centres: preferred option for birthing care in tamilnadu, India,
      from users' perspectives.
AB  - Tamilnadu state of India witnessed an increasing trend of institutional
      deliveries since the beginning of 1990s, with decline of domiciliary deliveries
      to nearly zero now. Among the institutional deliveries, a shift has been observed
      since 2006 wherein primary health centres (PHC) have shown a four-fold increase
      in the number of deliveries while other public and private health facilities
      showed a decline, despite equal access by people to all categories of health
      facilities. A qualitative study was designed to explore the determinants that led
      to increased preference of PHCs for birthing care. In-depth interviews and FGDs
      were conducted with recently-delivering women and their spouses. User-friendly
      ambience, courteous attitude and behaviour of staff, good infrastructure,
      availability of qualified staff, and relative absence of informal payments have
      contributed to increased preference for birthing care in PHCs. Barriers to
      seeking care from secondary and tertiary-level public hospitals and private
      hospitals have also made women prefer PHCs. 

PMID- 25995735
TI  - Unmet need for family planning: implication for under-five mortality in Nigeria.
AB  - There are gaps in evidence on whether unmet need for family planning has any
      implication for under-five mortality in Nigeria. This study utilized 2008 Nigeria
      Demographic and Health Survey data to examine the effect of unmet need on under
      five mortality. Cox regression analysis was performed on 28,647 children born by
      a nationally-representative sample of 18,028 women within the five years
      preceding the survey. Findings indicated elevated risks of under-five death for
      children whose mothers had unmet need for spacing [Hazard ratio (HR): 1.60,
      confidence interval (CI) 1.37-1.86, p<0.001] and children whose mothers had unmet
      need for limiting (HR: 1.78, CI 1.48-2.15, p<0.001) compared to children whose
      mothers had met need. These findings were consistent after adjusting for the
      effects of factors that could confound the association. Findings of this study
      underscore the need to address the present level of unmet need for family
      planning in Nigeria, if the country would achieve meaningful reduction in under
      five mortality. 

PMID- 25995736
TI  - A model immunization programme to control Japanese encephalitis in Viet Nam.
AB  - In Viet Nam, an inactivated, mouse brain-derived vaccine for Japanese
      encephalitis (JE) has been given exclusively to <= 5 years old children in 3
      paediatric doses since 1997. However, JE incidence remained high, especially
      among children aged 5-9 years. We conducted a model JE immunization programme to
      assess the feasibility and impact of JE vaccine administered to 1-9 year(s)
      children in 3 standard-dose regimen: paediatric doses for children aged <3 years
      and adult doses for those aged >= 3 years. Of the targeted children, 96.2% were
      immunized with >= 2 doses of the vaccine. Compared to the national immunization
      programme, JE incidence rate declined sharply in districts with the model
      programme (11.32 to 0.87 per 100,000 in pre-versus post-vaccination period). The
      rate of reduction was most significant in the 5-9 years age-group. We recommend a
      policy change to include 5-9 years old children in the catch-up immunization
      campaign and administer a 4th dose to those aged 5-9 years, who had received 3
      doses of the vaccine during the first 2-3 years of life.

PMID- 25995737
TI  - Captopril in congenital chloride diarrhoea: a case study.
AB  - An 11 months 22 days old girl presented with a history of watery diarrhoea since
      birth, failure to thrive, and developmental delay. Her diagnosis was congenital
      chloride diarrhoea (CCD) with raised level of chloride (>90 mmol/L) in stool in
      the absence of cystic fibrosis. Management of CCD included replacement of NaCl,
      KCl, and correction of dehydration. Diarrhoea of the patient was resolved with
      Captopril, which was initially provided to the patient for managing heart
      failure. To our knowledge, this is the first reported case of CCD that shows the
      beneficial effect of Captopril. Therefore, we suggest that further study is
      warranted as to the potential for Captopril as additional option in the treatment
      for CCD. We present this case report with the informed consent of the patient's
      guardian. 

PMID- 25995738
TI  - First report of brown widow spider sightings in Peninsular Malaysia and notes on
      its global distribution.
AB  - BACKGROUND: The brown widow spider (Latrodectus geometricus Koch, 1841) has
      colonised many parts of the world from its continent of origin, Africa. By at
      least 1841, the species had successfully established populations in South America
      and has more recently expanded its range to the southern states of North America.
      This highly adaptable spider has been far more successful in finding its niche
      around the world than its famous cousins, the black widow, Latrodectus mactans,
      found in the south-eastern states of North America, and the red-back, Latrodectus
      hasselti, found mostly in Australia, New Zealand and Japan. METHODS: We performed
      an extensive web search of brown widow sightings and mapped the location of each
      sighting using ArcGIS. Specimens reputedly of the species L. geometricus were
      collected at three localities in Peninsular Malaysia. The spiders were identified
      and documented based on an examination of morphological characteristics and DNA
      barcoding. RESULTS: The spiders found in Peninsular Malaysia were confirmed to be
      Latrodectus geometricus based on their morphological characteristics and DNA
      barcodes. We recorded 354 sightings of the brown widow in 58 countries, including
      Peninsular Malaysia. CONCLUSION: Reports from the Americas and the Far East
      suggest a global-wide invasion of the brown widow spider. Herein we report the
      arrival of the brown widow spider in Peninsular Malaysia and provide notes on the
      identification of the species and its recently expanded range.

PMID- 25995739
TI  - Lipid profile and glucose changes after supplementation with astaxanthin: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Many studies have shown that oral supplementation with astaxanthin
      may be a novel potential treatment for inflammation and oxidative stress in
      cardiovascular diseases, but evidence of the effects on lipid profile and glucose
      is still inconclusive. Therefore, we performed a meta-analysis to evaluate the
      efficacy of astaxanthin supplementation on plasma lipid and glucose
      concentrations. MATERIAL AND METHODS: The search included PubMed, Cochrane
      Library, Scopus, and EMBASE (up to November 27, 2014) to identify randomized
      controlled trials (RCTs) investigating the effects of astaxanthin supplementation
      on lipid profile and glucose levels. Two independent reviewers extracted data on
      study characteristics, methods and outcomes. RESULTS: Seven studies meeting
      inclusion criteria with 280 participants were selected for this meta-analysis;
      163 participants were allocated to the astaxanthin supplementation group and 117
      to the control group. A random-effect meta-analysis of data from 7 RCTs (10
      treatment arms) did not show any significant effect of supplementation with
      astaxanthin on plasma concentrations of total cholesterol (weighted mean
      difference (WMD): -1.52 mg/dl, 95% CI: -8.69 to -5.66, p = 0.679), LDL-C (WMD:
      +1.25 mg/dl, 95% CI: -6.70 to +9.21, p = 0.758), HDL-C (WMD: +1.75 mg/dl, 95% CI:
      -0.92 to +4.42, p = 0.199), triglycerides (WMD: -4.76 mg/dl, 95% CI: -21.52 to
      +12.00, p = 0.578), or glucose (WMD: -2.65 mg/dl, 95% CI: -5.84 to +0.54, p =
      0.103). All these effect sizes were robust, and omission of any of the included
      studies did not significantly change the overall estimate. CONCLUSIONS: This meta
      analysis of data from 10 RCT arms did not indicate a significant effect of
      supplementation with astaxanthin on plasma lipid profile, but a slight glucose
      lowering effect was observed. Further, well-designed trials are necessary to
      validate these results.

PMID- 25995740
TI  - Interleukin-1beta (3953/4) C->T polymorphism increases the risk of chronic
      periodontitis in Asians: evidence from a meta-analysis of 20 case-control
      studies.
AB  - INTRODUCTION: To investigate the association of the interleukin-1beta (IL-1beta)
      (3953/4) C->T polymorphism with chronic periodontitis (CP) in Asians. MATERIAL
      AND METHODS: Systematic searches of electronic databases and hand searching of
      references were performed, including PubMed, Embase, the Cochrane Library, and
      the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of the associations.
      Publication bias was tested by Egger's test. Sensitivity analysis was conducted
      by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium
      (HWE). Data analyses were carried out using RevMan 6.0. RESULTS: A meta-analysis
      was performed on 20 published case-control studies, including 1,656 CP cases and
      1,498 healthy controls. The pooled OR was 1.60 (95% CI = 1.02-2.52, p = 0.04) for
      the T allele carriers (TT + CT) compared with CC and 1.60 (95% CI = 1.06-2.42, p
      = 0.02) for T vs. C. Subgroup analysis by country revealed significant risks of
      CP among Indians carrying the T allele (TT vs. CC: OR = 3.88, 95% CI = 1.77-8.50,
      p = 0.0007). CONCLUSIONS: The analysis showed that IL-1beta (3953/4) C->T
      polymorphism probably increases the risk of CP in Asians, and the IL-1beta+3954
      TT genotype may be associated with a strongly increased risk of CP in Indians,
      but not in Chinese.

PMID- 25995741
TI  - A systemic review of randomized controlled studies about prevention with
      pharmacologic agents of adhesion formation in the rat uterine horn model.
AB  - INTRODUCTION: Evaluation of treatment attempts in postoperative adhesion
      formation is pivotal for the prevention of several morbidities including
      infertility, pelvic pain, bowel obstruction, and subsequent intraoperative
      complications. The purpose of this systemic review was to assess the literature
      on the rat uterine horn model for adhesion formation and treatment modalities to
      prevent adhesion in the most frequently used experimental animal model. MATERIAL
      AND METHODS: We performed a systemic review of publications from January 1(st)
      2000 to December 31(st) 2013 via a PubMed search. A high number of agents were
      evaluated for the prevention of postoperative adhesion formation in the rat
      uterine horn model. RESULTS: According to most of the studies, adjuvants such as
      antiinflamatuars, antiestrogens, antioxidants were effective to prevent adhesion
      formation. CONCLUSIONS: Prevention of adhesion formation is pivotal and numerous
      types of agents were described in the literature were summarized in this review.

PMID- 25995742
TI  - Polyunsaturated fatty acids augment tumoricidal action of 5-fluorouracil on
      gastric cancer cells by their action on vascular endothelial growth factor, tumor
      necrosis factor-alpha and lipid metabolism related factors.
AB  - INTRODUCTION: Gastric cancer is the second most common cause of cancer-related
      mortality worldwide. 5-fluorouracil (5-FU) is a commonly used anti-cancer drug.
      Various polyunsaturated fatty acids (PUFAs) are known to have tumoricidal action
      both in vitro and in vivo. Though PUFAs are known to augment the cytotoxic action
      of anti-cancer drugs, the exact mechanism is not clear. MATERIAL AND METHODS: The
      human gastric cancer cell line MGC (undifferentiated) and human gastric cancer
      cell line SGC (semi-differentiated) were either 5-FU alone or a combination of 5
      FU + PUFAs and their proliferation, and ability to secrete tumor necrosis factor
      alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) and lipid
      metabolism-related factors lipoprotein lipase (LPL), peroxisome proliferator
      activated-gamma (PPAR-gamma), and CCAAT enhancer-binding protein (C/EBP) were
      investigated and analyzed. RESULTS: It was noted that combined treatment of 5-FU
      + PUFAs on gastric carcinoma (MGC and SGC) cells produced a significant growth
      inhibitory action compared with either agent alone by inhibiting the production
      of TNF-alpha and VEGF and a simultaneous increase in the expression of LPL, PPAR
      gamma, and C/EBP. CONCLUSIONS: Based on the results of the present study, it is
      concluded that PUFAs enhance the tumoricidal action of the anti-cancer drug 5-FU
      by acting on anti-angiogenic factors and enzymes involved in lipid metabolism.

PMID- 25995743
TI  - Galactosylated poly-L-lysine targeted microbubbles for ultrasound mediated
      antisense c-myc gene transfection in hepatocellular carcinoma cells.
AB  - INTRODUCTION: The aim of the study was to investigate the efficiency of delivery
      and targeted binding of c-myc antisense oligodeoxynucleotide (ASODN) and find a
      novel therapy for hepatic carcinoma. MATERIAL AND METHODS: A targeted ultrasound
      microbubble compound was synthesized to deliver the c-myc ASODN by ultrasound
      targeted microbubble destruction (UTMD) and applied in hepatocellular carcinoma
      cells (HCC) and cancer bearing mice. Lipid microbubbles were conjugated with
      biotinylated galactosylated poly-L-lysine (G-PLL) and SonoVue to target the
      hepatocellular carcinoma SMMC7721 cells with asialoglycoprotein receptors. There
      were four groups in both in vitro and in vivo studies: control group (group A); c
      myc ASODN + G-PLL (CG group, group B); c-myc ASODN + SonoVue (CUS group, group
      C); c-myc ASODN + G-PLL + SonoVue (CGUS group, group D). The expression of c-myc
      mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR),
      and proliferation investigations of the SMMC7721 cells were also performed. In
      addition, the tumor volume was calculated and compared among different groups.
      RESULTS: The level of c-myc mRNA in the three experimental groups was
      significantly lower than that in the control group in vitro (p < 0.05).
      Furthermore, c-myc gene expression was suppressed more strongly in the CGUS group
      compared with other groups in both in vitro and in vivo studies (p < 0.05). In
      addition, ultrasound mediation of targeted microbubbles yielded the highest
      inhibition of tumor growth and cell proliferation among the four groups.
      CONCLUSIONS: The use of a G-PLL targeted microbubble contrast agent combined with
      ultrasound exposure could be a potential method for increasing gene delivery
      efficiency. This technique is a promising nonviral approach that can be used in
      liver cancer.

PMID- 25995744
TI  - Influence of PJ34 on the genotoxicity induced by melphalan in human multiple
      myeloma cells.
AB  - INTRODUCTION: The aim of this study was to evaluate the potential biological
      activity of N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide
      hydrochloride (PJ34) on the genotoxicity induced by melphalan in human multiple
      myeloma cells. MATERIAL AND METHODS: The inhibitory effects of the drugs on the
      growth of RPMI8226 cells were determined by Cell Counting Kit-8 (CCK-8) assay.
      The expression of Fanconi anemia/breast cancer (FA/BRCA) pathway related genes
      was determined by western blot analysis. Cell cycle phase and apoptosis were
      analyzed by flow cytometry. Coadministration of PJ34 and melphalan had additional
      effects on cell cycle distribution and enhanced apoptosis of RPMI8226 cells. PJ34
      plus melphalan inhibited cell-cycle progression, as evidenced by the increased
      proportion of cells in the G2/M phase with the decreasing proportion of cells in
      the G0/1 and S phases. RESULTS: However, no significant synergistic effect of
      PJ34 and melphalan on cell proliferation was observed. These effects were
      accompanied by inhibition of the FA/BRCA pathway by downregulation of Fanconi D2
      (FANCD2) protein expression. The results showed that treatment with 60 umol/l of
      PJ34 previously to melphalan administration increased cell apoptosis.
      Pretreatment also caused cell cycle arrest. CONCLUSIONS: This study suggests that
      enhancement of melphalan efficacy may be best achieved by the poly(ADP-ribose)
      polymerase-1 (PARP-1) inhibitor PJ34. The effects of PJ34 are associated with
      inhibition of the FA/BRCA pathway, increased apoptosis percentage, and G2/M cell
      cycle arrest. Administration of PJ34 has been shown to protect DNA from damage
      induced by melphalan. This corroborates the biological activities of PJ34 and
      points to the need for further studies.

PMID- 25995745
TI  - Efficacy of low dose temozolomide in combination with bortezomib in U87 glioma
      cells: a flow cytometric analysis.
AB  - INTRODUCTION: Maximizing responses of malignant gliomas is hampered by resistance
      to temozolomide (TMZ). Increasing efficacy but not toxicity is a key issue when
      testing drug combinations. The antimyeloma agent bortezomib (BZ) has shown
      promising results in vitro and is currently being tested in glioblastoma (GBM)
      patients. In this study we investigate whether reduction of TMZ dosage is
      feasible without compromising the antitumor effect of TMZ-BZ combination.
      MATERIAL AND METHODS: U87 GBM cells were treated with increasing doses of TMZ (1,
      10, 100, 1000 uM), BZ (0.001, 0.01, 0.1, 1) and the combination during a 48-hour
      period, and apoptotic or/and necrotic cell death was evaluated by flow cytometry.
      RESULTS: Bortezomib alone at a dose as low as 0.001 uM markedly induced cell
      death, particularly late apoptosis, to a level which was comparable with high TMZ
      dosage. For combination treatments, the dose of 0.1 uM BZ, which was more potent
      than the maximal dose of TMZ (1000 uM), was chosen to be added to increasing TMZ
      concentrations. The combination of 0.1 BZ uM BZ with low doses of TMZ (1, 10 uM)
      further increased the cell death rate in an additive manner, at levels higher
      than those induced by high doses of TMZ monotherapy (100, 1000 uM). CONCLUSIONS:
      Efficacy of TMZ-BZ combination is feasible with low doses of TMZ in vitro.

PMID- 25995746
TI  - Does joint line elevation after revision knee arthroplasty affect tibio-femoral
      kinematics, contact pressure or collateral ligament lengths? An in vitro
      analysis.
AB  - INTRODUCTION: Correct restoration of the joint line is generally considered as
      crucial when performing total knee arthroplasty (TKA). During revision knee
      arthroplasty however, elevation of the joint line occurs frequently. The general
      belief is that this negatively affects the clinical outcome, but the reasons are
      still not well understood. MATERIAL AND METHODS: In this cadaveric in vitro study
      the biomechanical consequences of joint line elevation were investigated using a
      previously validated cadaver model simulating active deep knee squats and passive
      flexion-extension cycles. Knee specimens were sequentially tested after total
      knee arthroplasty with joint line restoration and after 4 mm joint line
      elevation. RESULTS: The tibia rotated internally with increasing knee flexion
      during both passive and squatting motion (range: 17 degrees  and 7 degrees 
      respectively). Joint line elevation of 4 mm did not make a statistically
      significant difference. During passive motion, the tibia tended to become
      slightly more adducted with increasing knee flexion (range: 2 degrees ), while it
      went into slighlty less adduction during squatting (range: -2 degrees ). Neither
      of both trends was influenced by joint line elevation. Also anteroposterior
      translation of the femoral condyle centres was not affected by joint line
      elevation, although there was a tendency for a small posterior shift (of about 3
      mm) during squatting after joint line elevation. In terms of kinetics, ligaments
      lengths and length changes, tibiofemoral contact pressures and quadriceps forces
      all showed the same patterns before and joint line elevation. No statistically
      significant changes could be detected. CONCLUSIONS: Our study suggests that joint
      line elevation by 4 mm in revision total knee arthroplasty does not cause
      significant kinematic and kinetic differences during passive flexion/extension
      movement and squatting in the tibio-femoral joint, nor does it affect the
      elongation patterns of collateral ligaments. Therefore, clinical problems after
      joint line elevation are probably situated in the patello-femoral joint or caused
      by joint line elevation of more than 4 mm.

PMID- 25995747
TI  - Incidence and risk predictors for osteonecrosis of the jaw in cancer patients
      treated with intravenous bisphosphonates.
AB  - INTRODUCTION: The aim of this study was to establish the incidence of
      bisphosphonate-related osteonecrosis of the jaws (BRONJ) in oncologic patients
      and to determine risk predictors with respect to this condition. MATERIAL AND
      METHODS: This retrospective review included 197 oncologic patients treated from
      January 2005 to December 2010 with administration of bisphosphonates (BPs) as
      part of management. Sex, age, type of cancer diagnosed, period of substantial
      disease, oral surgery, type of bisphosphonate, number of doses, and cases of
      BRONJ diagnosis were recorded. The cumulative incidence and incidence rate of
      BRONJ were calculated. The factors that influenced BRONJ were assessed with
      multivariate logistic regression and with estimations of 95% confidence intervals
      and odd ratios. Values of p <= 0.05 were considered significant. RESULTS: The
      BRONJ appeared in 9.64% of patients. The BRONJ incidence rate was 1 in 28
      patients per year of BP treatment. Logistic regression showed that the odds of
      osteonecrosis increased 1.0172-fold with each given dose of BP. The BRONJ risk
      with zoledronate was 5-fold higher than that with pamidronate or ibandronate. The
      risk of BRONJ increased by 40-fold after dental surgery. CONCLUSIONS: Period of
      BP administration and type of BP used are important risk predictors for the
      development of BRONJ in oncologic patients treated with intravenous
      administration of these drugs. Patient-related factors are dental or periodontal
      events connected with need for oral surgery.

PMID- 25995748
TI  - Combined autologous bone marrow mononuclear cell and gene therapy as the last
      resort for patients with critical limb ischemia.
AB  - INTRODUCTION: Our study was designed to investigate the safety and efficacy of
      combined autologous bone marrow mononuclear cell (MNC) and gene therapy in
      comparison to conventional drug therapy in patients with critical limb ischemia
      (CLI). MATERIAL AND METHODS: Thirty-two patients with CLI persisting for 12-48
      months (average time 27.5 months) were randomized into 2 groups, each group
      consisting of 16 patients. In the first group, administration of autologous bone
      marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed.
      The patients from the second group were treated pharmacologically with
      pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was
      performed before and finally 3 months after treatment. The pain was evaluated
      using the Visual Analog Scale (VAS) before and after 3 months. RESULTS: Ankle
      brachial index improved significantly from 0.29 +/-0.21 to 0.52 +/-0.23 (p <
      0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1.
      In this group angiography showed the development of collateral vessels. Ischemic
      ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not
      improve in any patient; moreover the complete healing of skin ulcers was not
      found in any of the patients of this group. Amputation was performed in 4 (25.0%)
      patients in group 1, and in 8 patients (50%) from group 2. CONCLUSIONS: These
      data after 3-month follow-up indicate that intramuscular injection of MNC
      combined with gene therapy in patients with chronic CLI is safe, and a more
      feasible and effective method of treatment than the conventional therapy.
      However, both therapies are limited by the degree of microcirculation damage.

PMID- 25995749
TI  - Role of immunosuppressive therapy and predictors of therapeutic effectiveness and
      renal outcome in IgA nephropathy with proteinuria.
AB  - INTRODUCTION: The aim of the study was to analyze the role of immunosuppressive
      therapy and identify independent predictors of therapeutic effectiveness and
      outcome in IgA nephropathy (IgAN) patients with proteinuria. MATERIAL AND
      METHODS: Two hundred and six IgAN patients with proteinuria (1-3.5 g/day) were
      included between January 2005 and December 2011, and divided into two groups:
      group A (n = 125), receiving renin-angiotensin system blockade therapy alone; and
      group B (n = 81), combining the above with immunosuppressive therapy. The
      clinicopathological features, response and safety were recorded. In univariate
      and multivariate models, the factors that influence response to therapy and renal
      outcome, especially pathologic features, were analyzed. RESULTS: The patients in
      group B presented more severe proteinuria and hypoalbuminemia with more severe
      hematuria (p < 0.05) but no significant difference in the pathologic changes
      compared with group A. After follow-up, the response rate was higher in group B
      than in group A (p < 0.001). No pathologic feature or clinical parameter apart
      from steroid therapy (HR = 0.500, 95% CI: 0.304-0.821, p = 0.006) was strongly
      associated with therapeutic effectiveness. Endocapillary hypercellularity (HR =
      2.849, 95% CI: 1.244-6.524, p = 0.013) seemed to be an independent predictor of
      poor response to steroid therapy. The renal survival rate was not significantly
      different between the two groups (p = 0.074). Estimated glomerular filtration
      rate at baseline may be an independent predictor of renal outcome. CONCLUSIONS:
      Steroid therapy could be an effective therapy in proteinuric IgAN patients, and
      endocapillary hypercellularity seemed to predict poor response to steroid. Renal
      function at baseline rather than treatment strategies and pathologic features may
      be independently associated with renal survival.

PMID- 25995750
TI  - Renal access through the inferior calyx is associated with higher risk of severe
      bleeding after percutaneous nephrolithotomy.
AB  - INTRODUCTION: Hemorrhage is a major complication after percutaneous
      nephrolithotomy (PCNL). In the current study, we analyzed the risk factors for
      severe bleeding after PCNL. MATERIAL AND METHODS: Medical records of 982
      consecutive patients undergoing PCNL at the Department of Urology, the Third
      Xiangya Hospital, were reviewed. The type of stone included: solitary (n = 471),
      multiple (n = 192) and staghorn (n = 319). 139 patients had renal stones of
      solitary kidney or functional solitary kidney. The puncture site was the inferior
      calyx in 246 cases, the middle calyx in 651 cases, and the upper calyx in the
      remaining 85 cases. RESULTS: The success rate (complete removal of the stone) was
      92.8%, 73.4%, and 80.9% for solitary, multiple and staghorn stones, respectively.
      Severe bleeding occurred in 3.25% (8/246) of the cases with inferior calyx
      access, and 0.3% (2/651) in cases with middle calyx access. No severe bleeding
      occurred in patients with upper calyx access. The bleeding was controlled
      successfully with focal embolization under angiography in all 10 cases.
      CONCLUSIONS: Severe postoperative bleeding after PCNL is associated with renal
      puncture via the inferior calyx, multiple renal stones and solitary kidney
      stones.

PMID- 25995751
TI  - Serum leptin levels in gastric cancer patients and the relationship with insulin
      resistance.
AB  - INTRODUCTION: Serum leptin levels have been examined in various cancers, with
      conflicting results. However, there is limited information regarding serum leptin
      levels and insulin resistance in gastric cancer patients. Therefore, we aimed to
      investigate serum leptin levels, performance status, insulin levels and insulin
      resistance in patients with gastric cancer. In addition, we examined the
      relationship between these measurements and leptin levels. MATERIAL AND METHODS:
      Thirty-nine patients with gastric cancer and 30 control subjects were enrolled in
      the study. Serum leptin, total protein, albumin, growth hormone, insulin and
      glucose levels were measured. The homeostasis model assessment (HOMA) was used to
      assess insulin resistance. RESULTS: Serum levels of insulin, glucose and growth
      hormone and insulin resistance were significantly lower in gastric cancer
      patients than controls (p < 0.05 for all). In the Pearson correlation analysis,
      insulin resistance was found to be significantly correlated with serum leptin
      levels in gastric cancer patients (r = 0.320, p = 0.047). We observed a
      significant negative correlation between performance status and insulin
      resistance in patients with cachexia (r = -0.512, p = 0.030), while no
      association was found in non-cachectic patients. CONCLUSIONS: We concluded that
      serum leptin levels are significantly lower in gastric cancer patients. In
      addition, gastric cancer patients have decreases in insulin levels, insulin
      resistance and growth hormone levels. This study found a positive association
      between serum leptin levels and insulin resistance. Moreover, there is a negative
      association between serum leptin levels and growth hormone levels. Thus, low
      insulin and growth hormone levels may suppress the production of leptin in
      gastric cancer patients.

PMID- 25995752
TI  - Is faecal calprotectin equally useful in all Crohn's disease locations? A
      prospective, comparative study.
AB  - INTRODUCTION: There are data suggesting that the diagnostic usefulness of faecal
      calprotectin (FC) may vary depending on the Crohn's disease (CD) location. The
      aim of the study was to compare the diagnostic usefulness of FC in CD patients
      with different disease locations. MATERIAL AND METHODS: We prospectively enrolled
      120 CD patients in the study. Disease activity was assessed by using Crohn's
      Disease Activity Index (CDAI), biochemical markers, and endoscopic and
      radiographic methods. Faecal calprotectin concentration was assessed in single
      stool samples by using the ELISA method. RESULTS: Among all patients, 54 (45%)
      had ileocolonic CD location, 44 (36.5%) had isolated small bowel location, and 22
      (18.5%) had colonic CD location. FC correlated significantly with C-reactive
      protein concentration and endoscopic and radiographic activity among patients
      with isolated small bowel CD (p = 0.03, r = 0.32; p < 0.0001, r = 0.78; p = 0.03,
      r = 0.35; respectively) and with C-reactive protein and endoscopic activity in
      isolated colonic CD (p = 0.0009, r = 0.7; p = 0.0002, r = 0.78; respectively).
      CDAI and inflammatory biochemical markers did not correlate with endoscopic and
      radiographic assessment in small bowel CD. In patients with ileocolonic CD, FC
      correlated significantly with endoscopy (p = 0.006, r = 0.5), radiographic
      assessment (p = 0.04, r = 0.3), CDAI (p = 0.0006, r = 0.5) and the majority of
      biochemical markers. CONCLUSIONS: Faecal calprotectin is a useful diagnostic
      marker in all CD patients. Although its usefulness in small bowel CD seems to be
      the lowest, it should be utilized particularly in this disease location because
      of the lack of other reliable, non-invasive diagnostic methods.

PMID- 25995753
TI  - Ondansetron-droperidol combination vs. ondansetron or droperidol monotherapy in
      the prevention of postoperative nausea and vomiting.
AB  - INTRODUCTION: Laparoscopic cholecystectomy is associated with a high incidence of
      postoperative nausea and vomiting. In this study we investigated comparatively
      the efficacy of combination therapy with ondansetron plus droperidol versus
      monotherapy with each agent alone in preventing postoperative nausea and vomiting
      following elective laparoscopic cholecystectomy. MATERIAL AND METHODS: One
      hundred twenty-seven patients who underwent elective laparoscopic cholecystectomy
      under general anesthesia were included in the study, and assigned to one of the
      following three groups according to the antiemetic drug given intravenously at
      the end of the surgery: droperidol 1.25 mg in group D, ondansetron 4 mg in group
      O, and a combination of droperidol and ondansetron at the doses mentioned above
      in group D + O. Incidence of postoperative nausea and vomiting, and doses of
      given rescue antiemetics were recorded during the first postoperative day. The
      total drug cost per patient spent for postoperative nausea and vomiting
      management (including prophylactic antiemetics plus rescue postoperative
      antiemetics) was calculated. RESULTS: Combination therapy significantly reduced
      postoperative nausea and vomiting at 30 min, 3 h and 6 h after surgery compared
      with group D (p < 0.01 for all time points) and O (p < 0.01 at 30 min, p < 0.05
      at 3 h) and required less rescue antiemetic treatment (p < 0.01). Total
      antiemetic cost analyses revealed no significant differences among the three
      groups (p > 0.05). CONCLUSIONS: Pretreatment with ondansetron plus droperidol is
      more effective than monotherapy in preventing postoperative nausea and vomiting
      following laparoscopic cholecystectomy, without increasing the cost
      comparatively.

PMID- 25995754
TI  - The influence of steroid receptor status on the cardiotoxicity risk in HER2
      positive breast cancer patients receiving trastuzumab.
AB  - INTRODUCTION: Expression of steroid receptors and HER2 overexpression in breast
      cancer cells are predictive and prognostic factors. Overexpression of HER2 allows
      the use of immunotherapy, in which the most serious side effect is
      cardiotoxicity. The aim of this study was to evaluate the influence of steroid
      receptor status on cardiotoxicity risk in HER2 breast cancer patients receiving
      trastuzumab both in adjuvant treatment and in the case of disease dissemination.
      This study also assessed well-known cardiac risk factors. MATERIAL AND METHODS:
      The study was conducted on 166 patients who received immunotherapy in the
      Clinical and Experimental Oncology Department, between the years 2006 and 2012.
      RESULTS: A predisposition to cardiac side effects (13% vs. 5%) in patients with
      negative steroid receptor status was observed (p = 0.08). The decrease of left
      ventricular ejection fraction (LVEF) (12% vs. 0) and cardiac adverse side effects
      (2% vs. 0) were detected only in ER-/PR- patients but without statistical
      significance. Discontinuation of therapy because of cardiotoxicity was associated
      with negative receptor status (33% vs. 7%) (p = 0.019). Irrespective of steroid
      receptor status, older age of patients (p = 0.009) and previous radiotherapy to
      the left side of the chest (p = 0.02) were associated with the occurrence of
      cardiotoxicity and decrease of LVEF. In patients who received previous
      anthracycline-based chemotherapy, acute cardiac side effects were observed
      significantly more often (p = 0.01). CONCLUSIONS: There was no influence of
      steroid receptor status on the cardiac side effects. Breast cancer type
      containing Erb-B2 overexpression was associated with predisposition to
      cardiotoxicity. The results require confirmation in a larger group of patients.

PMID- 25995755
TI  - Expression of bone morphogenetic protein-2 and -7 in urinary bladder cancer
      predicts time to tumor recurrence.
AB  - INTRODUCTION: Urinary bladder cancer patients who have undergone transurethral
      resection of bladder tumor (TURBT) are at risk of recurrence. This study aims to
      correlate the level of bone morphogenetic protein (BMP) expression with
      urothelial carcinoma invasiveness, TNM stage and time to recurrence after TURBT.
      MATERIAL AND METHODS: In 33 specimens of healthy transitional epithelium and 42
      of urothelial carcinoma, BMP2, BMP4 and BMP7 expression was determined by real
      time polymerase chain reaction. Patients who underwent TURBT were followed up for
      1 year. RESULTS: BMP2 and BMP7 were downregulated in infiltrating urothelial
      carcinoma, the relative expression being 0.76 (p = 0.04) and 0.28 (p = 0.025)
      respectively, while BMP4 was downregulated in non-invasive tumors. High
      expression of BMP2 and BMP7 correlated with prolonged time to recurrence (log
      rank: p = 0.01 and p = 0.03 respectively). CONCLUSIONS: Low expression of BMP2
      and BMP7 is associated with shorter time to recurrence. The BMP expression levels
      are not indicative of tumor stage.

PMID- 25995757
TI  - Arthroscopic posterior cruciate ligament reconstruction with allograft versus
      autograft.
AB  - INTRODUCTION: The aim of the study was to compare and analyze retrospectively the
      outcomes of arthroscopic posterior cruciate ligament reconstruction with
      autograft versus allograft. MATERIAL AND METHODS: Seventy-one patients who
      underwent arthroscopic posterior cruciate ligament reconstruction with an
      autograft or allograft met our inclusion criteria. There were 36 patients in the
      autograft group and 35 patients in the allograft group. All the patients were
      evaluated by physical examination and a functional ligament test. Comparative
      analysis was done in terms of operation time, incision length, fever time,
      postoperative infection rate, incidence of numbness and dysesthesia around the
      incision, as well as a routine blood test. RESULTS: The average follow-up of the
      autograft group was 3.2 +/-0.2 years and that of the allograft group was 3.3 +/
      0.6 years; there was no significant difference (p > 0.05). No differences existed
      in knee range of motion, Lysholm scores, International Knee Documentation
      Committee standard evaluation form and Tegner activity score at final follow-up
      (p > 0.05), except that patients in the allograft group had a shorter operation
      time and incision length and a longer fever time (p < 0.05). We found a
      difference in posterior drawer test and KT-2000 arthrometer assessment (p <
      0.05). The posterior tibia displacement averaged 3.8 +/-1.5 mm in the autograft
      group and 4.8 +/-1.7 mm in the allograft group (p < 0.05). The incidence of
      numbness and dysesthesia around the incision in the autograft group was higher
      than that in the allograft group (p < 0.05). There was no infection
      postoperatively. The white blood cells and neutrophils in the allograft group
      increased more than those in the autograft group postoperatively (p < 0.05).
      CONCLUSIONS: Both groups of patients had satisfactory outcomes after the
      operation. However, in the instrumented posterior laxity test, the autograft gave
      better results than the allograft. No differences in functional scores were
      found.

PMID- 25995756
TI  - Urinary microbiota in patients with prostate cancer and benign prostatic
      hyperplasia.
AB  - INTRODUCTION: Inflammation is associated with promotion of the initiation of
      various malignancies, partly due to bacterial infection-induced
      microenvironmental changes. However, the exact association between microbiota in
      urine, seminal fluid and the expressed prostatic secretions and benign prostatic
      hypertrophy and prostate cancer is not clear. MATERIAL AND METHODS: In the
      present study, we investigated the type of microbiota in the expressed prostatic
      secretions (EPS) of patients with prostate cancer and benign prostatic
      hyperplasia (BPH) by the polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE) method using universal bacterial primers. In order to
      understand the possible association between various bacteria and prostate cancer,
      quantitative real-time PCR assay was performed to quantify the amount of strains
      of bacteria in urine, EPS and seminal fluid. RESULTS: The prostate cancer group
      had a significantly increased number of Bacteroidetes bacteria,
      Alphaproteobacteria, Firmicutes bacteria, Lachnospiraceae, Propionicimonas,
      Sphingomonas, and Ochrobactrum, and a decrease in Eubacterium and Defluviicoccus
      compared to the BPH group. The number of Escherichia coli in the prostate cancer
      group was significantly decreased in urine and increased in the EPS and seminal
      fluid, while the number of Enterococcus was significantly increased in the
      seminal fluid with little change in urine and EPS. CONCLUSIONS: Based on these
      results, we suggest that there are significant changes in the microbial
      population in EPS, urine and seminal fluid of subjects with prostate cancer and
      BPH, indicating a possible role for these bacteria in these two conditions.

PMID- 25995758
TI  - Evaluation of 37,438 consecutive cervical smear results in the Turkish
      population.
AB  - INTRODUCTION: Retrospective evaluation of cervical smear results of women who
      attended our gynecology policlinics with various symptoms and discussion of the
      results in the light of the literature. MATERIAL AND METHODS: We performed a
      retrospective investigation on 37,438 Pap smear results of women who attended our
      hospital between January 2011 and December 2012 with a variety of symptoms.
      RESULTS: Average patient age was 43 (18-83) years. Of the Pap smear results
      analyzed, in 21,503 (57.4%) findings were within normal limits, while 153 (0.41%)
      showed epithelial cell abnormalities and 15,358 (41%) showed inflammation. Four
      hundred and twenty-four (1.1%) cases were reported to have inadequate Pap smear
      samples for evaluation. Of the epithelial cell abnormalities, 136 (88.8%) were
      squamous cell abnormalities and 17 (11.1%) were glandular cell abnormalities.
      Atypical squamous cells of unknown significance (ASCUS) were reported for 117
      (0.3%) Pap smears, while other epithelial abnormalities included atypical
      glandular cells of unknown significance (AGUS) in 17 (0.05%) cases, low-grade
      squamous intraepithelial lesion (LSIL) in 8 (0.02%) cases, atypical squamous
      cells with possible high grade lesion (ASC-H) in 8 (0.02%) cases and high-grade
      squamous intraepithelial lesion (HSIL) in 3 (0.008%) cases. CONCLUSIONS: Public
      awareness should be raised on the importance of Pap smear testing repeated at
      appropriate intervals in the prevention and early diagnosis of cervical cancer.
      Health education should become more widespread, and the importance of screening
      programs and regular check-ups should be emphasized more often on this issue in
      the media.

PMID- 25995759
TI  - Improvement of hepatic bioavailability as a new step for the future of statin.
AB  - Statins (HMG-CoA reductase inhibitors) are a group of highly efficient
      pharmacological agents used for reducing blood cholesterol level and
      prevention/treatment of cardiovascular disease. Adverse reactions during statin
      treatment affect quite significant numbers of patients (reportedly from 5% to
      20%), with more side effects occurring at higher doses. Reduced statin dosing can
      be achieved by improved bioavailability of statins, which is fairly low due to
      poor aqueous solubility, low permeability and high molecular weight of some
      members of the statin family. Moreover, since hepatic cholesterologenesis is a
      main target of statin action and extrahepatic inhibition of HMG-CoA reductase has
      no effect on plasma lipids, hepatic bioavailability, in our opinion, becomes a
      new important modality of statins maximizing their potential effect on the plasma
      lipid profile and diminishing their extrahepatic toxicity. Therefore efficient
      delivery systems of statins into hepatocytes need to be developed and introduced.
      Uses of nano-emulsifying statin delivery systems which may include vectors of
      intrahepatic transport, in particular lycopene, are discussed. As a proof of
      concept, some preliminary results revealing the effect of a lycopene-containing
      nanoformulation of simvastatin (designated as Lyco-Simvastatin) on LDL in mildly
      hypercholesterolemic patients are shown. 

PMID- 25995760
TI  - The impact of nutrition in urogenital cancers.
AB  - Prostate, bladder and kidney cancers remain the most common cancers of the
      urinary tract. Despite improved primary prevention, detection and treatment, the
      incidence of age-related cancers of the urinary tract is likely to rise as a
      result of global population ageing. An association of diet with prostate, bladder
      and kidney carcinogenesis is plausible since the majority of metabolites,
      including carcinogens, are excreted through the urinary tract. Moreover, large
      regional differences in incidence rates of urologic tumours exist throughout the
      world. These rates change when people relocate to different geographic areas,
      which is suggestive of a strong environmental influence. As a result of these
      observations, numerous studies have been conducted to assess the effects of diet
      and nutritional status in kidney, bladder and prostate carcinogenesis. Here, we
      review the literature assessing the effect of diet and nutritional status on
      urological cancer risk, which has attracted the most interest. 

PMID- 25995761
TI  - The trigeminocardiac reflex - a comparison with the diving reflex in humans.
AB  - The trigeminocardiac reflex (TCR) has previously been described in the literature
      as a reflexive response of bradycardia, hypotension, and gastric hypermotility
      seen upon mechanical stimulation in the distribution of the trigeminal nerve. The
      diving reflex (DR) in humans is characterized by breath-holding, slowing of the
      heart rate, reduction of limb blood flow and a gradual rise in the mean arterial
      blood pressure. Although the two reflexes share many similarities, their
      relationship and especially their functional purpose in humans have yet to be
      fully elucidated. In the present review, we have tried to integrate and elaborate
      these two phenomena into a unified physiological concept. Assuming that the TCR
      and the DR are closely linked functionally and phylogenetically, we have also
      highlighted the significance of these reflexes in humans. 

PMID- 25995762
TI  - Quercetin protects against lipopolysaccharide-induced acute lung injury in rats
      through suppression of inflammation and oxidative stress.
AB  - INTRODUCTION: Acute lung injury (ALI) is an acute inflammatory disease
      characterized by excess production of inflammatory factors in lung tissue.
      Quercetin, a herbal flavonoid, exhibits anti-inflammatory and anti-oxidative
      properties. This study was performed to assess the effects of quercetin on
      lipopolysaccharide (LPS)-induced ALI. MATERIAL AND METHODS: Sprague-Dawley rats
      were randomly divided into 3 groups: the control group (saline alone), the LPS
      group challenged with LPS (Escherichia coli 026:B6; 100 ug/kg), and the quercetin
      group pretreated with quercetin (50 mg/kg, by gavage) 1 h before LPS challenge.
      Bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected 6 h
      after LPS administration. Histopathological and biochemical parameters were
      measured. RESULTS: The LPS treatment led to increased alveolar wall thickening
      and cellular infiltration in the lung, which was markedly prevented by quercetin
      pretreatment. Moreover, quercetin significantly (p < 0.05) attenuated the
      increase in the BALF protein level and neutrophil count and lung wet/dry weight
      ratio and myeloperoxidase activity in LPS-challenged rats. The LPS exposure
      evoked a 4- to 5-fold rise in BALF levels of tumor necrosis factor-alpha and
      interleukin-6, which was significantly (p < 0.05) counteracted by quercetin
      pretreatment. Additionally, quercetin significantly (p < 0.05) suppressed the
      malondialdehyde level and increased the activities of superoxide dismutase,
      catalase, and glutathione peroxidase in the lung of LPS-treated rats.
      CONCLUSIONS: Quercetin pretreatment effectively ameliorates LPS-induced ALI,
      largely through suppression of inflammation and oxidative stress, and may thus
      have therapeutic potential in the prevention of this disease.

PMID- 25995763
TI  - Erythropoietin promotes peripheral nerve regeneration in rats by upregulating
      expression of insulin-like growth factor-1.
AB  - INTRODUCTION: Erythropoietin (EPO) has been shown to have beneficial effects on
      peripheral nerve damage, but its mechanism of action remains incompletely
      understood. In this study we hypothesized that EPO promotes peripheral nerve
      repair via neurotrophic factor upregulation. MATERIAL AND METHODS: Thirty adult
      male Wistar rats were employed to establish a sciatic nerve injury model. They
      were then randomly divided into two groups to be subjected to different
      treatment: 0.9% saline (group A) and 5000 U/kg EPO (group B). The walking
      behavior of rats was evaluated by footprint analysis, and the nerve regeneration
      was assessed by electron microscopy. The expression of insulin-like growth factor
      1 (IGF-1) in the injured sciatic nerves was detected by immunohistochemical
      analysis. RESULTS: Compared to saline treatment, EPO treatment led to the growth
      of myelin sheath, the recovery of normal morphology of axons and Schwann cells,
      and higher density of myelinated nerve fibers. Erythropoietin treatment promoted
      the recovery of SFI in the injured sciatic nerves. In addition, EPO treatment led
      to increased IGF-1 expression in the injured sciatic nerves. CONCLUSIONS:
      Erythropoietin may promote peripheral nerve repair in a rat model of sciatic
      nerve injury through the upregulation of IGF-1 expression. These findings reveal
      a novel mechanism underlying the neurotrophic effects of EPO.

PMID- 25995764
TI  - Supportive features of a new hybrid scaffold for urothelium engineering.
AB  - INTRODUCTION: Different clinical conditions can compromise the urinary bladder
      function and structure. Routine regenerative practices in urology for bladder
      augmentation have been associated with diverse side effects. The internal lining
      of the bladder, the urothelium, plays an integral role in normal bladder
      function. Tissue engineering has provided novel therapeutic strategies through
      scaffolding and cell transplantation. Nano-scale surface features of scaffolds
      are valuable parameters for enhancement of cell behavior and function. MATERIAL
      AND METHODS: We fabricated a new hybrid scaffold of poly E-caprolactone (PCL) and
      poly-L-lactide acid (PLLA) using an electrospinning system to exploit each
      polymer's advantages at nano-scale in the same scaffold. Dog urothelial cells
      were isolated, characterized by immunocytochemistry, and expanded for loading on
      the scaffold. Cell viability and proliferation on the scaffold surface were
      assessed by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. Furthermore, cytoarchitecture, distribution and detailed morphology of
      cells, and expression of cell specific markers were examined using hematoxylin
      and eosin (H + E) staining, scanning electron microscopy (SEM), and
      immunohistochemistry, respectively. RESULTS: According to MTT results, the
      scaffold did not exert any cytotoxic effect, and also supported cell
      proliferation and viability for 14 days of culture, which led to a significant
      increase in the number of cells. Scanning electron microscopy images revealed
      evenly distributed and normal appearing colonies of urothelial cells. A well
      defined layer of cells was observed using H + E staining, which preserved their
      markers (pan-cytokeratin and uroplakin III) while growing on the scaffold.
      CONCLUSIONS: Our findings confirmed favorable properties of PCL/PLLA regarding
      biocompatibility and applicability for upcoming new methods of bladder
      augmentation and engineering.

PMID- 25995765
TI  - Chronic kidney disease in patients with significant left main coronary artery
      disease qualified for coronary artery bypass graft operation.

PMID- 25995766
TI  - Non-typhoidal Salmonella abscess in a patient with a large thymoma: a rare
      presentation and review of the literature.

PMID- 25995767
TI  - Biological drugs for inducing remission in patients with Crohn's disease:
      determining statistical equivalence according to evidence-based methods.

PMID- 25995768
TI  - Pulmonary arteriovenous malformation mimicking a pulmonary tumour on (18)F
      fluorodeoxyglucose positron-emission tomography/computed tomography.

PMID- 25995769
TI  - Efficient synthesis and antimicrobial evaluation of some Mannich bases from 2
      arylidine-1-thia-4-azaspiro[4.5]decan-3-ones.
AB  - BACKGROUND: Thiazolidinone, has been employed in the preparation of different
      important drugs required for treatment of inflammations, bacterial infections,
      and hypertension. Mannich bases have been shown to exhibit diverse biological
      activities, such as antibacterial, and antifungal activities. Spiroheterocycles
      including thiazolidine moiety have antimicrobial activity. RESULTS: In this
      study, a novel, rapid, and efficient protocol is developed for the synthesis of
      various 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones using sodium
      dodecylbenzene sulfonate (DBSNa) as an inexpensive and readily available reagent
      in acetic acid at room temperature. High yields, easy work-up, and short reaction
      times are advantages of this procedure. The synthesized arylidines were undergone
      Mannich reaction with formaldehyde and secondary amines in absolute ethanol at
      room temperature to afford the corresponding N-Mannich bases. All prepared
      Mannich bases were evaluated for their antimicrobial activity. CONCLUSIONS: Good
      activity was noted for Mannich bases from 2-arylidine-1-thia-4-azaspiro[4.5]decan
      3-ones, with some members recorded higher antimicrobial activity. Graphical
      abstractSynthesis of Mannich bases of 2-arylidine-1-thia-4-azaspiro[4.5]decan-3
      ones.

PMID- 25995771
TI  - Is calprotectin a novel biomarker of neuroinflammation in diabetic periferal
      neuropathy?
AB  - BACKGROUND: In the present study, we aimed to investigate serum calprotectin
      levels in patients with diabetic peripheral neuropathy, and possible role of this
      molecule in the disease pathogenesis. METHOD: Twenty nine patients with diabetic
      peripheral neuropathy, 30 type 2 diabetic patients without neuropathy, and 40
      healthy controls were enrolled in the study. Fasting plasma glucose (FPG), high
      density lipoprotein- cholesterol (HDL-C), low-density lipoprotein- cholesterol
      (LDL-C), total cholesterol, triglyceride, HbA1c, calprotectin and hsCRP levels
      were measured in diabetic and healthy control groups. RESULTS: Serum calprotectin
      and hsCRP levels were significantly higher in patients with and without
      neuropathy than healthy controls (p < 0.001, p = 0.017, p < 0.001 and p = 0.001,
      respectively). Serum calprotectin and hsCRP levels were higher in diabetics with
      neuropathy than the ones without (p = 0.021 and p < 0.001, respectively). The
      positive correlation was detected between calprotectin levels and hsCRP and HbA1c
      in Spearman correlation analysis (r = 0.510, p < 0.001; r = 0.437, p < 0.001
      respectively). The results of multiple logistic regression analysis demonstrated
      the important association between neuropathy development and hsCRP and serum
      calprotectin levels in diabetic individuals. CONCLUSION: Seum calprotectin levels
      were increased in diabetic peripheral neuropathy. It may have a role in the
      pathogenesis of the disease.

PMID- 25995770
TI  - Drosophila Cyclin G and epigenetic maintenance of gene expression during
      development.
AB  - BACKGROUND: Cyclins and cyclin-dependent kinases (CDKs) are essential for cell
      cycle regulation and are functionally associated with proteins involved in
      epigenetic maintenance of transcriptional patterns in various developmental or
      cellular contexts. Epigenetic maintenance of transcription patterns, notably of
      Hox genes, requires the conserved Polycomb-group (PcG), Trithorax-group (TrxG),
      and Enhancer of Trithorax and Polycomb (ETP) proteins, particularly well studied
      in Drosophila. These proteins form large multimeric complexes that bind chromatin
      and appose or recognize histone post-translational modifications. PcG genes act
      as repressors, counteracted by trxG genes that maintain gene activation, while
      ETPs interact with both, behaving alternatively as repressors or activators.
      Drosophila Cyclin G negatively regulates cell growth and cell cycle progression,
      binds and co-localizes with the ETP Corto on chromatin, and participates with
      Corto in Abdominal-B Hox gene regulation. Here, we address further implications
      of Cyclin G in epigenetic maintenance of gene expression. RESULTS: We show that
      Cyclin G physically interacts and extensively co-localizes on chromatin with the
      conserved ETP Additional sex combs (ASX), belonging to the repressive PR-DUB
      complex that participates in H2A deubiquitination and Hox gene silencing.
      Furthermore, Cyclin G mainly co-localizes with RNA polymerase II phosphorylated
      on serine 2 that is specific to productive transcription. CycG interacts with
      Asx, PcG, and trxG genes in Hox gene maintenance, and behaves as a PcG gene.
      These interactions correlate with modified ectopic Hox protein domains in
      imaginal discs, consistent with a role for Cyclin G in PcG-mediated Hox gene
      repression. CONCLUSIONS: We show here that Drosophila CycG is a Polycomb-group
      gene enhancer, acting in epigenetic maintenance of the Hox genes Sex combs
      reduced (Scr) and Ultrabithorax (Ubx). However, our data suggest that Cyclin G
      acts alternatively as a transcriptional activator or repressor depending on the
      developmental stage, the tissue or the target gene. Interestingly, since Cyclin G
      interacts with several CDKs, Cyclin G binding to the ETPs ASX or Corto suggests
      that their activity could depend on Cyclin G-mediated phosphorylation. We discuss
      whether Cyclin G fine-tunes transcription by controlling H2A ubiquitination and
      transcriptional elongation via interaction with the ASX subunit of PR-DUB.

PMID- 25995772
TI  - Efficacy of dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2
      diabetes undergoing hemodialysis.
AB  - BACKGROUND: Incretin therapy is feasible in patients with type 2 diabetes
      mellitus undergoing hemodialysis (HD). However, few studies have examined the
      safety and efficacy of this therapeutic approach in patients with diabetes and
      renal impairment. Here, we examined glycemic control and the anti-oxidative
      stress effects of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in
      patients with type 2 diabetes undergoing HD. METHODS: Thirty-five patients with
      type 2 diabetes undergoing HD (including 13 insulin-treated patients) were
      switched from ongoing therapy to linagliptin (5 mg, once daily). Levels of
      fasting blood glucose, C-peptide immunoreactivity (CPR), glycated albumin, B-type
      natriuretic peptide, oxidized low-density lipoprotein (oxLDL), high-sensitivity C
      reactive protein, 8-hydroxy-2'-deoxyguanosine (8OHdG), body mass index, blood
      pressure, and other biologic characteristics (liver function, renal function,
      lipid profile) were determined before and 3 months after linagliptin treatment.
      Patients were classified into insulin-treated and non-insulin groups. RESULTS:
      With the exception of levels of total bilirubin, aspartate aminotransferase, and
      CPR, none of the patients exhibited changes in glucose metabolism after switching
      to linagliptin treatment. However, oxLDL levels were decreased significantly by
      linagliptin therapy in the non-insulin-treated group despite the absence of
      changes in glycemic control. CONCLUSION: Linagliptin can decrease serum levels of
      oxLDL in patients with type 2 diabetes undergoing HD independent of its glucose
      lowering effect.

PMID- 25995773
TI  - Autocatalytic sets in E. coli metabolism.
AB  - BACKGROUND: A central unsolved problem in early evolution concerns self
      organization towards higher complexity in chemical reaction networks. In theory,
      autocatalytic sets have useful properties to help model such transitions.
      Autocatalytic sets are chemical reaction systems in which molecules belonging to
      the set catalyze the synthesis of other members of the set. Given an external
      supply of starting molecules - the food set - and the conditions that (i) all
      reactions are catalyzed by at least one molecule, and (ii) each molecule can be
      constructed from the food set by a sequence of reactions, the system becomes a
      reflexively autocatalytic food-generated network (RAF set). Autocatalytic
      networks and RAFs have been studied extensively as mathematical models for
      understanding the properties and parameters that influence self-organizational
      tendencies. However, despite their appeal, the relevance of RAFs for real
      biochemical networks that exist in nature has, so far, remained virtually
      unexplored. RESULTS: Here we investigate the best-studied metabolic network, that
      of Escherichia coli, for the existence of RAFs. We find that the largest RAF
      encompasses almost the entire E. coli cytosolic reaction network. We
      systematically study its structure by considering the impact of removing
      catalysts or reactions. We show that, without biological knowledge, finding the
      minimum food set that maintains a given RAF is NP-complete. We apply a randomized
      algorithm to find (approximately) smallest subsets of the food set that suffice
      to sustain the original RAF. CONCLUSIONS: The existence of RAF sets within a
      microbial metabolic network indicates that RAFs capture properties germane to
      biological organization at the level of single cells. Moreover, the
      interdependency between the different metabolic modules, especially concerning
      cofactor biosynthesis, points to the important role of spontaneous (non
      enzymatic) reactions in the context of early evolution. Graphical AbstractE. coli
      metabolic network in the context of autocatalytic sets.

PMID- 25995774
TI  - Framework for classifying compliance and medical immediacy among low-acuity
      presentations at an urban trauma center.
AB  - BACKGROUND: This research offers two exploratory frameworks, one for medical
      regimen compliance and one for medical immediacy. The first classifies compliance
      awareness, compliance mitigation, and financial limitation for those patients
      that exhibit nonadherence with a medical regimen. The second classifies medical
      immediacy and characterizes avoidable utilization. METHODS: Representative
      sampling of adult patients presenting at an emergency department (62,000/ppy)
      triaged as low acuity; emergency department physician assessment of noncompliance
      with medical regimen for those patients with a complaint related to a chronic
      condition; and emergency department physician assessment of medical immediacy and
      avoidable utilization. RESULTS: Physicians report 48.3% (95% confidence interval
      (CI) 43.5% to 53.1%) of patients with at least a single chronic condition are
      presenting with symptoms or complaint related to a chronic condition, and 39.6%
      (CI 31.7% to 47.4%) of these exhibit noncompliance with the medical regimen
      associated with that chronic condition. 16.4% (CI 6.6% to 26.1%) of the patients
      exhibit pseudo compliance, a belief that the medical regimen is in compliance
      when in fact it is not. If the patient had been in compliance, 85.9% (CI 77.0% to
      94.8%) of the presenting conditions may have been mitigated. Noncompliance cases
      (34.5% (CI 22.0% to 47.1%)) are partly attributable to financial constraints.
      Further, 19.1% (CI 15.7% to 22.5%) are assessed as requiring no medical
      intervention and 3.4% (CI 1.8% to 4.9%) require immediate stabilization.
      CONCLUSIONS: A large portion of low-acuity presentations are related to a chronic
      condition and noncompliance with the associated medical regimen contributes to
      the need to seek medical services. Interventions addressing literacy and
      financial constraints may increase compliance and decrease utilization.

PMID- 25995776
TI  - A case of squamous cell carcinoma of the skin due to the molecularly confirmed
      Lynch Syndrome.
AB  - Patients with Lynch Syndrome are at high risk for developing a variety of cancers
      including cancers of the colon or rectum, small bowel, stomach, uterus, renal
      pelvis, ureter, biliary tract, ovaries, brain and pancreas (N Engl J Med 348: 919
      32, 2003; Gut 57:1097-101, 2008; NCCN, Inc Guideline. Ft. Washington, PA. Online
      Version 2.2014). Lack of MLH-1 and MSH-2 expression commonly result from germline
      mutations in this inherited cancer syndrome. Here, we report the case of a
      patient with a molecularly confirmed germline mutation in MLH-1 along with a
      colon cancer showing lack of expression of MLH-1 as well as a squamous cell
      cancer of the skin from the abdominal wall also demonstrating lack of expression
      of MLH-1. This case appears to represent the second case report of a squamous
      cell skin cancer apparently due to the Lynch Syndrome and further supports a
      proposed relationship between Lynch Syndrome and these tumors. 

PMID- 25995775
TI  - Electroencephalographic and convulsive effects of binge doses of (+)
      methamphetamine, 5-methoxydiisopropyltryptamine, and (+/-)-3,4
      methylenedioxymethamphetamine in rats.
AB  - The abuse of drugs such as methamphetamine (MA), 3,4
      methylenedioxymethamphetamine (Ecstasy, MDMA), and 5-methoxydiisopropyltryptamine
      (5-MeO-DIPT; Foxy) is global. Symptoms from taking these drugs include
      tachycardia, agitation, hyperpyrexia, and sometimes seizures. We compared the EEG
      effects of these drugs in male Sprague-Dawley rats (~300 g) implanted with
      cortical electroencephalographic (EEG) electrodes prior to testing. Animals
      received four subcutaneous injections of MA, MDMA, or Foxy (10 mg/kg each as
      freebase, administered every 2 h), or saline as these doses produce lasting
      effects on learning, memory, and monoamines. EEG tracings were recorded before,
      during, and after treatment. Animals receiving MDMA showed no significant EEG
      abnormalities or myoclonus. MA treatment resulted in myoclonic activity and in
      brief (<10 s) EEG epileptiform activity in ~50% of the rats. Longer seizure
      activity (10 s to 5 min) was recorded in some MA-treated rats following the third
      and fourth doses. The onset of myoclonic activity following Foxy treatment
      occurred shortly after the first dose. All rats receiving Foxy showed seizures by
      the second dose and this continued throughout the treatment regimen. The results
      show that binge doses of MA and MDMA, which mimic the neurochemical changes seen
      in chronic users, increase EEG abnormalities after MA but not after MDMA. While
      the neurochemical effects of Foxy are not known in humans, this drug causes
      severe EEG abnormalities and overt seizures in 100% of tested animals.

PMID- 25995777
TI  - [Place of beating heart bypass surgery in kidney cancers with supradiaphragmatic
      invasion: about seven cases].

PMID- 25995778
TI  - Standardizing assessment practices of undergraduate medical competencies across
      medical schools: challenges, opportunities and lessons learned from a consortium
      of medical schools in Uganda.
AB  - INTRODUCTION: Health professions education is gradually moving away from the more
      traditional approaches to new innovative ways of training aimed at producing
      professionals with the necessary competencies to address the community health
      needs. In response to these emerging trends, Medical Education for Equitable
      Services to All Ugandans (MESAU), a consortium of Ugandan medical schools
      developed key competencies desirable of graduates and successfully implemented
      Competency Based Education (CBE) for undergraduate medical students. OBJECTIVES:
      To examine the current situation and establish whether assessment methods of the
      competencies are standardized across MESAU schools as well as establish the
      challenges, opportunities and lessons learned from the MESAU consortium. METHODS:
      It was a cross-sectional descriptive study involving faculty of the medical
      schools in Uganda. Data was collected using focus group discussions and document
      reviews. Findings were presented in form of themes. RESULTS: Although the MESAU
      schools have implemented the developed competencies within their curricular, the
      assessment methods are still not standardized with each institution having its
      own assessment procedures. Lack of knowledge and skills regarding assessment of
      the competencies was evident amongst the faculty. The fear for change amongst
      lecturers was also noted as a major challenge. However, the institutional
      collaboration created while developing competencies was identified as key
      strength. CONCLUSION: Findings demonstrated that despite having common
      competencies, there is no standardized assessment blue print applicable to all
      MESAU schools. Continued collaboration and faculty development in assessment is
      strongly recommended.

PMID- 25995779
TI  - Destructive invasion of the clavicle by desmoid tumor: a case report.
AB  - Desmoid tumors are rare, soft-tissue neoplasms that do not metastasize, but
      exhibit aggressive growth and local invasion. They originate most frequently from
      abdominal fascial structures, although they can also appear at extra-abdominal
      sites. The most common extra-abdominal locations include the shoulder, chest
      wall, back, thigh, and head and neck. In children, desmoid tumors are more
      infiltrative, having a tendency towards osseous involvement more frequently than
      in adult patients. We report acase of a supraspinatus muscle desmoid tumor in a
      female patient with clavicle destruction.

PMID- 25995780
TI  - A rare cause of generalized seizures: agenesis and Lipoma of the corpus Callosum.

PMID- 25995781
TI  - Factors for viral infection in blood donors of South Kivu in the Democratic
      Republic of Congo.
AB  - INTRODUCTION: Assessing the knowledge, attitudes, practices and behaviors among
      blood donors in South Kivu and identify risk factors for viral markers. METHODS:
      A descriptive and analytical cross-sectional study involved 595 blood donors in
      the city of Bukavu (Head city of the province of South Kivu) in the eastern
      Democratic Republic of Congo. RESULTS: Our sample consisted of 70.3% men with a
      median age of 23 and 77% of young people fewer than 30 years. The score of
      knowledge and attitude of blood donor's volunteer on blood safety were assessed
      at 23.5% and 79.1%. A statistically significant difference was observed between
      the loyal and new blood donors volunteer (25.1% vs 64.6% p < 0.001); between
      blood donors volunteer of low and high education level (p = 0.04). Motivation to
      donate blood in 95.9% of cases respect ethical rules of donation. The prevalence
      of viral markers in blood donors is as follows: 4.8% hepatitis B, 3.9% hepatitis
      C, 1.6% HIV. For HIV, the low level of education and replacement blood donors are
      most at risk, the antigen of hepatitis B is observed in blood donors over 30
      years, blood donors living couple. CONCLUSION: General knowledge on blood safety
      is very low in the first link in the chain transfusion (blood donors). A good
      education of this population conducted by the transfusion service reinforced
      building (training and support) is needed.

PMID- 25995782
TI  - Traumatic posterior sternoclavicular joint dislocation in a child: a case report.
AB  - Sternoclavicular joint dislocation is a rare event. It occurs most often in a
      violent trauma. The authors report the case of a10 years old child, received at
      emergencies for right shoulder blunt trauma after been punched by another child.
      He presented with right shoulder pain, right upper limb functional impairment and
      right sternoclavicular joint depression. Standard chest radiographs were normal.
      Chest CT scan showed posterior dislocation and allowed us to determine its
      variety. Twelve hours after the trauma, a closed reduction has been done under
      general anesthesia. A control CT scan showed a restoration of normal joint
      anatomy. After 18 months, the shoulder was painless and mobile in all directions.
      It is an isolated recent posterior sternoclavicular joint dislocation in a child.
      With this observation the authors emphasizeon the unusual mechanism of such a
      dislocation occurrence, the primary role of CT scan in the diagnosis and early
      closed reduction.

PMID- 25995783
TI  - [Superinfected pancreatitis revealed by psoas abscess].

PMID- 25995784
TI  - [Comparative and evolutionary profile of people infected with HIV on
      antiretroviral therapy in Kinshasa, Democratic Republic of Congo].

PMID- 25995785
TI  - [Obstetrical, infectious and traumatic factors associated with epilepsy in the
      rural area of Bangoua (West, Cameroon)].

PMID- 25995786
TI  - [Tetanus complicated with sepsis on major haemoglobinopathy].

PMID- 25995787
TI  - Dengue and hepatitis E virus infection in pregnant women in Eastern Sudan, a
      challenge for diagnosis in an endemic area.
AB  - Dengue fever and hepatitis E virus infection are both a public health problem in
      developing countries due to poor sanitation. Infection with viral hepatitis and
      dengue fever can present with similar clinical such and fever, headache and
      abortion. This study was conducted in Port-Sudan city in the eastern part of the
      country. ELISA and Real Time PCR tests were used to detect the infection. A total
      number of 39 pregnant women with a mean age 26 +/-7.8 were included in the study.
      All of them had fever, 32 (92.3%) admitted with headache, 11 (28.2%) of them had
      vomiting, and abortion was reported in two cases (5.1%). The study showed that 4
      (10.3%) of pregnant women were positive for the Hepatitis E virus, 5 (12.8%)
      positive for Dengue virus IgG, and only one sample (2.6%) was positive for IgM
      capture ELISA and real time PCR. Death due to hepatitis E infection was reported
      in one case with 7(th) month of pregnancy. Most of hepatitis cases were reported
      in the central sector of the Portsudan city. The diagnosis of hepatitis E virus
      and dengue virus in an endemic area is a great challenge for health care staff
      working in these areas. Both Dengue virus and Hepatitis E virus infection should
      be considered in pregnant women especially in similar settings.

PMID- 25995788
TI  - Evaluation of detection methods for Campylobacter infections among under-fives in
      Mwanza City, Tanzania.
AB  - INTRODUCTION: Campylobacter species are recognized as a major cause of acute
      gastroenteritis in humans throughout the world. The diagnosis is mainly based on
      stool culture. This study was done to evaluate the effectiveness of staining
      methods (Gram stain using 0.3% carbol fuchsin as counter stain and 1% carbol
      fuchsin direct stain) versus culture as the gold standard. METHODS: A total of
      300 children attending Bugando Medical Centre (BMC) and the Sekou Toure regional
      hospital with acute watery diarrhea were enrolled. Two sets of slides were
      prepared stained with 1% carbol fuchsin for 30 seconds first set, and the second
      set stained with Gram's stain using 0.3% carbol fuchsin as counter stain for five
      minutes. Concurrently, stool samples were inoculated on Preston Agar selective.
      RESULTS: Of 300 stool specimens, 14(4.7%) showed positive culture after 48 hours
      of incubation and 28 (9.3%) shows typical morphology of Campylobacter species by
      both Gram stain and direct stain. The sensitivity of the Gram stain using 0.3%
      carbol fuchsin as counter stain and 1% carbol fuchsin simple stain versus culture
      as gold standard was 64.3%, with a specificity of 93.4%. The positive predictive
      value and negative predictive value were 32.1% and 98.2% respectively.
      CONCLUSION: The detection of Campylobacter by 1% carbol fuchsin is simple,
      inexpensive, and fast, with both a high sensitivity and specificity. Laboratories
      in settings with high prevalence of campylobacteriosis and/or limited resources
      can employ 1% carbol fuchsin direct stain in detecting campylobacter infections.

PMID- 25995789
TI  - [Acute respiratory infection and nutritional status in children 0-5 years: case
      of university clinics of Lubumbashi, Democratic Republic of Congo].

PMID- 25995790
TI  - Benign breast lesions in Bayelsa State, Niger Delta Nigeria: a 5 year multicentre
      histopathological audit.
AB  - INTRODUCTION: There has been no previous study to classify benign breast lesions
      in details based on histopathologically confirmed diagnosis in Bayelsa State,
      Nigeria. This study therefore aims to review all cases of benign breast lesions
      seen in all the three centres in Bayelsa State with histopathology services over
      a five year period for a comprehensive baseline data in our community for
      management, research and education. METHODS: This is a multicentre retrospective
      descriptive study based on histopathological diagnosed benign breast lesions from
      January 2009 to December 2013. Archival results and slides on benign breast
      lesions were retrieved and analysed using simple statistical methods. RESULTS: A
      total of 228 benign breast lesions (68.3%) were seen among 334
      histopathologically diagnosed breast diseases. The male to female ratio was
      19.7:1. Peak age incidence was the third decade (43%) with a mean age of
      29.1years. Fibroadenoma was the most common benign breast disease (BBD)
      accounting for 45.6% of all the cases followed by fibrocystic change (23.1%). The
      mean ages of fibroadenoma and fibrocystic change were 23.1years and 31.1years
      respectively. Inflammatory breast lesions constituted 8.3%. We recorded only 2
      cases (0.9%) of atypical ductal hyperplasia (ADH) with no case of atypical
      lobular hyperplasia (ALH) within the study period. Gynaecomastia (4%) was the
      main male breast lesion in the study. CONCLUSION: Benign breast diseases are the
      most common breast lesions in Bayelsa State. Fibroadenoma is the most common
      lesion followed by fibrocystic change. The incidence of atypical hyperplasia
      recorded was rather low in the state.

PMID- 25995791
TI  - [Practice of prophylaxis for venous thromboembolic disease: survey of health
      professionals in Ouagadougou].

PMID- 25995792
TI  - Impact of pre-analytical factors on mycobacterium cultures contaminations rates
      in Burkina Faso, West Africa.
AB  - INTRODUCTION: For a high quality level diagnosis, mycobacterium culture must
      comply with the pre-analytical and analytical conditions recommended by the WHO
      and the country National Tuberculosis Program (NTP). In this study, we determined
      whether temperature and duration of sputum storage were associated with culture
      contamination in Burkina Faso. METHODS: Sputa were collected in 5 districts labs
      in Burkina Faso. Temperature and duration of sputum storage were recorded. After
      the collection, sputa were decontaminated using Petroff modified method, and the
      pellet was inoculated on LJ media and LJ media supply with 2% sodium pyruvate.
      Risk of culture contamination associated with temperature and duration of sputum
      storage was measured by Chi2 test and logistic regression. RESULTS: Out of 404
      specimens, 61% (246/404) were stored between 2 and 8 degrees C, and 15% (61/404)
      were processed within three days. The global contamination rate was 24%, with
      only 8% for samples respecting WHO recommendations, up to 35% for others. Storage
      at room temperature was associated with a significantly higher risk of
      contamination compared to storage at 2-8 degrees C (OR 2.24, p = 0.001, IC 95%).
      CONCLUSION: The recommendations about the temperature and the duration of sputum
      storage before cultures are not completely respected. This leads to high
      contamination rate of mycobacterium culture. It will be necessary to take
      logistics measures in peripherals health services or to develop more selective
      medium for mycobacterium culture in low income countries.

PMID- 25995793
TI  - [Traumatic dislocation of the hip in children (about one case)].

PMID- 25995794
TI  - A surveillance of nosocomial candida infections: epidemiology and influences on
      mortalty in intensive care units.
AB  - INTRODUCTION: It was aimed to investigate the frequency of Candida infections
      (CI) in the intensive care units (ICU), to determine typing of candida to
      evaluate risk factors associated with CI and mortality, and to evaluate influence
      of CI on mortality. METHODS: The prospective cohort study was carried out between
      Jan 1, 2009 and Dec 31, 2010 in ICUs, and the patients were observed with active
      surveillance. VITEK 2 Compact System (BioMerieux, France) kits were used for the
      identification of isolates from various clinical samples. RESULTS: A total of
      2362 patients had enrolled for 16135 patients-days into the study. During the
      study, 63 (27,5%) of patients developed 77 episodes of CI were observed. Of the
      patients; 54% were male, 46% were female. Duration of hospitalization (OR = 1,03,
      p = 0,007), hyperglycemia (OR = 17,93, p = 0,009), and co-infections (OR = 3,98,
      p = 0,001) were identified as independent risk factors for CI. The most common
      infections were bloodstream (53%). 77 of 135 candida strains was isolated as
      causative pathogens. C. albicans (63,6%) was the most frequent species. Overall
      mortality rate was 78%. The rates of mortality attributable to CI and candidemia
      were 27%, and 18,3% respectively. Species- specific mortality rates of C.albicans
      and C.tropicalis were determined as 12%. High APACHE II scores (OR = 1,37; p =
      0,002), and the use of central venous catheter (OR = 9,01; p = 0,049) were
      assigned as independent risk factors for mortality. CONCLUSION: CI is an
      important problem in our hospital. CI and associated mortality can be prevented
      by controlling of risk factors. Updating of epidemiological data is required for
      successful antifungal treatment.

PMID- 25995795
TI  - [Sudden hearing loss: a retrospective study about 36 cases].

PMID- 25995796
TI  - Simultaneous double dislocation of the interphalangeal joint of the same finger:
      a report of two cases.
AB  - Simultaneous dislocation of both the proximal and distal interphalangeal (PIP and
      DIP) joints in a finger is uncommon. Two patients were treated conservatively.
      Both two patients fell from a step-ladder and X-rays revealed dorsal dislocations
      of both PIP and DIP joints of their right little fingers. Manual reduction was
      easily achieved with gentle longitudinal traction. The mechanism of the injury is
      believed to be hyperextension of both the DIP and PIP joints. Closed reduction is
      the treatment of choice and early active range of motion to prevent joint
      contracture should be recommended. 

PMID- 25995797
TI  - Intracavitary hydatid cyst of the left ventricle in child: an emergency surgery
      case report.
AB  - Hydatid cysts of the heart are very rare in child. In this report we describe an
      interesting and unique case of an 8-year-old boy with a large cardiac
      intracavitary hydatid cyst filling the left ventricle. Echocardiography,
      computerized tomography, magnetic resonance imaging and serologic test were
      necessary for the diagnosis. Once assessing the diagnosis, an emergency open
      heart surgery was necessary to prevent the complications. Surgery associated to
      medical treatment provides good results as demonstrated in this case report. 

PMID- 25995798
TI  - Hemiparesis post cerebral malaria.
AB  - Cerebral malaria is one of the most serious complications in the Plasmodium
      falciparum infection. In endemic areas, the cerebral malaria interested mainly
      children. The occurrence in adults is very rare and most interested adult
      traveling in tropical zones. This case report describes a motor deficit post
      cerebral malaria in a young adult traveling in malaria endemic area. This
      complication has been reported especially in children and seems very rare in
      adults. 

PMID- 25995799
TI  - [About a rare case of atypical rhabdoid teratoid tumor of the central nervous
      system in a pregnant woman].

PMID- 25995800
TI  - Cutis Laxa syndrome: a case report.
AB  - Cutis laxa (CL) is a heterogeneous group of inherited and acquired connective
      tissue disorders characterized by a loose skin and variable systemic involvement
      (inguinal hernia, cardiopulmonary disease, and emphysema). Autosomal dominant,
      autosomal recessive and x-linked recessive patterns have been described in the
      inherited forms. Acquired forms of this disease have been associated with a
      previous inflammatory skin disorder (urticaria...). The characteristic
      symptomatological pattern is resulting from paucity of elastic fibers. We report
      an 18 months old baby boy with a congenital cutis laxa. He was admitted in
      pediatric unit for respiratory disorders. The diagnosis of CL syndrome is based
      on clinical assessment of typical skin features and the associated extracutaneous
      finding. 

PMID- 25995801
TI  - [Primitive epiploic appendagitis : about five cases].

PMID- 25995802
TI  - [Meningoencephalitis by Streptococcus agalactiae in the immunocompetent adult].

PMID- 25995803
TI  - [Muco-epidermoid carcinoma in a young girl of 21 years].

PMID- 25995804
TI  - [Bacterial meningo-vasculitis revealing a pituitary adenoma].

PMID- 25995805
TI  - [Primitive Sjogren syndrome in the elderly: clinical and immunological
      characteristics].

PMID- 25995806
TI  - [Retinal vein occlusion and hyper-viscosity syndrome].

PMID- 25995807
TI  - Factors influencing the uptake of family planning services in the Talensi
      District, Ghana.
AB  - INTRODUCTION: Usage of family planning services in developing countries have been
      found to avert unintended pregnancies, reduce maternal and child mortality,
      however, it's usage still remains low. Hence, the objective of this study was to
      investigate the factors that influence the decision of women in fertility age to
      go for family planning services. METHODS: This was a descriptive cross-sectional
      study conducted in Talensi district in the Upper East Region of Ghana. Systematic
      random sampling was used to recruit 280 residents aged 15-49 years and data was
      analysed using SPSS version 21.0. RESULTS: The study revealed that 89% (249/280),
      of respondents were aware of family planning services, 18% (50/280) of
      respondents had used family planning services in the past. Parity and educational
      level of respondents were positively associated with usage of family planning
      services (P<0.05). Major motivating factors to the usage of family planning
      service were to space children, 94% (47/50) and to prevent pregnancy and sexual
      transmitted infections 84% (42/50). Major reasons for not accessing family
      planning services were opposition from husbands, 90% (207/230) and misconceptions
      about family planning, 83% (191/230). CONCLUSION: Although most women were aware
      of family planning services in the Talensi district, the uptake of the service
      was low. Thus, there is the need for the office of the district health
      directorate to intensify health education on the benefits of family planning with
      male involvement. The government should also scale up family planning services in
      the district to make it more accessible.

PMID- 25995808
TI  - [Paraplegia complicating anterior abdominal stab wound].

PMID- 25995809
TI  - [Humeral localization of a recurrent giant cell tumor (about one case)].

PMID- 25995810
TI  - Bilateral stellate neuroretinitis revealing a pheochromocytoma.
AB  - Neuroretinitis (NR) is an inflammatory disorder characterized by optic disc edema
      and subsequent formation of a macular star. We present a case of a 33 year old
      woman patient admitted for a progressive bilateral visual loss since two weeks.
      Fundus examination showed bilateral stellate neuroretinitis. Physical examination
      revealed a malignant hypertension of 210/150 mmHg. Magnetic resonance imaging
      identified a left suprarenal mass, whereas urinary catecholamine level was
      abnormally high which supported a diagnosis of pheochromocytoma. The patient
      underwent a laparoscopic left suprarenal adrenalectomy after successful control
      of blood pressure. histopathologic examination confirmed the diagnosis of
      pheochromocytoma. Visual acuity was restored and the retinal alterations
      disappeared 7 months after surgery.

PMID- 25995811
TI  - [Late discovery of type III osteogenesis imperfecta: about a case].

PMID- 25995812
TI  - Secondary peritoneal hydatidosis, the challenges of echinococcal disease in South
      Sudan: a case report.
AB  - A 28 year old male presented to the Juba Teaching Hospital with progressive
      shortness of breath. 18 months prior to admission, he presented to a rural
      hospital with severe abdominal pain. An emergency laparotomy was performed, and a
      large hepatic cyst was removed. Examination at the Juba Teaching hospital
      revealed a grossly distended abdomen with multiple palpable masses per abdomen.
      An Abdominal Ultrasound revealed multiple loculated cysts throughout the abdomen.
      A diagnosis of Secondary Peritoneal Hydatidosis resulting from incorrectly
      performed surgery was made. The patient was conservatively treated and at 14
      weeks, the cysts showed a moderate reduction in size. Cystic Echinococcus (CE) is
      common in South Sudan and has a considerable disease burden throughout the
      developing world. Greater governmental and international support is required to
      develop effective control measures for these diseases.

PMID- 25995813
TI  - [Post-traumatic diaphragmatic hernia].

PMID- 25995814
TI  - Atypical eclampsia and postpartum status epilepticus.
AB  - Preeclampsia is an entity that may present from 20th week of gestation up to 48
      hours postpartum and is associated with hypertension and proteinuria. Eclampsia
      is emergence of convulsions pre-eclampsia in pregnant women with signs and
      symptoms. Recent studies showed that in some women, preeclampsia and even
      eclampsia may occur without hypertension or proteinuria. Here, we present a case
      of 26 years old women who had an uneventful pregnancy until 30 weeks' of
      gestation. She had only proteinuria in laboratory tests and was diagnosed as
      status epilepticus in early postpartum period. Preeclampsia and eclampsia is
      related with serious fetal and maternal morbidity and mortality and may present
      with atypical course. The awareness of atypical cases of preeclampsia enhances
      early diagnosis and management which are critical to avoid feto-maternal
      complications. 

PMID- 25995815
TI  - Gaucher's disease: report of 11 cases with review of literature.
AB  - Gaucher's disease (GD) is a lysosomal storage disorder due to glucocerebrosidase
      deficiency; it's one of the rare genetic diseases for which therapy is now
      available. The purpose of this work is to study the epidemiological features of
      the disease and to highlight the diagnostic difficulties. We performed an 11-year
      retrospective study of 11 patients with GD followed-up in the department of
      paediatric hepatology gastroenterology and nutrition of Rabat children's
      Hospital. We observed 11 patients with GD: 6 males and 5 females. Age at onset
      ranged from 3 months to 10 years with an average of 3.41 years. Mean age at
      diagnosis was 4 years (range 3 months-14 years). Parental consanguinity was noted
      in 85% cases. According to the clinical presentation, we classified our patients
      into: 9 cases of type 1 (81%) and two cases of type 2 (19%), none of the patients
      presented GD type 3. GD type 1: The age at diagnosis ranged from 2 years to 14
      year with an average of 6 years. Main symptoms were: splenomegaly, hepatomegaly,
      pallor, haemorrhagic appearance (40%), bone pain (40%). The diagnosis was based
      on histology showing the Gaucher's cells in various tissues (100%). Enzymatic
      activity dosage confirmed the diagnosis of GD for 4 patients (44.5%). The
      treatment was always symptomatic (analgesics, transfusion). A splenectomy was
      performed in one case presenting with multiple splenic abscesses and high
      transfusion requirements. None of the patients received a specific treatment
      (substitutive enzymotherapy). The follow-up period ranged from 3 months to 6
      years with an average follow-up of 4 years. We noticed stability in 4 cases, 2
      worsening cases with bone and spleen complications. Three patients were lost to
      follow-up. GD type 2: we observed two cases of GD type 2 diagnosed at 3 and 18
      months. The visceral symptoms were serious and the neurological features included
      seizures, hypertony, squint, physical developmental milestones delay. Both of
      them died. Gaucher's disease is not exceptional in Morocco. Type 1 is the most
      common type. We noted through this study some diagnostic difficulties as the
      diagnosis was delayed and the enzymatic dosage was performed in only 42% of the
      cases as well as therapeutic difficulty with no prescription of the specific
      treatment given the high cost of the enzyme.

PMID- 25995816
TI  - Cutaneous metastasis reveling lung cancer.

PMID- 25995817
TI  - Prevention of mother-to-child transmission of the Human Immunodeficiency Virus:
      investigating the uptake and utilization of maternal and child health services in
      Tiko health district, Cameroon.
AB  - INTRODUCTION: Despite evidence that interventions to prevent mother-to-child
      transmission (PMTCT) of HIV are effective in ensuring a healthy child and keeping
      mothers alive, there are many challenges to achieving successful interventions in
      Cameroon. The study was conducted to investigate factors that affect access to
      and utilization of maternal and child health (MCH) and PMTCT services among women
      in Tiko health district in Cameroon. METHODS: We conducted a cross-sectional,
      descriptive study on women of reproductive age who had experienced a pregnancy
      using a self-administered, structured questionnaire, in health facilities
      offering PMTCT services and in communities within the district. RESULTS: Four
      hundred and thirteen women were interviewed. The majority, 98.4%, of them
      attended antenatal care (ANC) during their most recent pregnancy. Of these women,
      87.4% of them made at least four ANC visits. HIV testing during the first visit
      among the ANC attendees was 85.5%. Approximately, 92.1% of women who tested for
      HIV received their results on the same day. All participants reported to have
      given birth in a health facility during their most recent pregnancy. No education
      (Odds Ratio [OR] 0.11; 95% CI 0.01-0.83) and acquisition of primary education (OR
      0.25; 95% CI 0.06-0.88) was associated with better male partner involvement in
      PMTCT. CONCLUSION: The uptake of MCH/PMTCT services was high in this study.
      Further exploration of these levels is warranted so that this model of care and
      engagement can be replicated in other parts of the country where uptake is low.

PMID- 25995819
TI  - A cannabinoid receptor agonist N-arachidonoyl dopamine inhibits adipocyte
      differentiation in human mesenchymal stem cells.
AB  - Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB)
      receptors, transient receptor potential cation channel, subfamily V, member 1
      (TRPV1) and peroxisome proliferator-activated receptor gamma (PPARgamma). The
      stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene
      transcription of the CB1 receptor, TRPV1 and PPARgamma. In this study, the
      effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N
      arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis
      in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA
      whereas inhibited by NADA. No change was observed by the treatment of non
      cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the
      regulation of adipogenesis is associated with their effects on PPARgamma
      transactivation. AEA can directly activate PPARgamma. The effect of AEA on
      PPARgamma in hBM-MSCs may prevail over that on the CB1 receptor mediated signal
      transduction, giving rise to the AEA-induced promotion of adipogenesis. In
      contrast, NADA had no effect on the PPARgamma activity in the PPARgamma
      transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs
      was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a CB1
      antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM
      MSCs, which may be interpreted as the result of the inverse agonism of the CB1
      receptor. This result suggests that the constantly active CB1 receptor may
      contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the
      selective CB1 agonists that are unable to affect cellular PPARgamma activity
      inhibit adipogenesis in hBM-MSCs. 

PMID- 25995820
TI  - Antitumor Effects of Fucoidan on Human Colon Cancer Cells via Activation of Akt
      Signaling.
AB  - We identified a novel Akt signaling mechanism that mediates fucoidan-induced
      suppression of human colon cancer cell (HT29) proliferation and anticancer
      effects. Fucoidan treatment significantly inhibited growth, induced G1-phase
      associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin
      dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan
      treatment activated the Akt signaling pathway, which was inhibited by treatment
      with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan
      induced decrease in cell proliferation, the induction of G1-phase-associated
      p21WAF1 expression, and the reduction in cell cycle regulatory protein
      expression. Intraperitoneal injection of fucoidan reduced tumor volume; this
      enhanced antitumor efficacy was associated with induction of apoptosis and
      decreased angiogenesis. These data suggest that the activation of Akt signaling
      is involved in the growth inhibition of colon cancer cells treated with fucoidan.
      Thus, fucoidan may serve as a potential therapeutic agent for colon cancer. 

PMID- 25995818
TI  - Role of micronutrients in skin health and function.
AB  - Skin is the first line of defense for protecting our bodies against external
      perturbations, including ultraviolet (UV) irradiation, mechanical/chemical
      stress, and bacterial infection. Nutrition is one of many factors required for
      the maintenance of overall skin health. An impaired nutritional status alters the
      structural integrity and biological function of skin, resulting in an abnormal
      skin barrier. In particular, the importance of micronutrients (such as certain
      vitamins and minerals) for skin health has been highlighted in cell culture,
      animal, and clinical studies. These micronutrients are employed not only as
      active compounds in therapeutic agents for treating certain skin diseases, but
      also as ingredients in cosmetic products. Here, the author describes the barrier
      function of the skin and the general nutritional requirements for skin health.
      The goal of this review is to discuss the potential roles and current knowledge
      of selected micronutrients in skin health and function. 

PMID- 25995821
TI  - The inhibitory effect of shikonin on the agonist-induced regulation of vascular
      contractility.
AB  - Shikonin, a natural flavonoid found in the roots of Lithospermum erythrorhizon,
      has been shown to possess many biological functions. The present study was
      undertaken to investigate the influence of shikonin on vascular smooth muscle
      contractility and to determine the mechanism involved. Denuded aortic rings from
      male rats were used and isometric contractions were recorded and combined with
      molecular experiments. Shikonin significantly relaxed fluoride-, thromboxane A2-
      or phorbol ester-induced vascular contraction suggesting as a possible anti
      hypertensive on the agonist-induced vascular contraction regardless of
      endothelial nitric oxide synthesis. Furthermore, shikonin significantly inhibited
      fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases
      in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase
      activity and the subsequent phosphorylation of MYPT1 and the inhibition of MEK
      activity and the subsequent phosphorylation of ERK1/2. This study provides
      evidence regarding the mechanism underlying the relaxation effect of shikonin on
      agonist-induced vascular contraction regardless of endothelial function. 

PMID- 25995823
TI  - Protective effects of silibinin and its possible mechanism of action in mice
      exposed to chronic unpredictable mild stress.
AB  - Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk
      thistle herb, has recently been identified as having anti-hepatotoxic and
      anticancer properties. In this paper, we investigated the effects of silibinin on
      behavior and neuroplasticity in mice subjected to chronic unpredictable mild
      stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with
      silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive
      weeks. The results showed that silibinin administration significantly alleviated
      the CUMS-induced depressive-like behavior, including the total number of squares
      crossed and the frequency of rearing in the open field test, the immobility time
      in the tail suspension test and the forced swimming test. Furthermore, silibinin
      treatment increased the levels of brain-derived neurotrophic factor (BDNF),
      serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and
      hippocampus. Our study provides new insight into the protective effects of
      silibinin on the depressive status of CUMS mice, specifically by improving
      neuroplasticity and neurotransmission. 

PMID- 25995825
TI  - Effect of pioglitazone on excitotoxic neuronal damage in the mouse hippocampus.
AB  - Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma
      agonist, is known to regulate inflammatory process and to have neuroprotective
      effects against neurological disorders. In the present study, we examined the
      effects of 30 mg/kg PGZ on excitotoxic neuronal damage and glial activation in
      the mouse hippocampus following intracerebroventricular injection of kainic acid
      (KA). PGZ treatment significantly reduced seizure-like behavior. PGZ had the
      neuroprotective effect against KA-induced neuronal damage and attenuated the
      activations of astrocytes and microglia in the hippocampal CA3 region. In
      addition, MPO and NFkappaB immunoreactivities in the glial cells were also
      decreased in the PGZ-treated group. These results indicate that PGZ had
      anticonvulsant and neuroprotective effects against KA-induced excitotocix injury,
      and that neuroprotective effect of PGZ might be due to the attenuation of KA
      induced activation in astrocytes and microglia as well as KA-induced increases in
      MPO and NFkappaB. 

PMID- 25995824
TI  - Repeated neonatal propofol administration induces sex-dependent long-term
      impairments on spatial and recognition memory in rats.
AB  - Propofol is an anesthetic agent that gained wide use because of its fast
      induction of anesthesia and rapid recovery post-anesthesia. However, previous
      studies have reported immediate neurodegeneration and long-term impairment in
      spatial learning and memory from repeated neonatal propofol administration in
      animals. Yet, none of those studies has explored the sex-specific long-term
      physical changes and behavioral alterations such as social (sociability and
      social preference), emotional (anxiety), and other cognitive functions (spatial
      working, recognition, and avoidance memory) after neonatal propofol treatment.
      Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal
      injections of propofol or normal saline for 7 days. Starting fourth week of age
      and onwards, rats were subjected to behavior tests including open-field, elevated
      plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition,
      passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal
      protein expressions were analyzed by Western blot. Results revealed long-term
      body weight gain alterations in the growing rats and sex-specific impairments in
      spatial (female) and recognition (male) learning and memory paradigms. A markedly
      decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and
      increased expression of AMPA GluR1 subunit protein expression in male rats were
      also found. Other aspects of behaviors such as locomotor activity and
      coordination, anxiety, sociability, social preference and avoidance learning and
      memory were not generally affected. These results suggest that neonatal repeated
      propofol administration disrupts normal growth and some aspects of
      neurodevelopment in rats in a sex-specific manner. 

PMID- 25995822
TI  - Dieckol, a Component of Ecklonia cava, Suppresses the Production of MDC/CCL22 via
      Down-Regulating STAT1 Pathway in Interferon-gamma Stimulated HaCaT Human
      Keratinocytes.
AB  - Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the
      inflammatory chemokines that controls the movement of monocytes, monocyte-derived
      dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are
      elevated in atopic dermatitis, which suggests that the chemokines produced from
      keratinocytes are responsible for attracting inflammatory lymphocytes to the
      skin. A major signaling pathway in the interferon-gamma (IFN-gamma)-stimulated
      inflammation response involves the signal transducers and activators of
      transcription 1 (STAT1). In the present study, we investigated the anti
      inflammatory effect of dieckol and its possible action mechanisms in the category
      of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22
      production induced by IFN-gamma (10 ng/mL) in a dose dependent manner. Dieckol (5
      and 10 MUM) suppressed the phosphorylation and the nuclear translocation of
      STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via
      the down-regulation of STAT1 activation. 

PMID- 25995827
TI  - Neuroprotective and antioxidant effects of novel benzofuran-2-carboxamide
      derivatives.
AB  - In the present study, we synthesized a series of novel 7-methoxy-N-(substituted
      phenyl)benzofuran-2-carboxamide derivatives in moderate to good yields and
      evaluated their neuroprotective and antioxidant activities using primary cultured
      rat cortical neuronal cells and in vitro cell-free bioassays. Based on our
      primary screening data with eighteen synthesized derivatives, nine compounds (1a,
      1c, 1f, 1i, 1j, 1l, 1p, 1q and 1r) exhibiting considerable protection against the
      NMDA-induced excitotoxic neuronal cell damage at the concentration of 100 MUM
      were selected for further evaluation. Among the selected derivatives, compound 1f
      (with -CH3 substitution at R2 position) exhibited the most potent and efficacious
      neuroprotective action against the NMDA-induced excitotoxicity. Its
      neuroprotective effect was almost comparable to that of memantine, a well-known
      NMDA antagonist, at 30 MUM concentration. In addition to 1f, compound 1j (with 
      OH substitution at R3 position) also showed marked anti-excitotoxic effects at
      both 100 and 300 MUM concentrations. These findings suggest that -CH3
      substitution at R2 position and, to a lesser degree, -OH substitution at R3
      position may be important for exhibiting neuroprotective action against
      excitotoxic damage. Compound 1j was also found to scavenge 1,1-diphenyl-2
      picrylhydrazyl radicals and inhibit in vitro lipid peroxidation in rat brain
      homogenate in moderate and appreciable degrees. Taken together, our structure
      activity relationship studies suggest that the compound with -CH3 substitution at
      R2 and -OH substitution at R3 positions of the benzofuran moiety might serve as
      the lead exhibiting potent anti-excitotoxic, ROS scavenging, and antioxidant
      activities. Further synthesis and evaluation will be necessary to confirm this
      possibility. 

PMID- 25995826
TI  - Treatment of GABA from Fermented Rice Germ Ameliorates Caffeine-Induced Sleep
      Disturbance in Mice.
AB  - gamma-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the
      mammalian central nervous system, is involved in sleep physiology. Caffeine is
      widely used psychoactive substance known to induce wakefulness and insomnia to
      its consumers. This study was performed to examine whether GABA extracts from
      fermented rice germ ameliorates caffeine-induced sleep disturbance in mice,
      without affecting spontaneous locomotor activity and motor coordination. Indeed,
      caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice.
      Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg,
      p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by
      caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not
      significantly reduced the caffeine-induced increase in locomotor activity without
      affecting motor coordination. Additionally, rice germ ferment extracts-GABA per
      se did not affect the spontaneous locomotor activity and motor coordination of
      mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter
      the sleep disturbance induced by caffeine, without affecting the general
      locomotor activities of mice. 

PMID- 25995828
TI  - Phenolic Compounds from the Leaves of Stewartia pseudocamellia Maxim. and their
      Whitening Activities.
AB  - The half-dried leaves of Stewartia. pseudocamellia were extracted with hot water
      (SPE) and partitioned with n-hexane (SPEH), dichloromethane (SPED), and ethyl
      acetate (SPEE) successively. SPE and SPEE showed significant inhibitory effects
      against melanogenesis and tyrosinase activities. By bioassay-guided isolation,
      ten phenolic compounds were isolated by column chromatography from SPEE. The
      whitening effect of the isolated compounds from SPEE were tested for the
      inhibitory activities against melanogenesis using B16 melanoma cells, in vitro
      inhibition of tyrosinase, and L-3,4-dihydorxy-indole-2-carboxylic acid (L-DOPA)
      auto-oxidation assay. A cytotoxic activity assay was done to examine the cellular
      toxicity in Raw 264.7 macrophage cells. Of the compounds isolated, gallic acid
      and quercetin revealed significant inhibitory activities against melanogenesis
      compared to arbutin. In particular, quercetin exhibited similar inhibitory
      activities against tyrosinase and L-DOPA oxidation without cytotoxicity. These
      results suggested that SPE could be used as a potential source of natural skin
      whitening material in cosmetics as well as in food products. 

PMID- 25995829
TI  - Defensive Behavior against Noxious Heat Stimuli Is Declined with Aging Due to
      Decreased Pain-Associated Gene Expression in Drosophila.
AB  - Aging is defined as a collective process that alters organism's functional
      capacity and appearance over the course of life. Apart from an increase in
      susceptibility to many diseases, aging affects the cellular system that is
      responsible for decoding painful stimuli. Yet, aging-associated molecular
      mechanisms of pain perception remains elusive. Using Drosophila, we showed a
      decrease in temperature tolerance and a reduction in high temperature thermal
      avoidance with aging. Locomotor activity assay demonstrated that the age
      dependent changes in heat nociception did not stem from the general decline in
      muscular activity. However, we identified pain-related gene expression alteration
      with aging. We anticipate that our findings would help opening a new window onto
      developing the optimal pain treatment for the elderly. 

PMID- 25995830
TI  - Preclinical Pharmacokinetic Evaluation of beta-Lapachone: Characteristics of Oral
      Bioavailability and First-Pass Metabolism in Rats.
AB  - beta-Lapachone has drawn increasing attention as an anti-inflammatory and anti
      cancer drug. However, its oral bioavailability has not been yet assessed, which
      might be useful to develop efficient dosage forms possibly required for non
      clinical and clinical studies and future market. The aim of the present study was
      thus to investigate pharmacokinetic properties of beta-lapachone as well as its
      first-pass metabolism in the liver, and small and large intestines after oral
      administration to measure the absolute bioavailability in rats. A sensitive HPLC
      method was developed to evaluate levels of beta-lapachone in plasma and organ
      homogenates. The drug degradation profiles were examined in plasma to assess the
      stability of the drug and in liver and intestinal homogenates to evaluate first
      pass metabolism. Pharmacokinetic profiles were obtained after oral and
      intravenous administration of beta-lapachone at doses of 40 mg/kg and 1.5 mg/kg,
      respectively. The measured oral bioavailability of beta-lapachone was 15.5%. The
      considerable degradation of beta-lapachone was seen in the organ homogenates but
      the drug was quite stable in plasma. In conclusion, we suggest that the fairly
      low oral bioavailability of beta-lapachone may be resulted from the first-pass
      metabolic degradation of beta-lapachone in the liver, small and large intestinal
      tracts and its low aqueous solubility. 

PMID- 25995831
TI  - Association between the TCF7L2 rs12255372 (G/T) gene polymorphism and type 2
      diabetes mellitus in a Cameroonian population: a pilot study.
AB  - BACKGROUND: To study the relationship between the rs12255372 (G/T) polymorphism
      of the transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM)
      in a Cameroonian population. METHODS: This case-control study included 60 T2DM
      patients and 60 healthy normoglycemic controls, all unrelated and of Cameroonian
      origin, aged above 40 years (range 40-87). The Restriction Fragment Length
      Polymorphism - Polymerase Chain Reaction (RFLP-PCR) was used for genotyping.
      RESULTS: The T allele frequency was significantly higher in the diabetic group
      (0.44) than in the control group (0.17). This allele was significantly associated
      to a greater risk of developing T2DM as compared to the G allele (OR = 3.92, 95%
      CI 2.04 - 7.67, p < 0.0001). The codominant (additive) model explained best the
      risk of developing the disease, as the TT genotype was significantly associated
      to T2DM when compared to the GG genotype (OR = 4.45, 95% CI 1.64 - 12.83, p =
      0.0014). By logistic regression adjusted for age, this OR was 4.33 (95% CI: 1.57 
      11.92, p = 0.005). CONCLUSION: Our findings suggest that the rs12255372 (G/T)
      polymorphism of the TCF7L2 gene is an important risk factor for T2DM in the
      Cameroonian population.

PMID- 25995832
TI  - The diagnosis of right heart thrombus by focused cardiac ultrasound in a
      critically ill patient in compensated shock.
AB  - Right heart thrombus (RHT) is a life-threatening diagnosis that is rarely made in
      the emergency department (ED), but with the increasing use of focused cardiac
      ultrasound (FocUS), more of these cases may be identified in a timely fashion. We
      present a case of an ill-appearing patient who had an immediate change in
      management due to the visualization of RHT soon after arrival to the ED. The
      diagnosis was confirmed after a cardiology-performed ultrasound (US). This case
      illustrates the value of the recognition of RHT on FocUS and how US protocols
      designed for the evaluation of shock and shortness of breath may potentially be
      expanded to patients in a 'compensated' or 'pre-shock' state to expedite the
      correct diagnosis and to facilitate more timely management. 

PMID- 25187878
TI  - Density but not climate affects the population growth rate of guanacos ( Lama
      guanicoe) (Artiodactyla, Camelidae).
AB  - We analyzed the effects of population density and climatic variables on the rate
      of population growth in the guanaco ( Lama guanicoe), a wild camelid species in
      South America. We used a time series of 36 years (1977-2012) of population
      sampling in Tierra del Fuego, Chile. Individuals were grouped in three age
      classes: newborns, juveniles, and adults; for each year a female population
      transition matrix was constructed, and the population growth rate (lambda) was
      estimated for each year as the matrix highest positive eigenvalue. We applied a
      regression analysis with finite population growth rate (lambda) as dependent
      variable, and total guanaco population, sheep population, annual mean
      precipitation, and winter mean temperature as independent variables, with and
      without time lags. The effect of guanaco population size was statistically
      significant, but the effects of the sheep population and the climatic variables
      on guanaco population growth rate were not statistically significant. 

PMID- 25995833
TI  - Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene
      expression and stress response in healthy Caucasian males.
AB  - BACKGROUND: Previous research reported that individual differences in the stress
      response were moderated by an interaction between individuals' life stress
      experience and the serotonin transporter-linked polymorphic region (5-HTTLPR), a
      common polymorphism located in the promoter region of the serotonin transporter
      gene (SLC6A4). Furthermore, this work suggested that individual differences in
      SLC6A4 DNA methylation could be one underlying mechanism by which stressful life
      events might regulate gene expression. The aim of this study was to understand
      the relation between early and recent life stress experiences, 5-HTTLPR genotype,
      and SLC6A4 methylation. In addition, we aimed to address how these factors
      influence gene expression and cortisol response to an acute psychosocial
      stressor, operationalized as the Trier Social Stress Test (TSST). In a sample of
      105 Caucasian males, we collected early and recent life stress measures and blood
      samples to determine 5-HTTLPR genotype and SLC6A4 methylation. Furthermore, 71 of
      these participants provided blood and saliva samples before and after the TSST to
      measure changes in SLC6A4 and NR3C1 gene expression and cortisol response.
      RESULTS: Compared to S-group individuals, LL individuals responded with increased
      SLC6A4 mRNA levels to the TSST (t(66) = 3.71, P < .001) and also showed increased
      global methylation as a function of ELS (r (32) = .45, P = .008) and chronic
      stress (r (32) = .44, P = .010). Compared to LL individuals, S-group individuals
      showed reduced SLC6A4 mRNA levels (r (41) = -.31, P = .042) and increased F3
      methylation (r (67) = .30, P = .015) as a function of ELS; as well as increased
      F1 methylation as a function of chronic stress and recent depressive symptoms (r
      = .41, P < .01), which correlated positively with NR3C1 expression (r (42) = .31,
      P = .040). CONCLUSIONS: Both early and recent life stress alter DNA methylation
      as a function of 5-HTTLPR genotype. Some of these changes are also reflected in
      gene expression and cortisol response, differentially affecting individuals'
      stress response in a manner that may confer susceptibility or resilience for
      psychopathology upon experiencing stressful life events.

PMID- 25995835
TI  - Numerical calculation of protein-ligand binding rates through solution of the
      Smoluchowski equation using smoothed particle hydrodynamics.
AB  - BACKGROUND: The calculation of diffusion-controlled ligand binding rates is
      important for understanding enzyme mechanisms as well as designing enzyme
      inhibitors. METHODS: We demonstrate the accuracy and effectiveness of a
      Lagrangian particle-based method, smoothed particle hydrodynamics (SPH), to study
      diffusion in biomolecular systems by numerically solving the time-dependent
      Smoluchowski equation for continuum diffusion. Unlike previous studies, a
      reactive Robin boundary condition (BC), rather than the absolute absorbing
      (Dirichlet) BC, is considered on the reactive boundaries. This new BC treatment
      allows for the analysis of enzymes with "imperfect" reaction rates. RESULTS: The
      numerical method is first verified in simple systems and then applied to the
      calculation of ligand binding to a mouse acetylcholinesterase (mAChE) monomer.
      Rates for inhibitor binding to mAChE are calculated at various ionic strengths
      and compared with experiment and other numerical methods. We find that imposition
      of the Robin BC improves agreement between calculated and experimental reaction
      rates. CONCLUSIONS: Although this initial application focuses on a single monomer
      system, our new method provides a framework to explore broader applications of
      SPH in larger-scale biomolecular complexes by taking advantage of its Lagrangian
      particle-based nature.

PMID- 25995836
TI  - Stability of operational taxonomic units: an important but neglected property for
      analyzing microbial diversity.
AB  - BACKGROUND: The operational taxonomic unit (OTU) is widely used in microbial
      ecology. Reproducibility in microbial ecology research depends on the reliability
      of OTU-based 16S ribosomal subunit RNA (rRNA) analyses. RESULTS: Here, we report
      that many hierarchical and greedy clustering methods produce unstable OTUs, with
      membership that depends on the number of sequences clustered. If OTUs are
      regenerated with additional sequences or samples, sequences originally assigned
      to a given OTU can be split into different OTUs. Alternatively, sequences
      assigned to different OTUs can be merged into a single OTU. This OTU instability
      affects alpha-diversity analyses such as rarefaction curves, beta-diversity
      analyses such as distance-based ordination (for example, Principal Coordinate
      Analysis (PCoA)), and the identification of differentially represented OTUs. Our
      results show that the proportion of unstable OTUs varies for different clustering
      methods. We found that the closed-reference method is the only one that produces
      completely stable OTUs, with the caveat that sequences that do not match a pre
      existing reference sequence collection are discarded. CONCLUSIONS: As a
      compromise to the factors listed above, we propose using an open-reference method
      to enhance OTU stability. This type of method clusters sequences against a
      database and includes unmatched sequences by clustering them via a relatively
      stable de novo clustering method. OTU stability is an important consideration
      when analyzing microbial diversity and is a feature that should be taken into
      account during the development of novel OTU clustering methods.

PMID- 25995837
TI  - X-ray lasers and serial crystallography.
AB  - A summary is given of the achievements and opportunities which resulted from the
      first use of an X-ray laser for serial crystallography and related methods in
      2009. 

PMID- 25995838
TI  - Powder to become crystal clear.
AB  - A simulation by Zhang et al. [IUCrJ (2015), 2, 322-326] has demonstrated that
      utilizing serial crystallography may turn one-dimensional powder diffraction from
      multiphase polycrystalline samples into three-dimensional single-crystal
      diffraction patterns. 

PMID- 25995839
TI  - Operational properties of fluctuation X-ray scattering data.
AB  - X-ray scattering images collected on timescales shorter than rotation diffusion
      times using a (partially) coherent beam result in a significant increase in
      information content in the scattered data. These measurements, named fluctuation
      X-ray scattering (FXS), are typically performed on an X-ray free-electron laser
      (XFEL) and can provide fundamental insights into the structure of biological
      molecules, engineered nanoparticles or energy-related mesoscopic materials beyond
      what can be obtained with standard X-ray scattering techniques. In order to
      understand, use and validate experimental FXS data, the availability of basic
      data characteristics and operational properties is essential, but has been absent
      up to this point. In this communication, an intuitive view of the nature of FXS
      data and their properties is provided, the effect of FXS data on the derived
      structural models is highlighted, and generalizations of the Guinier and Porod
      laws that can ultimately be used to plan experiments and assess the quality of
      experimental data are presented. 

PMID- 25995840
TI  - Second harmonic generation from the 'centrosymmetric' crystals.
AB  - Second harmonic generation (SHG) is a well known non-linear optical phenomena
      which can be observed only in non-centrosymmetric crystals due to non-zero
      hyperpolarizability. In the current work we observed SHG from a Zn(II) complex
      which was originally thought to have crystallized in the centrosymmetric space
      group C2/c. This has been attributed to the unequal antiparallel packing of the
      metal complexes in the non-symmetric space group Cc or residual non
      centrosymmetry in C2/c giving rise to polarizability leading to strong SHG. The
      enhancement of SHG by UV light has been attributed to the increase in non
      centrosymmetry and hence polarity of packing due to strain induced in the
      crystals. The SHG signals measured from these crystals were as large as potassium
      dihydrogen phosphate crystals, KH2PO4 (KDP), and showed temperature dependence.
      The highest SHG efficiency was observed at 50 K. The SHG phenomenon was observed
      at broad wavelengths ranging from visible to below-red in these crystals. 

PMID- 25995841
TI  - SFX analysis of non-biological polycrystalline samples.
AB  - Serial femtosecond crystallography (SFX) is capable of collecting three
      dimensional single-crystal diffraction data using polycrystalline samples. This
      may dramatically enhance the power of X-ray powder diffraction. In this paper a
      test has been performed using simulated diffraction patterns. The test sample is
      a mixture of two zeolites with crystal grain sizes from 100 to 300 nm. X-ray
      diffraction snapshots by SFX were simulated and processed using the program suite
      CrystFEL. Identification according to the primitive unit-cell volume determined
      from individual snapshots was able to separate the whole set of snapshots into
      two subsets, which correspond to the two zeolites in the sample. Monte Carlo
      integration in CrystFEL was then applied to them separately. This led to two sets
      of three-dimensional single-crystal diffraction intensities, based on which
      crystal structures of the two zeolites were solved easily by direct methods
      implemented in the program SHELXD. 

PMID- 25995842
TI  - Likelihood of atom-atom contacts in crystal structures of halogenated organic
      compounds.
AB  - The likelihood of occurrence of intermolecular contacts in crystals of
      halogenated organic compounds has been analysed statistically using tools based
      on the Hirshfeld surface. Several families of small halogenated molecules
      (containing organic F, Cl, Br or I atoms) were analysed, based on chemical
      composition and aromatic or aliphatic character. The behaviour of crystal
      contacts was also probed for molecules containing O or N. So-called halogen
      bonding (a halogen making short interactions with O or N, or a pi interaction
      with C) is generally disfavoured, except when H is scarce on the molecular
      surface. Similarly, halogen?halogen contacts are more rare than expected, except
      for molecules that are poor in H. In general, the H atom is found to be the
      preferred partner of organic halogen atoms in crystal structures. On the other
      hand, C?C interactions in parallel pi-stacking have a high propensity to occur in
      halogenated aromatic molecules. The behaviour of the four different halogen
      species (F, Cl, Br, I) is compared in several chemical composition contexts. The
      analysis tool can be refined by distinguishing several types for a given chemical
      species, such as H atoms bound to O or C. Such distinction shows, for instance,
      that C-H?Cl and O-H?O are the preferred interactions in compounds containing both
      O and Cl. 

PMID- 25995843
TI  - Do carboximide-carboxylic acid combinations form co-crystals? The role of
      hydroxyl substitution on the formation of co-crystals and eutectics.
AB  - Carboxylic acids, amides and imides are key organic systems which provide
      understanding of molecular recognition and binding phenomena important in
      biological and pharmaceutical settings. In this context, studies of their mutual
      interactions and compatibility through co-crystallization may pave the way for
      greater understanding and new applications of their combinations. Extensive co
      crystallization studies are available for carboxylic acid/amide combinations, but
      only a few examples of carboxylic acid/imide co-crystals are currently observed
      in the literature. The non-formation of co-crystals for carboxylic acid/imide
      combinations has previously been rationalized, based on steric and computed
      stability factors. In the light of the growing awareness of eutectic mixtures as
      an alternative outcome in co-crystallization experiments, the nature of various
      benzoic acid/cyclic imide combinations is established in this paper. Since an
      additional functional group can provide sites for new intermolecular inter
      actions and, potentially, promote supramolecular growth into a co-crystal,
      benzoic acids decorated with one or more hydroxyl groups have been systematically
      screened for co-crystallization with one unsaturated and two saturated cyclic
      imides. The facile formation of an abundant number of hydroxybenzoic acid/cyclic
      carboximide co-crystals is reported, including polymorphic and variable
      stoichiometry co-crystals. In the cases where co-crystals did not form, the
      combinations are shown invariably to result in eutectics. The presence or absence
      and geometric disposition of hydroxyl functionality on benzoic acid is thus found
      to drive the formation of co-crystals or eutectics for the studied carboxylic
      acid/imide combinations. 

PMID- 25995844
TI  - A posteriori determination of the useful data range for small-angle scattering
      experiments on dilute monodisperse systems.
AB  - Small-angle X-ray and neutron scattering (SAXS and SANS) experiments on solutions
      provide rapidly decaying scattering curves, often with a poor signal-to-noise
      ratio, especially at higher angles. On modern instruments, the noise is partially
      compensated for by oversampling, thanks to the fact that the angular increment in
      the data is small compared with that needed to describe adequately the local
      behaviour and features of the scattering curve. Given a (noisy) experimental data
      set, an important question arises as to which part of the data still contains
      useful information and should be taken into account for the interpretation and
      model building. Here, it is demonstrated that, for monodisperse systems, the
      useful experimental data range is defined by the number of meaningful Shannon
      channels that can be determined from the data set. An algorithm to determine this
      number and thus the data range is developed, and it is tested on a number of
      simulated data sets with various noise levels and with different degrees of
      oversampling, corresponding to typical SAXS/SANS experiments. The method is
      implemented in a computer program and examples of its application to analyse the
      experimental data recorded under various conditions are presented. The program
      can be employed to discard experimental data containing no useful information in
      automated pipelines, in modelling procedures, and for data deposition or
      publication. The software is freely accessible to academic users. 

PMID- 25995845
TI  - Serial snapshot crystallography for materials science with SwissFEL.
AB  - New opportunities for studying (sub)microcrystalline materials with small unit
      cells, both organic and inorganic, will open up when the X-ray free electron
      laser (XFEL) presently being constructed in Switzerland (SwissFEL) comes online
      in 2017. Our synchrotron-based experiments mimicking the 4%-energy-bandpass mode
      of the SwissFEL beam show that it will be possible to record a diffraction
      pattern of up to 10 randomly oriented crystals in a single snapshot, to index the
      resulting reflections, and to extract their intensities reliably. The crystals
      are destroyed with each XFEL pulse, but by combining snapshots from several sets
      of crystals, a complete set of data can be assembled, and crystal structures of
      materials that are difficult to analyze otherwise will become accessible. Even
      with a single shot, at least a partial analysis of the crystal structure will be
      possible, and with 10-50 femtosecond pulses, this offers tantalizing
      possibilities for time-resolved studies. 

PMID- 25995846
TI  - X-ray imaging detectors for synchrotron and XFEL sources.
AB  - Current trends for X-ray imaging detectors based on hybrid and monolithic
      detector technologies are reviewed. Hybrid detectors with photon-counting pixels
      have proven to be very powerful tools at synchrotrons. Recent developments
      continue to improve their performance, especially for higher spatial resolution
      at higher count rates with higher frame rates. Recent developments for X-ray free
      electron laser (XFEL) experiments provide high-frame-rate integrating detectors
      with both high sensitivity and high peak signal. Similar performance improvements
      are sought in monolithic detectors. The monolithic approach also offers a lower
      noise floor, which is required for the detection of soft X-ray photons. The link
      between technology development and detector performance is described briefly in
      the context of potential future capabilities for X-ray imaging detectors. 

PMID- 25995847
TI  - Availability and utilization of the WHO recommended priority lifesaving medicines
      for under five-year old children in public health facilities in Uganda: a cross
      sectional survey.
AB  - OBJECTIVES: To explore the availability and utilization of the World Health
      Organization (WHO) recommended priority life-saving medicines for children under
      five in public health facilities in Uganda. METHODS: We conducted a cross
      sectional survey in 32 lower level public facilities in Jinja district of Uganda.
      A proportionate number of facilities were randomly selected in each stratum
      following a hierarchy of Health Centers (HC) defined according to the level of
      care they provide: 17 HC IIs, 10 HC IIIs and 5 HC IVs. In the facilities, we
      verified the availability of the WHO recommended priority medicines for diarrhea,
      sepsis, pneumonia and malaria. 81 health workers from the facilities reported
      what they prescribed for children with the above diseases. RESULTS: Oral
      rehydration salt (ORS) and zinc sulphate dispersible tablets for diarrhea were
      available in all HC IIs and IIIs and in only 60% of HC IVs. Procaine benzyl
      penicillin injection powder for treatment of sepsis was available in the majority
      of all HCs with: 100% of HC of IVs, 83% of HC IIIs and 82% of HC IIs. Medicines
      for pneumonia were limited across all the HCs with: Amoxicillin dispersible
      tablets in only 30% of the HC IIs and 40% of the HC IVs. The most uncommon were
      child-friendly priority medicines for malaria with: Artesunate injection in only
      6% of HC IIs, 14% of HC IIIs and 20% of HC IVs; Artemether lumefantrine
      dispersible tablets and rectal artesunate were missing in all the 32 HCs. Less
      than a third of the health workers reported prescribing zinc sulphate and ORS for
      diarrhea, 86% reported procaine benzyl penicillin injection powder for sepsis,
      and 57% reported amoxicillin dispersible tablets for pneumonia. None reported
      prescribing Artemether lumefantrine dispersible tablets and rectal artesunate for
      malaria. CONCLUSIONS: There is low availability and utilization of life-saving
      priority medicines for pneumonia and malaria in public health facilities in
      Uganda. However, the priority medicines for diarrhea and sepsis are available and
      highly prescribed by the health workers.

PMID- 25995848
TI  - Carbon monoxide poisoning-induced cardiomyopathy from charcoal at a barbecue
      restaurant: a case report.
AB  - OBJECTIVE: Acute carbon monoxide poisoning has important clinical value because
      it can cause severe adverse cardiovascular effects and sudden death. Acute carbon
      monoxide poisoning due to charcoal is well reported worldwide, and increased use
      of charcoal in the restaurant industry raises concern for an increase in
      occupational health problems. We present a case of carbon monoxide poisoning
      induced cardiomyopathy in a 47-year-old restaurant worker. MATERIALS AND METHODS:
      A male patient was brought to the emergency department to syncope and complained
      of left chest pain. Cardiac angiography and electrocardiography were performed to
      rule out acute ischemic heart disease, and cardiac markers were checked. After
      relief of the symptoms and stabilization of the cardiac markers, the patient was
      discharged without any complications. RESULTS: Electrocardiography was normal,
      but cardiac angiography showed up to a 40% midsegmental stenosis of the right
      coronary artery with thrombotic plaque. The level of cardiac markers was elevated
      at least 5 to 10 times higher than the normal value, and the carboxyhemoglobin
      concentration was 35% measured at one hour after syncope. Following the diagnosis
      of acute carbon monoxide poisoning induced cardiomyopathy, the patient's medical
      history and work exposure history were examined. He was found to have been
      exposed to burning charcoal constantly during his work hours. CONCLUSIONS: Severe
      exposure to carbon monoxide was evident in the patient because of high
      carboxyhemoglobin concentration and highly elevated cardiac enzymes. We concluded
      that this exposure led to subsequent cardiac injury. He was diagnosed with acute
      carbon monoxide poisoning-induced cardiomyopathy due to an unsafe working
      environment. According to the results, the risk of exposure to noxious chemicals
      such as carbon monoxide by workers in the food service industry is potentially
      high, and workers in this sector should be educated and monitored by the
      occupational health service to prevent adverse effects.

PMID- 25995849
TI  - Synthese et etude structurale de Na9Cr(MoO4)6.
AB  - The title compound, nona-sodium chromium(III) hexa-kis[molybdate(VI)],
      Na9Cr(MoO4)6 was prepared by solid-state reactions. The basic structure units are
      isolated polyhedral clusters composed of a central CrO6 octa-hedron sharing
      vertices with six MoO4 tetrahedra to form an open framework in which the Na(+)
      cations are bound to the free vertices of the MoO4 tetra-hedra. The Cr(3+) cation
      has site symmetry of 32 (6a), one Na atom sits on a twofold axis (18e), and all
      other atoms are at general positions. The bond-valance-sum model confirms the
      expected values of ion charges. The title compound is isotypic with Na9Sc(MoO4)6
      and Na9Fe(MoO4)6. It is compared and discussed with similar structures. 

PMID- 25995850
TI  - Crystal structure of bis-[N-phenyl-2-(1,2,3,4-tetrahydronaphthalen-1
      ylidene)hydrazinecarbothio-amidato-kappa(2) N (2),S]zinc dimethyl sulfoxide
      monosolvate.
AB  - The reaction of the N-phenyl-2-(1,2,3,4-tetrahydronaphthalen-1-yl-idene)hy-dra
      zine-car-bo-thio-amide ligand with zinc acetate dihydrate in a 2:1 molar ratio
      yielded a yellow solid, which was crystallized from DMSO to obtain the title
      compound, [Zn(C17H16N3S)2].C2H6OS. The Zn(II) ion is four-coordinated in a
      distorted tetra-hedral environment by two deprotonated ligands. Each ligand acts
      as an N,S-donor, forming a five-membered metallacycle. The maximum deviation from
      the mean plane of the N-N-C-S chelate group is 0.0029 (14) A for the N-donor atom
      of one ligand and 0.0044 (14) A for the non-coordinating N atom of the second.
      The dihedral angle between the planes of the two chelate groups is 72.80 (07)
      degrees . Bond lengths in the ligands are compared with those in the crystal
      structure of the free ligand. In the crystal, complex mol-ecules are connected by
      dimethyl sulfoxide solvate mol-ecules via N-H?O hydrogen-bonding inter-actions,
      building a one-dimensional hydrogen-bonded polymer along the a-axis direction.
      The S atom and one C atom of the dimethyl sulfoxide solvate mol-ecules are
      disordered over two sets of sites with an occupancy ratio of 0.6:0.4. 

PMID- 25995851
TI  - Crystal structure of [bis-(2,6-diiso-propyl-phen-yl) phosphato-kappaO]tris
      (methanol-kappaO)lithium methanol monosolvate.
AB  - Crystals of the title compound, [Li{OOP(O-2,6-(i)Pr2C6H3)2}(CH3OH)3].CH3OH or
      [Li(C24H34O4P)(CH3OH)3].CH3OH, have been formed in the reaction between HOOP(O
      2,6-(i)Pr2C6H3)2 and LiOH in methanol. The title compound is of inter-est as it
      represents the first reported crystal structure of the family of lithium
      phosphate diesters. The {Li(CH3OH)3[O2P(O-(i)Pr2C6H3)2]} unit displays the Li
      atom in a slightly distorted tetra-hedral coordination environment and exhibits
      one intra-molecular O-H?O hydrogen bond between a coordinating methanol mol-ecule
      and the terminal non-coordinating O atom of the phosphate group. The unit is
      connected with two non-coordinating methanol mol-ecules through two inter
      molecular O-H?O hydrogen bonds, and with a neighbouring unit through two other O
      H?O inter-actions. These inter-molecular hydrogen bonds lead to the formation of
      infinite chains along [100]. There are no significant inter-actions between the
      chains. 

PMID- 25995708
TI  - Search for direct pair production of a chargino and a neutralino decaying to the
      125 GeV Higgs boson in [Formula: see text] TeV [Formula: see text] collisions
      with the ATLAS detector.
AB  - A search is presented for the direct pair production of a chargino and a
      neutralino [Formula: see text], where the chargino decays to the lightest
      neutralino and the [Formula: see text] boson, [Formula: see text], while the
      neutralino decays to the lightest neutralino and the 125 GeV Higgs boson,
      [Formula: see text]. The final states considered for the search have large
      missing transverse momentum, an isolated electron or muon, and one of the
      following: either two jets identified as originating from bottom quarks, or two
      photons, or a second electron or muon with the same electric charge. The analysis
      is based on 20.3 [Formula: see text] of [Formula: see text] proton-proton
      collision data delivered by the Large Hadron Collider and recorded with the ATLAS
      detector. Observations are consistent with the Standard Model expectations, and
      limits are set in the context of a simplified supersymmetric model.

PMID- 25995852
TI  - Crystal structures of di-chlorido-palladium(II), -platinum(II) and -rhodium(III)
      complexes containing 8-(di-phenyl-phosphan-yl)quinoline.
AB  - The crystal structures of di-chlorido-palladium(II), -platinum(II) and 
      rhodium(III) complexes containing 8-(di-phenyl-phosphan-yl)quinoline, (SP-4)
      [PdCl2(C21H16NP)], (1) [systematic name: di-chlor-ido-(8-di-phenyl-phosphanyl
      quinoline)-palladium(II)], (SP-4)-[PtCl2(C21H16NP)].CH2Cl2, (2) [systematic name:
      di-chlorido-(8-di-phenyl-phos-phanyl-quinoline)-platinum(II) dichlorometh-ane
      monosolvate], and (OC-6-32)-[RhCl2(C21H16NP)2]PF6.0.5CH2Cl2.0.5CH3OH, (3)
      [systematic name: cis-di-chlor-ido-bis-(8-di-phenyl-phosphanyl-quinoline)
      rhodium(III) hexa-fluorido-phos-phate di-chloro-methane/-methanol hemisolvate]
      are reported. In these complexes, the phosphanyl-quinoline acts as a bidentate
      ligand, forming a planar asymmetrical five-membered chelate ring. The
      palladium(II) and platinum(II) complex mol-ecules in (1) and (2), respectively,
      show a typical square-planar coordination geometry and form a dimeric structure
      through an inter-molecular pi-pi stacking inter-action between the quinolyl
      rings. The centroid-centroid distances between the stacked six-membered rings in
      (1) and (2) are 3.633 (2) and 3.644 (2) A, respectively. The cationic
      rhodium(III) complex in (3) has a cis(Cl),cis(P),cis(N) (OC-6-32) configuration
      of the ligands, in which two kinds of intra-molecular pi-pi stacking inter
      actions are observed: between the quinolyl and phenyl rings and between two
      phenyl rings, the centroid-centroid distances being 3.458 (2) and 3.717 (2) A,
      respectively. The PF6 (-) anion in (3) is rotationally disordered, the site
      occupancies of each F atom being 0.613 (14) and 0.387 (14). The CH2Cl2 and CH3OH
      solvent mol-ecules are also disordered and equal site occupancies of 0.5 are
      assumed. 

PMID- 25995854
TI  - Le nitrate double NaRb2(NO3)3, compose intermediaire du systeme binaire isobare
      NaNO3 + RbNO3: etudes thermiques et cristallographiques.
AB  - Crystallographic and thermodynamic investigations of the binary (NaNO3 + RbNO3)
      phase diagram at atmospheric pressure reveal the existence of an inter-mediate
      compound NaRb2(NO3)3 (sodium dirubidium trinitrate) previously predicted and now
      reported experimentally for the first time. According to a DSC analysis, the
      compound exhibits three allotropic forms. In its low-temperature allotropic form
      (alpha form, ortho-rhom-bic) there are two Rb (m.. site symmetry) and one Na
      (m..) independent crystallographic positions and three planar nitrate groups. The
      bond-valence-sum calculations for all atoms agree well with their oxidation
      states. The Rb cations are located in the (100) plane at x = 1/2 with 11 oxygen
      coordination. The Na ones are in the same plane at x = 0 and are coordinated to
      eight O atoms from six nitrate groups. The charge-distribution method has been
      used to evaluate the degree of distortion of the alkali polyhedra. 

PMID- 25995853
TI  - Crystal structure of bis-(azido-kappaN)bis[2,5-bis(pyridin-2-yl)-1,3,4-thia
      diazole-kappa(2) N (2),N (3)]cobalt(II).
AB  - In the mononuclear title complex, [Co(N3)2(C12H8N4S)2], the cobalt(II) atom is
      located on an inversion centre and displays an axially weakly compressed octa
      hedral coordination geometry. The equatorial positions are occupied by the N
      atoms of two 2,5-bis-(pyridin-2-yl)-1,3,4-thia-diazole ligands, whereas the axial
      positions are occupied by N atoms of the azide anions. The thia-diazole and
      pyridine rings linked to the metal are almost coplanar, with a maximum deviation
      from the mean plane of 0.0273 (16) A. The cohesion of the crystal is ensured by
      weak C-H?N hydrogen bonds and by pi-pi inter-actions between pyridine rings
      [inter-centroid distance = 3.6356 (11) A], forming a layered arrangement parallel
      to (001). The structure of the title compound is isotypic with that of the
      analogous nickel(II) complex [Laachir et al. (2013 ?). Acta Cryst. E69, m351
      m352]. 

PMID- 25995855
TI  - Crystal structure of poly[MU2-aqua-aqua-(MU2-4-nitro-2,5,6-trioxo-1,2,5,6-tetra
      hydro-pyridin-3-olato)hemi-MU4-oxalato-barium(II)].
AB  - In the title coordination polymer, [Ba(C5HN2O6)(C2O4)0.5(H2O)2] n , the tenfold
      coordination of the Ba centre consists of four O atoms from the two 4-nitro-2,5,6
      trioxo-1,2,5,6-tetra-hydro-pyridin-3-olate (L) anions, three O atoms of two
      oxalate anions and three water mol-ecules. The Ba-O bond lengths fall in the
      range 2.698 (3)-2.978 (3) A. The L ligand chelates two Ba atoms related by a
      screw axis, leading to formation of fused five- and six-membered chelate rings.
      Due to the bridging function of the ligands and water mol-ecules, the complex
      monomers are connected into polymeric two-dimensional layers parallel to the bc
      plane. Inter-molecular O-H?O hydrogen bonds link these layers into a three
      dimensional supra-molecular framework. 

PMID- 25995862
TI  - Crystal structure of (Z)-N'-[1-(3-methyl-5-oxo-1-phenyl-1,5-di-hydro-4H-pyrazol-4
      yl-idene)prop-yl]benzene-sulfono-hydrazide.
AB  - The title compound, C19H20N4O3S, was synthesized by refluxing equimolar amounts
      of 1-phenyl-3-methyl-4-propionylpyrazol-5-one and benzene-sulfonyl hydrazide in
      ethanol. The compound crystallizes in the keto form and the carbonyl O atom forms
      an intra-molecular N-H?O hydrogen bond with the neighbouring NH group. There is
      also C-H?O short contact involving the neighbouring phenyl ring. Probably as a
      result of this, the phenyl ring is inclined to the pyrazolone ring by only 7.58
      (12) degrees . The dihedral angle between the phenyl ring and the benzene
      sulfonyl ring is 22.78 (11) degrees . In the crystal, mol-ecules are linked by
      pairs of N-H?O hydrogen bonds, forming inversion dimers with an R (2) 2(14) ring
      motif. The dimers are linked via pairs of C-H?O hydrogen bonds, forming chains
      propagating along [100]. 

PMID- 25995857
TI  - Crystal structures of (+/-)-(1SR,5SR,6SR,7SR,10SR,11SR,13RS,14SR)-13-hy-droxy-7
      meth-oxy-meth-oxy-11,15,18,18-tetra-methyl-3-oxo-2,4-dioxa-tetra-cyclo
      [12.3.1.0(1,5).0(6,11)]octa-dec-15-en-10-yl benzoate, its 13-epimer and 13-one
      derivative.
AB  - The title compounds, C29H38O8.0.25C5H12, (A), C29H38O8, (B), and C29H36O8, (C),
      are tetra-cyclic benzoates possessing a taxane skeleton with a fused dioxolane
      ring as the core structure. In the asymmetric unit of (A), there are two
      independent benzoate mol-ecules (A and A') and a half mol-ecule of solvent
      pentane disordered about an inversion center. The mol-ecular conformations of
      (A), (B) and (C) are similar except for the flexible meth-oxy-meth-oxy group. The
      cyclo-hexane, cyclo-hexene and central cyclo-octane rings adopt chair, half-chair
      and chair-chair (extended crown) forms, respectively. The dioxolane rings are
      essentially planar, while the dioxolane ring of A' is slightly twisted from the
      mean plane. In the crystal of (A), inter-molecular O-H?O, C-H?O and C-H?pi inter
      actions link the independent benzoates alternately, forming a chain structure. In
      the crystals of (B) and (C), mol-ecules are linked through O-H?O and C-H?pi inter
      actions, and C-H?O hydrogen bonds, respectively, into similar chains. Further,
      weak inter-molecular C-H?O inter-actions connect the chains into a three
      dimensional network in (A) and a sheet in (B), whereas no other interactions are
      observed for (C). 

PMID- 25995861
TI  - Packing polymorphism in the crystal structure of 4,5-dimeth-oxy-2-nitro-benzyl
      acetate.
AB  - The title compound, C11H13NO6, shows two polymorphs, orange and yellow forms,
      both of which crystallize in the space group P21/c. The mol-ecular structures in
      the two polymorphs are essentially similar and adopt a planar structure, the
      maximum deviations for the non-H atoms being 0.1836 (13) and 0.1276 (13) A,
      respectively, for the orange and yellow forms. In the orange crystal, mol-ecules
      are linked by an inter-molecular C-H?O inter-action into a helical chain along
      the b-axis direction. The chains are stacked along the c axis through a pi-pi
      inter-action [centroid-centroid distance = 3.6087 (11) A], forming a layer
      parallel to the bc plane. In the yellow crystal, mol-ecules are connected through
      C-H?O inter-actions into a sheet structure parallel to (-302). No significant pi
      pi inter-action is observed. The unit-cell volume of the orange crystal is larger
      than that of the yellow one, and this accounts for the predominant growth of the
      yellow crystal. 

PMID- 25995860
TI  - Crystal structure of poly[bis-(MU-nicotinamide-kappa(2) N (1):O)bis-(MU-4-nitro
      benzoato-kappa(2) O (1):O (1'))zinc].
AB  - The asymmetric unit of the title coordination polymer, [Zn(C7H4NO4)2(C6H6N2O)2] n
      , contains two 4-nitro-benzoate (NB) anions and two nicotinamide (NA) ligands.
      The Zn(II) atom has a slightly distorted octa-hedral coordination sphere. In the
      equatorial plane, it is coordinated by three carboxyl-ate O atoms of the NB
      anions and one O atom of one of the two NA ligands. The axial positions are
      occupied by the pyridine N atoms of the two NA ligands. In the two NB anions, the
      carboxyl-ate groups are twisted away from the attached benzene rings by 13.8 (2)
      and 13.4 (2) degrees , while the benzene rings are oriented at a dihedral angle
      of 11.5 (2) degrees . The dihedral angle between the NA rings is 10.3 (1) degrees
      . Only one of the two NB anions and one of the two NA ligands bridge adjacent
      Zn(II) ions through eight- and twelve-membered rings, respectively, forming
      polymeric chains running along the a-axis direction. In the crystal, N-H ? O
      hydrogen bonds link adjacent chains, enclosing R(16), R 2 (2)(20) and R 6 (6)(16)
      ring motifs, forming layers parallel to (01-1). The layers are linked via a
      number of C-H?O hydrogen bonds, forming a three-dimensional network. 

PMID- 25995858
TI  - Crystal structure of di-methyl-ammonium hydrogen oxalate hemi(oxalic acid).
AB  - Single crystals of the title salt, Me2NH2 (+).HC2O4 (-).0.5H2C2O4, were isolated
      as a side product from the reaction involving Me2NH, H2C2O4 and Sn(n-Bu)3Cl in a
      1:2 ratio in methanol or by the reaction of the (Me2NH2)2C2O4 salt and Sn(CH3)3Cl
      in a 2:1 ratio in ethanol. The asymmetric unit comprises a di-methyl-ammonium
      cation (Me2NH2 (+)), an hydrogenoxalate anion (HC2O4 (-)), and half a mol-ecule
      of oxalic acid (H2C2O4) situated about an inversion center. From a supra
      molecular point of view, the three components inter-act together via hydrogen
      bonding. The Me2NH2 (+) cations and the HC2O4 (-) anions are in close proximity
      through bifurcated N-H?(O,O) hydrogen bonds, while the HC2O4 (-) anions are
      organized into infinite chains via O-H?O hydrogen bonds, propagating along the a
      axis direction. In addition, the oxalic acid (H2C2O4) mol-ecules play the role of
      connectors between these chains. Both the carbonyl and hydroxyl groups of each
      diacid are involved in four inter-molecular inter-actions with two Me2NH2 (+) and
      two HC2O4 (-) ions of four distinct polymeric chains, via two N-H?O and two O-H?O
      hydrogen bonds, respectively. The resulting mol-ecular assembly can be viewed as
      a two-dimensional bilayer-like arrangement lying parallel to (010), and
      reinforced by a C-H?O hydrogen bond. 

PMID- 25995864
TI  - Crystal structure of a polymeric calcium levulinate dihydrate: catena-poly[[di
      aqua-calcium]-bis-(MU2-4-oxo-butano-ato)].
AB  - In the title calcium levulinate complex, [Ca(C5H7O3)2(H2O)2] n , the Ca(2+) ion
      lies on a twofold rotation axis and is octa-coordinated by two aqua ligands and
      six O atoms from four symmetry-related carboxyl-ate ligands, giving a distorted
      square-anti-prismatic coordination stereochemistry [Ca-O bond-length range =
      2.355 (1)-2.599 (1) A]. The levulinate ligands act both in a bidentate carboxyl
      O,O'-chelate mode and in a bridging mode through one carboxyl O atom with an
      inversion-related Ca(2+) atom, giving a Ca?Ca separation of 4.0326 (7) A. A
      coordination polymeric chain structure is generated, extending along the c-axial
      direction. The coordinating water mol-ecules act as double donors and participate
      in intra-chain O-H?O hydrogen bonds with carboxyl O atoms, and in inter-chain O
      H?O hydrogen bonds with carbonyl O atoms, thus forming an overall three
      dimensional structure. 

PMID- 25995856
TI  - Crystal structure of the co-crystalline adduct 1,3,6,8-tetra-aza-tri-cyclo
      [4.4.1.1(3,8)]dodecane (TATD)-4-bromo-phenol (1/2).
AB  - The structure of the 1:2 co-crystalline adduct C8H16N4.2C6H5BrO, (I), from the
      solid-state reaction of 1,3,6,8-tetra-aza-tri-cyclo-[4.4.1.1(3,8)]dodecane (TATD)
      and 4-bromo-phenol, has been determined. The asymmetric unit of the title co
      crystalline adduct comprises a half mol-ecule of aminal cage polyamine plus a 4
      bromo-phenol mol-ecule. A twofold rotation axis generates the other half of the
      adduct. The primary inter-species association in the title compound is through
      two inter-molecular O-H?N hydrogen bonds. In the crystal, the adducts are linked
      by weak non-conventional C-H?O and C-H?Br hydrogen bonds, giving a two
      dimensional supra-molecular structure parallel to the bc plane. 

PMID- 25995859
TI  - Crystal structure of 2,4-di-amino-6-oxo-3,6-di-hydro-pyrimidin-1-ium p-toluene
      sulfonate.
AB  - In the title salt, C4H7N4O(+).C7H7O3S(-), the 2,6-di-amino-4-oxo-1,3-di-hydro
      pyrimidin-1-ium cation inter-acts with the sulfonate group of the p-toluene
      sulfonate anion via a pair of N-H?O hydrogen bonds, forming a hetero-synthon R 2
      (2)(8) that mimics the role of a carboxyl-ate. The self-assembled cations form a
      homo-synthon R 2 (1)(6) motif which is further linked with the sulfonate anion
      via N-H?O hydrogen bonds to generate an R 3 (2)(10) ring motif. The three motifs
      are fused together and extended as supra-molecular ribbons along the b-axis
      direction. Adjacent ribbons are further linked via N-H?O hydrogen bonds to form
      an annulus, with an R 4 (4)(20) ring motif, resulting in a tunnel-like
      arrangement propagating along [010]. There are slipped parallel pi-pi stacking
      inter-actions [inter-centroid distance = 3.6539 (7) A], between the tunnel-like
      polymer chains, forming slabs parallel to (100). 

PMID- 25995865
TI  - Crystal structure of a new hybrid anti-mony-halide-based compound for possible
      non-linear optical applications.
AB  - The hybrid title compound, catena-poly[[[bis-(1,4-diazo-niabi-cyclo-[2.2.2]octa
      ne) [tetra-achlorido-anti-monate(III)]-MU-chlorido-[tetra-chlorido-anti
      monate(III)]-MU-chlorido]] monohydrate], {(C6H14N2)2[Sb2Cl10].H2O} n , is self
      assembled into alternating organic and inorganic layers parallel to the bc plane.
      The anionic inorganic layer consists of infinite zigzag chains of corner-sharing
      [SbCl6](3-) octa-hedra running along the b axis. The organic part is made up of
      1,4-diazo-niabi-cyclo-[2.2.2]octane dications (dabcoH2 (2+)). The water mol
      ecules in the structure connect inorganic and organic layers. Hydrogen-bonding
      inter-actions between the ammonium groups, water mol-ecules and Cl atoms ensure
      the structure cohesion. 

PMID- 25995863
TI  - Crystal structure of (+/-)-(1SR,5SR,6SR,7SR,10SR,11SR,13SR)-13-benz-yloxy-7-meth
      oxy-meth-oxy-11,15,18,18-tetra-methyl-3-oxo-2,4-dioxa-tetra-cyclo
      [12.3.1.0(1,5).0(6,11)]octa-deca-14,16-dien-10-yl benzoate.
AB  - In the title compound, C36H42O8, the dioxolane ring adopts a twist conformation;
      the two adjacent C atoms deviate alternately from the mean plane of other atoms
      by -0.287 (5) and 0.174 (5) A. The cyclo-hexane, cyclo-hexa-diene and central
      cyclo-octane rings show chair, half-chair and boat-chair forms, respectively. As
      a result of the strained ring system, the tetra-subsituted olefin in the cyclo
      hexa-diene is skewed from an ideal planar structure. In the crystal, C-H?O
      hydrogen bonds connect the mol-ecules into a sheet parallel to (100). The sheets
      are further linked by other weak C-H?O and C-H?pi inter-actions, forming a three
      dimensional network. 

PMID- 25995867
TI  - Crystal structure of 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxa-diazol-3-yl)phen
      oxy]prop-yl}-N-(11-hy-droxy-undec-yl)isoxazole-3-carboxamide hemihydrate.
AB  - The title compound, C29H42N4O5.0.5H2O, comprises four structural units. A
      flexible prop-yloxy unit in a gauche conformation, with a -C(H2)-C(H2)-C(H2)-O-
      torsion angle of -64.32 (18) degrees , connects an isoxazole ring and an
      approximately planar phenyl-oxa-diazole ring system [with a maxixmum devation of
      0.061 (2) A], which are oriented almost parallel to one another with a dihedral
      angle of 10.75 (7) degrees . Furthermore, a C11-alkyl chain with a terminal hy
      droxy group links to the 3-position of the isoxazole ring via an amide bond. In
      the crystal, a half-occupancy solvent water mol-ecule connects to a neighbouring
      mol-ecule via an inter-molecular O-H?O(water) hydrogen bond to the C11-alkyl
      chain hy-droxy group. 

PMID- 25995866
TI  - Crystal structure of SrGeO3 in the high-pressure perovskite-type phase.
AB  - Single crystals of the SrGeO3 (strontium germanium trioxide) high-pressure phase
      have been synthesized successfully at 6 GPa and 1223 K. The compound crystallizes
      with the ideal cubic perovskite-type structure (space group Pm-3m), which
      consists of a network of corner-linked regular GeO6 octa-hedra (point-group
      symmetry m-3m), with the larger Sr atoms located at the centers of cavities in
      the form of SrO12 cubocta-hedra (point-group symmetry m-3m) in the network. The
      degrees of covalencies included in the Sr-O and the Ge-O bonds calculated from
      bond valences are 20.4 and 48.9%, respectively. Thus, the Ge-O bond of the GeO6
      octa-hedron in the SrGeO3 perovskite has a strong covalency, comparable to those
      of the Si-O bonds of the SiO4 tetra-hedra in silicates with about 50% covalency.
      The thermal vibrations of the O atoms in the title compound are remarkably
      suppressed in the directions of the Ge-O bonds. This anisotropy ranks among the
      largest observed in stoichiometric cubic perovskites. 

PMID- 25995868
TI  - Crystal structures of 2,2'-bipyridin-1-ium 1,1,3,3-tetracyano-2-ethoxyprop-2-en-1
      ide and bis(2,2'-bipyridin-1-ium) 1,1,3,3-tetracyano-2-(dicyanomethylene)propane
      1,3-diide.
AB  - In 2,2'-bipyridin-1-ium 1,1,3,3-tetra-cyano-2-eth-oxy-prop-2-en-1-ide, C10H9N2
      (+).C9H5N4O(-), (I), the ethyl group in the anion is disordered over two sets of
      atomic sites with occupancies 0.634 (9) and 0.366 (9), and the dihedral angle
      between the ring planes in the cation is 2.11 (7) degrees . The two independent
      C(CN)2 groups in the anion make dihedral angles of 10.60 (6) and 12.44 (4)
      degrees  with the central propenide unit, and the bond distances in the anion
      provide evidence for extensive electronic delocalization. In bis-(2,2'-bipyridin
      1-ium) 1,1,3,3-tetra-cyano-2-(di-cyano-methyl-ene)propane-1,3-diide [alternative
      name bis-(2,2'-bipyridin-1-ium) tris-(di-cyano-methyl-ene)methane-diide],
      2C10H9N2 (+).C10N6 (2-) (II), the dihedral angles between the ring planes in the
      two independent cations are 7.7 (2) and 10.92 (17) degrees . The anion exhibits
      approximate C 3 symmetry, consistent with extensive electronic delocalization,
      and the three independent C(CN)2 groups make dihedral angles of 23.8 (2), 27.0
      (3) and 27.4 (2) degrees  with the central plane. The ions in (I) are linked by
      an N-H?N hydrogen bond and the resulting ion pairs are linked by two independent
      C-H?N hydrogen bonds, forming a ribbon containing alternating R 4 (4)(18) and R 4
      (4)(26) rings, where both ring types are centrosymmetric. The ions in (II) are
      linked by two independent N-H?N hydrogen bonds and the resulting ion triplets are
      linked by a C-H?N hydrogen bond, forming a C 2 (1)(7) chain containing anions and
      only one type of cation, with the other cation linked to the chain by a further C
      H?N hydrogen bond. 

PMID- 25995869
TI  - Crystal structure of rac-(3a'R,9a'R)-3a'-(indol-3-yl)-1',2',3',3a',4',9a'-hexa
      hydro-spiro-[cyclo-pentane-1,9'-penta-leno[1,2-b]indole] p-xylene hemisolvate.
AB  - The title compound, C26H26N2.0.5C8H10, is the first reported characterized 2:2
      product from acid-catalyzed condensation of indole with cyclo-penta-none and no
      other 2:2 products were observed. Recrystallization from p-xylene gave the title
      hemisolvate with the p-xylene mol-ecule located about an inversion center. The
      terminal penta-lene ring is envelope-flap disordered at the C atom farthest from
      the skeletal indole unit, with a refined occupancy ratio of 0.819 (4):0.181 (4).
      The major component has this C atom bent away from the spiro-fused cyclo-pentane
      ring. In the crystal, mol-ecules are connected by N-H?pi inter-actions, forming
      chains along [100], and N-H?pi and C-H?pi inter-actions, forming chains along
      [001], which results in the formation of slabs parallel to (010). 

PMID- 25995709
TI  - Search for production of [Formula: see text] resonances decaying to a lepton,
      neutrino and jets in [Formula: see text] collisions at [Formula: see text] TeV
      with the ATLAS detector.
AB  - A search is presented for narrow diboson resonances decaying to [Formula: see
      text] or [Formula: see text] in the final state where one [Formula: see text]
      boson decays leptonically (to an electron or a muon plus a neutrino) and the
      other [Formula: see text] boson decays hadronically. The analysis is performed
      using an integrated luminosity of 20.3 fb[Formula: see text] of [Formula: see
      text] collisions at [Formula: see text] TeV collected by the ATLAS detector at
      the large hadron collider. No evidence for resonant diboson production is
      observed, and resonance masses below 700 and 1490 GeV are excluded at 95 %
      confidence level for the spin-2 Randall-Sundrum bulk graviton [Formula: see text]
      with coupling constant of 1.0 and the extended gauge model [Formula: see text]
      boson respectively.

PMID- 25995870
TI  - Crystal structure of 2-methyl-1H-imidazol-3-ium aqua-tri-chlorido-(oxalato
      kappa(2) O,O')stannate(IV).
AB  - The tin(IV) atom in the complex anion of the title salt,
      (C4H7N2)[Sn(C2O4)Cl3(H2O)], is in a distorted octa-hedral coordination
      environment defined by three chlorido ligands, an oxygen atom from a water mol
      ecule and two oxygen atoms from a chelating oxalate anion. The organic cation is
      linked through a bifurcated N-H?O hydrogen bond to the free oxygen atoms of the
      oxalate ligand of the complex [Sn(H2O)Cl3(C2O4)](-) anion. Neighbouring
      stannate(IV) anions are linked through O-H?O hydrogen bonds involving the water
      mol-ecule and the two non-coordinating oxalate oxygen atoms. In combination with
      additional N-H?Cl hydrogen bonds between cations and anions, a three-dimensional
      network is spanned. 

PMID- 25995871
TI  - Crystal structures of 1-(4-chloro-phen-yl)-2-(di-phenyl-phosphor-yl)ethan-1-one
      and 1-(di-phenyl-phosphor-yl)-3,3-di-methyl-butan-2-one.
AB  - The title compounds, C20H16ClO2P, (I), and C18H21O2P, (II), were synthesized via
      an Arbuzov reaction between an alpha-bromo-ketone and isopropoxydi-phenyl
      phosphane. In the crystals of both compounds, mol-ecules are linked via
      bifurcated C-H?(O,O) hydrogen bonds, forming chains propagating along [100] for
      (I) and along [010] for (II). The chains are linked via C-H?pi inter-actions,
      leading to the formation of sheets lying parallel to (010) for (I) and (001) for
      (II). The absolute structure of compound (II) was determined by resonant
      scattering [Flack parameter = 0.088 (14)]. 

PMID- 25995872
TI  - Crystal structure of di-MU-chlorido-bis-[di-chlorido-bis-(methanol
      kappaO)iridium(III)] dihydrate: a surprisingly simple chlorido-iridium(III)
      dinuclear complex with methanol ligands.
AB  - The reaction between IrCl3.xH2O in methanol led to the formation of small amounts
      of the title compound, [Ir2Cl6(CH3OH)4].2H2O, which consists of two IrCl4O2 octa
      hedra sharing an edge via chloride bridges. The mol-ecule lies across an
      inversion center. Each octa-hedron can be envisioned as being comprised of four
      chloride ligands in the equatorial plane with methanol ligands in the axial
      positions. A lattice water mol-ecule is strongly hydrogen-bonded to the
      coordinating methanol ligands and weak inter-actions with coordinating chloride
      ligands lead to the formation of a three-dimensional network. This is a
      surprising structure given that, while many reactions of iridium chloride hydrate
      are carried out in alcoholic solvents, especially methanol and ethanol, this is
      the first structure of a chloridoiridium compound with only methanol ligands. 

PMID- 25995874
TI  - Crystal structure of bis-[4-(1H-pyrrol-1-yl)phen-yl] ferrocene-1,1'-di-carboxyl
      ate: a potential chemotherapeutic drug.
AB  - The title iron(II) complex, [Fe(C16H12NO2)2], crystallizes in the ortho-rhom-bic
      space group Pbca with the Fe(2+) cation positioned on an inversion center. The
      cyclo-penta-dienyl (Cp) rings adopt an anti conformation in contrast with other
      substituted ferrocenes in which the Cp rings appear in a nearly eclipsed
      conformation. The Cp and the aromatic rings are positioned out of the plane, with
      a twist angle of 70.20 (12) degrees , and the C(Cp)-C(CO) bond length is shorter
      than a typical C-C single bond, which suggests a partial double-bond character
      and delocalization with the Cp pi system. The structure of the complex is
      compared to other functionalized ferrocenes synthesized in our laboratory. 

PMID- 25995873
TI  - Crystal structure of 3-bromo-2-hy-droxy-benzoic acid.
AB  - Mutual carbox-yl-carboxyl O-H?O hydrogen bonds link the mol-ecules of the title
      compound, C7H5BrO3, into centrosymmetric dimers which display a central R 2
      (2)(8) ring motif. In addition, there is an intra-molecular hydrox-yl-carboxyl O
      H?O inter-action present. A comparison with the crystal structures of 59 other
      substituted derivatives of salicylic acid shows that both the centrosymmetric
      carbox-yl-carboxyl O-H?O dimer and the stacking mode of mol-ecules along the
      short a axis observed in the title structure are frequent packing motifs in this
      set. 

PMID- 25995875
TI  - Crystal structure of bis-[trans-(1,4,8,11-tetra-aza-cyclo-tetra-decane-kappa(4)
      N)bis-(thio-cyanato-kappaN)chromium(III)] tetra-chlorido-zincate from synchrotron
      data.
AB  - The structure of the title compound, [Cr(NCS)2(cyclam)]2[ZnCl4] (cyclam =
      1,4,8,11-tetra-aza-cyclo-tetra-decane, C10H24N4), has been determined from
      synchrotron data. The asymmetric unit contains two independent halves of the
      Cr(III) complex cations and half of a tetra-chlorido-zincate anion. In each
      complex cation, the Cr(III) atom is coordinated by the four N atoms of the cyclam
      ligand in the equatorial plane and by two N-bound NCS(-) anions in a trans axial
      arrangement, displaying a distorted octa-hedral geometry with crystallographic
      inversion symmetry. The mean Cr-N(cyclam) and Cr-N(NCS) bond lengths are 2.065
      (4) and 1.995 (6) A, respectively. The macrocyclic cyclam moieties adopt
      centrosymmetric trans-III configurations with six- and five-membered chelate
      rings in chair and gauche configurations, respectively. The [ZnCl4](2-) anion,
      which lies about a twofold rotation axis, has a slightly distorted tetra-hedral
      geometry. The crystal packing is stabilized by hydrogen-bonding inter-actions
      between the N-H groups of the cyclam ligands, the S atoms of the NCS(-) groups
      and the Cl(-) ligands of the anion. 

PMID- 25995876
TI  - Crystal structure of bis-[1,3-bis-(2,6-diiso-propyl-phen-yl)imidazol-2-yl
      idene]silver(I) chloride tetrahydro-furan monosolvate.
AB  - In the title salt, [Ag(C27H36N2)2]Cl.C4H8O, the Ag(I) atom is coordinated by two
      1,3-bis-(2,6-di-methyl-phen-yl)imidazol-2-yl-idene ligands. The imidazole rings
      are inclined to one another by 46.69 (13) degrees  and the benzene rings in each
      ligand are almost normal to the imdazole ring to which they are attached, with
      dihedral angles varying from 82.39 (13) to 88.27 (12) degrees . There are C-H?pi
      inter-actions present in the cation, involving the two ligands, and the solvent
      mol-ecule is linked to the cation via a C-H?O hydrogen bond. In the crystal, mol
      ecules are linked by trifurcated C-H?(Cl,Cl,Cl) hydrogen bonds, forming slabs
      parallel to (101). One isopropyl group is disordered over two sets of sites with
      an occupancy ratio of 0.447 (17):0.553 (17) and the THF mol-ecule is disordered
      over two positions with an occupancy ratio of 0.589 (6):0.411 (6). 

PMID- 25995877
TI  - New insights in the discovery of novel h-MAO-B inhibitors: structural
      characterization of a series of N-phenyl-4-oxo-4H-chromene-3-carboxamide
      derivatives.
AB  - Six N-substituted-phenyl 4-oxo-4H-chromene-3-carboxamides, namely N-(2-nitro-phen
      yl)-4-oxo-4H-chromene-3-carboxamide, C16H10N2O5 (2b), N-(3-meth-oxy-phen-yl)-4
      oxo-4H-chromene-3-carboxamide, C17H13NO4, (3a), N-(3-bromo-phen-yl)-4-oxo-4H
      chromene-3-carboxamide, C16H10BrNO3, (3b), N-(4-methoxy-phen-yl)-4-oxo-4H
      chromene-3-carboxamide, C17H13NO4, (4a), N-(4-methyl-phen-yl)-4-oxo-4H-chromene-3
      carboxamide, C17H13NO3, (4d), and N-(4-hy-droxy-phen-yl)-4-oxo-4H-chromene-3
      carboxamide, C16H11NO4, (4e), have been structurally characterized. All compounds
      exhibit an anti conformation with respect to the C-N rotamer of the amide and a
      trans-related conformation with the carbonyl groups of the chromone ring of the
      amide. These structures present an intra-molecular hydrogen-bonded network
      comprising an N-H?O hydrogen bond between the amide N atom and the O atom of the
      carbonyl group of the pyrone ring, forming an S(6) ring, and a weak Car-H?O
      hydrogen bond in which the carbonyl group of the amide acts as acceptor for the H
      atom of an ortho-C atom of the exocyclic phenyl ring, which results in another
      S(6) ring. The N-H?O intra-molecular hydrogen bond constrains the carboxamide
      moiety such that it is virtually coplanar with the chromone ring. 

PMID- 25995878
TI  - Crystal structure of bis-(2-amino-5-chloro-pyridinium) tetra-chlorido
      cobaltate(II).
AB  - The title salt, (C5H6ClN2)2[CoCl4], was synthesized by slow evaporation of an
      aqueous solution at room temperature. The asymmetric unit consists of two
      essentially planar (C5H6ClN2)(+) cations [maximum deviations = 0.010 (3) and
      0.014 (3) A] that are nearly perpendicular to each other [dihedral angle = 84.12
      (7) degrees ]. They are bonded through N-H?Cl hydrogen bonds to distorted
      [CoCl4](2-) tetra-hedra, leading to the formation of undulating layers parallel
      to (100). The structure is isotypic with the Zn analogue [Kefi et. al (2011).
      Acta Cryst. E67, m355-m356.]. 

PMID- 25995879
TI  - Crystal structure of disodium dicobalt(II) iron(III) tris-(orthophosphate) with
      an alluaudite-like structure.
AB  - The title compound, Na2Co2Fe(PO4)3, was synthesized by a solid-state reaction.
      This new stoichiometric phase crystallizes in an alluaudite-like structure. In
      this structure, all atoms are in general positions except for four atoms which
      are located at the special positions of the C2/c space group. One Co atom, one P
      and one Na atom are all located on Wyckoff position 4e (2), while the second Na
      atom is located on an inversion centre 4a (-1). The other Co and Fe atoms occupy
      a general position with a statistical distribution. The open framework results
      from [(Co,Fe)2O10] units of edge-sharing [(Co,Fe)O6] octa-hedra, which alternate
      with [CoO6] octa-hedra that form infinite chains running along the [10-1]
      direction. These chains are linked together through PO4 tetra-hedra by the
      sharing of vertices so as to build layers perpendicular to [010]. The three
      dimensional framework is accomplished by the stacking of these layers, leading to
      the formation of two types of tunnels parallel to [010] in which the Na(+)
      cations are located, each cation being surrounded by eight O atoms. 

PMID- 25995881
TI  - Crystal structure of [2-(tri-ethyl-ammonio)-eth-yl][(2,4,6-triiso-propyl-phen
      yl)sulfon-yl]amide tetra-hydrate.
AB  - The zwitterionic title compound, C23H42N2O2S.4H2O, crystallized as a tetrahydrate
      from a solution of N-[(2,4,6-triiso-propyl-phen-yl)sulfon-yl]aziridine in tri
      ethyl-amine, diethyl ether and pentane in the presence of moist air. It is formed
      by a nucleophillic ring-opening that is assumed to be reversible. The mol-ecular
      structure shows a major disorder of the triiso-propyl-phenyl group over two
      equally occupied locations. An inter-esting feature is the uncommon hydrate
      structure, exhibiting a tape-like motif which can be classified as a transition
      of the one-dimensional T4(2)6(2) motif into the two-dimensional L4(6)5(7)6(8)
      motif. 

PMID- 25995884
TI  - Crystal structure of (1,3-di-tert-butyl-eta(5)-cyclo-penta-dien-yl)tri-methyl
      hafnium(IV).
AB  - The mol-ecule of the title organometallic hafnium(IV) com-pound,
      [Hf(CH3)3(C13H21)] or [HfMe3(eta(5)-C5H3-1,3- (t) Bu2)], adopts the classical
      three-legged piano-stool geometry for mono-cyclo-penta-dienylhafnium(IV)
      derivatives with the three methyl groups bonded to the Hf(IV) atom at the legs.
      The C atoms of the two tert-butyl group bonded to the cyclo-penta-dienyl (Cp)
      ring are 0.132 (5) and 0.154 (6) A above the Cp least-squares plane. There are no
      significant inter-molecular inter-actions present between the mol-ecules in the
      crystal structure. 

PMID- 25995880
TI  - Crystal structure of trans-di-aqua-bis-(4-cyano-benzoato-kappaO)bis-(nicotinamide
      kappaN (1))cobalt(II).
AB  - In the title complex, [Co(C8H4NO2)2(C6H6N2O)2(H2O)2], the Co(II) atom is located
      on an inversion centre and is coordinated by two 4-cyano-benzoate (CNB) anions,
      two nicotinamide (NA) ligands and two water mol-ecules. The four O atoms in the
      equatorial plane form a slightly distorted square-planar arrangement, while the
      slightly distorted octa-hedral coordination sphere is completed by the two N
      atoms of the NA ligands in the axial positions. The dihedral angle between the
      carboxyl-ate group and the adjacent benzene ring is 22.11 (15) degrees , while
      the pyridine and benzene rings are oriented at a dihedral angle of 89.98 (5)
      degrees . In the crystal, inter-molecular N-H?O and O-H?O hydrogen bonds link the
      mol-ecules, enclosing R 2 (2)(8) and R 4 (4)(8) ring motifs, forming layers
      parallel to (100). The layers are linked via C-H?O and C-H?N hydrogen bonds,
      resulting in a three-dimensional network. A weak C-H?pi inter-action is also
      observed. 

PMID- 25995882
TI  - The crystal structure of 3-chloro-2-(4-methyl-phenyl)-2H-pyrazolo-[3,4
      b]quinoline.
AB  - In the mol-ecule of 3-chloro-2-(4-methyl-phen-yl)-2H-pyrazolo-[3,4-b]quinoline,
      C17H12ClN3, (I), the dihedral angle between the planes of the pyrazole ring and
      the methyl-ated phenyl ring is 54.25 (9) degrees . The bond distances in the
      fused tricyclic system provide evidence for 10-pi delocalization in the pyrazolo
      pyridine portion of the mol-ecule, with diene character in the fused carbocyclic
      ring. In the crystal, mol-ecules of (I) are linked by two independent C-H?N
      hydrogen bonds, forming sheets containing centrosymmetric R 2 (2)(16) and R 6
      (4)(28) rings, and these sheets are all linked together by pi-pi stacking inter
      actions with a ring-centroid separation of 3.5891 (9) A. 

PMID- 25995886
TI  - Crystal structure of (2-formyl-phenolato-kappa(2) O,O')oxido(2-{[(2-oxidoeth
      yl)imino]-meth-yl}phenolato-kappa(3) O,N,O')vanadium(V).
AB  - In the unsymmetrical title vanadyl complex, [V(C9H9NO2)(C7H5O2)O], one of the
      ligands (2-formyl-phenol) is disordered over two sets of sites, with an occupancy
      ratio of 0.55 (2):0.45 (2). The metal atom is hexa-coordinated, with a distorted
      octa-hedral geometry. The vanadyl O atom (which subtends the shortest V-O bond)
      occupies one of the apical positions and the remaining axial bond (the longest in
      the polyhedron) is provided by the (disordered) formyl O atoms. The basal plane
      is defined by the two phenoxide O atoms, the imino-alcoholic O and the imino N
      atom. The planes of the two benzene rings are almost perpendicular to each other,
      subtending an inter-planar angle of 84.1 (2) degrees  between the major parts.
      The crystal structure features weak C-H?O and C-H?pi inter-actions, forming a
      lateral arrangement of adjacent molecules. 

PMID- 25995885
TI  - Crystal structure of poly[di-MU-aqua-{5-[(1Z)-2-(4-chloro-phen-yl)-1-cyano
      ethenyl]-1,2,3,4-tetra-zol-1-ido-kappaN (1)}sodium].
AB  - In the title compound, [Na(C10H5ClN5)(H2O)2] n , infinite chains of [Na(H2O)2](+)
      cations having a diamond-shaped cross-section and running parallel to the b axis
      are formed. O-H?N hydrogen bonds to the anions generate layers parallel to (100)
      which have the chloro-benzene-cyano-ethenyl substituents protruding from both
      surfaces. The sodium ion makes a short contact of 2.4801 (13) A with the N atom
      of the tetra-zolide ring which is syn to the cyano N atom. 

PMID- 25995883
TI  - Crystal structure of Ba5In4Sb6.
AB  - The title compound, penta-barium tetra-indium hexa-anti-mony, was synthesized by
      an indium-flux reaction and its structure features layers composed of edge
      sharing In2Sb6 units. The voids between the In4Sb6 layers are filled by Ba(2+)
      cations, which are all surrounded by six Sb atoms and form bicapped octa-hedral
      or triangular prismatic coordination geometries. There are five barium ions in
      the asymmetric unit: one has no imposed crystallographic symmetry, two lie on
      mirror planes and two have mm2 point symmetry. The two In atoms and four Sb atoms
      in the asymmetric unit all lie on general crystallographic positions. 

PMID- 25995888
TI  - Crystal structure of catena-poly[[[aqua-bis-(1H-imidazole-kappaN (3))copper(II)]
      MU-3-({4-[(2-carboxyl-atoeth-yl)carbamo-yl]phen-yl}formamido)-propano-ato
      kappa(2) O:O'] dihydrate].
AB  - In the title polymeric complex, {[Cu(C14H14N2O6)(C3H4N2)2(H2O)].2H2O} n , the
      Cu(II) cation, located on a twofold rotation axis, is coordinated by one water
      mol-ecule and two imidazole mol-ecules as well as two symmetry-related 3-([4-[(2
      carboxyl-atoeth-yl)carbamo-yl]phen-yl]formamido)-propano-ate dianions (L (2-)) in
      an approximately square-pyramidal geometry. The coordinating water mol-ecule is
      located on a twofold rotation axis while the L (2-) anion sits about an inversion
      center. The L (2-) anions bridge the Cu(II) cations, forming polymeric chains
      propagating along the [101] direction. In the crystal, O-H?O, N-H?O hydrogen
      bonds and weak C-H?pi inter-action link the polymeric chains and the solvent
      water mol-ecules into a three-dimensional supra-molecular architecture. 

PMID- 25995887
TI  - Crystal structure of tricarbon-yltris(pyri-dine-kappaN)rhenium(I) tetra-fluorido
      borate.
AB  - In the title compound, [Re(C6H5N)3(CO)3]BF4, the Re(I) ion is six-coordinated by
      three pyridine N atoms and three carbonyl C atoms. In each case, the carbonyl C
      atom lies trans to a pyridine N atom. In the crystal, the ions are linked via C
      H?F hydrogen bonds and C-H?pi inter-actions, forming a three-dimensional
      framework. The F atoms of the BF4 anion are disordered over two positions and
      gave a final refined occupancy ratio of 0.705 (11):0.295 (11). 

PMID- 25995889
TI  - Crystal structure of 1-[2-(di-ethyl-aza-n-ium-yl)eth-yl]-3-methyl-imidazolium
      tetra-chlorido-cuprate(II).
AB  - The title compound, (C10H21N3)[CuCl4], is composed of one 1-[2-(di-ethyl-aza-nium
      yl)eth-yl]-3-methyl-imidazolium dication and a tetra-chlorido-cuprate(II)
      dianion. The anion adopts a distorted tetra-hedral geometry. Bifurcated
      interionic N-H?Cl hydrogen bonds and several C-H?Cl contacts are observed,
      leading to a layer-like arrangement of the components parallel to (100). 

PMID- 25995890
TI  - Crystal structure of di-chlorido-bis-(methyl isonicotinate-kappaN)copper(II).
AB  - In the title compound, [CuCl2(C7H7NO2)2], the square-planar-coordinated Cu(II)
      ion lies on a centre of symmetry and is bonded to two monodentate methyl
      isonicotinate ligands through their N atoms and by two chloride ligands. The mol
      ecules pack in a herringbone pattern. Perpendicular to [100] there are weak inter
      molecular C-H?Cl and C-H?O contacts. Along [100] there are infinite chains of
      edge-sharing octa-hedra linked through the chlorido ligands. 

PMID- 25995892
TI  - Crystal structure of tetra-kis-(MU3-2-{[1,1-bis-(hy-droxy-meth-yl)-2-oxidoeth
      yl]imino-meth-yl}phenolato)tetra-copper(II) ethanol monosolvate 2.5-hydrate.
AB  - The title compound, [Cu4(C11H13NO4)4].CH3CH2OH.2.5H2O, is an electronically
      neutral tetra-nuclear copper(II) complex with a cubane-like Cu4O4 core. The
      complete molecule has point group symmetry 2. The phenol hy-droxy group and one
      of the three alcohol hy-droxy groups of each 2-{[tris-(hy-droxy-meth-yl)meth
      yl]imino-meth-yl}phenol ligand are depro-ton-ated, while the secondary amine and
      the other two hy-droxy groups remain unchanged. The Cu(II) atoms in the Cu4O4
      core are connected by four MU3-O atoms from the deprotonated alcohol hy-droxy
      groups. Each of the penta-coordinated Cu(II) ions has an NO4 distorted square
      pyramidal environment through coordination to the tridentate Schiff base ligands.
      The Cu-N/O bond lengths span the range 1.902 (4)-1.955 (4) A, similar to values
      reported for related structures. There are O-H?O hydrogen-bond inter-actions
      between the complex molecules and the ethanol and water solvent molecules,
      leading to the formation of a three-dimensional network. The ethanol solvent
      molecule is disordered about a twofold rotation axis. One of the two independent
      water molecules is also located on this twofold rotation axis and shows half
      occupancy. 

PMID- 25995891
TI  - Hydro-thermal synthesis and crystal structure of a new lanthanum(III)
      coordination polymer with fumaric acid.
AB  - The title compound, poly[di-aqua-tris-(MU4-but-2-enedioato)(MU2-but-2-enedioic
      acid)dilanthanum(III)], [La2(C4H2O4)3(C4H4O4)(H2O)2] n , was synthesized by the
      reaction of lanthanum chloride penta-hydrate with fumaric acid under hydro
      thermal conditions. The asymmetric unit comprises an La(III) cation, one and a
      half fumarate dianions (L (2-)), one a half-mol-ecule of fumaric acid (H2 L) and
      one coordinated water mol-ecule. Each La(III) cation has the same nine-coordinate
      environment and is surrounded by eight O atoms from seven distinct fumarate
      moieties, including one proton-ated fumarate unit and one water mol-ecule in a
      distorted tricapped trigonal-prismatic environment. The LaO8(H2O) polyhedra
      centres are edge-shared through three carboxyl-ate bridges of the fumarate
      ligand, forming chains in three dimensions to construct the MOF. The crystal
      structure is stabilized by O-H?O hydrogen-bond inter-actions between the coordin
      ated water mol-ecule and the carboxyl-ate O atoms, and also between oxygen atoms
      of fumaric acid. 

PMID- 25995893
TI  - Crystal structure of catena-poly[bis-[MU3-2-(2-nitro-phen-yl)acetato-kappa(3)
      O:O:O']disilver(I)].
AB  - The title compound, [Ag2(C8H6NO4)2] n , is a silver complex of 2-(2-nitro-phen
      yl)acetic acid. The mol-ecules are not conventional crystallographic inversion
      dimers but consist of two independent ligands and two Ag(I) ions, each with a
      distorted T-shaped coordination environment. The dihedral angles between acetate
      groups and the benzene rings are 51.1 (2) and 57.9 (2) degrees . The nitro groups
      are oriented at dihedral angles of 23.6 (5) and 32.3 (3) degrees  with respect to
      the parent benzene rings. The dimers form polymeric chains along the a-axis
      direction. The Ag?Ag separation within a dimer is 2.8200 (5) and between symmetry
      related dimers is 3.6182 (5) A. The polymeric chains are inter-linked by C-H?O
      hydrogen-bond inter-actions. 

PMID- 25995894
TI  - Crystal structure of catena-poly[[[tetra-aqua-zinc(II)]-MU-1,4-bis-[4-(1H
      imidazol-1-yl)benzo-yl]piperazine] dinitrate monohydrate].
AB  - In the title polymeric complex, {[Zn(C24H22N6O2)(H2O)4](NO3)2.2H2O} n , the
      Zn(II) cation, located about a twofold rotation axis, is coordinated by two
      imidazole groups and four water mol-ecules in a distorted N2O4 octa-hedral
      geometry; among the four coordinate water mol-ecules, two are located on the same
      twofold rotation axis. The 1,4-bis-[4-(1H-imidazol-1-yl)benzo-yl]piperazine]
      ligand is centro-symmetric, with the centroid of the piperazine ring located on
      an inversion center, and bridges the Zn(II) cations, forming polymeric chains
      propagating along [201]. In the crystal, O-H?O and weak C-H?O hydrogen bonds link
      the polymeric chains, nitrate anions and solvent water mol-ecules into a three
      dimensional supra-molecular architecture. A short O?O contact of 2.823 (13) A is
      observed between neighboring nitrate anions. 

PMID- 25995895
TI  - Crystal structure of MU-peroxido-kappa(4) O (1),O (2):O (1'),O (2')-bis-[(nitrato
      kappaO)(2,2':6',2''-terpyridine-kappa(3) N,N',N'')dioxidouranium(VI)].
AB  - In the title dimeric complex, [{UO2(NO3)(C15H11N3)}2O2], a peroxide ion bridges
      the two uran-yl(VI) [O=U=O](2+) ions. The O-O bond length of the peroxide is
      1.485 (6) A and the mid-point of this bond is located at the inversion centre of
      the dimer. The U atom exhibits a distorted hexa-gonal-bipyramidal coordination
      geometry with two uran-yl(VI) O atoms occupying the axial positions and one O
      atom of the monodentate nitrate ion, both O atoms of the peroxide ion and the
      three N atoms of the chelating tridentate 2,2':6',2''-terpyridine (terpy) ligand
      in the equatorial positions. Two of the N atoms of the terpy ligand lie above and
      below the mean plane containing the equatorial ligand atoms and the U atom
      [deviations from the mean plane: maximum 0.500 (2), minimum -0.472 (2) and r.m.s.
      = 0.2910 A]. The dihedral angle between the terpy ligand and the mean plane is
      35.61 (7) degrees . The bond lengths around the U atom decrease in the order U-N
      > U-Onitrate > U-Operoxo > U=O. The dimeric complexes pack in a three-dimensional
      network held together by weak pi-pi inter-actions [centroid-centroid distance =
      3.659 (3) A] between pyridyl rings of the terpy ligands in neighbouring dimers,
      together with inter-molecular C-H?O and C-H?pi inter-actions. Weak intra
      molecular C-H?O inter-actions are also observed. 

PMID- 25995896
TI  - Crystal structure of (4-fluoro-phenyl-kappaC (1))iodido-(N,N,N',N'-tetra-methyl
      ethylenedi-amine-kappa(2) N,N')palladium(II).
AB  - In the title compound, [Pd(C6H4F)I(C6H16N2)], the Pd(II) atom is coordinated by
      two N atoms from the N,N,N',N'-tetra-methyl-ethylenedi-amine ligand, a C atom of
      the 4-fluoro-phenyl group and an iodide ligand in a distorted square-planar
      geometry, with an average deviation from the least-squares plane through the
      ligand donor atoms of 0.0159 (2) A. The angles about the Pd(II) atom range from
      83.35 (16) to 178.59 (11) degrees . In the crystal, weak C-H?F and C-H?I hydrogen
      bonds link the mol-ecules into sheets in the bc plane. 

PMID- 25995897
TI  - Crystal structure of bis-[4-(di-methyl-amino)-pyridine-kappaN (1)]bis-(methanol
      kappaO)bis-(thio-cyanato-kappaN)manganese(II).
AB  - The whole mol-ecule of the title compound, [Mn(NCS)2(CH3OH)2(C5H6N2)2], is
      generated by inversion symmetry. The Mn(II) ion, which is located on an inversion
      center, is coordinated by two 4-(di-methyl-amino)-pyridine ligands, two methanol
      ligands and two terminally N-bonded thio-cyanate anions, forming a slightly
      distorted octa-hedron. In the crystal, mol-ecules are linked by O-H?S hydrogen
      bonds, forming chains extending along the a-axis direction. 

PMID- 25995898
TI  - Crystal structure of ethyl 6-(2-fluoro-phen-yl)-4-hy-droxy-2-sulfanyl-idene-4-tri
      fluoro-meth-yl-1,3-diazinane-5-carboxyl-ate.
AB  - In the title compound, C14H14F4N2O3S, the central di-hydro-pyrimidine ring adopts
      a sofa conformation with the C atom bearing the 2-fluoro-benzene ring displaced
      by 0.596 (3) A from the other five atoms. The 2-fluoro-benzene ring is positioned
      axially and bis-ects the pyrimidine ring with a dihedral angle of 70.92 (8)
      degrees . The mol-ecular conformation is stabilized by an intra-molecular O-H?O
      hydrogen bond, generating an S(6) ring. The crystal structure features C-H?F, N
      H?S and N-H?O hydrogen bonds, which link the mol-ecules into a three-dimensional
      network. 

PMID- 25995900
TI  - Crystal structure of 2-(1-methyl-eth-yl)-1,3-thia-zolo[4,5-b]pyridine.
AB  - In the title mol-ecule, C9H10N2S, one of the methyl groups is almost co-planar
      with the thia-zolo-pyridine rings with a deviation of 0.311 (3) A from the least
      squares plane of the thia-zolo-pyridine group. In the crystal, weak C-H?N
      hydrogen-bonding inter-actions lead to the formation of chains along [011]. 

PMID- 25995899
TI  - Crystal structure of quinolinium 2-carboxy-6-nitro-benzoate monohydrate.
AB  - In the anion of the title hydrated mol-ecular salt, C9H8N(+).C8H4NO6 (-).H2O, the
      protonated carboxyl and nitro groups makes dihedral angles of 27.56 (5) and 6.86
      (8) degrees , respectively, with the attached benzene ring, whereas the
      deprotonated carb-oxy group is almost orthogonal to it with a dihedral angle of
      80.21 (1) degrees . In the crystal, the components are linked by O-H?O and N-H?O
      hydrogen bonds, generating [001] chains. The packing is consolidated by weak C
      H?N and C-H?O inter-actions as well as aromatic pi-pi stacking [centroid-to
      centroid distances: 3.7023 (8) & 3.6590 (9)A] inter-actions, resulting in a three
      dimensional network. 

PMID- 25995901
TI  - Crystal structure of methyl 1-methyl-2-oxo-spiro-[indoline-3,2'-oxirane]-3'
      carboxyl-ate.
AB  - In the title compound, C12H11NO4, the dihedral angle between the indole ring
      system (r.m.s. deviation = 0.019 A) and the oxirane ring is 88.8 (2) degrees .
      The oxirane O atom and the bridging ester O atom are in an approximate syn
      conformation [O-C-C-O = -25.4 (3) degrees ] In the crystal, inversion dimers
      linked by pair of C-H?O hydrogen bonds generate R 2 (2)(8) loops, where the C-H
      donor group forms part of the oxirane ring. A second C-H?O inter-action arising
      from one of the C-H groups of the benzene ring links the dimers into [001] double
      chains. 

PMID- 25995902
TI  - Crystal structure of (2-methyl-4-phenyl-4H-benzo[4,5]thia-zolo[3,2-a]pyrimidin-3
      yl)(phen-yl)methanone.
AB  - In the title compound, C24H18N2OS, the pyrimidine ring has a flat envelope
      conformation with the methine C atom as the flap. The attached phenyl and benzoyl
      rings are inclined to the mean plane of the pyrimidine ring by 84.87 (8) and
      75.33 (9) degrees , respectively. The benzo-thia-zolo group is planar (r.m.s.
      deviation = 0.009 A) and inclined to the mean plane of the pyrimidine ring by
      3.27 (6) degrees . In the crystal, mol-ecules are linked by pairs of C-H?N
      hydrogen bonds, forming inversion dimers. 

PMID- 25995903
TI  - Crystal structure of 5,5'-di-bromo-3,3'-di-tert-butyl-6,6'-di-methyl-biphenyl
      2,2'-diol.
AB  - The whole mol-ecule of the title compound, C22H28Br2O2, is generated by twofold
      rotation symmetry. The dihedral angle of the biphenyl moiety is 85.05 (11)
      degrees . The hy-droxy groups show intra-molecular O-H?pi inter-actions without
      any other hydrogen-bond acceptors. In the crystal, there are no other significant
      inter-molecular inter-actions present. 

PMID- 25995904
TI  - Crystal structure of [1-(3-chloro-phen-yl)-5-hy-droxy-3-methyl-1H-pyrazol-4-yl](p
      tol-yl)methanone.
AB  - In the title compound C18H15ClN2O2, the dihedral angles between the central
      pyrazole ring and the pendant chloro-benzene and p-tolyl rings are 17.68 (10) and
      51.26 (12) degrees , respectively. An intra-molecular O-H?O hydrogen bond is
      observed, which closes an S(6) ring. 

PMID- 25995905
TI  - Crystal structure of methyl 2-hy-droxy-5-[(4-oxo-4,5-di-hydro-1,3-thia-zol-2
      yl)amino]benzoate.
AB  - The title compound, C11H10N2O4S, crystallized with two independent mol-ecules (A
      and B) in the asymmetric unit. They differ primarily in the rotational
      orientation of the five-membered heterocyclic ring. In mol-ecule A this ring is
      inclined to the benzene ring by 48.17 (8) degrees , while in mol-ecule B the same
      dihedral angle is 23.07 (8) degrees . In each mol-ecule there is an intra
      molecular O-H?O hydrogen bond involving the adjacent hydroxyl group and the ester
      carbonyl O atom. In the crystal, the A mol-ecules are linked via pairs of N-H?N
      hydrogen bonds, forming inversion dimers. These dimers are linked to the B mol
      ecules via N-H..O, C-H?O and C-H?S hydrogen bonds forming corrugated sheets lying
      parallel to (102). 

PMID- 25995906
TI  - Crystal structure of (1S,3R,8R,9S,10R)-10-bromo-methyl-2,2-di-chloro-9,10-ep-oxy
      3,7,7-tri-methyl-tri-cyclo-[6.4.0.0(1,3)]dodeca-ne.
AB  - The title compound, C16H23BrCl2O, was synthesized in three steps from beta
      himachalene (3,5,5,9-tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo
      heptene), which was isolated from the essential oil of the Atlas cedar (cedrus
      atlantica). The mol-ecule is built up from two fused six- and seven-membered
      rings, each linked to a three-membered ring. The six-membered ring has a screw
      boat conformation, whereas the seven-membered ring displays a twist-boat
      conformation. The absolute structure was established unambiguously from anomalous
      dispersion effects. 

PMID- 25995907
TI  - Crystal structure of tetra-butyl-ammonium bromide-1,2-di-iodo-3,4,5,6-tetra
      fluoro-benzene-di-chloro-methane (2/2/1).
AB  - The crystallization of a 1:1 molar solution of 1,2-di-iodo-3,4,5,6-tetra-fluoro
      benzene (o-DITFB) and tetra-butyl-ammonium bromide (n-Bu4NBr) from di-chloro
      methane yielded pure white crystals of a halogen-bonded compound, C16H36N(+).Br(
      ).C6F4I2.0.5CH2Cl2 or [(n-Bu4NBr)(o-DITFB)].0.5CH2Cl2. The compound may be
      described as a quaternary system and may be classified as a salt-cocrystal
      solvate. The asymmetric unit contains one mol-ecule of solvent, two o-DITFB mol
      ecules, two cations (n-Bu4N(+)) and two crystallographically distinct bromide
      ions [thetaI ? Br- ? I = 144.18 (1) and 135.35 (1) degrees ]. The bromide ion is
      a bidentate halogen-bond acceptor which inter-acts with two covalently bonded
      iodines (i.e. halogen-bond donors), resulting in a one-dimensional polymeric
      zigzag chain network approximately along the a axis. The observed short contacts
      and angles are characteristic of the non-covalent inter-action [d C-I?Br = 3.1593
      (4)-3.2590 (5) A; thetaC-I?Br = 174.89 (7) and 178.16 (7) degrees ]. It is noted
      that iodine acts as both a halogen-bond donor and a weak CH hydrogen-bond
      acceptor, while the bromide ions act as acceptors for weak CH hydrogen bonds and
      halogen bonds. 

PMID- 25995908
TI  - Crystal structure of 2-{(E)-[(2-hy-droxy-phen-yl)iminium-yl]meth-yl}-4-methyl
      phenolate.
AB  - The title compound, C14H13NO2, exists as a zwitterion in the solid state, with
      the H atom of the phenol group transferred to the imine N atom. The dihedral
      angle between the planes of the benzene rings is 10.13 (9) degrees . Intra
      molecular N-H?O hydrogen bond generate S(6) and S(5) loops. In the crystal, mol
      ecules are connected by O-H?O hydrogen bonds, generating C(9) chains propagating
      in the [010] direction. 

PMID- 25995909
TI  - Crystal structure of beta-d,l-psicose.
AB  - The title compound, C6H12O6, a C-3 position epimer of fructose, was crystallized
      from an aqueous solution of equimolar mixture of d- and l-psicose (1,3,4,5,6
      penta-hydroxy-hexan-2-one, ribo-2-hexulose, allulose), and it was confirmed that
      d-psicose (or l-psicose) formed beta-pyran-ose with a (2) C 5 (or (5) C 2)
      conformation. In the crystal, an O-H?O hydrogen bond between the hy-droxy groups
      at the C-3 and C-2 positions connects homochiral mol-ecules into a column along
      the b axis. The columns are linked by other O-H?O hydrogen bonds between d- and l
      psicose mol-ecules, forming a three-dimensional network. An intra-molecular O-H?O
      hydrogen bond is also observed. The cell volume of racemic beta-d,l-psicose
      [763.21 (6) A(3)] is almost the same as that of chiral beta-d-psicose [753.06
      A(3)]. 

PMID- 25995910
TI  - Crystal structure of ethyl 2-{4-[(5-chloro-1-benzo-furan-2-yl)meth-yl]-3-methyl-6
      oxo-1,6-di-hydro-pyridazin-1-yl}acetate.
AB  - In the title compound, C18H17ClN2O4, the dihedral angle between the benzofuran
      ring system [maximum deviation 0.014 (2) A] and the oxopyradizine ring is 73.33
      (8) degrees . The structure is characterized by disorder of the ethyl group,
      which is split into two parts, with a major component of 0.57 (3), and the
      acetate carbonyl O atom, which is statistically disordered. In the crystal, the
      molecules are linked by C-H?O inter-actions, forming a three-dimensional network.

PMID- 25995911
TI  - Crystal structure of 11-(2,3-di-meth-oxy-phen-yl)-14-methyl-12-oxa-8,14-di-aza
      tetra-cyclo-[8.3.3.0(1,10).0(2,7)]hexa-deca-2(7),3,5-triene-9,13-dione.
AB  - The title compound, C22H22N2O5, contains two conformationally similar mol-ecules
      (A and B) in its the asymmetric unit (r.m.s. overlay fit for the 29 non-H atoms =
      0.194 A). In each mol-ecule, the lactone ring has an envelope conformation with
      the spiro C atom as the flap. In the crystal, A+A and B+B inversion dimers linked
      by pairs of N-H?O hydrgen bonds occur; in both cases, R 2 (2)(8) loops are
      generated. A weak C-H?O inter-action is also observed, which links the dimers
      into [010] chains. 

PMID- 25995912
TI  - Crystal structure of febuxostat-acetic acid (1/1).
AB  - The asymmetric unit of the title compound [systematic name: 2-(3-cyano-4-iso
      butyl-oxyphen-yl)-4-methyl-thia-zole-5-carb-oxy-lic acid-acetic acid (1/1)],
      C16H16N2O3S.CH3COOH, contains a febuxostat mol-ecule and an acetic acid mol
      ecule. In the febuxostat mol-ecule, the thia-zole ring is nearly coplanar with
      the benzene ring [dihedral angle = 3.24 (2) degrees ]. In the crystal, the
      febuxostat and acetic acid mol-ecules are linked by O-H?O, O-H?N hydrogen bonds
      and weak C-H?O hydrogen bonds, forming supra-molecular chains propagating along
      the b-axis direction. pi-pi stacking is observed between nearly parallel thia
      zole and benzene rings of adjacent mol-ecules; the centroid-to-centroid distances
      are 3.8064 (17) and 3.9296 (17) A. 

PMID- 25995913
TI  - Crystal stucture of methyl 2-({[2-(meth-oxy-carbon-yl)phen-yl]carbamo-yl}amino)
      benzoate.
AB  - In the title compound, C17H16N2O5, the dihedral angles between the central urea
      [N-C(=O)-N] fragment and its attached benzene rings are 20.20 (14) and 24.24 (13)
      degrees ; the dihedral angle between the aromatic rings is 42.1 (1) degrees . The
      mol-ecular conformation is consolidated by two intra-molecular N-H?O hydrogen
      bonds, which both generate S(6) rings. In the crystal, inversion dimers linked by
      pairs of C-H?O inter-actions generate R 2 (2)(14) loops. The dimers are linked by
      further C-H?O inter-actions into (011) sheets. 

PMID- 25995914
TI  - Crystal structure of 1-[2-(2,6-di-chloro-phen-yl)-4,5-diphenyl-1H-imidazol-1
      yl]propan-2-ol.
AB  - The central imidazole ring of the title compound, C24H20Cl2N2O, is twisted with
      respect to with the planes of the 2,6-di-chloro-benzene and two phenyl rings,
      making dihedral angles of 74.06 (18), 28.52 (17) and 67.65 (18) degrees ,
      respectively. The phenyl ring not adjacent to the N-bonded 2-hy-droxy-propyl
      group shows the greatest twist, presumably to minimize steric inter-actions. In
      the crystal, mol-ecules are linked by O-H?N and C-H?O hydrogen-bond contacts into
      chains along the a-axis direction. The series of parallel chains form a two
      dimensional sheet approximately parallel to the bc diagonal. In addition, C-H?pi
      inter-actions are observed between the sheets. The atoms of the 2-hy-droxy-propyl
      group and the N atom of the 1H-imidazole ring to which it is bonded are
      disordered over two sets of sites, with an occupancy ratio of 0.722 (5):0.278
      (5). The structure was refined as an inversion twin. 

PMID- 25995915
TI  - Crystal structure of 2-(1H-imidazol-4-yl)ethanaminium chloride.
AB  - The title mol-ecular salt, C5H10N3 (+).Cl(-), was obtained as by-product in the
      attempted synthesis of a histamine derivative. The terminal amino group of the
      starting material is protonated. The Cimidazole-C-C-N(H3)(+) group in the cation
      is in an anti conformation with a torsion angle of 176.22 (10) degrees . In the
      crystal, cations and anions are linked via N-H?N and N-H-Cl hydrogen bonds,
      forming a two-dimensional network parallel to (10-1). A single weak C-H?Cl
      hydrogen bond completes a three-dimensional network. 

PMID- 25995916
TI  - Crystal structure of 1-[(Z)-2-phenyl-hydrazin-1-yl-idene]naphthalen-2(1H)-one.
AB  - In the title compound, C16H12N2O, the dihedral angle between the planes of the
      benzene ring and naphthalenone ring system is 1.89 (8) degrees ; an intra
      molecular N-H?O hydrogen bond occurs between the imino group and the carbonyl
      group. In the crystal, mol-ecules are linked by weak C-H?pi inter-actions into
      supra-molecular chains propagating along the [01-1] direction. 

PMID- 25995917
TI  - Crystal structure of 5,11-di-hydro-pyrido[2,3-b][1,4]benzodiazepin-6-one.
AB  - The title compound, C12H9N3O, is an inter-mediate in the synthesis of the
      muscarinic M2 receptor antagonist AFDX-384. The seven-membered ring adopts a boat
      conformation and the dihedral angle between the planes of the aromatic rings is
      41.51 (9) degrees . In the crystal, mol-ecules are linked into [001] chains of
      alternating inversion dimers formed by pairs of N-H?O hydrogen bonds and pairs of
      N-H?N hydrogen bonds. In both cases, R 2 (2)(8) loops are generated. 

PMID- 25995918
TI  - Crystal structure of ethyl 4-(2,4-di-chloro-phen-yl)-2-methyl-4H-benzo[4,5]thia
      zolo[3,2-a]pyrimidine-3-carboxyl-ate.
AB  - In the title compound, C20H16Cl2N2O2S, the pyrimidine ring has a screw-boat
      conformation. The attached di-chloro-phenyl ring is twisted at an angle of 89.29
      (13) degrees  with respect to the pyrimidine ring mean plane. The benzo-thia-zole
      group is approximately planar (r.m.s. deviation = 0.008 A) and inclined to the
      pyrimidine ring mean plane by 3.04 (10) degrees . The carboxyl-ate group assumes
      an extended conformation with respect to the pyrimidine ring, which can be seen
      from the O=C-O-C torsion angle of 3.2 (4)  degrees . In the crystal, mol-ecules
      are linked via C-H?O and C-H?N hydrogen bonds, forming slabs lying parallel to
      (100). 

PMID- 25995919
TI  - Crystal structure of (2S)-3-methyl-2-[(naphthalen-1-ylsulfon-yl)amino]-butanoic
      acid.
AB  - The title compound, C15H17NO4S, was synthesized from l-valine and naphthalene-1
      sulfonyl chloride. The hydrogen-bonded carb-oxy-lic acid groups form a catemer
      C(4) motif extending along [100]. The catemer structure is reinforced by a rather
      long N-H?O hydrogen bond, between the sulfamide N-H group and a carb-oxy-lic acid
      O atom [H?O = 2.52 (2) A], and a C-H?O hydrogen bond. 

PMID- 25995920
TI  - Crystal structure of (E)-1-(4-tert-butyl-phen-yl)-2-(4-iodo-phen-yl)ethene.
AB  - The title compound, C18H19I, crystallized with two independent mol-ecules (A and
      B) in the asymmetric unit. Both mol-ecules have an E conformation about the
      bridging C=C bond. They differ in the orientation of the two benzene rings; the
      dihedral angle being 12.3 (5) degrees  in mol-ecule A, but only 1.0 (6) degrees 
      in mol-ecule B. In the crystal, the individual mol-ecules are linked by C-I?pi
      inter-actions forming zigzag A and zigzag B chains propagating along [001]. The
      structure was refined as an inversion twin [Flack parameter = 0.48 (2)]. 

PMID- 25995921
TI  - Crystal structure of 1-nitro-4-(tri-methyl-silylethyn-yl)naphthalene.
AB  - In the title compound, C15H15NO2Si, the dihedral angle between the nitro group
      and the mean plane of the naphthalene system is 22.04 (11) degrees . In the
      crystal, pi-pi inter-actions generate supra-molecular chains propagating along
      the a-axis direction; the centroid-to-centroid distances range from 3.5590 (12)
      to 3.8535 (12) A. 

PMID- 25995922
TI  - Crystal structure of 4-hy-droxy-3-meth-oxy-benzaldehyde 4-methyl-thio-semi
      carbazone methanol monosolvate.
AB  - In the title solvate, C15H15N3O2S.CH3OH, the thio-semicarbazone mol-ecule is
      approximately planar; the maximum deviation from the mean plane is 0.4659 (14) A
      and the dihedral angle between the aromatic rings is 9.83 (8) degrees . This
      conformation is supported by an intra-molecular N-H?N hydrogen bond. In the
      crystal, the thio-semicarbazone mol-ecules are linked into dimers by pairs of N
      H?S hydrogen bonds, thereby generating R 2 (2)(8) loops. The methanol solvent mol
      ecule bonds to the thio-semicarbazone mol-ecule through a bifurcated O-H?(O,O)
      hydrogen bond and also accepts an O-H?O link from the thio-semicarbazone mol
      ecule. Together, these links generate a three-dimensional network. 

PMID- 25995923
TI  - Crystal structure of 2-chloro-N-(3-fluoro-phen-yl)acetamide.
AB  - In the title compound, C8H7ClFNO, the F atom is disordred over the meta positions
      of the benzene ring in a 0.574 (4):0.426 (4) ratio and the Cl atom is syn to the
      O atom [O-C-C-Cl = 5.6 (3) degrees ]. A short intra-molecular C-H?O contact
      occurs. In the crystal, mol-ecules are linked into amide C(4) chains propagating
      in [101] by N-H?O hydrogen bonds. 

PMID- 25995924
TI  - Crystal structure of (E)-pent-2-enoic acid.
AB  - The mol-ecule of the title compound, C5H8O2, a low-melting alpha,beta-unsaturated
      carb-oxy-lic acid, is essentially planar [maximum displacement = 0.0239 (13) A].
      In the crystal, mol-ecules are linked into centrosymmetric dimers via pairs of O
      H?O hydrogen bonds. 

PMID- 25995925
TI  - Crystal structure of 4-formyl-pyridine semicarbazone hemihydrate.
AB  - The mol-ecule of the title compound C7H8N4O.0.5H2O, alternatively called (E)-1
      (pyridin-4-yl-methyl-ene)semi-carb-azide hemihydrate, is in the E conformation
      and is almost planar; the r.m.s. deviation of the positions of the atoms of the
      pyridine ring from the best-fit plane is 0.0039 A. The C, N and O atoms of the
      rest of the mol-ecule sits close on this plane with a largest deviation of 0.115
      (4) A for the O atom of the semicarbazone moiety. There is an intra-molecular N
      H?N hydrogen bond. In the crystal, mol-ecules are linked into an infinite three
      dimensional network by classical N-H?Os (s = semicarbazone) and Ow-H?N (w =
      water) hydrogen bonds. 

PMID- 25995926
TI  - Crystal structure of tetra-ethyl-ammonium chloride 3,4,5,6-tetra-fluoro-1,2-di
      iodo-benzene.
AB  - Equimolar qu-anti-ties of tetra-ethyl-ammonium chloride (Et4NCl) and 3,4,5,6
      tetra-fluoro-1,2-di-iodo-benzene (o-DITFB or o-C6F4I2) have been co-crystallized
      in a solution of di-chloro-methane yielding a pure halogen-bonded compound,
      3,4,5,6-tetra-fluoro-1,2-di-iodo-benzene-tetra-ethyl ammonium chloride (2/1),
      Et4N(+).Cl(-).2C6F4I2, in the form of translucent needles. [(Et4NCl)(o-C6F4I2)2]
      packs in the C2/c space group. The asymmetric unit includes one mol-ecule of
      DITFB, one Et4N(+) cation located on a twofold rotation axis, and one chloride
      anion also located on a twofold rotation symmetry axis. This compound has an
      inter-esting halogen-bonding environment surrounding the halide. Here, the
      chloride anion acts as a tetra-dentate halogen bond acceptor and forms a
      distorted square-pyramidal geometry, with I?Cl(-)?I angles of 80.891 (6) and
      78.811 (11) degrees , where two crystallographically distinct iodine atoms form
      halogen bonds with the chloride anion. Resulting from that square-pyramidal
      geometry are short contacts between some of the adjacent F atoms. Along the b
      axis, the halogen-bonding inter-action results in a polymeric network, producing
      a sheet in which the two closest chloride ions are 7.8931 (6) A apart. The
      Et4N(+) cation alternates in columns with the halide ion. The expected short
      contacts (shorter than the sum of their van der Waals radii) are observed for the
      halogen bonds [3.2191 (2) and 3.2968 (2) A], as well as almost linear angles
      [170.953 (6) and 173.529 (6) degrees ]. 

PMID- 25995927
TI  - Crystal structure of ({4-[(4-bromo-phen-yl)ethyn-yl]-3,5-di-ethyl-phen-yl}ethyn
      yl)triiso-propyl-silane.
AB  - The title compound, C29H37BrSi, was synthesized by the Sonogashira coupling of
      [(3,5-diethyl-4-ethynylphen-yl)ethyn-yl]triiso-propyl-silane with 4-bromo-1-iodo
      benzene. In the structure, the two phenyl rings are nearly parallel to each other
      with a dihedral angle of 4.27 (4) degrees . In the crystal, pi-pi inter-actions
      between the terminal and central phenyl rings of adjacent mol-ecules link them in
      the a-axis direction [perpendicular distance = 3.5135 (14); centroid-centroid
      distance = 3.7393 (11) A]. In addition, there are weak C-H?pi inter-actions
      between the isopropyl H atoms and the phenyl rings of adjacent mol-ecules. 

PMID- 25995928
TI  - Crystal structure of (E)-hex-2-enoic acid.
AB  - The crystal structure of the title compound, C6H10O2, an alpha,beta-unsaturated
      carb-oxy-lic acid, displays carb-oxy-lic acid inversion dimers linked by pairs of
      O-H?O hydrogen bonds. The packing is characterized by layers of acid dimers. All
      the non-H atoms of the (E)-hex-2-enoic acid mol-ecule lie almost in the same
      plane (r.m.s. deviation for the non-H atoms = 0.018 A). 

PMID- 25995929
TI  - Crystal structure of 2-(5-bromo-2-hy-droxy-benzyl-idene)-2,3-di-hydro-1H-indene
      1,3-dione.
AB  - The title mol-ecule, C16H9BrO3, deviates slightly from planarity. The benzene
      ring makes a dihedral angle of 1.02 (9) degrees  with the plane defined by the
      five-membered ring of the indandione moiety. The latter exhibits a minute twist
      indicated by the dihedral angle of 0.47 (9) degrees  between the planes of the
      five- and six-membered rings. An intra-molecular C-H?O hydrogen bond between the
      attached benzene ring with one of the indandione carbonyl O atoms stabilizes the
      mol-ecular conformation. In the crystal, the mol-ecules form dimers across
      centres of inversion via pairwise O-H?O hydrogen bonds. The dimers form stacks
      running parallel to [010] and inter-act through pi-pi inter-actions between the
      five-membered ring of one mol-ecule and the six-membered rings of the indandione
      moiety of an adjacent mol-ecule [centroid-to-centroid distance = 3.5454 (10) A]. 

PMID- 25995930
TI  - Crystal structure of 4-bromo-phenyl-2-oxo-2H-chromene-3-carboxyl-ate.
AB  - In the title compound, C16H9BrO4, the coumarin ring system is approximately
      planar, with an r.m.s deviation of the ten fitted non-H atoms of 0.031 A, and
      forms a dihedral angle of 25.85 (10) degrees  with the bromo-benzene ring. The
      carbonyl atoms are syn. In the crystal, mol-ecules are connected along [001] via
      C-H?O inter-actions, forming C(6) chains. Neighbouring C(6) chains are connected
      via several pi-pi inter-actions [range of centroid-centroid distances = 3.7254
      (15)-3.7716 (16) A], leading to sheets propagating in the bc plane. 

PMID- 25995931
TI  - Cystal structre of 5-hy-droxy-2-nitro-benzaldehyde.
AB  - In the title compound, C7H5NO4, the nitro group and the aldehyde group are
      inclined to the benzene ring by 16.6 (3) and 15.6 (3) degrees , respectively. In
      the crystal, mol-ecules are linked via O-H?O hydrogen bonds, forming chains along
      [100]. The chains are linked by C-H?O hydrogen bonds, forming a three-dimensional
      structure. 

PMID- 25995932
TI  - Crystal structure of bis-(4-meth-oxy-phenyl) malonate.
AB  - The complete mol-ecule of the title compound, C17H16O6, is generated by
      crystallographic twofold symmetry, with the central methyl-ene C atom lying on
      the rotation axis. The carbonyl O atom is disordered over two adjacent positions
      in a 0.63 (3):0.37 (3) ratio and the dihedral angle between the benzene rings in
      the two halves of the mol-ecule is 79.31 (12) degrees . In the crystal, mol
      ecules are connected by C-H?O hydrogen bonds, generating (110) sheets. Very weak
      intra-sheet C-H?pi inter-actions are also observed. 

PMID- 25995933
TI  - Crystal structure of 3-(4-meth-oxy-phen-yl)-2,3-di-hydro-1H-naphtho-[2,1-b]pyran
      1-one.
AB  - In the title compound, C20H16O3, the hydro-pyran ring adopts a distorted half
      chair conformation with the methine C atom and the ring O atom displaced by 
      0.554 (2) and 0.158 (1) A, respectively, from the plane of the other four atoms
      (r.m.s. deviation = 0.020 A). Its mean plane (all atoms) is inclined to the
      naphthalene ring system at a dihedral angle of 11.67 (1) degrees . The dihedral
      angle between the napthalene ring system and the phenyl ring is 71.84 (1) degrees
      . In the crystal, no diectional inter-actions beyond van der Waals contacts could
      be identified. 

PMID- 25995934
TI  - Crystal structure of 2-(11-oxo-10H,11H-indeno-[1,2-b]chromen-10-yl)-2,3-di-hydro
      1H-indene-1,3-dione.
AB  - In the title mol-ecule, C25H14O4, the fused-ring system consisting of four rings
      is approximately planar, with a dihedral angle of 9.62 (5) degrees  between the
      planes of the indene ring system and the benzene ring. The di-hydro-indene-1,3
      dione unit makes a dihedral angle of 63.50 (2) degrees  with the mean plane of
      the fused-ring system. A weak C-H?O inter-action organizes the mol-ecules into a
      helical chain along the b axis. In addition, there is a pi-pi stacking inter
      action between the five-membered rings of adjacent fused-ring systems, with a
      centroid-centroid distance of 3.666 (1) A. 

PMID- 25995935
TI  - Crystal structure of 4-(2-azido-phen-yl)-5-benzoyl-2-(1H-indol-3-yl)-1H-pyrrole-3
      carbo-nitrile.
AB  - In the title compound, C26H16N6O, the dihedral angles between the central pyrrole
      ring and the pendant indole ring system (r.m.s. deviation = 0.027 A) and the
      azide-bearing benzene ring are 37.56 (8) and 51.62 (11) degrees , respectively.
      The azide group is almost coplanar with its attached benzene ring [C-C-N-N = 3.8
      (3) degrees ]. The benzoyl benzene ring is disordered over two orientations
      twisted with respect to each other by 9.29 (8) degrees  in a 0.514 (2):0.486 (2)
      ratio. In the crystal, inversion dimers linked by pairs of Np-H?O (p = pyrrole)
      hydrogen bonds generate R 2 (2)(10) loops. A second inversion dimer arises from a
      pair of Ni-H?Nc (i = indole and c = cyanide) hydrogen bonds, which generates an R
      2 (2)(16) loop. Together, the hydrogen bonds lead to [011] chains in the crystal.

PMID- 25995936
TI  - Crystal structure of 3-(2,5-di-meth-oxy-phen-yl)propionic acid.
AB  - In the crystal of the title compound, C11H14O4, the aromatic ring is almost
      coplanar with the 2-position meth-oxy group with which it subtends a dihedral of
      0.54 (2) degrees , while the 5-position meth-oxy group makes a corresponding
      dihedral angle of just 5.30 (2) degrees . The angle between the mean planes of
      the aromatic ring and the propionic acid group is 78.56 (2) degrees . The fully
      extended propionic side chain is in a trans configuration with a C-C-C-C torsion
      angle of -172.25 (7) degrees . In the crystal, hydrogen bonding is limited to
      dimer formation via R 2 (2)(8) rings. The hydrogen-bonded dimers are stacked
      along the b axis. The average planes of the two benzene rings in a dimer are
      parallel to each other, but at an offset of 4.31 (2) A. Within neighbouring
      dimers along the [101] direction, the average mol-ecular benzene planes are
      almost perpendicular to each other, with a dihedral angle of 85.33 (2) degrees . 

PMID- 25995937
TI  - Crystal structure of bis-(3,3-dimethyl-2-oxobut-yl)di-phenyl-phospho-nium bromide
      chloro-form monosolvate.
AB  - In the title salt solvate, C24H32O2P(+).Br(-).CHCl3, the P atom has a distorted
      tetra-hedral geometry, and the planes of the phenyl rings form a dihedral angle
      of 71.86 (14) degrees  with one another. The bromide anion is disordered and was
      modelled over three positions (occupancy ratio 0.50:0.35:0.15). The crystal also
      contains one disordered chloro-form solvent mol-ecule that was modeled over three
      positions (occupancy ratio 0.50:0.35:0.15). Weak inter-molecular inter-actions (C
      H?Br and C-H?O) exist between the complex cation and the bromide anion fragments.
      The resulting supramolecular structure is an oval-shaped arrangement of
      phosphonium salt molecules that surround the disordered bromide anion. 

PMID- 25995938
TI  - Crystal structure of ethyl 2-(3,5-di-fluoro-phen-yl)quinoline-4-carboxyl-ate.
AB  - In the title compound, C18H13F2NO2, the two rings of the quinoline system are
      fused almost coaxially, with a dihedral angle between their planes of 2.28 (8)
      degrees . The plane of the attached benzene ring is inclined to the plane of the
      quinoline system by 7.65 (7) degrees . The carboxyl-ate group attached to the
      quinoline system is in an anti-periplanar conformation. There is a short intra
      molecular C-H?O contact involving the carbonyl group. In the crystal, mol-ecules
      are linked via C-H?O hydrogen bonds, forming chains lying in the (1-10) plane. 

PMID- 25995939
TI  - Crystal structure of anagyrine perchlorate.
AB  - The title mol-ecular salt, C15H21N2O(+).ClO4 (-), crystallizes with four cations
      (A, B, C and D) and four anions in the chiral unit cell (space group P21). The
      alkaloid was isolated from the aerial parts of Genista Hispanica collected in the
      Samarkand region of Uzbekistan. Each cation is protonated at the N atom that
      bridges the alkaloid rings C and D. In each cation, ring A is almost planar and
      ring B adops a sofa conformation with the methyl-ene group bridging to the C ring
      as the flap. Rings C and D adopt chair conformations with a cis ring junction in
      all four cations. In the crystal, A+B and C+D dimeric pairs linked by pairs of N
      H?O hydrogen bonds are observed, which generate R 2 (2)(16) loops in each case.
      The dimers are consolidated by weak aromatic pi-pi stacking inter-actions between
      the A rings [centroid-centroid distances = 3.913 (3) and 3.915 (3) A]. 

PMID- 25995940
TI  - Crystal structure of 9-butyl-6-[2-(pyridin-4-yl)ethen-yl]carbazol-3-amine.
AB  - The asymmetric unit of the title compound, C23H23N3, consists of two mol-ecules,
      A and B, with different conformations. In mol-ecule A, the dihedral angle between
      the carbazole ring system (r.m.s. deviation = 0.028 A) and the pyridine ring is
      20.28 (9) degrees  and the N-C-C-C torsion angle of the butyl side chain is -63.4
      (3) degrees . The equivalent data for mol-ecule B are 0.065 A, 48.28 (11) degrees
      and 61.0 (3) degrees , respectively. In the crystal, the components are
      connected by weak N-H?N hydrogen bonds, generating [030] C(14) chains of
      alternating A and B mol-ecules. 

PMID- 25995941
TI  - Crystal structure of 4'-bromo-2,3,5,6-tetra-fluoro-biphenyl-4-carbo-nitrile.
AB  - The title compound, C13H4BrF4N, synthesized from 1,4'-bromo-iodo-benzene and 4
      bromo-2,3,5,6-tetra-fluoro-benzo-nitrile in a coupling reaction was found to
      crystallize in the ortho-rhom-bic space group P212121. The two phenyl rings are
      rotated with respect to each other by 40.6 (6) degrees . The mol-ecules inter-act
      via aryl-perfluoroaryl stacking [3.796 (2) and 3.773 (2) A], resulting in inter
      molecular chains along the a-axis direction. C-H?F contacts of about 2.45 A
      connect these chains. In contrast to the structure of the parent compound 4'
      bromo-biphenyl-4-carbo-nitrile, CN?Br contacts that could have given rise to a
      linear arrangement of the biphenyl mol-ecules desirable for non-linear optical
      (NLO) materials are not observed in the packing. Instead, several Br?F [3.2405
      (17) and 3.2777 (18) A] and F?F [2.894 (2) A] contacts of side-on type II form an
      inter-molecular network of zigzag chains. The crystal studied was refined as an
      inversion twin. 

PMID- 25995942
TI  - Crystal structure of 4-bromo-2-[(E)-N-(2,2,6,6-tetra-methyl-piperidin-4
      yl)carboximido-yl]phenol dihydrate.
AB  - In the title hydrate, C16H23BrN2O.2H2O, the organic mol-ecule features a strong
      intra-molecular O-H?N hydrogen bond. The piperidine ring, in addition, adopts a
      chair conformation with the exocyclic C-N bond in an equatorial orientation. The
      water molecules of crystallization are disordered (each over two sets of sites
      with half occupancy. In the crystal, they associate into corrugated (100) sheets
      of (H2O)4 tetra-mers linked by O-H?O hydrogen bonds. The organic mol-ecules, in
      turn, are arranged at both sides of these sheets, linked by water-piperidine O
      H?N hydrogen bonds. 

PMID- 25995943
TI  - Crystal structure of 1,1'-{(dodecane-1,12-di-yl)bis-[(aza-niumylyl
      idene)methanylyl-idene]}bis-(naphthalen-2-olate).
AB  - The title compound, C34H40N2O2, exists in an extended conformation and has
      crystallographically imposed centrosymmetry. The crystal packing can be described
      as being composed of parallel layers stacked along [010]. The zwitterionic
      structure is stabilized by an intra-molecular N-H?O hydrogen-bond inter-action. 

PMID- 25995944
TI  - Crystal structure of N-(4-chloro-phen-yl)benzo-thio-amide.
AB  - The title compound, C13H10ClNS, exhibits a trans conformation with regard to the
      axis of the C-N bond. The benzene and phenyl rings are inclined to one another by
      85.06 (8) degrees . In the crystal, mol-ecules are linked by N-H?S=C hydrogen
      bonds, forming chains along [001]. 

PMID- 25995945
TI  - Crystal structure of 3-bromo-methyl-2-chloro-6-(di-bromo-meth-yl)quinoline.
AB  - In the title compound, C11H7Br3ClN, the quinoline ring system is approximately
      planar (r.m.s. = 0.011 A). In the crystal, mol-ecules are linked by C-H?Br inter
      actions forming chains along [10-1]. The chains are linked by C-H?pi and pi-pi
      inter-actions involving inversion-related pyridine rings [inter-centroid distance
      = 3.608 (4) A], forming sheets parallel to (10-1). Within the sheets, there are
      two significant short inter-actions involving a Br?Cl contact of 3.4904 (18) A
      and a Br?N contact of 3.187 (6) A, both of which are significantly shorter than
      the sum of their van der Waals radii. 

PMID- 25995946
TI  - Crystal structure of 2-methyl-N-[(4-methyl-pyridin-2-yl)carbamo-thio
      yl]benzamide.
AB  - In the title compound, C15H15N3OS, there is an intra-molecular N-H?O hydrogen
      bond and an intra-molecular C-H?S hydrogen bond involving the C=O and C=S bonds
      which lie on opposite sides of the mol-ecule. The mol-ecule is non-planar with
      the benzene and pyridine rings being inclined to one another by 26.86 (9) degrees
      . In the crystal, mol-ecules are linked by pairs of N-H?S hydrogen bonds, forming
      inversion dimers with an R 2 (2)(8) ring motif. The dimers are linked via C-H?S
      hydrogen bonds, forming slabs parallel to the bc plane. 

PMID- 25995947
TI  - Crystal structure of (E)-2-({[2-(1,3-dioxan-2-yl)phen-yl]imino}-meth-yl)phenol.
AB  - The title compound, C17H17NO3, prepared by the condensation reaction of 2-(1,3
      dioxan-2-yl)aniline and salicyl-aldehyde, has an E conformation about the C=N
      bond. The six-membered O-heterocycle adopts a chair conformation, with the bond
      to the aromatic ring located at its equatorial position. The dihedral angle
      between the aromatic rings is 36.54 (9) degrees . There is an intra-molecular N
      H?O hydrogen bond forming an S(6) ring motif. In the crystal, mol-ecules are
      linked by C-H?O hydrogen bonds, forming chains along the a-axis direction. Within
      the chains, there are C-H?pi inter-actions involving adjacent mol-ecules. 

PMID- 25995948
TI  - Crystal structure of 4-methyl-N-[2-(piperidin-1-yl)eth-yl]benzamide monohydrate.
AB  - In the title compound, C15H22N2O.H2O, the dihedral angle between the planes of
      the piperidine and benzene rings is 31.63 (1) degrees . The piperidine ring
      adopts a chair conformation. The water solvent mol-ecule is involved in inter
      species O-H?O, O-H?N, N-H?O and weak C-H?O hydrogen-bonding inter-actions, giving
      rise to chains extending along [010]. 

PMID- 25995949
TI  - Crystal structure of diiso-propyl-aminium di-chloro-acetate.
AB  - In the title compound, C6H16N(+).C2HCl2O2 (-), the cation exhibits non
      crystallographic C 2 symmetry. In the crystal, the components are linked by N-H?O
      and C-H?O hydrogen bonds into chains propagating along [010]. 

PMID- 25995950
TI  - Crystal structure of (E)-2-fluoro-benz-aldehyde (pyridin-2-yl)hydrazone.
AB  - The title compound, C12H10FN3, is approximately planar: the dihedral angles
      between the mean plane of the central N-N=C spacer unit and the fluoro-benzene
      and pyridine rings are 14.50 (13) and 4.85 (15) degrees , respectively, while the
      dihedral angle between the aromatic rings is 16.29 (6) degrees . The F atom lies
      at the same side of the mol-ecule as the N atom of the pyridine ring. In the
      crystal, inversion dimers linked by pairs of N-H?N hydrogen bonds generate R 2
      (2)(8) loops. Mol-ecules related by translation in the a direction are linked by
      two pi-pi stacking inter-actions involving pairs of benzene rings and pairs of
      pyridine rings. In each case, the ring-centroid separation is 3.8517 (9) A. Two
      chains of this type pass through each unit cell, but there are no direction
      specific inter-actions between adjacent chains. 

PMID- 25995951
TI  - Crystal structure of 2-chloro-3-(di-meth-oxy-meth-yl)-6-meth-oxy-quinoline.
AB  - The title compound, C13H14ClNO3, crystallizes with Z' = 2 in the space group
      Pca21, but a search for possible additional crystallographic symmetry found none.
      However, the crystal structure exhibits pseudosymmetry as the two independent mol
      ecules are related by an approximate but non-crystallographic inversion located
      close to (0.38, 0.26, 1/2) in the selected asymmetric unit, and the structure
      exhibits partial inversion twinning. The approximate inversion relationship
      between the two mol-ecules in the selected asymmetric unit is clearly shown by
      comparison of the relevant torsion angle in the two mol-ecules; the corresponding
      torsion angles have similar, although not identical magnitudes but with opposite
      signs. The mean planes of the quinoline rings in the two independent mol-ecules
      are almost parallel, with a dihedral angle of only 0.16 (3) degrees  between
      them, and the mutual orientation of these rings permits significant pi-pi
      stacking inter-actions between them [centroid-centroid distances = 3.7579 (15)
      and 3.7923 (15) A]. In addition, the bimolecular aggregates which are related by
      translation along [010] are linked by a further pi-pi stacking inter-action
      [centroid-centroid distance = 3.7898 (15) A], so forming a pi-stacked chain
      running parallel to [010]. However, there are no C-H?N hydrogen bonds in the
      structure nor, despite the number of independent aromatic rings, are there any C
      H?pi hydrogen bonds; hence there are no direction-specific inter-actions between
      adjacent pi-stacked chains. 

PMID- 25995952
TI  - Crystal structure of ethyl 2-amino-4-(4-meth-oxy-phen-yl)-4H-1-benzothieno[3,2
      b]pyran-3-carboxyl-ate.
AB  - The mol-ecule of the title compound, C21H19NO4S, features a fused ring system
      whereby a five-membered ring is flanked by two six-membered rings. This is linked
      to an ethyl 3-carboxyl-ate group and to a meth-oxy-benzene group. The fused-ring
      system is quasi-planar, with the greatest deviation from the mean plane being
      0.131 (1) A for the methine C atom. The plane through the meth-oxy-benzene ring
      is nearly perpendicular to that through the fused-ring system, as indicated by
      the dihedral angle of 85.72 (6) degrees . An intra-molecular N-H?O hydrogen bond
      is noted. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, forming
      layers that stack along the a axis. 

PMID- 25995953
TI  - Crystal structure of 2-butyl-sulfanyl-4,6-bis-[(E)-styr-yl]pyrimidine.
AB  - In the title compound, C24H24N2S, the dihedral angles between the central
      pyrimidine ring and pendant benzene rings are 18.46 (6) and 5.95 (6) degrees .
      The butyl-sulfanyl side chain adopts a twisted conformation [S-C-C-C = 177.34
      (10) degrees  and C-C-C-C = 67.68 (18) degrees ]. No directional inter-actions
      beyond typical van der Waals contacts could be identified in the crystal. 

PMID- 25995954
TI  - Crystal structure of 1-{3-acetyl-2-(4-chloro-phen-yl)-6-hy-droxy-4-[(2-hy-droxy
      prop-yl)amino]-6-methyl-cyclo-hex-3-en-1-yl}ethanone.
AB  - In the title compound, C20H26ClNO4, the central cyclo-hexene ring adopts an
      approximate envelope conformation with the C atom binding with the hy-droxy group
      at the tip of the flap. There is an intramolecular N-H?O hydrogen bond generating
      an S(6) ring motif. In the crystal, classical O-H?O hydrogen bonds and weak C-H?O
      and C-H?Cl inter-actions link the mol-ecules, forming a three-dimensional supra
      molecular architecture. The crystal structure was refined as a four-component
      twin. 

PMID- 25995955
TI  - Crystal structure of (E)-3-(3,4-di-meth-oxy-phen-yl)-1-(1-hy-droxy-naphthalen-2
      yl)prop-2-en-1-one.
AB  - The mol-ecular structure of the title compound, C21H18O4, consists of a 3,4-di
      meth-oxy-phenyl ring and a naphthalene ring system linked via a prop-2-en-1-one
      spacer. The mol-ecule is almost planar, with a dihedral angle between the benzene
      ring and the naphthalene ring system of 2.68 (12) degrees . There is an intra
      molecular O-H?O hydrogen bond involving the adjacent hy-droxy and carbonyl
      groups. The mol-ecule has an E conformation about the C=C bond and the carbonyl
      group is syn with respect to the C=C bond. In the crystal, mol-ecules are linked
      by bifurcated C-H?(O,O) hydrogen bonds, enclosing an R 2 (1)(6) ring motif, and
      by a further C-H?O hydrogen bond, forming undulating sheets extending in b- and c
      axis directions. There are pi-pi inter-actions between the sheets, involving
      inversion-related naphthalene and benzene rings [inter-centroid distance = 3.7452
      (17) A], forming a three-dimensional structure. 

PMID- 25995957
TI  - Health innovation for aging society.

PMID- 25995956
TI  - Spatial Variability of Escherichia coli in Rivers of Northern Coastal Ecuador.
AB  - The use of contaminated surface water continues to be a pressing issue in areas
      of the world where people lack improved drinking water sources. In northern
      coastal Ecuador, many communities rely on untreated surface water as their
      primary source of drinking water. We undertook a study to explore how microscale
      river hydrodynamics affect microbial water quality at community water collection
      locations at three rivers with varying stream velocity and turbidity profiles. To
      examine how the distance from river shore and physiochemical water quality
      variables affect microbial contamination levels in the rivers; we collected a
      total of 355 water samples within six villages on three rivers; and tested for
      Escherichia coli concentrations using the IDEXX Quanti-tray method. We found that
      log10E. coli concentrations decreased with increasing distance from shore (beta =
      -0.017; p = 0.003). Water in the main channel had E. coli concentrations on
      average 0.12 log10 lower than within eddies along the river shore and 0.27 log10
      lower between the sample closest to shore and any sample >6 m from the shore.
      Higher E. coli concentrations were also significantly associated with increased
      turbidity (beta = 0.003; p < 0.0001) and decreased dissolved oxygen levels (beta
      = -0.310; p < 0.0001). The results of this study can help inform community
      members about the safest locations to collect drinking water and also provide
      information on watershed scale transport of microbial contaminants between
      villages.

PMID- 25995958
TI  - Health and social media: perfect storm of information.
AB  - OBJECTIVES: The use of Internet in the health domain is becoming a major
      worldwide trend. Millions of citizens are searching online health information and
      also publishing content about their health. Patients are engaging with other
      patients in online communities using different types of social media. The
      boundaries between mobile health, social media, wearable, games, and big data are
      becoming blurrier due the integration of all those technologies. In this paper we
      provide an overview of the major research challenges with the area of health
      social media. METHODS: We use several study cases to exemplify the current trends
      and highlight future research challenges. RESULTS: Internet is exploding and is
      being used for health purposes by a great deal of the population. Social networks
      have a powerful influence in health decisions. Given the lack of knowledge on the
      use of health social media, there is a need for complex multidisciplinary
      research to help us understand how to use social networks in favour of public
      health. A bigger understanding of social media will give health authorities new
      tools to help decision-making at global, national, local, and corporate level.
      CONCLUSIONS: There is an unprecedented amount of data that can be used in public
      health due the potential combination of data acquired from mobile phones,
      Electronic Health Records, social media, and other sources. To identify
      meaningful information from those data sources it is not trial. Moreover, new
      analytics tools will need to be developed to analyse those sources of data in a
      way that it can benefit healthcare professionals and authorities.

PMID- 25995959
TI  - Factors affecting acceptance of smartphone application for management of obesity.
AB  - OBJECTIVES: The factors affecting the acceptance of mobile obesity-management
      applications (apps) by the public were analyzed using a mobile healthcare system
      (MHS) technology acceptance model (TAM). METHODS: The subjects who participated
      in this study were Android smartphone users who had an intent to manage their
      weight. They used the obesity-management app for two weeks, and then completed an
      18-item survey designed to determine the factors influencing the acceptance of
      the app. Three questions were asked pertaining to each of the following six
      factors: compatibility, self-efficacy, technical support and training, perceived
      usefulness, perceived ease of use, and behavior regarding intention to use.
      Cronbach's alpha was used to assess the reliability of the scales. Pathway
      analysis was also performed to evaluate the MHS acceptance model. RESULTS: A
      total of 94 subjects participated in this study. The results indicate that
      compatibility, perceived usefulness, and perceived ease of use significantly
      affected the behavioral intention to use the mobile obesity-management app.
      Technical support and training also significantly affected the perceived ease of
      use; however, the hypotheses that self-efficacy affects perceived usefulness and
      perceived ease of use were not supported in this study. CONCLUSIONS: This is the
      first attempt to analyze the factors influencing mobile obesity-management app
      acceptance using a TAM. Further studies should cover not only obesity but also
      other chronic diseases and should analyze the factors affecting the acceptance of
      apps among healthcare consumers in general.

PMID- 25995960
TI  - Development of Cell Phone Application for Blood Glucose Self-Monitoring Based on
      ISO/IEEE 11073 and HL7 CCD.
AB  - OBJECTIVES: The objectives of this research were to develop and evaluate a cell
      phone application based on the standard protocol for personal health devices and
      the standard information model for personal health records to support effective
      blood glucose management and standardized service for patients with diabetes.
      METHODS: An application was developed for Android 4.0.3. In addition, an IEEE
      11073 Manager, Medical Device Encoding Rule, and Bluetooth Health Device Profile
      Connector were developed for standardized health communication with a glucometer,
      and a Continuity of Care Document (CCD) Composer and CCD Parser were developed
      for CCD document exchange. The developed application was evaluated by five
      healthcare professionals and 87 users through a questionnaire comprising the
      following variables: usage intention, effort expectancy, social influence,
      facilitating condition, perceived risk, and voluntariness. RESULTS: As a result
      of the evaluation of usability, it was confirmed that the developed application
      is useful for blood glucose self-monitoring by diabetic patients. In particular,
      the healthcare professionals stated their own views that the application is
      useful to observe the trends in blood glucose change through the automatic
      function which records a blood glucose level measured using Bluetooth function,
      and the function which checks accumulated records of blood glucose levels. Also,
      a result of the evaluation of usage intention was 3.52 +/- 0.42 out of 5 points.
      CONCLUSIONS: The application developed by our research team was confirmed by the
      verification of healthcare professionals that accurate feedback can be provided
      to healthcare professionals during the management of diabetic patients or
      education for glucose management.

PMID- 25995961
TI  - Implementation of hospital examination reservation system using data mining
      technique.
AB  - OBJECTIVES: New methods for obtaining appropriate information for users have been
      attempted with the development of information technology and the Internet. Among
      such methods, the demand for systems and services that can improve patient
      satisfaction has increased in hospital care environments. METHODS: In this paper,
      we proposed the Hospital Exam Reservation System (HERS), which uses the data
      mining method. First, we focused on carrying clinical exam data and finding the
      optimal schedule for generating rules using the multi-examination pattern-mining
      algorithm. Then, HERS was applied by a rule master and recommending system with
      an exam log. Finally, HERS was designed as a user-friendly interface. RESULTS:
      HERS has been applied at the National Cancer Center in Korea since June 2014. As
      the number of scheduled exams increased, the time required to schedule more than
      a single condition decreased (from 398.67% to 168.67% and from 448.49% to
      188.49%; p < 0.0001). As the number of tests increased, the difference between
      HERS and non-HERS increased (from 0.18 days to 0.81 days). CONCLUSIONS: It was
      possible to expand the efficiency of HERS studies using mining technology in not
      only exam reservations, but also the medical environment. The proposed system
      based on doctor prescription removes exams that were not executed in order to
      improve recommendation accuracy. In addition, we expect HERS to become an
      effective system in various medical environments.

PMID- 25995962
TI  - Architecture Design of Healthcare Software-as-a-Service Platform for Cloud-Based
      Clinical Decision Support Service.
AB  - OBJECTIVES: To design a cloud computing-based Healthcare Software-as-a-Service
      (SaaS) Platform (HSP) for delivering healthcare information services with low
      cost, high clinical value, and high usability. METHODS: We analyzed the
      architecture requirements of an HSP, including the interface, business services,
      cloud SaaS, quality attributes, privacy and security, and multi-lingual capacity.
      For cloud-based SaaS services, we focused on Clinical Decision Service (CDS)
      content services, basic functional services, and mobile services. Microsoft's
      Azure cloud computing for Infrastructure-as-a-Service (IaaS) and Platform-as-a
      Service (PaaS) was used. RESULTS: The functional and software views of an HSP
      were designed in a layered architecture. External systems can be interfaced with
      the HSP using SOAP and REST/JSON. The multi-tenancy model of the HSP was designed
      as a shared database, with a separate schema for each tenant through a single
      application, although healthcare data can be physically located on a cloud or in
      a hospital, depending on regulations. The CDS services were categorized into rule
      based services for medications, alert registration services, and knowledge
      services. CONCLUSIONS: We expect that cloud-based HSPs will allow small and mid
      sized hospitals, in addition to large-sized hospitals, to adopt information
      infrastructures and health information technology with low system operation and
      maintenance costs.

PMID- 25995963
TI  - Wave detection in acceleration plethysmogram.
AB  - OBJECTIVES: Acceleration plethysmogram (APG) obtained from the second derivative
      of photoplethysmography (PPG) is used to predict risk factors for atherosclerosis
      with age. This technique is promising for early screening of atherosclerotic
      pathologies. However, extraction of the wave indices of APG signals measured from
      the fingertip is challenging. In this paper, the development of a wave detection
      algorithm including a preamplifier based on a microcontroller that can detect the
      a, b, c, and d wave indices is proposed. METHODS: The 4(th) order derivative of a
      PPG under real measurements of an APG waveform was introduced to clearly separate
      the components of the waveform, and to improve the rate of successful wave
      detection. A preamplifier with a Sallen-Key low pass filter and a wave detection
      algorithm with programmable gain control, mathematical differentials, and a
      digital IIR notch filter were designed. RESULTS: The frequency response of the
      digital IIR filter was evaluated, and a pulse train consisting of a specific area
      in which the wave indices existed was generated. The programmable gain control
      maintained a constant APG amplitude at the output for varying PPG amplitudes. For
      164 subjects, the mean values and standard deviation of the a wave index
      corresponding to the magnitude of the APG signal were 1,106.45 and +/-47.75,
      respectively. CONCLUSIONS: We conclude that the proposed algorithm and
      preamplifier designed to extract the wave indices of an APG in real-time are
      useful for evaluating vascular aging in the cardiovascular system in a simple
      healthcare device.

PMID- 25995964
TI  - Effects of health information technology on malpractice insurance premiums.
AB  - OBJECTIVES: The widespread adoption of health information technology (IT) will
      help contain health care costs by decreasing inefficiencies in healthcare
      delivery. Theoretically, health IT could lower hospitals' malpractice insurance
      premiums (MIPs) and improve the quality of care by reducing the number and size
      of malpractice. This study examines the relationship between health IT investment
      and MIP using California hospital data from 2006 to 2007. METHODS: To examine the
      effect of hospital IT on malpractice insurance expense, a generalized estimating
      equation (GEE) was employed. RESULTS: It was found that health IT investment was
      not negatively associated with MIP. Health IT was reported to reduce medical
      error and improve efficiency. Thus, it may reduce malpractice claims from
      patients, which will reduce malpractice insurance expenses for hospitals.
      However, health IT adoption could lead to increases in MIPs. For example, we
      expect increases in MIPs of about 1.2% and 1.5%, respectively, when health IT and
      labor increase by 10%. CONCLUSIONS: This study examined the effect of health IT
      investment on MIPs controlling other hospital and market, and volume
      characteristics. Against our expectation, we found that health IT investment was
      not negatively associated with MIP. There may be some possible reasons that the
      real effect of health IT on MIPs was not observed; barriers including
      communication problems among health ITs, shorter sample period, lower IT
      investment, and lack of a quality of care measure as a moderating variable.

PMID- 25995965
TI  - Effects of mobile phone-based app learning compared to computer-based web
      learning on nursing students: pilot randomized controlled trial.
AB  - OBJECTIVES: This study aimed to determine the effect of mobile-based discussion
      versus computer-based discussion on self-directed learning readiness, academic
      motivation, learner-interface interaction, and flow state. METHODS: This
      randomized controlled trial was conducted at one university. Eighty-six nursing
      students who were able to use a computer, had home Internet access, and used a
      mobile phone were recruited. Participants were randomly assigned to either the
      mobile phone app-based discussion group (n = 45) or a computer web-based
      discussion group (n = 41). The effect was measured at before and after an online
      discussion via self-reported surveys that addressed academic motivation, self
      directed learning readiness, time distortion, learner-learner interaction,
      learner-interface interaction, and flow state. RESULTS: The change in extrinsic
      motivation on identified regulation in the academic motivation (p = 0.011) as
      well as independence and ability to use basic study (p = 0.047) and positive
      orientation to the future in self-directed learning readiness (p = 0.021) from
      pre-intervention to post-intervention was significantly more positive in the
      mobile phone app-based group compared to the computer web-based discussion group.
      Interaction between learner and interface (p = 0.002), having clear goals (p =
      0.012), and giving and receiving unambiguous feedback (p = 0.049) in flow state
      was significantly higher in the mobile phone app-based discussion group than it
      was in the computer web-based discussion group at post-test. CONCLUSIONS: The
      mobile phone might offer more valuable learning opportunities for discussion
      teaching and learning methods in terms of self-directed learning readiness,
      academic motivation, learner-interface interaction, and the flow state of the
      learning process compared to the computer.

PMID- 25995966
TI  - Development of individual survival estimating program for cancer patients'
      management.
AB  - OBJECTIVES: The goal of this report is to present an individual patient's
      survival estimation curve using the each institution's survival data after Cox
      proportional hazard analysis. METHODS: The program was developed in three parts:
      input of basic data from Cox proportional hazard analysis, input of individual
      patient's covariates, and presentation of individual patient's survival curve. In
      the first part, the average survival rates with each survival time were entered
      as the means of covariates using the results of Cox proportional hazard analysis.
      In the second part, the individual patient's values of each covariate were
      entered for the calculation of survival estimation. In the third part, the
      survival curve was displayed according to the input data. RESULTS: The data of
      2,652 breast cancer patients were analyzed. Cox regression analysis was conducted
      using the covariates of age, tumor size, N stage, and M stage. The individual
      patient's survival curve was presented using the basic data and covariate
      factors. In the breast cancer patients, the program presented survival curves
      according to each patient's age, tumor size, N stage, and M stage. The data of
      251 thyroid cancer patients were analyzed by a similar method. CONCLUSIONS: We
      developed a program to present individual survival curves of cancer patients.
      This program will be useful for clinicians to assist their decision-making and
      discussion with patients.

PMID- 25995967
TI  - Vancomycin continuous infusion versus intermittent infusion during continuous
      venovenous hemofiltration: slow and steady may win the race.
AB  - BACKGROUND: Vancomycin during continuous venovenous hemofiltration (CVVH) is
      either administered by intermittent infusion (II) or continuous infusion (CI). In
      this patient population, the best method to rapidly achieve target serum
      concentrations of 15 mcg/ml to 25 mcg/ml remains to be elucidated. We
      hypothesized that CI would achieve a target serum level of 15 mcg/ml to 25 mcg/ml
      within 24 h of the initiation of therapy more consistently than II. METHODS: A
      retrospective cohort study of adult patients admitted to the intensive care unit
      (ICU) between 2011 and 2014 receiving intravenous vancomycin with 24-hour serum
      level while on CVVH was included. Patients were excluded from this review if they
      had residual renal function during CVVH, were concomitantly on extracorporeal
      membrane oxygenation, or if the first dose of vancomycin was received six or more
      hours prior to the initiation of CVVH. The primary outcome was the achievement of
      a therapeutic level of 15mcg/ml to 25 mcg/ml by 24 hours. RESULTS: Fifty-nine
      patients met the inclusion criteria and 14 received CI and 45 in II. Therapeutic
      24-hour levels were achieved in 14/14 versus 2/45 in CI and II, respectively (p <
      0.001). Mean 24-hour vancomycin levels were 20.35 +/- 2.78 mcg/ml for CI compared
      to 9.7 +/- 3.52 mcg/ml for II (p < 0.001). Mean loading dose was 26.65 +/- 3.06
      mg/kg for CI compared to 17.58 +/- 5.72 mg/kg for II (p < 0.001). Daily
      maintenance doses were 15.66 +/- 6.26 mg/kg for CI compared to 17.28 +/- 4.96
      mg/kg for II (p = 0.339). In the subgroup of 27 patients who received vancomycin
      loading dose >20 mg/kg, mean 24-hour levels were 20.35 +/- 2.78 mcg/ml for CI
      versus 11.8 +/- 2.7 mcg/ml for II (p < 0.001). No significant differences were
      found between patients in the two groups with respect to CVVH rate and length of
      CVVH prior to vancomycin administration. CONCLUSIONS: The results of our study
      suggest that critically ill patients on CVVH treated with CI achieved the target
      level faster than II and consistently keep the vancomycin level within target
      range.

PMID- 25995968
TI  - Preclinical and Clinical Studies for Sodium Tungstate: Application in Humans.
AB  - Diabetes is a complex metabolic disorder triggered by the deficient secretion of
      insulin by the pancreatic beta-cell or the resistance of peripheral tissues to
      the action of the hormone. Chronic hyperglycemia is the major consequence of this
      failure, and also the main cause of diabetic problems. Indeed, several clinical
      trials have agreed in that tight glycemic control is the best way to stop
      progression of the disease. Many anti-diabetic drugs for treatment of type 2
      diabetes are commercially available, but no ideal normoglycemic agent has been
      developed yet. Moreover, weight gain is the most common side effect of many oral
      anti-diabetic agents and insulin, and increased weight has been shown to worsen
      glycemic control and increase the risk of diabetes progression. In this sense,
      the inorganic salt sodium tungstate (NaW) has been studied in different animal
      models of metabolic syndrome and diabetes, proving to have a potent effect on
      normalizing blood glucose levels and reducing body weight, without any
      hypoglycemic action. Although the liver has been studied as the main site of NaW
      action, positive effects have been also addressed in muscle, pancreas, brain,
      adipose tissue and intestine, explaining the effective anti-diabetic action of
      this salt. Here, we review NaW research to date in these different target organs.
      We believe that NaW deserves more attention, since all available anti-diabetic
      treatments remain suboptimal and new therapeutics are urgently needed.

PMID- 25995969
TI  - Delivering Oxidation Resistance-1 (OXR1) to Mouse Kidney by Genetic Modified
      Mesenchymal Stem Cells Exhibited Enhanced Protection against Nephrotoxic Serum
      Induced Renal Injury and Lupus Nephritis.
AB  - OBJECTIVE: To elucidate the role of oxidation resistance 1 (OXR1) gene. Oxidative
      stress plays a pivotal role in pathogenesis of immune-mediated nephritis.
      Recently we identified oxidation resistance 1 (OXR1) is conventionally expressed
      in eukaryotes and has an ability to prevent oxidative damage caused by various
      oxidative stresses. However the protective effect of OXR1 in immune-associated
      inflammatory response and oxidative damage is not clear and will be investigated
      in this study. METHODS: We utilized mesenchymal stem cells (MSCs) as vehicles to
      carry OXR1 into the injured kidneys of nephritis model mice and investigated the
      influence of OXR1 on glomerulonephritis. Human OXR1 gene was integrated into
      genome of MSCs via lentiviral vector, and established hOXR1-MSC cell line which
      still maintains the differentiation property. 129/svj mice with anti-glomerular
      basement membrane (GBM) challenge and spontaneous lupus mice B6.Sle1.Sle2.Sle3
      were injected with hOXR1-MSCs (i.v. injection) to evaluate the function of hOXR1.
      Immunohistochemistry was used to appraise the renal pathology and Tunel staining
      was applied to detect cell apoptosis. RESULTS: Compared with control mice, hOXR1
      MSCs administration showed significantly decreased blood urea nitrogen (BUN),
      proteinuria and ameliorated renal pathological damage. hOXR1-MSCs transplantation
      significantly reduced macrophage and T lymphocyte infiltration by inhibiting the
      expression of CCL2, CCL7, IL-1beta, IL-6 and NFkappaB in mouse kidney. Moreover,
      hOXR1-MSCs prevented hydrogen peroxide (H2O2)-induced oxidative stress and its
      implantation reduced nitric oxide (NO) in mouse serum and urine to inhibit
      tubular cell apoptosis. CONCLUSION: OXR1-MSCs transplantation may exert a certain
      protective effect on nephritis by suppressing inflammation and oxidative stress.

PMID- 25995970
TI  - Quantitative intravital two-photon excitation microscopy reveals absence of
      pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice.
AB  - Sickle cell disease (SCD) is a genetic disorder that leads to red blood cell
      (RBC) sickling, hemolysis and the upregulation of adhesion molecules on sickle
      RBCs. Chronic hemolysis in SCD results in a hyper-inflammatory state
      characterized by activation of circulating leukocytes, platelets and endothelial
      cells even in the absence of a crisis. A crisis in SCD is often triggered by an
      inflammatory stimulus and can lead to the acute chest syndrome (ACS), which is a
      type of lung injury and a leading cause of mortality among SCD patients. Although
      it is believed that pulmonary vaso-occlusion could be the phenomenon contributing
      to the development of ACS, the role of vaso-occlusion in ACS remains elusive.
      Intravital imaging of the cremaster microcirculation in SCD mice has been
      instrumental in establishing the role of neutrophil-RBC-endothelium interactions
      in systemic vaso-occlusion; however, such studies, although warranted, have never
      been done in the pulmonary microcirculation of SCD mice. Here, we show that two
      photon excitation fluorescence microscopy can be used to perform quantitative
      analysis of neutrophil and RBC trafficking in the pulmonary microcirculation of
      SCD mice. We provide the experimental approach that enables microscopic
      observations under physiological conditions and use it to show that RBC and
      neutrophil trafficking is comparable in SCD and control mice in the absence of an
      inflammatory stimulus. The intravital imaging scheme proposed in this study can
      be useful in elucidating the cellular and molecular mechanism of pulmonary vaso
      occlusion in SCD mice following an inflammatory stimulus.

PMID- 25995971
TI  - The Effect of Race/Ethnicity on the Age of Colon Cancer Diagnosis.
AB  - BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in the
      United States. Notably, racial/ethnic disparities exist in both incidence and
      mortality. PURPOSE: The aim of this case study was to investigate the impact of
      race/ethnicity on age at diagnosis of colorectal cancer in a defined population
      in Suffolk County, NY. METHODS: Data were retrospectively collected on
      race/ethnicity, health insurance status, age at diagnosis, stage at diagnosis,
      gender, smoking status, alcohol intake, tumor location, and body mass index for
      colorectal cancer patients with medical records in the Stony Brook University
      Medical Center database (2005-2011). Population-based data on Hispanic and non
      Hispanic Whites were obtained from the Surveillance, Epidemiology, and End
      Results registry of New York State for an overlapping time period. Permutation
      based ANCOVA and logistic regression with stepwise variable selection were
      conducted to identify covariates and first-order interactions associated with
      younger age at diagnosis and cancer stage as a dependent categorical variable.
      RESULTS: Of 328 colorectal cancer patients, Hispanics were diagnosed at a median
      younger age of 57y vs. 67y than non-Hispanic Whites (FDR = 0.001). Twenty-six
      percent of Hispanics were diagnosed with colorectal cancer prior to the
      recommended age (50y) for colorectal cancer surveillance compared to 11% of non
      Hispanic Whites (FDR =0.007). Analysis of New York State registry data
      corroborated our findings that Hispanic colorectal cancer patients were diagnosed
      at a median younger age than non-Hispanic Whites. Permutation-based ANCOVA
      identified race/ethnicity and health insurance as significantly associated with
      age of diagnosis (P=0.001). Logistic regression selected (younger) age at
      diagnosis as being significantly associated with stage IV disease. The
      limitations of the case study reside in the use of self-reporting of race and
      ethnicity and in the small sample sizes. CONCLUSIONS: Hispanics may be at higher
      risk for colorectal cancer (<50>y) and younger age at diagnosis is associated
      with advanced disease.

PMID- 25995972
TI  - American Indian Men's Perceptions of Breast Cancer Screening for American Indian
      Women.
AB  - Screening, especially screening mammography, is vital for decreasing breast
      cancer incidence and mortality. Screening rates in American Indian women are low
      compared to other racial/ethnic groups. In addition, American Indian women are
      diagnosed at more advanced stages and have lower 5-year survival rate than
      others. To better address the screening rates of American Indian women, focus
      groups (N=8) were conducted with American Indian men (N=42) to explore their
      perceptions of breast cancer screening for American Indian women. Our intent was
      to understand men's support level toward screening. Using a community-based
      participatory approach, focus groups were audio-taped, transcribed verbatim, and
      analyzed using a text analysis approach developed by our team. Topics discussed
      included breast cancer and screening knowledge, barriers to screening, and
      suggestions to improve screening rates. These findings can guide strategies to
      improve knowledge and awareness, communication among families and health care
      providers, and screening rates in American Indian communities.

PMID- 25995973
TI  - The road to cure in multiple myeloma starts with smoldering disease.
AB  - INTRODUCTION: Smoldering multiple myeloma (SMM) is a heterogeneous clinical
      entity that defines patients in the spectrum of disease progression from
      monoclonal gammopathy of undetermined significance to multiple myeloma (MM).
      Current standard of care is observation until end organ damage occurs. In spite
      of this, the scientific community has begun to question whether the strategy of
      watchful waiting should be replaced with earlier therapeutic intervention with
      the ultimate goal of preventing clonal heterogeneity and end organ damage. AREAS
      COVERED: In this review, we challenge the concept of observation as the best
      option of therapy in SMM. We present current data on diagnosis, prognostic
      factors of disease progression and studies that have been conducted to date to
      determine whether earlier therapeutic interventions will lead to an improvement
      in overall survival of patients with MM. EXPERT OPINION: If the recommendations
      of treatment of SMM were to change, the scientific body of evidence would have to
      overcome four major hurdles: to demonstrate that early intervention leads to
      prolonged survival and delay in development of end organ damage, that it does not
      have long-term toxicities, that it is implemented in patients with a high
      likelihood of developing myeloma and that it does not lead to the outgrowth of
      more resistant clones. Only well-designed clinical trials will determine whether
      cure can be achieved with earlier interventions.

PMID- 25995974
TI  - PHENIX: An R package to estimate a size-controlled phenotypic integration index.
AB  - PREMISE OF THE STUDY: Organisms usually show intercorrelations between all or
      some of their components leading to phenotypic integration, which may have deep
      consequences on the evolution of phenotypes. One of the main difficulties with
      phenotypic integration studies is how to correct the integration measures for
      size. This has been considered a challenging task. In this paper, we introduce an
      R package (PHENIX: PHENotypic Integration indeX), in which we provide functions
      to estimate a size-controlled phenotypic integration index, a bootstrapping
      method to calculate confidence intervals, and a randomization method to simulate
      null distributions and test the statistical significance of the integration.
      METHODS AND RESULTS: PHENIX is an open source package written in R. As usual for
      R packages, the manual and sample data are available at: http://cran.r
      project.org/web/packages/PHENIX/index.html. Functions included in this package
      easily estimate phenotypic integration by controlling a third variable (e.g., the
      size of the studied organ). CONCLUSIONS: PHENIX helps to estimate and test the
      statistical significance of the magnitude of integration using one of the most
      used methodological approaches, while taking size into account.

PMID- 25995975
TI  - Modified CTAB and TRIzol protocols improve RNA extraction from chemically complex
      Embryophyta.
AB  - PREMISE OF THE STUDY: Here we present a series of protocols for RNA extraction
      across a diverse array of plants; we focus on woody, aromatic, aquatic, and other
      chemically complex taxa. METHODS AND RESULTS: Ninety-one taxa were subjected to
      RNA extraction with three methods presented here: (1) TRIzol/TURBO DNA-free kits
      using the manufacturer's protocol with the addition of sarkosyl; (2) a
      combination method using cetyltrimethylammonium bromide (CTAB) and
      TRIzol/sarkosyl/TURBO DNA-free; and (3) a combination of CTAB and QIAGEN RNeasy
      Plant Mini Kit. Bench-ready protocols are given. CONCLUSIONS: After an iterative
      process of working with chemically complex taxa, we conclude that the use of
      TRIzol supplemented with sarkosyl and the TURBO DNA-free kit is an effective,
      efficient, and robust method for obtaining RNA from 100 mg of leaf tissue of land
      plant species (Embryophyta) examined. Our protocols can be used to provide RNA of
      suitable stability, quantity, and quality for transcriptome sequencing.

PMID- 25995976
TI  - Application of digital field photographs as documents for tropical plant
      inventory.
AB  - PREMISE OF THE STUDY: We tested the credibility and significance of digital field
      photographs as supplements or substitutes for conventional herbarium specimens
      with particular relevance to exploration of the tropics. METHODS: We made 113
      collections in triplicate at a species-rich mountain in the Philippines while we
      took 1238 digital photographs of the same plants. We then identified the plants
      from the photographs alone, categorized the confidence of the identification and
      the reason for failure to identify, and compared the results to identifications
      based on the dried specimens. RESULTS: We identified 72.6% of the photographic
      sets with high confidence and 27.4% with low confidence or only to genus. In no
      case was a confident identification altered by subsequent examination of the
      dried specimen. The failure to identify photographic sets to species was due to
      the lack of a key feature in 67.8% of the cases and due to a poorly understood
      taxonomy in 32.2%. DISCUSSION: We conclude that digital photographs cannot
      replace traditional herbarium specimens as the primary elements that document
      tropical plant diversity. However, photographs represent a new and important
      artifact that aids an expedient survey of tropical plant diversity while
      encouraging broad public participation.

PMID- 25995977
TI  - Development of microsatellite primers in the protected species Viola elatior
      (Violaceae) using next-generation sequencing.
AB  - PREMISE OF THE STUDY: Viola elatior (Violaceae) is a Eurasian perennial plant
      species in which French populations are threatened by anthropogenic pressures.
      Microsatellite primers were developed to investigate its genetic structure and
      diversity. METHODS AND RESULTS: Eight microsatellite markers were isolated using
      next-generation sequencing. Loci were amplified and screened for 138 individuals
      in 17 populations from France. Two of the eight polymorphic loci presented no
      variability across populations. The total number of alleles per locus varied from
      two to four. Observed heterozygosity ranged from 0.051 to 1.000. All primers
      amplified successfully in the closely related species V. pumila. CONCLUSIONS:
      This set of microsatellites offers a valuable tool for assessing population
      genetic diversity of the species to improve its conservation and base management
      efforts. High observed heterozygosity values probably reflect the particular
      mating system of the species and suggest an important tendency to clonality.

PMID- 25995978
TI  - Development of 18 polymorphic microsatellite markers for Vinca minor
      (Apocynaceae) via 454 pyrosequencing.
AB  - PREMISE OF THE STUDY: Polymorphic microsatellite markers were developed in Vinca
      minor (Apocynaceae) to evaluate the level of clonality, population structure, and
      genetic diversity of the species within its native and introduced range. METHODS
      AND RESULTS: A total of 1371 microsatellites were found in 43,565 reads from 454
      pyrosequencing of genomic V. minor DNA. Additional microsatellite loci were mined
      from publicly available cDNA sequences. After several rounds of screening, 18
      primer pairs flanking di-, tri-, or tetranucleotide repeats were identified that
      revealed high levels of genetic diversity in two native Italian populations, with
      two to 11 alleles per locus. Clonal growth predominated in two populations from
      the introduced range in Germany. Five loci successfully cross-amplified in three
      additional Vinca species. CONCLUSIONS: The novel polymorphic microsatellite
      markers are promising tools for studying clonality and population genetics of V.
      minor and for assessing the historical origin of Central European populations.

PMID- 25995979
TI  - Development of 23 polymorphic microsatellite loci in invasive silver wattle,
      Acacia dealbata (Fabaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for silver wattle,
      Acacia dealbata (Fabaceae), which is both an ornamental and an invasive weed
      species. It is native to southeastern Australia and invasive in Europe, Africa,
      Asia, and the Americas. METHODS AND RESULTS: The pyrosequencing of a
      microsatellite-enriched genomic DNA library of A. dealbata produced 33,290
      sequences and allowed the isolation of 201 loci with a minimum of seven repeats
      of microsatellite motifs. Amplification tests led to the setup of two multiplex
      PCR mixes allowing the amplification of 21 loci. The polymorphism of these
      markers was evaluated on a sample of 32 individuals collected in southeastern
      Australia. The number of alleles and the expected heterozygosity varied between
      two and 11, and between 0.11 and 0.88, respectively. CONCLUSIONS: The level of
      polymorphism of this set of 23 microsatellites is large enough to provide
      valuable information on the genetic structure and the invasion history of A.
      dealbata.

PMID- 25995980
TI  - Isolation and characterization of 12 microsatellite loci in soapbark, Quillaja
      saponaria (Quillajaceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for the endemic
      Chilean tree Quillaja saponaria (Quillajaceae), a common member of the
      sclerophyllous Mediterranean forest, to investigate intraspecific patterns of
      genetic diversity and structure. METHODS AND RESULTS: Using an enriched library,
      12 polymorphic microsatellite loci were developed in Q. saponaria. All loci
      consisted of dinucleotide repeats. The average number of alleles per locus was
      5.3 (2-13), with a total of 64 alleles recorded in 39 individuals from three
      populations. CONCLUSIONS: The microsatellite markers described here are the first
      characterized for Q. saponaria. The polymorphic loci will be useful in studies of
      genetic diversity and genetic population differentiation in natural populations
      of this species.

PMID- 25995981
TI  - Microbial inhibition of oral epithelial wound recovery: potential role for quorum
      sensing molecules?
AB  - Awareness of the impact of microbiota in both health and disease is growing.
      Using a new in vitro oral mucosa co-culture model, we recently showed a clear
      inhibition of epithelial wound healing in the presence of an oral microbial
      community. In this paper, we have used the same model in combination with
      specific oral microbial species to obtain a better insight into the role of the
      oral microbiota in wound healing. Monocultures of Klebsiella oxytoca and
      Lactobacillus salivarius significantly inhibited wound healing with ~20%, whereas
      Streptococcus mitis and S. oralis enhanced the healing process with ~15% in 24 h.
      Yet, neither S. oralis or S. mitis were able to counteract the inhibitory effects
      from K. oxytoca on wound healing. Other tested microbial species had no effect on
      wound healing. Apart from this species-dependency, the inhibitory effect on wound
      healing depended on a microbial threshold concentration. Further mechanistic
      experiments with K. oxytoca excluded different microbial factors and hypothesized
      that quorum sensing molecules might play a role in the inter-kingdom signalling
      during wound healing. These results are important for the development of new
      strategies for the management of (infected) wounds and ulcerations. 

PMID- 25995982
TI  - The McDonald exponentiated gamma distribution and its statistical properties.
AB  - In this paper, we propose a five-parameter lifetime model called the McDonald
      exponentiated gamma distribution to extend beta exponentiated gamma, Kumaraswamy
      exponentiated gamma and exponentiated gamma, among several other models. We
      provide a comprehensive mathematical treatment of this distribution. We derive
      the moment generating function and the rth moment. We discuss estimation of the
      parameters by maximum likelihood and provide the information matrix. AMS SUBJECT
      CLASSIFICATION: Primary 62N05; secondary 90B25.

PMID- 25995983
TI  - Founding weaver ant queens (Oecophylla longinoda) increase production and nanitic
      worker size when adopting non-nestmate pupae.
AB  - Weaver ants (Oecophylla longinoda Latreille) are used commercially to control
      pest insects and for protein production. In this respect fast colony growth is
      desirable for managed colonies. Transplantation of non-nestmate pupae to
      incipient colonies has been shown to boost colony growth. Our objectives were to
      find the maximum number of pupae a founding queen can handle, and to measure the
      associated colony growth. Secondly, we tested if transplantation of pupae led to
      production of larger nanitic workers (defined as unusually small worker ants
      produced by founding queens in their first batch of offspring). Forty-five
      fertilized queens were divided into three treatments: 0 (control), 100 or 300 non
      nestmate pupae transplanted to each colony. Pupae transplantation resulted in
      highly increased growth rates, as pupae were readily adopted by the queens and
      showed high proportions of surviving (mean = 76%). However, survival was
      significantly higher when 100 pupae were transplanted compared to transplantation
      of 300 pupae, indicating that queens were unable to handle 300 pupae adequately
      and that pupae require some amount of nursing. Nevertheless, within the 60-day
      experiment the transplantation of 300 pupae increased total colony size more than
      10-fold whereas 100 pupae increased the size 5.6 fold, compared to control. This
      increase was due not only to the individuals added in the form of pupae but also
      to an increased per capita brood production by the resident queen, triggered by
      the adopted pupae. The size of hatching pupae produced by the resident queen also
      increased with the number of pupae transplanted, leading to larger nanitic
      workers in colonies adopting pupae. In conclusion, pupae transplantation may be
      used to produce larger colonies with larger worker ants and may thus reduce the
      time to produce weaver ant colonies for commercial purposes. This in turn may
      facilitate the implementation of the use of weaver ants. 

PMID- 25995984
TI  - Women with large (>=3 cm) and locally advanced breast cancers (T3, 4, N1, 2, M0)
      receiving neoadjuvant chemotherapy (NAC: cyclophosphamide, doxorubicin,
      docetaxel): addition of capecitabine improves 4-year disease-free survival.
AB  - PURPOSE: To determine whether capecitabine (X), combined with docetaxel (T)
      following doxorubicin (A) and cyclophosphamide (C), enhanced the pathological
      complete response (pCR) in the breast and axillary lymph nodes (ALNs) of women
      with large or locally advanced breast cancers (LLABCs) improving outcome, and the
      effect on quality of life (QoL). PATIENTS AND METHODS: 117 women were enrolled,
      112 randomised to 2 cycles of AC (60 mg/m(2), 600 mg/m(2)) given 3 weekly. Tumour
      responses were assessed by magnetic resonance mammography. Responders (n = 77)
      received 2 further cycles of AC and were randomised to 4 cycles of T (100
      mg/m(2)) (Group A) or T (75 mg/m(2)) and X (2000 mg/m(2)/day), day one to 14 of
      each 3 weekly cycle (Group B). Non-responders (n = 35) were randomised to 6
      cycles of T (Group C) or T + X (Group D). QoL questionnaires were completed at
      each chemotherapy visit. Pathological responses were evaluated using established
      criteria. RESULTS: The groups were comparable in patient and tumour
      characteristics (79.5% T2, 85.7% ductal, 73.2% ER +ve, 22.3% HER2 +ve, 42%
      involved ALNs). Overall breast pCR was 27.1%, Groups A + C versus B + D (p =
      0.446). ALN +ve pCR was 41.9%, Groups A + C versus B + D (p = 0.231). 4-year
      disease-free survival (DFS) was significantly improved with X (p = 0.016) but not
      overall survival (p = 0.056). Triple -ve and HER2 +ve tumours, and persistent ALN
      disease were risk factors for metastases. X increased severe nail changes (p =
      0.0002) and hand-foot syndrome (p = 0.014) without affecting QoL. CONCLUSION: NAC
      X did not increase breast and ALN pCR but improved 4-year DFS, without detriment
      to QoL.

PMID- 25995985
TI  - Malaria Vaccines: Moving Forward After Encouraging First Steps.
AB  - An effective malaria vaccine that reduces morbidity and mortality and contributes
      to malaria elimination is a much-needed tool, particularly in endemic areas where
      health-care delivery and vector control efforts are difficult to sustain.
      RTS,S/AS01 is likely to be the first licensed malaria vaccine and represents an
      important step toward malaria control and elimination. However, a partially
      effective vaccine such as RTS,S/AS01 poses challenges for evaluating the efficacy
      of second-generation malaria vaccines. Whole-sporozoite immunization approaches
      have shown promising results, inducing sterile immunity in small-scale trials of
      malaria-naive adults, but may not achieve durable sterile protection in endemic
      populations. Vaccines targeting both the pre-erythrocytic and the erythrocyte
      invasive form of the parasite (merozoites) may abrogate breakthrough infections
      by neutralizing merozoites emerging from infected hepatocytes, whereas vaccines
      targeting the sexual stages seek to break the transmission cycle. Moving forward,
      a multi-stage vaccine could be the next step toward malaria elimination and
      eradication.

PMID- 25995986
TI  - Diagnostic accuracy of acyl-ghrelin and it association with non-alcoholic fatty
      liver disease in type 2 diabetic patients.
AB  - BACKGROUND: Ghrelin is a hormone produced mainly by the cells lining the fundus
      of the stomach, which is involved in regulation of lipid and glucose metabolism.
      Two major forms of ghrelin can be found in circulation: an acylated form, and non
      acylated form. Serum acyl-ghrelin (AG) concentration is significantly increased
      in patients with visceral obesity and insulin resistance. This study was
      conducted to evaluate changes in serum AG levels, its diagnostic accuracy and
      association with NAFLD in patients with type two diabetes (T2D). METHODS: In this
      cross-sectional study, 91 T2D patients, age of 40-80 years, were included. All
      patients were divided into 3 groups. The control group included 28 T2D patients
      without NAFLD. The main group included 63 T2D patients with NAFLD, which was
      divided in 2 subgroups depending on transaminase levels: normal (n = 37) and
      elevated (n = 26) transaminases group. To assess the diagnostic accuracy of AG
      for NAFLD we used ROC-analysis. RESULTS: We observed 1.5 (p = 0.016) and 2.5 (p <
      0.001) fold increasing of serum AG levels in patients with NAFLD and normal or
      elevated transaminases compared to control groups. In multivariate logistic
      regression analysis high AG level was an independent, from transaminases
      activity, triglycerides (OR 1.791; 95 % CI 1.162-2.759; p = 0.008) and degree of
      IR (OR 1.599; 95 % CI 1.019-2.508; p = 0.044) predictor that associated with
      NAFLD. When serum AG used as non-invasive marker for NAFLD detection AUROC was
      0.835 (95 % CI 0.752-0.918, p < 0.001). The cut-off value was >0.52 ng/ml, with
      sensitivity, specificity, PPV and NPV - 60.3 %, 92.8 %, 95.0 %, 50.9 %
      respectively. For distinguishing patients with NAFLD and elevated transaminases
      from patients with NAFLD and normal values AG was less effective. CONCLUSIONS:
      Our study has demonstrated that elevated AG level were associated with NAFLD.
      Patients with elevated transaminases had significantly higher AG levels. An
      increase of AG over 0.52 ng/ml can be used as a diagnostic marker for NAFLD
      detection in patients with T2D.

PMID- 25995988
TI  - Population health measurement: applying performance measurement concepts in
      population health settings.
AB  - INTRODUCTION: Whether the focus of population-health improvement efforts, the
      measurement of health outcomes, risk factors, and interventions to improve them
      are central to achieving collective impact in the population health perspective.
      And because of the importance of a shared measurement system, appropriate
      measures can help to ensure the accountability of and ultimately integrate the
      efforts of public health, the health care delivery sector, and other public and
      private entities in the community to improve population health. Yet despite its
      importance, population health measurement efforts in the United States are poorly
      developed and uncoordinated. COLLABORATIVE MEASUREMENT DEVELOPMENT: To achieve
      the potential of the population health perspective, public health officials,
      health system leaders, and others must work together to develop sets of
      population health measures that are suitable for different purposes yet are
      harmonized so that together they can help to improve a community's health. This
      begins with clearly defining the purpose of a set of measures, distinguishing
      between outcomes for which all share responsibility and actions to improve health
      for which the health care sector, public health agencies, and others should be
      held accountable. FRAMEWORK FOR POPULATION HEALTH MEASUREMENT: Depending on the
      purpose of the analysis, then, measurement systems should clearly specify what to
      measure-in particular the population served (the denominator), what the critical
      health dimensions are in a measurement framework, and how the measures can be
      used to ensure accountability. Building on a clear understanding of the purpose
      and dimensions of population health that must be measured, developers can then
      choose specific measures using existing data or developing new data sources if
      necessary, with established validity, reliability, and other scientific
      characteristics. Rather than indiscriminately choosing among the proliferating
      data streams, this systematic approach to measure development can yield
      measurement systems that are more appropriate and useful for improving population
      health.

PMID- 25995987
TI  - An IR Navigation System for Pleural PDT.
AB  - Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with
      lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the
      current pleural PDT protocol, a moving fiber-based point source is used to
      deliver the light. The light fluences at multiple locations are monitored by
      several isotropic detectors placed in the pleural cavity. To improve the delivery
      of light fluence uniformity, an infrared (IR) navigation system is used to track
      the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment
      planning system uses the laser source positions obtained from the IR camera to
      calculate light fluence distribution to monitor the light fluence uniformity on
      the surface of the pleural cavity. A novel reconstruction algorithm is used to
      determine the pleural cavity surface contour. A dual-correction method is used to
      match the calculated fluences at detector locations to the detector readings.
      Preliminary data from a phantom shows superior light uniformity using this
      method. Light fluence uniformity from patient treatments is also shown with and
      without the correction method.

PMID- 25995989
TI  - Creating value: unifying silos into public health business intelligence.
AB  - INTRODUCTION: Through September 2014, federal investments in health information
      technology have been unprecedented, with more than 25 billion dollars in
      incentive funds distributed to eligible hospitals and providers. Over 85 percent
      of eligible United States hospitals and 60 percent of eligible providers have
      used certified electronic health record (EHR) technology and received Meaningful
      Use incentive funds (HITECH Act1). TECHNOLOGY: Certified EHR technology could
      create new public health (PH) value through novel and rapidly evolving data-use
      opportunities, never before experienced by PH. The long-standing "silo" approach
      to funding has fragmented PH programs and departments,2 but the components for
      integrated business intelligence (i.e., tools and applications to help users make
      informed decisions) and maximally reuse data are available now. SYSTEMS:
      Challenges faced by PH agencies on the road to integration are plentiful, but an
      emphasis on PH systems and services research (PHSSR) may identify gaps and
      solutions for the PH community to address. CONCLUSION: Technology and system
      approaches to leverage this information explosion to support a transformed health
      care system and population health are proposed. By optimizing this information
      opportunity, PH can play a greater role in the learning health system.

PMID- 25995990
TI  - Transforming public health systems: using data to drive organizational capacity
      for quality improvement and efficiency.
AB  - INTRODUCTION: This paper examines the organization, services, and priorities of
      public health agencies and their capacity to be learning public health systems
      (LPHS). An LPHS uses data to measure population health and health risks and to
      evaluate its services and programs, and then integrates its own research with
      advances in scientific knowledge to innovate and improve its efficiency and
      effectiveness. PUBLIC HEALTH AGENCIES AND IMPACT FOR LPHS: Public health
      agencies' (PHA) organizational characteristics vary across states, as does their
      funding per capita. Variations in organization, services provided, and
      expenditures per capita may reflect variations in community needs or may be
      associated with unmet needs. The status of legal statutes defining
      responsibilities and authorities and their relationships to other public and
      private agencies also vary. Little information is available on the efficiency and
      effectiveness of state and local PHAs, in part due to a lack of information
      infrastructure to capture uniform data on services provided. There are almost no
      data on the relationship of quality of services, staff performance, and resources
      to population health outcomes. By building a capacity to collect and analyze data
      on population health within and across communities, and by becoming a continuous
      learning PHA, the allocation of resources can more closely match population
      health needs and improve health outcomes. Accreditation of every PHA is an
      important first step toward becoming a learning PHA. CONCLUSIONS: Public Health
      Services and Systems Research (PHSSR) is beginning to shed light on some of these
      issues, particularly by investigating variation across PHAs. As this emerging
      discipline grows, there is a need to enhance the collection and use of data in
      support of building organized, effective, and efficient LPHSs with the PHA
      capacity to continually improve the public's health.

PMID- 25995991
TI  - Developing new systems of data to advance a culture of health.
AB  - INTRODUCTION: The system dynamics that are driving changes in health and health
      care in the United States are not well captured by standard data-collection
      activities. We need data systems that can inform policy and program development
      and can reflect the increasing recognition that all aspects of people's lives
      their work, families, and communities and not just formal health and health care
      services-support active and healthy living. CULTURE OF HEALTH ACTION AREAS:
      Within the Culture of Health (COH) framework, four action areas are further
      upstream in the sequence of change and point to additional need for more nuanced
      approaches to data collection: building a shared value of health; fostering
      collaborations to improve well-being; creating health in more equitable community
      environments; and transforming health and health care systems. These action areas
      define the COH framework that we hope will spur research and strategies across
      sectors to improve health. CONCLUSION: The action framework for advancing a COH
      will guide the Robert Wood Johnson Foundation's (RWJF) grant making and strategic
      collaborations. It is hoped that the framework will also catalyze changes in how
      researchers and organizations collect health-related data at all levels.

PMID- 25995992
TI  - Plakophilin-2 induced EGFR phosphorylation: a focus on the intracellular
      activators of EGFR.
AB  - The oncogenic role of EGFR in many tumors has attracted a great deal of attention
      in the recent years and initiated the development of several potent EGFR
      inhibitors, which are used clinically for cancer treatment. However, the current
      therapeutic inhibition of EGFR signaling is limited to monoclonal antibodies that
      bind to the EGFR extracellular domain or tyrosine kinase inhibitors that block
      EGFR kinase activation directly. Despite the great promise of these inhibitors, a
      certain percentage of patients develop resistance to these therapies,
      highlighting the necessity for alternative therapeutic strategies based on our
      most current knowledge of the mechanisms of EGFR signaling. We recently reported
      that Plakofilin-2 (PKP2) is a novel ligand-independent cytoplasmic activator of
      EGFR signaling. Here we focus on recent studies demonstrating important roles of
      intracellular EGFR activators, and propose targeted disruption of these
      activators as a novel avenue of therapeutic intervention to inhibit EGFR-mediated
      cancer development.

PMID- 25995993
TI  - Novel use of old drug: Anti-rheumatic agent auranofin overcomes imatinib
      resistance of chronic myeloid leukemia cells.
AB  - Patients with chronic myeloid leukemia (CML) are commonly treated with a specific
      inhibitor of BCR-ABL tyrosine kinase, imatinib mesylate (IM). Unfortunately, CML
      patients develop IM-resistance, which has emerged as a significant clinical
      problem. Somatic mutations, especially T315I mutation, in BCR-ABL kinase domain
      represent the most common mechanism underlying drug resistance to tyrosine kinase
      inhibitors (TKI), including imatinib. Thus, it is urgent to develop novel
      therapeutic strategies to overcome TKI-resistance. The anti-rheumatic gold (I)
      compound Auranofin (AF), was recently approved by US Food and Drug Administration
      for Phase II clinical trials to treat leukemia. In a recent study, we discovered
      that AF can selectively inhibit 19S proteasome-associated deubiquitinases (UCHL5
      and USP14), which mediates its anticancer effects. More recently studies we have
      shown that AF inhibits the growth of both Bcr-Abl wild-type cells and IM
      resistant Bcr-Abl-T315I mutation cells in vitro and in vivo. AF-induced Bcr-Abl
      down regulation is associated with diminished mRNA expression and caspase
      dependent Bcr-Abl cleavage. More importantly, we unraveled that AF cytotoxicity
      is mediated by proteasome inhibition rather than previously suspected reactive
      oxygen species (ROS) generation. These findings support that AF overcomes IM
      resistance through Bcr/Abl-dependent and -independent mechanisms, identifying a
      potentially new strategy for cancer treatment.

PMID- 25995994
TI  - Awareness of the association between obesity and peri-operative risk among newly
      diagnosed patients with complex atypical hyperplasia and endometrial cancer.
AB  - OBJECTIVES: To evaluate knowledge of obesity-related peri-operative risks in with
      women newly diagnosed complex atypical hyperplasia and endometrial cancer.
      METHODS: Cross sectional study of patients newly diagnosed with complex atypical
      hyperplasia or endometrial cancer who underwent preoperative counseling between
      2011 and 2014, using a 17-item questionnaire. Obesity was defined as body mass
      index (BMI) of 30 kg/m2 or greater. Bivariate analysis was conducted using
      Pearson's Chi-Square or Fisher's Exact tests where appropriate and Mann-Whitney U
      for continuous variables. RESULTS: Of 98 patients recruited, mean age was 58
      years, 87% were obese, 83% white, and 51% had grade 1 endometrioid
      adenocarcinomas. Sixty-four percent of obese women reported that their physicians
      had discussed surgical risks related to obesity. However, 17% of obese and 42% of
      non-obese patients responded that they were unsure of the peri-operative risks
      associated with obesity. There was substantial lack of understanding among obese
      patients regarding their increased risks of respiratory problems (29%),
      thromboembolism (29%), heart attack (35%), or longer operating time (35%) and
      hospital stay (47%). However, obese patients were more aware of wound infection
      risks associated with obesity compared to their non-obese counterparts (72% vs.
      31%, p=0.004). CONCLUSIONS: Pre-operative counseling for obese women with newly
      diagnosed endometrial cancer should incorporate more focused education about
      obesity-related risks. They report being knowledgeable about the risks associated
      with their surgery, however, more than a quarter are unaware of the impact
      obesity has on respiratory problems, thromboembolism, wound infection, heart
      attack or longer operating time and hospital stay.

PMID- 25995995
TI  - The regulation of the p53/MDM2 feedback loop by microRNAs.
AB  - Tumor suppressor p53 and its signaling pathway play a central role in tumor
      prevention. The E3 ubiquitin ligase MDM2, which is a direct p53 transcriptional
      target and also the most critical negative regulator of p53, forms an
      autoregulatory negative feedback loop with p53 in the cell to tightly regulate
      the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed
      small non-coding RNAs that play a critical role in the post-translational
      regulation of gene expression. Recent studies have revealed that miRNAs directly
      regulate the levels of p53 or MDM2 to modulate the p53 function in tumor
      suppression. Recently, we identified miR-339-5p as a new miRNA that directly
      represses MDM2 to activate p53 and enhance p53 function in tumor suppression.
      Thus, miRNAs have become a new but important component of the p53 signaling
      pathway through regulating the p53/MDM2 feedback loop.

PMID- 25995998
TI  - The unstoppable march of the machines.

PMID- 25995996
TI  - Freeprocessing: Transparent in situ visualization via data interception.
AB  - In situ visualization has become a popular method for avoiding the slowest
      component of many visualization pipelines: reading data from disk. Most previous
      in situ work has focused on achieving visualization scalability on par with
      simulation codes, or on the data movement concerns that become prevalent at
      extreme scales. In this work, we consider in situ analysis with respect to ease
      of use and programmability. We describe an abstraction that opens up new
      applications for in situ visualization, and demonstrate that this abstraction and
      an expanded set of use cases can be realized without a performance cost.

PMID- 25995999
TI  - Carl Djerassi   (1923-2015).

PMID- 25996000
TI  - Howard   Eichenbaum.

PMID- 25996001
TI  - [In process Citation].

PMID- 25996002
TI  - [In Process Citation].

PMID- 25996003
TI  - [In Process Citation].

PMID- 25996004
TI  - [In Process Citation].

PMID- 25996005
TI  - Will NOTES ever become noticed?

PMID- 25996006
TI  - General Surgeons Australia Annual Scientific Meeting: promoting the  future of
      general surgery in Australia.

PMID- 25996007
TI  - Medicine in small doses.

PMID- 25996008
TI  - Surgery of primary tumour has survival benefit in metastatic breast  cancer with
      single-organ metastasis, especially bone.
AB  - BACKGROUND: Surgery for the primary breast tumour is usually not recommended in
      metastatic breast cancer (MBC); however, some reports have suggested a benefit of
      locoregional treatment. We designed this study to evaluate the efficacy of
      locoregional surgery in MBC. METHODS: Data for patients diagnosed with MBC at
      Samsung Medical Center between 1995 and 2011 were retrospectively collected. We
      compared the survival benefit of all treatment modalities using Cox regression
      analysis. Subgroup analyses based on number of metastases were performed to
      delineate the indication for each treatment. RESULTS: Among 262 patients, 40
      (15.3%) underwent surgery. Other treatments included chemotherapy (n = 213,
      81.3%), radiotherapy (n = 138, 52.7%), hormone therapy (n = 118, 45.0%) and
      HER2/neu receptor (HER2)-targeted therapy (n = 37, 14.1%). Cox regression
      analysis showed that surgery (hazard ratios (HR) = 0.51, P < 0.01), hormone
      therapy (HR = 0.31, P < 0.01) and HER2-targeted therapy (HR = 0.33, P < 0.01)
      were associated with improved survival, whereas presence of three or more
      metastatic organs (HR = 1.62, P = 0.03) was associated with poor survival. In
      patients with metastasis to a single organ, surgery (HR = 0.43, P < 0.01),
      chemotherapy (HR = 0.62, P = 0.05), hormone therapy (HR = 0.39, P < 0.01) and
      HER2-targeted therapy (HR = 0.39, P = 0.02) had a survival benefit. Furthermore,
      for patients with bone-only metastasis, surgery (HR = 0.37, P = 0.02),
      chemotherapy (HR = 0.42, P < 0.01), hormone therapy (HR = 0.22, P < 0.01) and
      HER2-targeted therapy (HR = 0.09, P = 0.02) showed a survival benefit. However,
      only hormone therapy and HER2-targeted therapy had a survival benefit in MBC with
      metastasis to multiple organs. CONCLUSION: Surgical control of the primary breast
      tumour should be considered as a locoregional therapy in combination with
      systemic therapy in MBC with metastasis to a single organ, especially bone-only
      metastasis.

PMID- 25996009
TI  - Authors' reply.

PMID- 25996010
TI  - Laser ablation for recurrent intracranial ependymoma.

PMID- 25996011
TI  - Response.

PMID- 25996012
TI  - Periodical shifts in the surgical correction of sagittal craniosynostosis.

PMID- 25996014
TI  - Retraction: Properties and stability of blueberry anthocyanin--bovine serum
      albumin nanoparticles.

PMID- 25996013
TI  - Response.

PMID- 25996028
TI  - Applications of Supramolecular Anion Recognition.

PMID- 25996029
TI  - Bias and Uncertainty in Non-Ideal qNMR Analysis.
AB  - We report a comprehensive analysis of the acquisition-related sources of
      uncertainty for internally and externally standardized qNMR experiments. The
      impacts of major instrument- and sample-related sources of biases and
      uncertainties are quantified where possible, and the validity of correction and
      calibration techniques are also discussed. The application of uncertainty budgets
      for qNMR is well established for simple, internally standardized systems, but the
      model is incomplete and does not allow for the additional biases and sources of
      uncertainty that arise from spectrum complexity and external standardization.
      This report considers the additional contributions to the uncertainty budget that
      need to be considered to ensure SI traceability of measurement across a wider
      range of analytes and NMR methodologies. 

PMID- 25996030
TI  - S-trityl-(R)-cysteine, a multipurpose chiral selector for ligand-exchange liquid
      chromatography applications.
AB  - The stratification of 0.040-0.050 g of S-trityl-(R)-cysteine ((R)-STC) onto a
      conventional ODS phase produces a very effective (alpha and RS up to 5.71 and
      12.09, respectively) and stable (more than 30 days of repeated analysis) chiral
      ligand-exchange chromatography (CLEC) coated chiral stationary phase (C-CSP).
      With a few specific exceptions, a (R) < (S) enantiomer elution order can be
      easily predicted. The (R)-STC-based C-CSP can be successfully exploited also at a
      preparative level for enantioisolations of CNS active amino acids (AAs), with a
      racemate loadability up to 0.015 g for single injection. The CLEC (R)-STC-based
      system can be helpful in monitoring the presence of (R)-AAs in edible products
      and other organic materials, thus contributing to evaluating product quality and
      diagnosing subclinical pathological states in animals and humans. Very
      profitably, molecular modeling-based computer-assisted classification analyses
      can reveal the actual enantioseparation ability of the (R)-STC phase towards a
      specific compound.

PMID- 25996031
TI  - Bioanalytics in Quantitive (Bio)imaging/Mapping of Metallic Elements in
      Biological Samples.
AB  - The aim of this article is to describe selected analytical techniques and their
      applications in the quantitative mapping/(bio)imaging of metals in biological
      samples. This work presents the advantages and disadvantages as well as the
      appropriate methods of scope for research. Distribution of metals in biological
      samples is currently one of the most important issues in physiology, toxicology,
      pharmacology, and other disciplines where functional information about the
      distribution of metals is essential. This issue is a subject of research in
      (bio)imaging/mapping studies, which use a variety of analytical techniques for
      the identification and determination of metallic elements. Increased interest in
      analytical techniques enabling the (bio)imaging of metals in a variety of
      biological material has been observed more recently. Measuring the distribution
      of trace metals in tissues after a drug dose or ingestion of poison-containing
      metals allows for the studying of pathomechanisms and the pathophysiology of
      various diseases and disorders related to the management of metals in human and
      animal systems. 

PMID- 25996033
TI  - A three-arm scaffold carrying affinity molecules for multiplex recognition
      imaging by atomic force microscopy: the synthesis, attachment to silicon tips,
      and detection of proteins.
AB  - We have developed a multiplex imaging method for detection of proteins using
      atomic force microscopy (AFM), which we call multiplex recognition imaging (mRI).
      AFM has been harnessed to identify protein using a tip functionalized with an
      affinity molecule at a single molecule level. However, many events in
      biochemistry require identification of colocated factors simultaneously, and this
      is not possible with only one type of affinity molecule on an AFM tip. To enable
      AFM detection of multiple analytes, we designed a recognition head made from
      conjugating two different affinity molecules to a three-arm linker. When it is
      attached to an AFM tip, the recognition head would allow the affinity molecules
      to function in concert. In the present study, we synthesized two recognition
      heads: one was composed of two nucleic acid aptamers, and the other one composed
      of an aptamer and a cyclic peptide. They were attached to AFM tips through a
      catalyst-free click reaction. Our imaging results show that each affinity unit in
      the recognition head can recognize its respective cognate in an AFM scanning
      process independently and specifically. The AFM method was sensitive, only
      requiring 2 to 3 MUL of protein solution with a concentration of ~2 ng/mL for the
      detection with our current setup. When a mixed sample was deposited on a surface,
      the ratio of proteins could be determined by counting numbers of the analytes.
      Thus, this mRI approach has the potential to be used as a label-free system for
      detection of low-abundance protein biomarkers. 

PMID- 25996034
TI  - Targeted Near-Infrared Fluorescent Turn-on Nanoprobe for Activatable Imaging and
      Effective Phototherapy of Cancer Cells.
AB  - A novel and green multifunctional nanoplatform as a nanocarrier for drug
      delivery, cell imaging, and phototherapy has been engineered. The nanoplatform is
      composed of stabilized carbon spheres (CSs) as cores, a coated polydopamine (PDA)
      shell, targeted folic acid (FA), and the loaded anticancer drug indocyanine green
      (ICG), obtaining CSs@PDA-FA@ICG nanocomposites (NCs). The biocompatible PDA shell
      provided a high fluorescence quenching efficiency and a surface rich in
      functional groups for anchoring FA for targeting cancer cells. Aromatic ICG could
      be effectively loaded into the CSs@PDA-FA system via hydrophobic interactions and
      pi-pi stacking with a loading efficiency of 58.9%. Notably, the activated NIR
      fluorescence in an intracellular environment made CSs@PDA-FA@ICG a sensitive
      "OFF" to "ON" nanoprobe that can be used for NIR imaging. Moreover, compared to
      ICG alone, the CSs@PDA-FA@ICG NCs could induce efficient photoconversion for
      simultaneous synergetic photodynamic therapy (PDT) and photothermal therapy (PTT)
      under a single NIR laser irradiation. The results demonstrated that CSs@PDA
      FA@ICG NCs as a targeted and activated nanoplatform provide new opportunities to
      facilitate the accurate diagnosis of cancer and enhanced treatment efficacy. This
      work stimulates more interest in the design of the facile surface
      functionalization strategy to construct other multifunctional nanocomposites,
      such as nanotubes and nanorods.

PMID- 25996035
TI  - 3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin
      attenuate tactile allodynia in the mouse model of chronic constriction injury.
AB  - PURPOSE: There is a strong medical demand to search for novel, more efficacious
      and safer than available, analgesics for the treatment of neuropathic pain. This
      study investigated antinociceptive activity of intraperitoneally administered 3
      [4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and
      pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in
      mice and evaluated these drugs' influence on motor coordination. In addition,
      microscopic examinations of the sciatic nerve were performed to assess, if a
      surgical method or drug treatment caused changes in the structure of this nerve.
      Moreover, the alterations of nerve growth factor (NGF) content after drug
      treatment were assessed. METHODS: Antiallodynic and antihyperalgesic activities
      of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor
      impairing properties were evaluated in the rotarod test. Microscopic examinations
      of the sciatic nerve were performed using electron microscope. In
      immunohistochemical assays the content of NGF in the sciatic nerve after single
      or repeated administration of test drugs was assessed. RESULTS: Microscopic
      examinations of the sciatic nerve revealed ultrastructural changes in nerve
      fibers indicating for neurodegenerative processes induced by CCI. Seven days
      after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test
      (ED50 values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at
      dose range 0.5-100 mg/kg induced motor deficits in the rotarod test. In
      immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF
      content. CONCLUSIONS: LPP1 has antiallodynic properties and is an interesting
      lead structure in the search for novel analgesics used in neuropathic pain.

PMID- 25996036
TI  - Cytotoxicity effect of graphene oxide on human MDA-MB-231 cells.
AB  - CONTEXT: The use of graphene oxide (GO) in biomedicine and cancer therapy has
      increased significantly owing to its unique physical and chemical properties. As
      a consequence, the toxicity of GO in the environment and in humans has garnered
      more and more attention. OBJECTIVE: In this paper, we studied the potential
      cytotoxicity of GO nanosheets via examining the effect of GO on the viability,
      cellular colony formation and proliferation of a human breast cancer MDA-MB-231
      cell line, which was an ideal model used to study breast disease in vitro.
      METHODS AND RESULTS: The results suggested that higher concentrations of GO
      (>=100 MUg/mL) exhibited time- and dose-dependent cytotoxicity against MDA-MB-231
      cells, suppressed the colony-forming capacity and cellular proliferation.
      Moreover, higher concentrations of GO increased the proportion of G0/G1 phase
      cells and induced the LDH release, as well as the generation of intracellular ROS
      which was also remarkably increased and may directly related with cytotoxicity.
      CONCLUSION: Together, the above results suggested that GO can induce cytotoxicity
      against human breast cancer MDA-MB-231 cells probably due to the cellular ROS
      generation, which providing useful toxicity and mechanism information that can
      help to better inform safety assessments of GO.

PMID- 25996037
TI  - Curcumin attenuates quinocetone-induced oxidative stress and genotoxicity in
      human hepatocyte L02 cells.
AB  - Quinocetone (QCT), a new quinoxaline 1,4-dioxides, has been used as antimicrobial
      feed additive in China. Potential genotoxicity of QCT was concerned as a public
      health problem. This study aimed to investigate the protective effect of curcumin
      on QCT-induced oxidative stress and genotoxicity in human hepatocyte L02 cells.
      Cell viability and intracellular reactive oxygen species (ROS), biomarkers of
      oxidative stress including superoxide dismutase (SOD) activity and glutathione
      (GSH) level were measured. Meanwhile, comet assay and micronucleus assay were
      carried out to evaluate genotoxicity. The results showed that, compared to the
      control group, QCT at the concentration ranges of 2-16 MUg/mL significantly
      decreased L02 cell viability, which was significantly attenuated with curcumin
      pretreatment (2.5 and 5 MUM). In addition, QCT significantly increased cell
      oxidative stress, characterized by increases of intracellular ROS level, while
      decreased endogenous antioxidant biomarkers GSH level and SOD activity (all p <
      0.05 or 0.01). Curcumin pretreatment significantly attenuated ROS formation,
      inhibited the decreases of SOD activity and GSH level. Furthermore, curcumin
      significantly reduced QCT-induced DNA fragments and micronuclei formation. These
      data suggest that curcumin could attenuate QCT-induced cytotoxicity and
      genotoxicity in L02 cells, which may be attributed to ROS scavenging and anti
      oxidative ability of curcumin. Importantly, consumption of curcumin may be a
      plausible way to prevent quinoxaline 1,4-dioxides-mediated oxidative stress and
      genotoxicity in human or animals.

PMID- 25996038
TI  - Zanamivir oral delivery: possibilities revisited.

PMID- 25996039
TI  - The advantages of pulmonary delivery of therapeutic siRNA.

PMID- 25996041
TI  - Buprenorphine: revisiting the efficacy of transdermal delivery system.
AB  - INTRODUCTION: Buprenorphine is a lipid-soluble pharmaceutic used in the
      management of chronic pain. It is a partial agonist at MU-opioid receptors, an
      antagonist at kappa-opioid receptors, an agonist at delta-opioid receptors and a
      partial agonist at ORL-1 (nociceptin) receptors. METHODS: An extensive literature
      search, including Google Scholar and Pubmed database, was conducted. Terms
      including and associated to 'efficacy of transdermal buprenorphine' were utilized
      to procure contemporary research articles in order to evaluate and compare the
      transdermal buprenorphine patch to commonly used traditional pain management
      medications. RESULTS: Transdermal buprenorphine has demonstrated better efficacy
      than conventional pain management pharmacotherapies. Side effects were similar to
      those associated with other opioids and included headache, dizziness, somnolence,
      constipation, dry mouth, nausea, vomiting, pruritus and erythema. Similar to
      transdermal delivery systems used with other medication, transdermal
      buprenorphine was associated with application-site pruritus and application-site
      reactions. CONCLUSION: Transdermal buprenorphine has significant potential for
      managing chronic pain. In addition to increased convenience and efficacy,
      advantages of transdermal buprenorphine include decreased tolerance and decreased
      withdrawal.

PMID- 25996042
TI  - How perifosine affects liposome-encapsulated drug delivery across a cell barrier.
AB  - BACKGROUND: The development of efficient drug delivery systems to transport
      therapeutics across barrier-forming cells remains a challenge. Recently it was
      shown that liposomes containing perifosine, a synthetic analog of
      lysophosphatidylcholine, efficiently deliver liposome encapsulated content across
      barrier-forming cells. METHODS: To elucidate the mechanism of the delivery,
      fluorescent and spin labeled analog of perifosine were synthesized and their
      transport from liposomes to the barrier-forming MDKC cells was measured. RESULTS
      & CONCLUSION: Perifosine analogs are rapidly transported from liposomes into cell
      membranes. The total amount of perifosine accumulated in plasma membranes seems
      to be the most important factor in efficient transepithelial transport of
      liposome-encapsulated substances. Lysolipid-containing liposomal formulations
      seem to be promising candidates as drug delivery systems in general.

PMID- 25996043
TI  - Enhancing nuclear translocation: perspectives in inhaled corticosteroid therapy.
AB  - Corticosteroids are widely used in the treatment of asthma and chronic
      obstructive pulmonary disease (COPD). In contrast to their use in mild-to
      moderate asthma, they are less efficacious in improving lung function and
      controlling the underlying inflammation in COPD. In most clinical trials,
      corticosteroids have shown little benefit in COPD, but have shown a greater
      clinical effect in combination with long-acting bronchodilators. Impaired
      corticosteroid activation of the glucocorticoid receptor (GR) has been reported
      in corticosteroid-insensitive individuals. Reversal of corticosteroid
      insensitivity by enhancing GR nuclear translocation is a potential therapeutic
      target. Preclinical studies suggest members of the nuclear receptor superfamily
      may facilitate glucocorticoid receptor nuclear translocation. Unravelling the
      mechanisms that govern GR nuclear translocation may identify novel therapeutic
      targets for reversing corticosteroid-insensitivity. 

PMID- 25996045
TI  - Nanoformulation strategies for the enhanced oral bioavailability of
      antiretroviral therapeutics.
AB  - The oral delivery of drugs with poor aqueous solubility is challenging and often
      results in poor bioavailability. Various nanoformulation platforms have
      demonstrated improved oral bioavailability of a range of drugs for different
      indications. The focus of this review is to provide an overview of the
      application of nanomedicine to oral antiretroviral therapy and outline how the
      current short-falls of this life-long therapy may be resolved using
      nanotechnology. As well as highlighting the rationale for a nanomedicine-based
      approach, the review focuses on the various strategies used to enhance oral
      bioavailability and describes the mechanisms of particle absorption across the GI
      tract. The recent advances in the development of long-acting formulations for
      both HIV treatment and pre-exposure prophylaxis are also discussed. 

PMID- 25996046
TI  - Cationic cell-penetrating peptides as vehicles for siRNA delivery.
AB  - RNA interference mediated gene silencing has tremendous applicability in fields
      ranging from basic biological research to clinical therapy. However, delivery of
      siRNA across the cell membrane into the cytoplasm, where the RNA silencing
      machinery is located, is a significant hurdle in most primary cells. Cell
      penetrating peptides (CPPs), peptides that possess an intrinsic ability to
      translocate across cell membranes, have been explored as a means to achieve
      cellular delivery of siRNA. Approaches using CPPs by themselves or through
      incorporation into other siRNA delivery platforms have been investigated with the
      intent of improving cytoplasmic delivery. Here, we review the utilization of CPPs
      for siRNA delivery with a focus on strategies developed to enhance cellular
      uptake, endosomal escape and cytoplasmic localization of CPP/siRNA complexes. 

PMID- 25996047
TI  - Cancer cell spheroids for screening of chemotherapeutics and drug-delivery
      systems.
AB  - Over the last few decades, the most popular platform to perform high-throughput
      screening for viable anti-neoplastic compounds has been monolayer cell culture.
      However, cells in monolayer culture lose many of their in vivo characteristics.
      As a result, this platform provides a limited predictive value in determining the
      clinical outcome of the compounds of interest. Using a technique known as 3D
      spheroid culture, may be the answer to this conundrum. Spheroids have been shown
      to mimic the tissue-like properties of tumors necessary for the proper evaluation
      of compounds. In this review, production of cancer cell spheroids, utilization of
      these spheroids in understanding various therapeutic mechanisms and the potential
      for their use in high-throughput screening of drugs and drug-delivery systems are
      discussed in detail. 

PMID- 25996044
TI  - Unlocking the promise of oncolytic virotherapy in glioma: combination with
      chemotherapy to enhance efficacy.
AB  - Malignant glioma is a relentless burden to both patients and clinicians, and
      calls for innovation to overcome the limitations in current management. Glioma
      therapy using viruses has been investigated to accentuate the nature of a virus,
      killing a host tumor cell during its replication. As virus mediated approaches
      progress with promising therapeutic advantages, combination therapy with
      chemotherapy and oncolytic viruses has emerged as a more synergistic and possibly
      efficacious therapy. Here, we will review malignant glioma as well as prior
      experience with oncolytic viruses, chemotherapy and combination of the two,
      examining how the combination can be optimized in the future. 

PMID- 25996048
TI  - Polymersome-based drug-delivery strategies for cancer therapeutics.
AB  - Polymersomes are stable vesicles prepared from amphiphilic polymers and are more
      stable compared with liposomes. Although these nanovesicles have many attractive
      properties for in vitro/in vivo applications, liposome-based drug delivery
      systems are still prevalent in the market. In order to expedite the translational
      potential and to provide medically valuable formulations, the polymersomes need
      to be biocompatible and biodegradable. In this review, recent developments for
      biocompatible and biodegradable polymersomes, including the design of
      intelligent, targeted, and stimuli-responsive vesicles are summarized. 

PMID- 25996052
TI  - Synthesis of Energetic Nitrocarbamates from Polynitro Alcohols and Their
      Potential as High Energetic Oxidizers.
AB  - A new synthesis strategy for the preparation of energetic carbamates and
      nitrocarbamates starting from readily available polynitro alcohols is introduced.
      The efficient synthesis of mainly new carbamates was performed with the reactive
      chlorosulfonyl isocyanate (CSI) reagent. The carbamates were nitrated using mixed
      acid to form the corresponding primary nitrocarbamates. The thermal stability of
      all synthesized compounds was studied using differential scanning calorimetry,
      and the energies of formation were calculated on the CBS-4 M level of theory.
      Detonation parameters and propulsion properties were determined with the software
      package EXPLO5 V6.02. Furthermore, for all new substances single-crystal X-ray
      diffraction studies were performed and are presented and discussed as Supporting
      Information. 

PMID- 25996051
TI  - IL-10 supplementation increases Tregs and decreases hypertension in the RUPP rat
      model of preeclampsia.
AB  - OBJECTIVE: The reduced uterine perfusion pressure (RUPP) rat model of
      preeclampsia was used to determine the effects of added interleukin-10 (IL-10) on
      Tregs and hypertension in response to placental ischemia and how the decrease in
      these anti-inflammatory factors mediates the pathophysiology of preeclampsia.
      METHODS: IL-10 (2.5 ng/kg/d) was infused via osmotic mini-pump implanted
      intraperitoneally on day 14 of gestation and, at the same time, the RUPP
      procedure was performed. RESULTS: IL-10 reduced mean arterial pressure (p <
      0.001), decreased CD4(+) T cells (p = 0.044), while increasing Tregs (p = 0.043)
      which led to lower IL-6 and TNF-alpha (p = 0.008 and p = 0.003), reduced AT1-AA
      production (p < 0.001), and decreased oxidative stress (p = 0.029) in RUPP rats.
      CONCLUSION: These data indicate that IL-10 supplementation increases Tregs and
      helps to balance the altered immune system seen during preeclampsia.

PMID- 25996049
TI  - Exploiting natural anti-tumor immunity for metastatic renal cell carcinoma.
AB  - Clinical observations of spontaneous disease regression in some renal cell
      carcinoma (RCC) patients implicate a role for tumor immunity in controlling this
      disease. Puzzling, however, are findings that high levels of tumor infiltrating
      lymphocytes (TIL) are common to RCC. Despite expression of activation markers by
      TILs, functional impairment of innate and adaptive immune cells has been
      consistently demonstrated contributing to the failure of the immune system to
      control RCC. Immunotherapy can overcome the immunosuppressive effects of the
      tumor and provide an opportunity for long-term disease free survival.
      Unfortunately, complete response rates remain sub-optimal indicating the
      effectiveness of immunotherapy remains limited by tumor-specific factors and/or
      cell types that inhibit antitumor immune responses. Here we discuss
      immunotherapies and the function of multiple immune system components to achieve
      an effective response. Understanding these complex interactions is essential to
      rationally develop novel therapies capable of renewing the immune system's
      ability to respond to these tumors. 

PMID- 25996053
TI  - Crowding measures associated with the quality of emergency department care: a
      systematic review.
AB  - OBJECTIVES: Despite the substantial body of literature on emergency department
      (ED) crowding, to the best of our knowledge, there is no agreement on the measure
      or measures that should be used to quantify crowding. The objective of this
      systematic review was to identify existing measures of ED crowding that have been
      linked to quality of care as defined by the Institute of Medicine (IOM) quality
      domains (safe, effective, patient-centered, efficient, timely, and equitable).
      METHODS: Six major bibliographic databases were searched from January 1980 to
      January 2012, and hand searches were conducted of relevant journals and
      conference proceedings. Observational studies (cross-sectional, cohort, and case
      control), quality improvement studies, quasi-experimental (e.g., before/after)
      studies, and randomized controlled trials were considered for inclusion. Studies
      that did not provide measures of ED crowding were excluded. Studies that did not
      provide quantitative data on the link between crowding measures and quality of
      care were also excluded. Two independent reviewers assessed study eligibility,
      completed data extraction, and assessed study quality using the Newcastle-Ottawa
      Quality Assessment Scale (NOS) for observational studies and a modified version
      of the NOS for cross-sectional studies. RESULTS: The search identified 7,413
      articles. Thirty-two articles were included in the review: six cross-sectional,
      one case-control, 23 cohort, and two retrospective reviews of performance
      improvement data. Methodologic quality was moderate, with weaknesses in the
      reporting of study design and methodology. Overall, 15 of the crowding measures
      studied had quantifiable links to quality of care. The three measures most
      frequently linked to quality of care were the number of patients in the waiting
      room, ED occupancy (percentage of overall ED beds filled), and the number of
      admitted patients in the ED awaiting inpatient beds. None of the articles
      provided data on the link between crowding measures and the IOM domains
      reflecting equitable and efficient care. CONCLUSIONS: The results of this review
      provide data on the association between ED crowding measures and quality of care.
      Three simple crowding measures have been linked to quality of care in multiple
      publications.

PMID- 25996054
TI  - Engineering bioinformatics: building reliability, performance and productivity
      into bioinformatics software.
AB  - There is a lack of software engineering skills in bioinformatic contexts. We
      discuss the consequences of this lack, examine existing explanations and remedies
      to the problem, point out their shortcomings, and propose alternatives. Previous
      analyses of the problem have tended to treat the use of software in scientific
      contexts as categorically different from the general application of software
      engineering in commercial settings. In contrast, we describe bioinformatic
      software engineering as a specialization of general software engineering, and
      examine how it should be practiced. Specifically, we highlight the difference
      between programming and software engineering, list elements of the latter and
      present the results of a survey of bioinformatic practitioners which quantifies
      the extent to which those elements are employed in bioinformatics. We propose
      that the ideal way to bring engineering values into research projects is to bring
      engineers themselves. We identify the role of Bioinformatic Engineer and describe
      how such a role would work within bioinformatic research teams. We conclude by
      recommending an educational emphasis on cross-training software engineers into
      life sciences, and propose research on Domain Specific Languages to facilitate
      collaboration between engineers and bioinformaticians. 

PMID- 25996055
TI  - Direct Visualization of the Hydration Layer on Alumina Nanoparticles with the
      Fluid Cell STEM in situ.
AB  - Rheological behavior of aqueous suspensions containing nanometer-sized powders is
      of relevance to many branches of industry. Unusually high viscosities observed
      for suspensions of nanoparticles compared to those of micron size powders cannot
      be explained by current viscosity models. Formation of so-called hydration layer
      on alumina nanoparticles in water was hypothesized, but never observed
      experimentally. We report here on the direct visualization of aqueous suspensions
      of alumina with the fluid cell in situ. We observe the hydration layer formed
      over the particle aggregates and show that such hydrated aggregates constitute
      new particle assemblies and affect the flow behavior of the suspensions. We
      discuss how these hydrated nanoclusters alter the effective solid content and the
      viscosity of nanostructured suspensions. Our findings elucidate the source of
      high viscosity observed for nanoparticle suspensions and are of direct relevance
      to many industrial sectors including materials, food, cosmetics, pharmaceutical
      among others employing colloidal slurries with nanometer-scale particles. 

PMID- 25996056
TI  - A Qualitative Description of a Family Intervention for Breast Cancer Survivors
      Experiencing Fatigue.
AB  - Breast cancer survivors commonly experience fatigue, but family-focused
      interventions as a means to reduce fatigue are understudied. This qualitative
      study explored the experience of adding a family component to a multimodal group
      intervention for fatigue. Data were collected from group observations, in-depth
      interviews, and debriefing sessions with the program social worker. Fourteen
      survivors completed the family intervention (mean age 57 years) with a family
      member or close friend. Four themes associated with the family intervention were
      identified: (a) importance of family inclusion, (b) education of family members
      about fatigue, 

PMID- 25996057
TI  - Schistosomiasis and its treatment.

PMID- 25996058
TI  - Praziquantel: do we need another antischistosoma treatment?

PMID- 25996059
TI  - Something old, something new: is praziquantel enough for schistosomiasis control?

PMID- 25996060
TI  - How has the genomics era impacted schistosomiasis drug discovery?

PMID- 25996061
TI  - Using an open source model to accelerate schistosomiasis drug research.

PMID- 25996062
TI  - Neglected tropical disease research: rethinking the drug discovery model.

PMID- 25996063
TI  - What is the mechanism of action of praziquantel and how might resistance strike?

PMID- 25996064
TI  - Repurposing apoptosis-inducing cancer drugs to treat schistosomiasis.

PMID- 25996066
TI  - Repurposing pharma assets: an accelerated mechanism for strengthening the
      schistosomiasis drug development pipeline.
AB  - Schistosomiasis, one of 17 diseases deemed to be neglected by the World Health
      Organization, has received little attention from the biopharmaceutical industry.
      Due to this, only a handful of drugs have been developed to treat
      schistosomiasis, with only one, praziquantel, used in most endemic regions.
      Growing concern over resistance coupled with praziquantel's incomplete efficacy
      across all stages of the Schistosoma platyhelminth life cycle highlights the
      urgent need for new drugs. The WIPO Re:Search consortium is a platform whereupon
      biopharmaceutical company compounds are being repurposed to efficiently and cost
      effectively develop new drugs for neglected diseases such as schistosomiasis.
      This article summarizes recent clinical-stage efforts to identify new
      antischistosomals and highlights biopharmaceutical company compounds with
      potential for repurposing to treat schistosomiasis. 

PMID- 25996065
TI  - Design, synthesis and biological evaluation of praziquantel and endoperoxide
      conjugates as antischistosomal agents.
AB  - BACKGROUND: The widespread use of praziquantel for the treatment of
      schistosomiasis has led to concerns over the potential development of drug
      resistance. Therefore, the discovery of novel antischistosomal agents is
      imperative. In this study, a series of praziquantel and endoperoxide conjugates
      were synthesized and evaluated as potential antischistosomal agents. RESULTS:
      Some compounds exhibited high efficacy against both adult and juvenile
      Schistosoma, in in vitro studies. Structure-activity relationship (SAR) analysis
      revealed that compounds with amide bond linker and cyclopentyl adjacent to the
      1,2,4,5-tetraxane pharmacophore displayed the highest efficacy. Overall,
      compounds showed consistent activity against Schistosoma japonicum and
      Schistosoma mansoni. In vivo study resulted in moderate but statistically
      significant activity. CONCLUSION: Important preliminary results were obtained
      from thorough activity evaluation of praziquantel-endoperoxide conjugates.
      Further pharmacokinetic property investigation is necessary to improve in vivo
      efficacy.

PMID- 25996067
TI  - Re-positioning protein-kinase inhibitors against schistosomiasis.
AB  - For decades, Praziquantel (PZQ) is the drug of choice against one of the most
      afflicting helminthic diseases worldwide, schistosomiasis. With respect to the
      fear of upcoming PZQ resistance, efforts are needed to find new chemotherapeutic
      options. Protein kinases (PKs) are essential molecules in signaling processes and
      indispensable to life. Aberrant PK functions take distinctive roles in human
      diseases and represent targets in chemotherapies. In schistosomes, conserved PKs
      were found to possess similar pivotal roles contributing not only to reproduction
      processes, but also to the pathology of schistosomiasis, which is closely
      associated to egg production. Exploiting the similarity of PKs of humans and
      schistosomes, PK inhibitors designed to treat human diseases may serve as lead
      compounds for new drugs against schistosomiasis. 

PMID- 25996068
TI  - Target-based molecular modeling strategies for schistosomiasis drug discovery.
AB  - Schistosomiasis, a neglected tropical disease caused by worms from the class
      Trematoda (genus Schistosoma), is a serious chronic condition that has been
      reported in approximately 80 countries. Nearly 250 million people are affected
      worldwide, mostly in the sub-Saharan Africa. Praziquantel, the mainstay of
      treatment, has been used for 30 years, and cases of resistance have been
      reported. The purpose of this perspective is to discuss current target-based
      molecular modeling strategies in schistosomiasis drug discovery. Advances in the
      field and the role played by the integration between computational modeling and
      experimental validation are also discussed. Finally, recent cases of the
      contribution of modern approaches in computational medicinal chemistry to the
      field are explored. 

PMID- 25996069
TI  - Schistosome sirtuins as drug targets.
AB  - The sirtuins form a superfamily of evolutionarily conserved NAD(+)-dependent
      protein N-epsilon-acyl-lysine (AcK) deacylases with roles in a variety of key
      cellular processes. Sirtuins have a broadly conserved overall structure with a
      catalytic site formed by a hydrophobic channel between the NAD(+)-binding
      Rossmann fold domain and a smaller Zn(2+)-binding domain. Schistosomes express
      five members of the sirtuin family and generic sirtuin inhibitors induce
      apoptosis and death in schistosome larvae, the disruption of adult worm pairs,
      inhibition of egg laying and damage to the male and female worm reproductive
      systems. Sirtuins in schistosomes and other parasitic flatworms present
      structural differences from their human orthologues that should allow the
      development of selective inhibitors that can be developed as drug leads. 

PMID- 25996070
TI  - Drugging the schistosome zinc-dependent HDACs: current progress and future
      perspectives.
AB  - Schistosomes, like many eukaryotic pathogens, typically display morphologically
      distinct stages during their life cycles. Epigenetic mechanisms underlie the
      pathogens' morphological transformations, and the targeting of epigenetics-driven
      cellular programs therefore represents an Achilles' heel of parasites. To speed
      up the search for new antiparasitic agents, drugs validated for other diseases
      can be rationally optimized into antiparasitic therapeutics. Specifically, zinc
      dependent histone deacetylases (HDACs) are the most explored targets for
      epigenetic therapies, notably for anticancer treatments. This review focuses on
      the development of drug-leads inhibiting HDACs from schistosomes. More precisely,
      current progress on Schistosoma mansoni HDAC8 (smHDAC8) provided a proof of
      concept that targeting epigenetic enzymes is a valid approach to treat diseases
      caused by schistosomes, and possibly other eukaryotic pathogens. 

PMID- 25996071
TI  - Natural products with antischistosomal activity.
AB  - In recent years, natural product groups have been gaining prominence as possible
      sources of new drugs for schistosomiasis. This review attempts to update the
      antischistosomal natural compounds, or natural product-derived compounds, from
      the mid-1980s. Some of the main metabolites obtained from plants (e.g., terpenes,
      alkaloids, phenolic compounds and peptides) with in vitro and/or in vivo
      antischistosomal properties are discussed. Less thoroughly, due to scarcity of
      data in the literature, molecules from animals (e.g., peptides) are also
      described. Special mention of the anthelmintic activity against different
      parasitic stages of schistosomes is made; the mechanism of action of most of the
      metabolites is discussed, and a number of bioassay procedures are listed. 

PMID- 25996072
TI  - Toward organometallic antischistosomal drug candidates.
AB  - In the recent years, there has been a growing interest in the use of novel
      approaches for the treatment of parasitic diseases such as schistosomiasis. Among
      the different approaches used, organometallic compounds were found to offer
      unique opportunities in the design of antiparasitic drug candidates. A ferrocenyl
      derivative, namely ferroquine, has even entered clinical trials as a novel
      antimalarial. In this short review, we report on the studies describing the use
      of organometallic compounds against schistosomiasis. 

PMID- 25996073
TI  - Risk factors for non-melanoma skin cancer in patients with essential
      thrombocythemia and polycythemia vera.
AB  - OBJECTIVES: Population-based studies have reported an increased incidence of skin
      cancer in patients with essential thrombocythemia (ET) and polycythemia vera
      (PV). We have examined the risk factors for non-melanoma skin cancer (NMSC) in
      patients diagnosed with ET or PV during 1973-2012. METHODS: A case-control study
      was performed to compare the clinical and treatment-related data of 51 ET/PV
      patients who had NMSC with that of 401 patients who did not. We also evaluated
      whether polymorphisms in 12 genes involved in DNA integrity predisposed to NMSC.
      RESULTS: By multivariate logistic regression analysis, risk factors for NMSC were
      older age (OR: 1.7, 95% CI: 1.3-2.1, P < 0.001), male sex (OR: 2.1, 95% CI: 1.1
      3.8, P = 0.023), higher cumulated hydroxycarbamide dose (OR: 1.3, 95% CI: 1.1
      1.7, P = 0.017), and busulphan exposure (OR: 3.2, 95% CI: 1.05-10.0, P = 0.041).
      On the time-to-event prognostic model, factors independently associated with
      increased cumulative incidence of NMSC were age (5% increased risk per year; P <
      0.001), male sex (91% increased risk; P = 0.022), and hydroxycarbamide exposure
      (22% increased risk; P = 0.065). No susceptibility gene variant was identified.
      CONCLUSIONS: These findings suggest that the risk to develop NMSC in ET/PV
      patients results from the combined effect of common risk factors (age, male sex)
      together with cytoreductive treatment.

PMID- 25996074
TI  - Ambient temperature and risk of first primary basal cell carcinoma: A nationwide
      United States cohort study.
AB  - The Earth's surface is warming and animal studies have shown higher temperatures
      promote ultraviolet radiation (UVR) skin carcinogenesis. There are, however, no
      population studies of long-term temperature exposure and basal cell carcinoma
      (BCC) risk. We linked average lifetime summer ambient temperatures (based on
      weather station data) and satellite-based UVR estimates to self-reported lifetime
      residences in the U.S. Radiologic Technologists' cohort. We assessed the
      relationship between time-dependent average lifetime summer ambient temperature
      (20-year lag) in quintiles and BCC in whites, using Cox proportional hazards
      regression. Risks were adjusted for time-dependent lagged average lifetime UVR
      and time outdoors, body mass index, eye color, and sex (baseline hazard
      stratified on birth cohort). During a median 19.4 years follow-up, we identified
      3556 BCC cases. There was no significant trend in risk between temperature and
      BCC. However, BCC risk was highest in the fourth quintile of temperature (Q4 vs.
      Q1; hazards ratio (HR)=1.18; 95% confidence interval (CI)=1.06-1.31, p
      trend=0.09). BCC risk was strongly related to average lifetime ambient UVR
      exposure (Q5 vs. Q1; HR=1.54 (95% CI=1.35-1.75, p-trend=<0.001)). Future studies
      of temperature and BCC risk should include a broad range of UVR and temperature
      values, along with improved indicators of exposure to temperatures and UVR.

PMID- 25996075
TI  - South African women's conceptualisations of and responses to sexual coercion in
      relation to hegemonic masculinities.
AB  - Despite the documented relationship between hegemonic norms of masculinities and
      South African men's use of sexual violence, less is known about how women's
      engagement with norms of masculinity influences their agency in sexually coercive
      experiences. This study applied a narrative approach to assess how women's
      understandings of hegemonic male norms affected their perceptions of and
      responses to sexually coercive experiences. Twenty-five sexual history narrative
      interviews were conducted with women across five South African provinces
      representing a range of ages, language and sociocultural backgrounds. Interviews
      elicited stories of first experiences of sex and the range of sexual
      relationships through adulthood. Data were analysed using principles of thematic
      and narrative analysis. Coercive sexual experiences informed many women's
      normative ideas about men's sexuality including being impulsive, controlling and
      aggressive. This could underpin women's limited ability to exercise agency and
      their increased vulnerability to sexual abuse. Some women reported levels of
      trust and respect in subsequent relationships, which typically involved
      deconstructing norms of men's use of coercion and moving beyond self-blame and
      guilt. The findings highlight the need to appreciate the fluid and situated
      nature of women's agency from a relational perspective in terms of how women
      condone and challenge gender norms that support men's use of sexual violence in
      their relationships. 

PMID- 25996076
TI  - Ocular manifestations of microcephaly with or without chorioretinopathy,
      lymphedema or intellectual disability (MCLID) syndrome associated with mutations
      in KIF11.
AB  - PURPOSE: Microcephaly with or without chorioretinopathy, lymphedema or
      intellectual disability (MCLID) is an autosomal dominant condition. Mutations in
      KIF11 have been found to be causative in approximately 75% of cases. This study
      describes the ocular phenotype in patients with confirmed KIF11 mutations.
      METHODS: Standard ophthalmic examination and investigation including visual
      acuity, refraction and fundus examination was carried out in all patients. Fundus
      autofluorescence imaging (FAF) was performed in three patients, and four patients
      underwent spectral domain optical coherence tomography (OCT). Flash
      electroretinography (ERG) was performed in seven patients, and five underwent
      additional pattern electroretinography (PERG). RESULTS: The patients ranged in
      age from 2 to 10 years. Most presented with visual acuity loss. Fundus
      examination revealed lacunae of chorioretinal atrophy. Pigmentary macular changes
      and optic disc pallor were present in three of seven patients. Fundus
      autofluorescence demonstrated hypoautofluorescence at the macula in two of three
      patients. The lacunae of chorioretinal atrophy were hypoautofluorescent. The OCT
      showed atrophic maculae in three of four patients. Follow-up in one patient
      showed no deterioration of the vision over a 9-year period. The lesions appear
      not to be progressive on the follow-up imaging. Electrophysiology showed
      generalized rod and cone dysfunction and severe macular dysfunction. Inner
      retinal dysfunction was evident in three of seven patients. CONCLUSIONS: Patients
      with KIF11 mutations show a specific ocular phenotype with variable expressivity
      and intrafamilial variability. Macular atrophy and dysfunction have not been
      consistently documented before. The fundus lesions appear non-progressive. The
      findings assist in providing an accurate diagnosis and thus improving the
      management and follow-up of patients with this syndrome.

PMID- 25996077
TI  - Effect of pulmonary edema on changes in lung mechanics in rats.
AB  - Because of similar pathophysiologic changes, oleic acid (OA)-induced pulmonary
      edema has been well established as an experimental model of certain types of
      ARDS. Data in the literature indicate changes mostly in global pulmonary
      mechanical parameters (lung resistance and compliance) during permeability-type
      edema. Therefore, we designed this study (1) to separate the OA-induced
      mechanical responses into airway and parenchymal components, and (2) to examine
      the relationship between the mechanical parameters and the degree of edema.
      Anaesthetized, paralyzed, mechanically ventilated rats were given iv. OA in doses
      of 0 (C n=9), 0.05 (OA0.05 n=8), 0.1 (OA0.1 n=10) and 0.3 (OA0.3 n=5) ml/kg.
      Respiratory system impedance was measured with a wave-tube low-frequency forced
      oscillation technique, and a model fitting was used to estimate airway (Raw) and
      lung tissue parameters (G, parenchymal damping; H, elastance). Pulmonary edema
      was quantified by gravimetric analysis (WW/DW, wet-to-dry weight ratio). In the
      OAL0.05 group, transient, but significant increase in Raw, only slight increase
      in H, and no response in G was observed. Different responses were obtained in
      OA0.1: significant Raw, G, and H values in survivors; rapid and significantly
      higher responses in all three parameters in non-survivors. Extremely large
      parameter values were measured in OA0.3. We found that OA caused dose-related
      increases in WW, DW and WW/DW. Highly significant correlations were found between
      the degree of edema and G or H, but not Raw. This study demonstrates that low
      dose of OA had only transient lung mechanical effects; however, it resulted in
      mild edema. The higher dose elicited significant airway and tissue changes
      (smaller responses in survivors than in non-survivors), and severe edema. The
      strong correlation between lung tissue parameters and the degree of edema
      suggests that the OA-induced acute lung injury is manifested primarily in the
      alterations in parenchymal mechanics. 

PMID- 25996080
TI  - Non-Ototoxic Local Delivery of Bisphosphonate to the Mammalian Cochlea.
AB  - HYPOTHESIS: Local delivery of bisphosphonates results in superior localization of
      these compounds for the treatment of cochlear otosclerosis, without ototoxicity.
      BACKGROUND: Otosclerosis is a common disorder of abnormal bone remodeling within
      the human otic capsule. It is a frequent cause of conductive hearing loss from
      stapes fixation. Large lesions that penetrate the cochlear endosteum and injure
      the spiral ligament result in sensorineural hearing loss. Nitrogen-containing
      bisphosphonates (e.g., zoledronate) are potent inhibitors of bone remodeling with
      proven efficacy in the treatment of metabolic bone diseases, including
      otosclerosis. Local delivery to the cochlea may allow for improved drug
      targeting, higher local concentrations, and the avoidance of systemic
      complications. In this study, we use a fluorescently labeled bisphosphonate
      compound (6-FAM-ZOL) to determine drug localization and concentration within the
      otic capsule. Various methods for delivery are compared. Ototoxicity is evaluated
      by auditory brainstem responses and distortion product otoacoustic emissions.
      METHODS: 6-FAM-ZOL was administered to guinea pigs via intraperitoneal injection,
      placement of alginate beads onto the round window membrane, or microfluidic pump
      infusion via a cochleostomy. Hearing was evaluated. Specimens were embedded into
      resin blocks, ground to a mid-modiolar section, and quantitatively imaged using
      fluorescence microscopy. RESULTS: There was a dose-dependent increase in
      fluorescent signal after systemic 6-FAM-ZOL treatment. Local delivery via the
      round window membrane or a cochleostomy increased delivery efficiency. No
      significant ototoxicity was observed after either systemic or local 6-FAM-ZOL
      delivery. CONCLUSION: These findings establish important preclinical parameters
      for the treatment of cochlear otosclerosis in humans.

PMID- 25996082
TI  - Synthesis of the Tricyclic Ring Structure of Daphnanes via Intramolecular [4 + 3]
      Cycloaddition/SmI2-Pinacol Coupling.
AB  - A synthetic approach toward the tricyclic 5,7,6-membered ring structure of
      daphnane-family natural products is described. An intramolecular [4 + 3]
      cycloaddition reaction of furan with an oxypentadienyl cation constructed the oxa
      bridged bicyclic structure in a stereoselective fashion. Structural analysis
      revealed that the desired exo isomer was predominantly acquired through
      epimerization. Finally, formation of the five-membered ring was achieved through
      SmI2-mediated pinacol coupling. 

PMID- 25996081
TI  - Osmostress-induced gene expression--a model to understand how stress-activated
      protein kinases (SAPKs) regulate transcription.
AB  - Adaptation is essential for maximizing cell survival and for cell fitness in
      response to sudden changes in the environment. Several aspects of cell physiology
      change during adaptation. Major changes in gene expression are associated with
      cell exposure to environmental changes, and several aspects of mRNA biogenesis
      appear to be targeted by signaling pathways upon stress. Exhaustive reviews have
      been written regarding adaptation to stress and regulation of gene expression. In
      this review, using osmostress in yeast as a prototypical case study, we highlight
      those aspects of regulation of gene induction that are general to various
      environmental stresses as well as mechanistic aspects that are potentially
      conserved from yeast to mammals. 

PMID- 25996083
TI  - Characterization of Novel Ribosome-Associated Endoribonuclease SLFN14 from Rabbit
      Reticulocytes.
AB  - Turnover of mRNA is a critical step that allows cells to control gene expression.
      Endoribonucleases, enzymes cleaving RNA molecules internally, are some of the key
      components of the degradation process. Here we provide a detailed
      characterization of novel endoribonuclease SLFN14 purified from rabbit
      reticulocyte lysate. Schlafen genes encode a family of proteins limited to
      mammals. Their cellular function is unknown or incompletely understood. In
      reticulocytes, SLFN14 is strongly overexpressed, represented exclusively by the
      short form, all tethered to ribosomes, and appears to be one of the major
      ribosome-associated proteins. SLFN14 binds to ribosomes and ribosomal subunits in
      the low part of the body and cleaves RNA but preferentially rRNA and ribosome
      associated mRNA. This results in the degradation of ribosomal subunits. This
      process is strictly Mg(2+)- and Mn(2+)-dependent, NTP-independent, and sequence
      nonspecific. However, in other cell types, SLFN14 is a full-length solely nuclear
      protein, which lacks ribosomal binding and nuclease activities. Mutational
      analysis revealed the ribosomal binding site and the aspartate essential for the
      endonucleolytic activity of protein. Only few endoribonucleases participating in
      ribosome-mediated processes have been characterized to date. Moreover, none of
      them are shown to be directly associated with the ribosome. Therefore, our
      findings expand the general knowledge of endoribonucleases involved in mammalian
      translation control. 

PMID- 25996085
TI  - Vulvar dermatoses: a histopathologic review and classification of 183 cases.
AB  - BACKGROUND: Vulvar dermatoses are often difficult to classify due to
      histopathologic overlap. We aimed to report our experience at a single
      institution. METHODS: A total of 183 non-neoplastic, non-infectious vulvar
      biopsies were reviewed. Associations between histopathologic features and
      specific diagnoses were analyzed by Chi-squared tests. RESULTS: Twenty-two
      biopsies (12.0%) showed two concurrent processes. A limited differential rather
      than a definitive diagnosis was rendered in 15 cases (8.2%). The final diagnoses
      included lichen sclerosus (LS) (38.8%), lichen simplex chronicus (LSC) (29.0%),
      eczematous dermatitis (23.0%), Zoon vulvitis (8.2%), non-specific/resolved
      dermatitis (5.5%), hidradenitis suppurativa (2.7%), Behcet disease (2.2%), lichen
      planus (1.6%), ruptured cyst (1.6%), ulcer not-otherwise-specified (1.6%),
      psoriasis (1.1%), radiation dermatitis (1.1%), sebopsoriasis (1.1%), seborrheic
      dermatitis (1.1%), epidermolytic hyperkeratosis (0.5%) and granular parakeratosis
      (0.5%). Early LS and Zoon vulvitis were commonly included as part of a
      differential diagnosis. LS was associated with wiry collagen with lymphocyte
      entrapment (p = 0.0188). LSC was associated with zones of pale epithelium (p =
      0.0084), and often displayed prominent fibroblasts (p = 0.0555). Zoon vulvitis
      was frequently misdiagnosed, and was associated with basal keratinocytic crowding
      (p < 0.0001). CONCLUSIONS: Our study has determined the relative frequencies of a
      wide variety of vulvar dermatoses, and identified new diagnostic clues for early
      LS, LSC and Zoon vulvitis.

PMID- 25996084
TI  - Efficient generation of monoclonal antibodies from single rhesus macaque antibody
      secreting cells.
AB  - Nonhuman primates (NHPs) are used as a preclinical model for vaccine development,
      and the antibody profiles to experimental vaccines in NHPs can provide critical
      information for both vaccine design and translation to clinical efficacy.
      However, an efficient protocol for generating monoclonal antibodies from single
      antibody secreting cells of NHPs is currently lacking. In this study we
      established a robust protocol for cloning immunoglobulin (IG) variable domain
      genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A
      sorting strategy was developed using a panel of molecular markers (CD3, CD19,
      CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the
      kinetics of B cell response after vaccination. Specific primers for the rhesus
      macaque IG genes were designed and validated using cDNA isolated from macaque
      peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for
      variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335)
      were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV
      subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the
      cloned antibodies. The protocol was tested in a study using an experimental
      dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from
      the vaccinated rhesus macaques react with the dengue vaccine antigens. These
      results validate the protocol for cloning monoclonal antibodies in response to
      vaccination from single macaque antibody secreting cells, which have general
      applicability for determining monoclonal antibody profiles in response to other
      immunogens or vaccine studies of interest in NHPs. 

PMID- 25996087
TI  - E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions.
AB  - BACKGROUND AND AIMS: Aldehydes are emitted by electronic cigarettes due to
      thermal decomposition of liquid components. Although elevated levels have been
      reported with new-generation high-power devices, it is unclear whether they are
      relevant to true exposure of users (vapers) because overheating produces an
      unpleasant taste, called a dry puff, which vapers learn to avoid. The aim was to
      evaluate aldehyde emissions at different power levels associated with normal and
      dry puff conditions. DESIGN: Two customizable atomizers were prepared so that one
      (A1) had a double wick, resulting in high liquid supply and lower chance of
      overheating at high power levels, while the other (A2) was a conventional setup
      (single wick). Experienced vapers took 4-s puffs at 6.5 watts (W), 7.5 W, 9 W and
      10 W power levels with both atomizers and were asked to report whether dry puffs
      were generated. The atomizers were then attached to a smoking machine and aerosol
      was trapped. SETTING: Clinic office and analytical chemistry laboratory in
      Greece. PARTICIPANTS: Seven experienced vapers. MEASUREMENTS: Aldehyde levels
      were measured in the aerosol. FINDINGS: All vapers identified dry puff conditions
      at 9 W and 10 W with A2. A1 did not lead to dry puffs at any power level. Minimal
      amounts of aldehydes per 10 puffs were found at all power levels with A1 (up to
      11.3 ug for formaldehyde, 4.5 ug for acetaldehyde and 1.0 ug for acrolein) and at
      6.5 W and 7.5 W with A2 (up to 3.7 ug for formaldehyde, 0.8 ug for acetaldehyde
      and 1.3 ug for acrolein). The levels were increased by 30 to 250 times in dry
      puff conditions (up to 344.6 ug for formaldehyde, 206.3 ug for acetaldehyde and
      210.4 ug for acrolein, P < 0.001), while acetone was detected only in dry puff
      conditions (up to 22.5 ug). CONCLUSIONS: Electronic cigarettes produce high
      levels of aldehyde only in dry puff conditions, in which the liquid overheats,
      causing a strong unpleasant taste that e-cigarette users detect and avoid. Under
      normal vaping conditions aldehyde emissions are minimal, even in new-generation
      high-power e-cigarettes.

PMID- 25996086
TI  - Meta-analysis reveals the correlation of Notch signaling with non-small cell lung
      cancer progression and prognosis.
AB  - Various studies have assessed the clinicopathological and prognostic value of
      Notch1 and Notch3 expression in Non-small cell lung cancer (NSCLC), but their
      results remain controversial. This meta-analysis was conducted to address the
      above issues by using a total of 19 studies involving 3663 patients. The
      correlations between Notch1 and Notch3 expression and clinicopathological
      features and NSCLC prognosis were analyzed. The meta-analysis indicated that
      higher expression of Notch1 was associated with greater possibility of lymph node
      metastasis and higher TNM stages. Moreover, patients with Notch1 overexpression
      and Notch3 overexpression showed significantly poor overall survival (Notch1: HR,
      1.29; 95% CI, 1.06-1.57, p = 0.468 and I(2) = 0.0%; Notch3: HR, 1.57; 95%CI, 1.04
      2.36, p = 0.445 and I(2) = 0.0%). Furthermore, there are statistically
      significant association between overall survival of NSCLC patients and the
      expression of Notch signaling ligand DLL3 and target gene HES1. Our meta-analysis
      supports that Notch signaling is a valuable bio-marker to predict progression and
      targeting Notch signaling could benefit subpopulation of NSCLC patients.

PMID- 25996088
TI  - Relation of peer effects and school climate to substance use among Asian American
      adolescents.
AB  - Using a nationally representative, longitudinal sample of Asian American late
      adolescents/young adults (ages 18-26), this article investigates the link between
      peer effects, school climate, on the one hand, and substance use, which includes
      tobacco, alcohol, and other illicit mood altering substance. The sample (N =
      1585) is drawn from the National Longitudinal Study of Adolescent Health (Waves I
      and III). The study is set to empirically test premises of generational, social
      capital and stage-environment fit theories. The exploratory variables include
      individual-level (immigrant generation status, ethnic origin, co-ethnic and co
      generational peers - peers from the same immigrant generation) as well as school
      level measures (average school socio-economic status and school climate).
      Multilevel modeling (logistic and negative binomial regression) was used to
      estimate substance use. Results indicate that preference for co-generational
      friends is inversely associated with frequency of cannabis and other illicit drug
      use and preference for co-ethnic peers is inversely associated with other illicit
      drug use. We also find that school climate is a strong and negative predictor of
      frequency of cannabis and other illicit drug use as well as of heavy episodic
      drinking. In terms of policy, these findings suggest that Asian American students
      should benefit from co-ethnic and co-generational peer networks in schools and,
      above all, from improving school climate. 

PMID- 25996089
TI  - Concurrent validity of Zimbardo Time Perspective Inventory profiles: A secondary
      analysis of data from the United Kingdom.
AB  - This paper examined the association between membership in profiles based on a
      shortened form of the Zimbardo Time Perspective Inventory (ZTPI-S; McKay,
      Andretta, McGee, & Worrell, 2014) and other temporal and psychosocial variables.
      Participants consisted of 1620 adolescents attending high school in Northern
      Ireland. ZTPI-S scores had correlations with other temporal and psychosocial
      variables that were similar to those reported for ZTPI scores in previous
      studies. Four ZTPI-S profiles were identified-Balanced, Past Negative, Present
      Hedonistic, and Future-and results indicated that these profiles had
      theoretically meaningful relationships with self-esteem, self-efficacy,
      aggression, parental attachment, consideration of future consequences, and future
      temporal focus. Unlike studies of college students where the Balanced profile was
      related to more adaptive functioning, the Future profile was related to more
      adaptive functioning. Future studies are needed to establish the generalizability
      of these profiles and to determine if there are developmental differences in
      which profiles are more adaptive. 

PMID- 25996091
TI  - Expedited Record Base Fabrication Using an Irreversible Hydrocolloid Cast.
AB  - The registration of a maxillomandibular relationship requires additional clinical
      and laboratory procedures when the mouth presents with loss of occlusal support.
      This procedure can be a challenge for a patient who needs urgent care or resides
      in a remote area. This article describes a procedure for expediting the mounting
      of a master cast for the fabrication of a maxillary immediate complete denture.
      The technique presented describes the use of a silicone record base made on an
      irreversible hydrocolloid cast generated from the final impression. 

PMID- 25996092
TI  - Geographic disparity of severe vision loss - United States, 2009-2013.
AB  - Vision loss and blindness are among the top 10 disabilities in the United States,
      causing substantial social, economic, and psychological effects, including
      increased morbidity, increased mortality, and decreased quality of life.* There
      are disparities in vision loss based on age, sex, race/ethnicity, socioeconomic
      status, and geographic location. Current surveillance activities using national
      and state surveys have characterized vision loss at national and state levels.
      However, there are limited data and research at local levels, where interventions
      and policy decisions to reduce the burden of vision loss and eliminate
      disparities are often developed and implemented. CDC analyzed data from the
      American Community Survey (ACS) to estimate county-level prevalence of severe
      vision loss (SVL) (being blind or having serious difficulty seeing even when
      wearing glasses) in the United States and to describe its geographic pattern and
      its association with poverty level. Distinct geographic patterns of SVL
      prevalence were found in the United States; 77.3% of counties in the top SVL
      prevalence quartile (>=4.2%) were located in the South. SVL was significantly
      correlated with poverty (r = 0.5); 437 counties were in the top quartiles for
      both SVL and poverty, and 83.1% of those counties were located in southern
      states. A better understanding of the underlying barriers and facilitators of
      access and use of eye care services at the local level is needed to enable the
      development of more effective interventions and policies, and to help planners
      and practitioners serve the growing population with and at risk for vision loss
      more efficiently. 

PMID- 25996093
TI  - Fatal and nonfatal drowning outcomes related to dangerous underwater breath
      holding behaviors - New York State, 1988-2011.
AB  - Drowning is an important cause of preventable injury and mortality, ranking fifth
      among leading causes of unintentional injury death in the United States. In 2011,
      two healthy young men died in a drowning incident at a New York City (NYC)
      regulated swimming facility. The men became unconscious underwater after
      performing intentional hyperventilation before submersion. The phenomenon of
      healthy swimmers becoming unconscious underwater has been described elsewhere as
      hypoxic blackout. Prompted by this incident, the NYC Department of Health and
      Mental Hygiene (DOHMH) in collaboration with the New York State Department of
      Health (SDOH) conducted a case review of New York state fatal and nonfatal
      drownings reported during 1988-2011 to investigate similar behaviors in other
      incidents. DOHMH identified 16 cases, three in NYC, with a consistent set of
      voluntary behaviors associated with unintentional drowning and designated this
      class of behaviors as "dangerous underwater breath-holding behaviors" (DUBBs).
      For this small sample, the frequency of different DUBBs varied by age and
      swimming level, and practicing more than one DUBB increased the risk for
      fatality. This research contributes to the literature on drowning by focusing on
      contributing behaviors rather than drowning outcomes. NYC recently enacted public
      health education and regulations that discourage DUBBs; these interventions have
      the potential to effectively reduce unintentional drowning related to these
      behaviors and could be considered by other municipalities and jurisdictions. 

PMID- 25996094
TI  - Tetanus, diphtheria, pertussis vaccination coverage before, during, and after
      pregnancy - 16 States and New York City, 2011.
AB  - In June 2011, the Advisory Committee on Immunizations Practices (ACIP)
      recommended 1 dose of a tetanus, diphtheria, and acellular pertussis (Tdap)
      vaccine during pregnancy for women who had not received Tdap previously. Before
      2011, Tdap was recommended for unvaccinated women either before pregnancy or
      postpartum. In October 2012, ACIP expanded the 2011 recommendation, advising
      pregnant women to be vaccinated with Tdap during each pregnancy to provide
      maternal antibodies for each infant. The optimal time for vaccination is at 27-36
      weeks' gestation as recommended by ACIP. In response to ACIP's Tdap
      recommendation for pregnant women in 2011, CDC added a supplemental question to
      the Pregnancy Risk Assessment Monitoring System (PRAMS) survey to determine
      women's Tdap vaccination status before, during, or after their most recent
      delivery. This report describes overall and state-specific Tdap vaccination
      coverage around the time of pregnancy using data from 6,852 sampled women who
      delivered a live-born infant during September-December 2011 in one of 16 states
      or New York City (NYC). Among the 17 jurisdictions, the median percentage of
      women with live births who reported any Tdap vaccination was 55.7%, ranging from
      38.2% in NYC to 76.6% in Nebraska. The median percentage who received Tdap before
      pregnancy was 13.9% (range = 7.7%-20.1%), during pregnancy was 9.8% (range = 3.8%
      14.2%), and after delivery was 30.9% (range = 13.6%-46.5%). The PRAMS data
      indicate a wide variation in Tdap vaccination coverage among demographic groups,
      with generally higher postpartum coverage for non-Hispanic white women, those who
      started prenatal care in the first trimester, and those who had private health
      insurance coverage. This information can be used for promoting evidence-based
      strategies to communicate the importance of ACIP guidelines related to Tdap
      vaccination coverage to women and their prenatal care providers. 

PMID- 25996095
TI  - Progress toward polio eradication - worldwide, 2014-2015.
AB  - In 1988, the World Health Assembly of the World Health Organization (WHO)
      resolved to eradicate polio worldwide. Wild poliovirus (WPV) transmission has
      been interrupted in all but three countries (Afghanistan, Nigeria, and Pakistan).
      No WPV type 2 cases have been detected worldwide since 1999, and the last WPV
      type 3 case was detected in Nigeria in November 2012; since 2012, only WPV type 1
      has been detected. Circulating vaccine-derived poliovirus (cVDPV), usually type
      2, continues to cause cases of paralytic polio in communities with low population
      immunity. In 2012, the World Health Assembly declared global polio eradication "a
      programmatic emergency for global public health", and in 2014, WHO declared the
      international spread of WPV to previously polio-free countries to be "a public
      health emergency of international concern". This report summarizes global
      progress toward polio eradication during 2014-2015 and updates previous reports.
      In 2014, a total of 359 WPV cases were reported in nine countries worldwide.
      Although reported WPV cases increased in Pakistan and Afghanistan, cases in
      Nigeria decreased substantially in 2014, and encouraging progress toward global
      WPV transmission interruption has occurred. Overcoming ongoing challenges to
      interruption of WPV transmission globally will require sustained programmatic
      enhancements, including improving the quality of supplementary immunization
      activities (SIAs) to interrupt transmission in Afghanistan and Pakistan and to
      prevent WPV exportation to polio-free countries. 

PMID- 25996096
TI  - State-specific prevalence of current cigarette smoking and smokeless tobacco use
      among adults aged >=18 years - United States, 2011-2013.
AB  - Cigarette smoking and the use of smokeless tobacco both cause substantial
      morbidity and premature mortality. The concurrent use of these products might
      increase dependence and the risk for tobacco-related disease and death. State
      specific estimates of prevalence and relative percent change in current cigarette
      smoking, smokeless tobacco use, and concurrent cigarette smoking and smokeless
      tobacco use among U.S. adults during 2011-2013, developed using data from the
      Behavioral Risk Factor Surveillance System (BRFSS), indicate statistically
      significant (p<0.05) changes for all three behaviors. From 2011 to 2013, there
      was a statistically significant decline in current cigarette smoking prevalence
      overall and in 26 states. During the same period, use of smokeless tobacco
      significantly increased in four states: Louisiana, Montana, South Carolina, and
      West Virginia; significant declines were observed in two states: Ohio and
      Tennessee. In addition, the use of smokeless tobacco among cigarette smokers
      (concurrent use) significantly increased in five states (Delaware, Idaho, Nevada,
      New Mexico, and West Virginia). Although annual decreases in overall cigarette
      smoking among adults in the United States have occurred in recent years, there is
      much variability in prevalence of cigarette smoking, smokeless tobacco, and
      concurrent use across states. In 2013, the prevalence ranged from 10.3% (Utah) to
      27.3% (West Virginia) for cigarette smoking; 1.5% (District of Columbia and
      Massachusetts) to 9.4% (West Virginia) for smokeless tobacco; and 3.1% (Vermont)
      to 13.5% (Idaho) for concurrent use. These findings highlight the importance of
      sustained comprehensive state tobacco-control programs funded at CDC-recommended
      levels, which can accelerate progress toward reducing tobacco-related disease and
      deaths by promoting evidence-based population-level interventions. These
      interventions include increasing the price of tobacco products, implementing
      comprehensive smoke-free laws, restricting tobacco advertising and promotion,
      controlling access to tobacco products, and promoting cessation assistance for
      smokers to quit, as well as continuing and implementing mass media campaigns that
      contain graphic anti-smoking ads, such as the Tips from Former Smokers (TIPS)
      campaign. 

PMID- 25996097
TI  - Notes from the field: hepatitis E outbreak among refugees from South Sudan -
      Gambella, Ethiopia, April 2014-January 2015.
AB  - In early April 2014, two South Sudanese refugees in the Gambella region of
      western Ethiopia experienced acute onset of jaundice, accompanied by fever. One
      patient was a pregnant woman aged 24 years evaluated at a routine prenatal clinic
      visit in Leitchour refugee camp. The second patient was a malnourished boy aged 1
      year who resided in Tierkidi refugee camp. The boy died despite hospitalization.
      During the last 2 weeks of May, four more cases of acute jaundice syndrome (AJS),
      defined as yellow discoloration of the eyes, were detected in Leitchuor. By mid
      June, an additional 50 AJS cases were reported across three large camps in the
      region, Kule, Leitchuor, and Tierkidi, with 45 (90%) of these cases reported in
      Leitchuor. Sera collected from a convenience sample of 21 AJS cases were sent to
      Addis Ababa and Nairobi for real-time polymerase chain reaction testing; 12 (57%)
      were positive for hepatitis E virus (HEV) RNA. By January 2015, a total of 1,117
      suspected cases of hepatitis E meeting the case definition of AJS were reported
      among refugees in camps across Gambella. 

PMID- 25996098
TI  - Spatiotemporal Control of Electrokinetic Transport in Nanofluidics Using an
      Inverted Electron-Beam Lithography System.
AB  - Manipulation techniques of biomolecules have been proposed for biochemical
      analysis which combine electrokinetic dynamics, such as electrophoresis or
      electroosmotic flow, with optical manipulation to provide high throughput and
      high spatial degrees of freedom. However, there are still challenging problems in
      nanoscale manipulation due to the diffraction limit of optics. We propose here a
      new manipulation technique for spatiotemporal control of chemical transport in
      nanofluids using an inverted electron-beam (EB) lithography system for liquid
      samples. By irradiating a 2.5 keV EB to a liquid sample through a 100-nm-thick
      SiN membrane, negative charges can be generated within the SiN membrane, and
      these negative charges can induce a highly focused electric field in the liquid
      sample. We showed that the EB-induced negative charges could induce fluid flow,
      which was strong enough to manipulate 240 nm nanoparticles in water, and we
      verified that the main dynamics of this EB-induced fluid flow was electroosmosis
      caused by changing the zeta potential of the SiN membrane surface. Moreover, we
      demonstrated manipulation of a single nanoparticle and concentration patterning
      of nanoparticles by scanning EB. Considering the shortness of the EB wavelength
      and Debye length in buffer solutions, we expect that our manipulation technique
      will be applied to nanomanipulation of biomolecules in biochemical analysis and
      control. 

PMID- 25996099
TI  - Bioactive Metabolites from Mangrove Endophytic Fungus Aspergillus sp. 16-5B.
AB  - Chemical investigation of the endophytic fungus Aspergillus sp. 16-5B cultured on
      Czapek's medium led to the isolation of four new metabolites, aspergifuranone
      (1), isocoumarin derivatives (+/-) 2 and (+/-) 3, and (R)-3-demethylpurpurester A
      (4), together with the known purpurester B (5) and pestaphthalides A (6). Their
      structures were determined by analysis of 1D and 2D NMR spectroscopic data. The
      absolute configuration of Compound 1 was determined by comparison of the
      experimental and calculated electronic circular dichroism (ECD) spectra, and that
      of Compound 4 was revealed by comparing its optical rotation data and CD with
      those of the literature. The structure of Compound 6 was further confirmed by
      single-crystal X-ray diffraction experiment using CuKalpha radiation. All
      isolated compounds were evaluated for their alpha-glucosidase inhibitory
      activities, and Compound 1 showed significant inhibitory activity with IC50 value
      of 9.05 +/- 0.60 MUM. Kinetic analysis showed that Compound 1 was a
      noncompetitive inhibitor of alpha-glucosidase. Compounds 2 and 6 exhibited
      moderate inhibitory activities. 

PMID- 25996100
TI  - Capgermacrenes A and B, Bioactive Secondary Metabolites from a Bornean Soft
      Coral, Capnella sp.
AB  - Two new bicyclogermacrenes, capgermacrenes A (1) and B (2), were isolated with
      two known compounds, palustrol (3) and litseagermacrane (4), from a population of
      Bornean soft coral Capnella sp. The structures of these metabolites were
      elucidated based on spectroscopic data. Compound 1 was found to inhibit the
      accumulation of the LPS-induced pro-inflammatory IL-1b and NO production by down
      regulating the expression of iNOS protein in RAW 264.7 macrophages. 

PMID- 25996101
TI  - Concurrent Neoadjuvant Chemoradiotherapy for Siewert II and III Adenocarcinoma at
      Gastroesophageal Junction.
AB  - OBJECTIVE: This study was conducted to investigate the efficacy and safety of
      using a concurrent neoadjuvant chemoradiotherapy (a XELOX regimen) to treat
      adenocarcinoma of the gastroesophageal junction. METHODS: Seventy-six patients
      having resectable adenocarcinoma at the gastroesophageal junction (T3/4, N+, M0)
      were recruited to participate and randomly assigned to either a chemoradiotherapy
      group or a surgery group. Patients in the chemoradiotherapy group were orally
      given capecitabine (1,000 mg/m2, twice daily for 14 days, days 1-14) and
      intravenous oxaliplatin (130 mg/m2 on day 1) for 2 cycles. Radiotherapy was
      performed with a total of 45 Gy administered in 25 sessions for 5 weeks. Patients
      in the surgery group received only surgical intervention. RESULTS: In the
      concurrent chemoradiotherapy group, the overall response rate was 55.6% (20/36),
      tumor control rate was 100% and a pathological complete response was achieved in
      16.7% (6/36). The entire chemoradiotherapy group had R0 resections as did 80% of
      the surgery group (32/40) (P < 0.05). In the concurrent chemoradiotherapy group,
      6 patients developed grade 3 side effects. Treatment was either discontinued or
      the dose adjusted. Major hematological side effects in the chemoradiotherapy
      group included leukopenia, neutropenia, anemia and thrombocytopenia.
      Nonhematological side effects included nausea, vomiting and appetite loss.
      Chemoradiotherapy-related death was not observed. CONCLUSIONS: Concurrent
      neoadjuvant chemoradiotherapy administration increased the rate of R0 resection
      and demonstrated favorable safety in patients with Siewert II or III
      adenocarcinoma at the gastroesophageal junction. These results support the use of
      neoadjunctive chemoradiotherapy in the treatment of adenocarcinoma of the
      gastroesophageal junction.

PMID- 25996103
TI  - A reciprocal effects model of the temporal ordering of basic psychological needs
      and motivation.
AB  - Using self-determination theory as the framework, we examined the temporal
      ordering between satisfaction and thwarting of basic psychological needs and
      motivation. We accomplished this goal by using a two-wave 7-month partial least
      squares path modeling approach (PLS-PM) among a sample of 94 adolescent athletes
      (Mage = 15.96) in an intensive training setting. The PLS-PM results showed
      significant paths leading: (a) from T1 satisfaction of basic psychological need
      for competence to T2 identified regulation, (b) from T1 external regulation to T2
      thwarting and satisfaction of basic psychological need for competence, and (c)
      from T1 amotivation to T2 satisfaction of basic psychological need for
      relatedness. Overall, our results suggest that the relationship between basic
      psychological need and motivation varied depending on the type of basic need and
      motivation assessed. Basic psychological need for competence predicted identified
      regulation over time whereas amotivation and external regulation predicted basic
      psychological need for relatedness or competence over time. 

PMID- 25996102
TI  - Stress-related biomarkers in dogs administered regional anaesthesia or fentanyl
      for analgesia during stifle surgery.
AB  - OBJECTIVES: To compare the effects of regional anaesthesia and opioid
      administration on adrenocortical and glycaemic responses, postoperative pain and
      recovery quality in dogs undergoing stifle surgery. STUDY DESIGN: Prospective,
      blinded clinical study. ANIMALS: Forty-five dogs anaesthetized for tibial
      tuberosity advancement or tibial plateau levelling osteotomy, and 15 healthy dogs
      undergoing non-invasive orthopaedic diagnostic procedures. METHODS: The baseline
      behaviour of each dog was classified on a descriptive scale before anaesthesia.
      Dogs were anaesthetized using a standard protocol. Those undergoing surgery were
      randomly assigned to one of three intraoperative analgesia protocols: 1)
      peripheral (femoral and sciatic) nerve block (bupivacaine 0.5%; 0.15 mL kg(-1) in
      each nerve; group PNB); 2) spinal anaesthesia (isobaric bupivacaine 0.5%; 0.05 mL
      kg(-1); group SPI); and 3) intravenous fentanyl variable rate infusion and
      postoperative methadone (0.2 mg kg(-1); group FEN). Blood samples were collected
      for measurement of cortisol and glucose concentrations on arrival (TAR), at
      induction (TIND), at tracheal extubation (TEXT), and 1 hour post-extubation
      (TPEX). After extubation, a researcher unaware of the dog's group assignment
      evaluated pain and recovery quality using the Glasgow Composite Measure Pain
      Scale (Short-Form) and a descriptive scale, respectively. RESULTS: Median
      recovery quality was significantly worse in group FEN (p < 0.0001) compared with
      all other groups. Postoperative pain scores were lower in group PNB compared with
      groups SPI and FEN. Cortisol and glucose concentrations increased significantly
      from TAR at TEXT and TPEX (p < 0.0001) in group FEN, and were unchanged from TAR
      in the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Analgesia with a
      peripheral nerve block or spinal anaesthesia prevented the glycaemic and cortisol
      responses to surgery, promoted better recovery quality, and decreased
      postoperative pain scores compared with FEN. In the present study, the regional
      anaesthesia techniques used were found to be excellent alternatives to fentanyl
      administration.

PMID- 25996104
TI  - Ego depletion and attention regulation under pressure: is a temporary loss of
      self-control strength indeed related to impaired attention regulation?
AB  - In the current study we investigated whether ego depletion negatively affects
      attention regulation under pressure in sports by assessing participants' dart
      throwing performance and accompanying gaze behavior. According to the strength
      model of self-control, the most important aspect of self-control is attention
      regulation. Because higher levels of state anxiety are associated with impaired
      attention regulation, we chose a mixed design with ego depletion (yes vs. no) as
      between-subjects and anxiety level (high vs. low) as within-subjects factor.
      Participants performed a perceptual-motor task requiring selective attention,
      namely, dart throwing. In line with our expectations, depleted participants in
      the high-anxiety condition performed worse and displayed a shorter final fixation
      on bull's eye, demonstrating that when one's self-control strength is depleted,
      attention regulation under pressure cannot be maintained. This is the first study
      that directly supports the general assumption that ego depletion is a major
      factor in influencing attention regulation under pressure. 

PMID- 25996105
TI  - Affective and Enjoyment Responses to High-Intensity Interval Training in
      Overweight-to-Obese and Insufficiently Active Adults.
AB  - High-intensity interval training (HIIT) has many known physiological benefits,
      but research investigating the psychological aspects of this training is limited.
      The purpose of the current study is to investigate the affective and enjoyment
      responses to continuous and high-intensity interval exercise sessions. Twenty
      overweight-to-obese, insufficiently active adults completed four counterbalanced
      trials: a 20-min trial of heavy continuous exercise and three 24-min HIIT trials
      that used 30-s, 60-s, and 120-s intervals. Affect declined during all trials (p <
      .05), but affect at the completion of trials was more positive in the shorter
      interval trials (p < .05). Enjoyment declined in the 120-s interval and heavy
      continuous conditions only (p < .05). Postexercise enjoyment was higher in the 60
      s trial than in the 120-s trial and heavy continuous condition (p < .05).
      Findings suggest that pleasure and enjoyment are higher during shorter interval
      trials than during a longer interval or heavy continuous exercise. 

PMID- 25996106
TI  - Physical self-concept changes in a selective sport high school: a longitudinal
      cohort-sequence analysis of the big-fish-little-pond effect.
AB  - Elite athletes and nonathletes (N = 1,268) attending the same selective sport
      high school (4 high school age cohorts, grades 7-10, mean ages varying from 10.9
      to 14.1) completed the same physical self-concept instrument 4 times over a 2
      year period (multiple waves). We introduce a latent cohort-sequence analysis that
      provides a stronger basis for assessing developmental stability/change than
      either cross-sectional (multicohort, single occasion) or longitudinal (single
      cohort, multiple occasion) designs, allowing us to evaluate latent means across
      10 waves spanning a 5-year period (grades 7-11), although each participant
      contributed data for only 4 waves, spanning 2 of the 5 years. Consistent with the
      frame-of-reference effects embodied in the big-fish-little-pond effect (BFLPE),
      physical self-concepts at the start of high school were much higher for elite
      athletes than for nonathlete classmates, but the differences declined over time
      so that by the end of high school there were no differences in the 2 groups.
      Gender differences in favor of males had a negative linear and quadratic
      trajectory over time, but the consistently smaller gender differences for
      athletes than for nonathletes did not vary with time. 

PMID- 25996107
TI  - Antisocial sport behaviors survey: instrument development and initial validation.
AB  - The development of a self-report instrument to measure antisocial sport behavior,
      labeled the Antisocial Sport Behavior Survey (ASBS), among large and diverse
      samples of athletes is reported. Grounded in the social cognitive theory of moral
      thought and action (Bandura, 1991) and interpersonal theory (Horowitz, 2004),
      this instrument was developed and tested in accordance with the traditions of
      construct validity and classical test theory (Gehlback & Brinkworth, 2011). In
      Phase 1, 272 college-aged competitive sport participants confirmed a theoretical
      structure of antisocial sport behavior including eight factors (hypercompetitive,
      intimidating, antagonistic, disrespectful, exploitable, overly accommodating,
      abetting, and melodramatic). Phase 2 reports on item development and the response
      structure of the instrument. In Phase 3, evidence of structural validity and
      external validity for the ASBS was established with 340 college-aged competitive
      sport participants. The ASBS presents as a promising new instrument to advance
      understanding of antisocial sport behavior acts committed by competitive
      athletes. 

PMID- 25996108
TI  - The relationship between meeting vigorous physical activity recommendations and
      burnout symptoms among adolescents: an exploratory study with vocational
      students.
AB  - This study examines how students who met the current recommendations for vigorous
      physical activity (VPA) of the American College of Sports Medicine (ACSM) and the
      Centers of Disease Control and Prevention (CDC) differ from peers who did not
      reach these standards with regard to self-reported burnout, before and after
      controlling for light physical activity and moderate physical activity. A sample
      of 144 vocational students (Mage =16.2 years, SD = 1.13, 98 males) completed the
      International Physical Activity Questionnaire, the Shirom-Melamed Burnout
      Measure, and the School Burnout Inventory. Bivariate correlations revealed that
      only VPA was associated with reduced burnout. Both the ACSM and CDC guidelines
      were useful to identify significant differences in burnout symptoms between
      students who met versus did not meet the standards. Health policy makers should
      develop strategies to integrate more VPA into the lives of adolescent students so
      as to reach a minimum of 60 min per week. 

PMID- 25996109
TI  - Relationships between the coach-created motivational climate and athlete
      engagement in youth sport.
AB  - Youth sport is a source of well-being for adolescents, yet experiences vary and
      attrition can be high. We sought to better understand the coach behaviors that
      foster positive experiences in youth sport by examining relationships between the
      motivational climate and athlete engagement (viz., confidence, dedication,
      enthusiasm, and vigor). We reasoned that a mastery climate (emphasis on effort
      and learning) would correspond with higher engagement, whereas a performance
      climate (emphasis on ability and outcome) was expected to correspond with lower
      engagement. Two-hundred sixty adolescent soccer players completed measures of
      engagement and perceived coach motivational climate. All dimensions of engagement
      were positively predicted by a mastery climate. Furthermore, cognitive aspects of
      engagement were positively predicted by a performance climate. Canonical
      correlation analysis indicated that a composite of engagement was positively
      associated with a mastery climate. Results suggest that a mastery climate offers
      a means of promoting higher levels of overall engagement. 

PMID- 25996111
TI  - The effect of uniform color on judging athletes' aggressiveness, fairness, and
      chance of winning.
AB  - In the current study we questioned the impact of uniform color in boxing,
      taekwondo and wrestling. On 18 photos showing two athletes competing, the hue of
      each uniform was modified to blue, green or red. For each photo, six color
      conditions were generated (blue-red, blue-green, green-red and vice versa). In
      three experiments these 108 photos were randomly presented. Participants (N =
      210) had to select the athlete that seemed to be more aggressive, fairer or more
      likely to win the fight. Results revealed that athletes wearing red in boxing and
      wrestling were judged more aggressive and more likely to win than athletes
      wearing blue or green uniforms. In addition, athletes wearing green were judged
      fairer in boxing and wrestling than athletes wearing red. In taekwondo we did not
      find any significant impact of uniform color. Results suggest that uniform color
      in combat sports carries specific meanings that affect others' judgments. 

PMID- 25996110
TI  - Self-control, self-regulation, and doping in sport: a test of the strength-energy
      model.
AB  - We applied the strength-energy model of self-control to understand the
      relationship between self-control and young athletes' behavioral responses to
      taking illegal performance-enhancing substances, or "doping." Measures of trait
      self-control, attitude and intention toward doping, intention toward, and
      adherence to, doping-avoidant behaviors, and the prevention of unintended doping
      behaviors were administered to 410 young Australian athletes. Participants also
      completed a "lollipop" decision-making protocol that simulated avoidance of
      unintended doping. Hierarchical linear multiple regression analyses revealed that
      self-control was negatively associated with doping attitude and intention, and
      positively associated with the intention and adherence to doping-avoidant
      behaviors, and refusal to take or eat the unfamiliar candy offered in the
      "lollipop" protocol. Consistent with the strength-energy model, athletes with low
      self-control were more likely to have heightened attitude and intention toward
      doping, and reduced intention, behavioral adherence, and awareness of doping
      avoidance. 

PMID- 25996113
TI  - Biochemical analysis of respiratory metabolism in the heterofermentative
      Lactobacillus spicheri and Lactobacillus reuteri.
AB  - AIMS: This study evaluated the aerobic and respiratory metabolism in
      Lactobacillus reuteri and Lactobacillus spicheri, two heterofermentative species
      used in sourdough fermentation. METHODS AND RESULTS: In silico genome analysis,
      production of metabolites and gene expression of pyruvate oxidase, pyruvate
      dehydrogenase and cytochrome oxidase were assessed in anaerobic and aerobic
      cultures of Lact. reuteri and Lact. spicheri. Respiring homofermentative
      Lactobacillus casei N87 and Lact. rhamnosus N132 were used for comparison.
      Aerobiosis and respiration increased the biomass production of heterofermentative
      strains compared to anaerobic cultivation. Respiration led to acetoin production
      by Lact. rhamnosus and Lact. casei, but not in heterofermentative strains, in
      which lactate and acetate were the major end-products. Lactobacillus spicheri
      LP38 showed the highest oxygen uptake. Pyruvate oxidase, respiratory cytochromes,
      NADH oxidase and NADH peroxidase were present in the genome of Lact. spicheri
      LP38. Both Lact. spicheri LP38 and Lact. rhamnosus N132 overexpressed pox in
      aerobic cultures, while cydA was up-regulated only when haeme was supplied; pdh
      was repressed during aerobic growth. CONCLUSIONS: Aerobic and respiratory growth
      provided physiological and metabolic advantages also in heterofermentative
      lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: The exploitation of oxygen
      tolerant phenotypes of Lact. spicheri may be useful for the development of
      improved starter cultures.

PMID- 25996115
TI  - Nanocomposite hydrogels: an emerging biomimetic platform for myocardial therapy
      and tissue engineering.

PMID- 25996116
TI  - Highlights from the latest articles in nanomedicine for reproductive oncology.

PMID- 25996117
TI  - Functional behavior and gene expression of magnetic nanoparticle-loaded primary
      endothelial cells for targeting vascular stents.
AB  - AIM: To assess functional competence and gene expression of magnetic nanoparticle
      (MNP)-loaded primary endothelial cells (ECs) as potential cell-based therapy
      vectors. MATERIALS & METHODS: A quantitative tube formation, nitric oxide and
      adhesion assays were conducted to assess functional potency of the MNP-loaded
      ECs. A quantitative real-time PCR was used to profile genes in both MNP-loaded at
      static conditions and in vitro targeted ECs. RESULTS: Functional behavior of MNP
      loaded and unloaded cells was comparable. MNPs induce expression of genes
      involved in EC growth and survival, while repress genes involved in coagulation.
      CONCLUSION: MNPs do not adversely affect cellular function. Gene expression
      indicates that targeting MNP-loaded ECs to vascular stents may potentially
      stimulate re-endothelialization of an implant and attenuate neointimal
      hyperplasia.

PMID- 25996119
TI  - Nanodiagnostics, nanopharmacology and nanotoxicology of platelet-vessel wall
      interactions.
AB  - In physiological conditions, the interactions between blood platelets and
      endothelial cells play a major role in vascular reactivity and hemostasis. By
      contrast, increased platelet activation contributes to the pathogenesis of
      vascular pathology such as atherosclerosis, thrombosis, diabetes mellitus,
      hypertension and carcinogenesis. Nanomedicine, including nanodiagnostics and
      nanotherapeutics is poised to be used in the management of vascular diseases.
      However, the inherent risk and potential toxicity resultant from the use of
      nanosized (<100 nm) materials need to be carefully considered. This review,
      basing on a systematic search of literature provides state-of-the-art and focuses
      on new discoveries, as well as the potential benefits and threats in the field of
      nanodiagnostics, nanopharmacology and nanotoxicology of platelet-vessel wall
      interactions. 

PMID- 25996118
TI  - Comparison of nanoparticle penetration into solid tumors and sites of
      inflammation: studies using targeted and nontargeted liposomes.
AB  - AIM: The vast majority of nanomedicine research is focused on the use of
      nanoparticles for the diagnosis and treatment of cancer. However, the dense
      extracellular matrix of solid tumors restricts nanoparticle penetration, raising
      the question of whether the best applications of nanomedicines lie in oncology.
      MATERIALS & METHODS: In this study, the uptake of folate-conjugated liposomes was
      compared between folate receptor-expressing tumors and folate receptor+
      inflammatory lesions within the same mouse. RESULTS: We demonstrate here that
      both folate-targeted and nontargeted liposomes accumulate more readily at sites
      of inflammation than in solid tumors. CONCLUSION: These data suggest that
      nanosized imaging and therapeutic agents may be better suited for the treatment
      and diagnosis of inflammatory/autoimmune diseases than cancer.

PMID- 25996120
TI  - Luminescent lanthanide nanomaterials: an emerging tool for theranostic
      applications.
AB  - Lanthanide materials have been gaining popularity for use in various theranostic
      applications, primarily due to their unique optical properties such as narrow
      emission bands, multiple emission wavelengths, emission tunability, long
      fluorescence lifetime and large Stokes shift. Apart from these, some lanthanide
      materials also exhibit magnetic and light-up conversion properties. Such
      nanomaterials have been used for a wide range of applications ranging from
      detection of biomarkers, in vitro and in vivo imaging to therapeutic
      applications. Recently, combined modalities of lanthanide nanomaterials for
      simultaneous detection/imaging and delivery of therapeutic agents (termed
      'theranostics') have been explored. The various advantages and disadvantages of
      using lanthanide nanomaterials as theranostic agents and potential areas for
      future development have been discussed in this review. 

PMID- 25996121
TI  - Nanoparticles functionalized with supramolecular host-guest systems for
      nanomedicine and healthcare.
AB  - Synthetic macrocyclic host compounds can interact with suitable guest molecules
      via noncovalent interactions to form functional supramolecular systems. With the
      synergistic integration of the response of molecules and the unique properties at
      the nanoscale, nanoparticles functionalized with the host-guest supramolecular
      systems have shown great potentials for a broad range of applications in the
      fields of nanoscience and nanotechnology. In this review article, we focus on the
      applications of the nanoparticles functionalized with supramolecular host-guest
      systems in nanomedicine and healthcare, including therapeutic delivery, imaging,
      sensing and removal of harmful substances. A large number of examples are
      included to elucidate the working mechanisms, advantages, limitations and future
      developments of the nanoparticle-supramolecule systems in these applications. 

PMID- 25996122
TI  - Nanoformulations for therapy of pancreatic and liver cancers.
AB  - Pancreatic and liver cancers often have poor prognoses. Clinically, pancreatic
      and liver cancer requires early diagnosis, and surgery is often associated with
      tumor recurrence. Currently, chemotherapies are limited in their ability to
      accurately target the tumors, and are associated with significant toxicity in
      patients. Targeting of chemotherapy can be improved by encapsulation in
      nanocarriers. A variety of preclinical studies indicate relatively superior
      therapeutic outcomes compared with drug alone therapy. Targeted nanoparticle
      imaging agents may also additionally facilitate better diagnosis and improve
      patient outcomes. This review discusses the nanoformulations that are under
      investigation (mainly preclinical studies, but also with some current clinical
      trial examples) against pancreatic and liver cancers, understands the challenges
      and provides future perspectives. 

PMID- 25996123
TI  - Corrigendum.

PMID- 25996124
TI  - Self-induced Orbital Compression Injury: Saturday Night Retinopathy.

PMID- 25996125
TI  - Synthesis of CuInS2 nanocrystals from a molecular complex - characterization of
      the orthorhombic domain structure.
AB  - CuInS2 nanocrystals were synthesized by thermal decomposition of the molecular
      precursor [(Me3P)3Cu(SC2H4S)In(i)Pr2] in the presence of oleylamine in dioctyl
      phthalate. According to X-ray diffraction patterns, the as-synthesized CuInS2
      nanocrystals crystallize in the wurtzite type structure. High-resolution
      transmission electron images and selected area electron diffraction patterns
      reveal a nanodomain structure. The individual domains are approximately 5-10 nm
      in size and characterized by short-range cation ordering, which assuming
      hypothetical long-range order, corresponds to an orthorhombic superstructure
      (space group Pmc21, a = 4.09 +/- 0.01 A, b = 7.16 +/- 0.02 A and c = 6.56 +/-
      0.03 A). The domains are separated by twin and antiphase boundaries. 

PMID- 25996126
TI  - A four-organ-chip for interconnected long-term co-culture of human intestine,
      liver, skin and kidney equivalents.
AB  - Systemic absorption and metabolism of drugs in the small intestine, metabolism by
      the liver as well as excretion by the kidney are key determinants of efficacy and
      safety for therapeutic candidates. However, these systemic responses of applied
      substances lack in most in vitro assays. In this study, a microphysiological
      system maintaining the functionality of four organs over 28 days in co-culture
      has been established at a minute but standardized microsystem scale. Preformed
      human intestine and skin models have been integrated into the four-organ-chip on
      standard cell culture inserts at a size 100,000-fold smaller than their human
      counterpart organs. A 3D-based spheroid, equivalent to ten liver lobules, mimics
      liver function. Finally, a barrier segregating the media flow through the organs
      from fluids excreted by the kidney has been generated by a polymeric membrane
      covered by a monolayer of human proximal tubule epithelial cells. A peristaltic
      on-chip micropump ensures pulsatile media flow interconnecting the four tissue
      culture compartments through microfluidic channels. A second microfluidic circuit
      ensures drainage of the fluid excreted through the kidney epithelial cell layer.
      This four-organ-chip system assures near to physiological fluid-to-tissue ratios.
      In-depth metabolic and gene analysis revealed the establishment of reproducible
      homeostasis among the co-cultures within two to four days, sustainable over at
      least 28 days independent of the individual human cell line or tissue donor
      background used for each organ equivalent. Lastly, 3D imaging two-photon
      microscopy visualised details of spatiotemporal segregation of the two
      microfluidic flows by proximal tubule epithelia. To our knowledge, this study is
      the first approach to establish a system for in vitro microfluidic ADME profiling
      and repeated dose systemic toxicity testing of drug candidates over 28 days.

PMID- 25996127
TI  - Evaluation of silver-titanium implants activated by low intensity direct current
      for orthopedic infection control: An in vitro and in vivo study.
AB  - Silver is an alternative antimicrobial of interest for the prophylaxis of
      prosthetic infections and electrical activation is known to augment its
      oligodynamic efficacy. In this study, we evaluated the in vitro and in vivo
      efficacy of a silver (Ag)-titanium (Ti) implant activated by 30 uA direct current
      compared with three controls - passive Ag-Ti, active Ti-Ti, and passive Ti-Ti. We
      hypothesized that the experimental group would provide better resistance to
      pathogenic colonization on the implant. Modified Kirby-Bauer technique was used
      to evaluate in vitro efficacy of the four groups against five bacteria and one
      fungus. For in vivo evaluation, forty-eight rats were divided into four groups.
      The implant was secured in a wound cavity along the posterior margin of the
      femur. The wound was inoculated with 7.5 * 10(5) CFU of Staphylococcus aureus.
      Rats were euthanized 14 days postsurgery and quantitative cultures were performed
      on the implant segments and the wound cavity tissue. In vitro tests showed that
      the growth of all six pathogens was inhibited around the active Ag anodes of the
      experimental group. In vivo, none of the four groups were able to prevent wound
      infection, but the experimental group resulted in reduced colonization. The mean
      bacterial loads on Ti segments were significantly lower in the implants which
      also had an Ag segment (p = 0.0007), and this effect was more pronounced with
      electrical activation (p = 0.0377). The results demonstrate the antimicrobial
      potential of LIDC-activated Ag-Ti implants. (c) 2015 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 104B: 1023-1031, 2016.

PMID- 25996128
TI  - Using opioid receptors to expand the chemogenetic and optogenetic toolbox.
AB  - In this issue of Neuron, innovative new modifications to opioid receptors are
      used to expand the tools available to modulate neuronal activity. Vardy et al.
      (2015) describe a new "DREADD" chemogenetic tool based on the inhibitory kappa
      opioid receptor (KORD) that can be used in conjunction with already-available
      DREADDs. Siuda et al. (2015) report the development of "opto-MOR," a light
      activatable MU opioid receptor (MOR) chimera that can be used to better
      understand the complexities of MOR signaling. 

PMID- 25996129
TI  - Following directions from the retina to the brain.
AB  - Different types of retinal ganglion cells (RGCs) project to distinct brain
      targets. In this issue of Neuron, Osterhout et al. (2015) and Sun et al. (2015)
      identify how direction-selective RGC axons match with their targets and the
      consequences for visual function when targeting is impaired. 

PMID- 25996130
TI  - Seeing Anew through Interneuron Transplantation.
AB  - Critical periods are developmental time windows during which neuronal connections
      are shaped by experience. In this issue of Neuron, Davis et al. (2015) show that
      transplantation of embryonic inhibitory interneurons can reactivate critical
      period plasticity and reverse amblyopia in the visual cortex of adult mice. 

PMID- 25996131
TI  - Ghosts in the decision machine.
AB  - Humans and monkeys occasionally report the presence of a stimulus that has not
      occurred. A new study by Carnevale et al. (2015) sheds light on the nature and
      timing of the neural mechanisms that give rise to false detections. 

PMID- 25996133
TI  - A cellular perspective on brain energy metabolism and functional imaging.
AB  - The energy demands of the brain are high: they account for at least 20% of the
      body's energy consumption. Evolutionary studies indicate that the emergence of
      higher cognitive functions in humans is associated with an increased glucose
      utilization and expression of energy metabolism genes. Functional brain imaging
      techniques such as fMRI and PET, which are widely used in human neuroscience
      studies, detect signals that monitor energy delivery and use in register with
      neuronal activity. Recent technological advances in metabolic studies with
      cellular resolution have afforded decisive insights into the understanding of the
      cellular and molecular bases of the coupling between neuronal activity and energy
      metabolism and point at a key role of neuron-astrocyte metabolic interactions.
      This article reviews some of the most salient features emerging from recent
      studies and aims at providing an integration of brain energy metabolism across
      resolution scales.

PMID- 25996134
TI  - The stroke-migraine depolarization continuum.
AB  - The term spreading depolarization (SD) refers to waves of abrupt, sustained mass
      depolarization in gray matter of the CNS. SD, which spreads from neuron to neuron
      in affected tissue, is characterized by a rapid near-breakdown of the neuronal
      transmembrane ion gradients. SD can be induced by hypoxic conditions--such as
      from ischemia--and facilitates neuronal death in energy-compromised tissue. SD
      has also been implicated in migraine aura, where SD is assumed to ascend in well
      nourished tissue and is typically benign. In addition to these two ends of the
      "SD continuum," an SD wave can propagate from an energy-depleted tissue into
      surrounding, well-nourished tissue, as is often the case in stroke and brain
      trauma. This review presents the neurobiology of SD--its triggers and propagation
      mechanisms--as well as clinical manifestations of SD, including overlaps and
      differences between migraine aura and stroke, and recent developments in
      neuromonitoring aimed at better diagnosis and more targeted treatments.

PMID- 25996135
TI  - Effective Connectivity between Hippocampus and Ventromedial Prefrontal Cortex
      Controls Preferential Choices from Memory.
AB  - Although many preferential choices in everyday life require remembering relevant
      information, the interplay of neural systems mediating decisions and memory has
      rarely been studied. We addressed this question by combining a task, in which
      choice options had to be retrieved from memory, with cognitive modeling and fMRI.
      We found that memory-guided decisions are captured by established process models
      of choice (sequential sampling models) but constrained by forgetting. People are
      biased toward remembered options and reject them only if they are very
      unattractive. Using a Bayesian modeling approach, we determined the posterior
      probability that options were remembered given the observed choices. This
      probability correlated with hippocampal activation during encoding. During
      decision making, the bias toward remembered options was linked to increased
      connectivity between hippocampus and ventromedial prefrontal cortex. Our results
      provide insights into the dependency of decisions on memory constraints and show
      that memory-related activation can be inferred from decisions.

PMID- 25996136
TI  - Lineage Tracing Using Cux2-Cre and Cux2-CreERT2 Mice.
AB  - Using genetic fate-mapping with Cux2-Cre and Cux2-CreERT2 mice we demonstrated
      that the neocortical ventricular zone (VZ) contains radial glial cells (RGCs)
      with restricted fate potentials (Franco et al., 2012). Using the same mouse
      lines, Guo et al. (2013) concluded that the neocortical VZ does not contain
      lineage-restricted RGCs. We now show that the recombination pattern in Cux2
      Cre/CreERT2 mice depends on genetic background and breeding strategies. We
      provide evidence that Guo et al. likely reached different conclusions because
      they worked with transgenic sublines with drifted transgene expression patterns.
      In Cux2-Cre and Cux2-CreERT2 mice that recapitulate the endogenous Cux2
      expression pattern, the vast majority of fate-mapped neurons express Satb2 but
      not Ctip2, confirming that a restricted subset of all neocortical projection
      neurons belongs to the Cux2 lineage. This Matters Arising paper is in response to
      Guo et al. (2013), published in Neuron. See also the Matters Arising Response
      paper by Eckler et al. (2015), published concurrently with this Matters Arising
      in Neuron.

PMID- 25996137
TI  - Cux2-positive radial glial cells generate diverse subtypes of neocortical
      projection neurons and macroglia.
AB  - We recently published genetic lineage-tracing experiments using the Fezf2 and
      Cux2 loci. These experiments demonstrated that at both the clonal and population
      levels Fezf2(+) RGCs are multipotent and that at the population level Cux2(+)
      RGCs are multipotent. Here, we extend our work on the lineages of Fezf2(+) and
      Cux2(+) RGCs. Clonal analysis of E10.5 neocortical progenitors suggests that
      most, if not all, Cux2(+) and Fezf2(+) RGCs generate diverse projection neuron
      subtypes located throughout layers 2-6. These results support our previous
      conclusion that both Fezf2(+) and Cux2(+) RGCs are multipotent neocortical
      progenitors. This Matters Arising Response paper addresses the Gil-Sanz et al.
      (2015) Matters Arising paper, published concurrently in Neuron. 

PMID- 25996138
TI  - Curbing the Diabetes Pandemic: The Need for Global Policy Solutions.

PMID- 25996132
TI  - The challenge of understanding the brain: where we stand in 2015.
AB  - Starting with the work of Cajal more than 100 years ago, neuroscience has sought
      to understand how the cells of the brain give rise to cognitive functions. How
      far has neuroscience progressed in this endeavor? This Perspective assesses
      progress in elucidating five basic brain processes: visual recognition, long-term
      memory, short-term memory, action selection, and motor control. Each of these
      processes entails several levels of analysis: the behavioral properties, the
      underlying computational algorithm, and the cellular/network mechanisms that
      implement that algorithm. At this juncture, while many questions remain
      unanswered, achievements in several areas of research have made it possible to
      relate specific properties of brain networks to cognitive functions. What has
      been learned reveals, at least in rough outline, how cognitive processes can be
      an emergent property of neurons and their connections. 

PMID- 25996139
TI  - Critical care ultrasonography differentiates ARDS, pulmonary edema, and other
      causes in the early course of acute hypoxemic respiratory failure.
AB  - BACKGROUND: Pathogenic causes of acute hypoxemic respiratory failure (AHRF) can
      be difficult to identify at early clinical presentation. We evaluated the
      diagnostic utility of combined cardiac and thoracic critical care ultrasonography
      (CCUS). METHODS: Adult patients in the ICU were prospectively enrolled from
      January through September 2010 with a Pao2/Fio2 ratio < 300 on arterial blood gas
      (ABG) analysis within 6 h of a new hypoxemic event or the ICU admission. Focused
      cardiac and thoracic CCUS was conducted within 6 h of ABG testing. Causes of AHRF
      were categorized into cardiogenic pulmonary edema (CPE), ARDS, and miscellaneous
      causes after reviewing the hospitalization course in electronic medical records.
      RESULTS: One hundred thirty-four patients were enrolled (median Pao2/Fio2 ratio,
      191; interquartile range, 122-253). Fifty-nine patients (44%) received a
      diagnosis of CPE; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis of
      CCUS findings showed that a low B-line ratio (proportion of chest zones with
      positive B-lines relative to all zones examined) was predictive of miscellaneous
      cause vs CPE or ARDS (receiver operating characteristic area under the curve
      [AUC], 0.82; 95% CI, 0.75-0.88). For further differentiation of CPE from ARDS,
      left-sided pleural effusion (> 20 mm), moderately or severely decreased left
      ventricular function, and a large inferior vena cava minimal diameter (> 23 mm)
      were predictive of CPE (AUC, 0.79; 95% CI, 0.70-0.87). CONCLUSIONS: Combined
      cardiac and thoracic CCUS assists in early bedside differential diagnosis of
      ARDS, CPE, and other causes of AHRF.

PMID- 25996140
TI  - In Silico Profiling of the Potentiality of Curcumin and Conventional Drugs for
      CagA Oncoprotein Inactivation.
AB  - The oncoprotein cytotoxic associated gene A (CagA) of Helicobacter pylori plays a
      pivotal role in the development of gastric cancer, so it has been an important
      target for anti-H. pylori drugs. Conventional drugs are currently being
      implemented against H. pylori. The inhibitory role of plant metabolites like
      curcumin against H. pylori is still a major scientific challenge. Curcumin may
      represent a novel promising drug against H. pylori infection without producing
      side effects. In the present study, a comparative analysis between curcumin and
      conventional drugs (clarithromycin, amoxicillin, pantoprazole, and metronidazole)
      was carried out using databases to investigate the potential of curcumin against
      H. pylori targeting the CagA oncoprotein. Curcumin was filtered using Lipinski's
      rule of five and the druglikeness property for evaluation of pharmacological
      properties. Subsequently, molecular docking was employed to determine the binding
      affinities of curcumin and conventional drugs to the CagA oncoprotein. According
      to the results obtained from FireDock, the binding energy of curcumin was higher
      than those of amoxicillin, pantoprazole, and metronidazole, except for
      clarithromycin, which had the highest binding energy. Accordingly, curcumin may
      become a promising lead compound against CagA+ H. pylori infection. 

PMID- 25996144
TI  - Performance of lateral flow device and galactomannan for the detection of
      Aspergillus species in bronchoalveolar fluid of patients at risk for invasive
      pulmonary aspergillosis.
AB  - Early diagnosis of invasive pulmonary aspergillosis (IPA) remains difficult due
      to the variable performance of the tests used. We compared the performance
      characteristics of Aspergillus lateral flow device (LFD) in bronchoalveolar
      lavage (BAL) vs. BAL-galactomannan (GM), for the diagnosis of IPA. 311 BAL
      specimens were prospectively collected from patients who underwent bronchoscopy
      from January to May 2013. Patients at risk for IPA were divided into
      haematological malignancy (HEM) and non-HEM groups: solid organ transplants (SOT)
      (lung transplant (LT) and non-LT SOT); chronic steroid use (CSU); solid tumour
      (STU) and others. We identified 96 patients at risk for IPA; 89 patients (93%)
      were in the non-HEM groups: SOT 57 (LT, 46, non-LT SOT, 11); CSU 21; STU 6, other
      5. Only three patients met criteria for IA (two probable; one possible). Overall
      sensitivity (SS) was 66% for both and specificity (SP) was 94% vs. 52% for LFD
      and GM respectively. LFD and GM performance was similar in the HEM group (SS 100%
      for both and SP 83% vs. 100% respectively). LFD performance was better than GM
      among non-HEM SOT patients (P = 0.02). Most false-positive GM results occurred in
      the SOT group (50.8%), especially among LT patients (56.5%). LFD performance was
      superior with an overall SP of 95.6% in SOT (P < 0.002) and 97% in LT patients (P
      = 0.0008). LFD is a rapid and simple test that can be performed on BAL to rule
      out IPA. 

PMID- 25996145
TI  - High Prevalence of Methicillin-Resistant Staphylococcus aureus among Patients
      with Septic Arthritis Caused by Staphylococcus aureus.
AB  - BACKGROUND: This study investigated the clinical characteristics of patients with
      septic arthritis caused by Staphylococcus aureus and tried to identify the risk
      factors for methicillin-resistant S. aureus (MRSA) arthritis. METHODS: Between
      January 2008 and December 2011, patients with septic arthritis caused by S.
      aureus were identified from the computerized databases of a regional hospital and
      a medical center in southern Taiwan. The medical records of these patients were
      retrospectively reviewed. RESULTS: A total of 93 patients with S. aureus
      arthritis were identified, and MRSA arthritis was found in 38 (40.9%) cases. The
      mean age of the patients was 58 years, and 86 (92.5%) episodes were classified as
      community-acquired infections. Diabetes mellitus (n = 41, 44.1%) was the most
      common underlying disease, followed by chronic kidney disease and liver
      cirrhosis. Patients with MRSA arthritis were more frequently elderly and found in
      the setting of healthcare-associated infection than patients with methicillin
      susceptible S. aureus (MSSA) infections. No other significant differences in
      clinical manifestations and outcomes were noted between these two groups of
      patients. Overall, the in-hospital mortality rate was 5.4%, and diabetes mellitus
      was the only risk factor for mortality. CONCLUSIONS: MRSA is emerging in the
      setting of community-acquired septic arthritis. MRSA septic arthritis is more
      likely to develop in the elderly and in healthcare-associated infections than
      MSSA septic arthritis.

PMID- 25996146
TI  - Dietary patterns and household food insecurity in rural populations of Kilosa
      district, Tanzania.
AB  - INTRODUCTION: Few studies have investigated the relationship between dietary
      pattern and household food insecurity. The objective of the present analysis was
      to describe the food consumption patterns and to relate these with the prevalence
      of food insecurity in the context of a rural community. METHODOLOGY: Three
      hundred and seven (307) randomly selected households in Kilosa district
      participated in the study. Data were collected during the rainy season (February
      May) and post harvest season (September-October) in the year 2011. Food
      consumption pattern was determined using a 24-h dietary recall method. Food
      insecurity data were based on the 30 day recall experience to food insecurity in
      the household. Factor analysis method using Principal Components extraction
      function was used to derive the dietary patterns and correlation analysis was
      used to establish the existing relationship between household food insecurity and
      dietary patterns factor score. RESULTS: Four food consumption patterns namely (I)
      Meat and milk; (II) Pulses, legumes, nuts and cooking oils; (III) fish (and other
      sea foods), roots and tubers; (IV) Cereals, vegetables and fruits consumption
      patterns were identified during harvest season. Dietary patterns identified
      during the rainy season were as follows: (I) Fruits, cooking oils, fats, roots
      and tubers (II) Eggs, meat, milk and milk products (III) Fish, other sea foods,
      vegetables, roots and tubers and (IV) Pulses, legumes, nuts, cereals and
      vegetables. Household food insecurity was 80% and 69% during rainy and harvest
      seasons, respectively (P = 0.01). Household food insecurity access scale score
      was negatively correlated with the factor scores on household dietary diversity.
      CONCLUSION: Food consumption patterns and food insecurity varied by seasons with
      worst scenarios most prevalent during the rainy season. The risk for inadequate
      dietary diversity was higher among food insecure households compared to food
      secure households. Effort geared at alleviating household food insecurity could
      contribute to consumption of a wide range of food items at the household level.

PMID- 25996147
TI  - Solubilization of tea seed oil in a food-grade water-dilutable microemulsion.
AB  - Food-grade microemulsions containing oleic acid, ethanol, Tween 20, and water
      were formulated as a carrier system for tea seed oil (Camellia oleifera Abel.).
      The effect of ethanol on the phase behavior of the microemulsion system was
      clearly reflected in pseudo-ternary diagrams. The solubilization capacity and
      solubilization efficiency of tea seed oil dispersions were measured along the
      dilution line at a 70/30 surfactant/oil mass ratio with Tween 20 as the
      surfactant and oleic acid and ethanol (1:3, w/w) as the oil phase. The dispersed
      phase of the microemulsion (1.5% weight ratio of tea seed oil to the total amount
      of oil, surfactant, and tea seed oil) could be fully diluted with water without
      phase separation. Differential scanning calorimetry and viscosity measurements
      indicated that both the carrier and solubilized systems underwent a similar
      microstructure transition upon dilution. The dispersion phases gradually inverted
      from the water-in-oil phase (< 35% water) to the bicontinuous phase (40-45%
      water) and finally to the oil-in-water phase (> 45% water) along the dilution
      line. 

PMID- 25996148
TI  - Regulators associated with clinical outcomes revealed by DNA methylation data in
      breast cancer.
AB  - The regulatory architecture of breast cancer is extraordinarily complex and gene
      misregulation can occur at many levels, with transcriptional malfunction being a
      major cause. This dysfunctional process typically involves additional regulatory
      modulators including DNA methylation. Thus, the interplay between transcription
      factor (TF) binding and DNA methylation are two components of a cancer regulatory
      interactome presumed to display correlated signals. As proof of concept, we
      performed a systematic motif-based in silico analysis to infer all potential TFs
      that are involved in breast cancer prognosis through an association with DNA
      methylation changes. Using breast cancer DNA methylation and clinical data
      derived from The Cancer Genome Atlas (TCGA), we carried out a systematic
      inference of TFs whose misregulation underlie different clinical subtypes of
      breast cancer. Our analysis identified TFs known to be associated with clinical
      outcomes of p53 and ER (estrogen receptor) subtypes of breast cancer, while also
      predicting new TFs that may also be involved. Furthermore, our results suggest
      that misregulation in breast cancer can be caused by the binding of alternative
      factors to the binding sites of TFs whose activity has been ablated. Overall,
      this study provides a comprehensive analysis that links DNA methylation to TF
      binding to patient prognosis. 

PMID- 25996150
TI  - Interobserver agreement in detecting spectral-domain optical coherence tomography
      features of diabetic macular edema.
AB  - PURPOSE: To evaluate interobserver agreement for the detection of spectral-domain
      optical coherence tomography (SDOCT) features of diabetic macular edema (DME).
      METHOD: Cross-sectional study in which 2 retinal specialists evaluated SDOCT
      scans from eyes receiving treatment for DME. Scans from 50 eyes with DME of 39
      patients were graded for features of DME including intra-retinal fluid (IRF),
      diffuse retinal oedema (DRE), hyper-reflective foci (HRF), subretinal fluid
      (SRF), macular fluid and vitreomacular traction (VMT). Features were graded as
      present or absent at zones involving the fovea, 1mm from the fovea and the whole
      scan of 49 line scans. Analysis was performed using cross-tabulations for
      percentage concordance and kappa values (kappa). RESULTS: In the 2950 line scans
      analysed, there was an increase in percentage concordance for DRE and HRF when
      moving from a foveal line scan, 1mm zone and then to a whole scan analysis (88%
      vs 94% vs 96%) and (88% vs 94% vs 94%) respectively with kappa ranging from
      substantial to almost perfect. Percentage concordance for SRF was 96% at all 3
      regions analysed, whilst IRF was 96% at fovea and 98% at higher number of line
      scans analysed. Concordance for MF was 100% at fovea and 98% at 1mm zone and
      whole scan with almost perfect and substantial kappa respectively. kappa
      agreement was substantial for VMT at all regions analysed. CONCLUSION: We report
      a high level of interobserver agreement in the detection of SDOCT features of
      DME. This finding is important as detection of macular fluid is used to guide
      retreatment with anti-angiogenic agents.

PMID- 25996149
TI  - Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor.
AB  - Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently
      reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma
      to promote cancer cell survival. Here we identified HRP-3 as a new endothelial
      ligand and characterized its in vitro and in vivo functional roles and molecular
      signaling. We combined open reading frame phage display with multi-round in vivo
      binding selection to enrich retinal endothelial ligands, which were
      systematically identified by next generation DNA sequencing. One of the
      identified endothelial ligands was HRP-3. HRP-3 expression in the retina and
      brain was characterized by Western blot and immunohistochemistry. Cell
      proliferation assay showed that HRP-3 stimulated the growth of human umbilical
      vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in
      culture. Wound healing assay indicated that HRP-3 promoted endothelial cell
      migration. HRP-3 was further confirmed for its in vitro angiogenic activity by
      spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal
      regulated kinase 1/2 (ERK1/2) pathway in endothelial cells. The angiogenic
      activity of HRP-3 was independently verified by mouse cornea pocket assay.
      Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote
      new blood vessel formation. These results demonstrated that HRP-3 is a novel
      angiogenic factor. 

PMID- 25996151
TI  - Association between Prenatal and Postnatal Psychological Distress and Toddler
      Cognitive Development: A Systematic Review.
AB  - PURPOSE: Maternal psychological distress is one of the most common perinatal
      complications, affecting up to 25% of pregnant and postpartum women. Research
      exploring the association between prenatal and postnatal distress and toddler
      cognitive development has not been systematically compiled. The objective of this
      systematic review was to determine the association between prenatal and postnatal
      psychological distress and toddler cognitive development. METHODS: Articles were
      included if: a) they were observational studies published in English; b) the
      exposure was prenatal or postnatal psychological distress; c) cognitive
      development was assessed from 13 to 36 months; d) the sample was recruited in
      developed countries; and e) exposed and unexposed women were included. A
      university-based librarian conducted a search of electronic databases (Embase,
      CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray
      literature, reference lists, and relevant journals. Two reviewers independently
      evaluated titles/abstracts for inclusion, and quality using the Scottish
      Intercollegiate Guideline Network appraisal tool for observational studies. One
      reviewer extracted data using a standardized form. RESULTS: Thirteen of 2448
      studies were included. There is evidence of an association between prenatal and
      postnatal distress and cognitive development. While variable effect sizes were
      reported for postnatal associations, most studies reported medium effect sizes
      for the association between prenatal psychological distress and cognitive
      development. Too few studies were available to determine the influence of the
      timing of prenatal exposure on cognitive outcomes. CONCLUSION: Findings support
      the need for early identification and treatment of perinatal mental health
      problems as a potential strategy for optimizing toddler cognitive development.

PMID- 25996152
TI  - Online training on skin cancer diagnosis in rheumatologists: results from a
      nationwide randomized web-based survey.
AB  - Patients with inflammatory rheumatisms, such as rheumatoid arthritis, are more
      prone to develop skin cancers than the general population, with an additional
      increased incidence when receiving TNF blockers. There is therefore a need that
      physicians treating patients affected with inflammatory rheumatisms with TNF
      blockers recognize malignant skin lesions, requiring an urgent referral to the
      dermatologist and a potential withdrawal or modification of the immunomodulatory
      treatment. We aimed to demonstrate that an online training dedicated to skin
      tumors increase the abilities of rheumatologists to discriminate skin cancers
      from benign skin tumors. A nationwide randomized web-based survey involving 141
      French rheumatologists was conducted. The baseline evaluation included short
      cases with skin lesion pictures and multiple choice questions assessing basic
      knowledge on skin cancers. For each case, rheumatologists had to indicate the
      nature of skin lesion (benign; premalignant/malignant), their level of confidence
      in this diagnosis (10-points Likert scale), and the precise dermatological
      diagnosis among 5 propositions. Different scores were established. After
      randomization, only one group had access to the online formation consisting in 4
      e-learning modules on skin tumors, of 15 minutes each (online training group).
      After reevaluation, the trained and the non-trained group (control group) were
      compared. The primary end-point was the number of adequate diagnoses of the
      nature of the skin lesions. The mean number of adequate diagnosis for the benign
      versus premalignant/malignant nature of the lesions was higher in the online
      training group (13.4 vs. 11.2 points; p value <0.0001). While the other knowledge
      scores were also significantly higher, no statistical difference was observed on
      the level of self-confidence between the 2 groups. In conclusion, the online
      formation was effective to improve the rheumatologists' ability to diagnose skin
      cancer. 

PMID- 25996153
TI  - Stochastic time models of syllable structure.
AB  - Drawing on phonology research within the generative linguistics tradition,
      stochastic methods, and notions from complex systems, we develop a modelling
      paradigm linking phonological structure, expressed in terms of syllables, to
      speech movement data acquired with 3D electromagnetic articulography and X-ray
      microbeam methods. The essential variable in the models is syllable structure.
      When mapped to discrete coordination topologies, syllabic organization imposes
      systematic patterns of variability on the temporal dynamics of speech
      articulation. We simulated these dynamics under different syllabic parses and
      evaluated simulations against experimental data from Arabic and English, two
      languages claimed to parse similar strings of segments into different syllabic
      structures. Model simulations replicated several key experimental results,
      including the fallibility of past phonetic heuristics for syllable structure, and
      exposed the range of conditions under which such heuristics remain valid. More
      importantly, the modelling approach consistently diagnosed syllable structure
      proving resilient to multiple sources of variability in experimental data
      including measurement variability, speaker variability, and contextual
      variability. Prospects for extensions of our modelling paradigm to acoustic data
      are also discussed. 

PMID- 25996155
TI  - Ejaculated mouse sperm enter cumulus-oocyte complexes more efficiently in vitro
      than epididymal sperm.
AB  - The mouse is an established and popular animal model for studying reproductive
      biology. Epididymal mouse sperm, which lack exposure to secretions of male
      accessory glands and do not precisely represent ejaculated sperm for the study of
      sperm functions, have been almost exclusively used in studies. We compared
      ejaculated and epididymal sperm in an in vitro fertilization setting to examine
      whether ejaculated sperm enter cumulus-oocyte complexes more efficiently. In
      order to prepare sperm for fertilization, they were incubated under capacitating
      conditions. At the outset of incubation, ejaculated sperm stuck to the glass
      surfaces of slides and the incidences of sticking decreased with time; whereas,
      very few epididymal sperm stuck to glass at any time point, indicating
      differences in surface charge. At the end of the capacitating incubation, when
      sperm were added to cumulus-oocyte complexes, the form of flagellar movement
      differed dramatically; specifically, ejaculated sperm predominantly exhibited
      increased bending on one side of the flagellum (a process termed pro-hook
      hyperactivation), while epididymal sperm equally exhibited increased bending on
      one or the other side of the flagellum (pro-hook or anti-hook hyperactivation).
      This indicates that accessory sex gland secretions might have modified Ca2+
      signaling activities in sperm, because the two forms of hyperactivation are
      reported to be triggered by different Ca2+ signaling patterns. Lastly, over time,
      more ejaculated than epididymal sperm entered the cumulus oocyte complexes. We
      concluded that modification of sperm by male accessory gland secretions affects
      the behavior of ejaculated sperm, possibly providing them with an advantage over
      epididymal sperm for reaching the eggs in vivo. 

PMID- 25996154
TI  - Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human
      Pulmonary Tuberculosis.
AB  - Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high
      mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of
      matrix destruction resulting in cavitation is not well defined. Neutrophils are
      emerging as key mediators of TB immunopathology and their influx are associated
      with poor outcomes. We investigated neutrophil-dependent mechanisms involved in
      TB-associated matrix destruction using a cellular model, a cohort of 108
      patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB
      dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and
      caused matrix destruction both in vitro and in respiratory samples of TB
      patients. Collagen destruction induced by TB infection was abolished by
      doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs)
      contain MMP-8 and are increased in samples from TB patients. Neutrophils lined
      the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations
      reflected TB radiological and clinical disease severity. AMPK, a central
      regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from
      AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing
      neutrophils are present in human TB lung biopsies with phospho-AMPK detected in
      nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in
      the immunopathology of TB and is a potential target for host-directed therapy in
      this infectious disease. 

PMID- 25996156
TI  - Pectin Enhances Bio-Control Efficacy by Inducing Colonization and Secretion of
      Secondary Metabolites by Bacillus amyloliquefaciens SQY 162 in the Rhizosphere of
      Tobacco.
AB  - Bacillus amyloliquefaciens is a plant-beneficial Gram-positive bacterium involved
      in suppressing soil-borne pathogens through the secretion of secondary
      metabolites and high rhizosphere competence. Biofilm formation is regarded as a
      prerequisite for high rhizosphere competence. In this work, we show that plant
      extracts affect the chemotaxis and biofilm formation of B. amyloliquefaciens SQY
      162 (SQY 162). All carbohydrates tested induced the chemotaxis and biofilm
      formation of the SQY 162 strain; however, the bacterial growth rate was not
      influenced by the addition of carbohydrates. A strong chemotactic response and
      biofilm formation of SQY 162 were both induced by pectin through stimulation of
      surfactin synthesis and transcriptional expression of biofilm formation related
      matrix genes. These results suggested that pectin might serve as an environmental
      factor in the stimulation of the biofilm formation of SQY 162. Furthermore, in
      pot experiments the surfactin production and the population of SQY 162 in the
      rhizosphere significantly increased with the addition of sucrose or pectin,
      whereas the abundance of the bacterial pathogen Ralstonia decreased. With
      increased production of secondary metabolites in the rhizosphere of tobacco by
      SQY 162 and improved colonization density of SQY 162 in the pectin treatment, the
      disease incidences of bacterial wilt were efficiently suppressed. The present
      study revealed that certain plant extracts might serve as energy sources or
      environmental cues for SQY 162 to enhance the population density on tobacco root
      and bio-control efficacy of tobacco bacterial wilt. 

PMID- 25996157
TI  - Parasitism in Children Aged Three Years and Under: Relationship between Infection
      and Growth in Rural Coastal Kenya.
AB  - BACKGROUND: Parasitic infections, which are among the most common infections
      worldwide, disproportionately affect children; however, little is known about the
      impact of parasitic disease on growth in very early childhood. Our objective was
      to document the prevalence of parasitic infections and examine their association
      with growth during the first three years of life among children in coastal Kenya.
      METHODOLOGY/PRINCIPAL FINDINGS: Children enrolled in a maternal-child cohort were
      tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm,
      Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia),
      filaria, and Schistosoma infection every six months from birth until age three
      years. Anthropometrics were measured at each visit. We used generalized
      estimating equation (GEE) models to examine the relationship between parasitic
      infections experienced in the first three years of life and growth outcomes
      (weight, length and head circumference). Of 545 children, STHs were the most
      common infection with 106 infections (19%) by age three years. Malaria followed
      in period prevalence with 68 infections (12%) by three years of age. Filaria and
      Schistosoma infection occurred in 26 (4.8%) and 16 (2.9%) children, respectively.
      Seven percent were infected with multiple parasites by three years of age. Each
      infection type (when all STHs were combined) was documented by six months of age.
      Decreases in growth of weight, length and head circumference during the first 36
      months of life were associated with hookworm, Ascaris, E. histolytica, malaria
      and Schistosoma infection. In a subset analysis of 180 children who followed up
      at every visit through 24 months, infection with any parasite was associated with
      decelerations in weight, length and head circumference growth velocity. Multiple
      infections were associated with greater impairment of linear growth.
      CONCLUSIONS/SIGNIFICANCE: Our results demonstrate an under-recognized burden of
      parasitism in the first three years of childhood in rural Kenya. Parasitic
      infection and polyparasitism were common, and were associated with a range of
      significant growth impairment in terms of weight, length and/or head
      circumference.

PMID- 25996159
TI  - Controlled Synthesis of ZrS2 Monolayer and Few Layers on Hexagonal Boron Nitride.
AB  - Group IVB transition metal (Zr and Hf) dichalcogenide (TMD) monolayers can have
      higher carrier mobility and higher tunneling current density than group VIB (Mo
      and W) TMD monolayers. Here we report the synthesis of hexagonal ZrS2 monolayer
      and few layers on hexagonal boron nitride (BN) using ZrCl4 and S as precursors.
      The domain size of ZrS2 hexagons is around 1-3 MUm. The number of layers of ZrS2
      was controlled by tuning the evaporation temperature of ZrCl4. The stacking angle
      between ZrS2 and BN characterized by transmission electron microscopy shows a
      preferred stacking angle of near 0 degrees . Field-effect transistors (FETs)
      fabricated on ZrS2 flakes showed n-type transport behavior with an estimated
      mobility of 0.1-1.1 cm(2) V(-1) s(-1). 

PMID- 25996158
TI  - Evidence for the Presence of Glucosensor Mechanisms Not Dependent on Glucokinase
      in Hypothalamus and Hindbrain of Rainbow Trout (Oncorhynchus mykiss).
AB  - We hypothesize that glucosensor mechanisms other than that mediated by
      glucokinase (GK) operate in hypothalamus and hindbrain of the carnivorous fish
      species rainbow trout and stress affected them. Therefore, we evaluated in these
      areas changes in parameters which could be related to putative glucosensor
      mechanisms based on liver X receptor (LXR), mitochondrial activity, sweet taste
      receptor, and sodium/glucose co-transporter 1 (SGLT-1) 6 h after intraperitoneal
      injection of 5 mL x Kg(-1) of saline solution alone (normoglycaemic treatment) or
      containing insulin (hypoglycaemic treatment, 4 mg bovine insulin x Kg(-1) body
      mass), or D-glucose (hyperglycaemic treatment, 500 mg x Kg(-1) body mass). Half
      of tanks were kept at a 10 Kg fish mass x m(-3) and denoted as fish under normal
      stocking density (NSD) whereas the remaining tanks were kept at a stressful high
      stocking density (70 kg fish mass x m(-3)) denoted as HSD. The results obtained
      in non-stressed rainbow trout provide evidence, for the first time in fish, that
      manipulation of glucose levels induce changes in parameters which could be
      related to putative glucosensor systems based on LXR, mitochondrial activity and
      sweet taste receptor in hypothalamus, and a system based on SGLT-1 in hindbrain.
      Stress altered the response of parameters related to these systems to changes in
      glycaemia.

PMID- 25996160
TI  - Controllable Sequential Deposition of Planar CH3NH3PbI3 Perovskite Films via
      Adjustable Volume Expansion.
AB  - We demonstrate a facile morphology-controllable sequential deposition of planar
      CH3NH3PbI3 (MAPbI3) film by using a novel volume-expansion-adjustable PbI2.xMAI
      (x: 0.1-0.3) precursor film to replace pure PbI2. The use of additive MAI during
      the first step of deposition leads to the reduced crystallinity of PbI2 and the
      pre-expansion of PbI2 into PbI2.xMAI with adjustable morphology, which result in
      about 10-fold faster formation of planar MAPbI3 film (without PbI2 residue) and
      thus minimize the negative impact of the solvent isopropanol on perovskites
      during the MAI intercalation/conversion step. The best efficiency obtained for a
      planar perovskite solar cell based on PbI2.0.15MAI is 17.22% (under one sun
      illumination), which is consistent with the stabilized maximum power output at an
      efficiency of 16.9%. 

PMID- 25996161
TI  - E-cigarettes and pregnancy. Is a closer look appropriate?

PMID- 25996162
TI  - Biocompatible Fe-Si Nanoparticles with Adjustable Self-Regulation of Temperature
      for Medical Applications.
AB  - Because of the noninvasive, locally selective potential of thermal energy,
      considerable effort has been focused on the use of an external, alternating
      magnetic field for conversion of magnetic work to heat with iron oxide
      nanoparticles. However, proper regulation of thermal energy remains a challenge
      because of the lack of feedback from the local temperature change to the external
      power supply. Here, we show development of smart magnetic nanoparticles composed
      of Fe and Si with intrinsically tunable heat generation capability. They were
      engineered to possess an adjustable magnetic transition temperature through
      tuning the exchange between Fe atoms by incorporation of silicon atoms. They show
      relatively high magnetic moment. Moreover, their biocompatibility was established
      in several cell lines. The nanoparticles were also combined with a
      thermosensitive polymer, which had the capability to release of molecules with a
      magnetic stimulus, thereby providing a platform for locally controlled, drug
      release. 

PMID- 25996163
TI  - Nitrogen Stereodynamics and Complexation Phenomena as Key Factors in the
      Deprotonative Dynamic Resolution of Alkylideneaziridines: A Spectroscopic and
      Computational Study.
AB  - The present work is aimed at shedding light on the origin of the
      stereoselectivity observed in the reactions of chiral heterosubstituted
      organolithiums, generated by lithiation of alkylideneaziridines. Factors such as
      the nitrogen inversion barrier, the stereochemistry at the nitrogen atom, the
      substitution pattern of the alkylideneaziridines, and the reaction conditions are
      taken into consideration. The interplay between nitrogen stereodynamics and
      complexation phenomena seems to be crucial in determining the stereochemical
      outcome of the lithiation/trapping sequence. The findings were rationalized by a
      synergistic use of NMR experiments, run on the lithiated intermediates, alongside
      computational data. It has been demonstrated that, in such systems, the
      stereochemistry-determining step is the deprotonation reaction, and a model based
      on a deprotonative dynamic resolution has been proposed. Such findings could find
      application in dynamic systems other than aziridines. 

PMID- 25996166
TI  - The molecular pathogenesis of B-cell non-Hodgkin lymphoma.
AB  - The B-cell non-Hodgkin lymphomas (B-NHL) are a diverse group of haematological
      malignancies which arise from the mature B-lymphocyte compartment. Recently, our
      understanding of the molecular pathogenesis of these disorders has greatly
      increased due to technological advances such as high-throughput DNA sequencing
      techniques. A paradigm of B-NHL pathogenesis has emerged where the normal genetic
      processes that are central to generating B-cell receptor diversity (somatic
      hypermutation and class switch/VDJ recombination) also drive the genesis of large
      scale, chromosomal-level genetic lesions and smaller-scale gene-level mutations
      to produce the malignant phenotypes observed. Whilst a significant degree of
      genetic heterogeneity exists within each B-NHL subtype, the genetic lesions
      present within each subtype show a degree of convergence on common intracellular
      signalling, epigenetic and cell cycle pathways. This convergence gives an insight
      into the key oncogenic drivers of specific B-NHL subtypes and potential targets
      for therapeutic intervention. This review covers the current understanding of the
      causative genetic processes of B-NHL, the associated driving molecular lesions
      and the implications of these findings for the treatment of this group of
      disorders. 

PMID- 25996165
TI  - Structural Insights into Bound Water in Crystalline Amino Acids: Experimental and
      Theoretical (17)O NMR.
AB  - We demonstrate here that the (17)O NMR properties of bound water in a series of
      amino acids and dipeptides can be determined with a combination of nonspinning
      and magic-angle spinning experiments using a range of magnetic field strengths
      from 9.4 to 21.1 T. Furthermore, we propose a (17)O chemical shift fingerprint
      region for bound water molecules in biological solids that is well outside the
      previously determined ranges for carbonyl, carboxylic, and hydroxyl oxygens,
      thereby offering the ability to resolve multiple (17)O environments using rapid
      one-dimensional NMR techniques. Finally, we compare our experimental data against
      quantum chemical calculations using GIPAW and hybrid-DFT, finding intriguing
      discrepancies between the electric field gradients calculated from structures
      determined by X-ray and neutron diffraction. 

PMID- 25996167
TI  - Peroxynitrite Decomposition Catalyst Reduces Delayed Thrombolysis-induced
      Hemorrhagic Transformation in Ischemia-reperfused Rat Brains.
AB  - AIM: Hemorrhagic transformation (HT) is a major complication of delayed tissue
      plasminogen activator (t-PA) treatment in ischemic stroke. We aimed to explore
      whether peroxynitrite decomposition catalyst (PDC) could prevent such
      complication. METHODS: Male Sprague-Dawley (SD) rats were subjected to middle
      cerebral artery occlusion (MCAO) with t-PA (10 mg/kg) or t-PA plus FeTMPyP (3
      mg/kg, a representative PDC) at MCAO for 2 or 5 h and reperfusion for 22 or 19 h,
      respectively. HT was assessed with hemoglobin assay. Neurological deficit was
      evaluated with Modified Neurological Severity Score (mNSS). Peroxynitrite
      formation was examined by detecting 3-nitrotyrosine (3-NT) formation. The
      expression and activity of MMP-9/MMP-2 were assessed by Western blotting and
      gelatin zymography. RESULTS: t-PA treatment at 2 h of MCAO did not induce HT but
      attenuated neurological deficit, whereas treatment at 5 h significantly induced
      HT and worsened the neurological outcome. Such complications were prevented by
      FeTMPyP cotreatment. Early t-PA treatment inhibited 3-NT and MMP-9/MMP-2
      expression, whereas delayed treatment induced 3-NT and MMP-9/MMP-2 expression and
      activity. FeTMPyP cotreatment downregulated 3-NT and inhibited MMP-9/MMP-2 in
      both time points. CONCLUSION: Peroxynitrite decomposition catalyst could prevent
      hemorrhagic transformation and improve neurological outcome ischemic rat brains
      with delayed t-PA treatment via inhibiting peroxynitrite-mediated MMP activation.

PMID- 25996168
TI  - Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1
      signal pathways in the auditory cortex of a mimetic aging rat model: changes to
      Trx2 in the auditory cortex.
AB  - Age-associated degeneration in the central auditory system, which is defined as
      central presbycusis, can impair sound localization and speech perception.
      Research has shown that oxidative stress plays a central role in the pathological
      process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin
      family, plays a key role in regulating the homeostasis of cellular reactive
      oxygen species and anti-apoptosis. The purpose of this study was to explore the
      association between Trx2 and the phenotype of central presbycusis using a mimetic
      aging animal model induced by long-term exposure to d-galactose (d-Gal). We also
      explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal
      regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well
      as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic
      aging rats. Our results demonstrate that, compared with control groups, the
      levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas
      TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly
      increased in the auditory cortex of the mimetic aging groups. Our results
      indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may
      participate in the pathogenesis of central presbycusis. 

PMID- 25996169
TI  - Transfer of Acanthamoeba spp. to fresh produce from water and environmental
      surfaces.
AB  - Human noroviruses (HuNoV) are the primary cause of food-borne disease outbreaks
      in the United States. The most frequent commodities implicated in HuNoV outbreaks
      are leafy greens where contamination may occur during production and harvesting
      practices. With respect to the transmission of HuNoV to fresh produce, one
      hypothesis is that free-living amoebae that are ubiquitous in the environment
      (soil, sediments and water) can serve as vehicles of contamination through
      interaction with viruses. Here, we investigated the transfer of Acanthamoeba spp.
      both alone and associated with murine norovirus (MNV-1)-a surrogate for HuNoV
      from water and food contact surfaces to fresh produce to understand the transfer
      of amoebae and the effect of virus association with amoeba on transferability, if
      any. In water containing a low concentration of amoebae (3 log10  cell ml(-1) ),
      3.85 log10 amoebae transferred to 5 g of leafy greens, and for 5 cherry tomatoes,
      3.4 to 3.5 log10 amoebae were transferred. Similarly, for high concentrations of
      amoeba (5 log10  cell ml(-1) ) in water, 6.14 and 5.81 log10 amoebae were
      transferred to 5 g leafy greens and five cherry tomatoes respectively. However,
      the transfer of amoebae from food contact surfaces to fresh produce was very
      limited. In addition, amoebae association with MNV-1 did not impact
      transferability. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study
      provide a better understanding of physical parameters (e.g. surface area and
      texture of fresh produce, transfer medium-water vs surface) potentially
      associated with transfer of free-living amoeba to fresh produce as well as the
      role that contaminated water (irrigation or wash water) may play in the
      transmission of enteric viruses associated with amoeba.

PMID- 25996170
TI  - Incidence of joint replacement among active component service members, U.S. Armed
      Forces, 2004-2014.
AB  - In the U.S., joint replacements have become more common and the average age of
      individuals who undergo joint replacements has decreased. Joint replacements
      among active component service members increased 10.5% during 2004-2009, then
      61.9% during 2009-2014. Knees and hips were the most frequently replaced joints
      among service members. During the surveillance period (and particularly after
      2009), incidence rates increased in each age group of service members 30 years or
      older. Relative to their respective counterparts, rates of joint replacement
      overall--and of the hip and knee specifically--were higher among service members
      who were black, non-Hispanic; officers; and healthcare workers. One year after
      joint replacement, 18.2% had retired; 5.2% had been medically disqualified from
      service; 6.3% had otherwise left service; and 70.3% were still in service. By 2
      years post-joint replacement, 30.2% had retired; 13.0% had been medically
      disqualified; 10.0% had otherwise left service; and 46.8% were still in service.
      Service members aged 30-44 years were the most likely to remain in service post
      joint replacement. Given the increases in the frequency of joint replacement
      among younger service members, the number of service members who remain in
      service post-joint replacement may continue to increase.

PMID- 25996171
TI  - Case series: Chikungunya and dengue at a forward operating location.

PMID- 25996172
TI  - Tdap vaccination coverage during pregnancy, active component service women, 2006
      2014.
AB  - Tetanus, diphtheria, and acellular pertussis (Tdap) vaccines have been licensed
      for use in the U.S. since 2006 and have been recommended during pregnancy since
      2011. Low vaccination coverage during pregnancy among the general U.S. population
      has been reported. Therefore, this surveillance study was conducted to assess the
      percentage of service women with a live birth delivery during 2006-2014 who
      received a Tdap vaccination during their pregnancy. Only 1%-3% of service women
      during 2006-2011 received a Tdap vaccine during their pregnancy. However,
      coverage increased to 8% in 2012 and 54% in 2014. Although this moderate Tdap
      coverage among military service women is an improvement over past years, more
      education and attention by military physicians and pregnant service women to the
      benefits of Tdap vaccination are needed to bring coverage closer to 100%. 

PMID- 25996173
TI  - Surveillance snapshot: Influenza vaccination coverage during pregnancy, active
      component service women, October 2009-April 2014.

PMID- 25996176
TI  - Probiotics: The scientific evidence in the context of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) generally comprises Crohn's disease (CD) and
      ulcerative colitis (UC), and their main characteristic is the intestinal mucosa
      inflammation. Although its origin is not yet fully known, there is growing
      evidence related to genetics, intestinal microbiota composition, and the immune
      system factors such as precursors for the initiation and progression of
      intestinal conditions. The use of certain probiotic microorganisms has been
      touted as a possible and promising therapeutic approach in reducing the risk of
      inflammatory bowel disease, specifically ulcerative colitis. Several mechanisms
      have been proposed to explain the benefits of probiotics, indicating that some
      bacterial strains are able to positively modulate the intestinal microbiota and
      the immune system, and to produce metabolites with anti-inflammatory properties.
      The aim of this paper is to bring together the various results and information,
      based on scientific evidence, that are related to probiotics and inflammatory
      bowel disease, emphasizing the possible mechanisms involved in this action.

PMID- 25996177
TI  - Enhancing plant productivity while suppressing biofilm growth in a windowfarm
      system using beneficial bacteria and ultraviolet irradiation.
AB  - Common problems in a windowfarm system (a vertical and indoor hydroponic system)
      are phytopathogen infections in plants and excessive buildup of biofilms. The
      objectives of this study were (i) to promote plant health by making plants more
      resistant to infection by using beneficial biosurfactant-producing Pseudomonas
      chlororaphis around the roots and (ii) to minimize biofilm buildup by ultraviolet
      (UV) irradiation of the water reservoir, thereby extending the lifespan of the
      whole system with minimal maintenance. Pseudomonas chlororaphis-treated lettuce
      grew significantly better than nontreated lettuce, as indicated by enhancement of
      color, mass, length, and number of leaves per head (p < 0.05). The death rate of
      the lettuce was reduced by ~ 50% when the lettuce was treated with P.
      chlororaphis. UV irradiation reduced the bacteria (4 log reduction) and algae (4
      log reduction) in the water reservoirs and water tubing systems. Introduction of
      P. chlororaphis into the system promoted plant growth and reduced damage caused
      by the plant pathogen Pythium ultimum. UV irradiation of the water reservoir
      reduced algal and biofilm growth and extended the lifespan of the system.

PMID- 25996178
TI  - The object of your affection: how commitment, leadership and justice influence
      workplace behaviours in health care.
AB  - AIM: This paper describes the development of a coherent framework that develops
      nursing knowledge and guides research in workplace behaviours, work performance,
      and the factors that influence behaviours and performance. BACKGROUND: Work
      performance is dependent upon behaviours that are related to one's commitment
      towards their workplace and leadership interactions. The influence of these
      concepts on work outcomes has been established in disparate studies, but their
      precedence in terms of influencing workers' behaviours, is not well understood.
      METHODS: A scientific realism approach is applied, where theory and current
      research in the field of organisational behaviour and work motivation are drawn
      upon to identify validated constructs and explain their relationships.
      DISCUSSION: An augmented framework is produced, incorporating concepts of
      relevance to work motivation and work attitudes. Propositions, predicated on
      research evidence, are offered. Conclusions A novel comprehensive framework is
      developed, extending the range of behaviours important to workers and the
      organisation. IMPLICATIONS FOR NURSING MANAGEMENT: Focusing on targets for which
      nurses are affectively committed can prove useful to managers. The developed
      framework can be informative to managers by increasing awareness of the
      relationships between concepts, such that they are mindful of these constructs
      while interacting with staff.

PMID- 25996179
TI  - Prevalence, risk factors and underdiagnosis of asthma and wheezing in adults 40
      years and older: A population-based study.
AB  - OBJECTIVE: There are differences in the prevalence and risk factors of asthma
      around the world. The epidemiological situation of adults 40 years and older is
      not well established. Our aim was to determine the prevalence, underdiagnosis and
      risk factors of asthma and wheezing in adults in Colombia. METHODS: A cross
      sectional, population-based study including 5539 subjects from 40 to 93 years
      selected by a probabilistic sampling technique in five cities was conducted.
      MEASUREMENTS: respiratory symptoms and risk factors questionnaire and spirometry.
      DEFINITIONS: (a) Wheezing: Affirmative answer to the question "have you ever had
      two or more attacks of "wheezes" causing you to feel short of breath?" (b)
      Asthma: Wheezing definition and FEV1/FVC post-bronchodilator >= 70%. (c)
      Underdiagnosis: Asthma definition without a physician-diagnosis. Logistic
      regression was used for exploring risk factors. RESULTS: Prevalence of asthma was
      9.0% (95% CI: 8.3-9.8) and wheezing 11.9% (95% CI: 11.0-12.8). Asthma
      underdiagnosis was 69.9% and increased to 79.0% in subjects 64 years or older.
      The risk factors related to asthma and/or wheezing were: living in Bogota or
      Medellin, female gender, first degree relative with asthma, respiratory disease
      before 16 years of age, obesity, no education, indoor wood smoke exposure and
      occupational exposure to dust particles, gases or fumes. CONCLUSION: We described
      the epidemiologic situation of asthma in adults 40 years and older in Colombia.
      In addition to some recognized risk factors, our data supports the association of
      indoor wood smoke and occupational exposures with asthma and wheezing.
      Underdiagnosis of asthma in adults was high, particularly in older subjects.

PMID- 25996180
TI  - Effects of Ovariectomy and Corticosteroid-Induced Osteoporosis on the
      Osteoinductivity of rhBMP-2 in a Segmental Long-Bone Defect Model.
AB  - This study used the segmental long-bone defect model to assess the effects of
      osteoporosis on the formation of new bones and the osteoinductivity of
      recombinant human bone morphogenetic protein-2 (rhBMP-2). Seventy-two female
      Sprague-Dawley rats were divided into two groups: an osteoporosis group with
      ovariectomies and dexamathasone intramuscular injections and a sham group. When
      they reached 22 weeks in age, each group was further divided into two groups and
      a 5-mm defect was made in both fibular mid-shafts of each rat. One fibula in each
      rat was picked randomly and was injected with 0.05 mL of hydrogel carrier; the
      opposite fibula was injected with the same carrier mixed with rhBMP-2 (10 MUg).
      After rearing for a further 5 and 9 weeks, the ratios of the lengths of the newly
      formed bones in the fibular defects were determined using micro-CT and
      undecalcified histology. The sham rhBMP-2-injected group-in all of the 5- and 9
      week-kept groups-showed a significantly higher bridging bone formation ratio than
      the other three groups. The osteoporosis rhBMP-2-injected group showed a
      significantly higher ratio than both the non-rhBMP-2-injected sham hydrogel and
      the osteoporosis hydrogel groups. The comparison of the micro-CT parameters of
      the newly formed bones showed that the sham rhBMP-2 group at both 5 and 9 weeks
      compared with the osteoporosis rhBMP-2 group had significantly higher percentage
      bone volumes, trabecular thicknesses, and trabecular numbers, in addition to
      significantly lower specific surfaces, trabecular pattern factors, and structural
      model indices. The histology results showed that the sham-rhBMP-2 group began
      forming bridging bones in the defect areas at 5 weeks, and at 9 weeks, trabeculae
      and marrow spaces were observed. However, the osteoporosis rhBMP-2 group
      exhibited a relatively minor level of new bone and trabecula formation.
      Consequently, the rhBMP-2 group showed significantly increased bone formation in
      the osteoporosis rat fibular defect model compared with the hydrogel group,
      whereas the new bone quantities, qualities, and remodeling in the osteoporosis
      rhBMP-2 group were less effective than those in the sham-rhBMP-2 group, signaling
      that ovariectomy and corticosteroid-induced osteoporosis significantly undermines
      rhBMP-2 osteoinductivity. 

PMID- 25996181
TI  - Development and Implementation of an Interactive Text Messaging Campaign to
      Support Behavior Change in a Childhood Obesity Randomized Controlled Trial.
AB  - Text messaging is a promising means of intervening on an array of health issues
      among varied populations, but little has been published about the development of
      such interventions. The authors describe the development and implementation of an
      interactive text messaging campaign for parents to support behavior change among
      children in a childhood obesity randomized controlled trial. The authors invited
      160 parents to participate in a text messaging intervention that provided
      behavior change support in conjunction with health coaching phone calls and
      mailed materials on behavioral goals. Throughout the 1-year intervention, the
      authors sent 1-2 text messages per week. The first asked how the child did with a
      target behavior the day before; parents who replied received an immediate
      feedback message tailored to their response. The second included a tip about how
      to work toward a behavioral goal. Baseline surveys indicate that text messaging
      is a common means of communication for parents, and many are willing to use text
      messaging to support behavior change for their child. Results at 1 year indicate
      a high level of engagement with the text messaging intervention, with nearly two
      thirds responding to 75% or more of the questions they were sent by text. 

PMID- 25996185
TI  - Tea Consumption and Endometrial Cancer Risk: Meta-Analysis of Prospective Cohort
      Studies.
AB  - Several lines of evidence suggest that tea consumption may reduce the risk of
      endometrial cancer due to antioxidant properties of tea, but the results of
      prospective data to date are inconsistent. We thus conducted a meta-analysis of
      prospective cohort studies to examine the relationship between tea consumption
      and endometrial cancer risk, using a random-effects model. We identified 5
      eligible cohort studies, which included 231,870 female participants and 1831
      cases for endometrial cancer. The pooled relative risk (RR) for the highest
      (median 2 cups/day) vs. no/lowest category of tea consumption on endometrial
      cancer risk was 0.95 [95% confidence interval (CI): 0.80-1.12] with no
      significant heterogeneity (P for heterogeneity = 0.68, I(2) = 0.0%). By country
      of origin, the pooled RR of 3 studies conducted in the United States was 1.00
      (95% CI: 0.83-1.21), in which black tea was consumed by most people. Because of
      limited data on Asian population, the association of green tea on endometrial
      cancer was not calculated separately. There was no indication of publication bias
      (Begg's P = 0.46; Egger's P = 0.43). Our findings from prospective data do not
      support a role of tea consumption in endometrial carcinogenesis. More prospective
      cohort studies with green tea consumption should be conducted.

PMID- 25996186
TI  - Bacterial d-amino acid oxidases: Recent findings and future perspectives.
AB  - D-Amino acid oxidase (DAO) is a flavin enzyme that catalyzes the oxidative
      deamination of d-amino acids. This enzyme has been studied extensively both
      biochemically and structurally as a model for the oxidase-dehydrogenase class of
      flavoproteins. This enzyme also has various applications, such as the
      determination of d-amino acids and production of building blocks for a number of
      pharmaceuticals. DAO has been found mainly in eukaryotic organisms and has been
      suggested to play a significant role in various cellular processes, one of which
      includes neurotransmission in the human brain. In contrast, this enzyme has not
      been identified in prokaryotic organisms. Some studies have recently identified
      and characterized DAO enzyme in some actinobacteria. In addition, a genome
      database search reveals a wide distribution of DAO homologous genes in this
      bacterial group. The bacterial DAOs characterized so far have certain distinct
      properties in comparison to eukaryotic DAOs. These enzymes also exhibit some
      important applicable properties, suggesting that bacteria could be used as a
      source for obtaining novel and useful DAOs. The physiological function of
      bacterial DAO have been proposed to include the degradation of non-canonical d
      amino acids released from cell wall, but is still largely unknown and need to be
      studied in depth. 

PMID- 25996187
TI  - Head-to-head comparison of 10 natriuretic peptide assays.
AB  - BACKGROUND: The aim of the study was to compare NT-proBNP and BNP levels in fresh
      samples from heart failure (HF) patients measured using 10 immunoassays and to
      assess their agreement. METHODS: NT-proBNP (CobasH232((r)), Elecsys((r)),
      Vidas((r)), Vista((r)), XPand((r)), Vitros((r))) and BNP (Triage((r)),
      Access((r)), CentaurXP((r)), Architect((r))) levels were measured in 39 heparin
      and 19 EDTA samples, respectively. RESULTS: The Pearson correlation coefficient
      ranged between 0.929 (Triage((r)-)Centaur((r))) and 0.994 (Access((r))
      Architect((r))) for BNP assays and between 0.972 (Vidas((r))-Cobas H232((r))) and
      0.999 (Vitros((r))-Vidas((r))) for NT-proBNP assays. Passing Bablok regression
      analyses showed a significant difference in the slopes [0.80 (Centaur((r))
      Triage((r))) to 1.84 (Architect((r))-Centaur((r)))] and intercepts [-55 ng/L
      (Architect((r))-Centaur((r))) to 48 ng/L (Access((r))-Triage(r))] for BNP assays,
      and a lower heterogeneity between NT-proBNP assays [0.83 (Vidas((r))
      Elecsys((r))) to 1.20 (Vitros((r))-Vidas((r))) and -97 ng/L (XPand((r))
      CobasH232((r))) to 51 ng/L (CobasH232((r))-Elecsys((r))) for slopes and
      intercepts, respectively]. The concordance correlation coefficient revealed a
      poor (rhoc<0.90) to moderate (rhoc=0.90-0.95) agreement in 4/6 pairs of BNP
      assays and an almost perfect (rhoc>0.99) agreement in 5/15 pairs of NT-proBNP
      assays. The acceptable difference limit reflecting the number of individual
      discrepant results between two assays, ranged between 15.1% (Access((r))
      CentaurXP((r))) and 34.5% (Architect((r))-Triage((r))) for BNP assays, and
      between 10.9% (Vidas((r))-Vitros((r))) and 55% (CobasH232((r))-Xpand((r))) for NT
      proBNP assays. CONCLUSIONS: This study stresses the lack of transferability of
      the results obtained using different techniques to measure BNP and NT-proBNP
      levels in fresh samples. Individual reference ranges and HF diagnostic cut-offs
      should be assessed for each commercial NP immunoassay. We recommend to
      systematically monitoring HF patients using the same assay (BNP or NT-proBNP)
      over the time.

PMID- 25996182
TI  - Oncolytic viruses: From bench to bedside with a focus on safety.
AB  - Oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents.
      Several viruses have undergone evaluation in clinical trials in the last decades,
      and the first agent is about to be approved to be used as a novel cancer therapy
      modality. In the current review, an overview is presented on recent (pre)clinical
      developments in the field of oncolytic viruses that have previously been or
      currently are being evaluated in clinical trials. Special attention is given to
      possible safety issues like toxicity, environmental shedding, mutation and
      reversion to wildtype virus. 

PMID- 25996193
TI  - Iridoid constituents from the male flower of Eucommia ulmoides and their
      promotion proliferation on ESF-1.
AB  - Four new iridoids (1, 2, 12, and 13), together with nine known iridoids (3-11),
      were isolated from the male flowers of Eucommia ulmoides Oliver and were
      characterized as 3beta-methoxyartselawnin C (1), 6beta-hydroxyl-1beta,3beta
      dimethoxyartsclaenin III (2), 3,4-dihydro-3beta-ethoxyasperuloside (12) and 3,4
      dihydro-3beta-ethoxydesacetylasperuloside (13) by extensive analyses of their 1D
      and 2D NMR spectroscopy and mass spectra. All of the isolated compounds were
      assayed for the promoting proliferation of skin fibroblasts cell (ESF-1) and
      compounds 4 and 7 (5 MUM) significantly stimulated the proliferation of ESF-1
      cells.

PMID- 25996194
TI  - Infectious diseases.

PMID- 25996192
TI  - Comparison of methods for the analysis of therapeutic immunoglobulin G Fc
      glycosylation profiles-Part 2: Mass spectrometric methods.
AB  - To monitor the Fc glycosylation of therapeutic immunoglobulin G in bioprocess
      development, product characterization and release analytics, reliable techniques
      for glycosylation analysis are needed. Several analytical methods are suitable
      for this application. We recently presented results comparing detection methods
      for glycan analysis that are separation-based, but did not include mass
      spectrometry (MS). In the study reported here, we comprehensively compared MS
      based methods for Fc glycosylation profiling of an IgG biopharmaceutical. A
      therapeutic antibody reference material was analyzed 6-fold on 2 different days,
      and the methods investigated were compared with respect to precision, accuracy,
      throughput and analysis time. Emphasis was put on the detection and quantitation
      of sialic acid-containing glycans. Eleven MS methods were compared to hydrophilic
      interaction liquid chromatography of 2-aminobenzamide labeled glycans with
      fluorescence detection, which served as a reference method and was also used in
      the first part of the study. The methods compared include electrospray MS of the
      heavy chain and Fc part after limited digestion, liquid chromatography MS of a
      tryptic digest, porous graphitized carbon chromatography MS of released glycans,
      electrospray MS of glycopeptides, as well as matrix assisted laser desorption
      ionization MS of glycans and glycopeptides. Most methods showed excellent
      precision and accuracy. Some differences were observed with regard to the
      detection and quantitation of low abundant glycan species like the sialylated
      glycans and the amount of artefacts due to in-source decay. 

PMID- 25996196
TI  - Nonpolio enterovirus infections in neonates.
AB  - There are currently 12 species and over 100 serotypes that have been identified
      in the enterovirus genus, including the coxsackieviruses, echoviruses, and
      polioviruses. Since their discovery 65 years ago, much has been discovered and
      continues to be researched regarding the pathogenicity and scope of disease of
      nonpolio enteroviruses. Like many infections, enteroviruses have been found to
      affect neonates much differently, and often more severely, than older children
      and adults. Neonatal infections often cause mild illnesses with nonspecific
      symptoms, but they may also have severe presentations involving the
      cardiovascular, gastrointestinal, hematologic, or central nervous systems. This
      article provides an overview of what is known about nonpolio enteroviruses in
      neonates including epidemiology, transmission, clinical presentation, diagnosis,
      and treatment.

PMID- 25996195
TI  - Going against the grain: an atypical presentation of celiac disease.
AB  - With the current prevalence of celiac disease, it is important to know the common
      signs and symptoms of this disease process and to also be aware of atypical
      presentations. This article describes a toddler who initially presented with
      recurrent diarrhea and weight loss with a significant secondary hypokalemia. His
      initial examination included screening for celiac disease, but the serology was
      negative. After persistent and worsening symptoms, further tests were pursued and
      a diagnosis of celiac disease was confirmed based on an upper endoscopy and
      histology.

PMID- 25996197
TI  - A review of the guidelines for the evaluation and treatment of congenital
      syphilis.
AB  - Congenital syphilis (CS) is a disease that continues to persist in the United
      States despite its preventable nature. Mother-to-child transmission of CS can be
      avoided with appropriate maternal diagnosis and treatment during the pregnancy.
      Diagnosing CS and determining the therapeutic course can be challenging. This
      review covers the recent guidelines for the diagnosis and treatment of CS and the
      various factors that affect management decisions. These factors include the
      mother's antenatal management, the infant's clinical presentation and results,
      laboratory and serologic testing, and more.

PMID- 25996198
TI  - Current controversies in diagnosis, management, and prevention of congenital
      cytomegalovirus: updates for the pediatric practitioner.
AB  - Congenital cytomegalovirus (CMV) infection has been called "the elephant in our
      living room" because it is a major public health problem that for decades has
      been unrecognized and unaddressed. Congenital CMV infection is a common cause of
      sensorineural hearing loss, vision loss, neurodevelopment disabilities, liver
      disease, and growth failure. Diagnostic tests are now widely available to
      identify newborns with congenital CMV infection, congenitally infected newborns
      now can be easily assessed for evidence of organ involvement, and there are now
      antiviral treatments and other interventions available to improve the outcome in
      children with congenital CMV disease. A licensed vaccine to prevent CMV infection
      is not yet available; however, a "CMV knowledge vaccine," composed of "an ounce
      of CMV awareness and three simple precautions" and that is endorsed by the
      Centers for Disease Control and Prevention is available for pregnant women who
      wish to reduce their contact with potentially CMV-infected secretions and
      therefore reduce their risk of acquiring CMV during pregnancy. Medical experts in
      the field of congenital CMV have been called upon for a consensus statement for
      diagnosis and treatment, and nonprofit organizations of families affected by
      congenital CMV from around the world have formed a collaborative coalition to
      facilitate the spread of CMV knowledge and awareness.

PMID- 25996199
TI  - Neonatal tuberculosis.
AB  - Tuberculosis remains a prevalent disease worldwide, with approximately 9 million
      cases diagnosed annually. The emergence of multidrug-resistant tuberculosis has
      proven to be a challenging international public health issue. In the United
      States, however, the incidence of tuberculosis has been decreasing since 1992.
      There were just over 9,500 reported cases in 2013, and almost 500 of those were
      in children younger than age 15 years. Foreign-born persons are a high-risk group
      and account for 65% of new cases annually. Other high-risk groups include ethnic
      minorities, HIV-infected patients, and people living in low-socioeconomic urban
      areas.

PMID- 25996200
TI  - Molecular diagnostics and newborns at risk for genital herpes simplex virus.
AB  - Herpes simplex virus (HSV) infection in the newborn carries a high mortality rate
      and can result in lifelong neurologic impairment. The severity of HSV infection
      in the newborn has always dictated conservative management when prodromal
      symptoms or active genital lesions (or those suggestive of genital herpes) are
      present during labor and delivery. The risk of intrapartum infection, however, is
      related to the presence or absence of maternal immunity (neutralizing antibody)
      to HSV. The most significant risk of transmission is in first-episode primary
      infections with active lesions at delivery. Recent recommendations from the
      American Academy of Pediatrics Committees on Infectious Diseases and the Fetus
      and Newborn use rapid serologic and virologic screening in the management of
      asymptomatic infants born to mothers with active genital herpes. The revised
      guidelines highlight infants at greatest risk for HSV disease but do not apply to
      asymptomatic infants born to mothers with a history of HSV but no genital lesions
      at delivery. The current guidelines also stipulate that maternal serologic
      screening and molecular assays for HSV in newborn blood and cerebrospinal fluid
      must be available and reported in a timely fashion.

PMID- 25996201
TI  - 'I don't need an eye for an eye': Women's responses to intimate partner violence
      in Sierra Leone and Liberia.
AB  - This paper explores the possibilities for agency in intimate partner violence
      (IPV) situations from the perspective of women in Sierra Leone and Liberia using
      focus group discussions (N groups = 14, N participants = 110) and individual
      interviews (N = 20). Findings identify multiple interrelated factors influencing
      the decision-making of women experiencing IPV. At the individual level, emotional
      factors and women's knowledge of their rights and options influence their
      decision-making. At the relational level, the role of neighbours, family and
      friends is crucial, both for emotional support and practical assistance. At the
      community level, more formal structures play a role, such as chiefs and women's
      groups, though their effectiveness varies. At the structural level are barriers
      to effective responses, including a poorly functioning criminal justice system
      and a social system in which children often stay with fathers following
      separation or divorce. Strong cultural beliefs operate to keep women in abusive
      relationships. We identify implications for prevention and response services and
      make practice recommendations. Since the desire of most women experiencing IPV
      was to live in peace with their husbands, interventions should respect women's
      priorities by focusing more on prevention and interventions to end the violence,
      rather than solely assisting women to leave violent relationships. 

PMID- 25996202
TI  - Superhydrophobic SAM Modified Electrodes for Enhanced Current Limiting Properties
      in Intrinsic Conducting Polymer Surge Protection Devices.
AB  - Surface interface engineering using superhydrophobic gold electrodes made with 1
      dodecanethiol self-assembled monolayer (SAM) has been used to enhance the current
      limiting properties of novel surge protection devices based on the intrinsic
      conducting polymer, polyaniline doped with methanesulfonic acid. The resulting
      devices show significantly enhanced current limiting characteristics, including
      current saturation, foldback, and negative differential effects. We show how SAM
      modification changes the morphology of the polymer film directly adjacent to the
      electrodes, leading to the formation of an interfacial compact thin film that
      lowers the contact resistance at the Au-polymer interface. We attribute the
      enhanced current limiting properties of the devices to a combination of lower
      contact resistance and increased Joule heating within this interface region which
      during a current surge produces a current blocking resistive barrier due to a
      thermally induced dedoping effect caused by the rapid diffusion of moisture away
      from this region. The effect is exacerbated at higher applied voltages as the
      higher temperature leads to stronger depletion of charge carriers in this region,
      resulting in a negative differential resistance effect. 

PMID- 25996203
TI  - Obturation Techniques Allow Microbial Leakage Unless Protected.
AB  - PURPOSE: To evaluate the quality of the apical 5-mm seal produced by different
      filling techniques using a bacterial leakage model. MATERIALS AND METHODS: Sixty
      five extracted single-rooted human teeth were decoronated, prepared, and
      instrumented. Roots were randomly divided into three experimental groups (15
      roots each) and control groups (10 roots each). The apical 5 mm was filled with
      cold lateral condensation (CLC) technique, continuous wave of condensation (CWC),
      or injectable thermoplasticized gutta-percha (Obtura II) using AH26 Plus as a
      sealer. Positive controls were filled with gutta-percha without sealer, whereas
      negative controls were filled with a CLC technique and covered completely with
      two layers of nail varnish, including the orifice. A dual-chamber leakage model
      using Enterococcus faecalis as a microbial marker was used for leakage
      evaluation. Bacterial penetration was monitored over a 60-day period, and leakage
      was recorded when turbidity was observed in the lower chamber. RESULTS: All
      positive controls exhibited turbidity in the lower chamber within 24 hours. All
      negative controls demonstrated no bacterial leakage for the entire 60-day
      observation period. The estimated mean day for leakage was 32 for CLC, 35 for
      CWC, and 30 days for Obtura II. Wilcoxon test showed no statistically significant
      difference (p = 0.98) in the survival time between the experimental groups.
      CONCLUSION: The three filling techniques produced similar resistance to bacterial
      leakage when used to fill the apical 5-mm segment of the canal while leaving the
      rest of the canal unfilled.

PMID- 25996204
TI  - Diabetes mellitus and the risk of bladder  cancer: an Italian case-control study.
AB  - BACKGROUND: Diabetes mellitus has been associated with an increased risk of
      bladder cancer, although the evidence is still open to discussion. METHODS: We
      examined this association using data from a multicentre Italian case-control
      study, conducted between 2003 and 2014 on 690 bladder cancer cases and 665
      frequency-matched hospital controls. Odds ratios (ORs) for diabetes were
      estimated by unconditional multiple logistic regression models, after allowance
      for major known risk factors for bladder cancer. RESULTS: One hundred and twelve
      (16.2%) cases and 57 (8.6%) controls reported a diagnosis of diabetes mellitus,
      corresponding to a multivariate OR of 2.09 (95% confidence interval (CI): 1.46
      3.01). Bladder cancer risk increased with duration of diabetes (OR 1.92 for 1- <5
      years, 1.63 for 5- <10 years, 2.39 for 10- <15 years, and 2.58 for >=15 years).
      The increased risk of bladder cancer was consistent in strata of age and
      education, whereas it was somewhat lower (although not significantly) in women
      (OR 1.18), in never (OR 1.31) and current (OR 1.42) smokers, and in subjects with
      a body mass index <25 kg m(-2) (OR 1.48). CONCLUSION: The present study provides
      further support of a role of diabetes in bladder cancer aetiology, although some
      residual confounding by tobacco, body mass index, or other unmeasured covariates
      may partly explain the association observed.

PMID- 25996205
TI  - Colposcopy attendance and deprivation: A retrospective analysis of 27,193 women
      in the NHS Cervical Screening Programme.
AB  - BACKGROUND: Attendance for cervical screening is socially graded, but little is
      known about patterns of attendance for colposcopy following an abnormal screening
      result. METHODS: Logistic regression was used to regress colposcopy attendance
      status for 27 193 women against age and area-level deprivation, adjusting for
      ethnicity. RESULTS: Colposcopy attendance was high at 8 weeks (89%) and 4 months
      post-referral (94%) but women living in the most deprived areas were
      significantly less likely to attend. CONCLUSIONS: The high overall attendance
      rates at colposcopy are encouraging but lower attendance among women in the most
      income-deprived areas indicates that even when these women attend primary
      cervical screening, they remain at higher risk of missing out on the benefits of
      the programme.

PMID- 25996207
TI  - Chemistry and biological activity of ramalina lichenized fungi.
AB  - Lichens are a form of symbiont between a fungus and an alga or cyanobacterium,
      which contains a wide variety of organic compounds with certain secondary
      metabolite classes typical of these organisms. The Ramalina genus has
      approximately 246 species distributed around the World, of which in this review
      approximately 118 species with published chemical or biological activity studies
      of extracts or isolated compounds were cited. From the 153 mentioned compounds,
      only 27 passed were tested for biological activity, being usnic acid the most
      studied compound and the one showing the best results in almost all in vitro
      tests performed, although other compounds also presented excellent results as
      antimicrobial, antitumor and anti-inflammatory agents, among others. Extracts of
      several species also presented significant results in performed biological tests,
      demonstrating the potential that these organisms have, in particular, the gender
      Ramalina, to produce bioactive molecules that can be used as a model for the
      production of pharmaceuticals. 

PMID- 25996206
TI  - Case-control study of Epstein-Barr virus and  Helicobacter pylori serology in
      Latin  American patients with gastric disease.
AB  - BACKGROUND: Chronic tissue damage induced by Helicobacter pylori (HP)-driven
      inflammation is considered the main risk of gastric carcinoma (GC). Epstein-Barr
      virus (EBV) infection has also been associated with GC. In this study, we aim to
      address the role of EBV in inflammatory GC precursor lesions and its added risk
      to HP infection. METHODS: Antibodies against EBV, HP and the bacterial virulence
      factor CagA were measured in sera from 525 Mexican and Paraguayan patients with
      gastric disease. Gastric samples were characterised according to the updated
      Sydney classification and associations were estimated between antibody responses
      and severity of both tissue damage and inflammation. RESULTS: We found
      significant associations (odd ratios and trends) between EBV and HP copositivity
      and premalignant lesions and intestinal-type GC. The EBV and HP coinfection was
      also significantly associated with increased infiltration of immune cells. No
      association was found between EBV and the less inflammation-driven diffuse-type
      GC. CONCLUSIONS: Our study suggests that EBV co-participates with HP to induce
      severe inflammation, increasing the risk of progression to intestinal-type GC.

PMID- 25996208
TI  - Inhibitory Effects of Verrucarin A on Tunicamycin-Induced ER Stress in FaO Rat
      Liver Cells.
AB  - Endoplasmic reticulum (ER) stress is linked with development and maintenance of
      cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A,
      isolated from the broth of Fusarium sp. F060190, showed potential inhibitory
      activity on tunicamycin-induced ER stress in FaO rat liver cells. In addition,
      the compound decreased tunicamycin-induced GRP78 promoter activity in a dose
      dependent manner without inducing significant inhibition of luciferase activity
      and cell growth for 6 and 12 h. Moreover, the compound decreased the expression
      of GRP78, CHOP, XBP-1, and suppressed XBP-1, and reduced phosphorylation of
      IRE1alpha in FaO rat liver cells. This evidence suggests for the first time that
      verrucarin A inhibited tunicamycin-induced ER stress in FaO rat liver cells. 

PMID- 25996209
TI  - S4MPLE--Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site
      Docking Benchmarking.
AB  - This paper describes the development of the unified conformational sampling and
      docking tool called Sampler for Multiple Protein-Ligand Entities (S4MPLE). The
      main novelty in S4MPLE is the unified dealing with intra- and intermolecular
      degrees of freedom (DoF). While classically programs are either designed for
      folding or docking, S4MPLE transcends this artificial specialization. It supports
      folding, docking of a flexible ligand into a flexible site and simultaneous
      docking of several ligands. The trick behind it is the formal assimilation of
      inter-molecular to intra-molecular DoF associated to putative inter-molecular
      contact axes. This is implemented within the genetic operators powering a
      Lamarckian Genetic Algorithm (GA). Further novelty includes differentiable
      interaction fingerprints to control population diversity, and fitting a simple
      continuum solvent model and favorable contact bonus terms to the AMBER/GAFF force
      field. Novel applications-docking of fragment-like compounds, simultaneous
      docking of multiple ligands, including free crystallographic waters-were
      published elsewhere. This paper discusses: (a) methodology, (b) set-up of the
      force field energy functions and (c) their validation in classical redocking
      tests. More than 80% success in redocking was achieved (RMSD of top-ranked pose <
      2.0 A). 

PMID- 25996210
TI  - Protein-carbohydrate interactions as part of plant defense and animal immunity.
AB  - The immune system consists of a complex network of cells and molecules that
      interact with each other to initiate the host defense system. Many of these
      interactions involve specific carbohydrate structures and proteins that
      specifically recognize and bind them, in particular lectins. It is well
      established that lectin-carbohydrate interactions play a major role in the immune
      system, in that they mediate and regulate several interactions that are part of
      the immune response. Despite obvious differences between the immune system in
      animals and plants, there are also striking similarities. In both cases, lectins
      can play a role as pattern recognition receptors, recognizing the pathogens and
      initiating the stress response. Although plants do not possess an adaptive immune
      system, they are able to imprint a stress memory, a mechanism in which lectins
      can be involved. This review will focus on the role of lectins in the immune
      system of animals and plants. 

PMID- 25996211
TI  - Effects of Dietary Brazilian Palm Oil (Mauritia flexuosa L.) on Cholesterol
      Profile and Vitamin A and E Status of Rats.
AB  - In vitro studies have been carried out to establish the nutritional differences
      between crude and refined vegetable oils; however, the impact of the consumption
      of these foods on metabolism, in particular the effect of buriti oil, needs to be
      further evaluated. The aim of this study was to evaluate the biochemical and
      murine parameters and the vitamin A and E status in young rats fed with diets
      supplemented with crude or refined buriti oil. The animals (n = 30) were
      randomized into three groups receiving diet added of soybean oil (control), crude
      buriti oil (CBO) and refined buriti oil (RBO) for 28 days. Rats fed with diet
      added of refined buriti oil (RBO) showed reduced total cholesterol (up to
      60.27%), LDL (64.75%), triglycerides (55.47%) and enzyme aspartate transaminase
      (21.57%) compared to those fed with diet added of crude oil. Serum and hepatic
      retinol and tocopherol were higher by two to three times in CBO and RBO groups
      compared to the control group, but no differences were observed for murine
      parameters. The results indicate that buriti oil is an important source of the
      antioxidant vitamins A and E, and refined buriti oil is suggested as alternative
      to improve the lipid profile of healthy rats. 

PMID- 25996212
TI  - Four New Triterpenoids from Callicarpa kwangtungensis.
AB  - Four new triterpenoids which were identifed as 2alpha,3beta,6beta,19alpha
      tetrahydroxy- oleanolic acid 28-O-beta-D-glucopyranoside (1), 2-O-beta-D
      glucopyranosyloxy-3alpha,19alpha-di-hydroxyoleanolic acid (2), 2-O-beta-D
      glucopyranosyloxy-3alpha,19alpha-dihydroxyursolic acid (3),
      2alpha,3alpha,6beta,19alpha-tetrahydroxyursolic acid 28-O-beta-D-glucopyranoside
      (4), were isolated from the aerial parts of Callicarpa kwangtungensis together
      with three known triterpenoids identified as 2alpha,3beta,21beta
      trihydroxyursolic acid 28-O-beta-D-glucopyranoside (5), 2alpha,3alpha,19alpha,23
      tetrahydroxyoleanolic acid 28-O-beta-D-glucopyranoside (6),
      2alpha,3alpha,19alpha,23-tetrahydroxyursolic acid 28-O-beta-D-glucopyranoside
      (7). Their structures were elucidated by the combination of mass spectrometry
      (MS), one and two-dimensional NMR experiments. 

PMID- 25996213
TI  - LC-MS/MS Determination and Pharmacokinetic Study of Pedunculoside in Rat Plasma
      after Oral Administration of Pedunculoside and Ilex rotunda Extract.
AB  - Ilex rotunda is widely used to treat many disorders as a traditional Chinese
      medicine (TCM) containing 4%-5% pedunculoside (PDC). A rapid, selective, and
      sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was
      developed and validated to determine PDC in rat plasma by using 3beta,19alpha
      dihydroxyurs-12-en-28-oic acid 28-beta-D-glucopyranosyl ester (DEOG) as an
      internal standard. The analytes were extracted by protein precipitation and
      eluted on a C18 chromatography column using a mobile phase of methanol-H2O
      (70:30, v/v) delivered at a flow rate of 0.6 mL/min. Detection was performed
      using positive ion electrospray ionization in multiple reaction monitoring modes.
      The assay was linear over the concentration range of 0.60 ng/mL to 200 ng/mL,
      with a quantification limit of 0.60 ng/mL. Intra-day and inter-day precisions
      (%RSD) ranged from 2.12 to 9.51 for PDC, whereas the accuracy was within 
      7.83%~9.40%. The validated method was successfully applied to the pharmacokinetic
      study of PDC in rat plasma after oral administration of pure PDC and Ilex rotunda
      extract (IRE). Pharmacokinetic parameters of PDC in IRE, such as Cmax, AUC0-t,
      AUC0-infinity, t1/2z, and CLz/F, statistically differed from those of the pure
      monomer (p < 0.01). However, Tmax and MRT showed no significant differences
      between the two groups. Results suggested that other coexisting components in IRE
      may decrease the absorption of PDC. Compound-compound interactions between PDC
      and other herbal extract components can alter the pharmacokinetic behavior of
      PDC. The study will be helpful in providing references for understanding the
      action mechanism and clinical application of Ilex rotunda. 

PMID- 25996214
TI  - Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of
      gastrointestinal integrity, protection and ulcer healing.
AB  - Nitric oxide (NO) and hydrogen sulfide (H2S) are known as biological messengers;
      they play an important role in human organism and contribute to many
      physiological and pathophysiological processes. NO is produced from l-arginine by
      constitutive NO synthase (NOS) and inducible NOS enzymatic pathways. This gaseous
      mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the
      vessel homeostasis. NO is known as a vasodilatory molecule involved in control of
      the gastric blood flow (GBF) and the maintenance of gastric mucosal barrier
      integrity in either healthy gastric mucosa or that damaged by strong irritants.
      Biosynthesis of H2S in mammals depends upon two enzymes cystathionine-beta
      synthase and cystathionine gamma-lyase. This gaseous mediator, similarly to NO
      and carbon monoxide, is involved in neuromodulation, vascular contractility and
      anti-inflammatory activities. For decades, H2S has been known to inhibit
      cytochrome c oxidase and reduce cell energy production. Nowadays it is generally
      considered to act through vascular smooth muscle ATP-dependent K+ channels,
      interacting with intracellular transcription factors and promote sulfhydration of
      protein cysteine moieties within the cell, but the mechanism of potential
      gastroprotective and ulcer healing properties of H2S has not been fully
      explained. The aim of this review is to compare current results of the studies
      concerning the role of H2S and NO in gastric mucosa protection and outline areas
      that may pose new opportunities for further development of novel therapeutic
      targets. 

PMID- 25996215
TI  - 1,3-diphenylethenylcarbazolyl-based monomer for cross-linked hole transporting
      layers.
AB  - A new cross-linkable monomer containing 1,3-diphenylethenylcarbazolyl-based hole
      transporting moieties and four reactive epoxy groups, was prepared by a multistep
      synthesis route from 1,3-bis(2,2-diphenylethenyl)-9H-carbazol-2-ol and its
      application for the in situ formation of cross-linked hole transporting layers
      was investigated. A high concentration of flexible aliphatic epoxy chains ensures
      good solubility and makes this compound an attractive cross-linking agent. The
      synthesized compounds were characterized by various techniques, including
      differential scanning calorimetry, xerographic time of flight, and electron
      photoemission in air methods. 

PMID- 25996216
TI  - Nanofibers of cellulose and its derivatives fabricated using direct
      electrospinning.
AB  - A short review with 49 references describes the electrospinninng (ES) process for
      polysaccharides, cellulose and chitosan, and their derivatives, including
      cellulose acetate and hydroxypropyl cellulose. A majority of applied studies
      adopted a two step-process, in which the cellulose acetate was used for the first
      ES process, followed by acetyl group removal to regenerate cellulose thin fibers.
      The electrospun nonwoven fabrics (ESNW) of regenerated cellulose can be modified
      by introduction of aldehyde groups by oxidative cleavage of vicinal diols using
      periodates, and these aldehyde groups serve as acceptors of foreign substances,
      with various chemical/biological functions, to be immobilized on the fiber
      surfaces in the ESNW matrices. Direct electrospinning of cellulose from
      trifluroacetic acid solution was also developed and the applied studies were
      summarized to conclude the current trends of interests in the ES and related
      technologies. 

PMID- 25996217
TI  - Characterization of Anthocyanins in Perilla frutescens var. acuta Extract by
      Advanced UPLC-ESI-IT-TOF-MSn Method and Their Anticancer Bioactivity.
AB  - The anthocyanin extract from a domestic Perilla cultivar (Perilla frutescens var.
      acuta) were isolated and characterized with high mass accuracy and multi
      dimensional fragmentation by means of ultra-performance liquid chromatography
      (UPLC) and electrospray ionization-ion trap-time of flight mass spectrometry
      analysis (ESI-IT-TOF-MSn). The new developed and applied LC-MS method focused on
      in-depth screening of anthocyanin compounds with similar structures which also
      provided a new approach of anthocyanin characterization without the use of
      external standards. Selective detection of interested anthocyanins was achieved
      utilizing extracted ion chromatogram (EIC) analysis, while MSn spectra were
      recorded to allow identification of the anthocyanin based on characteristic
      fragmentation patterns. Seven anthocyanins including one feruloyl (Cyanidin 3-O
      feruloylglucoside-5-O-glucoside), two caffeoyl (Cyanidin 3-O-caffeoylglucoside-5
      O-glucoside, Cyanidin 3-O-caffeoylglucoside-5-O-malonylglucoside) and four
      coumaroyl substituted anthocyanins (Cis-shisonin, Malonyl-cis-shisonin, Shisonin,
      and Malonyl-shisonin) were identified. Annexin-V FITC/PI flow cytometric assay
      was performed to analyze the influence of anthocyanin extract of P. frutescens
      var. acuta on cell apoptosis. The results suggested that Perilla anthocyanins can
      induce Hela cell apoptosis by a dose dependent manner. 

PMID- 25996218
TI  - Evaluation of culture-based techniques and 454 pyrosequencing for the analysis of
      fungal diversity in potting media and organic fertilizers.
AB  - AIMS: Potting media and organic fertilizers (OFs) are commonly used in
      agricultural systems. However, there is a lack of studies on the efficiency of
      culture-based techniques in assessing the level of fungal diversity in these
      products. A study was conducted to investigate the efficiency of seven culture
      based techniques and pyrosequencing for characterizing fungal diversity in
      potting media and OFs. METHODS AND RESULTS: Fungal diversity was evaluated using
      serial dilution, direct plating and baiting with carrot slices, potato slices,
      radish seeds, cucumber seeds and cucumber cotyledons. Identity of all the
      isolates was confirmed on the basis of the internal transcribed spacer region of
      the ribosomal RNA (ITS rRNA) sequence data. The direct plating technique was
      found to be superior over other culture-based techniques in the number of fungal
      species detected. It was also found to be simple and the least time consuming
      technique. Comparing the efficiency of direct plating with 454 pyrosequencing
      revealed that pyrosequencing detected 12 and 15 times more fungal species from
      potting media and OFs respectively. Analysis revealed that there were differences
      between potting media and OFs in the dominant phyla, classes, orders, families,
      genera and species detected. Zygomycota (52%) and Chytridiomycota (60%) were the
      predominant phyla in potting media and OFs respectively. CONCLUSIONS: The
      superiority of pyrosequencing over cultural methods could be related to the
      ability to detect obligate fungi, slow growing fungi and fungi that exist at low
      population densities. SIGNIFICANCE AND IMPACT OF THE STUDY: The evaluated methods
      in this study, especially direct plating and pyrosequencing, may be used as tools
      to help detect and reduce movement of unwanted fungi between countries and
      regions.

PMID- 25996219
TI  - A comment on the statistical analyses and purported effects in Mohr et al.

PMID- 25996220
TI  - Response to the comment by Vigotsky.

PMID- 25996221
TI  - Scapular Kinematics During Late Cocking of a Simulated Throwing Activity in
      Baseball Players With Shoulder Injury: A Cross-Sectional Study Using a 3D-to-2D
      Registration Technique.
AB  - CONTEXT: Abnormal scapular kinematics during throwing motion in baseball players
      with shoulder disorders has not yet been clarified, although altered scapular
      position has been suggested to be associated with shoulder disorder. OBJECTIVE:
      To determine if the shoulders of baseball players with throwing disorders
      demonstrate abnormal scapular kinematics during the simulated arm-cocking phase
      of throwing activity. DESIGN: Cross-sectional study. SETTING: Laboratory.
      PARTICIPANTS: Eleven baseball players (age 21.1 +/- 1.2 y) with a unilateral
      shoulder disorder volunteered to participate, including 9 players at the college
      level and 2 at the adult level. The mean playing experience was 12.1 +/- 2.7 y.
      MAIN OUTCOME MEASURES: Scapular upward/downward rotation, anteroposterior
      tilting, and external/internal rotation during simulated arm-cocking motion were
      analyzed using a 3-to-2-dimensional registration technique. RESULTS: Scapular
      external rotation in the throwing shoulder was significantly smaller by 2.0-6.0
      degrees  than that of the contralateral shoulder. There were no detectable
      differences in scapular upward/downward rotation or anteroposterior tilting
      between the throwing and contralateral shoulders. CONCLUSIONS: Compared with that
      in the contralateral shoulder, scapular external rotation was smaller in the
      throwing shoulder, which would increase glenohumeral horizontal abduction during
      the arm-cocking phase and be related to the throwing-shoulder disorder.

PMID- 25996230
TI  - Does extreme leukocytosis predict serious bacterial infections in infants in the
      post-pneumococcal vaccine era? The experience of a large, tertiary care pediatric
      hospital.
AB  - BACKGROUND: Extreme leukocytosis, defined as a peripheral white blood cell count
      greater than 25,000/mm, may alarm clinicians and prompt extensive evaluation in
      infants with fever, especially in the pediatric emergency department. METHODS: We
      reviewed data from children aged 3 to 36 months with extreme leukocytosis, fever
      and the risk of serious bacterial infections (SBI) at our institution from July
      2010 to December 2012, a period after the universal introduction of pneumococcal
      vaccine. RESULTS: Serious bacterial infection was recorded in 57 (39%) of the 147
      infants. The most common SBI were segmental or lobar pneumonia, in 28 (19%)
      patients, and urinary tract infection in 16 (10.9%) patients. Three patients had
      positive blood cultures, corresponding to a bacteremia rate of 2%. C-reactive
      protein was significantly higher in the SBI group than in the non-SBI group.
      CONCLUSIONS: All well-looking febrile infants with white blood cell greater than
      25,000/mm should undergo a chest radiograph unless there are clear physical
      findings that indicate a different etiology. Urine culture should be considered
      in women. C-reactive protein can have an added value in the differential
      diagnosis.

PMID- 25996231
TI  - Creating a leaner pediatric emergency department: how rapid design and testing of
      a front-end model led to decreased wait time.
AB  - OBJECTIVE: To use Lean methodologies and the Model for Improvement to rapidly
      redesign and pilot test a new pediatric emergency department (ED) front-end model
      that reduces time to a licensed independent provider to 30 minutes or less.
      METHODS: Lean improvement methodologies were applied during a 5-day
      multidisciplinary model of care redesign event. The new ED front-end model of
      care included: (1) placement of a registered nurse in the lobby; (2) direct
      patient rooming with elimination of traditional triage; 3) early documentation of
      home medications; 4) Team-based immediate assessment; 5) "early Initiation"
      providers to place orders when a team was not available. An observational, cohort
      controlled before-and-after study design was used. The new model was tested over
      2 pilot periods and compared to a similar period of control days, defined as the
      "current state." RESULTS: The ED census and patient acuity were similar during
      both pilot periods. Eighteen patients were included in pilot 1, and 80 patients
      were included in the expanded second pilot. Patients seen within 30 minutes
      improved from a baseline of 33% to 93% in pilot 2. Time to a licensed independent
      provider, to a room, and to visual assessment by a nurse all decreased. The
      largest decrease was in median time to provider, from 43 minutes in the current
      state to 7 minutes during pilot 2. CONCLUSIONS: Rapid process improvement
      methodology was used to design and test a front-end model that reduced patient
      waiting time. Our experience demonstrates the feasibility of employing Lean
      principles and the Model for Improvement in actual practice environments to
      rapidly improve care delivery processes in pediatric emergency departments.

PMID- 25996232
TI  - Pediatric emergency department discharge prescriptions requiring pharmacy
      clarification.
AB  - OBJECTIVES: The aims of the study were to analyze and classify reasons why retail
      pharmacies need to contact the pediatric emergency department (PED) for
      clarification on outpatient prescriptions generated using an electronic
      prescribing system and to categorize the severity of errors captured. METHODS: A
      retrospective chart review was conducted at a PED that cares for approximately
      92,000 patients annually. All pharmacy callbacks documented in the electronic
      medical record between August 1, 2008 and July 31, 2009 were included. A
      datasheet was used to capture patient demographics (age, sex, race, insurance),
      prescriptions written, and reason for callback. Each call was then assigned a
      severity level, and time to respond to all calls was estimated. Frequencies were
      used to analyze the data. RESULTS: A total of 731 errors for 695 callbacks were
      analyzed from 49,583 prescriptions written at discharge. The most common errors
      included administrative/insurance issues 342/731 (47%) and prescription writing
      errors 298/731 (41%). The errors were classified as insignificant (340/729
      [47%]), problematic (288/729 [40%]), significant (77/729 [11%]), serious (12/729
      [1.64%]), and severe (12/729 [1.64%]). Almost 96% of errant prescriptions were
      not able to be filled as originally written and required a change by the
      prescriber. These calls required approximately 127 hours to complete.
      CONCLUSIONS: Prescription errors requiring a pharmacy callback are typically
      insignificant. However, 13.8% of callbacks about an error were considered
      significant, serious, or severe. Automated dose checking and verifying insurance
      coverage of prescribed medications should be considered essential components of
      prescription writing in a PED.

PMID- 25996233
TI  - Compliance of medications prescribed from a pediatric emergency department.
AB  - OBJECTIVES: Studies regarding compliance of medications prescribed from emergency
      departments (EDs) have primarily been adult-based or based on self-reported data.
      Most pediatric studies have shown that patients with private insurance tend to be
      more compliant. This study aims to determine the rate of medication compliance
      from a pediatric ED, which medications are most likely to be filled, if there are
      differences in compliance based on insurance status and age, and if noncompliant
      patients are more likely to have unintended return visits to the ED. METHODS: In
      this retrospective chart review, a sample of consecutive pediatric patients
      discharged from the ED was obtained. Pharmacies were contacted to ensure
      prescriptions were filled. Medication compliance was inferred if a prescription
      was filled. RESULTS: The 152 patients included had a total of 229 prescriptions
      that were used for data analysis. The overall medication compliance rate was
      72.5%. There was no statistically significant difference in medication compliance
      between age (P = 0.9), diagnosis (P = 0.26), insurance status (P = 0.3), or type
      of medication (P = 0.3). No difference was demonstrated for unintended return
      visits based on compliance (P = 0.79). CONCLUSIONS: Over a quarter of patients
      prescribed medications were noncompliant. However, there was no statistically
      significant difference in compliance between age, diagnosis, insurance status, or
      type of medication. Unlike most previous studies, privately insured patients were
      just as unlikely to fill their medications as publicly insured patients, and cost
      did not appear to be a contributing factor to noncompliance. Therefore efforts to
      educate patients and their families should be widespread and unbiased.

PMID- 25996234
TI  - Involvement of NtERF3 in the cell death signalling pathway mediated by SIPK/WIPK
      and WRKY1 in tobacco plants.
AB  - We previously reported that one of the ethylene response factors (ERFs), NtERF3,
      and other members of the subgroup VIII-a ERFs of the AP2/ERF family exhibit cell
      death-inducing ability in tobacco leaves. In this study, we focused on the
      involvement of NtERF3 in a cell death signalling pathway in tobacco plants,
      particularly downstream of NtSIPK/NtWIPK and NtWRKY1, which are mitogen-activated
      protein kinases and a phosphorylation substrate of NtSIPK, respectively. An ERF
      associated amphiphilic repression (EAR) motif-deficient NtERF3b mutant
      (NtERF3bDeltaEAR) that lacked cell death-inducing ability suppressed the
      induction of cell death caused by NtERF3a. The transient co-expression of
      NtERF3bDeltaEAR suppressed the hypersensitive reaction (HR)-like cell death
      induced by NtSIPK and NtWRKY1. The induction of cell death by NtSIPK and NtWRKY1
      was also inhibited in transgenic plants expressing NtERF3bDeltaEAR. Analysis of
      gene expression, ethylene production and cell death symptoms in salicylic acid
      deficient tobacco plants suggested the existence of some feedback regulation in
      the HR cell death signalling pathway mediated by SIPK/WIPK and WRKY1. Overall,
      these results suggest that NtERF3 functions downstream of NtSIPK/NtWIPK and
      NtWRKY1 in a cell death signalling pathway, with some feedback regulation. 

PMID- 25996236
TI  - On-chip optical mode conversion based on dynamic grating in photonic-phononic
      hybrid waveguide.
AB  - We present a scheme for reversible and tunable on-chip optical mode conversion
      based on dynamic grating in a hybrid photonic-phononic waveguide. The dynamic
      grating is built up through the acousto-optic effect and the theoretical model of
      the optical mode conversion is developed by considering the geometrical
      deformation and refractive index change. Three kinds of mode conversions are able
      to be realized using the same hybrid waveguide structure in a large bandwidth by
      only changing the launched acoustic frequency. The complete mode conversion can
      be achieved by choosing a proper acoustic power under a given waveguide length. 

PMID- 25996238
TI  - Bifunctional Ag@Pd-Ag Nanocubes for Highly Sensitive Monitoring of Catalytic
      Reactions by Surface-Enhanced Raman Spectroscopy.
AB  - We report a route to the facile synthesis of Ag@Pd-Ag nanocubes by cotitrating
      Na2PdCl4 and AgNO3 into an aqueous suspension of Ag nanocubes at room temperature
      in the presence of ascorbic acid and poly(vinylpyrrolidone). With an increase in
      the total titration volume, we observed the codeposition of Pd and Ag atoms onto
      the edges, corners, and side faces of the Ag nanocubes in a site-by-site fashion.
      By maneuvering the Pd/Ag ratio, we could optimize the SERS and catalytic
      activities of the Ag@Pd-Ag nanocubes for in situ SERS monitoring of the Pd
      catalyzed reduction of 4-nitrothiophenol by NaBH4. 

PMID- 25996237
TI  - Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes.
AB  - Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health
      burden worldwide, infecting over 750 million people leading to over 500,000
      deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS
      strains and multiple infection sites. To overcome fastidious genetic
      manipulations and accelerate pathogenesis investigations in GAS, we developed a
      mariner-based system (Krmit) for en masse monitoring of complex mutant pools by
      transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit
      insertions in ca. every 25 nucleotides) were generated in two distinct GAS
      clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic
      serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to
      predict GAS essential genes, identifying sets of 227 and 241 of those genes in
      5448 and NZ131, respectively. A large proportion of GAS essential genes
      corresponded to key cellular processes and metabolic pathways, and 177 were found
      conserved within the GAS core genome established from 20 available GAS genomes.
      Selected essential genes were validated using conditional-expression mutants.
      Finally, comparison to previous essentiality analyses in S. sanguinis and S.
      pneumoniae revealed significant overlaps, providing valuable insights for the
      development of new antimicrobials to treat infections by GAS and other pathogenic
      streptococci. 

PMID- 25996239
TI  - Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential
      Target for Treating Osteoporosis.
AB  - As human beings live longer, age-related diseases such as osteoporosis will
      become more prevalent. Intolerant side effects and poor responses to current
      treatments are observed. Therefore, novel effective therapeutic agents are
      greatly needed. Here, pyrazole derivatives were designed and synthesized, and
      their osteoclastogenesis inhibitory effects both in vitro and in vivo were
      evaluated. The most promising compound 13 with a 2-(dimethylamino)ethyl group
      inhibited markedly in vitro osteoclastogenesis as well as the bone resorption
      activity of osteoclasts. Compound 13 affected osteoclast's early proliferation
      and differentiation more than later fusion and maturation stages. In
      ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone
      volume, trabecular bone number, and trabecular thickness. Moreover, compound 13
      can antagonize OVX-induced reduction of serum bone resorption marker and then
      compensatory increase of the bone formation marker. To sum up, compound 13 has
      high potential to be developed into a novel therapeutic agent for treating
      osteoporosis in the future. 

PMID- 25996240
TI  - Low-current field-assisted assembly of copper nanoparticles for current
      collectors.
AB  - Current collectors are essential features of batteries and many other electronic
      devices being responsible for efficient charge transport to active electrode
      materials. Three-dimensional (3D), high surface area current collectors
      considerably improve the performance of cathodes and anodes in batteries, but
      their technological implementation is impeded by the complexity of their
      preparation, which needs to be simple, fast, and energy efficient. Here we
      demonstrate that field-stimulated assembly of ~3 nm copper nanoparticles (NPs)
      enables the preparation of porous Cu NP films. The use of NP dispersions enables
      30* reduction of the deposition current for making functional 3D coatings. In
      addition to high surface area, lattice-to-lattice connectivity in the self
      assembly of NPs in 3D structures enables fast charge transport. The mesoscale
      dimensions of out-of-plane features and the spacing between them in Cu films made
      by field-stimulated self-assembly of NPs provides promising morphology for
      current collection in lithium ion batteries (LIBs). Half-cell electrochemical
      models based on self-assembled films show improved specific capacity, total
      capacity, and cycling performance compared to traditional flat and other 3D
      current collectors. While integration of active electrode material into the 3D
      topography of the current collector needs to be improved, this study indicates
      that self-assembled NP films represent a viable manufacturing approach for 3D
      electrodes. 

PMID- 25996241
TI  - Structure and magnetic properties of an unusual homoleptic iron(III) thiocyanate
      dimer.
AB  - We describe the structural and variable temperature magnetic susceptibility
      properties of an unusual homoleptic bimetallic iron(III) thiocyanate tetraanion.
      This work represents the first structurally characterized bis(MU-1,3-thiocyanato)
      dimer of iron(III). A weak antiferromagnetic exchange interaction is observed
      between the two iron(III) ions, which is supported by broken symmetry density
      functional theory (DFT) calculations.

PMID- 25996242
TI  - Ruthenium-catalyzed oxidative coupling of 2-aryl-4-quinazolinones with olefins:
      synthesis of pyrrolo[2,1-b]quinazolin-9(1H)-one motifs.
AB  - A ruthenium-catalyzed oxidative coupling of 2-aryl-quinazolinones with olefins
      via C-H bond activation followed by an intramolecular aza-Michael reaction is
      described. This strategy allows the direct and efficient construction of
      pyrrolo[2,1-b]quinazolin-9(1H)-one scaffolds. 

PMID- 25996243
TI  - Rejoinder to "A note on the empirical likelihood confidence band for hazards
      ratio with covariate adjustment".

PMID- 25996244
TI  - Large Energy Storage Density and High Thermal Stability in a Highly Textured
      (111)-Oriented Pb0.8Ba0.2ZrO3 Relaxor Thin Film with the Coexistence of
      Antiferroelectric and Ferroelectric Phases.
AB  - A highly textured (111)-oriented Pb0.8Ba0.2ZrO3 (PBZ) relaxor thin film with the
      coexistence of antiferroelectric (AFE) and ferroelectric (FE) phases was prepared
      on a Pt/TiOx/SiO2/Si(100) substrate by using a sol-gel method. A large
      recoverable energy storage density of 40.18 J/cm(3) along with an efficiency of
      64.1% was achieved at room temperature. Over a wide temperature range of 250 K
      (from room temperature to 523 K), the variation of the energy density is within
      5%, indicating a high thermal stability. The high energy storage performance was
      endowed by a large dielectric breakdown strength, great relaxor dispersion,
      highly textured orientation, and the coexistence of FE and AFE phases. The PBZ
      thin film is believed to be an attractive material for applications in energy
      storage systems over a wide temperature range. 

PMID- 25996245
TI  - Trends in advanced computed tomography use for injured patients in United States
      emergency departments: 2007-2010.
AB  - OBJECTIVES: Studies have documented increased advanced radiography use in U.S.
      emergency departments (EDs) for injured patients over the past decade. The
      authors explored trends in recent years (2007 through 2010) in advanced
      radiography use, specifically head computed tomography (CT) and nonhead CT scans.
      METHODS: This was a retrospective analysis of ED visits conducted using data from
      the National Hospital Ambulatory Medical Care Survey (NHAMCS), a representative
      sample of the U.S. ED visits from 2007 through 2010. All patients designated by
      the NHAMCS as "related to injury" were included in analyses. CT use was examined
      by head and nonhead use. Trends, predictors of utilization, and diagnostic yield
      for head and nonhead CT scans in injured ED patients were analyzed using survey
      weighted logistic regression. Diagnostic yield was defined as the proportion of
      injury-related visits where patients imaged with CT received International
      Classification of Diseases, 9th Revision (ICD-9), code diagnoses of a severe head
      or nonhead injury. RESULTS: Among injured ED patients, head CT use increased from
      9.6% in 2007 to 11.6%, a relative increase of 20.8% (p < 0.001), and nonhead CT
      from 5.5% to 7.3%, a relative increase of 47.3% (p < 0.001). Diagnostic yield for
      head CT was unchanged (4.9% in 2007 vs. 3.4% in 2010, p = 0.093), but fell for
      nonhead CT from 6.4% in 2007 to 3.3% in 2010 (p = 0.04. CONCLUSIONS: Advanced
      radiography use has continued to increase since 2007 in injured patients, and
      diagnostic yield for nonhead CT has continued to fall. Head CT is more common
      than CTs of other body areas and may represent an opportunity for reduction given
      validated clinical decision rules.

PMID- 25996246
TI  - Dangling OH Vibrations of Water Molecules in Aqueous Solutions of Aprotic Polar
      Compounds Observed in the Near-Infrared Regime.
AB  - Near-infrared (NIR) absorption spectrum measurements over a frequency range from
      4000 to 12000 cm(-1) were employed to investigate the effects of the presence of
      solute compounds to vibrational modes of water molecules in aqueous solutions of
      some aprotic hydroneutral polar compounds with large dipole moments, such as
      nitro compounds and nitriles. The obtained NIR spectra for the aqueous solutions
      were decomposed into three components: free water, solute, and water molecules
      affected by the presence of solutes. Newly determined NIR spectra of affected
      water molecules were well-described with at least four absorption modes observed
      at 7040, 6850, 6450, and 5640 cm(-1) for both the nitro compounds and nitriles.
      The highest frequency mode at 7040 cm(-1) possessing the strongest intensity was
      assigned to the first stretching overtone of affected water hydroxy (O-H) groups,
      which are nonhydrogen bonded to other water molecules and dangling. The second
      highest frequency mode at 6850 cm(-1) was assigned to the first stretching
      overtone of affected water O-H groups hydrated to other (free) water molecules.
      The third mode at 6400 cm(-1) was attributed to a combination mode of the
      fundamental stretching of O-H and the first overtone of the O-H bending mode of
      the affected water molecules. The lowest frequency mode at 5640 cm(-1) was
      assigned to the combination mode of the fundamental O-H stretching mode, the
      fundamental O-H bending mode, and the hindered rotational (libration) mode of the
      affected water molecules. Because absorption intensities of the third and lowest
      frequency modes for water molecules affected by the solutes depended on the sizes
      of alkyl groups of polar solutes, these two modes possibly result from the
      contribution of hydrophobic hydration effects. 

PMID- 25996247
TI  - Long-term follow-up study of porcine anti-human thymocyte immunoglobulin therapy
      combined with cyclosporine for severe aplastic anemia.
AB  - Immunosuppressive therapy with antithymocyte immunoglobulin (ATG) and
      cyclosporine A is the first treatment option for severe aplastic anemia (SAA)
      patients without transplantation. Horse ATG is not marketed in China. Because the
      price of porcine ATG (pATG) is only about one-third of the price of rabbit ATG
      (rATG), long-term follow-up studies of pATG's efficacy will help provide valuable
      insights into the treatment of SAA. Retrospective studies were performed to
      analyze the clinical information of 102 SAA patients treated with pATG and
      cyclosporine A from 1999 to 2014 in Peking Union Medical College Hospital. The
      median age was 29 years old (range 12-72). Median follow-up time was 59.6 months
      (0.2-176.8). The overall response rate was 74.5% (CR 42.1%, PR 32.4%). The
      recurrence rate was 9.9%. The mortality rate was 16.7%. The median survival time
      has not been reached, and the 5-year survival rate was 81.8%. Other hematologic
      abnormalities were observed in 7.8% of patients, including symptomatic PNH, MDS,
      and AML. Multivariate analysis revealed there was no significant effect on
      survival by factors such as gender, age, severity of disease, treatment time, and
      PNH clone (P > 0.05). These data have indicated pATG therapy combined with
      cyclosporine A has significant long-term efficacy and high overall survival in
      SAA.

PMID- 25996248
TI  - Silver nanowire interactions with primary human alveolar type-II epithelial cell
      secretions: contrasting bioreactivity with human alveolar type-I and type-II
      epithelial cells.
AB  - Inhaled nanoparticles have a high deposition rate in the alveolar units of the
      deep lung. The alveolar epithelium is composed of type-I and type-II epithelial
      cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The
      effect of native human ATII cell secretions on nanoparticle toxicity is not
      known. We investigated the cellular uptake and toxicity of silver nanowires
      (AgNWs; 70 nm diameter, 1.5 MUm length) with human ATI-like cells (TT1), in the
      absence or presence of Curosurf(r) (a natural porcine pulmonary surfactant with a
      low amount of protein) or harvested primary human ATII cell secretions (HAS;
      containing both the complete lipid as well as the full protein complement of
      human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that
      Curosurf(r) or HAS would confer improved protection for TT1 cells, limiting the
      toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory
      and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1
      cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%,
      respectively, resulting in similar levels to that of the non-treated controls.
      However in contrast to our hypothesis, Curosurf(r) had no effect. We found a
      significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not
      Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved
      in this process as they were found to be specifically bound to the AgNWs. While
      ATI cells appear to be protected by HAS, evidence suggested that ATII cells,
      despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8
      release and ROS generation and decreased intracellular SP-A levels one day post
      exposure). This study provides unique findings that may be important for the
      study of lung epithelial-endothelial translocation of nanoparticles in general
      and associated toxicity within the alveolar unit. 

PMID- 25996249
TI  - Research highlights: manipulating cells inside and out.
AB  - We highlight recent work manipulating cells: from whole cells, to intracellular
      content, and even subcellular gradients in proteins. In the first manuscript,
      using interdigitated electrode arrays at a controlled tilt angle to a
      microchannel allows for an array of acoustic nodes that apply force and isolate
      larger circulating tumor cells from remaining cells in RBC-lysed blood. Moving to
      the subcellular scale, recent work shows the ability to use rapid bubble
      generation induced by a pulsed laser to transfect hundreds of thousands of cells
      in parallel, especially with larger cargo, such as live bacteria. Manipulating at
      an even finer level, our third highlighted paper applies magnetic nanoparticle
      based techniques to the localization of proteins within the cytoplasm in gradient
      configurations. A recurring theme in the literature is how interfacing at the
      cellular scale is a key feature enabled by micro & nanotechnology. This feature
      can be exploited to achieve new capabilities for cell biologists which opens up
      new fundamental cell biology questions. This matching of scales and the unique
      advantages are well demonstrated in the articles highlighted. 

PMID- 25996250
TI  - MALT1--a universal soldier: multiple strategies to ensure NF-kappaB activation
      and target gene expression.
AB  - The paracaspase MALT1 (mucosa associated lymphoid tissue lymphoma translocation
      gene 1) is an intracellular signaling protein that plays a key role in innate and
      adaptive immunity. It is essential for nuclear factor kappaB (NF-kappaB)
      activation and proinflammatory gene expression downstream of several cell surface
      receptors. MALT1 has been most studied in the context of T-cell receptor-induced
      NF-kappaB signaling, supporting T-cell activation and proliferation. In addition,
      MALT1 hyperactivation is associated with specific subtypes of B-cell lymphoma,
      where it controls tumor cell proliferation and survival. For a long time, MALT1
      was believed to function solely as a scaffold protein, providing a platform for
      the assembly of other NF-kappaB signaling proteins. However, this view changed
      dramatically when MALT1 was found to have proteolytic activity that further fine
      tunes signaling. MALT1 proteolytic activity is essential for T-cell activation
      and lymphomagenesis, suggesting that MALT1 is a promising therapeutic target for
      the treatment of autoimmune diseases and distinct lymphoma entities. However,
      interference with MALT1 activity may pose a dangerous threat to the normal
      functioning of the immune system and should be evaluated with great care. Here we
      discuss the current knowledge on the scaffold and protease functions of MALT1,
      including an overview of its substrates and the functional implications of their
      cleavage. 

PMID- 25996251
TI  - On the use of the transmission disequilibrium test to detect pseudo-autosomal
      variants affecting traits with sex-limited expression.
AB  - We herein describe the realization of a genome-wide association study for scrotal
      hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We
      have used the transmission disequilibrium test to avoid spurious associations due
      to population stratification. By doing so, we obtained genome-wide significant
      signals for both diseases with SNPs located in the pseudo-autosomal region in the
      vicinity of the pseudo-autosomal boundary. By further analyzing these signals, we
      demonstrate that the observed transmission disequilibria are artifactual. We
      determine that transmission bias at pseudo-autosomal markers will occur (i) when
      analyzing traits with sex-limited expression and (ii) when the allelic
      frequencies at the marker locus differ between X and Y chromosomes. We show that
      the bias is due to the fact that (i) sires will preferentially transmit the
      allele enriched on the Y (respectively X) chromosome to affected sons
      (respectively daughters) and (ii) dams will appear to preferentially transmit the
      allele enriched on the Y (respectively X) to affected sons (respectively
      daughters), as offspring inheriting the other allele are more likely to be non
      informative. We define the conditions to mitigate these issues, namely by (i)
      extracting information from maternal meiosis only and (ii) ignoring trios for
      which sire and dam have the same heterozygous genotype. We show that by applying
      these rules to scrotal hernia and cryptorchidism, the pseudo-autosomal signals
      disappear, confirming their spurious nature. 

PMID- 25996252
TI  - Should be there specific guidelines to improve reporting of clinical pharmacology
      trials?

PMID- 25996253
TI  - Survey of coagulation factor concentrates tender and procurement procedures in 38
      European Countries.
AB  - INTRODUCTION: Procurement of coagulation factor concentrates (CFCs) for the
      treatment of haemophilia is a vital process that determines the quantity and
      quality of factor replacement therapy. AIM: The aim of this study was to examine
      the different tender and procurement systems used in Europe for the procurement
      of CFCs and the outcomes produced by the various systems. METHODS: The survey
      questionnaire consisted of 30 items and explored various aspects of the
      procurement process including the prices of CFCs. In 2014, the survey was sent
      out by the European Haemophilia Consortium (EHC) to 45 national haemophilia
      patient organizations affiliated to the EHC in all European countries as well as
      to a designated clinician familiar with the procurement process. RESULTS: The
      survey was completed by 38 European countries. Nineteen countries use a tender
      process, 17 an alternative procurement process and 2 use a combination of
      methods. A wide variety of agencies and individuals are involved in the process.
      Factors associated with optimum outcome and lower prices include a tender process
      with a specific legal framework and a tender board including haemophilia
      clinicians and patient organization representatives. Safety was reported as the
      most important selection criterion but given the safety profile of almost all
      currently licensed products, price was the main criterion used in many countries.
      CONCLUSION: The involvement of both clinicians and patient organizations greatly
      improves the outcome of a tender or procurement process, as does the presence of
      a legal framework that governs the process.

PMID- 25996254
TI  - Initial O2 Insertion Step of the Tryptophan Dioxygenase Reaction Proposed by a
      Heme-Modification Study.
AB  - L-Tryptophan 2,3-dioxygenase (TDO) is a protoheme-containing enzyme that
      catalyzes the production of N-formylkynurenine by inserting O2 into the pyrrole
      ring of L-tryptophan. Although a ferrous-oxy form (Fe2+-O2) has been established
      to be an obligate intermediate in the reaction, details of the ring opening
      reaction remain elusive. In this study, the O2 insertion reaction catalyzed by
      Pseudomonas TDO (PaTDO) was examined using a heme-modification approach, which
      allowed us to draw a quantitative correlation between the inductive electronic
      effects of the heme substituents and the substituent-induced changes in the
      functional behaviors of the ferrous-oxy form. We succeeded in preparing
      reconstituted PaTDO with synthetic hemes, which were different with respect to
      the inductive electron-withdrawing nature of the heme substituents at positions 2
      and 4. An increase in the electron-withdrawing power of the heme substituents
      elevated the redox potential of reconstituted PaTDO, showing that the stronger
      the electron-withdrawing ability of the heme substituents, the lower the electron
      density on the heme iron. The decrease in the electron density of the heme iron
      resulted in a higher frequency shift of the C-O stretch of the heme-bound CO and
      enhanced the dissociation of O2 from the ferrous-oxy intermediate. This result
      was interpreted as being due to weaker pi back-donation from the heme iron to the
      bound CO or O2. More importantly, the reaction rates of the ferrous-oxy
      intermediate to oxidize L-Trp were increased with the electron-withdrawing
      ability of the heme substituents, implying that the more electron-deficient
      ferrous-oxy heme is favored for the PaTDO-catalyzed oxygenation. On the basis of
      these results, we propose that the initial step of the dioxygen activation by
      PaTDO is a direct electrophilic addition of the heme-bound O2 to the indole ring
      of L-Trp.

PMID- 25996255
TI  - Impact of a Multifaceted Intervention on Promoting Adherence to Screening
      Colonoscopy Among Persons in HIV Primary Care: A Pilot Study.
AB  - HIV-positive patients have lower colon cancer screening rates and are at
      increased risk for colon adenocarcinoma. We tested a transdisciplinary prevention
      model to increase provider and patient adherence to screening colonoscopy. Of
      1,339 HIV-positive patients with scheduled clinic appointments during the period
      September to November 2009, we identified 400 records of eligible patients >=50
      years and retrospectively reviewed for screening colonoscopy referral; if never
      referred, flagged for referral at next visit. Providers referred 43.5% (174/400)
      patients and 36.2% (63/174) kept appointment. Within 6 months before the study,
      337 patients attended clinic and providers referred 18%. Note that 211/226
      patients with flagged records attended clinic at least once during the study 6
      month period and providers referred (43.6%). The referral rate for flagged
      records was significantly different from that for the prior 6 months (p <
      0.0001). A randomized trial compared the efficacy of patient decision support
      versus usual care on screening adherence. Among patients randomized to
      intervention 17 (51.5%) compared to usual care only 16 (48.5%), intervention
      group showed significant adherence of 70.6% (12/17) versus 29.4% (5/16), (p =
      0.024). In addition, intervention patients had good bowel preparation of 76.9%
      (10/13) versus usual care 23.1% (3/13), (p = 0.05). This transdisciplinary
      intervention model significantly increased provider and patient screening
      colonoscopy behavior. 

PMID- 25996257
TI  - Retraction. Updated Knowledge about Polyphenols: Functions, Bioavailability,
      Metabolism, and Health.

PMID- 25996256
TI  - Monoamine oxidases are novel sources of cardiovascular oxidative stress in
      experimental diabetes.
AB  - Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease
      associated with increased cardiovascular morbidity and mortality. The generation
      of reactive oxygen species (ROS) is a major event causally linked to the
      development of cardiovascular complications throughout the evolution of DM.
      Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2
      isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen
      peroxide (H2O2) production in the cardiovascular system via the oxidative
      deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators
      of endothelial dysfunction in DM is unknown, and so we studied this in a
      streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein)
      was increased in both arterial samples and hearts isolated from the diabetic
      animals. Also, H2O2 production (ferrous oxidation - xylenol orange assay) in
      aortic samples was significantly increased, together with an impairment of
      endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline
      and selegiline) attenuated ROS production by 50% and partially normalized the
      endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in
      particular the MAO-B isoform, are induced in aortas and hearts in the
      streptozotocin-induced diabetic rat model and contribute, via the generation of
      H2O2, to the endothelial dysfunction associated with experimental diabetes. 

PMID- 25996258
TI  - Up-regulation of Bcl-2 by CD147 Through ERK Activation Results in Abnormal Cell
      Survival in Human Endometriosis.
AB  - CONTEXT: Human endometriosis (EMS) is characterized by insufficient apoptosis.
      Our previous studies have shown elevated CD147 expression in human endometriotic
      tissues and its involvement in endometrial cell apoptosis. However, the exact
      underlying mechanism remains elusive. OBJECTIVE: The objective was to examine the
      correlation of the highly expressed CD147 with anti-apoptotic factor Bcl-2 in
      human endometriotic tissues and to determine the CD147-regulated apoptotic
      pathway in human endometrial epithelial cell line (HES). DESIGN: This was a
      laboratory study using human tissue analysis and HES cell culture. SETTING: The
      setting was an academic research center and hospital. PATIENTS: Patients were 30
      women with ovarian EMS and 12 women without EMS. INTERVENTIONS: mRNA levels of
      CD147 and Bcl-2 were evaluated in endometriotic tissues by quantitative real-time
      PCR. HES cells were transfected with pcDNA3.0-CD147 overexpressing plasmid or
      immune-depleted by CD147 antibody. MAIN OUTCOME MEASURES: Main outcome measures
      were reverse transcription, quantitative real-time PCR, 3-(4,5-dimethylthiazol-2
      yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and
      Western blotting. RESULTS: In human endometriotic tissues, Bcl-2 was up-regulated
      and positively correlated with CD147 expression, accompanied by activated ERK
      signaling. In HES cells, overexpression of CD147 increased viable cells and up
      regulated Bcl-2 expression by activation of ERK signaling. Interference with
      CD147 function suppressed ERK signaling and decreased Bcl-2 expression, followed
      by accumulation of apoptotic factors, including cleaved caspase-9, cleaved
      caspase-3, and cleaved poly ADP-ribose polymerase. CONCLUSIONS: The presently
      found strong correlations between Bcl-2 and CD147, ERK, and CD147 in human
      endometriotic lesions and the demonstrated reduced cell apoptosis through CD147
      ERK-Bcl-2 intrinsic apoptosis signaling axis suggest that this CD147-regulated
      signaling may contribute to the enhanced cell survival in the progression of
      human EMS.

PMID- 25996259
TI  - Eligibility for the Subcutaneous Implantable Cardioverter-Defibrillator in
      Patients With Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: High-risk hypertrophic cardiomyopathy (HCM) patients benefit from the
      implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) may
      provide comparable protection while avoiding the shortcomings of transvenous (TV)
      leads. We assessed S-ICD eligibility according to surface ECG screening test in a
      cohort of high-risk HCM patients. METHODS AND RESULTS: 47 HCM patients (3 S-ICD
      candidates; 41 TV-ICD patients without pacing indication; and 3 pacemaker
      dependent TV-ICD patients) underwent 4 screening protocols: standard (n = 44);
      exercise (n = 33); continuous pacing (n = 44); alternating paced/spontaneous QRS
      (n = 41). Of the 44 patients in the standard screening group, 41 (93%) were
      eligible. Max LV thickness was inversely related to the number of qualifying
      leads (3 leads: 21 +/- 4 mm; 2 leads: 22 +/- 6 mm; 1 lead: 25 +/- 6 mm; no leads:
      28 +/- 11 mm; P = 0.07). Of the 33 patients in the exercise group, 5 were
      ineligible (3 after exercise). Of these, 2 became eligible after moving sternal
      electrodes from the left to the right parasternal line (eligibility rate: 30/33;
      91%). Of the 44 patients in the continuous pacing group, 28 (64%) were eligible,
      8 of which with right parasternal electrodes. In the paced/spontaneous QRS group
      (n = 41), 21 patients (51%) had at least 1 eligible lead during pacing and
      retained compatibility on the same lead during spontaneous rhythm, 5 of which
      with right parasternal electrodes. CONCLUSIONS: S-ICD screening failure is low in
      HCM, provided that patients with severe hypertrophy are carefully evaluated.
      Exercise test should be performed and right parasternal leads tested. Pacemaker
      patients display lower eligibility rate.

PMID- 25996260
TI  - Characterization of an age-response relationship to GSK's recombinant hepatitis B
      vaccine in healthy adults: An integrated analysis.
AB  - The immune system becomes less effective with age, and older age is associated
      with an increased susceptibility to diseases and reduced responses to
      vaccination. Furthermore, some adult populations, such as those with diabetes
      mellitus, are at increased risk of acute hepatitis B virus (HBV) infection.
      Decreasing responses to vaccination with advanced age have been described, but it
      is not known at what age immunogenicity starts to reduce, or until what age
      immunogenicity remains acceptable (for example >= 80% seroprotection post
      vaccination). We characterized the relationship between age and seroprotection
      rate induced by recombinant HBV vaccination by conducting a pooled analysis of
      clinical trial data. Healthy adults aged >= 20 y who had been vaccinated with 20
      MUg HBV vaccine (EngerixTM B, GSK Vaccines, Belgium) in a 0, 1, 6 months schedule
      in 11 studies since 1996 were included. The observed seroprotection rate, defined
      as an anti-HBV surface antigen antibody concentration >= 10 mIU/ml was 94.5% in
      the whole population (N = 2,620, Total vaccinated cohort), ranging from 98.6% in
      adults vaccinated at age 20-24 years, to 64.8% in those vaccinated at age >= 65 y
      A model on seroprotection rates showed a statistically significant decrease with
      age, and predicted that the anti-HBs seroprotection rate remains >= 90% up to 49
      y of age and >= 80% up to 60 y of age. Individuals at risk of HBV infection
      should be vaccinated as early in life as possible to improve the likelihood of
      achieving seroprotection. Additional studies are needed to identify whether
      unvaccinated individuals older than 60 y would benefit from regimens that include
      additional or higher vaccine doses.

PMID- 25996261
TI  - Feasibility and Acceptability of a Text Messaging Program for Smoking Cessation
      in Israel.
AB  - Text messaging programs on mobile phones have been shown to promote smoking
      cessation. This study investigated whether a text-messaging program for smoking
      cessation, adapted from QuitNowTXT, is feasible in Israel and acceptable to
      Israeli smokers. Participants (N = 38) were given a baseline assessment, enrolled
      in the adapted text messaging program, and followed-up with at 2 weeks and 4
      weeks after their quit date. The authors used an intent-to-treat analysis and
      found that 23.7% of participants reported having quit smoking at the 4-week
      follow-up. Participants sent an average of 12.9 text replies during the study
      period, and the majority reported reading most or all of the texts. However,
      34.2% of participants had unsubscribed by the 4-week follow-up. Moderate levels
      of satisfaction were reported; more than half agreed that they would recommend
      the program. Suggestions for improvement included adding advice by an expert
      counselor, website support, and increased customization. Results indicate that a
      text messaging smoking cessation program developed by modifying the content of
      QuitNowTXT is feasible and could be acceptable to smokers in Israel. The
      experience adapting and pilot testing the program can serve as a model for using
      QuitNowTXT to develop and implement such programs in other countries. 

PMID- 25996262
TI  - Phyllanthus spp. Exerts Anti-Angiogenic and Anti-Metastatic Effects Through
      Inhibition on Matrix Metalloproteinase Enzymes.
AB  - Tumor angiogenesis and metastasis are the major causes for high morbidity and
      mortality rates in cancer patient. Modulation on tumor angiogenesis and
      metastasis provides opportunities to halt progression of cancer. From our
      previous findings, Phyllanthus plant possesses antiproliferative effects on
      melanoma and prostate cancer cell lines and induction of apoptosis. The main aims
      of the present work were further investigated on the antimetastatic and
      antiangiogenic effects on cancer cells (MeWo and PC-3) and human umbilical vein
      endothelial cells (HUVECs) of 4 Phyllanthus species (P.amarus, P.niruri,
      P.urinaria and P.watsonii). Phyllanthus extracts significantly inhibited cell
      adhesion, migration, invasion, and transendothelial migration activities of
      cancer (MeWo and PC-3) cells in a dose-dependent manner (P < 0.05) by cell-matrix
      adhesion, Transwell migration, invasion, and transendothelial migration assays.
      Phyllanthus extracts were exhibited low cytotoxicity on HUVECs up to a
      concentration of 500.0 MUg/ml by MTS reduction assay. Phyllanthus extracts also
      exhibited antiangiogenic effects through inhibition of migration, invasion, and
      microcapillary like-tube structure formation in HUVECs. These observations were
      due to alteration in activities of matrix metalloproteinase (MMP) -2, -7, -9, and
      -26 in treated-endothelial and cancer cells by zymographies. These findings
      suggest that Phyllanthus plant has the potential to inhibit tumour metastasis and
      angiogenesis through the suppression of MMP enzymes. 

PMID- 25996266
TI  - Regular transcutaneous myostimulation alters skeletal muscle phospholipid fatty
      acid composition and oxidative stability in rabbits.

PMID- 25996267
TI  - Single, double and multi cough sound differentiation.

PMID- 25996265
TI  - Cell infiltration into a 3D electrospun fiber and hydrogel hybrid scaffold
      implanted in the brain.
AB  - Tissue engineering scaffolds are often designed without appropriate consideration
      for the translational potential of the material. Solid scaffolds implanted into
      central nervous system (CNS) tissue to promote regeneration may require tissue
      resection to accommodate implantation. Or alternatively, the solid scaffold may
      be cut or shaped to better fit an irregular injury geometry, but some features of
      the augmented scaffold may fail to integreate with surrounding tissue reducing
      regeneration potential. To create a biomaterial able to completely fill the
      irregular geometry of CNS injury and yet still provide sufficient cell migratory
      cues, an injectable, hybrid scaffold was created to present the physical
      architecture of electrospun fibers in an agarose/methylcellulose hydrogel. When
      injected into the rat striatum, infiltrating macrophages/microglia and resident
      astrocytes are able to locate the fibers and utilize their cues for migration
      into the hybrid matrix. Thus, hydrogels containing electrospun fibers may be an
      appropriate platform to encourage regeneration of the injured brain. 

PMID- 25996268
TI  - Effect of intermittent hypoxia on pro- and antioxidant balance in rat heart
      during high-intensity chronic exercise.
AB  - The purpose of the present study was to elucidate the influence of sessions of
      intermittent hypoxic training (IHT) alone and in combination with high-intensity
      chronic exercise on lipid peroxidation and antioxidative defense system in rat
      heart. High-intensity chronic exercise was performed as swimming training with
      load that corresponded to ~ 75% VO2max(30 min/day, 5 days/wk, for 4 wk). IHT
      consisted of repeated episodes of hypoxia (12% O2, 15 min), interrupted by equal
      periods of recovery (5 sessions/day, for 2wk). Sessions of IHT were applied
      during the first two weeks and during the last two weeks of chronic exercise. It
      was shown that long-term training was accompanied by the accumulation of
      thiobarbituric acid reactive substances (TBARS) in myocardium. IHT attenuated the
      increase in TBARS content caused by high-intensity chronic exercise and it
      enhanced myocardial reduced glutathione concentration, activities of superoxide
      dismutase, catalase, and glutathione peroxidase in comparison with trained
      animals only. No significant changes were found in glutathione reductase, glucose
      6-phosphate dehydrogenase activities. Our results suggest that intermittent
      hypoxic stimuli may induce a state of preconditioning that protects the heart
      from oxidative stress evoked by high-intensity chronic exercise.

PMID- 25996270
TI  - Report on the 15th IAA Humans in Space Symposium 2005 in Austria.

PMID- 25996269
TI  - The effect of acute creatinine monohydrate loading on wingate test results in 18
      21 years old male soccer players.

PMID- 25996271
TI  - LXIXth Annual Meeting of the Hungarian Physiological Society.

PMID- 25996272
TI  - 6th International Congress of the Worldwide Hungarian Medical Academy (WHMA).

PMID- 25996277
TI  - Post-rib harvesting pain should be considered as a potential significant
      morbidity in reconstructive rhinoplasty.

PMID- 25996278
TI  - The art of local anesthesia surgery.

PMID- 25996274
TI  - Cannabis Smoking in 2015: A Concern for Lung Health?
AB  - Recent legislative successes allowing expanded access to recreational and
      medicinal cannabis have been associated with its increased use by the public,
      despite continued debates regarding its safety within the medical and scientific
      communities. Despite legislative changes, cannabis is most commonly used by
      smoking, although alternatives to inhalation have also emerged. Moreover, the
      composition of commercially available cannabis has dramatically changed in recent
      years. Therefore, developing sound scientific information regarding its impact on
      lung health is imperative, particularly because published data conducted prior to
      widespread legalization are conflicting and inconclusive. In this commentary, we
      delineate major observations of epidemiologic investigations examining cannabis
      use and the potential associated development of airways disease and lung cancer
      to highlight gaps in pulmonary knowledge. Additionally, we review major
      histopathologic alterations related to smoked cannabis and define specific areas
      in animal models and human clinical translational investigations that could
      benefit from additional development. Given that cannabis has an ongoing
      classification as a schedule I medication, federal funding to support
      investigations of modern cannabis use in terms of medicinal efficacy and safety
      profile on lung health have been elusive. It is clear, however, that the effects
      of inhaled cannabis on lung health remain uncertain and given increasing use
      patterns, are worthy of further investigation. 

PMID- 25996280
TI  - Error in abstract.

PMID- 25996279
TI  - Post-Rib Harvesting Pain Should be Considered as a Potential Significant
      Morbidity in Reconstructive Rhinoplasty-Reply.

PMID- 25996283
TI  - EGFR promoter exhibits dynamic histone modifications and binding of ASH2L and
      P300 in human germinal matrix and gliomas.
AB  - Several signaling pathways important for the proliferation and growth of brain
      cells are pathologically dysregulated in gliomas, including the epidermal growth
      factor receptor (EGFR). Expression of EGFR is high in neural progenitors during
      development and in gliomas but decreases significantly in most adult brain
      regions. Here we show that EGFR expression is maintained in the astrocyte ribbon
      of the adult human subventricular zone. The transcriptional regulation of EGFR
      expression is poorly understood. To investigate the role of epigenetics on EGFR
      regulation in the contexts of neural development and gliomagenesis, we measured
      levels of DNA methylation and histone H3 modifications at the EGFR promoter in
      human brain tissues, glioma specimens, and EGFR-expressing neural cells, acutely
      isolated from their native niche. While DNA was constitutively hypomethylated in
      non-neoplastic and glioma samples, regardless of their EGFR-expression status,
      the activating histone modifications H3K27ac and H3K4me3 were enriched only when
      EGFR is highly expressed (developing germinal matrix and gliomas). Conversely,
      repressive H3K27me3 marks predominated in adult white matter where EGFR is
      repressed. Furthermore, the histone methyltransferase core enzyme ASH2L was bound
      at EGFR in the germinal matrix and in gliomas where levels of H3K4me3 are high,
      and the histone acetyltransferase P300 was bound in samples with H3K27ac
      enrichment. Our studies use human cells and tissues undisturbed by cell-culture
      artifact, and point to an important, locus-specific role for chromatin remodeling
      in EGFR expression in human neural development that may be dysregulated during
      gliomagenesis, unraveling potential novel targets for future drug therapy. 

PMID- 25996284
TI  - Sustained accumulation of prelamin A and depletion of lamin A/C both cause
      oxidative stress and mitochondrial dysfunction but induce different cell fates.
AB  - The cell nucleus is structurally and functionally organized by lamins,
      intermediate filament proteins that form the nuclear lamina. Point mutations in
      genes that encode a specific subset of lamins, the A-type lamins, cause a
      spectrum of diseases termed laminopathies. Recent evidence points to a role for A
      type lamins in intracellular redox homeostasis. To determine whether lamin A/C
      depletion and prelamin A accumulation differentially induce oxidative stress, we
      have performed a quantitative microscopy-based analysis of reactive oxygen
      species (ROS) levels and mitochondrial membrane potential (Deltapsim) in human
      fibroblasts subjected to sustained siRNA-mediated knockdown of LMNA and ZMPSTE24,
      respectively. We measured a highly significant increase in basal ROS levels and
      an even more prominent rise of induced ROS levels in lamin A/C depleted cells,
      eventually resulting in Deltapsim hyperpolarization and apoptosis. Depletion of
      ZMPSTE24 on the other hand, triggered a senescence pathway that was associated
      with moderately increased ROS levels and a transient Deltapsim depolarization.
      Both knockdowns were accompanied by an upregulation of several ROS detoxifying
      enzymes. Taken together, our data suggest that both persistent prelamin A
      accumulation and lamin A/C depletion elevate ROS levels, but to a different
      extent and with different effects on cell fate. This may contribute to the
      variety of disease phenotypes witnessed in laminopathies. 

PMID- 25996285
TI  - Improved blood biomarkers but no cognitive effects from 16 weeks of multivitamin
      supplementation in healthy older adults.
AB  - Supplementation with vitamins, minerals and phytonutrients may be beneficial for
      cognition, especially in older adults. The aim of this study was to assess the
      effects of multivitamin supplementation in older adults on cognitive function and
      associated blood biomarkers. In a randomised, double blind, placebo-controlled
      trial, healthy women (n = 68) and men (n = 48) aged 55-65 years were supplemented
      daily for 16 weeks with women's and men's formula multivitamin supplements.
      Assessments at baseline and post-supplementation included computerised cognitive
      tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements
      were observed after supplementation with either formula; however, several
      significant improvements were observed in blood biomarkers including increased
      levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in
      women; reduced homocysteine and marginally reduced oxidative stress in men; as
      well as improvements to the lipid profile in men. In healthy older people,
      multivitamin supplementation improved a number of blood biomarkers that are
      relevant to cognition, but these biomarker changes were not accompanied by
      improved cognitive function. 

PMID- 25996286
TI  - Chemical Composition of Additives That Spontaneously Form Cathode Interlayers in
      OPVs.
AB  - Interlayers between the active layer and the electrodes in organic devices are
      known to modify the electrode work function and enhance carrier
      extraction/injection, consequently improving device performance. It was recently
      demonstrated that chemical interactions between the evaporated electrode and
      interlayer additive can induce additive migration toward the metal/organic
      interface to spontaneously form the interlayer. In this work we used P3HT:PEG
      blends as a research platform to investigate the driving force for additive
      migration to the organic/metal interface and the source of the work function
      modification in OPVs. For this purpose PEG derivatives with different end groups
      were blended with P3HT or deposited on top of P3HT layer, topped with Al or Au
      evaporated electrodes. The correlation between the additive chemical structure,
      the Voc of corresponding devices, and the metal/organic interface composition
      determined by XPS revealed that the driving force for additive migration toward
      the blend/metal interface is the chemical interaction between the additives' end
      group and the deposited metal atoms. Replacing the PEG additives with alkyl
      additives bearing the same end groups has shown that the Al work function is
      actually modulated by the PEG backbone. Hence, in this work we have identified
      and separated between structural features controlling the migration of the
      interlayer additive to the organic/metal interface and those responsible for the
      modification of the metal work function. 

PMID- 25996273
TI  - Assessing the Effect of Personalized Diabetes Risk Assessments During
      Ophthalmologic Visits on Glycemic Control: A Randomized Clinical Trial.
AB  - IMPORTANCE: Optimization of glycemic control is critical to reduce the number of
      diabetes mellitus-related complications, but long-term success is challenging.
      Although vision loss is among the greatest fears of individuals with diabetes,
      comprehensive personalized diabetes education and risk assessments are not
      consistently used in ophthalmologic settings. OBJECTIVE: To determine whether the
      point-of-care measurement of hemoglobin A(1c) (HbA(1c)) and personalized diabetes
      risk assessments performed during retinal ophthalmologic visits improve glycemic
      control as assessed by HbA(1c) level. DESIGN, SETTING, AND PARTICIPANTS:
      Ophthalmologist office-based randomized, multicenter clinical trial in which
      investigators from 42 sites were randomly assigned to provide either a study
      prescribed augmented diabetes assessment and education or the usual care. Adults
      with type 1 or 2 diabetes enrolled into 2 cohorts: those with a more-frequent
      than-annual follow-up (502 control participants and 488 intervention
      participants) and those with an annual follow-up (368 control participants and
      388 intervention participants). Enrollment was from April 2011 through January
      2013. INTERVENTIONS: Point-of-care measurements of HbA1c, blood pressure, and
      retinopathy severity; an individualized estimate of the risk of retinopathy
      progression derived from the findings from ophthalmologic visits; structured
      comparison and review of past and current clinical findings; and structured
      education with immediate assessment and feedback regarding participant's
      understanding. These interventions were performed at enrollment and at routine
      ophthalmic follow-up visits scheduled at least 12 weeks apart. MAIN OUTCOMES AND
      MEASURES: Mean change in HbA(1c) level from baseline to 1-year follow-up.
      Secondary outcomes included body mass index, blood pressure, and responses to
      diabetes self-management practices and attitudes surveys. RESULTS: In the cohort
      with more-frequent-than-annual follow-ups, the mean (SD) change in HbA(1c) level
      at 1 year was -0.1% (1.5%) in the control group and -0.3% (1.4%) in the
      intervention group (adjusted mean difference, -0.09% [95% CI, -0.29% to 0.12%]; P
      = .35). In the cohort with annual follow-ups, the mean (SD) change in HbA(1c)
      level was 0.0% (1.1%) in the control group and -0.1% (1.6%) in the intervention
      group (mean difference, -0.05% [95% CI, -0.27% to 0.18%]; P = .63). Results were
      similar for all secondary outcomes. CONCLUSIONS AND RELEVANCE: Long-term
      optimization of glycemic control is not achieved by a majority of individuals
      with diabetes. The addition of personalized education and risk assessment during
      retinal ophthalmologic visits did not result in a reduction in HbA(1c) level
      compared with usual care over 1 year. These data suggest that optimizing glycemic
      control remains a substantive challenge requiring interventional paradigms other
      than those examined in our study. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier:NCT01323348.

PMID- 25996287
TI  - Intimate partner violence and forced migration during pregnancy: Structural
      constraints to women's agency.
AB  - Little is known about migration during pregnancy related to intimate partner
      violence (IPV). In this paper, we examine issues of agency in relation to
      pregnant women's migrations in a high HIV prevalence area of Kenya. We
      qualitatively explored forced migration among pregnant women, using data from in
      depth interviews, focus groups and IPV screening forms. To quantitatively examine
      migration during pregnancy, we analysed data from a prospective study of 614
      pregnant women. The qualitative data revealed that women had varied responses to
      violence in pregnancy, with some being able to leave the marital home voluntarily
      as a strategy to escape violence. Others were 'sent packing' from their marital
      homes when they dared to exercise autonomy, in some cases related to HIV status.
      Quantitative analyses revealed that pregnant women who migrated were more
      educated, less likely to be living with a partner and had fewer children than
      other women. Migration among pregnant women in Kenya illustrates the complexity
      of understanding women's agency in the context of IPV. The findings indicate that
      there is not a dichotomy between 'victim' and 'agent', but rather a complex
      dynamic between and within pregnant women, who may sequentially or simultaneously
      experience aspects of victimhood and/or agentic response. 

PMID- 25996288
TI  - Effect of Delayed Bonding and Antioxidant Application on the Bond Strength to
      Enamel after Internal Bleaching.
AB  - PURPOSE: This study evaluated the effect of delayed bonding and antioxidant
      application (AA, 10% sodium ascorbate) after internal bleaching (35% carbamide
      peroxide) on the shear bond strength of an adhesive cement to enamel. MATERIALS
      AND METHODS: Eighty-four human maxillary central incisors were endodontically
      treated. The control group remained unbleached with no AA. Experimental groups
      were all internally bleached. The buccal enamel was finished and polished with
      metallographic paper to a refinement of #600, in order to obtain a 5-mm(2) flat
      bonding area. An adhesive cement (Clearfil Esthetic) was placed into a plastic
      tube with internal diameter of 3 mm and a 3-mm height and cured on the enamel.
      Bonding occurred either immediately after bleaching (group Im), a 7-day delay
      (group 7), or a 14-day delay (group 14), and half the specimens were treated with
      antioxidant application (groups Im-AA, 7-AA, and 14-AA). Shear bond strength
      testing was performed on a universal testing machine, and data were analyzed with
      ANOVA and Fisher test (5%). RESULTS: Delaying of bonding is a useful factor for
      enhancing shear bond strength (p < 0.05), whereas AA only enhanced shear bond
      strength after 7 days delayed bleaching (p < 0.05). The highest bond strength was
      noted in groups 7-AA (20.51 +/- 4.5 MPa), 14 (19.82 +/- 4.6), 14-AA (20.27 +/-
      4.4), and control (20.51 +/- 5.1), which were not significantly different from
      each other. CONCLUSIONS: After internal bleaching, adhesive cementation to enamel
      is recommended only when delayed 14 days, or delayed 7 days with sodium ascorbate
      application.

PMID- 25996289
TI  - Efficacy and tolerability studies evaluating a sleep aid and analgesic
      combination of naproxen sodium and diphenhydramine in the dental impaction pain
      model in subjects with induced transient insomnia.
AB  - STUDY OBJECTIVES: The aim of this study was to evaluate the efficacy and
      tolerability of novel combination naproxen sodium (NS) and diphenhydramine (DPH)
      in subjects with postoperative dental pain along with transient insomnia induced
      by 5 h sleep phase advance. The present studies aimed to demonstrate the added
      benefit and optimal dosages of the combination product over individual
      ingredients alone in improving sleep and pain. METHODS: Each of the two studies
      was a two-centre, randomised, double-blind and double-dummy trial. In the first
      study, subjects were randomised into one of the following treatment arms: NS 440
      mg/DPH 50 mg, NS 220 mg/DPH 50 mg, NS 440 mg or DPH 50 mg. In the second study,
      subjects received either NS 440 mg/DPH 25 mg, NS 440 mg or DPH 50 mg. The co
      primary end-points in both studies were wake time after sleep onset (WASO) and
      sleep latency (SL) measured by actigraphy. Other secondary sleep and pain end
      points were also assessed. RESULTS: The intent-to-treat population included 712
      and 267 subjects from studies one and two, respectively. In the first study, only
      the NS 440 mg/DPH 50 mg combination showed significant improvements in both WASO
      vs. NS alone (-70.3 min p = 0.0002) and SL vs. DPH alone (25.50 and 41.50 min
      respectively, p < 0.0001). In the second study, the NS 440 mg/DPH 25 mg
      combination failed to show any significant improvements vs. either component
      alone. CONCLUSIONS: Only the NS 440 mg/DPH 50 mg combination demonstrated
      improvement in both sleep latency vs. DPH 50 mg and sleep maintenance (WASO) vs.
      NS 440 mg. There were no serious or unexpected adverse events reported in either
      study. CLINICAL TRIAL REGISTRATION: NCT01280591 (study 1); NCT01495858 (study 2).

PMID- 25996290
TI  - Systems-based approach to investigate unsafe pedestrian behaviour at level
      crossings.
AB  - Crashes at level crossings are a major issue worldwide. In Australia, as well as
      in other countries, the number of crashes with vehicles has declined in the past
      years, while the number of crashes involving pedestrians seems to have remained
      unchanged. A systematic review of research related to pedestrian behaviour
      highlighted a number of important scientific gaps in current knowledge. The
      complexity of such intersections imposes particular constraints to the
      understanding of pedestrians' crossing behaviour. A new systems-based framework,
      called Pedestrian Unsafe Level Crossing framework (PULC) was developed. The PULC
      organises contributing factors to crossing behaviour on different system levels
      as per the hierarchical classification of Jens Rasmussen's Framework for Risk
      Management. In addition, the framework adapts James Reason's classification to
      distinguish between different types of unsafe behaviour. The framework was
      developed as a tool for collection of generalizable data that could be used to
      predict current or future system failures or to identify aspects of the system
      that require further safety improvement. To give it an initial support, the PULC
      was applied to the analysis of qualitative data from focus groups discussions. A
      total number of 12 pedestrians who regularly crossed the same level crossing were
      asked about their daily experience and their observations of others' behaviour
      which allowed the extraction and classification of factors associated with errors
      and violations. Two case studies using Rasmussen's AcciMap technique are
      presented as an example of potential application of the framework. A discussion
      on the identified multiple risk contributing factors and their interactions is
      provided, in light of the benefits of applying a systems approach to the
      understanding of the origins of individual's behaviour. Potential actions towards
      safety improvement are discussed. 

PMID- 25996291
TI  - Che-1 modulates the decision between cell cycle arrest and apoptosis by its
      binding to p53.
AB  - The tumor suppressor p53 is mainly involved in the transcriptional regulation of
      a large number of growth-arrest- and apoptosis-related genes. However, a clear
      understanding of which factor/s influences the choice between these two opposing
      p53-dependent outcomes remains largely elusive. We have previously described that
      in response to DNA damage, the RNA polymerase II-binding protein Che-1/AATF
      transcriptionally activates p53. Here, we show that Che-1 binds directly to p53.
      This interaction essentially occurs in the first hours of DNA damage, whereas it
      is lost when cells undergo apoptosis in response to posttranscriptional
      modifications. Moreover, Che-1 sits in a ternary complex with p53 and the
      oncosuppressor Brca1. Accordingly, our analysis of genome-wide chromatin
      occupancy by p53 revealed that p53/Che1 interaction results in preferential
      transactivation of growth arrest p53 target genes over its pro-apoptotic target
      genes. Notably, exposure of Che-1(+/-) mice to ionizing radiations resulted in
      enhanced apoptosis of thymocytes, compared with WT mice. These results confirm
      Che-1 as an important regulator of p53 activity and suggest Che-1 to be a
      promising yet attractive drug target for cancer therapy. 

PMID- 25996292
TI  - Activation of NRG1-ERBB4 signaling potentiates mesenchymal stem cell-mediated
      myocardial repairs following myocardial infarction.
AB  - Mesenchymal stem cell (MSC) transplantation has achieved only modest success in
      the treatment of ischemic heart disease owing to poor cell viability in the
      diseased microenvironment. Activation of the NRG1 (neuregulin1)-ERBB4 (v-erb-b2
      avian erythroblastic leukemia viral oncogene homolog 4) signaling pathway has
      been shown to stimulate mature cardiomyocyte cell cycle re-entry and cell
      division. In this connection, we aimed to determine whether overexpression of
      ERBB4 in MSCs can enhance their cardio-protective effects following myocardial
      infarction. NRG1, MSCs or MSC-ERBB4 (MSC with ERBB4 overexpression), were
      transplanted into mice following myocardial infarction. Superior to that of MSCs
      and solely NRG1, MSC-ERBB4 transplantation significantly preserved heart
      functions accompanied with reduced infarct size, enhanced cardiomyocyte division
      and less apoptosis during early phase of infarction. The transduction of ERBB4
      into MSCs indeed increased cell mobility and apoptotic resistance under hypoxic
      and glucose-deprived conditions via a PI3K/Akt signaling pathway in the presence
      of NRG1. Unexpectedly, introduction of ERBB4 into MSC in turn potentiates NRG1
      synthesis and secretion, thus forming a novel NRG1-ERBB4-NRG1 autocrine loop.
      Conditioned medium of MSC-ERBB4 containing elevated NRG1, promoted cardiomyocyte
      growth and division, whereas neutralization of NRG1 blunted this proliferation.
      These findings collectively suggest that ERBB4 overexpression potentiates MSC
      survival in the infarcted heart, enhances NRG1 generation to restore declining
      NRG1 in the infarcted region and stimulates cardiomyocyte division. ERBB4 has an
      important role in MSC-mediated myocardial repairs. 

PMID- 25996293
TI  - miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting
      ATG12 and HMGB2.
AB  - Chemotherapy is an important treatment modality for gastric cancer (GC); however,
      it usually fails because of drug resistance, especially multidrug resistance
      (MDR). Previously, we found a novel subset of MDR-associated microRNAs (miRNAs)
      through high-throughput functional screening. In this report, we investigated the
      exact roles and mechanisms of miR-23b-3p in the MDR of GC. Using gain or loss-of
      function in in vitro and in vivo experiments, we found that overexpression of miR
      23b-3p reversed cancer cell resistance to multiple chemotherapeutics in vitro and
      sensitize tumors to chemotherapy in vivo. Reporter gene assay and western blot
      analysis showed that ATG12 and HMGB2 were the direct targets of miR-23b-3p.
      Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of
      autophagy. Reducing the expression of these target genes by siRNA or inhibition
      of autophagy both sensitized GC cells to chemotherapy. These findings suggest
      that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in
      MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for
      overall survival in GC. In conclusion, our data demonstrated that miR-23b-3p
      inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to
      chemotherapy, and suggested the potential application of miR-23b-3p in drug
      resistance prediction and treatment. 

PMID- 25996294
TI  - A cellular screen identifies ponatinib and pazopanib as inhibitors of
      necroptosis.
AB  - Necroptosis is a form of regulated necrotic cell death mediated by receptor
      interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3. Necroptotic cell
      death contributes to the pathophysiology of several disorders involving tissue
      damage, including myocardial infarction, stroke and ischemia-reperfusion injury.
      However, no inhibitors of necroptosis are currently in clinical use. Here we
      performed a phenotypic screen for small-molecule inhibitors of tumor necrosis
      factor-alpha (TNF-alpha)-induced necroptosis in Fas-associated protein with death
      domain (FADD)-deficient Jurkat cells using a representative panel of Food and
      Drug Administration (FDA)-approved drugs. We identified two anti-cancer agents,
      ponatinib and pazopanib, as submicromolar inhibitors of necroptosis. Both
      compounds inhibited necroptotic cell death induced by various cell death receptor
      ligands in human cells, while not protecting from apoptosis. Ponatinib and
      pazopanib abrogated phosphorylation of mixed lineage kinase domain-like protein
      (MLKL) upon TNF-alpha-induced necroptosis, indicating that both agents target a
      component upstream of MLKL. An unbiased chemical proteomic approach determined
      the cellular target spectrum of ponatinib, revealing key members of the
      necroptosis signaling pathway. We validated RIPK1, RIPK3 and transforming growth
      factor-beta-activated kinase 1 (TAK1) as novel, direct targets of ponatinib by
      using competitive binding, cellular thermal shift and recombinant kinase assays.
      Ponatinib inhibited both RIPK1 and RIPK3, while pazopanib preferentially targeted
      RIPK1. The identification of the FDA-approved drugs ponatinib and pazopanib as
      cellular inhibitors of necroptosis highlights them as potentially interesting for
      the treatment of pathologies caused or aggravated by necroptotic cell death. 

PMID- 25996295
TI  - The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via
      attenuation of host ubiquitin ligase RNF43.
AB  - The interplay between influenza virus and host factors to support the viral life
      cycle is well documented. Influenza A virus (IAV) proteins interact with an array
      of cellular proteins and hijack host pathways which are at the helm of cellular
      responses to facilitate virus invasion. The multifaceted nature of the
      ubiquitination pathway for protein regulation makes it a vulnerable target of
      many viruses including IAV. To this end we conducted a yeast two-hybrid screen to
      search for cellular ubiquitin ligases important for influenza virus replication.
      We identified host protein, RING finger protein 43 (RNF43), a RING-type E3
      ubiquitin ligase, as a novel interactor of nucleoprotein (NP) of IAV and an
      essential partner to induce NP-driven p53-mediated apoptosis in IAV-infected
      cells. In this study, we demonstrate that IAV leads to attenuation of RNF43
      transcripts and hence its respective protein levels in the cellular milieu
      whereas in RNF43 depleted cells, viral replication was escalated several folds.
      Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization
      resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto
      unknown process targeted by NP for p53 stabilization and accumulation.
      Collectively, these results conclude that NP targets RNF43 to modulate p53
      ubiquitination levels and hence causes p53 stabilization which is conducive to an
      enhanced apoptosis level in the host cells. In conclusion, our study unravels a
      novel strategy adopted by IAV for utilizing the much conserved ubiquitin
      proteasomal pathway. 

PMID- 25996296
TI  - Necrosis- and apoptosis-related Met cleavages have divergent functional
      consequences.
AB  - Upon activation by its ligand hepatocyte growth factor/scatter factor, the
      receptor tyrosine kinase Met promotes survival, proliferation, and migration of
      epithelial cells during embryogenesis. Deregulated Met signaling can also promote
      cancer progression and metastasis. Met belongs to the functional family of
      dependence receptors whose activity switches from pro-survival to pro-apoptotic
      during apoptosis upon caspase cleavage. Although apoptosis resistance is a
      hallmark of cancer cells, some remain sensitive to other cell death processes,
      including necrosis induced by calcium stress. The role and fate of Met during
      necrotic cell death are unknown. Following treatment with calcium ionophores,
      cell lines and primary cells undergo necrosis, and the full-length Met receptor
      is efficiently degraded. This degradation is achieved by double cleavage of Met
      in its extracellular domain by a metalloprotease of the A disintegrin and
      metalloproteinase (ADAM) family and in its intracellular domain by calpains
      (calcium-dependent proteases). These cleavages separate the Met extracellular
      region from its kinase domain, thus preventing Met activity and its potential pro
      survival activity. Although the intracellular fragment is very similar to the
      fragment generated by caspases, it displays no pro-apoptotic property, likely
      because of the presence of the last few amino acids of Met, known to inhibit this
      pro-apoptotic function. The fragments identified here are observed in lung tumors
      overexpressing the Met receptor, along with fragments previously identified,
      suggesting that proteolytic cleavages of Met are involved in its degradation in
      tumor tissues. Thus, Met is a modulator of necrosis, able to protect cells when
      activated by its ligand but efficiently degraded by proteolysis when this process
      is engaged. 

PMID- 25996297
TI  - Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing
      lysosomal acidification, which is unfavorable for HBV replication.
AB  - Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, exhibits
      diverse beneficial properties, including antiviral activity. Autophagy is a
      cellular process that is involved in the degradation of long-lived proteins and
      damaged organelles. Recent evidence indicates that modulation of autophagy is a
      potential therapeutic strategy for various viral diseases. In the present study,
      we investigated the effect of EGCG on hepatitis B virus (HBV) replication and the
      possible involvement of autophagy in this process. Our results showed that HBV
      induced autophagosome formation, which was required for replication of itself.
      However, although EGCG efficiently inhibited HBV replication, it enhanced, but
      not inhibited, autophagosome formation in hepatoma cells. Further study showed
      that HBV induced an incomplete autophagy, while EGCG, similar to starvation, was
      able to induce a complete autophagic process, which appeared to be unfavorable
      for HBV replication. Furthermore, it was found that HBV induced an incomplete
      autophagy by impairing lysosomal acidification, while it lost this ability in the
      presence of EGCG. Taken together, these data demonstrated that EGCG treatment
      opposed HBV-induced incomplete autophagy via enhancing lysosomal acidification,
      which was unfavorable for HBV replication. 

PMID- 25996299
TI  - Optic Perineuritis in Behcet Disease.
AB  - BACKGROUND: Optic perineuritis (OPN), an uncommon optic neuropathy, has
      previously not been described in patients with Behcet disease (BD). We conducted
      this study to describe the clinical features, response to treatment, and outcome
      of OPN due to BD, with particular emphasis on those features that might
      distinguish this from the idiopathic variety. METHODS: This is a retrospective,
      case series review of all patients with a diagnosis of OPN seen in a hospital
      based neurology department from 2008 to 2014 who also met the international
      criteria for the diagnosis of BD. RESULTS: Twenty-one patients with OPN were
      identified, of whom 10 (12 eyes) met the criteria for BD. OPN developed 2-10
      years (mean, 4 years) after onset of BD, but the diagnosis of BD was made only
      after onset of OPN in 6. Nine of 12 eyes (75%) had severe visual loss (<=20/200),
      and 80% of patients progressed over several days from onset. After high-dose
      corticosteroid treatment, all patients experienced relief of pain, and 5 patients
      (50%) showed improved visual acuity. At last follow-up (mean, 25 months) 7 of 11
      (64%) of affected eyes had good visual outcome (>=14/20), and no patient
      experienced a subsequent neurological event. CONCLUSIONS: OPN may occur as a
      manifestation of BD and, in non-Western countries, this may be more common than
      the idiopathic variety. In contrast to idiopathic cases, OPN in BD is more likely
      to demonstrate initial rapid progression of visual loss and more severe loss at
      presentation. Patients show less recovery of vision in response to
      corticosteroids but carry a lower rate of subsequent relapse. Patients with OPN
      should be specifically questioned regarding symptoms of BD.

PMID- 25996298
TI  - Electric Blanket Use and Risk of Thyroid Cancer in the Women's Health Initiative
      Observational Cohort.
AB  - Thyroid cancer disproportionally affects more women than men. The aim of this
      study was to assess whether exposure to extremely low frequency electric magnetic
      fields from electric blankets (EBs) was associated with the development of
      thyroid cancer. Data were analyzed from 89,527 women who participated in the
      Women's Health Initiative Observational Study and who responded to questions
      concerning prior use of EBs. During a mean follow-up of 12.2 years, 190 incident
      cases of thyroid cancer were identified. We estimated the hazard ratio (HR) and
      95 percent confidence interval (CI) of incident thyroid cancer associated with EB
      use by Cox's proportional hazard model, adjusted for selected covariates. A
      majority, 57 percent, of the women in the cohort reported the use of EBs while
      sleeping and/or for warming the bed before sleep. No association was found
      between use of EBs and subsequent risk of thyroid cancer (HR = 0.98, 95 percent
      CI 0.72-1.32). Duration of EB use measured in years, months, or hours had no
      effect on risk. These results did not change when the cases were limited to
      papillary thyroid cancer, the most frequently occurring histologic type. The
      results of this study do not support possible health hazards of EBs in regards to
      thyroid cancer risk. 

PMID- 25996301
TI  - Waldenstrom Macroglobulinemia Mimicking Temporal Arteritis.

PMID- 25996300
TI  - Physiological Correlates and Predictors of Functional Recovery After Chiasmal
      Decompression.
AB  - BACKGROUND: The intrinsic abilities and limits of the nervous system to repair
      itself after damage may be assessed using a model of optic chiasmal compression,
      before and after a corrective surgical procedure. METHODS: Visual fields (VFs),
      multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL)
      thickness, and diffusion tensor imaging were used to evaluate a patient before
      and after removal of a meningioma compressing the chiasm. Normally sighted
      individuals served as controls. The advantage of each modality to document visual
      function and predict postoperative outcome (2-year follow-up) was evaluated.
      RESULTS: Postsurgery visual recovery was best explained by critical mass of
      normally conducting fibers and not associated with average conduction amplitudes.
      Recovered VF was observed in quadrants in which more than 50% of fibers were
      identified, characterized by intact mfVEP latencies, but severely reduced
      amplitudes. Recovery was evident despite additional reduction of RNFL thickness
      and abnormal optic tract diffusivity. The critical mass of normally conducting
      fibers was also the best prognostic indicator for functional outcome 2 years
      later. CONCLUSIONS: Our results highlight the ability of the remaining normally
      conductive axons to predict visual recovery after decompression of the optic
      chiasm. The redundancy in anterior visual pathways may be explained,
      neuroanatomically, by overlapping receptive fields.

PMID- 25996302
TI  - Isolated Horner Syndrome From an Elongated Styloid Process (Eagle Syndrome).
AB  - Eagle syndrome occurs when an elongated styloid process causes otolaryngological
      or neurological symptoms or signs. We report a patient who had an isolated
      asymptomatic Horner syndrome that resulted from a pinned internal carotid artery
      being dynamically injured by an elongated styloid process during chiropractic
      neck manipulation. There was no evidence of arterial dissection. 

PMID- 25996303
TI  - Heterosides--compatible solutes occurring in prokaryotic and eukaryotic
      phototrophs.
AB  - The acclimation to osmotic and/or salt stress conditions induces an integrated
      response at different cellular levels. One acclimation strategy relies on the
      massive accumulation of low molecular mass compounds, so-called compatible
      solutes, to balance osmotic gradients and to directly protect critical
      macromolecules. Heterosides are compounds composed of a sugar and a polyol moiety
      that represent one chemical class of compatible solutes with interesting
      features. Well-investigated examples are glucosylglycerol, which is found in many
      cyanobacteria, and galactosylglycerols (floridoside and isofloridoside), which
      are accumulated by eukaryotic algae under salt stress conditions. Here, we review
      knowledge on physiology, biochemistry and genetics of heteroside accumulation in
      pro- and eukaryotic photoautotrophic organisms. 

PMID- 25996305
TI  - All regulators great and small: when Treg need small RNAs to fulfill their
      commitment.

PMID- 25996306
TI  - Bridge- and solvent-mediated intramolecular electronic communications in
      ubiquinone-based biomolecular wires.
AB  - Intramolecular electronic communications of molecular wires play a crucial role
      for developing molecular devices. In the present work, we describe different
      degrees of intramolecular electronic communications in the redox processes of
      three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by
      electrochemistry and Density Functional Theory (DFT) methods in different
      solvents. We found that the bridges linkers have a significant effect on the
      electronic communications between the two peripheral ubiquinone moieties and
      solvents effects are limited and mostly depend on the nature of solvents. The DFT
      calculations for the first time indicate the intensity of the electronic
      communications during the redox processes rely on the molecular orbital elements
      VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1),
      which is could be affected by the bridges linkers. The DFT calculations also
      demonstrates the effect of solvents on the latter two-electron transfer of Bis
      CoQ0s is more significant than the former two electrons transfer as the observed
      electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry
      and theoretical calculations reveal the intramolecular electronic communications
      vary in the four-electron redox processes of three Bis-CoQ0s. 

PMID- 25996308
TI  - Clean WS2 and MoS2 Nanoribbons Generated by Laser-Induced Unzipping of the
      Nanotubes.
AB  - The preparation of 1D WS(2) and MoS(2) flexible nanoribbons by laser-induced
      unzipping of the nanotubes is reported. The nanoribbons are of high quality,
      uniform width, and devoid of surface contamination. The zig-zag edges in WS(2)
      nanoribbons give rise to ferromagnetism at room temperature.

PMID- 25996307
TI  - Sandwiched confinement of quantum dots in graphene matrix for efficient electron
      transfer and photocurrent production.
AB  - Quantum dots (QDs) and graphene are both promising materials for the development
      of new-generation optoelectronic devices. Towards this end, synergic assembly of
      these two building blocks is a key step but remains a challenge. Here, we show a
      one-step strategy for organizing QDs in a graphene matrix via interfacial self
      assembly, leading to the formation of sandwiched hybrid QD-graphene nanofilms. We
      have explored structural features, electron transfer kinetics and photocurrent
      generation capacity of such hybrid nanofilms using a wide variety of advanced
      techniques. Graphene nanosheets interlink QDs and significantly improve
      electronic coupling, resulting in fast electron transfer from photoexcited QDs to
      graphene with a rate constant of 1.3 * 10(9) s(-1). Efficient electron transfer
      dramatically enhances photocurrent generation in a liquid-junction QD-sensitized
      solar cell where the hybrid nanofilm acts as a photoanode. We thereby demonstrate
      a cost-effective method to construct large-area QD-graphene hybrid nanofilms with
      straightforward scale-up potential for optoelectronic applications.

PMID- 25996309
TI  - Parallel Synthesis of Hexahydrodiimidazodiazepines Heterocyclic Peptidomimetics
      and Their in Vitro and in Vivo Activities at MU (MOR), delta (DOR), and kappa
      (KOR) Opioid Receptors.
AB  - In the development of analgesics with mixed-opioid agonist activity, peripherally
      selective activity is expected to decrease side effects, minimizing respiratory
      depression and reinforcing properties generating significantly safer analgesic
      therapeutics. We synthesized diazaheterocyclics from reduced tripeptides. In
      vitro screening with radioligand competition binding assays demonstrated variable
      affinity for MU (MOR), delta (DOR), and kappa (KOR) opioid receptors across the
      series, with the diimidazodiazepine 14 (2065-14) displaying good affinity for DOR
      and KOR. Central (icv), intraperitoneal (ip), or oral (po) administration of 14
      produced dose-dependent, opioid-receptor mediated antinociception in the mouse,
      as determined from a 55  degrees C warm-water tail-withdrawal assay. Only trace
      amounts of compound 14 was found in brain up to 90 min later, suggesting poor BBB
      penetration and possible peripherally restricted activity. Central administration
      of 14 did not produce locomotor effects, acute antinociceptive tolerance, or
      conditioned-place preference or aversion. The data suggest these
      diazaheterocyclic mixed activity opioid receptor agonists may hold potential as
      new analgesics with fewer liabilities of use. 

PMID- 25996310
TI  - Synthesis and evaluation of new dithiocarbamic acid 6,11-dioxo-6,11-dihydro-1H
      anthra[1,2-d]-imidazol-2-yl methyl esters.
AB  - A novel series of dithiocarbamic acid 6,11-dioxo-6,11-dihydro-1H-anthra[1,2
      d]imidazol-2-yl methyl esters were synthesized and their cytotoxic and apoptotic
      activities were evaluated on HeLa cells. Some of these compounds showed potent
      cytotoxic activities and are able to induce the apoptosis mechanism in this cell
      line. Especially, 2c, 2d, and 2f had a high cytotoxic activity with an IC50 value
      of 8 or 10 MUM at 24 h. These three compounds also induced HeLa cell apoptosis as
      compared to mitoxantrone. Particularly, 3 MUM of 2f induced a high rate of early
      apoptotic cells (12.9%) at 6 h whereas mitoxantrone induced early apoptosis
      (5.5%) at 24 h. Compound 2c demonstrated a high ADP/ATP ratio (9.31) in HeLa
      cells at 12 h compared to mitoxantrone or other compounds, suggesting that 2c
      might induce HeLa cell apoptosis through the mitochondrial pathway. Caspase-3
      activity started to increase after treatment with 6 MUM of 2c for 6 h, and the
      maximal peak of activity was obtained at 12 h of incubation time. All three
      compounds were found to be potent apoptotic inducers compared to mitoxantrone. 

PMID- 25996311
TI  - Monolayer PtSe2, a New Semiconducting Transition-Metal-Dichalcogenide,
      Epitaxially Grown by Direct Selenization of Pt.
AB  - Single-layer transition-metal dichalcogenides (TMDs) receive significant
      attention due to their intriguing physical properties for both fundamental
      research and potential applications in electronics, optoelectronics, spintronics,
      catalysis, and so on. Here, we demonstrate the epitaxial growth of high-quality
      single-crystal, monolayer platinum diselenide (PtSe2), a new member of the
      layered TMDs family, by a single step of direct selenization of a Pt(111)
      substrate. A combination of atomic-resolution experimental characterizations and
      first-principle theoretic calculations reveals the atomic structure of the
      monolayer PtSe2/Pt(111). Angle-resolved photoemission spectroscopy measurements
      confirm for the first time the semiconducting electronic structure of monolayer
      PtSe2 (in contrast to its semimetallic bulk counterpart). The photocatalytic
      activity of monolayer PtSe2 film is evaluated by a methylene-blue
      photodegradation experiment, demonstrating its practical application as a
      promising photocatalyst. Moreover, circular polarization calculations predict
      that monolayer PtSe2 has also potential applications in valleytronics. 

PMID- 25996312
TI  - A gold@polydopamine core-shell nanoprobe for long-term intracellular detection of
      microRNAs in differentiating stem cells.
AB  - The capability of monitoring the differentiation process in living stem cells is
      crucial to the understanding of stem cell biology and the practical application
      of stem-cell-based therapies, yet conventional methods for the analysis of
      biomarkers related to differentiation require a large number of cells as well as
      cell lysis. Such requirements lead to the unavoidable loss of cell sources and
      preclude real-time monitoring of cellular events. In this work, we report the
      detection of microRNAs (miRNAs) in living human mesenchymal stem cells (hMSCs) by
      using polydopamine-coated gold nanoparticles (Au@PDA NPs). The PDA shell
      facilitates the immobilization of fluorescently labeled hairpin DNA strands
      (hpDNAs) that can recognize specific miRNA targets. The gold core and PDA shell
      quench the fluorescence of the immobilized hpDNAs, and subsequent binding of the
      hpDNAs to the target miRNAs leads to their dissociation from Au@PDA NPs and the
      recovery of fluorescence signals. Remarkably, these Au@PDA-hpDNA nanoprobes can
      naturally enter stem cells, which are known for their poor transfection
      efficiency, without the aid of transfection agents. Upon cellular uptake of these
      nanoprobes, we observe intense and time-dependent fluorescence responses from two
      important osteogenic marker miRNAs, namely, miR-29b and miR-31, only in hMSCs
      undergoing osteogenic differentiation and living primary osteoblasts but not in
      undifferentiated hMSCs and 3T3 fibroblasts. Strikingly, our nanoprobes can afford
      long-term tracking of miRNAs (5 days) in the differentiating hMSCs without the
      need of continuously replenishing cell culture medium with fresh nanoprobes. Our
      results demonstrate the capability of our Au@PDA-hpDNA nanoprobes for monitoring
      the differentiation status of hMSCs (i.e., differentiating versus
      undifferentiated) via the detection of specific miRNAs in living stem cells. Our
      nanoprobes show great promise in the investigation of the long-term dynamics of
      stem cell differentiation, identification and isolation of specific cell types,
      and high-throughput drug screening. 

PMID- 25996314
TI  - Synthesis, structure, and luminescence properties of SrSiAl2O3N2:Eu(2+) phosphors
      for light-emitting devices and field emission displays.
AB  - A series of SrSiAl2O3N2:Eu(2+) (0.005 <=x<= 0.05) phosphors were successfully
      synthesized through a pressureless, facile, and efficient solid state route. The
      crystal structure, band structure, and their photoluminescence and
      cathodoluminescence properties were investigated in detail. The phosphors exhibit
      rod shape morphology with a uniform Eu(2+) distribution. Under n-UV excitation
      the emission spectra shift from 477 to 497 nm with an increase of Eu(2+)
      concentration. The concentration quenching mechanism of Eu(2+) emission was
      dominated by the dipole-dipole interaction. The thermal stability is comparable
      to that of the commercial Ba2SiO4:Eu(2+) phosphor. The phosphor also exhibits
      high current saturation and high resistance under low voltage electron
      bombardment. All the results indicate that the SrSiAl2O3N2:Eu(2+) phosphors can
      be considered as candidates for application in both white LEDs and FEDs. 

PMID- 25996315
TI  - Diagnostic errors in medical practice.

PMID- 25996316
TI  - Neonatal mortality risk prediction.

PMID- 25996313
TI  - Mass spectrometry tools and workflows for revealing microbial chemistry.
AB  - Since the time Van Leeuwenhoek was able to observe microbes through a microscope,
      an innovation that led to the birth of the field of microbiology, we have aimed
      to understand how microorganisms function, interact and communicate. The exciting
      progress in the development of analytical technologies and workflows has
      demonstrated that mass spectrometry is a very powerful technique for the
      interrogation of microbiology at the molecular level. In this review, we aim to
      highlight the available and emerging tools in mass spectrometry for microbial
      analysis by overviewing the methods and workflow advances for taxonomic
      identification, microbial interaction, dereplication and drug discovery. We
      emphasize their potential for future development and point out unsolved problems
      and future directions that would aid in the analysis of the chemistry produced by
      microbes. 

PMID- 25996317
TI  - Cross-cultural adaptation of a questionnaire that evaluates physical activity
      among children aged 10 and 11.
AB  - OBJECTIVE: To adapt to certain cultural patterns and to localize into Spanish the
      Previous Day Physical Activity Recall questionnaire and to evaluate its content,
      acceptability and reliability. METHOD: The Previous Day Physical Activity Recall
      questionnaire was subjected to a process of direct translation, back translation
      and final pretesting. Judges assessed their semantic, idiomatic and conceptual
      equivalences. A preliminary version was pretested. Afterwards, a reliability
      analysis was made through a test-retesting. According to the committee of judges
      the rate of agreement was determined using the content validity index and the
      mean of the judges' scores. Acceptability, through the number of questionnaires
      with mismatching answers. Reliability was assessed by the stability criterion.
      RESULTS: The translated version of the questionnaire reached appropriate
      semantic, idiomatic and conceptual equivalences with a high content validity
      index in all the evaluated documents. The 32 schoolchildren that did the pretest
      employed a mean time of 18 minutes to complete it; 6 subjects replied, at least,
      1 mismatched answer; only one questionnaire was discarded (more than 4 mismatch
      answers). The test-retesting analysis, conducted with 73 school children, showed
      an intra class correlation coefficient of 0.99 regarding the total metabolic
      equivalents and of 0.98 and 0.97 for the moderate and vigorous physical activity
      blocks, respectively. CONCLUSIONS: The adaptation to certain cultural patterns
      and the localization into the Spanish language of the Previous Day Physical
      Activity Recall questionnaire showed successful results in each of the studied
      settings.

PMID- 25996318
TI  - Prevention of respiratory tract infections: Situation in 12 private day care
      centers in the city of Buenos Aires.
AB  - INTRODUCTION: Day care center attendance is a risk factor for acquiring
      respiratory tract infections. There are preventive measures which should be
      applied. OBJECTIVES: To describe the availability of adequate supplies or
      building facilities, staff habits, behaviors and training, and the existence and
      enforcement of official guidelines or institutional standards regarding the
      prevention of respiratory tract infections in day care centers for infants in the
      city of Buenos Aires. METHODS: Exploratory and cross sectional study carried out
      at systematically selected private day care centers for infants. The person
      responsible of the day care center was interviewed and a 3-hour observation
      session was held in a room of each of the day care centers. Information was
      collected on hand washing practices, clearance of nasal secretions, school
      exclusion guidance, immunization control, breastfeeding promotion and the
      existence of guidelines, standards and training on the prevention of respiratory
      tract infections. RESULTS: Twelve day care centers were included. Though 8 of the
      12 centers had the necessary infrastructure and items, hand washing was uncommon
      and the technique used was incorrect. Clearance of nasal secretions was not
      followed by hand washing. At 11 of the 12 day care centers, children's
      immunization is monitored; at 9 of 12, school exclusion guidelines are not
      followed; none of the centers have breastfeeding promotion material. In 1 of 12,
      teachers were trained in the subject the year before and, 1 out of 12 had its own
      guidelines for infection prevention. CONCLUSION: Despite the availability of
      resources, preventive measures were not regularly and systematically implemented
      in the day care centers visited.

PMID- 25996319
TI  - Development and validation of the Neonatal Mortality Score-9 Mexico to predict
      mortality in critically ill neonates.
AB  - INTRODUCTION: Prognostic scales or scores are useful for physicians who work in
      neonatal intensive care units. There are several validated neonatal scores but
      they are mostly applicable to low birth weight infants. The aim of this study was
      to develop and validate a mortality prognostic score in newborn infants, that
      would include new prognostic outcome measures. POPULATION AND METHODS: The study
      was conducted in a mother and child hospital in the city of Mexico, part of the
      Instituto Mexicano del Seguro Social (Mexican Institute of Social Security). In
      the first phase of the study, a nested case-control study was designed (newborn
      infants admitted on the basis of severity criteria during the first day of life),
      in which a scale was identified and developed with gradual parameters of
      cumulative score consisting of nine independent outcome measures to predict
      death, as follows: weight, metabolic acidemia, lactate, PaO2/FiO2, p(A-a) O2,
      A/a, platelets and serum glucose.Validation was performed in a matched
      prospective cohort, using 7-day mortality as an endpoint. RESULTS: The initial
      cohort consisted of 424 newborn infants. Twenty-two cases and 132 controls were
      selected; and 9 outcome measures were identified, making up the scale named
      neonatal mortality score-9 Mexico. The validation cohort consisted of 227 newborn
      infants. Forty-four (19%) deaths were recorded, with an area under the curve
      (AUC) of 0.92. With a score between 16 and 18, an 85 (11-102) hazard ratio, 99%
      specificity, 71% positive predictive value and 90% negative predictive value were
      reported. Conclusions .The proposed scale is a reliable tool to predict severity
      in newborn infants.

PMID- 25996320
TI  - Validation of the Pediatric Index of Mortality 2 (PIM2) in Argentina: a
      prospective, multicenter, observational study.
AB  - INTRODUCTION: The Pediatric Index of Mortality 2 (PIM2) is one of the most
      commonly used scoring systems to predict mortality in patients admitted to
      pediatric intensive care units (PICU) in Argentina. The objective of this study
      was to validate the PIM2 score in PICUs participating in the Quality of Care
      Program promoted by the Argentine Society of Intensive Care. POPULATION AND
      METHODS: Multicenter, prospective, observational, cross-sectional study. All
      patients between 1 month and 16 years old admitted to participating PICUs between
      January 1st, 2009 and December 31st, 2009 were included. The discrimination and
      calibration of the PIM2 score were assessed in the entire population and in
      different subgroups (risk of mortality, age, diagnoses on admission). RESULTS:
      Two thousand, eight hundred and thirty-two patients were included. PIM2 predicted
      246 deaths; however, 297 patients died (p < 0.01). The standardized mortality
      ratio was 1.20 (95% confidence interval [CI]: 1.01-1.43). The area under the ROC
      curve was 0.84 (95% CI: 0.82-0.86). Statistically significant differences were
      detected between the observed and the predicted mortality for the entire
      population and for the different risk intervals (chi2: 71.02, df: 8, p < 0.001).
      Statistically significant differences were also found between observed and
      predicted mortality in adolescent patients (37/22, p = 0.03) and in those
      hospitalized due to respiratory disease (105/81, p = 0.03). CONCLUSIONS: The PIM2
      score adequately discriminates survivors from non-survivors. However, it
      underscores the overall risk of death, especially in adolescent patients and
      those hospitalized due to respiratory disease. It is critical to take such
      differences into account when interpreting results.

PMID- 25996321
TI  - Evaluation of an improvement strategy on the incidence of medication prescribing
      errors in a pediatric intensive care unit.
AB  - Medical prescribing errors (MPEs) are one of the most common causes of adverse
      events. Intensive care units are a high-risk setting for their occurrence.
      OBJECTIVES: To describe the incidence and types of MPEs in our Pediatric
      Intensive Care Unit. To assess whether the implementation of an improvement
      strategy on MPEs affects their incidence in the short- and long-term. POPULATION
      AND METHODS: Prospective, uncontrolled, before-after study. Universe and sample.
      All medical prescriptions for patients hospitalized in the Pediatric Intensive
      Care Unit of the Hospital General de Ninos Pedro de Elizalde from July-December,
      2013 and from July-August, 2014. RESULTS: In the pre-intervention period, MPEs
      rate was 13.9%, the most common being the absence of the time a given medication
      was modified, followed by missing a dose or medication. The medication most
      frequently involved in MPEs was the sedation and continuous analgesia group.
      After the implementation of an improvement program on MPEs, the incidence
      decreased to 6.3 errors every 100 prescriptions. The MPE type which showed the
      greatest reduction was the absence of the time of modification. Except for
      parenteral hydration and electrolyte supplementation, the rest of the analyzed
      medication groups showed a marked reduction. One year after having reviewed the
      situation, the MPE rate was 5.8%, and values remained similar to those of the
      immediate postintervention period. CONCLUSION: Managing an improvement program on
      MPEs resulted in a decrease in its incidence.

PMID- 25996322
TI  - Varicella at "Casa Garrahan", 2008-2013: Assessment of postexposure prophylaxis
      measures.
AB  - INTRODUCTION: Casa Garrahan (CG) accommodates children with complex conditions
      referred nationwide; these children are seen in children's hospitals located in
      the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease,
      with attack rates of up to 90% among susceptible individuals. In closed
      communities, the implementation of outbreak control measures is critical.
      OBJECTIVES: To describe the characteristics of children exposed to varicella at
      CG, the implemented prophylaxis measures and their effectiveness. METHODS:
      Prospective, cohort study. Children exposed to varicella at CG between2008 and
      2013, their demographic and clinical characteristics, immunization and/or history
      of varicella, prophylaxis measures, and secondary attack rate were assessed.
      RESULTS: N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84
      months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had
      an underlying disease [hemato-oncological disease: 39% (n: 42); neurological
      disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative
      period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54).
      Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated
      that they never had the infection; and 41% (n: 44) did not recall a history of
      varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age
      and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65);
      immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects
      were observed in relation to the different prophylaxis measures. No secondary
      cases were observed at 30 days. CONCLUSIONS: Implemented measures were effective
      to prevent secondary cases. Among healthy and immunocompromised children,
      prophylaxis with acyclovir was effective and well-tolerated.

PMID- 25996323
TI  - Characteristics of cerebrospinal fluid (CSF) among children with
      ventriculoperitoneal shunt infections.
AB  - A common (5%) complication of cerebrospinal fluid (CSF) shunt systems is
      infection. CSF cytochemical findings have been used to choose the initial
      empirical antimicrobial treatment. The objective was to evaluate the results of
      cytochemical and microbiological analyses of CSF samples obtained from children
      with pyogenic ventriculitis associated to ventriculoperitoneal shunt systems.
      This was a retrospective, descriptive and analytical study. Thirty-two cases of
      pyogenic ventriculitis were included; Gram-positive bacteria were predominant in
      26 cases (81.25%); the rest corresponded to Gram-negative bacteria. There were no
      statistically significant differences for the studied outcome variables (CSF
      cellularity, glucose and protein levels). CONCLUSION: Gram-positive bacteria were
      widely predominant as a cause of pyogenic ventriculitis associated to the
      surgical procedure. CSF characteristics show a high heterogeneity and were not
      associated to the type of microorganism in this studied sample.

PMID- 25996324
TI  - [Prenatal and postnatal nutrition: long term impact on health].
AB  - Nutrition in early stages of life is one of the most influential environmental
      factors for the good development of organs and systems and the wellbeing of the
      child. Epigenetic mechanisms can explain how prenatal and postnatal nutrition
      affects genes expression with the subsequent risk of immune and metabolic
      diseases. The objective of this paper is to update the knowledge of the role the
      nutritional status and dietary practices of pregnant women and the child's
      feeding patterns over the first year of life have in the risk of future diseases.

PMID- 25996325
TI  - [A Recreation Room for adolescents who are hospitalized at a tertiary-care
      Center: Care Program for Hospitalized Adolescents].
AB  - Hospital admission is a high-impact event in children. Adolescence is a critical
      and complex period of human development that may be adversely affected by
      hospitalization. At the Garrahan Hospital, where adolescents account for more
      than 30% of inpatients, a program for comprehensive care of adolescents was set
      up in 2008 with a special focus on their specific needs. As a part of this
      program, the aim of the Recreation Room for Hospitalized Adolescents is to
      provide a friendly environment to reduce stress and anxiety and to facilitate the
      learning of healthy behaviors, under the permanent care of nurses and medical
      doctors. Interventions in health, leisure time, education, and emotional care are
      effective in diminishing the negative impact of hospitalization and prevent risk
      behaviors. Our objective was to report our experience in the Recreation Room for
      Hospitalized Adolescents. 

PMID- 25996326
TI  - [Considerations from a Children's Hospital Bioethics Committee about diagnosis
      and treatment of the disorders of sex development].
AB  - Through history, diagnosis and management of sex development disorders has been
      very difficult due to the significant impact on affected children, their families
      and care takers, representing a great challenge to healthcare professionals.
      Nowadays, there is significant debate regarding these children's care and
      outcome. This discussion is not only a medical issue, but it also includes legal
      and ethical matters. The Bioethics Committee of the "Hospital de Ninos Ricardo
      Gutierrez" has been considering this conflict and discussing its different
      aspects. Here we share our beliefs and opinions taking into account that they
      should not be considered the only and whole truth. There is an open debate in
      which all involved people should participate. 

PMID- 25996327
TI  - [The Convention on the Rights of the Child in Action: the Hospital Garrahan's
      experience through mainstreaming the rights approach into health care].
AB  - INTRODUCTION: Daily practice shows the lack of knowledge that health workers have
      about child rights, in terms of learning about local and international
      regulations and frameworks, as well as the persistence of paternalistic attitudes
      towards children and adolescents that attend health care services. The Convention
      on the Rights of the Child founded a new paradigm to consider the child as a
      subject of rights. OBJECTIVE: To report the experience of professional training
      for the mainstreaming of child rights in the Hospital J. P. Garrahan.
      METHODOLOGY: Courses for all areas of the institution were implemented. Teaching
      procedures and assessment criteria were defined through the formulation and
      implementation of projects, interdisciplinary work, professional accreditation
      and progressive institutionalization. RESULTS: Five training courses were held
      since 2009. 201 students were enrolled, 50.2% of which finished. The level of
      satisfaction with the proposal in terms of knowledge and expectations showed
      satisfactory results. The challenges and opportunities in the implementation are
      discussed. CONCLUSION: Incorporating the human rights approach implies an
      institution cultural change. The continuing education in the rights of children
      will contribute to achieving this goal.

PMID- 25996328
TI  - [Recommendations for the management of the child with allergic diseases at
      school].
AB  - Allergic diseases cause great impact on the health related quality of life in
      children and adolescents, resulting in increased school absenteeism and
      deficiencies in school performance. Although the bibliographic framework on
      allergic diseases is wide, in our country, there are no guidelines for proper
      management of the allergic child at school. It is necessary to establish
      guidelines for coordinated action among the educational community, the families,
      the pediatrician, the health team and governmental and non-governmental
      authorities. This position paper aims to provide information about the impact of
      allergic diseases on school activities, establish standards of competence of the
      various stakeholders at school and consider the legal framework for the
      intervention of the school staff about the child with allergies at school. 

PMID- 25996330
TI  - [In Process Citation].

PMID- 25996329
TI  - [Considerations about the infant safe sleep: Executive summary].

PMID- 25996331
TI  - [Wiskott-Aldrich syndrome: Case report].
AB  - The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency, with
      an estimated incidence of 3.5 to 5.2 cases per million males. It is characterized
      by immunodeficiency, microthrombocytopenia and eczema. We present a 5-year-old
      Hispanic male, with a medical history of numerous infectious diseases,
      compromised health, chronic malnutrition, language delay and failure to thrive.
      An infrequent mutation in the Wiskott-Aldrich syndrome gene was found.

PMID- 25996332
TI  - [Silver-Russell syndrome (hemihypertrophy) and cor triatriatum in a newborn].
AB  - Hemihypertrophy syndrome and cor triatriatum are extremely rare pathologies.
      Hemihypertrophy is defined as complete or partial overgrowth of one of the
      hemibodies. Cor triatriatum is a congenital heart disease characterized by a
      membrane which separates the left atrium into two chambers; if that membrane has
      a restrictive hole, it causes obstruction to blood passage from the pulmonary
      veins into the left ventricle causing hypertension and pulmonary edema. In this
      context, the patent ductus arteriosus can act as a means of decompression of the
      pulmonary circuit, because it allows the blood passage from the pulmonary artery
      to the aorta. We report a patient with Silver-Rusell syndrome (hemihypertrophy),
      cor triatriatum and ductus arteriosus with reverse flow. To our knowledge, this
      association of rare pathologies and this clinical presentation have not been
      described previously. 

PMID- 25996333
TI  - [Symptomatic cytomegalovirus infection through breastfeeding in a 45 days old
      boy].
AB  - Postnatal infection or acquired cytomegalovirus in the newborn is transmitted by
      maternal cervical secretions at birth, breastfeeding, blood transfusion or
      biological fluids. Breast milk is the main source of infection. Clinical
      manifestations depend on the gestational age and birth weight, premature and low
      birth weight newborn being more vulnerable. Postnatal infection usually resolves
      spontaneously without antiviral treatment; the risk of long-term sequelae is
      lower than in congenital infection. We describe the case of a 45 days old male
      patient, term newborn appropriate for gestational age, with a very rare condition
      characterized by severe thrombocytopenia secondary to postnatal cytomegalovirus
      infection. We detail its symptoms, clinical evolution, diagnosis and treatment
      employed. 

PMID- 25996334
TI  - [Duchenne muscular dystrophy: Case of atypical presentation and early diagnosis].
AB  - INTRODUCTION: Duchenne muscular dystrophy is the most common form of muscular
      dystrophy, with an incidence of 1/3300 male live births and a prevalence rate in
      the total population of 3/100000 individuals. It is often hereditary (X-linked
      recessive) but sporadic cases are also frequent. The average age at diagnosis is
      4.83 years but an early diagnosis is possible. CLINICAL CASE: An 18-month male
      infant in ambulatory study for failure to thrive and malnutrition was admitted in
      our hospital for respiratory problems. Hypertransaminasemia without other data of
      hepatic involvement in addition to hypotonia detected in the examination oriented
      diagnosis towards myopathy, confirmed by elevated creatine kinase and
      electromyogram. The genetic study for Duchenne muscular dystrophy was negative.
      Mutations were not detected. Muscle biopsy showed complete absence of dystrophin.
      A more sensitive genetic study showed a previously undescribed mutation.

PMID- 25996335
TI  - [Atypical presentation of Gorham-Stout syndrome: Case report].
AB  - Gorham-Stout syndrome is an extremely rare pathology, of unknown etiology. It is
      characterized by proliferation of vascular channels that causes destruction and
      reabsorption of the bone matrix. We present a nine year-old male patient with an
      acute episode characterized by fever, chest pain, respiratory distress and
      dyspnea. The patient was submitted to computed tomography scan and a biopsy. The
      findings in the biopsy were multiple lytic lesions, osteolysis, and a mediastinal
      lymphangioma (lymphangiomatosis). The diagnosis was Gorham-Stout syndrome with
      atypical presentation. 

PMID- 25996336
TI  - Neonatal arterial thromboembolism and limb loss following respiratory distress
      syndrome: Case report.
AB  - Thromboembolic disease in newborn infants is a serious problem. The most
      important risk factors are iatrogenic factors, including indwelling umbilical
      catheters or central catheters. Other risk factors include asphyxia, dehydration,
      sepsis, cardiac disease, respiratory distress syndrome (RDS), disseminated
      intravascular coagulation, congenital thrombophilia (i.e., protein C or protein S
      deficiency), maternal diabetes mellitus, and passive transfer of maternal
      antiphospholipid antibodies. Neonates are more vulnerable to thrombosis than
      adults due to their reduced fibrinolytic capability. We describe a case of a 1
      day-old female newborn with arterial thromboembolism in the lower leg without a
      central line catheter. The thromboembolismin in this case was associated with
      RDS. The infant underwent thrombolysis, anticoagulation therapy, and surgical
      thrombectomy. The leg of the infant was subsequently amputated below the knee.
      The case is described here with a brief review of relevant literatures. 

PMID- 25996337
TI  - Adrenal hemorrhage presenting as a scrotal hematoma in the newborn: A case
      report.
AB  - Neonatal adrenal hemorrhage is uncommon. It is present in 0,2% of newborns. Ten
      percent of the cases occur bilaterally. It can be associated with birth trauma,
      large birth weight, or neonatal course complicated by hypoxia and asphyxia,
      hypotension, or coagulopathy. Scrotal hematoma is an extremely rare manifestation
      of NAH. Most patients present scrotal swelling with bluish discolouration.
      Scrotal swelling with/without bluish discoloration in newborns may result from
      different causes. We report an unusual case of neonatal adrenal hemorrhage
      secondary to perinatal asphyxia, associated with SH. Neonatal adrenal hemorrhage
      and scrotal hematoma were diagnosed by ultrasonography and treated by
      conservative treatment, avoiding unnecessary surgical exploration.

PMID- 25996338
TI  - [Lyme disease in Pediatrics: different faces, the same disease. Cases series].
AB  - Lyme disease is caused by Borrelia burgdorferi infection which is transmitted by
      Ixodes ricinus. Erythema migrans, a rash spreading from the site of a tick bite,
      is the earliest and most common manifestation of the disease. If untreated, late
      manifestations of disseminated disease, mainly neurological and musculoskeletal,
      may occur. Serologic studies are usually negative in early stages and are not
      necessary to confirm the diagnosis in cases of erythema migrans. Laboratory
      confirmation is needed for disseminated disease. Most presentations, including
      facial nerve palsy, can be treated with oral antibiotics. Ceftriaxone is
      recommended in other cases of neuroborreliosis. Four cases of Lyme disease in
      children are reported to illustrate the different presentations of this disease
      and its management in children.

PMID- 25996339
TI  - [Validation of a clinical prediction rule for pediatric abusive head trauma].

PMID- 25996340
TI  - Making a diagnosis of psoriasis requires knowledge, experience and expertise.

PMID- 25996341
TI  - Thermal Conductivity of Polymer-Based Composites with Magnetic Aligned Hexagonal
      Boron Nitride Platelets.
AB  - Hexagonal boron nitride (hBN) platelets are widely used as the reinforcing
      fillers for enhancing the thermal conductivity of polymer-based composites. Since
      hBN platelets have high aspect ratio and show a highly anisotropic thermal
      property, the thermal conductivity of the hBNs-filled composites should be
      strongly associated with the platelets' orientation. However, the orientation
      effect has been explored less frequently due to the technical difficulties in
      precontrol of the platelets' orientation in the polymer matrix. In this paper, we
      report the use of magnetic fields to assemble the platelets into various
      microstructures and to study the thermal conductivities of the designed
      composites. The experimental results showed that thermal conductivities are
      dramatically different among these composites. For instance, the thermal
      conductivities of the composites with platelets oriented parallel and
      perpendicular to the heat flux direction are respectively 44.5% higher and 37.9%
      lower than that of unaligned composites at the volume fraction of 9.14%. The
      results were also analyzed by a theoretical model. The model suggests that the
      orientation of the hBN platelets is the main reason for the variance in the
      thermal conductivity. 

PMID- 25996342
TI  - Measurement and monitoring of nausea severity in emergency department patients: a
      comparison of scales and exploration of treatment efficacy outcome measures.
AB  - OBJECTIVES: The objective was to investigate the correlation of the visual analog
      scale (VAS) and numeric rating scale (NRS) for nausea severity measurement and to
      explore options for improved reporting of antiemetic efficacy trial results.
      METHODS: This was a multicenter observational study of adult emergency department
      (ED) patients with nausea. Participants rated severity at enrollment and 30
      minutes posttreatment using an adjectival scale, a VAS, and an NRS.
      Posttreatment, patients described symptom change and rated satisfaction. RESULTS:
      Ratings were performed by 258 patients. Both the VAS (0 to 100 mm) and the NRS (0
      to 10) discriminated between adjectival severity categories. Median ratings with
      interquartile ranges (IQRs) were "severe" VAS 90.5 (IQR = 79 to 97) and NRS 9
      (IQR = 8 to 9), "moderate" VAS 59 (IQR = 48 to 71) and NRS 6 (IQR = 5 to 7),
      "mild" VAS 34 (IQR = 25 to 49) and NRS 4 (IQR = 3 to 5), and "none" VAS 5 (IQR =
      0 to 9) and NRS 0 (IQR = 0 to 1). Correlation between the VAS and NRS was high
      (0.83, Spearman). For the VAS, median mm (IQR) reductions for posttreatment
      change were "a lot less" -42 (IQR = -26 to -58.5), "a little less" -20.5 (IQR = 
      11 to -33), "the same" -2 (IQR = -8 to 3.5), "a little more" 14 (IQR = -2 to 22),
      and "a lot more" 17 (IQR = 6 to 23) and for satisfaction were "very satisfied" 
      45 (IQR = -27 to 63), "satisfied" -27 (IQR = -13 to 46), "unsure" -15 (IQR = -3
      to -24), "dissatisfied" 4.5 (IQR = -5.5 to 13.5), and "very dissatisfied" 8.5
      (IQR = 0 to 23). A VAS cutoff of >=-5 mm detected symptom improvement with
      sensitivity 91.6% (95% CI = 86.7% to 95.1%), specificity 72.1% (95% CI = 59.9% to
      82.3%), and positive predictive value 90.2% (95% CI = 85.1% to 94.0%).
      CONCLUSIONS: The VAS and NRS correlate highly. A VAS cutoff level of >=-5 mm was
      a good predictor of symptom improvement, suggesting that its inclusion as an
      outcome measure would enhance reporting in antiemetic efficacy trials.

PMID- 25996343
TI  - Theoretical Study of Proton Coupled Electron Transfer Reactions: The Effect of
      Hydrogen Bond Bending Motion.
AB  - We investigate theoretically the effect of hydrogen bond bending motion on the
      proton coupled electron transfer (PCET) reaction, using a model system where an
      intramolecular hydrogen-bonded phenol group is the proton donor. It is shown
      that, in a two-dimensional (2D) model of the PCET reaction, the bending and
      stretching vibrational motions are separated, and due to the hydrogen bond
      configuration and anharmonicity of the potential energy surface, the bending
      vibration can play a role in the PCET reaction. The results are also compared
      with two different sets of one-dimensional models (1D-linear and 1D-curved). Due
      to contributions of the bending motion, the rate constants in the 2D model are
      larger than those in the 1D-linear model, although the differences between the
      total rate constants and KIEs for 2D and 1D models are not major. Results from
      the 1D-curved model lie between the 2D- and 1D-linear models, indicating that it
      can include some effect of bending motion in reducing the potential energies
      along the reaction path. 

PMID- 25996344
TI  - Bone grafting materials in critical defects in rabbit calvariae. A systematic
      review and quality evaluation using ARRIVE guidelines.
AB  - AIMS: To perform a systematic literature review of the regenerative potential of
      bone substitutes used to fill critical size defects (CSDs) in rabbit calvariae;
      to determine the quality of the included studies using ARRIVE guidelines.
      MATERIAL AND METHODS: An Internet search was performed in duplicate using
      MEDLINE, PubMed and Google Scholar databases (without restrictions on publication
      date) for studies reporting the regenerative potential of bone substitutes in
      CSDs in rabbit calvariae. Four parameters were analyzed by histomorphometry: new
      bone formation (NB); defect closure (DC); residual graft (RG); and connective
      tissue (CT). Animal Research Reporting in In Vivo Experiments (ARRIVE) guidelines
      (a list of 20 aspects for scoring texts and ensuring comparison between different
      experimental studies in animals) were used to evaluate the quality of the
      selected works. RESULTS: Twenty-one manuscripts were included. CSDs with 15 mm
      were predominant (57.14%). Only one study described the four histomorphometric
      parameters. NB formation was analyzed in 15 studies (71.42%) and was higher for
      particulate autogenous bone grafts (range 52.1-82%) after 12 weeks. DC was
      evaluated in six studies (28.57%) and was higher for fragmented adipose tissue
      grafts (range 53.33-93.33%) after 12 weeks. RG was evaluated in four studies
      (19.04%) and was higher for hydroxyapatite/beta-tricalcium phosphate grafts with
      silica (HA/beta-TCP + Si) (range 35.78-47.54%) at 12 weeks. CT was evaluated in
      two studies (9.5%) and was higher for HA/beta-TCP + membrane (44.2%) at 12 weeks.
      Quality evaluation identified three items (title, introduction/objectives and
      experimental procedure) (15%) with excellent scores, 10 items (abstract,
      introduction/background, methods/ethical statement, experimental animals,
      experimental outcomes, statistics, results/baseline data, outcome/estimation and
      discussion interpretation/scientific implications) (50%) with average scores, and
      seven items (housing and husbandry, sample size, allocation, numbers analyzed,
      adverse effects, general applicability/relevance and funding) (35%) obtained poor
      scores. Only one manuscript obtained a quality evaluation considered as
      excellent. CONCLUSIONS: Autogenous bone grafts increase NB. DC is enhanced by the
      use of fragmented adipose tissue. RG remains in the defect for longer when
      hydroxyapatite/beta-tricalcium phosphate with silica is used, and more CT can be
      expected when hydroxyapatite/beta-tricalcium phosphate with silica grafts are
      covered by a membrane. The addition of stem cells of different origins to
      grafting materials enhances bone formation in early healing periods. The ARRIVE
      guidelines are still insufficiently used and the overall quality of studies
      remains low.

PMID- 25996345
TI  - Rough hypercuboid based supervised clustering of miRNAs.
AB  - The microRNAs are small, endogenous non-coding RNAs found in plants, animals, and
      some viruses, which function in RNA silencing and post-transcriptional regulation
      of gene expression. It is suggested by various genome-wide studies that a
      substantial fraction of miRNA genes is likely to form clusters. The coherent
      expression of the miRNA clusters can then be used to classify samples according
      to the clinical outcome. In this regard, a new clustering algorithm, termed as
      rough hypercuboid based supervised attribute clustering (RH-SAC), is proposed to
      find such groups of miRNAs. The proposed algorithm is based on the theory of
      rough set, which directly incorporates the information of sample categories into
      the miRNA clustering process, generating a supervised clustering algorithm for
      miRNAs. The effectiveness of the new approach is demonstrated on several publicly
      available miRNA expression data sets using support vector machine. The so-called
      B.632+ bootstrap error estimate is used to minimize the variability and
      biasedness of the derived results. The association of the miRNA clusters to
      various biological pathways is also shown by doing pathway enrichment analysis. 

PMID- 25996347
TI  - Should universities play a greater role in the delivery of emergency medicine
      specialty education and training? Yes.

PMID- 25996352
TI  - Why and how do we classify von Willebrand disease?

PMID- 25996351
TI  - Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with
      ulcerative colitis and Crohn's disease.
AB  - BACKGROUND: Vedolizumab, an anti-alpha(4)beta(7) integrin monoclonal antibody
      (mAb), is indicated for treating patients with moderately to severely active
      ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb
      concentrations have been associated with greater efficacy in inflammatory bowel
      disease, understanding determinants of vedolizumab clearance may help to optimise
      dosing. AIMS: To characterise vedolizumab pharmacokinetics in patients with UC
      and CD, to identify clinically relevant determinants of vedolizumab clearance,
      and to describe the pharmacokinetic-pharmacodynamic relationship using population
      modelling. METHODS: Data from a phase 1 healthy volunteer study, a phase 2 UC
      study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic
      analysis for repeated measures was conducted using nonlinear mixed effects
      modelling. Results from the base model, developed using extensive phase 1 and 2
      data, were used to develop the full covariate model, which was fit to sparse
      phase 3 data. RESULTS: Vedolizumab pharmacokinetics was described by a 2
      compartment model with parallel linear and nonlinear elimination. Using reference
      covariate values, linear elimination half-life of vedolizumab was 25.5 days;
      linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central
      compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment
      volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35%
      for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and
      body weight values were identified as potential clinically important predictors
      of CL(L). CONCLUSIONS: Population pharmacokinetic parameters were similar in
      patients with moderately to severely active UC and CD. This analysis supports use
      of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers:
      NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI
      3).

PMID- 25996353
TI  - Primary aspergillosis of the kidney in systemic lupus erythematosus and positron
      emission tomography-computed tomography.
AB  - Primary aspergillosis of the kidney is a rare complication of immunosuppression
      in systemic lupus erythematosus. Symptoms can be insidious and can mimic
      malignancies, such as lymphomas. Herein, we report a case of a woman with
      systemic lupus erythematosus with recent history of lymphoma, who presented with
      a history of prolonged pyrexia without localizing symptoms. Repeat biopsy of the
      kidneys was crucial in obtaining histological diagnosis, and this was aided by
      findings on positron emission tomography - computed tomography.

PMID- 25996354
TI  - Structure and Dynamics of the Acidosis-Resistant A162H Mutant of the Switch
      Region of Troponin I Bound to the Regulatory Domain of Troponin C.
AB  - Intracellular acidosis lowers the Ca2+ sensitivity of cardiac muscle, which
      results in decreased force generation, decreased cardiac output, and, eventually,
      heart failure. The A162H mutant of cardiac troponin I in the thin filament turns
      the heart acidosis-resistant. Physiological and structural studies have provided
      insights into the mechanism of protection by the A162H substitution; however, the
      effect of other native residues of cardiac troponin I is not fully understood. In
      this study, we determined the structure of the A162H mutant of the switch region
      of cardiac troponin I bound to the regulatory domain of troponin C at pH 6.1, and
      the dynamics as a function of pH, by NMR spectroscopy to evaluate the changes
      induced by protonation of A162H. The results indicate that A162H induces a
      transitory curved conformation on troponin I that promotes contraction, but it is
      countered by residue E164 to ensure proper relaxation. Our model explains the
      absence of diastolic impairment in the gain-of-function phenotype induced by the
      A162H substitution as well as the effects of a variety of mutants studied
      previously. The description of this mechanism underlines the fine quality of
      regulation on cardiac muscle contraction and anticipates pharmacological agents
      that induce modest changes in the contraction-relaxation equilibrium to produce
      marked effects in cardiac performance.

PMID- 25996355
TI  - A Plan for Academic Biobank Solvency-Leveraging Resources and Applying Business
      Processes to Improve Sustainability.
AB  - Researcher-initiated biobanks based at academic institutions contribute valuable
      biomarker and translational research advances to medicine. With many legacy banks
      once supported by federal funding, reductions in fiscal support threaten the
      future of existing and new biobanks. When the Brain Bank at Duke University's
      Bryan Alzheimer's Disease Center (ADRC) faced a funding crisis, a collaborative,
      multidisciplinary team embarked on a 2-year biobank sustainability project
      utilizing a comprehensive business strategy, dedicated project management, and a
      systems approach involving many Duke University entities. By synthesizing and
      applying existing knowledge, Duke Translational Medicine Institute created and
      launched a business model that can be adjusted and applied to legacy and start-up
      academic biobanks. This model provides a path to identify new funding mechanisms,
      while also emphasizing improved communication, business development, and a focus
      on collaborating with industry to improve access to biospecimens. Benchmarks for
      short-term Brain Bank stabilization have been successfully attained, and the
      evaluation of long-term sustainability metrics is ongoing. 

PMID- 25996356
TI  - Lymphangioma Presenting as Cardiac Tamponade in a Child.
AB  - Lymphangiomas are hamartomatous malformations, which are commonly encountered in
      children. Intrapericardial lymphangioma is exceptionally rare. We present a case
      of an intrapericardial lymphangioma in a child presenting with cardiac tamponade.

PMID- 25996357
TI  - Oxidative shift in tissue redox potential increases beat-to-beat variability of
      action potential duration.
AB  - Profound changes in tissue redox potential occur in the heart under conditions of
      oxidative stress frequently associated with cardiac arrhythmias. Since beat-to
      beat variability (short term variability, SV) of action potential duration (APD)
      is a good indicator of arrhythmia incidence, the aim of this work was to study
      the influence of redox changes on SV in isolated canine ventricular
      cardiomyocytes using a conventional microelectrode technique. The redox potential
      was shifted toward a reduced state using a reductive cocktail (containing
      dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were
      initiated by superfusion with H2O2. Redox effects were evaluated as changes in
      "relative SV" determined by comparing SV changes with the concomitant APD
      changes. Exposure of myocytes to the reductive cocktail decreased SV
      significantly without any detectable effect on APD. Application of H2O2 increased
      both SV and APD, but the enhancement of SV was the greater, so relative SV
      increased. Longer exposure to H2O2 resulted in the development of early
      afterdepolarizations accompanied by tremendously increased SV. Pretreatment with
      the reductive cocktail prevented both elevation in relative SV and the
      development of afterdepolarizations. The results suggest that the increased beat
      to-beat variability during an oxidative stress contributes to the generation of
      cardiac arrhythmias. 

PMID- 25996358
TI  - Procedural Outcomes and Survival After Catheter Ablation of Ventricular
      Tachycardia in Relation to Electroanatomical Substrate in Patients With
      Nonischemic-Dilated Cardiomyopathy: The Role of Unipolar Voltage Mapping.
AB  - INTRODUCTION: In patients with ischemic cardiomyopathy the size of bipolar low
      voltage areas (LVA) in electroanatomical maps (EAM) was associated with poorer
      outcomes after catheter ablation (CA) of ventricular tachycardia (VT). However,
      the effect of LVA size on the survival after VT ablation in patients with
      nonischemic dilated cardiomyopathy (NIDCM) has not been studied. METHODS AND
      RESULTS: In 55 patients with NIDCM (48 male, age 61 +/- 16 years, ejection
      fraction 32 +/- 13%) an EAM to delineate the bipolar and unipolar LVAs was
      performed in 52 (94.5%) patients endocardially, in 24 (43.6%) patients
      epicardially, and in 21 (38.2%) patients on both surfaces. Additionally,
      activation mapping of the VT was possible in 22 (40%) patients. CA with lines
      transecting the scar and targeting late potentials was performed in all patients.
      Complete VT noninducibility at the end was achieved in 40 (72.7%) patients.
      During the median follow-up of 22 (interquartile range IQR 6, 34) months, VT
      recurrences were observed in 30 (54.5%) and cardiac death in 14 (25.5%) patients.
      The ROC analysis revealed that the size of endocardial unipolar LVA (<8.3 mV) was
      associated with cardiac death (AUC 0.89, 95% CI 0.79-0.98, P <0.0001). UVA = 145
      cm2 discriminates for cardiac death with 83% sensitivity and 78% specificity.
      Endocardial UVA > 145 cm2 was a predictor for cardiac death (adjusted HR = 6.9; P
      = 0.014) and UVA >= 54% (of total endocardial LV surface) for VT recurrence
      (adjusted HR = 3.5; P = 0.016). CONCLUSION: The size of endocardial unipolar LVA
      (<8.3 mV) was a strong and independent predictor for cardiac mortality and VT
      recurrence in patients with NIDCM.

PMID- 25996359
TI  - Application of Heavy Metal Rich Tannery Sludge on Sustainable Growth, Yield and
      Metal Accumulation by Clarysage (Salvia sclarea L.).
AB  - A field experiment was conducted to evaluate the effective utilization of tannery
      sludge for cultivation of clarysage (Salvia sclarea) at CIMAP research farm,
      Lucknow, India during the year 2012-2013. Six doses (0, 20, 40, 60, 80, 100 tha(
      1)) of processed tannery sludge were tested in randomised block design with four
      replications. Results revealed that maximum shoot, root, dry matter and oil yield
      were obtained with application of 80 tha(-1)of tannery sludge and these were 94,
      113 and 61% higher respectively, over control. Accumulation of heavy metals (Cr,
      Ni, Fe, Pb) were relatively high in shoot portion of the plant than root. Among
      heavy metals, magnitude of chromium accumulation was higher than nickel, iron and
      lead in shoot as well as in root. Linalool, linalyl acetate and sclareol content
      in oil increased by 13,8 and 27% respectively over control, with tannery sludge
      application at 80 tha(-1). Heavy metals such as chromium, cadmium and lead
      content reduced in postharvest soil when compared to initial status. Results
      indicated that clarysage (Salvia sclarea) can be grown in soil amended with 80
      tha(-1)sludge and this can be a suitable accumulator of heavy metals for
      phytoremediation of metal polluted soils. 

PMID- 25996360
TI  - Gait Characteristics, Symptoms, and Function in Persons With Hip Osteoarthritis:
      A Longitudinal Study With 6 to 7 Years of Follow-up.
AB  - STUDY DESIGN: Longitudinal laboratory study. OBJECTIVES: (1) To compare gait
      characteristics between individuals with early-stage hip osteoarthritis who
      underwent total hip replacement (THR) and those who did not undergo THR, and (2)
      to evaluate whether gait characteristics, function, and symptoms declined among
      individuals who did not undergo THR during a 6- to 7-year follow-up. BACKGROUND:
      The natural history of symptoms, function, and gait changes secondary to hip
      osteoarthritis, including potential differences at an early stage of disease, is
      unknown. METHODS: Forty-three individuals (mean age, 58.9 years) with
      radiographic and symptomatic hip osteoarthritis participated. Outcome measures
      included 3-D gait analysis; self-reported pain, stiffness, and function; hip
      range of motion; and the six-minute walk test. Baseline comparisons between
      individuals who later underwent THR and those who did not undergo THR were made
      using independent t tests or Mann-Whitney U tests. Comparisons of baseline
      measures and 6- to 7-year follow-up for the nonoperated individuals were
      conducted with paired-samples t tests or Wilcoxon signed-rank tests (P<.05).
      RESULTS: Twelve (27.9%) of the 43 individuals initially evaluated had not
      undergone THR at the 6- to 7-year follow-up. At baseline, these individuals had
      larger sagittal plane hip and knee joint excursions, larger joint space width,
      lower body mass index, and superior self-reported function compared with the
      individuals who later underwent THR. At the 6- to 7-year follow-up, the
      individuals who did not undergo THR exhibited no decline in gait characteristics,
      minimum joint space, or overall function. Furthermore, their self-reported pain
      had significantly decreased (P = .024). CONCLUSION: Individuals who did not
      undergo THR during a 6- to 7-year follow-up period did not exhibit a decline in
      gait, function, or symptoms compared to those who underwent THR. These findings
      are suggestive of a phenotype of hip osteoarthritis with a very slow disease
      progression, particularly in regard to pain. LEVEL OF EVIDENCE: Prognosis, level
      1b.

PMID- 25996361
TI  - Development of a Review-of-Systems Screening Tool for Orthopaedic Physical
      Therapists: Results From the Optimal Screening for Prediction of Referral and
      Outcome (OSPRO) Cohort.
AB  - STUDY DESIGN: Literature review and cross-sectional study. BACKGROUND: Direct
      access to physical therapy necessitates greater responsibility to determine
      appropriateness of care by recognizing the potential for concomitant disease or
      systemic involvement. Recent research has identified excessive variability in the
      reporting of red flag symptoms. An initial step to improve the identification of
      red flag symptoms is the development of a standardized screening tool. OBJECTIVE:
      To describe the development of a review-of-systems screening tool appropriate for
      use by orthopaedic physical therapists. METHODS: First, a red flag symptom item
      bank was compiled from a systematic literature review to allow for further
      psychometric testing and development of a screening tool. Second, physical
      therapists in 11 outpatient clinics recruited patients presenting with primary
      complaints of neck, shoulder, low back, or knee pain. Patients completed the red
      flag symptom item bank and standard questionnaires for comorbidities, negative
      mood, quality of life, pain, and function. The development of the screening tool
      involved identifying and combining different 3-item sets that characterized the
      highest number of patients reporting at least 1 positive symptom response
      (operationally defined as "red flag symptom responder"). RESULTS: The literature
      search yielded 103 studies that met the inclusion criteria, and the final item
      bank consisted of 97 items representing 8 body systems. Four hundred thirty-one
      patients with primary complaints of neck (n = 93), shoulder (n = 108), low back
      (n = 119), or knee (n = 111) disorders contributed to the cross-sectional study.
      The number of red flag symptom responders was 393 of 431 (91.2%). These patients
      were older, more likely to be female, had lower income, and were more likely to
      report neck or back pain (all, P<.05). A 10-item review-of-systems screening tool
      correctly identified 372 of 393 (94.7%) responders, and a 23-item version
      identified all 393 (100%) responders. The review-of-systems screening tools and
      the complete 97-item bank had similar correlations with concurrent clinical
      measures, except for depressive symptoms. CONCLUSION: Concise red flag symptom
      identification appears to be feasible in outpatient orthopaedic physical therapy
      settings. Future research will determine how this review-of-systems screening
      tool needs refinement for different patient populations and whether it predicts
      clinical outcomes or the need for referral to other providers.

PMID- 25996362
TI  - Conservative Treatment of Subacute Proximal Hamstring Tendinopathy Using
      Eccentric Exercises Performed With a Treadmill: A Case Report.
AB  - STUDY DESIGN: Case report. BACKGROUND: Proximal hamstring tendinopathy in runners
      is characterized by pain with passive hip flexion with the knee extended, active
      hip extension, and pain with sitting. Relatively little literature exists on the
      condition, and publications on nonsurgical treatment protocols are even more
      scarce. Surgical intervention, which comprises the majority of literature for
      treatment of this condition, is an option for cases that fail to respond to
      nonsurgical treatment. CASE DESCRIPTION: The patient was a 34-year-old, otherwise
      healthy male triathlete with unilateral proximal hamstring tendinopathy diagnosed
      by ultrasound, who had pain only with running and prolonged sitting. After he
      failed to respond to 4 weeks of eccentric knee flexion and lumbopelvic
      musculature strengthening exercises, an eccentric hip extensor strengthening
      program using a treadmill was initiated. This treadmill exercise was performed on
      a daily basis, in addition to a lumbopelvic musculature strengthening program.
      OUTCOMES: The patient noted a decrease in pain within 2 weeks of initiating the
      new exercise, and was able to return to gradual running after 4 weeks and to
      speed training after 12 weeks. He returned to competition shortly thereafter and
      had no recurrence for 12 months after the initiation of therapy. His score on the
      Victorian Institute of Sport Assessment-proximal hamstring tendons improved from
      23 on initial presentation to 83 at 12 weeks after the initiation of therapy.
      DISCUSSION: We described the management of a triathlete with subacute proximal
      hamstring tendinopathy, who responded well to nonsurgical treatment using
      eccentric hip extension strengthening using a treadmill. LEVEL OF EVIDENCE:
      Therapy, level 4.

PMID- 25996363
TI  - Risk Factors and Clinical Presentation of Cervical Arterial Dissection:
      Preliminary Results of a Prospective Case-Control Study.
AB  - STUDY DESIGN: Cross-sectional case-control study. OBJECTIVES: To identify risk
      factors and clinical presentation of individuals with cervical arterial
      dissection. BACKGROUND: Cervical arterial dissection is a common cause of stroke
      in young people and has in rare cases been associated with cervical manipulative
      therapy. The mechanism is considered to involve pre-existing arterial
      susceptibility and a precipitating event, such as minor trauma. Identification of
      individuals at risk or early recognition of a dissection in progress could help
      expedite medical intervention and avoid inappropriate treatment. METHODS:
      Participants were individuals 55 years of age or younger from the Hunter region
      of New South Wales, Australia with radiologically confirmed vertebral or internal
      carotid artery dissection and an age- and sex-matched comparison group.
      Participants were interviewed about risk factors, preceding events, and clinical
      features of their stroke. Physical examination of joint mobility and soft tissue
      compliance was undertaken. RESULTS: Twenty-four participants with cervical
      arterial dissection and 21 matched comparisons with ischemic stroke but not
      dissection were included in the study. Seventeen (71%) of the 24 participants
      with dissection reported a recent history of minor mechanical neck trauma or
      strain, with 4 of these 17 reporting recent neck manipulative therapy treatment.
      Cardiovascular risk factors were uncommon, with the exception of diagnosed
      migraine. Among the participants with dissection, 67% reported transient ischemic
      features in the month prior to their admission for dissection. CONCLUSION: Recent
      minor mechanical trauma or strain to the head or neck appears to be associated
      with cervical arterial dissection. General cardiovascular risk factors, with the
      exception of migraine, were not important risk factors for dissection in this
      cohort. Preceding transient neurological symptoms appear to occur commonly and
      may assist in the identification of this serious pathology. LEVEL OF EVIDENCE:
      Prognosis, level 4.

PMID- 25996364
TI  - The Patient-Specific Functional Scale: Its Reliability and Responsiveness in
      Patients Undergoing a Total Knee Arthroplasty.
AB  - STUDY DESIGN: A prospective cohort study, with assessments before, at 3 months
      after, and at 12 months after total knee arthroplasty (TKA). OBJECTIVES: To
      determine and compare the responsiveness and reliability of the Patient-Specific
      Functional Scale (PSFS) in patients undergoing a TKA. BACKGROUND: Reliable and
      valid measurement instruments are important to measure functional status. The
      PSFS is frequently used in several patient populations, but its methodological
      characteristics in a population of patients with TKA in the perioperative phases
      of surgery are unknown. METHODS: The PSFS, Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC), and global perceived effect (GPE) were
      administered at 3 time points in 150 patients undergoing a TKA. Correlations,
      effect sizes, and standardized response means were calculated. The PSFS was
      administered twice to assess its reliability in terms of intraclass correlation
      coefficients and limits of agreement. RESULTS: The correlation coefficients
      between the PSFS and WOMAC at 3 months and 1 year were 0.41 and 0.48,
      respectively; those between the PSFS and GPE were -0.37 and -0.55, respectively.
      The effect sizes of the PSFS at 3 months and 1 year were 1.71 and 2.89,
      respectively; those of the WOMAC were 1.45 and 1.64, respectively. The
      standardized response means of the PSFS at 3 months and 1 year were 0.96 and
      1.48, respectively; those of the WOMAC were 1.28 and 1.37, respectively. The
      intraclass correlation coefficients ranged between 0.73 and 0.86. The systematic
      error was between 0.12 and 0.54. The limits of agreement ranged from +/-2.17 to
      +/-2.72. CONCLUSION: The reliability of the PSFS is good. Its responsiveness is
      high, especially in the long term. However, the PSFS cannot be used
      interchangeably with the WOMAC in the immediate postoperative period.

PMID- 25996365
TI  - Thoracic Spine Manipulation in Individuals With Subacromial Impingement Syndrome
      Does Not Immediately Alter Thoracic Spine Kinematics, Thoracic Excursion, or
      Scapular Kinematics: A Randomized Controlled Trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To determine if thoracic
      spinal manipulative therapy (SMT) alters thoracic kinematics, thoracic excursion,
      and scapular kinematics compared to a sham SMT in individuals with subacromial
      impingement syndrome, and also to compare changes in patient-reported outcomes
      between treatment groups. BACKGROUND: Prior studies indicate that thoracic SMT
      can improve pain and disability in individuals with subacromial impingment
      syndrome. However, the mechanisms underlying these benefits are not well
      understood. METHODS: Participants with shoulder impingement symptoms (n = 52)
      were randomly assigned to receive a single session of thoracic SMT or sham SMT.
      Thoracic and scapular kinematics during active arm elevation and overall thoracic
      excursion were measured before and after the intervention. Patient-reported
      outcomes measured were pain (numeric pain-rating scale), function (Penn Shoulder
      Score), and global rating of change. RESULTS: Following the intervention, there
      were no significant differences in changes between groups for thoracic kinematics
      or excursion, scapular kinematics, and patient-reported outcomes (P>.05). Both
      groups showed an increase in scapular internal rotation during arm raising (mean,
      0.9 degrees ; 95% confidence interval [CI]: 0.3 degrees , 1.6 degrees ; P = .003)
      and lowering (0.8 degrees ; 95% CI: 0.0 degrees , 1.5 degrees ; P = .041), as
      well as improved pain reported on the numeric pain-rating scale (1.2 points; 95%
      CI: 0.3, 1.8; P<.001) and function on the Penn Shoulder Score (9.1 points; 95%
      CI: 6.5, 11.7; P<.001). CONCLUSION: Thoracic spine extension and excursion did
      not change significantly following thoracic SMT. There were small but likely not
      clinically meaningful changes in scapular internal rotation in both groups.
      Patient-reported pain and function improved in both groups; however, there were
      no significant differences in the changes between the SMT and the sham SMT
      groups. Overall, patient-reported outcomes improved in both groups without
      meaningful changes to thoracic or scapular motion. LEVEL OF EVIDENCE: Therapy,
      level 1b-.

PMID- 25996367
TI  - Pre-implanted Sensory Nerve Could Enhance the Neurotization in Tissue-Engineered
      Bone Graft.
AB  - In our previous study, it was found that implanting the sensory nerve tract into
      the tissue-engineered bone to repair large bone defects can significantly result
      in better osteogenesis effect than tissue-engineered bone graft (TEBG) alone. To
      study the behavior of the preimplanted sensory nerve in the TEBG, the TEBG was
      constructed by seeding bone mesenchymal stem cells into beta-tricalcium phosphate
      scaffold with (treatment group) or without (blank group) implantation of the
      sensory nerve. The expression of calcitonin gene-related peptide (CGRP), which
      helps in the healing of bone defect in the treatment group was significantly
      higher than the blank group at 4, 8, and 12 weeks. The expression of growth
      associated protein 43 (GAP43), which might be expressed during nerve healing in
      the treatment group, was significantly higher than the blank group at 4 and 8
      weeks. The nerve tracts of the preimplanted sensory nerve were found in the
      scaffold by the nerve tracing technique. The implanted sensory nerve tracts grew
      into the pores of scaffolds much earlier than the vascular. The implanted sensory
      nerve tracts traced by Dil could be observed at 4 weeks, but at the same time, no
      vascular was observed. In conclusion, the TEBG could be benefited from the
      preimplanted sensory nerve through the healing behavior of the sensory nerve. The
      sensory nerve fibers could grow into the pores of the TEBG rapidly, and increase
      the expression of CGRP, which is helpful in regulating the bone formation and the
      blood flow. 

PMID- 25996366
TI  - Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a
      season dominated by vaccine-matched influenza B virus.
AB  - Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent
      laboratory-confirmed influenza B cases are uncommon, and few have analyzed the
      effect in preventing hospitalized cases. We have evaluated the influenza VE in
      preventing outpatient and hospitalized cases with laboratory-confirmed influenza
      in the 2012-2013 season, which was dominated by a vaccine-matched influenza B
      virus. In the population covered by the Navarra Health Service, all hospitalized
      patients with influenza-like illness (ILI) and all ILI patients attended by a
      sentinel network of general practitioners were swabbed for influenza testing, and
      all were included in a test-negative case-control analysis. VE was calculated as
      (1-odds ratio) * 100. Among 744 patients tested, 382 (51%) were positive for
      influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2).
      The overall estimate of VE in preventing laboratory-confirmed influenza was 63%
      (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74%
      (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza
      B and 43% (-45 to 78) against influenza A. The VE against virus B was 87% (52 to
      96) in hospitalized patients and 56% in outpatients (-5 to 81). Adjusted
      comparison of vaccination status between inpatient and outpatient cases with
      influenza B did not show statistically significant differences (odds ratio: 1.13;
      p = 0.878). These results suggest a high protective effect of the vaccine in the
      2012-2013 season, with no differences found for the effect between outpatient and
      hospitalized cases.

PMID- 25996369
TI  - New operational matrices for solving fractional differential equations on the
      half-line.
AB  - In this paper, the fractional-order generalized Laguerre operational matrices
      (FGLOM) of fractional derivatives and fractional integration are derived. These
      operational matrices are used together with spectral tau method for solving
      linear fractional differential equations (FDEs) of order nu (0 < nu < 1) on the
      half line. An upper bound of the absolute errors is obtained for the approximate
      and exact solutions. Fractional-order generalized Laguerre pseudo-spectral
      approximation is investigated for solving nonlinear initial value problem of
      fractional order nu. The extension of the fractional-order generalized Laguerre
      pseudo-spectral method is given to solve systems of FDEs. We present the
      advantages of using the spectral schemes based on fractional-order generalized
      Laguerre functions and compare them with other methods. Several numerical
      examples are implemented for FDEs and systems of FDEs including linear and
      nonlinear terms. We demonstrate the high accuracy and the efficiency of the
      proposed techniques. 

PMID- 25996370
TI  - Correction: Rapid stress system drives chemical transfer of fear from sender to
      receiver.

PMID- 25996368
TI  - Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and
      Barrett's Esophagus.
AB  - Gastric intestinal metaplasia (IM) is a highly prevalent preneoplastic lesion;
      however, the molecular mechanisms regulating its development remain unclear. We
      have previously shown that a population of cells expressing the intestinal stem
      cell (ISC) marker LGR5 increases remarkably in IM. In this study, we further
      investigated the molecular characteristics of these LGR5+ cells in IM by
      examining the expression profile of several ISC markers. Notably, we found that
      ISC markers-including OLFM4 and EPHB2-are positively associated with the CDX2
      expression in non-tumorous gastric tissues. This finding was confirmed in stomach
      lesions with or without metaplasia, which demonstrated that OLFM4 and EPHB2
      expression gradually increased with metaplastic progression. Moreover, RNA in
      situ hybridization revealed that LGR5+ cells coexpress several ISC markers and
      remained confined to the base of metaplastic glands, reminiscent to that of
      normal intestinal crypts, whereas those in normal antral glands expressed none of
      these markers. Furthermore, a large number of ISC marker-expressing cells were
      diffusely distributed in gastric adenomas, suggesting that these markers may
      facilitate gastric tumorigenesis. In addition, Barrett's esophagus (BE)-which is
      histologically similar to intestinal metaplasia-exhibited a similar distribution
      of ISC markers, indicating the presence of a stem cell population with intestinal
      differentiation potential. In conclusion, we identified that LGR5+ cells in
      gastric IM and BE coexpress ISC markers, and exhibit the same expression profile
      as those found in normal intestinal crypts. Taken together, these results
      implicate an intestinal-like stem cell population in the pathogenesis of IM, and
      provide an important basis for understanding the development and maintenance of
      this disease. 

PMID- 25996371
TI  - The Effects of Text Message Content on the Use of an Internet-Based Physical
      Activity Intervention in Hong Kong Chinese Adolescents.
AB  - This study examined the effects of text message content (generic vs. culturally
      tailored) on the login rate of an Internet physical activity program in Hong Kong
      Chinese adolescent school children. A convenience sample of 252 Hong Kong
      secondary school adolescents (51% female, 49% male; M age = 13.17 years, SD =
      1.28 years) were assigned to one of 3 treatments for 8 weeks. The control group
      consisted of an Internet physical activity program. The Internet plus generic
      text message group consisted of the same Internet physical activity program and
      included daily generic text messages. The Internet plus culturally tailored text
      message group consisted of the Internet physical activity program and included
      daily culturally tailored text messages. Zero-inflated Poisson mixed models
      showed that the overall effect of the treatment group on the login rates varied
      significantly across individuals. The login rates over time were significantly
      higher in the Internet plus culturally tailored text message group than the
      control group (beta = 46.06, 95% CI 13.60, 156.02; p = .002) and the Internet
      plus generic text message group (beta = 15.80, 95% CI 4.81, 51.9; p = .021) after
      adjusting for covariates. These findings suggest that culturally tailored text
      messages may be more advantageous than generic text messages on improving
      adolescents' website login rate, but effects varied significantly across
      individuals. Our results support the inclusion of culturally tailored messaging
      in future online physical activity interventions.

PMID- 25996372
TI  - Sociodemographic Differences in the Association Between Obesity and Stress: A
      Propensity Score-Matched Analysis from the Korean National Health and Nutrition
      Examination Survey (KNHANES).
AB  - Few population-based studies have used an econometric approach to understand the
      association between two cancer risk factors, obesity and stress. This study
      investigated sociodemographic differences in the association between obesity and
      stress among Korean adults (6,546 men and 8,473 women). Data were drawn from the
      Korean National Health and Nutrition Examination Survey for 2008, 2009, and 2010.
      Ordered logistic regression models and propensity score matching methods were
      used to examine the associations between obesity and stress, stratified by gender
      and age groups. In women, the stress level of the obese group was found to be
      27.6% higher than the nonobese group in the ordered logistic regression; the
      obesity effect on stress was statistically significant in the propensity score
      matched analysis. Corresponding evidence for the effect of obesity on stress was
      lacking among men. Participants who were young, well-educated, and working were
      more likely to report stress. In Korea, obesity causes stress in women but not in
      men. Young women are susceptible to a disproportionate level of stress. More
      cancer prevention programs targeting young and obese women are encouraged in
      developed Asian countries. 

PMID- 25996373
TI  - The opponent channel population code of sound location is an efficient
      representation of natural binaural sounds.
AB  - In mammalian auditory cortex, sound source position is represented by a
      population of broadly tuned neurons whose firing is modulated by sounds located
      at all positions surrounding the animal. Peaks of their tuning curves are
      concentrated at lateral position, while their slopes are steepest at the
      interaural midline, allowing for the maximum localization accuracy in that area.
      These experimental observations contradict initial assumptions that the auditory
      space is represented as a topographic cortical map. It has been suggested that a
      "panoramic" code has evolved to match specific demands of the sound localization
      task. This work provides evidence suggesting that properties of spatial auditory
      neurons identified experimentally follow from a general design principle-
      learning a sparse, efficient representation of natural stimuli. Natural binaural
      sounds were recorded and served as input to a hierarchical sparse-coding model.
      In the first layer, left and right ear sounds were separately encoded by a
      population of complex-valued basis functions which separated phase and amplitude.
      Both parameters are known to carry information relevant for spatial hearing.
      Monaural input converged in the second layer, which learned a joint
      representation of amplitude and interaural phase difference. Spatial selectivity
      of each second-layer unit was measured by exposing the model to natural sound
      sources recorded at different positions. Obtained tuning curves match well tuning
      characteristics of neurons in the mammalian auditory cortex. This study connects
      neuronal coding of the auditory space with natural stimulus statistics and
      generates new experimental predictions. Moreover, results presented here suggest
      that cortical regions with seemingly different functions may implement the same
      computational strategy-efficient coding. 

PMID- 25996374
TI  - Robot-assisted arm assessments in spinal cord injured patients: a consideration
      of concept study.
AB  - Robotic assistance is increasingly used in neurological rehabilitation for
      enhanced training. Furthermore, therapy robots have the potential for accurate
      assessment of motor function in order to diagnose the patient status, to measure
      therapy progress or to feedback the movement performance to the patient and
      therapist in real time. We investigated whether a set of robot-based assessments
      that encompasses kinematic, kinetic and timing metrics is applicable, safe,
      reliable and comparable to clinical metrics for measurement of arm motor
      function. Twenty-four healthy subjects and five patients after spinal cord injury
      underwent robot-based assessments using the exoskeleton robot ARMin. Five
      different tasks were performed with aid of a visual display. Ten kinematic,
      kinetic and timing assessment parameters were extracted on joint- and end
      effector level (active and passive range of motion, cubic reaching volume,
      movement time, distance-path ratio, precision, smoothness, reaction time, joint
      torques and joint stiffness). For cubic volume, joint torques and the range of
      motion for most joints, good inter- and intra-rater reliability were found
      whereas precision, movement time, distance-path ratio and smoothness showed weak
      to moderate reliability. A comparison with clinical scores revealed good
      correlations between robot-based joint torques and the Manual Muscle Test.
      Reaction time and distance-path ratio showed good correlation with the "Graded
      and Redefined Assessment of Strength, Sensibility and Prehension" (GRASSP) and
      the Van Lieshout Test (VLT) for movements towards a predefined position in the
      center of the frontal plane. In conclusion, the therapy robot ARMin provides a
      comprehensive set of assessments that are applicable and safe. The first results
      with spinal cord injured patients and healthy subjects suggest that the
      measurements are widely reliable and comparable to clinical scales for arm motor
      function. The methods applied and results can serve as a basis for the future
      development of end-effector and exoskeleton-based robotic assessments. 

PMID- 25996375
TI  - Immunogenicity without Efficacy of an Adenoviral Tuberculosis Vaccine in a
      Stringent Mouse Model for Immunotherapy during Treatment.
AB  - To investigate if bacterial persistence during TB drug treatment could be
      overcome by modulation of host immunity, we adapted a clinically-relevant model
      developed for the evaluation of new drugs and examined if immunotherapy with two
      adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in
      mice. Even though immunotherapy resulted in strong splenic IFN-gamma responses,
      no effect on bacterial replication in the lungs was seen. Multiplex assay
      analysis of lung samples revealed the absence of cytokine augmentation such as
      IFN-gamma, TNF-alpha and IL-2, suggesting that immunization failed to induce
      immunity in the lungs. In this model, we show that IFN-gamma levels were not
      associated with protection against disease relapse. The results obtained from our
      study raise questions regarding the traits of protective TB immunity that are
      relevant for the development of future immunotherapeutic and post-exposure
      vaccination strategies. 

PMID- 25996378
TI  - Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis.
AB  - BACKGROUND: Neonatal sepsis (NS) is a life-threatening disorder and an important
      cause of morbidity and mortality in neonates. Previous studies showed that
      interleukin 8 (IL-8) may effectively and rapidly diagnose NS. OBJECTIVE: We
      conducted the systematic review and meta-analysis to investigate the diagnostic
      value of the IL-8 in NS. METHODS: The literature was searched in PUBMED, EMBASE,
      Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October
      1998 to January 2014 using set search criteria. Each included study was evaluated
      by quality assessment of diagnostic accuracy studies tool. Two investigators
      independently extracted the data and study characteristics, and disagreements, if
      any, were resolved by consensus. Meta-disc software was used to calculate the
      pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR), I2 or
      Cochrane Q to test heterogeneity, and meta-regression to investigate the source
      of heterogeneity. Funnel plots were used to test the potential presence of
      publication bias. False-positive report probability (FPRP) was calculated to
      confirm the significance of the results. RESULTS: Eight studies (548 neonates)
      were included in this meta-analysis. The pooled sensitivity and specificity of IL
      8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis
      of NS. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) was
      21.64 and 0.8908 (Q*=0.8215), respectively. The diagnostic threshold analysis
      showed that there was no threshold effect. The meta-regression analysis showed
      the cut-off, QUADAS and onset time have no effect on the heterogeneity. The
      funnel plots showed the existence of publication bias. CONCLUSION: Meta-analysis
      showed IL-8 had a moderate accuracy (AUC=0.8908) for the diagnosis of NS. IL-8 is
      a helpful biomarker for early diagnosis of NS. However, we should combine the
      results with clinical symptoms and signs, laboratory and microbial results.

PMID- 25996379
TI  - A Central Role for JNK/AP-1 Pathway in the Pro-Oxidant Effect of Pyrrolidine
      Dithiocarbamate through Superoxide Dismutase 1 Gene Repression and Reactive
      Oxygen Species Generation in Hematopoietic Human Cancer Cell Line U937.
AB  - Pyrrolidine dithiocarbamate (PDTC) known as antioxidant and specific inhibitor of
      NF-kappaB was also described as pro-oxidant by inducing cell death and reactive
      oxygen species (ROS) accumulation in cancer. However, the mechanism by which PDTC
      indices its pro-oxidant effect is unknown. Therefore, we aimed to evaluate the
      effect of PDTC on the human Cu/Zn superoxide dismutase 1 (SOD1) gene
      transcription in hematopoietic human cancer cell line U937. We herein show for
      the first time that PDTC decreases SOD1 transcripts, protein and promoter
      activity. Furthermore, SOD1 repression by PDTC was associated with an increase in
      oxidative stress as evidenced by ROS production. Electrophoretic mobility-shift
      assays (EMSA) show that PDTC increased binding of activating protein-1 (AP-1) in
      dose dependent-manner suggesting that the MAPkinase up-stream of AP-1 is
      involved. Ectopic NF-kappaB p65 subunit overexpression had no effect on SOD1
      transcription. In contrast, in the presence of JNK inhibitor (SP600125), p65
      induced a marked increase of SOD1 promoter, suggesting that JNK pathway is up
      stream of NF-kappaB signaling and controls negatively its activity. Indeed, using
      JNK deficient cells, PDTC effect was not observed nether on SOD1 transcription or
      enzymatic activity, nor on ROS production. Finally, PDTC represses SOD1 in U937
      cells through JNK/c-Jun phosphorylation. Taken together, these results suggest
      that PDTC acts as pro-oxidant compound in JNK/AP-1 dependent-manner by repressing
      the superoxide dismutase 1 gene leading to intracellular ROS accumulation. 

PMID- 25996380
TI  - Microarray expression profiling of dysregulated long non-coding RNAs in triple
      negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) represents a collection of malignant breast
      tumors that are often aggressive and have an increased risk of metastasis and
      relapse. Long non-coding RNAs are generally defined as RNA transcripts measuring
      200 nucleotides or longer that do not encode for any protein. During the past
      decade, increasing evidence has shown that lncRNAs play important roles in
      oncogenesis and tumor suppression; however, the roles of lncRNAs in TNBC are
      poorly understood. To address this issue, we used Agilent human lncRNA microarray
      chips and bioinformatics tools, including Gene Ontology (GO) and the Kyoto
      Encyclopedia of Genes and Genomes (KEGG), to assess lncRNA expression in 3 pairs
      of TNBC tissues. A dysregulated lncRNA expression profile was identified by
      microarray and verified by qRT-PCR in 48 pairs of breast cancer subtype tissues.
      Metastasis is the major cause of cancer-related deaths, including those in TNBC,
      and the presence of dormant residual disseminated tumor cells (DTC) may be a key
      factor leading to metastasis. ANKRD30A, a potential target for breast cancer
      immunotherapy, is currently one of the most used DTC markers. Notably, we found
      the expression levels of the novel intergenic lncRNA LINC00993 to be associated
      with the expression levels of ANKRD30A. Furthermore, our qRT-PCR data indicated
      that the expression of LINC00993 was also associated with the expression of the
      estrogen receptor. In conclusion, our study identified a set of lncRNAs that were
      consistently aberrantly expressed in TNBC, and these dysregulated lncRNAs may be
      involved in the development and/or progression of TNBC. 

PMID- 25996384
TI  - Setting analytical performance specifications based on outcome studies - is it
      possible?
AB  - The 1st Strategic Conference of the European Federation of Clinical Chemistry and
      Laboratory Medicine proposed a simplified hierarchy for setting analytical
      performance specifications (APS). The top two levels of the 1999 Stockholm
      hierarchy, i.e., evaluation of the effect of analytical performance on clinical
      outcomes and clinical decisions have been proposed to be replaced by one outcome
      based model. This model can be supported by: (1a) direct outcome studies; and
      (1b) indirect outcome studies investigating the impact of analytical performance
      of the test on clinical classifications or decisions and thereby on the
      probability of patient relevant clinical outcomes. This paper reviews the need
      for outcome-based specifications, the most relevant types of outcomes to be
      considered, and the challenges and limitations faced when setting outcome-based
      APS. The methods of Model 1a and b are discussed and examples are provided for
      how outcome data can be translated to APS using the linked evidence and
      simulation or decision analytic techniques. Outcome-based APS should primarily
      reflect the clinical needs of patients; should be tailored to the purpose, role
      and significance of the test in a well defined clinical pathway; and should be
      defined at a level that achieves net health benefit for patients at reasonable
      costs. Whilst it is acknowledged that direct evaluations are difficult and may
      not be possible for all measurands, all other forms of setting APS should be
      weighed against that standard, and regarded as approximations. Better definition
      of the relationship between the analytical performance of tests and health
      outcomes can be used to set analytical performance criteria that aim to improve
      the clinical and cost-effectiveness of laboratory tests. 

PMID- 25996385
TI  - A checklist for critical appraisal of studies of biological variation.
AB  - Data on biological variation are used for many purposes in laboratory medicine
      but concern exists over the validity of the data reported in some studies. A
      critical appraisal checklist has been produced by a working group established by
      the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) to
      enable standardised assessment of existing and future publications of biological
      variation data. The checklist identifies key elements to be reported in studies
      to enable safe accurate and effective transport of biological variation data sets
      across healthcare systems. The checklist is mapped to the domains of a minimum
      data set required to enable this process. 

PMID- 25996383
TI  - Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and
      the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach.
AB  - Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of
      MCF7 cell apoptosis. The aims of the present study were to investigate the in
      vivo chemopreventive effect of FALHE in rats, to identify the contributing
      anticancer compound in FALHE and to determine its potential mechanism of action
      against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided
      into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment
      control (tamoxifen) and normal control. Breast tissues were then subjected to
      histopathological and immunohistochemical analyses. A bioassay-guided
      investigation on FALHE was performed to identify the cytotoxic compound and its
      mechanism of action through flow cytometry, real-time qPCR and western blotting
      analyses. An in vivo study showed that FALHE suppressed the expression of the
      tumor markers PCNA and Ki67. The tumor size was reduced from 2031 +/- 281 mm3 to
      432 +/- 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in
      breast tumor cells, and this was confirmed by high expression levels of Bax, p53
      and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27.
      The in vitro experimental results resulted in the isolation of polycerasoidin as
      a bioactive ingredient of FALHE with an IC50 value of 3.16 +/- 0.31 MUg/ml
      against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in
      breast cancer cells via caspase activation and changes in the mRNA and protein
      expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated
      that the treated MCF7 cells were arrested at the G1 phase, and this was
      associated with the up-regulation of p21 and p27 at both the mRNA and protein
      levels. The results of the present study reinforce further investigations
      scrutinizing the promising potential of the F. angulata chemical constituents as
      breast cancer chemopreventive agents. 

PMID- 25996386
TI  - Association of Choroidal Neovascularization and Central Serous Chorioretinopathy
      With Optical Coherence Tomography Angiography.
AB  - IMPORTANCE: Choroidal neovascularization (CNV) is a major cause of vision loss in
      chronic central serous chorioretinopathy (CSCR). Detecting CNV using fluorescein
      angiography (FA) may be challenging owing to the coexistence of features related
      to the primary diagnosis of CSCR. Optical coherence tomography angiography (OCTA)
      allows noninvasive visualization of retinal and choroidal vasculature via motion
      contrast and may contribute to the unequivocal diagnosis of CNV in this
      population. OBJECTIVE: To evaluate the sensitivity of spectral-domain OCTA in
      detecting CNV associated with chronic CSCR. DESIGN, SETTING, AND PARTICIPANTS:
      Observational cross-sectional study including 23 patients (27 eyes) who presented
      at the New England Eye Center between August 1, 2014, and November 30, 2014, with
      suspected CNV complicating chronic CSCR and underwent standard assessment for CNV
      diagnosis, including FA imaging. Participants were prospectively recruited to
      receive imaging tests using prototype OCTA software on a commercially available
      spectral-domain OCT. Orthogonal registration and the merging of 2 consecutive
      image sets were used to obtain 3 * 3-mm and 6 * 6-mm OCT angiograms centered at
      the macula. Two independent readers masked to other imaging findings performed a
      qualitative analysis on OCTA depictions of vascular flow representing CNV and the
      morphologic appearance of CNV. MAIN OUTCOMES AND MEASURES: Choroidal
      neovascularization location as well as retinal pigment epithelial detachment
      internal reflectivity and the presence of subretinal and intraretinal fluid.
      Sensitivity and specificity of OCTA in detecting CNV were estimated using FA as
      the standard examination reference. RESULTS: Choroidal neovascularization was
      diagnosed in 8 of 27 eyes (30%) based on FA imaging analysis. Optical coherence
      tomography angiography and corresponding OCT B-scans detected 100% (8 of 8) of
      these CNV lesions and correctly excluded 100% (19 of 19) of eyes with CSCR
      without CNV. Sensitivity was 100% (95% CI, 0.62-1) and specificity was 100% (95%
      CI, 0.82-1). Morphologic appearance, location, and position of the CNV relative
      to the retinal pigment epithelium and Bruch membrane were described using OCTA
      that combined flow and structural information. CONCLUSIONS AND RELEVANCE: This
      study suggests that OCT alone (OCTA and coregistered OCT B-scans) features
      sensitivity and specificity comparable with FA for the detection of CNV in eyes
      with chronic CSCR.

PMID- 25996387
TI  - 24h Urinary Protein Levels and Urine Protein/Creatinine Ratios Could Probably
      Forecast the Pathological Classification of HSPN.
AB  - This study aimed to assess the relevance of laboratory tests in Henoch-Schonlein
      purpura nephritis (HSPN) classification, and determine accurate classification
      factors. This prospective study included 694 HSPN patients who underwent
      ultrasound-guided percutaneous renal biopsy (PRB). Renal specimens were scored
      according to International Study of Kidney Disease in Children (ISKDC)
      classification. Meanwhile, blood samples were immediately collected for
      laboratory examination. The associations between laboratory parameters and HSPN
      classification were assessed. Significant differences in levels of serum Th1/Th2
      cytokines, immunoglobulins, T-lymphocyte subsets, complement, and coagulation
      markers were obtained between HSPN patients and healthy children. Interestingly,
      24h urinary protein (24h-UPRO) levels and urine protein/urine creatinine ratios
      could determine HPSN grade IIb, IIIa, and IIIb incidences, with areas under ROC
      curve of 0.767 and 0.731, respectively. At 24h-UPRO >580.35mg/L, prediction
      sensitivity and specificity were 75.2% and 70.0%, respectively. These values
      became 53.0% and 82.3%, respectively, with 24h-UPRO exceeding 1006.25mg/L. At
      urine protein/urine creatinine > 0.97, prediction sensitivity and specificity
      were 65.5% and 67.2%, respectively, values that became 57.4% and 80.0%,
      respectively, at ratios exceeding 1.2. Cell and humoral immunity, coagulation and
      fibrinolytic systems are all involved in the pathogenesis of HSPN, and type I
      hypersensitivity may be the disease trigger of HSPN. 24h-UPRO levels and urine
      protein/creatinine ratios could probably forecast the pathological classification
      of HSPN. 

PMID- 25996388
TI  - Adsorption of Rare Earths(III) Using an Efficient Sodium Alginate Hydrogel Cross
      Linked with Poly-gamma-Glutamate.
AB  - With the exploitation of rare earth ore, more and more REEs came into
      groundwater. This was a waste of resources and could be harmful to the organisms.
      This study aimed to find an efficient adsorption material to mitigate the above
      issue. Through doping sodium alginate (SA) with poly-gamma-glutamate (PGA), an
      immobilized gel particle material was produced. The composite exhibited excellent
      capacity for adsorbing rare earth elements (REEs). The amount of La3+ adsorbed on
      the SA-PGA gel particles reached approximately 163.93 mg/g compared to the 81.97
      mg/g adsorbed on SA alone. The factors that potentially affected the adsorption
      efficiency of the SA-PGA composite, including the initial concentration of REEs,
      the adsorbent dosage, and the pH of the solution, were investigated. 15 types of
      REEs in single and mixed aqueous solutions were used to explore the selective
      adsorption of REEs on gel particles. Scanning electron microscopy (SEM) and
      Fourier transform infrared (FT-IR) spectroscopy analyses of the SA and SA-PGA gel
      beads suggested that the carboxyl groups in the composite might play a key role
      in the adsorption process and the morphology of SA-PGA changed from the compact
      structure of SA to a porous structure after doping PGA. The kinetics and
      thermodynamics of the adsorption of REEs were well fit with the pseudo-second
      order equation and the Langmuir adsorption isotherm model, respectively. It
      appears that SA-PGA is useful for recycling REEs from wastewater. 

PMID- 25996389
TI  - Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on
      Pulmonary TB and DR-TB Case Finding in India.
AB  - BACKGROUND: Xpert MTB/RIF, the first automated molecular test for tuberculosis,
      is transforming the diagnostic landscape in high-burden settings. This study
      assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary
      tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. METHODS:
      This demonstration study was implemented in 18 sub-district level TB programme
      units (TUs) in India in diverse geographic and demographic settings covering a
      population of 8.8 million. A baseline phase in 14 TUs captured programmatic
      baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to
      all presumptive TB patients. We estimated changes in detection of TB and DR-TB,
      the former using binomial regression models to adjust for clustering and
      covariates. RESULTS: In the 14 study TUs, which participated in both phases,
      10,675 and 70,556 presumptive TB patients were enrolled in the baseline and
      intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%)
      bacteriologically confirmed PTB cases were detected. The implementation of Xpert
      MTB/RIF was associated with increases in both notification rates of
      bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39;
      CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among
      presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with
      the baseline strategy of selective drug-susceptibility testing only for PTB cases
      at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased
      rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin
      resistance cases detected, 1055 were retested with conventional drug
      susceptibility testing (DST). Positive predictive value (PPV) of rifampicin
      resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to
      conventional DST. CONCLUSION: Introduction of Xpert MTB/RIF as initial diagnostic
      test for TB in public health facilities significantly increased case-notification
      rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB
      case notification by fivefold.

PMID- 25996391
TI  - Interrelationship between sleep-disordered breathing and sarcoidosis.
AB  - Sleep-disordered breathing (SDB) has a high prevalence in sarcoidosis. This high
      prevalence may be the result of increased upper airways resistance from
      sarcoidosis of the upper respiratory tract, corticosteroid-induced obesity, or
      parenchymal lung involvement from sarcoidosis. OSA is a form of SDB that is
      particularly common in patients with sarcoidosis. Sarcoidosis and SDB share many
      similar symptoms and clinical findings, including fatigue, gas exchange
      abnormalities, and pulmonary hypertension (PH). Sarcoidosis-associated fatigue is
      a common entity for which stimulants may be beneficial. Sarcoidosis-associated
      fatigue is a diagnosis of exclusion that requires an evaluation for the
      possibility of OSA. Hypercapnia is unusual in a patient with sarcoidosis without
      severe pulmonary dysfunction and, in this situation, should prompt evaluation for
      alternative causes of hypercapnia, such as SDB. PH is usually mild when
      associated with OSA, whereas the severity of sarcoidosis-associated PH is related
      to the severity of sarcoidosis. PH caused by OSA usually responds to CPAP,
      whereas sarcoidosis-associated PH commonly requires the use of vasodilators.
      Management of OSA in sarcoidosis is problematic because corticosteroid treatment
      of sarcoidosis may worsen OSA. Aggressive efforts should be made to place the
      patient on the lowest effective dose of corticosteroids, which involves early
      consideration of corticosteroid-sparing agents. Because of the significant
      morbidity associated with SDB, early recognition and treatment of SDB in patients
      with sarcoidosis may improve their overall quality of life. 

PMID- 25996390
TI  - Biodistribution and Toxicity Studies of PRINT Hydrogel Nanoparticles in Mosquito
      Larvae and Cells.
AB  - Mosquito-borne diseases continue to remain major threats to human and animal
      health and impediments to socioeconomic development. Increasing mosquito
      resistance to chemical insecticides is a great public health concern, and new
      strategies/technologies are necessary to develop the next-generation of vector
      control tools. We propose to develop a novel method for mosquito control that
      employs nanoparticles (NPs) as a platform for delivery of mosquitocidal dsRNA
      molecules to silence mosquito genes and cause vector lethality. Identifying
      optimal NP chemistry and morphology is imperative for efficient mosquitocide
      delivery. Toward this end, fluorescently labeled polyethylene glycol NPs of
      specific sizes, shapes (80 nm x 320 nm, 80 nm x 5000 nm, 200 nm x 200 nm, and
      1000 nm x 1000 nm) and charges (negative and positive) were fabricated by
      Particle Replication in Non-Wetting Templates (PRINT) technology.
      Biodistribution, persistence, and toxicity of PRINT NPs were evaluated in vitro
      in mosquito cell culture and in vivo in Anopheles gambiae larvae following
      parenteral and oral challenge. Following parenteral challenge, the
      biodistribution of the positively and negatively charged NPs of each size and
      shape was similar; intense fluorescence was observed in thoracic and abdominal
      regions of the larval body. Positively charged NPs were more associated with the
      gastric caeca in the gastrointestinal tract. Negatively charged NPs persisted
      through metamorphosis and were observed in head, body and ovaries of adults.
      Following oral challenge, NPs were detected in the larval mid- and hindgut.
      Positively charged NPs were more efficiently internalized in vitro than
      negatively charged NPs. Positively charged NPs trafficked to the cytosol, but
      negatively charged NPs co-localized with lysosomes. Following in vitro and in
      vivo challenge, none of the NPs tested induced any cytotoxic effects. 

PMID- 25996397
TI  - Reorganized text.
AB  - Reorganized Text: In the Original Investigation titled "Patterns of Hospital
      Utilization for Head and Neck Cancer Care: Changing Demographics" posted online
      in the January 29, 2015, issue of JAMA Otolaryngology-Head & Neck Surgery
      (doi:10.1001 /jamaoto.2014.3603), information was copied within sections and text
      rearranged to accommodate Continuing Medical Education quiz formatting. The
      information from the topic statements of each paragraph in the Hypothesis Testing
      subsection of the Methods section was collected in a new first paragraph for that
      subsection, which reads as follows: "Several hypotheses regarding the causes of
      regionalization of HNCA care were tested using the NIS data: (1) increasing
      patient comorbidities over time, causing a shift in care to teaching institutions
      that would theoretically be better equipped to handle such increased
      comorbidities; (2) shifting of payer status; (3) increased proportion of prior
      radiation therapy; and (4) a higher fraction of more complex procedures being
      referred and performed at teaching institutions." In addition, the phrase "As
      summarized in Table3," was added to the beginning of paragraph 6 of the
      Discussion section, and the call-out to Table 3 in the middle of that paragraph
      was deleted. Finally, paragraphs 6 and 7 of the Discussion section were combined.

PMID- 25996398
TI  - Incorrect author affiliation.
AB  - Incorrect Author Affiliation: In the article titled "Effect of Human
      Papillomavirus on Patterns of Distant Metastatic Failure in Oropharyngeal
      Squamous Cell Carcinoma Treated With Chemoradiotherapy,"published online March 5,
      2015, and also in this issue of JAMA Otolaryngology-Head & Neck Surgery
      (doi:10.1001/jamaoto.2015 .136), the Author Affiliations were incorrect. That
      section should have been given as follows: "Author Affiliations: Head and Neck
      Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Trosman, Lamarre,
      Scharpf, Khan, Lorenz, Burkey); Department of Radiation Oncology, Taussig Cancer
      Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Koyfman,Ward,
      Greskovich); Department of Otolaryngology-Head and Neck Surgery, Rush University,
      Chicago, Illinois (Al-Khudari); Department of Hematology and Medical
      Oncology,Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio
      (Nwizu, Adelstein)." This article was corrected online and in print.

PMID- 25996394
TI  - Influenza A virus on oceanic islands: host and viral diversity in seabirds in the
      Western Indian Ocean.
AB  - Ducks and seabirds are natural hosts for influenza A viruses (IAV). On oceanic
      islands, the ecology of IAV could be affected by the relative diversity,
      abundance and density of seabirds and ducks. Seabirds are the most abundant and
      widespread avifauna in the Western Indian Ocean and, in this region, oceanic
      islands represent major breeding sites for a large diversity of potential IAV
      host species. Based on serological assays, we assessed the host range of IAV and
      the virus subtype diversity in terns of the islands of the Western Indian Ocean.
      We further investigated the spatial variation in virus transmission patterns
      between islands and identified the origin of circulating viruses using a
      molecular approach. Our findings indicate that terns represent a major host for
      IAV on oceanic islands, not only for seabird-related virus subtypes such as H16,
      but also for those commonly isolated in wild and domestic ducks (H3, H6, H9, H12
      subtypes). We also identified strong species-associated variation in virus
      exposure that may be associated to differences in the ecology and behaviour of
      terns. We discuss the role of tern migrations in the spread of viruses to and
      between oceanic islands, in particular for the H2 and H9 IAV subtypes. 

PMID- 25996399
TI  - Preventive study in subjects at risk of fatal familial insomnia: Innovative
      approach to rare diseases.
AB  - The text describes a preventive clinical trial with drug treatment in a very rare
      neurodegenerative disease (Fatal familial Insomnia, FFI) designed with the help
      of individuals at genetic risk of developing the disease, asymptomatic carriers,
      who have agreed to be exposed over a 10-year period to doxycycline, an antibiotic
      with anti-prion activity. At least 10 carriers of the FFI mutation over 42 y old
      will be treated with doxycycline (100 mg/die) and the incidence of the disease
      will be compared to that of an historical dataset. For ethical reasons a
      randomized, double-blind, placebo-controlled trial was not feasible, however the
      study design and the statistical analysis ensure the scientific value of the
      results. This approach might represent an important breakthrough in terms of
      potential therapy and knowledge of rare diseases that could give some hopes to
      these neglected patients.

PMID- 25996400
TI  - Prion aggregates transfer through tunneling nanotubes in endocytic vesicles.
AB  - Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative
      diseases caused by the misfolding of the cellular prion protein to an infectious
      form PrP(Sc). The intercellular transfer of PrP(Sc) is a question of immediate
      interest as the cell-to-cell movement of the infectious particle causes the
      inexorable propagation of disease. We have previously identified tunneling
      nanotubes (TNTs) as one mechanism by which PrP(Sc) can move between cells. Here
      we investigate further the details of this mechanism and show that PrP(Sc)
      travels within TNTs in endolysosomal vesicles. Additionally we show that prion
      infection of CAD cells increases both the number of TNTs and intercellular
      transfer of membranous vesicles, thereby possibly playing an active role in its
      own intercellular transfer via TNTs. 

PMID- 25996401
TI  - Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease with
      14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean
      Creutzfeldt-Jakob disease active surveillance program.
AB  - Although Korea had a national surveillance system for Creutzfeldt-Jakob disease
      (CJD), it was mainly dependent on attending physician's reports. Thus, little
      prospective data about the epidemiology, characteristics, and final diagnoses of
      suspected patients were available. We have established a nationwide network for
      the active surveillance of patients with suspected CJD. When the requested
      cerebrospinal fluid (CSF) samples tested positive for 14-3-3 protein, we
      investigated the clinical characteristics of the corresponding patients and
      followed them until their final diagnoses were confirmed. A total of 218 samples
      were requested for CSF assays from May 2010 to August 2012, and 106 (48.6%) were
      positive for 14-3-3 protein. In 89 patients with complete clinical data, 38
      (42.7%) were diagnosed with probable CJD and the estimated annual occurrence of
      CJD was 16.3 persons-per-year. The most common diagnoses of the remainder were
      central nervous system infection and any-cause encephalopathy. Non-CJD subjects
      showed worse initial consciousness levels than CJD patients. This preliminary
      study showed that the number of reported cases of CJD and the true positivity
      rates of CSF 14-3-3 protein assays were both low in Korea. An active surveillance
      system is urgently needed to provide the latest nationwide epidemiological data
      of CJD. 

PMID- 25996402
TI  - Embracing open access and offering greater choice for authors.

PMID- 25996404
TI  - Aichi virus 1: environmental occurrence and behavior.
AB  - Aichi virus 1 (AiV-1), belonging to the genus Kobuvirus in the family
      Picornaviridae, has been proposed as a causative agent of human gastroenteritis
      potentially transmitted by fecal-oral routes through contaminated food or water.
      AiV-1 is globally distributed and has been detected in various types of
      environmental samples, such as sewage, river water, groundwater, and shellfish.
      Recent environmental studies revealed that this virus could be detected in higher
      frequency and greater abundance than other human enteric viruses. These findings
      suggest that AiV-1 could potentially be an appropriate indicator of viral
      contamination in the environment because of its high prevalence in water
      environments as well as structural and genetic similarity with some of the other
      important enteric viruses. Further studies on the occurrence and fate of AiV-1 in
      environments, even in combination with clinical studies of many regions, are
      needed for a better understanding of their epidemiology, temporal and
      geographical distribution, environmental stability, and potential health risks to
      humans. 

PMID- 25996405
TI  - Impact of environmental factors on legionella populations in drinking water.
AB  - To examine the impact of environmental factors on Legionella in drinking water
      distribution systems, the growth and survival of Legionella under various
      conditions was studied. When incubated in tap water at 4  degrees C, 25  degrees
      C, and 32  degrees C, L. pneumophila survival trends varied amongst the
      temperatures, with the stable populations maintained for months at 25  degrees C
      and 32  degrees C demonstrating that survival is possible at these temperatures
      for extended periods in oligotrophic conditions. After inoculating coupons of
      PVC, copper, brass, and cast iron, L. pneumophila colonized biofilms formed on
      each within days to a similar extent, with the exception of cast iron, which
      contained 1-log less Legionella after 90 days. L. pneumophila spiked in a model
      drinking water distribution system colonized the system within days. Chlorination
      of the system had a greater effect on biofilm-associated Legionella
      concentrations, with populations returning to pre-chlorination levels within six
      weeks. Biofilms sampled from drinking water meters collected from two areas
      within central Arizona were analyzed via PCR for the presence of Legionella.
      Occurrence in only one area indicates that environmental differences in water
      distribution systems may have an impact on the survival of Legionella. These
      results document the impact of different environmental conditions on the survival
      of Legionella in water. 

PMID- 25996406
TI  - Veneer Ceramic to Y-TZP Bonding: Comparison of Different Surface Treatments.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of various surface
      treatment techniques for enhancing the bond strength between veneering ceramic
      and yttria-stabilized tetragonal zirconia polycrystals (Y-TZP). MATERIALS AND
      METHODS: Pre-sintered Y-TZP specimens were divided into eight groups (n = 10)
      according to the surface-treatment technique used: (a) untreated (control); (b)
      air abrasion with aluminum oxide particles; (c) erbium, chromium:yttrium-scandium
      gallium-garnet (Er,Cr:YSGG) laser irradiation at different energy intensities (1
      to 6 W). All specimens were then sintered and veneered with veneering ceramic
      according to the manufacturer's instructions. The obtained zirconia-ceramic
      specimens were immersed in 37 degrees C distilled water for 24 hours before a
      shear bond strength test using a universal testing device at a 1 mm/min crosshead
      speed. The average values were calculated. After debonding, the Y-TZP surfaces
      were examined under a stereomicroscope to determine their fracture pattern, and
      the surface topography was evaluated with scanning electron microscopy after
      surface treatments. RESULTS: The bond strength ranged from 13.24 to 20.54 MPa.
      All surface treatments increased the bond strength between the veneering ceramic
      and Y-TZP; however, the value for the 6 W irradiation group was significantly
      different from the values for other groups (p ? 0.05). CONCLUSIONS: The present
      study's findings showed that higher energy densities were needed for the laser
      irradiation to improve the bond strength between the veneering ceramic and
      zirconia. CLINICAL IMPLICATION: Y-TZP is commonly used as a core material in
      fixed restorations. The bond strength between zirconia and the veneering ceramic
      can be affected by various surface treatments.

PMID- 25996407
TI  - Quantifying the contributions of base selectivity, proofreading and mismatch
      repair to nuclear DNA replication in Saccharomyces cerevisiae.
AB  - Mismatches generated during eukaryotic nuclear DNA replication are removed by two
      evolutionarily conserved error correction mechanisms acting in series,
      proofreading and mismatch repair (MMR). Defects in both processes are associated
      with increased susceptibility to cancer. To better understand these processes, we
      have quantified base selectivity, proofreading and MMR during nuclear DNA
      replication in Saccharomyces cerevisiae. In the absence of proofreading and MMR,
      the primary leading and lagging strand replicases, polymerase E and polymerase
      delta respectively, synthesize DNA in vivo with somewhat different error rates
      and specificity, and with apparent base selectivity that is more than 100 times
      higher than measured in vitro. Moreover, leading and lagging strand replication
      fidelity rely on a different balance between proofreading and MMR. On average,
      proofreading contributes more to replication fidelity than does MMR, but their
      relative contributions vary from nearly all proofreading of some mismatches to
      mostly MMR of other mismatches. Thus accurate replication of the two DNA strands
      results from a non-uniform and variable balance between error prevention,
      proofreading and MMR. 

PMID- 25996409
TI  - Co-delivery of hydrophobic paclitaxel and hydrophilic AURKA specific siRNA by
      redox-sensitive micelles for effective treatment of breast cancer.
AB  - In this study, a novel redox-sensitive micellar system constructed from a
      hyaluronic acid-based amphiphilic conjugate (HA-ss-(OA-g-bPEI), HSOP) was
      successfully developed for tumor-targeted co-delivery of paclitaxel (PTX) and
      AURKA specific siRNA (si-AURKA). HSOP exhibited excellent loading capacities for
      both PTX and siRNA with adjustable dosing ratios and desirable redox-sensitivity
      independently verified by morphological changes of micelles alongside in vitro
      release of both drugs in different reducing environments. Moreover, flow
      cytometry and confocal microscopy analysis confirmed that HSOP micelles were
      capable of simultaneously delivering PTX and siRNA into MDA-MB-231 breast cancer
      cells via HA-receptor mediated endocytosis followed by rapid transport of cargoes
      into the cytosol. Successful delivery and transport amplified the synergistic
      effects between the drugs while leading to substantially greater antitumor
      efficacy when compared with single drug-loaded micelles and non-sensitive co
      loaded micelles. In vivo investigation demonstrated that HSOP micelles could
      effectively accumulate in tumor sites and possessed the greatest antitumor
      efficacy over non-sensitive co-delivery control and redox-sensitive single-drug
      controls. These findings indicated that redox-sensitive HSOP co-delivery system
      holds great promise for combined drug/gene treatment for targeted cancer therapy.

PMID- 25996408
TI  - Micro-irradiation tools to visualize base excision repair and single-strand break
      repair.
AB  - Microscopy and micro-irradiation imaging techniques have significantly advanced
      our knowledge of DNA damage tolerance and the assembly of DNA repair proteins at
      the sites of damage. While these tools have been extensively applied to the study
      of nucleotide excision repair and double-strand break repair, their application
      to the repair of oxidatively-induced base lesions and single-strand breaks is
      just beginning to yield new insights. This review will focus on examining micro
      irradiation techniques reported to create base lesions and single-strand breaks;
      these lesions are considered to be primarily addressed by proteins involved in
      the base excision repair (BER) pathway. By examining conditions for generating
      these DNA lesions and reviewing information on the assembly and dissociation of
      repair complexes at the induced lesion sites, we hope to promote further
      investigations into BER and to stimulate further development and enhancement of
      these techniques for the study of BER. 

PMID- 25996410
TI  - Epinecidin-1 antimicrobial activity: In vitro membrane lysis and In vivo efficacy
      against Helicobacter pylori infection in a mouse model.
AB  - Helicobacter pylori (H. pylori) infection is highly prevalent, and has a strong
      association with various gastric diseases, including gastritis, digestive ulcers,
      and cancer. H. pylori strains with resistance to existing antibiotics have
      emerged in the past two decades. Currently, treatment of H. pylori infection
      (involving the use of proton pump inhibitors, followed by triple therapy with
      broad-spectrum antibiotics) is suboptimal, with high failure rates. As such,
      there is a clear need for new approaches against H. pylori. Here, we report that
      Epinecidin-1 (Epi-1) shows effective bactericidal activity against H. Pylori in
      vitro, and modulates H. Pylori-induced host immune responses in a mouse model.
      Epi-1 exhibited a low minimum inhibitory concentration (MIC) against antibiotic
      sensitive and clinical antibiotic-resistant strains. Moreover, Epi-1 treatment
      caused 1-N-phenylnaphthylamine (NPN)-fluorescent probe uptake, suggesting it
      induced membrane lysis; transmission electron micrographs revealed that membranes
      were destabilized by the generation of saddle-splay membrane curvature. Oral
      administration of Epi-1 (quaque die dose) in a mouse infection model had strong
      efficacy (p < 0.00152) against H. pylori, as compared with conventional proton
      pump inhibitor (PPI)-triple therapeutic antibiotics. Epi-1 inhibited infection
      through in vivo depletion of CD4+-FOXP3+ T Regulatory and Th17 subset
      populations, and aided in clearance of persistent H. pylori colonization. Flow
      cytometry and gene expression analysis of mouse splenic and gastric tissue
      indicated that Epi-1 inhibits IL-10, and thereby affects FOXP3 expression levels
      and reduces pro-inflammatory cytokine responses. Crucially, high doses of Epi-1
      did not exert toxic effects in oral, dermal, and eye irritation models.
      Collectively, our results suggest that Epi-1 may be a promising, effective, and
      safe monotherapeutic agent for the treatment of multi-drug resistant H. pylori
      infection. 

PMID- 25996411
TI  - Blood-brain barrier-permeable fluorone-labeled dieckols acting as neuronal ER
      stress signaling inhibitors.
AB  - We studied the blood-brain barrier (BBB) permeability and intracellular
      localization of a fluorescein isothiocyanate (FITC)-labeled dieckol (1) and a
      rhodamine B-labeled dieckol (7), for exploring the possible therapeutic
      application of fluorone-labeled dieckols in neurodegenerative diseases. Both
      compounds (1 &7) were synthesized through a click reaction and were found to be
      localized in the endoplasmic reticulum (ER) of the two types of brain cell lines
      (SH-SY5Y and BV-2 cells) tested; they also reduced ER stress in the SH-SY5Y human
      neuroblastoma cells. In addition, 1 and 7 were shown to pass the BBB in rats upon
      intravenous administration. Altogether, our study demonstrates, for the first
      time, that targeted ER-stress reduction in brain cells can be achieved by
      introducing fluorone-dieckol conjugates into systemic circulation. Therefore, 1
      and 7 provide a novel and promising ER-targeting therapeutic strategy for
      neurodegenerative diseases. 

PMID- 25996412
TI  - Optimization of intrinsic and extrinsic tendon healing through controllable water
      soluble mitomycin-C release from electrospun fibers by mediating adhesion-related
      gene expression.
AB  - To balance intrinsic and extrinsic healing during tendon repair is challenging in
      tendon surgery. We hypothesized that by mediating apoptotic gene and collagen
      synthesis of exogenous fibroblasts, the adhesion formation induced by extrinsic
      healing could be inhibited. With the maintenance of intrinsic healing, the tendon
      could be healed with proper function with no adhesion. In this study, we loaded
      hydrophilic mitomycin-C (MMC) into hyaluronan (HA) hydrosols, which were then
      encapsulated in poly(L-lactic acid) (PLLA) fibers by micro-sol electrospinning.
      This strategy successfully provided a controlled release of MMC to inhibit
      adhesion formations with no detrimental effect on intrinsic healing. We found
      that micro-sol electrospinning was an effective and facile approach to
      incorporate and control hydrophilic drug release from hydrophobic polyester
      fibers. MMC exhibited an initially rapid, and gradually steadier release during
      40 days, and the release rates could be tuned by its concentration. In vitro
      studies revealed that low concentrations of MMC could inhibit fibroblast adhesion
      and proliferation. When lacerate tendons were healed using the MMC-HA loaded PLLA
      fibers in vivo, they exhibited comparable mechanical strength to the naturally
      healed tendons but with no significant presence of adhesion formation. We further
      identified the up-regulation of apoptotic protein Bax expression and down
      regulation of proteins Bcl2, collage I, collagen III and alpha-SMA during the
      healing process associated with minimum adhesion formations. This approach
      presented here leverages new advances in drug delivery and nanotechnology and
      offers a promising strategy to balance intrinsic and extrinsic tendon healing
      through modulating genes associated with fibroblast apoptosis and collagen
      synthesis. 

PMID- 25996413
TI  - Changes in the diagnosis and treatment of achalasia.

PMID- 25996414
TI  - Breastfeeding and Risk of Breast Cancer: Case-Control Study.
AB  - The aim of this study was to investigate a possible association of breast cancer
      occurrence in women with their breastfeeding experience. A matched case-control
      study was conducted in Kragujevac, Serbia. A total of 382 women (191 cases with
      breast cancer and 191 controls) were interviewed, but the data were explored on
      breastfeeding and breast cancer only among parous women (339 women). Logistic
      regression was used to calculate odds ratios (ORs) as estimates of the relative
      risk of breast cancer. Compared with controls, significantly more cases ever
      breastfed [adjusted OR (ORadj) = 2.90, 95 percent confidence interval (95 percent
      CI) 1.02-8.22], breastfed all their children (ORadj = 2.93; 95 percent CI 1.03
      8.29), and had longer lifetime duration of breastfeeding (ORadj = 3.44, 95
      percent CI 1.15-10.24 for 13 or more months). In comparison with controls,
      significantly more cases breastfed at first birth (ORadj = 3.17, 95 percent CI
      1.36-7.37). Breast cancer risk increased if first breastfeeding occurred at an
      older age (p for trend = .042) and with longer duration of breastfeeding (p for
      trend = .037). Our study is one of the few in which breastfeeding was found to be
      a risk factor for breast cancer. 

PMID- 25996415
TI  - A quantitative study of MC3T3-E1 cell adhesion, morphology and biomechanics on
      chitosan-collagen blend films at single cell level.
AB  - The interaction between cells and biomaterials plays a key role in cell
      proliferation and differentiation in tissue engineering. However, a quantitative
      analysis of those interactions has been less well studied. The objective of this
      study was to quantitative recapitulate the difference of MC3T3-E1 cell adhesion,
      morphological and biomechanical properties on chitosan-collagen films in terms of
      chemical composition. Here, the unbinding force between MC3T3-E1 cell and a
      series of chitosan-collagen films was probed by a real-time and in situ atomic
      force microscopy-single cell force spectroscopy (AFM-SCFS). Meanwhile, changes in
      cell morphology and Young's modulus on different chitosan-collagen films were
      detected by AFM. The cell area and CCK-8 results showed that cell spreading and
      proliferation increased with increasing collagen content. AFM observations
      clearly showed cell height decreased and pseudopod fusion with the collagen
      content increased. Cell adhesive force increased from 0.76+/-0.17 nN to 1.70+/
      0.19 nN. On the contrary, cells Young's modulus, which reflected biophysical
      changes of cells decreased from 11.94+/-3.19 kPa to 1.81+/-0.52 kPa,
      respectively. It suggested that stronger cell-substrate interactions benefit cell
      adhesion, and better cell flexibility improve cell spreading. The findings
      indicate that cell morphology, adhesive force and Young's modulus are significant
      affected by various chitosan-collagen substrates. Those methods and quantitative
      results have guiding significance for investigating the mechanism of chitosan
      and/or collagen based cell-targeting drug carrier and the preparation of chitosan
      collagen composite biomaterials.

PMID- 25996416
TI  - Diffuse Epithelial Downgrowth Associated With an Extruded Anterior Chamber
      Intraocular Lens Haptic.
AB  - BACKGROUND: Anterior chamber intraocular lenses (ACIOL) have been known to be
      associated with several complications, including endophthalmitis. We present a
      patient who developed another type of severe complication: epithelial downgrowth
      associated with an extruded footplate of an ACIOL. METHODS: Case report. RESULTS:
      A 70-year-old schizophrenic woman underwent implantation of an ACIOL during
      cataract extraction that was complicated by posterior capsular rupture, erratic
      patient movement, conversion to extracapsular cataract extraction (ECCE), and
      vitreous loss in her left eye. She subsequently presented with progressively
      decreasing vision, and she was found to have extensive epithelial downgrowth that
      also resulted in neovascularization of the iris and recurrent hyphemas. The
      patient elected to have the ACIOL explanted, and at the time of the surgery, it
      was noted that one of the footplates of the ACIOL was protruding through the
      original ECCE wound. We believe that the extrusion of this footplate was one
      contributing factor toward severe epithelial downgrowth. CONCLUSIONS: Although
      exposure of an ACIOL haptic is a very rare occurrence, it can have severe
      consequences, including epithelial downgrowth.

PMID- 25996417
TI  - Use of Wavefront Imaging Technology to Demonstrate Improvement in Corneal
      Aberrations Using Piggyback Contact Lens in a Keratoconus Eye With Intrastromal
      Corneal Ring Segment Implantation: A Case Report.
AB  - OBJECTIVE: To quantify short-term changes in corneal high-order aberrations (HOA)
      with piggyback contact lens use in an eye with keratoconus that had undergone
      intrastromal ring segment (Intacs) implantation. METHODS: A patient with
      keratoconus reporting of distorted images after Intacs surgery was found to have
      HOA (trefoil, point spread function [PSF], and modulation transfer function
      [MTF]) as measured using wavefront technology (Nidek OPD-Scan III) and evidenced
      by her cylindrical correction. She underwent piggyback contact lens (silicone
      hydrogel and fluoroperm rigid gas-permeable lenses) fitting in an attempt to
      improve the HOA. RESULTS: After piggyback contact lens fitting, her visual acuity
      improved and all her visual symptoms resolved. High-order aberrations reduced
      from 3.152 to 0.490 after the lens fitting and was noted to be 0.447 at 6 months;
      trefoil also significantly improved (0.360-0.096; it was 0.031 at 6 months). The
      cylinder decreased from -4.50 to -0.75 and was stable at 6 months (-1.00). There
      was also significant improvement in PSF and MTF. CONCLUSIONS: Visual acuity and
      symptoms along with HOA and cylinder improved after fitting of piggyback contact
      lens in our patient with keratoconus who had undergone Intacs.

PMID- 25996418
TI  - In Response: Changes in Ultraviolet Transmittance of Hydrogel and Silicone
      Hydrogel Contact Lenses Induced by Wear.

PMID- 25996419
TI  - Evaluation of Effect of Topical Tacrolimus Treatment on Herpetic Stromal
      Keratitis in a Rat Model.
AB  - OBJECTIVES: To investigate the effectiveness of topical tacrolimus treatment on
      herpetic stromal keratitis (HSK) in a rat model. METHODS: The development of HSK
      was monitored for 14 days after the inoculation of rats with herpes simplex type
      1 virus. Rats that developed HSK were divided into four groups as follows: (1)
      topical antiviral treatment (control), (2) topical antiviral and 1% prednisolone
      acetate, (3) topical antiviral and 0.03% tacrolimus ointment, and (4) topical
      antiviral plus 0.1% tacrolimus ointment. After 14 days of treatment, the severity
      levels of HSK were scored and compared with the levels before the treatment. The
      expression of CD3, CD4, and CD8 was evaluated by flow cytometry. The development
      of the disease was evaluated clinically and histologically. RESULTS: Significant
      improvement in vascularization was observed in the groups with the drug treatment
      in addition to the antiviral agent (P<0.05), but there was no obvious difference
      within groups 2, 3, and 4 in the vascularization severity. The regression of
      corneal edema was 8.05%+/-6% in group 1, 25.17%+/-14.55% in group 2 (P=0.01),
      36.40%+/-21.69% in group 3 (P=0.03), and 46.39%+/-14.96% in group 4 (P=0.00). A
      significant decrease in the number of inflammatory cells in the groups with the
      drug treatment was evaluated by immunohistochemical staining and confirmed by
      flow cytometry analysis. CONCLUSIONS: Topical tacrolimus treatment caused a
      significant decrease in corneal vascularization accompanied by a lower number of
      inflammatory cells in the experimental HSK corneal edema model. Therefore,
      topical tacrolimus has the potential to be used in the treatment of HSK.

PMID- 25996420
TI  - Improvement of Subjective Symptoms and Eye Complications When Changing From 2
      Week Frequent Replacement to Daily Disposable Contact Lenses in a Subscriber
      Membership System.
AB  - PURPOSE: Subjective symptoms and other eye complications were assessed and
      retrospectively compared in patients belonging to a proprietary membership system
      who switched from 2-week frequent replacement (2WFR) wear to daily disposable
      (DD) lens use. METHODS: Questionnaire responses were completed by all patients
      for a 5-year interval between October 2008 and September 2013 from 83 wearers in
      three Japanese clinics (59 female and 24 male; average age: 33.4+/-10.9 years).
      Complications were recorded for each patient at times of reexamination. RESULTS:
      Over the 5-year observation period, the 83 patients wore lenses for more than 26
      months. The average duration of use of 2WFR lenses was 14.5+/-2.7 days/lens
      (n=83) and subsequently 1.03+/-0.12 days/lens (n=83) for DD lenses. Compliance
      with the duration of use was consistently good as monitored by requests for lens
      resupply in both wearing modalities. The subjective complaint of dryness tended
      to consistently show improvement by the change to DD wear: 18.1% vs. 30.1%
      (P=0.10, Fisher exact test). Among eye complications noted in each group, the
      occurrence of superficial punctate keratitis (SPK) was significantly decreased in
      DD wear: 9.6% vs. 26.5% (P=0.008, Fisher exact test). The main reasons given by
      patients for changing to DD wear were (1) "DD lens wear was more hygienic"
      (78.6%) and (2) "DD lens use is more convenient for travel/business trips"
      (64.3%). Comments after the switch in wear were (1) "easy and convenient" (95.7%)
      and (2) "I don't have to worry about expiration dates" on solutions (57.1%).
      Overall, 95.7% of wearers making the change answered as "satisfied" and "mostly
      satisfied." CONCLUSIONS: In the subscription membership program, which provided
      free lens replacement and/or reexamination, individual compliance with duration
      of wear in 2WFR wear cycles was good; however, these patients switching to DD
      wear tended to have improvement in their subjective complaints of dryness and
      objectively demonstrated a significant reduction of SPK at follow-up
      examinations.

PMID- 25996421
TI  - Intraoperative Suprachoroidal Hemorrhage After Penetrating Keratoplasty: Case
      Series and Review of Literature.
AB  - OBJECTIVE: To describe four cases of intraoperative suprachoroidal hemorrhage
      (SCH) during penetrating keratoplasty and to review the literature. METHODS:
      Cases with intraoperative SCH during penetrating keratoplasty over 3-year period
      were reviewed. The parameters evaluated were ocular and systemic risk factors,
      intraoperative details, and postoperative outcomes. A review of literature of
      intraoperative SCH during penetrating keratoplasty was also conducted. RESULTS:
      Of the 543 cases that underwent penetrating keratoplasty for optical indications
      during the study period, four cases developed intraoperative SCH, which is an
      incidence of 0.73%. Suprachoroidal hemorrhage occurred in the following cases:
      failed pediatric graft, donor eye in a case of contralateral autokeratoplasty,
      Marfan syndrome with aphakic bullous keratopathy who had undergone multiple
      ocular surgeries, and a case of healed keratitis with corneoiridic scar. The mean
      age, axial length, and intraocular pressure were 32.75+/-22.17 years (range, 4-57
      years), 23.29+/-2.12 mm (range, 20.38-25.2 mm), and 16.25+/-3.86 mm Hg (range, 16
      20 mm Hg), respectively. Postoperatively, two eyes had a best-corrected visual
      acuity (BCVA) of counting fingers. The third case had BCVA of light perception
      (LP), and fourth eye had no LP. CONCLUSION: The visual outcomes in cases of open
      sky penetrating keratoplasty with SCH continue to be abysmally poor. The
      importance of thoroughly informing the patient about this complication cannot be
      underrated.

PMID- 25996422
TI  - Descemet Stripping Automated Endothelial Keratoplasty for Endothelial Dysfunction
      in Xeroderma Pigmentosum: A Clinicopathological Correlation and Review of
      Literature.
AB  - Xeroderma pigmentosum (XP) mainly affects the ocular surface; however,
      endothelial damage may also occur. We would like to report changes in the
      endothelial-Descemet layer and review the literature on similar findings in
      patients with XP, including the role of Descemet stripping automated endothelial
      keratoplasty (DSAEK) in the management of a 21-year-old man who presented with
      nonresolving corneal edema in the right eye after excision biopsy for
      conjunctival intraepithelial neoplasia. His best-corrected visual acuity (BCVA)
      was 20/200 in the right eye and 20/20 in the left eye. On general examination,
      there was patchy hyperpigmentation of the exposed areas of skin suggestive of XP.
      On examination of the right eye, there was stromal edema involving the exposed
      half of cornea. The left eye appeared normal. Pachymetry readings were 860 and
      600 MUm in the right and left eye, respectively. Descemet stripping automated
      endothelial keratoplasty was performed for endothelial dysfunction and the
      stripped endothelium, and Descemet membrane (DM) was sent for histopathologic
      evaluation. Postoperatively, the donor lenticule was well apposed and the
      overlying stromal edema resolved. The patient achieved a BCVA of 20/30 in the
      right eye without progression of corneal scarring at 1-year follow-up. In the
      meanwhile, however, the left eye developed corneal edema. Histopathology revealed
      gross attenuation of endothelial cells with uniform thickness of the DM. Corneal
      endothelial dysfunction in XP is amenable to treatment with DSAEK. 

PMID- 25996423
TI  - Cross-Linking and Intracorneal Ring Segments--Review of the Literature.

PMID- 25996424
TI  - (How) observed eye-contact modulates gaze following. An fMRI study.
AB  - Humans are highly sensitive to directional gaze cues and rapidly shift attention
      in accordance with others' gaze (i.e., gaze following). Besides providing
      information about the physical environment, for instance, the location of an
      object, gaze direction can be used to extract information about the social
      environment, such as whether or not two people are interacting with each other.
      In the present fMRI study we investigated how these two different types of
      information conveyed by gaze direction interact with one another. Participants
      saw two faces that were either looking at each other or away from each other
      before jointly shifting gaze toward one of two target locations. Targets either
      appeared at the gazed at or the non-gazed at location. Behaviorally, gaze
      following (faster responses to congruent versus incongruent trials) was more
      prominent after observing eye contact than after observing no eye contact. In
      line with behavioral findings, neuroimaging results revealed enhanced activation
      in fronto-parietal and temporal areas in congruent trials when faces had looked
      at each other versus away from each other. These findings demonstrate that
      observing an attentional relation between others augments processing of their
      subsequent gaze cues.

PMID- 25996425
TI  - COMPARING THE OUTCOME OF SINGLE VERSUS MULTIPLE SESSION LASER PHOTOABLATION OF
      FLAT NEOVASCULARIZATION IN ZONE 1 AGGRESSIVE POSTERIOR RETINOPATHY OF
      PREMATURITY: A Prospective Randomized Study.
AB  - PURPOSE: To compare single versus 2-session laser photoablation for flat
      neovascularization in cases with Zone 1 aggressive posterior retinopathy of
      prematurity. METHODS: Twenty-nine Asian Indian infants with aggressive posterior
      retinopathy of prematurity were randomized; each eye received 1 of 2 methods (29
      each in Group A or B) proposed by the PHOTO-ROP group. Group A underwent single
      session laser to the avascular retina underlying the flat neovascularization by
      direct laser over the fronds. Group B underwent laser in 2 sessions; first, laser
      was delivered to the avascular periphery up to the flat neovascularization and 7
      days later to the avascular bed exposed by the retraction of the fronds. Outcome
      and complications between the two groups were compared. RESULTS: Mean birthweight
      and gestational ages were 1,276 g and 30.1 weeks, respectively. All eyes showed
      favorable outcome at a minimum 12-month follow-up. Hemorrhages after laser (41.4%
      vs. 17.2%, P < 0.001) were more common in the single laser group. Large
      hemorrhages (>1 disk diameter) seen in Group A took longer than 8 weeks to
      resolve and developed focal fibrosis. CONCLUSION: This study demonstrates that
      the two-staged laser procedure produces fewer and smaller hemorrhages and no
      fibrosis compared with a single session. Both methods have comparable favorable
      outcomes in Asian Indian infants.

PMID- 25996426
TI  - EFFECT OF SYSTEMIC BETA-BLOCKERS, ACE INHIBITORS, AND ANGIOTENSIN RECEPTOR
      BLOCKERS ON DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH AGE
      RELATED MACULAR DEGENERATION.
AB  - PURPOSE: Recent studies have suggested that the use of systemic beta-blockers,
      angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can
      induce regression of choroidal neovascularization in rodent models. The purpose
      of this study is to evaluate if these agents have a protective effect against the
      development of choroidal neovascularization in patients with age-related macular
      degeneration. METHODS: In this single-center retrospective case-control study,
      the charts of 250 patients with neovascular age-related macular degeneration were
      compared with those of 250 controls with dry age-related macular degeneration.
      Charts were reviewed for current and past use of beta-blockers, angiotensin
      converting enzyme inhibitors, and angiotensin receptor blockers. Frequency tables
      were generated, and associations were examined using chi-square tests, t-tests,
      and multivariate logistic regression. RESULTS: There was no statistically
      significant difference between rates of beta-blocker use (P = 0.57), angiotensin
      converting enzyme inhibitors use (P = 0.20), or angiotensin receptor blockers use
      (P = 0.61) between the 2 groups. Additionally, there was no statistically
      significant difference between rates of use of combinations of the above drugs
      between the two groups. CONCLUSION: Although there is growing evidence that beta
      blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor
      blockers can induce regression of choroidal neovascularization in rodent models,
      these medications do not seem to confer a protective effect against the
      development of choroidal neovascularization in patients with age-related macular
      degeneration.

PMID- 25996427
TI  - INTRAVITREAL BEVACIZUMAB IN THE TREATMENT OF CHOROIDAL NEOVASCULAR MEMBRANE DUE
      TO ANGIOID STREAKS.
AB  - PURPOSE: To investigate the results of intravitreal bevacizumab for choroidal
      neovascularization (CNV) secondary to angioid streaks and to assess the factors
      influencing disease progression. METHODS: Patients treated with intravitreal
      bevacizumab (1.25 mg/0.05 mL) for CNV secondary to angioid streaks were reviewed
      retrospectively. In addition to demographic findings, ophthalmologic findings at
      baseline and during follow-ups were recorded. RESULTS: Twenty-three eyes of 20
      patients (mean age, 45.7 years; 7 women) were included in the study. Mean follow
      up was 23 months. Mean number of injections was 5.1. Initial and final logMAR
      visual acuity was not different (0.53 +/- 0.33 and 0.60 +/- 0.40 logMAR, P =
      0.79). At the last examination, patients with final active CNV (N = 14) were
      younger (mean age, 42 years) than patients with final inactive CNV (N = 9) (mean
      age, 52 years). The former group required higher number of injections (6.6 vs.
      2.8, P = 0.013). Eyes with pseudoxanthoma elasticum (N = 10) needed injections
      every 4.4 months while the others (N = 13) every 7.2 months (P = 0.072).
      Pseudoxanthoma elasticum positivity ended up with active membranes in 70% of the
      cases, composing half of the overall final active CNVs in this study. CONCLUSION:
      Intravitreal bevacizumab stabilized vision in eyes with CNV and angioid streaks.
      At younger ages, CNV behaved more aggressively and seemed to be more resistant to
      treatment.

PMID- 25996428
TI  - Acute ocriplasmin retinopathy.

PMID- 25996429
TI  - ASSOCIATIONS BETWEEN AGE-RELATED MACULAR DEGENERATION, OSTEOARTHRITIS AND
      RHEUMATOID ARTHRITIS: RECORD LINKAGE STUDY.
AB  - PURPOSE: The epidemiologic relationship between age-related macular degeneration
      (AMD) and arthritis is unknown and has implications for understanding disease
      pathogenesis and treatment strategies. METHODS: An AMD cohort of 245,912 people
      was constructed from English linked hospital episode statistics (1999-2011),
      principally comprising neovascular AMD patients undergoing anti-vascular
      endothelial growth factor therapy. We compared the AMD cohort with a reference
      cohort (2,134,771 people) for rates of subsequent osteoarthritis (OA) and
      rheumatoid arthritis. Osteoarthritis (2,032,472 people) and rheumatoid arthritis
      (261,232 people) cohorts were also constructed and compared with the reference
      cohort for rates of subsequent AMD. RESULTS: Risk of arthritis after AMD was not
      elevated. The rate ratio for OA was 0.96 (95% confidence interval 0.95-0.97) and
      for rheumatoid arthritis was 0.98 (0.94-1.02). However, risk of AMD after
      arthritis was modestly raised. For OA, the rate ratio was 1.06 (1.04-1.08), but
      risk increased with longer OA duration, for example, 1.15 (1.08-1.23) for >10
      years. For rheumatoid arthritis, the rate ratio was also modestly elevated at
      1.15 (1.12-1.19). CONCLUSION: Age-related macular degeneration and arthritis are
      degenerative aging conditions that share some disease mechanisms and
      extracellular matrix involvement. However, considering arthritis after AMD, they
      are not positively associated. By contrast, people with OA experience modestly
      increased AMD risk, perhaps owing to medical treatments for OA.

PMID- 25996430
TI  - Patient, victim, or survivor: does language matter? A conversation with Claudia
      Bayliff.

PMID- 25996431
TI  - Risk factors for domestic minor sex trafficking in the United States: a
      literature review.
AB  - BACKGROUND: Domestic minor sex trafficking (DMST) is an important social and
      public health problem, but it has received little attention from healthcare
      professionals in research, practice, and policy. Prevention and early victim
      identification efforts for this population are severely limited or entirely
      absent. PURPOSE: The aim of this study was to integrate evidence on risk factors
      for DMST and critically appraise the quality and quantity of nursing literature
      on DMST. METHODS: This literature review was reported using PRISMA criteria.
      Three databases (CINAHL, PsychInfo, and PubMed) were searched using various terms
      for (a) human trafficking, (b) risk factors, and (c) children. DISCUSSION:
      Demographic factors were not important predictors of DMST. Childhood maltreatment
      trauma and running away from home were the most important risk factors for
      trafficking victimization. There was little nursing literature on the topic of
      DMST. CONCLUSION: Nurses and other healthcare professionals must engage in
      confronting DMST by improving early identification of victims and conducting high
      quality research to inform practice.

PMID- 25996432
TI  - House to house, shelter to shelter: experiences of black women seeking housing
      after leaving abusive relationships.
AB  - Locating safe and affordable housing is a vital step for women who decide to
      leave their abuser. Without housing, many women, particularly those who live in
      poverty, are forced to remain in abusive relationships, accept inadequate or
      unsafe housing, or become homeless (Menard, 2001; Moses, 2010). Women who choose
      to leave their abusers are faced with multiple barriers in establishing their
      independence such as limited financial resources, mental illness, and the lack of
      affordable housing (Botein & Hetling, 2010), putting them at risk of
      revictimization. This pilot study explores the narratives of Black mothers
      currently residing at an emergency intimate partner violence shelter to discover
      their experiences in seeking housing after leaving abusive relationships with a
      focus on housing instability and mental health. Utilizing a qualitative
      descriptive design, four major themes emerged: (a) unstable/insecure housing over
      time, (b) limited support, 

PMID- 25996433
TI  - Beyond urban places: responding to intimate partner violence in rural and remote
      areas.
AB  - Intimate partner violence is a recognized public health problem impacting the
      lives of women, families, and communities. Women in rural and more remote areas
      who experience IPV face unique barriers and challenges to accessing healthcare
      services to support healthy outcomes. Resources, access to services, presence of
      compassionate and informed healthcare providers, and environmental circumstances
      influence effective responses to this issue in rural and more remote areas. In a
      public health approach to this problem, prevention efforts, victim-centered
      responses, and the support of safety are imperative to improve outcomes for
      women. Forensic nurses play an important role in effective response by building
      linkages across health, human, and social systems through collaboration,
      partnership, activism, advocacy, and sensitivity to the issue across the rural
      landscape. 

PMID- 25996434
TI  - Addressing methodological issues in correctional health research: a case report.
AB  - This case study describes the experiences of a novice correctional nurse
      researcher's application of the recommended strategies from the correctional
      literature to improve the conduct of research in a correctional institution. An
      innovative booster intervention was implemented and evaluated as a pilot study in
      a state correctional institution. Correctional nurse researchers encounter many
      challenges when conducting research in a correctional facility. This case study
      shares challenges that persisted and concludes by recommending ways to strengthen
      and improve on learned strategies proposed by experienced correctional nurse
      researchers. 

PMID- 25996437
TI  - Quantification of long anterior lens zonules and their resulting zonule-free zone
      sizes.

PMID- 25996438
TI  - The Effect of Seasonal Thermal Stress on Lipid Mobilisation, Antioxidant Status
      and Reproductive Performance in Dairy Cows.
AB  - Heat stress is a major factor contributing to low fertility of dairy cows with a
      great economic impact in dairy industry. Heat-stressed dairy cows usually have
      reduced nutrient intake, resulting in a higher degree of negative energy balance
      (NEB). The aim of this study was to investigate the seasonal thermal effect on
      lipid metabolism, antioxidant activity and reproductive performance in dairy
      cows. Thirty-two healthy dairy heifers were included in the study. According to
      the ambient temperature, animals were divided into two groups: winter (N = 14)
      and summer season (N = 18). Metabolic parameters, paraoxonase-1 (PON1) activity
      and total antioxidant status (TAS) were monitored at the time of insemination
      (basal values) and from 1 week before until 8 weeks after calving. Number of
      services per conception and calving-to-conception (CC) interval were calculated
      from the farm recording data. Serum triglyceride, non-esterified fatty acids
      (NEFA) and beta-hydroxybutyrate (BHB) concentrations were significantly increased
      after calving in summer compared to winter, indicating higher degree of NEB in
      cows during summer. PON1 activity was significantly decreased after calving in
      both summer and winter group. TAS concentration was significantly lower in summer
      than that in winter. A significantly higher number of services were needed for
      conception in summer compared to winter, and CC interval was significantly longer
      in summer than that in winter as well. Additionally, reproductive performance
      significantly correlated with the severity of NEB, suggesting that lipid
      mobilization and lower antioxidant status contributed to poor reproduction
      ability in dairy cows during hot months. 

PMID- 25996439
TI  - A method to determine the duration of the eclipse phase for in vitro infection
      with a highly pathogenic SHIV strain.
AB  - The time elapsed between successful cell infection and the start of virus
      production is called the eclipse phase. Its duration is specific to each virus
      strain and, along with an effective virus production rate, plays a key role in
      infection kinetics. How the eclipse phase varies amongst cells infected with the
      same virus strain and therefore how best to mathematically represent its duration
      is not clear. Most mathematical models either neglect this phase or assume it is
      exponentially distributed, such that at least some if not all cells can produce
      virus immediately upon infection. Biologically, this is unrealistic (one must
      allow for the translation, transcription, export, etc. to take place), but could
      be appropriate if the duration of the eclipse phase is negligible on the time
      scale of the infection. If it is not, however, ignoring this delay affects the
      accuracy of the mathematical model, its parameter estimates, and predictions.
      Here, we introduce a new approach, consisting in a carefully designed experiment
      and simple analytical expressions, to determine the duration and distribution of
      the eclipse phase in vitro. We find that the eclipse phase of SHIV-KS661 lasts on
      average one day and is consistent with an Erlang distribution. 

PMID- 25996441
TI  - Raman spectroscopy as a diagnostic tool for monitoring acute nephritis.
AB  - Both acute nephritis and chronic nephritis account for substantial morbidity and
      mortality worldwide, partly due to the lack of reliable tools for detecting
      disease early and monitoring its progression non-invasively. In this work, Raman
      spectroscopy coupled with multivariate analysis are employed for the first time
      to study the accelerated progression of nephritis in anti-GBM mouse model.
      Preliminary results show up to 98% discriminant accuracy for the severe and midly
      diseased and the healthy among two strains of mice with different susceptibility
      to acute glomerulonephritis. This technique has the potential for non-invasive or
      minimally-invasive early diagnosis, prognosis, and monitoring of renal disease
      progression. 

PMID- 25996440
TI  - New high affinity monoclonal antibodies recognize non-overlapping epitopes on
      mesothelin for monitoring and treating mesothelioma.
AB  - Mesothelin is an emerging cell surface target in mesothelioma and other solid
      tumors. Most antibody drug candidates recognize highly immunogenic Region I (296
      390) on mesothelin. Here, we report a group of high-affinity non-Region I rabbit
      monoclonal antibodies. These antibodies do not compete for mesothelin binding
      with the immunotoxin SS1P that binds Region I of mesothelin. One pair of
      antibodies (YP218 and YP223) is suitable to detect soluble mesothelin in a
      sandwich ELISA with high sensitivity. The new assay can also be used to measure
      serum mesothelin concentration in mesothelioma patients, indicating its potential
      use for monitoring patients treated with current antibody therapies targeting
      Region I. The antibodies are highly specific and sensitive in immunostaining of
      mesothelioma. To explore their use in tumor therapy, we have generated the
      immunotoxins based on the Fv of these antibodies. One immunotoxin (YP218 Fv-PE38)
      exhibits potent anti-tumor cytotoxicity towards primary mesothelioma cell lines
      in vitro and an NCI-H226 xenograft tumor in mice. Furthermore, we have engineered
      a humanized YP218 Fv that retains full binding affinity for mesothelin-expressing
      cancer cells. In conclusion, with their unique binding properties, these
      antibodies may be promising candidates for monitoring and treating mesothelioma
      and other mesothelin-expressing cancers. 

PMID- 25996442
TI  - Synthesis of Fullerene-Fused Dioxanes/Dioxepanes: Ferric Perchlorate-Mediated One
      Step Reaction of [60]Fullerene with Diols.
AB  - The facile one-step reaction of [60]fullerene with various diols in the presence
      of ferric perchlorate afforded a series of rare fullerene-fused
      dioxanes/dioxepanes. Nevertheless, the reaction of [60]fullerene with diethylene
      glycol, triethylene glycol, and tripropylene glycol promoted by ferric
      perchlorate unexpectedly generated fullerene-fused dioxanes instead of the
      anticipated fullerene-fused crown ethers. A plausible reaction mechanism is
      proposed to explain the formation of fullerene-fused dioxane/dioxepane products. 

PMID- 25996443
TI  - Accelerated motion corrected three-dimensional abdominal MRI using total
      variation regularized SENSE reconstruction.
AB  - PURPOSE: Develop a nonrigid motion corrected reconstruction for highly
      accelerated free-breathing three-dimensional (3D) abdominal images without
      external sensors or additional scans. METHODS: The proposed method accelerates
      the acquisition by undersampling and performs motion correction directly in the
      reconstruction using a general matrix description of the acquisition. Data are
      acquired using a self-gated 3D golden radial phase encoding trajectory, enabling
      a two stage reconstruction to estimate and then correct motion of the same data.
      In the first stage total variation regularized iterative SENSE is used to
      reconstruct highly undersampled respiratory resolved images. A nonrigid
      registration of these images is performed to estimate the complex motion in the
      abdomen. In the second stage, the estimated motion fields are incorporated in a
      general matrix reconstruction, which uses total variation regularization and
      incorporates k-space data from multiple respiratory positions. The proposed
      approach was tested on nine healthy volunteers and compared against a standard
      gated reconstruction using measures of liver sharpness, gradient entropy, visual
      assessment of image sharpness and overall image quality by two experts. RESULTS:
      The proposed method achieves similar quality to the gated reconstruction with
      nonsignificant differences for liver sharpness (1.18 and 1.00, respectively),
      gradient entropy (1.00 and 1.00), visual score of image sharpness (2.22 and
      2.44), and visual rank of image quality (3.33 and 3.39). An average reduction of
      the acquisition time from 102 s to 39 s could be achieved with the proposed
      method. CONCLUSION: In vivo results demonstrate the feasibility of the proposed
      method showing similar image quality to the standard gated reconstruction while
      using data corresponding to a significantly reduced acquisition time. Magnetic
      Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance.

PMID- 25996444
TI  - Consecutive Cycloaddition/S(N)Ar/Reduction/Cyclization/Oxidation Sequences: A
      Copper-Catalyzed Multicomponent Synthesis of Fused N-Heterocycles.
AB  - A highly efficient multicomponent domino protocol has been developed for the
      synthesis of 5-phenyl-[1,2,3]triazolo[1,5-c]quinazolines from simple and readily
      available (E)-1-bromo-2-(2-nitrovinyl)benzenes, aldehydes, and sodium azide. This
      elegant domino process involved consecutive [3 + 2] cycloaddition, copper
      catalyzed S(N)Ar, reduction, cyclization, and oxidation sequences. Notably,
      sodium azide acted as a dual nitrogen source in the construction of this novel
      fused N-heterocycle.

PMID- 25996445
TI  - Evaluation of separation properties of a modified strong cation exchange material
      named MEX and its application in 2D-MEX * C18 system to separate peptides from
      scorpion venom.
AB  - Peptides from scorpion venom represent one of the most promising drug sources for
      drug discovery for some specific diseases. Current challenges in their separation
      include high complexity, high homologies and the huge range of peptides. In this
      paper, a modified strong cation exchange material, named MEX, was utilised for
      the two-dimensional separation of peptides from complex scorpion venom. The
      silica-based MEX column was bonded with two functional groups; benzenesulfonic
      acid and cyanopropyl. To better understand its separation mechanisms, seven
      standard peptides with different properties were employed in an evaluation study,
      the results of which showed that two interactions were involved in the MEX
      column: electrostatic interactions based on benzenesulfonic acid groups dominated
      the separation of peptides; weak hydrophobic interactions introduced by
      cyanopropyl groups increased the column's selectivity for peptides with the same
      charge. This characteristic allowed the MEX column to overcome some of the
      drawbacks of traditional strong cation exchange (SCX) columns. Furthermore, the
      study showed the great effects of the acetonitrile (ACN) content, the sodium
      perchlorate (NaClO4) concentration and the buffer pH in the mobile phase on the
      peptides' retention and separation selectivity on the MEX column. Subsequently,
      the MEX column was combined with a C18 column to establish an off-line 2D-MEX *
      C18 system to separate peptides from scorpion Buthus martensi Karsch (BmK) venom.
      Due to complementary separation mechanisms in each dimension, a high
      orthogonality of 47.62% was achieved. Moreover, a good loading capacity,
      excellent stability and repeatability were exhibited by the MEX column, which are
      beneficial for its use in future preparation experiments. Therefore, the MEX
      column could be an alternative to the traditional SCX columns for the separation
      of peptides from scorpion venom. 

PMID- 25996446
TI  - A macrocyclic tetraamine bearing four phenol groups: a new class of heptadentate
      ligands to provide an oxygen-sensitive luminescent Tb(III) complex with an
      extendable phenol pendant arm.
AB  - This paper presents a 1,4,7,10-teraazacyclododecane-based tetrakis-phenol as a
      protonated ligand precursor and its oxygen-sensitive luminescent terbium(III)
      complex with an extendable phenol pendant arm (Phi = 0.91 under N2, Phi = 0.031
      under air), in which the potentially N4O4-octadentate ligand unprecedentedly
      coordinates to the Tb(3+) ion in a N4O3-heptadentate fashion.

PMID- 25996447
TI  - Stereoselective Polymerization of rac-Lactide Catalyzed by Zinc Complexes with
      Tetradentate Aminophenolate Ligands in Different Coordination Patterns: Kinetics
      and Mechanism.
AB  - A series of monomeric zinc silylamido complexes bearing [NNNO]-type tetradentate
      aminophenolate ligands, LZnN(SiMe3)2 [L = {(2-R(1))ArCH2N[(CH2)2R(2)]CH2(4-R(4)-6
      R(3))C6H2O-}, R(1) = NMe2, R(2) = N(i)Pr2, R(3) = R(4) = Cl (1), R(3) = R(4) =
      cumyl (3); R(1) = NMe2, R(2) = NEt2, R(3) = R(4) = cumyl (2), R(3) = CPh3, R(4) =
      Me (4); R(1) = NEt2, R(2) = NEt2, R(3) = CPh3, R(4) = Me (5); R(1) = NMe2, R(2) =
      (S)-1-butylpyrrolidin-2-yl, R(3) = R(4) = cumyl (6), R(3) = CPh3, R(4) = Me (7)],
      have been synthesized via reactions of Zn[N(SiMe3)2]2 and 1 equiv of the
      corresponding aminophenols. The monomeric nature and versatile coordination
      patterns of these complexes in the solid state were further confirmed by X-ray
      diffraction studies on complexes 2, 3, 5, and 7. In complex 3, the N,N
      diisopropylamino group on the pendant side arm does not coordinate to the metal
      center; only the remaining three donors of the aminophenolate ligand and the
      silylamido group interact with the zinc center. By contrast, in complexes 2, 5,
      and 7, the amino group of the aryl moiety does not coordinate to the metal
      center, while the amino group on the pendant side arm coordinates. At room
      temperature, the above-mentioned structural features of these complexes are
      retained in solution, as confirmed by (1)H NMR spectroscopy. Complexes 1-7 proved
      to be efficient initiators for the ring-opening polymerization of rac-lactide
      (rac-LA) at ambient temperature, and the polymerizations were better controlled
      in the presence of 2-propanol. The coordination pattern of the aminophenolate
      ligand exerted a significant influence on the stereoselectivity of the
      corresponding complex toward the polymerization of rac-LA, leading to the
      production of heterotactic biased polylactides (PLAs) by complexes 1 and 3 (Pm =
      0.40-0.46) and moderately to highly isotactic PLAs by complexes 2 and 4-7 (Pm =
      0.70-0.81). Detailed kinetic investigations revealed a first-order dependence on
      the monomer concentration for all complexes and different orders in the initiator
      concentration ranging from 1.78 to 1.81. The nature of the solvent as well as the
      molar ratio of the zinc complex and 2-propanol also displayed certain influence
      on the order of rac-LA polymerization in the initiator concentration. Factional
      orders of 1.80, 1.38, and 1.11 were obtained by using complex 5/(i)PrOH (1:1) in
      toluene and tetrahydrofuran and complex 5/(i)PrOH (1:2) in toluene, respectively.
      On the basis of DOSY and (1)H and (13)C NMR studies of zinc alkoxide model
      complexes "LZn(OCMe2COOMe)" as well as the fractional orders of 1.78-1.81 in the
      initiator concentration, activation/insertion processes likely involving more
      than one monomeric active species were then hypothesized. 

PMID- 25996448
TI  - Prioritization of therapy uncertainties in congenital ichthyosis: results from a
      Priority Setting Partnership.

PMID- 25996449
TI  - Self-assembled Monolayer Mediated Surface Environment Modification of
      Poly(vinylpyrrolidone)-Coated Hollow Au-Ag Nanoshells for Enhanced Loading of
      Hydrophobic Drug and Efficient Multimodal Therapy.
AB  - Hollow Au-Ag bimetallic nanoshell possessing hydrophobic interior space and
      hydrophilic exterior surface was prepared and its application as a chemo-thermo
      gene therapeutic agent based on its high payload of multiple drugs having
      different water solubility was demonstrated. The multifunctional drug delivery
      system is based on the hydrophobic interior created by the self-assembled
      monolayer (SAM) of hexanethiol onto the inner surface of the hollow metallic
      nanoshells whereas the outer surface was mostly coated by hydrophilic
      biocompatible polymer. The nanoshells having surface environment modified by
      hexanethiol SAMs provided high capacity both for hydrophilic DNAzyme (Dz) to
      induce gene silencing and for hydrophobic SN38 (7-ethyl-10-hydroxycamptothecin),
      anticancer drug. The release of the loaded Dz and SN38 was independently
      triggered by an acidic environment and by photothermal temperature elevation upon
      irradiation, respectively. The chemo-thermo-gene multitherapy based on the
      present nanoshells having modified surface environment showed high efficacy in
      quantitative cell-based assays using Huh7 human liver cell containing hepatitis C
      viral NS3 gene replicon RNA. 

PMID- 25996450
TI  - Longitudinal changes in handgrip strength, hyperinflation, and 6-minute walk
      distance in patients with COPD and a control group.
AB  - BACKGROUND: In COPD, a decreased inspiratory capacity to total lung capacity
      ratio (IC/TLC) is associated with dynamic hyperinflation and poor exercise
      capacity. The association with upper-extremity force measured by handgrip
      strength (HGS) and 6-min walk distance (6MWD) has not been previously described.
      We hypothesized that IC/TLC affects muscle strength in the upper and lower
      extremities, affecting HGS and 6MWD. METHODS: We prospectively measured lung
      function, HGS, and 6MWD in 27 patients with COPD and 12 healthy nonsmokers twice,
      1 year apart. The patients were classified according to level of hyperinflation:
      IC/TLC > 25% or IC/TLC <= 25%. RESULTS: Patients with COPD had reduced lung
      function, static hyperinflation, and reduced HGS and 6MWD compared with the
      control subjects on both evaluations (P < .01). There was a statistically
      significant deterioration in HGS, IC/TLC, and 6MWD after 1-year follow-up in the
      COPD compared with the control group (P < .001). More hyperinflation (IC/TLC <
      0.25) was associated with lower HGS and 6MWD (P < .001). Changes in IC/TLC
      correlated with changes in HGS (r = 0.429, P < .05). Multivariate analysis
      determined that IC/TLC is an independent factor associated with HSG and 6MWD.
      CONCLUSIONS: HGS and 6MWD are reduced in patients with COPD, particularly in
      those with hyperinflation and evidence of longitudinal deterioration not seen in
      control subjects. This finding suggests that resting hyperinflation may exert a
      detrimental effect on cardiac function and plays a role in reduced exercise
      performance in patients with COPD.

PMID- 25996452
TI  - Destabilization of Alzheimer's Abeta42 Protofibrils with a Novel Drug Candidate
      wgx-50 by Molecular Dynamics Simulations.
AB  - Alzheimer's disease (AD) is one of the most common dementia. The aggregation and
      deposition of the amyloid-beta peptide (Abeta) in neural tissue is its
      characteristic symptom. To destabilize and dissolve Abeta fibrils, a number of
      candidate molecules have been proposed. wgx-50 is a compound extracted from
      Sichuan pepper (Zanthoxylum bungeanum) and a potential candidate drug for
      treating AD. Our early experiments show it is effective in disassembling Abeta42
      aggregations. A series of molecular dynamics simulations were performed in this
      work to explain the molecular mechanism of the destabilization of Abeta42
      protofibril by wgx-50. It is found that there were three possible stable binding
      sites including two sites in hydrophobic grooves on surface of Abeta protofibril
      that made no significant changes in Abeta structures and one site in the interior
      that caused destabilization of the protofibril. In this site, wgx-50 was packed
      against the side chains of I32 and L34, disrupted the D23-K28 salt bridges, and
      partially opened the tightly compacted two beta-sheets. The results were
      confirmed by simulations at 320 K, where deeper insertion of wgx-50 into the
      whole protofibril was observed. The molecular mechanism of this novel drug
      candidate wgx-50 to disaggregate Abeta protofibril may provide some insight into
      the strategy of structure-based drug design for AD. 

PMID- 25996451
TI  - Ontario's emergency department process improvement program: the experience of
      implementation.
AB  - OBJECTIVES: In recent years, Lean manufacturing principles have been applied to
      health care quality improvement efforts to improve wait times. In Ontario, an
      emergency department (ED) process improvement program based on Lean principles
      was introduced by the Ministry of Health and Long-Term Care as part of a strategy
      to reduce ED length of stay (LOS) and to improve patient flow. This article aims
      to describe the hospital-based teams' experiences during the ED process
      improvement program implementation and the teams' perceptions of the key factors
      that influenced the program's success or failure. METHODS: A qualitative
      evaluation was conducted based on semistructured interviews with hospital
      implementation team members, such as team leads, medical leads, and executive
      sponsors, at 10 purposively selected hospitals in Ontario, Canada. Sites were
      selected based, in part, on their changes in median ED LOS following the
      implementation period. A thematic framework approach as used for interviews, and
      a standard thematic coding framework was developed. RESULTS: Twenty-four
      interviews were coded and analyzed. The results are organized according to
      participants' experience and are grouped into four themes that were identified as
      significantly affecting the implementation experience: local contextual factors,
      relationship between improvement team and support players, staff engagement, and
      success and sustainability. The results demonstrate the importance of the context
      of implementation, establishing strong relationships and communication
      strategies, and preparing for implementation and sustainability prior to the
      start of the project. CONCLUSIONS: Several key factors were identified as
      important to the success of the program, such as preparing for implementation,
      ensuring strong executive support, creation of implementation teams based on the
      tasks and outcomes of the initiative, and using multiple communication strategies
      throughout the implementation process. Explicit incorporation of these factors
      into the development and implementation of future similar interventions in health
      care settings could be useful.

PMID- 25996453
TI  - Synthesis of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives and
      their biological evaluation against protein tyrosine phosphatase 1B.
AB  - A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were
      designed, synthesized, and evaluated as a new class of inhibitors against protein
      tyrosine phosphatase 1B. Among them, compound 6f displayed moderate inhibitory
      activity with IC50 of 2.87 +/- 0.24 MUm and can be used as a novel lead compound
      for the design of inhibitors of protein tyrosine phosphatase 1B. 

PMID- 25996455
TI  - Small-world networks of residue interactions in the Abl kinase complexes with
      cancer drugs: topology of allosteric communication pathways can determine drug
      resistance effects.
AB  - The human protein kinases play a fundamental regulatory role in orchestrating
      functional processes in complex cellular networks. Understanding how
      conformational equilibrium between functional kinase states can be modulated by
      ligand binding or mutations is critical for quantifying molecular basis of
      allosteric regulation and drug resistance. In this work, molecular dynamics
      simulations of the Abl kinase complexes with cancer drugs (Imatinib and
      Dasatinib) were combined with structure-based network modeling to characterize
      dynamics of the residue interaction networks in these systems. The results have
      demonstrated that structural architecture of kinase complexes can produce a small
      world topology of the interaction networks. Our data have indicated that specific
      Imatinib binding to a small number of highly connected residues could lead to
      network-bridging effects and allow for efficient allosteric communication, which
      is mediated by a dominant pathway sensitive to the unphosphorylated Abl state. In
      contrast, Dasatinib binding to the active kinase form may activate a broader
      ensemble of allosteric pathways that are less dependent on the phosphorylation
      status of Abl and provide a better balance between the efficiency and resilience
      of signaling routes. Our results have unveiled how differences in the residue
      interaction networks and allosteric communications of the Abl kinase complexes
      can be directly related to drug resistance effects. This study offers a plausible
      perspective on how efficiency and robustness of the residue interaction networks
      and allosteric pathways in kinase structures may be associated with protein
      responses to drug binding. 

PMID- 25996456
TI  - Risk Communication, Values Clarification, and Vaccination Decisions.
AB  - Many health-related decisions require choosing between two options, each with
      risks and benefits. When presented with such tradeoffs, people often make choices
      that fail to align with scientific evidence or with their own values. This study
      tested whether risk communication and values clarification methods could help
      parents and guardians make evidence-based, values-congruent decisions about
      children's influenza vaccinations. In 2013-2014 we conducted an online 2*2
      factorial experiment in which a diverse sample of U.S. parents and guardians (n =
      407) were randomly assigned to view either standard information about influenza
      vaccines or risk communication using absolute and incremental risk formats.
      Participants were then either presented or not presented with an interactive
      values clarification interface with constrained sliders and dynamic visual
      feedback. Participants randomized to the risk communication condition combined
      with the values clarification interface were more likely to indicate intentions
      to vaccinate (beta = 2.10, t(399) = 2.63, p < 0.01). The effect was particularly
      notable among participants who had previously demonstrated less interest in
      having their children vaccinated against influenza (beta = -2.14, t(399) = -2.06,
      p < 0.05). When assessing vaccination status reported by participants who agreed
      to participate in a follow-up study six months later (n = 116), vaccination
      intentions significantly predicted vaccination status (OR = 1.66, 95%CI (1.13,
      2.44), p < 0.05) and rates of informed choice (OR = 1.51, 95%CI (1.07, 2.13), p <
      0.012), although there were no direct effects of experimental factors on
      vaccination rates. Qualitative analysis suggested that logistical barriers
      impeded immunization rates. Risk communication and values clarification methods
      may contribute to increased vaccination intentions, which may, in turn, predict
      vaccination status if logistical barriers are also addressed. 

PMID- 25996457
TI  - Switching to low dose of plasma-derived factor VIII/vWF concentrates with
      Confact((r)) -F as salvage immune tolerance induction in haemophilia A patients
      with inhibitors: five case reports from Japan.

PMID- 25996459
TI  - A pilot randomized controlled trial on the effectiveness of a 'lung age'
      intervention on smoking cessation: study protocol.
AB  - AIM: To evaluate the effectiveness of the 'lung age' intervention on smoking
      cessation rates, smoking abstinence self-efficacy, nicotine dependence and
      behavioural change among the smoking population in Singapore. BACKGROUND: Tobacco
      use has been linked to several preventable chronic diseases, such as
      cardiovascular diseases, stroke, cancers and respiratory diseases. Despite
      numerous health education attempts to promote smoking cessation, there has been a
      sustained increase in smoking rates worldwide, including in Singapore. DESIGN: A
      pilot randomized controlled trial. METHODS: A convenience sample of 108 smoking
      individuals will be recruited from population health screenings conducted by a
      tertiary public hospital in Singapore, with 54 participants in the experimental
      group and 54 in the control group. Participants in the experimental group will
      receive a lung age intervention, consisting of lung age determination and
      education as well as smoking cessation advice, while the researchers will provide
      those in the control group with the usual smoking education. Outcome measures
      include smoking cessation rates, smoking abstinence self-efficacy, nicotine
      dependence and assessment of the stages of behavioural change. Data will be
      collected at the baseline and again at the 3- and 6-month follow-ups. DISCUSSION:
      This study offers an additional intervention to improve smoking cessation rates
      in Singapore. It aims to reduce or delay the onset of smoking-related chronic
      diseases such as coronary heart diseases and cancer, which would eventually
      reduce the healthcare burden in an increasingly ageing society. TRIAL
      REGISTRATION NUMBER: ISRCTN15839687.

PMID- 25996458
TI  - A Multistate Investigation of Antibiotic-Resistant Salmonella enterica Serotype I
      4,[5],12:i:- Infections as Part of an International Outbreak Associated with
      Frozen Feeder Rodents.
AB  - While most human Salmonella infections result from exposure to contaminated
      foods, an estimated 11% of all Salmonella infections are attributed to animal
      exposures, including both direct animal handling and indirect exposures such as
      cleaning cages and handling contaminated pet food. This report describes the
      epidemiologic, environmental and laboratory investigations conducted in the
      United States as part of the response to an international outbreak of
      tetracycline-resistant Salmonella enterica serotype I 4,[5],12:i:- infections
      with over 500 illnesses occurring from 2008 to 2010. This investigation found
      that illness due to the outbreak strain was significantly associated with
      exposure to pet reptiles and frozen feeder rodents used as food for pet reptiles.
      Salmonella isolates indistinguishable from the outbreak strain were isolated from
      a frozen feeder mice-fed reptile owned by a case patient, as well as from frozen
      feeder mice and environmental samples collected from a rodent producing facility
      (Company A). An international voluntary recall of all Company A produced frozen
      feeder animals sold between May 2009 and July 2010 occurred. Only 13% of cases in
      our investigation were aware of the association between Salmonella infection and
      mice or rats. Consumers, the pet industry, healthcare providers and veterinarians
      need to be aware of the potential health risk posed by feeder rodents, whether
      live or frozen. Frozen feeder rodent producers, suppliers and distributors should
      follow the animal food labelling requirements as described in 21 CFR S501.5, and
      all packages of frozen feeder rodents should include safe handling instructions.
      Persons should wash their hands thoroughly with soap and water after handling
      live or frozen feeder rodents, as well as reptiles or anything in the area where
      the animals live. Continued opportunities exist for public health officials, the
      pet industry, veterinarians and consumers to work together to prevent
      salmonellosis associated with pet food, pets and other animals. 

PMID- 25996460
TI  - Impact of Professional Student Mentored Research Fellowship on Medical Education
      and Academic Medicine Career Path.
AB  - CONTEXT: This study explores the long-term impact of the Professional Student
      Mentored Research Fellowship (PSMRF) program at the University of Kentucky
      College of Medicine (UKCOM) on medical students' research productivity and career
      paths. METHODS: Demographic characteristics, academic profiles, number of
      publications and residency placements from 2007 to 2012 were used to assess 119
      PSMRF graduates against a comparison cohort of 898 UKCOM (non-PSMRF) students.
      RESULTS: PSMRF students had higher MCAT scores at admission (31.5 +/- 0.6 vs.
      30.6 +/- 0.2, p = 0.007) and achieved higher USMLE Step 1 scores (228 +/- 4.2 vs.
      223 +/- 1.5, p = 0.03) than comparison group. PSMRF students were more likely to
      publish PubMed-indexed papers (36.7% vs. 17.9%, p < 0.0001), achieve AOA status
      (19.3% vs. 8.5%, p = 0.0002) and match to top 25 US News and World Report
      residency programs (23.4% vs. 12.1%, p = 0.008). A greater proportion of PSMRF
      fellows matched to top tier competitive specialties (23% vs. 14.2%, p = 0.07),
      however this difference was not statistically significant. CONCLUSIONS: The PSMRF
      program shows a significant increase in enrollment, as well as positive
      associations with indicators of success in medical school and subsequent quality
      of residency program.

PMID- 25996461
TI  - Medical and Surgical Management of Carney Complex.
AB  - Carney complex is a rare, autosomal dominant genetic disorder that consists of
      multiple myxomatous lesions and endocrine abnormalities, including skin lesions,
      cardiac myxomas, primary pigmented nodular adrenocortical disease, and
      acromegaly. This review discusses the medical and surgical treatment of patients
      with Carney complex.

PMID- 25996462
TI  - Application of Coffee Silverskin in cosmetic formulations: physical/antioxidant
      stability studies and cytotoxicity effects.
AB  - CONTEXT: Currently, there is an increasing interest of cosmetic industry on
      natural extracts. The inclusion of antioxidants in topical formulations can
      contribute to minimize oxidative stress in the skin, which has been associated
      with aging. Also, questions of sustainability are leading to the study of new
      cosmetic ingredients obtained from food by-products. Coffee Silverskin (CS) is a
      food by-product with established antioxidant activity that has not yet been
      incorporated into a topical formulation. OBJECTIVE: The aim of this study was to
      evaluate the physical and microbiological stabilities and antioxidant activity of
      a hand cream formulation containing 2.5% (w/w) of CS extract upon production and
      after 6 months of shelf-life and in vitro safety/cytotoxicity on skin cell lines
      after production. MATERIALS AND METHODS: The in vitro cytotoxicity was evaluated
      with MTS and LDH assays, at different concentrations, in HaCaT and HFF-1 cells.
      Formulations were stored at 25  degrees C/65% RH and 40  degrees C/75% RH.
      Physical, microbiological, and antioxidant stabilities were evaluated by
      centrifugation, viscosity, total colony count, DPPH and total phenolic content
      (TPC). RESULTS: The hand cream containing 2.5% (w/w) of CS extract showed stable
      physical characteristics independently of the storage conditions. The DPPH
      activity and TPC of the CS formulation were significantly higher compared with
      those of the base formulation. However, during storage, the antioxidant activity
      decreases slightly. Microbiological quality was also confirmed. No cytotoxic
      effects were observed. CONCLUSION: It is possible to suggest that this
      formulation is stable under extreme conditions and safe for topical use.

PMID- 25996463
TI  - Lipid nanoparticles as an emerging platform for cannabinoid delivery:
      physicochemical optimization and biocompatibility.
AB  - This work aims at developing and optimizing a valuable oral delivery carrier for
      the cannabinoid derivative CB13, which presents a high therapeutic potential in
      chronic pain states that respond poorly to conventional analgesics, but also
      shows highly unfavorable physicochemical properties. CB13-loaded lipid
      nanoparticles (LNP) formulations were developed through solvent-emulsion
      evaporation and optimized in terms of physicochemical properties, long-term
      stability, integrity under gastric simulated conditions and in vitro interaction
      with NIH 3T3, HEK 293T and Caco-2 cells. An optimized formulation of LNP
      containing CB13 was obtained from a wide range of conditions assayed and
      analyzed. The selection of the lipid core, production conditions and the
      inclusion of lecithin proved to be key factors for the final properties of
      encapsulation, integrity and performance of the carriers. The LNP formulation
      proposed proved to be a promising carrier for the oral delivery of CB13, a
      cannabinoid with high therapeutic potential in chronic pain states that currently
      lack a valid oral treatment. 

PMID- 25996465
TI  - Successful Ablation of Atrial Fibrillation by Targeting Fractionation in a Left
      Sided Superior Vena Cava.

PMID- 25996464
TI  - The Influenza A PB1-F2 and N40 Start Codons Are Contained within an RNA
      Pseudoknot.
AB  - Influenza A is a negative-sense RNA virus with an eight-segment genome. Some
      segments encode more than one polypeptide product, but how the virus accesses
      alternate internal open reading frames (ORFs) is not completely understood. In
      segment 2, ribosomal scanning produces two internal ORFs, PB1-F2 and N40. Here,
      chemical mapping reveals a Mg(2+)-dependent pseudoknot structure that includes
      the PB1-F2 and N40 start codons. The results suggest that interactions of the
      ribosome with the pseudoknot may affect the level of translation for PB1-F2 and
      N40. 

PMID- 25996466
TI  - Probing the effects of mild traumatic brain injury with transcranial magnetic
      stimulation of the primary motor cortex.
AB  - PRIMARY OBJECTIVE: The present paper systematically reviews studies using
      transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) to
      assess cortical excitability, intra-cortical inhibition/facilitation and synaptic
      plasticity following mild traumatic brain injury (mTBI). METHODS: Articles using
      TMS over M1 in patients with mTBI or sport-related concussion indexed in PubMed
      and published between 1998 and September 2014 were included in the present
      review. MAIN OUTCOMES AND RESULTS: From the 17 articles that matched search
      criteria, results from various TMS paradigms were summarized and divided in three
      main areas of interest: motor cortical excitability/facilitation, motor cortical
      inhibition and cortical plasticity. Although studies suggest a trend of abnormal
      intra-cortical inhibition following mTBI, no clear and specific pattern emerges
      from the surveyed data. CONCLUSIONS: At this time and with the possible exception
      of intra-cortical inhibitory measures, TMS cannot reliably detect changes in M1
      excitability in individuals with mTBI or a concussion at both the acute and
      chronic stages of injury. This may be explained by the small number of studies
      and large variety of stimulation parameters. Additional longitudinal and
      multimodal studies are needed to better understand the nature of the excitability
      changes that may occur within M1 following mTBI.

PMID- 25996467
TI  - A preliminary psychometric evaluation of the interpersonal communication
      competence scale for aquired brain injury.
AB  - PRIMARY OBJECTIVE: To evaluate the psychometric properties of two adapted
      versions of the interpersonal communication competence scale (ICCS) that were
      applied to people with acquired brain injury (ABI). Construct validity was tested
      for both new scales and a factor extraction was performed on the proxy-rating
      version aiming to establish if it revealed meaningful constructs. METHODS: ICCS
      was translated from English to Danish language, pilot tested and slightly
      modified for use as a self-rating scale with people with ABI. A relative/staff
      version of the scale was also constructed for testing. Participants with medium
      to-severe ABI self-rated their interpersonal communication skills using the
      modified ICCS. Cronbach Alpha test was performed on both scales followed by a
      correlation analysis. RESULTS: Seventeen participants with medium-to-severe ABI
      and staff and relatives (n = 37) were involved in testing the ICCS-staff/relative
      rating and ICCS-self-rating. The ICCS-Staff/Relative showed an overall Cronbach
      alpha of alpha = 0.774 and the ICCS-Self-rating alpha = 0.675. A factor
      extraction of the ICCS-Staff/Relative revealed six meaningful sub-groups that
      corresponded well with the original ICCS. There was a low but significant
      correlation between the ratings performed by the two staff members most familiar
      with the participants (r = 0.280, p = 0.04). CONCLUSIONS: The ICCS-Staff/Relative
      revealed a good overall internal consistency, whereas the ICCS-Self-rating
      revealed acceptable internal consistency. The factor analysis of the proxy-rating
      revealed six meaningful sub-groups of interpersonal communication competencies.

PMID- 25996468
TI  - Factors affecting return to oral intake in inpatient rehabilitation after
      acquired brain injury.
AB  - PRIMARY OBJECTIVE: To extend previous observations by investigating if
      differences exist in time to initiation or to recovery of total oral intake in
      patients with acquired brain injury assessed by either Facial-Oral Tract Therapy
      (F.O.T.T.) or Fibreoptic Endoscopic Evaluation of Swallowing (FEES) and to
      investigate whether other factors influence these outcomes. RESEARCH DESIGN:
      Randomized controlled trial. METHODS: One hundred and nineteen patients with
      dysphagia in inpatient neurorehabilitation were randomized. The main outcome was
      time to maximum on the Functional Oral Intake Scale. RESULTS: There was no
      difference in time to initiation or recovery of total oral intake using F.O.T.T.
      or FEES. Oral intake was initiated for 42% on admission and 92% at discharge;
      2.5% of the patients were on total oral intake within 24 hours of admission and
      37% at discharge. The likelihood of recovery to total oral intake before
      discharge was found to depend on age, Functional Independence Measure score,
      length of stay and number of dysphagia interventions. CONCLUSION: There was no
      significant difference in time to initiation and recovery of total oral intake
      before discharge, whether assessed by F.O.T.T. or FEES, indicating that an
      instrumental assessment is unnecessary for standard evaluation. Age, functional
      independence and length of stay had a significant influence.

PMID- 25996469
TI  - Measuring task performance after acquired brain injury: Construct and concurrent
      validity of 'Upper Limb Performance Analysis'.
AB  - OBJECTIVE: This preliminary investigation studies selected aspects of validity of
      the Upper Limb Performance Analysis (ULPA), an occupation-based functional upper
      limb (UL) measure. METHODS: The study investigated the ULPA-Task Performance
      Mastery (ULPA-TPM) in 35 community dwelling adults with upper motor neuron
      syndrome following acquired brain injury and 26 healthy controls. Construct and
      concurrent validity of the ULPA were determined via group discrimination between
      adults with and without ABI; and ABI participants who were and were not referred
      for UL spasticity management with botulinum toxin-A injections (injected and non
      injected group). Concurrent validity was examined by investigating the
      relationships between the ULPA and an existing functional UL measure, the Action
      Research Arm Test, using Spearman's rank-order correlation. RESULTS: Significant
      differences in UL performance were demonstrated between the ABI and the Control
      group on all ULPA sub-scales (including: Omission (z = -2.6 to -3.6, rspb = 0.37
      0.48), Accuracy (z = -5.8 to -6.0, rspb = 0.78-0.82), Repetition (z = -5.1 to 
      5.4, rspb = 0.63-0.73) and Timing errors (z = -5.9 to -6.2, rspb = 0.77-0.88).
      Those in the Injected group demonstrated more task performance errors than the
      Non-injected group, with significant differences in Accuracy (z = -2.1 to -2.4,
      rspb = 0.37-0.45), Repetition (z = -2.5 to -2.1, rspb = 0.43) and Timing (z = 
      2.0, rspb = 0.37). CONCLUSIONS: This study demonstrated good construct and
      concurrent validity of the ULPA-TPM.

PMID- 25996470
TI  - The Spanish version of the Coma Recovery Scale-revised: Events on a correct
      timeline.

PMID- 25996471
TI  - TipC and the chorea-acanthocytosis protein VPS13A regulate autophagy in
      Dictyostelium and human HeLa cells.
AB  - Deficient autophagy causes a distinct phenotype in Dictyostelium discoideum,
      characterized by the formation of multitips at the mound stage. This led us to
      analyze autophagy in a number of multitipped mutants described previously (tipA(
      ), tipB(-), tipC(-), and tipD(-)). We found a clear autophagic dysfunction in
      tipC(-) and tipD(-) while the others showed no defects. tipD codes for a homolog
      of Atg16, which confirms the role of this protein in Dictyostelium autophagy and
      validates our approach. The tipC-encoded protein is highly similar to human
      VPS13A (also known as chorein), whose mutations cause the chorea-acanthocytosis
      syndrome. No member of the VPS13 protein family has been previously related to
      autophagy despite the presence of a region of similarity to Atg2 at the C
      terminus. This region also contains the conserved domain of unknown function
      DUF1162. Of interest, the expression of the TipC C-terminal coding sequence
      containing these 2 motifs largely complemented the mutant phenotype.
      Dictyostelium cells lacking TipC displayed a reduced number of autophagosomes
      visualized with the markers GFP-Atg18 and GFP-Atg8 and an impaired autophagic
      degradation as determined by a proteolytic cleavage assay. Downregulation of
      human VPS13A in HeLa cells by RNA interference confirmed the participation of the
      human protein in autophagy. VPS13A-depleted cells showed accumulation of
      autophagic markers and impaired autophagic flux. 

PMID- 25996473
TI  - Assessing and developing early careers in academic research: how can we improve
      the current systems?

PMID- 25996472
TI  - Humoral and cellular immune responses after influenza vaccination in patients
      with postcancer fatigue.
AB  - The aim of this study was to compare humoral and cellular immune responses to
      influenza vaccination in cancer survivors with and without severe symptoms of
      fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer
      survivors were vaccinated against seasonal influenza. Humoral immunity was
      evaluated at baseline and post-vaccination by a hemagglutination inhibition
      assay. Cellular immunity was evaluated at baseline and post-vaccination by
      lymphocyte proliferation and activation assays. Regulatory T cells were measured
      at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA.
      Comparable humoral immune responses were observed in fatigued and non-fatigued
      patients, both pre- and post-vaccination. At baseline, fatigued patients showed a
      significantly diminished cellular proliferation upon virus stimulation with
      strain H3N2 (1414 +/- 1201 counts), and a trend in a similar direction with
      strain H1N1 (3025 +/- 2339 counts), compared to non-fatigued patients (3099 +/-
      2401 and 5877 +/- 4604 counts, respectively). The percentage of regulatory T
      lymphocytes was significantly increased (4.4 +/- 2.1% versus 2.4 +/- 0.8%) and
      significantly lower amounts of interleukin 2 were detected prior to vaccination
      in fatigued compared to non-fatigued patients (36.3 +/- 44.3 pg/ml vs. 94.0 +/-
      45.4 pg/ml with strain H3N2 and 28.4 +/- 44.0 pg/ml versus 74.5 +/- 56.1 pg/ml
      with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations,
      post-vaccination cellular proliferation, and post-vaccination cytokine
      concentrations did not differ between both groups. In conclusion, influenza
      vaccination is favorable for severely fatigued cancer survivors and should be
      recommended when indicated. However, compared to non-fatigued cancer survivors,
      fatigued cancer survivors showed several significant differences in immunological
      reactivity at baseline, which warrants further investigation. 

PMID- 25996474
TI  - Dietary Factors Affecting Thyroid Cancer Risk: A Meta-Analysis.
AB  - Some dietary factors are proposed to affect thyroid carcinogenesis, but previous
      studies have reported inconsistent findings. Therefore, we performed a meta
      analysis, including 18 eligible studies, to clarify the role of dietary factors
      in the risk of thyroid cancer. The relative risks (RRs) with 95% confidence
      intervals (95% CIs) were estimated to assess the association and heterogeneity
      tests and subgroup and sensitivity analyses, and bias assessments were performed.
      When the results from all studies were combined, dietary iodine, fish, and
      cruciferous vegetable intake were not associated with thyroid cancer. However,
      when the data were divided by geographic location based on iodine availability, a
      slight increase in the risk of thyroid cancer was observed among those consuming
      a high total amount of fish in iodine nondeficient areas (RR: 1.18; 95% CI: 1.03
      1.35; P for heterogeneity = 0.282). When excluding the studies examining a single
      food item and hospital-based controls, a high intake of cruciferous vegetables
      was associated with an increased risk of thyroid cancer in iodine-deficient areas
      (RR: 1.43; 95% CI: 1.18-1.74; P for heterogeneity = 0.426). This meta-analysis
      implies that the role of dietary factors, such as fish and cruciferous
      vegetables, in thyroid cancer risk can differ based on iodine availability. 

PMID- 25996476
TI  - Welcome Back: Responses of Female Bonobos (Pan paniscus) to Fusions.
AB  - In species with a high degree of fission-fusion social dynamics, fusions may
      trigger social conflict and thus provide an opportunity to identify sources of
      social tension and mechanisms related to its alleviation. We characterized
      behavioral and endocrine responses of captive female bonobos (Pan paniscus) to
      fusions within a zoo facility designed to simulate naturalistic fission-fusion
      social dynamics. We compared urinary cortisol levels and frequencies of
      aggression, grooming and socio-sexual interactions between female bonobos while
      in stable sub-groups and when one "joiner" was reunited with the "residents" of
      another sub-group. We hypothesized that fusions would trigger increases in
      aggression and cortisol levels among reunited joiners and resident females. We
      further predicted that females who face more uncertainty in their social
      interactions following fusions may use grooming and/or socio-sexual behavior to
      reduce social tension and aggression. The only aggression on reunion days
      occurred between reunited females, but frequencies of aggression remained low
      across non-reunion and reunion days, and there was no effect of fusions on
      cortisol levels. Fusions did not influence patterns of grooming, but there were
      increases in socio-sexual solicitations and socio-sexual interactions between
      joiners and resident females. Joiners who had been separated from residents for
      longer received the most solicitations, but were also more selective in their
      acceptance of solicitations and preferred to have socio-sexual interactions with
      higher-ranking residents. Our results suggest that socio-sexual interactions play
      a role in reintegrating female bonobos into social groups following fusions. In
      addition, females who receive a high number of solicitations are able to gain
      more control over their socio-sexual interactions and may use socio-sexual
      interactions for other purposes, such as to enhance their social standing. 

PMID- 25996479
TI  - Correction: Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury
      independent of neutrophil infiltration.

PMID- 25996477
TI  - A peptide nucleic acid targeting nuclear RAD51 sensitizes multiple myeloma cells
      to melphalan treatment.
AB  - RAD51-mediated recombinational repair is elevated in multiple myeloma (MM) and
      predicts poor prognosis. RAD51 has been targeted to selectively sensitize and/or
      kill tumor cells. Here, we employed a peptide nucleic acid (PNA) to inhibit RAD51
      expression in MM cells. We constructed a PNA complementary to a unique segment of
      the RAD51 gene promoter, spanning the transcription start site, and conjugated it
      to a nuclear localization signal (PKKKRKV) to enhance cellular uptake and nuclear
      delivery without transfection reagents. This synthetic construct, (PNArad51_nls),
      significantly reduced RAD51 transcripts in MM cells, and markedly reduced the
      number and intensity of de novo and melphalan-induced nuclear RAD51 foci, while
      increasing the level of melphalan-induced gammaH2AX foci. Melphalan alone
      markedly induced the expression of 5 other genes involved in homologous
      recombination repair, yet suppression of RAD51 by PNArad51_nls was sufficient to
      synergize with melphalan, producing significant synthetic lethality of MM cells
      in vitro. In a SCID-rab mouse model mimicking the MM bone marrow
      microenvironment, treatment with PNArad51_nls +/- melphalan significantly
      suppressed tumor growth after 2 weeks, whereas melphalan plus control
      PNArad4u_nls was ineffectual. This study highlights the importance of RAD51 in
      myeloma growth and is the first to demonstrate that anti-RAD51 PNA can potentiate
      conventional MM chemotherapy. 

PMID- 25996481
TI  - An investigation on mechanical failure of hip joint using finite element method.
AB  - The aim of this work was to study how the stress distributions of the hip joint's
      components were changed if the activity was switched from walking to stair
      climbing for three different prostheses types subjected to either concentrated or
      distributed load. In the scope of the study, three different cemented prostheses,
      namely, Charnley, Muller, and Hipokrat were used for cemented total hip
      arthroplasty (THA) reconstruction. The finite element modeling of the hip joint
      with prosthesis was developed for both hip contact and muscle forces during
      walking and stair climbing activities. The finite element analyses were then
      pursued for both concentrated and distributed loading conditions applied
      statically on these models. Maximum von Mises stresses and strains occurred on
      the cortical and trabecular layers of bones; prosthesis and cement mantle were
      determined in order to investigate the mechanical failure of cemented THA
      reconstruction subjected to the different femoral loading and the activity
      conditions. This study showed that prosthesis, loading, and activity types had a
      significant effect on the stresses of components of the hip joint utilized for
      predicting mechanical failure of the cemented THA reconstruction. 

PMID- 25996483
TI  - Genetic aspects of intervertebral disc degeneration.
AB  - Intervertebral disc degeneration (IVDD) is one of the common causes of low back
      pain. Similar to many other multifactorial diseases, it is affected by
      environmental and genetic factors. Although not completely understood, genetic
      factors include a wide spectrum of variations, such as single nucleotide
      polymorphisms, which could play a significant role in the etiology of this
      disease. Besides, the interactions with environmental factors could make the role
      of genetic factors more complicated. Genetic variations in disc components could
      participate in developing degenerative disc disease through altering the normal
      homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III,
      IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X),
      enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem
      to play considerable roles in the pathology of this disease. There are also many
      other investigated genes that could somehow take part in the process. However, it
      seems that more studies are needed to clarify the exact role of genetics in IVDD.

PMID- 25996480
TI  - The papez circuit in first-episode, treatment-naive adults with major depressive
      disorder: combined atlas-based tract-specific quantification analysis and voxel
      based analysis.
AB  - Previous findings suggest that the Papez Circuit may have a role in major
      depressive disorders. We used atlas-based tract-specific quantification analysis
      and voxel-based analysis to examine the integrity of white matter tracts involved
      in mood regulation (including tracts in the Papez Circuit). Diffusion tensor
      imaging acquired from 35 first-episode, treatment-naive adults with major
      depressive disorders and 34 healthy adult controls were compared. Our statistical
      approach compared structural integrity of 11 major white matter tracts between
      the major depressive disorder and adult controls, as well as illness duration
      influence in patients. Fractional anisotropy was decreased in the hippocampal
      cingulum and in the anterior thalamic radiation according to both analytical
      approaches, all of which were important tracts included in the Papez Circuit. Our
      results support the role of the Papez Circuit in major depressive disorders with
      the minimal probability of false positive due to similar findings in both
      analyses that have complementary advantages. Dysfunction of the Papez Circuit may
      be a potential marker for studying the pathogenesis of major depressive
      disorders. 

PMID- 25996482
TI  - Radiostereometric migration analysis of the Cerafit femoral stem: 28 patients
      followed for 2 years.
AB  - Radiostereometric analysis (RSA) is the gold standard evaluating micromovements
      after total hip arthroplasty. The aim of this study was to investigate the
      migratory pattern of an uncemented femoral stem during the first 2 years after
      surgery. We followed 28 patients with a mean age of 57 (SD 13) years for the
      first two postoperative years. Radiostereometric analysis was used to measure the
      translation and rotation of the femoral component. The Harris hip score (HHS) was
      determined to evaluate the clinical outcome. No stem had to be revised. The mean
      HHS advanced from 35 (SD 11) preoperative to 89 (SD 10) 1 year after surgery. At
      the end of the observation period, mean subsidence of the stem was 0.26 mm (SD
      0.82). Maximum total point motion (MTPM) was 1.23 mm (SD 1.22). The main distal
      migration took place up to 6 weeks after surgery with nearly no further
      subsidence up to 2 years postoperatively. All the measured migrations of the hip
      stem were very small. Results of the HHS demonstrate good clinical outcome. Long
      term RSA is necessary to assess possible late migration of the Cerafit standard
      femoral stem. 

PMID- 25996484
TI  - High beta-glucosidase (GBA) activity not attributable to GBA1 and GBA2 in live
      normal and enzyme-deficient fibroblasts may emphasise the role of additional
      GBAs.
AB  - Beta-glucosidases (GBA) include GBA1, GBA2 and other beta-glucosidases (non-GBA1
      2). GBA1 is a lysosomal and GBA2 an extra-lysosomal enzyme. GBA1- and GBA2
      deficient genetic conditions, with different phenotypes, are glucosylceramide
      (GC; the main GBA substrate) accumulating diseases. To study the activity profile
      of GBA, live fibroblasts were loaded with radioactive GC. The GC metabolism was
      measured in wild-type, GBA1-deficient (Gaucher disease) and GBA2-deficient (Gba2(
      /- )mouse) cells. The differences found allowed the prediction of marked
      proportions of GBA1, GBA2, and particularly non-GBA1-2 (probably including GBA3,
      a cytosolic beta-glucosidase) activity for wild-type cells. The high proportion
      of non-GBA1-2 suggests an important role of these enzymes.

PMID- 25996485
TI  - Development of hemoglobin typing control materials for laboratory investigation
      of thalassemia and hemoglobinopathies.
AB  - BACKGROUND: To date, the hemoglobin (Hb) typing control materials for laboratory
      investigation of thalassemia with low (1.8%-3.2%) and high (4%-6%) levels of HbA2
      are available but there are no Hb typing quality control materials for analysis
      of thalassemia and hemoglobinopathies which are highly prevalent in South-East
      Asian countries. The main aim of the present study was to develop the lyophilized
      Hb typing control materials for laboratory investigation of thalassemia and
      hemoglobinopathies that are commonly found in South-East Asia. METHODS:
      Erythrocytes of blood samples containing Hb Bart's, HbH, HbE, HbF, Hb Constant
      Spring (CS), Hb Hope, and Hb Q-Thailand were washed and dialysed with 0.85%
      saline solution. The erythrocytes were then lysed in 5% sucrose solution. The
      lyophilized Hb typing control materials were prepared by using a freeze drying
      (lyophilization) method. The high performance liquid chromatography (HPLC)
      analysis of lyophilized Hb was performed after the storage at -20  degrees C for
      1 year and also after reconstitution and storage at 4 or -20  degrees C for 30
      days. In addition, the Hb analysis was compared between the three different
      methods of HPLC, low pressure liquid chromatography (LPLC) and capillary
      electrophoresis (CE). RESULTS: Following a year of storage at -20  degrees C, the
      HPLC chromatograms of lyophilized Hb typing control materials showed similar
      patterns to the equivalent fresh whole blood. The stability of reconstituted Hb
      typing control materials was also observed through 30 days after reconstitution
      and storage at -20  degrees C. Moreover, the Hb typing control materials could be
      analyzed by three methods, HPLC, LPLC and CE. Even a degraded peak of HbCS was
      found on CE electropherogram. CONCLUSIONS: The lyophilized Hb typing control
      materials could be developed and used as control materials for investigation of
      thalassemia and hemoglobinopathies.

PMID- 25996486
TI  - Creatinine, Jaffe, and glucose: another inconvenient truth.

PMID- 25996487
TI  - Evaluating and using innovative technologies: a lesson from Theranos?

PMID- 25996488
TI  - A message from the new Editor-in-Chief.

PMID- 25996489
TI  - Application of the extended clearance concept classification system (ECCCS) to
      predict the victim drug-drug interaction potential of statins.
AB  - BACKGROUND: During drug development, it is an important safety factor to identify
      the potential of new molecular entities to become a victim of drug-drug
      interactions (DDIs). In preclinical development, however, anticipation of
      clinical DDIs remains challenging due to the lack of in vivo human
      pharmacokinetic data. METHODS: We applied a recently developed in vitro-in vivo
      extrapolation method, including hepatic metabolism and transport processes,
      herein referred to as the Extended Clearance Concept Classification System
      (ECCCS). The human hepatic clearances and the victim DDI potentials were
      predicted for atorvastatin, cerivastatin, fluvastatin, lovastatin acid,
      pitavastatin, pravastatin, rosuvastatin, and simvastatin acid. RESULTS: Hepatic
      statin clearances were well-predicted by the ECCCS with six out of eight
      clearances projected within a two-fold deviation to reported values. In addition,
      worst-case DDI predictions were projected for each statin. Based on the ECCCS
      class assignment (4 classes), the mechanistic interplay of metabolic and
      transport processes, resulting in different DDI risks, was well-reflected by our
      model. Furthermore, predictions of clinically observed statins DDIs in
      combination with relevant perpetrator drugs showed good quantitative correlations
      with clinical observations. CONCLUSIONS: The ECCCS represents a powerful tool to
      anticipate the DDI potential of victim drugs based on in vitro drug metabolism
      and transport data.

PMID- 25996490
TI  - Population pharmacogenetics and global health.

PMID- 25996491
TI  - Glaucoma-Related Adverse Events in the First 5 Years After Unilateral Cataract
      Removal in the Infant Aphakia Treatment Study.
AB  - IMPORTANCE: Glaucoma-related adverse events constitute major sight-threatening
      complications of cataract removal in infancy, yet their relationship to aphakia
      vs primary intraocular lens (IOL) implantation remains unsettled. OBJECTIVE: To
      identify and characterize cases of glaucoma and glaucoma-related adverse events
      (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment
      Study by the age of 5 years. DESIGN, SETTING, AND PARTICIPANTS: A multicenter
      randomized clinical trial of 114 infants with unilateral congenital cataract in
      referral centers who were between ages 1 and 6 months at surgery. Mean follow-up
      was 4.8 years. This secondary analysis was conducted from December 23, 2004, to
      November 13, 2013. INTERVENTIONS: Participants were randomized at cataract
      surgery to either primary IOL or no IOL implantation (contact lens). Standardized
      definitions of glaucoma and glaucoma suspect were created for the Infant Aphakia
      Treatment Study and applied for surveillance and diagnosis. MAIN OUTCOMES AND
      MEASURES: Development of glaucoma and glaucoma + glaucoma suspect in operated on
      eyes for children up to age 5 years, plus intraocular pressure, visual acuity,
      and axial length at age 5 years. RESULTS: Product limit estimates of the risk for
      glaucoma and glaucoma + glaucoma suspect at 4.8 years after surgery were 17% (95%
      CI, 11%-25%) and 31% (95% CI, 24%-41%), respectively. The contact lens and IOL
      groups were not significantly different for either outcome: glaucoma (hazard
      ratio [HR], 0.8; 95% CI, 0.3-2.0; P = .62) and glaucoma + glaucoma suspect (HR,
      1.3; 95% CI, 0.6-2.5; P = .58). Younger (vs older) age at surgery conferred an
      increased risk for glaucoma (26% vs 9%, respectively) at 4.8 years after surgery
      (HR, 3.2; 95% CI, 1.2-8.3), and smaller (vs larger) corneal diameter showed an
      increased risk for glaucoma + glaucoma suspect (HR, 2.5; 95% CI, 1.3-5.0). Age
      and corneal diameter were significantly positively correlated. Glaucoma was
      predominantly open angle (19 of 20 cases, 95%), most eyes received medication (19
      of 20, 95%), and 8 of 20 eyes (40%) underwent surgery. CONCLUSIONS AND RELEVANCE:
      These results suggest that glaucoma-related adverse events are common and
      increase between ages 1 and 5 years in infants after unilateral cataract removal
      at 1 to 6 months of age; primary IOL placement does not mitigate their risk but
      surgery at a younger age increases the risk. Longer follow-up of these children
      may further characterize risk factors, long-term outcomes, potential differences
      between eyes having primary IOL vs aphakia, and optimal timing of unilateral
      congenital cataract removal. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00212134.

PMID- 25996492
TI  - Turning Escherichia coli into a Frataxin-Dependent Organism.
AB  - Fe-S bound proteins are ubiquitous and contribute to most basic cellular
      processes. A defect in the ISC components catalyzing Fe-S cluster biogenesis
      leads to drastic phenotypes in both eukaryotes and prokaryotes. In this context,
      the Frataxin protein (FXN) stands out as an exception. In eukaryotes, a defect in
      FXN results in severe defects in Fe-S cluster biogenesis, and in humans, this is
      associated with Friedreich's ataxia, a neurodegenerative disease. In contrast,
      prokaryotes deficient in the FXN homolog CyaY are fully viable, despite the clear
      involvement of CyaY in ISC-catalyzed Fe-S cluster formation. The molecular basis
      of the differing importance in the contribution of FXN remains enigmatic. Here,
      we have demonstrated that a single mutation in the scaffold protein IscU rendered
      E. coli viability strictly dependent upon a functional CyaY. Remarkably, this
      mutation changed an Ile residue, conserved in prokaryotes at position 108, into a
      Met residue, conserved in eukaryotes. We found that in the double mutant IscUIM
      DeltacyaY, the ISC pathway was completely abolished, becoming equivalent to the
      DeltaiscU deletion strain and recapitulating the drastic phenotype caused by FXN
      deletion in eukaryotes. Biochemical analyses of the "eukaryotic-like" IscUIM
      scaffold revealed that it exhibited a reduced capacity to form Fe-S clusters.
      Finally, bioinformatic studies of prokaryotic IscU proteins allowed us to trace
      back the source of FXN-dependency as it occurs in present-day eukaryotes. We
      propose an evolutionary scenario in which the current mitochondrial Isu proteins
      originated from the IscUIM version present in the ancestor of the Rickettsiae.
      Subsequent acquisition of SUF, the second Fe-S cluster biogenesis system, in
      bacteria, was accompanied by diminished contribution of CyaY in prokaryotic Fe-S
      cluster biogenesis, and increased tolerance to change in the amino acid present
      at the 108th position of the scaffold. 

PMID- 25996495
TI  - The Chlamydia pneumoniae Inclusion Membrane Protein Cpn1027 Interacts with Host
      Cell Wnt Signaling Pathway Regulator Cytoplasmic Activation/Proliferation
      Associated Protein 2 (Caprin2).
AB  - We previously identified hypothetical protein Cpn1027 as a novel inclusion
      membrane protein that is unique to Chlamydia pneumoniae. In the current study,
      using a yeast-two hybrid screen assay, we identified host cell cytoplasmic
      activation/proliferation-associated protein 2 (Caprin2) as an interacting partner
      of Cpn1027. The interaction was confirmed and mapped to the C-termini of both
      Cpn1027 and Caprin2 using co-immunoprecipitation and GST pull-down assays. A RFP
      Caprin2 fusion protein was recruited to the chlamydial inclusion and so was the
      endogenous GSK3beta, a critical component of the beta-catenin destruction complex
      in the Wnt signaling pathway. Cpn1027 also co-precipitated GSK3beta. Caprin2 is a
      key regulator of the Wnt signaling pathway by promoting the recruitment of the
      beta-catenin destruction complex to the cytoplasmic membrane in the presence of
      Wnt signaling while GSK3beta is required for priming beta-catenin for degradation
      in the absence of Wnt signaling. The Cpn1027 interactions with Caprin2 and
      GSK3beta may allow C. pneumoniae to actively sequester the beta-catenin
      destruction complex so that beta-catenin is maintained even in the absence of
      extracellular Wnt activation signals. The maintained beta-catenin can trans
      activate Wnt target genes including Bcl-2, which may contribute to the chlamydial
      antiapoptotic activity. We found that the C. pneumoniae-infected cells were more
      resistant to apoptosis induction and the anti-apoptotic activity was dependent on
      beta-catenin. Thus, the current study suggests that the chlamydial inclusion
      protein Cpn1027 may be able to manipulate host Wnt signaling pathway for
      enhancing the chlamydial anti-apoptotic activity. 

PMID- 25996497
TI  - Furthering the Understanding of Actions of Botulinum Toxin A.

PMID- 25996493
TI  - Risk associated with bee venom therapy: a systematic review and meta-analysis.
AB  - OBJECTIVE: The safety of bee venom as a therapeutic compound has been extensively
      studied, resulting in the identification of potential adverse events, which range
      from trivial skin reactions that usually resolve over several days to life
      threating severe immunological responses such as anaphylaxis. In this systematic
      review, we provide a summary of the types and prevalence of adverse events
      associated with bee venom therapy. METHODS: We searched the literature using 12
      databases from their inception to June 2014, without language restrictions. We
      included all types of clinical studies in which bee venom was used as a key
      intervention and adverse events that may have been causally related to bee venom
      therapy were reported. RESULTS: A total of 145 studies, including 20 randomized
      controlled trials, 79 audits and cohort studies, 33 single-case studies, and 13
      case series, were evaluated in this review. The median frequency of patients who
      experienced adverse events related to venom immunotherapy was 28.87%
      (interquartile range, 14.57-39.74) in the audit studies. Compared with normal
      saline injection, bee venom acupuncture showed a 261% increased relative risk for
      the occurrence of adverse events (relative risk, 3.61; 95% confidence interval,
      2.10 to 6.20) in the randomized controlled trials, which might be overestimated
      or underestimated owing to the poor reporting quality of the included studies.
      CONCLUSIONS: Adverse events related to bee venom therapy are frequent; therefore,
      practitioners of bee venom therapy should be cautious when applying it in daily
      clinical practice, and the practitioner's education and qualifications regarding
      the use of bee venom therapy should be ensured.

PMID- 25996496
TI  - Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide
      Nanomaterials: First Steps towards an Intelligent Testing Strategy.
AB  - Nanomaterials (NMs) display many unique and useful physico-chemical properties.
      However, reliable approaches are needed for risk assessment of NMs. The present
      study was performed in the FP7-MARINA project, with the objective to identify and
      evaluate in vitro test methods for toxicity assessment in order to facilitate the
      development of an intelligent testing strategy (ITS). Six representative oxide
      NMs provided by the EC-JRC Nanomaterials Repository were tested in nine
      laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models
      representing 6 different target organs/systems (immune system, respiratory
      system, gastrointestinal system, reproductive organs, kidney and embryonic
      tissues). The toxicity assessment was conducted using 10 different assays for
      cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and
      oxidative stress. Thorough physico-chemical characterization was performed for
      all tested NMs. Commercially relevant NMs with different physico-chemical
      properties were selected: two TiO2 NMs with different surface chemistry -
      hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO - uncoated (NM
      110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by
      two different manufacturing techniques - precipitated (NM-200) and pyrogenic (NM
      203). Cell specific toxicity effects of all NMs were observed; macrophages were
      the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2).
      Longer term exposure (7 to 21 days) significantly affected the cell barrier
      integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem
      cell test (EST) classified the TiO2 NMs as potentially 'weak-embryotoxic' and ZnO
      and SiO2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the
      representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 >
      TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic
      tissues, for which TiO2 displayed higher toxicity compared with ZnO and SiO2.
      Importantly, the in vitro methodology applied could identify cell- and NM
      specific responses, with a low variability observed between different test
      assays. Overall, this testing approach, based on a battery of cellular systems
      and test assays, complemented by an exhaustive physico-chemical characterization
      of NMs, could be deployed for the development of an ITS suitable for risk
      assessment of NMs. This study also provides a rich source of data for modeling of
      NM effects. 

PMID- 25996498
TI  - Cardiac beta-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as
      Type-2 Diabetes Progresses.
AB  - OBJECTIVES: Reduced cardiac beta-adrenoceptor (beta-AR) expression and
      cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia.
      Cardiac beta-AR expression in type-2 diabetes models of hyperglycemia and
      hyperinsulinemia, remain less clear. This study investigates cardiac beta-AR
      expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats. METHODS: Ex vivo
      biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL)
      and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body
      mass, and diet consumption were measured. Western blotting of beta-AR subtypes
      was completed in parallel. Echocardiography was performed at 10 and 16 weeks to
      assess systolic and diastolic function. Fasted plasma insulin, free fatty acids
      (FFA), leptin and fed-state insulin were also measured. RESULTS: At 10 weeks,
      myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17+/-4.1mM) compared to
      ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22+/
      2.4mM) progressed. Reduced beta-AR expression not apparent at 10 weeks also
      developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western
      blotting at 10 weeks indicated normal beta1-AR (98+/-9%), reduced beta2-AR (76+/
      10%), and elevated beta3-AR (108+/-6). At 16 weeks, beta1-AR expression became
      reduced (69+/-16%), beta2-AR expression decreased further (68+/-14%), and beta3
      AR remained elevated, similar to 10 weeks (112+/-9%). While HR was reduced at 10
      and 16 weeks in ZDF rats, no significant changes were observed in diastolic or
      systolic function. CONCLUSIONS: Cardiac beta-AR are reduced over 6 weeks of
      sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac
      [3H]CGP12177 retention and beta1- and beta2-AR expression are inversely
      correlated with the progression of type-2 diabetes.

PMID- 25996499
TI  - The spread of multi drug resistant infections is leading to an increase in the
      empirical antibiotic treatment failure in cirrhosis: a prospective survey.
AB  - BACKGROUND: The spread of multi-resistant infections represents a continuously
      growing problem in cirrhosis, particularly in patients in contact with the
      healthcare environment. AIM: Our prospective study aimed to analyze epidemiology,
      prevalence and risk factors of multi-resistant infections, as well as the rate of
      failure of empirical antibiotic therapy in cirrhotic patients. METHODS: All
      consecutive cirrhotic patients hospitalized between 2008 and 2013 with a
      microbiologically-documented infection (MDI) were enrolled. Infections were
      classified as Community-Acquired (CA), Hospital-Acquired (HA) and Healthcare
      Associated (HCA). Bacteria were classified as Multidrug-Resistant (MDR) if
      resistant to at least three antimicrobial classes, Extensively-Drug-Resistant
      (XDR) if only sensitive to one/two classes and Pandrug-Resistant (PDR) if
      resistant to all classes. RESULTS: One-hundred-twenty-four infections (15% CA,
      52% HA, 33% HCA) were observed in 111 patients. Urinary tract infections,
      pneumonia and spontaneous bacterial peritonitis were the more frequent. Forty
      seven percent of infections were caused by Gram-negative bacteria. Fifty-one
      percent of the isolates were multi-resistant to antibiotic therapy (76% MDR, 21%
      XDR, 3% PDR): the use of antibiotic prophylaxis (OR = 8.4; 95%CI = 1.03-76; P =
      0,05) and current/recent contact with the healthcare-system (OR = 3.7; 95%CI =
      1.05-13; P = 0.04) were selected as independent predictors. The failure of the
      empirical antibiotic therapy was progressively more frequent according to the
      degree of resistance. The therapy was inappropriate in the majority of HA and HCA
      infections. CONCLUSIONS: Multi-resistant infections are increasing in
      hospitalized cirrhotic patients. A better knowledge of the epidemiological
      characteristics is important to improve the efficacy of empirical antibiotic
      therapy. The use of preventive measures aimed at reducing the spread of multi
      resistant bacteria is also essential.

PMID- 25996500
TI  - The effect of intra-articular injection of Diprospan at the knee joint on the
      hypothalamic-pituitary-adrenal axis.
AB  - QUESTIONS UNDER STUDY: In this work we wanted to evaluate the effect of intra
      articular injection (IAI) at the knee joint of 1 ml of Diprospan on the
      hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Consecutive patients
      attending the rheumatology or orthopaedic clinic with osteoarthritic knee pain
      not responding satisfactorily to medical and physical therapy were asked to
      participate in our study. After consent, patients had ultrasound-guided IAI of 1
      ml of Diprospan, containing 2 mg of betamethasone sodium phosphate and 5 mg of
      betamethasone dipropionate. Demographic, clinical, laboratory and radiographic
      variables were documented. Just prior to the knee injection and 1, 2, 4 and 6
      weeks later, patients had a 1-ug adrenocorticotropic hormone (ACTH) stimulation
      test. Secondary adrenal insufficiency (SAI) was defined as a poststimulation (30
      minutes after ACTH injection) serum cortisol level of less than 18 ug/dl (~500
      nmol/l) and lack of a rise of >6 ug/dl (~166 nmol/l) over the basal level in
      poststimulation serum cortisol. RESULTS: Twenty patients completed the study.
      There were 3 male and 17 female patients, with a mean age of 58.6+/-9.5 years.
      Six (30%) patients had evidence of SAI and in five of them it was seen at one
      time-point, mostly at week 2 after the IAI. In one patient, SAI was prolonged and
      observed from week 1 to week 4. CONCLUSIONS: IAI at the knee joint of 1 ml of
      Diprospan was associated with a transient high rate of SAI.

PMID- 25996501
TI  - Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR
      Activity.
AB  - The mammalian target of rapamycin (mTOR) regulates the motility and invasion of
      cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The
      previous study had proved that the anti-tumor effect of cardamonin was associated
      with mTOR inhibition. In the present study, the anti-metastatic effect of
      cardamonin and its underlying molecule mechanisms were investigated on the highly
      metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and
      migration of LLC cells were measured by MTT, transwell and wound healing assays,
      respectively. The expression and activation of mTOR- and adhesion-related
      proteins were assessed by Western blotting. The in vivo effect of cardamonin on
      the metastasis of the LLC cells was investigated by a mouse model. Treated with
      cardamonin, the proliferation, invasion and migration of LLC cells were
      significantly inhibited. The expression of Snail was decreased by cardamonin,
      while that of E-cadherin was increased. In addition, cardamonin inhibited the
      activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1).
      Furthermore, the tumor growth and its lung metastasis were inhibited by
      cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion
      and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory
      effect of cardamonin was correlated with down-regulation of Snail and up
      regulation of E-cadherin. 

PMID- 25996502
TI  - Individual-area relationship best explains goose species density in wetlands.
AB  - Explaining and predicting animal distributions is one of the fundamental
      objectives in ecology and conservation biology. Animal habitat selection can be
      regulated by top-down and bottom-up processes, and is mediated by species
      interactions. Species varying in body size respond differently to top-down and
      bottom-up determinants, and hence understanding these allometric responses to
      those determinants is important for conservation. In this study, using two
      differently sized goose species wintering in the Yangtze floodplain, we tested
      the predictions derived from three different hypotheses (individual-area
      relationship, food resource and disturbance hypothesis) to explain the spatial
      and temporal variation in densities of two goose species. Using Generalized
      Linear Mixed Models with a Markov Chain Monte Carlo technique, we demonstrated
      that goose density was positive correlated with patch area size, suggesting that
      the individual area-relationship best predicts differences in goose densities.
      Moreover, the other predictions, related to food availability and disturbance,
      were not significant. Buffalo grazing probably facilitated greater white-fronted
      geese, as the number of buffalos was positively correlated to the density of this
      species. We concluded that patch area size is the most important factor
      determining the density of goose species in our study area. Patch area size is
      directly determined by water levels in the Yangtze floodplain, and hence
      modifying the hydrological regimes can enlarge the capacity of these wetlands for
      migratory birds. 

PMID- 25996503
TI  - Is the cellular initiation of translation an exclusive property of the initiator
      tRNAs?
AB  - Translation of mRNAs is the primary function of the ribosomal machinery. Although
      cells allow for a certain level of translational errors/mistranslation (which may
      well be a strategic need), maintenance of the fidelity of translation is vital
      for the cellular function and fitness. The P-site bound initiator tRNA selects
      the start codon in an mRNA and specifies the reading frame. A direct P-site
      binding of the initiator tRNA is a function of its special structural features,
      ribosomal elements, and the initiation factors. A highly conserved feature of the
      3 consecutive G:C base pairs (3 GC pairs) in the anticodon stem of the initiator
      tRNAs is vital in directing it to the P-site. Mutations in the 3 GC pairs
      diminish/abolish initiation under normal physiological conditions. Using
      molecular genetics approaches, we have identified conditions that allow
      initiation with the mutant tRNAs in Escherichia coli. During our studies, we have
      uncovered a novel phenomenon of in vivo initiation by elongator tRNAs. Here, we
      recapitulate how the cellular abundance of the initiator tRNA, and nucleoside
      modifications in rRNA are connected with the tRNA selection in the P-site. We
      then discuss our recent finding of how a conserved feature in the mRNA, the Shine
      Dalgarno sequence, influences tRNA selection in the P-site.

PMID- 25996504
TI  - Where Do Ethno-Linguistic Groups Meet? How Copresence during Free-Time Is Related
      to Copresence at Home and at Work.
AB  - This paper analyzes ethnic segregation across the whole activity space-at place
      of residence, place of work, and during free-time. We focus on interethnic
      meeting potential during free-time, measured as copresence, and its relationship
      to copresence at place of residence and work. The study is based on cellphone
      data for a medium-sized linguistically divided European city (Tallinn, Estonia),
      where the Estonian majority and mainly Russian-speaking minority populations are
      of roughly equal size. The results show that both places of residence and work
      are segregated, while other activities occur in a far more integrated
      environment. Copresence during free-time is positively associated with copresence
      at place of residence and work, however, the relationship is very weak. 

PMID- 25996506
TI  - Exploring Bodies in Southern and East Africa.

PMID- 25996505
TI  - Biodistribution and trafficking of hydrogel nanoparticles in adult mosquitoes.
AB  - BACKGROUND: Nanotechnology offers great potential for molecular genetic
      investigations and potential control of medically important arthropods. Major
      advances have been made in mammalian systems to define nanoparticle (NP)
      characteristics that condition trafficking and biodistribution of NPs in the
      host. Such information is critical for effective delivery of therapeutics and
      molecules to cells and organs, but little is known about biodistribution of NPs
      in mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: PRINT technology was used to
      construct a library of fluorescently labeled hydrogel NPs of defined size, shape,
      and surface charge. The biodistribution (organ, tissue, and cell tropisms and
      trafficking kinetics) of positively and negatively charged 200 nm x 200 nm, 80 nm
      x 320 nm, and 80 nm x 5000 nm NPs was determined in adult Anopheles gambiae
      mosquitoes as a function of the route of challenge (ingestion, injection or
      contact) using whole body imaging and fluorescence microscopy. Mosquitoes readily
      ingested NPs in sugar solution. Whole body fluorescence imaging revealed
      substantial NP accumulation (load) in the alimentary tracts of the adult
      mosquitoes, with the greatest loads in the diverticula, cardia and foregut.
      Positively and negatively charged NPs differed in their biodistribution and
      trafficking. Following oral challenge, negatively charged NPs transited the
      alimentary tract more rapidly than positively charged NPs. Following contact
      challenge, negatively charged NPs trafficked more efficiently in alimentary tract
      tissues. Following parenteral challenge, positively and negatively charged NPs
      differed in tissue tropisms and trafficking in the hemocoel. Injected NPs were
      also detected in cardia/foregut, suggesting trafficking of NPs from the hemocoel
      into the alimentary tract. CONCLUSIONS/SIGNIFICANCE: Herein we have developed a
      tool box of NPs with the biodistribution and tissue tropism characteristics for
      gene structure/function studies and for delivery of vector lethal cargoes for
      mosquito control.

PMID- 25996507
TI  - The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus
      Macaques Suppresses SAMHD1 in CD4+ Memory T Cells.
AB  - For nearly 20 years, the principal biological function of the HIV-2/SIV Vpx gene
      has been thought to be required for optimal virus replication in myeloid cells.
      Mechanistically, this Vpx activity was recently reported to involve the
      degradation of Sterile Alpha Motif and HD domain-containing protein 1 (SAMHD1) in
      this cell lineage. Here we show that when macaques were inoculated with either
      the T cell tropic SIVmac239 or the macrophage tropic SIVmac316 carrying a Vpx
      point mutation that abrogates the recruitment of DCAF1 and the ensuing
      degradation of endogenous SAMHD1 in cultured CD4+ T cells, virus acquisition,
      progeny virion production in memory CD4+ T cells during acute infection, and the
      maintenance of set-point viremia were greatly attenuated. Revertant viruses
      emerging in two animals exhibited an augmented replication phenotype in memory
      CD4+ T lymphocytes both in vitro and in vivo, which was associated with reduced
      levels of endogenous SAMHD1. These results indicate that a critical role of Vpx
      in vivo is to promote the degradation of SAMHD1 in memory CD4+ T lymphocytes,
      thereby generating high levels of plasma viremia and the induction of
      immunodeficiency. 

PMID- 25996508
TI  - A Wearable Context-Aware ECG Monitoring System Integrated with Built-in Kinematic
      Sensors of the Smartphone.
AB  - Continuously monitoring the ECG signals over hours combined with activity status
      is very important for preventing cardiovascular diseases. A traditional ECG
      holter is often inconvenient to carry because it has many electrodes attached to
      the chest and because it is heavy. This work proposes a wearable, low power
      context-aware ECG monitoring system integrated built-in kinetic sensors of the
      smartphone with a self-designed ECG sensor. The wearable ECG sensor is comprised
      of a fully integrated analog front-end (AFE), a commercial micro control unit
      (MCU), a secure digital (SD) card, and a Bluetooth module. The whole sensor is
      very small with a size of only 58 * 50 * 10 mm for wearable monitoring
      application due to the AFE design, and the total power dissipation in a full
      round of ECG acquisition is only 12.5 mW. With the help of built-in kinetic
      sensors of the smartphone, the proposed system can compute and recognize user's
      physical activity, and thus provide context-aware information for the continuous
      ECG monitoring. The experimental results demonstrated the performance of proposed
      system in improving diagnosis accuracy for arrhythmias and identifying the most
      common abnormal ECG patterns in different activities. In conclusion, we provide a
      wearable, accurate and energy-efficient system for long-term and context-aware
      ECG monitoring without any extra cost on kinetic sensor design but with the help
      of the widespread smartphone. 

PMID- 25996509
TI  - A Flexible Three-in-One Microsensor for Real-Time Monitoring of Internal
      Temperature, Voltage and Current of Lithium Batteries.
AB  - Lithium batteries are widely used in notebook computers, mobile phones, 3C
      electronic products, and electric vehicles. However, under a high
      charge/discharge rate, the internal temperature of lithium battery may rise
      sharply, thus causing safety problems. On the other hand, when the lithium
      battery is overcharged, the voltage and current may be affected, resulting in
      battery instability. This study applies the micro-electro-mechanical systems
      (MEMS) technology on a flexible substrate, and develops a flexible three-in-one
      microsensor that can withstand the internal harsh environment of a lithium
      battery and instantly measure the internal temperature, voltage and current of
      the battery. Then, the internal information can be fed back to the outside in
      advance for the purpose of safety management without damaging the lithium battery
      structure. The proposed flexible three-in-one microsensor should prove helpful
      for the improvement of lithium battery design or material development in the
      future. 

PMID- 25996510
TI  - Photonic crystal fiber-based surface plasmon resonance sensor with selective
      analyte channels and graphene-silver deposited core.
AB  - We propose a surface plasmon resonance (SPR) sensor based on photonic crystal
      fiber (PCF) with selectively filled analyte channels. Silver is used as the
      plasmonic material to accurately detect the analytes and is coated with a thin
      graphene layer to prevent oxidation. The liquid-filled cores are placed near to
      the metallic channel for easy excitation of free electrons to produce surface
      plasmon waves (SPWs). Surface plasmons along the metal surface are excited with a
      leaky Gaussian-like core guided mode. Numerical investigations of the fiber's
      properties and sensing performance are performed using the finite element method
      (FEM). The proposed sensor shows maximum amplitude sensitivity of 418 Refractive
      Index Units (RIU-1) with resolution as high as 2.4 * 10(-5) RIU. Using the
      wavelength interrogation method, a maximum refractive index (RI) sensitivity of
      3000 nm/RIU in the sensing range of 1.46-1.49 is achieved. The proposed sensor is
      suitable for detecting various high RI chemicals, biochemical and organic
      chemical analytes. Additionally, the effects of fiber structural parameters on
      the properties of plasmonic excitation are investigated and optimized for sensing
      performance as well as reducing the sensor's footprint.

PMID- 25996511
TI  - Design of a novel telerehabilitation system with a force-sensing mechanism.
AB  - Many stroke patients are expected to rehabilitate at home, which limits their
      access to proper rehabilitation equipment, treatment, or assessment by
      therapists. We have developed a novel telerehabilitation system that incorporates
      a human-upper-limb-like device and an exoskeleton device. The system is designed
      to provide the feeling of real therapist-patient contact via telerehabilitation.
      We applied the principle of a series elastic actuator to both the master and
      slave devices. On the master side, the therapist can operate the device in a
      rehabilitation center. When performing passive training, the master device can
      detect the therapist's motion while controlling the deflection of elastic
      elements to near-zero, and the patient can receive the motion via the exoskeleton
      device. When performing active training, the design of the force-sensing
      mechanism in the master device can detect the assisting force added by the
      therapist. The force-sensing mechanism also allows force detection with an angle
      sensor. Patients' safety is guaranteed by monitoring the motor's current from the
      exoskeleton device. To compensate for any possible time delay or data loss, a
      torque-limiter mechanism was also designed in the exoskeleton device for
      patients' safety. Finally, we successfully performed a system performance test
      for passive training with transmission control protocol/internet protocol
      communication. 

PMID- 25996512
TI  - Semi-supervised Bayesian classification of materials with impact-echo signals.
AB  - The detection and identification of internal defects in a material require the
      use of some technology that translates the hidden interior damages into
      observable signals with different signature-defect correspondences. We apply
      impact-echo techniques for this purpose. The materials are classified according
      to their defective status (homogeneous, one defect or multiple defects) and kind
      of defect (hole or crack, passing through or not). Every specimen is impacted by
      a hammer, and the spectrum of the propagated wave is recorded. This spectrum is
      the input data to a Bayesian classifier that is based on the modeling of the
      conditional probabilities with a mixture of Gaussians. The parameters of the
      Gaussian mixtures and the class probabilities are estimated using an extended
      expectation-maximization algorithm. The advantage of our proposal is that it is
      flexible, since it obtains good results for a wide range of models even under
      little supervision; e.g., it obtains a harmonic average of precision and recall
      value of 92.38% given only a 10% supervision ratio. We test the method with real
      specimens made of aluminum alloy. The results show that the algorithm works very
      well. This technique could be applied in many industrial problems, such as the
      optimization of the marble cutting process. 

PMID- 25996513
TI  - Towards the automatic scanning of indoors with robots.
AB  - This paper is framed in both 3D digitization and 3D data intelligent processing
      research fields. Our objective is focused on developing a set of techniques for
      the automatic creation of simple three-dimensional indoor models with mobile
      robots. The document presents the principal steps of the process, the
      experimental setup and the results achieved. We distinguish between the stages
      concerning intelligent data acquisition and 3D data processing. This paper is
      focused on the first stage. We show how the mobile robot, which carries a 3D
      scanner, is able to, on the one hand, make decisions about the next best scanner
      position and, on the other hand, navigate autonomously in the scene with the help
      of the data collected from earlier scans. After this stage, millions of 3D data
      are converted into a simplified 3D indoor model. The robot imposes a stopping
      criterion when the whole point cloud covers the essential parts of the scene.
      This system has been tested under real conditions indoors with promising results.
      The future is addressed to extend the method in much more complex and larger
      scenarios. 

PMID- 25996514
TI  - Real-time oil-saturation monitoring in rock cores with low-field NMR.
AB  - Nuclear magnetic resonance (NMR) provides a powerful suite of tools for studying
      oil in reservoir core plugs at the laboratory scale. Low-field magnets are
      preferred for well-log calibration and to minimize magnetic-susceptibility
      induced internal gradients in the porous medium. We demonstrate that careful data
      processing, combined with prior knowledge of the sample properties, enables real
      time acquisition and interpretation of saturation state (relative amount of oil
      and water in the pores of a rock). Robust discrimination of oil and brine is
      achieved with diffusion weighting. We use this real-time analysis to monitor the
      forced displacement of oil from porous materials (sintered glass beads and
      sandstones) and to generate capillary desaturation curves. The real-time output
      enables in situ modification of the flood protocol and accurate control of the
      saturation state prior to the acquisition of standard NMR core analysis data,
      such as diffusion-relaxation correlations. Although applications to oil recovery
      and core analysis are demonstrated, the implementation highlights the general
      practicality of low-field NMR as an inline sensor for real-time industrial
      process control. 

PMID- 25996515
TI  - Transfer Rate Edited experiment for the selective detection of Chemical Exchange
      via Saturation Transfer (TRE-CEST).
AB  - Chemical Exchange Saturation Transfer (CEST) magnetic resonance experiments have
      become valuable tools in magnetic resonance for the detection of low
      concentration solutes with far greater sensitivity than direct detection methods.
      Accurate measures of rates of chemical exchange provided by CEST are of
      particular interest to biomedical imaging communities where variations in
      chemical exchange can be related to subtle variations in biomarker concentration,
      temperature and pH within tissues using MRI. Despite their name, however,
      traditional CEST methods are not truly selective for chemical exchange and
      instead detect all forms of magnetization transfer including through-space NOE.
      This ambiguity crowds CEST spectra and greatly complicates subsequent data
      analysis. We have developed a Transfer Rate Edited CEST experiment (TRE-CEST)
      that uses two different types of solute labeling in order to selectively amplify
      signals of rapidly exchanging proton species while simultaneously suppressing
      'slower' NOE-dominated magnetization transfer processes. This approach is
      demonstrated in the context of both NMR and MRI, where it is used to detect the
      labile amide protons of proteins undergoing chemical exchange (at rates?30s(-1))
      while simultaneously eliminating signals originating from slower (~5s(-1)) NOE
      mediated magnetization transfer processes. TRE-CEST greatly expands the utility
      of CEST experiments in complex systems, and in-vivo, in particular, where it is
      expected to improve the quantification of chemical exchange and magnetization
      transfer rates while enabling new forms of imaging contrast. 

PMID- 25996516
TI  - Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects
      of cacao polyphenol.
AB  - Here, we investigated the protective effect of cacao polyphenol extract (CPE) on
      carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats
      were administered CPE for 7 days and then received intraperitoneal injection of
      CCl4. Two hours after injection, we found that CCl4 treatment significantly
      increased biochemical injury markers, lipid peroxides (phosphatidylcholine
      hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione
      peroxidase activity in kidney rather than liver, suggesting that kidney is more
      vulnerable to oxidative stress under the present experimental conditions. CPE
      supplementation significantly reduced these changes, indicating that this
      compound has antioxidant properties against CCl4-induced oxidative stress. An
      inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an
      explanation for CPE antioxidant property. Together, these results provide
      quantitative evidence of the in vivo antioxidant properties of CPE, especially in
      terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats.

PMID- 25996517
TI  - Sterol Composition and Biosynthetic Genes of Vitrella brassicaformis, a Recently
      Discovered Chromerid: Comparison to Chromera velia and Phylogenetic Relationship
      with Apicomplexan Parasites.
AB  - Vitrella brassicaformis is the second discovered species in the Chromerida, and
      first in the family Vitrellaceae. Chromera velia, the first discovered species,
      forms an independent photosynthetic lineage with V. brassicaformis, and both are
      closely related to peridinin-containing dinoflagellates and nonphotosynthetic
      apicomplexans; both also show phylogenetic closeness with red algal plastids. We
      have utilized gas chromatography/mass spectrometry to identify two free sterols,
      24-ethylcholest-5-en-3beta-ol, and a minor unknown sterol which appeared to be a
      C(28:4) compound. We have also used RNA Seq analysis to identify seven genes
      found in the nonmevalonate/methylerythritol pathway (MEP) for sterol
      biosynthesis. Subsequent genome analysis of V. brassicaformis showed the presence
      of two mevalonate (MVA) pathway genes, though the genes were not observed in the
      transcriptome analysis. Transcripts from four genes (dxr, ispf, ispd, and idi)
      were selected and translated into proteins to study the phylogenetic relationship
      of sterol biosynthesis in V. brassicaformis and C. velia to other groups of algae
      and apicomplexans. On the basis of our genomic and transcriptomic analyses, we
      hypothesize that the MEP pathway was the primary pathway that apicomplexans used
      for sterol biosynthesis before they lost their sterol biosynthesis ability,
      although contribution of the MVA pathway cannot be discounted.

PMID- 25996518
TI  - Xenotransplantation of uterine leiomyoma in Wistar rats: a pilot study.
AB  - OBJECTIVE: To evaluate whether xenografts derived from hysterectomized patients
      would implant successfully and lead to uterine leiomyoma in Wistar rats. STUDY
      DESIGN: This experimental study examined six female Wistar rats implanted with
      uterine leiomyoma obtained from patients who underwent hysterectomies at the
      gynecological surgery service of the HUUFMA. The rats were divided into two
      groups. Group I consisted of three rats in which the uterine leiomyoma had been
      implanted in the parietal peritoneum, and group II consisted of three rats in
      which the uterine leiomyoma was implanted in the subcutaneous tissue. The
      immunosuppressant mycophenolate mofetil (MMF) was administered orally by gavage
      (at a dose of 40 mg/kg of body weight) to prevent transplant rejection starting
      15 days before the transplant and continuing throughout the entire experiment.
      After four weeks, necrosis and neovascularization were evaluated histologically
      in both groups and were classified as either absent or present. Lymphocytic
      inflammatory infiltration was also examined and classified as mild, moderate or
      intense (by hematoxylin and eosin staining), and fibrosis was classified as grade
      I-III (by Masson's trichrome staining). RESULTS: Necrosis was absent from all
      three rats in group I and was observed in only one rat from group II.
      Neovascularization was present in two rats from group I and in only one rat from
      group II. The lymphocytic inflammatory infiltrate was mild in two rats and
      moderate in one rat from group I, and it was moderate in two rats and intense in
      one rat from group II. Two rats from group 1 exhibited grade III fibrosis, and
      one rat presented grade I fibrosis. In group II, two rats presented grade I
      fibrosis and one rat had grade II fibrosis. When necrosis and neovascularization
      were evaluated as variables, group I demonstrated greater evidence of successful
      implantation when compared to group II, indicating that the peritoneal
      implantation technique produces better results than the subcutaneous approach
      (p=0.039). CONCLUSION: This study demonstrates that the xenotransplantation of
      uterine leiomyoma into the parietal peritoneum is more effective than the
      xenotransplantation of uterine leiomyoma into the subcutaneous tissue, and it
      describes a promising new model for the study of leiomyoma in vivo.

PMID- 25996520
TI  - Extracting body image symptom dimensions among eating disorder patients: the
      Profile Analysis via Multidimensional Scaling (PAMS) approach.
AB  - The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a
      procedure for extracting dimensions, in order to identify core eating disorder
      symptoms in a clinical sample. A large sample of patients with eating disorders
      (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI
      2; Garner, 1991), and PAMS was then employed to estimate individual profile
      weights that reflect the degree to which an individual's observed symptom profile
      approximates the pattern of the dimensions. The findings revealed three symptom
      dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent
      analysis using individual level data illustrate that the PAMS profiles properly
      operate as prototypical profiles that encapsulate all individuals' response
      patterns. The implications of these dimensional findings for the assessment and
      diagnosis of eating disorders are discussed. 

PMID- 25996521
TI  - Thermal resistance of Saccharomyces yeast ascospores in beers.
AB  - The industrial production of beer ends with a process of thermal pasteurization.
      Saccharomyces cerevisiae and Saccharomyces pastorianus are yeasts used to produce
      top and bottom fermenting beers, respectively. In this research, first the
      sporulation rate of 12 Saccharomyces strains was studied. Then, the thermal
      resistance of ascospores of three S. cerevisiae strains (DSMZ 1848, DSMZ 70487,
      Ethanol Red((r))) and one strain of S. pastorianus (ATCC 9080) was determined in
      4% (v/v) ethanol lager beer. D60  degrees C-values of 11.2, 7.5, 4.6, and 6.0 min
      and z-values of 11.7, 14.3, 12.4, and 12.7  degrees C were determined for DSMZ
      1848, DSMZ 70487, ATCC 9080, and Ethanol Red((r)), respectively. Lastly,
      experiments with 0 and 7% (v/v) beers were carried out to investigate the effect
      of ethanol content on the thermal resistance of S. cerevisiae (DSMZ 1848). D55 
      degrees C-values of 34.2 and 15.3 min were obtained for 0 and 7% beers,
      respectively, indicating lower thermal resistance in the more alcoholic beer.
      These results demonstrate similar spore thermal resistance for different
      Saccharomyces strains and will assist in the design of appropriate thermal
      pasteurization conditions for preserving beers with different alcohol contents.

PMID- 25996522
TI  - Report of postharvest rot of kiwifruit in Korea caused by Sclerotinia
      sclerotiorum.
AB  - In May 2014, sclerotinia rot symptoms caused by Sclerotinia sclerotiorum were
      observed on stored kiwifruit in Jinju, South Korea. The symptoms appeared as
      soft, water-soaked lesions on fruit covered with a white mycelium. The
      morphological characteristics and the internal transcribed spacer sequences of
      rRNA of the pathogen isolated from the sclerotinia rot showed it to be S.
      sclerotiorum. This was confirmed by performing a pathogenicity test with pure
      cultures of S. sclerotiorum and by reisolating S. sclerotiorum from artificially
      inoculated kiwifruits. Our results should help promote a better understanding of
      the diseases that affect kiwifruit and improve practices for postharvest disease
      control in the kiwifruit industry. 

PMID- 25996523
TI  - Hepatic oxidative stress biomarker responses in freshwater fish Carassius auratus
      exposed to four benzophenone UV filters.
AB  - Benzophenone (BP) type UV filters are widely used in many personal care products
      to protect human from UV irradiation. Despite the estrogenic potencies to fish
      and the environmental occurrences of BP derivatives in aquatic systems, little
      information is available regarding their effects on the antioxidant defense
      system in fish. In this work, the oxidative stress induced in livers of Carassius
      auratus was assessed using four biomarkers. The integrated biomarker response
      (IBR) was applied to assess the overall antioxidant status in fish. Moreover,
      liver tissues were also studied histologically. The changes in the activities of
      antioxidant enzymes and glutathione levels suggested that BPs generates oxidative
      stress in fish. The IBR index revealed that the hepatic oxidative toxicity
      followed the order BP-1>BP-2>BP-4>BP-3. The histopathological analysis revealed
      lesions caused by BPs. This investigation provides essential information for
      assessing the potential ecological risk of BP-type UV filters. 

PMID- 25996525
TI  - Reduction in toxicity of wastewater from three wastewater treatment plants to
      alga (Scenedesmus obliquus) in northeast China.
AB  - The toxicity of municipal wastewater to the receiving water bodies is still
      unknown, due to the lack of regulated toxicity based index for wastewater
      discharge in China. Our study aims at gaining insight into the acute toxic
      effects of local municipal wastewater on alga, Scenedesmus obliquus. Four
      endpoints, i.e. cell density, chlorophyll-A concentration, superoxide dismutase
      (SOD) activity and cell membrane integrity, of alga were analyzed to characterize
      the acute toxicity effects of wastewater from municipal wastewater treatment
      plants (WWTPs) with different treatment techniques: sequencing batch reactor
      (SBR), Linpor and conventional activated sludge. Influent and effluent from each
      treatment stage in these three WWTPs were sampled and evaluated for their acute
      toxicity. Our results showed that all three techniques can completely affect the
      algal chlorophyll-A synthesis stimulation effects of influent; the algal cell
      growth stimulation effect was only completely removed by the secondary treatment
      process in conventional activated sludge technique; toxic effects on cell
      membrane integrity of two influents from WWTPs with SBR and conventional
      activated sludge techniques were completely removed; the acute toxicity on SOD
      activity was partially reduced in SBR and conventional activated sludge
      techniques while not significantly reduced by Linpor system. As to the
      disinfection unit, NaClO disinfection enhanced wastewater toxicity dramatically
      while UV radiation had no remarkable influence on wastewater toxicity. Our
      results illustrated that SOD activity and chlorophyll-A synthesis were relatively
      sensitive to municipal wastewater toxicity. Our results would aid to understand
      the acute toxicity of municipal wastewater, as well as the toxicity removal by
      currently utilized treatment techniques in China. 

PMID- 25996524
TI  - Evaluation of ecotoxicological effects of drugs on Daphnia magna using different
      enzymatic biomarkers.
AB  - The increasing occurrence of pharmaceutical drugs in the aquatic environment is
      cause of concern, due to the possibility of toxic phenomena in non-target
      species, including oxidative stress and neurotoxicity. The present study aimed to
      assess the acute effect of four widely used therapeutic agents: acetaminophen
      (analgesic), chlorpromazine (antipsychotic), diclofenac (anti-inflammatory) and
      propranolol (antihypertensive), in the cladoceran species Daphnia magna.
      Considering the involvement of the mentioned compounds in the impairment of
      cholinesterasic activity and modifications in cellular redox systems, the purpose
      of this study was to analyze their effects on biomarkers of neuronal regulation,
      such as total cholinesterases (ChEs), and enzymatic oxidative stress defense,
      including as catalase (CAT), glutathione-S-transferases (GSTs), and total and
      selenium-dependent glutathione-peroxidase (total GPx; Se-GPx) activities.
      Exposure to acetaminophen caused a significant inhibition of AChE and Se-GPx
      activities in D. magna relative to the control. Among the biomarkers of oxidative
      stress, only the activity of CAT was significantly altered in concentration of
      0.001mg L(-1) of chlorpromazine, which was not always consistent with the
      literature. Diclofenac caused a significant inhibition of AChE and Se-dependent
      GPx, and also in total GPx activities. Propranolol was responsible for a
      significant decrease in the activity of the latter two enzymes, and also a slight
      increase of GSTs activity. The results indicated that the exposure to all the
      tested compounds induced alterations on the cellular redox status in the studied
      species. In addition, acetaminophen and diclofenac were shown to have the
      capability of interfering with D. magna neurotransmission, through the inhibition
      of ChEs. Our data enlighten the need for more research on the ecological
      consequences of pharmaceuticals in non-target organisms. 

PMID- 25996526
TI  - Trichuris suis soluble products induce Rab7b expression and limit TLR4 responses
      in human dendritic cells.
AB  - Inflammatory immune disorders such as inflammatory bowel disease and multiple
      sclerosis are major health problems. Currently, the intestinal whipworm Trichuris
      suis is being explored in clinical trials to reduce inflammation in these
      diseases; however, the mechanisms by which the parasite affects the host immune
      system are not known. Here we determined the effects of T. suis soluble products
      (SPs) on Toll-like receptor-4 (TLR4)-stimulated human dendritic cells (DCs) using
      Illumina bead chip gene arrays. Pathway analysis of lipopolysaccharide-stimulated
      DCs with or without T. suis treatment showed that co-stimulation with T. suis SPs
      resulted in a downregulation of both the myeloid differentiation primary response
      gene 88-dependent and the TIR-domain-containing adaptor-inducing interferon-beta
      dependent signalling pathways triggered by TLR4. These data were verified using
      quantitative real-time PCR of several key genes within these pathways and/or
      defining their protein levels. In addition, T. suis SPs induce Rab7b, a negative
      regulator of TLR4 signalling that interferes with its trafficking, which
      coincided with a reduced surface expression of TLR4. These data indicate that the
      mechanism by which T. suis SPs reduce inflammatory responses is through
      suppression of both TLR4 signalling and surface expression on DCs. 

PMID- 25996527
TI  - Determination of the structure of the O-antigen and the lipid A from the
      entomopathogenic bacterium Pseudomonas entomophila lipopolysaccharide along with
      its immunological properties.
AB  - The structure and the immunology of the lipopolysaccharide (LPS) of Pseudomonas
      entomophila, an entomopathogenic bacterium isolated from the fruit fly Drosophila
      melanogaster, was characterized. The O-antigen portion was established and
      resulted to be built up of a repetitive unit constituted by four monosaccharide
      residues, all L configured, all deoxy at C-6 and with an acetamido function at C
      2: ->3)-alpha-l-FucNAc-(1->4)-alpha-l-FucNAc-(1->3)-alpha-l-FucNAc-(1->3)-beta-l
      QuiNAc-(1-> The structural analysis of lipid A, showed a mixture of different
      species. The diphosphorylated glucosamine backbone carries six fatty acids
      consistent with the composition C10:0 3(OH), C12:0 2(OH) and C12:0 3(OH), whereas
      other species differs by the number of phosphates and/or of fatty acids. The
      immunology experiments demonstrated that the LPS structure of P. entomophila
      displayed a low ability to engage the TLR4-mediated signaling correlated to a
      significant antagonistic activity toward hexa-acylated LPS structures. 

PMID- 25996528
TI  - The Well-Being of Australian Service Mothers.
AB  - In recent years servicewomen with dependent children have for the first time in
      history been deployed into conflict zones in support of Australian Defence Force
      operations. This represents a significant social change, and the implications of
      deployment on the health of these service mothers are not fully understood. Data
      from women who participated in the Middle East Area of Operations Census study
      were analyzed to compare the psychological and physical symptoms reported by
      service mothers with service women who had no dependent children at the time of
      deploying to Afghanistan and/or Iraq. Of the 921 women who were included in this
      analysis, 235 had dependent children and 686 had no dependent children
      (comparison group). Service mothers were significantly older and were more likely
      to have served in the Air Force than women in the comparison group. Findings
      demonstrate that serving mothers were not at any significantly higher risk of
      psychological distress, post-traumatic stress symptoms, alcohol misuse, or
      reporting of somatic symptoms, than women who had no dependent children. A number
      of possible explanations for these findings are discussed, including the healthy
      soldier/mother effect, support from partners and extended family members, and
      collegial networks. 

PMID- 25996531
TI  - Are we doing well or oversizing follow-up in ovarian cancer? Searching for
      tailoring.

PMID- 25996529
TI  - Effects of contrast inversion on face perception depend on gaze location:
      Evidence from the N170 component.
AB  - Face recognition is known to be impaired when the contrast polarity of the eyes
      is inverted. We studied how contrast affects early perceptual face processing by
      measuring the face-sensitive N170 component to face images when the contrast of
      the eyes and of the rest of the face was independently manipulated. Fixation was
      either located on the eye region or on the lower part of a face. Contrast
      reversal of the eyes triggered delayed and enhanced N170 components independently
      of the contrast of other face parts, and regardless of gaze location. Similar
      N170 modulations were observed when the rest of a face was contrast-inverted, but
      only when gaze was directed away from the eyes. Results demonstrate that the
      contrast of the eyes and of other face parts can both affect face perception, but
      that the contrast polarity of the eye region has a privileged role during early
      stages of face processing.

PMID- 25996532
TI  - Low Back Pain: A Biomechanical Rationale Based on "Patterns" of Disc
      Degeneration.
AB  - STUDY DESIGN: A nonlinear finite element study of a lumbar spine with different
      "patterns" of multilevel intervertebral disc degeneration. OBJECTIVE: To
      determine how different patterns of multilevel disc degeneration influence the
      biomechanical behavior of the lumbar spine. SUMMARY OF BACKGROUND DATA: Because
      of the complex etiology of low back pain, it is often difficult to identify the
      specific factors that contribute to the symptoms of a particular patient. Disc
      degeneration is associated with the development of low back pain, but its
      presence is not always synonymous with symptoms. However, studies have suggested
      that "patterns" of disc degeneration may provide insight into such pain
      generation rather than the overall presence of degenerative changes.
      Specifically, individuals with contiguous multilevel disc degeneration have been
      shown to exhibit higher presence and severity of low back pain than patients with
      skipped-level disc degeneration (i.e., healthy discs located in between
      degenerated discs). METHODS: In this study, the biomechanical differences between
      these patterns were analyzed using a nonlinear finite element model of the lumbar
      spine. Thirteen separate "patterns" of disc degeneration were evaluated using the
      model and simulated under normal physiological loading conditions in each of the
      primary modes of spinal motion. RESULTS: The results showed that stresses and
      forces of the surrounding ligaments, facets, and pedicles at certain vertebral
      levels of the spine were generally lower in skipped-level disc degeneration cases
      than in the contiguous multilevel disc degenerations cases even when the skipped
      level contained more degenerated discs. CONCLUSION: To our knowledge, this is the
      first study to illustrate the biomechanics of specific patterns of disc
      degeneration of the lumbar spine. Using a multilevel disc degeneration model, our
      study provides insights as to why various patterns of disc degeneration
      throughout the lumbar spine may affect motion and soft tissue structures as well
      that may have bearing in the clinical pathway of pain generation. LEVEL OF
      EVIDENCE: N/A.

PMID- 25996533
TI  - Minimum 20 Years Long-term Clinical Outcome After Spinal Fusion and
      Instrumentation for Scoliosis: Comparison of the SRS-22 Patient Questionnaire
      With That in Nonscoliosis Group.
AB  - STUDY DESIGN: A retrospective minimum 20-year follow-up study using 4 standard
      self-administered questionnaires, one of which, the SRS-22 was also administered
      to control groups. OBJECTIVE: To evaluate long-term postoperative pain and other
      clinical outcomes of scoliosis correction and fusion surgery with Harrington
      instrumentation using Moe square-ended rods for better preservation of sagittal
      alignment. SUMMARY OF BACKGROUND DATA: Only a few long-term outcome studies have
      used standardized and validated self-administered tools, and no studies have
      established SRS-22 control data within their own population. There is no previous
      minimum 20-year follow-up evaluation after correction surgery preserving thoracic
      kyphosis and lumbar lordosis. METHODS: Of 86 consecutive patients who underwent
      instrumentation surgery for scoliosis by a single surgeon, 61 patients
      participated using Japanese Orthopaedic Association, Roland-Morris Disability
      Questionnaire, Oswestry Disability Index, and Scoliosis Research Society (SRS-22)
      questionnaires and 51 patients were included in this study. Results were analyzed
      for pain and other clinical outcomes. A total of 771 hospital employees were sent
      SRS-22 questionnaires. A total of 763 responded, resulting in 2 control groups
      composed of nonscoliosis and untreated mild scoliosis controls of the same
      culture and language as the long-term follow-up group. RESULTS: The prevalence of
      continuous low back pain was about 15%. Average Japanese Orthopaedic Association,
      Oswestry Disability Index, and Roland-Morris Disability Questionnaire scores at
      follow-up were 25 points, 7.3%, and 1.6, respectively. The average SRS-22 scores
      were 4.2 (function), 4.3 (pain), 3.7 (self-image), and 3.9 (mental health) for
      the postoperative follow-up group compared with 4.5 (function), 4.3 (pain), 3.5
      (self-image), and 3.5 (mental health) for the nonscoliosis controls. CONCLUSION:
      Improved preservation of normal sagittal alignment resulted in a prevalence of
      low back pain comparable with the age-matched general population. Moreover, SRS
      22 results for self-image and mental health were positive compared with the
      controls, possibly reflecting the surgeon's emphases on mental health and
      management of patient expectations. LEVEL OF EVIDENCE: 4.

PMID- 25996534
TI  - Epidural Steroids After a Percutaneous Endoscopic Lumbar Discectomy.
AB  - STUDY DESIGN: Randomized controlled study from a single surgeon. OBJECTIVE: The
      objective of the present study is to assess the effectiveness of the
      administration of epidural steroids in patients who undergo a percutaneous
      endoscopic lumbar discectomy (PELD) because of a herniated lumbar disc. SUMMARY
      OF BACKGROUND DATA: Steroids are drugs that show strong anti-inflammatory
      effects; in specific, the effects of epidural steroid application after an open
      lumbar discectomy have been studied extensively. However, no study has been
      conducted on the effects of perioperative epidural steroids after PELD. METHODS:
      One hundred patients who had undergone a PELD because of a herniated lumbar disc
      were randomized into 2 groups. Patients in group 1 were subjected to an epidural
      steroid application after a PELD, whereas patients in group 2 were treated with
      saline after a PELD. RESULTS: There was a significant decrease in visual analogue
      scale (VAS) scores (back, leg) and Oswestry Disability Index at all examinations
      (P < 0.01). When comparing the 2 groups, group 1 showed lower levels of VAS
      scores (back) in all examinations than group 2 but was not statistically
      significant (P = 0.257). In VAS score (leg), group 1 showed a significant
      decrease compared with the group 2 at 1 and 4 weeks of follow-up examination (P =
      0.020, P = 0.032). In Oswestry Disability Index, group 1 showed a significant
      decrease compared with the group 2 at 1-week follow-up examination (P < 0.01).The
      mean hospital stay was statistically significantly shorter in group 1 (P < 0.01).
      The mean periods before returning to work for those who returned to work in group
      1 and group 2 were 4.45 +/- 3.59 weeks and 6.48 +/- 4.88 weeks, respectively,
      when measured at follow-up at 6 months; the period in group 1 was statistically
      significantly shorter (P = 0.024). CONCLUSION: Epidural steroids after a PELD
      reduce back pain and leg pain while improving functional outcomes in the short
      term postsurgery period. LEVEL OF EVIDENCE: 2.

PMID- 25996535
TI  - Descriptive Epidemiology of Spinal Meningiomas in the United States.
AB  - STUDY DESIGN: Cross-sectional study of US cancer registry data. OBJECTIVE: To
      present the current population-based descriptive epidemiology of spinal
      meningiomas in the United States. SUMMARY OF BACKGROUND DATA: Meningioma is the
      most common primary spinal tumor, yet there is a paucity of population-based data
      evaluating incidence according to age, sex, race, and ethnicity. Such data are
      necessary to assess the burden of spinal meningiomas on varying populations and
      to inform health care planning and future research. METHODS: The Central Brain
      Tumor Registry of the United States, which contains the largest aggregation of
      population-based data on the incidence of primary central nervous system tumors
      in the United States, was used. Age-adjusted incidence rates of spinal
      meningiomas from 2004 to 2010 were calculated by age at diagnosis, sex, race, and
      ethnicity. Annual percent change was calculated using Joinpoint to characterize
      temporal trends. RESULTS: From 2004 to 2010, there were 7148 newly diagnosed
      spinal meningiomas, resulting in an overall age-adjusted incidence of 0.33 per
      100,000 population. There was a nonsignificant increase in incidence over time
      (annual percent change: 0.8%, 95% confidence interval: -1.4 to 3.0). The highest
      incidence occurred in the 75- to 84-year old age group. Females had a much higher
      incidence than males (incidence rate ratio: 3.37; P < 0.0001). Asian Pacific
      Islanders and Caucasians had the highest incidence. Compared with Caucasians,
      African Americans and American Indian/Alaskan Native individuals had a
      significantly lower incidence (incidence rate ratio: 0.72, P < 0.0001; 0.52, P =
      0.0003, respectively). Non-Hispanics had a significantly lower incidence than
      Hispanics (incidence rate ratio: 0.81, P < 0.0001). CONCLUSION: Approximately
      1000 spinal meningiomas were diagnosed in the United States per year, and the
      incidence was relatively stable. Advanced age, female sex, Asian Pacific Islander
      and Caucasian race, and Hispanic ethnicity were all associated with an increased
      incidence of spinal meningioma. This study represents the most comprehensive
      evaluation of population-based descriptive epidemiology of spinal meningiomas in
      the United States to date. LEVEL OF EVIDENCE: 2.

PMID- 25996536
TI  - Cost-effectiveness of Lumbar Epidural Steroid Injections.
AB  - STUDY DESIGN: Longitudinal cohort. OBJECTIVE: To determine the cost per quality
      adjusted life-year for lumbar epidural steroid injections (LESI). SUMMARY OF
      BACKGROUND DATA: Despite being a widely performed procedure, there are few
      studies evaluating the cost-effectiveness of LESIs. METHODS: Patients who had
      received LESI between June 2012 and July 2013 with EuroQOL-5D (EQ-5D) scores
      available before and after LESIs but before any surgical intervention were
      identified. Costs were calculated on the basis of the Medicare Fee Schedule
      multiplied by the number of LESIs received between the 2 clinic visits. Quality
      adjusted life-years (QALYs) were calculated using the EQ-5D. RESULTS: Of 421
      patients who had pre-LESI EQ-5D data, 323 (77%) had post-LESI data available; 200
      females, 123 males, mean age: 59.2 +/- 14.2 years. Cost per LESI was $608, with
      most patients receiving 3 LESIs for more than 1 year (range: 1-6 yr). Mean QALY
      gained was 0.005. One hundred forty-five patients (45%) had a QALY gain (mean =
      0.117) at a cost of $62,175 per QALY gained; 127 patients (40%) had a loss in
      QALY (mean = -0.120) and 51 patients (15%) had no change in QALY. Fourteen of the
      145 patients who improved, and 29 of the 178 patients who did not, have medical
      comorbidities that precluded surgery. Thirty-two (22%) of 131 patients without
      medical comorbidities who improved and 57 (32%) of 149 patients without medical
      comorbidities who did not improve subsequently had undergone surgery (P = 0.015).
      CONCLUSION: LESI may not be cost-effective in patients with lumbar degenerative
      disorders. For the 145 patients who improved, cost per QALY gained was acceptable
      at $62,175. However, for the 178 patients with no gain or a loss in QALY, the
      economics are not reportable with a cost per QALY gained being theoretically
      infinite. Further studies are needed to identify specific patient populations who
      will benefit from LESI because the economic viability of LESI requires improved
      patient selection. LEVEL OF EVIDENCE: 2.

PMID- 25996537
TI  - Trajectories of symptoms and function in older adults with low back disorders.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To determine whether there are
      distinct trajectories of back pain and function among older adults and to
      identify characteristics that distinguish among patients with substantially
      different prognoses. SUMMARY OF BACKGROUND DATA: Although the differential
      diagnosis and course of low back pain among older adults may differ from middle
      aged adults, there is little evidence. Better understanding variability in
      recovery among older adults may help target patients for more intensive clinical
      interventions, plan resource use, and design clinical studies of more homogeneous
      patient groups. METHODS: Patients aged 65 years or older with a new episode of
      care for back pain were recruited at 3 geographically diverse sites. Patients
      completed pain intensity and Roland-Morris Disability measures at baseline and 3,
      6, and 12 months later. We used latent class analysis to identify distinct
      trajectories of pain and function and then logistic regression to identify
      predictors of membership in the improving trajectories. RESULTS: There were 3929
      participants who completed outcome measures at every follow-up interval. Latent
      class analysis identified subgroups with low, intermediate, or high pain or
      disability scores who remained relatively stable over time. However, small
      subgroups showed dramatic improvement from baseline to 1 year (17% with major
      improvement in Roland score, pain intensity, or both). Shorter pain duration,
      higher patient confidence in improvement, and fewer comorbid conditions at
      baseline were each associated independently with favorable prognosis. CONCLUSION:
      Although most patients remained relatively stable over a year, latent class
      analysis identified small groups with major improvement in pain, function, or
      both. This technique may, therefore, be useful for studying back pain prognosis.
      Our results should help assemble more prognostically homogeneous groups for
      research, and the technique may help identify subgroups of patients with uniquely
      successful responses to investigational interventions. LEVEL OF EVIDENCE: 3.

PMID- 25996538
TI  - Postoperative Narcotic Consumption in Workman's Compensation Patients Following a
      Minimally Invasive Transforaminal Lumbar Interbody Fusion.
AB  - STUDY DESIGN: Retrospective cohort analysis of a prospective registry. OBJECTIVE:
      To assess the differences in perioperative narcotic consumption between Workman's
      compensation (WC) and non-Workman's compensation (non-WC) patients after a single
      level minimally invasive transforaminal lumbar interbody fusion. SUMMARY OF
      BACKGROUND DATA: There is concern regarding the potential overutilization of
      opioid pain medication in WC patients. However, the impact of WC status on
      perioperative narcotic consumption after lumbar spine procedures has not been
      previously reported. METHODS: A cohort of patients who underwent primary 1-level
      minimally invasive transforaminal lumbar interbody fusion procedures for
      degenerative spinal pathology between 2007 and 2013 was retrospectively analyzed
      using a prospectively collected registry. First, preoperative and perioperative
      characteristics were compared between WC and non-WC patients. Second, mean oral
      morphine equivalent was compared between WC and non-WC patients with adjustment
      for any preoperative or perioperative differences between cohorts. RESULTS: A
      total of 136 single-level, primary minimally invasive-transforaminal lumbar
      interbody fusion procedures were included in the analysis, of which 46 (33.8%)
      were WC patients. WC patients were younger (47.8 +/- 11.2 vs. 57.9 +/- 10.4 yr; P
      < 0.001) and had a lower comorbidity burden (Charlson Comorbidity Index: 1.85 +/-
      1.30 vs. 3.42 +/- 2.07; P < 0.001) than non-WC patients. The distribution of
      ethnicity differed between WC and non-WC patients (P = 0.002). WC patients
      incurred longer procedural times (135.2 +/- 52.2 vs. 118.9 +/- 33.7 min; P <
      0.05). However, the estimated blood loss, length of hospital stay, and day of
      discharge were no different between WC and non-WC patients. Mean oral morphine
      equivalent consumption did not differ between WC and non-WC patients after
      adjustment for differences in age, ethnicity, Charlson Comorbidity Index, and
      procedural time between cohorts. CONCLUSION: Despite concerns for greater opioid
      use in the WC population, this analysis demonstrated similar total narcotic
      consumption between WC and non-WC patients during the immediate postoperative
      period. Long-term studies are warranted to assess whether this similarity in
      regard to perioperative narcotic consumption persists beyond the immediate
      postoperative period. LEVEL OF EVIDENCE: 3.

PMID- 25996539
TI  - How Safe Is High-Speed Burring in Spine Surgery? An In Vitro Study on the Effect
      of Rotational Speed and Heat Generation in the Bovine Spine.
AB  - STUDY DESIGN: In vitro animal cadaveric study. OBJECTIVE: To identify the
      appropriate rotational speed and safe bone distance from neural tissue during
      bone burring in spinal surgery. SUMMARY OF BACKGROUND DATA: Bone burring is a
      common step in spinal surgery. Unwanted frictional heat produced during bone
      burring may result in thermal injury to the bone and adjacent neural structure.
      One of the important parameters influencing the bone temperature rise during bone
      burring is rotational speed. METHODS: This laboratory-based animal study used
      bovine spine bones, and the tests were conducted using a steel round burr. The
      bone temperature was measured simultaneously with thermocouple at the distances
      of 1 mm, 3 mm, and 5 mm from the burring site during the burring process. The
      bone burring was done with 4 different rotational speeds of 35,000 revolutions
      per minute (rpm), 45,000 rpm, 65,000 rpm, and 75,000 rpm. RESULTS: This study
      showed that increasing the rotational speed significantly elevated bone
      temperature. The threshold temperature of 47 degrees C was reached when bone was
      burred for 10 seconds, with a rotational speed of 45,000 rpm. The mean bone
      temperature measured at a distance 1 mm from the burring site for all 4
      rotational speeds was always higher than that measured at a distance of 3 mm and
      5 mm and this difference was statistically significant (P < 0.001). There was no
      significant difference between the mean bone temperature measured at a distance
      of 3 mm and 5 mm (P > 0.05). CONCLUSION: Taking 47 degrees C as the threshold
      temperature for causing significant impairment to the regenerative capacity of
      bone, a rotational speed of lower than 45,000 rpm is preferable so as to minimize
      thermal injury to bone tissue. We also concluded that a 3-mm distance between the
      site of burring and the neural tissue is a safe distance. LEVEL OF EVIDENCE: N/A.

PMID- 25996540
TI  - Association Between Surgeon Experience and Complication Rates in Adult Scoliosis
      Surgery: A Review of 5117 Cases From the Scoliosis Research Society Database 2004
      2007.
AB  - STUDY DESIGN: Retrospective review of a multicenter database. OBJECTIVE: To
      evaluate whether surgeon experience is associated with complication rates in
      adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: Multiple
      patient- and surgery-related factors have been shown to increase the risk of
      complications in ASD. No study exists evaluating surgeon experience as an
      associated factor with complications in ASD. METHODS: The Scoliosis Research
      Society Morbidity and Mortality database was queried for patients older than 18
      years who underwent ASD from 2004 to 2007. Patient demographics, surgical
      characteristics, complications, and surgeon membership status were analyzed. Two
      tailed t test and chi tests were performed, with P value of less than 0.05
      considered significant. RESULTS: A total of 5117 patients underwent ASD surgery.
      The average patient age was 51.8 years. Patients operated by candidate members
      were older than those operated by active members (53.1 vs. 51.4, P = 0.003).
      Active members performed 3836 (75%) cases whereas candidate members performed
      1281 cases. There were 1110 (21.7%) revisions. A total of 681 (13.3%)
      complications were recorded, 498 (13.0%) for active and 183 (14.3%) for candidate
      members, respectively (P = 0.24). Mortality rate was 0.29%. Spinal cord
      complications accounted for 0.68% of all cases. Active members had 21 (0.55%)
      spinal cord complications, whereas candidates had 14 (1.1%) (P = 0.049). There
      were a total of 174 (3.4%) surgical site infections (SSI). Active members had 82
      (2.1%) deep SSI, whereas candidate members had 36 (2.8%) deep SSI (P = 0.164).
      Active members had 33 (0.9%) superficial SSI whereas candidate members had 23
      (1.8%) superficial SSI (P = 0.008). CONCLUSION: There was a statistically
      significant, 2-fold increase in the rate of spinal cord complications and
      superficial SSI among candidate compared with active members. Overall
      complication rates were similar between candidate and active members. LEVEL OF
      EVIDENCE: 4.

PMID- 25996541
TI  - Hybrid Technique for Cervical Pedicle Screw Placement: Combination of Miniopen
      Surgery and Use of a Percutaneous Cannula System-Pilot Study.
AB  - STUDY DESIGN: Cadaver study and clinical application; a pilot study. OBJECTIVE:
      To minimize muscle dissection and enhance accuracy of cervical pedicle screw
      (CPS) placement by using a percutaneous cannula system. SUMMARY OF BACKGROUND
      DATA: Many studies have reported that the most frequent misplacement of CPSs is
      breach of the lateral wall; thus, an easy technique for securing medial
      convergence is required. We developed a percutaneous cannula system for this
      purpose and report the results of a cadaver study and its clinical application.
      METHODS: A cadaver study was conducted to confirm the possibility of this
      percutaneous technique in 5 specimens (50 CPSs, C3-C7). Then, the technique was
      applied in 8 patients (40 CPSs, C3-C7). The surgical technique was a hybrid of
      miniopen surgery and the use of percutaneous cannula system under lateral
      fluoroscopic guidance. Entry holes were made in the open field and a cannula was
      used for tapping and insertion of CPSs. A stiff pedicle probe through the cannula
      was used to locate the pedicle in the lateral mass. RESULTS: In the cadaver
      study, there were 12 (24%) misplacements among 50 CPSs used. The hybrid technique
      was applied clinically in 4 traumatic, 2 degenerative, and 2 failed back surgery
      lesions. Thirty CPSs were inserted using the percutaneous cannula system and 10
      were inserted using a cannula as a retractor. Misplacement occurred in 6.7% (n =
      2) and 20% (n = 2) pedicles, respectively, and there were no symptomatic
      complications (total incidence, 10%). An additional incision for the cannula
      system can be made for 2-level CPS insertions. CONCLUSION: Use of the
      percutaneous cannula system facilitated a secure convergence angle for CPS
      insertion without extending muscle dissection or shifting cervical alignment
      because of muscle retraction. Moreover, this system can be used for CPS insertion
      in bull-necked patients. LEVEL OF EVIDENCE: 3.

PMID- 25996544
TI  - Shared elements of host-targeting pathways among apicomplexan parasites of
      differing lifestyles.
AB  - Apicomplexans are a diverse group of obligate parasites occupying different
      intracellular niches that require modification to meet the needs of the parasite.
      To efficiently manipulate their environment, apicomplexans translocate numerous
      parasite proteins into the host cell. Whereas some parasites remain contained
      within a parasitophorous vacuole membrane (PVM) throughout their developmental
      cycle, others do not, a difference that affects the machinery needed for protein
      export. A signal-mediated pathway for protein export into the host cell has been
      characterized in Plasmodium parasites, which maintain the PVM. Here, we
      functionally demonstrate an analogous host-targeting pathway involving organellar
      staging prior to secretion in the related bovine parasite, Babesia bovis, a
      parasite that destroys the PVM shortly after invasion. Taking into account recent
      identification of a similar signal-mediated pathway in the coccidian parasite
      Toxoplasma gondii, we suggest a model in which this conserved pathway has evolved
      in multiple steps from signal-mediated trafficking to specific secretory
      organelles for controlled secretion to a complex protein translocation process
      across the PVM. 

PMID- 25996546
TI  - Th17 polarization and upper airways: new insights.

PMID- 25996545
TI  - Roles of small RNAs in the effects of nutrition on apoptosis and spermatogenesis
      in the adult testis.
AB  - We tested whether reductions in spermatozoal quality induced by under-nutrition
      are associated with increased germ cell apoptosis and disrupted spermatogenesis,
      and whether these effects are mediated by small RNAs. Groups of 8 male sheep were
      fed for a 10% increase or 10% decrease in body mass over 65 days. Underfeeding
      increased the number of apoptotic germ cells (P < 0.05) and increased the
      expression of apoptosis-related genes (P < 0.05) in testicular tissue. We
      identified 44 miRNAs and 35 putative piRNAs that were differentially expressed in
      well-fed and underfed males (FDR < 0.05). Some were related to reproductive
      system development, apoptosis (miRNAs), and sperm production and quality
      (piRNAs). Novel-miR-144 (miR-98), was found to target three apoptotic genes
      (TP53, CASP3, FASL). The proportion of miRNAs as a total of small RNAs was
      greater in well-fed males than in underfed males (P < 0.05) and was correlated (r
      = 0.8, P < 0.05) with the proportion of piRNAs in well-fed and underfed males. In
      conclusion, the reductions in spermatozoal quality induced by under-nutrition are
      caused, at least partly, by disruptions to Sertoli cell function and increased
      germ cell apoptosis, mediated by changes in the expression of miRNAs and piRNAs.

PMID- 25996547
TI  - Physiologically motivated multiplex Kuramoto model describes phase diagram of
      cortical activity.
AB  - We derive a two-layer multiplex Kuramoto model from Wilson-Cowan type
      physiological equations that describe neural activity on a network of
      interconnected cortical regions. This is mathematically possible due to the
      existence of a unique, stable limit cycle, weak coupling, and inhibitory synaptic
      time delays. We study the phase diagram of this model numerically as a function
      of the inter-regional connection strength that is related to cerebral blood flow,
      and a phase shift parameter that is associated with synaptic GABA concentrations.
      We find three macroscopic phases of cortical activity: background activity
      (unsynchronized oscillations), epileptiform activity (highly synchronized
      oscillations) and resting-state activity (synchronized clusters/chaotic
      behaviour). Previous network models could hitherto not explain the existence of
      all three phases. We further observe a shift of the average oscillation frequency
      towards lower values together with the appearance of coherent slow oscillations
      at the transition from resting-state to epileptiform activity. This observation
      is fully in line with experimental data and could explain the influence of
      GABAergic drugs both on gamma oscillations and epileptic states. Compared to
      previous models for gamma oscillations and resting-state activity, the multiplex
      Kuramoto model not only provides a unifying framework, but also has a direct
      connection to measurable physiological parameters. 

PMID- 25996548
TI  - Identification of ex-vivo confocal scanning microscopic features and their
      histological correlates in human skin.
AB  - Ex-vivo confocal laser scanning microscopy (CLSM) is an emerging diagnostic tool
      allowing fast and easy microscopic tissue examination. The first generation of ex
      vivo devices have already shown promising results in the ex-vivo evaluation of
      basal cell carcinoma compared to Mohs surgery. Nevertheless, for the diagnostics
      of pathological skin lesions the knowledge of normal skin features is essential.
      Therefore we examined 50 samples of healthy skin from various donor sites
      including head and neck (n = 25), trunk (n = 10), upper (n = 10) and lower
      extremities (n = 5) using a new generation ex-vivo CLSM device offering three
      different laser wavelengths and compared the findings to the corresponding
      histological sections. In correlation with the histopathology we identified
      different layers of the epidermis, differentiated keratinocytes from melanocytes
      and described in detail skin appendages including hair follicle, sebaceous and
      sweat glands. Furthermore, structures of the dermis and subcutis were
      illustrated. Additionally, artefacts and pitfalls occurring with the use of ex
      vivo CLSM have been documented. The study offers an overview of the main ex-vivo
      CLSM skin characteristics in comparison to the standard histological examination
      and helps to recognize and avoid common artefacts. Anatomy of a hair follicle in
      the reflectance mode (RM) CLSM, fluorescence mode (FM) CLSM and in a routine
      hematoxylin-eosin stained histological section (H). 

PMID- 25996549
TI  - Synthesis of 2-Arylpyridopyrimidinones, 6-Aryluracils, and Tri- and
      Tetrasubstituted Conjugated Alkenes via Pd-Catalyzed Enolic C-O Bond Activation
      Arylation.
AB  - A new and efficient approach for the synthesis of biologically important 2-aryl
      4H-pyrido[1,2-a]pyrimidin-4-ones and 6-aryluracils via previously unknown Pd
      catalyzed enolic C-OH activation-arylation of pyridopyrimidin-2,4-diones and
      barbituric acids, respectively, with boronic acids is reported. The starting
      materials are readily available, and products are obtained in high yields. An
      efficient and chemo- and stereoselective access to various tri- and
      tetrasubstituted conjugated alkenones and alkenoates is also obtained in this
      arylation approach. Interestingly, the procedure for the construction of such
      diverse molecular frameworks is general and featured with excellent substrates
      scope, tolerance of a broad range of functionalities, the unusual viability of
      performing the reaction under open air and in aqueous cosolvent, and the
      amenability to a scale-up synthesis, which have been found to be common
      limitations in the conventional/classical routes. The application of the protocol
      in a simple one-step high-yield route to pharmaceutically important polyarylated
      pyridopyrimidinone demonstrates its further synthetic utility. 

PMID- 25996550
TI  - The Hydric Effect in Inorganic Nanomaterials for Nanoelectronics and Energy
      Applications.
AB  - Protons, as one of the world's smallest ions, are able to trigger the charge
      effect without obvious lattice expansion inside inorganic materials, offering a
      unique and important test-bed for controlling their diverse functionalities.
      Arising from the high chemical reactivity of hydrogen (easily losing an electron)
      with various main group anions (easily accepting a proton), the hydric effect
      provides a convenient and environmentally benign route to bring about fascinating
      new physicochemical properties, as well as to create new inorganic structures
      based on the "old lattice" without dramatically destroying the pristine
      structure, covering most inorganic materials. Moreover, hydrogen atoms tend to
      bond with anions or to produce intrinsic defects, both of which are expected to
      inject extra electrons into lattice framework, promising advances in control of
      bandgap, spin behavior, and carrier concentration, which determine functionality
      for wide applications. In this review article, recently developed effective
      hydric strategies are highlighted, which include the conventional hydric reaction
      under high temperature or room temperature, proton irradiation or hydrogen plasma
      treatment, and gate-electrolyte-driven adsorption or doping. The diverse
      physicochemical properties brought by the hydric effect via modulation of the
      intrinsic electronic structure are also summarized, finding wide applications in
      nanoelectronics, energy applications, and catalysis. 

PMID- 25996551
TI  - Detection of undeclared animal by-products in commercial canine canned foods:
      Comparative analyses by ELISA and PCR-RFLP coupled with slab gel electrophoresis
      or capillary gel electrophoresis.
AB  - BACKGROUND: The potential presence of undeclared animal by-products in pet foods
      is not subject to routine examination. Previously published methods for species
      based identification of animal by-products have not been used routinely owing to
      inconsistent results. The present study evaluated the utility of several
      approaches for accurate identification of animal by-products in 11 commercial
      brands of canine canned foods. RESULTS: Canine canned foods from several
      countries were analysed by ELISA, PCR-RFLP coupled with slab-gel electrophoresis
      (SGE) and capillary gel electrophoresis (CGE) to test for evidence of by-products
      derived from cattle, chicken, sheep or pig. While CGE-based analysis detected all
      (24) animal-derived by-products that were reported for the 11 test samples, SGE
      and ELISA detected only 22/24 (92%) and 14/24 (58%) of labelled by-products,
      respectively. In addition, undeclared animal by-products were found using all
      three analytical approaches with CGE detecting more positives (19) than SGE (17)
      or ELISA (5). CONCLUSION: Significant disparities were evident between the
      labelled contents and the detected content of animal by-products. CGE-based
      testing for PCR products appears to provide greater sensitivity and accuracy than
      either SGE or ELISA-based methods. As testing of commercial products becomes more
      reliable and mainstream, manufacturers will need to develop more thorough and
      accurate labelling protocols.

PMID- 25996552
TI  - Development of a new dual polarity and viscosity probe based on the foldamer
      concept.
AB  - Small molecular probes able to act as sensors are of enormous interest thanks to
      their multiple applications. Here, we report on the development of a novel
      supramolecular dual viscosity and polarity probe based on the foldamer concept,
      which increases the resolution limits of traditional probes at low viscosity
      values (0-4 mPa.s). The applicability of this new probe has been tested with a
      supramolecular organogel. 

PMID- 25996554
TI  - Impact of Coordination Geometry, Bite Angle, and Trans Influence on Metal-Ligand
      Covalency in Phenyl-Substituted Phosphine Complexes of Ni and Pd.
AB  - Despite the long-standing use of phosphine and diphosphine ligands in
      coordination chemistry and catalysis, questions remain as to their effects on
      metal-ligand bonding in transition metal complexes. Here we report ligand K-edge
      XAS, DFT, and TDDFT studies aimed at quantifying the impact of coordination
      geometry, diphosphine bite angle, and phosphine trans influence on covalency in M
      P and M-Cl bonds. A series of four-coordinate NiCl2 and PdCl2 complexes
      containing PPh3 or Ph2P(CH2)nPPh2, where n = 1 (dppm), 2 (dppe), 3 (dppp), and 4
      (dppb), was analyzed. The XAS data revealed that changing the coordination
      geometry from tetrahedral in Ni(PPh3)2Cl2 (1) to square planar in Ni(dppe)Cl2 (2)
      more than doubles the intensity of pre-edge features assigned to Ni-P and Ni-Cl
      1s -> sigma* transitions. By way of comparison, varying the diphosphine in
      Pd(dppm)Cl2 (4), Pd(dppp)Cl2 (6), and Pd(dppb)Cl2 (7) yielded Pd-P 1s -> sigma*
      transitions with identical intensities, but a 10% increase was observed in the P
      K-edge XAS spectrum of Pd(dppe)Cl2 (5). A similar observation was made when
      comparing Ni(dppe)Cl2 (2) to Ni(dppp)Cl2 (3), and DFT and TDDFT calculations
      corroborated XAS results obtained for both series. Comparison of the
      spectroscopic and theoretical results to the diphosphine structures revealed that
      changes in M-P covalency were not correlated to changes in bite angles or
      coordination geometry. As a final measure, P and Cl K-edge XAS data were
      collected on trans-Pd(PPh3)2Cl2 (8) for comparison to the cis diphosphine complex
      Pd(dppe)Cl2 (5). Consistent with phosphine's stronger trans influence compared to
      chloride, a 35% decrease in the intensity of the Pd-P 1s -> sigma* pre-edge
      feature and a complementary 34% increase in Pd-Cl 1s -> sigma* feature was
      observed for 8 (trans) compared to 5 (cis). Overall, the results reveal how
      coordination geometry, ligand arrangement, and diphosphine structure affect
      covalent metal-phosphorus and metal-chloride bonding in these late transition
      metal complexes. 

PMID- 25996553
TI  - Design, synthesis and characterisation of new chimeric ruthenium(II)-gold(I)
      complexes as improved cytotoxic agents.
AB  - Two heterobimetallic complexes, i.e. [RuCl2(p-cymene)(MU-dppm)AuC] (1) and
      [RuCl2(p-cymene)(MU-dppm)Au(S-thiazoline)] (3), based on known cytotoxic [Ru(p
      cymene)Cl2(PR3)] and [AuX(PR3)] (X = Cl, SR) molecular scaffolds, with the
      diphosphane linker 1,1-bis(diphenylphosphino)methane, dppm, were conveniently
      prepared and characterised. Remarkably, the new compounds manifested a more
      favourable in vitro pharmacological profile toward cancer cells than individual
      ruthenium and gold species being either more cytotoxic or more selective. The
      interactions of the studied compounds with (pBR322) DNA and their inhibitory
      effects on cathepsin B were also assessed. In addition, their reactivity toward
      suitable models of protein targets was explored and clear evidence gained for
      disruption of the bimetallic motif and for protein binding of monometallic
      fragments. Overall, the data reported here strongly support the concept of
      multifunctional heterometallic compounds as "improved" candidate agents for
      cancer treatment. The mechanistic and pharmacological implications of the present
      findings are discussed. 

PMID- 25996555
TI  - Surface invasive cleavage assay on a maskless light-directed diamond DNA
      microarray for genome-wide human SNP mapping.
AB  - The surface invasive cleavage assay, because of its innate accuracy and ability
      for self-signal amplification, provides a potential route for the mapping of
      hundreds of thousands of human SNP sites. However, its performance on a high
      density DNA array has not yet been established, due to the unusual "hairpin"
      probe design on the microarray and the lack of chemical stability of commercially
      available substrates. Here we present an applicable method to implement a
      nanocrystalline diamond thin film as an alternative substrate for fabricating an
      addressable DNA array using maskless light-directed photochemistry, producing the
      most chemically stable and biocompatible system for genetic analysis and
      enzymatic reactions. The surface invasive cleavage reaction, followed by
      degenerated primer ligation and post-rolling circle amplification is
      consecutively performed on the addressable diamond DNA array, accurately mapping
      SNP sites from PCR-amplified human genomic target DNA. Furthermore, a specially
      designed DNA array containing dual probes in the same pixel is fabricated by
      following a reverse light-directed DNA synthesis protocol. This essentially
      enables us to decipher thousands of SNP alleles in a single-pot reaction by the
      simple addition of enzyme, target and reaction buffers. 

PMID- 25996556
TI  - Akt1 phosphorylates Nicastrin to regulate its protein stability and activity.
AB  - The gamma-secretase is a multiprotein complex that cleaves many type-I membrane
      proteins, such as the Notch receptor and the amyloid precursor protein. Nicastrin
      (NCT) is an essential component of the multimeric gamma-secretase complex and
      functions as a receptor for gamma-secretase substrates. In this study, we found
      that Akt1 markedly regulated the protein stability of NCT. Importantly, the
      kinase activity of Akt1 was essential for the inhibition of gamma-secretase
      activity through degradation of NCT. Notably, the protein level of endogenous NCT
      was higher in shAkt1-expressing cells than in shCon-expressing cells. Akt1
      physically interacted with NCT and mediated its degradation through proteasomal
      and lysosomal pathways. We also found that Akt1 phosphorylates NCT at Ser437,
      resulting in a significant reduction in NCT protein stability. Importantly, a
      phospho-deficient mutation in NCT at Ser437 stabilized its protein levels.
      Collectively, our results reveal that Akt1 functions as a negative regulator of
      the gamma-secretase activity through phosphorylation and degradation of NCT.
      Generation of the amyloid peptide (A-beta) and the amyloid precursor protein
      (APP) intracellular domain (AICD) can happen by sequential proteolysis of APP by
      beta and gamma-secretase. The gamma-secretase complex consists of four essential
      proteins: presenilin (PS1 or PS2), presenilin enhancer 2 (PEN-2), anterior
      pharynx-defective 1 (APH-1), and the Nicastrin (NCT). NCT can interact and be
      phosphorylated by Akt1, and phosphorylated NCT promotes its proteasomal and
      lysosomal degradation. As a result, Akt1 plays role in reducing gamma-secretase
      activity through phosphorylation-dependent regulation of NCT protein degradation.

PMID- 25996558
TI  - In reply.

PMID- 25996557
TI  - Outcomes in critically ill patients with systemic rheumatic disease: a
      multicenter study.
AB  - BACKGROUND: Patients with systemic rheumatic diseases (SRDs) may require ICU
      management for SRD exacerbation or treatment-related infections or toxicities.
      METHODS: This was an observational study at 10 university-affiliated ICUs in
      France. Consecutive patients with SRDs were included. Determinants of ICU
      mortality were identified through multivariable logistic analysis. RESULTS: Three
      hundred sixty-three patients (65.3% women; median age, 59 years [interquartile
      range, 42-70 years]) accounted for 381 admissions. Connective tissue disease
      (primarily systemic lupus erythematosus) accounted for 66.1% of SRDs and systemic
      vasculitides for 26.2% (chiefly antineutrophil cytoplasm antibodies-associated
      vasculitides). SRDs were newly diagnosed in 43 cases (11.3%). Direct admission to
      the ICU occurred in 143 cases (37.9%). Reasons for ICU admissions were infection
      (39.9%), SRD exacerbation (34.4%), toxicity (5.8%), or miscellaneous (19.9%).
      Respiratory involvement was the leading cause of admission (56.8%), followed by
      shock (41.5%) and acute kidney injury (42.2%). Median Sequential Organ Failure
      Assessment (SOFA) score on day 1 was 5 (3-8). Mechanical ventilation was required
      in 57% of cases, vasopressors in 33.9%, and renal replacement therapy in 28.1%.
      ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality
      were shock (OR, 3.77; 95% CI, 1.93-7.36), SOFA score at day 1 (OR, 1.19; 95% CI,
      1.10-1.30), and direct admission (OR, 0.52; 95% CI, 0.28-0.97). Neither
      comorbidities nor SRD characteristics were associated with survival. CONCLUSIONS:
      In patients with SRDs, critical care management is mostly needed only in patients
      with a previously known SRD; however, diagnosis can be made in the ICU for 12% of
      patients. Infection and SRD exacerbation account for more than two-thirds of
      these situations, both targeting chiefly the lungs. Direct admission to the ICU
      may improve outcomes.

PMID- 25996560
TI  - Two-Dimensional Porous Micro/Nano Metal Oxides Templated by Graphene Oxide.
AB  - Novel two-dimensional (2D) porous metal oxides with micro-/nanoarchitecture have
      been successfully fabricated using graphene oxide (GO) as a typical sacrificial
      template. GO as a 2D template ensures that the growth and fusion of metal oxides
      nanoparticles is restricted in the 2D plane. A series of metal oxides (NiO,
      Fe2O3, Co3O4, Mn2O3, and NiFe2O4) with similar nanostructure were investigated
      using this simple method. Some of these special nanostructured materials, such as
      NiO, when being used as anode for lithium-ion batteries, can exhibit high
      specific capacity, good rate performance, and cycling stability. Importantly,
      this strategy of creating a 2D porous micro/nano architecture can be easily
      extended to controllably synthesize other binary/polynary metal oxides
      nanostructures for lithium-ion batteries or other applications. 

PMID- 25996559
TI  - Capturing Spontaneous Membrane Insertion of the Influenza Virus Hemagglutinin
      Fusion Peptide.
AB  - Hemagglutinin (HA) is a protein located on the surface of the influenza virus
      that mediates viral fusion to the host cellular membrane. During the fusion
      process the HA fusion peptide (HAfp), formed by the first 23 N-terminal residues
      of HA and structurally characterized by two alpha helices (Helix A and Helix B)
      tightly packed in a hairpin-like arrangement, is the only part of the virus in
      direct contact with the host membrane. After encountering the host cell, HAfp is
      believed to insert into the membrane, thereby initiating the fusion of the viral
      and host membranes. Detailed characterization of the interactions between the
      HAfp and cellular membrane is therefore of high relevance to the mechanism of
      viral entry into the host cell. Employing HMMM membrane representation with
      enhanced lipid mobility, we have performed a large set of independent simulations
      of unbiased membrane binding of HAfp. We have been able to capture spontaneous
      binding and insertion of HAfp consistently in nearly all the simulations. A
      reproducible membrane-bound configuration emerges from these simulations, despite
      employing a diverse set of initial configurations. Extension of several of the
      simulations into full membrane systems confirms the stability of the membrane
      bound form obtained from HMMM binding simulations. The resulting model allows for
      the characterization of important interactions between the peptide and the
      membrane and the details of the binding process of the peptide for the first
      time. Upon membrane binding, Helix A inserts much deeper into the membrane than
      Helix B, suggesting that the former is responsible for hydrophobic anchoring of
      the peptide into the membrane. Helix B, in contrast, is found to establish major
      amphipathic interactions at the interfacial region thereby contributing to
      binding strength of HAfp. 

PMID- 25996561
TI  - Cloud Point Extraction for Electroanalysis: Anodic Stripping Voltammetry of
      Cadmium.
AB  - Cloud point extraction (CPE) is a well-established technique for the
      preconcentration of hydrophobic species from water without the use of organic
      solvents. Subsequent analysis is then typically performed via atomic absorption
      spectroscopy (AAS), UV-vis spectroscopy, or high performance liquid
      chromatography (HPLC). However, the suitability of CPE for electroanalytical
      methods such as stripping voltammetry has not been reported. We demonstrate the
      use of CPE for electroanalysis using the determination of cadmium (Cd(2+)) by
      anodic stripping voltammetry (ASV). Rather than using the chelating agents which
      are commonly used in CPE to form a hydrophobic, extractable metal complex, we
      used iodide and sulfuric acid to neutralize the charge on Cd(2+) to form an
      extractable ion pair. This offers good selectivity for Cd(2+) as no interferences
      were observed from other heavy metal ions. Triton X-114 was chosen as the
      surfactant for the extraction because its cloud point temperature is near room
      temperature (22-25  degrees C). Bare glassy carbon (GC), bismuth-coated glassy
      carbon (Bi-GC), and mercury-coated glassy carbon (Hg-GC) electrodes were compared
      for the CPE-ASV. A detection limit for Cd(2+) of 1.7 nM (0.2 ppb) was obtained
      with the Hg-GC electrode. ASV with CPE gave a 20x decrease (4.0 ppb) in the
      detection limit compared to ASV without CPE. The suitability of this procedure
      for the analysis of tap and river water samples was demonstrated. This simple,
      versatile, environmentally friendly, and cost-effective extraction method is
      potentially applicable to a wide variety of transition metals and organic
      compounds that are amenable to detection by electroanalytical methods. 

PMID- 25996562
TI  - Structures and Energetics of Protonated Clusters of Methylamine with
      Phenylalanine Analogs, Characterized by Infrared Multiple Photon Dissociation
      Spectroscopy and Electronic Structure Calculations.
AB  - Gas-phase clusters of protonated methylamine and phenylalanine (Phe) derivatives
      have been studied using infrared multiple photon dissociation (IRMPD)
      spectroscopy in combination with electronic structure calculations at the MP2/aug
      cc-pVTZ//B3LYP/6-311+G(d,p) level of theory. Experiments were performed on
      several Phe derivatives including 4-chloro-l-phenylalanine (4Chloro-Phe), 4-nitro
      l-phenylalanine (4Nitro-Phe), 3-cyano-l-phenylalanine (3Cyano-Phe), and 3
      trifluoromethyl-l-phenylalanine (3CF3-Phe). Through comparisons between
      experimental IRMPD spectra and stimulated spectra obtained by electronic
      structure calculations, charge-solvated structures were found to be prevalent in
      both 4Chloro-Phe and 4Nitro-Phe, whereas 3Cyano-Phe favored zwitterionic
      structures and 3-CF3-Phe likely have both zwitterionic and charge-solvated
      structures present. 

PMID- 25996563
TI  - Effect of different aerodynamic time trial cycling positions on muscle activation
      and crank torque.
AB  - To reduce air resistance, time trial cyclists and triathletes lower their torso
      angle. The aim of this study was to investigate the effect of lowering time trial
      torso angle positions on muscle activation patterns and crank torque
      coordination. It was hypothesized that small torso angles yield a forward shift
      of the muscle activation timing and crank torque. Twenty-one trained cyclists
      performed three exercise bouts at 70% maximal aerobic power in a time trial
      position at three different torso angles (0 degrees , 8 degrees , and 16 degrees
      ) at a fixed cadence of 85 rpm. Measurements included surface electromyography,
      crank torques and gas exchange. A significant increase in crank torque range and
      forward shift in peak torque timing was found at smaller torso angles. This
      relates closely with the later onset and duration of the muscle activation found
      in the gluteus maximus muscle. Torso angle effects were only observed in proximal
      monoarticular muscles. Moreover, all measured physiological variables (oxygen
      consumption, breathing frequency, minute ventilation) were significantly
      increased with lowering torso angle and hence decreased the gross efficiency. The
      findings provide support for the notion that at a cycling intensity of 70%
      maximal aerobic power, the aerodynamic gains outweigh the
      physiological/biomechanical disadvantages in trained cyclists. 

PMID- 25996565
TI  - Selenium, selenoproteins and neurodegenerative diseases.
AB  - It is unsurprising that our understanding of the role of selenium in neurological
      function is somewhat immature, considering its relatively recent discovery as an
      essential element to human health. Selenocysteine, the 21st amino acid, is the
      defining feature of the 25 selenoprotein-encoding genes so far discovered within
      the human genome. The low abundance of these proteins in the brain belies the
      integral role they play in normal neurological function, from well-characterised
      antioxidant activity in the periphery to poorly understood mechanisms that
      modulate mitochondrial function and response to brain pathology. Selenium has
      been identified as playing a role in several neurodegenerative disorders,
      including Alzheimer's and Parkinson's disease, though its function as a 'cause or
      effect' of disease process remains unclear. This review discusses selenium
      metabolism in detail, specifically with regard to the role it plays within the
      central nervous system, and examines the most current literature investigating
      how selenium may be involved in chronic diseases of the central nervous system. 

PMID- 25996566
TI  - Utility of Gallium-68 DOTANOC PET/CT in the localization of Tumour-induced
      osteomalacia.
AB  - BACKGROUND: Tumour-induced osteomalacia (TIO) is a rare disorder characterized by
      hypophosphataemic osteomalacia caused by small mesenchymal tumours secreting
      fibroblast growth factor 23 (FGF 23). The most difficult part in the management
      of these patients is the localization of tumours causing TIO. OBJECTIVE: We
      describe the utility of Gallium (Ga)-68 DOTANOC PET/CT in the localization of
      tumours causing TIO. PATIENTS AND METHODS: The study was conducted in a single
      tertiary referral university teaching hospital in India. Ten patients with TIO
      who underwent Ga-68 DOTANOC PET/CT from the time period 2009 to 2014 were
      included in this study. Their detailed clinical history, biochemical parameters,
      imaging modalities, surgical interventions, histopathology and outcomes were
      reviewed. RESULTS: Ga-68 DOTANOC PET/CT could correctly localize the tumours in
      TIO in 9 of the 10 cases in which it was performed. Complete resection of the
      tumour led to full clinical recovery in six of the ten patients; two patients who
      had partial resection and one patient who underwent radiofrequency ablation
      showed partial remission. One patient in whom Ga-68 DOTANOC PET/CT was positive
      in vertebral body with a low standardized uptake value (SUV) did not show up the
      tumour on surgery. CONCLUSIONS: We conclude that Ga-68 DOTANOC PET/CT can be used
      as the first imaging modality in patients diagnosed with TIO. The extremely good
      outcome following the resection of these small otherwise undiagnosed tumours far
      outweighs its cost even in resource limited settings.

PMID- 25996568
TI  - Review of the Global Distribution of Foot-and-Mouth Disease Virus from 2007 to
      2014.
AB  - Foot-and-mouth disease (FMD) virus affects livestock worldwide. There are seven
      different serotypes, each with a diversity of topotypes, genetic lineages and
      strains. Some lineages have different properties that may contribute to sporadic
      spread beyond their recognized endemic areas. The objective of this study was to
      review the most significant FMD epidemiological events that took place worldwide
      between 2007 and 2014. Severe epidemics were caused by FMD virus (FMDV) lineage
      O/Asia/Mya-98 in Japan and South Korea in 2010, both previously free of disease.
      In India, where FMD is endemic, the most important event was the re-emergence of
      lineage O/ME-SA/Ind-2001 in 2008. Notably, this lineage, normally restricted to
      India, Bangladesh, Nepal and Bhutan, was also found in Saudi Arabia and Libya in
      2013 and has caused several outbreaks in Tunisia and Algeria in 2014-2015. In
      January 2011, FMDV-positive wild boars were found in Bulgaria, where the disease
      last occurred in 1996, followed by 12 outbreaks in livestock infected with FMDV
      O/ME-SA/PanAsia2. In 2012, FMDV SAT2 caused outbreaks in Egypt and the
      Palestinian Autonomous Territories. Another significant event was the emergence
      of FMDV Asia1 Sindh-08 in the Middle East. In South America, one outbreak of FMDV
      serotype O, topotype Euro-SA was reported in Paraguay in 2011, which was
      recognized as FMD-free with vaccination at the time. Lessons learned from past
      events, point out the need for an integrated strategy that comprises coordinated
      global and regional efforts for FMDV control and surveillance. Specific local
      characteristics related to host, environment and virus that condition FMD
      occurrence should be carefully considered and incorporated to adapt appropriate
      strategies into local plans. In this review, we compiled relevant epidemiological
      FMD events to provide a global overview of the current situation. We further
      discussed current challenges present in different FMD areas.

PMID- 25996567
TI  - Effect of treatment willingness on specialist assessment and treatment uptake for
      hepatitis C virus infection among people who use drugs: the ETHOS study.
AB  - Among people who inject drugs (PWID) with chronic HCV, the association between
      HCV treatment willingness and intent, and HCV specialist assessment and treatment
      were evaluated. The Enhancing Treatment for Hepatitis C in Opioid Substitution
      Settings (ETHOS) is a prospective observational cohort. Recruitment was through
      six opioid substitution treatment clinics, two community health centres and one
      Aboriginal community controlled health organisation in Australia. Analyses were
      performed using logistic regression. Among 415 participants (mean age 41 years,
      71% male), 67% were 'definitely willing' to receive HCV treatment and 70%
      reported plans to initiate therapy 12 months postenrolment. Those definitely
      willing to receive HCV treatment were more likely to undergo specialist
      assessment (64% vs 32%, P < 0.001) and initiate therapy (36% vs 9%, P < 0.001),
      compared to those with lower treatment willingness. Those with early HCV
      treatment plans were more likely to undergo specialist assessment (65% vs 27%, P
      < 0.001) and initiate therapy (36% vs 5%, P < 0.001), compared to those without
      early plans. In adjusted analyses, HCV treatment willingness independently
      predicted specialist assessment (aOR 3.06, 95% CI 1.90, 4.94) and treatment
      uptake (aOR 4.33, 95% CI 2.14, 8.76). In adjusted analysis, having early HCV
      treatment plans independently predicted specialist assessment (aOR 4.38, 95% CI
      2.63, 7.29) and treatment uptake (aOR 9.79, 95% CI 3.70, 25.93). HCV treatment
      willingness was high and predicted specialist assessment and treatment.
      Strategies for enhanced HCV care should be developed with an initial focus on
      people willing to receive treatment and to increase treatment willingness among
      those less willing.

PMID- 25996569
TI  - Postpartum sexual health: a principle-based concept analysis.
AB  - AIM: The aim of this study is to report an analysis of the concept of postpartum
      sexual health. BACKGROUND: Postpartum sexual health is a minimally understood
      concept, most often framed within physical/biological dimensions or as a
      'checklist' task in postpartum information provision. This has the potential to
      leave women unprepared to manage transient or normative sexual health changes
      after childbirth. For meaningful discussions, clarity and understanding of
      postpartum sexual health is required. DESIGN: A principle-based method of concept
      analysis. DATA SOURCES: The databases of PubMed, CINAHL, Maternity and Infant
      Care, PsychInfo, Web of Science, EMBASE, SCOPUS and Social Science Index were
      systematically searched, from their earliest dates, using a combination of key
      terms, including; 'sexual health', 'sexual function', 'dyspareunia', 'sexuality',
      'sexual desire', 'sexual dysfunction', 'postnatal' and 'postpartum', resulting in
      a final included dataset of 91 studies. METHODS: Using the principle-based
      approach, postpartum sexual health was analysed under the four philosophical
      principles of epistemological, pragmatic, linguistic and logical. RESULTS:
      Philosophically, postpartum sexual health is underdeveloped as a concept. A
      precise theoretical definition remains elusive and, presently, postpartum sexual
      health cannot be separated theoretically from sexuality and sexual function.
      Identified antecedents include an instrument free birth, an intact perineum and
      avoidance of episiotomy. Attributes include sexual arousal, desire, orgasm,
      sexual satisfaction and resumption of sexual intercourse. Outcomes are sexual
      satisfaction and a satisfying intimate relationship with one's partner.
      CONCLUSION: Postpartum sexual health is conceptually immature with limited
      applicability in current midwifery practice.

PMID- 25996570
TI  - Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three
      High-Risk Patients.
AB  - Corneas with severe pathologies have a high risk of rejection when conventionally
      grafted with human donor tissues. In this early observational study, we grafted
      bioengineered corneal implants made from recombinant human collagen and synthetic
      phosphorylcholine polymer into three patients for whom donor cornea
      transplantation carried a high risk of transplant failure. These patients
      suffered from corneal ulcers and recurrent erosions preoperatively. The implants
      provided relief from pain and discomfort, restored corneal integrity by promoting
      endogenous regeneration of corneal tissues, and improved vision in two of three
      patients. Such implants could in the future be alternatives to donor corneas for
      high-risk patients, and therefore, merits further testing in a clinical trial. 

PMID- 25996571
TI  - Spatiotemporal trends of illegal activities from ranger-collected data in a
      Ugandan national park.
AB  - Within protected areas, biodiversity loss is often a consequence of illegal
      resource use. Understanding the patterns and extent of illegal activities is
      therefore essential for effective law enforcement and prevention of biodiversity
      declines. We used extensive data, commonly collected by ranger patrols in many
      protected areas, and Bayesian hierarchical models to identify drivers, trends,
      and distribution of multiple illegal activities within the Queen Elizabeth
      Conservation Area (QECA), Uganda. Encroachment (e.g., by pastoralists with
      cattle) and poaching of noncommercial animals (e.g., snaring bushmeat) were the
      most prevalent illegal activities within the QECA. Illegal activities occurred in
      different areas of the QECA. Poaching of noncommercial animals was most widely
      distributed within the national park. Overall, ecological covariates, although
      significant, were not useful predictors for occurrence of illegal activities.
      Instead, the location of illegal activities in previous years was more important.
      There were significant increases in encroachment and noncommercial plant
      harvesting (nontimber products) during the study period (1999-2012). We also
      found significant spatiotemporal variation in the occurrence of all activities.
      Our results show the need to explicitly model ranger patrol effort to reduce
      biases from existing uncorrected or capture per unit effort analyses.
      Prioritization of ranger patrol strategies is needed to target illegal
      activities; these strategies are determined by protected area managers, and
      therefore changes at a site-level can be implemented quickly. These strategies
      should also be informed by the location of past occurrences of illegal activity:
      the most useful predictor of future events. However, because spatial and temporal
      changes in illegal activities occurred, regular patrols throughout the protected
      area, even in areas of low occurrence, are also required. 

PMID- 25996573
TI  - Nitric Oxide Regulation of Bacterial Biofilms.
AB  - Biofilms are surface-associated, multicellular communities of bacteria. Once
      established, they are extremely difficult to eradicate by antimicrobial
      treatment. It has been demonstrated in many species that biofilm formation may be
      regulated by the diatomic signaling molecule nitric oxide (NO). Although this is
      still a relatively new area of research, we review here the literature reporting
      an effect of NO on bacterial biofilm formation, emphasizing dose-dependent
      responses to NO concentrations when possible. Where it has been investigated, the
      underlying NO sensors or signaling pathways are also discussed. Most of the
      examples of NO-mediated biofilm regulation have been documented with exogenously
      applied NO, but we also survey possible natural sources of NO in biofilm
      regulation, including endogenously generated NO. Finally, because of the apparent
      broad-spectrum, antibiofilm effects of NO, NO-releasing materials and prodrugs
      have also been explored in this minireview. 

PMID- 25996572
TI  - 3D dento-maxillary osteolytic lesion and active contour segmentation pilot study
      in CBCT: semi-automatic vs manual methods.
AB  - OBJECTIVES: This study was designed to evaluate the reliability of a semi
      automatic segmentation tool for dento-maxillary osteolytic image analysis
      compared with manually defined segmentation in CBCT scans. METHODS: Five CBCT
      scans were selected from patients for whom periapical radiolucency images were
      available. All images were obtained using a ProMax(r) 3D Mid Planmeca (Planmeca
      Oy, Helsinki, Finland) and were acquired with 200-MUm voxel size. Two clinicians
      performed the manual segmentations. Four operators applied three different semi
      automatic procedures. The volumes of the lesions were measured. An analysis of
      dispersion was made for each procedure and each case. An ANOVA was used to
      evaluate the operator effect. Non-paired t-tests were used to compare semi
      automatic procedures with the manual procedure. Statistical significance was set
      at alpha = 0.01. RESULTS: The coefficients of variation for the manual procedure
      were 2.5-3.5% on average. There was no statistical difference between the two
      operators. The results of manual procedures can be used as a reference. For the
      semi-automatic procedures, the dispersion around the mean can be elevated
      depending on the operator and case. ANOVA revealed significant differences
      between the operators for the three techniques according to cases. CONCLUSIONS:
      Region-based segmentation was only comparable with the manual procedure for
      delineating a circumscribed osteolytic dento-maxillary lesion. The semi-automatic
      segmentations tested are interesting but are limited to complex surface
      structures. A methodology that combines the strengths of both methods could be of
      interest and should be tested. The improvement in the image analysis that is
      possible through the segmentation procedure and CBCT image quality could be of
      value.

PMID- 25996574
TI  - MRI Pre- and Post-Embolization Enhancement Patterns Predict Surgical Outcomes in
      Intracranial Meningiomas.
AB  - PURPOSE: To evaluate the effects of preoperative embolization on overall surgical
      outcomes after meningioma resection and determine whether pre- and
      postembolization tumor enhancement patterns on magnetic resonance imaging (MRI)
      scans can be used to assess the efficacy of embolization. METHODS: We developed a
      prospective database of all patients who underwent surgical resection with or
      without preoperative embolization for extra-axial intracranial meningiomas from
      2004 to 2010. Using specialized computer software, the total volume of
      enhancement was calculated in pre- and postembolization MRI scans to quantify the
      percentage of embolization, which was described as the embolization fraction
      (EF). RESULTS: A total of 89 patients underwent surgical resection. Fifty two
      patients underwent embolization prior to surgery. Tumor location significantly
      correlated with the decision to embolize preoperatively. Adequate embolization
      was achieved in 58% of patients. Forty four patients (84.6%) had a postsurgical
      Karnofsky performance score (KPS) of 80 or above, while 46 patients (88.4%) had a
      postsurgical Glascow Outcome Score (GOS) of 4 or 5. The mean EF was 25.03% with a
      median of 18.72%. A greater extent of embolization as quantified by EF led to
      decreased intraoperative blood loss (r = -.319, P = .022) and better postsurgical
      outcomes as defined by KPS (r = .279, P = .044). CONCLUSIONS: Pre- and
      postembolization tumor enhancement patterns on magnetic resonance imaging defined
      as EF correlate with improved surgical facilitation and postoperative functional
      outcomes in the management of intracranial meningioma.

PMID- 25996575
TI  - LC3 is a novel substrate for the mammalian Hippo kinases, STK3/STK4.
AB  - The Atg8 family protein LC3 is indispensible for autophagy and plays critical
      roles in multiple steps of the process. Despite this functional significance, the
      regulation of LC3 activity at the posttranslational level remains poorly
      understood. In a recent study, we report that the conserved Ste20 kinases STK3
      and STK4, the mammalian orthologs of Hippo kinase, are essential for autophagy in
      diverse organisms, and both can phosphorylate LC3 on amino acid Thr50. STK3/STK4
      mediated phosphorylation is critical for fusion of autophagosomes with lysosomes,
      as well as the ability of cells to clear intracellular bacteria, an established
      cargo for autophagy. Our discovery of a novel mode of autophagy regulation
      involving direct phosphorylation of LC3 by STK3/STK4 significantly enhances our
      molecular understanding of the autophagy process. Moreover, our findings raise
      the exciting possibility that STK3/STK4's known roles in immunity are exerted
      through their ability to regulate autophagy via LC3 phosphorylation. 

PMID- 25996576
TI  - Comparison of Axxent-Xoft, (192)Ir and (60)Co high-dose-rate brachytherapy
      sources for image-guided brachytherapy treatment planning for cervical cancer.
AB  - OBJECTIVE: To evaluate the dosimetric differences and similarities between
      treatment plans generated with Axxent-Xoft electronic brachytherapy source (Xoft
      EBS), (192)Ir and (60)Co for tandem and ovoids (T&O) applicators. METHODS: In
      this retrospective study, we replanned 10 patients previously treated with
      (192)Ir high-dose-rate brachytherapy. Prescription was 7 Gy * 4 fractions to
      Point A. For each original plan, we created two additional plans with Xoft-EBS
      and (60)Co. The dose to each organ at risk (OAR) was evaluated in terms of V(35%)
      and V(50%), the percentage volume receiving 35% and 50% of the prescription dose,
      respectively, and D(2cc), highest dose to a 2 cm(3) volume of an OAR. RESULTS:
      There was no difference between plans generated by (192)Ir and (60)Co, but the
      plans generated using Xoft-EBS showed a reduction of up to 50% in V(35%), V(50%)
      and D(2cc). The volumes of the 200% and 150% isodose lines, however, were 74% and
      34% greater than the comparable volumes generated with the (192)Ir source. Point
      B dose was on average only 16% of the Point A dose for plans generated with Xoft
      EBS compared with 30% for plans generated with (192)Ir or (60)Co. CONCLUSION: The
      Xoft-EBS can potentially replace either (192)Ir or (60)Co in T&O treatments. Xoft
      EBS offers either better sparing of the OARs compared with (192)Ir or (60)Co or
      at least similar sparing. Xoft-EBS-generated plans had higher doses within the
      target volume than (192)Ir- or (60)Co-generated ones. ADVANCES IN KNOWLEDGE: This
      work presents newer knowledge in dosimetric comparison between Xoft-EBS, (192)Ir
      or (60)Co sources for T&O implants.

PMID- 25996577
TI  - Dosimetric evaluation of compensator intensity modulation-based stereotactic body
      radiotherapy for Stage I non-small-cell lung cancer.
AB  - OBJECTIVE: To evaluate the dosimetry of compensator intensity modulation-based
      stereotactic body radiotherapy (SBRT) [non-coplanar intensity-modulated
      radiotherapy (ncIMRT)], its use was compared with that of three-dimensional
      conformation-based SBRT, for patients with Stage I non-small-cell lung cancer
      (NSCLC). METHODS: 21 consecutive patients with Stage I NSCLC were treated with
      ncIMRT or SBRT at Tokyo Medical University. To compare the two techniques, ncIMRT
      and SBRT plans for each patient were generated, where the planning target volume
      (PTV) coverages were adjusted to be equivalent to each other. The prescribed dose
      was set as 75 Gy in 30 fractions. PTV coverage, conformity index, conformation
      number (CN) and homogeneity index (HI) were used to compare the two strategies.
      RESULTS: There was no statistically significant difference between PTV coverage
      for the 100%, 95% and 90% dose levels in the SBRT plan and those in the ncIMRT
      plan. The CN values were 0.53 +/- 0.13 in the SBRT plan and 0.72 +/- 0.10 in the
      ncIMRT plan. These values were significantly better than those of the SBRT plan
      (p < 0.001). The HI in the ncIMRT plan was 1.04 +/- 0.03%, which was also
      significantly better than that of SBRT. CONCLUSION: The ncIMRT plan provided
      superior conformity and reduced the doses to the lung for patients with Stage I
      NSCLC. ADVANCES IN KNOWLEDGE: The delivery technique with compensator intensity
      modulation-based SBRT was evaluated. Concerning target motion, this is thought to
      be more robust and safer than SBRT for early-stage NSCLC.

PMID- 25996578
TI  - Pilot study on interfractional and intrafractional movements using surface
      infrared markers and EPID for patients with rectal cancer treated in the prone
      position.
AB  - OBJECTIVE: To evaluate interfractional and intrafractional movement of patients
      with rectal cancer during radiotherapy with electronic portal imaging device
      (EPID) and surface infrared (IR) markers. METHODS: 20 patients undergoing
      radiotherapy for rectal cancer with body mass index ranging from 18.5 to 30 were
      enrolled. Patients were placed in the prone position on a couch with a leg
      pillow. Three IR markers were put on the surface of each patient and traced by
      two stereo cameras during radiotherapy on a twice-weekly basis. Interfractional
      isocentre movement was obtained with EPID images on a weekly basis. Movement of
      the IR markers was analysed in correlation with the isocentre movement obtained
      from the EPID images. RESULTS: The maximum right-to-left (R-L) movement of the
      laterally located markers in the horizontal isocentre plane was correlated with
      isocentre translocation with statistical significance (p = 0.018 and 0.015,
      respectively). Movement of the surface markers was cyclical. For centrally
      located markers, the 95% confidence intervals for the average amplitude in the R
      L, cranial-to-caudal (C-C) and anterior-to-posterior (A-P) directions were 0.86,
      2.25 and 3.48 mm, respectively. In 10 patients, intrafractional movement
      exceeding 5 mm in at least one direction was observed. Time-dependent systematic
      movement of surface markers during treatment, which consisted of continuous
      movement towards the cranial direction and a sail back motion in the A-P
      direction, was also observed. CONCLUSION: Intrafractional movement of surface
      markers has both cyclic components and time-dependent systematic components.
      Marker deviations exceeding 5 mm were mainly seen in the A-P direction. Pre- or
      post-treatment EPID images may not provide adequate information regarding
      intrafractional movement because of systematic movement in the A-P direction
      during radiotherapy. ADVANCES IN KNOWLEDGE: This work uncovered a sail back
      motion of patients in the A-P direction during radiotherapy. Pre- or post
      treatment EPID images may not provide accurate positioning of patients in the A-P
      direction because of this time-dependent intrafractional motion.

PMID- 25996579
TI  - Age-dependent decrease of anti-HBs titers and effect of booster doses using 2
      different vaccines in Palestinian children vaccinated in early childhood.
AB  - Immunization against hepatitis B virus (HBV) has proven to be highly effective
      and led to significant reduction of new infections worldwide. However, protective
      immunity measured by anti-HBs titers may decrease to critical levels in the years
      after basal immunization, particularly in case of exposure to HBV variants
      different from the vaccine strain. We tested 400 Palestinian children between one
      and 19 years of age for their anti-HBs titer, challenged the immune memory of
      those with low or absent anti-HBs with 2 types of hepatitis B vaccines and
      determined thereafter the anti-HBs titer. At the age of one, 92.2% of the
      children presented with protective anti-HBs titers (>= 10 mIU/ml) with the
      majority having >= 100 mIU/ml. Protective immunity was still high at ages 2
      (87.5%) and 4 (95%), declining by age 5 and 6 (from 69.2% to 66.7%) and down to
      an average of 39.8% between the ages of 7 and 19. 160 children with a
      nonprotective or low immune response challenged with either the yeast-derived
      Engerix-B or the mammalian cell-derived preS1-containing Sci-B-Vac vaccine showed
      an anamnestic immune response. 92.4% and 85.9% of the children challenged with
      one dose Sci-B-Vac and Engerix-B presented with anti-HBs titers >100 mIU/ml
      respectively. Our results reveal that vaccine-induced protective anti-HBs titers
      against HBV decrease rapidly beyond the age of 6 in Palestinian children, but can
      be strongly enhanced with a single booster vaccine dose, independent of brand and
      antigen composition. Our data suggest that a booster vaccine dose against HBV
      during school years may be useful.

PMID- 25996580
TI  - Physiologically Modeled Pulse Dynamics to Improve Function in In Vitro
      Endothelialized Small-Diameter Vascular Grafts.
AB  - The lack of a functional endothelium on small-diameter vascular grafts leads to
      intimal hyperplasia and thrombotic occlusion. Shear stress conditioning through
      controlled hydrodynamics within in vitro perfusion bioreactors has shown promise
      as a mechanism to drive endothelial cell (EC) phenotype from an activated, pro
      inflammatory wound state toward a quiescent functional state that inhibits
      responses that lead to occlusive failure. As part of an overall design strategy
      to engineer functional vascular grafts, we present a novel two-phase shear
      conditioning approach to improve graft endothelialization. Axial rotation was
      first used to seed uniform EC monolayers onto the lumenal surface of
      decellularized scaffolds derived from the human umbilical vein. Using computer
      controlled perfusion circuits, a flow-ramping paradigm was applied to adapt
      endothelia to arterial levels of fluid shear stress and pressure without graft
      denudation. The effects of constant pulse frequencies (CF) on EC quiescence were
      then compared with pulse frequencies modeled from temporal fluctuations in blood
      flow observed in vivo, termed physiologically modeled pulse dynamics (PMPD).
      Constructs exposed to PMPD for 72 h expressed a more functional transcriptional
      profile, lower metabolic activity (39.8% +/- 8.4% vs. 62.5% +/- 11.5% reduction,
      p = 0.012), and higher nitric oxide production (80.42 +/- 23.93 vs. 48.75 +/-
      6.93 nmol/10(5) cells, p = 0.028) than those exposed to CF. By manipulating in
      vitro flow conditions to mimic natural physiology, endothelialized vascular
      grafts can be stimulated to express a nonactivated phenotype that would better
      inhibit peripheral cell adhesion and smooth muscle cell hyperplasia, conditions
      that typically lead to occlusive failure. Development of robust, functional
      endothelia on vascular grafts by modulation of environmental conditions within
      perfusion bioreactors may ultimately improve clinical outcomes in vascular bypass
      grafting.

PMID- 25996581
TI  - Psychological Counseling of Female Fertility Preservation Patients.
AB  - Young cancer patients are increasingly interested in preserving their fertility
      prior to undergoing gonadotoxic therapies. Although the medical safety and
      treatment protocols for fertility preservation have been well documented, limited
      research has addressed the emotional issues that arise in fertility preservation
      patients. We briefly review the literature on the psychosocial issues in adult
      female fertility preservation treatment and describe our experiences within this
      patient population. Our findings suggest that several important issues to be
      addressed during the psychological counseling of adult female fertility
      preservation patients include: (1) preexisting psychological distress in patients
      undergoing treatment, (2) choice of fertility preservation strategy in the face
      of an uncertain relationship future, (3) decision making regarding use of third
      party reproduction (e.g., sperm/egg donation, gestational surrogacy), (4)
      treatment expectations regarding pregnancy and miscarriage, (5) ethical issues
      related to treatment including the creation, cryopreservation, and disposition of
      embryos/oocytes, and (6) decision regret from patients who declined fertility
      preservation. 

PMID- 25996582
TI  - Low Recent Protein Intake Predicts Cancer-Related Fatigue and Increased Mortality
      in Patients with Advanced Tumor Disease Undergoing Chemotherapy.
AB  - Cancer patients, in general, suffer from anorexia hence diminished nutritional
      intake. In a prospective observational study, we investigated the impact of
      recent energy and protein intake on cancer-related fatigue and 6-month mortality
      in patients undergoing chemotherapy. Recent protein and energy intake was
      assessed by 24-h recall in 285 patients. Cancer-related fatigue was determined by
      Brief Fatigue Inventory, and fat free mass index (FFMI) was assessed with
      bioelectrical impedance analysis. Symptoms with the validated German version of
      European Organization for Research and Treatment of Cancer Quality of Life Core
      Questionnaire (30 questions) and 6-month mortality was documented. Risk factors
      of cancer-related fatigue and predictors of mortality were investigated with
      logistic regression analysis and stepwise Cox regression analysis, respectively.
      Low protein intake (<1 g/kg body weight) was found in 66% of patients, who were
      characterized by higher age, weight, and body mass index. Recent protein intake
      emerged as the strongest contributor to cancer-related fatigue followed by
      nausea/vomiting, insomnia, and age. Reduced protein intake, male sex, number of
      comorbidities, and FFMI were identified as significant predictors for increased 6
      month mortality. In conclusion, a low recent protein intake assessed by 24-h
      recall is associated with a more than twofold higher risk of cancer-related
      fatigue and 6-month mortality. Every effort should be taken to assess and
      guarantee proper nutritional intake in patients undergoing chemotherapy.

PMID- 25996585
TI  - MIEN1 promotes oral cancer progression and implicates poor overall survival.
AB  - Oral squamous cell carcinoma is a highly malignant tumor with the potential to
      invade local and distant sites and promote lymph node metastasis. Major players
      underlying the molecular mechanisms behind tumor progression are yet to be fully
      explored. Migration and invasion enhancer 1 (MIEN1), a novel protein
      overexpressed in various cancers, facilitates cell migration and invasion. In the
      present study we investigated the expression and role of MIEN1 in oral cancer
      progression using an in vitro model, patient derived oral tissues and existing
      TCGA data. Expression analysis using immortalized normal and cancer cells
      demonstrated increased expression of MIEN1 in cancer. Assays performed after
      MIEN1 knockdown in OSC-2 cells showed decreased migration, invasion and filopodia
      formation; while MIEN1 overexpression in DOK cells increased these
      characteristics and also up-regulated some Akt/NF-kappaB effectors, thereby
      suggesting an important role for MIEN1 in oral cancer progression.
      Immunohistochemical staining and analyses of oral tissue specimens, collected
      from patients over multiple visits, revealed significantly more staining in
      severe dysplasia and squamous cell carcinoma compared to mildly dysplastic or
      hyperplastic tissues. Finally, this was corroborated with the TCGA dataset, where
      MIEN1 expression was not only higher in intermediate and high grade cancer with
      significantly lower survival but also correlated with smoking. In summary, we
      demonstrate that MIEN1 expression not only positively correlates with oral cancer
      progression but also seems to be a critical molecular determinant in migration
      and invasion of oral cancer cells, thereby, playing a possible role in their
      metastatic dissemination. 

PMID- 25996586
TI  - Tapping Into Valuable Expertise From Private Practitioners and Academicians:
      Casting a Wider Net.

PMID- 25996589
TI  - Alterations in the Elasticity, Pliability, and Viscoelastic Properties of Facial
      Skin After Injection of Onabotulinum Toxin A.
AB  - IMPORTANCE: This prospective cohort study provides evidence and information on
      the mechanism of action of onabotulinum toxin A on the reduction of skin
      elasticity and pliability. Understanding the natural course that onabotulinum
      toxin A has on the elasticity of skin may help physicians understand why there
      appears to be a progressive reduction in wrinkle levels with repeated treatments.
      OBJECTIVE: To determine whether onabotulinum toxin A increases skin pliability
      and elasticity with a corresponding decrease in the contribution of the
      viscoelastic component of skin resistance. DESIGN, SETTING, AND PARTICIPANTS:
      From October 1, 2012, through June 31, 2013, this prospective cohort study
      enrolled 48 onabotulinum toxin A-naive women (mean [SD] age, 55.2 [11.3] years)
      with a minimum of mild wrinkle levels at the glabella and lateral orbit (43
      completed the study). Patients were treated at a private cosmetic surgery clinic
      with onabotulinum toxin A and assessed at baseline and 2 weeks, 2 months, 3
      months, and 4 months after injection. INTERVENTIONS: Standardized onabotulinum
      toxin A was administered to patients' glabella, supraorbit, and lateral orbit.
      MAIN OUTCOMES AND MEASURES: Skin pliability, elastic recoil, and the ratio of
      viscoelastic resistance (Uv) to elastic resistance (Ue). RESULTS: For the
      supraorbit, there was a significant effect of time on pliability (F = 20.5),
      elastic recoil (F = 6.92), and Uv/Ue ratio (F = 5.6) (P < .001 for all). For the
      glabella, there was a significant effect of time on pliability (F = 32.23),
      elastic recoil (F = 31.66), and Uv/Ue ratio (F = 10.11) (P < .001 for all). For
      the lateral orbit, there was a significant effect of time on pliability (F =
      15.83, P < .001), elastic recoil (F = 11.43, P < .001), and Uv/Ue ratio (F =
      10.60, P = .009). CONCLUSIONS AND RELEVANCE: This study provides further evidence
      that there is an alteration in biomechanical properties of the skin after
      injection with onabotulinum toxin A. This effect appears to last up to 4 months
      in the glabella and up to 3 months at other sites. The decrease in the Uv/Ue
      ratio suggests onabotulinum toxin A injection does not result in an increase in
      tissue edema suggestive of an inflammatory reaction within the skin. However, it
      remains unclear whether this is due to an intrinsic property of the medication or
      another unrecognized mechanism. LEVEL OF EVIDENCE: 2.

PMID- 25996590
TI  - Placental mitochondrial methylation and exposure to airborne particulate matter
      in the early life environment: An ENVIRONAGE birth cohort study.
AB  - Most research to date has focused on epigenetic modifications in the nuclear
      genome, with little attention devoted to mitochondrial DNA (mtDNA). Placental
      mtDNA content has been shown to respond to environmental exposures that induce
      oxidative stress, including airborne particulate matter (PM). Damaged or non
      functioning mitochondria are specifically degraded through mitophagy, exemplified
      by lower mtDNA content, and could be primed by epigenetic modifications in the
      mtDNA. We studied placental mtDNA methylation in the context of the early life
      exposome. We investigated placental tissue from 381 mother-newborn pairs that
      were enrolled in the ENVIRONAGE birth cohort. We determined mtDNA methylation by
      bisulfite-pyrosequencing in 2 regions, i.e., the D-loop control region and 12S
      rRNA (MT-RNR1), and measured mtDNA content by qPCR. PM2.5 exposure was calculated
      for each participant's home address using a dispersion model. An interquartile
      range (IQR) increment in PM2.5 exposure over the entire pregnancy was positively
      associated with mtDNA methylation (MT-RNR1: +0.91%, P = 0.01 and D-loop: +0.21%,
      P = 0.05) and inversely associated with mtDNA content (relative change of 
      15.60%, P = 0.001) in placental tissue. mtDNA methylation was estimated to
      mediate 54% [P = 0.01 (MT-RNR1)] and 27% [P = 0.06 (D-loop)] of the inverse
      association between PM2.5 exposure and mtDNA content. This study provides new
      insight into the mechanisms of altered mitochondrial function in the early life
      environment. Epigenetic modifications in the mitochondrial genome, especially in
      the MT-RNR1 region, substantially mediate the association between PM2.5 exposure
      during gestation and placental mtDNA content, which could reflect signs of
      mitophagy and mitochondrial death. 

PMID- 25996591
TI  - Estimating impacts of climate change policy on land use: an agent-based modelling
      approach.
AB  - Agriculture is important to New Zealand's economy. Like other primary producers,
      New Zealand strives to increase agricultural output while maintaining
      environmental integrity. Utilising modelling to explore the economic,
      environmental and land use impacts of policy is critical to understand the likely
      effects on the sector. Key deficiencies within existing land use and land cover
      change models are the lack of heterogeneity in farmers and their behaviour, the
      role that social networks play in information transfer, and the abstraction of
      the global and regional economic aspects within local-scale approaches. To
      resolve these issues we developed the Agent-based Rural Land Use New Zealand
      model. The model utilises a partial equilibrium economic model and an agent-based
      decision-making framework to explore how the cumulative effects of individual
      farmer's decisions affect farm conversion and the resulting land use at a
      catchment scale. The model is intended to assist in the development of policy to
      shape agricultural land use intensification in New Zealand. We illustrate the
      model, by modelling the impact of a greenhouse gas price on farm-level land use,
      net revenue, and environmental indicators such as nutrient losses and soil
      erosion for key enterprises in the Hurunui and Waiau catchments of North
      Canterbury in New Zealand. Key results from the model show that farm net revenue
      is estimated to increase over time regardless of the greenhouse gas price. Net
      greenhouse gas emissions are estimated to decline over time, even under a no GHG
      price baseline, due to an expansion of forestry on low productivity land. Higher
      GHG prices provide a greater net reduction of emissions. While social and
      geographic network effects have minimal impact on net revenue and environmental
      outputs for the catchment, they do have an effect on the spatial arrangement of
      land use and in particular the clustering of enterprises. 

PMID- 25996592
TI  - Long-range spin-triplet correlations and edge spin currents in diffusive spin
      orbit coupled SNS hybrids with a single spin-active interface.
AB  - Utilizing a SU(2) gauge symmetry technique in the quasiclassical diffusive
      regime, we theoretically study finite-sized two-dimensional intrinsic spin-orbit
      coupled superconductor/normal-metal/superconductor (S/N/S) hybrid structures with
      a single spin-active interface. We consider intrinsic spin-orbit interactions
      (ISOIs) that are confined within the N wire and absent in the s-wave
      superconducting electrodes (S). Using experimentally feasible parameters, we
      demonstrate that the coupling of the ISOIs and spin moment of the spin-active
      interface results in maximum singlet-triplet conversion and accumulation of spin
      current density at the corners of the N wire nearest the spin-active interface.
      By solely modulating the superconducting phase difference, we show how the
      opposing parities of the charge and spin currents provide an effective venue to
      experimentally examine pure edge spin currents not accompanied by charge
      currents. These effects occur in the absence of externally imposed fields and
      moreover are insensitive to the arbitrary orientations of the interface spin
      moment. The experimental implementation of these robust edge phenomena are also
      discussed. 

PMID- 25996594
TI  - Trends and characteristics of attendance at the emergency department of a Swiss
      university hospital: 2002-2012.
AB  - BACKGROUND: The numbers of people attending emergency departments (EDs) at
      hospitals are increasing. We aimed to analyse trends in ED attendance at a Swiss
      university hospital between 2002 and 2012, focussing on age-related differences
      and hospital admission criteria. METHODS: We used hospital administrative data
      for all patients aged >=16 years who attended the ED (n=298,306) at this
      university hospital between 1 January 2002, and 31 December 2012. We
      descriptively analysed the numbers of ED visits according to the admission year
      and stratified by age (>=65 vs <65 years). RESULTS: People attending the ED were
      on average 46.6 years old (standard deviation 20 years, maximum range 16-99
      years). The annual number of ED attendances grew by n=6,639 (27.6%) from 24,080
      in 2002 to 30,719 in 2012. In the subgroup of patients aged >=65 the relative
      increase was 42.3%, which is significantly higher (Pearson's chi2=350.046, df=10;
      p=0.000) than the relative increase of 23.4% among patients<65 years. The
      subgroup of patients>=65 years attended the ED more often because of diseases
      (n=56,307; 85%) than accidents (n=9,844; 14.9%). This subgroup (patients>=65
      years) was also more often admitted to hospital (Pearson's chi2=23,377.190; df=1;
      p=0.000) than patients<65 years. CONCLUSIONS: ED attendance of patients>=65 years
      increased in absolute and relative terms. The study findings suggest that staff
      of this ED may want to assess the needs of patients>=65 years and, if necessary,
      adjust the services (e.g., adapted triage scales, adapted geriatric screenings,
      and adapted hospital admission criteria).

PMID- 25996593
TI  - Intestinal Colonization Dynamics of Vibrio cholerae.
AB  - To cause the diarrheal disease cholera, Vibrio cholerae must effectively colonize
      the small intestine. In order to do so, the bacterium needs to successfully
      travel through the stomach and withstand the presence of agents such as bile and
      antimicrobial peptides in the intestinal lumen and mucus. The bacterial cells
      penetrate the viscous mucus layer covering the epithelium and attach and
      proliferate on its surface. In this review, we discuss recent developments and
      known aspects of the early stages of V. cholerae intestinal colonization and
      highlight areas that remain to be fully understood. We propose mechanisms and
      postulate a model that covers some of the steps that are required in order for
      the bacterium to efficiently colonize the human host. A deeper understanding of
      the colonization dynamics of V. cholerae and other intestinal pathogens will
      provide us with a variety of novel targets and strategies to avoid the diseases
      caused by these organisms. 

PMID- 25996595
TI  - A revised time tree of the asterids: establishing a temporal framework for
      evolutionary studies of the coffee family (rubiaceae).
AB  - Divergence time analyses in the coffee family (Rubiaceae) have all relied on the
      same Gentianales crown group age estimate, reported by an earlier analysis of the
      asterids, for defining the upper age bound of the root node in their analyses.
      However, not only did the asterid analysis suffer from several analytical
      shortcomings, but the estimate itself has been used in highly inconsistent ways
      in these Rubiaceae analyses. Based on the original data, we here reanalyze the
      divergence times of the asterids using relaxed-clock models and 14 fossil-based
      minimum age constraints. We also expand the data set to include an additional 67
      taxa from Rubiaceae sampled across all three subfamilies recognized in the
      family. Three analyses are conducted: a separate analysis of the asterids, which
      completely mirrors the original asterid analysis in terms of taxon sample and
      data; a separate analysis of the Gentianales, where the result from the first
      analysis is used for defining a secondary root calibration point; and a combined
      analysis where all taxa are analyzed simultaneously. Results are presented in the
      form of a time-calibrated phylogeny, and age estimates for asterid groups,
      Gentianales, and major groups of Rubiaceae are compared and discussed in relation
      to previously published estimates. Our updated age estimates for major groups of
      Rubiaceae provide a significant step forward towards the long term goal of
      establishing a robust temporal framework for the divergence of this biologically
      diverse and fascinating group of plants. 

PMID- 25996596
TI  - Turning Saccharomyces cerevisiae into a Frataxin-Independent Organism.
AB  - Frataxin (Yfh1 in yeast) is a conserved protein and deficiency leads to the
      neurodegenerative disease Friedreich's ataxia. Frataxin is a critical protein for
      Fe-S cluster assembly in mitochondria, interacting with other components of the
      Fe-S cluster machinery, including cysteine desulfurase Nfs1, Isd11 and the Isu1
      scaffold protein. Yeast Isu1 with the methionine to isoleucine substitution
      (M141I), in which the E. coli amino acid is inserted at this position, corrected
      most of the phenotypes that result from lack of Yfh1 in yeast. This suppressor
      Isu1 behaved as a genetic dominant. Furthermore frataxin-bypass activity required
      a completely functional Nfs1 and correlated with the presence of efficient
      scaffold function. A screen of random Isu1 mutations for frataxin-bypass activity
      identified only M141 substitutions, including Ile, Cys, Leu, or Val. In each
      case, mitochondrial Nfs1 persulfide formation was enhanced, and mitochondrial Fe
      S cluster assembly was improved in the absence of frataxin. Direct targeting of
      the entire E. coli IscU to ?yfh1 mitochondria also ameliorated the mutant
      phenotypes. In contrast, expression of IscU with the reverse substitution i.e.
      IscU with Ile to Met change led to worsening of the ?yfh1 phenotypes, including
      severely compromised growth, increased sensitivity to oxygen, deficiency in Fe-S
      clusters and heme, and impaired iron homeostasis. A bioinformatic survey of
      eukaryotic Isu1/prokaryotic IscU database entries sorted on the amino acid
      utilized at the M141 position identified unique groupings, with virtually all of
      the eukaryotic scaffolds using Met, and the preponderance of prokaryotic
      scaffolds using other amino acids. The frataxin-bypassing amino acids Cys, Ile,
      Leu, or Val, were found predominantly in prokaryotes. This amino acid position
      141 is unique in Isu1, and the frataxin-bypass effect likely mimics a conserved
      and ancient feature of the prokaryotic Fe-S cluster assembly machinery. 

PMID- 25996597
TI  - Taspase1 processing alters TFIIA cofactor properties in the regulation of TFIID.
AB  - TFIIA is an important positive regulator of TFIID, the primary promoter
      recognition factor of the basal RNA polymerase II transcription machinery. TFIIA
      antagonises negative TFIID regulators such as negative cofactor 2 (NC2), promotes
      specific binding of the TBP subunit of TFIID to TATA core promoter sequence
      elements and stimulates the interaction of TBP-associated factors (TAFs) in the
      TFIID complex with core promoter elements located downstream of TATA, such as the
      initiator element (INR). Metazoan TFIIA consists of 3 subunits, TFIIAalpha (35
      kDa), beta (19 kDa) and gamma (12 kDa). TFIIAalpha and beta subunits are encoded
      by a single gene and result from site-specific cleavage of a 55 kDa
      TFIIA(alpha/beta) precursor protein by the protease Taspase1. Metazoan cells have
      been shown to contain variable amounts of TFIIA (55/12 kDa) and Taspase1
      processed TFIIA (35/19/12 kDa) depending on cell type, suggesting distinct gene
      specific roles of unprocessed and Taspase1-processed TFIIA. How precisely
      Taspase1 processing affects TFIIA functions is not understood. Here we report
      that Taspase1 processing alters TFIIA interactions with TFIID and the
      conformation of TFIID/TFIIA promoter complexes. We further show that Taspase1
      processing induces increased sensitivity of TFIID/TFIIA complexes to the
      repressor NC2, which is counteracted by the presence of an INR core promoter
      element. Our results provide first evidence that Taspase1 processing affects
      TFIIA regulation of TFIID and suggest that Taspase1 processing of TFIIA is
      required to establish INR-selective core promoter activity in the presence of
      NC2.

PMID- 25996598
TI  - Slow-Onset Inhibition of Mycobacterium tuberculosis InhA: Revealing Molecular
      Determinants of Residence Time by MD Simulations.
AB  - An important kinetic parameter for drug efficacy is the residence time of a
      compound at a drug target, which is related to the dissociation rate constant
      koff. For the essential antimycobacterial target InhA, this parameter is most
      likely governed by the ordering of the flexible substrate binding loop (SBL).
      Whereas the diphenyl ether inhibitors 6PP and triclosan (TCL) do not show loop
      ordering and thus, no slow-binding inhibition and high koff values, the slightly
      modified PT70 leads to an ordered loop and a residence time of 24 minutes. To
      assess the structural differences of the complexes from a dynamic point of view,
      molecular dynamics (MD) simulations with a total sampling time of 3.0 us were
      performed for three ligand-bound and two ligand-free (perturbed) InhA systems.
      The individual simulations show comparable conformational features with respect
      to both the binding pocket and the SBL, allowing to define five recurring
      conformational families. Based on their different occurrence frequencies in the
      simulated systems, the conformational preferences could be linked to structural
      differences of the respective ligands to reveal important determinants of
      residence time. The most abundant conformation besides the stable EI* state is
      characterized by a shift of Ile202 and Val203 toward the hydrophobic pocket of
      InhA. The analyses revealed potential directions for avoiding this conformational
      change and, thus, hindering rapid dissociation: (1) an anchor group in 2'
      position of the B-ring for scaffold stabilization, (2) proper occupation of the
      hydrophobic pocket, and (3) the introduction of a barricade substituent in 5'
      position of the diphenyl ether B-ring. 

PMID- 25996599
TI  - Central retinal venous pressure in eyes of normal-tension glaucoma patients with
      optic disc hemorrhage.
AB  - OBJECTIVE: To compare central retinal venous pressure (CRVP) among eyes with and
      without optic disc hemorrhage (ODH) in bilateral normal-tension glaucoma (NTG)
      patients and NTG eyes without an episode of ODH. METHODS: In this prospective
      study, 22 bilateral NTG patients showing a unilateral ODH and 29 bilateral NTG
      patients without an episode of ODH were included. Eyes were categorized into
      group A (n = 22, eyes with ODH), group B (n = 22, fellow eyes without ODH), and
      group C (n = 29, NTG eyes without an episode of ODH). A contact lens
      ophthalmodynamometer was used to measure CRVP and central retinal arterial
      pressure (CRAP). RESULTS: Intraocular pressure (IOP) measured on the day of
      contact lens ophthalmodynamometry showed no difference among groups. However, the
      mean baseline IOP in group A was significantly lower than that in group C (P =
      .008). The CRVP in group A (29.1 +/- 10.8 mmHg) was significantly lower than that
      in group C (40.1 +/- 8.8 mmHg, P = .001), but similar to that in group B (30.5 +/
      8.7 mmHg, P = .409). A similar relationship was noted for CRAP. No significant
      eye-associated variable for ODH was found in group A and B by conditional
      logistic regression analysis (all P > 0.05). However, multivariate logistic
      regression analysis in groups A and C revealed that low mean baseline IOP (odds
      ratio [OR] = 0.69, 95% confidence interval [CI] 0.49-0.98, P = 0.043) and low
      CRVP (OR = 0.88, 95% CI 0.80-0.95, P = 0.003) were associated with ODH.
      CONCLUSIONS: CRVP was lower in NTG eyes with ODH than in eyes without an episode
      of ODH, but similar to that of fellow eyes without ODH. These imply less
      likelihood of association between increased central retinal venous resistance and
      ODH.

PMID- 25996600
TI  - Phytoestrogens and their metabolites in bulk-tank milk: effects of farm
      management and season.
AB  - Phytoestrogens have structures similar to endogenous steroids and may induce or
      inhibit the response of hormone receptors. The objectives of the present study
      were to compare the effects of long-term vs. short-term grassland management in
      organic and conventional dairy production systems, compare organic and
      conventional production systems and assess seasonal variation on phytoestrogen
      concentrations in bulk-tank milk. The concentrations of phytoestrogens were
      analyzed in bulk-tank milk sampled three times in two subsequent years from 28
      dairy farms: Fourteen organic (ORG) dairy farms with either short-term or long
      term grassland management were paired with 14 conventional (CON) farms with
      respect to grassland management. Grassland management varied in terms of time
      since establishment. Short-term grassland management (SG) was defined as
      establishment or reseeding every fourth year or more often, and long-term
      grassland management (LG) was defined as less frequent establishment or
      reseeding. The proportion of red clover (Trifolium pretense L.) in the herbage
      was positively correlated with milk concentrations of the mammalian isoflavone
      equol. Therefore, organically produced bulk-tank milk contained more equol than
      conventionally produced milk, and milk from ORG-SG farms had more equol than milk
      from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol
      than milk produced during the outdoor feeding period, because pastures contained
      less red clover than fields intended for silage production. Organically produced
      milk had also higher concentrations of the mammalian lignan enterolactone, but in
      contrast to equol, concentrations increased in the outdoor-feeding periods
      compared to the indoor-feeding periods. There were no indications of fertility
      problems on ORG-SG farms who had the highest red clover proportions in the
      herbage. This study shows that production system, grassland management, and
      season affect milk concentrations of phytoestrogens. However, compared to soy
      products, milk concentrations of phytoestrogens are low and future studies are
      required to investigate if the intake of phytoestrogens from dairy products has
      physiological effects in humans. 

PMID- 25996601
TI  - Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive
      Stage II/III Colorectal Cancer.
AB  - Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST)
      is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is
      caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We
      have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within
      DNA and subsequent cytotoxicity was most effective when both hMutSalpha (hMSH2
      hMSH6 heterodimer) and hMutSbeta (hMSH2-hMSH3 heterodimer) MMR complexes were
      present, compared to hMutSalpha > hMutSbeta alone. We tested if patients with
      EMAST CRCs (hMutSbeta defective) had diminished response to adjuvant 5-FU
      chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage
      II/III sporadic colorectal cancers for which we had 5-FU treatment and survival
      data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037,
      D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival
      curves were generated and multivariate analysis was used to determine
      contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients
      (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients
      was 51 months. Patients with EMAST CRCs demonstrated improved survival with
      adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We
      observed no difference in survival between patients with stage II/III EMAST and
      non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC
      patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The
      loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect
      patient outcome, contrasting patients whose tumors completely lack DNA MMR
      function (MSI-H). 

PMID- 25996602
TI  - Source Memory Rehabilitation: A Review Toward Recommendations for Setting Up a
      Strategy Training Aimed at the "What, Where, and When" of Episodic Retrieval.
AB  - Source memory is a core component of episodic recall as it allows for the
      reconstruction of contextual details characterizing the acquisition of episodic
      events. Unlike episodic memory, little is known about source memory
      rehabilitation. Our review addresses this issue by emphasizing several strategies
      as useful tools in source memory rehabilitation programs. Four main strategies
      are likely to improve source recall in amnesic patients-namely, (a) contextual
      cueing, (b) unitization, (c) errorless learning, and (d) executive function
      programs. The rationale behind our suggestion is that: (a) reinstating contextual
      cues during retrieval can serve as retrieval cues and enhance source memory; (b)
      unitization as an encoding process allows for the integration of several pieces
      of contextual information into a new single entity; (c) errorless learning may
      prevent patients from making errors during source learning; and (d) as source
      memory deteriorations have been classically attributed to executive dysfunction,
      the rehabilitation of the latter ability is likely to maintain the former
      ability. Besides these four strategies, our review suggests several additional
      rehabilitation techniques such as the vanishing cues and spaced retrieval
      methods. Another additional strategy is the use of electronic devices. By
      gathering these strategies, our review provides a helpful guideline for
      clinicians dealing with source memory impairments. Our review further highlights
      the lack of randomized and controlled studies in the field of source memory
      rehabilitation. 

PMID- 25996604
TI  - Separation of Binding Protein of Celangulin V from the Midgut of Mythimna
      separata Walker by Affinity Chromatography.
AB  - Celangulin V, an insecticidal compound isolated from the root bark of Chinese
      bittersweet, can affect the digestive system of insects. However, the mechanism
      of how Celangulin V induces a series of symptoms is still unknown. In this study,
      affinity chromatography was conducted through coupling of Celangulin V-6
      aminoacetic acid ester to the CNBr-activated Sepharose 4B. SDS-PAGE was used to
      analyze the collected fraction eluted by Celangulin V. Eight binding proteins
      (Zinc finger protein, Thioredoxin peroxidase (TPx), Glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH), SUMO E3 ligase RanBP2, Transmembrane protein 1, Actin, APN
      and V-ATPase) were obtained and identified by LC/Q-TOF-MS from the midgut of
      Mythimna separata larvae. The potential of these proteins to serve as target
      proteins involved in the insecticidal activity of Celangulin V is discussed.

PMID- 25996603
TI  - Different populations of blacklegged tick nymphs exhibit differences in questing
      behavior that have implications for human lyme disease risk.
AB  - Animal behavior can have profound effects on pathogen transmission and disease
      incidence. We studied the questing (= host-seeking) behavior of blacklegged tick
      (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the
      eastern United States. Lyme disease is common in northern but not in southern
      regions, and prior ecological studies have found that standard methods used to
      collect host-seeking nymphs in northern regions are unsuccessful in the south.
      This led us to hypothesize that there are behavior differences between northern
      and southern nymphs that alter how readily they are collected, and how likely
      they are to transmit the etiological agent of Lyme disease to humans. To examine
      this question, we compared the questing behavior of I. scapularis nymphs
      originating from one northern (Lyme disease endemic) and two southern (non
      endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and
      Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2
      arenas containing wooden dowels (mimicking stems of understory vegetation) for 10
      (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these
      stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was
      much greater for northern than for southern origin ticks in both years and at all
      field sites (19.5 times greater in 2011; 3.6-11.6 times greater in 2012). Our
      findings suggest that southern origin I. scapularis nymphs rarely emerge from the
      leaf litter, and consequently are unlikely to contact passing humans. We propose
      that this difference in questing behavior accounts for observed geographic
      differences in the efficacy of the standard sampling techniques used to collect
      questing nymphs. These findings also support our hypothesis that very low Lyme
      disease incidence in southern states is, in part, a consequence of the type of
      host-seeking behavior exhibited by southern populations of the key Lyme disease
      vector. 

PMID- 25996606
TI  - Recommended mass spectrometry-based strategies to identify botulinum neurotoxin
      containing samples.
AB  - Botulinum neurotoxins (BoNTs) cause the disease called botulism, which can be
      lethal. BoNTs are proteins secreted by some species of clostridia and are known
      to cause paralysis by interfering with nerve impulse transmission. Although the
      human lethal dose of BoNT is not accurately known, it is estimated to be between
      0.1 MUg to 70 MUg, so it is important to enable detection of small amounts of
      these toxins. Our laboratory previously reported on the development of Endopep
      MS, a mass-spectrometric-based endopeptidase method to detect, differentiate, and
      quantify BoNT immunoaffinity purified from complex matrices. In this work, we
      describe the application of Endopep-MS for the analysis of thirteen blinded
      samples supplied as part of the EQuATox proficiency test. This method
      successfully identified the presence or absence of BoNT in all thirteen samples
      and was able to successfully differentiate the serotype of BoNT present in the
      samples, which included matrices such as buffer, milk, meat extract, and serum.
      Furthermore, the method yielded quantitative results which had z-scores in the
      range of -3 to +3 for quantification of BoNT/A containing samples. These results
      indicate that Endopep-MS is an excellent technique for detection,
      differentiation, and quantification of BoNT in complex matrices.

PMID- 25996605
TI  - Toxins Targeting the Kv1.3 Channel: Potential Immunomodulators for Autoimmune
      Diseases.
AB  - Autoimmune diseases are usually accompanied by tissue injury caused by
      autoantigen-specific T-cells. KV1.3 channels participate in modulating calcium
      signaling to induce T-cell proliferation, immune activation and cytokine
      production. Effector memory T (TEM)-cells, which play major roles in many
      autoimmune diseases, are controlled by blocking KV1.3 channels on the membrane.
      Toxins derived from animal venoms have been found to selectively target a variety
      of ion channels, including KV1.3. By blocking the KV1.3 channel, these toxins are
      able to suppress the activation and proliferation of TEM cells and may improve
      TEM cell-mediated autoimmune diseases, such as multiple sclerosis and type I
      diabetes mellitus. 

PMID- 25996607
TI  - Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth.
AB  - We examined the thymoquinone induced inhibition of purified F1 or membrane bound
      F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were
      completely inhibited by thymoquinone with no residual ATPase activity. The
      process of inhibition was fully reversible and identical in both membrane bound
      F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of
      ATP synthase expressing wild-type E. coli cell growth and non-inhibition of
      ATPase gene deleted null control cells demonstrates that ATP synthase is a
      molecular target for thymoquinone. This also links the beneficial dietary based
      antimicrobial and anticancer effects of thymoquinone to its inhibitory action on
      ATP synthase. 

PMID- 25996610
TI  - Phase-transition properties of glycerol-dipalmitate lipid bilayers investigated
      using molecular dynamics simulation.
AB  - The phase- and phase-transition properties of glycerol-dipalmitate (GDP) bilayer
      patches are investigated using molecular dynamics simulations. This permits to
      characterize the influence of introducing a second aliphatic lipid tail by
      comparison to previously reported simulations of glycerol-1-monopalmitate (GMP).
      To this purpose, a set of 67 simulations (up to 300ns duration) of 2*8*8GDP
      bilayer patches are performed, considering the two GDP isomers glycerol-1,3
      dipalmitate (13GDP) and glycerol-1,2-dipalmitate (12GDP; racemic), two hydration
      levels (12GDP only), and temperatures in the range 250-370K. In agreement with
      experiment, the GDP simulations reveal an increase in the main transition
      temperature by about 25K relative to GMP, and the occurrence of non-bilayer
      phases at high temperatures (inverted-cylinder or stacked phases). Structurally,
      the GDP system tends to evidence a tighter packing of the chains, a reduced
      extent of tilting, increased order parameters and a reduced fluidity. These
      differences are easily interpreted in terms of two key changes in molecular
      properties when going from GMP to GDP: (i) the reduction of the headgroup
      polarity and hydration (from two free hydroxyl groups to a single one); (ii) the
      increase in the effective tail cross-section relative to the (hydrated) headgroup
      cross-section, conferring to GDP a particular wedge shape. These two effects
      contribute to the relative instability of the liquid-crystalline phase, the
      stability being recovered in nature when the diglyceride headgroup is
      functionalized by a bulky or/and polar substituent. 

PMID- 25996608
TI  - Structural comparison of four different antibodies interacting with human
      papillomavirus 16 and mechanisms of neutralization.
AB  - Cryo-electron microscopy (cryo-EM) was used to solve the structures of human
      papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from
      three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2.
      The structure-function analysis revealed predominantly monovalent binding of each
      Fab with capsid interactions that involved multiple loops from symmetry related
      copies of the major capsid protein. The residues identified in each Fab-virus
      interface map to a conformational groove on the surface of the capsomer. In
      addition to the known involvement of the FG and HI loops, the DE loop was also
      found to constitute the core of each epitope. Surprisingly, the epitope mapping
      also identified minor contributions by EF and BC loops. Complementary
      immunological assays included mAb and Fab neutralization. The specific binding
      characteristics of mAbs correlated with different neutralizing behaviors in pre-
      and post-attachment neutralization assays. 

PMID- 25996609
TI  - Spontaneous Post-Transplant Disorders in NOD.Cg- Prkdcscid Il2rgtm1Sug/JicTac
      (NOG) Mice Engrafted with Patient-Derived Metastatic Melanomas.
AB  - Patient-derived tumor xenograft (PDTX) approach is nowadays considered a reliable
      preclinical model to study in vivo cancer biology and therapeutic response. NOD
      scid and Il2rg-deficient mice represent the "gold standard" host for the
      generation of PDTXs. Compared to other immunocompromised murine lines, these mice
      offers several advantages including higher engraftment rate, longer lifespan and
      improved morphological and molecular preservation of patient-derived neoplasms.
      Here we describe a spectrum of previously uncharacterized post-transplant
      disorders affecting 14/116 (12%) NOD.Cg- Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice
      subcutaneously engrafted with patient-derived metastatic melanomas. Affected mice
      exhibited extensive scaling/crusting dermatitis (13/14) associated with
      emaciation (13/14) and poor/unsuccessful tumor engraftment (14/14). In this
      context, the following pathological conditions have been recognized and
      characterized in details: (i) immunoinflammatory disorders with features of graft
      versus host disease (14/14); (ii) reactive lymphoid infiltrates effacing
      xenografted tumors (8/14); (iii) post-transplant B cell lymphomas associated with
      Epstein-Barr virus reactivation (2/14). We demonstrate that all these entities
      are driven by co-transplanted human immune cells populating patient-derived tumor
      samples. Since the exploding interest in the utilization of NOD scid and Il2rg
      deficient mice for the establishment of PDTX platforms, it is of uppermost
      importance to raise the awareness of the limitations associated with this model.
      The disorders here described adversely impact tumor engraftment rate and animal
      lifespan, potentially representing a major confounding factor in the context of
      efficacy and personalized therapy studies. The occurrence of these conditions in
      the NOG model reflects the ability of this mouse line to promote efficient
      engraftment of human immune cells. Co-transplanted human lymphoid cells have
      indeed the potential to colonize the recipient mouse initiating the post
      transplant conditions here reported. On the other hand, the evidence of an immune
      response of human origin against the xenotransplanted melanoma opens intriguing
      perspectives for the establishment of suitable preclinical models of anti
      melanoma immunotherapy. 

PMID- 25996611
TI  - Comparative analysis of selected scales to assess prognosis in acute
      pancreatitis.
AB  - OBJECTIVE: To evaluate the utility of selected scales to prognosticate the
      severity and risk for death among patients with acute pancreatitis (AP) according
      to the revised Atlanta classification published in 2012. METHODS: Prospective
      data regarding patients hospitalized due to AP were analyzed. The final analysis
      included a total of 1014 patients. The bedside index for severity in acute
      pancreatitis (BISAP), Panc 3 scores and Ranson scales were calculated using data
      from the first 24 h of admission. RESULTS: Mild AP was diagnosed in 822 (81.1%)
      cases, moderate in 122 (12%) and severe in 70 (6.9%); 38 (3.7%) patients died.
      The main causes of AP were cholelithiasis (34%) and alcohol abuse (26.7%).
      Recurrence of AP was observed in 244 (24.1%) patients. In prognosticating the
      severity of AP, the most useful scale proved to be the Acute Physiology and
      Chronic Health Evaluation (APACHE) II (area under the curve [AUC] 0.724 [95% CI
      0.655 to 0.793]), followed by BISAP (AUC 0.693 [95% CI 0.622 to 0.763]). In
      prognosticating a moderate versus mild course of AP, the CT severity index proved
      to be the most decisive (AUC 0.819 [95% CI 0.767 to 0.871]). Regarding prognosis
      for death, APACHE II had the highest predictive value (AUC 0.726 [95% CI 0.621 to
      0.83]); however, a similar sensitivity was observed using the BISAP scale (AUC
      0.707 [95% CI 0.618 to 0.797]). CONCLUSIONS: Scoring systems used in
      prognosticating the course of the disease vary with regard to sensitivity and
      specificity. The CT severity index scoring system showed the highest precision in
      prognosticating moderately severe AP (as per the revised Atlanta criteria, 2012);
      however, in prognosticating a severe course of disease and mortality, APACHE II
      proved to have the greatest predictive value.

PMID- 25996612
TI  - Adenoma detection rates decline with increasing procedural hours in an
      endoscopist's workload.
AB  - BACKGROUND: Operator fatigue may negatively influence adenoma detection (AD)
      during screening colonoscopy. OBJECTIVE: To better characterize factors affecting
      AD, including the number of hours worked, and the number and type of procedures
      performed before an index screening colonoscopy. METHODS: A retrospective cohort
      study was conducted involving individuals undergoing a screening colonoscopy at a
      major tertiary care hospital in Montreal, Quebec. Individuals were identified
      using an endoscopic reporting database; AD was identified by an electronic chart
      review. A hierarchical logistic regression analysis was performed to determine
      the association between patient- and endoscopist-related variables and AD.
      RESULTS: A total of 430 consecutive colonoscopies performed by 10
      gastroenterologists and two surgeons were included. Patient mean (+/- SD) age was
      63.4+/-10.9 years, 56.3% were males, 27.7% had undergone a previous colonoscopy
      and the cecal intubation rate was 95.7%. The overall AD rate was 25.7%. Age was
      associated with AD (OR 1.06 [95% CI 1.03 to 1.08]), while female sex (OR 0.44
      [95% CI 0.25 to 0.75]), an indication for average-risk screening (OR 0.47 [95% CI
      0.27 to 0.80]) and an increase in the number of hours during which endoscopies
      were performed before the index colonoscopy (OR 0.87 [95% CI 0.76 to 0.99]) were
      associated with lower AD rates. On exploratory univariable analysis, a threshold
      of 3 h of endoscopy time performed before the index colonoscopy was associated
      with decreased AD. CONCLUSION: The number of hours devoted to endoscopies before
      the index colonoscopy was inversely associated with AD rate, with decreased
      performance possibly as early as within 3 h. This metric should be confirmed in
      future studies and considered when optimizing scheduling practices.

PMID- 25996613
TI  - Resident trainees do not affect patient satisfaction in an outpatient
      gastroenterology clinic: a prospective study conducted in a Canadian
      gastroenterology clinic.
AB  - BACKGROUND: There is little literature regarding how a gastroenterology trainee
      affects a patient's interpretation of care during outpatient clinic visits.
      Improving patient satisfaction is desirable and benefits may include enhanced
      patient compliance as well as providing trainees with areas for improvement.
      OBJECTIVES: To evaluate patient satisfaction in an outpatient gastroenterology
      clinic when seen by a trainee and attending physician versus an attending
      physician alone. The secondary objective was to evaluate physician
      characteristics that play a role in creating a positive clinical experience.
      METHODS: A randomized prospective survey study was conducted over an 11-month
      period (July 2012 to June 2013) at St Boniface Hospital (Winnipeg, Manitoba). Two
      gastroenterology fellows (postgraduate year 4 and 5) and nine internal medicine
      residents (postgraduate year 1 to 3) comprised the 'trainee' role, while three
      academic clinicians comprised the 'attending' role. Patients included individuals
      seen for an initial consultation and were >18 years of age. RESULTS: A total of
      211 patients comprised the final study group, with 118 in the attending group and
      93 in the trainee group. In univariate analysis, patients more often had a very
      good experience when seen by an attending physician alone versus a trainee and
      attending physician (73% versus 56%; P=0.016); however, on multivariate analysis,
      there was no significant difference in patient satisfaction (OR 0.89; P=0.931).
      Physician factors found to be associated with high patient satisfaction on
      multivariate analysis included: addressing all patient concerns (OR 27.56;
      P=0.021); giving the patient a preliminary diagnosis (OR 78.02; P=0.006); and
      feeling the physician was thorough (OR 72.53; P=0.029). CONCLUSIONS: The present
      study did not reveal a difference in patient satisfaction if a patient sees an
      attending physician alone or with a trainee. Moreover, to improve patient
      satisfaction in a gastroenterology clinic, physicians should address all patient
      concerns, provide a preliminary diagnosis and appear to be thorough in their
      assessment. Further work to increase patient awareness on the role of residents
      in teaching hospitals is warranted to further promote careers in
      gastroenterology.

PMID- 25996614
TI  - Mild clinical behaviour of Crohn disease in elderly patients in a Latin American
      country: A case-control study.
AB  - BACKGROUND: Crohn disease is characterized by fluctuating clinical behaviour,
      which is influenced by various factors. There are no data from Latin America that
      evaluate the clinical behaviour of Crohn disease in elderly patients. OBJECTIVE:
      To evaluate the clinical course of elderly onset Crohn disease compared with
      younger onset in the Mexican population. METHODS: The present analysis was a case
      control study that included 132 patients with a histopathological diagnosis of
      Crohn disease between 1983 and 2013 in an inflammatory bowel disease clinic of a
      tertiary care centre. Statistical analysis was performed using SPSS version 17
      (IBM Corporation, USA) and descriptive statistics, chi2 and Fisher's exact test
      for categorical variables and Student's t test for numerical variables.
      Univariate and multivariate analysis were performed to identify associated risk
      factors and OR was calculated. RESULTS: A total of 132 patients (73 men and 59
      women) were divided into two groups according to age at diagnosis: 27 cases (>60
      years of age) and 105 controls (<=60 years of age). Factors influencing the
      clinical course of Crohn disease in the elderly were: female sex (OR 2.55 [95% CI
      1.06 to 6.10]; P=0.02); colonic location (OR 0.22 [95% CI 0.03 to 0.89]; P=0.02);
      mild clinical behaviour of disease (OR 10.08 [95% CI 3.74 to 27.17]; P=0.0001);
      response to medical treatment (OR 2.85 [95% CI 1.08 to 7.48]; P=0.02); frequent
      use of sulfasalazine (OR 4.46 [95% CI 1.22 to 16.28]; P=0.03); less use of
      azathioprine (OR 0.38 [95% CI 0.13 to 1.03]; P=0.04); and long-term remission (OR
      4.96 [95% CI 1.70 to 14.48]; P=0.002). CONLCUSION: Elderly patients with Crohn
      disease had a mild clinical course characterized by the lack of escalation to
      immunosuppressive and anti-tumour necrosis factor therapy, as well as long-term
      remission.

PMID- 25996616
TI  - pH-Triggered Controllable Release of Silver-Indole-3 Acetic Acid Complexes from
      Mesoporous Silica Nanoparticles (IBN-4) for Effectively Killing Malignant
      Bacteria.
AB  - An efficient approach for the antimicrobial agent delivery specifically at acidic
      pH has been proposed. At the outset, functionalized mesoporous nanoparticles
      (NPs) were examined to verify the success of synthesis while considering the
      structural properties by various characterizations. The NPs were immobilized with
      silver-indole-3 acetic acid hydrazide (IAAH-Ag) complexes via a pH-sensitive
      hydrazone bond, which functioned as a model drug. When the transitional metal
      complexes with IBN-4-IAAH-Ag were exposed to acidic pH (near pH 5.0), the silver
      ions were preferentially released (70%) in a controlled manner up to 12 h by pH
      sensitive denial of hydrazone bonds. In contrary, a low drug release (about 25%)
      was seen in physiological buffer (pH 7.4) demonstrating the pH sensitive release
      of this drug. Furthermore, the antibacterial efficacy of this unique structured
      sample was tested against the planktonic cells and biofilms of Gram-positive and
      Gram-negative bacteria with field emission scanning electron microscope in turn
      measuring the growth curves, formation of lethal reactive oxygen species, protein
      leakage, and DNA damage. The synthesized pH-sensitive IAAH-Ag complex was found
      to have high antimicrobial efficacy against multidrug resistant clinical isolates
      both in planktonic and biofilm states. Going forward, the synthesized
      nanoconjugates proved a good in vivo efficacy in treating the bacterial infection
      of mice. These new metal complex-conjugated NPs through a pH-sensitive hydrazone
      bond opened up a new avenue for the design and synthesis of the next generation
      antibacterial agents, which would act as an alternative to antibiotics. 

PMID- 25996615
TI  - Transperineal ultrasonography in perianal Crohn disease: A valuable imaging
      modality.
AB  - Aims of treatment for Crohn disease have moved beyond the resolution of clinical
      symptoms to objective end points including endoscopic and radiological normality.
      Regular re-evaluation of disease status to safely, readily and reliably detect
      the presence of inflammation and complications is paramount. Improvements in
      sonographic technology over recent years have facilitated a growing enthusiasm
      among radiologists and gastroenterologists in the use of ultrasound for the
      assessment of inflammatory bowel disease. Transabdominal intestinal ultrasound is
      accurate, affordable and safe for the assessment of luminal inflammation and
      complications in Crohn disease, and can be performed with or without the use of
      intravenous contrast enhancement. Perianal fistulizing disease is a common,
      complex and often treatment-refractory complication of Crohn disease, which
      requires regular radiological monitoring. Endoanal ultrasound is invasive,
      uncomfortable and yields limited assessment of the perineal region. Although
      magnetic resonance imaging of the pelvis is established, timely access may be a
      problem. Transperineal ultrasound has been described in small studies, and is an
      accurate, painless and cost-effective method for documenting perianal fluid
      collections, fistulas and sinus tracts. In the present article, the authors
      review the literature regarding perineal ultrasound for the assessment of
      perianal Crohn disease and use case examples to illustrate its clinical utility. 

PMID- 25996617
TI  - Measurement of resistant starch content in cooked rice and analysis of
      gelatinization and retrogradation characteristics.
AB  - Digestion-resistant starch (RS) has many physiologic functions. The RS content is
      measured by enzymatically degrading flour samples according to the method of the
      Association of Official Analytical Chemists. Experiments have been performed with
      wheat, corn, and other grains, but there are no data for cooked rice grains in
      the form ingested by humans. Thus, we investigated a method to measure RS that is
      suitable for cooked rice grains using rice cultivars that are reported to
      differentially increase postprandial blood glucose in humans. Using a method for
      cooking individual rice grains and optimized enzyme reaction conditions, we
      established an RS measurement method. We also found that the amylopectin crystal
      condition affects the RS content measured using our method. 

PMID- 25996618
TI  - Detection of Peptide-based nanoparticles in blood plasma by ELISA.
AB  - AIMS: The aim of the current study was to develop a method to detect peptide
      linked nanoparticles in blood plasma. MATERIALS & METHODS: A convenient enzyme
      linked immunosorbent assay (ELISA) was developed for the detection of peptides
      functionalized with biotin and fluorescein groups. As a proof of principle,
      polymerized pentafluorophenyl methacrylate nanoparticles linked to biotin
      carboxyfluorescein labeled peptides were intravenously injected in Wistar rats.
      Serial blood plasma samples were analyzed by ELISA and by liquid chromatography
      mass spectrometry (LC/MS) technology. RESULTS: The ELISA based method for the
      detection of FITC labeled peptides had a detection limit of 1 ng/mL. We were able
      to accurately measure peptides bound to pentafluorophenyl methacrylate
      nanoparticles in blood plasma of rats, and similar results were obtained by
      LC/MS. CONCLUSIONS: We detected FITC-labeled peptides on pentafluorophenyl
      methacrylate nanoparticles after injection in vivo. This method can be extended
      to detect nanoparticles with different chemical compositions.

PMID- 25996619
TI  - High Rates of Asymptomatic, Sub-microscopic Plasmodium vivax Infection and
      Disappearing Plasmodium falciparum Malaria in an Area of Low Transmission in
      Solomon Islands.
AB  - INTRODUCTION: Solomon Islands is intensifying national efforts to achieve malaria
      elimination. A long history of indoor spraying with residual insecticides,
      combined recently with distribution of long lasting insecticidal nets and
      artemether-lumefantrine therapy, has been implemented in Solomon Islands. The
      impact of these interventions on local endemicity of Plasmodium spp. is unknown.
      METHODS: In 2012, a cross-sectional survey of 3501 residents of all ages was
      conducted in Ngella, Central Islands Province, Solomon Islands. Prevalence of
      Plasmodium falciparum, P. vivax, P. ovale and P. malariae was assessed by
      quantitative PCR (qPCR) and light microscopy (LM). Presence of gametocytes was
      determined by reverse transcription quantitative PCR (RT-qPCR). RESULTS: By qPCR,
      468 Plasmodium spp. infections were detected (prevalence = 13.4%; 463 P. vivax,
      five mixed P. falciparum/P. vivax, no P. ovale or P. malariae) versus 130 by LM
      (prevalence = 3.7%; 126 P. vivax, three P. falciparum and one P. falciparum/P.
      vivax). The prevalence of P. vivax infection varied significantly among villages
      (range 3.0-38.5%, p<0.001) and across age groups (5.3-25.9%, p<0.001). Of 468 P.
      vivax infections, 72.9% were sub-microscopic, 84.5% afebrile and 60.0% were both
      sub-microscopic and afebrile. Local residency, low education level of the
      household head and living in a household with at least one other P. vivax
      infected individual increased the risk of P. vivax infection. Overall, 23.5% of
      P. vivax infections had concurrent gametocytaemia. Of all P. vivax positive
      samples, 29.2% were polyclonal by MS16 and msp1F3 genotyping. All five P.
      falciparum infections were detected in residents of the same village, carried the
      same msp2 allele and four were positive for P. falciparum gametocytes.
      CONCLUSION: P. vivax infection remains endemic in Ngella, with the majority of
      cases afebrile and below the detection limit of LM. P. falciparum has nearly
      disappeared, but the risk of re-introductions and outbreaks due to travel to
      nearby islands with higher malaria endemicity remains.

PMID- 25996620
TI  - Comparison of clinical prediction models for resistant bacteria in community
      onset pneumonia.
AB  - OBJECTIVES: Six recently published algorithms classify pneumonia patients
      presenting from the community into high- and low-risk groups for resistant
      bacteria. Our objective was to compare performance of these algorithms for
      identifying patients infected with bacteria resistant to traditional community
      acquired pneumonia antibiotics. METHODS: This was a retrospective study of
      consecutive adult patients diagnosed with pneumonia in an emergency department
      and subsequently hospitalized. Each patient was classified as high or low risk
      for resistant bacteria according to the following algorithms: original health
      care-associated pneumonia (HCAP) criteria, Summit criteria, Brito and Niederman
      strategy, Shorr model, Aliberti model, and Shindo model. The reference for
      comparison was detection of resistant bacteria, defined as methicillin-resistant
      Staphylococcus aureus or Gram-negative bacteria resistant to ceftriaxone or
      levofloxacin. RESULTS: A total of 614 patients were studied, including 36 (5.9%)
      with resistant bacteria. The HCAP criteria classified 304 (49.5%) patients as
      high risk, with an area under the receiver operating characteristic curve (AUC)
      of 0.63 (95% confidence interval [CI] = 0.54 to 0.72), sensitivity of 0.69 (95%
      CI = 0.52 to 0.83), and specificity of 0.52 (95% CI = 0.48 to 0.56). None of the
      other algorithms improved both sensitivity and specificity or significantly
      improved the AUC. Compared to the HCAP criteria, the Shorr and Aliberti models
      classified more patients as high risk, resulting in higher sensitivity and lower
      specificity. The Shindo model classified fewer patients as high risk, with lower
      sensitivity and higher specificity. CONCLUSIONS: All algorithms for
      identification of resistant bacteria included in this study had suboptimal
      performance to guide antibiotic selection. New strategies for selecting empirical
      antibiotics for community-onset pneumonia are necessary.

PMID- 25996621
TI  - The Development and Use of Evidence Summaries for Point of Care Information
      Systems: A Streamlined Rapid Review Approach.
AB  - BACKGROUND: A systematic review of evidence is the research method which
      underpins the traditional approach to evidence-based health care. As systematic
      reviews follow a rigorous methodology, they can take a substantial amount of time
      to complete ranging in duration from 6 months to 2 years. Rapid reviews have been
      proposed as a method to provide summaries of the literature in a more timely
      fashion. AIM: The aim of this paper is to outline our experience of developing
      evidence summaries in the context of a point of care resource as a contribution
      to the emerging field of rapid review methodologies. METHODS: Evidence summaries
      are defined as a synopsis that summarizes existing international evidence on
      healthcare interventions or activities. These summaries are based on structured
      searches of the literature and selected evidence-based healthcare databases.
      Following the search, all studies are assessed for internal validity using an
      abridged set of critical appraisal tools. Once developed, they undergo three
      levels of peer review by internal and external experts. RESULTS: As of November
      2014, there are 2458 evidence summaries that have been created across a range of
      conditions to inform evidence-based healthcare practices. In addition, there is
      ongoing development of various new evidence summaries on a wide range of topics.
      Approximately 60-70 new evidence summaries are published every month, covering
      research in various medical specialty areas. All summaries are updated annually.
      LINKING EVIDENCE TO ACTION: Systematic reviews, although the ideal type of
      research to inform practice, often do not meet the needs of users at the point of
      care. This article describes the development framework for the creation of
      evidence summaries, a type of rapid review. Although evidence summaries may
      result in a less rigorous process of development, they can be useful for
      improving practice at the point of care.

PMID- 25996622
TI  - Bioleaching mechanism of Zn, Pb, In, Ag, Cd and As from Pb/Zn smelting slag by
      autotrophic bacteria.
AB  - A few studies have focused on release of valuable/toxic metals from Pb/Zn
      smelting slag by heterotrophic bioleaching using expensive yeast extract as an
      energy source. The high leaching cost greatly limits the practical potential of
      the method. In this work, autotrophic bioleaching using cheap sulfur or/and
      pyrite as energy matter was firstly applied to tackle the smelting slag and the
      bioleaching mechanisms were explained. The results indicated autotrophic
      bioleaching can solubilize valuable/toxic metals from slag, yielding maximum
      extraction efficiencies of 90% for Zn, 86% for Cd and 71% for In, although the
      extraction efficiencies of Pb, As and Ag were poor. The bioleaching performance
      of Zn, Cd and Pb was independent of leaching system, and leaching mechanism was
      acid dissolution. A maximum efficiency of 25% for As was achieved by acid
      dissolution in sulfursulfur oxidizing bacteria (S-SOB), but the formation of
      FeAsO4 reduced extraction efficiency in mixed energy source - mixed culture (MS
      MC). Combined works of acid dissolution and Fe(3+) oxidation in MS-MC was
      responsible for the highest extraction efficiency of 71% for In. Ag was present
      in the slag as refractory AgPb4(AsO4)3 and AgFe2S3, so extraction did not occur. 

PMID- 25996623
TI  - Lab-assay for estimating methane emissions from deep-pit swine manure storages.
AB  - Methane emission is an important tool in the evaluation of manure management
      systems due to the potential impact it has on global climate change. Field
      procedures used for estimating methane emission rates require expensive
      equipment, are time consuming, and highly variable between farms. The purpose of
      this paper is to report a simple laboratory procedure for estimating methane
      emission from stored manure. The test developed was termed a methane production
      rate (MPR) assay as it provides a short-term biogas production measurement. The
      MPR assay incubation time is short (3d), requires no sample preparation in terms
      of inoculation or dilution of manure, is incubated at room temperature, and the
      manure is kept stationary. These conditions allow for high throughput of samples
      and were chosen to replicate the conditions within deep-pit manure storages. In
      brief, an unaltered aliquot of manure was incubated at room temperature for a
      three-days to assay the current rate of methane being generated by the manure.
      The results from this assay predict an average methane emission factor of 12.2 +/
      8.1 kg CH4 head(-1) yr(-1) per year, or about 5.5 +/- 3.7 kg CH4 per finished
      animal, both of which compare well to literature values of 5.5 +/- 1.1 kg CH4 per
      finished pig for deep-pit systems (Liu et al., 2013). The average methane flux
      across all sites and months was estimated to be 22 +/- 17 mg CH4 m(-2)-min(-1),
      which is within literature values for deep-pit systems ranging from 0.24 to 63 mg
      CH4 m(-2)-min(-1) (Park et al., 2006) and similar to the 15 mg CH4 m(-2)-min(-1)
      estimated by (Zahn et al., 2001).

PMID- 25996624
TI  - Control of household mycoflora in fermented sausages using phenolic fractions
      from olive mill wastewaters.
AB  - Biopreservation using polyphenols represents an alternative to chemical molecules
      for improving food safety. In this work, we evaluated the antifungal activity of
      polyphenols extracted from olive mill wastewater (OMWWP) to reduce or eliminate
      the growth of undesired fungi on the surface of dry fermented sausages.
      Antagonism against Penicillium expansum DSMZ 1282, Penicillium verrucosum DSMZ
      12639, Penicillium nalgiovense MS01, Aspergillus ochraceus DSMZ 63304,
      Cladosporium cladosporioides MS12, and Eurotium amstelodami MS10 was evident at
      1.25% OMWWP in vitro, whereas in situ application of 2.5% OMWWP strongly reduced
      undesired household fungal species such as C. cladosporioides, Penicillium
      aurantiogriseum, Penicillium commune, and Eurotium amstelodami, while a moderate
      antagonistic activity towards P. nalgiovense and Penicillium chrysogenum was
      observed at the same concentration. OMWWP at the concentrations used in this
      study demonstrated species-dependent antifungal activity by inhibiting both
      fungal growth and spore germination. Therefore, OMWWP can be regarded as a
      potential alternative to synthetic antifungal compounds to preserve the product
      from both oxidation and undesired fungi, without changing the sensory
      characteristics. 

PMID- 25996625
TI  - Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere
      length.
AB  - Studies of the effects of smoking on leukocyte telomere length (LTL) using
      cigarettes smoked per day or pack years smoked (PYS) present limitations.
      Reported high levels of smoking may not increase toxin exposure levels
      proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff
      volume and overall exposure based on total N-nitrosamines, is highly reproducible
      and independent of time since the last cigarette. We hypothesized that smokers
      with higher NMRs will exhibit increased total puff volume, reflecting efforts to
      extract more nicotine from their cigarettes and increasing toxin exposure. In
      addition, higher levels of smoking could cause a gross damage in LTL. The urinary
      cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a
      LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood
      samples. We found a significant association between NMR and CYP2A6 genotype.
      Reduction in LTL was seen in relation to accumulated tobacco consumption and
      years smoking when we adjusted for age and gender. However, there were no
      significant differences between NMR values and LTL. In our study the higher
      exposure was associated with lower number of PYS. Smokers with reduced cigarette
      consumption may exhibit compensatory smoking behavior that results in no reduced
      tobacco toxin exposure. Our results suggest that lifetime accumulated smoking
      exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless,
      a combination of smoking topography (NMR) and consumption (PYS) measures may
      provide useful information about smoking effects on health outcomes. 

PMID- 25996626
TI  - Urinary metabolites of polycyclic aromatic hydrocarbons in Saudi Arabian
      schoolchildren in relation to sources of exposure.
AB  - Polycyclic aromatic hydrocarbons contain a number of known carcinogenic
      compounds, and urinary biomarkers have been widely used as a measure of exposure
      but quantitative relationships with exposure variables have proved elusive. This
      study aimed to quantify the relationship between exposures to phenanthrene and
      pyrene from atmospheric and dietary sources with the excretion of 1-hydroxypyrene
      and hydroxyphenanthrenes in urine as biomarkers of exposure. The study population
      consisted of 204 male schoolchildren attending three schools in different parts
      of Jeddah, Saudi Arabia who provided urine samples on each of three consecutive
      days. Outdoor air measurements of polycyclic aromatic hydrocarbons were made at
      the schools and the children provided information on diet, exposure to
      environmental tobacco smoke and incense, and various lifestyle factors through a
      questionnaire. Mixed models with random effects for subjects nested within site
      were fitted in order to examine the relationship between exposure variables and
      urinary PAH metabolites. A unit increase (1 ng m(-3)) in ambient pyrene
      (particulate plus gaseous phase) was associated with a 3.5% (95% CI: 1.01%,
      5.13%) increase in urinary 1-hydroxypyrene concentration. A unit increase in
      ambient phenanthrene was associated with a 1.01% (95% CI: 0.03%, 2.02%) increase
      in total hydroxyphenanthrene concentrations. Consumption of chargrilled food
      increased the 1-hydroxypyrene and hydroxyphenanthrene concentrations by 24% (95%
      CI: 11%, 37%) and 17% (95% CI: 8%, 26%) respectively. We did not find evidence of
      association for environmental tobacco smoke exposure or incense burning. It is
      concluded that both respiratory exposure and consumption of chargrilled food are
      considerable sources of PAH exposure in this population as reflected by
      concentrations of urinary biomarkers.

PMID- 25996627
TI  - Can a workbook work? Examining whether a practitioner evaluation toolkit can
      promote instrumental use.
AB  - In large-scale, multi-site contexts, developing and disseminating practitioner
      oriented evaluation toolkits are an increasingly common strategy for building
      evaluation capacity. Toolkits explain the evaluation process, present evaluation
      design choices, and offer step-by-step guidance to practitioners. To date, there
      has been limited research on whether such resources truly foster the successful
      design, implementation, and use of evaluation findings. In this paper, we
      describe a multi-site project in which we developed a practitioner evaluation
      toolkit and then studied the extent to which the toolkit and accompanying
      technical assistance was effective in promoting successful completion of local
      level evaluations and fostering instrumental use of the findings (i.e., whether
      programs directly used their findings to improve practice, see Patton, 2008).
      Forensic nurse practitioners from six geographically dispersed service programs
      completed methodologically rigorous evaluations; furthermore, all six programs
      used the findings to create programmatic and community-level changes to improve
      local practice. Implications for evaluation capacity building are discussed. 

PMID- 25996628
TI  - "Baby? Baby Not?": Exploring Women's Narratives About Ambivalence Towards an
      Unintended Pregnancy.
AB  - Unintended pregnancy among adult women is a significant public health challenge
      in the United States. Research has identified ambivalence as a risk factor for
      not using contraceptives. The qualitative study presented here examined women's
      narratives about ambivalence toward unintended pregnancy. In-depth interviews
      were conducted in 2012 with 28 women aged 20-45 years old who were recruited
      primarily via flyers in family planning clinics in a rural, Midwestern state. The
      interviews were coded for salient themes. Almost 40 percent of the women said
      that they had experienced an unintended pregnancy. All but two women expressed
      ambivalence, stating that they had both good and bad feelings about getting
      pregnant unintentionally. Women expressed if a pregnancy did occur, they would
      just have to step up and "deal with it." They recognized a baby was something
      special but not without negative aspects. Those who were less ambivalent (and
      more negative) had compelling reasons why, but even those women expressed some
      positive feelings. At times, ambivalence was expressed by negative reactions
      about having a child that coincided with believing that becoming a parent or
      having another child would have a positive impact on themselves. This study
      provides an examination of women's narratives about ambivalence toward pregnancy.
      Overall, women's narratives constructed ambivalence as arising from both positive
      and negative emotions, as well as beliefs about costs and benefits, associated
      with unintended pregnancy. Given its association with a lack of contraceptive
      use, understanding the components of ambivalence (e.g., feelings, beliefs) is
      important to bolstering interventions aimed toward decreasing ambivalence and
      increasing contraceptive use. 

PMID- 25996630
TI  - Application of Design Expert for the investigation of capsaicin-loaded
      microemulsions for transdermal delivery.
AB  - Our previous study reported that the Design Expert(r) Software showed a
      beneficial role in the development of microemulsions (ME) for transdermal drug
      delivery. To fully confirm the reproducibility and the reliability of
      simultaneous optimal ME formulations, the optimal ME formulations predicted by
      the Design Expert(r) Software were experimentally formulated and verified for
      their skin permeability. Ternary phase diagrams were used to predict the optimal
      ME area, and the ME formulations selected from outside this area were considered
      as candidate ME systems. Our ME systems were formulated with isopropyl myristate
      (IPM) as the oil phase, cocamide diethanolamine (DEA) as the surfactant, ethanol
      as a co-surfactant and water as the aqueous phase. The droplet size, size
      distribution, electrical conductivity, pH, drug content and skin permeability of
      the candidate ME systems were monitored. Our findings indicated that the skin
      permeability of the optimal ME and all of the candidate ME formulations was
      significantly greater than that of the commercial capsaicin (CAP) product. Our
      study succeeded in predicting and developing the ME systems for the transdermal
      delivery of CAP. The simplex lattice design used in this study is experimentally
      useful for the development of pharmaceutical formulations. 

PMID- 25996629
TI  - HIV therapeutic vaccines: moving towards a functional cure.
AB  - Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and
      SIV replication during chronic infection. However, these infections are rarely
      controlled by the host immune response, and most infected individuals need
      lifelong antiretroviral therapy (ART). Recent advances in our understanding of
      how anti-HIV immune responses are elicited and regulated prompted a surge of
      interest in harnessing these responses to reduce the HIV 'residual disease' that
      is present in ART-treated HIV-infected individuals. Novel approaches that are
      currently explored include both conventional therapeutic vaccines (i.e., active
      immunization strategies using HIV-derived immunogens) as well as the use of
      checkpoint blockers such as anti-PD-1 antibodies. These approaches appear
      promising as key components of complex therapeutic strategies aimed at curing HIV
      infection. 

PMID- 25996631
TI  - Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of
      cinnarizine: preparation, optimization, ex-vivo histopathological safety
      assessment and mucosal confocal imaging.
AB  - To circumvent the low and erratic absorption of orally administrated cinnarizine
      (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes
      (ufasomes) and encapsulating CN were prepared from oleic acid using a simple
      assembling strategy. The effects of varying drug concentration and cholesterol
      percentage on ufasomes size, polydispersity index and entrapment efficiency were
      investigated using 3(1)4(1) full factorial design. The optimized ufasomes that
      contained 14% cholesterol relative to oleic acid displayed spherical morphology
      with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the
      colloidal instability of CN-loaded ufasomes dispersions and their short residence
      time in the nasal cavity, the ufasomes were incorporated into mucoadhesive
      hydrogels that were lyophilized into unit dosage forms for accurate dosing.
      Scanning electron micrographs of the lyophilized gel revealed that the included
      ufasomes were intact, non-aggregating and maintained their spherical morphology.
      Rheological characterization of reconstituted ufasomal lyophilized gel ensured
      ease of application. Furthermore, the gel induced minor histopathological
      alterations in sheeps' nasal mucosa. Ex-vivo confocal laser imaging confirmed the
      ability of ufasomes to penetrate deep through nasal mucosa layers. The results
      highlighted in the current work confirm the feasibility of using CN-loaded
      ufasomal gels for intranasal drug delivery. 

PMID- 25996632
TI  - Hot-stage microscopy for determination of API fragmentation: comparison with
      other methods.
AB  - Although the fragmentation of the active pharmaceutical ingredient (API) is a
      phenomenon that is mentioned in many literature sources, no well-suited
      analytical tools for its investigation are currently known. We used the hot-stage
      microscopy method, already presented in our previous work, and studied the real
      fragmentation of the tadalafil particles in model tablets which were prepared
      under different compaction pressures. The morphology, spectral imaging and
      evaluation of plastic and elastic energies were also analyzed to support the hot
      stage method. The prepared blend of tadalafil and excipients was compacted under
      a several forces from 5 to 35 kN to reveal the trend of fragmentation. The exact
      fragmentation of tadalafil with increased compaction pressure was revealed by the
      hot-stage microscopic method and it was in good agreement with plastic and
      elastic energies. Conversely, spectral imaging, which is being used for this
      analysis, was considered to be inaccurate methodology as mainly agglomerates, not
      individual particles, were measured. The availability of the hot-stage
      microscopic method equips pharmaceutical scientists with an in vitro assessment
      technique that will more reliably determine the fragmentation of the API in
      finished tablets and the behavior of the particles when compacted. 

PMID- 25996633
TI  - Gold(I)/(III)-Catalyzed Synthesis of Cyclic Ethers; Valency-Controlled
      Cyclization Modes.
AB  - Strategic use of oxophilic (hard) gold(III) and pi-philic (soft) gold(I)
      catalysts provides access to two types of cyclic ethers from propargylic
      alcohols. Thus, heating propargylic alcohols with an oxophilic gold(III) catalyst
      (AuBr3) results in cyclization to afford cyclic ethers bearing an acetylenic
      moiety, due to coordination of gold(III) to the oxygen of the propargylic
      hydroxyl group. On the other hand, propargylic alcohols with a pi-philic gold(I)
      catalyst (Ph3PAuNTf2) induces Meyer-Schuster rearrangement to afford alpha,beta
      unsaturated ketones, which undergo gold(III)-catalyzed intramolecular oxa-Michael
      addition to afford cyclic ethers bearing a carbonyl group, due to coordination of
      gold(III) to the oxygen of the carbonyl group. 

PMID- 25996634
TI  - Pediatric Deceased Donation-A Report of the Transplantation Society Meeting in
      Geneva.
AB  - The Ethics Committee of The Transplantation Society convened a meeting on
      pediatric deceased donation of organs in Geneva, Switzerland, on March 21 to 22,
      2014. Thirty-four participants from Africa, Asia, the Middle East, Oceania,
      Europe, and North and South America explored the practical and ethical issues
      pertaining to pediatric deceased donation and developed recommendations for
      policy and practice. Their expertise was inclusive of pediatric intensive care,
      internal medicine, and surgery, nursing, ethics, organ donation and procurement,
      psychology, law, and sociology. The report of the meeting advocates the routine
      provision of opportunities for deceased donation by pediatric patients and
      conveys an international call for the development of evidence-based resources
      needed to inform provision of best practice care in deceased donation for
      neonates and children. 

PMID- 25996635
TI  - Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS) for
      noninvasive early cancer detection and tissue hypoxia monitoring.
AB  - This study introduces a novel noninvasive differential photoacoustic method,
      Wavelength Modulated Differential Photoacoustic Spectroscopy (WM-DPAS), for
      noninvasive early cancer detection and continuous hypoxia monitoring through
      ultrasensitive measurements of hemoglobin oxygenation levels (StO2 ). Unlike
      conventional photoacoustic spectroscopy, WM-DPAS measures simultaneously two
      signals induced from square-wave modulated laser beams at two different
      wavelengths where the absorption difference between maximum deoxy- and oxy
      hemoglobin is 680 nm, and minimum (zero) 808 nm (the isosbestic point). The two
      wavelength measurement efficiently suppresses background, greatly enhances the
      signal to noise ratio and thus enables WM-DPAS to detect very small changes in
      total hemoglobin concentration (CHb ) and oxygenation levels, thereby identifying
      pre-malignant tumors before they are anatomically apparent. The non-invasive
      nature also makes WM-DPAS the best candidate for ICU bedside hypoxia monitoring
      in stroke patients. Sensitivity tunability is another special feature of the
      technology: WM-DPAS can be tuned for different applications such as quick cancer
      screening and accurate StO2 quantification by selecting a pair of parameters,
      signal amplitude ratio and phase shift. The WM-DPAS theory has been validated
      with sheep blood phantom measurements. Sensitivity comparison between
      conventional single-ended signal and differential signal. 

PMID- 25996636
TI  - Membrane-derived phospholipids control synaptic neurotransmission and plasticity.
AB  - Synaptic communication is a dynamic process that is key to the regulation of
      neuronal excitability and information processing in the brain. To date, however,
      the molecular signals controlling synaptic dynamics have been poorly understood.
      Membrane-derived bioactive phospholipids are potential candidates to control
      short-term tuning of synaptic signaling, a plastic event essential for
      information processing at both the cellular and neuronal network levels in the
      brain. Here, we showed that phospholipids affect excitatory and inhibitory
      neurotransmission by different degrees, loci, and mechanisms of action. Signaling
      triggered by lysophosphatidic acid (LPA) evoked rapid and reversible depression
      of excitatory and inhibitory postsynaptic currents. At excitatory synapses, LPA
      induced depression depended on LPA1/Galphai/o-protein/phospholipase C/myosin
      light chain kinase cascade at the presynaptic site. LPA increased myosin light
      chain phosphorylation, which is known to trigger actomyosin contraction, and
      reduced the number of synaptic vesicles docked to active zones in excitatory
      boutons. At inhibitory synapses, postsynaptic LPA signaling led to
      dephosphorylation, and internalization of the GABAAgamma2 subunit through the
      LPA1/Galpha12/13-protein/RhoA/Rho kinase/calcineurin pathway. However, LPA
      induced depression of GABAergic transmission was correlated with an endocytosis
      independent reduction of GABAA receptors, possibly by GABAAgamma2
      dephosphorylation and subsequent increased lateral diffusion. Furthermore,
      endogenous LPA signaling, mainly via LPA1, mediated activity-dependent inhibitory
      depression in a model of experimental synaptic plasticity. Finally, LPA
      signaling, most likely restraining the excitatory drive incoming to motoneurons,
      regulated performance of motor output commands, a basic brain processing task. We
      propose that lysophospholipids serve as potential local messengers that tune
      synaptic strength to precedent activity of the neuron. 

PMID- 25996637
TI  - Case Study: Diffuse Large B-Cell Lymphoma Arising in Ovarian Mature Cystic
      Teratoma.
AB  - We describe an unexpected finding of diffuse large B-cell lymphoma associated
      with mature cystic teratoma of the ovary. A 68-yr-old woman with a complex left
      ovarian cystic mass on imaging underwent bilateral salpingo-oophorectomy,
      lymphadenectomy, appendicectomy, and omentectomy. Histopathologic examination
      revealed nodules of malignant non-Hodgkin lymphoma within the teratoma. A
      diagnosis of diffuse large B-cell lymphoma, germinal center cell subtype by Hans
      criteria was made after immunostaining and molecular studies. The patient was
      treated with R-CHOP chemotherapy and remains disease-free at 14-mo follow-up. 

PMID- 25996638
TI  - Economic evidence on identifying clinically actionable findings with whole-genome
      sequencing: a scoping review.
AB  - The American College of Medical Genetics and Genomics (ACMG) recommends that
      mutations in 56 genes for 24 conditions are clinically actionable and should be
      reported as secondary findings after whole-genome sequencing (WGS). Our aim was
      to identify published economic evaluations of detecting mutations in these genes
      among the general population or among targeted/high-risk populations and
      conditions and identify gaps in knowledge. A targeted PubMed search from 1994
      through November 2014 was performed, and we included original, English-language
      articles reporting cost-effectiveness or a cost-to-utility ratio or net
      benefits/benefit-cost focused on screening (not treatment) for conditions and
      genes listed by the ACMG. Articles were screened, classified as targeting a high
      risk or general population, and abstracted by two reviewers. General population
      studies were evaluated for actual cost-effectiveness measures (e.g., incremental
      cost-effectiveness ratios (ICER)), whereas studies of targeted populations were
      evaluated for whether at least one scenario proposed was cost-effective (e.g.,
      ICER of <=$100,000 per life-year or quality-adjusted life-year gained). A total
      of 607 studies were identified, and 32 relevant studies were included. Identified
      studies addressed fewer than one-third (7 of 24; 29%) of the ACMG conditions. The
      cost-effectiveness of screening in the general population was examined for only 2
      of 24 conditions (8%). The cost-effectiveness of most genetic findings that the
      ACMG recommends for return has not been evaluated in economic studies or in the
      context of screening in the general population. The individual studies do not
      directly address the cost-effectiveness of WGS.

PMID- 25996641
TI  - Phloretin inhibits interleukin-1beta-induced COX-2 and ICAM-1 expression through
      inhibition of MAPK, Akt, and NF-kappaB signaling in human lung epithelial cells.
AB  - Phloretin, a flavonoid isolated from the apple tree, is reported to have anti
      inflammatory, anti-oxidant, and anti-adiposity effects. In this study, we
      evaluated the suppressive effects of phloretin on intercellular adhesion molecule
      1 (ICAM-1) and cyclooxygenase (COX)-2 expression in IL-1beta-stimulated human
      lung epithelial A549 cells. The cells were pretreated with various concentrations
      of phloretin (3-100 MUM), followed by induced inflammation by IL-1beta. Phloretin
      inhibited levels of prostaglandin E2, decreased COX-2 expression, and suppressed
      IL-8, monocyte chemotactic protein 1, and IL-6 production. It also decreased ICAM
      1 gene and protein expression and suppressed monocyte adhesion to inflammatory
      A549 cells. Phloretin also significantly inhibited Akt and mitogen-activated
      protein kinase (MAPK) phosphorylation and decreased nuclear transcription factor
      kappa-B (NF-kappaB) subunit p65 protein translocation into the nucleus. In
      addition, ICAM-1 and COX-2 expression was suppressed by pretreatment with both
      MAPK inhibitors and phloretin in inflammatory A549 cells. However, phlorizin, a
      derivative of phloretin, did not suppress the inflammatory response in IL-1beta
      stimulated A549 cells. These results suggest that phloretin might have an anti
      inflammatory effect by inhibiting proinflammatory cytokine, COX-2, and ICAM-1
      expression via blocked NF-kappaB and MAPK signaling pathways.

PMID- 25996639
TI  - Exome sequencing identifies rare variants in multiple genes in atrioventricular
      septal defect.
AB  - PURPOSE: The genetic etiology of atrioventricular septal defect (AVSD) is unknown
      in 40% cases. Conventional sequencing and arrays have identified the etiology in
      only a minority of nonsyndromic individuals with AVSD. METHODS: Whole-exome
      sequencing was performed in 81 unrelated probands with AVSD to identify
      potentially causal variants in a comprehensive set of 112 genes with strong
      biological relevance to AVSD. RESULTS: A significant enrichment of rare and rare
      damaging variants was identified in the gene set, compared with controls (odds
      ratio (OR): 1.52; 95% confidence interval (CI): 1.35-1.71; P = 4.8 * 10(-11)).
      The enrichment was specific to AVSD probands, compared with a cohort without AVSD
      with tetralogy of Fallot (OR: 2.25; 95% CI: 1.84-2.76; P = 2.2 * 10(-16)). Six
      genes (NIPBL, CHD7, CEP152, BMPR1a, ZFPM2, and MDM4) were enriched for rare
      variants in AVSD compared with controls, including three syndrome-associated
      genes (NIPBL, CHD7, and CEP152). The findings were confirmed in a replication
      cohort of 81 AVSD probands. CONCLUSION: Mutations in genes with strong biological
      relevance to AVSD, including syndrome-associated genes, can contribute to AVSD,
      even in those with isolated heart disease. The identification of a gene set
      associated with AVSD will facilitate targeted genetic screening in this cohort.

PMID- 25996642
TI  - Postoperative Complications in Patients With Unrecognized Obesity Hypoventilation
      Syndrome Undergoing Elective Noncardiac Surgery.
AB  - BACKGROUND: Among patients with OSA, a higher number of medical morbidities are
      known to be associated with those who have obesity hypoventilation syndrome (OHS)
      compared with OSA alone. OHS can pose a higher risk of postoperative
      complications after elective noncardiac surgery (NCS) and often is unrecognized
      at the time of surgery. The objective of this study was to retrospectively
      identify patients with OHS and compare their postoperative outcomes with those of
      patients with OSA alone. METHODS: Patients meeting criteria for OHS were
      identified within a large cohort with OSA who underwent elective NCS at a major
      tertiary care center. We identified postoperative outcomes associated with OSA
      and OHS as well as the clinical determinants of OHS (BMI, apnea-hypopnea index
      [AHI]). Multivariable logistic and linear regression models were used for
      dichotomous and continuous outcomes, respectively. RESULTS: Patients with
      hypercapnia from definite or possible OHS and overlap syndrome are more likely to
      experience postoperative respiratory failure (OR, 10.9; 95% CI, 3.7-32.3; P <
      .0001), postoperative heart failure (OR, 5.4; 95% CI, 1.9-15.7; P = .002),
      prolonged intubation (OR, 3.1; 95% CI, 0.6-15.3; P = .2), postoperative ICU
      transfer (OR, 10.9; 95% CI, 3.7-32.3; P < .0001), and longer ICU (?-coefficient,
      0.86; SE, 0.32; P = .009) and hospital (?-coefficient, 2.94; SE, 0.87; P = .0008)
      lengths of stay compared with patients with OSA. Among the clinical determinants
      of OHS, neither BMI nor AHI showed associations with any postoperative outcomes
      in univariable or multivariable regression. CONCLUSIONS: Better emphasis is
      needed on preoperative recognition of hypercapnia among patients with OSA or
      overlap syndrome undergoing elective NCS.

PMID- 25996643
TI  - Synthesis and Characterization of Organo-Rare-Earth Metal Monoalkyl Complexes
      Supported by Carbon sigma-Bonded Indolyl Ligands: High Specific Isoprene 1,4-Cis
      Polymerization Catalysts.
AB  - A series of N-protected 3-imino-functionalized indolyl ligands 1-R-3
      (R'N?CH)C8H5N [R = Bn, R' = 2,6-(i)Pr2C6H3 (HL(1)); R = CH3, R' = 2,6-(i)Pr2C6H3
      (HL(2)); R = Bn, R' = (t)Bu (HL(3))] and 1-CH3-2-(2,6-(i)Pr2C6H3N?CH)C8H5N
      (HL(4)) was prepared via reactions of N-protected indolyl aldehydes with
      corresponding amines. The C-H sigma-bond metathesis followed by alkane
      elimination reactions between RE(CH2SiMe3)3(thf)2 and HL(1)-HL(3) afforded the
      carbon sigma-bonded indolyl-ligated rare-earth metal monoalkyl complexes.
      Reactions of RE(CH2SiMe3)3(thf)2 with 2 equiv of HL(1) or HL(2) gave the carbon
      sigma-bonded indolyl-ligated rare-earth metal monoalkyl complexes L(1)2RECH2SiMe3
      (RE = Y(1), Er(2), Dy(3)) and L(2)2RECH2SiMe3 (RE = Y(5), Er(6), Dy(7), Yb(8)),
      while reaction of Yb(CH2SiMe3)3(thf)2 with 2 equiv of HL(1) afforded the
      ytterbium dialkyl complex L(1)Yb(CH2SiMe3)2(thf)2 (4). Reactions of
      RE(CH2SiMe3)3(thf)2 with HL(3) gave the tris(heteroaryl) rare-earth metal
      complexes L(3)3RE (RE = Y(9), Er(10)). In the presence of cocatalysts, the rare
      earth metal monoalkyl complexes initiated isoprene polymerization with a high
      activity (90% conversion of 1000 equiv of isoprene in 25 min) producing polymers
      with high regio- and stereoselectivity (1,4-cis polymers up to 99%). 

PMID- 25996644
TI  - The fate of pediatric prescriptions in community pharmacies.
AB  - OBJECTIVES: The purpose of this study was to describe behaviors of community
      pharmacists related to pediatric prescriptions and examine the effect of
      demographic and situational factors on behaviors and confidence in performing
      recommended activities when dispensing medications for pediatric patients.
      METHODS: The study employed a self-administered survey of community pharmacists
      in a regional chain. One intervention group attended a live continuing education
      session. A second intervention group received a dosing guide in the mail. One
      month after the intervention, both intervention groups and a control group
      completed the survey. RESULTS: Sixty pharmacists participated, for a response
      rate of 61%. Obtaining a weight for a pediatric prescription was reported as
      difficult by participants, and 60% rarely obtained a weight if one was not
      provided. Only 32% of participants reported calculating a dose when the weight
      was available. The majority (92%) of participants stated they were confident in
      calculating a dose and detecting a dosing error for a child. Only the
      pharmacist's perception of the organizational culture correlated with their
      behaviors and level of confidence toward performing the activities surveyed (P <
      0.005). Because of the small number of participants in the continuing education
      program, the impact of the intervention was unable to be measured. CONCLUSIONS:
      Pharmacists rarely check the accuracy of a weight-based dose for pediatric
      prescriptions, although they are confident in their ability to do so. Integrating
      this activity into the pharmacist's workflow and pharmacy culture is critical to
      reducing pediatric medication errors and promoting patient safety.

PMID- 25996645
TI  - Shifting material source of Chinese Loess since ~2.7 Ma reflected by Sr isotopic
      composition.
AB  - Deciphering the sources of eolian dust on the Chinese Loess Plateau (CLP) is
      fundamental to reconstruct paleo-wind patterns and paleo-environmental changes.
      Existing datasets show contradictory source evolutions of eolian dust on the CLP,
      both on orbital and tectonic timescales. Here, the silicate Sr and Nd isotopic
      compositions of a restricted grain size fraction (28-45 MUm) were measured to
      trace the source evolution of the CLP since ~2.7 Ma. Our results revealed an
      unchanged source on orbital timescales but a gradual source shift from the Qilian
      Mountains to the Gobi Altay Mountains during the past 2.7 Ma. Both tectonic
      uplift and climate change may have played important roles for this shift. The
      later uplift of the Gobi Altay Mountains relative to the Qilian Mountains since 5
      +/- 3 Ma might be responsible for the increasing contribution of Gobi materials
      to the source deserts in Alxa arid lands. Enhanced winter monsoon may also
      facilitate transportation of Gobi materials from the Alxa arid lands to the CLP.
      The shifting source of Asian dust was also reflected in north Pacific sediments.
      The finding of this shifting source calls for caution when interpreting the long
      term climate changes based on the source-sensitive proxies of the eolian
      deposits.

PMID- 25996646
TI  - New Insights into Improving Rate Performance of Lithium-Rich Cathode Material.
AB  - A Sn doping strategy is demonstrated to improve lithium diffusion kinetics by
      expanding the spacing of (003) planes without destroying the layered structure. A
      large (003) spacing will significantly decrease the energy barrier associated
      with lithium diffusion. Besides better rate capability, the Sn-doped material
      exhibits an unexpected much improved capacity above 3.0 V (vs Li(+) /Li), which
      is highly desired in future applications. 

PMID- 25996647
TI  - Fenugreek seed extract attenuates cisplatin-induced testicular damage in Wistar
      rats.
AB  - Cisplatin (CIS) provides oxidative stress and inflammations in testicular
      tissues. Fenugreek seed extract (FSE) is a widely used herbal medicine with
      potent antioxidant and anti-inflammation properties. The purpose of this study
      was to investigate the protective effects and the possible mechanisms of FSE
      against CIS-induced testicular damage in rats. Adult male Wistar rats were given
      vehicle, single dose of CIS alone (10 mg kg(-1)), single dose of FSE alone or
      single dose of CIS followed by FSE (50, 100 or 200 mg kg(-1)) every day for 5
      days. On day 6, oxidative stress and apoptotic testicular toxicity were
      evaluated. FSE attenuated both germ cell degenerations and apoptosis in
      seminiferous tubules in CIS-treated rats. Furthermore, FSE counteracted CIS
      induced oxidative stress in rats as assessed by the restoration of superoxide
      dismutase and catalase activities and reduction in the myeloperoxidase activity
      and malondialdehyde levels in testes. CIS increased expressions of inducible
      nitric oxide synthase and nuclear factor-kappa B in testicular tissues.
      Importantly, treatment with FSE at all doses effectively alleviated all of these
      inflammatory parameters in testes. Based on these results, we concluded that FSE
      reduces CIS-induced reproductive toxicity in rats by the suppression of
      testicular oxidative stress, apoptosis and inflammations.

PMID- 25996648
TI  - Heck-Suzuki Tandem Reaction for the Synthesis of 3-Benzazepines.
AB  - A novel procedure for the Heck-Suzuki tandem reaction suitable for the
      construction of nitrogen-containing medium rings was developed to provide access
      toward the 3-benzazepine framework. 

PMID- 25996649
TI  - Evaluation of PPARalpha activation by known blueberry constituents.
AB  - BACKGROUND: Anthocyanins are known to have hypolipidemic properties. It was
      deemed necessary to determine whether major blueberry anthocyanins and catechins
      are ligands for the transcription factor peroxisome proliferator activated
      receptor alpha isoform (PPARalpha), and compare activation with known PPARalpha
      agonistic constituents, pterostilbene and resveratrol. It was also considered
      important to investigate the effect of pterostilbene on PPARalpha gene
      expression, and relate results with hepatic mRNA PPARalpha expression up
      regulation observed previously in hamsters fed a diet supplemented with blueberry
      peels extract (BBX). RESULTS: The anthocyanins and catechins did not activate
      PPARalpha. Only pterostilbene exhibited a dose-dependent activation of PPARalpha
      in H4IIEC3 cells. The resveratrol responses were lower than those of
      pterostilbene. Pterostilbene significantly and dose-dependently (at 10, 20 and 50
      umol L(-1) ) increased PPARalpha gene expression and the effect at 10 umol L(-1)
      was greater than 100 and 200 umol L(-1) of fenofibrate. Analysis of BBX showed
      levels of pterostilbene and resveratrol at 418 and 2381 ng g(-1), respectively.
      CONCLUSION: Anthocyanins and catechins do not appear to contribute to the up
      regulation of hepatic PPARalpha expression observed in hamsters. While
      pterostilbene and resveratrol demonstrated PPARalpha activation, their levels in
      BBX do not seem to be at efficacious concentrations. These stilbenes may
      contribute to the up-regulation of PPARalpha expression by acting synergistically
      with each other or with other constituents in BBX.

PMID- 25996651
TI  - Changing 14-year trends in the epidemiology of hepatitis B virus infection in
      rural and urban Central-Eastern European areas.
AB  - In Poland, the prevalence of HBV infection constitutes an emerging public health
      concern. The aim of the study was to analyse changes in hepatitis B incidence
      rate by age, gender and place of residence in Poland between 1999 and 2012. The
      data were obtained from Polish state statistics institutions such as the National
      Institute of Public Health and State Sanitary Inspection. Relationships of
      hepatitis B incidence with age, gender and rural/urban areas were investigated
      using chi(2) and tests for two proportions with Bonferroni adjustment. The
      incidence of hepatitis B in rural and urban populations was compared using
      Wilcoxon's signed-rank tests. Joinpoint regression was used to analyse trends in
      hepatitis B incidence rate. In Poland, a total of 26 660 cases of hepatitis B
      were reported in the studied period and 31.6% of these cases occurred in rural
      areas. There was significantly declining tendency in the hepatitis B incidence
      rate in the initial period of the study. However, there were periods of
      significant increase of HBV incidence rate in women from rural areas aged 15-24
      years (9.4%/year) and in women from urban areas aged 15-24 years (10.9%/year) and
      25-64 years (3.8%/year) in the final years of the observation. Despite the
      success in controlling this infection, a significant increase in the incidence of
      hepatitis B among young women living in rural and urban areas, as well as in
      adult women in urban areas, has been noted. 

PMID- 25996650
TI  - Peripheral Microvascular Vasodilatory Response to Estradiol and Genistein in
      Women with Insulin Resistance.
AB  - OBJECTIVE: E2 enhances vasodilation in healthy women, but vascular effects of the
      phytoestrogen GEN are still under investigation. IR compromises microvascular
      function. We therefore examined the interaction of E2 , GEN, and IR on
      microvascular vasodilatory responsiveness. METHODS: We hypothesized that E2 and
      GEN increase microvascular vasodilation in healthy women (control, n = 8, 23 +/-
      2 year, BMI: 25.9 +/- 2.9 kg/m2) but not in women with IR (n = 7, 20 +/- 1 year,
      BMI: 27.3 +/- 3.0 kg/m2). We used the cutaneous circulation as a model of
      microvascular vasodilatory function. We determined CVC with laser Doppler
      flowmetry and beat-to-beat blood pressure during local cutaneous heating (42 
      degrees C) with E2 or GEN microdialysis perfusions. Because heat-induced
      vasodilation is primarily an NO-mediated response, we examined microvascular
      vasodilation with and without L-NMMA. RESULTS: In C, E2 enhanced CVC (94.4 +/-
      2.6% vs. saline 81.6 +/- 4.2% CVCmax , p < 0.05), which was reversed with L-NMMA
      (80.9 +/- 7.8% CVCmax , p < 0.05), but GEN did not affect vasodilation. Neither
      E2 nor GEN altered CVC in IR, although L-NMMA attenuated CVC during GEN.
      CONCLUSIONS: Our study does not support improved microvascular responsiveness
      during GEN exposure in healthy young women, and demonstrates that neither E2 nor
      GEN improves microvascular vasodilatory responsiveness in women with IR.

PMID- 25996652
TI  - Adaptation of Extremophilic Proteins with Temperature and Pressure: Evidence from
      Initiation Factor 6.
AB  - In this work, we study dynamical properties of an extremophilic protein,
      Initiation Factor 6 (IF6), produced by the archeabacterium Methanocaldococcus
      jannascii, which thrives close to deep-sea hydrothermal vents where temperatures
      reach 80  degrees C and the pressure is up to 750 bar. Molecular dynamics
      simulations (MD) and quasi-elastic neutron scattering (QENS) measurements give
      new insights into the dynamical properties of this protein with respect to its
      eukaryotic and mesophilic homologue. Results obtained by MD are supported by QENS
      data and are interpreted within the framework of a fractional Brownian dynamics
      model for the characterization of protein relaxation dynamics. IF6 from M.
      jannaschii at high temperature and pressure shares similar flexibility with its
      eukaryotic homologue from S. cerevisieae under ambient conditions. This work
      shows for the first time, to our knowledge, that the very common pattern of
      corresponding states for thermophilic protein adaptation can be extended to
      thermo-barophilic proteins. A detailed analysis of dynamic properties and of
      local structural fluctuations reveals a complex pattern for "corresponding"
      structural flexibilities. In particular, in the case of IF6, the latter seems to
      be strongly related to the entropic contribution given by an additional, C
      terminal, 20 amino-acid tail which is evolutionary conserved in all mesophilic
      IF6s. 

PMID- 25996653
TI  - Chloroplast phylogeny of Triticum/Aegilops species is not incongruent with an
      ancient homoploid hybrid origin of the ancestor of the bread wheat D-genome.

PMID- 25996654
TI  - Atypical IgM multiple myeloma with deletion of c-MAF.
AB  - IgM multiple myeloma (MM) is a rare subtype of myeloma that shares clinical and
      pathological features with Waldenstrom's macroglobulinaemia. These are two
      separate entities that differ both in therapy and prognosis. We report a 57-year
      old male, who presented with anaemia, hypercalcaemia, acute renal failure and
      several vertebral fractures that clinically suggested a multiple myeloma. Further
      investigations revealed a serum monoclonal component of IgM lambda type and a
      bone marrow infiltrated by small, lymphoplasmocytic cells. IgM MM was finally
      diagnosed by means of both inmunophenotypic and immunohistochemistry techniques,
      stressing the importance of inmunophenotypic evaluation when clinical and
      morphological features are discordant. Fluorescence in situ hybridization (FISH)
      studies disclosed a particular combination of deletion 13q14, t(11;14) and
      monoallelic deletion C-MAF without t(14;16). The clinical evolution after a
      Bortezomib-containing polychemotherapy and autologous stem cell transplantation
      (ASCT) conditioned with busulphan and melphalan is also presented. This very
      uncommon case highlights the impact of immunophenotyping on the differential
      diagnosis between IgM MM and WM, to choose the best treatment and establish an
      appropriate outcome.

PMID- 25996655
TI  - Anticarcinogenic Effects of Dietary Phytoestrogens and Their Chemopreventive
      Mechanisms.
AB  - Phytoestrogens are phenolic compounds derived from plants and exert an estrogenic
      as well as an antiestrogenic effect and also various biological efficacies.
      Chemopreventive properties of phytoestrogens has emerged from epidemiological
      observations indicating that the incidence of some cancers including breast and
      prostate cancers is much lower in Asian people, who consume significantly higher
      amounts of phytoestrogens than Western people. There are 4 main classes of
      phytoestrogens: isoflavones, stilbenes, coumestans, and lignans. Currently,
      resveratrol is recognized as another major phytoestrogen present in grape and red
      wine and has been studied in many biological studies. Phytoestrogens have
      biologically diverse profitabilities and advantages such as low cytotoxicity to
      patients, lack of side effects in clinical trials, and pronounced benefits in a
      combined therapy. In this review, we highlighted the effects of genistein,
      daidzein, and resveratrol in relation with their anticarcinogenic activity. A lot
      of in vitro and in vivo results on their chemopreventive properties were
      presented along with the underlying mechanisms. Besides well-known mechanisms
      such as antioxidant property and apoptosis, newly elucidated anticarcinogenic
      modes of action including epigenetic modifications and topoisomerase inhibition
      have been provided to examine the possibility of phytoestrogens as promising
      reagents for cancer chemoprevention and/or treatment and to suggest the
      importance of plant-based diet of phytoestrogens. 

PMID- 25996656
TI  - Macroautophagy is essential for killing of intracellular Burkholderia
      pseudomallei in human neutrophils.
AB  - Neutrophils play a key role in the control of Burkholderia pseudomallei, the
      pathogen that causes melioidosis. Here, we show that survival of intracellular B.
      pseudomallei was significantly increased in the presence of 3-methyladenine or
      lysosomal cathepsin inhibitors. The LC3-flux was increased in B. pseudomallei
      infected neutrophils. Concordant with this result, confocal microscopy analyses
      using anti-LC3 antibodies revealed that B. pseudomallei-containing phagosomes
      partially overlapped with LC3-positive signal at 3 and 6 h postinfection.
      Electron microscopic analyses of B. pseudomallei-infected neutrophils at 3 h
      revealed B. pseudomallei-containing phagosomes that occasionally fused with
      phagophores or autophagosomes. Following infection with a B. pseudomallei mutant
      lacking the Burkholderia secretion apparatus Bsa Type III secretion system,
      neither this characteristic structure nor bacterial escape into the cytosol were
      observed. These findings indicate that human neutrophils are able to recruit
      autophagic machinery adjacent to B. pseudomallei-containing phagosomes in a Type
      III secretion system-dependent manner.

PMID- 25996659
TI  - Early death in active professional athletes: Trends and causes.
AB  - The objective of the study was to examine mortality trends and causes of death
      among professional athletes from the four major sports in North America who died
      during their playing careers. 205 deceased athletes who were registered as active
      when they died from the National Basketball Association (NBA), National Football
      League (NFL), National Hockey League (NHL), and Major League Baseball (MLB) were
      examined. Results were compared with the Canadian and U.S. general population.
      The leading causes of death in players reflected the leading causes of death in
      the Canadian and U.S. general population (i.e., car accidents). Descriptively,
      NFL and NBA players had a higher likelihood of dying in a car accident (OR 1.75,
      95% CI: 0.91-3.36) compared with NHL and MLB players. In addition, NFL and NBA
      players had a significantly higher likelihood of dying from a cardiac-related
      illness (OR 4.44, 95% CI: 1.59-12.43). Mortality trends were disproportionate to
      team size. Overall, death in active athletes is low. Out of 53 400 athletes who
      have historically played in the four leagues, only 205 died while active (0.38%).
      Future examinations into the trends and causes of mortality in elite athlete
      populations will create a better understanding of health-related risks in elite
      sport. 

PMID- 25996657
TI  - Chromatin-bound bacterial effector ankyrin A recruits histone deacetylase 1 and
      modifies host gene expression.
AB  - Control of host epigenetics is becoming evident as a mechanism by which symbionts
      and pathogens survive. Anaplasma phagocytophilum, an obligate intracellular
      bacterium, down-regulates multiple host defence genes where histone deacetylase 1
      (HDAC1) binds and histone 3 is deacetylated at their promoters, including the
      NADPH oxidase component, CYBB. How HDAC1 is targeted to defence gene promoters is
      unknown. Ankyrin A (AnkA), an A. phagocytophilum type IV secretion system
      effector, enters the granulocyte nucleus, binds stretches of AT-rich DNA and
      alters transcription of antimicrobial defence genes, including down-regulation of
      CYBB. Here we found AnkA binds to a predicted matrix attachment region in the
      proximal CYBB promoter. Using the CYBB promoter as a model of cis-gene silencing,
      we interrogated the mechanism of AnkA-mediated CYBB repression. The N-terminus of
      AnkA was critical for nuclear localization, the central ANK repeats and C
      terminus were important for DNA binding, and most promoter activity localized to
      the central ANK repeats. Furthermore, a direct interaction between AnkA and HDAC1
      was detected at the CYBB promoter, and was critical for AnkA-mediated CYBB
      repression. This novel microbial manipulation of host chromatin and gene
      expression provides important evidence of the direct effects that prokaryotic
      nuclear effectors can exert over host transcription and function. 

PMID- 25996661
TI  - Incidence, severity and prognosis associated with hypernatremia in dogs and cats.
AB  - BACKGROUND: Hypernatremia has been associated with substantial morbidity and
      death in human patients. The incidence and importance of hypernatremia in dogs
      and cats has not been determined. HYPOTHESIS/OBJECTIVES: To describe the
      incidence of and prognosis associated with hypernatremia in dogs and cats at a
      university teaching hospital. ANIMALS: A total of 16,691 dogs and 4,211 cats with
      measured blood or serum sodium concentration. METHODS: Retrospective study.
      Medical records of animals with a blood or serum sodium concentration measured
      during a 60-month period were reviewed to determine the severity of hypernatremia
      and its associated case fatality rate. Cases with moderate (11-15 mmol/L above
      the reference range) or severe hypernatremia (>=16 mmol/L above the reference
      range) were further reviewed. RESULTS: A total of 957 dogs (5.7%) and 338 cats
      (8.0%) were diagnosed with hypernatremia. Case fatality rates of dogs and cats
      with hypernatremia was 20.6 and 28.1%, respectively compared to 4.4 and 4.5% with
      a normal blood or serum sodium concentration (P < .0001). The magnitude of
      hypernatremia was linearly associated with a higher case fatality rate (P <
      .0001). Hypernatremia was associated with a higher case fatality rate than
      hyponatremia. Among the animals with moderate or severe hypernatremia, 50% of
      dogs and 38.5% of cats presented with community-acquired hypernatremia, and 50%
      of dogs and 61.5% of cats developed hospital-acquired hypernatremia. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Hypernatremia was found infrequently in this population
      but was associated with increased case fatality rates in dogs and cats. Presence
      and severity of hypernatremia might be useful as a prognostic indicator.

PMID- 25996660
TI  - Exercise induced pulmonary hemorrhage in horses: American College of Veterinary
      Internal Medicine consensus statement.
AB  - BACKGROUND: Published studies of exercise-induced pulmonary hemorrhage (EIPH),
      when assessed individually, often provide equivocal or conflicting results.
      Systematic reviews aggregate evidence from individual studies to provide a global
      assessment of the quality of evidence and to inform recommendations. OBJECTIVES:
      Evaluate evidence to determine: if EIPH adversely affects the health, welfare or
      both of horses; if EIPH affects the athletic capacity of horses; the efficacy of
      prophylactic interventions for EIPH; and if furosemide affects the athletic
      capacity of horses. ANIMALS: None. MATERIALS AND METHODS: Systematic review. A
      panel of 7 experts was formed to assess evidence in the peer reviewed literature
      addressing each of the 4 objectives. Methodology followed that of the Grading of
      Recommendations, Assessment, Development, and Evaluation (GRADE). Publications
      were assessed for quality of evidence by working groups of the panel, and a
      summary of findings was presented in tables. Recommendations were based on
      quality of evidence and were determined by a vote of the panel. RESULTS: Much of
      the evidence was of low to very low quality. Experimental studies frequently
      lacked adequate statistical power. There was moderate to high quality evidence
      that EIPH is progressive, is associated with lung lesions, that it adversely
      affects racing performance, that severe EIPH (Grade 4) is associated with a
      shorter career duration, that furosemide is efficacious in decreasing the
      incidence and severity of EIPH, and that administration of furosemide is
      associated with superior race performance. CONCLUSIONS AND CLINICAL SIGNIFICANCE:
      Strong recommendation that EIPH be considered a disease and a weak recommendation
      for use of furosemide in management of racehorses with EIPH.

PMID- 25996662
TI  - Dorsal compressive atlantoaxial bands and the craniocervical junction syndrome:
      association with clinical signs and syringomyelia in mature cavalier King Charles
      spaniels.
AB  - BACKGROUND: Dorsal compressive lesions at the atlantoaxial junction (ie, AA
      bands) occur in dogs with Chiari-like malformations (CMs), but their clinical
      relevance is unclear. OBJECTIVE: Investigate the influence of AA bands on
      clinical status and syringomyelia (SM) in mature cavalier King Charles spaniels
      (CKCS). ANIMALS: Thirty-six CKCS, 5-12 years of age, including 20 dogs with
      neuropathic pain. METHODS: Dogs were examined and assigned a neurologic grade.
      Magnetic resonance imaging (MRI) of the craniocervical junction was performed
      with the craniocervical junction extended and flexed (ie, normal standing
      position). Imaging studies were assessed for the presence of an AA band, CM, SM
      or some combination of these findings. Band and SM severity were quantified using
      an objective compression index and ordinal grading scale, respectively. RESULTS:
      Of 36 CKCS imaged, 34 had CM. Atlantoaxial bands were present in 31 dogs and were
      more prominent in extended than flexed positions. Syringomyelia was found in 26
      dogs, 23 of which also had AA bands. Bands were associated with both the presence
      (P = .0031) and severity (P = .008) of clinical signs and SM (P = .0147, P =
      .0311, respectively). Higher compression indices were associated with more severe
      SM (P = .0137). CONCLUSIONS: Prevalence of AA bands in older CKCS is high.
      Positioning of dogs in extension during MRI enhances the sensitivity of the study
      for detecting this important abnormality. There were significant associations
      among AA bands, clinical signs, and SM in dogs with CM; additional work is needed
      to understand whether or not this relationship is causal.

PMID- 25996664
TI  - Novel reversible selective inhibitor of nuclear export shows that CRM1 is a
      target in colorectal cancer cells.
AB  - Colorectal cancer arises via a multistep carcinogenic process and the
      deregulation of multiple pathways. Thus, the simultaneous targeting of multiple
      pathways may be a promising therapeutic approach for colorectal treatment. CRM1
      is an attractive cancer drug target, because it can regulate multiple pathways
      and tumor suppressor proteins. In this study, we investigated the anti-tumor
      activity of a novel reversible CRM1 inhibitor S109 in colorectal cancer. Our data
      demonstrate that S109 inhibits proliferation and induces cell cycle arrest in
      colorectal cancer cells. Mechanistically, we demonstrate that the activity of
      S109 is associated with the nuclear retention of major tumor suppress proteins.
      Furthermore, the Cys528 mutation of CRM1 prevented the ability of S109 to block
      nuclear export and inhibit the proliferation of colorectal cancer cells.
      Interestingly, S109 decreased the CRM1 protein level via proteasomal pathway. We
      argue that reversible CRM1 inhibitors but not irreversible inhibitors can induce
      the degradation of CRM1, because the dissociation of reversible inhibitors of
      CRM1 changes the conformation of CRM1. Taken together, these findings demonstrate
      that CRM1 is a valid target for the treatment of colorectal cancer and provide a
      basis for the development of S109 therapies for colorectal cancer. 

PMID- 25996665
TI  - Malignant melanoma on female clitoris with bidirectional upper and lower
      lymphatic flow.

PMID- 25996668
TI  - Living With Cancer Alone? The Experiences of Singles Diagnosed With Colorectal
      Cancer.
AB  - This paper seeks to understand the experiences of single colorectal cancer
      patients. This study consisted of 12 semi-structured interviews that were
      digitally voice-recorded, transcribed, and analyzed. Six main themes emerged: (a)
      gradual shift in view of cancer diagnosis from fatalistic to normalized, (b)
      perception of cancer as a nadir experience, (c) concerns of singlehood, (d)
      factors influencing cancer experiences, (e) factors influencing coping with
      cancer, and (f) range of responses towards cancer diagnosis. Singles with
      colorectal cancer require short- to long-term individualized care plans, and
      psycho-emotional support. This may help enhance their individual coping and
      adjustment to the diagnosis. 

PMID- 25996669
TI  - Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS.
AB  - cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and
      frequently used cytostatic drugs for the treatment of various solid tumors.
      Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS)
      method incorporating a fast and simple sample preparation protocol was developed
      for the elemental mapping of Cisplatin in the model organism Caenorhabditis
      elegans (C. elegans). The method allows imaging of the spatially-resolved
      elemental distribution of platinum in the whole organism with respect to the
      anatomic structure in L4 stage worms at a lateral resolution of 5 MUm. In
      addition, a dose- and time-dependent Cisplatin uptake was corroborated
      quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF)
      method, and the elemental mapping indicated that Cisplatin is located in the
      intestine and in the head of the worms. Better understanding of the distribution
      of Cisplatin in this well-established model organism will be instrumental in
      deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect
      of Cisplatin is based on binding the DNA by forming intra- and interstrand
      crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion
      mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans
      ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA
      damage response. With respect to survival and brood size, pme-1 deletion mutants
      were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin
      uptake was indistinguishable.

PMID- 25996670
TI  - Role of single nucleotide polymorphisms in pharmacogenomics and their association
      with human diseases.
AB  - Global statistical data shed light on an alarming trend that every year thousands
      of people die due to adverse drug reactions as each individual responds in a
      different way to the same drug. Pharmacogenomics has come up as a promising field
      in drug development and clinical medication in the past few decades. It has
      emerged as a ray of hope in preventing patients from developing potentially fatal
      complications due to adverse drug reactions. Pharmacogenomics also minimizes the
      exposure to drugs that are less/non-effective and sometimes even found toxic for
      patients. It is well reported that drugs elicit different responses in different
      individuals due to variations in the nucleotide sequences of genes encoding for
      biologically important molecules (drug-metabolizing enzymes, drug targets and
      drug transporters). Single nucleotide polymorphisms (SNPs), the most common type
      of polymorphism found in the human genome is believed to be the main reason
      behind 90% of all types of genetic variations among the individuals. Therefore,
      pharmacogenomics may be helpful in answering the question as to how inherited
      differences in a single gene have a profound effect on the mobilization and
      biological action of a drug. In the present review, we have discussed clinically
      relevant examples of SNP in associated diseases that can be utilized as markers
      for "better management of complex diseases" and attempted to correlate the drug
      response with genetic variations. Attention is also given towards the therapeutic
      consequences of inherited differences at the chromosomal level and how associated
      drug disposition and/or drug targets differ in various diseases as well as among
      the individuals.

PMID- 25996671
TI  - Gravel bars can be critical for biodiversity conservation: a case study on scaly
      sided Merganser in South china.
AB  - Gravel bars are characteristic components of river landscapes and are
      increasingly recognized as key sites for many waterbirds, though detailed studies
      on the ecological function of gravel bars for waterbirds are rare. In this study,
      we surveyed the endangered Scaly-sided Merganser Mergus squamatus along a 40 km
      river section of Yuan River, in Central China, for three consecutive winters. We
      derived the landscape metrics of river gravel bars from geo-rectified fine
      resolution (0.6 m) aerial image data. We then built habitat suitability models
      (Generalized Linear Models-GLMs) to study the effects of landscape metrics and
      human disturbance on Scaly-sided Merganser presence probability. We found that 1)
      the Scaly-sided Merganser tended to congregate at river segments with more gravel
      patches; 2) the Scaly-sided Merganser preferred areas with larger and more
      contiguous gravel patches; and 3) the number of houses along the river bank (a
      proxy for anthropogenic disturbance) had significantly negative impacts on the
      occurrence of the Scaly-sided Merganser. Our results suggest that gravel bars are
      vital to the Scaly-sided Merganser as shelters from disturbance, as well as sites
      for feeding and roosting. Therefore, maintaining the exposure of gravel bars in
      regulated rivers during the low water period in winter might be the key for the
      conservation of the endangered species. These findings have important
      implications for understanding behavioral evolution and distribution of the
      species and for delineating between habitats of different quality for
      conservation and management. 

PMID- 25996672
TI  - Eleven-year-old girl with multiple nodules on the trunk.

PMID- 25996673
TI  - Painless nodule on the external ear.

PMID- 25996674
TI  - Erythema, atrophy, and scarring on the face and arm of a young girl.

PMID- 25996675
TI  - Superficial and deep infiltrating congenital juvenile xanthogranuloma involving
      multiple skeletal muscles and associated with ulceration and generalized
      postinvolution atrophy.
AB  - We present a 2-day-old boy with a deep-seated giant juvenile xanthogranuloma
      infiltrating the skeletal muscles on his right lower limb. Unlike typical
      juvenile xanthogranuloma, the lesion has shown only partial spontaneous
      regression with large atrophic scar. However, despite the involvement multiple
      muscle on the right thigh, the patient has no evidence of orthopaedic sequelae. 

PMID- 25996677
TI  - Hypoxia pretreatment of bone marrow mesenchymal stem cells facilitates
      angiogenesis by improving the function of endothelial cells in diabetic rats with
      lower ischemia.
AB  - Endothelial dysfunction induced by unordered metabolism results in vascular
      reconstruction challenges in diabetic lower limb ischemia (DLLI). Mesenchymal
      stem cells (MSCs) are multipotent secretory cells that are suitable for clinical
      DLLI treatment, but their use has been hampered by poor survival after injection.
      Hypoxia can significantly enhance the capacity of MSCs to secrete angiogenic
      factors. We investigated transient hypoxia pretreatment of MSCs to facilitate
      revascularization in DLLI. Rat bone marrow MSCs (BM-MSCs) were cultured at
      different oxygen concentrations for varying time periods. The results indicated
      that transient pretreatment (5% O2, 48 h) not only increased the expression of
      VEGF-1alpha, ANG, HIF-1alpha and MMP-9 in BM-MSCs as assessed by real-time RT
      PCR, but also increased the expression of Bcl-2 as determined by western
      blotting. The transplantation of pretreated BM-MSCs into rats with DLLI
      demonstrated accelerated vascular reconstruction when assayed by angiography and
      immunohistochemistry. CM-Dil-labeled tracer experiments indicated that the
      survival of BM-MSCs was significantly improved, with approximately 5% of the
      injected cells remaining alive at 14 days. The expression levels of VEGF-1alpha,
      MMP-9 and VEGF-R were significantly increased, and the expression of pAKT was up
      regulated in ischemic muscle. Double immunofluorescence studies confirmed that
      the pretreated BM-MSCs promoted the proliferation and inhibited the apoptosis of
      endothelial cells. In vitro, pretreated BM-MSCs increased the migratory and tube
      forming capacity of endothelial cells (ECs). Hypoxia pretreatment of BM-MSCs
      significantly improved angiogenesis in response to tissue ischemia by
      ameliorating endothelial cell dysfunction and is a promising therapeutic
      treatment for DLLI. 

PMID- 25996678
TI  - Mesenchymal Stem Cells Derived from Peripheral Blood Retain Their Pluripotency,
      but Undergo Senescence During Long-Term Culture.
AB  - Peripheral blood-derived mesenchymal stem cells (PB-MSCs) show promise as a
      source of cells for autologous transplantation because they can be harvested
      through minimally invasive procedures. To ensure adequate numbers of cells for
      transplantation and tissue regeneration, PB-MSCs must first be cultured and
      expanded in vitro, but whether long-term passage modifies their properties has
      been poorly understood. In this study we triggered production of PB-MSCs in
      rabbits using granulocyte colony-stimulating factor (G-CSF) and AMD3100, and then
      isolated and expanded the cells in culture until they reached a state of
      senescence, usually after about 20 passages. Cultures of low-, middle-, and high
      passage numbers were compared in terms of morphology, proliferative capacity,
      phenotype, differentiation potential, apoptosis, metabolic indicators, and
      senescence. As passage number increased, MSCs retained their elongated spindle
      shape, but became larger and flatter, slowed in growth gradually, and increased
      proportion of cells showed G1 arrest. The proportions of apoptotic cells,
      production of reactive oxygen species (ROS), and ADP/ATP ratio increased with
      passage number. Expression of senescence-associated beta-galactosidase increased,
      while telomerase activity decreased. On the other hand, cultures did not show
      significant changes in phenotype or lose their ability to differentiate into
      three lineages as passage number increased. These results suggest that PB-MSCs
      maintain their stem cell properties during prolonged culturing, but they undergo
      senescence that may be due to apoptosis and production of ROS. These findings may
      help to standardize in vitro production of PB-MSCs for tissue engineering. 

PMID- 25996679
TI  - Trading Places-Switching Frataxin Function by a Single Amino Acid Substitution
      within the [Fe-S] Cluster Assembly Scaffold.

PMID- 25996680
TI  - A Comparison of Two Methods for Measuring Listening Effort As Part of an
      Audiologic Test Battery.
AB  - PURPOSE: We evaluated 2 measures of listening effort (a self-report measure and a
      word recall measure) regarding their suitability for inclusion in a comprehensive
      audiologic testing protocol. The relationship between the 2 measures was
      explored, and both measures were examined with regard to validity, sensitivity,
      and effect on speech intelligibility performance. METHOD: Thirty adults with
      normal hearing participated. Speech intelligibility performance was evaluated at
      4 signal-to-noise ratios by using keywords embedded in both high- and low-context
      sentences. Listening effort was evaluated at set intervals throughout the speech
      intelligibility task. RESULTS: Results obtained with the 2 measures were
      consistent with expected changes in listening effort. However, data obtained with
      the self-report method demonstrated greater sensitivity to these changes. The 2
      measures were uncorrelated. Under certain conditions, speech intelligibility
      performance was more negatively affected when the word recall measure was used.
      Exploration of additional theoretical and practical considerations supported a
      conclusion that the self-report measure was preferable for measuring listening
      effort simultaneously with speech intelligibility. CONCLUSION: The results of
      this study provide a rationale for preferring the self-report measure of
      listening effort over the word recall measure when testing audiologic outcomes.

PMID- 25996681
TI  - Massive Sinonasal Polyposis.

PMID- 25996682
TI  - Identification of differentially methylated markers among cytogenetic risk groups
      of acute myeloid leukemia.
AB  - Aberrant DNA methylation is known to occur in cancer, including hematological
      malignancies such as acute myeloid leukemia (AML). However, less is known about
      whether specific methylation profiles characterize specific subcategories of AML.
      We examined this issue by using comprehensive high-throughput array-based
      relative methylation analysis (CHARM) to compare methylation profiles among
      patients in different AML cytogenetic risk groups. We found distinct profiles in
      each group, with the high-risk group showing overall increased methylation
      compared with low- and mid-risk groups. The differentially methylated regions
      (DMRs) distinguishing cytogenetic risk groups of AML were enriched in the CpG
      island shores. Specific risk-group associated DMRs were located near genes
      previously known to play a role in AML or other malignancies, such as MN1, UHRF1,
      HOXB3, and HOXB4, as well as TRIM71, the function of which in cancer is not well
      characterized. These findings were verified by quantitative bisulfite
      pyrosequencing and by comparison with results available at the TCGA cancer genome
      browser. To explore the potential biological significance of the observed
      methylation changes, we correlated our findings with gene expression data
      available through the TCGA database. The results showed that decreased
      methylation at HOXB3 and HOXB4 was associated with increased gene expression of
      both HOXB genes specific to the mid-risk AML, while increased DNA methylation at
      DCC distinctive to the high-risk AML was associated with increased gene
      expression. Our results suggest that the differential impact of cytogenetic
      changes on AML prognosis may, in part, be mediated by changes in methylation. 

PMID- 25996683
TI  - Parasites and their heterophagic appetite for disease.

PMID- 25996684
TI  - Effect of Water T2 Shortening in the Quantification of in-vitro Proton MR
      Spectroscopy.
AB  - PURPOSE: This work studies the relationship between in-vitro Proton Magnetic
      Resonance Spectroscopy metabolite quantification and water T2 decay. MATERIALS
      AND METHODS: An in-vitro correspondence is established between the iron
      accumulation and the shortening of water T2 relaxation times using seven
      spherical phantoms, 6 of them were doped with an increasing concentration of iron
      metal nanoparticles solution. This is later proposed as a source of error during
      the LCModel metabolite quantification of either absolute concentrations or
      ratios. RESULTS: The Pearson's correlation coefficient between water T2 values
      against absolute metabolite concentrations was on average [r] = 0.97 and on
      average [r] = 0.85 for metabolite ratios. CONCLUSION: These results suggest that
      the shortening of T2 values should be taken into account when performing
      metabolite quantification. Also, the need of demonstrated similar results in in
      vivo studies, since the presence of iron deposits or other factors affecting the
      water T2 decay measurements could explain part of the inter-subject variability
      in the metabolite concentration and ratio quantification.

PMID- 25996685
TI  - Gelsolin Amyloidogenesis Is Effectively Modulated by Curcumin and Emetine
      Conjugated PLGA Nanoparticles.
AB  - Small molecule based therapeutic intervention of amyloids has been limited by
      their low solubility and poor pharmacokinetic characteristics. We report here,
      the use of water soluble poly lactic-co-glycolic acid (PLGA)-encapsulated
      curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively), as
      potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye
      Thioflavin T (ThT) as an indicator along with electron microscopic imaging we
      show that the presence of Cm-NPs augmented amyloid formation in gelsolin by
      skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar
      aggregates. These two types of aggregates differed in their morphologies, surface
      hydrophobicity and secondary structural signatures, confirming that they followed
      distinct pathways. In spite of differences, both these aggregates displayed
      reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control
      gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be
      reduced by either stalling or accelerating its fibrillation process. In addition,
      Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed
      gelsolin amyloids. Moreover, amyloid modulation happened at a much lower
      concentration and at a faster rate by the PLGA encapsulated compounds as compared
      to their free forms. Thus, besides improving pharmacokinetic and biocompatible
      properties of curcumin and emetine, PLGA conjugation elevates the therapeutic
      potential of both small molecules against amyloid fibrillation and toxicity. 

PMID- 25996686
TI  - Influence of sources of information about influenza vaccine on parental attitudes
      and adolescent vaccine receipt.
AB  - In 2011-2012, only 34% of 13-17 years olds in the United States (US) received
      seasonal influenza vaccine. Little is known about the link between parents'
      sources of health information, their vaccine-related attitudes, and vaccination
      of their adolescent against influenza. This study seeks to determine the
      relationship between number of sources of information on influenza vaccine,
      parental attitudes toward influenza vaccine, and influenza vaccine uptake in
      adolescents. We conducted a telephone and web-based survey among US parents of
      students enrolled in 6 middle and 5 high schools in Georgia. Bivariate and
      multivariable analyses were conducted to examine associations between the number
      of information sources about influenza vaccine and vaccine receipt and whether
      parent vaccine-related attitudes act as a mediator. The most commonly reported
      sources of information were: a physician/medical professional (95.0%), a family
      member or friend (80.6%), and television (77.2%). Parents who had higher attitude
      scores toward influenza vaccine were 5 times as likely to report their adolescent
      had ever received influenza vaccine compared to parents who had lower attitude
      scores (adjusted odds ratio (aOR) 5.1; 95% confidence intervals (CI) 3.1-8.4; P <
      0.01). Parent vaccine-related attitudes were a significant mediator of the
      relationship between sources of information and vaccine receipt. In light of the
      low response rate and participation in an adolescent vaccination intervention,
      findings may not be generalizable to other populations. This study shows the
      importance of multiple sources of information in influencing parental decision
      making about influenza vaccine for adolescents. Harnessing the power of mass
      media and family members and friends as health advocates for influenza
      vaccination can potentially help increase vaccination coverage of adolescents.

PMID- 25996690
TI  - Hypertension-Management of Hypertensive Disorders of Pregnancy According to
      International Guidelines: A Panel Discussion (Case 3: Superimposed Preeclampsia).

PMID- 25996689
TI  - Comparison of safety of radial and femoral approaches for coronary
      catheterization in interventional cardiology.
AB  - BACKGROUND: The femoral approach has been the preferably used access in
      interventional cardiology as well for coronary diagnostics as for percutaneous
      coronary intervention, being perceived as easy and facilitating quick access with
      relatively low risk. Due to the results of the latest studies, however, the
      radial approach has become increasingly popular. The aim of this study was a
      safety analysis of cardiological interventional procedures (i.e., coronarography
      and PCI) according to the vessel approach. MATERIAL/METHODS: The 204 coronary
      interventions done in our Department of Interventional Cardiology were
      retrospectively analyzed. All the procedures were classified according to femoral
      or radial access. The incidence of local complications (e.g., major bleedings and
      hematomas) was assessed as well as the volume of contrast agent administered
      during the procedure and the radiation dose. RESULTS: It has been shown that
      radial approach, which is obviously more comfortable for patients, reduces the
      risk of local complications (0 vs. 2.97% and 0 vs. 3.96%) and does not lead to
      increased radiation exposure (p=0.88). However, there could be a larger volume of
      contrast agent administered (p=0.029), which in some cases could increase the
      risk of contrast-induced nephropathy. CONCLUSIONS: The radial approach should be
      recommended as a first choice because it is safer than the classical femoral
      approach, but one must be cautious in choosing radial approach patients with
      renal insufficiency.

PMID- 25996691
TI  - A Method of DTM Construction Based on Quadrangular Irregular Networks and Related
      Error Analysis.
AB  - A new method of DTM construction based on quadrangular irregular networks (QINs)
      that considers all the original data points and has a topological matrix is
      presented. A numerical test and a real-world example are used to comparatively
      analyse the accuracy of QINs against classical interpolation methods and other
      DTM representation methods, including SPLINE, KRIGING and triangulated irregular
      networks (TINs). The numerical test finds that the QIN method is the second-most
      accurate of the four methods. In the real-world example, DTMs are constructed
      using QINs and the three classical interpolation methods. The results indicate
      that the QIN method is the most accurate method tested. The difference in
      accuracy rank seems to be caused by the locations of the data points sampled.
      Although the QIN method has drawbacks, it is an alternative method for DTM
      construction. 

PMID- 25996692
TI  - Wheelchair-mounted robotic arm to hold and move a communication device - final
      design.
AB  - At the 51st Rocky Mountain Bioengineering Symposium we presented a preliminary
      design for a robotic arm to assist an individual living within an assistive
      technology smart home. The individual controls much of their environment with a
      Dynavox Maestro communication device. However, the device obstructs the
      individual?s line of site when navigating about the smart home. A robotic arm was
      developed to move the communication device in and out of the user?s field of view
      as desired. The robotic arm is controlled by a conveniently mounted jelly switch.
      The jelly switch sends control signals to a four state (up, off, down, off)
      single-axis robotic arm interfaced to a DC motor by high power electronic relays.
      This paper describes the system, control circuitry, and multiple safety features.
      The arm will be delivered for use later in 2015. 

PMID- 25996693
TI  - Changes in Saccadic Eye Movements produced by Novel Brain and Vestibular
      rehabilitation Therapy.
AB  - Saccadic eye movements offer several insights into the functional status of many
      areas of the central nervous system. As suchtheir observation is an important
      component of any neurological assessment. Unfortunately, these types of eye
      movementsare very fast and therefore cannot be evaluated in detail without high
      speed instrumentation. Direct infrared (IR) technologyallows to easily quantify
      standard saccades parameters such as latency, peak and mean velocity, and Q
      factor, as well as torecord the actual shape of the movement and its velocity.
      Using a direct IR device, we investigated if it is possible to changesaccades
      using a novel brain and vestibular rehabilitation therapy in subjects suffering a
      variety of neurological dysfunctions.Pre-post therapy comparison of saccade
      parameters showed that this type of subject's specific therapy can improve
      withstatistical significance the parameters of interest. However, the effects
      were not limited to the parameters of interest:subject-specific brain and
      vestibular rehabilitation therapy can improve the other parameters as well,
      although thisimprovement was not always statistically significant. Furthermore,
      we found that for the infrequent cases where thesubject-specific brain and
      vestibular rehabilitation therapy produced a deterioration of the other
      parameters, it was notstatistically significant. 

PMID- 25996694
TI  - Optimal tube length for the submerged printing of ovarian cancer cells.
AB  - Ovarian cancer is the fifth most common cancer affecting US women, killing more
      women each year than all other gynecologic cancers combined. Treatment of ovarian
      cancer is challenging with an overall 5-year survival rates of only 28-46% based
      on the metastatic state of the disease. While overall survival has improved with
      modern chemotherapy, poor outcomes have persisted. One of the greatest challenges
      in cancer therapeutic research remains that late-stage drug development trials
      for drug candidates have high attrition rates, up to 70% in Phase II and 59% in
      Phase III trials. The development of in vitro, high-throughput, cell based assays
      could provide a tool to overcome the challenges associated with high attrition
      rates by allowing for controlled cell deposition with a defined, controlled
      phenotype. Submerged, three-dimensional (3D) microfluidic printing technology is
      uniquely capable of controlling cell deposition without sacrificing the viability
      of cells for cell-based assays. Here, we investigate the phenotypic effects of
      tube length during printing on the cells. We observe that the length of the tube
      has minimal effects on the viability and density of A2780 ovarian cancer cells
      different cell lines. This study details foundational information for developing
      a high-throughput cell-based assays (CBA) for screening effective cancer drug
      candidates. 

PMID- 25996695
TI  - Comparison of submerged and unsubmerged printing of ovarian cancer cells.
AB  - A high-throughput cell based assay would greatly aid in the development and
      screening of ovarian cancer drug candidates. Previously, a three-dimensional
      microfluidic printer that is not only capable of controlling the location of cell
      deposition, but also of maintaining a liquid, nutrient rich environment to
      preserve cellular phenotype has been developed (Wasatch Microfluidics). In this
      study, we investigated the impact (i.e., viability, density, and phenotype) of
      depositing cells on a surface submerged in cell culture media. It was determined
      that submersion of the microfluidic print head in cell media did not alter the
      cell density, viability, or phenotype.. This article describes an in depth study
      detailing the impact of one of the fundamental components of a 3D microfluidic
      cell printer designed to mimic the in vivo cell environment. Development of such
      a tool holds promise as a high-throughput drug-screening platform for new cancer
      therapeutics. 

PMID- 25996696
TI  - Pathophysiological Effects of Thymoquinone and Epigallocatechin-3-Gallate on SK
      OV-3 Ovarian Cancer Like Cell Line.
AB  - Ovarian cancer is the leading cause of mortality among the gynecologic cancers
      and is the 5th most common cancer among women. Recent studies have indicated that
      antioxidant exposure may slow the progression in major neoplastic diseases. The
      objective of this study was to investigate the pathophysiological effects of
      Thymoquinone (TQ) and Epigallocatechin-3-gallate (EGCG) using the SK-OV-3 cell
      line as a model. A total of 72 wells were plated with (10^5) SK-OV-3 ovarian
      cancer cells according to standard lab protocols. Each group was subdivided into
      4 groups of 6 wells each. Group 1 served as control and groups 2, 3, and 4 were
      treated with TQ (16 uM), EGCG (3 ug/ml), and TQ + EGCG, respectively. Biomarker
      and morphological evaluations were performed following standard lab techniques.
      The results of the study revealed: (1) there were no differences in protein
      levels for all time periods (p<0.05); (2) an increase in nitric oxide following
      the administration of EGCG alone and in combination with TQ compared with TQ
      alone or untreated control cells with the difference being approximately three
      fold higher and this difference was statistically different (p<0.05) at 24, 48,
      72 hours; (3) glutathione levels were not statistically different at all time
      periods (p<0.05); and (4) the MDA levels showed no damage to the SK-OV-3 ovarian
      cancer cells. The results of this study provided the literature with more
      insights regarding manipulation of ovarian cancer behavior through potent
      antioxidants such as TQ and EGCG in culture. 

PMID- 25996697
TI  - Detecting daily activity of solitary living elderly persons.
AB  - We report on an activity monitoring system for elderly persons living alone.
      Caregivers would like to know whether the person is talking during their daily
      activity. Our monitoring system consists of a recorder and a personal computer.
      The recorder, attached to the subject's chest, employs two microphones, a tri
      axis accelerometer, two low-power amplifiers, a low-power microcomputer (MC) and
      a 2GB micro SD Memory Card (SDMC). One of the microphones is set in the direction
      of the chest for recording the person's voice, and the other microphone is set to
      the opposite side for recording surrounding sound. The microphone outputs and the
      accelerometer outputs are sent to the MC?s 10 bit analog to digital converters
      and sampled at 4000Hz and 50Hz, respectively. The MC detects the length of the
      conversation time from the microphone outputs, and the posture and behavior are
      detected from the accelerometer outputs every 5 seconds. The detected time,
      posture and behavior are stored in the SDMC. The data can be downloaded from the
      memory card and sent to appropriate stations. The system is used to monitor the
      health and physical conditions during daily life of elderly persons living alone.

PMID- 25996698
TI  - Human subject evaluation of the controlled resistance exercise device (C-red) for
      spaceflight.
AB  - Resistance exercise is an effective countermeasure to the muscle and bone atrophy
      associated with the unloading experienced during spaceflight. Long duration
      spaceflight will require compact exercise devices that are capable of delivering
      sufficient loading to prevent physiological losses while meeting strict mass and
      volume requirements. Accordingly, a controlled resistance exercise device (C
      RED), developed as an advanced exercise concept for NASA, uses an electric motor
      for resistance and is programmed to simulate inertial loading based on barbell
      acceleration and desired resistance mass. The barbell acts as a movable pulley
      increasing efficiency by doubling the created load. Human subject testing of the
      functionality of the device was conducted in a laboratory at NASA?s Johnson Space
      Center. Subjects performed ten resistance exercises typically used by astronauts
      at three freely chosen load levels. The results indicate that subjects were able
      to perform all exercises with resistance loads that were typical to those used in
      the gymnasium with loads ranges of 4-1600 N, and bilateral symmetry of ground
      reaction force was quantified for the deadlift. A survey also was given to each
      subject to allow the users to express their opinions regarding the device. The
      subject questionnaire showed that the dumbbell attachment exercises were
      preferred to the barbell exercises. The positive preliminary results indicate
      promise for the device. 

PMID- 25996699
TI  - Effect of tone-based sound stimulation on balance performance of normal subjects:
      preliminary investigation.
AB  - Sound is known to affect the human brain, hence sound or music therapy is
      sometimes used to improve a subject's physicaland mental health. In this study,
      the effects sound stimulation has on balance were investigated by means of
      computerizeddynamic posturography tests performed with eyes closed on an unstable
      surface using a CAPS(r) system, exceeding theInternational Society for Posture
      and Gait Research (ISPGR) recommended metrological performance standards.
      Subjectswere tested without listening to any music (baseline), listening to ?pure
      music?, and listening to the same music with differenttones embedded into it (one
      for each key). We found that different subjects react differently to different
      tones. Music alonedid not have a statistically significant effect on balance
      compared to the baseline, but the ?best? tone significantly improvedbalance
      compared to the baseline or the ?pure music? conditions. Furthermore, the ?worst?
      tone reduced the balancecompared to ?pure music?, but the reduction was not
      statistically significant relative to the baseline. The results thereforeindicate
      that, at least relative to balance performance, the tone-based sound stimulation
      we investigated is effective andinherently safe, but that tone selection depends
      on the individual subject. 

PMID- 25996700
TI  - Posturographic performance and repeatability of the computerized sit-to-stand
      test: preliminary results.
AB  - Each year, one in every three adults over the age of 65 falls often with injury.
      While this public health problem can be substantially reduced with simple
      interventions such as vestibular rehabilitation, balance assessments are not
      routinely done in the clinic, and less than half of affected adults talk to their
      physicians about such concerns. The goal of this study is to investigate distinct
      posturographic parameters of the computerized Sit-to-Stand (StS) Test to
      determine between- and within- subject variability of these. The CAPS(r)
      Professional system and the BalanceTRAK(r) software were used to collect ten
      repetitions of the StS from 25 subjects. The inclusion criteria included a
      questionnaire investigating the subject?s health status, the presence of known
      vestibular health concerns or illnesses, and the ability to maintain balance
      while standing. Significant variation between and within subjects were found for
      all posturographic parameters considered in this study. However, no fatigue or
      learning effects were found among the ten repetitions. 

PMID- 25996701
TI  - The bioengineering of changing lifestyle and wearable technology: a mini review.
AB  - Chronic diseases are a major health concern at the national and global level.
      According to the CDC, 86% of US health dollars go toward the treatment of chronic
      diseases. Many chronic diseases are manageable or preventable if individuals make
      appropriate lifestyle choices. Wearable technology ? both consumer and medical ?
      provides a unique opportunity to track lifestyle choices, such as increasing
      physical activity. It is estimated the market for consumer wearables will grow
      from $9.2 billion in 2014 to $30 billion by 2018. With such a potential market
      growth, it is important to understand the potential benefits and limitations of
      wearable technology to impact chronic disease management and prevention. 

PMID- 25996702
TI  - Optimal channels election for multi-Channels SVEP Detection and Classification in
      BCIS.
AB  - Many multi-channel techniques for Steady-State Visual-Evoked Potential (SSVEP)
      detection from EEG have shown significant improvement in the performance of Brain
      Computer Interfaces (BCIs). Multi-channel methods, generally involve deriving a
      spatial filter to linearly combine the EEG channels so as to minimize the noise
      energy and enhance the SSVEP response. In this paper, three state of the art
      multi-channel techniques are studied and compared. The performance of the
      classifiers for varying number and combination of the EEG channels is studied to
      determine the optimal choice of channels that yield maximum classification
      accuracy. The correlation of different channel parameters with the net montage
      performance is also investigated. Results indicate that Minimum Energy Channel
      (MEC) based classifier yields the highest accuracy values using 6 channels for
      all the 3 subjects. Significance of non-occipital locations for signal
      acquisition has been observed. Further, results indicate that the choice of
      channels to be used in the montage is to be made keeping in mind their
      effectivesignal strength, co-channel noise correlation values and signal to noise
      ratios. This ensures that a particular montage has effectively assimilated the
      signal and noise components. 

PMID- 25996703
TI  - Estimating cardiac output from blood pressure and heart rate: the liljestrand &
      zander formula.
AB  - Cardiac output (CO) is an important indicator of cardiovascular function. Several
      invasive and non-invasive methods have been developed and validated to assess CO
      in the clinical setting. These are often computationally complex or proprietarily
      restricted, and thus, not feasible in ambulatory investigations and the
      laboratory research setting. Simple mathematical transforms have been proposed to
      estimate CO from pulse pressure (PP = mean systolic blood pressure (SBP) minus
      mean diastolic blood pressure (DBP)), and mean heart rate (HR). Recently we
      evaluated one such simple technique [CO=(PPxHR)x.002], and found moderate
      correlation between the CO estimate and Modelflow-derived CO. Here we aimed to
      evaluate a more sophisticated formula, proposed in 1940 by Liljestrand and
      Zander. CO was estimated (COEST) dividing PP by the sum of SBP and DBP and
      multiplying the product by HR. This index was correlated with the Modelflow (3
      element Windkessel) -derived CO. Baseline beat-to-beat blood pressure data from
      67 young (mean age = 19.94+/- 2.8), healthy men (n = 30) and women (n = 37) was
      available for analysis. Overall, the correlation of COEST and CO was moderate (r
      = .42, p <.0001) and stronger in men (r = .66, p < .0001) compared to women (r =
      .36, p < .05). These results suggest that at least in some situations the
      Liljestrand and Zander method may provide an adequate measure of CO when other
      methods are not available. 

PMID- 25996704
TI  - Frailty Analysis of SEMG Signals for Different Hand Movements Based on Temporal
      and Spectral Approach.
AB  - Surface electromyography (sEMG) signal is the electrical manifestation of
      neuromuscular activities. It is an intricate signal that depends on the
      anatomical and physiological properties of the contracting muscles beneath the
      skin. In this work, a single channel surface EMG amplifier is designed to acquire
      the signals non-invasively from the skin by using bio-potential electrodes for
      three different hand movements. Subjects of age group 1 (18-30 years) and group 2
      (60-78 years) are considered for this analysis. The recorded signals are pre
      processed using Empirical Mode Decomposition (EMD) method to remove unwanted
      noises. Various error measures and performance index are calculated from the pre
      processed sEMG signals to compare the performance of EMD with conventional
      digital filters. Relevant time and frequency domain features are extracted from
      the pre-processed signals. It is observed that the statistical analysis performed
      over the extracted features show distinct variation between the age groups. Thus
      the methodology proposed in this work could be useful for the analysis of frailty
      especially for the subjects above 60 years. 

PMID- 25996705
TI  - Automatic Severity Assessment of Dysarthria using State-Specific Vectors.
AB  - In this paper, a novel approach to assess the severity of the dysarthria using
      state-specific vector (SSV) of phone-cluster adaptive training (phone-CAT)
      acoustic modeling technique is proposed. The dominant component of the SSV
      represents the actual pronunciations of a speaker. Comparing the dominant
      component for unimpaired and each dysarthric speaker, a phone confusion matrix is
      formed. The diagonal elements of the matrix capture the number of correct
      pronunciations for each dysarthric speaker. As the degree of impairment
      increases, the number of phones correctly pronounced by the speaker decreases.
      Thus the trace of the confusion matrix can be used as objective cue to assess
      di?erent severity levels of dysarthria based on a threshold rule. Our proposed
      objective measure correlates with the standard Frenchay dysarthric assessment
      scores by 74 % on Nemours database. The measure also correlates with the
      intelligibility scores by 82 % on universal access dysarthric speech database. 

PMID- 25996706
TI  - Identification of Onset Of Fatigue in Biceps Brachii Muscles Using Surface EMG
      and Multifractal DMA Alogrithm.
AB  - Prolonged and repeated fatigue conditions can cause muscle damage and adversely
      impact coordination in dynamic contractions. Hence it is important to determine
      the onset of muscle fatigue (OMF) in clinical rehabilitation and sports medicine.
      The aim of this study is to propose a method for analyzing surface
      electromyography (sEMG) signals and identify OMF using multifractal detrending
      moving average algorithm (MFDMA). Signals are recorded from biceps brachii
      muscles of twenty two healthy volunteers while performing standard curl exercise.
      The first instance of muscle discomfort during curl exercise is considered as
      experimental OMF. Signals are pre-processed and divided into 1-second epoch for
      MFDMA analysis. Degree of multifractality (DOM) feature is calculated from
      multifractal spectrum. Further, the variance of DOM is computed and OMF is
      calculated from instances of high peaks. The analysis is carried out by dividing
      the entire duration into six equal zones for time axis normalization. High peaks
      are observed in zones where subjects reported muscle discomfort. First muscle
      discomfort occurred in third and forth zones for majority of subjects. The
      calculated and experimental muscle discomfort zone closely matched in 72% of
      subjects indicating that multifractal technique may be a good method for
      detecting onset of fatigue. The experimental data may have an element of
      subjectivity in identifying muscle discomfort. This work can also be useful to
      analyze progressive changes in muscle dynamics in neuromuscular condition and co
      contraction activity. 

PMID- 25996707
TI  - Differentiating Muscle Fatigue and Nonfatigue Conditions Using Surface EMG
      Signals and Zhao-Atlas-Marks Based Time-Frequency Distribution.
AB  - Muscle fatigue is a neuromuscular condition where muscles fail to generate the
      required force. It occurs in normal as well as abnormal subjects. The analysis of
      muscle fatigue plays a significant role in the field of clinical studies, myo
      electric control, ergonomics and sports biomechanics. In this work, an attempt
      has been made to differentiate the sEMG signals under muscle non-fatigue and
      fatigue conditions using Zhao-Atlas-Marks (ZAM) based time frequency
      distribution. For this purpose, sEMG signals are recorded from fifty healthy
      volunteers during isometric contractions under well defined protocol. The
      acquired signals are preprocessed and subjected to ZAM based time-frequency
      analysis. The time-frequency based features such as instantaneous median
      frequency (IMDF) and instantaneous mean frequency (IMNF) are extracted from the
      time-frequency spectrum. The results show that IMDF and IMNF are distinct for
      muscle non-fatigue and fatigue conditions. Further, more number of frequency
      components are observed in the time-frequency spectrum of signals recorded in
      nonfatigue conditions. The t-test performed on these features has shown
      significant difference (p<0.01) in between non-fatigue and fatigue conditions.
      Thus the study seems to be useful for the analysis of various neuromuscular
      conditions. 

PMID- 25996708
TI  - Effects Of Polylactic Acid Coating and Compression Load on the Delivery of
      Protein and Steroid from HA Ceramic Devices.
AB  - Density variations, due to particle size and time and temperature of sintering,
      affect the delivery profile of substances from ceramic delivery devices. This
      investigation was conducted to study the effect of polylactic acid (PLA)
      impregnation on the porosity of hydroxyapatite (HA) capsules by studying the
      delivery rate of bovine serum albumin (BSA) and testosterone (TE). HA capsules
      were fabricated by cold compressing calcined particles at 1000, 3000, and 5000
      lbs. Each group was subdivided into PLA-impregnated and non-PLA impregnated
      capsules. Each capsule was loaded with either 40 mg of TE (impregnated or
      nonimpregnated with PLA polymer) or BSA. Data obtained in this study suggest
      that: (1) PLA impregnation of HA ceramic capsules decreases the rate of release
      of drugs from the ceramic reservoir, (2) Physiochemical characteristics of the
      drugs to be delivered is an instrumental key in the sustained release profiles,
      (3) Compression load of HA reservoirs is a key factor in predicting the duration
      and level of sustained delivery, and (4) Polymer coating of HA ceramic capsules
      reduces the pore size, as well as, blocking some of the pores on the surface. 

PMID- 25996709
TI  - The Resultant Physiological Effects of Human Gingival Fibroblasts Exposed to
      Combinations of Dental Adhesives, Porphyromonas Gingivalis Lipopolysaccharide,
      and Cortisol or Nifedipine.
AB  - The needs of dental patients are becoming ever complex. This is largely due to
      the increasing number of systemic conditions that patients present with during
      routine or emergency dental visits, such as hypertension and angina pectoris.
      Medications that patients are prescribed have potential to cause effects on the
      oral tissues. There is a need to understand the interactions between the oral
      tissues and materials used to restore teeth. The objective of this study was to
      assess the physiological function of human gingival fibroblasts upon exposure to
      dental adhesives; polymethyl methacryate, OptiBond(r), and Prime & Bond(r);
      Porphyromonas gingivalis lipopolysaccharide and Cortisol or Nifedipine. An
      increase in metabolic activity was noted with the experimental group exposed to
      the combination of Prime & Bond(r), LPS-PG, and Nifedipine (P<0.001). Oxidative
      stress was observed in experimental groups exposed to the combinations of PMMA,
      LPS-PG, and Cortisol (P<0.001); also noted in all three dental adhesives in
      combinations with LPS-PG and Nifedipine (P<0.001). Cellular membrane damage was
      evident in experimental groups exposed to the combinations of PMMA, LPS-PG, and
      Cortisol; PMMA, LPS-PG, and Nifedipine; and Prime & Bond(r), LPS-PG, and
      Nifedipine. In conclusion, it appears that the addition of Nifedipine in
      combination with LPS-PG negatively alters cellular function by causing membrane
      damage and inducing oxidative stress. 

PMID- 25996710
TI  - Sustained Release of Demineralized Bone Matrix Protein in Osteoporotic Rats.
AB  - Demineralized bone matrix protein (DBM) was considered highly effective in
      stimulating bone healing. The objective of the study was to explore the use of
      tricalcium phosphate (TCP) delivery system to continuously deliver DBM in an
      osteoporotic condition and to evaluate changes in bone density and preservation
      of the spine. Ovariectomized Sprague Dawley rats were divided into three equal
      groups (n=16 per group). Animals in group I served as control, animals in groups
      II and III were surgically implanted with either empty (SHAM) or DBM filled TCP
      implants adjacent to L4/L5. Eight animals from each group were euthanized at 2
      and 8 weeks post implantation. Femurs were evaluated for changes in density, and
      the lumbar spine was evaluated for changes in the endplate. Results of this study
      revealed (1) TCP implants were capable of delivering DBM for long duration, (2)
      use of sustained delivery of DBM did not induce untoward effects in the vital
      organs or in the uterus, fallopian tubes, or vaginal tissues, (3) DBM had no
      effect on chondrocyte differentiation in the spine, and (4) DBM did not increase
      bone density in osteoporotic female rats. 

PMID- 25996711
TI  - Effects of Filtering on Experimental Blast Overpressure Measurements.
AB  - When access to live-fire test facilities is limited, experimental studies of
      blast-related injuries necessitate the use of a shock tube or Advanced Blast
      Simulator (ABS) to mimic free-field blast overpressure. However, modeling blast
      overpressure in a laboratory setting potentially introduces experimental
      artifacts in measured responses. Due to the high sampling rates required to
      capture a blast overpressure event, proximity to alternating current (AC-powered
      electronics) and poorly strain-relieved or unshielded wires can result in
      artifacts in the recorded overpressure trace. Data in this study were collected
      for tests conducted on an empty ABS (?Empty Tube?) using high frequency pressure
      sensors specifically designed for blast loading rates (n=5). Additionally,
      intraocular overpressure data (?IOP?) were collected for porcine eyes potted
      inside synthetic orbits located inside the ABS using an unshielded miniature
      pressure sensor (n=3). All tests were conducted at a 30 psi static overpressure
      level. A 4th order phaseless low pass Butterworth software filter was applied to
      the data. Various cutoff frequencies were examined to determine if the raw shock
      wave parameters values could be preserved while eliminating noise and artifacts.
      A Fast Fourier Transform (FFT) was applied to each test to examine the frequency
      spectra of the raw and filtered signals. Shock wave parameters (time of arrival,
      peak overpressure, positive duration, and positive impulse) were quantified using
      a custom MATLAB(r) script. Lower cutoff frequencies attenuated the raw signal,
      effectively decreasing the peak overpressure and increasing the positive
      duration. Rise time was not preserved the filtered data. A CFC 6000 filter
      preserved the remaining shock wave parameters within +/-2.5% of the average raw
      values for the Empty Tube test data. A CFC 7000 filter removed experimental high
      frequency artifacts and preserved the remaining shock wave parameters within +/
      2.5% of the average raw values for test IOP test data. Though the region of
      interest of the signals examined in the current study did not contain extremely
      high frequency content, it is possible that live-fire testing may produce shock
      waves with higher frequency content. While post-processing filtering can remove
      experimental artifacts, special care should be taken to minimize or eliminate the
      possibility of recording these artifacts in the first place. 

PMID- 25996712
TI  - Experimental Characterization of the Anatomical Structures of the Lumbar Spine
      Under Dynamic Sagittal Bending.
AB  - Underbody blast (UBB) events transmit high-rate vertical loads through the seated
      occupant?s lumbar spine and have a high probability of inducing severe injury.
      While previous studies have characterized the lumbar spine under quasi-static
      loading, additional work should focus on the complex kinetic and kinematic
      response under high loading rates. To discern the biomechanical influence of the
      lumbar spine?s anatomical structures during dynamic loading, the axial force,
      flexion-extension moments and range of motion for lumbar motion segments (n=18)
      were measured during different states of progressive dissection. Pre-compression
      was applied using a static mass while dynamic bending was applied using an offset
      drop mass. Dynamic loading resulted in peak axial loads of 4,224+/-133 N, while
      maximum peak extension and flexion moments were 19.6+/-12.5 and -44.8+/-8.6 Nm in
      the pre-dissected state, respectively. Upon dissection, transection of the
      interspinous ligament, ligamentum flavum and facet capsules resulted in
      significantly larger flexion angles, while the removal of the posterior elements
      increased the total peak angular displacement in extension from 3.3+/-1.5 to
      5.0+/-1.7 degrees (p=0.002). This study provides insight on the contribution of
      individual anatomical components on overall lumbar response under high-rate
      loading, as well as validation data for numerical models. 

PMID- 25996713
TI  - A Method to Quantify Supine to Prone Thoracoabdominal Deformation and Organ
      Migration in a Set of Healthy Young Adults.
AB  - Medical image data used for the development of computational human body models
      are often retrospectively acquired, and researchers are unlikely to encounter
      scans of healthy individuals in specific postures. We prospectively acquired
      scans in both prone and supine postures from 22 healthy young adults; M:F 1:1,
      with age, height, and weight of 28.8+/-7.0 years, 173.0+/-7.8 cm, and 70.6+/-10.9
      kg. While prone, subjects? arms were superior to the head and supported by a foam
      insert at axilla. Breath held, T1-weighted MRI scans were acquired using a
      Siemen?s Skyra 3T with an in-plane resolution of 1.56 mm (TR: 4.10 ms, TE: 1.23
      ms, thickness: 2 mm, matrix: 256x256, FOV: 400 mm). Gross thoraco-abdominal
      compression was considered as the change in perpendicular distance in the
      transverse plane measured from the anterior margin of L4/L5 to the table (for
      prone) or exterior body surface (for supine). Gross thoraco-abdominal, liver and
      spleen compression were found to be 8.5% (71.6+/-12.9 mm prone vs. 78.7+/-12.4 mm
      supine; p=0.0013), 17.7% (110.4+/-4.1 mm prone vs. 134.8+/-2.6 mm supine;
      p<0.0001), and 3.5% (53.8+/-1.9 mm prone vs. 57.3+/-2.9 mm supine) respectively.
      Gender and spleen compression differences were not noted. The liver and spleen
      migrated on average 8.3 mm posteriorly, 11.4 mm rightward, 15.1 mm superiorly and
      4.1 mm anteriorly, 6.1 mm rightward, 1.7 mm superiorly respectively. The data
      obtained from this set may be of use in computational biomechanics, surgical
      simulation, and medical device design. 

PMID- 25996714
TI  - Automated Measurement Technique for the Determination of Regional Skull and Scalp
      Constituent Thickness.
AB  - The human skull is a multi-layered composite system critical in protecting the
      brain during head impact. Head impact studies investigating skull injury
      thresholds have suggested that the skull and scalp thickness affect the risk of
      fracture. Therefore, accurately determining the dimensions of skull-scalp
      constituents is a necessary step in attributing the contribution to response,
      failure mechanisms and in developing high fidelity human models. However, prior
      methods to collect these data include physical measurements of biopsies and
      manual segmentation in X-ray images. These methods are invasive and impractical
      for clinical applications, or insufficient to characterize the regional variance
      in the skull-scalp constituents for a full mechanical strength characterization.
      The newly developed methods in this study describe an automated, regional, and
      objective-based measurement technique to characterize the average thickness and
      variance in skull and scalp constituents using quantitative computed tomography
      (QCT). The developed approach was successfully employed on 7 specimens at 5
      anatomically defined locations. Results report the thicknesses for each layer,
      with the layer of greatest variation being the trabecular bone (diploe) having a
      standard deviation of 35.6% of its mean thickness. These results will be used to
      define skull morphology for modeling relative impact injury risk that will be
      experimentally validated. 

PMID- 25996715
TI  - Skull Thickness Morphing for an Age and Sex Specific FE Model of the Skull.
AB  - Skull deformation is believed to be a contributing factor in traumatic brain
      injury (TBI). Furthermore, skull thickness is thought to be an important factor
      governing deformation of the skull and its susceptibility to fracture. Although
      many studies have been done to understand the mechanisms of brain injury and
      skull fracture, the majority of the cadaveric and finite element (FE) modeling
      efforts are comprised of older males and 50th percentile male skulls,
      respectively, which do not accurately represent the population as a whole. This
      study employed a set of skull table thickness regressions defined at homologous
      landmarks on the skull which were calculated from 123 pre-existing head CT scans
      (ages 20-100) using a cortical density-based algorithm. A method was developed to
      morph the Global Human Body Models Consortium (GHBMC) 50th percentile male skull
      model to age and gender specific geometries based on the full thickness
      regressions using a Thin Plate Spline algorithm. A quantitative measure of
      morphing error was devised and measured using the morphed and desired full
      thickness values at the homologous landmark locations. This methodology can be
      used to create gender and age-specific FE models of the skull and will ultimately
      be used to understand the relationship between cortical thickness, skull
      deformation, and head injury. 

PMID- 25996716
TI  - Mesh Smoothing Algorithm Applied to a Finite Element Model of the Brain for
      Improved Brain-Skull Interface.
AB  - The brain-skull interface plays an important role in the strain and pressure
      response of the brain due to impact. In this study, a finite element (FE) model
      was developed from a brain atlas, representing an adult brain, by converting each
      1mm isotropic voxel into a single element of the same size using a custom code
      developed in MATLAB. This model includes the brain (combined cerebrum and
      cerebellum), cerebrospinal fluid (CSF), ventricles, and a rigid skull. A voxel
      based approach to develop a FE model causes the outer surface of each part to be
      stair-stepped, which may affect the stress and strain measurements at interfaces
      between parts. To improve the interaction between the skull, CSF, and brain
      surfaces, a previously developed mesh smoothing algorithm based on a Laplacian
      non-shrinking smoothing algorithm was applied to the FE model. This algorithm not
      only applies smoothing to the surface of the model, but also to the interfaces
      between the brain, CSF, and skull, while preserving volume and element quality.
      Warpage, jacobian, aspect ratio, and skew were evaluated and reveal that >99% of
      the elements retain good element quality. Future work includes implementation of
      contact definitions to accurately represent the brain-skull interface and to
      ultimately better understand and predict head injury. 

PMID- 25996717
TI  - Comparison of Slip Training in VR Environment And on Moveable Platform.
AB  - Slip training is gaining popularity as an innovative fall intervention approach.
      The objective of this study was to compare the efficacy of two different slip
      training modality (moveable platform and virtual reality) in reducing fall
      frequency and improving reactive recovery in older adults. Thirty-six healthy
      older adults were involved in a laboratory study, and were equally and randomly
      divided into the control group, the moveable platform training (MPT) group, and
      the virtual reality training (VRT) group. The MPT was achieved by inducing slips
      using a custom built sliding device consisting of a low friction, motorized
      moveable platform. The VRT was conducted by inducing visual perturbation in a
      head mounted display while subjects walked on a treadmill. All groups performed
      slip trials (kinematics, kinetics and EMG data were collected) on an actual
      slippery floor surface before and after a training session. The results indicated
      a significant reduction in fall frequency in both training groups. Between MPT
      and VRT groups, significant differences were also found in forward trunk
      rotations, peak knee angular velocity, ankle coactivity, and muscular activity in
      tibialis anterior. It was concluded that slip training in VR environment could
      produce comparable results in fall intervention. 

PMID- 25996718
TI  - Evaluation of Fall Recovery and Gait Adaptation to Medial and Lateral Gait
      Perturbations.
AB  - The aim of this study was to develop an active gait perturbation system and to
      evaluate its efficacy in evaluating fall recovery and gait adaptation. We
      hypothesized that a translating perturbation during the single stance phase would
      alter gait adaptations, in terms of gait parameters and muscle co-contractions,
      during recovery to maintain dynamic stability for continued walking. A customized
      miniature treadmill, built on a large force plate and embedded perpendicular to
      the walkway, was used to translate the loaded stance foot medially and laterally
      to interrupt swing foot trajectory. The perturbation was activated when the
      stepping foot was placed entirely on the belt to ensure the foot would remain on
      the belt when translated. The translating floor surface was applied to 10 young,
      healthy adult subjects (5 males, 5 females; aged <35y) during normal walking at
      their preferred speed. Step length, step width, step duration, and muscle co
      contraction at the ankle of the stance limb was examined before, during, and
      after both the medial and lateral translations. Shorter step length, wider step
      width, faster step duration, and higher muscle co-contraction at the ankle joint
      were observed strategies for fall recovery and regaining body stability. 

PMID- 25996719
TI  - Material Parameter Determination of an L4-L5 Motion Segment Finite Element Model
      Under High Loading Rates.
AB  - Underbody blast (UBB) events impart vertical loads through a victim?s lumbar
      spine, resulting in fracture, paralysis, and disc rupture. Validated biofidelic
      lumbar models allow characterization of injury mechanisms and development of
      personal protective equipment. Previous studies have focused on lumbar mechanics
      under quasi-static loading. However, it is unclear how the role and response of
      individual spinal components of the lumbar spine change under dynamic loading.
      The present study leverages high-rate impacts of progressively dissected two
      vertebra lumbar motion segments and Split-Hopkinson pressure bar tissue
      characterization to identify and validate material properties of a high-fidelity
      lumbar spine finite element model for UBB. The annulus fibrosus was modeled as a
      fiber-reinforced Mooney-Rivlin material, while ligaments were represented by
      nonlinear spring elements. Optimization and evaluation of material parameters was
      achieved by minimizing the root-mean-square (RMS) of compressive displacement and
      sagittal rotation for selected experimental conditions. Applying dynamic based
      material models and parameters resulted in a 0.42% difference between predicted
      and experiment axial compression during impact loading. This dynamically
      optimized lumbar model is suited for cross validation against whole-lumbar
      loading scenarios, and prediction of injury during UBB and other dynamic events. 

PMID- 25996720
TI  - Effects of Hydrostatic Pressure Exposure on Hepatic Progenitor Cells.
AB  - Hepatic progenitor cells (HPCs) have the potential to regenerate healthy tissue
      in the setting of chronic liver disease. The goal of this study was to
      characterize the mechanosensitivity of HPCs to sustained hydrostatic pressure (20
      mmHg) similar to that observed in liver cirrhosis. Bipotential Murine Oval Liver
      (BMOL) cells, an HPC-like cell line, were cultured in a hydrostatic pressure
      controlled chamber at 37 degrees C and 5% CO2 for 4 days (to 90% confluency) or
      12 days (superconfluency). Controls were run for each time point in a standard
      incubator without pressure. Nuclei were stained with DAPI and cells were viewed
      under a Zeiss 710 laser scanning confocal microscope with 40x objective. Nuclei
      were measured with Image J software (170 to 398 distinct cell nucleus area
      measurements per group). Two-way ANOVA was used to examine the influence of
      pressure and confluency on nuclear size. Cells exposed to pressure (mean nuclear
      area 126.7um2, S.D. 56.9) had significantly larger nuclei than control cells
      (mean nuclear area 102.3um2, S.D. 84.1), p<.001. The pressure*confluency
      interaction was also significant (p<.05). Results suggest that HPCs are sensitive
      to low-level hydrostatic pressure associated with chronic liver disease. Further
      experiments include analyzing cellular proliferation, morphology, and
      differentiation effects associated with pressure exposure. 

PMID- 25996721
TI  - Methodology to Calibrate Disc Degeneration in the Cervical Spine During Cyclic
      Fatigue Loading.
AB  - Prolonged exposure to vibrational working conditions can cause neck, back, and
      shoulder pain. Mechanical degradation of soft tissues resulting from this type of
      fatigue was experimentally shown to contribute to endplate and compression
      fractures. However, effects of repetitive subfailure loading on intervertebral
      disc (IVD) behavior have not been well defined. This manuscript describes a
      methodology to experimentally characterize changes in cervical spine IVD material
      properties under fatigue. Bone-disc-bone spinal units with intact ligaments
      obtained from human cervical spines were obtained and a lack of bony or soft
      tissue degeneration was confirmed using X-ray and MRI scans. Cranial and caudal
      specimen extents were fixed in PMMA to facilitate attachment to testing devices.
      Baseline response was quantified using flexion/extension pure moment protocols.
      Specimens were immersed in a 34-deg-C saline bath and allowed to acclimate for
      one hour. A stress-relaxation test was then performed and viscoelasticity
      quantified using a quasi linear viscoelastic (QLV) material model. Fatigue
      testing was performed for up to 50,000 cycles with intermittent viscoelasticity,
      pure moment testing, and imaging scans performed to quantify cycle-dependent
      changes in disc properties. Preliminary results demonstrated progressive changes
      in viscoelasticity and bending response of cervical spine segments with
      increasing number of load cycles. This procedure will be used to quantify
      degradation of the IVD under repetitive compressive loads, focusing on effects of
      loading magnitude and frequency. 

PMID- 25996722
TI  - Hybrid III Lower Leg Injury Assessment Reference Curves Under Axial Impacts Using
      Matched-Pair Tests.
AB  - The objective of the present study was to derive injury probability curves
      applicable to the Hybrid III dummy (also termed the Anthropomorphic Test Device,
      ATD) lower leg under axial impacts for military applications. A matched-pair
      approach was used. Axial impacts were delivered to below knee foot-ankle complex
      preparations of the lower leg of the ATD using pendulum and custom vertical
      accelerator devices. Military boot was used in some tests. Post mortem human
      surrogate (PMHS) preparations were used as matched-pair tests for injury
      outcomes. The alignment was such that the foot-ankle complex was orthogonal to
      the leg (below knee tibia-fibula complex), termed as the normal 90-90 posture.
      Injury outcomes from the biological surrogate focused on calcaneus and or distal
      tibia fractures with or without the involvement of articular surfaces. Peak lower
      tibia load cell forces were obtained from matched-pair dummy tests. Injury and
      force data were paired, censoring was assigned based on injury outcomes and
      survival analysis was done using the Weibull distribution to derive dummy-based
      probability curves. Mean peak forces were extracted at 5, 10, 20 and 50%
      probability levels. Normalized confidence interval sizes (NCIS) at +/- 95% level
      were computed to determine the tightness-of-fit of the confidence bands. The NCIS
      data ranged from 0.34 to 0.78 and a peak force of 8.2 kN was associated at the
      ten percent injury probability level. Other data and curves are given in the body
      of the paper. The present Injury Assessment Reference Curves and Values (IARC and
      IARV) may be used in future tests for advancing safety in military environments.
      These survival analysis processes and IARC and IARV data may also be used in
      other applications. 

PMID- 25996723
TI  - Analysis of Surface EMG Signals in Isometric Contraction at Different Angles
      Using Rainflow Counting Algorithms.
AB  - Endurance and muscle strengthening are required in a number of applications
      including fitness training, sports and prosthetics. Optimal performance can be
      achieved by understanding the relationship between muscle activity and angular
      variation of the elbow joint. Biceps brachii is an important muscle of the upper
      arm that helps in providing stability during flexion and extension. In this work,
      an attempt is made to analyze isometric contraction at various elbow angles using
      surface electromyography and rainflow counting algorithm. The signals are
      recorded from biceps brachii muscles of twenty healthy subjects while performing
      well defined protocol using a 6kg dumbbell at three different angles: 30 degrees
      , 60 degrees  and 90 degrees . The recorded signals are preprocessed and
      subjected to rainflow counting algorithm to obtain rainflow cycles. A new
      feature, cycle crossing intensity (CCI) is calculated from the rainflow cycles.
      The intensity peak parameter is computed from each CCI. The results show that the
      CCIs are distinct for all the three angles of elbow flexion and shifts towards
      higher magnitude values with increase in the angle of flexion. The average peak
      intensity is 425, 1073 and 2336 for 30 degrees , 60 degrees  and 90 degrees 
      respectively. This feature is found to have high statistical significance for 30
      degrees -90 degrees  flexion and 60 degrees -90 degrees  elbow flexion. The
      results shows that this method is useful in understanding muscle contractions at
      various angles of elbow joint. This technique can be extended to analyze muscles
      in neuromuscular conditions such as fatigue. 

PMID- 25996724
TI  - Analysis Of SEMG Signal Complexity Associated with Fatigue Conditions in Biceps
      Brachii Muscle using Multiscale Approximate Entropy.
AB  - Muscle fatigue is a neuromuscular condition which causes a decline in muscle
      performance. Surface electromyography (sEMG) signals are widely used to evaluate
      muscle fatigue and these signals are highly complex in nature. To address this,
      advanced signal processing techniques are necessary. In this work, an attempt has
      been made to analyze the complexity of sEMG signals associated with fatigue
      conditions using Multiscale Approximate Entropy (MSApEn) technique. Signals are
      recorded from biceps brachii muscles of fifty healthy subjects while performing
      curl exercise and it is divided into six equal segments to avoid variability in
      endurance time. The first and last segments are considered as nonfatigue and
      fatigue conditions respectively. The signals are preprocessed and MSApEn is
      evaluated. Further, four features namely median (MED), variance (VAR), high scale
      sum (HSS) and low scale sum (LSS) are extracted from each segment. The results
      indicate a distinct variation in the MSApEn values. It is found that the signals
      are complex in both fatigue and nonfatigue conditions. In addition, features
      namely the MED, HSS and LSS are found to be low in fatigue case. The t-test
      performed on these features shows high statistical significance (p-value<0.005).
      It appears that this method can be used to analyze the complexity of sEMG signals
      in varied clinical conditions. 

PMID- 25996725
TI  - Preliminary Development and Validation of an Atlas-Based Finite Element Brain
      Model.
AB  - Traumatic brain injury (TBI) is a leading cause of disability and injury-related
      death, accounting for nearly one third of all injury-related deaths. To prevent
      and understand these types of injuries, finite element models can be employed. In
      this study, an anatomically accurate finite element model was developed from the
      International Consortium for Brain Mapping (ICBM) using a voxel-based mesh
      generation approach. The aim of this study was to compare relative brain
      displacement of the atlas-based brain model (ABM) to cadaveric data. In these
      experiments, neutral density targets (NDTs) were implanted in the brain and their
      relative motion with respect to the skull was recorded. The same boundary
      conditions were applied to ABM and the relative displacements of the nodes
      nearest to the physical location of each NDT were computed. Initial simulation
      and validation show good agreement with experimental data. The data obtained in
      this study and further development of this model will help us understand the
      biomechanics of head injury as well as provide a tool to predict and prevent
      brain injury. 

PMID- 25996726
TI  - Managing Medical Device Incident Investigations.
AB  - When medical device-related incidents occur in the clinical environment, it?s
      important for the healthcare organization to respond quickly and effectively.
      This paper outlines seven steps that will help the organization conduct an
      investigation that will protect its interests, comply with federal regulations
      and accreditation standards, and improve patient safety by avoiding recurrences.
      The paper emphasizes the role of engineering design in reducing the likelihood
      and impact of medical device-related incidents. 

PMID- 25996727
TI  - A Clinical Study to Validate the Pupil Rescaling Technique by using COAS Shack
      Hartmann Aberrometer.
AB  - In any optical system, optical aberrations of the imaging system affect the image
      quality. The human eye is also like an optical system which has optical
      aberrations influencing the quality of the retinal image. When pupil size exceeds
      3 mm, ocular aberrations increase and play a major role on retinal image
      degradation. Pupil diameter is made constant in commercially available
      aberrometers by mathematically rescaling it. The aim of this study is to validate
      the pupil rescaling technique by using COAS (Complete Ophthalmic Analysis
      System)Shack Hartmann Aberrometer. Five subjects were recruited for this study.
      The measurements were taken over a moderately large pupil of 5mm in normal room
      illumination to allow for natural pupil dilation. The analyses diameter is fixed
      at 5 mm in COAS which means it rescales the aberration data to 5 mm if the pupil
      diameter recorded was more than 5 mm at the time of measurement. Ocular
      aberrations for natural and rescaled pupil sizes were analyzed. Estimation of
      ocular aberrations showed there was no statistical significance between natural
      pupil and rescaled pupil diameter. 

PMID- 25996728
TI  - Design of Content Based Image Retrieval Scheme for Diabetic Retinopathy Images
      using Harmony Search Algorithm.
AB  - Diabetic Retinopathy (DR) is a disorder that affects the structure of retinal
      blood vessels due to long-standing diabetes mellitus. Automated segmentation of
      blood vessel is vital for periodic screening and timely diagnosis. An attempt has
      been made to generate continuous retinal vasculature for the design of Content
      Based Image Retrieval (CBIR) application. The typical normal and abnormal retinal
      images are preprocessed to improve the vessel contrast. The blood vessels are
      segmented using evolutionary based Harmony Search Algorithm (HSA) combined with
      Otsu Multilevel Thresholding (MLT) method by best objective functions. The
      segmentation results are validated with corresponding ground truth images using
      binary similarity measures. The statistical, textural and structural features are
      obtained from the segmented images of normal and DR affected retina and are
      analyzed. CBIR in medical image retrieval applications are used to assist
      physicians in clinical decision-support techniques and research fields. A CBIR
      system is developed using HSA based Otsu MLT segmentation technique and the
      features obtained from the segmented images. Similarity matching is carried out
      between the features of query and database images using Euclidean Distance
      measure. Similar images are ranked and retrieved. The retrieval performance of
      CBIR system is evaluated in terms of precision and recall. The CBIR systems
      developed using HSA based Otsu MLT and conventional Otsu MLT methods are
      compared. The retrieval performance such as precision and recall are found to be
      96% and 58% for CBIR system using HSA based Otsu MLT segmentation. This automated
      CBIR system could be recommended for use in computer assisted diagnosis for
      diabetic retinopathy screening. 

PMID- 25996729
TI  - Regional Variation of Gap Junction Conductance on Reentrant Arrhythmia.
AB  - Arrhythmia generating conditions like ventricular hypertrophy, myocardial
      infarction or ischemia modify the intercellular coupling by modifying the
      conductance of gap junctions in the normal electric propagation pathway of the
      heart. A discrete ventricular cell network of 100x100 cells interconnected using
      resistive gap junctions is simulated to study the effect of size, shape and
      position of inhomogeneity as well as the value of gap junction conductance of
      inhomogeneity on the occurrence of reentrant arrhythmia. In addition to lowering
      the conduction, a unidirectional block is also created using exactly timed
      stimulation inputs thus setting the ideal conditions for a reentrant activation
      to arise from the zone of varied gap junction conductance. The shape and
      endurance of generated reentrant waves is analyzed. The electrical activity of
      each cell is simulated using the Ten Tusscher ?Panfilov 2006 model. Simulation
      results show that the positions as well as the size of the inhomogeneity play a
      major role in the creation of reentrant waves while the shape of the
      inhomogeneity does not have a significant effect. Also, reentrant waves occur at
      a certain level of decoupling. Too much or too little decoupling also doesn?t
      induce reentrant waves. The amplitude and duration of action potential is heavily
      dependent on the gap junction conductance. 

PMID- 25996730
TI  - In-Home Behavioral Monitoring Using Simultaneous Localization and Activity
      Detection.
AB  - Shifting demographics in the U.S. has created an urgent need to reform the
      policies, practices, and technology associated with delivering healthcare to
      geriatric populations. Automated monitoring systems can improve the quality of
      life while reducing healthcare costs for individuals aging in place. For these
      systems to be successful, both activity detection and localization are important,
      but most existing research focuses on only one of these technologies and systems
      that do collect both data treat these data sources separately. Here, we present
      SLAD {Simultaneous Localization and Activity Detection a novel framework for
      simultaneously processing data collected from localization and activity
      classification systems. Using a hidden Markov model and machine learning
      techniques, SLAD fuses these two sources of data in realtime using a
      probabilistic likelihood framework, which allows activity data to refine
      localization, and vice-versa. To evaluate the system, a wireless sensor network
      was deployed to collect RSSI data and IMU data concurrently from a wrist-worn
      watch; the RSSI data was processed using a radial basis function neural network
      localization algorithm, and the resulting position likelihoods were combined with
      the likelihoods from an IMU acitivty classification algorithm. In an experiment
      conducted in an indoor office environment, the proposed method produces 97%
      localization accuracy and 85% activity classification. 

PMID- 25996731
TI  - Characterization of Lumbar Spine Annular Disruption in PMHS Using MRI,
      Cryomicrotomy and Histology Techniques.
AB  - Internal intervertebral disc disruption is involved in the onset of a wide range
      of spinal dysfunction, ultimately affecting not only the disc itself but the
      surrounding osseous and neural structures as well. The ability of disc to
      withstand and effectively distribute axial load is dependent upon whether
      peripherally located annular fibers provide the support necessary to contain and
      corral the pressure sensitive nucleus. Any alteration in the structures immediate
      to the nucleus jeopardize this ability. While annular tears and fissures have
      been thoroughly investigated, one form of internal disc disruption is less well
      understood. A network of elastin cross-bridges provides resistance to
      delamination of the collagenous sheets that comprise the annulus. The current
      investigation utilized a Nitrogen gas-induced pressure mechanism to disrupt
      elastin cross links that exist between annular lamellae. Twenty five cadaveric
      lumbar spine motion segments (mean age: 52+/-12 yr.) were subjected to the
      annular disruption protocol. Damage to the annulus was assessed using MRI,
      cryomicrotome and histological staining procedures. MRI images were compared to
      cryomicrotome images to determine the ability of standard clinical MRI scans to
      determine annular damage. In many cases MRI was moderately revealing in terms of
      damage. Future studies will quantify biomechanical consequences of these low
      level annular disruptions relative to segmental stability. 

PMID- 25996732
TI  - Interaction of Radio Frequency and LAMBDA-DNA.
AB  - With the prevalence of wireless radio frequency (RF) devices, interest is growing
      to more fully understand the effect of RF on biological tissue. This research
      explores how ?DNA interacts with RF energy. By sweeping a radio frequency range
      from 1 GHz to 8.5 GHz we hope to observe if specific frequencies show
      significantly elevated RF energy-?DNA interaction (e.g. either absorbed and/or
      reflected). Our procedure is as follows: 1) Set up RF equipment (horn antennas
      and network analyzer), 2) vary frequency from 1- 8.5GHz at a RF power level of 0
      dBm, 3) vary same frequency sweep with buffer in the cell culture wells, and next
      with DNA and buffer in the cell-culture wells, and 4) the frequency sweep was
      repeated 100 times with a duration of 1.0 second per sweep. The results indicate
      regions of RF- ?DNA interaction around 3 and 3.5 GHz. 

PMID- 25996733
TI  - Ependymal Proliferation: A Conduit for Tricking the Central Nervous System into
      Bioengineering Itself.
AB  - Ependymal Cells are a type of Glial Cell lining the ventricles and central canal
      of the spinal cord. Their primary function is to secrete and circulate
      cerebrospinal fluid (CSF). Neural stem cells (NSC) exist within the ependymal
      lining that are capable of neurogenesis. Historically it was thought that
      neurogenesis only occurred prenatally and that adult ependymal cells are
      incapable of regeneration. It is now known that primary neurogenic areas within
      the Central Nervous System (CNS) are located within the lateral ventricle and
      hippocampus. Recent studies have demonstrated that ependymal cells lining the
      central cord canal possess dormant neural stem cells capable of differentiation
      following Spinal Cord Injury (SCI). Recent research has focused on strategies to
      modulate cellular proliferation and differentiation in the spinal cord. In SCI
      these cells have the propensity to migrate to the site of damage and
      differentiate into astrocytes and oligodendrocytes. Ependymal cells are also
      capable of migrating into the hypothalamus and undergo proliferation.
      Neurological insult such as SCI leads the oxidative stress response, inflammation
      and subsequent activation of ependymal cells into astrocytes that are the body?s
      way to regenerate and heal. The presence or absence of astrocytes, neuronal
      growth factors, non-neuronal growth factors, microtubule and microtubule
      activating proteins are factors which promote cell survival and terminal
      differentiation of neurons. 

PMID- 25996734
TI  - Implementation of a Smart Phone for Motion Analysis.
AB  - In today?s information-rich environment, one of the most popular devices is a
      smartphone. Research has shown significant growth in the use of smartphones and
      apps all over the world. Accelerometer within smartphone is a motion sensor that
      can be used to detect human movements. Compared to other major vital signs, gait
      characteristics represent general health status, and can be determined using
      smartphones. The objective of the current study is to design and develop the
      alternative technology that can potentially predict health status and reduce
      healthcare cost. This study uses a smartphone as a wireless accelerometer for
      quantifying human motion characteristics from four steps of the system design and
      development (data acquisition operation, feature extraction algorithm, classifier
      design, and decision making strategy). Findings indicate that it is possible to
      extract features from a smartphone?s accelerometer using a peak detection
      algorithm. Gait characteristics obtain from the peak detection algorithm include
      stride time, stance time, swing time and cadence. Applications and limitations of
      this study are also discussed. 

PMID- 25996735
TI  - Subcortical Region Segmentation using Fuzzy Based Augmented Lagrangian Multiphase
      Level Sets Method in Autistic MR Brain Images.
AB  - In this work, the subcortical regions of control and autistic MR brain are
      segmented from the skull stripped images using Fuzzy C-Means (FCM) based
      Augmented Lagrangian (AL) multiphase level set method. The FCM method is used as
      he intensity discriminator for the multiphase level set method. The AL function
      avoids the re-initialization procedure. The segmented subcortical regions are
      validated with the ground truth images using dice similarity index. The texture
      features such as energy and entropy are calculated from the extracted cortical
      and subcortical regions. The results show that the multiphase level set method is
      able to segment the subcortical regions such as corpus callosum, brain stem and
      cerebellum. The dice similarity index gives above 0.85 for controls and 0.8 for
      autistic subjects. The texture feature energy calculated from the cortical region
      is high in autistics compared to the control subjects and vice versa in the case
      of entropy. The energy calculated from the subcortical regions is high in
      controls and entropy is high in autism subjects. Comparatively, the energyand
      entropy calculated from the total brain and brain stem gives significant
      variation (p<0.0001) between the control and autistic images. As the delayed
      growth of subcortical region is associated with high values of entropy, this
      study is clinically significant in the mass screening of neurodevelopmental
      disorders such as autism. 

PMID- 25996736
TI  - Study of Alzheimer?s Disease Progression In MR Brain Images based on Segmentation
      and Analysis of Ventricles using Modified DRLSE Method and Minkowski Functionals.
AB  - In this work, the ventricles in MR brain images are segmented using edge based
      modified Distance Regularized Level Set Evolution (DRLSE) method and the
      structural changes in the disease is further analysed using Minkowski functionals
      (MFs). Twenty normal and abnormal T1-weighted coronal mid slice MR image are
      considered for the analysis. The MR brain image is pre-processed using contrast
      enhancement method. The edge based modified DRLSE with a new penalty term is used
      to segment the ventricles from the enhanced images. The results of the level set
      method are compared with geodesic active contour method. The segmentation results
      are validated using ZSI (Zijdenbos Similarity Index) and F-score. The Minkowski
      functionals such as MF-area, MF-perimeter and MF-Euler number are calculated from
      the extracted ventricle region. The longitudinal analysis of ventricles is
      performed using these features. The results show that the DRLSE based level set
      method is able to extract the ventricle edges with less discontinuity. The F
      score and ZSI is high for DRLSE (0.83 and 0.84) compared to geodesic method (0.79
      and 0.80). The MF-area is able to discriminate the controls and the AD subjects
      with high statistical significance (p < 0.001). This analysis also shows that the
      MF- area increases with severity. These results could be used for the study of
      discrimination and progression of the Alzheimer's disease like disorders. 

PMID- 25996737
TI  - Robust Anisotropic Diffusion Based Edge Enhancement for Level Set Segmentation
      and Asymmetry Analysis of Breast Thermograms using Zernike Moments.
AB  - Breast thermography plays a major role in early detection of breast cancer in
      which the thermal variations are associated with precancerous state of breast.
      The distribution of asymmetrical thermal patterns indicates the pathological
      condition in breast thermal images. In this work, asymmetry analysis of breast
      thermal images is carried out using level set segmentation and Zernike moments.
      The breast tissues are subjected to Tukey?s biweight robust anisotropic diffusion
      filtering (TBRAD) for the generation of edge map. Reaction diffusion level set
      method is employed for segmentation in which TBRAD edge map is used as stopping
      criterion during the level set evolution. Zernike moments are extracted from the
      segmented breast tissues to perform asymmetry analysis. Results show that the
      TBRAD filter is able to enhance the edges near infra mammary folds and lower
      breast boundaries effectively. It is observed that segmented breast tissues are
      found to be continuous and has sharper boundary. This method yields high degree
      of correlation (98%) between the segmented output and the ground truth images.
      Among the extracted Zernike features, higher order moments are found to be
      significant in demarcating normal and carcinoma breast tissues by 9%. It appears
      that, the methodology adopted here is useful in accurate segmentation and
      differentiation of normal and carcinoma breast tissues for automated diagnosis of
      breast abnormalities. 

PMID- 25996738
TI  - An Approach to Diagnosis of Auto-Immune Diseases using HEP-2 Staining Pattern and
      Fractal Texture Features.
AB  - Observing and classifying the indirect immunofluorescence patterns on HEp-2 cells
      can help in detecting Anti-Nuclear-Antibodies. A computer algorithm to perform
      this function can lead to a more standardized, faster and accurate diagnosis of
      auto-immune diseases such as systemic lupus erythematosus, sjogren?s syndrome,
      and rheumatoid arthritis. In this paper, HEp-2 staining patterns are classified
      using segmentation based fractal texture features. The images used for this
      experimentation are obtained from a publicly available database. The features
      extracted from a cell image is used to classify it into homogenous, fine
      speckled, coarse speckled, centromere and nucleolus. The cell images are
      segmented using the ground truth mask provided in the database. Adaptive
      histogram equalization is applied to the segmented images for contrast
      enhancement. Three features namely mean intensity, area and Hausdorff fractal
      dimension of the border are extracted for 8 different Otsu threshold levels.
      Finally, the 24 features thus extracted are fed to a support vector machine with
      Gaussian radial basis function kernel. It is observed that the overall accuracy
      of classification is 65.17%. The accuracy is greatly dependent on scaling and
      distribution of the features given to SVM. It appears that the segmentation based
      fractal texture features and SVM could help to build a robust automated diagnosis
      tool for auto-immune diseases. 

PMID- 25996739
TI  - Segmentation and Analysis of Corpus Callosum in Alzheimer MR Images using Total
      Variation Based Diffusion Filter and Level Set Method.
AB  - Alzheimer?s Disease (AD) is a common form of dementia that affects gray and white
      matter structures of brain. Manifestation of AD leads to cognitive deficits such
      as memory impairment problems, ability to think and difficulties in performing
      day to day activities. Although the etiology of this disease is unclear, imaging
      biomarkers are highly useful in the early diagnosis of AD. Magnetic resonance
      imaging is an indispensible non-invasive imaging modality that reflects both the
      geometry and pathology of the brain. Corpus Callosum (CC) is the largest white
      matter structure as well as the main inter-hemispheric fiber connection that
      undergoes regional alterations due to AD. Therefore, segmentation and feature
      extraction are predominantly essential to characterize the CC atrophy. In this
      work, an attempt has been made to segment CC using edge based level set method.
      Prior to segmentation, the images are pre-processed using Total Variation (TV)
      based diffusion filtering to enhance the edge information. Shape based geometric
      features are extracted from the segmented CC images to analyze the CC atrophy.
      Results show that the edge based level set method is able to segment CC in both
      the normal and AD images. TV based diffusion filtering has performed uniform
      region specific smoothing thereby preserving the texture and small scale details
      of the image. Consequently, the edge map of CC in both the normal and AD are
      apparently sharp and distinct with continuous boundaries. This facilitates the
      final contour to correctly segment CC from the nearby structures. The extracted
      geometric features such as area, perimeter and minor axis are found to have the
      percentage difference of 5.97%, 22.22% and 9.52% respectively in the demarcation
      of AD subjects. As callosal atrophy is significant in the diagnosis of AD, this
      study seems to be clinically useful. 

PMID- 25996740
TI  - Health Impact of Retinoic Acid (ATRA) on Ovalbumin-Sensitized F344 Rat Lung and
      Improvement of Tissue Pathology by Citral.
AB  - The health impact of retinoic acid (All Trans Retinoic Acid; ATRA) in the
      development of lung pathology and tissue remodeling has not been well established
      in the literature. Equally, the role of Citral (inhibitor of retinoid function)
      in the improvement of lung pathology has not been ascertained in vivo. Therefore,
      it is hypothesized that ATRA and Ovalbumin (Egg albumin; OVA) exposure will
      sensitize lung tissues leading to lung tissue pathology and that citrals (C1 and
      C2) will reverse or ameliorate the related pathological damage to lung tissues.
      The study used an IACUC approved between-subject in vivo randomized split plot
      factorial design (F344 rat model; N=35). Animals were sensitized to OVA and then
      exposed to six different treatments; negative control (-ve), ATRA, Citrals (C1
      and C2) and their triple combinations (OVA+ ATRA + C1, OVA+ ATRA + C2), by intra
      peritoneal route. Rat weight data and blood were collected on Days 1 and 21, all
      animals were sacrificed on day 21, and lung tissues were processed for
      histopathology. Results from rat weights and blood (ANOVA and Duncan) as well as
      from the histopathological analysis of exposing the F344 rats to OVA in
      combinations with ATRA and citrals, revealed various levels of lung tissue damage
      that was impacted by exposure to citral. We conclude that OVA+ATRA+C1 combination
      treatment did improve lung pathology as compared to single individual treatments.
      However, the OVA+ATRA+C2 combination not only failed to improve these parameters,
      but even worsened the lung pathology of this model. This promising study showed
      variable responses on the interaction of Ovalbumin, citrals, and ATRA as related
      to their damage/improvement of related lung tissue pathologies. 

PMID- 25996742
TI  - Inexpensive Complex Hand Model Twenty Years Later.
AB  - Twenty years ago the author unveiled his inexpensive complex hand model, which
      reproduced every motion of the human hand. A control system programmed in the
      Forth language operated its actuators and sensors. Follow-on papers for this
      popular project were next presented in Texas, Canada and Germany. From this hand
      grew the author?s meter-tall robot (nicknamed ANNIE: Android With Neural
      Networks, Intellect and Emotions). It received machine vision, facial
      expressiveness, speech synthesis and speech recognition; a simian version also
      received a dexterous ape foot. New artificial intelligence features included op
      amp neurons for OCR and simulated emotions, hormone emulation, endocannabinoid
      receptors, fear-trust-love mechanisms, a Grandmother Cell recognizer and
      artificial consciousness. Simulated illnesses included narcotic addiction,
      autism, PTSD, fibromyalgia and Alzheimer?s disease. The author gave 13 robotics
      AI presentations at NASA in Houston since 2006. A meter-tall simian robot was
      proposed with gripping hand-feet for use with space vehicles and to explore
      distant planets and moons. Also proposed were: intelligent motorized exoskeletons
      for astronaut force multiplication; a cognitive prosthesis to detect and
      alleviate decreased crew mental performance; and a gynoid robot medic to tend
      astronauts in deep space missions. What began as a complex hand model evolved
      into an innovative robot-AI within two decades. 

PMID- 25996741
TI  - The Negative Impact of Combining Retinoic Acid (ATRA) and Mold Spores on F344 Rat
      Lung and Improvement of Tissue Pathology by Citral.
AB  - The impact of retinoic acid (All Trans Retinoic Acid; ATRA) and Mold spores (MLD)
      in the development of lung pathology and in vivo tissue remodeling have not been
      well established in the literature. In addition, the role of citral (inhibitor of
      retinoid function) in the improvement of lung pathology has not been ascertained
      in animal studies. Therefore, it is hypothesized that ATRA and Mold (MLD)
      exposure will sensitize lung tissues leading to lung tissue pathology and that
      Citrals (C1 and C2) will reverse, ameliorate or improve the associated
      pathological damage to lung tissues. The study used an IACUC approved between
      subject in vivo randomized split plot factorial design (F344 rat model; N=40).
      Animals were exposed to eight different treatments including vehicle, MLD, ATRA,
      Citrals (C1 and C2) and their MLD combinations (MLD+ ATRA, MLD+ C1, and MLD+ C2)
      by intra-peritoneal route. Rat weight and blood data were collected on Days 1 and
      21, all animals were sacrificed on day 21, and lung tissues were processed for
      histopathology. Results from weight and blood data (ANOVA and Duncan) as well as
      from histopathological analyses supported the findings that exposure of F344 rats
      to MLD combinations with ATRA and Citrals showed various levels of lung tissue
      damage that were impacted by either C1 or C2. This promising study showed
      impressive responses on the interaction of MLD, Citrals, and ATRA as related to
      their impact on associated lung tissue pathologies. 

PMID- 25996743
TI  - Predicting Targets of Human Reaching Motions With an Arm Rehabilitation
      Exoskeleton.
AB  - Rehabilitation robots physically support patients during exercise, but their
      assistive strategies often constrain patients by forcing them to execute
      predefined motions. To allow more freedom during rehabilitation, the robot should
      be able to predict what motion the patient wants to perform, then intelligently
      support the motion. As a first step, this paper presents an algorithm that
      predicts targets of reaching motions made with an arm rehabilitation exoskeleton.
      Different sensing modalities are compared with regard to their predictive
      abilities: arm kinematics, eye tracking, contextual information, and combinations
      of these modalities. Supervised machine learning is used to make predictions at
      different points of time during the motion. Results of offline crossvalidation
      using 12 healthy subjects show that eye tracking can make target predictions
      earlier and more accurately than arm kinematics, especially when possible targets
      are close together. Combining eye tracking with contextual information further
      improves prediction accuracy. The foreseen next step is to use our predictions to
      guide the rehabilitation robot, and then test the algorithm in real-time with
      stroke patients. 

PMID- 25996744
TI  - The Effects of Metformin and EGCG On PANC-1 Cell Survival.
AB  - There is less than a thirty percent survival rate for patients with a localized
      pancreatic tumor, and less than a ten percent survival rate for patients with
      metastases. Patients with pancreatic cancer often have altered glucose metabolism
      and are prescribed metformin which has been shown to reduce cancer cell
      proliferation. Metformin administered at doses ranging between 10-20 mM has been
      reported in the literature to induce AMPK signaling pathways which increase
      cellular apoptosis. Epigallacto-catechan (EGCG) is a polyphenolic antioxidant
      that has also been shown to increase the AMPK pathway that increases cellular
      apoptosis. The objective of this study was to investigate the effectiveness of
      EGCG with a clinical dose of metformin (10uM) in reducing the survival of a
      pancreatic like cell line in culture. PANC-1 cells were plated onto three 24 well
      plates at a density of 1 x 106 cells per well. The experimental design consisted
      of four equal groups: Group 1 served as the control and groups 2-4 were treated
      with metformin, (EGCG) or metformin and EGCG, respectively. Biochemical and
      morphological evaluations were conducted following standard lab protocols.
      Results of this study show 10uM of metformin was unable to alter cell growth or
      proliferation over a 72 hour period, while 50uM of EGCG alone or in combination
      with metformin were capable of reducing cell density and cellular protein levels
      at 48 and 72 hours following treatment. The results show EGCG induced changes in
      cellular morphology which are characteristic of apoptosis. Overall, additional
      studies are needed to determine the effects of EGCG on AMPK and ATM pathways that
      are responsible in normal cellular apoptotic processes. 

PMID- 25996745
TI  - The Effect Of Selective Serotonin Reuptake Inhibitors and Antidiabetic Drugs on
      Cardiomyocytes.
AB  - Recent reports in the literature show an increase in the risk of heart related
      events in patients treated with tricyclic antidepressants. There is also evidence
      that serotonin reuptake inhibitors (SSRIs) are negatively associated with heart
      failure. The objective of our study is to determine if cardiomyocytes in culture
      can be used as a tool to mimic clinical scenarios and to evaluate therapeutic
      concentrations of SSRIs (fluoxetine) and antidiabetic (troglitazone) medication.
      Cardiomyocytes were grown in a tissue culture environment and challenged with
      therapeutic concentrations of SSRIs alone or a combination of SSRIs and
      antidiabetic drugs. Intracellular markers for stress and cytomorphometric
      analysis indicated SSRIs and SSRIs in combination with antidiabetic drugs
      negatively impact the health of the cardiomyocytes with time in culture. Analysis
      of the nuclear area and cytoplasmic changes are sensitive enough to use a cell
      based model for determination of adverse effects associated with co
      administration of drugs. 

PMID- 25996746
TI  - The Tissue Implant Response Surrounding Subcutaneous TCP, HA, And ALCAP
      Bioceramics.
AB  - The objective of this investigation was to quantify and further elucidate the
      tissue-implant response in the fibrous tissue surrounding tricalcium phosphate
      (TCP), hydroxyapatite (HA), and aluminum calcium phosphate (ALCAP) implants when
      implanted subcutaneously. Sixteen animals in four experimental groups (n =
      4/group) were implanted with one implant each: Group I (control, TCP), Group II
      (HA), and Group III (ALCAP). At 90 days post-implantation, the fibrous tissue
      surrounding the implants was harvested. Sections of stained fibrous tissue were
      evaluated for the presence of macrophages, fibrocytes, neutrophils, vascularity
      and thickness for all three groups using semi-automated quantitative methods. The
      analysis indicated Group III demonstrated a significantly higher number of
      neutrophils but fewer macrophages and blood vessels per high power field and had
      a substantially thinner fibrous tissue capsule thickness compared to Groups I and
      II (alpha=0.05). Group II elicited a greater response of fibroblasts compared to
      Groups I and III suggesting HA may provide a slightly higher degree of stability
      to the implant. In total, these findings suggest both TCP and HA behave similarly
      in vivo when compared to ALCAP and may be better choices for subcutaneous soft
      tissue application compared to ALCAP. 

PMID- 25996747
TI  - Neovascularization And Macrophage Behavior Under The Influence Of Androgens In
      The Tissue-Implant Response.
AB  - Macrophages and blood vessels are critical components in the biocompatibility and
      functionality of implantable ceramic materials used in drug delivery
      applications. The purpose of this study was to examine the correlation of
      macrophage and neovascularization by further defining their presence,
      relationship, and correlation in the fibrous tissue capsule of calcium phosphate
      (TCP) ceramic drug delivery systems. Sixteen animals in four experimental groups
      were implanted with one TCP bioceramic each. Group I animals were implanted with
      a TCP ceramic not containing a biologic (control group). Group II animals
      received the testosterone loaded TCP ceramic. Group III animals were implanted
      with the dihydrotestosterone loaded ceramic. Group IV animals received the
      androstenedione ceramic. At 90 days post-implantation, the animals were
      euthanized. Implants and fibrous tissue capsules were collected. Determination of
      macrophage populations and neovascularity was conducted microscopically following
      H&E staining and aided by ImagePro digital analysis software. Androgens have
      varying effects on vascularity and macrophage populations. Overall, macrophage
      counts were highly and significantly correlated with vascularity (p<0.05),
      particularly in Groups II, III, and IV. Correlations for Group I was not
      statistically significant. These findings suggest that presence of macrophages is
      be directly related to neovascularity, especially in the presence of exogenous
      androgens. 

PMID- 25996748
TI  - Blast Induced Neurotrauma Leads To Changes In The Epigenome.
AB  - Blast induced neurotrauma (BINT) leads to widespread aberrant gene expression and
      molecular changes resulting in cognitive impairment. Enzymes such as HDAC2,
      HDAC6, SIRT1, DNMT1, DNMT3a and DNMT3b control histone acetylation and DNA
      methylation which play a major role in regulation of the transcriptome. Changes
      in the expression of these enzymes have been implicated in the pathology of
      traumatic brain injury (TBI) and Alzheimer?s disease (AD). We hypothesize that
      blast exposure will lead to changes in the expression of these enzymes which play
      a key role in injury progression and pathology. This study looked to identify
      epigenome changes in the acute stages of BINT using an established rodent model.
      Real time polymerase chain reaction and Western blot analyses were used to assess
      gene expression and protein level changes compared to sham. No significant
      changes were seen 24 hours after blast exposure. However, several changes were
      observed at 72 hours following blast exposure. There was a significant increase
      in expression of HDAC2 and HDAC6 in the hippocampus which correlated with
      elevated HDAC2 protein levels. SIRT1, DNMT3a and DNMT3b levels were all reduced
      in the hippocampus. In the medial prefrontal cortex, DNMT1 and DNMT3b were
      significantly reduced. The results indicated that blast exposure causes acute
      changes in gene expression and protein levels of epigenetic markers which
      correlate with changes observed in AD pathology. These epigenomic changes could
      provide novel targets for therapeutic interventions following BINT. 

PMID- 25996749
TI  - Injuries to Post Mortem Human Surrogates in Oblique Aircraft Seat Environment.
AB  - Increased interest in the airline industry to enhance occupant comfort and
      maximize seating density has prompted the design and installation of obliquely
      mounted seats in aircraft. The potential for injury and their mechanism in this
      seating environment is unknown. Epidemiology-based field injury data do not exist
      for airplane crashes, however, typical impact scenarios have been determined and
      safety standards addressing fore, aft, and side-facing seats have been levied by
      the FAA. The impact scenarios defined in these standards can be used to study
      likely injuries and injury mechanisms using Post Mortem Human Surrogates (PMHS)
      in a controlled laboratory environment. Four PMHS were seated upright with
      Frankfurt plane horizontal in a custom designed seat configured to simulate
      potential aircraft environments and candidate restraint geometries. A scaled Part
      25.562 Emergency Landing condition for horizontal impact was used as the dynamic
      test input. High speed video recorded occupant kinematics. Pre and posttest x
      rays and CT?s were obtained and autopsies were conducted. Severe injuries to the
      cervical, thoracic, and lumbar spine were observed in three of the four specimens
      and attributed to torso flail. Pelvis injuries likely caused by the seat belt
      were found in two tests. Multiple rib fractures were also seen, caused by contact
      with arm rest or other body regions. The fourth test was run at a lower severity
      and did not produce injury. This suggests a conservative threshold for human
      tolerance to this loading environment. Although the study is of a limited sample
      size, it suggests the need for further testing to develop standards that provide
      similar levels of safety for obliquely mounted seats as forward/aft facing seats
      in aircraft. 

PMID- 25996750
TI  - Two and Three-Dimensional in Vitro Models of Blast-Induced Neurotrauma.
AB  - Blast-induced neurotrauma (BINT) has become an increasingly significant concern
      in Veterans returning from warfare. Associated brain injury and cognitive
      deficits are difficult to diagnose as the nature of this injury is progressive.
      In order to better understand the mechanisms of BINT at the microscopic level,
      two- and three-dimensional models of astrocytes were studied. The 3-D model was
      developed using Matrigel(r) to embed the cells. Injury was induced by exposure to
      an overpressure of 20 psi (140 kPa) using a shock wave generator which simulates
      a free field blast profile. Cellular viability was measured by MTT assays
      conducted at 24 and 48 hours post-blast. Gene expression levels of glial
      fibrillary acidic protein (GFAP), beta-actin, and vinculin were analyzed as
      potential structural biomarkers of injury at 48 and 72 hours post-blast. Results
      indicated that glial cells survived and became activated by 72 hours following
      exposure. Specifically, gene expression of GFAP was elevated in simulated blast
      cultures as compared to controls. Moreover, 2- and 3-D cultures were observed to
      have different time periods of activation. These activation markers may be useful
      when designing therapeutic targets to mitigate injury progression. 

PMID- 25996751
TI  - Impact of electrode configurations on retention time and domestic wastewater
      treatment efficiency using microbial fuel cells.
AB  - Efficient treatment of domestic wastewater under continuous flow conditions using
      microbial fuel cells (MFCs) requires hydraulic retention times (HRTs) that are
      similar to or less than those of conventional methods such as activated sludge.
      Two MFCs in series were compared at theoretical HRTs of 8.8, 4.4 and 2.2 h using
      two different brush-electrode MFC configurations: a full brush evenly spaced
      between two cathodes (S2C); and trimmed brush anodes near a single cathode (N1C).
      The MFCs with two cathodes produced more power than the MFCs with a single
      cathode, with 1.72 mW for the S2C, compared to and 1.12 mW for the N1C at a set
      HRT = 4.4 h. The single cathode MFCs with less cathode area removed slightly more
      COD (54.2 +/- 2.3%, N1C) than the two-cathode MFCs (48.3 +/- 1.0%, S2C). However,
      the higher COD removal was due to the longer HRTs measured for the MFCs with the
      N1C configuration (10.7, 5.3 and 3.1 h) than with the S2C configuration (7.2, 3.7
      and 2.2 h), despite the same theoretical HRT. The longer HRTs of the N1C MFCs
      also resulted in slightly higher coulombic efficiencies (<=37%) than those of the
      S2C MFCs (<=29%). While the S2C MFC configuration would be more advantageous
      based on electrical power production, the N1C MFC might be more useful on the
      basis of capital costs relative to COD removal efficiency due to the use of less
      cathode surface area per volume of reactor.

PMID- 25996752
TI  - Network hydraulics inclusion in water quality event detection using multiple
      sensor stations data.
AB  - Event detection is one of the current most challenging topics in water
      distribution systems analysis: how regular on-line hydraulic (e.g., pressure,
      flow) and water quality (e.g., pH, residual chlorine, turbidity) measurements at
      different network locations can be efficiently utilized to detect water quality
      contamination events. This study describes an integrated event detection model
      which combines multiple sensor stations data with network hydraulics. To date
      event detection modelling is likely limited to single sensor station location and
      dataset. Single sensor station models are detached from network hydraulics
      insights and as a result might be significantly exposed to false positive alarms.
      This work is aimed at decreasing this limitation through integrating local and
      spatial hydraulic data understanding into an event detection model. The spatial
      analysis complements the local event detection effort through discovering events
      with lower signatures by exploring the sensors mutual hydraulic influences. The
      unique contribution of this study is in incorporating hydraulic simulation
      information into the overall event detection process of spatially distributed
      sensors. The methodology is demonstrated on two example applications using base
      runs and sensitivity analyses. Results show a clear advantage of the suggested
      model over single-sensor event detection schemes. 

PMID- 25996753
TI  - Increasing RO efficiency by chemical-free ion-exchange and Donnan dialysis:
      Principles and practical implications.
AB  - Ion-exchange (IEX) and Donnan dialysis (DD) are techniques which can selectively
      remove cations, limiting scaling in reverse osmosis (RO). If the RO concentrate
      could be recycled for regeneration of these pre-treatment techniques, RO recovery
      could be largely increased without the need for chemical addition or additional
      technologies. In this study, two different RO feed streams (treated industrial
      waste water and simple tap water) were tested in the envisioned IEX-RO and DD-RO
      hybrids including RO concentrate recycling. The efficiency of multivalent cation
      removal depends mainly on the ratio of monovalent to multivalent cations in the
      feed stream, influencing the ion-exchange efficiency in both IEX and DD. Since
      the mono-to-multivalent ratio was very high in the waste water, the RO recovery
      could potentially be increased to 92%. For the tap water, these high RO
      recoveries could only be reached by adding additional NaCl, because of the low
      initial monovalent to multivalent ratio in the feed. In both cases, the IEX-RO
      hybrid proved to be most cost-efficient, due to the high current cost of the
      membranes used in DD. The membrane cost would have to decrease from +/-300 ?/m2
      to 10-30 ?/m2 - comparable to current reverse osmosis membranes - to achieve a
      comparable cost. In conclusion, the recycling of RO concentrate to regenerate ion
      exchange pre-treatment techniques for RO is an interesting option to increase RO
      recovery without addition of chemicals, but only at high monovalent/multivalent
      cation-ratios in the feed stream. 

PMID- 25996754
TI  - The precipitation of magnesium potassium phosphate hexahydrate for P and K
      recovery from synthetic urine.
AB  - Nutrients recovery from urine to close the nutrient loop is one of the most
      attractive benefits of source separation in wastewater management. The current
      study presents an investigation of the thermodynamic modeling of the recovery of
      P and K from synthetic urine via the precipitation of magnesium potassium
      phosphate hexahydrate (MPP). Experimental results show that maximum recovery
      efficiencies of P and K reached 99% and 33%, respectively, when the precipitation
      process was initiated only through adding dissolvable Mg compound source. pH
      level and molar ratio of Mg:P were key factors determining the nutrient recovery
      efficiencies. Precipitation equilibrium of MPP and magnesium sodium phosphate
      heptahydrate (MSP) was confirmed via precipitates analysis using a Scanning
      Electron Microscope/Energy Dispersive Spectrometer and an X-ray Diffractometer.
      Then, the standard solubility products of MPP and MSP in the synthetic urine were
      estimated to be 10(-12.2 +/- 0.0.253) and 10(-11.6 +/- 0.253), respectively. The
      thermodynamic model formulated on chemical software PHREEQC could well fit the
      experimental results via comparing the simulated and measured concentrations of K
      and P in equilibrium. Precipitation potentials of three struvite-type compounds
      were calculated through thermodynamic modeling. Magnesium ammonium phosphate
      hexahydrate (MAP) has a much higher tendency to precipitate than MPP and MSP in
      normal urine while MSP was the main inhibitor of MPP in ammonium-removed urine.
      To optimize the K recovery, ammonium should be removed prior as much as possible
      and an alternative alkaline compound should be explored for pH adjustment rather
      than NaOH. 

PMID- 25996755
TI  - Moving towards sustainable resources: Recovery and fractionation of nutrients
      from dairy manure digestate using membranes.
AB  - The fractionation of nitrogen (as ammonia/ammonium) and phosphorus (as phosphate
      ions) present in the dairy manure digestate was investigated using a
      nanofiltration membrane NF270. The filtration and separation efficiencies were
      correlated to pH across the range 3 < pH < 11. Filtration at pH 11 enabled higher
      permeate flux of 125-150 LMH at 20 bar, however rejection of ammonia was high at
      30-36% and phosphate was 96.4-97.2%. At pH 3 and pH 7, electrostatic charge
      effects led to higher permeation of ammonium and thus more efficient separation
      of nitrogen. The rejection of phosphorus was relatively constant at any given pH
      and determined as 83% at pH 3, 97% at pH 7 and 95% at pH 11. The fractionation of
      nitrogen and phosphorus from complex aqueous solutions was demonstrated to be
      highly dependent on the charge of the membrane and ionic speciation. Solutions
      rich in nitrogen (as ammonia/ammonium) were obtained with almost no phosphorus
      present (<1 ppm) whilst the purification of the PO4-P was achieved by series of
      diafiltration (DF) operations which further separated the nitrogen. The
      separation of nutrients benefited from an advantageous membrane process with
      potential added value for a wide range of industries. The analysis of the process
      economics for a membrane based plant illustrates that the recovery of nutrients,
      particularly NH3-N, may be commercially feasible when compared to manufactured
      anhydrous NH3.

PMID- 25996756
TI  - Determination of the external mass transfer coefficient and influence of mixing
      intensity in moving bed biofilm reactors for wastewater treatment.
AB  - In moving bed biofilm reactors (MBBR), the removal of pollutants from wastewater
      is due to the substrate consumption by bacteria attached on suspended carriers.
      As a biofilm process, the substrates are transported from the bulk phase to the
      biofilm passing through a mass transfer resistance layer. This study proposes a
      methodology to determine the external mass transfer coefficient and identify the
      influence of the mixing intensity on the conversion process in-situ in MBBR
      systems. The method allows the determination of the external mass transfer
      coefficient in the reactor, which is a major advantage when compared to the
      previous methods that require mimicking hydrodynamics of the reactor in a flow
      chamber or in a separate vessel. The proposed methodology was evaluated in an
      aerobic lab-scale system operating with COD removal and nitrification. The impact
      of the mixing intensity on the conversion rates for ammonium and COD was tested
      individually. When comparing the effect of mixing intensity on the removal rates
      of COD and ammonium, a higher apparent external mass transfer resistance was
      found for ammonium. For the used aeration intensities, the external mass transfer
      coefficient for ammonium oxidation was ranging from 0.68 to 13.50 m d(-1) and for
      COD removal 2.9 to 22.4 m d(-1). The lower coefficient range for ammonium
      oxidation is likely related to the location of nitrifiers deeper in the biofilm.
      The measurement of external mass transfer rates in MBBR will help in better
      design and evaluation of MBBR system-based technologies.

PMID- 25996757
TI  - Simulation and comparative study on the oxidation kinetics of atrazine by
      UV/H2O2, UV/HSO5- and UV/S2O82-.
AB  - This study comparatively investigated atrazine (ATZ) degradation by irradiation
      at the wavelength of 254 nm in the presence of peroxides including hydrogen
      peroxide (H2O2), peroxymonosulfate (HSO5(-)), and persulfate (S2O8(2-)) at
      various initial ATZ concentrations and oxidant dosages. The effects of water
      matrix, such as carbonate/bicarbonate (HCO3(-)/CO3(2-)), chloride ions (Cl(-)),
      and natural organic matter (NOM), were evaluated on these three advanced
      oxidation processes. A simple steady-state kinetic model was developed based on
      the initial rates of ATZ destruction, which could well describe the apparent
      pseudo-first-order rate constants (k(app), s(-1)) of ATZ degradation in these
      three processes. The specific roles of reactive species (i.e., HO., SO4(-.), CO3(
      .), and Cl2(-.)) under various experimental conditions were quantitatively
      evaluated based on their steady-state concentrations obtained from this model.
      Modeling results showed that the steady-state concentrations of HO. and SO4(-.)
      decreased with the increase of CO3(2-)/HCO3(-) concentration, and the relative
      contribution of HO. to ATZ degradation significantly decreased in UV/H2O2 and
      UV/HSO5(-) systems. On the other hand, the scavenging effect of HCO3(-)/CO3(2-)
      on the relative contribution of SO4(-.) to ATZ degradation was lower than that on
      HO.. The presence of Cl(-) (0.5-10 mM) significantly scavenged SO4(-.) but had
      slightly scavenging effect on HO. at the present experimental pH, resulting in
      greater decrease of k(app) in the UV/S2O8(2-) than UV/H2O2 and UV/HSO5(-)
      systems. Higher levels of Cl2(-.) were generated in the UV/S2O8(2-) than those in
      the UV/H2O2 and UV/HSO5(-) systems at the same Cl(-) concentrations. NOM
      significantly decreased k(app) due to its effects of competitive UV absorption
      and radical scavenging with the latter one being dominant. These results improve
      the understanding of the effects of water constituents for ATZ degradation in the
      UV-based oxidation processes.

PMID- 25996758
TI  - A multivariate based event detection method and performance comparison with two
      baseline methods.
AB  - Early warning systems have been widely deployed to protect water systems from
      accidental and intentional contamination events. Conventional detection
      algorithms are often criticized for having high false positive rates and low true
      positive rates. This mainly stems from the inability of these methods to
      determine whether variation in sensor measurements is caused by equipment noise
      or the presence of contamination. This paper presents a new detection method that
      identifies the existence of contamination by comparing Euclidean distances of
      correlation indicators, which are derived from the correlation coefficients of
      multiple water quality sensors. The performance of the proposed method was
      evaluated using data from a contaminant injection experiment and compared with
      two baseline detection methods. The results show that the proposed method can
      differentiate between fluctuations caused by equipment noise and those due to the
      presence of contamination. It yielded higher possibility of detection and a lower
      false alarm rate than the two baseline methods. With optimized parameter values,
      the proposed method can correctly detect 95% of all contamination events with a
      2% false alarm rate. 

PMID- 25996759
TI  - Groundwater ecosystem resilience to organic contaminations: microbial and
      geochemical dynamics throughout the 5-year life cycle of a surrogate ethanol
      blend fuel plume.
AB  - The capacity of groundwater ecosystem to recover from contamination by organic
      chemicals is a vital concern for environmental scientists. A pilot-scale aquifer
      system was used to investigate the long-term dynamics of contaminants,
      groundwater geochemistry, and microbial community structure (by 16S rRNA gene
      pyrosequencing and quantitative real-time PCR) throughout the 5-year life cycle
      of a surrogate ethanol blend fuel plume (10% ethanol + 50 mg/L benzene + 50 mg/L
      toluene). Two-year continuous ethanol-blended release significantly changed the
      groundwater geochemistry (resulted in anaerobic, low pH, and organotrophic
      conditions) and increased bacterial and archaeal populations by 82- and 314-fold
      respectively. Various anaerobic heterotrophs (fermenters, acetogens, methanogens,
      and hydrocarbon degraders) were enriched. Two years after the release was shut
      off, all contaminants and their degradation byproducts disappeared and
      groundwater geochemistry completely restored to the pre-release states (aerobic,
      neutral pH, and oligotrophic). Bacterial and archaeal populations declined by 18-
      and 45-fold respectively (relative to the time of shut off). Microbial community
      structure reverted towards the pre-release states and alpha diversity indices
      rebounded, suggesting the resilience of microbial community to ethanol blend
      releases. We also found shifts from O2-sensitive methanogens (e.g.,
      Methanobacterium) to methanogens that are not so sensitive to O2 (e.g.,
      Methanosarcina and Methanocella), which is likely to contribute to the
      persistence of methanogens and methane generation following the source removal.
      Overall, the rapid disappearance of contaminants and their metabolites, rebound
      of geochemical footprints, and resilience of microbial community unequivocally
      document the natural capacity of groundwater ecosystem to attenuate and recover
      from a large volume of catastrophic spill of ethanol-based biofuel.

PMID- 25996760
TI  - How Weight Affects the Perceived Spacing between the Thumb and Fingers during
      Grasping.
AB  - We know much about mechanisms determining the perceived size and weight of lifted
      objects, but little about how these properties of size and weight affect the body
      representation (e.g. grasp aperture of the hand). Without vision, subjects (n =
      16) estimated spacing between fingers and thumb (perceived grasp aperture) while
      lifting canisters of the same width (6.6cm) but varied weights (300, 600, 900,
      and 1200 g). Lifts were performed by movement of either the wrist, elbow or
      shoulder to examine whether lifting with different muscle groups affects the
      judgement of grasp aperture. Results for perceived grasp aperture were compared
      with changes in perceived weight of objects of different sizes (5.2, 6.6, and 10
      cm) but the same weight (600 g). When canisters of the same width but different
      weights were lifted, perceived grasp aperture decreased 4.8% [2.2 - 7.4] (mean
      [95% CI]; P < 0.001) from the lightest to the heaviest canister, no matter how
      they were lifted. For objects of the same weight but different widths, perceived
      weight decreased 42.3% [38.2 - 46.4] from narrowest to widest (P < 0.001), as
      expected from the size-weight illusion. Thus, despite a highly distorted
      perception of the weight of objects based on their size, we conclude that
      proprioceptive afferents maintain a reasonably stable perception of the aperture
      of the grasping hand over a wide range of object weights. Given the small
      magnitude of this 'weight-grasp aperture' illusion, we propose the brain has
      access to a relatively stable 'perceptual ruler' to aid the manipulation of
      different objects. 

PMID- 25996761
TI  - Synergistically Enhanced Therapeutic Effect of a Carrier-Free HCPT/DOX Nanodrug
      on Breast Cancer Cells through Improved Cellular Drug Accumulation.
AB  - We are interested in developing systems for simultaneous delivery of two or more
      chemotherapeutic agents. Simple physical mixing of drugs may reduce the
      therapeutic effect and cause unexpected or even dangerous side-effects. For
      example, when 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) injection
      solutions are mixed, the curative effect is actually reduced in clinical
      practice. In this study we demonstrated that when HCPT and DOX are combined into
      a single nanoparticle, their toxicity to tumor cells in vitro is synergistically
      enhanced. We used a simple and "green" reprecipitation method to successfully
      create a carrier-free dual-drug delivery system by self-nanocrystallization of
      the drug molecules. When HCPT and DOX were coassembled, they formed small,
      spherical nanodrug particles with a positive surface charge. Cellular uptake of
      HCPT was improved and nuclear accumulation increased as much as 1.57-fold in
      comparison to HCPT alone. The carrier-free HCPT/DOX nanoparticles demonstrated
      enhanced synergistic cytotoxicity against breast cancer cells in vitro, while an
      antagonistic effect was observed when HCPT and DOX were directly mixed at high
      concentration. 

PMID- 25996762
TI  - Efficacy of an intrathecal multidrug infusion for pain control in older adults
      and in end-stage malignancies: A report of three cases.
AB  - The aim of the present study was to explore the effectiveness of an alternative
      method to manage pain based on a time-limited intrathecal (IT) infusion of an
      analgesic medication mixture. Three patients (69, 64 and 94 years of age) with
      intractable and poorly controlled pain due to bed sores, pelvic metastatic mass,
      and thoracic vertebra and rib fractures, respectively, were treated. Daily doses
      of opioids could not be increased due to side effects. An IT catheter (20 G) was
      placed by percutaneous approach in the lumbar area while advancing toward the
      thoracic region, and was then tunnelled and fixed subcutaneously. It was
      connected to an external infusion pump with a mixture of bupivacaine 1 mg/mL,
      naloxone 0.02 ng/mL, ketamine 100 ug/mL, morphine 0.01 mg/mL and clonidine 0.75
      ug/mL. The starting rate was 1 mL/h. The pain was mostly controlled at a rate of
      <1 mL/h. Opioid consumption was reduced dramatically. The catheter was kept in
      place for one month in the first and third patients, and for six months in the
      second patient, until his death. Major side effects, such as hypotension,
      constipation, muscle weakness, sphincter dysfunction, and cognitive or mood
      deterioration, were not observed with this approach. One patient experienced a
      urinary tract infection followed by sepsis and meningitis, which was cured by
      antibiotics. The catheter was removed in this patient. IT infusion with a low
      concentration multidrug mixture could be considered as an alternative modality
      for intractable pain relief in older adults or in malignancies. 

PMID- 25996763
TI  - Do photographic images of pain improve communication during pain consultations?
AB  - BACKGROUND: Visual images may facilitate the communication of pain during
      consultations. OBJECTIVES: To assess whether photographic images of pain enrich
      the content and/or process of pain consultation by comparing patients' and
      clinicians' ratings of the consultation experience. METHODS: Photographic images
      of pain previously co-created by patients with a photographer were provided to
      new patients attending pain clinic consultations. Seventeen patients selected and
      used images that best expressed their pain and were compared with 21 patients who
      were not shown images. Ten clinicians conducted assessments in each condition.
      After consultation, patients and clinicians completed ratings of aspects of
      communication and, when images were used, how they influenced the consultation.
      RESULTS: The majority of both patients and clinicians reported that images
      enhanced the consultation. Ratings of communication were generally high, with no
      differences between those with and without images (with the exception of
      confidence in treatment plan, which was rated more highly in the image group).
      However, patients' and clinicians' ratings of communication were inversely
      related only in consultations with images. Methodological shortcomings may
      underlie the present findings of no difference. It is also possible that using
      images raised patients' and clinicians' expectations and encouraged emotional
      disclosure, in response to which clinicians were dissatisfied with their
      performance. CONCLUSIONS: Using images in clinical encounters did not have a
      negative impact on the consultation, nor did it improve communication or
      satisfaction. These findings will inform future analysis of behaviour in the
      video-recorded consultations.

PMID- 25996764
TI  - Is a single low dose of intrathecal morphine a useful adjunct to patient
      controlled analgesia for postoperative pain control following lumbar spine
      surgery? A preliminary report.
AB  - BACKGROUND: Several studies addressing intrathecal morphine (ITM) use following
      spine surgery have been published either involving the pediatric population,
      using mid- to high-dose ITM, or not in conjunction with morphine patient
      controlled analgesia (PCA). OBJECTIVES: To determine whether low-dose ITM is a
      useful adjunct to PCA for postoperative pain control following elective lumbar
      spine surgery in adults. METHODS: Thirty-two patients were enrolled in a double
      blinded randomized controlled trial, and received either ITM or intrathecal
      placebo. Postoperatively, all patients were given a PCA pump and observed for the
      first 24 h in a step-down unit. Measurements of: total PCA morphine consumed in
      the first 24 h; intensity of pain; pruritus; nausea at 4 h, 8 h and 24 h; time to
      first ambulation; length of hospital stay; and occurrences of respiratory
      depression were recorded. RESULTS: The total PCA use was significantly lower in
      the ITM group. There were lower average pain scores in the ITM group, which
      increased to that of the intrathecal placebo group over 24 h; however, this
      failed to attain statistical significance. There were no differences in nausea,
      pruritus, time to first ambulation or hospital length stay. There were no cases
      of respiratory depression in either group. CONCLUSIONS: ITM may be a useful
      adjunct to PCA, but did not decrease time to ambulation or length of stay.

PMID- 25996765
TI  - Assessment of pain and stress intensity among women with ovarian endometriomas
      versus teratomas.
AB  - BACKGROUND: In recent years, numerous studies have considered endometriosis to be
      a subclinical, local inflammatory process in the pelvic peritoneum, the main
      symptom of which is pain. OBJECTIVES: To assess pain intensity and pain-related
      stress in women with ovarian endometriomas versus teratomas. METHODS: In total,
      860 women (18 to 38 years of age) treated laparoscopically for lesions in the
      adnexa between September 2006 and November 2013 were included in the present
      study. After an intraoperative review of their histopathological lesions, the
      patients were divided into two study groups: group E (n=480), with
      histopathologically confirmed ovarian endometriomas; and group T (n=380), after
      laparoscopic treatment of ovarian teratomas. A questionnaire was generated for
      the study and completed by each group. Statistical analysis was performed using
      the Mann-Whitney U test (P<=0.05). RESULTS: Median pain scores for group E versus
      group T were as follows: pain during menstruation, 6 versus 3 (P=0.001); pain
      outside of menstruation (in professional life), 2 versus 2 (P=0.014); and pain
      during sexual intercourse, 3 versus 1 (P=0.006). Pain-related stress scores were
      higher in group T versus group E (5 versus 3; P=0.007). CONCLUSION: Ovarian
      endometriomas caused more pain than ovarian teratomas, likely due to the
      endometrial tissue component and not a mass effect. The assessment of pain and
      pain-related stress associated with the pelvis minor showed a high level of pain
      intensity and lower level of pain-related stress among patients with ovarian
      endometriomas.

PMID- 25996766
TI  - The relationship between fibromyalgia and pressure pain threshold in patients
      with dyspareunia.
AB  - OBJECTIVE: To evaluate the number of tender points, pressure pain threshold and
      presence of fibromyalgia among women with or without dyspareunia. METHODS: The
      present cross-sectional study included 40 patients with dyspareunia and 30
      healthy controls. The participants were asked if they had engaged in sexual
      intercourse during the previous four weeks, and dyspareunia was rated from 0 to 3
      based on the Marinoff Dyspareunia Scale. A pressure algometer (dolorimeter) was
      used to measure the pressure pain threshold. Fibromyalgia was diagnosed based on
      the 1990 American College of Rheumatology criteria. The depression status of the
      participants was assessed using the Beck Depression Inventory. RESULTS: No
      statistically significant difference was found with regard to age, body mass
      index, habits (alcohol use and smoking), educational status and occupational
      status between the two groups. Total myalgic score, total control score and
      tender point mean pain threshold were significantly lower in the group with
      dyspareunia. The number of tender points was significantly higher in patients
      with dyspareunia. The mean Beck Depression Inventory score was 14.7+/-8.4 in the
      dyspareunia group compared with 11.2+/-7.1 in the control group. Five (12.5%) of
      the patients with dyspareunia were diagnosed with fibromyalgia, whereas no
      patients in the control group were diagnosed with fibromyalgia. There was no
      significant difference between the two groups with regard to the presence of
      fibromyalgia. CONCLUSION: The finding of lower pressure pain thresholds and a
      higher number of tender points among patients with dyspareunia suggests that
      these patients may have increased generalized pain thresholds. Additional studies
      involving a larger number of patients are required to investigate the presence of
      central mechanisms in the pathogenesis of dyspareunia.

PMID- 25996767
TI  - Use of morphine sulphate by South African paramedics for prehospital pain
      management.
AB  - BACKGROUND: Evidence in the literature highlights the fact that acute pain in the
      prehospital setting remains poorly managed. Morphine remains the most commonly
      used analgesic agent in the South African prehospital emergency care setting.
      Although guidelines and protocols relating to the dosage and administration of
      morphine exist, little data are available describing its use by South African
      paramedics. OBJECTIVES: To document and describe the way in which morphine is
      administered by a sample of South African paramedics for the management of acute
      pain in the prehospital setting. METHODS: An Internet-based survey was conducted.
      Sixty South African paramedics responded by completing the online questionnaire
      documenting and describing their use of morphine for management of acute pain.
      RESULTS: Results revealed that participants appeared to be overly cautious of
      potential adverse effects associated with administration of morphine. Although
      the majority of participants calculated the dose of morphine to be administered
      correctly according to the patient's weight, the majority do not appear to be
      administering this as a bolus; rather, they administer the calculated loading
      dose in a titrated manner over time. This method may result in a delay and or
      failure to adequately achieve therapeutic serum levels. CONCLUSION: Failure to
      administer an appropriate bolus or 'loading dose' when administering morphine
      intravenously may result in ineffective and delayed pain management. The authors
      recommend more clearly defined protocols be developed to guide the use of
      morphine sulphate by paramedics in the local emergency medical services
      environment.

PMID- 25996768
TI  - Continuous assessment of labour pain using handgrip force.
AB  - BACKGROUND: Assessment of dynamic changes in painful experiences, such as labour,
      using conventional rating scales (eg, numerical rating scale [NRS]) has
      limitations. An alternative for continuous pain evaluation could be a signal
      generated by voluntary action of the parturient. Remifentanil administration for
      obstetric analgesia could be improved by these dynamic measures of labour pain.
      In the present study, handgrip force was measured by a dynamometer to signal
      labour pain. OBJECTIVES: To evaluate: whether continuous monitoring of labour
      pain using handgrip force allows for determination of pain measurement during
      contractions; and the correlation between handgrip force and pain intensity on
      NRS. METHODS: The present observational, single-centre study included 43
      parturients. After calibration of the dynamometer for individual hand muscle
      strength, pain was recorded during early and late labour using a dynamometer and
      an NRS. The primary end point was the correlation coefficient between NRS ratings
      and peak intensity recorded by the dynamometer. RESULTS: All dynamometer
      registered readings were also registered by the external tocogram. All
      contractions recorded by external tocogram were also registered by the
      dynamometer. Handgrip force was moderately correlated with pain scores on the
      NRS. Mean handgrip force during contractions had the highest correlation
      coefficient (Pearson's r=0.67) compared with peak handgrip force (r=0.56) and
      area under the curve of handgrip force (r=0.55). CONCLUSIONS: Pain intensity and
      duration can be assessed continuously using handgrip force measured via a
      dynamometer. The feedback of intensity and duration of pain could optimize
      patient-controlled remifentantil application for obstetric analgesia and other
      situations of highly variable pain intensity.

PMID- 25996769
TI  - Corrigendum Re: MS Sanatani, M Kattan, DE Moulin. Initial pain management plans
      in response to severe pain indicators on oncology clinic previsit questionnaires.
      Pain Res Manag 2014;19(6):309-312.

PMID- 25996770
TI  - Orally administrated dipeptide Ser-Tyr efficiently stimulates noradrenergic
      turnover in the mouse brain.
AB  - In this study, we examined the effect of orally administrated dipeptides
      containing Tyr (Y) on the metabolism of catecholamines in mouse brains. We found
      that among eight synthetic dipeptides whose sequences are present frequently in
      soy proteins, Ser-Tyr (SY), Ile-Tyr, and Tyr-Pro had the highest apparent
      permeability coefficients in monolayers of human intestinal epithelial Caco-2
      cells. When administrated orally, SY markedly increased tyrosine content in the
      cerebral cortex compared to the vehicle control, Ile-Tyr, Tyr-Pro, and Y alone.
      The oral administration of SY more effectively increased 3-methoxy-4
      hydroxyphenylethyleneglycol, the principal metabolite of noradrenaline, in the
      cerebral cortex and hippocampus than did Ile-Tyr, Tyr-Pro, or Y alone. Central
      noradrenergic turnover was also markedly stimulated by SY administration. These
      in vivo observations strongly suggest that SY is more potent in boosting central
      catecholamine transmission, particularly the noradrenergic system, than Y alone
      or other dipeptides that include Y. 

PMID- 25996771
TI  - 16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of
      Bloodstream Infections: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid
      (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream
      infections through a systematic review and meta-analysis. METHODS: A computerized
      literature search was conducted to identify studies that assessed the diagnostic
      value of 16S rRNA gene PCR test for bloodstream infections. Study quality was
      assessed using the revised Quality Assessment of Diagnostic Accuracy Studies
      (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood
      ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and
      their 95% confidence intervals (95% CI) for each study. Summary receiver
      operating characteristic (SROC) curve was used to summarize overall test
      performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE
      12.0 software. RESULTS: Twenty-eight studies were included in our meta-analysis.
      Using random-effect model analysis, the pooled sensitivity, specificity, PLR,
      NLR, and DOR were 0.87 (95% CI, 0.85-0.89), 0.94 (95% CI, 0.93-0.95), 12.65 (95%
      CI, 8.04-19.90), 0.14 (95% CI, 0.08-0.24), and 116.76 (95% CI, 52.02-262.05),
      respectively. The SROC curve indicated that the area under the curve (AUC) was
      0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In
      addition, heterogeneity was statistically significant but was not caused by the
      threshold effect. CONCLUSION: Existing data suggest that 16S rRNA gene PCR test
      is a practical tool for the rapid screening of sepsis. Further prospective
      studies are needed to assess the diagnostic value of PCR amplification and DNA
      microarray hybridization of 16S rRNA gene in the future.

PMID- 25996772
TI  - Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid,
      and Strontium Levels in Adult Men According to the US 2011-2012 National Health
      and Nutrition Examination Survey.
AB  - BACKGROUND: Little is known regarding the effects of environmental exposure of
      chemicals on androgenic system in the general population. We studied 5,107
      subjects included in the National Health and Nutrition Examination Survey (2011
      2012). METHODS: Urinary, serum, and blood levels of 15 subclasses comprising 110
      individual chemicals were analyzed for their association with serum testosterone
      levels. The subjects were divided into high and low testosterone groups according
      to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of
      individual chemicals in association with testosterone were estimated using
      logistic regression after adjusting for age, ethnicity, cotinine, body mass
      index, creatinine, alcohol, and the poverty income ratio. RESULTS: Adjusted ORs
      for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07,
      4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the
      association between urinary mandelic acid, and strontium quartiles with low
      testosterone concentrations in adult men, respectively. However, no association
      was observed for the remaining chemicals with testosterone. CONCLUSIONS: The
      National Health and Nutrition Examination Survey data suggest that elevations in
      urinary mandelic acid, and strontium levels are negatively related to low serum
      testosterone levels in adult men.

PMID- 25996773
TI  - The use of a video laryngoscope by emergency medicine residents is associated
      with a reduction in esophageal intubations in the emergency department.
AB  - OBJECTIVES: The purpose of this investigation was to compare the incidence of
      esophageal intubations (EIs) when emergency medicine (EM) residents used a direct
      laryngoscope (DL) versus a video laryngoscope (VL) for intubation attempts in the
      emergency department (ED). METHODS: Prospectively collected continuous quality
      improvement data on tracheal intubations performed by EM residents in an academic
      ED over a 6-year period were retrospectively analyzed. Following each intubation,
      EM residents completed a data form with patient, intubation, and operator
      characteristics. Data collected included the method of intubation, drugs used,
      device(s) used, number of attempts, outcome of each attempt, occurrence of EIs,
      and occurrence of adverse events (hypoxemia, aspiration, dysrhythmia,
      hypotension, and cardiac arrest). The incidence of EI was compared between
      intubation attempts with a DL and with a VL (GlideScope((r)) or C-MAC((r)) ).
      Propensity score matching and conditional logistic regression were used to
      analyze the association between the intubation device (DL vs. VL) and EI.
      RESULTS: Over the 6-year period, 2,677 patients underwent 3,425 intubation
      attempts by EM residents with a DL or a VL. A DL was used in 1,530 attempts
      (44.7%) and a VL was used in 1,895 attempts (55.3%). There were 96 recognized EIs
      (2.8%). The incidence of EI when using a DL was 78 of 1,530 attempts (5.1%; 95%
      confidence interval [CI] = 4.1% to 6.3%) and when using a VL was 18 of 1,895
      attempts (1.0%; 95% CI = 0.6% to 1.5%). Based on the propensity score matched
      analysis, the odds ratio for the occurrence of an EI for DL versus VL was 6.9
      (95% CI = 3.3 to 14.4). Patients who had inadvertent EIs had a higher incidence
      of adverse events (49.5%; 95% CI = 38.9% to 60.0%) than patients in which EI did
      not occur (19.8%; 95% CI = 18.3% to 21.4%). CONCLUSIONS: The use of a VL by EM
      residents during an intubation attempt in the ED was associated with
      significantly fewer EIs compared to when a DL was used. Patients who had
      inadvertent EIs had significantly more adverse events than those who did not have
      EIs. EM residency training programs should consider using VLs for ED intubations
      to maximize patient safety when EM residents are performing intubation.

PMID- 25996774
TI  - Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle
      during Early Recovery from Eccentric Contractions.
AB  - Unaccustomed eccentric exercise is accompanied by muscle damage and impaired
      glucose uptake and glycogen synthesis during subsequent recovery. Recently, it
      was shown that the role and regulation of glycogen in skeletal muscle are
      dependent on its subcellular localization, and that glycogen synthesis, as
      described by the product of glycogen particle size and number, is dependent on
      the time course of recovery after exercise and carbohydrate availability. In the
      present study, we investigated the subcellular distribution of glycogen in fibers
      with high (type I) and low (type II) mitochondrial content during post-exercise
      recovery from eccentric contractions. Analysis was completed on five male
      subjects performing an exercise bout consisting of 15 x 10 maximal eccentric
      contractions. Carbohydrate-rich drinks were subsequently ingested throughout a 48
      h recovery period and muscle biopsies for analysis included time points 3, 24 and
      48 h post exercise from the exercising leg, whereas biopsies corresponding to
      prior to and at 48 h after the exercise bout were collected from the non
      exercising, control leg. Quantitative imaging by transmission electron microscopy
      revealed an early (post 3 and 24 h) enhanced storage of intramyofibrillar
      glycogen (defined as glycogen particles located within the myofibrils) of type I
      fibers, which was associated with an increase in the number of particles. In
      contrast, late in recovery (post 48 h), intermyofibrillar, intramyofibrillar and
      subsarcolemmal glycogen in both type I and II fibers were lower in the exercise
      leg compared with the control leg, and this was associated with a smaller size of
      the glycogen particles. We conclude that in the carbohydrate-supplemented state,
      the effect of eccentric contractions on glycogen metabolism depends on the
      subcellular localization, muscle fiber's oxidative capacity, and the time course
      of recovery. The early enhanced storage of intramyofibrillar glycogen after the
      eccentric contractions may entail important implications for muscle function and
      fatigue resistance. 

PMID- 25996775
TI  - Management of presacral tumors: Our experience with posterior approach.
AB  - INTRODUCTION: Presacral tumors are a rare variety of space occupying lesions
      arising in the presacral space. Most of the tumors are congenital in origin. Due
      to obscure anatomic location, difficult surgical approach and etiological
      heterogeneity, tumors arising here pose a diagnostic and therapeutic challenge.
      We report our experience of 10 cases of presacral tumors with posterior approach
      being used in 6. MATERIALS AND METHODS: A retrospective analysis was conducted on
      10 cases of presacral tumors managed at our hospital during a period of 14 months
      (May 2013-July 2014). 9 cases were operated while one had advanced disease and
      was referred for palliative care. Complete en bloc excision of the mass was
      possible in 8 cases. Finally, presenting complaints, clinical diagnosis, surgical
      procedure and histopahological findings of the cases were studied. RESULTS: All
      of our patients were females in the age group of 18-50 (mean 28.4) years. The
      pathological findings included schwannoma, leiomyosarcoma, hemangiopericytoma,
      neurofibroma, paraganglioma and rest were developmental cysts. 6 cases were
      managed using the posterior approach and rest by anterior approach. There was no
      major complication or mortality in the follow up. CONCLUSION: Complete surgical
      excision remains the mainstay of therapy. Surgical approach depends upon the
      location, size, local invasion and surgical expertise of the surgeon. Benign
      tumors have a good prognosis while the prognosis in malignant tumors remains
      guarded due to difficulty in obtaining safe resection margins. Posterior approach
      is an attractive option for low lying, benign tumors that is more direct, with
      better exposure and quicker recovery.

PMID- 25996776
TI  - Endovascular management of renal artery aneurysm rupture in pregnancy - A case
      report.
AB  - INTRODUCTION: Renal artery aneurysm rupture is an extremely rare cause of acute
      abdominal pain and haemodynamic instability in pregnancy. Due to its rarity, the
      diagnosis may not be immediately considered, and therefore there is a high
      associated mortality rate for both mother and fetus. PRESENTATION OF CASE: We
      present a case of a 41-year old primigravida who presented to the obstetricians
      at 22 weeks' gestation with severe abdominal pain, shock and fetal loss. A
      bleeding renal artery aneurysm was discovered at laparotomy and radiologically
      coiled with sacrifice of the left kidney. Treatment of a contralateral aneurysm
      by autotransplantation of the remaining kidney allowed for preservation of
      residual renal function. DISCUSSION: Surgical acute abdominal presentations can
      be difficult to interpret in pregnant patients. Pregnancy is known to be a
      contributing risk factor for spontaneous rupture of renal artery aneurysms, an
      otherwise rare mode of aneurysm presentation. Prompt use of imaging to diagnose
      and treat non-obstetric causes of the acute abdomen should not be delayed because
      of perceived risks to the fetus. Endovascular arrest of aneurysmal haemorrhage
      may be more effect in the context of a gravid uterus than surgical management.
      CONCLUSION: In the shocked pregnant patient with an acute abdominal presentation,
      visceral artery aneurysm rupture may be comparatively more common, and should be
      considered in the absence of other localizing symptoms. Prompt interventional
      radiological treatment may be lifesaving in such cases.

PMID- 25996777
TI  - Integrating ontogenetic shift, growth and mortality to determine a species'
      ecological role from isotopic signatures.
AB  - Understanding species linkages and energy transfer is a basic goal underlying any
      attempt at ecosystem analysis. Although the first food-web studies were based on
      gut contents of captured specimens, the assessment of stable isotopes, mainly
      delta13C and delta15N, has become a standard methodology for wide-range analyses
      in the last 30 years. Stable isotopes provide information on the trophic level of
      species, food-web length, and origin of organic matter ingested by consumers. In
      this study, we analyzed the ontogenetic variability of delta13C and delta15N
      obtained from samples of three Neotropical fish species: silver sardine
      (Lycengraulis grossidens, n=46), white lambari (Cyanocharax alburnus, n= 26), and
      the red-tail lambari (Astyanax fasciatus, n=23) in Pinguela Lagoon, southern
      Brazil. We developed a new metric, called the Weighted Isotopic Signature (phi
      15N or phi 13C, 0/00), that incorporates ontogenetic variability, body growth,
      and natural mortality into a single number. 

PMID- 25996778
TI  - Acute and Chronic Toxicity of Nitrate to Early Life Stages of Zebrafish--Setting
      Nitrate Safety Levels for Zebrafish Rearing.
AB  - Recirculating aquaculture systems (RAS) have been widely used for zebrafish
      rearing, allowing holding of many thousands of fish at high densities. Water
      quality in RAS largely depends on biofilters that ultimately convert the
      extremely toxic ammonia excreted by fish into the much less toxic nitrate.
      However, when water renewal is minimal in RAS, nitrate can accumulate to high
      enough levels to negatively impact fish welfare and performance. Therefore, the
      setting of safety levels of nitrate for zebrafish should be a priority to avoid
      unwanted effects in both the intensive production of this species and research
      outputs. The present study aimed to define nitrate safety levels for zebrafish
      based on acute and chronic toxicity bioassays in early life stages of this
      species. Acute bioassays revealed ontogenetic changes in response to high nitrate
      levels. Based on NOEC (no observed effect concentration) values, safety levels
      should be set at 1450, 1855, and 1075 mg/L NO3(-)-N to prevent acute lethal
      effects in embryos, newly-hatched larvae, and swim-up larvae, respectively. In
      the chronic bioassay, larvae were exposed to nitrate concentrations of 50, 100,
      200, and 400 mg/L NO3(-)-N during the entire larval period (23 days). No negative
      effects were observed either on larval performance or condition at concentrations
      up to 200 mg/L NO3(-)-N. However, at 400 mg/L NO3(-)-N, survival drastically
      decreased and fish showed reduced growth and evidence of morphological
      abnormalities. Accordingly, a safety level of 200 mg/L NO3(-)-N is recommended
      during the larval rearing of zebrafish to prevent negative impacts on juvenile
      production.

PMID- 25996780
TI  - Low Vitamin D Levels: Are Associated with Both Iron Deficiency and Anemia in
      Children and Adolescents?
AB  - We have read, with great interest, the recent article by Lee. In this excellent
      study, the authors investigated the association between vitamin D deficiency and
      anemia in a nationally representative sample of Korean children and adolescents.
      They concluded that vitamin D deficiency is associated with increased risk of
      anemia, especially iron deficiency anemia, in healthy female children and
      adolescents. We appreciate and congratulate the authors for having addressed such
      an important issue. However, we have some concerns regarding this report, which
      we would like to share with you. As a result, further studies are needed for the
      association between vitamin D deficiency and anemia. Factors affecting Vitamin D
      status and anemia such as measurement method, nutrition, medications, and
      infections should be considered to conclude an association between vitamin D and
      anemia. Therefore, we think that considering these confounders would add value to
      this well-written article. 

PMID- 25996779
TI  - Subtyping Somatic Tinnitus: A Cross-Sectional UK Cohort Study of Demographic,
      Clinical and Audiological Characteristics.
AB  - Somatic tinnitus is the ability to modulate the psychoacoustic features of
      tinnitus by somatic manoeuvres. The condition is still not fully understood and
      further identification of this subtype is essential, particularly for the purpose
      of establishing protocols for both its diagnosis and treatment. This study aimed
      to investigate the characteristics of somatic tinnitus within a large UK cohort
      using a largely unselected sample. We believe this to be relatively unique in
      comparison to current literature on the topic. This was investigated by using a
      total of 608 participant assessments from a set of recognised tinnitus and
      audiology measures. Results from a set of chi-square tests of association found
      that amongst the individuals with somatic tinnitus, a higher proportion had
      pulsatile tinnitus (different from heartbeat), were under the age of 40, reported
      variation in the loudness of their tinnitus and reported temporomandibular joint
      (TMJ) disorder. The same pattern of results was confirmed using a multivariate
      analysis of the data based on logistic regression. These findings have strong
      implications towards the profiling of somatic tinnitus as a distinct subtype of
      general tinnitus. 

PMID- 25996781
TI  - Luminescence energy transfer detection of PSA in red region based on Mn2+
      enhanced NaYF4:Yb, Er upconversion nanorods.
AB  - A new turn-on luminescence energy transfer (LET) system has been designed for the
      detection of prostate specific antigen (PSA, a cancer marker) that utilizes
      Mn(2+)-enhanced long wavelength luminescence NaYF4:Yb, Er upconversion nanorods
      as the donor and gold nanorods as the acceptor. The Mn(2+)-doped NaYF4:Yb,Er
      upconversion luminescence nanorods with an emission peak located in the red
      region were synthesized. The presence of Mn(2+) markedly increased the
      luminescence intensity over that of the NaYF4:Yb, Er upconversion nanomaterials
      (excited by a 980 nm continuous wavelength laser). The surfaces of Mn(2+)-doped
      NaYF4:Yb, Er upconversion nanorods were modified with poly(acrylic acid).
      Antibodies against prostate specific antigen were bound to the surface of the
      carboxyl-functionalized upconversion nanorods, which acted as the energy donor in
      this LET system. Gold nanorods with an absorption band at ~666 nm were
      synthesized by the seed growth method, acted as the energy acceptor. The emission
      band of the upconversion nanorods overlapped well with the absorption band of the
      gold nanorods. The luminescence was quenched because of the electrostatic
      interactions that shortened the distance between the donor (negatively charged)
      and the accepter (positively charged).When the PSA antigen was added into the
      system, the energy acceptor and the energy donors were separated because the
      binding affinity between PSA and anti-PSA was greater than the electrostatic
      interactions, and thereby the luminescence was recovered. The linear range of
      detecting PSA was from 0.1172 to 18.75 ng/mL (R=0.995), with a limit of detection
      for PSA as low as 0.1129 ng/mL. The method was successfully applied to the
      sensing of PSA in human serum samples.

PMID- 25996782
TI  - Formation of Carbocycles via a 1,4-Rh Shift Triggered by a Rhodium-Catalyzed
      Addition of Terminal Alkynes to 3,3-Diarylcyclopropenes.
AB  - The catalytic addition of terminal alkynes to 3,3-diarylcyclopropenes in the
      presence of a Rh(I)/binap complex proceeded to give the cycloaddition products in
      good yields, where a 1,4-Rh shift is involved as a key step. 

PMID- 25996783
TI  - International external quality assessment study for molecular detection of Lassa
      virus.
AB  - Lassa virus (LASV) is a causative agent of hemorrhagic fever in West Africa. In
      recent years, it has been imported several times to Europe and North America. The
      method of choice for early detection of LASV in blood is RT-PCR. Therefore, the
      European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) performed
      an external quality assessment (EQA) study for molecular detection of LASV. A
      proficiency panel of 13 samples containing various concentrations of inactivated
      LASV strains Josiah, Lib-1580/121, CSF, or AV was prepared. Samples containing
      the LASV-related lymphocytic choriomeningitis virus (LCMV) and negative sera were
      included as specificity controls. Twenty-four laboratories from 17 countries (13
      European, one African, one Asian, two American countries) participated in the
      study. Thirteen laboratories (54%) reported correct results, 4 (17%) laboratories
      reported 1 to 2 false-negative results, and 7 (29%) laboratories reported 3 to 5
      false-negative results. This EQA study indicates that most participating
      laboratories have a good or acceptable performance in molecular detection of
      LASV. However, several laboratories need to review and improve their diagnostic
      procedures. 

PMID- 25996784
TI  - Role of alpha- and beta-Synucleins in the Axonal Pathology of Parkinson's Disease
      and Related Synucleinopathies.
AB  - Axonal swellings are histological hallmarks of axonopathies in various types of
      disorders in the central nervous system, including neurodegenerative diseases.
      Given the pivotal role of axonopathies during the early phase of
      neurodegenerative process, axonal swellings may be good models which may provide
      some clues for early pathogenesis of alpha-synucleinopathies, including
      Parkinson's disease and dementia with Lewy bodies (DLB). In this mini-review,
      such a possibility is discussed based on our recent studies as well as other
      accumulating studies. Consistent with the current view that dysfunction in the
      autophagy-lysosomal system may play a major role in the formation of axonal
      swellings, our studies showed globule, small axonal swellings, derived from
      transgenic mice expressing either human wild-type alpha-synuclein (alphaS
      globule) or DLB-linked P123H beta-synuclein (betaS-globule), contained
      autophagosome-like membranes. However, other pathological features, such as
      abnormal mitochondria, enhanced oxidative stress and LRRK2 accumulation, were
      observed in the alphaS-globules, but not in the betaS-globules. Collectively, it
      is predicted that alphaS and betaS may be involved in axonopathies through
      similar but distinct mechanisms, and thus, contribute to diverse axonal
      pathologies. Further studies of the axonal swellings may lead to elucidating the
      pathogenic mechanism of early alpha-synucleinopathies and illuminating a strategy
      for a disease-modifying therapy against these devastating disorders. 

PMID- 25996785
TI  - Transcriptional and metabolic alternations rebalance wheat grain storage protein
      accumulation under variable nitrogen and sulfur supply.
AB  - Wheat (Triticum aestivum L.) grain storage proteins (GSPs) are major determinants
      of flour end-use value. Biological and molecular mechanisms underlying the
      developmental and nutritional determination of GSP accumulation in cereals are as
      yet poorly understood. Here we timed the accumulation of GSPs during wheat grain
      maturation relative to changes in metabolite and transcript pools in different
      conditions of nitrogen (N) and sulfur (S) availability. We found that the N/S
      supply ratio modulated the duration of accumulation of S-rich GSPs and the rate
      of accumulation of S-poor GSPs. These changes are likely to be the result of
      distinct relationships between N and S allocation, depending on the S content of
      the GSP. Most developmental and nutritional modifications in GSP synthesis
      correlated with the abundance of structural gene transcripts. Changes in the
      expression of transport and metabolism genes altered the concentrations of
      several free amino acids under variable conditions of N and S supply, and these
      amino acids seem to be essential in determining GSP expression. The comprehensive
      data set generated and analyzed here provides insights that will be useful in
      adapting fertilizer use to variable N and S supply, or for breeding new cultivars
      with balanced and robust GSP composition. 

PMID- 25996786
TI  - Computed Tomographic Analysis of the Mandibular Body and Ramus in Japanese
      Patients: Relevance to Bone Harvesting From the Mandibular Ramus.
AB  - PURPOSE: The aims of this study were to use computed tomography (CT) imaging to
      determine the anatomical features of the mandibular body and ramus in Japanese
      subjects and to relate the findings to bone harvesting from the mandibular ramus.
      MATERIALS AND METHODS: The mandibles of 100 patients (28 males and 72 females)
      under dental implant treatment plan were observed on CT imaging (slice thickness,
      0.625 mm). The linear distance between the superior aspect of the inferior
      alveolar nerve canal and the alveolar crest (distance A), the linear distance
      between the buccal aspect of the inferior alveolar nerve canal and the buccal
      cortical bone (distance B), the thickest width of the buccal cortical bone
      (distance C), and the thinnest width of the buccal cortical bone (distance D)
      were measured in the same coronal plane at 4 specific locations (section 1: the
      distal aspect of the first molar, section 2: the distal aspect of the second
      molar, section 3: the 10 mm distal aspect of the second molar, and section 4: the
      15 mm distal aspect of the second molar). RESULTS: In the measurement of distance
      A, the minimum section among the male subjects was section 2 (12.55 +/- 3.00 mm),
      whereas among the females, the minimum section was section 3 (11.82 +/- 2.85 mm).
      In the distance B measurements, the maximum value was at section 2 (males: 6.36
      +/- 1.33 mm, females: 6.32 +/- 1.39 mm) and the minimum value was at section 4
      (males: 3.85 +/- 1.74 mm, females: 4.75 +/- 1.47 mm). Regarding the distance C
      measurements, the values of all subjects ranged from 3.10 to 4.41 mm, and the
      distance D values were approximately 2 mm. CONCLUSION: In Japanese patients, a
      rectangular piece of cortical bone up to 2 mm thickness may be harvested from the
      ramus, the length of the rectangular graft may approach 26 mm, and the height may
      be 10 mm for the safest harvesting from the mandibular ramus.

PMID- 25996787
TI  - A Clinical Study Evaluating Changes in the Microbial Flora Around Dental Implants
      During Various Stages of Implant Restoration.
AB  - PURPOSE: This study evaluated the microbial colonization of dental implants in
      healthy patients before placing the implants and during the various stages of
      implant treatment. MATERIALS AND METHODS: Saliva (in completely edentulous
      patients) and gingival crevicular fluid samples (in partially edentulous
      patients) were collected from patients and analyzed to estimate the growth of
      microorganisms after culture. Samples were collected during 10 phases of implant
      placement and prosthesis insertion. Sixty dental implants, 18 of NobelReplace
      Select (Nobel Biocare) and 42 of GSIII/TSIII (Osstem), were evaluated. The
      microbial titer was estimated in colony-forming units (CFU) per milliliter. The
      percentage distribution of the organisms during the various phases was noted and
      the average was compared. RESULTS: Most prevalent microorganism found was gram
      positive Streptococci (3.59 * 10 CFU/mL). The titer of Fusobacterium nucleatum,
      Porphyromonas gingivalis, Prevotella intermedia, and Pseudomonas being 0.42 * 10
      CFU/ml, 0.15 * 10 CFU/mL, 0.09 * 10 CFU/mL, and 0.03 * 10 CFU/mL, respectively.
      The titer of these organisms noted during the experimental phase was low. A
      similarity was observed in the maximum colony-forming unit per milliliter between
      baseline and completion of implant therapy indicating establishment of
      equilibrium. CONCLUSION: Regular microbial evaluation along with clinical and
      radiographic monitoring could help in recognizing the potential for
      periimplantitis and in prevention of the same.

PMID- 25996788
TI  - Levels of Myeloperoxidase and Alkaline Phosphatase in Periimplant Sulcus Fluid in
      Health and Disease and After Nonsurgical Therapy.
AB  - PURPOSE: The study evaluated 2 biomarkers (myeloperoxidase [MPO] and alkaline
      phosphatase) along with clinical parameters in periimplant sulcus fluid (PISF) in
      conditions of periimplant health and disease. The effect of nonsurgical therapy
      was also evaluated on the biochemical and clinical parameters in diseased
      implants at 3 months after the baseline. MATERIALS AND METHODS: A total number of
      30 implants were studied in 20 subjects and divided into healthy group (group 1)
      and periimplant disease group (group 2). PISF was collected in both groups along
      with recording of clinical parameters. The periimplant disease group was then
      instituted a nonsurgical anti-infective therapy. The clinical and biochemical
      parameters were evaluated and compared at baseline and at the end of 3 months.
      RESULTS: Group 2 showed statistically significant higher PISF MPO values at
      baseline as compared with groups 1 and 2 (at 3 months) (P < 0.001). Also,
      difference in the mean value of PISF MPO in group 2 (at 3 months) was greater
      than that in group 1 and was statistically nonsignificant (P = 1.85). CONCLUSION:
      Within confines of the study, it can be concluded that evaluation of biochemical
      markers in PISF can be a useful diagnostic tool to aid the clinician in decision
      making regarding the management of the condition.

PMID- 25996789
TI  - Multiplexed peptide analysis using data-independent acquisition and Skyline.
AB  - Here we describe the use of data-independent acquisition (DIA) on a Q-Exactive
      mass spectrometer for the detection and quantification of peptides in complex
      mixtures using the Skyline Targeted Proteomics Environment (freely available
      online at http://skyline.maccosslab.org). The systematic acquisition of mass
      spectrometry (MS) or tandem MS (MS/MS) spectra by DIA is in contrast to DDA, in
      which the acquired MS/MS spectra are only suitable for the identification of a
      stochastically sampled set of peptides. Similarly to selected reaction monitoring
      (SRM), peptides can be quantified from DIA data using targeted chromatogram
      extraction. Unlike SRM, data acquisition is not constrained to a predetermined
      set of target peptides. In this protocol, a spectral library is generated using
      data-dependent acquisition (DDA), and chromatograms are extracted from the DIA
      data for all peptides in the library. As in SRM, quantification using DIA data is
      based on the area under the curve of extracted MS/MS chromatograms. In addition,
      a quality control (QC) method suitable for DIA based on targeted MS/MS
      acquisition is detailed. Not including time spent acquiring data, and time for
      database searching, the procedure takes ~1-2 h to complete. Typically, data
      acquisition requires roughly 1-4 h per sample, and a database search will take
      0.5-2 h to complete. 

PMID- 25996790
TI  - A ring barrier-based migration assay to assess cell migration in vitro.
AB  - Cell migration is a key feature of virtually every biological process, and it can
      be studied in a variety of ways. Here we outline a protocol for the in vitro
      study of cell migration using a ring barrier-based assay. A 'barrier' is inserted
      in the culture chamber, which prevents cells from entering a defined area. Cells
      of interest are seeded around this barrier, and after the formation of a
      peripheral monolayer the barrier is removed and migration into the cell-free area
      is monitored. This assay is highly reproducible and convenient to perform, and it
      allows the deduction of several parameters of migration, including total and
      effective migration, velocity and cell polarization. An advantage of this assay
      over the conventional scratch assay is that the cells move over an unaltered and
      virgin surface, and thus the effect of matrix components on cell migration can be
      studied. In addition, the cells are not harmed at the onset of the assay. Through
      computer automation, four individual barrier assays can be monitored at the same
      time. The procedure can be used in a 12-well standard plate allowing higher
      throughput, or it can be modified to perform invasion assays. The basic procedure
      takes 2-3 d to complete. 

PMID- 25996791
TI  - Cobalt-based nanocatalysts for green oxidation and hydrogenation processes.
AB  - This protocol describes the preparation of cobalt-based nanocatalysts and their
      applications in environmentally benign redox processes for fine chemical
      synthesis. The catalytically active material consists of nanoscale Co3O4
      particles surrounded by nitrogen-doped graphene layers (NGrs), which have been
      prepared by pyrolysis of phenanthroline-ligated cobalt acetate on carbon. The
      resulting materials have been found to be excellent catalysts for the activation
      of both molecular oxygen and hydrogen; in all tested reactions, water was the
      only by-product. By applying these catalysts, green oxidations of alcohols and
      hydrogenation of nitroarenes for the synthesis of nitriles, esters and amines are
      demonstrated. The overall time required for catalyst preparation and for redox
      reactions is 35 h and 10-30 h, respectively. 

PMID- 25996792
TI  - Nonanesthesia magnetic resonance enterography in young children: feasibility,
      technique, and performance.
AB  - OBJECTIVES: The aim of the present study was to demonstrate the effectiveness and
      cost savings of a nonanesthesia approach to magnetic resonance enterography (MRE)
      in 14 young pediatric patients (age 4-7 years) with clinically suspected early
      onset inflammatory bowel disease using an MRE protocol. METHODS: MRE was
      performed using a combination of an abbreviated imaging protocol, magnetic
      resonance imaging video goggles, and Child Life Services support. MRE results
      were correlated with both colonoscopy and pathology results using Pearson
      correlation coefficient. Sensitivity, specificity, and positive and negative
      predictive values were calculated. RESULTS: MRE was performed successfully in 13
      of 14 patients (age range 4 years 0 months to 7 years 6 months). MRE findings
      matched with results in 12 of 13 patients in whom colonoscopy was successfully
      performed. Both MRE and colonoscopy demonstrated a high specificity (100%) and a
      positive predictive value (100%), but a low sensitivity (43%) and a negative
      predictive value (50%). CONCLUSIONS: MRE can be successfully performed in
      children ages 4 to 7 years using this approach. In addition to decreased risks to
      the child, the lack of anesthesia also offers a potential overall cost reduction.

PMID- 25996793
TI  - Propofol-ketamine and propofol-fentanyl combinations for nonanesthetist
      administered sedation.
AB  - OBJECTIVES: There is a need to compare propofol requirement between propofol
      ketamine (PK) and propofol-fentanyl (PF) given as nonanesthetist-administered
      propofol sedation during pediatric esophagogastroduodenoscopy (EGD). METHODS: The
      study was a parallel-group, randomized, double-blind comparison of the need for
      additional doses of propofol in the first minute after sedation induction between
      PK and PF, administered by rotating trainees in pediatrics for sedation during
      pediatric EGD. A total of 95 children with American Society of Anesthesiologists
      class I to III between 3 and 12 years undergoing EGD were included and randomized
      to either of the groups. After midazolam premedication, children received either
      0.5 mg/kg ketamine (PK) or 1 MUg/kg of fentanyl (PF) followed by a mandatory 1
      mg/kg of propofol. Additional doses of propofol of 0.5 mg/kg each were given to
      achieve sedation induction (modified Ramsay scale level 6), and further doses
      were administered during the procedure as required. A total of 92 children (PK, n
      = 47; PF, n = 45) were analyzed. P < 0.05 was considered significant. RESULTS:
      There was no difference in the propofol dose required for successful scope
      introduction and also in the need for additional propofol doses and the total
      additional propofol doses required in the first minute after sedation induction.
      Propofol injection pain was higher in the PF group (odds ratio 1.78). The adverse
      events and recovery time were similar. There was no escalation of care, airway
      intubations, death, or disability. CONCLUSIONS: Nonanesthetist-administered
      propofol sedation is feasible in teaching hospitals. Propofol requirement is
      similar in both PK and PF combination regimens, but the lower frequency of
      propofol injection pain may favor the use of PK.

PMID- 25996794
TI  - Parental and youth understanding of the informed consent process for pediatric
      endoscopy.
AB  - OBJECTIVES: Informed consent (IC) is an essential communication between
      patient/representative and physician that acknowledges patient autonomy; assent
      is the equivalent process performed between youth and physician. For clinical
      procedures involving youth, only the IC process between guardian/parent and
      physician is required to be performed. Nevertheless, experts recommend that youth
      undergo assent whenever possible. In the present study, we explored both parental
      and youth understanding of required IC elements in IC discussions before
      pediatric endoscopy. METHODS: Following signing of IC documents on the day of
      endoscopy at a tertiary care academic medical center, youth and their parents
      underwent structured interviews to assess comprehension of key elements of the IC
      process. RESULTS: A total of 88 children and adolescents and their parents were
      evaluated. Two youth and 12 parents demonstrated comprehensive understanding of
      key IC elements for pediatric endoscopy. Suboptimal youth understanding was
      demonstrated for nature of the procedure (25% with adequate understanding) and
      related risks (17%), and alternatives (14%) to the procedure. Suboptimal parental
      understanding was demonstrated for procedure alternatives (24%). Youth overall
      understanding of IC varied by age, whereas parental global understanding of IC
      varied by physician. CONCLUSIONS: Understanding of IC performed for pediatric
      endoscopy could be improved in both parents and youth. Our findings suggest that
      interventions targeting parents, youth, and physicians may be helpful. Further
      study is needed to determine whether our findings are representative of IC
      understanding at other pediatric endoscopy centers.

PMID- 25996795
TI  - Predicting Mortality in Systemic Sclerosis-Associated Interstitial Lung Disease
      Using Risk Prediction Models Derived From Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: Mortality risk prediction tools have been developed in idiopathic
      pulmonary fibrosis, however, it is unknown whether these models accurately
      estimate mortality in systemic sclerosis-associated interstitial lung disease
      (SSc-ILD). METHODS: Four baseline risk prediction models--the Composite
      Physiologic Index, the Interstitial Lung Disease-Gender, Age, Physiology Index,
      the du Bois index, and the modified du Bois index--were calculated for patients
      recruited from a specialized SSc-ILD clinic. Each baseline model was assessed
      using logistic regression analysis with 1-year mortality as the outcome variable.
      Discrimination was quantified using the area under the receiver operating
      characteristic curve. Calibration was assessed using the goodness-of-fit test.
      The incremental prognostic ability of additional predictor variables was
      determined by adding prespecified variables to each baseline model. RESULTS: The
      156 patients with SSc-ILD completed 1,294 pulmonary function tests, 725 6-min
      walk tests, and 637 echocardiograms. Median survival was 15.0 years from the time
      of SSc-ILD diagnosis. All baseline models were significant predictors of 1-year
      mortality in SSc-ILD. The modified du Bois index had an area under the receiver
      operating characteristic curve of 0.84, compared with 0.77 to 0.81 in the other
      models. Calibration was acceptable for the modified du Bois index, but was poor
      for the other models. All baseline models include FVC and 6-min walk distance was
      identified as an additional independent predictor of 1-year mortality.
      CONCLUSIONS: The modified du Bois index has good discrimination and calibration
      for the prediction of 1-year mortality in SSc-ILD. FVC and 6-min walk distance
      are important independent predictors of 1-year mortality in SSc-ILD.

PMID- 25996796
TI  - Carotenoid bioaccessibility in pulp and fresh juice from carotenoid-rich sweet
      oranges and mandarins.
AB  - Citrus fruits are a good source of carotenoids for the human diet; however,
      comparative studies of carotenoids in different citrus food matrices are scarce.
      In this work the concentration and bioaccessibility of carotenoids in sweet
      oranges and mandarins with marked differences in carotenoid composition were
      evaluated in pulp and compared to those in fresh juice. The pulp and juice of the
      red-fleshed Cara Cara sweet orange variety was highly rich in carotenes (mainly
      lycopene and phytoene) compared to standard Navel orange, while beta
      cryptoxanthin and phytoene predominated in mandarins. Total carotenoid content in
      the pulp of the ordinary Navel orange and in the red-fleshed Cara Cara orange, as
      well as in the Clementine mandarin were higher than in the corresponding juices,
      although individual carotenoids were differentially affected by juice
      preparation. Bioaccessibility of the bioactive carotenoids (the ones described to
      be absorbed by humans) was greater in both pulp and juice of the carotenoid-rich
      Cara Cara orange compared to the Navel orange while increasing levels of beta
      cryptoxanthin were detected in the bioaccessible fractions of pulp and juice of
      mandarins postharvest stored at 12  degrees C compared to freshly-harvested
      fruits. Overall, results indicated that higher soluble bioactive carotenoids from
      citrus fruits and, consequently, potential nutritional and health benefits are
      obtained by the consumption of pulp with respect to fresh juice.

PMID- 25996798
TI  - Effects of Water on Solvation Layers of Imidazolium-Type Room Temperature Ionic
      Liquids on Silica and Mica.
AB  - Effects of the addition of water on solvation layers of imidazolium-type room
      temperature ionic liquids (RT-ILs) have been studied through force curve
      measurements of atomic force microscopy (AFM). Two kinds of RT-ILs were employed
      in this study; one is a hydrophilic RT-IL (1-butyl-3-methylimidazolium
      tetrafluoroborate, BmimBF4), and the other is a hydrophobic one (1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide, EmimTFSI). These RT-ILs form
      solvation layers on hydrophilic solid substances (i.e., silica and mica) in the
      absence of added water. The addition of water into BmimBF4 resulted in the
      disruption of the solvation layers and then the formation of an interfacial water
      phase on silica. In contrast, the formation of the interfacial water phase was
      not evidenced on mica because of the absence of hydrogen-bonding sites on the
      mica surface. Interestingly, the addition of water into EmimTFSI induced the
      formation of the interfacial water phase on the two solid surfaces. In the
      EmimTFSI system, importantly, significantly greater adhesion forces were observed
      on silica than on mica. This reflects the different formation mechanisms of the
      interfacial water phase on the two solid surfaces. We conclude that the hydrogen
      bonding is a key factor in determining whether water molecules can be adsorbed on
      the solid surfaces, but it is also necessary to take into account the
      hydrophilic/hydrophobic nature of the RT-ILs. 

PMID- 25996799
TI  - Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of
      Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic
      Hepatocellular Carcinoma.
AB  - In this study, galactose-based nanogels were prepared by reversible addition
      fragmentation chain transfer process to facilitate the targeted delivery of
      iodoazomycin arabinofuranoside (IAZA), a clinical drug for imaging solid hypoxic
      tumors, and evaluate its role in hypoxia-selective (radio)theranostic (therapy +
      diagnostic) management of therapy-resistant cancer cells. The nanogels have a
      cross-linked temperature-responsive core and a dense carbohydrate shell. Their
      thermoresponsive nature allowed the controlled encapsulation of IAZA drug for
      targeted delivery and release in hypoxic hepatocellular carcinoma via
      asialoglycoprotein receptor-mediated uptake. The synthesized nanogel-IAZA
      delivery systems demonstrated a stable, nonburst release of IAZA over 10 h with
      up to 0.6 mM loading capacity of IAZA within the nanogel. The cytotoxicity
      evaluations of the nanogels demonstrated that they are relatively nontoxic in
      multiple cell lines. The radiosensitization studies indicated that IAZA in
      encapsulated form offers a superior radiosensitization of hypoxic cells
      (sensitizer enhancement ratio for IAZA alone, 1.33; 1.62 for nanogel encapsulated
      IAZA). These studies suggest that galactose-based nanogels may serve as a
      versatile drug delivery system for IAZA (and other azomycin-based agents) and
      enable its hypoxia-selective multimodal theranostic applications to manage
      hypoxic solid (hepatocellular) tumors by facilitating position/single photon
      emission tomography-based imaging, external beam radiation therapy, and in situ
      molecular radiotherapy.

PMID- 25996800
TI  - One lipid, two synaptic plasticity pathways.
AB  - A new study identifies an unexpected role for lysophosphatidic acid in modulating
      the strength of both excitatory and inhibitory synapses in the brain, but by
      different mechanisms. Read the accompanying Research Article. 

PMID- 25996802
TI  - Kinetically Enhanced Approach for Rapid and Tunable Self-Assembly of Rod-Coil
      Block Copolymers.
AB  - A facile approach is reported to process rod-coil block copolymers (BCPs) into
      highly ordered nanostructures in a rapid, low-energy process. By introducing a
      selective plasticizer into the rod-coil BCPs during annealing, both the annealing
      temperature and time to achieve thermodynamic equilibrium and highly ordered
      structures can be decreased. This process improvement is attributed to enhanced
      chain mobility, reduced rod-rod interaction, and decreased rod-coil interaction
      from the additive. The novel method is based on kinetically facilitating
      thermodynamic equilibrium. The process requires no modification of polymer
      structure, indicating that a wide variety of desired polymer functionalities can
      be designed into BCPs for specific applications. 

PMID- 25996801
TI  - Cloning and characterization of farnesyl pyrophosphate synthase from the highly
      branched isoprenoid producing diatom Rhizosolenia setigera.
AB  - The diatom Rhizosolenia setigera Brightwell produces highly branched isoprenoid
      (HBI) hydrocarbons that are ubiquitously present in marine environments. The
      hydrocarbon composition of R. setigera varies between C25 and C30 HBIs depending
      on the life cycle stage with regard to auxosporulation. To better understand how
      these hydrocarbons are biosynthesized, we characterized the farnesyl
      pyrophosphate (FPP) synthase (FPPS) enzyme of R. setigera. An isolated 1465-bp
      cDNA clone contained an open reading frame spanning 1299-bp encoding a protein
      with 432 amino acid residues. Expression of the RsFPPS cDNA coding region in
      Escherichia coli produced a protein that exhibited FPPS activity in vitro. A
      reduction in HBI content from diatoms treated with an FPPS inhibitor,
      risedronate, suggested that RsFPPS supplies precursors for HBI biosynthesis.
      Product analysis by gas chromatography-mass spectrometry also revealed that
      RsFPPS produced small amounts of the cis-isomers of geranyl pyrophosphate and
      FPP, candidate precursors for the cis-isomers of HBIs previously characterized.
      Furthermore, RsFPPS gene expression at various life stages of R. setigera in
      relation to auxosporulation were also analyzed. Herein, we present data on the
      possible role of RsFPPS in HBI biosynthesis, and it is to our knowledge the first
      instance that an FPPS was cloned and characterized from a diatom. 

PMID- 25996803
TI  - Regioselective Tandem [4 + 1]-[4 + 2] Synthesis of Amino-Substituted
      Dihydroxanthones and Xanthones.
AB  - A highly convergent and operationally simple approach to mycotoxin-related 4
      amino-substituted 1-hydroxydihydroxanthones is described. The target compounds
      are obtained in one pot by the multicomponent reaction of 3-carbonylchromones,
      isocyanides, and nonsymmetric dienophiles. The reaction, which involves a tandem
      [4 + 1]-[4 + 2] cycloaddition, efficiently affords a variety of both monomeric
      and dimeric polysubstituted dihydroxanthones structurally similar to bioactive
      ergochromes. Further aromatization to the corresponding xanthones is readily
      achieved by treatment with DBU under microwave irradiation. 

PMID- 25996804
TI  - Elastin hydrolysate derived from fish enhances proliferation of human skin
      fibroblasts and elastin synthesis in human skin fibroblasts and improves the skin
      conditions.
AB  - BACKGROUND: Recent studies have shown that certain peptides significantly improve
      skin conditions, such as skin elasticity and the moisture content of the skin of
      healthy woman. This study aimed to investigate the effects of elastin hydrolysate
      on human skin. Proliferation and elastin synthesis were evaluated in human skin
      fibroblasts exposed to elastin hydrolysate and proryl-glycine (Pro-Gly), which is
      present in human blood after elastin hydrolysate ingestion. We also performed an
      ingestion test with elastin hydrolysate in humans and evaluated skin condition.
      RESULTS: Elastin hydrolysate and Pro-Gly enhanced the proliferation of
      fibroblasts and elastin synthesis. Maximal proliferation response was observed at
      25 ng mL(-1) Pro-Gly. Ingestion of elastin hydrolysate improved skin condition,
      such as elasticity, number of wrinkles, and blood flow. Elasticity improved by 4%
      in the elastin hydrolysate group compared with 2% in the placebo group.
      CONCLUSION: Therefore, elastin hydrolysate activates human skin fibroblasts and
      has beneficial effects on skin conditions.

PMID- 25996805
TI  - Laser-Evoked Potentials in Fibromyalgia: The Influence of Greater Occipital Nerve
      Stimulation on Cerebral Pain Processing.
AB  - OBJECTIVE: Fibromyalgia causes widespread musculo-skeletal pain in the four
      quadrants of the body. Greater occipital nerve stimulation has recently shown
      beneficial effects in fibromyalgia patients on pain, fatigue, and mood disorders.
      Laser-evoked potentials (LEPs) are used for research to understand the
      pathophysiological mechanisms of pain and to evaluate the effects of pain
      treatment. In fibromyalgia patients, LEPs tend to have a higher N2 amplitude, a
      tendency to shorter latencies, and patients have a lower pain threshold. Greater
      occipital nerve stimulation might exert a modulation of the medial pain pathways
      processing the affective motivational components of pain (unpleasantness) as well
      as the descending pain inhibitory pathways (reducing pain), both of which are
      contributing to the N2P2 peak. MATERIALS AND METHODS: To test this hypothesis,
      the authors performed LEPs in a group of fibromyalgia patients with and without
      greater occipital nerve stimulation. RESULTS: Occipital nerve stimulation does
      not alter the amplitudes of the LEP recordings, although a significant difference
      in latencies can be seen. More specifically, latencies of the N2P2 increased in
      the condition after stimulation, and especially at the Pz electrode. CONCLUSION:
      Our results suggest Occipital Nerve Stimulation (ONS) induces a modification of
      the balance between antinociceptive pain inhibitory pathways and pain-provoking
      pathways.

PMID- 25996806
TI  - Systemic cytosolic Ca(2+) elevation is activated upon wounding and herbivory in
      Arabidopsis.
AB  - Calcium ion (Ca(2+) ) signalling triggered by insect herbivory is an intricate
      network with multiple components, involving positive and negative regulators.
      Real-time, noninvasive imaging of entire Arabidopsis thaliana rosettes was
      employed to monitor cytosolic free calcium ([Ca(2+) ]cyt ) elevations in local
      and systemic leaves in response to wounding and Spodoptera littoralis feeding.
      Luminescence emitted by the cytosol-localized Ca(2+) reporter aequorin was imaged
      using a high-resolution photon-counting camera system. Spodoptera littoralis
      feeding on Arabidopsis induced both local and systemic [Ca(2+) ]cyt elevations.
      Systemic [Ca(2+) ]cyt signals were found predominantly in adjacent leaves with
      direct vascular connections to the treated leaf and appeared with a delay of 1 to
      2 min. Simulated herbivory by wounding always induced a local [Ca(2+) ]cyt
      response, but a systemic one only when the midrib was wounded. This systemic
      [Ca(2+) ]cyt response was suppressed by the presence of insect-derived oral
      secretions as well as in a mutant of the vacuolar cation channel, Two Pore
      Channel 1 (TPC1). Our results provide evidence that in Arabidopsis insect
      herbivory induces both local and systemic [Ca(2+) ]cyt signals that distribute
      within the vascular system. The systemic [Ca(2+) ]cyt signal could play an
      important signalling role in systemic plant defence.

PMID- 25996807
TI  - A role for novel lipid interactions in the dynamic recruitment of SNX27 to the T
      cell immune synapse.
AB  - SNX27 is a member of the sorting nexin family that plays an important role in the
      recycling of receptors from endosomes to the cell surface. In addition to a PX
      (Phox homology) domain that regulates its endosomal localization, SNX27 has a
      unique PDZ (Psd-95/Dlg/ZO1) domain and an atypical FERM (4.1, ezrin, radixin,
      moesin) domain that both function to bind short peptide sequence motifs in the
      cytoplasmic domains of the cargo receptors. Using the T cell immune synapse (IS)
      as a model for polarized protein recycling, we recently identified an additional
      mechanism that enhances SNX27 localization to the endosomal recycling compartment
      (ERC). Our study defined a phosphoinositide (PI) lipid-binding site within the
      SNX27 FERM domain, with a clear preference for bi- and triphosphorylated PIs,
      which may promote SNX27 localization to phosphatidylinositol-4,5-bisphosphate
      (PtdIns(4,5)P2) and/or PtdIns(3,4,5)P3-enriched membrane domains. Using
      fluorescently tagged lipid-binding probes, we studied the kinetics of distinct
      PIs in living T cells during IS formation. Our results suggest that
      PtdIns(3,4,5)P3 accumulates at the contact site simultaneously with early SNX27
      recruitment to the plasma membrane (PM), and this is partly controlled by by
      lipid binding through the FERM domain. These studies define 2 independent binding
      sites for PtdIns-derived lipids in SNX27, that contribute to the dynamic
      recruitment of SNX27 to distinct membranes during T cell activation. 

PMID- 25996808
TI  - Toxicity assessment of 2,4-D and MCPA herbicides in primary culture of fish
      hepatic cells.
AB  - In this study, we used primary cultures of fish hepatic cells as a tool for
      evaluating the effects of environmental contamination. Primary hepatic cell
      cultures derived from the subtropical fish Metynnis roosevelti were exposed to
      different concentrations (0.275, 2.75 and 27.5 MUg L(-1)) of the herbicides 2,4
      dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid
      (MCPA). Cellular respiratory activity was evaluated by polarography using three
      substrates: 0.5 M glucose, 0.5 M succinate and 0.5 M alpha-ketoglutarate.
      Significant changes were observed in cellular oxygen consumption with 0.5 M alpha
      ketoglutarate. Even at low concentrations, 2,4-D and MCPA were potent uncouplers
      of oxidative phosphorylation. Primary cultures of M. roosevelti liver cells may
      provide a useful tool for the evaluation of environmental contaminant effects. A
      review of regulations regarding permitted concentrations of these herbicides is
      needed.

PMID- 25996809
TI  - Comparative toxicity of rac- and S-tebuconazole to Daphnia magna.
AB  - Tebuconazole is a chiral triazole fungicide used as raceme in a variety of
      agricultural applications. Earlier studies showed that tebuconazole is toxic to
      many non-target aquatic organisms but relative data for tebuconazole enantiomers
      are lacking. Thus, goal of this study was to evaluate and compare the toxicity of
      rac- and S-tebuconazole with Daphnia magna at both acute and chronic levels
      according to Organization for Economic Cooperation and Development (OECD)
      guidelines 202 and 211 respectively, to provide some guidelines for optimizing
      chiral pesticides application and management. The exposure concentrations were
      0.1, 0.5, 1, 2, 4, 8, 10 mg L(-1) for both rac- and S-tebuconazole and their 48-h
      EC(50) values to D. magna were 3.53 (3.32-3.78) and 2.74 (2.33-3.10) mg L(-1)
      respectively, indicating that these both are medium toxic to D. magna with no
      significant toxicity difference at acute level. In chronic test, <24-h old D.
      magna were exposed to 0.01, 0.05, 0.10, 0.20, and 0.40 mg L(-1) of rac- and S
      tebuconazole with one blank and one solvent control for 21 days according to OECD
      guideline 211. Four developmental (molting rate, days to the 1st and 3rd brood,
      and body length) and five reproductive (size of the 1st and 3rd brood, number of
      broods, and number of neonates) parameters for each D. magna were determined.
      Results showed that both rac- and S-tebuconazole significantly reduced the
      reproduction and impacted the development of D. magna at concentrations of 0.05
      mg L(-1) or higher. Furthermore, S-tebuconazole was more toxic than raceme, and
      the difference between effects on the same parameters induced by rac- and S
      tebuconazole was statistically significant. These results demonstrated that the
      chronic toxicity of S-tebuconazole might be underestimated in general use, and
      further studies should focus more on the biological behaviors of enantiomers and
      not just the raceme of tebuconazole and other chiral pesticides in the
      environment.

PMID- 25996810
TI  - Effect of wheat and rice straw biochars on pyrazosulfuron-ethyl sorption and
      persistence in a sandy loam soil.
AB  - The objective of this research was to investigate the effect of wheat and rice
      biochars on pyrazosulfuron-ethyl sorption in a sandy loam soil. Pyrazosulfuron
      ethyl was poorly sorbed in the soil (3.5-8.6%) but biochar amendment increased
      the herbicide adsorption, and the effect varied with the nature of the feedstock
      and pyrolysis temperature. Biochars prepared at 600 degrees C were more effective
      in adsorbing pyrazosulfuron-ethyl than biochars prepared at 400 degrees C. Rice
      biochars were better than wheat biochars, and higher herbicide adsorption was
      attributed to the biochar surface area/porosity. The Freundlich constant 1/n
      suggested nonlinear isotherms, and nonlinearlity increased with increase in the
      level of biochar amendment. Desorption results suggested sorption of
      pyrazosulfuron-ethyl was partially irreversible, and the irreversibility
      increased with increase in the level of biochar. Both sorption and desorption of
      pyrazosulfuron-ethyl correlated well with the content of biochars. The free
      energy change (DeltaG) indicated that the pyrazosulfuron-ethyl sorption process
      was exothermic, spontaneous and physical in nature. Persistence studies indicated
      that biochar (0.5%) amendment did not have significant effect on herbicide
      degradation, and its half-life values in the control, 0.5% WBC600- and RBC600
      amended rice planted soils were 7, 8.6, and 10.4 days, respectively.

PMID- 25996811
TI  - Sorption-desorption of imidacloprid onto a lacustrine Egyptian soil and its clay
      and humic acid fractions.
AB  - Sorption-desorption of the insecticide imidacloprid 1-[(6-chloro-3-pyridinyl)
      methyl]-N-nitro-2-imidazolidinimine onto a lacustrine sandy clay loam Egyptian
      soil and its clay and humic acid (HA) fractions was investigated in 24-h batch
      equilibrium experiments. Imidacloprid (IMDA) sorption-desorption isotherms onto
      the three sorbents were found to belong to a non-linear L-type and were best
      described by the Freundlich model. The value of the IMDA adsorption distribution
      coefficient, Kd(ads), varied according to its initial concentration and was
      ranged 40-84 for HA, 14-58 for clay and 1.85-4.15 for bulk soil. Freundlich
      sorption coefficient, Kf(ads), values were 63.0, 39.7 and 4.0 for HA, clay and
      bulk soil, respectively. The normalized soil Koc value for imidacloprid sorption
      was ~800 indicating its slight mobility in soils. Nonlinear sorption isotherms
      were indicated by 1/n(ads) values <1 for all sorbents. Values of the hysteresis
      index (H) were <1, indicating the irreversibility of imidacloprid sorption
      process with all tested sorbents. Gibbs free energy (DeltaG) values indicated a
      spontaneous and physicosorption process for IMDA and a more favorable sorption to
      HA than clay and soil. In conclusion, although the humic acid fraction showed the
      highest capacity and affinity for imidacloprid sorption, the clay fraction
      contributed to approximately 95% of soil-sorbed insecticide. Clay and humic acid
      fractions were found to be the major two factors controlling IMDA sorption in
      soils. The slight mobility of IMDA in soils and the hysteresis phenomenon
      associated with the irreversibility of its sorption onto, mainly, clay and
      organic matter of soils make its leachability unlikely to occur.

PMID- 25996812
TI  - Inhibition kinetics of acid and alkaline phosphatases by atrazine and methomyl
      pesticides.
AB  - The main objective of this work was to investigate the kinetic characteristics of
      acid and alkaline phosphatases isolated from different sources and to study the
      effects of the herbicide atrazine and insecticide methomyl on the activity and
      kinetic properties of the enzymes. Acid phosphatase (ACP) was isolated from the
      tomato plant (Solanum lycopersicum L. var. lycopersicum); alkaline phosphatase
      (ALP) was isolated from two sources, including mature earthworms (Aporrectodea
      caliginosa) and larvae of the Egyptian cotton leafworm (Spodoptera littoralis).
      The specific activities of the enzymes were 33.31, 5.56 and 0.72 mmol substrate
      hydrolyzed per minute per milligram protein for plant ACP, earthworms ALP and
      cotton leafworm ALP, respectively. The inhibition kinetics indicated that
      atrazine and methomyl caused competitive-non-competitive inhibition of the
      enzymes. The relationships between estimates of K(m) and V(max) calculated from
      the Michaelis-Menten equation have been explored. The extent of the inhibition
      was different, as estimated by the values of the inhibition constant Ki that were
      found to be 3.34 * 10(-3), 1.12 * 10(-2) and 1.07 * 10(-2) mM for plant ACP,
      earthworms ALP and cotton leafworm ALP, respectively, with methomyl. In the case
      of atrazine, K(i) were found to be 8.99 * 10(-3), 3.55 * 10(-2) and 1.36 * 10(-2)
      mM for plant ACP, earthworms ALP and cotton leafworm ALP, respectively.

PMID- 25996813
TI  - Kinetics and isotherm analysis of 2,4-dichlorophenoxyl acetic acid adsorption
      onto soil components under oxic and anoxic conditions.
AB  - 2,4-dichlorophenoxyl acetic acid (2,4-D, pKa = 2.8) is used extensively as a
      herbicide in agricultural practices. Its sorption behavior on both untreated and
      soils treated to significantly remove specific components (organic and iron and
      manganese [Fe-Mn] oxides and hydroxides phases) was investigated under oxic and
      anoxic conditions. The chemical and structural heterogeneity of the soil
      components were characterized by elemental analysis and X-ray diffraction (XRD).
      The coexistence of the various components seems to either mask sorption sites on
      the untreated soil surfaces or inhibit interlayer diffusion of 2,4-D. All
      sorption data conform to the Freundlich description and a pseudo-second-order
      kinetic model. There was a strong positive correlation between sorption capacity
      K(d), and surface area (r(2) <= 0.704), but a negative correlation was uncovered
      with both pH and organic carbon (r(2) <= -0.860). The results indicate that 2,4-D
      is preferably sorbed under oxic rather than anoxic conditions and it is greater
      on soils containing a high Fe content. There was incomplete 2,4-D sorption
      reversibility, with desorption occurring more rapidly under anoxic conditions.
      The study suggests that stimulation of Fe III reduction could be used for the
      bioremediation of a 2,4-D-contaminated site.

PMID- 25996814
TI  - Degradation of alachlor using an enhanced sono-Fenton process with efficient
      Fenton's reagent dosages.
AB  - In this study, an enhanced sono-Fenton process for the degradation of alachlor is
      presented. At high ultrasonic power, low pH, and in the presence of adequate
      Fenton's reagent dosages, alachlor degradation can reach nearly 100%. The
      toxicity of treated alachlor wastewater, which was measured by changes in cell
      viability, slightly decreased after the Fenton or ultrasound/H2O2 process and
      significantly decreased after the enhanced sono-Fenton process. A satisfactory
      relationship was observed between the total organic carbon removal and cell
      viability increment, indicating that alachlor mineralization is a key step in
      reducing the toxicity of the solution. The formation of alachlor degradation
      byproducts was observed during the oxidation process, in which the first step was
      the substitution of a chloride by a hydroxyl group. In conclusion, the enhanced
      sono-Fenton process was effective in the degradation and detoxification of
      alachlor within a short reaction time. Thus, the treated wastewater can then be
      passed through a biological treatment unit for further treatment. 

PMID- 25996815
TI  - Method validation for control determination of mercury in fresh fish and shrimp
      samples by solid sampling thermal decomposition/amalgamation atomic absorption
      spectrometry.
AB  - A method for the determination of total mercury in fresh fish and shrimp samples
      by solid sampling thermal decomposition/amalgamation atomic absorption
      spectrometry (TDA AAS) has been validated following international foodstuff
      protocols in order to fulfill the Brazilian National Residue Control Plan. The
      experimental parameters have been previously studied and optimized according to
      specific legislation on validation and inorganic contaminants in foodstuff.
      Linearity, sensitivity, specificity, detection and quantification limits,
      precision (repeatability and within-laboratory reproducibility), robustness as
      well as accuracy of the method have been evaluated. Linearity of response was
      satisfactory for the two range concentrations available on the TDA AAS equipment,
      between approximately 25.0 and 200.0 MUg kg(-1) (square regression) and 250.0 and
      2000.0 MUg kg(-1) (linear regression) of mercury. The residues for both ranges
      were homoscedastic and independent, with normal distribution. Correlation
      coefficients obtained for these ranges were higher than 0.995. Limits of
      quantification (LOQ) and of detection of the method (LDM), based on signal
      standard deviation (SD) for a low-in-mercury sample, were 3.0 and 1.0 MUg kg(-1),
      respectively. Repeatability of the method was better than 4%. Within-laboratory
      reproducibility achieved a relative SD better than 6%. Robustness of the current
      method was evaluated and pointed sample mass as a significant factor. Accuracy
      (assessed as the analyte recovery) was calculated on basis of the repeatability,
      and ranged from 89% to 99%. The obtained results showed the suitability of the
      present method for direct mercury measurement in fresh fish and shrimp samples
      and the importance of monitoring the analysis conditions for food control
      purposes. Additionally, the competence of this method was recognized by
      accreditation under the standard ISO/IEC 17025.

PMID- 25996816
TI  - Elevating concentrations of capsaicin and dihydrocapsaicin in hot peppers using
      recycled waste.
AB  - Five Capsicum accessions (PI 435916 and PI 438614 from Capsicum chinense; PI
      370004 and Grif 9354 from C. baccatum and PI 438649 from C. annuum) were selected
      from the U.S. Department of Agriculture-Agricultural Research Service Capsicum
      germplasm collection to study the impact of four soil management practices: yard
      waste (YW), sewage sludge (SS), chicken manure (CM) and no-mulch (NM) bare soil
      on fruit concentrations of capsaicin and dihydrocapsaicin, yield, plant size and
      mature fruit characteristics (fruit weight, length, width, and wall-thickness) of
      plants grown under these practices. Regardless of soil treatments, PI 438614 and
      PI 435916 contained the greatest concentrations of total capsaicinoids (capsaicin
      and dihydrocapsaicin). Fruits of plants grown in soil mixed with SS contained the
      greatest concentrations of total capsaicinoids. Fruits of plants grown in SS or
      CM contained the greatest fruit weight. PI 438649 produced the greatest fruit
      weight, length and wall-thickness. The total marketable yield expressed as weight
      of fruit plants was significantly higher in soils mixed with SS and CM compared
      to those mixed with YW and NM soils. 

PMID- 25996817
TI  - Conceptual decomposition of complex health care interventions for evidence
      synthesis: a literature review.
AB  - RATIONALE, AIMS AND OBJECTIVES: The clarity of pivotal concepts is an important
      prerequisite for the development, evaluation and exchange of scientific ideas.
      The term 'complex intervention' is increasingly used in the health care
      literature, although it often remains unclear what is actually meant by this
      concept. Therefore, our aim was to analyse the literature regarding definitions
      of the terms 'complex intervention' and 'components' of such interventions.
      METHOD: To identify the methodological publications, systematic and snowballing
      techniques were combined for the literature search. Relevant units of meaning
      were extracted from 68 included publications. Afterwards, we deduced categories
      and related frequencies by inductive and quantitative content analysis
      techniques. RESULTS: Several types of complexity were distinguished in the
      literature. Most authors viewed complex interventions as multicomponent
      interventions that are characterized by interactions between the components
      themselves, with the context or as systemic interventions. Components of complex
      interventions were described in the publications as having the potential to
      causally influence outcomes, thus being essential for achieving an effect. Other
      definitions and inconsistencies among the definitions are highlighted and
      discussed. CONCLUSIONS: From our synthesis, we derived definitions of the central
      health care-related concepts 'complex intervention' and 'components' of an
      intervention. Although we found numerous diverse definitions, they could be
      reduced to a defined number of core characteristics. These characteristics may
      facilitate communication regarding complex interventions and enable the deduction
      of methodological approaches for evidence synthesis.

PMID- 25996818
TI  - Magnitude Differences in Bioactive Compounds, Chemical Functional Groups, Fatty
      Acid Profiles, Nutrient Degradation and Digestion, Molecular Structure, and
      Metabolic Characteristics of Protein in Newly Developed Yellow-Seeded and Black
      Seeded Canola Lines.
AB  - Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have
      been developed with chemical and structural alteration through modern breeding
      technology. However, no systematic study was found on the bioactive compounds,
      chemical functional groups, fatty acid profiles, inherent structure, nutrient
      degradation and absorption, or metabolic characteristics between the newly
      developed yellow- and black-seeded canola lines. This study aimed to
      systematically characterize chemical, structural, and nutritional features in
      these canola lines. The parameters accessed include bioactive compounds and
      antinutrition factors, chemical functional groups, detailed chemical and nutrient
      profiles, energy value, nutrient fractions, protein structure, degradation
      kinetics, intestinal digestion, true intestinal protein supply, and feed milk
      value. The results showed that the CS-Y line was lower (P <= 0.05) in neutral
      detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM),
      lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid
      detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no
      difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9)
      which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The
      glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl,
      3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 MUmol/g) between the CS-Y
      and CS-B lines. For bioactive compounds, total polyphenols tended to be different
      (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed
      tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was
      portioned into five subfractions, significant differences were found in PA, PB1
      (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein
      degradation and supply to small intestine differed between two new lines. In
      terms of protein structure spectral profile, there were no significant
      differences in functional groups of amides I and II, alpha helix, and beta-sheet
      structure as well as their ratio between the two new lines, indicating no
      difference in protein structure makeup and conformation between the two lines. In
      terms of energy values, there were significant differences in total digestible
      nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM),
      and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B
      lines. For in situ rumen degradation kinetics, the two lines differed in soluble
      fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590
      g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but
      no difference in degradation rate. CS-Y had higher digestibility of rumen bypass
      protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling
      nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171
      g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower
      in the CS-Y line, but there were no differences in total truly digested protein
      in small intestine (DVE) and feed milk value (FMV) between the two lines. In
      conclusion, the new yellow line had different nutritional, chemical, and
      structural features compared to the black line. CS-Y provided better nutrient
      utilization and availability. 

PMID- 25996821
TI  - Radical polymerization of 2,3-dimethyl-1,3-butadiene in coordination
      nanochannels.
AB  - Radical polymerization of unpolymerizable sterically hindered butadiene was
      successfully performed in the nanochannels of porous coordination polymers
      because of the effective suppression of unfavourable termination reactions.
      Microstructures of the resulting polymer could also be tuned depending on the
      structure of the porous hosts. 

PMID- 25996822
TI  - Nutrient Excess and AMPK Downregulation in Incubated Skeletal Muscle and Muscle
      of Glucose Infused Rats.
AB  - We have previously shown that incubation for 1h with excess glucose or leucine
      causes insulin resistance in rat extensor digitorum longus (EDL) muscle by
      inhibiting AMP-activated protein kinase (AMPK). To examine the events that
      precede and follow these changes, studies were performed in rat EDL incubated
      with elevated levels of glucose or leucine for 30min-2h. Incubation in high
      glucose (25mM) or leucine (100MUM) significantly diminished AMPK activity by 50%
      within 30min, with further decreases occurring at 1 and 2h. The initial decrease
      in activity at 30min coincided with a significant increase in muscle glycogen.
      The subsequent decreases at 1h were accompanied by phosphorylation of alphaAMPK
      at Ser485/491, and at 2h by decreased SIRT1 expression and increased PP2A
      activity, all of which have previously been shown to diminish AMPK activity.
      Glucose infusion in vivo, which caused several fold increases in plasma glucose
      and insulin, produced similar changes but with different timing. Thus, the
      initial decrease in AMPK activity observed at 3h was associated with changes in
      Ser485/491 phosphorylation and SIRT1 expression and increased PP2A activity was a
      later event. These findings suggest that both ex vivo and in vivo, multiple
      factors contribute to fuel-induced decreases in AMPK activity in skeletal muscle
      and the insulin resistance that accompanies it. 

PMID- 25996826
TI  - Incidence of Medically-Attended Norovirus-Associated Acute Gastroenteritis in
      Four Veteran's Affairs Medical Center Populations in the United States, 2011
      2012.
AB  - An estimated 179 million acute gastroenteritis (AGE) illnesses occur annually in
      the United States. The role of noroviruses in hospital-related AGE has not been
      well-documented in the U. S. We estimated the population incidence of community-
      acquired outpatient and inpatient norovirus AGE encounters, as well as hospital
      acquired inpatient norovirus AGE among inpatients at four Veterans Affairs (VA)
      Medical Centers (VAMCs). Fifty (4%) of 1,160 stool specimens collected <=7 days
      from symptom onset tested positive for norovirus. During a one year period, the
      estimated incidence of outpatient, community- and hospital-acquired inpatient
      norovirus AGE was 188 cases, 11 cases, and 54 cases/ 100,000 patients,
      respectively. This study demonstrates the incidence of outpatient and community-
      and hospital-acquired inpatient norovirus AGE among the VA population seeking
      care at these four VAMCs. 

PMID- 25996827
TI  - Severe gastrointestinal toxicity with administration of trametinib in combination
      with dabrafenib and ipilimumab.

PMID- 25996828
TI  - MRI findings of young male soldiers with atraumatic anterior knee pain.
AB  - The purpose of this study is to investigate abnormal magnetic resonance image
      (MRI) findings of young active males with atraumatic anterior knee pain (AKP).
      Targeting young male soldiers, we prospectively gathered and analyzed 157 knee
      MRIs from patients with atraumatic AKP (AKP group) and 53 knee MRIs from patients
      without knee pain (control group). Abnormalities of the patellofemoral (PF) joint
      and extensor mechanism on MRI were more common in the AKP group than the control
      group (48% vs 13%, P < 0.001). The overall prevalence of medial plica (34% vs
      13%, P = 0.004) and the prevalence of the thick medial plica (9% vs 0%, P =
      0.023) were considerably higher in the AKP group. The cartilaginous sulcus angle
      in the AKP group without abnormalities on MRI was significantly higher than both
      the AKP group with abnormalities and the control group (145 degrees  vs 141
      degrees  vs 142 degrees , respectively, P = 0.001). Our results suggest that
      careful assessment of young, active males with atraumatic AKP is warranted
      regarding PF joint abnormalities, particularly the presence of medial plica
      and/or subtle abnormalities of the articular geometry. The results from the
      present study could be used for the management of patients with AKP. 

PMID- 25996829
TI  - Investigating fungal outbreaks in the 21st century.

PMID- 25996831
TI  - The use and value of procalcitonin in solid organ transplantation.
AB  - Procalcitonin (PCT) has been increasingly used as a biomarker of bacterial
      infection and as a tool to guide antimicrobial therapy, especially in lower
      respiratory tract and bloodstream infections. Despite its increased use, data in
      patients with solid organ transplants are limited. Even without the presence of
      infection, PCT increases as a result of surgical procedures during
      transplantation, implantation of devices, and use of induction immunosuppressive
      therapy. The risk of infection is also higher in solid organ transplant
      recipients when compared to the general population. Monitoring PCT in the early
      post-transplant period seems to be a promising method for early detection of
      infectious complications. It has been shown that elevated PCT levels after one wk
      of transplantation are correlated with infectious complications. PCT may be a
      useful adjunctive biomarker that may improve early identification and guide
      appropriate treatment of infection or rejection, with the potential to further
      improve clinical outcomes. The use of serial PCT measurements may be more
      reliable than single values. It is important to recognize which factors may lead
      to PCT increases in the post-transplantation period, which in turn will help
      understand the kinetics and utility of this biomarker in this important patient
      population.

PMID- 25996830
TI  - Myopathic lamin mutations cause reductive stress and activate the nrf2/keap-1
      pathway.
AB  - Mutations in the human LMNA gene cause muscular dystrophy by mechanisms that are
      incompletely understood. The LMNA gene encodes A-type lamins, intermediate
      filaments that form a network underlying the inner nuclear membrane, providing
      structural support for the nucleus and organizing the genome. To better
      understand the pathogenesis caused by mutant lamins, we performed a structural
      and functional analysis on LMNA missense mutations identified in muscular
      dystrophy patients. These mutations perturb the tertiary structure of the
      conserved A-type lamin Ig-fold domain. To identify the effects of these
      structural perturbations on lamin function, we modeled these mutations in
      Drosophila Lamin C and expressed the mutant lamins in muscle. We found that the
      structural perturbations had minimal dominant effects on nuclear stiffness,
      suggesting that the muscle pathology was not accompanied by major structural
      disruption of the peripheral nuclear lamina. However, subtle alterations in the
      lamina network and subnuclear reorganization of lamins remain possible. Affected
      muscles had cytoplasmic aggregation of lamins and additional nuclear envelope
      proteins. Transcription profiling revealed upregulation of many Nrf2 target
      genes. Nrf2 is normally sequestered in the cytoplasm by Keap-1. Under oxidative
      stress Nrf2 dissociates from Keap-1, translocates into the nucleus, and activates
      gene expression. Unexpectedly, biochemical analyses revealed high levels of
      reducing agents, indicative of reductive stress. The accumulation of cytoplasmic
      lamin aggregates correlated with elevated levels of the autophagy adaptor
      p62/SQSTM1, which also binds Keap-1, abrogating Nrf2 cytoplasmic sequestration,
      allowing Nrf2 nuclear translocation and target gene activation. Elevated
      p62/SQSTM1 and nuclear enrichment of Nrf2 were identified in muscle biopsies from
      the corresponding muscular dystrophy patients, validating the disease relevance
      of our Drosophila model. Thus, novel connections were made between mutant lamins
      and the Nrf2 signaling pathway, suggesting new avenues of therapeutic
      intervention that include regulation of protein folding and metabolism, as well
      as maintenance of redox homoeostasis. 

PMID- 25996832
TI  - Satisfaction with youth mental health services: further scale development and
      findings from headspace - Australia's National Youth Mental Health Foundation.
AB  - AIMS: This study aimed to determine the psychometric properties of the headspace
      youth (mental health) service satisfaction scale (YSSS), a 14-item purpose
      designed scale for use with adolescents and young adults attending headspace
      centres, and to examine the level of satisfaction with headspace centre services
      and the client characteristics that predict this. METHODS: There were 21 354
      eligible headspace clients who had received more than one service over the 12
      month data collection period during 2013-2014, and 12 436 (58%) completed a
      satisfaction scale. headspace clients could optionally self-complete the
      satisfaction scale at the beginning of visits 2, 5, 10 and 15. Clients'
      demographic and clinical characteristics were also recorded. RESULTS: Factor
      analysis identified a four-factor solution for the scale and internal consistency
      of the subscales was acceptable to excellent. Satisfaction with headspace was
      high and increased over time for those who completed the scale multiple times.
      Several demographic and clinical characteristics predicted the likelihood of
      completion and level of satisfaction, with younger age shown to be a persistent
      predictor of lower satisfaction. CONCLUSIONS: Client satisfaction with headspace
      is high and increases with ongoing engagement. Development of the headspace YSSS
      contributes a new client satisfaction scale with tested psychometric properties
      for adolescents and young adults engaged in mental health services, providing an
      essential tool for youth mental health services to routinely evaluate the
      experiences of young people accessing their services.

PMID- 25996833
TI  - Circumscribed palmoplantar hypokeratosis in a barber: Successful treatment using
      cryotherapy.

PMID- 25996834
TI  - In-vivo bioavailability and lymphatic uptake evaluation of lipid nanoparticulates
      of darunavir.
AB  - Darunavir is effective against wild-type and PI-resistant HIV, and has an oral
      bioavailability of 37%. It needs to be combined with ritonavir, which increases
      the bioavailability to 82%. The aim of this study was to evaluate the in-vivo
      efficacy of the darunavir-SLN and demonstrate lymphatic transport as a
      contributing pathway in increasing the drug bioavailability. The SLN was prepared
      by hot-homogenization technique using GMS as lipid. In-vitro drug release from
      SLN at the 12th hour was retarded (80.6%) compared to marketed tablet (92.6%). Ex
      vivo apparent permeability of the freeze-dried SLN across everted rat intestine
      was 24 * 10-6 at 37  degrees C and 5.6 * 10-6 at 4  degrees C. The presence of
      endocytic process inhibitors like chlorpromazine and nystatin reduced it to 18.8
      * 10-6 and 20.2 * 10-6, respectively, which established involvement of endocytic
      mechanism in the uptake of SLN. In-vivo pharmacokinetic studies on rats
      demonstrated increase in the AUC of SLN (26) as compared to that of marketed
      tablet (13.22), while the presence of lymphatic uptake inhibitor cycloheximide
      lowered the AUC of SLN to 17.19 which further led credence to the involvement of
      lymphatic uptake behind improved bioavailability. The detection of darunavir in
      the lymphatic fluid of the rats administered with darunavir-SLN further
      reinforced the conclusion of SLN being taken up by the lymphatic system.

PMID- 25996835
TI  - Caregivers' Illness Perceptions Contribute to Quality of Life in Head and Neck
      Cancer Patients at Diagnosis.
AB  - This study investigated the contribution of patient and caregiver illness
      perceptions to the quality of life of head and neck cancer (HNC) patients. Ninety
      eight patients and their caregivers (n = 80) completed questionnaires at
      diagnosis. Caregivers' illness perceptions were significantly more negative than
      patients with respect to consequences, timeline, treatment, concern, and the
      emotional impact of HNC. The interaction between some patient and caregiver
      illness perceptions explained additional variance in patient quality of life,
      above and beyond patients' own illness perceptions. These findings suggest that
      caregivers should be included in psychological interventions to improve HNC
      patient quality of life. 

PMID- 25996837
TI  - Use of Clotted Human Plasma and Aprotinin in Skin Tissue Engineering: A Novel
      Approach to Engineering Composite Skin on a Porous Scaffold.
AB  - Tissue-engineered composite skin is a promising therapy for the treatment of
      chronic and acute wounds, including burns. Providing the wound bed with a dermal
      scaffold populated by autologous dermal and epidermal cellular components can
      further entice host cell infiltration and vascularization to achieve permanent
      wound closure in a single stage. However, the high porosity and the lack of a
      supportive basement membrane in most commercially available dermal scaffolds
      hinders organized keratinocyte proliferation and stratification in vitro and may
      delay re-epithelization in vivo. The objective of this study was to develop a
      method to enable the in vitro production of a human skin equivalent (HSE) that
      included a porous scaffold and dermal and epidermal cells expanded ex vivo, with
      the potential to be used for definitive treatment of skin defects in a single
      procedure. A collagen-glycosaminoglycan dermal scaffold (Integra((r))) was
      populated with adult fibroblasts. A near-normal skin architecture was achieved by
      the addition of coagulated human plasma to the fibroblast-populated scaffold
      before seeding cultured keratinocytes. This resulted in reducing scaffold pore
      size and improving contact surfaces. Skin architecture and basement membrane
      formation was further improved by the addition of aprotinin (a serine protease
      inhibitor) to the culture media to inhibit premature clot digestion. Histological
      assessment of the novel HSE revealed expression of keratin 14 and keratin 10
      similar to native skin, with a multilayered neoepidermis morphologically
      comparable to human skin. Furthermore, deposition of collagen IV and laminin-511
      were detected by immunofluorescence, indicating the formation of a continuous
      basement membrane at the dermal-epidermal junction. The proposed method was
      efficient in producing an in vitro near native HSE using the chosen off-the-shelf
      porous scaffold (Integra). The same principles and promising outcomes should be
      applicable to other biodegradable porous scaffolds, combined with autologous
      cells, for use in wound treatment. 

PMID- 25996836
TI  - Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible
      Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli.
AB  - Bacterial mechano-sensitive (MS) channels reside in the inner membrane and are
      considered to act as emergency valves whose role is to lower cell turgor when
      bacteria enter hypo-osmotic environments. However, there is emerging evidence
      that members of the Mechano-sensitive channel Small (MscS) family play additional
      roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C
      terminal region that changes its shape upon activation and inactivation of the
      channel. Our pull-down and co-sedimentation assays show that this domain
      interacts with FtsZ, a bacterial tubulin-like protein. We identify point
      mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that
      bacteria expressing these mutants are compromised in growth on sublethal
      concentrations of beta-lactam antibiotics. Our results suggest that interaction
      between MscS and FtsZ could occur upon inactivation and/or opening of the channel
      and could be important for the bacterial cell response against sustained stress
      upon stationary phase and in the presence of beta-lactam antibiotics. 

PMID- 25996838
TI  - Persistence of immunity in healthy adults aged >= 50 years primed with a
      hepatitis B vaccine 3 years previously.
AB  - Hepatitis B vaccines do not generate protective immune responses in older adults
      as effectively as they do in children and young adults. Improved formulations of
      existing vaccines may have the potential to improve this. This study investigated
      the persistence of serum antibodies against hepatitis B surface antigens (anti
      HBs) 3.1-3.5 years following primary vaccination with 3 doses of HBvaxPRO(r) or
      Engerix BTM in healthy adults aged >= 50 years who were further challenged with 1
      dose of recombinant hepatitis B antigen. This was an open-label extension study.
      Individuals (N = 204) with a mean (standard deviation) age at enrollment of 63.7
      (7.0) years receiving HBvaxPRO(r) or Engerix BTM in a randomized, double-blind
      primary study were challenged with 1 dose of HBvaxPRO(r) (10 MUg). Anti-HBs were
      measured pre- and 30 days post-challenge. 45.5% (34.8, 56.4 [95% CI]) of
      individuals who received HBvaxPRO(r) in the per protocol set (PPS) had anti-HBs
      titers >= 10 mIU/mL pre-challenge and 85.2% (76.1, 91.9) 1-month post-challenge.
      In those who received Engerix BTM in the primary vaccination series, the results
      were 58.8% (48.6, 68.5) and 88.3% (80.5, 93.8), respectively. The challenge dose
      of HBvaxPRO(r) was generally well tolerated. Subjects aged >= 50 years receiving
      a challenge dose of HBvaxPRO(r) demonstrated immune memory against hepatitis B 3
      years after a 3-dose primary. The safety profile of this challenge dose of
      HBvaxPRO(r) was consistent with the well-established safety profile of the
      vaccine HBvaxPRO(r).

PMID- 25996840
TI  - Age-Related Cortical Thickness Reduction in Non-Demented Down's Syndrome
      Subjects.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate the
      characteristic pattern of age-related cortical thinning in patients with Down
      Syndrome (DS), as assessed by MRI and automatic cortical thickness measurements.
      METHODS: Ninety-one non-demented subjects with DS (range 11-53 years) were
      examined using a 1.5 T scanner. MRI-based quantification of cortical thickness
      was performed using FreeSurfer software package., The Pearson product-moment
      correlation coefficient between age and mean cortical thickness was evaluated for
      all subjects participating in the study. RESULTS: A significant negative
      correlation between cortical thickness and age was found bilaterally in the
      frontal, temporal, parietal and cingulate gyrus. Specific investigation of
      cerebral lobes showed a more evident involvement of the frontal one, compared to
      others. Moreover, the age related reduction of cortical thickness appeared to be
      more significant and rapid in patients between 20 and 30 years of age.
      CONCLUSIONS: Our findings showed that Down Syndrome subjects are affected by a
      diffuse cortical thinning. The involvement of cortical structures can be observed
      at an earlier age than previous studies have reported.

PMID- 25996839
TI  - Characterization of the Newly Isolated Lytic Bacteriophages KTN6 and KT28 and
      Their Efficacy against Pseudomonas aeruginosa Biofilm.
AB  - We here describe two novel lytic phages, KT28 and KTN6, infecting Pseudomonas
      aeruginosa, isolated from a sewage sample from an irrigated field near Wroclaw,
      in Poland. Both viruses show characteristic features of Pbunalikevirus genus
      within the Myoviridae family with respect to shape and size of head/tail, as well
      as LPS host receptor recognition. Genome analysis confirmed the similarity to
      other PB1-related phages, ranging between 48 and 96%. Pseudomonas phage KT28 has
      a genome size of 66,381 bp and KTN6 of 65,994 bp. The latent period, burst size,
      stability and host range was determined for both viruses under standard
      laboratory conditions. Biofilm eradication efficacy was tested on peg-lid plate
      assay and PET membrane surface. Significant reduction of colony forming units was
      observed (70-90%) in 24 h to 72 h old Pseudomonas aeruginosa PAO1 biofilm
      cultures for both phages. Furthermore, a pyocyanin and pyoverdin reduction tests
      reveal that tested phages lowers the amount of both secreted dyes in 48-72 h old
      biofilms. Diffusion and goniometry experiments revealed the increase of diffusion
      rate through the biofilm matrix after phage application. These characteristics
      indicate these phages could be used to prevent Pseudomonas aeruginosa infections
      and biofilm formation. It was also shown, that PB1-related phage treatment of
      biofilm caused the emergence of stable phage-resistant mutants growing as small
      colony variants. 

PMID- 25996841
TI  - Human UDP-Glucuronosyltransferases: Effects of altered expression in breast and
      pancreatic cancer cell lines.
AB  - Increased aerobic glycolysis and de novo lipid biosynthesis are common
      characteristics of invasive cancers. UDP-glucuronosyltransferases (UGTs) are
      phase II drug metabolizing enzymes that in normal cells possess the ability to
      glucuronidate these lipids and speed their excretion; however, de-regulation of
      these enzymes in cancer cells can lead to an accumulation of bioactive lipids,
      which further fuels cancer progression. We hypothesize that UGT2B isoform
      expression is down-regulated in cancer cells and that exogenous re-introduction
      of these enzymes will reduce lipid content, change the cellular phenotype, and
      inhibit cancer cell proliferation. In this study, steady-state mRNA levels of UGT
      isoforms from the 2B family were measured using qPCR in 4 breast cancer and 5
      pancreatic cancer cell lines. Expression plasmids for UGT2B isoforms known to
      glucuronidate cellular lipids, UGT2B4, 2B7, and 2B15 were transfected into MCF-7
      and Panc-1 cells, and the cytotoxic effects of these enzymes were analyzed using
      trypan blue exclusion, annexin V/PI staining, TUNEL assays, and caspase-3
      immunohistochemistry. There was a significant decrease in cell proliferation and
      a significant increase in the number of dead cells after transfection with each
      of the 3 UGT isoforms in both cell lines. Cellular lipids were also found to be
      significantly decreased after transfection. The results presented here support
      our hypothesis and emphasize the important role UGTs can play in cellular
      proliferation and lipid homeostasis. Evaluating the effect of UGT expression on
      the lipid levels in cancer cell lines can be relevant to understanding the
      complex regulation of cancer cells, identifying the roles of UGTs as "lipid
      controllers" in cellular homeostasis, and illustrating their suitability as
      targets for future clinical therapy development. 

PMID- 25996842
TI  - Endovascular repair of ruptured abdominal aortic aneurysms with the endurant
      stent-graft: a combined experience from three centers.
AB  - BACKGROUND: Endovascular repair of ruptured abdominal aortic aneurysms (RAAAs)
      has been previously reported to reduce mortality rates compared to open repair.
      Newer stent-grafts may provide even better results with applicability in a larger
      number of patients. We present our experience with the Medtronic Endurant
      endograft over a three-year period. METHODS: Consecutive cases of RAAAs which
      have been managed with the Endurant stent-graft were recruited from three centers
      and were analyzed retrospectively. Twenty-three patients (22 males; mean age 74+/
      9 years) were treated between June 2010 and May 2013. RESULTS: The technical
      success rate was 100% with no intraoperative endoleaks. Thirty-day mortality was
      13% (3/23 patients). Two patients required prolonged hospitalization and
      mechanical ventilation. For the remaining 18 patients, the average
      hospitalization length was 5.5 days. Two major risk factors were found to be
      significantly associated with increased mortality: low systolic blood pressure on
      arrival at the hospital (63+/-6 vs. 99+/-22; P=0.01), and post-operative
      development of an abdominal compartment syndrome (Relative Risk - RR=13.3, 95%
      confidence interval - CI: 1.6-106; P=0.03). Other important clinical variables
      which did not significantly affect mortality included age (mean age 83+/-9 years
      in those who died vs. 73+/-9 years in the survivors; P=0.09), type of graft
      (bifurcated vs. aorto-uni-iliac; RR=2.2, 95% CI: 0.3-15; P=0.4), aneurysm
      diameter (11+/-4 cm vs. 9+/-2 cm; P=0.28), and proximal neck angulation (68+/-14
      vs. 57+/-26 degrees; P=0.5). A proximal neck angulation >75 degrees  was not
      associated with a higher mortality rate (RR=1.33, 95% CI: 0.22-7.8; P=1).
      CONCLUSIONS: Endovascular repair of RAAAs resulted in high technical success and
      low mortality rates in this series of patients treated with the Endurant stent
      graft. Hypotension on arrival to the hospital and development of an abdominal
      compartment syndrome were predictive of increased risk of death. Patient age,
      aneurysm diameter and graft configuration did not negatively impact survival. Non
      compliance with the device instructions for use (IFU) did not adversely affect
      results in this small patient series. Larger studies are needed to confirm our
      results.

PMID- 25996843
TI  - Physician-initiated prospective Italian Registry of carotid stenting with the C
      Guard mesh-stent: the IRON-Guard registry. Rationale and design.
AB  - According to the World Health Organization, every year, 5 million peoples die for
      stroke and another 5 million are permanently disabled. Although there are many
      causes of acute stroke, a common treatable cause of acute stroke is atheromatous
      narrowing at the carotid bifurcation. Carotid endarterectomy is still the
      standard of car, even if carotid artery stenting (CAS) has become an effective,
      less invasive alterantive. Unfortunately, CAS procedure is not yet perfect;
      regardless the use of an embolic protection device (EPD), percutaneous treatment
      has been correlated with a risk of cerebral ischemic events related to distal
      embolization. The objective of the IRON-Guard Registry is to evaluate the
      clinical outcome of treatment by means of stenting with the C-Guard (InspireMD,
      Boston, MA, USA) in subjects requiring CAS due to significant extracranial
      carotid artery stenosis with a physician-initiated, Italian, prospective,
      multicenter, single-arm study. A total of 200 enrolled subjects divided over
      different centers are planned to be enrolled. CAS will performed by implanting of
      C-Guard stent. Procedure will be performed according to the physician's standard
      of care. Standard procedures will be followed based on the Instructions for Use,
      for the C-Guard device of Inspire. The primary endpoint of this study is the 30
      day rate of major adverse events (MAE), defined as the cumulative incidence of
      any periprocedural (<=30 days postprocedure) death, stroke or myocardial
      infarction. Secondary endpoints are rate of late ipsilateral stroke (31 through
      365 days), system technical success, device malfunctions, major adverse events
      (MAEs), serious device-related and procedure-related adverse events, target
      lesion revascularization, and in-stent restenosis rates. 

PMID- 25996844
TI  - Head-Jolting Nystagmus: Occlusion of the Horizontal Semicircular Canal Induced by
      Vigorous Head Shaking.
AB  - IMPORTANCE: We report a new syndrome, which we are calling head-jolting
      nystagmus, that expands the differential diagnosis of head movement-induced
      paroxysmal vertigo. OBSERVATIONS: Two male patients (65 and 58 years old)
      described rotational vertigo after violent and brief (1- to 2-second)
      oscillations of the head (head jolting) that triggered intense horizontal
      nystagmus lasting 45 seconds. Accelerations of the head required to induce these
      episodes could only be achieved by the patients themselves. In case 1, the
      episodes gradually disappeared over a 6-year period. In case 2, magnetic
      resonance imaging (3-T) suggested a filling defect within the left horizontal
      semicircular canal. He underwent surgical canal plugging in March 2013 that
      resolved the symptoms. CONCLUSIONS AND RELEVANCE: We attribute head-jolting
      nystagmus to dislodged material within the horizontal semicircular canal and
      provide a mechanistic model to explain its origin.

PMID- 25996845
TI  - High- and Low-Frequency Decrement Contribution to Spectral Enhancement.
AB  - PURPOSE: The relative benefit of a single, flanking, high- or low-frequency
      decrement was assessed to better understand properties of spectral enhancement
      that may aid in algorithm design. METHOD: Detection thresholds were measured for
      intensity increments applied to a narrow target band of frequencies embedded in a
      broadband signal while 400-Hz-wide, 9- or 12-dB-deep intensity decrements were
      placed above, below, or on both sides of the target band. A mono condition with
      no decrements was used as a control. Eight participants with normal hearing and 8
      participants with hearing impairment took part in this experiment. RESULTS:
      Performance improved in the presence of decrements for both groups and was
      equivalent for both high- or low-frequency decrements. Comparison with
      individually measured auditory filters revealed that participants with normal
      hearing made use of energy cues available within these filters, whereas some
      participants with hearing impairment, despite improved increment detection,
      underutilized this information. CONCLUSION: Inclusion of a single, adjacent, high
      or low-frequency decrement improved increment detection but not to the same
      extent as when decrements flanked both sides.

PMID- 25996848
TI  - Association between salivary amylase (AMY1) gene copy numbers and insulin
      resistance in asymptomatic Korean men.
AB  - AIMS: Salivary amylase gene (AMY1) copy number variations (CNVs) correlate
      directly with salivary amylase activity and serum amylase levels. Previously,
      individuals with high AMY1 CNVs exhibited low postprandial glucose levels and
      postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may
      play a role in lowering the risk of insulin resistance. METHODS: We verified the
      relationship between AMY1 CNVs and homeostatic model assessment-insulin
      resistance (HOMA-IR) in a cohort of 1257 Korean men aged 20-65 years who visited
      two medical centres for regular health check-ups, and in subgroups of current
      smokers and regular alcohol drinkers. Individuals with fasting plasma glucose
      levels > 10.0 mmol/l, HbA1c >= 64 mmol/mol (8.0%) or who used oral hypoglycaemic
      agents or insulin were excluded. RESULTS: AMY1 CNVs correlated negatively with
      HOMA-IR even after adjusting for covariates (e.g. BMI, systolic blood pressure,
      triacylglycerol, alcohol consumption, smoking and physical activity). When the
      participants were divided according to current smoking and alcohol consumption
      habits, negative correlations between AMY1 CNVs and HOMA-IR were more evident
      among non-smokers and regular drinkers and were non-significant among smokers and
      non-regular drinkers. CONCLUSIONS: Low AMY1 CNVs correlated with high insulin
      resistance in asymptomatic Korean men, and such a relationship presented
      differently according to the status of smoking and alcohol consumption.

PMID- 25996847
TI  - Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia.
AB  - BACKGROUND: Neonatal encephalopathy following birth asphyxia is a major predictor
      of long-term neurological impairment. Therapeutic hypothermia is currently the
      standard of care to prevent brain injury in asphyxiated newborns but is not
      protective in all cases. More robust and versatile treatment options are needed.
      Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no
      systematic study examines the expression of angiogenesis-related markers
      following birth asphyxia in human newborns. OBJECTIVE: This study aimed to
      evaluate the expression of angiogenesis-related protein markers in asphyxiated
      newborns developing and not developing brain injury compared to healthy control
      newborns. DESIGN/METHODS: Twelve asphyxiated newborns treated with hypothermia
      were prospectively enrolled; six developed eventual brain injury and six did not.
      Four healthy control newborns were also included. We used Rules-Based Medicine
      multi-analyte profiling and protein array technologies to study the plasma
      concentration of 49 angiogenesis-related proteins. Mean protein concentrations
      were compared between each group of newborns. RESULTS: Compared to healthy
      newborns, asphyxiated newborns not developing brain injury showed up-regulation
      of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6
      phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3;
      this up-regulation was not evident in asphyxiated newborns eventually developing
      brain injury. Also, asphyxiated newborns developing brain injury showed a
      decreased expression of anti-angiogenic proteins, including insulin-growth factor
      binding proteins -1, -4, and -6, compared to healthy newborns. CONCLUSIONS: These
      findings suggest that angiogenesis pathways are dysregulated following birth
      asphyxia and are putatively involved in brain injury pathology and recovery.

PMID- 25996849
TI  - A Preliminary Investigation of Abnormal Personality Traits in MS Using the MCMI
      III.
AB  - Neuropsychiatric abnormalities are frequently reported in patients with multiple
      sclerosis (MS). Previous studies have investigated the neurotic aspects of
      psychopathology, and the importance of the personality structure underlying
      neurotic symptoms has only recently been reconsidered. The aim of our study was
      to investigate the frequency and type of personality profiles in MS using the
      Millon Clinical Multiaxial Inventory-III (MCMI-III). We evaluated 77 nondemented
      patients with MS using physical disability scales and self-report questionnaires
      focused on mood, fatigue, and personality. In our cohort study, we found a
      personality scale score greater than 85 in 62.3% of enrolled participants. In
      particular, high scores on the Histrionic and Narcissistic scales emerged,
      respectively, in 20.8% and 15.6% of the sample. The presence of moderate abnormal
      elevation scores in MCMI personality scales in MS does not seem to be influenced
      by age, the Expanded Disability Status Scale score, disease course, or disease
      duration. Our research study focused on the importance of identifying personality
      maladaptation in patients with MS. 

PMID- 25996852
TI  - The Pythagorean table of opposites, symbolic classification, and Aristotle.
AB  - ARGUMENT: At Metaphysics A 5 986a22-b2, Aristotle refers to a Pythagorean table,
      with two columns of paired opposites. I argue that 1) although Burkert and Zhmud
      have argued otherwise, there is sufficient textual evidence to indicate that the
      table, or one much like it, is indeed of Pythagorean origin; 2) research in
      structural anthropology indicates that the tables are a formalization of arrays
      of "symbolic classification" which express a pre-scientific world view with
      social and ethical implications, according to which the presence of a principle
      on one column of the table will carry with it another principle within the same
      column; 3) a close analysis of Aristotle's arguments shows that he thought that
      the table expresses real causal relationships; and 4) Aristotle faults the table
      of opposites with positing its principles as having universal application and
      with not distinguishing between those principles that are causally prior and
      those that are posterior. Aristotle's account of scientific explanation and his
      own explanations that he developed in accordance with this account are in part
      the result of his critical encounter with this prescientific Pythagorean table.

PMID- 25996850
TI  - Chloro-benzoquinones cause oxidative DNA damage through iron-mediated ROS
      production in Escherichia coli.
AB  - Chloro-benzoquinones (CBQs) are a group of disinfection byproducts that are
      suspected to be potentially carcinogenic. Here, the mechanism of DNA damage
      caused by CBQs in the presence of ferrous ions was investigated in an Escherichia
      coli wild type M5 strain and a mutant L5 (ahpCF katEG mutant) strain that carried
      an enhanced green fluorescent protein reporter under the control of a SOS
      response gene (recA) promoter. All tested CBQs (including para-benzoquinone, 2
      chloro-para-benzoquinone, and dichloro-para-benzoquinones with different
      substitutes) caused substantial oxidative DNA damage with EC50 values in the
      micromolar range. Moreover, 2,5-dichloro-para-benzoquinone (2,5-DCBQ), a typical
      CBQ, caused substantial ROS production in E. coli mutant cells. And ROS
      scavengers provided partial protective effects on genotoxicity of 2,5-DCBQ to E.
      coli mutant cells. The addition of Fe(2+) to the 2,5-DCBQ exposure system caused
      an increase in DNA oxidative damage; iron-chelating agents could partially
      prevent these cells from DNA damage. Finally, intracellular AhpCF, catalase E,
      and catalase G were all found to play an important role in the survival of E.
      coli cells exposed to CBQs, as indicated by an increased sensitivity of the ahpCF
      katEG mutant L5 strain to treatment compared with wild type M5 cells. Taken
      together, these results suggest that CBQs cause oxidative DNA damage in E. coli
      cells through the participation of iron-mediated ROS production. 

PMID- 25996853
TI  - Disciplined by the discipline: a social-epistemic fingerprint of the history of
      science.
AB  - ARGUMENT: The scientific system is primarily differentiated into disciplines.
      While disciplines may be wide in scope and diverse in their research practices,
      they serve scientific communities that evaluate research and also grant
      recognition to what is published. The analysis of communication and publication
      practices within such a community hence allows us to shed light on the dynamics
      of this discipline. On the basis of an empirical analysis of Isis, we show how
      the process of discipline-building in history of science has led its
      practitioners to be socialized and sensitized in relatively strong intra
      disciplinary terms--with minimal interdisciplinary openness.

PMID- 25996854
TI  - Modernizing science: between a liberal, social, and socialistic university--the
      case of Poland and the University of Lodz (1945-1953).
AB  - ARGUMENT: This paper examines the postwar reconstruction of the Polish academic
      system. It analyzes a debate that took place in the newly established university
      in the proletarian city of Lodz. The vision of the shape of the university was a
      bone of contention between the professors. This resulted in two contentious
      models of a university: "liberal" and "socialized." Soon, universities were
      transformed into crucial institutions of the emerging communist state, where
      national history, ideology, and the future elite were produced and shaped. The
      social university was transformed into a socialistic university. Analysis of this
      process of transformation enables me to scrutinize the difficult clashes between
      the leftist intellectuals and the rising system of power that was not entirely
      hostile to them. The case of Poland also shows that sovietization did not mean
      solely a ruthless convergence of Central and Eastern Europe with a universal
      model most completely implemented in the USSR. Power hitting the ground was
      redeployed along various local interests, institutional conjunctures, and
      personal intransigencies. On a more universal level, I present this case in the
      context of the challenge of modernization and its many respective accommodations.

PMID- 25996855
TI  - The right time for the job? Insights into practices of time in contemporary field
      sciences.
AB  - ARGUMENT: Temporal issues appear to be crucial to the relationship between life
      scientists and their field sites and to the making of science in the field. We
      elaborate on the notion of practices of time to describe the ways life scientists
      cope with multiple and potentially conflicting temporal aspects that influence
      how they become engaged and remain engaged in a field-site, such as pleasure,
      long-term security, scientific productivity, and timeliness. With this notion, we
      seek to bring enhanced visibility and coherence to the extensive but rather
      scattered and limited treatments of temporal practices in field sciences that
      already exist.

PMID- 25996856
TI  - Strange Birds: Ornithology and the Advent of the Collared Dove in Post-World War
      II Germany.
AB  - ARGUMENT: In this paper I study the engagement of German ornithologists with the
      Collared Dove, a bird species of Asian origin that spread massively throughout
      Central Europe in the 1940s and 1950s. Never before had the spread of a single
      species attracted so much attention from European ornithologists. Ornithologists
      were not only fascinated by the exotic origin of the bird, but even more so by
      the unprecedented rapidity of its expansion. As it is argued in the paper, the
      advent of the bird created an outstanding opportunity for ornithologists to study
      the process of biogeographic range expansion. The paper traces how knowledge on
      the dove's expansion took shape in the social, discursive, and material practices
      of a large-scale observation campaign of German ornithologists (both amateurs and
      academics). The paper also argues that ornithologists' observation practices have
      contributed to the construction of a benevolent cultural image of the Collared
      Dove. This sets the case of the Collared Dove apart from many recent debates in
      which newly arriving species have been framed as a threat to biodiversity. The
      paper contributes both to a historical understanding of scientific fieldwork as
      well as of the role of scientific knowledge in the shaping of cultural meanings
      of animals.

PMID- 25996857
TI  - An integrative framework for the appraisal of coloration in nature.
AB  - The world in color presents a dazzling dimension of phenotypic variation.
      Biological interest in this variation has burgeoned, due to both increased means
      for quantifying spectral information and heightened appreciation for how animals
      view the world differently than humans. Effective study of color traits is
      challenged by how to best quantify visual perception in nonhuman species. This
      requires consideration of at least visual physiology but ultimately also the
      neural processes underlying perception. Our knowledge of color perception is
      founded largely on the principles gained from human psychophysics that have
      proven generalizable based on comparative studies in select animal models.
      Appreciation of these principles, their empirical foundation, and the reasonable
      limits to their applicability is crucial to reaching informed conclusions in
      color research. In this article, we seek a common intellectual basis for the
      study of color in nature. We first discuss the key perceptual principles, namely,
      retinal photoreception, sensory channels, opponent processing, color constancy,
      and receptor noise. We then draw on this basis to inform an analytical framework
      driven by the research question in relation to identifiable viewers and visual
      tasks of interest. Consideration of the limits to perceptual inference guides two
      primary decisions: first, whether a sensory-based approach is necessary and
      justified and, second, whether the visual task refers to perceptual distance or
      discriminability. We outline informed approaches in each situation and discuss
      key challenges for future progress, focusing particularly on how animals perceive
      color. Given that animal behavior serves as both the basic unit of psychophysics
      and the ultimate driver of color ecology/evolution, behavioral data are critical
      to reconciling knowledge across the schools of color research. 

PMID- 25996858
TI  - Origin matters: diversity affects the performance of alien invasive species but
      not of native species.
AB  - At local scales, it has often been found that invasibility decreases with
      increasing resident plant diversity. However, whether resident community
      diversity similarly resists invasion by alien versus native species is seldom
      studied. We examined this issue by invading constructed native plant assemblages
      that varied in species and functional richness with invasive alien or native
      Asteraceae species. Assemblages were also invaded with spotted knapweed,
      Centaurea stoebe, a native European aster that has been previously used in
      diversity-invasibility experiments in North America. We also conducted a field
      survey to explore the generality of the patterns generated from our experimental
      study. Both experimental and observational work revealed that increasing
      diversity reduced the performance of alien but not native invaders. Centaurea
      stoebe invading its native community performed poorly regardless of resident
      diversity, whereas in a parallel, previously published study conducted in North
      America, C. stoebe easily invaded low-diversity but not high-diversity
      assemblages. Our results suggest that diversity is an attribute of resident
      communities that makes them more or less susceptible to invasion by novel
      invasive alien but not native plant species. 

PMID- 25996859
TI  - Intraspecific trait variation is correlated with establishment success of alien
      mammals.
AB  - Many studies have aimed to identify common predictors of successful introductions
      of alien species, but the search has had limited success, particularly for
      animals. Past research focused primarily on mean trait values, even though
      genetic and phenotypic variation has been shown to play a role in establishment
      success in plants and some animals (mostly invertebrates). Using a global
      database describing 511 introduction events representing 97 mammalian species, we
      show that intraspecific variation in morphological traits is associated with
      establishment success, even when controlling for the positive effect of propagule
      pressure. In particular, greater establishment success is associated with more
      variation in adult body size but, surprisingly, less variation in neonate body
      size, potentially reflecting distinct trade-offs and constraints that influence
      population dynamics differently. We find no mean trait descriptors associated
      with establishment success, although species occupying wider native distribution
      ranges (which likely have larger niches) are more successful. Our results
      emphasize the importance of explicitly considering intraspecific variation to
      predict establishment success in animal species and generally to understand
      population dynamics. This understanding might improve management of alien species
      and increase the success of intentional releases, for example, for biocontrol or
      reintroductions. 

PMID- 25996860
TI  - Testing the Shifting Persistence Niche Concept: Plant Resprouting along Gradients
      of Disturbance.
AB  - Plant resprouting after disturbance confers community resilience because
      individuals persist through trade-offs in resources for buds versus those
      required to produce seeds. However, repeated disturbance may deplete bud banks,
      and population persistence may become increasingly reliant on regeneration from
      seed. Theory predicts a shift in community assemblage from species with a
      strategy of persistence by resprouting (persistence niche) to one of regeneration
      from seed (regeneration niche) as the disturbance frequency increases. We tested,
      for the first time, the shifting persistence niche concept in a model system at
      local and regional community scales using a phylogenetically diverse floristic
      assemblage. Persistence traits of vascular plants were modeled as a function of
      dry-down frequency in wetlands. Resprouting species occupying the persistence
      niche were more common in stable wetlands than in those more frequently disturbed
      by dry downs. The patterns of resprouting species in standing vegetation and in
      seed banks provide strong support for the shifting persistence niche model
      involving trade-offs between resprouting (clonality) and sexual reproduction. 

PMID- 25996861
TI  - Environment-Dependent Sexual Selection: Bateman's Parameters under Varying Levels
      of Food Availability.
AB  - Sexual selection is a potent evolutionary force that has been shown to vary in
      strength and direction depending on demographic factors such as density and sex
      ratio. However, the effect of other environmental factors on the mode of sexual
      selection remains largely unexplored. Here, we tested experimentally how food
      restriction affects the potential for sexual selection in the male and the female
      sex function of the simultaneously hermaphroditic freshwater snail Physa acuta.
      We manipulated food availability and compared Bateman's metrics of sexual
      selection between groups of five well-fed and five food-restricted snails. Food
      restricted individuals had a reduced female reproductive output, suggesting that
      we successfully manipulated the reproductive resources. Importantly, food
      restriction reduced the male opportunity for sexual selection (in terms of a
      lowered variance in male mating success) and led to diminishing returns of mating
      in both sexes (in terms of nonsignificant Bateman gradients). Furthermore, we
      observed significant changes in the relative contribution of different fitness
      components, suggesting stronger postcopulatory selection in the male sex role and
      stronger fecundity selection in the female sex role under restricted food
      conditions. This study highlights the need to incorporate ecological factors to
      better understand how sexual selection operates in the wild. 

PMID- 25996863
TI  - The Roles of Ecological and Evolutionary Processes in Plant Community Assembly:
      The Environment, Hybridization, and Introgression Influence Co-occurrence of
      Eucalyptus.
AB  - Introgressive hybridization is increasingly recognized as having influenced the
      gene pools of large genera of plants, yet it is rarely invoked as an explanation
      for why closely related plant species do not co-occur. Here, we asked how the
      environment and tendency to interbreed relate to neighborhood co-occurrence
      patterns for Eucalyptus species in the Grampians National Park, Victoria,
      Australia. We identified species pairs that have experienced ongoing
      hybridization and introgression on the basis of the extent of incongruence
      between chloroplast DNA (JLA+ region) and nuclear ribosomal DNA (internal
      transcribed spacer region) phylogenies, geographic patterns of gene sharing, and
      field observation of intermediate morphologies. Co-occurrence, trait data
      (specific leaf area [SLA], maximum height, and seed mass), and environmental data
      were measured in plots distributed along environmental gradients. Trait and
      habitat similarity influenced species co-occurrence the most overall (e.g., co
      occurring species had similar SLA). Reproductively compatible species were an
      exception; they rarely co-occurred despite being functionally similar. The
      negative effect of reproductive compatibility was stronger than the positive
      effect of SLA on co-occurrence. Our results emphasize the dominant roles of the
      environment and the importance of evolution in structuring local assemblages. We
      argue that the mechanism responsible for preventing closely related species from
      co-occurring in this system is reproductive interference rather than competitive
      exclusion. Reproductive interference should be considered more generally as a
      potential cause of phylogenetic overdispersion. 

PMID- 25996862
TI  - Immune activation generates corticosterone-mediated terminal reproductive
      investment in a wild bird.
AB  - Despite classical expectations of a trade-off between immune activity and
      reproduction, an emergent view suggests that individuals experiencing activation
      of their immune system actually increase reproductive effort and allocation to
      offspring as a form of terminal investment in response to reduced survival
      probability. However, the components and mechanisms of increased parental
      investment following immunostimulation are currently unknown. We hypothesize that
      increased glucocorticoid production following immunostimulation modulates the
      increase in reproductive effort that constitutes terminal investment. We
      activated the immune system of breeding female house wrens (Troglodytes aedon)
      with an immunogen and cross-fostered the eggs that they subsequently produced to
      separate prenatal and postnatal components of maternal investment. Cross
      fostering revealed an increase in both pre- and postnatal allocation from
      immunostimulated females, which was confirmed by quantification of egg
      constituents and maternal provisioning behavior. The increase in maternal
      provisioning was mediated, at least in part, by increased corticosterone in these
      females. Offspring immune responsiveness was also enhanced through
      transgenerational immune priming via the egg. Thus, our results indicate that
      maternal immunostimulation induces transgenerational effects on offspring through
      both pre- and postnatal parental effects and support an important role for
      corticosterone in mediating parental investment. 

PMID- 25996864
TI  - A Bayesian Approach to Social Structure Uncovers Cryptic Regulation of Group
      Dynamics in Drosophila melanogaster.
AB  - Understanding the mechanisms that give rise to social structure is central to
      predicting the evolutionary and ecological outcomes of social interactions.
      Modeling this process is challenging, because all individuals simultaneously
      behave in ways that shape their social environments--a process called social
      niche construction (SNC). In earlier work, we demonstrated that aggression acts
      as an SNC trait in fruit flies (Drosophila melanogaster), but the mechanisms of
      that process remained cryptic. Here, we analyze how individual social group
      preferences generate overall social structure. We use a combination of agent
      based simulation and approximate Bayesian computation to fit models to empirical
      data. We confirm that genetic variation in aggressive behavior influences social
      group structure. Furthermore, we find that female decamping due to male behavior
      may play an underappreciated role in structuring social groups. Male-male
      aggression may sometimes destabilize groups, but it may also be an SNC behavior
      for shaping desirable groups for females. Density intensifies female social
      preferences; thus, the role of female behavior in shaping group structure may
      become more important at high densities. Our ability to model the ontogeny of
      group structure demonstrates the utility of the Bayesian model-based approach in
      social behavioral studies.

PMID- 25996865
TI  - Developmental constraints in a wild primate.
AB  - Early-life experiences can dramatically affect adult traits. However, the
      evolutionary origins of such early-life effects are debated. The predictive
      adaptive response hypothesis argues that adverse early environments prompt
      adaptive phenotypic adjustments that prepare animals for similar challenges in
      adulthood. In contrast, the developmental constraints hypothesis argues that
      early adversity is generally costly. To differentiate between these hypotheses,
      we studied two sets of wild female baboons: those born during low-rainfall, low
      quality years and those born during normal-rainfall, high-quality years. For each
      female, we measured fertility-related fitness components during years in
      adulthood that matched and mismatched her early conditions. We found support for
      the developmental constraints hypothesis: females born in low-quality
      environments showed greater decreases in fertility during drought years than
      females born in high-quality environments, even though drought years matched the
      early conditions of females born in low-quality environments. Additionally, we
      found that females born in low-quality years to high-status mothers did not
      experience reduced fertility during drought years. These results indicate that
      early ecological adversity did not prepare individuals to cope with ecological
      challenges in later life. Instead, individuals that experienced at least one high
      quality early environment--either ecological or social--were more resilient to
      ecological stress in later life. Together, these data suggest that early
      adversity carries lifelong costs, which is consistent with the developmental
      constraints hypothesis.

PMID- 25996866
TI  - The comparative effects of large carnivores on the acquisition of carrion by
      scavengers.
AB  - Pumas (Puma concolor) and black bears (Ursus americanus) are large carnivores
      that may influence scavenger population dynamics. We used motion-triggered video
      cameras deployed at deer carcasses to determine how pumas and black bears
      affected three aspects of carrion acquisition by scavengers: presence, total
      feeding time, and mean feeding-bout duration. We found that pumas were unable to
      limit acquisition of carrion by large carnivores but did limit aspects of carrion
      acquisition by both birds and mesocarnivores. Through their suppression of
      mesocarnivores and birds, pumas apparently initiated a cascading pattern and
      increased carrion acquisition by small carnivores. In contrast, black bears
      monopolized carrion resources and generally had larger limiting effects on
      carrion acquisition by all scavengers. Black bears also limited puma feeding
      behaviors at puma kills, which may require pumas to compensate for energetic
      losses through increasing their kill rates of ungulates. Our results suggest that
      pumas provide carrion and selectively influence species acquiring carrion, while
      black bears limit carrion availability to all other scavengers. These results
      suggest that the effects of large carnivores on scavengers depend on attributes
      of both carnivores and scavengers (including size) and that competition for
      carcasses may result in intraguild predation as well as mesocarnivore release. 

PMID- 25996867
TI  - A new approach to the generation time in matrix population models.
AB  - The generation time is commonly defined as the mean age of mothers at birth. In
      matrix population models, a general formula is available to compute this
      quantity. However, it is complex and hard to interpret. Here, we present a new
      approach where the generation time is envisioned as a return time in an
      appropriate Markov chain. This yields surprisingly simple results, such as the
      fact that the generation time is the inverse of the sum of the elasticities of
      the growth rate to changes in the fertilities. This result sheds new light on the
      interpretation of elasticities (which as we show correspond to the frequency of
      events in the ancestral lineage of the population), and we use it to generalize a
      result known as Lebreton's formula. Finally, we also show that the generation
      time can be seen as a random variable, and we give a general expression for its
      distribution. 

PMID- 25996868
TI  - Genetic variation, simplicity, and evolutionary constraints for function-valued
      traits.
AB  - Understanding the patterns of genetic variation and constraint for continuous
      reaction norms, growth trajectories, and other function-valued traits is
      challenging. We describe and illustrate a recent analytical method, simple basis
      analysis (SBA), that uses the genetic variance-covariance (G) matrix to identify
      "simple" directions of genetic variation and genetic constraints that have
      straightforward biological interpretations. We discuss the parallels between the
      eigenvectors (principal components) identified by principal components analysis
      (PCA) and the simple basis (SB) vectors identified by SBA. We apply these methods
      to estimated G matrices obtained from 10 studies of thermal performance curves
      and growth curves. Our results suggest that variation in overall size across all
      ages represented most of the genetic variance in growth curves. In contrast,
      variation in overall performance across all temperatures represented less than
      one-third of the genetic variance in thermal performance curves in all cases, and
      genetic trade-offs between performance at higher versus lower temperatures were
      often important. The analyses also identify potential genetic constraints on
      patterns of early and later growth in growth curves. We suggest that SBA can be a
      useful complement or alternative to PCA for identifying biologically
      interpretable directions of genetic variation and constraint in function-valued
      traits. 

PMID- 25996869
TI  - Evolutionary time-series analysis reveals the signature of frequency-dependent
      selection on a female mating polymorphism.
AB  - A major challenge in evolutionary biology is understanding how stochastic and
      deterministic factors interact and influence macroevolutionary dynamics in
      natural populations. One classical approach is to record frequency changes of
      heritable and visible genetic polymorphisms over multiple generations. Here, we
      combined this approach with a maximum likelihood-based population-genetic model
      with the aim of understanding and quantifying the evolutionary processes
      operating on a female mating polymorphism in the blue-tailed damselfly Ischnura
      elegans. Previous studies on this color-polymorphic species have suggested that
      males form a search image for females, which leads to excessive mating harassment
      of common female morphs. We analyzed a large temporally and spatially replicated
      data set of between-generation morph frequency changes in I. elegans. Morph
      frequencies were more stable than expected from genetic drift alone, suggesting
      the presence of selection toward a stable equilibrium that prevents local loss or
      fixation of morphs. This can be interpreted as the signature of negative
      frequency-dependent selection maintaining the phenotypic stasis and genetic
      diversity in these populations. Our novel analytical approach allows the
      estimation of the strength of frequency-dependent selection from the morph
      frequency fluctuations around their inferred long-term equilibria. This approach
      can be extended and applied to other polymorphic organisms for which time-series
      data across multiple generations are available. 

PMID- 25996870
TI  - Hybrid breakdown in cichlid fish.
AB  - Studies from a wide diversity of taxa have shown a negative relationship between
      genetic compatibility and the divergence time of hybridizing genomes. Theory
      predicts the main breakdown of fitness to happen after the F1 hybrid generation,
      when heterosis subsides and recessive allelic (Dobzhansky-Muller)
      incompatibilities are increasingly unmasked. We measured the fitness of F2
      hybrids of African haplochromine cichlid fish bred from species pairs spanning
      several thousand to several million years divergence time. F2 hybrids
      consistently showed the lowest viability compared to F1 hybrids and non-hybrid
      crosses (crosses within the grandparental species), in agreement with hybrid
      breakdown. Especially the short- and long-term survival (2 weeks to 6 months) of
      F2 hybrids was significantly reduced. Overall, F2 hybrids showed a fitness
      reduction of 21% compared to F1 hybrids, and a reduction of 43% compared to the
      grandparental, non-hybrid crosses. We further observed a decrease of F2 hybrid
      viability with the genetic distance between grandparental lineages, suggesting an
      important role for negative epistatic interactions in cichlid fish postzygotic
      isolation. The estimated time window for successful production of F2 hybrids
      resulting from our data is consistent with the estimated divergence time between
      the multiple ancestral lineages that presumably hybridized in three major
      adaptive radiations of African cichlids. 

PMID- 25996871
TI  - [Bilateral Instability of the Interphalangeal Articulation of the Thumb in Hajdu
      Cheney Syndrome].
AB  - We present the case of a 52-year-old lady suffering from Hajdu-Cheney syndrome, a
      rare hereditary disease, which was referred to our clinic on the basis of
      progressive instability of the interpalangeal articulations of both thumbs. Even
      if acroosteolysis of the distal phalangeal bones is typical for this disease, to
      the best of our knowledge the interphalangeal instability has not been described
      before. 

PMID- 25996872
TI  - [Massive Destruction of the Carpus after Partial Arthrodesis Caused by
      Tuberculosis].
AB  - We present the case of a 75-year-old woman who suffered from a severe carpal
      collapse caused by tuberculosis after partial wrist arthrodesis. 

PMID- 25996874
TI  - Self-Assembled Nanoparticles of Amphiphilic Twin Drug from Floxuridine and
      Bendamustine for Cancer Therapy.
AB  - We report here an amphiphilic twin drug strategy directly using small molecular
      hydrophilic and hydrophobic anticancer drugs to self-assemble into nanoparticles
      with a high and fixed drug content, which can solve problems of anticancer drug
      delivery including poor water solubility, low therapeutic indices, and severe
      side effects. The twin drug has been prepared by the esterification of the
      hydrophilic anticancer drug floxuridine (FdU) with the hydrophobic anticancer
      drug bendamustine (BdM). Due to its inherent amphiphilicity, the FdU-BdM twin
      drug can self-assemble into stable and well-defined nanoparticles. After FdU-BdM
      twin drug enters into cells, the ester linkage between hydrophilic and
      hydrophobic drugs is readily cleaved by hydrolysis to release free FdU and BdM.
      Since both FdU and BdM can kill cancer cells, the FdU-BdM twin drug nanoparticles
      can overcome the multidrug resistance (MDR) of tumor cells and present an
      excellent anticancer activity. This strategy can be extended to other hydrophilic
      and hydrophobic anticancer drugs to synthesize amphiphilic twin drugs which can
      form nanoparticles to self-deliver drugs for cancer therapy. 

PMID- 25996873
TI  - TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required
      for Spermatogenesis.
AB  - Intracellular calcium signaling is critical for initiating and sustaining diverse
      cellular functions including transcription, synaptic signaling, muscle
      contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was
      identified here in cDNA overexpression screens for proteins capable of modulating
      intracellular calcium levels using activation of a calcium/calcineurin regulated
      transcription factor as an indicator. Overexpression of TMEM203 resulted in a
      reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal
      cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found
      associated with a number of ER proteins which regulate ER calcium entry and
      efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice
      had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient
      mice were viable though male knockout mice were infertile and exhibited a severe
      block in spermiogenesis and spermiation. Expression profiling studies showed
      significant alternations in expression of calcium channels and pumps in testes
      and concurrently Tmem203 deficient spermatocytes demonstrated significantly
      altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator
      of cellular calcium homeostasis, is required for spermatogenesis and provides a
      causal link between intracellular calcium regulation and spermiogenesis. 

PMID- 25996875
TI  - Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and
      pharmacokinetics.
AB  - In neurological malignancies, antiepileptic drugs (AEDs) are frequently used to
      control the seizure activity that accompanies the disorder. There is a growing
      body of evidence on the importance of AED selection for reasons other than
      pharmacokinetics (PK) properties. Epigenetic modifications may occur in
      glioblastomas, such as changes in gene methylation and histone acetylation
      states. Secondary mechanisms of AED drug action which impact these epigenetic
      modifications could play a significant role in patient survival outcomes. Both
      valproic acid (VPA) and carbamazepine have histone deacetylase (HDAC) inhibitory
      activities, and levetiracetam and VPA reduce the activity of O6-methylguanine-DNA
      methyltransferase (MGMT), a DNA-repair molecule implicated in resistance to
      alkylating agents used for chemotherapy. The use of AEDs for purposes other than
      seizure prophylaxis and their selection based on non-PK properties present a
      potential paradigm shift in the field of neuro-oncology. 

PMID- 25996876
TI  - Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles
      Tendinopathy.
AB  - BACKGROUND: Achilles tendinopathy is a painful inflammatory condition
      characterized by swelling, stiffness and reduced function of the Achilles tendon.
      Kager's fat pad is an adipose tissue located in the area anterior to the Achilles
      tendon. Observations reveal a close physical interplay between Kager's fat pad
      and its surrounding structures during movement of the ankle, suggesting that
      Kager's fat pad may stabilize and protect the mechanical function of the ankle
      joint. AIM: The aim of this study was to characterize whether Achilles
      tendinopathy was accompanied by changes in expression of inflammatory markers and
      metabolic enzymes in Kager's fat pad. METHODS: A biopsy was taken from Kager's
      fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy
      individuals. Gene expression was measured by reverse transcription-quantitative
      PCR. Focus was on genes related to inflammation and lipid metabolism. RESULTS:
      Expression of the majority of analyzed inflammatory marker genes was increased in
      patients with Achilles tendinopathy compared to that in healthy controls.
      Expression patterns of the patient group were consistent with reduced lipolysis
      and increased fatty acid beta-oxidation. In the fat pad, the pain-signaling
      neuropeptide substance P was found to be present in one third of the subjects in
      the Achilles tendinopathy group but in none of the healthy controls. CONCLUSION:
      Gene expression changes in Achilles tendinopathy patient samples were consistent
      with Kager's fat pad being more inflamed than in the healthy control group.
      Additionally, the results indicate an altered lipid metabolism in Kager's fat pad
      of Achilles tendinopathy patients.

PMID- 25996877
TI  - Evaluation of Brachypodium distachyon L-Tyrosine Decarboxylase Using L-Tyrosine
      Over-Producing Saccharomyces cerevisiae.
AB  - To demonstrate that herbaceous biomass is a versatile gene resource, we focused
      on the model plant Brachypodium distachyon, and screened the B. distachyon for
      homologs of tyrosine decarboxylase (TDC), which is involved in the modification
      of aromatic compounds. A total of 5 candidate genes were identified in cDNA
      libraries of B. distachyon and were introduced into Saccharomyces cerevisiae to
      evaluate TDC expression and tyramine production. It is suggested that two TDCs
      encoded in the transcripts Bradi2g51120.1 and Bradi2g51170.1 have L-tyrosine
      decarboxylation activity. Bradi2g51170.1 was introduced into the L-tyrosine over
      producing strain of S. cerevisiae that was constructed by the introduction of
      mutant genes that promote deregulated feedback inhibition. The amount of tyramine
      produced by the resulting transformant was 6.6-fold higher (approximately 200
      mg/L) than the control strain, indicating that B. distachyon TDC effectively
      converts L-tyrosine to tyramine. Our results suggest that B. distachyon possesses
      enzymes that are capable of modifying aromatic residues, and that S. cerevisiae
      is a suitable host for the production of L-tyrosine derivatives. 

PMID- 25996878
TI  - Combination of circulating tumor cells with serum carcinoembryonic antigen
      enhances clinical prediction of non-small cell lung cancer.
AB  - Circulating tumor cells (CTCs) have emerged as a potential biomarker in the
      diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC
      detection is not only costly, but its sensitivity is also low, thus limiting its
      usage and the collection of robust data regarding the significance of CTCs in
      lung cancer. We aimed to seek clinical variables that enhance the prediction of
      CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and
      pathological data were collected from 169 NSCLC patients. CTCs were detected by
      CellSearch and tumor markers were detected using the Luminex xMAP assay.
      Univariate analyses revealed that histology, tumor stage, tumor size,
      invasiveness, tumor grade and carcinoembryonic antigen (CEA) were associated with
      the presence of CTCs. However, the level of CTCs was not associated with the
      degree of nodal involvement (N) or tumor prognostic markers Ki-67, CA125, CA199,
      Cyfra21-1, and SCCA. Using logistic regression analysis, we found that the
      combination of CTCs with tumor marker CEA has a better disease prediction.
      Advanced stage NSCLC patients with elevated CEA had higher numbers of CTCs. These
      data suggest a useful prediction model by combining CTCs with serum CEA in NSCLC
      patients. 

PMID- 25996879
TI  - Effect of Rhizobium sp. BARIRGm901 inoculation on nodulation, nitrogen fixation
      and yield of soybean (Glycine max) genotypes in gray terrace soil.
AB  - Soybean plants require high amounts of nitrogen, which are mainly obtained from
      biological nitrogen fixation. A field experiment was conducted by soybean
      (Glycine max) genotypes, growing two varieties (Shohag and BARI Soybean6) and two
      advanced lines (MTD10 and BGM02026) of soybean with or without Rhizobium sp.
      BARIRGm901 inoculation. Soybean plants of all genotypes inoculated with Rhizobium
      sp. BARIRGm901 produced greater nodule numbers, nodule weight, shoot and root
      biomass, and plant height than non-inoculated plants. Similarly, inoculated
      plants showed enhanced activity of nitrogenase (NA) enzyme, contributing to
      higher nitrogen fixation and assimilation, compared to non-inoculated soybean
      plants in both years. Plants inoculated with Rhizobium sp. BARIRGm901 also showed
      higher pod, stover, and seed yield than non-inoculated plants. Therefore,
      Rhizobium sp. BARIRGm901 established an effective symbiotic relationship with a
      range of soybean genotypes and thus increased the nodulation, growth, and yield
      of soybean grown in gray terrace soils in Bangladesh. 

PMID- 25996880
TI  - Association between male sex and increased mortality after falls.
AB  - OBJECTIVES: Whether sex affects the mortality of trauma patients remains unknown.
      The hypothesis of this study was that sex was associated with altered mortality
      rates in trauma. METHODS: A retrospective review of trauma patients' records in
      the Japan Trauma Data Bank was conducted (n = 80,813) from 185 major emergency
      hospitals across Japan. The primary outcome variable was in-hospital mortality
      within 28 days. Secondary outcome variables included serious injuries to
      different body regions with an Abbreviated Injury Scale of >=3. RESULTS: In the
      analysis of 80,813 trauma patients, males had significantly greater 28-day
      mortality compared to females (adjusted p = 0.0072, odds ratio [OR] = 1.14, 95%
      confidence interval [CI] = 1.06 to 1.23) via logistic regression analysis
      adjusted for age, mechanism, Injury Severity Score, Revised Trauma Score, and
      potential preexisting risk factors. Of 10 injury categories examined, sex
      significantly affected in-hospital 28-day mortality rate in falls (adjusted p <
      0.0001, OR = 1.34, 95% CI = 1.19 to 1.52). Further analysis of three fall
      subcategories by falling distance revealed that male patients who fell from
      ground level had significantly higher 28-day mortality (adjusted p < 0.0001, OR =
      1.75, 95% CI = 1.43 to 2.14) and a significantly greater frequency of serious
      injury to the head, thorax, abdomen, and spine, but a lower frequency of serious
      injury to the extremities, compared to female patients. CONCLUSIONS: Compared to
      female trauma patients, male trauma patients had greater 28-day mortality. In
      particular, ground-level falls had a significant sex difference in mortality,
      with serious injury to different body regions. Sex differences appeared to be
      important for fatalities from ground-level falls.

PMID- 25996881
TI  - Renal transplantation experience in a patient with factor V Leiden homozygous,
      MTHFR C677T heterozygous, and PAI heterozygous mutation.
AB  - Vascular complications are important causes of allograft loss in renal
      transplantation. A two and a half-month-old boy was diagnosed with posterior
      urethral valve and progressed to end-stage renal disease at eight yr of age.
      During the HD period, a central venous catheter was replaced three times for
      repeated thrombosis. The boy was found to be homozygous for FVL and heterozygous
      for both MTHFR (C677T) and PAI. At the age of 12, renal transplantation was
      performed from a deceased donor. Postoperative anticoagulation therapy was
      initiated with continuous intravenous administration of heparin at the dose of 10
      IU/kg/h. HD was performed for the first three days. By the fourth day of
      transplantation, his urine output had increased gradually. Heparin infusion was
      continued for 18 days during hospitalization at the same dosage. Thereafter, he
      was discharged with LMWH. On the third month after transplantation, his serum
      creatinine level was 1.1 mg/dL and eGFR was 75.7 mL/min/1.73 m(2). He has still
      been using LMWH, and his eGFR was 78.7 mL/min/1.73 m(2) eight months after
      transplantation. Postoperative low-dose heparin treatment is a safe strategy for
      managing a patient with multiple thrombotic risk factors.

PMID- 25996883
TI  - In the letter to the editor from Fudge and Helmreich, the authors related to our
      recent publication (Cymerblit-Sabbaet al., 2015).

PMID- 25996882
TI  - Arterial hypertension and skin allergy are risk factors for progression from
      dengue to dengue hemorrhagic fever: a case control study.
AB  - BACKGROUND: Currently, knowledge does not allow early prediction of which cases
      of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow
      early intervention to prevent progression or to limit severity. The objective of
      this study is to investigate the hypothesis that some specific comorbidities
      increase the likelihood of a DF case progressing to DHF. METHODS: A concurrent
      case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases
      were patients with dengue fever that progressed to DHF, and controls were
      patients of dengue fever who did not progress to DHF. Logistic regression was
      used to estimate the association between DHF and comorbidities. RESULTS: There
      were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was
      associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin
      allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and
      socio-economic variables. There was no statistically significant association
      between any chronic disease and progression to DHF in those younger than 15
      years. CONCLUSIONS: Physicians attending patients with dengue fever should keep
      those with hypertension or skin allergies in health units to monitor progression
      for early intervention. This would reduce mortality by dengue.

PMID- 25996884
TI  - Principles Relevant to Health Research among Indigenous Communities.
AB  - Research within Indigenous communities has been criticised for lacking community
      engagement, for being exploitative, and for poorly explaining the processes of
      research. To address these concerns, and to ensure 'best practice', Jamieson, et
      al. (2012) recently published a summary of principles outlined by the NHMRC
      (2003) in "one short, accessible document". Here we expand on Jamieson et al.'s
      paper, which while commendable, lacks emphasis on the contribution that
      communities themselves can make to the research process and how culturally
      appropriate engagement, can allow this contribution to be assured, specifically
      with respect to engagement with remote communities. Engagement started before the
      research proposal is put forward, and continued after the research is completed,
      has integrity. We emphasise the value of narratives, of understanding cultural
      and customary behaviours and leadership, the importance of cultural legitimacy,
      and of the need for time, not just to allow for delays, but to ensure genuine
      participatory engagement from all members of the community. We also challenge
      researchers to consider the outcomes of their research, on the basis that
      increasing clinical evidence does not always result in better outcomes for the
      community involved. 

PMID- 25996885
TI  - Adult psychotic symptoms, their associated risk factors and changes in prevalence
      in men and women over a decade in a poor rural district of Kenya.
AB  - There have been no repeat surveys of psychotic symptoms in Kenya or indeed
      subSaharan Africa. A mental health epidemiological survey was therefore conducted
      in a demographic surveillance site of a Kenyan household population in 2013 to
      test the hypothesis that the prevalence of psychotic symptoms would be similar to
      that found in an earlier sample drawn from the same sample frame in 2004, using
      the same overall methodology and instruments. This 2013 study found that the
      prevalence of one or more psychotic symptoms was 13.9% with one or more symptoms
      and 3.8% with two or more symptoms, while the 2004 study had found that the
      prevalence of single psychotic symptoms in rural Kenya was 8% of the adult
      population, but only 0.6% had two symptoms and none had three or more psychotic
      symptoms. This change was accounted for by a striking increase in psychotic
      symptoms in women (17.8% in 2013 compared with 6.9% in 2004, p < 0.001), whereas
      there was no significant change in men (10.6% in 2013 compared with 9.4% in 2004,
      p = 0.582). Potential reasons for this increase in rate of psychotic symptoms in
      women are explored. 

PMID- 25996886
TI  - Elevated serum Bisphenol A level in patients with dilated cardiomyopathy.
AB  - BACKGROUND: This study aimed to determine serum Bisphenol A (BPA) concentrations
      in patients with dilated cardiomyopathy (DCM) as well as the association between
      serum BPA and several hormonal parameters in DCM patients compared with a healthy
      control group. MATERIALS AND METHODS: Eighty-eight DCM patients and 88 age- and
      gender-matched healthy controls were included. Serum BPA levels and several
      hormonal parameters (including total testosterone (T), sex hormone-binding
      globulin (SHBG) and estradiol (E2) were measured by using corresponding ELISA
      Kits. The free androgen index (FAI) was calculated by the formula: total T in
      nmol/L * 100/SHBG in nmol/L. RESULTS: BPA levels in the total DCM group were
      significantly higher compared with that in the controls (6.9 +/- 2.7 ng/mL vs.
      3.8 +/- 1.9 ng/mL, p < 0.001). Significant difference was also observed in SHBG
      and FAI between DCM patients and controls, (76.9 +/- 30.9 nM/L vs. 41.0 +/- 15.6
      nM/L and 2.9 +/- 3.5 vs.5.3 +/- 2.6, respectively, both of p < 0.001). Similar
      trends were observed in the male and female subgroup. Mean T level was lower in
      DCM group than in control group (540.8 +/- 186.0 pg/mL vs. 656.3 +/- 112.9 pg/mL,
      p < 0.001). Linear regression analysis has shown that increasing serum BPA levels
      were statistically significantly associated with increased SHBG levels. However,
      no statistical difference was noted for E2. CONCLUSION: Our findings firstly
      demonstrated that BPA exposure increased in DCM patients compared with that in
      healthy controls, while FAI and T levels decreased. SHBG presented a positive
      association with BPA. It is concluded that hormone disorder induced by BPA
      exposure might be an environmental factor in the pathology of DCM.

PMID- 25996887
TI  - Radio Hazard Safety Assessment for Marine Ship Transmitters: Measurements Using a
      New Data Collection Method and Comparison with ICNIRP and ARPANSA Limits.
AB  - We investigated the levels of radio frequency electromagnetic fields (RF EMFs)
      emitted from marine ship transmitters. In this study, we recorded the radio
      frequency (RF) electric field (EF) levels emitted from transmitters from a marine
      vessel focusing on the areas normally occupied by crew members and passengers.
      Previous studies considered radiation hazard safety assessment for marine vessels
      with a limited number of transmitters, such as very high-frequency (VHF)
      transceivers, radar and communication transmitters. In our investigation, EF
      levels from seven radio transmitters were measured, including: VHF, medium
      frequency/high frequency (MF/HF), satellite communication (Sat-Com C),
      AISnavigation, radar X-band and radar S-band. Measurements were carried out in a
      40 m-long, three-level ship (upper deck, bridge deck and bridge roof) at 12
      different locations. We developed a new data-collection protocol and performed it
      under 11 different scenarios to observe and measure the radiation emissions from
      all of the transmitters. In total, 528 EF field measurements were collected and
      averaged over all three levels of the marine ship with RF transmitters: the
      measured electric fields were the lowest on the upper deck (0.82-0.86 V/m), the
      highest on the bridge roof (2.15-3.70 V/m) and in between on the bridge deck
      (0.47-1.15 V/m). The measured EF levels were then assessed for compliance with
      the occupational and general public reference levels of the International
      Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines and the
      Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) standards.
      The ICNIRP and the ARPANSA limits for the general public were exceeded on the
      bridge roof; nevertheless, the occupational limits were respected everywhere. The
      measured EF levels, hence, complied with the ICNIRP guidelines and the ARPANSA
      standards. In this paper, we provide a new data collection model for future
      surveys, which could be conducted with larger samples to verify our observations.
      Furthermore, this new method could be useful as a reference for researchers and
      industry professionals without direct access to the necessary equipment. 

PMID- 25996888
TI  - Traffic, air pollution, minority and socio-economic status: addressing inequities
      in exposure and risk.
AB  - Higher levels of nearby traffic increase exposure to air pollution and adversely
      affect health outcomes. Populations with lower socio-economic status (SES) are
      particularly vulnerable to stressors like air pollution. We investigated
      cumulative exposures and risks from traffic and from MNRiskS-modeled air
      pollution in multiple source categories across demographic groups. Exposures and
      risks, especially from on-road sources, were higher than the mean for minorities
      and low SES populations and lower than the mean for white and high SES
      populations. Owning multiple vehicles and driving alone were linked to lower
      household exposures and risks. Those not owning a vehicle and walking or using
      transit had higher household exposures and risks. These results confirm for our
      study location that populations on the lower end of the socio-economic spectrum
      and minorities are disproportionately exposed to traffic and air pollution and at
      higher risk for adverse health outcomes. A major source of disparities appears to
      be the transportation infrastructure. Those outside the urban core had lower
      risks but drove more, while those living nearer the urban core tended to drive
      less but had higher exposures and risks from on-road sources. We suggest policy
      considerations for addressing these inequities. 

PMID- 25996889
TI  - Ethnic differences in the prevalence of high homocysteine levels among low-income
      rural Kazakh and Uyghur adults in far western China and its implications for
      preventive public health.
AB  - OBJECTIVE: Homocysteine (Hcy) is a relevant biomarker of vascular disease: serum
      Hcy concentrations will increase the risk of systolic hypertension, whereas
      hyperhomocysteinemia (HHcy) has a synergistic effect with hypertension and
      increases the risk of cardiovascular disease. However, information has primarily
      been gathered from high-income and urban settings, and little is known regarding
      low-income rural settings. This study focused on a low-income rural and nomadic
      minority residing in far western China. Hcy levels were tested, and the
      prevalences of HHcy and H-type hypertension were investigated in this population.
      METHODS: This study used a stratified cluster random sampling method, selecting
      2,180 individuals as subjects from Kazakh and Uyghur inhabitants (>=25 years old)
      of 18 villages in Xinjiang, China, which is approximately 4407 km from the
      capital, Beijing. Hcy levels were determined using a double reagent enzymatic
      cycling method. HHcy (Hcy > 10 MUmol/L) was defined by the criteria of the
      American Heart Association. RESULTS: The Kazakh geometrical mean of Hcy was 13.34
      MUmol/L, and the Uyghur mean was 13.75 MUmol/L; the mean values were higher in
      males than in females of both ethnicities (15.99 MUmol/L vs. 11.63 MUmol/L; 15.71
      MUmol/L vs. 11.91 MUmol/L, respectively, p < 0.01). The serum levels of Hcy
      increased with increasing age in both ethnicities, and except for Kazakh
      individuals >65 years old, Hcy serum levels were higher in males than in females
      in all age groups of both ethnicities, with a p value less than 0.01. The Kazakh
      prevalence of HHcy was 80.0%, and the Uyghur prevalence was 78.2%; the male
      prevalence was higher than that in females for both ethnicities (93.5% vs. 69.6%;
      90.8% vs. 64.6%, respectively, p < 0.05). Among the Kazakh, the prevalence of
      hypertension was 35.1%, and the prevalence was higher in males than in females
      (44.3% vs. 28.1%, p < 0.001); 87.6% of the Kazakh individuals had H-type
      hypertension, and the prevalence was higher in males than in females (95.0% vs.
      80.0%, p < 0.05). In Uyghur, the prevalence of hypertension was 30.6%, and the
      prevalence was higher in males than in females (37.9% vs. 22.8%, p < 0.001);
      88.0% of the Uyghur individuals had H-type hypertension, and the prevalence was
      higher in males than in females (93.9% vs. 79.1%, p < 0.05). CONCLUSIONS: HHcy
      was found to be common among the Kazakh and Uyghur. The prevalences of HHcy and H
      type hypertension were high among both ethnicities and differed depending on
      gender and age. Community interventions should be conducted to improve public
      health conditions among the Kazakh and Uyghur in Xinjiang.

PMID- 25996891
TI  - Scoring system for periventricular leukomalacia in infants with congenital heart
      disease.
AB  - BACKGROUND: Currently two magnetic resonance imaging (MRI) methods have been used
      to assess periventricular leukomalacia (PVL) severity in infants with congenital
      heart disease: manual volumetric lesion segmentation and an observational
      categorical scale. Volumetric classification is labor intensive and the
      categorical scale is quick but unreliable. We propose the quartered point system
      (QPS) as a novel, intuitive, time-efficient metric with high interrater
      agreement. METHODS: QPS is an observational scale that asks the rater to score
      MRIs on the basis of lesion size, number, and distribution. Pre- and
      postoperative brain MRIs were obtained on term congenital heart disease infants.
      Three independent observers scored PVL severity using all three methods:
      volumetric segmentation, categorical scale, and QPS. RESULTS: One-hundred and
      thirty-five MRIs were obtained from 72 infants; PVL was seen in 48 MRIs.
      Volumetric measurements among the three raters were highly concordant (rhoc =
      0.94-0.96). Categorical scale severity scores were in poor agreement between
      observers (kappa = 0.17) and fair agreement with volumetrically determined
      severity (kappa = 0.26). QPS scores were in very good agreement between observers
      (kappa = 0.82) and with volumetric severity (kappa = 0.81). CONCLUSION: QPS
      minimizes training and sophisticated radiologic analysis and increases interrater
      reliability. QPS offers greater sensitivity to stratify PVL severity and has the
      potential to more accurately correlate with neurodevelopmental outcomes.

PMID- 25996892
TI  - Darbepoetin administration to neonates undergoing cooling for encephalopathy: a
      safety and pharmacokinetic trial.
AB  - BACKGROUND: Despite therapeutic hypothermia, neonates with encephalopathy (NE)
      have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable
      biological activity to erythropoietin, but has extended circulating half-life
      (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as
      adjunctive therapy to hypothermia. STUDY DESIGN: Thirty infants (n = 10/arm) >=36
      wk gestation undergoing therapeutic hypothermia for NE were randomized to receive
      placebo, Darbe low dose (2 MUg/kg), or high dose (10 MUg/kg) given intravenously
      within 12 h of birth (first dose/hypothermia condition) and at 7 d (second
      dose/normothermia condition). Adverse events were documented for 1 mo. Serum
      samples were obtained to characterize Darbe pharmacokinetics. RESULTS: Adverse
      events (hypotension, altered liver and renal function, seizures, and death) were
      similar to placebo and historical controls. Following the first Darbe dose at 2
      and 10 MUg/kg, t(1/2) was 24 and 32 h, and the area under the curve (AUC(inf))
      was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not
      significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t(1/2) was
      26 and 35 h, and AUC(inf) was 10,790 and 56,233 h*mU/ml*, respectively (*P <
      0.01). CONCLUSION: Darbe combined with hypothermia has similar safety profile to
      placebo with pharmacokinetics sufficient for weekly administration.

PMID- 25996893
TI  - Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat:
      characterization of a translational preclinical model.
AB  - BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity
      in survivors. Therapeutic hypothermia (TH) is the only available intervention,
      but the protection is incomplete. Preclinical studies of HIE/TH in the rodent
      have relied on the postnatal day (P) 7 rat whose brain approximates a 32-36 wk
      gestation infant, less relevant for these studies. We propose that HIE and TH in
      the term-equivalent P10 rat will be more translational. METHODS: P10-11 rat pups
      were subjected to unilateral hypoxia-ischemia (HI) and 4 h recovery in
      normothermic (N) or hypothermic (TH) conditions. Brain damage was assessed
      longitudinally at 24 h, 2 wk, and 12 wk. Motor function was assessed with the
      beam walk; recognition memory was measured by novel object recognition. RESULTS:
      Neuroprotection with TH was apparent at 2 and 12 wk in both moderately and
      severely damaged animals. TH improved motor function in moderate, but not severe,
      damage. Impaired object recognition occurred with severe damage with no evidence
      of protection of TH. CONCLUSION: This adaptation of the immature rat model of HI
      provides a reproducible platform to further study HIE/TH in which individual
      animals are followed up longitudinally to provide a useful translational
      preclinical model.

PMID- 25996895
TI  - Internal Derangements of Joints-Past, Present, and Future.
AB  - The past 50 years have transformed imaging of the joints. Whereas musculoskeletal
      imaging consisted predominantly of conventional radiography when Investigative
      Radiology was founded as a journal, the arrival of new imaging modalities, and
      above all, the introduction of magnetic resonance imaging, resulted in a paradigm
      shift: In addition to visualizing osseous structures, now the detailed depiction
      of soft tissue structures became part of routine clinical imaging and had a major
      impact on understanding pathophysiology and patient treatment. This article
      analyzes the patterns of innovation that were essential for the transformation of
      musculoskeletal radiology. Furthermore, state-of- the-art joint imaging is
      described through 9 key concepts, including both cutting-edge clinical
      applications as well as topics at the forefront of musculoskeletal research.
      Eventually, emerging trends are outlined that will likely shape musculoskeletal
      radiology in the next decades. 

PMID- 25996894
TI  - Molecular cloning, characterization and expression analysis of cathepsin O in
      silkworm Bombyx mori related to bacterial response.
AB  - Cathepsins are the main members of the cysteine family and play important roles
      in immune response in vertebrates. The Cathepsin O of Bombyx mori (BmCathepsin O)
      was cloned from the hemocytes by the rapid amplification of cDNA ends (RACE). The
      genomic DNA was 6131bp long with a total of six exons and five introns. Its pre
      mRNA was spliced to generate two spliceosomes. By comparisons with other reported
      cathepsins O, it was concluded that the identity between them ranged from 29 to
      39%. Expression analysis indicated that BmCathepsin O was specific-expressed in
      hemocytes, and highly expressed at the 4th molting and metamorphosis stages.
      Immunofluorescence assay and qRT-PCR showed that BmCathepsin O was expressed in
      granulocytes and plasmatocytes. Interestingly, BmCathepsin O was significantly up
      regulated after stimulated by 20-hydroxyecdysone (20-E) in vivo, which suggested
      that BmCathepsin O may be regulated by 20E. Moreover, activation of BmCathepsin O
      was also observed in hemocytes challenged by Escherichia coli, indicating its
      potential involvement in the innate immune system of silkworm, B. mori. In
      summary, our studies provide a new insight into the functional features of
      Cathepsin O.

PMID- 25996896
TI  - Profusion of Opacities in Simple Coal Worker's Pneumoconiosis Is Associated With
      Reduced Lung Function.
AB  - BACKGROUND: A large body of evidence demonstrates dose-response relationships of
      cumulative coal mine dust exposure with lung function impairment and with small
      opacity profusion. However, medical literature generally holds that simple coal
      worker's pneumoconiosis (CWP) is not associated with lung function impairment.
      This study examines the relationship between small-opacity profusion and lung
      function in US underground coal miners with simple CWP. METHODS: Miners were
      examined during 2005 to 2013 as part of the Enhanced Coal Workers' Health
      Surveillance Program. Work histories were obtained, and chest radiographs and
      spirometry were administered. Lung parenchymal abnormalities consistent with CWP
      were classified according to International Labor Organization guidelines, and
      reference values for FEV1 and FVC were calculated using reference equations
      derived from the third National Health and Nutrition Examination Survey.
      Differences in lung function were evaluated by opacity profusion, and regression
      models were fit to characterize associations between profusion and lung function.
      RESULTS: A total of 8,230 miners were eligible for analysis; 269 had category 1
      or 2 simple CWP. Decrements in FEV1 % predicted were nearly consistent across
      profusion subcategories. Clear decrements in FVC % predicted and FEV1/FVC were
      also observed, although these were less consistent. Controlling for smoking
      status, BMI, and mining tenure, each 1-unit subcategory increase in profusion was
      associated with decreases of 1.5% (95% CI, 1.0%-1.9%), 1.0% (95% CI, 0.6%-1.3%),
      and 0.6% (95% CI, 0.4%-0.8%) in FEV1 % predicted, FVC % predicted, and FEV1/FVC,
      respectively. CONCLUSIONS: We observed progressively lower lung function across
      the range of small-opacity profusion. These findings address a long-standing
      question in occupational medicine and point to the importance of medical
      surveillance and respiratory disease prevention in this workforce.

PMID- 25996897
TI  - Polyproteins in structural biology.
AB  - Polyproteins are chains of covalently conjoined smaller proteins that occur in
      nature as versatile means to organize the proteome of viruses including HIV.
      During maturation, viral polyproteins are typically cleaved into the constituent
      proteins with different biological functions by highly specific proteases, and
      structural analyses at defined stages of this maturation process can provide
      clues for antiviral intervention strategies. Recombinant polyproteins that use
      similar mechanisms are emerging as powerful tools for producing hitherto
      inaccessible protein targets such as the influenza polymerase, for high
      resolution structure determination by X-ray crystallography. Conversely, covalent
      linking of individual protein subunits into single polypeptide chains are
      exploited to overcome sample preparation bottlenecks. Moreover, synthetic
      polyproteins provide a promising tool to dissect dynamic folding of polypeptide
      chains into three-dimensional architectures in single-molecule structure analysis
      by atomic force microscopy (AFM). The recent use of natural and synthetic
      polyproteins in structural biology and major achievements are highlighted in this
      contribution. 

PMID- 25996898
TI  - Ethylene suppresses tomato (Solanum lycopersicum) fruit set through modification
      of gibberellin metabolism.
AB  - Fruit set in angiosperms marks the transition from flowering to fruit production
      and a commitment to seed dispersal. Studies with Solanum lycopersicum (tomato)
      fruit have shown that pollination and subsequent fertilization induce the
      biosynthesis of several hormones, including auxin and gibberellins (GAs), which
      stimulate fruit set. Circumstantial evidence suggests that the gaseous hormone
      ethylene may also influence fruit set, but this has yet to be substantiated with
      molecular or mechanistic data. Here, we examined fruit set at the biochemical and
      genetic levels, using hormone and inhibitor treatments, and mutants that affect
      auxin or ethylene signaling. The expression of system-1 ethylene biosynthetic
      genes and the production of ethylene decreased during pollination-dependent fruit
      set in wild-type tomato and during pollination-independent fruit set in the auxin
      hypersensitive mutant iaa9-3. Blocking ethylene perception in emasculated
      flowers, using either the ethylene-insensitive Sletr1-1 mutation or 1
      methylcyclopropene (1-MCP), resulted in elongated parthenocarpic fruit and
      increased cell expansion, whereas simultaneous treatment with the GA biosynthesis
      inhibitor paclobutrazol (PAC) inhibited parthenocarpy. Additionally, the
      application of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC)
      to pollinated ovaries reduced fruit set. Furthermore, Sletr1-1 parthenocarpic
      fruits did not exhibit increased auxin accumulation, but rather had elevated
      levels of bioactive GAs, most likely reflecting an increase in transcripts
      encoding the GA-biosynthetic enzyme SlGA20ox3, as well as a reduction in the
      levels of transcripts encoding the GA-inactivating enzymes SlGA2ox4 and SlGA2ox5.
      Taken together, our results suggest that ethylene plays a role in tomato fruit
      set by suppressing GA metabolism. 

PMID- 25996899
TI  - Temporal predictability enhances judgements of causality in elemental causal
      induction from both observation and intervention.
AB  - When the temporal interval or delay separating cause and effect is consistent
      over repeated instances, it becomes possible to predict when the effect will
      follow from the cause, hence temporal predictability serves as an appropriate
      term for describing consistent cause-effect delays. It has been demonstrated that
      in instrumental action-outcome learning tasks, enhancing temporal predictability
      by holding the cause-effect interval constant elicits higher judgements of
      causality compared to conditions involving variable temporal intervals. Here, we
      examine whether temporal predictability exerts a similar influence when causal
      learning takes place through observation rather than intervention through
      instrumental action. Four experiments demonstrated that judgements of causality
      were higher when the temporal interval was constant than when it was variable,
      and that judgements declined with increasing variability. We further found that
      this beneficial effect of predictability was stronger in situations where the
      effect base-rate was zero (Experiments 1 and 3). The results therefore clearly
      indicate that temporal predictability enhances impressions of causality, and that
      this effect is robust and general. Factors that could mediate this effect are
      discussed. 

PMID- 25996900
TI  - Self-assembly of [3]catenanes and a [4]molecular necklace based on a
      cryptand/paraquat recognition motif.
AB  - Hierarchical self-assembly centered on metallacyclic scaffolds greatly
      facilitates the construction of mechanically interlocked structures. The
      formation of two [3]catenanes and one [4]molecular necklace is presented by
      utilizing the orthogonality of coordination-driven self-assembly and crown ether
      based cryptand/paraquat derivative complexation. The threaded [3]catenanes and
      [4]molecular necklace were fabricated by using ten and nine total molecular
      components, respectively, from four and three unique species in solution,
      respectively. In all cases single supramolecular ensembles were obtained,
      attesting to the high degree of structural complexity made possible via self
      assembly approaches. 

PMID- 25996902
TI  - JBP485 promotes tear and mucin secretion in ocular surface epithelia.
AB  - Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface,
      is one of the most common ocular disorders. Tear film contains ocular mucins and
      is essential for maintaining the homeostasis of the wet ocular surface. Since
      there are a limited number of clinical options for the treatment of DES,
      additional novel treatments are needed to improve the clinical results. In this
      study, we found that placental extract-derived dipeptide (JBP485) clearly
      promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit
      conjunctival epithelium. JBP485 also elevated the expression level of cell
      surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer
      tear test results indicated that JBP485 induced tear secretion in the rabbit
      model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse
      dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and
      aqueous tear secretion in rabbit ocular surface epithelium and has the potential
      to be used as a novel treatment for DES. 

PMID- 25996904
TI  - Yolk@Shell Nanoarchitecture of Au@r-GO/TiO2 Hybrids as Powerful Visible Light
      Photocatalysts.
AB  - Yolk@shell nanostructures of Au@r-GO/TiO2 with mesoporous shells were prepared by
      a sol-gel coating process sequentially with GO and TiO2 on Au/SiO2 core/shell
      spheres, followed by calcination and template removal, where the silica
      interlayer acts as a template not only to produce the void space but also to
      promote the coating of the r-GO and TiO2 layer. The evaluation of visible light
      photocatalytic activities in dye decomposition and water-splitting H2 production
      demonstrated their superior photocatalytic performance, which indicates their
      potential as powerful photocatalysts. 

PMID- 25996903
TI  - Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene
      glycol) for Drug Delivery and in Situ Cell Encapsulation.
AB  - Polymers or hydrogels containing modified cyclodextrin (CD) are highly useful in
      drug delivery applications, as CD is a cytocompatible amphiphilic molecule that
      can complex with a variety of hydrophobic drugs. Here, we designed modular
      photoclick thiol-ene hydrogels from derivatives of betaCD and poly(ethylene
      glycol) (PEG), including betaCD-allylether (betaCD-AE), betaCD-thiol (betaCD-SH),
      PEG-thiol (PEGSH), and PEG-norbornene (PEGNB). Two types of CD-PEG hybrid
      hydrogels were prepared using radical-mediated thiol-ene photoclick reactions.
      Specifically, thiol-allylether hydrogels were formed by reacting multiarm PEGSH
      and betaCD-AE, and thiol-norbornene hydrogels were formed by cross-linking betaCD
      SH and multiarm PEGNB. We characterized the properties of these two types of
      thiol-ene hydrogels, including gelation kinetics, gel fractions, hydrolytic
      stability, and cytocompatibility. Compared with thiol-allylether hydrogels, thiol
      norbornene photoclick reaction formed hydrogels with faster gelation kinetics at
      equivalent macromer contents. Using curcumin, an anti-inflammatory and anticancer
      hydrophobic molecule, we demonstrated that CD-cross-linked PEG-based hydrogels,
      when compared with pure PEG-based hydrogels, afforded higher drug loading
      efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-cross
      linked hydrogels were evaluated by in situ encapsulation of radical sensitive
      pancreatic MIN6 beta-cells. All formulations and cross-linking conditions tested
      were cytocompatible for cell encapsulation. Furthermore, hydrogels cross-linked
      by betaCD-SH showed enhanced cell proliferation and insulin secretion as compared
      to gels cross-linked by either dithiothreitol (DTT) or betaCD-AE, suggesting the
      profound impact of both macromer compositions and gelation chemistry on cell fate
      in chemically cross-linked hydrogels.

PMID- 25996905
TI  - Cirrhotic liver: What's that nodule? The LI-RADS approach.
AB  - The Liver Imaging Reporting and Data System (LI-RADS) is an American College of
      Radiology (ACR)-endorsed diagnostic system of standardized terminology,
      interpretation, and reporting for imaging examinations of the liver in patients
      at high risk for hepatocellular carcinoma (HCC). LI-RADS assigns a category to
      observations in the liver indicating the likelihood of benignity or HCC. LI-RADS
      categories include LR-1: Definitely Benign, LR-2: Probably Benign, LR-3:
      Intermediate Probability for HCC, LR-4: Probably HCC, LR-5: Definite HCC, LR-5V:
      Definite HCC with Tumor in Vein, LR-Treated: Treated HCC, LR-M Probable
      Malignancy, not specific for HCC. This article reviews the types of nodules seen
      in the cirrhotic liver, examines core LI-RADS concepts and definitions, and
      utilizes the LI-RADS v2014 algorithm to categorize representative observations
      depicted at magnetic resonance imaging in a case-based approach.

PMID- 25996906
TI  - Bi(OTf)3-Catalyzed Multicomponent alpha-Amidoalkylation Reactions.
AB  - A bismuth(III) triflate catalyzed three-component synthesis of alpha-substituted
      amides starting from amides, aldehydes, and (hetero)arenes is reported. The
      reaction has a broad substrate scope, encompassing formaldehyde as well as aryl
      and alkyl aldehydes. Low catalyst loadings are required, and water is formed as
      the only side product. The scope and limitation of this method will be discussed.

PMID- 25996907
TI  - A colourful clock.
AB  - Circadian rhythms are an essential property of life on Earth. In mammals, these
      rhythms are coordinated by a small set of neurons, located in the suprachiasmatic
      nuclei (SCN). The environmental light/dark cycle synchronizes (entrains) the SCN
      via a distinct pathway, originating in a subset of photosensitive retinal
      ganglion cells (pRGCs) that utilize the photopigment melanopsin (OPN4). The pRGCs
      are also innervated by rods and cones and, so, are both endogenously and
      exogenously light sensitive. Accumulating evidence has shown that the circadian
      system is sensitive to ultraviolet (UV), blue, and green wavelengths of light.
      However, it was unclear whether colour perception itself can help entrain the
      SCN. By utilizing both behavioural and electrophysiological recording techniques,
      Walmsley and colleagues show that multiple photic channels interact and enhance
      the capacity of the SCN to synchronize to the environmental cycle. Thus,
      entrainment of the circadian system combines both environmental irradiance and
      colour information to ensure that internal and external time are appropriately
      aligned. 

PMID- 25996908
TI  - Effects of applying molasses, lactic acid bacteria and propionic acid on
      fermentation quality, aerobic stability and in vitro gas production of total
      mixed ration silage prepared with oat-common vetch intercrop on the Tibetan
      Plateau.
AB  - BACKGROUND: The objective of this study was to investigate the effect of
      molasses, lactic acid bacteria and propionic acid on the fermentation quality,
      aerobic stability and in vitro gas production of total mixed ration (TMR) silage
      prepared with oat-common vetch intercrop on the Tibetan plateau. TMR (436 g kg(
      1) dry matter (DM)) was ensiled with six experimental treatments: (1) no
      additives (control); (2) molasses (M); (3) an inoculant (Lactobacillus plantarum)
      (L); (4) propionic acid (P); (5) molasses + propionic acid (MP); (6) inoculant +
      propionic acid (LP). RESULT: All silages were well preserved with low pH (< 4.19)
      and NH3-N contents, and high lactic acid contents after ensiling for 45 days. L
      and PL silages underwent a more efficient fermentation than silages without L. P
      and MP silages inhibited lactic acid production. Under aerobic conditions, M and
      L silage reduced aerobic stability for 15 and 74 h, respectively. All silages
      that had propionic acid in their treatments markedly (P < 0.05) improved the
      aerobic stability. After 72 h incubation, all additives treatments increased (P <
      0.05) the 72 h cumulative gas production and in vitro DM digestibility (IVDMD) as
      compared with the control. L treatment decreased (P < 0.05) in vitro neutral
      detergent fibre degradability. CONCLUSIONS: Our findings show that TMR prepared
      with oat-common vetch intercrop can be well preserved. Although propionic acid is
      compatible with lactic acid bacteria, and when used together, they had minor
      effects on fermentation, aerobic stability and in vitro digestibility of TMR
      silage prepared with oat-common vetch intercrop.

PMID- 25996909
TI  - Zika Virus in an American Recreational Traveler.
AB  - We report the case of a 48-year-old American traveler who presented to our clinic
      with diffuse rash, malaise, fatigue, fever, arthralgia, low back pain, and
      bilateral exudative conjunctivitis. The patient had an extensive vaccination and
      travel history: most notable for prior receipt of yellow fever vaccine; extensive
      travel or residence in areas endemic for dengue, chikungunya, and West Nile
      virus; and recent travel to French Polynesia. Clinical and laboratory findings
      were consistent with Zika virus (ZIKV) infection. Our report highlights the need
      to include ZIKV in the differential diagnosis, especially in febrile patients
      with a rash returning from endemic areas. 

PMID- 25996910
TI  - How Does Photoreceptor UVR8 Perceive a UV-B Signal?
AB  - UVR8 is the only known plant photoreceptor that mediates light responses to UV-B
      (280-315 nm) of the solar spectrum. UVR8 perceives a UV-B signal via light
      induced dimer dissociation, which triggers a wide range of cellular responses
      involved in photomorphogenesis and photoprotection. Two recent crystal structures
      of Arabidopsis thaliana UVR8 (AtUVR8) have revealed unusual clustering of UV-B
      absorbing Trp pigments at the dimer interface and provided a structural framework
      for further mechanistic investigation. This review summarizes recent advances in
      spectroscopic, computational and crystallographic studies on UVR8 that are
      directed toward full understanding of UV-B perception at the molecular level. 

PMID- 25996911
TI  - Hydrogen and oxygen stable isotope fractionation in body fluid compartments of
      dairy cattle according to season, farm, breed, and reproductive stage.
AB  - Environmental temperature affects water turnover and isotope fractionation by
      causing water evaporation from the body in mammals. This may lead to
      rearrangement of the water stable isotope equilibrium in body fluids. We propose
      an approach to detect possible variations in the isotope ratio in different body
      fluids on the basis of different homoeothermic adaptations in varying
      reproductive stages. Three different reproductive stages (pregnant heifer,
      primiparous lactating cow, and pluriparous lactating cow) of two dairy cattle
      breeds (Italian Friesian and Modenese) were studied in winter and summer. Blood
      plasma, urine, faecal water, and milk were sampled and the isotope ratios of H
      (2H/1H) and O (18O/16O) were determined. Deuterium excess and isotope
      fractionation factors were calculated for each passage from plasma to faeces,
      urine and milk. The effects of the season, reproductive stages and breed on
      delta2H and delta18O were significant in all the fluids, with few exceptions.
      Deuterium excess was affected by season in all the analysed fluids. The
      correlations between water isotope measurements in bovine body fluids ranged
      between 0.6936 (urine-milk) and 0.7848 (urine-plasma) for delta2H, and between
      0.8705 (urine-milk) and 0.9602 (plasma-milk) for delta18O. The increase in both
      isotopic delta values in all body fluids during summer is representative of a
      condition in which fractionation took place as a consequence of a different ratio
      between ingested and excreted water, which leads to an increased presence of the
      heavy isotopes. The different body water turnover between adult lactating cattle
      and non-lactating heifers was confirmed by the higher isotopic delta for the
      latter, with a shift in the isotopic equilibrium towards values more distant from
      those of drinking water. 

PMID- 25996913
TI  - Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral
      Immunity.
AB  - Immunity to non-cerebral severe malaria is estimated to occur within 1-2
      infections in areas of endemic transmission for Plasmodium falciparum. Yet,
      nearly 20% of infected children die annually as a result of severe malaria.
      Multiple risk factors are postulated to exacerbate malarial disease, one being co
      infections with other pathogens. Children living in Sub-Saharan Africa are
      seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing
      overlaps with the waning of protective maternal antibodies and susceptibility to
      primary Plasmodium infection. However, the impact of acute EBV infection on the
      generation of anti-malarial immunity is unknown. Using well established mouse
      models of infection, we show here that acute, but not latent murine
      gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral
      response to a secondary malaria infection. Importantly, this resulted in the
      transformation of a non-lethal P. yoelii XNL infection into a lethal one; an
      outcome that is correlated with a defect in the maintenance of germinal center B
      cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have
      identified the MHV68 M2 protein as an important virus encoded protein that can:
      (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii)
      plays a critical role in the observed suppression of anti-malarial humoral
      responses in the setting of co-infection. Notably, co-infection with an M2-null
      mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data
      demonstrates that an acute gammaherpesvirus infection can negatively impact the
      development of an anti-malarial immune response. This suggests that acute
      infection with EBV should be investigated as a risk factor for non-cerebral
      severe malaria in young children living in areas endemic for Plasmodium
      transmission. 

PMID- 25996914
TI  - Clustering and negative feedback by endocytosis in planar cell polarity signaling
      is modulated by ubiquitinylation of prickle.
AB  - The core components of the planar cell polarity (PCP) signaling system, including
      both transmembrane and peripheral membrane associated proteins, form asymmetric
      complexes that bridge apical intercellular junctions. While these can assemble in
      either orientation, coordinated cell polarization requires the enrichment of
      complexes of a given orientation at specific junctions. This might occur by both
      positive and negative feedback between oppositely oriented complexes, and
      requires the peripheral membrane associated PCP components. However, the
      molecular mechanisms underlying feedback are not understood. We find that the E3
      ubiquitin ligase complex Cullin1(Cul1)/SkpA/Supernumerary limbs(Slimb) regulates
      the stability of one of the peripheral membrane components, Prickle (Pk). Excess
      Pk disrupts PCP feedback and prevents asymmetry. We show that Pk participates in
      negative feedback by mediating internalization of PCP complexes containing the
      transmembrane components Van Gogh (Vang) and Flamingo (Fmi), and that
      internalization is activated by oppositely oriented complexes within clusters. Pk
      also participates in positive feedback through an unknown mechanism promoting
      clustering. Our results therefore identify a molecular mechanism underlying
      generation of asymmetry in PCP signaling. 

PMID- 25996917
TI  - Robust and Reproducible Quantification of the Extent of Chest Radiographic
      Abnormalities (And It's Free!).
AB  - RATIONALE: Objective, reproducible quantification of the extent of abnormalities
      seen on a chest radiograph would improve the user-friendliness of a previously
      proposed severity scoring system for pulmonary tuberculosis and could be helpful
      in monitoring response to therapy, including in clinical trials. METHODS: In this
      study we report the development and evaluation of a simple tool using free image
      editing software (GIMP) to accurately and reproducibly quantify the area of
      affected lung on the chest radiograph of tuberculosis patients. As part of a
      pharmacokinetic study in Lima, Peru, a chest radiograph was performed on patients
      with pulmonary tuberculosis and this was subsequently photographed using a
      digital camera. The GIMP software was used by two independent and trained readers
      to estimate the extent of affected lung (expressed as a percentage of total lung
      area) in each radiograph and the resulting radiographic SCORE. RESULTS: 56 chest
      radiographs were included in the reading analysis. The Intraclass correlation
      coefficient (ICC) between the 2 observers was 0.977 (p<0.001) for the area of
      lung affected and was 0.955 (p<0.001) for the final score; and the kappa
      coefficient of Interobserver agreement for both the area of lung affected and the
      score were 0.9 (p<0.001) and 0.86 (p<0.001) respectively. CONCLUSIONS: This high
      level of between-observer agreement suggests that this freely available software
      could constitute a simple and useful tool for robust evaluation of individual and
      serial chest radiographs.

PMID- 25996916
TI  - Blood-Stage Parasitaemia and Age Determine Plasmodium falciparum and P. vivax
      Gametocytaemia in Papua New Guinea.
AB  - A better understanding of human-to-mosquito transmission is crucial to control
      malaria. In order to assess factors associated with gametocyte carriage, 2083
      samples were collected in a cross-sectional survey in Papua New Guinea.
      Plasmodium species were detected by light microscopy and qPCR and gametocytes by
      detection of pfs25 and pvs25 mRNA transcripts by reverse-transcriptase PCR (qRT
      PCR). The parasite prevalence by PCR was 18.5% for Plasmodium falciparum and
      13.0% for P. vivax. 52.5% of all infections were submicroscopic. Gametocytes were
      detected in 60% of P. falciparum-positive and 51% of P. vivax-positive samples.
      Each 10-fold increase in parasite density led to a 1.8-fold and 3.3-fold increase
      in the odds of carrying P. falciparum and P. vivax gametocytes. Thus the
      proportion of gametocyte positive and gametocyte densities was highest in young
      children carrying high asexual parasite densities and in symptomatic individuals.
      Dilution series of gametocytes allowed absolute quantification of gametocyte
      densities by qRT-PCR and showed that pvs25 expression is 10-20 fold lower than
      pfs25 expression. Between 2006 and 2010 parasite prevalence in the study site has
      decreased by half. 90% of the remaining infections were asymptomatic and likely
      constitute an important reservoir of transmission. However, mean gametocyte
      densities were low (approx. 1-2 gametocyte/MUL) and it remains to be determined
      to what extent low-density gametocyte positive individuals are infective to
      mosquitos. 

PMID- 25996915
TI  - Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype
      Phenotype Correlations in 187 Subjects from the US AHCF Registry.
AB  - Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting
      function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2
      recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K
      cohort. We performed mutation analysis and retrospective genotype-phenotype
      correlations in all eligible patients with AHC enrolled in the US AHC Foundation
      registry from 1997-2012. Clinical data were abstracted from standardized
      caregivers' questionnaires and medical records and confirmed by expert
      clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing,
      and compared phenotypes within and between 4 groups of subjects, those with
      D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous
      ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31
      (91%) are missense, and 16 (47%) had not been previously reported. Concordant
      with prior studies, more than 2/3 of all mutations are clusteredin exons 17 and
      18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K(26%) and 11 had
      G947R (8%) mutations [corrected].Patients with an E815K mutation demonstrate an
      earlier age of onset, more severe motor impairment and a higher prevalence of
      status epilepticus. This study further expands the number and spectrum of ATP1A3
      mutations associated with AHC and confirms a more deleterious effect of the E815K
      mutation on selected neurologic outcomes. However, the complexity of the disorder
      and the extensive phenotypic variability among subgroups merits caution and
      emphasizes the need for further studies.

PMID- 25996918
TI  - Flavourzyme, an Enzyme Preparation with Industrial Relevance: Automated Nine-Step
      Purification and Partial Characterization of Eight Enzymes.
AB  - Flavourzyme is sold as a peptidase preparation from Aspergillus oryzae. The
      enzyme preparation is widely and diversely used for protein hydrolysis in
      industrial and research applications. However, detailed information about the
      composition of this mixture is still missing due to the complexity. The present
      study identified eight key enzymes by mass spectrometry and partially by activity
      staining on native polyacrylamide gels or gel zymography. The eight enzymes
      identified were two aminopeptidases, two dipeptidyl peptidases, three
      endopeptidases, and one alpha-amylase from the A. oryzae strain ATCC 42149/RIB 40
      (yellow koji mold). Various specific marker substrates for these Flavourzyme
      enzymes were ascertained. An automated, time-saving nine-step protocol for the
      purification of all eight enzymes within 7 h was designed. Finally, the purified
      Flavourzyme enzymes were biochemically characterized with regard to pH and
      temperature profiles and molecular sizes. 

PMID- 25996920
TI  - A Highly Efficient Gene Expression Programming (GEP) Model for Auxiliary
      Diagnosis of Small Cell Lung Cancer.
AB  - BACKGROUND: Lung cancer is an important and common cancer that constitutes a
      major public health problem, but early detection of small cell lung cancer can
      significantly improve the survival rate of cancer patients. A number of serum
      biomarkers have been used in the diagnosis of lung cancers; however, they exhibit
      low sensitivity and specificity. METHODS: We used biochemical methods to measure
      blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na+, Cl-,
      carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small
      cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155
      normal controls. A gene expression programming (GEP) model and Receiver Operating
      Characteristic (ROC) curves incorporating these biomarkers was developed for the
      auxiliary diagnosis of SCLC. RESULTS: After appropriate modification of the
      parameters, the GEP model was initially set up based on a training set of 115
      SCLC patients and 125 normal controls for GEP model generation. Then the GEP was
      applied to the remaining 60 subjects (the test set) for model validation. GEP
      successfully discriminated 281 out of 300 cases, showing a correct classification
      rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the
      training and test sets, respectively. Another GEP model incorporating four
      biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection
      sensitivity than the GEP model, including six biomarkers. We repeat the models on
      artificial neural network (ANN), and our results showed that the accuracy of GEP
      models were higher than that in ANN. GEP model incorporating six serum biomarkers
      performed by NSCLC patients and normal controls showed low accuracy than SCLC
      patients and was enough to prove that the GEP model is suitable for the SCLC
      patients. CONCLUSION: We have developed a GEP model with high sensitivity and
      specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential
      for the wide use for detection of SCLC in less developed regions.

PMID- 25996919
TI  - Lactate up-regulates the expression of lactate oxidation complex-related genes in
      left ventricular cardiac tissue of rats.
AB  - BACKGROUND: Besides its role as a fuel source in intermediary metabolism, lactate
      has been considered a signaling molecule modulating lactate-sensitive genes
      involved in the regulation of skeletal muscle metabolism. Even though the flux of
      lactate is significantly high in the heart, its role on regulation of cardiac
      genes regulating lactate oxidation has not been clarified yet. We tested the
      hypothesis that lactate would increase cardiac levels of reactive oxygen species
      and up-regulate the expression of genes related to lactate oxidation complex.
      METHODS/PRINCIPAL FINDINGS: Isolated hearts from male adult Wistar rats were
      perfused with control, lactate or acetate (20mM) added Krebs-Henseleit solution
      during 120 min in modified Langendorff apparatus. Reactive oxygen species (O2?
      /H2O2) levels, and NADH and NADPH oxidase activities (in enriched microsomal or
      plasmatic membranes, respectively) were evaluated by fluorimetry while SOD and
      catalase activities were evaluated by spectrophotometry. mRNA levels of lactate
      oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1alpha
      and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also
      evaluated. Hemodynamic parameters were acquired during the experiment. The key
      findings of this work were that lactate elevated cardiac NADH oxidase activity
      but not NADPH activity. This response was associated with increased cardiac O2?
      /H2O2 levels and up-regulation of MCT1, MCT4, LDH and PGC1alpha with no changes
      in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased
      NRF-2 nuclear expression and SOD activity probably as counter-regulatory
      responses to increased O2?-/H2O2. CONCLUSIONS: Our results provide evidence for
      lactate-induced up-regulation of lactate oxidation complex associated with
      increased NADH oxidase activity and cardiac O2?-/H2O2 driving to an anti-oxidant
      response. These results unveil lactate as an important signaling molecule
      regulating components of the lactate oxidation complex in cardiac muscle.

PMID- 25996921
TI  - The filament sensor for near real-time detection of cytoskeletal fiber
      structures.
AB  - A reliable extraction of filament data from microscopic images is of high
      interest in the analysis of acto-myosin structures as early morphological markers
      in mechanically guided differentiation of human mesenchymal stem cells and the
      understanding of the underlying fiber arrangement processes. In this paper, we
      propose the filament sensor (FS), a fast and robust processing sequence which
      detects and records location, orientation, length, and width for each single
      filament of an image, and thus allows for the above described analysis. The
      extraction of these features has previously not been possible with existing
      methods. We evaluate the performance of the proposed FS in terms of accuracy and
      speed in comparison to three existing methods with respect to their limited
      output. Further, we provide a benchmark dataset of real cell images along with
      filaments manually marked by a human expert as well as simulated benchmark
      images. The FS clearly outperforms existing methods in terms of computational
      runtime and filament extraction accuracy. The implementation of the FS and the
      benchmark database are available as open source. 

PMID- 25996922
TI  - F-formation detection: individuating free-standing conversational groups in
      images.
AB  - Detection of groups of interacting people is a very interesting and useful task
      in many modern technologies, with application fields spanning from video
      surveillance to social robotics. In this paper we first furnish a rigorous
      definition of group considering the background of the social sciences: this
      allows us to specify many kinds of group, so far neglected in the Computer Vision
      literature. On top of this taxonomy we present a detailed state of the art on the
      group detection algorithms. Then, as a main contribution, we present a brand new
      method for the automatic detection of groups in still images, which is based on a
      graph-cuts framework for clustering individuals; in particular, we are able to
      codify in a computational sense the sociological definition of F-formation, that
      is very useful to encode a group having only proxemic information: position and
      orientation of people. We call the proposed method Graph-Cuts for F-formation
      (GCFF). We show how GCFF definitely outperforms all the state of the art methods
      in terms of different accuracy measures (some of them are brand new),
      demonstrating also a strong robustness to noise and versatility in recognizing
      groups of various cardinality. 

PMID- 25996924
TI  - Correction: open labware: 3-d printing your own lab equipment.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.1002086.]. 

PMID- 25996925
TI  - Abstracts: International Society for Aerosols in Medicine e.V. 20th ISAM Congress
      Munich Holiday Inn-City Center, Germany May 30-June 3, 2015.

PMID- 25996923
TI  - The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial
      Cells and Disrupts Epithelial Monolayer Integrity.
AB  - Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and impair
      essential functions of eukaryotic cells. It has been previously reported that
      Neisseria meningitidis possesses an ADP-ribosyltransferase enzyme, NarE,
      retaining the capacity to hydrolyse NAD and to transfer ADP-ribose moiety to
      arginine residues in target acceptor proteins. Here we show that upon
      internalization into human epithelial cells, NarE gains access to the cytoplasm
      and, through its ADP-ribosylating activity, targets host cell proteins. Notably,
      we observed that these events trigger the disruption of the epithelial monolayer
      integrity and the activation of the apoptotic pathway. Overall, our findings
      provide, for the first time, evidence for a biological activity of NarE on host
      cells, suggesting its possible involvement in Neisseria pathogenesis. 

PMID- 25996926
TI  - Burden and Correlates of HIV among Men Who Have Sex with Men in West Bengal,
      India: Analysis of Sentinel Surveillance Data.
AB  - BACKGROUND: Little is known about the socio-behavioral risk factors for HIV
      acquisition among hard-to-reach men who have sex with men (MSM) population in
      India, particularly from the densely populated eastern part. Thus to measure the
      burden and correlates of HIV among MSM in West Bengal state of eastern India, a
      cross-sectional analysis of the national HIV Sentinel Surveillance (HSS) data was
      conducted. METHODS: In 2011, between July and September, involving all sentinel
      sites of the state, 1237 consenting MSM were anonymously interviewed and tested
      for HIV following national guidelines. Using a short, structured questionnaire,
      information was collected on socio-behavioral factors along with sexual practices
      and was analyzed to determine burden of HIV and the role of its socio-behavioral
      correlates on HIV acquisition. RESULTS: Among participants, mean age was 23.4
      years, 44.55% were "Kothis" (usually receptive partner) and 25.1% admitted
      receiving money for sex with man. HIV sero-positivity was 5.09%. Using logistic
      regression method, for both bivariate and multivariate (with saturated model)
      analyses, transport-workers [adjusted odds ratio (AOR)=8.95, 95% confidence
      interval (95%CI): 1.09-73.71), large business-owners/self-employed (AOR=8.46,
      95%CI: 1.25-57.49), small business-owners/cultivators (AOR=7.90, 95%CI: 1.67
      37.38), those who visited the sentinel site for official purposes (AOR=7.60,
      95%CI: 1.21-47.83) and paying money for having sex with men (AOR=3.03, 95%CI:
      1.10-8.33) were strongly associated with higher HIV sero-positivity with than
      their counterparts. Using the parsimonious model for multivariate analysis,
      Kothis (AOR=4.64, 95%CI: 1.03-20.89), paying (AOR=2.96, 95%CI: 1.15-7.58) or
      receiving (AOR=2.06, 95%CI: 1.06-3.99) money for having sex with a man were
      associated with higher risk of HIV. CONCLUSIONS: Focused intervention targeting
      the high risk MSM subgroups including Kothis, transport-workers, business
      owners/self-employed and those who exchanged money for having sex with men,
      seemed to be the need of the hour for preventing the spread of HIV infection
      within and from this understudied population.

PMID- 25996929
TI  - Correction: synthesis and biological properties of fungal glucosylceramide.

PMID- 25996928
TI  - Outcome discrepancies and selective reporting: impacting the leading journals?
AB  - BACKGROUND: Selective outcome reporting of either interesting or positive
      research findings is problematic, running the risk of poorly-informed treatment
      decisions. We aimed to assess the extent of outcome and other discrepancies and
      possible selective reporting between registry entries and published reports among
      leading medical journals. METHODS: Randomized controlled trials published over a
      6-month period from July to December 31st, 2013, were identified in five high
      impact medical journals: The Lancet, British Medical Journal, New England Journal
      of Medicine, Annals of Internal Medicine and Journal of American Medical
      Association were obtained. Discrepancies between published studies and registry
      entries were identified and related to factors including registration timing,
      source of funding and presence of statistically significant results. RESULTS:
      Over the 6-month period, 137 RCTs were found. Of these, 18% (n = 25) had
      discrepancies related to primary outcomes with the primary outcome changed in 15%
      (n = 20). Moreover, differences relating to non-primary outcomes were found in
      64% (n = 87) with both omission of pre-specified non-primary outcomes (39%) and
      introduction of new non-primary outcomes (44%) common. No relationship between
      primary or non-primary outcome change and registration timing (prospective or
      retrospective; P = 0.11), source of funding (P = 0.92) and presence of
      statistically significant results (P = 0.92) was found. CONCLUSIONS:
      Discrepancies between registry entries and published articles for primary and non
      primary outcomes were common among trials published in leading medical journals.
      Novel approaches are required to address this problem.

PMID- 25996927
TI  - Altered Proteome of Burkholderia pseudomallei Colony Variants Induced by Exposure
      to Human Lung Epithelial Cells.
AB  - Burkholderia pseudomallei primary diagnostic cultures demonstrate colony
      morphology variation associated with expression of virulence and adaptation
      proteins. This study aims to examine the ability of B. pseudomallei colony
      variants (wild type [WT] and small colony variant [SCV]) to survive and replicate
      intracellularly in A549 cells and to identify the alterations in the protein
      expression of these variants, post-exposure to the A549 cells. Intracellular
      survival and cytotoxicity assays were performed followed by proteomics analysis
      using two-dimensional gel electrophoresis. B. pseudomallei SCV survive longer
      than the WT. During post-exposure, among 259 and 260 protein spots of SCV and WT,
      respectively, 19 were differentially expressed. Among SCV post-exposure up
      regulated proteins, glyceraldehyde 3-phosphate dehydrogenase, fructose
      bisphosphate aldolase (CbbA) and betaine aldehyde dehydrogenase were associated
      with adhesion and virulence. Among the down-regulated proteins, enolase (Eno) is
      implicated in adhesion and virulence. Additionally, post-exposure expression
      profiles of both variants were compared with pre-exposure. In WT pre- vs post
      exposure, 36 proteins were differentially expressed. Of the up-regulated
      proteins, translocator protein, Eno, nucleoside diphosphate kinase (Ndk),
      ferritin Dps-family DNA binding protein and peptidyl-prolyl cis-trans isomerase B
      were implicated in invasion and virulence. In SCV pre- vs post-exposure, 27
      proteins were differentially expressed. Among the up-regulated proteins,
      flagellin, Eno, CbbA, Ndk and phenylacetate-coenzyme A ligase have similarly been
      implicated in adhesion, invasion. Protein profiles differences post-exposure
      provide insights into association between morphotypic and phenotypic
      characteristics of colony variants, strengthening the role of B. pseudomallei
      morphotypes in pathogenesis of melioidosis. 

PMID- 25996930
TI  - Deconstructing the polymerase chain reaction: understanding and correcting bias
      associated with primer degeneracies and primer-template mismatches.
AB  - The polymerase chain reaction (PCR) is sensitive to mismatches between primer and
      template, and mismatches can lead to inefficient amplification of targeted
      regions of DNA template. In PCRs in which a degenerate primer pool is employed,
      each primer can behave differently. Therefore, inefficiencies due to different
      primer melting temperatures within a degenerate primer pool, in addition to
      mismatches between primer binding sites and primers, can lead to a distortion of
      the true relative abundance of targets in the original DNA pool. A theoretical
      analysis indicated that a combination of primer-template and primer-amplicon
      interactions during PCR cycles 3-12 is potentially responsible for this
      distortion. To test this hypothesis, we developed a novel amplification strategy,
      entitled "Polymerase-exonuclease (PEX) PCR", in which primer-template
      interactions and primer-amplicon interactions are separated. The PEX PCR method
      substantially and significantly improved the evenness of recovery of sequences
      from a mock community of known composition, and allowed for amplification of
      templates with introduced mismatches near the 3' end of the primer annealing
      sites. When the PEX PCR method was applied to genomic DNA extracted from complex
      environmental samples, a significant shift in the observed microbial community
      was detected. Furthermore, the PEX PCR method provides a mechanism to identify
      which primers in a primer pool are annealing to target gDNA. Primer utilization
      patterns revealed that at high annealing temperatures in the PEX PCR method,
      perfect match annealing predominates, while at lower annealing temperatures,
      primers with up to four mismatches with templates can contribute substantially to
      amplification. The PEX PCR method is simple to perform, is limited to PCR mixes
      and a single exonuclease step which can be performed without reaction cleanup,
      and is recommended for reactions in which degenerate primer pools are used or
      when mismatches between primers and template are possible. 

PMID- 25996931
TI  - Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid
      Metabolism in Drosophila.
AB  - LKB1 plays important roles in governing energy homeostasis by regulating AMP
      activated protein kinase (AMPK) and other AMPK-related kinases, including the
      salt-inducible kinases (SIKs). However, the roles and regulation of LKB1 in lipid
      metabolism are poorly understood. Here we show that Drosophila LKB1 mutants
      display decreased lipid storage and increased gene expression of brummer, the
      Drosophila homolog of adipose triglyceride lipase (ATGL). These phenotypes are
      consistent with those of SIK3 mutants and are rescued by expression of
      constitutively active SIK3 in the fat body, suggesting that SIK3 is a key
      downstream kinase of LKB1. Using genetic and biochemical analyses, we identify
      HDAC4, a class IIa histone deacetylase, as a lipolytic target of the LKB1-SIK3
      pathway. Interestingly, we found that the LKB1-SIK3-HDAC4 signaling axis is
      modulated by dietary conditions. In short-term fasting, the adipokinetic hormone
      (AKH) pathway, related to the mammalian glucagon pathway, inhibits the kinase
      activity of LKB1 as shown by decreased SIK3 Thr196 phosphorylation, and
      consequently induces HDAC4 nuclear localization and brummer gene expression.
      However, under prolonged fasting conditions, AKH-independent signaling decreases
      the activity of the LKB1-SIK3 pathway to induce lipolytic responses. We also
      identify that the Drosophila insulin-like peptides (DILPs) pathway, related to
      mammalian insulin pathway, regulates SIK3 activity in feeding conditions
      independently of increasing LKB1 kinase activity. Overall, these data suggest
      that fasting stimuli specifically control the kinase activity of LKB1 and
      establish the LKB1-SIK3 pathway as a converging point between feeding and fasting
      signals to control lipid homeostasis in Drosophila. 

PMID- 25996932
TI  - Hypothermia and rewarming induce gene expression and multiplication of cells in
      healthy rat prostate tissue.
AB  - Prostate cancer has been extensively studied, but cellular stress responses in
      healthy prostate tissue are rarely investigated. Hypothermia is known to cause
      alterations in mRNA and protein expressions and stability. The aim of this study
      was to use normal rat prostate as a model in order to find out consequences of
      cold exposure and rewarming on the expressions of genes which are either members
      or functionally/structurally related to erythroblastic leukemia viral oncogene B
      (ErbB) signaling pathway. Relative mRNA expressions of amphiregulin (AMR), cyclin
      D1 (CyD1), cyclin-dependent kinase inhibitor 1A (p21), transmembrane form of the
      prostatic acid phosphatase (PAcP), thrombomodulin (TM) and heat shock
      transcription factor 1 (HSF1) in rat ventral prostate were quantified in mild (2
      or 4.5 h at room temperature) and severe (2 or 4.5 h at +10 degrees C)
      hypothermia and in rewarming after cold exposure (2 h at +10 degrees C followed
      by 2 h at room temperature or 3 h at +28 degrees C). AMR protein level, apoptotic
      Bcl-2 associated X protein to B-cell CLL/lymphoma 2 (Bax/Bcl-2) mRNA ratio and
      proliferative index Ki-67 were determined. 4.5-h mild hypothermia, 2-h severe
      hypothermia and rewarming increased expression of all these genes. Elevated
      proliferation index Ki-67 could be seen in 2-h severe hypothermia, and the
      proliferation index had its highest value in longer rewarming with totally
      recovered normal body temperature. Pro-apoptotic tendency could be seen in 2-h
      mild hypothermia while anti-apoptosis was predominant in 4.5-h mild hypothermia
      and in shorter rewarming with only partly recovered body temperature. Hypothermia
      and following rewarming promote the proliferation of cells in healthy rat
      prostate tissue possibly via ErbB signaling pathway. 

PMID- 25996933
TI  - Female gender is a social determinant of diabetes in the Caribbean: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Diabetes (DM) is estimated to affect 10-15% of the adult population
      in the Caribbean. Preventive efforts require population wide measures to address
      its social determinants. We undertook a systematic review to determine current
      knowledge about the social distribution of diabetes, its risk factors and major
      complications in the Caribbean. This paper describes our findings on the
      distribution by gender. METHODS: We searched Medline, Embase and five databases
      through the Virtual Health Library, for Caribbean studies published between 2007
      and 2013 that described the distribution by gender for: known risk factors for
      Type 2 DM, prevalence of DM, and DM control or complications. PRISMA guidance on
      reporting systematic reviews on health equity was followed. Only quantitative
      studies (n>50) were included; each was assessed for risk of bias. Meta-analyses
      were performed, where appropriate, on studies with a low or medium risk of bias,
      using random effects models. RESULTS: We found 50 articles from 27 studies,
      yielding 118 relationships between gender and the outcomes. Women were more
      likely to have DM, obesity, be less physically active but less likely to smoke.
      In meta-analyses of good quality population-based studies odds ratios for women
      vs. men for DM, obesity and smoking were: 1.65 (95% CI 1.43, 1.91), 3.10 (2.43,
      3.94), and 0.24 (0.17, 0.34). Three studies found men more likely to have better
      glycaemic control but only one achieved statistical significance. CONCLUSION AND
      IMPLICATIONS: Female gender is a determinant of DM prevalence in the Caribbean.
      In the vast majority of world regions women are at a similar or lower risk of
      type 2 diabetes than men, even when obesity is higher in women. Caribbean female
      excess of diabetes may be due to a much greater excess of risk factors in women,
      especially obesity. These findings have major implications for preventive
      policies and research.

PMID- 25996934
TI  - The Complex Interaction between Home Environment, Socioeconomic Status, Maternal
      IQ and Early Child Neurocognitive Development: A Multivariate Analysis of Data
      Collected in a Newborn Cohort Study.
AB  - BACKGROUND: The relative role of socioeconomic status (SES), home environment and
      maternal intelligence, as factors affecting child cognitive development in early
      childhood is still unclear. The aim of this study is to analyze the association
      of SES, home environment and maternal IQ with child neurodevelopment at 18
      months. METHODS: The data were collected prospectively in the PHIME study, a
      newborn cohort study carried out in Italy between 2007 and 2010. Maternal
      nonverbal abilities (IQ) were evaluated using the Standard Progressive Matrices,
      a version of the Raven's Progressive Matrices; a direct evaluation of the home
      environment was carried out with the AIRE instrument, designed using the HOME
      (Home Observation for Measurement of the Environment) model; the socioeconomic
      characteristics were evaluated using the SES index which takes into account
      parents occupation, type of employment, educational level, homeownership. The
      study outcome was child neurodevelopment evaluated at 18 months, with the Bayley
      Scales of Infant and Toddler Development Third Edition (BSID III). Linear
      regression analyses and mediation analyses were carried out to evaluate the
      association between the three exposures, and the scaled scores of the three main
      scales of BSID III (cognitive, language and motor scale), with adjustment for a
      wide range of potential explanatory variables. RESULTS: Data from 502 mother
      child pairs were analyzed. Mediation analysis showed a relationship between SES
      and maternal IQ, with a complete mediation effect of home environment in
      affecting cognitive and language domains. A direct significant effect of maternal
      IQ on the BSID III motor development scale and the mediation effect of home
      environment were found. CONCLUSIONS: Our results show that home environment was
      the variable with greater influence on neurodevelopment at 18 months. The
      observation of how parents and children interact in the home context is crucial
      to adequately evaluate early child development.

PMID- 25996935
TI  - Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle;
      Tissue-Specific Distribution and Local Cytokine Expression.
AB  - Tissues obtained post-mortem from cattle persistently infected with foot-and
      mouth disease virus (FMDV) were analyzed to characterize the tissue-specific
      localization of FMDV and partial transcriptome profiles for selected
      immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers
      infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall
      viral detection in the dorsal nasopharynx (80.95%) and dorsal soft palate
      (71.43%). FMDV was less frequently detected in laryngeal mucosal tissues,
      oropharyngeal mucosal sites, and lymph nodes draining the pharynx.
      Immunomicroscopy indicated that within persistently infected mucosal tissues,
      FMDV antigens were rarely detectable within few epithelial cells in regions of
      mucosa-associated lymphoid tissue (MALT). Transcriptome analysis of persistently
      infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general
      trend of decreased mRNA levels compared to uninfected control animals. Although,
      statistically significant differences were not observed, greatest suppression of
      relative expression (RE) was identified for IP-10 (RE = 0.198), IFN-beta (RE =
      0.269), IL-12 (RE = 0.275), and IL-2 (RE = 0.312). Increased relative expression
      was detected for IL-6 (RE = 2.065). Overall, this data demonstrates that during
      the FMDV carrier state in cattle, viral persistence is associated with epithelial
      cells of the nasopharynx in the upper respiratory tract and decreased levels of
      mRNA for several immunoregulatory cytokines in the infected tissues. 

PMID- 25996936
TI  - Context-Dependent Role of Mitochondrial Fusion-Fission in Clonal Expansion of
      mtDNA Mutations.
AB  - The accumulation of mutant mitochondrial DNA (mtDNA) molecules in aged cells has
      been associated with mitochondrial dysfunction, age-related diseases and the
      ageing process itself. This accumulation has been shown to often occur clonally,
      where mutant mtDNA grow in number and overpopulate the wild-type mtDNA. However,
      the cell possesses quality control (QC) mechanisms that maintain mitochondrial
      function, in which dysfunctional mitochondria are isolated and removed by
      selective fusion and mitochondrial autophagy (mitophagy), respectively. The aim
      of this study is to elucidate the circumstances related to mitochondrial QC that
      allow the expansion of mutant mtDNA molecules. For the purpose of the study, we
      have developed a mathematical model of mitochondrial QC process by extending our
      previous validated model of mitochondrial turnover and fusion-fission. A global
      sensitivity analysis of the model suggested that the selectivity of mitophagy and
      fusion is the most critical QC parameter for clearing de novo mutant mtDNA
      molecules. We further simulated several scenarios involving perturbations of key
      QC parameters to gain a better understanding of their dynamic and synergistic
      interactions. Our model simulations showed that a higher frequency of
      mitochondrial fusion-fission can provide a faster clearance of mutant mtDNA, but
      only when mutant-rich mitochondria that are transiently created are efficiently
      prevented from re-fusing with other mitochondria and selectively removed.
      Otherwise, faster fusion-fission quickens the accumulation of mutant mtDNA.
      Finally, we used the insights gained from model simulations and analysis to
      propose a possible circumstance involving deterioration of mitochondrial QC that
      permits mutant mtDNA to expand with age. 

PMID- 25996937
TI  - Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation
      Reflecting Use-Dependent Plasticity.
AB  - Previous research suggests that anodal transcranial direct current stimulation
      (tDCS) over the primary motor cortex (M1) modulates NMDA receptor dependent
      processes that mediate synaptic plasticity. Here we test this proposal by
      applying anodal versus sham tDCS while subjects practiced to flex the thumb as
      fast as possible (ballistic movements). Repetitive practice of this task has been
      shown to result in performance improvements that reflect use-dependent plasticity
      resulting from NMDA receptor mediated, long-term potentiation (LTP)-like
      processes. Using a double-blind within-subject cross-over design, subjects (n=14)
      participated either in an anodal or a sham tDCS session which were at least 3
      months apart. Sham or anodal tDCS (1 mA) was applied for 20 min during motor
      practice and retention was tested 30 min, 24 hours and one week later. All
      subjects improved performance during each of the two sessions (p < 0.001) and
      learning gains were similar. Our main result is that long term retention
      performance (i.e. 1 week after practice) was significantly better when practice
      was performed with anodal tDCS than with sham tDCS (p < 0.001). This effect was
      large (Cohen's d=1.01) and all but one subject followed the group trend. Our data
      strongly suggest that anodal tDCS facilitates long-term memory formation
      reflecting use-dependent plasticity. Our results support the notion that anodal
      tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is
      in accordance with previous research. 

PMID- 25996938
TI  - Association of serum level of growth differentiation factor 15 with liver
      cirrhosis and hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high
      mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard
      serum marker for the detection of HCC, but its sensitivity and specificity are
      unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We
      previously reported that growth differentiation factor 15 (GDF15) was
      significantly induced in HCV-infected hepatocytes. This study aimed to
      investigate GDF15 expression and its correlation with hepatitis virus-related
      liver diseases. A total of 412 patients with various liver diseases were studied.
      Healthy and Mycobacterium tuberculosis-infected subjects were included as
      controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were
      significantly increased in patients with HCC (6.66+/-0.67 ng/mL, p<0.0001) and
      cirrhosis (6.51+/-1.47 ng/mL, p<0.0001) compared with healthy controls (0.31+/
      0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately
      elevated (1.34+/-0.19 ng/mL and 2.13+/-0.53 ng/mL, respectively). Compared with
      HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6%
      at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or
      HCC. In HCC patients, the area under the receiver operating curve was 0.84 for
      GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15
      levels did not significantly differ between the high-AFP and low-AFP groups.
      GDF15 protein expression in HCC was significantly higher than that in the
      corresponding adjacent paracarcinomatous tissue and normal liver. Using a
      combination of GDF15 and AFP will improve the sensitivity and specificity of HCC
      diagnosis. Further research and the clinical implementation of serum GDF15
      measurement as a biomarker for HCC and cirrhosis are recommended. 

PMID- 25996939
TI  - Right ventricular sex differences in patients with idiopathic pulmonary arterial
      hypertension characterised by magnetic resonance imaging: pair-matched case
      controlled study.
AB  - PURPOSE: Sex differences exist in both the prevalence and survival of patients
      with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently
      affected by the condition but have worse outcome as compared to females. We
      sought to characterise the sex related differences in right ventricular
      remodelling in age matched male and female patients with IPAH using cardiac
      magnetic resonance imaging (MRI). METHODS: A case controlled pair-matched study
      was conducted with patients matched by age and sex. Steady state free precession
      (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass
      measurements were corrected for age, sex and BSA according to reference data.
      RESULTS: 40 age and sex matched patients with IPAH were identified. The mean age
      was 57 (SD 17) in both male and female cohorts. Men had proportionally lower
      right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume
      than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no
      significant difference in RV mass or haemodynamic indices of mPAP and PVR between
      males and females. CONCLUSION: Male patients with IPAH have proportionally worse
      RV function despite similar afterload. We hypothesise that adaptive remodelling
      of the RV in response to increased afterload in IPAH is more effective in
      females.

PMID- 25996940
TI  - Snakebites and scorpion stings in the Brazilian Amazon: identifying research
      priorities for a largely neglected problem.

PMID- 25996941
TI  - CleavPredict: A Platform for Reasoning about Matrix Metalloproteinases
      Proteolytic Events.
AB  - CleavPredict (http://cleavpredict.sanfordburnham.org) is a Web server for
      substrate cleavage prediction for matrix metalloproteinases (MMPs). It is
      intended as a computational platform aiding the scientific community in reasoning
      about proteolytic events. CleavPredict offers in silico prediction of cleavage
      sites specific for 11 human MMPs. The prediction method employs the MMP specific
      position weight matrices (PWMs) derived from statistical analysis of high
      throughput phage display experimental results. To augment the substrate cleavage
      prediction process, CleavPredict provides information about the structural
      features of potential cleavage sites that influence proteolysis. These include:
      secondary structure, disordered regions, transmembrane domains, and solvent
      accessibility. The server also provides information about subcellular location,
      co-localization, and co-expression of proteinase and potential substrates, along
      with experimentally determined positions of single nucleotide polymorphism (SNP),
      and posttranslational modification (PTM) sites in substrates. All this
      information will provide the user with perspectives in reasoning about
      proteolytic events. CleavPredict is freely accessible, and there is no login
      required. 

PMID- 25996942
TI  - Development of apical blebbing in the boar epididymis.
AB  - Microvesicles are of increasing interest in biology as part of normal function of
      numerous systems; from the immune system (T cell activation) to implantation of
      the embryo (invasion of the trophoblasts) and sperm maturation (protein transfer
      in the epididymis). Yet, the mechanisms involved in the appearance of apical
      blebbing from healthy cells as part of their normal function remain understudied.
      Microvesicles are produced via one of two pathways: exocytosis or apical blebbing
      also termed ectocytosis. This work quantifies the histological appearance of
      apical blebbing in the porcine epididymis during development and examines the
      role of endogenous estrogens in regulating this blebbing. Apical blebbing appears
      at puberty and increases in a linear manner into sexual maturity suggesting that
      this blebbing is a mature phenotype. Endogenous estrogen levels were reduced with
      an aromatase inhibitor but such a reduction did not affect apical blebbing in
      treated animals compared with their vehicle-treated littermates. Epididymal
      production of apical blebs is a secretion mechanism of functionally mature
      principal cells regulated by factors other than estradiol. 

PMID- 25996943
TI  - Controlling Factors of Soil CO2 Efflux in Pinus yunnanensis across Different
      Stand Ages.
AB  - The characteristics of soil respiration (Rs) across different stand ages have not
      been well investigated. In this study, we identified temporal variation of Rs and
      its driving factors under three nature forest stands (e.g. 15-yr-old, 30-yr-old,
      and 45-yr-old) of Pinus yunnanensis in the Plateau of Mid-Yunnan, China. No
      consistent tendency was found on the change of Rs with the stand ages. Rs was
      ranked in the order of 30-yr-old > 45-yr-old >15-yr-old. Rs in 15-yr-old stand
      was the most sensitive to soil temperature (Ts) among the three sites. However,
      Ts only explained 30-40% of the seasonal dynamics of Rs at the site. Soil water
      content (Sw) was the major controlling factor of temporal variation at the three
      sites. Sw explained 88-93% of seasonal variations of Rs in the 30-yr-old stand,
      and 63.7-72.7% in the 15-yr-old and 79.1-79.6% in the 45-yr-old stands. In
      addition, we found that pH, available nitrogen (AN), C/N and total phosphorus
      (TP) contributed significantly to the seasonal variation of Rs. Sw was
      significantly related with pH, total nitrogen (TN), AN and TP, suggesting that Sw
      can affect Rs through improving soil acid-base property and soil texture, and
      increasing availability of soil nutrient. The results indicated that besides soil
      water, soil properties (e. g. pH, AN, C/N and TP) were also the important in
      controlling the temporal variations of Rs across different stand ages in the
      nature forestry. 

PMID- 25996945
TI  - Study on the coordination structure of pt sorbed on bacterial cells using x-ray
      absorption fine structure spectroscopy.
AB  - Biosorption has been intensively investigated as a promising technology for the
      recovery of precious metals from solution. However, the detailed mechanism
      responsible for the biosorption of Pt on a biomass is not fully understood
      because of a lack of spectroscopic studies. We applied X-ray absorption fine
      structure spectroscopy to elucidate the coordination structure of Pt sorbed on
      bacterial cells. We examined the sorption of Pt(II) and Pt(IV) species on
      bacterial cells of Bacillus subtilis and Shewanella putrefaciens in NaCl
      solutions. X-ray absorption near-edge structure and extended X-ray absorption
      fine structure (EXAFS) of Pt-sorbed bacteria suggested that Pt(IV) was reduced to
      Pt(II) on the cell's surface, even in the absence of an organic material as an
      exogenous electron donor. EXAFS spectra demonstrated that Pt sorbed on bacterial
      cells has a fourfold coordination of chlorine ions, similar to PtCl42-, which
      indicated that sorption on the protonated amine groups of the bacterial cells.
      This work clearly demonstrated the coordination structure of Pt sorbed on
      bacterial cells. The findings of this study will contribute to the understanding
      of Pt biosorption on biomass, and facilitate the development of recovery methods
      for rare metals using biosorbent materials. 

PMID- 25996944
TI  - The Mitochondrial Genomes of the Nudibranch Mollusks, Melibe leonina and Tritonia
      diomedea, and Their Impact on Gastropod Phylogeny.
AB  - The phylogenetic relationships among certain groups of gastropods have remained
      unresolved in recent studies, especially in the diverse subclass Opisthobranchia,
      where nudibranchs have been poorly represented. Here we present the complete
      mitochondrial genomes of Melibe leonina and Tritonia diomedea (more recently
      named T. tetraquetra), two nudibranchs from the unrepresented Cladobranchia
      group, and report on the resulting phylogenetic analyses. Both genomes coded for
      the typical thirteen protein-coding genes, twenty-two transfer RNAs, and two
      ribosomal RNAs seen in other species. The twelve-nucleotide deletion previously
      reported for the cytochrome oxidase 1 gene in several other Melibe species was
      further clarified as three separate deletion events. These deletions were not
      present in any opisthobranchs examined in our study, including the newly
      sequenced M. leonina or T. diomedea, suggesting that these previously reported
      deletions may represent more recently divergent taxa. Analysis of the secondary
      structures for all twenty-two tRNAs of both M. leonina and T. diomedea indicated
      truncated d arms for the two serine tRNAs, as seen in some other heterobranchs.
      In addition, the serine 1 tRNA in T. diomedea contained an anticodon not yet
      reported in any other gastropod. For phylogenetic analysis, we used the thirteen
      protein-coding genes from the mitochondrial genomes of M. leonina, T. diomedea,
      and seventy-one other gastropods. Phylogenetic analyses were performed for both
      the class Gastropoda and the subclass Opisthobranchia. Both Bayesian and maximum
      likelihood analyses resulted in similar tree topologies. In the Opisthobranchia,
      the five orders represented in our study were monophyletic (Anaspidea,
      Cephalaspidea, Notaspidea, Nudibranchia, Sacoglossa). In Gastropoda, two of the
      three traditional subclasses, Opisthobranchia and Pulmonata, were not
      monophyletic. In contrast, four of the more recently named gastropod clades
      (Vetigastropoda, Neritimorpha, Caenogastropoda, and Heterobranchia) were all
      monophyletic, and thus appear to be better classifications for this diverse
      group. 

PMID- 25996946
TI  - The Contributions of Onchocerciasis Control and Elimination Programs toward the
      Achievement of the Millennium Development Goals.
AB  - In 2000, 189 member states of the United Nations (UN) developed a plan for peace
      and development, which resulted in eight actionable goals known as the Millennium
      Development Goals (MDGs). Since their inception, the MDGs have been considered
      the international standard for measuring development progress and have provided a
      blueprint for global health policy and programming. However, emphasis upon the
      achievement of priority benchmarks around the "big three" diseases--namely HIV,
      tuberculosis (TB), and malaria--has influenced global health entities to
      disproportionately allocate resources. Meanwhile, several tropical diseases that
      almost exclusively impact the poorest of the poor continue to be neglected,
      despite the existence of cost-effective and feasible methods of control or
      elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more
      commonly known as river blindness, is a debilitating and stigmatizing disease
      primarily affecting individuals living in remote and impoverished areas.
      Onchocerciasis control is considered to be one of the most successful and cost
      effective public health campaigns ever launched. In addition to improving the
      health and well-being of millions of individuals, these programs also lead to
      improvements in education, agricultural production, and economic development in
      affected communities. Perhaps most pertinent to the global health community,
      though, is the demonstrated effectiveness of facilitating community engagement by
      allowing communities considerable ownership with regard to drug delivery. This
      paper reviews the contributions that such concentrated efforts to control and
      eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw
      the attention of public policymakers and global health funders to the importance
      of the struggle against onchocerciasis as a model for community-directed
      interventions to advance health and development, and to advocate for NTDs
      inclusion in the post 2015 agenda.

PMID- 25996947
TI  - Guidelines for Audiologists on the Benefits and Limitations of Genetic Testing.
AB  - PURPOSE: This tutorial provides information to aid audiologists in determining
      when a referral for a genetics evaluation is appropriate for a patient with
      hearing loss. Direction is given on discussing the benefits and limitations of
      genetic testing with parents of children with hearing loss. METHOD: Genetic
      patterns of inheritance are reviewed, particularly in reference to syndromic and
      nonsyndromic forms of hearing loss. A review of pertinent literature was
      performed. CONCLUSION: Audiologists are in a unique position to facilitate
      investigation into the etiology of a patient's hearing loss. This is of high
      importance in genetic etiologies because the diagnosis can provide information on
      recurrence risks and other potential health implications. Suggestions are made to
      help audiologists recognize when a genetics referral is warranted, counsel
      patients and their parents about the benefits and limitations of genetic testing,
      and interpret genetic test results.

PMID- 25996948
TI  - Lung density changes with growth and inflation.
AB  - BACKGROUND: With body growth from childhood, the lungs can enlarge by either
      increasing the volume of air in the periphery (as would occur with inspiration)
      or by increasing the number of peripheral acinar units. In the former case, the
      lung tissue density would decrease with inflation, whereas in the latter case,
      the lung density would be relatively constant as the lung grows. To address this
      fundamental structural issue, we measured the CT scan density in human subjects
      of widely varying size at two different lung volumes. METHODS: Five hundred one
      subjects were enrolled in the study. They underwent a chest CT scan at full
      inspiration and another scan at end expiration. Spirometry, body plethysmography,
      and diffusing capacity of the lung for carbon monoxide were also measured.
      RESULTS: There was a strong correlation between the size of the lungs measured at
      full inspiration on CT scan and the mean lung density (r = -0.72, P = .001).
      People with larger lungs had significantly lower mean lung density. These density
      changes among different subjects overlapped the density changes within subjects
      at different lung volumes. CONCLUSIONS: Lung structure in subjects with larger
      lungs is different from that in subjects with smaller lungs. Tissue volume does
      not increase in proportion to lung size, as would be required if larger lungs
      just had more alveoli. These observations suggest that the growth of the lung
      into adulthood is not accompanied by new alveoli, but rather by enlargement of
      existing structures. The presence of greater air spaces in larger lungs could
      impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD.

PMID- 25996950
TI  - Correction: early parental loss and self-rated health of older women and men: a
      population-based, multi-country study.

PMID- 25996951
TI  - Structure and Ultrastructure of the Endodermal Region of the Alimentary Tract in
      the Freshwater Shrimp Neocaridina heteropoda (Crustacea, Malacostraca).
AB  - The freshwater shrimp Neocaridina heteropoda (Crustacea, Malacostraca, Decapoda)
      originates from Asia and is one of the species that is widely available all over
      the world because it is the most popular shrimp that is bred in aquaria. The
      structure and the ultrastructure of the midgut have been described using X-ray
      microtomography, transmission electron microscopy, light and fluorescence
      microscopes. The endodermal region of the alimentary system in N. heteropoda
      consists of an intestine and a hepatopancreas. No differences were observed in
      the structure and ultrastructure of males and females of the shrimp that were
      examined. The intestine is a tube-shaped organ and the hepatopancreas is composed
      of two large diverticles that are divided into the blind-end tubules.
      Hepatopancreatic tubules have three distinct zones - proximal, medial and distal.
      Among the epithelial cells of the intestine, two types of cells were
      distinguished - D and E-cells, while three types of cells were observed in the
      epithelium of the hepatopancreas - F, B and E-cells. Our studies showed that the
      regionalization in the activity of cells occurs along the length of the
      hepatopancreatic tubules. The role and ultrastructure of all types of epithelial
      cells are discussed, with the special emphasis on the function of the E-cells,
      which are the midgut regenerative cells. Additionally, we present the first
      report on the existence of an intercellular junction that is connected with the E
      cells of Crustacea. 

PMID- 25996949
TI  - TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1
      Mediated Growth and Survival Pathway Activation.
AB  - The Epstein-Barr virus (EBV) encoded oncoprotein Latent Membrane Protein 1 (LMP1)
      signals through two C-terminal tail domains to drive cell growth, survival and
      transformation. The LMP1 membrane-proximal TES1/CTAR1 domain recruits TRAFs to
      activate MAP kinase, non-canonical and canonical NF-kB pathways, and is critical
      for EBV-mediated B-cell transformation. TRAF1 is amongst the most highly TES1
      induced target genes and is abundantly expressed in EBV-associated
      lymphoproliferative disorders. We found that TRAF1 expression enhanced LMP1 TES1
      domain-mediated activation of the p38, JNK, ERK and canonical NF-kB pathways, but
      not non-canonical NF-kB pathway activity. To gain insights into how TRAF1
      amplifies LMP1 TES1 MAP kinase and canonical NF-kB pathways, we performed
      proteomic analysis of TRAF1 complexes immuno-purified from cells uninduced or
      induced for LMP1 TES1 signaling. Unexpectedly, we found that LMP1 TES1 domain
      signaling induced an association between TRAF1 and the linear ubiquitin chain
      assembly complex (LUBAC), and stimulated linear (M1)-linked polyubiquitin chain
      attachment to TRAF1 complexes. LMP1 or TRAF1 complexes isolated from EBV
      transformed lymphoblastoid B cell lines (LCLs) were highly modified by M1-linked
      polyubiqutin chains. The M1-ubiquitin binding proteins IKK-gamma/NEMO, A20 and
      ABIN1 each associate with TRAF1 in cells that express LMP1. TRAF2, but not the
      cIAP1 or cIAP2 ubiquitin ligases, plays a key role in LUBAC recruitment and M1
      chain attachment to TRAF1 complexes, implicating the TRAF1:TRAF2 heterotrimer in
      LMP1 TES1-dependent LUBAC activation. Depletion of either TRAF1, or the LUBAC
      ubiquitin E3 ligase subunit HOIP, markedly impaired LCL growth. Likewise, LMP1 or
      TRAF1 complexes purified from LCLs were decorated by lysine 63 (K63)-linked
      polyubiqutin chains. LMP1 TES1 signaling induced K63-polyubiquitin chain
      attachment to TRAF1 complexes, and TRAF2 was identified as K63-Ub chain target.
      Co-localization of M1- and K63-linked polyubiquitin chains on LMP1 complexes may
      facilitate downstream canonical NF-kB pathway activation. Our results highlight
      LUBAC as a novel potential therapeutic target in EBV-associated
      lymphoproliferative disorders. 

PMID- 25996953
TI  - Interferon in polycythemia vera and related neoplasms. Can it become the
      treatment of choice without a randomized trial?
AB  - Recently, it was concluded that the optimal therapy for essential thrombocythemia
      and polycythemia vera, either recombinant interferon alpha (rIFNalpha) or
      hydroxyurea can only be determined by the completion of a randomized clinical
      trial. We present our recommendations for the use of rIFNalpha for those patients
      who are not candidates for the randomized trial. We argue for rethinking the
      approach whether we should continue to wait for the results from a randomized
      trial before recommending treatment with rIFNalpha for those unable and unwilling
      to enter these trials. The interferon story shows that clinical experience may be
      an alternative path to follow when making treatment decisions and recommendations
      in orphan diseases. 

PMID- 25996952
TI  - Identification of the Adapter Molecule MTSS1 as a Potential Oncogene-Specific
      Tumor Suppressor in Acute Myeloid Leukemia.
AB  - The adapter protein metastasis suppressor 1 (MTSS1) is implicated as a tumor
      suppressor or tumor promoter, depending on the type of solid cancer. Here, we
      identified Mtss1 expression to be increased in AML subsets with favorable
      outcome, while suppressed in high risk AML patients. High expression of MTSS1
      predicted better clinical outcome of patients with normal-karyotype AML.
      Mechanistically, MTSS1 expression was negatively regulated by FLT3-ITD signaling
      but enhanced by the AML1-ETO fusion protein. DNMT3B, a negative regulator of
      MTSS1, showed strong binding to the MTSS1 promoter in PML-RARA positive but not
      AML1-ETO positive cells, suggesting that AML1-ETO leads to derepression of MTSS1.
      Pharmacological treatment of AML cell lines carrying the FLT3-ITD mutation with
      the specific FLT3 inhibitor PKC-412 caused upregulation of MTSS1. Moreover,
      treatment of acute promyelocytic cells (APL) with all-trans retinoic acid (ATRA)
      increased MTSS1 mRNA levels. Taken together, our findings suggest that MTSS1
      might have a context-dependent function and could act as a tumor suppressor,
      which is pharmacologically targetable in AML patients. 

PMID- 25996955
TI  - The complete mitochondrial genome of the Terapon jarbua (Perciformes:
      Terapontidae).
AB  - In the present study, the complete mitochondrial genome of the Terapon jarbua has
      been sequenced. The mitochondrial genome is 16,570 bp in length, containing 13
      protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one
      control region. The gene order and the composition of T. jarbua mitochondrial
      genome were similar to that of most other vertebrates. The overall nucleotides
      base composition of the heavy strand is A (27.36%), G (16.57%), C (29.87%), and T
      (26.20%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight
      tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The
      tRNA-Ser2 gene lacked DHC arm and could not fold into a typical clover-leaf
      secondary structure. Seen from the phylogenetic tree, T. jarbua, Bidyanus
      bidyanus, and Rhynchopelates oxyrhynchus from the same family (Terapontidae)
      clustered into one branch and were significantly divergent from the other
      families of closely related fish species.

PMID- 25996954
TI  - A Pectate Lyase-Coding Gene Abundantly Expressed during Early Stages of Infection
      Is Required for Full Virulence in Alternaria brassicicola.
AB  - Alternaria brassicicola causes black spot disease of Brassica species. The
      functional importance of pectin digestion enzymes and unidentified phytotoxins in
      fungal pathogenesis has been suspected but not verified in A. brassicicola. The
      fungal transcription factor AbPf2 is essential for pathogenicity and induces 106
      genes during early pathogenesis, including the pectate lyase-coding gene, PL1332.
      The aim of this study was to test the importance and roles of PL1332 in
      pathogenesis. We generated deletion strains of the PL1332 gene, produced
      heterologous PL1332 proteins, and evaluated their association with virulence.
      Deletion strains of the PL1332 gene were approximately 30% less virulent than
      wild-type A. brassicicola, without showing differences in colony expansion on
      solid media and mycelial growth in nutrient-rich liquid media or minimal media
      with pectins as a major carbon source. Heterologous PL1332 expressed as fusion
      proteins digested polygalacturons in vitro. When the fusion proteins were
      injected into the apoplast between leaf veins of host plants the tissues turned
      dark brown and soft, resembling necrotic leaf tissue. The PL1332 gene was the
      first example identified as a general toxin-coding gene and virulence factor
      among the 106 genes regulated by the transcription factor, AbPf2. It was also the
      first gene to have its functions investigated among the 19 pectate lyase genes
      and several hundred putative cell-wall degrading enzymes in A. brassicicola.
      These results further support the importance of the AbPf2 gene as a key
      pathogenesis regulator and possible target for agrochemical development. 

PMID- 25996956
TI  - First complete mitochondrial genome sequence from the tribelocephaline assassin
      bugs (Hemiptera: Reduviidae).
AB  - The complete mitochondrial genome (mitogenome) of Opistoplatys sp. was
      determined, which was the first representation from the assassin bug subfamily
      Tribelocephalinae. The mitogenome is a typical circular DNA molecule of 15,615 bp
      and contains 37 genes and a putative control region. All the 13 protein-coding
      genes initiate with ATN codons and mostly terminate with TAA or TAG codons except
      for COII, COIII, and ND5 genes use a single T residue as the termination codon.
      All the 22 tRNAs have the clover-leaf structure except for the tRNASer(AGN) with
      the length ranging from 60 to 72 bp. The control region is 1068 bp in length and
      includes 456 bp tandem repeat sequence with four 94-bp tandem repeat units and a
      partial fifth (80 bp). In the sampled subfamilies of Reduviidae, Peiratinae + the
      remaining subfamilies, Triatominae + Stenopodainae, Tribelocephalinae +
      Ectrichodiinae, are recovered in phylogenetic analyses with high supports.

PMID- 25996957
TI  - Capturing the temporal sequence of interaction in young siblings.
AB  - We explored whether young children exhibit subtypes of behavioral sequences
      during sibling interaction. Ten-minute, free-play observations of over 300
      sibling dyads were coded for positivity, negativity and disengagement. The data
      were analyzed using growth mixture modeling (GMM). Younger (18-month-old)
      children's temporal behavioral sequences showed a harmonious (53%) and a casual
      (47%) class. Older (approximately four-year-old) children's behavior was more
      differentiated revealing a harmonious (25%), a deteriorating (31%), a recovery
      (22%) and a casual (22%) class. A more positive maternal affective climate was
      associated with more positive patterns. Siblings' sequential behavioral patterns
      tended to be complementary rather than reciprocal in nature. The study
      illustrates a novel use of GMM and makes a theoretical contribution by showing
      that young children exhibit distinct types of temporal behavioral sequences that
      are related to parenting processes. 

PMID- 25996959
TI  - Development of preparative and analytical methods of the hop bitter acid oxide
      fraction and chemical properties of its components.
AB  - The bitter acids in hops (Humulus lupulus L.) and beer, such as alpha-, beta-,
      and iso-alpha-acids, are known to affect beer quality and display various
      physiological effects. However, these compounds readily oxidize, and the effect
      of the oxides on the properties of beer or their potential health benefits are
      not well understood. In this study, we developed a simple preparative method for
      the bitter acid oxide fraction derived from hops and designated the constituents
      as matured hop bitter acids (MHBA). HPLC-PDA-ESI/HRMS and MS(2) revealed that
      MHBA are primarily composed of alpha-acid-derived oxides, which possess a common
      beta-tricarbonyl moiety in their structures similar to alpha-, beta-, and iso
      alpha-acids. We also developed a quantitative analytical method of whole MHBA by
      HPLC, which showed high precision and reproducibility. Using our newly developed
      method, the concentration of whole MHBA in several commercial beers was
      evaluated. Our results will promote the study of bitter acid oxides. 

PMID- 25996958
TI  - Incident retinal vein occlusions and estimated cerebrospinal fluid pressure. The
      Beijing Eye Study.
AB  - PURPOSE: To examine whether the incidence of retinal vein occlusions (RVOs) is
      associated with estimated cerebrospinal fluid pressure (CSFP). METHODS: The
      population-based Beijing Eye Study, which included 4439 subjects (age: 40 +
      years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of
      the survivors). Fundus photographs were examined for the new development of RVOs,
      differentiated into central RVOs (CRVOs) and branch RVOs (BRVOs). CSFP was
      calculated as CSFP [mmHg] = 0.44 * Body Mass Index [kg/m(2) ] + 0.16 * Diastolic
      Blood Pressure [mmHg]-0.18 * Age[Years]. RESULTS: Incident BRVOs were detected in
      50 eyes and incident CRVOs in 8 eyes. BRVOs were located at arterio-venous
      crossings in 39 eyes. In multivariate analysis, a higher estimated CSFP was
      associated with a higher incidence of CRVOs (p = 0.004; standardized coefficient
      beta: 0.06; regression coefficient B: 5.35; 95% confidence interval (CI):1.73,
      8.96) after adjusting for urban region (p < 0.001; beta: -0.52; B: -3.93; 95% CI:
      -4.29, -3.57), higher educational level (p = 0.001; beta: 0.13; B: 0.44; 95% CI:
      0.28, 0.60), higher blood concentrations of triglycerides (p < 0.001; beta: 0.08;
      B: 0.11; 95% CI: 0.05, 0.16) and higher intraocular pressure (p < 0.001; beta:
      0.16; B:0.21; 95% CI: 0.16, 0.27). As a corollary, a higher incidence of RVOs as
      a whole, as well as a higher incidence of CRVOs combined with a higher incidence
      of BRVOs originating at the optic nerve head, both were significantly associated
      with higher estimated CSFP (p = 0.002; odds ratio (OR): 1.15; 95% CI: 1.05, 1.25;
      and p = 0.037; OR: 1.17; 95% CI: 1.01, 1.35, respectively) after adjusting for
      older age. CONCLUSIONS: A higher estimated CSFP was associated with a higher
      incidence of RVOs originating at the optic nerve head (i.e. CRVOs, hemi-central
      RVOs and BRVOs originating at the optic nerve head), and vice versa, a higher
      incidence of RVOs was associated with a higher estimated CSFP. It suggested an
      influence of higher estimated CSFP on higher central retinal vein pressure.

PMID- 25996961
TI  - Comment on the German draft legislation on hydraulic fracturing: the need for an
      accurate state of knowledge and for independent scientific research.

PMID- 25996960
TI  - The Prevalence and Incidence of Latent Tuberculosis Infection and Its Associated
      Factors among Village Doctors in China.
AB  - BACKGROUND: China is a high tuberculosis (TB) burden country. More than half of
      acute TB cases first seek medical care in village doctors' clinics or community
      health centers. Despite being responsible for patient referral and management,
      village doctors are not systematically evaluated for TB infection or disease. We
      assessed prevalence and incidence of latent TB infection (LTBI) among village
      doctors in China. METHODS AND FINDINGS: A longitudinal study was conducted in
      Inner Mongolia Autonomous Region. We administered a questionnaire on demographics
      and risk factors for TB exposure and disease; Tuberculin skin testing (TST) and
      QuantiFERON-TB Gold in-tube assay (QFT-GIT) was conducted at baseline and
      repeated 12 months later. We used a logistic regression model to calculate
      adjusted odds ratios (ORs) for risk factors for TST and QFT-GIT prevalence and
      incidence. At the time of follow up, 19.5% of the 880 participating village
      doctors had a positive TST and 46.0% had a positive QFT-GIT result. Factors
      associated with TST prevalence included having a BCG scar (OR = 1.45, 95%CI 1.03
      2.04) and smoking (OR = 1.69, 95%CI 1.17-2.44). Risk factors associated with QFT
      GIT prevalence included being male (OR = 2.17, 95%CI 1.63-2.89), below college
      education (OR=1.42, 95%CI 1.01-1.97), and working for >=25 years as a village
      doctor (OR = 1.64, 95%CI 1.12-2.39). The annual incidence of LTBI was 11.4% by
      TST and 19.1% by QFT-GIT. QFT-GIT conversion was associated with spending 15
      minutes or more per patient on average (OR = 2.62, 95%CI 1.39-4.97) and having
      BCG scar (OR = 0.53, 95%CI 0.28-1.00). CONCLUSIONS: Prevalence and incidence of
      LTBI among Chinese village doctors is high. TB infection control measures should
      be strengthened among village doctors and at village healthcare settings.

PMID- 25996962
TI  - Nerve Ultrasound in Peripheral Neuropathies: A Review.
AB  - Peripheral neuropathies are one of the most common reasons for seeking
      neurological care in everyday practice. Electrophysiological studies remain
      fundamental for the diagnosis and etiological classification of peripheral nerve
      impairment. The recent technological development though of high resolution
      ultrasound has allowed the clinician to obtain detailed structural images of
      peripheral nerves. Nerve ultrasound mainly focuses on the evaluation of the cross
      sectional area, cross sectional area variability along the anatomical course,
      echogenity, vascularity and mobility of the peripheral nerves. An increase of the
      cross sectional area, hypervascularity, disturbed fascicular echostructure and
      reduced nerve mobility are some of the most common findings of entrapments
      neuropathies, such as the carpal or cubital tunnel syndrome. Both the cross
      sectional area increase and the hypervascularity detected with the Doppler
      technique seem to correlate significantly with the clinical and
      electrophysiological severity of the later mononeuropathies. Significantly
      greater cross sectional area values of the clinically affected cervical nerve
      root are often detected in cases of cervical radiculopathy. In such cases, the
      ultrasound findings seem also to correlate significantly with disease duration.
      On the other hand, multifocal cross sectional area enlargement of cervical roots
      and/or peripheral nerves is often documented in cases of immune-mediated
      neuropathies. None of the later pathological ultrasound findings seem to
      correlate significantly with the electrophysiological parameters or the
      functional disability. The aim of this review is to provide a timely update on
      the role of neuromuscular ultrasound in the diagnostic of the most common
      entrapment and immune-mediated peripheral neuropathies in clinical practice.

PMID- 25996963
TI  - The role of diabetes in acromegaly associated neoplasia.
AB  - BACKGROUND: The risk and mortality due to cancer in patients with acromegaly have
      been previously investigated. Although GH/IGF-1 excess provides a probable
      pathophysiological explanation, the degree of IGF-1 excess and the role in
      acromegaly-associated neoplasms of diabetes, a common comorbidity in acromegaly
      with known association with cancer, remains unclear. METHODS: Acromegalic
      patients treated in three Canadian referral centers (Toronto, Montreal, Edmonton)
      were included. All available clinical information was recorded including: age,
      initial and last percentage of the upper limit of normal (%ULN) IGF-1 levels,
      comorbidities and other neoplasms (benign and malignant). RESULTS: 408 cases were
      assessed. 185 were women (45.3%), 126 (30.9%) developed extra-pituitary
      neoplasms: 55 malignant and 71 benign. The most frequent anatomic site was the
      gastrointestinal tract (46 [11.3%]), followed by head and neck (36 [8.8%]) and
      multiple locations (14 [3.4%]). 106 (26.0%) cases had diabetes. Initial IGF-1 was
      significantly higher in men older than 50 (380.15 vs. 284.78, p = 0.001) when
      compared to men younger than 50. Diabetics showed significantly higher initial
      IGF-1 (389.38 vs. 285.27, p = 0.009), as did diabetics older than 50 compared
      with those without diabetes. 45.3% (48/106) of cases with diabetes developed
      extra-pituitary neoplasms vs. 24.3% (71/292) without diabetes (p = 0.001, OR:
      2.576 95%CI 1.615-4.108). 22.6% (24/106) of cases with diabetes developed
      malignant tumors vs. 9.2% (27/292), (p < 0.001, OR 2.873, 95%CI 1.572-5.250).
      CONCLUSIONS: These data suggest that acromegalic patients with diabetes are more
      likely to develop extra-pituitary neoplasms and their initial IGF-1 levels are
      higher. The contribution of IGF-1 vs. diabetes alone or in combination in the
      development of extra-pituitary neoplasms warrants further investigation.

PMID- 25996964
TI  - A simple method for measuring power, force, velocity properties, and mechanical
      effectiveness in sprint running.
AB  - This study aimed to validate a simple field method for determining force- and
      power-velocity relationships and mechanical effectiveness of force application
      during sprint running. The proposed method, based on an inverse dynamic approach
      applied to the body center of mass, estimates the step-averaged ground reaction
      forces in runner's sagittal plane of motion during overground sprint acceleration
      from only anthropometric and spatiotemporal data. Force- and power-velocity
      relationships, the associated variables, and mechanical effectiveness were
      determined (a) on nine sprinters using both the proposed method and force plate
      measurements and (b) on six other sprinters using the proposed method during
      several consecutive trials to assess the inter-trial reliability. The low bias
      (<5%) and narrow limits of agreement between both methods for maximal horizontal
      force (638 +/- 84 N), velocity (10.5 +/- 0.74 m/s), and power output (1680 +/-
      280 W); for the slope of the force-velocity relationships; and for the mechanical
      effectiveness of force application showed high concurrent validity of the
      proposed method. The low standard errors of measurements between trials (<5%)
      highlighted the high reliability of the method. These findings support the
      validity of the proposed simple method, convenient for field use, to determine
      power, force, velocity properties, and mechanical effectiveness in sprint
      running. 

PMID- 25996965
TI  - Surprising prevalence of unrecognized vitamin D3 deficiency in fall and winter
      months in neuromuscular clinics in Central Pennsylvania: a pilot study.
AB  - OBJECTIVES: The Harvard biomarker study published in October 2013 in Neurology
      journal showed a deficiency of vitamin D in 17.6% patients with Parkinson disease
      compared with 9.3% controls (adults without neurological symptoms). Similar
      determination among neuromuscular disease patients is lacking. METHODS: A
      retrospective analysis of vitamin D levels was performed on 73 patients seen
      between September and March in the Neuromuscular Central Pennsylvania tertiary
      referral clinic. Patient selection was random. Patients with amyotrophic lateral
      sclerosis were excluded from this study. RESULTS: The prevalence of vitamin D
      deficiency was significantly above the Harvard Biomarker control values
      considering similar climatic and ethnic factors. CONCLUSIONS: Although 25-hydroxy
      D3, produced in liver and skin, can be low in fall and winter, significant lower
      levels were seen (P > 000.1) among the patients seen randomly in our
      neuromuscular clinic compared with recently published controls. Similar studies
      from different geographical zones of the Unite States considering seasonal
      influences are worth studying. Whether checking vitamin D3 blood level should
      become a standard practice is the bigger issue.

PMID- 25996966
TI  - Bortezomib-associated demyelinating neuropathy--clinical and pathologic features.
AB  - OBJECTIVES: Bortezomib is a proteasome inhibitor that is frequently used for
      multiple myeloma and lymphoma. A sensory predominant axonal neuropathy is
      associated with bortezomib treatment but a demyelinating neuropathy is also
      described primarily based on electrodiagnostic findings. We report a series of
      patients treated with bortezomib who developed peripheral neuropathy and were
      found to have demyelinating features on electrodiagnostic testing. METHODS: Four
      patients who developed a bortezomib-induced peripheral neuropathy underwent
      electrophysiological testing, and 1 patient had a nerve biopsy. RESULTS: The four
      patients with bortezomib-induced peripheral neuropathy had demyelinating features
      on their electrophysiological testing. The nerve biopsy performed in 1 patient
      demonstrated a demyelinating component in a background of axonal degeneration.
      CONCLUSIONS: Although most toxic neuropathies are symmetrical axonal
      neuropathies, bortezomib is part of a small list of agents that may cause a
      demyelinating polyneuropathy and axonal degeneration. These findings have been
      confirmed by nerve biopsy.

PMID- 25996967
TI  - IgG4-Related Neuromyopathy Associated With Recurrent Pleural Effusion.
AB  - OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is an increasingly
      recognized idiopathic systemic disorder associated with elevated serum IgG4 level
      and tissue infiltration by IgG4-positive plasma cells. Multiple neurological
      manifestations, including peripheral neuropathy, have been described in IgG4-RD.
      Our objective is to discuss a case report and review of the literature, which
      would expand the spectrum of IgG4-RD. METHODS: We describe the clinical features
      and biopsy findings in a patient with IgG4-RD who presented with features
      suggestive of neuromyopathy in the setting of recurrent pleural effusion and
      weight loss. RESULTS: Electrodiagnostic findings were suggestive of an irritable
      myopathy and polyradiculoneuropathy with primary demyelination and secondary
      axonal degeneration. Pleural biopsy and laboratory studies confirmed the
      diagnosis. Improvement was sustained with steroid therapy. CONCLUSIONS: We
      describe the first case, to our knowledge, of IgG4-related neuromyopathy
      associated with recurrent pleural effusion. Our case expands the clinical
      spectrum of IgG4-RD. Neurologists should be aware of this treatable disorder and
      in the appropriate clinical context consider it in the differential diagnosis of
      neuromyopathy.

PMID- 25996968
TI  - Severe acute inflammatory demyelinating polyradiculoneuropathy with persistent
      weakness associated with tumor-like nerve root enlargement.
AB  - We report a 23-year-old woman with rapid onset of proximal and distal limb
      weakness and areflexia, associated with tumor-like spinal nerve root enlargement
      and markedly elevated cerebrospinal fluid protein. Our patient developed the
      inability to walk within days, without preceding illness. Within two weeks, she
      had near-complete bilateral wrist and foot drop. Her cranial nerves and
      respiratory function remained intact. She received intravenous immunoglobulin
      early on for suspected Guillain-barre syndrome but remained wheelchair-bound
      until 6 Plasma exchange sessions were completed. After that, she continued to
      improve with intravenous immunoglobulin dosed every 3-4 weeks. Prominent
      demyelinating features were found on NCS, with cerebrospinal fluid protein of 415
      mg/dL. Comprehensive infectious work-up was negative. Magnetic resonance imaging
      of lumbosacral and cervical spine showed tumor-like masses mistaken for
      neurofibromatosis (axial diameter, 7.5-10 mm). Repeated magnetic resonance
      imaging 6 months later showed persistent nerve root enlargement, despite the
      patient's improved functional status. 

PMID- 25996969
TI  - West Nile Virus and MADSAM Neuropathy.

PMID- 25996970
TI  - An asymmetric sensory polyneuropathy related to thiamine deficiency from a gluten
      free diet.

PMID- 25996971
TI  - Optimizing the clinical examination of the tongue.

PMID- 25996972
TI  - Myocardial pathology associated with myasthenia gravis.

PMID- 25996974
TI  - 18F-FDG PET/CT is useful in initial staging, restaging for pediatric
      rhabdomyosarcoma.
AB  - BACKGROUND: This study aimed to evaluate 18F-fluordeoxyglucose (18F-FDG) positron
      emission tomography (PET)/computed tomography (CT) as an adjunct to CT and/or
      magnetic resonance imaging (MRI) in the staging and follow-up of pediatric
      rhabdomyosarcoma (RMS). METHODS: A total of 28 consecutive pediatric RMS (20
      males, 8 females; mean age: 4.8 years, 10 embryonal, 18 alveolar), in whom FDG
      PET/CT was performed at staging (13 patients), to evaluate the therapeutic
      effects and to follow-up (15 patients), were retrospectively included. FDG PET/CT
      was compared with MRI or CT performed with a less than a 10-day interval for
      initial staging in 13 patients. Histological data and follow-up (mean, 18 months)
      were considered as the standard of reference for result interpretation. RESULTS:
      At staging, FDG PET/CT and CT/MRI were equally effective in the detection of the
      primary RMS (accuracy, 100%). FDG PET/CT revealed metastases in lymph nodes,
      prostate, intestinal wall, chest wall and the peritoneum in 5 patients missed by
      CT or MRI, and found 41positive lymph node territories in 6 patients, 8 lung
      metastases in 3 patients and 40 lesions located in other anatomical regions
      (muscle, brain, etc.) in 4 patients versus 16, 6, and 29 for CT or MRI. In 4
      patients (31%), modifications were made and comprised 1 local therapy change and
      3 changes of systemic treatment as well. Follow-up time ranged from 3 to 48
      months, with a median follow-up time of 18 months in 15 patients for evaluation
      of therapeutic effects. Alveolar RMS (ARMS) had significantly high SUVmax, and
      more metastases was found in ARMS. CONCLUSIONS: 18F-FDG PET/CT may be useful in
      staging and restaging pediatric RMS, especially for assessing secondary lesions
      with potential therapeutic strategy alteration. The significant high SUVmax of
      ARMS and more metastases may indicate worse prognosis which needs further study.
      This study confirms that 18F-FDG PET/CT is also valuable in therapeutic
      assessment and follow-up.

PMID- 25996976
TI  - Financial Quality of Life for Patients With Cancer: An Exploratory Study.
AB  - OBJECTIVE: For people who are experiencing financial hardship, a cancer diagnosis
      can be devastating. For others, cancer may exacerbate financial stress, thereby
      influencing their livelihood, their ability to maintain employment benefits
      including health insurance, manage financial obligations, and participate
      meaningfully in cancer treatment. This study examined how vulnerabilities in
      psychosocial situations affect financial quality of life within the larger
      context of health-care decision making through a survey conducted with a cross
      sectional availability sample of 90 cancer patients. Results from the multiple
      regression analysis found that health insurance adequacy, fewer perceived
      barriers to care, and reduced financial stress are significant predictors of
      better financial quality of life in this sample. Oncology social workers and
      other disciplines involved in psychosocial treatment with patients with cancer
      must assess and address financial and logistic aspects of life in order to
      provide comprehensive cancer care that meets all needs. Collaborative
      coordination with patients with cancer and their families to intervene
      psychosocially, medically, and financially are critical components of sound
      psychosocial and medical practice.

PMID- 25996977
TI  - The long overdue inception of accreditation of centres for rectal cancer surgery
      in the United States.

PMID- 25996975
TI  - DA-Raf-Mediated Suppression of the Ras--ERK Pathway Is Essential for TGF-beta1
      Induced Epithelial-Mesenchymal Transition in Alveolar Epithelial Type 2 Cells.
AB  - Myofibroblasts play critical roles in the development of idiopathic pulmonary
      fibrosis by depositing components of extracellular matrix. One source of lung
      myofibroblasts is thought to be alveolar epithelial type 2 cells that undergo
      epithelial-mesenchymal transition (EMT). Rat RLE-6TN alveolar epithelial type 2
      cells treated with transforming growth factor-beta1 (TGF-beta1) are converted
      into myofibroblasts through EMT. TGF-beta induces both canonical Smad signaling
      and non-canonical signaling, including the Ras-induced ERK pathway (Raf-MEK-ERK).
      However, the signaling mechanisms regulating TGF-beta1-induced EMT are not fully
      understood. Here, we show that the Ras-ERK pathway negatively regulates TGF-beta1
      induced EMT in RLE-6TN cells and that DA-Raf1 (DA-Raf), a splicing isoform of A
      Raf and a dominant-negative antagonist of the Ras-ERK pathway, plays an essential
      role in EMT. Stimulation of the cells with fibroblast growth factor 2 (FGF2),
      which activated the ERK pathway, prominently suppressed TGF-beta1-induced EMT. An
      inhibitor of MEK, but not an inhibitor of phosphatidylinositol 3-kinase, rescued
      the TGF-beta1-treated cells from the suppression of EMT by FGF2. Overexpression
      of a constitutively active mutant of a component of the Ras-ERK pathway, i.e., H
      Ras, B-Raf, or MEK1, interfered with EMT. Knockdown of DA-Raf expression with
      siRNAs facilitated the activity of MEK and ERK, which were only weakly and
      transiently activated by TGF-beta1. Although DA-Raf knockdown abrogated TGF-beta1
      induced EMT, the abrogation of EMT was reversed by the addition of the MEK
      inhibitor. Furthermore, DA-Raf knockdown impaired the TGF-beta1-induced nuclear
      translocation of Smad2, which mediates the transcription required for EMT. These
      results imply that intrinsic DA-Raf exerts essential functions for EMT by
      antagonizing the TGF-beta1-induced Ras-ERK pathway in RLE-6TN cells. 

PMID- 25996982
TI  - Sleep duration and snoring associate with hypertension and glycaemic control in
      patients with diabetes.
AB  - AIMS: Few studies have analysed the effect of sleep duration and snoring on
      hypertension and glycaemic control in patients with diabetes. This study aims to
      investigate the relationship of sleep duration and snoring on prevalent
      hypertension and glycaemic control in people with diabetes. METHODS: In the
      baseline survey of the REACTION study, 56 032 patients with diabetes were
      categorized into four groups according to self-reported sleep duration: < 6, 6
      7.9, 8-8.9 and >= 9 h. Snoring frequency was evaluated as 'usually',
      'occasionally' or 'never'. Hypertension was assessed by systolic blood pressure,
      diastolic blood pressure, self-reported previous diagnosis and antihypertensive
      medications. 'Good' glycaemic control was defined as HbA1c < 53 mmol/mol (7.0%)
      and 'poor' glycaemic control as HbA1c >= 53 mmol/mol (7.0%). RESULTS: Controlling
      for potential confounders and intermediates, sleep >= 9 h relative to
      intermediate sleep (6-7.9 h) was significantly associated with prevalent
      hypertension (OR: 1.25, 95% CI: 1.18-1.32) and poor glycaemic control (OR: 1.11,
      95% CI: 1.05-1.18), and a U-shaped association was found between sleep duration
      and prevalent hypertension (P for quadratic trend = 0.019). Usually snoring was
      positively associated with prevalent hypertension (OR: 1.30, 95% CI: 1.23-1.37),
      whereas the association between snoring and poor glycaemic control was only on
      the borderline of statistical significance. CONCLUSIONS: Compared with a sleep
      duration of 6-7.9 h, longer sleep duration was associated with a higher
      prevalence of hypertension and poor glycaemic control in people with diabetes.
      Moreover, the relationship between sleep duration and prevalent hypertension was
      U-shaped. These findings may propose important public health implications for
      diabetes management.

PMID- 25996983
TI  - The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism
      Independent of gD Activation by Its Receptors.
AB  - Herpes simplex virus (HSV) enters cells by means of four essential glycoproteins 
      gD, gH/gL, gB, activated in a cascade fashion by gD binding to one of its
      receptors, nectin1 and HVEM. We report that the engineering in gH of a
      heterologous ligand - a single-chain antibody (scFv) to the cancer-specific HER2
      receptor - expands the HSV tropism to cells which express HER2 as the sole
      receptor. The significance of this finding is twofold. It impacts on our
      understanding of HSV entry mechanism and the design of retargeted oncolytic-HSVs.
      Specifically, entry of the recombinant viruses carrying the scFv-HER2-gH chimera
      into HER2+ cells occurred in the absence of gD receptors, or upon deletion of key
      residues in gD that constitute the nectin1/HVEM binding sites. In essence, the
      scFv in gH substituted for gD-mediated activation and rendered a functional gD
      non-essential for entry via HER2. The activation of the gH moiety in the chimera
      was carried out by the scFv in cis, not in trans as it occurs with wt-gD. With
      respect to the design of oncolytic-HSVs, previous retargeting strategies were
      based exclusively on insertion in gD of ligands to cancer-specific receptors. The
      current findings show that (i) gH accepts a heterologous ligand. The viruses
      retargeted via gH (ii) do not require the gD-dependent activation, and (iii)
      replicate and kill cells at high efficiency. Thus, gH represents an additional
      tool for the design of fully-virulent oncolytic-HSVs retargeted to cancer
      receptors and detargeted from gD receptors. 

PMID- 25996984
TI  - Effect of the Healthy Schools Program on prevalence of overweight and obesity in
      California schools, 2006-2012.
AB  - INTRODUCTION: The Alliance for a Healthier Generation's Healthy Schools Program
      (HSP) is a national evidence-based obesity-prevention initiative aimed at
      providing the schools in greatest need with onsite training and technical
      assistance (TTA) and consultation with national experts (HSP national advisors)
      to create sustainable healthy change in schools' nutrition and physical activity
      environments. The objective of this study was to evaluate the impact of HSP on
      the prevalence of overweight and obesity in California schools, from HSP's
      inception in 2006 through 2012. METHODS: We used statewide body mass index (BMI)
      data collected annually from 5th-, 7th-, and 9th-grade students to determine
      whether enrolling in the HSP's onsite intervention reduced the prevalence of
      overweight and obesity in intervention schools (n = 281) versus propensity-score
      matched control schools (n = 709) and whether increasing exposure to the program
      (TTA and contact with HSP national advisors) was associated with reductions in
      the prevalence of overweight and obesity. RESULTS: Analyses showed no difference
      between HSP schools and control schools in overweight or obesity prevalence.
      However, program exposure varied widely among participating schools, and each
      additional contact with TTA or HSP national advisors was associated with a 0.3%
      decline in overweight and obesity prevalence (P < .05). CONCLUSION: HSP appears
      to be an important means of supporting schools in reducing obesity. Although
      participation in HSP alone was not sufficient to improve weight status in
      California schools, there was a clear dose-response relationship to the program.
      HSP serves as an effective model for addressing childhood obesity among engaged
      schools.

PMID- 25996985
TI  - Erratum, vol. 12, April 30 release. Getting research to the policy table: a
      qualitative study with public health researchers on engaging with policy makers.

PMID- 25996986
TI  - Community-based restaurant interventions to promote healthy eating: a systematic
      review.
AB  - INTRODUCTION: Eating in restaurants is associated with high caloric intake. This
      review summarizes and evaluates the evidence supporting community-based
      restaurant interventions. METHODS: We searched all years of PubMed and Web of
      Knowledge through January 2014 for original articles describing or evaluating
      community-based restaurant interventions to promote healthy eating. We extracted
      summary information and classified the interventions into 9 categories according
      to the strategies implemented. A scoring system was adapted to evaluate the
      evidence, assigning 0 to 3 points to each intervention for study design, public
      awareness, and effectiveness. The average values were summed and then multiplied
      by 1 to 3 points, according to the volume of research available for each
      category. These summary scores were used to determine the level of evidence
      (insufficient, sufficient, or strong) supporting the effectiveness of each
      category. RESULTS: This review included 27 interventions described in 25 studies
      published since 1979. Most interventions took place in exclusively urban areas of
      the United States, either in the West or the South. The most common intervention
      categories were the use of point-of-purchase information with promotion and
      communication (n = 6), and point-of-purchase information with increased
      availability of healthy choices (n = 6). Only the latter category had sufficient
      evidence. The remaining 8 categories had insufficient evidence because of
      interventions showing no, minimal, or mixed findings; limited reporting of
      awareness and effectiveness; low volume of research; or weak study designs. No
      intervention reported an average negative impact on outcomes. CONCLUSION:
      Evidence about effective community-based strategies to promote healthy eating in
      restaurants is limited, especially for interventions in rural areas. To expand
      the evidence base, more studies should be conducted using robust study designs,
      standardized evaluation methods, and measures of sales, behavior, and health
      outcomes.

PMID- 25996987
TI  - Psychosocial constructs and postintervention changes in physical activity and
      dietary outcomes in a lifestyle intervention, HUB City Steps, 2010.
AB  - INTRODUCTION: Although modifications to dietary and physical activity (PA)
      behavior can reduce blood pressure, racial disparities in prevalence and control
      of hypertension persist. Psychosocial constructs (PSCs) of self-regulation,
      processes of change, and social support are associated with initiation and
      maintenance of PA in African Americans; which PSCs best predict lifestyle
      behavior changes is unclear. This study's objective was to examine relationships
      among PSC changes and postintervention changes in PA and dietary outcomes in a
      community-based, multicomponent lifestyle intervention. METHODS: This study was a
      noncontrolled, pre/post experimental intervention conducted in a midsized,
      Southern US city in 2010. Primarily African American adults (n = 269)
      participated in a 6-month intervention consisting of motivational enhancement,
      social support, pedometer diary self-monitoring, and 5 education sessions.
      Outcome measures included pedometer-determined steps per day, fitness, dietary
      intake, and PSC measures. Generalized linear mixed models were used to test for
      postintervention changes in behavioral outcomes, identify predictors of PSC
      changes, and determine if PSC changes predicted changes in PA and diet. RESULTS:
      Postintervention changes were apparent for 10 of 24 PSCs (P < .05). Processes of
      change components, including helping relationships, reinforcement management, and
      consciousness raising, were significant predictors of fitness change (P < .05).
      CONCLUSION: This article is among the first to address how measures of several
      theoretical frameworks of behavior change influence changes in PA and dietary
      outcomes in a multicomponent, community-based, lifestyle intervention conducted
      with African American adults. Findings reported identify PSC factors on which
      health behavior interventions can focus.

PMID- 25996989
TI  - Quantitative R2* MRI of the liver with rician noise models for evaluation of
      hepatic iron overload: Simulation, phantom, and early clinical experience.
AB  - PURPOSE: To compare Rician and non-Rician noise models for quantitative R2 *
      magnetic resonance imaging (MRI), in a simulation, phantom, and human study.
      MATERIALS AND METHODS: Synthetic 12-echo spoiled GRE (SGRE) datasets were
      generated with various R2 * rates (0-2000 sec(-1) ) at a signal-to-noise ratio
      (SNR) of 50, 20, 10, and 5. Phantoms of different MnCl2 concentrations (0-25 mM)
      were constructed and imaged using a 12-echo 3D SGRE sequence at 1.5T. Increasing
      levels of synthetic noise was added to the original data to simulate sequentially
      lower SNR conditions. Sixteen patients with suspected or known iron overload were
      imaged using 12-echo 3D SGRE at 1.5T. Various R2 * quantification methods, based
      on Rician and non-Rician noise models, were compared in the simulation, phantom,
      and human datasets. RESULTS: Non-Rician R2 * estimates were variably inaccurate
      in the high R2 * range (>500 sec(-1) ), with SNR-dependent linear goodness-of-fit
      statistic (R(2) ) of 0.373-0.999. Rician R2 * estimates were accurate even in the
      high R2 * range, with high R(2) of 0.940-0.999 regardless of SNR. Non-Rician R2 *
      estimates were variably nonlinear at high MnCl2 concentrations, with SNR
      dependent R(2) of 0.345-0.994. Rician R2 * estimates were linear even at high
      MnCl2 concentrations, with high R(2) of 0.923-0.994 regardless of SNR. Between
      method agreement of the R2 * estimates was excellent in patients with low
      ferritin but poor in patients with high ferritin. Rician R2 * estimates had
      excellent correlation with ferritin (r = 0.966 P < 0.001). CONCLUSION: Rician R2
      * estimates were most consistent in the high R2 * conditions and under varying
      SNR, and may be more reliable when high iron load is suspected.

PMID- 25996988
TI  - Colonoscopy screening among US adults aged 40 or older with a family history of
      colorectal cancer.
AB  - INTRODUCTION: Colonoscopy screening reduces colorectal cancer (CRC) incidence and
      mortality. CRC screening is recommended at age 50 for average-risk people.
      Screening of first-degree relatives of CRC patients is recommended to begin at
      age 40 or 10 years before the age at diagnosis of the youngest relative diagnosed
      with CRC. CRC incidence has increased recently among younger Americans while it
      has declined among older Americans. The objective of this study was to determine
      whether first-degree relatives of CRC patients are being screened according to
      recommended guidelines. METHODS: We studied colonoscopy screening rates among the
      US population reporting a CRC family history using 2005 and 2010 National Health
      Interview Survey data. RESULTS: Of 26,064 study-eligible respondents, 2,470
      reported a CRC family history; of those with a family history, 45.6% had a
      colonoscopy (25.2% in 2005 and 65.8% 2010). The colonoscopy rate among first
      degree relatives aged 40 to 49 in 2010 (38.3%) was about half that of first
      degree relatives aged 50 or older (69.7%). First-degree relatives were nearly
      twice as likely as nonfirst-degree relatives to have a colonoscopy (adjusted odds
      ratio [AOR], 1.7; 95% confidence interval, 1.5-1.9), but those aged 40 to 49 were
      less likely to have a colonoscopy than those in older age groups (AOR, 2.6 for
      age 50-64; AOR, 3.6 for age >=65). Interactions with age, insurance, and
      race/ethnicity were not significant. Having health insurance tripled the
      likelihood of screening. CONCLUSION: Despite a 5-fold increase in colonoscopy
      screening rates since 2005, rates among first-degree relatives younger than the
      conventional screening age have lagged. Screening promotion targeted to this
      group may halt the recent rising trend of CRC among younger Americans.

PMID- 25996990
TI  - Effect of long-term organic removal on ion exchange properties and performance
      during sewage tertiary treatment by conventional anion exchange resins.
AB  - This study evaluated the long-term dissolved organic matter (DOM), phosphorus and
      nitrogen removal performance of a commercially available conventional anion
      exchange resin (AER) from actual secondary effluent (SE) in a sewage treatment
      plant based on a pilot-scale operation (2.2 m(3) d(-1), 185 cycles, 37,000 bed
      volume, 1.5 years). Particular emphasis was given to the potential effect of DOM
      fouling on the ion exchange properties and performance during the long-term
      operation. Despite the large range of COD (15.6-33.5 mg L(-1)), BOD5 (3.0-5.6 mg
      L(-1)), DOC (6.5-24.2 mg L(-1)), and UV254 (UV absorption at 254 nm) (0.108-0.229
      cm(-1)) levels in the SE, the removal efficiencies of the AER for the
      aforementioned parameters were 43+/-12%, 46+/-15%, 45+/-9%, and 72+/-4%,
      respectively. Based on three-dimensional fluorescence excitation-emission matrix
      data, i.e., the fluorescence intensities of four regions (peaks A-D), all organic
      components of the SE were effectively removed (peak A 74%, peak B 48%, peak C
      55%, and peak D 45%) following the adsorption. The AER effluent still has
      considerable polycyclic aromatic hydrocarbons' ecological hazard on freshwater
      fishes when they were significantly removed from SE. The obvious DOM fouling on
      the AER, identified by color change, had no significant influence on the long
      term removal of the representative inorganic anions (averaging 95+/-4% phosphate,
      100+/-0% SO4(2-), and 62+/-17% NO3(-)) and AER properties (including total
      exchange capacity, moisture content, and true density). The conventional AER can
      produce high quality reclaimed water from SE at a low operational cost.

PMID- 25996991
TI  - Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory
      Glaucoma in the Mainland Chinese Population.
AB  - BACKGROUND: To evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV)
      and the risk factors associated with AGV implantation failure in a population of
      Chinese patients with refractory glaucoma. METHOD: In total, 79 eyes with
      refractory glaucoma from 79 patients treated in our institution from November
      2007 to November 2010 were enrolled in this retrospective study. The demographic
      data, preoperative and postoperative intraocular pressures (IOPs), best corrected
      visual acuity (BCVA), number of anti-glaucoma medications used, completed and
      qualified surgery success rates and postoperative complications were recorded to
      evaluate the outcomes of AGV implantation. Factors that were associated with
      implant failure were determined using Cox proportional hazard regression model
      analysis and multiple linear regression analysis. PRINCIPLE FINDINGS: The average
      follow-up time was 12.7+/-5.8 months (mean+/-SD). We observed a significant
      reduction in the mean IOP from 39.9+/-12.6 mm Hg before surgery to 19.3+/-9.6 mm
      Hg at the final follow-up. The complete success rate was 59.5%, and the qualified
      success rate was 83.5%. The number of previous surgeries was negatively
      correlated with qualified success rate (P<0.05, OR=0.736, 95% CI 0.547-0.99).
      Patients with previous trabeculectomy were more likely to use multiple anti
      glaucoma drugs to control IOP (P<0.01). The primary complication was determined
      to be a flat anterior chamber (AC). CONCLUSION: AGV implantation was safe and
      effective for the management of refractory glaucoma. Patients with a greater
      number of previous surgeries were more likely to experience surgical failure, and
      patients with previous trabeculectomy were more likely to use multiple anti
      glaucoma drugs to control postoperative IOP.

PMID- 25996996
TI  - Positron Emission Tomography studies with [11C]PBR28 in the Healthy Rodent Brain:
      Validating SUV as an Outcome Measure of Neuroinflammation.
AB  - Molecular imaging of the 18 kD Translocator protein (TSPO) with positron emission
      tomography (PET) is of great value for studying neuroinflammation in rodents
      longitudinally. Quantification of the TSPO in rodents is, however, quite
      challenging. There is no suitable reference region and the use of plasma-derived
      input is not an option for longitudinal studies. The aim of this study was
      therefore to evaluate the use of the standardized uptake value (SUV) as an
      outcome measure for TSPO imaging in rodent brain PET studies, using [11C]PBR28.
      In the first part of the study, healthy male Wistar rats (n = 4) were used to
      determine the correlation between the distribution volume (VT, calculated with
      Logan graphical analysis) and the SUV. In the second part, healthy male Wistar
      rats (n = 4) and healthy male C57BL/6J mice (n = 4), were used to determine the
      test-retest variability of the SUV, with a 7-day interval between measurements.
      Dynamic PET scans of 63 minutes were acquired with a nanoScan PET/MRI and
      nanoScan PET/CT. An MRI scan was made for anatomical reference with each
      measurement. The whole brain VT of [11C]PBR28 in rats was 42.9 +/- 1.7. A
      statistically significant correlation (r2 = 0.96; p < 0.01) was found between the
      VT and the SUV. The test-retest variability in 8 brain region ranged from 8 to
      20% in rats and from 7 to 23% in mice. The interclass correlation coefficient
      (ICC) was acceptable to excellent for rats, but poor to acceptable for mice. IN
      CONCLUSION: The SUV of [11C]PBR28 showed a high correlation with VT as well as
      good test-retest variability. For future longitudinal small animal PET studies
      the SUV can thus be used to describe [11C]PBR28 uptake in healthy brain tissue.
      Based on the present observations, further studies are needed to explore the
      applicability of this approach in small animal disease models, with special
      regard to neuroinflammatory models.

PMID- 25996997
TI  - Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation
      protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.
AB  - Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA
      plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV)
      or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for
      EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual
      vaccines elicited slightly higher IgG responses to EBOV or MARV than did the
      combination vaccines. No significant differences in immune responses of macaques
      given the individual or combination vaccines were measured by pseudovirion
      neutralization or IFN-gamma ELISpot assays. Both the MARV and mixed vaccines were
      able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a
      greater proportion of macaques vaccinated with the EBOV vaccine survived lethal
      EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs.
      1/6). EBOV challenge survivors had significantly higher pre-challenge
      neutralizing antibody titers than those that succumbed.

PMID- 25996998
TI  - Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks
      (DSBs) Using gamma-H2AX Immunofluorescence Microscopy in a Preliminary Study.
AB  - BACKGROUND: Radiation exposure occurs in X-ray guided interventional procedures
      or computed tomography (CT) and gamma-H2AX-foci are recognized to represent DNA
      double-strand breaks (DSBs) as a biomarker for radiation induced damage.
      Antioxidants may reduce the induction of gamma-H2AX-foci by binding free
      radicals. The aim of this study was to establish a dose-effect relationship and a
      time-effect relationship for the individual antioxidants on DSBs in human blood
      lymphocytes. MATERIALS AND METHODS: Blood samples from volunteers were irradiated
      with 10 mGy before and after pre-incubation with different antioxidants (zinc,
      trolox, lipoic acid, beta-carotene, selenium, vitamin E, vitamin C, N-acetyl-L
      cysteine (NAC) and Q 10). Thereby, different pre-incubation times, concentrations
      and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes
      were stained against the phosphorylated histone variant gamma-H2AX. RESULTS: For
      zinc, trolox and lipoic acid regardless of concentration or pre-incubation time,
      no significant decrease of gamma-H2AX-foci was found. However, beta-carotene
      (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%)
      led to a significant reduction of gamma-H2AX-foci at a pre-incubation time of 1
      hour. The combination of different antioxidants did not have an additive effect.
      CONCLUSION: Antioxidants administered prior to irradiation demonstrated the
      potential to reduce gamma-H2AX-foci in blood lymphocytes.

PMID- 25996999
TI  - Mortality, temporary sterilization, and maternal effects of sublethal heat in bed
      bugs.
AB  - Adult bed bugs were exposed to the sublethal temperatures 34.0 degrees C, 35.5
      degrees C, 37.0 degrees C, 38.5 degrees C, or 40.0 degrees C for 3, 6, or 9 days.
      The two uppermost temperatures induced 100% mortality within 9 and 2 days,
      respectively, whereas 34.0 degrees C had no observable effect. The intermediate
      temperatures interacted with time to induce a limited level of mortality but had
      distinct effects on fecundity, reflected by decreases in the number of eggs
      produced and hatching success. Adult fecundity remained low for up to 40 days
      after heat exposure, and the time until fertility was restored correlated with
      the temperature-sum experienced during heat exposure. Three or 6 days of parental
      exposure to 38.5 degrees C significantly lowered their offspring's feeding and
      moulting ability, which consequently led to a failure to continue beyond the
      third instar. Eggs that were deposited at 22.0 degrees C before being exposed to
      37.0 degrees C for 3 or 6 days died, whereas eggs that were exposed to lower
      temperatures were not significantly affected. Eggs that were deposited during
      heat treatment exhibited high levels of mortality also at 34.0 degrees C and 35.5
      degrees C. The observed negative effects of temperatures between 34.0 degrees C
      and 40.0 degrees C may be utilized in pest management, and sublethal temperature
      exposure ought to be further investigated as an additional tool to decimate or
      potentially eradicate bed bug populations. The effect of parental heat exposure
      on progeny demonstrates the importance of including maternal considerations when
      studying bed bug environmental stress reactions. 

PMID- 25997000
TI  - Elderly donor liver grafts are not associated with a higher incidence of biliary
      complications after liver transplantation: results of a national multicenter
      study.
AB  - BACKGROUND: Liver transplantation with livers grafts from elderly donors has been
      associated with a higher risk of biliary complications. The aim of this study was
      to examine whether our national protocol could contribute to a lower incidence of
      biliary complications. METHODS: All adult recipients in the Netherlands
      transplanted with a liver from an elderly donor (>= 65 yrs; n = 68) in the period
      January 2000-July 2011 were matched with recipients of a liver from a donor <65
      yr (n = 136). Outcome parameters were 90-d, one-yr, and three-yr patient/graft
      survival rates, biliary complications (non-anastomotic stricture, anastomotic
      stricture, biliary leakage, and post-transplant cholangitis), and postoperative
      hepatic ischemic injury serum markers (AST/ALT). RESULTS: The median cold
      ischemia time (CIT) was 7:25 (h:min) in the group recipients of an elderly donor
      liver graft. Ninety-day, one-yr, and three-yr patient/graft survival rates were
      similar between the group with an elderly donor liver and their younger controls.
      Moreover, no differences were found in the incidence of biliary complications and
      postoperative levels of AST/ALT between the two groups. CONCLUSION:
      Transplantation of livers from elderly donors (>= 65 yr) is not associated with a
      higher incidence of biliary complications, in a national policy wherein the CIT
      is kept short.

PMID- 25997001
TI  - A solid-state NMR study of selenium substitution into nanocrystalline
      hydroxyapatite.
AB  - The substitution of selenium oxyanions in the hydroxyapatite structure was
      examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study
      was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X
      ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate
      (HA300-1.2SeO4) or selenite (HA300-1.2SeO3) substituted hydroxyapatites were
      synthesized using the standard wet method and heated at 300  degrees C to remove
      loosely bonded water. PXRD data showed that all samples are single-phase,
      nanocrystalline hydroxyapatite. The incorporation of selenite and selenate ions
      affected the lattice constants. In selenium-containing samples the concentration
      of Se was very similar and amounted to 9.55% and 9.64%, for HA300-1.2SeO4 and
      HA300-1.2SeO3, respectively. PXRD and ssNMR data showed that the selenite doping
      significantly decreases the crystallite size and crystallinity degree. 31P and 1H
      NMR experiments demonstrated the developed surface hydrated layer in all samples,
      especially in HA300-1.2SeO3. 1H NMR studies showed the dehydroxylation of HA
      during the selenium oxyanions substitution and the existence of hydrogen bonding
      in structural hydroxyl group channels. 1H->77Se cross polarization NMR
      experiments indicated that selenites and selenates are located in the crystal
      lattice and on the crystal surface. 

PMID- 25997002
TI  - Gene expression signature in endemic osteoarthritis by microarray analysis.
AB  - Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown
      pathogenesis. Diagnosis of KBD is effective only in advanced cases, which
      eliminates the possibility of early treatment and leads to an inevitable
      exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based
      gene signature for the detection of KBD. Previously published gene expression
      profile data on cartilage and peripheral blood mononuclear cells (PBMCs) from
      adults with KBD were compared to select potential target genes. Microarray
      analysis was conducted to evaluate the expression of the target genes in a cohort
      of 100 KBD patients and 100 healthy controls. A gene expression signature was
      identified using a training set, which was subsequently validated using an
      independent test set with a minimum redundancy maximum relevance (mRMR) algorithm
      and support vector machine (SVM) algorithm. Fifty unique genes were
      differentially expressed between KBD patients and healthy controls. A 20-gene
      signature was identified that distinguished between KBD patients and controls
      with 90% accuracy, 85% sensitivity, and 95% specificity. This study identified a
      20-gene signature that accurately distinguishes between patients with KBD and
      controls using peripheral blood samples. These results promote the further
      development of blood-based genetic biomarkers for detection of KBD. 

PMID- 25997003
TI  - Anti-Fibrotic Effects of Class I HDAC Inhibitor, Mocetinostat Is Associated with
      IL-6/Stat3 Signaling in Ischemic Heart Failure.
AB  - BACKGROUND: Recent studies have linked histone deacetylases (HDAC) to remodeling
      of the heart and cardiac fibrosis in heart failure. However, the molecular
      mechanisms linking chromatin remodeling events with observed anti-fibrotic
      effects are unknown. Here, we investigated the molecular players involved in anti
      fibrotic effects of HDAC inhibition in congestive heart failure (CHF) myocardium
      and cardiac fibroblasts in vivo. METHODS AND RESULTS: MI was created by coronary
      artery occlusion. Class I HDACs were inhibited in three-week post MI rats by
      intraperitoneal injection of Mocetinostat (20 mg/kg/day) for duration of three
      weeks. Cardiac function and heart tissue were analyzed at six week post-MI. CD90+
      cardiac fibroblasts were isolated from ventricles through enzymatic digestion of
      heart. In vivo treatment of CHF animals with Mocetinostat reduced CHF-dependent
      up-regulation of HDAC1 and HDAC2 in CHF myocardium, improved cardiac function and
      decreased scar size and total collagen amount. Moreover, expression of pro
      fibrotic markers, collagen-1, fibronectin and Connective Tissue Growth Factor
      (CTGF) were reduced in the left ventricle (LV) of Mocetinostat-treated CHF
      hearts. Cardiac fibroblasts isolated from Mocetinostat-treated CHF ventricles
      showed a decrease in expression of collagen I and III, fibronectin and Timp1. In
      addition, Mocetinostat attenuated CHF-induced elevation of IL-6 levels in CHF
      myocardium and cardiac fibroblasts. In parallel, levels of pSTAT3 were reduced
      via Mocetinostat in CHF myocardium. CONCLUSIONS: Anti-fibrotic effects of
      Mocetinostat in CHF are associated with the IL-6/STAT3 signaling pathway. In
      addition, our study demonstrates in vivo regulation of cardiac fibroblasts via
      HDAC inhibition.

PMID- 25997004
TI  - Microwave-Assisted Synthesis of Glutathione-Capped CdTe/CdSe Near-Infrared
      Quantum Dots for Cell Imaging.
AB  - These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD)
      nanoparticles in aqueous solution were synthesized using a microwave-assisted
      approach. The prepared type II core/shell QD nanoparticles were characterized by
      UV-Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction
      (XRD) and high-resolution transmission electron microscopy (HR-TEM). Results
      revealed that the QD nanoparticles exhibited good dispersity, a uniform size
      distribution and tunable fluorescence emission in the near-infrared (NIR) region.
      In addition, these nanoparticles exhibited good biocompatibility and
      photoluminescence in cell imaging. In particular, this type of core/shell NIR QDs
      may have potential applications in molecular imaging. 

PMID- 25997005
TI  - Periodic CO2 Dosing Strategy for Dunaliella salina Batch Culture.
AB  - A periodic CO2 dosing strategy for D. salina 19/30 batch culture is proposed. A
      model of periodic CO2 dosing including dosing time calculation, dosing interval
      estimation and final chlorophyll yield prediction was established. In
      experiments, 5% CO2/95% N2 gas was periodically dosed into D. salina culture. Two
      different gas dosing flow rates were tested. The corresponding dosing time for
      each flow rate was estimated via the model (10 min.d-1 for 0.7 L.min-1 and 36
      min.d-1 for 0.3 L.min-1). Daily pH measurements showed that the pH of these
      cultures dosed periodically was always kept between 7.5 and 9.5, which highlights
      that periodic gas supply can maintain a suitable range of pH for microalgal
      growth without expensive buffers. Notably the culture dosed for set daily
      intervals was seen to have similar growth to the culture supplied constantly, but
      with much higher CO2 capture efficiency (11%-18%) compared to continuous dosing
      (0.25%). It shows great potential for using periodic gas supply to reduce cost,
      wasted gas and energy use. 

PMID- 25997007
TI  - Investigation of in situ and ex situ catalytic pyrolysis of miscanthus *
      giganteus using a PyGC-MS microsystem and comparison with a bench-scale spouted
      bed reactor.
AB  - The objective of the present work is to explore the particularities of a micro
      scale experimental apparatus with regards to the study of catalytic fast
      pyrolysis (CFP) of biomass. In situ and ex situ CFP of miscanthus * giganteus
      were performed with ZSM-5 catalyst. Higher permanent gas yields and higher
      selectivity to aromatics in the bio-oil were observed from ex situ CFP, but
      higher bio-oil yields were recorded during in situ CFP. Solid yields were
      comparable across both configurations. The results from in situ and ex situ PyGC
      were also compared with the product yields and selectivities obtained using a
      bench-scale, spouted-bed reactor. The bio-oil composition and overall product
      distribution for the PyGC ex situ configuration more closely resembled that of
      the spouted-bed reactor. The coke/char from in situ CFP in the PyGC was very
      similar in nature to that obtained from the spouted-bed reactor. 

PMID- 25997006
TI  - Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform.
AB  - Mutations of the SHANK3 gene have been associated with autism spectrum disorder.
      Individuals harboring different SHANK3 mutations display considerable
      heterogeneity in their cognitive impairment, likely due to the high SHANK3
      transcriptional diversity. In this study, we report a novel interaction between
      the Mutated in colorectal cancer (MCC) protein and a newly identified SHANK3
      protein isoform in human colon cancer cells and mouse brain tissue. Hence, our
      proteogenomic analysis identifies a new human long isoform of the key synaptic
      protein SHANK3 that was not predicted by the human reference genome. Taken
      together, our findings describe a potential new role for MCC in neurons, a new
      human SHANK3 long isoform and, importantly, highlight the use of proteomic data
      towards the re-annotation of GC-rich genomic regions. 

PMID- 25997008
TI  - New energy crop giant cane (Arundo donax L.) can substitute traditional energy
      crops increasing biogas yield and reducing costs.
AB  - Giant cane is a promising non-food crop for biogas production. Giant cane and
      corn silages coming from full-scale fields were tested, in mixtures with pig
      slurry, for biomethane production by a continuous stirred tank lab-scale-reactor
      (CSTR) approach. Results indicated that giant cane produced less biomethane than
      corn, i.e. 174+/-10 N m(3) CH4 Mg(-1) TS(-1) and 245+/-26 N m(3) CH4 Mg(-1) TS(
      1), respectively. On the other hand, because of its high field biomass
      production, the biogas obtainable per Ha was higher for giant cane than for corn,
      i.e. 12,292 N m(3) CH4 Ha(-1) and 4549 N m(3) CH4 Ha(-1), respectively. Low
      energetic and agronomic inputs for giant cane cultivation led to a considerable
      reduction in the costs of producing both electricity and biomethane, i.e. 0.50 ?
      N m(-3) CH4(-1) and 0.81 ? N m(-3) CH4(-1), and 0.10 ? kW hEE(-1) and 0.19 ? kW
      hEE(-1) for biomethane and electricity production, and for giant cane and corn
      mixtures respectively.

PMID- 25997009
TI  - Grindability and combustion behavior of coal and torrefied biomass blends.
AB  - Biomass samples (pine, black poplar and chestnut woodchips) were torrefied to
      improve their grindability before being combusted in blends with coal.
      Torrefaction temperatures between 240 and 300  degrees C and residence times
      between 11 and 43 min were studied. The grindability of the torrefied biomass,
      evaluated from the particle size distribution of the ground sample, significantly
      improved compared to raw biomass. Higher temperatures increased the proportion of
      smaller-sized particles after grinding. Torrefied chestnut woodchips (280 
      degrees C, 22 min) showed the best grinding properties. This sample was blended
      with coal (5-55 wt.% biomass). The addition of torrefied biomass to coal up to 15
      wt.% did not significantly increase the proportion of large-sized particles after
      grinding. No relevant differences in the burnout value were detected between the
      coal and coal/torrefied biomass blends due to the high reactivity of the coal. NO
      and SO2 emissions decreased as the percentage of torrefied biomass in the blend
      with coal increased.

PMID- 25997010
TI  - Effect of sodium accumulation on heterotrophic growth and polyhydroxybutyrate
      (PHB) production by Cupriavidus necator.
AB  - This study evaluates the effect of sodium (Na(+)) concentration on the growth and
      PHB production by Cupriavidus necator. Both biomass growth and PHB production
      were inhibited by Na(+): biomass growth became zero at 8.9 g/L Na(+)
      concentration while PHB production was completely stopped at 10.5 g/L Na(+). A
      mathematical model for pure culture heterotrophic PHB production was set up to
      describe the Na(+) inhibition effect. The parameters related to Na(+) inhibition
      were estimated based on shake flask experiments. The accumulated Na(+) showed non
      linear inhibition effect on biomass growth but linear inhibition effect on PHB
      production kinetics. Fed-batch experiments revealed that a high accumulation of
      Na(+) due to a prolonged growth phase, using NaOH for pH control, decreased the
      subsequent PHB production. The model was validated based on independent
      experimental data sets, showing a good agreement between experimental data and
      simulation results.

PMID- 25997011
TI  - Effect of light intensity on physiological changes, carbon allocation and neutral
      lipid accumulation in oleaginous microalgae.
AB  - Chlorella sp. and Monoraphidium sp. were the potential microalgal species for
      lipid production. This study aimed to investigate different light intensities
      (40, 200, 400 MUmol photon m(-2) s(-1)) on physiological changes, photosynthetic
      carbon partitioning and neutral lipid accumulation in both microalgae. Results
      suggested that under high light (HL, 400 MUmol photon m(-2) s(-1)), chlorophyll
      degraded, protein and carbohydrate content decreased; more carbon allocated into
      lipid as well as most of intracellular space was occupied by lipid bodies.
      Moreover, with the lipid accumulation, Fv/Fm decreased and ROS scavenging enzyme
      increased. Membrane lipid reduced dramatic (29.73-37.97%) to format NL (71.66% of
      total lipid in Chlorella sp. L1 and 60.65% in Monoraphidium dybowskii Y2). The NL
      productivity under HL (51.36 and 49.71 mg L(-1) d(-1)) were more than 3 times of
      those under LL. Additionally, FAME profiles proved that the useful fatty acid
      components for biodiesel production were enhanced under HL.

PMID- 25997012
TI  - Hydrolysis behavior of regenerated celluloses with different degree of
      polymerization under microwave radiation.
AB  - This work studied the hydrolysis behavior of regenerated celluloses (RCs) with
      different degree of polymerization (DP) by using the catalyst of dilute acid
      under microwave radiation. Results showed that the DP had a considerable
      influence on hydrolysis of cellulose. The reactivity of RCs was significantly
      improved when DP was lower than 51. The highest sugar yield of 59.2% was achieved
      from RC with lowest DP of 23 at 160  degrees C for 15 min. But the lowest yield
      of 32.6% was obtained when RC with highest DP of 132 was used. Recrystallization
      of cellulose was found to hinder the further hydrolysis particularly with the
      high DP. The effect of recrystallization can be reduced by the decrease of DP of
      RCs. This research demonstrates that the DP of RCs plays a crucial role on
      hydrolysis and it provides a preliminary guide based on DP to find a suitable
      pretreatment method for cellulose hydrolysis.

PMID- 25997013
TI  - Optimization of isolation and cultivation of bacterial endophytes through
      addition of plant extract to nutrient media.
AB  - Many endophytes have beneficial effects on plants and can be exploited in
      biotechnological applications. Studies hypothesize that only 0.001-1% of all
      plant-associated bacteria are cultivable. Moreover, even after successful
      isolations, many endophytic bacteria often show reduced regrowth capacity. This
      research aimed to optimize isolation processes and culturing these bacteria
      afterwards. We compared several minimal and complex media in a screening. Beside
      the media themselves, two gelling agents and adding plant extract to media were
      investigated to enhance the number and diversity of endophytes as well as the
      growth capacity when regrown after isolation. In this work, 869 medium delivered
      the highest numbers of cultivable bacteria, as well as the highest diversity.
      When comparing gelling agents, no differences were observed in the numbers of
      bacteria. Adding plant extract to the media lead to a slight increase in
      diversity. However, when adding plant extract to improve the regrowth capacity,
      sharp increases of viable bacteria occurred in both rich and minimal media. 

PMID- 25997015
TI  - Electrical signals in prayer plants (marantaceae)? Insights into the trigger
      mechanism of the explosive style movement.
AB  - The explosive pollination mechanism of the prayer plants (Marantaceae) is unique
      among plants. After a tactile stimulus by a pollinator, the style curls up
      rapidly and mediates pollen exchange. It is still under discussion whether this
      explosive movement is released electrophysiologically, i.e. by a change in the
      membrane potential (as in Venus flytrap), or purely mechanically. In the present
      study, electrophysiological experiments are conducted to clarify the mechanism.
      Artificial release experiments (chemical and electrical) and electrophysiological
      measurements were conducted with two phylogenetically distant species, Goeppertia
      bachemiana (E. Morren) Borchs. & S. Suarez and Donax canniformis (G. Forst.) K.
      Schum. Electric responses recorded after style release by extracellular
      measurements are characterised as variation potentials due to their long
      repolarization phase and lack of self-perpetuation. In both species, chemical and
      electric stimulations do not release the style movement. It is concluded that the
      style movement in Marantaceae is released mechanically by relieving the tissue
      pressure. Accordingly, the variation potential is an effect of the movement and
      not its cause. The study exemplarily shows that fast movements in plants are not
      necessarily initiated by electric changes of the membrane as known from the Venus
      flytrap. 

PMID- 25997014
TI  - Defining and predicting short-term alcohol use changes during a smoking cessation
      attempt.
AB  - INTRODUCTION: Alcohol and nicotine are commonly used substances in the U.S., with
      significant impacts on health. Using both substances concurrently impacts quit
      attempts. While studies have sought to examine changes in alcohol use co
      occurring with tobacco cessation, results have not been consistent. Understanding
      these changes has clinical implications. The objective of this study is to
      identify changes in alcohol consumption that occur following tobacco cessation,
      as well as predictors of alcohol use patterns following a smoking cessation
      attempt. METHODS: A secondary analysis of a randomized, placebo-controlled trial
      evaluating the efficacy of five tobacco cessation pharmacotherapies. Participants
      (N=1301) reported their smoking and alcohol consumption daily for two weeks prior
      to, and two weeks after, the target quit date (TQD). RESULTS: Generally, alcohol
      use decreased post-TQD. Smokers who reported less pre-quit alcohol use, as well
      as smokers who were female, non-white, and had a history of alcohol dependence
      tended to use less alcohol post-quit. Pre- and post-quit alcohol use were more
      strongly related among men and among those without a history of alcohol
      dependence. CONCLUSIONS: For most smokers alcohol use decreased following smoking
      cessation. These results suggest that the expectation should be of decreased
      alcohol use post cessation. However, attention may be warranted for those who
      drink higher amounts of alcohol pre-cessation because they may be more likely to
      drink more in the post-quit period which may influence smoking cessation success.

PMID- 25997016
TI  - Long-term Results of Observation vs Prophylactic Selective Level VI Neck
      Dissection for Papillary Thyroid Carcinoma at a Cancer Center.
AB  - IMPORTANCE: The indication for prophylactic central neck dissection in papillary
      thyroid cancer (PTC) is controversial. OBJECTIVE: To compare long-term results of
      observation vs prophylactic selective level VI neck dissection for PTC. DESIGN,
      SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of 812
      patients with PTC who were treated from January 1, 1996, through January 1, 2007,
      at the Department of Head and Neck Surgery and Otorhinolaryngology of A. C.
      Camargo Cancer Center. A group of 580 consecutive patients with previously
      untreated PTCs and without lymph node metastasis were eligible for the study. We
      collected and analyzed retrospective data from February 1, 2012, through August
      31, 2013. INTERVENTIONS: One hundred two patients (group A) underwent total
      thyroidectomy with elective central neck dissection; 478 patients (group B)
      underwent total thyroidectomy alone. MAIN OUTCOMES AND MEASURES: Absence of
      difference in rates of locoregional control and rates of major complications in
      group A. RESULTS: In group A, the rate of occult metastatic disease was 67.2%.
      Patients in group A exhibited higher rates of temporary hypocalcemia (46.1% vs
      32.2%; P = .004) and permanent hypoparathyroidism (11.8% vs 2.3%; P < .001). We
      also found a significantly higher incidence of temporary (11.8% vs 6.1%; P = .04)
      and permanent (5.9% vs 1.5%; P = .02) recurrent laryngeal nerve dysfunction in
      group A. The overall recurrence rate at level VI was 1.9%. CONCLUSIONS AND
      RELEVANCE: Although the risk for occult lymph node metastasis reached 67.2% in a
      selected group of patients, elective central neck dissection for patients with
      PTC increased the risk for complications and did not contribute to a decrease in
      local recurrence rates.

PMID- 25997017
TI  - GLS2 is transcriptionally regulated by p73 and contributes to neuronal
      differentiation.

PMID- 25997020
TI  - Identification of Anti-EGFR and Anti-ErbB3 Dual Variable Domains Immunoglobulin
      (DVD-Ig) Proteins with Unique Activities.
AB  - Epidermal growth factor receptor (EGFR) and receptor tyrosine-protein kinase 3
      (ErbB3) are two well-established targets in cancer therapy. There is significant
      crosstalk among these two receptors and others. To block signaling from both EGFR
      and ErbB3, we generated anti-EGFR and anti-ErbB3 DVD-Ig proteins. Two DVD-Ig
      proteins maintained the functions of the combination of the two parental
      antibodies. The DVD-Ig proteins inhibit cell signaling and proliferation in A431
      and FaDu cells while half DVD-Ig proteins lost proliferation inhibition function.
      Interestingly, in the presence of beta-Heregulin (HRG), the DVD-Ig proteins show
      synergies with respect to inhibiting cell proliferation. The DVD-Ig proteins
      downregulate EGFR protein expression in the presence of HRG, which may be due to
      receptor internalization. Furthermore, the DVD-Ig proteins remarkably disrupt
      beta-Heregulin binding to FaDu cells. 

PMID- 25997021
TI  - Effect of dexmedetomidine on preventing postoperative agitation in children: a
      meta-analysis.
AB  - BACKGROUND: Emergence agitation (EA) is one of the most common postoperative
      complications in children. The purpose of this meta-analysis is to assess the
      effect of dexmedetomidine for preventing postoperative agitation in children.
      METHODS: We searched the Cochrane Central Register of Controlled Trails, MEDLINE,
      and EMBASE. Randomized controlled trials were included. The following outcome
      measures were evaluated: incidence of EA, number of patients requiring rescue,
      time to eye-open, time to extubation, time to discharge from the postanesthesia
      care unit (PACU). RESULTS: We analyzed 19 trials (1608 patients) that met the
      inclusion criteria. Compared with placebo, intravenous dexmedetomidine
      significantly reduced the incidence of EA [risk ratio (RR) 0.34, 95% confidence
      interval (CI) 0.25-0.44, P<0.00001). Dexmedetomidine also decreased the incidence
      of severe pain (RR 0.41, 95% CI 0.27-0.62, P<0.0001) and requirement of a rescue
      drug (RR 0.31, 95% CI 0.18-0.53, P<0.0001). However, compared with placebo,
      dexmedetomidine increased the time to eye-open by 0.98 min (P = 0.01) and the
      time to PACU discharge by 4.63 min (P = 0.02). Dexmedetomidine was also compared
      with midazolam, propofol, ketamine, and fentanyl, among others. No significant
      difference was found in the incidence of EA for most of these comparisons, with
      the exception of fentanyl and propofol, where dexmedetomidine was more
      beneficial. CONCLUSIONS: Dexmedetomidine was proved effective for preventing EA
      and for reducing severe pain and the requirement of rescue drugs. It slightly
      increased the time to eye-open and the time to PACU discharge. Dexmedetomidine
      was also more beneficial than propofol or fentanyl in preventing EA.

PMID- 25997023
TI  - Eosinophil-rich syphilis: a report of four cases.
AB  - The differential diagnosis for eosinophil-rich skin lesions often includes a drug
      reaction, allergic contact dermatitis and rarely, response to a helminth
      infection. However, many unrelated entities, such as infections, neoplasms and
      inflammatory dermatoses, can have a prominent eosinophilic infiltrate. Syphilis
      is classically associated with plasma cells, but other patterns of inflammation
      have been reported, including ulcerative, granulomatous and eosinophil-rich.
      Classic teaching might indicate that the presence of eosinophils argues against a
      diagnosis of syphilis. We present four cases of secondary syphilis with increased
      eosinophils, ranging from 8 to >200 eosinophils per 10 high-power fields (*400
      magnification). Patient 1 had lesions on the penis and scrotum, with greater than
      200 eosinophils per 10 high-power fields. Patient 2 had lesions on the back, with
      150 eosinophils per 10 high-power fields. Patient 3 had lesions on the bilateral
      arms, with 8 eosinophils per 10 high-power fields. Patient 4 had lesions
      involving the anus, with 17 eosinophils per 10 high-power fields. These cases
      highlight that the presence of an eosinophil-rich infiltrate on skin biopsy
      should not exclude syphilis from the differential diagnosis. 

PMID- 25997024
TI  - Ring-opening polymerization of rac-lactide and alpha-methyltrimethylene carbonate
      catalyzed by magnesium and zinc complexes derived from binaphthyl-based
      iminophenolate ligands.
AB  - A series of racemic 2-[(2'-(dimethylamino)binaphthyl-2-ylimino)methyl]-4-R2-6
      R(1)-phenols (L1H-L6H) were reacted with 1 equiv. of Mg[N(SiMe3)2]2 or
      Zn[N(SiMe3)2]2 to provide three heteroleptic magnesium silylamido complexes [(L4
      (6))MgN(SiMe3)2] (4a: R(1) = R(2) = cumyl; 5a: R(1) = CPh3, R(2) = Me; 6a: R(1) =
      CPh3, R(2) = (t)Bu) and one heteroleptic zinc silylamido complex
      [(L(4))ZnN(SiMe3)2] (4b: R(1) = R(2) = cumyl). The molecular structures of
      complexes 4a, 4b and a homolepic zinc complex (L(5))2Zn (5b') were further
      confirmed by X-ray diffraction studies. In the solid state, the heteroleptic
      magnesium complex 4a has a four-coordinated metal core chelated by three donor
      atoms of the ligand and one bis(trimethylsilyl)amido group; however, the
      heteroleptic zinc complex 4b has a three-coordinated metal core chelated by two
      donor atoms of the ligand and one bis(trimethylsilyl)amido group, where the NMe2
      group of the iminophenolate ligand is not coordinated to the zinc center.
      Magnesium complexes 4a-6a efficiently initiated the ring-opening polymerization
      (ROP) of rac-lactide in the presence/absence of 2-propanol, affording atactic
      polylactides in toluene and heterotactic bias polylactides in THF. Zinc complex
      4b exhibited the highest stereoselectivity for the ROP of rac-lactide, affording
      substantially heterotactic polylactides in both solvents (Pr = 0.80-0.84). The
      kinetic studies of the polymerization revealed that the rate of polymerization is
      first-order in both monomer and catalyst concentrations. All these complexes were
      also very active in the polymerization of racemic alpha-methyltrimethylene
      carbonate (alpha-MeTMC). Detailed analyses using 1H and 13C NMR spectroscopy
      indicated the preferential ring-opening of alpha-MeTMC at the most hindered
      oxygen-acyl bond and zinc complex 4b gave the highest regioselectivity (Xreg =
      0.98).

PMID- 25997025
TI  - Reliable Attention Network Scores and Mutually Inhibited Inter-network
      Relationships Revealed by Mixed Design and Non-orthogonal Method.
AB  - The attention system can be divided into alerting, orienting, and executive
      control networks. The efficiency and independence of attention networks have been
      widely tested with the attention network test (ANT) and its revised versions.
      However, many studies have failed to find effects of attention network scores
      (ANSs) and inter-network relationships (INRs). Moreover, the low reliability of
      ANSs can not meet the demands of theoretical and empirical investigations. Two
      methodological factors (the inter-trial influence in the event-related design and
      the inter-network interference in orthogonal contrast) may be responsible for the
      unreliability of ANT. In this study, we combined the mixed design and non
      orthogonal method to explore ANSs and directional INRs. With a small number of
      trials, we obtained reliable and independent ANSs (split-half reliability of
      alerting: 0.684; orienting: 0.588; and executive control: 0.616), suggesting an
      individual and specific attention system. Furthermore, mutual inhibition was
      observed when two networks were operated simultaneously, indicating a
      differentiated but integrated attention system. Overall, the reliable and
      individual specific ANSs and mutually inhibited INRs provide novel insight into
      the understanding of the developmental, physiological and pathological mechanisms
      of attention networks, and can benefit future experimental and clinical
      investigations of attention using ANT. 

PMID- 25997026
TI  - Climate and socioeconomic influences on interannual variability of cholera in
      Nigeria.
AB  - Cholera is one of the most important climate sensitive diseases in Nigeria that
      pose a threat to public health because of its fatality and endemic nature. This
      study aims to investigate the influences of meteorological and socioeconomic
      factors on the spatiotemporal variability of cholera morbidity and mortality in
      Nigeria. Stepwise multiple regression and generalised additive models were fitted
      for individual states as well as for three groups of the states based on annual
      precipitation. Different meteorological variables were analysed, taking into
      account socioeconomic factors that are potentially enhancing vulnerability (e.g.
      absolute poverty, adult literacy, access to pipe borne water). Results quantify
      the influence of both climate and socioeconomic variables in explaining the
      spatial and temporal variability of the disease incidence and mortality. Regional
      importance of different factors is revealed, which will allow further insight
      into the disease dynamics. Additionally, cross validated models suggest a strong
      possibility of disease prediction, which will help authorities to put effective
      control measures in place which depend on prevention, and or efficient response. 

PMID- 25997028
TI  - Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy.

PMID- 25997029
TI  - Differential Myocyte Responses in Patients with Cardiac Transthyretin Amyloidosis
      and Light-Chain Amyloidosis: A Cardiac MR Imaging Study.
AB  - PURPOSE: To investigate cardiac magnetic resonance (MR) imaging measurements of
      extracellular volume (ECV) and total cell volume in immunoglobulin light-chain
      amyloidosis (AL) and transthyretin amyloidosis (ATTR) in order to evaluate the
      amyloid and myocyte volumes. MATERIALS AND METHODS: All ethics were approved, and
      participants provided written informed consent. Of the 257 subjects who were
      recruited, 92 had AL (mean age, 62 years +/- 10), 44 had mutant ATTR (mean age,
      68 years +/- 10), and 66 had wild-type ATTR (mean age, 75 years +/- 7). In
      addition, eight healthy subjects with ATTR mutations (mean age, 47 years +/- 6)
      and 47 healthy volunteers (mean age, 45 years +/- 15) participated. All
      participants underwent equilibrium contrast material-enhanced cardiac MR imaging.
      ECV and total cell volume were measured in the heart. T test, chi(2), and one-way
      analysis of variance with posthoc Bonferroni correction were used. RESULTS: Both
      the left ventricular indexed mass and ECV were elevated in patients with
      amyloidosis. For left ventricular indexed mass, mean AL was 107 g/m(2) +/- 30;
      mean mutant ATTR was 137 g/m(2) +/- 29; and mean wild-type ATTR was 133 g/m(2) +/
      27 versus 65 g/m(2) +/- 15 in healthy subjects (P < .0001 for all measures). For
      ECV, mean AL was 0.54 +/- 0.07, mean mutant ATTR was 0.60 +/- 0.07, and mean wild
      type ATTR was 0.57 +/- 0.06 versus 0.27 +/- 0.03 in healthy subjects (P < .0001
      for all measures). Patients with ATTR had a higher total cell volume than did
      healthy subjects (mean, 53 mL/m(2) +/- 12 vs 45 mL/m(2) +/- 11; P = .001), but in
      patients with AL, total cell volume was normal (mean, 47 mL/m(2) +/- 17 vs 45
      mL/m(2) +/- 11; P > .99). The result is that, in patients with AL, all of the
      increase in left ventricular indexed mass is extracellular volume, whereas in
      patients with ATTR, the increase is extracellular, with an additional 18%
      increase in the intracellular space. CONCLUSION: Quantification of ECV measures
      cardiac amyloid deposition in both types of amyloidosis and shows that amyloid
      deposition is more extensive in patients with ATTR than in those with AL;
      however, ATTR is associated with higher cell volume, which suggests concomitant
      cell hypertrophy.

PMID- 25997030
TI  - Label-free Detection of Lymph Node Metastases with US-guided Functional
      Photoacoustic Imaging.
AB  - PURPOSE: To determine the ability of ultrasonography (US)-guided spectroscopic
      photoacoustic (sPA) imaging to depict changes in blood oxygen saturation (SO2) in
      metastatic lymph nodes of a mouse model of oral cancer. MATERIALS AND METHODS:
      All studies were performed by following protocols approved by the institutional
      animal care and use committee at the University of Texas at Austin. Coregistered
      US and photoacoustic images were acquired spanning volumes containing a total of
      31 lymph nodes in 17 female nu/nu mice. The mice were either healthy (three mice,
      five nodes) or bearing a primary tumor consisting of luciferase-labeled FaDu
      cells (14 mice, 26 nodes). Ten photoacoustic images acquired with optical
      wavelengths spanning from 680 to 860 nm were spectrally unmixed by using a linear
      least-squares method to obtain sPA images. After imaging, histologic analysis
      enabled confirmation of the presence of micrometastases. Generalized estimating
      equations were used to compare metastatic and normal lymph nodes, with a P value
      of .05 taken to indicate a significant difference. Sensitivity and specificity
      were determined with a receiver operator characteristic curve constructed from
      the background-subtracted SO2 values. RESULTS: Metastatic lymph nodes (n = 7)
      exhibited a significantly (P = .018) lower spatially averaged background
      subtracted SO2 (mean, 5.4% +/- 3.5 [standard error]) when compared with lymph
      nodes without metastases (mean, 13.7% +/- 1.3; n = 24). This effect was observed
      throughout the entire volume of the nodes rather than being limited to the
      metastatic foci. The change in SO2, which was inversely related to the size of
      the metastasis, was detectable in metastases as small as 2.6 * 10(-3) mm(3).
      CONCLUSION: The results show that US-guided sPA imaging is capable of depicting
      changes in SO2 in lymph nodes that were correlated with metastatic invasion.

PMID- 25997031
TI  - Unresectable Adrenal Metastases: Clinical Outcomes of Radiofrequency Ablation.
AB  - PURPOSE: To retrospectively evaluate the clinical outcomes of radiofrequency (RF)
      ablation for the treatment of unresectable adrenal metastasis. MATERIALS AND
      METHODS: The institutional review board approved this retrospective study, and
      informed consent to perform adrenal RF ablation was obtained from all patients.
      From February 2005 through May 2014, 35 patients (25 men and 10 women; mean age,
      64.7 years +/- 9.6; age range, 39-82 years) underwent RF ablation to treat 41
      metastatic adrenal tumors from lung cancer (n = 15), renal cell carcinoma (n =
      9), colorectal cancer (n = 5), hepatocellular carcinoma (n = 4), and other tumors
      (n = 2). Tumors ranged in size from 1.2 to 8.2 cm (mean, 3.3 cm +/- 1.6). The
      diagnosis was established mainly on the basis of radiologic findings. Adrenal
      arterial embolization was combined with RF ablation in 12 of the 35 patients
      (34%). Technical success, safety, local tumor progression, and survival were
      evaluated. The Kaplan-Meier method and Cox proportional hazard model were used to
      evaluate prognostic factors. RESULTS: There were 48 completed sessions with
      planned procedures and treatment protocols with no mortality and a major
      complication rate of 8.3% (four of 48 sessions). Tumor enhancement disappeared
      after initial adrenal RF ablation in 33 of the 35 patients (94%). Local tumor
      progression developed in eight of the 35 patients (23%); two patients received
      repeated RF ablation, resulting in adrenal tumor control in 27 of the 35 patients
      (77%) at the last follow-up (mean, 30.1 months +/- 27.5; range 1.2-96.8 months).
      The 1-, 3-, and 5-year overall survival rates were 75% (95% confidence interval
      [CI], 61%, 90%), 34% (95% CI: 17%, 52%), and 30% (95% CI: 13%, 48%),
      respectively, with a median survival time of 26.0 months. Existence of extra
      adrenal tumors (P = .005) and age of 65 years or older (P = .04) were significant
      indicators of a poor prognosis. CONCLUSION: Adrenal RF ablation is a feasible and
      useful method for controlling adrenal metastases and offers patients
      opportunities for improved survival.

PMID- 25997032
TI  - Designing the furin-cleavable linker in recombinant immunotoxins based on
      Pseudomonas exotoxin A.
AB  - Recombinant immunotoxins (RITs) are fusion proteins that join antibodies to
      protein toxins for targeted cell killing. RITs armed with Pseudomonas exotoxin A
      (PE) are undergoing clinical trials for the treatment of cancer. The current
      design of PE-based RITs joins an antibody fragment to the catalytic domain of PE
      using a polypeptide linker that is cleaved by the protease furin. Intracellular
      cleavage of native PE by furin is required for cytotoxicity, yet the PE cleavage
      site has been shown to be a poor furin substrate. Here we describe the rational
      design of more efficiently cleaved furin linkers in PE-based RITs, and
      experiments evaluating their effects on cleavage and cytotoxicity. We found that
      changes to the furin site could greatly influence both cleavage and cytotoxicity,
      but the two parameters were not directly correlated. Furthermore, the effects of
      alterations to the furin linker were not universal. Identical mutations in the
      anti-CD22 RIT HA22-LR often displayed different cytotoxicity from mutations in
      the anti-mesothelin RIT SS1-LR/GGS, underscoring the prominent role of the target
      site in their intoxication pathways. Combining several beneficial mutations in
      HA22-LR resulted in a variant (HA22-LR/FUR) with a remarkably enhanced cleavage
      rate and improved cytotoxicity against five B cell lines and similar or enhanced
      cytotoxicity in five out of six hairy cell leukemia patient samples. This result
      informs the design of protease-sensitive linkers and suggests that HA22-LR/FUR
      may be a candidate for further preclinical development. 

PMID- 25997034
TI  - Intravenous immunoglobulin in the treatment of neurologic disorders.
AB  - Intravenous immunoglobulins (IVIGs) are often used in the treatment of autoimmune
      disorders and immunodeficiencies, and it has been estimated that neurologic
      indications can account for up to 43% of IVIG used in clinical practice. In
      neurologic clinical practice, IVIG is used for acute therapy of newly diagnosed
      autoimmune disorders or exacerbations of pre-existing conditions, or as long-term
      maintenance treatment for chronic disorders. IVIG exerts its effects on humoral
      and cell-based immunity through multiple pathways, without a single dominant
      mechanism. Clinical use of IVIG has been supported by guidelines from American
      Academy of Neurology and European Federation of Neurologic Societies. IVIG is
      generally recommended for the treatment of Guillain-Barre syndrome and chronic
      inflammatory demyelinating polyneuropathy in adults, multifocal motor neuropathy
      and myasthenia gravis, and should be considered as a treatment option for
      dermatomyositis in adults and Lambert-Eaton myasthenic syndrome. Additional
      potential indications include stiff person syndrome, multiple sclerosis during
      pregnancy or while breastfeeding, refractory autoimmune epilepsy, and
      paraneoplastic disorders. Clinical use of IVIG is mostly safe but few adverse
      effects may still occur with potentially severe complications, including aseptic
      meningitis and thromboembolism. In addition to intravenous route (IVIG),
      subcutaneous immunoglobulins have been used as an alternative treatment option,
      especially in patients with limited intravenous access. Treatment with IVIG is
      effective in various autoimmune diseases, but its broader use is constrained by
      limited supply. This review evaluates the use of immunoglobulins in treatment of
      neurologic diseases.

PMID- 25997033
TI  - Identification of a novel cellular target and a co-factor for norovirus infection
      - B cells & commensal bacteria.
AB  - Human noroviruses are a leading cause of gastroenteritis worldwide but research
      on these important enteric pathogens has long been restricted by their
      uncultivability. Extensive efforts to infect intestinal epithelial cells with
      murine and human noroviruses in vitro have been thus far unsuccessful while
      murine noroviruses efficiently and lytically infect innate immune cells including
      macrophages and dendritic cells. We have recently discovered that murine and
      human noroviruses infect B cells in vitro. The nature of B cell infection was
      distinct from innate immune cell infection in that mature B cells were infected
      noncytopathically in contrast to the lytic infection of macrophages and dendritic
      cells. Human norovirus infection of B cells was facilitated by commensal bacteria
      expressing an appropriate histo-blood group antigen. Importantly, we used the
      mouse model of norovirus infection to confirm that Peyer's patch B cells are
      infected, and that commensal bacteria stimulate infection, in vivo. 

PMID- 25997035
TI  - In antisynthetase syndrome, ACPA are associated with severe and erosive
      arthritis: an overlapping rheumatoid arthritis and antisynthetase syndrome.
AB  - Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific
      for rheumatoid arthritis (RA), may be found in some patients with other systemic
      autoimmune diseases. The clinical significance of ACPA in patients with
      antisynthetase syndrome (ASS), a systemic disease characterized by the
      association of myositis, interstitial lung disease, polyarthralgia, and/or
      polyarthritis, has not yet been evaluated with regard to phenotype, prognosis,
      and response to treatment. ACPA-positive ASS patients were first identified among
      a French multicenter registry of patients with ASS. Additionally, all French
      rheumatology and internal medicine practitioners registered on the Club
      Rhumatismes et Inflammation web site were asked to report their observations of
      ASS patients with ACPA. The 17 collected patients were retrospectively studied
      using a standardized questionnaire and compared with 34 unselected ACPA-negative
      ASS patients in a case-control study. All ACPA-positive ASS patients suffered
      from arthritis versus 41% in the control group (P < 0.0001). The number of
      swollen joints was significantly higher (7.0 +/- 5.0 vs 2.9 +/- 3.9, P < 0.005),
      with a distribution resembling that of RA. Radiographic damages were also more
      frequent in ACPA-positive ASS patients (87% vs 11%, P < 0.0001). Aside from a
      significantly higher transfer factor for carbon monoxide in ACPA-ASS patients,
      lung, muscle, and skin involvements had similar incidences, patterns, and
      severity in both groups. Although Nonbiologic treatments were similarly used in
      both groups, ACPA-positive patients received biologics more frequently (59% vs
      12%, P < 0.0008), mostly due to refractory arthritis (n = 9). Eight patients
      received anti-Cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs)
      with good efficacy and tolerance, whereas 2 of the 5 patients treated with
      antitumor necrosis factor drugs had worsened myositis and/or interstitial lung
      disease. After a >7-year mean follow-up, extra-articular outcomes and survival
      were not different. ACPA-positive ASS patients showed an overlapping RA-ASS
      syndrome, were at high risk of refractory erosive arthritis, and might experience
      ASS flare when treated with antitumor necrosis factor drugs. In contrast, other
      biologics such as anti-CD20 mAb were effective in this context, without worsening
      systemic involvements.

PMID- 25997036
TI  - An intriguing case report of functional mitral regurgitation treated with
      MitraClip.
AB  - Functional mitral regurgitation (FMR) is frequent in patients with heart failure
      (HF). It develops as a consequence of left ventricle (LV) geometry alterations,
      causing imbalance between increased tethering forces and decreased closing forces
      exerted on the mitral valve apparatus during systole.FMR is known to change at
      rest and during effort, due to preload-afterload changes, myocardial ischemia,
      and/or LV dysfunction. Despite optimized medical therapy, an FMR can be
      responsible of shortness of breath limiting quality of life and decompensation.
      In this report, we present a case of dynamic FMR treated with MitraClip.MitraClip
      implantation is a successful and innovative opportunity for HF patients with FMR.

PMID- 25997037
TI  - Hepatic, renal and inflammatory biomarkers are positively associated with blood
      pressure changes in healthy pregnant women: a prospective cohort.
AB  - This article evaluates the association of hepatic, renal, and inflammatory
      biomarkers with changes in systolic (SBP) and diastolic (DBP) blood pressure (BP)
      during healthy pregnancies.A prospective cohort study with 225 healthy pregnant
      women was conducted in Rio de Janeiro, Brazil. SBP and DBP were evaluated
      throughout pregnancy (5th-13th, 20th-26th, and 30th-36th gestational weeks) and
      were the outcomes. The following biomarkers were measured at the first trimester
      and analyzed according to tertiles of the sample distribution and were considered
      the main independent predictors: alkaline phosphatase (ALP), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA),
      creatinine (Cr), and C-reactive protein (CRP) concentrations. The statistical
      analysis included 3 stages of modeling with the longitudinal linear mixed-effects
      procedures: Model 1 was adjusted for gestational age and quadratic gestational
      age; Model 2 included interactions between the biomarkers and gestational age;
      and Model 3 was adjusted for self-reported skin color, education, parity, early
      pregnancy body mass index (BMI) (under/normal <25; overweight/obese >=25 kg/m),
      smoking habit, and leisure-time physical activity. Additional models were
      performed for CRP and UA with the inclusion of interaction terms between the
      biomarkers and BMI.Women classified in the third tertile of the ALP (>=61.1 U/L;
      betaSBP = 3.474; 95% confidence interval [CI]: 0.955-5.992; betaDBP = 3.291; 95%
      CI: 1.098-5.485), ALT (>=14.3 U/L; betaSBP = 2.232; 95% CI: 0.221-4.242; betaDBP
      = 2.355; 95% CI: 0.721-3.989), and Cr values (>=48.6 MUmol/L; betaDBP = 1.927;
      95% CI: 0.347-3.508) presented higher BP levels during pregnancy compared to
      those in the first and second tertiles. Women in the highest tertile of the ALP
      concentration distribution presented a lower rate of change in SBP and DBP during
      pregnancy (interaction term with gestational age betaSBP = -0.004; 95% CI: -0.007
      to -0.001; P = 0.02; betaDBP = -0.003; 95% CI: -0.006 to -0.001; P = 0.01).
      Higher UA concentrations were associated with higher SBP levels only in
      overweight/obese women (beta = 3.878; 95% CI: 0.687-7.068), whereas higher CRP
      concentrations (>=2.6 mg/L) were associated with higher DBP in under/normal
      weight women (beta =2.252; 95% CI: 0.267-4.236).ALP, ALT, and Cr concentrations
      were positively associated with BP levels, whereas ALP was associated with a
      lower rate of change in BP. The associations of UA and CRP with BP differ
      according to the early-pregnancy BMI.

PMID- 25997038
TI  - Impact of bariatric surgery on carotid artery inflammation and the metabolic
      activity in different adipose tissues.
AB  - In this study, we unravel a molecular imaging marker correlated with the known
      reduction of cardiovascular events (most commonly related to vulnerable plaques)
      in morbidly obese patients after bariatric surgery (BaS).We prospectively imaged
      10 morbidly obese subjects with F-fluorodeoxyglucose (F-FDG) positron emission
      tomography/computed tomography before and 1 year after BaS. F-FDG uptake-which is
      enhanced in inflamed, atherosclerotic vessels and in metabolically active adipose
      tissues-was quantified in the carotids, pericardial adipose tissue (PAT),
      visceral adipose tissue (VAT), as well as brown adipose tissue (BAT). The degree
      of carotid inflammation was compared to lean and overweight controls.Carotid
      inflammation significantly declined leading to an F-FDG uptake comparable to the
      2 control groups. Metabolic activity significantly decreased in PAT and VAT and
      increased in BAT.BaS leads to a normalization of carotid artery inflammation and
      a beneficial impact on the metabolic activity in PAT, VAT, and BAT that is
      related to the metabolic syndrome observed in this patient group.

PMID- 25997039
TI  - Cadmium status among pediatric cancer patients in Egypt.
AB  - Cadmium (Cd) is a toxic, nonessential, and bio-accumulating heavy metal widely
      used in industry. Several studies have suggested a positive association between
      Cd exposure and risks of several cancers. However, data from general population,
      especially children are sparse.In the current cross-sectional case-control study,
      we aimed to assess the association between Cd exposure, as expressed by Cd body
      status (blood, urine, scalp hair, and nails) and cancer among Egyptian children.
      Three hundred and fifty pediatric cancer cases aged 3 to 14-years old were
      enrolled in our study. Their body Cd levels were evaluated using Atomic
      Absorption Spectrophometer and were compared with Cd levels of 350 healthy
      children.Significantly higher Cd levels (blood, urine, scalp hair, and nails)
      were documented in cancer cases when compared with control (P < 0.001). Such
      difference was still detected when comparing each malignant type separately, with
      controls. Tobacco smoke exposure, rural residence, and low socioeconomic status
      were reported more frequently among cases than comparisons.Positive association
      between Cd exposure and pediatric malignancy may be present.

PMID- 25997040
TI  - Positron emission tomography scanning in anti-neutrophil cytoplasmic antibodies
      associated vasculitis.
AB  - Tools for evaluation of disease activity in patients with anti-neutrophil
      cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) include scoring
      clinical manifestations, determination of biochemical parameters of inflammation,
      and obtaining tissue biopsies. These tools, however, are sometimes inconclusive.
      2-deoxy-2-[F]-fluoro-D-glucose (FDG) positron emission tomography (PET) scans are
      commonly used to detect inflammatory or malignant lesions. Our objective is to
      explore the ability of PET scanning to assess the extent of disease activity in
      patients with AAV.Consecutive PET scans made between December 2006 and March 2014
      in Maastricht (MUMC) and between July 2008 and June 2013 in Brussels (EUH) to
      assess disease activity in patients with AAV were retrospectively included. Scans
      were re-examined and quantitatively scored using maximum standard uptake values
      (SUVmax). PET findings were compared with C-reactive protein (CRP) and ANCA
      positivity at the time of scanning.Forty-four scans were performed in 33 patients
      during a period of suspected active disease. All but 2 scans showed PET-positive
      sites, most commonly the nasopharynx (n = 22) and the lung (n = 22). Forty-one
      clinically occult lesions were found, including the thyroid gland (n = 4
      patients), aorta (n = 8), and bone marrow (n = 7). The amount of hotspots, but
      not the highest observed SUVmax value, was higher if CRP levels were elevated.
      Seventeen follow-up scans were made in 13 patients and showed decreased SUVmax
      values.FDG PET scans in AAV patients with active disease show positive findings
      in multiple sites of the body even when biochemical parameters are inconclusive,
      including sites clinically unsuspected and difficult to assess otherwise.

PMID- 25997041
TI  - Percutaneous embolization for ruptured ectopic bronchial artery aneurysm: a case
      report.
AB  - Bronchial artery aneurysm (BAA) is an uncommon disease, and spontaneous rupture
      of an ectopic BAA can be difficult for diagnosis and life-threatening. This case
      study describes a 52-year-old man who presented with acute onset of right chest
      pain, mild tachycardia, and hypertension. The initial diagnosis of acute
      myocardial infarction was made, and the patient was given nitroglycerin prior to
      admission to our hospital. However, the patient's symptoms deteriorated. An
      enhanced computed tomography scan revealed a ruptured 25-mm diameter mediastinal
      aneurysm under the tracheal bifurcation when he was admitted to our hospital.
      Bronchial arteriography further demonstrated a ruptured mediastinal BAA of a
      bronchial artery originated from the left subclavian artery, supplying the right
      lobe. Transcatheter artery embolization with polyvinyl alcohol particles and
      microcoils was performed successfully. The patient's symptoms were gradually
      relieved, and without recurrence on 1 year follow-up.This case highlights the
      rare variation of mediastinal BAA and the role of interventional radiology in
      diagnosing and treating this critical condition.

PMID- 25997042
TI  - Intraoperative computed tomography navigation for transpedicular screw fixation
      to treat unstable thoracic and lumbar spine fractures: clinical analysis of a
      case series (CARE-compliant).
AB  - Transpedicular screw (TPS) fixation in unstable thoracic and lumbar (TL) spine
      fractures remains technically difficult because of destroyed anatomical
      landmarks, unstable gross segments, and discrepancies in anatomic orientation
      using conventional anatomic landmarks, fluoroscopic guidance, or computed
      tomography (CT)-based navigation. In this study, we evaluated the safety and
      accuracy of TPS placement under intraoperative computed tomography (iCT)
      navigation in managing unstable TL spine fractures.From 2010 to 2013, we
      retrospectively reviewed the Spine Operation Registry records of patients who
      underwent posterior instrumented fusion to treat unstable TL spine fractures via
      the iCT navigation system. An unstable spine fracture was identified as AO/Magerl
      classification type B or type C.In all, 316 screws in 37 patients with unstable
      TL spine fractures were evaluated and involved 7 thoracic, 23 thoracolumbar
      junctional, and 7 lumbar fractures. The accuracy of TPS positioning in the
      pedicle without breach was 98% (310/316). The average number of iCT scans per
      patient was 2.1 (range 2-3). The average total radiation dose to patients was
      15.8 mSv; the dose per single level exposure was 2.7 mSv. The TPS intraoperative
      revision rate was 0.6% (2/316) and no neurovascular sequela was observed. TPS
      fixation using the iCT navigation system obtained a 98% accuracy in stabilizing
      unstable TL spine fractures. A malplaced TPS could be revised during real-time
      confirmation of the TPS position, and no secondary operation was required to
      revise malplaced screws.The iCT navigation system provides accurate and safe
      management of unstable TL spine fractures. In addition, operating room personnel,
      including surgeons and nurses, did not need to wear heavy lead aprons as they
      were not exposed to radiation.

PMID- 25997043
TI  - A CONSORT-compliant, randomized, double-blind, placebo-controlled pilot trial of
      purified anthocyanin in patients with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can
      progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid
      family, has been shown to ameliorate NAFLD-associated pathologies in rodents.The
      aim of this CONSORT-compliant pilot study is to evaluate the effects of
      anthocyanin supplementation on insulin resistance and liver injury biomarkers in
      patients with NAFLD.A total of 74 subjects with NAFLD were divided into 2 groups
      in this double-blind, randomized study. Patients received either purified
      anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12
      weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and
      a set of biomarkers related to NAFLD were evaluated before and after
      intervention.No significant differences were observed in nutrient intake,
      physical activity, anthropometric parameters, or plasma lipid profile between
      patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin
      group exhibited significant decreases (P < 0.05, all comparisons) in plasma
      alanine aminotransferase (-19.1% vs 3.1%), cytokeratin-18 M30 fragment (-8.8% vs
      5.6%) and myeloperoxidase (-75.0% vs -44.8%). Significant decreases from baseline
      in fasting blood glucose and homeostasis model assessment for insulin resistance
      were observed in the anthocyanin group; however, these differences were not
      significant relative to placebo controls. In addition, the oral glucose tolerance
      test indicated that anthocyanin supplementation significantly decreased the 2
      hour loading glucose level compared to control (-18.7% vs -3.8%, P = 0.02).A 12
      week supplement of purified anthocyanin improved insulin resistance, indicators
      of liver injury, and clinical evolution in NAFLD patients. Further studies are
      warranted to determine the clinical applications of anthocyanin in NAFLD.This
      trial was registered at clinicaltrials.gov as NCT01940263.

PMID- 25997044
TI  - Virtual reality training versus blended learning of laparoscopic cholecystectomy:
      a randomized controlled trial with laparoscopic novices.
AB  - This study compared virtual reality (VR) training with low cost-blended learning
      (BL) in a structured training program.Training of laparoscopic skills outside the
      operating room is mandatory to reduce operative times and risks.Laparoscopy-naive
      medical students were randomized in 2 groups stratified for sex. The BL group (n
      = 42) used E-learning for laparoscopic cholecystectomy (LC) and practiced basic
      skills with box trainers. The VR group (n = 42) trained basic skills and LC on
      the LAP Mentor II (Simbionix, Cleveland, OH). Each group trained 3 * 4 hours
      followed by a knowledge test concerning LC. Blinded raters assessed the operative
      performance of cadaveric porcine LC using the Objective Structured Assessment of
      Technical Skills (OSATS). The LC was discontinued when it was not completed
      within 80 min. Students evaluated their training modality with questionnaires.The
      VR group completed the LC significantly faster and more often within 80 min than
      BL (45% v 21%, P = .02). The BL group scored higher than the VR group in the
      knowledge test (13.3 +/- 1.3 vs 11.0 +/- 1.7, P < 0.001). Both groups showed
      equal operative performance of LC in the OSATS score (49.4 +/- 10.5 vs 49.7 +/-
      12.0, P = 0.90). Students generally liked training and felt well prepared for
      assisting in laparoscopic surgery. The efficiency of the training was judged
      higher by the VR group than by the BL group.VR and BL can both be applied for
      training the basics of LC. Multimodality training programs should be developed
      that combine the advantages of both approaches.

PMID- 25997045
TI  - Septal and anterior reverse mismatch of myocardial perfusion and metabolism in
      patients with coronary artery disease and left bundle branch block.
AB  - The effects of left bundle branch block (LBBB) on left ventricular myocardial
      metabolism have not been well investigated. This study evaluated these effects in
      patients with coronary artery disease (CAD).Sixty-five CAD patients with complete
      LBBB (mean age, 61.8 +/- 9.7 years) and 65 without LBBB (mean age, 59.9 +/- 8.4
      years) underwent single photon emission computed tomography, positron emission
      tomography, and contrast coronary angiography. The relationship between
      myocardial perfusion and metabolism and reverse mismatch score, and that between
      QRS length and reverse mismatch score and wall motion score were evaluated.The
      incidence of left ventricular septum and anterior wall reverse mismatching
      between the two groups was significantly different (P < 0.001 and P = 0.002,
      respectively). The incidences of normal myocardial perfusion and metabolism in
      the left ventricular lateral and inferior walls were also significantly different
      between the two groups (P < 0.001 and P < 0.001, respectively). The incidence of
      septal reverse mismatching in patients with mild to moderate perfusion was
      significantly higher among those with LBBB than among those without LBBB (P <
      0.001). In CAD patients with LBBB, septal reverse mismatching was significantly
      more common among those with mild to moderate perfusion than among those with
      severe perfusion defects (P = 0.002). The correlation between the septal reverse
      mismatch score and QRS length was significant (P = 0.026).In patients with CAD
      and LBBB, septal and anterior reverse mismatching of myocardial perfusion and
      metabolism was frequently present; the septal reverse mismatch score negatively
      correlated with the QRS interval.

PMID- 25997046
TI  - Adenovirus pneumonia complicated with acute respiratory distress syndrome: a case
      report.
AB  - Severe adenovirus infection in children can manifest with acute respiratory
      distress syndrome (ARDS) and respiratory failure, leading to the need for
      prolonged mechanical support in the form of either mechanical ventilation or
      extracorporeal life support. Early extracorporeal membrane oxygenation (ECMO)
      intervention for children with ARDS should be considered if selection criteria
      fulfill.We report on a 9-month-old boy who had adenovirus pneumonia with rapid
      progression to ARDS. Real-time polymerase chain reaction tests of sputum and
      pleural effusion samples confirmed adenovirus serotype 7. Chest x-rays showed
      progressively increasing infiltrations and pleural effusions in both lung fields
      within 11 days. Because conventional ARDS therapies failed, we initiated ECMO
      with high-frequency oscillatory ventilation (HFOV) for 9 days. Chest x-rays
      showed gradual improvements in lung expansion.This patient was subsequently
      discharged after a hospital stay of 38 days. Post-ECMO and adenovirus sequelae
      were followed in our outpatient department.Adenovirus pneumonia in children can
      manifest with severe pulmonary morbidity and respiratory failure. The unique lung
      recruitment by HFOV can be a useful therapeutic option for severe ARDS patients
      when combined with sufficient lung rest provided by ECMO.

PMID- 25997047
TI  - Prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in
      Fabry disease: a cross-sectional study.
AB  - Fabry disease (FD) is a lysosomal disorder leading to progressive systemic
      involvement, including microvascular damage that leads to neurological and
      cardiovascular disorders. We hypothesize that the latter could be documented at
      an early stage by performing a microcirculation study with nailfold
      capillaroscopy and evaluation of Raynaud phenomenon.The objective was to measure
      the prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities
      in FD.This cross-sectional study included a standardized questionnaire and a
      nailfold capillaroscopy that assessed previously reported patterns in FD
      (dystrophic and giant capillaries, avascular fields, irregular architecture,
      dilatation and density of capillaries, hemorrhage), and was conducted on 32 Fabry
      patients and 39 controls. Capillaroscopic photographs were reviewed by 2
      independent blinded investigators.Twelve Fabry patients (38%) suffered from
      Raynaud phenomenon, 5 were males (ie, 50% of male Fabry patients), compared with
      2 controls (13%) (P < 0.001), of whom none were males (P < 0.001). Raynaud
      phenomenon was concomitant or before the occurrence of pain in the extremities in
      42% of Fabry patients.More ramified capillaries were significantly observed in
      Fabry patients (12/32, 38%) than in controls (5/39, 13%, P = 0.016).Secondary
      Raynaud phenomenon should lead to screening for FD, especially in men. By
      extension, in high-risk populations for FD, the presence of Raynaud phenomenon
      and ramified capillaries should be assessed.

PMID- 25997048
TI  - Simultaneous transplantation of limbal stem cells may reduce recurrences of
      granular dystrophy after corneal transplantation: 2 long-term case reports.
AB  - To present 2 cases with long-term relapse-free intervals only after limbo
      keratoplasty but not after conventional penetrating keratoplasty in granular
      dystrophy.Retrospective review of the patient charts and photographs taken during
      long-term follow-up of 2 cases with granular dystrophy, in which 1 eye received
      penetrating keratoplasty and the fellow eye received penetrating limbo
      keratoplasty.In the first patient, 1 eye showed extensive recurrence of granular
      deposits 17 years after penetrating keratoplasty was performed while in the
      second eye two-thirds of the corneal transplant adjacent to the transplanted
      limbal area remained clear 12 years after the limbo-corneal transplant. In the
      second patient, 1 eye showed no signs of recurrence 5 years after limbo
      keratoplasty, whereas a recurrence of granular corneal deposits occurred 18
      months after surgery in the fellow eye.These cases show that the simultaneous
      transplantation of healthy donor limbus when performing penetrating keratoplasty
      may prolong recurrence in granular corneal dystrophy. Although we were unable to
      prove it on the molecular level, these clinical courses may support the
      hypothesis that a limbal transplant helps prevent a recurrence.

PMID- 25997049
TI  - Epstein-Barr virus infection and gastric cancer: a systematic review.
AB  - Epstein-Barr virus (EBV) infection is found in a subset of gastric cancers.
      Previous reviews have exclusively focused on EBV-encoded small RNA (EBER)
      positivity in gastric cancer tissues, but a comprehensive evaluation of other
      type of studies is lacking.We searched the PubMed database up to September, 2014,
      and performed a systematic review.We considered studies comparing EBV nucleic
      acids positivity in gastric cancer tissue with positivity in either adjacent non
      tumor tissue of cancer patients or non-tumor mucosa from healthy individuals,
      patients with benign gastric diseases, or deceased individuals. We also
      considered studies comparing EBV antibodies in serum from cancer patients and
      healthy controls.Selection of potentially eligible studies and data extraction
      were performed by 2 independent reviewers. Due to the heterogeneity of studies,
      we did not perform formal meta-analysis.Forty-seven studies (8069 cases and 1840
      controls) were identified. EBER positivity determined by in situ hybridization
      (ISH) was significantly higher in cancer tissues (range 5.0%-17.9%) than in
      adjacent mucosa from the same patients or biopsies from all control groups
      (almost 0%). High EBV nuclear antigen-1 (EBNA-1) positivity by PCR was found in
      gastric cancer tissues, but most were not validated by ISH or adjusted for
      inflammatory severity and lymphocyte infiltration. Only 4 studies tested for EBV
      antibodies, with large variation in the seropositivities of different antibodies
      in both cases and controls, and did not find an association between EBV
      seropositivity and gastric cancer.In summary, tissue-based ISH methods strongly
      suggest an association between EBV infection and gastric cancer, but PCR method
      alone is invalid to confirm such association. Very limited evidence from
      serological studies and the lack of novel antibodies warrant further
      investigations to identify potential risk factors of EBV for gastric cancer.

PMID- 25997050
TI  - Should screening for colorectal neoplasm be recommended in patients at high risk
      for coronary heart disease: a cross-sectional study.
AB  - Colorectal neoplasm (CRN) and coronary heart disease (CHD) share common risk
      factors. We aimed to assess the risk for CRN in patients who are at high risk for
      developing CHD determined by measurements, which are independent from the risk
      factors for CRN.This study was conducted on individuals who underwent total
      colonoscopic examination and were without history of CHD. Two-hundred thirty-five
      subjects (82 with CRN and 153 with normal colonoscopic findings) participated in
      the study. Colorectal carcinoma (CRC) was defined as the presence of
      adenocarcinoma. We measured carotid intima media thickness (CIMT), flow-mediated
      dilation (FMD), and calculated Framingham risk score (FRS) for all participants.
      An increased CIMT (>=1.0 mm), a decreased FMD (<10%), and a high FRS (>20%) were
      defined as high risks for developing CHD. The risk and the prevalence of CRN were
      analyzed in relation to the risk for developing CHD.The ratio of the patients
      with overall-CRN and CRC was significantly higher in individuals who are at high
      risk for developing CHD compared with individuals who are at low risk for
      developing CHD by each 3 risk estimation method (P < 0.05 for all). An increased
      CIMT, a decreased FMD, and a high FRS score were significantly associated with
      the high risk for the presence of CRC (odds ratio [OR]: 6.018, OR: 3.699, and OR:
      4.120, respectively). An increased CIMT, a decreased FMD, and an intermediate FRS
      were significantly associated with the risk for the presence of overall-CRN (OR:
      3.607, OR: 1.866 and OR: 2.889, respectively).The risk for CRN increases as the
      risk for developing CHD increases. It can be suggested that screening for CRN can
      be recommended for individuals who are at high risk for developing CHD.

PMID- 25997051
TI  - Overweight increases the risk of malignancy in patients with pancreatic mucinous
      cystic neoplasms.
AB  - Distinguishing between benign and malignant pancreatic cysts remains a clinical
      challenge. The aim of this study was to investigate the influence of body mass
      index (BMI) and preoperative clinical and cyst features, as described by the
      International Consensus Guidelines, on malignancy in patients with pancreatic
      mucinous cystic neoplasms (PMCNs).A retrospective cohort study was performed on
      patients with PMCNs who underwent surgical resection between January 1994 and
      June 2014. Preoperative BMI, clinical demographic data, cystic features, tumor
      markers, and surgical pathology results were analyzed. Predictors of malignancy
      were determined by univariate and multivariate analysis using logistic
      regression.One hundred sixty-four cases of PMCNs, including 106 intraductal
      papillary mucinous neoplasms (IPMNs) and 58 mucinous cystic neoplasms (MCNs),
      were analyzed. On univariate analysis, older age (P = 0.008), male sex (P =
      0.007), high-risk stigmata (P = 0.007), diabetes mellitus (DM; P = 0.008), and
      BMI >25 (P < 0.001) were associated with malignancy. Multivariate analysis found
      that BMI >25 (odds ratio, 3.99; 95% confidence interval: 1.60-10) was an
      independent predictor of malignancy. In subgroup analysis, BMI >25 was an
      independent predictor of malignancy in IPMNs but not in MCNs.Overweight patients
      with IPMNs have a higher risk of malignancy and should be followed closely or
      undergo resection. The operative strategy for PMCNs should consider cyst-related
      and patient-related risk factors.

PMID- 25997052
TI  - Suggestions for lymph node classification of UICC/AJCC staging system: a
      retrospective study based on 1197 nasopharyngeal carcinoma patients treated with
      intensity-modulated radiation therapy.
AB  - This article provides suggestions for N classification of Union for International
      Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of
      nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI)
      in intensity-modulated radiation therapy (IMRT) era.A total of 1197 nonmetastatic
      NPC patients treated with IMRT were enrolled, and all were scanned by MRI at
      nasopharynx and neck before treatment. MRI-based nodal variables including level,
      laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and
      necrosis were analyzed as potential prognostic factors. Modifications of N
      classification were then proposed and verified.Only nodal level and laterality
      were considered to be significant variables affecting the treatment outcome. N
      classification was thus proposed accordingly: N0, no regional lymph node (LN)
      metastasis; N1, retropharyngeal LNs involvement (regardless of laterality),
      and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels
      I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement.
      This proposal showed significant predicting value in multivariate analysis. N3
      patients indicated relatively inferior overall survival (OS) and distant
      metastasis-free survival (DMFS) than N2 patients; however, the difference showed
      no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively),
      and this was considered to be correlated with the small sample sizes of N3
      patients (79 patients, 6.6%).Nodal level and laterality, but not MAD, ECS, and
      necrosis, were considered to be significant predicting factors for NPC. The
      proposed N classification was proved to be powerfully predictive in our cohort;
      however, treatment outcome of the proposed N2 and N3 patients could not differ
      significantly from each other. This insignificance may be because of the small
      sample sizes of N3 patients. Our results are based on a single-center data, to
      develop a new N classification that is universally acceptable; further
      verification by data from multicenter is warranted.

PMID- 25997054
TI  - Left ventricular diastolic dysfunction in peritoneal dialysis: a forgotten risk
      factor.
AB  - Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing
      peritoneal dialysis (PD). We examined the relationship between LVDD, major
      adverse cardiovascular events (MACE), and mortality in PD patients. A total of
      149 patients undergoing PD with preserved left ventricular systolic function were
      included and followed for 3.5 years. LVDD was diagnosed (according to the
      European Society of Cardiology guidelines) by conventional and tissue Doppler
      echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured.
      The location and volume of adipose tissue were assessed by computed tomography
      (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher
      levels of hsCRP, and more visceral and peritoneal fat than controls. The
      relationship between adjusted visceral adipose tissue and LVDD became
      nonsignificant when hsCRP and baseline demographic data were introduced into the
      logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical
      multivariate Cox regression analysis showed that LVDD was one of the most
      powerful determinants of MACE and mortality after adjusting for all confounding
      factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43-3.51, P =
      0.02 and HR: 2.25, 95% CI: 1.45-2.91, P = 0.04, respectively). Systemic
      inflammation (hsCRP) was also significantly associated with MACE and mortality
      (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated
      with systemic inflammation and increased visceral fat in patients undergoing PD.
      LVDD is also a sensitive, independent indicator of future MACE and mortality in
      PD patients.

PMID- 25997053
TI  - Peripheral frequency of CD4+ CD28- cells in acute ischemic stroke: relationship
      with stroke subtype and severity markers.
AB  - CD4+ CD28- T cells also called CD28 null cells have been reported as increased in
      the clinical setting of acute coronary syndrome. Only 2 studies previously
      analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic
      stroke but, to our knowledge, peripheral frequency of CD28 null cells in each
      TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that
      CD4+ cells and, in particular, the CD28 null cell subset could show a different
      degree of peripheral percentage in subjects with acute ischemic stroke in
      relation to clinical subtype and severity of ischemic stroke.The aim of our study
      was to analyze peripheral frequency of CD28 null cells in subjects with acute
      ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their
      relationship with scores of clinical severity of acute ischemic stroke, and their
      predictive role in the diagnosis of acute ischemic stroke and diagnostic
      subtypeWe enrolled 98 consecutive subjects admitted to our recruitment wards with
      a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients
      without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and
      CD28 null cells has been evaluated with a FACS Calibur flow cytometer.Subjects
      with acute ischemic stroke had a significantly higher peripheral frequency of
      CD4+ cells and CD28 null cells compared to control subjects without acute
      ischemic stroke. Subjects with cardioembolic stroke had a significantly higher
      peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with
      other TOAST subtypes. We observed a significant relationship between CD28 null
      cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC
      curve analysis showed that CD28 null cell percentage may be useful to
      differentiate between stroke subtypes.These findings seem suggest a possible role
      for a T-cell component also in acute ischemic stroke clinical setting showing a
      different peripheral frequency of CD28 null cells in relation of each TOAST
      subtype of stroke.

PMID- 25997055
TI  - Association between the presence of iron deficiency anemia and hemoglobin A1c in
      Korean adults: the 2011-2012 Korea National Health and Nutrition Examination
      Survey.
AB  - Few studies have investigated the clinical effect of iron deficiency anemia (IDA)
      on the use of the Hemoglobin A1c (HbA1c) as a screening parameter for diabetes or
      prediabetes. We investigated the association between IDA and HbA1c levels in
      Korean adults.Among the 11,472 adults (>=19 years of age) who participated in the
      2011-2012 Korea National Health and Nutrition Examination Survey (a cross
      sectional and nationally representative survey conducted by the Korean Center for
      Disease Control for Health Statistics), 807 patients with diabetes currently
      taking anti-diabetes medications were excluded from this study. We compared the
      weighted HbA1c levels and weighted proportion (%) of HbA1c levels of >=5.7%,
      >=6.1%, and >=6.5% according to the range of fasting plasma glucose (FPG) levels
      and the presence of IDA.Among 10,665 participants (weighted n = 35,229,108), the
      prevalence of anemia and IDA was 7.3% and 4.3%, respectively. The HbA1c levels
      were higher in participants with IDA (5.70% +/- 0.02%) than in normal
      participants (5.59% +/- 0.01%; P < 0.001), whereas there was no significant
      difference in FPG levels. In participants with an FPG level of <100 mg/dL and 100
      to 125 mg/dL, the weighted HbA1c level was higher in those with IDA (5.59% +/-
      0.02% and 6.00% +/- 0.05%) than in normal participants (5.44% +/- 0.01% and 5.82%
      +/- 0.01%) after adjusting for confounders such as age, sex, FPG level, heavy
      alcohol drinking, waist circumference, and smoking status as well as after
      exclusion of an estimated glomerular filtration rate of <60 mL/min/1.73 m (P <
      0.001, <0.01). The weighted proportions (%) of an HbA1c level of >=5.7% and
      >=6.1% were also higher in participants with IDA than in normal participants (P <
      0.001, <0.05). However, the weighted HbA1c levels in individuals with an FPG
      level >=126 mg/dL and a weighted proportion (%) of an HbA1c level of >=6.5%
      showed no significant differences according to the presence of IDA.In conclusion,
      the presence of IDA shifted the HbA1c level upward only in the normoglycemic and
      prediabetic ranges, not in the diabetic range. Therefore, IDA should be
      considered before using HbA1c as a screening test for prediabetes.

PMID- 25997056
TI  - Female urethral diverticulum containing a giant calculus: a CARE-compliant case
      report.
AB  - Urethral diverticula with calculi have a low incidence as reported in the
      literature. Diverticulum of female urethra is rare, often discovered due to
      associated complications. We report a case of diverticulum of the female urethra
      containing giant calculi in a 62-year-old multiparous woman. She consulted with
      our office due to dysuria and a hard, painful periurethral mass in the anterior
      vagina wall. The diverticulum was approached surgically by a vaginal route, and
      local extraction of the calculi and subsequent diverticulectomy successfully
      treated the condition.Diagnosis of a complicated diverticulum can be easily
      achieved if one possesses a high degree of clinical symptoms.

PMID- 25997057
TI  - Do glioma patients derive any therapeutic benefit from taking a higher cumulative
      dose of temozolomide regimens?: a meta-analysis.
AB  - Temozolomide (TMZ) is an oral alkylating agent with established effects on the
      central nervous system of glioblastoma (GBM) patients. Clinical trials have
      demonstrated a significant impact on overall survival (OS) with TMZ. Ever since,
      several TMZ regimens have been designed to improve treatment efficacy by
      increasing the cumulative dose per cycle. We report a meta-analysis to
      systematically evaluate different treatment schedules of TMZ in GBM patients.All
      searches that were conducted in the Cochrane library, Science Direct, and PubMed
      Databases, and 3 randomized controlled trials (1141 patients) were included. OS
      and progression-free survival (PFS) were the primary outcomes to be
      pooled.Unexpectedly, this analysis did not reveal any OS or PFS advantage for the
      high cumulative dose (HCD) regimen compared with the normal cumulative dose
      regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94-1.22, P =
      0.31). Then after analyzing the characteristics of the results from each trial,
      we found that the regimen with a higher peak concentration during a short-term
      period (daily doses >=150 mg/m/d within <=7 days/cycle) always had a more
      superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI
      of 0.96-1.25 (P = 0.17), which prefers the high peak concentration schedule even
      without a significant difference. The adverse outcome also indicates a
      significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03-2.46, P =
      0.04) among the HCD group.Our study suggests that increasing the cumulative dose
      per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to
      increased risk for leukopenia. Future trials should be designed to examine
      schedules of higher peak concentration rather than the cumulative dose per cycle.

PMID- 25997058
TI  - Intermittent internal fixation with a locking plate to preserve epiphyseal growth
      function during limb-salvage surgery in a child with osteosarcoma of the distal
      femur: a case report.
AB  - Limb shortening is a problem associated with surgery for osteosarcoma of the
      lower extremity in adolescents, as the tumors frequently occur near the
      epiphysis. Herein we report the use of a less invasive stabilization system
      (LISS) and an intermittent fixation method to preserve the growth function of
      epiphysis in an 11-year-old patient with an osteosarcoma of the distal femur.The
      11-year-old male presented with left knee enlargement and pain for 2 weeks, and
      magnetic resonance imaging (MRI) and biopsy were consistent with osteosarcoma of
      the left distal femur. After preoperative chemotherapy, en bloc tumor resection
      was performed with margins based on MRI findings preserving the epiphyseal growth
      plate, the tumor cavity was filled with inactivated bone and bone cement, and a
      LISS was used to stabilize the femur. Aggressive postoperative chemotherapy was
      given. Approximately 105 weeks after surgery radiography showed that the distal
      end of the plate had moved superior to the epiphysis along with bone growth.
      Locking screws were placed in the distal part of the LISS plate to stabilize the
      re-implanted bone, and external fixation was not needed.The patient was able to
      walk with the crutches 1 week postoperatively, and bear weight on the extremity 6
      weeks postoperatively. At 6 years after surgery, the patient's height had
      increased 52 cm, shortening of the affected limb was only 1 cm, and the
      circumference of the affected limb was 2 cm smaller than that of the
      contralateral limb. There was no significant discomfort in the affected limb, and
      there was no gait abnormality. The patient could jump and run, and could
      participate in sports including basketball and badminton to the same degree as
      his peers.In summary, the novel method of bone reconstruction and fixation
      provided good results in a child with an osteosarcoma of the distal femur. This
      fixation method preserves the osteogenic function of the epiphysis and restored
      bone integrity simultaneously, and provides good functional recovery.

PMID- 25997059
TI  - Target gene capture sequencing in Chinese population of sporadic Parkinson
      disease.
AB  - Deciphering of genetic variants plays a critical role in research and clinic of
      genetic disorders, such as the well known neurodegenerative disease Parkinson
      disease (PD). To combine pool of targeted genes and next-generation sequencing
      (NGS), investigators could obtain high efficient but low-cost sequencing data of
      interested genes. Aim to discover genetic variants that might contribute to PD,
      we selected 48 candidate genes involved in different pathways and conducted a
      pilot study to screen nonsynonymous SNPs (nsSNPs) in 4 pooled samples from 237
      sporadic Chinese PD patients. Using our custom-designed NimbleGen array and
      Illumina HiSeq2000, a total of 4 novel nsSNPs (c. 352G>T in STK39, c. 823G>T in
      DGKQ, c. 36T>A in DLA-DRB5, and c. 1981G>T in GRN) were discovered but not
      validated by Sanger sequencing. Additionally, we also selected 6 annotated nsSNPs
      without report in previous PD studies and validated by Sanger sequencing.
      However, genotyping analysis of 6 validated nsSNPs in 50 PD patients and 50
      controls showed no significant differences in cases compared with controls. These
      data represent the first documentation and validation of these mutations in PD
      using target gene capture sequencing. Additional replication studies in other
      populations and functional research are merited to better evaluate precapture
      multiplex protocol and validate the role of the 6 nsSNPs in PD risk.

PMID- 25997060
TI  - Direct medical costs of hospitalizations for cardiovascular diseases in Shanghai,
      China: trends and projections.
AB  - Few studies in China have focused on direct expenditures for cardiovascular
      diseases (CVDs), making cost trends for CVDs uncertain. Epidemic modeling and
      forecasting may be essential for health workers and policy makers to reduce the
      cost burden of CVDs.To develop a time series model using Box-Jenkins methodology
      for a 15-year forecasting of CVD hospitalization costs in Shanghai.Daily visits
      and medical expenditures for CVD hospitalizations between January 1, 2008 and
      December 31, 2012 were analyzed. Data from 2012 were used for further analyses,
      including yearly total health expenditures and expenditures per visit for each
      disease, as well as per-visit-per-year medical costs of each service for CVD
      hospitalizations. Time series analyses were performed to determine the long-time
      trend of total direct medical expenditures for CVDs and specific expenditures for
      each disease, which were used to forecast expenditures until December 31,
      2030.From 2008 to 2012, there were increased yearly trends for both
      hospitalizations (from 250,354 to 322,676) and total costs (from US $ 388.52 to
      721.58 million per year in 2014 currency) in Shanghai. Cost per CVD
      hospitalization in 2012 averaged US $ 2236.29, with the highest being for chronic
      rheumatic heart diseases (US $ 4710.78). Most direct medical costs were spent on
      medication. By the end of 2030, the average cost per visit per month for all CVDs
      was estimated to be US $ 4042.68 (95% CI: US $ 3795.04-4290.31) for all CVDs, and
      the total health expenditure for CVDs would reach over US $1.12 billion (95% CI:
      US $ 1.05-1.19 billion) without additional government interventions.Total health
      expenditures for CVDs in Shanghai are estimated to be higher in the future. These
      results should be a valuable future resource for both researchers on the economic
      effects of CVDs and for policy makers.

PMID- 25997061
TI  - The clinical utility of plasma Epstein-Barr virus DNA assays in nasopharyngeal
      carcinoma: the dawn of a new era?: a systematic review and meta-analysis of 7836
      cases.
AB  - In this study, we assessed the potential of plasma Epstein-Barr virus (EBV) DNA
      assays to predict clinical outcomes in a large sample of nasopharyngeal carcinoma
      (NPC) patients and proposed a risk stratification model based on standardized EBV
      DNA load monitoring.We conducted a meta-analysis of 14 prospective and
      retrospective comparative studies (n = 7 836 patients) to evaluate the
      correlation between pretreatment plasma EBV DNA (pre-DNA), midtreatment plasma
      EBV DNA (mid-DNA), posttreatment plasma EBV DNA (post-DNA), the half-life value
      of plasma EBV DNA clearance rate (t1/2), and clinical outcomes. Our primary
      endpoint was overall survival (OS). Our secondary endpoints were progression-free
      survival (PFS), distant-metastasis-free survival (DMFS), and local-regional
      failure-free survival (LRFS).High pre-DNA, detectable mid-DNA, detectable post
      DNA, and slow EBV DNA clearance rates were all significantly associated with
      poorer OS, with hazard radios (HRs) equal to 2.81, 3.29, 4.26, and 3.58,
      respectively. Pre-DNA, mid-DNA, and post-DNA had the same effects on PFS, DMFS,
      and LRFS.Plasma EBV DNA assays are highly prognostic of long-term survival and
      distant metastasis in NPC patients. Based on the results of this meta-analysis,
      we propose a 4-grade systematic risk stratification model. Given the inherent
      limitations of the included studies, future well-designed randomized clinical
      trials are required to confirm to the findings of this analysis and to contribute
      to the development of individualized treatment strategies for NPC patients.

PMID- 25997062
TI  - Efficacy of coblation technology in treating cervical discogenic upper back pain.
AB  - Upper back pain originating from the cervical disk itself is defined as cervical
      discogenic upper back pain. Coblation procedures can provide therapeutic effects
      for neck and radicular pain related to contained cervical disk herniation.
      However, no studies have reported the performance of coblation procedures,
      particularly for treating cervical discogenic upper back pain. The purpose of
      this study was to evaluate the efficacy of coblation procedures in treating
      cervical discogenic upper back pain.In a prospective, clinical, observational
      study, 28 consecutive patients with discogenic upper back pain underwent
      coblation procedures on the cervical disk with a percutaneous anterior approach.
      Pain visual analogue scale (VAS) scores, patient responses stating significant
      (>=50%) pain relief, significant (>=50%) reduction in pain medicine intake and
      Modified MacNab criteria were adopted to evaluate the pain intensity, degree of
      pain relief, and functional status after 12 months of follow-up.The preoperative
      pain VAS score was 6.5 +/- 1.1 (95% confidence interval [CI] 6.085-6.915), and
      the pain VAS score significantly decreased to 2.4 +/- 1.3 (95% CI 1.929-2.928),
      2.5 +/- 1.5 (95% CI 1.963-3.109), 2.7 +/- 1.4 (95% CI 2.157-3.271), 3.1 +/- 1.6
      (95% CI 2.457-3.686), and 3.1 +/- 1.6 (95% CI 2.471-3.743) at 1 week and 1, 3, 6,
      and 12 months postoperatively, respectively (P < 0.05). Twenty-two (78.6%), 21
      (75.0%), 20 (71.4%), 19 (67.9%), and 18 (64.3%) of the patients expressed
      significant pain relief at 1 week and 1, 3, 6, and 12 months postoperatively,
      respectively. 24 (85.7%), 23 (82.1%), 23 (82.1%), and 22 (78.6%) reported
      significant reduction in pain medication intake at 1, 3, 6, and 12 months
      postoperatively, respectively. According to the Modified MacNab criteria, the
      numbers of patients with "excellent" or "good" ratings were 22 (78.6%), 21
      (75.0%), 20 (71.4%), and 18 (64.3%) at 1, 3, 6, and 12 months postoperatively,
      respectively. No serious complications were observed.The findings of this study
      showed that coblation is an effective, safe, minimally invasive, and less
      uncomfortable procedure for the treatment of discogenic upper back pain.

PMID- 25997063
TI  - Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and
      squamous cell carcinoma.
AB  - In carcinoma, such as of the lung, the histological subtype is important to
      select an appropriate therapeutic strategy for patients. However, carcinomas with
      poor differentiation cannot always be distinguished on the basis of morphology
      alone nor on clinical findings. Hence, delineation of poorly differentiated
      adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin
      carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the
      potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung
      adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs.
      We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no
      expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung
      carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid
      transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for
      squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by
      quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly
      correlated with markers of the adenocarcinomatous lineage. In contrast, little or
      no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines.
      By use of forced expression, or siRNA-mediated depletion of TFF3, we determined
      that TFF3 appeared to maintain rather than promote glandular differentiation of
      lung carcinoma cells. In addition, TFF3 expression was also determined in
      adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among
      all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3
      positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive.
      Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited
      TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3
      positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and
      may function as an additional biomarker for distinguishing adenocarcinoma from
      squamous cell carcinoma.

PMID- 25997064
TI  - Aortic pseudoaneurysm formation following concurrent chemoradiotherapy and
      metallic stent insertion in a patient with esophageal cancer.
AB  - Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT)
      for esophageal cancer patient with esophageal metallic stent insertion is a rare
      condition.A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was
      treated with concurrent weekly cisplatin (30 mg/m) and 5-Fluorouracil (500 mg/m)
      as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal
      metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During
      the treatment regimen, the platelet count dropped to less than 200 * 10 /MUL. One
      month after the completion of CCRT, chest CT revealed the presence of an aortic
      pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic
      endografting was performed and the patient responded well to surgery. However,
      the patient died 2 months later due to a nosocomial infection.Multimodality
      treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal
      metallic stent placement near a great vessel may increase the risk of
      pseudoaneurysm formation.

PMID- 25997065
TI  - Mild angle early onset idiopathic scoliosis children avoid progression under FITS
      method (Functional Individual Therapy of Scoliosis).
AB  - Physiotherapy for stabilization of idiopathic scoliosis angle in growing children
      remains controversial. Notably, little data on effectiveness of physiotherapy in
      children with Early Onset Idiopathic Scoliosis (EOIS) has been published.The aim
      of this study was to check results of FITS physiotherapy in a group of children
      with EOIS.The charts of the patients archived in a prospectively collected
      database were retrospectively reviewed. The inclusion criteria were:diagnosis of
      EOIS based on spine radiography, age below 10 years, both girls and boys, Cobb
      angle between 118 and 308, Risser zero, FITS therapy, no other treatment
      (bracing), and a follow-up at least 2 years from the initiation of the treatment.
      The criterion for curve progression were as follows: the Cobb angle increase of
      68 or more, for curve stabilization; the Cobb angle was 58 comparing to the
      initial radiograph,for curve correction; and the Cobb angle decrease of 68 or
      more at the final follow-up radiograph.There were 41 children with EOIS, 36 girls
      and 5 boys, mean age 7.71.3 years (range 4 to 9 years) who started FITS therapy.
      The curve pattern was single thoracic (5 children), single thoracolumbar (22
      children) or double thoracic/thoracolumbar (14 children), totally 55 structural
      curvatures. The minimum follow-up was 2 years after initiation of the FITS
      treatment, maximum was 16 years, mean 4.8 years). At follow-up the mean age was
      12.53.4 years. Out of 41 children, 10 passed pubertal growth spurt at the final
      follow-up and 31 were still immature and continued FITS therapy. Out of 41
      children, 27 improved, 13 were stable, and one progressed. Out of 55 structural
      curves, 32 improved, 22 were stable and one progressed. For the 55 structural
      curves, the Cobb angle significantly decreased from 18.085.48 at first assessment
      to 12.586.38 at last evaluation,p<0.0001, paired t-test. The angle of trunk
      rotation decreased significantly from 4.782.98 to 3.282.58 at last evaluation,
      p<0.0001,paired t-test.FITS physiotherapy was effective in preventing curve
      progression in children with EOIS. Final postpubertal follow-up data is needed.

PMID- 25997066
TI  - 18F-FDG PET/CT role in staging of gastric carcinomas: comparison with
      conventional contrast enhancement computed tomography.
AB  - The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy
      D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in
      staging gastric cancer comparing it with contrast enhancement computed tomography
      (CECT).This retrospective study included 45 patients who underwent performed
      whole body CECT and F-FDG PET/CT before any treatment. We calculated CECT and F
      FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive
      values (PPV and NPV) for gastric, lymphnode, and distant localizations;
      furthermore, we compared the 2 techniques by McNemar test. The role of F-FDG
      PET/CT semiquantitative parameters in relation to histotype, grading, and site of
      gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy,
      PPV and NPV of CECT, and F-FDG PET/CT for gastric lesion were, respectively,
      92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%,
      46.15%. No differences were identified between the 2 techniques about sensitivity
      and specificity. No statistical differences were observed between PET parameters
      and histotype, grading, and site of gastric lesion. The results of CECT and F-FDG
      PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and
      58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and F-FDG PET/CT
      about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%,
      88.57%, 82.22%, 60%, 88.57%. FDG PET/CT specificity was significantly higher both
      for lymphnode and distant metastases.The F-FDG PET/CT is a useful tool for the
      evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant
      metastases using 1 single image whole-body technique. Integration of CECT with F
      FDG PET/CT permits a more valid staging in these patients.

PMID- 25997067
TI  - Left ventricular relative wall thickness versus left ventricular mass index in
      non-cardioembolic stroke patients.
AB  - In non-cardioembolic stroke patients, the cardiac manifestations of high blood
      pressure are of particular interest. Emerging data suggest that
      echocardiographically determined left ventricular hypertrophy is independently
      associated with risk of ischemic stroke.The primary objective of this study was
      to evaluate the frequency of different patterns of left ventricular (LV)
      remodeling and hypertrophy in a group of consecutive patients admitted with non
      cardioembolic stroke or transient ischemic attack (TIA). In particular, we were
      interested in how often the relative wall thickness (RWT) was abnormal in
      patients with normal LV mass index (LVMI). As both abnormal RWT and LVMI indicate
      altered LV remodeling, the secondary objective of this research was to study
      whether a significant number of patients would be missing the diagnosis of LV
      remodeling if the RWT is not measured.All patients were referred within 48 hours
      after a stroke or a TIA for a clinically indicated transthoracic echocardiogram.
      The echocardiographic findings of consecutive patients with non-cardioembolic
      stroke or TIA were analyzed.All necessary measurements were performed in 368
      patients, who were enrolled in the study. Mean age was 63.7 +/- 12.5 years, 64.4%
      men. Concentric remodeling carried the highest frequency, 49.2%, followed by
      concentric hypertrophy, 30.7%, normal pattern, 15.5%, and eccentric hypertrophy,
      4.1%. The frequency of abnormal left ventricular RWT (80.4%) was significantly
      higher than that of abnormal LVMI (35.3%), (McNemar P < 0.05).In this group of
      non-cardioembolic stroke patients, abnormal LV remodeling as assessed by relative
      wall thickness is very frequent. As RWT was often found without increased LV
      mass, the abnormal left ventricular geometry may be missed if RWT is not measured
      or reported.

PMID- 25997068
TI  - Dysphasia and phantosmia as first presentation of multifocal cerebral anaplastic
      astrocytomas: case report and review of the literatures.
AB  - Multifocal cerebral gliomas (MCGs) represent approximately 10% of gliomas and are
      frequently mistaken as metastases of an unknown primary cancer site. Most MCGs
      are glioblastomas with <4 lesions supratentorially, and are lack of typical
      symptoms and special detections.Through a rare MCG case, we aim to present this
      rarity and emphasize the need to correctly diagnose multiple intracranial lesions
      using a variety of diagnostic modalities to ensure that the patient receives
      proper treatment.We present a case of multifocal cerebral anaplastic astrocytomas
      with a total of 8 lesions located in the left frontal lobe and invading the
      lateral ventricle, presenting with dysphasia and phantosmia. The disease course,
      including diagnosis and treatment, is presented and analyzed in detail. The
      pertinent literature is reviewed regarding this uncommon entity.After an initial
      impression of brain metastasis from lung cancer because of the magnetic resonance
      imaging (MRI) resemblance and history of chronic bronchitis, we were able to use
      positron emission tomography (PET) and excisional biopsy to get the final
      diagnosis. After 10 months, the patient's overall condition deteriorated and
      succumbed to his disease.MCGs are easy to be misdiagnosed as metastatic diseases.
      In addition to MRI, PET adds more biochemical and molecular information and is
      helpful in the differentiation. Although uncommon, if multiple lesions are
      present in various locations in the hemispheres, MCG should be kept in mind.

PMID- 25997069
TI  - Circulating angiopopietin-1 correlates with the clinical course of multiple organ
      dysfunction syndrome and mortality in patients with severe sepsis.
AB  - To determine plasma concentrations of angiopoietin (Ang)-1, Ang-2, Tie-2, and
      vascular endothelial growth factor (VEGF) in patients with sepsis-induced
      multiple organ dysfunction syndrome (MODS) and determine their association with
      mortality.The study prospectively recruited 96 consecutive patients with severe
      sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2,
      Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7
      of sepsis. Univariate and Cox proportional hazards analysis were performed to
      develop a prognostic model.Days 1, 3, and 7 plasma Ang-1 concentrations were
      persistently decreased in MODS patients than in non-MODS patients (day1: 4.0 +/-
      0.5 vs 8.0 +/- 0.5 ng/mL, P < 0.0001; day 3, 3.2 +/- 0.6 vs 7.3 +/- 0.5 ng/mL, P
      < 0.0001, day 7, 2.8 +/- 0.6 vs 10.4 +/- 0.7 ng/mL, P < 0.0001). In patients with
      resolved MODS on day 7 of sepsis, Ang-1 levels were increased from day 1 (4.7 +/-
      0.6 ng/mL vs 9.1 +/- 1.4 ng/mL, n = 43, P = 0.004). Plasma Ang-1 levels were
      lower in nonsurvivors than in survivors on days 1 (4.0 +/- 0.5 vs 7.1 +/- 0.5
      ng/mL, P < 0.0001), 3 (3.8 +/- 0.6 vs 7.1 +/- 0.5 ng/mL, P < 0.0001), and 7 (4.7
      +/- 0.7 vs 11.0 +/- 0.8 ng/mL, P < 0.0001) of severe sepsis. In contrast, plasma
      Ang-2 levels were higher in nonsurvivors than in survivors only on day 1 (15.8 +/
      2.0 vs 9.5 +/- 1.2 ng/mL, P = 0.035). VEGF and Tie-2 levels were not associated
      with MODS and mortality. Ang-1 level less than the median value was the only
      independent predictor of mortality (hazard ratio, 2.57; 95% CI 1.12-5.90, P =
      0.025).Persistently decreased Ang-1 levels are associated with MODS and
      subsequently, mortality in patients with sepsis.

PMID- 25997070
TI  - Effects of phenotypic and genotypic factors on the lipid responses to niacin in
      Chinese patients with dyslipidemia.
AB  - The acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2
      catalyze the final step in triglycerides biosynthesis. This study examined the
      relationships of baseline phenotypes and the common polymorphisms in DGAT1 and
      DGAT2 with the lipid responses to niacin.Lipid responses in Chinese patients with
      dyslipidemia treated with the extended release (ER) niacin/laropiprant
      combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks (n = 121, the
      primary study) or with ER niacin 1500 mg for at least 4 weeks (n = 68, the
      replication study) were analyzed according to genotypes of DGAT1 rs7003945 T>C
      and DGAT2 rs3060 T>C polymorphisms.Treatment with ER niacin improved all lipid
      parameters in both studies. Absolute and percentage changes in lipids were
      related to their baseline levels, particularly for low-density lipoprotein
      cholesterol (LDL-C). The DGAT2 rs3060 T>C polymorphism was associated with lower
      baseline LDL-C, apoB, high-density lipoprotein cholesterol (HDL-C), and apoAI in
      patients on statin therapy in the primary study. Subjects with the DGAT2 rs3060
      T>C variant had less reduction in LDL-C in the primary study and smaller changes
      in triglyceride and HDL-C in the replication study but these associations became
      non-significant after adjusting for baseline lipid values. The DGAT1 rs7003945
      T>C polymorphism was not related to lipid baseline values or changes in either
      study. Concomitant statin therapy and lower body weight were also associated with
      greater reduction in LDL-C.Baseline lipid levels were the main determinants of
      lipid responses especially for LDL-C. The DGAT2 rs3060 polymorphism might
      influence the lipid responses depending on baseline phenotype, but this
      association did not persist after adjustment for the baseline lipid levels.

PMID- 25997071
TI  - Psychometric Properties of the Taiwanese (Traditional Chinese) Version of the
      Frontal Assessment Battery: A Preliminary Study.
AB  - The Frontal Assessment Battery (FAB) is commonly used to evaluate executive
      functions. Although psychometric properties have been examined in Western
      studies, data on the FAB in Eastern societies are limited. This study thus aims
      to examine psychometric properties of the Taiwanese FAB (TFAB). A total of 301
      healthy participants were recruited. All participants were evaluated with the
      TFAB. Thirty participants were retested 3 months after the 1st examination for
      test-retest reliability. The Verbal Fluency Test was used for criterion-related
      validity. Although the TFAB had an unacceptable Cronbach's alpha, its test-retest
      reliability was good. The criterion validity was also good, while the factor
      analysis revealed that the TFAB may be represented as a 2-factor or 3-factor
      structure. The TFAB score was significantly associated with age and education
      level. This study comprehensively re-examined the psychometric properties of the
      TFAB for Chinese-speaking people, and it merited more validations for the TFAB
      with clinical samples in the future. 

PMID- 25997072
TI  - Unveiling the Role of CNTs in the Phase Formation of One-Dimensional
      Ferroelectrics.
AB  - Carbon nanotubes (CNTs) have the potential to act as templates or bottom
      electrodes for three-dimensional (3D) capacitor arrays, which utilize one
      dimensional (1D) ferroelectric nanostructures to increase the memory size and
      density. However, growing a ferroelectric on the surface of CNTs is nontrivial.
      Here, we demonstrate that multiwalled (MW) CNTs decrease the time and temperature
      for the formation of lead zirconium titanate Pb(Zr1-xTix)O3 (PZT) by ~100 
      degrees C commensurate with a decrease in activation energy from 68 +/- 15 to 27
      +/- 2 kJ/mol. As a consequence, monophasic PZT was obtained at 575  degrees C for
      MWCNTs/PZT, but for pure PZT, traces of pyrochlore were still present at 650 
      degrees C, where the PZT phase formed due to homogeneous nucleation. The
      piezoelectric nature of MWCNTs/PZT synthesized at 500  degrees C for 1 h was
      proven. Although further work is required to prove the concept of 3D capacitor
      arrays, our result suggests that it is feasible to utilize MWCNTs as
      templates/electrodes for the formation of 1D PZT nanoferroelectrics. 

PMID- 25997073
TI  - Molecular identification of tuliposide B-converting enzyme: a lactone-forming
      carboxylesterase from the pollen of tulip.
AB  - 6-Tuliposides A (PosA) and B (PosB), which are the major secondary metabolites in
      tulip (Tulipa gesneriana), are enzymatically converted to the antimicrobial
      lactonized aglycons, tulipalins A (PaA) and B (PaB), respectively. We recently
      identified a PosA-converting enzyme (TCEA) as the first reported member of the
      lactone-forming carboxylesterases. Herein, we describe the identification of
      another lactone-forming carboxylesterase, PosB-converting enzyme (TCEB), which
      preferentially reacts with PosB to give PaB. This enzyme was isolated from tulip
      pollen, which showed high PosB-converting activity. Purified TCEB exhibited
      greater activity towards PosB than PosA, which was contrary to that of the TCEA.
      Novel cDNA (TgTCEB1) encoding the TCEB was isolated from tulip pollen. TgTCEB1
      belonged to the carboxylesterase family and was approximately 50% identical to
      the TgTCEA polypeptides. Functional characterization of the recombinant enzyme
      verified that TgTCEB1 catalyzed the conversion of PosB to PaB with an activity
      comparable with the native TCEB. RT-qPCR analysis of each part of plant revealed
      that TgTCEB1 transcripts were limited almost exclusively to the pollen.
      Furthermore, the immunostaining of the anther cross-section using anti-TgTCEB1
      polyclonal antibody verified that TgTCEB1 was specifically expressed in the
      pollen grains, but not in the anther cells. N-terminal transit peptide of TgTCEB1
      was shown to function as plastid-targeted signal. Taken together, these results
      indicate that mature TgTCEB1 is specifically localized in plastids of pollen
      grains. Interestingly, PosB, the substrate of TgTCEB1, accumulated on the pollen
      surface, but not in the intracellular spaces of pollen grains. 

PMID- 25997074
TI  - Prevalence and management of familial hypercholesterolaemia in coronary patients:
      An analysis of EUROASPIRE IV, a study of the European Society of Cardiology.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) is a hereditary disorder
      predisposing to premature coronary heart disease (CHD) and is until now mainly
      diagnosed clinically on the basis of a classical phenotype. Its prevalence varies
      and is estimated around 1 in 200-500; in patients with established CHD the
      prevalence is less well documented. METHODS AND RESULTS: In EUROASPIRE IV data
      were collected in coronary patients from 24 European countries by means of a
      standardized interview, bioclinical examination and venous blood sampling.
      Potential FH was estimated using an adapted version of the Dutch Lipid Clinic
      Network Criteria. Among the 7044 patients eligible for analysis, the prevalence
      of potential FH was 8.3%; 7.5% in men and 11.1% in women. The prevalence was
      inversely related to age with a putative prevalence of 1:5 in those with CHD <50
      yrs of age in both sexes. Even among women aged 70 the prevalence was 1:10.
      Irrespective of age and gender, prevalence differed substantially between
      European regions; potential FH patients were more likely to smoke, had higher
      triglycerides levels and their blood pressure was less well controlled. The use
      of cardioprotective drugs and the prevalences of diabetes, obesity and central
      obesity were similar. CONCLUSIONS: The prevalence of potential FH in coronary
      patients is high; the results underscore the need to promote identification of FH
      in CHD patients and to improve their risk factor profile.

PMID- 25997075
TI  - A bifractal nature of reticular patterns induced by oxygen plasma on polymer
      films.
AB  - Plasma etching was demonstrated to be a promising tool for generating self
      organized nano-patterns on various commercial films. Unfortunately, dynamic
      scaling approach toward fundamental understanding of the formation and growth of
      the plasma-induced nano-structure has not always been straightforward. The
      temporal evolution of self-aligned nano-patterns may often evolve with an
      additional scale-invariance, which leads to breakdown of the well-established
      dynamic scaling law. The concept of a bifractal interface is successfully applied
      to reticular patterns induced by oxygen plasma on the surface of polymer films.
      The reticular pattern, composed of nano-size self-aligned protuberances and
      underlying structure, develops two types of anomalous dynamic scaling
      characterized by super-roughening and intrinsic anomalous scaling, respectively.
      The diffusion and aggregation of short-cleaved chains under the plasma
      environment are responsible for the regular distribution of the nano-size
      protuberances. Remarkably, it is uncovered that the dynamic roughening of the
      underlying structure is governed by a relaxation mechanism described by the
      Edwards-Wilkinson universality class with a conservative noise. The evidence for
      the basic phase, characterized by the negative roughness and growth exponents,
      has been elusive since its first theoretical consideration more than two decades
      ago. 

PMID- 25997076
TI  - Pd-Catalyzed Three-Component Reaction of 3-(Pinacolatoboryl)ally Acetates,
      Aldehydes, and Organoboranes: A New Entry to Stereoselective Synthesis of (Z)
      anti-Homoallylic Alcohols.
AB  - The Pd-catalyzed three-component reaction of 3-(pinacolatoboryl)allyl acetates,
      aldehydes, and organoboranes is described. The reaction is initiated by the
      formation of an allylic gem-palladium/boryl intermediate, which then undergoes
      allylation of aldehydes by allylboronates followed by a coupling reaction of in
      situ generated (Z)-vinylpalladium acetates with organoboranes to provide the (Z)
      anti-homoallylic alcohols with high levels of diastereoselectivity and alkene
      stereocontrol. 

PMID- 25997077
TI  - Two-Piece Hollow Bulb Obturator for Postsurgical Partial Maxillectomy Defect in a
      Young Patient Revamping Lost Malar Prominence: A Clinical Report.
AB  - The most frequent type of treatment for patients diagnosed with a malignant
      neoplasia of the oral cavity is surgical resection of the tumor. Ablative surgery
      may be followed by a reconstructive phase, in which the surgeon may choose
      between local flaps, nonvascularized bone grafts or free vascularized flaps to
      close the surgical site, depending on the general conditions of the patient.
      Esthetic and functional results are challenging to achieve for the
      prosthodontist, as variable amount of hard and soft tissues are removed. This
      report describes the fabrication of a two-piece hollow obturator for a 19-year
      old patient who underwent wide surgical excision of the osteosarcoma of the
      maxilla and was rehabilitated to function. In this case, the surgical site was
      covered with submental flap, and the second piece of the obturator provided
      fullness to the lost malar prominence. 

PMID- 25997079
TI  - Case of bilateral acroangiodermatitis due to symmetrical arteriovenous fistulas
      of the soles.
AB  - A 58-year-old woman presented painful chronic inflammation of the outside skin of
      the bilateral soles. A skin biopsy revealed chronic inflammation of the dermis
      and subcutaneous tissue, as well as the marked dilatation and proliferation of
      capillaries and veins, and the thick deposition of elastic fibers around the
      thick-walled veins. 3-D contrasted computed tomography of the lower extremities
      demonstrated early bilateral imaging of the veins, and fistulas of the peroneal
      as well as posterior tibial artery and vein of the bilateral soles. On the basis
      of a diagnosis of bilateral acroangiodermatitis due to symmetrical arteriovenous
      fistulas, the patient underwent compression therapy using elastic bandages, and
      the symptoms reduced in several days. 

PMID- 25997078
TI  - A genome-wide sib-pair scan for quantitative language traits reveals linkage to
      chromosomes 10 and 13.
AB  - Although there is considerable evidence that individual differences in language
      development are highly heritable, there have been few genome-wide scans to locate
      genes associated with the trait. Previous analyses of language impairment have
      yielded replicable evidence for linkage to regions on chromosomes 16q, 19q, 13q
      (within lab) and at 13q (between labs). Here we report the first linkage study to
      screen the continuum of language ability, from normal to disordered, as found in
      the general population. 383 children from 147 sib-ships (214 sib-pairs) were
      genotyped on the Illumina((r)) Linkage IVb Marker Panel using three composite
      language-related phenotypes and a measure of phonological memory (PM). Two
      regions (10q23.33; 13q33.3) yielded genome-wide significant peaks for linkage
      with PM. A peak suggestive of linkage was also found at 17q12 for the overall
      language composite. This study presents two novel genetic loci for the study of
      language development and disorders, but fails to replicate findings by previous
      groups. Possible reasons for this are discussed. 

PMID- 25997080
TI  - Long-term Outcomes After Stepping Down Asthma Controller Medications: A Claims
      Based, Time-to-Event Analysis.
AB  - BACKGROUND: Long-term outcomes after stepping down asthma medications are not
      well described. METHODS: This study was a retrospective time-to-event analysis of
      individuals diagnosed with asthma who stepped down their asthma controller
      medications using a US claims database spanning 2000 to 2012. Four-month
      intervals were established and a step-down event was defined by a >= 50% decrease
      in days-supplied of controller medications from one interval to the next; this
      definition is inclusive of step-down that occurred without health-care provider
      guidance or as a consequence of a medication adherence lapse. Asthma stability in
      the period prior to step-down was defined by not having an asthma exacerbation
      (inpatient visit, ED visit, or dispensing of a systemic corticosteroid linked to
      an asthma visit) and having fewer than two rescue inhaler claims in a 4-month
      period. The primary outcome in the period following step-down was time-to-first
      asthma exacerbation. RESULTS: Thirty-two percent of the 26,292 included
      individuals had an asthma exacerbation in the 24-month period following step-down
      of asthma controller medication, though only 7% had an ED visit or
      hospitalization for asthma. The length of asthma stability prior to stepping down
      asthma medication was strongly associated with the risk of an asthma exacerbation
      in the subsequent 24-month period: < 4 months' stability, 44%; 4 to 7 months,
      34%; 8 to 11 months, 30%; and >= 12 months, 21% (P < .001). CONCLUSIONS: In a
      large, claims-based, real-world study setting, 32% of individuals have an asthma
      exacerbation in the 2 years following a step-down event.

PMID- 25997081
TI  - Social adversity and regional differences in prescribing of ADHD medication for
      school-age children.
AB  - OBJECTIVES: To explore whether regional variations in the initiation of attention
      deficit hyperactivity disorder (ADHD) medication among school-age children are
      explained by differences in sociodemographic composition and/or ADHD prescribing
      practice, especially in children who face social adversity (low parental
      education and single parenthood). METHODS: A cohort of Danish school-age children
      (ages 5-17) without previous psychiatric conditions (N = 813,416) was followed
      during 2010-2011 for incident ADHD prescribing in the individual-level Danish
      registers. Register information was retrieved for both children and their
      parents. Regional differences were decomposed into contributions from differences
      in sociodemographic composition and in prescribing practices. Incidence rate
      ratios (IRR) with 95% confidence interval (CI) of ADHD prescribing were
      calculated using demographically standardized multivariable Poisson regression
      models. RESULTS: Compared with the Capital, prescribing rates were significantly
      higher in regions North and Zealand (IRR, 1.19; 95% CI, 1.08-1.32 and 1.17; 1.08
      1.28, respectively) and lower in South (IRR, 0.60; 95% CI, 0.54-0.66). After
      inclusion of the interaction term (region*social adversity), the multivariable
      analyses revealed a higher rate for the most disadvantaged children in North
      (IRR, 2.00; 95% CI, 1.51-2.66) and a lower rate in South (IRR, 0.47; 95% CI, 0.3
      0.65). Prescribing rates were the highest for disadvantaged children in all
      regions, demonstrating the steepest social gradient in North and the smoothest in
      South. Demographic composition explained little of the variation: 3% for North
      and 13% for Zealand. CONCLUSIONS: Differences in sociodemographic composition
      explain little of regional variation in incident ADHD prescribing for children.
      However, large regional differences prevail in prescribing practices for children
      facing social adversity, indicating that local cultures shape the interpretation
      and handling of children with ADHD-like behaviors.

PMID- 25997082
TI  - Identification of miRNAs and Their Target Genes Associated with Sweet Corn Seed
      Vigor by Combined Small RNA and Degradome Sequencing.
AB  - High seed vigor is significant for agriculture. Low seed vigor of sweet corn
      hindered the popularization of sweet corn (Zea mays L. saccharata Sturt). To
      better understand the involvement and regulatory mechanism of miRNAs with seed
      vigor, small RNA libraries from seeds non-artificially aged and artificially aged
      for 2 days were generated by small RNA sequencing. A total of 27 differentially
      expressed miRNAs were discovered, of which 10 were further confirmed by real-time
      quantitative polymerase chain reaction. Furthermore, targets of miRNAs were
      identified by degradome sequencing. A total of 1142 targets that were potentially
      cleaved by 131 miRNAs were identified. Gene ontology (GO) annotations of target
      transcripts indicated that 26 target genes cleaved by 9 differentially expressed
      miRNAs might play roles in the regulation of seed vigor, such as peroxidase
      superfamily protein targeted by PC-5p-213179_17 playing a role in the oxidation
      reduction process and response to oxidative stress. These findings provide
      valuable information to understand the involvement of miRNAs with seed vigor. 

PMID- 25997083
TI  - Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with
      Different Surface Characteristics and Sizes in Excised Porcine Olfactory
      Epithelium.
AB  - The ability to deliver therapeutically relevant amounts of drugs directly from
      the nasal cavity to the central nervous system to treat neurological diseases is
      dependent on the availability of efficient drug delivery systems. Increased
      delivery and/or therapeutic effect has been shown for drugs encapsulated in
      nanoparticles; however, the factors governing the transport of the drugs and/or
      the nanoparticles from the nasal cavity to the brain are not clear. The present
      study evaluates the potential transport of nanoparticles across the olfactory
      epithelium in relation to nanoparticle characteristics. Model systems, 20, 100,
      and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were
      nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS),
      were assessed for transport across excised porcine olfactory epithelium mounted
      in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the
      donor chamber of the diffusion cell, accompanied by fluorescence microscopy of
      dismounted tissues, revealed a loss of nanoparticle content from the donor
      suspension and their association with the excised tissue, depending on the
      surface properties and particle size. Chitosan surface modification of PS
      nanoparticles resulted in the highest tissue association among the tested
      systems, with the associated nanoparticles primarily located in the mucus,
      whereas the polysorbate 80-modified nanoparticles showed some penetration into
      the epithelial cell layer. Assessment of the bioelectrical properties, metabolic
      activity, and histology of the excised olfactory epithelium showed that C-PS
      nanoparticles applied in pH 6.0 buffer produced a damaging effect on the
      epithelial cell layer in a size-dependent manner, with fine 20 nm sized
      nanoparticles causing substantial tissue damage relative to that with the 100 and
      200 nm counterparts. Although histology showed that the olfactory tissue was
      affected by the application of citrate buffer that was augmented by addition of
      chitosan in solution, this was not reflected in the bioelectrical parameters and
      the metabolic activity of the tissue. Regarding transport across the excised
      olfactory tissue, none of the nanoparticle systems tested, irrespective of
      particle size or surface modification, was transported across the epithelium to
      appear in measurable amounts in the receiver chamber. 

PMID- 25997084
TI  - Epigenetic Modulators Enhance Constitutive and Liver-Specific Reporter Expression
      in Murine Liver Progenitor Cell Lines.
AB  - Stem cells expressing reporter constructs are extremely useful for their tracking
      in vivo or for determining cell lineage fate in vivo and in vitro. We generated
      liver progenitor cell (LPC) lines from actin-EGFP and TAT-GRE-lacZ mice. LPCs
      from the actin-EGFP mouse facilitate cell tracing following transplant as the
      reporter is constitutively expressed. LPCs from the TAT-GRE-lacZ mouse express
      beta-galactosidase under the control of the tyrosine aminotransferase (TAT)
      promoter and are only active in mature hepatocytes. We found that the utility of
      such LPC lines becomes severely limited by downregulation of transgene expression
      following extended culture. We show that epigenetic mechanisms are responsible
      for suppressing expression of both transgenes. Enhancement of transgene
      expression in both LPC lines was achieved by treating the cell lines with either
      the histone acetylating agent sodium butyrate or the DNA demethylating agent 5
      azacytidine. 

PMID- 25997085
TI  - Toward High Performance n-Type Thermoelectric Materials by Rational Modification
      of BDPPV Backbones.
AB  - Three n-type polymers BDPPV, ClBDPPV, and FBDPPV which exhibit outstanding
      electrical conductivities when mixed with an n-type dopant, N-DMBI ((4-(1,3
      dimethyl-2,3-dihydro-1H-benzoimidazol-2-yl)phenyl)dimethylamine), in solution.
      High electron mobility and an efficient doping process endow FBDPPV with the
      highest electrical conductivities of 14 S cm(-1) and power factors up to 28 MUW
      m(-1) K(-2), which is the highest thermoelectric (TE) power factor that has been
      reported for solution processable n-type conjugated polymers. Our investigations
      reveal that introduction of halogen atoms to the polymer backbones has a dramatic
      influence on not only the electron mobilities but also the doping levels, both of
      which are critical to the electrical conductivities. This work suggests the
      significance of rational modification of polymer structures and opens the gate
      for applying the rapidly developed organic semiconductors with high carrier
      mobilities to thermoelectric field. 

PMID- 25997088
TI  - Postoperative prostate-specific antigen monitoring interval for radical
      prostatectomy patients with low recurrence risk.

PMID- 25997086
TI  - Gene expression homeostasis and chromosome architecture.
AB  - In rapidly growing populations of bacterial cells, including those of the model
      organism Escherichia coli, genes essential for growth--such as those involved in
      protein synthesis--are expressed at high levels; this is in contrast to many
      horizontally-acquired genes, which are maintained at low transcriptional levels.
      (1) This balance in gene expression states between 2 distinct classes of genes is
      established by a galaxy of transcriptional regulators, including the so-called
      nucleoid associated proteins (NAP) that contribute to shaping the chromosome. (2)
      Besides these active players in gene regulation, it is not too far-fetched to
      anticipate that genome organization in terms of how genes are arranged on the
      chromosome, (3) which is the result of long-drawn transactions among genome
      rearrangement processes and selection, and the manner in which it is structured
      inside the cell, plays a role in establishing this balance. A recent study from
      our group has contributed to the literature investigating the interplay between
      global transcriptional regulators and genome organization in establishing gene
      expression homeostasis. (4) In particular, we address a triangle of functional
      interactions among genome organization, gene expression homeostasis and
      horizontal gene transfer.

PMID- 25997090
TI  - The Effect of Repetition Rate on Air-Conducted Ocular Vestibular Evoked Myogenic
      Potentials (oVEMPs).
AB  - PURPOSE: Ocular vestibular evoked myogenic potentials (oVEMPs) are used to
      describe utricular/superior vestibular nerve function; however, optimal recording
      parameters have not been fully established. This study investigated the effect of
      repetition rate on air-conducted oVEMPs. METHOD: Ten healthy adults were
      evaluated using 500-Hz tone bursts (4-ms duration, Blackman gating, 122 dB pSPL).
      Four repetition rates were used (1.6, 4.8, 8.3, and 26.6 Hz) and resulting oVEMP
      response presence, amplitude, amplitude asymmetry, and n1/p1 latency were
      assessed. RESULTS: Response presence was significantly reduced for 26.6 Hz using
      monaural stimulation and for 8.3 Hz and 26.6 Hz for binaural stimulation. For
      monaural stimulation using 1.6, 4.8, and 8.3 Hz, no significant differences were
      noted for amplitude or latency. Responses obtained using binaural stimulation
      demonstrated a significant effect of rate on amplitude, with 8.3 Hz producing
      significantly reduced amplitude. Binaural amplitudes were significantly larger
      than monaural contralateral responses but with reduced response presence. No
      significant differences were noted for latency or amplitude asymmetry.
      CONCLUSION: Using repetition rates of approximately 5 Hz or less may produce more
      consistent oVEMP response presence with minimal effects on amplitude for monaural
      or binaural recordings.

PMID- 25997091
TI  - [Giant Molluscum Contagiosum Eyelid Lesions as a Solid Tumour].

PMID- 25997092
TI  - [Prospective Reliability Trial to Assess Inter and Intra Observer Reliability of
      Rebound Tonometry in the Eyes of Healthy Probands].
AB  - PURPOSE: A prospective reliability trial was implemented to estimate the inter-
      and intraobserver reproducibility of iCare(r) rebound tonometry in healthy
      proband eyes. MATERIAL AND METHODS: Three independent observers performed three
      replicate measurements, respectively, by means of the iCare(r)PRO rebound
      tonometry device in 20 eyes of 20 healthy probands. Two of these observers were
      medical doctors with an at least two years experience in ophthalmological patient
      care, the third observer was a study nurse with several years practice in
      applying ophthalmological diagnostic procedures. Each observer's replicate
      measurements were averaged and then compared by means of a global Friedman test
      for interobserver bias in the parallel rebound tonometry measurements at the 5 %
      significance level. In addition, variance component analysis was performed on the
      overall repeated measurement design to estimate the iCare(r) reliability
      coefficient [%] (100 % indicating total reproducibility in absence of any inter
      or intra observer bias). RESULTS: The respective observers' median average
      measurements were 15.9 mmHg (interquartile range 15.1 to 17.5 mmHg) and 15.1 mmHg
      (14.3 to 15.6 mmHg) for the medical doctors, furthermore 16.8 mmHg (14.2 to 18.9
      mmHg) for the study nurse; the averaged measurement series showed a significant
      interobserver bias (Friedman p = 0.006). Variance component analysis revealed an
      overall iCare(r) reliability of 35 % (95 % confidence interval 26 to 44 %).
      CONCLUSION: In this repeated measurement design iCare(r) rebound tonometry
      measurements showed significant interobserver bias and thereby notably reduced
      overall reliability. In particular, the intraindividual measurement profiles
      showed a gradient towards smaller values during the 9 replicates' series;
      furthermore the study nurses' measurements showed notably increased variability.
      As a consequence the routine use of iCare(r) rebound tonometry must be critically
      discussed at least when being delegated to less experienced staff.

PMID- 25997093
TI  - [The Effect of Non-Depolarising Muscle Relaxants on Ocular Pulse Amplitude and
      Intraocular Pressure].
AB  - AIM: In general anaesthesia (GA) for ocular surgery the chosen non-depolarising
      muscle relaxant has a high influence on the fluctuations of intraocular pressure
      (IOP) and ocular pulse amplitude (OPA). PATIENTS AND METHODS: In 229 patients,
      who needed GA for their ophthalmic surgery, OPA and IOP were measured with the
      dynamic contour tonometer (DCT) before and 5 minutes after intubation. For GA,
      three groups of non-depolarising muscle relaxants, namely, mivacurium (n = 71),
      atracurium (n = 91) and rocuronium (n = 67) were used. RESULTS: The IOP decreased
      by about 4.0 +/- 2.3 mmHg using mivacurium in GA, by about 6.1 +/- 2.2 mmHg using
      atracurium and by about 7.4 +/- 1.7 mmHg using rocuronium (p < 0.001). The
      relative decrease of the IOP was 20% for mivacurium, 31% for atracurium and 37%
      for rocuronium. For mivacurium the OPA decreased from 3.4 +/- 1.5 mmHg to 2.2 +/-
      1.1 mmHg (p < 0.001) in contrast to atracurium (decrease from 3.6 +/- 1.5 mmHg to
      1.8 +/- 0.8 mmHg; p < 0.001) and rocuronium (decrease from 3.1 +/- 1.6 mmHg to
      1.7 +/- 0.9 mmHg; p < 0.001). Mean OPA reduction was lowest with mivacurium (1.3
      mmHg) and the highest with atracurium (1.7 mmHg). The mean relative decrease of
      the OPA was 34% with mivacurium, 46% with atracurium and 43% with rocuronium (p <
      0.001). There was no linear correlation between the relative OPA decrease and the
      relative IOP decrease. CONCLUSION: Risks for ophthalmic surgery may be minimised
      by avoiding mivacurium in general anaesthesia. Due to its negative effects on IOP
      and OPA mivacurium does not seem to be suitable for operations with a large
      opening in the eye such as penetrating keratoplasty and block excision.
      Rocuronium can be used because it induces a favourised intraoperative decrease of
      the IOP.

PMID- 25997094
TI  - Treatment of intraparenchymal hypertension with hyperosmotic therapy: hypertonic
      saline 7.45% vs. mannitol 20.
AB  - BACKGROUND: There is controversy about the superiority of hypertonic saline (HS)
      over mannitol (M) to treat intracranial hypertension (ICHT). We aim to compare
      the effects of HS 7.45% vs. M 20% on systemic hemodynamics, intracranial pressure
      (ICP) and brain regional metabolism or oxygenation during experimental ICHT.
      METHODS: In 16 sedated and mechanically-ventilated pigs, ICHT was obtained by
      inflation of a balloon catheter inserted in the right frontal lobe. Ventilation
      was set to maintain normoxia and normocapnia. Mean arterial pressure was
      maintained above 80 mmHg by IV isotonic fluids. Animals were randomized to
      receive a 30-minute IV load of 255 mOsm/dose of either HS 7.45% (N.=7) or M 20%
      (N.=7). Brain oxygen tension (PbO2) was measured hourly by a parenchymal Clark
      electrode and cerebral lactate/pyruvate ratio (LPR) was assessed using brain
      microdialysis. A linear mixed model was used to analyze the time course of
      considered variables from baseline to 180 minutes after infusion. RESULTS: There
      was no significant difference in systemic hemodynamics between the two groups
      over the study period. HS 7.45% administration maintained a lower ICP and a
      higher cerebral perfusion pressure at 180 minutes, but with no significant
      difference in PbO2 or LPR. CONCLUSIONS: In this model of ICHT, only small
      differences were found in maintaining a better cerebral perfusion using HS 7.45%
      compared to M 20% in the early phase of therapy. These differences were not
      dependent on changes in systemic hemodynamics and did not result in significant
      differences in brain regional oxygenation or metabolism.

PMID- 25997095
TI  - Molecular mechanism of silver nanoparticles in human intestinal cells.
AB  - Silver nanoparticles are used in consumer products like food contact materials,
      drinking water technologies and supplements, due to their antimicrobial
      properties. This leads to an oral uptake and exposure of intestinal cells. In
      contrast to other studies we found no apoptosis induction by surfactant-coated
      silver nanoparticles in the intestinal cell model Caco-2 in a previous study,
      although the particles induced oxidative stress, morphological changes and cell
      death. Therefore, this study aimed to analyze the molecular mechanism of silver
      nanoparticles in Caco-2 cells. We used global gene expression profiling in
      differentiated Caco-2 cells, supported by verification of the microarray data by
      quantitative real-time RT-PCR and microscopic analysis, impedance measurements
      and assays for apoptosis and oxidative stress. Our results revealed that
      surfactant-coated silver nanoparticles probably affect the cells by outside-in
      signaling. They induce oxidative stress and have an influence on canonical
      pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight
      junctions, thereby inducing transcription factors like AP1, NFkB and NRF2, which
      mediate cellular reactions in response to oxidative stress and metal ions and
      induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The
      present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic
      cell death, especially in the intestine, can cause inflammation and influence the
      mucosal immune response. 

PMID- 25997096
TI  - Cognitive Abilities Underlying Reading Accuracy, Fluency and Spelling Acquisition
      in Korean Hangul Learners from Grades 1 to 4: A Cross-Sectional Study.
AB  - The purpose of this cross-sectional study was to examine the cognitive abilities
      that predict reading and spelling performance in Korean children in Grades 1 to
      4, depending on expertise and reading experience. As a result, visual cognition,
      phonological awareness, naming speed and receptive vocabulary significantly
      predicted reading accuracy in children in Grades 1 and 2, whereas visual
      cognition, phonological awareness and rapid naming speed did not predict reading
      accuracy in children in higher grades. For reading, fluency, phonological
      awareness, rapid naming speed and receptive vocabulary were crucial abilities in
      children in Grades 1 to 3, whereas phonological awareness was not a significant
      predictor in children in Grade 4. In spelling, reading ability and receptive
      vocabulary were the most important abilities for accurate Hangul spelling. The
      results suggested that the degree of cognitive abilities required for reading and
      spelling changed depending on expertise and reading experience.

PMID- 25997097
TI  - The effect of various atomic partial charge schemes to elucidate consensus
      activity-correlating molecular regions: a test case of diverse QSAR models.
AB  - The estimation of atomic partial charges of the small molecules to calculate
      molecular interaction fields (MIFs) is an important process in field-based
      quantitative structure-activity relationship (QSAR). Several studies showed the
      influence of partial charge schemes that drastically affects the prediction
      accuracy of the QSAR model and focused on the selection of appropriate charge
      models that provide highest cross-validated correlation coefficient ([Formula:
      see text] or q(2)) to explain the variation in chemical structures against
      biological endpoints. This study shift this focus in a direction to understand
      the molecular regions deemed to explain SAR in various charge models and
      recognize a consensus picture of activity-correlating molecular regions. We
      selected eleven diverse dataset and developed MIF-based QSAR models using various
      charge schemes including Gasteiger-Marsili, Del Re, Merck Molecular Force Field,
      Huckel, Gasteiger-Huckel, and Pullman. The generalized resultant QSAR models were
      then compared with Open3DQSAR model to interpret the MIF descriptors decisively.
      We suggest the regions of activity contribution or optimization can be
      effectively determined by studying various charge-based models to understand SAR
      precisely. 

PMID- 25997098
TI  - The role of guilt in the development of post-traumatic stress disorder: A
      systematic review.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) can be a debilitating condition
      associated with a myriad of emotions. Guilt is an important associated feature of
      PTSD that has received far less recognition than other symptoms often associated
      with fear and intense threat. The nature of the relationship between guilt and
      PTSD remains elusive and requires further clarification. The aim of the current
      paper was to review the extant literature regarding the link between guilt and
      PTSD. METHOD: A systematic database search of PsycINFO, Medline, Embase and Web
      of Science identified articles that enabled examination of the guilt-PTSD
      relationship. A total of 27 articles met inclusion criteria for this review.
      RESULTS: There were cross-sectional relationships between guilt and PTSD
      symptomology with evidence of associations between PTSD symptoms and cognitions
      related to perceived wrong doing and self-blame. However, the direction of
      association between guilt and PTSD is unclear and possibly confounded by
      overlapping constructs such as shame. LIMITATIONS: The review is constrained by
      the absence of longitudinal and experimental research and studies, which control
      for potential confounding variables. The reliability and validity of measures of
      guilt and PTSD is also not consistently reported. CONCLUSION: This review
      outlines four competing models of the guilt-PTSD relationship and examines
      existing evidence linking the two constructs. The current literature is too
      preliminary to offer any strong support for one model over the other. However, in
      critically appraising existing studies, this review helps to inform the design of
      future studies investigating the association between guilt and PTSD.

PMID- 25997099
TI  - Structure of a type IV pilus machinery in the open and closed state.
AB  - Proteins of the secretin family form large macromolecular complexes, which
      assemble in the outer membrane of Gram-negative bacteria. Secretins are major
      components of type II and III secretion systems and are linked to extrusion of
      type IV pili (T4P) and to DNA uptake. By electron cryo-tomography of whole
      Thermus thermophilus cells, we determined the in situ structure of a T4P
      molecular machine in the open and the closed state. Comparison reveals a major
      conformational change whereby the N-terminal domains of the central secretin PilQ
      shift by ~30 A, and two periplasmic gates open to make way for pilus extrusion.
      Furthermore, we determine the structure of the assembled pilus.

PMID- 25997100
TI  - Distinct cortical codes and temporal dynamics for conscious and unconscious
      percepts.
AB  - The neural correlates of consciousness are typically sought by comparing the
      overall brain responses to perceived and unperceived stimuli. However, this
      comparison may be contaminated by non-specific attention, alerting, performance,
      and reporting confounds. Here, we pursue a novel approach, tracking the neuronal
      coding of consciously and unconsciously perceived contents while keeping behavior
      identical (blindsight). EEG and MEG were recorded while participants reported the
      spatial location and visibility of a briefly presented target. Multivariate
      pattern analysis demonstrated that considerable information about spatial
      location traverses the cortex on blindsight trials, but that starting ~270 ms
      post-onset, information unique to consciously perceived stimuli, emerges in
      superior parietal and superior frontal regions. Conscious access appears
      characterized by the entry of the perceived stimulus into a series of additional
      brain processes, each restricted in time, while the failure of conscious access
      results in the breaking of this chain and a subsequent slow decay of the
      lingering unconscious activity. 

PMID- 25997104
TI  - Strengthening the Link between Life Cycle Assessment and Indicators for Absolute
      Sustainability To Support Development within Planetary Boundaries.

PMID- 25997102
TI  - Self-Reported Sexual Function Measures Administered to Female Cancer Patients: A
      Systematic Review, 2008-2014.
AB  - A systematic review was conducted to identify and characterize self-reported
      sexual function (SF) measures administered to women with a history of cancer.
      Using 2009 PRISMA guidelines, we searched electronic bibliographic databases for
      quantitative studies published January 2008-September 2014 that used a self
      reported measure of SF, or a quality of life (QOL) measure that contained at
      least 1 item pertaining to SF. Of 1,487 articles initially identified, 171 were
      retained. The studies originated in 36 different countries with 23% from US-based
      authors. Most studies focused on women treated for breast, gynecologic, or
      colorectal cancer. About 70% of the articles examined SF as the primary focus;
      the remaining examined QOL, menopausal symptoms, or compared treatment
      modalities. We identified 37 measures that assessed at least one domain of SF,
      eight of which were dedicated SF measures developed with cancer patients. Almost
      one third of the studies used EORTC QLQ modules to assess SF, and another third
      used the Female Sexual Function Inventory. There were few commonalities among
      studies, though nearly all demonstrated worse SF after cancer treatment or
      compared to healthy controls. QOL measures are better suited to screening while
      dedicated SF questionnaires provide data for more in depth assessment. This
      systematic review will assist oncology clinicians and researchers in their
      selection of measures of SF and encourage integration of this quality of life
      domain in patient care. 

PMID- 25997103
TI  - The five-year incidence of open globe eye injuries at Odense University Hospital,
      Denmark.

PMID- 25997101
TI  - QIL1 is a novel mitochondrial protein required for MICOS complex stability and
      cristae morphology.
AB  - The mitochondrial contact site and cristae junction (CJ) organizing system
      (MICOS) dynamically regulate mitochondrial membrane architecture. Through
      systematic proteomic analysis of human MICOS, we identified QIL1 (C19orf70) as a
      novel conserved MICOS subunit. QIL1 depletion disrupted CJ structure in cultured
      human cells and in Drosophila muscle and neuronal cells in vivo. In human cells,
      mitochondrial disruption correlated with impaired respiration. Moreover,
      increased mitochondrial fragmentation was observed upon QIL1 depletion in flies.
      Using quantitative proteomics, we show that loss of QIL1 resulted in MICOS
      disassembly with the accumulation of a MIC60-MIC19-MIC25 sub-complex and
      degradation of MIC10, MIC26, and MIC27. Additionally, we demonstrated that in
      QIL1-depleted cells, overexpressed MIC10 fails to significantly restore its
      interaction with other MICOS subunits and SAMM50. Collectively, our work uncovers
      a previously unrecognized subunit of the MICOS complex, necessary for CJ
      integrity, cristae morphology, and mitochondrial function and provides a resource
      for further analysis of MICOS architecture. 

PMID- 25997105
TI  - Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk
      factors and prognostic role.
AB  - BACKGROUND: Although atrial fibrillation (AF) is a known complication of
      amyloidotic cardiomyopathy (AC), a precise pathophysiological and prognostic
      characterization is not available. We therefore aimed to assess prevalence,
      incidence, risk factors and prognostic significance of AF in light-chain (AL),
      hereditary transthyretin-related (m-ATTR) and non-mutant transthyretin-related
      (wt-ATTR) AC. METHODS: Retrospective study of 262 patients with AC (123 AL, 94 m
      ATTR, 45 wt-ATTR) from a single center. RESULTS: AF prevalence was 15% (AL 9%, m
      ATTR 11%, wt-ATTR 40%). During a median follow-up of 1.2 years 11 patients
      developed AF (2.1% person-years). Age, heart failure (HF), left ventricular (LV)
      ejection fraction, renal involvement, left atrial size and right atrial pressure
      were independently associated with AF. AF was associated with incident HF but not
      with increased mortality. All AF patients were prescribed warfarin and none
      suffered thromboembolic events. CONCLUSIONS: In AC the prevalence of AF varies
      widely according to etiology with a mean value of 15% that reaches 40% in wt-ATTR
      amyloidosis. Age, HF, LV ejection fraction, left atrial size and right atrial
      pressure were the main independent risk factors, while wall thickness and
      etiology were not the main independent risk factors. AF does not seem to impact
      all-cause mortality but was strongly associated with prevalent and incident HF.

PMID- 25997106
TI  - Early MRD response as a prognostic factor in adult patients with acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: To evaluate the prognostic power of minimal residual disease (MRD)
      monitored by polymerase chain reaction at defined time points during early
      treatment in adult patients with acute lymphoblastic leukemia (ALL). METHODS:
      Seventy-one patients were treated according to the GMALL 07/2003 protocol and
      evaluated for MRD in bone marrow by specific clonal rearrangements of Ig/TCR in
      BCR-ABL negative ALL or fusion gene transcript in BCR-ABL positive ALL. RESULTS:
      Three-year overall survival (OS) was 94% in patients with BCR-ABL negative ALL
      reaching complete molecular response (CMR) after the first course of chemotherapy
      (vs. 32% if MRD >10(-4) ; P = 0.001). Patients with CMR prior to the start of
      consolidation chemotherapy at week 11 had 3-yr OS 82% (vs. 18% if MRD >10(-4) ; P
      = 0.001). Patients with BCR-ABL positive ALL showed slower MRD dynamics. There
      was a trend to better OS in patients with >= 4 log reduction of BCR-ABL
      transcript prior to HSCT (92% vs. 50%; P = 0.065). None of the patients with
      detectable MRD (both BCR-ABL positive and negative) after HSCT survived 3 yr.
      CONCLUSION: Early MRD kinetics is an important tool for new prognostication
      models with direct clinical impact irrespective of standard prognostic factors in
      patients with BCR-ABL negative ALL.

PMID- 25997107
TI  - A simple evaluation of soil quality of waterlogged purple paddy soils with
      different productivities.
AB  - Evaluation of soil quality can be crucial for designing efficient farming systems
      and ensuring sustainable agriculture. The present study aimed at evaluating the
      quality of waterlogged purple paddy soils with different productivities in
      Sichuan Basin. The approach involved comprehensive analyses of soil physical and
      chemical properties, as well as enzyme activities and microbial community
      structure measured by phospholipid fatty acid analysis (PLFA). A total of 36 soil
      samples were collected from four typical locations, with 12 samples representing
      high productivity purple paddy soil (HPPS), medium productivity purple paddy soil
      (MPPS) and low productivity purple paddy soil (LPPS), respectively. Most measured
      soil properties showed significant differences (P <= 0.05) among HPPS, MPPS and
      LPPS. Pearson correlation analysis and principal component analysis were used to
      identify appropriate soil quality indicators. A minimum data set (MDS) including
      total nitrogen (TN), available phosphorus (AP), acid phosphatase (ACP), total
      bacteria (TB) and arbuscular mycorrhizal fungi was established and accounted for
      82.1% of the quality variation among soils. A soil quality index (SQI) was
      developed based on the MDS method, whilst HPPS, MPPS and LPPS received mean SQI
      scores of 0.725, 0.536 and 0.425, respectively, with a ranking of HPPS > MPPS >
      LPPS. HPPS showed relatively good soil quality characterized by optimal nutrient
      availability, enzymatic and microbial activities, but the opposite was true of
      LPPS. Low levels of TN, AP and soil microbial activities were considered to be
      the major constraints limiting the productivity in LPPS. All soil samples
      collected were rich in available N, K, Si and Zn, but deficient in available P,
      which may be the major constraint for the studied regions. Managers in our study
      area should employ more appropriate management in the LPPS to improve its rice
      productivity, and particularly to any potential limiting factor. 

PMID- 25997108
TI  - Association between hypoglycaemia and impaired hypoglycaemia awareness and
      mortality in people with Type 1 diabetes mellitus.
AB  - AIMS: To examine whether severe hypoglycaemia and impaired hypoglycaemic
      awareness, a principal predictor of severe hypoglycaemia, are associated with all
      cause mortality or cardiovascular mortality in Type 1 diabetes mellitus. METHODS:
      Mortality was recorded in two cohorts, one in Denmark (n = 269, follow-up 12
      years) and one in the Netherlands (n = 482, follow-up 6.5 years). In both
      cohorts, awareness class was characterized and numbers of episodes of severe
      hypoglycaemia either during lifetime (Danish cohort) or during the preceding year
      (Dutch cohort) were recorded. In addition, episodes of severe hypoglycaemia were
      prospectively recorded every month for 1 year in the Danish cohort. Follow-up
      data regarding mortality were obtained through medical reports and registries
      (Danish cohort). RESULTS: All-cause mortality was 14% (n = 39) in the Danish and
      4% (n = 20) in the Dutch cohort. In either cohort, neither presence of episodes
      with severe hypoglycaemia nor impaired hypoglycaemia awareness were associated
      with increased mortality in age-truncated Cox proportional hazard regression
      models. Variables associated with increased risk of all-cause mortality in both
      cohorts were evidence of macrovascular disease and reduced kidney function.
      CONCLUSIONS: Severe hypoglycaemia and hypoglycaemia unawareness are not
      associated with increased risk of all-cause or cardiovascular mortality in people
      with Type 1 diabetes mellitus.

PMID- 25997109
TI  - Freshwater Ammonia-Oxidizing Archaea Retain amoA mRNA and 16S rRNA during Ammonia
      Starvation.
AB  - In their natural habitats, microorganisms are often exposed to periods of
      starvation if their substrates for energy generation or other nutrients are
      limiting. Many microorganisms have developed strategies to adapt to fluctuating
      nutrients and long-term starvation. In the environment, ammonia oxidizers have to
      compete with many different organisms for ammonium and are often exposed to long
      periods of ammonium starvation. We investigated the effect of ammonium starvation
      on ammonia-oxidizing archaea (AOA) and bacteria (AOB) enriched from freshwater
      lake sediments. Both AOA and AOB were able to recover even after almost two
      months of starvation; however, the recovery time differed. AOA and AOB retained
      their 16S rRNA (ribosomes) throughout the complete starvation period. The AOA
      retained also a small portion of the mRNA of the ammonia monooxygenase subunit A
      (amoA) for the complete starvation period. However, after 10 days, no amoA mRNA
      was detected anymore in the AOB. These results indicate that AOA and AOB are able
      to survive longer periods of starvation, but might utilize different strategies. 

PMID- 25997111
TI  - A calibration transmission method to determine the gamma-ray linear attenuation
      coefficient without a collimator.
AB  - It is shown that the gamma-ray linear attenuation coefficient of a sample with
      unknown chemical composition can be determined through a systematic calibration
      of the correlation between the linear attenuation coefficient, gamma-ray energy
      and the relative degree of attenuation. For calibration, H2O, MnO2, NaCl, Na2CO3
      and (NH4)2SO4 were used as reference materials. Point-like gamma-ray sources with
      modest activity of approximately 37kBq, along with an HPGe detector, were used in
      the measurements. A semi-empirical formula was derived to calculate the linear
      attenuation coefficients as a function of the relative count rate and the gamma
      ray energy. The method was applied to the determination of the linear attenuation
      coefficients for K2CrO4 and SiO2 test samples in the same setup used in
      calibration. The experimental result agreed well with the ones calculated by
      elementary data. 

PMID- 25997112
TI  - Two determinations of the (223)Ra half-life.
AB  - Ra-223 is an alpha-emitter that is being used as a bone-seeking radiotherapeutic
      agent. The relatively large uncertainty on its evaluated half-life (0.26%, Be et
      al., 2011) is an impediment to precision activity assays, which often involve
      measurements by various methods over time spans of days or weeks. We have
      performed two series of measurements using an ionization chamber (IC) and a
      NaI(Tl) well counter (gamma-wc) to determine new, precise values for the (223)Ra
      half-life. We have endeavored to realistically assess the uncertainties on the
      derived half-lives, looking beyond the fit uncertainties to identify uncertainty
      components acting on multiple timescales. We recovered respective values of
      11.447(6)d and 11.445(13)d from the IC and gamma-wc measurements. Our values are
      in accord with the evaluated value of 11.43(3)d, but with smaller combined
      uncertainties. 

PMID- 25997110
TI  - Horizontal gene transfer, dispersal and haloarchaeal speciation.
AB  - The Halobacteria are a well-studied archaeal class and numerous investigations
      are showing how their diversity is distributed amongst genomes and geographic
      locations. Evidence indicates that recombination between species continuously
      facilitates the arrival of new genes, and within species, it is frequent enough
      to spread acquired genes amongst all individuals in the population. To create
      permanent independent diversity and generate new species, barriers to
      recombination are probably required. The data support an interpretation that
      rates of evolution (e.g., horizontal gene transfer and mutation) are faster at
      creating geographically localized variation than dispersal and invasion are at
      homogenizing genetic differences between locations. Therefore, we suggest that
      recurrent episodes of dispersal followed by variable periods of endemism break
      the homogenizing forces of intrapopulation recombination and that this process
      might be the principal stimulus leading to divergence and speciation in
      Halobacteria.

PMID- 25997113
TI  - Label-free quantitative mass spectrometry for analysis of protein antigens in a
      meningococcal group B outer membrane vesicle vaccine.
AB  - The development of a multivalent outer membrane vesicle (OMV) vaccine where each
      strain contributes multiple key protein antigens presents numerous analytical
      challenges. One major difficulty is the ability to accurately and specifically
      quantitate each antigen, especially during early development and process
      optimization when immunoreagents are limited or unavailable. To overcome this
      problem, quantitative mass spectrometry methods can be used. In place of
      traditional mass assays such as enzyme-linked immunosorbent assays (ELISAs),
      quantitative LC-MS/MS using multiple reaction monitoring (MRM) can be used during
      early-phase process development to measure key protein components in complex
      vaccines in the absence of specific immunoreagents. Multiplexed, label-free
      quantitative mass spectrometry methods using protein extraction by either
      detergent or 2-phase solvent were developed to quantitate levels of several
      meningococcal serogroup B protein antigens in an OMV vaccine candidate. Precision
      was demonstrated to be less than 15% RSD for the 2-phase extraction and less than
      10% RSD for the detergent extraction method. Accuracy was 70 to 130% for the
      method using a 2-phase extraction and 90-110% for detergent extraction. The
      viability of MS-based protein quantification as a vaccine characterization method
      was demonstrated and advantages over traditional quantitative methods were
      evaluated. Implementation of these MS-based quantification methods can help to
      decrease the development time for complex vaccines and can provide orthogonal
      confirmation of results from existing antigen quantification techniques. 

PMID- 25997114
TI  - The effects of silver coating on friction coefficient and shear bond strength of
      steel orthodontic brackets.
AB  - Aims of the present study was to measure frictional resistance between silver
      coated brackets and different types of arch wires, and shear bond strength of
      these brackets to the tooth. In an experimental clinical research 28 orthodontic
      brackets (standard, 22 slots) were coated with silver ions using electroplate
      method. Six brackets (coated: 3, uncoated: 3) were evaluated with Scanning
      Electron Microscopy and Atomic Force Microscopy. The amount of friction in 15
      coated brackets was measured with three different kinds of arch wires (0.019 *
      0.025-in stainless steel [SS], 0.018-in stainless steel [SS], 0.018-in Nickel
      Titanium [Ni-Ti]) and compared with 15 uncoated steel brackets. In addition,
      shear bond strength values were compared between 10 brackets with silver coating
      and 10 regular brackets. Universal testing machine was used to measure shear bond
      strength and the amount of friction between the wires and brackets. SPSS 18 was
      used for data analysis with t-test. SEM and AFM results showed deposition of a
      uniform layer of silver, measuring 8-10 MUm in thickness on bracket surfaces.
      Silver coating led to higher frictional forces in all the three types of arch
      wires, which was statistically significant in 0.019 * 0.025-in SS and 0.018-in Ni
      Ti, but it did not change the shear bond strength significantly. Silver coating
      with electroplating method did not affect the bond strength of the bracket to
      enamel; in addition, it was not an effective method for decreasing friction in
      sliding mechanics.

PMID- 25997115
TI  - The Safety and Efficacy of PF-04958242 in Age-Related Sensorineural Hearing Loss:
      A Randomized Clinical Trial.
AB  - IMPORTANCE: To our knowledge, this is the first study to assess the potential to
      pharmacologically improve auditory function in adults with age-related
      sensorineural hearing loss. OBJECTIVE: To explore the potential for the alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid potentiator mechanism to
      affect auditory function in individuals with mild to moderate age-related
      sensorineural hearing loss. DESIGN, SETTING, AND PARTICIPANTS: A randomized,
      double-blind, placebo-controlled, single-dose, 3-way crossover study was
      conducted in 3 academic ear, nose, and throat clinics and 2 private clinical
      research centers between December 22, 2011, and February 26, 2013. Participants
      were 50- to 75-year-old men and women of nonchildbearing potential with mild to
      moderate sensorineural hearing loss. INTERVENTIONS: Three single doses of PF
      04958242, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate
      positive allosteric modulator, and placebo. MAIN OUTCOMES AND MEASURES: Pure-tone
      average, speech discrimination score, and speech in noise testing change from
      baseline at 1 and 5 hours after a single dose of PF-04958242. RESULTS: The
      treatment was safe and well tolerated. The estimates for the primary end point
      change from baseline in pure-tone average compared with placebo at 1 hour were 
      0.77 (95% CI, -2.14 to 0.59) and 0.37 (95% CI, -0.97 to 1.72) for 0.27 and 0.35
      mg, respectively. At 5 hours the estimates were -0.57 (95% CI, -2.43 to 1.29) and
      -0.56 (95% CI, -2.45 to 1.33) for 0.27 and 0.35 mg, respectively. No significant
      change from baseline was demonstrated compared with placebo in the primary or
      secondary study end points at 1 or 5 hours after receiving treatment. CONCLUSIONS
      AND RELEVANCE: To our knowledge, this clinical trial is the first study of a
      pharmacologic treatment for age-related sensorineural hearing loss and provides
      information with regard to study design, end points, variability, data
      characteristics, and operational feasibility to guide the design of future
      hearing loss trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01518920.

PMID- 25997119
TI  - Fast size-determination of intact bacterial plasmids using nanofluidic channels.
AB  - We demonstrate how nanofluidic channels can be used as a tool to rapidly
      determine the number and sizes of plasmids in bacterial isolates. Each step can
      be automated at low cost, opening up opportunities for general use in
      microbiology labs. 

PMID- 25997120
TI  - Systemic treatment of vulvar cancer.
AB  - Squamous cell carcinoma of the vulva is a rare disease, accounting for
      approximately 5% of cancers of the female genital tract. Standard therapy for
      early-stage vulvar cancer mainly comprises of surgery of the vulva and groins. In
      locally advanced or metastatic vulvar cancer, neoadjuvant or definitive
      chemoradiation is often considered as an alternative treatment option. Given its
      rarity, the level of evidence for different treatment modalities is poor and few
      clinical trials have been performed on this disease. Therefore indication
      criteria for systemic treatment in advanced stage vulvar cancer vary widely among
      countries and institutions. This review focuses on the different systemic
      treatment options for patients with locally advanced, recurrent or metastatic
      vulvar cancer, and highlights the need for an international multicenter approach
      to identify the most effective therapeutic options. 

PMID- 25997124
TI  - High-speed roll-to-roll manufacturing of graphene using a concentric tube CVD
      reactor.
AB  - We present the design of a concentric tube (CT) reactor for roll-to-roll chemical
      vapor deposition (CVD) on flexible substrates, and its application to continuous
      production of graphene on copper foil. In the CTCVD reactor, the thin foil
      substrate is helically wrapped around the inner tube, and translates through the
      gap between the concentric tubes. We use a bench-scale prototype machine to
      synthesize graphene on copper substrates at translation speeds varying from 25
      mm/min to 500 mm/min, and investigate the influence of process parameters on the
      uniformity and coverage of graphene on a continuously moving foil. At lower
      speeds, high-quality monolayer graphene is formed; at higher speeds, rapid
      nucleation of small graphene domains is observed, yet coalescence is prevented by
      the limited residence time in the CTCVD system. We show that a smooth isothermal
      transition between the reducing and carbon-containing atmospheres, enabled by
      injection of the carbon feedstock via radial holes in the inner tube, is
      essential to high-quality roll-to-roll graphene CVD. We discuss how the foil
      quality and microstructure limit the uniformity of graphene over macroscopic
      dimensions. We conclude by discussing means of scaling and reconfiguring the
      CTCVD design based on general requirements for 2-D materials manufacturing.

PMID- 25997125
TI  - Bis(phenolate)amine-supported lanthanide borohydride complexes for styrene and
      trans-1,4-isoprene (co-)polymerisations.
AB  - New bis(phenolate)amine-supported neodymium borohydride complexes and their
      previously reported samarium analogues were tested as catalysts for the
      polymerisation of styrene and isoprene. Reaction of Na2O2N(L) (L = py, OMe, NMe2)
      with Nd(BH4)3(THF)3 afforded the borohydride complexes Nd(O2N(L))(BH4)(THF) (L =
      py (1-Nd), OMe (2-Nd), NMe2 (3-Nd)). Complex 1-Nd has shown a propensity to form
      phenolate-O-bridged dimer [Nd(MU-O2N(py))(BH4)]2 (1'-Nd) as previously observed
      with the samarium analogues Sm(O2N(L))(BH4)(THF) (L = py or Pr). X-ray structures
      of 1'-Nd and 2-Nd were determined and are presented. The neodymium borohydride
      complexes 1-Nd to 3-Nd and their samarium analogues Sm(O2N(L))(BH4)(THF)x (L = py
      (1-Sm), OMe (2-Sm), NMe2 (3-Sm), Pr (4-Sm)) were tested as catalysts for the
      polymerisation of isoprene and styrene in the presence of n-butylethylmagnesium
      (Mg((n)Bu)(Et)). All complexes were found to be active for the polymerisation of
      isoprene in these conditions, leading to polyisoprene up to 95.1% trans-1,4
      stereoregular. They were also found to be active for the polymerisation of
      styrene leading to atactic polystyrene in all cases. Interestingly, samarium
      based complexes were found to be more active than the neodymium ones toward this
      latter monomer, in sharp contrast to what is usually observed with rare earth
      borohydride complexes. The structure of both trans-polyisoprenes and polystyrenes
      obtained were studied in detail by MALDI-ToF analysis in order to better
      understand the polymerisation mechanisms. The coordinative chain transfer
      polymerisation (CCTP) of both monomers was further conducted using Mg((n)Bu)(Et)
      as transfer agent. Finally, the statistical copolymerisation of isoprene and
      styrene was examined using these catalytic systems, leading to the formation of
      poly[(trans-1,4-isoprene)-co-styrene] with up to 39% of styrene moieties inserted
      in a highly trans-1,4-stereoregular polyisoprene.

PMID- 25997126
TI  - Therapeutic efficacy of biochanin A against arsenic-induced renal and cardiac
      damage in rats.
AB  - The present study was investigated the effects of biochanin A (BCA) on arsenic
      toxicity in rats. For this purpose, rats were orally treated with arsenic in the
      form of sodium meta-arsenite alone (10mg/kg body weight (bw)/day) and co
      administered selenium (10mg/kgbw/day) and BCA at different doses (10, 20 and
      40mg/kgbw/day) for 6 weeks. Arsenic altered the oxidative stress indices in both
      renal and cardiac tissues. There was an increase in plasma renal markers,
      triglyceride, lipoproteins with no alterations in cholesterol levels were noted
      in arsenic-intoxicated rats. Non-significant changes of phospholipids and free
      fatty acids levels in the tissues of arsenic-exposed rats. The biochemical
      disturbances were well correlated with the histological findings in the kidney,
      but not in the heart. The administration of BCA and selenium significantly
      reversed the alterations in the above-mentioned parameters in arsenic-intoxicated
      rats. Our findings revealed the beneficial effects of BCA against arsenic
      toxicity. 

PMID- 25997127
TI  - Structure-Activity Relationship and Mode of Action of a Frog Secreted
      Antibacterial Peptide B1CTcu5 Using Synthetically and Modularly Modified or
      Deleted (SMMD) Peptides.
AB  - All life forms are equipped with rapidly acting, evolutionally conserved
      components of an innate immune defense system that consists of a group of unique
      and diverse molecules known as host defense peptides (HDPs). A Systematic and
      Modular Modification and Deletion (SMMD) approach was followed to analyse the
      structural requirement of B1CTcu5, a brevinin antibacterial peptide amide
      identified from the skin secretion of frog Clinotarsus curtipes, India, to show
      antibacterial activity and to explore the active core region. Seventeen SMMD
      B1CTcu5 analogs were designed and synthesised by C and N-terminal amino acid
      substitution or deletion. Enhancement in cationicity by N-terminal Lys/Arg
      substitution or hydrophobicity by Trp substitution produced no drastic change in
      bactericidal nature against selected bacterial strains except S. aureus. But the
      sequential removal of N-terminal amino acids had a negative effect on
      bactericidal potency. Analog B1CTcu5-LIAG obtained by the removal of four N
      terminal amino acids displayed bactericidal effect comparable to, or in excess
      of, the parent peptide with reduced hemolytic character. Its higher activity was
      well correlated with the improved inner membrane permeabilisation capacity. This
      region may act as the active core of B1CTcu5. Presence of C-terminal disulphide
      bond was not a necessary condition to display antibacterial activity but helped
      to promote hemolytic nature. Removal of the C-terminal rana box region
      drastically reduced antibacterial and hemolytic activity of the peptide, showing
      that this region is important for membrane targeting. The bactericidal potency of
      the D-peptide (DB1CTcu5) helped to rule out the stereospecific interaction with
      the bacterial membrane. Our data suggests that both the C and N-terminal regions
      are necessary for bactericidal activity, even though the active core region is
      located near the N-terminal of B1CTcu5. A judicious modification at the N
      terminal region may produce a short SMMD analog with enhanced bactericidal
      activity and low toxicity against eukaryotic cells. 

PMID- 25997128
TI  - Science to Practice: Monitoring Oncolytic Virus Therapy with Chemical Exchange
      Saturation Transfer MR Imaging--Wishful Thinking?
AB  - Farrar et al demonstrate that modifying an oncolytic virus (OV) so that it
      produces excess protein when it infects a cancer cell is a process that can be
      detected both in vitro and in vivo in infected cancer cells by using chemical
      exchange saturation transfer (CEST) magnetic resonance (MR) imaging. The effect
      is at the limits of MR imaging detection (approximately 1%), but experience with
      functional MR imaging of the brain, with comparably small effects, should give
      pause to anyone who immediately writes this observation off as an exercise in
      wishful thinking. OVs are improving in their specificity, virulence, and ability
      to induce immune responses. Now, they have been modified to express proteins that
      are detectable with CEST MR imaging early after delivery into a tumor. This is
      clearly a surprising and hopeful development in the long road of OVs from the
      laboratory to the clinic.

PMID- 25997129
TI  - CT Scanning: Is the Contrast Material Enhancing the Radiation Dose and Cancer
      Risk as Well as the Image?

PMID- 25997130
TI  - Elbow US: Anatomy, Variants, and Scanning Technique.
AB  - As with other musculoskeletal joints, elbow ultrasonography (US) depends on the
      examination technique. Deep knowledge of the relevant anatomy, such as the bone
      surface anatomy, tendon orientation, nerves, and vessels, is crucial for
      diagnosis. It is important to be aware of the primary imaging pitfalls related to
      US technique (anisotropy) in the evaluation of deep tendons such as the distal
      biceps and peripheral nerves. In this article, US scanning technique for the
      elbow as well as the related anatomy, primary variants, and scanning pitfalls are
      described. In addition, an online video tutorial of elbow US describes a possible
      approach to elbow evaluation. Online supplemental material is available for this
      article.

PMID- 25997131
TI  - Large-Bowel Obstruction in the Adult: Classic Radiographic and CT Findings,
      Etiology, and Mimics.
AB  - Large-bowel obstruction is an abdominal emergency with high morbidity and
      mortality rates if left untreated. Although abdominal radiography is usually the
      initial imaging study performed in patients suspected of having large-bowel
      obstruction, it may not be sufficient to distinguish obstruction from other
      causes of colonic dilatation. Computed tomography is the imaging method of choice
      as it can establish the diagnosis and cause of large-bowel obstruction. A
      contrast agent enema may be used to confirm or exclude large-bowel obstruction.
      In this review, the imaging findings in multiple causes of large-bowel
      obstruction are illustrated and compared with acute colonic pseudo-obstruction.

PMID- 25997135
TI  - Case 218: Birt-Hogg-Dube syndrome.
AB  - History A 53-year-old man presented to the emergency department with subacute
      poorly localized abdominal pain that was increasing in intensity. He had a
      history of spontaneous pneumothoraces and skin lesion biopsy. Clinical
      examination revealed numerous small dome-shaped flesh-colored papules on the head
      and neck, as well as multiple palpable soft pliable nontender subcutaneous tumors
      scattered over the chest, abdomen, and extremities. Laboratory test results were
      unremarkable. The patient underwent contrast material-enhanced multidetector
      computed tomography (CT) of the chest, abdomen, and pelvis after intravenous
      administration of 120 mL of iohexol (Omnipaque 350; GE Healthcare, Princeton, NJ)
      infused at a rate of 3 mL/sec. 

PMID- 25997136
TI  - Contrast Material-induced Nephropathy: Causation Quandaries.

PMID- 25997137
TI  - Perplexing histologic classification of thymic epithelial tumor.

PMID- 25997138
TI  - Intravenous contrast material and acute kidney injury: a need for caution.

PMID- 25997139
TI  - Review articles.

PMID- 25997140
TI  - Tracheomalacia in Adults with Cystic Fibrosis: Determination of Prevalence and
      Severity with Dynamic Cine CT.

PMID- 25997141
TI  - Iodinated contrast media: a semantic somersault.

PMID- 25997142
TI  - Herniated Lumbar Disks: Real-time MR Imaging Evaluation during Continuous
      Traction.

PMID- 25997146
TI  - Performance of manual ventilation: how to define its efficiency in bench studies?
      A review of the literature.
AB  - Bench studies have become the preferred way to evaluate the performance of airway
      equipment, since clinical trials are not specifically required before marketing
      these devices. However, it is difficult to assess the efficiency of ventilation
      without recording physiological data. This review analyses how efficiency of
      manual ventilation has been defined in recent studies, and how their results may
      be affected. We searched electronic databases from 2000 to April 2014. The main
      inclusion criterion was the analysis of performance of ventilation. Nine relevant
      articles were selected from 53 eligible publications. Most studies used the same
      parameters; tidal volume and ventilation rate. However, there were significant
      differences between the definitions of performance of ventilation, both in terms
      of criteria of judgement and methods of analysis. None of these approaches is
      able to provide a clear understanding of variability of ventilation during a
      given period. A new definition may increase the relevance of bench studies to
      clinical medicine, by more appropriately assessing the performance of
      ventilation. 

PMID- 25997147
TI  - A high ratio of IC31((r)) adjuvant to antigen is necessary for H4 TB vaccine
      immunomodulation.
AB  - A tuberculosis (TB) vaccine consisting of a recombinant fusion protein (H4) and a
      novel TLR9 adjuvant (IC31) is in clinical development. To better understand the
      H4-IC31 ratio, we measured the binding capacity of IC31 for H4 protein and
      immunized mice with formulations that contained limiting to excess ratios of IC31
      to H4. An immunomodulated H4-specific IFNgamma response was only observed when
      IC31 was present in excess of H4. Since TLR expression is species-specific and
      the vaccine is intended to boost BCG-primed immunity, we questioned whether data
      in mice would translate to humans. To address this question, we used the fresh
      human Whole Blood (hWB) recovered from BCG-vaccinated subjects to screen H4-IC31
      formulations. We found IC31 modulation in hWB to be quite distinct from the TLR4
      Adjuvant. Unlike TLR4-Adjuvant, IC31 formulations did not induce the pro
      inflammatory cytokine TNFalpha, but modulated a robust H4-specific IFNgamma
      response after 12 d of culture. We then re-stimulated the fresh hWB of 5 BCG
      primed subjects with formulations that had excess or limiting IC31 binding for H4
      protein and again found that an immunomodulated H4-specific IFNgamma response
      needed an excess of IC31. Finally, we monitored the zeta (zeta) potential of H4
      IC31 formulations and found that the overall charge of H4-IC31 particles changes
      from negative to positive once IC31 is in greater than 9-fold excess. Using two
      diverse yet mutually supportive approaches, we confirm the need for an excess of
      IC31 adjuvant in H4 TB vaccine formulations and suggest surface potential may be
      an important factor. 

PMID- 25997148
TI  - Academic Outcome Measures of a Dedicated Education Unit Over Time: Help or
      Hinder?
AB  - Critical thinking, nursing process, quality and safety measures, and standardized
      RN exit examination scores were compared between students (n = 144) placed in a
      dedicated education unit (DEU) and those in a traditional clinical model.
      Standardized test scores showed that differences between the clinical groups were
      not statistically significant. This study shows that the DEU model is 1 approach
      to clinical education that can enhance students' academic outcomes. 

PMID- 25997149
TI  - Teaching Strategies to Increase Cultural Awareness in Nursing Students.
AB  - Cultural competence education is essential for all nurses to better prepare them
      to address the underlying social environment of patients, families, and
      communities. This article describes a study with second degree nursing students
      that tested 6 teaching strategies for their effectiveness in raising cultural
      awareness, a key aspect of cultural competence. The results demonstrated that the
      interventions had a positive effect. 

PMID- 25997150
TI  - Introducing Information Literacy Competency Standards for Nursing.
AB  - The Association for College and Research Libraries published the Information
      Literacy Competency Standards for Nursing (ILCSN) in January 2014, written by a
      task force of the Health Sciences Interest Group of the American Library
      Association. The ILCSN describes skills ranging from basic to advanced
      information research competencies for students enrolled in nursing programs at
      all levels and for professional nurses. This article guides administrators and
      faculty in use of the standards to design programs and coursework in information
      skills to support evidence-based practice. 

PMID- 25997151
TI  - Nursing Students' Willingness to Care for Human Immunodeficiency Virus-Infected
      Patients in the Future.
AB  - Recent studies in various countries have shown controversy regarding students'
      willingness to care for human immunodeficiency virus (HIV)-infected patients as
      well as factors associated with students' decisions about this issue. This
      survey, based on the Theory of Planned Behavior, explored factors associated with
      Israeli nursing students' willingness to care for HIV-infected patients in the
      future. The results suggest that appropriate education and experience in caring
      for HIV-infected patients are critical for improving students' willingness to
      care for these patients. 

PMID- 25997152
TI  - Predatory Publishing: What You Don't Know Can Hurt You.

PMID- 25997153
TI  - Leveraging Quality and Safety Education for Nurses to Enhance Graduate-Level
      Nursing Education and Practice.
AB  - The purpose of this article is to provide information about the efforts to
      educate faculty teaching in graduate programs about the Quality and Safety
      Education for Nurses (QSEN) competencies, provide examples of teaching strategies
      for each graduate competency, and finally provide information about the outcomes
      of the graduate-faculty QSEN project. Examples are given of the critical QSEN
      work that remains to be done to ensure that care for patients and communities is
      high quality, safe, and reliable. 

PMID- 25997154
TI  - Service Learning With a Geriatric Population: Changing Attitudes and Improving
      Knowledge.
AB  - Relatively few nursing students choose to specialize in geriatric nursing. While
      increased clinical exposure and improved knowledge of the elderly have been
      proposed to manage this staffing dilemma, successful strategies have not been
      identified. This study examined nursing students' attitudes and knowledge about
      the elderly, before and after service learning experiences in Senior Citizen
      Centers. Through these interventions, students had significantly improved
      attitudes and knowledge about the elderly. 

PMID- 25997155
TI  - Neuropsychological Function in a Case of Dandy-Walker Variant in a 68-Year-Old
      Veteran.
AB  - Dandy-Walker syndrome (DWS) is a congenital brain malformation that is
      characterized by partial or complete agenesis of the cerebellar vermis and cystic
      dilatation of the 4th ventricle that shifts ventrolaterally to displace the
      cerebellar hemispheres. This case is a 68-year-old male veteran with complaints
      of new-onset cognitive disorder who was found to have previously unsuspected DWS
      on head computed tomography. This is one of the first case studies to present
      complete neuropsychological test results in a veteran with DWS. Despite the level
      of abnormality on imaging, the veteran functioned well until onset of mild
      cognitive impairments in late adulthood. 

PMID- 25997156
TI  - High levels of interspecific gene flow in an endemic cichlid fish adaptive
      radiation from an extreme lake environment.
AB  - Studying recent adaptive radiations in isolated insular systems avoids
      complicating causal events and thus may offer clearer insight into mechanisms
      generating biological diversity. Here, we investigate evolutionary relationships
      and genomic differentiation within the recent radiation of Alcolapia cichlid fish
      that exhibit extensive phenotypic diversification, and which are confined to the
      extreme soda lakes Magadi and Natron in East Africa. We generated an extensive
      RAD data set of 96 individuals from multiple sampling sites and found evidence
      for genetic admixture between species within Lake Natron, with the highest levels
      of admixture between sympatric populations of the most recently diverged species.
      Despite considerable environmental separation, populations within Lake Natron do
      not exhibit isolation by distance, indicating panmixia within the lake, although
      individuals within lineages clustered by population in phylogenomic analysis. Our
      results indicate exceptionally low genetic differentiation across the radiation
      despite considerable phenotypic trophic variation, supporting previous findings
      from smaller data sets; however, with the increased power of densely sampled
      SNPs, we identify genomic peaks of differentiation (FST outliers) between
      Alcolapia species. While evidence of ongoing gene flow and interspecies
      hybridization in certain populations suggests that Alcolapia species are
      incompletely reproductively isolated, the identification of outlier SNPs under
      diversifying selection indicates the radiation is undergoing adaptive divergence.

PMID- 25997158
TI  - A Lithium Amide Protected Against Protonation in the Gas Phase: Unexpected Effect
      of LiCl.
AB  - In cold THF and in the presence of LiCl, a lithium pyrrolidinylamide forms a 1:1
      mixed aggregate, which is observed directly by ESI-MS. Gas-phase protonation of
      this species leads to selective transfer of H(+) to the chlorine, suggesting that
      LiCl shields the amide nitrogen and prevents its direct protonation. 

PMID- 25997157
TI  - Comparative transcriptomic analysis of multiple cardiovascular fates from
      embryonic stem cells predicts novel regulators in human cardiogenesis.
AB  - Dissecting the gene expression programs which control the early stage
      cardiovascular development is essential for understanding the molecular
      mechanisms of human heart development and heart disease. Here, we performed
      transcriptome sequencing (RNA-seq) of highly purified human Embryonic Stem Cells
      (hESCs), hESC-derived Multipotential Cardiovascular Progenitors (MCPs) and MCP
      specified three cardiovascular lineages. A novel algorithm, named as Gene
      Expression Pattern Analyzer (GEPA), was developed to obtain a refined lineage
      specificity map of all sequenced genes, which reveals dynamic changes of
      transcriptional factor networks underlying early human cardiovascular
      development. Moreover, our GEPA predictions captured ~90% of top-ranked
      regulatory cardiac genes that were previously predicted based on chromatin
      signature changes in hESCs, and further defined their cardiovascular lineage
      specificities, indicating that our multi-fate comparison analysis could predict
      novel regulatory genes. Furthermore, GEPA analysis revealed the MCP-specific
      expressions of genes in ephrin signaling pathway, positive role of which in
      cardiomyocyte differentiation was further validated experimentally. By using RNA
      seq plus GEPA workflow, we also identified stage-specific RNA splicing switch and
      lineage-enriched long non-coding RNAs during human cardiovascular
      differentiation. Overall, our study utilized multi-cell-fate transcriptomic
      comparison analysis to establish a lineage-specific gene expression map for
      predicting and validating novel regulatory mechanisms underlying early human
      cardiovascular development. 

PMID- 25997159
TI  - Novel FLG null mutations in Korean patients with atopic dermatitis and comparison
      of the mutational spectra in Asian populations.
AB  - Filaggrin is essential for the development of the skin barrier. Mutations in the
      gene encoding filaggrin have been identified as major predisposing factors for
      atopic disorders. Molecular analysis of the FLG gene in this study showed nine
      null and one unclassified mutation in 13 of 81 Korean patients with atopic
      dermatitis (AD): five novel null mutations (i.e. p.S1405*, c.5671_5672delinsTA,
      p.W1947*, p.G2025* and p.E3070*); four reported null mutations (i.e. c.3321delA,
      p.S1515*, p.S3296* and p.K4022*); and one unclassified mutation (i.e.
      c.306delAAAGCACAG). These variants are nonsense, premature termination codon or
      in-frame deletion expected to cause loss-of-function of FLG. Genotype-phenotype
      correlation is not obvious in Korean AD patients with FLG null mutations.
      According to a review of the mutational spectra of the FLG gene in the Asian
      populations, FLG null mutations appeared to be unique in each population but some
      mutations such as p.R501*, c.3321delA, p.S1515*, p.S3296* and p.K4022* were
      commonly found in at least two of the selected Asian populations including
      Korean, Japanese, Chinese, Singaporean Chinese or Taiwanese. Further
      investigations on a larger group of Korean AD would be necessary to elucidate its
      clinical pathogenesis and mutational spectrum related to specific FLG null
      mutations for AD. 

PMID- 25997160
TI  - Metal extent in blood of livestock from Dandora dumping site, Kenya: Source
      identification of Pb exposure by stable isotope analysis.
AB  - Nairobi city in Kenya produces 2000 tons/day of garbage, and most of it is dumped
      onto the Dandora dumping site, home to a quarter-million residents. This study
      was conducted (1) to assess the contamination levels of nine metals and a
      metalloid (arsenic) in the blood of pigs, goats, sheep and cattle from Dandora,
      and (2) to identify a possible source of lead (Pb) pollution. Cadmium (Cd, 0.17
      4.35 MUg/kg, dry-wt) and Pb (90-2710 MUg/kg) levels in blood were generally high,
      suggesting human exposure to Cd through livestock consumption and Pb poisoning
      among pigs (2600 MUg/kg) and cattle (354 MUg/kg). Results of Pb isotope ratios
      indicated that the major exposure route might differ among species. Our results
      also suggested a possibility that the residents in Dandora have been exposed to
      the metals through livestock consumption.

PMID- 25997161
TI  - Liver-FibroSTARD checklist and glossary: tools for standardized design and
      reporting of diagnostic accuracy studies of liver fibrosis tests.

PMID- 25997162
TI  - Mechanical nociceptive thresholds using four probe configurations in horses.
AB  - OBJECTIVE: To examine the relationship between probe tip size and force readings
      of mechanical nociceptive thresholds (MTs) to identify appropriate probes for
      horses. STUDY DESIGN: Randomized, crossover study. ANIMALS: Eight adult, mixed
      breed horses aged 5-10 years, weighing 268-460 kg. METHODS: Four probe
      configurations (PCs) were used in random sequence: 1.0 mm diameter (SHARP); 3.2
      mm (BLUNT); spring-mounted 1.0 mm (SPRING), and 3 * 2.5 mm (3PIN). A remote
      controlled unit on the horse increased force (1.2 N second(-1)) in a pneumatic
      actuator on the metacarpus. Mean MT for each PC was calculated from 10 readings
      for each horse. Data were log-transformed for analysis using mixed-effects
      anova/linear regression (p < 0.05). Variability of data for each PC was assessed
      using the coefficient of variation (CV). RESULTS: Mean +/- standard deviation MTs
      were: SHARP, 5.6 +/- 2.3 N; BLUNT, 11.4 +/- 3.4 N; 3PIN, 9.6 +/- 4.6 N, and
      SPRING 6.4 +/- 1.8 N. Mean MT for SHARP was significantly lower than for BLUNT (p
      < 0.001) and 3PIN (p < 0.001), but not different from SPRING (p > 0.05). Mean MT
      was significantly higher for BLUNT than for 3PIN (p < 0.05) and SPRING (p <
      0.001). Mean MT for 3PIN was significantly higher than for SPRING (p < 0.001).
      Larger contact area PCs produced higher MTs than smaller PCs, but the
      relationship was not linear. BLUNT (area: 10-fold greater) gave a MT two-fold
      higher than SHARP. 3PIN (area: 20-fold greater) produced more variable MTs, less
      than two-fold higher than SHARP. SPRING was similar to SHARP. CVs were: SHARP,
      22.9%; BLUNT, 72.3%; 3PIN, 44.2%, and SPRING, 28.7%. CONCLUSIONS AND CLINICAL
      RELEVANCE: The PC has nonlinear effects on MT. Therefore, it is important to
      define PC when measuring MT. Smaller probe tips may be preferable as MT data are
      less variable.

PMID- 25997163
TI  - You've got mail (and an STI).

PMID- 25997166
TI  - Stopping long-acting beta2-agonists (LABA) for children with asthma well
      controlled on LABA and inhaled corticosteroids.
AB  - BACKGROUND: Asthma is the most common chronic medical condition among children
      and is one of the most common causes of hospitalisation and medical visits.
      Poorly controlled asthma often leads to preventable exacerbations that require
      additional medications, hospital stays, or treatment in the emergency
      department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment
      for children with asthma whose symptoms are not well controlled on inhaled
      corticosteroids (ICS). The US Food and Drug Administration has issued a 'black
      box' warning for LABA in asthma, and now recommends that they be used "for the
      shortest duration of time required to achieve control of asthma symptoms and
      discontinued, if possible, once asthma control is achieved". OBJECTIVES: To
      compare the effect on asthma control and adverse effects of stepping down to
      inhaled corticosteroids (ICS)-only therapy versus continuing ICS plus LABA in
      children whose asthma is well controlled on combined ICS and LABA therapy. SEARCH
      METHODS: We searched the Cochrane Airways Group Specialised Register, and also
      searched www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of
      primary studies and existing reviews, and manufacturers' trial registries
      (GlaxoSmithKline and AstraZeneca). We searched all databases from their inception
      to the present, and imposed no restriction on language of publication. The most
      recent search was done in April 2015. SELECTION CRITERIA: We looked for parallel
      randomised controlled trials of at least eight weeks' duration, available as
      published full text, abstract only, or unpublished data. We excluded studies
      including participants with other chronic respiratory comorbidities (for example
      bronchiectasis).We looked for studies in which children (18 years or younger)
      whose asthma was well controlled on any dose of ICS and LABA combination therapy
      were randomised to: a) step-down therapy to ICS alone or b) continued use of ICS
      and LABA.We included any dose of LABA (formoterol, salmeterol, vilanterol) and
      any dose of ICS (beclomethasone, budesonide, ciclesonide, mometasone,
      flunisolide, fluticasone propionate, fluticasone furoate, triamcinolone)
      delivered in a combination inhaler or in separate inhalers. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened all records identified in the
      searches. We used a data extraction tool in Microsoft Excel to manage searches
      and document reasons for inclusion and exclusion, and to extract descriptive and
      numerical data from trials meeting the inclusion criteria.The prespecified
      primary outcomes were exacerbations requiring oral steroids, asthma control, and
      all-cause serious adverse events. MAIN RESULTS: Despite conducting extensive
      searches of electronic databases, trial registries and manufacturers' websites we
      identified no trials matching the inclusion criteria.After removing duplicates,
      we screened 1031 abstracts, and assessed 43 full-text articles for inclusion. We
      identified several adult studies, which will be summarised in a separate review
      (Ahmad 2014). The most common reasons for exclusion after viewing full texts were
      'wrong comparison' (n = 22) and 'adult population' (n = 18).Some adult studies
      recruited adolescents from age 15, but none reported data separately for those
      under 18. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised
      trials to inform the discontinuation of LABAs in children once asthma control is
      achieved with ICS plus LABA. It is disappointing that such an important issue has
      not been studied, and a randomised double-blind trial recruiting children who are
      controlled on ICS plus LABA is warranted. The study should be large enough to
      assess children of different ages, and to measure the important safety and
      efficacy outcomes suggested in this review over at least six months.The only
      randomised evidence for stopping LABA has been conducted in adults; it will be
      summarised in a separate review.

PMID- 25997165
TI  - Distance and Interference in the Reference Management of African American Adults.
AB  - PURPOSE: The purpose of this study was to examine the effect of distance and
      interference on the adequacy of reference management in 2 contrasting narrative
      conditions among age-defined groups of healthy African American adults. METHODS:
      Twenty middle-aged (M = 51 years) and 20 older (M = 72 years) women produced a
      complex story retelling and a personal narrative of a childhood experience. All
      narratives were transcribed orthographically, parsed into terminal units (T
      units), and analyzed for surface structure markings of referents. RESULTS:
      Results varied on the basis of task complexity and specific dependent variables.
      Older adults produced shorter T-unit distances between nouns and pronouns in
      story retelling compared with middle-aged adults. Middle-aged adults, but not
      older adults, exhibited longer T-unit distances between referents on story
      retelling than on personal narratives. Both groups performed similarly in the
      management of intervening information between referents. The presence of African
      American English features was related to interference but not to referential
      distance. CONCLUSIONS: Older adults demonstrated an effective age-related
      strategy for simplifying complex story retelling by producing shorter T-unit
      distances and, thus, less intervening information between referents. These
      findings suggest that referential distance may be a more important factor in
      mediating story recall. (For a summary and guidelines for therapy, see Bunce,
      1991.).

PMID- 25997167
TI  - Pattern extraction for high-risk accidents in the construction industry: a data
      mining approach.
AB  - Accidents involving falls and falling objects (group I) are highly frequent
      accidents in the construction industry. While being hit by a vehicle, electric
      shock, collapse in the excavation and fire or explosion accidents (group II) are
      much less frequent, they make up a considerable proportion of severe accidents.
      In this study, multiple-correspondence analysis, decision tree, ensembles of
      decision tree and association rules methods are employed to analyse a database of
      construction accidents throughout Iran between 2007 and 2011. The findings
      indicate that in group I, there is a significant correspondence among these
      variables: time of accident, place of accident, body part affected, final
      consequence of accident and lost workdays. Moreover, the frequency of accidents
      in the night shift is less than others, and the frequency of injury to the head,
      back, spine and limbs are more. In group II, the variables time of accident and
      body part affected are mostly related and the frequency of accidents among
      married and older workers is more than single and young workers. There was a
      higher frequency in the evening, night shifts and weekends. The results of this
      study are totally in line with the previous research. 

PMID- 25997169
TI  - Predictors of admission and readmission to hospital for major depression: A
      community cohort study of 52,990 individuals.
AB  - BACKGROUND: Our current knowledge about predictors of admission and re-admission
      to hospital as a result of major depressive disorder (MDD) is limited. Here we
      present a descriptive analysis of factors which are associated with MDD
      hospitalisations within a large population cohort. METHODS: We linked
      participants of the Scottish Health Survey (SHS) to historical and prospective
      hospital admission data. We combined information from the SHS baseline interview
      and historical hospitalisations to define a range of exposure variables. The main
      outcomes of interest were: (1) first time admission for MDD occurring after the
      SHS interview; and (2) readmission for MDD. We used Cox regression to determine
      the association between each predictor and each outcome, after adjusting for age,
      gender and deprivation quintile. RESULTS: 52,990 adult SHS participants were
      included. During a median follow-up of 4.5 years per participant, we observed 530
      first-time admissions for MDD. A relatively wide range of factors - encompassing
      social, individual health status, and lifestyle-related exposures - were
      associated with this outcome (p<0.05). Among the 530 participants exhibiting a de
      novo admission for MDD during follow-up, 118 were later re-admitted. Only older
      age (over 70) and a prior non-depression related psychiatric admission were
      associated with readmission for MDD. LIMTATIONS: MDD was defined using records of
      International Classification of Disease hospital discharge codes rather than
      formal diagnostic assessments. CONCLUSION: These findings have implications for
      mental health service organisation and delivery and should stimulate future
      research on predictive factors for admission and readmission in MDD.

PMID- 25997168
TI  - In situ coronary stent paving by Pluronic F127-alginate gel blends: Formulation
      and erosion tests.
AB  - In this work the development of an experimental protocol to perform the in situ
      gel-paving of coronary stent is presented. Biocompatible aqueous blends of
      Pluronic F127 and sodium alginates are used as potential drug dosage system for
      pharmacological in situ treatment of coronary in-stent restenosis. Pluronic
      F127/alginate aqueous blend has the unique characteristic to be liquid at room
      condition and to form gel at physiological temperature. The proposed protocol is
      based on the blend injection on stent wall previously implanted in a flexible
      silicon pipe mimicking the coronary artery. Injected blend is warmed up until
      human body temperature achieving a soft gel, then it is reticulated by copper
      bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion
      phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device,
      (the Simulated Artery Device, SAD), was built to simulate the human circulatory
      apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4)
      was fluxed by a peristaltic pump through the pipe hosting the covered stent.
      Erosion tests were performed monitoring, by gravimetric and spectrophotometric
      methods, the residual mass anchored to stent mesh after given times. The obtained
      results showed that the in situ gel-paving developed protocol was efficacious and
      reliable. The gel-paving was completely eroded in a time of the same order of
      magnitude of the physiological period required to restore the coronary lesion
      (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit
      the in-stent-restenosis pathology. (c) 2015 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 104B: 1013-1022, 2016.

PMID- 25997170
TI  - Resting electroencephalographic correlates of the clinical response to repetitive
      transcranial magnetic stimulation: A preliminary comparison between unipolar and
      bipolar depression.
AB  - BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BP) are two
      different types of mood disorders, sometimes difficult to distinguish from their
      depressive symptoms, and for which repetitive transcranial magnetic stimulation
      (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been proposed to treat
      refractory patients. Here we studied whether the electroencephalogram (EEG) at
      rest could be used to predict the therapeutic response to left DLPFC 10 Hz rTMS,
      and to which extent BP and MDD patients show similar correlation between the
      clinical response and the cortical networks at rest. METHODS: Eight MDD (6
      females) and 10 BP patients (6 females) were included. The rTMS therapy consisted
      of 10 to 20 neuronavigated sessions, with 2000 pulses continuously applied at
      120% motor threshold for each session. RTMS sessions at the beginning, middle and
      end of the therapy were performed while recording EEG signals. EEG spectral power
      was partitioned using the common physiological frequency bands and was
      statistically analysed at the scalp level and after cortical source
      reconstruction. RESULTS: We found significantly higher power in theta and beta
      bands in BP patients than in MDD patients, mainly localised in the prefrontal
      cortex. In addition, responders showed higher power in delta and theta bands in
      parietal regions and weaker frontal alpha power, when compared to non-responders.
      DISCUSSION: These preliminary findings on a small cohort suggest that pre
      treatment EEG oscillatory patterns may have some predictive value regarding rTMS
      therapy, both for MDD and BP disorders.

PMID- 25997171
TI  - Non-linear processing of a linear speech stream: The influence of morphological
      structure on the recognition of spoken Arabic words.
AB  - Although the significance of morphological structure is established in visual
      word processing, its role in auditory processing remains unclear. Using
      magnetoencephalography we probe the significance of the root morpheme for spoken
      Arabic words with two experimental manipulations. First we compare a model of
      auditory processing that calculates probable lexical outcomes based on whole-word
      competitors, versus a model that only considers the root as relevant to lexical
      identification. Second, we assess violations to the root-specific Obligatory
      Contour Principle (OCP), which disallows root-initial consonant gemination. Our
      results show root prediction to significantly correlate with neural activity in
      superior temporal regions, independent of predictions based on whole-word
      competitors. Furthermore, words that violated the OCP constraint were
      significantly easier to dismiss as valid words than probability-matched
      counterparts. The findings suggest that lexical auditory processing is dependent
      upon morphological structure, and that the root forms a principal unit through
      which spoken words are recognised. 

PMID- 25997164
TI  - A multilaboratory comparison of calibration accuracy and the performance of
      external references in analytical ultracentrifugation.
AB  - Analytical ultracentrifugation (AUC) is a first principles based method to
      determine absolute sedimentation coefficients and buoyant molar masses of
      macromolecules and their complexes, reporting on their size and shape in free
      solution. The purpose of this multi-laboratory study was to establish the
      precision and accuracy of basic data dimensions in AUC and validate previously
      proposed calibration techniques. Three kits of AUC cell assemblies containing
      radial and temperature calibration tools and a bovine serum albumin (BSA)
      reference sample were shared among 67 laboratories, generating 129 comprehensive
      data sets. These allowed for an assessment of many parameters of instrument
      performance, including accuracy of the reported scan time after the start of
      centrifugation, the accuracy of the temperature calibration, and the accuracy of
      the radial magnification. The range of sedimentation coefficients obtained for
      BSA monomer in different instruments and using different optical systems was from
      3.655 S to 4.949 S, with a mean and standard deviation of (4.304 +/- 0.188) S
      (4.4%). After the combined application of correction factors derived from the
      external calibration references for elapsed time, scan velocity, temperature, and
      radial magnification, the range of s-values was reduced 7-fold with a mean of
      4.325 S and a 6-fold reduced standard deviation of +/- 0.030 S (0.7%). In
      addition, the large data set provided an opportunity to determine the instrument
      to-instrument variation of the absolute radial positions reported in the scan
      files, the precision of photometric or refractometric signal magnitudes, and the
      precision of the calculated apparent molar mass of BSA monomer and the fraction
      of BSA dimers. These results highlight the necessity and effectiveness of
      independent calibration of basic AUC data dimensions for reliable quantitative
      studies. 

PMID- 25997173
TI  - Soil heavy metal pollution and risk assessment in Shenyang industrial district,
      Northeast China.
AB  - To investigate the soil heavy metal pollution characteristics and ecological risk
      factors, 42 samples and six typical soil profiles were collected from the
      Shenyang industrial district in northeast China and were analyzed for contents of
      titanium (Ti), copper (Cu), lead (Pb), zinc (Zn), cobalt (Co), nickel (Ni),
      chromium (Cr) and arsenic (As). Through statistical analysis, it was found that
      the mean concentrations were higher than their background values (Ti =
      4.77>3.8g/kg, Cu = 33.75>22.6 mg/kg, Pb = 45.95>26 mg/kg, Zn = 81.54>74.2 mg/kg,
      Co = 12.91>12.7 mg/kg, Ni = 32.26>26.9 mg/kg, Cr = 83.36>61 mg/kg and As =
      13.69>11.2 mg/kg) but did not exceed their corresponding pollution limits for the
      Chinese Environmental Quality Standard for Soils (State Environmental Protection
      Administration of China, 1995). There were contamination hotspots that may be
      caused by human activities such as smelting plants and sewage irrigation. The
      Enrichment Factor and Ecological Risk Index were used to identify the
      anthropogenic contamination and ecological risks of heavy metals. Soil in the
      study area could be considered lightly or partially polluted by heavy metals.
      According to clustering analysis, distinct groups of heavy metals were
      discriminated between natural or anthropogenic sources. 

PMID- 25997172
TI  - Differences in early speech patterns between Parkinson variant of multiple system
      atrophy and Parkinson's disease.
AB  - In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech
      impairment and their distinguishing features from Parkinson's disease (PD)
      require further exploration. Here, we compared speech data among patients with
      early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and
      perceptual analyses. Variables were analyzed for men and women in view of gender
      specific features of speech. Acoustic analysis revealed that male patients with
      MSA-P exhibited more profound speech abnormalities than those with PD, regarding
      increased voice pitch, prolonged pause time, and reduced speech rate. This might
      be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal
      structures related to speech production. Although several perceptual measures
      were mildly impaired in MSA-P and PD patients, none of these parameters showed a
      significant difference between patient groups. Detailed speech analysis using
      acoustic measures may help distinguish between MSA-P and PD early in the disease
      process. 

PMID- 25997174
TI  - A LC-MS method to quantify tenofovir urinary concentrations in treated patients.
AB  - Tenofovir disoproxil fumarate is a prodrug of tenofovir used in the treatment of
      HIV and HBV infections: it is the most used antiretroviral worldwide. Tenofovir
      is nucleotidic HIV reverse trascriptase inhibitor that showed excellent long-term
      efficacy and tolerability. However renal and bone complications (proximal
      tubulopathy, hypophosphatemia, decreased bone mineral density, and reduced
      creatinine clearance) limit its use. Tenofovir renal toxicity has been suggested
      as the consequence of drug entrapment in proximal tubular cells: measuring
      tenofovir urinary concentrations may be a proxy of this event and it may be used
      as predictor of tenofovir side effects. No method is currently available for
      quantifying tenofovir in this matrix: then, the aim of this work was to validate
      a new LC-MS method for the quantification of urinary tenofovir. Chromatographic
      separation was achieved with a gradient (acetonitrile and water with formic acid
      0.05%) on an Atlantis 5 MUm T3, 4.6 mm * 150 mm, reversed phase analytical
      column. Detection of tenofovir and internal standard was achieved by electrospray
      ionization mass spectrometry in the positive ion mode. Calibration ranged from
      391 to 100,000 ng/mL. The limit of quantification was 391 ng/mL and the limit of
      detection was 195 ng/mL. Mean recovery of tenofovir and internal standard were
      consistent and stable, while matrix effect resulted low and stable. The method
      was tested on 35 urine samples from HIV-positive patients treated with tenofovir
      based HAARTs and did not show any significant interference with antiretrovirals
      or other concomitantly administered drugs. All the observed concentrations in
      real samples fitted the calibration range, confirming the capability of this
      method for the use in clinical routine. Whether confirmed in ad hoc studies this
      method may be used for quantifying tenofovir urinary concentrations and help
      managing HIV-positive patients treated with tenofovir.

PMID- 25997175
TI  - Venous Nicking Without Arteriovenous Contact: The Role of the Arteriolar
      Microenvironment in Arteriovenous Nickings.
AB  - IMPORTANCE: Arteriovenous nickings (AVNs) in the retina are the cause of retinal
      vein occlusions and are also surrogates of cerebrovascular aging. The prevalent
      mechanistic model of AVNs stating that arteries crush veins remains somewhat
      unchallenged despite the lack of evidence other than fundus photographs. Here, we
      observed that venous nicking may be observed in the absence of physical contact
      with an arteriole. OBSERVATIONS: This observational study, conducted from January
      2013 to September 2014, included 7 patients showing remodeling of a venous
      segment close to a retinal arteriole without arteriovenous overlap were imaged by
      adaptive optics imaging. Affected venous segments showed a variable association
      of nicking, narrowing, deviation, and opacification. Venous segments were
      deviated toward the arterioles in 6 of the 7 cases. The degree of venous
      narrowing ranged from 40% to 77%, while at these sites, the width of the
      intervascular space ranged from 16 um to 42 um. Similar features were identified
      in typical AVNs. CONCLUSIONS AND RELEVANCE: Arteriovenous nickings do not
      necessarily involve an arteriovenous compression. Instead, the topology of venous
      changes suggests a retractile process originating in the intervascular space.
      These findings have important implications for the understanding of retinal vein
      occlusions and of cerebrovascular aging.

PMID- 25997176
TI  - Effect of In doping on the properties and antibacterial activity of ZnO films
      prepared by spray pyrolysis.
AB  - Pure and In-doped ZnO thin films were deposited onto glass substrates by spray
      pyrolysis technique. XRD results showed that all films were polycrystalline in
      nature with the wurzite structure. A change in preferential orientation from
      (002) to (101) plane was observed with increase in content of Indium. A reduce in
      crystallite size was observed with increase of In content. The small sized grains
      with the porous nature of the film was observed from SEM analysis. AFM study
      depicted polycrystalline nature and uniformly distributed grains with small pores
      in the doped film. A decrease in band gap was noticed with increase in In
      content. The absence of green emission in PL spectra indicated the decreased
      oxygen defects. The decrease in the resistivity with increase of Hall mobility
      was noted for the doped film. A better antibacterial activity was observed
      against Staphylococcus aureus by doped ZnO thin film. 

PMID- 25997177
TI  - Experimental and theoretical studies of (FT-IR, FT-Raman, UV-Visible and DFT) 4
      (6-methoxynaphthalen-2-yl) butan-2-one.
AB  - In this work, the vibrational spectral analysis was carried out by using FT-Raman
      and FT-IR spectroscopy in the range 4000-50 cm(-1) and 4000-450 cm(-1)
      respectively for 4-(6-methoxynaphthalen-2-yl) butan-2-one (abbreviated as 4MNBO)
      molecule. Theoretical calculations were performed by density functional theory
      (DFT/B3LYP) method using 6-311G(d,p) and 6-311++G(d,p) basis sets. The difference
      between the observed and calculated wavenumber value of most of the fundamentals
      were very small. The complete vibrational assignments of wavenumbers were made on
      the basis of potential energy distribution (PED). The UV-Vis spectrum was
      recorded in the methanol solution. The energy, wavelength and oscillator's
      strength were calculated by Time Dependent Density Functional Theory (TD-DFT) and
      matched to the experimental findings. The intramolecular contacts have been
      interpreted using natural bond orbital (NBO) and natural localized molecular
      orbital (NLMO) analysis. Thermodynamic properties of 4MNBO at different
      temperature have been calculated. The molecular electrostatic potential surface
      (MESP) and Frontier molecular orbital's (FMO's) analysis were investigated using
      theoretical calculations.

PMID- 25997178
TI  - A vibrational spectroscopy study on anserine and its aqueous solutions.
AB  - In this study based on vibrational spectroscopic measurements and Density
      Functional Theory (DFT), we aimed for a reliable interpretation of the IR and
      Raman spectra recorded for anserine in the solid phase and water (H2O) and heavy
      water (D2O) solutions. Initial DFT calculations at the B3LYP/6-31G(d) searched
      possible conformers of the anserine zwitterion using a systematic conformational
      search. The corresponding equilibrium geometrical parameters and vibrational
      spectral data were determined for each of the stable conformers (in water) by the
      geometry optimization and hessian calculations performed at the same level of
      theory using the polarized continuum model (PCM). The same calculations were
      repeated to determine the most energetically preferred dimer structure for the
      molecule and the associated geometry, force field and vibrational spectral data.
      The harmonic force constants obtained from these calculations were scaled by the
      Scaled Quantum Mechanical Force Field (SQM) method and then used in the
      calculation of the refined wavenumbers, potential energy distributions, IR and
      Raman intensities. These refined theoretical data, which confirm the zwitterion
      structure for anserine in the solid phase or aqueous solvents, revealed the
      remarkable effects of intermolecular hydrogen bonding on the structural
      properties and observed IR and Raman spectra of this molecule. 

PMID- 25997180
TI  - Erratum.

PMID- 25997179
TI  - Development of Cobalt Hydroxide as a Bifunctional Catalyst for Oxygen
      Electrocatalysis in Alkaline Solution.
AB  - Co(OH)2 in the form of hexagonal nanoplates synthesized by a simple hydrothermal
      reaction has shown even greater activity than cobalt oxides (CoO and Co3O4) in
      oxygen reduction and oxygen evolution reactions (ORR and OER) under alkaline
      conditions. The bifunctionality for oxygen electrocatalysis as shown by the OER
      ORR potential difference (DeltaE) could be reduced to as low as 0.87 V,
      comparable to the state-of-the-art non-noble bifunctional catalysts, when the
      Co(OH)2 nanoplates were compounded with nitrogen-doped reduced graphene oxide (N
      rGO). The good performance was attributed to the nanosizing of Co(OH)2 and the
      synergistic interaction between Co(OH)2 and N-rGO. A zinc-air cell assembled with
      a Co(OH)2-air electrode also showed a performance comparable to that of the state
      of-the-art zinc-air cells. The combination of bifunctional activity and
      operational stability establishes Co(OH)2 as an effective low-cost alternative to
      the platinum group metal catalysts. 

PMID- 25997181
TI  - Extreme Variation of Nutritional Composition and Osmolality of Commercially
      Available Carbohydrate Energy Gels.
AB  - The provision of exogenous carbohydrate (CHO) in the form of energy gels is
      regularly practiced among endurance and team sport athletes. However, in those
      instances where athletes ingest suboptimal fluid intake, consuming gels during
      exercise may lead to gastrointestinal (GI) problems when the nutritional
      composition of the gel is not aligned with promoting gastric emptying.
      Accordingly, the aim of the current study was to quantify the degree of diversity
      in nutritional composition of commercially available CHO gels intended for use in
      the global sports nutrition market. We surveyed 31 product ranges (incorporating
      51 flavor variants) from 23 brands (Accelerade, CNP, High5, GU, Hammer, Maxim,
      Clif, USN, Mule, Multipower, Nectar, Carb- Boom, Power Bar, Lucozade, Shotz,
      TORQ, Dextro, Kinetica, SiS, Zipvit, Maxifuel, Gatorade and Squeezy). Gels
      differed markedly in serving size (50 +/- 22 g: 29-120), energy density (2.34 +/-
      0.7 kcal/g: 0.83-3.40), energy content (105 +/- 24 kcal: 78-204), CHO content (26
      +/- 6 g: 18-51) and free sugar content (9.3 +/- 7.0 g: 0.6-26.8). Most notably,
      gels displayed extreme variation in osmolality (4424 +/- 2883 mmol/kg: 303
      10,135) thereby having obvious implications for both GI discomfort and the total
      fluid intake likely required to optimize CHO delivery and oxidation. The large
      diversity of nutritional composition of commercially available CHO gels
      illustrate that not all gels should be considered the same. Sports nutrition
      practitioners should therefore consider the aforementioned variables to make
      better-informed decisions regarding which gel product best suits the athlete's
      specific fueling and hydration requirements. 

PMID- 25997182
TI  - [Effects of ozone stress on photosynthesis and dry matter production of rice II 
      you 084 under different Planting densities].
AB  - In order to investigate the effects of ozone stress on photosynthesis, dry matter
      production, non-structural carbohydrate and yield formation of rice, a free air
      ozone concentration enrichment (FACE) experiment was conducted. A super hybrid
      rice cultivar II-you 084 with 3 spacing levels, low plant density (LD, 16 hills
      per m2), medium (MD, 24 hills per m2) and high plant density (HD, 32 hills per
      m2), was grown in the field at current and elevated ozone concentrations (current
      * 1.5). The results were as follows: Elevated ozone significantly reduced leaf
      SPAD value of UI-you 084 by 6%, 11% and 13%, at 63, 77, and 86 days after
      transplanting, respectively. The declines in leaf net photosynthetic rate,
      stomatal conductance and transpiration rate at filling stage increased
      significantly on ozone stress over time. Ozone stress decreased dry matter
      production of rice by 46% from heading stage to plant maturity, thus reduced
      biomass yield by 25%. Elevated ozone decreased the concentration and accumulation
      of soluble carbohydrate and starch in stem of II-you 084 at jointing, heading and
      plant maturity, but significantly increased the dry matter transportation rate.
      No significant interaction was observed between ozone and planting density for
      photosynthesis, dry matter production and non-structural carbohydrate of rice.
      The above results indicated that elevated ozone reduced photosynthesis and growth
      of rice II-you 084 at late growth stage, which had no relationship with planting
      density.

PMID- 25997183
TI  - Author's reply.

PMID- 25997184
TI  - Experts in mouth improvement.

PMID- 25997185
TI  - Patients' best interests at the heart of conservative esthetic dentistry.

PMID- 25997186
TI  - BIOLASE: providing clinicians a solutions-based approach to dental lasers.

PMID- 25997188
TI  - LightWalker(r) dual-wavelength laser from Fotona handles soft and hard tissue
      with care.

PMID- 25997187
TI  - Convergent dental's SoleaTM CO2 laser effective for both hard- and soft-tissue
      ablation.

PMID- 25997189
TI  - Millennium dental's minimally invasive PerioLase(r) MVP-7TM laser: not just for
      periodontitis.

PMID- 25997190
TI  - Oral health managers.

PMID- 25997191
TI  - Improving case acceptance rates: 6 steps for success.

PMID- 25997192
TI  - Unique system ideal for timely, precise scannable impressions.

PMID- 25997193
TI  - Take 1(r) AdvancedTM final impression material: precise delivery, better control.

PMID- 25997194
TI  - Planmeca PlanScanTM makes digital impressioning quick, easy and efficient.

PMID- 25997195
TI  - Never stop learning.

PMID- 25997196
TI  - Smart practice management: 7 keys to retiring early.

PMID- 25997197
TI  - PlanScanTM CAD/CAM solution: producing crowns chairside "easier, better".

PMID- 25997198
TI  - CEREC(r) celebrates 30 years of advances to improve the patient experience.

PMID- 25997199
TI  - Clinical options.

PMID- 25997200
TI  - The "inevitability" of digital radiography in dentistry.

PMID- 25997201
TI  - Paradigm shift: digital processing altering denture fabrication.

PMID- 25997202
TI  - Streamlined Ti-Max Z95L electric handpiece doesn't sacrifice torque and power.

PMID- 25997203
TI  - Zest Anchors' CHAIRSIDETM Denture Prep & Polish Kit Smoothes overdenture
      preparation.

PMID- 25997204
TI  - Academician Vasile Anestiadi (1928-2014).

PMID- 25997205
TI  - Prognostic value of initial elevation in cardiac troponin I level in critically
      ill patients without acute coronary syndrome.
AB  - BACKGROUND: Cardiac troponin I levels are often obtained to help rule out acute
      coronary syndrome. OBJECTIVE: To determine if elevation of troponin level within
      24 hours for patients without acute coronary syndrome admitted to the intensive
      care unit provides important prognostic information. METHODS: Patients without
      acute coronary syndrome admitted to the intensive care unit were prospectively
      divided into 2 groups according to highest serum level of cardiac troponin I
      within 24 hours of admission (elevated > 0.049 ng/mL; control <= 0.049 ng/mL).
      Hospital mortality, incidence of intubation, and other parameters were compared
      between the 2 groups. RESULTS: Patients with elevated troponin level (n = 40) had
      higher mortality than did control patients (n = 50) (35% vs 12%; P= .01).
      Compared with control patients, patients with elevated levels were more likely to
      be intubated (41% vs 17%; P= .02). CONCLUSION: Critically ill patients without
      acute coronary syndrome with elevated levels of cardiac troponin I at admission
      had higher mortality and more intubations than did control patients.

PMID- 25997206
TI  - Introduction.

PMID- 25997207
TI  - [Potential clinical benefit of therapeutic drug monitoring of imatinib in
      oncology].

PMID- 25997209
TI  - [Advances in clinical research on non-infectious liver diseases in 2014].

PMID- 25997208
TI  - [What's new in 2014 for treatment of hepatitis C].

PMID- 25997210
TI  - [Advances in research on hepatocellular carcinoma in 2014].

PMID- 25997211
TI  - Establishing controls to ensure accurate charge capture.

PMID- 25997212
TI  - Loan program makes care more affordable.

PMID- 25997213
TI  - Staying one step ahead of claim rejections.

PMID- 25997214
TI  - [Determination of the glycemic index of the wild rice and the effects of wild
      rice on insulin resistance in rats].
AB  - OBJECTIVE: To investigate the glycemic index ( GI) of wild rice, and observe the
      effects of wild rice on the insulin resistance ( IR) rats induced by high fat
      diet. METHODS: With 50g glucose as control, measured healthy adults ( n = 8 )
      blood glucose levels after eating 67 g wild rice within 2 h, and using Jenkins
      and Wolever formula to calculate the GI. 50 male SD rats were randomly divided
      into negative control group, IR model group, high-dose of wild rice group, low
      dose of wild rice group and white rice-flour group, continuous feeding eight
      weeks. Fasting blood glucose (FPG), fasting insulin (INS), glycosylated
      hemoglobin (HbAlc) and glucagon (GC) were measured, and insulin resistance index
      (HOMA-IR) was calculated. RESULTS: The GI of wild rice was 53. 72 . Compared.
      with the negative control group, the rats of IR model group and white rice-flour
      group had higher body weight, FPG, INS, GC levels and HOMA-IR (P <0. 05).
      Compared with the white rice-flour and IR model group , FPG, INS, GC levels and
      HOMA-IR in rats fed high-dose of wild rice and low-dose of wild rice diet were
      significantly decreased (P <0. 05). The rats fed with low-dose of wild rice diet
      had slightly increased FPG, INS, GC levels and HOMA-IR, but the difference was
      not statistically significant. CONCLUSION: Wild rice is a low glycemic index
      food, while wild rice can improve the resistance in rats induced by high fat
      diet, and replace 50% of the refined rice and flour with wild rice can improve
      insulin resistance in rats.

PMID- 25997215
TI  - [Effects of exercise and conjugated linoleic acid on PPARgamma in adolescent
      obese rats].
AB  - OBJECTIVE: To explore effects of exercise and conjugated linoleic acid (CLA) on
      PPARy in adolescent obese male SD rats. METHODS: obese rats were modeled with
      high fat feeding, 32 obese rats were selected and randomly divided into control
      group, static + CLA group, exercise-treated group, exercise + CLA treated group.
      Blood and adipose tissue. were collected after 8 weeks, and blood lipid was
      measured. PPARgamma mRNA gene expression in adipose tissue was tested using qRT
      PCR, PPARgamma protein expression in adipose tissue by immunohistochemistry,
      concentration of PPARgamma in plasma by ELISA. RESULTS: (1) TC level of static +
      CLA group and exercise group were lower than the control group (P <0. 05). TG
      level of the exercise group and exercise group + CLA were lower than the control
      group, static + CLA group (P <0. 01). LDL-c level of exercise group and exercise
      + CLA group was higher than the control group (P <0. 05), HDL-c level have no
      difference in groups. (2) PPAR-gamma concentration in plasma in exercise group,
      exercise + CLA group was higher than the control group and static + CLA group (P
      <0. 01). Expression of PPARy mRNA in adipose tissue in exercise group, exercise +
      CLA group was higher than the control group and static + CLA group (P <0. 01).
      PPARgamma concentration in plasma and expression of PPARy mRNA in adipose tissue
      in static + CLA group were higher than control group but with no statistical
      significance. (3) The situation of PPARgamma protein expression was the same with
      the expression of PPARgamma mRNA. CONCLUSION: 8 weeks of different intervention
      methods can reduce the concentration of TG and TC in blood lipid index in
      adolescent obese rats, TG of exercise and exercise + CLA is better decreasing
      than simply add CLA. Exercise and exercise + CLA can improve the expression of
      PPARy mRNA and protein in adipose tissue and plasma PPARgamma concentration in
      rats.

PMID- 25997216
TI  - [Effects of biotin on blood glucose regulation in type 2 diabetes rat model].
AB  - OBJECTIVE: To explore the effect of biotin on blood glucose regulation in rats
      and its possible mechanism. METHODS: According to initial body weight and blood
      glucose, we randomly divided the 90 Wistar rats into 5 groups: the normal control
      group, model group, biotin low-dose group (0. 6mg/kg BW), biotin medium-dose
      group (3. 0 mg/kg BW) and biotin high-dose group (6. 0 mg/kg BW). After 2 months,
      the rats with HFS feed were injected with STZ (25 mg/kg BW) to manufacture
      diabetic rat model. After the OGTT experiment at 10th week, the blood glucose,
      insulin, liver/muscle glycogen and other biochemical indexes were detected. The
      GCK, PCK1 mRNA expression were measured with RT-PCR method. RESULTS: Biotin has a
      certain improvement on postprandial glucose in diabetic rats. Compared with the
      model group, the AUC and the 30min postprandial blood glucose of biotin high-dose
      group were significantly decreased (P <0. 05). Biotin can affect some key enzyme
      gene in glucose metabolism, such as GCK, PCK1. CONCLUSION: The possible mechanism
      of the decreasing biotin blood sugar in diabetic rats may by promoting the
      synthesis of glycogenand reducing gluconeogenesis.

PMID- 25997217
TI  - [Association between CCND1 polymorphisms and chromosomal damage among workers
      exposed to 1,3-butadiene].
AB  - OBJECTIVE: To investigate the association between CCND1 polymorphisms and the DNA
      and chromosome damage in peripheral blood lymphocytes among workers exposed to
      1,3-butadiene(BD). METHODS: 171 workers exposed to 1,3-butadiene and 55 controls
      without occupational BD exposure were investigated. Cytokinesis-block
      micronucleus(CBMN) detection and comet assay were used to evaluate the
      chromosomal and DNA damage levels in peripheral blood lymphocyte. And the
      genotypes of CCND1 were detected by PCR-RFLP. Personal information including
      occupational history, age, sex, smoking and drinking status was collected by the
      questionnaire. RESULTS: The rate of CBMN and OTM of lymphocyte in BD exposed
      workers[(7. 17 +/- 5. 09)% and 4. 65(95% CI 3. 49 - 5. 98), respectively] were
      higher than those in controls[(3. 82 +/- 2. 37)% and 2. 38 (95% CI 0. 82 - 3.
      98), P < 0. 01. Multivariate analysis of covariance revealed that in BD workers.
      The subjects with CCND1 A870G AA allele have significantly higher risk for DNA
      damage than subjects with GG allele (P < 0. 05). CONCLUSION: Under present BD
      exposure levels, both comet assay and cytokinesis-block micronucleus test could
      be sensitive group biomarkers to use to monitor the genotoxicity of BD
      occupational exposure. CCNDI A870G polymorphisms might influence the
      susceptibility of DNA damage in BD exposed workers.

PMID- 25997218
TI  - [Establishment a method for identification of the poly(ADP-ribose) binding
      proteins induced by benzo(a)pyrene].
AB  - OBJECTIVE: To establish a method for identification of the poly(ADP-ribose)
      binding proteins induced by benzo (a) pyrene. METHODS: Poly (ADP-ribose) binding
      protein were screened by immunoprecipitation assay and further separated by high
      performance liquid chromatography (HPLC) and two dimensional electrophoresis,
      then identified by MALDI-TOF-MS/MS. The proteins sequence were identified by two
      methods and compared the common binding motif with literature reports. RESULTS:
      Three poly (ADP-ribose) binding proteins were identified by MALDI-TOF-MS/MS
      combined with immunoprecipitation assay and HPLC, and twelve poly (ADP-ribose)
      binding proteins were identified by MALDI-TOF-MS/MS combined with
      immunoprecipitation assay and two dimensional electrophoresis. Most of them have
      a common binding motif which was consistent with the reported. CONCLUSION:
      Combined the immunoprecipitation assay and two dimensional electrophoresis with
      MALDI-TOF-MS/MS could be used to analyze the poly(ADP-ribose) binding proteins,
      and these proteins have a common conserved binding motif.

PMID- 25997219
TI  - [Identification of hexavalent chromium reducing bacteria Cr4-1 and optimization
      of its reduction conditions].
AB  - OBJECTIVE: To identify the hexavalent chromium reduction Cr4-1, and to study the
      better conditions of the bacterial growth and its Cr(VI) reduction. METHODS: The
      physiological and biochemical methods and 16s rDNA sequencing were used for
      identification of bacteria Cr4-1. The influence of temperature, pH, initial Cr
      (VI) concentration and shaking speed on bacterial growth and Cr (VI) reduction
      were studied. Mass balance analysis was used to analyze the end products of the
      reduction reaction. RESULTS: A Cr(VI) reducing bacteria Cr4-1, screened from
      acclimated activated sludge, was identified as Bacillus cereus. The appropriate
      conditions of bacterial growth was 25  degrees C, pH 7 to 8, shaking speed 150
      r/min, while the suitable conditions for Cr(VI) reduction was 35  degrees C, pH 8
      to 9. When the initial Cr(VI) concentration increased from 20 mg/L to 60 mg/L,
      the reduction rate decreased gradually. Under the suitable reducing conditions,
      when the initial concentration of Cr (VI) was 30 mg/L, the reduction rate could
      up to 100% in 9 h. The end product was soluble trivalent chromium. CONCLUSION:
      Strain Cr4-1 had a good effect on Cr (VI) reduction and the final product was
      soluble trivalent chromium.

PMID- 25997220
TI  - [Research on the smoking status and influence factors among female sex workers
      and general migrant women in Shanghai City].
AB  - OBJECTIVE: To explore the smoking status and related influence factors among
      female sex workers (FSW) and general migrant women (GMW) in Shanghai City, and
      provide references for health intervention. METHODS: A total of 721 FSW and 675
      GMW, recruited by a multiple stage cluster sampling method from Minhang District,
      Shanghai city, were interviewed. Socio-demographic characteristics and the
      smoking status were collected by questionnaire interview, while the quality of
      life (QOL) among participants were evaluated by WHOQOL-BREF. RESULTS: The smoking
      rate within FSW (39. 1%) was significantly higher than GMW (2.7%). When compared
      with GMW, QOL scores among FSW were signifiantly lower in four domains ( physio
      domain F = 55. 50, P <0. 001, psychi-domain F =59. 07, P <0. 001, social
      relationship domain F = 157. 46, P < 0. 001 and environmental domain F = 65. 08,
      P < 0. 001). The multivariate analysis showed that higher score of psychi-domain
      (OR = 0. 893, 95% CI 0. 839 - 0. 950), married (OR =0. 590, 95% CI 0. 395 - 0.
      880), older age group (OR =0. 590, 95% CI 0. 395 - 0. 880) and GMW (OR = 0. 077,
      95% CI 0. 043 - 0. 141.) were protecting factors for smoking, whereas not having
      a permant partner (OR = 1. 610, 95% CI 1. 114 - 2. 328), staying in Shanghai <= 1
      year (OR = 1. 537, 95% CI 1. 109 - 2. 132) and low income group (OR = 1. 956, 95%
      CI 1. 445 - 2. 650) were risk factors for smoking. CONCLUSION: The rate of
      smoking is significantly higher in FSW, when compared: with GMW. The effective
      preventive strategies which concentrate on the influence factors should be taken
      to reduce smoking in the target population.

PMID- 25997221
TI  - [Effect of the capacity of emotion management on the social anxiety and
      aggressive behavior among 4 -6 grade pupils].
AB  - OBJECTIVE: To explore the effect of emotion management ability on the social
      anxiety and aggressive behavior among 4 - 6 grade pupils. METHODS: The grade
      four, five and six pupils from Bengbu City were investigated using stratified
      cluster random sampling. The questionnaire contents included general condition,
      emotion management ability, aggressive behavior and social anxiety, and the
      relationships of which were analyzed using partial correlation and hierarchical
      regression method. RESULTS: The score of aggressive behavior in boys (72. 74 +/-
      18. 09) was higher than that in girls (66. 31 +/- 17. 53) (P < 0. 01), and the
      aggressive behaviors in grade five students (71. 76 +/- 18. 06) were higher than
      that in grade four (69. 24 +/- 18. 95) and six students (68. 40 +/- 17. 19) (P
      <0. 05). When gender and grade variables, the aggressive behaviors were
      negatively correlated with emotion management ability (r = - 0. 463, P < 0. 01) ,
      and were positively correlated with social anxiety (r = 0. 229, P < 0. 01) , and
      the emotion management ability was negatively correlated with social anxiety ( r
      = - 0. 234, P < 0. 01). Emotion management ability played the mediation and
      regulation roles on the social anxiety and aggressive behavior (P < 0. 01), which
      accounting for 46. 08% and 3. 50% of the total effect, respectively CONCLUSION:
      Emotion management ability can play the partial mediation role on the social
      anxiety and aggressive behavior in 4 - 6 grade pupils. Improving the emotion
      management abilities can reduce their social anxieties and aggressive behaviors.

PMID- 25997222
TI  - [Postpartum weight retention in Beijing, Suzhou and Guangzhou women and its
      associated factors].
AB  - OBJECTIVE: To investigate the prevalence of postpartum weight retention (PPWR) in
      urban Chinese women, and to explore its associated factors. METHODS: Cluster
      sampling methods were used to select a total of 6 hospitals in Beijing, Guangzhou
      and Suzhou. A total of 578 women in the 0 - 1 months, 1 - 2 months, 2 - 4 months
      and 4 - 8 months postpartum participated in this study. Anthropometric indicators
      of height and weight were measured for each participant. Questionnaire was used
      to obtain the sociodemographic characteristics. Maternal information of pre
      pregnancy weight and gestational weight gain were obtained by medical records.
      RESULTS: The pre-pregnancy BMI of participants was (20. 8 +/- 2. 7), while
      postpartum BMI was (23. 4 +/- 3. 2). PPWR decreased over time, however, 53. 4% of
      women had PPWR over 5kg at the 4 - 8 months postpartum. 32. 6% of women were
      overweight or obese at 4 - 8 months postpartum. Women with PPWR >0kg at 4 - 8
      months postpartum had a higher gestational weight gain ((16.5 +/- 5.5) kg)
      compared to those with PPWR<=0 kg ((13.0 +/-4.7) kg). Women with higher education
      experience had a higher proportion of weight retention over 0 kg at 4 - 8 month
      postpartum. CONCLUSION: PPWR is a serious health and nutritional problem in
      Chinese women, where excess in gestational weight gain is associated with PPWR.
      To improve the health and lifestyle of perinatal women, a comprehensive health
      education and health intervention should be explored.

PMID- 25997223
TI  - [Level of different energy metabolism on constitution of women in Xi' an City].
AB  - OBJECTIVE: To analyze the relationship between different level of surplus energy
      and constitution health among middle-aged and elder females. METHODS: Multi-stage
      stratified random sampling method was used and 650 residents aged 40 - 60 years
      in Xi' an City were selected for measurement of body shape, function, blood
      biochemistry and psychology indicators and questionnaire survey of nutritional
      and physical activity status. The subjects were divided into the following four
      groups according to surplus energy (SE) classification by using of quartile
      method, When SE < P25 for the low surplus energy group, P25 <= SE < P50 for the
      moderate surplus energy group, P50 <= SE < P75 for the high surplus energy group,
      P75 < SE for higher surplus energy group. RESULTS: Body mass, waist
      circumference, hip circumference, arm skinfold thickness, abdominal skinfold
      thickness, leg skinfold thickness, body mass index, waist-hip ratio and body fat
      rate among surplus energy groups was statistically significant (P < 0. 05 or P <
      0. 01). Cardiopulmonary function and mental health level of the high energy group
      and the moderate surplus energy group were better than the low surplus energy
      group and higher surplus energy group, it was statistically significant (P <0.
      05), and the level of glucose, TG, TC, LDL declined significantly and the level
      of HDL increased remarkably (P < 0. 05). CONCLUSION: The energy intake of dietary
      and the energy consumption of physical activity are factors influencing the level
      of constitution health.

PMID- 25997224
TI  - [Prevalence of self-reported food allergy and food intolerance and their
      associated factors in 3 - 12 year-old children in 9 areas in China].
AB  - OBJECTIVE: To measure the prevalence and the associated factors of food allergy
      and food intolerance in 3 - 12 year-old children in 9 areas in China. METHOD:
      1792 children selected by multistage cluster sampling method from 7 cities and 2
      rural areas, from November 2011 to April 2012, with a face-to-face survey to
      children and their parents, and the logistic regression was used to analyze the
      associated factors of food allergy and food intolerance of children. RESULTS: The
      prevalence of self-reported food allergy and food intolerance were 8. 4% and 7.
      7%, respectively. The common foods led to food allergy reported by children's
      parents were seafood, fish, egg, fruit and milk. The parental allergy was risk
      factors of food allergy of children (OR = 4. 49 (95% CI 2. 52 - 8. 01), P <0.
      01). The picky eating was risk factor of food intolerance of children(OR = 2.
      40(95% CI 1. 43 - 4. 02), P < 0. 01). And the education of mother was protective
      factor of food intolerance of children (the mother with college degree and above
      relative to with middle school degree and below (OR = 0. 40 (95% CI 0. 20 - 0.
      80), P = 0. 01). CONCLUSION: Children' s food allergy and food intolerance were
      associated with genetic factors and environmental factors included parental
      education and family economic status. Variable foods were necessary for children'
      s growth and development, therefore, it is demanded to conduct intervention
      studies based on the associated factors.

PMID- 25997225
TI  - [Survey on diet and nutrition intake for customers from out-home eating in
      Beijing].
AB  - OBJECTIVE: To assess dietary intake of customers from out-home eating, and
      evaluate their energy and main nutrition closely related with chronic disease
      consumption in one dinner. METHODS: On dinner time (lunch or supper), 2204
      customers randomly selected in six middle-level table-service restaurants in
      Beijing, were investigated their food consumption by single-blind recording their
      ordered dishes weight before and after eating. According to the dish recipes,
      cooking way, and food composition database or measured data, food consumption and
      energy, protein, fat and sodium intake were evaluated. RESULTS: The mean intake
      of foods for a standardized man per dinner included 76 g cereals, 162 g
      vegetables, 11 g fruits, 128g meat, 50g fishery products, 10g eggs, 12 g legumes,
      15 g pure energy food, 28 g oil, 7 g salt, 68. 1 g juice, and 7. 3 g alcohol,
      with 4648 kJ energy, 54. 6 g protein, 62. 3 g fat, 88. 0 g carbohydrate, 10. 7 g
      cholesterol and 2920 mg sodium. The percentage for energy suppliers were
      respectively protein 20. 7%, fat 52. 7%, carbohydrate 29. 4%. Contrast to 4180
      kJ/1000 kcal energy intake, the food density for oil and salt was 2 times, and
      meat 3 times over that suggested by Chinese Dietary Pagoda. CONCLUSION: Out-home
      eating per dinner supplies nearly daily-need fat and sodium, that partially
      contributes to high intake of animal foods.

PMID- 25997226
TI  - [Prevalence of vegetarians and vegetarian's health dietary behavior survey in
      Shanghai].
AB  - OBJECTIVE: To assess the prevalence of vegetarians in the whole Shanghai
      population, and to know the vegetarians' brief and behavior on diet, nutrition
      and health. METHODS: First, a multi-staged, stratified, clustered random sampling
      design was used. A total representative sample of 4 004 Shanghai resident
      subjects were asked if they were vegetarians and what type of vegetarian they
      were by a well-designed questionnaire. Second, from ten vegetarian restaurants
      located in Shanghai. 473 adult vegetarians completed a questionnaire about
      vegetarian status, among whom 274 vegetarians completed a detailed questionnaire
      about their brief and behaviors on diet, nutrition and health status. RESULTS: Of
      4 004 subjects, 0.77% were vegetarians (0.45% were lacto-vegetarians and 0. 12%
      were vegans). The average age was 65. 0 years. 74. 2% of the vegetarians were
      female. Of 473 vegetarians, 70. 2% of the vegetarians had college or higher
      education. Compared to vegans, lacto-ovo-vegetarians were significantly younger
      and had higher educational level. The main reasons for choosing a vegetarian
      lifestyle were religion (49. 3%) and health (31. 3%). Furthermore, more vegan
      tend to be Buddhist. Vegetarians were more concerned about their health (209/274,
      76. 5%) , the consumption of balance diets (183/274, 66. 8%). Comparing with
      lacto-ovo-vegetarians (58. 3%) more vegans (70. 4%) believed in that vegetarian
      diet is a kind of healthy dietary pattern and will not have any nutrients
      deficiency (P = 0. 037). Vegetarians consumed more healthy foods (e. g.,whole
      grains, vegetables, soy products, and nuts) than the general population (P < 0.
      01). Only 5. 8% of the vegetarians took dietary supplements. CONCLUSION: 0. 77%
      of population in Shanghai was vegetarian. The two main reasons for adopting a
      vegetarian lifestyle were religion and health. The vegetarians tend to have more
      nutrition knowledge, better attitude and behavior on health. However, most of the
      vegetarians had not realized the nutrient deficiency risk of vegetarian diets.

PMID- 25997227
TI  - [Nutrition and health survey of children and youth in Lishui District, Nanjing
      City].
AB  - OBJECTIVE: To investigate the health and nutrition status of children in rural
      area of Lishui District, Nanjing City. METHODS: Cluster random sampling and the
      stratified sampling methods were used to recruit participants. Refer to the WHO
      child growth standards, Z score method was used to evaluate physical growth of
      the group. Dietary research was conducted by the food frequency
      questionnaire(FFQ), and referring to the 2002 food composition tables of China to
      evaluate the daily dietary intakes. RESULTS: BAZ scores showed 0 - 17 years old
      children obesity prevalence rate was 9. 0%, overweight was 18. 2%, angular and
      malnutrition were co-existed with the prevalence rates were 9. 1%, 1. 9%
      respectively. The average cooking oil was (27 +/- 7. 3) g, and children daily
      intakes of vitamin A, vitamin B1, vitamin B2, vitamin C and calcium suitable
      rates were less than 50% according to the recommendation of Chinese DRIs.
      CONCLUSION: Rural children suffered from the problems of obesity and emaciated
      dietary structure is irrational and dietary nutrients intakes do not reached the
      demands of Chinese DRIs.

PMID- 25997228
TI  - [Study on sub-health status and the relationship between it and personal life
      habits of grade one students in high school in Nanchang City].
AB  - OBJECTIVE: To investigate the prevalence and its influential factors about
      personal life habits of sub-health of grade one students in high school in
      Nanchang City. METHODS: A self-designed sub-health questionnaire was used to
      measure the sub-health of 653 grade one students in high school in Nanchang
      sampled with stratified randomly cluster sampling. RESULTS: The prevalence of sub
      health among the students was 85. 2% , and the prevalence. of physiological sub
      health, psychological sub-health and social sub-health was 64. 3%, 55. 9% and 74.
      7% respectively. In their personal life habits, the degree of activity,
      vegetables and fruits consumed, staying up late were the main influencing factors
      of sub-health (P < 0. 05). Girls, students in non-key class, cadres students,
      dieting students, those spending less time on physical exercises or eating less
      vegetables and fruits or staying up late more often were reported a higher rate
      of physiological sub-health (P <0. 05). Boarders or students in non-key class had
      a higher rate of psychological sub-health (P < 0. 05). Non-cadres students, those
      having less activity or having more time for entertainment or eating less
      vegetables and fruits had a higher risk of suffering social sub-health (P < 0.
      05). CONCLUSION: The grade one students of high school in Nanchang had a high
      prevalence of sub-health. The prevalence of their sub-health could be effectively
      reduced by changing their bad habits of personal life. More attention should be
      given to girls, boarders, non-cadres students and students in non-key class.

PMID- 25997229
TI  - [Relationship among resilience, coping style and mental health of newly recruited
      workers born after 1990 in manufacturing industry of Shenzhen City].
AB  - OBJECTIVE: To explore the relationship among psychological resilience, coping
      styles and mental health of newly recruited production line workers who were horn
      after 1990 in three manufacturing factories in Shenzhen. METHODS: Production line
      workers who were born after 1990 and started working one week ago were selected
      from three manufacturing factories in Shenzhen. The Chinese Connor-Davidson
      Resilience Scale, Simplified Coping Stlye Questionnaire and General Health
      Questionnaire were used to assess their psychological resilience, psychological
      pressure, and mental health. A path analysis was carried out by Amos version 17.
      0. RESULTS: Significantly positive correlation between the resilience and mental
      health (P < 0. 01), mental health and psychological resilience were positively
      related to active coping style (P < 0. 01), mental health and resilience were
      nagatively related to passive coping style (P < 0. 01). The structural equation
      model showed that the psychological resilience had both direct and indirect
      effect on mental health with the mediation effect of active coping styles and
      passive coping style. CONCLUSION: There are linear relationships between
      psychological resilience, coping styling and mental healthof the new recruits in
      Shenzhen manufacturing industry, and the partial indirectly of psychological
      resilience on mental health is potential realized through active coping styles
      and passive coping styles.

PMID- 25997230
TI  - [Analysis on influence factors of health risk behaviors of Tujia and Miao
      adolescents in Xiangxi Area].
AB  - OBJECTIVE: To understand the health risk behaviors status and influence factors
      of Tujia and Miao adolescents in Xiangxi Area. METHODS: By the method of layered,
      random and total sampling, questionnaire survey about dietary bias, current
      smoking, current drinking, suicidal ideation, internet addiction and lack of
      physical exercise was taken to 2094 Tujia and Miao adolescents. Logistic
      regression analysis was used to analyze the risk factors of health risk
      behaviors. Results The report rates of dietary bias, current smoking, current
      drinking, suicidal ideation, internet addiction and lack of physical exercise
      were 27. 84%, 18. 29%, 28. 03%, 21. 68%, 5. 25% and 52. 82%, respectively.
      Logistic regression analysis result showed that the risk factor of dietary bias
      was depression(OR = 1. 352, P =0. 026), the protective factor were schoolboy (OR
      =0.765, P=0.008) and in residence(OR =0.743, P =0.004). The risk factor of
      current smoking were schoolboy (OR =6. 782, P =0. 000), insomnia(seldom or
      sometimes OR = 1. 516, P = 0. 013, often or always OR = 2. 738, P = 0. 000),
      internet addiction (OR =2.389, P =0. 000), fight(OR = 2. 481, P = 0. 000) and
      current drinking(OR = 4. 060, P = 0. 000), the protective factor was school
      record (average OR = 0. 699, P = 0. 026, above average or good OR = 0. 437, P =
      0. 000). The risk factor of current drinking were schoolboy (OR = 1. 829, P = 0.
      000), insomnia (seldom or sometimes OR = 1. 550, P = 0. 002, often or always OR =
      1. 754, P = 0. 004), internet addiction (OR = 1. 901, P =0. 004), fight (OR =
      l.785, P = 0. 000)and current smoking (OR = 4. 016, P = 0. 000). The risk factor
      of suicidal ideation were lonely(seldom or sometimes OR = 1. 823, P =0. 010,
      often or always OR = 4. 445, P =0. 000), depression (OR = 3. 226, P = 0. 000) and
      only child (OR = 1. 612, P = 0. 003), the protective factor was schoolboy (OR =0.
      648, P = 0. 000). The risk factor of internet addiction were schoolboy (OR = 2.
      480, P = 0. 000) depression (OR = 2. 650, P = 0. 000) and mainly to play games(OR
      = 4. 631, P = 0. 000). The risk factor of lack of physical exercise were high
      school student (OR = 1. 536, P =0. 000) and depression(OR = 1. 410, P = 0. 003),
      the protective factor were schoolboy (OR ='0. 581, P = 0. 000) and school record
      (average OR = 0. 798, P = 0. 036, above average or good OR = 0. 609, P = 0. 000.
      CONCLUSION: Tujia and Miao boys were more prone to smoking and drinking behavior,
      while girls were likely to happen dietary bias, suicidal ideation and lack of
      physical exercise behavior. Miao students were high-risk population of smoking
      and drinking behavior. Insomnia and depression became risk factors of multiple
      health risk behaviors.

PMID- 25997231
TI  - [Health risk assessment on pesticide residues in drinking water in Shenzhen].
AB  - OBJECTIVE: To conduct a health risk assessment of pesticide residues and its
      annual trend analysis in drinking water in Shenzhen City. METHODS: The water
      quality monitoring data of product water, pipe water and secondary supply water
      during from 2011 to 2013 were collected and analyzed. The risk evaluation models
      recommended by the U. S. Environmental Protection Agency (USEPA) were employed to
      perform health risk assessments for children and adults on the 12 non
      carcinogenic materials (namely, heptachlor, pentachlorophenol,
      hexachlorocyclohexane, hexachlorobenzene, DDT, malathion, glyphosate, dimethoate,
      bentazone, atrazine, chlorothalonil, furadan). Results The results of the
      analysis for water quality from 84 factory samples, 11 peripheral samples and one
      secondary supply water sample showed that all of the measured indicators in the
      above mentioned water samples met the National Health Standards (GB 5749-2006)
      published by Ministry of Health of the People's Republic of China. The adults and
      children' s health indices (HIs) of the 12 non-carcinogenic materials were
      greater than 1 (2. 323 - 6. 312). Dimethoate in factory and peripheral water
      samples posed the largest risks of harm among the non-carcinogenic pollutants
      measured. And its HIi were also greater than 1 (1. 995 - 5. 094) and followed by
      hexachlorobenzene and heptachlor. Annual rising trend on health risk of the 12
      pesticide residues indicated that their HIT on adults was 2323. 18 x 10(-3) in
      2011, 2340. 18 x 10(-3) in 2012 and 2431. 97 x 10(-3) in 2013, and on children
      2965. 07 x 10 (-3) in 2011, 2986. 77 x 10(-3) in 2012 and 3103. 93 x 10(-3) in
      2013, respectively. This study also suggested that the average risk of peripheral
      water samples (HIT was equal to 2619. 64 x 10(-3) was greater than that of
      factory samples (HIT was same as 2366. 92 x 10(-3), and more children' s health
      risk than adults' risk. CONCLUSION: Health risks of pesticide residues in
      drinking water in Shenzhen have exceeded the threshold value and dimethoate was
      the main hazard and more children's health risk than adults' risk. Furthermore,
      there was an annual rising slowly trend on health risks of pesticide residues in
      drinking water.

PMID- 25997233
TI  - [Effects of selenium compounds on proliferation, migration and adhesion of HeLa
      cells].
AB  - OBJECTIVE: To explore the effects of methylseleninic acid (MeSeA),
      selenomethionine (SeMet) and methylselenocysteine (MeSeCys) on proliferation,
      migration and adhesion of HeLa cells. METHODS: HeLa cells were cultured and
      treated with MeSeA, SeMet and MeSeCys for 12 - 72 h respectively. MTT assay,
      healing assay and in vitro cell Matrigel adhesion assay were used to detect the
      proliferation, migration and adhesion of HeLa cells. RESULTS: Compared to the
      control group, the proliferation of HeLa cells was remarkably inhibited by MeSeA
      (P <0. 01). The migration of HeLa cells in MeSeA group was inhibited by 34% (P <
      0. 05) and 26% (P < 0. 05) in 4 h and 8 h, respectively. However, the migration
      of HeLa cells with inhibitions of 18% and 13% was in SeMet group in 4 h and 8 h.
      The inhibitions of HeLa cell migration in MeSeCys group was 28% (P < 0.05) and 5%
      in 4 h and 8 h, respectively. In addition, the adhesive function of HeLa cells in
      the MeSeA group, the SeMet group as well as the MeSeCys group were inhibited by
      36% (P < 0. 01), 25% and 49% (P < 0. 01). CONCLUSION: The proliferation and
      migration of HeLa cell were effectively inhibited by MeSeA, while the adhesive
      function of HeLa cell was remarkably inhibited by MeSeCys.

PMID- 25997232
TI  - [Effects of octreotide on liver gluconeogenesis in obesity rats fed a high fat
      diet].
AB  - OBJECTIVE: To verify the effects of octreotide on liver gluconeogenesis in high
      fat diet-induced obesity rat. METHODS: Male SD rats were randomly assigned to
      control (n = 16) and high-fat diet group (n = 40). After 24 weeks, obese rats
      selected from high-fat diet group were placed into obese group (n = 16) and
      octretide-treated group (n = 16). Rats in the octreotide-treated group were
      subcutaneously injected with octreotide per 12 h (40 mg/kg body weight) for 8
      days. Body lengths, body weight, fasting plasma glucose (FPG), triglyceride (TG),
      total cholesterol (TC), fasting serum insulin and plasma somatostatin (SST)
      levels were measured. The Lee' s index and HOMA index were calculated. Expression
      of glucose-6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (Pepck) and
      forkhead box-containing protein 0 subfamily-1 (Foxol) mRNA were measured by RT
      PCR. Foxol protein in nuclear and cytoplasm were quantified by western blotting.
      RESULTS: Compared with control group, body weight, FPG, TG, TC, insulin and HOMA
      index in obese group were significantly increased. Octreotide treatment showed
      obviously reduced levels of the parameters. The plasma SST levels in the obese
      group tended to decrease compared with that in the control group (P >0. 05),
      while plasma SST levels was increased in the octreotide-treated group compared
      with that in the obese group (P <0. 05). Obese rats display more G6pase, Pepck
      and Foxol mRNA and higher ratio of nuclear Foxol protein to cytoplasm Foxol
      protein than control rats (P < 0. 01), whereas octreotide intervention reversed
      those changes (P <0. 01). CONCLUSION: The administration of octreotide can
      ameliorate abnormal enhancement of hepatic gluconeogenesis, which might be
      attributed to the reduced activity and expression of Foxol and then decreased
      expression levels of G6pase and Pepck mRNA.

PMID- 25997235
TI  - [Taurine inhibited the apoptosis of glial cells induced by hypoxia].
AB  - OBJECTIVE: To study the anti-apoptosis effect of taurine on hypoxic glial cells.
      METHODS: The glial cells were primarily cultured and divided into three groups,
      the control group, hypoxia group, and hypoxia + taurine group. The hypoxia model
      was established by putting cells in a tank filled with oxygen-free mixed gas (95%
      N2, 5% CO2) with oxygen concentration less than 1%. When the hypoxia time (6
      hours) was finished, taurine (3 mmol/L) was added to incubate for hypoxia +
      taurine group. Finally, the glial cells of all groups were collected for FCM and
      RT-PCR tests after 24 and 48 hours, respectively. RESULTS: The earlier apoptosis
      rate was (2. 48 +/- 0. 92) %, the middle-late apoptosis rate was (2. 97 +/- 0.
      75) % for 48h hypoxia group, they were significantly higher than the control
      group (1. 02 +/- 0. 44) % (P < 0. 05). The earlier apoptosis rate (1. 39 +/- 1.
      03) % and middle-late apoptosis rate (1. 62 +/- 0. 1) % for 48 h taurine group
      were significantly lower than the hypoxia group (P <0. 05). The relative
      expression level of Bax mRNA for hypoxia group increased by five times higher
      than the control group, and two times than the hypoxia + taurine group (P <0.
      05), and that of Bcl-2 mRNA for 48 h hypoxia + taurine group was two times higher
      than the hypoxia group (P <0. 01). The relative expression levels of HIF-lalpha
      mRNA for 24 h and 48 h hypoxia + taurine groups were significantly higher than
      the hypoxia group (P <0. 01). CONCLUSION: Taurine could obviously inhibited the
      apoptosis of glial cells induced by hypoxia.

PMID- 25997234
TI  - [Betaine-enriched beet suppresses hyperhomocysteinemia induced by choline
      deficiency in rats].
AB  - OBJECTIVE: To investigate the dose-dependent effects of beet powder
      supplementation on hyperhomocysteinemia induced by choline deprivation in rats.
      Methods 48 rats of the Wistar were fed 25% soybean protein diet (25S), choline
      deprivation in 25S diets (25SCD) with different betaine levels (0. 05% and 0. 1%)
      and beet powder levels (4. 12% and 8. 24%) corresponds to betaine levels for 10
      days, and they were killed by decapitation to obtain blood and livers was subject
      to analysis the concentration of homocysteine, cysteine and other amino acids, as
      well as BHMT and CBS activities. RESULTS: The homocysteine concentration was
      increased from (11. 8 +/- 0. 4) umol/L to (33. 2 +/- 0. 6) umol/L by choline
      deprived - 25S diets (P < 0. 05). The choline deprivation-induced enhancement of
      plasma homocysteine concentration in rats fed 25S diet was significantly
      suppressed by 0. 10% betaine or 8. 24% beet in a dose dependent manner.
      Supplementation with betaine or beet significant increased hepatic BHMT activity.
      CONCLUSION: The results indicated that betaine or beet could completely suppress
      the hyperhomocysteinemia induced by choline deficiency resulting from stimulating
      the homocysteine removal by both remethylation and cystathionine formation.

PMID- 25997236
TI  - [Uncertainty evaluation for determining ginsenosides in ginseng food by HPLC].
AB  - OBJECTIVE: To discuss the influencing factors for uncertainty and evaluate the
      measurement uncertainty for the determination of ginsenosides Rg1, Re, Rb1 and Rd
      in ginseng food by HPLC. METHODS: According to the regulation of JJF1059. 1 -
      2012, the components of uncertainty in the measuring process were studied and
      quantified for the calculation of combined uncertainties and expanded
      uncertainties. RESULTS: The expanded uncertainties for the HPLC determination of
      ginsenosides Rg1, Re, Rb1 and Rd were 0. 0766, 0. 0700, 0. 0628 and 0. 0722
      g/100g (k = 2) respectively from sample of Radix ginseng, and expanded
      uncertainties of ginsenosides Rg1, Re, Rb1 and Rd were 0. 0476, 0. 0672, 0. 0516
      and 0. 0514 g/100g(k = 2) from sample of Red ginseng. CONCLUSION: The uncertainty
      from pretreatment and standard curve fitting process were the main sources of
      uncertainty.

PMID- 25997237
TI  - [Determination of triclosan and triclocarban in human breast milk by solid-phase
      extraction and ultra performance liquid chromatography-tandem mass spectrometry].
AB  - OBJECTIVE: An analytical method was developed to simultaneously detect triclosan
      (TCS) and triclocarban (TCC) in human breast milk using solid-phase extraction
      (SPE) with ultra performance liquid chromatography-tandem mass spectrometry (UPLC
      MS/MS). METHODS: Samples were extracted by acetonitrile and purified with C -18
      SPE cartridge after enzymolysis with beta-glucuronidase/arylsulfatase. The
      chromatographic separation was performed on a Waters ACQUITY UPLCTM HSS T3 column
      (100 mm x 2. 1 mm, 1. 8 um) with gradient elution using methanol and water at a
      flow rate of 0. 3 ml/min. The target analytes were assayed by triple quadrupole
      mass spectrometer operating in the negative ion mode. Quantification was
      performed by isotopic internal standard calibration. RESULTS: Satisfactory
      linearity (r2 > 0. 999) was obtained over the range of 0. 2 - 20. 0 ug/L and 0.
      02 - 2. 0 ug/L for triclosan and triclocarban, respectively, with the limits of
      quantifications (LOQs) of 0. 41 and 0. 03 ug/kg. Average recoveries of two target
      compounds (spiked at three concentration levels) ranged from 100. 2% to 119. 3%,
      with the relative standard deviations (RSDs) between 5. 91% and 11. 31% (n =6).
      Twenty-five real samples (n = 25) were detected containing TCS and TCC at
      concentrations of < LOQ - 0. 77 ug/kg and < LOQ - 4. 28 ug/kg, respectively.
      CONCLUSION: Due to its high sensitivity and good reproductivity, this method can
      be applied to analyze TCS and TCC in human breast milk.

PMID- 25997238
TI  - [Determination of aniline in whole blood by using solid-phase extraction and high
      performance liquid chromatography with fluorescence detector].
AB  - OBJECTIVE: To establish a method for the determination of trace aniline in whole
      blood by using solid-phase extraction and high performance liquid chromatography
      with fluorescence detector. METHODS: After the whole blood was diluted by water,
      extracted by acetonitrile, cleaned and enriched by Cleanert NH2 solid-phase
      extraction (SPE) cartridge, separation was performed on a Kromasil C8 column(250
      mm x 4. 6 mm i. d., 5 lambdam) with the mobile phase of water/acetonitrile
      (20/80, V/V). Detection was carried out by fluorescence detector at ex 225 nm and
      lambdaem 335 nm. RESULTS: Calibration curve was linear in the range of 3. 0 -
      200.0 ug/L with a correlation coefficient of 0. 9992, and the limit of
      quantitation(LOQ) was 3. 0 ug/L. The extraction recoveries were 87. 5% - 104. 4%,
      and the intra-day and inter-day RSDs were 3. 1% - 6. 6% and 6. 4% - 8. 6%,
      respectively. CONCLUSION: The developed method is simple, fast, little
      interference, good specificity for the satisfactory determination of trace
      aniline in whole blood.

PMID- 25997239
TI  - [Determination of the migration of 16 PAHs from paper cups into food stimulants].
AB  - OBJECTIVE: To study the variation of the residual polycyclic aromatic
      hydrocarbons (PAHs) from disposable paper cups into different food stimulants
      with time. METHODS: The disposable paper cups were soaked with water, 4% acetic
      acid, 20% ethanol and hexane respectively, and the 16 PAHs were extracted with
      CH2Cl2, and then determined by gas chromatography-mass spectrometry (GC-MS).
      RESULTS: The residual PAHs from disposable paper cups could be leached from the
      four stimulants, and the amounts increased with the increase of time. The mainly
      PAHs extracts were phenathrene, pyrene, naphthalene, anthracene and fluorene with
      lower molecular weight. Largest leaching ability of hexane was observed.
      CONCLUSION: The supervision of disposable paper cups should be strengthened and
      it should be avoided using for prolonged immersion.

PMID- 25997240
TI  - [Determination of 8 elements in food by inductively coupled plasma optical
      emission spectrometer simultaneously].
AB  - OBJECTIVE: To establish a method for determination of 8 elements including K, Na,
      Ca, Mg, Fe, Zn, Cu and Mn in food by inductively coupled plasma optical emission
      spectrometer (ICP-OES). METHODS: After high-pressure digestion by HNO3 in closed
      vessel, 8 elements were simultaneously determined by ICP-OES. RESULTS: The
      detection limits of 8 elements ranged from 0. 02 to 6 mg/kg(solid samples), 0.
      005 mg/L to 2 mg/L(liquid samples). The average correlation coefficients were;
      >=0. 999 with good linearity. The precision ranged from 0. 1% to 9. 6%, the
      recoveries ranged from 88% to 115%. The results of analyzing standard materials
      were in the certificate values. CONCLUSION: The method is rapid and accurate with
      less interference which meets the technical requirements of food testing and can
      be applied to the determination of 8 elements in food simultaneously.

PMID- 25997241
TI  - [Meta-analysis of relationship between maternal formaldehyde exposure during
      pregnancy and spontaneous abortion].
AB  - OBJECTIVE: To evaluate the relationship between maternal formaldehyde exposure
      during pregnancy and spontaneous abortion. METHODS: A computerized literature
      search was carried out to collect articles published before 2014. The study types
      included case-control and cohort studies. And then the statistical analysis was
      conducted by using RevMan 5. 1 software. RESULTS: A total of 6 studies were
      included in Meta-analysis (totally 666 subjects and 3087 controls) according to
      the selection criteria. Because all the studies selected were homogeneous (I2 =
      37% , P = 0. 16) , the fixed effect model was used for calculation of the
      combined OR values. Compared with the control, maternal formaldehyde exposure
      during pregnancy was significantly associated with spontaneous abortion (OR = 1.
      64, 95% CI 1. 20 - 2. 24, P = 0. 002). CONCLUSION: Maternal formaldehyde exposure
      during pregnancy may increase the risk of spontaneous abortion.

PMID- 25997242
TI  - [Comparison among various software for LMS growth curve fitting methods].
AB  - OBJECTIVE: To explore the methods to realize the growth curve fitting of
      coefficients of skewness-median-coefficient of variation (LMS) using different
      software, and to optimize growth curve statistical method for grass-root child
      and adolescent staffs. METHODS: Regular physical examination data of head
      circumference for normal infants aging 3, 6, 9 and 12 months in Baotou City were
      analyzed. Statistical software such as SAS, R, STATA and SPSS were used to fit
      the LMS growth curve and the results were evaluated upon the user 's convenience,
      study circle, user interface, results display forms, software update and
      maintenance and so on. RESULTS: Growth curve fitting results showed the same
      calculation outcome and each of statistical software had its own advantages and
      disadvantages. With all the evaluation aspects in consideration, R software
      excelled others in LMS growth curve fitting. CONCLUSION: R software have the
      advantage over other software in grass roots child and adolescent staff.

PMID- 25997243
TI  - [Energy and macronutrients intake from pre-packaged foods among urban residents].
AB  - OBJECTIVE: To analyze the energy and macronutrients intake from pre-packaged
      foods among urban residents in China. METHODS: The adult subjects were selected
      from 9 cities of Beijing, Shanghai, Chongqing, Shenyang, Harbin, Jinan,
      Zhengzhou, Changsha, Nanning. The recording method for 7 consecutive days was
      used to collect pre-packaged foods consumption information. RESULTS: Among
      subjects, the median intake of energy, protein, fat and carbohydrate from pre
      packaged foods were 628. 8kJ/d, 5.0 g/d, 6.7 g/d and 17.0 g/d, respectively.
      Among consumers, the median intake of energy, protein, fat and carbohydrate from
      pre-packaged foods were 745. 3 kJ/d, 6. 0 g/d, 7. 7 g/d and 20. 7 g/d,
      respectively. CONCLUSION: The energy and macronutrients intake from pre-packaged
      foods were at low level.

PMID- 25997244
TI  - Chitosan gel formulations containing egg yolk oil and epidermal growth factor for
      dermal burn treatment.
AB  - In the present study chitosan based gel formulations containing Egg Yolk Oil
      (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at
      enhanced topical treatment of dermal burns the combination of traditional
      approaches with modern drug delivery systems. Physicochemical properties of the
      formulations were analyzed and efficacy of the formulations prepared were
      evaluated versus a commercial product; Silverdin (1% silver sulfadiazine) in vivo
      on Wistar rats. Burns were generated on the back of the rats and at predetermined
      time intervals tissue samples were collected and evaluated histologically. The
      analyses showed that chitosan based gel formulations containing Egg Yolk Oil (E1)
      and chitosan based gel formulations containing EYO and EGF (M1) formulations seem
      to be better alternatives for Silverdin with a significant difference (p < 0.05)
      considering healing ranks of tissue samples.

PMID- 25997245
TI  - Pharmacokinetics of loxoprofen and its active metabolite after dermal application
      of loxoprofen gel to rats.
AB  - This study was conducted to evaluate the pharmacokinetics of loxoprofen (LX) and
      its active metabolite (trans-OH form) after a single dermal application of LX gel
      (LX-G) to rats. In the skin at the treated site, generation of the trans-OH form
      was detected and both LX and the trans-OH form remained at high concentrations
      for 24 h after dermal application. Furthermore, both LX and the trans-OH form
      also remained in the skeletal muscle over 24 h after the single dermal
      application, while they eliminated rapidly after the single oral administration.
      The area under the curve up to the last measurable point (AUC(0-t)) for plasma
      concentrations of LX or the trans-OH form after dermal application of LX-G was
      less than 11% of that after oral administration of LX. In addition, C(max) and
      AUC(0-t) increased in a saturable manner while increasing the dose. Overall,
      these results demonstrated that the trans-OH form was generated at the treated
      site with the process of dermal absorption of LX and it remained at the target
      site for a long period with low systemic exposure compared to oral
      administration.

PMID- 25997246
TI  - RIP-V improves murine survival in a sepsis model by down-regulating RNAIII
      expression and alpha-hemolysin release of methicillin-resistant Staphylococcus
      aureus.
AB  - Staphylococcus aureus is associated with serious invasive infections and high
      mortality rates due to a large number of toxins released. The persistent
      increasing resistance of S. aureus has driven the need for new anti-infection
      agents and innovative therapeutic strategies. RNAIII-inhibiting peptide (RIP) has
      been reported to reduce bacterial virulence by interfering with S. aureus quorum
      sensing system. The present study aimed to investigate whether two new RIP
      derivatives (RIP-V and RIP-L) could improve the survival rate of mice in a MRSA
      sepsis model. We found that neither anti-bacterial nor cell toxicity were
      displayed by all RIPs in vitro. In vivo protective effects were observed using a
      MRSA-induced mice sepsis model. Among RIPs, RIP-V exhibited the strongest
      protection function on mice survival and inhibition of pathological damages. Our
      studies firstly verified that RIPs could inhibited the RNAIII expression of S.
      aurues isolated from liver tissue of BALB/c mice. Moreover, RIP-V exhibited the
      strongest inhibitory effect on RNAIII and can decrease markedly the secretion of
      o-hemolysin in liver. These findings indicate that RIP-V might be considered as a
      potential and specific drug candidate for treating S. aureus infections,
      especially for MRSA.

PMID- 25997247
TI  - The role of CGRP and CALCA T-692C single-nucleotide polymorphism in psoriasis
      vulgaris.
AB  - Calcitonin gene related protein (CGRP) is increased in both lesional and non
      lesional psoriasis. The role of CGRP in the pathogenesis of psoriasis vulgaris is
      still not clear. We designed to determine the CGRP-I (or CALCA), II (or CALCB)
      gene expression and morbidity and CALCA T-692C single-nucleotide polymorphism
      (SNP). Peripheral blood mononuclear cells (PBMCs) and plasma samples were
      collected, and CGRP level and CGRP-I, II mRNA expression were measured in
      psoriasis patients and healthy controls. The CALCA T-692C genetic polymorphism in
      psoriasis and control subjects was also compared. A higher expression of CGRP-I,
      II mRNA in PBMCs in psoriasis patients. The plasma CGRP level in psoriasis
      patients was also higher than that in healthy subjects. SNP analysis showed
      carriers of the T-692C allele were over-represented in non-drinking Patients. The
      plasma CGRP level was higher in alcohol-drinking patients with TT genotype than
      that with TC genotype. The plasma CGRP level is increased in psoriasis patients
      and CALCA T-692C polymorphism TT genotype is a factor for the affectability in
      alcohol-drinking Psoriasis vulgaris patients.

PMID- 25997248
TI  - UGT1A1*28 polymorphism influences glucuronidation of bazedoxifene.
AB  - Bazedoxifene is used for the prevention and treatment of osteoporosis. After
      peroral application, bazedoxifene is metabolized by UDP-glucuronosyltransferases
      (UGTs) to bazedoxifene-4'-glucuronide (M4) and bazedoxifene-5-glucuronide (M5).
      It has already been shown that a relatively common UGT1A1*28 polymorphism can
      considerably affect raloxifene pharmacokinetics and pharmacodynamics. As
      pharmacokinetics of bazedoxifene and raloxifene are very similar, the influence
      of UGT1A1*28 polymorphism on metabolism of bazedoxifene was investigated by
      genotyped microsomes. Our results indicate an influence of UGT1A1*28 allele on
      the formation clearance of both bazedoxifene metabolites. The decreased metabolic
      clearance was most pronounced in microsomes from polymorphic homozygote (*28/*28)
      where a 7 to 10-fold lower metabolic clearance was observed for both metabolites
      compared to other genotypes. In conclusion, the significant UGT1A1*28 genotype
      effect on bazedoxifene intrinsic metabolic clearance indicates that this subject
      is worth further exploration in vivo and provides valuable information research
      in this field.

PMID- 25997249
TI  - ABCB1 hypomethylation is associated with decreased antiplatelet effects of
      clopidogrel in Chinese ischemic stroke patients.
AB  - Current predictive models including the CYP2C19 polymorphism and clinical factors
      still explain only about 12% of variability of clopidogrel responsiveness. Up
      until recently, the precise mechanism of clopidogrel resistance remains unclear.
      P-glycoprotein (P-gp) encoded by ABCB1, a transmembrane calcium-dependent efflux
      pump for clopidogrel, implicated a role in clopidogrel resistance. In this
      present study, we investigated the methylation status of ABCB1 gene promoter in
      relation to ABCB1 mRNA expressions and the antiplatelet effects of clopidogrel.
      This study was a prospective cohort analysis of eligible stroke patients (n =
      183, aged 18-75 years) who received clopidogrel (75 mg/day) for at least 5 days
      before discharge. A final subcohort of 87 patients with CYP2C19*1/*1 genotype
      were enrolled in the study population. Patients were grouped in quartiles of
      maximum platelet aggregation (MPA values (Q1, Q2, Q3 and Q4, MPA(Q1) < 14.1%,
      MPA(Q4) > 35.4%). The methylation status of the ABCB1 promoter was 1.8 times in
      the Q1 MPA group (10.1 +/- 2.4%) than in the Q4 MPA group (5.5 +/- 2.1%) (P <
      0.001). ABCB1 methylation correlated inversely with MPA (R = - 0.764, P < 0.001)
      and mRNA expression (R = - 0.839, P < 0.001). Results of a multivariate linear
      regression model demonstrated that ABCB1 methylation was independently associated
      with MPA (beta(coef ficient) = - 4.71, P < 0.001). ABCB1 expression was 0.62
      times in the Q1 MPA group (5.3 +/- 1.4 per thousand) than in the Q4 MPA (8.5 +/-
      2.5%o), and the expression of ABCB1 correlated positively with ADP-induced MPA (R
      = 0.791, P < 0.001). ABCB1 promoter methylation status in whole blood appears to
      be inversely associated with ABCB1 mRNA expressions and MPA. In conclusions,
      hypomethylation of ABCB1 promoter is associated with a decreased response to
      clopidogrel in ischemic stroke patients via increased ABCB1 mRNA expression.

PMID- 25997250
TI  - Propofol attenuation of hydrogen peroxide-induced injury in human umbilical vein
      endothelial cells involves aldose reductase.
AB  - Propofol is a widely used intravenous anesthetic agent with
      antioxidant/antiapoptotic properties. Aldose reductase (AR) has been implicated
      in oxidative stress and apoptosis in endothelial cells. AR inhibition may protect
      cells from cardiovascular injury. Although the cytoprotective effect of propofol
      against hydrogen peroxide (H2O2)-induced injury has been widely studied, there is
      no information about the effects of propofol on AR. We therefore investigated the
      effect of propofol on H2O2-mediated injury and on aldose reductase expression. We
      found that propofol protected HUVECs against H2O2-induced damage and apoptosis
      and ameliorated AR expression induced by H2O2. Propofol also inhibited H2O2
      induced p38 MAPK, JNK and Akt phosphorylation. Epalrestat (an AR inhibitor) or
      ablation of AR siRNA had a similar effect to propofol. The results suggest that
      propofol may be a preemptive anesthetic in patients with cardiovascular disease
      and inhibition of AR might be a new cytoprotective pathway for propofol.

PMID- 25997251
TI  - The efficacy of placebo-adjusted taspoglutide on body weight reduction in
      clinical trials.
AB  - Taspoglutide has elicited a long-lasting glycemic control effect with favorable
      body weight loss. The objective of this study was to develop a quantitative model
      to delineate the net efficacy of taspoglutide on body weight (WT) loss from the
      response of placebo in type 2 diabetes patients, and further find pharmacodynamic
      potency of taspoglutide for half of maximum reduction response of WT. Several PD
      data about taspoglutide treatments for type 2 diabetes patients were digitalized
      from the published papers. The model based metaanalysis (MBMA) study for WT loss
      was performed with Monolix 4.3 software. The MBMA successfully described the
      effects of placebo and taspoglutide on the pharmacological index of WT loss in
      clinical trials. The pharmacodynamic potency (41.7 pmol/l) produced 50% of
      maximum response of WT (-1.85 kg) from the responses of placebo (-1.33 kg). The
      longitudinal MBMA could be utilized to quantitatively describe the efficacy of
      taspoglutide on body weight loss and may lead to a clinical guideline for
      treatment of type 2 diabetes patients in the future.

PMID- 25997252
TI  - Synergistic antitumor activity of vitamin D3 combined with metformin in human
      breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.
AB  - Metformin is usually used for the treatment of type 2 diabetes. Recently, many
      studies suggest that metformin and vitamin D have broad-spectrum antitumor
      activities. Our aim in this research was to study the effects of vitamin D3
      combined with metformin on the apoptosis induction and its mechanisms in the
      human breast cancer cell line MDA-MB-231. Cell proliferation was measured by
      methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was
      observed after Hoechst 33342 staining. Here we show that vitamin D3 280 MUg/ml or
      vitamin D3 300 MUg/ml or vitamin D3 320 MUg/ml seperately combined with metformin
      15000 MUg/ml exhibited synergistic effects on cell proliferation and apoptosis.
      The underlying anti-tumor mechanisms may involve m-TOR related pathways, which
      are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as
      well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p
      S6.

PMID- 25997253
TI  - Vitamin D3 enhances antitumor activity of metformin in human bladder carcinoma SW
      780 cells.
AB  - OBJECTIVE: To study the effects of vitamin D3 combined with metformin on the
      proliferation and apoptosis in human bladder cancer cell line SW-780 and its
      possible mechanism. METHODS: MTT assay and fluorescence microscope observations
      were used to study the effects of vitamin D3 combined with metformin on the
      proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to
      detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c
      Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P70S6K,
      p-S6. RESULTS: MTT results showed that 320 MUg/ml vitamin D3 combined with 620
      MUg/ml metformin acting on cells for 48h had a significant synergistic effect on
      proliferation. Fluorescence microscope observations showed that compared with
      negative control group and monotherapy treatment group, the apoptosis features of
      combination treatment group were obvious and the apoptosis rate increased
      greatly. Western blot showed that compared with the negative control group and
      monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D1 and c
      Myc in combination treatment group significantly decreased, whereas the
      expression level of Bax significantly increased, and the expression levels of p
      IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly
      decreased. CONCLUSION: Vitamin D3 combined with metformin exhibited obvious
      inhibitory effects on the cell proliferation and apoptosis induction in SW-780
      cells. The underlying anti-tumor mechanism might be related to inhibiting the
      expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and
      activating the expression of Bax.

PMID- 25997254
TI  - Effect of gabazine on sensory stimulation train evoked response in mouse
      cerebellar Purkinje cells.
AB  - Cerebellar Purkinje cells (PCs) respond to sensory stimulation via climbing fiber
      and mossy fiber-granule cell pathways, and generate motor-related outputs
      according to internal rules of integration and computation. However, the dynamic
      properties of sensory information processed by PC in mouse cerebellar cortex are
      currently unclear. In the present study, we examined the effects of the gamma
      aminobutyric acid receptor A (GABA(A)) antagonist, gabazine, on the stimulation
      train on the simple spike firing of PCs by electrophysiological recordings
      method. Our data showed that the output of cerebellar PCs could be significantly
      affected by all pulses of the low-frequency (0.25 -2 Hz) sensory stimulation
      train, but only by the 1st and 2nd pulses of the high-frequency (>= 4 Hz) sensory
      stimulation train. In the presence of gabazine (20 MUM), each pulse of 1 Hz
      facial stimulation evoked simple spike firing in the PCs, but only the 1st and
      2nd pulses of 4 Hz stimulation induced an increase in simple spike firing of the
      PCs. These results indicated that GABAA receptor-mediated inhibition did not
      significantly affect the frequency properties of sensory stimulation evoked
      responses in the mouse cerebellar PCs.

PMID- 25997255
TI  - Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var.
      hainanensis Tsiang increase LkappaB-alpha expression and ameliorate ulcerative
      colitis.
AB  - The therapeutic potential of pectic polysaccharides extracted from Rauvolfia
      verticillata (Lour.) Baill. var. hainanensis Tsiang in ulcerative colitis were
      investigated. This study showed that pectic polysaccharides extracted from
      Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang ameliorated
      ulcerative colitis and were proposed to exhibit anti-inflammatory effects via
      increased expression of IkappaB-alpha proteins and suppressing NF-alphaB
      translocation.

PMID- 25997256
TI  - One hundred years of the history of pharmacy studies in Turkey.
AB  - As an inheritor of the rich medico-pharmaceutical heritage in Asia Minor, Turkey
      constituted a critical junction of exchange and dissemination of pharmacy
      knowledge between East and West throughout history. This greatly contributed to
      the rapid development of pharmacy as an established profession. The 20th century
      saw scholarly examination of the field's history: the first book on the history
      of pharmacy appeared in Turkish (1911); a history of pharmacy course was offered
      for the first time in the pharmacy curriculum (1945); the first history of
      pharmacy museum was founded (1960); and national conferences on the history of
      pharmacy were launched (1990). In addition to providing information on the
      milestones of the history of pharmacy studies in Turkey in the last hundred
      years, this study aims to statistically evaluate the change in the number of
      history of pharmacy-related publications per decade as well as discuss the
      current situation of history of pharmacy education at Turkish universities. The
      history of pharmacy has become a stronger and more independent academic
      discipline in Turkey, particularly in the last two decades. As of 2014, history
      of pharmacy undergraduate courses are taught at all faculties of pharmacy in
      Turkey, except the Yuzuncu Yil University (Van), mainly between first and fourth
      semesters.

PMID- 25997257
TI  - [The blind source separation method based on self-organizing map neural network
      and convolution kernel compensation for multi-channel sEMG signals].
AB  - A new method based on convolution kernel compensation (CKC) for decomposing multi
      channel surface electromyogram (sEMG) signals is proposed in this paper.
      Unsupervised learning and clustering function of self-organizing map (SOM) neural
      network are employed in this method. An initial innervations pulse train (IPT) is
      firstly estimated, some time instants corresponding to the highest peaks from the
      initial IPT are clustered by SOM neural network. Then the final IPT can be
      obtained from the observations corresponding to these time instants. In this
      paper, the proposed method was tested on the simulated signal, the influence of
      signal to noise ratio (SNR), the number of groups clustered by SOM and the number
      of highest peaks selected from the initial pulse train on the number of
      reconstructed sources and the pulse accuracy were studied, and the results show
      that the proposed approach is effective in decomposing multi-channel sEMG
      signals.

PMID- 25997258
TI  - [Brain function network analysis and recognition for psychogenic non-epileptic
      seizures based on resting state electroencephalogram].
AB  - Studies have shown that the clinical manifestation of patients with
      neuropsychiatric disorders might be related to the abnormal connectivity of brain
      functions. Psychogenic non-epileptic seizures (PNES) are different from the
      conventional epileptic seizures due to the lack of the expected
      electroencephalographically epileptic changes in central nervous system, but are
      related to the presence of significant psychological factors. Diagnosis of PNES
      remains challenging. We found in the present work that the connectivity between
      the frontal and parieto-occipital in PNES was weaker than that of the controls by
      using network analysis based on electroencephalogram (EEG) signals. In addition,
      PNES were recognized by using the network properties as linear discriminant
      nalysis (LDA) input and classification accuracy was 85%. This study may provide a
      feasible tool for clinical diagnosis of PNES.

PMID- 25997259
TI  - [Analysis of anesthesia characteristic parameters based on the EEG signal].
AB  - All the collected original electroencephalograph (EEG) signals were the subjects
      to low-frequency and spike noise. According to this fact, we in this study
      performed denoising based on the combination of wavelet transform and independent
      component analysis (ICA). Then we used three characteristic parameters,
      complexity, approximate entropy and wavelet entropy values, to calculate the
      preprocessed EEG data. We then made a distinguishing judge on the EEG state by
      the state change rate of the characteristic parameters. Through the anesthesia
      and non-anesthesia EEG data processing results showed that each of the three
      state change rates could reach about 50.5%, 21.6%, 19.5%, respectively, in which
      the performance of wavelet entropy was the highest. All of them could be used as
      a foundation in the quantified research of depth of anesthesia based on EEG
      analysis.

PMID- 25997260
TI  - [A novel method of multi-channel feature extraction combining multivariate
      autoregression and multiple-linear principal component analysis].
AB  - Brain-computer interface (BCI) systems identify brain signals through extracting
      features from them. In view of the limitations of the autoregressive model
      feature extraction method and the traditional principal component analysis to
      deal with the multichannel signals, this paper presents a multichannel feature
      extraction method that multivariate autoregressive (MVAR) model combined with the
      multiple-linear principal component analysis (MPCA), and used for
      magnetoencephalography (MEG) signals and electroencephalograph (EEG) signals
      recognition. Firstly, we calculated the MVAR model coefficient matrix of the
      MEG/EEG signals using this method, and then reduced the dimensions to a lower
      one, using MPCA. Finally, we recognized brain signals by Bayes Classifier. The
      key innovation we introduced in our investigation showed that we extended the
      traditional single-channel feature extraction method to the case of multi-channel
      one. We then carried out the experiments using the data groups of IV-III and IV -
      I. The experimental results proved that the method proposed in this paper was
      feasible.

PMID- 25997261
TI  - [Robustness analysis of adaptive neural network model based on spike timing
      dependent plasticity].
AB  - To explore the self-organization robustness of the biological neural network, and
      thus to provide new ideas and methods for the electromagnetic bionic protection,
      we studied both the information transmission mechanism of neural network and
      spike timing-dependent plasticity (STDP) mechanism, and then investigated the
      relationship between synaptic plastic and adaptive characteristic of biology.
      Then a feedforward neural network with the Izhikevich model and the STDP
      mechanism was constructed, and the adaptive robust capacity of the network was
      analyzed. Simulation results showed that the neural network based on STDP
      mechanism had good rubustness capacity, and this characteristics is closely
      related to the STDP mechanisms. Based on this simulation work, the cell circuit
      with neurons and synaptic circuit which can simulate the information processing
      mechanisms of biological nervous system will be further built, then the
      electronic circuits with adaptive robustness will be designed based on the cell
      circuit.

PMID- 25997262
TI  - [A nonlinear multi-compartment lung model for optimization of breathing airflow
      pattern].
AB  - It is difficult to select the appropriate ventilation mode in clinical mechanical
      ventilation. This paper presents a nonlinear multi-compartment lung model to
      solve the difficulty. The purpose is to optimize respiratory airflow patterns and
      get the minimum of the work of inspiratory phrase and lung volume acceleration,
      minimum of the elastic potential energy and rapidity of airflow rate changes of
      expiratory phrase. Sigmoidal function is used to smooth the respiratory function
      of nonlinear equations. The equations are established to solve nonlinear boundary
      conditions BVP, and finally the problem was solved with gradient descent method.
      Experimental results showed that lung volume and the rate of airflow after
      optimization had good sensitivity and convergence speed. The results provide a
      theoretical basis for the development of multivariable controller monitoring
      critically ill mechanically ventilated patients.

PMID- 25997263
TI  - [Effects of the first metatarsophalangeal joint bending on human walking gait
      stability when walking on slippery floor].
AB  - The first metatarsophalangeal joint bending plays an important role in the foot
      movement. However, the existing researches mainly focused on the movement scope
      of the joint and the clinical treatments of related foot diseases. In order to
      investigate the effects of the first metatarsophalangeal joint bending on human
      walking gait stability, the present researchers recruited 6 healthy young men to
      perform the first metatarsophalangeal joint constraint (FMJC) and barefoot (BF)
      walking tests. Data of the temporal and spatial parameters, the joint angles of
      lower limbs, the ground reaction forces (GRF) and utilized coefficients of
      friction (UCOF) were collected and analyzed. The results showed that, since hip
      and knee could produce compensation motions, the FMJC had no significant effects
      on waking gait, but the slip and fall probability increased significantly.

PMID- 25997264
TI  - [Analysis and computational fluid dynamics simulation of hemodynamic influences
      caused by splenic vein thrombosis].
AB  - This paper aims to analyze the impact of splenic vein thrombosis (SVT) on the
      hemodynamic parameters in hepatic portal vein system. Based on computed
      tomography (CT) images of a patient with portal hypertension and commercial
      software MIMICS, the patient's portal venous system model was reconstructed.
      Color Doppler ultrasound method was used to measure the blood flow velocity in
      portal vein system and then the blood flow velocities were used as the inlet
      boundary conditions of simulation. By using the computational fluid dynamics
      (CFD) method, we simulated the changes of hemodynamic parameters in portal venous
      system with and without splenic vein thrombosis and analyzed the influence of
      physiological processes. The simulation results reproduced the blood flow process
      in portal venous system and the results showed that the splenic vein thrombosis
      caused serious impacts on hemodynamics. When blood flowed through the thrombosis,
      blood pressure reduced, flow velocity and wall shear stress increased. Flow
      resistance increased, blood flow velocity slowed down, the pressure gradient and
      wall shear stress distribution were more uniform in portal vein. The blood supply
      to liver decreased. Splenic vein thrombosis led to the possibility of forming new
      thrombosis in portal vein and surroundings.

PMID- 25997265
TI  - [Biomechanical study of lumbar spine under different vibration conditions].
AB  - We observed the effect of vibration parameters on lumbar spine under different
      vibration conditions using finite element analysis method in our laboratory. In
      this study, the CT-images of L1-L5 segments were obtained. All images were used
      to develop 3D geometrical model using the Mimics10. 01 (Materialise, Belgium).
      Then it was modified using Geomagic Studio12. 0 (Raindrop Geomagic Inc. USA).
      Finite element (FE) mesh model was generated by Hypermesh11. 0 (Altair
      Engineering, Inc. USA) and Abaqus. Abaqus was used to calculate the stress
      distribution of L1-L5 under different vibration conditions. It was found that in
      a vibration cycle, tensile stress was occurred on lumbar vertebra mainly. Stress
      distributed evenly and stress concentration occurred on the left rear side of the
      upper endplate. The stress had no obvious changes under different frequencies,
      but the stress was higher when amplitude was greater. In conclusion, frequency
      and amplitude parameters have little effect on the stress distribution in
      vertebra. The stress magnitude is positively correlated with the amplitude.

PMID- 25997266
TI  - [Effects of intervertebral disc degeneration on biomechanics behavior
      characteristics of L4-L5 under the vertical load].
AB  - A geometrical model of L4-L5 lumbar segment was constructed using a three
      dimensional graphics software. Four conditions of the degenerated discs, i. e.
      light degeneration, moderate degeneration, severe degeneration and complete
      excision degeneration, were simulated with loading situations using finite
      element method under the condition of appropriate computational accuracy. By
      applying a vertical load of 378.93 N on L4 vertebral plate, stress nephograms on
      joint isthmus under four different working conditions were obtained. The results
      showed that the contacted area of facet joint was influenced by the degree of
      intervertebral disc degeneration level, which influenced the mises stress on
      joint isthmus. It was proved that joint isthmus was the important pressure-proof
      structure of the back of lumbar vertebra, and the stress values and distribution
      were related to structural stiffness of the back of lumbar vertebra as well as
      the contact area of facet joint. The conclusion could be the theoretical
      reference for the analysis of spinal biomechanics and artificial disc replacement
      as well.

PMID- 25997268
TI  - [Biomechanical research of transforaminal lumbar interbody fusion model].
AB  - Based on the surgical model using transforaminal lumbar interbody fusion (TLIF)
      to treat lumbar spondylolisthesis, this paper presents the investigations of the
      biomechanical characteristics of cage and pedicle screw in lumbar spinal fusion
      implant fixed system under different combinations with finite element method.
      Firstly, combining the CT images with finite element pretreatment software, we
      established three dimensional nonlinear finite element model of human lumbar L4
      L5 segmental slight slippage and implant under different fixed combinations. We
      then made a comparison analysis between the biomechanical characteristics of
      lumbar motion range, stress distribution of cage and pedicle screw under six
      status of each model which were flexion, extension, left lateral bending, right
      lateral bending, left axial rotation and right axial rotation. The results showed
      that the motion ranges of this model under different operations were reduced
      above 84% compared with those of the intact model, and the stability of the
      former was improved significantly. The stress values of cage and pedicle screw
      were relatively larger when they were fixed by single fusion device additional
      unilateral pedicle screw, but there was no statistically significant difference.
      The above research results would provide reference and confirmation for further
      biomechanics research of TLIF extracorporal specimens, and finally provide
      biomechanical basis for the feasibility of unilateral internal fixed diagonal
      intervertebral fusion TLIF surgery.

PMID- 25997267
TI  - [Optimal solution and analysis of muscular force during standing balance].
AB  - The present study was aimed at the optimal solution of the main muscular force
      distribution in the lower extremity during standing balance of human. The
      movement musculoskeletal system of lower extremity was simplified to a physical
      model with 3 joints and 9 muscles. Then on the basis of this model, an optimum
      mathematical model was built up to solve the problem of redundant muscle forces.
      Particle swarm optimization (PSO) algorithm is used to calculate the single
      objective and multi-objective problem respectively. The numerical results
      indicated that the multi-objective optimization could be more reasonable to
      obtain the distribution and variation of the 9 muscular forces. Finally, the
      coordination of each muscle group during maintaining standing balance under the
      passive movement was qualitatively analyzed using the simulation results
      obtained.

PMID- 25997269
TI  - [Fatigue property analysis of prosthesis of hip joint with two different
      materials].
AB  - Total hip replacement (THR) is replacing the prosthesis stem similar to human
      bone that takes advantage of the material with both good mechanical properties
      and biocompatibility to the damaged articular surface. Thus it can not only
      alleviate or even eliminate the pain but also effectively maintain the joint
      stability and freedom and restore its normal performance. Finite element analysis
      was used in this study to establish a 3D model of artificial hip stem, and
      explore its fatigue properties of different materials to ensure the safety and
      reliability. The calculating obtained two results of different metal hip
      prosthesis, including lifetime and deformation. The minimum service life of
      titanium prosthesis reaches 568 million times, which satisfies ISO standards,
      while the stainless steel does not suit to be a prosthesis material.

PMID- 25997270
TI  - [Research on the mechanical properties of bone scaffold reinforced by magnesium
      alloy/bioceramics composite with stereolithography double channels].
AB  - Focusing on the poor mechanical strength of porous bioceramics bone scaffold, and
      taking into account of the good mechanical properties of biodegradable magnesium
      alloy, we proposed a novel method to fabricate magnesium alloy/bioceramics
      composite bone scaffold with stereolithography double channels. Firstly, a
      scaffold structure without mutually connected double channels was designed. Then,
      an optimized bioceramics scaffold was fabricated according to stereolithography
      and gel-casing. Molten AZ31 magnesium alloy was perfused into the secondary
      channel of scaffold by low-pressure casting, and magnesium alloy/bioceramics
      composite bone scaffold was obtained when magnesium alloy was solidified. The
      compression test showed that the strength of bioceramics scaffold with only one
      channel and without magnesium alloy was (9.76 +/- 0.64) MPa, while the strength
      of magnesium alloy/bioceramics composite scaffold with double channels was (17.25
      +/- 0.88) MPa. It can be concluded that the magnesium alloy/bioceramics composite
      is obviously able to improve the scaffold strength.

PMID- 25997271
TI  - [Method of detection of negative terminology in Chinese electronic medical
      record].
AB  - The method for detecting the negative terms in Chinese electronic medical record
      (EMR) is useful in providing evidence for constructing concept index. In this
      respect, we adopted an improved method which combined maximum matching with
      mutual information in order to extract terms in EMRs. This method can overcome
      the influence of overlay ambiguity. In addition, for the determination of
      negative semantic, we also adopted an improved method which combined rule-based
      method with word co-occurrence. This new method can reduce the probability of
      appearance of false positive terms caused by punctuation input errors. The result
      showed that the negative predictive value is 7.85% higher than the rule-based
      method.

PMID- 25997272
TI  - [Design of the remote monitoring system of vital sign based on smartphone and
      mobile internet].
AB  - The present paper presents the design of a remote monitoring system based on
      smartphone and mobile internet. The system can realize functions such as multi
      physiological parameter collection, micromation of collecting equipment, real
      time monitoring, remote data transmission, automatic alarm, physiological
      parameter analyze and Global Position System (GPS) location of patient's
      position. Besides acting as a receiver and transmission platform, smartphone can
      also process and analyze the physiological parameters, such as detection of the
      apnea from electrocardiogram (ECG). The system contains technologies of MCU,
      Bluetooth transmission, Android and Wed development, wavelet transform, mobile
      communication as a whole. It propels further developments of the remote mobile
      medical based on smartphone.

PMID- 25997273
TI  - [Cluster ensemble algorithm based on dual neural gas applied to cancer gene
      expression profiles].
AB  - The microarray technology used in biological and medical research provides a new
      idea for the diagnosis and treatment of cancer. To find different types of cancer
      and to classify the cancer samples accurately, we propose a new cluster ensemble
      framework Dual Neural Gas Cluster Ensemble (DNGCE), which is based on neural gas
      algorithm, to discover the underlying structure of noisy cancer gene expression
      profiles. This framework DNGCE applies the neural gas algorithm to perform
      clustering not only on the sample dimension, but also on the attribute dimension.
      It also adopts the normalized cut algorithm to partition off the consensus matrix
      constructed from multiple clustering solutions. We obtained the final accurate
      results. Experiments on cancer gene expression profiles illustrated that the
      proposed approach could achieve good performance, as it outperforms the single
      clustering algorithms and most of the existing approaches in the process of
      clustering gene expression profiles.

PMID- 25997274
TI  - [IC-kmedoids: a clustering algorithm for RNA secondary structure prediction].
AB  - Due to the minimum free energy model, it is very important to predict the RNA
      secondary structure accurately and efficiently from the suboptimal foldings.
      Using clustering techniques in analyzing the suboptimal structures could
      effectively improve the prediction accuracy. An improved k-medoids cluster method
      is proposed to make this a better accuracy with the RBP score and the incremental
      candidate set of medoids matrix in this paper. The algorithm optimizes initial
      medoids through an expanding medoids candidate sets gradually. The predicted
      results indicated this algorithm could get a higher value of CH and significantly
      shorten the time for calculating clustering RNA folding structures.

PMID- 25997275
TI  - [Effect of fluid shear stress on the cellular morphology and tight junction of
      laryngeal squamous carcinoma Hep2 cells].
AB  - This paper is aimed to investigate the effect of fluid shear stress on the tight
      junction of laryngeal squamous carcinoma (Hep2) cells and to explore the
      potential molecular mechanism. Hep2 cells were selected and subjected to the
      fluid shear stress of 1.4 dyn/cm2 for different time, respectively. The
      morphological changes of Hep2 cells under shear stress were observed using
      inverted microscope. The cell-cell junctions were examined by transmission
      electron microscope (TEM). The expressions of tight junction proteins (including
      Occludin, Claudin-5 and ZO-1) and the distribution of Claudin-5 were examined by
      Western blot assay and laser scanning confocal microscope, respectively. The
      results indicated that Hep2 cells turned to spindle-like shapes after exposed to
      shear stress, and showed the trend of the recovering to original shapes when the
      shear stress was cancelled. The cell-cell junctions were tight under the shear
      flow condition, and the permeability was reduced under the condition of 1.4
      dyn/cm shear flow. The expressions of tight junction proteins were enhanced with
      increased duration of shear flow, but reduced after removing shear flow. The
      result of Claudin-5 expression by immufluorescence assay was consistent with that
      by Western blot. The Claudin-5 mainly distributed in the cytoplasm under static
      condition, while it located at the intercellular after shear flow stimulation,
      and it appeared intercellular and cytoplasm after stopping shear flow
      stimulation. Therefore, it can be concluded that shear stress changes the
      morphology of laryngeal squamous carcinoma Hep2 cells, and upregulates the tight
      junction.

PMID- 25997276
TI  - [Effects of madder on bone biomechanical property in rats].
AB  - Bones are stained into red color with feeding madder, but we do not know whether
      the fed madder can change the bone biomechanical properties and bone mineral
      contents in animals. In this research, we established a rat model with feeding
      madder. The bone biomechanical properties were detected by universal material
      mechanics, bone mineral contents were detected by inductively coupled plasma mass
      spectrometry and spectrometer, and red color material in bone was analyzed by
      high performance liquid chromatography. The results showed that bone
      biomechanical parameters in femur diaphysis in the 10% and 15% group rats were
      significantly higher than those in the control group after feeding madder for 6
      months. The level of calcium, magnesium and zinc in femur diaphysis in 10% and
      15% group rats were higher than those in the control group after feeding madder
      for 6 months. However, it was shown that the kidney congestion and hyperemia and
      the level of blood urea nitrogen and creatinine in the 15% group rats were
      significantly different compared to those in the control group rats after feeding
      madder for 6 months. The red colored material in bone is related to alizarin
      analyzed with high-performance liquid chromatography. The conclusion could be
      drawn that feeding 10% madder in diet was not toxic to the rats fed for 6 months,
      and it could improve bone biomechanical properties and increase bone mineral
      elements.

PMID- 25997277
TI  - [Effects of 50 Hz sinusoidal electromagnetic field with different intensities on
      rat peak bone mass].
AB  - Studying effects of 50 Hz sinusoidal electromagnetic fields (SEMFs) with
      different intensities on peak bone mass (PBM) of rats may provide a theoretical
      basis for application of electromagnetic clinical field. 30 female SD rats, 6
      weeks of age, were randomly divided into three groups: the control group, 0.1 mT
      electromagnetic field group (EMFs) and 0.6 mT EMFs. The EMFs groups were treated
      for 3 h/day. After 8 weeks, we examined their bone mineral densities (BMD) ,
      measured their bone biomechanical properties, and made serum levels of
      osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRACP 5b), and
      histomorphometry. It was found that the BMD (P < 0.01), maximum mechanical load
      (P < 0.01) in the 0.1 mT group were significantly higher than those in the
      control group, and Yield strength (P < 0.05), the analyses of serum bone turnover
      markers and histomorphometric parameters were better than those in the control
      group (P < 0.05). However, the 0.6 mT group did not have significantly difference
      comparing with that in the control group. This study proved that 50 Hz 0.1 mT
      SEMFs can increased BMD, bone strength, and bone tissue microstructure.
      Therefore, 50 Hz 0.1 mT SEMFs can improve peak bone mass of rats.

PMID- 25997278
TI  - [Recombinant expression and characterization of CD2-binding domain of Macaca
      mulatta lymphocyte function-associated antigen 3 in Pichia pastoris].
AB  - Human lymphocyte function-associated antigen 3 (hLFA3) has been identified as an
      important T cell accessory molecule. Rhesus monkeys (Macaca mulatta) have been
      widely used as animal models for human immune disorders. Due to the species
      specificity of immune system, it is necessary to study M. mulatta LFA3 (mmLFA3).
      In this study, the gene encoding mmLFA3 CD2-binding domain (mmLFA3Sh) was
      amplified by polymerase chain reaction (PCR) and genetically fused to human IgG1
      Fc fragment in pPIC9K to construct the expression plasmid pPIC9K-mmLFA3Sh-Ig.
      Approximately 3-4 mg mmLFA3Sh-Ig protein was recovered from 1 L of inductive
      media, and mmLFA3Sh-Ig produced by the P. pastoris can bind to the CD2 positive
      cells, and suppress the monkey and human lymphocytes proliferation induced by Con
      A and alloantigen in a dose-dependent manner. These results suggested that
      mmLFA3Sh-Ig might be used as a novel tool for pathogenesis and experimental
      immunotherapy of Rhesus monkey immune disorders.

PMID- 25997279
TI  - [Research on regulation function of gamma-secretase inhibitor DAPT on the
      differentiation of neural precursor cell line].
AB  - This study aims to investigate the effect of gamma-Secretase Inhibitor DAPT, (N
      [N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), on the
      differentiation of neural precursor cells and the production of neurons in the
      neural precursor cell line GE6. GE6 was cultured in medium with 4 MUmol/L DAPT
      added as the experimental group and the untreated medium separately as the
      control group. After 4 days of differentiation, we carried out the following
      experiments. We used immuno-fluorescent staining to observe the ratio of Tuj1,
      GFAP and O4 positive cells. We also used qRT-PCR to detect the effect of the DAPT
      on Tuj1 and GFAP mRNA transcription in the GE6. The results of immuno-fluorescent
      staining indicated that the Tuj1 ratio of experimental group was higher compared
      to that of the control group, but the GFAP and O4 ratio of experimental group was
      lower than that of the control group. The differences were statistically
      significant (P < 0.05). The result of qRT-PCR was in accordance with
      immunofluorescent staining results. It was well concluded that DAPT could promote
      the neurogenic differentiation of neural precursor cell line rather than leading
      to gliogenic differentiation. More neurons could be obtained for transplantation
      with the addition of DAPT.

PMID- 25997280
TI  - [Study on whorl swarming growth phenomenon of Proteus mirabilis].
AB  - The present paper is aimed to explore the origins of Proteus mirabilis (PM) whorl
      swarming growth phenomenon. The whorl swarming growth phenomenon of PM was
      observed by changed bacterial culture inoculation time, humidity, vaccination
      practices, cultured flat placement, magnetic field, pH and other factors.
      Bacterial ring spiral direction of rotation is counterclockwise and the volatile
      growth process of PM was whorl swarming growth phenomenon. Spiro fluctuation
      phenomenon was of high frequency in the sealing tanks by cultured anytime
      inoculation, wherever inoculation technique applied or not, the presence or
      absence of the magnetic field, and wherever the dish position was. The
      experimental results showed that the whorl swarming growth phenomenon of PM
      requires specific pH environment, in which the facts may be relative to its
      genetic characteristics and the Earths rotation.

PMID- 25997281
TI  - [Optimization of triple plasmids transfection into HEK293 cells mediated by
      polyethylenimine].
AB  - In the present study, packaging system composed of pAAV-CMV-GFP, pAAV-RC and
      pHelper were transfected into human embryonic kidney 293 cells (HEK293 cells)
      mediated by polyethyleneimine (PEI) to explore an optimal transfection condition.
      Different total plasmid DNA dosages (1, 2, 3, 4, 5, 6 MUg) and different
      PEI/Plasmid ratios (1:1, 3:1, 5:1, 7:1) were tested with detection of green
      fluorescence protein (GFP) with ImagePro Plus6. 0 Software. Then transfection
      efficiency of the optimized transfection system was further observed for
      different time periods(12, 24, 36, 48, 60, 72 h). The results showed that total
      plasmid dosage of 4 MUg/well with PEI/plasmid ratio of 3 : 1-5 : 1 was an
      efficient transfection condition. Transfection efficiency-time curve was an S
      shaped curve. Transfection efficiency reached a plateau at 60 h after
      transfection. The optimized conditions for PEI-mediated transfection at the
      optimal time result in enhanced transfection efficiency of triple plasmid into
      HEK293 cells.

PMID- 25997282
TI  - [Study on objectively evaluating skin aging according to areas of skin texture].
AB  - Skin aging principles play important roles in skin disease diagnosis, the
      evaluation of skin cosmetic effect, forensic identification and age
      identification in sports competition, etc. This paper proposes a new method to
      evaluate the skin aging objectively and quantitatively by skin texture area.
      Firstly, the enlarged skin image was acquired. Then, the skin texture image was
      segmented by using the iterative threshold method, and the skin ridge image was
      extracted according to the watershed algorithm. Finally, the skin ridge areas of
      the skin texture were extracted. The experiment data showed that the average
      areas of skin ridges, of both men and women, had a good correlation with age (the
      correlation coefficient r of male was 0.938, and the correlation coefficient r of
      female was 0.922), and skin texture area and age regression curve showed that the
      skin texture area increased with age. Therefore, it is effective to evaluate skin
      aging objectively by the new method presented in this paper.

PMID- 25997283
TI  - [Experimental research on the prevention of rabbit postoperative abdominal cavity
      adhesion with PLGA membrane].
AB  - The aim of this paper is to explore the prevention of rabbit postoperative
      abdominal cavity adhesion with poly (lactic-co-glycotic acid) (PLGA) membrane and
      the mechanism of this prevention function. Sixty-six Japanese white rabbits were
      randomly divided into normal control group, model control group and PLGA membrane
      group. The rabbits were treated with multifactor methods to establish the
      postoperative abdominal cavity adhesion models except for those in the normal
      control group. PLGA membrane was used to cover the wounds of rabbits in the PLGA
      membrane group and nothing covered the wounds of rabbits in the model control
      group. The hematologic parameters, liver and kidney functions and fibrinogen
      contents were detected at different time. The rabbit were sacrificed 1, 2, 4, 6,
      12 weeks after the operations, respectively. The adhesions were graded blindly,
      and Masson staining and immunohistochemistry methods were used to observe the
      proliferation of collagen fiber and the expression of transforming growth factor
      beta1 (TGF-beta1) on the cecal tissues, respectively. The grade of abdominal
      cavity adhesion showed that the PLGA membrane-treated group was significant lower
      than that in the model control group, and it has no influence on liver and kidney
      function and hematologic parameters. But the fibrinogen content and the number of
      white blood cell in the PLGA membrane group were significant lower than those of
      model control group 1 week and 2 weeks after operation, respectively. The density
      of collagen fiber and optical density of TGF-beta1 in the PLGA membrane group
      were significant lower than those of model control group. The results
      demonstrated that PLGA membrane could be effective in preventing the abdominal
      adhesions in rabbits, and it was mostly involved in the reducing of fibrinogen
      exudation, and inhibited the proliferation of collagen fiber and over-expression
      of TGF-beta1.

PMID- 25997284
TI  - [Regulation of transplantation of human umbilical cord blood derived mesenchymal
      stem cells on secretion of neural biochemistry marker after traumatic brain
      injury in rats].
AB  - This research was to study the regulation of intravenous administration of human
      umbilical cord blood mesenchymal stem cells (HUCBMSCs) on secretion of neural
      specific protein in rats after traumatic brain injury (TBI), and to explore its
      mechanisms promoting the recovery of neurological function. The TBI models of
      rats were established. We then injected HUCBMSCs, labelled by Brdu (5-bromo-2
      deoxyuridine), into the TBI rats via the tail vein using modified Feeney free
      falling method. The levels of neural biochemical indicators (serum S100beta
      protein, NSE, LDH, CK) of rats were detected in shamed group, injury group and
      HUCBMSCs-transplanted group. And the morphological changes of brain tissue of
      rats in the three groups were observed by using HE staining under light
      microscope. During the whole experiment no immunosuppressant was used for the
      four groups. From the research, transplant-related death of the rats was not
      found in transplantation group. In the injury group, rises were found in contents
      of serum S100beta protein, NSE, LDH, CK in the early stage after the rats were
      injured, which were much higher than those in shamed group at correspondent time
      point (P < 0.01). In HUCBMSCs-transplanted group, although these biochemistry
      indexes were found rising for a short period in the early stage, along with the
      time, these indexes were obviously lower than in those injury group (P < 0.05).
      Under light microscopy pathological changes of rats in HUCBMSCs-transplanted
      group were much slighter than those in injury group. It was well concluded that
      in the situation of no immuno-suppressants, the intravenous-injected HUCBMSCs
      could reduce the secretion of serum S100beta protein, NSE, LDH, CK, promote the
      repair of tissue injury effectively, and promote the functional recovery of
      neurons.

PMID- 25997285
TI  - [Multidetector CT and magnetic resonance imaging features of solitary fibrous
      tumors in the pelvis and the relevant pathologic basis changes].
AB  - In order to investigate the features of multidetector CT (MDCT) and magnetic
      resonance imaging (MRI) as well as the corresponding pathogic basis of solitary
      fibrous tumor (SFT) in the pelvis, we collected the clinical data of 13 patients
      with pathologically confirmed SFT in pelvis, and retrospectively reviewed the
      MDCT and MRI appearances. Of these enrolled patients, 6 received MDCT scans, 5
      underwent MRI scans, and 2 underwent both MDCT and MRI examinations. Shown on the
      MDCT and MRI, the maximum diameters of the masses ranged from 4.0 to 25.2 cm
      (averaged 11.8 cm). Six masses were lobulated, and seven were round or oval. In
      addition, all masses were well-defined and displaced the adjacent structures to
      some degrees. On the computed tomography, all masses were of isodensity on
      unenhanced scans in general, among which five masses were demonstrated with
      hypodense areas. On the MRI T1-weighted image, all lesions were isointense, of
      which patchy hypointense areas were detected in 3 cases and radial hypointense
      areas were in 3 cases, and the other one was presented with homogenous intensity.
      On T2-weighted images, most of the lesions were mixed hyperintense, of which 3
      cases were of heterogenous hyperintesity, radial hypointense areas were detected
      in 3 patients, and the other one was homogenously intense. On enhanced computed
      tomography and MRI, large supplying vessels were found in 4 cases; 12 cases
      showed moderate to conspicuous enhancement, and the other one was presented with
      mild homogenous enhancement. Of the patients with moderate to conspicuous
      enhancement, patchy areas of non-enhancement were detected in 7 cases, radial
      areas of progressive enhancement were detected in 3 cases, and the remained 2
      cases showed homogenous enhancement. On pathology, the radial area presented as
      progressive enhancement was fibrosis. During the follow-ups after surgery, 2
      patients had local recurrence and 1 had metastasis to liver. In conclusion, the
      SFT in the pelvis are commonly presented as a large solid, well-defined and
      hypervascular mass with necrosis or cystic changes at some extents together with
      the displacement of adjacent structures. The radial area with hypointensity on T2
      weighted image and with progressive enhancement on enhanced magnetic resonance
      imaging is an important feature of SFT, which can be helpful for the diagnosis of
      this mass.

PMID- 25997286
TI  - [Evaluating the left ventricular diastolic function of diabetes mellitus patients
      using dual-gate Doppler].
AB  - To evaluate the value of left ventricular diastolic function in type 2 diabetes
      mellitus (DM) using dual-gate Doppler and relative factors, we included 50 non
      obesity and hypertension-free DM patients into the controlled group in the study
      along with 48 age-and-gender-matched healthy volunteer subjects. The peak early
      diastolic velocity (E), peak later diastolic velocity (A), deceleration time
      (DT), anterior mitral annulus diastolic peak velocity (e') , isovolumic
      relaxation time (IVRT), E/A, E/e', Tei index and T(E-e), were measured with dual
      gate Doppler. 20 subjects were randomly selected for repetitive analysis. Study
      showed statistical difference in E/A, DT, e', E/e', IVRT, Tei index and T(E-e),
      between the two groups (P < 0.05). Linear regression analysis showed positive
      correlation between T(E-e), and IVRT, course of DM patients and T(E-e), (Beta =
      0.295, P = 0.020), and HbA1c control level and T(E-e), (Beta = 0.399, P = 0.010).
      Repeated analysis showed good reproducibility for both within and between groups.
      Dual-gate Doppler has clinical value in evaluating left ventricular diastolic
      function in type 2 diabetes mellitus patients. The course of type 2 diabetes
      mellitus patients and HbA(1C) control level were both closely related with left
      ventricular diastolic function.

PMID- 25997287
TI  - [Design of a system for real-time seizure detection and closed-loop electrical
      stimulation].
AB  - In order to investigate the effect of deep brain stimulation on diseases such as
      epilepsy, we developed a closed-loop electrical stimulation system using LabVIEW
      virtual instrument environment and NI data acquisition card. The system was used
      to detect electrical signals of epileptic seizures automatically and to generate
      electrical stimuli. We designed a novel automatic detection algorithm of
      epileptic seizures by combining three features of field potentials: the
      amplitude, slope and coastline index. Experimental results of rat epileptic model
      in the hippocampal region showed that the system was able to detect epileptic
      seizures with an accuracy rate 91.3% and false rate 8.0%. Furthermore, the on
      line high frequency electrical stimuli showed a suppression effect on seizures.
      In addition, the system was adaptive and flexible with multiple work modes, such
      as automatic and manual modes. Moreover, the simple time-domain algorithm of
      seizure detection guaranteed the real-time feature of the system and provided an
      easy-to-use equipment for the experiment researches of epilepsy control by
      electrical stimulation.

PMID- 25997288
TI  - [Scoring methods for liver tissue fibrosis based on ultrasound radio frequency
      time series].
AB  - Trying to provide ultrasonic image-aid measures for quantitative diagnosis and
      dynamic monitoring of liver fibrosis, we propose two scoring methods for liver
      fibrosis tissue in vivo , based on ultrasound radio frequency (RF) time series in
      this paper. Firstly, RF echo signals of human liver were recorded in this study.
      Then one of the recorded frame RF data was demodulated to be B model image. After
      that, a region of interest (ROI) in the B model image was selected. For each
      point in the ROI, its all frame data were acquired so that RF time series were
      formed. An SMR (size measure relationship) fractal dimension and six spectral
      features were extracted from RF time series in the ROI. With relative deviation
      and Fisher's discriminant ratio, seven features were weighted and summed so that
      the liver tissues' scores were obtained, Score-rd and Score-fisher, respectively.
      Area under ROC curve (AUC) and a support vector machine (SVM) were used to
      evaluate whether these scoring methods would be useful in distinguishing normal
      and cirrhosis tissues. Experimental results are shown as follows: Score-rd's AUC
      was 0.843, while Score-fisher was 0.816, SVM classification accuracies were both
      up to 87.5%. This proved that our proposed scoring methods were effective in
      distinguishing normal and cirrhosis tissues. Score-rd and Score-fisher have
      potential for clinical applications. They can also provide quantitative
      references for liver fibrosis diagnosis.

PMID- 25997289
TI  - [Magnetic resonance image fusion based on three dimensional band limited shearlet
      transform].
AB  - More and more medical devices can capture different features of human body and
      form three dimensional (3D) images. In clinical applications, usually it is
      required to fuse multiple source images containing different and crucial
      information into one for the purpose of assisting medical treatment. However,
      traditional image fusion methods are normally designed for two dimensional (2D)
      images and will lead to loss of the third dimensional information if directly
      applied to 3D data. Therefore, a novel 3D magnetic image fusion method was
      proposed based on the combination of newly invented beyond wavelet transform,
      called 3D band limited shearlet transformand (BLST), and four groups of
      traditional fusion rules. The proposed method was then compared with the 2D and
      3D wavelet and dual-tree complex wavelet transform fusion methods through 4
      groups of human brain T2* and quantitative susceptibility mapping (QSM) images.
      The experiments indicated that the performance of the method based on 3D
      transform was generally superior to the existing methods based on 2D transform.
      Taking advantage of direction representation, shearlet transform could
      effectively improve the performance of conventional fusion method based on 3D
      transform. It is well concluded, therefore, that the proposed method is the best
      among the methods based on 2D and 3D transforms.

PMID- 25997290
TI  - [Testing system design and analysis for the execution units of anti-thrombotic
      device].
AB  - In an anti-thrombotic pressure circulatory device, relays and solenoid valves
      serve as core execution units. Thus the therapeutic efficacy and patient safety
      of the device will directly depend on their performance. A new type of testing
      system for relays and solenoid valves used in the anti-thrombotic device has been
      developed, which can test action response time and fatigue performance of relay
      and solenoid valve. PC, data acquisition card and test platform are used in this
      testing system based on human-computer interaction testing modules. The testing
      objectives are realized by using the virtual instrument technology, the high
      speed data acquisition technology and reasonable software design. The two sets of
      the system made by relay and solenoid valve are tested. The results proved the
      universality and reliability of the testing system so that these relays and
      solenoid valves could be accurately used in the antithrombotic pressure
      circulatory equipment. The newly-developed testing system has a bright future in
      the aspects of promotion and application prospect.

PMID- 25997291
TI  - [Nondestructive applanation technique to measure the elasticity moduli and creep
      properties of ocular cornea in vivo].
AB  - Due to lack of the practical technique to measure the biomechanical properties of
      the ocular cornea in vivo, clinical ophthalmologists have some difficulties in
      understanding the deformation mechanism of the cornea under the action of
      physiological intraocular pressures. Using Young's theory analysis of the corneal
      deformation during applanation tonometry, the relation between the elasticity
      moduli of the cornea and the applanated corneal area and the measured and true
      intraocular pressures can be obtained. A new applanation technique has been
      developed for measuring the biomechanical properties of the ocular cornea tissue
      in vivo, which can simultaneously acquire the data of the applanation area and
      displacement of the corneal deformation as well as the exerted applanation force
      on the cornea. Experimental results on a rabbit's eyeball demonstrated that the
      present technique could be used to measure the elasticity moduli and creep
      properties of the ocular cornea nondestructively in vivo.

PMID- 25997292
TI  - Study of characteristic point identification and preprocessing method for pulse
      wave signals.
AB  - Characteristics in pulse wave signals (PWSs) include the information of
      physiology and pathology of human cardiovascular system. Therefore,
      identification of characteristic points in PWSs plays a significant role in
      analyzing human cardiovascular system. Particularly, the characteristic points
      show personal dependent features and are easy to be affected. Acquiring a signal
      with high signal-to-noise ratio (SNR) and integrity is fundamentally important to
      precisely identify the characteristic points. Based on the mathematical
      morphology theory, we design a combined filter, which can effectively suppress
      the baseline drift and remove the high-frequency noise simultaneously, to
      preprocess the PWSs. Furthermore, the characteristic points of the preprocessed
      signal are extracted according to its position relations with the zero-crossing
      points of wavelet coefficients of the signal. In addition, the differential
      method is adopted to calibrate the position offset of characteristic points
      caused by the wavelet transform. We investigated four typical PWSs reconstructed
      by three Gaussian functions with tunable parameters. The numerical results
      suggested that the proposed method could identify the characteristic points of
      PWSs accurately.

PMID- 25997293
TI  - [Development method of healthcare information system integration based on
      business collaboration model].
AB  - Integration of heterogeneous systems is the key to hospital information
      construction due to complexity of the healthcare environment. Currently, during
      the process of healthcare information system integration, people participating in
      integration project usually communicate by free-format document, which impairs
      the efficiency and adaptability of integration. A method utilizing business
      process model and notation (BPMN) to model integration requirement and
      automatically transforming it to executable integration configuration was
      proposed in this paper. Based on the method, a tool was developed to model
      integration requirement and transform it to integration configuration. In
      addition, an integration case in radiology scenario was used to verify the
      method.

PMID- 25997294
TI  - [Acute hypotensive episodes prediction based on non-linear chaotic analysis].
AB  - In intensive care units (ICU) , the occurrence of acute hypotensive episodes
      (AHE) is the key problem for the clinical research and it is meaningful for
      clinical care if we can use appropriate computational technologies to predict the
      AHE. In this study, based on the records of patients in ICU from the MIMIC II
      clinical data, the chaos signal analysis method was applied to the time series of
      mean artery pressure, and then the patient's Lyapunov exponent curve was drawn
      ultimately. The research showed that a curve mutation appeared before AHE
      symptoms took place. This is powerful and clear basis for AHE determination. It
      is also expected that this study may offer a reference to research of AHE theory
      and clinical application.

PMID- 25997295
TI  - [Latest development of intestinal capsule endoscopy robot].
AB  - With the development of capsule endoscopy, developing active capsule endoscopy
      robot becomes a growing trend. Although stomach diagnosis with robot has been put
      into clinical test, the realization of the complete intestinal capsule endoscopy
      is still a difficulty. This paper reports the status quo of the research process
      for intestinal capsule endoscopy robot, and analyzes their advantages, defects
      and prospects for development, which provides reference for the research of
      intestinal capsule endoscopy robot.

PMID- 25997296
TI  - [Recent technical research hot spots and development progresses in medical whole
      body positron emission tomography].
AB  - Medical whole-body positron emission tomography (PET), one of the most successful
      molecular imaging technologies, has been widely used in the fields of cancer
      diagnosis, cardiovascular disease diagnosis and cranial nerve study. But, on the
      other hand, the sensitivity, spatial resolution and signal-noise-ratio of the
      commercial medical whole-body PET systems still have some shortcomings and a
      great room for improvement. The sensitivity, spatial resolution and signal-noise
      ratio of PET system are largely affected by the performances of the scintillators
      and the photo detectors. The design of a PET system is usually a trade-off in
      cost and performance. A better image quality can be achieved by optimizing and
      balancing the key components which affect the system performance the most without
      dramatically increases in cost. With the development of the scintillator, photo
      detector and high speed electronic system, the performance of medical whole-body
      PET system would be dramatically improved. In this paper, we report current
      progresses and discuss future directions of the developments of technologies in
      medical whole-body PET system.

PMID- 25997297
TI  - [Application status of rapid prototyping technology in artificial bone based on
      reverse engineering].
AB  - Artificial bone replacement has made an important contribution to safeguard human
      health and improve the quality of life. The application requirements of rapid
      prototyping technology based on reverse engineering in individualized artificial
      bone with individual differences are particularly urgent. This paper reviewed the
      current research and applications of rapid prototyping and reverse engineering in
      artificial bone. The research developments and the outlook of bone kinematics and
      dynamics simulation are also introduced.

PMID- 25997298
TI  - [Research progress on emotion recognition based on physiological signals].
AB  - Emotion recognition will be prosperious in multifarious applications, like
      distance education, healthcare, and human-computer interactions, etc. Emotions
      can be recognized from the behavior signals such as speech, facial expressions,
      gestures or the physiological signals such as electroencephalogram and
      electrocardiogram. Contrast to other methods, the physiological signals based
      emotion recognition can achieve more objective and effective results because it
      is almost impossible to be disguised. This paper introduces recent advancements
      in emotion research using physiological signals, specified to its emotion model,
      elicitation stimuli, feature extraction and classification methods. Finally the
      paper also discusses some research challenges and future developments.

PMID- 25997299
TI  - [Study on the regulatory effects of mechano growth factor on soft tissue repair].
AB  - Mechano growth factor (MGF) is an autocrine/paracrine factor and sensitive to
      mechanical stimulation. MGF can be highly expressed in various soft tissues under
      physical stimuli, biochemistry stimuli or in damaged situation. MGF may
      "compensate" the stress for tissue in the processing of tissue repair. MGF can
      effectively accelerate the repair of the soft tissue by promoting the
      proliferation, migration and differentiation of cells. This paper summarizes the
      MGF expressions in different soft tissues and their functions in soft tissue
      repair. The paper also discusses current problems and challenges in using MGF to
      repair the soft tissue.

PMID- 25997300
TI  - [Potential therapeutic effect of paracrine factors from bone marrow-derived
      mesenchyme stem cells in the treatment of severe acute pancreatitis].
AB  - Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is one ot the
      most popular therapeutic measures in severe acute pancreatitis (SAP). However,
      technical challenges and ethical concern have hindered its clinical application.
      Paracrine factor, as a new safe and easy handing therapeutic measure, can work
      comparably effective as BMSC transplantation in SAP therapy, but bio-safe risks
      could be greatly reduced. In this paper, we reviewed the therapeutic effect and
      potential mechanism of paracrine factors in the treatment of SAP. The injection
      of paracrine factors yielded from cultured cell suspension will be a new cell
      therapeutic measure for SAP.

PMID- 25997301
TI  - Anticholinergics for treatment of asthma.
AB  - Asthma management guidelines emphasize the importance of effective treatment to
      achieve and maintain control of asthma. However, despite widely available and
      effective treatments, achieving control of asthma is still an unmet need for many
      patients. Adding a second bronchodilator with a different mechanism of action for
      the treatment of uncontrolled asthma can be a suitable therapeutic approach. This
      review focuses on the role of long-acting muscarinic antagonists, particularly
      tiotropium, in the treatment of asthma. A number of studies have evaluated the
      efficacy and safety of tiotropium in asthma patients whose disease is poorly
      controlled with inhaled corticosteroids (ICSs) with or without long-acting beta2
      agonists (LABAs). The effect on several clinical and lung function variables of
      adding tiotropium to an ICS is greater than doubling the dose of the latter and
      is not inferior to the addition of a LABA (salmeterol). Studies assessing the
      role of tiotropium as add-on therapy to ICS combined with a LABA have shown
      modest but clinically significant and dose-dependent improvements in forced
      expiratory volume in 1 second, as well as a decrease in the risk of
      exacerbations. In addition, time to the next episode is longer, particularly in
      patients who experience severe exacerbations. In conclusion, tiotropium proved
      noninferior to salmeterol and superior to placebo in patients with moderate
      severe asthma who were not adequately controlled using ICSs or ICSs combined with
      a LABA. The major benefits are the increase in lung function and, in the case of
      severe asthma, the reduction in the frequency of exacerbations. In patients with
      asthma, tiotropium is usually well tolerated, and no potential safety signals
      have been observed.

PMID- 25997302
TI  - Consensus document on allergic conjunctivitis (DECA).
AB  - Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused
      mainly by an IgE-mediated mechanism. It is the most common type of ocular
      allergy. Despite being the most benign form of conjunctivitis, AC has a
      considerable effect on patient quality of life, reduces work productivity, and
      increases health care costs. No consensus has been reached on its classification,
      diagnosis, or treatment. Consequently, the literature provides little information
      on its natural history, epidemiological data are scarce, and it is often
      difficult to ascertain its true morbidity. The main objective of the Consensus
      Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis
      Alergica [DECA]), which was drafted by an expert panel from the Spanish Society
      of Allergology and Spanish Society of Ophthalmology, was to reach agreement on
      basic criteria that could prove useful for both specialists and primary care
      physicians and facilitate the diagnosis, classification, and treatment of AC.
      This document is the first of its kind to describe and analyze aspects of AC that
      could make it possible to control symptoms.

PMID- 25997303
TI  - Cutoff point for exhaled nitric oxide corresponding to 3% sputum eosinophils.
AB  - BACKGROUND: The eosinophilic asthma phenotype (sputum eosinophils 3%) indicates a
      good response to corticosteroids and T(H)2 immunomodulators. Exhaled nitric oxide
      (FeNO) is rapidly measured by portable devices, and although it is not a
      selective marker of eosinophilic inflammation, several studies have demonstrated
      a strong correlation with it. We investigated which FeNO value was the best fit
      with 3% sputum eosinophils in asthma patients. METHODS: We included 129
      consecutive, nonsmoking asthmatics who underwent skin tests, FeNO quantification
      (NIOX MINO), spirometry, and induced sputum analysis and completed the Asthma
      Control Test questionnaire. Receiver operating characteristic curves were
      constructed, and logistic regression analysis was performed. RESULTS: Symptoms
      were detected more frequently in the eosinophilic asthma group, as were higher
      airway obstruction and sensitivity to hypertonic saline. The FeNO cutoff point of
      21 ppb was the best fit with 3% sputum eosinophilia. This value behaved better
      among corticosteroid-naive patients (sensitivity, 97%; specificity, 58%; positive
      predictive value, 86%; negative predictive value, 88%) than among those receiving
      corticosteroids (sensitivity, 81%; specificity, 25%; positive predictive value,
      74%; negative predictive value, 33%). CONCLUSION: FeNO >= 21 ppb is associated
      with airway eosinophilia. In corticosteroid-naive patients, FeNO < 21 ppb enables
      us to rule out airway eosinophilia.

PMID- 25997304
TI  - Autoimmunity in patients with selective IgA deficiency.
AB  - BACKGROUND AND OBJECTIVE: Selective immunoglobulin A deficiency (SIgAD) is the
      most common primary antibody deticiency. Patients with SIgAD have a greater risk
      of concomitant autoimmune disorders than healthy individuals. The exact mechanism
      underlying the relationship between autoimmunity and SIgAD is not fully
      understood. The aim of this study was to evaluate potential associations between
      autoimmunity and specific clinical or immunological findings in patients with
      SIgAD. METHODS: The study population comprised 57 symptomatic patients (65%
      males) with confirmed SIgAD who were referred to our center. Demographic data and
      history of autoimmunity were recorded both for patients and for their relatives.
      Comprehensive clinical and laboratory examinations were performed to investigate
      autoimmune complications in all the patients. RESULTS: Autoimmune disorders were
      documented in 17 cases (29.8%; 9 males and 8 females). The most common
      manifestations were thyroiditis, vitiligo, and hemolytic anemia (3 cases each).
      Ten patients (17.5%) had a family history of autoimmunity. Significant
      associations were detected between autoimmunity and increased duration of follow
      up (P = .003), serum level of IgM (P = .01), regulatory T-cell count (P = .03),
      and class-switched memory B-cell count (P = .01). Four cases of autoimmune SIgAD
      (23.5%) progressed to common variable immunodeficiency during the follow-up
      period (P = .006). CONCLUSIONS: Autoimmune disorders, autoimmune cytopenia, and
      Ig subclass deficiency can lead to severe clinical manifestations in patients
      with SIgAD. Therefore, immunologists and pediatricians should be aware of these
      conditions.

PMID- 25997305
TI  - Relationship between serum total IgE and disease severity in patients with
      allergic asthma in Spain.
AB  - OBJECTIVES: To evaluate the association between serum total IgE levels and
      disease severity in adult patients with persistent allergic asthma and to explore
      the main predictors of IgE levels. METHODS: We performed a multicenter,
      retrospective, observational study including adult patients diagnosed >= 1 year
      previously with persistent allergic asthma who were positive to >= 1 allergen.
      Patients also had serum total IgE and spirometry results available from the
      previous 12 months. Inclusion was stratified by asthma severity according to the
      GEMA 2009 criteria. RESULTS: We included 383 patients with allergic asthma (129
      mild, 82 moderate, and 172 severe). Mean (SD) age was 38 (15), 46 (16), and 45
      (15) years, respectively (P < 0.001). Serum total IgE levels varied markedly
      (coefficient of variation, 147%). No association was observed with forced
      expiratory volume in 1 second (FEV1) or asthma severity: mean (SD)/median (IQR)
      of 403 (616)/214 (108-409), 361 (516)/204 (126-361), and 473 (676)/211 (98-545)
      IU/mL in the mild, moderate, and severe subgroups, respectively (P = .951). The
      severe subgroup had a higher percentage of patients with > 400 IU/mL (36% vs
      26.4% [mild] and 18.3% [moderate], P = .010). In a multivariate multiple
      regression model, the independent predictors of higher IgE were younger age (P =
      .004), sensitization to >= 2 allergens (P = .009), male gender (P = .025), and
      family history of asthma (P = .122). CONCLUSION: Serum total IgE levels in adult
      patients with persistent allergic asthma were high (two-thirds with levels > 150
      IU/mL) and extremely variable. We did not find a significant association between
      serum total IgE levels and asthma severity or airflow limitation, except for a
      higher percentage of patients with IgE > 400 IU/mL in the severe subgroup.

PMID- 25997306
TI  - Azithromycin is more allergenic than clarithromycin in children with suspected
      hypersensitivity reaction to macrolides.
AB  - BACKGROUND: Macrolides are considered safe antibiotics with reduced allergenic
      activity. However, studies on the safety of macrolides are scarce, particularly
      in children. OBJECTIVE: The aim of this study was to assess the frequency of
      hypersensitivity reactions to clarithromycin and azithromycin in a group of
      children referred to our allergy unit for suspected macrolide allergy. METHODS:
      We retrospectively reviewed the charts of 90 children aged 1-17 years with
      symptoms suggestive of hypersensitivity reaction to clarithromycin or
      azithromycin between December 31, 2008 and December 31, 2013. The allergy workup
      included skin tests (ie, skin prick tests and/or intradermal tests),
      determination of serum specific IgE (sIgE) to clarithromycin and azithromycin,
      and, if necessary to reach a diagnosis, oral provocation tests. RESULTS: Seventy
      seven children completed the allergy workup. A reaction to clarithromycin was
      recorded in 58 children (75.3%): 21 (36.2%) had a history of immediate reactions,
      and 37 (63.8%) had a history of nonimmediate reactions. A reaction to
      azithromycin was recorded in 19 children (24.6%): 6 (31.5%) had a history of
      immediate reaction, and 13 (68.42%) had a history of nonimmediate reaction.
      Positive results in skin tests and oral provocation tests with the suspect drug
      confirmed the diagnosis in 15.5% of reactions to clarithromycin (9 of 58) and in
      47.3% of reactions to azithromycin (9 of 19) (P = .004). CONCLUSION: A complete
      allergy workup enabled us to confirm a diagnosis of clarithromycin and
      azithromycin allergy in 15.5% and 47.3% of cases, respectively. Azithromycin was
      more allergenic than clarithromycin in children.

PMID- 25997307
TI  - Aspirin desensitization achieved after omalizumab treatment in a patient with
      aspirin-exacerbated urticaria and respiratory disease.

PMID- 25997308
TI  - Herpes-like eruption due to fluconazole.

PMID- 25997309
TI  - Rubinstein-Taybi syndrome associated with humoral immunodeficiency.

PMID- 25997310
TI  - Relief of photoallergy: atorvastatin replacing simvastatin.

PMID- 25997311
TI  - Allergic reaction to undeclared lupin in a chocolate.

PMID- 25997312
TI  - Anaphylaxis in a child after ingestion of persimmon.

PMID- 25997313
TI  - Occupational asthma to dried tobacco leaves: a very delayed diagnosis.

PMID- 25997314
TI  - Not all facial swellings are angioedemas!

PMID- 25997315
TI  - First case report of acute generalized exanthematous pustulosis due to labetalol.

PMID- 25997316
TI  - Prevalence of sensitization to pollen from trees planted in Barcelona City.

PMID- 25997317
TI  - Chlorhexidine: a retrospective observational study of a potentially life
      threatening molecule.

PMID- 25997318
TI  - Fixed drug eruption due to atorvastatin.

PMID- 25997319
TI  - Aspirin desensitization in a patient with NSAID-induced delayed angioedema.

PMID- 25997320
TI  - Desensitization to lenograstim after a life- threatening reaction to filgrastim.

PMID- 25997321
TI  - The new latex allergen Hev b 15: IgE-binding properties of a recombinant serine
      protease inhibitor.

PMID- 25997322
TI  - [The establishment of high-throughput neutralization titer evaluation model for
      hepatitis E virus (HEV)].
AB  - The lack of effective in vitro infection model for hepatitis E virus (HEV) has
      greatly hindered the quantitative analysis of neutralizing titers of anti-HEV
      antibodies and human sera, thus impeding further studies of HEV-stimulated
      antibody responses and the immunological mechanisms. In order to improve this
      situation, the infection of HepG2 cells that are inefficient for HEV replication
      was continuously monitored until the viral load reached the limit of detection on
      day 13, the results of which confirmed the feasibility of using this cell line to
      establish the infection model. Then, neutralization assays of five anti-HEV
      murine monoclonal antibodies and serum samples collected from four HEV vaccine
      recipients (collected before and after vaccination) were performed by 96 multi
      channel parallel infections, nucleic acid extraction, and qPCR. The results
      showed that the cell model can be applied for quantitative evaluation of the
      neutralizing capacity of different antibodies and antiserum samples from HEV
      vaccine recipients. In this study, we have successfully established a high
      throughput in vitro HEV replication model, which will prove to be useful for the
      evaluation of HEV vaccines and studies of HEV epitopes.

PMID- 25997323
TI  - [Immunogenicity and heterologous protection in mice with a recombinant adenoviral
      based vaccine carrying a hepatitis C virus truncated NS3 and core fusion
      protein].
AB  - To develop a safe and broad-spectrum effective hepatitis C virus (HCV) T cell
      vaccine,we constructed the recombinant adenovirus-based vaccine that carried the
      hepatitis C virus truncated NS3 and core fusion proteins. The expression of the
      fusion antigen was confirmed by in vitro immunofluorescence and western blotting
      assays. Our results indicated that this vaccine not only stimulated antigen
      specific antibody responses,but also activated strong NS3-specific T cell immune
      responses. NS3-specific IFN-gamma+ and TNF-alpha+ CD4+ T cell subsets were also
      detected by a intracellular cytokine secretion assay. In a surrogate challenge
      assay based on a recombinant heterologous HCV (JFH1,2a) vaccinia virus,the
      recombinant adenovirus-based vaccine was capable of eliciting effective levels of
      cross-protection. These findings have im- portant implications for the study of
      HCV immune protection and the future development of a novel vaccine.

PMID- 25997324
TI  - [The drug resistance mutation detection and relevant factors analysis of HBV P
      region in chronic hepatitis B patients in Weifang City, Shandong Province].
AB  - In order to investigate the mutation of HBV polymerase gene reverse transcription
      conserved region (P region) in chronic hepatitis B (CHB) patients, 212 CHB
      patients who took antiretroviral treatment with nucleotide analogues were chosen.
      The drug resistance mutations of HBV P region and HBV genotype were detected by
      Pyrosequencing. Sequence analysis showed that the drug resistance sites of HBV P
      region located at sites 173; 180; 181; 184; 204; 236 and 250. The main site of
      HBV P region drug resistance was 204 and 180, accounting for 35.8% and 23.5%,
      respectively. There were significant differences in the mutation rate of site 180
      among different age groups. There were also significant differences in the
      mutation rate of site 204 among younger than 30 age group, 41 to 50 age group and
      51 to 60 age group. (P < 0.05, P < 0.01). The mutation rate of site 180 combined
      with site 204 was 66.6%. The mutation rate of site 181 combined with site 236 was
      23.3%. The age of C genotype infected patients was significantly older than B
      genotype infected patients (P < 0.01). M204V/I mutation mostly existed in the
      form of joint L180M mutation, the mutation rate was age-related. The detection of
      HBV genotypes and drug resistance sites of HBV P region have important clinical
      implications for the treatment and prognosis of patients with CHB.

PMID- 25997325
TI  - [Preparation and functional analysis of the monoclonal antibodies against severe
      fever with thrombocytopenia syndrome bunyavirus structural proteins].
AB  - To prepare monoclonal antibodies (mAbs) against structural proteins of severe
      fever with thrombocytopenia syndrome bunyavirus (SFTSV), BALB/c mice were
      immunized using purified inactivated SFTSV virions as the antigens. Subsequently,
      hybridoma cell lines that secreted monoclonal antibodies against nucleoprotein
      (NP) and glycoproteins (GP) were obtained using a hybridoma technique. The
      antigen specificities of prepared mAbs were examined by indirect
      immunofluorescence and immunoprecipitation assays. Functional analyses were then
      performed,including the detection of IFA antibody titers,the levels of
      neutralizing activity and antibody affinities. After cell fusion and cloning,13
      hybridoma cell lines secreted mAbs specifically against SFTSV-GP and 7 hybridoma
      cell lines secreted mAbs specifically against SFTSV-NP. Immunofluorescence and
      immunoprecipitation assays showed that the mAbs had high levels of antigen
      specificity. Among the 13 anti-SFTSV-GP mAbs,6 recognized Gn,whereas the others
      reacted with Gc. IFA titers of most anti-SFTSV-GP mAbs were between 1,280 and
      20,480, and four anti-SFTSV-Gn mAbs showed neutralizing activity. Seven of the
      obtained anti-SFTSV-NP mAbs reacted specifically with NP,of which the IFA titers
      ranged from 5,120 to 20,480 with no observed neutralizing activity. Furthermore,
      two anti-SFTSV-GP mAbs, 1C8 and 1G8, showed high levels of affinity via a non
      competitive ELISA. Our study lays the foundation for the development of further
      diagnostic assays and basic research into SFTSV.

PMID- 25997326
TI  - [Development of human antibodies against the Gn protein of severe fever with
      thrombocytopenia syndrome virus].
AB  - To obtain human antibodies against the Gn protein of Severe fever with
      thrombocytopenia syndrome virus (SFTSV) with phage display technology, this study
      aimed to screen anti-Gn protein antibodies from an anti-SFTSV Fab human phage
      display library. Antibody genes were identified by sequence analysis and the
      specificity of antibodies was confirmed by ELISA. The Fab antibody genes were
      cloned into the HL51-14 vector and expressed in a mammalian cell expression
      system. IgG antibodies were then purified by protein A affinity
      chromatography,and the results were further confirmed by ELISA,IFA,western
      blotting assays and micro-neutralization tests. The results showed that, after
      three rounds of panning, there were 390 human Fab antibodies against SFTSV
      particles, of which 364 were specific for nucleoprotein. Coated with the Gn
      protein, eight different Fab antibodies specific for Gn protein were obtained
      after the determination of the subtype and subclass of antibodies by gene
      sequencing; five of these antibodies were from the Lambda library and three were
      from the Kappa library. The eight IgG antibodies could specifically bind to Gn
      protein according to the ELISA, IFA and Western blotting assays. The micro
      neutralization test showed that these eight antibodies had no neutralizing
      activity,but they could still provide a reference for research in human
      monoclonal antibodies against SFTSV.

PMID- 25997327
TI  - [Virological characteristics of influenza A (H3N2) virus in mainland China during
      2013-2014].
AB  - To analyze the antigenic and genetic characteristics of the influenza A (H3N2)
      virus in mainland China during the surveillance year of 2013-2014, the antigenic
      characteristics of H3N2 virus were analyzed using reference ferret anti-sera. The
      nucleotide sequences of the viruses were determined by Sanger dideoxy sequencing,
      phylogenetic trees were constructed with the neighbor-joining method, and the
      genetic characteristics of the viruses were determined in comparison to current
      vaccine strains. The results showed that most of the H3N2 viruses were
      antigenically closely related to the A/Victoria/361/2011 vaccine strain cell
      propagated prototype virus (99.6%). Using the A/Texas/50/2012 egg isolate as the
      reference antigen, 15.1% of the viruses were found to be closely antigenically
      related to it, while 11.9% of strains were closely antigenically related to the
      egg-propagated epidemic strain, A/Shanghai-Changning/1507/2012. Phylogenetic
      analysis of HA genes indicated that the A(H3N2) viruses in this surveillance year
      were in the same clade, but no drug resistant mutation was identified in the NA
      genes. During the 2013-2014 influenza surveillance year, no significant genetic
      change was detected in either the HA or NA genes of the A(H3N2) viruses, while
      significant mutations were found in egg isolates resulting from their adaptation
      during propagation in eggs. The antigenic and genetic changes should be
      investigated in a timely manner to enable the selection of an appropriate vaccine
      strain in China.

PMID- 25997328
TI  - [Genetic analysis of Echovirus 11 isolated from patients with viral encephalitis
      in Longyan, China].
AB  - This study aimed to analyse the genetically characterize isolates of Echovirus 11
      from Longyan City,Fujian Province,and to reveal their genetic relationships with
      other isolates from China and abroad. Cerebrospinal fluid specimens from patients
      diagnosed with viral encephalitis or central nervous system (CNS) infections were
      collected from Longyan First Hospital between January and December 2011. Seven
      Echo11 strains were isolated and identified using the RIMV serum panel. The
      entire VP1 coding regions of four strains were sequenced and typed as Echo11 by
      an online blast program and,subsequently, phylogenet- ic analyses of the VP1
      sequences of these stains and others published on GenBank were conducted. There
      were 600 nucleotides (nt) in each complete VP1 coding region that encoded 200
      amino acids (aa). Among those four Echo11 strains, the sequence identities of nt
      and aa were 100% and 99%-100% respectively. And phylogenetic analyses indicate
      belong to subtype DS, the homology compared with DS strain (GU393713) were 93%
      (nt) and 99% (aa). The sequence identities for the nt and aa were 75%-76% and
      90%, respectively, between the current isolates from Longyan and the Gregory
      prototype strain found in 1953. The sequence identity of nt and aa between the
      Longyan virus strains and the domestic Shandong strains isolated in 2010 were
      lower, at 74% and 88%-89%, respectively. However,the highest level of ho- mology
      was found when the Longyan strains were compared with the Netherlands strain
      (GU393773) found in 2007 (nt and aa identity: 94%-95% and 98%-99%, respectively).
      The relatively low levels of similarity between domestic isolates suggest that
      different transmission routes exist for Echo11 in mainland China.

PMID- 25997329
TI  - [Discovery of human bocavirus 4 in children with acute gastroenteritis in
      Lanzhou, China].
AB  - We studied the epidemiological characteristics of human bocavirus 4 (HBoV4) in
      children with a- cute gastroenteritis in Lanzhou (China). A total of 331 stool
      specimens were collected from children aged < 5 years with acute diarrhea at the
      First Hospital of Lanzhou University between July 2012 and June 2013. Specimens
      of HBoV were identified by nested polymerase chain reaction assays. Compared with
      related sequences in GenBank, the HBoV-positive strain isolated in the present
      study was,quite surprisingly, a rare genotype named HBoV4. This strain was a
      typical HBoV4,with high levels of nucleotide and amino acid homology to the
      Thailand strain, JQ267789 (98.9% and 98.7%, respectively), and the USA strain,
      GQ506568 (97.6% and 97.4%, respectively). This is the first report of HBoV4 as
      the causative agent for acute gastroenteritis in pediatric patients in China.
      This strain is one of two genotypes of HBoV that are currently circulating.

PMID- 25997330
TI  - [Prokaryotic expression and identification of human astrovirus nonstructural
      proteins, nsP1a and nsP1a/4].
AB  - Human astrovirus (HastV) is recognized as one of the leading causes of acute
      viral diarrhea in infants. The HastV non-structural protein, nsPla, and C
      terminal protein, nsPla/4, contain various conserved functional domains,and may
      play an important role in virus replication, transcription and the virus-host
      interactions of HastV. This study used an E. coli system to investigate the
      expression of nsPla and nsPla/4 proteins. Firstly,the nsPla and nsPla/4 genes of
      HAstV-1 were cloned into the prokaryotic expression vector,PGEX-4T-1, to build
      the PGEX-4T-1a and PGEX-4T-la/4 fusion protein plasmids. Then, the recombinant
      plasmids were transformed into Escherichia coli BL21 (DE3) and induced with
      isopropyl-beta-D-thiogalactopyranoside (IPTG). The optimal expression conditions
      of the two fusion proteins were identified and then analyzed by polyacrylamide
      gel electrophoresis (SDS-PAGE) and western blotting, respectively. The results
      showed that the pGEX-4T-la fusion protein was maximally expressed at 30  degrees
      C after 12 hours of induction with 1.0 mM IPTG. The pGEX-4T-la/4 fusion protein
      was maximally expressed at 20  degrees C after 8 hours of induction with 0.5 mM
      IPTG. Western blot analysis showed that the two fusion proteins specificity
      reacted with the anti-nsPla and anti-GST monoclonal antibodies, respectively.
      This study successfully obtained the HAstV non-structural protein, nsP1a, and its
      C-terminal protein nsP1a/4 protein using an E. coli system. This novel study lays
      the foundation for future research into the pathogenic mechanisms of human
      astrovirus and the functions of its non-structural protein.

PMID- 25997331
TI  - [Isolation and identification of the Akabane virus from mosquitoes in Yunnan
      Province, China].
AB  - To evaluate the prevalence of mosquito-borne viruses in Manshi and Ruili (Yunnan
      Province, China), we collected 2 149 mosquitoes (17 species) in August 2010.
      Virus isolation was undertaken by the cul- ture of baby hamster kidney cells (BHK
      21 cells). Two virus-like isolates were obtained: DHL10M117 was isolated from
      collected in Mangshi; DHL10M110 was obtained from Anopheles vagus collected in
      Rui- li. Both isolates caused cytopathic effects,illness and death in suckling
      mice inoculated with these isolates via the intracerebral route. Two positive
      amplicons, 702-bp from the S segment and 456-bp from the M segment,were obtained
      using reverse transcription-polymerase chain reaction using primers specific for
      the Akabane virus (AKV). Phylogenetic analysis suggested that these two virus
      stains had a distant relation- ship with AKVs from Kenya and Australia,but were
      genetically close to those from Japan,South Korea, and Taiwan. However,they were
      separate from other Asian strains and grouped into a small branch. The highest
      nucleotide and amino-acid sequence identity of the S segment was found with the
      CY-77 strain from Taiwan (96.6% and 99.6% for DHL10M117 and 96.7% and 100% for
      DHL10M110,respectively). Com- parison of the M segment showed they shared the
      highest amino acid identity with CY-77 (99.6% and 100%, respectively), whereas
      the highest nucleotide identity was found with the Iriki strain from Japan (99.6%
      and 100%, respectively). Compared with the MP496 strain from Kenya,they displayed
      lower lev- els of sequence homology, at 69.7% and 70.0% for nucleotide sequences
      of the two loci,and 91. 0% for a- mino acids. Our results identified that
      DHL10M117 and DHL10M110 were strains of AKV,and provided molecular biological
      evidence for the existence of AKV in Yunnan Province. These AKV strains that are
      circulating in Yunnan Province share a close genetic relationship with strains
      from the rest of Asia. Culex tritaeniorhynchus and Anopheles vagus may serve as
      transmission vectors.

PMID- 25997332
TI  - [Molecular identification and sequence analysis of broad bean wilt virus 2
      isolates from atractylodes macrocephala Koidz].
AB  - To identity the pathogen that causes the mosaic and yellowing symptoms on
      Atractylodes macrocephala Koidz in Jiangxian, Shanxi province, biological
      inoculation, sequence-independent amplification (SIA),RT-PCR and other
      identification methods were used. The results showed that the chlorotic and
      necrosis symptoms occurred in the indicator plant Chenopodium quinoa after it was
      infected with the pathogen,and the same symptoms appeared after the reinoculation
      of healthy Atractylodes macrocephala Koidz; this reflected that the disease was
      likely to be caused by a virus. The results of SIA and sequencing showed that
      Broad bean wilt virus 2 (BBWV2) was present in severely mosaic Atractylodes
      macrocephala Koidz leaves. To further characterize the BBWV2 isolate from
      Atractylodes macrocephala (BBWV2-Am), the polyprotein partial gene encoded by
      BBWV2-Am RNA2 was cloned and sequenced. Sequence alignments showed that the
      nucleotide sequence identity of BBWV2-Am SCP and LCP genes ranged from 79.3% to
      87.2% and from 80.1% to 89.2% compared to other BBWV2 strains,respectively; the
      deduced amino acid sequence similarities of the two gene products ranged from
      91.2% to 95.7% and from 89.44 to 95.5%, respectively,compared to those of other
      BBWV2 strains. Phylogenetic comparisons showed that BBWV2-Am was most likely to
      be related to BBWV2-Rg,but formed an independent branch. This is the first report
      of BBWV2 in Atractylodes macrocephala Koidz.

PMID- 25997333
TI  - [Construction and identification of a recombinant PRRSV expressing ORF2 of
      porcine circovirus type 2].
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine
      circovirus type 2 (PCV2) are very two important pathogens that have coursed huge
      economic losses in swine production in worldwide. In this study,a vector pCMV-TJM
      containing the full-length cDNA clone of PRRSV attenuated strain TJM-F92 was
      firstly constructed by PCR method. Then a gene sequence containing Afl II/Mlu I e
      restriction enzyme sites and a transcription regulatory sequence for ORF6 (TRS6)
      was inserted be- tween ORF7 and 3'UTR, yielding a expression vector pCMV-TJM-TRS.
      Subsequently, a plasmid pCMV-TJM-Cap was constructed by cloning of PCV2 ORF2 gene
      into the unique sites Afl II /Mlu I of pCMV- TJM-TRS plasmid DNA. Then three
      recombinant PRRSV, rTJM, rTJM/TRS and rTJM/Cap, were rescued by transfection of
      pCMV-TJM, pCMV-TJM-TRS and pCMV-TJM-Cap into Marc-145 cells, respectively,and
      confirmed by the genome sequence, restriction enzyme digestion, Western Blot and
      IFA. They all had the molecular markers which was different from the parent
      virus. The growth characteristics of the rescued viruses were similar to that of
      parent virus. rTJM/Cap could also express efficiently PCV2 Cap protein in Marc
      145 cells. At passage 8, it still had PCV2 ORF2 gene which examined by RT-PCR. It
      indicated that the full-length cDNA clone of PRRSV attenuated strain TJM-F92 and
      recombinant PRRSV rTJM/Cap expressing PCV2 Cap protein were successfully
      constructed. It made an important foundation for studying on the pathogenic
      mechanisms of PRRSV and PRRSV-PCV2 vaccine in the future.

PMID- 25997334
TI  - [Progress in establishment and application of feline calicivirus reverse genetics
      operating system].
AB  - Feline calicivirus (FCV) is an important and highly prevalent pathogen of cats
      that causes feline respiratory disease. The reverse genetic systems for FCV have
      been established in national and international laboratories since 1995. This
      technique has been used widely in FCV basic research and good progress has
      consequently been made to determine the relationship between viral genome
      structures and the function of their proteins, the expression of foreign
      proteins, virus-host interactions, and viral pathogenic mechanisms. In this
      article,we review the state of progress with regards to the establishment and
      application of the FCV reverse genetic operating system,which will provide a
      useful reference tool for future related research.

PMID- 25997335
TI  - [Research progress in a novel H17N10 subtype of bat influenza A virus].
AB  - A novel H17N10 subtype of the influenza A viruses was found in bats in 2012.
      Protein sequence and structural analyses revealed that the HA17 and NA10 proteins
      of this strain are different from corresponding ones in known influenza A subtype
      viruses. Both HA17 and NA10 proteins cannot bind to sialic acid,which indicates
      that they may have novel functions. This article briefly describes the state of
      current research into the H17N10 subtype of bat influenza A virus.

PMID- 25997336
TI  - [Research into the antibody detection technology of mink plasmacytosis and its
      current applications].
AB  - Mink plasmacytosis, caused by Aleutian Mink Disease Virus (AMDV), poses a threat
      to the development of the animal fur industry. Neutralizing antibodies against
      AMDV may result in a persistent infection rather than providing protection for
      minks. To date,no specific methods to prevent or cure this disease have been
      developed. In order to eliminate mink plasmacytosis, antibody detection
      technology has been used globally as a dominant approach to screen for AMDV
      positive minks. This paper introduces the classical technology,
      counterimmunoelectrophoresis and emerging technology in terms of AMDV antibody
      detection,and provides a glimpse into the future development of these
      technologies.

PMID- 25997337
TI  - [Progress in studies of viperin, an important cellular antiviral factor].
AB  - Viperin is an endoplasmic reticulum (ER)-associated protein that has been
      identified as an innate antiviral protein. Viperin expression can be largely
      upregulated by viruses, interferons, and oligonucleotides such as poly I:C and
      lipopolysaccharides. Viperin inhibits viral replication by interactiing with host
      cell proteins and several viral proteins, and disrupting the cell membrane
      system. It shows a broad-spectrum of antiviral activity. Some viruses have
      developed activities that counteract the action of viperin during a long- term
      period of evolution with hosts by impairing viperin expression. In addition to
      its antiviral effects, viperin has several other biological functions. This
      article review the basic characteristics of viperin and the state of current
      research into its antiviral effects, demonstrating the rapid progress that has
      been made in this field.

PMID- 25997338
TI  - [Research on hepatitis C virus entry inhibitor].
AB  - Hepatitis c virus (HCV) infection has become one of the global public health
      problem,while there is no vaccine to prevent HCV infection, the so-called
      "cocktail" therapy that use a combination of drugs targeting multiple steps in
      the HCV infection cycle could achieve better curative effect. the process of HCV
      entering into host cell is the important step of drug intervention, in which HCV
      envelope protein El and E2, Host cell factors including Heparan sulfate(HS),
      CD81, scavenger receptor class B type I (SR-BI), Occludin (OCLD), Claudin (CLDN),
      low densitity lipoprotein receptor (LDLR), dendritic cell-specific ICAM-3
      grabbing nonintegrin (DC-SIGN), Liver/lymph node specific ICAM-3-grabbing
      integrin(L-SIGN), trans- ferrin receptor 1 (TfR1) and so on play a important
      role. The virus and the host factors can be used as targets of hcv entry
      inhibitors many studies have shown that as novel and promising compounds, HCV
      entry inhibitors combinating with other drugs can be more effective in the
      treatment of HCV, this paper have re- viewed targets and inhibitors of HCV
      enterring into host cell since 1990s.

PMID- 25997340
TI  - Microtubules, MAPs, and motor patterns.
AB  - Cells have an amazing ability to self-organize and rearrange their interiors.
      Such morphology changes are essential to cell development, division, and
      motility. The core of a cell's internal organization lies with the cytoskeleton
      made of both microtubule and actin filaments with their associated proteins and
      ATP-utilizing enzymes. Despite years of in vitro reconstitution experiments, we
      still do not fully understand how the cytoskeleton can self-organize. In an
      attempt to create a simple system of self-organization, we have used a simple
      filament-gliding assay to examine how kinesin-1-driven motion of microtubules can
      generate cell-like organization in the presence of excess filaments and
      antiparallel cross-linkers. 

PMID- 25997341
TI  - Self-organization of motors and microtubules in lipid-monolayered droplets.
AB  - In living cells, the architecture of the microtubule cytoskeleton is intimately
      linked to its function. The principles determining how microtubules arrange in
      space are, however, still not fully understood. Biochemical activities
      controlling microtubule nucleation and dynamics as well as mechanochemical
      activities exerted by molecular motors and the dynamic microtubules themselves
      are known to be critical for the correct spatial organization of the microtubule
      cytoskeleton. In vitro reconstitution approaches have revealed the morphogenetic
      properties of these activities in minimal systems. In most cases, such in vitro
      experiments were performed in experimental chambers of spatial dimensions that
      exceeded typical cell sizes by orders of magnitude. Here, we describe a method
      for the fluorescence microscopic study of the effects of spatial confinement on
      the self-organization of purified motors and microtubules that are encapsulated
      in micrometer-sized lipid-monolayered droplets emulsified in oil. In the future,
      this experimental setup can be extended in several ways. Additional proteins can
      be added, either to the lumen or to the boundary of the microcontainers, and the
      droplets can be transformed into liposomes. Such more complex in vitro
      reconstitutions would be another step closer to mimicking intracellular
      cytoskeleton organization. 

PMID- 25997339
TI  - In vitro systems for the study of microtubule-based cell polarity in fission
      yeast.
AB  - Establishment of cell polarity is essential for processes such as growth and
      division. In fission yeast, as well as other species, polarity factors travel at
      the ends of microtubules to cortical sites where they associate with the membrane
      and subsequently maintain a polarized activity pattern despite their ability to
      diffuse in the membrane. In this chapter we present methods to establish an in
      vitro system that captures the essential features of this process. This bottom-up
      approach allows us to identify the minimal molecular requirements for microtubule
      based cell polarity. We employ microfabrication techniques combined with surface
      functionalization to create rigid chambers with affinity for proteins, as well as
      microfluidic techniques to create and shape emulsion droplets with functionalized
      lipid boundaries. Preliminary results are shown demonstrating that a properly
      organized microtubule cytoskeleton can be confined to these confined spaces, and
      proteins traveling at the ends of growing microtubules can be delivered to their
      boundaries. 

PMID- 25997342
TI  - Reconstitution of microtubule-based motility using cell extracts.
AB  - Long-range intracellular transport of organelles driven by kinesin and dynein
      motor proteins depends on additional cellular factors including adaptors and
      scaffolding proteins. While single-molecule studies of the motility of purified
      motor proteins have been a powerful approach, these assays are not fully
      representative of the complex interactions that occur in a cellular environment.
      To gain insights into the functioning of adaptor proteins that work in concert
      with motors proteins, motility assays in cell extracts have been developed. These
      assays are an attractive means to begin to dissect the roles of additional
      factors in motor-driven transport. Further, this system can be easily manipulated
      to study this process in different physiological environments. Here we describe
      in vitro reconstitution of motor-driven motility along microtubules in cell
      extracts, followed by considerations for data analysis and how these assays can
      be powerful in informing our understanding of basic cellular processes. 

PMID- 25997343
TI  - Building cells for quantitative, live-cell analyses of collective motor protein
      functions.
AB  - Examining the collective mechanical behaviors of interacting cytoskeletal motors
      has become increasingly important to dissecting the complex and multifaceted
      mechanisms that regulate the transport and trafficking of materials in cells.
      Although studying these processes in living cells has been challenging, the
      development of new Synthetic Biology techniques has opened unique opportunities
      to both manipulate and probe how these motors function in groups as they navigate
      the native cytoskeleton. Here, we describe an approach to engineer mammalian
      cells for a new class of inducible cargo motility assays that utilize drug
      dependent protein dimerization switches to regulate motor-cargo coupling and
      transport. Our adaptations provide genetic-level control over the densities of
      motor proteins coupled to, as well as the sizes of endogenous vesicular cargos in
      these assays. By allowing the examination of transport responses to changes in
      motor density and cargo size-dependent viscous drag force, such control can
      enable quantitative comparisons of mechanistic distinctions between the
      collective behaviors of different types of processive cytoskeletal motors. 

PMID- 25997344
TI  - Reconstituting cytoskeletal contraction events with biomimetic actin-myosin
      active gels.
AB  - The actin-myosin cytoskeleton allows cells to move, change shape, and exert
      forces. These fascinating functions involve active contraction of cross-linked
      networks of actin filaments by myosin II motor proteins. Unlike muscle cells,
      where actin and myosin form ordered bundles that contract homogeneously,
      nonmuscle cells have a variety of more disordered types of actin-myosin
      meshworks. Active gels reconstituted from purified actin and myosin proteins
      offer a useful in vitro model system to systematically and quantitatively
      investigate the mechanisms of contraction and the role of physical parameters
      like motor activity and network connectivity. In order to quantify the effect of
      these physical parameters on contraction, time-lapse microscopy combined with
      quantitative image analysis is required. Here we describe an assay that we
      developed specifically to record contraction events of entire biomimetic active
      gels in contraction chambers, which enables one to systematically quantify the
      dependence of contraction time and length scales on experimental parameters such
      as protein concentrations, adenosine triphosphate concentration, ionic strength,
      and surface adhesion. 

PMID- 25997345
TI  - Building an artificial actin cortex on microscopic pillar arrays.
AB  - Eukaryotic cells obtain their morphology and mechanical strength from the
      cytoskeleton and in particular from the cross-linked actin network that branches
      throughout the whole cell. This actin cortex lies like a quasi-two-dimensional
      (2D) biopolymer network just below the cell membrane, to which it is attached. In
      the quest for building an artificial cell, one needs to make a biomimetic model
      of the actin cortex and combine this in a bottom-up approach with other
      "synthetic" components. Here, we describe a reconstitution method for such an
      artificial actin cortex, which is freely suspended on top of a regular array of
      pillars. By this immobilization method, the actin network is only attached to a
      surface at discrete points and can fluctuate freely in between. By discussing the
      method to make the micropillars and the way to reconstitute a quasi-2D actin
      network on top, we show how one can study an isolated, reconstituted part of a
      cell. This allows the study of fundamental interaction mechanisms of actin
      networks, providing handles to design a functional actin cortex in an artificial
      cell. 

PMID- 25997346
TI  - Triggering actin polymerization in Xenopus egg extracts from phosphoinositide
      containing lipid bilayers.
AB  - Xenopus egg extracts are a powerful tool to reconstitute complex cell biological
      processes using a cell-free strategy. When used in conjunction with liposomes and
      supported lipid bilayers, they can recapitulate the biochemical activities
      occurring at the cytosol/plasma membrane interface of the cell that underlie
      remodeling of the actin cytoskeleton. We use these in vitro systems to elucidate
      how membranes and proteins collaborate to make the appropriate actin structure at
      a given time and place. We have recently broadened the types of membrane
      substrate used, and also optimized protocols for preparation of Xenopus egg
      extracts for actin assembly assays from membranes. Tuning the lipid composition
      and curvature appropriately demands an appreciation of the native phospholipid
      and curvature environments that can form transiently in cells. Supported lipid
      bilayers on glass coverslips that contain phosphatidylserine and
      phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) make actin bundles termed
      filopodia-like structures that contain fascin and have vasodilator-stimulated
      phosphoprotein (VASP) at their growing tips, indicating that these resemble
      filopodia growing from the plasma membrane. The combination of PI(4,5)P2 and
      phosphatidylinositol 3-phosphate in curved liposomes or supported bilayers on
      glass nanospheres uses Snx9, Cdc42, N-WASP (neuronal-Wiskott-Aldrich syndrome
      protein), and Arp2/3 complex for actin polymerization suggesting that this
      membrane may mimic the progression from plasma membrane to endosomes. Here we
      describe how to prepare high-speed supernatant frog egg extracts and
      phosphoinositide-containing liposomes and supported lipid bilayers that can
      assemble actin structures. We also describe the methods we use to assay actin
      polymerization using microscopy and spectrofluorometry and our protocol for
      immunodepleting specific proteins from extracts. 

PMID- 25997347
TI  - Reconstituting geometry-modulated protein patterns in membrane compartments.
AB  - The MinCDE protein system from Escherichia coli has become one of the most
      striking paradigms of protein self-organization and biological pattern formation.
      The whole set of Min proteins is functionally active to position the divisome
      machinery by inhibiting Z ring assembly away from mid-cell. This is accomplished
      by an oscillation behavior between the cell poles, induced by the reaction
      between the two antagonistic proteins MinD and MinE, which has long caught the
      attention of quantitative biologists. Technical advances in fluorescence
      microscopy and molecular biology have allowed us in the past years to
      reconstitute this MinDE self-organization in cell-free environments on model
      membranes. We verified the compositional simplicity of protein systems
      principally required for biological pattern formation, and subjected the
      mechanism to quantitative biophysical analysis on a single-molecule level. On
      flat extended membranes, MinD and MinE self-organized into parallel propagating
      waves. Moreover, employing microsystems technology to construct membrane-clad
      soft polymer compartments mimicking the shape of native E. coli cells has further
      enabled us to faithfully reproduce Min protein oscillations. We further
      investigated the response of this self-organizing molecular system to three
      dimensional compartment geometry. We could show that Min protein patterns depend
      strongly on the size and shape of the compartment, and the oscillation axis can
      only be preserved within a certain length interval and narrow width of the
      compartment. This renders the Min system a perfectly adapted oscillator to the
      bacterial cell geometry. 

PMID- 25997349
TI  - Building interconnected membrane networks.
AB  - Reconstituted replica cell membranes are easily created by contacting two lipid
      monolayer-encased aqueous droplets under an oil phase. Called the droplet
      interface bilayer (DIB), this technique has been used to study a wide range of
      membrane processes. Importantly, this method is compatible with electrical
      measurements, meaning that membrane protein activities are easily observed in
      DIBs. By positioning droplets in two- and three-dimensional networks,
      sophisticated interconnected systems can be created that possess collective
      properties. The methods described here summarize the approaches used to create
      DIB networks and how to operate the devices that have been constructed so far. 

PMID- 25997348
TI  - Structural and functional studies of membrane remodeling machines.
AB  - Building cells from their component parts will hinge upon our ability to
      reconstitute biochemical compartmentalization and exchange between membrane
      delimited organelles. By contrast with our understanding of other cellular
      events, the mechanisms that govern membrane trafficking has lagged because the
      presence of phospholipid bilayers complicates the use of standard methods. This
      chapter describes in vitro methods for purifying, reconstituting, and visualizing
      membrane remodeling activities directly by electron cryomicroscopy. 

PMID- 25997351
TI  - Reconstituting ParA/ParB-mediated transport of DNA cargo.
AB  - Protein gradients play key roles in subcellular spatial organization. In
      bacteria, ParA adenosine triphosphatases, or ATPases, form dynamic gradients on
      the nucleoid surface, which imparts positional information for the segregation,
      transport, and positioning of chromosomes, plasmids, and large protein
      assemblies. Despite the apparent simplicity of these minimal and self-organizing
      systems, the mechanism remains unclear. The small size of bacteria along with the
      number of physical and biochemical processes involved in subcellular organization
      makes it difficult to study these systems under controlled conditions in vivo. We
      developed a cell-free reconstitution technique that allows for the visualization
      of ParA-mediated cargo transport on a DNA carpet, which acts as a biomimetic of
      the nucleoid surface. Here, we present methods to express, purify, and visualize
      the dynamic properties of the SopABC system from F plasmid, considered a paradigm
      for the study of ParA-type systems. We hope similar cell-free studies will be
      used to address the biochemical and biophysical underpinnings of this ubiquitous
      transport scheme in bacteria. 

PMID- 25997350
TI  - Using supported bilayers to study the spatiotemporal organization of membrane
      bound proteins.
AB  - Cell division in prokaryotes and eukaryotes is commonly initiated by the well
      controlled binding of proteins to the cytoplasmic side of the cell membrane.
      However, a precise characterization of the spatiotemporal dynamics of membrane
      bound proteins is often difficult to achieve in vivo. Here, we present protocols
      for the use of supported lipid bilayers to rebuild the cytokinetic machineries of
      cells with greatly different dimensions: the bacterium Escherichia coli and eggs
      of the vertebrate Xenopus laevis. Combined with total internal reflection
      fluorescence microscopy, these experimental setups allow for precise quantitative
      analyses of membrane-bound proteins. The protocols described to obtain glass
      supported membranes from bacterial and vertebrate lipids can be used as starting
      points for other reconstitution experiments. We believe that similar biochemical
      assays will be instrumental to study the biochemistry and biophysics underlying a
      variety of complex cellular tasks, such as signaling, vesicle trafficking, and
      cell motility. 

PMID- 25997352
TI  - Cell-sized liposomes that mimic cell motility and the cell cortex.
AB  - Cells move and change shape by dynamically reorganizing their cytoskeleton next
      to the plasma membrane. In particular, actin assembly generates forces and
      stresses that deform the cell membrane. Cell-sized liposomes are designed to
      mimic this function. The activation of actin polymerization at their membrane is
      able to push the membrane forward, thus reproducing the mechanism of
      lamellipodium extension at the cell front. Moreover, the cell cortex, a
      submicrometer-thick actin shell right beneath the cell membrane can be
      reproduced; it contributes to cell tension with the action of molecular motors.
      We will describe experimental methods to prepare liposomes that mimic the inside
      geometry of a cell, and that reproduce actin-based propulsion of the liposome
      using an outside geometry. Such systems allow to study how actin-related proteins
      control and affect actin cortex assembly and can produce forces that drive cell
      shape changes. 

PMID- 25997353
TI  - Reconstitution of cortical actin networks within water-in-oil emulsions.
AB  - We describe the reconstitution of dynamic cortical actin networks within cell
      like compartments. The approach is based on encapsulation of Xenopus egg extract
      within water-in-oil emulsions. The growth of cortical actin networks is catalyzed
      by an amphiphilic actin nucleation-promoting factor that localizes to the
      water/oil interface. We first describe the preparation of cell-free Xenopus egg
      extract that provides all the soluble components of the actin machinery. We then
      describe the preparation of the amphiphilic, fluorescent actin nucleation
      promoting factor that directs actin polymerization to the interface. Finally, we
      describe the steps required for assembly of dynamic actin cortices within water
      in-oil emulsions, including the emulsification process and the sample preparation
      procedures. We provide recommendations for handling sensitive system components
      and discuss potential uses of this reconstitution approach for cytoskeletal
      research. 

PMID- 25997354
TI  - Engineering artificial cells by combining HeLa-based cell-free expression and
      ultrathin double emulsion template.
AB  - Generation of artificial cells provides the bridge needed to cover the gap
      between studying the complexity of biological processes in whole cells and
      studying these same processes in an in vitro reconstituted system. Artificial
      cells are defined as the encapsulation of biologically active material in a
      biological or synthetic membrane. Here, we describe a robust and general method
      to produce artificial cells for the purpose of mimicking one or more behaviors of
      a cell. A microfluidic double emulsion system is used to encapsulate a mammalian
      cell-free expression system that is able to express membrane proteins into the
      bilayer or soluble proteins inside the vesicles. The development of a robust
      platform that allows the assembly of artificial cells is valuable in
      understanding subcellular functions and emergent behaviors in a more cell-like
      environment as well as for creating novel signaling pathways to achieve specific
      cellular behaviors. 

PMID- 25997355
TI  - Reconstitution of proteins on electroformed giant unilamellar vesicles.
AB  - In vitro reconstitution of simplified biological systems from molecular parts has
      proven to be a powerful method for investigating the biochemical and biophysical
      principles underlying cellular processes. In recent years, there has been a
      growing interest in reconstitution of protein-membrane interactions to understand
      the critical role played by membranes in organizing molecular-scale events into
      micron-scale patterns and protrusions. However, while all reconstitution
      experiments depend on identifying and isolating an essential set of soluble
      biomolecules, such as proteins, DNA, and RNA, reconstitution of membrane-based
      processes involves the additional challenge of forming and working with lipid
      bilayer membranes with composition, fluidity, and mechanical properties
      appropriate for the process at hand. Here we discuss a selection of methods for
      forming synthetic lipid bilayer membranes and present a versatile
      electroformation protocol that our lab uses for reconstituting proteins on giant
      unilamellar vesicles. This synthetic membrane-based approach to reconstitution
      offers the ability to study protein organization and activity at membranes under
      more cell-like conditions, addressing a central challenge to accomplishing the
      grand goal of "building the cell." 

PMID- 25997357
TI  - Surgical treatment of severe laryngomalacia: Six month follow up.
AB  - BACKGROUND: Laryngomalacia (LM) is the most common congenital anomaly of larynx
      that causes stridor in children. We evaluated the efficacy of epiglottic suture
      and laser epiglottopexy for treatment of infants with severe LM. METHODS:
      Surgical intervention was performed in 19 patients with severe LM, after the
      diagnosis was established using flexible laryngotracheobronchoscopy. Five
      patients had isolated type 1 LM, and 14 patients had a combination of type 1 and
      3 LM. Indication for surgical treatment was the presence of LM with at least one
      of the following: malnutrition (body mass index [BMI] Z score < -2 SD), dysphagia
      or symptoms of gastroesophageal reflux and mean oxygen saturation (SaO2 ) <92%
      with oxygen desaturation index (ODI) > 3. RESULTS: Epiglottic suture was
      performed in 11 patients, and laser epiglottopexy in eight, at mean age 3.95 +/-
      2.4 months. Rate of operation was 2.2-fold greater for more severe anomaly
      (combination of type 1 and 3 LM) than for isolated type 1. At 6 month follow up
      symptoms had gradually improved, as well as nutritional status, with increase of
      mean BMI Z score from -3.7 to -0.9 (P < 0.01). Mean preoperative SaO2 was 89.4 +/
      4.3% with mean ODI of 5.8. At 6 month follow up, mean SaO2 was 96.7 +/- 1.1%,
      and mean ODI was 1.2 (P < 0.01). CONCLUSIONS: Epiglottic suture and laser
      epiglottopexy are efficient surgical techniques that lead to significant
      improvement of symptoms, oxygenation and nutritional status in patients with LM.

PMID- 25997356
TI  - Reconstituting SNARE-mediated membrane fusion at the single liposome level.
AB  - Successful reconstitutions of SNARE-mediated intracellular membrane fusion have
      been achieved in bulk fusion assays since 1998 and in single liposome fusion
      assays since 2004. Especially in neuronal presynaptic SNARE-mediated exocytosis,
      fusion is controlled by numerous accessory proteins, of which some functions have
      also been reconstituted in vitro. The development of and results obtained with
      two fundamentally different single liposome fusion assays, namely liposome-to
      supported membrane and liposome-to-liposome, are reviewed. Both assays
      distinguish between liposome docking and fusion steps of the overall fusion
      reaction and both assays are capable of resolving hemi-and full-fusion
      intermediates and end states. They have opened new windows for elucidating the
      mechanisms of these fundamentally important cellular reactions with unprecedented
      time and molecular resolution. Although many of the molecular actors in this
      process have been discovered, we have only scratched the surface of looking at
      their fascinating plays, interactions, and choreographies that lead to vesicle
      traffic as well as neurotransmitter and hormone release in the cell. 

PMID- 25997358
TI  - Adaptation of faecal microbiota in sows after diet changes and consequences for
      in vitro fermentation capacity.
AB  - In vitro gas production studies are routinely used to assess the metabolic
      capacity of intestinal microbiota to ferment dietary fibre sources. The faecal
      inocula used during the in vitro gas production procedure are most often obtained
      from animals adapted to a certain diet. The present study was designed to assess
      whether 19 days of adaptation to a diet are sufficient for faecal inocula of pigs
      to reach a stable microbial composition and activity as determined by in vitro
      gas production. Eighteen multiparous sows were allotted to one of two treatments
      for three weeks: a diet high in fibre (H) or a diet low in fibre (L). After this
      3-week period, the H group was transferred to the low fibre diet (HL-treatment)
      while the L group was transferred to the diet high in fibre (LH-treatment).
      Faecal samples were collected from each sow at 1, 4, 7, 10, 13, 16 and 19 days
      after the diet change and prepared as inoculum used for incubation with three
      contrasting fermentable substrates: oligofructose, soya pectin and cellulose. In
      addition, inocula were characterised using a phylogenetic microarray targeting
      the pig gastrointestinal tract microbiota. Time after diet change had an effect
      (P<0.05) on total gas production for the medium-fast fermentable substrates; soya
      pectin and oligofructose. For the more slowly fermentable cellulose, all measured
      fermentation parameters were consistently higher (P<0.05) for animals in the HL
      treatment. Diet changes led to significant changes in relative abundance of
      specific bacteria, especially for members of the Bacteroidetes and Bacilli,
      which, respectively, increased or decreased for the LH-treatment, while changes
      were opposite for the HL-treatment. Changing the diet of sows led to changes in
      fermentation activity of the faecal microbiota and in composition of the
      microbiota over time. Adaptation of the microbiota as assessed by gas production
      occurred faster for LH-animals for fast fermentable substrates compared with HL
      animals. Overall, adaptation of the large intestinal microbiota of sows as a
      result of ingestion of low and high fibre diets seems to take longer than 19
      days, especially for the ability to ferment slowly fermentable substrates. 

PMID- 25997359
TI  - Comparative Shotgun Proteomic Analysis of Wastewater-Cultured Microalgae:
      Nitrogen Sensing and Carbon Fixation for Growth and Nutrient Removal in
      Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii was batch-cultured for 12 days under continuous
      illumination to investigate nitrogen uptake and metabolic responses to wastewater
      processing. Our approach compared two conditions: (1) artificial wastewater
      containing nitrate and ammonia and (2) nutrient-sufficient control containing
      nitrate as sole form of nitrogen. Treatments did not differ in final biomass;
      however, comparison of group proteomes revealed significant differences. Label
      free shotgun proteomic analysis identified 2358 proteins, of which 92 were
      significantly differentially abundant. Wastewater cells showed higher relative
      abundances of photosynthetic antenna proteins, enzymes related to carbon
      fixation, and biosynthesis of amino acids and secondary metabolites. Control
      cells showed higher abundances of enzymes and proteins related to nitrogen
      metabolism and assimilation, synthesis and utilization of starch, amino acid
      recycling, evidence of oxidative stress, and little lipid biosynthesis. This
      study of the eukaryotic microalgal proteome response to nitrogen source,
      availability, and switching highlights tightly controlled pathways essential to
      the maintenance of culture health and productivity in concert with light
      absorption and carbon assimilation. Enriched pathways in artificial wastewater,
      notably, photosynthetic carbon fixation and biosynthesis of plant hormones, and
      those in nitrate only control, most notably, nitrogen, amino acid, and starch
      metabolism, represent potential targets for genetic improvement requiring
      targeted elucidation. 

PMID- 25997361
TI  - Mapping opportunities and challenges for rewilding in Europe.
AB  - Farmland abandonment takes place across the world due to socio-economic and
      ecological drivers. In Europe agricultural and environmental policies aim to
      prevent abandonment and halt ecological succession. Ecological rewilding has been
      recently proposed as an alternative strategy. We developed a framework to assess
      opportunities for rewilding across different dimensions of wilderness in Europe.
      We mapped artificial light, human accessibility based on transport
      infrastructure, proportion of harvested primary productivity (i.e., ecosystem
      productivity appropriated by humans through agriculture or forestry), and
      deviation from potential natural vegetation in areas projected to be abandoned by
      2040. At the continental level, the levels of artificial light were low and the
      deviation from potential natural vegetation was high in areas of abandonment. The
      relative importance of wilderness metrics differed regionally and was strongly
      connected to local environmental and socio-economic contexts. Large areas of
      projected abandonment were often located in or around Natura 2000 sites. Based on
      these results, we argue that management should be tailored to restore the aspects
      of wilderness that are lacking in each region. There are many remaining
      challenges regarding biodiversity in Europe, but megafauna species are already
      recovering. To further potentiate large-scale rewilding, Natura 2000 management
      would need to incorporate rewilding approaches. Our framework can be applied to
      assessing rewilding opportunities and challenges in other world regions, and our
      results could guide redirection of subsidies to manage social-ecological systems.

PMID- 25997360
TI  - Temporal and spatial association of Streptococcus suis infection in humans and
      porcine reproductive and respiratory syndrome outbreaks in pigs in northern
      Vietnam.
AB  - Porcine reproductive and respiratory syndrome (PRRS) outbreaks in pigs are
      associated with increased susceptibility of pigs to secondary bacterial
      infections, including Streptococcus suis - an important zoonotic pathogen causing
      bacterial meningitis in humans. This case-control study examined the association
      between human S. suis infection and PRRS outbreaks in pigs in northern Vietnam.
      We included 90 S. suis case-patients and 183 non-S. suis sepsis controls from a
      referral hospital in Hanoi in 2010, a period of major PRRS epizootics in Vietnam.
      PRRS exposure was determined using data from the National Centre of Veterinary
      Diagnosis. By univariate analysis, significantly more S. suis patients were
      reported residing in or adjacent to a PRRS district compared to controls [odds
      ratio (OR) 2.82, 95% confidence interval (CI) 1.35-5.89 and OR 3.15, 95% CI 1.62
      6.15, respectively]. Only residency in adjacent districts remained significantly
      associated with risk of S. suis infection after adjusting for sex, occupation,
      and eating practices. SaTScan analysis showed a possible cluster of S. suis
      infection in humans around PRRS confirmed locations during the March-August
      period. The findings indicate an epidemiological association between PRRS in pigs
      and S. suis infections in humans. Effective strategies to strengthen control of
      PRRS in pigs may help reduce transmission of S. suis infection to humans. 

PMID- 25997362
TI  - Epinephrine doses delivered from auto-injectors stored at excessively high
      temperatures.
AB  - CONTEXT: Prompt injection of epinephrine (adrenaline) from epinephrine auto
      injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital
      settings. Storage of EAIs at room temperature (25  degrees C) is advised;
      however, storage at excessively high temperatures sometimes occurs. To our
      knowledge, there are no previous publications on the doses of epinephrine ejected
      from EAIs after storage at such temperatures. OBJECTIVE: We examined the
      epinephrine doses delivered from activated EAIs stored constantly or cyclically
      at 70  degrees C. METHODS: Twenty-five in-date EAIs were stored constantly or
      cyclically at 70  degrees C (excessive heat) or 25  degrees C (controls) for 5 d
      or 10 d. EAIs were activated and the epinephrine doses in the ejected solutions
      were measured using HPLC-UV. The enantiomeric purity of epinephrine was also
      measured by HPLC-UV. RESULTS: Control EAIs ejected a volume of 0.300 +/- 0.006 mL
      containing 103.7 +/- 3.3% of labeled dose (LD). After 5 d or 10 d of constant
      storage at 70  degrees C and activation at 70  degrees C, EAIs ejected a volume
      of 0.367 +/- 0.008 mL containing 96.8 +/- 3.8% LD and 0.373 +/- 0.007 mL
      containing 77.7 +/- 3.3% LD, respectively. After 5 d of cyclic storage at 70 
      degrees C and cooling to 25  degrees C before activation, EAIs ejected a volume
      of 0.311 +/- 0.008 mL containing 87.2 +/- 1.9% LD. Under the experimental
      conditions of this study, the resultant chromatographic peaks of epinephrine
      solutions from all EAIs represented only the pure l-enantiomer of epinephrine.
      CONCLUSION: EAIs should be stored under recommended conditions of the
      manufacturer. EAIs stored at excessively high temperatures cannot be used to
      treat humans while still hot, and when cooled, cannot be relied on to deliver the
      labeled epinephrine dose in anaphylaxis.

PMID- 25997363
TI  - Influence of pressurized carbon dioxide on ketoprofen-incorporated hot-melt
      extruded low molecular weight hydroxypropylcellulose.
AB  - OBJECTIVES: The aim of the current research project was to investigate the effect
      of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of
      ketoprofen (KTP)-incorporated hydroxypropylcellulose (HPC) (KlucelTM ELF, EF, and
      LF) produced using hot-melt extrusion (HME) techniques and to assess the
      plasticization effect of P-CO2 on the various polymers tested. METHODS: The
      physico-mechanical properties of extrudates with and without injection of P-CO2
      were examined and compared with extrudates with the addition of 5% liquid
      plasticizer of propylene glycol (PG). The extrudates were milled and compressed
      into tablets. Tablet characteristics of the extrudates with and without injection
      of P-CO2 were evaluated. RESULTS AND CONCLUSION: P-CO2 acted as a plasticizer for
      tested polymers, which allowed for the reduction in extrusion processing
      temperature. The microscopic morphology of the extrudates was changed to a foam
      like structure due to the expansion of the CO2 at the extrusion die. The foamy
      extrudates demonstrated enhanced KTP release compared with the extrudates
      processed without P-CO2 due to the increase of porosity and surface area of those
      extrudates. Furthermore, the hardness of the tablets prepared by foamy extrudates
      was increased and the percent friability was decreased. Thus, the good binding
      properties and compressibility of the extrudates were positively influenced by
      utilizing P-CO2 processing.

PMID- 25997364
TI  - Latent structure analysis in the pharmaceutical process of tablets prepared by
      wet granulation.
AB  - BACKGROUND: Granule characteristics are some of the important intermediate
      qualities that determine tablet properties. However, the relationships between
      granule and tablet characteristics are poorly understood. The aim of this study
      was to elucidate relationships among formulation factors, granule
      characteristics, and tablet properties using a non-linear response surface method
      (RSM) incorporating a thin-plate spline interpolation (RSM-S) and a Bayesian
      network (BN). METHOD: Tablets containing lactose (Lac), cornstarch (CS), and
      microcrystalline cellulose (MCC) were prepared by wet granulation. Ten
      formulations were prepared by an extreme vertices design. The angle of repose
      (Y1), compressibility (Y2), cohesion force (Y3), internal friction angle (Y4),
      and mean particle size (Y5) were measured as granule characteristics. Tensile
      strength (TS) and disintegration time (DT) were measured as tablet properties.
      RESULTS: RSM-S results showed that TS increased with increasing amounts of MCC
      and Lac. DT decreased with increasing amounts of MCC and CS. The optimal BN
      models were predicted using four evaluation indices -Y3 was shown to be the most
      important factor for TS, whereas Y2, Y3, and Y4 were relatively important for
      predicting DT. Moreover, tablets with excellent tablet properties (i.e. high TS
      and low DT) were produced by relatively high Y1, low Y2, high Y3, high Y4, and
      middle Y5 values, and resulted from the middle of MCC, middle-to-low CS, low Lac,
      and middle-to-low magnesium stearate (Mg-St) amounts. CONCLUSION: The RSM-S and
      BN techniques are useful for revealing complex relationships among formulation
      factors, granule characteristics, and tablet properties.

PMID- 25997365
TI  - Emerging therapies for the treatment of ungual onychomycosis.
AB  - INTRODUCTION: Onychomycosis, a common fungal infection in the finger and toe
      nails, affects approximately 2-8% of the worldwide population. Fungal infection
      is more complicated in those who suffer from conditions, such as diabetes,
      peripheral vascular diseases and compromised immune diseases. AREA COVERED:
      Onychomycosis treatment has been classified on the basis of location of infection
      in the toes and fingers and infectious agents (dermatophytes fungi, yeast and non
      dermatophyte molds). In this review, the available therapies (traditional and
      device based) and their limitations for the treatment of onychomycosis have been
      discussed. EXPERT OPINION: The success rate with topical nail products has been
      minimal. The main reason for this poor success rate could be attributed to the
      lack of complete understanding of the pathophysiology of the disease and clinical
      pharmacokinetic data of drugs in the infected nail apparatus.

PMID- 25997366
TI  - Targeting the Early Step of Building Block Organization in Viral Capsid Assembly.
AB  - Viral assembly, similar to other self-organizing protein systems, relies upon
      early building blocks, which associate into the late supramolecular structures.
      An initial and crucial event during HIV-1 core assembly is the dimerization of
      the capsid protein C-terminal domain, which stabilizes the viral capsid lattice.
      Thus, monitoring and manipulating this stage is desirable both from mechanistic
      as well as clinical perspectives. Here, we developed a fluorescent-based method
      for the detection and visualization of these early capsid interactions. We
      detected strong dimeric interactions, which were influenced by mutations in the
      capsid protein. We utilized this assay for potential assembly inhibitors
      screening, which resulted in the identification of a leading compound that
      hinders the assembly of capsid protein in vitro. Moreover, a derivative of the
      compound impaired virus production and infectivity in cell cultures. These
      findings demonstrate that the described assay efficiently detects the very first
      association events in HIV-1 capsid formation and emphasize the significance of
      targeting early intermolecular interactions. 

PMID- 25997367
TI  - Whole-genome prediction of fatty acid composition in meat of Japanese Black
      cattle.
AB  - Because fatty acid composition influences the flavor and texture of meat,
      controlling it is particularly important for cattle breeds such as the Japanese
      Black, characterized by high meat quality. We evaluated the predictive ability of
      single-step genomic best linear unbiased prediction (ssGBLUP) in fatty acid
      composition of Japanese Black cattle by assessing the composition of seven fatty
      acids in 3088 cattle, of which 952 had genome-wide marker genotypes. All sires of
      the genotyped animals were genotyped, but their dams were not. Cross-validation
      was conducted for the 952 animals. The prediction accuracy was higher with
      ssGBLUP than with best linear unbiased prediction (BLUP) for all traits, and in
      an empirical investigation, the gain in accuracy of using ssGBLUP over BLUP
      increased as the deviations in phenotypic values of the animals increased. In
      addition, the superior accuracy of ssGBLUP tended to be more evident in animals
      whose maternal grandsire was genotyped than in other animals, although the effect
      was small. 

PMID- 25997368
TI  - Elevated temperature inhibits recruitment of transferrin-positive vesicles and
      induces iron-deficiency genes expression in Aiptasia pulchella host-harbored
      Symbiodinium.
AB  - Coral bleaching is the consequence of disruption of the mutualistic Cnidaria
      dinoflagellate association. Elevated seawater temperatures have been proposed as
      the most likely cause of coral bleaching whose severity is enhanced by a
      limitation in the bioavailability of iron. Iron is required by numerous organisms
      including the zooxanthellae residing inside the symbiosome of cnidarian cells.
      However, the knowledge of how symbiotic zooxanthellae obtain iron from the host
      cells and how elevated water temperature affects the association is very limited.
      Since cellular iron acquisition is known to be mediated through transferrin
      receptor-mediated endocytosis, a vesicular trafficking pathway specifically
      regulated by Rab4 and Rab5, we set out to examine the roles of these key proteins
      in the iron acquisition by the symbiotic Symbiodinium. Thus, we hypothesized that
      the iron recruitments into symbiotic zooxanthellae-housed symbiosomes may be
      dependent on rab4/rab5-mediated fusion with vesicles containing iron-bound
      transferrins and will be retarded under elevated temperature. In this study, we
      cloned a novel monolobal transferrin (ApTF) gene from the tropical sea anemone
      Aiptasia pulchella and confirmed that the association of ApTF with A. pulchella
      Rab4 (ApRab4) or A. pulchella Rab5 (ApRab5) vesicles is inhibited by elevated
      temperature through immunofluorescence analysis. We confirmed the iron-deficient
      phenomenon by demonstrating the induced overexpression of iron-deficiency
      responsive genes, flavodoxin and high-affinity iron permease 1, and reduced
      intracellular iron concentration in zooxanthellae under desferrioxamine B (iron
      chelator) and high temperature treatment. In conclusion, our data are consistent
      with algal iron deficiency being a contributing factor for the thermal stress
      induced bleaching of symbiotic cnidarians. 

PMID- 25997369
TI  - Reply: To PMID 25579887.

PMID- 25997370
TI  - Reply: To PMID 25891989.

PMID- 25997371
TI  - Risk stratification of contrast-induced acute kidney injury after percutaneous
      coronary intervention: should we finally get rid of procedural variables?

PMID- 25997372
TI  - Separation of sources in radiofrequency measurements of partial discharges using
      time-power ratio maps.
AB  - Partial discharges measurement is one of the most useful tools for condition
      monitoring of high-voltage (HV) equipment. These phenomena can be measured on
      line in radiofrequency (RF) with sensors such as the Vivaldi antenna, used in
      this paper, which improves the signal-to-noise ratio by rejecting FM and low
      frequency TV bands. Additionally, the power ratios (PR), a signal-processing
      technique based on the power distribution of the incoming signals in frequency
      bands, are used to characterize different sources of PD and electromagnetic noise
      (EMN). The calculation of the time length of the pulses is introduced to separate
      signals where the PR alone do not give a conclusive solution. Thus, if several EM
      sources could be previously calibrated, it is possible to detect pulses
      corresponding to PD activity. 

PMID- 25997373
TI  - Pharmacokinetics and cardiovascular effects following a single oral
      administration of a nonaqueous pimobendan solution in healthy dogs.
AB  - Pimobendan is an inodilator used in the treatment of canine congestive heart
      failure (CHF). The aim of this study was to investigate the pharmacokinetics and
      cardiovascular effects of a nonaqueous oral solution of pimobendan using a single
      dose, operator-blinded, parallel-dose study design. Eight healthy dogs were
      divided into two treatment groups consisting of water (negative control) and
      pimobendan solution. Plasma samples and noninvasive measures of cardiovascular
      function were obtained over a 24-h period following dosing. Pimobendan and its
      active metabolite were quantified using an ultra-high-performance liquid
      chromatography-mass spectrometer (UHPLC-MS) assay. The oral pimobendan solution
      was rapidly absorbed [time taken to reach maximum concentration (Tmax ) 1.1 h]
      and readily converted to the active metabolite (metabolite Tmax 1.3 h). The
      elimination half-life was short for both pimobendan and its active metabolite
      (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2-4 h
      after a single oral dose, with measurable effects occurring primarily in
      echocardiographic indices of systolic function. Significant effects persisted for
      <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.

PMID- 25997374
TI  - To clamp or not to clamp during partial nephrectomy.

PMID- 25997375
TI  - Patient engagement and the design of digital health.

PMID- 25997376
TI  - Synovial sarcoma mimicking thyroid carcinoma.

PMID- 25997377
TI  - Evaluation of different inactivation methods for high and low pathogenic avian
      influenza viruses in egg-fluids for antigen preparation.
AB  - In view of the emerging avian influenza (AI) viruses, it is important to study
      the susceptibility of AI viruses to inactivating agents for preparation of
      antigens and inactivated vaccines. The available information on susceptibility of
      both the high and low pathogenic AI viruses to different inactivating agents is
      inadequate and ambiguous. It has been shown that different subtypes of influenza
      viruses require different physical and chemical conditions for inactivation of
      infectivity. The present study was undertaken to evaluate the use of beta
      propiolactone (BPL), formalin and ether for inactivation and its impact on
      antigenicity of AI viruses. A total of nine high and low pathogenic AI viruses
      belonging to four influenza A subtypes were included in the study. The H5N1
      viruses were from the clades 2.2, 2.3.2.1 and 2.3.4. The H9N2 virus included in
      the study was of the G1 genotype, while the H11N1 and H4N6 viruses were from the
      Eurasian lineage. The viruses were treated with BPL, formalin and with ether. The
      confirmation of virus inactivation was performed by two serial passages of
      inactivated viruses in embryonated chicken eggs. The infectivity of all tested AI
      viruses was eliminated using 0.1% BPL and 0.1% formalin. Ether eliminated
      infectivity of all tested low pathogenic AI viruses; however, ether with 0.2% or
      0.5% Tween-20 was required for inactivation of the highly pathogenic AI H5N1
      viruses. Treatment with BPL, ether and formalin retained virus hemagglutination
      (HA) titers. Interestingly ether treatment resulted in significant rise in HA
      titers (P<0.05) of all tested AI viruses. This data demonstrated the utility of
      BPL, formalin and ether for the inactivation of infectivity of AI viruses used in
      the study for the preparation of inactivated virus antigens for research and
      diagnosis of AI. 

PMID- 25997378
TI  - Cobalt(III) tetraaza-macrocyclic complexes as efficient catalyst for photoinduced
      hydrogen production in water: Theoretical investigation of the electronic
      structure of the reduced species and mechanistic insight.
AB  - We recently reported a very efficient homogeneous system for visible-light driven
      hydrogen production in water based on the cobalt(III) tetraaza-macrocyclic
      complex [Co(CR)Cl2](+) (1) (CR=2,12-dimethyl-3,7,11,17-tetra-azabicyclo(11.3.1)
      heptadeca-1(17),2,11,13,15-pentaene) as a noble metal-free catalyst, with
      [Ru(II)(bpy)3](2+) (Ru) as photosensitizer and ascorbate/ascorbic acid (HA(
      )/H2A) as a sacrificial electron donor and buffer (PhysChemChemPhys 2013, 15,
      17544). This catalyst presents the particularity to achieve very high turnover
      numbers (TONs) (up to 1000) at pH 4.0 at a relative high concentration (0.1mM)
      generating a large amount of hydrogen and having a long term stability. A similar
      activity was observed for the aquo derivative [Co(III)(CR)(H2O)2](3+) (2) due to
      substitution of chloro ligands by water molecule in water. In this work, the
      geometry and electronic structures of 2 and its analog [Zn(II)(CR)Cl](+) (3)
      derivative containing the redox innocent Zn(II) metal ion have been investigated
      by DFT calculations under various oxidation states. We also further studied the
      photocatalytic activity of this system and evaluated the influence of varying the
      relative concentration of the different components on the H2-evolving activity.
      Turnover numbers versus catalyst (TONCat) were found to be dependent on the
      catalyst concentration with the highest value of 1130 obtained at 0.05 mM.
      Interestingly, the analogous nickel derivative, [Ni(II)(CR)Cl2] (4), when tested
      under the same experimental conditions was found to be fully inactive for H2
      production. Nanosecond transient absorption spectroscopy measurements have
      revealed that the first electron-transfer steps of the photocatalytic H2
      evolution mechanism with the Ru/cobalt tetraaza/HA(-)/H2A system involve a
      reductive quenching of the excited state of the photosensitizer by ascorbate
      (kq=2.5*10(7) M(-1) s(-1)) followed by an electron transfer from the reduced
      photosensitizer to the catalyst (ket=1.4*10(9) M(-1) s(-1)). The reduced catalyst
      can then enter into the cycle of hydrogen evolution.

PMID- 25997379
TI  - Expression of alpha-synuclein during eye development of mice (Mus musculus),
      chick (Gallus gallus domisticus) and fish (Ctenopharyngodon idella) in a
      comparison study.
AB  - Synucleins are small proteins associated with neurodegenerative diseases, alpha
      synuclein is a Parkinson's disease-linked protein of ubiquitous expression in the
      central nervous system. This study aimed at the localization of alpha-synuclein
      during eye development of mice (Mus musculus), chick (Gallus gallus domisticus)
      and fish (Ctenopharyngodon idella) by immunohistochemical staining in a
      comparison study. The results showed that alpha-synuclein expression increased
      gradually with the development of ciliary body, iris, retina and cornea of mice
      at E17, P1, P3, P7 and chick at E5, E10, E15 with unequal appearance of alpha
      synuclein expression. Also, it was not detected in iridocorneal angle during eye
      development of mice and chick. Alpha-synuclein expression during fish eye
      development at P10, P15, P20 was not detected either in the ciliray body or Iris
      regions and it was pronounced with sharp signals in the highly specialized tissue
      of the iridocorneal angle at P20. Also, the expression was gradually increased
      from P15 to P20 in fish retina and cornea. The pattern of expression and
      distribution of alpha-synuclein during the development of ciliary body and iris
      of mice, chick and fish has not been previously characterized, The data concluded
      that alpha-synuclein has important cellular function during eye development of
      studied animals. 

PMID- 25997380
TI  - Choice, deliberation, violence: Mental capacity and criminal responsibility in
      personality disorder.
AB  - Personality disorder is associated with self-harm and suicide, as well as
      criminal offending and violence towards others. These behaviours overlap when the
      means chosen to self-harm or attempt suicide put others at risk. In such
      circumstances, an individual's mental state at one and the same time may be
      deemed to meet the conditions for criminal responsibility, and to warrant
      involuntary hospital admission. I explore this tension in how people with
      personality disorder are treated at the hands of the criminal and civil law
      respectively in England and Wales: they may be deemed sufficiently mentally well
      to be punished for their crimes, but not deemed sufficiently mentally well to
      retain the right to make their own decisions about matters of serious importance
      to their own lives, including whether or not to continue them. The article
      divides into four sections. After introducing this tension, Section 2 sketches
      the nature of personality disorder and the psychology underlying self-directed
      and other-directed violence. Section 3 addresses the questions of whether people
      with personality disorder who are violent, whether towards self or others,
      typically meet the conditions for criminal responsibility and mental capacity
      respectively, considering in particular whether their underlying desires and
      values, or their emotional distress, affect their mental capacity to make
      treatment decisions. Section 4 then considers what we might do to address the
      tension, within the confines of current legislation. Drawing on The Review of the
      Mental Health Act 1983, I argue that we are ethically justified in involuntarily
      admitting to hospital people with personality disorder who pose a serious risk to
      themselves only if we simultaneously undertake to offer genuine help for their
      future, in the form of appropriate treatment, social support, and better life
      opportunities - a provision which, as things stand in England and Wales, is
      sorely lacking. 

PMID- 25997382
TI  - The role of dietary coconut for the prevention and treatment of Alzheimer's
      disease: potential mechanisms of action.
AB  - Coconut, Cocos nucifera L., is a tree that is cultivated to provide a large
      number of products, although it is mainly grown for its nutritional and medicinal
      values. Coconut oil, derived from the coconut fruit, has been recognised
      historically as containing high levels of saturated fat; however, closer scrutiny
      suggests that coconut should be regarded more favourably. Unlike most other
      dietary fats that are high in long-chain fatty acids, coconut oil comprises
      medium-chain fatty acids (MCFA). MCFA are unique in that they are easily absorbed
      and metabolised by the liver, and can be converted to ketones. Ketone bodies are
      an important alternative energy source in the brain, and may be beneficial to
      people developing or already with memory impairment, as in Alzheimer's disease
      (AD). Coconut is classified as a highly nutritious 'functional food'. It is rich
      in dietary fibre, vitamins and minerals; however, notably, evidence is mounting
      to support the concept that coconut may be beneficial in the treatment of
      obesity, dyslipidaemia, elevated LDL, insulin resistance and hypertension - these
      are the risk factors for CVD and type 2 diabetes, and also for AD. In addition,
      phenolic compounds and hormones (cytokinins) found in coconut may assist in
      preventing the aggregation of amyloid-beta peptide, potentially inhibiting a key
      step in the pathogenesis of AD. The purpose of the present review was to explore
      the literature related to coconut, outlining the known mechanistic physiology,
      and to discuss the potential role of coconut supplementation as a therapeutic
      option in the prevention and management of AD. 

PMID- 25997381
TI  - Against a singular understanding of legal capacity: Criminal responsibility and
      the Convention on the Rights of Persons with Disabilities.
AB  - The United Nations Convention on the Rights of Persons with Disabilities (CRPD)
      is being used to argue for wider recognition of the legal capacity of people with
      mental disabilities. This raises a question about the implications of the
      Convention for attributions of criminal responsibility. The present paper works
      towards an answer by analysing the relationship between legal capacity in
      relation to personal decisions and criminal acts. Its central argument is that
      because moral and political considerations play an essential role in setting the
      relevant standards, legal capacity in the context of personal decisions and
      criminal acts should not be thought of as two sides of the same coin. The
      implications of particular moral or political norms are likely to be different in
      these two legal contexts, and this may justify asymmetries in the relevant
      standards for legal capacity. However, the analysis highlights a fundamental
      question about how much weight moral or political considerations should be given
      in setting these standards, and this is used to frame a challenge to those
      calling for significantly wider recognition of the legal capacity of people with
      mental disabilities on the basis of the Convention. 

PMID- 25997383
TI  - Blood donors--Serious adverse reactions (SAR) 2010-2014 EFS Chateauroux, France.
AB  - BACKGROUND: In 2013, the national French incidence of serious adverse reactions
      (SAR) was 155.7 per 100,000 donations and 82% of SAR were grade 2 (French
      classification of SAR related to blood donors) AIMS: The purpose of our study was
      to describe the profile of blood donator candidate which had a SAR in our center.
      METHODS: The study contains all the SAR superior to grade 1 occurred on the site
      EFS Chateauroux (site and mobile blood collection) from January 2010 to October
      31, 2014. We analyzed 37 parameters from the e-fit files (e-site French blood
      vigilance) and In-log software. RESULTS: We identified 82 SAR for 72,553 blood
      donations (incidence: 113.02 SAR per 100,000 donations). Forty-one men and 41
      women, middle age 39 years (18-66). Average height: 1.68 m (1.49-1.85); average
      weight: 68 kg (50-98); body mass index (kg/m(2)): 24,13(18.6-31.9). All donors
      were Caucasian and 30% unemployed. We found 74 vasovagal syncope (VVS), 5
      hematomas, 2 arterial injuries and an adverse reaction to citrate. In 90%, the
      SAR was immediate and of grade 2 in 85% of cases. Thirty-seven percent of SAR
      were first donation in connection with whole blood in 87% of cases. Regarding the
      seniority of donors, the number of average donations (whole blood, plasma,
      platelets) was 16.5. An SAR determined the stop of blood donation in 65% of cases
      with nearly 80% stoppage if it was a first donation. Seventy-three percent of SAR
      as a VVS took place during blood collection or within 5 minutes following the end
      of the donation. Sixty-one percent were men. Forty-four percent of cases were a
      first donation and 83% occurred in mobile blood collection. Average age was 36
      years. The result was a permanent stop of all type of donations in 76% of cases.
      Twenty-seven percent of SAR as a VVS took place beyond 5 minutes after the end of
      the donation. Seventy-five percent were women. Thirty percent of cases were a
      first donation and 95% of SAR occurred in mobile blood collection. Average age
      was 42 years. The result was a permanent stop of all type of donations in 40% of
      cases. CONCLUSIONS: When the SAR as a VVS occurs during or within 5 minutes
      following the end of the donation, it leads to a permanent stop of any type of
      donation in 76% of cases.

PMID- 25997384
TI  - An Extraperitoneal Technique for Murine Heterotopic Cardiac Transplantation.
AB  - The mouse heterotopic cardiac transplantation model has been used extensively by
      investigators in the field of organ transplantation to study the rejection
      process, test new antirejection treatments, tolerance induction protocols or to
      understand basic immunological principles. Due to its extensive use, any small
      refinement of the technique would have a major impact on replacement, reduction
      and refinement (commonly known as the 3Rs). Here, we describe a novel approach to
      refine this model. The donor aorta and pulmonary artery are anastomosed
      peripherally to the femoral artery and vein of the recipient, respectively. The
      technical success rate is comparable to the conventional abdominal site, but it
      avoids a laparotomy and handling of the bowels making it less invasive method. As
      a result, recipients recover faster and require less postoperative analgesia. It
      is a major refinement under one of the 3Rs and would represent an advance in
      animal welfare in scientific research. 

PMID- 25997385
TI  - Graphene oxide coated coordination polymer nanobelt composite material: a new
      type of visible light active and highly efficient photocatalyst for Cr(VI)
      reduction.
AB  - A visible light active photocatalyst was synthesized successfully by coating
      graphene oxide (GO) on a coordination polymer nanobelt (CPNB) using a simple
      colloidal blending process. Compared with neat CPNB, the resulting graphene oxide
      coated coordination polymer nanobelt composite material (GO/CPNB) exhibits
      excellent photocatalytic efficiency in the reduction of K2Cr2O7 under visible
      light irradiation. In the composite material, GO performs two functions. Firstly,
      it cuts down the band gap (E(g)) of the photocatalyst and extends its
      photoresponse region from the ultraviolet to visible light region. Secondly, GO
      exhibits excellent electron transportation ability that impedes its recombination
      with holes, and this can enhance photocatalytic efficiency. For GO, on its
      surface, the number of functional groups has a great influence on the
      photocatalytic performance of the resulting GO/CPNB composite material and an
      ideal GO"coater" to obtain a highly efficient GO/CPNB photocatalyst has been
      obtained. As a photocatalyst that may be used in the treatment of Cr(VI) in
      wastewater, GO/CPNB exhibited outstanding stability during the reduction of this
      pollutant.

PMID- 25997386
TI  - X4 Tropic Virus Prediction Is Associated with a Nadir CD4 T-Cell Count below 100
      Cells/mm.
AB  - OBJECTIVE: The aim of this study was to evaluate tropism prediction performances
      of three algorithms [geno2pheno false-positive rate 10% (G2P10), position
      specific scoring matrix (PSSM) and a combination of the 11/25 and net charge
      rules] and to investigate the viral and host factors potentially involved in the
      X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. METHODS:
      Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5
      antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120
      sequencing. In parallel, demographic, viral, immunological and clinical
      determinants were analyzed. RESULTS: According to the G2P10 algorithm, 48
      patients harbored X4 or X4R5 virus. The tropism prediction was concordant for
      87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of
      the 11/25 and net charge rules, respectively. X4 prediction was significantly
      associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss
      of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the
      nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01).
      CONCLUSION: We determined that the X4 virus detection is closely linked to the
      nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when
      considering a CCR5 antagonist therapy switch.

PMID- 25997387
TI  - Suppressor of cytokine signaling 1-modulated metalloproteinases and tissue
      inhibitor of metalloproteinase in pulmonary fibrosis.
AB  - An imbalance between metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) affects the synthesis and degradation of extracellular
      matrix molecules, which have an important role in the pathogenesis of pulmonary
      fibrosis. Lower mRNA expression levels of suppressor of cytokine signaling 1
      (SOCS1) are present in fibroblasts from the lungs of pulmonary fibrosis. However,
      little is currently known regarding the precise role of SOCS1 has in idiopathic
      pulmonary fibrosis (IPF). The present study examined the expression levels of
      MMPs and TIMPs in A549 human epithelial lung carcinoma cells and human embryonic
      lung fibroblasts (HLFs) stimulated with transforming growth factor-beta1 (TGF
      beta1) in conditions of deficiency and over-expression of SOCS1, by transfection
      with a lentivirus. Overexpression of SOCS1 in A549 cells and HLFs significantly
      inhibited the mRNA expression levels of MMP-1, MMP-2 and MMP-9 (P<0.05). In the
      A549 cells lacking SOCS1 expression, the mRNA expression levels of TIMP-1 were
      significantly higher compared with the control groups (P<0.01). Overexpression of
      SOCS1 partially reversed these changes. The expression levels of TIMP-1 in the
      HLFs with an overexpression of SOCS1 were decreased, as compared with the SOCS1
      deficient HLFs following TGF-beta1 stimulation; however, this finding was not
      significant (0.24+/-0.01 vs. 0.53+/-0.02, P>0.05). The expression levels of TIMP
      2 were significantly lower in the cells overexpressing SOCS1. Conversely, the
      mRNA expression levels of TIMP-2 were significantly higher in the SOCS1-deficient
      A549 cells, as compared with all of the other groups (P<0.05). TIMP-4 expression
      levels were elevated in the A549 cells and HLFs transfected with the SOCS1
      deficient lentivirus. The expression levels of TIMP-4 were significantly lower in
      the groups overexpressing SOCS1, as compared with the other groups. These results
      suggest that SOCS1 may act as a suppressor of pulmonary fibrosis, by reducing the
      expression of MMPs and TIMPs. Therefore, SOCS1 may be a target for IPF treatment.

PMID- 25997388
TI  - Noncalcifying variant of calcifying epithelial odontogenic tumor with Langerhans
      cells.

PMID- 25997389
TI  - Regulation of Photosynthesis during Abiotic Stress-Induced Photoinhibition.
AB  - Plants as sessile organisms are continuously exposed to abiotic stress conditions
      that impose numerous detrimental effects and cause tremendous loss of yield.
      Abiotic stresses, including high sunlight, confer serious damage on the
      photosynthetic machinery of plants. Photosystem II (PSII) is one of the most
      susceptible components of the photosynthetic machinery that bears the brunt of
      abiotic stress. In addition to the generation of reactive oxygen species (ROS) by
      abiotic stress, ROS can also result from the absorption of excessive sunlight by
      the light-harvesting complex. ROS can damage the photosynthetic apparatus,
      particularly PSII, resulting in photoinhibition due to an imbalance in the
      photosynthetic redox signaling pathways and the inhibition of PSII repair.
      Designing plants with improved abiotic stress tolerance will require a
      comprehensive understanding of ROS signaling and the regulatory functions of
      various components, including protein kinases, transcription factors, and
      phytohormones, in the responses of photosynthetic machinery to abiotic stress.
      Bioenergetics approaches, such as chlorophyll a transient kinetics analysis, have
      facilitated our understanding of plant vitality and the assessment of PSII
      efficiency under adverse environmental conditions. This review discusses the
      current understanding and indicates potential areas of further studies on the
      regulation of the photosynthetic machinery under abiotic stress. 

PMID- 25997390
TI  - Electroosmotic flow and Joule heating in preparative continuous annular
      electrochromatography.
AB  - An openFOAM "computational fluid dynamic" simulation model was developed for the
      description of local interaction of hydrodynamics and Joule heating in annular
      electrochromatography. A local decline of electrical conductivity of the
      background eluent is caused by an electrokinetic migration of ions resulting in
      higher Joule heat generation. The model equations consider the Navier-Stokes
      equation for incompressible fluids, the energy equation for stationary
      temperature fields, and the mass transfer equation for the electrokinetic flow.
      The simulations were embedded in commercial ANSYS Fluent software and in open
      source environment openFOAM. The annular gap (1 mm width) contained an inorganic
      C8 reverse-phase monolith as stationary phase prepared by an in situ sol-gel
      process. The process temperature generated by Joule heating was determined by
      thermal camera system. The local hydrodynamics in the prototype was detected by a
      gravimetric contact-free measurement method and experimental and simulated values
      matched quite well. 

PMID- 25997391
TI  - Synthetic pheromones as a management technique - dispensers reduce Linepithema
      humile activity in a commercial vineyard.
AB  - BACKGROUND: Invasive ants, such as the Argentine ant, have often been reported to
      facilitate honeydew-producing hemipteran pests such as mealybugs, which can be
      vectors of plant pathogens. Synthetic pheromones may offer a target-specific
      method to control such ants and consequently lower the abundance of honeydew
      producing pests. Here we report the results of a trial to suppress Argentine ants
      in grapevines using ant pheromone dispensers. RESULTS: Compared with untreated
      controls, we observed a significant drop in Argentine ant activity on the ground,
      irrespective of whether pheromone dispensers were placed at ground level, within
      the canopy or in both locations. Ant counts in the canopy confirmed that
      Argentine ant abundance was reduced under the influence of the pheromone
      dispenser placed at ground level compared with untreated controls. However,
      placing dispensers only in the canopy did not reduce the numbers of ants within
      the canopy compared with untreated controls. CONCLUSION: Our results showed that
      pheromone dispensers can significantly reduce Argentine ant foraging in
      grapevines if they are positioned appropriately. This technique could potentially
      reduce the abundance of associated mealybugs and potentially attendant virus
      vectoring areawide.

PMID- 25997392
TI  - EPAS1/HIF-2alpha is a driver of mammalian pexophagy.
AB  - Oxygen (O2) is an essential substrate in cellular metabolism and signaling and as
      such is linked to the survival and normal function of metazoans. Central to the
      molecular mechanisms underlying O2 homeostasis are hypoxia-inducible factors
      (HIFs), heterodimeric transcription factors composed of O2-regulated alpha
      subunits (HIF1A/HIF-1alpha or EPAS1/HIF-2alpha), and a constitutively expressed
      ARNT/HIF-1beta subunit, that serve as master regulators of the adaptive response
      to hypoxia. HIF1A and EPAS1 have both unique and overlapping functions in the
      regulation of diverse cellular processes, but so far there has been no evidence
      linking HIF signaling to peroxisomes. In a recent study we identified a unique
      function of EPAS1 as promoter of pexophagy in hepatocytes. Here we summarize our
      findings and discuss potential mechanisms by which EPAS1 might trigger pexophagy.

PMID- 25997393
TI  - Sentinel lymph node biopsy: in support of equity of access, informed shared
      decision making and patient choice.

PMID- 25997394
TI  - Quality of life and auditory performance in adults with asymmetric hearing loss.
AB  - We evaluated the relationship between binaural hearing deficits and quality of
      life. The study included 49 adults with asymmetric hearing loss (AHL), and 11
      adult normal-hearing listeners (NHL) served as controls. Speech reception
      thresholds (SRT) were assessed with the French Matrix Test. Quality of life was
      evaluated with the Speech, Spatial and Qualities of Hearing Scale (SSQ) and the
      Glasgow Health Status Inventory. Speech recognition in noise was significantly
      poorer for AHL subjects [-0.12 dB signal-to-noise ratio (SNR) in dichotic (with
      speech presented to the poorer ear and noise to the better ear), -1.72 dB in
      diotic and -6.84 dB in reverse-dichotic conditions] compared to NHL (-4.98 dB in
      diotic and -9.58 dB in dichotic conditions). Scores for quality-of-life
      questionnaires were significantly below norms. Significant correlations were
      found between the SRT for the dichotic condition and the SSQ total score (r = 
      0.38, p = 0.01), and pure-tone average thresholds for both groups.

PMID- 25997395
TI  - Roles of Mn-catalase and a possible heme peroxidase homologue in protection from
      oxidative stress in Thermus thermophilus.
AB  - Hydrogen peroxide (H2O2) produces hydroxyl radicals that directly attack a
      variety of biomolecules and cause severe cellular dysfunction. An extremely
      thermophilic bacterium, Thermus thermophilus HB8, possesses at least three
      enzymes that can scavenge H2O2: manganese-containing catalase (TTHA0122, MnCAT),
      a possible peroxiredoxin homologue (TTHA1300), and a possible heme peroxidase
      (HPX) homologue (TTHA1714). To investigate the roles of these proteins, we
      attempted to disrupt each of these genes in T. thermophilus HB8. Although we were
      able to completely disrupt ttha1300, we were unable to completely delete ttha0122
      and ttha1714 because of polyploidy. Quantitative real-time PCR showed that,
      compared to the wild type, 31 % of ttha0122 and 11 % of ttha1714 remained in the
      ?ttha0122 and ?ttha1714 disruption mutants, respectively. Mutants with reduced
      levels of ttha0122 or ttha1714 exhibited a significant increase in spontaneous
      mutation frequency. ?ttha1714 grew slower than the wild type under normal
      conditions. ?ttha0122 grew very poorly after exposure to H2O2. Moreover,
      ?ttha0122 did not show H2O2-scavenging activity, whereas ?ttha1300 and ?ttha1714
      scavenged H2O2, a property similar to that exhibited by the wild type. MnCAT
      purified from T. thermophilus HB8 cells scavenged H2O2 in vitro. The recombinant
      form of the possible HPX homologue, reconstituted with hemin, showed peroxidase
      activity with H2O2 as an oxidant substrate. Based on these results, we propose
      that not only MnCAT but also the possible HPX homologue is involved in protecting
      the cell from oxidative stress in T. thermophilus.

PMID- 25997397
TI  - A near-infrared fluorescent probe for the selective detection of HNO in living
      cells and in vivo.
AB  - Nitroxyl (HNO), the one-electron reduced and protonated analogue of nitric oxide
      (NO), demonstrates distinctive bio-pharmacological effects in the treatment of
      cardiovascular disorders. Herein, we design and synthesize a near-infrared (NIR)
      metal-free fluorescent probe Cyto-JN for the detection of nitroxyl (HNO) in
      living cells and in vivo. The metal-free Cyto-JN is composed of two moieties: the
      Aza-BODIPY fluorophore and the HNO recognition unit, the diphenylphosphinobenzoyl
      group. Cyto-JN can react with HNO in a 1 : 1 stoichiometry, which may bring great
      benefit to the detection efficiency of bioassays. Cyto-JN shows high sensitivity
      toward HNO and exhibits low cytotoxic effect on cells. Moreover, the probe
      displays good selectivity for the detection of HNO in the presence of various
      biologically related species. Cyto-JN can be applied successfully to bio-imaging
      of HNO in living cells and in mice. The results of flow cytometry confirm that
      the probe Cyto-JN can be used to detect intracellular HNO qualitatively and
      quantitatively. 

PMID- 25997396
TI  - Branched-chain alcohol formation by thermophilic bacteria within the genera of
      Thermoanaerobacter and Caldanaerobacter.
AB  - Fifty-six thermophilic strains including members of Caldanaerobacter,
      Caldicellulosiruptor, Caloramator, Clostridium, Thermoanaerobacter, and
      Thermoanaerobacterium, were investigated for branched-chain amino acid
      degradation in the presence of thiosulfate in batch culture. All of the
      Thermoanaerobacter and Caldanaerobacter strains (24) degraded the branched-chain
      amino acids (leucine, isoleucine, and valine) to a mixture of their corresponding
      branched-chain fatty acids and branched-chain alcohols. Only one Caloramator
      strain degraded the branched-chain amino acids to the corresponding branched
      chain fatty acids. The ratio of branched-chain fatty acid production over
      branched-chain alcohol production for Thermoanaerobacter was 7.15, 6.61, and
      11.53 for leucine, isoleucine, and valine, respectively. These values for
      Caldanaerobacter were 3.49, 4.13, and 7.31, respectively. This indicates that
      members within Caldanaerobacter produce proportionally more of the alcohols as
      compared with Thermoanaerobacter. No species within other genera investigated
      produced branched-chain alcohols from branched-chain amino acids in the presence
      of thiosulfate.

PMID- 25997398
TI  - Study of urinary 2-{[2-(acetylamino-2-carboxyethyl]sulfanyl}butanedioic acid, a
      mercapturic acid of rats treated with maleic acid.
AB  - Maleic anhydride was reported illegally adulterated into starch to prepare
      traditional foods for decades in Taiwan. Maleic acid (MA), hydrolyzed from maleic
      anhydride, could cause kidney damages to animals. The potential health effects
      due to long-term MA exposures through food consumption have been of great
      concerns. Assessment of the dietary MA exposures could be very difficult and
      complicated. One of the alternatives is to analyze an MA-specific biomarker to
      assess the daily total MA intake. Therefore, this paper aimed to study the
      mercapturic acid of MA, 2-{[2-(acetylamino)-2-carboxyethyl]sulfanyl}butanedioic
      acid (MAMA), with our newly-developed isotope-dilution online solid-phase
      extraction liquid chromatography tandem mass spectrometry (ID-SPE-LC-MS/MS)
      method. MAMA was first synthesized, purified, and characterized with NMR to
      reveal two diastereomers and used for developing the analytical method. The
      method was validated to reveal excellent sensitivity with a LOD at 16.3ng/mL and
      a LOQ at 20.6ng/mL and used to analyze MAMA in urine samples collected from
      Sprague-Dawley rats treated with a single dose of 0mg/kg, 6mg/kg, and 60mg/kg
      (n=5) of MA through gavage. Our results show dose-dependent increases in urinary
      MAMA contents, and 70% MAMA was excreted within 12h with no gender differences
      (p>0.05). A half life of urinary MAMA was estimated at 6.8h for rat. The
      formation of urinary MAMA validates it as a chemically-specific biomarker for
      current MA exposure. Future study of MA metabolism in vivo will elucidate
      mechanisms of MAMA formation, and analysis of this marker in epidemiology studies
      could help to shed light on the causal effects of MA on human. 

PMID- 25997399
TI  - Hydrodynamics of an electrochemical membrane bioreactor.
AB  - An electrochemical membrane bioreactor (EMBR) has recently been developed for
      energy recovery and wastewater treatment. The hydrodynamics of the EMBR would
      significantly affect the mass transfers and reaction kinetics, exerting a
      pronounced effect on reactor performance. However, only scarce information is
      available to date. In this study, the hydrodynamic characteristics of the EMBR
      were investigated through various approaches. Tracer tests were adopted to
      generate residence time distribution curves at various hydraulic residence times,
      and three hydraulic models were developed to simulate the results of tracer
      studies. In addition, the detailed flow patterns of the EMBR were acquired from a
      computational fluid dynamics (CFD) simulation. Compared to the tank-in-series and
      axial dispersion ones, the Martin model could describe hydraulic performance of
      the EBMR better. CFD simulation results clearly indicated the existence of a
      preferential or circuitous flow in the EMBR. Moreover, the possible locations of
      dead zones in the EMBR were visualized through the CFD simulation. Based on these
      results, the relationship between the reactor performance and the hydrodynamics
      of EMBR was further elucidated relative to the current generation. The results of
      this study would benefit the design, operation and optimization of the EMBR for
      simultaneous energy recovery and wastewater treatment. 

PMID- 25997400
TI  - Preoperative Endoscopy and Its Impact on Perioperative Management in Bariatric
      Surgery.
AB  - BACKGROUND: The role of preoperative upper-gastrointestinal endoscopy for
      bariatric surgery is still understood only with controversy. The aim of this
      study was to evaluate the prevalence of endoscopic findings and its impact on
      perioperative management. METHODS: Patients who underwent bariatric surgery at
      our center between 2010 and 2013 were systematically analyzed from a prospective
      database. RESULTS: Two hundred and twelve patients with a median body mass index
      of 50 kg/m(2) (range 29-87) underwent 216 bariatric procedures at our center
      between 2010 and 2013. All patients received preoperative upper endoscopy. In 159
      cases (75%), the endoscopy was performed at our center. These cases were included
      in this study. In 37 cases (23%), no abnormal findings were detected. In 122
      cases (76%), upper endoscopy revealed pathologies. No further treatment was
      necessary in 24 cases (15%). Medical treatment was changed in 81 cases (51%). The
      operation was delayed due to medical treatment and re-endoscopy in 13 cases (8%).
      The surgical approach was changed in 4 cases (3%). CONCLUSION: Routinely
      performed preoperative endoscopy before bariatric surgery revealed a high
      prevalence of gastrointestinal diseases with a significant impact on
      perioperative management in two thirds of the cases. Therefore, we recommend
      routine gastroscopy about 2-4 weeks prior to surgery.

PMID- 25997401
TI  - Group A Streptococcus Modulates Host Inflammation by Manipulating
      Polymorphonuclear Leukocyte Cell Death Responses.
AB  - Polymorphonuclear leukocyte (PMN) cell death strongly influences the resolution
      of inflammatory episodes, and may exacerbate adverse pathologies in response to
      infection. We investigated PMN cell death mechanisms following infection by
      virulent group A Streptococcus (GAS). Human PMNs were infected in vitro with a
      clinical, virulent GAS isolate and an avirulent derivative strain, and compared
      for phagocytosis, the production of reactive oxygen species (ROS), mitochondrial
      membrane depolarization and apoptotic markers. C57BL/6J mice were then infected,
      in order to observe the effects on murine PMNs in vivo. Human PMNs phagocytosed
      virulent GAS less efficiently, produced less ROS and underwent reduced
      mitochondrial membrane depolarization compared with phagocytosis of avirulent
      GAS. Morphological and biochemical analyses revealed that PMNs infected with
      avirulent GAS exhibited nuclear fragmentation and caspase-3 activation consistent
      with an anti-inflammatory apoptotic phenotype. Conversely, virulent GAS induced
      PMN vacuolization and plasma membrane permeabilization, leading to a necrotic
      form of cell death. Infection of the mice with virulent GAS engendered
      significantly higher systemic pro-inflammatory cytokine release and localized
      infiltration of murine PMNs, with cells associated with virulent GAS infection
      exhibiting reduced apoptotic potential. Avirulent GAS infection was associated
      with lower levels of proinflammatory cytokines and tissue PMN apoptosis. We
      propose that the differences in PMN cell death mechanisms influence the
      inflammatory responses to infection by GAS. 

PMID- 25997402
TI  - Population Health: Closing Gaps in Care Around the Globe.

PMID- 25997403
TI  - Squash Cytology of a Dural-Based High-Grade Chondrosarcoma May Mimic That of
      Glioblastoma in the Central Nervous System.
AB  - BACKGROUND: Intracranial chondrosarcoma is rare, and most cases occur in the
      skull base. Intradural chondrosarcoma is even rarer. CASE: Here, we describe a
      case of dural chondrosarcoma with a radiation history for nasopharyngeal
      carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years
      earlier, respectively. A 67-year-old man presented with a 3-week memory
      disturbance and dysarthria. Computed tomography and magnetic resonance images of
      the brain revealed a dural-based mass in the left temporal area. Under the
      impression of a glioblastoma, a resection and an intraoperative squash cytology
      were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma
      were characteristic; the nuclei of highly pleomorphic tumor cells were
      hyperchromatic to vesicular with an occasional ground-glass appearance. The
      cytoplasm was of an eosinophilic hyalinized condensed morphology with an
      occasional granular appearance. Histologically, the lobulated mass was composed
      of hypercellular lobules of well-differentiated chondrocytes intermixed with
      anaplastic pleomorphic cells and diagnosed as a conventional grade III
      chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and
      vimentin. Brain invasion was also found. CONCLUSION: Albeit rare, dural-based
      chondrosarcomas should be considered in the differential diagnosis for meningeal
      tumors, especially in the case of previous radiation therapy.

PMID- 25997404
TI  - The Pap Test and Bethesda 2014. "The reports of my demise have been greatly
      exaggerated." (after a quotation from Mark Twain).
AB  - The history of 'The Bethesda System' for reporting cervical cytology goes back
      almost 3 decades. This terminology and the process that created it have had a
      profound impact on the practice of cervical cytology for laboratorians and
      clinicians alike. The Bethesda conferences and their ensuing output have also set
      the stage for standardization of terminology across multiple organ systems,
      including both cytology and histology, have initiated significant research in the
      biology and cost-effective management for human papillomavirus-associated
      anogenital lesions, and, finally, have fostered worldwide unification of clinical
      management for these lesions. Herein, we summarize the process and rationale by
      which updates were made to the terminology in 2014 and outline the contents of
      the new, third edition of the Bethesda atlas and corresponding website.

PMID- 25997405
TI  - Tethered cord syndrome in children: a single-center experience with 162 patients.
AB  - PURPOSE: Tethered cord syndrome (TCS) is not an uncommon clinical problem in
      children. The aim of this retrospective study is to document our experience on
      the surgical treatment of TCS in childhood. METHODS: The data of 162 children who
      underwent surgical treatment for TCS in a 15-year period were reviewed
      retrospectively. Their demographic, clinical, radiological, and surgical features
      were documented. They were divided into two groups as primary and secondary TCS,
      and the surgical technique for each group was demonstrated. Untethering the
      spinal cord and correction of the associated malformation were the standard
      surgical technique for each patient. The results of the treatment were
      summarized. RESULTS: Among the 162 children, 101 (62.3%) of them were female and
      61 were male with a mean age of 62 months. Primary TCS was detected in 43
      patients while secondary TCS was found in 119 (73.4%) patients. Hypertrichosis
      was the most common physical finding while back pain was the common complaint.
      Lipoma, split cord malformation, dermal sinus tract, and myelomeningocele were
      the associated malformations for secondary TCS. CONCLUSIONS: Children should be
      individualized for the treatment of TCS. Each patient must be evaluated
      neurologically and radiologically for the accurate diagnosis. Surgical
      untethering is the safe and effective method of treatment for children with TCS.

PMID- 25997406
TI  - Maternal or zygotic sphingosine kinase is required to regulate zebrafish
      cardiogenesis.
AB  - BACKGROUND: The sphingosine 1-phosphate (S1P) signaling pathway regulates
      zebrafish cardiogenesis, and provides a paradigm for how signaling gradients
      coordinate collective cell migration across tissue layers. It is known that the
      S1P transporter (Spns2) functions in extra-embryonic YSL to activate G protein
      coupled receptor (S1pr2) signaling in endoderm for deposition of positional cues
      (integrin, fibronectin, etc.). Such cues are recognized by overlying lateral
      precardiac mesoderm that migrates to the midline and fuses to form the primordial
      heart tube. However, the source of bio-active S1P is not known. There are
      multiple receptors and it is not known if there are earlier or even receptor
      independent functions for S1P. RESULTS: Because S1P can only be generated by
      sphingosine kinases, we targeted a mutation to the single kinase gene expressed
      during early embryogenesis (sphk2). Zygotic mutants survive to adulthood and
      appear normal, but maternal-zygotic mutant embryos phenocopy null zygotic mutants
      of spns2 or s1pr2. CONCLUSIONS: The data show that maternally derived sphk2 RNA
      is fully sufficient to generate an S1P signaling gradient in the YSL that
      ultimately controls precardiac mesoderm migration during embryogenesis.
      Furthermore, despite maternal expression of sphk2, there are no obvious
      developmental functions requiring its activity prior to stimulation of S1pr2 in
      endoderm.

PMID- 25997407
TI  - Bioinformatics Analysis of Potential Candidates for Therapy of TDRD7 Deficiency
      Induced Congenital Cataract.
AB  - AIMS: The aim of this study was to identify potential candidates and explore the
      possible mechanism in congenital cataract induced by tudor domain-containing 7
      (TDRD7) deficiency. METHODS: The gene expression profile GSE25812 generated from
      18 samples was downloaded from the Gene Expression Omnibus database.
      Differentially expressed genes (DEGs) between disease and normal groups were
      identified. Then, gene ontology and pathway enrichment analysis of DEGs were
      performed. The protein-protein interaction (PPI) network and transcription factor
      (TF) regulatory network were constructed. The modules in the PPI network were
      identified. Significant target genes were selected from the TF regulatory
      network. RESULTS: A total of 329 DEGs were obtained, and downregulated DEGs were
      significantly enriched in biological processes including defense response and
      immune response. In the PPI network, high-degree genes of complement component 1,
      q subcomponent, A/B/C chain (C1QA/C1QB/C1QC), lymphocyte antigen 86 (LY86) and
      neuroblastoma RAS viral oncogene homolog (NRAS) were identified. From the TF
      regulatory network, the heat shock 27 kDa protein 1 (HSPB1) was the target of the
      estrogen receptor 1, and LY86 was the target of the v-myc avian myelocytomatosis
      viral oncogene homolog. CONCLUSION: HSPB1, NRAS, immune response, defense
      response and the related genes LY86, C1QA/C1QB/C1QC may play an important role in
      the development of congenital cataract induced by TDRD7 deficiency. However,
      further experiments are still needed.

PMID- 25997410
TI  - A radical anti-Markovnikov addition of alkyl nitriles to simple alkenes via
      selective sp(3) C-H bond functionalization.
AB  - An efficient hydrocyanoalkylation of unactivated alkenes with alkyl nitriles was
      developed. Through this free-radical-initiated selective activation of the alpha
      C(sp(3))-H bond of acetonitriles, an anti-Markovnikov addition of an alpha-cyano
      C-centered radical to olefins has been achieved, which allows a facile and
      convenient access to functionalized nitriles in large scales. 

PMID- 25997408
TI  - Design and syntheses of hyaluronan oligosaccharide conjugates as inhibitors of
      CD44-Hyaluronan binding.
AB  - Hyaluronan (HA) is an integral component of the extracellular matrix. Its
      interactions with a cell surface receptor CD44 has been shown to play important
      roles in a variety of biological events including cell proliferation and
      metastasis. As multivalent CD44-HA binding is critical for downstream signaling,
      compounds that can selectively disrupt the complex formation of HA polysaccharide
      with CD44 can serve as useful probes of CD44 mediated cellular events as well as
      potential leads for novel therapeutics. Herein, we report the synthesis of
      several series of HA conjugates to target the HA binding pocket of CD44. As a
      small library of HA disaccharide derivatives failed to exhibit any inhibitory
      activities, we focused on HA tetrasaccharide based analogs. Traditional synthetic
      strategies towards HA oligosaccharides involve the construction of backbone from
      the corresponding monosaccharide building blocks, which can be quite tedious. In
      order to expedite the synthesis, we designed a new synthetic route taking
      advantage of the ability of hyaluronidase to generate large quantities of HA
      tetrasaccharide through digestion of HA polysaccharides. The HA tetrasaccharide
      obtained was utilized to prepare multiple S-linked HA analogs bearing aromatic
      groups at the reducing end glycan. One such compound containing an m-benzyl
      phenyl moiety exhibited significant inhibition of CD44-HA binding. Our approach
      provides a new direction towards the design of HA based CD44 antagonists.

PMID- 25997409
TI  - Hereditary protein S deficiency leads to ischemic stroke.
AB  - Hereditary protein S (PS) deficiency is an independent risk factor for venous
      thromboembolism. However, the correlation between PS and arterial thrombotic
      disease, such as cerebral thrombosis, is not clear. The present study focused on
      the molecular mechanisms underlying ischemic stroke caused by a PS gene mutation
      in one family. The activity of antithrombin, protein C and PS in the plasma of
      the proband was measured, and the genes encoding PS were amplified and sequenced.
      The cellular localization and expression of PS were analyzed in HEK-293 cells.
      The proband was a 50-year-old male. Plasma PS activity of the proband was 38.9%,
      which was significantly decreased compared with normal levels. Sequencing
      analysis revealed a PROS1 c.1486_1490delGATTA mutation on exon 12. This
      frameshift mutation converts Asp496 in the precursor PS into the termination
      codon. In addition, the PROS1 mutation was correlated with low PS activity in the
      family. Functional tests revealed that the mutant protein aggregated in the
      cytoplasm and its secretion and expression decreased. In conclusion, protein S
      mutation appeared to be the primary cause of thrombosis in the family of the
      present study. However, the correlation between PS deficiency and ischemic stroke
      requires further investigation.

PMID- 25997411
TI  - Gene set enrichment analysis of pathways and transcription factors associated
      with diabetic retinopathy using a microarray dataset.
AB  - Diabetic retinopathy (DR) is a serious microvascular complication of diabetes,
      which causes visual disability and blindness. Several studies have used gene
      expression profiling of DR to identify the key genes involved in this process;
      however, few studies have focused on the associated pathways and transcription
      factors (TFs), or on the co-expression patterns at the multiple pathways level.
      In this study, we employed a microarray dataset from the public database library
      of the Gene Expression Omnibus (GEO) associated with DR and applied gene set
      enrichment analysis (GSEA) to this dataset and performed candidate TF selection.
      As a result, 10 upregulated pathways, including the type I diabetes mellitus and
      peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as
      59 downregulated pathways, including the ErbB signaling pathway and the mammalian
      target of rapamycin (mTOR) signaling pathway, were identified as DR-related
      pathways. The majority of these pathways have been previously identified, but
      some were novel. Finally, co-expression networks of related pathways were
      constructed using the significant core genes and TFs, such as PPARgamma and
      SMAD4. The results of our study may enhance our understanding of the molecular
      mechanisms associated DR at the genome-wide level.

PMID- 25997413
TI  - Outpatient Treatment of Pneumothorax with a Thoracic Vent: Economic Benefit.
AB  - BACKGROUND: Since rising medical costs currently represent a growing problem
      worldwide, finding cost-effective treatment options is important. In our
      hospital, outpatient treatment of pneumothorax using a thoracic vent began in
      December 2012. OBJECTIVES: We aimed to test our hypothesis that outpatient
      treatment of pneumothorax with a thoracic vent can reduce medical expenses.
      METHODS: Patients were classified into four groups based on treatment: thoracic
      vent with or without surgery or conventional intercostal chest tube drainage with
      or without surgery. We compared mean medical expenses, duration of
      hospitalization and number of physician visits among these four groups. RESULTS:
      During a 2-year period, 65 patients were treated with a thoracic vent (36
      patients) or conventional intercostal chest tube drainage (29 patients). Patients
      treated with a thoracic vent who underwent surgery had a shorter mean duration of
      hospitalization (5.0 +/- 1.3 vs. 10.3 +/- 3.4 days; p < 0.0001) and lower overall
      cost, at JPY 971,830.00 +/- 81,291.80 (USD 10,400.40 +/- 1,464.90) versus JPY
      1,179,791.10 +/- 198,383.10 (USD 13,888.90 +/- 1,965.30; p < 0.0001) compared
      with conventional intercostal chest tube drainage. Nonsurgical patients treated
      with a thoracic vent had lower overall costs, at JPY 79,960.00 +/- 25,643.60 (USD
      890.10 +/- 352.30) versus JPY 268,588.80 +/- 94,636.50 (USD 2,932.80 +/- 903.50;
      p < 0.0001) compared with conventional intercostal chest tube drainage. No
      serious complications were observed. CONCLUSIONS: Outpatient thoracic vent
      treatment can significantly reduce medical expenses and thereby have a major
      economic impact.

PMID- 25997412
TI  - The effects of gestational stress and Selective Serotonin reuptake inhibitor
      antidepressant treatment on structural plasticity in the postpartum brain--A
      translational model for postpartum depression.
AB  - This article is part of a Special Issue "Parental Care". Postpartum depression
      (PPD) is a common complication following childbirth experienced by one in every
      five new mothers. Although the neural basis of PPD remains unknown, previous
      research in rats has shown that gestational stress, a risk factor for PPD,
      induces depressive-like behavior during the postpartum period. Moreover, the
      effect of gestational stress on postpartum mood is accompanied by structural
      modifications within the nucleus accumbens (NAc) and the medial prefrontal cortex
      (mPFC)-limbic regions that have been linked to PPD. Mothers diagnosed with PPD
      are often prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant
      medications and yet little is known about their effects in models of PPD. Thus,
      here we investigated whether postpartum administration of Citalopram, an SSRI
      commonly used to treat PPD, would ameliorate the behavioral and morphological
      consequences of gestational stress. In addition, we examined the effects of
      gestational stress and postpartum administration of Citalopram on structural
      plasticity within the basolateral amygdala (BLA) which together with the mPFC and
      NAc forms a circuit that is sensitive to stress and is involved in mood
      regulation. Our results show that postpartum rats treated with Citalopram do not
      exhibit gestational stress-induced depressive-like behavior in the forced swim
      test. In addition, Citalopram was effective in reversing gestational stress
      induced structural alterations in the postpartum NAc shell and mPFC. We also
      found that gestational stress increased spine density within the postpartum BLA,
      an effect which was not reversed by Citalopram treatment. Overall, these data
      highlight the usefulness of gestational stress as a valid and informative
      translational model for PPD. Furthermore, they suggest that structural
      alterations in the mPFC-NAc pathway may underlie stress-induced depressive-like
      behavior during the postpartum period and provide much needed information on how
      SSRIs may act in the maternal brain to treat PPD. 

PMID- 25997415
TI  - Experiences of People with Diabetes by Payer Type: An Analysis of the Roper
      Diabetes Data Set.
AB  - INTRODUCTION: The study details the experiences of Medicare, Medicaid and
      privately insured patients with diabetes in the United States by focusing on how
      these distinct populations perceive their disease and manage their treatment.
      METHODS: A national survey was fielded among a representative sample of 2,307 US
      adult diagnosed diabetes patients to investigate demographic, lifestyle,
      treatment, access to information, and socioeconomic status. This was achieved
      using a combination of telephone-based interviews and internet-based
      questionnaires administered via KnowledgePanel(r), the only large-scale online
      panel based on a representative random sample of the US population. RESULTS:
      Patients with Medicaid-based insurance face significant differences in diagnosis,
      treatment and intensity of their diabetes as compared to their Medicare and
      privately insured counterparts. Medicaid patients develop diabetes at an earlier
      age with an increased level of severity, and face significant socioeconomic
      concerns. Medicaid patients also have different health information seeking
      preferences than their counterparts, impacted by technology use patterns and
      education preferences. All groups report challenges in paying for their diabetes
      care, though cost-sharing requirements are relatively low. CONCLUSIONS:
      Significant variation in experience between Medicaid, Medicare, and privately
      insured patients can inform disease management and patient engagement strategies.
      Payers, clinicians and public health agencies can leverage these findings to
      design initiatives more effectively and understand how intergroup variability
      impacts program uptake and disease outcomes.

PMID- 25997414
TI  - Granger causal time-dependent source connectivity in the somatosensory network.
AB  - Exploration of transient Granger causal interactions in neural sources of
      electrophysiological activities provides deeper insights into brain information
      processing mechanisms. However, the underlying neural patterns are confounded by
      time-dependent dynamics, non-stationarity and observational noise contamination.
      Here we investigate transient Granger causal interactions using source time
      series of somatosensory evoked magnetoencephalographic (MEG) elicited by air puff
      stimulation of right index finger and recorded using 306-channel MEG from 21
      healthy subjects. A new time-varying connectivity approach, combining
      renormalised partial directed coherence with state space modelling, is employed
      to estimate fast changing information flow among the sources. Source analysis
      confirmed that somatosensory evoked MEG was mainly generated from the
      contralateral primary somatosensory cortex (SI) and bilateral secondary
      somatosensory cortices (SII). Transient Granger causality shows a serial
      processing of somatosensory information, 1) from contralateral SI to
      contralateral SII, 2) from contralateral SI to ipsilateral SII, 3) from
      contralateral SII to contralateral SI, and 4) from contralateral SII to
      ipsilateral SII. These results are consistent with established anatomical
      connectivity between somatosensory regions and previous source modeling results,
      thereby providing empirical validation of the time-varying connectivity analysis.
      We argue that the suggested approach provides novel information regarding
      transient cortical dynamic connectivity, which previous approaches could not
      assess. 

PMID- 25997416
TI  - Sheep production and marketing system in southern Ethiopia: the case of
      Awassazuria district.
AB  - A survey was conducted in Awassazuria district of southern Ethiopia to
      characterize sheep production system. A structured questionnaire was used to
      collect data. Using purposive sampling, a total of 120 households from the
      district were included in the survey. Collected data were analyzed using
      descriptive statistics. Result indicated that Kajima neighbourhood has more
      (p<0.05) grazing land than the others. Communal grazing, roadside grazing, enset
      (false banana, Ensete ventricosum), banana leaf and private grazing land were
      major feed resources for sheep. Lake Awassa and tap water were permanent water
      sources. Watering frequency of sheep varies from once a day to once in 4 days.
      Sheep are primarily kept to generate income and equilibrate benefit and risk and
      for home consumption. The criteria used by the households for purchase and sale
      of sheep are physical characteristics (coat colour, horn and tail) (46.7 %), body
      conformation (35 %), age (10.8 %) and known local ecotype (7.5 %). The reasons of
      slaughter of sheep include festival (55 %), childbirth (18.3 %), wedding (12.5
      %), mutton for home (9 %), circumcision (5 %) and for guest (1.7 %). Farmers
      fatten sheep for New Year (60 %), Easter (30.8 %), Christmas and Arefa (Eid al
      Adha celebration (Feast of the Sacrifice); <10 %). The reasons for expansion of
      sheep flock in the future were market price, high market demand, immediate
      return, ease of management, equilibrium between benefits and risks and
      suitability for home consumption, ranked in decreasing order of importance. The
      sheep production in southern Ethiopia is constrained by shortage of grazing land
      (23.3 %), recurrent drought (17.5 %), disease and parasite (15 %), marketing
      (10.8 %), water shortage (9 %) and other constraints including predators and lack
      of input, capital and lack of extension service. The presence of diversified and
      environmentally adaptable sheep breeds, high demand of mutton in the Awassa town
      and presence of nutritious and unutilized feed resources like fish meal and
      poultry litter were some of the opportunities for sheep production in the area.

PMID- 25997417
TI  - A Rapid Method to Evaluate Cardiac Repolarization Changes: The Effect of Two
      Coffee Strengths on the QT Interval.
AB  - OBJECTIVES: To assess the effect of coffee on ventricular repolarization as
      measured by an electrocardiogram. METHODS: Fifty-four healthy volunteers (34
      males and 20 females, age 23 +/- 5 years) received 1 cup of coffee (caffeine
      content 120 mg) and 11 participants received 2 cups. Blood pressure and heart
      rate were measured prior to coffee and every hour thereafter for 5 h. A 12-lead
      digital Holter recorded continuously, and RR, QT, and QTc intervals were obtained
      every 30 min. RESULTS: Following coffee, RR increased from 802 +/- 102 to 873 +/-
      126 ms (p = 0.001), QT increased from 359 +/- 26 to 367 +/- 27 ms at 1.5 h (p =
      0.047), and QTc decreased from 387 +/- 21 to 381 +/- 23 ms at 30 min (p = 0.001),
      with no changes noted at other time points. Caffeine users and caffeine-naive
      subjects did not differ in QTc effects (p = 0.971). Females had longer QTc at
      each time point than males (p = 0.037), but neither had QTc prolongation
      following coffee. The heart rate decreased from 73 +/- 9 to 69 +/- 11 bpm at 1 h
      (p = 0.018), and no significant changes in blood pressure were noted. The effects
      of 1 or 2 cups of coffee did not differ in terms of QTc (p = 0.663), heart rate
      (p = 0.161), diastolic (p = 0.250), or systolic blood pressure (p = 0.168).
      CONCLUSION: Neither 1 nor 2 cups of coffee increased ventricular repolarization.

PMID- 25997418
TI  - The Combination of 80 Years of Age and Metastatic Castration-Resistant Prostate
      Cancer Remain an Uphill Battle: A Case Report with Cabazitaxel as a Double-Edged
      Sword.
AB  - We report the case of an 80-year-old patient who presented with a progressive
      prostate metastatic cancer with poor performance status. The patient had already
      benefitted from docetaxel and abiraterone. A new line of chemotherapy by
      cabazitaxel was started with good response, and there was a dramatic improvement
      in general status and pain symptoms. Age and performance status alone should not
      be limiting decision factors for elderly cancer patients.

PMID- 25997419
TI  - Inhibition of hTERT/telomerase contributes to the antitumor activity of
      pristimerin in pancreatic ductal adenocarcinoma cells.
AB  - Pristimerin (PM) is a promising anticancer agent that has exhibited strong
      antiproliferative and apoptosis-inducing activity in various types of cancer
      cells. In the present study, we investigated the role of telomerase in mediating
      the antitumor activity of PM in pancreatic ductal adenocarcinoma (PDA) cells. PM
      inhibited cell proliferation, arrested cells in the G1 cell cycle phase and
      induced apoptosis in MiaPaCa-2 and Panc-1 PDA cells. These antitumor activities
      of PM correlated well with the inhibition of human telomerase reverse
      transcriptase (hTERT), the gene that codes for the catalytic subunit of
      telomerase complex. Gene knockin and knockdown approaches demonstrated that hTERT
      regulates the response of PDA cells to PM. PM inhibited hTERT expression by
      suppressing the transcription factors Sp1, c-Myc and NF-kappaB which control
      hTERT gene expression. PM also inhibited protein kinase Akt, which phosphorylates
      and facilitates hTERT nuclear importation and its telomerase activity. These
      findings identified hTERT (telomerase) as a potential therapeutic target of PM
      for the treatment of PDA.

PMID- 25997421
TI  - Stereotactic ablative radiotherapy (SABR) for treatment of central and ultra
      central lung tumors.
AB  - OBJECTIVES: Treatment of central and ultra-central lung tumors with stereotactic
      ablative radiotherapy (SABR) remains controversial due to risks of treatment
      related toxicities compared with peripheral tumors. Here we report our
      institution's experience in treating central and ultra-central lung tumor
      patients with SABR. MATERIALS AND METHODS: We retrospectively reviewed outcomes
      in 68 patients with single lung tumors, 34 central and 34 peripheral, all treated
      with SABR consisting of 50 Gy in 4-5 fractions. Tumor centrality was defined per
      the RTOG 0813 protocol. We defined "ultra-central" tumors as those with GTV
      directly abutting the central airway. RESULTS: Median follow-up time was 18.4
      months and median overall survival was 38.1 months. Two-year overall survival was
      similar between ultra-central, central, and peripheral NSCLC (80.0% vs. 63.2% vs.
      86.6%, P=0.62), as was 2-year local failure (0% vs. 10.0% vs. 16.3%, P=0.64).
      Toxicity rates were low and comparable between the three groups, with only two
      cases of grade 3 toxicity (chest wall pain), and one case of grade 4 toxicity
      (pneumonitis) observed. Patients with ultra-central tumors experienced no
      symptomatic toxicities over a median follow-up time of 23.6 months. Dosimetric
      analysis revealed that RTOG 0813 central airway dose constraints were frequently
      not achieved in central tumor treatment plans, but this did not correlate with
      increased toxicity rate. CONCLUSION: Patients with central and ultra-central lung
      tumors treated with SABR (50 Gy in 4-5 fractions) experienced few toxicities and
      good outcomes, similar to patients with peripheral lung tumors.

PMID- 25997420
TI  - Vascular Parkinsonism: deconstructing a syndrome.
AB  - Progressive ambulatory impairment and abnormal white matter (WM) signal on
      neuroimaging come together under the diagnostic umbrella of vascular parkinsonism
      (VaP). A critical appraisal of the literature, however, suggests that (1) no
      abnormal structural imaging pattern is specific to VaP; (2) there is poor
      correlation between brain MRI hyperintensities and microangiopathic brain disease
      and parkinsonism from available clinicopathologic data; (3) pure parkinsonism
      from vascular injury ("definite" vascular parkinsonism) consistently results from
      ischemic or hemorrhagic strokes involving the SN and/or nigrostriatal pathway,
      but sparing the striatum itself, the cortex, and the intervening WM; and (4) many
      cases reported as VaP may represent pseudovascular parkinsonism (e.g.,
      Parkinson's disease or another neurodegenerative parkinsonism, such as PSP with
      nonspecific neuroimaging signal abnormalities), vascular pseudoparkinsonism
      (e.g., akinetic mutism resulting from bilateral mesial frontal strokes or
      apathetic depression from bilateral striatal lacunar strokes), or pseudovascular
      pseudoparkinsonism (e.g., higher-level gait disorders, including normal-pressure
      hydrocephalus with transependimal exudate). These syndromic designations are
      preferable over VaP until pathology or validated biomarkers confirm the
      underlying nature and relevance of the leukoaraiosis. (c) 2015 International
      Parkinson and Movement Disorder Society. 

PMID- 25997422
TI  - Prophylactic cranial irradiation (PCI). Still a no-brainer?
AB  - Although prophylactic cranial irradiation (PCI) has been the standard of practice
      for patients successfully treated for limited stage small cell lung cancer for
      decades, subsequent changes in patient selection, updated brain imaging
      guidelines, an increased understanding of the mechanisms underlying the
      deleterious effects of whole brain irradiation as well as ongoing investigations
      into improving radiation treatment delivery have begun to question the current
      role of PCI. Who should be treated and how? This review attempts to gather
      together evidence for improving patient selection and describe potential
      improvements in treatment delivery. 

PMID- 25997423
TI  - Gold and silver catalysis: from organic transformation to bioconjugation.
AB  - This review focuses on gold (including gold(I) and gold(III) complexes, and gold
      nanoparticles) and silver(I) catalysis, including aerobic oxidation, activation
      of C-H bonds and activation of C-C multiple bonds, and their applications in the
      modification of biomolecules, including oligosaccharides, peptides and
      polypeptides, reported since the year 2000. Because of the high carbophilicity of
      gold and silver compounds, gold or silver-catalysed/mediated organic
      transformations feature high functional group tolerance, excellent regio-,
      diastereo- or enantioselectivity and/or high product turnover numbers under mild
      reaction conditions.

PMID- 25997424
TI  - Agency, access, and Anopheles: neighborhood health perceptions and the
      implications for community health interventions in Accra, Ghana.
AB  - BACKGROUND: Social and environmental factors are increasingly recognized for
      their ability to influence health outcomes at both individual and neighborhood
      scales in the developing urban world. Yet issues of spatial heterogeneity in
      these complex environments may obscure unique elements of neighborhood life that
      may be protective or harmful to human health. Resident perceptions of
      neighborhood effects on health may help to fill gaps in our interpretation of
      household survey results and better inform how to plan and execute neighborhood
      level health interventions. OBJECTIVE: We evaluate differences in housing and
      socioeconomic indicators and health, environment, and neighborhood perceptions
      derived from the analysis of a household survey and a series of focus groups in
      Accra, Ghana. We then explore how neighborhood perceptions can inform survey
      results and ultimately neighborhood-level health interventions. DESIGN: Eleven
      focus groups were conducted across a socioeconomically stratified sample of
      neighborhoods in Accra, Ghana. General inductive themes from the focus groups
      were analyzed in tandem with data collected in a 2009 household survey of 2,814
      women. In-depth vignettes expand upon the three most salient emergent themes.
      RESULTS: Household and socioeconomic characteristics derived from the focus
      groups corroborated findings from the survey data. Focus group and survey results
      diverged for three complex health issues: malaria, health-care access, and sense
      of personal agency in promoting good health. CONCLUSION: Three vignettes
      reflecting community views about malaria, health-care access, and sense of
      personal agency in promoting good health highlight the challenges facing
      community health interventions in Accra and exemplify how qualitatively derived
      neighborhood-level health effects can help shape health interventions.

PMID- 25997426
TI  - [Prediction of coronary artery stenosis by measurement of total plaque area and
      thickness versus intima media thickness of the carotid artery].
AB  - Total plaque area (TPA), maximum plaque thickness and intima media thickness
      (IMT) in the carotid arteries of 431 patients aged 27-88 years were measured 1
      day before a planned coronary artery angiography without any clinical knowledge
      about the patient. Age-related cut-off values of the TPA for the presence of
      coronary stenosis were evaluated. Using ultrasound four types of carotid artery
      atherosclerosis were identified. The accuracy of detection of cardiovascular
      coronary stenosis was 87% for types III and IVb. No type I patient had coronary
      stenosis. The IMT was significantly less predictive: the area under the curve
      (AUC) for TPA by age and plaque thickness was 0.82 (95% CI: 0.78-0.85) versus IMT
      0.59 (95% CI: 0.54-0.64, p = 0.001). Prediction with TPA measurement by age and
      plaque thickness was better than TPA alone: AUC 0.82 (95% CI: 0.78-0.85) versus
      0.77 (95% CI: 0.73-0.81, p = 0.0028), respectively. In a second cohort of 2566
      healthy men and 1216 healthy women aged between 20 and 64 years who were examined
      in an occupational screening program, 11.2% of the men and 3.4% of the women
      showed a type III or IVb result. In the mean follow-up of period of 23.4 +/- 14.4
      months, 14 heart attacks, 7 bypass operations and 3 stent implantations occurred
      and 6 subjects showed coronary stenosis between 50% and 95% in coronary
      angiography. In the baseline examination 26 out of 30 patients showed a type III
      or IVb result. In the case of men and women with types III and IVb diagnosis by
      ultrasound, pharmaceutical treatment could be indicated in order to reduce the
      risk of cardiovascular events. Type I patients do not need preventive medication
      or coronary catheterization.

PMID- 25997425
TI  - Serum NT-proBNP on admission can predict ST-segment resolution in patients with
      acute myocardial infarction after primary percutaneous coronary intervention.
AB  - OBJECTIVE: The aim of this study was to investigate the value of initial serum N
      terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in ST-segment
      elevation myocardial infarction (STEMI) patients for predicting ST-segment
      resolution (STR) after primary percutaneous coronary intervention (pPCI).
      PATIENTS AND METHODS: Consecutive STEMI patients (n = 218) who underwent pPCI
      were assigned to an STR group (>= 50 % resolution) or a non-STR group (< 50 %
      resolution). All patients were followed up for 12 months, and major adverse
      cardiac events were recorded. Data related to the pPCI procedure, biochemical
      parameters, and cardiac markers were compared between the two groups. Predictive
      factors of non-STR were also identified. RESULTS: STR at 180 min after pPCI
      occurred in 202 patients (92.7 %). Compared to the STR group, patients in the non
      STR group had a significantly lower left ventricular ejection fraction, a larger
      left ventricular end-diastolic dimension, and significantly higher serum
      concentrations of glycosylated hemoglobin and NT-proBNP. Multivariate logistic
      regression analysis indicated that a high serum NT-proBNP level in STEMI patients
      on hospital admission was the only independent predictive factor of non-STR after
      pPCI. An NT-proBNP concentration of >= 2,563.6 pg/ml had a sensitivity of 81.2 %
      and a specificity of 65.8 %. CONCLUSIONS: Serum NT-proBNP concentrations in STEMI
      patients on hospital admission were useful in predicting non-STR after pPCI.

PMID- 25997427
TI  - mRNA-transfected Dendritic Cells Expressing Polypeptides That Link MHC-I
      Presentation to Constitutive TLR4 Activation Confer Tumor Immunity.
AB  - Recently, we have developed a novel genetic platform for improving dendritic cell
      (DC) induction of peptide-specific CD8 T cells, based on membrane-anchored beta2
      microglobulin (beta2m) linked to a selected antigenic peptide at its N-terminus
      and to the cytosolic domain of toll-like receptor (TLR)4 C-terminally. In vitro
      transcribed mRNA transfection of antigen presenting cells resulted in
      polypeptides that efficiently coupled peptide presentation to cellular
      activation. In the present study, we evaluated the immunogenicity of such
      constructs in mRNA-transfected immature murine bone marrow-derived DCs. We show
      that the encoded peptide beta2m-TLR4 products were expressed at the cell surface
      up to 72 hours and stimulated the maturation of DCs. In vivo, these DCs prompted
      efficient peptide-specific T-cell activation and target cell killing which were
      superior to those induced by peptide-loaded, LPS-stimulated DCs. This superiority
      was also evident in the ability to protect mice from tumor progression following
      the administration of B16F10.9 melanoma cells and to inhibit the development of
      pre-established B16F10.9 tumors. Our results provide evidence that the products
      of two recombinant genes encoding for peptide-hbeta2m-TLR4 and peptide-hbeta2m
      K(b) expressed from exogenous mRNA can cooperate to couple Major
      Histocompatibility Complex (MHC-I) peptide presentation to TLR-mediated
      signaling, offering a safe, economical and highly versatile genetic platform for
      a novel category of CTL-inducing vaccines. 

PMID- 25997428
TI  - ACE2 Therapy Using Adeno-associated Viral Vector Inhibits Liver Fibrosis in Mice.
AB  - Angiotensin converting enzyme 2 (ACE2) which breaks down profibrotic peptide
      angiotensin II to antifibrotic peptide angiotensin-(1-7) is a potential
      therapeutic target in liver fibrosis. We therefore investigated the long-term
      therapeutic effect of recombinant ACE2 using a liver-specific adeno-associated
      viral genome 2 serotype 8 vector (rAAV2/8-ACE2) with a liver-specific promoter in
      three murine models of chronic liver disease, including carbon tetrachloride
      induced toxic injury, bile duct ligation-induced cholestatic injury, and
      methionine- and choline-deficient diet-induced steatotic injury. A single
      injection of rAAV2/8-ACE2 was administered after liver disease has established.
      Hepatic fibrosis, gene and protein expression, and the mechanisms that rAAV2/8
      ACE2 therapy associated reduction in liver fibrosis were analyzed. Compared with
      control group, rAAV2/8-ACE2 therapy produced rapid and sustained upregulation of
      hepatic ACE2, resulting in a profound reduction in fibrosis and profibrotic
      markers in all diseased models. These changes were accompanied by reduction in
      hepatic angiotensin II levels with concomitant increases in hepatic angiotensin
      (1-7) levels, resulting in significant reductions of NADPH oxidase assembly,
      oxidative stress and ERK1/2 and p38 phosphorylation. Moreover, rAAV2/8-ACE2
      therapy normalized increased intrahepatic vascular tone in fibrotic livers. We
      conclude that rAAV2/8-ACE2 is an effective liver-targeted, long-term therapy for
      liver fibrosis and its complications without producing unwanted systemic effects.

PMID- 25997429
TI  - How can we strengthen students' social relations in order to reduce school
      dropout? An intervention development study within four Danish vocational schools.
AB  - BACKGROUND: This article describes the rationale and contents of an intervention
      program aimed at strengthening students' social relations in order to reduce
      dropout from vocational schools in Denmark. Taking its theoretical cue from the
      concept of 'social participation', a qualitative study was performed to
      investigate the specific relationships between the social environment within the
      schools and the institutional structures in order to analyse reasons for school
      dropout and their relation to well-being, cigarette smoking and substance use.
      METHODS: The development study was based on ethnographic methods, including 22
      qualitative interviews with students 17-19 years old and fieldwork with
      participant observations at four vocational schools over 40 days, including
      informal interviews and discussion meetings with managers, teachers, counselors
      and students. As part of the fieldwork, four additional qualitative interviews
      and four group interviews were conducted with students 16-25 years old. RESULTS:
      The qualitative data collection resulted in seven major themes to be addressed in
      the intervention: social relations, sole focus on professional skills,
      institutionalized individualization, importance of the introduction period,
      physical surroundings and schedules, tobacco and cannabis use and communication
      about drug use. The program addressing these themes incorporates suggestions that
      are meant to improve how teachers welcome new students, to enable greater
      integration of social and educational activities and to enhance the capacity of
      teachers and counselors to deal with drug use problems among students.
      CONCLUSION: The development of new intervention programs might benefit from
      adopting a theoretical and methodological perspective that enables a closer
      exploration of the everyday social practices in which interventions are embedded.
      Thus, we aimed to create a comprehensive intervention that worked through
      organizational changes in everyday school practices. Intervention programs must
      be planned in dialogue and collaboration with practitioners in the field to
      ensure the pertinence and usability of the program.

PMID- 25997431
TI  - Doctors facing manslaughter charges should not automatically be suspended, High
      Court rules.

PMID- 25997430
TI  - Assessing health-care providers' readiness for reporting quality and patient
      safety indicators at primary health-care centres in Lebanon: a national cross
      sectional survey.
AB  - BACKGROUND: Successful endorsement of quality indicators hinges on the readiness
      and acceptability of care providers for those measures. This paper aims to assess
      the readiness of care providers in the primary health-care sector in Lebanon for
      the implementation of quality and patient safety indicators. METHODS: A cross
      sectional survey methodology was utilized to gather information from 943 clinical
      care providers working at 123 primary health-care centres in Lebanon. The
      questionnaire included two sections: the first assessed four readiness dimensions
      (appropriateness, management support, efficacy, and personal valence) of clinical
      providers to use quality and safety indicators using the Readiness for
      Organization Change (ROC) scale, and the second section assessed the safety
      attitude at the primary care centre utilizing the Agency of Health Research and
      Quality (AHRQ) Safety Attitude Questionnaire (SAQ)-Ambulatory version. RESULTS:
      Although two thirds (66%) of respondents indicated readiness for implementation
      of quality and patient safety indicators in their centres, there appear to be
      differences by professional group. Physicians displayed the lowest scores on all
      readiness dimensions except for personal valence which was the lowest among
      nurses (60%). In contrast, allied health professionals displayed the highest
      scores across all readiness dimensions. Generally, respondents reflected a
      positive safety attitude climate in the centres. Yet, there remain a few areas of
      concern related to punitive culture (only 12.8% agree that staff should not be
      punished for reported errors/incidents), continuity of care (41.1% believe in the
      negative consequences of lack in continuity of care process), and resources
      (48.1% believe that the medical equipment they have are adequate). Providers with
      the highest SAQ score had 2.7, 1.7, 7 and 2.4 times the odds to report a higher
      readiness on the appropriateness, efficacy, management and personal valence ROC
      subscales, respectively (P value <0.01). Nurses displayed relatively lower odds
      of readiness across all other ROC subscales as compared to all other providers.
      CONCLUSION: Health-care providers at the primary health care (PHC) centres in
      Lebanon are ready to engage in employing quality and patient safety indicators.
      This is a key finding given the active efforts by the MoPH to strengthen the
      quality culture in the PHC sector through various strategies.

PMID- 25997432
TI  - Intra-population level variation in thresholds for physical dormancy-breaking
      temperature.
AB  - BACKGROUND AND AIMS: Intra-population variation in seed dormancy is an advantage
      for population persistence in unpredictable environments. The important role
      played by physically dormant species in these habitats makes understanding the
      level of variation in their dormancy a key ecological question. Heat produced in
      the soil is the major dormancy-breaking stimulus and, in fire prone ecosystems,
      soil temperatures generated by fire may vary spatially and over time. While many
      studies have investigated variation in initial dormancy, a measure that is of
      little value in fire-prone ecosystems, where initial dormancy levels are
      uniformly high, intra-population variation in dormancy-breaking temperature
      thresholds has never been quantified. This study predicted that species would
      display variation in dormancy-breaking temperature thresholds within populations,
      and investigated whether this variation occurred between individual plants from
      the same maternal environment. METHODS: The intra-population variation in
      dormancy-breaking thresholds of five common physically dormant shrub species
      (family Fabaceae) from fire-prone vegetation in south-eastern Australia was
      assessed using heat treatments and germination trials. Replicate batches of seeds
      from each of four maternal plants of Dillwynia floribunda, Viminaria juncea,
      Bossiaea heterophylla, Aotus ericoides and Acacia linifolia were treated at 40,
      60, 80, 100 and 120  degrees C. KEY RESULTS: Dormancy-breaking response to heat
      treatments varied significantly among individual plants for all species, with
      some individuals able to germinate after heating at low temperatures and others
      restricting germination to temperatures that only occur as a result of high
      severity fires. Germination rate (T50) varied among individuals of three species.
      CONCLUSIONS: Variation detected among individuals that were in close proximity to
      each other indicates that strong differences in dormancy-breaking temperature
      thresholds occur throughout the broader population. Differences found at the
      individual plant level could contribute to subsequent variation within the seed
      bank, providing a bet-hedging strategy, and represent a mechanism for increasing
      the probability of population persistence in the face of fire regime variability.

PMID- 25997433
TI  - The utility of ultrasound-guided thoracentesis and pleural biopsy in undiagnosed
      pleural exudates.
AB  - We assessed the utility of ultrasound to guide the selection of closed pleural
      biopsy technique and site and to assess the respective contributions of repeat
      thoracentesis and closed pleural biopsy in 100 consecutive patients with
      undiagnosed pleural exudates. Thoracentesis was more likely to be diagnostic in
      TB than malignancy (77.8% vs 31.0%, p<0.001). The addition of ultrasound-guided
      biopsy increased the combined yield for all diagnoses from 48.0% to 90.0%
      (p<0.001), for malignancy from 31.0% to 89.7% (p<0.001) and for TB from 77.8% to
      88.9% (p=0.688). Our findings suggest that this minimally invasive approach has a
      high diagnostic yield. 

PMID- 25997434
TI  - Derivation and Cross-Validation of Cutoff Scores for Patients With Schizophrenia
      Spectrum Disorders on WAIS-IV Digit Span-Based Performance Validity Measures.
AB  - Two studies were conducted to identify and cross-validate cutoff scores on the
      Wechsler Adult Intelligence Scale-Fourth Edition Digit Span-based embedded
      performance validity (PV) measures for individuals with schizophrenia spectrum
      disorders. In Study 1, normative scores were identified on Digit Span-embedded PV
      measures among a sample of patients (n = 84) with schizophrenia spectrum
      diagnoses who had no known incentive to perform poorly and who put forth valid
      effort on external PV tests. Previously identified cutoff scores resulted in
      unacceptable false positive rates and lower cutoff scores were adopted to
      maintain specificity levels >=90%. In Study 2, the revised cutoff scores were
      cross-validated within a sample of schizophrenia spectrum patients (n = 96)
      committed as incompetent to stand trial. Performance on Digit Span PV measures
      was significantly related to Full Scale IQ in both studies, indicating the need
      to consider the intellectual functioning of examinees with psychotic spectrum
      disorders when interpreting scores on Digit Span PV measures.

PMID- 25997435
TI  - Urinary cadmium and mortality from all causes, cancer and cardiovascular disease
      in the general population: systematic review and meta-analysis of cohort studies.
AB  - BACKGROUND: Cadmium is a toxic heavy metal distributed in the environment. We
      conducted a systematic review and meta-analysis to examine the association
      between urinary cadmium concentration and mortality from all causes, cancer and
      cardiovascular disease (CVD) in the general population. METHODS: Studies were
      identified by searching PubMed and Embase (to 30 March 2015) and the reference
      lists of retrieved articles. We included prospective studies that reported hazard
      ratios (HR) with 95% confidence intervals (CI) for the association between
      urinary cadmium concentration and all-cause, cancer or CVD mortality. A random
      effects model was used to combine study-specific results. RESULTS: Nine cohort
      studies, including 5600 deaths from all causes, 1332 deaths from cancer and 1715
      deaths from CVD, were eligible for inclusion in the meta-analysis. The overall
      HRs for the highest vs lowest category of urinary cadmium were1.44 (95% CI, 1.25
      1.64; I(2 )= 40.5%) for all-cause mortality (six studies), 1.39 (95% CI, 0.96
      1.99; I(2 )= 75.9%) for cancer mortality (four studies) and 1.57 (95% CI, 1.27
      1.95; I(2 )= 34.0%) for CVD mortality (five studies). In an analysis restricted
      to six cohort studies conducted in populations with a mean urinary cadmium
      concentration of <=1 ug/g creatinine, the HRs were 1.38 (95% CI, 1.17-1.63; I(2
      )= 48.3%) for all-cause mortality, 1.56 (95% CI, 0.98-2.47; I(2 )= 81.0%) for
      cancer mortality and 1.50 (95% CI, 1.18-1.91; I(2 )= 38.2%) for CVD mortality.
      CONCLUSIONS: Even at low-level exposure, cadmium appears to be associated with
      increased mortality. Further large prospective studies of cadmium exposure and
      mortality are warranted.

PMID- 25997438
TI  - Potent anti-obesity effect of enteric-coated lactoferrin: decrease in visceral
      fat accumulation in Japanese men and women with abdominal obesity after 8-week
      administration of enteric-coated lactoferrin tablets - CORRIGENDUM.

PMID- 25997437
TI  - Review: Dietary fiber utilization and its effects on physiological functions and
      gut health of swine.
AB  - Although dietary fiber (DF) negatively affects energy and nutrient digestibility,
      there is growing interest for the inclusion of its fermentable fraction in pig
      diets due to their functional properties and potential health benefits beyond
      supplying energy to the animals. This paper reviews some of the relevant
      information available on the role of different types of DF on digestion of
      nutrients in different sections of the gut, the fermentation process and its
      influence on gut environment, especially production and utilization of
      metabolites, microbial community and gut health of swine. Focus has been given on
      DF from feed ingredients (grains and coproducts) commonly used in pig diets. Some
      information on the role DF in purified form in comparison with DF in whole matrix
      of feed ingredients is also presented. First, composition and fractions of DF in
      different feed ingredients are briefly reviewed. Then, roles of different
      fractions of DF on digestion characteristics and physiological functions in the
      gastrointestinal tract (GIT) are presented. Specific roles of different fractions
      of DF on fermentation characteristics and their effects on production and
      utilization of metabolites in the GIT have been discussed. In addition, roles of
      DF fermentation on metabolic activity and microbial community in the intestine
      and their effects on intestinal health are reviewed and discussed. Evidence
      presented in this review indicates that there is wide variation in the
      composition and content of DF among feed ingredients, thereby their physico
      chemical properties in the GIT of swine. These variations, in turn, affect the
      digestion and fermentation characteristics in the GIT of swine. Digestibility of
      DF from different feed ingredients is more variable and lower than that of other
      nutrients like starch, sugars, fat and CP. Soluble fractions of DF are fermented
      faster, produce higher amounts of volatile fatty acid than insoluble fractions,
      and favors growth of beneficial microbiota. Thus, selective inclusion of DF in
      diets can be used as a nutritional strategy to optimize the intestinal health of
      pigs, despite its lower digestibility and consequential negative effect on
      digestibility of other nutrients. 

PMID- 25997439
TI  - Increase in osteoclastogenesis in an obese Otsuka Long-Evans Tokushima fatty rat
      model.
AB  - In the present study, the effects of obesity on bone metabolism were investigated
      using a hyperphagic and obese rat model, the Otsuka Long-Evans Tokushima fatty
      (OLETF) rat, which exhibits normal glycemic control at 8 weeks of age. Body
      weight, food intake, fat mass, markers of bone resorption, the activities of
      tartrate-resistant acid phosphatase (TRAP) and cathepsin K, the number of
      osteoclasts in the proximal tibia, and the serum C-terminal crosslinking
      telopeptide level were higher in OLETF rats than those in control rats (Long
      Evans Tokushima Otsuka; LETO). However, no differences in markers of bone
      formation, alkaline phosphatase activity, the number of osteoblasts in the
      proximal tibia or the serum osteocalcin level were observed. mRNA and protein
      levels of c-fms, receptor for activation of nuclear factor-kappaB (RANK), RANK
      ligand (RANKL), TRAP and cathepsin K were significantly increased in OLETF rats,
      although those levels of macrophage colony-stimulating factor (M-CSF) and
      osteoprotegerin (OPG) were similar to those in LETO rats. The level of serum
      tumor necrosis factor alpha (TNFalpha), and that of TNFalpha mRNA in bone,
      increased in association with the activation of NFkappaB. Furthermore, a
      frequency analysis and a colony formation assay respectively showed that the
      number of osteoclast precursors and the number of colony-forming cells induced by
      M-CSF each increased in OLETF rats compared with the control group. These results
      suggested that hyperphagia-induced obesity with normal glycemic control induces
      the upregulation of osteoclastogenesis that is associated with an increase in the
      expression of c-fms, RANK and RANKL, which is induced by TNFalpha, via the
      activation of NFkappaB.

PMID- 25997436
TI  - Mendelian randomization study of height and risk of colorectal cancer.
AB  - BACKGROUND: For men and women, taller height is associated with increased risk of
      all cancers combined. For colorectal cancer (CRC), it is unclear whether the
      differential association of height by sex is real or is due to confounding or
      bias inherent in observational studies. We performed a Mendelian randomization
      study to examine the association between height and CRC risk. METHODS: To
      minimize confounding and bias, we derived a weighted genetic risk score
      predicting height (using 696 genetic variants associated with height) in 10,226
      CRC cases and 10,286 controls. Logistic regression was used to estimate odds
      ratios (OR) and 95% confidence intervals (95% CI) for associations between
      height, genetically predicted height and CRC. RESULTS: Using conventional
      methods, increased height (per 10-cm increment) was associated with increased CRC
      risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was
      associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men
      (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater
      numbers of (weighted) height-increasing alleles (per 1-unit increase) was
      associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI =
      1.01-1.14) and for women (OR = 1.09, 95% CI =  .01-1.19). There was weaker
      evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). CONCLUSION:
      We provide evidence for a causal association between height and CRC for women.
      The CRC-height association for men remains unclear and warrants further
      investigation in other large studies.

PMID- 25997440
TI  - The presence of primary cilia in cancer cells does not predict responsiveness to
      modulation of smoothened activity.
AB  - Primary cilia are microtubule-based organelles that regulate smoothened-dependent
      activation of the GLI transcription factors in canonical hedgehog signaling. In
      many cancers, primary cilia are markedly decreased or absent. The lack of primary
      cilia may inhibit or alter canonical hedgehog signaling and, thereby, interfere
      in the cellular responsiveness to modulators of smoothened activity. Clinical
      trials of smoothened antagonists for cancer treatment have shown the best
      response in basal cell carcinomas, with limited response in other solid tumors.
      To determine whether the presence or absence of primary cilia in cancer cells
      will predict their responsiveness to modulation of smoothened activity, we
      compared the ability of an agonist and/or inhibitor of smoothened (SAG and SANT1,
      respectively) to modulate GLI-mediated transcription, as measured by GLI1 mRNA
      level or GLI-luciferase reporter activity, in non-cancer cells with primary cilia
      (ovarian surface epithelial cells and breast fibroblasts), in cancer cells that
      cannot assemble primary cilia (MCF7, MDA-MB-231 cell lines), and in cancer cells
      with primary cilia (SKOV3, PANC1 cell lines). As expected, SAG and SANT1 resulted
      in appropriate modulation of GLI transcriptional activity in ciliated non-cancer
      cells, and failed to modulate GLI transcriptional activity in cancer cells
      without primary cilia. However, there was also no modulation of GLI
      transcriptional activity in either ciliated cancer cell line. SAG treatment of
      SKOV3 induced localization of smoothened to primary cilia, as assessed by
      immunofluorescence, even though there was no increase in GLI transcriptional
      activity, suggesting a defect in activation of SMO in the primary cilia or in
      steps later in the hedgehog pathway. In contrast to SKOV3, SAG treatment of PANC1
      did not cause the localization of smoothened to primary cilia. Our data
      demonstrate that the presence of primary cilia in the cancer epithelial cells
      lines tested does not indicate their responsiveness to smoothened activation or
      inhibition. 

PMID- 25997441
TI  - Identification of genes associated with laryngeal squamous cell carcinoma samples
      based on bioinformatic analysis.
AB  - The present study aimed to investigate the differentially expressed genes (DEGs)
      between laryngeal squamous cell carcinoma (LSCC) samples and non-neoplastic
      laryngeal squamous cell samples, and the underlying biological mechanism. Gene
      expression profile data of GSE51985 and GSE10288 were obtained from the Gene
      Expression Omnibus database. The DEGs between the LSCC and normal samples were
      identified using the rowtest function in the genefilter package. Hierarchical
      clustering for DEGs was performed to confirm the distinction between the
      identified DEGs, and Gene Ontology term and pathway enrichment analyses were
      performed to determine the underlying function of the DEGs. In addition, protein
      protein interaction networks were established to investigate the interactive
      mechanism of the DEGs. A total of 1,288 upregulated genes and 317 downregulated
      genes were identified between the LSCC samples and non-neoplastic LSC samples in
      the GSE51985 dataset, and five upregulated and 26 downregulated genes were
      identified in the samples from the GSE10288 dataset. The DEGs were clearly
      distinguished between the LSCC sample and the non-neoplastic LSCC sample by
      hierarchical clustering. The upregulated genes were predominantly involved in the
      cell cycle, cell division or focal adhesion, and the 295 upregulated genes formed
      374 protein interaction pairs in interaction network analysis. The results
      revealed that the genes involved in the cell cycle, in cell division or in focal
      adhesion were associated with the development and progression of LSCC.

PMID- 25997442
TI  - Impact of 6-month earlier versus postponed initiation of rotigotine on long-term
      outcome: post hoc analysis of patients with early Parkinson's disease with mild
      symptom severity.
AB  - OBJECTIVE: Investigate impact of 6-month earlier versus postponed initiation of
      rotigotine in patients with early Parkinson's disease (PD) with mild symptom
      severity. BACKGROUND: Long-term benefit of rotigotine in early-PD has been
      demonstrated: SP702 (NCT00594165) and SP716 (NCT00599196) were long-term, open
      label extensions of double-blind, placebo-controlled studies of 6-month
      maintenance; rotigotine was well tolerated for up to 6 years, and demonstrated
      efficacy (Unified Parkinson's Disease Rating Scale [UPDRS] II + III below
      baseline) for ~ 2 years (SP702) and ~ 4 years (SP716). METHODS: Post hoc analysis
      of patients at Hoehn and Yahr 1-2; groups defined by treatment received in 6
      month double-blind studies: 'Rotigotine-Rotigotine' received rotigotine (n =
      221), 'Placebo-Rotigotine' received placebo (n = 125). RESULTS: At the start of
      open-label rotigotine maintenance, UPDRS II + III mean +/- SD change from double
      blind baseline was: -8.5 +/- 10.6 'Rotigotine-Rotigotine', -7.7 +/- 9.0 'Placebo
      Rotigotine.' After this initial improvement scores gradually increased: It took ~
      45 months for mean scores to cross baseline in 'Rotigotine-Rotigotine', and ~ 21
      months in 'Placebo-Rotigotine.' At the time mean UPDRS II + III had crossed
      baseline in 'Placebo-Rotigotine' (open-label week 84; ~ 21 months), treatment
      difference (LS-mean) to 'Rotigotine-Rotigotine' change from baseline was -3.89
      (95% CI -6.94, -0.84); p = 0.013. CONCLUSIONS: In this post hoc analysis, 6-month
      earlier initiation of rotigotine resulted in slower return to baseline mean UPDRS
      II + III; initiation of rotigotine in patients with minimal/no functional
      disability or impairment may lead to an extended benefit.

PMID- 25997443
TI  - Controlling the interplay between Agrobacterium tumefaciens and plants during the
      transient expression of proteins.
AB  - In May 2012, the first plant-derived biopharmaceutical protein received full
      regulatory approval for therapeutic use in humans. Although plant-based
      expression systems have many advantages, they can suffer from low expression
      levels and, depending on the species, the presence of potentially toxic secondary
      metabolites. Transient expression mediated by Agrobacterium tumefaciens can be
      used to increase product yields but may also increase the concentration of
      secondary metabolites generated by plant defense responses. We have recently
      investigated the sequence of defense responses triggered by A. tumefaciens in
      tobacco plants and considered how these can be modulated by the transient
      expression of type III effectors from Pseudomonas syringae. Here we discuss the
      limitations of this approach, potential solutions and additional issues
      concerning transient expression in plants that should be investigated in greater
      detail. 

PMID- 25997444
TI  - Stressed hearts inflame the body (in a good way).

PMID- 25997445
TI  - Calcium sensor kinase activates potassium uptake systems in gland cells of Venus
      flytraps.
AB  - The Darwin plant Dionaea muscipula is able to grow on mineral-poor soil, because
      it gains essential nutrients from captured animal prey. Given that no nutrients
      remain in the trap when it opens after the consumption of an animal meal, we here
      asked the question of how Dionaea sequesters prey-derived potassium. We show that
      prey capture triggers expression of a K(+) uptake system in the Venus flytrap. In
      search of K(+) transporters endowed with adequate properties for this role, we
      screened a Dionaea expressed sequence tag (EST) database and identified DmKT1 and
      DmHAK5 as candidates. On insect and touch hormone stimulation, the number of
      transcripts of these transporters increased in flytraps. After cRNA injection of
      K(+)-transporter genes into Xenopus oocytes, however, both putative K(+)
      transporters remained silent. Assuming that calcium sensor kinases are regulating
      Arabidopsis K(+) transporter 1 (AKT1), we coexpressed the putative K(+)
      transporters with a large set of kinases and identified the CBL9-CIPK23 pair as
      the major activating complex for both transporters in Dionaea K(+) uptake. DmKT1
      was found to be a K(+)-selective channel of voltage-dependent high capacity and
      low affinity, whereas DmHAK5 was identified as the first, to our knowledge,
      proton-driven, high-affinity potassium transporter with weak selectivity. When
      the Venus flytrap is processing its prey, the gland cell membrane potential is
      maintained around -120 mV, and the apoplast is acidified to pH 3. These
      conditions in the green stomach formed by the closed flytrap allow DmKT1 and
      DmHAK5 to acquire prey-derived K(+), reducing its concentration from millimolar
      levels down to trace levels. 

PMID- 25997446
TI  - Reply to Garcia et al.: Common mistakes in measuring frequency-dependent word
      characteristics.

PMID- 25997447
TI  - The language-dependent relationship between word happiness and frequency.

PMID- 25997449
TI  - Metabolic dynamics analysis by massive data integration: application to tsunami
      affected field soils in Japan.
AB  - A new metabolic dynamics analysis approach has been developed in which massive
      data sets from time-series of (1)H and (13)C NMR spectra are integrated in
      combination with microbial variability to characterize the biomass degradation
      process using field soil microbial communities. On the basis of correlation
      analyses that revealed relationships between various metabolites and bacteria, we
      efficiently monitored the metabolic dynamics of saccharides, amino acids, and
      organic acids, by assessing time-course changes in the microbial and metabolic
      profiles during biomass degradation. Specific bacteria were found to support
      specific steps of metabolic pathways in the degradation process of biomass to
      short chain fatty acids. We evaluated samples from agricultural and abandoned
      fields contaminated by the tsunami that followed the Great East earthquake in
      Japan. Metabolic dynamics and activities in the biomass degradation process
      differed considerably between soil from agricultural and abandoned fields. In
      particular, production levels of short chain fatty acids, such as acetate and
      propionate, which were considered to be produced by soil bacteria such as
      Sedimentibacter sp. and Coprococcus sp., were higher in the soil from
      agricultural fields than from abandoned fields. Our approach could characterize
      soil activity based on the metabolic dynamics of microbial communities in the
      biomass degradation process and should therefore be useful in future
      investigations of the environmental effects of natural disasters on soils. 

PMID- 25997448
TI  - Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6
      interacting factor 1 promote the survival of human leukemic T cells.
AB  - Overexpression and hyperactivation of lymphocyte-specific protein tyrosine kinase
      (Lck) have been associated with leukemia development. We previously showed that,
      other than its known function as a cytoplasmic signal transducer, Lck also acts
      as a nuclear transcription factor in mouse leukemic cells. In the present study,
      we demonstrated the presence of nuclear Lck in human leukemic T cells and in
      primary cells. We further established a positive correlation between Lck nuclear
      localization and its kinase activity. Proteomic analysis identified CR6
      interacting factor 1 (CRIF1) as one of the Lck-interacting proteins. CRIF1 and
      Lck association in the nucleus was confirmed both by immunofluorescence
      microscopy and co-immunoprecipitation in human leukemic T cells. Close-range
      interaction between Lck and CRIF1 was validated by in situ proximity ligation
      assay (PLA). Consistent with the role of nuclear CRIF1 as a tumor suppressor,
      CRIF1 silencing promotes leukemic T cell survival in the absence of growth
      factors. This protective effect can be recapitulated by endogenous Lck or
      reconstituted Lck in leukemic T cells. All together, our results support a novel
      function of nuclear Lck in promoting human leukemic T cell survival through
      interaction with a tumor suppressor. It has important implications in defining a
      paradigm shift of non-canonical protein tyrosine kinase signaling.

PMID- 25997450
TI  - Association of urinary 3-phenoxybenzoic acid levels with self-reported depression
      symptoms in a rural elderly population in Asan, South Korea.
AB  - OBJECTIVES: This study aimed to evaluate the association between presence of
      depression symptoms and the exposure level to insecticides among aged population
      in rural area, determined via measured levels of urinary 3-phenoxybenzoic acid (3
      PBA), after controlling for socioeconomic confounding factors. METHODS: Using a
      cross-sectional study design, we randomly recruited participants for our study
      (161 male and 239 female) from rural areas of Asan, Chungnam, Korea.
      Environmental risk factor exposure was assessed using a questionnaire, and gas
      chromatography- mass spectrometry was used to analyze urinary 3-PBA levels. We
      used a logistic regression analysis to assess the association of urinary 3-PBA
      levels with the presence of self-reported depression symptoms. RESULTS: After
      controlling for creatinine levels, the median (interquartile range) concentration
      of 3-PBA was approximately 1.5 times (p<0.05) higher among female (1.54 [0.90 to
      2.35]) MUg/g) than among male (1.06 [0.64 to 1.81] MUg/g). Our study found that
      among female participants, the unit increase in 3-PBA levels exhibited a likely
      positive association (odds ratio, 1.12; 95% confidence interval, 1.00 to 1.25)
      with an increased risk of presence of self-reported depression symptoms, after
      adjusting for socioeconomic insurance type, daily physical condition, marital
      status, smoking status, and age. CONCLUSIONS: Given our finding of a potential
      association between the presence of selfreported depression symptoms and 3-PBA
      levels, precautions should be considered to minimize exposure to insecticides and
      thus protect the health of aged residents in rural areas.

PMID- 25997451
TI  - Neighbourhood socioeconomic disadvantage and fruit and vegetable consumption: a
      seven countries comparison.
AB  - BACKGROUND: Low fruit and vegetable consumption is a risk factor for poor health.
      Studies have shown consumption varies across neighbourhoods, with lower intakes
      in disadvantaged neighbourhoods. However, findings are inconsistent, suggesting
      that socio-spatial inequities in diet could be context-specific, highlighting a
      need for international comparisons across contexts. This study examined
      variations in fruit and vegetable consumption among adults from neighbourhoods of
      varying socioeconomic status (SES) across seven countries (Australia, Canada,
      Netherlands, New Zealand, Portugal, Scotland, US). METHODS: Data from seven
      existing studies, identified through literature searches and knowledge of co
      authors, which collected measures of both neighbourhood-level SES and fruit and
      vegetable consumption were used. Logistic regression was used to examine
      associations between neighbourhood-level SES and binary fruit and vegetable
      consumption separately, adjusting for neighbourhood clustering and age, gender
      and education. As much as possible, variables were treated in a consistent manner
      in the analysis for each study to allow the identification of patterns of
      association within study and to examine differences in the associations across
      studies. RESULTS: Adjusted analyses showed evidence of an association between
      neighbourhood-level SES and fruit consumption in Canada, New Zealand and
      Scotland, with increased odds of greater fruit intake in higher SES
      neighbourhoods. In Australia, Canada, New Zealand and Portugal, those residing in
      higher SES neighbourhoods had increased odds of greater vegetable intake. The
      other studies showed no evidence of a difference by neighbourhood-level SES.
      CONCLUSIONS: Acknowledging discrepancies across studies in terms of sampling,
      measures, and definitions of neighbourhoods, this opportunistic study, which
      treated data in a consistent manner, suggests that associations between diet and
      neighbourhood-level socioeconomic status vary across countries. Neighbourhood
      socioeconomic disadvantage may differentially impact on access to resources in
      which produce is available in different countries. Neighbourhood environments
      have the potential to influence behaviour and further research is required to
      examine the context in which these associations arise.

PMID- 25997452
TI  - Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to
      pathologic response following neoadjuvant therapy in HER2-positive breast cancer.
AB  - INTRODUCTION: A progressive loss of circulating anti-human epidermal growth
      factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is
      observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy
      controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab
      and chemotherapy (T + C) is associated with decreased recurrence and improved
      prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non
      pCR patients to identify modifiable immune correlates to pathologic response
      following neoadjuvant T + C. METHODS: Anti-HER2 Th1 responses in 87 HER2(pos)-IBC
      patients were examined using peripheral blood mononuclear cells pulsed with 6
      HER2-derived class II peptides via IFN-gamma ELISPOT. Th1 response metrics were
      anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative
      response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1
      responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1
      polarized dendritic cell (DC1) vaccination were analyzed pre- and post
      immunization. RESULTS: Depressed anti-HER2 Th1 responses observed in treatment
      naive HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated
      HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt,
      neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1
      repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not
      differ substantially in demographic/clinical characteristics, pCR patients
      demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p =
      0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response
      (148.2 vs. 22.4 SFC/10(6), p < 0.0001) versus non-pCR patients. After controlling
      for potential confounders, anti-HER2 Th1 responsivity remained independently
      associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN
      gamma(+) immune disparity was mediated by anti-HER2 CD4(+)T-bet(+)IFN-gamma(+)
      (i.e., Th1) - not CD4(+)GATA-3(+)IFN-gamma(+) (i.e., Th2) - phenotypes, and not
      attributable to non-pCR patients' immune incompetence, host-level T-cell anergy,
      or increased immunosuppressive populations. In recruited non-pCR patients, anti
      HER2 Th1 repertoire (3.7 vs. 0.5, p = 0.014) and cumulative response (192.3 vs.
      33.9 SFC/10(6), p = 0.014) improved significantly following HER2-pulsed DC1
      vaccination. CONCLUSIONS: Anti-HER2 CD4(+) Th1 response is a novel immune
      correlate to pathologic response following neoadjuvant T + C. In non-pCR
      patients, depressed Th1 responses are not immunologically "fixed" and can be
      restored with HER2-directed Th1 immune interventions. In such high-risk patients,
      combining HER2-targeted therapies with strategies to boost anti-HER2 Th1 immunity
      may improve outcomes and mitigate recurrence.

PMID- 25997453
TI  - Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and
      environmental risk factors.
AB  - INTRODUCTION: Specific environmental factors may play a role in the development
      of Pneumocystis pneumonia (PCP) in HIV-positive patients. The aim of this study
      was to estimate the PCP incidence and mortality in hospitalized HIV-positive
      patients in Spain during the combination antiretroviral therapy (cART) era (1997
      to 2011), as well as to analyze the climatological factors and air pollution
      levels in relation to hospital admissions and deaths. METHODS: We carried out a
      retrospective study. Data were collected from the National Hospital Discharge
      Database and the State Meteorological Agency of Spain. A case-crossover analysis
      was applied to identify environmental risk factors related to hospitalizations
      and deaths. For each patient, climatic factors and pollution levels were assigned
      based on readings from the nearest meteorological station to his or her postal
      code. RESULTS: There were 13,139 new PCP diagnoses and 1754 deaths in
      hospitalized HIV-positive patients from 1997 to 2011. The PCP incidence (events
      per 1000 person-years) dropped from 11.6 in 1997 to 2000, to 5.4 in 2004 to 2011
      (p<0.001). The mortality (events per 10,000 person-years) also decreased from
      14.3 in 1997 to 2000, to 7.5 in 2004 to 2011 (p<0.001). Most hospital admissions
      and deaths occurred in the winter season and the fewest occurred in the summer,
      overlapping respectively with the lowest and highest temperatures of the year in
      Spain. Moreover, lower temperatures prior to PCP admission, as well as higher
      concentrations of NO2 and particulate matter up to 10 m in size (PM10) at the
      time of admission were associated with higher likelihoods of hospital admission
      due to PCP when two weeks, one month, 1.5 months or two months were used as
      controls (p<0.01). Furthermore, higher concentrations of ozone at one month
      (p=0.007), 1.5 months (p<0.001) and two months (p=0.006) prior to admission were
      associated with higher likelihoods of hospital admission with PCP. For PCP
      related deaths, lower temperatures prior to admission and higher concentrations
      of atmospheric PM10 at the time of admission were related to higher likelihood of
      death when two weeks, one month and 1.5 months were used as controls (p<0.05).
      CONCLUSIONS: PCP was a significant health problem in the cART era (1997 to 2011),
      and PCP epidemiology was adversely influenced by colder climatological factors
      and higher ambient air pollution levels.

PMID- 25997454
TI  - Tumor regression and survival after perioperative MAGIC-style chemotherapy in
      carcinoma of the stomach and gastroesophageal junction.
AB  - BACKGROUND: We assessed the effectiveness of perioperative MAGIC-style
      chemotherapy in our series focused on the tumor regression grade and survival
      rate. METHODS: We conducted a retrospective study of 53 patients following a
      perioperative regimen of epirubicin, cisplatin, and fluorouracil or capecitabine
      (ECF/X). Forty-four (83 %) neoplasias were located in the stomach and 9 (17 %)
      were located at the esophagogastric junction. Perioperative chemotherapy
      completion, resection, TNM staging, the tumor regression grade (Becker's
      classification) and survival were analyzed. RESULTS: Forty-five patients (85 %)
      completed the 3 preoperative cycles. R0 resection was achieved in 42 (79 %)
      patients. Thirty-five (66 %) patients completed the 3 postoperative cycles. Nine
      carcinomas (17 %) were considered major responders after preoperative
      chemotherapy. With multivariate analysis, only completion of perioperative
      chemotherapy (HR: 0.25; 95%CI: 0.08 - 0.79; p = 0.019) was identified as an
      independent prognostic factor for disease-specific survival. However, the
      protective effect of perioperative therapy was lost in patients with ypT3-4 and
      more than 4 positive lymph nodes (HR: 1.16; 95%CI: 1.02 - 1.32; p = 0.029). The
      tumor regression grade (major vs minor responders) was at the limit of
      significance only with univariate analysis. The 5-year overall and disease
      specific survival rates were 18 % and 22 % respectively. CONCLUSIONS: The
      percentage of major responder tumors after preoperative chemotherapy was low.
      Completion of perioperative ECF/X chemotherapy may benefit patients with gastric
      carcinomas that do not invade the subserosa with few positive lymph nodes.

PMID- 25997455
TI  - Hypoxia-inducible factor-1alpha and Wnt/beta-catenin signaling pathways promote
      the invasion of hypoxic gastric cancer cells.
AB  - The present study aimed to examine the association between hypoxia-inducible
      factor (HIF)-1alpha and the Wnt/beta-catenin signaling pathway in a hypoxic
      environment. The study also aimed to explore the possible mechanisms underlying
      the invasion of hypoxic gastric cancer cells in vitro and in vivo. The pcDNATM
      6.2-GW/EmGFP-miR-beta-catenin plasmid was transfected into SGC-7901 gastric
      cancer cells, resulting in cells with stable suppression of beta-catenin
      expression. The biological characteristics of the control, liposome, negative
      control, beta-catenin knockdown, hypoxia and hypoxia beta-catenin knockdown
      groups were tested using an invasion assay. The differences in the invasive
      capacity of the control, negative control and liposome groups were not
      statistically significant. However, the hypoxia group demonstrated a
      significantly enhanced invasive capacity, as compared with that in the control
      group (P<0.05). In the hypoxia beta-catenin knockdown group, reduced cell
      penetration and diminished invasive behavior was observed (P<0.05). In the
      hypoxia and double (chemical + physical) hypoxia groups, HIF-1alpha, beta
      catenin, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase
      (MMP-7) protein and mRNA expression levels were elevated. In response to
      knockdown of beta-catenin expression, HIF-1alpha, beta-catenin, uPA and MMP-7
      protein as well as mRNA expression levels were significantly reduced in the
      hypoxia beta-catenin knockdown and the double hypoxia beta-catenin knockdown
      groups. In an in vivo experiment, the growth rate of xenograft tumors of hypoxic
      and control cells was high alongside increased HIF-1alpha, beta-catenin, uPA and
      MMP-7 levels according to western blot and immunohistochemical analyses, while
      growth and protein levels of tumors from hypoxic beta-catenin knockdown cells
      were significantly lower and those of beta-catenin knockdown cells were lowest.
      In conclusion, these results suggested that HIF-1alpha activation was able to
      regulate the Wnt/beta-catenin pathway, and that HIF-1alpha may be controlled by
      the Wnt/beta-catenin pathway. A potential mechanism underlying SGC-7901
      tumorigenicity is the activation of the Wnt/beta-catenin signaling pathway, which
      activates uPA and MMP-7 expression and contributes to the enhanced invasion of
      hypoxic cancer cells.

PMID- 25997456
TI  - Growth retardation at early life and metabolic adaptation among North Korean
      children.
AB  - The high prevalence of obesity is a major public health issue and contributes to
      the 'double burden' of disease in developing countries. Early exposure to poor
      nutrition may cause metabolic adaptations that, when accompanied by exposure to
      'affluent' nutrition, may increase the risk for obesity and other metabolic
      disorders. The aim of this study was to determine differences in energy
      metabolism and nutritional status between normal-height and growth-retarded North
      Korean children living in South Korea. A total of 29 children were recruited and
      underwent measurements of resting energy expenditure (REE), respiratory quotient
      (RQ), anthropometrics and dietary intake. There was no difference in REE or any
      assessment of obesity between the growth-retarded and normal-height children.
      Children who were classified as growth retarded (HAZ<-1.0) or stunted (HAZ<-2.0)
      had a significantly higher RQ (beta=0.036 or 0.060, respectively, P=0.018 or
      0.016), independent of sex, age, fat-free mass, fat mass and food quotient,
      compared with children with normal height. The results from this study, the first
      from an Asian population, add to the growing body of literature suggesting that
      undernutrition early in life results in adaptations in energy metabolism that
      favor fat deposition, increasing the risk of stunted children becoming overweight
      or obese later in life. Continued research on this topic is warranted, given the
      continued rise in the prevalence of the double burden in transitional countries. 

PMID- 25997457
TI  - Interactional role of microRNAs and bHLH-PAS proteins in cancer (Review).
AB  - MicroRNAs (miRNAs) are recognized as an emerging class of master regulators that
      regulate human gene expression at the post-transcriptional level and are involved
      in many normal and pathological cellular processes. Mammalian basic HLH (helix
      loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcriptional
      regulators that sense and respond to environmental signals (such as chemical
      pollutants) or to physiological signals (for instance hypoxia). In the normal
      state, bHLH-PAS proteins are responsible for multiple critical aspects of
      physiology to ensure the cell accurate homeostasis, but dysregulation of these
      proteins has been shown to contribute to carcinogenic events such as tumor
      initiation, promotion, and progression. Increasing epidemiological and
      experimental studies have shown that bHLH-PAS proteins regulate a panel of
      miRNAs, whereas some miRNAs also target bHLH-PAS proteins. The interaction
      between miRNAs and certain bHLH-PAS proteins [hypoxia-inducible factor (HIF) and
      aryl hydrocarbon receptor (AHR)] is relevant to many vital events associated with
      tumorigenesis. This review will summarize recent findings on the interesting and
      complicated underlying mechanisms that miRNAs interact with HIFs or AHR in
      tumors, hopefully to benefit the discovery of novel drug-interfering targets for
      cancer therapy. 

PMID- 25997459
TI  - THE BIOLOGICAL STATUS OF CHILDREN LIVING IN DISADVANTAGED REGIONS OF HUNGARY.
AB  - The aim of this study was to find out whether differences exist in the physical
      development, nutritional status and psychosomatic status of children living in
      deprived regions of Hungary compared with the Hungarian national reference
      values. The Hungarian government's decree No. 24/2003 created a complex indicator
      of social and economic conditions by which the country's regions were graded into
      deprived and non-deprived regions. This study examined 3128 children (aged 3-18
      years) living in the deprived regions and their biological status was compared
      with the national reference values (2nd Hungarian National Growth Study).
      Children's body development was assessed via some absolute body dimensions.
      Nutritional status was estimated by BMI with children being divided into
      'underweight', 'normal', 'overweight' and 'obese' categories. For children aged 7
      18 years a standard symptoms list was used to characterize psychosomatic status.
      The subjects were asked to rate their health status as excellent, good, fair or
      poor. The body development of children living in these deprived regions was
      significantly retarded compared with the national references in the age groups 7
      9 years and 14-17 years for boys and in the age groups 4-6 and 14-17 for girls.
      The prevalence of underweight was significantly higher in children and
      adolescents living in deprived regions (boys: 4.8%; girls: 5.9%) than the
      national references (boys: 2.9%; girls: 4.0%), while the prevalence of overweight
      and obese children did not differ between deprived regions (boys: 20.2%; girls:
      19.8%) and the national references (boys: 21.5%; girls: 19.1%). Children and
      adolescents living in the deprived regions rated their health status worse, and
      experienced more psychosomatic complaints (abdominal discomfort and fear), than
      the national references. Although the majority of body dimensions of children in
      deprived regions were close to the 50th centile of the Hungarian national
      references, a sizeable minority (31%) were 0.20SD or more away from the median
      value, which has implications as to how social, medical and public welfare policy
      can be shaped. 

PMID- 25997458
TI  - Clinical characteristics and patterns and predictors of response to therapy in
      collagenous and lymphocytic colitis.
AB  - BACKGROUND: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic
      inflammatory disorders of the colon. There is a paucity of data on differences in
      etiology, natural history, and treatment response between CC and LC. METHODS:
      Between 2002 and 2013, we identified new diagnoses of CC and LC using the
      Research Patient Data Registry in a tertiary referral center. We used chi square
      or Fischer's exact test and Wilcoxon rank-sum tests to compare the differences in
      clinical characteristics, treatment types, and response rates between LC and CC.
      RESULTS: Through 2013, we confirmed 131 patients with a new diagnosis of
      microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a
      diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have
      elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less
      likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective
      treatment for both CC and LC (94% and 80%, respectively). However, there were no
      statistically significant differences in response to various treatments according
      to the type of MC (all p > 0.10). Older age at the time of diagnosis was
      associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95%
      confidence interval: 1.21-2.56 for every 5-year increase) for both CC and LC.
      CONCLUSION: Despite differences in the clinical characteristics, response rates
      to available treatments appeared to be similar in both LC and CC. Older patients
      may have a better response to bismuth subsalicylate therapy.

PMID- 25997460
TI  - MicroRNA-26a-modified adipose-derived stem cells incorporated with a porous
      hydroxyapatite scaffold improve the repair of bone defects.
AB  - Tissue-engineered bone substitutes are frequently used to repair bone defects.
      Adipose-derived stem cells (ASCs) are a promising source of cells for repairing
      bone tissue, however, insufficient osteogenic potency remains the main obstacle
      for their application. The present study aimed to enhance the osteogenic potency
      of ASCs by transfection of microRNA (miR)-26a, a novel osteogenic and angiogenic
      promoting miRNA. An inverted fluorescence microscope was used to observe
      transfection efficiency, while a scanning electron microscope was used to detect
      morphological alterations. Cell proliferation was monitored continuously for 7
      days using a Cell Counting kit-8 assay. Osteogenic differentiation was determined
      by reverse transcription quantitative polymerase chain reaction, alkaline
      phosphatase (ALP) staining, collagen secretion and extracellular matrix (ECM)
      mineralization. ASCs were incorporated with a porous hydroxyapatite (HA) scaffold
      to create a novel tissue-engineered bone substitute and inserted into the
      critical tibia defect of rats. New bone formation was evaluated by hematoxylin
      and eosin and Masson's trichrome staining. The results demonstrated that miR-26a
      was successfully delivered into the cytoplasm, while the morphology and
      proliferation of ASCs were not significantly altered. Osteogenic-associated genes
      were markedly upregulated and ALP production, collagen secretion and ECM
      mineralization were all increased following transfection of miR-26a. Histological
      evaluation demonstrated that the modified cells accompanied with a porous HA
      scaffold markedly promoted new bone formation within the defective area. In
      conclusion, miR-26a transfection significantly improved the osteogenic potency of
      ASCs suggesting that modified ASCs incorporated with a HA scaffold may be used as
      a potential bone substitute.

PMID- 25997462
TI  - Cognitive impulsivity and the development of delinquency from late childhood to
      early adulthood: Moderating effects of parenting behavior and peer relationships.
AB  - Cognitive impulsivity may increase children's risk of developing delinquent
      behavior. However, the influence of cognitive impulsivity may depend on social
      environmental risk factors. This study examined the moderating effect of late
      childhood parenting behaviors and peer relations on the influence of children's
      cognitive impulsivity on delinquency development across adolescence and early
      adulthood, while taking possible interactions with intelligence also into
      account. Delinquent behavior of 412 boys from the Pittsburgh Youth Study was
      measured annually from ages 13 to 29 years with official arrest records.
      Cognitive impulsivity (neurocognitive test scores) and intelligence were assessed
      at age 12-13. Parenting behaviors (persistence of discipline, positive
      reinforcement, and parental knowledge), peer delinquency, and peer conventional
      activities were assessed between ages 10 and 13 years. Results showed that, while
      controlling for intelligence, the influence of youths' cognitive impulsivity on
      delinquency depended on their parents' behaviors. An interaction was found among
      cognitive impulsivity, intelligence, and peer delinquency, but instead of
      cognitive impulsivity, the effect of intelligence on delinquency was particularly
      moderated. Overall, findings suggest that when there was moderation, high
      cognitive impulsivity and low intelligence were associated with an increased
      probability for engaging in delinquency predominantly among boys in a good social
      environment, but not in a poor social environment. 

PMID- 25997461
TI  - The C-terminal region of the RNA helicase CshA is required for the interaction
      with the degradosome and turnover of bulk RNA in the opportunistic pathogen
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a versatile opportunistic pathogen that adapts readily
      to a variety of different growth conditions. This adaptation requires a rapid
      regulation of gene expression including the control of mRNA abundance. The CshA
      DEAD-box RNA helicase was previously shown to be required for efficient turnover
      of the agr quorum sensing mRNA. Here we show by transcriptome-wide RNA sequencing
      and microarray analyses that CshA is required for the degradation of bulk mRNA.
      Moreover a subset of mRNAs is significantly stabilised in absence of CshA.
      Deletion of the C-terminal extension affects RNA turnover similar to the full
      deletion of the cshA gene. In accordance with RNA decay data, the C-terminal
      region of CshA is required for an RNA-independent interaction with components of
      the RNA degradation machinery. The C-terminal truncation of CshA reduces its
      ATPase activity and this reduction cannot be compensated at high RNA
      concentrations. Finally, the deletion of the C-terminal extension does affect
      growth at low temperatures, but to a significantly lesser degree than the full
      deletion, indicating that the core of the helicase can assume a partial function
      and opening the possibility that CshA is involved in different cellular
      processes. 

PMID- 25997463
TI  - Free availability of high-energy foods led to energy over-ingestion and protein
      under-ingestion in choice-fed broilers.
AB  - The objective of this study was to compare energy and protein content of the diet
      selected by choice-fed broilers with that of broilers fed a balanced diet. One
      hundred and eighty 1-day-old male broilers were randomly assigned in groups of 10
      to one of three experimental treatments (n = 6). Control broilers were fed a
      standard balanced diet, whereas choice-fed broilers were fed three foods which
      were more concentrated (Choice C+ treatment) or less concentrated (Choice C-
      treatment) in protein, carbohydrate or fat. We evaluated food intake behavior,
      nutrient intake, and performance parameters of broilers from 2 to 7 weeks of age.
      Choice C+ broilers showed enhanced preference for the high-fat food, which led to
      higher energy intake and lower protein intake than those of control broilers at 2
      to 4 weeks of age. Body weight, weight gain and feed conversion efficiency were
      negatively affected by diet selection of Choice C+ broilers. Choice C- broilers
      selected a balanced diet, and showed performance parameters similar to those of
      control broilers. Our results supported the hypothesis that free availability of
      high-energy foods bias ingestive behavior of choice-fed broilers toward selecting
      a diet with higher energy and lower protein than needed for normal growth. 

PMID- 25997465
TI  - A Meta-Analysis of the Association between Helicobacter pylori Infection and Risk
      of Coronary Heart Disease from Published Prospective Studies.
AB  - BACKGROUND: The association between helicobacter pylori (Hp) infection and
      coronary heart disease (CHD) has long been debated, and the results from previous
      meta-analysis are varied. AIMS: The aim for this study was to identify the
      association between Hp and CHD using published perspective cohort studies.
      MATERIALS AND METHODS: A systematic review and meta-analysis were performed on
      studies published from January, 1992 to April, 2014. All studies included used
      data from prospective cohort studies of CHD events or CHD deaths. Random effect
      models were applied in all estimations. RESULTS: H. pylori infection increased
      the risk of CHD events by 11% (19 studies, n = 22,207, risk ratio (RR) = 1.11,
      95% confidence interval (CI): 1.01-1.22). This effect was greater for studies
      that had less than 5 years' follow-up time (RR = 1.15, 95% CI: 1.00-1.32).
      However, this effect was not significant for studies that had follow-up times
      >=10 years (n = 5100, RR = 1.04, 95% CI: 0.87-1.24). Neither Cag-A seropositive
      nor Cag-A seronegative strains of H. pylori were associated with a significantly
      increased risk of CHD events or deaths based on the current published data.
      CONCLUSION: In conclusion, H. pylori infection increased the risk of CHD events,
      especially in a patient's early life, but this association was weaker or might be
      masked by other CHD risk factors in long-term observations.

PMID- 25997466
TI  - Eruptive squamous cell carcinomas with keratoacanthoma-like features in a patient
      treated with ruxolitinib.

PMID- 25997467
TI  - Genome-wide SNP data show little differentiation between the Appaloosa and other
      American stock horse breeds.

PMID- 25997464
TI  - Balancing the risks of hydraulic failure and carbon starvation: a twig scale
      analysis in declining Scots pine.
AB  - Understanding physiological processes involved in drought-induced mortality is
      important for predicting the future of forests and for modelling the carbon and
      water cycles. Recent research has highlighted the variable risks of carbon
      starvation and hydraulic failure in drought-exposed trees. However, little is
      known about the specific responses of leaves and supporting twigs, despite their
      critical role in balancing carbon acquisition and water loss. Comparing healthy
      (non-defoliated) and unhealthy (defoliated) Scots pine at the same site, we
      measured the physiological variables involved in regulating carbon and water
      resources. Defoliated trees showed different responses to summer drought compared
      with non-defoliated trees. Defoliated trees maintained gas exchange while non
      defoliated trees reduced photosynthesis and transpiration during the drought
      period. At the branch scale, very few differences were observed in non-structural
      carbohydrate concentrations between health classes. However, defoliated trees
      tended to have lower water potentials and smaller hydraulic safety margins. While
      non-defoliated trees showed a typical response to drought for an isohydric
      species, the physiology appears to be driven in defoliated trees by the need to
      maintain carbon resources in twigs. These responses put defoliated trees at
      higher risk of branch hydraulic failure and help explain the interaction between
      carbon starvation and hydraulic failure in dying trees. 

PMID- 25997468
TI  - Indole Functionalization via Photoredox Gold Catalysis.
AB  - The use of photoredox catalyst [Au2(dppm)2]Cl2 to initiate free-radical
      cyclizations onto indoles is reported. Excitation of the dimeric Au(I)
      photocatalyst for the reduction of unactivated bromoalkanes and bromoarenes is
      used for the generation of carbon-centered radicals. Previous to this work,
      reduction processes leading to indole functionalization utilizing photoredox
      catalysts were limited to activated benzylic or alpha-carbonyl-positioned
      bromoalkanes. This method offers a mild and safe alternative to organostannanes
      and pyrophoric initiators for access to high energy radicals that were previously
      inaccessible through catalytic or stoichiometric means. 

PMID- 25997469
TI  - Metabolomics and Proteomics, and What to Do with All These 'Omes': Insights from
      Nutrigenomic Investigations in New Zealand.
AB  - BACKGROUND/AIMS: Nutrigenomics New Zealand has invested considerable effort
      researching the role of nutrient-gene interactions in human inflammatory bowel
      disease (IBD). This research has utilised a number of 'omics' techniques,
      including proteomics and metabolomics. METHODS: Mouse models of intestinal
      inflammation have been used to investigate the mechanisms underlying IBD and to
      test foods or food components for potential beneficial effects. Proteomics
      combining two-dimensional gel electrophoresis with liquid chromatography-mass
      spectrometry (LC-MS) analysis of peptides, and metabolomics using both gas
      chromatography-MS and LC-MS have been combined with transcriptomics and
      microbiome analyses to comprehensively assess samples derived from these models.
      RESULTS: Across several independent studies, we have identified key proteins and
      metabolites which are involved in chronic inflammation. We have also identified
      food compounds such as polyphenols (green tea polyphenols or curcumin) and
      polyunsaturated fatty acids, or whole foods such as salmon and broccoli, that
      reduce inflammation by regulating the activity of these proteins and metabolites.
      CONCLUSIONS: Omics techniques, including proteomics and metabolomics, have
      deepened our insight into the mechanisms underlying intestinal inflammation, and
      how nutrient-gene interactions may influence these. However, challenges remain in
      dealing with the enormous quantity of data generated by these techniques, and in
      utilising these data to improve the outcome for people with IBD.

PMID- 25997470
TI  - Quercetin-induced autophagy flux enhances TRAIL-mediated tumor cell death.
AB  - Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in
      fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell
      cycle arrest and is a well known cancer therapeutic agent and autophagy mediator.
      We investigated whether quercetin enhances TRAIL-induced tumor cell death and the
      possible mechanism in human lung cancer cells. We identified that quercetin
      markedly enhanced TRAIL-mediated lung cancer cell death. Quercetin treatment dose
      dependently decreased the p62 protein expression and increased GFP-LC3B.
      Autophagy flux inhibitor, chloroquine treatment blocked the enhancing effects of
      TRAIL-induced apoptosis by quercetin. Our results indicated that quercetin
      enhanced TRAIL-induced cell death via autophagy flux activation, and also suggest
      that quercetin may be a therapeutic agent against human lung cancer via
      combination therapy with many anticancer drugs including TRAIL. 

PMID- 25997471
TI  - Generalized drug eruption as "third-party-induced" health damage pursuant to
      Article 294a of the German Social Code, Volume 5 (SGB V).

PMID- 25997472
TI  - Intestinal Surgery for Crohn's Disease: Role of Preoperative Therapy in
      Postoperative Outcome.
AB  - PURPOSES: Patients affected by Crohn's disease (CD) require lifelong medical
      therapy, but they can also often require abdominal surgery. The effect of CD
      therapy on postoperative course is still unclear. The aim of this study was to
      evaluate the effect of preoperative medical therapy on the outcome of intestinal
      surgery in these patients. METHODS: Data from a consecutive series of 167
      patients with CD operated on at the University of Padova Hospital from 2000 to
      2013 were retrieved. Data of preoperative therapy during the 6 months before
      surgery were available for 146 patients who were enrolled in this retrospective
      study. Clinical data and surgical details were retrieved and postoperative
      complications and reoperation were considered outcome measures. Univariate and
      multivariate analysis were performed. RESULTS: No significant difference was
      observed between patients without data about their preoperative therapy and those
      with them. Eight patients underwent reoperation in the first 30 postoperative
      days: two of them for anastomotic leak, three for bleeding, one for obstruction
      and two for abdominal wound dehiscence. At multivariate analysis, preoperative
      adalimumab and budesonide resulted to be an independent predictor of reoperation
      (OR = 7.67 (95% CI = 1.49-39.20), p = 0.01 and OR = 6.7749 (95% CI = 0.98-46.48),
      p = 0.05, respectively). At multivariate analysis neither pharmacological nor
      clinical variables resulted to predict anastomotic leak. CONCLUSIONS: In our
      series, adalimumab seemed to be associated to early reoperation after intestinal
      surgery. This may be due to a worst disease severity in patients who needed
      surgery in spite of biological therapy. Preoperative tapering of budesonide dose
      seems a safe option before elective abdominal surgery for CD.

PMID- 25997473
TI  - Frequency of TERT Promoter Mutations in Prostate Cancer.
AB  - OBJECTIVE: Recently, recurrent mutations within the core promoter of the human
      telomerase reverse transcriptase (TERT) gene generating consensus binding sites
      for ETS transcription factor family members were described in melanomas and other
      malignancies (e.g. bladder cancer, hepatocellular carcinoma). These mutations
      were discussed as early drivers for malignant transformation. In prostate cancer
      (PrCa) TERT expression has been associated with a poor prognosis and higher risk
      for disease recurrence. The underlying mechanisms for high TERT expression in
      PrCa have still not been clarified. To date, data on TERT promoter mutation
      analysis in PrCa are sparse. Therefore, we performed sequence analysis of the
      core promoter region of the TERT gene in an unselected cohort of prostate tumors.
      METHODS: Sections from 167 formalin-fixed, paraffin-embedded and cryopreserved
      prostate tumors were microdissected and used for DNA isolation. The mutation
      hotspot region within the TERT core promoter (-260 to +60) was analyzed by direct
      Sanger sequencing or SNaPshot analysis. RESULTS: All cases were analyzed
      successfully. Mutations within the core promoter of the TERT gene were not
      detected in any of the cases with all tumors exhibiting a wild-type sequence.
      CONCLUSION: TERT core promoter mutations reported from several other malignancies
      were not detected in our unselected cohort of PrCa. These data indicate that
      alterations within the core promoter of the TERT gene do not play an important
      role in prostate carcinogenesis.

PMID- 25997474
TI  - Framing the relationship between people and nature in the context of European
      conservation.
AB  - A key controversy in conservation is the framing of the relationship between
      people and nature. The extent to which the realms of nature and human culture are
      viewed as separate (dualistic view) or integrated is often discussed in the
      social sciences. To explore how this relationship is represented in the practice
      of conservation in Europe, we considered examples of cultural landscapes,
      wildlife (red deer, reindeer, horses), and protected area management. We found
      little support, for a dualistic worldview, where people and nature are regarded
      as separate in the traditional practice of conservation in Europe. The borders
      between nature and culture, wild and domestic, public land and private land, and
      between protected areas and the wider landscape were blurred and dynamic. The
      institutionalized (in practice and legislation) view is of an interactive
      mutualistic system in which humans and nature share the whole landscape. However,
      more dualistic ideals, such as wilderness and rewilding that are challenging
      established practices are expanding. In the context of modern day Europe,
      wilderness conservation and rewilding are not valid for the whole landscape,
      although it is possible to integrate some areas of low-intervention management
      into a wider matrix. A precondition for success is to recognize and plan for a
      plurality of values concerning the most valid approaches to conservation and to
      plan for this plurality at the landscape scale. 

PMID- 25997475
TI  - Long-term results of the cutting seton for high anal fistula.
AB  - BACKGROUND: No single procedure for high anal fistula delivers a high cure rate
      while also completely protecting sphincter function. This paper reports our long
      term results with the cutting seton for high fistulae and draws comparisons with
      advancement flap and ligation of intersphincteric fistula track (LIFT)
      procedures. METHODS: A retrospective study of prospectively collected data in
      consecutive patients undergoing treatment with cutting seton for high
      cryptoglandular fistulae was carried out. A strict protocol dictated tightening
      intervals of at least 4 weeks and no muscle division. In 59 patients (male :
      female = 39:20) followed-up at mean 9.4 years (range 1.7-15.6 years) healing
      rates, continence (St Mark's score 0-24), patient-perceived overall change in
      bowel control (-5 to +5), faecal incontinence quality of life (FIQL) and overall
      patient satisfaction (visual analogue score 0-10) were assessed. RESULTS: Primary
      and secondary healing rates were 93% and 98%. Mean continence score was 4.1,
      significantly worse in women than men (median 6, range 0-22 versus median 1,
      range 0-17; P = 0.006). Seventy-eight per cent of patients had normal continence
      or minor incontinence (score 0-6), 13.5% moderate incontinence (score 7-12) and
      8.5% severe incontinence (score >12). Sixty-three per cent of patients had no
      change or improved patient-perceived overall bowel control. Mean FIQL scores were
      high and significantly correlated with continence. Median satisfaction score was
      9. CONCLUSION: Cutting seton for high anal fistula achieved healing in 98% with
      good continence in the majority, particularly in males, and a high level of
      patient satisfaction. Multicentre prospective studies are needed to adequately
      compare cutting seton, flap and LIFT procedures.

PMID- 25997476
TI  - Historical evolution of the frontal lobe syndrome.
AB  - The function of the frontal lobes and the related frontal lobe syndrome have not
      been described in detail until relatively late in history. Slowly, the
      combination of knowledge from animal models, the detailed examination of symptoms
      after traumatic frontal lobe injuries, and the rise and fall of psychosurgery has
      led to increasing insight into frontal lobe function. The frontosubcortical
      circuits have been described and increasingly related to clinical syndromes,
      confirmed by the latest developments in functional connectivity networks.

PMID- 25997477
TI  - Severe Acute Subdural Hematoma in a Child following a Minor Head Trauma in the
      Context of a Recent Antecedent Head Injury: A Case Report.
AB  - Knowledge of the force required to generate a subdural hematoma is important when
      considering the veracity of histories given by family members of young children.
      Traditional wisdom is that a substantial impact is required to cause an acute
      subdural hematoma. We present a case of acute subdural hematoma following a low
      level fall in a 3-year-old patient. An antecedent head injury associated with
      normal CT scan might have had some bearing on this outcome.

PMID- 25997478
TI  - The Effects of Climate Change on Cardiac Health.
AB  - The earth's climate is changing and increasing ambient heat levels are emerging
      in large areas of the world. An important cause of this change is the
      anthropogenic emission of greenhouse gases. Climate changes have a variety of
      negative effects on health, including cardiac health. People with pre-existing
      medical conditions such as cardiovascular disease (including heart failure),
      people carrying out physically demanding work and the elderly are particularly
      vulnerable. This review evaluates the evidence base for the cardiac health
      consequences of climate conditions, with particular reference to increasing heat
      exposure, and it also explores the potential further implications.

PMID- 25997479
TI  - How to quantify binaural hearing in patients with unilateral hearing using
      hearing implants.
AB  - Application of bilateral hearing devices in bilateral hearing loss and unilateral
      application in unilateral hearing loss (second ear with normal hearing) does not
      a priori lead to binaural hearing. An overview is presented on several measures
      of binaural benefits that have been used in patients with unilateral or bilateral
      deafness using one or two cochlear implants, respectively, and in patients with
      unilateral or bilateral conductive/mixed hearing loss using one or two
      percutaneous bone conduction implants (BCDs), respectively. Overall, according to
      this overview, the most significant and sensitive measure is the benefit in
      directional hearing. Measures using speech (viz. binaural summation, binaural
      squelch or use of the head shadow effect) showed minor benefits, except for
      patients with bilateral conductive/mixed hearing loss using two BCDs. Although
      less feasible in daily practise, the binaural masking level difference test seems
      to be a promising option in the assessment of binaural function.

PMID- 25997480
TI  - Foodies of Innate Immunity.

PMID- 25997481
TI  - Fasudil Stimulates Neurite Outgrowth and  Promotes Differentiation in C17.2
      Neural  Stem Cells by Modulating Notch Signalling  but not Autophagy.
AB  - BACKGROUND: Neurite outgrowth is one of the important therapeutic strategies for
      neuronal plasticity and regeneration in neural disorders. Fasudil is a clinical
      medication that is used to treat subarachnoid haemorrhage (SAH) and that is
      beneficial for many animal models of central nervous system (CNS) diseases. In
      this study, we hypothesised that fasudil administration would promote neurite
      outgrowth in neural stem cells (NSCs). METHODS: Changes in cell morphology were
      imaged under a light microscope, and neurite-bearing cells were counted. Cell
      viability and the necrosis rate were determined by MTT and LDH assays,
      respectively. Additionally, western blot and immunofluorescence analyses were
      performed to detect protein expression levels. RESULTS: We found that fasudil
      promoted neurite outgrowth in C17.2 cells in a time- and dose-dependent manner.
      The neurite-bearing C17.2 cells were differentiated by detecting the changes in
      neural and astrocytic markers after fasudil treatment through down-regulating
      Notch signalling. Previously, fasudil was reported to induce autophagy, which
      plays an important role in neural differentiation. However, both rapamycin, an
      autophagy inducer, and 3-methyl-adenine (3-MA), an autophagy inhibitor, had no
      effects on the fasudil-induced neurite outgrowth, suggesting that autophagy may
      be not involved in this process. CONCLUSION: In summary, fasudil could stimulate
      neurite outgrowth and differentiation in C17.2 cells by modulating Notch
      signalling but not autophagy.

PMID- 25997482
TI  - Management of Cytomegalovirus Seroconversion during Pregnancy in France.
AB  - INTRODUCTION: Guidelines for the management of cytomegalovirus (CMV) infection of
      the fetus are rare. Our main objective was to evaluate how health care
      practitioners in France manage cases of CMV seroconversion during pregnancy.
      MATERIAL AND METHODS: A questionnaire was e-mailed to health care practitioners
      potentially concerned by CMV seroconversion during pregnancy. They were asked if
      they would recommend amniocentesis, fetal cerebral MRI examination and fetal
      blood analysis (FBA), depending on the ultrasound results. They then had to
      indicate whether they would accept termination of pregnancy (TOP), depending on
      the results of these examinations. RESULTS: A total of 380 health care
      practitioners responded, mainly obstetricians (73.9%) and midwives (20.2%).
      Overall, 57% of respondents recommended amniocentesis in the case of CMV
      seroconversion during the first trimester of pregnancy, ultrasound findings being
      normal. In cases of positive amniocentesis and a major ultrasound abnormality,
      84.5% of respondents would perform cerebral MRI, and 44.4% would perform FBA. In
      this case, the rate of acceptance of TOP was not significantly different whether
      the examinations were normal (337/372, 90.6%) or not performed (339/374, 93.3%; p
      = 0.17). DISCUSSION: Amniocentesis is too infrequently used and should be
      encouraged. The results of MRI and FBA are often not taken into account in the
      final decision concerning TOP. Guidelines are needed to clarify the management of
      CMV seroconversion during pregnancy.

PMID- 25997483
TI  - Anthropology and mental health care.

PMID- 25997484
TI  - [Severe/moderate hypothermia in a female patient found in a snowdrift].

PMID- 25997485
TI  - [Sarcoidosis--underevaluated cause of malignant ventricular arrhythmias].

PMID- 25997486
TI  - Acute coronary syndrome in a patient with an anomaly of the right coronary
      artery, which originated from the medial part of the left anterior descending
      artery.

PMID- 25997487
TI  - Complex interventional treatment in a patient with cardiogenic stroke.

PMID- 25997488
TI  - Unexpected finding of a single persistent left superior vena cava during medical
      events following transcatheter aortic valve implantation.

PMID- 25997489
TI  - Hybrid approach for acute limb ischaemia after transcatheter aortic valve
      implantation.

PMID- 25997490
TI  - Mitral stenosis with giant left atrial thrombus obstructing pulmonary veins.

PMID- 25997491
TI  - Lead-dependent infective endocarditis with a giant vegetation in the heart around
      an externalised VDD pacing lead. VDD lead externalisation in the course of
      tribological lead wear.

PMID- 25997492
TI  - Decreased tricuspid annular peak systolic velocity (S') and N-terminal B-type
      natriuretic pro-peptide values in children after tetralogy of Fallot repair.

PMID- 25997493
TI  - Docosahexaenoic acid inhibits the growth of hormone-dependent prostate cancer
      cells by promoting the degradation of the androgen receptor.
AB  - Epidemiological and preclinical data have demonstrated the preventative effects
      of omega-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), on
      prostate cancer. However, there are inconsistencies in these previous studies and
      the underlying mechanisms remain to be elucidated. In the present study, the
      androgen receptor (AR), which is a transcription factor involved in cell
      proliferation and prostate carcinogenesis, was identified as a target of DHA. It
      was revealed that DHA inhibited hormone-dependent growth of LNCaP prostate cancer
      cells. Reverse transcription-quantitative polymerase chain reaction analysis
      revealed that treatment with DHA caused no alteration in the transcribed mRNA
      expression levels of the AR gene. However, immunoblotting revealed that this
      treatment reduces the protein expression level of the AR. The androgen-induced
      genes were subsequently repressed by treatment with DHA. It was demonstrated that
      DHA exhibits no effect on the translation process of the AR, however, it promotes
      the proteasome-mediated degradation of the AR. Therefore, the present study
      provided a novel mechanism by which DHA exhibits an inhibitory effect on growth
      of prostate cancer cells.

PMID- 25997494
TI  - Modulation of uPA, MMPs and their inhibitors by a novel nutrient mixture in human
      colorectal, pancreatic and hepatic carcinoma cell lines.
AB  - Colorectal, pancreatic and hepatic carcinomas are characterized by high levels of
      matrix metalloproteinase (MMP)-2 and -9 secretions, allowing cancer cells to
      spread to distal organs. These and other proteases, such as uPA, play a key role
      in tumor cell invasion and metastasis by digesting the basement membrane and ECM
      components. Strong clinical and experimental evidence demonstrates association of
      elevated levels of uPA and MMPs with cancer progression, metastasis and shortened
      patient survival. MMP activities are regulated by specific tissue inhibitors of
      metalloproteinases (TIMPs). Our main objective was to study the effect of a
      nutrient mixture (NM) on activity of uPA, MMPs and TIMPs in colon HCT-116,
      pancreatic MIA PaCa-2 and hepatic carcinoma SK-Hep-1 cell lines. These cell lines
      (ATCC) were cultured in their respective media and treated at confluence with NM
      at 0, 50, 100, 250, 500 and 1000 ug/ml. Analysis of uPA activity was carried out
      by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse
      zymography. All three cancer cell lines expressed uPA, which was inhibited by NM
      in a dose-dependent manner. On gelatinase zymography, SK-Hep-1 showed bands
      corresponding to MMP-2 and MMP-9 with enhancement of MMP-9 with PMA (100 ng/ml)
      treatment. HCT-116 and MIA PaCa-2 showed strong bands corresponding to MMP-9 but
      no MMP-2 band. NM inhibited their expression in a dose-dependent manner. Activity
      of TIMPs was upregulated by NM in all cancer cell lines in a dose-dependent
      manner. Analysis revealed a positive correlation between uPA and MMP-9 and a
      negative correlation between uPA/MMP-9 and TIMP-2. These findings suggest the
      therapeutic potential of NM in treatment of colon, pancreatic and hepatic
      carcinomas. 

PMID- 25997496
TI  - CHANGES IN MARRIAGE PATTERNS AMONG THE ARAB COMMUNITY IN ISRAEL OVER A 60-YEAR
      PERIOD.
AB  - The aim of this study was to determine the prevalence and trends of various types
      of consanguineous marriage among the Arab community in Israel over a long time
      period (1948-2007) by religion and educational level. Data were collected by face
      to-face interview of 3173 Arab couples living in Israel in 2007 and 2008. The
      trend in consanguineous marriages was found to decrease significantly over
      successive time periods, from 42.5% to 30.9% (p=0.001), and the prevalence of
      first-cousin and closer marriages decreased, from 23% to 12.7%. Consanguinity was
      found to be significantly related to religion (p=0.001) and wife's level of
      education (p=0.028). 

PMID- 25997495
TI  - Continuous expression of CD83 on activated human CD4+ T cells is correlated with
      their differentiation into induced regulatory T cells.
AB  - CD83 is a widely recognized surface marker for mature dendritic cells, which are
      essential for priming naive CD4+ T cells into effector cells. However, CD83 is
      also expressed on activated CD4+ T cells, which remains an enigma in T-cell
      mediated immunity. Therefore, the identification of the biological features and
      regulation of the expression of CD83 on activated CD4+ T cells is important in
      understanding the function of CD83 in the adaptive immune response. The present
      study revealed a time-dependent manner of the expression of CD83 on anti-CD3/CD28
      stimulated human CD4+ T cells, which is characterized by the maximum expression
      at day 2 and a significant decrease at day 3. The reduced expression is not a
      result of a reduced rate of cell proliferation. The activation of interleukin-2
      and secretion of interferon-gamma accumulated progressively from day 1 to 3. Of
      note, sustained expression of CD83 was observed when CD4+ T cells were induced by
      transforming growth factor-beta to differentiate into CD4+CD25+ forkhead box P3+
      regulatory T (iTreg) cells. Confocal immunofluorescence microscopy analysis
      demonstrated that CD83 was highly co-localized with CD25 on activated CD4+ T
      cells. In conclusion, the findings of the present study suggested that the
      continuous expression of CD83 on activated human CD4+ T cells is correlated with
      their differentiation into iTreg cells. 

PMID- 25997497
TI  - Discontinuation of alpha-interferon treatment in patients with chronic myeloid
      leukemia in long-lasting complete molecular response.
AB  - To evaluate follow-up after alpha-interferon (IFN) discontinuation, 23 patients
      with chronic myeloid leukemia (CML) in stable complete molecular response (CMolR)
      with IFN were revisited. After a median IFN treatment of 105.8 months (IR 56.1 -
      127.3), all patients discontinued IFN for prolonged CMolR (12), intolerance (8)
      or planned ABMT (3). After 12.5 months, one patient developed an extramedullar
      blast crisis. Four patients needed to start imatinib, all achieving again
      molecular response. Eighteen patients are still off-therapy (median time from IFN
      discontinuation 125.5 months, IR 86.9-205.3); among these, five are BCR-ABL
      negative, six present with a sporadic positivity (BCR-ABL ratio < 0.1) and seven
      show a stable and long-lasting mild positivity (BCR-ABL ratio < 0.5). Patients in
      prolonged CMolR with IFN have low risk of recurrence after discontinuation; the
      reappearance of a BCR-ABL positivity < 0.5 did not always precede a relapse,
      suggesting mechanisms of immunological control induced by IFN. 

PMID- 25997498
TI  - Garlic (A. sativum L.) alliinase gene family polymorphism reflects bolting types
      and cysteine sulphoxides content.
AB  - BACKGROUND: Alliinase is an important enzyme occurring in Allium species that
      converts precursors of sulfuric compounds, cysteine sulfoxides into a
      biologically active substance termed allicin. Allicin facilitates garlic defense
      against pests and produces health-promoting compounds. Alliinase is encoded by
      members of a multigene family that has not yet been sufficiently characterized,
      namely with regard to the copy numbers occurring within the genome and the
      polymorphisms among the family members. RESULTS: We cloned 45 full-length
      alliinase amplicons of cultivar (cv.) Jovan. Sequence analyses revealed nine
      different sequence variants (SVs), confirming the multilocus nature of this gene
      family. Several mutations in exons, mainly occurring in the first exon coding for
      vacuolar signal peptide, were found. These results enabled us to identify
      sequences with putatively modified vacuole-targeting abilities. We found
      additional sequence variants using partial amplicons. We estimated that the
      minimum number of gene copies in the diploid genome of the investigated cultivar
      was fourteen. We obtained similar results for another three cultivars, which
      differed in bolting type and place of origin. The further identification of high
      degree of polymorphisms in the intron regions allowed us to develop a specific
      polymerase chain reaction assay capable to capture intron length polymorphism
      (ILP). This assay was used to screen 131 additional accessions. Polymorphic data
      were used for cluster analysis, which separated the bolting and non-bolting
      garlic types and those with high cysteine-sulfoxide contents in a similar way as
      AFLP analysis in previous study. These newly developed markers can be further
      applied for the selection of desirable garlic genotypes. CONCLUSIONS: Detailed
      analysis of sequences confirmed multigenic nature of garlic alliinase. Intron and
      exon polymorphism analysis generated similar results as whole genome variability
      assessed previously by AFLP. Detected polymorphism is thus also associated with
      cysteine-sulphoxide content in individual genotypes. ILP markers capable to
      detect intron polymorphisms were newly developed. Developed markers could be
      applied in garlic breeding. Higher genetic variability found in bolting genotypes
      may indicates longer period of their sexual propagation in comparison with
      nonbolting genotypes.

PMID- 25997499
TI  - Manipulation of the hypocotyl sink activity by reciprocal grafting of two
      Raphanus sativus varieties: its effects on morphological and physiological traits
      of source leaves and whole-plant growth.
AB  - To reveal whether hypocotyl sink activities are regulated by the aboveground
      parts, and whether physiology and morphology of source leaves are affected by the
      hypocotyl sink activities, we conducted grafting experiments using two Raphanus
      sativus varieties with different hypocotyl sink activities. Comet (C) and Leafy
      (L) varieties with high and low hypocotyl sink activities were reciprocally
      grafted and resultant plants were called by their scion and stock such as CC, LC,
      CL and LL. Growth, leaf mass per area (LMA), total non-structural carbohydrates
      (TNCs) and photosynthetic characteristics were compared among them. Comet
      hypocotyls in CC and LC grew well regardless of the scions, whereas Leafy
      hypocotyls in CL and LL did not. Relative growth rate was highest in LL and
      lowest in CC. Photosynthetic capacity was correlated with Rubisco (ribulose 1.5
      bisphosphate carboxylase/oxygenase) content but unaffected by TNC. High C/N ratio
      and accumulation of TNC led to high LMA and structural LMA. These results showed
      that the hypocotyl sink activity was autonomously regulated by hypocotyl and that
      the down-regulation of photosynthesis was not induced by TNC. We conclude that
      the change in the sink activity alters whole-plant growth through the changes in
      both biomass allocation and leaf morphological characteristics in R. sativus. 

PMID- 25997500
TI  - Assessing the accuracy of survey research.

PMID- 25997501
TI  - Interleukin-15 is required for immunosurveillance and immunoprevention of
      HER2/neu-driven mammary carcinogenesis.
AB  - INTRODUCTION: We previously demonstrated that HER2/neu-driven mammary
      carcinogenesis can be prevented by an interleukin-12 (IL-12)-adjuvanted
      allogeneic HER2/neu-expressing cell vaccine. Since IL-12 can induce the release
      of interleukin-15 (IL-15), in the present study we investigated the role played
      by IL-15 in HER2/neu driven mammary carcinogenesis and in its immunoprevention.
      METHODS: HER2/neu transgenic mice with homozygous knockout of IL-15 (here
      referred to as IL15KO/NeuT mice) were compared to IL-15 wild-type HER2/neu
      transgenic mice (NeuT) regarding mammary carcinogenesis, profile of peripheral
      blood lymphocytes and splenocytes and humoral and cellular responses induced by
      the vaccine. RESULTS: IL15KO/NeuT mice showed a significantly earlier mammary
      cancer onset than NeuT mice, with median latency times of 16 and 20 weeks
      respectively, suggesting a role for IL-15 in cancer immunosurveillance. Natural
      killer (NK) and CD8+ lymphocytes were significantly lower in IL15KO/NeuT mice
      compared to mice with wild-type IL-15. The IL-12-adjuvanted allogeneic HER2/neu
      expressing cell vaccine was still able to delay mammary cancer onset but efficacy
      in IL-15-lacking mice vanished earlier: all vaccinated IL15KO/NeuT mice developed
      tumors within 80 weeks of age (median latency of 53 weeks), whereas more than 70
      % of vaccinated NeuT mice remained tumor-free up to 80 weeks of age. Vaccinated
      IL15KO/NeuT mice showed less necrotic tumors with fewer CD3+ lymphocyes and
      lacked perforin-positive infiltrating cells compared to NeuT mice. Concerning the
      anti-vaccine antibody response, antibody titer was unaffected by the lack of IL
      15, but less antibodies of IgM and IgG1 isotypes were found in IL15KO/NeuT mice.
      A lower induction by vaccine of systemic interferon-gamma (IFN-gamma) and
      interleukin-5 (IL-5) was also observed in IL15KO/NeuT mice when compared to NeuT
      mice. Finally, we found a lower level of CD8+ memory cells in the peripheral
      blood of vaccinated IL15KO/NeuT mice compared to NeuT mice. CONCLUSIONS: We
      demonstrated that IL-15 has a role in mammary cancer immunosurveillance and that
      IL-15-regulated NK and CD8+ memory cells play a role in long-lasting
      immunoprevention, further supporting the potential use of IL-15 as adjuvant in
      immunological strategies against tumors.

PMID- 25997502
TI  - Phosphorylation-dependent and Phosphorylation-independent Regulation of
      Helicobacter pylori Acid Acclimation by the ArsRS Two-component System.
AB  - BACKGROUND: The pH-sensitive Helicobacter pylori ArsRS two-component system (TCS)
      aids survival of this neutralophile in the gastric environment by directly
      sensing and responding to environmental acidity. ArsS is required for acid
      induced trafficking of urease and its accessory proteins to the inner membrane,
      allowing rapid, urea-dependent cytoplasmic and periplasmic buffering. Expression
      of ArsR, but not its phosphorylation, is essential for bacterial viability. The
      aim of this study was to characterize the roles of ArsS and ArsR in the response
      of H. pylori to acid. MATERIALS AND METHODS: Wild-type H. pylori and an
      arsR(D52N) phosphorylation-deficient strain were incubated at acidic or neutral
      pH. Gene and protein expression, survival, membrane trafficking of urease
      proteins, urease activity, and internal pH were studied. RESULTS: Phosphorylation
      of ArsR is not required for acid survival. ArsS-driven trafficking of urease
      proteins to the membrane in acid, required for recovery of internal pH, is
      independent of ArsR phosphorylation. ArsR phosphorylation increases expression of
      the urease gene cluster, and the loss of negative feedback in a phosphorylation
      deficient mutant leads to an increase in total urease activity. CONCLUSIONS:
      ArsRS has a dual function in acid acclimation: regulation of urease trafficking
      to UreI at the cytoplasmic membrane, driven by ArsS, and regulation of urease
      gene cluster expression, driven by phosphorylation of ArsR. ArsS and ArsR work
      through phosphorylation-dependent and phosphorylation-independent regulatory
      mechanisms to impact acid acclimation and allow gastric colonization. Furthering
      understanding of the intricacies of acid acclimation will impact the future
      development of targeted, nonantibiotic treatment regimens.

PMID- 25997503
TI  - Central venous catheters: incidence and predictive factors of venous thrombosis.
AB  - AIMS: Central venous catheter access in an acute setting can be a challenge given
      underlying disease and risk for venous thrombosis. Peripherally inserted central
      venous catheters (PICCs) are commonly placed but limit sites for fistula creation
      in patients with chronic renal failure (CKD). The aim of this study is to
      determine the incidence of venous thrombosis from small bore internal jugular
      (SBIJ) and PICC line placement. This investigation identifies populations of
      patients who may not be ideal candidates for a PICC and highlights the importance
      of peripheral vein preservation in patients with renal failure. MATERIALS AND
      METHODS: A venous Doppler ultrasound was performed at the time of SBIJ insertion
      and removal to evaluate for thrombosis in the internal jugular vein. Data was
      collected pre- and post-intervention to ascertain if increased vein preservation
      knowledge amongst the healthcare team led to less use of PICCs. Demographic
      factors were collected in the SBIJ and PICC groups and risk factor analysis was
      completed. RESULTS: 1,122 subjects had PICC placement and 23 had SBIJ placement.
      The incidence of thrombosis in the PICC group was 10%. One patient with an SBIJ
      had evidence of central vein thrombosis when the catheter was removed. Univariate
      and multivariate analysis demonstrated a history of transplant, and the
      indication of total parenteral nutrition was associated with thrombosis
      (p<0.001). The decrease in PICCs placed in patients with CKD 6 months before and
      after intervention was significant (p<0.05). CONCLUSIONS: There are subsets of
      patients ith high risk for thrombosis who may not be ideal candidates for a PICC.

PMID- 25997504
TI  - Safety of add-on tolvaptan in patients with furosemide-resistant congestive heart
      failure complicated by advanced chronic kidney disease: a sub-analysis of a
      pharmacokinetics/ pharmacodynamics study.
AB  - BACKGROUND: Treatment of congestive heart failure (CHF) with loop diuretics, such
      as furosemide, may be associated with complications, including worsening renal
      function and metabolic or electrolyte disturbances. Coadministration of
      tolvaptan, a selective vasopressin V2 receptor antagonist, can ameliorate such
      adverse events by reducing the required dose of loop diuretics; however, the
      safety of tolvaptan in patients with reduced renal function is not known. As a
      result, we conducted an exploratory clinical trial of tolvaptan in 22 patients
      with CHF and advanced chronic kidney disease (CKD). METHODS: We classified these
      patients into three groups according to their estimated glomerular filtration
      rate, namely, CKD stages G3b, G4, and G5. Patients were coadministered tolvaptan
      15 mg once daily for 7 days after single administration of furosemide. We
      assessed patients' hemodynamic parameters, serum chemistry values, and body fluid
      status during the study. RESULTS: On day 8, serum sodium and potassium
      concentrations were significantly higher than baseline values in the G3b
      (p=0.020) and G5 groups (p=0.037), respectively. Although serum urea nitrogen and
      creatinine concentrations increased significantly in the G4 group (p=0.017 and
      p=0.012, respectively), no patient in any of the three groups showed decreased
      renal function on days 2 and 3. In addition, no significant changes in serum uric
      acid, blood pressure, or heart rate were observed in any patient in this study.
      CONCLUSION: In this short-term pilot study, coadministration of tolvaptan and
      furosemide appears to be safe in patients with heart failure and CKD.

PMID- 25997505
TI  - A rare case of peritoneal dialysis-related peritonitis caused by goldfish water
      tankderived Aeromonas hydrophila.
AB  - CASE PRESENTATION: A 62-year-old man was diagnosed with peritoneal dialysis (PD)
      related peritonitis following diarrhea and determination of a dialysate leukocyte
      count of 10,224/MUL. We cultured peritoneal effluent and started intraperitoneal
      antibiotic therapy. Peritonitis immediately improved. Peritoneal effluent culture
      yielded Aeromonas hydrophila. The medical interview revealed that the patient
      kept goldfish as pets. We suspected that the fish tank water was the source of
      the infection, considering the association of A. hydrophila with aquatic
      environments. Culturing of tank water confirmed the presence of Aeromonas.
      Furthermore, we observed that one of the goldfish was suffering from
      lepidorthosis, which is commonly caused by Aeromonas, and we then confirmed that
      the fish's infection was caused by an aeromonad. CONCLUSION: Aeromonas species
      have rarely been identified as the pathogens in PD-related peritonitis; to our
      knowledge, there hitherto have been no reports identifying the source of this
      organism. We present here the process of this infection as elucidated through
      investigation of the living environment of the patient.

PMID- 25997506
TI  - Anti-PLA2R-associated membranous nephropathy: a review with emphasis on
      diagnostic testing methods.
AB  - The majority of cases of primary membranous nephropathy (MN) are associated with
      auto-antibodies against the podocyte antigen M-type phospholipase A2 receptor
      (PLA2R). This particular subset of MN can be diagnosed by identifying anti-PLA2R
      within patient sera or by detecting PLA2R antigen within glomerular immune
      complexes in renal biopsy tissue. Since the discovery of anti-PLA2R in 2009,
      there has been an abundance of literature regarding PLA2R testing as a tool in
      the diagnosis and management of MN, and these tests are increasingly being
      implemented in clinical practice. However, questions still remain about a variety
      of issues such as PLA2R testing in the setting of presumably secondary MN and the
      significance of PLA2R negative primary MN. The goal of this review is to
      summarize the current PLA2R testing methods and highlight special features of
      anti- PLA2R-associated MN. 

PMID- 25997507
TI  - Effect of aspect ratio on the uptake and toxicity of hydroxylated-multi walled
      carbon nanotubes in the nematode, Caenorhabditis elegans.
AB  - OBJECTIVES: In this study, the effect of tube length and outer diameter (OD) size
      of hydroxylated-multi walled carbon nanotubes (OH-MWCNTs) on their uptake and
      toxicity was investigated in the nematode Caenorhabditis elegans using a
      functional mutant analysis. METHODS: The physicochemical properties of three
      different OH-MWCNTs were characterized. Uptake and toxicity were subsequently
      investigated on C. elegans exposed to MWCNTs with different ODs and tube lengths.
      RESULTS: The results of mutant analysis suggest that ingestion is the main route
      of MWCNTs uptake. We found that OH-MWCNTs with smaller ODs were more toxic than
      those with larger ODs, and OH-MWCNTs with shorter tube lengths were more toxic
      than longer counterparts to C. elegans. CONCLUSIONS: Overall the results suggest
      the aspect ratio affects the toxicity of MWCNTs in C. elegans. Further thorough
      study on the relationship between physicochemical properties and toxicity needs
      to be conducted for more comprehensive understanding of the uptake and toxicity
      of MWCNTs.

PMID- 25997508
TI  - Protoporphyrin IX formation after topical application of methyl aminolaevulinate
      and BF-200 aminolaevulinic acid declines with age.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) is a popular treatment modality in
      dermatology. The effect of PDT in epidermal cells depends on formation of
      protoporphyrin IX (PpIX) from 5-aminolevulinic acid (ALA). A variety of
      physiological changes in epidermal function occur with increasing age, but no
      studies have investigated whether PpIX formation is age-related. OBJECTIVES: To
      investigate a possible relationship between age and PpIX formation. METHODS:
      Methyl aminolaevulinate cream (MAL) and 5-ALA gel (BF-200 ALA) were applied to
      two identical fields on the forearm of 30 healthy volunteers for 24 h. The
      volunteers were divided into two age groups: a young group under 55 years (range
      18-54) and an older group over 55 years (range 65-85). PpIX formation was
      measured noninvasively every hour from 1-5 h, and after 18, 21 and 24 h. Skin
      phototype, stratum corneum hydration and ultraviolet (UV) damage were also
      assessed. Treatment efficacy in relation to age was evaluated in 100 basal cell
      carcinomas (BCCs) treated with MAL-PDT. RESULTS: Both photosensitizers induced
      significantly more PpIX formation in the younger group. Linear regression
      revealed a significant age-related decline in PpIX formation after the standard
      application time of 3 h (P < 0.001 for both treatments). Skin phototype, stratum
      corneum hydration and UV damage were not associated with PpIX formation. The
      treatment efficacy of BCCs 3 months after MAL-PDT was higher in young patients (P
      =  0.012). CONCLUSIONS: PpIX formation in human skin declines with age. No
      explanation could be attributed to skin phototype, stratum corneum hydration or
      UV damage. The consequence might be reduced efficacy of PDT in the elderly.

PMID- 25997509
TI  - Production of knockout mice by DNA microinjection of various CRISPR/Cas9 vectors
      into freeze-thawed fertilized oocytes.
AB  - BACKGROUND: Clustered regulatory interspaced short palindromic repeats
      (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing permits the
      rapid production of genetically engineered mice. To make the most of this
      innovative technology, a streamlined procedure is needed for the robust
      construction of CRISPR/Cas9 vectors, the efficient preparation of mouse oocytes,
      and refined genotyping strategies. Although we previously demonstrated the
      applicability of oocyte cryopreservation technologies and various genotyping
      methods in the production of transcription activator-like effector nuclease
      mediated genome editing in mice, it has not yet been clarified whether these
      techniques can be applied to the CRISPR/Cas9-mediated generation of knockout
      mice. In this study, we investigated easy, efficient, and robust methods of
      creating knockout mice using several CRISPR/Cas9 systems. RESULTS: We constructed
      three types of CRISPR/Cas9 vectors expressing: 1) single guide RNA (gRNA) and
      Cas9 nuclease, 2) two gRNAs and Cas9 nickase, and 3) two gRNAs and FokI-dCas9,
      targeting the same genomic locus. These vectors were directly microinjected into
      the pronucleus of freeze-thawed fertilized oocytes, and surviving oocytes were
      transferred to pseudopregnant ICR mice. Cas9 nuclease resulted in the highest
      mutation rates with the lowest birth rates, while Cas9 nickase resulted in the
      highest birth rates with the lowest mutation rates. FokI-dCas9 presented well
      balanced mutation and birth rates. Furthermore, we constructed a single all-in
      one FokI-dCas9 vector targeting two different genomic loci, and validated its
      efficacy by blastocyst analysis, resulting in highly efficient simultaneous
      targeted mutagenesis. CONCLUSIONS: Our report offers several choices of
      researcher-friendly consolidated procedures for making CRISPR/Cas9-mediated
      knockout mice, with sophisticated construction systems for various types of
      CRISPR vectors, convenient preparation of in vitro fertilized or mated freeze
      thawed oocytes, and an efficient method of mutant screening.

PMID- 25997510
TI  - Risk assessments for chronic exposure of children and prospective parents to
      ethylbenzene (CAS No. 100-41-4).
AB  - Potential chronic health risks for children and prospective parents exposed to
      ethylbenzene were evaluated in response to the Voluntary Children's Chemical
      Evaluation Program. Ethylbenzene exposure was found to be predominately via
      inhalation with recent data demonstrating continuing decreases in releases and
      both outdoor and indoor concentrations over the past several decades. The
      proportion of ethylbenzene in ambient air that is attributable to the
      ethylbenzene/styrene chain of commerce appears to be relatively very small, less
      than 0.1% based on recent relative emission estimates. Toxicity reference values
      were derived from the available data, with physiologically based pharmacokinetic
      models and benchmark dose methods used to assess dose-response relationships. An
      inhalation non-cancer reference concentration or RfC of 0.3 parts per million
      (ppm) was derived based on ototoxicity. Similarly, an oral non-cancer reference
      dose or RfD of 0.5 mg/kg body weight/day was derived based on liver effects. For
      the cancer assessment, emphasis was placed upon mode of action information. Three
      of four rodent tumor types were determined not to be relevant to human health. A
      cancer reference value of 0.48 ppm was derived based on mouse lung tumors. The
      risk characterization for ethylbenzene indicated that even the most highly
      exposed children and prospective parents are not at risk for non-cancer or cancer
      effects of ethylbenzene. 

PMID- 25997511
TI  - Searching new signals for production traits through gene-based association
      analysis in three Italian cattle breeds.
AB  - Genome-wide association studies (GWAS) have been widely applied to disentangle
      the genetic basis of complex traits. In cattle breeds, classical GWAS approaches
      with medium-density marker panels are far from conclusive, especially for complex
      traits. This is due to the intrinsic limitations of GWAS and the assumptions that
      are made to step from the association signals to the functional variations. Here,
      we applied a gene-based strategy to prioritize genotype-phenotype associations
      found for milk production and quality traits with classical approaches in three
      Italian dairy cattle breeds with different sample sizes (Italian Brown n = 745;
      Italian Holstein n = 2058; Italian Simmental n = 477). Although classical
      regression on single markers revealed only a single genome-wide significant
      genotype-phenotype association, for Italian Holstein, the gene-based approach
      identified specific genes in each breed that are associated with milk physiology
      and mammary gland development. As no standard method has yet been established to
      step from variation to functional units (i.e., genes), the strategy proposed here
      may contribute to revealing new genes that play significant roles in complex
      traits, such as those investigated here, amplifying low association signals using
      a gene-centric approach.

PMID- 25997512
TI  - Estimation of nitrogen and phosphorus flows in livestock production in Dianchi
      Lake basin, China.
AB  - We assessed the nitrogen (N) and phosphorus (P) flows in intensified livestock
      production systems by investigating nutrient budgets and cycling in the basin of
      Dianchi Lake, one of the most eutrophic lakes in China. We conducted field
      surveys based on feed samplings and interviews of livestock farmers. The N and P
      in local and external feeds, animal body retentions, animal products and
      excretions were calculated at the individual level for dairy cattle, fattening
      pigs, breeding sows, broilers and laying hens. The N and P flows in the total
      livestock production system in the area were estimated by multiplying the
      individual N and P budgets by the number of animals. For the dairy and fattening
      pig productions, N and P supplied from local crops or by-products accounted for
      large parts of the inputs. For the other livestock categories, most of the N and
      P inputs depended on external resources. The N and P outputs through animal
      manure into the cropland were 287 and 66 kg/ha/year, respectively, which were
      higher than the N and P inputs into the livestock production systems from the
      cropland. The N and P loads from manure should be reduced for the establishment
      of sustainable agricultural production systems. 

PMID- 25997513
TI  - Knowledge of physical activity recommendations in adults employed in England:
      associations with individual and workplace-related predictors.
AB  - BACKGROUND: Physical activity guidelines state that adults should engage in at
      least 150 min of moderate to vigorous physical activity (MVPA) per week to
      benefit health. A high proportion of adults in England fail to reach this target.
      Accurate knowledge of MVPA guidelines could influence the amount and quality of
      MVPA engaged in by adults. This study aimed to determine knowledge of the MVPA
      guideline within a large sample of working adults in England and identify
      individual and workplace-related predictors of knowledge. METHODS: 10,992 adults
      completed an online survey which included questions on demographics, knowledge of
      the MVPA guideline and workplace predictors for physical activity. Multinomial
      logistic regression identified predictors of underestimating, overestimating or
      not knowing the MVPA guideline relative to accurately reporting the guideline for
      males and females separately. RESULTS: Respondents were 37% male, 95% White, 63%
      with a degree or higher, and had a mean age of 38.9 +/- 11 years. The MVPA
      guideline was accurately reported by 15% of adults while 13.8% overestimated,
      8.9% underestimated and 62.3% failed to provide any estimate of the guideline.
      Low education predicted underestimation (females: OR = 0.36, 95% CI 0.17, 0.80)
      and not knowing (males: OR = 0.37, 95% CI 0.14, 0.96; females: OR = 0.36, 95% CI
      0.19, 0.69). Ethnicity was a significant predictor for females only (OR 3.55, 95%
      CI 1.46, 8.63; OR 4.03, 95% CI 1.58, 10.27; OR 3.73, 95% CI 1.67, 8.33). Employer
      support for physical activity was a significant predictor of accurate knowledge
      of the MVPA guideline for both males (underestimation: OR = 0.63, 95% CI 0.40,
      1.00; 'don't know': OR = 0.71, 95% CI 0.51, 1.00) and females (overestimation: OR
      = 0.72, 95% CI 0.53, 0.97; underestimation: OR = 0.66, 95% CI 0.47, 0.92; 'don't
      know': OR = 0.60, 95% CI 0.47, 0.76). CONCLUSIONS: Knowledge of the MVPA
      guideline within working adults in England is low. Employers should play a role
      in using targeted strategies to increase knowledge as employer support-related
      factors may influence knowledge of the MVPA guideline. Employers who assert
      strategies to promote physical activity and encourage employees who have
      responsibility for promoting health to educate their colleagues may help improve
      the MVPA knowledge of their employees.

PMID- 25997514
TI  - Palladium-catalyzed regioselective decarboxylative alkylation of arenes and
      heteroarenes with aliphatic carboxylic acids.
AB  - An unprecedented Pd(OAc)2-catalyzed decarboxylative alkylation of unactivated
      arenes, with aliphatic carboxylic acids as inexpensive alkyl sources, is
      reported. The alkylation, controlled by the directing group, is regioselective,
      shows high functional group tolerance, and provides mild access to alkylated
      indolines, 2-phenylpyridines, and azobenzenes under solvent-free conditions in
      moderate to high yields. 

PMID- 25997515
TI  - Molecular patterns of subclinical and clinical rejection of kidney allograft:
      quantity matters.
AB  - BACKGROUND/AIMS: Subclinical rejection diagnosed from protocol biopsies is
      thought to be a risk factor of long- term allograft dysfunction. The reason why
      in some patients subclinical rejection does not represent risk for progression is
      not fully understood. METHODS: The intragraft expression of 376 target genes
      involved in chemokine defense, apoptosis, inflammation, tolerance and TGF-beta
      signalling pathways was measured using quantitative real-time RT-PCR (2(-)??(Ct))
      method in subclinical inflammation (SCI, n=10), clinical inflammation in acute T
      cell mediated rejection (CI, n=10) and no rejection samples (n=9). RESULTS:
      Clinical inflammation group showed a increased expression of genes for chemotaxis
      mediating cytokines (CCL1, CCL17, CCL24, CCL25, CCL26), cytokine receptors (CCR1,
      CCRL2, IL1RAPL2, CXCR5), proinflammatory cytokines (IL12A, LTA), inflammatory
      mediator (PTAFR), complement protein C3, executioner protein of apoptosis
      (CASP7), growth factor (TGFA), colony stimulating factor (CSF-2), proteins
      involved in dendritic cells differentiation and interaction (CD209, LAMP3),
      regulation of immune response (LILRB2, LILBRB4). The quantitative difference in
      transcripts signature between SCI and CI is consistent with stronger
      proinflammatory setting of CI. Prostaglandin E2 receptor gene expression was
      independently associated with lower risk of further graft function deterioration
      (OR 0.11, CI 0.01-0.78, p<0.0001). CONCLUSION: Subclinical acute kidney
      inflammation has transcriptional profile of immune injury of lower extend
      compared to clinical acute inflammation.

PMID- 25997516
TI  - Biologically active [Pd2L4](4+) quadruply-stranded helicates: stability and
      cytotoxicity.
AB  - There is emerging interest in the anti-proliferative effects of
      metallosupramolecular systems due to the different size and shape of these
      metallo-architectures compared to traditional small molecule drugs. Palladium(II)
      containing systems are the most abundant class of metallosupramolecular
      complexes, yet their biological activity has hardly been examined. Here a small
      series of [Pd2(L)4](BF4)4 quadruply-stranded, dipalladium(II) architectures were
      screened for their cytotoxic effects against three cancer cell lines and one non
      malignant line. The helicates exhibited a range of cytotoxic properties, with the
      most cytotoxic complex [Pd2(hextrz)4](BF4)4 possessing low micromolar IC50 values
      against all of the cell lines tested, while the other helicates displayed
      moderate or no cytotoxicity. Against the MDA-MB-231 cell line, which is resistant
      to platinum-based drugs, [Pd2(hextrz)4](BF4)4 was 7-fold more active than
      cisplatin. Preliminary mechanistic studies indicate that the [Pd2(hextrz)4](BF4)4
      helicate does not induce cell death in the same way as clinically used metal
      complexes such as cisplatin. Rather than interacting with DNA, the helicate
      appears to disrupt the cell membrane. These studies represent the first
      biological characterisation of quadruply-stranded helicate architectures, and
      provide insight into the design requirements for the development of biologically
      active and stable palladium(II)-containing metallosupramolecular architectures.

PMID- 25997517
TI  - Erythematous nodule on the earlobe in a patient from Iraq.

PMID- 25997518
TI  - Functional Degradable Polymers by Radical Ring-Opening Copolymerization of MDO
      and Vinyl Bromobutanoate: Synthesis, Degradability and Post-Polymerization
      Modification.
AB  - The synthesis of vinyl bromobutanoate (VBr), a new vinyl acetate monomer
      derivative obtained by the palladium-catalyzed vinyl exchange reaction between
      vinyl acetate (VAc) and 4-bromobutyric acid is reported. The homopolymerization
      of this new monomer using the RAFT/MADIX polymerization technique leads to the
      formation of novel well-defined and controlled polymers containing pendent
      bromine functional groups able to be modified via postpolymerization
      modification. Furthermore, the copolymerization of vinyl bromobutanoate with 2
      methylene-1,3-dioxepane (MDO) was also performed to deliver a range of novel
      functional degradable copolymers, poly(MDO-co-VBr). The copolymer composition was
      shown to be able to be tuned to vary the amount of ester repeat units in the
      polymer backbone, and hence determine the degradability, while maintaining a
      control of the final copolymers' molar masses. The addition of functionalities
      via simple postpolymerization modifications such as azidation and the 1,3-dipolar
      cycloaddition of a PEG alkyne to an azide is also reported and proven by (1)H NMR
      spectroscopy, FTIR spectroscopy, and SEC analyses. These studies enable the
      formation of a novel class of hydrophilic functional degradable copolymers using
      versatile radical polymerization methods.

PMID- 25997519
TI  - Fetal Therapy for Isolated Aqueductal Stenosis.
AB  - Aqueductal stenosis (AS) is a form of noncommunicating hydrocephalus, which
      causes increased intracranial pressure secondary to obstruction of the aqueduct
      of Sylvius. Relief of intracranial pressure in the fetus by ventriculoamniotic
      shunting may diminish or even prevent permanent neurologic injury. Shunting was
      attempted in the 1980s but was abandoned due to technical difficulties. Given the
      advances in prenatal diagnosis and fetal intervention over the last 3 decades, we
      believe that an evidence-based reevaluation of the option is timely and
      appropriate. The aim of this review article is to discuss the clinical
      significance of the diagnosis of AS, current management strategies, current
      diagnostic capabilities, new shunt technology, and barriers to progress. Finally,
      we will advance a research agenda that will provide evidence-based management
      recommendations.

PMID- 25997520
TI  - Safety of Proctocolectomy for Ulcerative Colitis Under Elective and Non-Elective
      Circumstances: Preoperative Corticosteroid Treatment Worsens Outcome.
AB  - BACKGROUND/AIMS: Approximately 20% of patients undergoing surgery for ulcerative
      colitis will retain their rectum. A single-stage proctocolectomy could be an
      appropriate procedure in patients who are definitely not candidates for a later
      restorative procedure, but it is generally not advised in acutely ill patients.
      The aim was to investigate the safety of one-stage proctocolectomy under elective
      and non-elective circumstances, with specific reference to identifying possible
      risk factors for postoperative complications. METHODS: A retrospective cohort
      study, including 54 consecutive patients undergoing proctocolectomy for
      ulcerative colitis. Out of these, 27 (50%) were admitted non-electively. RESULTS:
      Postoperative complications were observed in 30 patients (54%). Wound dehiscence,
      wound infection, and impaired perineal wound healing were observed in 10 (18.5%),
      8 (14.8%), and 10 (18.5%) of the patients, respectively. There was no difference
      between elective and non-elective cases. Complications were observed more often
      in patients receiving high-dose corticosteroids (18/26 vs. 12/28; p = 0.06).
      Impaired perineal wound healing and reoperations were observed more often in the
      corticosteroid-treated group (8/26 vs. 2/28; p = 0.04 and 12/26 vs. 1/28; p =
      0.0003). CONCLUSIONS: Proctocolectomy is equally safe under elective and non
      elective situations, but a preoperative treatment with high-dose corticosteroids
      is associated with an increased risk of complications and reoperations.

PMID- 25997521
TI  - Light up ClO(-) in live cells using an aza-coumarin based fluorescent probe with
      fast response and high sensitivity.
AB  - Hypochlorous acid (HClO)/hypochlorite (ClO(-)), one of the reactive oxygen
      species (ROS), is a key microbicidal agent used for natural defense; however,
      HClO is also responsible for some human diseases. Although much effort has been
      made to develop HClO-selective fluorescent probes, many of them display a delayed
      response time and nanomole-sensitive probes are rare. In this study, we designed
      and synthesized an aza-coumarin based fluorescent probe AC-ClO for ClO(-)
      determination with fast response (completed within 2 min) and high sensitivity
      (detection limit is 25 nM). AC-ClO displayed a color change from pink to light
      yellow and a remarkable "turn-on" fluorescence response towards ClO(-). Confocal
      fluorescence microscopy experiments demonstrated that the probe could be applied
      for the live-cell imaging of exogenous and endogenous ClO(-).

PMID- 25997522
TI  - On how much biodiversity is covered in Europe by national protected areas and by
      the Natura 2000 network: insights from terrestrial vertebrates.
AB  - The European Union has made extensive biodiversity conservation efforts with the
      Habitats and Birds Directives and with the establishment of the Natura 2000
      network of protected areas, one of the largest networks of conservation areas
      worldwide. We performed a gap analysis of the entire Natura 2000 system plus
      national protected areas and all terrestrial vertebrates (freshwater fish
      excluded). We also evaluated the level of connectivity of both systems, providing
      therefore a first estimate of the functionality of the Natura 2000 system as an
      effective network of protected areas. Together national protected areas and the
      Natura 2000 network covered more than one-third of the European Union. National
      protected areas did not offer protection to 13 total gap species (i.e., species
      not covered by any protected area) or to almost 300 partial gap species (i.e.,
      species whose representation target is not met). Together the Natura 2000 network
      and national protected areas left 1 total gap species and 121 partial gap species
      unprotected. The terrestrial vertebrates listed in the Habitats and Birds
      Directives were relatively well covered (especially birds), and overall
      connectivity was improved considerably by Natura 2000 sites that act as stepping
      stones between national protected areas. Overall, we found that the Natura 2000
      network represents at continental level an important network of protected areas
      that acts as a good complement to existing national protected areas. However, a
      number of problems remain that are mainly linked to the criteria used to list the
      species in the Habitats and Birds Directives. The European Commission initiated
      in 2014 a process aimed at assessing the importance of the Birds and Habitats
      Directives for biodiversity conservation. Our results contribute to this
      assessment and suggest the system is largely effective for terrestrial
      vertebrates but would benefit from further updating of the species lists and
      field management. 

PMID- 25997523
TI  - Social Status and Arginine Vasotocin Neuronal Phenotypes in a Cichlid Fish.
AB  - The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine
      vasopressin play a key role in the regulation of social behaviour across
      vertebrates. In teleost fishes, three AVT neuronal populations have been
      described in the preoptic area (POA): the parvocellular (pPOA), the magnocellular
      (mPOA) and the gigantocellular (gPOA). Neurons from each of these areas project
      both to the pituitary and to other brain regions, where AVT is supposed to
      regulate neural circuits underlying social behaviour. However, in the fish
      species studied so far, there is considerable variation in which AVT neuronal
      populations are involved in behavioural modulation and in the direction of the
      effect. In this study, the association between AVT neuronal phenotypes and social
      status was investigated in the Mozambique tilapia (Oreochromis mossambicus). This
      species is an African female mouth-brooding cichlid fish in which males form
      breeding aggregations in which dominant males establish territories and
      subordinate males to act as floaters. With respect to sex differences in AVT
      neuronal phenotypes, females have a larger number of AVT neurons in the pPOA and
      mPOA. Within males, AVT appeared associated with social subordination, as
      indicated by the larger cell body areas of AVT neurons in mPOA and gPOA nuclei of
      non-territorial males. There were also positive correlations between submissive
      behaviour and the soma size of AVT cells in all three nuclei and AVT cell number
      in the mPOA. In summary, the results provide evidence for an involvement of AVT
      in the modulation of social behaviour in tilapia, but it was not possible to
      identify specific roles for specific AVT neuronal populations. The results
      presented here also contrast with those previously published for another cichlid
      species with a similar mating system, which highlights the species-specific
      nature of the pattern of association between AVT and social behaviour even within
      the same taxonomic family.

PMID- 25997524
TI  - Functional neuroimaging studies in asymmetric hearing loss.
AB  - This article presents an analysis of the impact of functional neuroimaging
      studies (positron emission tomography, PET) in asymmetric hearing loss based on
      the clinical expertise obtained from a group of 21 patients. In these patients,
      PET studies are performed at rest and after auditory stimulation in order to
      measure the increase in brain activity in the ipsi- and contralateral cortex,
      providing supporting evidence to recommend a specific treatment and the side to
      implant. In conclusion, PET is a useful tool for selected cases in which
      information on the metabolic status of the auditory pathway can drive the
      decision regarding the treatment of the most appropriate ear. However, in view of
      our small sample, further research is needed to confirm our results in this
      topic.

PMID- 25997525
TI  - Emergency left colonic resections on an acute surgical unit: does
      subspecialization improve outcomes?
AB  - BACKGROUND: Left-sided colonic pathologies requiring emergency resection are
      commonly encountered on an acute surgical unit. Subspecialist colorectal (CR)
      management of these patients may result in decreased morbidity, mortality and
      stoma rates. This study is the first of its kind comparing outcomes between CR
      surgeons and general surgeons on an acute surgical unit. METHODS: This is a
      retrospective review of 196 consecutive patients who underwent emergency left
      colonic resection on an acute surgical unit between January 2009 and July 2014.
      Patients were divided into two groups dependent on whether their surgery was
      managed by a CR specialist or general surgeon. Primary outcome measures were 30
      day mortality, rate of primary anastomosis and overall stoma rate. RESULTS:
      Patients in the two groups were comparable for age, sex, American Society for
      Anesthesiologists score as well as CR POSSUM scores. Rates of primary anastomosis
      were significantly higher in the CR group compared with the acute surgical unit
      group (85.5 versus 28.7%, P <= 0.001). Overall stoma rates were significantly
      lower in the CR group (40.4 versus 88.8%, P = 0.0001). Thirty-day mortality was
      similar in both groups. Other secondary markers of morbidity including length of
      stay, return to theatre, anastomotic leak rate, wound problems and systemic
      complications had no significant difference between the two groups. CONCLUSION:
      Subspecialist CR management of patients undergoing emergency left-sided colonic
      resection on an acute surgical unit is associated with a similar level of
      morbidity and mortality while safely achieving significantly higher rates of
      primary anastomosis and lower stoma rates.

PMID- 25997526
TI  - Antinociceptive Efficacy of Retigabine in the Monosodium Lodoacetate Rat Model
      for Osteoarthritis Pain.
AB  - BACKGROUND: The goal of pharmacological osteoarthritis (OA) treatments is to
      reduce pain and thus increase patient joint function and quality of life.
      Retigabine, a potent Kv7/M channel activator, shows analgesic efficacy in animal
      models of chronic inflammatory and neuropathic pain. We hypothesized that
      retigabine may also mitigate OA pain. To determine the effects of retigabine on
      pain behavior associated with monosodium iodoacetate (MIA)-induced OA. METHODS:
      The OA model was established with an intra-articular injection of MIA through the
      right patellar ligament, animals were treated with retigabine, and pain-related
      behaviors were assessed. RESULTS: Retigabine significantly increased the
      mechanical threshold and prolonged the withdrawal latency of OA rats at 3-14
      days. Retigabine also increased the mechanical threshold and prolonged the
      withdrawal latency of OA pain in a dose-dependent manner, with the strongest
      antinociceptive effect occurring at 60 min. The antinociceptive effects of
      retigabine were fully antagonized by the Kv7/M channel blocker XE991. CONCLUSION:
      Retigabine showed antinociceptive effects for OA pain in the MIA model at
      different times during pain development. Retigabine may be an alternative
      therapeutic treatment for OA.

PMID- 25997527
TI  - Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord
      Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia.
AB  - BACKGROUND: Fetal macrosomia and its associated complications are the most
      frequent and serious morbidities for infants associated with gestational diabetes
      mellitus (GDM). The associations between long non-coding RNAs (lncRNAs) and
      macrosomia have been rarely reported; therefore, we investigated the umbilical
      cord lncRNA profiles in GDM macrosomia. METHOD: Thirty pairs of GDM macrosomia
      and normal controls were divided into three subgroups randomly, and the umbilical
      cord vein blood from each subgroup was mixed, and hybridized to a microarray
      containing probes representing 33,000 lncRNA genes. Quantitative real-time
      polymerase chain reaction (qPCR) was used to validate selected differentially
      expressed lncRNAs. The gene ontology (GO), pathway and network analysis were
      performed. RESULT: The microarray identified 8814 lncRNAs that were expressed in
      the umbilical cord blood, of which 349 were significantly upregulated and 892
      were significantly downregulated (fold-change >= 2.0) in GDM group. The highest
      enriched GOs targeted by downregulated transcripts were biological regulation.
      Pathway analysis indicated that nine pathways corresponded to downregulated
      transcripts. CONCLUSIONS: Certain lncRNAs that were aberrantly expressed in the
      umbilical cord blood from GDM macrosomia might play a partial or key role in GDM
      macrosomia development. This study provided potential targets for treatment of
      macrosomia and novel insights into macrosomia biology.

PMID- 25997529
TI  - Opinion paper: prospects for the fed-aquaculture sector.

PMID- 25997528
TI  - Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for adults
      with swallowing disturbances.
AB  - BACKGROUND: A number of conditions compromise the passage of food along the
      digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven
      technique, although its prolonged use can lead to complications such as lesions
      to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration
      pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG),
      is generally used when there is a need for enteral nutrition for a longer time
      period. There is a high demand for PEG in patients with swallowing disorders,
      although there is no consistent evidence about its effectiveness and safety as
      compared to NGT. OBJECTIVES: To evaluate the effectiveness and safety of PEG
      compared with NGT for adults with swallowing disturbances. SEARCH METHODS: We
      searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to
      January 2014, and contacted the main authors in the subject area. There was no
      language restriction in the search. SELECTION CRITERIA: We planned to include
      randomised controlled trials comparing PEG versus NGT for adults with swallowing
      disturbances or dysphagia and indications for nutritional support, with any
      underlying diseases. The primary outcome was intervention failure (e.g. feeding
      interruption, blocking or leakage of the tube, no adherence to treatment). DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
      The Cochrane Collaboration. For dichotomous and continuous variables, we used
      risk ratio (RR) and mean difference (MD), respectively with the random-effects
      statistical model and 95% confidence interval (CI). We assumed statistical
      heterogeneity when I2 > 50%. MAIN RESULTS: We included 11 randomised controlled
      studies with 735 participants which produced 16 meta-analyses of outcome data.
      Meta-analysis indicated that the primary outcome of intervention failure,
      occurred in lower proportion of participants with PEG compared to NGT (RR 0.18,
      95% CI 0.05 to 0.59, eight studies, 408 participants, low quality evidence) and
      this difference was statistically significant. For this outcome, we also
      subgrouped the studies by endoscopic gastrostomy technique into pull, and push
      and not reported. We observed a significant difference favouring PEG in the pull
      subgroup (RR 0.07, 95% CI 0.01 to 0.35, three studies, 90 participants). Thepush
      subgroup contained only one clinical trial and the result favoured PEG (RR 0.05,
      95% CI 0.00 to 0.74, one study, 33 participants) techniques. We found no
      statistically significant difference in cases where the technique was not
      reported (RR 0.43, 95% CI 0.13 to 1.44, four studies, 285 participants).There was
      no statistically significant difference between the groups for meta-analyses of
      the secondary outcomes of mortality (RR 0.86, 95% CI 0.58 to 1.28, 644
      participants, nine studies, very low quality evidence), overall reports of any
      adverse event at any follow-up time point (ITT analysis, RR 0.83, 95% CI 0.51 to
      1.34), 597 participants, 6 studies, moderate quality evidence), specific adverse
      events including pneumonia (aspiration) (RR 0.70, 95% CI 0.46 to 1.06, 645
      participants, seven studies, low quality evidence), or for the meta- analyses of
      the secondary outcome of nutritional status including weight change from
      baseline, and mid-arm circumference at endpoint, although there was evidence in
      favour of PEG for meta-analyses of mid-arm circumference change from baseline (MD
      1.16, 95% CI 1.01 to 1.31, 115 participants, two studies), and levels of serum
      albumin were higher in the PEG group (MD 6.03, 95% CI 2.31 to 9.74, 107
      participants).For meta-analyses of the secondary outcomes of time on enteral
      nutrition, there was no statistically significant difference (MD 14.48, 95% CI 
      2.74 to 31.71; 119 participants, two studies). For meta-analyses of quality of
      life measures (EuroQol) outcomes in two studies with 133 participants, for
      inconvenience (RR 0.03, 95% CI 0.00 to 0.29), discomfort (RR 0.03, 95% CI 0.00 to
      0.29), altered body image (RR 0.01, 95% CI 0.00 to 0.18; P = 0.001) and social
      activities (RR 0.01, 95% CI 0.00 to 0.18) the intervention favoured PEG, that is,
      fewer participants found the intervention of PEG to be inconvenient,
      uncomfortable or interfered with social activities. However, there were no
      significant differences between the groups for pain, ease of learning to use, or
      the secondary outcome of length of hospital stay (two studies, 381 participants).
      AUTHORS' CONCLUSIONS: PEG was associated with a lower probability of intervention
      failure, suggesting the endoscopic procedure may be more effective and safe
      compared with NGT. There is no significant difference in mortality rates between
      comparison groups, or in adverse events, including pneumonia related to
      aspiration. Future studies should include details of participant demographics
      including underlying disease, age and gender, and the gastrostomy technique.

PMID- 25997530
TI  - Hair cortisol detection in dairy cattle by using EIA: protocol validation and
      correlation with faecal cortisol metabolites.
AB  - Hair may be a useful matrix to detect cumulative cortisol concentrations in
      studies of animal welfare and chronic stress. The aim of this study was to
      validate a protocol for cortisol detection in hair from dairy cattle by enzyme
      immunoassay (EIA). Seventeen adult Holstein-Friesian dairy cows were used during
      the milking period. Hair cortisol concentration was assessed in 25-day-old hair
      samples taken from the frontal region of the head, analysing black and white
      coloured hair separately. Concentrations of cortisol metabolites were determined
      in faeces collected twice a week during the same period of time. There was a high
      correlation between cortisol values in faeces and cortisol in white colour hair
      samples but such correlation was not significant with the black colour hair
      samples. The intra- and inter-assay coefficients of variation were 4.9% and
      10.6%, respectively. The linearity showed R 2=0.98 and mean percentage error of 
      10.8 +/- 1.55%. The extraction efficiency was 89.0 +/- 23.52% and the parallelism
      test showed similar slopes. Cortisol detection in hair by using EIA seems to be a
      valid method to represent long-term circulating cortisol levels in dairy cattle.

PMID- 25997531
TI  - Supplementation of Rosemary extract in the diet of Nero Siciliano pigs:
      evaluation of the antioxidant properties on meat quality.
AB  - In the present study, the effect of Rosmarinus officinalis L. dietary
      supplementation on meat quality and oxidative stability of Nero Siciliano pigs
      was examined. During the growing-fattening period, 32 Nero Siciliano pigs were
      allotted into two treatment groups consisting of 8 replicates with 2 pigs per
      pen. For 90 days, the animals received a basal diet: one group (CTR) was not
      dietary supplemented, whereas the other group received (1 g/kg) rosemary extract
      (ROX). Supplementation with rosemary extract significantly improved the
      polyunsaturated fatty acid content of the meat, which showed higher values in the
      meat of the ROX group compared with the CTR group (P0.05). Color measurement
      performed in the present study on meat samples from the two dietary treatments
      showed that redness decreased (P=0.046) and hue values increased (P=0.036),
      indicating that a deterioration of the initial color occurred and that the
      rosemary extract was ineffective in preventing color deterioration. Nevertheless,
      the lightness, yellowness and chroma color descriptors showed similar values in
      relation to dietary treatment (P>0.05). Considering the nutritional value of meat
      as an important contributor to the overall quality, the results obtained in this
      study support the possibility of the dietary supplementation with R. officinalis
      L. extract in pigs as a functional additive in livestock feeding. 

PMID- 25997532
TI  - Involvement of NOX in the regulation of renal tubular expression of Na/K-ATPase
      in acute unilateral ureteral obstruction rats.
AB  - BACKGROUND/AIMS: Renal tubular expression of Na/K-ATPase has been reported to be
      rapidly reduced in kidneys after unilateral ureteral obstruction (UUO),
      contributing to compromised sodium regulation. In this study, apocynin was
      utilized to test the hypothesis that the renal nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase (NOX) system is involved in the regulation of Na/K
      ATPase expression in early UUO. METHODS: Eighty Wistar rats underwent UUO or sham
      surgery, and half of each group was administered 100 mg/kg apocynin by oral
      gavage after surgery. Renal tissue samples were collected on day 1 and day 3
      after surgery and the distribution of NOX2, NOX4 and Na/K-ATPase was assessed by
      immunofluorescence and immunohistochemical staining. The Heme oxygenase-1 (HO-1),
      NOX2, NOX4, osteopontin, Na/K-ATPase and aquaporin-1 (AQP-1) content of renal
      homogenates was assessed by immunoblotting, and malondialdehyde (MDA), nitric
      oxide (NO) content was assessed by biochemical analyses. Activity of inducible NO
      synthase (iNOS) and antioxidant enzymes was assessed by enzymatic assay. RESULTS:
      Kidney Na/K-ATPase and AQP-1 content was decreased, and MDA and NOX4, NOX2 and HO
      1 content were increased in the obstructed kidneys of UUO rats. Apocynin
      attenuated these changes and partially, but significantly, reversed the
      downregulation of Na/K-ATPase and AQP-1 in UUO rats. However, apocynin did not
      alter iNOS activity and NO production, osteopontin expression or the activity of
      antioxidant enzymes. CONCLUSION: Activation of the NOX system and subsequent
      production of ROS are likely responsible for the downregulation of renal tubular
      Na/K-ATPase expression in early UUO.

PMID- 25997533
TI  - Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in
      Patients with Coronary Artery Ectasia.
AB  - OBJECTIVES: To assess the prognostic value of coexisting coronary artery disease
      (CAD), Markis class, and ectasia ratio for major adverse cardiovascular events in
      patients with coronary artery ectasia (CAE). METHODS: A total of 512 consecutive
      patients with angiographically proven CAE were enrolled. Coronary ectasia extent
      was graded using the Markis class, and ectasia severity was assessed based on the
      ectasia ratio. Patients were followed up for a median of 34.6 months. RESULTS: In
      the current study, 76 cases had isolated CAE, while the remaining 436 cases had
      coexisting CAD (mixture CAE). Males (84.4%) were predominantly affected, and the
      right coronary artery (55.1%) was most commonly involved. During follow-up, 86
      overall major adverse cardiovascular events were diagnosed. Kaplan-Meier analysis
      failed to reveal any differences between isolated and mixture CAE in both
      cumulative and event-free survival analyses (p=0.429 and p=0.277, respectively).
      Moreover, when patients were divided into 4 groups according to Markis class
      (type I-IV) or 2 groups based on the ectasia ratio (1.5-2.0 and >2.0), there was
      no significant difference in survival outcomes among the groups (p>0.05).
      CONCLUSIONS: In this follow-up study with a relatively large sample, the survival
      rate of patients with CAE appeared to be independent of coexisting CAD and
      ectasia extent and severity.

PMID- 25997534
TI  - Photo-triggered fluorescent theranostic prodrugs as DNA alkylating agents for
      mechlorethamine release and spatiotemporal monitoring.
AB  - We describe a new theranostic strategy for selective delivery and spatiotemporal
      monitoring of mechlorethamine, a DNA alkylating agent. A photo-responsive prodrug
      is designed and composed of a photolabile o-nitrophenylethyl group, a DNA
      alkylating mechlorethamine drug and a coumarin fluorophore. Masking of the "N" in
      mechlorethamine in a positively charged state in the prodrug renders it inactive,
      non-toxic, selective and non-fluorescent. Indeed, the stable prodrug shows
      negligible cytotoxicity towards normal cells with and without UV activation and
      is completely non-fluorescent. However, upon photo-irradiation, the active
      mechlorethamine is released and induces efficient DNA cross-links, accompanied by
      a strong fluorescence enhancement (152 fold). Furthermore, DNA cross-linking
      activity from the release can be transformed into anticancer activity observed in
      in vitro studies of tumor cells. Importantly, the drug release progress and the
      movement can be conveniently monitored by fluorescence spectroscopy. The
      mechanistic study proves that the DNA cross-linking activity is mainly due to the
      release of DNA alkylating mechlorethamine. Altogether, the studies show the power
      of the theranostic strategy for efficient therapy in cancer treatment. 

PMID- 25997535
TI  - Removing inactive NRTIs in a salvage regimen is safe, maintains virological
      suppression and reduces treatment costs: results from the VERITAS study
      (TMC114HIV4054).
AB  - BACKGROUND: Despite the benefit of maintaining inactive Nucleotide/side reverse
      transcriptase inhibitors (NRTIs) in salvage regimens, they are associated with
      increased toxicity and treatment costs. Current evidence suggests that NRTI
      sparing regimens in patients failing ART are non-inferior to NRTI-including
      regimens. This study aimed to evaluate the impact of removing at least one
      inactive NRTI on virologic, safety, and financial outcomes. METHODS: Drug
      resistant, virologically suppressed patients with CD4 >250 cells/ml on a stable
      regimen of four or more antiretrovirals (ARVs) were enrolled in a 48-week
      prospective, open-label pilot trial. One inactive NRTI was removed at baseline.
      Patients taking over five ARVs had a second inactive NRTI removed at 24 weeks.
      Viral load, CD4 count, and adverse events were assessed at baseline, 24, and 48
      weeks. RESULTS: Thirty-one male patients participated. Twenty-nine (94%) patients
      had lamivudine (3TC) or emtricitabine (FTC) removed and four patients had an
      additional NRTI removed. One patient was excluded at week 26 for discontinuing an
      active NRTI. All patients maintained undetectable viral loads at weeks 24 (100%)
      and 48 [PP = 100%; Intent-to-treat (ITT) = 97%]. At 48 weeks, patients had a
      median gain of 20 CD4 (IQR: - 50, +133; mean +39) compared to baseline. Three
      patients exhibited Grade III bilirubin elevation (two Grade II and one Grade III
      at baseline), which returned to baseline levels. No serious adverse events were
      observed. Removal of one or two ARVs equated to a mean annual savings of $3319
      CDN (11%) and $8630 CDN (24%), respectively. CONCLUSION: Removing inactive NRTIs
      in patients with a controlled viral load appears to be safe, maintains
      virological suppression, and reduces treatment costs.

PMID- 25997536
TI  - Human mesenchymal stem cells enhance cancer cell proliferation via IL-6 secretion
      and activation of ERK1/2.
AB  - Human mesenchymal stem cells (hMSC) are frequently used in tissue engineering.
      Due to their strong tumor tropism, hMSC seem to be a promising vehicle for
      anticancer drugs. However, interactions between hMSC and cancer are ambiguous.
      Particularly the cytokines and growth factors seem to play an important role in
      cancer progression and metastasis. The present study evaluated the effects of
      hMSC on head and neck squamous cell carcinoma (HNSCC) cell lines (FaDu and
      HLaC78) in vitro. hMSC released several cytokines and growth factors. FaDu and
      HLaC78 showed a significant enhancement of cell proliferation after cultivation
      with hMSC-conditioned medium as compared to control. This proliferation
      improvement was inhibited by the addition of anti-IL-6. The western blot showed
      an activation of Erk1/2 in FaDu and HLaC78 by hMSC-conditioned medium. HNSCC cell
      lines expressed EGFR. The current study confirms the importance of cytokines
      secreted by hMSC in cancer biology. Especially IL-6 seems to play a key role in
      cancer progression. Thus, the use of hMSC as a carrier for cancer therapy must be
      discussed critically. Future studies should evaluate the possibility of
      generating genetically engineered hMSC with, for example, the absence of IL-6
      secretion.

PMID- 25997537
TI  - Pirfenidone attenuates bladder fibrosis and mitigates deterioration of bladder
      function in a rat model of partial bladder outlet obstruction.
AB  - To investigate the effects of pirfenidone (PFD) on the attenuation of bladder
      remodeling, and the associated functional changes caused by partial bladder
      outlet obstruction (pBOO), the present study performed surgery on adult male
      Sprague-Dawley rats produce a model of pBOO. The rats in the pBOO group were
      administered a placebo and, in the CMC group, PFD mixed with the placebo was
      administered orally at 500 mg/kg body weight each day for 5 weeks, from 1 week
      after surgery. The rat bladders were harvested for biochemical analysis following
      cystometry at the end of the 6 week period. The histopathology was determined
      using Masson's trichrome staining. The mRNA and protein levels of pro-fibrotic
      growth factors and extracellular matrix subtypes were assessed. pBOO debilitated
      bladder function and caused the parameters from cystometry to increase
      significantly compared with those in the control group (P<0.05), which were
      mitigated significantly following PFD treatment (P<0.05). In terms of the
      histology, the rats in the pBOO group exhibited significant increases in bladder
      weight, muscle hypertrophy and deposition of collagens, which were suppressed by
      PFD treatment (P<0.05). Based on the biochemical analysis, significant increases
      in the mRNA levels of collagen subtypes and growth factors, and protein levels of
      profibrotic growth factors and alpha-smooth muscle actin in the bladders of rats
      in the pBOO group were reduced following PFD treatment. PFD prevented bladder
      remodeling and attenuated bladder fibrosis and, therefore, mitigated the
      deterioration of bladder function during the initial stage of pBOO.

PMID- 25997538
TI  - Umbelliferone exhibits anticancer activity via the induction of apoptosis and
      cell cycle arrest in HepG2 hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is a highly malignant tumor, associated with poor
      patient prognoses, and high rates of morbidity and mortality. To date, the
      therapeutic strategies available for the treatment of HCC remain limited. The
      present study aimed to elucidate the anticancer activity of umbelliferone, a
      naturally occurring coumarin derivative isolated from Ferula communis, against
      the HepG2 HCC cell line. A 3-(4,5-dimthylthaizol-2-yl)-2,5, diphenyltetrazolium
      bromide assay was used to evaluate cell viability following umbelliferone
      treatment, and the effects of umbelliferone on cell cycle progression and
      apoptosis were evaluated using flow cytometry. The presence of morphological
      features characteristic of apoptosis, including cell shrinkage, membrane
      blebbing, nuclear condensation and apoptotic body formation, were evaluated in
      HepG2 cells following umbelliferone treatment. Cell cycle analysis conducted via
      propidium iodide (PI) staining indicated that umbelliferone treatment induced
      cell cycle arrest at S phase in HepG2 cells. Analysis with Annexin V and PI
      staining revealed that umbelliferone induced apoptotic events in HepG2 cells in a
      concentration-dependant manner (0-50 uM). Umbelliferone also induced dose
      dependant DNA fragmentation. In conclusion, umbelliferone was found to exhibit
      significant anticancer effects via the induction of apoptosis, cell cycle arrest
      and DNA fragmentation in HepG2 cancer cells.

PMID- 25997539
TI  - SOCIAL, HISTORICAL AND CULTURAL DIMENSIONS OF TUBERCULOSIS.
AB  - Tuberculosis (TB) researchers and clinicians, by virtue of the social disease
      they study, are drawn into an engagement with ways of understanding illness that
      extend beyond the strictly biomedical model. Primers on social science concepts
      directly relevant to TB, however, are lacking. The particularities of TB disease
      mean that certain social science concepts are more relevant than others. Concepts
      such as structural violence can seem complicated and off-putting. Other concepts,
      such as gender, can seem so familiar that they are left relatively unexplored. An
      intimate familiarity with the social dimensions of disease is valuable,
      particularly for infectious diseases, because the social model is an important
      complement to the biomedical model. This review article offers an important
      introduction to a selection of concepts directly relevant to TB from health
      sociology, medical anthropology and social cognitive theory. The article has
      pedagogical utility and also serves as a useful refresher for those researchers
      already engaged in this genre of work. The conceptual tools of health sociology,
      medical anthropology and social cognitive theory offer insightful ways to examine
      the social, historical and cultural dimensions of public health. By recognizing
      cultural experience as a central force shaping human interactions with the world,
      TB researchers and clinicians develop a more nuanced consideration of how health,
      illness and medical treatment are understood, interpreted and confronted. 

PMID- 25997540
TI  - AMD3100 reduces CXCR4-mediated survival and metastasis of osteosarcoma by
      inhibiting JNK and Akt, but not p38 or Erk1/2, pathways in in vitro and mouse
      experiments.
AB  - Osteosarcoma (OS) has an unfavorable prognosis and tends to metastasize to lung
      tissue. Although the CXCL12-CXCR4 axis appears to affect progression and
      metastasis in numerous tumors, its mechanism and downstream pathways in OS remain
      unclear. We used western blotting and flow cytometry to detect CXCR4 and CXCR7
      expression in two OS cell lines (LM8 and Dunn). An MTT assay was used to evaluate
      the effects of CXCL12 and AMD3100, a specific CXCR4 antagonist, on cell
      viability. Flow cytometry was utilized to analyze changes in apoptosis induced by
      serum deprivation following treatment with CXCL12 and AMD3100. A Transwell assay
      was used to assess cell migration in response to CXCL12 and AMD3100. Western
      blotting was performed to identify the phosphorylation of signaling molecules
      (JNK, c-Jun, Akt, p38 and Erk1/2) and expression of caspase-3 and -8, and PARP.
      Mouse models were employed to evaluate AMD3100 inhibition of primary OS growth
      and lung metastasis in vivo. CXCR4 expression was detected in LM8 but not Dunn
      cells, and neither cell line expressed CXCR7. The addition of CXCL12 induced the
      survival and migration of serum-starved CXCR4+ LM8 cells activating JNK and Akt
      pathways, which were abrogated by adding AMD3100. However, similar results were
      not observed in CXCR4- Dunn cells. CXCL12 protected LM8, but not Dunn cells, from
      apoptosis induced by serum deprivation by suppressing PARP cleavage, which was
      partly reversed by AMD3100. In a mouse model, AMD3100 reduced primary tumor
      growth and lung metastasis compared with the controls. Thus, the CXCL12-CXCR4
      axis regulated OS survival and metastasis through the JNK and Akt pathways, and
      blocking them with AMD3100 was found to be a potential OS treatment.

PMID- 25997542
TI  - Clinical Features of Community-Acquired Helicobacter cinaedi Bacteremia.
AB  - BACKGROUND: There are growing numbers of reports concerning the clinical and
      pathological features of Helicobacter cinaedi (H. cinaedi) bacteremia; however,
      few reports have discussed the features of this condition in healthy individuals.
      PATIENTS AND METHODS: A retrospective observational study was conducted at a
      Japanese tertiary care hospital to assess the clinical features of community
      acquired H. cinaedi. All patients in whom H. cinaedi was isolated between January
      2009 and March 2014 were identified from the hospital database. RESULTS: Of the
      28 patients included in the study, 12 had community-acquired H. cinaedi
      bacteremia. The most common clinical feature was cellulitis (n = 17). However,
      nearly half of the patients with healthcare-associated or nosocomial-associated
      bacteremia displayed no symptoms with the exception of fever. Most patients were
      successfully treated with a 14-day regime of third-generation cephalosporins or
      tetracycline. CONCLUSIONS: Our results show that H. cinaedi infections are quite
      common in immunocompetent community-dwelling individuals.

PMID- 25997541
TI  - The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for
      functional studies.
AB  - BACKGROUND: Urothelial bladder cancer is a highly heterogeneous disease. Cancer
      cell lines are useful tools for its study. This is a comprehensive genomic
      characterization of 40 urothelial bladder carcinoma (UBC) cell lines including
      information on origin, mutation status of genes implicated in bladder cancer
      (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high
      density SNP arrays, uniparental disomy (UPD) events, and gene expression.
      RESULTS: Based on gene mutation patterns and genomic changes we identify lines
      representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor
      suppressor-driven pathway. High-density array copy number analysis identified
      significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e.
      6p22.1) in regions altered in tumors but not previously described as affected in
      bladder cell lines. We also identify new evidence for frequent regions of UPD,
      often coinciding with regions reported to be lost in tumors. Previously
      undescribed chromosome X losses found in UBC lines also point to potential tumor
      suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a
      lower number of UPD events. CONCLUSIONS: Overall, there is a predominance of more
      aggressive tumor subtypes among the cell lines. We provide a cell line
      classification that establishes their relatedness to the major molecularly
      defined bladder tumor subtypes. The compiled information should serve as a useful
      reference to the bladder cancer research community and should help to select cell
      lines appropriate for the functional analysis of bladder cancer genes, for
      example those being identified through massive parallel sequencing.

PMID- 25997544
TI  - Comparison of pharmacokinetics and uric acid lowering effect between two
      different strength febuxostat formulations (80 mg vs. 40 mg) in healthy subjects.
AB  - OBJECTIVE: Febuxostat is a selective inhibitor of xanthine oxidase, which is used
      to manage hyperuricemia in patients with gout. The objective of the study was to
      compare the pharmacokinetics of two different strength of febuxostat formulations
      (80 mg and 40 mg). METHODS: A randomized, single-dose, open-label, two-period,
      two-sequence crossover study with a 7-day washout period was conducted in 30
      healthy male subjects. Participants received either reference (1 ? 80 mg) or test
      (2 ? 40 mg) formulations during the first period and the alternative formulation
      during the second period. Plasma samples for the drug analysis were collected up
      to 24 hours after treatment. RESULTS: All pharmacokinetic parameters were
      comparable between the two formulations The observed mean Cmax, AUC(last), and
      AUC(infinity) values for the reference formulation were 3,670 ng/mL, 12,086 ng x
      h/mL, and 12,880 ng x h/mL, respectively. Corresponding values for the test
      formulation were 4,108 ng/mL, 12,689 ng x h/mL, and 13,278 ng x h/mL,
      respectively. The geometric mean ratios (90% CI) between the two formulations
      were 1.1273 (1.0286 - 1.2355) for Cmax, 1.054 (1.0115 - 1.0980) for AUC(last),
      and 1.0395 (0.9959 - 1.0851) for AUC(infinity). The changes of serum uric acid at
      24 hours after reference and test formations were comparable (-1.36 mg/dL for
      reference and -1.37 mg/dL for test; p = 0.892). CONCLUSION: The results of the
      present study indicated that the reference and test formulations have comparable
      pharmacokinetics and that these two formulations meet the regulatory criteria for
      bioequivalence. In addition, the reduction of serum UA levels in the reference
      formulation was similar to that of the test formulation after a single dose.

PMID- 25997546
TI  - WITHDRAWN: XB130 expression in human osteosarcoma: a clinical and experimental
      study.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 25997545
TI  - Current smoking is an independent risk factor for new-onset diabetes mellitus
      during highdose glucocorticoid treatment.
AB  - AIMS/INTRODUCTION: Although high-dose glucocorticoids have been reported to cause
      new-onset diabetes mellitus (glucocorticoid-induced diabetes mellitus), its risk
      factors have remained to be determined. We investigated the risk factors related
      to glucocorticoid-induced diabetes mellitus diagnosed within 2 months after the
      high-dose treatment (newly treated with an initial high dose of > 20 mg
      prednisolone (PSL) equivalent per day for at least more than 6 months) in
      collagen vascular diseases. METHODS: A total of 2,631 patients with collagen
      vascular diseases was registered between 1986 and 2006 in the Chiba-Shimoshizu
      Rheumatic Cohort. We analyzed 681 patients newly treated with high-dose
      glucocorticoid who did not have diabetes mellitus and/or its previous diagnosis
      (age: 46.3 +/- 16.7 years, PSL dose: 40.0 +/- 14.1 mg/day). Glucocorticoid
      induced diabetes mellitus was diagnosed by two or more glucose measurements in
      patients with fasting glycaemia >= 7 mmol/L and 120 minutes post-load glycaemia
      >= 11.1 mmol/L. RESULTS: Glucocorticoid-induced diabetes mellitus was observed in
      26.3% of patients, and the glucocorticoid-induced diabetes mellitus group had
      higher age, higher BMI, lower rates of females and systemic lupus erythematosus,
      higher rates of smoking, alcohol use, and microscopic polyangiitis. Multivariate
      logistic regression analysis demonstrated that the risk of glucocorticoid-induced
      diabetes mellitus was independently higher in every 10-year increment of initial
      age with adjusted odds ratio (OR) 1.556 (95% confidence interval: 1.359 - 1.783),
      in every 1 kg/m2 increment of BMI with OR 1.062 (1.002 - 1.124), in current
      smoking with OR 1.664 (1.057 - 2.622), and in every 10 mg increment of initial
      dose of prednisolone with OR 1.250 (1.074 - 1.454). CONCLUSIONS: High-dose
      glucocorticoids caused diabetes mellitus with high prevalence within a short
      period, and current smokers should be considered at higher risk of
      glucocorticoidinduced diabetes mellitus in addition to age, BMI, and initial
      dose.

PMID- 25997547
TI  - CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelic
      dependent manner.
AB  - OBJECTIVE: CYP3A4*1G (G > A) in human CYP3A4 intron 10 is associated with
      therapeutic effects of CYP3A4-metabolized drugs. The aim of this study was to
      predict its function in the regulation of CYP3A4 expression. METHODS: Functional
      analysis of the CYP3A4*1G allele was performed using bioinformatic methods and
      enhancer or promoter reporter assays in HepG2 cells. RESULTS: Transcription
      regulatory elements like CAATboxes, TATA-boxes, Sp1, SMARCA3.01, and Box II-like
      sequence were present in the intron 10 of CYP3A4. SMARCA3.01 and Box II-like
      sequence were responsible for differential binding of transcription factors on
      the CYP3A4*1G allele. In CYP3A4*1G, the G allele enhanced expression of the
      CYP3A4 promoter in a position-dependent and orientation-dependent manner,
      however, the A allele enhanced expression of the CYP3A4 promoter in a position
      independent and orientation-independent manner. In addition, the G allele and the
      A allele both displayed strong transcriptional activation, but the latter showed
      higher promoter activity than the former. Also, the A allele showed greater
      activity than the CYP3A4 promoter. CONCLUSION: These results in vitro suggest
      that CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an
      allelic-dependent manner.

PMID- 25997549
TI  - Earlier identification of risks: cumulative probability analysis of time to
      safety alerts for therapeutic monoclonal antibodies.
AB  - OBJECTIVE: Previous analysis of US FDA Medwatch safety alerts for monoclonal
      antibody therapeutics demonstrated that premarketing clinical trials can predict
      more than half of safety concerns. We expanded this analysis to assess whether
      the predictable alerts are detected sooner than the unpredictable alerts.
      METHODS: Times to alert were compared using Mann-Whitney test, Kolmogorov-Smirnov
      test, and using curves displaying cumulative frequencies of alerts over time.
      RESULTS: Until December 31, 2013 inclusive, 76 Medwatch alerts for therapeutic
      monoclonal antibodies were reported: 43 predictable vs. 33 unpredictable.
      Predictable alerts were reported at a median (IQR) of 41 (19-77) months after
      approval vs. 53 (23-73) months for the unpredictable alerts. The mean (SE) was
      52.07 (6.69) months and 55.91 (7.06) months for the predictable and
      unpredictable, respectively. Although the difference of 12 months between medians
      of time to alert was observed, the difference was not demonstrated as
      significant. Cumulative frequency curves show that predictable alerts were
      detected sooner until month 73 after approval, when ~ 80% of alerts were
      detected. Immunological reactions (such as infusion reactions, anaphylaxis, and
      reactions due to antibodies) were identified early; all 12 such alerts were
      released before the curves of cumulative frequencies cross at month 73. On the
      other hand, reactions occurring after the curves cross are predominantly late
      occurring cancers and opportunistic infections. CONCLUSIONS: The results imply
      that focus on predictable reactions defined as potential risks may play a role in
      early detection of important safety concerns.

PMID- 25997548
TI  - Effects of renal insufficiency on the elimination of fluorescein lisicol
      (NRL972), an investigational marker of hepatic transporter function.
AB  - BACKGROUND: NRL972 (Fluorescein Lisicol), a fluorescent-labelled bile salt, is an
      investigational marker of hepatic biliary transporter function. OBJECTIVE: To
      investigate the pharmacokinetics (PK) of NRL972 in patients with severe (SRI:
      creatinine clearance (CLCr)<30 mL/min per 1.73 m2 body surface area (BSA)) and
      mild-to-moderate renal insufficiency (MRI: 30<=CLCr<80 mL/min) relative to
      matched controls (CON: CLCr>=90 mL/min). METHODS: The plasma and urinary PK of
      NRL972 were determined after single 2-mg doses of NRL972 administered by 15
      second intravenous (IV) injection. The PK were derived noncompartmentally using
      all data points up to 6 hours after dosing or only using the concentrations at 10
      and 30 minutes after injection. RESULTS: 17, 22, and 16 subjects were enrolled in
      the SRI, MRI, and CON group, respectively. NRL972 was hardly quantifiable in
      urine in any of the subjects groups. The plasma concentrations of NRL972 declined
      rapidly after dosing in mostly monoexponential fashion. The decline tended to be
      faster in patients with renal insufficiency: in SRI patients, the point and 95%
      confidence interval (CI) estimates of the group ratios (SRI/CON) were 0.691 (CI:
      0.517 to 0.925) for the C(30):C(10) concentration ratio, 0.785 (CI: 0.634 to
      0.970) for t1/2, and 1.344 (CI: 1.028 to 1.757) for bodyweight normalized
      clearance (CL/BW); in MRI patients, the effect was slightly less. CONCLUSION:
      Renal insufficiency does not impair the elimination of NRL972; instead, there is
      a trend of enhanced NRL972 disposition in patients with compromised renal
      function. Concomitant renal impairment is unlikely to have confounding effects on
      the evaluation of hepatic function by NRL972 testing.

PMID- 25997550
TI  - Formulation and bioequivalence of two sildenafil 50 mg film-coated tablets after
      a single oral administration.
AB  - OBJECTIVE: The aims of this study were to establish a bioanalytical method and to
      evaluate the bioequivalence of two drug products; a generic sildenafil 50 mg film
      coated vs. the brand drug Viagra(r) 50 mg film-coated tablets. METHOD:
      Bioequivalence of tablets was tested by comparisons against the reference brand
      product in accordance with the requirements of the Declaration of Helsinki, the
      current Good Clinical Practice (GCP) Guidelines and the International Conference
      Harmonization (ICH). RESULTS: The relationship between concentration and peak
      area ratio was found to be linear within the range of 1.435 - 410.023 ng/mL for
      sildenafil. The correlation coefficient (r) was always greater than 0.99 during
      the course of the validation Statistical comparison of the main pharmacokinetic
      parameters showed no significant difference between test and reference. The 90%
      CIs of geometric mean ratios (test to reference ratios) were 99.656%, 99.806%,
      and 109.227% for AUC(0-last), AUC(0-infinity), and C(max), respectively. These
      pharmacokinetic parameter values lie within the FDA and European Medicines Agency
      specified bioequivalence limit (80 - 125%). Both formulations were well tolerated
      by all subjects and they were discharged in good health. CONCLUSION: The tested
      drug product was bioequivalent to the reference drug and had the same safety
      profile.

PMID- 25997551
TI  - Successful use of infliximab and tacrolimus in a patient with Crohn's disease.
AB  - OBJECTIVE: To report a case of successful use of infliximab (IFX) and tacrolimus
      (TAC) in a patient with Crohn's disease (CD). CASE SUMMARY: A 42-year-old man
      with no significant previous medical history was referred to our emergency
      department because of a 3-month history of weight loss, severe abdominal pain,
      and bloody diarrhea. His Harvey Bradshaw Index was 39. Ileocolonoscopic revealed
      severe Crohn colitis. Treatment with IFX 5 mg/kg, azathioprine 2.5 mg/kg/day and
      corticosteroids was started. After a second IFX infusion, he remained with
      symptoms with a Harvey Bradshaw Index of 17. An IFX dose intensification of 10
      mg/kg every 8 weeks was prescribed. After 16 weeks, a new colonoscopic
      examination revealed multiple deep ulcerations in sigma and rectum. IFX was
      intensified to 10 mg/kg every 6 weeks. After 4 doses of IFX intensified dose, the
      patient's clinical condition was not improved, with a Harvey Bradshaw Index of
      10. Azathioprine (AZA) 2.5 mg/kg/day was suspended. Tacrolimus 0.2 mg/kg/day as a
      compassionate use was added to IFX 10 mg/kg every 6 weeks. After 6 months of
      combination therapy, the patient was in clinical remission. His Harvey Bradshaw
      Index was 3. After 1 year on combination IFX and TAC therapy, the patient
      continued in clinical remission. CONCLUSIONS: This case documents that the
      combination therapy of IFX and TAC could be selected as an effective approach for
      patients with CD refractory to IFX dose-intensification plus AZA. However,
      further studies need to be performed to evaluate the efficacy of this combination
      therapy.

PMID- 25997552
TI  - Free breathing contrast-enhanced time-resolved magnetic resonance angiography in
      pediatric and adult congenital heart disease.
AB  - BACKGROUND: Contrast enhanced magnetic resonance angiography (MRA) is generally
      performed during a long breath-hold (BH), limiting its utility in infants and
      small children. This study proposes a free-breathing (FB) time resolved MRA (TRA)
      technique for use in pediatric and adult congenital heart disease (CHD). METHODS:
      A TRA sequence was developed by combining spiral trajectories with sensitivity
      encoding (SENSE, x4 kx-ky and x2 kz) and partial Fourier (75% in kz). As no
      temporal data sharing is used, an independent 3D data set was acquired every
      ~1.3s, with acceptable spatial resolution (~2.3x2.3x2.3 mm). The technique was
      tested during FB over 50 consecutive volumes. Conventional BH-MRA and FB-TRA data
      was acquired in 45 adults and children with CHD. We calculated quantitative image
      quality for both sequences. Diagnostic accuracy was assessed in all patients from
      both sequences. Additionally, vessel measurements were made at the sinotubular
      junction (N = 43), proximal descending aorta (N = 43), descending aorta at the
      level of the diaphragm (N = 43), main pulmonary artery (N = 35), left pulmonary
      artery (N = 35) and the right pulmonary artery (N = 35). Intra and inter observer
      variability was assessed in a subset of 10 patients. RESULTS: BH-MRA had
      significantly higher homogeneity in non-contrast enhancing tissue (coefficient of
      variance, P <0.0001), signal-to-noise ratio (P <0.0001), contrast-to-noise ratio
      (P <0.0001) and relative contrast (P = 0.02) compared to the FB-TRA images.
      However, homogeneity in the vessels was similar in both techniques (P = 0.52) and
      edge sharpness was significantly (P <0.0001) higher in FB-TRA compared to BH-MRA.
      BH-MRA provided overall diagnostic accuracy of 82%, and FB-TRA of 87%, with no
      statistical difference between the two sequences (P = 0.77). Vessel diameter
      measurements showed excellent agreement between the two techniques (r = 0.98, P
      <0.05), with no bias (0.0 mm, P = 0.71), and clinically acceptable limits of
      agreement (-2.7 to +2.8 mm). Inter and intra observer reproducibility showed good
      agreement of vessel diameters (r>0.988, P<0.0001), with negligible biases
      (between -0.2 and +0.1mm) and small limits of agreement (between -2.4 and
      +2.5mm). CONCLUSIONS: We have described a FB-TRA technique that is shown to
      enable accurate diagnosis and vessel measures compared to conventional BH-MRA.
      This simplifies the MRA technique and will enable angiography to be performed in
      children and adults whom find breath-holding difficult.

PMID- 25997553
TI  - School-based health interventions should be assessed with measures of fitness and
      fatness: comment on 'Beyond the randomised controlled trial and BMI--evaluation
      of effectiveness of through-school nutrition and physical activity programmes'.

PMID- 25997554
TI  - Delayed endoscopic retrograde cholangiopancreatography is associated with
      persistent organ failure in hospitalised patients with acute cholangitis.
AB  - BACKGROUND: Predictors of organ failure and the impact of early endoscopic
      retrograde cholangiopancreatography (ERCP) on outcomes in patients with acute
      cholangitis are unclear. AIM: To identify factors associated with persistent
      organ failure and assess the impact of early ERCP on outcomes in hospitalised
      patients with cholangitis. METHODS: Consecutive hospitalised patients who
      received ERCP at two centres for cholangitis from 4/2005-3/2013 were
      retrospectively reviewed. Delayed ERCP was defined as ERCP >= 48 h after
      hospitalisation. Primary outcome was persistent organ failure at >48 h after
      hospitalisation (>= 1.5 times rise in creatinine levels from baseline values to
      >= 1.5 mg/dL or need for dialysis, mechanical ventilation and/or hypotension
      requiring vasopressor). RESULTS: 203 patients (mean age 59 +/- 19 years) had ERCP
      for cholangitis: 115 with choledocholithiasis, 48 with other benign obstructions
      and 40 with malignant strictures. Forty-five (22%) patients had persistent organ
      failure at >48 h and 11 (5%) died. On multivariate analysis, Charlson Comorbidity
      Index >2 (OR = 4.6, 95% CI = 1.5-13.8), systemic inflammatory response syndrome
      (SIRS; OR = 3.2, 95% CI = 1.1-9.8), hypoalbuminemia (OR = 3.3, 95% CI = 1.4-7.9),
      bacteremia (OR = 2.8, 95% CI 1.3-6.2) and delayed ERCP(OR = 3.1, 95% CI: 1.4-7.0)
      were associated with persistent organ failure. Every 1-day delay in ERCP was
      associated with a 17% (95% CI = 5-29%) relative risk increase in persistent organ
      failure after adjusting for significant factors. CONCLUSIONS: Delay in ERCP
      beyond 48 h was associated with persistent organ failure in hospitalised patients
      with acute cholangitis. Other factors included increased comorbidities, SIRS,
      hypoalbuminemia and bacteremia. Early ERCP performed within 48 h after
      presentation in patients with cholangitis may improve outcomes.

PMID- 25997555
TI  - Zerumbone, A Natural Cyclic Sesquiterpene, Promotes ABCA1-Dependent Cholesterol
      Efflux from Human THP-1 Macrophages.
AB  - This study was conducted to explore the effect of zerumbone, isolated from
      Zingiberzerumbet Smith, on apolipoprotein A-I (apoA-I)-mediated cholesterol
      efflux from THP-1 macrophages. THP-1 macrophages were treated with different
      concentrations (10-100 MUmol/l) of zerumbone and cholesterol efflux was measured.
      The involvement of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 and
      ERK1/2 signaling was checked. Notably, zerumbone caused a concentration-dependent
      induction of ABCA1 but not ABCG1, coupled with enhanced phosphorylation of
      ERK1/2. Pre-treatment with PD98059 (a potent ERK1/2 inhibitor) significantly
      blocked the upregulation of ABCA1 by zerumbone. Small interfering RNA-mediated
      downregulation of ABCA1 but not ABCG1 significantly impaired the promotion of
      apoA-I-mediated cholesterol efflux by zerumbone. Taken together, zerumbone has
      the capacity to facilitate apoA-I-mediated cholesterol efflux from macrophages
      through the activation of ERK1/2 signaling and upregulation of ABCA1.

PMID- 25997556
TI  - Chitosan Influences the Expression of P-gp and Metabolism of Norfloxacin in Grass
      Carp.
AB  - The aim of this study was to investigate the relationship between the
      administration of chitosan (CTS), expression of permeability glycoprotein (P-gp),
      and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella.
      Fish were administrated with a single dose of either NOR, CTS, 1:5 NOR-CTS or
      1:10 NOR-CTS. The P-gp expression was analyzed by immunohistochemistry and real
      time-PCR. The concentration of NOR was determined using HPLC. The mRNA and
      protein expression of P-gp in the fish intestine was significantly enhanced
      following a single dosage of 40 mg/kg NOR, and peak expression occurred at 3 h
      after drug administration (P < 0.05). A single dosage of both 1:5 NOR-CTS and
      1:10 NOR-CTS reduced the intestinal P-gp expression to levels significantly lower
      than that from NOR alone (P < 0.05), but significantly higher than that from the
      control (P < 0.05). Interestingly, CTS alone also led to a slight decrease in P
      gp expression. In addition, pharmacokinetic assays revealed a marked increase in
      area under the curve (AUC) of NOR with 1:5 and 1:10 NOR-CTS, by approximately 1.5
      fold and threefold, respectively. Finally, the relative bioavailability of NOR
      after a single oral dosage of 1:5 and 1:10 NOR-CTS was enhanced to 148.02% and
      304.98%, respectively. In this study, we demonstrated that the transmembrane
      glycoprotein P-gp regulates NOR metabolism in the intestine of Grass Carp,
      suggesting that NOR may be a direct substrate of P-gp. More importantly, we
      showed that CTS can inhibit P-gp expression in a dose-dependent manner and
      improve the relative bioavailability of NOR in this species.

PMID- 25997557
TI  - Correlation between nipple elevation and breast resection weight: How to
      preoperatively plan breast reduction.
AB  - Breast hypertrophy is often associated with functional limitations. Beyond the
      aesthetic concerns, breast reduction can improve symptoms and self-esteem. In
      different countries, health-care system regulations have fixed the threshold for
      reimbursement in 500 g of predicted tissue resection for each breast. Different
      preoperative measurements have been proposed to predict breast-tissue weight to
      be removed, showing a variable correlation with post-operative evaluation. We
      describe a reliable, simple measurement to predict the quantity of breast
      reduction in grams, which can be applicable to any surgical technique. A total of
      128 patients undergoing bilateral breast reduction were evaluated. The
      correlation between the preoperative nipple-areola complex (NAC) lift distance
      and the weight of removed breast tissue was tested with linear regression and
      Pearson's test. Other anthropometric measurements were tested as a control. The
      ratio between resected grams and lift distance was explored to find a
      multiplication coefficient to be used at preoperative planning. The mean
      resection weight was 686.65 g. The mean NAC-lift distance was 7.6 cm. Positive
      correlation between the NAC-lift distance and the weight of breast tissue removed
      was found (r: 0.87; p < 0.001). The mean weight of the removed breast tissue (g)
      per centimetre of NAC lift was 81 g/cm in the group between 6 and 12 cm and 70
      g/cm in the group with >12 cm of lift distance. The NAC-lift distance is a
      single, objective, repeatable measure that can provide a reliable prediction of
      breast-tissue grams to be removed; it helps in classifying breast-reduction
      indications.

PMID- 25997558
TI  - Prospective evaluation of ambulatory laser vaporization of the prostate for
      benign prostatic hyperplasia.
AB  - BACKGROUND AND OBJECTIVE: Photoselective vaporization of the prostate (PVP) is an
      alternative to transurethral resection of the prostate in the surgical treatment
      of benign prostatic hyperplasia (BPH). Our objective was to prospectively
      evaluate the feasibility, safety, and efficacy of ambulatory photoselective
      vaporization of the prostate for benign prostatic hyperplasia. MATERIALS AND
      METHODS: We prospectively collected data of all consecutive patients who
      underwent ambulatory PVP with the Greenlight((r)) laser 180-W XPS at two centers
      between May 2012 and June 2013. Patients' characteristics, perioperative data,
      postoperative outcomes, complications, and patient's satisfaction were evaluated.
      Successful ambulatory care procedure was defined as the ability to leave the
      hospital in the evening of the operation. RESULTS: The ambulatory procedure was
      intended in 134 patients. Mean age was 67 years. Mean prostate volume was 54 ml,
      and Median American Society Anesthesiologists (ASA) score was 2. Ambulatory
      procedure was successful in 121 patients (90%). At 3 months, International
      Prostate Symptom Score (7.3 +/- 4.9), maximal urinary flow rate (20.8 +/- 7.6
      ml/s), postvoid residual urine (19.2 +/- 71 ml), and quality of life (1.6 +/-
      1.4) were significantly improved (P < 0.001). Fourteen patients (10.5%) had
      complications that were all minor (Clavien <= 2). Two patients had to be
      readmitted to the hospital. The majority of patients (89%) were satisfied with
      ambulatory care. Failure to complete ambulatory procedure was mostly related to
      logistical problem (70% of the cases). CONCLUSIONS: Ambulatory PVP is feasible
      with functional results and complications comparable to that of traditional
      hospitalization. Ambulatory care yields high patient's satisfaction.

PMID- 25997559
TI  - Locked minimally invasive plating versus fourth generation nailing in the
      treatment of AO/OTA 31A2.2 fractures: A biomechanical comparison of PCCP((r)) and
      Intertan nail((r)).
AB  - INTRODUCTION: Locked minimally invasive plating and fourth generation nailing
      potentially could reduce the complication rate in the treatment of trochanteric
      femur fractures by its rotational stability and providing better lateral cortical
      support. The purpose of this study was (1) to compare the biomechanical
      properties of the Percutaneous compression plate (PCCP) and the Intertan nail
      (IT) with regards to implant failure and (2) to assess dynamic stability
      coefficients in an unstable AO/OTA 31A2.2 fracture model. METHODS: In paired
      femurs, a standardised unstable trochanteric femur fracture was induced by an
      oscillating saw. The fractures were stabilised by either the PCCP (Orthofix,
      McKinney, TX, USA) or the IT (Smith & Nephew, Memphis, TN, USA). All femurs were
      loaded with 300N, followed by an increase in load until failure using 300N each
      time (2000 cycles each, 0.5Hz). After every load step the samples were assessed
      visually and radiographically. We measured migration and performed a survival
      analysis. RESULTS: 16 fractures were induced in 8 paired human specimens (mean
      age: 84 years, 61-100 years). The mean stiffness (PCCP vs. IT: 249+/-124N/mm vs.
      273+/-153N/mm; p=0.737) was comparable. The IT proved superior to the PCCP with
      regard to the number of cycles reached before failure occurred (PCCP vs. IT:
      12,691+/-4733 vs. 15,313+/-4875 cycles; p=0.023). Except for a higher axial
      migration of the IT at failure point (PCCP vs. IT: 1.3mm vs. 4.3mm; p=0.028)
      there were no differences between the intra- and extramedullary implants, not
      even in terms of rotational stability along the femoral neck axis. A fracture of
      the femoral neck caused test abortion in both implants in most cases. CONCLUSION:
      This study showed a superiority of the IT compared with the PCCP with regards to
      number of cycles achieved under sequential load increases for unstable
      trochanteric femur fractures. The stiffness was comparable. Both implants showed
      a high rotational stability and a support of the lateral wall. STUDY TYPE:
      Biomechanical study.

PMID- 25997560
TI  - Pre-operative nutritional serum parameters as predictors of failure after
      internal fixation in undisplaced intracapsular proximal femur fractures.
AB  - INTRODUCTION: Current management of undisplaced hip fractures is based on
      internal fixation. Reported revision rates of 12-17% for this procedure
      negatively impact on patient morbidity and mortality. The aim of this novel study
      is to examine if the nutritional status of these patients is associated with
      failure of internal fixation. PATIENTS AND METHODS: A consecutive series of 111
      undisplaced intracapsular hip fractures treated with cannulated screw was
      identified. These were retrospectively reviewed including routine admission serum
      investigations (lymphocyte count and albumin levels). Radiological investigations
      were used to assess fracture classification, posterior-tilt angle, fixation
      adequacy, screw configuration and failure (avascular-necrosis, non-union and
      screw cut-out). RESULTS: 16% of fixations failed (18 patients). Patients with
      fixation-failure had a significantly lower albumin (35g/l vs. 40g/l, p=0.02) and
      lymphocyte count (0.7*10(9)l vs. 1.4*10(9)l, p<=0.001) than non-failure patients.
      Lymphocyte count, albumin level and posterior-tilt angle were independent
      predicators of failure on binary logistic regression analysis. We suggest that
      routine laboratory tests can be used to identify patients at greatest risk of
      failure of internal fixation.

PMID- 25997561
TI  - Differences in calpain system, desmin degradation and water holding capacity
      between commercial Meishan and Duroc * Landrace * Yorkshire crossbred pork.
AB  - The objective of this study was to examine the differences in calpain system,
      desmin degradation, pH values and water holding capacity (WHC) between muscles of
      commercial Meishan and Duroc * Landrace * Yorkshire crossbred pigs. Meishan pork
      presented better WHC evidenced by lower purge loss at days 1 and 3 and less
      centrifugation loss at day 1 post mortem (P < 0.05). pH values at 45 min post
      mortem in Meishan pork were significantly higher compared to crossbred pork (P <
      0.05). Calpain-1 messenger RNA (mRNA) expression was lower in Meishan pork
      compared to that from crossbred pork (P < 0.05). Additionally, calpain-1
      activity, the ratio of calpain-1 to calpastatin activity and desmin degradation
      were lower in Meishan pork compared to those from crossbred pork samples (P <
      0.05). The results indicate that the calpain system including mRNA expression and
      activity were different between commercial Meishan and crossbred pork resulting
      in difference in the degree of desmin degradation during post mortem aging. pH
      values at 45 min and 24 h post mortem rather than calpain activity and desmin
      degradation could explain the higher water holding capacity in commercial Meishan
      pork. 

PMID- 25997562
TI  - A Clinical Profile of 125 Patients with Writer's Cramp.
AB  - BACKGROUND: The characteristics of writer's cramp (WC) may vary according to
      native languages and scripts. We report the clinical profile of a large cohort of
      patients with WC from India. METHODS: A chart review of 125 patients (F:M =
      16:109) with WC seen over 10 years at the National Institute of Mental Health and
      Neurosciences (NIMHANS), India. RESULTS: The mean age of patients was 36.8 +/-
      14.3, the mean age at onset (AAO) of symptoms was 31.5 +/- 2.7 and the mean
      duration of difficulty in writing was 5.3 +/- 6.3. The most common presenting
      complaint while writing was pain in the forearm (56%), followed by tremulousness
      of hand (28.8%) and abnormal posturing of hand (15.2%). Along with writing
      difficulty, 5.6% had difficulty in typing. The mean AAO of writing difficulty was
      significantly earlier in women than in men (22.8 +/- 3.5 vs. 32.8 +/- 4.2 years,
      p < 0.001). While writing, excessive extension (41.6%) of wrist was the most
      common abnormality, followed by excessive flexion (37.6%) and extension (19.2%)
      of index finger. CONCLUSIONS: Women with WC have a significantly earlier age of
      onset than men. Excessive extension of wrist with flexion of thumb and index
      finger were the most common abnormalities noted in WC.

PMID- 25997563
TI  - Nesfatin-1 Suppresses Cardiac L-type Ca2+ Channels Through Melanocortin Type 4
      Receptor and the Novel Protein Kinase C Theta Isoform Pathway.
AB  - BACKGROUND/AIMS: Nesfatin-1 (NF-1), an anorexic nucleobindin-2 (NUCB2)-derived
      hypothalamic peptide, acts as a peripheral cardiac modulator and it can induce
      negative inotropic effects. However, the mechanisms underlying these effects in
      cardiomyocytes remain unclear. METHODS: Using patch clamp, protein kinase assays,
      and western blot analysis, we studied the effect of NF-1 on L-type Ca2+ currents
      (ICa,L) and to explore the regulatory mechanisms of this effect in adult
      ventricular myocytes. RESULTS: NF-1 reversibly decreased ICa,L in a dose
      dependent manner. This effect was mediated by melanocortin 4 receptor (MC4-R) and
      was associated with a hyperpolarizing shift in the voltage-dependence of
      inactivation. Dialysis of cells with GDP-beta-S or anti-Gbeta antibody as well as
      pertussis toxin pretreatment abolished the inhibitory effects of NF-1 on ICa,L.
      Protein kinase C (PKC) antagonists abolished NF-1-induced responses, whereas
      inhibition of PKA activity or intracellular application of the fast Ca2+-chelator
      BAPTA elicited no such effects. Application of NF-1 increased membrane abundance
      of PKC theta isoform (PKCtheta), and PKCtheta inhibition abolished the decrease
      in ICa,L induced by NF-1. CONCLUSION: These data suggest that NF-1 suppresses L
      type Ca2+ channels via the MC4-R that couples sequentially to the betagamma
      subunits of Gi/o-protein and the novel PKCtheta isoform in adult ventricular
      myocytes.

PMID- 25997565
TI  - Imido-pyridine Ti(IV) compounds: synthesis of unusual imido-amido
      heterobimetallic derivatives.
AB  - The reaction of lithiated picolines and [TiCl3(eta(5)-C5Me5)] leads to several
      bridging or terminal imido compounds, each of which can be selectively formed by
      controlling the stoichiometry and temperature. Specifically, the dinuclear imido
      bridged [TiCl(eta(5)-C5Me5)(MU-NR)]2 (1a, NR = 2-imido-3-picoline; 1b, NR = 2
      imido-5-picoline) species and the unusual Ti-Li imido-amido heterobimetallic
      complex [{Li(THF)}{Ti(eta(5)-C5Me5)(NR)(NHR)2}] (2a, NR = 2-imido-3-picoline; 2b,
      NR = 2-imido-5-picoline) were isolated. Compounds 2 are in effect the first
      structurally characterized examples of titanium(IV) coordinated to terminal imido
      pyridines. DFT-D calculations for 2a denote a multiple bond character between
      titanium and the imido ligand and a strong polarization of the electron density
      by the alkali cation in spite of the lack of intermetallic bonding.

PMID- 25997564
TI  - Respiratory disease in pregnancy.
AB  - Many physiological and anatomical changes of pregnancy affect the respiratory
      system. These changes often affect the presentation and management of the various
      respiratory illnesses in pregnancy. This article focuses on several important
      respiratory issues in pregnancy. The management of asthma, one of the most common
      chronic illnesses in pregnancy, remains largely unchanged compared to the
      nonpregnant state. Infectious respiratory illness, including pneumonia and
      tuberculosis, are similarly managed in pregnancy with antibiotics, although
      special attention may be needed for antibiotic choices with more pregnancy safety
      data. When mechanical ventilation is necessary, consideration should be given to
      the maternal hemodynamics of pregnancy and fetal oxygenation. Maintaining
      maternal oxygen saturation above 95% is recommended to sustain optimal fetal
      oxygenation. Cigarette smoking has known risks in pregnancy, and current practice
      guidelines recommend offering cognitive and pharmacologic interventions to
      pregnant women to assist in smoking cessation. 

PMID- 25997566
TI  - Regulatory landscape for cell therapy--EU view.
AB  - This article addresses regulation of cell therapies in the European Union (EU),
      covering cell sourcing and applications for clinical trials and marketing
      authorisation applications. Regulatory oversight of cell sourcing and review of
      applications for clinical trials with cell therapies are handled at national
      level, that is, separately with each country making its own decisions. For
      clinical trials, this can lead to different decisions in different countries for
      the same trial. A regulation is soon to come into force that will address this
      and introduce a more efficient clinical trial application process. However, at
      the marketing authorisation stage, the process is pan-national: the Committee for
      Human Medicinal Products (CHMP) is responsible for giving the final scientific
      opinion on all EU marketing authorisation applications for cell therapies:
      favourable scientific opinions are passed to the European Commission (EC) for
      further consultation and, if successful, grant of a marketing authorisation valid
      in all 28 EU countries. In its review of applications for marketing
      authorisations (MAAs) for cell therapies, the CHMP is obliged to consult the
      Committee for Advanced Therapies (CAT), who conduct detailed scientific
      assessments of these applications, with assessment by staff from national
      regulatory authorities and specialist advisors to the regulators. 

PMID- 25997567
TI  - Evaluation of infectivity and reverse transcriptase real-time polymerase chain
      reaction assays for detection of xenotropic murine leukemia virus used in virus
      clearance validation.
AB  - Infectivity and reverse transcriptase quantitative real-time polymerase chain
      reaction (qRT-PCR) assays have been optimized and validated for xenotropic murine
      leukemia virus (X-MuLV) detection. We have evaluated the assays systematically
      with regard to specificity, linearity, lower limit of detection (LLOD), lower
      limit of quantification (LLOQ), and precision. Both assays are specific for X
      MuLV detection, with a linear detection range of 0.6-5.6 log(10) TCID(50)/mL for
      the infectivity assay, and 1.4-6.5 log(10) particles/mL for the qRT-PCR assay.
      The LLOD and LLOQ of the infectivity and the qRT-PCR assays are determined as 0.5
      and 1.0 log(10)/mL, and 1.4 and 2.2 log(10)/mL. The inter-assay repeatability of
      qRT-PCR assay (4.2% coefficient of variation [CV]) is higher than the infectivity
      assay (7.9% CV). We have shown that both assays are closely correlated (r = 0.85,
      P < 0.05, n = 22). The particle/infectivity ratio is determined as 66. Both
      assays were applied to evaluate virus removal using virus clearance samples of
      chromatographic and filtration processes. Here, we have demonstrated that the qRT
      PCR assay is much faster in testing and is approximately 8-fold more sensitive
      than the infectivity assay. Therefore, the qRT-PCR assay can replace the
      infectivity assay in many cases, but both assays are complementary in elucidating
      the mechanism of virus inactivation and removal in virus clearance validation.

PMID- 25997568
TI  - Principles of Organization of the Dorsal Lateral Geniculate Nucleus.

PMID- 25997569
TI  - Being two is better than one-catalytic reductions with dendrimer encapsulated
      copper- and copper-cobalt-subnanoparticles.
AB  - Copper and copper-cobalt subnanoparticles have been synthesized using 4
      carbomethoxypyrrolidone terminated PAMAM-dendrimers as templates. The metal
      particles were applied in catalytic reduction reactions. While Cu
      subnanoparticles were only capable of reducing conjugated double bonds, enhancing
      the Cu particles with Co led to a surprising increase in catalytic activity,
      reducing also isolated carbon double and triple bonds. 

PMID- 25997570
TI  - Retention time of chlorophacinone in black-tailed prairie dogs informs secondary
      hazards from a prairie dog rodenticide bait.
AB  - BACKGROUND: Secondary toxicity in mammals and birds that consume animals
      containing residues of anticoagulant rodenticides represents a persistent
      conflict between conservation, agriculture and environmental contamination.
      Chlorophacinone residues in black-tailed prairie dogs (Cynomys ludovicianus)
      represent a secondary exposure hazard to predatory and scavenging avian and
      mammalian species in the Central Plains of the United States, especially
      considering efforts to re-establish black-footed ferrets (Mustela nigripes).
      Rozol((r)) Prairie Dog Bait (chlorophacinone 0.005%) is registered to control
      black-tailed prairie dogs in ten states throughout the midwestern and western
      United States. RESULTS: We fed Rozol Prairie Dog Bait to captive black-tailed
      prairie dogs for 2 days and analyzed their livers and whole bodies (without
      livers) for chlorophacinone residue on days 3, 5, 7, 9, 11, 14, 18 and 27 post
      exposure. We found the greatest levels of residues in livers (x? = 5.499 mg kg(
      1) ) and whole bodies (x? = 1.281 mg kg(-1) ) on day 3. Residues in both tissues
      declined rapidly over time, with estimated half-lives of approximately 6 days
      post-exposure. However, a risk assessment of secondary toxicity to non-target
      mammals indicated acute risks for mammalian species up to 27 days post-exposure
      and negligible risks for birds. CONCLUSION: The results suggest that the greatest
      risk of secondary toxicity occurs <=14 days post-application of Rozol Prairie Dog
      Bait and declines thereafter. This corresponds to the time when chlorophacinone
      residues are high, and prairie dogs exhibit signs of intoxication and are perhaps
      most susceptible to predation and scavenging. These results confirm that Rozol
      Prairie Dog Bait should not be used in areas where black-footed ferrets or other
      sensitive species occur. Published 2015. This article is a U.S. Government work
      and is in the public domain in the USA.

PMID- 25997571
TI  - Smart Albumin-Biomineralized Nanocomposites for Multimodal Imaging and
      Photothermal Tumor Ablation.
AB  - Smart cyanine-grafted gadolinium oxide nanocrystals (Cy-GdNCs) obtained by
      albumin-based biomineralization are shown to be theranostic nanocomposites, with
      promising properties for trimodal near-infrared
      fluorescence/photoacoustics/magnetic-resonance imaging-guided photothermal tumor
      ablation. 

PMID- 25997572
TI  - Pegylated interferon (alone or with ribavirin) for chronic hepatitis C in
      haemodialysis population.
AB  - BACKGROUND/AIMS: Hepatitis C virus infection remains prevalent among patients
      undergoing long-term haemodialysis and has a detrimental impact on survival in
      this population. Antiviral therapy for chronic hepatitis C in haemodialysis
      patients is still a challenge to clinicians. The aim of the current study is to
      evaluate the efficacy and safety of therapy with pegylated interferon, alone or
      combined with ribavirin, for chronic hepatitis C among patients undergoing long
      term hemodialysis. METHODS: We conducted a retrospective, multicenter cohort
      trial with monotherapy (pegylated interferon) (n=21) or combined antiviral
      therapy (pegylated interferon plus ribavirin) (n=5) for chronic hepatitis C in
      patients undergoing long-term haemodialysis. RESULTS: Sustained virological
      response was obtained in eleven (42%) patients. Seven (26.9%) patients
      interrupted prematurely the antiviral treatment due to serious side-effects, the
      most frequent cause of treatment withdrawal being hematological (n=3). HCV RNA
      load was lower in responder than non-responder patients, 5.44 (3.45; 6.36) vs.
      5.86 (4.61; 6.46) log10 copies/mL, even if the difference was not significant
      (P=0.099). Blood transfusion requirement was greater in patients on combined
      antiviral therapy than those on pegylated interferon alone, 100% (5/5) vs. 0%
      (0/21), P=0.0001. No difference in sustained viral response occurred between
      patients on combined antiviral therapy and those on pegylated interferon
      monotherapy [40% (2/5) vs. 42.8% (9/21), P=0.90]. CONCLUSIONS: Results from this
      study showed that pegylated interferon alone or with ribavirin is unsatisfactory
      in terms of efficacy and safety. Prospective trials based on interferon-free
      regimens (i.e., sofosbuvir plus ribavirin or sofosbuvir plus daclatasvir) are
      under way in patients with hepatitis C receiving long-term hemodialysis.

PMID- 25997573
TI  - An improved I-FAST system for the diagnosis of Alzheimer's disease from
      unprocessed electroencephalograms by using robust invariant features.
AB  - OBJECTIVE: This paper proposes a new, complex algorithm for the blind
      classification of the original electroencephalogram (EEG) tracing of each
      subject, without any preliminary pre-processing. The medical need in this field
      is to reach an early differential diagnosis between subjects affected by mild
      cognitive impairment (MCI), early Alzheimer's disease (AD) and the healthy
      elderly (CTR) using only the recording and the analysis of few minutes of their
      EEG. METHODS AND MATERIAL: This study analyzed the EEGs of 272 subjects, recorded
      at Rome's Neurology Unit of the Policlinico Campus Bio-Medico. The EEG recordings
      were performed using 19 electrodes, in a 0.3-70Hz bandpass, positioned according
      to the International 10-20 System. Many powerful learning machines and algorithms
      have been proposed during the last 20 years to effectively resolve this complex
      problem, resulting in different and interesting outcomes. Among these algorithms,
      a new artificial adaptive system, named implicit function as squashing time (I
      FAST), is able to diagnose, with high accuracy, a few minutes of the subject's
      EEG track; whether it manifests an AD, MCI or CTR condition. An updating of this
      system, carried out by adding a new algorithm, named multi scale ranked
      organizing maps (MS-ROM), to the I-FAST system, is presented, in order to
      classify with greater accuracy the unprocessed EEG's of AD, MCI and control
      subjects. RESULTS: The proposed system has been measured on three independent
      pattern recognition tasks from unprocessed EEG tracks of a sample of AD subjects,
      MCI subjects and CTR: (a) AD compared with CTR; (b) AD compared with MCI; (c) CTR
      compared with MCI. While the values of accuracy of the previous system in
      distinguishing between AD and MCI were around 92%, the new proposed system
      reaches values between 94% and 98%. Similarly, the overall accuracy with best
      artificial neural networks (ANNs) is 98.25% for the distinguishing between CTR
      and MCI. CONCLUSIONS: This new version of I-FAST makes different steps forward:
      (a) avoidance of pre-processing phase and filtering procedure of EEG data, being
      the algorithm able to directly process an unprocessed EEG; (b) noise elimination,
      through the use of a training variant with input selection and testing system,
      based on naive Bayes classifier; (c) a more robust classification phase, showing
      the stability of results on nine well known learning machine algorithms; (d)
      extraction of spatial invariants of an EEG signal using, in addition to the
      unsupervised ANN, the principal component analysis and the multi scale entropy,
      together with the MS-ROM; a more accurate performance in this specific task.

PMID- 25997574
TI  - Seasonal Variation in Forebrain Region Sizes in Male Ruffed Grouse (Bonasa
      umbellus).
AB  - The song system of songbirds has provided significant insight into the underlying
      mechanisms and behavioural consequences of seasonal neuroplasticity. The extent
      to which seasonal changes in brain region volumes occur in non-songbird species
      has, however, remained largely untested. Here, we tested whether brain region
      volumes varied with season in the ruffed grouse (Bonasa umbellus), a gallinaceous
      bird that produces a unique wing-beating display known as 'drumming' as its
      primary form of courtship behaviour. Using unbiased stereology, we measured the
      sizes of the cerebellum, nucleus rotundus, telencephalon, mesopallium,
      hippocampal formation, striatopallidal complex and arcopallium across spring
      males, fall males and fall females. The majority of these brain regions did not
      vary significantly across these three groups. The two exceptions were the
      striatopallidal complex and arcopallium, both of which were significantly larger
      in spring males that are actively drumming. These seasonal changes in volume
      strongly implicate the striatopallidal complex and arcopallium as key structures
      in the production and/or modulation of the ruffed grouse drumming display and
      represent the first evidence of seasonal plasticity in the telencephalon
      underlying a non-vocal courtship behaviour. Our findings also suggest that
      seasonal plasticity in the striatopallidal complex and arcopallium might be a
      trait that is shared across many bird species and that both structures are
      related to the production of multiple forms of courtship and not just learned
      song.

PMID- 25997575
TI  - Gold nanostars coated with neutral and charged polyethylene glycols: A
      comparative study of in-vitro biocompatibility and of their interaction with SH
      SY5Y neuroblastoma cells.
AB  - Gold nanostars (GNS) have been coated with four different polyethylene glycols
      (PEGs) equipped with a -SH function for grafting on the gold surface. These PEGs
      have different chain lengths with average MW=2000, 3000, 5000 and average number
      of -O-CH2-CH2 - units 44, 66, and 111, respectively. Two are neutral and two are
      terminated with -COOH and -NH2 functions, thus bearing negative and positive
      charges at physiological pH, thanks to the formation of carboxylate and ammonium
      groups. The negative charge of the GNS coated with PEG carboxylate has also been
      exploited to further coat the GNS with the PAH (polyallylamine hydrochloride)
      cationic polymer. Vitality tests have been carried out on SH-SY5Y cells treated
      with the five differently coated GNS for 4, 24, and 48 h, at Au concentrations
      ranging from 1.25 to 100 MUg/mL. The same tests have been repeated with the pure
      PEGs and PAH. Excellent biocompatibility was found for all PEGs, independently on
      charge and chain length, both for coated GNS and for the pure polymers. On the
      contrary, poor biocompatibility was found for PAH overcoated GNS and for pure
      PAH, although the latter only at high concentrations. Exploiting the two-photon
      luminescence of GNS, we have found by confocal laser scanning microscopy that
      when GNS are coated with PEGs they do not enter SH-SY5Y cells, while when
      overcoated with PAH they massively penetrate into the cytoplasm. This causes cell
      death by dramatically changing cell morphology, as demonstrated also by atomic
      force microscopy.

PMID- 25997576
TI  - Novel mixed metal Ag(I)-Sb(III)-metallotherapeutics of the NSAIDs, aspirin and
      salicylic acid: Enhancement of their solubility and bioactivity by using the
      surfactant CTAB.
AB  - The already known Ag(I)-Sb(III) compound of the formula {Ag(Ph3Sb)3(NO3)} (1) and
      two novel mixed metal Ag(I)-Sb(III) metallotherapeutics of the formulae
      {Ag(Ph3Sb)3(SalH)}(2) and {Ag(Ph3Sb)3(Asp)}(3) (SalH2=salicylic acid,
      AspH=aspirin or 2-acetylsalicylic acid and Ph3Sb=triphenyl antimony(III)) have
      been synthesised and characterised by m.p., vibrational spectroscopy (mid-FT-IR),
      (13)C-,(1)H-NMR, UV-visible (UV-vis) spectroscopic techniques, high resolution
      mass spectroscopy (HRMS) and X-ray crystallography. Compounds 1,-3 were treated
      with the surfactant cetyltrimethylammonium bromide (CTAB) in order to enhance
      their solubility and as a consequence their bioactivity. The resulting micelles a
      c were characterised with X-ray powder diffraction (XRPD) analysis, X-ray
      fluorescence (XRF) spectroscopy, Energy-dispersive X-ray spectroscopy (EDX),
      conductivity, Thermal gravimetry-differential thermal analysis (TG-DTA), and
      atomic absorption. Compounds 1-3 and the relevant micelles a-c were evaluated for
      their in vitro cytotoxic activity against human cancer cell lines: MCF-7 (breast,
      estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative) and MRC-5
      (normal human fetal lung fibroblast cells) with sulforhodamine B (SRB)
      colorimetric assay. The results show significant increase in the activity of
      micelles compared to that of the initial compounds. Moreover, micelles exhibited
      lower activity against normal cells than tumor cells. The binding affinity of a-c
      towards the calf thymus (CT)-DNA, lipoxygenase (LOX) and glutathione (GSH) was
      studied by the fluorescent emission light and UV-vis spectroscopy. 

PMID- 25997577
TI  - Red nail folds and Gottron's sign in a patient with leukemic infiltration of
      pelvic muscles.

PMID- 25997578
TI  - Selenium-Catalyzed Oxidative C(sp(2))-H Amination of Alkenes Exemplified in the
      Expedient Synthesis of (Aza-)Indoles.
AB  - A new selenium-catalyzed protocol for the direct, intramolecular amination of
      C(sp(2))-H bonds using N-fluorobenzenesulfonimide as the terminal oxidant is
      reported. This method enables the facile formation of a broad range of diversely
      functionalized indoles and azaindoles derived from easily accessible ortho-vinyl
      anilines and vinylated aminopyridines, respectively. The procedure exploits the
      pronounced carbophilicity of selenium electrophiles for the catalytic activation
      of alkenes and leads to the formation of C(sp(2))-N bonds in high yields and with
      excellent functional group tolerance. 

PMID- 25997579
TI  - Pharyngeal arch deficiencies affect taste bud development in the circumvallate
      papilla with aberrant glossopharyngeal nerve formation.
AB  - BACKGROUND: The pharyngeal arches (PAs) generate cranial organs including the
      tongue. The taste placodes, formed in particular locations on the embryonic
      tongue surface, differentiate into taste buds harbored in distinct gustatory
      papillae. The developing tongue also has a complex supply of cranial nerves
      through each PA. However, the relationship between the PAs and taste bud
      development is not fully understood. RESULTS: Ripply3 homozygous mutant mice,
      which have impaired third/fourth PAs, display a hypoplastic circumvallate papilla
      and lack taste buds, although the taste placode is normally formed. Formation of
      the glossopharyngeal ganglia is defective and innervation toward the posterior
      tongue is completely missing in Ripply3 mutant embryos at E12.5. Moreover, the
      distribution of neuroblasts derived from the epibranchial placode is severely,
      but not completely, atenuated, and the neural crest cells are diminished in the
      third PA region of Ripply3 mutant embryos at E9.5-E10.5. In Tbx1 homozygous
      mutant embryos, which exhibit another type of deficiency in PA development, the
      hypoplastic circumvallate papilla is observed along with abnormal formation of
      the glossopharyngeal ganglia and severely impaired innervation. CONCLUSIONS: PA
      deficiencies affect multiple aspects of taste bud development, including
      formation of the cranial ganglia and innervation to the posterior tongue.

PMID- 25997580
TI  - Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of
      adolescent rats.
AB  - Methylphenidate (MPH) is widely used as a "nootropic" agent and in the treatment
      of disorders of attention, and has been shown to modulate synaptic plasticity in
      vitro. Here we present in vivo evidence that this MPH-induced metaplasticity can
      last long after the end of treatment. MPH (0, 0.2, 1 and 5mg/kg) was administered
      daily to male rats from postnatal day 42 for 15 days. The animals were tested
      daily in a radial maze. Long-term potentiation (LTP), a marker of neural
      plasticity, was induced in vivo in the prefrontal cortex after 2-3h, 15-18 days
      or 5 months without treatment. The behavioral performance of the 1mg/kg group
      improved, while that of animals that had received 5mg/kg deteriorated. In the 1
      and 5mg/kg groups LTP induced 2-3h after the last MPH treatment was twice as
      large as in the controls. Further, 15-18 days after the last MPH administration,
      in groups receiving 1 and 5mg/kg, LTP was about fourfold higher than in controls.
      However, 5 months later, LTP in the 1mg/kg group was similar to controls and in
      the 5mg/kg group LTP could not be induced at all. No significant changes of LTP
      were seen in the low-dose group of animals (0.2mg/kg). Thus, firstly, doses of
      MPH that improve learning coincide approximately with those that augment LTP.
      Secondly, MPH-induced increases in LTP can last for several weeks, but these may
      disappear over longer periods or deteriorate at high doses. 

PMID- 25997582
TI  - Social stress effects on pigmentation and monoamines in Arctic charr.
AB  - Pigmentation often signals status and in general melanin-based pigmentation is
      indicative of aggression and stress resilience in vertebrates. This is evident in
      the salmonids Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus
      mykiss) where more melanin spotted individuals are more stress resilient.
      However, in the salmonid Arctic charr (Salvelinus alpinus) it seems as if it is
      carotenoid-based pigmentation that signals aggression and stress resilience. In
      our study, social stress effects on carotenoid-based spots, and behavioural and
      physiological stress responses were investigated. Socially stressed individuals
      have more spots, and behavioural stress responses were associated with spots.
      Some of the results concerning physiological stress responses, such as plasma
      cortisol levels and monoaminergic activity, are associated with spottiness.
      Further, the earlier proposed lateralization of spots, with left side connected
      to stress responsiveness and right side to aggression, is to some extent
      validated although not conclusively. In conclusion, this study provides further
      evidence that more stressed charr have more carotenoid spots, and for the first
      time monoaminergic activity is shown to be connected with carotenoid
      pigmentation. 

PMID- 25997581
TI  - Heart rate variability during carbachol-induced REM sleep and cataplexy.
AB  - The nucleus pontis oralis (NPO) exerts an executive control over REM sleep.
      Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a
      single microinjection of carbachol (a cholinergic agonist) into the NPO produces
      either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA). In
      order to study the central control of the heart rate variability (HRV) during
      sleep, we conducted polysomnographic and electrocardiogram recordings from
      chronically prepared cats during REMc, CA as well as during sleep and
      wakefulness. Subsequently, we performed statistical and spectral analyses of the
      HRV. The heart rate was greater during CA compared to REMc, NREM or REM sleep.
      Spectral analysis revealed that the low frequency band (LF) power was
      significantly higher during REM sleep in comparison to REMc and CA. Furthermore,
      we found that during CA there was a decrease in coupling between the RR intervals
      plot (tachogram) and respiratory activity. In contrast, compared to natural
      behavioral states, during REMc and CA there were no significant differences in
      the HRV based upon the standard deviation of normal RR intervals (SDNN) and the
      mean squared difference of successive intervals (rMSSD). In conclusion, there
      were differences in the HRV during naturally-occurring REM sleep compared to
      REMc. In addition, in spite of the same muscle atonia, the HRV was different
      during REMc and CA. Therefore, the neuronal network that controls the HRV during
      REM sleep can be dissociated from the one that generates the muscle atonia during
      this state. 

PMID- 25997584
TI  - Revisiting the cochlear and central mechanisms of tinnitus and therapeutic
      approaches.
AB  - This short review aims at revisiting some of the putative mechanisms of tinnitus.
      Cochlear-type tinnitus is suggested to result from aberrant activity generated
      before or at the cochlear nerve level. It is proposed that outer hair cells,
      through their role in regulating the endocochlear potential, can contribute to
      the enhancement of cochlear spontaneous activity. This hypothesis is attractive
      as it provides a possible explanation for cochlear tinnitus of different
      aetiologies, such as tinnitus produced by acute noise trauma, intense low
      frequency sounds, middle-ear dysfunction or temporomandibular joint disorders.
      Other mechanisms, namely an excitatory drift in the operating point of the inner
      hair cells and activation of NMDA receptors, are also briefly reported. Central
      type tinnitus is supposed to result from aberrant activity generated in auditory
      centres, i.e. in these patients, the tinnitus-related activity does not pre-exist
      in the cochlear nerve. A reduction in cochlear activity due to hearing loss is
      suggested to produce tinnitus-related plastic changes, namely cortical
      reorganisation, thalamic neuron hyperpolarisation, facilitation of non-auditory
      inputs and/or increase in central gain. These central changes can be associated
      with abnormal patterns of spontaneous activity in the auditory pathway, i.e.
      hyperactivity, hypersynchrony and/or oscillating activity. Therapeutic approaches
      aimed at reducing cochlear activity and/or tinnitus-related central changes are
      discussed.

PMID- 25997583
TI  - Biomonitoring of perfluorinated compounds in a drop of blood.
AB  - Biomonitoring of pollutants and their metabolites and derivatives using biofluids
      provides new opportunities for spatiotemporal assessment of human risks to
      environmental exposures. Perfluorinated compounds (PFCs) have been used widely in
      industry and pose significant environmental concerns due to their stability and
      bioaccumulation in humans and animals. However, current methods for extraction
      and measurement of PFCs require relatively large volumes (over one hundred
      microliters) of blood samples, and therefore, are not suitable for frequent blood
      sampling and longitudinal biomonitoring of PFCs. We have developed a new
      microassay, enabled by our silicon microfluidic chip platform, for analyzing PFCs
      in small volumes (less than five microliters) of blood. Our assay integrates on
      chip solid-phase extraction (SPE) with online nanoflow liquid chromatography
      electrospray ionization-mass spectrometry (nanoLC-ESI-MS) detection. We
      demonstrated high sample recovery, excellent interday and intraday accuracy and
      precision, and a limit of detection down to 50 femtogram of PFCs, in one
      microliter of human plasma. We validated our assay performance using pooled human
      plasma and NIST SRM 1950 samples. Our microfluidic chip-based assay may enable
      frequent longitudinal biomonitoring of PFCs and other environmental toxins using
      a finger prick of blood, thereby providing new insights into their
      bioaccumulation, bioavailability, and toxicity. 

PMID- 25997585
TI  - N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by
      inhibition of NF-kappaB translocation.
AB  - N-Stearoylethanolamine (NSE) is a minor lipid that belongs to the N
      Acylethanolamines family that mediates a wide range of biological processes. This
      study investigates the mechanisms of anti-inflammatory action of NSE on different
      model systems. Namely, we estimated the effect of NSE on inflammatory cytokines
      mRNA level (leukemia cells L1210), cytokines content (serum and LPS-stimulated
      macrophages) and nuclear translocation of NF-kappaB (peritoneal macrophages LPS
      stimulated and isolated from rats with obesity-induced insulin resistance). The
      results indicated that NSE dose-dependently inhibits the IL-1 and IL-6 mRNA level
      in L1210 cells. Furthermore, the NSE treatment triggered a normalization of serum
      TNF-alpha level in insulin resistant rats and a reduction of medium IL-1 level in
      LPS-activated peritoneal macrophages. These NSE's effects were associated with
      the inhibition of nuclear NF-kappaB translocation in rat peritoneal macrophages. 

PMID- 25997586
TI  - Acute cardiomyopathy precipitated by lithium: is there a direct toxic effect on
      cardiac myocytes?

PMID- 25997587
TI  - Alkylation of human hair keratin for tunable hydrogel erosion and drug delivery
      in tissue engineering applications.
AB  - Polymeric biomaterials that provide a matrix for cell attachment and
      proliferation while achieving delivery of therapeutic agents are an important
      component of tissue engineering and regenerative medicine strategies. Keratins
      are a class of proteins that have received attention for numerous tissue
      engineering applications because, like other natural polymers, they promote
      favorable cell interactions and have non-toxic degradation products. Keratins can
      be extracted from various sources including human hair, and they are
      characterized by a high percentage of cysteine residues. Thiol groups on
      reductively extracted keratin (kerateine) form disulfide bonds, providing a more
      stable cross-linked hydrogel network than oxidatively extracted keratin
      (keratose) that cannot form disulfide crosslinks. We hypothesized that an
      iodoacetamide alkylation (or "capping") of cysteine thiol groups on the kerateine
      form of keratin could be used as a simple method to modulate the levels of
      disulfide crosslinking in keratin hydrogels, providing tunable rates of gel
      erosion and therapeutic agent release. After alkylation, the alkylated kerateines
      still formed hydrogels and the alkylation led to changes in the mechanical and
      visco-elastic properties of the materials consistent with loss of disulfide
      crosslinking. The alkylated kerateines did not lead to toxicity in MC3T3-E1 pre
      osteoblasts. These cells adhered to keratin at levels comparable to fibronectin
      and greater than collagen. Alkylated kerateine gels eroded more rapidly than non
      alkylated kerateine and this control over erosion led to tunable rates of
      delivery of rhBMP-2, rhIGF-1, and ciprofloxacin. These results demonstrate that
      alkylation of kerateine cysteine residues provides a cell-compatible approach to
      tune rates of hydrogel erosion and therapeutic agent release within the context
      of a naturally-derived polymeric system. 

PMID- 25997589
TI  - Treatments for delusional disorder.
AB  - BACKGROUND: Delusional disorder is commonly considered to be difficult to treat.
      Antipsychotic medications are frequently used and there is growing interest in a
      potential role for psychological therapies such as cognitive behavioural therapy
      (CBT) in the treatment of delusional disorder. OBJECTIVES: To evaluate the
      effectiveness of medication (antipsychotic medication, antidepressants, mood
      stabilisers) and psychotherapy, in comparison with placebo in delusional
      disorder. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials
      Register (28 February 2012). SELECTION CRITERIA: Relevant randomised controlled
      trials (RCTs) investigating treatments in delusional disorder. DATA COLLECTION
      AND ANALYSIS: All review authors extracted data independently for the one
      eligible trial. For dichotomous data we calculated risk ratios (RR) and their 95%
      confidence intervals (CI) on an intention-to-treat basis with a fixed-effect
      model. Where possible, we calculated illustrative comparative risks for primary
      outcomes. For continuous data, we calculated mean differences (MD), again with a
      fixed-effect model. We assessed the risk of bias of the included study and used
      the GRADE approach to rate the quality of the evidence. MAIN RESULTS: Only one
      randomised trial met our inclusion criteria, despite our initial search yielding
      141 citations. This was a small study, with 17 people completing a trial
      comparing CBT to an attention placebo (supportive psychotherapy) for people with
      delusional disorder. Most participants were already taking medication and this
      was continued during the trial. We were not able to include any randomised trials
      on medications of any type due to poor data reporting, which left us with no
      usable data for these trials. For the included study, usable data were limited,
      risk of bias varied and the numbers involved were small, making interpretation of
      data difficult. In particular there were no data on outcomes such as global state
      and behaviour, nor any information on possible adverse effects.A positive effect
      for CBT was found for social self esteem using the Social Self-Esteem Inventory
      (1 RCT, n = 17, MD 30.5, CI 7.51 to 53.49, very low quality evidence), however
      this is only a measure of self worth in social situations and may thus not be
      well correlated to social function. More people left the study early if they were
      in the supportive psychotherapy group with 6/12 leaving early compared to 1/6
      from the CBT group, but the difference was not significant (1 RCT, n = 17, RR
      0.17, CI 0.02 to 1.18, moderate quality evidence). For mental state outcomes the
      results were skewed making interpretation difficult, especially given the small
      sample. AUTHORS' CONCLUSIONS: Despite international recognition of this disorder
      in psychiatric classification systems such as ICD-10 and DSM-5, there is a
      paucity of high quality randomised trials on delusional disorder. There is
      currently insufficient evidence to make evidence-based recommendations for
      treatments of any type for people with delusional disorder. The limited evidence
      that we found is not generalisable to the population of people with delusional
      disorder. Until further evidence is found, it seems reasonable to offer
      treatments which have efficacy in other psychotic disorders. Further research is
      needed in this area and could be enhanced in two ways: firstly, by conducting
      randomised trials specifically for people with delusional disorder and, secondly,
      by high quality reporting of results for people with delusional disorder who are
      often recruited into larger studies for people with a variety of psychoses.

PMID- 25997588
TI  - A novel Sarcocystis neurona genotype XIII is associated with severe encephalitis
      in an unexpectedly broad range of marine mammals from the northeastern Pacific
      Ocean.
AB  - Sarcocystis neurona is an important cause of protozoal encephalitis among marine
      mammals in the northeastern Pacific Ocean. To characterise the genetic type of S.
      neurona in this region, samples from 227 stranded marine mammals, most with
      clinical or pathological evidence of protozoal disease, were tested for the
      presence of coccidian parasites using a nested PCR assay. The frequency of S.
      neurona infection was 60% (136/227) among pinnipeds and cetaceans, including
      seven marine mammal species not previously known to be susceptible to infection
      by this parasite. Eight S. neurona fetal infections identified this coccidian
      parasite as capable of being transmitted transplacentally. Thirty-seven S.
      neurona-positive samples were multilocus sequence genotyped using three genetic
      markers: SnSAG1-5-6, SnSAG3 and SnSAG4. A novel genotype, referred to as Type
      XIII within the S. neurona population genetic structure, has emerged recently in
      the northeastern Pacific Ocean and is significantly associated with an increased
      severity of protozoal encephalitis and mortality among multiple stranded marine
      mammal species. 

PMID- 25997590
TI  - Nitrogen-doped Graphene-Supported Transition-metals Carbide Electrocatalysts for
      Oxygen Reduction Reaction.
AB  - A novel and facile two-step strategy has been designed to prepare high
      performance bi-transition-metals (Fe- and Mo-) carbide supported on nitrogen
      doped graphene (FeMo-NG) as electrocatalysts for oxygen reduction reactions
      (ORR). The as-synthesized FeMo carbide -NG catalysts exhibit excellent
      electrocatalytic activities for ORR in alkaline solution, with high onset
      potential (-0.09 V vs. saturated KCl Ag/AgCl), nearly four electron transfer
      number (nearly 4) and high kinetic-limiting current density (up to 3.5 mA cm(-2)
      at -0.8 V vs. Ag/AgCl). Furthermore, FeMo carbide -NG composites show good cycle
      stability and much better toxicity tolerance durability than the commercial Pt/C
      catalyst, paving their application in high-performance fuel cell and lithium-air
      batteries.

PMID- 25997591
TI  - The role of agri-environment schemes in conservation and environmental
      management.
AB  - Over half of the European landscape is under agricultural management and has been
      for millennia. Many species and ecosystems of conservation concern in Europe
      depend on agricultural management and are showing ongoing declines. Agri
      environment schemes (AES) are designed partly to address this. They are a major
      source of nature conservation funding within the European Union (EU) and the
      highest conservation expenditure in Europe. We reviewed the structure of current
      AES across Europe. Since a 2003 review questioned the overall effectiveness of
      AES for biodiversity, there has been a plethora of case studies and meta-analyses
      examining their effectiveness. Most syntheses demonstrate general increases in
      farmland biodiversity in response to AES, with the size of the effect depending
      on the structure and management of the surrounding landscape. This is important
      in the light of successive EU enlargement and ongoing reforms of AES. We examined
      the change in effect size over time by merging the data sets of 3 recent meta
      analyses and found that schemes implemented after revision of the EU's agri
      environmental programs in 2007 were not more effective than schemes implemented
      before revision. Furthermore, schemes aimed at areas out of production (such as
      field margins and hedgerows) are more effective at enhancing species richness
      than those aimed at productive areas (such as arable crops or grasslands).
      Outstanding research questions include whether AES enhance ecosystem services,
      whether they are more effective in agriculturally marginal areas than in
      intensively farmed areas, whether they are more or less cost-effective for
      farmland biodiversity than protected areas, and how much their effectiveness is
      influenced by farmer training and advice? The general lesson from the European
      experience is that AES can be effective for conserving wildlife on farmland, but
      they are expensive and need to be carefully designed and targeted. 

PMID- 25997593
TI  - Rituximab in Thrombotic Thrombocytopenic Purpura: Medical and Financial Benefits.

PMID- 25997592
TI  - Towards a standardized Rapid Ecosystem Function Assessment (REFA).
AB  - Quantifying ecosystem functioning is important for both fundamental and applied
      ecological research. However, there is currently a gap between the data available
      and the data needed to address topical questions, such as the drivers of
      functioning in different ecosystems under global change or the best management to
      sustain provisioning of ecosystem functions and services. Here, we identify a set
      of important functions and propose a Rapid Ecosystem Function Assessment (REFA).
      The proposed methods were specifically selected to be low-tech, easy to use,
      repeatable, and cost efficient. Thus, REFA enables standardized and comparable
      measurements of proxies for these functions that can be used at a large scale
      within and across studies. Adopting REFA can help to close the identified
      ecosystem functioning data gap. 

PMID- 25997594
TI  - Castration impairs erectile organ structure and function by inhibiting autophagy
      and promoting apoptosis of corpus cavernosum smooth muscle cells in rats.
AB  - OBJECTIVE: The aim of this study was to determine the changes and underlying
      mechanisms of erectile organ structure and function in castrated rats. In
      addition, the regulatory effects of an androgen on autophagy and apoptosis in
      corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect
      of androgen on the BECN 1-Bcl-2 interaction, were investigated. METHODS: Male
      Sprague-Dawley rats were divided into three groups (30/group): control group,
      castration group, and castration with testosterone supplementation group. The
      erectile function was examined both in vivo and in vitro, by electric stimulation
      of the cavernous nerve and corpus cavernosum strip bath test, respectively.
      Transmission electron microscopy, TUNEL assay, Masson's trichrome staining,
      immunohistochemistry, and western blotting were performed to determine the levels
      of autophagy and apoptosis, and the structural changes in corpus cavernosum.
      RESULTS: Compared with control group, the castration group showed (1) lower
      erectile function: lower intracavernosal pressure/mean arterial pressure ratio,
      lower systolic and diastolic capability of corporal strips, and reduced
      expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth
      muscle/collagen ratio, lower expression of alpha-SMA, and higher expression of
      TGF-beta1; (3) inhibited autophagy: decreased autophagosomes, lower expressions
      of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and
      decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the
      effects of castration. CONCLUSIONS: Castration attenuates erectile function and
      induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of
      CCSMCs in rats. Therefore, our study highlights the important role of androgens
      in maintaining the integrity of the structure and function of corpus cavernosum
      in rats through counter-regulation of autophagy and apoptosis, mainly by
      regulating BECN 1-Bcl-2 interaction.

PMID- 25997596
TI  - Does Autism Diagnosis Age or Symptom Severity Differ Among Children According to
      Whether Assisted Reproductive Technology was Used to Achieve Pregnancy?
AB  - Previous studies report associations between conception with assisted
      reproductive technology (ART) and autism. Whether these associations reflect an
      ascertainment or biologic effect is undetermined. We assessed diagnosis age and
      initial autism symptom severity among >30,000 children with autism from a linkage
      study of California Department of Developmental Services records, birth records,
      and the National ART Surveillance System. Median diagnosis age and symptom
      severity levels were significantly lower for ART-conceived than non-ART-conceived
      children. After adjustment for differences in the socio-demographic profiles of
      the two groups, the diagnosis age differentials were greatly attenuated and there
      were no differences in autism symptomatology. Thus, ascertainment issues related
      to SES, not ART per se, are likely the driving influence of the differences we
      initially observed. 

PMID- 25997595
TI  - Right versus left retroperitoneoscopic living-donor nephrectomy.
AB  - PURPOSE: To compare the safety and efficacy of right-side and left-side
      retroperitoneoscopic donor nephrectomy (RDN) using our hybrid technique. METHODS:
      We retrospectively reviewed the data obtained from 151 consecutive patients who
      underwent RDN between May 2005 and July 2013. Right and left nephrectomies were
      performed in 87 and 64 patients, respectively. We compared these two groups with
      respect to donors' intraoperative parameters, postoperative outcomes, and
      recipients' outcomes. RESULTS: There were no significant differences between the
      two groups regarding donor blood loss, warm ischemia time, donor postoperative
      creatinine levels, donor postoperative length of hospital stay, recipient
      creatinine levels at 1 year after transplantation, and 1-year graft survival rate
      after transplantation. The time required for graft extraction and overall
      operative time were significantly shorter in the right RDN group than in the left
      RDN group (152 vs. 168 min, P = 0.016; 175 vs. 195 min, P = 0.0059). Only one
      case in the right nephrectomy group required open conversion because of
      uncontrollable bleeding from the inferior vena cava. CONCLUSION: Although larger
      sample sizes would be required to evaluate postoperative complication rate, these
      results indicate that both the right and left RDN could be performed with similar
      donor and recipient outcomes.

PMID- 25997597
TI  - Stimulus over-selectivity and extinction-induced recovery of performance as a
      product of intellectual impairment and autism severity.
AB  - The current experiment investigated the extent to which three variables (autism
      severity, nonverbal intellectual functioning, and verbal intellectual
      functioning) are associated with over-selective responding in a group of children
      with Autism Spectrum Disorder. This paper also analyzed the association of these
      three variables with the recovery of responding to a previously under-selected
      stimulus following extinction of the previously over-selected stimulus. The
      results demonstrated that participants showed over-selectivity, and demonstrated
      that extinction of the over-selected stimulus led to recovery of responding to
      the previously under-selected stimulus. For both over-selectivity, and recovery
      from over-selectivity, verbal functioning appeared to predict the effects most
      strongly, with greater over-selectivity in the lower functioning individuals, and
      greater recovery in the higher functioning individuals. 

PMID- 25997598
TI  - Visual Hybrid Development Learning System (VHDLS) framework for children with
      autism.
AB  - The effect of education on children with autism serves as a relative cure for
      their deficits. As a result of this, they require special techniques to gain
      their attention and interest in learning as compared to typical children. Several
      studies have shown that these children are visual learners. In this study, we
      proposed a Visual Hybrid Development Learning System (VHDLS) framework that is
      based on an instructional design model, multimedia cognitive learning theory, and
      learning style in order to guide software developers in developing learning
      systems for children with autism. The results from this study showed that the
      attention of children with autism increased more with the proposed VHDLS
      framework. 

PMID- 25997599
TI  - A Novel Terminator Primer and Enhancer Reagents for Direct Expression of PCR
      Amplified Genes in Mammalian Cells.
AB  - Escherichia coli plasmids are commonly used for gene expression experiments in
      mammalian cells, while PCR-amplified DNAs are rarely used even though PCR is a
      much faster and easier method to construct recombinant DNAs. One difficulty may
      be the limited amount of DNA produced by PCR. For direct utilization of PCR
      amplified DNA in transfection experiments, efficient transfection with a smaller
      amount of DNA should be attained. For this purpose, we investigated two enhancer
      reagents, polyethylene glycol and tRNA, for a chemical transfection method. The
      addition of the enhancers to a commercial transfection reagent individually and
      synergistically exhibited higher transfection efficiency applicable for several
      mammalian cell culture lines in a 96-well plate. By taking advantage of a simple
      transfection procedure using PCR-amplified DNA, SV40 and rabbit beta-globin
      terminator lengths were minimized. The terminator length is short enough to
      design in oligonucleotides; thus, terminator primers can be used for the
      construction and analysis of numerous mutations, deletions, insertions, and tag
      fusions at the 3'-terminus of any gene. The PCR-mediated gene manipulation with
      the terminator primers will transform gene expression by allowing for extremely
      simple and high-throughput experiments with small-scale, multi-well, and
      mammalian cell cultures. 

PMID- 25997600
TI  - Dissecting the role of aberrant DNA methylation in human leukaemia.
AB  - Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by
      the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion
      oncogene. However, many molecular mechanisms of the disease progression still
      remain poorly understood. A growing body of evidence suggests that the epigenetic
      abnormalities are involved in tyrosine kinase resistance in CML, leading to
      leukaemic clone escape and disease propagation. Here we show that, by applying
      cellular reprogramming to primary CML cells, aberrant DNA methylation contributes
      to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we
      demonstrate that a single oncogenic lesion triggers DNA methylation changes,
      which in turn act as a precipitating event in leukaemia progression. 

PMID- 25997601
TI  - Staged venous thromboemolic events prophylaxis with low-molecular-weight heparin
      followed by aspirin is safe and effective after arthroplasty.
AB  - BACKGROUND: The rate of fatal pulmonary embolism (PE) following hip and knee
      arthroplasty has remained unchanged despite the use of low-molecular-weight
      heparin (LMWH) and oral antithrombotic agents. Concerns regarding bleeding and
      wound complications resulted in the introduction of a staged chemoprophylaxis
      protocol at our institution in 2002. We hypothesized that staged chemoprophylaxis
      using LMWH in hospital followed by aspirin after discharge was safe and effective
      for the prevention of venous thromboembolic events (VTE). METHODS: Data were
      retrospectively collected on all patients undergoing hip and knee arthroplasty
      between 2002 and 2012. For VTE prophylaxis, LMWH was administered to all patients
      following surgery until discharge. Aspirin was prescribed from discharge until 6
      weeks following surgery. Complications were recorded in a database. Patients
      suspected of having a VTE were investigated with bilateral lower limb duplex
      ultrasound and computerized tomography-pulmonary angiogram. RESULTS: The 11-year
      results of this protocol used in 9035 patients with a mean age 62 years (range 20
      95) and follow-up at 6 weeks demonstrate an overall symptomatic VTE rate of 2.55%
      and overall PE rate of 1.28%. The overall fatal PE rate is 0.03%
      (unicompartmental knee arthroplasty 0.07-0.96%, total knee arthroplasty 0.19% and
      total hip arthroplasty 0%) and the all-cause mortality is 0.07%. The wound
      complication rate is low. CONCLUSION: Staged chemoprophylaxis using LMWH followed
      by aspirin is a safe and effective thromboprophylactic regime that is associated
      with a very low rate of fatal PE and all-cause mortality.

PMID- 25997602
TI  - Diagnostic value of preoperative CT scan to stratify colon cancer for neoadjuvant
      therapy.
AB  - BACKGROUND AND OBJECTIVE: Neoadjuvant therapy could improve oncological outcome
      of patients suffering from colon cancer. An accurate staging method is needed to
      define suitable patients. The aim of this retrospective study was to validate the
      value of CT for identifying patients with local advanced (T3/4) or nodal-positive
      colon cancer. METHODS AND MATERIAL: Preoperative abdominal CT scans of 210
      patients with colon cancer were evaluated by two radiologists independently for
      the T stage and N stage. Results were compared to pathology. Patients were
      stratified according to the guidelines for rectal cancer into patients with low
      risk (T0/1/2 and N0) or high risk (T3/4 or N+). RESULTS: Inter-observer
      correlation was high with over 90 %. Overall sensitivity T stage was 93.0 % and
      for N stage 76.9 %. Using CT scan to identify local advanced (T3/4 or N+) tumors,
      the consensus sensitivity was 94.9 %, the specificity 53.6 %, the positive
      predictive value (PPV) 92.8 %, and the negative predictive value (NPV) 62.5 %.
      CONCLUSION: Computer tomography represents an effective tool for identifying
      patients with colon cancer suitable for neoadjuvant therapy according to the
      guidelines for rectal cancer.

PMID- 25997603
TI  - Study of the competitive mechanisms of cyclohexane dehydrogenation by gas-phase
      Ni2(+) cationic dimer: one-face dehydrogenation versus flip dehydrogenation.
AB  - The mechanism of cyclohexane dehydrogenation catalyzed by the cationic dimer Ni2
      (+) has been investigated at the B3LYP level of density functional theory. The
      first dehydrogenation occurs readily (it is exothermic by 30 kcal/mol), whereas
      the second and third dehydrogenations show weaker exothermicity than the first
      (23 and 21 kcal/mol, respectively). These three hydrogenations corresponding to
      the total dehydrogenation of one face of cyclohexane mainly proceed in the
      doublet state due to the presence of significant minimum-energy crossing points
      (MECPs). In addition, because the elimination of non-negligible amounts of
      [H2,2D2] and [2H2,D2] in this reaction was also observed in a previous
      experiment, we calculated a flip mechanism which would yield results that agree
      with those experimental results. This flip process includes two MECPs, meaning
      that the reaction mainly proceeds along the doublet potential energy surface but
      finishes in the quartet state. The rate-limiting step ((2)IM9 -> (2)TS9/10 ->
      (2)IM10) of the flip process is endothermic by 3 kcal/mol and the barrier to this
      step is 33 kcal/mol. Our calculations indicate that one-face dehydrogenation is a
      more favorable channel than the flip one. We excluded the possibility that
      eliminations of [H2,2D2] or [D2,2H2] could proceed through a mechanism involving
      Ni2 (+) dissociation, or that [H-D] scrambling could occur through (2)TS11/13
      ((4)TS12/15), due to the large amounts of energy required. In the dissociation of
      (2)IM19, (2)[(H2)Ni2(C6H6)](+), a molecule of hydrogen first dissociates, leaving
      a final product of (2)[Ni2(C6H6)](+). Neither C6H6 nor (H2)Ni2 (+) can easily
      dissociate from (2)IM19 due to pi backdonation. 

PMID- 25997604
TI  - Treat the treatable: a comprehensive and optimistic approach to treating
      psychiatric violence.

PMID- 25997605
TI  - Serotonin and impulsive aggression.
AB  - Aggression is a behavior with evolutionary origins, but is often both destructive
      and maladaptive in today's society. Research over the past several decades has
      confirmed the involvement of neurotransmitter function in aggressive behavior.
      This research has centered around the "serotonin hypothesis." As this literature
      continues to grow, guided by pre-clinical research and aided by the application
      of increasingly sophisticated neuroimaging methodology, a more complex picture
      has emerged. As current pharmacological and therapeutic interventions are
      effective but imperfect, it is hoped that new insights into the neurobiology of
      aggression will reveal novel avenues for treatment of this destructive and costly
      behavior. 

PMID- 25997606
TI  - Risk reduction treatment of psychopathy and applications to mentally disordered
      offenders.
AB  - Therapeutic nihilism on treating psychopathy is widespread and is largely based
      on many outdated and poorly designed studies. Important recent advances have been
      made in assessing psychopathy and recidivism risks, as well as in offender
      rehabilitation to reduce reoffending, all of which are now well supported by a
      considerable literature based on credible empirical research. A 2-component model
      to guide risk reduction treatment of psychopathy has been proposed based on the
      integration of key points from the 3 bodies of literature. Treatment programs in
      line with the model have been in operation, and the results of early outcome
      evaluations are encouraging. Important advances also have been made in
      understanding the possible etiology of mentally disordered offenders with
      schizophrenia and history of criminality and violence, some with significant
      features of psychopathy. This article presents a review of recent research on
      risk reduction treatment of psychopathy with the additional aim to extend the
      research to the treatment of mentally disordered offenders with schizophrenia,
      violence, and psychopathy. 

PMID- 25997607
TI  - Aortic Size Distribution in the General Population: Explaining the Size Paradox
      in Aortic Dissection.
AB  - BACKGROUND: Current guidelines recommend a diameter of 5-5.5 cm as the threshold
      for surgery on the ascending aorta. However, a study from the International
      Registry of Acute Aortic Dissection showed that nearly 60% occurred at <5.5 cm
      (the 'aortic size paradox')--leading to a debate whether the size threshold
      should be lowered. However, the study showing dissection at small size had no
      knowledge of the population at risk. Herein, we aim to calculate the relative
      risk of aortic dissection at sizes<5.5 cm by analyzing both the number of
      occurring dissections (numerator) and the population at risk at each aortic size
      (denominator). METHODS: Using a publicly available database of 3,573 multiethnic
      subjects (46% male, mean age 60.7 years) from the general population, we plotted
      a distribution curve of ascending aortic size (by magnetic resonance imaging).
      The relative risk of aortic dissection was calculated by dividing the proportion
      of dissections occurring at each size (numerator) by the proportion of aortas of
      that same size in the general population (denominator). RESULTS: The mean
      ascending aortic diameter of the reference population was 3.2 cm (+/-0.4 cm). The
      largest diameter was 4.9 cm in women and 5.0 cm in men. The proportion of
      subjects with an aorta <3.5 cm was 79.2%, that of subjects with 3.5-3.9 cm was
      18.0%, that of subjects with 4.0-4.4 cm was 2.6%, and that of subjects with >=4.5
      cm was 0.22%. The relative risk of dissection in those categories was found to be
      0.055, 2.5, 4.9, and 346.8, respectively. Patients with an aorta>=4.5 cm were
      6,305 times more likely to suffer aortic dissection than those with an aorta<3.5
      cm. CONCLUSIONS: The normal aorta is deceptively small, most commonly <3.5 cm.
      The aortic size paradox is a byproduct of the very large number of patients in
      small size ranges. This study fully supports current recommendations for surgical
      intervention at 5-5.5 cm.

PMID- 25997608
TI  - [Epidemiology of Ebola virus disease and of other highly contagious, life
      threatening diseases with low incidence in Germany].
AB  - Apart from sporadic exported cases, the occurrence of Ebola, Marburg and Lassa
      virus diseases is limited to the African continent. Crimean-Congo Hemorrhagic
      Fever occurs in Southeastern Europe but, so far, not in Germany. Other
      hemorrhagic fever disease-viruses occur in distinct regions in South America.
      Pulmonary plague is the bacterial infectious disease with the most contagious and
      lethal course and it is endemic to Madagascar and East Africa, but also occurs in
      other countries (e.g. India, USA). Monkey pox epidemics have occurred in remote
      areas of the Congo Basin. Such outbreaks could potentially become more common
      with the discontinuation of the cross-protective smallpox vaccination. The Severe
      Acute Respiratory Syndrome (SARS) that emerged in 2002/2003 is another pathogen
      with significant epidemic potential. Typical for these diseases is a natural
      circulation between reservoir animals in remote areas. Sporadic transmission to
      humans can occur through contact with an infected animal. Subsequent human-to
      human transmission can lead to epidemics, such as the current outbreak of Ebola
      virus disease in West Africa. 

PMID- 25997609
TI  - A practical deca-gram scale ring expansion of (R)-(-)-carvone to (R)-(+)-3-methyl
      6-isopropenyl-cyclohept-3-enone-1.
AB  - A route to enantiopure (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1, an
      intermediate for terpenoids, has been developed and includes a highly chemo- and
      regioselective Tiffeneau-Demjanov reaction. Starting from readily available (R)-(
      )-carvone, this robust sequence is available on a deca-gram scale and uses flow
      chemistry for the initial epoxidation reaction. The stereochemistry of the
      addition of two nucleophiles to the carbonyl group of (R)-(-)-carvone has been
      determined by X-ray diffraction studies and chemical correlation. 

PMID- 25997611
TI  - Interaction-induced singular Fermi surface in a high-temperature oxypnictide
      superconductor.
AB  - In the family of iron-based superconductors, LaFeAsO-type materials possess the
      simplest electronic structure due to their pronounced two-dimensionality. And yet
      they host superconductivity with the highest transition temperature Tc ~ 55K.
      Early theoretical predictions of their electronic structure revealed multiple
      large circular portions of the Fermi surface with a very good geometrical overlap
      (nesting), believed to enhance the pairing interaction and thus
      superconductivity. The prevalence of such large circular features in the Fermi
      surface has since been associated with many other iron-based compounds and has
      grown to be generally accepted in the field. In this work we show that a
      prototypical compound of the 1111-type, SmFe(0.92)Co(0.08)AsO , is at odds with
      this description and possesses a distinctly different Fermi surface, which
      consists of two singular constructs formed by the edges of several bands, pulled
      to the Fermi level from the depths of the theoretically predicted band structure
      by strong electronic interactions. Such singularities dramatically affect the low
      energy electronic properties of the material, including superconductivity. We
      further argue that occurrence of these singularities correlates with the maximum
      superconducting transition temperature attainable in each material class over the
      entire family of iron-based superconductors.

PMID- 25997610
TI  - Identification of diagnostic markers in colorectal cancer via integrative
      epigenomics and genomics data.
AB  - Apart from genetic mutations, epigenetic alteration is a common phenomenon that
      contributes to neoplastic transformation in colorectal cancer. Transcriptional
      silencing of tumor-suppressor genes without changes in the DNA sequence is
      explained by the existence of promoter hypermethylation. To test this hypothesis,
      we integrated the epigenome and transcriptome data from a similar set of
      colorectal tissue samples. Methylation profiling was performed using the Illumina
      InfiniumHumanMethylation27 BeadChip on 55 paired cancer and adjacent normal
      epithelial cells. Fifteen of the 55 paired tissues were used for gene expression
      profiling using the Affymetrix GeneChip Human Gene 1.0 ST array. Validation was
      carried out on 150 colorectal tissues using the methylation-specific multiplex
      ligation-dependent probe amplification (MS-MLPA) technique. PCA and supervised
      hierarchical clustering in the two microarray datasets showed good separation
      between cancer and normal samples. Significant genes from the two analyses were
      obtained based on a >=2-fold change and a false discovery rate (FDR) p-value of
      <0.05. We identified 1,081 differentially hypermethylated CpG sites and 36
      hypomethylated CpG sites. We also found 709 upregulated and 699 downregulated
      genes from the gene expression profiling. A comparison of the two datasets
      revealed 32 overlapping genes with 27 being hypermethylated with downregulated
      expression and 4 hypermethylated with upregulated expression. One gene was found
      to be hypomethylated and downregulated. The most enriched molecular pathway
      identified was cell adhesion molecules that involved 4 overlapped genes, JAM2,
      NCAM1, ITGA8 and CNTN1. In the present study, we successfully identified a group
      of genes that showed methylation and gene expression changes in well-defined
      colorectal cancer tissues with high purity. The integrated analysis gives
      additional insight regarding the regulation of colorectal cancer-associated genes
      and their underlying mechanisms that contribute to colorectal carcinogenesis.

PMID- 25997612
TI  - Role of hypoxia-inducible factor-1alpha and CD146 in epidermal growth factor
      receptor-mediated angiogenesis in salivary gland adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma (AdCC) of the salivary gland in the head and neck is
      characterized by indolent yet persistent growth, multiple local recurrences and
      early hematogenous metastasis. Considering the possible association between the
      epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in
      various types of cancer and the overexpression of EGFR in AdCC, it is reasonable
      to examine the correlation between angiogenesis and the EGFR signaling pathway in
      this carcinoma. In the present study, the expression of EGFR, CD31, CD146 and
      hypoxia-inducible factor-1alpha (HIF-1alpha) were evaluated by
      immunohistochemical staining with tissue microarray containing normal salivary
      gland (NSG), pleomorphic adenoma (PMA) and AdCC tissues. Pearson's correlation
      coefficient was conducted to demonstrate the correlation between EGFR, CD31,
      CD146 and HIF-1alpha. To determine their similarity and intimacy, hierarchical
      analysis was performed with Cluster 3.0 and then visualized using TreeView
      software. Immunohistochemical results of tissue microarrays were quantified,
      revealing that the expression of EGFR, CD146 and HIF-1alpha increased in AdCC
      compared with in PMA and NSG tissues. The association between the expression of
      EGFR and CD31 was significant and positive. The expression of CD146 and HIF
      1alpha was positively correlated with EGFR and CD31, respectively. These findings
      suggest that the EGFR signaling pathway has a vital role in AdCC progression and
      may be associated with HIF-1alpha-mediated angiogenesis. These results may
      enhance our understanding of the mechanism underlying AdCC progression and
      provide potential clinical therapeutic strategies based on the inhibition of
      EGFR.

PMID- 25997613
TI  - Trematode diversity in the freshwater snail Bithynia siamensis goniomphalos sensu
      lato from Thailand and Lao PDR.
AB  - In order to obtain a comprehensive understanding of trematode diversity in
      Bithynia siamensis goniomphalos sensu lato, the first intermediate host of the
      liver fluke Opisthorchis viverrini s.l., the prevalence of larval trematode
      species was investigated in different localities in Thailand and Lao People's
      Democratic Republic (Lao PDR). In Thailand, snail samples were collected from 29
      localities in the nine provinces: Buri Ram, Surin, Chaiya Phum, Maha Sarakham,
      Khon Kaen, Kalasin, Mukdahan, Sakon Nakhon and Nakhon Phanom. In Lao PDR, snail
      samples were collected from 21 localities in Vientiane Province and six
      localities in Savannakhet Province. Snails were identified by standard
      morphological criteria and then examined for trematode infection using the
      cercarial shedding method. Twenty different types of cercariae were detected and
      identified, based on morphological criteria. Virgulate type 1 emerged as the most
      common cercaria, with an average prevalence of 10.90% (range 0.26-54.22%) in
      Thailand and 6.58% (range 1.15-89.77%) in Lao PDR. Opisthorchis viverrini s.l.
      cercariae were the fourth most common in Thailand, with an average prevalence of
      1.59% (0.15-6.93), while in Lao PDR their prevalence was 0.96% (0.08-8.37). The
      high diversity of trematode cercariae observed in this study indicates that B. s.
      goniomphalos s.l. is highly susceptible to infection with a variety of trematode
      species. However, the role of non-opisthorchiid trematodes as fish-borne
      parasites in human health is not fully known and further molecular identification
      is required. 

PMID- 25997615
TI  - Emerging Role of Probiotics in the Management of Helicobacter pylori Infection:
      Histopathologic Perspectives.
AB  - BACKGROUND: There is growing evidence from preclinical and clinical studies that
      emphasizes the efficacy of probiotics in the management of Helicobacter (H)
      pylori infection; it increased the eradication rate, improved patient clinical
      manifestations and lowered treatment associated side effects. AIM: In this review
      we documented the potential ability of probiotics to ameliorate H. pylori induced
      histological features. MATERIALS AND METHODS: We searched the available
      literature for full length articles focusing the role of probiotics on H. pylori
      induced gastritis from histologic perspectives. RESULTS: Probiotics lowered H.
      pylori density at the luminal side of epithelium, improved histological
      inflammatory and activity scores both in the gastric corpus and antrum. This
      effect persists for long period of time after discontinuation of probiotic
      supplementation and this is probably through an immune mechanism. CONCLUSIONS:
      The current evidence support the promising role of probiotics in improving H.
      pylori induced histopathological features both in gastric antrum and corpus and
      for long periods of time. Because increased density of H. pylori on the gastric
      mucosa is linked to more severe gastritis and increased incidence of peptic
      ulcers, we can infer that a reduction of the density might help to decrease the
      risk of developing pathologies, probably the progression toward atrophic
      gastritis and gastric adenocarcinoma. These effects together with improving the
      H. pylori eradication rates and amelioration of treatment related side effects
      might open the door for probiotics to be added to H. pylori eradication regimens.

PMID- 25997614
TI  - A novel insA2933 causes premature termination of translation and is accompanied
      by overexpression of truncated androgen receptor gene in a patient with complete
      androgen insensitivity syndrome.
AB  - A patient with a female phenotype, 46,XY karyotype, and a diagnosis of complete
      androgen insensitivity syndrome (CAIS) was examined. Her mother and three 46,XX
      sisters were also included in the study. Sequence analysis of the androgen
      receptor gene (AR) revealed a novel A2933 insertion that alters the Tyr codon to
      a termination codon (Y857X), resulting in a truncated form of the receptor.
      Computer simulation revealed major conformational changes in the hydrophobic
      pocket that accommodates the hormone. An insA2933 results in a truncated receptor
      incapable of binding the ligand and is responsible for the clinical symptoms of
      CAIS in the patient. The levels of the AR transcript in peripheral blood
      leukocytes were higher in the patient than in her heterozygous mother and her
      heterozygous sister, as well as in the two healthy sisters. It is hypothesized
      that elevated levels of the AR transcript in the patient might be caused by the
      inability of the truncated receptor to react with IFI-16, which functions in
      complex with AR to inhibit the expression of the AR gene. 

PMID- 25997616
TI  - Let-7i inhibits the malignant phenotype of osteosarcoma cells by targeting Aurora
      B.
AB  - Our previous study indicated that Aurora-B is involved in osteosarcoma (OS) cell
      invasion and metastasis; however, the mechanism underlying Aurora-B
      overexpression in OS remains unknown. In the present study, significantly
      downregulated let-7i expression in OS tissues and OS cells was observed compared
      with that in normal adjacent tumorous tissues and human osteoblast cell lines.
      Bioinformatic predictions have revealed a conserved binding site in a microRNA
      locus on Aurora-B, suggesting the potential of let-7i targeting the Aurora-B
      gene. To validate this, a luciferase reporter assay was performed on OS cells.
      The results indicated that Aurora-B is a likely to be a direct target negatively
      regulated by let-7i. The expression of let-7i in OS cells was restored by
      infection with let-7i mimics. Results revealed that Aurora-B mRNA and protein
      expression levels were significantly decreased. Furthermore, the proliferation,
      migration and invasion abilities of OS cells were significantly suppressed by
      infection with let-7i mimics. Notably, the inhibitory effect of silencing Aurora
      B by LV-shAurora-B on cell proliferation, migratory and invasive ability was
      significantly lower than that by let-7i mimics, which indicated that let-7i
      inhibits cell malignant phenotypes partially by targeting Aurora-B in OS cells.
      All data suggested that let-7i may be a novel potential target for OS treatment.

PMID- 25997617
TI  - MicroRNA-21 regulates intestinal epithelial tight junction permeability.
AB  - Increased tight junction (TJ) barrier permeability, induced by tumour necrosis
      factor (TNF)-alpha, may lead to the defects in TJ barrier and subsequent
      development of inflammation. Recent evidence suggests that miR-21 is implicated
      in inflammatory diseases. However, the physiological role of miR-21 in intestinal
      permeability remains elusive. This study aimed to explore the role of miR-21 in
      intestinal epithelial tight junction permeability. The filter-grown Caco-2
      monolayers model system was established to mimic intestinal barrier defect. The
      tight junction proteins were detected by immunofluorescence and western blot
      analysis. The expression of miR-21 was assessed by real-time polymerase chain
      reaction (PCR). We found that the expression of miR-21 was increased
      significantly in TNF-alpha induced intestinal TJ barrier defect model. miR-21
      overexpression significantly enhanced while miR-21 knockdown significantly
      decreased intestinal permeability. In addition, miR-21 overexpression
      significantly increased while miR-21 knockdown significantly decreased the levels
      of interleukin-6, interleukin-8 and prostaglandin E2 in cell culture medium.
      Furthermore, miR-21 positively regulated Akt phosphorylation and negatively
      regulated Phosphatase and tensin homolog (PTEN) expression in Caco-2 cells. Our
      results suggest that miR-21 may regulate intestinal epithelial tight junction
      permeability through PTEN/PI3K/Akt signalling pathway. This promotes the
      feasibility of targeting miR-21 in the clinical to preserve the intestinal
      barrier.

PMID- 25997618
TI  - The potential role of Alu Y in the development of resistance to SN38 (Irinotecan)
      or oxaliplatin in colorectal cancer.
AB  - BACKGROUND: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in
      the treatment of colorectal cancer. However, the frequent development of
      resistance to these drugs represents a considerable challenge in the clinic. Alus
      as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by
      carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or
      not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains
      unknown. RESULTS: We applied reduced representation bisulfite sequencing (RRBS)
      to investigate the DNA methylome in SN38 or oxaliplatin resistant colorectal
      cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue
      from 14 patients with colorectal cancer who either did or did not benefit from
      capecitabine + oxaliplatin treatment. For the clinical samples, we applied a
      concept of 'DNA methylation entropy' to estimate the diversity of DNA methylation
      states of the identified resistance phenotype-associated methylation loci
      observed in the cell line models. We identified different loci being
      characteristic for the different resistant cell lines. Interestingly, 53% of the
      identified loci were Alu sequences- especially the Alu Y subfamily. Furthermore,
      we identified an enrichment of Alu Y sequences that likely results from increased
      integration of new copies of Alu Y sequence in the drug-resistant cell lines. In
      the clinical samples, SOX1 and other SOX gene family members were shown to
      display variable DNA methylation states in their gene regions. The Alu Y
      sequences showed remarkable variation in DNA methylation states across the
      clinical samples. CONCLUSION: Our findings imply a crucial role of Alu Y in
      colorectal cancer drug resistance. Our study underscores the complexity of
      colorectal cancer aggravated by mobility of Alu elements and stresses the
      importance of personalized strategies, using a systematic and dynamic view, for
      effective cancer therapy.

PMID- 25997620
TI  - Maintaining the balance: both gain- and loss-of-function KCNA2 mutants cause
      epileptic encephalopathy.

PMID- 25997619
TI  - Anti-chondroitin sulfate proteoglycan 4-specific antibodies modify the effects of
      vemurafenib on melanoma cells differentially in normoxia and hypoxia.
AB  - Chondroitin sulfate proteoglycan 4 (CSPG4), a highly immunogenic melanoma tumor
      antigen, is a potential target for antibody-based immunotherapy. The mechanism by
      which CSPG4 affects melanoma progression is only partly understood, in particular
      the involvement of other receptor tyrosine kinases and the tumor
      microenvironment. We have previously reported on a mimotope-based vaccine against
      CSPG4 in a human melanoma xenograft model that resulted in reduction of tumor
      growth. Herein we describe the influence of hypoxia on the response to polyclonal
      anti-CSPG4-antibodies induced by this vaccine in combination with the BRAF
      inhibitor vemurafenib to enhance therapeutic efficacy by simultaneously targeting
      multiple signaling pathways. Melanoma cells were treated with polyclonal anti
      CSPG4-antibodies and vemurafenib. Proliferation, migration and invasion were
      evaluated in a real-time setting in the impedance-based x-CELLigence(r) system.
      Western blotting and quantitative PCR arrays were used to determine protein and
      mRNA expression of hypoxia inducible factor 1alpha (HIF1alpha), carbonic
      anhydrase IX (CAIX) and signaling pathway proteins. A melanoma xenograft model
      was used to detect HIF1alpha and CAIX expression in vivo. Hypoxia enhanced the
      antiproliferative response to vemurafenib. The migration and invasion capacities
      of vemurafenib-treated melanoma cells were increased, in spite of vemurafenib
      decreased expression of HIF1alpha and CAIX. Polyclonal anti-CSPG4-antibodies
      reduced the Transwell migration of vemurafenib-treated, BRAF V600E-mutant and
      CSPG4-expressing melanoma cells in hypoxia. This was associated with the
      downregulation of phosphorylated AKT, a kinase contributing to tumor cell
      migration. Our results highlight CSPG4 as a potential target for modulating
      treatment resistance to vemurafenib induced by the hypoxic microenvironment.

PMID- 25997621
TI  - In response to Letter to the Editor: beyond the randomised control--assessment
      tool.

PMID- 25997622
TI  - Retrospective Analysis of Vancomycin Nephrotoxicity in Elderly Chinese Patients.
AB  - This study explored nephrotoxicity in elderly Chinese patients after exposure to
      vancomycin and other nephrotoxic risk factors. This was a single-center
      retrospective study. The patient population included those who were >=60 years of
      age, had normal baseline serum creatinine values, and received vancomycin for
      >=48 h between January 1, 2013 and August 30, 2014. Nephrotoxicity occurred in
      29% of 124 patients. A baseline creatinine clearance >=63.5 ml/min was more
      common in the nephrotoxic group. Patients with high (>=15 mg/l) rather than low
      (<15 mg/l) average vancomycin troughs had elevated nephrotoxicity (47.2 vs.
      27.3%, p = 0.0001). Of the comorbid conditions evaluated, there were more
      patients with shock (p = 0.001), hypertension (p = 0.020) and congestive heart
      failure (p = 0.04) in the nephrotoxic group. Drugs frequently given at the same
      time with vancomycin, such as angiotensin receptor blockers and furosemide, were
      also associated with increased nephrotoxic risk. In conclusion, nephrotoxicity
      was frequently observed in patients with concurrent vancomycin trough
      concentrations >=15 MUg/ml and hypertension, shock, congestive heart failure. In
      addition, drugs concurrently used with vancomycin may also increase its
      nephrotoxicity. Therefore, renal function and vancomycin serum troughs should be
      closely monitored, especially in patients with other renal injury risk factors.

PMID- 25997623
TI  - Effects of dietary n-6/n-3 fatty acid ratio on nutrient digestibility and blood
      metabolites of Hanwoo heifers.
AB  - The objectives of this study were to investigate the effects of dietary n-6/n-3
      fatty acid (FA) ratio on digestibility, blood metabolites and FA profile of
      Hanwoo heifers. Fifteen Hanwoo heifers (22 +/- 3 months old; 357 +/- 69.7 kg)
      were randomly assigned to three dietary treatments with n-6/n-3 FA ratios of
      2.07, 5.18 and 7.37. The animals were housed individually in digestion crates and
      fed total mixed rations at 2.2% of body weight for 2 weeks of adaptation and 1
      week of collection. Treatment effects on in vivo digestibility, plasma metabolite
      and fatty acid profiles, and in vitro ruminal fermentation and fatty acid
      profiles were examined. In vivo digestibility was not affected (P > 0.05) by
      dietary n-6/n-3 FA ratio. However, in vitro dry matter digestibility and
      concentrations of total volatile fatty acids and propionate decreased (P < 0.05)
      linearly with increasing n-6/n-3 FA ratio. Plasma insulin and progesterone
      increased linearly (P < 0.05), but linolenic acid and total n-3 FA decreased
      linearly (P < 0.05) with increasing n-6/n-3 ratio. Increasing the dietary n-6/n-3
      FA ratio can increase the n-6/n-3 FA ratio in plasma and ruminal fluid as well as
      plasma progesterone secretion. 

PMID- 25997624
TI  - Sixth cranial nerve palsy due to acitretin.

PMID- 25997625
TI  - Identify Potential Regulators in HIV-1 Latency by Joint microRNA and mRNA
      Analysis.
AB  - BACKGROUND/AIMS: The main obstacle to cure HIV infection is the existence of long
      lasting latent reservoirs. Many efforts have been made to understand basal
      mechanisms of HIV-1 latency, in which miRNAs play an important role. However,
      integrated analysis of miRNA and mRNA expression in HIV-1 latency is lacking.
      METHODS AND RESULTS: Global miRNA and mRNA expression was determined by
      microarrays and quantitative reverse transcription PCR in well-characterized HIV
      1 latently and actively infected cells, respectively. Interactions of miRNA-mRNA,
      mRNA-mRNA, and transcription factor-miRNA pairs were assembled into the function
      network. Our results show that transcription regulation related genes were mostly
      enriched in HIV-1 latently infected cells. Gene set enrichment analysis revealed
      nuclear transport related pathways were up-regulated in the latency group.
      Network dynamic analysis highlighted many gene-pairs sharing the largest changes
      in different HIV-1 infection state. 83.33% miRNA-target pairs were validated
      against database, and RHOB related genes constitute the interface between HIV-1
      latency and replication state. CONCLUSION: We show for the first time a joint
      miRNA and mRNA expression profile related to a HIV-1 latency phenotype, outline a
      dynamic network of potential regulators involving in HIV-1 latency or replication
      state, and gain new insights into the source messages for affecting HIV-1
      latency.

PMID- 25997627
TI  - Program summary.

PMID- 25997626
TI  - Type II (adult onset) Alexander disease in a paraplegic male with a rare D128N
      mutation in the GFAP gene.

PMID- 25997630
TI  - Poster presentations.

PMID- 25997631
TI  - Impact of UKPDS risk estimation added to a first subjective risk estimation on
      management of coronary disease risk in type 2 diabetes - An observational study.
AB  - AIMS: To investigate the impact of the UKPDS risk engine on management of CHD
      risk in T2DM patients. METHODS: Observational study among 139 GPs. Data from 933
      consecutive patients treated with a maximum of two oral glucose lowering drugs,
      collected at baseline and after twelve months. GPs estimated the CHD risk
      themselves and afterwards they calculated this with the UKPDS risk engine. Under-
      and overestimation were defined as a difference >5 percentage points difference
      between both calculations. The impact of the UKPDS risk engine was assessed by
      measuring differences in medication adjustments between the over-, under- and
      accurately estimated group. RESULTS: In 42.0% the GP accurately estimated the CHD
      risk, in 32.4% the risk was underestimated and in 25.6% overestimated. Mean
      difference between the estimated (18.7%) and calculated (19.1%) 10 years CHD risk
      was -0.36% (95% CI -1.24 to 0.52). Male gender, current smoking and total
      cholesterol level were associated with underestimation. Patients with an
      subjectively underestimated CHD risk received significantly more medication
      adjustments. Their UKPDS 10 year CHD risk did not increase during the follow-up
      period, contrary to the other two groups of patients. CONCLUSIONS: The UKPDS risk
      engine may be of added value for risk management in T2DM.

PMID- 25997632
TI  - Associations of marital violence with different forms of contraception: cross
      sectional findings from South Asia.
AB  - OBJECTIVE: To assess associations between marital violence and type of
      contraception among women in South Asia. METHODS: Cross-sectional analyses were
      conducted using marital violence data collected during the most recent
      Demographic and Health Surveys from Bangladesh (n=3665), India (n=56357), and
      Nepal (n=3037). Data were pooled to assess associations of marital violence
      (physical or sexual) with modern contraception use (current spacing or
      sterilization). RESULTS: Sexual marital violence was associated with both modern
      spacing contraception (adjusted odds ratio [AOR] 1.30; 95% confidence interval
      [CI], 1.13-1.49) and sterilization (AOR 0.79; 95% CI, 0.70-0.88). Sexual violence
      was reported more often by pill users (9.8% vs 5.5% for non-users) but less often
      by condom users (4.5% vs 5.8% for non-users). CONCLUSION: Sexual marital violence
      might increase use of contraception that need not require husband involvement
      (pill) but decrease use of methods that require his cooperation (condom) or
      support for mobility, funds, or time (sterilization).

PMID- 25997633
TI  - MEDUCATE trial: effectiveness of an intensive EDUCATional intervention for IT
      mediated MEDication management in the outpatient clinic - study protocol for a
      cluster randomized controlled trial.
AB  - BACKGROUND: Using information technology for medication management is an
      opportunity to help physicians to improve the quality of their documentation and
      communication and ultimately to improve patient care and patient safety.
      Physician education is necessary to take full advantage of information technology
      systems. In this trial, we seek to determine the effectiveness of an intensive
      educational intervention compared with the standard approach in improving
      information technology-mediated medication management and in reducing potential
      adverse drug events in the outpatient clinic. METHODS/DESIGN: We are conducting a
      multicenter, cluster randomized controlled trial. The participants are
      specialists and residents working in the outpatient clinic of internal medicine,
      cardiology, pulmonology, geriatrics, gastroenterology and rheumatology. The
      intensive educational intervention is composed of a small-group session and e
      learning. The primary outcome is discrepancies between registered medication (by
      physicians) and actually used medication (by patients). The key secondary
      outcomes are potential adverse events caused by missed drug-drug interactions.
      The primary and key secondary endpoints are being assessed shortly after the
      educational intervention is completed. Sample size will be calculated to ensure
      sufficient power. A sample size of 40 physicians per group and 20 patients per
      physician will ensure a power of >90 %, which means we will need a total of 80
      physicians and 1,600 patients. DISCUSSION: We performed an exploratory trial
      wherein we tested the recruitment process, e-learning, time schedule, and methods
      for data collection, data management and data analysis. Accordingly, we refined
      the processes and content: the recruitment strategy was intensified, extra
      measures were taken to facilitate smooth conductance of the e-learning and parts
      were made optional. First versions of the procedures for data collection were
      determined. Data entry and analysis was further standardized by using the G
      standard database in the telephone questionnaire. TRIAL REGISTRATION: ISRCTN
      registry: ISRCTN50890124 . Registered 10 June 2013.

PMID- 25997634
TI  - Antinociceptive and anti-tussive activities of the ethanol extract of the flowers
      of Meconopsis punicea Maxim.
AB  - BACKGROUND: As an important traditional Tibetan (veterinary) medicine, the
      flowers of Meconopsis punicea (family Papaveraceae) have been used to treat pain,
      fever, cough, inflammation, liver heat and lung heat of humans and animals by
      local people for thousands of years. In this paper, we aimed to investigate the
      antinociceptive and anti-tussive activities of the ethanol extract of M. punicea
      (EEM). METHODS: Firstly, HPLC was used to analyze the main constituents of the
      ethanol extract of M. punicea. In animal experiments, the acetic acid-induced
      writhing response test, hot plate test, barbiturate-induced sleeping time and
      formalin tests were used to evaluate the antinociceptive activity. Then, ammonia
      induced coughing and sulfur dioxide-induced coughing tests in mice as well as the
      phenol red secretion in trachea test were used to investigate the anti-tussive
      activity of the extract. Finally, an acute toxicity study was carried out.
      RESULTS: The results showed that alkaloids and flavonoids were the main compounds
      in the ethanol extract of M. punicea flowers. The extract at 125, 250 and 500
      mg/kg had good antinociceptive and anti-tussive activities in mice with a dose
      dependent manner. CONCLUSIONS: These findings suggested that EEM has significant
      bioactivities, and the active components of M. punicea should be studied further.

PMID- 25997635
TI  - The relationship between bond ionicity, lattice energy, coefficient of thermal
      expansion and microwave dielectric properties of Nd(Nb(1-x)Sb(x))O4 ceramics.
AB  - The crystalline structure refinement, chemical bond ionicity, lattice energy and
      coefficient of thermal expansion were carried out for Nd(Nb(1-x)Sb(x))O4 ceramics
      with a monoclinic fergusonite structure to investigate the correlations between
      the crystalline structure, phase stability, bond ionicity, lattice energy,
      coefficient of thermal expansion, and microwave dielectric properties. The bond
      ionicity, lattice energy, and coefficient of thermal expansion of Nd(Nb(1
      x)Sb(x))O4 ceramics were calculated using a semiempirical method based on the
      complex bond theory. The phase structure stability varied with the lattice energy
      which was resulted by the substitution constant of Sb(5+). With the increasing of
      the Sb(5+) contents, the decrease of Nb/Sb-O bond ionicity was observed, which
      could be contributed to the electric polarization. The epsilon(r) had a close
      relationship with the Nb/Sb-O bond ionicity. The increase of the Q*f and |tau(f)|
      values could be attributed to the lattice energy and the coefficient of thermal
      expansion. The microwave dielectric properties of Nd(Nb(1-x)Sb(x))O4 ceramics
      with the monoclinic fergusonite structure were strongly dependent on the chemical
      bond ionicity, lattice energy and coefficient of thermal expansion.

PMID- 25997636
TI  - Characteristics of Neuro-Behcet's Disease in a Case-Series from a Single Centre
      in Northern Portugal.
AB  - INTRODUCTION: Behcet's disease (BD) is a multisystem inflammatory disease of
      unknown etiology that may affect the CNS - Neuro-Behcet (NB). Our aim was to
      evaluate the frequency of neurological involvement and characterize a cohort of
      our NB patients. METHODS: We retrospectively revised the clinical, laboratory and
      imaging data of a cohort of BD patients, followed in our hospital outpatient
      clinic. RESULTS: We identified 138 BD patients. Twenty-five out of 138 had NB (15
      female). Four patients presented with neurological symptoms. We identified a
      total of 37 attacks. Twenty-one attacks were classified as parenchymatous, four
      non-parenchymatous and 12 as other syndromes. Seventeen patients had CSF analysis
      performed (20 samples). Five samples were normal, 15 showed CSF pleocytosis. The
      most frequent finding on MRI performed in the acute phase was extensive lesions
      involving the brainstem. Two patients died due to the neurological involvement of
      BD. CONCLUSION: We found 18.1% prevalence of NB and a higher female-to-male ratio
      in our group than in other series. Gastrointestinal and vascular involvement was
      more frequent in the NB group. The fact that neurological involvement may be the
      first manifestation of BD with therapeutic implications and associated morbidity
      points out the relevance of an early diagnosis.

PMID- 25997638
TI  - Shared decision-making in epilepsy management--Its time has come, but are we
      missing some concepts?

PMID- 25997637
TI  - Forehead EEG electrode set versus full-head scalp EEG in 100 patients with
      altered mental state.
AB  - BACKGROUND: Acute EEG is vastly underutilized in acute neurological settings. The
      most common reason for this is simply the fact that acute EEG is not available
      when needed or getting EEG is delayed as it requires trained technicians and
      equipment to be properly recorded. We have recently described a handy disposable
      forehead EEG electrode set that is suitable for acute emergency EEG recordings.
      The specific objective in this study was to assess the forehead electrode's
      utility when the clinical demand was to exclude SE. PATIENTS AND METHODS: One
      hundred consecutive acute neurological patients (53 women, 47 men, age: 18-90
      years) with unexplained altered mental state were studied with acute emergency
      EEG to rule out SE. Electroencephalographic recordings were obtained
      simultaneously with forehead EEG electrode and routine 10-20 system full-head
      scalp electrodes to clarify the clinical usefulness of forehead EEG electrode in
      this setting. Electroencephalographic recordings were interpreted blindly by
      three experienced clinical neurophysiologists first only based on forehead EEG
      and then by full-head EEG. RESULTS: Ninety-six out of the 100 patients did not
      show EEG evidence of SE. There was 100% agreement with forehead and routine EEG.
      Four out of the 100 patients showed EEG evidence of SE in routine EEG, with 50%
      agreement between different electrode types. The forehead EEG missed two cases
      because the EEG findings supporting SE were restricted to the posterior parts of
      the brain. MAJOR CONCLUSIONS: With a forehead EEG set, the sensitivity of
      detecting NCSE was 50%. There were no false positive cases yielding a specificity
      of 100%. Patients with AMS can benefit from forehead EEG recording in
      prehospital, hospital, and ICU settings. Since EEG recording can be started
      within a few minutes with the forehead EEG set, it will significantly reduce the
      delay in treatment of SE. This article is part of a Special Issue entitled
      "Status Epilepticus".

PMID- 25997639
TI  - Parents of Children With Cancer: At-Risk or Resilient?
AB  - OBJECTIVE: To examine adjustment in parents of children with cancer using a
      design that minimizes focusing effects and allows for direct comparison with
      parents of healthy children. METHOD: Parents of 305 children with cancer and a
      demographically similar sample of 231 parents of healthy children were evaluated
      using diagnostic interviews for posttraumatic stress disorder (PTSD), and
      questionnaire measures of posttraumatic stress symptoms (PTSS) and psychological
      growth (PG), as well as measures of global psychological functioning. RESULTS:
      Rates of current and lifetime PTSD in parents of children with cancer were low,
      and did not differ from comparison parents. Likewise, levels of PTSS were not
      significantly different from comparison parents, but differed as a function of
      time since diagnosis, with parents of children who were >= 5 years from diagnosis
      reporting significantly lower PTSS than comparison parents. PG was higher in
      parents of children with cancer than in comparison parents regardless of time
      since diagnosis. CONCLUSION: Parents of children with cancer demonstrate
      resilience to this challenge.

PMID- 25997641
TI  - End of the gold rush for China's drugs market?

PMID- 25997640
TI  - A variable number of tandem repeats in the 3'-untranslated region of the dopamine
      transporter modulates striatal function during working memory updating across the
      adult age span.
AB  - Dopamine modulation of striatal function is critical for executive functions such
      as working memory (WM) updating. The dopamine transporter (DAT) regulates
      striatal dopamine signaling via synaptic reuptake. A variable number of tandem
      repeats in the 3'-untranslated region of SLC6A3 (DAT1-3'-UTR-VNTR) is associated
      with DAT expression, such that 9-repeat allele carriers tend to express lower
      levels (associated with higher extracellular dopamine concentrations) than 10
      repeat homozygotes. Aging is also associated with decline of the dopamine system.
      The goal of the present study was to investigate the effects of aging and DAT1-3'
      UTR-VNTR on the neural activity and functional connectivity of the striatum
      during WM updating. Our results showed both an age-related decrease in striatal
      activity and an effect of DAT1-3'-UTR-VNTR. Ten-repeat homozygotes showed reduced
      striatal activity and increased striatal-hippocampal connectivity during WM
      updating relative to the 9-repeat carriers. There was no age by DAT1-3'-UTR-VNTR
      interaction. These results suggest that, whereas striatal function during WM
      updating is modulated by both age and genetically determined DAT levels, the rate
      of the age-related decline in striatal function is similar across both DAT1-3'
      UTR-VNTR genotype groups. They further suggest that, because of the baseline
      difference in striatal function based on DAT1-3'-UTR-VNTR polymorphism, 10-repeat
      homozygotes, who have lower levels of striatal function throughout the adult life
      span, may reach a threshold of decreased striatal function and manifest
      impairments in cognitive processes mediated by the striatum earlier in life than
      the 9-repeat carriers. Our data suggest that age and DAT1-3'-UTR-VNTR
      polymorphism independently modulate striatal function. 

PMID- 25997642
TI  - Angiotensin-converting enzyme genotype is not a significant genetic risk factor
      for idiopathic nephrotic syndrome in Croatian children.
AB  - AIM: The association of the angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism with idiopathic nephrotic syndrome (INS) is
      controversial. Only scarce information on European populations is available. The
      aim of the study was to investigate the distribution of the ACE gene I/D
      polymorphism and its impact on INS in children from Croatia. MATERIALS AND
      METHODS: Ninety-five children with INS were investigated: 30 with minimal change
      disease (MCD), 35 with mesangial proliferative glomerulonephritis (MesPGN) and 30
      with focal segmental glomerulosclerosis (FSGS). The control group consisted of 73
      healthy adults. ACE gene was analyzed using the PCR method. The results were
      correlated with clinical features, renal morphology and response to
      immunosuppresive therapy. RESULTS: There was no correlation of ACE genotype with
      gender, age of the disease onset, level of proteinuria, presence of hematuria or
      hypertension, and GFR at onset of the disease. No statistically significant
      differences in ACE genotype or allele frequencies between the controls and whole
      group of patients, MCD group, MesPGN group, FSGS group, steroid sensitive (SS)
      patients, steroid resistant (SR) patients, as well as each other, were found,
      although DD genotype tended to be more frequent in FSGS patients, SR patients,
      and frequent relapsers. Among 11 children treated with cyclophosphamide the D
      allele was significantly higher among non-responders (p = 0.003). CONCLUSION: DD
      genotype is not a genetic risk factor for acquiring INS nor significant phenotype
      modifier regarding to clinical and pathohistological picture and response to
      steroids in Croatian children. The potential application of ACE genotyping in
      predicting cyclophosphamide response deserves further investigation.

PMID- 25997643
TI  - Effectiveness of mobile technologies delivering Ecological Momentary
      Interventions for stress and anxiety: a systematic review.
AB  - OBJECTIVES: Mobile technologies may be suitable for delivering Ecological
      Momentary Interventions (EMI) to treat anxiety in real-time. This review aims to
      synthesize evidence on the effectiveness of EMI for treating anxiety conditions.
      MATERIALS AND METHODS: Four databases and the reference lists of previous studies
      were searched. A total of 1949 abstracts were double screened for inclusion.
      Sufficient studies were available to undertake a quantitative meta-analysis on
      EMIs on generalized anxiety symptoms. RESULTS: The 15 randomized trials and
      randomized controlled trials examined anxiety (n = 7), stress (n = 3), anxiety
      and stress (n = 2), panic disorder (n = 2), and social phobia (n = 1). Eight EMIs
      comprised self-monitoring integrated with therapy modules, seven comprised
      multimedia content, and three comprised self-monitoring only. The quality of
      studies presented high risk of biases. Meta-analysis (n = 7) demonstrated that
      EMIs reduced generalized anxiety compared to control and/or comparison groups
      (Effect Size (ES) = 0.32, 95% CI, 0.12-0.53). Most EMIs targeting stress were
      reported effective relative to control as were the two EMIs targeting panic
      disorders. The EMI targeting social phobia was not effective. DISCUSSION: EMIs
      have potential in treating both anxiety and stress. However, few high-quality
      trials have been conducted for specific anxiety disorders. Further trials are
      needed to assess the value of EMI technologies for anxiety in enhancing existing
      treatments. CONCLUSION: This study found a small significant effect of EMI
      studies on reducing generalized anxiety. Studies on stress demonstrated EMI was
      effective compared to control, with the small number of studies on panic and
      social phobia demonstrating mixed results.

PMID- 25997644
TI  - Higher, faster, worse? An event-related potentials study of affective picture
      processing in migraine.
AB  - BACKGROUND: Migraine is a disorder of periodic disabling headache. Facilitated
      cortical responsivity has been suggested as one predisposing factor. Although the
      underlying mechanisms of migraine attack onsets are not fully understood,
      facilitated cortical responsivity has been suggested as one predisposing factor.
      Here, we investigate if enhanced cortical responsivity is reflected in altered
      event-related potentials during processing of complex pictures. METHOD:
      Altogether, 16 migraine patients and 16 healthy volunteers participated in this
      study. Each patient had a diagnosed migraine and was headache- and medication
      free for the study. Participants watched positive, negative and neutral pictures
      from the international affective picture system. An electroencephalogram was
      recorded during picture presentation. Afterwards, participants were asked to rate
      the pictures for valence and arousal. RESULTS: Migraine patients showed
      significantly more negative-going early event-related potential components from
      100 ms to 180 ms to all picture categories over occipital regions as well as more
      positive-going late potentials over central regions. Patients and controls did
      not differ in valence and arousal ratings for the international-affective picture
      system. DISCUSSION: Patients with migraine seem to react cortically more
      intensely to all kinds of pictorial stimuli, regardless of emotional content.
      This facilitated processing may be related to the high cortical responsivity
      shown in various other event-related potential studies and might contribute to
      the recurring intense headache attacks.

PMID- 25997645
TI  - Vaccination of lambs with the recombinant protein rHc23 elicits significant
      protection against Haemonchus contortus challenge.
AB  - Gene encoding a somatic protein of Haemonchus contortus (Hc23) known to confer
      significant protection against experimental haemonchosis has been cloned and
      expressed in a prokaryotic system. A cDNA library of H. contortus using the
      vector lambda ZAP II was obtained. Full-length gene was amplified, cloned and
      expressed in Escherichia coli BL21. The recombinant protein was purified in Ni
      NTA column. Recombinant protein (rHc23) had 203 aminoacids and a molecular mass
      of 24.15 kDa. Recombinant protein (100 MUg/dose) with aluminum hydroxide as
      adjuvant was administered to 5-6 months age female Assaf lambs on days -42, -28
      and -14. On day 0 animals were infected with 15,000 L3 of H. contortus.
      Vaccination with rHc23 elicited a significant protection against challenge, with
      >80% reductions in both fecal egg counts and average abomasal parasite burdens at
      the end of the experiment (45 days post challenge) besides lack of variations in
      packed cell volume. Results support the feasibility of vaccination against lamb
      haemonchosis with a recombinant product from an exposed antigen.

PMID- 25997646
TI  - Proteomic analysis of differentially expressed proteins in the marine fish
      parasitic ciliate Cryptocaryon irritans.
AB  - Cryptocaryoniasis is a severe disease of farmed marine fish caused by the
      parasitic ciliate Cryptocaryon irritans. This disease can lead to considerable
      economic loss, but studies on proteins linked to disease development and
      antigenic proteins for vaccine development have been relatively scarce to date.
      In this study, 53 protein spots with differential abundance, representing 12
      proteins, were identified based on a pair-wise comparison among theronts,
      trophonts, and tomonts. Meanwhile, 33 protein spots that elicited serological
      responses in rabbits were identified, representing 9 proteins. In addition, 27
      common antigenic protein spots reacted with grouper anti-sera, representing 10
      proteins. Most of the identified proteins were involved in cytoskeletal and
      metabolic pathways. Among these proteins, actin and alpha-tubulin appeared in all
      three developmental stages with differences in molecular weights and isoelectric
      points; 4 proteins (vacuolar ATP synthase catalytic subunit alpha, mcm2-3-5
      family protein, 26S proteasome subunit P45 family protein and dnaK protein) were
      highly expressed only in theronts; while protein kinase domain containing protein
      and heat shock protein 70 showed high levels of expression only in trophonts and
      tomonts, respectively. Moreover, actin was co-detected with 3 rabbit anti-sera
      while beta-tubulin, V-type ATPase alpha subunit family protein, heat shock
      protein 70, mitochondrial-type hsp70, and dnaK proteins showed immunoreactivity
      with corresponding rabbit anti-sera in theronts, trophonts, and tomonts.
      Furthermore, beta-tubulin, the metabolic-related protein enolase, NADH-ubiquinone
      oxidoreductase 75 kDa subunit, malate dehydrogenase, as well as polypyrimidine
      tract-binding protein, glutamine synthetase, protein kinase domain containing
      protein, TNFR/NGFR cysteine-rich region family protein, and vacuolar ATP synthase
      catalytic subunit alpha, were commonly detected by grouper anti-sera. Therefore,
      these findings could contribute to an understanding of the differences in gene
      expression and phenotypes among the different stages of parasitic infection, and
      might be considered as a source of candidate proteins for disease diagnosis and
      vaccine development.

PMID- 25997647
TI  - Onset of efficacy and residual speed of kill over one month of a topical
      dinotefuran-permethrin-pyriproxyfen combination (Vectra (r) 3D) against the adult
      cat flea (Ctenocephalides felis felis) on dogs.
AB  - This study was designed to assess the onset of therapeutic and residual
      insecticidal efficacy of a topical ectoparasiticide (Vectra((r))3D, DPP) on dogs
      over one month against the cat flea, Ctenocephalides felis felis. Adult dogs
      (n=32, 11.0-18.7 kg) were infested with 100 adult fleas on days -6, -2, 7, 14, 21
      and 28. Based on flea retention, the dogs were allocated in two groups and were
      treated topically on day 0 with a control solution (CS) or DPP. Each group was
      divided in two subgroups in which live fleas were counted by combing the dogs 2
      or 6h after treatment and at each re-infestation. The insecticidal efficacy was
      calculated using arithmetic and geometric means at each time point. The flea
      retention rate ranged from 64.0 to 86.5% in the CS group throughout the study.
      Based on arithmetic means, the therapeutic efficacy was 96.4% 6h post-treatment
      and residual efficacies ranged from 96.8 to 99.9% 2h after each re-infestation.
      The residual speed of killing effectiveness, >96% at 2h, persisted for one month
      after treatment. DPP administration was well tolerated. This study confirms that
      DPP starts killing fleas within 2h after treatment and reaches efficacy levels
      >95% at 6h. We have shown that DPP kills >96.8% of fleas for one month after
      treatment within 2h after infestation.

PMID- 25997648
TI  - Synthesis of enantioenriched 1,2-trans-diamines using the borono-Mannich reaction
      with N-protected alpha-amino aldehydes.
AB  - The three-component Petasis borono-Mannich reaction starting with easily
      accessible N-protected alpha-amino aldehydes produces efficiently and
      diastereoselectively 1,2-trans-diamines with an enantiomeric excess of up to 98%.

PMID- 25997649
TI  - The AAMD: Its History and Future. Introduction.

PMID- 25997650
TI  - Polymer/Nanoparticle Hybrid Materials of Precise Dimensions by Size-Exclusive
      Fishing of Metal Nanoparticles.
AB  - Polymer cages prepared by etching of gold nanoparticles from polymer templates by
      the "grafting around" method are designed for selective separation of metal
      nanoparticles. The separation process is demonstrated as a fast biphasic ligand
      exchange reaction. The high separation efficiency and size selectivity of the
      polymer cage is verified by comparison with the linear block copolymer. 

PMID- 25997651
TI  - Biocuration at the Saccharomyces genome database.
AB  - Saccharomyces Genome Database is an online resource dedicated to managing
      information about the biology and genetics of the model organism, yeast
      (Saccharomyces cerevisiae). This information is derived primarily from scientific
      publications through a process of human curation that involves manual extraction
      of data and their organization into a comprehensive system of knowledge. This
      system provides a foundation for further analysis of experimental data coming
      from research on yeast as well as other organisms. In this review we will
      demonstrate how biocuration and biocurators add a key component, the biological
      context, to our understanding of how genes, proteins, genomes and cells function
      and interact. We will explain the role biocurators play in sifting through the
      wealth of biological data to incorporate and connect key information. We will
      also discuss the many ways we assist researchers with their various research
      needs. We hope to convince the reader that manual curation is vital in converting
      the flood of data into organized and interconnected knowledge, and that
      biocurators play an essential role in the integration of scientific information
      into a coherent model of the cell.

PMID- 25997652
TI  - Sclerostin quo vadis? - is this a useful long-term mortality parameter in
      prevalent hemodialysis patients?
AB  - BACKGROUND/AIMS: Cardiovascular calcification contributes to the increased
      mortality in hemodialysis patients. Sclerostin was identified as an antianabolic
      bone factor causing soft tissue calcification. Data on prospective large-scale
      studies associating sclerostin with mortality in hemodialysis patients are so far
      inconsistent. METHODS: In our multicenter prospective longitudinal study
      following hemodialysis patients, we assessed the associations of sclerostin and
      bone remodeling markers with long-term mortality. We evaluated the relationship
      between circulating sclerostin, Fibroblast growth factor 23 (FGF23) and
      traditional bone remodeling markers. Sclerostin levels in hemodialysis patients
      were compared with healthy controls. RESULTS: We enrolled 239 hemodialysis
      patients with a median follow up of 1461 days. In Cox regression analysis, FGF23
      (HR 1.40;95%CI 1.11-1.76), parathyroid hormone (PTH) (HR 1.80;95%CI 1.44-2.26)
      and alkaline phosphatase (AP) (HR 1.50;95%CI 1.10-2.04) per SD, 25(OH)vitamin D
      (HR 0.42;95%CI 0.23-0.76) per natural log but not sclerostin (HR 1.02;95%CI 0.75
      1.38) per SD increase were associated with mortality. FGF23, PTH and AP were
      negatively associated with sclerostin. Among control and hemodialysis females,
      sclerostin levels were lower than in men. CONCLUSION: Higher FGF23, PTH, AP and
      lower 25(OH)vitamin D but not sclerostin predict long-term mortality. Sclerostin
      was negatively associated with FGF23, PTH and AP and lower in females than in
      males.

PMID- 25997653
TI  - A dose response randomised controlled trial of docosahexaenoic acid (DHA) in
      preterm infants.
AB  - Thirty one infants born less than 30 weeks' gestational age were randomised to
      receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic
      acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4
      days of the first enteral feed. Twenty three infants were enroled in non
      randomised reference groups; n=11 who had no supplementary DHA and n=12 who had
      maternal DHA supplementation. All levels of DHA in the emulsion were well
      tolerated with no effect on number of days of interrupted feeds or days to full
      enteral feeds. DHA levels in diets were directly related to blood DHA levels but
      were unrelated to arachidonic acid (AA) levels. All randomised groups and the
      maternal supplementation reference group prevented the drop in DHA levels at
      study end that was evident in infants not receiving supplementation. Australian
      New Zealand Clinical Trials Registry: ACTRN12610000382077. 

PMID- 25997654
TI  - Linking Exposures of Particles Released From Nano-Enabled Products to Toxicology:
      An Integrated Methodology for Particle Sampling, Extraction, Dispersion, and
      Dosing.
AB  - Nano-enabled products (NEPs) represent a growing economic global market that
      integrates nanotechnology into our everyday lives. Increased consumer use and
      disposal of NEPs at their end of life has led to increased environmental, health
      and safety (EHS) concerns, due to the potential environmental release of
      constituent engineered nanomaterials (ENMs) used in the production of NEPs.
      Although, there is an urgent need to assess particulate matter (PM) release
      scenarios and potential EHS implications, no current standardized methodologies
      exist across the exposure-toxicological characterization continuum. Here, an
      integrated methodology is presented, that can be used to sample, extract,
      disperse and estimate relevant dose of life cycle-released PM (LCPM), for in
      vitro and in vivo toxicological studies. The proposed methodology was utilized to
      evaluate two "real world" LCPM systems simulating consumer use and disposal of
      NEPs. This multi-step integrated methodology consists of: (1) real-time
      monitoring and sampling of size fractionated LCPM; (2) efficient extraction of
      LCPM collected on substrates using aqueous or ethanol extraction protocols to
      ensure minimal physicochemical alterations; (3) optimized LCPM dispersion
      preparation and characterization; (4) use of dosimetric techniques for in vitro
      and in vivo toxicological studies. This comprehensive framework provides a
      standardized protocol to assess the release and toxicological implications of
      ENMs released across the life cycle of NEPs and will help in addressing important
      knowledge gaps in the field of nanotoxicology. 

PMID- 25997655
TI  - Interactive Effects of N6AMT1 and As3MT in Arsenic Biomethylation.
AB  - In humans, arsenic is primarily metabolized by arsenic (+3 oxidation state)
      methyltransferase (As3MT) to yield both trivalent and pentavalent methylated
      metabolites. We recently reported that the putative N-6 adenine-specific DNA
      methyltransferase 1 (N6AMT1) can biotransform monomethylarsonous acid (MMA(III))
      to dimethylarsinic acid, conferring resistance of human cells to arsenic
      exposure. To further decipher the role of N6AMT1 and its interaction with As3MT
      in arsenic biomethylation, we examined the relative contribution of N6AMT1 and
      As3MT in metabolizing arsenic using several newly modified UROtsa human
      urothelial cells, ie, UROtsa cells with either a constant level of N6AMT1 or
      As3MT in combination with an inducible level of As3MT or N6AMT1, respectively.
      Our analysis confirmed the involvement of N6AMT1 in MMA(III) biomethylation but
      not for inorganic arsenic. In a comparable level of N6AMT1 and As3MT, the effect
      of N6AMT1 mediated MMA(III) biomethylation was obscured by the action of As3MT.
      Furthermore, we showed that the levels of N6AMT1 and As3MT proteins varied among
      and within human normal and cancerous tissues. Overall, the data showed that
      N6AMT1 has a role in MMA(III) biomethylation, but its effect is relatively minor
      and limited compared with As3MT. In addition, the varied levels and distributions
      of N6AMT1 and As3MT among human tissues may potentially contribute to the tissue
      specificity and susceptibility to arsenic toxicity and carcinogenicity. 

PMID- 25997656
TI  - Ruthenium-catalyzed decarbonylative addition reaction of anhydrides with alkynes:
      a facile synthesis of isocoumarins and alpha-pyrones.
AB  - A novel ruthenium catalyzed straightforward and efficient synthesis of
      isocoumarin and alpha-pyrone derivatives has been accomplished by the
      decarbonylative addition reaction of anhydrides with alkynes under thermal
      conditions. 

PMID- 25997657
TI  - Evaluation of tuberculosis public health surveillance, Al-Madinah province,
      Kingdom of Saudi Arabia, 2012.
AB  - The objective of the study is to evaluate the quality of the data, the
      sensitivity of the surveillance, and the completeness of identification and
      investigation of tuberculosis (TB) patient's contacts. The study covered the TB
      surveillance program in Al-Madinah province in 2011. First, we reviewed all the
      notifications, treatment cards, and register books, as well as monthly and
      quarterly reports, for completeness and accuracy of data. Then, we searched for
      the missed cases that were not reported. Finally, we reviewed all the patients'
      household contacts' reports to assess the degree of completion of identification
      and investigation. There were 444 cases detected during the study period; only
      200 cases were reported. The sensitivity of the TB surveillance system was 45%.
      Among the 200 reported cases, the results revealed high completeness rates for
      demographic and disease data and low completeness rates for the test result
      fields. The contact identification and investigation showed that 34.4% of smear
      positive cases' contacts were not identified. Only 67% of identified contacts
      were investigated. The review of hospital records and lab registers showed that
      244 cases were not reported. In conclusion, the TB surveillance system has
      several areas that need improvement. 

PMID- 25997658
TI  - Pityriasis Rosea in Children: Clinical Features and Laboratory Investigations.
AB  - Pityriasis rosea (PR) is a common, self-limiting exanthematous disease associated
      with a systemic reactivation of human herpesvirus 6 (HHV-6) and/or HHV-7. It
      usually occurs in the second or third decade of life whereas it is uncommon in
      patients younger than 10 years. We studied the clinical features and virological
      parameters of 31 children with PR, comparing them with those in adults. Our
      findings indicate that PR presents different characteristics between children and
      adults, mainly consisting of time lapse between herald patch and generalized
      eruption, duration of the exanthem, oropharyngeal involvement and persistence of
      HHV-6 and HHV-7 plasma viremia. Overall, these results suggest that, following
      HHV-6 and/or HHV-7 systemic active infection, the pathogenetic mechanisms
      involved in PR may at least partly be different in children and adults.

PMID- 25997659
TI  - Design of the interface of edible nanoemulsions to modulate the bioaccessibility
      of neuroprotective antioxidants.
AB  - Most frequently the use of bioactive molecules for the supplementation of food
      and beverages is hampered by stability limitations or inadequate intestinal
      absorption. This work evaluates in vitro the role that the interface of the
      nanoemulsion has on the physicochemical properties, the stability behavior and
      the enzymatic degradation after oral intake. For that purpose three soybean oil
      (SB) formulations were studied. These formulations were based on the emulsifier
      lecithin but modified with two non-ionic surfactants Pluronic((r)) F68 (PF68) or
      Pluronic((r)) F127 (PF127) yielding (i) SB-NE (only lecithin on the interface),
      (ii) SB-NE PF68 (lecithin plus PF68) and 9 (iii) SB-NE PF127 (lecithin plus
      PF127). All the formulations tested were low polydispersed and showed a size of
      about 200 nm and zeta-potential of -50 mV. The in vitro colloidal stability assay
      showed that lecithin itself was able to promote that formulations reach unaltered
      to the small intestine and facilitate the absorption of the antioxidant payload
      on a tunable fashion there (with in vitro bioaccessibility values from around 40%
      up to a 70%). PF68 was able to sterically stabilize the formulation against the
      aggregation induced by the pH and electrolytes of the simulated gastrointestinal
      track; however, this surfactant was easily displaced by the lipases of the
      simulated intestinal milieu being unable to modulate the digestion pattern of the
      oil droplets in the small intestine. Finally, PF127 displayed a strong steric
      potential that dramatically reduced the interaction of the oil droplets with
      lipases in vitro, which will compromise the capacity of the formulation to
      improve the bioaccessibility of the loaded antioxidant.

PMID- 25997661
TI  - Spectroscopic and calorimetric studies of formation of the supramolecular
      complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous
      solution.
AB  - The results of spectroscopic measurements (increase in solubility, equilibrium
      dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration
      ITC) indicate exothermic (DeltaH<0) and spontaneous (DeltaG < 0) combination of
      an antitumor drug, 5-fluorouracil, by both cationic PAMAM G5-NH2 dendrimer and
      its hydroxyl analog PAMAM G5-OH in aqueous solutions at room temperature. PAMAM
      G5-NH2 dendrimer combines about 70 molecules of the drug with equilibrium
      constant K ? 300, which is accompanied by an increase in the system order (DeltaS
      < 0). Hydroxyl dendrimer, PAMAM G5-OH, combines about 14 molecules of 5
      fluorouracil with equilibrium constant K ? 100. This process is accompanied by an
      increase in the system disorder (DeltaS > 0).

PMID- 25997660
TI  - Ex vivo skin permeation and retention studies on chitosan-ibuprofen-gellan
      ternary nanogel prepared by in situ ionic gelation technique--a tool for
      controlled transdermal delivery of ibuprofen.
AB  - The chemical potentials of drug-polymer electrostatic interaction have been
      utilized to develop a novel ternary chitosan-ibuprofen-gellan nanogel as
      controlled transdermal delivery tool for ibuprofen. The ternary nanogels were
      prepared by a combination of electrostatic nanoassembly and ionic gelation
      techniques. The electrostatic and hydrophobic interactions as well as hydrogen
      bonding between ibuprofen and chitosan were confirmed with FTIR, while DSC, TGA
      and SEM confirmed the physical state, thermal and morphological characteristics,
      respectively. The ex vivo delivery of ibuprofen onto and across the skin was
      evaluated based on system specific drug release parameters such as steady state
      permeation rate, permeability coefficient, permeability enhancement ratio,
      skin/gel partition coefficient, diffusion coefficient, lag time and release rate
      constant and mechanisms of release were determined using mathematical models.
      Interaction between ibuprofen and chitosan produced new spherical eutectic
      nanoconjugates with remarkable decrease in particle size of ibuprofen from 4580
      (length-to-breadth aspect ratio) to a minimum of 14.15 nm (324-times), and
      thermally stable amorphous characteristics. The nanogels exhibited significant
      elastic and pseudoplastic characteristics dictated by the concentration of
      chitosan with maximum swelling capacity of 775% w/w at 6.55 mM chitosan compared
      with 281.16 and 506.50% for plain gellan and control ibuprofen hydrogel,
      respectively. Chitosan enhanced the skin penetration, permeability and the rate
      of transdermal release of ibuprofen by a factor of 4, dictated by the extent of
      ibuprofen-chitosan ionic interaction and its concentration. The major mechanism
      of ibuprofen release through the pig skin was drug diffusion however drug
      partition and matrix erosion also occurred. It was evident that ternary nanogels
      are novel formulations with potential application in controlled transdermal
      delivery of ibuprofen.

PMID- 25997662
TI  - Doxorubicin loaded magnetic gold nanoparticles for in vivo targeted drug
      delivery.
AB  - Treatment of approximately 50% of human cancers includes the use of chemotherapy.
      The major problem associated with chemotherapy is the inability to deliver
      pharmaceuticals to specific site of the body without inducing normal tissue
      toxicity. Latterly, magnetic targeted drug delivery (MTD) has been used to
      improve the therapeutic performance of the chemotherapeutic agents and reduce the
      severe side effects associated with the conventional chemotherapy for malignant
      tumors. In this study, we were focused on designing biocompatible magnetic
      nanoparticles that can be used as a nanocarrier's candidate for MTD regimen.
      Magnetic gold nanoparticles (MGNPs) were prepared and functionalized with thiol
      terminated polyethylene glycol (PEG), then loaded with anti-cancer drug
      doxorubicin (DOX). The physical properties of the prepared NPs were characterized
      using different techniques. Transmission electron microscopy (TEM) revealed the
      spherical mono-dispersed nature of the prepared MGNPs with size about 22 nm.
      Energy dispersive X-ray spectroscopy (EDX) assured the existence of both iron and
      gold elements in the prepared nanoparticles. Fourier transform infrared (FTIR)
      spectroscopy assessment revealed that PEG and DOX molecules were successfully
      loaded on the MGNPs surfaces, and the amine group of DOX is the active attachment
      site to MGNPs. In vivo studies proved that magnetic targeted drug delivery can
      provide a higher accumulation of drug throughout tumor compared with that
      delivered by passive targeting. This clearly appeared in tumor growth inhibition
      assessment, biodistribution of DOX in different body organs in addition to the
      histopathological examinations of treated and untreated Ehrlich carcinoma. To
      assess the in vivo toxic effect of the prepared formulations, several biochemical
      parameters such as aspartate aminotransferase (AST), alanine transaminase (ALT),
      lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), urea, uric acid and
      creatinine were measured. MTD technology not only minimizes the random
      distribution of the chemotherapeutic agents, but also reduces their side effects
      to healthy tissues, which are the two primary concerns in conventional cancer
      therapies.

PMID- 25997663
TI  - Endovascular Occlusion of Cervical Internal Carotid Artery Pseudoaneurysm in a
      Child Treated by N-Butyl Cyanoacrylate: A Rare Case Report.
AB  - We report a rare case of spontaneous extracranial cervical internal carotid
      artery (ICA) pseudoaneurysm in a female child aged 3 years who presented with a
      swelling in the neck which had bled following an attempted incision as it had
      been thought to be an abscess. A CT angiogram and an MR angiogram were not very
      conclusive to diagnose the exact site of origin and the morphology of the
      aneurysm. Digital subtraction angiography revealed a dissecting pseudoaneurysm of
      the right extracranial cervical ICA. The right ICA was ending as a pseudosac, and
      the right cerebral circulation was filling up through the right posterior
      cerebral artery. To minimize the radiation exposure, a microcatheter was placed
      inside the diagnostic catheter. The aneurysm sac was occluded using N-butyl
      cyanoacrylate since there was no distal flow to the brain from the artery beyond
      the aneurysm. It was a safe, effective and cheaper alternative to open surgery or
      to other endovascular management options available. Not all neck swellings are
      abscesses, and they should be examined and evaluated to exclude a vascular cause.

PMID- 25997664
TI  - S1 guideline on occupational skin products: protective creams, skin cleansers,
      skin care products (ICD 10: L23, L24)--short version.
AB  - Job-related hand dermatitis heads up the list of reported occupational diseases.
      So-called skin products - understood to mean protective creams, skin cleansers
      and skin care products - are used for the primary and secondary prevention of job
      related hand dermatitis. In the interests of evidence-based medicine, the only
      preventive measures and/or occupational skin products that should be used are
      those whose potential uses and efficacy are underpinned by scientific research.
      To this end, the Arbeitsgemeinschaft fur Berufs- und Umweltdermatologie e.V.
      (Working Group for Occupational and Environmental Dermatology, ABD) of the DDG
      (German Dermatological Society) and the Deutsche Gesellschaft fur Arbeits- und
      Umweltmedizin (German Society for Occupational and Environmental Medicine, DGAUM)
      have summed up the latest scientific findings and recommendations in the updated
      guideline. The benefit of the combined application of protective creams and skin
      care products in the primary and secondary prevention of work-related contact
      dermatitis has been widely confirmed by recent clinical-epidemiological studies.
      The guideline clearly explains the necessity of demonstrating the efficacy of
      protective creams and cleansing products by means of in vivo methods in the sense
      of repetitive applications. Transferable standardised testing systems designed to
      examine the irritation potential and thus the compatibility of occupational skin
      cleansers and the reduction of irritation by protective skin creams have now been
      developed and validated by multicentre studies for skin protection creams and
      cleansers. The status of the current assessment of the safety of occupational
      skin products is also summarised.

PMID- 25997665
TI  - The Hybrid Submental Flap for Tongue Reconstruction.
AB  - PURPOSE: To describe a hybrid submental flap using pedicled and microvascular
      techniques to circumvent a restricting vascular anatomy and increase the
      rotational arc of the skin paddle. METHODS AND MATERIALS: This case report and
      literature review describes a hybrid submental flap. A standard submental island
      flap was planned and elevated for reconstruction of an acquired lateral tongue
      defect secondary to oncologic ablation. Aberrant venous anatomy was encountered
      in which the submental vein drained directly into the internal jugular vein, thus
      limiting the arc of rotation. The facial vein was ligated at its branch point
      from the internal jugular vein and anastomosed to the external jugular vein.
      Medical records were reviewed, including clinical and operative notes. A standard
      free flap postoperative protocol was adhered to, including aspirin, enoxaparin
      sodium, flap checks, and internal monitoring using a venous Flow Coupler (Synovis
      Micro Companies Alliance, Inc, Birmingham, AL). RESULTS: The hybrid submental
      flap was used effectively for lateral tongue reconstruction. Hybridization of the
      flap allowed for increased pedicle length and mobilization of the skin paddle.
      The flap remained well perfused postoperatively, with excellent speech and
      swallow function after adjuvant chemoradiotherapy. CONCLUSION: The hybrid
      submental flap is technically feasible and can be a valuable bailout procedure
      when aberrant vascular anatomy limits the arc of rotation. Ligation and
      anastomosis of the vein, versus the artery, is more likely to be required because
      of the more variable drainage patterns and potential valves that would prevent
      retrograde flow in a Y-V procedure. Retrograde arterial perfusion through the
      angular branch of the facial artery, by ligation of the submental artery at its
      proximal takeoff from the facial artery, is a well-documented method to gain
      cephalad arc of rotation in cases of restrictive arterial anatomy.

PMID- 25997666
TI  - A Case Report of a Vallecular Cyst and Literature Review.
AB  - Cysts in the vallecula are rare entities and seldom have been reported in the
      literature. However, these masses can have very important clinical implications.
      When they are small, they are usually asymptomatic. When they reach a large
      enough size, they can cause dysphagia, odynophagia, and acute airway
      complications. With the expanded scope of oral and maxillofacial surgery, the
      proper diagnosis and management of vallecular lesions could become a routine part
      of oral and maxillofacial surgical practice and aid in further development of the
      specialty. This report describes the case of a benign lymphoepithelial cyst of
      the vallecula. 

PMID- 25997667
TI  - Lymphoepithelial Carcinoma of the Sublingual Gland: Case Report and Review of the
      Literature.
AB  - Lymphoepithelial carcinoma represents only 0.4% of salivary gland neoplasms.
      Generally affecting the parotid gland, it has been reported only twice in the
      sublingual gland. Controversies concerning the treatment of lymphoepithelial
      carcinoma exist. Although the literature generally agrees that primary surgery
      with adjuvant radiotherapy is part of the treatment, the benefit of adjuvant
      chemotherapy is not well described. This report describes the case of a 55-year
      old man diagnosed with lymphoepithelial carcinoma of the sublingual gland. The
      patient was admitted for progressive pain in the floor of the mouth associated
      with trismus. Biopsy examination confirmed the diagnosis of lymphoepithelial
      carcinoma of the sublingual gland and magnetic resonance imaging showed multiple
      left lymphadenopathies. Surgery consisted of a radical neck dissection type III,
      surgical resection of the floor of the mouth, and reconstruction with a left
      facial artery musculomucosal flap. The patient received adjuvant radiotherapy (60
      Gy) and adjuvant chemotherapy (3 cycles of cisplatinum 100 mg/m(2)). The patient
      was disease free at 36 months of follow-up. The evidence base for administering
      adjuvant chemotherapy in this situation is discussed.

PMID- 25997668
TI  - The Faculty Educator Development Award: A 12-Year Perspective on Success,
      Excellence, and Impact on the Specialty of Oral and Maxillofacial Surgery.

PMID- 25997669
TI  - Synthesis of fluorosugar reagents for the construction of well-defined
      fluoroglycoproteins.
AB  - 2-Deoxy-2-fluoroglycosyl iodides are privileged glycosyl donors for the
      stereoselective preparation of 1-Nu-beta-fluorosugars, which are useful reagents
      for chemical site-selective protein glycosylation. Ready access to such beta
      fluorosugars enables the mild and efficient construction of well-defined
      fluoroglycoproteins. 

PMID- 25997670
TI  - Expression of SPARC and the osteopontin-like protein during skeletal development
      in the cichlid fish Oreochromis mossambicus.
AB  - BACKGROUND: Bones are mainly composed of calcium hydroxyapatite and a proteinous
      matrix. In this study, we focus on the bone matrix proteins, the fish osteopontin
      orthologous protein (osteopontin-like protein; OP-L) and SPARC, because the
      current knowledge regarding their expression is fragmentary or contradictory.
      RESULTS: We first provide a comprehensive and detailed description of skeletal
      development in the cichlid fish Oreochromis mossambicus. Following this, we
      analyzed the expression pattern of OP-L and SPARC in detail during development.
      OP-L expression was only found in tissues that undergo ossification (i.e.,
      developing bones and teeth). Furthermore, we show that there is a fundamental
      difference in cartilage formation of the splanchnocranium and all other
      cartilages, concerning SPARC expression. Significantly, we show that the initial
      calcification of cranial bones occurs simultaneously with the expression of OP-L
      and SPARC in the osteoblast-like cells, which appear early in development.
      CONCLUSIONS: The difference in SPARC expression during chondrogenesis of the
      splanchnocranium is likely based on its different evolutionary history compared
      with the dermatocranium and chondrocranium. Moreover, our results suggest a co
      occurrence of the initial calcium deposition and bone matrix protein expression
      during osteogenesis. Overall, this study enhances our understanding of fish
      skeletal development and evolution.

PMID- 25997671
TI  - A guide to mechanobiology: Where biology and physics meet.
AB  - Cells actively sense and process mechanical information that is provided by the
      extracellular environment to make decisions about growth, motility and
      differentiation. It is important to understand the underlying mechanisms given
      that deregulation of the mechanical properties of the extracellular matrix (ECM)
      is implicated in various diseases, such as cancer and fibrosis. Moreover, matrix
      mechanics can be exploited to program stem cell differentiation for organ-on-chip
      and regenerative medicine applications. Mechanobiology is an emerging
      multidisciplinary field that encompasses cell and developmental biology,
      bioengineering and biophysics. Here we provide an introductory overview of the
      key players important to cellular mechanobiology, taking a biophysical
      perspective and focusing on a comparison between flat versus three dimensional
      substrates. This article is part of a Special Issue entitled: Mechanobiology. 

PMID- 25997672
TI  - Cochlear implants as a treatment option for unilateral hearing loss, severe
      tinnitus and hyperacusis.
AB  - Tinnitus is an incapacitating condition commonly affecting cochlear implant (CI)
      candidates. The aim of this clinical study is to assess the long-term effects of
      CI treatment in patients with severe-to-profound, sensorineural, unilateral
      hearing loss (UHL) and incapacitating tinnitus. We performed a prospective
      CochlearTM company-sponsored multicentre study in five Spanish centres. Sixteen
      patients with UHL and incapacitating tinnitus, which was indicated by a Tinnitus
      Handicap Inventory (THI) score >58%, received a Nucleus(r) CI in their deaf ear.
      The study design includes repeated within-subject measures on hearing, tinnitus,
      hyperacusis and quality of life up to 12 months after initial CI fitting. In
      addition to hearing loss and tinnitus, all patients suffered from hyperacusis.
      Most patients had a sudden hearing loss and received a CI within 2 years after
      their hearing loss. Preliminary 6-month, post-CI activation data of 13 subjects
      showed that the majority of patients perceived a subjective benefit from CI
      treatment, which was assessed using the THI, a Visual Analogue Scale of tinnitus
      loudness/annoyance and the Speech, Spatial and Qualities of Hearing Scale.
      Preliminary 12-month data of 7 subjects showed that most patients also perceived
      a degree of relief from their hyperacusis. One patient showed no improvements in
      any of the applied scales, which could be explained by partial insertion of the
      electrode due to obstruction of the cochlea by otosclerosis. In conclusion, CI
      can successfully be used in the treatment of UHL patients with accompanying
      severe tinnitus and hyperacusis. Implantation resulted in hearing benefits and a
      durable relief from tinnitus and hyperacusis in the majority of patients. These
      findings support the hypothesis that pathophysiological mechanisms after
      peripheral sensorineural hearing loss are at least partly reversible when hearing
      is restored with a CI.

PMID- 25997673
TI  - Redefining risk categories for pneumococcal disease in adults: critical analysis
      of the evidence.
AB  - OBJECTIVE: To analyze the available published data (2005-2014) describing the
      prevalence of multimorbidity in adult patients with pneumococcal disease, with a
      focus on the comorbidities considered by the Advisory Committee on Immunization
      Practices (ACIP) of the US Centers for Disease Control and Prevention to increase
      the risk of pneumococcal disease in adults (immunocompetent persons with chronic
      medical conditions (at risk) and immunocompromised or immunosuppressed persons
      (high risk)). An analysis of case-control and population-based surveillance
      studies that have evaluated risk factors for community-acquired pneumonia (CAP)
      and invasive pneumococcal disease (IPD) was also performed in order to estimate
      the importance of risk stacking. METHODS: Studies that established the enrolment
      procedure for patients and reported the incidence of multimorbidity and risk
      factors for CAP and/or IPD were included. In order to obtain a risk stacking
      value based on the at-risk comorbidity odds ratios (OR), the multiplicative
      method described by Campbell was used. RESULTS: Thirty-eight articles were
      selected, 19 for multimorbidity and 19 for risk factors for CAP/IPD. With regard
      to multimorbidity, the prevalence among adults aged >=65 years ranged from 23% to
      98.7% for two or more comorbidities and from 18% to 89.7% for three or more
      comorbidities. Diabetes (DBT), chronic heart disease (CHD), and chronic
      obstructive pulmonary disease (COPD) were the three most frequent comorbidities
      described (7.6-28.5%, 6.9-25.8%, and 3.8-15.4%, respectively). With regard to
      risk factors, based on the multiplicative method, the hypothetical scenario of
      concurrence of the three most frequent at-risk conditions (DBT+CHD+COPD) showed
      an OR of >=7.5. In this group of patients, the addition of smoking, another
      common at-risk factor for CAP (stacking four concurrent conditions) increased the
      OR from 8.5 to >40. These ORs were generally similar to rates described by other
      authors in persons with a high risk. CONCLUSIONS: The ORs for CAP and IPD of
      patients with two or more comorbidities, with or without smoking, were found to
      be similar to the ORs for CAP and IPD described in the literature for patients
      currently classified as high risk. The potential impact of multiple, stacking
      comorbidities is underestimated and there is a need for the risk categories for
      pneumococcal disease to be redefined.

PMID- 25997675
TI  - X-FISH: Analysis of cellular RNA expression patterns using flow cytometry.
AB  - Fluorescent in situ hybridization (FISH) is a powerful technique for the
      detection of RNA or DNA within cells and tissues, which provides a unique link
      between molecular and cell biology. This technique is broadly applicable across a
      range of biological systems. While FISH has been previously adapted to flow-based
      platforms, their use remains limited because of procedural challenges and costs
      associated with commercial kits. Herein we present a protocol that modifies
      existing techniques to sensitively and specifically detect and examine RNA
      expression patterns in primary cells and cell lines using flow cytometry
      (expression-FISH; X-FISH). As relevant examples, we show how this technique can
      be used to monitor changes in mRNA expression following activation, how it can be
      combined with antibody staining to study RNA and protein in the same sample, and
      how it can help distinguish among subsets in a mixed cell population. X-FISH can
      integrate multiple probes and can be performed in conjunction with other assays,
      allowing for informative multiparametric analyses and increased statistical
      robustness. For non-classical comparative animal models this procedure provides a
      time saving alternative to de novo production of antibody-based markers. Finally,
      X-FISH provides an economical solution that is applicable to conventional as well
      as multi-spectral imaging flow cytometry platforms. 

PMID- 25997674
TI  - Risk Factors for Relapse and Higher Costs Among Medicaid Members with Opioid
      Dependence or Abuse: Opioid Agonists, Comorbidities, and Treatment History.
AB  - Clinical trials show that opioid agonist therapy (OAT) with methadone or
      buprenorphine is more effective than behavioral treatments, but state
      policymakers remain ambivalent about covering OAT for long periods. We used
      Medicaid claims for 52,278 Massachusetts Medicaid beneficiaries with a diagnosis
      of opioid abuse or dependence between 2004 and 2010 to study associations between
      use of methadone, buprenorphine or other behavioral health treatment without OAT,
      and time to relapse and total healthcare expenditures. Cox Proportional Hazards
      ratios for patients treated with either methadone or buprenorphine showed
      approximately 50% lower risk of relapse than behavioral treatment without OAT.
      Expenditures per month were from $153 to $233 lower for OAT episodes compared to
      other behavioral treatment. Co-occurring alcohol abuse/dependence quadrupled the
      risk of relapse, other non-opioid abuse/dependence doubled the relapse risk and
      severe mental illness added 80% greater risk compared to those without each of
      those disorders. Longer current treatment episodes were associated with lower
      risk of relapse. Relapse risk increased as prior treatment exposure increased but
      prior treatment was associated with slightly lower total healthcare expenditures.
      These findings suggest that the effectiveness of OAT that has been demonstrated
      in clinical trials persists at the population level in a less controlled setting
      and that OAT is associated with lower total healthcare expenditures compared to
      other forms of behavioral treatment for patients with opioid addiction. Co
      occurring other substance use and mental illness exert strong influences on cost
      and risk of relapse, suggesting that individuals with these conditions need more
      comprehensive treatment. 

PMID- 25997676
TI  - Differences in the whole saliva baseline proteome profile associated with
      development of oral mucositis in head and neck cancer patients undergoing
      radiotherapy.
AB  - Oral mucositis (OM) is a common, painful and often treatment-limiting side effect
      of radiotherapy (RT) for head and neck cancer (HNC) patients. Unstimulated saliva
      was collected before the first radiotherapy application in 50 HNC patients. 41
      out of 50 patients developed OM (grade III) during radiotherapy, of which 14
      patients even displayed an early OM (grade III) at a low radiation dose of 30Gy.
      Nine patients did not develop OM (grade III). Using an LC-MS/MS approach 5323
      tryptic peptides were assigned to 487 distinct proteins (>=2 peptides) in the
      data set. The levels of 48 proteins differed significantly (p<0.05) between
      patients developing OM or not. 17 proteins displayed increased levels (>=1.3
      fold) and 31 proteins decreased in level in OM, respectively. Furthermore, using
      partial least square analysis protein patterns could be used to distinguish
      subjects which did not develop grade III OM even after 70Gy total dose (n=9) and
      those displaying early OM (grade III at <30Gy total dose, n=14). Using leave one
      out cross validation 37 of 41 patients (90%) developing OM could be correctly
      assigned indicating that prognostic proteome signatures may help identify
      patients that should be specifically monitored to increase overall effectiveness
      of RT treatment. 

PMID- 25997677
TI  - UV-B stress induced metabolic rearrangements explored with comparative proteomics
      in three Anabaena species.
AB  - Comparative proteomics together with physiological variables revealed different
      responses among three species of diazotrophic cyanobacterium Anabaena exposed to
      UV-B stress at the same time points. Perceptible decline in PSII activity, ATP
      pool, nitrogenase activity and respiration rate was observed for all the three
      species; this being maximum in Anabaena doliolum, followed by Anabaena sp. PCC
      7120 and minimum in Anabaena L31. Statistical analysis of the protein abundance
      divided majority of them as early accumulated in A. L31, late accumulated in A.
      sp. PCC 7120 and downregulated in A. doliolum. Tolerance of A. L31 may be
      ascribed to post-translational modification reflected through the highest number
      of protein isoforms in its proteome followed by A. PCC 7120 and A. doliolum.
      Furthermore, increase in abundance of cyanophycinase, glutamine synthetase and
      succinate semialdehyde dehydrogenase in A. L31 suggests operation of an alternate
      pathway for assimilation of nitrogen and carbon under UV-B stress. An early
      accumulation of four proteins viz., glutamate ammonia ligase (Alr2328),
      transketolase (Alr3344), inorganic pyrophosphatase (All3570), and trigger protein
      (Alr3681) involved respectively in amino acid metabolism, energy metabolism,
      biosynthesis of cofactor and trigger protein and chaperone like activity across
      three species, suggests them to be marker of UV-B stress in Anabaena spp. This
      article is part of a Special Issue entitled: Proteomics in India.

PMID- 25997678
TI  - Enhanced enterovirus 71 virus-like particle yield from a new baculovirus design.
AB  - Enterovirus 71 (EV71) is responsible for the outbreaks of hand-foot-and-mouth
      disease in the Asia-Pacific region. To produce the virus-like particle (VLP)
      vaccine, we previously constructed recombinant baculoviruses to co-express EV71
      P1 polypeptide and 3CD protease using the Bac-to-Bac((r)) vector system. The
      recombinant baculoviruses resulted in P1 cleavage by 3CD and subsequent VLP
      assembly in infected insect cells, but caused either low VLP yield or excessive
      VLP degradation. To tackle the problems, here we explored various expression
      cassette designs and flashBAC GOLDTM vector system which was deficient in v-cath
      and chiA genes. We found that the recombinant baculovirus constructed using the
      flashBAC GOLDTM system was insufficient to improve the EV71 VLP yield.
      Nonetheless, BacF-P1-C3CD, a recombinant baculovirus constructed using the
      flashBAC GOLD(TM) system to express P1 under the polh promoter and 3CD under the
      CMV promoter, dramatically improved the VLP yield while alleviating the VLP
      degradation. Infection of High Five(TM) cells with BacF-P1-C3CD enhanced the
      total and extracellular VLP yield to ~268 and ~171 mg/L, respectively, which
      enabled the release of abundant VLP into the supernatant and simplified the
      downstream purification. Intramuscular immunization of mice with 5 MUg purified
      VLP induced cross-protective humoral responses and conferred protection against
      lethal virus challenge. Given the significantly improved extracellular VLP yield
      (~171 mg/L) and the potent immunogenicity conferred by 5 MUg VLP, one liter High
      Five(TM) culture produced ~12,000 doses of purified vaccine, thus rendering the
      EV71 VLP vaccine economically viable and able to compete with inactivated virus
      vaccines.

PMID- 25997680
TI  - The Overuse, Underuse, and Misuse of Dialysis in ESKD Patients with Dementia.
AB  - The profile of patients on chronic dialysis has shifted. There is a growing group
      of older patients with comorbid dementia and ESKD, who are at risk of overuse,
      underuse, and misuse of dialysis. Policy is lacking to help guide treatment
      decisions in this group. This paper explores clinical considerations specific to
      patients with comorbid ESKD and dementia. These include: the impact of comorbid
      dementia on dialysis effectiveness and feasibility; burden of care issues that
      are specific to patients with dementia; and capacity, autonomy, and consent. A
      better understanding of these issues may help guide discussions and decision
      making about treatment. For some older patients with multiple comorbidities
      including dementia, dialysis does not provide survival or quality of life benefit
      compared to medical management. These patients also experience additional
      treatment burden due to a 'dementia unfriendly' environment. However, exceptions
      may include patients who are younger, more independent, and have fewer
      comorbidities. Patients with dementia are often inappropriately assumed to lack
      capacity to participate in treatment decision making, and are at risk of having
      their preferences overlooked. Many patients with mild-to-moderate dementia remain
      capable of reporting their preferences and quality of life, and should always be
      involved in treatment discussions where possible. 

PMID- 25997679
TI  - miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in
      Crohn's disease.
AB  - Although aberrant microRNA (miRNA) expression has frequently been observed in
      inflammatory bowel disease (IBD), its biological functions and targets remain
      largely unknown. Present study found that miR-19b was significantly downregulated
      in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of
      cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive
      immunity that controls several immuno-inflammatory diseases, was predicted to be
      a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3
      protein levels, but not mRNA, was identified in active-CD intestinal tissue
      samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29
      cells, it was experimentally validated that miR-19b is a direct regulator of
      SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly
      recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore,
      overexpression of miR-19b decreased SOCS3 expression, leading to increased
      production of macrophage-inflammatory protein-3alpha (MIP-3alpha) in Caco2 cells.
      In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3alpha.
      Finally, intracolonically delivered miR-19b decreased the severity of colitis
      induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our
      findings suggest that miR-19b suppresses the inflammatory response by inhibiting
      SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and
      thereby prevents the pathogenesis of CD. 

PMID- 25997682
TI  - [Predictive factors for visual outcome after corneal collagen crosslinking
      treatment in progressive keratoconus: One-year refractive and topographic
      results].
AB  - PURPOSE: To assess the effects of preoperative patient characteristics on
      clinical outcomes of corneal collagen crosslinking (CXL) in patients with
      progressive keratoconus. PATIENTS AND METHODS: Fifty-four eyes of 41 patients
      underwent CXL for progressive keratoconus between June 2011 and December 2012.
      Corneal topography (Orbscan((r))) was assessed at 1, 3, and 6 months and 1 year
      after CXL treatment and compared with preoperative data. RESULTS: A significant
      improvement in 1-year postoperative best-corrected visual acuity (BCVA) (0.16+/
      0.21 LogMar preoperatively versus 0.09+/-0.16 LogMar postoperatively, P=0.007)
      and in 3mm topographic central irregular astigmatism (P=0.04) was demonstrated
      with CXL. No significant change was noted for refractive astigmatism (P=0.69), or
      for 1-year postoperative Kmax (48.4 D+/-4.1 at baseline versus 48.5 D+/-4.1
      postoperatively, P=0.46). Predictive factors for BVCA improvement were low
      preoperative BCVA, high refractive astigmatism and advanced keratoconus.
      Predictive factors for stability of postoperative Kmax values were early
      keratoconus, and central cone ("nipple" morphology of the cone mainly located in
      the central 3mm of the cornea). CONCLUSION: This retrospective study confirms the
      efficacy of CXL for progressive keratoconus, from a refractive as well as
      topographic standpoint. While cone localization or its eccentricity seems to
      explain the variability of CXL efficacy reported in the literature, cone severity
      appears to be the main predictive factor for a lack of topographic stability
      after CXL treatment but must be weighted by the preferential localization of the
      cone (3 or 5mm central corneal zone).

PMID- 25997681
TI  - [Interest of optical coherence tomography performed immediately before
      intravitreal injection of anti-VEGF in exudative AMD].
AB  - INTRODUCTION: Two or three systematic intravitreal injections (IVT) may be
      prescribed in a PRN approach to treat an exudative recurrence of neovascular age
      related macular degeneration (AMD), according to the phenotype. Optical coherence
      tomography (OCT) may be performed immediately before the 2nd or the 3rd scheduled
      IVT, making it possible to cancel the procedure in the absence of exudation. The
      aim of the study was to evaluate the usefulness of this OCT examination and to
      assess the percentage of IVT cancelled, in order to evaluate a potential medico
      economic benefit. METHODS: Monocentric retrospective study, in which were
      included 292 consecutive eyes with exudative recurrence of AMD, for which 2 or 3
      IVT were scheduled between January 1st and April 30th, 2014. All patients
      received a first systematic IVT in the seven days following the diagnosis. Then,
      on the days of the 2nd and 3rd scheduled IVT, each patient had a visual acuity
      measurement and a Spectral domain-OCT (Spectralis, HRA Heidelberg Engineering).
      This measurement allowed for the IVT to be either performed as scheduled or
      cancelled. Both ranibizumab and aflibercept were used. A Chi(2) test was used to
      compare the qualitative variables and an adjusted Wilcoxon test for the
      quantitative values. RESULTS: Two hundred and ninety-two consecutive eyes were
      included; 172 in the "2 scheduled IVT" group (group A) and 120 in the "3
      scheduled IVT" group (group B). At the first follow-up, 37.6% of scheduled IVT
      were cancelled after the OCT (44.1% in group A and 28.3% in group B). At the
      second follow-up, 33.3% of IVT were cancelled in group B. Overall, 150/412
      (36.4%) IVT were avoided in this series. Presence of serous retinal detachment,
      retinal edema and increased central macular thickness were statistically
      correlated with confirmation of the scheduled IVT at the two follow-ups (P<0.001,
      P<0.001 and P=0.002, respectively). A savings of 429.80 ? per patient was
      calculated during this short period of follow-up. CONCLUSION: An average non
      injection rate of 36.4% of scheduled IVT was found in this protocol of management
      of recurrences with OCT performed the day of IVT. This protocol allowed to avoid
      unnecessary IVT one-third of the time and appeared highly cost-effective.

PMID- 25997683
TI  - [Removal of a Miragel((r)) fragment by emulsification].

PMID- 25997684
TI  - [Upper eyelid reconstruction with the Cutler-Beard flap technique: Retrospective
      study of 16 cases].
AB  - OBJECTIVES: Large, full thickness upper eyelid defects are still difficult to
      deal with in oculoplastic surgery. High specificity in the anatomy and function
      of the upper eyelid shows how difficult reconstruction can be. We aimed to assess
      the results provided by the Cutler-Beard flap technique. METHODS: We conducted a
      retrospective study of all patients who had undergone Cutler-Beard flap
      reconstruction in the Oculoplastic service of La Fondation Rothschild in Paris,
      from January 2008 to June 2013. Sixteen patients were included. RESULTS: Fifteen
      flaps remained viable during the follow-up examinations. Opening, occlusion and
      palpebral position were very satisfactory in 11, 12 and 11 cases respectively.
      The ocular surface was preserved in 8 cases and exhibited only mild alterations
      in 5 cases. The average aesthetic result was noted 2/3 for 11 patients with
      postoperative photographs. We did not observe any relapses with oncologic
      indications. CONCLUSIONS: Upper eyelid reconstruction by the Cutler-Beard flap
      technique appears to provide good functional and aesthetic restoration in the
      majority of cases. In the others, a simple additional surgery under local
      anaesthetic and/or sedation provides adequate correction in most instances.

PMID- 25997685
TI  - A 14-Year Experience in the Management of Patients with Acquired Immune
      Thrombotic Thrombocytopenic Purpura in Northern Israel.
AB  - Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life
      threatening microangiopathic disorder usually treated with therapeutic plasma
      exchange (TPE). The current study assessed the role of rituximab in the treatment
      of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP
      patients treated with TPE and a cohort of refractory or relapsed patients who
      also received rituximab. This retrospective evaluation included 45 I-TTP
      patients, treated between January 2000 and October 2013, who underwent at least 3
      TPE procedures and were followed up until December 2013 or death. Thirty-one
      patients with an uncomplicated course received TPE only. Fourteen patients had a
      complicated course due to either a primary refractory/exacerbated disease (n = 5)
      or relapse (n = 9) and received rituximab together with TPE. The median number of
      TPE procedures performed in the first TTP episode in the uncomplicated cohort and
      groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively.
      The relapse rates per follow-up year in the uncomplicated I-TTP, primary
      refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes,
      respectively. After rituximab therapy this rate dropped to 0.2 per year in the
      relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a
      complicated course and experienced a major benefit from rituximab in terms of
      effectiveness and safety. 

PMID- 25997686
TI  - The effect of enhanced recovery program for patients undergoing partial
      laparoscopic hepatectomy of liver cancer.
AB  - OBJECTIVE: To analyze the results after the introduction of enhanced recovery
      after surgery (ERAS) protocols, a randomized study was performed to compare the
      outcomes of laparoscopic hepatectomy under ERAS or traditional care. METHODS:
      Patients undergoing laparoscopic hepatectomy from April 2014 to October 2014 were
      included and randomly divided into Control group (CG) and ERAS. Primary outcome
      was quality of life (QoL) and length of hospital stay (LOS). Secondary endpoints
      were percentage readmission, mortality, duration to first flatus, complications,
      hospital costs, conversions and blood loss. RESULTS: Thirteen patients withdrew
      after randomization. Eighty-six patients completed the study, 48 ERAS and 38 CG.
      Postoperative LOS was significantly reduced in ERAS [6 (4-8) versus 10 (7-15)
      days, P = 0.04]. First flatus occurred earlier in ERAS than CG [2(1-4) versus 3(2
      5) days, P = 0.02]. The average perioperative charges were 9470 +/- 1540 in CG
      and only 7742 +/- 1200 in ERAS (P = 0.03), with no differences in readmission
      rate, blood loss, conversions to open surgery, mortality or surgical
      complications. The median AUC (area under a curve) of QoL was considerably
      improved in ERAS (P = 0.04). CONCLUSIONS: This study suggests that ERAS is
      feasible and safe for laparoscopic hepatectomy.

PMID- 25997687
TI  - RAS status in Korean patients with stage III and IV colorectal cancer.
AB  - BACKGROUND: KRAS mutations are common and clearly contribute to malignant
      progression. The frequency of NRAS mutations and their relationship to clinical,
      pathologic, and molecular features remains unclear. METHODS: We evaluated 130
      colorectal tumors for mutations in KRAS and NRAS gene. We tested for mutations in
      codons 61 and 146 of KRAS and codons 12, 13, 59, 61 and 146 of NRAS. Mutation
      status was determined by targeted dideoxy sequencing. RESULTS: Among the analyzed
      primary tumors, 36.2% had KRAS mutation. Of the 83 KRAS codon 12 and 13 wild-type
      patients, 7.2% had KRAS codon 61, 146 or NRAS. 40.7% harbored any RAS mutation.
      CONCLUSION: The frequency of other RAS (NRAS and KRAS exon 3, 4) activating
      mutations in colorectal cancers is relatively low in Korean colorectal cancer
      patients.

PMID- 25997689
TI  - Transcutaneous carbon dioxide monitoring to avoid hypercapnia during complex
      catheter ablations: a feasibility study.
AB  - PURPOSE: The aim of this study was to determine if transcutaneous CO(2)
      monitoring (TCO(2)) is feasible to avoid hypercapnia during complex catheter
      ablation. Cumulative analgesic and anxiolytic effects during complex catheter
      ablation can rarely provoke hypoventilation and respiratory complications. End
      tidal CO(2) monitors have limitations in non-ventilated patients, and frequent
      arterial blood gas sampling is impractical. METHODS: Consecutive patients
      undergoing catheter ablation for atrial fibrillation (AF) or ventricular
      tachycardia (VT) received continuous TCO(2) monitoring. Procedural evaluation of
      TCO(2) was performed concomitantly with point-of-care arterial blood gas testing.
      Endpoints included PCO(2) protocol feasibility, TCO(2)/PCO(2) agreement, and
      avoidance of hypercapnia-related procedural complications. RESULTS: Fifty
      patients [AF n = 36 (72 %), VT n = 14 (28 %)] underwent catheter ablation (mean
      221.7 +/- 57.0 min duration, median 41.4 +/- 21.1 min fluoroscopy) in which 6.0
      +/- 2.6 mg midazolam and 449 +/- 225.5 mcg of fentanyl were administered.
      Monitoring protocol implementation was feasible in 50/50 (100 %) cases. Protocol
      driven anesthesia consultation avoided an unplanned intubation in 1 case (2 %)
      and there was only 1 unplanned intubation (2 %) for oxygen desaturation due to
      heart failure without hypercapnia during a VT ablation (TCO(2)/PCO(2) agreement
      <5 mmHg). There were no respiratory or pulseless electrical arrests (0 %) in the
      study. TCO(2) and PCO(2) correlated well (baseline: r = 0.75, p < 0.001; 1 h:r=
      0.72, p < 0.001; 2 h: r = 0.55, p = 0.003; 3 h: r = 0.79, p = 0.02). However,
      desired agreement was lower than expected [baseline: 33/50 (66 %) < 5 mmHg, 48/50
      (96 %) <10 mmHg; 1 h: 29/45 (64 %) < 5 mmHg, 39/45 (87 %) < 10 mmHg; 2 h: 14/26
      (54 %) < 5 mmHg, 22/26 (85 %) < 10 mmHg; 3 h: 7/11 (64 %) < 5 mmHg, 10/11 (91 %)
      < 10 mmHg; >3 h: 1/3 (33 %) < 5 mmHg, 2/3 (66 %) < 10 mmHg]. CONCLUSION:
      Transcutaneous CO2 monitoring is feasible during complex catheter ablation and
      correlates with invasively obtained data. However, further development is needed
      to achieve the desired level of agreement.

PMID- 25997688
TI  - Microbial derived surface active compounds: properties and screening concept.
AB  - Biosurfactants are surface-active biomolecules that are produced by a variety of
      microorganisms. They have gained biotechnologist interest for high diversity and
      their efficient action in comparison to synthetic emulsifiers. So, we discussed a
      wide array of screening method based on direct and indirect surface and
      interfacial tension measurements. Also, this review describes biosurfactant
      physicochemical properties and natural role in the environment. Also, it presents
      their tolerance to extreme conditions of temperature, pH and ionic strength, low
      toxicity and biodegradability. Functional properties like emulsification,
      foaming, solubilizing and membrane permeabilizing activities were also discussed
      along with their related application. 

PMID- 25997691
TI  - Surgical workload of a foreign medical team after Typhoon Haiyan.
AB  - BACKGROUND: On 8 November 2013, Typhoon Haiyan struck the Philippines causing
      widespread loss of lives and infrastructures. At the request of the Government of
      the Philippines, the Australian Government deployed a surgical field hospital to
      the city of Tacloban for 4 weeks. This paper describes the establishment of the
      hospital, the surgical workload and handover to the local health system upon the
      end of deployment. METHODS: A Microsoft excel database was utilized throughout
      the deployment, recording demographics, relationship to the typhoon and surgical
      procedure performed. RESULTS: Over the 21 days of surgical activity, the
      Australian field hospital performed 222 operations upon 131 persons. A mean of
      10.8 procedures were performed per day (range 3-20). The majority (70.2%) of
      procedures were soft tissue surgery. Diabetes was present in 22.9% and 67.9% were
      typhoon-related. The Australian Medical Assistance Team field hospital adhered to
      the World Health Organization guidelines for foreign medical teams, in ensuring
      informed consent, appropriate anaesthesia and surgery, and worked collaboratively
      with local surgeons, ensuring adequate documentation and clinical handover.
      CONCLUSION: This paper describes the experience of a trained, equipped and
      collaborative surgical foreign medical team in Tacloban in the aftermath of
      Typhoon Haiyan. Sepsis from foot injuries in diabetic patients constituted an
      unexpected majority of the workload. New presentations of typhoon-related
      injuries were presented throughout the deployment.

PMID- 25997690
TI  - Photoswitchable fatty acids enable optical control of TRPV1.
AB  - Fatty acids (FAs) are not only essential components of cellular energy storage
      and structure, but play crucial roles in signalling. Here we present a toolkit of
      photoswitchable FA analogues (FAAzos) that incorporate an azobenzene photoswitch
      along the FA chain. By modifying the FAAzos to resemble capsaicin, we prepare a
      series of photolipids targeting the Vanilloid Receptor 1 (TRPV1), a non-selective
      cation channel known for its role in nociception. Several azo-capsaicin
      derivatives (AzCAs) emerge as photoswitchable agonists of TRPV1 that are
      relatively inactive in the dark and become active on irradiation with ultraviolet
      A light. This effect can be rapidly reversed by irradiation with blue light and
      permits the robust optical control of dorsal root ganglion neurons and C-fibre
      nociceptors with precision timing and kinetics not available with any other
      technique. More generally, we expect that photolipids will find many applications
      in controlling biological pathways that rely on protein-lipid interactions. 

PMID- 25997693
TI  - Is measurement of progesterone level prior to FSH stimulation useful in GnRH
      antagonist cycles?
AB  - AIM: To reduce patient inconvenience during in vitro fertilization (IVF) cycles,
      some protocols delay intensive monitoring until mid-follicular stimulation.
      Others assess hormone levels prior to follicle-stimulating hormone (FSH)
      administration, not commencing stimulation until baseline progesterone (P4)
      levels (< 5 nmol/l) are achieved. Higher P4 levels (> 4.8 nmol/L) on the day of
      FSH trigger have been implicated in poorer pregnancy rates. This study evaluates
      the association of P4 levels at day 1-2 in gonadotrophin-releasing hormone (GnRH)
      antagonist cycles with pre-trigger P4 levels and clinical pregnancy rates (CPRs).
      METHOD: All fresh GnRH-antagonist IVF cycles between June 2011 and June 2012, in
      which pre-FSH P4 levels were not routinely performed (group 1), were retrieved
      from the IVF Australia database and compared with controls (group 2). RESULTS:
      There were 163 cycles in each group. P4 levels on the day of trigger were
      significantly higher in group 1 (3.75 vs. 2.77, p < 0.05). The incidence of pre
      trigger P4 levels >4.8 nmol/l was significantly higher in group 1 (30 vs. 16, p <
      0.05). The number of oocytes retrieved was higher in group 1 (11.1 vs. 9, p <
      0.05), however fertilization rates were significantly lower in that group (53.6%
      vs. 61.2%, p < 0.05); CPRs were similar between the two groups (27.8% vs. 31.8%,
      p = ns). Overall, pregnancy rates were lower in cycles with pre-trigger P4 level
      of > 4.8 nmol/L compared with those with lower levels (15% vs. 32.5%, p < 0.05).
      CONCLUSION: We found that measurement of P4 level at early follicular phase was
      associated with significantly lower pre-trigger levels. However, this did not
      translate into a difference in CPR between the monitored and unmonitored groups.
      We have confirmed that elevation in pre-trigger P4 level is associated with
      halving of the CPR, indicating that the most important P4 measurements are those
      in the late follicular/pre-trigger phase.

PMID- 25997692
TI  - NMR-based metabolomics highlights differences in plasma metabolites in pigs
      exhibiting diet-induced differences in adiposity.
AB  - PURPOSE: A better understanding of the control of body fat mass and distribution
      is required for both human health and animal production. The current study
      investigates plasma parameters in response to changes in body fat mass. METHODS:
      Pigs from two lines divergently selected for residual feed intake were fed diets
      contrasted in energy sources and nutrients. Between 74 and 132 days of age, pigs
      (n = 12 by diet and by line) received isoproteic and isoenergetic diets, either
      rich in starch (LF) or in lipids and fibres (HF). At the end of the feeding
      trial, plasma samples were analysed by (1)H NMR spectroscopy and standard
      hormonal and biochemical assays. RESULTS: Pigs fed the HF diet had lower (P <
      0.01) perirenal and subcutaneous adipose tissue relative masses than pigs fed the
      LF diet. Metabolomic approach showed a clear discrimination between diets, with
      lower (P < 0.05) plasma levels of creatinine-lysine, creatine, tyrosine, proline,
      histidine, lysine, phenylalanine and formate but higher (P < 0.001) plasma VLDL
      LDL levels in HF pigs than in LF pigs. Plasma concentrations of triglycerides
      were higher (P < 0.001), while plasma concentrations of beta-hydroxybutyrate,
      leptin, glucose, insulin and urea were lower (P <= 0.05) in HF pigs than in LF
      pigs. Plasma levels of leptin, creatine and urea were positively correlated (r =
      0.3, P < 0.05) with relative adipose tissue masses. CONCLUSION: These data
      indicate that metabolites associated with energy and protein metabolism were
      involved in the response to a high-fat, high-fibre diet. Relevant plasma
      indicators of metabolic flexibility related to changes in body adiposity were
      then proposed.

PMID- 25997694
TI  - The Prognostic Value of High-Sensitive Troponin I in Stable Coronary Artery
      Disease Depends on Age and Other Clinical Variables.
AB  - OBJECTIVES: To study the prognostic value of high-sensitive troponin (hs-cTn) I
      in stable coronary artery disease. METHODS: In total, we studied 705 patients.
      Secondary outcomes were the incidence of: (1) acute ischemic events and (2) heart
      failure or death. The primary outcome was the composite of them. RESULTS:
      Patients with hs-cTnI >0 ng/ml (62.1%) were older, had a lower estimated
      glomerular filtration rate, more frequent a history of hypertension, atrial
      fibrillation, ejection fraction <40%, and therapy with angiotensin-converting
      enzyme inhibitors, diuretics and acenocumarol. The follow-up period was 2.2 +/-
      0.99 years. Fifty-three patients suffered an acute ischemic event, 33 died or
      suffered heart failure and 78 developed the primary outcome. By univariate Cox's
      regression analysis, hs-cTnI >0 was associated with a higher risk of developing
      the primary outcome [relative risk = 2.360 (1.359-4.099); p = 0.001] and heart
      failure or death [relative risk = 5.932 (1.806-19.482); p < 0.001], but not with
      acute ischemic events. Statistical significance was lost after controlling for
      age. By logistic regression analysis, age [relative risk = 1.026 (1.009-1.044); p
      = 0.003], ejection fraction <40% [relative risk = 4.099 (2.043-8.224); p <
      0.001], use of anticoagulants [relative risk = 2.785 (1.049-7.395); p = 0.040]
      and therapy with angiotensin-converting enzyme inhibitors [relative risk = 1.471
      (1.064-2.034); p = 0.020], and estimated glomerular filtration rate [relative
      risk = 0.988 (0.977-0.999); p = 0.027] were associated with hs-cTnI >0.
      CONCLUSIONS: In stable coronary disease, hs-cTnI is associated with the incidence
      of heart failure or death, but this relationship depends on other variables.

PMID- 25997696
TI  - Location and Electronic Nature of Phosphorus in the Si Nanocrystal--SiO2 System.
AB  - Up to now, no consensus exists about the electronic nature of phosphorus (P) as
      donor for SiO2-embedded silicon nanocrystals (SiNCs). Here, we report on hybrid
      density functional theory (h-DFT) calculations of P in the SiNC/SiO2 system
      matching our experimental findings. Relevant P configurations within SiNCs, at
      SiNC surfaces, within the sub-oxide interface shell and in the SiO2 matrix were
      evaluated. Atom probe tomography (APT) and its statistical evaluation provide
      detailed spatial P distributions. For the first time, we obtain ionisation states
      of P atoms in the SiNC/SiO2 system at room temperature using X-ray absorption
      near edge structure (XANES) spectroscopy, eliminating structural artefacts due to
      sputtering as occurring in XPS. K energies of P in SiO2 and SiNC/SiO2
      superlattices (SLs) were calibrated with non-degenerate P-doped Si wafers.
      results confirm measured core level energies, connecting and explaining XANES
      spectra with h-DFT electronic structures. While P can diffuse into SiNCs and
      predominantly resides on interstitial sites, its ionization probability is
      extremely low, rendering P unsuitable for introducing electrons into SiNCs
      embedded in SiO2. Increased sample conductivity and photoluminescence (PL)
      quenching previously assigned to ionized P donors originate from deep defect
      levels due to P. 

PMID- 25997695
TI  - Epigenetic alterations in gastric cancer (Review).
AB  - Gastric cancer is one of the most common types of cancer and the second most
      common cause of cancer-related mortality worldwide. An increasing number of
      recent studies have confirmed that gastric cancer is a multistage pathological
      state that arises from environmental factors; dietary factors in particulary are
      considered to play an important role in the etiology of gastric cancer. Improper
      dietary habits are one of the primary concerns as they influence key molecular
      events associated with the onset of gastric carcinogenesis. In the field of
      genetics, anticancer research has mainly focused on the various genetic markers
      and genetic molecular mechanisms responsible for the development of this of this
      disease. Some of this research has proven to be very fruitful, providing insight
      into the possible mechamisms repsonsible for this disease and into possible
      treatment modalities. However, the mortality rate associated with gastric cancer
      remains relatively high. Thus, epigenetics has become a hot topic for research,
      whereby genetic markers are bypassed and this research is directed towards
      reversible epigenetic events, such as methylation and histone modifications that
      play a crucial role in carcinogenesis. The present review focuses on the
      epigenetic events which play an important role in the development and progression
      of this deadly disease, gastric cancer. 

PMID- 25997697
TI  - Muscle architecture during the course of development of Diplostomum
      pseudospathaceum Niewiadomska, 1984 (Trematoda, Diplostomidae) from cercariae to
      metacercariae.
AB  - Recent confocal microscopy studies have greatly expanded our knowledge of muscle
      systems in cercariae and adult digeneans, but the gross anatomy and development
      of metacercarial musculature remain relatively little known. To further our
      understanding of metacercarial development, this study used phalloidin staining
      and confocal microscopy to examine changes in muscle architecture over the course
      of development from cercariae to infective metacercariae in Diplostomum
      pseudospathaceum Niewiadomska, 1984. The paper describes muscle development in
      the body wall, anterior organ (oral sucker), acetabulum, pharynx and midgut and
      in the musculo-glandular organs that first appear in metacercariae (lappets and
      holdfast). The muscle architecture of the cercarial tail is also described. The
      results of the study support previously reported observations that diplostomid
      musculature undergoes substantial transformation during metacercarial
      development. The most profound changes, involving extensive remodelling and
      replacement of cercarial muscles, were seen in the body-wall musculature and in
      the anterior organ as it developed into the oral sucker. Muscle systems of other
      cercarial organs showed more gradual changes. The adaptive importance of
      developmental changes in musculature is discussed. 

PMID- 25997698
TI  - [Management of complications in colorectal surgery].

PMID- 25997699
TI  - [Delayed complications after pancreatic surgery: Pancreatic insufficiency,
      malabsorption syndrome, pancreoprivic diabetes mellitus and pseudocysts].
AB  - BACKGROUND: Benign and malignant pathologies of the pancreas can result in a
      relevant chronic disease burden. This is aggravated by morbidities resulting from
      surgical resections as well as from progression of the underlying condition.
      OBJECTIVE: The aim was to summarize the current evidence regarding epidemiology,
      pathophysiology, diagnosis and treatment of endocrine and exocrine pancreatic
      insufficiency, as well as of pancreatic pseudocysts. MATERIAL AND METHODS: A
      selective literature search was performed and a summary of the currently
      available data on the surgical sequelae after pancreatic resection is given.
      RESULTS: Reduction of healthy pancreatic parenchyma down to 10-15 % leads to
      exocrine insufficiency with malabsorption and gastrointestinal complaints. Orally
      substituted pancreatic enzymes are the therapy of choice. Loss of pancreatic
      islets and/or islet function leads to endocrine insufficiency and pancreoprivic
      diabetes mellitus. Inflammatory, traumatic and iatrogenic injuries of the
      pancreas can lead to pancreatic pseudocysts, which require endoscopic,
      interventional or surgical drainage if symptomatic. Finally, pancreatic surgery
      harbors the long-term risk of gastrointestinal anastomotic ulcers, bile duct
      stenosis, portal vein thrombosis and chronic pain syndrome. CONCLUSION: As the
      evidence is limited, an interdisciplinary and individually tailored approach for
      delayed pancreatic morbidity is recommended.

PMID- 25997700
TI  - Interference of STAT 5b expression enhances the chemo-sensitivity of gastric
      cancer cells to gefitinib by promoting mitochondrial pathway-mediated cell
      apoptosis.
AB  - Signal transducer and activator of transcription (STAT) 5, including STAT 5a and
      STAT 5b, was reported to play important roles in the malignant biological
      behaviors of tumors. However, their roles in gastric cancer, especially for STAT
      5b remain unknown. This study aimed to detect the expression of STAT 5b in
      gastric cancer cells and analyze the role and possible mechanism of STAT 5b in
      the chemo-sensitivity of gastric cancer cells to gefitinib. A total of 69
      patients with gastric carcinomas were analyzed for the expression of STAT 5b in
      carcinomas and para-carcinomas by immunohistochemistry. Cultured MGC-803 and MKN
      45 cells were exposed to gefitinib and/or STAT 5b siRNA. Mitochondrial proteins
      including Bcl-2, Bax, caspase-3 and caspase-9 were extracted using special kits
      for detecting mitochondrial pathway-related apoptosis proteins. The results
      showed that STAT 5b expression was significantly increased in gastric carcinomas
      compared with para-carcinomas, with a positive rate of 49/69 in carcinomas and
      27/69 in para-carcinomas (P=0.001). Gefitinib exposure reduced the relative
      viabilities of MGC-803 and MKN-45 cells in a concentration- and time-dependent
      manner, and cell apoptosis increased significantly (P<0.05) with gefitinib
      treatment (4 mM, 24 h). STAT 5b expression was significantly downregulated by
      treatment with gefitinib (4 mM, 24 h). Interference of STAT 5b expression by
      siRNA targeting enhanced the chemo-sensitivity of gastric cancer cells to
      gefitinib by promoting mitochondrial pathway-mediated apoptosis. Bax, caspase-3
      and caspase-9 expression were upregulated, and Bcl-2 expression was downregulated
      in the combined treatment group (gefitinib+siRNA) compared with the gefitinib (4
      mM, 24 h) only group in the MGC-803 and MKN-45 cells (P<0.05). Overall, STAT 5b
      was upregulated in gastric carcinomas compared with para-carcinomas. Interference
      of STAT 5b expression by siRNA targeting enhanced the chemo-sensitivity of
      gastric cancer cells to gefitinib by promoting mitochondrial pathway-mediated
      cell apoptosis. These findings may be useful for developing new approaches for
      the treatment of gastric cancer.

PMID- 25997701
TI  - Iodine promoted alpha-hydroxylation of ketones.
AB  - A novel method for alpha-hydroxylation of ketones using substoichiometric amount
      of iodine under metal-free conditions is described. This method has been
      successfully employed in synthesizing a variety of heterocyclic compounds, which
      are useful precursors. alpha-Hydroxylation of diketones and triketones are
      illustrated. This strategy provides a novel, efficient, mild and inexpensive
      method for alpha-hydroxylation of aryl ketones using a sub-stoichiometric amount
      of molecular iodine. 

PMID- 25997702
TI  - Slug contributes to gemcitabine resistance through epithelial-mesenchymal
      transition in CD133(+) pancreatic cancer cells.
AB  - CD133-positive pancreatic cancer is correlated with unfavorable survival despite
      current development of therapy. Slug acts as a master regulator of epithelial
      mesenchymal transition (EMT) which is the essential process in cancer
      progression. The aim of this study was to investigate the role of Slug in
      gemcitabine treatment for CD133-positive pancreatic cancer cells. We used a
      previously established pancreatic cancer cell line expressing high level of CD133
      (Capan-1M9), which also expresses high level of Slug. We generated Slug knock
      down subclone (shSlug M9) from this cell line, and compared expression of EMT
      related genes, migration, invasion and gemcitabine resistance between two cell
      lines. Slug knock-down in CD133-positive pancreatic cancer cell line led to the
      reduction of migration and invasion ability. Furthermore, Slug knock-down
      sensitized CD133-positive pancreatic cancer cell line to gemcitabine. These
      results suggest that Slug plays an important role in not only invasion ability
      through EMT but also gemcitabine resistance of CD133-positive pancreatic cancer
      cells. 

PMID- 25997703
TI  - Photodynamic therapy mediates innate immune responses via fibroblast-macrophage
      interactions.
AB  - Antibacterial photodynamic therapy (PDT) has come to attract attention as an
      alternative therapy for drug-resistant bacteria. Recent reports revealed that
      antibacterial PDT induces innate immune response and stimulates abundant cytokine
      secretion as a part of inflammatory responses. However, the underlying mechanism
      how antibacterial PDT interacts with immune cells responsible for cytokine
      secretion has not been well outlined. In this study, we aimed to clarify the
      difference in gene expression and cytokine secretion between combined culture of
      fibroblasts and macrophages and their independent cultures. SCRC-1008, mouse
      fibroblast cell line and J774, mouse macrophage-like cell line were co-cultured
      and PDT treatments with different parameters were carried out. After various
      incubation periods (1-24 h), cells and culture medium were collected, and mRNA
      and protein levels for cytokines were measured using real-time PCR and ELISA,
      respectively. Our results showed that fibroblasts and macrophages interact with
      each other to mediate the immune response. We propose that fibroblasts initially
      respond to PDT by expressing Hspa1b, which regulates the NF-kappaB pathway via
      Tlr2 and Tlr4. Activation of the NF-kappaB pathway then results in an enhanced
      secretion of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) and
      neutrophil chemoattractant MIP-2 and KC from macrophages. 

PMID- 25997704
TI  - Tangential IMRT versus TomoTherapy with and without breath-hold in left-sided
      whole breast irradiation.

PMID- 25997705
TI  - CHOP-like-14 compared to CHOP-like-21 for patients with aggressive lymphoma--a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: R-CHOP-21 has remained the standard chemotherapy for aggressive non
      Hodgkin's lymphoma. It was suggested that decreasing the treatment interval from
      three weeks (CHOP-21) to two weeks (CHOP-14) may improve survival and disease
      control of patients with aggressive lymphoma. PURPOSE: To evaluate the effect of
      CHOP-like-14 (with or without rituximab) compared to standard CHOP-like -21 on
      overall survival (OS), disease control and toxicity of patients with aggressive
      non-Hodgkin lymphoma. METHODS: Systematic review and meta-analysis of RCTs. In
      October 2014 we searched The Cochrane Library, MEDLINE, LILACS, conference
      proceedings, and databases of ongoing trials. Authors were contacted for
      complementary data. The primary outcome was OS. RESULTS: We identified seven
      trials (4073 patients), conducted between the years 1999 and 2008. Trials were at
      low or unclear risk for selection bias, and at low or unclear risk of attrition
      bias. CHOP-like-14 improved OS of patients with aggressive lymphoma compared to
      the same regimen given every 21 days (all trials): HR of death 0.86, 95%
      confidence interval (CI) 0.77-0.97. There was no OS difference between rituximab
      CHOP-like 14 to rituximab-CHOP-like-21 (3 trials): HR 0.93 95% CI 0.78-1.10. The
      rates of progression or death, complete response, treatment-related mortality,
      grade 3-4 infection, and discontinuation were similar between groups. CONCLUSION:
      R-CHOP-21 remains the standard of care for patient with aggressive B-cell
      lymphoma. CHOP-14 can be considered as in case rituximab is omitted.

PMID- 25997706
TI  - Synuclein-gamma promotes migration of MCF7 breast cancer cells by activating
      extracellular-signal regulated kinase pathway and breaking cell-cell junctions.
AB  - Synuclein-gamma (SNCG), a synuclein family member, promotes migration, invasion
      and metastasis of tumor cells; however, the mechanism remains unclear. The
      present study investigated the effect of SNCG on malignant phenotypes of MCF7
      cells using cell proliferation analysis, cell migration assays and wound healing
      assays, and verified its effects on extracellular-signal regulated kinase (Erk)
      activation and epithelial to mesenchymal transition-related markers using western
      blotting. The results indicated that SNCG increased migration (P<0.05) but not
      proliferation (P=0.711) of MCF7 cells. It was also demonstrated that SNCG
      activated the Erk pathway and an inhibitor of Erk signaling significantly
      counteracted SNCG-induced migration. Furthermore, it was shown that SNCG
      downregulated levels of tight junctions-associated factors E-cadherin and ZO-1,
      while inhibiting the Erk pathway did not affect their levels. In conclusion, SNCG
      may promote MCF7 cell migration through activating the Erk pathway and breaking
      cell-cell junctions.

PMID- 25997708
TI  - Looking back on the London Olympics: Independent outcome and hindsight effects in
      decision evaluation.
AB  - Outcome bias and hindsight bias are related, but how exactly? To remedy
      theoretical ambiguity and non-existent directly relevant empirical research, we
      contrast an older idea (Baron & Hershey, 1988, J. Pers. Soc. Psychol., 54, 569)
      that sees outcome bias as partly mediated through hindsight bias with the idea
      that the two biases independently affect decision evaluations. In an Internet
      study of retrospections on the 2012 London Olympics, evaluations of the Games'
      success and its foreseeability had independent effects on evaluations of the
      International Olympic Committee's decision to award the Olympics to London; there
      was no evidence of mediation. Further theoretical discussion emphasizes the need
      to distinguish between a holistic assessment of decisions and a more specific
      assessment of the decision-making process in future outcome bias research. 

PMID- 25997707
TI  - Short-Term Immunogenicity and Safety of an Accelerated Pre-Exposure Prophylaxis
      Regimen With Japanese Encephalitis Vaccine in Combination With a Rabies Vaccine:
      A Phase III, Multicenter, Observer-Blind Study.
AB  - BACKGROUND: The current Japanese encephalitis (JE) vaccination regimen requires
      two doses and 4 weeks to complete, which may not always be feasible for travelers
      on short notice. One of the primary endpoints of this phase III study was to
      demonstrate noninferiority of immune responses to a JE vaccine following an
      accelerated 1-week JE vaccination regimen administered concomitantly with a
      rabies vaccine as compared to a standard 4-week JE regimen alone. In addition,
      the immunogenicity of concomitant administration of JE and rabies vaccines
      following standard regimens was evaluated, as well as the tolerability and safety
      profile of each regimen under study. METHODS: Healthy adults aged 18 to <=65
      years were randomized to regimens with an accelerated or standard schedule:
      JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n =
      56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction
      neutralization test (PRNT50 ) titer of >=1 : 10, measured 28 days after last
      active vaccine (LAV) administration. Solicited reactions were collected 7 days
      after each vaccination; spontaneously reported adverse events (AEs) and serious
      AEs were monitored up to day 57. This paper reports results until day 57.
      RESULTS: Noninferiority of immune responses was established for JE+rabies
      accelerated compared to the JE-standard regimen 28 days after LAV administration.
      Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard
      groups, respectively, achieved PRNT50 titers of >=1 : 10 at 28 days after LAV
      administration. No impact of concomitant rabies vaccination was observed either
      on immune responses or on the safety profile of the JE vaccine. CONCLUSIONS: This
      was the first randomized, controlled trial that demonstrated the strong short
      term immunogenicity of a new, accelerated, 1-week JE-regimen, which was
      noninferior to that of the standard regimen, with a satisfactory tolerability and
      safety profile and no impact of concomitant rabies vaccination. This accelerated
      regimen, if licensed, could potentially be a valid alternative for individuals
      requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis
      on short notice.

PMID- 25997709
TI  - Interleukin-33 Triggers B1 Cell Expansion and Its Release of Monocyte/Macrophage
      Chemoattractants and Growth Factors.
AB  - B1 B lymphocytes are natural IgM-producing cells primarily found in peritoneum
      and mucosal sites. They perform vital functions during the early defence against
      viral and bacterial infections. Murine B1 cells express IL-33 receptor complex on
      activation. IL-33 is a new addition to the IL-1 family with a strong role in Th2
      immunity. B1 cells have been recognized to exacerbate contact sensitivity by
      producing IgM and IL-5 in response to interleukin-33. However, the exact response
      of IL-33/ST2 signalling in B1 cells is not completely understood. In this study,
      we report that murine B1 cells respond directly to IL-33 in a ST2-dependent
      manner. This interaction instigates B1b cell proliferation in a time-dependent
      manner in vivo. Furthermore, it also mediates monocyte/macrophage and granulocyte
      recruitment via B1 cell release of chemokines (MCP-1 and MIP-1 alpha). It was
      noted that upon stimulation, B1b cells additionally release an angiogenic inducer
      vascular endothelial growth factor and granulocyte-monocyte colony-stimulating
      factor (GM-CSF). Our findings suggest that these IL-33-mediated B1 cells might be
      able to play a vital role in the recruitment and growth of monocytes and
      granulocytes.

PMID- 25997714
TI  - Papillary thyroid carcinoma: prognostic significance of cancer presentation.
AB  - BACKGROUND: The objective of this study was to evaluate whether the clinical
      presentation of papillary thyroid carcinoma (PTC) has prognostic significance.
      METHODS: Retrospective evaluation was carried out of sequential, primary
      presentation, >1 cm diameter, PTC cases treated at a single center. PTC cases
      were grouped into 3 groups: (1) incidental detection by imaging, (2) incidental
      detection by physical examination, and (3) detection because of complaints
      related to a thyroid mass. The MACIS (metastasis, age, completeness of resection,
      invasion, and size) system was used to determine cancer prognosis for each group.
      RESULTS: Of the 168 PTC cases, 28 patients (17%) were in group 1, 60 patients
      (36%) were in group 2, and 80 patients (47%) were in group 3. Overall, 53% of
      differentiated thyroid cancers were detected incidentally. The difference in the
      proportion of patients in each MACIS score groups among the 3 clinical
      presentation categories, and for each component of the MACIS score, was not
      statistically significant (P = .36). CONCLUSION: The manner in which PTC
      initially clinically presents has no relationship with cancer prognosis.

PMID- 25997710
TI  - miRNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1.
AB  - The existence of cancer stem cells (CSCs) is considered as a direct reason for
      the failure of clinic treatment in hepatocellular carcinoma (HCC). Growing
      evidences have demonstrated that miRNAs play an important role in regulation of
      stem cell proliferation, differentiation and self-renewal and their aberrances
      cause the formation of CSCs and eventually result in carcinogenesis. We recently
      identified miRNA-148b as one of the miRNAs specifically down-regulated in side
      population (SP) cells of PLC/PRF/5 cell line. However, it remains elusive how
      miRNA-148b regulates CSC properties in HCC. In the present study, we observed
      that overexpression or knockdown of miR-148b through lentiviral transfection
      could affect the proportion of SP cells as well as CSC-related gene expression in
      HCC cell lines. In addition, miR-148b blocking could stimulate cell
      proliferation, enhance chemosensitivity, as well as increase cell metastasis and
      angiogenesis in vitro. More importantly, miR-148b could significantly suppress
      tumorigenicity in vivo. Further studies revealed that Neuropilin-1 (NRP1), a
      transmembrane co-receptor involved in tumour initiation, metastasis and
      angiogenesis, might be the direct target of miRNA-148b. Taking together, our
      findings define that miR-148b might play a critical role in maintenance of SP
      cells with CSC properties by targeting NRP1 in HCC. It is the potential to
      develop a new strategy specifically targeting hepatic CSCs (HCSCs) through
      restoration of miR-148b expression in future therapy. 

PMID- 25997715
TI  - Cervical spine clearance when unable to be cleared clinically: a pooled analysis
      of combined computed tomography and magnetic resonance imaging.
AB  - BACKGROUND: The role of cervical spine magnetic resonance imaging (MRI) in the
      evaluation of clinically unevaluable blunt trauma patients has been called into
      question by several recent studies. METHODS: A PubMed search was performed for
      all studies comparing computed tomography and MRI in the assessment of the
      cervical spine in patients who cannot be evaluated clinically. The radiologic
      findings and clinical outcomes from each study were collated for analysis.
      RESULTS: Data for 1,714 patients were available. All patients had a negative
      computed tomography scan and then underwent an MRI. There were 271 (15.8%)
      patients who had a previously undocumented finding on MRI with the majority
      (98.2%) being a ligamentous injury. Only 5 injuries (1.8%) resulted in surgical
      intervention. CONCLUSIONS: MRI identifies additional injuries; however, the vast
      majority are of minor clinical significance. Routine MRI after a negative
      computed tomography of the cervical spine is not supported by the current
      literature.

PMID- 25997716
TI  - Temporary cervical esophageal exclusion for esophageal leak.

PMID- 25997717
TI  - Integrin beta4 and vinculin contained in exosomes are potential markers for
      progression of prostate cancer associated with taxane-resistance.
AB  - Treatment with taxanes for castration-resistant prostate cancer often leads to
      the development of resistance. It has been recently demonstrated that exosomes
      present in the body fluids contain proteins and RNAs in the cells from which they
      are derived and could serve as a diagnostic marker for various diseases. In the
      present study, we aimed to identify proteins contained in exosomes that could be
      markers for progression and taxane-resistance of prostate cancer. Exosomes were
      isolated by differential centrifugation from the culture medium of taxane
      resistant human prostate cancer PC-3 cells (PC-3R) and their parental PC-3 cells.
      Isolated exosomes were subjected to iTRAQ-based quantitative proteomic analysis.
      Exosomes were also isolated from the culture medium by using anti-CD9 antibody
      conjugated magnetic beads. Protein expression was knocked down by siRNA
      transfection followed by analysis of the silencing effects. Proteomic analysis
      showed that integrin beta4 (ITGB4) and vinculin (VCL) were upregulated in
      exosomes derived from PC-3R cells compared to PC-3 cells. The elevation of ITGB4
      and VCL was confirmed in exosomes captured by anti-CD9 antibody from the culture
      medium of PC-3R cells. Silencing of ITGB4 and VCL expression did not affect
      proliferation and taxane-resistance of PC-3R cells, but ITGB4 knockdown
      attenuated both cell migration and invasion and VCL knockdown reduced invasion.
      Our results suggest that ITGB4 and VCL in exosomes could be useful markers for
      progression of prostate cancer associated with taxane-resistance, providing the
      basis for development of an exosome-based diagnostic system.

PMID- 25997718
TI  - GLUT1 deficiency syndrome and ketogenic diet therapies: missing rare but
      treatable diseases?

PMID- 25997719
TI  - Viral vector delivery of neurotrophic factors for Parkinson's disease therapy.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterised by the
      progressive loss of midbrain dopaminergic neurons, which causes motor
      impairments. Current treatments involve dopamine replacement to address the
      disease symptoms rather than its cause. Factors that promote the survival of
      dopaminergic neurons have been proposed as novel therapies for PD. Several
      dopaminergic neurotrophic factors (NTFs) have been examined for their ability to
      protect and/or restore degenerating dopaminergic neurons, both in animal models
      and in clinical trials. These include glial cell line-derived neurotrophic
      factor, neurturin, cerebral dopamine neurotrophic factor and
      growth/differentiation factor 5. Delivery of these NTFs via injection or infusion
      to the brain raises several practical problems. A new delivery approach for NTFs
      involves the use of recombinant viral vectors to enable long-term expression of
      these factors in brain cells. Vectors used include those based on adenoviruses,
      adeno-associated viruses and lentiviruses. Here we review progress to date on the
      potential of each of these four NTFs as novel therapeutic strategies for PD, as
      well as the challenges that have arisen, from pre-clinical analysis to clinical
      trials. We conclude by discussing recently-developed approaches to optimise the
      delivery of NTF-carrying viral vectors to the brain. 

PMID- 25997720
TI  - [In the Era Of Self-Medication, What Do Pregnant Women Know about Anti
      Inflammatory Drugs?].
AB  - OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated in
      pregnancy because of the many foetal-maternal complications they can induce. Yet,
      NSAIDs can be massively found in family medicine cabinets and they are over-the
      counter drugs for most of them. Because of the actual trend of empowerment and
      public authorities encouraging self-medication, NSAIDs might be used. Our aim was
      to assess pregnant women's knowledge of NSAIDs. STUDY DESIGN: A descriptive
      study, through the distribution of 330 questionnaires to all pregnant women
      consulting at the Teaching hospital of Saint-Etienne, during a week, from
      February 11th, 2014 to 19th, 2014. RESULTS: The answering rate was 96.4%. Around
      46% of pregnant women declared self-medicating. More than 1 in 3 women considered
      NSAIDs without danger starting from their 6th month of pregnancy. Eighty-six
      percent of women recognized ibuprofen as belonging to NSAISs. However, 1 in 2
      women didn't consider Rhinadvil(r) (ibuprofene/pseudoephedrine) as such and
      approximately 40% for Aspegic(r) (lysine acetylsalicylate) and Aspirin(r)
      (acetylsalicylic acid). Danger's perception varied according to the galenic and
      the trade name: 60% of them thought that Rhinadvil(r) was without risks and
      around 1 in 2 women thought the same for Aspirin(r) and Aspegic(r). Eighty-six
      per cent of women recognized ibuprofen as belonging to NSAIDs. However, 1 in 2
      women didn't consider Rhinadvil(r) as such and approximately 40% for Apegic(r)
      and Aspirin(r). CONCLUSION: Pregnant women's knowledge of NSAIDs is not
      satisfactory. They are not aware of their danger and do not know how to recognize
      them. Yet, self-medication is rising and its accessibility is made easier. A work
      on prevention and information is therefore essential.

PMID- 25997721
TI  - [Orphan Drugs: Underrated Opportunities for The Developers in Europe].
AB  - In Europe, rules relating to the designation and the protection of orphan drug
      are derived from regulation (EC) 141/2000 of the European Parliament and Council
      of 16 December 1999, specified by the implementing Regulation (EC) 847/2000.
      According to these regulations, obtaining the status of orphan drugs implies, in
      particular, to demonstrate the absence of any satisfying alternative treatment,
      or, by default, the significant benefit offered by the concerned drug. In the
      same sense, medicinal product similar to an original orphan medicinal product but
      safer, more effective or otherwise clinically superior, will benefit from a
      derogation to the rules on the 10 years market exclusivity usually provided for
      these products. This article analyses the concept of significant benefit, namely,
      the clinically relevant advantage or a major contribution to patient care, in
      particular in the case of similar drugs, as well as the elements to be provided
      by the sponsor in order to justify this benefit, and the options under which,
      where there are few or a lack of clinical data on a concerned orphan medicinal
      products, the demonstration of the significant benefit can rely on assumptions. 

PMID- 25997722
TI  - Hydrogen Suppresses Hypoxia/Reoxygenation-Induced Cell Death in Hippocampal
      Neurons Through Reducing Oxidative Stress.
AB  - BACKGROUND & AIMS: Deep hypothermic circulatory arrest (DHCA) is a cerebral
      protection technique that has been used in the operations involving the aortic
      arch and brain aneurysm for decades. We previous showed that DHCA treated rats
      developed a significant oxidative stress and apoptosis in neurons. We here intend
      to investigate the protective the effect of hydrogen against oxidative stress
      induced cell injury and the involved mechanisms using an in vitro experimental
      model of hypoxia/reoxygenation (H/R) on HT-22 cells. METHODS: The model of H/R
      was established using an airtight culture container and the anaeropack.
      Measurement of mitochondrial membrane potential (MMP) and reactive oxygen species
      (ROS) production was used H2DCFDA and JC-1 staining. Western blot was used for
      the quantification of Akt, p-Akt, Bcl-2, Bax and cleaved caspase-3 proteins. The
      microRNA (miRNA) profile in hippocampal neurons from rat model of DHCA was
      determined by miRNA deep sequencing. RESULTS: The elevation of ROS and reduction
      of MMP were significantly induced by the treatment with hypoxia for 18 h followed
      by reoxygenation for 6 h. Hydrogen treatment significantly reduced H/R-caused
      cell death. The levels of p-Akt (Ser 473) and Bcl-2 were significantly increased
      while Bax and cleaved caspase-3 were decreased by hydrogen treatment on the model
      of H/R. The expression of miR-200 family was significantly elevated in model of
      DHCA and H/R. Hydrogen administration inhibited the H/R-induced expression of miR
      200 family in HT-22 cells. In addition, inhibition of miR-200 family suppressed
      H/R-caused cell death through reducing ROS production. CONCLUSIONS: These results
      suggest that H/R causes oxidative stress-induced cell death and that the hydrogen
      protects against H/R-induced cell death in HT22 cells, in part, due to reducing
      expression of miR-200 family.

PMID- 25997723
TI  - Advances in nicotine research in Addiction Biology.
AB  - The aim of Addiction Biology is to advance our understanding of the action of
      drugs of abuse and addictive processes via the publication of high-impact
      clinical and pre-clinical findings resulting from behavioral, molecular, genetic,
      biochemical, neurobiological and pharmacological research. As of 2013, Addiction
      Biology is ranked number 1 in the category of Substance Abuse journals (SCI).
      Occasionally, Addiction Biology likes to highlight via review important findings
      focused on a particular topic and recently published in the journal. The current
      review summarizes a number of key publications from Addiction Biology that have
      contributed to the current knowledge of nicotine research, comprising a wide
      spectrum of approaches, both clinical and pre-clinical, at the cellular,
      molecular, systems and behavioral levels. A number of findings from human studies
      have identified, using imaging techniques, alterations in common brain circuits,
      as well as morphological and network activity changes, associated with tobacco
      use. Furthermore, both clinical and pre-clinical studies have characterized a
      number of mechanistic targets critical to understanding the effects of nicotine
      and tobacco addiction. Together, these findings will undoubtedly drive future
      studies examining the dramatic impact of tobacco use and the development of
      treatments to counter nicotine dependence. 

PMID- 25997724
TI  - Gestural Control in the English Past-Tense Suffix: An Articulatory Study Using
      Real-Time MRI.
AB  - The English past tense allomorph following a coronal stop (e.g., /balphanded/)
      includes a vocoid that has traditionally been transcribed as a schwa or as a
      barred i. Previous evidence has suggested that this entity does not involve a
      specific articulatory gesture of any kind. Rather, its presence may simply result
      from temporal coordination of the two temporally adjacent coronal gestures, while
      the interval between those two gestures remains voiced and is acoustically
      reminiscent of a schwa. The acoustic and articulatory characteristics of this
      vocoid are reexamined in this work using real-time MRI with synchronized audio
      which affords complete midsagittal views of the vocal tract. A novel statistical
      analysis is developed to address the issue of articulatory targetlessness based
      on previous models that predict articulatory action from segmental context.
      Results reinforce the idea that this vocoid is different, both acoustically and
      articulatorily, than lexical schwa, but its targetless nature is not supported.
      Data suggest that an articulatory target does exist, especially in the pharynx
      where it is revealed by the new data acquisition methodology. Moreover,
      substantial articulatory differences are observed between subjects, which
      highlights both the difficulty in characterizing this entity previously, and the
      need for further study with additional subjects.

PMID- 25997725
TI  - Body dysmorphic disorder in dermatology: beware of diagnostic overlabelling.

PMID- 25997727
TI  - A biomechanical model of pendelluft induced lung injury.
AB  - Lung ventilation using high frequency oscillatory techniques have been documented
      to attain adequate gas exchange through various gas transport mechanisms. Among
      them, the pendelluft flow is considered one of the most crucial mechanisms. In
      this work, we computationally investigate the induction of abnormal mechanical
      stresses and a regionally trapped volume of gas due to pendelluft flow. Large
      eddy simulation was used to model the turbulence in an upper tracheobronchial
      lung geometry that was derived from CT scans. The pendelluft flow was captured by
      modeling physiological boundary conditions at the truncated level of the lung
      model that is sensitive to the coupled resistance and compliance of individual
      patients. The flow-volume and volume-pressure loops are characterized by
      irregular shapes and suggest abnormal regional lung ventilation. Incomplete loops
      were observed indicating gas trapping in these regions signifying a potential for
      local injury due to incomplete ventilation from a residual volume build-up at the
      end of the expiration phase. In addition, the gas exchange between units was
      observed to create a velocity gradient causing a region of high wall shear stress
      surrounding the carina ridges. The recurrence of the pendelluft flow could cause
      a rupture to the lung epithelium layer. The trapped gas and wall shear stress
      were observed to amplify with increasing compliance asymmetry and ventilator
      operating frequency. In general, despite the significant contribution of the
      pendelluft flow to the gas exchange augmentation there exists significant risks
      of localized lung injury, phenomena we describe as pendelluft induced lung injury
      or PILI. 

PMID- 25997726
TI  - In-vivo hip arthrokinematics during supine clinical exams: Application to the
      study of femoroacetabular impingement.
AB  - Visualization of hip articulation relative to the underlying anatomy (i.e.,
      arthrokinematics) is required to understand hip dysfunction in femoroacetabular
      (FAI) patients. In this exploratory study, we quantified in-vivo arthrokinematics
      of a small cohort of asymptomatic volunteers and three symptomatic patients with
      varying FAI deformities during the passive impingement, FABER, and rotational
      profile exams using dual fluoroscopy and model-based tracking. Joint angles,
      joint translations, and relative pelvic angles were calculated. Compared to the
      95% confidence interval of the asymptomatic cohort, FAI patients appeared to have
      decreased adduction and internal rotation during the impingement exam and greater
      flexion and less abduction/external rotation in the FABER exam. During the
      rotational profile, only the FAI patient with the most severe deformities
      demonstrated considerable rotation deficits. In all participants, contact between
      the labrum and femoral head/neck limited motion during the impingement exam, but
      not the rotational profile. Substantial pelvic motion was measured during the
      impingement exam and FABER test in all participants. Femoral translation along
      any given anatomical direction ranged between 0.69 and 4.1mm. These results
      suggest that hip articulation during clinical exams is complex in asymptomatic
      hips and hips with FAI, incorporating pelvic motion and femur translation. Range
      of motion appears to be governed by femur-labrum contact and other soft tissue
      constraints, suggesting that current computer simulations that rely on direct
      bone contact to predict impingement may be unrealistic. Additional research is
      necessary to confirm these preliminary results. Still, dual fluoroscopy data may
      serve to validate existing software platforms or create new programs that better
      represent hip arthrokinematics. 

PMID- 25997728
TI  - Current radiosynthesis strategies for 5-HT2A receptor PET tracers.
AB  - Serotonin 2A receptors have been implicated in various psychophysiological
      functions and disorders such as depression, Alzheimer's disease, or
      schizophrenia. Therefore, neuroimaging of this specific receptor is of
      significant clinical interest, and it is not surprising that many attempts have
      been made to develop a suitable 5-HT2A R positron emission tomography-tracer. In
      this review, we give an overview on the precursor, reference compound synthesis,
      and the preparation of promising 5-HT2A R radiopharmaceuticals applied in
      positron emission tomography. We also highlight possible learning outcomes that
      can be made from these tracer development processes. 

PMID- 25997729
TI  - Digital voice recorders - A conceptual intervention to facilitate contemporaneous
      record keeping in midwifery practice.
AB  - BACKGROUND: The first responder, faced with any obstetric incident, frequently
      finds themselves within a dichotomy of multi-tasking activities. One challenge
      for the midwife, is to keep accurate and contemporaneous medical records, whilst
      simultaneously providing immediate clinical care. AIM: This paper aims to propose
      an innovative conceptualisation and a practical solution for maternity services,
      which strive to uphold best practice in creating contemporaneous and accurate
      medical records. The feasibility of introducing the use of voice recorders within
      maternity services will be explored, and offered as a mechanism to facilitate
      record keeping and simultaneous clinical care. METHODS: A synthesised narrative
      review of the literature is conducted. This review academically tests the
      conceptual hypothesis that the implementation of voice recorders within maternity
      services may augment the midwife's ability to generate contemporaneous medical
      records. A background literature review will also explore the key drivers for
      this particular innovation, and the challenges facing healthcare leaders in
      service improvement. FINDINGS: This paper builds upon previous suggestions that
      digital voice recorders may be an effective solution to enhance overall obstetric
      outcomes, and focuses upon conceptual processes for implementation. CONCLUSIONS:
      This paper offers the principal conclusion that the integration of voice
      recorders into midwifery practice for the purpose of supporting contemporaneous
      record keeping may be feasible within the current healthcare climate.

PMID- 25997730
TI  - Empathy and spiritual care in midwifery practice: Contributing to women's
      enhanced birth experiences.
AB  - BACKGROUND: Research has identified empathy as a crucial ingredient in effective
      practice for health professionals, including midwifery. Equally, the role of
      spirituality has been recognised as enhancing the quality of the birth experience
      through the care, compassion and presence of the midwife. Yet literature
      discussing birthing women's lived experiences of caregiver empathy and spiritual
      care appears uncommon. AIM: The aim of this article is to highlight women's
      stories about midwives' empathy and spiritual care or lack thereof during birth,
      in order to contribute to the promotion of more empathic, spiritually aware
      midwifery practice. METHODS: Ten interviews and seven focus groups were conducted
      with forty-eight women, including mothers, midwives and staff from a women's
      service. A secondary analysis of the data was conducted examining women's
      descriptions and reflections on midwives' levels of empathy and spiritual care.
      FINDINGS: When midwives' empathy and spiritual care were evident, women's birth
      experiences appeared enhanced, providing a solid foundation for confident
      mothering. Conversely, participants appeared to link a lack of caregiver empathy,
      compassion or spiritual care with more enduring consequences, birth trauma and
      difficulty bonding with their babies. CONCLUSION: Midwives' empathy and spiritual
      care can play a key role in creating positive birth and mothering experiences.
      More research into the role of empathy and spiritual care in enhancing midwifery
      practice in all birth settings is recommended, as is the increased embeddedness
      of empathic regard and the notion of 'birth as sacred' into midwifery curricula.

PMID- 25997731
TI  - Reasons for women's non-participation in follow-up screening after gestational
      diabetes.
AB  - BACKGROUND: Due to the increased risk of type 2 diabetes, follow-up screening
      after birth is recommended to women with previous gestational diabetes. Low
      participation in such screening has been shown to delay detection of diabetes
      with potentially serious consequences for the women's future health. The women's
      experiences of treatment and care during their pregnancies may affect
      participation. AIM: This study aimed at understanding the women's experiences
      with treatment and care during pregnancy and to understand how these experiences
      influence participation in follow-up screening. METHODS: A qualitative study was
      undertaken drawing on a phenomenological methodology. Seven women treated for
      gestational diabetes at a university hospital in the North Denmark Region
      participated in interviews. FINDINGS: The women experienced lack of continuity in
      care between hospital departments and health sectors. We identified the following
      causes for low participation in follow-up screening: poor coordination, little
      elaboration of information, a lack of clear coordination of responsibility for
      follow-up screening among health care professionals and absence of focus and
      inclusion of their individual needs and preferences. CONCLUSION: The women wished
      to be reminded of screening to increase their sense of safety. The women's
      experiences seem to reflect a lack of patient-centeredness during the pregnancy,
      which may be remedied by increasing the focus on the women's need for improved
      continuity in treatment and care. Participation in follow-up screening after
      gestational diabetes may be increased by sending reminders to the women. Raised
      awareness of the women's individual needs and preferences for treatment and care
      offers potential for improvement.

PMID- 25997732
TI  - Computer-Aided Diagnosis of Depression Using EEG Signals.
AB  - The complex, nonlinear and non-stationary electroencephalogram (EEG) signals are
      very tedious to interpret visually and highly difficult to extract the
      significant features from them. The linear and nonlinear methods are effective in
      identifying the changes in EEG signals for the detection of depression. Linear
      methods do not exhibit the complex dynamical variations in the EEG signals.
      Hence, chaos theory and nonlinear dynamic methods are widely used in extracting
      the EEG signal features for computer-aided diagnosis (CAD) of depression. Hence,
      this article presents the recent efforts on CAD of depression using EEG signals
      with a focus on using nonlinear methods. Such a CAD system is simple to use and
      may be used by the clinicians as a tool to confirm their diagnosis. It should be
      of a particular value to enable the early detection of depression.

PMID- 25997733
TI  - Prognostic Significance of the Number of Metastatic pN2 Lymph Nodes in Stage IIIA
      N2 Non-Small-Cell Lung Cancer After Curative Resection.
AB  - Stage IIIA-N2 non-small cell lung cancer (NSCLC) shows prognostic heterogeneity.
      We investigated the prognostic relevance of the number of metastatic pN2 nodes in
      patients with IIIA-N2 NSCLC. The criteria for the number of pN2 used in this
      study were significantly associated with the survival outcomes after surgery and
      may improve the accuracy of prognostic prediction in this subgroup of patients.
      INTRODUCTION: There have been controversies regarding the prognostic relevance of
      the number of positive N2 nodes in pathologic stage IIIA-N2 non-small-cell lung
      cancer (NSCLC). We examine prognosis of patients with pathologic stage IIIA-N2
      with classifying the number of positive N2 nodes into subgroups. METHODS: From
      January 1997 to December 2004, 250 patients were diagnosed with pathologic stage
      IIIA-N2 disease. All patients underwent mediastinal lymph node dissection. After
      excluding 44 patients with preoperative chemotherapy, incomplete resection, and
      postsurgical mortality, 206 patients were included in the analysis. Patients were
      classified according to the number of positive N2 lymph nodes (N2a: 1 [n = 83],
      N2b: 2-4 [n = 82], N2c: >= 5 [n = 41]), and its correlation with survival
      outcomes were investigated. RESULTS: With a median follow-up of 96.3 months, 5
      year disease-free survival (DFS) was 27.2% (95% confidence interval [CI], 21.6
      33.7), and 5-year overall survival (OS) was 37.7% (95% CI, 31.5-44.7) in all
      patients. The number of metastatic N2 lymph nodes was associated with DFS (P <
      .001) and OS (P = .01). In the N2a, N2b, and N2c groups, 5-year DFS rates were
      38%, 24%, and 5%, respectively, and 5-year OS rates were 47%, 35%, and 24%,
      respectively. In a multivariate analysis, the number of metastatic N2 lymph nodes
      was an independent prognostic factor for DFS and OS. CONCLUSION: Stratification
      of patients according to the number of metastatic N2 lymph nodes may improve the
      accuracy of prognostic prediction among patients with curatively resected stage
      IIIA-N2 NSCLC.

PMID- 25997734
TI  - Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1(-/-) Mice.
AB  - Attention deficit/hyperactivity disorder (ADHD) is one of the most common
      neurodevelopmental disorders, affecting approximately 5% of children. However,
      the neural mechanisms underlying its development and treatment are yet to be
      elucidated. In this study, we report that an ADHD mouse model, which harbors a
      deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus
      (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs
      to the thalamus. A moderate level of astrocytosis was displayed in other regions
      of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but
      not in other brain regions, such as the caudate putamen, basolateral amygdala,
      and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was
      detected in both in adult (2-3 months old) and juvenile (4 weeks old) Git1(-/-)
      mice, suggesting a developmental origin. Astrocytes play an active role in the
      developing synaptic circuit; therefore, we performed an immunohistochemical
      analysis of synaptic markers. We detected increased and decreased levels of GABA
      and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis
      may alter synaptic transmission in the basal ganglia. Intriguingly, increased
      GABA expression colocalized with the astrocyte marker, GFAP, indicative of an
      astrocytic origin. Collectively, these results suggest that defects in basal
      ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are
      neural correlates for the ADHD-associated behavioral manifestations in Git1(-/-)
      mice.

PMID- 25997735
TI  - Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via
      PI3K/Akt Activation and Bcl-2 Expression.
AB  - Olfactory stimulation activates multiple signaling cascades in order to mediate
      activity-driven changes in gene expression that promote neuronal survival. To
      date, the mechanisms involved in activity-dependent olfactory neuronal survival
      have yet to be fully elucidated. In the current study, we observed that olfactory
      sensory stimulation, which caused neuronal activation, promoted activation of the
      phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and the expression of Bcl-2,
      which were responsible for olfactory receptor neuron (ORN) survival. We
      demonstrated that Bcl-2 expression increased after odorant stimulation both in
      vivo and in vitro. We also showed that odorant stimulation activated Akt, and
      that Akt activation was completely blocked by incubation with both a PI3K
      inhibitor (LY294002) and Akt1 small interfering RNA. Moreover, blocking the
      PI3K/Akt pathway diminished the odorant-induced Bcl-2 expression, as well as the
      effects on odorant-induced ORN survival. A temporal difference was noted between
      the activation of Akt1 and the expression of Bcl-2 following odorant stimulation.
      Blocking the PI3K/Akt pathway did not affect ORN survival in the time range prior
      to the increase in Bcl-2 expression, implying that these two events, activation
      of the PI3K pathway and Bcl-2 induction, were tightly connected to promote post
      translational ORN survival. Collectively, our results indicated that olfactory
      activity activated PI3K/Akt, induced Bcl-2, and promoted long term ORN survival
      as a result. 

PMID- 25997736
TI  - Suppression of ASKbeta (AtSK32), a Clade III Arabidopsis GSK3, Leads to the
      Pollen Defect during Late Pollen Development.
AB  - Arabidopsis Shaggy-like protein kinases (ASKs) are Arabidopsis thaliana homologs
      of glycogen synthase kinase 3/SHAGGY-like kinases (GSK3/SGG), which are comprised
      of 10 genes with diverse functions. To dissect the function of ASKbeta (AtSK32),
      ASKbeta antisense transgenic plants were generated, revealing the effects of
      ASKbeta down-regulation in Arabidopsis. Suppression of ASKbeta expression
      specifically interfered with pollen development and fertility without altering
      the plants' vegetative phenotypes, which differed from the phenotypes reported
      for Arabidopsis plants defective in other ASK members. The strength of these
      phenotypes showed an inverse correlation with the expression levels of ASKbeta
      and its co-expressed genes. In the aborted pollen of ASKbeta antisense plants,
      loss of nuclei and shrunken cytoplasm began to appear at the bicellular stage of
      microgametogenesis. The in silico analysis of promoter and the expression
      characteristics implicate ASKbeta is associated with the expression of genes
      known to be involved in sperm cell differentiation. We speculate that ASKbeta
      indirectly affects the transcription of its co-expressed genes through the
      phosphorylation of its target proteins during late pollen development. 

PMID- 25997738
TI  - Proper Activity of Histone H3 Lysine 4 (H3K4) Methyltransferase Is Required for
      Morphogenesis during Zebrafish Cardiogenesis.
AB  - While increasing evidence indicates the important function of histone methylation
      during development, how this process influences cardiac development in
      vertebrates has not been explored. Here, we elucidate the functions of two
      histone H3 lysine 4 (H3K4) methylation enzymes, SMYD3 and SETD7, during zebrafish
      heart morphogenesis using gene expression profiling by whole mount in situ
      hybridization and antisense morpholino oligonucleotide (MO)-based gene knockdown.
      We find both smyd3 and setd7 are highly expressed within developing zebrafish
      heart and knock-down of these genes led to severe defects in cardiac
      morphogenesis without altering the expressions pattern of heart markers,
      including cmlc2, vmhc, and amhc. Furthermore, double knock-down by coinjection of
      smyd3 and setd7 MOs caused the synergistic defects in heart development. As
      similar to knock-down effect, overexpression of these genes also caused the heart
      morphogenesis defect in zebrafish. These results indicate that histone modifying
      enzymes, SMYD3 and SETD7, appear to function synergistically during heart
      development and their proper functioning is essential for normal heart
      morphogenesis during development. 

PMID- 25997737
TI  - Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies.
AB  - Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have
      been emerging as bioactive lipids since ceramide was reported to play a role in
      human leukemia HL-60 cell differentiation and death. Recently, it is well-known
      that ceramide acts as an inducer of cell death, that sphingomyelin works as a
      regulator for microdomain function of the cell membrane, and that sphingosine-1
      phosphate plays a role in cell survival/proliferation. The lipids are metabolized
      by the specific enzymes, and each metabolite could be again returned to the
      original form by the reverse action of the different enzyme or after a long
      journey of many metabolizing/synthesizing pathways. In addition, the metabolites
      may serve as reciprocal bio-modulators like the rheostat between ceramide and
      sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the
      subcellular localization and the downstream signal in a specific subcellular
      organelle should be clarified to understand the pathobiological significance of
      sphingolipids when extracellular stimulation induces a diverse of cell functions
      such as cell death, proliferation and migration. In this review, we focus on how
      sphingolipids and their metabolizing enzymes cooperatively exert their function
      in proliferation, migration, autophagy and death of hematopoetic cells, and
      discuss the way developing a novel therapeutic device through the regulation of
      sphingolipids for effectively inhibiting cell proliferation and inducing cell
      death in hematological malignancies such as leukemia, malignant lymphoma and
      multiple myeloma. 

PMID- 25997739
TI  - Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in
      Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic
      Activity.
AB  - Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins
      although their functional difference in lipoprotein metabolism is still unclear.
      To compare anti-atherogenic properties between apoA-I and apoA-4, we
      characterized both proteins in lipid-free and lipid-bound state. In lipid-free
      state, apoA4 showed two distinct bands, around 78 and 67 A on native gel
      electrophoresis, while apoA-I showed scattered band pattern less than 71 A. In
      reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 A and
      113 A, while apoA-I-rHDL showed almost single band around 98 A size. Lipid-free
      apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid
      free state, BS3-crosslinking revealed that apoA-4 showed less multimerization
      tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1),
      apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content
      (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation.
      Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability
      than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid
      free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA
      4 showed less anti-atherogenic activity with more sensitivity to glycation. In
      conclusion, apoA-4 showed inferior physiological functions in lipid-bound state,
      compared with those of apoA-I, to induce more pro-atherosclerotic properties. 

PMID- 25997741
TI  - Dinuclear versus mononuclear pathways in zinc mediated nucleophilic addition: a
      combined experimental and DFT study.
AB  - Employing the oxidative coupling of phenylacetylene with benzaldehyde as a model
      reaction, a density functional theory (DFT) study combined with extended X-ray
      absorption fine structure (EXAFS) experiment was carried out to reveal the
      difference between dinuclear and mononuclear zinc mediated nucleophilic addition.
      Newly reported DFT method M11-L computed results suggest that the mononuclear
      zinc mediated pathway, in which nucleophilic addition occurs via a four-membered
      ring transition state, is unfavourable both thermodynamically and kinetically.
      The dinuclear zinc mechanism, which appropriately explains the experimental
      observations, involves a six-membered ring transition state for nucleophilic
      addition. Subsequent in situ EXAFS experiment confirmed the existence of
      dinuclear zinc active species. Moreover, frontier molecular orbital (FMO)
      analysis and distortion-interaction energy analysis along the whole reaction
      pathways have provided interpretations for the advantage of dinuclear zinc
      mediated nucleophilic addition. Consequently, we believe this dinuclear zinc
      pathway will open up a general consideration of the dinuclear zinc mechanism for
      nucleophilic additions. 

PMID- 25997740
TI  - miR-335 Targets SIAH2 and Confers Sensitivity to Anti-Cancer Drugs by Increasing
      the Expression of HDAC3.
AB  - We previously reported the role of histone deacetylase 3 (HDAC3) in response to
      anti-cancer drugs. The decreased expression of HDAC3 in anti-cancer drug
      resistant cancer cell line is responsible for the resistance to anti-cancer
      drugs. In this study, we investigated molecular mechanisms associated with
      regulation of HDAC3 expression. MG132, an inhibitor of proteasomal degradation,
      induced the expression of HDAC3 in various anti-cancer drug-resistant cancer cell
      lines. Ubiquitination of HDAC3 was observed in various anti-cancer drug-resistant
      cancer cell lines. HDAC3 showed an interaction with SIAH2, an ubiquitin E3
      ligase, that has increased expression in various anti-cancer drug-resistant
      cancer cell lines. miRNA array analysis showed the decreased expression of miR
      335 in these cells. Targetscan analysis predicted the binding of miR-335 to the
      3'-UTR of SIAH2. miR-335-mediated increased sensitivity to anti-cancer drugs was
      associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted
      apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug
      resistant cancer cell lines. miR-335 negatively regulated the invasion,
      migration, and growth rate of cancer cells. The mouse xenograft model showed that
      miR-335 negatively regulated the tumorigenic potential of cancer cells. The down
      regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of
      the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to
      anti-cancer drugs. 

PMID- 25997743
TI  - 35-Year Follow-Up of a Case of Ring Chromosome 2: Array-CGH Analysis and
      Literature Review of the Ring Syndrome.
AB  - Cote et al. [1981] suggested that ring chromosomes with or without deletions
      share a common pattern of phenotypic anomalies, regardless of which chromosome is
      involved. The phenotype of this 'general ring syndrome' consists of growth
      failure without malformations, few or no minor anomalies, and mild to moderate
      mental retardation. We reconsidered the ring chromosome 2 case previously
      published by Cote et al. [1981], and we characterized it by array CGH,
      polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal
      deletion (q37.3qter) of maternal origin of the long arm of the ring chromosome 2
      was detected and confirmed by all the above-mentioned methods. Ring chromosome 2
      cases are exceedingly rare. Only 18 cases, including the present one, have been
      published so far, and our patient is the longest reported survivor, with a 35
      year follow-up, and the third case characterized by array-CGH analysis.

PMID- 25997742
TI  - Altered lysosomal positioning affects lysosomal functions in a cellular model of
      Huntington's disease.
AB  - Huntington's disease (HD) is a hereditary and devastating neurodegenerative
      disorder caused by a mutation in the huntingtin protein. Understanding the
      functions of normal and mutant huntingtin protein is the key to revealing the
      pathogenesis of HD and developing therapeutic targets. Huntingtin plays an
      important role in vesicular and organelle trafficking. Lysosomes are dynamic
      organelles that integrate several degradative pathways and regulate the activity
      of mammalian target of rapamycin complex 1 (mTORC1). In the present study, we
      found that the perinuclear accumulation of lysosomes was increased in a cellular
      model of HD derived from HD knock-in mice and primary fibroblasts from an HD
      patient. This perinuclear lysosomal accumulation could be reversed when normal
      huntingtin was overexpressed in HD cells. When we further investigated the
      functional significance of the increased perinuclear lysosomal accumulation in HD
      cells, we demonstrated that basal mTORC1 activity was increased in HD cells. In
      addition, autophagic influx was also increased in HD cells in response to serum
      deprivation, which leads to premature fusion of lysosomes with autophagosomes.
      Taken together, our data suggest that the increased perinuclear accumulation of
      lysosomes may play an important role in HD pathogenesis by altering lysosomal
      dependent functions. 

PMID- 25997744
TI  - Uygur medicine Xipayi Kui Jie'an affects gene expression profiles in intestinal
      tissue lesions in a rat model of ulcerative colitis.
AB  - BACKGROUND: The aim of this study was to investigate the mechanisms underlying
      the therapeutic effect of Uygur medicine KJA on UC in a rat model. METHODS: UC
      was induced in Wistar rats by application of 2, 4-dinitrochlorobenzene and acetic
      acid and were then treated with three different doses of KJA, and normal saline
      as control. After treatment for 20 days, the gene expression profile of colonic
      tissue was analyzed by microarray and verified by quantitative real-time RT-PCR.
      RESULTS: Animals treated with the three different doses of KJA were compared with
      normal saline controls, wherein microarray analysis identified 1991, 2163, and
      1677 differentially expressed genes respectively, of which 444 genes were raised
      and 670 genes were decrease spliced together in the three doses tested. The KEGG
      pathway analyses found commonly raised genes related to several different
      biological functions. Interesting genes included TRL2, IL-1beta, TGF-beta1, and
      NF-kappaB were confirmed by quantitative PCR. CONCLUSIONS: The therapeutic effect
      of KJA on UC is likely explained by specific effects on the expression of genes,
      which are the effector molecules known to be involved in the development of UC.
      Further studies on differentially expressed genes will help explain the mechanism
      of action of Uygur medicine KJA.

PMID- 25997745
TI  - TANK-binding kinase 1 (TBK1) modulates inflammatory hyperalgesia by regulating
      MAP kinases and NF-kappaB dependent genes.
AB  - BACKGROUND: TANK-binding kinase (TBK1) is a non-canonical IkappaB kinase (IKK)
      involved in the regulation of type I interferons and of NF-kappaB signal
      transduction. It is activated by viral infections and inflammatory mediators and
      has therefore been associated with viral diseases, obesity, and rheumatoid
      arthritis. Its role in pain has not been investigated so far. Due to the
      important roles of NF-kappaB, classical IkappaB Kinases and the IKK-related
      kinase, IKKepsilon, in inflammatory nociception, we hypothesized that TBK1, which
      is suggested to form a complex with IKKepsilon under certain conditions, might
      also alter the inflammatory nociceptive response. METHODS: We investigated TBK1
      expression and regulation in "pain-relevant" tissues of C57BL/6 mice by
      immunofluorescence, quantitative PCR, and Western blot analysis. Furthermore,
      nociceptive responses and the underlying signal transduction pathways were
      assessed using TBK1(-/-) mice in two models of inflammatory nociception. RESULTS:
      Our data show that TBK1 is expressed and regulated in the spinal cord after
      peripheral nociceptive stimulation and that a deletion of TBK1 alleviated the
      inflammatory hyperalgesia in mice while motor function and acute nociception were
      not altered. TBK1-mediated effects are at least partially mediated by regulation
      of NF-kappaB dependent COX-2 induction but also by alteration of expression of c
      fos via modulation of MAP kinases as shown in the spinal cord of mice and in cell
      culture experiments. CONCLUSION: We suggest that TBK1 exerts pronociceptive
      effects in inflammatory nociception which are due to both modulation of NF-kappaB
      dependent genes and regulation of MAPKs and c-fos. Inhibition of TBK1 might
      therefore constitute a novel effective tool for analgesic therapy.

PMID- 25997747
TI  - Protein and polysaccharide content of tightly and loosely bound extracellular
      polymeric substances and the development of a granular activated sludge floc.
AB  - A full-scale (FS) activated sludge system treating wastewater from a meat
      rendering plant with a long history of sludge management problems (pin-point
      flocs; >80% of floc <50 MUm diameter; poor settling) was the focus of a study
      that entailed characterization of floc properties. This was coupled with parallel
      well-controlled lab-scale (LS) sequencing batch reactors (SBRs) treating the same
      wastewater and operated continuously over 1.5 years. Distinct differences in the
      proportion of proteins and polysaccharides associated with extracellular
      polymeric substances (EPS) were observed when comparing the properties of flocs
      from the FS and the LB systems. Further differences in the proportion of tightly
      bound (TB) and loosely bound (LB) fractions of EPS were also observed for flocs
      derived from conditions where differences in settling and dewatering properties
      of flocs occurred (i.e. FS and LS systems). FS flocs contained higher levels of
      EPS along with a higher proportion of LB than TB EPS, and possessing
      characteristics associated with non-filamentous bulking (SVI >150 mL/g). Floc
      formed in the LS system, following inoculation from sludge taken from the FS
      system, was markedly larger in size (>70% of floc >300 MUm diameter), spherical
      in shape, compact and firm, and appeared to be granular in form. Flocs formed in
      the LS system, when an anoxic phase was introduced into the react stage of the
      SBR cycle, were found to be more hydrophobic and contained more TB and less
      loosely bound (LB) EPS when compared to the FS floc. TB-EPS contained a greater
      amount of protein, whereas the polysaccharide content of LB-EPS was larger.
      Protein was predominantly localized in the core region of granular flocs where
      cells were compactly packed. When assessing the operating conditions of the FS
      and LS systems parameters that appear to impact the floc properties and the
      transition to a granular form include dissolved oxygen (DO) concentration and
      food to microorganism (F/M) ratio.

PMID- 25997748
TI  - New insights into the primary phototransformation of acetaminophen by UV/H2O2:
      photo-Fries rearrangement versus hydroxyl radical induced hydroxylation.
AB  - The phototransformation of acetaminophen (APAP) by UV/H2O2 in deionized water and
      sewage treatment plant (STP) effluents was studied systematically by a
      combination of analysis of the reaction intermediates and kinetic study. 1-(2
      amino-5-hydroxyphenyl)ethanone (P1) and the reported N-(3,4
      dihydroxyphenyl)acetamide (P2) were identified as the main transformation
      intermediates during the transformation of APAP by UV/H2O2. There was no
      influence of OH on the formation kinetics of P1, while its decay was promoted.
      The formation and decay kinetics of P2 were accelerated by increases in the
      concentration of OH. The second-order rate constants for the reaction of OH with
      APAP, P1, and P2 were 3.9 * 10(9), 8.1 * 10(9), and 4.7 * 10(9) M(-1) s(-1),
      respectively. The kinetic study indicated that the main transformation of APAP
      also included transformation to 1,4-hydroquinone, although the accumulated
      concentration of 1,4-hydroquinone was quite low. The presence of anions (Cl(-),
      HCO3(-)/CO3(2-) NO2(-)/NO3(-)), humic acid, commercial drug components or
      adjuvants, and dissolved organic matters in STP effluents not only changed the
      transformation kinetics of APAP, but also altered the distribution of the
      intermediates. The kinetics and pathway of APAP transformation in STP effluent
      were markedly different from those in deionized water.

PMID- 25997746
TI  - Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous
      failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre
      randomised trial.
AB  - INTRODUCTION: For patients with rheumatoid arthritis (RA) whose treatment with a
      tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment
      options are available. Often, another TNFi or a biological with another mode of
      action is prescribed. The objective of this study was to compare the
      effectiveness and cost-effectiveness of three biologic treatments with different
      modes of action in patients with RA whose TNFi therapy is failing. METHODS: We
      conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients
      with active RA despite previous TNFi treatment were randomised to receive
      abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity
      Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire
      Disability Index and 36-item Short Form Health Survey scores) were analysed using
      linear mixed models. Cost-effectiveness was analysed on the basis of incremental
      net monetary benefit, which was based on quality-adjusted life-years (calculated
      using EQ-5D scores), and all medication expenditures consumed in 1 year. All
      analyses were also corrected for possible confounders. RESULTS: Of 144 randomised
      patients, 5 were excluded and 139 started taking abatacept (43 patients),
      rituximab (46 patients) or a different TNFi (50 patients). There were no
      significant differences between the three groups with respect to multiple
      measures of RA outcomes. However, our analysis revealed that rituximab therapy is
      significantly more cost-effective than both abatacept and TNFi over a willingness
      to-pay range of 0 to 80,000 euros. CONCLUSIONS: All three treatment options were
      similarly effective; however, when costs were factored into the treatment
      decision, rituximab was the best option available to patients whose first TNFi
      treatment failed. However, generalization of these costs to other countries
      should be undertaken carefully. TRIAL REGISTRATION: Netherlands Trial Register
      number NTR1605. Registered 24 December 2008.

PMID- 25997750
TI  - Alternating assembly of Ni-Al layered double hydroxide and graphene for high-rate
      alkaline battery cathode.
AB  - We report a Ni-Al layered double hydroxide (LDH)-graphene superlattice composite
      via alternating assembly of the exfoliated thin flakes with opposite charges that
      show stable high-rate performance for alkaline battery cathodes. 

PMID- 25997749
TI  - Membrane photoreactor treatment of 1,4-dioxane-containing textile wastewater
      effluent: Performance, modeling, and fouling control.
AB  - A membrane photoreactor (MPR) system was investigated for the purification of
      textile wastewater effluent containing 1,4-dioxane for potential reuse. The
      effects of TiO2 dosage, alkalinity, particulate matter, and sunlight radiation on
      the removal of 1,4-dioxane from the effluent were evaluated. The photocatalytic
      1,4-dioxane degradation followed pseudo-first order reaction kinetics. A
      considerably large dose of TiO2 catalyst (5 g/L) was required for maximal 1,4
      dioxane degradation by MPR. The high alkalinity (~ 550 mg/L) of the textile
      wastewater effluent negatively affected the 1,4-dioxane degradation rate, whereas
      1,4-dioxane degradation was not impacted by the presence of particulate matter.
      Solar photocatalysis of 1,4-dioxane was as effective as that achieved with UV
      lamps in the MPR, which could lead to energy savings. Continuous flow MPR was
      effective for continuous degradation of 1,4-dioxane; the unsteady- and steady
      state performances were well-predicted at various hydraulic residence times
      (HRTs). The quality of the MPR product obtained at an HRT of 8.57 h satisfied the
      drinking water guidelines. The transmembrane pressure (TMP) buildup, which is
      indicative of fouling, was dependent on the TiO2 dose and permeate flux. The TMP
      buildup was marginal at low flux, but increased dramatically beyond a flux level
      of >60 L/m(2)-h. However, the fouling layer could be sufficiently removed by
      periodic backwashing, even at an extremely high flux of 100 L/m(2)-h. The
      membrane permeability was sustained without any sign of irreversible fouling
      during MPR treatment of textile wastewater effluents.

PMID- 25997752
TI  - Ministers must halt "surreal obsession" with seven day opening, GP leader says.

PMID- 25997751
TI  - Critical care of burn patients. New approaches to old problems.
AB  - Recent publications on treatment options in critically ill patients change
      beliefs and clinical behaviors. Many dogmas, which the modern management of
      critical illness relies on, have been questioned. These publications (consensus
      articles, reviews, meta-analysis and original papers) concern some fundamental
      issues of critical care: interventions in acute respiratory distress syndrome
      (ARDS), hemodynamic monitoring, glucose control and nutritional support and
      revise our views on many key points of critical care of burn patients. 

PMID- 25997754
TI  - High Performance Non-enzymatic Glucose Sensor Based on One-Step Electrodeposited
      Nickel Sulfide.
AB  - Nanostructured NiS thin film was prepared by a one-step electrodeposition method
      and the structural, morphological characteristics of the as-prepared films were
      analyzed by X-ray diffractometry (XRD), field emission scanning electron
      microscopy (FESEM) and energy dispersive X-ray analysis (EDAX). The
      electrocatalytic activity of NiS thin film towards glucose oxidation was
      investigated by fabricating a non-enzymatic glucose sensor and the sensor
      performance was studied by cyclic voltammetry (CV) and amperometry. The
      fabricated sensor showed excellent sensitivity and low detection limit with
      values of 7.43 MUA MUM(-1)  cm(-2) and 0.32 MUM, respectively, and a response
      time of <8 s. 

PMID- 25997753
TI  - A second locus for Schneckenbecken dysplasia identified by a mutation in the gene
      encoding inositol polyphosphate phosphatase-like 1 (INPPL1).

PMID- 25997756
TI  - Prior statin use and the outcomes in patients with first-attack acute
      pancreatitis: A retrospective cohort study.
AB  - BACKGROUND: We investigated whether prior stain use before admission for a first
      attack AP would reduce the severity and mortality rate of a first-attack of AP
      with a dose-response relationship. METHODS: We conducted a retrospective cohort
      study from a tertiary medical center's database in Taiwan. We evaluated the dose
      response relationship between statin use and the first-attack of AP by defining
      the daily dose (DDD). The cumulative DDD (cDDD) was calculated as the sum of the
      dispensed DDD of any specific statin. The outcome measures in our study included
      the hospital mortality rate, duration of hospitalization, Ranson's score,
      computed tomography severity index (CTSI), and C-reactive protein (CRP) level.
      RESULTS: In our study, we enrolled 31 patients in statin group and 63 matched
      patients in control group. In the univariate analysis there was no significant
      difference between them with regard to the outcomes except the CTSI and serum
      calcium concentration. According to multivariate analysis the serum calcium
      concentration was significantly higher in the statin group, and the CTSI was
      lower in the statin group. In subgroup analysis we divided the statin group into
      two groups according to the cDDDs (<365days and >365days) and the results showed
      no significance in the demographic data, overall mortality rate, hospitalization
      days, CRP level, Ranson's score, or CTSI. CONCLUSION: Our study rejected the
      hypothesis that statins have beneficial effects on the clinical outcomes of
      patients with a first-attack of AP. However we demonstrated that statins have a
      positive effect on the CTSI.

PMID- 25997755
TI  - Acute Generalized Exanthematous Pustulosis Induced by Amoxicillin/Clavulanic
      Acid: Report of a Case Presenting With Generalized Lymphadenopathy.
AB  - Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin
      reaction, most commonly triggered by antibiotics. Although its diagnosis is based
      primarily on the presence of specific clinical and histopathologic features,
      additional in vivo (patch testing) or in vitro testing may be required,
      especially in atypical cases, to more accurately determine the causative agent.
      The authors report a histologically confirmed case of acute generalized
      exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as
      documented by subsequent patch testing, and presented with generalized painful
      lymphadenopathy, mimicking an acute infectious process. This is a very rare and
      diagnostically challenging clinical presentation of acute generalized
      exanthematous pustulosis, which has been reported, to the best of our knowledge,
      only once previously. 

PMID- 25997757
TI  - Neural plasticity, sensitive periods, and psychopathology.

PMID- 25997758
TI  - Critical periods for the neurodevelopmental processes of externalizing and
      internalizing.
AB  - Research on neurobiological development is providing insight into the nature and
      mechanisms of human neural plasticity. These mechanisms appear to support two
      different forms of developmental learning. One form of learning could be
      described as externalizing, in which neural representations are highly responsive
      to environmental influences, as the child typically operates under a mode of
      hedonic approach. A second form of learning supports internalizing, in which
      motive control separates attention and self-regulation from the immediate
      influences of the context, particularly when the child faces conditions of
      avoidance and threat. The dorsal cortical networks of externalizing are organized
      around dorsal limbic (cingulate, septal, lateral hypothalamic, hippocampal, and
      ventral striatal) circuits. In contrast, the ventral cortical networks of
      internalizing are organized around ventral limbic (anterior temporal and orbital
      cortex, extended amygdala, dorsal striatal, and mediodorsal thalamic) circuits.
      These dual divisions of the limbic system in turn self-regulate their arousal
      levels through different brain stem and forebrain neuromodulator projection
      systems, with dorsal corticolimbic networks regulated strongly by locus coeruleus
      norepinephrine and brain stem raphe nucleus serotonin projection systems, and
      ventral corticolimbic networks regulated by ventral tegmental dopamine and
      forebrain acetylcholine projections. Because the arousal control systems appear
      to regulate specific properties of neural plasticity in development, an analysis
      of these systems explains differences between externalizing and internalizing at
      multiple levels of neural and psychological self-regulation. In neuroscience, the
      concept of critical periods has been applied to times when experience is
      essential for the maturation of sensory systems. In a more general
      neuropsychological analysis, certain periods of the child's development require
      successful self-regulation through the differential capacities for externalizing
      and internalizing. 

PMID- 25997760
TI  - Sensitive periods in human social development: New insights from research on
      oxytocin, synchrony, and high-risk parenting.
AB  - Sensitive periods (SP) in behavioral development appeared in the biological
      sciences during the first decade of the 20th century, and research in animal
      models beginning in the 1950s provide terminology and evidence for SP effects.
      This paper proposes a rigorous program for human SP research and argues that the
      complexity of the human brain and variability of the human ecology necessitate
      that SP effects must be studied in humans, employ longitudinal designs starting
      at birth, test mechanism-based hypotheses based on animal studies that manipulate
      early environments, and utilize high-risk conditions as "natural experiments." In
      light of research on the molecular basis of critical periods and their sequential
      cascades, it is proposed that the oxytocin (OT) system, an ancient and
      integrative system that cross-talks with the stress, reward, immune, and brain
      stem mediated homeostatic systems and supports mammalian sociality, plays a
      unique role in experience-dependent plasticity that buttresses SP effects due to
      its (a) dendritic mode of release leading to autoregulated functioning primed by
      early experience, (b) pulsatile pattern of activity, and (c) special role in
      neural plasticity at the molecular and network assembly levels. Synchrony, the
      coordination of biology and behavior during social contact, is suggested as a
      mechanism by which SP exert their effect on OT functionality, the social brain,
      and adult sociality. Findings from four high-risk birth cohorts, each followed
      repeatedly from birth to 10 years, provide unique "natural experiments" for human
      SP research based on specific programs in animal models. These include
      prematurity (maternal proximity), multiple birth (peer rearing), postpartum
      depression (low licking and grooming), and chronic unpredictable trauma (maternal
      rotation, variable foraging demands). In each cohort, hypotheses are based on the
      missing environmental component during SP, and findings on social synchrony, OT
      functionality, stress response, emotion regulation, and mental health accord with
      the multilevel and dynamic principles of developmental psychopathology. The
      results on the potential for reparation versus chronicity following early
      deprivation highlight a flexible conceptualization of resilience based on human
      SP research. Consideration of SP effects at the molecular, endocrine, brain, and
      behavioral levels and in relation to the neural plasticity and multifinality of
      human social functions may assist in fine-tuning early detection and the
      construction of targeted individualized interventions. 

PMID- 25997761
TI  - Prenatal tobacco exposure and self-regulation in early childhood: Implications
      for developmental psychopathology.
AB  - Prenatal tobacco exposure (PTE) has a well-documented association with disruptive
      behavior in childhood, but the neurocognitive effects of exposure that underlie
      this link are not sufficiently understood. The present study was designed to
      address this gap, through longitudinal follow-up in early childhood of a
      prospectively enrolled cohort with well-characterized prenatal exposure. Three
      year-old children (n = 151) were assessed using a developmentally sensitive
      battery capturing both cognitive and motivational aspects of self-regulation. PTE
      was related to motivational self-regulation, where children had to delay approach
      to attractive rewards, but not cognitive self-regulation, where children had to
      hold information in mind and inhibit prepotent motor responses. Furthermore, PTE
      predicted motivational self-regulation more strongly in boys than in girls, and
      when propensity scores were covaried to control for confounding risk factors, the
      effect of PTE on motivational self-regulation was significant only in boys. These
      findings suggest that PTE's impact on neurodevelopment may be greater in boys
      than in girls, perhaps reflecting vulnerability in neural circuits that subserve
      reward sensitivity and emotion regulation, and may also help to explain why PTE
      is more consistently related to disruptive behavior disorders than attention
      problems. 

PMID- 25997759
TI  - Using cross-species comparisons and a neurobiological framework to understand
      early social deprivation effects on behavioral development.
AB  - Building upon the transactional model of brain development, we explore the impact
      of early maternal deprivation on neural development and plasticity in three
      neural systems: hyperactivity/impulsivity, executive function, and hypothalamic
      pituitary-adrenal axis functioning across rodent, nonhuman primate, and human
      studies. Recognizing the complexity of early maternal-infant interactions, we
      limit our cross-species comparisons to data from rodent models of artificial
      rearing, nonhuman primate studies of peer rearing, and the relations between
      these two experimental approaches and human studies of children exposed to the
      early severe psychosocial deprivation associated with institutional care. In
      addition to discussing the strengths and limitations of these paradigms, we
      present the current state of research on the neurobiological impact of early
      maternal deprivation and the evidence of sensitive periods, noting methodological
      challenges. Integrating data across preclinical animal models and human studies,
      we speculate about the underlying biological mechanisms; the differential impact
      of deprivation due to temporal factors including onset, offset, and duration of
      the exposure; and the possibility and consequences of reopening of sensitive
      periods during adolescence. 

PMID- 25997763
TI  - Brain adaptation and alternative developmental trajectories.
AB  - Resilience and adaptation in the face of early genetic or environmental risk has
      become a major interest in child psychiatry over recent years. However, we still
      remain far from an understanding of how developing human brains as a whole adapt
      to the diffuse and widespread atypical synaptic function that may be
      characteristic of some common developmental disorders. The first part of this
      paper discusses four types of whole-brain adaptation in the face of early risk:
      redundancy, reorganization, niche construction, and adjustment of developmental
      rate. The second part of the paper applies these adaptation processes
      specifically to autism. We speculate that key features of autism may be the end
      result of processes of early brain adaptation, rather than the direct
      consequences of ongoing neural pathology. 

PMID- 25997762
TI  - Early life nutrition and neural plasticity.
AB  - The human brain undergoes a remarkable transformation during fetal life and the
      first postnatal years from a relatively undifferentiated but pluripotent organ to
      a highly specified and organized one. The outcome of this developmental
      maturation is highly dependent on a sequence of environmental exposures that can
      have either positive or negative influences on the ultimate plasticity of the
      adult brain. Many environmental exposures are beyond the control of the
      individual, but nutrition is not. An ever-increasing amount of research
      demonstrates not only that nutrition shapes the brain and affects its function
      during development but also that several nutrients early in life have profound
      and long-lasting effects on the brain. Nutrients have been shown to alter opening
      and closing of critical and sensitive periods of particular brain regions. This
      paper discusses the roles that various nutrients play in shaping the developing
      brain, concentrating specifically on recently explicated biological mechanisms by
      which particularly salient nutrients influence childhood and adult neural
      plasticity. 

PMID- 25997764
TI  - Neural plasticity and the development of attention: Intrinsic and extrinsic
      influences.
AB  - The development of attention has been strongly linked to the regulation of
      emotion and behavior and has therefore been of particular interest to researchers
      aiming to better understand precursors to behavioral maladjustment. In the
      current paper, we utilize a developmental psychopathology and neural plasticity
      framework to highlight the importance of both intrinsic (i.e., infant neural
      functioning) and extrinsic (i.e., caregiver behavior) factors for the development
      of attentional control across the first year. We begin by highlighting the
      importance of attention for children's emotion regulation abilities and mental
      health. We then review the development of attention behavior and underscore the
      importance of neural development and caregiver behavior for shaping attentional
      control. Finally, we posit that neural activation associated with the development
      of the executive attention network may be one mechanism through which maternal
      caregiving behavior influences the development of infants' attentional control
      and subsequent emotion regulation abilities known to be influential to childhood
      psychopathology. 

PMID- 25997765
TI  - Lexical processing deficits in children with developmental language disorder: An
      event-related potentials study.
AB  - Lexical processing deficits in children with developmental language disorder
      (DLD) have been postulated to arise as sequelae of their grammatical deficits
      (either directly or via compensatory mechanisms) and vice versa. We examined
      event-related potential indices of lexical processing in children with DLD (n =
      23) and their typically developing peers (n = 16) using a picture-word matching
      paradigm. We found that children with DLD showed markedly reduced N400 amplitudes
      in response both to auditorily presented words that had initial phonological
      overlap with the name of the pictured object and to words that were not
      semantically or phonologically related to the pictured object. Moreover, this
      reduction was related to behavioral indices of phonological and lexical but not
      grammatical development. We also found that children with DLD showed a depressed
      phonological mapping negativity component in the early time window, suggesting
      deficits in phonological processing or early lexical access. The results are
      partially consistent with the overactivation account of lexical processing
      deficits in DLD and point to the relative functional independence of
      lexical/phonological and grammatical deficits in DLD, supporting a
      multidimensional view of the disorder. The results also, although indirectly,
      support the neuroplasticity account of DLD, according to which language
      impairment affects brain development and shapes the specific patterns of brain
      responses to language stimuli. 

PMID- 25997767
TI  - The theory of latent vulnerability: Reconceptualizing the link between childhood
      maltreatment and psychiatric disorder.
AB  - Maltreatment in childhood is associated with a significantly increased likelihood
      of psychiatric disorder that endures across the life span. If disorders emerge
      they tend to be more severe and less responsive to treatment. We introduce the
      concept of latent vulnerability as a way of conceptualizing the nature of this
      psychiatric risk. We argue that vulnerability to mental health problems can be
      understood as changes in a suite of neurocognitive systems that reflect
      adaptation or altered calibration to early neglectful or maltreating
      environments. Altered threat processing is presented as one exemplar candidate
      system. Heightened neurocognitive vigilance to threat is argued to reflect a
      calibration to an early at-risk environment that becomes maladaptive (and
      instantiates vulnerability) in the longer term. Other neurocognitive domains,
      including reward and memory processing, represent equally promising candidates
      for indexing latent vulnerability and warrant future enquiry. We suggest that the
      operationalization of latent vulnerability has the potential to guide a
      preventative psychiatry approach. Intervention currently occurs at two stages
      when maltreatment is confirmed: first, by addressing issues of risk; and second,
      by providing clinical intervention if a child meets criteria for psychiatric
      disorder. We argue that indexing latent vulnerability represents a third
      intervention opportunity, with the potential to target an indicated prevention
      approach for the most vulnerable children, offsetting risk trajectories before
      psychiatric disorders emerge. 

PMID- 25997768
TI  - Beating the brain about abuse: Empirical and meta-analytic studies of the
      association between maltreatment and hippocampal volume across childhood and
      adolescence.
AB  - We present new empirical data and meta-analytic evidence for the association of
      childhood maltreatment with reduced hippocampal volume. In Study 1, we examined
      the effects of maltreatment experiences reported during the Adult Attachment
      Interview on hippocampal volume in female twin pairs. We found that reduced
      hippocampal volume was related to childhood maltreatment. In addition,
      individuals who reported having experienced maltreatment at older ages had larger
      reductions in hippocampal volume compared to individuals who reported
      maltreatment in early childhood. In Study 2, we present the results of a meta
      analysis of 49 studies (including 2,720 participants) examining hippocampal
      volume in relation to experiences of child maltreatment, and test the moderating
      role of the timing of the maltreatment, the severity of maltreatment, and the
      time after exposure to maltreatment. The results of the meta-analysis confirmed
      that experiences of childhood maltreatment are associated with a reduction in
      hippocampal volume and that the effects of maltreatment are more pronounced when
      the maltreatment occurs in middle childhood compared to early childhood or
      adolescence. 

PMID- 25997769
TI  - Childhood maltreatment and its effect on neurocognitive functioning: Timing and
      chronicity matter.
AB  - Childhood maltreatment represents a complex stressor, with the developmental
      timing, duration, frequency, and type of maltreatment varying with each child
      (Barnett, Manly, & Cicchetti, 1993; Cicchetti & Manly, 2001). Multiple brain
      regions and neural circuits are disrupted by the experience of child maltreatment
      (Cicchetti & Toth, in press; DeBellis et al., 2002; McCrory & Viding, 2010;
      Teicher, Anderson, & Polcari, 2012). These neurobiological compromises indicate
      the impairment of a number of important cognitive functions, including working
      memory and inhibitory control. The present study extends prior research by
      examining the effect of childhood maltreatment on neurocognitive functioning
      based on developmental timing of maltreatment, including onset, chronicity, and
      recency, in a sample of 3- to 9-year-old nonmaltreated (n = 136) and maltreated
      children (n = 223). Maltreated children performed more poorly on inhibitory
      control and working-memory tasks than did nonmaltreated children. Group
      differences between maltreated children based on the timing of maltreatment and
      the chronicity of maltreatment also were evident. Specifically, children who were
      maltreated during infancy, and children with a chronic history of maltreatment,
      exhibited significantly poorer inhibitory control and working-memory performance
      than did children without a history of maltreatment. The results suggest that
      maltreatment occurring during infancy, a period of major brain organization,
      disrupts normative structure and function, and these deficits are further
      instantiated by the prolonged stress of chronic maltreatment during the early
      years of life. 

PMID- 25997766
TI  - Exposure to early adversity: Points of cross-species translation that can lead to
      improved understanding of depression.
AB  - The relationship between developmental exposure to adversity and affective
      disorders is reviewed. Adversity discussed herein includes physical and sexual
      abuse, neglect, or loss of a caregiver in humans. While these stressors can occur
      at any point during development, the unique temporal relationship to specific
      depressive symptoms was the focus of discussion. Further influences of stress
      exposure during sensitive periods can vary by gender and duration of abuse as
      well. Data from animal studies are presented to provide greater translational and
      causal understanding of how sensitive periods, different types of psychosocial
      stressors, and sex interact to produce depressive-like behaviors. Findings from
      maternal separation, isolation rearing, chronic variable stress, and peer-peer
      rearing paradigms clarify interpretation about how various depressive behaviors
      are influenced by age of exposure. Depressive behaviors are broken down into the
      following categories: mood and affect, anhedonia, energy, working memory, sleep
      wake, appetite changes, suicide, and general malaise. Cross-species evidence from
      humans, nonhuman primates, rats, and mice within each of these categories is
      discussed. In conclusion, sensitive periods for affective-related behaviors
      (anxiety, mood, and controllability) occur earlier in life, while other aspects
      of depression are associated with adversity later during adolescence. 

PMID- 25997770
TI  - Plasticity of risky decision making among maltreated adolescents: Evidence from a
      randomized controlled trial.
AB  - Childhood maltreatment has lasting negative effects throughout the life span.
      Early intervention research has demonstrated that these effects can be remediated
      through skill-based, family-centered interventions. However, less is known about
      plasticity during adolescence, and whether interventions are effective many years
      after children experience maltreatment. This study investigated this question by
      examining adolescent girls' ability to make advantageous decisions in the face of
      risk using a validated decision-making task; performance on this task has been
      associated with key neural regions involved in affective processing and executive
      functioning. Maltreated foster girls (n = 92), randomly assigned at age 11 to
      either an intervention designed to prevent risk-taking behaviors or services as
      usual (SAU), and nonmaltreated age and socioeconomic status matched girls living
      with their biological parent(s) (n = 80) completed a decision-making task (at age
      15-17) that assessed risk taking and sensitivity to expected value, an index of
      advantageous decision making. Girls in the SAU condition demonstrated the
      greatest decision-making difficulties, primarily for risks to avoid losses. In
      the SAU group, frequency of neglect was related to greater difficulties in this
      area. Girls in the intervention condition with less neglect performed similarly
      to nonmaltreated peers. This research suggests that early maltreatment may impact
      decision-making abilities into adolescence and that enriched environments during
      early adolescence provide a window of plasticity that may ameliorate these
      negative effects. 

PMID- 25997771
TI  - Child maltreatment, inflammation, and internalizing symptoms: Investigating the
      roles of C-reactive protein, gene variation, and neuroendocrine regulation.
AB  - Prior research has found inconsistent evidence regarding the association among
      childhood adversity, inflammation, and internalizing symptoms, perhaps because
      previous studies have yet to adequately integrate important factors such as the
      timing of the adversity, genetic variation, and other relevant processes such as
      neuroendocrine regulation. The aims of the present study were threefold: (a) to
      determine whether the effect of the timing of child maltreatment on C-reactive
      protein (CRP), an inflammatory marker, varies by CRP gene variation; (b) to
      explore whether links between salivary CRP and childhood internalizing symptoms
      depend on the presence and timing of maltreatment experiences; and (c) to
      investigate the role of CRP in the relations between child neuroendocrine
      regulation and internalizing symptoms and examine whether these associations are
      moderated by the presence and timing of child maltreatment. Participants included
      a sample of 267 maltreated and 222 nonmaltreated children (M age = 9.72, SD =
      0.99; 52.4% male; 66% African American) who attended a summer day camp research
      program designed for school-aged low-income children. Department of Human
      Services records were examined to determine the onset and recency of maltreatment
      for children in the maltreated group. The results indicated that among children
      with recent onset maltreatment, those with at least one A allele from CRP single
      nucleotide polymorphism rs1417938 evidenced significantly higher CRP levels
      compared to recently maltreated children carrying the TT genotype. Moreover,
      higher levels of CRP were associated with higher levels of internalizing symptoms
      only for recently maltreated children. Finally, we did not find support for
      salivary CRP as a mechanism in the relation between neuroendocrine regulation and
      childhood internalizing symptoms. Our findings highlight the importance of the
      timing of child maltreatment and have important implications for characterizing
      variability in inflammation and internalizing symptoms among youth. 

PMID- 25997772
TI  - Adversity in preschool-aged children: Effects on salivary interleukin-1beta.
AB  - Exposure to early life adversity is linked to impaired affective, cognitive, and
      behavioral functioning and increases risk for various psychiatric and medical
      conditions. Stress-induced increases in pro-inflammatory cytokines may be a
      biological mechanism of these effects. Few studies have examined cytokine levels
      in children experiencing early life adversity, and very little research has
      investigated cytokines or other markers of inflammation in saliva. In the present
      study, we examined salivary interleukin (IL)-1beta and C-reactive protein (CRP)
      levels in relation to stress exposure in 40 children aged 3 to 5 years who were
      enrolled in a larger study of early life adversity. Childhood maltreatment status
      was assessed via review of child welfare records. Contextual stress exposure,
      traumatic life event history, and symptoms of psychopathology were assessed via
      caregiver interviews at a home visit. In a subsequent visit, salivary IL-1beta
      and CRP were obtained before and after participation in four emotion-eliciting
      tasks. The number of past-month contextual stressors, lifetime contextual
      stressors, and traumatic life events each demonstrated a significant main effect
      on IL-1beta. Baseline IL-1beta was positively associated with each of the
      significant main-effect adversities. Postchallenge IL-1beta displayed positive
      associations with each adversity variable, but these were not significant. CRP
      was not significantly associated with any of the adversity variables. Given the
      evidence suggesting the involvement of IL-1beta in the neuropathology of
      psychiatric conditions, these results may have important implications for
      developmental outcomes. 

PMID- 25997774
TI  - Developmental psychopathology in an era of molecular genetics and neuroimaging: A
      developmental neurogenetics approach.
AB  - The emerging field of neurogenetics seeks to model the complex pathways from gene
      to brain to behavior. This field has focused on imaging genetics techniques that
      examine how variability in common genetic polymorphisms predict differences in
      brain structure and function. These studies are informed by other complimentary
      techniques (e.g., animal models and multimodal imaging) and have recently begun
      to incorporate the environment through examination of Imaging Gene * Environment
      interactions. Though neurogenetics has the potential to inform our understanding
      of the development of psychopathology, there has been little integration between
      principles of neurogenetics and developmental psychopathology. The paper
      describes a neurogenetics and Imaging Gene * Environment approach and how these
      approaches have been usefully applied to the study of psychopathology. Six tenets
      of developmental psychopathology (the structure of phenotypes, the importance of
      exploring mechanisms, the conditional nature of risk, the complexity of
      multilevel pathways, the role of development, and the importance of who is
      studied) are identified, and how these principles can further neurogenetics
      applications to understanding the development of psychopathology is discussed. A
      major issue of this piece is how neurogenetics and current imaging and molecular
      genetics approaches can be incorporated into developmental psychopathology
      perspectives with a goal of providing models for better understanding pathways
      from among genes, environments, the brain, and behavior. 

PMID- 25997773
TI  - Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter
      and exposure to adversity in preschool-aged children.
AB  - Epigenetic modifications to the genome are a key mechanism involved in the
      biological encoding of experience. Animal studies and a growing body of
      literature in humans have shown that early adversity is linked to methylation of
      the gene for the glucocorticoid receptor (GR), which is a key regulator of the
      hypothalamic-pituitary-adrenal axis as well as a broad range of physiological
      systems including metabolic and immune function. One hundred eighty-four families
      participated, including n = 74 with child welfare documentation of moderate
      severe maltreatment in the past 6 months. Children ranged in age from 3 to 5
      years, and were racially and ethnically diverse. Structured record review and
      interviews in the home were used to assess a history of maltreatment, other
      traumas, and contextual life stressors, and a composite variable assessed the
      number exposures to these adversities. Methylation of regions 1(D), 1(F), and
      1(H) of the GR gene was measured via sodium bisulfite pyrosequencing. The
      composite measure of adversity was positively correlated with methylation at
      exons 1(D) and 1(F) in the promoter of the GR gene. Individual stress measures
      were significantly associated with a several CpG sites in these regions. GR gene
      methylation may be a mechanism of the biobehavioral effects of adverse exposures
      in young children.

PMID- 25997777
TI  - Thymidylate synthase inspired biomodel reagent for the conversion of uracil to
      thymine.
AB  - Inspired by TSase catalysis for dUMP conversion to dTMP, a biomodel reagent is
      developed. The presence of NH2, Gly-(S)-Cys and (S)-oxiran methyl, at C5, C4 and
      N-10 of acridine, respectively, in addition to the pH of the reaction mixture,
      allows for good complementary inter- and intra-molecular interactions and chiral
      discrimination for the reagent to achieve conversion of uracil to thymine. 

PMID- 25997778
TI  - Low- and High-Resistance Exercise: Long-Term Adherence and Motivation among Older
      Adults.
AB  - BACKGROUND: In terms of motivation and long-term adherence, low-resistance
      exercise might be more suitable for older adults than high-resistance exercise.
      However, more data are needed to support this claim. OBJECTIVE: The objective was
      to investigate the effect of low- and high-resistance exercise protocols on long
      term adherence and motivation. METHODS: This study was designed as an exploratory
      24-week follow-up of a randomized 12-week resistance training intervention in
      older adults. Participants were free to decide whether or not they continued
      resistance training at their own expense following the intervention. Fifty-six
      older adults were randomly assigned to HIGH [2 * 10-15 repetitions at 80% of one
      repetition maximum (1RM)], LOW (1 * 80-100 repetitions at 20% of 1RM), or LOW+ (1
      * 60 repetitions at 20% of 1RM + 1 * 10-20 repetitions at 40% 1RM). Motivation,
      self-efficacy and the perceived barriers for continuing resistance exercise were
      measured after cessation of each supervised intervention and at follow-up, while
      long-term adherence was probed retrospectively at follow-up. RESULTS:
      Participants reported high levels of self-determined motivation before, during,
      and after the supervised intervention, with no differences between groups (p >
      0.05). Nevertheless, only few participants continued strength training after the
      intervention: 17% in HIGH, 21% in LOW+, and 11% in LOW (p > 0.05). The most
      commonly reported barriers for continuing resistance exercise were perceived lack
      of time (46%), being more interested in other physical activities (40%), seasonal
      reasons (40%), and financial cost (28%). CONCLUSION: The results suggest no
      difference in long-term adherence after the end of a supervised exercise
      intervention at high or low external resistances. Long-term adherence was limited
      despite high levels of self-determined motivation during the interventions. These
      findings highlight the importance of further research on developing strategies to
      overcome barriers of older adults to adhere to resistance exercise without
      supervision.

PMID- 25997776
TI  - Epigenetic pathways through which experiences become linked with biology.
AB  - This article highlights the defining principles, progress, and future directions
      in epigenetics research in relation to this Special Issue. Exciting studies in
      the fields of neuroscience, psychology, and psychiatry have provided new insights
      into the epigenetic factors (e.g., DNA methylation) that are responsive to
      environmental input and serve as biological pathways in behavioral development.
      Here we highlight the experimental evidence, mainly from animal models, that
      factors such as psychosocial stress and environmental adversity can become
      encoded within epigenetic factors with functional consequences for brain
      plasticity and behavior. We also highlight evidence that epigenetic marking of
      genes in one generation can have consequences for future generations (i.e.,
      inherited), and work with humans linking epigenetics, cognitive dysfunction, and
      psychiatric disorder. Though epigenetics has offered more of a beginning than an
      answer to the centuries-old nature-nurture debate, continued research is certain
      to yield substantial information regarding biological determinants of central
      nervous system changes and behavior with relevance for the study of developmental
      psychopathology. 

PMID- 25997779
TI  - Hepatitis B virus genotyping in chronic hepatitis B patients in southwestern
      Saudi Arabia.
AB  - The distribution of hepatitis B virus genotypes in Saudi Arabia is largely
      unknown. To the best of our knowledge there are no data available about HBV
      genotypes in southwestern region of the country. This study aimed to determine
      the epidemiologic distribution of hepatitis B virus genotypes in chronic
      hepatitis B patients in southwestern region, and to verify possible correlations
      between these genotypes and the clinical symptoms. A total of 160 patients with
      chronic hepatitis B infection were enrolled in this study. Sera were tested for
      liver function tests, hepatitis B virus markers and DNA load by standard
      procedures. HBV genotyping was performed by 2-tube nested PCR for determination
      of six genotypes (A-F). Genotype D was the most common, found in 135 (84.4%)
      patients, followed by A (18; 11.3%) and E (7; 4.3%). The rate of HBeAg positivity
      in genotype D patients was significantly lower compared with that in genotype A
      and E patients (p=0.01). There was no significant association between HBV
      genotypes and age, gender, liver function tests, or HBV DNA load. Genotypes D and
      E were predominant in chronic hepatitis B patients in southwestern Saudi Arabia.
      Awareness of hepatitis B virus serologic and genotypic patterns might help in the
      formulation of management plans, predicting clinical outcomes and updating
      prevention strategies. 

PMID- 25997775
TI  - Dysplasticity, metaplasticity, and schizophrenia: Implications for risk, illness,
      and novel interventions.
AB  - In this paper, we review the history of the concept of neuroplasticity as it
      relates to the understanding of neuropsychiatric disorders, using schizophrenia
      as a case in point. We briefly review the myriad meanings of the term
      neuroplasticity, and its neuroscientific basis. We then review the evidence for
      aberrant neuroplasticity and metaplasticity associated with schizophrenia as well
      as the risk for developing this illness, and discuss the implications of such
      understanding for prevention and therapeutic interventions. We argue that the
      failure and/or altered timing of plasticity of critical brain circuits might
      underlie cognitive and deficit symptoms, and may also lead to aberrant plastic
      reorganization in other circuits, leading to affective dysregulation and
      eventually psychosis. This "dysplastic" model of schizophrenia can suggest
      testable etiology and treatment-relevant questions for the future. 

PMID- 25997780
TI  - Evaluation of phenotypic tests to detect carbapenem-resistant Enterobacteriaceae
      in colonized patients hospitalized in intensive care units.
AB  - In this study, we aimed to evaluate the performance of different phenotypic tests
      to detect carbapenem-resistant Enterobacteriaceae. Three different phenotypic
      methods were evaluated: (1) combined-disk test of meropenem plus phenylboronic
      acid or EDTA reading after 24h and 48h; (2) selective/chromogenic read after 24h
      and after 48h; and (3) overnight selective enrichment broth containing 10MUg
      ertapenem disk followed by culture on MacConkey agar. A positive result in at
      least one of the methods was submitted to PCR for blaNDM-1, blaOXA-48, blaKPC,
      blaSPM-1, blaIMP, and blaGES detection. Carbapenem-resistant Enterobacteriaceae
      was detected in 31 (30.4%) of 102 rectal swabs evaluated. All isolates showed to
      be KPC-2-producing organisms. Results showed excellent agreement among the
      evaluated tests (positive and negative) (kappa=0.88). It is important to state
      that combined-disk test with phenylboronic acid is not suitable for bacterial
      identification/isolation. Conversely, selective/chromogenic agar after 48h of
      incubation showed to be a useful tool, with the advantage of presumptive
      bacterial identification. 

PMID- 25997781
TI  - Use of new antiretroviral drugs and classes in Bahia, Brazil: a real life
      experience on salvage therapy of AIDS patients.
AB  - Antiretroviral therapy has significantly evolved in the last decade, with an
      increasing number of new drugs and classes. Currently, even heavily experienced
      patients can be successfully treated with new regimens. In Brazil, the recent
      incorporation of some new antiretroviral drugs made it possible to suppress HIV
      plasma viremia in most treated patients, with significant benefits in terms of
      quality of life and survival. However, little has been published on outcomes of
      patients under new drugs-based regimens. We reviewed the safety and efficacy of
      antiretroviral regimens using recently introduced drugs in Bahia. Our results
      confirm that patients using darunavir, raltegravir, enfuvirtide, or etravirine
      presented with a high rate of virological suppression without significant adverse
      events, after one year of follow-up. 

PMID- 25997782
TI  - Membranous glomerulonephritis secondary to syphilis.

PMID- 25997783
TI  - Spread of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa
      clones in patients with ventilator-associated pneumonia in an adult intensive
      care unit at a university hospital.
AB  - BACKGROUND: In Brazil, ventilator-associated pneumonia (VAP) caused by carbapenem
      resistant Acinetobacter baumannii and Pseudomonas aeruginosa isolates are
      associated with significant mortality, morbidity and costs. Studies on the clonal
      relatedness of these isolates could lay the foundation for effective infection
      prevention and control programs. OBJECTIVES: We sought to study the
      epidemiological and molecular characteristics of A. baumannii vs. P. aeruginosa
      VAP in an adult intensive care unit (ICU). METHODS: It was conducted a cohort
      study of patients with VAP caused by carbapenem resistant A. baumannii and P.
      aeruginosa during 14 months in an adult ICU. Genomic studies were used to
      investigate the clonal relatedness of carbapenem resistant OXA-23-producing A.
      baumannii and P. aeruginosa clinical isolates. The risk factors for acquisition
      of VAP were also evaluated. Clinical isolates were collected for analysis as were
      samples from the environment and were typed using pulsed field gel
      electrophoresis. RESULTS: Multivariate logistic regression analysis identified
      trauma diagnosed at admission and inappropriate antimicrobial therapy as
      independent variables associated with the development of A. baumannii VAP and
      hemodialysis as independent variable associated with P. aeruginosa VAP. All
      carbapenem resistant clinical and environmental isolates of A. baumannii were OXA
      23 producers. No MBL-producer P. aeruginosa was detected. Molecular typing
      revealed a polyclonal pattern; however, clone A (clinical) and H (surface) were
      the most frequent among isolates of A. baumannii tested, with a greater pattern
      of resistance than other isolates. In P. aeruginosa the most frequent clone I was
      multi-sensitive. CONCLUSION: These findings suggest the requirement of constant
      monitoring of these microorganisms in order to control the spread of these clones
      in the hospital environment.

PMID- 25997784
TI  - Hepatitis B virus reactivation after treatment for hepatitis C in hemodialysis
      patients with HBV/HCV coinfection.
AB  - In coinfected HBV/HCV patients, HBV replication is usually suppressed by HCV over
      the time. No study to date has evaluated the HBV viremia in long-term follow-up
      after HCV treatment in hemodialysis patients with HBV/HCV coinfection. This study
      aimed to assess the evolution of HBV viremia after HCV treatment in this special
      population. Ten hemodialysis patients with HBV/HCV coinfection with dominant HCV
      infection (HBV lower than 2000 IU/mL) and significant fibrosis were treated with
      interferon-alpha 3 MU 3*/week for 12 months and could be followed for at least 36
      months after HCV treatment. Six cases of HBV reactivation (60%) during follow-up
      were observed and 5/6 had been successfully treated for HCV. Patients with HBV
      reactivation received anti-HBV therapy. Our preliminary findings indicate that
      treatment of hepatitis C in HBV/HCV coinfected hemodialysis patients may favor
      HBV reactivation. Thus, continued monitoring of HBV viremia must be recommended
      and prompt anti-HBV therapy should be implemented.

PMID- 25997786
TI  - Transnasal Transsphenoidal Surgical Method in Pediatric Pituitary Adenomas.
AB  - AIM: To evaluate the clinical outcome in a 13-year consecutive series of children
      operated for pituitary adenomas with transnasal transsphenoidal surgery. METHODS:
      All patients <18 years who were operated on at our center by transsphenoidal
      surgery for pediatric pituitary adenomas were included in the study. Clinical
      features, hormonal profile, radiology, surgical approach, results and
      complications were analyzed. RESULTS: Eighteen patients (90%) had functional
      pituitary adenomas and 2 (10%) patients had nonfunctional pituitary adenoma. The
      most common type was prolactin-secreting adenoma (n = 12), followed by
      corticotropinoma (n = 4), growth hormone-secreting adenoma (n = 2), and
      nonfunctioning adenoma (n = 2). Prolactin-secreting adenomas in children occurred
      more commonly with suprasellar expansion than did other adenomas. CONCLUSION:
      Transsphenoidal surgery was effective for decompression of suprasellar extension
      and relieved the chiasmal compression immediately. Prolactin-secreting tumors
      required postoperative medical therapy for persistently elevated prolactin
      levels.

PMID- 25997785
TI  - Association between tongue coating thickness and clinical characteristics among
      idiopathic membranous nephropathy patients.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tongue coating diagnosis is a useful tool to
      examine the changes of a human body in Chinese Medicine. Tongue coating varies in
      thickness in kidney disease. However, little information exists regarding the
      association between clinical characters and tongue coating thickness in CKD
      patients. AIM OF THE STUDY: This study was carried out to determine whether there
      is an association between tongue coating thickness and laboratory, histological
      variables in idiopathic membranous nephropathy patients: one group with thin
      tongue coating, the other with thick tongue coating. MATERIALS AND METHODS:
      During July 2012-March 2014, idiopathic membranous nephropathy patients(CKD 1-2
      stage) with tongue coating thickness Score <=7, or >=11, were enrolled as thin
      tongue coating group or thick tongue coating group, from Hangzhou Hospital of
      TCM. Laboratory variables (Hemoglobin (Hb), albumin (Alb); eGFR; alanine
      transferase (ALT); aspartate aminotransferase (AST); triglyceride (TG); total
      cholesterone (TC); high density lipoprotein (HDL); low density lipoprotein (LDL);
      immunoglobin A, G, M; Complement 3, 4) and renal histological data (glomerular
      lesions; tubular-interstitial damage) were compared, between these two groups.
      RESULTS: 12 idiopathic MN patients (CKD 1-2 stage) with thin tongue coating
      (tongue coating thickness score <=7) and 11 with thick tongue coating (tongue
      coating thickness score >=11) were enrolled in our study. We found a significant
      lower level of TC and LDL, a significant lower level of AST, ALT in those thick
      tongue coating patients, compared with thin. No significant difference was
      observed in pathological lesion between thick and thin tongue coating patients.
      CONCLUSION: Tongue coating thickness is associated with lipid metabolism in
      idiopathic MN patients (CKD 1-2 stages).

PMID- 25997788
TI  - Fluoride-assisted activation of calcium carbide: a simple method for the
      ethynylation of aldehydes and ketones.
AB  - The fluoride-assisted ethynylation of ketones and aldehydes is described using
      commercially available calcium carbide with typically 5 mol % of TBAF.3H2O as the
      catalyst in DMSO. Activation of calcium carbide by fluoride is thought to
      generate an acetylide "ate"-complex that readily adds to carbonyl groups.
      Aliphatic aldehydes and ketones generally provide high yields, whereas aromatic
      carbonyls afford propargylic alcohols with moderate to good yields. The use of
      calcium carbide as a safe acetylide ion source along with economic amounts of
      TBAF.3H2O make this procedure a cheap and operationally simple method for the
      preparation of propargylic alcohols. 

PMID- 25997787
TI  - Continuous Renal Replacement Therapy in Successful Treatment of a Patient With
      Hyperlipidemic Acute Pancreatitis.

PMID- 25997790
TI  - Binaural auditory outcomes in patients with postlingual profound unilateral
      hearing loss: 3 years after cochlear implantation.
AB  - The value of cochlear implants (CI) in patients with profound unilateral hearing
      loss (UHL) and tinnitus has recently been investigated. The authors previously
      demonstrated the feasibility of CI in a 12- month outcome study in a prospective
      UHL cohort. The aim of this study was to investigate the binaural auditory
      outcomes in this cohort 36 months after CI surgery. The 36-month outcome was
      evaluated in 22 CI users with postlingual UHL and severe tinnitus. Twelve
      subjects had contralateral normal hearing (single-sided deafness - SSD group) and
      10 subjects had a contralateral, mild to moderate hearing loss and used a hearing
      aid (asymmetric hearing loss - AHL group). Speech perception in noise was
      assessed in two listening conditions: the CIoff and the CIon condition. The
      binaural summation effect (S0N0), binaural squelch effect (S0NCI) and the
      combined head shadow effect (SCIN0) were investigated. Subjective benefit in
      daily life was assessed by means of the Speech, Spatial and Qualities of Hearing
      Scale (SSQ). At 36 months, a significant binaural summation effect was observed
      for the study cohort (2.00, SD 3.82 dB; p < 0.01) and for the AHL subgroup (3.34,
      SD 5.31 dB; p < 0.05). This binaural effect was not significant 12 months after
      CI surgery. A binaural squelch effect was significant for the AHL subgroup at 12
      months (2.00, SD 4.38 dB; p < 0.05). A significant combined head shadow and
      squelch effect was also noted in the spatial configuration SCIN0 for the study
      cohort (4.00, SD 5.89 dB; p < 0.01) and for the AHL subgroup (5.67, SD 6.66 dB; p
      < 0.05). The SSQ data show that the perceived benefit in daily life after CI
      surgery remains stable up to 36 months at CIon. CI can significantly improve
      speech perception in noise in patients with UHL. The positive effects of CIon
      speech perception in noise increase over time up to 36 months after CI surgery.
      Improved subjective benefit in daily life was also shown to be sustained in these
      patients.

PMID- 25997789
TI  - Functional analysis of Hairy genes in Xenopus neural crest initial specification
      and cell migration.
AB  - BACKGROUND: Neural crest formation is one of the fundamental processes in the
      early stages of embryonic development in vertebrates. This transient and
      multipotent embryonic cell population is able to generate a variety of tissues
      and cell types in the adult body. hairy genes are transcription factors that
      contain a basic helix-loop-helix domain which binds to DNA. In Xenopus three
      hairy genes are known: hairy1, hairy2a, and hairy2b. The requirement of hairy
      genes was explored in early neural crest development although the late
      requirements of these genes during neural crest maintenance, migration and
      derivatives formation are still unknown. RESULTS: In this work, we extended the
      analysis of Xenopus hairy genes expression patterns and described new domains of
      expression. Functional analysis showed that hairy genes are required for the
      induction and migration of the neural crest and for the control of apoptosis.
      Moreover, we showed that hairy genes function as transcriptional repressors and
      that they are down-regulated by bone morphogenetic protein-Smad signaling and
      positively regulated by the Notch/Delta-Su(h) pathway. CONCLUSIONS: Our results
      indicate that hairy genes have a functional equivalence between them and that
      they are required for multiple processes during neural crest development.

PMID- 25997791
TI  - Let-7, ascendant miR-181a.

PMID- 25997792
TI  - Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast
      cancer: A comparative non-inferiority study.
AB  - AIMS: The gold standard for detection of Sentinel Lymph Nodes (SLN) is a combined
      radioisotope and blue dye breast injection, using a gamma probe (GP). A new, non
      radioactive method was developed, using a tracer (Sienna+((r))) of
      superparamagnetic iron oxide (SPIO) nanoparticles and a manual magnetometer
      (SentiMag((r))) (SM). The IMAGINE study was designed to show the non-inferiority
      of SM compared to GP, for the detection of SLN in breast cancer patients with SLN
      biopsy indication. METHODS: From November 2013 to June 2014, 181 patients were
      recruited, and 321 nodes were excised and assessed ex-vivo. Readings from both SM
      and GP devices were recorded during transcutaneous, intraoperative, and ex-vivo
      detection attempts. RESULTS: At the patient level, ex-vivo detection rates
      (primary variable) with SM and GP were 97.8% and 98.3% (concordance rate 99.4%).
      Transcutaneous and intraoperative detection rates were 95.5% vs 97.2%, and 97.2%
      vs 97.8% for SM and GP respectively (concordance rates > 97%). At the node level,
      intraoperative and ex-vivo detection rates were 92.5% vs 89.3% and 91.0% vs 86.3%
      for SM and GP respectively. In all cases the non-inferiority of SM compared to SM
      was shown by ruling out a predefined non-inferiority margin of 5%. CONCLUSIONS:
      Our study showed the non-inferiority of SM as compared to GP. Moreover, the ex
      vivo and intraoperative detection rates at the node level were slightly higher
      with SM.

PMID- 25997793
TI  - The enduring value of Ganti's chemoton model and life criteria: Heuristic pursuit
      of exact theoretical biology.
AB  - Ganti's chemoton model of the minimal chemical organization of living systems and
      life criteria for the living state and a living world are characterized. It is
      argued that these are better interpreted as part of a heuristic pursuit of an
      exact theoretical biology than as a "definition of life." Several problems with
      efforts to define life are discussed. Clarifying the proper use of Ganti's ideas
      to serve constructive engineering idealizations helps to show their enduring
      value.

PMID- 25997794
TI  - Statistical properties and error threshold of quasispecies on single-peak
      Gaussian-distributed fitness landscapes.
AB  - The stochastic Eigen model proposed by Feng et al. (2007) (Journal of Theoretical
      Biology, 246, 28) showed that error threshold is no longer a phase transition
      point but a crossover region whose width depends on the strength of the random
      fluctuation in an environment. The underlying cause of this phenomenon has not
      yet been well examined. In this article, we adopt a single peak Gaussian
      distributed fitness landscape instead of a constant one to investigate and
      analyze the change of the error threshold and the statistical property of the
      quasi-species population. We find a roughly linear relation between the width of
      the error threshold and the fitness fluctuation strength. For a given quasi
      species, the fluctuation of the relative concentration has a minimum with a
      normal distribution of the relative concentration at the maximum of the averaged
      relative concentration, it has however a largest value with a bimodal
      distribution of the relative concentration near the error threshold. The above
      results deepen our understanding of the quasispecies and error threshold and are
      heuristic for exploring practicable antiviral strategies. 

PMID- 25997795
TI  - Phosphoribosylphosphate and phosphoribosylnicotinate pairing with
      phosphoribosylamine at the origin of the RNA world.
AB  - The gap between prebiotic chemistry and the RNA origin of life lies in the nature
      of the pre-ribonucleotides that initiated replication-like activity. The present
      paper illustrates how the constraints for self-catalytic synthesis of the
      building blocks point to ionic pairing of the first pre-ribonucleotides and point
      to a central role for nicotinate. 

PMID- 25997796
TI  - Stem cell regulation: Implications when differentiated cells regulate symmetric
      stem cell division.
AB  - We use a mathematical model to show that if symmetric stem cell division is
      regulated by differentiated cells, then changes in the population dynamics of the
      differentiated cells can lead to changes in the population dynamics of the stem
      cells. More precisely, the relative fitness of the stem cells can be affected by
      modifying the death rate of the differentiated cells. This result is interesting
      because stem cells are less sensitive than differentiated cells to environmental
      factors, such as medical therapy. Our result implies that stem cells can be
      manipulated indirectly by medical treatments that target the differentiated
      cells. 

PMID- 25997797
TI  - Radiosurgery for Cerebral Arteriovenous Malformations in Elderly Patients: Effect
      of Advanced Age on Outcomes After Intervention.
AB  - OBJECTIVE: Cerebral arteriovenous malformations (AVM) are infrequently diagnosed
      and treated in elderly patients (age, >60 years). We hypothesize that, in
      contrast to AVM surgical outcomes, radiosurgery outcomes are not adversely
      affected by increased age. The goals of this case-control study are to analyze
      the radiosurgery outcomes for elderly patients with AVMs and determine the effect
      of elderly age on AVM radiosurgery outcomes. METHODS: We evaluated a prospective
      database of patients with AVMs treated with radiosurgery from 1989 to 2013.
      Elderly patients with AVM (age, >= 60 years) with radiologic follow-up of >= 2
      years or nidus obliteration were selected for analysis, and matched, in a 1:1
      fashion and blinded to outcome, to adult nonelderly patients with AVM (age, <60
      years). Statistical analyses were performed to determine actuarial obliteration
      rates and evaluate the relationship between elderly age and AVM radiosurgery
      outcomes. RESULTS: The matching processes yielded 66 patients in each of the
      elderly and nonelderly AVM cohorts. In the elderly AVM cohort, the actuarial AVM
      obliteration rates at 3, 5, and 10 years were 37%, 65%, and 77%, respectively;
      the rates of radiologically evident, symptomatic, and permanent radiation-induced
      changes were 36%, 11%, and 0%, respectively; the annual hemorrhage risk after
      radiosurgery was 1.1%, and the AVM-related mortality rate was 1.5%. Elderly age
      was not significantly associated with AVM obliteration, radiation-induced
      changes, or hemorrhage after radiosurgery. CONCLUSIONS: Advanced age does not
      appear to confer appreciably worse AVM radiosurgery outcomes, unlike its negative
      effect on AVM surgical outcomes. Thus, when an AVM warrants treatment,
      radiosurgery may be the preferred treatment for elderly patients.

PMID- 25997798
TI  - Electromagnetic detection of a perfect carpet cloak.
AB  - It has been shown that a spherical invisibility cloak originally proposed by
      Pendry et al. can be electromagnetically detected by shooting a charged particle
      through it, whose underlying mechanism stems from the asymmetry of transformation
      optics applied to motions of photons and charges [PRL 103, 243901 (2009)].
      However, the conceptual three-dimensional invisibility cloak that exactly follows
      specifications of transformation optics is formidably difficult to implement,
      while the simplified cylindrical cloak that has been experimentally realized is
      inherently visible. On the other hand, the recent carpet cloak model has acquired
      remarkable experimental development, including a recently demonstrated full
      parameter carpet cloak without any approximation in the required constitutive
      parameters. In this paper, we numerically investigate the electromagnetic
      radiation from a charged particle passing through a perfect carpet cloak and
      propose an experimentally verifiable model to demonstrate symmetry breaking of
      transformation optics. 

PMID- 25997799
TI  - miR-2861 as novel HDAC5 inhibitor in CHO cells enhances productivity while
      maintaining product quality.
AB  - Histone deacetylase (HDAC) inhibitors have been exploited for years to improve
      recombinant protein expression in mammalian production cells. However, global
      HDAC inhibition is associated with negative effects on various cellular
      processes. microRNAs (miRNAs) have been shown to regulate gene expression in
      almost all eukaryotic cell types by controlling entire cellular pathways. Since
      miRNAs recently have gained much attention as next-generation cell engineering
      tool to improve Chinese hamster ovary (CHO) cell factories, we were interested if
      miRNAs are able to specifically repress HDAC expression in CHO cells to
      circumvent limitations of unspecific HDAC inhibition. We discovered a novel miRNA
      in CHO cells, miR-2861, which was shown to enhance productivity in various
      recombinant CHO cell lines. Furthermore, we demonstrate that miR-2861 might post
      transcriptionally regulate HDAC5 in CHO cells. Intriguingly, siRNA-mediated HDAC5
      suppression could be demonstrated to phenocopy pro-productive effects of miR-2861
      in CHO cells. This supports the notion that miRNA-induced inhibition of HDAC5 may
      contribute to productivity enhancing effects of miR-2861. Furthermore, since
      product quality is fundamental to safety and functionality of biologics, we
      examined the effect of HDAC inhibition on critical product quality attributes. In
      contrast to unspecific HDAC inhibition using VPA, enforced expression of miR-2861
      did not negatively influence antibody aggregation or N-glycosylation. Our
      findings highlight the superiority of miRNA-mediated inhibition of specific HDACs
      and present miR-2861 as novel cell engineering tool for improving CHO
      manufacturing cells.

PMID- 25997800
TI  - How Does a Patient's Primary Renal Disease Impact Chronic Dialysis Management?:
      Diseases Treated with Immunosuppressive Agents.

PMID- 25997801
TI  - Operating theatre ventilation systems and microbial air contamination in total
      joint replacement surgery: results of the GISIO-ISChIA study.
AB  - BACKGROUND: Recent studies have shown a higher rate of surgical site infections
      in hip prosthesis implantation using unidirectional airflow ventilation compared
      with turbulent ventilation. However, these studies did not measure the air
      microbial quality of operating theatres (OTs), and assumed it to be compliant
      with the recommended standards for this ventilation technique. AIM: To evaluate
      airborne microbial contamination in OTs during hip and knee replacement surgery,
      and compare the findings with values recommended for joint replacement surgery.
      METHODS: Air samplings were performed in 28 OTs supplied with unidirectional,
      turbulent and mixed airflow ventilation. Samples were collected using passive
      sampling to determine the index of microbial air contamination (IMA). Active
      sampling was also performed in some of the OTs. The average number of people in
      the OT and the number of door openings during the sampling period were recorded.
      FINDINGS: In total, 1228 elective prosthesis procedures (60.1% hip and 39.9%
      knee) were included in this study. Of passive samplings performed during surgical
      activity in unidirectional airflow ventilation OTs (U-OTs) and mixed airflow OTs
      (M-OTs), 58.9% and 87.6% had IMA values >2, respectively. Of samplings performed
      during surgical activity in turbulent airflow OTs (T-OTs) and in turbulent
      airflow OTs with the surgical team wearing Steri-Shield Turbo Helmets (TH-OTs),
      8.6% and 60% had IMA values <= 2, respectively. Positive correlation was found
      between IMA values and the number of people in the OT and the number of door
      openings (P < 0.001). In addition, correlation was found between active and
      passive sampling (P < 0.001). CONCLUSION: These findings challenge the belief
      that unidirectional systems always provide acceptable airborne bacterial counts.

PMID- 25997802
TI  - Management of patients with suspected infectious diarrhoea in hospitals in
      England.
AB  - BACKGROUND: Advances in molecular and genomic testing for patients with suspected
      infectious diarrhoea are on the horizon. It is important to understand how
      infection control and microbiology departments currently operate with respect to
      the management of these patients in order to assess the implications of more
      widespread diagnostic testing. However, there are few data available on current
      practice in this context. AIM: To describe current infection control and
      microbiologist practice across England with respect to the management of patients
      with suspected infectious diarrhoea. METHODS: Hospitals in England completed
      three questionnaires on current testing practice in this context. Questionnaire
      design was informed by current practice within the Oxford University Hospitals
      group. FINDINGS: Forty-one percent of hospitals completed at least one
      questionnaire. A notable proportion of staff time was devoted to the management
      of patients with suspected infectious diarrhoea. Staff training was generally
      good, but compliance with policy documents was only 80%. Cleaning and isolation
      policies varied across hospitals, suggesting that either these were not evidence
      based, or that the evidence base is weak. There was more agreement on outbreak
      definitions, management, and cohorting policies. Stool-testing decisions were
      mainly driven by patient characteristics, whereas strain typing was infrequently
      used (except to investigate Clostridium difficile infections). Multiple practical
      difficulties associated with patient management were identified, along with a
      clear appetite for more widespread genomic diagnostic testing. CONCLUSION:
      Managing patients with suspected infectious diarrhoea is a major burden in
      England. Advances in testing practice in this context could have significant
      clinical and economic impacts.

PMID- 25997803
TI  - The 'My five moments for hand hygiene' concept for the overcrowded setting in
      resource-limited healthcare systems.
AB  - Hand hygiene is a core activity of patient safety for the prevention of
      healthcare-associated infections (HCAIs). To standardize hand hygiene practices
      globally the World Health Organization (WHO) released Guidelines on Hand Hygiene
      in Health Care and introduced the 'My five moments for hand hygiene' concept to
      define indications for hand hygiene rooted in an evidence-based model for
      transmission of micro-organisms by healthcare workers' (HCWs) hands. Central to
      the concept is the division of the healthcare environment into two geographical
      care zones, the patient zone and the healthcare zone, that requires the HCW to
      comply with specific hand hygiene moments. In resource-limited, overcrowded
      healthcare settings inadequate or no spatial separation between beds occurs
      frequently. These conditions challenge the HCW's ability to visualize and
      delineate patient zones. The 'My five moments for hand hygiene' concept has been
      adapted for these conditions with the aim of assisting hand hygiene educators,
      auditors, and HCWs to minimize ambiguity regarding shared patient zones and
      achieve the ultimate goal set by the WHO Guidelines--the reduction of infectious
      risks.

PMID- 25997804
TI  - Meticillin-resistant Staphylococcus aureus in the intensive care unit: its effect
      on outcome and risk factors for acquisition.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is a common cause
      of nosocomial infection in the intensive care unit (ICU). A perception exists
      that ICU-acquired MRSA is associated with poor outcomes, although there are few
      data to support this. AIM: To determine the effect of acquiring MRSA in the ICU
      on 180-day mortality, and to identify risk factors associated with acquisition.
      METHODS: Data were collected prospectively from 2007 to 2013. Patients who
      remained MRSA negative throughout their ICU admission were matched with patients
      who acquired MRSA in terms of age, Acute Physiology and Chronic Health Evaluation
      II score, length of ICU stay and surgical/non-surgical status. FINDINGS: In
      total, 2405 patients were included in the analysis. Patients who acquired MRSA in
      the ICU had significantly longer ICU stays than patients who were admitted with
      MRSA and patients who remained MRSA negative throughout their ICU stay (P < 0.001
      for both). There were no significant differences in 180-day mortality between the
      groups (P = 0.238). A confirmed non-MRSA infection within 48 h of ICU admission
      was associated with increased risk of MRSA acquisition (adjusted odds ratio 2.57,
      P = 0.005), and receipt of antimicrobial therapy within 48 h of ICU admission was
      associated with reduced risk of MRSA acquisition (adjusted odds ratio 0.38, P =
      0.014). CONCLUSION: MRSA acquisition does not contribute towards mortality in
      critically ill patients. This raises questions regarding the cost-effectiveness
      of focusing infection prevention measures on the control of MRSA in ICUs. The low
      acquisition rate and lack of risk factors identified for MRSA in the study cohort
      indicate that efforts should be directed towards continual improvement of
      standard infection control procedures for all patients.

PMID- 25997805
TI  - Effects of vapocoolant spray on skin sterility prior to intravenous cannulation.
AB  - BACKGROUND: Alkane vapocoolant sprays evaporate rapidly, lower skin temperature
      and result in a temporary interruption in pain sensation. They reduce the pain of
      intravenous cannulation. However, concern exists that they may recontaminate the
      sterile cannulation site. AIM: To determine the effects of vapocoolant spray on
      skin sterility prior to cannulation. METHODS: Fifty patients from the emergency
      department of a large tertiary metropolitan hospital were enrolled in this study.
      Bacterial skin swabs were taken from the dorsum of both hands of each patient.
      From one hand, a swab was taken following standard chlorhexidine disinfection,
      and a second swab was taken following the application of vapocoolant spray. From
      the other hand, a swab was taken from unprepared (non-disinfected) skin, and a
      second swab was taken following vapocoolant application. Skin swabs were sent for
      microbiological culture and quantitative comparison. FINDINGS: The administration
      of vapocoolant after skin disinfection did not increase the bacterial colony
      count significantly: median 0.0 [interquartile range (IQR) 0.0] vs 0.0 (IQR 0.0)
      (P = 0.71). The administration of vapocoolant to the unprepared skin decreased
      the colony count significantly: median 33.5 (IQR 68) vs 3.0 (IQR 11) (P < 0.001).
      CONCLUSION: Alkane vapocoolant spray does not recontaminate the skin after
      disinfection, and should pose no increased risk of infection when used as an
      anaesthetic agent prior to intravenous cannulation following disinfection. While
      it does have inherent bactericidal activity, this is not sufficient for it to be
      used as the sole disinfectant.

PMID- 25997806
TI  - The Prevalence and Biochemical Profiles of EDTA-Dependent Pseudothrombocytopenia
      in a Generally Healthy Population.

PMID- 25997807
TI  - Optimization of iterative reconstruction parameters with 3-dimensional resolution
      recovery, scatter and attenuation correction in 123I-FP-CIT SPECT.
AB  - OBJECTIVE: The aim of this study was to determine the optimal reconstruction
      parameters on ordered-subset expectation maximization iterative reconstruction
      with resolution recovery, scatter and attenuation correction (OSEM(RRSCAC)) on
      (123)I-FP-CIT SPECT in terms of the image quality, quantification and diagnostic
      ability. METHODS: We evaluated the quality and quantification in (123)I-FP-CIT
      SPECT images obtained by different reconstruction parameters using the
      anthropomorphic striatal phantom. The phantom images were acquired using a
      SPECT/CT system equipped with a low- and medium-energy general-purpose collimator
      and then were reconstructed using OSEM(RRSCAC) with various update numbers and
      the full width at half maximum (FWHM) of the Gaussian filter. The count ratio of
      the striatum, the coefficient of variation (CV) on the background and the
      specific binding ratio (SBR) were calculated to determine the optimal
      reconstruction parameters. Then, 42 consecutive patients who underwent (123)I-FP
      CIT SPECT were selected for clinical study. The patients were grouped into
      potentially decreasing group (20 with Parkinson's disease, 5 with parkinsonian
      syndrome and 5 with dementia with Lewy bodies) and potentially normal binding
      group (4 with Alzheimer disease and 8 with essential tremor). Clinical images
      were reconstructed using OSEM(RRSCAC) and FBP with Chang's AC (FBP(AC)). The
      performance of OSEM(RRSCAC) with the optimal reconstruction parameters was
      evaluated according to the receiver operating characteristic analysis and visual
      assessment. RESULTS: The count ratio increased with an increasing update number
      and converged uniformly with an update number over 90. The CV continuously
      increased with the update number. The SBR also increased with an increasing
      update number and converged uniformly with an update number of 90 or larger. The
      FWHM of the Gaussian filter influenced the image quality and quantification. In
      the clinical study, the area under curve (AUC) for the OSEM(RRSCAC) and FBP(AC)
      were 0.9812 and 0.9759, respectively. The quality of the SPECT images of
      OSEM(RRSCAC) (3.8 +/- 0.8) was significantly superior to that of FBP(AC) (2.2 +/-
      0.7). CONCLUSIONS: We determined that the optimal reconstruction parameter for
      OSEM(RRSCAC) was 90 update numbers with 6.6 mm FWHM of the Gaussian filter. Our
      results suggested that the optimal reconstruction parameters have a potential to
      improve the performance and the image quality of (123)I-FP-CIT SPECT in
      comparison with the FBP reconstruction.

PMID- 25997808
TI  - Dynamics of bacterial assemblages and removal of polycyclic aromatic hydrocarbons
      in oil-contaminated coastal marine sediments subjected to contrasted oxygen
      regimes.
AB  - To study the impact of oxygen regimes on the removal of polycylic aromatic
      hydrocarbons (PAHs) in oil-spill-affected coastal marine sediments, we used a
      thin-layer incubation method to ensure that the incubated sediment was fully
      oxic, anoxic, or was influenced by oxic-anoxic switches without sediment
      stirring. Hydrocarbon content and microbial assemblages were followed during 60
      days to determine PAH degradation kinetics and microbial community dynamics
      according to the oxygenation regimes. The highest PAH removal, with 69 %
      reduction, was obtained at the end of the experiment under oxic conditions,
      whereas weaker removals were obtained under oscillating and anoxic conditions (18
      and 12 %, respectively). Bacterial community structure during the experiment was
      determined using a dual 16S rRNA genes/16S rRNA transcripts approach, allowing
      the characterization of metabolically active bacteria responsible for the
      functioning of the bacterial community in the contaminated sediment. The shift of
      the metabolically active bacterial communities showed that the selection of first
      responders belonged to Pseudomonas spp. and Labrenzia sp. and included an
      unidentified Deltaproteobacteria-irrespective of the oxygen regime-followed by
      the selection of late responders adapted to the oxygen regime. A novel
      unaffiliated phylotype (B38) was highly active during the last stage of the
      experiment, at which time, the low-molecular-weight (LMW) PAH biodegradation
      rates were significant for permanent oxic- and oxygen-oscillating conditions,
      suggesting that this novel phylotype plays an active role during the restoration
      phase of the studied ecosystem.

PMID- 25997810
TI  - Effects of electrolysis by low-amperage electric current on the chlorophyll
      fluorescence characteristics of Microcystis aeruginosa.
AB  - Effects of electrolysis by low-amperage electric current on the chlorophyll
      fluorescence characteristics of Microcystis aeruginosa were investigated in order
      to reveal the mechanisms of electrolytic inhibition of algae. Threshold of
      current density was found under a certain initial no. of algae cell. When current
      density was equal to or higher than the threshold (fixed electrolysis time),
      growth of algae was inhibited completely and the algae lost the ability to
      survive. Effect of algal solution volume on algal inhibition was insignificant.
      Thresholds of current density were 8, 10, 14, 20, and 22 mA cm(-2) at 2.5 *
      10(7), 5 * 10(7), 1 * 10(8), 2.5 * 10(8), and 5 * 10(8) cells mL(-1) initial no.
      of algae cell, respectively. Correlativity between threshold of current and
      initial no. of algae cells was established for scale-up and determining operating
      conditions. Changes of chlorophyll fluorescence parameters demonstrated that
      photosystem (PS) II of algae was damaged by electrolysis but still maintained
      relatively high activity when algal solution was treated by current densities
      lower than the threshold. The activity of algae recovered completely after 6 days
      of cultivation. On the contrary, when current density was higher than the
      threshold, connection of phycobilisome (PBS) and PS II core complexes was
      destroyed, PS II system of algae was damaged irreversibly, and algae could not
      survive thoroughly. The inactivation of M. aeruginosa by electrolysis can be
      attributed to irreversible separation of PBS from PS II core complexes and the
      damage of PS II of M. aeruginosa.

PMID- 25997809
TI  - Humic acids enhance the microbially mediated release of sedimentary ferrous iron.
AB  - Iron (Fe) is an essential element for many organisms, but high concentrations of
      iron can be toxic. The complex relation between iron, arsenic (As), bacteria, and
      organic matter in sediments and groundwater is still an issue of environmental
      concern. The present study addresses the effects of humic acids and
      microorganisms on the mobilization of iron in sediments from an arsenic-affected
      area, and the microbial diversity was analyzed. The results showed that the
      addition of 50, 100, and 500 mg/L humic acids enhanced ferrous iron (Fe(II))
      release in a time-dependent and dose-dependent fashion under anaerobic
      conditions. A significant increase in the soluble Fe(II) concentrations occurred
      in the aqueous phases of the samples during the first 2 weeks, and aqueous Fe(II)
      reached its maximum concentrations after 8 weeks at the following Fe(II)
      concentrations: 28.95 +/- 1.16 mg/L (original non-sterilized sediments), 32.50 +/
      0.71 mg/L (50 mg/L humic acid-amended, non-sterilized sediments), 37.50 +/- 1.85
      mg/L (100 mg/L humic acid-amended, non-sterilized sediments), and 39.00 +/- 0.43
      mg/L (500 mg/L humic acid-amended, non-sterilized sediments). These results
      suggest that humic acids can further enhance the microbially mediated release of
      sedimentary iron under anaerobic conditions. By contrast, very insignificant
      amounts of iron release were observed from sterilized sediments (the abiotic
      controls), even with the supplementation of humic acids under anaerobic
      incubation. In addition, the As(III) release was increased from 50 +/- 10 MUg/L
      (original non-sterilized sediments) to 110 +/- 45 MUg/L (100 mg/L humic acid
      amended, non-sterilized sediments) after 8 weeks of anaerobic incubation.
      Furthermore, a microbial community analysis indicated that the predominant class
      was changed from Alphaproteobacteria to Deltaproteobacteria, and clearly
      increased populations of Geobacter sp., Paludibacter sp., and Methylophaga sp.
      were found after adding humic acids along with the increased release of iron and
      arsenic. Our findings provide evidence that humic acids can enhance the
      microbially mediated release of sedimentary ferrous iron in an arsenic-affected
      area. It is thus suggested that the control of anthropogenic humic acid use and
      entry into the environment is important for preventing the subsequent iron
      contamination in groundwater.

PMID- 25997812
TI  - Return to recreational sports activity after anterior cruciate ligament
      reconstruction: a one- to six-year follow-up study.
AB  - INTRODUCTION: The aim of this study was to evaluate mid-term return to
      recreational sport in general population and identify factors related with sports
      return. METHODS: Retrospective evaluation of 99 recreational sports players
      (Tegner score of 6) with ACL arthroscopic reconstructions with hamstring
      autograft, between 2006-2011. 74 male and 25 female with middle age of 30 years
      (14-52). We made a questionnaire focused on sports level before injury and after
      surgery, and different scales: Lysholm, Tegner Activity Level, IKDC and a Likert
      scale for quantify their motivation for return to sports. RESULTS: With a medium
      follow-up of 36 months, 90 patients (91.9 %) had returned to recreational sport.
      51 (51.52 %) had returned to sports at the same level, and these are those with
      lower BMI (average 23), higher IKDC and Lysholm scores (p < 0.01) and also they
      believe that sport is an important activity. Only 9 % of patients left sports.
      They were principally male athletes (88 %), with higher medium age (32), lesser
      time between injury and surgery (22 months), higher BMI (26), in comparison with
      athletes that return to sports. CONCLUSIONS: The results suggest good mid-term
      return to recreational sports in general population. The following factors had a
      statistically significant influence on the return to sports activity: type of
      sport, sex and functional state of the operated knee (IKDC-Lysholm).
      Psychological and social factors may have a fundamental influence on return to
      sports activity.

PMID- 25997811
TI  - Antimony-doped graphene nanoplatelets.
AB  - Heteroatom doping into the graphitic frameworks have been intensively studied for
      the development of metal-free electrocatalysts. However, the choice of
      heteroatoms is limited to non-metallic elements and heteroatom-doped graphitic
      materials do not satisfy commercial demands in terms of cost and stability. Here
      we realize doping semimetal antimony (Sb) at the edges of graphene nanoplatelets
      (GnPs) via a simple mechanochemical reaction between pristine graphite and solid
      Sb. The covalent bonding of the metalloid Sb with the graphitic carbon is
      visualized using atomic-resolution transmission electron microscopy. The Sb-doped
      GnPs display zero loss of electrocatalytic activity for oxygen reduction reaction
      even after 100,000 cycles. Density functional theory calculations indicate that
      the multiple oxidation states (Sb(3+) and Sb(5+)) of Sb are responsible for the
      unusual electrochemical stability. Sb-doped GnPs may provide new insights and
      practical methods for designing stable carbon-based electrocatalysts. 

PMID- 25997813
TI  - Dapagliflozin-induced weight loss affects 24-week glycated haemoglobin and blood
      pressure levels.
AB  - The aim of this study was to investigate the associations between dapagliflozin
      mediated reductions in body weight and reductions in glycated haemoglobin (HbA1c)
      and blood pressure. Data were pooled from seven studies evaluating dapagliflozin
      10 mg as monotherapy or combination therapy over 24 weeks. Using linear
      regression to estimate the contribution of weight loss to HbA1c and blood
      pressure reductions, the beta-value estimate for HbA1c (%)/kg was 0.028 (p <
      0.0001). Weight loss of 2 kg with dapagliflozin contributed to 6% of the total
      HbA1c reduction. For systolic (SBP) and diastolic blood pressure (DBP), the beta
      value (mmHg/kg) estimates were 0.606 (p < 0.0001) and 0.253 (p < 0.0001),
      respectively. Weight loss of 2 kg contributed to 28% of the overall SBP
      reduction, and 24% of the overall DBP reduction. In conclusion, dapagliflozin
      mediated weight loss may contribute to overall reductions in HbA1c and blood
      pressure. 

PMID- 25997814
TI  - Auditory brainstem responses to CE-Chirp(r) stimuli for normal ears and those
      with sensorineural hearing loss.
AB  - OBJECTIVE: Evaluation of the characteristic differences between click-and CE
      Chirp-evoked auditory brainstem responses (ABRs) in normal hearing and
      sensorineural hearing loss. DESIGN: A prospective study. Ears with normal hearing
      and with sensorineural hearing loss were evaluated. Pure-tone audiometry and
      click-and CE-Chirp evoked ABRs exams were conducted for all ears. Visual
      detection levels, wave-V amplitudes, and latencies of the ABRs were assessed.
      STUDY SAMPLE: Twenty-two ears with normal hearing and 22 ears with sloping type
      sensorineural hearing loss were examined. RESULTS: In normal-hearing ears, mean
      amplitudes were larger for CE-chirps than for clicks at all intensities until 80
      dB nHL, at which the amplitudes dropped off, presumably due to upward spread of
      excitation. In ears with sensorineural hearing loss, however the drop-off was
      less significant at 80 dB nHL. Comparisons with pure-tone audiometry findings
      revealed ABRs to CE-Chirps to correlate at 0.5, 1, 2, and 3 kHz, and to clicks at
      1, 2, 3, and 4 kHz. CONCLUSIONS: The CE-Chirp has advantages over clicks for
      examining normal ears. However, under high-level stimulation, these advantages
      are no longer present. In ears with sensorineural hearing loss, the upward spread
      of excitation is less prominent. The CE-Chirps results correlate significantly to
      low frequency audiometric findings at 0.5 kHz, while clicks do not.

PMID- 25997815
TI  - Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with
      metastatic gastric cancer.
AB  - BACKGROUND: Although the docetaxel, 5-fluorouracil, and cisplatin triplet has
      yielded significant improvements in time to progression, overall survival, and
      overall response rate, the high incidence of severe adverse events limits the use
      of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this
      limitation, we evaluated the efficacy and safety of the combination of docetaxel,
      oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. METHODS:
      Chemotherapy-naive patients with pathologically proven unresectable recurrent or
      metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at
      52.5 mg/m(2) and oxaliplatin at 105 mg/m(2) were administered intravenously on
      day 1, and S-1 was administered orally at 80 mg/m(2) on days 1-14 of every 21-day
      cycle. RESULTS: Forty-four patients (median age 54.5 years) were enrolled. All
      patients had metastatic disease. A total of 340 cycles of chemotherapy were
      administered (median of eight cycles per patient; range 1-36 cycles). Toxicities
      were evaluated in 43 patients, and the responses were evaluated in 40 patients.
      Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %).
      The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %]
      in the intention-to-treat population. The median progression-free survival and
      overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 %
      CI 6.9-17.2 months), respectively. CONCLUSION: These data suggest that the
      docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively
      well tolerable, and it seems to have potential to be a reasonable therapeutic
      strategy in patients with metastatic or recurrent gastric cancer.

PMID- 25997816
TI  - Osteoporosis and Aortic Stenosis: 'Killing Two Birds with One Stone'?

PMID- 25997817
TI  - The first study published?

PMID- 25997819
TI  - MicroRNA-29a inhibits cell migration and invasion via targeting Roundabout
      homolog 1 in gastric cancer cells.
AB  - Deregulation of Roundabout homolog 1 (Robo1) has been demonstrated to be
      associated with several types of human cancer, including gastric cancer. However,
      the detailed role of Robo1 and its regulatory mechanism in gastric cancer remain
      largely unclear. In the current study, it was demonstrated that the expression of
      microRNA (miR)-29a was frequently reduced in gastric cancer tissues, compared
      with their matched normal adjacent tissues. Similar results were additionally
      observed in AGS and SGC-7901 human gastric cancer cells. Overexpression of miR
      29a led to reduced migration and invasion of AGS cells. To explore the targets of
      miR-29a in gastric cancer, bioinformatics analysis was conducted and Robo1 was
      identified as a putative target of miR-29a. Further western blotting and
      luciferase activity assay data confirmed that miR-29a was able to negatively
      regulate the protein expression of Robo1, through directly binding to the 3'
      untranslated region of Robo1 mRNA in gastric cancer cells. In addition, it was
      demonstrated that Robo1 was frequently upregulated in gastric cancer tissues
      compared with their matched adjacent normal tissues, and a significant inverse
      correlation was identified between miR-29a and Robo1 expression. In addition,
      knockdown of Robo1 by small interfering RNA markedly inhibited the migratory and
      invasive capabilities of AGS cells, which the results obtained with
      overexpression of miR-29a. In conclusion, to the best of our knowledge the
      current study suggested for the first time, that miR-29a inhibits migration and
      invasion in part via direct inhibition of Robo1 in gastric cancer cells.
      Therefore, Robo1 and miR-29a may serve as diagnostic or therapeutic targets for
      gastric cancer.

PMID- 25997818
TI  - A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in
      combination with docetaxel in second-line therapy of advanced non-small cell lung
      cancer (GALAXY-1).
AB  - BACKGROUND: This trial was designed to evaluate the activity and safety of
      ganetespib in combination with docetaxel in advanced non-small cell lung cancer
      (NSCLC) and to identify patient populations most likely to benefit from the
      combination. PATIENTS AND METHODS: Patients with one prior systemic therapy for
      advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered
      alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The
      primary end points were progression-free survival (PFS) in two subgroups of the
      adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH)
      and mutated KRAS (mKRAS). RESULTS: Of 385 patients enrolled, 381 were treated.
      Early in the trial, increased hemoptysis and lack of efficacy were observed in
      nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma
      histology were subsequently enrolled. Neutropenia was the most common grade >=3
      adverse event: 41% in the combination arm versus 42% in docetaxel alone. There
      was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted
      hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P =
      0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a
      trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P =
      0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory
      analyses showed significant benefit of the ganetespib combination in the
      prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease
      >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS
      (adjusted HR = 0.69, P = 0.0191). CONCLUSION: Advanced lung adenocarcinoma
      patients treated with ganetespib in combination with docetaxel had an acceptable
      safety profile. While the study's primary end points were not met, significant
      prolongation of PFS and OS was observed in patients >6 months from diagnosis of
      advanced disease, a subgroup chosen as the target population for the phase III
      study.

PMID- 25997820
TI  - The proto-oncogene survivin splice variant 2B is induced by PDGF and leads to
      cell proliferation in rheumatoid arthritis fibroblast-like synoviocytes.
AB  - Survivin is an independent prognostic factor for joint destruction in rheumatoid
      arthritis (RA). However, the expression and function of survivin in RA
      synoviocytes remain unclear. We certified the expression of survivin in RA
      synovial tissues and performed the experiment using RA fibroblast-like
      synoviocytes (RA-FLS) treated with siRNA. As a result, the expression levels of
      wild type (WT) survivin and the 2B splice variants in RA synovial tissues were
      higher than those in osteoarthritis tissue samples, and, these variants were
      highly expressed in RA-FLS. The expression levels of survivin-WT and -2B in the
      RA-FLS were upregulated by PDGF. Treatment with siRNA against survivin-2B led to
      decreased viability of PDGF-treated RA-FLS due to cell cycle suppression and
      apoptosis promotion, while the siRNA against all survivin isoforms did not affect
      the viability. Moreover, an overexpression of survivin-2B in RA-FLS led to cell
      proliferation through cell cycle activation and by conferring resistance to
      apoptosis. In conclusion, survivin-2B has an important role in RA-FLS
      proliferation. These data suggest that survivin-2B might contribute to rheumatoid
      synovial hyperplasia, and have the potential as a novel therapeutic target for
      RA. 

PMID- 25997821
TI  - Spironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of
      mineralocorticoid-induced hypertensive rats.
AB  - INTRODUCTION: Aldosterone can induce changes in the expression or activity of
      Na(+)/H(+) exchanger isoform 1 (NHE-1) in vascular smooth muscle cells. We aimed
      to clarify whether chronic mineralocorticoid receptor activation exerts an effect
      on the activity of NHE-1 in the aorta of mineralocorticoid-induced hypertensive
      rats. METHODS: Uninephrectomized male Sprague-Dawley rats received subcutaneously
      10 mg/week of desoxycorticosterone (DOCA) with or without 20 mg/kg of
      spironolactone, or vehicle alone (n = 20). After four weeks of treatment, the
      animals were sacrificed; the aorta was excised for subsequent studies, including
      histological analysis, RT-PCR, Western blot, measurement of NHE-1 activity and
      vascular contractility in the presence or absence of the selective NHE-1
      inhibitor ethyl-isopropyl amiloride (EIPA). RESULTS: Chronic DOCA treatment
      increased the NHE-1 activity, systolic and diastolic blood pressure, and aortic
      wall thickness. All these effects were prevented by co-treatment with
      Spironolactone (p < 0.05). Phenylephrine-induced vascular contractility was
      significantly reduced in the DOCA group when EIPA was added in the media (p <
      0.05). No significant differences in NHE-1 mRNA or protein levels were detected
      between groups. CONCLUSIONS: Chronic DOCA administration induced functional and
      morphological alterations in the rat aorta that are partially explained by
      enhanced NHE-1 activity and prevented by spironolactone. However, we did not
      observe changes in the NHE-1 transcript or protein levels, suggesting that the
      effect may be due to post-transcriptional modifications induced by
      mineralocorticoid receptor activation.

PMID- 25997822
TI  - The oxidative damage to the human telomere: effects of 5-hydroxymethyl-2'
      deoxyuridine on telomeric G-quadruplex structures.
AB  - As part of the genome, human telomeric regions can be damaged by the chemically
      reactive molecules responsible for oxidative DNA damage. Considering that G
      quadruplex structures have been proven to occur in human telomere regions,
      several studies have been devoted to investigating the effect of oxidation
      products on the properties of these structures. However only investigations
      concerning the presence in G-quadruplexes of the main oxidation products of
      deoxyguanosine and deoxyadenosine have appeared in the literature. Here, we
      investigated the effects of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU), one of the
      main oxidation products of T, on the physical-chemical properties of the G
      quadruplex structures formed by two human telomeric sequences. Collected
      calorimetric, circular dichroism and electrophoretic data suggest that, in
      contrast to most of the results on other damage, the replacement of a T with a 5
      hmdU results in only negligible effects on structural stability. Reported results
      and other data from literature suggest a possible protecting effect of the loop
      residues on the other parts of the G-quadruplexes. 

PMID- 25997823
TI  - Sugar Derivatives of Morphine: A New Window for the Development of Potent
      Anesthetic Drugs.
AB  - This review provides a short account of carbohydrate derivatives of an important
      natural drug, morphine, along with their comparative efficacies as anesthetic
      agent. Sugar derivatives are found to have more prospect as anesthetic drug than
      morphine itself owing to their enhanced bioavailability. Synthetic schemes of
      these sugar derivatives and information on related patents are also included in
      this manuscript. 

PMID- 25997825
TI  - Specific IgG and immune complex responses to parthenogenetic females and eggs of
      nematode Strongyloides venezuelensis for the diagnosis of immunosuppression in
      infected rats.
AB  - In the present study, antigens from parthenogenetic females and eggs of
      Strongyloides venezuelensis, or anti-parthenogenetic-female and anti-egg antigens
      were used to detect specific IgG and immune complex responses, respectively.
      Serum samples from experimentally infected immunocompetent and immunosuppressed
      rats were analysed on days 5, 8, 13 and 21 post-infection (dpi). An enzyme-linked
      immunosorbent assay (ELISA) was performed using alkaline parasite extract for
      specific IgG detection, and anti-parthenogenetic-female or anti-egg antigens for
      immune complex detection. The data were analysed using analysis of variance
      (ANOVA), followed by a Bonferroni test. When parthenogenetic female or egg
      extracts were used as antigens, specific IgGs were not detected in either
      immunocompetent or immunosuppressed rats. When anti-parthenogenetic-female or
      anti-S. venezuelensis-eggs were used, immune complexes were detected for the
      duration of the infection in immunosuppressed animals and were only detected
      between 5 and 13 dpi in immunocompetent animals. The duration of infection was
      not significantly different between the immunocompetent and immunosuppressed
      groups when anti-parthenogenetic-female or anti-S. venezuelensis-eggs were used.
      Parthenogenetic female extracts yielded significant differences between antibody
      and immune complex responses in immunocompetent rats from 5 to 13 dpi, but only
      on day 5 dpi in immunosuppressed rats. Exposure to S. venezuelensis egg extract
      yielded significant differences in both antibody and immune complex detection
      between immunocompetent and immunosuppressed rats for the duration of the
      infection. In conclusion, ELISA using alternative antigens may be a successful
      strategy for identifying immune complexes in serum samples and diagnosing active
      strongyloidiasis, particularly under conditions of immunosuppression. 

PMID- 25997826
TI  - Inflammation and oxidative stress, rather than hypoxia, are predominant factors
      promoting angiogenesis in the initial phases of atherosclerosis.
AB  - Micro-angiogenesis in the arterial wall has been observed during the development
      and progression of atherosclerosis. The aim of the present study was to examine
      whether inflammation, oxidative stress and hypoxia are involved in the process of
      early atherosclerotic micro-angiogenesis. A total of 24 rabbits were randomly
      divided into a normal diet group or a high-cholesterol (HC) diet group and were
      fed the corresponding diets for 4 weeks. The microvessel density (MVD), level of
      hypoxia and the levels of inflammatory markers and antioxidants in the arterial
      wall were detected using immunohistochemical and molecular biological techniques,
      respectively. The present results demonstrated that the MVD in the HC group was
      significantly higher (P<0.01) than that observed in the rabbits, which were
      provided with a normal diet, while hypoxia-inducible factor-1alpha levels did not
      exhibit marked changes in either of the two groups (P>0.05). The levels of
      inflammatory markers and antioxidants were significantly different between the
      two groups (P<0.05). The present study demonstrated that the primary factors,
      which promote micro-angiogenesis are possibly associated with an increase in
      inflammation and a decrease in the levels of antioxidants, as tissue hypoxia in
      the arterial wall at this stage was not evident. 

PMID- 25997827
TI  - Perioperative local infiltration anesthesia with ropivacaine has no effect on
      postoperative pain after total hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: The local infiltration analgesia (LIA) technique has been
      widely used to reduce opioid requirements and to improve postoperative
      mobilization following total hip arthroplasty (THA). However, the evidence for
      the efficacy of LIA in THA is not yet clear. We determined whether single-shot
      LIA in addition to a multimodal analgesic regimen would reduce acute
      postoperative pain and opioid requirements after THA. PATIENTS AND METHODS: 116
      patients undergoing primary THA under spinal anesthesia were included in this
      randomized, double-blind, placebo-controlled trial. All patients received oral
      opioid-sparing multimodal analgesia: etoricoxib, acetaminophen, and
      glucocorticoid. The patients were randomized to receive either 150 mL ropivacaine
      (2 mg/mL) and 0.5 mL epinephrine (1 mg/mL) or 150 mL 0.9% saline. Rescue
      analgesic consisted of morphine and oxycodone as needed. The primary endpoint was
      pain during mobilization in the recovery unit. Secondary endpoints were pain
      during mobilization on the day after surgery and total postoperative opioid
      requirements on the first postoperative day. RESULTS: The levels of pain during
      mobilization-both in the recovery unit and on the day after surgery-and
      consumption of opioids on the first postoperative day were similar in the 2
      groups. INTERPRETATION: LIA did not provide any extra analgesic effect after THA
      over and above that from the multimodal analgesic regimen used in this study.

PMID- 25997828
TI  - RON alternative splicing regulation in primary ovarian cancer.
AB  - The proto-oncogene recepteur d'origine nantais (RON, MST1R) and its alternatively
      spliced variants are involved in various tumor biological processes, such as cell
      motility, adhesion, proliferation, apoptosis and epithelial-to-mesenchymal
      transition (EMT). RON overexpression and the occurrence of specific alternatively
      spliced RON isoforms have been detected in ovarian cancer. In the present study,
      we evaluated the role and regulation of cancer-related RON splicing isoforms in
      primary ovarian cancer. Expression of RON variants (RONDelta165, RONDelta160) was
      determined in 45 primary ovarian cancer and 4 physiological ovarian tissue
      specimens by RT-PCR and western blot analysis. The results were correlated to
      clinicopathological parameters. Additionally, expression of splicing factors with
      known involvement in RON alternative splicing regulation was examined. Increased
      RON levels were detected in all tumor samples (p=0.001) without differences
      between the primary tumors and metastases. Alternative RON variants were present
      in the majority of tumor samples (39 of 45; 86.67%). Potential RONDelta165
      occurred more often (82.22%) than potential RONDelta160 or RONDelta155 (24.40%).
      Several significant correlations of RON and splicing factor expression [e.g.
      ASF/SFRS1 (p=0.035)] were detected. Correlations of RON expression to
      clinicopathological parameters were not observed. Significant splicing factor
      interactions (e.g. SRp55/SRp75: p<0.001) were observed in tumor samples with
      alternative RON splicing. Our data demonstrated upregulated RON isoform
      expression and significant changes in splicing factor expression in primary
      ovarian cancer. These findings account for an essential regulatory interplay of
      splicing factor-driven alterations in the RON alternative splicing pattern with
      subsequent tumor biological consequences in ovarian cancer. 

PMID- 25997829
TI  - Drowning--the preventable killer.

PMID- 25997830
TI  - High Rate of Multidrug-Resistant Gram-Negative Bacilli Carriage and Infection in
      Hospitalized Returning Travelers: A Cross-Sectional Cohort Study.
AB  - BACKGROUND: Carriage of and infection with multidrug-resistant Gram-negative
      bacilli (MDR-GNB) are a potential cause of concern in travelers with no history
      of hospitalization abroad. METHODS: All consecutive returning travelers
      hospitalized in our department between February 2012 and January 2013 were
      prospectively screened for MDR-GNB gastrointestinal tract carriage or infection.
      We compared the prevalence of MDR-GNB in travelers to a non-travelers nonexposed
      group. Then among the travelers, MDR-GNB carriers were compared to noncarriers to
      determine risk factors of acquisition of MDR-GNB. RESULTS: Overall, 359 patients
      (191 travelers, 168 non-travelers) were included, and 25 (6.4%), including 23
      travelers, harbored MDR-GNB. Five travelers had an MDR-GNB infection while 18
      were asymptomatic enteric carriers. MDR-GNB carriage or infection was
      significantly more frequent in travelers (11.0% vs 1.2% for non-travelers, odds
      ratio (OR) = 11.3, p < 0.001) and in patients born outside France (OR = 1.67; p =
      0.03). Among travelers, in multivariate analysis, factors independently
      associated with MDR-GNB carriage or infection were traveling to Asia (OR = 3.1; p
      = 0.01) and visiting friends and relatives (VFR) or migrants (OR=3.6; p = 0.01).
      CONCLUSIONS: The 10-fold higher prevalence rate of MDR-GNB in travelers raises
      the issues of systematic screening of all travelers, and of the choice of first
      line antibiotic therapy when treating urinary tract infections in travelers,
      especially those VFR, migrants, and those returning from Asia.

PMID- 25997831
TI  - The oxygenase Jmjd6--a case study in conflicting assignments.
AB  - The Jumonji domain-containing protein 6 (Jmjd6) is a member of the superfamily of
      non-haem iron(II) and 2-oxoglutarate (2OG)-dependent oxygenases; it plays an
      important developmental role in higher animals. Jmjd6 was initially assigned a
      role as the phosphatidylserine receptor responsible for engulfment of apoptotic
      cells but this now seems unlikely. Jmjd6 has been shown to be a nuclear localized
      protein with a JmjC domain comprising a distorted double-stranded beta-helical
      structure characteristic of the 2OG-dependent oxygenases. Jmjd6 was subsequently
      assigned a role in catalysing N-methyl-arginine residue demethylation on the N
      terminus of the human histones H3 and H4; however, this function is also subject
      to conflicting reports. Jmjd6 does catalyse 2OG-dependent C-5 hydroxylation of
      lysine residues in mRNA splicing-regulatory proteins and histones; there is also
      accumulating evidence that Jmjd6 plays a role in splicing (potentially in an iron
      and oxygen-dependent manner) as well as in other processes regulating gene
      expression, including transcriptional pause release. Moreover, a link with tumour
      progression has been suggested. In the present review we look at biochemical,
      structural and cellular work on Jmjd6, highlighting areas of controversy and
      consensus. 

PMID- 25997832
TI  - Akt/PKB: one kinase, many modifications.
AB  - Akt/PKB, a serine/threonine kinase member of the AGC family of proteins, is
      involved in the regulation of a plethora of cellular processes triggered by a
      wide diversity of extracellular signals and is thus considered a key signalling
      molecule in higher eukaryotes. Deregulation of Akt signalling is associated with
      a variety of human diseases, revealing Akt-dependent pathways as an attractive
      target for therapeutic intervention. Since its discovery in the early 1990s, a
      large body of work has focused on Akt phosphorylation of two residues, Thr308 and
      Ser473, and modification of these two sites has been established as being
      equivalent to Akt activation. More recently, Akt has been identified as a
      substrate for many different post-translational modifications, including not only
      phosphorylation of other residues, but also acetylation, glycosylation,
      oxidation, ubiquitination and SUMOylation. These modifications could provide
      additional regulatory steps for fine-tuning Akt function, Akt trafficking within
      the cell and/or for determining the substrate specificity of this signalling
      molecule. In the present review, we provide an overview of these different post
      translational modifications identified for Akt, focusing on their consequences
      for this kinase activity. 

PMID- 25997833
TI  - Production of gamma-aminobutyric acid from glucose by introduction of synthetic
      scaffolds between isocitrate dehydrogenase, glutamate synthase and glutamate
      decarboxylase in recombinant Escherichia coli.
AB  - Escherichia coli were engineered for the direct production of gamma-aminobutyric
      acid from glucose by introduction of synthetic protein scaffold. In this study,
      three enzymes consisting GABA pathway (isocitrate dehydrogenase, glutamate
      synthase and glutamate decarboxylase) were connected via synthetic protein
      scaffold. By introduction of scaffold, 0.92g/L of GABA was produced from 10g/L of
      glucose while no GABA was produced in wild type E. coli. The optimum pH and
      temperature for GABA production were 4.5 and 30 degrees C, respectively. When
      competing metabolic network was inactivated by knockout mutation, maximum GABA
      concentration of 1.3g/L was obtained from 10g/L glucose. The recombinant E. coli
      strain which produces GABA directly from glucose was successfully constructed by
      introduction of protein scaffold. 

PMID- 25997835
TI  - Vaccine Adjuvants Confer an Advantage to the Kinetics of Activation of Follicular
      Dendritic Cells that are Sensitive to Peripheral Tissue's Injury.

PMID- 25997834
TI  - Berberis libanotica extract targets NF-kappaB/COX-2, PI3K/Akt and
      mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis.
AB  - The aim of this study was to describe and understand the relationship between
      cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells
      after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this
      goal we used erythroleukemia cell lines expressing COX-2 (HEL cell line) or not
      (K562 cell line). Moreover, we made use of COX-2 cDNA to overexpress COX-2 in
      K562 cells. In light of the reported chemopreventive and chemosensitive effects
      of natural products on various tumor cells and animal models, we postulated that
      our Bl extract may mediate their effects through apoptosis induction with
      suppression of cell survival pathways. Our study is the first report on the
      specific examination of intrinsic apoptosis and Akt/NF-kappaB/COX-2 pathways in
      human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced
      apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl
      extract treatment on K562 cells was observed resulting in activation of the late
      markers of apoptosis with caspase-3 activation, PARP cleavage and DNA
      fragmentation. Whereas, we showed that Bl extract reduced significantly
      expression of COX-2 by a dose-dependent manner in HEL and K562 (COX-2+) cells.
      Furthermore, in regard to our results, it is clear that the simultaneous
      inhibition of Akt and NF-kappaB signalling can significantly contribute to the
      anticancer effects of Bl extract in human erythroleukemia cells. We observed that
      the Bl extract is clearly more active than the berberine alone on the induction
      of DNA fragmentation in human erythro-leukemia cells.

PMID- 25997837
TI  - Ghost Cell Suspensions as Blood Analogue Fluid for Macroscopic Particle Image
      Velocimetry Measurements.
AB  - Spatially resolved measurement of blood flow is of great interest in the
      development of artificial blood-carrying devices such as blood pumps, heart valve
      prostheses, and oxygenators. Particle image velocimetry (PIV) is able to measure
      instantaneous velocity fields in a plane with high accuracy and is being used
      more frequently for the development of such devices. However, as this measurement
      technique is based on optical access, blood flow at physiological hematocrit
      values is difficult to measure due to its low transparency and multiscattering
      properties. So far, only very small dimensions (in the range of 400 MUm) can be
      measured using PIV. A suspension of ghost cells (GCs) offers a higher optical
      transparency than blood while having a similar rheological behavior. In this
      study, a procedure for the production of GC suspensions containing a very low
      intracellular hemoglobin concentration is presented. With the help of multiple
      rounds of controlled cell lysis, the intracellular hemoglobin concentration could
      be decreased to a point where a standard macroscopic PIV measurement was
      possible. A velocity profile of a 44% GC suspension in a circular channel with a
      diameter of 9.5 mm was measured with high spatial resolution. Meanwhile, the
      rheological behavior was found to be comparable with blood.

PMID- 25997838
TI  - [Safety and Efficacy of Etanercept in Rheumatoid Arthritis With End-stage Chronic
      Renal Failure].
AB  - The use of etanercept in rheumatoid arthritis patients with end-stage renal
      failure has not been well reported. We report here the case of 58-years-old
      patient who was treated with 50 mg of etanercept once a week to control the
      activity of her disease. The patient improved after starting the treatement. No
      serious infectious complication or side effects were seen. The follow-up was 18
      months. Our case showed the safety and efficacity of etanercept rheumatoid
      arthritis in patient with end-stage renal failure. 

PMID- 25997839
TI  - Painful ulcers.

PMID- 25997840
TI  - Prosodic Realization of Focus in Bilingual Production of Southern Min and
      Mandarin.
AB  - Previously post-focus compression (PFC) - the lowering of fundamental frequency
      (F0) and intensity of post-focal words to below those of the same words in
      identical sentences with neutral focus - was found in Beijing Mandarin but not in
      Taiwan Southern Min and Taiwan Mandarin. This study investigated whether the
      presence of PFC would vary with age and language use of societal bilinguals of
      Southern Min and Mandarin. Three groups of bilingual speakers of Quanzhou
      Southern Min and Mandarin, age around 20, 40 and 60, were examined for their
      prosodic realization of focus. All the speakers acquired Southern Min first,
      followed by Mandarin in childhood, but the younger speakers used more Mandarin
      than the older speakers. Comparisons of duration, intensity and F0 in focused,
      prefocus and post-focus words indicated that all groups produced Taiwan-like
      focus, i.e., without PFC, in Southern Min, but the youngest group produced
      Beijing-like PFC in Mandarin. These findings reveal that increased language
      experience, such as greater amount of second language (L2) use, correlates with
      increased ability to produce native-like PFC in L2, suggesting that PFC can be
      used as an indicator in assessing L2 speech acquisition.

PMID- 25997841
TI  - Nurses' extended work hours: Patient, nurse and organizational outcomes.
AB  - BACKGROUND: Nursing shortages have been associated with increased nurse workloads
      that may result in work errors, thus impacting patient, nurse and organizational
      outcomes. AIM: To examine for the first time in Thailand nurses' extended work
      hours (working more than 40 h per week) and its relationship to patient, nurse
      and organizational outcomes. METHODS: Using multistage sampling, 1524 registered
      nurses working in 90 hospitals across Thailand completed demographic forms: the
      Nurses' Extended Work Hours Form; the Patient, Nurse, Organizational Outcomes
      Form; the Organizational Productivity Questionnaire and the Maslach Burnout
      Inventory. The data were analysed using descriptive statistics, Spearman's rank
      correlation and logistic regression. RESULTS: The average extended work hour of
      respondents was 18.82 h per week. About 80% worked two consecutive shifts. The
      extended work hours had a positive correlation with patient outcomes, such as
      patient identification errors, pressure ulcers, communication errors and patient
      complaints and with nurse outcomes of emotional exhaustion and depersonalization.
      Furthermore, we found a negative correlation between extended work hours and job
      satisfaction as a whole, intent to stay and organizational productivity. Nurses
      who had extended work hours of >16 h per week were significantly more likely to
      perceive all four adverse patient outcomes than participants working an extended
      <=8 h per week. LIMITATIONS: Patient outcomes were measured by respondents' self
      reports. This may not always reflect the real occurrence of adverse events.
      CONCLUSIONS: Associations between extended work hours and outcomes for patients,
      nurses and the organization were found. The findings demonstrate that working two
      shifts (16 h) more than the regular work hours lead to negative outcomes for
      patients, nurses and the organization. IMPLICATIONS FOR NURSING AND HEALTH
      POLICY: Our findings add to increasing international evidence that nurses' poor
      working conditions result in negative outcomes for professionals, patients and
      health systems. Policymakers need to be aware of the issues regarding nurses'
      extended work hours, which has been found to contribute to burnout. Urgently,
      nurse and health administrators need to develop and implement appropriate nursing
      overtime policies and strategies to help reduce this phenomenon, including
      measures to overcome the nursing shortage.

PMID- 25997842
TI  - What would Batman do? Self-distancing improves executive function in young
      children.
AB  - This experimental research assessed the influence of graded levels of self
      distancing - psychological distancing from one's egocentric perspective - on
      executive function (EF) in young children. Three- (n = 48) and 5-year-old (n =
      48) children were randomly assigned to one of four manipulations of distance from
      the self (from proximal to distal: self-immersed, control, third person, and
      exemplar) on a comprehensive measure of EF. Performance increased as a function
      of self-distancing across age groups. Follow-up analyses indicated that 5-year
      olds were driving this effect. They showed significant improvements in EF with
      increased distance from the self, outperforming controls both when taking a third
      person perspective on the self and when taking the perspective of an exemplar
      other (e.g., Batman) through role play. Three-year-olds, however, did not show
      increased EF performance as a function of greater distance from the self.
      Preliminary results suggest that developments in theory of mind might contribute
      to these age-related differences in efficacy. These findings speak to the
      importance of psychological distancing in the expression of conscious control
      over thought and action from a young age and suggest a promising new avenue for
      early EF intervention. 

PMID- 25997843
TI  - Flourishing in a fragmented world.

PMID- 25997844
TI  - Multi-contaminant analysis of organophosphate and halogenated flame retardants in
      food matrices using ultrasonication and vacuum assisted extraction, multi-stage
      cleanup and gas chromatography-mass spectrometry.
AB  - A multi-residue analytical method was developed for the determination of a range
      of flame retardants (FRs), including polybrominated diphenyl ethers (PBDEs),
      emerging halogenated FRs (EFRs) and organophosphate FRs (PFRs), in food matrices.
      An ultrasonication and vacuum assisted extraction (UVAE), followed by a multi
      stage clean-up procedure, enabled the removal of up to 1g of lipid from 2.5 g of
      freeze-dried food samples and significantly reduce matrix effects. UVAE achieves
      a waste factor (WF) of about 10%, while the WFs of classical QuEChERS methods
      range usually between 50 and 90%. The low WF of UVAE leads to a dramatic
      improvement in the sensitivity along with saving up to 90% of spiking (internal)
      standards. Moreover, a two-stage clean-up on Florisil and aminopropyl silica was
      introduced after UVAE, for an efficient removal of pigments and residual lipids,
      which led to cleaner extracts than normally achieved by dispersive solid phase
      extraction (d-SPE). In this way, the extracts could be concentrated to low
      volumes, e.g. <100 MUL and the equivalent matrix concentrations were up to 100g
      ww/mL. The final analysis of PFRs was performed on GC-EI-MS, while PBDEs and EFRs
      were measured by GC-ECNI-MS. Validation tests were performed with three food
      matrices (lean beef, whole chicken egg and salmon filet), obtaining acceptable
      recoveries (66-135%) with good repeatability (RSD 1-24%, mean 7%). Method LOQs
      ranged between 0.008 and 0.04 ng/g dw for PBDEs, between 0.08 and 0.20 ng/g dw
      for EFRs, and between 1.4 and 3.6 ng/g dw for PFRs. The method was further
      applied to eight types of food samples (including meat, eggs, fish, and seafood)
      with lipid contents ranging from 0.1 to 22%. Various FRs were detected above MLOQ
      levels, demonstrating the wide-range applicability of our method. To the best of
      our knowledge, this is the first method reported for simultaneous analysis of
      brominated and organophosphate FRs in food matrices.

PMID- 25997845
TI  - Quantitative determination of 13 organophosphorous flame retardants and
      plasticizers in a wastewater treatment system by high performance liquid
      chromatography tandem mass spectrometry.
AB  - A method for quantitative determination of 13 organophosphorous compounds (OPs)
      was developed and applied to influent, primary sludge, activated sludge,
      biosolids, primary effluent and final effluent from a wastewater treatment plant
      (WWTP). The method involved solvent extraction followed by solid phase clean-up
      and analysis by high performance liquid chromatography positive electrospray
      ionization-tandem mass spectrometry (HPLC(+ESI)MS/MS). Replicate spike/recovery
      experiments revealed the method to have good accuracy (70-132%) and precision
      (<19% RSD) in all matrices. Detection limits of 0.1-5 ng/L for aqueous samples
      and 0.01-0.5 ng/g for solid samples were achieved. In the liquid waste stream ?OP
      concentrations were highest in influent (5764 ng/L) followed by primary effluent
      (4642 ng/L), and final effluent (2328 ng/L). In the solid waste stream, the
      highest ?OP concentrations were observed in biosolids (3167 ng/g dw), followed by
      waste activated sludge (2294 ng/g dw), and primary sludge (2128 ng/g dw). These
      concentrations are nearly 30-fold higher than ?polybrominated diphenyl ether
      (BDE) concentrations in influents and nearly 200-fold higher than ?BDE
      concentrations in effluents from other sites in Canada. Tetrekis(2
      chlorethyl)dichloroisopentyldiphosphate (V6), tripropylphosphate (TnPrP), and
      Tris(2,3-dibromopropyl)phosphate (TDBPP) are investigated for the first time in a
      WWTP. While TnPrP and TDBB were not detected, V6 was observed at concentrations
      up to 7.9 ng/g in solid waste streams and up to 40.7 ng/L in liquid waste
      streams. The lack of removal of OPs during wastewater treatment is a concern due
      to their release into the aquatic environment.

PMID- 25997846
TI  - Carboxylated solid carbon spheres as a novel solid-phase microextraction coating
      for sensitive determination of phenols in environmental water samples.
AB  - The high performance separation and enrichment of polar phenols from aqueous
      matrices is often difficult due to the strong interactions between phenols and
      water. In this paper, carboxylated solid carbon spheres (SCSs-COOH) were, for the
      first time, used as a novel coating material in the solid-phase microextraction
      (SPME) of polar phenols at ultra-trace levels in environmental water samples. Gas
      chromatography coupled with tandem mass spectrometry (GC-MS/MS) was applied for
      sample quantification and detection. The novel SCSs-COOH-coated fiber exhibited
      good thermal stability (>330  degrees C) and higher extraction efficiency than
      commercial fibers in the extraction of phenols. The Plackett-Burman design was
      employed to optimize the extraction factors affecting the extraction efficiency
      through a response surface methodology. A possible phenol extraction mechanism
      enabled by the SCSs-COOH-coated fiber is proposed. Under the optimized
      conditions, low detection limits (0.26-2.63 ng L(-1)), a wide linear range (1
      1000 ng L(-1)), good repeatability (2.00-9.02%, n=5) and excellent
      reproducibility (2.08-8.55%, n=3) were achieved. The developed method was
      validated against several environmental water samples, with satisfactory results
      being obtained each case.

PMID- 25997847
TI  - Metal-organic framework UiO-66 modified magnetite@silica core-shell magnetic
      microspheres for magnetic solid-phase extraction of domoic acid from shellfish
      samples.
AB  - Fe3O4@SiO2@UiO-66 core-shell magnetic microspheres were synthesized and
      characterized by transmission electron microscopy, scanning electron microscopy,
      X-ray diffraction, Fourier transform infrared spectrometry, vibrating sample
      magnetometry, nitrogen adsorption porosimetry and zeta potential analyzer. The
      synthesized Fe3O4@SiO2@UiO-66 microspheres were first used for magnetic solid
      phase extraction (MSPE) of domoic acid (DA) in shellfish samples. Combined with
      high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), a
      fast, simple and sensitive method for the determination of DA was established
      successfully. Under the optimized conditions, the developed method showed short
      analysis time, good linearity (r(2) = 0.9990), low limit of detection (1.45 pg
      mL(-1); S/N = 3:1), low limit of quantification (4.82 pg mL(-1); S/N = 10:1), and
      good extraction repeatability (RSD <= 5.0%; n = 5). Real shellfish samples were
      processed using the developed method, and trace level of DA was detected. The
      results demonstrate that Fe3O4@SiO2@UiO-66 core-shell magnetic microspheres are
      the promising sorbents for rapid and efficient extraction of polar analytes from
      complex biological samples.

PMID- 25997848
TI  - Assessing models for genetic prediction of complex traits: a comparison of
      visualization and quantitative methods.
AB  - BACKGROUND: In silico models have recently been created in order to predict which
      genetic variants are more likely to contribute to the risk of a complex trait
      given their functional characteristics. However, there has been no comprehensive
      review as to which type of predictive accuracy measures and data visualization
      techniques are most useful for assessing these models. METHODS: We assessed the
      performance of the models for predicting risk using various methodologies, some
      of which include: receiver operating characteristic (ROC) curves, histograms of
      classification probability, and the novel use of the quantile-quantile plot.
      These measures have variable interpretability depending on factors such as
      whether the dataset is balanced in terms of numbers of genetic variants
      classified as risk variants versus those that are not. RESULTS: We conclude that
      the area under the curve (AUC) is a suitable starting place, and for models with
      similar AUCs, violin plots are particularly useful for examining the distribution
      of the risk scores.

PMID- 25997849
TI  - Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases
      in China.
AB  - PURPOSE: This study explored the clinical characteristics, diagnosis and
      treatments of primary blepharospasm. METHODS: In this retrospective analysis, 100
      patients with blepharospasm were enrolled. Data were collected from medical
      records and face-to-face interviews with patients and their families. RESULTS:
      The age of onset was 56.4 +/- 2.7 (range, 32-76 years). The duration between
      onset and accurate diagnosis was 38.7 +/- 36.0 months (range, 2-120 months). Dry
      eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%.
      Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most
      confusion in the differential diagnosis. Regular botulinum toxin type A
      injections improved both eyelid spasms and subjective ocular symptoms in all
      patients. CONCLUSIONS: Regular botulinum toxin type A injections improved both
      eyelid spasms and subjective ocular symptoms in blepharospasm patients. The
      differentiation of primary blepharospasm differentiation from dry eye syndrome,
      conjunctivitis/keratitis and myasthenia gravis must be improved.

PMID- 25997850
TI  - Real world research: a complementary method to establish the effectiveness of
      acupuncture.
AB  - BACKGROUND: Acupuncture has been widely used in the management of a variety of
      diseases for thousands of years, and many relevant randomized controlled trials
      have been published. In recent years, many randomized controlled trials have
      provided controversial or less-than-convincing evidence that supports the
      efficacy of acupuncture. The clinical effectiveness of acupuncture in Western
      countries remains controversial. DISCUSSION: Acupuncture is a complex
      intervention involving needling components, specific non-needling components, and
      generic components. Common problems that have contributed to the equivocal
      findings in acupuncture randomized controlled trials were imperfections regarding
      acupuncture treatment and inappropriate placebo/sham controls. In addition, some
      inherent limitations were also present in the design and implementation of
      current acupuncture randomized controlled trials such as weak external validity.
      The current designs of randomized controlled trials of acupuncture need to be
      further developed. In contrast to examining efficacy and adverse reaction in a
      "sterilized" environment in a narrowly defined population, real world research
      assesses the effectiveness and safety of an intervention in a much wider
      population in real world practice. For this reason, real world research might be
      a feasible and meaningful method for acupuncture assessment. Randomized
      controlled trials are important in verifying the efficacy of acupuncture
      treatment, but the authors believe that real world research, if designed and
      conducted appropriately, can complement randomized controlled trials to establish
      the effectiveness of acupuncture. Furthermore, the integrative model that can
      incorporate randomized controlled trial and real world research which can
      complement each other and potentially provide more objective and persuasive
      evidence.

PMID- 25997851
TI  - The role of the prostaglandin E2 receptors in vulnerability of oligodendrocyte
      precursor cells to death.
AB  - BACKGROUND: Activity of cyclooxygenase 2 (COX-2) in mouse oligodendrocyte
      precursor cells (OPCs) modulates vulnerability to excitotoxic challenge. The
      mechanism by which COX-2 renders OPCs more sensitive to excitotoxicity is not
      known. In the present study, we examined the hypothesis that OPC excitotoxic
      death is augmented by COX-2-generated prostaglandin E2 (PGE2) acting on specific
      prostanoid receptors which could contribute to OPC death. METHODS: Dispersed OPC
      cultures prepared from mice brains were examined for expression of PGE2 receptors
      and the ability to generate PGE2 following activation of glutamate receptors with
      kainic acid (KA). OPC death in cultures was induced by either KA, 3'-O-(Benzoyl)
      benzoyl ATP (BzATP) (which stimulates the purinergic receptor P2X7), or TNFalpha,
      and the effects of EP3 receptor agonists and antagonists on OPC viability were
      examined. RESULTS: Stimulation of OPC cultures with KA resulted in nearly a
      twofold increase in PGE2. OPCs expressed all four PGE receptors (EP1-EP4) as
      indicated by immunofluorescence and Western blot analyses; however, EP3 was the
      most abundantly expressed. The EP3 receptor was identified as a candidate
      contributing to OPC excitotoxic death based on pharmacological evidence.
      Treatment of OPCs with an EP1/EP3 agonist 17 phenyl-trinor PGE2 reversed
      protection from a COX-2 inhibitor while inhibition of EP3 receptor protected OPCs
      from excitotoxicity. Inhibition with an EP1 antagonist had no effect on OPC
      excitotoxic death. Moreover, inhibition of EP3 was protective against toxic
      stimulation with KA, BzATP, or TNFalpha. CONCLUSION: Therefore, inhibitors of the
      EP3 receptor appear to enhance survival of OPCs following toxic challenge and may
      help facilitate remyelination.

PMID- 25997852
TI  - A woman with upper and lower airway symptoms.

PMID- 25997853
TI  - IFN Regulatory Factor-1 Modulates the Function of Dendritic Cells in Patients
      with Acute Coronary Syndrome.
AB  - BACKGROUND: Atherosclerosis is widely recognized as a complex inflammatory
      disease involving pathogenic immune response of T cells and antigen-presenting
      cells (APCs) such as dendritic cells (DCs) and macrophages. Accumulating evidence
      has revealed that mature DCs play critical roles in the differentiation of
      effector T cells into CD4+ T cells, which effectively participate in the onset of
      acute coronary syndrome (ACS). IFN regulatory factor (IRF)-1 has been shown to be
      involved in various immune processes. The role of IRF-1 in DCs in the
      pathogenesis of ACS has not been investigated. METHODS AND RESULTS: We examined
      the relative mRNA and protein expression of IRF-1 in human monocyte-derived DCs
      in patients with coronary artery disease (CAD). The overexpression or silencing
      of IRF-1 expression in DCs in patients with ACS was performed to explore the
      possible role of IRF-1 in the maturation and function of DCs involved in ACS. The
      results showed that the relative expression of IRF-1 in DCs is obviously
      increased in patients with ACS. The overexpression or silencing of IRF-1
      expression could effectively promote or attenuate the maturation and function of
      DCs. In addition, we revealed that the MAPK pathway (phosphorylation of JNK, p38
      and ERK1/2) might be downstream of IRF-1 signalling pathway in activation of
      circulating DCs in ACS patients. CONCLUSION: The present data demonstrate that
      IRF-1 could effectively promote the immune maturation and function of DCs in ACS
      patients.

PMID- 25997854
TI  - Improvement of cell membrane permeability using a cell-solution electrode for
      generating atmospheric-pressure plasma.
AB  - The cell membrane permeability, which is strongly related to gene transfection,
      is improved using a cell-solution electrode for generating atmospheric-pressure
      plasma (APP) just above the solution. In the case of the floating cells, the cell
      membrane permeability is significantly improved by the cell-solution electrode
      APP compared with the conventional diffusion type APP, because the distance
      between the plasma generation area and the cell solution surface becomes short,
      which could reduce the radial diffusion loss of the plasma irradiated to the cell
      suspended solution. In the case of the adherent cells, cell membrane permeability
      is found to be enhanced by the shorter distance between the solution surface and
      the adherent cells as well as using the cell-solution electrode, which means that
      the short-lived reactive oxygen species generated at the solution surface are
      essential for the improvement of cell membrane permeability.

PMID- 25997856
TI  - Tailored Tamoxifen Treatment for Breast Cancer Patients: A Perspective.
AB  - Tamoxifen, an endocrine agent, is widely used in the treatment of estrogen
      receptor-positive breast cancer. It has greatly reduced disease recurrence and
      mortality rates of breast cancer patients, however, not all patients benefit from
      tamoxifen treatment because in approximately 25% to 30% of the patients the
      disease recurs. Many researchers have sought to find factors associated with
      endocrine treatment outcome in the past years, however, this quest has not been
      finished. In this article, we focus on a factor that might influence outcome of
      tamoxifen treatment: interpatient variability in tamoxifen pharmacokinetics. In
      recent years it has become clear that tamoxifen undergoes extensive metabolism
      and that some of the formed metabolites are much more pharmacologically active
      than tamoxifen itself. Despite the wide interpatient variability in tamoxifen
      pharmacokinetics and pharmacodynamics, all patients receive a standard dose of 20
      mg tamoxifen per day. Different approaches can be pursued to individualize
      tamoxifen dosing: genotyping, phenotyping, and therapeutic drug monitoring.
      Therapeutic drug monitoring seems to be the most direct and promising approach,
      however, further clinical research is warranted to establish the added value of
      individual dosing in tamoxifen treatment optimization. 

PMID- 25997855
TI  - Characterization of Durable Responder for Capecitabine Monotherapy in Patients
      With Anthracycline- and Taxane-Pretreated Metastatic Breast Cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate predictive factors and the
      clinical characteristics of durable responders to capecitabine monotherapy in
      heavily-treated patients with metastatic breast cancer (MBC). PATIENTS AND
      METHODS: Between December 2000 and May 2012, a total of 236 evaluable patients
      with MBC who had been treated with second- or greater-line palliative
      capecitabine monotherapy after a previous treatment regimen with anthracycline
      and taxane were included. Capecitabine (1250 mg/m(2) twice daily) was
      administered for 2 weeks followed by a 1-week rest period. RESULTS: The response
      rate was 23.3% and median progression-free survival (PFS) was 4.7 months (95%
      confidence interval, 4.0-5.5). Among 236 patients, 33 patients (14.0%) showed
      durable response (>12 months) to capecitabine monotherapy. Patients with durable
      response showed significantly greater incidence of estrogen receptor (ER)
      positivity (81.8% vs. 59.1%; P = .012), single-organ metastasis (51.5% vs. 32.0%;
      P = .047), and absence of lymph node metastasis (75.8% vs. 54.2%; P = .023),
      compared with patients without durable response. In multivariate analysis, ER
      positivity and single-organ metastasis retained a significant association with
      better PFS to capecitabine monotherapy (hazard ratio [HR], 0.51; P < .001 and HR,
      0.62; P = .004). CONCLUSION: Our data suggest that ER positivity and single-organ
      metastasis can be useful predictive markers for better PFS to second- or greater
      line palliative capecitabine monotherapy in anthracycline- and taxane-pretreated
      MBC patients.

PMID- 25997857
TI  - Layer-specific endocannabinoid-mediated long-term depression of GABAergic
      neurotransmission onto principal neurons in mouse visual cortex.
AB  - Visually induced endocannabinoid-mediated long-term depression of GABAergic
      neurotransmission (iLTD) mediates the maturation of GABAergic release in layer
      2/3 of visual cortex. Here we examined whether the maturation of GABAergic
      transmission in other layers of visual cortex also requires endocannabinoids. The
      developmental plasticity of GABAergic neurotransmission onto the principal
      neurons in different layers of mouse visual cortex was examined in cortical
      slices by whole-cell recordings of inhibitory postsynaptic currents evoked by
      presynaptic inhibitory inputs. Theta burst stimulation of GABAergic inputs
      induced an endocannabinoid-mediated long-term depression of GABAergic
      neurotransmission onto pyramidal cells in layer 2/3 from postnatal day (P)10 to
      30 and in layer 5 from P10 to 40, whereas that of GABAergic inputs did not induce
      iLTD onto star pyramidal neurons in layer 4 at any time postnatally, indicating
      that this plasticity is laminar-specific. The developmental loss of iLTD
      paralleled the maturation of GABAergic inhibition in both layer 2/3 and layer 5.
      Visual deprivation delayed the developmental loss of iLTD in layers 3 and 5
      during a critical period, while 2 days of light exposure eliminated iLTD in both
      layers. Furthermore, the GABAergic synapses in layers 2/3 and 5 did not normally
      mature in the type 1 cannabinoid receptor knock-out mice, whereas those in layer
      4 did not require endocannabinoid receptor for maturation. These results suggest
      that visually induced endocannabinoid-dependent iLTD mediates the maturation of
      GABAergic release in extragranular layer rather than in granular layer of mouse
      visual cortex. 

PMID- 25997859
TI  - Efficacy and Safety of White Willow Bark (Salix alba) Extracts.
AB  - Willow bark extract has been used for thousands of years as an anti-inflammatory,
      antipyretic, and analgesic. In spite of its long history of use, relatively few
      human and animal studies have been published that confirm anecdotal observations.
      A small number of clinical studies have been conducted that support the use of
      willow bark extracts in chronic lower back and joint pain and osteoarthritis.
      Willow bark extracts also are widely used in sports performance and weight loss
      products presumably because of anti-inflammatory and analgesic activities,
      although no human studies have been published that specifically and directly
      document beneficial effects. In recent years, various in vitro and animal studies
      have demonstrated that the anti-inflammatory activity of willow bark extract is
      associated with down regulation of the inflammatory mediators tumor necrosis
      factor-alpha and nuclear factor-kappa B. Although willow bark extracts are
      generally standardized to salicin, other ingredients in the extracts including
      other salicylates as well as polyphenols, and flavonoids may also play prominent
      roles in the therapeutic actions. Adverse effects appear to be minimal as
      compared to non-steroidal anti-inflammatory drugs including aspirin. The primary
      cause for concern may relate to allergic reactions in salicylate-sensitive
      individuals.

PMID- 25997860
TI  - Quantum-CORMs: quantum dot sensitized CO releasing molecules.
AB  - The synthesis and photodecomposition behaviour of a family of CO releasing
      molecules (CORMs) based on [Mn(CO)3bpy] derivatives connected to a semiconductor
      Quantum Dot (QD) sensitizer is described here. Compared to the non-sensitized
      complexes, such systems show a 2 to 6-fold increase of the photodecomposition
      rate upon irradiation with visible light. 

PMID- 25997858
TI  - Synthesis of (68)Ga-labeled NOTA-RGD-GE11 heterodimeric peptide for dual integrin
      and epidermal growth factor receptor-targeted tumor imaging.
AB  - Radiolabeled Arg-Gly-Asp (RGD) peptide analogs have been extensively studied for
      alphavbeta3 integrin-targeted angiogenesis imaging. According to recently
      presented evidence, the dodecapeptide GE11 has high affinity to the epidermal
      growth factor receptor (EGFR), which is overexpressed in many types of cancer.
      Dual-receptor molecular imaging probes with two different heterodimeric peptides
      exhibit improved cancer targeting efficacy. In the present study, the design and
      synthesis of a new RGD-GE11 peptide heterodimer for dual alphavbeta3
      integrin/EGFR-targeted cancer imaging are described. The RGD-GE11 heterodimer was
      linked with 6-aminohexanoic acid (6-Ahx) and cysteine and conjugated with 1,4,7
      triazacyclononane-N,N',N"-triacetic acid (NOTA) to form NOTA-RGD-cys-6-Ahx-GE11.
      The monomeric peptides, NOTA-cys-6-Ahx-GE11 and c(RGDyK), were formed by a
      peptide synthesizer. The peptide heterodimer NOTA-RGD-GE11 was obtained by NOTA
      cys-6-Ahx-GE11 and maleimidopropyl-c(RGDyK) conjugation with a thioether linkage.
      The NOTA peptide conjugate was labeled with freshly eluted (68)Ga and purified
      using reversed-phase high-performance liquid chromatography. The (68)Ga-NOTA-RGD
      cys-6-Ahx-GE11 was successfully prepared, in this study, with a radiochemical
      yield of 85% and a radiochemical purity of >98%. These results warrant further
      investigation of this heterodimeric peptide's binding affinity to the receptors.

PMID- 25997861
TI  - High-Resolution Physical Chromosome Mapping of Multigene Families in Lagria
      villosa (Tenebrionidae): Occurrence of Interspersed Ribosomal Genes in
      Coleoptera.
AB  - The organization and mapping of multigene families can produce useful genetic
      markers, and its use may elucidate the mechanisms of karyotype variation and
      genomic organization in different groups of eukaryotes. To date, few species of
      Coleoptera have been analyzed using FISH for the location of multigene families.
      The purpose of this study was to use high-resolution chromosome mapping to
      establish the genomic organization of the 18S rDNA, 5S rDNA and histone H3 gene
      families in Lagria villosa. FISH was performed using 18S rDNA, 5S rDNA and
      histone H3 probes prepared via PCR labeling. Fiber-FISH for 18S and 5S rDNA
      indicated that both ribosomal elements are colocalized in the short arm of
      chromosome 4. Additionally, FISH, using the histone H3 probe, revealed that this
      sequence is found in only one autosomal pair and did not colocalize with rDNA.
      Fiber-FISH with 5S and 18S probes, used to improve the mapping resolution of
      these regions, showed that both genes are closely interspersed with varying
      amounts of both DNA classes. 

PMID- 25997862
TI  - Learning effects of the sensory organization test as a measure of postural
      control and balance in Parkinson's disease.
AB  - INTRODUCTION: Recent experiments examining balance in Parkinson's disease (PD)
      have used the sensory organization test (SOT) to measure postural control and
      balance. Use of the SOT raises the question as to whether people will improve
      after undergoing the test multiple times or if there is a learning effect plateau
      after multiple trials. The objective of this study was to determine whether there
      is a learning effect using the SOT in subjects with PD both fallers and non
      fallers, and healthy controls. METHODS: Nineteen subjects completed the study.
      Ten subjects with PD who were non-fallers (PD-Non-fallers), nine subjects with PD
      who were fallers (PD-Faller), and 10 healthy controls (Controls). Subjects
      completed 5 SOT testing sessions over a 3 week period. Those with PD were tested
      at the same time in their peak 'on' period. RESULTS: The PD-Faller groups SOT
      composite score improved from session 1 to session 4 and 5. In the Control group
      the composite score improved from session 1 to session 5. There was no change
      from session 1 to session 5 in the PD Non-faller group. The PD-Faller group had
      significantly lower composite scores than our PD Non-faller group and our
      Controls. Our PD-Non-faller group scores were similar to Controls. CONCLUSION:
      Multiple baseline measures are usually recommended for any task used as an
      outcome measure. Our findings suggest that in PD subjects who are considered
      fallers that by the fourth session any improvement may be due to a learning
      effect.

PMID- 25997863
TI  - A longitudinal study of non-motor symptom burden in Parkinson's disease after a
      transition to expert care.
AB  - BACKGROUND: Non-motor symptoms (NMS) are common among patients with Parkinson's
      disease (PD) however little is known about their progression in terms of severity
      or burden after referral to expert care. OBJECTIVE: This study was aimed to
      establish the progression of NMS burden in PD patients after referral to tertiary
      healthcare centre and factors affecting it. METHODS: Newly referred PD patients
      were prospectively enrolled and follow-up for up to 18 months. Non-motor symptoms
      scale (NMSS) was used to evaluate the burden of non-motor symptoms. RESULTS:
      There was a significant median reduction of total NMS burden over the follow-up
      period. Similarly all NMS domains except domains 2 (sleep/fatigue), 3
      (mood/cognition), 6 (gastrointestinal) and 7 (urinary) showed significant median
      reduction of scores. In the univariate regression analysis, Hoehn & Yahr staging,
      disease duration, visit, Schwab & England Activities of Daily Living score and
      UPDRS motor scores were individually predictive of change in total NMS burden.
      However, in the multivariable regression analysis only the latter three were
      significantly predictive of change in the total NMS burden. CONCLUSION: There was
      a significant reduction of total NMS burden over the study period. The severity
      of motor and activity of daily living impairments as well as subsequent visit
      were the best predictors of NMS change.

PMID- 25997864
TI  - Remote control of apomorphine infusion rate in Parkinson's disease: Real-time
      dose variations according to the patients' motor state. A proof of concept.

PMID- 25997865
TI  - Application of toxicity identification evaluation procedure to toxic industrial
      effluent in South Korea.
AB  - Toxicity identification evaluation (TIE) was applied to the effluent from a
      pharmaceutical industrial complex, following the US EPA TIE guidelines. The whole
      effluent toxicity (WET) test found toxicity greater than 16toxic units (TU) in
      the effluent. Dissolved non-polar organic compounds were identified as the major
      contributor to the observed toxicity in the TIE manipulations in phases I and II.
      Among the 48 organic compounds identified, three compounds (i.e., acetophenone,
      benzoimide, and benzothiazole) were related to the pharmaceutical production
      procedure; however, no contribution to toxicity was predicted in the compounds.
      The results of the ECOSAR model, which predicts toxicity, indicated that the
      alkane compounds caused significant toxicity in the effluent. The toxicity test
      and heavy metal analysis, which used IC and ICP/MS, identified that particulate
      and heavy metals, such as Cu and Zn, contributed to the remaining toxicity,
      except dissolved organics. The results showed the applicability of the TIE method
      for predicting regional effluents produced by the industrial pharmaceutical
      complex in this study. Although the location was assumed to be affected by
      discharge of pharmaceutical related compounds in the river, no correlations were
      observed in the study. Based on the results, advanced treatment processes, such
      as activated carbon adsorption, are recommended for the wastewater treatment
      process in this location. 

PMID- 25997866
TI  - A high-fish-oil diet prevents adiposity and modulates white adipose tissue
      inflammation pathways in mice.
AB  - Fish oil improves obesity and its comorbidities, but its mechanisms of action
      remain unknown. We evaluate the effects of a diet rich in fish oil in white
      adipose tissue (WAT) inflammation pathways, renin-angiotensin system (RAS) and
      mitogen-activated protein kinases (MAPKs). To achieve our aims, four groups of
      male C57BL/6 mice were fed different diets: standard chow diet (SC; 10% energy
      from fat), SC+fish oil diet (SC-FO; 10% energy from fat), high-fat lard diet (HF
      L; 50% energy from lard) and HF fish oil diet (HF-FO; 50% energy from fish oil).
      We evaluated body mass, epididymal fat pad mass, food intake and glucose
      tolerance. In WAT, we assessed adipocyte hypertrophy, monocyte chemotactic
      protein-1 immunofluorescence, and gene and protein expression of insulin
      signaling, inflammation, MAPKs, RAS, peroxisome proliferator-activated receptors
      (PPARs) and AMP-activated protein kinase (AMPK). In relation to the results, the
      HF-L group, as expected, showed elevated body mass and adiposity, glucose
      intolerance and hypertrophied adipocytes. In WAT, we found a defect in insulin
      signaling, infiltration of macrophages and inflammatory markers with the
      associated activation of MAPKs and local RAS. On the contrary, the HF-FO group
      did not present increased body mass, adiposity or glucose intolerance. In this
      group, insulin signaling, macrophage infiltration and inflammation were reduced
      in WAT in comparison with the HF-L group. We also observed decreases of MAPKs and
      local RAS and elevation of PPAR and AMPK. In summary, fish oil activates PPAR
      (the three isoforms) and AMPK, decreases WAT insulin resistance and inflammation,
      and inhibits MAPK and RAS pathways activation.

PMID- 25997868
TI  - Binaural integration of periodically alternating speech following cochlear
      implantation in subjects with profound sensorineural unilateral hearing loss.
AB  - In cochlear implant (CI) recipients with unilateral hearing loss (UHL) and normal
      hearing (NH) in the contralateral ear, the central auditory system receives
      signals of different auditory modalities, i.e. electrically via the CI ear as
      well as acoustically via the NH ear. The present study investigates binaural
      integration of bimodal stimulation in the central auditory system of 10 CI
      subjects with UHL by applying a modified version of the Rapidly Alternating
      Speech Perception (RASP) test to characterise speech recognition ability under
      monotic and dichotic listening arrangements. Subsequently, the results for each
      monotic and dichotic test condition were compared to quantify the binaural
      benefit from CI usage. The study results demonstrate significantly improved
      speech recognition under dichotic compared to monotic listening conditions,
      providing evidence that there is binaural integration of acoustically and
      electrically transmitted speech segments in the central nervous system at
      brainstem and cortical levels. In contrast to more commonly used tests of
      binaural integration, such as localisation, the RASP test provides the clinical
      option to investigate binaural integration involving structures at the cortical
      level.

PMID- 25997867
TI  - EGR-1/Bax pathway plays a role in vitamin E delta-tocotrienol-induced apoptosis
      in pancreatic cancer cells.
AB  - The anticancer activity of delta-tocotrienol, a bioactive vitamin E present in
      whole grain cereals, annatto beans and palm fruit, is strongly dependent on its
      effect on the induction of apoptosis. delta-Tocotrienol-induced apoptosis is
      associated with consistent induction in the expression of the proapoptotic
      protein Bcl-2-associated X protein (Bax). The molecular mechanism by which delta
      tocotrienol regulates Bax expression is unknown. We carried out a DNA microarray
      study that identified delta-tocotrienol induction of the zinc finger
      transcription factor EGR-1 in pancreatic cancer cells. Here, we provide evidence
      linking delta-tocotrienol-induced apoptosis in pancreatic cancer cells to EGR-1
      regulation of Bax expression. Forced expression of EGR-1 induces Bax expression
      and apoptosis in pancreatic cancer cells. In contrast, knockdown of delta
      tocotrienol-induced EGR-1 by small interfering RNA attenuated delta-tocotrienol
      induced Bax expression and reduced delta-tocotrienol-induced apoptosis. Further
      analyses showed that de novo protein synthesis was not required for delta
      tocotrienol-induced EGR-1 expression, suggesting a direct effect of delta
      tocotrienol on EGR-1 expression. Furthermore, a chromatin immunoprecipitation
      assay demonstrated that EGR-1 binds to the Bax gene promoter. Finally, delta
      tocotrienol treatment induced Bax expression and activated EGR-1 in the
      pancreatic neoplastic cells of the PDX-Cre Kras genetically engineered model of
      pancreatic cancer. Our study provides the first evidence for EGR-1 as a direct
      target of vitamin E delta-tocotrienol, suggesting that EGR-1 may act as a
      proapoptotic factor in pancreatic cancer cells via induction of Bax. 

PMID- 25997869
TI  - The impact of JAK2V617F mutation on different types of thrombosis risk in
      patients with essential thrombocythemia: a meta-analysis.
AB  - To assess the effect of JAK2V617F on different thrombotic risks in essential
      thrombocythemia (ET) patients, we identified eligible studies from several
      databases including Pubmed, Embase, and Cochrane Central Register of Controlled
      Trials (up to November 2014). Twenty-two studies of 2922 ET patients were
      included in exploring the relationship between JAK2V617F and the risk of
      thrombosis. Compared to JAK2V617F-negative ET patients, JAK2V617F-positive ET
      patients had higher odd risks (ORs) of arterial thrombosis [OR = 2.59 (1.84
      3.65)] and venous thrombosis [OR = 2.10 (1.53-2.88)]. The JAK2V617F-positive
      group was also more prone to increased risk of microcirculatory disturbances [OR
      = 1.50 (0.97-2.32)]. Moreover, JAK2V617F may indicate increased risk of either
      arterial [OR = 1.71 (1.22-2.39)] or venous thrombosis [OR = 2.90 (1.54-5.46)]
      before diagnosis of ET. During follow-up, JAK2V617F might not be related to
      arterial thrombosis [OR = 1.90 (0.90-2.08)], but rather venous thrombosis [OR =
      1.95 (1.08-3.53)]. In conclusion, JAK2V617F increased the risk of arterial and
      venous thrombosis in ET patients, while understanding its role in
      microcirculatory disturbances will require further studies. 

PMID- 25997870
TI  - High-dose methotrexate, etoposide, dexamethasone and pegaspargase (MEDA)
      combination chemotherapy is effective for advanced and relapsed/refractory
      extranodal natural killer/T cell lymphoma: a retrospective study.
AB  - Extranodal natural killer/T cell lymphoma, nasal type (ENK/TCL), is an aggressive
      and rare hematological malignancy. Patients with advanced and relapsed/refractory
      disease have very poor outcomes. In this study, we retrospectively assessed the
      efficacy and safety of MEDA regimen (methotrexate, etoposide, dexamethasone and
      pegaspargase) in the treatment of advanced and relapsed/refractory ENK/TCL
      patients. Thirteen patients received a total of 55 cycles of MEDA, with a median
      of four cycles. At the completion of treatment, the overall response rate was
      76.9 %, with a complete response rate of 61.5 %. The 1-year overall survival rate
      was 69.2 %, and 1-year progression-free survival was 61.5 %. Treatment-related
      toxicity was monitored in all patients. Grade 3/4 neutropenia occurred in 46.2 %
      of patients. Serious infections happened in two cases (15.4 %). Grade 3/4
      thrombocytopenia occurred in 30.8 % of patients, and 23.1 % received platelet
      transfusion. Grade 3/4 anemia was observed in 23.1 % of patients. Hepatotoxicity
      and low fibrinogen were common, but mild. These results show that MEDA regimen is
      very effective with tolerable adverse effects in the treatment of advanced and
      relapsed/refractory ENK/TCL. Further prospective trials are expected to validate
      the efficacy of MEDA in an expanded number of patients. 

PMID- 25997871
TI  - Evaluating the optimal serum ferritin level to identify hemophagocytic
      lymphohistiocytosis in the critical care setting.
AB  - Ferritin is known to be involved in numerous physiological roles, such as iron
      storage, as well as various pathological conditions and in generalized
      inflammatory states. Hyperferritinemia is also encountered in the setting of
      hemophagocytic lymphohistiocytosis (HLH). Current diagnostic criteria exist to
      define HLH based on several clinical and biochemical markers, including the serum
      ferritin level. In this study, we retrospectively evaluated the value of ferritin
      >500 ng/mL in diagnosing HLH in 344 consecutive patients admitted to the medical
      intensive care unit at our hospital. Nine cases of HLH were identified.
      Comparison of the HLH with the non-HLH group showed that their maximum median
      serum ferritin level was 25,652 (range 1977-100,727 ng/mL) versus 1180 (503
      85,168 ng/mL) (P < 0.001), platelets were 30 (5-92 * 10(3)/MUL) versus 113 (0-507
      * 10(3)/MUL) (P < 0.001), absolute neutrophil counts were 2.56 (0.02-23.7 *
      10(3)/MUL) versus 7.7 (0.01-82.7 * 10(3)/MUL) (P = 0.002), and triglycerides were
      255 (156-394 mg/dL) versus 127 (17-624 mg/dL) (P = 0.002), respectively. Using a
      receiver operating characteristic curve, the optimal maximum serum ferritin level
      for the diagnosis of HLH was 3951 ng/mL, exceeding the current diagnostic cutoff
      set forth in the HLH-2004 guidelines. These data suggest that a higher cutoff
      value of ferritin level may have improved utility in the diagnosis of secondary
      HLH in the critical care setting. 

PMID- 25997872
TI  - The Fat/Hippo signaling pathway links within-disc morphogen patterning to whole
      animal signals during phenotypically plastic growth in insects.
AB  - BACKGROUND: Insects exhibit a diversity of environmentally sensitive phenotypes
      that allow them to be an extraordinarily successful group. For example, mandible
      size in male stag beetles is exquisitely sensitive to the larval nutritional
      environment and is a reliable signal of male condition. RESULTS: To date, studies
      of how such phenotypically plastic traits develop have focused on two types of
      mechanistic processes. Local, tissue-specific genetic mechanisms specify the
      shape and approximate final size of structures, whereas whole-animal hormonal
      signaling mechanisms modulate trait growth in response to environmental
      circumstance, including the body size and nutritional state of each individual.
      Hormones such as juvenile hormone, ecdysteroids, and/or ligands of the insulin
      signaling pathway specify whether traits grow and regulate how much growth occurs
      across a diversity of insect groups. What remains to be shown is how the local,
      tissue-specific developmental genetic pathways interact with these whole animal
      hormonal signaling pathways during development to yield phenotypically plastic
      patterns of trait growth. CONCLUSIONS: Because the Fat/Hippo signaling pathway
      coordinates trait growth and development through its interactions with morphogens
      and hormonal pathways, we propose that Fat/Hippo signaling is a missing
      mechanistic link coordinating environmentally sensitive trait development in
      insects. Developmental Dynamics 244:1039-1045, 2015. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 25997873
TI  - Mortality and longevity after a spinal cord injury: systematic review and meta
      analysis.
AB  - BACKGROUND/AIMS: Mortality and longevity studies of spinal cord injury (SCI) are
      essential for informing healthcare systems and policies. This review evaluates
      the current evidence among people with SCIs worldwide in relation to the WHO
      region and country income level; demographic and lesion characteristics; and in
      comparison with the general population. METHODS: A systematic review of relevant
      databases for original studies. Pooled estimates were derived using random
      effects meta-analysis, restricted to traumatic SCI. RESULTS: Seventy-four studies
      were included. In-hospital mortality varied, with pooled estimates of 24.1% (95%
      confidence interval (CI) 14.1-38.0), 7.6% (95% CI 6.3-9.0), 7.0% (95% CI 1.5
      27.4), and 2.1% (95% CI 0.9-5.0) in the WHO regions of Africa, the Americas,
      Europe and Western Pacific. The combined estimate for low- and middle-income
      countries was nearly three times higher than for high-income countries. Pooled
      estimates of first-year survival were 86.5% (95% CI 75.3-93.1), 95.6% (95% CI
      81.0-99.1), and 94.0% (95% CI 93.3-94.6) in the Americas, Europe and Western
      Pacific. Pooled estimates of standardized mortality ratios in tetraplegics were
      2.53 (2.00-3.21) and 2.07 (1.47-2.92) in paraplegics. CONCLUSION: This study
      found substantial variation in mortality and longevity within the SCI population,
      compared to the general population, and between WHO regions and country income
      level. Improved standardization and quality of reporting is needed to improve
      inferences regarding the extent to which mortality outcomes following an SCI are
      related to healthcare systems, services and policies.

PMID- 25997875
TI  - Extracellular matrix networks in bone remodeling.
AB  - Bones are constantly remodeled throughout life to maintain robust structure and
      function. Dysfunctional remodeling can result in pathological conditions such as
      osteoporosis (bone loss) or osteosclerosis (bone gain). Bone contains 100 s of
      extracellular matrix (ECM) proteins and the ECM of the various bone tissue
      compartments plays essential roles directing the remodeling of bone through the
      coupled activity of osteoclasts (which resorb bone) and osteoblasts (which
      produce new bone). One important role for the ECM is to serve as a scaffold upon
      which mineral is deposited. This scaffold is primarily type I collagen, but other
      ECM components are involved in binding of mineral components. In addition to
      providing a mineral scaffolding role, the ECM components provide structural
      flexibility for a tissue that would otherwise be overly rigid. Although primarily
      secreted by osteoblast-lineage cells, the ECM regulates cells of both the
      osteoblast-lineage (such as progenitors, mature osteoblasts, and osteocytes) and
      osteoclast-lineage (including precursors and mature osteoclasts), and it also
      influences the cross-talk that occurs between these two oppositional cells. ECM
      influences the differentiation process of mesenchymal stem cells to become
      osteoblasts by both direct cell-ECM interactions as well as by modulating growth
      factor activity. Similarly, the ECM can influence the development of osteoclasts
      from undifferentiated macrophage precursor cells, and influence osteoclast
      function through direct osteoclast cell binding to matrix components. This
      comprehensive review will focus on how networks of ECM proteins function to
      regulate osteoclast- and osteoblast-mediated bone remodeling. The clinical
      significance of these networks on normal bone and as they relate to pathologies
      of bone mass and geometry will be considered. A better understanding of the
      dynamic role of ECM networks in regulating tissue function and cell behavior is
      essential for the development of new treatment approaches for bone loss.

PMID- 25997876
TI  - Pathogen transfer and high variability in pathogen removal by detergent wipes.
AB  - BACKGROUND: The rise in health care-associated infections has placed a greater
      emphasis on cleaning and disinfection practices. The majority of policies
      advocate using detergent-based products for routine cleaning, with detergent
      wipes increasingly being used; however, there is no information about their
      ability to remove and subsequently transfer pathogens in practice. METHODS: Seven
      detergent wipes were tested for their ability to remove and transfer
      Staphylococcus aureus, Acinetobacter baumannii, and Clostridium difficile spores
      using the 3-stage wipe protocol. RESULTS: The ability of the detergent wipes to
      remove S aureus, A baumannii, and C difficile spores from a stainless steel
      surface ranged from 1.50 log10 (range, 0.24-3.25), 3.51 log10 (range, 3.01-3.81),
      and 0.96 log10 (range, 0.26-1.44), respectively, following a 10-second wiping
      time. All wipes repeatedly transferred significant amounts of bacteria/spores
      over 3 consecutive surfaces, although the percentage of total microorganisms
      transferred from the wipes after wiping was low for a number of products.
      CONCLUSIONS: Detergent-based wipe products have 2 major drawbacks: their
      variability in removing microbial bioburden from inanimate surfaces and a
      propensity to transfer pathogens between surfaces. The use of additional
      complementary measures such as combined detergent/disinfectant-based products
      and/or antimicrobial surfaces need to be considered for appropriate infection
      control and prevention.

PMID- 25997877
TI  - Tracking sources of Staphylococcus aureus hand contamination in food handlers by
      spa typing.
AB  - We aimed to identify the source of Staphylococcus aureus contaminating hands of
      food handlers. Nasal samples and direct fingertip imprints were collected on 2
      occasions from food handlers and characterized to determine likely sources of
      hand contamination. Most hand contamination was attributable to nasal isolates of
      persistently colonized coworkers who had presumably contaminated the environment.
      Regular handwashing should be supplemented by effective environmental
      disinfection. 

PMID- 25997878
TI  - Microorganisms and complaints in outpatients with a percutaneous endoscopic
      gastrostomy catheter.
AB  - BACKGROUND: We analyzed the presence of microorganisms at the insertion site of
      percutaneous endoscopic gastrostomy (PEG) catheters of 100 patients to
      investigate the microbiologic flora and its possible relation with complaints.
      MATERIALS AND METHODS: Outpatients visiting our hospital PEG-catheter team were
      included. Symptoms and the local aspect of the skin at the insertion site were
      described systematically and swabs were taken to analyze the presence of
      pathogenic microorganisms. RESULTS: The mean age of these 100 patients (55 men)
      was 62 +/- 14 years (range, 3-89 years). Oropharyngeal carcinoma (n = 59) and
      neurologic disorders (n = 27) were the most frequent indications for a PEG
      catheter. The mean insertion time was 17 +/- 20 months (range, 3-99 months). In
      15 patients no microorganisms were found. In 85 patients we found Candida
      albicans (n = 37; 44%), Staphylococcus aureus (n = 28; 33%), Escherichia coli,
      Klebsiella, Enterobacter, and enterococci (5%-20%). None of the patients reported
      discomfort. Pain or itching was reported by 24 patients. We did not find any
      statistically significant relationship between colonization, microorganisms,
      complaints, and aspect of skin. CONCLUSIONS: The insertion sites of PEG catheters
      in outpatients are frequently colonized, especially with C albicans, S aureus,
      and E coli, without clinical consequences. We did not find a relationship between
      microorganisms at the insertion sites of PEG catheters and signs and symptoms.

PMID- 25997879
TI  - Effect of a multimodal training program and traditional lecture method on nurses'
      hand hygiene knowledge, belief, and practice: A brief report.
AB  - This study compared the effect of a multimodal training program and lecturing
      method on nurses' hand hygiene knowledge, belief, and practice. Two weeks and 3
      months after the study, nurses' in both groups received significantly higher
      scores compared with the control group. Compared with the lecturing method, the
      multimodal training program is more effective in improving nurses' hand hygiene
      knowledge, belief, and practice 3 months after the study. 

PMID- 25997880
TI  - A pilot study of Brief IPT-A delivered in primary care.
AB  - OBJECTIVE: The objective was to examine the feasibility, acceptability and
      preliminary effectiveness of a brief version of Interpersonal Psychotherapy for
      Depressed Adolescents (BIPT-A) in low-income Latino adolescents treated in an
      urban pediatric primary care setting. METHOD: Ten adolescents, ages 12 to 19
      years, who were referred by their pediatric providers and met criteria for a
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depression
      diagnosis participated. Participants received 6 weekly sessions of BIPT-A.
      Acceptability and feasibility were measured by examining session attendance,
      treatment completion and treatment satisfaction. Paired-samples t tests were used
      to preliminarily examine treatment outcome as measured by both self-report and
      clinician-administered assessments of depression, social functioning and global
      impairment. RESULTS: Ninety percent of adolescents completed treatment, with 60%
      of parents having participated in at least one session. Adolescents attended 82%
      of their treatment sessions, and all participants were very satisfied with the
      treatment they received. Significant improvement was found for all outcome
      measures. CONCLUSION: The open trial provides preliminary evidence suggesting
      that BIPT-A may be a feasible and acceptable treatment model capable of engaging
      adolescents with mild to moderate depression and impairment in treatment in a
      primary care setting.

PMID- 25997881
TI  - Use of bacterial surrogates as a tool to explore antimalarial drug interaction:
      Synergism between inhibitors of malarial dihydrofolate reductase and
      dihydropteroate synthase.
AB  - Interaction between antimalarial drugs is important in determining the outcome of
      chemotherapy using drug combinations. Inhibitors of dihydrofolate reductase
      (DHFR) such as pyrimethamine and of dihydropteroate synthase (DHPS) such as sulfa
      drugs are known to have synergistic interactions. However, studies of the
      synergism are complicated by the fact that the malaria parasite can also salvage
      exogenous folates, and the salvage may also be affected by the drugs. It is
      desirable to have a convenient system to study interaction of DHFR and DHPS
      inhibitors without such complications. Here, we describe the use of Escherichia
      coli transformed with malarial DHFR and DHPS, while its own corresponding genes
      have been inactivated by optimal concentration of trimethoprim and genetic
      knockout, respectively, to study the interaction of the inhibitors. Marked
      synergistic effects are observed for all combinations of pyrimethamine and sulfa
      inhibitors in the presence of trimethoprim. At 0.05MUM trimethoprim, sum of
      fractional inhibitory concentrations, SigmaFIC of pyrimethamine with sulfadoxine,
      pyrimethamine with sulfathiazole, pyrimethamine with sulfamethoxazole, and
      pyrimethamine with dapsone are in the range of 0.24-0.41. These results show
      synergism between inhibitors of the two enzymes even in the absence of folate
      transport and uptake. This bacterial surrogate system should be useful as a tool
      for assessing the interactions of drug combinations between the DHFR and DHPS
      inhibitors. 

PMID- 25997882
TI  - SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced
      granuloma development.
AB  - SjE16.7 is an egg-specific protein from Schistosoma japonicum that recruits
      neutrophils and initiates an inflammatory granuloma response in host tissue.
      However, since macrophages are known to be important regulators of egg granuloma
      formation we investigated the effect of SjE16.7 on this cell type. Here we report
      that SjE16.7 is a potent macrophage activator, inducing macrophage chemotaxis and
      stimulating cytokine production. Treatment of murine primary macrophages with
      SjE16.7 resulted in upregulation of both pro- and anti-inflammatory cytokines (IL
      10, IL-12, IL-6 and TNF-alpha), as well as phosphorylation of mitogen-activated
      protein kinases (MAPKs). Moreover, SjE16.7 treatment increased MHC Class II
      expression on the surface of macrophages. Importantly, in vivo blockade of
      SjE16.7 significantly reduced egg-induced pathology, as a result of decreased
      leucocyte infiltration and reduced granuloma size. Our results suggest that
      SjE16.7 is an important pathogenic factor and a potential treatment target for
      this disease. 

PMID- 25997884
TI  - Natural Leishmania infection of Phlebotomus sergenti (Diptera: Phlebotominae) in
      an endemic focus of cutaneous leishmaniasis in Sanliurfa, Turkey.
AB  - Sand flies (Diptera: Phlebotominae) were surveyed for Leishmania in various
      villages of Sanliurfa in southeast Turkey. A total of 474 sand flies were
      collected by CDC light traps. Phlebotomus sergenti Parrot (49.6%) and Phlebotomus
      papatasi (Scopoli) (48.1%) were the most abundant species, followed by
      Phlebotomus alexandri Sinton (1.05%), Phlebotomus perfiliewi Parrot (0.4%),
      Phlebotomus (Adlerius) sp. (0.2%) and Sergentomyia theodori Parrot (0.4%). 196
      female sand flies were grouped in 34 pools of max 10 specimens each and 4 pools
      of P. sergenti were found positive for Leishmania DNA, detected by using ITS-1
      primer set. This is the first molecular detection and identification of
      Leishmania tropica within naturally infected P. sergenti from the most important
      focus of anthroponotic cutaneous leishmaniasis in Turkey. The high frequency of
      P. sergenti together with natural infection by the parasite makes this species
      the probable vector of L. tropica in Sanliurfa. The data obtained from this study
      could be used in strategic planning for the control of leishmaniasis in the
      region. 

PMID- 25997883
TI  - Usage of Leptospira spp. local strains as antigens increases the sensitivity of
      the serodiagnosis of bovine leptospirosis.
AB  - Leptospirosis is a zoonotic disease that occurs worldwide, particularly in
      tropical countries. In livestock the agent is responsible for reproductive
      problems such as infertility and abortion. Serogroup Sejroe, particularly serovar
      Hardjo, prevails in cattle in several regions. The microscopic agglutination test
      (MAT) is the current method for diagnosing leptospirosis. It has been proposed
      that the inclusion of local strains could detect a larger set of seroreactive
      animals. In that context, the aim of the present study was to evaluate if the
      usage of local strains as antigens increases the sensitivity of the serodiagnosis
      of bovine leptospirosis. Blood and urine samples were collected from 314 bovines
      from several herds randomly selected in a slaughterhouse in Rio de Janeiro,
      Brazil. Serological diagnosis was made with MAT using a 21 reference-strains
      panel (MAT21). Additionally, 12 local strains (MAT33) were included as antigens.
      PCR was performed with the urine samples and it was positive on 71 out of 222
      samples (31.9%). MAT21 identified as seroreactive 173 (55.1%) out of the 314
      animals studied, with Sejroe the most common (38.1%). In MAT33, 204 (65.0%)
      animals were seroreactive with a significant increase on seroreactivity (9.9%).
      In conclusion, MAT presented with a significant increase of sensitivity when
      local strains were used as antigens. Among the local strains, 2013_U152
      (KP263062) (serogroup Shermani) and 2013_U280 (KP263069) (serogroup
      Grippotyphosa) showed to be more antigenic. 

PMID- 25997885
TI  - Simulium (Gomphostilbia) (Diptera: Simuliidae) from Southern Western Ghats,
      India: two new species and DNA barcoding.
AB  - Two new species of Simulium (Gomphostilbia) (Diptera: Simuliidae) are described
      on the basis of reared adult, pupal and larval specimens collected from Southern
      Western Ghats India. The morphological data of two new species S. (Gomphostilbia)
      panagudiense sp. n. and S. (Gomphostilbia) kottoorense sp. n. are assigned to the
      batoense species group in the subgenus Gomphostilbia. S. (Gomphostilbia)
      panagudiense sp.n. is characterized in the female by having the scutum without
      longitudinal vitta and arms of the genital fork wide basally and in the pupa by
      the stalk of ventral pair medium-long. S. (Gomphostilbia) kottoorense sp.n. is
      characterized by the arm of genital fork tapered near apex in the female and
      style in medial view 0.63 times as long as coxite in the male. Phylogeny of
      members in the genus Simulium was reconstructed based on DNA barcoding gene
      (cytochrome oxidase c subunit I). Tree analysis using new technology and maximum
      likelihood analyses are congruent with evidence of two new species in the
      subgenus Gomphostilbia and separated from other species. 

PMID- 25997886
TI  - Observation of microporous cesium salts of 12-tungstosilicic acid using scanning
      transmission electron microscopy.
AB  - Heteropolyanions and their arrays in microporous cesium salts of 12
      tungstosilicic acid, Cs2.5H1.5[SiW12O40] and Cs4.0[SiW12O40], were observed by
      aberration-corrected scanning transmission electron microscopy. Microstructures
      that form micropores in the polyoxometalates were visualized. 

PMID- 25997887
TI  - It is in his eyes.

PMID- 25997888
TI  - Gliomatosis cerebri in L-2-hydroxyglutaric aciduria.

PMID- 25997890
TI  - Simultaneous self-exfoliation and autonomous motion of MoS2 particles in water.
AB  - Two-dimensional (2D) transitional metal dichalcogenides (TMDCs) have been
      receiving significant research interest due to their unique physical and
      electronic properties. We report the design of a MoS2 based motor that can
      display simultaneous self-exfoliation and autonomous motion at the surface of
      water. Exfoliation of bulk MoS2via sodium intercalation offers an attractive way
      to obtain solution-phase 2D MoS2 nanosheets on a large scale. The motion of the
      MoS2 particles results from the surface tension gradients generated by the
      naphthalene distributed in the MoS2 particles. A combination of self-exfoliation
      and propulsion in an unmodified water environment hence leads to a new platform
      which holds great promise for new applications of TMDC materials in small scale
      motors. 

PMID- 25997889
TI  - Similar frequency of paternal uniparental disomy involving chromosome 20q
      (patUPD20q) in Japanese and Caucasian patients affected by sporadic
      pseudohypoparathyroidism type Ib (sporPHP1B).
AB  - Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance
      to parathyroid hormone that occurs in most cases in the absence of Albright's
      Hereditary Osteodystrophy (AHO). Familial forms of PHP1B are caused by maternally
      inherited microdeletions within STX16, the gene encoding syntaxin 16, or within
      GNAS, a complex genetic locus on chromosome 20q13.3 encoding Gsalpha and several
      splice variants thereof. These deletions lead either to a loss-of-methylation
      affecting GNAS exon A/B alone or to epigenetic changes involving multiple
      differentially methylated regions (DMRs) within GNAS. Broad GNAS methylation
      abnormalities are also observed in most sporadic PHP1B (sporPHP1B) cases.
      However, with the exception of paternal uniparental disomy involving chromosome
      20q (patUPD20q), the molecular mechanism leading to this disease variant remains
      unknown. We now investigated 23 Japanese sporPHP1B cases, who presented with
      hypocalcemia, hyperphosphatemia, elevated PTH levels, and occasionally with TSH
      elevations and mild AHO features. Age at diagnosis was 10.6 +/- 1.45 years.
      Calcium, phosphate, and PTH were 6.3 +/- 0.23 mg/dL, 7.7 +/- 0.33 mg/dL, and 305
      +/- 34.5 pg/mL, respectively, i.e. laboratory findings that are indistinguishable
      from those previously observed for Caucasian sporPHP1B cases. All investigated
      patients showed broad GNAS methylation changes. Eleven individuals were
      homozygous for SNPs within exon NESP and a pentanucleotide repeat in exon A/B.
      Two of these patients furthermore revealed homozygosity for numerous
      microsatellite markers on chromosome 20q raising the possibility of patUPD20q,
      which was confirmed through the analysis of parental DNA. Based on this and our
      previous reports, paternal duplication of the chromosomal region comprising the
      GNAS locus appears to be a fairly common cause of sporPHP1B that is likely to
      occur with equal frequency in Caucasians and Asians.

PMID- 25997891
TI  - Folic acid-conjugated TiO2-doped mesoporous carbonaceous nanocomposites loaded
      with Mitoxantrone HCl for chemo-photodynamic therapy.
AB  - Recently, porous carbons have showed great potential in many areas. In this
      study, TiO2-doped mesoporous carbonaceous (TiO2@C) nanoparticles were obtained by
      a simple one-pot hydrothermal treatment, folic acid (FA) was conjugated to TiO2@C
      through an amide bond, then Mitoxantrone HCl (MTX) was adsorbed onto TiO2@C-FA
      and a drug delivery system, TiO2@C-FA/MTX was obtained. TiO2@C-FA/MTX showed a
      much faster MTX release at pH 4.5 than at pH 6.0 and pH 7.4. Furthermore,
      compared with free MTX, this drug delivery system showed a dose-dependent
      cytotoxicity by varying the irradiance, and afforded higher antitumor efficacy in
      cultured PC3 cells in vitro. The ability of TiO2@C-FA/MTX to combine chemotherapy
      with photodynamic activity enhanced the cancer cell killing effect in vitro,
      demonstrating that TiO2@C-FA/MTX has a great potential for cancer therapy in the
      future. 

PMID- 25997892
TI  - Isolation and Characterization of CD271+ Stem Cells Derived from Sheep Dermal
      Skin.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have great promise in the field of
      regenerative medicine due to their differentiation potential into several
      lineages. Besides the bone marrow, MSCs can be obtained from the dermis, which
      represents a large stem cell reservoir in the skin. Sheep provide an appropriate
      large animal model for preclinical studies. In this study, we focused on the
      isolation and characterization of MSCs from sheep dermis as an alternative to
      bone marrow MSCs (bmMSCs). METHODS: Primary ovine cells were obtained from the
      dermis for comparison with bone marrow. CD271(+)/45(-) dermal MSCs (CD271-dMSCs),
      which were sorted by flow cytometry, and plastic-adherent bmMSCs were examined
      for morphology, proliferation and senescence-associated beta-galactosidase
      activity in both low and high oxygen conditions. CD271 expression on cultured
      cells was assessed by flow cytometry. Adipogenic and osteogenic potentials of
      CD271-dMSCs were evaluated by oil red O and von Kossa staining. Chondrogenic
      capacity of CD271-dMSCs and CD271(+)/CD45(-) bone marrow cells (CD271-bmMSCs) was
      detected using immunohistochemistry and measurement of sulfated
      glycosaminoglycans. RESULTS: The cell proliferation assay demonstrated no
      significant difference between CD271-dMSCs and bmMSCs under low oxygen
      conditions. Cultured CD271-dMSCs revealed much more CD271 expression compared to
      CD271-bmMSCs. CD271-dMSCs and CD271-bmMSCs showed basically similar expression of
      the cartilage-specific proteins aggrecan and collagen type II, although with a
      stronger staining in CD271-bmMSC-derived cultures. Remarkably, there was co
      expression of CD271 and aggrecan during chondrogenic differentiation, suggesting
      an involvement of CD271 in chondrogenesis. CONCLUSION: Based on these findings,
      CD271-dMSCs might serve as an appropriate alternative cell source in preclinical
      research.

PMID- 25997893
TI  - A modern literature review of carbon monoxide poisoning theories, therapies, and
      potential targets for therapy advancement.
AB  - The first descriptions of carbon monoxide (CO) and its toxic nature appeared in
      the literature over 100 years ago in separate publications by Drs. Douglas and
      Haldane. Both men ascribed the deleterious effects of this newly discovered gas
      to its strong interaction with hemoglobin. Since then the adverse sequelae of CO
      poisoning has been almost universally attributed to hypoxic injury secondary to
      CO occupation of oxygen binding sites on hemoglobin. Despite a mounting body of
      literature suggesting other mechanisms of injury, this pathophysiology and its
      associated oxygen centric therapies persists. This review attempts to elucidate
      the remarkably complex nature of CO as a gasotransmitter. While CO's affinity for
      hemoglobin remains undisputed, new research suggests that its role in nitric
      oxide release, reactive oxygen species formation, and its direct action on ion
      channels is much more significant. In the course of understanding the
      multifaceted character of this simple molecule it becomes apparent that current
      oxygen based therapies meant to displace CO from hemoglobin may be insufficient
      and possibly harmful. Approaching CO as a complex gasotransmitter will help guide
      understanding of the complex and poorly understood sequelae and illuminate
      potentials for new treatment modalities. 

PMID- 25997894
TI  - Stimulating basal mitochondrial respiration decreases doxorubicin apoptotic
      signaling in H9c2 cardiomyoblasts.
AB  - Doxorubicin (DOX) is currently used in cancer chemotherapy, however, its use
      often results in adverse effects highlighted by the development of cardiomyopathy
      and ultimately heart failure. Interestingly, DOX cardiotoxicity is decreased by
      resveratrol or by physical activity, suggesting that increased mitochondrial
      activity may be protective. Conversely, recent studies showed that troglitazone,
      a PPARgamma agonist, increases the cytotoxicity of DOX against breast cancer
      cells by up-regulating mitochondrial biogenesis. The hypothesis for the current
      investigation was that DOX cytotoxicity in H9c2 cardiomyoblasts is decreased when
      mitochondrial capacity is increased. We focused on several end-points for DOX
      cytotoxicity, including loss of cell mass, apoptotic signaling and alterations of
      autophagic-related proteins. Our results show that a galactose-based, modified
      cell culture medium increased H9c2 basal mitochondrial respiration, protein
      content, and mtDNA copy number without increasing maximal or spare respiratory
      capacity. H9c2 cardiomyoblasts cultured in the galactose-modified media showed
      lower DOX-induced activation of the apoptotic pathway, measured by decreased
      caspase-3 and -9 activation, and lower p53 expression, although ultimately loss
      of cells was not prevented. Treatment with the PPARgamma agonist troglitazone had
      no effect on DOX toxicity in this cardiac cell line, which agrees with the fact
      that troglitazone did not increase mitochondrial DNA content or capacity at the
      concentrations and duration of exposure used in this investigation. Our results
      show that mitochondrial remodeling caused by stimulating basal rates of oxidative
      phosphorylation decreased DOX-induced apoptotic signaling and increased DOX
      induced autophagy in H9c2 cardiomyoblasts. The differential effect on
      cytotoxicity in cardiac versus breast cancer cell lines suggests a possible
      overall improvement in the clinical efficacy for doxorubicin in treating cancer. 

PMID- 25997896
TI  - Something they never got 'em in the world': the Life and Times of Sabato Rodia's
      Towers in Watts.

PMID- 25997897
TI  - The chicken and egg of anxiety and depression.

PMID- 25997898
TI  - Neurotic depression as the missing link: old wine with a new twist on anxiety and
      major depressive disorder.

PMID- 25997895
TI  - Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory
      Conditions.
AB  - The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 acting via its G
      protein coupled receptor (GPCR) CXCR4 has been implicated in neurogenesis,
      neuromodulation, brain inflammation, HIV-1 encephalopathy and tumor growth. CXCR7
      was identified as an alternate receptor for SDF-1/CXCL12. Characterization of
      CXCR7-deficient mice demonstrated a role for CXCR7 in fetal endothelial biology,
      cardiac development, and B-cell localization. Despite its ligand binding
      properties, CXCR7 does not seem to signal like a conventional GPCR. It has been
      suggested that CXCR7 may not function alone but in combination with CXCR4. Here,
      we investigated the regional localization of CXCR7 receptors in adult mouse brain
      using CXCR7-EGFP transgenic mice. We found that the receptors were expressed in
      various brain regions including olfactory bulb, cerebral cortex, hippocampus,
      subventricular zone (SVZ), hypothalamus and cerebellum. Extensive CXCR7
      expression was associated with cerebral blood vessels. Using cell type specific
      markers, CXCR7 expression was found in neurons, astrocytes and oligodendrocyte
      progenitors. GAD-expressing neurons exhibited CXCR7 expression in the
      hippocampus. Expression of CXCR7 in the dentate gyrus included cells that
      expressed nestin, GFAP and cells that appeared to be immature granule cells. In
      mice with Experimental Autoimmune Encephalomyelitis (EAE), CXCR7 was expressed by
      migrating oligodendrocyte progenitors in the SVZ. We then compared the
      distribution of SDF-1/CXCL12 and CXCR7 using bitransgenic mice expressing both
      CXCR7-EGFP and SDF-1-mRFP. Enhanced expression of SDF-1/CXCL12 and CXCR7 was
      observed in the corpus callosum, SVZ and cerebellum. Overall, the expression of
      CXCR7 in normal and pathological nervous system suggests CXCR4-independent
      functions of SDF-1/CXCL12 mediated through its interaction with CXCR7. 

PMID- 25997899
TI  - Decision making in dissection range of temporal bone: refinements to enlarged
      translabyrinthine approach.
AB  - The aim of the study was to describe the refinements to the classic enlarged
      translabyrinthine approach (ETLA) by modifying the bony dissection range of
      temporal bone and to analyze the main outcomes achieved in a series of vestibular
      schwannoma (VS) cases submitted to microsurgery by ETLA. This was a retrospective
      study of 382 patients who underwent VS surgical removal via ETLA between January
      2001 and December 2012. Among those cases, 332 were via classic ETLA, while 28
      cases were via ETLA with blind sac technique and middle ear eradication and 22
      via transotic approach. Total tumor removal was achieved in 368 cases, whereas
      near total removal in 11 patients and subtotal in 3 patients. In cases of large
      VS (>3 cm) via classic ETLA, good short-term and long-term facial nerve function
      (HB I-II) was gained in 27.8 % (32/115) and 42.6 % (49/115) cases, respectively,
      meanwhile in VS operated via blind sac technique, good short-term (p = 0.048) and
      long-term (p = 0.044) facial nerve function was reached in 44.0 % (22/50) and
      60.0 % (30/50) cases, respectively. Postoperative facial nerve function was
      proved to be better in modified ETLA group. CSF leakage occurred in 16 (4.2 %)
      patients via classic ETLA. In 115 cases of large VS (>3 cm), postoperative CSF
      leakage occurred in 10 (8.7 %) patients. Whereas in 50 cases via blind sac
      technique, none developed CSF leakage (p = 0.03). The incidence of CSF leakage
      was lower in modified ETLA group. Our refinements to classic ETLA by changing the
      temporal bone resection range provide a wide surgical field, well prevention of
      CSF leakage and preservation of facial nerve function in large VS.

PMID- 25997900
TI  - Botulinum Toxin A in Clinical Practice, the Technical Aspects and What Urologists
      Want to Know about It.
AB  - OBJECTIVES: To give an overview of the literature concerning the clinical
      practice of Botulinum toxin A (BTA) treatment to meet the needs and knowledge of
      urologists. METHODS: A literature search was performed to BTA treatment, together
      with a survey among Dutch urologist. RESULTS: The registration trials used strict
      inclusion and exclusion criteria, a standardized application technique and follow
      up. The approval for BTA is based on these trials but differs from country to
      country. BTA was already used before these approvals, with different application
      techniques. Published manuscripts about application techniques (trigone
      sparing/suburothelial injections/intradetrusor injections) show different
      outcomes. In literature there is no positive or negative predictor found with a
      preoperatively urodynamic investigation. It is shown that retreatment does not
      cause inflammatory infiltration or fibrosis in the bladder wall. The survey
      showed that in 96% of the urology departments BTA is used. Urodynamic
      investigation is requested by 87% of urologists before the treatment. Although it
      is regarded as an easy-to-learn procedure 60% of urologists would like training
      in practical aspects. CONCLUSIONS: No firm data exist about the technique of
      application with consequently the most optimal results. BTA treatment is regarded
      as an easy-to-learn, but still there is a request for training in practical
      treatment aspects.

PMID- 25997901
TI  - EAO Supplement Working Group 4 - EAO CC 2015 Short implants versus sinus lifting
      with longer implants to restore the posterior maxilla: a systematic review.
AB  - OBJECTIVE: To compare short implants in the posterior maxilla to longer implants
      placed after or simultaneously with sinus floor elevation procedures. The focused
      question was as follows: Are short implants superior to longer implants in the
      augmented sinus in terms of survival and complication rates of implants and
      reconstructions, patient-reported outcome measures (PROMs) and costs? METHODS: A
      MEDLINE search (1990-2014) was performed for randomized controlled clinical
      studies comparing short implants (<=8 mm) to longer implants (>8 mm) in augmented
      sinus. The search was complimented by an additional hand search of the selected
      papers and reviews published between 2011 and 2014. Eligible studies were
      selected based on the inclusion criteria, and quality assessments were conducted.
      Descriptive statistics were applied for a number of outcome measures. Survival
      rates of dental implants were pooled simply in case of comparable studies.
      RESULTS: Eight randomized controlled clinical trials (RCTs) comparing short
      implants versus longer implants in the augmented sinus derived from an initial
      search count of 851 titles were selected and data extracted. In general, all
      studies were well conducted with a low risk of bias for the majority of the
      analyzed parameters. Based on the pooled analyses of longer follow-ups (5
      studies, 16-18 months), the survival rate of longer implants amounted to 99.5%
      (95% CI: 97.6-99.98%) and for shorter implants to 99.0% (95% CI: 96.4-99.8%). For
      shorter follow-ups (3 studies, 8-9 months), the survival rates of longer implants
      are 100% (95% CI: 97.1-100%) and for shorter implants 98.2% (95% CI: 93.9-99.7%).
      Complications were predominantly of biological origin, mainly occurred
      intraoperatively as membrane perforations, and were almost three times as higher
      for longer implant in the augmented sinus compared to shorter implants. PROMs,
      morbidity, surgical time and costs were generally in favor of shorter dental
      implants. All studies were performed by surgeons in specialized clinical
      settings. CONCLUSIONS: The outcomes of the survey analyses demonstrated
      predictably high implant survival rates for short implants and longer implants
      placed in augmented sinus and their respective reconstructions. Given the higher
      number of biological complications, increased morbidity, costs and surgical time
      of longer dental implants in the augmented sinus, shorter dental implants may
      represent the preferred treatment alternative.

PMID- 25997902
TI  - Provision of Personal Healthcare Services by Local Health Departments: 2008-2013.
AB  - INTRODUCTION: The scope of local health department (LHD) involvement in providing
      personal healthcare services versus population-based services has been debated
      for decades. A 2012 IOM report suggests that LHDs should gradually withdraw from
      providing personal healthcare services. The purpose of this study is to assess
      the level of LHD involvement in provision of personal healthcare services during
      2008-2013 and examine the association between provision of personal healthcare
      services and per capita public health expenditures. METHODS: Data are from the
      2013 survey of LHDs and Area Health Resource Files. The number, ratio, and share
      of revenue from personal healthcare services were estimated. Both linear and
      panel fixed effects models were used to examine the association between provision
      of personal healthcare services and per capita public health expenditures. Data
      were analyzed in 2014. RESULTS: The mean number of personal healthcare services
      provided by LHDs did not change significantly in 2008-2013. Overall, personal
      services constituted 28% of total service items. The share of revenue from
      personal services increased from 16.8% in 2008 to 20.3% in 2013. Results from the
      fixed effect panel models show a positive association between personal healthcare
      services' share of revenue and per capita expenditures (b=0.57, p<0.001).
      CONCLUSIONS: A lower share of revenue from personal healthcare services is
      associated with lower per capita expenditures. LHDs, especially those serving
      <25,000 people, are highly dependent on personal healthcare revenue to sustain
      per capita expenditures. LHDs may need to consider strategies to replace lost
      revenue from discontinuing provision of personal healthcare services.

PMID- 25997904
TI  - Health Center Patients' Insurance Status and Healthcare Use Prior to
      Implementation of the Affordable Care Act.
AB  - INTRODUCTION: U.S. health centers provide primary and preventive care to
      underserved populations, including low-income and uninsured patients. The purpose
      of this study is to examine patterns of publicly funded health center use
      according to patient insurance status (private, public, none), prior to
      implementation of the Affordable Care Act. METHODS: National data came from the
      2009 Health Center Patient Survey, and were analyzed in 2013. Descriptive
      analysis of health center patient insurance coverage and health center
      utilization variables was conducted, followed by adjusted multivariate analysis.
      RESULTS: About 91% of uninsured patients received at least half their annual
      healthcare visits at a health center, and 86% had at least one usual source of
      care that included a health center; these rates were not significantly different
      from those for publicly or privately insured patients. About half of uninsured
      patients (48%) had long tenures at the health center (>=3 years since first
      visit), not significantly different from the publicly insured (52%), but lower
      than the privately insured (63%, p<0.01). Uninsured patients highlighted
      affordability as the main reason for visiting a health center, whereas insured
      patients emphasized convenient location and quality of care. CONCLUSIONS: Insured
      patients used health centers for the majority of their care, and in similar
      proportions to their uninsured counterparts. The primary motivation for visiting
      a health center differed based on insurance type. Future studies should be able
      to examine whether health center demand across insurance categories follows a
      similar pattern following the Affordable Care Act insurance coverage expansions.

PMID- 25997903
TI  - Self-Reported Mental Disorders and Distress by Sexual Orientation: Results of the
      Minnesota College Student Health Survey.
AB  - INTRODUCTION: Sexual minority college students (i.e., those not identifying as
      heterosexual, or those reporting same-sex sexual activity) may be at increased
      risk of poor mental health, given factors such as minority stress, stigma, and
      discrimination. Such disparities could have important implications for students'
      academic achievement, future health, and social functioning. This study compares
      reports of mental disorder diagnoses, stressful life events, and frequent mental
      distress across five gender-stratified sexual orientation categories. METHODS:
      Data were from the 2007-2011 College Student Health Survey, which surveyed a
      random sample of college students (N=34,324) at 40 Minnesota institutions. Data
      analysis was conducted in 2013-2014. The prevalence of mental disorder diagnoses,
      frequent mental distress, and stressful life events were calculated for
      heterosexual, discordant heterosexual, gay or lesbian, bisexual, and unsure
      students. Logistic regression models were fit to estimate the association between
      sexual orientation and mental health outcomes. RESULTS: Lesbian, gay, and
      bisexual students were more likely to report any mental health disorder diagnosis
      than were heterosexual students (p<0.05). Lesbian, gay, bisexual, and unsure
      students were significantly more likely to report frequent mental distress
      compared to heterosexual students (OR range, 1.6-2.7). All sexual minority
      groups, with the exception of unsure men, had significantly greater odds of
      experiencing two or more stressful life events (OR range, 1.3-2.8). CONCLUSIONS:
      Sexual minority college students experience worse mental health than their
      heterosexual peers. These students may benefit from interventions that target the
      structural and social causes of these disparities, and individual-level
      interventions that consider their unique life experiences.

PMID- 25997905
TI  - Pre-screening Discussions and Prostate-Specific Antigen Testing for Prostate
      Cancer Screening.
AB  - INTRODUCTION: For many men, the net benefit of prostate cancer screening with
      prostate-specific antigen (PSA) tests may be small. Many major medical
      organizations have issued recommendations for prostate cancer screening,
      stressing the need for shared decision making before ordering a test. The purpose
      of this study is to better understand associations between discussions about
      benefits and harms of PSA testing and uptake of the test among men aged >=40
      years. METHODS: Associations between pre-screening discussions and PSA testing
      were examined using self-reported data from the 2012 Behavioral Risk Factor
      Surveillance System. Unadjusted prevalence of PSA testing was estimated and AORs
      were calculated using logistic regression in 2014. RESULTS: The multivariate
      analysis showed that men who had ever discussed advantages of PSA testing only or
      discussed both advantages and disadvantages were more likely, respectively, to
      report having had a test within the past year than men who had no discussions
      (p<0.001). In addition, men who had only discussed the disadvantages of PSA
      testing with their healthcare providers were more likely (AOR=2.75, 95% CI=2.00,
      3.79) to report getting tested than men who had no discussions. CONCLUSIONS:
      Discussions of the benefits or harms of PSA testing are positively associated
      with increased uptake of the test. Given the conflicting recommendations for
      prostate cancer screening and increasing importance of shared decision making,
      this study points to the need for understanding how pre-screening discussions are
      being conducted in clinical practice and the role played by patients' values and
      preferences in decisions about PSA testing.

PMID- 25997906
TI  - Effect of Uruguay's National 100% Smokefree Law on Emergency Visits for
      Bronchospasm.
AB  - INTRODUCTION: Implementation of smokefree laws is followed by drops in hospital
      admissions for cardiovascular diseases and asthma. The impact of smokefree laws
      on use of non-hospital medical services has not been assessed. The purpose of
      this study is to evaluate the impact of Uruguay's national 100% smokefree
      legislation on non-hospital emergency care visits, hospitalizations for
      bronchospasm, and bronchodilator use. METHODS: The monthly number of non-hospital
      emergency care visits and hospitalizations for bronchospasm, as well as monthly
      puffs of bronchodilators (total and per person), from 3 years prior to the
      adoption of the 100% smokefree policy on March 1, 2006, through 5 years after the
      policy were assessed using interrupted time series negative binomial regression.
      Data analysis was conducted in 2014. RESULTS: The incidence of non-hospital
      emergency visits for bronchospasm decreased by 15% (incidence rate ratio
      [IRR]=0.85, 95% CI=0.76, 0.94) following implementation of the law.
      Hospitalizations for bronchospasm did not change significantly (IRR=0.89, 95%
      CI=0.66, 1.21). Total monthly puffs of salbutamol and ipratropium administered in
      the non-hospital emergency setting decreased by 224 (95% CI=-372, -76) and 179
      (95% CI=-340, -18.6), respectively, from means of 1,222 and 1,007 before the law.
      CONCLUSIONS: Uruguay's 100% smokefree law was followed by fewer emergency visits
      for bronchospasm and less need for treatment, supporting adoption of such
      policies in low- and middle-income countries to reduce the disease burden and
      healthcare costs associated with smoking.

PMID- 25997907
TI  - Are We Asking Patients if They Smoke?: Missing Information on Tobacco Use in
      Canadian Electronic Medical Records.
AB  - INTRODUCTION: All adolescent and adult patients should be asked if they smoke.
      Data entered in electronic medical records offer new opportunities to study
      tobacco-related clinical activities. The purpose of this study is to examine the
      recording of tobacco use in Canadian electronic medical records. METHODS: Data
      were collected on September 30, 2013, and analyzed in 2014. Data on 249,223
      patients that were aged >=16 years as of September 30, 2013 and had at least one
      primary care encounter in the previous 2 years were included. The proportion of
      patients with information on tobacco use entered in a summative health profile
      was calculated. Associations between data gaps and patient or physician factors
      were examined. RESULTS: Information on tobacco use was available for 64.4% of
      patients. Physicians using an electronic medical record for >=4 years were more
      likely to have data (AOR=4.57, 95% CI=1.84, 7.29, p<0.0001). Patients aged >=30
      years were more likely to have tobacco information present (AOR=2.92, 95%
      CI=2.82, 3.02, p<0.0001, for patients aged 30-59 compared to those aged <30
      years), as were patients with any comorbidities (AOR=1.41, 95% CI=1.36, 1.45,
      p<0.0001, for patients with one or two comorbidities compared with none) or more
      visits. CONCLUSIONS: A third of Canadians in this sample lacked data on tobacco
      in their electronic medical record. Younger, healthier people were less likely to
      have information about their smoking status. Efforts to improve the recording of
      tobacco-related information in electronic medical records, especially for younger
      patients, are needed.

PMID- 25997908
TI  - Distinct effects of perinatal exposure to fluoxetine or methylmercury on
      parvalbumin and perineuronal nets, the markers of critical periods in brain
      development.
AB  - The in utero exposure to common chemical stressors, environmental pollutant
      methylmercury and antidepressant fluoxetine, results in behavioral impairments
      persistent into adulthood. Modulation of critical periods in brain development
      may alter proper network formation and lastingly impair brain function. To
      investigate whether early-life stressors can modulate critical periods, we
      analyzed the development of parvalbumin (PV) and perineuronal nets (PNNs) in the
      dentate gyrus and CA1 area of the hippocampus and the basolateral amygdala in
      mice perinatally exposed to either fluoxetine or methylmercury. The number of PV
      and PNN neurons, and PV intensity, were analyzed by fluorescent
      immunohistochemistry at the postnatal ages P17 (ongoing critical period) and P24
      (closing critical period). The exposure to fluoxetine did not affect the number
      of PV cells and PV intensity but decreased PNN formation around the cells at P17
      and P24 in all tissues. In contrast, perinatal methylmercury inhibited the
      development of PV interneurons and PV expression at P17 only, but at P24 these
      parameters were restored. Methylmercury strongly increased PNN formation from P17
      to P24 in the amygdala only. We suggest that perinatal fluoxetine and
      methylmercury might delay the closure and the onset, respectively, of the
      critical periods in the amygdala and hippocampus. 

PMID- 25997909
TI  - Astrocytic beta1-integrin affects cellular composition of murine blood brain
      barrier in the cerebral cortex.
AB  - The blood brain barrier (BBB) is composed of endothelial cells, astrocytes, and
      pericytes and maintains functional homeostasis by regulating transport of ions,
      fluid and cells between blood and neural tissue. The cellular and molecular
      pathways that contribute to the formation of the BBB in the developing brain have
      not been fully deciphered. beta1-integrin (beta1-itg) within endothelial cells is
      known to play a critical role in vasculogenesis. However, the role of astrocytic
      beta1-itg in BBB development is not known. Our study used a mouse glial
      fibrillary acidic protein (GFAP)-cre transgenic line to selectively ablate beta1
      itg within astrocytes. We found that deletion of astrocytic beta1-itg had a
      striking effect on the different cell types that form the BBB. Mutant mice had a
      decreased density of aquaporin-4 immunoreactivity within the perivascular
      astrocytic end-feet. We also found decreases in immunoreactivity for vimentin and
      CD-31 within endothelial cells. These changes were not accompanied by functional
      changes in BBB under physiological conditions as assessed by extravasation of
      large and small molecular weight molecules. However, mutant mice had an increased
      incidence of severe cystic injury in response to neonatal hypoxia. Our findings
      show that astrocytic beta1-itg has an important role in defining cellular
      properties of the blood brain barrier in the cerebral cortex. 

PMID- 25997910
TI  - Intrafamilial clinical heterogeneity of CSPP1-related ciliopathy.

PMID- 25997911
TI  - Commentary on Nath and Villadsen review entitled "Oxidative phosphorylation
      revisited" Biotechnol. Bioeng. 112 (2015) 429-437.

PMID- 25997912
TI  - Early Seizure Detection Using Neuronal Potential Similarity: A Generalized Low
      Complexity and Robust Measure.
AB  - A novel approach using neuronal potential similarity (NPS) of two intracranial
      electroencephalogram (iEEG) electrodes placed over the foci is proposed for
      automated early seizure detection in patients with refractory partial epilepsy.
      The NPS measure is obtained from the spectral analysis of space-differential iEEG
      signals. Ratio between the NPS values obtained from two specific frequency bands
      is then investigated as a robust generalized measure, and reveals invaluable
      information about seizure initiation trends. A threshold-based classifier is
      subsequently applied on the proposed measure to generate alarms. The performance
      of the method was evaluated using cross-validation on a large clinical dataset,
      involving 183 seizure onsets in 1785 h of long-term continuous iEEG recordings of
      11 patients. On average, the results show a high sensitivity of 86.9% (159 out of
      183), a very low false detection rate of 1.4 per day, and a mean detection
      latency of 13.1 s from electrographic seizure onsets, while in average preceding
      clinical onsets by 6.3 s. These high performance results, specifically the short
      detection latency, coupled with the very low computational cost of the proposed
      method make it adequate for using in implantable closed-loop seizure suppression
      systems. 

PMID- 25997913
TI  - Self-assembly of dynamic orthoester cryptates.
AB  - The discovery of coronands and cryptands, organic compounds that can accommodate
      metal ions in a preorganized two- or three-dimensional environment, was a
      milestone in supramolecular chemistry, leading to countless applications from
      organic synthesis to metallurgy and medicine. These compounds are typically
      prepared via multistep organic synthesis and one of their characteristic features
      is the high stability of their covalent framework. Here we report the use of a
      dynamic covalent exchange reaction for the one-pot template synthesis of a new
      class of coronates and cryptates, in which acid-labile O,O,O-orthoesters serve as
      bridgeheads. In contrast to their classic analogues, the compounds described
      herein are constitutionally dynamic in the presence of acid and can be induced to
      release their guest via irreversible deconstruction of the cage. These properties
      open up a wide range of application opportunities, from systems chemistry to
      molecular sensing and drug delivery. 

PMID- 25997914
TI  - Transcriptional Activity and DNA Methylation Dynamics of the Gal4/UAS System in
      Zebrafish.
AB  - The Gal4/upstream activating sequence (UAS) system is a powerful genetic tool for
      the temporal and spatial expression of target genes. In this study, the dynamic
      activity of the Gal4/UAS system was monitored in zebrafish throughout the entire
      lifespan and during germline transmission, using an optimized Gal4/UAS,
      KalTA4/4xUAS, which is driven by two muscle-specific regulatory sequences. We
      found that UAS-linked gene expression was transcriptionally amplified by Gal4/UAS
      during early developmental stages and that the amplification effects tended to
      weaken during later stages and even disappear in subsequent generations. In the
      F2 generation, the transcription of a UAS-linked enhanced green fluorescent
      protein (EGFP) reporter was transcriptionally silent from 16 days post
      fertilization (dpf) into adulthood, yet offspring of this generation showed
      reactivation of the EGFP reporter in some strains. We further show that the
      transcriptional silencing and reactivation of UAS-driven EGFP correlated with the
      DNA methylation levels of the UAS regulatory sequences. Notably, asymmetric DNA
      methylation of the 4xUAS occurred in oocytes and sperm. Moreover, the paternal
      and maternal 4xUAS sequences underwent different DNA methylation dynamics after
      fertilization. Our study suggests that the Gal4/UAS system may represent a
      powerful tool for tracing the DNA methylation dynamics of paternal and maternal
      loci during zebrafish development and that UAS-specific DNA methylation should be
      seriously considered when the Gal4/UAS system is applied in zebrafish. 

PMID- 25997915
TI  - Isolation and phenotypic characterization of cancer stem-like side population
      cells in colon cancer.
AB  - Previous studies in cancer biology suggest that chemotherapeutic drug resistance
      and tumor relapse are driven by cells within a tumor termed 'cancer stem cells'.
      In the present study, a Hoechst 33342 dye exclusion technique was used to
      identify cancer stem-like side population (SP) cells in colon carcinoma, which
      accounted for 3.4% of the total cell population. Following treatment with
      verapamil, the population of SP cells was reduced to 0.6%. In addition, the
      sorted SP cells exhibited marked multidrug resistance and enhanced cell survival
      rates compared with non-SP cells. The SP cells were able to generate more tumor
      spheres and were CD133 positive. Subsequent biochemical analysis revealed that
      the levels of the adenosine triphosphate-binding cassette sub-family G member 2
      transporter protein, B-cell lymphoma anti-apoptotic factor and autocrine
      production of interleukin-4 were significantly enhanced in the colon cancer SP
      cells, which contributed to drug resistance, protection of the cells from
      apoptosis and tumor recurrence. Therefore, the findings suggested that treatment
      failure and colon tumorigenesis is dictated by a small population of SP cells,
      which indicate a potential target in future therapies. 

PMID- 25997916
TI  - The Impact of PBRM1 Expression as a Prognostic and Predictive Marker in
      Metastatic Renal Cell Carcinoma.
AB  - PURPOSE: PBRM1, a SWI/SNF chromatin remodeling complex gene, is the second most
      frequently mutated gene in clear cell renal cell carcinoma. Although previous
      studies showed that loss of PBRM1 expression was associated with poor prognosis
      of renal cell carcinoma, these studies were performed on earlier stage,
      surgically resected renal cell carcinoma. Accordingly we investigated the PBRM1
      expression profile in patients with stage IV renal cell carcinoma to determine
      the prognostic and predictive value of PBRM1. MATERIALS AND METHODS: A total of
      53 patients with stage IV or recurrent renal cell carcinoma were included in
      analysis. Immunohistochemistry was performed for PBRM1 using formalin fixed,
      paraffin embedded tissue microarrays. RESULTS: Overall 25 of 53 patients (47%)
      had high PBRM1 expression in the tumor. On analysis comparing survival rates and
      treatment responses of patients with renal cell carcinoma high PBRM1 expression
      in the tumor was associated with reduced overall survival (mean +/- SD 45.0 +/-
      4.8 vs 23.0 +/- 8.3 months, p = 0.022, and for clear cell renal cell carcinoma
      46.0 +/- 4.1 vs 27.0 +/- 6.7 months, p = 0.053). Regarding treatment outcome
      higher PBRM1 expression tended to indicate a poorer response to mTOR inhibitor
      (median progression-free survival 3.0 +/- 0.2 vs 1.9 +/- 2.3 months, p = 0.101).
      On subgroup analysis according to the Heng score this trend was more significant
      in the higher risk group than in the low risk group (progression-free survival
      for low risk mean 11.6 +/- 1.2 vs 7.4 +/- 7.4 months, p = 0.157, and for
      intermediate risk 7.1 +/- 24.7 vs 2.9 +/- 0.9 months, p = 0.060). CONCLUSIONS:
      Our study shows that the PBRM1 expression level is a potential prognostic marker
      for advanced renal cell carcinoma. We suggest that determining the tumor PBRM1
      expression level may be used to inform the prognosis and treatment of metastatic
      renal cell carcinoma.

PMID- 25997917
TI  - Enhanced multi-colour gating for the generation of high-power isolated attosecond
      pulses.
AB  - Isolated attosecond pulses (IAP) generated by high-order harmonic generation are
      valuable tools that enable dynamics to be studied on the attosecond time scale.
      The applicability of these IAP would be widened drastically by increasing their
      energy. Here we analyze the potential of using multi-colour driving pulses for
      temporally gating the attosecond pulse generation process. We devise how this
      approach can enable the generation of IAP with the available high-energy kHz
      repetition-rate Ytterbium-based laser amplifiers (delivering 180-fs, 1030-nm
      pulses). We show theoretically that this requires a three-colour field composed
      of the fundamental and its second harmonic as well as a lower-frequency auxiliary
      component. We present pulse characterization measurements of such auxiliary
      pulses generated directly by white-light seeded OPA with the required
      significantly shorter pulse duration than that of the fundamental. This, combined
      with our recent experimental results on three-colour waveform synthesis, proves
      that the theoretically considered multi-colour drivers for IAP generation can be
      realized with existing high-power laser technology. The high-energy driver
      pulses, combined with the strongly enhanced single-atom-level conversion
      efficiency we observe in our calculations, thus make multi-colour drivers prime
      candidates for the development of unprecedented high-energy IAP sources in the
      near future. 

PMID- 25997918
TI  - Emotion regulation in bipolar disorder type I: an fMRI study.
AB  - BACKGROUND: Bipolar disorder type I (BD-I) is associated with emotion
      dysregulation. However, experimentally controlled studies of emotion regulation
      (ER), particularly those examining the brain correlates of the putative deficits,
      are scarce and their results inconsistent. METHOD: Nineteen euthymic BD-I
      patients and 17 healthy controls (HC) underwent functional magnetic resonance
      imaging while performing a visual ER 2 * 2 factorial task, with instruction (Look
      or Decrease) and valence (Negative or Neutral) as within-subject factors.
      Emotional ratings were collected after each picture presentation to assess
      regulation success. RESULTS: BD-I patients were successful at downregulating
      their emotions, although to a lesser degree than HC. Both groups engaged brain
      regions previously implicated in ER; however, unlike HC, patients engaged some of
      those regions, particularly the ventrolateral prefrontal cortex (VLPFC) in the
      Negative Look and Neutral Decrease conditions. Moreover, patients failed to show
      the reduced amygdala activation in the Negative Decrease condition observed in
      HC. CONCLUSION: Our findings suggest that BD-I patients are able to downregulate
      their emotions when instructed to do so. However, they also appear to engage
      their ER network, particularly the VLPFC, even when not required to do so. These
      findings may help explain their often-reported difficulty in regulating emotions
      in everyday life despite their attempts to do so.

PMID- 25997919
TI  - Gnathostomiasis: An Emerging Infection of Raw Fish Consumers in Gnathostoma
      Nematode-Endemic and Nonendemic Countries.
AB  - BACKGROUND: Gnathostomiasis, a helminthic infection commonly reported in
      Southeast Asia and Latin America, may follow consumption of raw seafood infected
      with muscle-encysted larvae of Gnathostoma species nematodes. As a result of
      increasingly exotic tastes for local ethnic dishes, including raw seafood, some
      regions outside of gnathostome-endemic areas import live species for raw
      consumption. This may facilitate imported human gnathostomiasis or potentially
      the establishment of this zoonosis in formerly nonendemic regions. Traveling to a
      gnathostome-endemic area is no longer a criterion for diagnosis. The objectives
      of this review are to enhance clinician awareness of this infection by describing
      the behavioral risk factors for its acquisition, life-cycle, clinical
      manifestations, diagnosis, management, and prevention. METHODS: Internet search
      engines were queried with the key medical subject heading words. Case reports,
      case series, epidemiological investigations, and laboratory studies were
      reviewed; high risk behaviors for gnathostomiasis were identified; and human
      cases were stratified as cutaneous gnathostomiasis, visceral gnathostomiasis,
      neurognathostomiasis, and ocular gnathostomiasis. RESULTS: The greatest risk
      factors for gnathostomiasis included the consumption of raw freshwater seafood
      dishes in endemic regions and the consumption of raw imported or domestic seafood
      dishes in households and ethnic restaurants in many nonendemic regions.
      CONCLUSIONS: Gnathostomiasis is no longer a disease of returning travelers, and
      autochthonous cases may be anticipated to increase as a result of the importation
      of live Gnathostoma-infected species and the potential establishment of regional
      zoonoses of Gnathostoma-infected wild species. Since the eradication of
      gnathostomiasis is unlikely given the global distribution of Gnathostoma
      nematodes, the only effective preventive strategy is to educate persons in
      endemic and nonendemic areas that fish, eels, frogs, snakes, and birds must be
      cooked thoroughly first before eating and not eaten raw or marinated. The onset
      of migratory subcutaneous swellings with hyper-eosinophilia weeks to months after
      consuming raw seafood should provoke suspicion of gnathostomiasis.

PMID- 25997920
TI  - Mapping Functions in Health-Related Quality of Life: Mapping from Two Cancer
      Specific Health-Related Quality-of-Life Instruments to EQ-5D-3L.
AB  - BACKGROUND: Clinical trials in cancer frequently include cancer-specific measures
      of health but not preference-based measures such as the EQ-5D that are suitable
      for economic evaluation. Mapping functions have been developed to predict EQ-5D
      values from these measures, but there is considerable uncertainty about the most
      appropriate model to use, and many existing models are poor at predicting EQ-5D
      values. This study aims to investigate a range of potential models to develop
      mapping functions from 2 widely used cancer-specific measures (FACT-G and EORTC
      QLQ-C30) and to identify the best model. METHODS: Mapping models are fitted to
      predict EQ-5D-3L values using ordinary least squares (OLS), tobit, 2-part models,
      splining, and to EQ-5D item-level responses using response mapping from the FACT
      G and QLQ-C30. A variety of model specifications are estimated. Model performance
      and predictive ability are compared. Analysis is based on 530 patients with
      various cancers for the FACT-G and 771 patients with multiple myeloma, breast
      cancer, and lung cancer for the QLQ-C30. RESULTS: For FACT-G, OLS models most
      accurately predict mean EQ-5D values with the best predicting model using FACT-G
      items with similar results using tobit. Response mapping has low predictive
      ability. In contrast, for the QLQ-C30, response mapping has the most accurate
      predictions using QLQ-C30 dimensions. The QLQ-C30 has better predicted EQ-5D
      values across the range of possible values; however, few respondents in the FACT
      G data set have low EQ-5D values, which reduces the accuracy at the severe end.
      CONCLUSIONS: OLS and tobit mapping functions perform well for both instruments.
      Response mapping gives the best model predictions for QLQ-C30. The
      generalizability of the FACT-G mapping function is limited to populations in
      moderate to good health.

PMID- 25997922
TI  - Atorvastatin Attenuates Bone Loss and Aortic Valve Atheroma in LDLR Mice.
AB  - Atherosclerosis and osteoporosis are the leading causes of mortality and
      morbidity. The objective of this study was to test this hypothesis in
      experimental hypercholesterolemia to determine whether statins play a protective
      role in this process. LDLR(-/-) mice (n = 60) were allocated to the following
      groups: group I (n = 20), normal diet; group II (n = 20), 0.25% (w/w) cholesterol
      diet (w/w), and group III (n = 20), 0.25% (w/w) cholesterol diet + atorvastatin
      for 48 weeks. Examination of aortic valves (AVA) and femurs for atherosclerosis
      and calcification markers included micro-CT, special stains, and calcein
      incorporation. The cholesterol diet induced bone formation in calcified AVA and
      an increase in macrophage infiltration. Hyperlipidemic bones expressed an
      increase in osteoclast cells and a decrease in bone formation. Atorvastatin
      reduced atherosclerosis and bone mineralization in AVA and increased
      mineralization within femur bones (p < 0.05). Atherosclerosis is present in
      hyperlipidemic bones and valves as characterized by macrophage and osteoclast
      infiltration, and it is attenuated by atorvastatin, which may have implications
      for therapy in the future.

PMID- 25997921
TI  - Retinoids induce cellular senescence in breast cancer cells by RAR-beta dependent
      and independent pathways: Potential clinical implications (Review).
AB  - Most studies on cellular senescence (CS) have been performed in vitro by
      employing cytotoxic agents, irradiation, chromatin and telomerase modulators or
      by activating certain oncogenes. All these approaches usually lead to DNA damage,
      gene instability and/or chromatin alterations that primarily affect p53-p21
      signaling. Little is known on whether retinoids and rexinoids, which are cell
      differentiation agents, can also induce CS in vitro and in vivo, and which
      molecular mechanisms are involved in promoting the senescent phenotype. We
      reviewed the recent publications on CS induced by retinoids and rexinoids in ER+
      and ER- breast cancer cell lines and in corresponding animal models of mammary
      carcinogenesis which simulate those of human breast cancer. The role of retinoic
      acid receptors beta2 and 5 (RARbeta2 and RARbeta5) and of receptor independent
      genes involved in mediating the senescence program of retinoids and rexinoids in
      ER+ and ER- breast cancer cells is discussed. Potential strategists for clinical
      implication of CS as biomarker of prognosis and of response to treatment with
      retinoids, rexinoids and with other cell differentiation and antitumor agents are
      outlined.

PMID- 25997924
TI  - Are mirror-sensations really synesthetic?
AB  - Mirror-sensations, including touch and pain, are often referred to as
      synesthetic. The term can be challenged, however, because mirror-sensations lack
      the incongruency and saliency of synesthesia, may involve problems of perspective
      rather than entangled sensations, and may be easier to generate with suggestion.
      If mirror-sensations are truly sensations then they might be expected to act like
      the true sensation and mirror-pain, for example, might inhibit pain at a distance
      or itch in the same location. These predictions are highly testable. 

PMID- 25997923
TI  - HIV with non-communicable diseases in primary care in Kibera, Nairobi, Kenya:
      characteristics and outcomes 2010-2013.
AB  - BACKGROUND: Antiretroviral therapy (ART) has increased the life expectancy of
      people living with HIV (PLHIV); HIV is now considered a chronic disease. Non
      communicable diseases (NCDs) and HIV care were integrated into primary care
      clinics operated within the informal settlement of Kibera, Nairobi, Kenya. We
      describe early cohort outcomes among PLHIV and HIV-negative patients, both of
      whom had NCDs. METHODS: A retrospective analysis was performed of routinely
      collected clinic data from January 2010 to June 2013. All patients >14 years with
      hypertension and/or diabetes were included. RESULTS: Of 2206 patients included in
      the analysis, 210 (9.5%) were PLHIV. Median age at enrollment in the NCD program
      was 43 years for PLHIV and 49 years for HIV-negative patients (p<0.0001). The
      median duration of follow up was 1.4 (IQR 0.7-2.1) and 1.0 (IQR 0.4-1.8) years
      for PLHIV and HIV-negative patients, respectively (p=0.003). Among patients with
      hypertension, blood pressure outcomes were similar, and for those with diabetes,
      outcomes for HbA1c, fasting glucose and cholesterol were not significantly
      different between the two groups. The frequency of chronic kidney disease (CKD)
      was 12% overall. Median age for PLHIV and CKD was 50 vs 55 years for those
      without HIV (p=0.005). CONCLUSIONS: In this early comparison of PLHIV and HIV
      negative patients with NCDs, there were significant differences in age at
      diagnosis but both groups responded similarly to treatment. This study suggests
      that integrating NCD care for PLHIV along with HIV-negative patients is feasible
      and achieves similar results.

PMID- 25997925
TI  - The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and
      Acute Coronary Syndromes.
AB  - The inflammation underlying both atherosclerosis and acute coronary syndromes is
      strongly related to monocyte-related actions. However, different monocyte subsets
      can play differential roles in the formation and destabilization of
      atherosclerotic plaque as well as healing of damaged myocardial tissue. Monocytes
      are currently being divided into three functionally distinct subsets with
      different levels of CD14 (cluster of differentiation 14) and CD16 expression.
      Thus, there are classical CD14++CD16-, intermediate CD14++CD16+ and non-classical
      CD14+CD16++ monocytes. Here, we summarize the current knowledge on complex
      activities of different monocyte subsets in atherosclerosis and acute coronary
      syndromes. Moreover, we discuss which monocyte subsets can serve either as
      predictive biomarkers of cardiovascular risk or as potential targets used in
      atherosclerosis and its complications. 

PMID- 25997926
TI  - Robot-assisted laparoscopic hiatal hernia and antireflux surgery.
AB  - Gastroesophageal reflux disease is a common disorder of the GE-junction that
      allows gastric acid to enter the esophagus. Surgery is indicated when the
      presence of the disease is objectively documented. The laparoscopic Toupet
      fundoplication is the preferred treatment of GERD. There is no clear advantage in
      robotic assistance for primary antireflux surgery. In our center we find the
      robot to be of added value for redo surgery or large and giant hiatal repair.

PMID- 25997927
TI  - Genetic diversity and population structure of beet necrotic yellow vein virus in
      China.
AB  - Beet necrotic yellow vein virus (BNYVV) is a serious threat to the sugar beet
      industry worldwide. However, little information is available regarding the
      genetic diversity and population structure of BNYVV in China. Here, we analyzed
      multiple sequences from four genomic regions (CP, RNA3, RNA4 and RNA5) of a set
      of Chinese isolates. Sequence analyses revealed that several isolates were mixed
      infections of variants with different genotypes and/or different p25 tetrad
      motifs. In total, 12 distinct p25 tetrads were found in the Chinese BNYVV
      population, of which four tetrads were newly identified. Phylogenetic analyses
      based on four genes (CP, RNA3-p25, RNA4-p31 and RNA5-p26) in isolates from around
      the world revealed the existence of two to four groups, which mostly corresponded
      to previously reported phylogenetic groups. Two new subgroups and a new group
      were identified from the Chinese isolates in p25 and p26 trees, respectively.
      Selection pressure analysis indicated that there was a positive selection
      pressure on the p25 from the Chinese isolates, but the other three proteins were
      under a negative selection pressure. There was frequent gene flow between
      geographically distant populations, which meant that BNYVV populations from
      different provinces were not geographically differentiated. 

PMID- 25997928
TI  - Bats as reservoirs of severe emerging infectious diseases.
AB  - In recent years severe infectious diseases have been constantly emerging, causing
      panic in the world. Now we know that many of these terrible diseases are caused
      by viruses originated from bats (Table 1), such as Ebola virus, Marburg, SARS
      coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), Nipah virus (NiV) and Hendra
      virus (HeV). These viruses have co-evolved with bats due to bats' special social,
      biological and immunological features. Although bats are not in close contact
      with humans, spillover of viruses from bats to intermediate animal hosts, such as
      horses, pigs, civets, or non-human primates, is thought to be the most likely
      mode to cause human infection. Humans may also become infected with viruses
      through aerosol by intruding into bat roosting caves or via direct contact with
      bats, such as catching bats or been bitten by bats. 

PMID- 25997929
TI  - Singapore grouper iridovirus (SGIV) encoded SGIV-miR-13 attenuates viral
      infection via modulating major capsid protein expression.
AB  - Singapore grouper iridovirus (SGIV) encodes a number of microRNAs (miRNAs) during
      infection. Among these, SGIV-miR-13 has robust expression at early stage after
      SGIV inoculation, raising a huge possibility that it participates in the viral
      infection. In the present study, we found that SGIV-miR-13 overexpression led to
      a significant reduction in viral load in cultured fish cells with SGIV infection,
      as demonstrated by less level of viral transcripts, viral-induced cytopathic
      effect (CPE) and assembled viral particles. In silico analysis showed that SGIV
      miR-13 maps antisense to the coding region of SGIV major capsid protein (SGIV
      MCP), suggesting it to be a potential target of SGIV-miR-13. Coincidently, SGIV
      miR-13 showed an inverted expression profile with SGIV-MCP during SGIV infection,
      and luciferase reporter assay further demonstrated SGIV-MCP as the direct target
      of SGIV-miR-13. Functionally, overexpression of SGIV-miR-13 inhibited, whereas
      knockdown of SGIV-miR-13 restored the expression of SGIV-MCP during viral
      infection, resulting in altered viral progeny emergences. In conclusion, our data
      suggest that SGIV-miR-13 functions in a negative regulatory mechanism to restrict
      early viral replication, and thus prevents excessive cellular antiviral responses
      during SGIV infection. The detailed investigation of SGIV encoded miRNAs may
      provide new insights into the mechanism of iridovirus pathogenesis. 

PMID- 25997930
TI  - The human papillomavirus18 E7 protein inhibits CENP-C binding to alpha-satellite
      DNA.
AB  - Human papillomavirus (HPV) infection leads to aneuploidy, a numerical chromosomal
      aberration that is caused by dysregulation of chromosomal segregation. We
      previously found that the E7 proteins of high-risk HPVs, but not of low-risk
      HPVs, could bind to centromere protein-C (CENP-C). In this study, we first found
      that CENP-C could bind centromere alpha-satellite DNAs using ChIP analysis and HA
      tagged CENP-C/nuc transfected 293T cells. We then investigated if HA-CENP-C/nuc
      binding to alpha-satellite DNAs was affected by the E7 proteins of high- or low
      risk HPVs. We found that transfection of the FLAG tagged HPV18 E7 inhibited the
      binding of HA-CENP-C/nuc to alpha-satellite DNAs. This finding was confirmed in
      HeLa S3 cells transfected with siRNA targeted to HPV18 E7 expression. We
      therefore speculate that altered function of kinetochores as a result of
      inhibition of CENP-C and alpha-satellite DNAs binding may be associated with the
      chromosomal abnormalities observed in HPV18-positive cancers. 

PMID- 25997933
TI  - Nerve localization techniques for peripheral nerve block and possible future
      directions.
AB  - BACKGROUND: Ultrasound guidance is now a standard nerve localization technique
      for peripheral nerve block (PNB). Ultrasonography allows simultaneous
      visualization of the target nerve, needle, local anesthetic injectate, and
      surrounding anatomical structures. Accurate deposition of local anesthetic next
      to the nerve is essential to the success of the nerve block procedure. Due to
      limitations in the visibility of both needle tip and nerve surface, the precise
      relationship between needle tip and target nerve is unknown at the moment of
      injection. Importantly, nerve injury may result both from an inappropriately
      placed needle tip and inappropriately placed local anesthetic. The relationship
      between the block needle tip and target nerve is of paramount importance to the
      safe conduct of peripheral nerve block. METHODS: This review summarizes the
      evolution of nerve localization in regional anesthesia, characterizes a problem
      faced by clinicians in performing ultrasound-guided nerve block, and explores the
      potential technological solutions to this problem. RESULTS: To date, technology
      newly applied to PNB includes real-time 3D imaging, multi-planar magnetic needle
      guidance, and in-line injection pressure monitoring. This review postulates that
      optical reflectance spectroscopy and bioimpedance may allow for accurate
      identification of the relationship between needle tip and target nerve, currently
      a high priority deficit in PNB techniques. CONCLUSIONS: Until it is known how
      best to define the relationship between needle and nerve at the moment of
      injection, some common sense principles are suggested.

PMID- 25997931
TI  - PTK7+ Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization
      by Upregulating Angiopoietin-1.
AB  - OBJECTIVE: In angiogenesis, circulating mononuclear cells are recruited to
      vascular lesions; however, the underlying mechanisms are poorly understood.
      APPROACH AND RESULTS: Here, we characterize the functional role of protein
      tyrosine kinase 7 (PTK7)-expressing CD11b(+) mononuclear cells in vitro and in
      vivo using a mouse model of angiogenesis. Although the frequencies of
      PTK7(+)CD11b(+) cells in the bone marrow remained similar after vascular
      endothelial growth factor-A-induced neovascularization, we observed an 11-fold
      increase in the cornea. Importantly, vascular endothelial growth factor-A-induced
      chemotaxis of PTK7(+) cells was mediated by vascular endothelial growth factor
      receptor 2. In a coculture with endothelial cells, PTK7(+)CD11b(+) cells
      stabilized the vascular network for 2 weeks by expressing high levels of
      angiopoietin-1. The enhanced vascular stability was abolished by knockdown of
      angiopoietin-1 in PTK7(+)CD11b(+) cells and could be restored by angiopoietin-1
      treatment. CONCLUSIONS: We conclude that PTK7 expression in perivascular
      mononuclear cells induces vascular endothelial growth factor receptor 2 and
      angiopoietin-1 expression and thus contributes to vascular stabilization in
      angiogenesis.

PMID- 25997932
TI  - Spontaneous Aortic Regurgitation and Valvular Cardiomyopathy in Mice.
AB  - OBJECTIVE: We studied the mechanistic links between fibrocalcific changes in the
      aortic valve and aortic valve function in mice homozygous for a hypomorphic
      epidermal growth factor receptor mutation (Wave mice). We also studied myocardial
      responses to aortic valve dysfunction in Wave mice. APPROACH AND RESULTS: At 1.5
      months of age, before development of valve fibrosis and calcification, aortic
      regurgitation, but not aortic stenosis, was common in Wave mice. Aortic valve
      fibrosis, profibrotic signaling, calcification, osteogenic markers, lipid
      deposition, and apoptosis increased dramatically by 6 and 12 months of age in
      Wave mice. Aortic regurgitation remained prevalent, however, and aortic stenosis
      was rare, at all ages. Proteoglycan content was abnormally increased in aortic
      valves of Wave mice at all ages. Treatment with pioglitazone prevented abnormal
      valve calcification, but did not protect valve function. There was significant
      left ventricular volume overload, hypertrophy, and fetal gene expression, at all
      ages in Wave mice with aortic regurgitation. Left ventricular systolic function
      was normal until 6 months of age in Wave mice, but became impaired by 12 months
      of age. Myocardial transverse tubules were normal in the presence of left
      ventricular hypertrophy at 1.5 and 3 months of age, but became disrupted by 12
      months of age. CONCLUSIONS: We present the first comprehensive phenotypic and
      molecular characterization of spontaneous aortic regurgitation and volume
      overload cardiomyopathy in an experimental model. In Wave mice, fibrocalcific
      changes are not linked to valve dysfunction and are epiphenomena arising from
      structurally incompetent myxomatous valves.

PMID- 25997934
TI  - Using exome sequencing to identify the cause of myocardial hypertrophy in a
      Chinese family.
AB  - Myocardial hypertrophy is a common feature of numerous diseases. It is important
      to distinguish between these diseases in order to enable accurate diagnosis and
      the administration of appropriate therapy. Using whole-exome sequencing, the
      present study aimed to identify a pathogenic mutation in a Chinese family, which
      may lead to cardiac hypertrophy and Wolff-Parkinson-White syndrome. The proband
      from the Chinese family exhibited left ventricular hypertrophy and pre-excitation
      with a short PR interval. DNA was extracted from peripheral blood obtained from
      the subject family, and exome sequencing was performed in the proband. Polymerase
      chain reaction and direct sequencing were used to confirm the presence of a
      mutation, and confirmed that the pathogenic mutation was 5'-AMP-activated protein
      kinase subunit gamma2 (PRKAG2) (p.R302Q), which has been previously reported in a
      family with an inherited from of WPW. A stop-gain mutation in urotensin II
      receptor (UTS2R) (p.S241X), which is associated with congestive heart failure,
      was identified in the proband and in one other affected family member. It is
      important to identify the causes of myocardial hypertrophy, in order to provide a
      theoretical basis with which to improve clinical diagnosis and the assessment of
      prognosis. The results of the present study suggest that if a patient has
      myocardial hypertrophy with a short PR interval on electrocardiogram, a mutation
      in the PRKAG2 gene should be considered. In conclusion, exome sequencing methods
      may assist with the identification of causative genes in myocardial hypertrophy,
      as well as genes that are associated with an increased risk of sudden cardiac
      death.

PMID- 25997935
TI  - Fundamental Frequency Range in Japanese and English: The Case of Simultaneous
      Bilinguals.
AB  - This article reports an experiment to test whether Japanese and English speakers
      vary their fundamental frequency (f0) range as a function of the language spoken.
      Speech samples of Japanese-(American) English simultaneous bilinguals (5 males, 5
      females; all undergraduates at UC Berkeley) performing comparable reading tasks
      in their two native languages were analysed. The study builds on a relatively new
      approach to measuring f0 range that computes its high and low points from tonal
      targets in the intonational phonology. Unlike in most previous studies where f0
      range is traditionally treated as a one-dimensional measure, f0 range in this
      study is measured along two quasi-independent dimensions: level and span.
      Findings revealed statistically significant crosslanguage differences between
      Japanese and English in both dimensions. This provides new insights into the
      relation between prosodic structure and f0 range in these two typologically
      different prosodic systems.

PMID- 25997936
TI  - Getting MAD (Medical Aid in Dying) in Canada.

PMID- 25997937
TI  - Closing the Mad2 cycle.
AB  - Chromosome separation is regulated by a cycle that involves a protein undergoing
      an unusual topological conversion. 

PMID- 25997938
TI  - Comparison of Laparoscopic and Open Cystopexy in a Cadaveric Canine Model.
AB  - OBJECTIVE: To describe a technique for laparoscopic cystopexy using knotless
      barbed suture and to compare this technique with traditional cystopexy using
      standard suture in a cadaveric canine model. STUDY DESIGN: Cadaveric study.
      ANIMALS: Male canine cadavers (n = 12). METHODS: Cadavers were randomly assigned
      to 2 groups: laparoscopic (n = 6) and open (n = 6) cystopexy. Laparoscopic
      cystopexy was performed intracorporeally using barbed, glycomer 631 suture. Open
      cystopexy was performed using standard glycomer 631 suture. Pre- and
      postoperative positive contrast cystography was performed in all dogs. Cystopexy
      procedure time, length and adherence, as well as number of bladder mucosal suture
      penetrations were compared between groups. RESULTS: Mean +/- SD cystopexy
      procedure time was 14.0 +/- 3.0 minutes and 5.2 +/- 0.5 minutes for the
      laparoscopic and open groups, respectively (P = .0007). Laparoscopic and open
      cystopexy lengths were 2.5 +/- 0.4 and 2.4 +/- 0.5 cm, respectively (P = .43).
      Partial suture pullout occurred in 1 dog in the laparoscopic group but subjective
      cystopexy adherence was adequate in all dogs. Bladder mucosal suture penetration
      occurred in 3 dogs in both groups (P = .86). Two of 6 cadavers with luminal
      suture penetration had minor contrast leakage on postoperative contrast
      cystography. Pre- and postoperative contrast cystography revealed appropriate
      bladder position in all cadavers. CONCLUSION: Laparoscopic cystopexy using
      knotless suture was comparable to an open cystopexy but was associated with a
      slightly longer procedure time and should be suitable for laparoscopic cystopexy
      in vivo.

PMID- 25997939
TI  - Cutaneous lupus erythematous and hereditary angio-oedema: a familial association.

PMID- 25997940
TI  - First record of a spawning aggregation for the tropical eastern Pacific endemic
      grouper Mycteroperca olfax in the Galapagos Marine Reserve.
AB  - This study provides direct and indirect evidence of temporally and spatially
      consistent spawning aggregations for the grouper Mycteroperca olfax. Recently
      reported declines in population numbers, probably related to the direct targeting
      of aggregations by artisanal fishermen, highlight the urgent need for species
      specific management actions in the Galapagos Marine Reserve, such as minimum and
      maximum landing sizes, and the importance of protecting key aggregation sites
      with the declaration of no-take areas and the establishment of total fishing bans
      during the reproductive season. 

PMID- 25997941
TI  - QT interval, general mortality and the role of echocardiographic parameters of
      left ventricular hypertrophy: Results from the prospective, population-based
      CARLA study.
AB  - BACKGROUND: There is convincing evidence of an association between the QT
      interval on electrocardiograms and general mortality. However, results are
      inconclusive regarding the extent to which this association depends on
      ventricular mass and size. METHODS: Data were obtained from the prospective,
      population-based CARLA study, with a mean follow-up of 8.8 years, after exclusion
      of subjects with atrial fibrillation (919 men, 797 women aged 45-83 years
      remained eligible). Echocardiographic parameters were left ventricular mass
      index, left ventricular diastolic dimension index, diastolic interventricular
      septum thickness, diastolic left ventricular posterior wall and the relative left
      ventricular wall thickness. Heart rate-corrected QT interval (QTc) was measured
      with standard 12-lead electrocardiograms using the MEANS algorithm. The
      association between QTc and survival was modelled using Cox-regression models
      (crude- and covariate-adjusted). Values were standardized by dividing the QTc by
      the standard deviation. The association between QTc and survival was assessed in
      terms of tertiles of echocardiographic parameters. RESULTS: In covariate-adjusted
      models, QTc was associated with general mortality (hazard ratio (HR): 1.19; 95%
      confidence interval (CI): 1.03, 1.38). Compared with higher tertiles, subjects in
      the lowest tertile of left ventricular mass index (HR=1.73, 95% CI: 1.26, 2.36)
      showed the strongest association with general mortality, which was also true for
      the lowest tertile of diastolic left ventricular posterior wall thickness
      (HR=1.49, 95% CI: 1.10, 2.02). CONCLUSION: In the general population, the
      association between QTc and general mortality is strongest in subjects with low
      left ventricular mass index and diastolic thickness of the left ventricular
      posterior wall, thus the prognostic value of QTc needs to be interpreted with
      regard to these echocardiographic parameters.

PMID- 25997942
TI  - Effect of surfactant on regional lung function in an experimental model of
      respiratory distress syndrome in rabbit.
AB  - We assessed the changes in regional lung function following instillation of
      surfactant in a model of respiratory distress syndrome (RDS) induced by whole
      lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and
      mechanically ventilated New Zealand White rabbits. Regional specific ventilation
      (sV) was measured by K-edge subtraction synchrotron computed tomography during
      xenon washin. Lung regions were classified as poorly aerated (PA), normally
      aerated (NA), or hyperinflated (HI) based on regional density. A functional
      category was defined within each class based on sV distribution (High, Normal,
      and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance
      (H) were measured by forced oscillation technique at low frequencies before and
      after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after
      intratracheal instillation of beractant (75 mg/kg). Surfactant instillation
      improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased
      atelectasis (P < 0.001). It also significantly improved lung aeration and
      ventilation in atelectatic lung regions. However, in regions that had remained
      normally aerated after lavage, it decreased regional aeration and increased sV (P
      < 0.001) and sV heterogeneity. Although surfactant treatment improved both
      central airway and tissue mechanics and improved regional lung function of
      initially poorly aerated and atelectatic lung, it deteriorated regional lung
      function when local aeration was normal prior to administration. Local mechanical
      and functional heterogeneity can potentially contribute to the worsening of RDS
      and gas exchange. These data underscore the need for reassessing the benefits of
      routine prophylactic vs. continuous positive airway pressure and early "rescue"
      surfactant therapy in very immature infants. 

PMID- 25997943
TI  - Circulating inflammatory miRNA signature in response to different doses of
      aerobic exercise.
AB  - While moderate acute exercise has been associated with strong anti-inflammatory
      mechanisms, strenuous exercise has been linked to deleterious inflammatory
      perturbations. It is therefore fundamental to elucidate the mechanisms that
      regulate the exercise-induced inflammatory cascade. Information on novel
      regulators such as circulating inflammatory microRNAs (c-inflammamiRs) is
      incomplete. In this study, we evaluated the response of a panel of c-inflammamiRs
      to different doses of acute aerobic exercise. We first studied the exercise
      induced inflammatory cascade in serum samples of nine active middle-aged males
      immediately before and after (0 h, 24 h, 72 h) 10-km, half-marathon, and marathon
      races. Next, we analyzed the circulating profile of 106 specific c-inflammamiRs
      immediately before) and after (0 h, 24 h) 10-km (low inflammatory response) and
      marathon (high inflammatory response) races. Analysis of classical inflammatory
      parameters revealed a dose-dependent effect of aerobic exercise on systemic
      inflammation, with higher levels detected after marathon. We observed an increase
      in miR-150-5p immediately after the 10-km race. Levels of 12 c-inflammamiRs were
      increased immediately after the marathon (let-7d-3p, let-7f-2-3p, miR-125b-5p,
      miR-132-3p, miR-143-3p, miR-148a-3p, miR-223-3p, miR-223-5p, miR-29a-3p, miR-34a
      5p, miR-424-3p, and miR-424-5p). c-inflammamiRs returned to basal levels after 24
      h. Correlation and in silico analyses supported a close association between the
      observed c-inflammamiR pattern and regulation of the inflammatory process. In
      conclusion, we found that different doses of acute aerobic exercise induced a
      distinct and specific c-inflammamiR response, which may be associated with
      control of the exercise-induced inflammatory cascade. Our findings point to c
      inflammamiRs as potential biomarkers of exercise-induced inflammation, and hence,
      exercise dose. 

PMID- 25997945
TI  - Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and
      CD26 expression in rat.
AB  - The nucleoside adenosine acts on the nervous and cardiovascular systems via the
      A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma
      concentration is regulated in particular via its synthesis by CD73 and via its
      degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26
      controls the concentration of vasoactive and antioxidant peptides and hence
      regulates the oxygen supply to tissues and oxidative stress response. Although
      overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is
      well documented, the effects of hyperoxic and hyperbaric conditions on these
      elements deserve further consideration. Rats and a murine Chem-3 cell line that
      expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions;
      normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2,
      1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR
      expression, and CD26 activity were addressed in vivo, and cAMP production was
      addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine
      plasma level and T cell surface CD26 activity, whereas it increased CD73
      expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend;
      and 3) hyperbaria alone lacked significant influence on these parameters. In the
      brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric
      hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest
      effect. We found a similar pattern regarding both A2AR mRNA synthesis in the
      brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to
      downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone
      affected only A2AR expression and cAMP production. We discuss how such mechanisms
      triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen
      supply to tissues and the production of reactive oxygen species. 

PMID- 25997944
TI  - Neurogenic mechanisms underlying the rapid onset of sympathetic responses to
      intermittent hypoxia.
AB  - Sleep apnea (SA) leads to metabolic abnormalities and cardiovascular dysfunction.
      Rodent models of nocturnal intermittent hypoxia (IH) are used to mimic arterial
      hypoxemias that occur during SA. This mini-review focuses on our work examining
      central nervous system (CNS) mechanisms whereby nocturnal IH results in increased
      sympathetic nerve discharge (SND) and hypertension (HTN) that persist throughout
      the 24-h diurnal period. Within the first 1-2 days of IH, arterial pressure (AP)
      increases even during non-IH periods of the day. Exposure to IH for 7 days biases
      nucleus tractus solitarius (NTS) neurons receiving arterial chemoreceptor inputs
      toward increased discharge, providing a substrate for persistent activation of
      sympathetic outflow. IH HTN is blunted by manipulations that reduce angiotensin
      II (ANG II) signaling within the forebrain lamina terminalis suggesting that
      central ANG II supports persistent IH HTN. Inhibition of the hypothalamic
      paraventricular nucleus (PVN) reduces ongoing SND and acutely lowers AP in IH
      conditioned animals. These findings support a role for the PVN, which integrates
      information ascending from NTS and descending from the lamina terminalis, in
      sustaining IH HTN. In summary, our findings indicate that IH rapidly and
      persistently activates a central circuit that includes the NTS, forebrain lamina
      terminalis, and the PVN. Our working model holds that NTS neuromodulation
      increases transmission of arterial chemoreceptor inputs, increasing SND via
      connections with PVN and rostral ventrolateral medulla. Increased circulating ANG
      II sensed by the lamina terminalis generates yet another excitatory drive to PVN.
      Together with adaptations intrinsic to the PVN, these responses to IH support
      rapid onset neurogenic HTN. 

PMID- 25997946
TI  - Can elite athletes benefit from dietary nitrate supplementation?

PMID- 25997947
TI  - Intermittent hypoxia and neurorehabilitation.
AB  - In recent years, it has become clear that brief, repeated presentations of
      hypoxia [i.e., acute intermittent hypoxia (AIH)] can boost the efficacy of more
      traditional therapeutic strategies in certain cases of neurologic dysfunction.
      This hypothesis derives from a series of studies in animal models and human
      subjects performed over the past 35 yr. In 1980, Millhorn et al. (Millhorn DE,
      Eldridge FL, Waldrop TG. Respir Physiol 41: 87-103, 1980) showed that electrical
      stimulation of carotid chemoafferent neurons produced a persistent, serotonin
      dependent increase in phrenic motor output that outlasts the stimulus for more
      than 90 min (i.e., a "respiratory memory"). AIH elicits similar phrenic "long
      term facilitation" (LTF) by a mechanism that requires cervical spinal serotonin
      receptor activation and de novo protein synthesis. From 2003 to present, a series
      of studies demonstrated that AIH can induce neuroplasticity in the injured spinal
      cord, causing functional recovery of breathing capacity after cervical spinal
      injury. Subsequently, it was demonstrated that repeated AIH (rAIH) can induce
      recovery of limb function, and the functional benefits of rAIH are greatest when
      paired with task-specific training. Since uncontrolled and/or prolonged
      intermittent hypoxia can elicit pathophysiology, a challenge of intermittent
      hypoxia research is to ensure that therapeutic protocols are well below the
      threshold for pathogenesis. This is possible since many low dose rAIH protocols
      have induced functional benefits without evidence of pathology. We propose that
      carefully controlled rAIH is a safe and noninvasive modality that can be paired
      with other neurorehabilitative strategies including traditional activity-based
      physical therapy or cell-based therapies such as intraspinal transplantation of
      neural progenitors. 

PMID- 25997948
TI  - Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions
      in diabetic rat heart: insulin therapy or aerobic exercise?
AB  - We tested the effects of swimming training and insulin therapy, either alone or
      in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative
      stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were
      separated into control, diabetic, or diabetic plus insulin groups. Type 1
      diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups
      received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into
      sedentary or exercised rats. Trained groups were submitted to swimming (90
      min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes
      (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart
      were assessed. Diabetes reduced the amplitude and prolonged the times to peak and
      to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox
      4) expression, decreased superoxide dismutase (SOD), and increased carbonyl
      protein contents in LV tissue. In isolated mitochondria, diabetes increased
      Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening,
      uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2
      release. Swimming training corrected the time course of the [Ca(2+)]i transient,
      UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further
      normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content.
      Alongside these benefits, the combination of both therapies restored the LV
      tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In
      conclusion, the combination of swimming training with insulin replacement was
      more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress,
      and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. 

PMID- 25997949
TI  - Effect of knee angle on quadriceps strength and activation after anterior
      cruciate ligament reconstruction.
AB  - Quadriceps strength and activation deficits after anterior cruciate ligament
      (ACL) injury or surgery are typically evaluated at joint positions that are
      biomechanically advantageous to the quadriceps muscle. However, the effect of
      knee joint position and the associated changes in muscle length on strength and
      activation is currently unknown in this population. Here, we examined the effect
      of knee angle on quadriceps strength, activation, and electrically evoked torque
      in individuals with ACL reconstruction. Furthermore, we evaluated whether knee
      angle mediated the relationship between quadriceps weakness and functional
      performance after ACL reconstruction. Knee strength and activation were tested
      bilaterally at 90 degrees  and 45 degrees  of knee flexion in 11 subjects with
      ACL reconstruction using an interpolated triplet technique. The magnitude of
      electrically evoked torque at rest was used to quantify peripheral muscle
      contractile property changes, and the single-leg hop for distance test was used
      to evaluate functional performance. The results indicated that although
      quadriceps strength deficits were similar between knee angles, voluntary
      activation deficits were significantly higher in the reconstructed leg at 45
      degrees  of knee flexion. On the contrary, the side-to-side evoked torque at rest
      ratio [i.e., (reconstructed/nonreconstructed) * 100] was significantly lower at
      90 degrees  than at 45 degrees  of knee flexion. The association between
      quadriceps strength and functional performance was stronger at 45 degrees  of
      knee flexion. The results provide novel evidence that quadriceps activation is
      selectively affected at 45 degrees  of knee flexion and emphasize the importance
      of assessing quadriceps strength and activation at this position when feasible
      because it better captures activation deficits. 

PMID- 25997950
TI  - Participation in Physical Play and Leisure in Children With Motor Impairments:
      Mixed-Methods Study to Generate Evidence for Developing an Intervention.
AB  - BACKGROUND: Participation in physical play/leisure (PPP) is an important therapy
      goal of children with motor impairments. Evidence for interventions promoting PPP
      in these children is scarce. The first step is to identify modifiable, clinically
      meaningful predictors of PPP for targeting by interventions. OBJECTIVE: The study
      objective was to identify, in children with motor impairments, body function and
      structure, activity, environmental, and personal factors related to PPP and
      modifiable by therapists. DESIGN: This was a mixed-methods, intervention
      development study. The World Health Organization framework International
      Classification of Functioning, Disability and Health was used. METHODS:
      Participants were children (6-8 years old) with motor impairments, mobilizing
      independently with or without equipment and seen by physical therapists or
      occupational therapists in 6 regions in the United Kingdom, and their parents.
      Self-reported PPP was assessed with the Children's Assessment of Participation
      and Enjoyment. Modifiable-factor data were collected with therapists'
      observations, parent questionnaires, and child-friendly interviews. The
      Children's Assessment of Participation and Enjoyment, therapist, and parent data
      were analyzed using descriptive statistics and linear regression. Interview data
      were analyzed for emerging themes. RESULTS: Children's (n=195) PPP (X=18 times
      per week, interquartile range=11-25) was mainly 'recreational' (eg, pretend play,
      playing with pets) rather than 'active physical' (eg, riding a bike/scooter).
      Parents (n=152) reported positive beliefs about children's PPP but various levels
      of family PPP. Therapists reported 23 unique impairments (eg, muscle tone), 16
      activity limitations (eg, walking), and 3 personal factors (eg, child's PPP
      confidence). Children interviewed (n=17) reported a strong preference for active
      play but indicated that adults regulated their PPP. Family PPP and impairment in
      the child's movement-related body structures explained 18% of the variation in
      PPP. Family PPP explained most of the variation. LIMITATIONS: It is likely that
      the study had a degree of self-selection bias, and caution must be taken in
      generalizing the results to children whose parents have less positive views about
      PPP. CONCLUSIONS: The results converge with wider literature about the child's
      social context as a PPP intervention target. In addition, the results question
      therapists' observations in explaining PPP.

PMID- 25997952
TI  - Prevalence and genetic diversity of Rhodococcus equi in wild boars (Sus scrofa),
      roe deer (Capreolus capreolus) and red deer (Cervus elaphus) in Poland.
AB  - BACKGROUND: Rhodococcus equi is now considered an emerging zoonotic pathogen.
      Sources and routes of human infection remain unclear but foodborne transmission
      seems to be the most probable way. Strains of pig or bovine type are most often
      isolated from human cases and moreover R. equi is present in submaxillary lymph
      nodes of apparently healthy pigs and wild boars intended for human consumption.
      The aim of this study was to estimate the prevalence of R. equi in submaxillary
      lymph nodes in wild boars, roe deer and red deer. RESULTS: Samples were collected
      from 936 animals and 27 R. equi strains were isolated, from 5.1 % of wild boars
      (23/452), 0.7 % of red deer (2/272) and 0.9 % of roe deer (2/212). Genetic
      diversity of all 27 isolates was studied using VspI-PFGE method, resulting in the
      detection of 25 PFGE patterns and four PFGE clusters. PFGE patterns of the
      isolates were compared with virulence plasmid types and no concordance was
      observed. CONCLUSIONS: R. equi was present in wild animal tissues and consumption
      of the game may be a potential source of R. equi infection for humans. To the
      authors' best knowledge, this is the first epidemiological report of R. equi
      prevalence in tissues of roe deer and red deer. However, risk associated with
      wild ruminant consumption seems marginal. Investigation of R. equi transmission
      between animals and humans based exclusively on types of virulence plasmids seems
      to be insufficient to identify sources of R. equi infection for people.

PMID- 25997953
TI  - Student perceptions of gamified audience response system interactions in large
      group lectures and via lecture capture technology.
AB  - BACKGROUND: Higher education students have positive attitudes about the use of
      audience response systems (ARS), but even technology-enhanced lessons can become
      tiresome if the pedagogical approach is exactly the same with each
      implementation. Gamification is the notion that gaming mechanics can be applied
      to routine activities. In this study, TurningPoint (TP) ARS interactions were
      gamified and implemented in 22 large group medical microbiology lectures
      throughout an integrated year 1 osteopathic medical school curriculum. METHODS: A
      32-item questionnaire was used to measure students' perceptions of the gamified
      TP interactions at the end of their first year. The survey instrument generated
      both Likert scale and open-ended response data that addressed game design and
      variety, engagement and learning features, use of TP questions after class, and
      any value of lecture capture technology for reviewing these interactive
      presentations. The Chi Square Test was used to analyze grouped responses to
      Likert scale questions. Responses to open-ended prompts were categorized using
      open-coding. RESULTS: Ninety-one students out of 106 (86 %) responded to the
      survey. A significant majority of the respondents agreed or strongly agreed that
      the games were engaging, and an effective learning tool. The questionnaire
      investigated the degree to which specific features of these interactions were
      engaging (nine items) and promoted learning (seven items). The most highly ranked
      engagement aspects were peer competition and focus on the activity (tied for
      highest ranking), and the most highly ranked learning aspect was applying
      theoretical knowledge to clinical scenarios. Another notable item was the variety
      of interactions, which ranked in the top three in both the engagement and
      learning categories. Open-ended comments shed light on how students use TP
      questions for exam preparation, and revealed engaging and non-engaging attributes
      of these interactive sessions for students who review them via lecture capture.
      CONCLUSIONS: Students clearly valued the engagement and learning aspects of
      gamified TP interactions. The overwhelming majority of students surveyed in this
      study were engaged by the variety of TP games, and gained an interest in
      microbiology. The methods described in this study may be useful for other
      educators wishing to expand the utility of ARS in their classrooms.

PMID- 25997951
TI  - LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing
      bipolar cells and may play a role in cone synapse formation.
AB  - Mutations in LRIT3 lead to complete congenital stationary night blindness
      (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to
      be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3
      [no b-wave 6, (Lrit3(nob6/nob6) )], which displays similar abnormalities to
      patients with cCSNB with LRIT3 mutations. Here we compare the localization of
      components of the ON-bipolar cell signaling cascade in wild-type and
      Lrit3(nob6/nob6) retinal sections by immunofluorescence confocal microscopy. An
      anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild
      type mice revealed a specific punctate labeling in the outer plexiform layer
      (OPL), which was absent in Lrit3(nob6/nob6) mice. LRIT3 did not co-localize with
      ribeye or calbindin but co-localized with mGluR6. TRPM1 staining was severely
      decreased at the dendritic tips of all depolarizing bipolar cells in
      Lrit3(nob6/nob6) mice. mGluR6, GPR179, RGS7, RGS11 and Gbeta5 immunofluorescence
      was absent at the dendritic tips of cone ON-bipolar cells in Lrit3(nob6/nob6)
      mice, while it was present at the dendritic tips of rod bipolar cells.
      Furthermore, peanut agglutinin (PNA) labeling was severely reduced in the OPL in
      Lrit3(nob6/nob6) mice. This study confirmed the localization of LRIT3 at the
      dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the
      dependence of TRPM1 localization on the presence of LRIT3. As tested components
      of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization,
      an additional function of LRIT3 in cone synapse formation is suggested. These
      results point to a possibly different regulation of the mGluR6 signaling cascade
      between rod and cone ON-bipolar cells. 

PMID- 25997954
TI  - Hypoxia defined as a common culprit/initiation factor in mitochondrial-mediated
      proinflammatory processes.
AB  - In mammals and invertebrates, the activities of neuro- and immuno-competent
      cells, e.g., glia, which are present in nervous tissues, are deemed of critical
      importance to normative neuronal function. The responsiveness of invertebrate and
      vertebrate immuno-competent glia to a common set of signal molecules, such as
      nitric oxide and endogenous morphine, is functionally linked to physiologically
      driven innate immunological and neuronal activities. Importantly, the presence of
      a common, evolutionarily conserved, set of signal molecules in comparative animal
      groups strongly suggests an expansive intermediate metabolic profile dependent on
      high output mitochondrial ATP production and utilization. Normative bidirectional
      neural-immune communication across invertebrate and vertebrate species requires
      common anatomical and biochemical substrates and pathways involved in energy
      production and mitochondrial integrity. Within this closed-loop system, abnormal
      perturbation of the respective tissue functions will have profound ramifications
      in functionally altering associated nervous and vascular systems and it is highly
      likely that the initial trigger to the induction of a physiologically
      debilitating pro-inflammatory state is a micro-environmental hypoxic event. This
      is surmised by the need for an unwavering constant oxygen supply. In this case,
      temporal perturbations of normative oxygen tension may be tolerated for short,
      but not extended, periods and ischemic/hypoxic perturbations in oxygen delivery
      represent significant physiological challenges to overall cellular and multiple
      organ system viability. Hence, hypoxic triggering of multiple pro-inflammatory
      events, if not corrected, will promote pathophysiological amplification leading
      to a deleterious cascade of bio-senescent cellular and molecular signaling
      pathways, which converge to markedly impair mitochondrial energy utilization and
      ATP production. 

PMID- 25997956
TI  - Preoperative serum CA125 is an independent predictor for prognosis in operable
      patients with non-small cell lung cancer.
AB  - The role of serum CA125 and CEA in the prognosis of non-small cell lung cancer
      (NSCLC) remains controversial, especially in early stage patients, which need
      further clarification. Thus, in this study we carried out a large scale
      retrospective analysis of the prognostic value of CA125 and CEA in 645 patients
      with NSCLC, to explore their predictive value in the NSCLC. Patients who
      underwent curative surgical resection for NSCLC were from Zhejiang Cancer
      Hospital of China from 2006 to 2011. Microparticle enzyme immunoassay was used to
      measure preoperative serum CA125 and CEA. Univariate analyses and a multivariable
      proportional hazard Cox regression model were applied to assess the prognostic
      significance of the different covariates. Kaplan-Meier method was used to analyze
      survival curve. Both CA125 and CEA were correlated with stage, but also CA125 was
      different by grade, and CEA was related to histology. The Kaplan-Meier survival
      analysis showed that patients with elevated CA125 or CEA had unfavorable disease
      progression-free and overall survival time compared to those with normal CA125 or
      CEA. Furthermore, multivariate Cox analysis revealed that elevated CA125 had
      significantly higher risk for relapse (HR, 1.76; p=0.001) and death (HR, 1.80;
      p<0.001), but not for elevated CEA as relapse (HR, 1.06; p=0.736) and death (HR,
      1.25; p= 0.119) both were statistically non significant. This study showed that
      both CA125 and CEA play important roles in disease progression while only CA125
      as an independent predictive marker for prognosis in patients with NSCLC. 

PMID- 25997957
TI  - Receptor-interacting protein kinase 3 is a predictor of survival and plays a
      tumor suppressive role in colorectal cancer.
AB  - Receptor-interacting protein kinase 3 (RIP3) is a member of the RIP Ser/Thr
      kinase family, plays an important role in regulating cell survival, cell
      apoptosis and cell necrosis. However, the role of RIP3 in the carcinogenesis of
      colorectal cancer is still poorly understood.We used quantitative PCR and Western
      blot analysis to examine RIP3 expression in primary colorectal cancer and paired
      normal colorectal mucosa. RIP3 clinicopathological significance was assessed by
      immunohistochemical staining in 112 cases of primary colorectal cancer paired
      with noncancerous tissues. The biological function of RIP3 overexpression was
      measured by CCK8 assay and plate colony formation assay. Dual staining with
      fluorescent Annexin V and propidium iodide (PI) was used to discriminate
      apoptotic or necrotic cell death.RIP3 expression was significantly lower in
      colorectal cancer and associated with T stage, M stage and AJCC stage. Cox
      proportional hazard models showed that RIP3 expression was an independent
      prognostic factor for overall survival and disease-free survival in patients with
      colorectal cancer. Overexpression of RIP3 significantly suppressed the
      proliferation of colorectal cancer cells in vitro.Our results suggest that RIP3
      may function as a novel prognostic indicator after surgery and play a suppressive
      role in the colorectal carcinogenesis. 

PMID- 25997955
TI  - Functional bottlenecks for generation of HIV-1 intersubtype Env recombinants.
AB  - BACKGROUND: Intersubtype recombination is a powerful driving force for HIV
      evolution, impacting both HIV-1 diversity within an infected individual and
      within the global epidemic. This study examines if viral protein function/fitness
      is the major constraint shaping selection of recombination hotspots in
      replication-competent HIV-1 progeny. A better understanding of the interplay
      between viral protein structure-function and recombination may provide insights
      into both vaccine design and drug development. RESULTS: In vitro HIV-1 dual
      infections were used to recombine subtypes A and D isolates and examine
      breakpoints in the Env glycoproteins. The entire env genes of 21 A/D recombinants
      with breakpoints in gp120 were non-functional when cloned into the laboratory
      strain, NL4-3. Likewise, cloning of A/D gp120 coding regions also produced dead
      viruses with non-functional Envs. 4/9 replication-competent viruses with
      functional Env's were obtained when just the V1-V5 regions of these same A/D
      recombinants (i.e. same A/D breakpoints as above) were cloned into NL4-3.
      CONCLUSION: These findings on functional A/D Env recombinants combined with
      structural models of Env suggest a conserved interplay between the C1 domain with
      C5 domain of gp120 and extracellular domain of gp41. Models also reveal a co
      evolution within C1, C5, and ecto-gp41 domains which might explain the paucity of
      intersubtype recombination in the gp120 V1-V5 regions, despite their
      hypervariability. At least HIV-1 A/D intersubtype recombination in gp120 may
      result in a C1 from one subtype incompatible with a C5/gp41 from another subtype.

PMID- 25997958
TI  - Induction of apoptosis by capsaicin in hepatocellular cancer cell line SMMC-7721
      is mediated through ROS generation and activation of JNK and p38 MAPK pathways.
AB  - Capsaicin, one of the major pungent ingredients found in red peppers, has been
      shown to have anti-carcinogenic effect on various cancer cells through multiple
      mechanisms. In this study, we investigated the apoptotic effect of capsaicin on
      human hepatocellular cancer cell line SMMC-7721, as well as the possible
      mechanisms involved. Treatment of SMMC-7721 cells with capsaicin resulted in a
      dose-dependent inhibition of cell-viability and induction of apoptosis which was
      associated with the generation of ROS and persistent disruption of mitochondrial
      membrane potential. These effects were significantly blocked when cells were
      pretreated with a general antioxidant N-acetyl cysteine (NAC). We also found that
      capsaicin induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor
      effectively blocked capsaicin-induced SMMC-7721 cell apoptosis. In addition, NAC
      completely blocked phosphorylation of JNK and p38 MAPK induced by capsaicin. Our
      results indicate that capsaicin induced in SMMC-7721 cell apoptosis through
      generation of intracellular ROS and activation of JNK and p38 MAPK pathways. 

PMID- 25997959
TI  - Effect of TNFRSF6B neutralization antibody on cell growth suppression and
      apoptosis induction in glioma cells.
AB  - Previously, we have reported that tumor necrosis factor receptor super-family
      member 6b (TNFRSF6B) is overexpressed in glioma tissues, as well as in the
      supernatant of cultured glioma cells. However, the function of TNFRSF6B in glioma
      remains unclarified. The aim of the study was to investigate the effect of anti
      TNFRSF6B neutralization monoclonal antibody on the malignant phenotype of glioma
      cells in vitro. Three glioma cell lines U251MG, LN-308 and U87MG were treated
      with anti-TNFRSF6B antibody. Cell growth, cell cycle, apoptosis and relevant
      downstream signaling were detected further. We found that anti-TNFRSF6B antibody
      inhibited cell growth and induced apoptosis in time and dose-dependent manners in
      the glioma cells tested. Cell cycle was also arrested in G1/S-phase. Furthermore,
      anti-TNFRSF6B antibody downregulated the level of MMP-2, phospho-ERK1/2 and
      phospho-AKT. In conclusion, anti-TNFRSF6B treatment might be a critical targeted
      therapy strategy for gliomas due to its contribution to suppress cell growth and
      induce apoptosis. 

PMID- 25997960
TI  - Down-regulation of miR-205 promotes stemness of hepatocellular carcinoma cells by
      targeting PLCbeta1 and increasing CD24 expression.
AB  - Hepatocellular carcinoma (HCC) is a particularly lethal form of cancer. Overall
      survival evenafter liver surgery is unsatisfactory due to high metastatic
      capacity and recurrence rates. Cancer stem cells (CSCs) were recently proposed to
      elucidate the molecular mechanism of HCC metastasis and recurrence. In our study,
      we found that down-regulation of miR-205 promoted stem cell inhibition of
      HCC.Expression of miR-205 and PLCbeta1 was investigated by qRT-PCR. MiR-205 and
      PLCBeta1 expression were associated with disease free survival(DFS) by log-rank
      test. Computational predicting software was used to predict potential targets of
      miR-205. MiR-205 and PLCBeta1 were transfected into cells to analyze the stem
      cell inhibition. MiR-205 was significantly down-regulated and PLCbeta1
      dramatically up-regulated in tumors compared with matched tissues (P<0.0001).
      High miR-205 and low PLCbeta1 expression was found to be associated with better
      DFS. PLCbeta1 was one of the potential targets of miR-205 and the dual luciferase
      report system demonstrated that PLCbeta1 was a direct target of miR-205 in cells.
      When miR-205 and PLCbeta1 were transfected into cells, we found that the number
      of spheres increased and the CD24+ subpopulation of HCC cells dramatically
      increased.Down-regulation of miR-205 promotes stem cell inhibition of HCC by
      targeting PLCbeta1 and increasing CD24 expression. 

PMID- 25997961
TI  - miR-1271 inhibits OSCC cell growth and metastasis by targeting ALK.
AB  - Aberrant expression of miR-1271 plays prominent roles in progression of several
      cancers. However, the role of miR-1271 in oral squamous cell carcinoma (OSCC) has
      not been elucidated. The expression levels of miR-1271 and anaplastic lymphoma
      kinase (ALK) were measured by qRT-PCR in OSCC tissues and cell lines. The effects
      of miR-1271-mediated ALK on growth and metastasis of OSCC cells, transfected with
      miR-1271 with or without ALK plasmid, were assessed using MTT, colony formation,
      migration and invasion assays. Moreover, the target relationship between miR-1271
      and ALK was assessed using luciferase reporter assay, western blotting and qRT
      PCR. We found that miR-1271 was significantly decreased in OSCC tissues and cell
      lines. Overexpression of miR-1271 suppressed cell proliferation, colony
      formation, migration and invasion of OSCC cells. Furthermore, ALK was identified
      as a target of miR-1271, ALK overexpression remarkably attenuated the tumor
      suppressive effects of miR-1271 on OSCC cells. In addition, ALK was inversely
      correlated with miR-1271 expression in OSCC tissues. Taken together, our findings
      indicate that miR-1271 acts as tumor suppressor in OSCC and might be used as an
      therapeutic target for the development of treatment for OSCC. 

PMID- 25997962
TI  - Upregulation of microRNA-200a associates with tumor proliferation, CSCs phenotype
      and chemosensitivity in ovarian cancer.
AB  - Ovarian cancer is a lethal gynecologic malignancy and always has a poor
      prognosis. Despite new treatments modalities, the long term outcomes had not been
      significantly improved in the past 30 years. Although microRNA-200a (miR-200a)
      has been reported to be a prognostic marker in ovarian cancer, it's exact role in
      ovarian cancer remain unclear. In this study, we inserted the response element of
      miR-200a in ovarian cancer cell line via lentivirus-mediated transgene in vitro,
      and qRT-PCR (real time quantitative reverse transcription PCR) assay confirmed
      that miR-200a was up regulated compared with control. Then colony-formation
      assay, cell cycle analysis, CCK8 assays in vitro and xenograft experiments in
      vivo were performed and verified that miR-200a promoted proliferation, while
      blocked the formation of tumor spheroids and reduced the ratio of SP (side
      population) cells in ovarian cancer. Finally, we invalidated that miR-200a
      significantly enhanced the chemosensitivity of paclitaxel but not cisplatin in
      both adherent culture and sphere culture. Taken together, we demonstrated that
      upregulation miR-200a promoted proliferation and inhibited CSCs phenotype in
      OVCAR-3 ovarian cancer cell line, combined with cell cycle-targeting drug
      paclitaxel could effectively eliminate the "side effects" of proliferation, and
      showed evidences that this strategy may be promising for ovarian cancer
      treatment. 

PMID- 25997963
TI  - Long non-coding RNA MEG3 suppresses migration and invasion of thyroid carcinoma
      by targeting of Rac1.
AB  - Thyroid cancer, the most common primary endocrine malignancy in adult,
      imperatively requires new therapeutic studies that could target the molecular
      regulatory mechanism. Even though emerging evidence showed that long noncoding
      RNAs (Lnc-RNAs) are involved in different biological characteristic of malignant
      tumor, such as cell growth and apoptosis as well as cancer progression and
      metastasis. Limited data are available on the function of Lnc-RNAs in thyroid
      cancer invasion and metastasis. Among the 5 tested lnc-RNAs , the present study
      demonstrates that MEG3 was significantly down-regulated in papillary thyroid
      carcinoma (PTC) tissues with lymph-node metastasis than in primary thyroid
      cancer. Moreover, the down- regulated MEG3 was associated with lymph-node
      metastasis. Over-expression of MEG3 could strongly inhibit the cell migration and
      invasion in TPC-1 and HTH83 thyroid cancer cell lines. In addition, we also
      showed that Rac1 was negatively regulated by lncRNA-MEG3 at the
      posttranscriptional level, via a specific target site within the 3?UTR by dual
      luciferase reporter assay. The expression of Rac1 was inversely correlated with
      lncRNA-MEG3 expression in PTC tissues. Thus, this study suggests that MEG3 acts
      as novel suppressor of migration and invasion by targeting Rac1 gene. 

PMID- 25997964
TI  - A recombined fusion protein SP5.2/tTF induce thrombosis in tumor blood vessel.
AB  - Tumor vascular targeting is one of the most promising strategies in tumor
      therapy. Here we used E.coli to express a recombinant SP5.2/tTF fusion protein,
      which, as a tumor vascular targeting agent, consists of SP5.2 (a peptide
      selectively binding and targeting VEGFR-1 on tumor endothelial cells) and
      truncated tissue factor (tTF)and aimed to explore its anti-tumor activities.The
      SP5.2/tTF expression construct was synthesized by polymerase chain reaction (PCR)
      and recombined into plasmid pET22b(+). The fusion gene was verified by
      restriction mapping and sequencing. SP5.2/tTF was expressed in E. coli and then
      purified on a nickel-affinity chromatography column. The purified product was
      detected by SDS-PAGE. The pro-coagulant activity and binding of SP5.2/tTF to
      human umbilical vein endothelial cells (HUVECs) were monitored by FX activation
      analysis and fluorescent scanning confocal microscopy, respectively. The effect
      of SP5.2/tTF on tumor growth was analyzed in BALB/c mice bearing sarcoma 180
      (S180) tumor. The tissue localization of SP5.2/tTF and its effect on tumor vessel
      thrombosis were observed by in vivo fluorescence imaging and histological
      studies, respectively. The fusion gene was successfully cloned into pET22b(+).
      SP5.2/tTF was abundantly expressed in bacterial cells and efficiently purified by
      nickel-affinity chromatography. Functional studies showed that the protein
      retained both the coagulation activity of tTF and the binding capacity of SP5.2
      to HUVECs. In tumor xenograft studies, SP5.2/tTF selectively targeted the tumor,
      induced thrombosis, and led to retardation and even regression of tumor growth
      (growth inhibition ratio = 70%, P< 0.05). The recombinant fusion protein
      SP5.2/tTF inhibited tumor growth by selectively inducing thrombosis in tumor
      blood vessels. 

PMID- 25997965
TI  - 3D multicellular models reflect the efficiency of MSC-directed enzyme/prodrug
      treatment.
AB  - Mesenchymal stromal cells (MSC) exhibit beneficial properties to serve as
      cellular vehicles for enzyme/prodrug cancer gene therapy approaches. We have
      previously shown that engineered human adipose tissue-derived MSC in combination
      with non-toxic prodrug mediated substantial cytotoxic and antitumor effect. The
      aim of this study was to develop advanced 3D cultivation method to serve for
      modelling of the therapeutic outcome in vitro. We have used engineered MSC
      expressing fusion transgene cytosine deaminase::uracilphosphoribosyltransferase
      (CD-MSC) in combination with prodrug 5-fluorocytosine (5FC). This therapeutic
      regimen designated CD-MSC/5FC was combined with the human melanoma cells A375 or
      EGFP-A375 in both standard monolayer culture and 3-dimensional (3D) multicellular
      nodules. The extent of cytotoxicity was evaluated by standard viability assay
      MTS, ATP-based luminescence assay, fluorimetric test, measurement of Caspase-3/7
      activation and DNA laddering. The data have shown that the extent of cytotoxic
      bystander effect mediated by CD-MSC/5FC is significantly lower in 3D culture
      conditions. However, these data better recapitulate the therapeutic efficiency as
      observed previously in vivo. We suggest here to use the 3D multicellular culture
      conditions for better prediction of the therapeutic outcome in mouse xenograft
      models. 

PMID- 25997966
TI  - Expression of IAP family proteins and its clinical importance in breast cancer
      patients.
AB  - Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of
      resistance to apoptosis in various cancer cells. The aim of this study was to
      assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and
      survivin in breast cancer patients and evaluates their relationship with the
      prognostic and predictive factors and their impact to overall survival (OS) and
      progression free survival (PFS). The study was conducted with the use of tissue
      samples prospectively collected from 92 previously untreated female breast cancer
      patients. The control encompassed 10 fibroadenoma patients. The expression of
      XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry.
      XIAP expression was present in 99 % of the breast cancer patients (91/92) with
      the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer
      was significantly higher compared to the control group (p=0.006). Median
      expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range
      0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the
      rank Spearman test, strong correlations (p<0.001) were seen among the expressions
      of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation
      between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and
      survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs.
      pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months
      respectively. No significant correlations were observed among expressions of IAP
      family proteins and survival. However, low expression of XIAP in breast cancer
      showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate
      in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have
      the most significant prognostic importance. Further studies are needed to
      establish more complete prognostic and predictive values of IAP family proteins
      in breast cancer patients. 

PMID- 25997967
TI  - Impact of the 21-Gene Recurrence Score Assay in adjuvant chemotherapy selection
      for node-negative, hormone receptor-positive breast cancer in the Chinese
      population.
AB  - The 21-Gene Recurrence Score Assay has been intensively studied and recommended
      by major guidelines for treatment decision in early breast cancer. Its impact in
      adjuvant chemotherapy selection for Chinese population has not been revealed.The
      prospective part of this study enrolled consecutive node-negative, hormone
      receptor-positive patients who underwent 21-gene RS testing at Breast Surgery
      Department of PUMCH (n=134) between May 2012 and August 2013(21-gene RS group).
      Risk categories were assigned based on the RS and on standard clinicopathologic
      criteria according to St. Gallen and Adjuvant! Online. The chemotherapy selection
      and the oncologists' confidence in decision-making before and after RS testing
      were recorded. The retrospective part of this study compared the chemotherapy
      decision in the 21-gene RS group and a control group without RS testing
      (diagnosed between Jan 2011 and Apr 2012,n=170). A total of 304 patients were
      included in the analysis (134 21-gene RS group, 170 controls). Based on RS, 97
      patients were classified as low risk, 29 patients as intermediate risk, and 8
      patients as high risk. Tumor grade (P=0.002), PR expression (P<0.001) and Ki-67
      index (P<0.001) were significantly different between the 3 risk cohorts.Comparing
      the St. Gallen guidelines and RS, there was a 41% concordance between risk
      groups. By using Adjuvant! Online, the correlation between the predicted BCSM and
      RS was nominal (r=0.10). A total of 29% 21-gene RS group patients changed their
      treatment decisions after RS testing (P<0.001, 95% CI, 0.18 to 0.49) with 6%
      (8/134) patients changing to receive chemotherapy besides endocrine therapy and
      23% (31/134) changing to reject chemotherapy. After RS testing, more than one
      half of the oncologists increased their confidence level in treatment
      recommendation. In the control group, 67.6% (115/170) patients chose chemotherapy
      plus endocrine therapy. The chemotherapy percentage was much higher than that of
      21-gene RS group (30/134, 22%).This is the first study to demonstrate a reduction
      in the use of adjuvant chemotherapy in women with node-negative hormone receptor
      positive breast cancer, based on use of the RS. The RS had an impact on the
      physicians' treatment decision-making. 

PMID- 25997968
TI  - FBXO32, a new TGF-beta/Smad signaling pathway target gene, is epigenetically
      inactivated in gastric cardia adenocarcinoma.
AB  - FBXO32 has recently been identified as a TGF-beta/Smad signaling pathway target
      gene, involved in regulating cell survival and may be transcriptionally silenced
      by epigenetic mechanisms in some kind of carcinomas. The present study was to
      investigate the role and promoter methylation status of FBXO32 in gastric cardia
      adenocarcinoma (GCA), and determine the prognostic significance of FBXO32 in GCA.
      Bisulfite Conversion-Specific and Methylation-Specific PCR, real-time RT-PCR and
      immunohistochemical staining methods were used to detect the methylation status
      and expression of FBXO32 in GCA samples. The frequency of FBXO32 methylation in
      GCA tumor tissues (44.6%) was significantly higher than that in corresponding
      normal tissues (3.6%) and was associated with TNM stage, pathological
      differentiation, distant metastasis or recurrence and upper gastrointestinal
      cancers (UGIC) family history. Decreased mRNA and protein expression of FBXO32
      was observed in GCA tumor tissues and was associated with FBXO32 promoter
      methylation status. A positive correlation between FBXO32 and p-Smad2/3, Smad4
      protein expression was also found in clinical specimens. GCA patients in stage
      III and IV, with positive UGIC family history, and hypermethylation and down
      expression of FBXO32 were most likely to develop metastatic disease and also
      showed the worse survival. In all, aberrant hypermethylation of FBXO32 may be one
      of the mechanisms that lead to loss or down expression of the gene in GCA, FBXO32
      may be a functional tumor suppressor and reactivation of FBXO32 gene may has
      therapeutic potential and may be used as a prognostic marker for GCA patients. 

PMID- 25997969
TI  - Association between computed tomography-detected calcification and thyroid
      carcinoma.
AB  - This study aimed to investigate the diagnostic value of calcification detected by
      computed tomography (CT) for the differentiation of benign and malignant thyroid
      nodules. This is a retrospective study of 930 consecutive patients (709 women,
      221 men; mean age 51 years) with pathologically proven thyroid nodules. The
      characteristics of calcification on CT images were correlated with the
      pathological results. A total of 168 patients were pathologically diagnosed with
      thyroid carcinomas and 762 patients with benign thyroid nodules. Calcification
      was found in 231 cases (24.84%). The incidence of calcification was significantly
      higher in patients with thyroid carcinoma (52.38%) than in those with benign
      nodules (18.77%; P < 0.001). Detection of calcification in diagnosing thyroid
      carcinoma had a sensitivity of 52.38% (88/168) and specificity of 81.23%
      (619/762). No significant difference was noticed in the incidence of
      microcalcification (<= 2 mm) between malignant and benign nodules (P = 0.305).
      Calcification is more frequently found in thyroid carcinomas than benign nodules.
      CT detected-calcification may suggest malignant disease. Further confirmation of
      the suspected malignancy with fine-needle aspiration or surgery is still needed. 

PMID- 25997970
TI  - Prognostic value of interim and restaging PET/CT in Hodgkin lymphoma. Results of
      the CHEAP (Chemotherapy Effectiveness Assessment by PET/CT) study - long term
      observation.
AB  - Very few studies have determined the prognostic value of interim and restaging
      PET/CT in patients with Hodgkin lymphoma using current standard of care therapy
      outside clinical trials. We analyzed the effect of the results of interim and
      restaging PET/CT on the survival (overall- and relapse-free) in patients who
      received standard first-line treatment based on the stage of disease and risk
      factors. We investigated the differences between the relapse and non-relapse
      groups based on the clinical pathological characteristics of patients who had
      positive interim PET/CT results.Between January 1, 2007 and December 31, 2011,
      the staging, interim and restaging PET/CT scans of patients with Hodgkin lymphoma
      were analyzed. The Deauville criteria were used for the evaluation of interim
      PET/CT scans. One hundred and thirteen Hodgkin lymphoma patients underwent
      staging, interim and restaging PET/CT scans. None of the therapy was modified
      based on the interim PET/CT results. The median follow-up time was 43.5 months. A
      total of 62 early stage patients and 51 advanced stage patients were identified.
      The five-year overall survival rates were 93.4% in the interim PET negative group
      and 58% in the interim PET positive group (p<0.001). The five-year relapse-free
      survival rates for the negative and positive groups were 92.7% and 40.8%,
      respectively (p<0.001). The negative predictive value was 100% in the early stage
      group and 82.35% in the advanced stage group. By comparison, the positive
      predictive values were 53.8% and 58.8%, respectively, in these two groups. In the
      interim PET positive group, patients over 40 years of age had a significantly
      higher probability of relapse (p=0.057).The routine clinical use of interim
      PET/CT is highly recommended based on our investigation. However, patients with
      positive interim PET/CT results required frequent additional evaluations. 

PMID- 25997971
TI  - Biological and clinical characteristics of patients with chronic lymphocytic
      leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center.
AB  - This study aimed at mapping the frequency of IGHV3-21 and IGHV1-69 in a group of
      417 patients newly diagnosed with chronic lymphocytic leukemia (CLL) and
      described basic characteristics, cytogenetic abnormalities and prognosis of these
      patient subgroups. IGHV3-21 was found in 29 patients (7%) and IGHV1-69 in 51
      patients (12.4%). The median overall survival (OS) rates were 97 months and 85
      months in the IGHV3-21 and IGHV1-69 groups, respectively. In this small group of
      patients, the study failed to show a difference in OS of IGHV3-21 patients with
      mutated and unmutated IGHV status (p<0.597). There was also no difference in OS
      between IGHV3-21 patients with mutated IGHV status and all patients in the group
      having unmutated IGHV status (p<0.245). On the other hand, patients with IGHV3-21
      and the presence of some other adverse prognostic factors (age >= 65 years,
      lymphocyte count >= 50*109/L, serum thymidine kinase >= 9U/L, deletion of 17p)
      had statistically significantly worse OS than IGHV3-21 patients without the
      presence of these prognostic factors. The multivariate analysis of an entire
      group of Binet clinical stage A patients proved that the presence of IGHV3-21 is
      as an independent adverse prognostic factor even though there was no statistical
      difference in OS between patients with IGHV3-21 and those without IGHV3-21 in the
      entire group (p<0.769). Patients with IGHV1-69 had the same probablility of OS
      irrespective of the presence of other adverse prognostic factors; their OS was
      significantly shorter as compared with the other patients from the entire group
      (p<0.03).The study mapped the occurrence of recurrent cytogenetic changes
      detected by FISH in IGHV3-21 (subset #2 and non-subset #2) and IGHV1-69 and
      compared it with the occurrence of recurrent changes in the entire group of
      patients. In IGHV1-69 and in subset #2 IGHV3-21, higher proportions of deletion
      of 11q were found (30% and 31%, respectively), with the deletion being present in
      19.2% of the entire group of patients. None of the 3 patients with IGHV3-21 and
      deletion of 17p had subset #2. Patients with subset #2 IGHV3-21 had higher
      proportions of deletion of 13 (69%) as compared with non-subset #2 IGHV3-21
      patients (27%). 

PMID- 25997972
TI  - New perspectives in diagnosis of gynaecological cancers: Emerging role of
      circulating microRNAs as novel biomarkers.
AB  - Early diagnosis is a prerequisite of the more successful treatment of cancer. In
      gynaecological cancers, such as ovarian, endometrial and cervical cancers, the
      recent efforts are aimed at finding novel diagnostic biomarkers to help reduce
      the worldwide health burden associated with these cancers. In this review, we
      focus on the recent research progress in circulating, particularly cell-free
      microRNAs expression achieved in ovarian, endometrial and cervical cancers
      showing an opportunity to find novel diagnostic biomarkers for these malignant
      diseases. With the onset of microRNAs investigations showing their diagnostic
      potential in many diseases, their role in gynaecological cancers has been
      examined as well. However, similarly as in many other diseases, the vast majority
      of research on microRNAs expression has been dealing with tissue samples and cell
      lines. Recently, as the novel approaches focused on cell-free microRNAs
      expression have emerged, several studies identified their potential diagnostic
      and prognostic value in gynaecological cancers using blood, serum/plasma or urine
      samples. More research will be needed to establish circulating and extracellular
      microRNAs as the novel diagnostic markers for gynaecological malignancies.
      Inconsistency of results across the studies due to technical and biological
      variation, and a low number of this kind of investigations are the main potential
      pitfalls remaining to be resolved. 

PMID- 25997973
TI  - Influence of surgical resection of hepatocellular carcinoma(HCC) for hematogenous
      dissemination of HCC cells and its effect on recurrence and metastasis: 3 years
      prospective study.
AB  - Aims was to study whether hepatal surgery leads to hematogenous dissemination of
      hepatocellular carcinoma (HCC) cells and determine period of its persistence by
      nested reverse transcription-polymerase chain reaction (RT-PCR). Peripheral vein
      blood (5ml) samples were obtained from 54 HCC patients of T1N0M0 and 6 HCC
      patients of T2N0M0 stage and 20 patients with liver cavernous hemangioma(LCH)
      before operation and 48h,72h and 1 week after surgical resection of hepatoma
      between Janurary 1st, 2007 and December 31th, 2010. We detected alpha-fetoprotein
      (AFP) messenger RNA(mRNA) by nested RT-PCR perioperatively.FPmRNA of all 60 cases
      of HCC patients and 20 cases of LCH were negative before hepatal surgery, 28 of
      60 HCC cases became positve at 48h after surgery (46.7%), 16 of 60 HCC cases
      remained positive at 72h postoperatively(26.7%), none of 60 HCC patients AFPmRNA
      was detected at 1 week after hepatal surgery(0.0%). None of LCH patients were
      detected AFPmRNA after hepatal surgery(0.0%). For 28 HCC patients with AFPmRNA
      positive after hepatal surgery, 4 HCC patients developed intrahepatic tumor
      recurrences in 1st year (4/28, 14.3%),6 HCC patients relapsed in the second
      year(6/28,21.4%),10 HCC patients relapsed in the third year(10/28,35.7%). For 32
      HCC patients with AFPmRNA negative group postoperation, 5 cases relapsed in 1st
      year (5/32, 15.6%),7 cases developed intrahepatic tumor recurrences in the second
      year (7/32, 21.9%),11 cases relasped in the third year (11/32, 34.4%,P>0.05),none
      of HCC patients occured distal metastasis after surgical resection of hepatoma.
      None of LCH patients relapsed postoperation within three years.Hepatal surgery
      may cause HCC cells spreading into peripheral blood shortly, but it may be not
      concerning with recurrence or metastasis of HCC. 

PMID- 25997974
TI  - Clinicopathologic, surgical characteristics and survival outcomes of rectal
      gastrointestinal stromal tumors.
AB  - Rectal gastrointestinal stromal tumors (GISTs) are rare, and limited information
      is available concerning their management and long-term outcomes. We
      retrospectively evaluated the clinicopathological characteristics, surgical
      management, and long-term outcomes of rectal GISTs from a single institution.All
      surgically treated patients with rectal GISTS at the Department of General
      Surgery, West China Hospital, Sichuan University were identified between January
      2005 and May 2014. The overall survival (OS) and disease-free survival (DFS) were
      assessed by the Kaplan-Meier method. Forty-five patients with rectal GISTs (33
      males and 12 females) were identified. Patients presented with rectal bleeding (n
      = 13; 28.9%) and altered bowel habits (n = 11; 24.4%). The cohort study of 45
      patients included 4 very low-risk, 10 low-risk, 1 intermediate-risk, and 30 high
      risk patients. A total of 21, 13, and 11 patients underwent local resection
      (Group 1), abdominoperineal resection (Group 2), and super-low or low anterior
      resection (Group 3), respectively. Group 1 had a smaller tumor sizes and shorter
      distances from the anal verge compared with the other groups (P < 0.05). The one
      , three-, and five-year DFS rates for the entire cohort study were 90.4%, 69.3%,
      and 57.0%, respectively. High National Institutes of Health (NIH) risk categories
      (HR = 1.62) were associated with low DFS rates (P = 0.035). The DFS was
      significantly improved by imatinib mesylate (IM) adjuvant therapy in the high
      risk subgroup (P = 0.001). The type of surgery should be chosen based on the
      location and size of the rectal GISTs. Adjuvant IM therapy was associated with
      improved DFS in patients with high-risk tumors, and classification was strongly
      associated with the patient outcome. 

PMID- 25997976
TI  - Equol Inhibits LPS-Induced Oxidative Stress and Enhances the Immune Response in
      Chicken HD11 Macrophages.
AB  - BACKGROUND/AIMS: There has been increasing recent attention on the antioxidative
      capacity of equol. This study tested the effect of equol on oxidative stress
      induced by lipopolysaccharide (LPS) and regulation of immunity in chicken
      macrophages. METHODS: Chicken HD11 macrophages were challenged with LPS (100
      ng/mL) alone or with LPS (100 ng/mL) and (+/-)equol (10, 20, 40, 80, 160 MUmol/L)
      together for 24h. Evaluated responses included the contents of malondialdehyde
      (MDA) and reduced glutathione (GSH), activities of total superoxide dismutase (T
      SOD) and inducible nitric oxide synthase (iNOS), transcript abundance of
      superoxide dismutase 2 (SOD2), catalase (CAT), glutathione transferase (GST),
      Toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNFalpha) and
      interleukin-1 beta (IL-1beta), and contents of the cytokines TNFalpha, IL-1beta,
      interleukin-2 (IL-2) and interferon beta (IFNbeta). RESULTS: Exposure to LPS
      induced oxidative stress as contents of MDA increased and GSH decreased in LPS
      treated cells (P < 0.05) compared to those in control cells. Compared to LPS
      alone, co-treatment with equol (20 MUmol/L, 40 MUmol/L or 80 MUmol/L) reduced
      contents of MDA and increased those of GSH (both P < 0.05). Activity of T-SOD
      increased (P < 0.05) in cells treated with the higher contentration of equol (80
      MUmol/L or 160 MUmol/L), however, all concentrations (20 MUmol/L to 160 MUmol/L)
      increased activity of iNOS (P < 0.05). The highest concentration of equol (160
      MUmol/L) increased SOD2 and GST transcripts (P < 0.05). Equol treatment increased
      transcripts of TLR4, TNFalpha and IL-1beta (P < 0.05). And there were similar
      changes in contents of IL-1beta, IL-2, IFNbeta and TNFalpha in the cells (P <
      0.05). CONCLUSIONS: It concluded that equol can protect chicken HD11 macrophages
      from oxidative stress induced by LPS through reducing lipid peroxidation products
      and enhancing contents of antioxidants, and activities of relevant antioxidase
      enzymes; effects were also seen in gene expression related to the immune response
      and increased contents of cytokines. The optimal concentration of equol on
      antioxidation and immune enhancement in chicken macrophages was 40 MUmol/L.

PMID- 25997975
TI  - Scoping review of adherence promotion theories in pelvic floor muscle training -
      2011 ICS state-of-the-science seminar research paper i of iv.
AB  - AIMS: This paper, the first of four emanating from the International Continence
      Society's 2011 State-of-the-Science Seminar on pelvic-floor-muscle training
      (PFMT) adherence, aimed to summarize the literature on theoretical models to
      promote PFMT adherence, as identified in the research, or suggested by the
      seminar's expert panel, and recommends future directions for clinical practice
      and research. METHODS: Existing literature on theories of health behavior were
      identified through a conventional subject search of electronic databases,
      reference-list checking, and input from the expert panel. A core eligibility
      criterion was that the study included a theoretical model to underpin adherence
      strategies used in an intervention to promote PFM training/exercise. RESULTS: A
      brief critique of 12 theoretical models/theories is provided and, were
      appropriate, their use in PFMT adherence strategies identified or examples of
      possible uses in future studies outlined. CONCLUSION: A better theoretical-based
      understanding of interventions to promote PFMT adherence through changes in
      health behaviors is required. The results of this scoping review and expert
      opinions identified several promising models. Future research should explicitly
      map the theories behind interventions that are thought to improve adherence in
      various populations (e.g., perinatal women to prevent or lessen urinary
      incontinence). In addition, identified behavioral theories applied to PFMT
      require a process whereby their impact can be evaluated.

PMID- 25997977
TI  - Peripheral Neuropathies in Nonparetic Upper Extremities of Stroke Patients
      Induced by Excessive Use of a Walking Device.
AB  - BACKGROUND: Poststroke patients reportedly experience entrapment neuropathies in
      the nonparetic upper extremities, and the use of an assistive device for long
      periods may increase this risk. We examined nerve conduction velocities in
      hemiparetic patients and investigated the relationship between abnormal
      measurements and duration of walking. METHODS: Twenty-eight male hemiparetic
      outpatients who used a cane or a crutch participated in this study. Clinical
      characteristics such as age, period of time from stroke onset, side and severity
      of paresis, activities of daily living, and basic ability to walk, as well as
      each patient's approximate number of hours walking per day, were collected.
      Electrophysiological evaluation was performed via nerve conduction studies of the
      median, ulnar, and radial nerves. The clinical features were compared between
      patients with and without peripheral neuropathies. RESULTS: Twelve patients (43%)
      had peripheral neuropathies involving a total of 15 nerves. There was no
      difference in age, duration of hemiparesis, side and severity of paresis, Barthel
      index, and Functional Ambulation Classification between the 2 groups.
      Abnormalities were absent in the patients who walked at or less than an hour but
      were present in 50% and 63.4% of patients with walking times of 1-2 hours and
      more than 2 hours, respectively. CONCLUSIONS: Excessive use of a T-cane or a
      Lofstrand crutch was hypothesized to induce entrapment neuropathies in the
      nonparetic upper extremity. To prevent these injuries, a well-balanced gait
      should be established to reduce the load on the walking device.

PMID- 25997978
TI  - Self-Care Self-Efficacy Correlates with Independence in Basic Activities of Daily
      Living in Individuals with Chronic Stroke.
AB  - BACKGROUND: (1) To characterize the self-care self-efficacy (SCSE) of community
      dwelling individuals with chronic stroke and (2) to determine the contribution of
      SCSE to the independence in basic and instrumental activities of daily living
      (BADL and IADL) and the participation of individuals with chronic stroke. SCSE is
      the confidence in one's own ability to perform self-care activities. METHODS:
      This cross-sectional study included fifty community-dwelling individuals mean
      (SD) age 59.8 (9.3) years, mean (SD) 3.1 (1.7) years post-stroke who were able to
      walk at least 10 meters. SCSE was assessed using the Stroke Self-Efficacy
      Questionnaire (SSEQ), BADL was assessed by the Functional Independence Measure
      (FIM) (interview), the IADL questionnaire assessed IADL and the Physical Activity
      Scale for Individuals with Physical Disabilities (PASIPD) assessed participation.
      Correlation and regression analyses were performed after controlling for grip
      strength, executive functions and gait speed, factors known to influence
      independence in daily living. RESULTS: The mean SCSE level was moderate-high
      (70%). Significant moderate correlations were found between SCSE to independence
      in BADL (r = .596, P < .001), IADL (r = .567, P < .001) and participation (r =
      .340, P < .005). SCSE of our cohort explained 7.4% of the variance of the
      individual's independence in BADL after controlling for executive functions and
      gait speed, but did not contribute to their independence in IADL and
      participation. CONCLUSIONS: Higher SCSE of individuals with chronic stroke
      contributes to more independence in BADL. Additional questionnaires regarding
      self efficacy for IADL should be developed and investigated.

PMID- 25997979
TI  - Prevalence and Profile of Poststroke Subjective Cognitive Complaints.
AB  - BACKGROUND: Subjective cognitive complaints (SCCs) are common after stroke, but
      detailed information about how SCCs differ between patients with stroke versus
      stroke-free individuals is not available. We evaluated the prevalence and profile
      of the 2 SCC components (content and worry) in patients 3 months after stroke
      versus controls using both a generic and a stroke-specific instrument. METHODS:
      Using a cross-sectional design, 142 patients were compared to 135 controls
      (matched at group level on age, sex, and estimate of premorbid intelligence
      quotient). SCC-content and SCC-worry were assessed using the Cognitive Failures
      Questionnaire (CFQ) and the Checklist of Cognitive and Emotional Consequences
      after stroke (CLCE-24). Univariate and multivariate linear (for continuous
      scores) and logistic (for dichotomous scores) regression analyses were used to
      explore differences between patients and controls on both instruments. RESULTS:
      Based on the CLCE, patients reported more SCC-content (standardized beta = .21,
      p.001) and SCC-worry (standardized beta = .18, p.02) than controls in
      multivariate analyses. Profiles indicated that stroke was associated in
      particular with SCC-content on the domains of memory, attention, executive
      functioning, expressive language, and with attention-related SCC-worry. In
      contrast, no group differences were found on SCC-content and SCC-worry assessed
      by the CFQ. CONCLUSIONS: The prevalence and profile of SCC-content and SCC-worry
      differ between patients and controls 3 months after stroke. The instrument used
      may, however, determine prevalence estimates. Stroke-specific inventories that
      differentiate between SCC-content and SCC-worry are preferable when attempting to
      determine SCC after stroke.

PMID- 25997980
TI  - Magnetic Resonance Imaging in Acute Ischemic Stroke Patients with Mild Symptoms:
      An Opportunity to Standardize Intravenous Thrombolysis.
AB  - BACKGROUND: Patients presenting with mild stroke symptoms are excluded
      inconsistently from intravenous (IV) thrombolysis. We aimed to compare acute
      magnetic resonance imaging findings in patients with mild symptoms to those with
      more severe deficits to identify clinically mild patients who might benefit from
      IV thrombolysis. METHODS: We retrospectively studied consecutive stroke patients
      presenting with perfusion deficit who underwent time-of-flight magnetic resonance
      angiography within 24 hours of time last seen normal. Two raters measured the
      lesion volumes on diffusion-weighted imaging (DWI) and perfusion-weighted imaging
      (PWI) with mismatch (MM) calculated as PWI minus DWI. Occlusion site was
      categorized as "proximal," "distal," or "magnetic resonance angiography-negative"
      by consensus review. Stroke with mild symptoms was defined as admit National
      Institutes of Health Stroke Scale score of 4 or less. Values were reported as n
      (%). RESULTS: Ninety-one patients were included; 56 (61.5%) with nonmild and 35
      (38.5%) with mild symptoms. After stratifying for occlusion site, there were no
      differences in PWI and MM lesion volumes for the nonmild versus mild patients (P
      = .34-.98 and P = .54-1, respectively). Furthermore, there was a trend for
      thrombolyzed mild stroke patients (88%, n = 7 of 8) to more likely have a
      favorable clinical outcome (discharge modified Rankin score <= 2) versus
      untreated patients (70%, n = 16 of 23). CONCLUSIONS: When present, conspicuous
      vessel occlusions in clinically mild stroke patients are concomitant with similar
      perfusion deficit and MM volumes in more clinically severe stroke patients.
      Coupled with a trend toward better outcomes in mild stroke patients who were
      treated with IV tissue plasminogen activator (t-PA), this could indicate that
      advanced imaging may be used in standardizing the way these patients are selected
      for IV t-PA therapy.

PMID- 25997982
TI  - Prevalence of antibiotic-resistant bacteria in a lake for the storage of
      reclaimed water before and after usage as cooling water.
AB  - Wastewater reclamation and reuse is a promising way to relieve water scarcity by
      substituting for natural water consumption by industrial cooling. However, health
      concerns regarding cooling water originating from reclaimed water are increasing
      because an abundance of antibiotic-resistant bacteria (ARB) has been detected in
      reclaimed water. To assess the potential increase of ARB risks in reclaimed water
      after reuse for industrial cooling, the prevalence of six types of ARB was
      investigated in water and sediment samples from Lake Gaobeidian, which serves as
      an artificial circular storage reservoir for reclaimed water for cooling reuse.
      The effect of treated wastewater and cooling water drainage on the ARB
      distribution in water and sediment samples was also studied. The results showed
      that the concentration levels of six types of ARB in lake water samples were as
      high as those in treated wastewater. The annual median concentrations of total
      heterotrophic bacteria (HPC) and ARB in discharged cooling water after usage were
      0.6-log and 0.4-log higher than those in treated wastewater and the cooling water
      intake site, respectively, indicating that the process of cooling water usage
      enhanced the proliferation of HPC and consequently increased the concentrations
      of ARB. Furthermore, the percentages of penicillin-, ampicillin-, and cephalothin
      resistant bacteria in water were 30-57%, 36-48%, and 23-40% higher than those in
      sediment, respectively. However, the proportions of chloramphenicol-resistant
      bacteria in water were 35-85% lower than those in sediment. Quantitative
      evaluation of antibiotic resistance showed that HPC in water had a significant
      tolerance to penicillin and chloramphenicol, with 50% inhibitory concentrations
      reaching 22.90 mg L(-1) and 29.11 mg L(-1), respectively. 

PMID- 25997981
TI  - Elevated levels of GABA+ in migraine detected using (1) H-MRS.
AB  - gamma-Aminobutyric acid (GABA) has been implicated in several pain conditions,
      yet no study has systematically evaluated GABA levels in migraine using (1) H
      MRS. The accurate detection, separation and quantification of GABA in individuals
      with migraine could elucidate the role of this neurotransmitter in migraine
      pathophysiology. Such information may eventually be useful in the diagnosis and
      development of more effective treatments for migraine. The aims of this study
      were therefore to compare the concentration of GABA+ in individuals with migraine
      with that in asymptomatic individuals, and to determine the diagnostic potential
      of GABA+ in the classification of those with or without migraine. In this case
      control study, GABA+ levels in the brain were determined in 19 participants with
      migraine and 19 matched controls by (1) H-MRS using Mescher-Garwood point
      resolved spectroscopy (MEGA-PRESS) sequence. The diagnostic accuracy of GABA+ for
      the detection of migraine and the optimal cut-off value were determined by
      receiver operating characteristic analysis. GABA+ levels were significantly
      higher (p = 0.002) in those with migraine [median, 1.41 institutional units (IU);
      interquartile range, 1.31-1.50 IU] than in controls (median, 1.18 IU;
      interquartile range, 1.12-1.35 IU). The GABA+ concentration appears to have good
      accuracy for the classification of individuals with or without migraine [area
      under the curve (95% confidence interval), 0.837 (0.71-0.96); p < 0.001]. The
      optimal GABA+ cut-off value for migraine was 1.30 IU, with a sensitivity of
      84.2%, specificity of 68.4% and positive likelihood ratio of +2.67. The outcomes
      of this study suggest altered GABA metabolism in migraine. These results add to
      the scarce evidence on the putative role of GABA in migraine and provide a basis
      to further explore the causal relationship between GABA+ and the pathophysiology
      of migraine. This study also demonstrates that GABA+ concentration has good
      diagnostic accuracy for migraine. These findings offer new research and practice
      directions for migraine diagnosis.

PMID- 25997983
TI  - The Relationship between Positive Peritoneal Cytology and the Prognosis of
      Patients with Uterine Cervical Cancer.
AB  - OBJECTIVE: We investigated the association of positive peritoneal cytology with
      prognosis in uterine cervical cancer. STUDY DESIGN: We reviewed the medical
      records and cytologic materials of 225 Japanese patients with FIGO IB1-IVB
      uterine cervical cancer who had undergone surgery at our University Hospital
      between 1993 and 2012. Univariate and multivariate regression analyses were
      performed for statistical analysis. RESULTS: Positive peritoneal cytology was
      noted in 6 of 225 patients (2.7%). Positive peritoneal cytology was found in 4 of
      149 patients (2.6%) with squamous cell carcinoma (SCC) and in 2 of 70 patients
      (2.8%) with non-SCC (p = 0.9434). The 5-year survival rate of patients with
      positive peritoneal cytology was significantly lower than that of patients with
      negative cytology (50 vs. 84.6%, p = 0.001) in univariate survival analysis.
      However, peritoneal cytology no longer remained significant in multivariate
      analysis. CONCLUSION: Although we conclude that positive peritoneal cytology in
      uterine cervical cancer is a poor prognostic factor, further investigation and
      multi-institutional studies are necessary.

PMID- 25997984
TI  - Central and peripheral pulmonary vascular resistance: Implications for who should
      undergo pulmonary thromboendarterectomy.
AB  - Pulmonary thromboendarterectomy remains a technically challenging procedure with
      variable outcomes with regard to improvement in pulmonary function. Reducing the
      resistance to flow between the pulmonary valve and the pulmonary capillary bed is
      the key aim of surgery. The resistance to flow is due to the combination of
      resistance due to the central clot and distal capillary resistance. We
      hypothesise that the use of fluid mechanics in combination with modern radiology
      and electronic circuit theory can potentially predict who should or should not
      undergo a thromboendarterectomy. Electronic circuit theory of two resistors in
      series was utilised to demonstrate the concept of a model of a central clot and
      the peripheral pulmonary capillary bed. A simplified 2D model of the lungs
      utilising finite element analysis and Poiseuille's law was constructed for proof
      of principle. Modelling predicts that cardiac output and anatomical obstruction
      interplay and can have profound effects on the outcomes after
      thromboendarterectomy. Identical pulmonary artery pressures, due to differing
      cardiac outputs and identical anatomical obstructions due to thrombus can have
      very different physiological outcomes with regard to changes in pulmonary artery
      pressure. Modelling the pulmonary vasculature to determine central and peripheral
      pulmonary vascular resistance may help in predicting who should undergo pulmonary
      thromboendarterectomy. Mathematical modelling can potentially predict which
      patients have haemodynamically significant clots in their pulmonary arteries that
      thromboendarterectomy may potentially help in the setting of pulmonary capillary
      disease. 

PMID- 25997985
TI  - Extract of fetal membrane would inhibit thrombosis and hemolysis.
AB  - The innermost layer of fetal membranes is amnion which has anti-adhesive, anti
      inflammation and viscoelastic properties, as well as low immunogenicity. Amniotic
      membrane has been employed in variety of clinical fields as a natural
      biomaterial. Amniotic epithelial cells possess stem cell characteristics and
      capability to differentiate into endothelial cells. The basement membrane of
      amnion is an extracellular matrix enriched scaffold to support adhesion of
      endothelial cells. The matrix of amniotic membrane contains two kinds of
      glycosaminoglycans including perlecan (a heparan sulfate proteoglycan) and
      hyaluronic acid which both inhibit blood coagulation. Moreover, the other
      ingredients of amniotic membrane such as pigment-epithelium derived factor
      (PEDF), IL-10, MMP-9 inhibit platelet aggregation. Based on some biochemical and
      biomechanical evidences, we hypothesized in this paper that amniotic membrane
      could prevent thrombosis and hemolysis; therefore, has the capability to be
      applied in blood contacting devices and implants. 

PMID- 25997986
TI  - iGWAS: Integrative Genome-Wide Association Studies of Genetic and Genomic Data
      for Disease Susceptibility Using Mediation Analysis.
AB  - Genome-wide association studies (GWAS) have been a standard practice in
      identifying single nucleotide polymorphisms (SNPs) for disease susceptibility. We
      propose a new approach, termed integrative GWAS (iGWAS) that exploits the
      information of gene expressions to investigate the mechanisms of the association
      of SNPs with a disease phenotype, and to incorporate the family-based design for
      genetic association studies. Specifically, the relations among SNPs, gene
      expression, and disease are modeled within the mediation analysis framework,
      which allows us to disentangle the genetic effect on a disease phenotype into two
      parts: an effect mediated through a gene expression (mediation effect, ME) and an
      effect through other biological mechanisms or environment-mediated mechanisms
      (alternative effect, AE). We develop omnibus tests for the ME and AE that are
      robust to underlying true disease models. Numerical studies show that the iGWAS
      approach is able to facilitate discovering genetic association mechanisms, and
      outperforms the SNP-only method for testing genetic associations. We conduct a
      family-based iGWAS of childhood asthma that integrates genetic and genomic data.
      The iGWAS approach identifies six novel susceptibility genes (MANEA, MRPL53,
      LYCAT, ST8SIA4, NDFIP1, and PTCH1) using the omnibus test with false discovery
      rate less than 1%, whereas no gene using SNP-only analyses survives with the same
      cut-off. The iGWAS analyses further characterize that genetic effects of these
      genes are mostly mediated through their gene expressions. In summary, the iGWAS
      approach provides a new analytic framework to investigate the mechanism of
      genetic etiology, and identifies novel susceptibility genes of childhood asthma
      that were biologically meaningful. 

PMID- 25997987
TI  - Disturbed body perception, reduced sleep, and kinesiophobia in subjects with
      pregnancy-related persistent lumbopelvic pain and moderate levels of disability:
      An exploratory study.
AB  - BACKGROUND: For a small but significant group, pregnancy-related lumbopelvic pain
      may become persistent. While multiple factors may contribute to disability in
      this group, previous studies have not investigated sleep impairments, body
      perception or mindfulness as potential factors associated with disability post
      partum. OBJECTIVES: To compare women experiencing no pain post-pregnancy with
      those experiencing pregnancy-related persistent lumbopelvic pain (either low- or
      high-level disability) across multiple biopsychosocial domains. DESIGN: Cross
      sectional. METHODS: Participants completed questionnaires for thorough profiling
      of factors thought to be important in pregnancy-related lumbopelvic pain.
      Specific measures were the Urinary Distress Inventory, Medical Outcomes Study
      Sleep Scale, Back Beliefs Questionnaire, Tampa Scale for Kinesiophobia,
      Depression Anxiety Stress Scale, Coping Strategies Questionnaire, Pain
      Catastrophising Scale, The Fremantle Back Awareness Questionnaire and the Mindful
      Attention Awareness Scale. Women where categorised into three groups; pain free
      (n = 26), mild disability (n = 12) and moderate disability (n = 12) (based on
      Oswestry Disability Index scores). Non-parametric group comparisons were used to
      compare groups across the profiling variables. RESULTS: Differences were
      identified for kinesiophobia (p = 0.03), body perception (p = 0.02), sleep
      quantity (p < 0.01) and sleep adequacy (p = 0.02). Generally subjects in the
      moderate disability group had more negative findings for these variables.
      CONCLUSION: Disturbances in body-perception, sleep and elevated kinesiophobia
      were found in pregnancy-related lumbopelvic pain subjects with moderate
      disability, factors previously linked to persistent low back pain. The cross
      sectional nature of this study does not allow for identification of directional
      pathways between factors. The results support the consideration of these factors
      in the assessment and management of pregnancy-related lumbopelvic pain.

PMID- 25997988
TI  - Diagnostic application of KRAS mutation testing in uterine microglandular
      proliferations.
AB  - Microglandular proliferations often pose a diagnostic challenge in small
      endocervical and endometrial biopsies. Microglandular hyperplasia (MGH) is one of
      the most common pseudoneoplastic glandular proliferations of uterine cervix,
      which can closely mimic endometrial adenocarcinomas (EAC) with a microglandular
      pattern (microglandular EAC). Although MGH is typically characterized by
      relatively uniform nuclei and rare to absent mitoses, atypical forms with
      architectural and/or cytologic deviation from the usual morphology have been
      previously described. Recently, a series of MGH with high mitotic activity has
      also been documented. Although careful morphological assessment and
      immunohistochemical workup can resolve the diagnostic dilemma in some cases,
      additional differential diagnostic tools are needed to separate both the common
      and atypical variants of MGH from EAC with microglandular pattern. Frequent KRAS
      mutation has been previously reported in endometrial complex mucinous lesions and
      endometrial mucinous carcinomas. However, the diagnostic utility of KRAS mutation
      analysis has not yet been explored in the context of cervical and endometrial
      microglandular lesions. Twelve mitotically active MGH cases and 15 cases of EAC
      with microglandular growth pattern were selected for the study. KRAS mutation
      analysis was performed in all cases by highly sensitive single-strand
      conformation polymorphism analysis. Clinical history and follow-up data were
      retrieved from electronic medical records. KRAS mutation was absent in all MGH
      cases, whereas 9 (60%) of 15 microglandular EAC cases tested positive for KRAS
      mutation. Our data indicate that KRAS mutation analysis may offer additional
      discriminatory power in separating benign MGH from EAC with microglandular
      pattern. 

PMID- 25997989
TI  - Cross-current leaching of indium from end-of-life LCD panels.
AB  - Indium is a critical element mainly produced as a by-product of zinc mining, and
      it is largely used in the production process of liquid crystal display (LCD)
      panels. End-of-life LCDs represent a possible source of indium in the field of
      urban mining. In the present paper, we apply, for the first time, cross-current
      leaching to mobilize indium from end-of-life LCD panels. We carried out a series
      of treatments to leach indium. The best leaching conditions for indium were 2M
      sulfuric acid at 80 degrees C for 10min, which allowed us to completely mobilize
      indium. Taking into account the low content of indium in end-of-life LCDs, of
      about 100ppm, a single step of leaching is not cost-effective. We tested 6 steps
      of cross-current leaching: in the first step indium leaching was complete,
      whereas in the second step it was in the range of 85-90%, and with 6 steps it was
      about 50-55%. Indium concentration in the leachate was about 35mg/L after the
      first step of leaching, almost 2-fold at the second step and about 3-fold at the
      fifth step. Then, we hypothesized to scale up the process of cross-current
      leaching up to 10 steps, followed by cementation with zinc to recover indium. In
      this simulation, the process of indium recovery was advantageous from an economic
      and environmental point of view. Indeed, cross-current leaching allowed to
      concentrate indium, save reagents, and reduce the emission of CO2 (with 10 steps
      we assessed that the emission of about 90kg CO2-Eq. could be avoided) thanks to
      the recovery of indium. This new strategy represents a useful approach for
      secondary production of indium from waste LCD panels. 

PMID- 25997990
TI  - Characterization of odor emission on the working face of landfill and
      establishing of odorous compounds index.
AB  - Temporal variation (seasonal and daily) of odor emission on the working face of a
      large sanitary landfill in China was characterized through a 2 yearlong case
      study. Odor pollution was most serious in spring and autumn, while lower odor
      concentrations were detected in summer and winter. The daily fluctuation of odor
      concentration on the working face showed that 2:00am, 6:00am, 2:00pm and 10:00pm
      were the "most probable times" for odor pollution occurrence, which deserves
      focused attention in odor control projects. Correlations analysis found that 41%
      of the variance in odor concentrations can be explained by the chemical
      concentrations of odorous compounds. Moreover, the selection criteria for the
      index of odorous compounds were also established by evaluating the odor
      concentration, contribution to odor strength and the frequency of each compound
      present in all the samples. Ethyl alcohol, alpha-piene, hydrogen sulfide,
      dimethyl sulfide, limonene, methyl mercaptan, dimethyl disulfide, and diethyl
      sulfide comprise the index of odorous compounds on the working face of typical
      municipal solid waste landfill in China. 

PMID- 25997991
TI  - Improving health-related quality of life in single-sided deafness: a systematic
      review and meta-analysis.
AB  - Unilateral severe-to-profound hearing loss, or single-sided deafness (SSD),
      impairs listening abilities supported by the use of two ears, including speech
      perception in background noise and sound localisation. Hearing-assistive devices
      can aid listening by re-routing sounds from the impaired to the non-impaired ear
      or by restoring input to the impaired ear. A systematic review of the literature
      examined the impact of hearing-assistive devices on the health-related quality of
      life (HRQoL) of adults with SSD as measured using generic and disease-specific
      instruments. A majority of studies used observational designs, and the quality of
      the evidence was low to moderate. Only two studies used generic instruments. A
      mixed-effect meta-analysis of disease-specific measures suggested that hearing
      assistive devices have a small-to-medium impact on HRQoL. The Speech, Spatial and
      Qualities of Hearing Scale and the Health Utilities Index Mark 3 (HUI3) were
      identified as instruments that are sensitive to device-related changes in disease
      specific and generic HRQoL, respectively.

PMID- 25997993
TI  - Angiogenic Factors in Cord Blood of Preterm Infants Predicts Subsequently
      Developing Bronchopulmonary Dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) of prematurity is associated with
      impaired angiogenesis. Excess soluble fms-like tyrosine kinase-1 (sFlt-1) and
      lower levels of vascular endothelial growth factor (VEGF) impaired
      alveolarization in preterm rats. Overexpression of placenta growth factor (PlGF)
      in mice caused airspace enlargement, which is similar to BPD pathologically. Our
      study aimed to clarify whether cord blood levels of these angiogenic factors were
      associated with the development of BPD in preterm infants. METHODS: Preterm
      infants of gestational age (GA) <35 weeks who already had all the data of cord
      blood VEGF, PlGF, and sFlt-1 levels in our previous studies were enrolled. Cord
      blood levels of VEGF, PlGF, and sFlt-1 were collected. BPD was defined as the
      need for supplemental oxygen or mechanical ventilation support at the
      postmenstrual age of 36 weeks. We used the Mann-Whitney U test for comparison
      between infants with and without BPD, and multivariate analysis with logistic
      regression to assess the association of these molecules and the development of
      BPD. RESULTS: Infants with BPD had lower GA [(27 weeks (24-34) vs. 31 weeks (28
      24)], lower birth body weight [882 g (620-1232) vs. 1538 g (886-2328)], a higher
      incidence of respiratory distress syndrome (RDS) (58% vs. 14%), and a higher
      level of PlGF [21.45 pg/dL (6.03-474.01) vs. 7.43 pg/dL (0.09-23.75)] as compared
      with those infants without BPD. The levels of VEGF and sFlt-1 did not differ
      significantly between the two groups. Multivariate logistic regression revealed
      that lower birth body weight (p = 0.022) and higher level of PlGF (p = 0.012)
      were significantly correlated with the development of BPD independently. There
      was no significant association between the level of VEGF or sFlt-1 and the
      development of BPD. CONCLUSION: Cord blood level of PlGF, rather than VEGF or
      sFlt-1, was significantly increased in the BPD group. Consistent with our
      previous report, cord blood level of PlGF may be considered as a biomarker to
      predict subsequently developing BPD in preterm infants.

PMID- 25997992
TI  - Emerging complexity and new roles for the RIG-I-like receptors in innate
      antiviral immunity.
AB  - Innate immunity is critical for the control of virus infection and operates to
      restrict viral susceptibility and direct antiviral immunity for protection from
      acute or chronic viral-associated diseases including cancer. RIG-I like receptors
      (RLRs) are cytosolic RNA helicases that function as pathogen recognition
      receptors to detect RNA pathogen associated molecular patterns (PAMPs) of virus
      infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and
      bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger
      downstream signaling cascades that induce innate immunity that controls viral
      replication and spread. Products of RLR signaling also serve to modulate the
      adaptive immune response to infection. Recent studies have additionally connected
      RLRs to signaling cascades that impart inflammatory and apoptotic responses to
      virus infection. Viral evasion of RLR signaling supports viral outgrowth and
      pathogenesis, including the onset of viral-associated cancer. 

PMID- 25997994
TI  - Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic
      Review.
AB  - Relapses (episodic exacerbations of neurological signs or symptoms) are a
      defining feature of relapsing-remitting multiple sclerosis (MS), the most
      prevalent MS phenotype. While their diagnostic value relates predominantly to the
      definition of clinically definite MS, their prognostic value is determined by
      their relatively high associated risk of incomplete remission resulting in
      residual disability. The mechanisms governing a relapse incidence are unknown,
      but numerous modifiers of relapse risk have been described, including demographic
      and clinical characteristics, many of which represent opportunities for improved
      disease management. Also relapse phenotypes have been associated with patient and
      disease characteristics and an individual predisposition to certain phenotypic
      presentations may imply individual neuroanatomical disease patterns. While
      immunomodulatory therapies and corticosteroids represent the mainstay of relapse
      prevention and acute management, respectively, their effect has only been partial
      and further search for more efficient relapse therapies is warranted. Other areas
      of research include pathophysiology and determinants of relapse incidence,
      recurrence and phenotypes, including the characteristics of the relapsing and non
      relapsing multiple sclerosis variants and their responsiveness to therapies.

PMID- 25997995
TI  - miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in
      HCC chemotherapy.
AB  - Mounting evidence suggests that microRNAs (miRNAs) play important roles in the
      development of cancer by targeting expression of tumor-related genes. In the
      present study, downregulation of miR-193b was observed in hepatocellular
      carcinoma (HCC) tissues and HCC cell lines by quantitative RT-PCR analyses,
      suggesting that miR-193b is a tumor-suppressor in HCC. More importantly, miR-193b
      significantly enhanced the cytotoxicity of cisplatin in HepG2 cells by targeting
      Mcl-1. Knockdown of the Mcl-1 gene by specific siRNA exhibited a function similar
      to miR-193b on sensitizing HepG2 cells to cisplatin-inducing cytotoxicity.
      Furthermore, the miR-193b-induced sensitization of HepG2 cells to cisplatin
      cytotoxicity was abolished by the transfection of Mcl-1 expression plasmid that
      lacked the 3'-untranslated region (3'-UTR). In addition, activation of caspase-3
      was needed for sensitization by miR-193b to cisplatin-mediated cell death. Thus,
      the present study revealed the downregulation of miR-193b in HCC cells and
      illustrated a synergistic effect on cisplatin-induced apoptosis by targeting Mcl
      1. 

PMID- 25997996
TI  - Overlap of gastroesophageal reflux disease and functional bowel disorders in the
      general Chinese rural population.
AB  - OBJECTIVE: This study aimed to investigate the prevalence of the overlap between
      gastroesophageal reflux disease (GERD) and functional bowel disorders (FBD) in
      the general population in rural areas in China. METHODS: A population-based cross
      sectional study was conducted in six villages in Nanmazhuang area in Lankao
      County (Henan Province, China) from December 2010 to October 2011. The GERD
      questionnaire (GerdQ) and Rome III criteria were used for the diagnosis of GERD
      and FBD and to determine the prevalence of GERD-FBD overlap. RESULTS: The
      response rate to the questionnaires of the patients was 91.5%. In all, 2950 of
      3700 residents with a mean age of 42.4 +/- 16.8 years were included. Among them,
      4.8% were diagnosed with GERD and 4.6% with FBD. The proportion of respondents
      with FBD was significantly higher in the GERD group than that in the non-GERD
      group (25.53% vs 3.60%, P < 0.05). The prevalence of GERD in the FBD group was
      significantly higher than that in the non-FBD group (26.28% vs 3.73%, P < 0.05).
      The prevalence of GERD-FBD overlap in the general rural population was 1.22%.
      Logistic regression analysis indicated that anxiety was an independent predictor
      for the GERD-FBD overlap in GERD and FBD (odds ratio [OR] 1.05, 95% confidence
      interval [CI] 1.02-1.09 and OR 1.06, 95% CI 1.02-1.10, respectively). CONCLUSION:
      GERD-FBD overlap is more common than expected by chance in the general rural
      population, and anxiety is significantly related to the overlap.

PMID- 25997997
TI  - Validating the anticancer potential of carbon nanotube-based therapeutics through
      cell line testing.
AB  - Recent years have witnessed the booming development of carbon nanotubes (CNTs)
      and their composites in biological and medicine. By virtue of their unique
      physicochemical properties, CNTs have emerged as potential tools in biomedical
      applications as a result of their development as safe, effective nanomedicines.
      Diverse cell lines have been shown to be best-fit experimental models for
      evaluating the pharmacokinetic parameters, cell viability, and cytotoxicity of
      CNTS, as well as their drug efficacy ex vivo, which can then be correlated with
      their in vivo performance. The biological activities and cytotoxic effects of
      CNTs are dependent on their surface chemistry, and how they are purified and
      functionalized. Here, we focus on aspects of CNTs including their
      functionalization, and their biomedical potential and limitations, emphasizing
      the toxicological aspects of functionalized CNTs using various cell lines. The
      outlook for CNT-based nanomedicine, particularly in cancer treatment, is
      fascinating and encouraging. In vitro cell line data can assist the selection of
      specific cancer cell lines for the evaluation of anticancer bioactive-loaded CNTs
      as a novel drug delivery tool in the diagnosis and treatment of cancer. 

PMID- 25997999
TI  - The effect of transcranial Direct Current Stimulation on gamma activity and
      working memory in schizophrenia.
AB  - Working memory impairments in schizophrenia have been strongly associated with
      abnormalities in gamma oscillations within the dorsolateral prefrontal cortex
      (DLFPC). We recently published the first ever study showing that anodal
      transcranial Direct Current Stimulation (tDCS) to the left DLPFC was able to
      significantly improve working memory performance in schizophrenia. In the current
      paper we present a secondary analysis from this study, specifically looking at
      the effect of tDCS on gamma activity and its relationship to working memory. In a
      repeated measures design we assessed the impact of anodal tDCS (1mA, 2mA, sham)
      on gamma activity in the left DLPFC at three time-points post-stimulation (0min,
      20min, 40min). EEG data was available for 16 participants in the 2mA condition,
      13 in the 1mA condition and 12 in the sham condition. Following 2mA stimulation
      we found a significant increase in gamma event-related synchronisation in the
      left DLPFC, this was in the context of a significantly improved working memory
      performance. There was also a significant decrease in gamma event-related
      synchronisation, with no changes in working memory, following sham stimulation.
      The current study provides preliminary evidence that tDCS may enhance working
      memory in schizophrenia by restoring normal gamma oscillatory function. 

PMID- 25997998
TI  - Plasma peptidases as prognostic biomarkers in patients with first-episode
      psychosis.
AB  - The plasma activity of nine aminopeptidases was monitored over a year in first
      episode psychotic patients. We observed significant differences in aminopeptidase
      B (APB), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPPIV), but not in
      puromycin-sensitive aminopeptidase (PSA), prolyl endopeptidase (PEP), cysteine
      aminopeptidase (Cys-AP), aspartate aminopeptidase (Asp-AP), glutamate
      aminopeptidase (Glu) or piroglutamate aminopeptidase (PGI) in these patients
      compared to controls, and also a progressive increase in plasma activity,
      correlated to changes in scores on clinical scales, Global Assessment of
      Functioning scale (GAF) and Hamilton Depression Rating Scale (HDRS), at 1 month
      of follow-up. At 1 month after diagnosis, the median score obtained by patients
      on the GAF was negatively associated with the plasma activity of APB and PEP
      measured at the beginning of the psychotic episode, indicating a role as a
      negative prognostic factor that can predict psychiatric symptomatology. In the
      case of HDRS, scores at 1 month after diagnosis were found to be positively
      associated with the initial plasma activity of DPPIV, APN and PSA, indicating
      that their initial elevation is a negative prognostic factor that can predict
      subsequent depressive symptomatology. Taken together, these results suggest a
      pathophysiological involvement of plasma peptidases and indicate that
      aminopeptidase activity can predict the course of first-episode psychosis
      patients, acting as a prognostic indicator. 

PMID- 25998000
TI  - Fermented foods, neuroticism, and social anxiety: An interaction model.
AB  - Animal models and clinical trials in humans suggest that probiotics can have an
      anxiolytic effect. However, no studies have examined the relationship between
      probiotics and social anxiety. Here we employ a cross-sectional approach to
      determine whether consumption of fermented foods likely to contain probiotics
      interacts with neuroticism to predict social anxiety symptoms. A sample of young
      adults (N=710, 445 female) completed self-report measures of fermented food
      consumption, neuroticism, and social anxiety. An interaction model, controlling
      for demographics, general consumption of healthful foods, and exercise frequency,
      showed that exercise frequency, neuroticism, and fermented food consumption
      significantly and independently predicted social anxiety. Moreover, fermented
      food consumption also interacted with neuroticism in predicting social anxiety.
      Specifically, for those high in neuroticism, higher frequency of fermented food
      consumption was associated with fewer symptoms of social anxiety. Taken together
      with previous studies, the results suggest that fermented foods that contain
      probiotics may have a protective effect against social anxiety symptoms for those
      at higher genetic risk, as indexed by trait neuroticism. While additional
      research is necessary to determine the direction of causality, these results
      suggest that consumption of fermented foods that contain probiotics may serve as
      a low-risk intervention for reducing social anxiety. 

PMID- 25998001
TI  - Taste identification used as a potential discriminative test among depression and
      Alzheimer's disease in elderly: A pilot study.
AB  - Major Depression and Alzheimer's disease (AD) are two diseases in the elderly
      characterized by an overlap of early symptoms including memory and emotional
      disorders. The identification of specific markers would facilitate their
      diagnosis. The aim of this study was to identify such markers by investigating
      gustatory function in depressed and AD patients. We included 20 patients with
      unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD
      and 24 healthy individuals. We investigated the cognitive profile (depression,
      global cognitive efficiency and social/physical anhedonia) and gustatory function
      (ability to identify four basic tastes and to judge their intensity and hedonic
      value) in all participants. We found that AD patients performed worse than
      healthy participants in the taste identification test (for the analysis of all
      tastants together); however, this was not the case for depressed patients. We
      found no significant differences among the three groups in their ability to
      evaluate the intensity and hedonic value of the four tastes. Overall, our
      findings suggest that a taste identification test may be useful to distinguish AD
      and healthy controls but further investigation is required to conclude whether
      such a test can differentiate AD and depressed patients. 

PMID- 25998002
TI  - Differences of biased recall memory for emotional information among children and
      adolescents of mothers with MDD, children and adolescents with MDD, and normal
      controls.
AB  - This study examines explicit memory bias for emotional information in children
      and adolescents with major depressive disorder (MDD). Participants were a
      convenient sample of 28 children and adolescents of mothers with MDD, 28 children
      and adolescents with MDD, and 29 healthy controls. Their age range was 11-17
      years old. The groups were matched for gender ratio, mean age, and the years of
      educational level. They were assessed by the Recall Task. Emotional stimuli
      consisted of three sets of words namely sad, happy, and neutral words. Children
      and adolescents of mothers with MDD similar to children and adolescents with MDD
      recalled more sadness stimuli in comparison with the controls. In other words,
      they showed an explicit memory bias towards sad stimuli. Also, healthy children
      significantly recalled more happy words than the other two groups. There was no
      significant difference among the three groups for the recall of neutral stimuli.
      Current findings support that there is a recall memory bias for emotional
      information in children with MDD. These children more than healthy children
      recall sad words. Moreover, healthy children recall happy words more than
      children with MDD. 

PMID- 25998003
TI  - Punctal Plug Retention Rates for the Treatment of Moderate to Severe Dry Eye: A
      Randomized, Double-Masked, Controlled Clinical Trial.
AB  - PURPOSE: To compare retention rates of Super Flex (Eagle Vision, Memphis,
      Tennessee, USA; Softplug-Oasis Medical Inc, Glendora, California, USA) vs Parasol
      (Odyssey Medical, Memphis, Tennessee, USA; Beaver Visitec International, Waltham,
      Massachusetts, USA) punctal plugs. DESIGN: Randomized, double-masked,
      interventional controlled clinical trial. METHODS: Institutional study at Hotel
      Dieu Hospital (Queen's University) of 50 eyes, from patients with moderate to
      severe dry eye. Each eye from eligible patients was separately randomized to
      receive Super Flex or Parasol punctal plugs. The main outcome measure was plug
      retention at 6 months. Secondary outcome measures included objective tests of
      Schirmer I (mm), tear meniscus height (mm), tear break-up time (s), inferior
      fluorescein corneal staining (National Eye Institute [NEI] scale), and average
      lissamine green conjunctival staining (NEI scale). RESULTS: Punctal plug
      retention was significantly different at 6 months (P = .011). Sixty-eight percent
      of Parasol plugs were retained compared to 32% of Super Flex plugs. Parasol plugs
      required less frequent artificial tear use at 6 months (P = .024). There was a
      statistically significant improvement in all secondary outcome measures
      (Schirmer, tear meniscus height, tear break-up time, fluorescein corneal
      staining) at 6 months within plug groups except conjunctival staining. There were
      no additional significant differences between groups and no plug complications
      reported. CONCLUSIONS: Punctal plugs improve symptoms of moderate to severe dry
      eye; however, retention rates differ significantly. These data will allow us to
      guide patient decision making for the safe and effective treatment of punctal
      plugs for moderate to severe dry eye.

PMID- 25998004
TI  - High variability among Emergency Departments in 3rd-generation cephalosporins and
      fluoroquinolones use for community-acquired pneumonia.
AB  - OBJECTIVE: Fluoroquinolones and 3rd-generation cephalosporins that are prescribed
      for pneumonia may be avoided and replaced by a penicillin in some cases. We aimed
      to determine if the proportion of patients treated for pneumonia with a
      cephalosporin, a fluoroquinolone or both varies among Emergency Departments
      (EDs), and to estimate the proportion of avoidable prescriptions. METHODS: This
      was a retrospective study of patients treated for pneumonia in eight French EDs,
      and subsequently hospitalized in non-ICU wards. Third-generation cephalosporins
      or respiratory fluoroquinolones were presumed unavoidable if they met both
      criteria: (1) age >=65 years or comorbid condition; and (2) allergy or
      intolerance to penicillin, or failure of penicillin, or previous treatment with
      penicillin, or for fluoroquinolones only, suspected legionellosis. RESULTS: We
      included 832 patients. Thirty-four percent (95 % CI, 31-38 %) of patients were
      treated with a cephalosporin, a respiratory fluoroquinolone or both (range among
      EDs 19-44 %). Four EDs were independent risk factors for prescription of a
      cephalosporin, a fluoroquinolone or both [adjusted OR, 2.27 (1.64-3.15)], as were
      immune compromise [aOR 2.54 (1.56-4.14)], antibacterial therapy started before
      arrival in the ED [aOR 3.32 (2.30-4.81)], REA-ICU class III or IV [aOR 1.93 (1.15
      3.23)], PSI class V [aOR 1.49 (1.00-2.20)], fluid resuscitation [aOR 3.98 (2.49
      6.43)] and non-invasive ventilation in the ED [aOR, 7.18 (1.7-50.1)]. Treatment
      with a cephalosporin, a fluoroquinolone or both was avoidable in 67 % (62-73 %)
      of patients. CONCLUSION: Cephalosporins and fluoroquinolones use in pneumonia is
      highly variable among EDs. The majority of these prescriptions are avoidable.
      Antibiotic stewardship programs should be implemented to restrict their use in
      EDs.

PMID- 25998006
TI  - Personal electronic health records: understanding user requirements and needs in
      chronic cancer care.
AB  - BACKGROUND: The integration of new information and communication technologies
      (ICTs) is becoming increasingly important in reorganizing health care. Adapting
      ICTs as supportive tools to users' needs and daily practices is vital for
      adoption and use. OBJECTIVE: In order to develop a Web-based personal electronic
      health record (PEPA), we explored user requirements and needs with regard to
      desired information and functions. METHODS: A qualitative study across health
      care sectors and health professions was conducted in a regional health care
      setting in Germany. Overall, 10 semistructured focus groups were performed,
      collecting views of 3 prospective user groups: patients with colorectal cancer
      (n=12) and representatives from patient support groups (n=2), physicians (n=17),
      and non-medical HCPs (n=16). Data were audio- and videotaped, transcribed
      verbatim, and thematically analyzed using qualitative content analysis. RESULTS:
      For both patients and HCPs, it was central to have a tool representing the
      chronology of illness and its care processes, for example, patients wanted to
      track their long-term laboratory findings (eg, tumor markers). Designing health
      information in a patient accessible way was highlighted as important. Users
      wanted to have general and tumor-specific health information available in a PEPA.
      Functions such as filtering information and adding information by patients (eg,
      on their well-being or electronic communication with HCPs via email) were
      discussed. CONCLUSIONS: In order to develop a patient/user centered tool that is
      tailored to user needs, it is essential to address their perspectives. A
      challenge for implementation will be how to design PEPA's health data in a
      patient accessible way. Adequate patient support and technical advice for users
      have to be addressed.

PMID- 25998005
TI  - Endothelial cells direct human mesenchymal stem cells for osteo- and chondro
      lineage differentiation through endothelin-1 and AKT signaling.
AB  - INTRODUCTION: Human mesenchymal stem cells (hMSCs) reside in a perivascular niche
      of the body, suggesting that they interact closely with vascular endothelial
      cells (ECs) through cell-cell interaction or paracrine signaling to maintain cell
      functions. Endothelin-1 (ET1) is a paracrine factor mainly secreted by ECs. We
      thus hypothesize that ECs can regulate cellular activities of hMSCs and direct
      their stem cell fate. METHODS: We investigated whether co-cultured human aortic
      endothelial cells (HAECs) were able to regulate expression of potency- and
      lineage-related markers in bone marrow-derived hMSCs. We further explored the
      regulatory effects of ET1 on cell proliferation, expression of surface antigens
      and pluripotency-related markers, and multilineage differentiation in hMSCs.
      Activation of the AKT signaling pathway in hMSCs was also analyzed to identify
      its mechanistic role in the ET1-induced regulation. RESULTS: Co-cultured HAECs
      enhanced expression of mesenchymal lineage-related markers in hMSCs. Treatment of
      ET receptor antagonist downregulated the increased expression of CBFA1 in hMSCs
      cultured with HAEC-conditioned medium. hMSCs treated with ET1 showed cell
      proliferation and expression of surface antigens, CD73, CD90, and CD105,
      comparable with those without ET1 treatment. ET1-treated hMSCs also expressed
      upregulated mRNA transcript levels of OCT3/4, NANOG, CBFA1 and SOX9. When induced
      for lineage-specific differentiation, hMSCs pre-treated with ET1 showed enhanced
      osteogenesis and chondrogenesis. However, adipogenic differentiation of hMSCs was
      not affected by ET1 pretreatment. We further showed that the ET1-induced
      regulation was mediated by activation of AKT signaling. CONCLUSION: Our results
      demonstrate that ET1 secreted by HAECs can direct bone marrow-derived hMSCs for
      osteo- and chondro-lineage differentiation through activation of the AKT
      signaling pathway, suggesting that ET1 plays a crucial role in regulation of hMSC
      activity. Our findings may help understand how hMSCs interact with ECs in a
      perivascular niche.

PMID- 25998007
TI  - *informatics: Identifying and Tracking Informatics Sub-Discipline Terms in the
      Literature.
AB  - OBJECTIVE: To identify the breadth of informatics sub-discipline terms used in
      the literature for enabling subsequent organization and searching by sub
      discipline. METHODS: Titles in five literature sources were analyzed to extract
      terms for informatics sub-disciplines: 1) United States (U.S.) Library of
      Congress Online Catalog, 2) English Wikipedia, 3) U.S. National Library of
      Medicine (NLM) Catalog, 4) PubMed, and 5) PubMed Central. The extracted terms
      were combined and standardized with those in four vocabulary sources to create an
      integrated list: 1) Library of Congress Subject Headings (LCSH), 2) Medical
      Subject Headings (MeSH), 3) U.S. National Cancer Institute Thesaurus (NCIt), and
      4) EMBRACE Data and Methods (EDAM). Searches for terms in titles from each
      literature source were conducted to obtain frequency counts and start years for
      characterizing established and potentially emerging sub-disciplines. RESULTS:
      Analysis of 6,949 titles from literature sources and 67 terms from vocabulary
      sources resulted in an integrated list of 382 terms for informatics sub
      disciplines mapped to 292 preferred terms. In the last five decades,
      "bioinformatics", "medical informatics", "health informatics", "nursing
      informatics", and "biomedical informatics" were associated with the most
      literature. In the current decade, potentially emerging sub-disciplines include
      "disability informatics", "neonatal informatics", and "nanoinformatics" based on
      literature from the last five years. CONCLUSIONS: As the field of informatics
      continues to expand and advance, keeping up-to-date with historical and current
      trends will become increasingly challenging. The ability to track the
      accomplishments and evolution of a particular sub-discipline in the literature
      could be valuable for supporting informatics research, education, and training.

PMID- 25998008
TI  - pH switchable anion transport by an oxothiosquaramide.
AB  - An oxothiosquaramide was shown to bind to chloride through hydrogen bonding
      interactions in DMSO and found to exhibit pH switchable choride transport across
      phospholipid bilayers via an antiport transport mechanism. 

PMID- 25998009
TI  - Evaluation of Micronuclei, Nuclear Anomalies and the Nuclear/Cytoplasmic Ratio of
      Exfoliated Cervical Epithelial Cells in Genital Candidiasis.
AB  - OBJECTIVE: Candida is the most common cause of fungal infections. The aim of this
      study was to fill the gaps in the current knowledge on the frequencies of
      micronuclei and nuclear anomalies, and the nucleus/cytoplasmic ratio in genital
      candidiasis. STUDY DESIGN: A total of 88 Papanicolaou- stained cervical smears,
      which comprised Candida spp. (n = 44) and control cases with no infectious agent
      (n = 44), were studied. In each smear, cells with micronuclei and nuclear
      anomalies were counted in 1,000 epithelial cells and also nuclear and cellular
      areas were evaluated using image analysis software at a magnification of *400.
      RESULTS: The frequencies of micronucleated and binucleated cells and cells with
      perinuclear halos, and the nucleus/cytoplasmic ratio of epithelial cells were
      higher in the Candida-infected group compared with the control group (p < 0.05).
      CONCLUSIONS: Genital candidiasis is able to induce changes in the size and shape
      of epithelial cells. The nuclear/cytoplasmic ratio and the frequency of
      micronuclei may reflect the DNA damage in the cervical epithelium. Micronucleus
      scoring could be used to screen the genomic damage profile of epithelial cells in
      candidiasis.

PMID- 25998011
TI  - Final program forty third annual meeting international neuropsychological society
      february 4-7, 2015 denver, colorado, USA.

PMID- 25998010
TI  - Perception and evaluation of women's bodies in adolescents and adults with
      anorexia nervosa.
AB  - Body image disturbance in anorexia nervosa (AN) has been widely studied with
      regard to the patient's own body, but little is known about perception of or
      attitude towards other women's bodies in AN. The aim of the present study was to
      investigate how 20 girls aged 12-18 years and 19 adult women suffering from AN
      compared to 37 healthy adolescent girls and women estimate weight and
      attractiveness of women's bodies belonging to different BMI categories (BMI 13.8
      61.3 kg/m2). Weight and attractiveness ratings of the participant's own body and
      information on physical comparisons were obtained, and effects on others' weight
      and attractiveness ratings investigated. Differential evaluation processes were
      found: AN patients estimated other women's weight higher than control
      participants. Patients showed a bias towards assessing extremely underweight
      women as more attractive and normal weight and overweight women as less
      attractive than healthy girls and women. These effects were more pronounced in
      adult than in adolescent AN patients. The tendency to engage in physical
      comparison with others significantly correlated with weight as well as
      attractiveness ratings in patients. A logistic regression model encompassing own
      attractiveness ratings, attractiveness bias towards strongly underweight others'
      bodies and the interaction of this bias with age as predictors differentiated
      best between AN patients and controls. Our results indicate that females
      suffering from AN and healthy girls and women perceive other women's bodies
      differently. Assessment of others' weight and attractiveness may contribute to
      the maintenance of dysfunctional physical comparison processes.

PMID- 25998012
TI  - Evaluation of Quantitative Fluorescence in situ Hybridization for Relative
      Measurement of Telomere Length in Placental Mesenchymal Core Cells.
AB  - BACKGROUND: Reduced telomere length in placental mesenchymal core cells has been
      reported during pregnancies complicated by intrauterine growth restriction. To
      estimate telomere length, a precise, accurate and reproducible technique must be
      used. OBJECTIVE: We evaluated the characteristics of a quantitative fluorescence
      in situ hybridization (Q-FISH) technique for measuring relative telomere length
      in placental mesenchymal core cells. METHODS: From late chorionic villus
      samplings, telomere length in placental mesenchymal core cells was estimated by a
      Q-FISH technique using peptide nucleic acid telomere probes. The main
      characteristics of the Q-FISH technique, such as precision and reproducibility,
      were evaluated. RESULTS: The telomere length of the cultured placental
      mesenchymal cells did not follow a normal distribution. When the Q-FISH technique
      was performed on interphase nuclei of uncultured mesenchymal core cells, normal
      telomere length distribution was observed. The precision of the technique when
      applied to cultured placental mesenchymal core cells was estimated to be <6%, and
      its reproducibility ranged from to 92.9 to 104.7%. CONCLUSION: Our results showed
      that cell culture of placental villi produced a non-normal telomere length
      distribution, probably related to telomere DNA replication during the cell cycle.
      Despite the influence of cell culture, the Q-FISH technique reported herein
      showed good precision and reproducibility.

PMID- 25998013
TI  - Down-regulation of crambe fatty acid desaturase and elongase in Arabidopsis and
      crambe resulted in significantly increased oleic acid content in seed oil.
AB  - High oleic oil is an important industrial feedstock that has been one of the main
      targets for oil improvement in a number of oil crops. Crambe (Crambe abyssinica)
      is a dedicated oilseed crop, suitable for industrial oil production. In this
      study, we down-regulated the crambe fatty acid desaturase (FAD) and fatty acid
      elongase (FAE) genes for creating high oleic seed oil. We first cloned the crambe
      CaFAD2, CaFAD3 and CaFAE1 genes. Multiple copies of each of these genes were
      isolated, and the highly homologous sequences were used to make RNAi constructs.
      These constructs were first tested in Arabidopsis, which led to the elevated
      oleic or linoleic levels depending on the genes targeted, indicating that the
      RNAi constructs were effective in regulating the expression of the target genes
      in nonidentical but closely related species. Furthermore, down-regulation of
      CaFAD2 and CaFAE1 in crambe with the FAD2-FAE1 RNAi vector resulted in even more
      significant increase in oleic acid level in the seed oil with up to 80% compared
      to 13% for wild type. The high oleic trait has been stable in subsequent five
      generations and the GM line grew normally in greenhouse. This work has
      demonstrated the great potential of producing high oleic oil in crambe, thus
      contributing to its development into an oil crop platform for industrial oil
      production. 

PMID- 25998014
TI  - Two-Year Outcomes After Primary Anatomic Coracoclavicular Ligament
      Reconstruction.
AB  - PURPOSE: The purpose of this study was to report the clinical and structural
      outcomes after anatomic coracoclavicular ligament reconstruction (ACCR) with free
      tendon allografts in patients with grade III and grade V acromioclavicular (AC)
      joint dislocations. METHODS: Thirty-one shoulders underwent primary ACCR with
      tendon allografts for Rockwood grade III and grade V AC joint dislocations.
      Preoperative data included patient demographic characteristics, injury
      characteristics, and surgical history, along with American Shoulder and Elbow
      Surgeons (ASES) scores, Short Form 12 Physical Component Summary (SF-12 PCS)
      scores, and various pain scales. Outcome measures were also collected a minimum
      of 2 years postoperatively with the addition of Quick Disabilities of the Arm,
      Shoulder and Hand (QuickDASH) scores; Single Assessment Numeric Evaluation (SANE)
      scores; and patient satisfaction. In addition, preoperative and postoperative
      coracoclavicular distances were analyzed using standard anteroposterior
      radiographs. RESULTS: ACCR was performed in 31 patients (31 shoulders) with a
      mean age of 43.9 years (range, 21 to 71 years). In 7 patients (22.6%) a
      complication occurred that required a subsequent surgical procedure including
      graft rupture/attenuation (2), clavicle fractures (2), distal clavicle
      hypertrophy (2), and adhesive capsulitis (1). Of the remaining 24 patients, 20
      (83.3%) had subjective outcome data available after a minimum 2-year follow-up
      period (mean, 3.5 years; range, 2.0 to 6.2 years). The mean postoperative ASES
      and SF-12 PCS scores significantly improved when compared with the preoperative
      baseline values (58.9 v 93.8 for ASES scores [P < .001] and 45.3 v 54.4 for SF-12
      PCS scores [P = .007]). At final follow-up, the SANE and QuickDASH scores were
      89.1 and 5.6, respectively, with a median patient satisfaction rating of 9 of 10.
      CONCLUSIONS: Patients who did not require revision surgery showed excellent
      postoperative outcome scores: The mean ASES score was 93.8, the mean SANE score
      was 89.1, and the mean QuickDASH score was 5.6, with a median patient
      satisfaction rating of 9 of 10. Further study regarding ACCR techniques should
      focus on decreasing the risks of complications and maintaining reduction of the
      AC joint. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 25998015
TI  - Arthroscopic Treatment of Labral Tears in Patients Aged 60 Years or Older.
AB  - PURPOSE: The purpose of this study was to (1) evaluate the clinical outcomes of a
      series of patients aged 60 years or older who underwent hip arthroscopy for
      labral tears with minimum 2-year follow-up and (2) identify risk factors for
      conversion to total hip arthroplasty (THA). METHODS: Outcome data were
      prospectively collected and retrospectively reviewed in patients aged 60 years or
      older who underwent hip arthroscopy between April 2008 and May 2012. Four patient
      reported outcome (PRO) scores, pain scores, and satisfaction ratings were
      collected. Conversion to THA and revision surgery rates were recorded. A subgroup
      analysis compared survivors with patients requiring THA. RESULTS: Minimum 2-year
      follow-up was available for 30 patients with a mean age of 63.9 years. The 2-year
      survivorship rate was 70%, with 9 patients undergoing conversion to THA at a mean
      of 1.1 years after hip arthroscopy. Two patients required additional surgery
      during the study period, for a reoperation rate of 37% (11 of 30 patients). The
      remaining cohort showed mean improvements in all PRO scores. All scores, except
      the sports-related PRO (P = .12), improved significantly from the preoperative
      baseline scores. Visual analog scale scores for pain decreased from a mean of 5.0
      preoperatively to 2.7 postoperatively (P = .003). Patients who required
      conversion to THA had lower preoperative modified Harris Hip Scores (P = .015),
      lower preoperative Hip Outcome Score-Activity of Daily Living values (P = .01),
      higher pain scores (P = .05), greater acetabular inclination (P = .023), and more
      severe chondral damage (P = .033). CONCLUSIONS: Arthroscopic treatment of labral
      tears in patients aged 60 years or older should be approached with caution.
      Patients in this age group had an overall 2-year survivorship rate of 70% and
      should be counseled before surgery on the possibility of subsequent conversion to
      THA. Patients aged 60 years or older with poor preoperative PRO scores, high pain
      scores, radiographic evidence of borderline dysplasia, and severe chondral damage
      may be poor candidates for hip arthroscopy. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 25998016
TI  - Is Local Viscosupplementation Injection Clinically Superior to Other Therapies in
      the Treatment of Osteoarthritis of the Knee: A Systematic Review of Overlapping
      Meta-analyses.
AB  - PURPOSE: To conduct a systematic review of overlapping meta-analyses comparing
      treatment of knee osteoarthritis (OA) with intra-articular viscosupplementation
      (intra-articular hyaluronic acid [IA-HA]) versus oral nonsteroidal anti
      inflammatory drugs (NSAIDs), intra-articular corticosteroids (IA
      corticosteroids), intra-articular platelet-rich plasma (IA-PRP), or intra
      articular placebo (IA-placebo) to determine which meta-analyses provide the best
      current evidence and identify potential causes of discordance. METHODS:
      Literature searches were performed for meta-analyses examining use of IA-HA
      versus NSAIDs, IA-corticosteroids, IA-PRP, or IA-placebo. Clinical data were
      extracted, and meta-analysis quality was assessed. The Jadad algorithm was
      applied to determine which meta-analyses provided the highest level of evidence.
      RESULTS: Fourteen meta-analyses met the eligibility criteria and ranged in
      quality from Level I to IV evidence. In studies reporting patient numbers, there
      were a total of 20,049 patients: 13,698 receiving IA-HA, 355 receiving NSAIDs,
      294 receiving IA-corticosteroids, and 5,702 receiving IA-placebo. Ten studies
      examined the effects of IA-HA versus IA-placebo; of these, 5 found that IA-HA
      improved pain and 4 found that IA-HA improved function. No clinically relevant
      differences in the efficacy of IA-HA versus NSAIDs regarding pain and function
      were found. Regarding IA-HA versus IA-PRP, IA-HA improved knee function at 2 and
      6 months after injection but the effects were less robust than those of IA-PRP.
      Regarding IA-HA versus IA-corticosteroids, the positive effects of IA-HA were
      greater at 5 to 13 weeks and persisted for up to 26 weeks. After application of
      the Jadad algorithm, 2 concordant high-quality meta-analyses were selected and
      both showed that IA-HA provided clinically relevant improvements in pain and
      function compared with IA-placebo. CONCLUSIONS: This systematic review of
      overlapping meta-analyses comparing IA-HA with other nonoperative treatment
      modalities for knee OA shows that the current highest level of evidence suggests
      that IA-HA is a viable option for knee OA. Its use results in improvements in
      knee pain and function that can persist for up to 26 weeks. IA-HA has a good
      safety profile, and its use should be considered in patients with early knee OA.
      LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

PMID- 25998018
TI  - Millisecond-Timescale Monitoring of PbS Nanoparticle Nucleation and Growth Using
      Droplet-Based Microfluidics.
AB  - The early-time kinetics (<1 s) of lead sulfide (PbS) quantum dot formation are
      probed using a novel droplet-based microfluidic platform, which allows for high
      throughput and real-time optical analysis of the reactive process with
      millisecond time resolution. The reaction platform enables the concurrent
      investigation of the emission characteristics of PbS quantum dots and a real-time
      estimation of their size and concentration during nucleation and growth. These
      investigations reveal a two-stage mechanism for PbS nanoparticle formation. The
      first stage corresponds to the fast conversion of precursor species to PbS
      crystals, followed by the growth of the formed particles. The growth kinetics of
      the PbS nanoparticles follow the Lifshitz-Slyozov-Wagner model for Ostwald
      ripening, allowing direct estimation of the rate constants for the process. In
      addition, the extraction of absorption spectra of ultrasmall quantum dots is
      demonstrated for first time in an online manner. The droplet-based microfluidic
      platform integrated with online spectroscopic analysis provides a new tool for
      the quantitative extraction of high temperature kinetics for systems with rapid
      nucleation and growth stages. 

PMID- 25998017
TI  - Recombinant fragilysin isoforms cause E-cadherin cleavage of intact cells and do
      not cleave isolated E-cadherin.
AB  - The fragilysin (BFT) is a protein secreted by enterotoxigenic Bacteroides
      fragilis strains. BFT contains zinc-binding motif which was found in the
      metzincins family of metalloproteinases. In this study, we generated three known
      recombinant isoforms of BFT using Escherichia coli, tested their activity and
      examined whether E-cadherin is a substrate for BFTs. BFT treatment of HT-29 cells
      induced endogenous E-cadherin cleavage, and this BFT activity requires the native
      structure of zinc-binding motif. At the same time recombinant BFTs did not cleave
      recombinant E-cadherin or E-cadherin in isolated cell fractions. It indicates
      that E-cadherin may be not direct substrate for BFT. We also detected and
      identified proteins released into the cultural medium after HT-29 cells treatment
      with BFT. The role of these proteins in pathogenesis and cell response to BFT
      remains to be determined. 

PMID- 25998020
TI  - Concentrations in human blood of petroleum hydrocarbons associated with the
      BP/Deepwater Horizon oil spill, Gulf of Mexico.
AB  - During/after the BP/Deepwater Horizon oil spill, cleanup workers, fisherpersons,
      SCUBA divers, and coastal residents were exposed to crude oil and dispersants.
      These people experienced acute physiological and behavioral symptoms and
      consulted a physician. They were diagnosed with petroleum hydrocarbon poisoning
      and had blood analyses analyzed for volatile organic compounds; samples were
      drawn 5-19 months after the spill had been capped. We examined the petroleum
      hydrocarbon concentrations in the blood. The aromatic compounds m,p-xylene,
      toluene, ethylbenzene, benzene, o-xylene, and styrene, and the alkanes hexane, 3
      methylpentane, 2-methylpentane, and iso-octane were detected. Concentrations of
      the first four aromatics were not significantly different from US National Health
      and Nutritional Examination Survey/US National Institute of Standards and
      Technology 95th percentiles, indicating high concentrations of contaminants. The
      other two aromatics and the alkanes yielded equivocal results or significantly
      low concentrations. The data suggest that single-ring aromatic compounds are more
      persistent in the blood than alkanes and may be responsible for the observed
      symptoms. People should avoid exposure to crude oil through avoidance of the
      affected region, or utilizing hazardous materials suits if involved in cleanup,
      or wearing hazardous waste operations and emergency response suits if SCUBA
      diving. Concentrations of alkanes and PAHs in the blood of coastal residents and
      workers should be monitored through time well after the spill has been
      controlled.

PMID- 25998019
TI  - The future of host cell protein (HCP) identification during process development
      and manufacturing linked to a risk-based management for their control.
AB  - The use of biological systems to synthesize complex therapeutic products has been
      a remarkable success. However, during product development, great attention must
      be devoted to defining acceptable levels of impurities that derive from that
      biological system, heading this list are host cell proteins (HCPs). Recent
      advances in proteomic analytics have shown how diverse this class of impurities
      is; as such knowledge and capability grows inevitable questions have arisen about
      how thorough current approaches to measuring HCPs are. The fundamental issue is
      how to adequately measure (and in turn monitor and control) such a large number
      of protein species (potentially thousands of components) to ensure safe and
      efficacious products. A rather elegant solution is to use an immunoassay (enzyme
      linked immunosorbent assay [ELISA]) based on polyclonal antibodies raised to the
      host cell (biological system) used to synthesize a particular therapeutic
      product. However, the measurement is entirely dependent on the antibody serum
      used, which dictates the sensitivity of the assay and the degree of coverage of
      the HCP spectrum. It provides one summed analog value for HCP amount; a positive
      if all HCP components can be considered equal, a negative in the more likely
      event one associates greater risk with certain components of the HCP proteome. In
      a thorough risk-based approach, one would wish to be able to account for this.
      These issues have led to the investigation of orthogonal analytical methods; most
      prominently mass spectrometry. These techniques can potentially both identify and
      quantify HCPs. The ability to measure and monitor thousands of proteins
      proportionally increases the amount of data acquired. Significant benefits exist
      if the information can be used to determine critical HCPs and thereby create an
      improved basis for risk management. We describe a nascent approach to risk
      assessment of HCPs based upon such data, drawing attention to timeliness in
      relation to biosimilar initiatives. The development of such an approach requires
      databases based on cumulative knowledge of multiple risk factors that would
      require national and international regulators, standards authorities (e.g., NIST
      and NIBSC), industry and academia to all be involved in shaping what is the best
      approach to the adoption of the latest bioanalytical technology to this area,
      which is vital to delivering safe efficacious biological medicines of all types.

PMID- 25998021
TI  - TRPM8 is a neuronal osmosensor that regulates eye blinking in mice.
AB  - Specific peripheral sensory neurons respond to increases in extracellular
      osmolality but the mechanism responsible for excitation is unknown. Here we show
      that small increases in osmolality excite isolated mouse dorsal root ganglion
      (DRG) and trigeminal ganglion (TG) neurons expressing the cold-sensitive TRPM8
      channel (transient receptor potential channel, subfamily M, member 8).
      Hyperosmotic responses were abolished by TRPM8 antagonists, and were absent in
      DRG and TG neurons isolated from Trpm8(-/-) mice. Heterologously expressed TRPM8
      was activated by increased osmolality around physiological levels and inhibited
      by reduced osmolality. Electrophysiological studies in a mouse corneal
      preparation demonstrated that osmolality regulated the electrical activity of
      TRPM8-expressing corneal afferent neurons. Finally, the frequency of eye blinks
      was reduced in Trpm8(-/-) compared with wild-type mice and topical administration
      of a TRPM8 antagonist reduced blinking in wild-type mice. Our findings identify
      TRPM8 as a peripheral osmosensor responsible for the regulation of normal eye
      blinking in mice. 

PMID- 25998022
TI  - BWH emergency radiology-surgical correlation: intraperitoneal urinary bladder
      rupture.
AB  - We describe the radiological and intraoperative correlation of two cases of
      intraperitoneal bladder rupture: a 23-year-old man involved in a high-speed motor
      vehicle collision and a 49-year-old man with hematuria and abdominal pain after a
      night of heavy alcohol ingestion. Both patients underwent urgent exploratory
      laparotomies and repair of their bladder injuries. The purpose of this article is
      to emphasize the importance of understanding the different etiologies of bladder
      rupture and recognizing the imaging findings on computed tomography (CT) and CT
      cystography to help guide the surgeons in the patient's management. 

PMID- 25998024
TI  - Ginsenoside Rg3 induces apoptosis in human multiple myeloma cells via the
      activation of Bcl-2-associated X protein.
AB  - Ginsenoside Rg3 is one of the main constituents isolated from Panax ginseng, and
      exhibits cytotoxic effects against cancer cells. The present study aimed to
      investigate the effects of ginsenoside Rg3 on human multiple myeloma cells, and
      determine the underlying molecular mechanisms. The cells were exposed to
      ginsenoside Rg3 at various concentrations (0-80 uM) for 48 h. A subsequent cell
      proliferation assay demonstrated that treatment with ginsenoside Rg3 resulted in
      a dose-dependent inhibition of the proliferation of U266 and RPMI8226 cells.
      Furthermore, exposure to ginsenoside Rg3 led to a marked increase in the rate of
      apoptosis in the U266 cells, coupled with increased caspase-3 activity. The
      ginsenoside Rg3-treated cells also exhibited an elevation in the expression of B
      cell lymphoma 2-associated X protein (Bax), a pro-apoptotic protein. Notably,
      knockdown of Bax protected the U266 cells from Rg3-induced apoptosis. Overall,
      these findings suggested that ginsenoside Rg3 induced apoptosis in multiple
      myeloma cells, at least partially, through upregulation of the expression of Bax.

PMID- 25998023
TI  - Lifestyle factors and indices of kidney function in the Framingham Heart Study.
AB  - BACKGROUND AND OBJECTIVES: Lifestyle characteristics are modifiable factors that
      could be targeted as part of chronic kidney disease (CKD) prevention. We sought
      to determine the association of lifestyle characteristics with incident estimated
      glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) and rapid eGFR decline in
      older adults in the United States. METHODS: Prospective cohort study of
      Framingham Offspring participants with baseline eGFR <60 ml/min/1.73 m(2) (n =
      1,802) who attended the seventh (1998-2001; baseline) and eighth (2005-2008;
      follow-up) examinations (mean age = 59 years, 54.8% women). Predictors included
      measures of diet quality, physical activity, alcohol intake, and current smoking
      status assessed during baseline. Outcomes were based on creatinine-based eGFR at
      baseline and follow-up and included incident eGFR <60 ml/min/1.73 m(2) (at follow
      up) and rapid eGFR decline (annual eGFR decrease >=3 ml/min/1.73 m(2)). RESULTS:
      Over an average follow-up of 6.6 years, 9.5% (n = 171) of participants developed
      incident eGFR <60. A trend was observed across quartiles of diet quality, with
      higher levels of diet quality associated with a decreased odds ratio (OR) of
      incident eGFR <60 (p trend = 0.045). Higher diet quality was associated with
      decreased odds of rapid eGFR decline (p trend = 0.03) and was attenuated with
      additional adjustment (p trend = 0.07). In sensitivity analysis for rapid eGFR
      decline using a secondary definition (annual eGFR decrease >=3 and incident eGFR
      <60), diet associations remained significant with additional adjustment (p trend
      = 0.04). No associations were observed with physical activity, smoking status, or
      alcohol intake with incident eGFR <60 or rapid eGFR decline (all p > 0.19).
      CONCLUSIONS: Higher diet quality may be associated with a decreased risk of
      incident eGFR <60 ml/min/1.73 m(2), and rapid eGFR decline. Whether adherence to
      a healthy diet can prevent reduction in kidney function warrants further study.

PMID- 25998025
TI  - Increased production of BDNF in colonic epithelial cells induced by fecal
      supernatants from diarrheic IBS patients.
AB  - Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in
      pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome
      (IBS-D), but regulation on its expression remains unclear. We investigated the
      role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF
      expression in colonic epithelial cells of human and mice. Using human Caco-2
      cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein
      levels compared to control FSN, which were remarkably suppressed by the serine
      protease inhibitor. To further explore the potential mechanisms, we investigated
      the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found
      a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation.
      Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of
      BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-kappaB p65,
      contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we
      intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN
      significantly elevated colonic BDNF and visceral hypersensitivity in mice, which
      were both suppressed by the inhibitor of serine protease or antagonist of PAR-2.
      Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN
      promotes expression of colonic BDNF, thereby contributing to IBS-like visceral
      hypersensitivity. 

PMID- 25998026
TI  - Altered cytochrome P450 activities and expression levels in the liver and
      intestines of the monosodium glutamate-induced mouse model of human obesity.
AB  - Cytochromes P450 (CYPs) are enzymes present from bacteria to man involved in
      metabolism of endogenous and exogenous compounds incl. drugs. Our objective was
      to assess whether obesity leads to changes in activities and expression of CYPs
      in the mouse liver, small intestine and colon. MAIN METHODS: An obese mouse model
      with repeated injection of monosodium glutamate (MSG) to newborns was used.
      Controls were treated with saline. All mice were sacrificed at 8 months. In the
      liver and intestines, levels of CYP mRNA and proteins were analyzed using RT-PCR
      and Western blotting. Activities of CYP enzymes were measured with specific
      substrates of human orthologous forms. KEY FINDINGS: At the end of the
      experiment, body weight, plasma insulin and leptin levels as well as the specific
      content of hepatic CYP enzymes were increased in obese mice. Among CYP enzymes,
      hepatic CYP2A5 activity, protein and mRNA expression increased most significantly
      in obese animals. Higher activities and protein levels of hepatic CYP2E1 and 3A
      in the obese mice were also found. No or a weak effect on CYPs 2C and 2D was
      observed. In the small intestine and colon, no changes of CYP enzymes were
      detected except for increased expression of CYP2E1 and decreased expression of
      CYP3A mRNAs in the colon of the obese mice. SIGNIFICANCE: Results of our study
      suggest that the specific content and activities of some liver CYP enzymes
      (especially CYP2A5) can be increased in obese mice. Higher activity of CYP2A5
      (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of
      this enzyme (valproic acid, nicotine, methoxyflurane).

PMID- 25998027
TI  - Leptin: From structural insights to the design of antagonists.
AB  - After its discovery in 1994, it soon became clear that leptin acts as an
      adipocyte-derived hormone with a central role in the control of body weight and
      energy homeostasis. However, a growing body of evidence has revealed that leptin
      is a pleiotropic cytokine with activities on many peripheral cell types.
      Inappropriate leptin signaling can promote autoimmunity, certain cardiovascular
      diseases, elevated blood pressure and cancer, which makes leptin and the leptin
      receptor interesting targets for antagonism. Profound insights in the leptin
      receptor (LR) activation mechanisms are a prerequisite for the rational design of
      these antagonists. In this review, we focus on the molecular mechanisms
      underlying leptin receptor activation and signaling. We also discuss the current
      strategies to interfere with leptin signaling and their therapeutic potential. 

PMID- 25998028
TI  - The role of leptin in the sporadic form of Alzheimer's disease. Interactions with
      the adipokines amylin, ghrelin and the pituitary hormone prolactin.
AB  - Leptin (Lep) is emerging as a pivotal molecule involved in both the early events
      and the terminal phases of Alzheimer's disease (AD). In the canonical pathway,
      Lep acts as an anorexigenic factor via its effects on hypothalamic nucleus.
      However, additional functions of Lep in the hippocampus and cortex have been
      unravelled in recent years. Early events in the sporadic form of AD likely
      involve cellular level alterations which can have an effect on food intake and
      metabolism. Thus, AD can be conceivably interpreted as a multiorgan pathology
      that not only results in a dramatic neuronal loss in brain areas such as the
      hippocampus and the cortex (ultimately leading to a significant cognitive
      impairment) but as a disease which also affects body-weight homeostasis.
      According to this view, body-weight control disruptions are to be expected in
      both the early- and late-stage AD, concomitant with changes in serum Lep content,
      alterations in Lep transport across the blood-brain barrier (BBB) and Lep
      receptor-related signalling abnormalities. Lep is a member of the adipokine
      family of molecules, while the Lep receptor belongs to the class I cytokine
      receptors. Since cellular response to adipokine signalling can be either
      potentiated or diminished as a result of specific ligand-receptor interactions,
      Lep interactions with other members of the adipokine family including amylin,
      ghrelin and hormones such as prolactin require further investigation. In this
      review, we provide a general perspective on the functions of Lep in the brain,
      with a particular focus on the sporadic AD.

PMID- 25998029
TI  - Leptin resistance in obesity: An epigenetic landscape.
AB  - Leptin is an adipocyte-secreted hormone that inhibits food intake and stimulates
      energy expenditure through interactions with neuronal pathways in the brain,
      particularly pathways involving the hypothalamus. Intact functioning of the
      leptin route is required for body weight and energy homeostasis. Given its
      function, the discovery of leptin increased expectations for the treatment of
      obesity. However, most obese individuals and subjects with a predisposition to
      regain weight after losing it have leptin concentrations than lean individuals,
      but despite the anorexigenic function of this hormone, appetite is not
      effectively suppressed in these individuals. This phenomenon has been deemed
      leptin resistance and could be the result of impairments at a number of levels in
      the leptin signalling pathway, including reduced access of the hormone to its
      receptor due to changes in receptor expression or changes in post-receptor signal
      transduction. Epigenetic regulation of the leptin signalling circuit could be a
      potential mechanism of leptin function disturbance. This review discusses the
      molecular mechanisms, particularly the epigenetic regulation mechanisms, involved
      in leptin resistance associated with obesity and the therapeutic potential of
      these molecular mechanisms in the battle against the obesity pandemic. 

PMID- 25998030
TI  - Cognitive performance during the first year of treatment in first-episode
      schizophrenia: a case-control study.
AB  - BACKGROUND: Several questions remain unanswered regarding the magnitude and time
      course of cognitive improvement in response to antipsychotic treatment. The
      purpose of this study was to assess changes in cognitive performance in
      antipsychotic-naive or minimally medicated patients with first-episode
      schizophrenia during the first 12 months of treatment, in a case-control design.
      Patients were treated with flupenthixol decanoate depot injection, according to a
      standard algorithm. The primary outcome measure was change in MATRICS Cognitive
      Consensus Battery (MCCB) composite score over 12 months. METHOD: The sample
      comprised 92 patients and 100 healthy controls matched for age, sex, ethnicity
      and educational status. Cognitive function was assessed by means of the MCCB.
      RESULTS: A mixed-effects model identified a significant group * time effect (p <=
      0.0001) for the MCCB composite score, with patients showing a greater degree of
      change than the controls. For the other MCCB domains there were significant group
      * time effects at adjusted significance level for attention and vigilance (p <=
      0.0001), visual learning (p <= 0.0001), verbal learning (p = 0.005) and working
      memory (p <= 0.0001), but not for reasoning and problem solving (p = 0.04), speed
      of processing (p = 0.03) and social cognition (p = 0.06). There were moderate
      correlations between change in MCCB composite score and change in symptomatology
      as assessed by Positive and Negative Syndrome Scale factor analysis-derived
      domains. CONCLUSIONS: Substantial improvements in cognitive function were
      observed over and above a practice effect, and were significantly correlated with
      improvements in psychopathology and functionality.

PMID- 25998031
TI  - Does elevation of serum creatinine in patients with chronic hepatitis C under
      therapy of telaprevir mean renal impairment?
AB  - AIM: Treatment with telaprevir (TVR) entails adverse side-effects including
      anaemia and elevation of serum creatinine (SCr) level. Our purpose was to
      evaluate the effects of treatment with TVR on renal function in adults with
      chronic hepatitis C. METHODS: Thirteen adult patients with HCV genotype 1b who
      were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and
      ribavirin (RBV) were prospectively followed. Patients were divided into two
      groups: (i) patients with an increase in SCr during the treatment (n = 8), and
      (ii) patients without an increase in SCr (n = 5). Urine and serum parameters were
      evaluated. RESULTS: Although there was no difference in SCr level between the two
      groups before HCV therapy, the SCr level was persistently high in the patients in
      the increase-in-SCr group during the triple therapy. The SCr level returned to
      the pre-treatment level after cessation of TVR. There were no differences in
      urinary L-FABP, NAG, serum cystatin C level and eGFRcys throughout the study
      between the two groups. The serum cystatin C level at pre-treatment tended to be
      higher in the increase-in-SCr group. Urinary L-FABP and NAG levels in these
      groups remained within normal limits during treatment. We found that the increase
      in SCr was not associated with the degree of renal impairment. The increase in
      SCr may have been induced as a result of a decrease in creatinine secretion from
      proximal tubules via inhibition of transporters of creatinine induced by TVR.
      CONCLUSION: Elevation of SCr levels with TVR therapy may not suggest renal
      impairment.

PMID- 25998032
TI  - Deregulation of energetic metabolism in the clear cell renal cell carcinoma: A
      multiple pathway analysis based on microarray profiling.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney
      cancer. In order to better understand the biology of ccRCC, we accomplished the
      gene profiling of fresh tissue specimens from 11 patients with the renal tumors
      (9 ccRCCs, 1 oncocytoma and 1 renal B-lymphoma), in which the tumor-related data
      were compared to the paired healthy kidney tissues from the same patients. All
      ccRCCs exhibited a considerably elevated transcription of the gene coding for
      carbonic anhydrase IX (CAIX). Moreover, the ccRCC tumors consistently displayed
      increased expression of genes encoding the glycolytic pathway enzymes, e.g.
      hexokinase II (HK2) and lactate dehydrogenase A (LDHA) and a decreased expression
      of genes for the mitochondrial electron transport chain components, indicating an
      overall reprogramming of the energetic metabolism in this tumor type. This
      appears to be accompanied by altered expression of the genes of the pH regulating
      machinery, including ion and lactate transporters. Immunohistochemical staining
      of tumor tissue sections confirmed the increased expression of CAIX, HK2 and LDHA
      in ccRCC, validating the microarray data and supporting their potential as the
      energetic metabolism-related biomarkers of the ccRCC. 

PMID- 25998033
TI  - The Effects of Oxygen Therapy on Myocardial Salvage in ST Elevation Myocardial
      Infarction Treated with Acute Percutaneous Coronary Intervention: The
      Supplemental Oxygen in Catheterized Coronary Emergency Reperfusion (SOCCER)
      Study.
AB  - OBJECTIVES: Despite a lack of scientific evidence, oxygen has long been a part of
      standard treatment for patients with acute myocardial infarction (AMI). However,
      several studies suggest that oxygen therapy may have negative cardiovascular
      effects. We here describe a randomized controlled trial, i.e. Supplemental Oxygen
      in Catheterized Coronary Emergency Reperfusion (SOCCER), aiming to evaluate the
      effect of oxygen therapy on myocardial salvage and infarct size in patients with
      ST elevation myocardial infarction (STEMI) treated with a primary percutaneous
      coronary intervention (PCI). METHODS: One hundred normoxic STEMI patients
      accepted for a primary PCI are randomized in the ambulance to either standard
      oxygen therapy or no supplemental oxygen. All patients undergo cardiovascular
      magnetic resonance imaging (CMR) 2-6 days after the primary PCI, and a subgroup
      of 50 patients undergo an extended echocardiography during admission and at 6
      months. All patients are followed for 6 months for hospital admission for heart
      failure and subjective perception of health. The primary endpoint is the
      myocardial salvage index on CMR. DISCUSSION: Even though oxygen therapy is a part
      of standard care, oxygen may not be beneficial for patients with AMI and is
      possibly even harmful. The results of the present and concurrent oxygen trials
      may change international treatment guidelines for patients with AMI or ischemia.

PMID- 25998034
TI  - Into the looking glass: Broadening models to explain the spectrum of sensory and
      affective vicarious experiences.
AB  - Ward and Bannisy's proposed conceptual framework-Threshold Theory and Self-Other
      Theory-for mirror touch synesthesia are welcomed as an explanation of mechanisms
      giving rise to innocuous vicarious phenomena. Herein we propose that these
      vicarious, or synesthetic, experiences should be considered along a spectrum of
      experiences, from innocuous through to noxious or threatening sensations. In
      particular, we would like to see these theories considered within a broader
      framework to explain the multitude of vicarious experiences that seem to share
      fundamental neurophysiological and trait characteristics. 

PMID- 25998035
TI  - A pragmatic randomised controlled trial of an implementation intervention to
      increase healthy eating and physical activity-promoting policies, and practices
      in centre-based childcare services: study protocol.
AB  - BACKGROUND: Promotion of healthy eating and physical activity in early childhood
      is recommended as a global chronic disease prevention strategy. Centre-based
      childcare services represent a promising setting to provide children with
      opportunities to improve healthy eating and physical activity. Evidence to inform
      implementation of childcare obesity prevention guidelines into routine practice
      in childcare, however, is lacking. This study aims to assess the effectiveness of
      an intervention, delivered to childcare staff, aiming to increasing service
      implementation of healthy eating and physical activity-promoting policies and
      practices. METHODS AND ANALYSIS: A pragmatic parallel group randomised controlled
      trial will be undertaken with 165 childcare services in the Hunter New England
      region of New South Wales, Australia. Services will be randomised to receive
      either a 10-month evidence-based performance review intervention with other
      resources to support practice change, or to a waitlist control group. The primary
      trial outcome is the proportion of services implementing all of the following
      recommended healthy eating and physical activity promoting practices: written
      nutrition, physical activity and small screen recreation policies; providing
      information to families regarding healthy eating (including breastfeeding),
      physical activity and small screen time; providing twice weekly healthy eating
      learning experiences to children; providing water and only plain milk to
      children; providing fundamental movement skills activities for children every
      day; and limiting and using electronic screen time more for educational purposes
      and learning experiences. Effectiveness will be assessed using a telephone
      interview of practice implementation with childcare staff at baseline and 12
      months following baseline. ETHICS AND DISSEMINATION: The study was approved by
      the Hunter New England Human Research Ethics Committee and the University of
      Newcastle Human Research Ethics Committee. Study findings will be disseminated
      widely through peer-reviewed publications and conference presentations. TRIAL
      REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry
      ACTRN12614000972628.

PMID- 25998036
TI  - Mood instability is a common feature of mental health disorders and is associated
      with poor clinical outcomes.
AB  - OBJECTIVES: Mood instability is a clinically important phenomenon but has
      received relatively little research attention. The objective of this study was to
      assess the impact of mood instability on clinical outcomes in a large sample of
      people receiving secondary mental healthcare. DESIGN: Observational study using
      an anonymised electronic health record case register. SETTING: South London and
      Maudsley NHS Trust (SLaM), a large provider of inpatient and community mental
      healthcare in the UK. PARTICIPANTS: 27,704 adults presenting to SLaM between
      April 2006 and March 2013 with a psychotic, affective or personality disorder.
      EXPOSURE: The presence of mood instability within 1 month of presentation,
      identified using natural language processing (NLP). MAIN OUTCOME MEASURES: The
      number of days spent in hospital, frequency of hospital admission, compulsory
      hospital admission and prescription of antipsychotics or non-antipsychotic mood
      stabilisers over a 5-year follow-up period. RESULTS: Mood instability was
      documented in 12.1% of people presenting to mental healthcare services. It was
      most frequently documented in people with bipolar disorder (22.6%), but was
      common in people with personality disorder (17.8%) and schizophrenia (15.5%). It
      was associated with a greater number of days spent in hospital (beta coefficient
      18.5, 95% CI 12.1 to 24.8), greater frequency of hospitalisation (incidence rate
      ratio 1.95, 1.75 to 2.17), greater likelihood of compulsory admission (OR 2.73,
      2.34 to 3.19) and an increased likelihood of prescription of antipsychotics
      (2.03, 1.75 to 2.35) or non-antipsychotic mood stabilisers (2.07, 1.77 to 2.41).
      CONCLUSIONS: Mood instability occurs in a wide range of mental disorders and is
      not limited to affective disorders. It is generally associated with relatively
      poor clinical outcomes. These findings suggest that clinicians should screen for
      mood instability across all common mental health disorders. The data also suggest
      that targeted interventions for mood instability may be useful in patients who do
      not have a formal affective disorder.

PMID- 25998037
TI  - The dose-response association of urinary metals with altered pulmonary function
      and risks of restrictive and obstructive lung diseases: a population-based study
      in China.
AB  - OBJECTIVE: Reduced pulmonary function is an important predictor of environment
      related pulmonary diseases; however, evidence of an association between exposures
      to various metals from all possible routes and altered pulmonary function is
      limited. We aimed to investigate the association of various metals in urine with
      pulmonary function, restrictive lung disease (RLD) and obstructive lung disease
      (OLD) risks in the general Chinese population. DESIGN: A cross-sectional
      investigation in the Wuhan cohort population. SETTING: A heavily polluted Chinese
      city. PARTICIPANTS: A total of 2460 community-living Chinese adults from the
      Wuhan cohort were included in our analysis. MAIN OUTCOME MEASURES: Spirometric
      parameters (FVC, forced vital capacity; FEV1, forced expiratory volumes in 1 s;
      FEV1/FVC ratio), RLD and OLD. RESULTS: The dose-response associations of
      pulmonary function, and RLD and OLD, with 23 urinary metals were assessed using
      regression analysis after adjusting for potential confounders. The false
      discovery rate (FDR) method was used to correct for multiple hypothesis tests.
      Our results indicated that there were positive dose-response associations of
      urinary iron with FEV1 and FEV1/FVC ratio, vanadium with FEV1, and copper and
      selenium with FEV1/FVC ratio, while a negative dose-response association was
      observed between urinary lead and FEV1/FVC ratio (all p<0.05). After additional
      adjusting for multiple comparisons, only iron was dose dependently related to
      FEV1/FVC ratio (FDR adjusted p<0.05). The dose-response association of iron and
      lead, with decreased and increased chronic obstructive pulmonary disease risk,
      respectively, was also observed (both p<0.05). Additionally, we found significant
      association of urinary zinc with RLD and interaction effects of smoking status
      with lead on FEV1/FVC, and with cadmium on FVC and FEV1. CONCLUSIONS: These
      results suggest that multiple urinary metals are associated with altered
      pulmonary function, and RLD and OLD prevalences.

PMID- 25998038
TI  - How different countries addressed the sudden growth of e-cigarettes in an online
      tobacco control community.
AB  - OBJECTIVE: The sudden growth of e-cigarettes over the last decade has forced
      advocates and critics scrambling to bolster support for their respective sides.
      Bridging the divide in geographic barriers, social networking sites were an ideal
      meeting place for international activist communities, affording them the ability
      to organise events and discuss new topics in real time. This study examines how e
      cigarettes are addressed in GLOBALink, an online international tobacco control
      community. We seek to discover if the pattern of activity in e-cigarette
      discussions changes over time. We are also interested in understanding the
      characteristics of sentiment toward e-cigarettes in discussion topics between
      countries with different network characteristics. DESIGN: Network analysis to
      explore the relationships between members from different countries, and sentiment
      analysis of messages and threads to identify patterns of how different countries
      address e-cigarette topics. SETTING: GLOBALink, an online international tobacco
      control community. PARTICIPANTS: Network analysis based on GLOBALink members from
      37 different countries. Sentiment analysis based on 853 posted messages, with
      over 1.4 million words. OUTCOME MEASURES: Network centrality measures in country
      interaction data, including degree, closeness and betweenness. Sentiment scores
      for each message, and differences between country scores. RESULTS: The network
      analysis found a core/periphery structure where central countries focused on
      active positive discussions pertaining to e-cigarettes, while isolated and
      peripheral countries posted negative topics without many responses. A qualitative
      examination of message topics suggests that general subjects elicit more
      interactions than those that are context specific. CONCLUSIONS: E-cigarettes are
      a polarising topic that can be seen in how countries appear to discuss related
      topics with others who share the same opinions. More work is needed to help
      communities stay informed of current research, and diffuse objective information.
      Network and sentiment analyses offer a strong combination of methodologies that
      can help support such efforts.

PMID- 25998040
TI  - Thermal aggregation of hen egg white proteins in the presence of salts.
AB  - Hen egg white contains more than 40 kinds of proteins with concentrations
      reaching 100 mg/mL. Highly concentrated protein mixtures are common in the food
      industry, but the effects of a crowded environment containing salts on protein
      stability and aggregation have only been investigated using pure protein
      solutions. Here, we investigated the thermal aggregation of hen egg white protein
      (EWP) at various concentrations in the presence of inorganic salts by solubility
      measurements and SDS-PAGE. EWP at 1 mg/mL formed aggregates with increasing
      temperature above 55  degrees C; the aggregation temperatures increased in the
      presence of inorganic salt with the Hofmeister series. Namely, the chaotrope 0.5
      M NaSCN completely suppressed the thermal aggregation of 1 mg/mL EWP. As the
      protein concentration increased, NaSCN unexpectedly enhanced the protein
      aggregation; the aggregation temperature of 10 and 100 mg/mL EWP solutions were
      dramatically decreased at 62 and 47  degrees C, respectively. This decrease in
      aggregation temperatures due to the chaotrope was described by the excluded
      volume effect, based on a comparative experiment using Ficoll 70 as a neutral
      crowder. By contrast, the kosmotrope Na2SO4 did not affect the aggregation
      temperature at concentrations from 1 to 100 mg/mL EWPs. The unexpected fact that
      a chaotrope rather enhanced the protein aggregation at high concentration
      provides new insight into the aggregation phenomena with the Hofmeister effect as
      well as the crude state of highly concentrated proteins.

PMID- 25998039
TI  - Relationship between low Ankle-Brachial Index and rapid renal function decline in
      patients with atrial fibrillation: a prospective multicentre cohort study.
AB  - OBJECTIVE: To investigate the relationship between Ankle-Brachial Index (ABI) and
      renal function progression in patients with atrial fibrillation (AF). DESIGN:
      Observational prospective multicentre cohort study. SETTING: Atherothrombosis
      Center of I Clinica Medica of 'Sapienza' University of Rome; Department of
      Medical and Surgical Sciences of University Magna Graecia of Catanzaro; Atrial
      Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment
      Collaborative Italian Study. PARTICIPANTS: 897 AF patients on treatment with
      vitamin K antagonists. MAIN OUTCOME MEASURES: The relationship between basal ABI
      and renal function progression, assessed by the estimated Glomerular Filtration
      Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of
      follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73
      m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end
      points, respectively. RESULTS: Mean age was 71.8+/-9.0 years and 41.8% were
      women. Low ABI (ie, <=0.90) was present in 194 (21.6%) patients. Baseline median
      eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR<60 mL/min/1.73
      m(2). Annual decline of eGFR was -2.0 (IQR -7.4/-0.4) mL/min/1.73 m(2)/year, and
      32.4% patients had a rapid decline in eGFR. Multivariable logistic regression
      analysis showed that ABI <=0.90 (OR 1.516 (95% CI 1.075 to 2.139), p=0.018) and
      arterial hypertension (OR 1.830 95% CI 1.113 to 3.009, p=0.017) predicted a rapid
      eGFR decline, with an inverse association for angiotensin converting enzyme (ACE)
      inhibitors/angiotensin receptor blockers (OR 0.662 95% CI 0.464 to 0.944,
      p=0.023). Among the 639 patients with AF with eGFR >60 mL/min/1.73 m(2), 153
      (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI <=0.90 was also an
      independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI
      1.205 to 2.845, p=0.005). CONCLUSIONS: In patients with AF, an ABI <=0.90 is
      independently associated with a rapid decline in renal function and incident
      eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at
      risk of renal function deterioration. TRIAL REGISTRATION NUMBER: NCT01161251.

PMID- 25998042
TI  - Population pharmacokinetics modeling and analysis of foretinib in adult patients
      with advanced solid tumors.
AB  - Foretinib is a multikinase inhibitor that inhibits multiple receptor tyrosine
      kinases, including MET and VEGFR, with the potential for treatment of solid
      tumors. Hepatocellular carcinoma (HCC) pathogenesis is associated with
      overexpression of MET, and physiologic changes in the livers of HCC patients may
      decrease CYP3A isozyme-mediated metabolism of foretinib. A population
      pharmacokinetic model of foretinib was developed to explore the effect of tumor
      type, formulation, and other covariates. Data from 1 HCC study in Asia and 3 non
      HCC studies in the United States with varying foretinib regimens and formulations
      were used for analysis. A 2-compartment model with a linear first-order
      absorption and elimination and lag time in absorption adequately described
      foretinib pharmacokinetics in 132 advanced non-HCC and HCC patients and
      identified an effect of formulations on bioavailability. The bisphosphate salt
      capsules and freebase tablets had a relative bioavailability 37% and 20% higher,
      respectively, than the solution formulation. HCC patients had ~19.6% lower mean
      clearance (70.14 L/h), ~16% lower mean volume of distribution (1725.6 L), and
      higher dose-normalized exposure compared with non-HCC patients. This could be a
      result of differences in metabolism in HCC patients, body weight, or activity of
      CYP3A isozymes between Asian and Western cancer patients. 

PMID- 25998041
TI  - Proteomic Analysis of Extracellular Vesicles Released by Adipocytes of Otsuka
      Long-Evans Tokushima Fatty (OLETF) Rats.
AB  - Extracellular vesicles (EVs) such as exosomes are secretory vesicles that act as
      autocrine, paracrine, or endocrine messengers; mediate intercellular cross-talk;
      and carry a cargo of various proteins. Because EVs can be transported to
      recipient cells via circulation, many researchers have been studying EVs from
      immune cells or cancer cells. Adipocytes are also considered endocrine cells and
      secrete adipokines such as adiponectin, regulating a variety of intracellular
      signaling pathways. Expansion of adipose tissue in obesity alters adipokine
      secretion, thereby increasing the risk of metabolic diseases. Characterization of
      adipocyte-derived exosomes is necessary to explain the communication between
      adipocytes and other cell types. In the present study, to identify proteins
      associated with adipocyte-derived exosomes, we isolated exosomes from adipose
      tissue of obese diabetic and obese nondiabetic rats. We identified proteins by
      analyzing exosomes from obese rats with type 2 diabetes and their matched control
      littermates using nano-liquid chromatography with tandem mass spectrometry
      coupled with label-free relative quantification. We identified 509 proteins from
      adipocytes including 81 known adipokines; ~78% of all the identified proteins
      were categorized as exosome-associated proteins. Among the protein profiles, we
      uncovered 128 upregulated and 72 downregulated proteins, which are differentially
      expressed in OLETF adipocyte-derived exosomes. This study seems to demonstrate
      for the first time hundreds of proteins in exosomes released by adipocytes in
      obese rats and rats with type 2 diabetes. Thus, protein profiles of exosomes from
      adipocytes possibly indicate the transmission of signals as part of cell-cell
      communication and should further our understanding of obesity- and diabetes
      related diseases.

PMID- 25998043
TI  - A Conversation with Cohn on the Activation of CD4 T Cells.
AB  - Despite an agreement on most issues surrounding models for how lymphocytes are
      activated and inactivated, and arising out of the 1970 Two Signal Model of
      lymphocyte activation, Cohn and I have different perspectives on two critical
      issues concerning the activation of CD4 T cells. One issue is the origin of the
      first effector T helper (eTh) cells, postulated by both of us to be required to
      optimally activate precursor Th (pTh), that is naive CD4 T cells, to further
      generate eTh cells. The second issue arises from our agreement that the antigen
      dependent CD4 T cell cooperation, that we both postulate is required to activate
      naive CD4 T (pTh) cells, most likely is mediated by the operational recognition
      of linked epitopes. Although agreeing on the centrality of this operational
      mechanism, we disagree about how it might be realized at the molecular/cellular
      level. I respond here to issues raised by Cohn concerning these two mechanistic
      questions, in his response to my recent article on the activation and
      inactivation of mature CD4 T cells. 

PMID- 25998044
TI  - Aetiological profile of women presenting with premature ovarian failure to a
      single tertiary care center in Oman.
AB  - BACKGROUND: Premature ovarian failure is estimated to affect at least 1%-3% of
      adult women. There are several aetio-pathogenic factors that may cause premature
      ovarian failure including iatrogenic causes, genetic, autoimmune, infectious and
      idiopathic. The aim of this study was to identify the aetiological profile of
      women with premature ovarian failure presenting to Sultan Qaboos University
      hospital. METHOD: A retrospective medical record review was conducted from June
      2006 to October 2012. All women diagnosed with symptoms and/or laboratory
      evidence of premature ovarian failure (follicle stimulating hormone >=40 UI/L and
      less than 40 years of age) were enrolled in this study. Possible causes of
      premature ovarian failure were obtained and classified into main aetiological
      factors. RESULTS: There were 90 patients during the study period, of which, 39
      (43%) were following chemotherapy and bone marrow transplant. The second most
      common reason was idiopathic (n = 29; 31%) followed by autoimmune diseases (n =
      8; 9%) and genetic disorders (n = 7; 8%). Most chemotherapy cases (69%) were
      among the young age group, while in the older age group idiopathic was the
      commonest (48%). CONCLUSION: Compared to the world literature, the most common
      cause of premature ovarian failure in this study was chemotherapy induced,
      especially in young girls undergoing bone marrow transplantation. This is due to
      high prevalence of transplantable hereditary haematological disorders like
      thalassemia and sickle-cell disease in this part of the world. Current standard
      of care recommends cryopreservation of ovarian tissue to preserve ovarian
      function in young girls undergoing bone marrow transplantation for such
      disorders.

PMID- 25998045
TI  - Genetic association and altered gene expression of osteoprotegerin in
      otosclerosis patients.
AB  - Otosclerosis (OTSC) is a late-onset hearing disorder characterized by increased
      bone turnover in the otic capsule. Disturbed osteoprotegerin expression has been
      found in the otosclerotic foci which may have an important role in the
      pathogenesis of OTSC. To identify the genetic risk factors, we sequenced the
      coding region and exon-intron boundaries of the OPG gene in 254 OTSC patients and
      262 controls. Sequence analysis identified five known polymorphisms c.9C>G,
      c.30+15C>T, c.400+4C>T, c.768A>G, and c.817+8A>C. Testing of these SNPs revealed
      sex specific association with c.9C>G in males and c.30+15C>T in females after
      multiple correction. Furthermore, meta-analysis provided evidence of association
      of the c.9C>G polymorphism with OTSC. In secondary analysis, we investigated the
      mRNA expression of OPG and associated genes RANK and RANKL in otosclerotic
      tissues compared to controls. Expression analysis revealed significantly
      missing/reduced OPG expression only in otosclerotic tissues. However, the signal
      sequence polymorphism c.9C>G has shown no effect on OPG mRNA expression. In
      conclusion, our results suggest that the risk of OTSC is influenced by variations
      in the OPG gene along with other factors which might regulate its altered
      expression in otosclerotic tissues. Further research is warranted to elucidate
      the mechanisms underlying these observations. 

PMID- 25998046
TI  - MicroRNA-377 predicts poor clinical outcome of gastric cancer and induces
      tumorigenesis by targeting multiple tumor-suppressor genes.
AB  - Gastric cancer (GC) is a major cause of cancer mortality worldwide. MicroRNAs are
      evolutionally conserved small non-coding RNAs that are critical for the
      regulation of gene expression. The aberrant expression of microRNA (miRNA) is
      involved in tumorigenesis and prognosis. In the present study, the clinical
      significance of miR-377 was assessed using RT-qPCR and MTT assay. The results
      showed that the expression of miR-377 was upregulated in GC compared with normal
      gastric tissues, and its expression level was increased in GC cell lines compared
      with normal gastric cells. In addition, there was a significant association
      between miR-377 expression and clinicopathological characteristics, in particular
      distant metastasis, TNM stage and early recurrence. GC patients with a higher miR
      377 expression showed significantly poorer overall survival (OR) and shorter time
      to recurrence than those with a lower miR-377 expression. The Cox regression
      analysis identified miR-377 overexpression as an independent prognostic factor
      for GC. Overexpression of miR-377 in MKN-45 GC cells significantly promoted cell
      proliferation, whereas the suppression of miR-377 inhibited these effects.
      Furthermore, miR-377 downregulated p53, PTEN and TIMP1 expression by directly
      targeting the 3'-untranslated region of these target genes. Collectively, miR-377
      potentially served as a new molecular predictive biomarker of GC tumorigenesis
      and prognosis, which may be useful in targeted therapy and the prognosis of GC
      patients.

PMID- 25998047
TI  - Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic
      Cathinone Derivatives.
AB  - Synthetic cathinones, often sold as "bath salts," are a popular class of
      recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine,
      and methylenedioxymethamphetamine. The increased prevalence and health
      consequences of synthetic cathinone use has prompted regulatory agencies to
      control a number of these compounds; however, a broad class of analogous
      compounds known as the second-generation cathinones has been brought to the
      market to take the place of the banned synthetic cathinone derivatives. The
      current study aims to characterize the behavioral pharmacology of three
      pyrrolidinylated second-generation cathinones: 4-methyl-alpha
      pyrrolidinopropiophenone (4'-MePPP), alpha-pyrrolidinopropiobutiophenone (alpha
      PBP), and alpha-pyrrolidinopentiophenone (alpha-PVP). Locomotor activity was
      tested in mice over an 8-hour period. The discriminative stimulus effects of
      these compounds were tested in rats trained to discriminate either cocaine or
      methamphetamine. The rewarding effects of these drugs were assessed in mice using
      conditioned place preference. Both alpha-PBP and alpha-PVP produced long-lasting
      increases in locomotor activity across a wide range of doses, whereas 4'-MePPP
      produced locomotor stimulation only at 30 mg/kg. Both alpha-PBP and alpha-PVP
      fully substituted for the discriminative stimulus effects of both cocaine and
      methamphetamine, whereas 4'-MePPP substituted fully for the discriminative
      stimulus effects of methamphetamine only. Both alpha-PBP and alpha-PVP produced
      conditioned place preference in an inverted U-shaped dose effect, whereas 4'
      MePPP did not produce conditioned place preference. These findings suggest that
      alpha-PBP and alpha-PVP are likely to be recreationally used and have potential
      for addiction and abuse, but 4'-MePPP may not. 

PMID- 25998048
TI  - Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol
      Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced
      Cannabimimetic Side Effects in Mice.
AB  - Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase
      (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids N
      arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces
      antinociception but with minimal cannabimimetic side effects. Although selective
      inhibitors of either enzyme often show partial efficacy in various nociceptive
      models, their combined blockade elicits augmented antinociceptive effects, but
      side effects emerge. Moreover, complete and prolonged MAGL blockade leads to
      cannabinoid receptor type 1 (CB1) receptor functional tolerance, which represents
      another challenge in this potential therapeutic strategy. Therefore, the present
      study tested whether full FAAH inhibition combined with partial MAGL inhibition
      would produce sustained antinociceptive effects with minimal cannabimimetic side
      effects. Accordingly, we tested a high dose of the FAAH inhibitor PF-3845 (N-3
      pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1
      piperidinecarboxamide; 10 mg/kg) given in combination with a low dose of the MAGL
      inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5
      yl(hydroxy)methyl)piperidine-1-carboxylate] (4 mg/kg) in mouse models of
      inflammatory and neuropathic pain. This combination of inhibitors elicited
      profound increases in brain AEA levels (>10-fold) but only 2- to 3-fold increases
      in brain 2-AG levels. This combination produced significantly greater
      antinociceptive effects than single enzyme inhibition and did not elicit common
      cannabimimetic effects (e.g., catalepsy, hypomotility, hypothermia, and
      substitution for Delta(9)-tetrahydrocannabinol in the drug-discrimination assay),
      although these side effects emerged with high-dose JZL184 (i.e., 100 mg/kg).
      Finally, repeated administration of this combination did not lead to tolerance to
      its antiallodynic actions in the carrageenan assay or CB1 receptor functional
      tolerance. Thus, full FAAH inhibition combined with partial MAGL inhibition
      reduces neuropathic and inflammatory pain states with minimal cannabimimetic
      effects. 

PMID- 25998049
TI  - Schwann Cells Metabolize Extracellular 2',3'-cAMP to 2'-AMP.
AB  - The 3',5'-cAMP-adenosine pathway (3',5'-cAMP->5'-AMP->adenosine) and the 2',3'
      cAMP-adenosine pathway (2',3'-cAMP->2'-AMP/3'-AMP->adenosine) are active in the
      brain. Oligodendrocytes participate in the brain 2',3'-cAMP-adenosine pathway via
      their robust expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase;
      converts 2',3'-cAMP to 2'-AMP). Because Schwann cells also express CNPase, it is
      conceivable that the 2',3'-cAMP-adenosine pathway exists in the peripheral
      nervous system. To test this and to compare the 2',3'-cAMP-adenosine pathway to
      the 3',5'-cAMP-adenosine pathway in Schwann cells, we examined the metabolism of
      2',3'-cAMP, 2'-AMP, 3'-AMP, 3',5'-cAMP, and 5'-AMP in primary rat Schwann cells
      in culture. Addition of 2',3'-cAMP (3, 10, and 30 uM) to Schwann cells increased
      levels of 2'-AMP in the medium from 0.006 +/- 0.002 to 21 +/- 2, 70 +/- 3, and
      187 +/- 10 nM/ug protein, respectively; in contrast, Schwann cells had little
      ability to convert 2',3'-cAMP to 3'-AMP or 3',5'-cAMP to either 3'-AMP or 5'-AMP.
      Although Schwann cells slightly converted 2',3'-cAMP and 2'-AMP to adenosine,
      they did so at very modest rates (e.g., 5- and 3-fold, respectively, more slowly
      compared with our previously reported studies in oligodendrocytes). Using
      transected myelinated rat sciatic nerves in culture medium, we observed a time
      related increase in endogenous intracellular 2',3'-cAMP and extracellular 2'-AMP.
      These findings indicate that Schwann cells do not have a robust 3',5'-cAMP
      adenosine pathway but do have a 2',3'-cAMP-adenosine pathway; however, because
      the pathway mostly involves 2'-AMP formation rather than 3'-AMP, and because the
      conversion of 2'-AMP to adenosine is slow, metabolism of 2',3'-cAMP mostly
      results in the accumulation of 2'-AMP. Accumulation of 2'-AMP in peripheral
      nerves postinjury could have pathophysiological consequences. 

PMID- 25998050
TI  - Specific accumulation of orally administered redox nanotherapeutics in the
      inflamed colon reducing inflammation with dose-response efficacy.
AB  - Although current medications for ulcerative colitis (UC) are effective to some
      extent, there are still some limitation of their use due to the non-specific
      distribution, drug metabolism in the gastrointestinal tract, and severe adverse
      effects. In our previous studies, we developed oral redox nanoparticles (RNP(O))
      that specifically accumulated and scavenged overproduced reactive oxygen species
      (ROS) in an inflamed colon. However, the mechanism leading to specific
      accumulation of RNP(O) in an inflamed colon is still unclear. In this study, we
      investigated the cellular uptake of RNP(O) into ROS-treated epithelial colonic
      cells in vitro, and compared to the untreated cells, found a significantly
      increased uptake in ROS-treated cells. In vivo, we discovered that orally
      administered RNP(O) were not internalized into the cells of a normal colon. A
      significant amount of disintegrated RNP(O) was detected in the cells of an
      inflamed colon of dextran sodium sulfate (DSS)-induced colitis mice, resulting in
      scavenging of ROS and suppression of inflammation with low adverse effects.
      Furthermore, we confirmed a significant reduction of disease activity and a
      robust dose response efficacy following RNP(O) treatment in acute DSS-induced
      colitis mice, outperforming the positive control 5-aminosalicylic acid. Oral
      administration of RNP(O) is a promising approach to develop a new therapy for UC
      disease. 

PMID- 25998051
TI  - Selective delivery of therapeutic single strand antimiRs by aptamer-based
      conjugates.
AB  - Development of RNA-based antagonists (antimiRs) for disease-associated miRNAs in
      specific cell types or tissues has recently become a promising approach for
      treating several pathological conditions, including cancer. In order to explore
      the use of RNA-aptamers as carriers for cell-targeted delivery of antimiRs, here
      we designed two different conjugates using as carrier two aptamers that bind and
      antagonize cancer-associated receptor tyrosine kinases, Axl and PDGFRbeta. We
      conjugated the tumor suppressor antimiR-222 to each aptamer demonstrating: 1)
      effective and selective delivery to receptor-expressing tumor cells, 2) increased
      expression of miR-222 target mRNAs, and 3) functional synergy between the kinase
      inhibitory aptamer and the antimiR antagonizing functions. Furthermore, we
      generated modular molecules in which two different antimiR sequences connected in
      tandem are conjugated to a unique carrier aptamer. We proved this strategy to be
      effective to deplete multiple microRNAs simultaneously, thus combining the
      effects of different antimiRs without losing the cell targeting specificity. 

PMID- 25998053
TI  - Salivary microbiota-immune profiling in cirrhosis: could this be the noninvasive
      strategy that will revolutionize prognostication in hepatology?

PMID- 25998052
TI  - Cetuximab-oxaliplatin-liposomes for epidermal growth factor receptor targeted
      chemotherapy of colorectal cancer.
AB  - Oxaliplatin (L-OH), a platinum derivative with good tolerability is currently
      combined with Cetuximab (CTX), a monoclonal antibody (mAb), for the treatment of
      certain (wild-type KRAS) metastatic colorectal cancer (CRC) expressing epidermal
      growth factor receptor (EGFR). Improvement of L-OH pharmacokinetics (PK) can be
      provided by its encapsulation into liposomes, allowing a more selective
      accumulation and delivery to the tumor. Here, we aim to associate both agents in
      a novel liposomal targeted therapy by linking CTX to the drug-loaded liposomes.
      These EGFR-targeted liposomes potentially combine the therapeutic activity and
      selectivity of CTX with tumor-cell delivery of L-OH in a single therapeutic
      approach. L-OH liposomes carrying whole CTX or CTX-Fab' fragments on their
      surface were designed and characterized. Their functionality was tested in vitro
      using four human CRC cell lines, expressing different levels of EGFR to
      investigate the role of CTX-EGFR interactions in the cellular binding and uptake
      of the nanocarriers and encapsulated drug. Next, those formulations were
      evaluated in vivo in a colorectal cancer xenograft model with regard to tumor
      drug accumulation, toxicity and therapeutic activity. In EGFR-overexpressing cell
      lines, intracellular drug delivery by targeted liposomes increased with receptor
      density reaching up to 3-fold higher levels than with non-targeted liposomes.
      Receptor specific uptake was demonstrated by competition with free CTX, which
      reduced internalization to levels similar to non-targeted liposomes. In a CRC
      xenograft model, drug delivery was strongly enhanced upon treatment with targeted
      formulations. Liposomes conjugated with monovalent CTX-Fab' fragments showed
      superior drug accumulation in tumor tissue (2916.0+/-507.84ng/g) compared to CTX
      liposomes (1546.02+/-362.41ng/g) or non-targeted liposomes (891.06+/-155.1ng/g).
      Concomitantly, CTX-Fab' targeted L-OH liposomes outperformed CTX-liposomes, which
      on its turn was still more efficacious than non-targeted liposomes and free drug
      treatment in CRC bearing mice. These results show that site-directed conjugation
      of monovalent CTX-Fab' provides targeted L-OH liposomes that display an increased
      tumor drug delivery and efficacy over a formulation with CTX and non-targeted
      liposomes. 

PMID- 25998056
TI  - Personal reflections on the communication skills during clinical clerkships. A
      challenge for students and professors: Not only for oncology's courses.

PMID- 25998055
TI  - Registered report: Coadministration of a tumor-penetrating peptide enhances the
      efficacy of cancer drugs.
AB  - The Science in 2010 (Sugahara et al., 2010). The key experiments being replicated
      include Figure 2 and Supplemental Figure 9A. In Figure 2, Sugahara and colleagues
      presented data on the tumor penetrance of doxorubicin (DOX) when co-administered
      with the peptide iRGD, as well as the effect of co-treatment of DOX and iRGD on
      tumor weight and cell death. In Supplemental Figure 9A, they tracked body weight
      of mice treated with DOX and iRGD to provide evidence that iRGD does not increase
      known DOX toxicity. The Reproducibility Project: Cancer Biology is a
      collaboration between the eLife. 

PMID- 25998054
TI  - The kinase DYRK1A reciprocally regulates the differentiation of Th17 and
      regulatory T cells.
AB  - The balance between Th17 and T regulatory (Treg) cells critically modulates
      immune homeostasis, with an inadequate Treg response contributing to inflammatory
      disease. Using an unbiased chemical biology approach, we identified a novel role
      for the dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A in
      regulating this balance. Inhibition of DYRK1A enhances Treg differentiation and
      impairs Th17 differentiation without affecting known pathways of Treg/Th17
      differentiation. Thus, DYRK1A represents a novel mechanistic node at the branch
      point between commitment to either Treg or Th17 lineages. Importantly, both Treg
      cells generated using the DYRK1A inhibitor harmine and direct administration of
      harmine itself potently attenuate inflammation in multiple experimental models of
      systemic autoimmunity and mucosal inflammation. Our results identify DYRK1A as a
      physiologically relevant regulator of Treg cell differentiation and suggest a
      broader role for other DYRK family members in immune homeostasis. These results
      are discussed in the context of human diseases associated with dysregulated DYRK
      activity. 

PMID- 25998058
TI  - Insights into the life history and ecology of a large shortfin mako shark Isurus
      oxyrinchus captured in southern California.
AB  - In June 2013, a record-breaking female Isurus oxyrinchus (total length 373 cm,
      mass 600 kg) was captured by rod and reel off Huntington Beach, California, where
      it was subsequently donated to research and provided a rare opportunity to
      collect the first data for a female I. oxyrinchus of this size. Counts of
      vertebral band pairs estimate the shark to have been c. 22 years old, depending
      upon assumptions of band-pair deposition rates, and the distended uteri and spent
      ovaries indicated that this shark had recently given birth. The stomach contained
      a c. 4 year-old female California sea lion Zalophus californianus that confirmed
      the high trophic position of this large I. oxyrinchus, which was corroborated
      with the high levels of measured contaminants and tissue isotope analyses. 

PMID- 25998060
TI  - Spontaneously Breathing Preterm Infants Change in Tidal Volume to Improve Lung
      Aeration Immediately after Birth.
AB  - OBJECTIVE: To examine the temporal course of lung aeration at birth in preterm
      infants <33 weeks gestation. STUDY DESIGN: The research team attended deliveries
      of preterm infants <33 weeks gestation at the Royal Alexandra Hospital. Infants
      who received only continuous positive airway pressure were eligible for
      inclusion. A combined carbon dioxide (CO2) and flow-sensor was placed between the
      mask and the ventilation device. To analyze lung aeration patterns during
      spontaneous breathing, tidal volume (VT), and exhaled CO2 (ECO2) were recorded
      for the first 100 breaths. RESULTS: Thirty preterm infants were included with a
      total of 1512 breaths with mask leak <30%. Mean (SD) gestational age and birth
      weight was 30 (1) weeks and 1478 (430) g. Initial VT and ECO2 for the first 30
      breaths was 5-6 mL/kg and 15-22 mm Hg, respectively. VT and ECO2 increased over
      the next 20 breaths to 7-8 mL/kg and 25-32 mm Hg, respectively. For the remaining
      observation period VT decreased to 4-6 mL/kg and ECO2 continued to increase to 35
      37 mm Hg. CONCLUSIONS: Preterm infants begin taking deeper breaths approximately
      30 breaths after initiating spontaneous breathing to inflate their lungs.
      Concurrent CO2 removal rises as alveoli are recruited. Lung aeration occurs in 2
      phases: initially, large volume breaths with poor alveolar aeration followed by
      smaller breaths with elimination of CO2 as a consequence of adequate aeration.

PMID- 25998059
TI  - Human inversions and their functional consequences.
AB  - Polymorphic inversions are a type of structural variants that are difficult to
      analyze owing to their balanced nature and the location of breakpoints within
      complex repeated regions. So far, only a handful of inversions have been studied
      in detail in humans and current knowledge about their possible functional effects
      is still limited. However, inversions have been related to phenotypic changes and
      adaptation in multiple species. In this review, we summarize the evidences of the
      functional impact of inversions in the human genome. First, given that inversions
      have been shown to inhibit recombination in heterokaryotes, chromosomes
      displaying different orientation are expected to evolve independently and this
      may lead to distinct gene-expression patterns. Second, inversions have a role as
      disease-causing mutations both by directly affecting gene structure or regulation
      in different ways, and by predisposing to other secondary arrangements in the
      offspring of inversion carriers. Finally, several inversions show signals of
      being selected during human evolution. These findings illustrate the potential of
      inversions to have phenotypic consequences also in humans and emphasize the
      importance of their inclusion in genome-wide association studies. 

PMID- 25998061
TI  - Acoustic Analysis of Madhya and Taar Saptak/Sthayi in Indian Classical Singers.
AB  - OBJECTIVES: We aimed to compare the acoustic parameters of voice between Madhya
      Saptak/Sthayi (MS) and Taar Saptak/Sthayi (TS) in trained Indian classical
      singers and between males and females. PARTICIPANTS AND METHOD: Sixty-five adult
      trained Indian classical singers were instructed to produce MS and TS; the
      acoustic parameters were analyzed with the Multidimensional Voice Program.
      Descriptive statistics were used for analysis across tasks and gender. Two-way
      random-effects ANOVA was used to test the effect of gender and task. RESULTS:
      Male participants had a restricted range of fundamental frequency (F0),
      especially at high pitches. The acoustic analysis showed a statistically
      significant difference for F0 measures, range of F0, jitter and pitch
      perturbation quotient between males and females during MS and TS. CONCLUSION: The
      use of TS, that is, high-pitch phonation, during the clinical evaluation of
      singers enables an understanding of their vocal behavior in the higher scales of
      singing.

PMID- 25998062
TI  - Is safe surgery possible when resources are scarce?
AB  - The greatest burden of surgical disease exists in low- and middle-income
      countries, where the quality and safety of surgical treatment cause major
      challenges. Securing necessary and appropriate medical supplies and
      infrastructure remains a significant and under-recognised limitation to providing
      safe and high-quality surgical care in these settings. The majority of surgical
      instruments are sold in high-income countries. Limited market pressures lead to
      superfluous designs and inflated costs for these devices. This context creates an
      opportunity for frugal innovation-the search for designs that will enable low
      cost care without compromising quality. Although progressive examples of frugal
      surgical innovations exist, policy innovation is required to augment design
      pathways while fostering appropriate safety controls for prospective devices.
      Many low-cost, high-quality medical technologies will increase access to safe
      surgical care in low-income countries and have widespread applicability as all
      countries look to reduce the cost of providing care, without compromising
      quality. 

PMID- 25998064
TI  - Cognitive impairment is a negative short-term and long-term prognostic factor in
      elderly patients with hip fracture.
AB  - BACKGROUND: Subjects with severe cognitive impairment (CI) have a high-risk of
      hip fractures with increased rate of adverse postoperative functional outcomes
      and mortality. AIM: To evaluate the impact of different degrees of CI on
      functional recovery and mortality after hip fracture. DESIGN: Prospective
      observational study. SETTING: Two orthopedic surgery units. POPULATION: Two
      hundred twenty-eight consecutive patients after a hip surgery. METHODS: Patients
      were assessed at baseline through the Short Portable Mental Status Questionnaire
      (SPMSQ), an instrument that allows to categorize subjects as follows: cognitively
      intact (SPMSQ>=8) or with mild (SPMSQ=6-7), moderate (SPMSQ=3-5) and severe CI
      (SPMSQ<3). Barthel Index (BI) was used to assess functional disability. All
      patients underwent rehabilitation from the day after surgery to discharge (mean
      length of stay =10.2+/-3.4). Outcome measures were: (1) overall mortality up to
      12 months after surgery; (2) motor ability achieved at discharge from the
      orthopedic ward (sitting, standing, walking); (3) BI and SPMSQ at 1, 3, 6 and 12
      months postoperatively. RESULTS: All degrees of severity of CI were inversely
      correlated to the ability to walk at hospital discharge. At one year from
      surgery, the majority of patients with CI were functionally severely dependent,
      whereas about half of the cognitively intact ones gained a functional
      independence status. CI and the level of premorbid disability influenced the risk
      of death. CONCLUSION: CI for all degrees of severity is a negative prognostic
      factor in elderly patients with hip fracture. CLINICAL REHABILITATION IMPACT: We
      suggest evaluating the cognitive status of patients with hip fracture as it
      affects both the short and long-term functional recovery at any degree of
      severity.

PMID- 25998065
TI  - A Functional Variant at the miR-214 Binding Site in the
      Methylenetetrahydrofolatereductase Gene Alters Susceptibility to Gastric Cancer
      in a Chinese Han Population.
AB  - BACKGROUND AND AIMS: Single nucleotide polymorphisms in miRNA binding sites,
      which are located in mRNA 3' untranslated regions (3'-UTRs), were recently found
      to influence microRNA-target interactions. Specifically, such polymorphisms can
      modulatebinding affinity or create or destroy miRNA-binding sites; such variants
      have also been found to be associated with cancer risk. In this study, we
      explored the effect of a functional variant at the miR-214 binding site in the
      methylenetetrahydrofolate reductase gene (rs114673809) on gastric cancer (GC)
      risk in a hospital-based case-control study in a Chinese Han population. METHODS
      AND RESULTS: We genotyped the rs114673809 polymorphism in 345 gastric cancer
      patients and 376 cancer-free controls using the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) technique. The functions of
      rs114673809 were investigated using a luciferase activity assay and validated by
      immunoblotting. We found that participants carrying the rs114673809 AA genotype
      or A allele had a significantly increased risk of gastric cancer (OR = 1.667, 95%
      CI = 1.044-2.660, P = 0.034; OR = 1.261, 95% CI = 1.017-1.563, P = 0.037,
      respectively) compared to those carrying the GG genotype and G allele. In
      addition, rs114673809 modified the binding of hsa-miR-214 to MTHFR as well as
      MTHFR protein levels in gastric cancer patients. CONCLUSION: Our data suggested
      that rs114673809, which is located at the miR-214 binding site in the 3'-UTR of
      MTHFR, may play an important role in the development of gastric cancer in a
      Chinese Han population.

PMID- 25998063
TI  - State of the field: An informatics-based systematic review of the SOD1-G93A
      amyotrophic lateral sclerosis transgenic mouse model.
AB  - Numerous sub-cellular through system-level disturbances have been identified in
      over 1300 articles examining the superoxide dismutase-1 guanine 93 to alanine
      (SOD1-G93A) transgenic mouse amyotrophic lateral sclerosis (ALS) pathophysiology.
      Manual assessment of such a broad literature base is daunting. We performed a
      comprehensive informatics-based systematic review or 'field analysis' to
      agnostically compute and map the current state of the field. Text mining of
      recaptured articles was used to quantify published data topic breadth and
      frequency. We constructed a nine-category pathophysiological function-based
      ontology to systematically organize and quantify the field's primary data.
      Results demonstrated that the distribution of primary research belonging to each
      category is: systemic measures an motor function, 59%; inflammation, 46%;
      cellular energetics, 37%; proteomics, 31%; neural excitability, 22%; apoptosis,
      20%; oxidative stress, 18%; aberrant cellular chemistry, 14%; axonal transport,
      10%. We constructed a SOD1-G93A field map that visually illustrates and
      categorizes the 85% most frequently assessed sub-topics. Finally, we present the
      literature-cited significance of frequently published terms and uncover thinly
      investigated areas. In conclusion, most articles individually examine at least
      two categories, which is indicative of the numerous underlying pathophysiological
      interrelationships. An essential future path is examination of cross-category
      pathophysiological interrelationships and their co-correspondence to homeostatic
      regulation and disease progression. 

PMID- 25998067
TI  - Pelvic-floor-muscle-training adherence "modifiers": A review of primary
      qualitative studies-2011 ICS State-of-the-Science Seminar research paper III of
      IV.
AB  - AIMS: This review aims to locate and summarize the findings of qualitative
      studies exploring the experience of and adherence to pelvic floor muscle training
      (PFMT) to recommend future directions for practice and research. METHODS: Primary
      qualitative studies were identified through a conventional subject search of
      electronic databases, reference-list checking, and expert contact. A core
      eligibility criterion was the inclusion of verbatim quotes from participants
      about PFMT experiences. Details of study aims, methods, and participants were
      extracted and tabulated. Data were inductively grouped into categories describing
      "modifiers" of adherence (verified by a second author) and systematically
      displayed with supporting illustrative quotes. RESULTS: Thirteen studies (14
      study reports) were included; eight recruited only or predominantly women with
      urinary incontinence, three recruited postnatal women, and two included women
      with pelvic organ prolapse. The quality of methodological reporting varied. Six
      "modifiers" of adherence were described: knowledge; physical skill; feelings
      about PFMT; cognitive analysis, planning, and attention; prioritization; and
      service provision. CONCLUSIONS: Individuals' experience substantial difficulties
      with capability (particularly knowledge and skills), motivation (especially
      associated with the considerable cognitive demands of PFMT), and opportunity (as
      external factors generate competing priorities) when adopting and maintaining a
      PFMT program. Expert consensus was that judicious selection and deliberate
      application of appropriate behavior change strategies directed to the "modifiers"
      of adherence identified in the review may improve PFMT outcomes. Future research
      is needed to explore whether the review findings are congruent with the PFMT
      experiences of antenatal women, men, and adults with fecal incontinence.

PMID- 25998066
TI  - Identification of genomic regions involved in tolerance to drought stress and
      drought stress induced leaf senescence in juvenile barley.
AB  - BACKGROUND: Premature leaf senescence induced by external stress conditions, e.g.
      drought stress, is a main factor for yield losses in barley. Research in drought
      stress tolerance has become more important as due to climate change the number of
      drought periods will increase and tolerance to drought stress has become a goal
      of high interest in barley breeding. Therefore, the aim is to identify
      quantitative trait loci (QTL) involved in drought stress induced leaf senescence
      and drought stress tolerance in early developmental stages of barley (Hordeum
      vulgare L.) by applying genome wide association studies (GWAS) on a set of 156
      winter barley genotypes. RESULTS: After a four weeks stress period (BBCH 33) leaf
      colour as an indicator of leaf senescence, electron transport rate at photosystem
      II, content of free proline, content of soluble sugars, osmolality and the
      aboveground biomass indicative for drought stress response were determined in the
      control and stress variant in greenhouse pot experiments. Significant phenotypic
      variation was observed for all traits analysed. Heritabilities ranged between
      0.27 for osmolality and 0.61 for leaf colour in stress treatment and significant
      effects of genotype, treatment and genotype x treatment were estimated for most
      traits analysed. Based on these phenotypic data and 3,212 polymorphic single
      nucleotide polymorphisms (SNP) with a minor allele frequency >5% derived from the
      Illumina 9 k iSelect SNP Chip, 181 QTL were detected for all traits analysed.
      Major QTLs for drought stress and leaf senescence were located on chromosome 5H
      and 2H. BlastX search for associated marker sequences revealed that respective
      SNPs are in some cases located in proteins related to drought stress or leaf
      senescence, e.g. nucleotide pyrophosphatase (AVP1) or serine/ threonin protein
      kinase (SAPK9). CONCLUSIONS: GWAS resulted in the identification of many QTLs
      involved in drought stress and leaf senescence of which two major QTLs for
      drought stress and leaf senescence were located on chromosome 5H and 2H. Results
      may be the basis to incorporate breeding for tolerance to drought stress or leaf
      senescence in barley breeding via marker based selection procedures.

PMID- 25998068
TI  - Wall Thickness, Pulmonary Hypertension, and Diastolic Filling Abnormalities
      Predict Response to Postoperative Biventricular Pacing.
AB  - OBJECTIVE: Post-cardiopulmonary bypass biventricular pacing improves hemodynamics
      but without clearly defined predictors of response. Based on preclinical studies
      and prior observations, it was suspected that diastolic dysfunction or pulmonary
      hypertension is predictive of hemodynamic benefit. DESIGN: Randomized controlled
      study of temporary biventricular pacing after cardiopulmonary bypass. SETTING:
      Single-center study at university-affiliated tertiary care hospital.
      INTERVENTIONS: Patients who underwent bypass with preoperative ejection fraction
      <=40% and QRS duration >=100 ms or double-valve surgery were enrolled. At 3 time
      points between separation from bypass and postoperative day 1, pacing delays were
      varied to optimize hemodynamics. PARTICIPANTS: Data from 43 patients were
      analyzed. MEASUREMENTS AND MAIN RESULTS: Cardiac output and arterial pressure
      were measured under no pacing, atrial pacing, and biventricular pacing.
      Preoperative echocardiograms and pulmonary artery catheterizations were reviewed,
      and measures of both systolic and diastolic function were compared to hemodynamic
      response. Early after separation, improvement in cardiac output was positively
      correlated with pulmonary vascular resistance (R(2) = 0.97, p<0.001), ventricle
      wall thickness (R(2) = 0.72, p = 0.002)), and E/e', a measure of abnormal
      diastolic ventricular filling velocity (R(2) = 0.56, p = 0.04). Similar trends
      were seen with mean arterial pressure. QRS duration and ejection fraction did not
      correlate significantly with improvements in hemodynamics. CONCLUSIONS: There may
      be an effect of biventricular pacing related to amelioration of abnormal
      diastolic filling patterns rather than electrical resynchronization in the
      postoperative state.

PMID- 25998069
TI  - The Optimal Angle of Head Rotation for Internal Jugular Cannulation as Determined
      by Ultrasound Evaluation.
AB  - OBJECTIVES: The aim of this study was to determine the degree of head rotation
      that creates the maximal anatomic separation between the right internal jugular
      vein and the carotid artery. DESIGN: Single-center prospective, observational
      cohort study. SETTING: University medical center. PARTICIPANTS: Fifty patients
      aged>21 years and undergoing cardiac surgery. INTERVENTIONS: An ultrasound
      machine equipped with a digital caliper was used to determine the relational
      anatomy of the internal jugular vein and the carotid artery, with patients in the
      Trendelenburg position at head angles of -15 degrees , 0 degrees ,+15 degrees
      ,+30 degrees ,+45 degrees ,+60 degrees ,+75 degrees , and+90 degrees .
      MEASUREMENTS AND MAIN RESULTS: When examining the percentage of the internal
      jugular vein vertical diameter that is not overlapped by the carotid artery
      (vertically unencumbered), there was a difference between the head angle groups
      (p<0.01). Unencumbered vertical distance was different between+75 degrees  versus
      0 degrees , and+75 degrees  versus+15 degrees . At+75 degrees , 60.3%+/-5.3% of
      the internal jugular vein was unencumbered vertically, whereas at 0 degrees , it
      was 37.2%+/-3.9%, and at+15 degrees  it was 40.3%+/-3.8%. Only 72% of the
      patients were able to position their head at+75 degrees , and 54% of the subjects
      were able to position their head at+90 degrees . CONCLUSION: The authors found
      the internal jugular vein becomes more vertically separated from the carotid
      artery at more extreme angles of contralateral head rotation.

PMID- 25998070
TI  - Pterostilbene improves glycaemic control in rats fed an obesogenic diet:
      involvement of skeletal muscle and liver.
AB  - This study aims to determine whether pterostilbene improves glycaemic control in
      rats showing insulin resistance induced by an obesogenic diet. Rats were divided
      into 3 groups: the control group and two groups treated with either 15 mg kg(-1)
      d(-1) (PT15) or 30 mg kg(-1) d(-1) of pterostilbene (PT30). HOMA-IR was decreased
      in both pterostilbene-treated groups, but this reduction was greater in the PT15
      group (-45% and -22% respectively vs. the control group). The improvement of
      glycaemic control was not due to a delipidating effect of pterostilbene on
      skeletal muscle. In contrast, GLUT4 protein expression was increased (+58% and
      +52% vs. the control group), suggesting an improved glucose uptake. The
      phosphorylated-Akt/total Akt ratio was significantly enhanced in the PT30 group
      (+25%), and therefore a more efficient translocation of GLUT4 is likely.
      Additionally, in this group the amount of cardiotrophin-1 was significantly
      increased (+65%). These data suggest that the effect of pterostilbene on Akt is
      mediated by this cytokine. In the liver, glucokinase activity was significantly
      increased only in the PT15 group (+34%), and no changes were observed in glucose
      6-phosphatase activity. The beneficial effect of pterostilbene on glycaemic
      control was more evident with the lower dose, probably because in the PT15 group
      both the muscle and the liver were contributing to this effect, but in the PT30
      group only the skeletal muscle was responsible. In conclusion, pterostilbene
      improves glycaemic control in rats showing insulin resistance induced by an
      obesogenic diet. An increase in hepatic glucokinase activity, as well as in
      skeletal muscle glucose uptake, seems to be involved in the anti-diabetic effect
      of this phenolic compound.

PMID- 25998072
TI  - Role of Microglia in Autism: Recent Advances.
AB  - The neurobiological basis for autism remains poorly understood. However, the
      neuroinflammation processes play an important role in the induction of autistic
      behavioral changes. Microglial cells can exhibit widely differing functions
      during brain development, including synaptogenesis and stem cell proliferation,
      in addition to playing a role in the innate immunity. Mounting evidence indicates
      that microglial activation or dysfunction can profoundly affect neural
      development, resulting in neurodevelopmental disorders, including autism. These
      mechanisms in autism have been investigated using neuropathological studies of
      human autopsy brains, a large number of murine experimental models and in vivo
      neuroimaging studies of the human brain. The purpose of this review is to discuss
      microglial activation or dysfunction and to highlight the detrimental role that
      microglia play in the development of autism. The recent advances presented in
      this review support that further elucidation of the mechanisms and kinetics of
      microglial responses will help to establish a window for therapeutic intervention
      in individuals with autism.

PMID- 25998071
TI  - Analysis of stereotactic radiation vs. wedge resection vs. wedge resection plus
      Cesium-131 brachytherapy in early stage lung cancer.
AB  - PURPOSE: The purpose of the study was to evaluate the outcomes for wedge
      resection (WR), WR plus brachytherapy (WRB), or stereotactic body radiation
      therapy (SBRT) for early stage non-small lung cancer. METHODS AND MATERIALS:
      Retrospectively collected data of patients treated with WR, WRB, or SBRT (1993
      2012). Cesium-131 (Cs131) used in WRB group in patients with close or positive
      margins based on surgical assessment. Kaplan-Meier survival analysis, log-rank
      test used to compare disease-free survival/overall survival between different
      groups. Multivariable analysis, using Cox proportional hazards regression
      analysis, was performed to evaluate the independent effect of age, gender, and
      treatment procedure on disease-free survival. RESULTS: A total of 272 patients
      were included in the study (123 WR, 52 WR+Cs-131, 97 SBRT). Cs-131 was used with
      WRs that the surgeons deemed high risk. Local control (LC) was similar in the
      three groups and was achieved in 92.2% for WR group vs. 96.2% for WR+Cs-131 and
      95.5% for SBRT (p = 0.60). On multivariate analysis, although females showed a
      higher LC, neither LC nor distant metastasis were associated with age or gender
      (p = 0.65 and p = 0.41, respectively). Five-year overall survival was 100% in the
      WR+B group, 97.7% in the WR group, and 89.6% in the SBRT group (p = 0.02).
      Toxicity was similar in the three groups. CONCLUSION: WR, WR+ Cs-131, or SBRT are
      all excellent treatment options for patients with early stage non-small cell lung
      cancer that are not candidates for lobectomy. For high risk WRs, we favor use of
      Cesim-131 brachytherapy. Until a prospective randomized comparative study is done
      to evaluate the best treatment approach for early stage NSCLC, treatment
      selection should be based on a multidisciplinary team approach.

PMID- 25998073
TI  - Cardiovascular Causes of Pediatric Airway Compression: A Pictorial Review.
AB  - Airways compression by vascular structures is one of the important comorbidities
      of congenital heart disease with incidence of approximately 1%-2% in children.
      Airways compression is a consequence of abnormal configuration of the great
      vessels producing a vascular ring with enlargement of normal structures
      (pulmonary arteries or cardiac chambers) or because of surgery. A high index of
      suspicion for vascular airway compression is important in children with recurrent
      respiratory complaints. Early diagnosis and management are essential, as chronic
      airway compression causes significant morbidity. As the underlying anatomical
      patterns tend to be highly complex, presurgical imaging assessment is essential.

PMID- 25998076
TI  - Invited commentary.

PMID- 25998077
TI  - Invited commentary.

PMID- 25998078
TI  - Invited commentary.

PMID- 25998079
TI  - Invited commentary.

PMID- 25998080
TI  - Invited commentary.

PMID- 25998081
TI  - Invited commentary.

PMID- 25998082
TI  - Invited commentary.

PMID- 25998083
TI  - Unconscious Race and Class Biases among Registered Nurses: Vignette-Based Study
      Using Implicit Association Testing.
AB  - BACKGROUND: Implicit bias is an unconscious preference for a specific social
      group that can have adverse consequences for patient care. Acute care clinical
      vignettes were used to examine whether implicit race or class biases among
      registered nurses (RNs) impacted patient-management decisions. STUDY DESIGN: In a
      prospective study conducted among surgical RNs at the Johns Hopkins Hospital,
      participants were presented 8 multi-stage clinical vignettes in which patients'
      race or social class were randomly altered. Registered nurses were administered
      implicit association tests (IATs) for social class and race. Ordered logistic
      regression was then used to examine associations among treatment differences,
      race, or social class, and RN's IAT scores. Spearman's rank coefficients
      comparing RN's implicit (IAT) and explicit (stated) preferences were also
      investigated. RESULTS: Two hundred and forty-five RNs participated. The majority
      were female (n=217 [88.5%]) and white (n=203 [82.9%]). Most reported that they
      had no explicit race or class preferences (n=174 [71.0%] and n=108 [44.1%],
      respectively). However, only 36 nurses (14.7%) demonstrated no implicit race
      preference as measured by race IAT, and only 16 nurses (6.53%) displayed no
      implicit class preference on the class IAT. Implicit association tests scores did
      not statistically correlate with vignette-based clinical decision making.
      Spearman's rank coefficients comparing implicit (IAT) and explicit preferences
      also demonstrated no statistically significant correlation (r=-0.06; p=0.340 and
      r=-0.06; p=0.342, respectively). CONCLUSIONS: The majority of RNs displayed
      implicit preferences toward white race and upper social class patients on IAT
      assessment. However, unlike published data on physicians, implicit biases among
      RNs did not correlate with clinical decision making.

PMID- 25998084
TI  - Survey of the American College of Surgeons scholarship recipients: a story of
      generating academic leaders.
AB  - BACKGROUND: The objective of this survey was to provide a review of the American
      College of Surgeons (ACS) scholarship activity. STUDY DESIGN: The domestic ACS
      scholarship recipient survey was electronically transmitted twice to awardees
      from 1987 to 2007 (n=253). Themes of the survey included type of practice,
      activities during scholarship period, success of peer review funding, and the
      role of mentors. All survey responses were evaluated using SPSS version 20.
      RESULTS: There were 123 total responses, with 108 separate respondents (94, 1
      award; 13, 2 awards; 1, 3 awards). The group averaged 11.8 years in clinical
      practice, with the majority (90.2%) having an academic appointment. Seventy-seven
      percent of respondents were on a tenure track, and almost three-quarters (72.4%)
      of the respondents hold a major leadership position. In terms of research, 67.5%
      of respondents have received extramural funding; 10.6% have received patents. The
      average number of publications related to their funded research is 19.2 (range 0
      to 180). Most respondents perform peer review of research (73.2%), learned about
      the peer review process during their funding period (82.1%), and mentor medical
      students (88.6%). The average number of students currently mentored is 6.4; the
      average total trainees mentored is 13. Despite the significant research
      responsibilities of respondents, they still spend more time performing clinical
      care (49.2%) than research (30.4%). CONCLUSIONS: The ACS scholarship has a
      significant impact on the recipient's academic career, even in the setting of
      increasing clinical burdens. This program also appears to tangentially identify
      surgeons who become leaders in academic surgery.

PMID- 25998085
TI  - Implementing a standardized safe surgery program reduces serious reportable
      events: in reply to Nathanson and Bloomstone.

PMID- 25998086
TI  - Checking out the checklist.

PMID- 25998088
TI  - Tracing Dissectable Layers of Mesenteries Overcomes Embryologic Restrictions when
      Performing Infrapyloric Lymphadenectomy in Laparoscopic Gastric Cancer Surgery.

PMID- 25998090
TI  - Arabidopsis seed mucilage secretory cells: regulation and dynamics.
AB  - Seeds from various angiosperm species produce polysaccharide mucilage
      facilitating germination and, therefore, conferring major evolutionary
      advantages. The seed epidermal mucilage secretory cells (MSCs) undergo numerous
      tightly controlled changes of their extracellular matrixes (ECMs) throughout seed
      development. Recently, major progress based on the model species Arabidopsis
      thaliana was published, including the identification of 54 genes necessary for
      mucilage synthesis and release. Here, we review these genes that constitute the
      so-called 'MSC toolbox', within which transcription factors and proteins related
      to polysaccharide production, secretion, modification, and stabilization are the
      most abundant and belong to complex regulatory networks. We also discuss how seed
      coat 'omics data-mining, comparative genomics, and operon-like gene cluster
      studies will provide means to identify new members of the MSC toolbox. 

PMID- 25998089
TI  - Expression of miRNAs in response to freezing and anoxia stresses in the freeze
      tolerant fly Eurosta solidaginis.
AB  - Insect cold hardiness is associated with substantial metabolic rate suppression,
      often including developmental diapause as well as metabolic suppression imposed
      by freezing and freeze-associated oxygen limitation. MicroRNAs, small non-coding
      transcripts that bind to mRNA, are known modulators of hypometabolism in freeze
      tolerant insects. To further contribute to the growing signature of stress
      responsive miRNAs, this study amplified and quantified changes in the expression
      levels of four microRNA species, miR-8, miR-9, miR-92b and miR-277, in response
      to freezing or anoxia exposures of freeze tolerant gall fly larvae, Eurosta
      solidaginis. MiR-92b levels were significantly elevated by 1.57-fold in frozen E.
      solidaginis at -15 degrees C as compared with 5 degrees C controls, whereas miR
      92b levels were significantly reduced in anoxic E. solidaginis to levels that
      were 0.77-fold as compared with larvae held under normoxic conditions. The other
      miRNAs investigated showed no significant changes in stressed larvae. These data
      demonstrate differential miR-92b expression in frozen/anoxic versus control
      insect larvae and position this miRNA as a stress responsive marker in this model
      insect. 

PMID- 25998091
TI  - Editorial overview: Energy biotechnology.

PMID- 25998092
TI  - The diet-induced metabolic syndrome is accompanied by whole-genome epigenetic
      changes.
AB  - Consuming a high-fat/high-fructose diet (HFD) starting at a young age leads to
      the development of obesity and to the progression of metabolic syndrome (MS). We
      are interested in the relationship between MS and DNA methylation as a mediator
      of the metabolic memory and the early appearance of these diseases in the
      progeny. To this end, Wistar rats were fed a HFD for 1 year, and every 12 weeks,
      biochemical analyses were performed. After 24 weeks, animals fed the HFD showed
      alterations related to MS such as elevated blood levels of fasting glucose,
      triglycerides, and insulin compared with their littermate controls. During the
      experimental period, the control females exhibited a 40 % lower 5-methylcytosine
      (5-mC) level compared to the control males. The HFD affected the 5-mC levels in
      males and females differently. The HFD induced a 20 % decrease in the 5-mC levels
      in males and a 15 % increase in females. We found that the HFD induces an early
      presentation of MS in the progeny of treated animals and that the DNA methylation
      was altered in the F1 generation. The presentation of MS is positively associated
      with changes in the global percentage of 5-mC in the DNA. 

PMID- 25998093
TI  - Memantine in the prevention or alleviation of electroconvulsive therapy induces
      cognitive disorders: A placebo controlled trial.
AB  - The purpose of this study was to evaluate the effect of memantine administration
      on the adverse cognitive effects of electroconvulsive therapy (ECT). Forty
      patients diagnosed with a major depressive disorder for which ECT was indicated
      as a treatment for their current episode were randomly allocated to either the
      memantine (5mg/day) group or the placebo group. All patients underwent the same
      protocol for anaesthesia and ECT procedures. The patients received memantine or
      the placebo for the whole period of ECT treatment, starting the day before ECT
      and continuing until the fourth session of ECT. The Modified Mental State
      Examination (MMSE) was used for the assessment of cognition before and after the
      trial. Regarding MMSE and item 3 MMSE (related to recent memory), the memantine
      group scored significantly higher at the end of ECT sessions than the control
      group (P=0.02, P<0.001, respectively). Our data support the hypothesis that
      memantine may reduce cognitive impairment following ECT. Memantine could be both
      a safe and well-tolerated treatment for use with ECT. 

PMID- 25998094
TI  - Spouses of male psychiatric patients are more prone to intimate partner violence.
AB  - Intimate partner violence (IPV) is a great public health concern. Most studies
      have evaluated different risk factors of IPV in general population, but few have
      evaluated the perpetration of IPV by subjects with psychological disease. We
      evaluated the prevalence of IPV among spouses of men with psychiatric disease. In
      this descriptive study, we questioned 119 women whose husbands were in-patient or
      out-patients of psychology clinic. A validated questionnaire was used for
      evaluation IPV and its different subtypes. All women reported to encounter some
      kind of IPV in some periods. Women reported emotional abuse in 100%, physical
      abuse in 99.2% and sexual abuse in 81.5%. None of the patients were eager to tell
      anyone about being victim of IPV due to religious beliefs, society culture and
      believing in their marital status and trying to keep their marriage. IPV is
      higher among families with men having psychological disease. Policy makers and
      clinicians should predominantly target these families. Also, empowering women may
      reduce the risk of intimate partner violence. 

PMID- 25998095
TI  - Prevalence of depression and its correlates among undergraduates in Sri Lanka.
AB  - AIMS: There is a dearth of mental health research on undergraduates in Sri Lanka.
      This study examines the prevalence of depression in a sample of Sri Lankan
      undergraduates, their exposure to threatening life events and the predictors of
      their depression. METHODS: Responses of 4304 undergraduates were obtained on the
      Patient Health Questionnaire-9 and a measure of exposure to threatening life
      events, with binary logistic regression models used to identify the demographic
      and life event correlates of screening positive for Major Depressive Disorder
      (MDD). RESULTS: PHQ-9 diagnoses of 'Major' and 'Other' depression were obtained
      by 9.3% and 13.5% of undergraduates, respectively. A higher likelihood of MDD was
      seen among those who were older and those living in hostels (compared to home),
      although no differences were seen between genders or those studying in different
      faculties. Likelihood of MDD was higher in undergraduates exposed to multiple
      threatening life events as well as those exposed to physical threat; family
      deaths; romantic break-ups; a problem with a close associate; educational
      difficulties; unemployment and domestic violence, and among male undergraduates
      harassed by another student. CONCLUSIONS: MDD is prevalent in these
      undergraduates and universities need to develop services to assist them. Such
      services may also need to focus on supporting those who have experienced
      threatening life events, particularly those that arise as a result of being an
      undergraduate, as these may increase the risk of MDD.

PMID- 25998096
TI  - Endocrine disruptors and female cancer: Informing the patients (Review).
AB  - Pollutants altering the endocrine system, known as endocrine disruptors (ED), may
      modify the risk of female cancers. The carcinogenic effect of ED on humans has
      been confirmed by experimental studies for various substances including
      pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as
      heavy metals, but it is difficult to quantify precisely for several reasons
      hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that
      manifests itself over a long period of time, making difficult the detection of
      the specific contribution of the pollutants, whose absorbed dose is often
      unknown. The combined effect of various substances leads to complex interactions
      whose outcome is difficult to predict. These substances may accumulate and carry
      out their harmful effect on critical periods of life, probably also at doses
      considered harmless to an adult. ED can also have epigenetic adverse effects on
      the health of future generations. In conclusion, the carcinogenic effects of
      endocrine disruptors on female cancer types is plausible although additional
      studies are needed to clarify their mechanisms and entities. In the last part of
      the review we suggest ways to reduce ED exposure as it is mandatory to implement
      necessary measures to limit exposure, particularly during those periods of life
      most vulnerable to the impact of oncogenic environmental causes, such as the
      embryonic period and puberty.

PMID- 25998097
TI  - Identification and evaluation of cochlear implant candidates with asymmetrical
      hearing loss.
AB  - OBJECTIVE: Recommendation for cochlear implant (CI) treatment for individuals
      with severe to profound single-sided deafness (SSD) and asymmetrical hearing loss
      (AHL) is on the rise. This raises the need for greater consistency in the
      definition of CI candidacy for these cases and in the assessment methods of
      patient-related benefits to permit effective comparison and interpretation of the
      outcomes with both conventional and implantable options across studies. METHOD:
      During a dedicated seminar on implant treatment in AHL patients, the panellists
      of the closing round table reviewed the clinical experience presented with the
      aim to define clear audiometric characteristics for both AHL and SSD cases, as
      well as a common data set enabling consistent evaluation of hearing benefits in
      this population. CONCLUSIONS: The panellists agreed on a clear differentiation
      between AHL and SSD CI candidates, defining average pure-tone thresholds up to 4
      kHz for better and poorer ears. Agreement was reached on a minimum set of
      assessment procedures, and included the necessity of trials with conventional
      CROS/BICROS hearing aids and bone conduction devices before considering CI
      treatment. Objective assessment of sound localisation abilities was identified as
      the most relevant criterion to quantify performance before and after treatment.
      In parallel, subjective assessment of overall hearing ability was recommended via
      the Speech, Spatial and Qualities of hearing questionnaire. Longitudinal follow
      up of these parameters and the hours of daily use were considered essential to
      reflect the potential treatment benefits for this population. The consistency in
      the data collection and its report will further support health authorities in
      their decision on acceptable gains from available hearing loss treatment options.

PMID- 25998098
TI  - Genes Encoding Vascular Endothelial Growth Factor A (VEGF-A) and VEGF Receptor 2
      (VEGFR-2) and Risk for Bronchopulmonary Dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the main consequences of
      prematurity, with notably high heritability. Vascular endothelial growth factor A
      (VEGF-A) and its main receptor, vascular endothelial growth factor receptor 2
      (VEGFR-2), have been implicated in the pathogenesis of BPD. OBJECTIVE: To study
      whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are
      associated with BPD. METHODS: In this association study, six tagging single
      nucleotide polymorphism (tSNPs) for VEGFA and 25 tSNPs for VEGFR2 were genotyped
      in a prospectively collected, genetically homogeneous discovery population of 160
      infants (44 infants with grade 2-3 BPD) born before 30 completed gestational
      weeks. The replication population of 328 infants included 120 cases of BPD.
      RESULTS: VEGFR2 SNP rs4576072 was associated with BPD grade 2-3 with a minor
      allele frequency in 23.9% of the cases compared to 9.1% in controls (p = 0.0005,
      odds ratio 3.15, 95% CI: 1.62-6.12) in the discovery population. This association
      was not observed in the more heterogeneous replication population. CONCLUSIONS:
      In line with the results of recent large-scale genetic studies, our findings
      indicate that common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are
      not consistently associated with BPD. This finding does not rule out the
      involvement of VEGFA and VEGFR2 in BPD pathogenesis since, in addition to common
      variations within the gene region, other mechanisms also play important roles in
      the regulation of gene function.

PMID- 25998099
TI  - K356dup--an in-frame insertion in the BCR-ABL gene in an imatinib-resistant
      chronic myeloid leukemia.

PMID- 25998101
TI  - Multiparity-induced enhancement of hippocampal neurogenesis and spatial memory
      depends on ovarian hormone status in middle age.
AB  - Menopause is associated with cognitive decline, and previous parity can increase
      or delay the trajectory of cognitive aging. Furthermore, parity enables the
      hippocampus to respond to estrogens in middle age. The present study investigated
      how previous parity and estrogens influence cognition, neurogenesis, and neuronal
      activation in response to memory retrieval in the hippocampus of middle-aged
      females. Multiparous and nulliparous rats were ovariectomized (OVX) or received
      sham surgery and were treated with vehicle, 17beta-estradiol, 17alpha-estradiol,
      or estrone. Rats were trained on the spatial working and reference memory
      versions of the Morris water maze. Multiparous rats had a significantly greater
      density of immature neurons in the hippocampus, enhanced acquisition of working
      memory, but poorer reference memory compared with nulliparous rats. Furthermore,
      OVX increased, while treatment with estrogens reduced, the density of immature
      neurons, regardless of parity. OVX improved reference memory only in nulliparous
      rats. Thus, motherhood has long-lasting effects on the neuroplasticity and
      function of the hippocampus. These findings have wide-ranging implications for
      the treatment of age-associated decline in women. 

PMID- 25998102
TI  - Immobilization of immunoglobulin-G-binding domain of Protein A on a gold surface
      modified with biotin ligase.
AB  - Protein A from Staphylococcus aureus specifically binds to the Fc region of
      immunoglobulin G (IgG) and is widely used as a scaffold for the immobilization of
      IgG antibodies on solid supports. It is known that the oriented immobilization of
      Protein A on solid supports enhances its antibody-binding capability in
      comparison with immobilization in a random manner. In the current work, we
      developed a novel method for the oriented immobilization of the IgG-binding
      domain of Protein A based on the biotinylation reaction from archaeon Sulfolobus
      tokodaii. Biotinylation from S. tokodaii has a unique property in that the
      enzyme, biotin protein ligase (BPL), forms a stable complex with its biotinylated
      substrate protein, biotin carboxyl carrier protein (BCCP). Here, BCCP was fused
      to the IgG-binding domain of Protein A, and the resulting fusion protein was
      immobilized on the BPL-modified gold surface of the sensor chip for quartz
      crystal microbalance through complexation between BCCP and BPL. The layer of the
      IgG-binding domain prepared in this way successfully captured the antibody, and
      the captured antibody retained high antigen-binding capability. 

PMID- 25998103
TI  - A continuous tyrosyl-tRNA synthetase assay that regenerates the tRNA substrate.
AB  - Tyrosyl-tRNA synthetase catalyzes the attachment of tyrosine to the 3' end of
      tRNA(Tyr), releasing AMP, pyrophosphate, and l-tyrosyl-tRNA as products. Because
      this enzyme plays a central role in protein synthesis, it has garnered attention
      as a potential target for the development of novel antimicrobial agents. Although
      high-throughput assays that monitor tyrosyl-tRNA synthetase activity have been
      described, these assays generally use stoichiometric amounts of tRNA, limiting
      their sensitivity and increasing their cost. Here, we describe an alternate
      approach in which the Tyr-tRNA product is cleaved, regenerating the free tRNA
      substrate. We show that cyclodityrosine synthase from Mycobacterium tuberculosis
      can be used to cleave the l-Tyr-tRNA product, regenerating the tRNA(Tyr)
      substrate. Because tyrosyl-tRNA synthetase can use both l- and d-tyrosine as
      substrates, we replaced the cyclodityrosine synthase in the assay with d-tyrosyl
      tRNA deacylase, which cleaves d-Tyr-tRNA. This substitution allowed us to use the
      tyrosyl-tRNA synthetase assay to monitor the aminoacylation of tRNA(Tyr) by d
      tyrosine. Furthermore, by making Tyr-tRNA cleavage the rate-limiting step, we are
      able to use the assay to monitor the activities of cyclodityrosine synthetase and
      d-tyrosyl-tRNA deacylase. Specific methods to extend the tyrosyl-tRNA synthetase
      assay to monitor both the aminoacylation and post-transfer editing activities in
      other aminoacyl-tRNA synthetases are discussed. 

PMID- 25998104
TI  - Design and validation of a homogeneous time-resolved fluorescence cell-based
      assay targeting the ligand-gated ion channel 5-HT3A.
AB  - Ligand-gated ion channels (LGICs) are considered as attractive protein targets in
      the search for new therapeutic agents. Nowadays, this strategy involves the
      capability to screen large chemical libraries. We present a new Tag-lite ligand
      binding assay targeting LGICs on living cells. This technology combines the use
      of suicide enzyme tags fused to channels of interest with homogeneous time
      resolved fluorescence (HTRF) as the detection readout. Using the 5-HT3 receptor
      as system model, we showed that the pharmacology of the HALO-5HT3 receptor was
      identical to that of the native receptor. After validation of the assay by using
      5-HT3 agonists and antagonists of reference, a pilot screen enabled us to
      identify azelastine, a well-known histamine H1 antagonist, as a potent 5-HT3
      antagonist. This interesting result was confirmed with electrophysiological
      experiments. The method described here is easy to implement and could be
      applicable for other LGICs, opening new ways for the screening of chemical
      libraries. 

PMID- 25998105
TI  - Visible light-induced singlet oxygen-mediated intracellular disassembly of
      polymeric micelles co-loaded with a photosensitizer and an anticancer drug for
      enhanced photodynamic therapy.
AB  - Herein, we report a biocompatible amphiphilic block copolymer micelle bearing a
      singlet oxygen-sensitive vinyldithioether cleavable linker at the core-shell
      junction, which undergoes singlet oxygen-mediated photocleavage in the presence
      of visible light. The micelle facilitates the light-responsive release of singlet
      oxygen and an anticancer drug for enhanced photodynamic therapy. 

PMID- 25998106
TI  - Comparative study of the biochemical properties of proteasomes in domestic
      animals.
AB  - Information on the biochemical properties of proteasomes is lacking or, at best,
      only fragmentary for most species of veterinary interest. Moreover, direct
      comparison of the limited data available on the enzymatic features of proteasomes
      in domestic animals is rendered difficult due to the heterogeneity of the
      experimental settings used. This represents a clear drawback in veterinary
      research, given the crucial involvement of proteasomes in control of several
      physiological and pathological processes. We performed the first comparative
      analysis of key biochemical properties of proteasomes obtained from 8 different
      domestic mammals. Specifically, we investigated the three main peptidase
      activities of constitutive and immunoproteasomes in parallel and systematically
      checked the sensitivity of the chymotryptic site to three of the most potent and
      selective inhibitors available. Overall, there was substantial similarity in the
      enzymatic features of proteasomes among the species examined, although some
      interesting species-specific features were observed. 

PMID- 25998107
TI  - Predictive Performance of a Vancomycin Population Pharmacokinetic Model in
      Neonates.
AB  - INTRODUCTION: The pharmacokinetics of vancomycin are highly variable among
      neonates, which makes dosing challenging in this population. However, adequate
      drug exposure is critical, especially when treating methicillin-resistant
      Staphylococcus aureus (MRSA) infections. Utilization of population
      pharmacokinetic models and Bayesian methods offers the potential for developing
      individualized therapeutic approaches. To meet this need, a neonatal vancomycin
      population pharmacokinetic model was recently published. The current study sought
      to externally evaluate the predictive performance and generalizability of this
      model. METHODS: A retrospective chart review of neonates who received vancomycin
      and had >=1 peak and >=1 trough concentrations at five Intermountain Healthcare
      neonatal intensive care units from 2006 to 2013 was performed and served as the
      external validation cohort. The published population pharmacokinetic model was
      implemented in NONMEM 7.2 with the structural and variance parameter values set
      equal to the estimates reported previously. The model was then used to predict
      the first peak and trough concentration for each neonate in the validation cohort
      and the model prediction error and absolute prediction error were calculated.
      Normalized prediction distribution errors (NPDE) were also evaluated. RESULTS: A
      total of 243 neonates were studied with a median postmenstrual age of 33 (range:
      23-54) weeks and a median weight of 1.6 (range: 0.4-6.8) kg. The model predicted
      the observed vancomycin concentrations with reasonable precision. For all
      vancomycin concentrations, the median prediction error was -0.8 (95% CI: -1.4 to 
      0.4) mg/L and the median absolute prediction error was 3.0 (95% CI: 2.7-3.5)
      mg/L. No trends in NPDE across weight, postmenstrual age, serum creatinine, or
      time after dose were observed. CONCLUSION: An evaluation of a recently published
      neonatal vancomycin population pharmacokinetic model in a large external dataset
      supported the predictive performance and generalizability of the model. This
      model may be useful in evaluating neonatal vancomycin dosing regimens and
      estimating the extent of drug exposure.

PMID- 25998109
TI  - Strain induced crystallization and melting of natural rubber during dynamic
      cycles.
AB  - Strain-induced crystallization (SIC) of natural rubber (NR) is studied during
      dynamic cycles at high frequencies (with equivalent strain rates ranging from 7.2
      s(-1) to 290 s(-1)). The testing parameters are varied: the frequency, the
      temperature and the stretching ratio domain. It is found that an increase of the
      frequency leads to an unexpected form of the CI-lambda curve, with a decrease of
      the crystallinity during both loading and unloading steps of the cycle.
      Nevertheless, the interpretation of the curves needs to take into account several
      phenomena such as (i) instability of the crystallites generated during the
      loading step, which increases with the frequency, (ii) the memory of the previous
      alignment of the chains, which depends on the minimum stretching ratio of the
      cycle lambdamin and the frequency, and (iii) self-heating which makes the
      crystallite nucleation more difficult and their melting easier. Thus, when the
      stretching ratio domain is above the expected stretching ratio at complete
      melting lambdamelt, the combination of these phenomena, at high frequencies,
      leads to unexpected results such as complete melting at lambdamin, and hysteresis
      in the CI-lambda curves. 

PMID- 25998108
TI  - Expression of Wnt and Notch signaling pathways in inflammatory bowel disease
      treated with mesenchymal stem cell transplantation: evaluation in a rat model.
AB  - INTRODUCTION: The purpose of this study was to investigate the expression of Wnt
      and Notch signaling pathway-related genes in inflammatory bowel disease (IBD)
      treated with mesenchymal stem cell transplantation (MSCT). METHODS: TNBS (2,4,6
      trinitrobenzene sulfonic acid) was used to establish IBD in a rat model.
      Mesenchymal stem cells (MSCs) were transplanted via tail vein transfusion. Saline
      water was used in a control group. The expression of Wnt and Notch main signaling
      molecules was screened by gene chips and verified by quantitative reverse
      transcription-polymerase chain reaction in the IBD rat model on day 14 and day 28
      after transplantation. RESULTS: The IBD rat models were successfully established
      and MSCs were transplanted into those models. Genome-wide expression profile
      chips identified a total of 388 differentially expressive genes, of which 191
      were upregulated and 197 were downregulated in the MSC-transplanted group in
      comparison with the IBD control group. Real-time quantitative polymerase chain
      reaction results showed that the level of Olfm4 mRNA expression in the IBD group
      (2.54+/-0.20) was significantly increased compared with the MSCT group (1.39+/
      0.54) and the normal group (1.62+/-0.25) (P <0.05). The Wnt3a mRNA was more
      highly expressed in IBD rats (2.92+/-0.94) and decreased in MSCT rats (0.17+/
      0.63, P <0.05). The expression of GSK-3beta mRNA was decreased in the setting of
      inflammation (0.65+/-0.04 versus 1.00+/-0.01 in normal group, P <0.05) but
      returned to normal levels after MSCT (0.81+/-0.17). The expression of beta
      catenin was observed to increase in IBD tissues (1.76+/-0.44) compared with
      normal tissues (1.00+/-0.01, P <0.05), but no difference was found in the MSCT
      group (1.12+/-0.36). Wnt11 declined at 14 days and returned to normal levels at
      28 days in the IBD group; in comparison, a significantly lower expression was
      found in MSCT rats. There were no differences in the expression of Fzd3, c-myc,
      TCF4, and Wnt5a in inflammation, but all of those genes declined after MSCT
      treatment. CONCLUSIONS: The canonical Wnt and Notch signaling pathways are
      activated in IBD and may be suppressed by stem cell transplantation to
      differentiate into intestinal epithelium after MSCT. Moreover, the non-canonical
      Wnt signaling may be inhibited by canonical Wnt signaling in the setting of
      inflammation and may also be suppressed by MSCT.

PMID- 25998110
TI  - The frontotemporal dementias.
AB  - Frontotemporal dementia (FTD) is a heterogeneous group of hereditary and sporadic
      neurodegenerative disorders affecting frontotemporal areas. FTD, a leading cause
      of young-onset dementia, is often initially mistaken for primary psychiatric
      disorders. Based on early and predominant symptoms, different clinical syndromes
      can be distinguished: the behavioral variant and 2 variants of progressive
      aphasia; semantic dementia and progressive nonfluent aphasia. Neuropathological
      classification is based on protein accumulation in the brain. Pathogenic
      mutations in different genes have been identified. Specific pharmacological
      treatment is the main research goal. Meanwhile the management must focus on early
      correct diagnosis, symptom alleviation, caregiver support and educational
      interventions. 

PMID- 25998111
TI  - Posterior cortical atrophy: an atypical variant of Alzheimer disease.
AB  - Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by
      striking progressive visual impairment and a pattern of atrophy mainly involving
      posterior cortices. PCA is the most frequent atypical presentation of Alzheimer
      disease. The purpose of this article is to provide a summary of PCA's
      neuropsychiatric manifestations. Emotional and psychotic symptoms are discussed
      in the context of signal characteristic features of the PCA syndrome (the early
      onset, focal loss of visual perception, focal posterior brain atrophy) and the
      underlying cause of the disease. The authors' experience with psychotherapeutic
      intervention and PCA support groups is shared in detail. 

PMID- 25998112
TI  - Rapidly progressive young-onset dementias: neuropsychiatric aspects.
AB  - Rapidly progressive dementia (RPD) is roughly defined as neurocognitive decline
      resulting in dementia or death within 2 years. Although RPDs affect all age
      groups, many occur in patients with young-onset dementia. Although prion disease
      (eg, Creutzfeldt-Jakob disease) is often thought to be the prototypic rapidly
      progressive young-onset dementia, the differential diagnosis is broad and some
      etiologies may be treatable. Hence, an appropriate workup to determine the
      etiology of RPD is crucial to planning the appropriate management. This article
      reviews the differential diagnosis, diagnostic workup, and management
      considerations for this unique patient population.

PMID- 25998113
TI  - Young-onset dementia epidemiology applied to neuropsychiatry practice.
AB  - A substantial number of adults suffer young-onset dementia (YOD). The diversity
      of types and syndromes makes recognition and diagnosis difficult. An algorithmic
      approach to interpreting clinical data, informed by clinical epidemiology,
      integrates data pertaining to defining syndromes and their chronology and tempo,
      family history, and other neuropsychiatric features and neurologic signs, is used
      to reach a preliminary diagnosis and direct diagnostic tests and their
      interpretation. Screening for YOD in the psychiatric context is a rational
      process in which vigilance is combined with careful searches for red flags that
      signal a neurodegenerative etiology. 

PMID- 25998114
TI  - The neuropsychiatric examination of the young-onset dementias.
AB  - Young-onset dementias frequently present with prominent behavioral features and
      constitute a diagnostic challenge. Most cases are secondary to neurodegenerative
      conditions, including the behavioral variant of frontotemporal dementia, which
      has overlapping symptoms with many primary psychiatric disorders. This article
      reviews the differential diagnosis and neuropsychiatric assessment of young-onset
      dementia, which includes detailed history taking, family history, mental status
      examination, office-based cognitive tests, and a focused neurologic examination.
      The clinical examination serves to establish the presence of a dementia and the
      specific clinical syndrome. Biomarkers can be subsequently integrated in a
      probabilistic model to determine the most likely neuropathological process. 

PMID- 25998115
TI  - Neuropsychological assessment and differential diagnosis in young-onset
      dementias.
AB  - Although Alzheimer's disease is the most common cause of dementia in the elderly,
      there are several conditions (ie, frontotemporal dementia or Huntington's
      disease) associated with a relatively earlier onset. This article provides
      arguments in favor of a comprehensive neuropsychological assessment in the
      differential diagnosis of young-onset dementia, as episodic memory impairment is
      not observed early in the course of most types of young-onset dementia that
      predominantly affect the domains of behavior, executive, language, and/or motor
      function. 

PMID- 25998116
TI  - Brain imaging in the differential diagnosis of young-onset dementias.
AB  - Young-onset dementia is a broad category of diseases that affect adults before
      the age of 65, with devastating effects on individuals and families. Neuroimaging
      plays a clear and ever-expanding role in the workup of these diseases. MRI
      demonstrates classic patterns of atrophy that help to confirm the clinical
      diagnosis and may predict the underlying disease. Functional nuclear imaging,
      such as PET, demonstrates areas of brain dysfunction even in the absence of
      visible atrophy. These techniques can inform important aspects of the care of
      young-onset dementia, such as the underlying pathologic condition, treatment, and
      prognosis. 

PMID- 25998117
TI  - Genetic testing and counseling in the diagnosis and management of young-onset
      dementias.
AB  - Young-onset dementia is hereditary, multifactorial, or sporadic. The most common
      hereditary dementias include Alzheimer disease, frontotemporal degeneration,
      Huntington disease, prion diseases, and cerebral autosomal-dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy. Careful attainment of family
      history assists with diagnosis and determining the likelihood of a genetic cause,
      and can direct genetic testing. The type of genetic testing depends on confidence
      of the diagnosis, patient's and affected relatives' symptoms, and the number of
      disease genes. Single gene, disease-specific gene panels, and large dementia
      panels are available. Genetic counseling should be given and informed consent
      obtained. Predictive testing follows the Huntington disease protocol.

PMID- 25998119
TI  - Neuropsychiatric management of young-onset dementias.
AB  - A combination of pharmacologic and nonpharmacologic approaches is necessary for
      the appropriate neuropsychiatric management of patients with young-onset
      dementia. Nonpharmacologic interventions, including psychological management,
      environmental strategies, and caregiver's support, should be the first choice for
      neuropsychiatric management. Pharmacologic interventions differ according to the
      underlying causes of dementia; thus, differential diagnoses are very important.
      Antipsychotics should be prescribed carefully; they should be used for the
      shortest time possible, at the lowest possible dose. 

PMID- 25998118
TI  - The use of cerebrospinal fluid and neuropathologic studies in neuropsychiatry
      practice and research.
AB  - The gold standard for diagnosis of neurodegenerative diseases (ie, Alzheimer
      disease, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies,
      amyotrophic lateral sclerosis) is neuropathologic examination at autopsy. As
      such, laboratory studies play a central role in antemortem diagnosis of these
      conditions and their differentiation from the neuroinflammatory, infectious,
      toxic, and other nondegenerative etiologies (eg, rapidly progressive dementias)
      that are encountered in neuropsychiatric practice. This article summarizes the
      use of cerebrospinal fluid (CSF) laboratory studies in the diagnostic evaluation
      of dementia syndromes and emerging CSF biomarkers specific for underlying
      neuropathology in neurodegenerative disease research. 

PMID- 25998121
TI  - Public advocacy and community engagement: interventions for individuals with
      young-onset dementia and their families.
AB  - Individuals and families affected by young-onset dementia (YOD) deal with
      multiple difficulties related to the altered timing of the dementias. These
      individuals and families are overlooked by the health care and social support
      systems because there are few tailored services/policies for younger people
      affected by dementia. This article suggests how public advocacy and interventions
      at the clinical and community levels can support people living with YOD, in
      particular the spouses, who provide most of the care. 

PMID- 25998120
TI  - The CARE pathway model for dementia: psychosocial and rehabilitative strategies
      for care in young-onset dementias.
AB  - The goal of the Care Pathway Model for Dementia (CARE-D) is to improve quality of
      life and daily functioning both for individuals diagnosed with dementia and for
      their families or other caregivers. This is accomplished by developing
      individualized recommendations focused on a person's strengths and weaknesses as
      determined by formal neurocognitive and psychosocial evaluations. Careful
      attention is given to the stage of illness and an individual's stage in life, to
      connecting families with services that target an individual's cognitive and
      behavioral symptoms, and to providing education and emotional support specific to
      symptoms, clinical diagnosis, and prognosis. 

PMID- 25998122
TI  - The practice and science of young-onset dementias.

PMID- 25998123
TI  - Voiceover Interactive PowerPoint Catheter Care Education for Home Parenteral
      Nutrition.
AB  - BACKGROUND: In home infusions via tunneled catheter/peripherally inserted central
      catheter (TC/PICC) the risk of catheter-related bloodstream infection (CRBSI) and
      complications contribute to rehospitalization and costs. It is unknown if
      voiceover interactive PowerPoint (VOIPP) via digital video disc education
      improves clinical outcomes. MATERIALS AND METHODS: In a quaternary care medical
      center and using a randomized, controlled, 2-group design, hospitalized patients
      with TC/PICC received usual care education or usual care (UC) plus VOIPP
      education prehospital discharge. A multiple-choice 6-item knowledge questionnaire
      was administered preeducation, immediately posteducation, and 7-10 days
      postdischarge. At 90 days, patients were assessed for CRBSI incidence rates per
      1000 catheter-days, rehospitalization, CRBSI-related hospitalization, non-CRBSI
      complications and patient calls to the home parenteral nutrition (HPN)
      clinicians. Analysis of variance, Pearson chi(2), and Kruskal-Wallis test were
      used to compare results between groups. RESULTS: Of 51 patients (UC, n = 27;
      UC+VOIPP, n = 24), mean +/- SD age was 46.3 +/- 14.3 years, 68.6% were female,
      HPN duration was 2.2 +/- 1.01 months, and time to postdischarge test completion
      was 11.5 +/- 5.2 days. There were no baseline differences between groups. Between
      group knowledge and changes in knowledge were similar at preeducation, immediate
      posteducation, and postdischarge (P = .88, 0.30, and 0.37, respectively). There
      were no differences in CRBSI incidence, rehospitalization, CRBSI-related
      rehospitalization rates, and non-CRBSI complications between groups. The UC+VOIPP
      group had more patient calls than did the UC group (21.8 vs 7.7 calls/1000
      catheter-days, P < .001). CONCLUSION: Recorded education led to more patient
      calls to the HPN clinicians; however, there were no differences between groups in
      other outcomes.

PMID- 25998124
TI  - Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal
      Muscle Ryanodine Receptor.
AB  - Type 1 ryanodine receptors (RyR1s) release Ca(2+) from the sarcoplasmic reticulum
      to initiate skeletal muscle contraction. The role of RyR1-G4934 and -G4941 in the
      pore-lining helix in channel gating and ion permeation was probed by replacing
      them with amino acid residues of increasing side chain volume. RyR1-G4934A, 
      G4941A, and -G4941V mutant channels exhibited a caffeine-induced Ca(2+) release
      response in HEK293 cells and bound the RyR-specific ligand [(3)H]ryanodine. In
      single channel recordings, significant differences in the number of channel
      events and mean open and close times were observed between WT and RyR1-G4934A and
      -G4941A. RyR1-G4934A had reduced K(+) conductance and ion selectivity compared
      with WT. Mutations further increasing the side chain volume at these positions
      (G4934V and G4941I) resulted in reduced caffeine-induced Ca(2+) release in HEK293
      cells, low [(3)H]ryanodine binding levels, and channels that were not regulated
      by Ca(2+) and did not conduct Ca(2+) in single channel measurements.
      Computational predictions of the thermodynamic impact of mutations on protein
      stability indicated that although the G4934A mutation was tolerated, the G4934V
      mutation decreased protein stability by introducing clashes with neighboring
      amino acid residues. In similar fashion, the G4941A mutation did not introduce
      clashes, whereas the G4941I mutation resulted in intersubunit clashes among the
      mutated isoleucines. Co-expression of RyR1-WT with RyR1-G4934V or -G4941I
      partially restored the WT phenotype, which suggested lessening of amino acid
      clashes in heterotetrameric channel complexes. The results indicate that both
      glycines are important for RyR1 channel function by providing flexibility and
      minimizing amino acid clashes. 

PMID- 25998125
TI  - An Ankyrin-G N-terminal Gate and Protein Kinase CK2 Dually Regulate Binding of
      Voltage-gated Sodium and KCNQ2/3 Potassium Channels.
AB  - In many mammalian neurons, fidelity and robustness of action potential generation
      and conduction depends on the co-localization of voltage-gated sodium (Nav) and
      KCNQ2/3 potassium channel conductance at the distal axon initial segment (AIS)
      and nodes of Ranvier in a ratio of ~40 to 1. Analogous "anchor" peptides within
      intracellular domains of vertebrate KCNQ2, KCNQ3, and Nav channel alpha-subunits
      bind Ankyrin-G (AnkG), thereby mediating concentration of those channels at AISs
      and nodes of Ranvier. Here, we show that the channel anchors bind at overlapping
      but distinct sites near the AnkG N terminus. In pulldown assays, the rank order
      of AnkG binding strength is Nav1.2 ? KCNQ3 > KCNQ2. Phosphorylation of KCNQ2 and
      KCNQ3 anchor domains by protein kinase CK2 (CK2) augments binding, as previously
      shown for Nav1.2. An AnkG fragment comprising ankyrin repeats 1 through 7 (R1-7)
      binds phosphorylated Nav or KCNQ anchors robustly. However, mutational analysis
      of R1-7 reveals differences in binding mechanisms. A smaller fragment, R1-6,
      exhibits much-diminished KCNQ3 binding but binds Nav1.2 well. Two lysine residues
      at the tip of repeat 2-3 beta-hairpin (residues 105-106) are critical for Nav1.2
      but not KCNQ3 channel binding. Another dibasic motif (residues Arg-47, Arg-50) in
      the repeat 1 front alpha-helix is crucial for KCNQ2/3 but not Nav1.2 binding.
      AnkG's alternatively spliced N terminus selectively gates access to those sites,
      blocking KCNQ but not Nav channel binding. These findings suggest that the 40:1
      Nav:KCNQ channel conductance ratio at the distal AIS and nodes arises from the
      relative strength of binding to AnkG. 

PMID- 25998126
TI  - A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to
      Stimulate Regulatory Frameshifting on Antizyme mRNA.
AB  - The protein antizyme is a negative regulator of cellular polyamine concentrations
      from yeast to mammals. Synthesis of functional antizyme requires programmed +1
      ribosomal frameshifting at the 3' end of the first of two partially overlapping
      ORFs. The frameshift is the sensor and effector in an autoregulatory circuit.
      Except for Saccharomyces cerevisiae antizyme mRNA, the frameshift site alone only
      supports low levels of frameshifting. The high levels usually observed depend on
      the presence of cis-acting stimulatory elements located 5' and 3' of the
      frameshift site. Antizyme genes from different evolutionary branches have evolved
      different stimulatory elements. Prior and new multiple alignments of fungal
      antizyme mRNA sequences from the Agaricomycetes class of Basidiomycota show a
      distinct pattern of conservation 5' of the frameshift site consistent with a
      function at the amino acid level. As shown here when tested in
      Schizosaccharomyces pombe and mammalian HEK293T cells, the 5' part of this
      conserved sequence acts at the nascent peptide level to stimulate the
      frameshifting, without involving stalling detectable by toe-printing. However,
      the peptide is only part of the signal. The 3' part of the stimulator functions
      largely independently and acts at least mostly at the nucleotide level. When
      polyamine levels were varied, the stimulatory effect was seen to be especially
      responsive in the endogenous polyamine concentration range, and this effect may
      be more general. A conserved RNA secondary structure 3' of the frameshift site
      has weaker stimulatory and polyamine sensitizing effects on frameshifting. 

PMID- 25998127
TI  - Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via
      Sorbitol Accumulation and Igf1 Protein Down-regulation.
AB  - Diabetes mellitus (DM) is frequently accompanied by complications, such as
      peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating
      peripheral nerve function and conduction velocity; however, changes in Schwann
      cell differentiation status in DM are not fully understood. Here, we report that
      Schwann cells de-differentiate into immature cells under hyperglycemic conditions
      as a result of sorbitol accumulation and decreased Igf1 expression in those
      cells. We found that de-differentiated Schwann cells could be re-differentiated
      in vitro into mature cells by treatment with an aldose reductase inhibitor, to
      reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo
      DM models exhibited significantly reduced nerve function and conduction, Schwann
      cell de-differentiation, peripheral nerve de-myelination, and all conditions were
      significantly rescued by aldose reductase inhibitor or vitamin D3 administration.
      These findings reveal mechanisms underlying pathological changes in Schwann cells
      seen in DM and suggest ways to treat neurological conditions associated with this
      condition. 

PMID- 25998128
TI  - Phosphorylation of the Hippo Pathway Component AMOTL2 by the mTORC2 Kinase
      Promotes YAP Signaling, Resulting in Enhanced Glioblastoma Growth and
      Invasiveness.
AB  - The mechanistic target of rapamycin (mTOR) and Hippo signaling pathways are two
      major signaling cascades that coordinately regulate cell growth and
      proliferation. Dysregulation of these pathways plays a critical role in
      gliomagenesis. Recent reports have provided evidence of cross-talk between the
      mTOR and Hippo pathways; however, a complete description of the signaling
      relationships between these pathways remains to be elucidated. Utilizing a gene
      trapping strategy in a mouse glioma model, we report the identification of AMOTL2
      as a candidate substrate for mTORC2. AMOTL2 is phosphorylated at serine 760 by
      mTORC2. Mutation of AMOTL2 mimicking constitutive Ser(760) phosphorylation blocks
      its ability to bind and repress YAP leading to increased relative expression of
      known YAP gene targets. Moreover, overexpression of AMOTL2 or a
      nonphosphorylatable AMOTL2-S760A mutant inhibited YAP-induced transcription, foci
      formation, growth, and metastatic properties, whereas overexpression of a
      phosphomimetic AMOTL2-S760E mutant negated these repressive effects of AMOTL2 in
      glioblastoma (GBM) cells in vitro. Similar effects on xenograft growth were
      observed in GBM cells expressing these AMOTL2 Ser(760) mutants. YAP was also
      shown to be required for Rictor-mediated GBM growth and survival. Finally, an
      analysis of mTORC2/AMOTL2/YAP activities in primary GBM samples supported the
      clinical relevance of this signaling cascade, and we propose that pharmacological
      agents cotargeting these regulatory circuits may hold therapeutic potential. 

PMID- 25998129
TI  - Small RNA and degradome sequencing reveals important microRNA function in
      Astragalus chrysochlorus response to selenium stimuli.
AB  - Selenium (Se), an essential element, plays important roles in human health as
      well as environmental sustainability. Se hyperaccumulating plants are thought as
      an alternative selenium resource, recently. Astragalus species are known as
      hyperaccumulator of Se by converting it to nonaminoacid compounds. However, Se
      metabolism-related hyperaccumulation is not elucidated in plants yet. MicroRNAs
      (miRNAs) are key molecules in many biological and metabolic processes via
      targeting mRNAs, which may also play an important role in Se accumulation in
      plants. In this study, we identified 418 known miRNAs, belonging to 380 families,
      and 151 novel miRNAs induced by Se exposure in Astragalus chyrsochlorus callus.
      Among known miRNAs, the expression of 287 families was common in both libraries,
      besides 71 families were expressed only in Se-treated sample, whereas 60
      conserved families were expressed in control tissue. miR1507a, miR1869 and
      miR2867-3p were mostly up-regulated, whereas miR1507-5p and miR8781b were
      significantly down-regulated by Se exposure. Computational analysis shows that
      the targets of miRNAs are involved in different types of biological mechanisms
      including 47 types of cellular component, 103 types of molecular function and 144
      types of biological process. Degradome analysis shows that 1256 mRNAs were
      targeted by 499 miRNAs. We conclude that some known and novel miRNAs such as
      miR167a, miR319, miR1507a, miR4346, miR7767-3p, miR7800, miR9748 and miR-n93
      target transcription factors, disease resistance proteins and some specific genes
      like cysteine synthase and might be related to plant hormone signal transduction,
      plant-pathogen interaction and sulphur metabolism pathways. 

PMID- 25998130
TI  - In vitro biomechanical testing of different configurations of acrylic external
      skeletal fixator constructs.
AB  - OBJECTIVE: To evaluate the in vitro biomechanical properties of four different
      configurations of acrylic external skeletal fixator constructs. MATERIALS AND
      METHODS: Simulated bone constructs were prepared using two segments of 20 mm
      ultra-high-density polyethylene rods with a gap of 5 mm. The full pins (1.5 mm)
      were passed through the proximal and distal segments of ultra-high-density
      polyethylene rods, in the same plane, parallel to each other in configuration U,
      and were crossed in the M1, M2 and C configurations at a 90 degrees  angle to
      each other. Configuration U was a single bilateral uniplanar construct, M1 was a
      double orthogonal bilateral construct, M2 was a double orthogonal bilateral
      construct with proximal and distal connecting articulations, and C was a double
      orthogonal bilateral construct with proximal and distal circumferential
      articulations. Temporary scaffolds of different external skeletal fixator
      configurations were constructed using commercially available polyvinyl chloride
      pipes (20 mm) connected and secured to the fixation pins at a fixed distance from
      the rods. Acrylic powder (polymer) mixed with liquid (monomer) was poured into
      the pipes and allowed to solidify to form the side bars and rings. The external
      skeletal fixator constructs were then subjected to axial compression, cranio
      caudal three-point bending and torsion (n = 4 each) using a universal testing
      machine. Mechanical parameters, namely stress, strain, modulus of elasticity,
      stiffness and bending moment of fixator constructs, were determined from load
      displacement curves. RESULTS: Configuration U was the weakest and configuration C
      was the strongest under all the testing modes. Under compression, the M1, M2 and
      C configurations were similar. Under bending, a significant difference was
      observed among the uniplanar, multiplanar and circular configurations with no
      difference between M1 and M2. However, under torsion, all the external skeletal
      fixator configurations differed significantly. CLINICAL SIGNIFICANCE: The
      freeform external skeletal fixator using acrylic as a replacement for a metallic
      bar may be useful to treat bone fractures and luxations in small animals, as it
      is mechanically strong, lightweight, economical, and pins can be passed from any
      direction depending upon the clinical situation.

PMID- 25998131
TI  - Total Hip Arthroplasty in Haemophilic Patients with Modern Cementless Implants.
AB  - Hip arthropathy due to recurrent haemarthrosis in patients with haemophilia can
      be disabling. When severe degeneration occurs, total hip arthroplasty is
      indicated. Reported outcomes are variable and out of date. The aim of this study
      is to evaluate the survivorship of Total Hip Arthroplasty performed in a patient
      population with modern cementless implants. Twenty-three haemophilic patients
      were treated and followed by a multidisciplinary team dedicated to haemophilia.
      The mean age was 40.6 years. No failures or complications were recorded at a mean
      follow-up of 8.1 years (range: 3.1-13.7). A multidisciplinary team and the use of
      modern cementless implants may represent the keys to achieve good outcomes, fewer
      complications, and better survivorship in the approach to these difficult cases.

PMID- 25998132
TI  - Differentiating Transient Idiopathic Hyperglycaemia and Neonatal Diabetes
      Mellitus in Preterm Infants.
AB  - BACKGROUND/AIMS: Transient idiopathic hyperglycaemia (TIH) is partly due to
      defective processing of proinsulin to insulin in preterm neonates, whereas
      transient neonatal diabetes mellitus (TNDM) is a rare genetic form of pancreatic
      beta-cell dysfunction. Distinguishing these two conditions is difficult yet
      essential to allow personalised management and genetic testing. Here we
      investigated whether metabolic or therapeutic features contributed to the
      diagnosis in preterm neonates. METHODS: We prospectively included 13 preterm
      neonates with TIH between 2008 and 2011, and we identified 2 patients with TNDM
      in the French neonatal diabetes cohort registry. All of them were born before 32
      weeks of gestation. We compared clinical features, glycaemic profiles, insulin
      dosages, and nutritional intakes. RESULTS: TNDM patients had higher day-1
      glycaemia levels before insulin therapy [median 23.5 (20-27) vs. 13.6 (10.7-19.8)
      mmol/l, p = 0.025] and higher insulin requirements [median 1.2 (0.9-1.5) vs. 0.8
      (0.3-0.9) IU/kg/day, p = 0.037] compared to TIH. They also required insulin
      therapy earlier [median 0.75 (0.5-1) vs. 2 (0.5-7) days, p = 0.036] and for a
      longer time [median 85 (57-113) vs. 11 (4-15) days, p = 0.036]. CONCLUSION: TNDM
      and TIH are different clinical and genetic entities with specific
      pathophysiological mechanisms. Metabolic and therapeutic features may help to
      detect TNDM in preterm neonates as soon as day-1 of hyperglycaemia.

PMID- 25998133
TI  - Robust and exact structural variation detection with paired-end and soft-clipped
      alignments: SoftSV compared with eight algorithms.
AB  - Structural variation (SV) plays an important role in genetic diversity among the
      population in general and specifically in diseases such as cancer. Modern next
      generation sequencing (NGS) technologies provide paired-end sequencing data at
      high depth with increasing read lengths. This development enabled the analysis of
      split-reads to detect SV breakpoints with single-nucleotide resolution. But
      ambiguous mappings and breakpoint sequences with further co-occurring mutations
      hamper split-read alignments against a reference sequence. The trade-off between
      high sensitivity and low false-positive rate is problematic and often requires a
      lot of fine-tuning of the analysis method based on knowledge about its algorithm
      and the characteristics of the data set. We present SoftSV, a method for exact
      breakpoint detection for small and large deletions, inversions, tandem
      duplications and inter-chromosomal translocations, which relies solely on the
      mutual alignment of soft-clipped reads within the neighborhood of discordantly
      mapped paired-end reads. Unlike other SV detection algorithms, our approach does
      not require thresholds regarding sequencing coverage or mapping quality. We
      evaluate SoftSV together with eight approaches (Breakdancer, Clever, CREST,
      Delly, GASVPro, Pindel, Socrates and SoftSearch) on simulated and real data sets.
      Our results show that sensitive and reliable SV detection is subject to many
      different factors like read length, sequence coverage and SV type. While most
      programs have their individual drawbacks, our greedy approach turns out to be the
      most robust and sensitive on many experimental setups. Sensitivities above 85%
      and positive predictive values between 80 and 100% could be achieved consistently
      for all SV types on simulated data sets starting at relatively short 75 bp reads
      and low 10-15* sequence coverage.

PMID- 25998134
TI  - Maintenance of a reliable laboratory service for tuberculosis intervention in
      Papua New Guinea.
AB  - The reemergence of tuberculosis, including multidrug-resistant strains, in Papua
      New Guinea highlights the never ending nature of the antituberculosis (anti-TB)
      campaign in that country and warrants the need for constant vigilance against the
      condition. Through surveillance, early detection, and management, the spread and
      incidence of TB can be kept in check. To maintain successful TB control programs,
      the government and partners committed to this campaign need to overhaul essential
      aspects of laboratory services. Clinical laboratories play a critical role in
      diagnostics; their functions cannot be substituted nor relegated. It is time to
      end neglect of these services in Papua New Guinea and to arm the laboratories in
      that country with full financial and logistical support so that they can lead the
      campaign against TB. 

PMID- 25998135
TI  - Determination of the enzymatic activity of cytosolic 5'-nucleotidase cN-II in
      cancer cells: development of a simple analytical method and related cell line
      models.
AB  - The cytosolic 5'-nucleotidase (cN-II) has been shown to be involved in the
      response of cancer cells to cytotoxic agents, and the quantification of its
      activity in biological samples is of great interest. In this context, we
      developed and validated an analytical method for determination of cN-II activity
      in cultured cancer cells. This non-radioactive method, using a Hypercarb column
      as stationary phase, was validated with a lower limit of quantification of 0.1
      MUM inosine. We used it to characterize cell line models with modified cN-II
      expression obtained with stable transfections. We show that the short hairpin RNA
      (shRNA)-mediated inhibition of cN-II expression in various malignant blood cells
      is associated with decreased protein expression and enzymatic activity (1.7-6.2
      fold) as well as an increased sensitivity to cytotoxic agents (up to 14-fold). On
      the other hand, expression of green fluorescent protein (GFP)-fused wild type or
      hyperactive mutant (R367Q) cN-II increased the activity and also decreased the
      sensitivity to nucleoside analogues. Our results confirm the biological relevance
      of modulating cN-II in cancer cells, and we present a straightforward validated
      method for the determination of cN-II activity in cellular samples.

PMID- 25998136
TI  - Determination of naturally occurring resveratrol analog trans-4,4'
      dihydroxystilbene in rat plasma by liquid chromatography-tandem mass
      spectrometry: application to a pharmacokinetic study.
AB  - trans-4,4'-Dihydroxystilbene (DHS) is a naturally occurring resveratrol analog
      that displayed promising anti-cancer activities in pre-clinical studies. To
      further probe its therapeutic potential, a sensitive liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method was developed and validated for the
      measurement of DHS in rat plasma using electrospray ionization and multiple
      reaction monitoring in its negative ion mode. This analytical method demonstrated
      excellent linearity (R(2)  > 0.99), selectivity, sensitivity (with a lower limit
      of quantification of 2.0 ng/mL), accuracy (both intra- and inter-day analytical
      recovery within 100 +/- 15%) and precision (both intra- and inter-day relative
      standard deviation within 10%). The pharmacokinetic profiles of DHS were
      subsequently assessed in Sprague-Dawley rats. Following intravenous injection (4
      mg/kg), DHS had a moderate apparent volume of distribution of the central
      compartment (V(c)  = 887 +/- 297 mL/kg), clearance (Cl = 44.7 +/- 5.1 mL/min/kg)
      and a relatively short mean transit time (MTT = 24.1 +/- 8.8 min). When it was
      given as an oral suspension (10 mg/kg), DHS was absorbed slowly (t max 180 or 300
      min) with very limited plasma exposure and absolute oral bioavailability (F =
      2.22 +/- 0.72%). On the other hand, when DHS was fully solubilized by
      hydroxypropyl-beta-cyclodextrin, it was absorbed rapidly (t(max) 30 or 45 min)
      with more than 15-fold increase in maximal plasma concentration (C(max)), plasma
      exposure (AUC(0->last)) and bioavailability (F = 36.3 +/- 4.8%). Statistical
      comparison provided clear evidence that DHS was better than resveratrol from the
      perspective of pharmacokinetics. In conclusion, further explorations of DHS as an
      anti-cancer agent are warranted.

PMID- 25998137
TI  - Electrochemiluminescent DNA sensor based on controlled Zn-mediated grafting of
      diazonium precursors.
AB  - Controlled Zn-mediated grafting of a thin layer of a diazonium salt was used to
      functionalise a carbon electrode with ruthenium(II)-tris-bipyridine (Ru)-labelled
      DNA for use as a capture probe in an electrochemiluminescent genosensor. A
      secondary reporter probe was labelled with a ferrocene (Fc) molecule, and in the
      presence of the single-stranded DNA target a genocomplex formed, where the Fc
      label effectively quenched the electrochemiluminescence of the signal emitted
      from the Ru-label. The spacing of the labels for maximum sensitivity and minimum
      detection limit was optimised, and the signal reproducibility and stability of
      the method was established. 

PMID- 25998138
TI  - Outcomes of Sprint Fidelis and Riata lead extraction: Data from 2 high-volume
      centers.
AB  - BACKGROUND: The Sprint Fidelis (SF) and the Riata (RT) implantable cardioverter
      defibrillator leads have been recalled for premature failure. OBJECTIVE: Data on
      SF and RT extractions are limited; therefore, we performed a pooled analysis to
      compare the safety and efficacy of lead extraction for the SF and RT lead
      families. METHODS: We retrospectively reviewed consecutive patients undergoing
      transvenous extraction of SF and RT leads at Emory University and the University
      of Pittsburgh Medical Center from January 2007 to October 2013. Patients were
      placed into 2 groups based on the presence of an SF or RT lead. The primary
      endpoint was a major procedural complication, defined as death, need for urgent
      cardiac surgery, and hemopericardium or hemothorax that required an intervention.
      RESULTS: A total of 462 patients underwent extraction of recalled leads (SF, n =
      360; RT, n = 102). The mean number of leads extracted in the RT group was higher
      than in the SF group (1.8 +/- 0.9 vs 1.3 +/- 0.7, P < .001), and there was a
      longer implantation time in the RT group (5.5 +/- 2.5 vs 4.3 +/- 2.0 years, P <
      .001). Complete procedural success was higher in the SF group (99.4% vs 96.1%, P
      =.024). Clinical success was similar (SF 99.4% vs RT 97.1%, P = .075). There were
      6 major procedural complications in the entire cohort (1.3%). The rate of major
      complications was not different between the SF and RT groups (SF 1.1% vs RT 2.0%,
      P = .618). Total mortality was 0.65%, with no difference between the groups
      CONCLUSION: Our data from 2 high-volume centers suggest that extraction of SF and
      RT leads is associated with excellent clinical success and a similar rate of
      major procedural complications.

PMID- 25998139
TI  - Cable externalization and electrical failure of the Riata family of implantable
      cardioverter-defibrillator leads: A systematic review and meta-analysis.
AB  - BACKGROUND: The Riata class of defibrillator leads were placed under US Food and
      Drug Association (FDA) advisory as of November 2011 because of high rates of
      cable externalization (CE) and electrical failure (EF). The overall rates of
      these complications remain unknown. OBJECTIVE: The purpose of this study was to
      systematically search the literature for rates of Riata lead failure and to
      perform a meta-analysis to estimate failure rates. METHODS: We conducted a meta
      analysis of observational studies examining the rates of EF, CE, and the
      interaction of the two. We identified 23 English language manuscripts addressing
      1 or more of these questions. RESULTS: Across 23 studies, the overall CE rate was
      23.1% (95% confidence interval [CI] 19.0%-27.6%). The overall EF rate was 6.3%
      (95% CI 4.7%-8.2%). The presence of CE was associated with a more than 6-fold
      increase in the rate of EF compared to no CE (17.3% [95% CI 11.2%-25.9%] vs 2.7%
      [95% CI 1.4%-5.2%], respectively). The rate of CE was 3-fold higher for 8Fr leads
      compared to 7Fr leads, but rates of EF were similar (4.6%; 95% CI 3.2-6.6] and
      3.9%; 95% CI 2.4-6.1], respectively). Rates of both CE and EF were higher in dual
      coil vs single coil leads, but confidence intervals overlapped. CONCLUSION: In
      clinical practice, rates of CE in Riata leads are substantial. While CE is
      associated with a significant increase in the risk of EF, the incidence of EF
      without externalization is not trivial.

PMID- 25998140
TI  - High prevalence of concealed Brugada syndrome in patients with atrioventricular
      nodal reentrant tachycardia.
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) may coexist with
      Brugada syndrome (BrS). OBJECTIVES: The present study was designed to determine
      the prevalence of drug-induced type 1 Brugada ECG pattern (concealed BrS) in
      patients presenting with clinical spontaneous AVNRT and to investigate their
      electrocardiographic, electrophysiological, and genetic characteristics. METHODS:
      Ninety-six consecutive patients without any sign of BrS on baseline
      electrocardiogram undergoing electrophysiological study and ablation for
      symptomatic, drug-resistant AVNRT and 66 control subjects underwent an ajmaline
      challenge to unmask BrS. Genetic screening was performed in 17 patients
      displaying both AVNRT and BrS. RESULTS: A concealed BrS electrocardiogram was
      uncovered in 26 of 96 patients with AVNRT (27.1%) and in 3 of 66 control subjects
      (4.5%) (P <= .001). Patients with concealed BrS were predominantly female
      patients (n=23 [88.5%] vs n=44 [62.9%], P = .015), had higher prevalence of chest
      pain (n=10 [38.5%] vs n=13 [18.6%], p=0.042), migraine headaches (n=10 [38.5%] vs
      n=10 [14.2%], p=0.008), and drug-induced initiation and/or worsening of duration
      and/or frequency of AVNRT (n=4 [15.4%] vs n=1 [1.4%], p=0.006) as compared to
      patients with AVNRT without BrS. Genetic screening identified 19 mutations or
      rare variants in 13 genes in 13 of 17 patients with both AVNRT and BrS (yield =
      76.5%). Ten of these 13 genotype-positive patients (76.9%) harbored genetic
      variants known or suspected to cause a loss of function of cardiac sodium channel
      current (SCN5A, SCN10A, SCN1B, GPD1L, PKP2, and HEY2). CONCLUSION: Our results
      suggest that spontaneous AVNRT and concealed BrS co-occur, particularly in female
      patients, and that genetic variants that reduce sodium channel current may
      provide a mechanistic link between AVNRT and BrS and predispose to expression of
      both phenotypes.

PMID- 25998141
TI  - Association between incomplete surgical ligation of left atrial appendage and
      stroke and systemic embolization.
AB  - BACKGROUND: Surgical exclusion of the left atrial appendage (LAA) can frequently
      yield incomplete closure. OBJECTIVE: We evaluated the ischemic stroke/systemic
      embolization (SSE) risk in patients with atrial fibrillation (AF) and complete
      LAA closure (cLAA) vs incompletely surgically ligated LAA (ISLL) and LAA stump
      after surgical suture ligation. METHODS: Seventy-two patients (CHA2DS2-VASc score
      4.1 +/- 1.9) underwent surgical LAA ligation in conjunction with mitral valve/AF
      surgery and postoperative LAA evaluation using computerized tomographic
      angiography. RESULTS: Overall, cLAA was detected in 46 of 72 patients (64%), ISLL
      in 17 patients (24%), and LAA stump in 9 patients (12%). The incidences of oral
      anticoagulation (OAC) and recurrent AF were similar among the 3 groups during 44
      +/- 19 months of follow-up. SSE occurred in 2% of patients with cLAA vs 24% with
      ISLL and 0% with LAA stump (P = .006). None of the patients with SSE were
      receiving OAC, and all had recurrent AF during follow-up. Additionally, patients
      with SSE exhibited a significantly smaller ISLL neck diameter (2.8 +/- 1.0 vs 7.1
      +/- 2.1 mm; P = .002). The annualized SSE risk was 1.9% (entire cohort), 6.5%
      (ISLL patients), 14.4% (ISLL patients not receiving OAC), and 19.0% (ISLL neck
      diameter <=5.0 mm) per 100 patient-years of follow-up. The latter risk was nearly
      5 times greater than predicted by conventional risk-stratification schemes.
      Moreover, ISLL emerged as an independent predictor of SSE in univariate analyses
      and as the sole predictor of SSE in a multivariate analysis. CONCLUSION: In
      patients with AF, ISLL is a predictor of SSE, independent of conventional risk
      stratification schemes. Consequently, OAC should be strongly considered in this
      high-risk cohort.

PMID- 25998142
TI  - Towards an international taxonomy of integrated primary care: a Delphi consensus
      approach.
AB  - BACKGROUND: Developing integrated service models in a primary care setting is
      considered an essential strategy for establishing a sustainable and affordable
      health care system. The Rainbow Model of Integrated Care (RMIC) describes the
      theoretical foundations of integrated primary care. The aim of this study is to
      refine the RMIC by developing a consensus-based taxonomy of key features.
      METHODS: First, the appropriateness of previously identified key features was
      retested by conducting an international Delphi study that was built on the
      results of a previous national Delphi study. Second, categorisation of the
      features among the RMIC integrated care domains was assessed in a second
      international Delphi study. Finally, a taxonomy was constructed by the
      researchers based on the results of the three Delphi studies. RESULTS: The final
      taxonomy consists of 21 key features distributed over eight integration domains
      which are organised into three main categories: scope (person-focused vs.
      population-based), type (clinical, professional, organisational and system) and
      enablers (functional vs. normative) of an integrated primary care service model.
      CONCLUSIONS: The taxonomy provides a crucial differentiation that clarifies and
      supports implementation, policy formulation and research regarding the
      organisation of integrated primary care. Further research is needed to develop
      instruments based on the taxonomy that can reveal the realm of integrated primary
      care in practice.

PMID- 25998143
TI  - Tangeretin enhances radiosensitivity and inhibits the radiation-induced
      epithelial-mesenchymal transition of gastric cancer cells.
AB  - Irradiation has been reported to increase radioresistance and epithelial
      mesenchymal transition (EMT) in gastric cancer (GC) cells. The Notch pathway is
      critically implicated in cancer EMT and radioresistance. In the present study, we
      investigated the use of a Notch-1 inhibiting compound as a novel therapeutic
      candidate to regulate radiation-induced EMT in GC cells. According to previous
      screening, tangeretin, a polymethoxylated flavonoid from citrus fruits was
      selected as a Notch-1 inhibitor. Tangeretin enhanced the radiosensitivity of GC
      cells as demonstrated by MTT and colony formation assays. Tangeretin also
      attenuated radiation-induced EMT, invasion and migration in GC cells, accompanied
      by a decrease in Notch-1, Jagged1/2, Hey-1 and Hes-1 expressions. Tangeretin
      triggered the upregulation of miR-410, a tumor-suppressive microRNA. Furthermore,
      re-expression of miR-410 prevented radiation-induced EMT and cell invasion. An in
      vivo tumor xenograft model confirmed the antimetastasis effect of tangeretin as
      we observed in vitro. In nude mice, tumor size was considerably diminished by
      radiation plus tangeretin co-treatment. Tangeretin almost completely inhibited
      lung metastasis induced by irradiation. Tangeretin may be a novel antimetastatic
      agent for radiotherapy.

PMID- 25998145
TI  - Global dynamics of a delayed within-host viral infection model with both virus-to
      cell and cell-to-cell transmissions.
AB  - A within-host viral infection model with both virus-to-cell and cell-to-cell
      transmissions and three distributed delays is investigated, in which the first
      distributed delay describes the intracellular latency for the virus-to-cell
      infection, the second delay represents the intracellular latency for the cell-to
      cell infection, and the third delay describes the time period that viruses
      penetrated into cells and infected cells release new virions. The global
      stability analysis of the model is carried out in terms of the basic reproduction
      number R0. If R0<=1, the infection-free (semi-trivial) equilibrium is the unique
      equilibrium and is globally stable; if R0>1, the chronic infection (positive)
      equilibrium exists and is globally stable under certain assumptions. Examples and
      numerical simulations for several special cases are presented, including various
      within-host dynamics models with discrete or distributed delays that have been
      well-studied in the literature. It is found that the global stability of the
      chronic infection equilibrium might change in some special cases when the
      assumptions do not hold. The results show that the model can be applied to
      describe the within-host dynamics of HBV, HIV, or HTLV-1 infection. 

PMID- 25998144
TI  - The contribution of sensory nerves to cutaneous vasodilatation of the forearm and
      leg to local skin heating.
AB  - PURPOSE: The initial cutaneous vasodilatory response to local skin heating is
      larger in the forearm than the leg. While the initial vasodilatation of the
      forearm to local heating is primarily dependent on sensory nerves, their role in
      the leg is unknown. We compared the contribution of sensory nerves in driving the
      cutaneous vasodilatory response of the forearm and leg to local heating using
      local anaesthetic (EMLA) cream. METHOD: In seven participants, two skin sites
      were selected on both the dorsal forearm and anterolateral calf; one site on each
      region received EMLA, with the other an untreated control. All sites were
      controlled at 33  degrees C and then locally heated to 42  degrees C with
      integrated laser-Doppler local heating probes. RESULTS: Cutaneous vascular
      conductance (CVC) during the initial vasodilatation to local heating was smaller
      in the leg (47 +/- 9% max) compared to the forearm (62 +/- 7 % max) (P = 0.012).
      EMLA reduced the initial vasodilatation at both the leg (27 +/- 13 % max) (P =
      0.02) and forearm (33 +/- 14% max) (P < 0.001). The times to onset of
      vasodilatation, initial vasodilatory peak, and plateau phase were longer in the
      leg compared to the forearm (all P < 0.05), and EMLA increased these times in
      both regions (both P < 0.05). CVC during the plateau phase to sustained local
      skin heating was higher in the leg compared to the forearm at both the untreated
      (93 +/- 6 vs. 85 +/- 4% max) (P = 0.33) and EMLA-treated (94 +/- 5 vs. 86 +/- 6%
      max) (P = 0.001) sites; EMLA did not affect CVC (P > 0.05). CONCLUSION: The
      differences in the initial vasodilatory peak to local skin heating between the
      forearm and the leg are due to the contribution of sensory nerves.

PMID- 25998146
TI  - Comparing the Effectiveness of Total Gastrectomy and Gastric Bypass on Glucose
      Metabolism in Diabetic Rats.
AB  - BACKGROUND: Bariatric surgeries have been widely used in obesity associated type
      II diabetes. However, the mechanisms of surgical treatments for type II diabetes
      in non-obese patients remain controversial. Our study aims to compare the
      effectiveness of various bariatric surgeries in a non-obese diabetic rat model.
      METHODS: Goto-Kakisaki (GK) rats were used to compare the outcome of total
      gastrectomy (TG), Roux-en-Y reconstruction after total gastrectomy (RYTG), and
      Roux-En-Y gastric bypass (RYGB). Body weight, food and water intake, and glucose
      level were monitored prior to and after surgery. Oral glucose tolerance tests
      (OGTT) were performed, and key metabolic hormones were measured at selected time
      points. RESULTS: Despite a significant reduction in body weight in TG and RYTG
      groups, their glucose metabolic rate was not improved. RYGB rats, with only
      moderate reduction in food intake and body weight, had significantly improved
      glucose metabolism. Insulin and ghrelin were significantly reduced in TG and RYTG
      groups, but remained unchanged in RYGB group. CONCLUSIONS: Our study demonstrated
      the effectiveness of RYGB surgery in treating type II diabetes in non-obese
      diabetic rats. These results suggest an important role of gastric system in
      regulating glucose homeostasis.

PMID- 25998147
TI  - Antidementia drug treatment in dementia networks in Germany: use rates and
      factors associated with treatment use.
AB  - BACKGROUND: Dementia networks in Germany constitute a specialised setting for
      integrated dementia care and have shown benefits on relevant outcomes, including
      those of drug treatment. National guidelines recommend treatment with
      acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) or the N
      Methyl-D-Aspartate antagonist (memantine) to reduce cognitive symptoms. However,
      prescription rates are lower than 30 % in general practises. This study aims to
      describe antidementia drug treatment and the factors that are associated with the
      treatment in different dementia networks across Germany. METHODS: We have
      analysed the socio-demographic, clinical and utilisation data from 560 patients
      with dementia (PWD), as well as data from their caregivers, in 13 selected
      dementia networks in Germany. The patients and caregivers were interviewed in
      their homes or in the network facilities. Multiple logistic regression models
      were fitted to evaluate the socio-demographic and clinical factors associated
      with the utilisation of antidementia drug treatment in the various networks.
      RESULTS: In all of the networks in the study, 52 % of the participants received
      an antidementia drug treatment. Factors associated with the utilisation of the
      antidementia drug treatment were: formal diagnosis (OR = 16.81, p < 0.001),
      association with a physician in the network (OR = 3.69, p < 0.001), higher number
      of comorbidities (OR = 0.88, p = 0.039), living alone (OR = 0.51, p = 0.032) and
      higher age (OR = 2.97, p = 0.002). CONCLUSION: Medical treatment of PWD with
      antidementia drugs in dementia networks in Germany is more frequent than in
      primary and nursing home care settings. Our findings also suggest that
      participants with a formal diagnosis and a physician in the network have
      increased rates of receiving antidementia drug treatments. These findings suggest
      that dementia networks focusing on medical treatment should support diagnostic
      procedures and incorporate physician specialists.

PMID- 25998148
TI  - Enablers and barriers to the implementation of primary health care interventions
      for Indigenous people with chronic diseases: a systematic review.
AB  - BACKGROUND: Access to appropriate, affordable, acceptable and comprehensive
      primary health care (PHC) is critical for improving the health of Indigenous
      populations. Whilst appropriate infrastructure, sufficient funding and
      knowledgeable health care professionals are crucial, these elements alone will
      not lead to the provision of appropriate care for all Indigenous people. This
      systematic literature review synthesised international evidence on the factors
      that enable or inhibit the implementation of interventions aimed at improving
      chronic disease care for Indigenous people. METHODS: A systematic review using
      Medical Literature Analysis and Retrieval System Online (MEDLINE) (PubMed
      platform), Web of Science, Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), PsycINFO, Excerpta Medica Database (EMBASE), ATSIHealth,
      Australian Indigenous HealthInfoNet via Informit Online and Primary Health Care
      Research and Information Service (PHCRIS) databases was undertaken. Studies were
      included if they described an intervention for one or more of six chronic
      conditions that was delivered in a primary health care setting in Australia, New
      Zealand, Canada or the United States. Attitudes, beliefs, expectations,
      understandings and knowledge of patients, their families, Indigenous communities,
      providers and policy makers were of interest. Published and unpublished
      qualitative and quantitative studies from 1998 to 2013 were considered.
      Qualitative findings were pooled using a meta-aggregative approach, and
      quantitative data were presented as a narrative summary. RESULTS: Twenty three
      studies were included. Meta-aggregation of qualitative data revealed five
      synthesised findings, related to issues within the design and planning phase of
      interventions, the chronic disease workforce, partnerships between service
      providers and patients, clinical care pathways and patient access to services.
      The available quantitative data supported the qualitative findings. Three key
      features of enablers and barriers emerged from the findings: (1) they are not
      fixed concepts but can be positively or negatively influenced, (2) the degree to
      which the work of an intervention can influence an enabler or barrier varies
      depending on their source and (3) they are inter-related whereby a change in one
      may effect a change in another. CONCLUSIONS: Future interventions should consider
      the findings of this review as it provides an evidence-base that contributes to
      the successful design, implementation and sustainability of chronic disease
      interventions in primary health care settings intended for Indigenous people.

PMID- 25998149
TI  - Quality and Utility of Immediate Formal Postoperative Radiographs in Ankle
      Fractures.
AB  - BACKGROUND: Patients who undergo internal fixation of ankle fractures commonly
      have postoperative imaging performed immediately after surgery. As these patients
      typically are typically immobilized, radiographs provide limited visualization.
      The purpose of this study was to evaluate the utility and quality of formal
      radiographs performed immediately following ankle fracture surgery. METHODS:
      Ankle fractures undergoing open reduction and internal fixation at a single
      institution from January 1, 2011, to January 1, 2013, were reviewed.
      Intraoperative and formal postoperative radiographs were evaluated using defined
      parameters. The postoperative images were compared with the intraoperative
      fluoroscopic images in terms of quality. Postoperative complications were
      evaluated in terms of fracture displacement, hardware malpositioning, and need
      for return to the operating room. A total of 411 patients with 413 ankle
      fractures underwent surgical fixation, with 271 patients undergoing formal
      postoperative radiographs. RESULTS: Twenty-eight patients (10.3%) had 3 good
      quality postoperative views of the ankle, with the lateral (35.2%) and mortise
      (41.3%) views least commonly performed with good technique. None of the patients
      without radiographs had a complication that could have been detected earlier
      using postoperative radiographs. No patients required return to the operating
      room based on immediate postoperative radiographs. Postoperative radiographs cost
      $191 per patient. CONCLUSION: The routine use of formal postoperative radiographs
      prior to discharge from the hospital did not provide additional value to the
      patient or orthopedic surgeon. The quality of these images was generally inferior
      to the quality of those obtained and saved intraoperatively due to malrotation
      and overlying cast material. To reduce cost and radiation exposure, formal
      postoperative radiographs should be obtained only in specific circumstances, such
      as increasing postoperative pain, marginal fixation, or instability. LEVEL OF
      EVIDENCE: Level III, retrospective cohort study.

PMID- 25998150
TI  - Prediction of coning phenomena for irregular particles in paddle dissolution
      test.
AB  - The purpose of the present study was to investigate the applicability of the
      Zwietering equation to predict the occurrence of coning phenomena for non
      spherical, porous, and swell-able particles in the paddle dissolution test. For
      non-spherical particles, the minimum rotation speed at which the coning phenomena
      disappear (no coning rpm, NCrpm) was appropriately predicted by using the Stokes
      diameter or the short side length of the particles. For porous and swell-able
      particles, NCrpm was appropriately predicted by using the Stokes density of the
      particles. The accuracy of the Zwietering equation was sufficient to be used for
      development of a dissolution test method. 

PMID- 25998152
TI  - Lactotransferrin Gene Polymorphism Associated with Caries Experience.
AB  - Dental caries is a common multifactorial disease, resulting from the interaction
      of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF)
      is a main salivary glycoprotein, which modulates the host immune-inflammatory and
      antibacterial response. Although a genetic component for caries outcome has been
      identified, little is known over the genetic aspects underlying its
      susceptibility. Thus, the aim of this study was to investigate the association
      between LTF polymorphisms and caries susceptibility. Six hundred seventy seven 12
      year-old students were selected: 346 with (DMFT >= 1) and 331 without caries
      experience (DMFT = 0). Also, individuals concentrating higher levels of disease
      (polarization group, DMFT >= 2, n = 253) were tested against those with DMFT <= 1
      (n = 424). Along with clinical parameters, three representative LTF tag SNPs
      (rs6441989, rs2073495, rs11716497) were genotyped and the results were evaluated
      using univariate and multivariate analyses. Allele A for tag SNP rs6441989 was
      found to be significantly less frequent in the polarization group, conferring a
      protective effect against caries experience [AA + AG * GG (OR: 0.710, 95% CI:
      0.514-0.980, p = 0.045)], and remained significantly associated with caries
      protection in the presence of gingivitis (p = 0.020) and plaque (p = 0.035).
      These results might contribute to the understanding of the genetic control of
      caries susceptibility in humans.

PMID- 25998151
TI  - Comparison of the neuropsychological mechanisms of 2,6-diisopropylphenol and N
      methyl-D-aspartate receptor antagonist against electroconvulsive therapy-induced
      learning and memory impairment in depressed rats.
AB  - The present study aimed to examine the neurophysiological mechanisms of the 2,6
      diisopropylphenol and N-methyl-D-aspartate (NMDA) receptor antagonist against
      learning and memory impairment, induced by electroconvulsive therapy (ECT). A
      total of 48 adult depressed rats without olfactory bulbs were randomly divided
      into six experimental groups: i) saline; ii) 10 mg/kg MK-801; iii) 10 mg/kg MK
      801 and a course of ECT; iv) 200 mg/kg 2,6-diisopropylphenol; v) 200 mg/kg 2,6
      diisopropylphenol and a course of ECT; and vi) saline and a course of ECT. The
      learning and memory abilities of the rats were assessed using a Morris water maze
      1 day after a course of ECT. The hippocampus was removed 1 day after assessment
      using the Morris water maze assessment. The content of glutamate in the
      hippocampus was detected using high-performance liquid chromatography. The
      expression levels of p-AT8Ser202 and GSK-3beta1H8 in the hippocampus were
      determined using immunohistochemical staining and western blot analysis. The
      results demonstrated that the 2,6-diisopropylphenol NMDA receptor antagonist, MK
      801 and ECT induced learning and memory impairment in the depressed rats. The
      glutamate content was significantly upregulated by ECT, reduced by 2,6
      diisopropylphenol, and was unaffected by the NMDA receptor antagonist in the
      hippocampus of the depressed rats. Tau protein hyperphosphorylation in the
      hippocampus was upregulated by ECT, but was reduced by 2,6-diisopropylphenol and
      the MK-801 NMDA receptor antagonist. It was also demonstrated that 2,6
      diisopropylphenol prevented learning and memory impairment and reduced the
      hyperphosphorylation of the Tau protein, which was induced by eECT. GSK-3beta was
      found to be the key protein involved in this signaling pathway. The ECT reduced
      the learning and memory impairment, caused by hyperphosphorylation of the Tau
      protein, in the depressed rats by upregulating the glutamate content.

PMID- 25998153
TI  - miR-365 overexpression promotes cell proliferation and invasion by targeting
      ADAMTS-1 in breast cancer.
AB  - MicroRNAs (miRNAs) have important roles in the initiation and progression of
      human cancer, including breast cancer. We evaluated miR-365 expression in breast
      cancer tissues, and investigated its effects on cell growth, cell cycle, cell
      invasion, and expression of its target gene ADAMTS-1. miR-365 expression levels
      were analyzed in breast cancer tissues and adjacent normal tissues using qRT-PCR.
      CCK-8, cell cycle, and invasion assays were used to explore the role of miR-365
      expression in breast cancer cells. We conducted luciferase reporter and western
      blot assays to test whether ADAMTS-1 is a direct target of miR-365. We found that
      miR-365 expression levels were significantly higher in breast cancer tissues
      compared with adjacent non-tumor tissues (P<0.05). These relatively high
      expression levels were significantly associated with advanced clinical stages
      (P<0.05). In breast cancer cell lines, transfection with miR-365 inhibitor
      suppressed proliferation and invasion, and resulted in cell cycle arrest.
      Subsequent experiments indicated that miR-365 bound the 3'-UTR of ADAMTS-1 and
      downregulated its expression. Our findings indicated that the inhibition of miR
      365 reduced cell proliferation and cell invasion. Additionally, miR-365 may
      function as a novel oncogene in breast cancer through targeting ADAMTS-1. These
      findings provide insight into the mechanism of breast cancer pathogenesis. 

PMID- 25998154
TI  - Intimal sarcoma of the abdominal aorta with platelet-derived growth factor
      receptor alpha overexpression and amplification in mural invasive cells and
      pulmonary metastatic cells but not in intimal spreading cells.
AB  - Intimal sarcoma (IS) is the most common sarcoma of the aorta. The platelet
      derived growth factor receptor alpha (PDGFRA), murine double minute 2 (MDM2), and
      cyclin-dependent kinase 4 (CDK4) genes are often simultaneously amplified in IS.
      While immunohistochemical analysis of IS tissue has demonstrated frequent
      overexpression of the MDM2 and CDK4 proteins, the expression pattern of PDGFRA
      has not been well characterized, particularly in terms of intratumoral
      heterogeneity. Here, we present the case of a 46-year-old man who presented with
      a backache and was subsequently diagnosed with IS. Intratumoral heterogeneity of
      PDGFRA gene amplification was observed using fluorescence in situ hybridization
      and was positively correlated with PDGFRA protein expression using
      immunohistochemistry (IHC). The expression of PDGFRA was also correlated with
      cytological atypia: PDGFRA was not overexpressed in intimal spreading cells that
      displayed the lowest degree of atypia while PDGFRA overexpression and
      amplification were observed in invasive cells of progressive areas such as the
      aortic wall and a pulmonary metastatic site, which showed increased cytological
      atypia. Although PDGFRA has not been well examined on IHC, IHC of PDGFRA could be
      useful to diagnose IS. However, the areas within the tumor from which specimens
      are derived are important given potential intratumoral heterogeneity. 

PMID- 25998155
TI  - Speciation analysis of mercury in sediments using ionic-liquid-based vortex
      assisted liquid-liquid microextraction combined with high-performance liquid
      chromatography and cold vapor atomic fluorescence spectrometry.
AB  - An improved novel method based on ionic liquid vortex-assisted liquid-liquid
      microextraction has been developed for the extraction of methylmercury,
      ethylmercury and inorganic mercury in sediment samples prior to analysis by high
      performance liquid chromatography with cold vapor atomic fluorescence
      spectrometry. In this work, mercury species were firstly complexed with
      dithizone, and the complexes were extracted into 1-hexyl-3-methylimidazolium
      hexafluorophosphate. Key factors that affect the extraction efficiency of mercury
      species, such as type and amount of ionic liquid and chelatants, extraction time,
      sample pH, salt effect and matrix effect were investigated. Under the optimum
      conditions, linearity was found in the concentration range from 0.1-70 ng/g.
      Limits of detection ranged from 0.037-0.061 ng/g. Reproducibility and recoveries
      were assessed by extracting a series of six independent sediment samples that
      were spiked with different concentration levels. Finally, the proposed method was
      successfully applied in analysis of real sediment samples. In this work, ionic
      liquids vortex-assisted liquid-liquid microextraction was for the first time used
      for the extraction of mercury species in sediment samples. The proposed method
      was proved to be much simpler and more rapid, as well as more environmentally
      friendly and efficient compared with the previous methods. 

PMID- 25998156
TI  - Biomass-derived functional porous carbons as novel electrode material for the
      practical detection of biomolecules in human serum and snail hemolymph.
AB  - The biomass-derived activated carbons (ACs) have been prepared with high surface
      areas up to 793 m(2) g(-1) is by ZnCl2 activation at three different
      temperatures, viz. AC700, AC800, and AC900. The AC samples were characterized by
      a variety of analytical and spectroscopy techniques. The as-synthesized ACs were
      adopted for the simultaneous electrochemical detection of ascorbic acid (AA),
      dopamine (DA), and uric acid (UA). For comparison, reduced graphene oxide (RGO)
      was employed for the proposed sensor. The high surface area, modulated pore size
      and the presence of oxygen surface functional groups like heteroatoms (83.427% C,
      1.085% N, 0.383% S, and 0.861% H) in the biomass-derived AC is found to be
      responsible for the excellent catalytic activities of biomolecules.
      Fascinatingly, the facile sensor further used to detect biomolecules levels in
      the snail hemolymph and human blood serum. Notably, the obtained analytical
      parameters for the biomolecules detection over the AC modified GCE, outperforming
      several carbon-based modified electrodes in literatures.

PMID- 25998157
TI  - The evolution of spatial ordering of oil drops fast spreading on a water surface.
AB  - The design of dynamically self-assembled systems is of high interest in science
      and technology. Here, we report a unique cascade in the self-ordering of droplets
      accompanied by a dewetting transition. The dynamic self-emergent droplets are
      observed when a thin liquid layer of an immiscible fluorocarbon oil
      (perfluorooctyl bromide, PFOB) is placed on a water surface. Due to the gradual
      evaporation of PFOB, a circular PFOB-free domain appears as a result of a local
      dewetting transition. A circular pearling structure is generated at the rim with
      the growth of the dewetting hole. As the next stage, linear arrays of droplets
      are generated in a radial manner from the centre of the hole. These one
      dimensional arrangements then evolve into two-dimensional hexagonal arrays of
      microdroplets through collective rhythmical shrinking/expanding motions. The
      emergence of such dynamic patterns is discussed in terms of the nonlinear
      kinetics of the dewetting transition under thermodynamically dissipative
      conditions. 

PMID- 25998158
TI  - Public health guidelines for physical activity: is there an app for that? A
      review of android and apple app stores.
AB  - BACKGROUND: Physical activity participation is an important behavior for
      modifying lifestyle-related disease risk. Mobile health apps for chronic disease
      management and prevention are being developed at a rapid rate. However, it is
      unclear whether these apps are evidence-based. Current public health
      recommendations for physical activity participation for adults highlight the
      importance of engaging in 150 minutes weekly of purposeful exercise, and muscle
      strengthening activities on at least 2 days of the week. OBJECTIVE: The aims of
      the present review were to (1) identify available evidence-based physical
      activity apps, and (2) identify technological features that could be leveraged to
      improve health outcomes. METHODS: iTunes and Google Play mobile app stores were
      searched using keyword and category searching during a single day (February 18,
      2014) for physical activity apps available in English. The description pages of
      eligible apps were reviewed by 4 independent reviewers for evidence-based
      content, technological, and descriptive features. An a priori subset of apps was
      downloaded for further review (n=6 affiliated with a non-commercial agency; n=10
      top rated; n=10 random selection), and developers were contacted for information
      regarding evidence-informed content. RESULTS: The initial search yielded 2400
      apps, of which 379 apps (n=206 iTunes; n=173 Google Play) were eligible. Primary
      results demonstrated no apps (n=0) adhering to evidence-based guidelines for
      aerobic physical activity, and 7 out of 379 implementing evidence-based
      guidelines for resistance training physical activity. Technological features of
      apps included social networking (n=207), pairing with a peripheral health device
      (n=61), and measuring additional health parameters (n=139). Secondary results
      revealed 1 app that referenced physical activity guidelines (150 minutes/weekly
      of exercise), and demonstrated that apps were based on various physical activity
      reports (n=4) or personal expertise (n=2). CONCLUSIONS: The present study
      demonstrated a shortage of evidence-based physical activity apps. This gap
      underscores the need for development of evidence-informed mobile apps. Results
      highlight the opportunity to develop evidence-informed mobile apps that can be
      used clinically to enhance health outcomes.

PMID- 25998159
TI  - Toward ethically responsible choice architecture in prostate cancer treatment
      decision-making.

PMID- 25998160
TI  - 4-Nonylphenol reduces cell viability and induces apoptosis and ER-stress in a
      human epithelial intestinal cell line.
AB  - 4-Nonylphenol is a widely diffused and stable environmental contaminant,
      originating from the degradation of alkyl phenol ethoxylates, common surfactants
      employed in several industrial applications. Due to its hydrophobic nature, 4
      nonylphenol can easily accumulate in living organisms, including humans, where it
      displays a wide range of toxic effects. Since the gastrointestinal tract
      represents the main route by which 4-nonylphenol enters the body, the intestine
      may be one of the first organs to be damaged by chronic exposure to this
      pollutant through the diet. In the present study, we investigated the effects of
      4-nonylphenol on a human intestinal epithelial cell line (Caco-2 cells). We
      demonstrated that 4-nonylphenol was cytotoxic to cells, as revealed by a decrease
      of the cell number and the decrement of mitochondrial functionality after 24 h of
      treatment. 4-Nonylphenol also reduced the number of cells entering into S-phase
      and interfered with epidermal growth factor signalling, with consequent negative
      effects on cell survival. In addition, 4-nonylphenol induced apoptosis, involving
      the activation of caspase-3, and triggered an endoplasmic reticulum-stress
      response, as revealed by over-expression of GRP78 (78 kDa glucose-regulated
      protein) and activation of XBP1 (X-box binding protein-1). Together, these
      findings support the hypothesis that prolonged exposure to 4-nonylphenol through
      the diet may lead to local damage at the level of intestinal mucosa, with
      potentially negative consequences for intestinal homeostasis and functionality.

PMID- 25998161
TI  - Multiwalled carbon nanotube buckypaper induces cell cycle arrest and apoptosis in
      human leukemia cell lines through modulation of AKT and MAPK signaling pathways.
AB  - MWCNT buckypaper (BP) shows physico-chemical and mechanical properties that make
      it potentially useful as a substrate in nano-bio interface research including in
      tissue engineering. When used as a scaffold material, BP comes into contact with
      host cells and surrounding tissues; therefore it is critical to determine its
      biocompatibility and interaction with living systems. The aim of this study was
      to investigate BP effects on cell growth, apoptosis and reactive oxygen species
      (ROS) production in three human leukemia cell lines HL-60, U-937 and K-562. BP
      was able to induce both the reduction of cell proliferation, associated with an
      arrest in G0/G1 phase of cell cycle and the increase of apoptosis in leukemic
      cell lines, thus exerting both cytostatic and cytotoxic effects. The growth
      inhibitory effect was likely mediated by the decrease of cyclins D, E, A, B1
      levels and CDK4 expression; meanwhile, the apoptotic effect, not mediated by ROS
      production, was presumably due to the combined action of the survival and pro
      apoptotic AKT and MAPK signal transduction pathways. These results raised the
      issue of biocompatibility of MWCNT BP for the creation of carbon nanotubes based
      scaffolds to utilize as prostheses in tissue engineering. 

PMID- 25998162
TI  - Reply to "Albumin infusion in cirrhotic patients with non-SBP infections: End of
      the story?".

PMID- 25998163
TI  - MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly
      targeting FGF5 in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common
      malignancies worldwide. However, the detailed molecular mechanisms underlying HCC
      progression are still not completely clear. Given the crucial role of microRNAs
      (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of
      a metastasis-associated miRNA named miR-188-5p in HCC. METHODS: miRNA array
      analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188
      5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC
      patients and cell lines were evaluated by real-time PCR. The protein expression
      levels were analyzed by Western blot and immunohistochemistry. Luciferase
      reporter assays was used to validate the target of miR-188-5p. The effect of miR
      188-5p on HCC progression was studied in vitro and in vivo. RESULTS: miR-188-5p
      was significantly decreased in HCC and its expression levels were highly
      correlated with multiple nodules, microvascular invasion, overall and disease
      free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell
      proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5
      (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR
      188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5
      expression reversed the inhibitory effects of miR-188-5p on HCC cell
      proliferation and metastasis. CONCLUSIONS: These findings collectively
      demonstrate a tumor suppressor role of miR-188-5p in HCC progression via
      targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic
      biomarker and therapeutic target for HCC.

PMID- 25998164
TI  - Human Atopic Dermatitis Skin-derived T Cells can Induce a Reaction in Mouse
      Keratinocytes in vivo.
AB  - In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T
      cells and keratinocytes is fundamental to the development of chronic lesional
      eczema. The aim of this study was to investigate whether skin-derived T cells
      from AD patients could induce an inflammatory response in mice through
      keratinocyte activation and consequently cause the development of eczematous
      lesions. Punch biopsies of the lesional skin from AD patients were used to
      establish skin-derived T cell cultures, which were transferred to NOD.Cg
      Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous
      injection of the human AD skin-derived T cells resulted in the migration of the
      human T cells from subcutis to the papillary dermis followed by the development
      of erythema and oedema in the mouse skin. Furthermore, the human T cells induced
      a transient proliferative response in the mouse keratinocytes shown as increased
      numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six
      established AD skin-derived T cell cultures, two were superior at inducing a skin
      reaction in the mice, and these cultures were found to contain >10% CCR10(+) T
      cells compared to <2% for the other cultures. In comparison, blood-derived in
      vitro-differentiated Th2 cells only induced a weak response in a few of the mice.
      Thus, we conclude that human AD skin-derived T cells can induce a reaction in the
      mouse skin through the induction of a proliferative response in the mouse
      keratinocytes.

PMID- 25998165
TI  - Chronic traumatic encephalopathy: a potential late and under recognized
      consequence of rugby union?
AB  - The association between exposure to head injury and increased risk of
      neurodegenerative disease, specifically chronic traumatic encephalopathy (CTE),
      is widely recognized. Historically, this was largely considered a phenomenon
      restricted to boxers, with more recent case series identifying further 'high
      risk' individuals, such as former American footballers, or military personnel.
      However, in all cases thus far reported, it is clear that it is the exposure to
      head injury which is associated with increased dementia risk, and not the
      circumstances or environment of exposure. As such, there is considerable
      potential for under-recognition of CTE in patients presenting with
      neurodegenerative disease, particularly where head injury exposure might have
      been historical and through sport. This article reviews current understanding of
      CTE and, via an illustrative case in rugby union, highlights the value of a
      detailed history on head injury and also draws attention to imaging studies in
      assessing patients with neurodegenerative disease. 

PMID- 25998166
TI  - Contribution of neutrophil activation in the differentiation of urine infection
      and contamination in pregnant women.
AB  - BACKGROUND: Urinary tract infections are among the most common bacterial
      infections of humans. Urine culture is the gold standard for asymptomatic
      bacteriuria and pyuria is not always present in bacteriuria, nor is it specific
      for bacteriuria. OBJECTIVE: The aim of the present study was to determine
      neutrophil activation and the contributions of this activation in the
      differentiation of infection and contamination. METHODS: The serum and urine
      myeloperoxidase (MPO) levels of 50 pregnant females with symptoms suggesting UTI
      and 25 healthy non-pregnant control subjects were measured using the enzyme
      linked immunosorbent assay (ELISA) method and the obtained values were compared
      with the results of urine microscopy and urine culture. RESULTS: The leukocyte
      count in urine was significantly higher in group 1 (infection) and group 2
      (contamination) when compared with the control group (group 1 mean: 18.2; group 2
      mean: 14.2; control mean: 4.8; ANOVA test, p <= 0.00). According to the obtained
      ELISA values, a statistical difference in the levels of urine MPO between the
      patient and control groups was seen (p <= 0.00). There was no statistical
      difference among the groups for serum MPO levels (p >= 0.451). CONCLUSION: The
      study findings suggest that standardized measurement techniques such as dipstick
      screening assay for urine MPO level may be useful in differentiating infection
      and contamination, especially in pregnant patients.

PMID- 25998167
TI  - Acceptability of Alternatives to Traditional Emergency Care: Patient
      Characteristics, Alternate Transport Modes, and Alternate Destinations.
AB  - To determine the acceptability of alternatives to traditional emergency care, we
      assessed the proportion of subjects willing to consider alternative modes of
      transportation and alternative destinations. We further identified patient
      characteristics associated with willingness to consider these alternatives. We
      conducted a cross-sectional survey study in the emergency department (ED) of an
      academic medical center. Research assistants screened all non-critically ill ED
      patients for eligibility and willingness to participate and administered an
      interview-based survey that included questions on demographic and clinical
      characteristics, perceived illness severity, and acceptability of alternatives to
      traditional emergency care for acute illness and injuries. We calculated the
      proportions and 95% confidence intervals for subjects who found alternative
      transport modes and destinations acceptable and developed a log-binomial
      regression model to identify patient characteristics associated with
      acceptability of alternative modes of transport and alternative destinations.
      Complete data were available on 1,058 subjects. Forty-two percent of the study
      sample arrived to the ED via emergency medical services (EMS). Over two-thirds of
      the study sample (68.2%) was willing to consider transport via either taxi or
      medical transport van and 69.0% was willing to consider either transportation to
      an urgent care center or their primary care physician's office. Other
      alternatives, including delayed EMS response time, were less frequently endorsed
      as acceptable alternatives. Subject characteristics associated with willingness
      to accept alternative modes of transportation included younger age, chief
      complaint, previous ED use, and place of residence (p < 0.05). Subject
      characteristics associated with willingness to accept alternative destinations
      included younger age, non-white race, lower patient acuity, and lower self
      perceived illness severity (p < 0.05). In our ED, some patients found alternative
      transport modes and alternative destinations acceptable. We identified patient
      level characteristics associated with willingness to accept alternatives;
      however, the predictive ability and clinical utility of these factors is limited.
      Future research should further explore the acceptability and effectiveness of
      these alternative care delivery options.

PMID- 25998169
TI  - High-frequency vibration effect on the stability of a horizontal layer of ternary
      fluid.
AB  - The effect of small-amplitude high-frequency longitudinal vibrations on the
      stability of a horizontal layer of ternary fluid is studied in the framework of
      average approach. Long-wave instability is studied analytically and instability
      to the perturbations with finite wave numbers is studied numerically. It is found
      that, similar to the case when vibrations are absent, for ternary fluids there
      exist monotonic and oscillatory long-wave instability modes. The calculations
      show that the vibrations lead to destabilization in the case of heating from
      below and to stabilization in the case of heating from above. Additionally,
      vibrations influence on the parameter range where long-wave instability is most
      dangerous. New, vibrational, instability modes are found which leads to the
      existence of convection in zero-gravity conditions. 

PMID- 25998168
TI  - Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain
      damage in experimental cerebral malaria.
AB  - INTRODUCTION: Malaria is the most relevant parasitic disease worldwide, and still
      accounts for 1 million deaths each year. Since current antimalarial drugs are
      unable to prevent death in severe cases, new therapeutic strategies have been
      developed. Mesenchymal stromal cells (MSC) confer host resistance against
      malaria; however, thus far, no study has evaluated the therapeutic effects of MSC
      therapy on brain and distal organ damage in experimental cerebral malaria.
      METHODS: Forty C57BL/6 mice were injected intraperitoneally with 5 * 10(6)
      Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received
      saline or bone marrow (BM)-derived MSC (1x10(5)) intravenously and were housed
      individually in metabolic cages. After 4 days, lung and kidney morphofunction;
      cerebrum, spleen, and liver histology; and markers associated with inflammation,
      fibrogenesis, and epithelial and endothelial cell damage in lung tissue were
      analyzed. RESULTS: In P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia
      and mortality; 2) increased phagocytic neutrophil content in brain, even though
      BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment
      detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with
      an increased number of Kupffer cells; 5) decreased kidney damage, without
      effecting significant changes in serum creatinine levels or urinary flow; and 6)
      reduced neutrophil infiltration, interstitial edema, number of myofibroblasts
      within interstitial tissue, and collagen deposition in lungs, resulting in
      decreased lung static elastance. These morphological and functional changes were
      not associated with changes in levels of tumor necrosis factor-alpha,
      keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or
      interferon-gamma, which remained increased and similar to those of P. berghei
      animals treated with saline. BM-MSCs increased hepatocyte growth factor but
      decreased VEGF in the P. berghei group. CONCLUSIONS: BM-MSC treatment increased
      survival and reduced parasitemia and malaria pigment accumulation in spleen,
      liver, kidney, and lung, but not in brain. The two main organs associated with
      worse prognosis in malaria, lung and kidney, sustained less histological damage
      after BM-MSC therapy, with a more pronounced improvement in lung function.

PMID- 25998170
TI  - Apparent wall slip in non-Brownian hard-sphere suspensions.
AB  - We analyze apparent wall slip, the reduction of particle concentration near the
      wall, in hard-sphere suspensions at concentrations well below the jamming limit
      utilizing a continuum level diffusion model. The approach extends a constitutive
      equation proposed earlier with two additional potentials describing the effects
      of gravitation and wall-particle repulsion. We find that although both mechanisms
      are shear independent by nature, due to the shear-rate-dependent counter
      balancing particle migration fluxes, the resulting net effect is non-linearly
      shear dependent, causing larger slip at small shear rates. In effect, this shows
      up in the classically measured flow curves as a mild shear thickening regime at
      the transition from small to intermediate shear rates. 

PMID- 25998171
TI  - Numerical study of laminar, standing hydraulic jumps in a planar geometry.
AB  - We solve the two-dimensional, planar Navier-Stokes equations to simulate a
      laminar, standing hydraulic jump using a Volume-of-Fluid method. The geometry
      downstream of the jump has been designed to be similar to experimental conditions
      by including a pit at the edge of the platform over which liquid film flows. We
      obtain jumps with and without separation. Increasing the inlet Froude number
      pushes the jump downstream and makes the slope of the jump weaker, consistent
      with experimental observations of circular jumps, and decreasing the Reynolds
      number brings the jump upstream while making it steeper. We study the effect of
      the length of the domain and that of a downstream obstacle on the structure and
      location of the jump. The transient flow which leads to a final steady jump is
      described for the first time to our knowledge. In the moderate Reynolds number
      regime, we obtain steady undular jumps with a separated bubble underneath the
      first few undulations. Interestingly, surface tension leads to shortening of
      wavelength of these undulations. We show that the undulations can be explained
      using the inviscid theory of Benjamin and Lighthill (Proc. R. Soc. London, Ser.
      A, 1954). We hope this new finding will motivate experimental verification. 

PMID- 25998172
TI  - Stochastic mechanical degradation of multi-cracked fiber bundles with elastic and
      viscous interactions.
AB  - The mechanics of fiber bundles has been largely investigated in order to
      understand their complex failure modes. Under a mechanical load, the fibers fail
      progressively while the load is redistributed among the unbroken fibers. The
      classical fiber bundle model captures the most important features of this rupture
      process. On the other hand, the homogenization techniques are able to evaluate
      the stiffness degradation of bulk solids with a given population of cracks.
      However, these approaches are inadequate to determine the effective response of a
      degraded bundle where breaks are induced by non-mechanical actions. Here, we
      propose a method to analyze the behavior of a fiber bundle, undergoing a random
      distribution of breaks, by considering the intrinsic response of the fibers and
      the visco-elastic interactions among them. We obtain analytical solutions for
      simple configurations, while the most general cases are studied by Monte Carlo
      simulations. We find that the degradation of the effective bundle stiffness can
      be described by two scaling regimes: a first exponential regime for a low density
      of breaks, followed by a power-law regime at increasingly higher break density.
      For both regimes, we find analytical effective expressions described by specific
      scaling exponents. 

PMID- 25998173
TI  - Clinical pharmacology, creating current and future success in drug development.

PMID- 25998174
TI  - Fermentation of Soybean Meal Hydrolyzates with Saccharomyces cerevisiae and
      Zymomonas mobilis for Ethanol Production.
AB  - Most of the ethanol currently produced by fermentation is derived from sugar
      cane, corn, or beets. However, it makes good ecological and economic sense to use
      the carbohydrates contained in by-products and coproducts of the food processing
      industry for ethanol production. Soybean meal, a co-product of the production of
      soybean oil, has a relatively high carbohydrate content that could be a
      reasonable substrate for ethanol production after fermentable sugars are released
      via hydrolysis. In this research, the capability of Saccharomyces cerevisiae NRRL
      Y-2233 and Zymomonas mobilis subsp. mobilis NRRL B-4286 to produce ethanol was
      evaluated using soybean meal hydrolyzates as substrates for the fermentation.
      These substrates were produced from the dilute-acid hydrolysis of soybean meal at
      135  degrees C for 45 min with 0, 0.5%, 1.25%, and 2% H2 SO4 and at 120  degrees
      C for 30 min with 1.25% H2 SO4 . Kinetic parameters of the fermentation were
      estimated using the logistic model. Ethanol production using S. cerevisiae was
      highest with the substrates obtained at 135  degrees C, 45 min, and 0.5% H2 SO4
      and fermented for 8 h, 8 g/L (4 g ethanol/100 g fresh SBM), while Z. mobilis
      reached its maximum ethanol production, 9.2 g/L (4.6 g ethanol/100 g fresh SBM)
      in the first 20 h of fermentation with the same hydrolyzate. 

PMID- 25998176
TI  - Listening to parents: The role of symptom perception in pediatric palliative home
      care.
AB  - OBJECTIVE: This study analyzes symptom perception by parents and healthcare
      professionals and the quality of symptom management in a pediatric palliative
      home care setting and identifies which factors contribute to a high quality of
      palliative and end-of-life care for children. METHODS: In this retrospective,
      cross-sectional study, parents were surveyed at the earliest three months after
      their child's death. All children were cared for by a specialized home pediatric
      palliative care team that provides a 24/7 medical on-call service. Questionnaires
      assessed symptom prevalence and intensity during the child's last month of life
      as perceived by parents, symptom perception, and treatment by medical staff. The
      responses were correlated with essential palliative care outcome measures (e.g.,
      satisfaction with the care provided, quality-of-life of affected children and
      parents, and peacefulness of the dying phase). RESULTS: Thirty-eight parent dyads
      participated (return rate 84%; 35% oncological disorders). According to parental
      report, dyspnea (61%) and pain (58%) were the dominant symptoms with an overall
      high symptom load (83%). Pain, agitation, and seizures could be treated more
      successfully than other symptoms. Successful symptom perception was achieved in
      most cases and predicted the quality of symptom treatment (R 2, 0.612).
      Concordant assessment of symptom severity between parents and healthcare
      professionals (HCPs) improved the satisfaction with the care provided (p = 0.037)
      as well as the parental quality-of-life (p = 0.041). Even in cases with
      unsuccessful symptom control, parents were very satisfied with the SHPPC team's
      care (median 10; numeric rating scale 0-10) and rated the child's death as highly
      peaceful (median 9). Significance of the results: The quality and the concordance
      of symptom perception between parents and HCPs essentially influence parental
      quality-of-life as well as parental satisfaction and constitute a predictive
      factor for the quality of symptom treatment and palliative care.

PMID- 25998177
TI  - Normative Data and Dialectical Effects on Nasalance in Flemish Adults.
AB  - OBJECTIVE: The purpose of this study was to investigate the impact of dialect and
      gender and to obtain normative nasalance values for Flemish adults as measured
      with the Nasometer II. SUBJECTS AND METHODS: One hundred and sixty-four adult
      subjects from the five regions in Flanders corresponding to different dialects
      were included in the study. The group consisted of 71 adult men and 93 adult
      women with a mean age of 43 years and an age range between 20 and 82 years (SD
      16). Nasalance scores of connected speech using an oral, an oronasal and a nasal
      text were measured with the Nasometer II model 6450. RESULTS: The nasalance
      scores for the oral, oronasal and nasal texts are provided in this study. No
      significant differences were found across the five dialects and between men and
      women. CONCLUSION: This study provides new Flemish normative data as measured
      with the Nasometer II model 6450. The results of this study are very important
      for clinical purposes and for future Flemish studies collecting nasalance scores
      of subjects with different dialects.

PMID- 25998178
TI  - The Relationship between Retinol-Binding Protein 4 Concentrations and Gestational
      Diabetes Mellitus in Chinese Women.
AB  - BACKGROUND: This study aimed to investigate the relationship between retinol
      binding protein 4 (RBP4) and gestational diabetes mellitus (GDM). METHODS:
      Seventy-six women with and without GDM were recruited. Their blood samples were
      collected to detect RBP4, fasting plasma glucose (FPG), fasting insulin (Fins),
      triglyceride (TG), total cholesterol (TC), low-density lipoprotein, high-density
      lipoprotein (HDL) and glycosylated hemoglobin (HbA1c) levels. RESULTS: RBP4
      (21.42 +/- 3.846 vs. 39.08 +/- 8.293 MUg/ml), FPG, Fins, homeostasis model
      assessment of insulin resistance (HOMA-IR), HbA1c, and TG levels were higher,
      while HDL levels were lower in women with GDM (p < 0.01). In healthy controls,
      RBP4 concentrations were positively correlated with HOMA-IR and TG and inversely
      correlated with FPG and HDL (p < 0.05). Serum concentrations of RBP4 in women
      with GDM were inversely correlated with TC and positively correlated with
      maternal weight gain during pregnancy (p < 0.05). The ROC curve was drawn with a
      correct rate of 93.4%. CONCLUSIONS: Concentrations of serum RBP4 were
      significantly higher in women with GDM, suggesting that elevated RPB4 level may
      play a role in the pathogenesis of GDM. Meanwhile, RBP4 might be a good predictor
      of GDM. RBP4 is correlated with TG and HDL, indicating that RBP4 plays a role in
      alterations of lipid metabolism in pregnant women. (c) 2015 S. Karger AG, Basel.

PMID- 25998175
TI  - Trans-ethnic meta-analysis identifies common and rare variants associated with
      hepatocyte growth factor levels in the Multi-Ethnic Study of Atherosclerosis
      (MESA).
AB  - Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor that
      regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of
      cells, and increased serum levels of HGF have been linked to a number of clinical
      and subclinical cardiovascular disease phenotypes. However, little is currently
      known regarding which genetic factors influence HGF levels, despite evidence of
      substantial genetic contributions to HGF variation. Based upon ethnicity
      stratified single-variant association analysis and trans-ethnic meta-analysis of
      6201 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we
      discovered five statistically significant common and low-frequency variants: HGF
      missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364,
      rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also
      identified two significant ethnicity-specific gene-level associations (A1BG in
      African Americans; FASN in Chinese Americans) based upon low-frequency/rare
      variants, while meta-analysis of gene-level results identified a significant
      association for HGFAC. However, identified single-variant associations explained
      modest proportions of the total trait variation and were not significantly
      associated with coronary artery calcium or coronary heart disease. Our findings
      indicate that genetic factors influencing circulating HGF levels may be complex
      and ethnically diverse. 

PMID- 25998179
TI  - [Early prenatal interview knowledge in post-partum women: Cross-sectional study
      in 2011 in Lille (France)].
AB  - OBJECTIVES: Early prenatal interview (EPI) is one of the flagship measures of the
      2005-2007 perinatal strategy. It allows mothers to have a 45-minute interview,
      distinct from a medical consultation, promoting the expression of their
      expectations and medical, psychological or social difficulties. It should be
      routinely offered to all mothers in early pregnancy. The main objective of our
      study was to determine the proportion of women who had knowledge of Early
      prenatal interview and to profile women who knew it. Secondary objectives were to
      describe the EPI achievement rate and its terms of implementation. MATERIALS AND
      METHODS: All women who gave birth between 16 and 20 January 2011 in one of the
      ten maternity hospitals of the Lille metropolis were interviewed during their
      stay in maternity. A mixed model logistic regression was made to draw the profile
      of women with knowledge of Early prenatal interview. RESULTS: Of 311 women who
      gave birth during the study period, 270 were included in the survey. 148 patients
      (54.8 %) knew Early prenatal interview and 79 (29.3 %) had it. Women who had a
      high level of education were significantly more aware of this interview than
      those with low level of study. Other factors studied were not significantly
      related to knowledge of the EPI. CONCLUSION: While the EPI should be routinely
      offered to all pregnant women, only half of the patients who give birth had heard
      about it during their pregnancy. Women of low educational level should be more
      targeted by professional performing this interview.

PMID- 25998181
TI  - Correlations between posterior longitudinal injury and parameters of vertebral
      body damage.
AB  - BACKGROUND: The posterior longitudinal ligament (PLL) is an important structure
      of spinal stability. The loss of vertebral body height, local kyphosis (LK), and
      canal compromise may lead to spinal instability. This study determined the
      correlations between injury of the PLL and the loss of vertebrae height,
      kyphosis, and canal compromise. MATERIALS AND METHODS: A retrospective review of
      a thoracolumbar burst fracture database was conducted from January 2009 to
      December 2011. Patients were divided into an intact group and a disrupted group
      according to the status of the PLL. The loss of vertebral height, mid-sagittal
      canal diameter, and LK was measured. The anterior, middle, and posterior
      vertebral compression ratios (AVBCR, MVBCR, and PVBCR) and mid-sagittal diameter
      compression ratio (MSDCR) were calculated. RESULTS: Forty-seven patients were
      included in the study, including 25 patients in the intact group and 22 patients
      in the disrupted group. There were significant differences in the AVBCR (t = 
      3.048, P = 0.004), MVBCR (t = -2.301, P = 0.048), PVBCR (t = -2.116, P = 0.040),
      and MSDCR (t = -4.095, P = 0.000) but no difference in the LK (t = 0.408, P =
      0.686) between the two groups. There was a positive correlation between the
      injury of the PLL and the MSDCR (r = 0.428, P < 0.01), AVBCR (r = 0.372, P <
      0.01), and PVBCR (r = 0.271, P < 0.05). There was no correlation between the
      injury of the PLL and the LK and MVBCR. CONCLUSIONS: The MVBCR and LK are not
      predictive of a PLL injury. The MSDCR, AVBCR, and PVBCR were associated with a
      PLL injury.

PMID- 25998180
TI  - MicroC(3): an ex vivo microfluidic cis-coculture assay to test chemosensitivity
      and resistance of patient multiple myeloma cells.
AB  - Chemosensitivity and resistance assays (CSRAs) aim to direct therapies based upon
      ex vivo responses of patient tumor cells to chemotherapeutic drugs. However,
      successful CSRAs are yet to be developed. Here, we exposed primary CD138(+)
      multiple myeloma (MM) cells to bortezomib, a clinical proteasome inhibitor, in
      microfluidic-cis-coculture (MicroC(3)) incorporating the patient's own CD138(-)
      tumor-companion mononuclear cells to integrate some of the patients' own tumor
      microenvironment components in the CSRA design. Statistical clustering techniques
      segregated MicroC(3) responses into two groups which correctly identified all
      seventeen patients as either clinically responsive or non-responsive to
      bortezomib-containing therapies. In contrast, when the same patient MM samples
      were analyzed in the absence of the CD138(-) cells (monoculture), the tumor cell
      responses did not segregate into clinical response clusters. Thus, MicroC(3)
      identified bortezomib-therapy MM patient responses making it a viable CSRA
      candidate toward enabling personalized therapy. 

PMID- 25998182
TI  - Rhodiola crenulata inhibits Wnt/beta-catenin signaling in glioblastoma.
AB  - BACKGROUND: Rhodiola crenulata is a perennial plant that grows in the high
      altitudes of Eastern Europe and Asia. R crenulata has been used for many years in
      Eastern traditional medicine for a variety of medicinal purposes and it has been
      shown to elicit antineoplastic effects. The purpose of this study is to determine
      if R crenulata extract exhibits antitumor properties on glioblastoma multiforme
      (GBM), the most common and aggressive primary brain tumor. MATERIALS AND METHODS:
      Human U87 GBM cells were treated with 200 MUg/mL of R crenulata or vehicle
      control. Cell proliferation was measured via MTS assay and clonogenic assay. The
      expressions of glial fibrillary acidic protein, a protein marker of
      differentiation, E-cadherin, and non-phospho active beta-catenin were measured
      with immunocytochemistry. Neurosphere assay was performed in low attachment
      plates. Activity of the Wnt/beta-catenin transcriptional activation was assessed
      via a dual-luciferase assay. RESULTS: MTS and clonogenicity assays revealed a
      decrease in proliferation with R crenulata therapy with an increased sensitivity
      to radiation. Immunocytochemistry revealed that R crenulata induced glial
      fibrillary acidic protein and E-cadherin expression suggestive of a more
      differentiated state. In agreement with the change in differentiation neurosphere
      formation was decreased upon treatment with R crenulata. beta-Catenin dual
      reporter assay revealed a decrease in Wnt promoter activity after treatment with
      R crenulata; this was supported by a decrease in nuclear localization of beta
      catenin. CONCLUSIONS: Treatment with R crenulata extract effectively suppresses
      proliferation, stimulates differentiation, and eliminates tumorsphere formation
      of GBM cells in vitro. The observed effects are associated with inhibition of
      Wnt/beta-catenin signaling pathway.

PMID- 25998183
TI  - Deep vein thrombosis screening and risk factors in a high-risk trauma population.
AB  - BACKGROUND: Trauma patients requiring acute inpatient rehabilitation are
      significantly injured, with increased risk for deep vein thrombosis (DVT). We
      evaluated routine screening for occult DVT in such patients, and analyzed DVT
      risk factors. MATERIALS AND METHODS: Data from level I trauma center patients
      discharged to a single acute rehabilitation center (ARC) from 2007-2011 were
      retrospectively reviewed. Routine lower extremity duplex was performed on ARC
      admission. Follow-up data were collected for patients with occult DVT (ARC DVT).
      DVT predictors were evaluated using logistic regression. RESULTS: Of 622
      patients, 534 (86%) had screening duplex; 26 (4.8%) had an ARC DVT. A majority of
      442 patients (71%) received enoxaparin prophylaxis in hospital, for a median 64%
      of hospital days. Of ARC DVT patients, 17 received full anticoagulation and 16
      received vena cava filters. Thirty-seven patients had DVT diagnosed in the
      hospital (hospital DVT) before discharge to ARC. Hospital DVT and ARC DVT groups
      were comparable except shorter median hospital length of stay and lower head
      abbreviated injury scale in ARC DVT patients. On multivariate analysis, increased
      intensive care unit length of stay, age >65 y, a lower percentage of hospital
      days receiving chemoprophylaxis, and delayed initiation of chemoprophylaxis were
      significantly predictive of DVT after adjustment for sex, mechanism, injury
      severity score, and admission systolic blood pressure. Presence of pelvic
      fractures and ages 50-65 y also posed an increased risk. CONCLUSIONS: The
      incidence of occult DVT on ARC admission is low in trauma patients. Several risk
      factors for DVT in the trauma ARC population were identified. Nonselective
      screening of all trauma patients on admission to ARC is not supported by this
      analysis.

PMID- 25998184
TI  - Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer
      by activating JNK signaling.
AB  - Dual-specificity phosphatase 9 (DUSP9) is a strong negative regulator of
      transcription factor activating kinases (ERK, JNK and p38) in the mitogen
      activated protein kinase (MAPK) pathways. The aim of this study was to examine
      the CpG island methylation status of DUSP9 using bisulfite sequencing PCR (BSP)
      in gastric cancer (GC). The investigation was conducted on 30 clinical GC samples
      and selected corresponding tumor-free normal gastric mucosa tissues, using BSP
      for the determination of the promoter methylation status. The methylation status
      of the tumor samples was compared to the corresponding tumor-free samples. DUSP9
      was silenced by promoter region hypermethylation and G2/M phase arrest was
      induced by DUSP9 in the MKN-1 GC cell line. MKN-1 proliferation was suppressed by
      DUSP9 by inhibiting c-Jun, which was induced by JNK signaling. The expression
      levels of CCND1, c-Jun, CDK4 and CDK6 were upregulated while p21 was
      downregulated by DUSP9 in MKN-1 cells. However, DUSP9-induced resulted in the
      regulation of the levels of cycle-related molecules, whivh were inhibited when
      the JNK inhibitor SP600125 was added. In conclusion, DUSP9 was frequently
      methylated in human GC and the expression of DUSP9 is silenced by promoter region
      hypermethylation. The results of this study, combined with previous studies,
      suggested that therapeutic intervention to increase the expression or activity of
      DUSP9 may enable the activation of anti-proliferation signals in malignant cells.

PMID- 25998185
TI  - Presence of hydroxy ethyl starch increases the false positive anti-HIV test
      results in cord blood samples.

PMID- 25998187
TI  - Ca2+ Dependence of Synaptic Vesicle Endocytosis.
AB  - Ca(2+)-dependent synaptic vesicle recycling is essential for structural
      homeostasis of synapses and maintenance of neurotransmission. Although, the
      executive role of intrasynaptic Ca(2+) transients in synaptic vesicle exocytosis
      is well established, identifying the exact role of Ca(2+) in endocytosis has been
      difficult. In some studies, Ca(2+) has been suggested as an essential trigger
      required to initiate synaptic vesicle retrieval, whereas others manipulating
      synaptic Ca(2+) concentrations reported a modulatory role for Ca(2+) leading to
      inhibition or acceleration of endocytosis. Molecular studies of synaptic vesicle
      endocytosis, on the other hand, have consistently focused on the roles of Ca(2+)
      calmodulin dependent phosphatase calcineurin and synaptic vesicle protein
      synaptotagmin as potential Ca(2+) sensors for endocytosis. Most studies probing
      the role of Ca(2+) in endocytosis have relied on measurements of synaptic vesicle
      retrieval after strong stimulation. Strong stimulation paradigms elicit fusion
      and retrieval of multiple synaptic vesicles and therefore can be affected by
      several factors besides the kinetics and duration of Ca(2+) signals that include
      the number of exocytosed vesicles and accumulation of released neurotransmitters
      thus altering fusion and retrieval processes indirectly via retrograde signaling.
      Studies monitoring single synaptic vesicle endocytosis may help resolve this
      conundrum as in these settings the impact of Ca(2+) on synaptic fusion
      probability can be uncoupled from its putative role on synaptic vesicle
      retrieval. Future experiments using these single vesicle approaches will help
      dissect the specific role(s) of Ca(2+) and its sensors in synaptic vesicle
      endocytosis.

PMID- 25998186
TI  - Pediatric Residents' Knowledge and Comfort With Oral Health Bright Futures
      Concepts: A CORNET Study.
AB  - OBJECTIVE: Training residents in oral health helps eliminate disparities and
      improves access. The American Academy of Pediatrics Bright Futures Guidelines
      curriculum is used as a training guide. We assessed knowledge, confidence, and
      perceived barriers to incorporating Bright Futures oral health concepts into well
      child care for children below 3 years in a national sample of pediatric
      residents. METHODS: A sample of postgraduate year 1 and 2 residents from CORNET
      sites completed demographic, Bright Futures oral health concepts confidence and
      knowledge cross-sectional surveys before any intervention. Measures were tested
      for reliability using Cronbach's alpha coefficient. RESULTS: One hundred sixty
      three residents from 28 CORNET sites completed the surveys. One third reported no
      prior training in oral health. Time (42%) and knowledge (33%) led the perceived
      barriers to addressing these concepts in well visits. Although 63% rated their
      confidence as excellent in identifying tooth decay risk factors, a significant
      percentage rated their oral health risk assessment skills as poor or neutral
      (64%) and identifying caries at examination (53%). Only 49% conveyed oral health
      messages during encounters and 80% correctly scored 75% or higher on knowledge
      questions. CONCLUSIONS: This cross-sectional study shows that residents from a
      wide geographic range have high self-reported oral health knowledge but low
      perceived skills and competency in clinical implementation. Lack of time and
      knowledge in identifying caries led the perceived barriers. Barriers are
      addressed by implementing oral health curricula that promote competence and skill
      development. This study helps programs effectively implement Bright Futures
      concepts to train graduates to incorporate oral health in well visits.

PMID- 25998188
TI  - Health professionals' and patients' perspectives on pelvic floor muscle training
      adherence-2011 ICS State-of-the-Science Seminar research paper IV of IV.
AB  - AIMS: There is scant information on pelvic floor muscle training (PFMT) adherence
      barriers and facilitators. A web-based survey was conducted (1) to investigate
      whether responses from health professionals and the public broadly reflected
      findings in the literature, (2) if responses differed between the two groups, and
      (3) to identify new research directions. METHODS: Health professional and public
      surveys were posted on the ICS website. PFMT adherence barriers and facilitators
      were divided into four categories: physical/condition, patient, therapy, and
      social-economic. Responses were analyzed using descriptive statistics from
      quantitative data and thematic data analysis for qualitative data. RESULTS: Five
      hundred and fifteen health professionals and 51 public respondents participated.
      Both cohorts felt "patient-related factors" constituted the most important
      adherence barrier, but differed in their rankings of short- and long-term
      barriers. Health professionals rated "patient-related" and the public "therapy
      related" factors as the most important adherence facilitator. Both ranked
      "perception of PFMT benefit" as the most important long-term facilitator.
      Contrary to published findings, symptom severity was not ranked highly. Neither
      cohort felt the barriers nor facilitators differed according to PFM condition
      (urinary/faecal incontinence, pelvic organ prolapse, pelvic pain); however, a
      large number of health professionals felt differences existed across age, gender,
      and ethnicity. Half of respondents in both cohorts felt research barriers and
      facilitators differed from those in clinical practice. CONCLUSIONS: An emphasis
      on "patient-related" factors, ahead of "condition-specific" and "therapy
      related," affecting PFMT adherence barriers was evident. Health professionals
      need to be aware of the importance of long-term patient perception of PFMT
      benefits and consider enabling strategies.

PMID- 25998189
TI  - Computational Models of the Representation of Bangla Compound Words in the Mental
      Lexicon.
AB  - In this paper we aim to model the organization and processing of Bangla compound
      words in the mental lexicon. Our objective is to determine whether the mental
      lexicon access a Bangla compound word as a whole or decomposes the whole word
      into its constituent morphemes and then recognize them accordingly. To address
      this issue, we adopted two different strategies. First, we conduct a cross-modal
      priming experiment over a number of native speakers. Analysis of reaction time
      (RT) and error rates indicates that in general, Bangla compound words are
      accessed via partial decomposition process. That is some word follows full
      listing mode of representation and some words follow the decomposition route of
      representation. Next, based on the collected RT data we have developed a
      computational model that can explain the processing phenomena of the access and
      representation of Bangla compound words. In order to achieve this, we first
      explored the individual roles of head word position, morphological complexity,
      orthographic transparency and semantic compositionality between the constituents
      and the whole compound word. Accordingly, we have developed a complexity based
      model by combining these features together. To a large extent we have
      successfully explained the possible processing phenomena of most of the Bangla
      compound words. Our proposed model shows an accuracy of around 83 %. 

PMID- 25998190
TI  - Curcumin Modulates Macrophage Polarization Through the Inhibition of the Toll
      Like Receptor 4 Expression and its Signaling Pathways.
AB  - BACKGROUND: Curcumin, the active ingredient in curcuma rhizomes, has a wide range
      of therapeutic effects. However, its atheroprotective activity in human acute
      monocytic leukemia THP-1 cells remains unclear. We investigated the activity and
      molecular mechanism of action of curcumin in polarized macrophages. METHODS:
      Phorbol myristate acetate (PMA)-treated THP-1 cells were differentiated to
      macrophages, which were further polarized to M1 cells by lipopolysaccharide (LPS;
      1 ug/ml) and interferon (IFN)-gamma (20 ng/ml) and treated with varying curcumin
      concentrations. [3H]thymidine (3H-TdR) incorporation assays were utilized to
      measure curcumin-induced growth inhibition. The expression of tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL-6), and IL-12B (p40) were measured by
      quantitative real-time polymerase chain reaction (PCR) and enzyme-linked
      immunosorbent assay (ELISA). Macrophage polarization and its mechanism were
      evaluated by flow cytometry and western blot. Additionally, toll-like receptor 4
      (TLR4) small interfering RNA and mitogen-activated protein kinase (MAPK)
      inhibitors were used to further confirm the molecular mechanism of curcumin on
      macrophage polarization. RESULTS: Curcumin dose-dependently inhibited M1
      macrophage polarization and the production of TNF-alpha, IL-6, and IL-12B (p40).
      It also decreased TLR4 expression, which regulates M1 macrophage polarization.
      Furthermore, curcumin significantly inhibited the phosphorylation of ERK, JNK,
      p38, and nuclear factor (NF)-kappaB. In contrast, SiTLR4 in combination with p
      JNK, p-ERK, and p-p38 inhibition reduced the effect of curcumin on polarization.
      CONCLUSIONS: Curcumin can modulate macrophage polarization through TLR4-mediated
      signaling pathway inhibition, indicating that its effect on macrophage
      polarization is related to its anti-inflammatory and atheroprotective effects.
      Our data suggest that curcumin could be used as a therapeutic agent in
      atherosclerosis.

PMID- 25998191
TI  - Genomic tumor evolution of breast cancer.
AB  - Owing to recent technical development of comprehensive genome-wide analysis such
      as next generation sequencing, deep biological insights of breast cancer have
      been revealed. Information of genomic mutations and rearrangements in patients'
      tumors is indispensable to understand the mechanism in carcinogenesis,
      progression, metastasis, and resistance to systemic treatment of breast cancer.
      To date, comprehensive genomic analyses illustrate not only base substitution
      patterns and lists of driver mutations and key rearrangements, but also a manner
      of tumor evolution. Breast cancer genome is dynamically changing and evolving
      during cancer development course from non-invasive disease via invasive primary
      tumor to metastatic tumor, and during treatment exposure. The accumulation
      pattern of base substitution and genomic rearrangement looks gradual and
      punctuated, respectively, in analogy with contrasting theories for evolution
      manner of species, Darwin's phyletic gradualism, and Eldredge and Gould's
      "punctuated equilibrium". Liquid biopsy is a non-invasive method to detect the
      genomic evolution of breast cancer. Genomic mutation patterns in circulating
      tumor cells and circulating cell-free tumor DNA represent those of tumors
      existing in patient body. Liquid biopsy methods are now under development for
      future application to clinical practice of cancer treatment. In this article,
      latest knowledge regarding breast cancer genome, especially in terms of 'tumor
      evolution', is summarized. 

PMID- 25998192
TI  - Guidance for infection prevention and healthcare epidemiology programs:
      healthcare epidemiologist skills and competencies.

PMID- 25998194
TI  - Is it time to leave the avoidance of rupture of membranes for women infected with
      HIV and receiving cART in the past?

PMID- 25998193
TI  - Knot Security of 5 Metric (USP 2) Sutures: Influence of Knotting Technique,
      Suture Material, and Incubation Time for 14 and 28 Days in Phosphate Buffered
      Saline and Inflamed Equine Peritoneal Fluid.
AB  - OBJECTIVES: To evaluate knot security for 3 knot types created in 3 commonly used
      5 metric suture materials incubated in physiological and pathological fluids.
      STUDY DESIGN: In vitro mechanical study. SAMPLE POPULATION: Knotted suture loops
      (n = 5/group). METHODS: Loops of 3 different suture materials (glycolide/lactide
      copolymer; polyglactin 910; polydioxanone) were created around a 20 mm rod using
      3 knot types (square [SQ], surgeon's [SK], and triple knot [TK]) and were tested
      to failure in distraction (6 mm/min) after tying (day 0) and after being
      incubated for 14 and 28 days in phosphate buffered saline (PBS) or inflamed
      peritoneal fluid. Failure load (N) and mode were recorded and compared. RESULTS:
      For polydioxanone, significant differences in force to knot failure were found
      between SQ and SK/TK but not between SK and TK. The force required to break all
      constructs increased after incubation in phosphate buffered saline (PBS). With
      glycolide/lactide copolymer no differences in force to knot failure were
      observed. With polyglactin 910, a significant difference between SQ and TK was
      observed, which was not seen between the other knot types. Incubation in inflamed
      peritoneal fluid caused a larger and more rapid decrease in force required to
      cause knot failure than incubation in PBS. CONCLUSIONS: Mechanical properties of
      suture materials have significant effects on knot security. For polydioxanone, SQ
      is insufficient to create a secure knot. Additional wraps above a SK confer extra
      stability in some materials, but this increase may not be clinically relevant or
      justifiable. Glycolide/lactide copolymer had excellent knot security.

PMID- 25998195
TI  - Centrosome nucleates numerous ephemeral microtubules and only few of them
      participate in the radial array.
AB  - It is generally accepted that long microtubules (MTs) grow from the centrosome
      with their minus ends anchored there and plus ends directed towards cell
      membrane. However, recent findings show this scheme to be an oversimplification.
      To further analyze the relationship between the centrosome and the MT array we
      undertook a detailed study on the MTs growing from the centrosome after
      microinjection of Cy3 labeled tubulin and transfection of cells with EB1-GFP. To
      evaluate MTs around the centrosome two approaches were used: path photobleaching
      across the centrosome area (Komarova et al., ) and sequential image subtraction
      analysis (Vorobjev et al., ). We show that about 50% of MTs had been nucleated at
      the centrosome are short-living: their mean length was 1.8 +/- 0.8 MUm and their
      life span - 7 +/- 2 s. MTs initiated from the centrosome also rarely reach cell
      margin, since their elongation was limited and growth after shortening (rescue)
      was rare. After initial growth all MTs associated with the centrosome converted
      to pause or shortening. After pause MTs associated with the centrosome mainly
      depolymerized via the plus end shortening. Stability of the minus ends of
      cytoplasmic MTs was the same as for centrosomal ones. We conclude that in
      fibroblasts (1) the default behavior of free MTs in the cell interior is biased
      dynamic instability (i.e., random walk of the plus ends with significant positive
      drift); (2) MTs born at the centrosome show "dynamic instability" type behavior
      with no boundary; and (3) that the extended radial array is formed predominantly
      by MTs not associated with the centrosome.

PMID- 25998196
TI  - Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by
      inhibiting protein ubiquitination.
AB  - NEW FINDINGS: What is the central question of this study? We sought to examine
      whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by
      inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress.
      What is the main finding and its importance? We found that curcumin ameliorated
      skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting
      protein ubiquitination without affecting protein synthesis. This favourable
      effect of curcumin was possibly due to the inhibition of inflammatory cytokines
      and oxidative stress. Curcumin may be beneficial for the treatment of muscle
      atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients
      with diabetes mellitus (DM), especially in type 1 DM, which is associated with
      chronic inflammation. Curcumin, the active ingredient of turmeric, has various
      biological actions, including anti-inflammatory and antioxidant properties. We
      hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with
      streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with
      streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each
      group of mice was randomly subdivided into two groups of 10 mice each and fed a
      diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were
      significant decreases in body weight, skeletal muscle weight and cellular cross
      sectional area of the skeletal muscle in DM mice compared with control mice, and
      these changes were significantly attenuated in DM+Curcumin mice without affecting
      plasma glucose and insulin concentrations. Ubiquitination of protein was
      increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene
      expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were
      increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor
      kappaB activation, concentrations of the inflammatory cytokines tumour necrosis
      factor-alpha and interleukin-1beta and oxidative stress were increased in the
      skeletal muscle from DM mice and inhibited in DM+Curcumin mice. Curcumin
      ameliorated skeletal muscle atrophy in DM mice by inhibiting protein
      ubiquitination, inflammatory cytokines and oxidative stress. Curcumin may be
      beneficial for the treatment of muscle atrophy in type 1 DM.

PMID- 25998197
TI  - Extended curettage and adjuvant therapy for benign tumors of the talus.
AB  - PURPOSE: Benign tumors of the talus are rare, and their management is
      controversial. Recent efforts have extended the safety margin of intralesional
      excision and curettage by chemical and physical means. Cryotherapy as adjuvant
      therapy is associated with risks of local wound and bony complications (delayed
      healing, potential for pathological fractures). METHODS: We retrospectively
      reviewed six cases of benign talar tumors (three giant cell tumors, two
      aneurysmal bone cysts, one osteoblastoma) treated by extended curettage and
      adjuvant cryotherapy. Talar bone stock was restored by bone grafting the residual
      cavity with fibular strut grafts and/or cancellous bone grafts. Patients were
      followed for a mean of 40 months. RESULTS: At latest follow-up, each patient had
      a mobile painless ankle and good functional outcome. No patient experienced
      recurrence or complications related to cryotherapy. CONCLUSIONS: Intralesional
      extended curettage with bone grafting and cryotherapy is a successful, safe, and
      efficient treatment of benign tumors of the talus.

PMID- 25998198
TI  - T-Cell Activation and Malnutrition Adversely Impact on Endothelial Progenitor
      Cell Mobilization in Patients on Extracorporeal Maintenance Dialysis Therapy.
AB  - BACKGROUND: The number of circulating endothelial progenitor cells (EPCs)
      decreases on account of chronic kidney disease (CKD). METHODS: Twenty patients
      were enrolled in this prospective and randomised study in two parallel arms:
      conventional haemodialysis versus online haemodiafiltration. EPCs number and T
      cell activation were analysed at baseline and monthly during a 4-month period of
      follow-up. RESULTS: CD38(bright) and HLA-DR+ expression among CD8 memory T cells
      were negatively associated with both CD34+ (r = -0.70, p = 0.0006) and CD34+
      CD133+ (r = -0.62, p = 0.004) cell numbers. Conversely, a positive correlation
      was observed between CD34+ and CD34+ CD133+ cells with transferrin (r = 0.75, p =
      0.0001 and r = 0.47, p = 0.04, respectively), and CD34+ CD133+ cells with
      transthyretin (r = 0.51, p = 0.02). No significant association was observed
      between dialysis modality and the evolution of the EPC number. CONCLUSIONS:
      Chronic T-cell activation may be a component of the malnutrition inflammation
      complex syndrome that adversely influences EPC mobilization in CKD patients.

PMID- 25998199
TI  - Structure determination of two new bisabolane-type sesquiterpenes from the
      rhizomes of Curcuma longa by NMR spectroscopy.

PMID- 25998200
TI  - Reversible pH-controlled switching of an artificial antioxidant selenoenzyme
      based on pseudorotaxane formation and dissociation.
AB  - A pH-responsive artificial selenoenzyme was constructed by reversible binding
      between organoselenium compound a1 nd CB[6] to form a pseudorotaxane-based
      molecular switch in response to pH stimuli. The glutathione peroxidase (GPx)
      activity of the artificial selenoenzyme can be switched on/off in a mild and body
      suitable environment between pH = 7 and pH = 6.

PMID- 25998201
TI  - Everybody has Brugada syndrome until proven otherwise?

PMID- 25998202
TI  - The significance of muscle echo intensity on ultrasound for focal neuropathy: The
      median- to ulnar-innervated muscle echo intensity ratio in carpal tunnel
      syndrome.
AB  - OBJECTIVE: The objective of this study was to investigate the usefulness of
      muscle ultrasound for evaluating muscle changes caused by denervation in carpal
      tunnel syndrome (CTS), which is a focal neuropathy. METHODS: The mean and
      standard deviation (SD) of echo intensity (EI) in the thenar and hypothenar
      muscles were calculated in 35 patients with CTS and 11 healthy subjects. Patients
      were assigned to three subgroups based on CTS severity as determined by
      electrodiagnostic tests. The ratio of thenar muscle pixel brightness to
      hypothenar muscle pixel brightness was used in statistical analyses. The ratio of
      mean pixel brightness was termed the EI ratio, and the ratio of the SD of pixel
      brightness was termed the inhomogeneity ratio. RESULTS: Both the EI ratio and the
      inhomogeneity ratio were significantly higher in the patient group than in the
      control group. In a comparison of the three patient subgroups, the severe group
      showed significant differences in both the EI and inhomogeneity ratios compared
      to the other two groups. Subjects with denervation potential in the abductor
      pollicis brevis (APB) had higher EI and inhomogeneity ratios than subjects
      without denervation potential in the APB. CONCLUSION: The EI ratio and
      inhomogeneity ratio are useful variables with which to evaluate disease severity
      and the presence of denervation in patients with CTS. SIGNIFICANCE: Muscle
      ultrasound has clinical significance in the detection of muscle changes that
      result from neuropathy.

PMID- 25998203
TI  - The identification of distinct high-frequency oscillations during spikes
      delineates the seizure onset zone better than high-frequency spectral power
      changes.
AB  - OBJECTIVE: Interictal high-frequency oscillations (HFOs, 80-500Hz) can predict
      the seizure onset zone (SOZ), but visual detection of HFOs is time consuming.
      Time-frequency analysis can reveal large high-frequency (HF) power changes (80
      500Hz) associated with inter-ictal spikes. The present study determines how well
      the rate of HFOs and spike-related HF power changes were co-localized with SOZ.
      METHODS: We analyzed 583 channels (68 in the SOZ) sampled from 14 patients who
      underwent intracranial EEG recording. We determined if the rate of visually
      marked HFOs and spike-related HF power changes differed between SOZ and non-SOZ.
      RESULTS: Significantly higher rates of HFOs were found in SOZ. The degree of
      spike-related HF power augmentation failed to differ between SOZ and non-SOZ,
      whereas that of post-spike HF power attenuation was significantly more severe in
      SOZ compared to in non-SOZ. Regions showing HFOs and large spike-related HF
      changes showed a partial overlap in distribution in 7/14 patients. CONCLUSIONS:
      Strong HF augmentation during spikes and high HFO rates occurred over different
      brain locations. The rate of HFOs showed the best performance in identifying SOZ.
      Post-spike HF power attenuation may represent increased inhibition in these
      channels and should be investigated further. SIGNIFICANCE: Strong HF power
      changes during spikes and HFOs per se seem to reflect distinct phenomena.

PMID- 25998204
TI  - Relationships between interictal epileptic spikes and ripples in surface EEG.
AB  - OBJECTIVE: Ripples (80-250Hz) have been shown to be a more specific biomarker for
      the epileptogenic zone than epileptic spikes in intracranial EEG and even surface
      EEG. Ripples often co-occur with spikes. We investigated the spatiotemporal
      relation between spikes and ripples, and differences between spikes that do and
      do not co-occur with ripples. METHODS: We marked 50 time points with spikes in
      bipolar surface EEG during NREM sleep in patients with focal or multifocal
      epilepsy. We marked ripples that occurred with spikes and calculated parameters
      relating spikes and ripples: the duration, amplitude and slope of spikes, the
      timing of the start of ripples and spikes and the proportion of overlap. RESULTS:
      In total 219 ripples and 5995 individual spikes were marked in 31 patients.
      Spikes with ripples were on average shorter, had higher amplitude and higher
      slope than spikes without ripples. 64% of ripples started before spikes started.
      Spikes occurred on 13 (5-26) channels per patient, and ripples on 3 (0-14)
      channels, which were also spike channels. CONCLUSION: Ripples precede rather than
      follow spikes, so ripples are unlikely to result from spikes. SIGNIFICANCE:
      Ripples and spikes seem not one-on-one coupled, but certain states of the brain
      can accommodate both.

PMID- 25998205
TI  - Multiple sessions of transcranial direct current stimulation and upper extremity
      rehabilitation in stroke: A review and meta-analysis.
AB  - OBJECTIVE: To systematically review the methodology in particular treatment
      options and outcomes and the effect of multiple sessions of transcranial direct
      current stimulation (tDCS) with rehabilitation programmes for upper extremity
      recovery post stroke. METHODS: A search was conducted for randomised controlled
      trials involving tDCS and rehabilitation for the upper extremity in stroke.
      Quality of included studies was analysed using the Modified Downs and Black form.
      The extent of, and effect of variation in treatment parameters such as anodal,
      cathodal and bi-hemispheric tDCS on upper extremity outcome measures of
      impairment and activity were analysed using meta-analysis. RESULTS: Nine studies
      (371 participants with acute, sub-acute and chronic stroke) were included.
      Different methodologies of tDCS and upper extremity intervention, outcome
      measures and timing of assessments were identified. Real tDCS combined with
      rehabilitation had a small non-significant effect of +0.11 (p=0.44) and +0.24
      (p=0.11) on upper extremity impairments and activities at post-intervention
      respectively. CONCLUSION: Various tDCS methods have been used in stroke
      rehabilitation. The evidence so far is not statistically significant, but is
      suggestive of, at best, a small beneficial effect on upper extremity impairment.
      SIGNIFICANCE: Future research should focus on which patients and rehabilitation
      programmes are likely to respond to different tDCS regimes.

PMID- 25998206
TI  - Effects of milnacipran on clinical pain and hyperalgesia of patients with
      fibromyalgia: results of a 6-week randomized controlled trial.
AB  - Milnacipran is a serotonin-norepinephrine reuptake inhibitor that was approved by
      the U.S. Food and Drug Administration as effective therapy for fibromyalgia (FM)
      symptoms. However, its analgesic mechanism of action is not well understood. We
      hypothesized that improvement of mechanical and heat hyperalgesia would be a
      critical component of overall milnacipran efficacy in FM. We used a novel
      quantitative sensory testing protocol for assessment of mechanical and heat pain
      sensitivity that can be used for testing of peripheral and central pain
      mechanisms and their impact on clinical pain over time. We applied tonic
      mechanical and heat pain stimuli to 46 patients with FM during a randomized
      controlled trial with either 50 mg milnacipran (n = 23) or placebo (n = 23) twice
      daily over 6 weeks. During this trial, mean clinical pain (standard deviation)
      was evaluated daily, and mechanical and heat pain sensitivity every 2 weeks. At
      study entry, clinical pain was 5.0 (1.8) and 5.5 (1.8) visual analog scale units
      for patients with FM randomized to placebo and milnacipran, respectively (P >
      .05). Over 6 weeks, clinical pain of patients with FM significantly declined by
      15%, but this improvement was not statistically different between milnacipran and
      placebo. However, repeated measures of mechanical and heat pain sensitivity
      reliably predicted up to 80% of the variance in clinical FM pain at every time
      point. Clinical pain and mechanical/heat pain sensitivity of patients with FM
      steadily declined during this trial, but the effects of milnacipran were not
      found to be superior to placebo. Repeated measures of mechanical/heat
      hyperalgesia reliably predicted large amounts of the variance in clinical pain
      across all participants, indicating their relevance for FM pain. PERSPECTIVE:
      Although clinical pain and hyperalgesia decreased during this 6-week trial, the
      efficacy of milnacipran was not superior to placebo. The high correlations
      between clinical pain and hyperalgesia ratings at every time point seem to
      emphasize the relevant contributions of mechanical and heat hyperalgesia to
      clinical FM pain.

PMID- 25998207
TI  - Cross-cultural examination of the structure of the Revised American Pain Society
      Patient Outcome Questionnaire (APS-POQ-R).
AB  - This study investigated the cross-cultural factor stability and internal
      consistency of the Revised American Pain Society Patient Outcome Questionnaire
      (APS-POQ-R), a measure of the quality of postoperative pain management used
      internationally. We conducted exploratory factor analysis (EFA) of APS-POQ-R data
      from 2 point prevalence studies comprising 268 and 311 surveys of Danish and
      Australian medical-surgical patients, respectively. Parallel analysis indicated 4
      and 3-factor solutions for Danish and Australian patients, respectively, which
      accounted for 58.1% and 52.9% of variance. Internal consistency was
      unsatisfactory among both Danish (Cronbach alpha = .54) and Australian (Cronbach
      alpha = .63) cohorts. There was a high degree of between-group similarity in item
      factor loadings of variables coded as "pain experience," but not "pain
      management." This finding reflected cross-cultural differences in ratings of
      treatment satisfaction. For Danish patients, satisfaction was associated with the
      degree of pain severity and activity interference, whereas for Australian
      patients, satisfaction was associated with their perceived ability to participate
      in treatment. To facilitate further cross-cultural comparison, we compared our
      findings with past research conducted in the United States and Iceland. EFA
      supported the construct validity of the APS-POQ-R as a measure of "pain
      experience" but indicated that items measuring "pain management" may vary cross
      culturally. Findings highlighted the need for further validation of the APS-POQ-R
      internationally. PERSPECTIVE: This study revealed the APS-POQ-R as a valid
      measure of postoperative pain experience for Danish and Australian patients.
      Measures of patients' perception of pain management were not robust to group
      differences in treatment expectations and demonstrated cross-cultural
      instability. Results highlighted the difficulties in establishing stable cross
      cultural, cross-population subscales for the APS-POQ-R.

PMID- 25998208
TI  - Management of cerebral cavernous malformations in the pediatric population: a
      literature review and case illustrations.
AB  - Cavernous malformations (CM) are vascular malformations of the central nervous
      system that may occur in the brain and spinal cord. They are one of the four
      major types of vascular malformations that also includes developmental venous
      anomalies (DVA)s, arteriovenous malformations (AVMs), and capillary
      telangiectasias. CMs are a common vascular malformation, and 25% of them occur in
      the pediatric age group. They can present with acute or chronic symptoms
      including headache, neurologic deficits secondary to hemorrhage, mass effect, or
      epilepsy. This review will focus on the neurosurgical management of intracranial
      cavernous malformations in children. Pediatric CMs have special considerations
      different from CM that occur in the adult population which are highlighted
      throughout this review. Characteristics specific to pediatric CM epidemiology,
      genetics, presentation, pathology, location, size, epilepsy, and management will
      be discussed. Specific considerations must be entertained with the diagnosis of
      pediatric CM in that management needs to include consideration of the lifetime
      risk of hemorrhage, as well as the possibility of development of epilepsy. If in
      an accessible location, most cavernomas should be surgically removed in a timely
      fashion to provide lifelong cure for pediatric patients. The review closes with
      the discussion of two interesting cavernous malformation cases occurring in a 12
      year old male and a 12-year old female that exhibit many of the important aspects
      specific to the management of a pediatric patient with CM, highlighting the
      importance of a multidisciplinary approach to treatment. 

PMID- 25998210
TI  - Modeling neural activity with cumulative damage distributions.
AB  - Neurons transmit information as action potentials or spikes. Due to the inherent
      randomness of the inter-spike intervals (ISIs), probabilistic models are often
      used for their description. Cumulative damage (CD) distributions are a family of
      probabilistic models that has been widely considered for describing time-related
      cumulative processes. This family allows us to consider certain deterministic
      principles for modeling ISIs from a probabilistic viewpoint and to link its
      parameters to values with biological interpretation. The CD family includes the
      Birnbaum-Saunders and inverse Gaussian distributions, which possess distinctive
      properties and theoretical arguments useful for ISI description. We expand the
      use of CD distributions to the modeling of neural spiking behavior, mainly by
      testing the suitability of the Birnbaum-Saunders distribution, which has not been
      studied in the setting of neural activity. We validate this expansion with
      original experimental and simulated electrophysiological data. 

PMID- 25998209
TI  - Phosphorylation of the nuclear receptor corepressor 1 by protein kinase B
      switches its corepressor targets in the liver in mice.
AB  - Nuclear receptor corepressor 1 (NCoR1) is a transcriptional coregulator that has
      wide-ranging effects on gene expression patterns. In the liver, NCoR1 represses
      lipid synthesis in the fasting state, whereas it inhibits activation of
      peroxisome proliferator-activated receptor alpha (PPARalpha) upon feeding,
      thereby blunting ketogenesis. Here, we show that insulin by activation of protein
      kinase B induces phosphorylation of NCoR1 on serine 1460, which selectively
      favors its interaction with PPARalpha and estrogen-related receptor alpha
      (ERRalpha) over liver X receptor alpha (LXRalpha). Phosphorylation of NCoR1 on
      S1460 selectively derepresses LXRalpha target genes, resulting in increased
      lipogenesis, whereas, at the same time, it inhibits PPARalpha and ERRalpha
      targets, thereby attenuating oxidative metabolism in the liver. Phosphorylation
      gated differential recruitment of NCoR1 to different nuclear receptors explains
      the apparent paradox that liver-specific deletion of NCoR1 concurrently induces
      both lipogenesis and oxidative metabolism owing to a global derepression of
      LXRalpha, PPARalpha, and ERRalpha activity. CONCLUSION: Phosphorylation-mediated
      recruitment switch of NCoR1 between nuclear receptor subsets provides a mechanism
      by which corepressors can selectively modulate liver energy metabolism during the
      fasting-feeding transition.

PMID- 25998212
TI  - Pharmacokinetics and Safety Profile of DA-3803, a Proposed Biosimilar of
      Recombinant Human Chorionic Gonadotropin, in Healthy Subjects.
AB  - BACKGROUND AND OBJECTIVE: DA-3803 is a proposed biosimilar of recombinant human
      chorionic gonadotropin (r-hCG), which is a therapeutic protein used to treat
      infertility. We compared the pharmacokinetics and safety profiles of DA-3803
      (test) with those of a conventional formulation (Ovidrel((r)), reference).
      METHODS: A single-blind, randomized, single-dose, two-period, two-sequence,
      crossover study was conducted in 32 healthy subjects. In each period, 250 MUg of
      r-hCG of the test or reference formulation was administered subcutaneously with a
      3-week washout period. Serial blood samples were obtained for pharmacokinetic
      analysis and blood levels of human chorionic gonadotropin (hCG) were determined.
      The geometric mean ratios (GMRs) with 90 % confidence intervals (CIs) for the
      maximum (peak) plasma concentration (C max) and the area under the plasma
      concentration-time curve (AUC) were estimated. RESULTS: Among the 32 subjects, 27
      completed the study. No serious adverse events were observed. The mean
      concentration-time profiles of the test formulation tended to be higher than
      those of the reference formulation. The mean C max values of the two products
      were similar (142 mIU/mL for reference vs. 143 mIU/mL for test), but the mean AUC
      from time zero to infinity (AUCinfinity) values of the test drug were
      approximately 25 % higher than those of the reference drug (9403 mIU.h/mL for
      reference vs. 11,817 mIU.h/mL for test). The GMR (90 % CI) of the test
      formulation to the reference formulation for C max, AUC from time zero to the
      last measurable time (AUClast), and AUCinfinity were 1.03 (0.93-1.14), 1.25 (1.18
      1.33), and 1.27 (1.19-1.35), respectively. CONCLUSION: A single subcutaneous
      injection of either DA-3803 or Ovidrel((r)) was safe and well-tolerated. A
      comparative pharmacokinetics study showed that DA-3803 was bioequivalent to
      Ovidrel((r)) in the C max value but non-equivalent in the AUC value. These
      pharmacokinetic differences may not be expected to affect therapeutic efficacy of
      these two drugs, but further clinical studies are warranted to confirm their
      therapeutic equivalence.

PMID- 25998211
TI  - Design Rationale and Development Approach for Pegfilgrastim as a Long-Acting
      Granulocyte Colony-Stimulating Factor.
AB  - Filgrastim, a recombinant methionyl human granulocyte colony-stimulating factor
      (G-CSF) (r-metHuG-CSF), is efficacious in stimulating neutrophil production and
      maturation to prevent febrile neutropenia (FN) in response to chemotherapy.
      Because of its relatively short circulating half-life, daily filgrastim
      injections are required to stimulate neutrophil recovery. In an effort to develop
      a long-acting form of filgrastim that was as safe and efficacious as filgrastim
      but had a longer in vivo residence time, a number of strategies were considered.
      Ultimately, fusion of filgrastim to polyethylene glycol (PEG) was selected.
      Following extensive analysis of conjugation chemistries as well as in vitro and
      in vivo characterization of a panel of PEGylated proteins, a construct containing
      a 20 kDa PEG moiety covalently conjugated to the N-terminus of filgrastim was
      chosen for advancement as pegfilgrastim. Pegfilgrastim is primarily cleared by
      neutrophils and neutrophil precursors (rather than the kidneys), meaning that
      clearance from the circulation is self-regulating and pegfilgrastim is eliminated
      only after neutrophils start to recover. Importantly, addition of PEG did not
      alter the mechanism of action and safety profile compared to filgrastim. Clinical
      evaluation revealed that a single 6 mg dose effectively reduces the duration of
      neutropenia and risk of FN in patients receiving chemotherapy. This work
      demonstrates the benefit of using PEGylation to generate pegfilgrastim, which
      allows for once-per-chemotherapy cycle administration while maintaining similar
      safety and efficacy profiles as those for multiple daily administration of
      filgrastim. Approaches that may provide advances for therapeutic agonists of G
      CSF receptor are also discussed.

PMID- 25998213
TI  - Flexible two-dimensional Tin+1Cn (n = 1, 2 and 3) and their functionalized MXenes
      predicted by density functional theories.
AB  - Two-dimensional (2D) transition metal carbides/nitrides Mn+1Xn labeled as MXenes
      are attracting increasing interest due to promising applications as Li-ion
      battery anodes and hybrid electro-chemical capacitors. To realize MXenes devices
      in future flexible practical applications, it is necessary to have a full
      understanding of the mechanical properties of MXenes under deformation. In this
      study, we extensively investigated the stress-strain curves and the deformation
      mechanisms in response to tensile stress by first principles calculations using
      2D Tin+1Cn (n = 1, 2 and/or 3) as examples. Our results show that 2D Ti2C can
      sustain large strains of 9.5%, 18% and 17% under tensions of biaxial and uniaxial
      along x and y, respectively, which respectively increase to 20%, 28% and 26.5%
      for 2D Ti2CO2 due to surface functionalizing oxygen, which is much better than
      graphene (15% biaxial). The failure of 2D Tin+1Cn MXene is due to the significant
      collapse of the surface atomic layer; however, surface functionalization could
      slow down this collapse, resulting in the improvement of mechanical flexibility.
      We have also discussed the critical strains and Young's modulus of 2D Tin+1Cn and
      Tin+1CnO2. Our results provide an insight into the microscopic deformation
      mechanism of MXenes and hence benefit their applications in flexible electronic
      devices. 

PMID- 25998214
TI  - JS-X syndrome: A multiple congenital malformation with vocal cord paralysis, ear
      deformity, hearing loss, shoulder musculature underdevelopment, and X-linked
      recessive inheritance.
AB  - We report on a family with a not earlier described multiple congenital
      malformation. Several male family members suffer from laryngeal obstruction
      caused by bilateral vocal cord paralysis, outer and middle ear deformity with
      conductive and sensorineural hearing loss, facial dysmorphisms, and
      underdeveloped shoulder musculature. The affected female members only have middle
      ear deformity and hearing loss. The pedigree is suggestive of an X-linked
      recessive inheritance pattern. SNP-array revealed a deletion and duplication on
      Xq28 in the affected family members. A possible aetiology is a neurocristopathy
      with most symptoms expressed in structures derived from branchial arches. 

PMID- 25998215
TI  - Letter to the Editor regarding "Protective effect of resveratrol against
      cisplatin-induced ototoxicity in HEI-OC1 auditory cells".

PMID- 25998216
TI  - Objective measurement of high-level auditory cortical function in children.
AB  - OBJECTIVE: This study examined whether the N2 latency of the cortical auditory
      evoked potential (CAEP) could be used as an objective indicator of temporal
      processing ability in normally hearing children. METHODS: The N2 latency was
      evoked using three temporal processing paradigms: (1) differences in voice-onset
      times (VOTs); (2) speech-in-noise using the CV/da/embedded in broadband noise
      (BBN) with varying signal-to-noise ratios (SNRs); and (3) 16Hz amplitude
      modulated (AM) BBN presented (i) alone and (ii) following an unmodulated BBN,
      using four modulation depths. Thirty-four school-aged children with normal
      hearing, speech, language and reading were stratified into two groups: 5-7 years
      (n=13) and 8-12 years (n=21). RESULTS: The N2 latency shifted significantly and
      systematically with differences in VOT and SNR, and was significantly different
      in the two AM-BBN conditions. CONCLUSIONS: For children without an N1 peak in the
      cortical waveform, the N2 peak can be used as a sensitive measure of temporal
      processing for these stimuli. SIGNIFICANCE: N2 latency of the CAEP can be used as
      an objective measure of temporal processing ability in a paediatric population
      with temporal processing disorder who are difficult to assess via behavioural
      response.

PMID- 25998217
TI  - E-cigarettes: Considerations for the otolaryngologist.
AB  - PURPOSE: To review the literature regarding electronic cigarettes and discuss
      potential implications and need for advocacy for the pediatric otolaryngologist.
      BACKGROUND: Electronic cigarettes (e-cigarettes) are battery-operated devices
      that deliver nicotine-containing vapors via inhalation. Research on the health
      related consequences of e-cigarettes is ongoing and safety has yet to be
      established. E-cigarettes are not presently under the regulation of any national
      governing body with wide accessibility to minors. Use of these products has
      substantially increased since arrival to the market, particularly within the
      adolescent population. These products are marketed via various platforms
      including television, Internet and social media. Hundreds of flavors are offered
      and e-cigarettes are packaged in various colors. Not only are the ill health
      effects and addictive quality of nicotine concerning, these products have the
      potential to serve as a gateway for minors to tobacco use. APPLICATIONS: The
      relationship between tobacco use, secondhand smoke exposure and otolaryngology
      specific diseases has well been defined. As use of electronic cigarettes
      increases, pediatric otolaryngologists should be aware of the ongoing literature
      regarding these products and to be prepared to counsel families accordingly.
      CONCLUSIONS: The use of e-cigarettes among teenagers, potential implications of
      secondhand vapor exposure from parents and friends, and concerns this may
      encourage adolescents to utilize conventional tobacco products needs to be
      considered.

PMID- 25998218
TI  - Holidays, celebrations, and commiserations: measuring drinking during feasting
      and fasting to improve national and individual estimates of alcohol consumption.
AB  - BACKGROUND: Accurate measures of alcohol consumption are critical in assessing
      health harms caused by alcohol. In many countries, there are large discrepancies
      between survey-based measures of consumption and those based on alcohol sales. In
      England, surveys measuring typical alcohol consumption account for only around
      60% of alcohol sold. Here, using a national survey, we measure both typical
      drinking and atypical/special occasion drinking (i.e., feasting and fasting) in
      order to develop more complete measures of alcohol consumption. METHODS: A
      national random probability telephone survey was implemented (May 2013 to April
      2014). Inclusion criteria were resident in England and aged 16 years or over.
      Respondents (n = 6,085) provided information on typical drinking (amounts per
      day, drinking frequency) and changes in consumption associated with routine
      atypical days (e.g., Friday nights) and special dinking periods (e.g., holidays)
      and events (e.g., weddings). Generalized linear modelling was used to identify
      additional alcohol consumption associated with atypical/special occasion drinking
      by age, sex, and typical drinking level. RESULTS: Accounting for atypical/special
      occasion drinking added more than 120 million UK units of alcohol/week (~12
      million bottles of wine) to population alcohol consumption in England. The
      greatest impact was seen among 25- to 34-year-olds with the highest typical
      consumption, where atypical/special occasions added approximately 18 units/week
      (144 g) for both sexes. Those reporting the lowest typical consumption (<=1
      unit/week) showed large relative increases in consumption (209.3%) with most
      drinking associated with special occasions. In some demographics, adjusting for
      special occasions resulted in overall reductions in annual consumption (e.g.,
      females, 65 to 74 years in the highest typical drinking category). CONCLUSIONS:
      Typical drinking alone can be a poor proxy for actual alcohol consumption.
      Accounting for atypical/special occasion drinking fills 41.6% of the gap between
      surveyed consumption and national sales in England. These additional units are
      inevitably linked to increases in lifetime risk of alcohol-related disease and
      injury, particularly as special occasions often constitute heavy drinking
      episodes. Better population measures of celebratory, festival, and holiday
      drinking are required in national surveys in order to adequately measure both
      alcohol consumption and the health harms associated with special occasion
      drinking.

PMID- 25998219
TI  - New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding
      gamma-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis
      Syndrome (Berdon Syndrome).
AB  - OBJECTIVE: To identify the molecular basis for prenatally suspected cases of
      megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in
      3 independent families with clinical and radiographic evidence of MMIHS. METHODS:
      Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. RESULTS: We
      identified a novel heterozygous de novo missense variant in ACTG2 c.770G>A
      (p.Arg257His) encoding x03B3;-2 smooth muscle actin (ACTG2) in 2 siblings with
      MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo
      missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2
      additional MMHIS patients. All of our patients had evidence of fetal megacystis
      and a normal or slightly increased amniotic fluid volume. Additional findings
      included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient
      dilated bowel loops. ACTG2 immunostaining of the intestinal tissue showed an
      altered muscularis propria, a markedly thinned longitudinal muscle layer, and a
      reduced amount and abnormal distribution of ACTG2. CONCLUSION: Our study
      demonstrates that de novo mutations in ACTG2 are a cause of fetal megacystis in
      MMIHS and that gonadal mosaicism may be present in a subset of cases. These
      findings have implications for the counseling of families with a diagnosis of
      fetal megacystis with a preserved amniotic fluid volume and associated
      gastrointestinal findings.

PMID- 25998220
TI  - Trends in paediatric macrolide use in five European countries-a population-based
      study.
AB  - PURPOSE: The study aims to analyse overall as well as subgroup-specific
      outpatient paediatric macrolide use in five European countries, including time
      trends of macrolide prescription rates, and to provide potential targets for
      future interventions aiming to promote judicious macrolide use. METHODS:
      Macrolide prescription rates per 1000 person years to paediatric outpatients
      (<=18 years) were calculated using healthcare databases from Denmark, Germany,
      Italy, The Netherlands and the UK. Poisson regression analysis was used to
      estimate the influence of increasing calendar year on total macrolide and
      subgroup-specific prescription rates based on monthly data, adjusted for seasonal
      variations. Time periods for which data were available varied between 4 (Italy
      2007-10, Germany 2005-8) and 10 years (UK 2000-9). RESULTS: Paediatric macrolide
      use in 2008 varied between 199 (Italy) and 47 (Netherlands) prescriptions per
      1000 person years. Prescription rates of short-acting macrolides declined
      significantly in all countries but the UK. The use of intermediate-acting
      macrolides significantly rose with increasing calendar year in Denmark (rate
      ratio (RR) = 1.12) and the UK (RR = 1.06), but decreased in Germany (RR = 0.84)
      and The Netherlands (RR = 0.97). Prescription rates of long-acting agents
      increased in Denmark (RR = 1.05), The Netherlands (RR = 1.05) and the UK (RR =
      1.11) (all trends p < 0.05). The greatest seasonal variations of macrolide use
      between summer and winter months were observed in Italy and Germany. CONCLUSIONS:
      The observed trend toward increased prescribing of intermediate- and/or long
      acting agents might further increase resistance pressure on bacterial pathogens
      due to their prolonged plasma half-life and broader antibacterial activity.
      Marked seasonality of prescription rates in the high-utilising countries, Italy
      and Germany, suggests frequent prescription of macrolides to treat respiratory
      infections which may be of viral origin.

PMID- 25998222
TI  - Effect of Anterior Ankle-Foot Orthoses on Weight Shift in Persons With Stroke.
AB  - OBJECTIVE: To examine the effects of an anterior ankle-foot orthosis (AAFO) on
      the speed and accuracy of weight shift in persons with stroke. DESIGN: Cross
      sectional, repeated measures. SETTING: Neurologic rehabilitation department.
      PARTICIPANTS: People with stroke (N=24) who were unable to voluntarily dorsiflex
      the foot against gravity. INTERVENTION: The weight-shift performance was measured
      with and without the AAFO. MAIN OUTCOME MEASURES: The speed and accuracy of
      sustained and cyclic bilateral weight shift were measured using the computerized
      dynamic posturography. The movement velocity, maximum excursion, and directional
      control of sustained weight shift were calculated using the limits of stability
      test. The on-axis velocity gap, directional control, and stability of cyclic
      bilateral weight shift were calculated using the rhythmic weight shift test.
      RESULTS: For sustained weight shift, the maximum excursion of weight shift to the
      affected side was greater with the AAFO (P=.002). For cyclic bilateral weight
      shift, the on-axis velocity gap in the mediolateral (ML) direction was smaller at
      a fast speed (P=.004). The stability of the ML and anteroposterior weight shift
      was higher at slow (P=.002 and P<.001, respectively) and fast (P=.001 and P<.001,
      respectively) speeds when wearing the AAFO. CONCLUSIONS: The findings
      demonstrated that persons with stroke who wear an AAFO might improve the
      excursion of the sustained weight shift to the affected side and the speed and
      stability of cyclic bilateral weight shift in the ML direction.

PMID- 25998223
TI  - Adjunct prednisone therapy for patients with community-acquired pneumonia.

PMID- 25998221
TI  - Differences in the Community Built Environment Influence Poor Perceived Health
      Among Persons With Spinal Cord Injury.
AB  - OBJECTIVE: To assess the association between characteristics of the built
      environment and differences in perceived health among persons with spinal cord
      injury (SCI) using objective measures of the local community derived from
      Geographic Information Systems data. DESIGN: Secondary analysis of cross
      sectional survey data. SETTING: Community. PARTICIPANTS: Persons with chronic SCI
      enrolled in the Spinal Cord Injury Model Systems database (N=503). All cases were
      residents of New Jersey, completed an interview during the years 2000 through
      2012, had a complete residential address, and were community living at the time
      of follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Perceived
      health. RESULTS: Bivariate tests indicated that persons with SCI residing in
      communities with more (vs less) mixed land use and small (vs large) amounts of
      open space were more likely to report poor perceived health. No associations were
      found between perceived health and differences in the residential or destination
      density of the community. Adjusting for variation in demographic, impairment,
      quality of life, and community socioeconomic characteristics accounted for the
      gap in the odds of reporting poor health between persons living in areas with
      large versus small amounts of open space (odds ratio [OR], 0.54; 95% confidence
      interval [CI], 0.28-1.02). However, even after accounting for individual
      background differences, persons living in communities characterized by more
      heterogeneous land use were twice as likely to report poor health compared with
      persons living in less mixed areas (OR, 2.14; 95% CI, 1.12-4.08). CONCLUSIONS:
      Differences in the built characteristics of communities may be important to the
      long-term health and well-being of persons with SCI who may have greater exposure
      to the features of their local area because of limited mobility. The results of
      this study suggest living in a community with more heterogeneous land use was not
      beneficial to the perceived health of persons with chronic SCI living in New
      Jersey. Further investigation is needed to assess if the relationships observed
      in this analysis are influenced by differences in infrastructure and resources
      across communities. Further research is also needed to investigate the role built
      environment plays in the long-term health and well-being of persons with SCI in
      other geographic locales.

PMID- 25998224
TI  - Knockdown of ILK inhibits glioma development via upregulation of E-cadherin and
      downregulation of cyclin D1.
AB  - Integrin-linked kinase (ILK) is a highly conserved serine-threonine protein
      kinase that interacts with cytoplasmic domains of integrin subunits in tumor
      tissues. However, the relationship between gliomas and ILK is elusive. The
      present study aimed to investigate the role of ILK in a human glioma cell line
      (U251). ILK stable expressing vector, U251ILK-PGFP-V-RS-shRNA, was established
      and named as U251-si. The empty-PGFP-V-RS-shRNA (U251-N) was employed as the
      control. Quantitative real-time PCR and western blot analysis were used to detect
      ILK and E-cadherin mRNA and protein expression, respectively. Cell cycle analysis
      was employed to examine the cell cycle distribution. Cell migration was detected
      using a wound healing assay, and cell invasion was detected using a Transwell
      invasion assay. Tumor size and weight were also examined. The results indicated
      that ILK was expressed at a lower level at both the mRNA and protein levels in
      the U251-si group compared with the U251-N group (p<0.01). ILK knockdown
      suppressed cell proliferation of the glioma cells. Knockdown of ILK reduced the
      migratory and invasive potentials of the glioma cells. Inhibition of ILK
      expression upregulated E-cadherin and downregulated cyclin D1 in the glioma cells
      compared to the U251-N group (p<0.05). Knockdown of ILK in the U251 cells
      attenuated the ability of U251 cells to form tumors in nude mice and impaired
      glioma cell in vivo tumorigenicity. In conclusion, knockdown of ILK inhibits
      glioma cell migration, invasion and proliferation through upregulation of E
      cadherin and downregulation of cyclin D1. Our results suggest that ILK may serve
      as a promising therapeutic target for glioma.

PMID- 25998225
TI  - Reference Intervals of Serum Procalcitonin Are Affected by Postnatal Age in Very
      Low Birth Weight Infants during the First 60 Days after Birth.
AB  - BACKGROUND: Procalcitonin (PCT) may be a more sensitive marker for neonatal
      bacterial infections than C-reactive protein (CRP). However, the reference
      intervals of serum PCT were not sufficiently studied in neonates older than 1
      week of age, especially for very low birth weight infants. OBJECTIVES: This study
      investigated the reference level of serum PCT for neonates according to
      gestational age (GA) and postnatal age (PNA). METHODS: Serum PCT was measured in
      914 blood samples from 7-60 days after birth in 415 neonates including 184
      premature infants. Infants with sepsis, congenital anomaly, or clinically evident
      intra-amniotic infections were excluded. Multivariate analysis of covariance was
      used to detect the interaction between GA and PNA. To compare subgroups
      dichotomized by GA and PNA, analysis of covariance was performed with clinical
      parameters as covariates to obtain an adjusted p value. RESULTS: Serum PCT levels
      were negatively correlated with GA, PNA, birth weight, birth height, and platelet
      count, and positively correlated with white blood cell count, absolute neutrophil
      count, hematocrit, and serum CRP after logarithmic transformation. Reference
      intervals of serum PCT were established according to GA and PNA. High PCT levels
      were found in infants with GA <=32 weeks and PNA 7-30 days. CONCLUSION: The
      reference levels of serum PCT were determined according to GA and PNA. As the
      reference PCT levels of infants with GA <=32 weeks were affected by PNA, cautious
      interpretation of PCT levels in these infants is warranted.

PMID- 25998226
TI  - Histological and immunohistological analysis of degenerative changes in the
      cranial cruciate ligament in a canine model of excessive tibial plateau angle.
AB  - OBJECTIVE: To create a canine model of excessive tibial plateau angle (eTPA) and
      assess the chondroid metaplasia and extracellular matrix alteration in the
      cranial cruciate ligament. METHODS: Seven mature female Beagles were included.
      Cylindrical osteotomy was performed bilaterally in the proximal tibia. The TPA
      was increased to approximately 40 degrees  in the left tibia (eTPA stifle) and
      left unchanged in the right tibia (control stifle). Exercise stress was started
      at three months postoperatively, and at 12 months postoperatively the dogs were
      euthanatized and the cranial cruciate ligaments were collected. The specimens
      were subjected to haematoxylin and eosin staining to assess the ligamentocyte
      morphology and immunostaining to assess the type I (COLI), type II (COLII), and
      type III (COLIII) collagen, and the sry-type HMG box 9 (SOX9) staining. RESULTS:
      Macroscopic cranial cruciate ligament injury was absent in six dogs but present
      in the eTPA stifle of one dog, which was excluded from the analysis. The
      ligamentocyte density decreased and the percentage of round ligamentocytes
      increased in the eTPA stifles. The COLII, COLIII, and SOX9 staining increased
      significantly and COLI deposition decreased in the eTPA stifles compared to the
      control stifle. CLINICAL SIGNIFICANCE: The extracellular matrix changed, COLI
      deposition decreased, and COLIII and SOX9 staining increased in the cranial
      cruciate ligament of the eTPA stifles. SOX9 may contribute to COLII synthesis in
      the extracellular matrix of the cranial cruciate ligament in eTPA stifles, and
      eTPA may promote chondroid metaplasia and extracellular matrix alteration.

PMID- 25998227
TI  - Targeting the neurokinin-1 receptor inhibits growth of human colon cancer cells.
AB  - The substance P (SP)/neurokinin-1 receptor (NK1R) complex and the Wnt cascade are
      pivotal signaling pathways in the regulation of cell growth and hence, potent
      targets for future anticancer therapies. However, while the Wnt cascade has long
      been associated with colon cancer, little is known about the expression of the
      NK1R complex as a potential target in this tumor and its molecular basis in
      tumorigenesis in general. We treated the human colon cancer cell lines LiM6 and
      DLD1 with the NK1R antagonist and the clinical drug aprepitant (AP) and analyzed
      both growth response and downstream mechanisms using MTT-assay, reverse phase
      protein array (RPPA), western blot, Super TOP/FOP, confocal microscopy, and
      sphere formation ability (SFA) assays. Following NK1R blockage, we found
      significant growth inhibition of both colon cancer cell lines. When analyzing
      downstream mechanisms, we found a striking inhibition of the canonical Wnt
      pathway represented by decreased Super TOP/FOP and increased membrane
      stabilization of beta-catenin. This effect was independent from baseline Wnt
      activity and mutational status of beta-catenin. Further, treatment of colon
      cancer cells grown under cancer stem cell (CSC) conditions reduced sphere
      formation in both number and size after a single treatment period. We show that
      the NK1R can be a potent anticancer target in colon cancer and that NK1R
      antagonists could potentially serve as future anticancer drugs. This effect was
      seen not only in primary cancer cells but, for the first time, also in CSC-like
      cells, potentially including these cells in a therapeutic effect. Also, we
      describe the robust inhibition of canonical Wnt signaling through targeting the
      SP/NK1R signaling cascade. These findings give important insight into the
      molecular mechanisms of the SP/NK1R complex as a critical component in
      tumorigenesis and could help to identify future anticancer therapies for colon
      and other Wnt-activated cancers.

PMID- 25998229
TI  - Usage and users of online self-management programs for adult patients with atopic
      dermatitis and food allergy: an explorative study.
AB  - BACKGROUND: Two online self-management programs for patients with atopic
      dermatitis (AD) or food allergy (FA) were developed with the aim of helping
      patients cope with their condition, follow the prescribed treatment regimen, and
      deal with the consequences of their illness in daily life. Both programs consist
      of several modules containing information, personal stories by fellow patients,
      videos, and exercises with feedback. Health care professionals can refer their
      patients to the programs. However, the use of the program in daily practice is
      unknown. OBJECTIVE: The aim of this study was to explore the use and
      characteristics of users of the online self-management programs "Living with
      eczema," and "Living with food allergy," and to investigate factors related to
      the use of the trainings. METHODS: A cross-sectional design was carried out in
      which the outcome parameters were the number of log-ins by patients, the number
      of hits on the system's core features, disease severity, quality of life, and
      domains of self-management. Descriptive statistics were used to summarize sample
      characteristics and to describe number of log-ins and hits per module and per
      functionality. Correlation and regression analyses were used to explore the
      relation between the number of log-ins and patient characteristics. RESULTS:
      Since the start, 299 adult patients have been referred to the online AD program;
      173 logged in for at least one occasion. Data from 75 AD patients were available
      for analyses. Mean number of log-ins was 3.1 (range 1-11). Linear regression with
      the number of log-ins as dependent variable showed that age and quality of life
      contributed most to the model, with betas of .35 ( P=.002) and .26 (P=.05),
      respectively, and an R(2) of .23. Two hundred fourteen adult FA patients were
      referred to the online FA training, 124 logged in for at least one occasion and
      data from 45 patients were available for analysis. Mean number of log-ins was 3.0
      (range 1-11). Linear regression with the number of log-ins as dependent variable
      revealed that adding the self-management domain "social integration and support"
      to the model led to an R(2) of .13. The modules with information about the
      disease, diagnosis, and treatment were most visited. Most hits were on the
      information parts of the modules (55-58%), followed by exercises (30-32%).
      CONCLUSIONS: The online self-management programs "Living with eczema" and "Living
      with food allergy" were used by patients in addition to the usual face-to-face
      care. Almost 60% of all referred patients logged in, with an average of three log
      ins. All modules seemed to be relevant, but there is room for improvement in the
      use of the training. Age, quality of life, and lower social integration and
      support were related to the use of the training, but only part of the variance in
      use could be explained by these variables.

PMID- 25998228
TI  - Gene expression studies of a human monocyte cell line identify dissimilarities
      between differently manufactured glatiramoids.
AB  - Glatiramer Acetate (GA) has provided safe and effective treatment for multiple
      sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise
      mechanism of action remains to be fully elucidated, and no validated
      pharmacokinetic or pharmacodynamic biomarkers exist. In order to better
      characterize GA's biological impact, genome-wide expression studies were
      conducted with a human monocyte (THP-1) cell line. Consistent with previous
      literature, branded GA upregulated anti-inflammatory markers (e.g. IL10), and
      modulated multiple immune-related pathways. Despite some similarities,
      significant differences were observed between expression profiles induced by
      branded GA and Probioglat, a differently-manufactured glatiramoid purported to be
      a generic GA. Key results were verified using qRT-PCR. Genes (e.g. CCL5, adj. p <
      4.1 * 10(-5)) critically involved in pro-inflammatory pathways (e.g. response to
      lipopolysaccharide, adj. p = 8.7 * 10(-4)) were significantly induced by
      Probioglat compared with branded GA. Key genes were also tested and confirmed at
      the protein level, and in primary human monocytes. These observations suggest
      differential biological impact by the two glatiramoids and warrant further
      investigation.

PMID- 25998230
TI  - Use of juvenile animal studies to support oncology medicine development in
      children.
AB  - Childhood cancer has remained a challenge because of long-term effects in
      children. The need to extend access of children into new cancer therapies
      requires early prediction of specific safety aspects and juvenile animal studies
      (JAS) are being conducted to screen for age-related toxicities and differences
      occurring during postnatal development. This paper investigates oncology approved
      medicines in the EU (1995-2014) and PIP (Paediatric Investigation Plans - 2007
      2014), regarding the usefulness of JAS in their non-clinical development by
      evaluating information on the medicines labelling. The retrospective review from
      medicines and PIPs revealed a steady use of JAS to better characterize safety:
      Approximately 1 in 3 oncology medicine or PIP has conducted JAS. For 6 of the
      cancer medicines with JAS the toxicity profile in adult and juvenile animals
      showed some differences in study findings. The discussion of these cases is
      illustrative of the potential significance that JAS have provided in oncology
      medicines. 

PMID- 25998231
TI  - Pharmacokinetic Profile of Eight Phenolic Compounds and Their Conjugated
      Metabolites after Oral Administration of Rhus verniciflua Extracts in Rats.
AB  - Rhus verniciflua (Toxicodendron vernicifluum) is a medicinal tree popularly used
      in Asian countries such as China, Japan, and Korea as a food additive or herbal
      medicine because of its beneficial effects. R. verniciflua extract (RVE) contains
      diverse phenolic compounds, such as flavonoids, as its major biological active
      constituents. In this study, the pharmacokinetic profiles of eight phenolic
      compounds were investigated following oral administration of RVE to rats. The
      eight phenolic compounds were 2,4-dihydroxybenzoic acid, 3,4-dihydroxybenzoic
      acid, fisetin, fustin, butin, sulfuretin, taxifolin, and garbanzol. The plasma
      concentrations of the eight compounds were determined by using a liquid
      chromatography-triple-quadrupole mass spectrometer before and after treatment
      with beta-glucuronidase. When 1.5 g/kg RVE was administered, the eight compounds
      were all detected in plasma, mainly as conjugated forms. These pharmacokinetic
      data would be useful for understanding the pharmacological effects of RVE. 

PMID- 25998233
TI  - Longitudinal Evaluation of the Structural Integrity of Teeth Affected by Molar
      Incisor Hypomineralisation.
AB  - The aim of this prospective cohort study was to evaluate the risk of posteruptive
      breakdown and the development of caries lesions in teeth with molar incisor
      hypomineralisation (MIH). A total of 367 permanent incisors and first molars,
      affected and not affected by MIH lesions, of 45 children with MIH from
      Araraquara, Sao Paulo, Brazil, were evaluated at intervals from 6 to 12 months by
      assessing the severity of MIH, the presence of tooth caries lesions and the
      treatment needed. During the study period, all patients received preventive care.
      The data were analysed using Fisher's exact test and actuarial method survival
      analysis. Significant associations were also found in teeth between the presence
      of MIH and a DMFT index >0 in all periods and also between the need for treatment
      and the presence of MIH. The teeth affected by MIH opacities were healthy in 99%
      of incisors and 93% of molars at the end of the 12-month period. Due to the high
      likelihood of maintaining the tooth structure in opacities, the complete or
      premature removal of the affected area is not justified.

PMID- 25998232
TI  - Fucoidan inhibits the migration and proliferation of HT-29 human colon cancer
      cells via the phosphoinositide-3 kinase/Akt/mechanistic target of rapamycin
      pathways.
AB  - Fucoidan, a sulfated polysaccharide, has a variety of biological activities,
      including anti-cancer, anti-angiogenic and anti-inflammatory effects. However,
      the underlying mechanisms of fucoidan as an anti-cancer agent remain to be
      elucidated. The present study examined the anti-cancer effect of fucoidan on HT
      29 human colon cancer cells. The cell growth of HT29 cells was significantly
      decreased following treatment with fucoidan (200 ug/ml). In addition, fucoidan
      inhibited the migration of HT-29 cells by decreasing the expression levels of
      matrix metalloproteinase-2 in a dose-dependent manner (0-200 ug/ml). The
      underlying mechanism of these inhibitory effects included the downregulation of
      phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) by
      treatment with fucoidan. Furthermore, fucoidan increased the expression of
      cleaved caspase-3 and decreased cancer sphere formation. The present study
      suggested that fucoidan exerts an anti-cancer effect on HT-29 human colon cancer
      cells by downregulating the PI3K-Akt-mTOR signaling pathway. Therefore, fucoidan
      may be a potential therapeutic reagent against the growth of human colon cancer
      cells.

PMID- 25998234
TI  - Intracytoplasmic sperm injection outcomes with cryopreserved testicular sperm
      aspiration samples.
AB  - Intracytoplasmic sperm injection (ICSI) may be performed with testicular frozen
      thawed spermatozoa in patients with nonobstructive azoospermia (NOA). Sperm
      retrieval can be performed in advance of oocyte aspiration, as it may avoid the
      possibility of no recovery of spermatozoa on the day of oocyte pickup. There are
      few studies available in the literature concerning the use of frozen-thawed
      spermatozoa obtained from testicular sperm aspiration (TESA). To evaluate the
      effects and the outcomes of ICSI with frozen-thawed spermatozoa obtained by TESA,
      we performed a retrospective analysis of 43 ICSI cycles using frozen-thawed TESA.
      We obtained acceptable results with a fertilisation rate of 67.9%, an
      implantation rate (IR) of 17.1%, and clinical and ongoing pregnancy rates of
      41.9% and 37.2% respectively. The results of this study suggest that performing
      ICSI using cryopreserved frozen-thawed testicular spermatozoa with TESA as a
      first option is a viable, safe, economic and effective method for patients with
      NOA. 

PMID- 25998236
TI  - How well do preschoolers identify healthy foods? Development and preliminary
      validation of the Dietary Interview Assessing Nutritional Awareness (DIANA).
AB  - The current study aimed to develop and initially validate a brief Dietary
      Interview Assessing Nutritional Awareness (DIANA) that mapped onto the Stop-Light
      Diet System. Participants for this study included 69 preschool children (83%
      boys; mean age = 5.13 years; 86% Latino) recruited from two summer programs.
      Children were presented with 24 pictures and were asked to name the food and
      indicate how healthy they felt each food was by pointing to a smiley face (very
      healthy = Green/Go food), neutral face (somewhat healthy = Yellow/Slow food), or
      a sad face (not healthy at all = Red/Whoa foods). Psychometric properties of the
      DIANA were assessed via a baseline assessment while children were re-administered
      the DIANA within 4-6 weeks to ascertain the test-retest reliability. Discriminant
      validity was also assessed in an exploratory fashion with a small subsample (n =
      11) of children who participated in a healthy-lifestyle intervention program
      (HIP). Results indicated that the internal consistency of the DIANA for both the
      expressive knowledge and the health classification scales was acceptable (alpha =
      .83 and .82, respectively) along with the test-retest reliability (ICC = .86 and
      .81, respectively). Lastly, children who participated in HIP experienced greater
      gains in their ability to classify food based on the Stop-Light System and
      greater expressive knowledge of Green/Go foods compared to children who did not
      participate in the intervention suggesting adequate construct validity. These
      findings highlight the feasibility and utility of the DIANA in assessing young
      children's knowledge of foods and their relative healthiness as well as its
      potential sensitivity to intervention effects.

PMID- 25998237
TI  - Clinical differences in children with autism spectrum disorder with and without
      food selectivity.
AB  - Several studies have described the atypical eating behaviors frequently occurring
      in children with Autism Spectrum Disorder (ASD), and food selectivity is the most
      frequent of these problems. The everyday management of mealtime behaviors among
      children with ASD can have a negative impact on family routines and become a
      significant stressor for families. However, much remains unknown about why food
      selectivity is so prevalent among individuals with ASD. The objective of this
      study was to investigate clinical and behavioral features in individuals with ASD
      with the aim of identifying distinctive clinical profiles in children with and
      without food selectivity. A total of 158 children with ASD were enrolled in this
      study: 79 participants with food selectivity (FS) were age and sex matched with
      79 participants without food selectivity (No FS). All participants and their
      parents completed a battery of psychological tests for a comprehensive evaluation
      of ASD symptoms, cognitive abilities, adaptive skills, behavioral problems and
      parental stress level. No statistically significant difference on
      gastrointestinal symptoms and growth adequacy was found between the FS group and
      the No FS group. Overall, the FS group showed significantly higher rates of ASD
      symptoms as compared to the No FS group in the questionnaires completed by
      parents. Furthermore, parents of the FS group reported significantly higher
      levels of parental stress and a larger degree of their children's behavioral
      problems as compared to the No FS group. Finally, there were no differences
      between the FS and the No FS group on any adaptive skill domain. Our findings
      suggest that the identification of distinctive clinical and behavioral patterns
      in children with ASD and food selectivity is a crucial issue for parents and
      therapists in the daily management. 

PMID- 25998238
TI  - Historical Aspects of Lithopaidion.

PMID- 25998239
TI  - Congenital middle ear anomalies: anatomical and functional results of surgery.
AB  - The aim of this study was to describe the audiometric results following surgery
      in a consecutive series of pediatric patients with a congenital middle ear
      disorder. Retrospective chart review was performed for 29 consecutive children
      who underwent 33 middle ear surgeries for congenital ossicular chain anomaly
      between 1990 and 2012. Anomalies were classified into four groups according to
      the Teunissen and Cremers classification. Audiological parameters using four
      frequency averages (0.5, 1, 2 and 4 kHz) were assessed pre- and postoperatively.
      Clinical and audiometric follow-up times were, respectively, 49 +/- 8 and 35 +/-
      5 months (mean +/- SEM). Fifty-eight percent of all patients achieved an air-bone
      gap (ABG) <=20 dB, 62.5% in class I, 50% in class II and 57.9% in class III. The
      improvement of the mean ABG was 13.6 dB, 19.2 dB for class I, 0.2 dB in class II
      and 15.4 dB in class III. Overall mean pure-tone averages improved 14.8 dB with
      13.9 dB for class I; there was no improvement for class II and 20.2 dB for class
      III. The sensorineural hearing loss rate was 9%. This pediatric series showed
      that hearing results depend on type of anomaly. Class I and class III showed
      better hearing improvement than class II.

PMID- 25998240
TI  - Cardiac Tamponade on the Edge.

PMID- 25998235
TI  - Implications of learning theory for developing programs to decrease overeating.
AB  - Childhood obesity is associated with medical and psychological comorbidities, and
      interventions targeting overeating could be pragmatic and have a significant
      impact on weight. Calorically dense foods are easily available, variable, and
      tasty which allows for effective opportunities to learn to associate behaviors
      and cues in the environment with food through fundamental conditioning processes,
      resulting in measurable psychological and physiological food cue reactivity in
      vulnerable children. Basic research suggests that initial learning is difficult
      to erase, and that it is vulnerable to a number of phenomena that will allow the
      original learning to re-emerge after it is suppressed or replaced. These
      processes may help explain why it may be difficult to change food cue reactivity
      and overeating over the long term. Extinction theory may be used to develop
      effective cue-exposure treatments to decrease food cue reactivity through
      inhibitory learning, although these processes are complex and require an integral
      understanding of the theory and individual differences. Additionally, learning
      theory can be used to develop other interventions that may prove to be useful.
      Through an integration of learning theory, basic and translational research, it
      may be possible to develop interventions that can decrease the urges to overeat,
      and improve the weight status of children. 

PMID- 25998241
TI  - Experimental demonstration of a non-resonant hyperlens in the visible spectral
      range.
AB  - A metamaterial hyperlens offers a solution to overcome the diffraction limit by
      transforming evanescent waves responsible for imaging subwavelength features of
      an object into propagating waves. However, the first realizations of optical
      hyperlenses were limited by significant resonance-induced losses. Here we report
      the experimental demonstration of a non-resonant waveguide-coupled hyperlens
      operating in the visible wavelength range. A detailed investigation of various
      materials systems proves that a radial fan-shaped configuration is superior to
      the concentric layer-based configuration in that it relies on non-resonant
      negative dielectric response, and, as a result, enables low-loss performance in
      the visible range. 

PMID- 25998242
TI  - Histopathology of the idiopathic interstitial pneumonias (IIP): A review.
AB  - The 2013 American Thoracic Society/European Respiratory Society consensus
      classification update of the idiopathic interstitial pneumonias (IIP) included
      several important modifications to the organization and spectrum of the diseases
      that were proposed in an earlier multidisciplinary consensus document in 2002.
      The histopathology of the now 'major' and 'rare' IIP is presented here with
      exposition of the newly included entity of a distinctive upper lobe fibrotic lung
      disease referred to as idiopathic pleuroparenchymal fibroelastosis. The 'rare
      histological patterns' of acute fibrinous and organizing pneumonia and
      bronchiolocentric patterns of interstitial pneumonia are illustrated and
      discussed. 

PMID- 25998243
TI  - Preliminary pages.

PMID- 25998244
TI  - 'Innovations in Reproductive Immunobiology', ASRI 35th Annual Meeting, June 2 -
      5, 2015, Queen's University, Kingston, Ontario, Canada.

PMID- 25998245
TI  - Aim for the Suprasternal Notch: Technical Note to Avoid Bowstringing after Deep
      Brain Stimulation.
AB  - BACKGROUND: Bowstringing may occur when excessive fibrosis develops around
      extension cables in the neck after deep brain stimulation (DBS) surgery. Though
      the occurrence of this phenomenon is rare, we have noted that it tends to cause
      maximal discomfort when the cables cross superficially over the convexity of the
      clavicle. We hypothesise that bowstringing may be avoided by directing the
      extension cables towards the suprasternal notch. METHODS: When connecting DBS
      leads to an infraclavicular pectoral implantable pulse generator (IPG),
      tunnelling is directed towards the suprasternal notch, before being directed
      laterally towards the IPG pocket. In previously operated patients with
      established fibrosis, the fibrous tunnel is opened and excised as far cranially
      as possible, allowing medial rerouting of cables. Using this approach, we
      reviewed our series of patients who underwent DBS surgery over 10 years. RESULTS:
      In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the
      clavicle complaining of bowstringing underwent cable exploration and rerouting.
      This eliminated bowstringing and provided better cosmetic results. When the cable
      trajectory was initially directed towards the suprasternal notch, no bowstringing
      was observed. CONCLUSION: The tunnelling trajectory appears to influence
      postoperative incidence of fibrosis associated with DBS cables. Modifying the
      surgical technique may reduce the incidence of this troublesome adverse event.

PMID- 25998246
TI  - Functional role of oppA encoding an oligopeptide-binding protein from
      Lactobacillus salivarius Ren in bile tolerance.
AB  - Lactobacillus salivarius is a member of the indigenous microbiota of the human
      gastrointestinal tract (GIT), and some L. salivarius strains are considered as
      probiotics. Bile tolerance is a crucial property for probiotic bacteria to
      survive the transit through the GIT and exert their beneficial effects. In this
      work, the functional role of oppA encoding an oligopeptide transporter substrate
      binding protein from L. salivarius Ren in bile salt tolerance was investigated.
      In silico analysis revealed that the oppA gene encodes a 61.7-kDa cell surface
      anchored hydrophilic protein with a canonical lipoprotein signal peptide.
      Homologous overexpression of OppA was shown to confer 20-fold higher tolerance to
      0.5 % oxgall in L. salivarius Ren. Furthermore, the recombinant strain exhibited
      1.8-fold and 3.6-fold higher survival when exposed to the sublethal concentration
      of sodium taurocholate and sodium taurodeoxycholate, respectively, while no
      significant change was observed when exposed to sodium glycocholate and sodium
      glycodeoxycholate (GDCA). Our results indicate that OppA confers specific
      resistance to taurine-conjugated bile salts in L. salivarius Ren. In addition,
      the OppA overexpression strain also showed significant increased resistance to
      heat and salt stresses, suggesting the protective role of OppA against multiple
      stresses in L. salivarius Ren. 

PMID- 25998247
TI  - Lysophosphatidylcholine promotes SREBP-2 activation via rapid cholesterol efflux
      and SREBP-2-independent cytokine release in human endothelial cells.
AB  - Lysophosphatidylcholine (LPC) and oxysterols which are major components in
      oxidized low-density lipoprotein have been shown to possess an opposite effect on
      the expression of sterol regulatory element-binding protein-2 (SREBP-2) target
      genes in endothelial cells. In this study, we aimed at elucidating the mechanisms
      of activation of SREBP-2 by LPC and evaluating the effects of LPC and 25
      hydroxycholesterol (25-HC) on the release of inflammatory cytokines. Human
      umbilical vein endothelial cells were treated with LPC or oxysterols including 25
      HC. LPC activated SREBP-2 within 15 min, resulting in induction of expression of
      SREBP-2 target genes which were involved in intracellular cholesterol
      homeostasis. The rapid activation of SREBP-2 was caused by enhanced efflux of
      intracellular cholesterol, which was evaluated using (14)C-acetate. The LPC
      induced activation of SREBP-2 was inhibited by addition of 25-HC. In contrast,
      both LPC and 25-HC increased release of interleukin-6 (IL-6) and IL-8,
      respectively and additively. In conclusion, LPC activated SREBP-2 via enhancement
      of cholesterol efflux, which was suppressed by 25-HC. The release of inflammatory
      cytokines such as IL-6 and IL-8 in endothelial cells was SREBP-2-independent. LPC
      and 25-HC may act competitively in cholesterol homeostasis but additively in
      inflammatory cytokine release. 

PMID- 25998248
TI  - Functional analysis of conserved motifs in a bacterial tyrosine kinase, BtkB,
      from Myxococcus xanthus.
AB  - Myxococcus xanthus has two bacterial protein-tyrosine (BY) kinases, BtkA and
      BtkB. Autophosphorylation in C-terminal tyrosine-rich clusters and poly(Glu, Tyr)
      kinase activities of cytoplasmic catalytic domains of BtkA and BtkB were
      activated by the intracellular juxtamembrane regions of the second transmembrane
      helices. Protein kinase activity against poly(Glu, Tyr) of cytoplasmic fragment
      of BtkB (CF-BtkB) containing an activator region was not inhibited by
      serine/threonine protein kinase inhibitors. However, addition of tyrosine protein
      kinase inhibitors, genistein and 4-amino-5-(4-chlorophenyl)-7-(t
      butyl)pyrazolo[3,4-d]pyrimidine (PP2), at a concentration of 0.2 mM, inhibited
      the CF-BtkB kinase activity by 20 and 64%, respectively. A CF-BtkB mutant
      constructed by replacing all C-terminal tyrosine residues with phenylalanines,
      did not undergo autophosphorylation. Further, this mutation did not significantly
      affect poly(Glu, Tyr) kinase activity, suggesting that M. xanthus BtkB kinase
      activity is not dependent on autophosphorylation in the C-terminal tyrosine
      cluster. A conserved motif (ExxRxxR) of BY kinases is involved in the self
      association of catalytic domains of BY kinases, necessary to accomplish trans
      phosphorylation. An ExxRxxR motif mutant of CF-BtkB led to loss of
      autophosphorylation and poly(Glu, Tyr) kinase activities. These observations
      provide insights into the regulation mechanism of M. xanthus BY kinase activity. 

PMID- 25998249
TI  - Characterization, validation and application of a DNA microarray for the
      detection of mandatory and other waterborne pathogens.
AB  - Culture methods for the detection of indicator bacteria are currently used for
      detection of waterborne bacteria. The need for an increased range of analyzed
      bacteria coupled with the obtainment of rapid and early results justify the
      development of a DNA microarray for the identification of waterborne pathogens.
      This DNA microarray has 16 implanted probes with a median size of 147 bases,
      targeting 12 different parameters, including all mandatory indicator
      microorganisms, such as Escherichia coli, Clostridium perfringens, Pseudomonas
      aeruginosa, Staphylococcus aureus, total and fecal coliforms and enterococci. The
      validation performed with DNA extracted from pure microbial cultures showed the
      suitability of the probes for detection of the target microorganism. To overcome
      the high dilution of water samples it was included either a prior culture step of
      bacterial contaminants retained after filtering 100 ml of water, or a 10-fold
      increase in the volume of filtered water, that resulted in the increase of the
      detected bacteria. The analysis of complex environmental water samples using
      culture methods and the DNA microarray revealed that the latter detected the same
      parameters plus other bacteria tested only in the DNA microarray. The results
      show that this DNA microarray may be a useful tool for water microbiological
      surveillance. 

PMID- 25998251
TI  - Note of concern.

PMID- 25998250
TI  - Property of lysosomal storage disease associated with midbrain pathology in the
      central nervous system of Lamp-2-deficient mice.
AB  - Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon
      disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy,
      and variable mental retardation. To elucidate the function of LAMP-2 in the
      central nervous system, we investigated the neuropathological changes in Lamp-2
      deficient mice. Immunohistochemical observations revealed that Lamp-1 and
      cathepsin D-positive lysosomal structures increased in the large neurons of the
      mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive
      materials were detected in these neurons. By means of ultrastructural studies, we
      found various-shaped accumulations, including lipofuscin, glycolipid-like
      materials, and membranous structures, in the neurons and glial cells of Lamp-2
      deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte
      lysosomes but were not observed in neurons. These pathological features indicate
      lysosomal storage disease; however, the findings are unlikely a consequence of
      deficiency of a single lysosomal enzyme. Although previous study results have
      shown a large amount of autophagic vacuoles in parenchymal cells of the visceral
      organs, these findings were rarely detected in the brain tissue except for some
      axons in the substantia nigra, in which abundant activated microglial cells with
      increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous
      system has a possible role in the degradation of the various macromolecules in
      lysosomes and an additional function concerning protection from oxidative stress,
      especially in the substantia nigra.

PMID- 25998252
TI  - Hydroxyurea-mediated release of nitric oxide in myeloproliferative neoplasms
      patients: Effects on platelet-leukocyte interaction.

PMID- 25998253
TI  - Inactivation of Escherichia Coli O157:H7 and Salmonella Enterica on Blueberries
      in Water Using Ultraviolet Light.
AB  - Ultraviolet light (UV) has antimicrobial effects, but the shadowing effect has
      limited its application. In this study, a novel setup using UV processing in
      agitated water was developed to inactivate Escherichia coli O157:H7 and
      Salmonella on blueberries. Blueberries were dip- or spot-inoculated with E. coli
      or Salmonella. Blueberries inoculated with E. coli were treated for 2 to 10 min
      with UV directly (dry UV) or immersed in agitated water during UV treatment (wet
      UV). E. coli was most easily killed on spot-inoculated blueberries with a 5.2-log
      reduction after 10-min wet UV treatment. Dip-inoculated blueberries were the most
      difficult to be decontaminated with only 1.6-log reduction after 10-min wet UV
      treatment. Wet UV treatment generally showed higher efficacies than dry UV
      treatment, achieving an average of 1.4 log more reduction for spot-inoculated
      blueberries. For dip-inoculated blueberries, chlorine washing and UV treatments
      were less effective, achieving <2 log reductions of E. coli. Thus, the efficacy
      of combinations of wet UV with sodium dodecyl sulfate (SDS), levulinic acid, or
      chlorine was evaluated. Inoculated blueberries were UV-treated while being
      immersed in agitated water containing 100 ppm SDS, 0.5% levulinic acid or 10 ppm
      chlorine. The 3 chemicals did not significantly enhance the wet UV treatment.
      Findings of this study suggest that UV treatment could be used as an alternative
      to chlorine washing for blueberries and potentially for other fresh produce.
      PRACTICAL APPLICATION: A novel UV light system for decontamination of blueberries
      in water was developed and evaluated. Results demonstrated that the
      decontamination efficacy of this system was generally as effective as chlorine
      washing, indicating that it could potentially be used as an alternative to
      chlorine washing for blueberries and other fresh produce.

PMID- 25998254
TI  - Thermodynamic Protein Destabilization by GFP Tagging: A Case of Interdomain
      Allostery.
AB  - The Engrailed Homeodomain (EnHD) transcription factor of Drosophila melanogaster
      was fused to the enhanced green fluorescent protein (eGFP) either at its C- or N
      terminus via three- or ten-residue flexible linkers. Here, we show that EnHD
      undergoes destabilization upon fusing it to eGFP regardless of the linker length
      used and whether the tethering is to its N- or C-terminus. The destabilization is
      reflected in melting points that are lower by up to 9 degrees C. Thermodynamic
      analysis and coarse-grained molecular dynamic simulations indicate that this
      destabilization is due to eGFP-promoted entropic stabilization of the denatured
      state ensemble of EnHD. Our results provide, therefore, an example for
      destabilizing interdomain allostery. They are also important given the widespread
      use of eGFP tagging in cell biology, as they indicate that such tagging can cause
      unintended protein destabilization and concomitant effects. 

PMID- 25998255
TI  - A novel method of reduction for first-time acute lateral patellar dislocations in
      children and adolescents.
AB  - Five pediatric patients with acute traumatic "first-time" lateral patellar
      dislocations were successfully reduced using a novel, atraumatic, and simple
      technique. Uniquely, unlike the traditional method of patellar reduction, the
      patellar dislocations were reduced without any direct manipulation of the
      patella. In co-operative patients, no analgesia was required. Further validation
      of the reproducibility of the effectiveness of this method for successful
      patellar reduction in pediatric and adult populations are required. 

PMID- 25998256
TI  - Pre-Sleep and Sleeping Platform Construction Behavior in Captive Orangutans
      (Pongo spp.): Implications for Ape Health and Welfare.
AB  - The nightly construction of a 'nest' or sleeping platform is a behavior that has
      been observed in every wild great ape population studied, yet in captivity, few
      analyses have been performed on sleep related behavior. Here, we report on such
      behavior in three female and two male captive orangutans (Pongo spp.), in a
      natural light setting, at the Indianapolis Zoo. Behavioral samples were
      generated, using infrared cameras for a total of 47 nights (136.25 h), in summer
      (n = 25) and winter (n = 22) periods. To characterize sleep behaviors, we used
      all-occurrence sampling to generate platform construction episodes (n = 217).
      Orangutans used a total of 2.4 (SD = 1.2) techniques and 7.5 (SD = 6.3) actions
      to construct a sleeping platform; they spent 10.1 min (SD - 9.9 min) making the
      platform and showed a 77% preference for ground (vs. elevated) sleep sites.
      Comparisons between summer and winter platform construction showed winter start
      times (17:12 h) to be significantly earlier and longer in duration than summer
      start times (17:56 h). Orangutans should be provisioned with seasonally
      appropriate, high quality materials suitable for construction of sleeping
      platforms to increase sleep quality and improve animal health and welfare.

PMID- 25998257
TI  - Spontaneous rupture of the pregnant uterus following salpingectomy: a literature
      review.
AB  - BACKGROUND: Spontaneous rupture of the uterus is a life-threatening obstetric
      complication in rare cases associated with previously performed salpingectomy.
      AIM: This paper presents an analysis of uterine rupture cases during pregnancy in
      patients after surgical removal of the fallopian tubes. METHODS: The English and
      Polish language literature was reviewed for studies published between January 1,
      1980 and September 30, 2014 to identify articles that described rupture of the
      uterus in women with a previous history of salpingectomy. RESULTS: Thirteen case
      reports and case series studies in 18 women were identified. 33% of cases of
      uterine rupture following salpingectomy occurred during intrauterine pregnancy,
      whereas the rest was associated with interstitial ectopic pregnancy. Laparoscopic
      salpingectomy more often resulted in rupture of the uterus during non-ectopic
      pregnancy as compared to laparotomy (4 vs. 2 cases, respectively). When
      interstitial pregnancies were excluded, uterine rupture was a cause of fetal
      death in 67% of reported gestations. There were no cases of maternal mortality.
      Conservative treatment was the preferred management option, and total
      hysterectomy was performed in only 2 patients. CONCLUSION: Particular attention
      should be paid to patients with a previous history of salpingectomy due to the
      risk of uterine rupture throughout the entire pregnancy.

PMID- 25998258
TI  - Prevalence and factors associated with sex trading in the year prior to entering
      treatment for drug misuse in England.
AB  - BACKGROUND: This study estimates the past year prevalence of and factors
      associated with sex trading (offering sex for money, drugs or something else)
      among 1796 men and women presenting to 342 drug misuse treatment agencies in
      England, and identifies service development and delivery implications. METHODS:
      Secondary analysis of baseline data from a prospective cohort was conducted.
      Short Form-12 measured mental and physical wellbeing, psychiatric diagnoses were
      self-reported and the circumstances, motivation and readiness tool assessed
      readiness for/pressure to enter treatment. Logistic regression models determined
      associations with sex trading separately by sex. Inverse probability population
      weights were calculated, utilising demographics from the National Drug Treatment
      Monitoring System and agency specific data collection windows. RESULTS: The
      estimated prevalence rate of sex trading in the past 12 months was 5.1% (15.0%
      for women and 2.1% for men). For women, adjusted models identified crack use (aOR
      1.83, 95% CI 1.22-2.74, p=0.004), previous treatment (aOR 3.00, 95% CI 1.31-6.86,
      p=0.010) and greater readiness for treatment (aOR 1.12, 95% CI 1.01-1.24,
      p=0.027) as independently associated with sex trading. For men, lower mental
      wellbeing (aOR 0.97, 95% CI 0.94-0.99, p=0.030) was independently associated and
      marginal effects were identified for syringe sharing (aOR 2.89, 95% CI 0.94-8.86,
      p=0.064) and unprotected sex (aOR 2.23, 95% CI 0.95-5.26, p=0.065). CONCLUSIONS:
      Sex trading among drug misusers is associated with additional health risks and
      specific treatment needs. Given the scale of the problem it is important that
      treatment providers have the competencies to adequately address the issue and
      provide accessible and appropriate services.

PMID- 25998260
TI  - Instant power generation from an air-breathing paper and pencil based bacterial
      bio-fuel cell.
AB  - We present a low-cost, disposable microbial fuel cell fabricated on a paper based
      platform, having a start-up time of 10 s. The platform deploys ordinary pencil
      strokes for graphite electrode deposition. The device uses a membrane-less design
      in a one-time injection (OTI) mode or a continuous capillary driven flow mode
      (CPF), where oxygen from the atmosphere is used up at the cathode for water
      formation, leading to the generation of bioelectricity. The performance of the
      fuel cell is evaluated using two bacterial strains, namely, Pseudomonas
      aeruginosa IIT BT SS1 and Shewanella putrefaciens. This flexible device is shown
      to retain bacteria for a period of at least one hour, resulting in the generation
      of almost 0.4 V using P. aeruginosa and a maximum current of 18 MUA using S.
      putrefaciens without the use of any additional catalysts. 

PMID- 25998261
TI  - Cognitive rehabilitation in multiple sclerosis: A systematic review.
AB  - BACKGROUND: Cognitive impairment is a common clinical feature of multiple
      sclerosis (MS) at both the earlier and later stages of the disease, and has a
      significant impact on patients' functional status and quality of life. The need
      to address this deficit should be taken into account in clinical practice and
      research studies. OBJECTIVE: To conduct an updated systematic review of all
      published studies of cognitive rehabilitation interventions in people with MS,
      including studies with methodological shortcomings, to highlight major strengths
      and weaknesses in the field and to provide directions for future research. SEARCH
      METHODS: We searched electronic databases (PubMed and Web of Science) for
      articles published in English up until January 2014. The reference lists of all
      identified articles were also searched to complete the initial list of
      references. DATA EXTRACTION: Articles were categorized into outcome measures:
      cognition, imaging, mood, fatigue, quality of life and self-perceived cognitive
      deficits. All articles were reviewed independently and assessed according to
      predetermined criteria. RESULTS: A total of 33 studies met the inclusion criteria
      of which 4 were of Level II-1 and none was Level I. Although the majority of
      these studies reported some improvements in cognitive abilities (N=31), the
      evidence which has been reported in the literature remains inconclusive and no
      definite conclusions can be drawn about the effect of different types of
      interventions on cognitive rehabilitation outcomes (recommendation C).
      CONCLUSIONS: This review identified conflicting findings in the published
      literature about the effectiveness of various forms of cognitive rehabilitation
      techniques used in patients with MS. Studies with more rigorous methodology are
      therefore needed to clarify which form of cognitive rehabilitation may lead to
      greater clinical improvement.

PMID- 25998259
TI  - Influence of erythropoietin on microvesicles derived from mesenchymal stem cells
      protecting renal function of chronic kidney disease.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) play a central role in the
      remediation of cell and tissue damage. Erythropoietin (EPO) may enhance the
      beneficial influence of MSCs during recovery from tissue and organ injuries.
      Microvesicles (MVs) released from MSCs contribute to the restoration of kidney
      damage. We studied the influence of EPO on MVs derived from MSCs, and the
      protective effects of these factors in subjects with chronic kidney disease
      (CKD). METHODS: The MVs derived from untreated MSCs (MSC-MVs) or from MSCs
      incubated in different concentrations of EPO (1, 10, 100, and 500 IU/ml EPO-MVs)
      were used to treat renal injury of unilateral ureteral obstruction (UUO) in vivo,
      and transforming growth factor-beta1 (TGF-beta1)-induced fibrosis in a human
      renal proximal tubular epithelial (HK2) cell line in vitro. Western blot and
      reverse transcription polymerase chain reaction (RT-PCR) analyses were used to
      evaluate the expression of epithelial and mesenchymal markers in the renal tissue
      and HK2 cells. Flow cytometry was used to assess apoptosis within the HK2 cells,
      and microRNA (miRNA) microarray assays were used to determine the expression
      profiles of miRNA in the MSC-MVs and EPO-MVs. RESULTS: Compared to MSC-MVs
      (untreated), there was a significant increase in the number of EPO-MVs derived
      from MSCs treated with 1-100 IU/ml EPO, and these EPO-MVs had a greater benefit
      in UUO mice on days 7 and 14. Moreover, the EPO-MVs had a better restorative
      effect following TGF-beta1-induced fibrosis in HK2 cells at 24 h and 48 h. The
      flow cytometry results revealed that both types of MVs, especially EPO-MVs, play
      an important anti-apoptotic role in HK2 cells treated with TGF-beta1. The miRNA
      profiles of the MVs revealed that EPO-MVs changed 212 miRNAs (fold-change >=
      1.5), including miR-299, miR-499, miR-302, and miRNA-200, and that 70.28 % of
      these changes involved upregulation. The changed miRNA in EPO-MVs may have
      contributed to their enhanced protective effects following renal injury compared
      to MSC-MVs. CONCLUSIONS: There was a dose-dependent increase in the level of EPO
      MVs within the range of 1-100 IU/ml EPO. Although both MSC-MVs and EPO-MVs
      protect the kidney from fibrosis-related damage, there is a superior effect of
      EPO-MVs.

PMID- 25998262
TI  - The lysis cassette of DLP12 defective prophage is regulated by RpoE.
AB  - Expression of the lysis cassette (essD, ybcT, rzpD/rzoD) from the defective
      lambdoid prophage at the 12th minute of Escherichia coli's genome (DLP12) is
      required in some strains for proper curli expression and biofilm formation.
      Regulating production of the lytic enzymes encoded by these genes is critical for
      maintaining cell wall integrity. In lambdoid phages, late-gene regulation is
      mediated by the vegetative sigma factor RpoD and the lambda antiterminator
      Qlambda. We previously demonstrated that DLP12 contains a Q-like protein (QDLP12)
      that positively regulates transcription of the lysis cassette, but the sigma
      factor responsible for this transcription initiation remained to be elucidated.
      In silico analysis of essDp revealed the presence of a putative - 35 and - 10
      sigma site recognized by the extracytoplasmic stress response sigma factor, RpoE.
      In this work, we report that RpoE overexpression promoted transcription from
      essDp in vivo, and in vitro using purified RNAP. We demonstrate that the - 35
      region is important for RpoE binding in vitro and that this region is also
      important for QDLP12-mediated transcription of essDp in vivo. A bacterial two
      hybrid assay indicated that QDLP12 and RpoE physically interact in vivo,
      consistent with what is seen for Qlambda and RpoD. We propose that RpoE regulates
      transcription of the DLP12 lysis genes through interaction with QDLP12 and that
      proper expression is dependent on an intact - 35 sigma region in essDp. This work
      provides evidence that the unique Q-dependent regulatory mechanism of lambdoid
      phages has been co-opted by E. coli harbouring defective DLP12 and has been
      integrated into the tightly controlled RpoE regulon. 

PMID- 25998264
TI  - Genome of Methanoregula boonei 6A8 reveals adaptations to oligotrophic peatland
      environments.
AB  - Analysis of the genome sequence of Methanoregula boonei strain 6A8, an
      acidophilic methanogen isolated from an ombrotrophic (rain-fed) peat bog, has
      revealed unique features that likely allow it to survive in acidic, nutrient-poor
      conditions. First, M. boonei is predicted to generate ATP using protons that are
      abundant in peat, rather than sodium ions that are scarce, and the sequence of a
      membrane-bound methyltransferase, believed to pump Na+ in all methanogens, shows
      differences in key amino acid residues. Further, perhaps reflecting the
      hypokalemic status of many peat bogs, M. boonei demonstrates redundancy in the
      predicted potassium uptake genes trk, kdp and kup, some of which may have been
      horizontally transferred to methanogens from bacteria, possibly Geobacter spp.
      Overall, the putative functions of the potassium uptake, ATPase and
      methyltransferase genes may, at least in part, explain the cosmopolitan success
      of group E1/E2 and related methanogenic archaea in acidic peat bogs. 

PMID- 25998263
TI  - Phosphoproteomic analysis of the Chlamydia caviae elementary body and reticulate
      body forms.
AB  - Chlamydia are Gram-negative, obligate intracellular bacteria responsible for
      significant diseases in humans and economically important domestic animals. These
      pathogens undergo a unique biphasic developmental cycle transitioning between the
      environmentally stable elementary body (EB) and the replicative intracellular
      reticulate body (RB), a conversion that appears to require extensive regulation
      of protein synthesis and function. However, Chlamydia possess a limited number of
      canonical mechanisms of transcriptional regulation. Ser/Thr/Tyr phosphorylation
      of proteins in bacteria has been increasingly recognized as an important
      mechanism of post-translational control of protein function. We utilized 2D gel
      electrophoresis coupled with phosphoprotein staining and MALDI-TOF/TOF analysis
      to map the phosphoproteome of the EB and RB forms of Chlamydia caviae. Forty-two
      non-redundant phosphorylated proteins were identified (some proteins were present
      in multiple locations within the gels). Thirty-four phosphorylated proteins were
      identified in EBs, including proteins found in central metabolism and protein
      synthesis, Chlamydia-specific hypothetical proteins and virulence-related
      proteins. Eleven phosphorylated proteins were identified in RBs, mostly involved
      in protein synthesis and folding and a single virulence-related protein. Only
      three phosphoproteins were found in both EB and RB phosphoproteomes.
      Collectively, 41 of 42 C. caviae phosphoproteins were present across Chlamydia
      species, consistent with the existence of a conserved chlamydial phosphoproteome.
      The abundance of stage-specific phosphoproteins suggests that protein
      phosphorylation may play a role in regulating the function of developmental-stage
      specific proteins and/or may function in concert with other factors in directing
      EB-RB transitions. 

PMID- 25998265
TI  - Living with constant suffering: a different life following the diagnosis of HIV.
AB  - We used grounded theory in semi-structured interviews with 32 persons living with
      HIV (PLWH) in Barcelona, Spain, and found that PLWH live with constant suffering,
      a core category combining four realities: I need help; My life is constantly
      controlled; I have a new imposed life; and I have an uncertain reality.
      Participants described being constantly controlled by health policies and
      medications. They thought their lives were in the hands of others and that a new
      life, characterized by the constant fear of stigma, had been imposed on them.
      They felt they were losing freedom and vitality, as many questions remained
      unanswered, causing uncertainty related to health and public life. Emotional help
      was obtained mainly from peers and social networks. Our emergent theory shows a
      disruptive experience, with serious consequences to individual and social
      development. Health care has to focus on the real needs of PLWH to reduce
      suffering and uncertainty. 

PMID- 25998266
TI  - Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.
AB  - CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in
      ovarian carcinoma, which is significantly associated with poor prognosis.
      Although the Sp1 protein regulates the expression level of CD147, it remains
      unclear whether Sp1 phosphorylation plays a role in this regulation. A dual
      luciferase assay revealed that T453 and T739 mutations decreased the activity of
      Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and
      protein expression. Western blot analysis showed that CD147 promoted Sp1
      phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In
      addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion
      ability of HO-8910pm cells. Immunohistochemical staining showed that the
      components of the feedback loop were overexpressed in ovarian cancer tissues. The
      correlation analysis revealed a significant correlation between phospho-Sp1
      (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation
      coefficients of r=0.477 and r=0.461, respectively. Collectively, our results
      suggest that a Sp1-CD147 positive feedback loop plays a critical role in the
      invasion ability of ovarian cancer cells.

PMID- 25998267
TI  - Clinical, biochemical and microbiological factors associated with the prognosis
      of pneumococcal meningitis in children.
AB  - BACKGROUND: Pneumococcal meningitis (PM) has a high morbidity and mortality. The
      aim of the study was to evaluate what factors are related to a poor PM prognosis.
      METHODS: Prospective observational study conducted on patients admitted to the
      Pediatric Intensive Care Unit in a tertiary hospital with a diagnosis of PM
      (January 2000 to December 2013). Clinical, biochemical and microbiological data
      were recorded. Variable outcome was classified into good or poor (neurological
      handicap or death). A multivariate logistic regression was performed based on the
      univariate analysis of significant data. RESULTS: A total of 88 patients were
      included. Clinical variables statistically significant for a poor outcome were
      younger age (p=.008), lengthy fever (p=.016), sepsis (p=.010), lower Glasgow
      Score (p<.001), higher score on Pediatric Risk Mortality Score (p=0.010) and
      Sequential Organ Failure Assessment (SOFA) (p<.001), longer mechanical
      ventilation (p=.004), and inotropic support (p=.008) requirements. Statistically
      significant biochemical variables were higher level of C-reactive protein
      (p<.001) and procalcitonin (p=.014) at admission, low cerebrospinal (CSF)
      pleocytosis (p=.003), higher level of protein in CSF (p=.031), and severe
      hypoglycorrhachia (p=.002). In multivariate analysis, independent indicators of
      poor outcome were age less than 2 years (p=.011), high score on SOFA (p=.030),
      low Glasgow Score (p=.042), and severe hypoglycorrhachia (p=.009). CONCLUSIONS:
      Patients younger than 2 years of age, with depressed consciousness at admission,
      especially when longer mechanical ventilation is required, are at high risk of a
      poor outcome.

PMID- 25998268
TI  - Autovalidation rates in an outpatient coagulation laboratory.
AB  - INTRODUCTION: To determine the rates of autovalidation in our outpatient
      coagulation laboratory. METHODS: We retrospectively identified all coagulation
      tests analyzed during the month of January 2014 from our laboratory information
      system (LIS) (N = 16 116), from around 800 000 active members of Clalit Health
      Services (a health maintenance organization). The integrated system includes a
      single centrifugation of all collection tubes, analyzers that rerun or reflex
      tests according to the test results, and a laboratory information system that
      sends orders to the analyzer, autovalidates test results, and automatically sends
      critical value results to a list for immediate physician communication. Reasons
      for technician validation are tests rerun for confirmation or because of analyzer
      errors and test results that require reflex testing. All other test results are
      sent automatically to the laboratory information system without the need for
      technician review. RESULTS: There were 362 test results with analyzer errors, 91
      results rerun for confirmation (thrombophilia test results outside the reference
      interval), and 50 tests with mixing studies and reflex testing for factor XI
      activity levels (total = 3.1%, 503/16116), resulting in an autovalidation rate of
      96.9% (95% confidence interval - 96.6-97.2%). CONCLUSIONS: We conclude that an
      integrated system can result in a high autovalidation rate in a high-volume
      outpatient coagulation laboratory.

PMID- 25998269
TI  - Morphometry of boar sperm head and flagellum in semen backflow after
      insemination.
AB  - Once deposited in the female reproductive system, sperm begin their competition
      and undergo a selection to reach the site of fertilization. Little is known about
      the special characteristics of sperm that reach the oviduct and are able to
      fertilize, with even less information on the role of sperm dimension and shape in
      transport and fertilization. Here, we examine whether sperm morphometry could be
      involved in their journey within the uterus. For this purpose, sperm head
      dimension (length, width, area, and perimeter) and shape (shape factor,
      ellipticity, elongation, and regularity), and flagellum length were analyzed in
      the backflow at different times after insemination (0-15, 16-30, and 31-60
      minutes). Sperm morphometry in the backflow was also analyzed taking into account
      the site of semen deposition (cervical vs. intrauterine). Finally, flagellum
      length was measured at the uterotubal junction. Sperm analyzed in the backflow
      were small (head and flagellum) with different head shapes compared with sperm
      observed in the dose before insemination. The site of deposition influenced head
      morphometry and tail size both being smaller in the backflow after cervical
      insemination compared with intrauterine insemination. Mean tail length of sperm
      collected in the backflow was smaller than that in the insemination dose and at
      the uterotubal junction. Overall, our results suggest that sperm size may be
      involved in sperm transport either because of environment or through sperm
      selection and competence on their way to encounter the female gamete. 

PMID- 25998270
TI  - Effects of two combinations of cryoprotectants on the in vitro developmental
      capacity of vitrified immature porcine oocytes.
AB  - This study evaluated two cryoprotectant (CPA) combinations, ethylene glycol (EG)
      + DMSO and EG + propylene glycol (PG), used for the vitrification of germinal
      vesicle (GV) porcine oocytes. In experiment 1, the equilibration of GV with the
      two CPA combinations increased (P < 0.05) the percentage of oocytes that
      degenerated after IVM (18.1 +/- 2.3% and 19.4 +/- 2.6% for EG + DMSO and EG + PG
      groups, respectively) compared with control oocytes (7.6 +/- 1.3%). However, CPAs
      did not affect the fertilization or developmental parameters of the embryos. In
      experiment 2, the percentages of live vitrified-warmed GV oocytes at 2 hours
      after warming (EG + DMSO: 67.0 +/- 2.3% and EG + PG: 57.6 +/- 2.3%) were lower
      than those of fresh control GV oocytes (97.3 +/- 0.7%). The percentage of
      degenerated oocytes after IVM was higher (P < 0.001) in vitrified-warmed oocytes
      (EG + DMSO: 59.8 +/- 2.3% and EG + PG: 56.2 +/- 2.6%) than in the control (1.6 +/
      1.3). Fertilization efficiency was higher (P < 0.05) in the EG + PG (39.6 +/-
      2.4%) and control (42.0 +/- 2.2%) groups than in the EG + DMSO (26.3 +/- 7.7%)
      group. The cleavage and blastocyst formation rates of the EG + DMSO (25.9 +/-
      3.5% and 6.6 +/- 2.5%, respectively) and EG + PG (20.2 +/- 5.4% and 4.7 +/- 1.6%,
      respectively) vitrification groups were lower (P < 0.001) than those observed in
      the control oocytes (53.4 +/- 2.7% and 31.9 +/- 1.7%, respectively). In
      conclusion, in the absence of vitrification, the toxic effects of both CPA
      combinations on the GV oocytes were minimal. Vitrification resulted in important
      losses in viability at each step of the in vitro embryo production procedure.
      However, the surviving oocytes were able to mature and be fertilized, although
      the fertilization efficiency in the EG + DMSO group was lower. Blastocysts
      formation was similar for both CPA combinations. 

PMID- 25998271
TI  - Transgenic cattle produced by nuclear transfer of fetal fibroblasts carrying Ipr1
      gene at a specific locus.
AB  - This study aimed to assess the effects of the intracellular pathogen resistance 1
      (Ipr1) transgene on preventing infection of Mycobacterium bovis in cattle. A
      specific expression vector for the Ipr1 gene was constructed and inserted in the
      genome between surfactant protein A and methionine adenosyltransferase I of
      bovine fetal fibroblasts. After SCNT, cleavage (86.9% vs. 87.4%, P > 0.05) and
      blastocyst developmental rates (34.6% vs. 33.5%, P > 0.05) were similar between
      transgenic and nontransgenic bovine fetal fibroblasts. Four surviving and one
      dead Ipr1-transgenic female cattle were produced by transfer of the SCNT
      blastocysts. Polymerase chain reaction and Southern blot analyses confirmed that
      the Ipr1 transgene of the cattle was located at the expected site. Inserting Ipr1
      gene did not affect the expression of the surrounding genes. Main death modality
      of M bovis-infected peripheral blood mononuclear cells (PBMCs) derived from Ipr1
      transgenic cattle was apoptosis, whereas that of PBMCs from control cattle was
      necrosis. In addition, the number of colony-forming units in PBMCs of Ipr1
      transgenic cattle was significantly lower than that of the control cattle (P <
      0.05). The finding that expression of Ipr1 transgene in PBMCs significantly
      increased anti-M bovis activity suggested breeding anti-M bovis cattle population
      by the transgenic SCNT technique could be a feasible strategy. 

PMID- 25998272
TI  - Quality improvement of transgenic cloned bovine embryos using an aggregation
      method: Effects on cell number, cell ratio, embryo perimeter, mitochondrial
      distribution, and gene expression profile.
AB  - The production of cloned embryos using conventional methods has extremely low
      success rates owing to low embryo quality. To improve the quality of cloned
      bovine embryos expressing enhanced green fluorescent protein (EGFP), we applied
      an aggregation culture method. The EGFP gene was transfected into bovine fetal
      fibroblasts using a retroviral vector system. Somatic cell nuclear transfer was
      performed using these cells, and the resulting embryos were cultured in
      aggregates or individually. Gene expression was analyzed by a microarray, and
      differentially expressed genes were validated by quantitative real-time
      polymerase chain reaction. The total number of cells per blastocyst and the ratio
      of inner cell mass cells to trophectoderm cells were higher in aggregated
      transgenic cloned blastocysts (agBL; 368.7 +/- 109.6 and 1:4.8, respectively)
      than in in vitro-fertilized blastocysts (ivfBL; 189.8 +/- 65.8 and 1:2.6,
      respectively) and nonaggregated transgenic cloned blastocysts (sBL; 113.1 +/-
      36.3 and 1:1.5, respectively; P < 0.05 and P < 0.01, respectively). Moreover, the
      blastocyst perimeter was larger in the agBL group than in the ivfBL and sBL
      groups (1168.8 +/- 200.23 vs. 887.33 +/- 187.62 and 678 +/- 226.1 MUm; P < 0.05).
      In addition, mitochondrial fluorescence intensity was higher in the agBL group
      than in the ivfBL and sBL groups (P < 0.05). The number of apoptotic cells per
      blastocyst was lower in the ivfBL and agBL groups than in the sBL group (3.7 +/-
      2.2 and 3.4 +/- 2.1 vs. 6.7 +/- 6.8; P < 0.05). The genes identified in the
      microarray belonged to 18 categories. Expression of the Kruppel-like factor 4
      gene, which is associated with cell proliferation, development, and
      transcription, was 7.2-fold higher in the agBL group than in the ivfBL group (P <
      0.05) but did not differ between the sBL and ivfBL groups (P > 0.05). Expression
      of the heat shock 70-kDa protein 1A gene, which is associated with apoptosis, was
      12-fold higher in the sBL group than in the ivfBL and agBL groups (P < 0.05).
      Expression of a stemness-related gene (octamer-binding transcription factor 4)
      and trophectoderm-specific genes (homeobox protein CDX2 and keratin 18) was
      higher in the agBL group than in the sBL group (P < 0.05). However, expression of
      the stemness gene homeobox protein NANOG did not differ among the groups (P >
      0.05). Taken together, these data suggest that the aggregation method improves
      the quality of cloned embryos expressing EGFP and might be helpful in animal
      cloning. 

PMID- 25998273
TI  - Proteomics of endometrial fluid after dexamethasone treatment in mares
      susceptible to endometritis.
AB  - Corticotherapy is a common treatment in mares susceptible to endometritis.
      Isoflupredone improves pregnancy rates and affects the protein profile of
      endometrial fluid in comparison to untreated mares. Dexamethasone decreases
      postbreeding fluid accumulation and uterine edema; however, its effects on the
      protein profile of the endometrial fluid have not yet been studied. The aim of
      the present study was to verify the effect of dexamethasone on the protein
      profile of endometrial fluid, in the presence or absence of infection, from mares
      susceptible to persistent postbreeding endometritis. Nine susceptible mares aged
      between 7 and 18 years were used. After checking for signs of estrus, mares were
      subjected to four treatments: C: mares received no treatment and served as
      control; D: mares received 40-mg dexamethasone at breeding, with collection of
      samples after 6 hours; I-6 and I-24: intrauterine infusion of 1 *
      10(9)Streptococcus zooepidemicus/mL and samples collected after 6 and 24 hours;
      I/D-6 and I/D-24: intrauterine infusion of 1 * 10(9)S zooepidemicus/mL and 40-mg
      dexamethasone, collecting the sample after 6 and 24 hours. All mares were
      subjected to all treatments. Samples were collected and subjected to two
      dimensional electrophoresis and mass spectrometry for the identification of
      relevant protein spots. Corticotherapy altered the protein profile of the
      endometrial fluid of susceptible mares, characterized by an increase and/or
      decrease in the optical density of inflammatory acute-phase proteins. We conclude
      that the use of dexamethasone in mares with and without infection alters the
      protein profile of endometrial fluid of susceptible mares. 

PMID- 25998274
TI  - Augmented short undersized hamstring tendon graft with LARS(r) artificial
      ligament versus four-strand hamstring tendon in anterior cruciate ligament
      reconstruction: preliminary results.
AB  - BACKGROUND: This retrospective study compares the results of reconstruction of
      isolated chronic anterior cruciate ligament rupture using augmented short
      undersized sized hamstring tendon graft with ligament advanced artificial
      reinforcement system (LARS) versus a four-strand hamstring tendon graft (4-SHG).
      Our hypothesis was that postoperative knee stability after using augmented short
      length or small diameter hamstring tendon graft with LARS artificial ligament
      could be significant and satisfactory more than 4-strand hamstring tendon graft
      group. MATERIALS AND METHODS: Between June 2007-July 2008, 72 patients were
      divided into a (LARS) augmented group (n=27) and a (4-SHG) group (n=45). RESULTS:
      Mean FU is 5years. KT-1000 examinations showed that the LARS group had
      significantly less anterior displacement than the (4-SHG) group P=0.013. IKDC
      score demonstrated statistically significant differences (P=0.05). CONCLUSIONS:
      Our study indicates that early results of augmenting: short length or small
      diameter harvested hamstring tendons with LARS in ACL reconstruction provides
      satisfactory, comparable results and displayed higher knee stability compared to
      (4-SHG) group. LEVEL OF EVIDENCE: Level III (case control study).

PMID- 25998275
TI  - Purinergic signaling in retinal degeneration and regeneration.
AB  - Purinergic signaling is centrally involved in mediating the degeneration of the
      injured and diseased retina, the induction of retinal gliosis, and the protection
      of the retinal tissue from degeneration. Dysregulated calcium signaling triggered
      by overactivation of P2X7 receptors is a crucial step in the induction of
      neuronal and microvascular cell death under pathogenic conditions like ischemia
      hypoxia, elevated intraocular pressure, and diabetes, respectively.
      Overactivation of P2X7 plays also a pathogenic role in inherited and age-related
      photoreceptor cell death and in the age-related dysfunction and degeneration of
      the retinal pigment epithelium. Gliosis of micro- and macroglial cells, which is
      induced and/or modulated by purinergic signaling and associated with an impaired
      homeostatic support to neurons, and the ATP-mediated propagation of retinal
      gliosis from a focal injury into the surrounding noninjured tissue are involved
      in inducing secondary cell death in the retina. On the other hand, alterations in
      the glial metabolism of extracellular nucleotides, resulting in a decreased level
      of ATP and an increased level of adenosine, may be neuroprotective in the
      diseased retina. Purinergic signals stimulate the proliferation of retinal glial
      cells which contributes to glial scarring which has protective effects on retinal
      degeneration and adverse effects on retinal regeneration. Pharmacological
      modulation of purinergic receptors, e.g., inhibition of P2X and activation of
      adenosine receptors, may have clinical importance for the prevention of
      photoreceptor, neuronal, and microvascular cell death in diabetic retinopathy,
      retinitis pigmentosa, age-related macular degeneration, and glaucoma,
      respectively, for the clearance of retinal edema, and the inhibition of
      dysregulated cell proliferation in proliferative retinopathies. This article is
      part of a Special Issue entitled 'Purines in Neurodegeneration and
      Neuroregeneration'.

PMID- 25998276
TI  - The influence of allosteric modulators and transmembrane mutations on
      desensitisation and activation of alpha7 nicotinic acetylcholine receptors.
AB  - Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at
      an extracellular orthosteric site. Previous studies have described several
      positive allosteric modulators (PAMs) that are selective for homomeric alpha7
      nAChRs. These include type I PAMs, which exert little or no effect on the rate of
      receptor desensitisation, and type II PAMs, which cause a dramatic loss of
      agonist-induced desensitisation. Here we report evidence that transmembrane
      mutations in alpha7 nAChRs have diverse effects on receptor activation and
      desensitisation by allosteric ligands. It has been reported previously that the
      L247T mutation, located toward the middle of the second transmembrane domain (at
      the 9' position), confers reduced levels of desensitisation. In contrast, the
      M260L mutation, located higher up in the TM2 domain (at the 22' position), does
      not show any difference in desensitisation compared to wild-type receptors. We
      have found that in receptors containing the L247T mutation, both type I PAMs and
      type II PAMs are converted into non-desensitising agonists. In contrast, in
      receptors containing the M260L mutation, this effect is seen only with type II
      PAMs. These findings, indicating that the M260L mutation has a selective effect
      on type II PAMs, have been confirmed both with previously described PAMs and also
      with a series of novel alpha7-selective PAMs. The novel PAMs examined in this
      study have close chemical similarity but diverse pharmacological properties. For
      example, they include compounds displaying effects on receptor desensitisation
      that are typical of classical type I and type II PAMs but, in addition, they
      include compounds with intermediate properties. 

PMID- 25998277
TI  - Tracking individual membrane proteins and their biochemistry: The power of direct
      observation.
AB  - The advent of single molecule fluorescence microscopy has allowed experimental
      molecular biophysics and biochemistry to transcend traditional ensemble
      measurements, where the behavior of individual proteins could not be precisely
      sampled. The recent explosion in popularity of new super-resolution and super
      localization techniques coupled with technical advances in optical designs and
      fast highly sensitive cameras with single photon sensitivity and millisecond time
      resolution have made it possible to track key motions, reactions, and
      interactions of individual proteins with high temporal resolution and spatial
      resolution well beyond the diffraction limit. Within the purview of membrane
      proteins and ligand gated ion channels (LGICs), these outstanding advances in
      single molecule microscopy allow for the direct observation of discrete
      biochemical states and their fluctuation dynamics. Such observations are
      fundamentally important for understanding molecular-level mechanisms governing
      these systems. Examples reviewed here include the effects of allostery on the
      stoichiometry of ligand binding in the presence of fluorescent ligands; the
      observation of subdomain partitioning of membrane proteins due to
      microenvironment effects; and the use of single particle tracking experiments to
      elucidate characteristics of membrane protein diffusion and the direct
      measurement of thermodynamic properties, which govern the free energy landscape
      of protein dimerization. The review of such characteristic topics represents a
      snapshot of efforts to push the boundaries of fluorescence microscopy of membrane
      proteins to the absolute limit. This article is part of the Special Issue
      entitled 'Fluorescent Tools in Neuropharmacology'. 

PMID- 25998278
TI  - Cognitive Enhancement Treatment for People With Mental Illness Who Do Not Respond
      to Supported Employment: A Randomized Controlled Trial.
AB  - OBJECTIVE: Cognitive impairment presents a serious and common obstacle to
      competitive employment for people with severe mental illness, including those who
      receive supported employment. This study evaluated a cognitive enhancement
      program to improve cognition and competitive employment in people with mental
      illness who had not responded to supported employment. METHOD: In a randomized
      controlled trial, 107 people with severe mental illness (46% with schizophrenia
      or schizoaffective disorder) who had not obtained or kept competitive work
      despite receiving high-fidelity supported employment were assigned to receive
      either enhanced supported employment (with specialized cognitive training of
      employment specialists) or enhanced supported employment plus the Thinking Skills
      for Work program, a standardized cognitive enhancement program that includes
      practice of computer cognitive exercises, strategy coaching, and teaching of
      coping and compensatory strategies. Research assistants tracked competitive
      employment weekly for 2 years, and assessors blind to treatment assignment
      evaluated cognitive functioning at baseline, at the end of cognitive enhancement
      training, and 12 and 24 months after baseline. RESULTS: Participants in the
      Thinking Skills for Work group improved more than those in the enhanced supported
      employment only group on measures of cognitive functioning and had consistently
      better competitive employment outcomes during the follow-up period, including in
      jobs obtained (60% compared with 36%), weeks worked (23.9 compared with 9.2), and
      wages earned ($3,421 compared with $1,728). CONCLUSIONS: The findings suggest
      that cognitive enhancement interventions can reduce cognitive impairments that
      are obstacles to work, thereby increasing the number of people who can benefit
      from supported employment and competitive work.

PMID- 25998279
TI  - A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine
      Dependence in Bipolar I Disorder.
AB  - OBJECTIVE: Although drug dependence is common in patients with bipolar disorder,
      minimal data are available on the treatment of drug dependence in this patient
      population. The authors previously reported a decreased risk of relapse to
      cocaine use in a pilot study of citicoline in patients with bipolar disorder and
      cocaine dependence. The primary aim of the present study was to determine whether
      citicoline reduces cocaine use in outpatients with bipolar I disorder and current
      cocaine dependence and active cocaine use. METHOD: A total of 130 outpatients
      with bipolar I disorder (depressed or mixed mood state) and cocaine dependence
      received citicoline or placebo add-on therapy for 12 weeks. Results of thrice
      weekly urine drug screens were analyzed using a generalized linear mixed model
      that was fitted to the binary outcome of cocaine-positive screens at each
      measurement occasion for 12 weeks. Mood was assessed with the Inventory of
      Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and
      the Young Mania Rating Scale. RESULTS: In the intent-to-treat sample (N=61 in
      both groups), significant treatment group and group-by-time effects were
      observed, whether or not missing urine screens were imputed as cocaine positive.
      The group effect was greatest early in the study and tended to decline with time.
      No between-group differences in mood symptoms or side effects were observed.
      CONCLUSIONS: Citicoline was well tolerated for treatment of cocaine dependence in
      patients with bipolar disorder. Cocaine use was significantly reduced with
      citicoline initially, although treatment effects diminished over time, suggesting
      the need for augmentation strategies to optimize long-term benefit.

PMID- 25998280
TI  - Brain Correlates of the Interaction Between 5-HTTLPR and Psychosocial Stress
      Mediating Attention Deficit Hyperactivity Disorder Severity.
AB  - OBJECTIVE: The serotonin transporter 5-HTTLPR genotype has been found to moderate
      the effect of stress on severity of attention deficit hyperactivity disorder
      (ADHD), with stronger effects of stress in carriers of the short allele than in
      individuals homozygous for the long allele. The underlying neurobiological
      mechanism of this gene-environment interaction in ADHD is unknown. The authors
      aimed to determine whether 5-HTTLPR moderates the effect of stress on brain gray
      matter volume and, if so, which brain regions mediate the effect of this gene
      environment interaction on ADHD severity. METHOD: Structural MRI, 5-HTTLPR
      genotype, and stress exposure questionnaire data were available for 701
      adolescents and young adults participating in the multicenter ADHD cohort
      NeuroIMAGE study (from 385 families; 291 with ADHD, 78 with subthreshold ADHD,
      332 healthy comparison subjects; 55.8% male; average age: 17.0 years). ADHD
      symptom count was determined through multi-informant questionnaires. For the
      analysis, a whole-brain voxel-based morphometry approach was combined with
      mediation analysis. RESULTS: Stress exposure was associated with significantly
      less gray matter volume in the precentral gyrus, middle and superior frontal
      gyri, frontal pole, and cingulate gyrus in S-allele carriers compared with
      participants homozygous for the l-allele. The association of this gene
      environment interaction with ADHD symptom count was mediated by gray matter
      volume in the frontal pole and anterior cingulate gyrus. CONCLUSIONS: 5-HTTLPR
      genotype moderates the effect of stress on brain regions involved in social
      cognitive processing and cognitive control. Specifically, regions important for
      cognitive control link this gene-environment interaction to ADHD severity.

PMID- 25998284
TI  - Smoke or fire? Acute pancreatitis and the liraglutide trials.
AB  - Over the past few years, substantial clinical data have been presented showing
      that incretin-based therapies are effective glucose-lowering agents.
      Specifically, glucagon-like peptide 1 receptor agonists demonstrate an efficacy
      comparable to insulin treatment with minimal hypoglycemia and have favorable
      effects on body weight. Thus, many of the unmet clinical needs noted from prior
      therapies are addressed by these agents. However, even after many years of use,
      many continue to raise concerns about the long-term safety of these agents and,
      in particular, the concern with pancreatitis. This clearly remains a complicated
      topic. Thus, in this issue of Diabetes Care, we continue to update our readers on
      this very important issue by presenting two studies evaluating incretin-based
      medications and risk of pancreatitis. Both have undergone significant revisions
      based on peer review that provided significant clarification of the data. We
      applaud both author groups for being extremely responsive in providing the
      additional data and revisions requested by the editorial team. As such, because
      of the critical peer review, we feel both articles achieve the high level we
      require for Diabetes Care and are pleased to now present them to our readers. In
      keeping with our aim to comprehensively evaluate this topic, we asked for
      additional commentaries to be prepared. In the narrative outlined below, Prof.
      Edwin A.M. Gale provides a commentary on the report that focuses on clinical
      trials of liraglutide in the treatment of diabetes. In the narrative that follows
      Prof. Gale's contribution, Dr. Laurent Azoulay provides a commentary about the
      remaining uncertainty in this area and also discusses the results from a
      nationwide population-based case-control study. From the journal's perspective,
      both of the articles on pancreatitis and incretin-based therapies reported in
      this issue have been well vetted, and we feel both of the commentaries are
      insightful.

PMID- 25998285
TI  - Incretin-based drugs and adverse pancreatic events: almost a decade later and
      uncertainty remains.
AB  - Over the past few years, substantial clinical data have been presented showing
      that incretin-based therapies are effective glucose-lowering agents.
      Specifically, glucagon-like peptide 1 receptor agonists demonstrate an efficacy
      comparable to insulin treatment with minimal hypoglycemia and have favorable
      effects on body weight. Thus, many of the unmet clinical needs noted from prior
      therapies are addressed by these agents. However, even after many years of use,
      many continue to raise concerns about the long-term safety of these agents and,
      in particular, the concern with pancreatitis. This clearly remains a complicated
      topic. Thus, in this issue of Diabetes Care, we continue to update our readers on
      this very important issue by presenting two studies evaluating incretin-based
      medications and risk of pancreatitis. Both have undergone significant revisions
      based on peer review that provided significant clarification of the data. We
      applaud both author groups for being extremely responsive in providing the
      additional data and revisions requested by the editorial team. As such, because
      of the critical peer review, we feel both articles achieve the high level we
      require for Diabetes Care and are pleased to now present them to our readers. In
      keeping with our aim to comprehensively evaluate this topic, we asked for
      additional commentaries to be prepared. In the narrative outlined below, Dr.
      Laurent Azoulay provides a commentary about the remaining uncertainty in this
      area and also discusses the results from a nationwide population-based case
      control study. In the narrative preceding Dr. Azoulay's contribution, Prof. Edwin
      A.M. Gale provides a commentary on the report that focuses on clinical trials of
      liraglutide in the treatment of diabetes. From the journal's perspective, both of
      the articles on pancreatitis and incretin-based therapies reported in this issue
      have been well vetted, and we feel both of the commentaries are insightful.

PMID- 25998281
TI  - Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four
      Decade Longitudinal Cohort Study.
AB  - OBJECTIVE: Despite a prevailing assumption that adult ADHD is a childhood-onset
      neurodevelopmental disorder, no prospective longitudinal study has described the
      childhoods of the adult ADHD population. The authors report follow-back analyses
      of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD
      cases diagnosed in childhood, in one cohort. METHOD: Participants belonged to a
      representative birth cohort of 1,037 individuals born in Dunedin, New Zealand, in
      1972 and 1973 and followed to age 38, with 95% retention. Symptoms of ADHD,
      associated clinical features, comorbid disorders, neuropsychological deficits,
      genome-wide association study-derived polygenic risk, and life impairment
      indicators were assessed. Data sources were participants, parents, teachers,
      informants, neuropsychological test results, and administrative records. Adult
      ADHD diagnoses used DSM-5 criteria, apart from onset age and cross-setting
      corroboration, which were study outcome measures. RESULTS: As expected, childhood
      ADHD had a prevalence of 6% (predominantly male) and was associated with
      childhood comorbid disorders, neurocognitive deficits, polygenic risk, and
      residual adult life impairment. Also as expected, adult ADHD had a prevalence of
      3% (gender balanced) and was associated with adult substance dependence, adult
      life impairment, and treatment contact. Unexpectedly, the childhood ADHD and
      adult ADHD groups comprised virtually nonoverlapping sets; 90% of adult ADHD
      cases lacked a history of childhood ADHD. Also unexpectedly, the adult ADHD group
      did not show tested neuropsychological deficits in childhood or adulthood, nor
      did they show polygenic risk for childhood ADHD. CONCLUSIONS: The findings raise
      the possibility that adults presenting with the ADHD symptom picture may not have
      a childhood-onset neurodevelopmental disorder. If this finding is replicated,
      then the disorder's place in the classification system must be reconsidered, and
      research must investigate the etiology of adult ADHD.

PMID- 25998287
TI  - James R. Gavin III, MD, PhD--a humble and remarkable trailblazer, scientist,
      advocate, mentor, and educator for diabetes.

PMID- 25998286
TI  - Progressive renal decline: the new paradigm of diabetic nephropathy in type 1
      diabetes.
AB  - On the basis of extensive studies in Joslin Clinic patients over 25 years, we
      propose a new model of diabetic nephropathy in type 1 diabetes. In this model,
      the predominant clinical feature of both early and late stages of diabetic
      nephropathy is progressive renal decline, not albuminuria. Progressive renal
      decline (estimated glomerular filtration rate loss >3.5 mL/min/year) is a
      unidirectional process that develops while patients have normal renal function.
      It progresses at an almost steady rate until end-stage renal disease is reached,
      albeit at widely differing rates among individuals. Progressive renal decline
      precedes the onset of microalbuminuria, and as it continues, it increases the
      risk of proteinuria. Therefore, study groups ascertained for
      microalbuminuria/proteinuria are enriched for patients with renal decline
      (decliners). We found prevalences of decliners in 10%, 32%, and 50% of patients
      with normoalbuminuria, microalbuminuria, and proteinuria, respectively. Whether
      the initial lesion of progressive renal decline is in the glomerulus, tubule,
      interstitium, or vasculature is unknown. Similarly unclear are the initiating
      mechanism and the driver of progression. No animal model mimics progressive renal
      decline, so etiological studies must be conducted in humans with diabetes.
      Prospective studies searching for biomarkers predictive of the onset and rate of
      progression of renal decline have already yielded positive findings that will
      help to develop not only accurate methods for early diagnosis but also new
      therapeutic approaches. Detecting in advance which patients will have rapid,
      moderate, or minimal rates of progression to end-stage renal disease will be the
      foundation for developing personalized methods of prevention and treatment of
      progressive renal decline in type 1 diabetes.

PMID- 25998288
TI  - Type 1 diabetes at a crossroads!

PMID- 25998289
TI  - Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D
      Exchange clinic registry.
AB  - To examine the overall state of metabolic control and current use of advanced
      diabetes technologies in the U.S., we report recent data collected on individuals
      with type 1 diabetes participating in the T1D Exchange clinic registry. Data from
      16,061 participants updated between 1 September 2013 and 1 December 2014 were
      compared with registry enrollment data collected from 1 September 2010 to 1
      August 2012. Mean hemoglobin A1c (HbA1c) was assessed by year of age from <4 to
      >75 years. The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and
      8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c
      decreased from 8.3% (67 mmol/mol) in 2-4-year-olds to 8.1% (65 mmol/mol) at 7
      years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds.
      Subsequently, mean HbA1c values decline gradually until ~30 years of age,
      plateauing at 7.5-7.8% (58-62 mmol/mol) beyond age 30 until a modest drop in
      HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH)
      and diabetic ketoacidosis (DKA) remain all too common complications of treatment,
      especially in older (SH) and younger patients (DKA). Insulin pump use increased
      slightly from enrollment (58-62%), and use of continuous glucose monitoring (CGM)
      did not change (7%). Although the T1D Exchange registry findings are not
      population based and could be biased, it is clear that there remains considerable
      room for improving outcomes of treatment of type 1 diabetes across all age
      groups. Barriers to more effective use of current treatments need to be addressed
      and new therapies are needed to achieve optimal metabolic control in people with
      type 1 diabetes.

PMID- 25998291
TI  - Predicting type 1 diabetes using biomarkers.
AB  - Clinical type 1 diabetes is preceded by an asymptomatic phase that can be
      identified by serum islet autoantibodies. This perspective proposes that there is
      now sufficient evidence to allow a broader use of islet autoantibodies as
      biomarkers to diagnose type 1 diabetes that is already at an asymptomatic stage,
      so that attempts to prevent clinical hyperglycemia become a feature of disease
      management. Prediction would first, therefore, shift toward the use of genetic
      and other biomarkers to determine the likelihood that islet autoimmunity will
      develop in an infant, and second, toward metabolic assessment to stage and
      biomarkers to determine the rate of progression to hyperglycemia in children in
      whom islet autoimmunity is diagnosed. A case is presented for future
      comprehensive risk assessment that commences at birth and includes attempts to
      predict, stage, and prevent initiation and progression of the disease process at
      multiple stages. The biomarkers required achieving this level of sophistication
      and dissemination are discussed.

PMID- 25998292
TI  - Prevention and reversal of type 1 diabetes--past challenges and future
      opportunities.
AB  - Over the past three decades there have been a number of clinical trials directed
      at interdicting the type 1 diabetes (T1D) disease process in an attempt to
      prevent the development of the disease in those at increased risk or to stabilize
      potentially even reverse-the disease in people with T1D, usually of recent onset.
      Unfortunately, to date there has been no prevention trial that has resulted in
      delay or prevention of T1D. And, trials in people with T1D have had mixed results
      with some showing promise with at least transient improvement in beta-cell
      function compared with randomized control groups, while others have failed to
      slow the decline in beta-cell function when compared with placebo. This
      Perspective will assess the past and present challenges in this effort and
      provide an outline for potential future opportunities.

PMID- 25998290
TI  - Current concepts on the pathogenesis of type 1 diabetes--considerations for
      attempts to prevent and reverse the disease.

PMID- 25998293
TI  - Impact of fat, protein, and glycemic index on postprandial glucose control in
      type 1 diabetes: implications for intensive diabetes management in the continuous
      glucose monitoring era.
AB  - BACKGROUND: Continuous glucose monitoring highlights the complexity of
      postprandial glucose patterns present in type 1 diabetes and points to the
      limitations of current approaches to mealtime insulin dosing based primarily on
      carbohydrate counting. METHODS: A systematic review of all relevant biomedical
      databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register
      of Controlled Trials, was conducted to identify research on the effects of
      dietary fat, protein, and glycemic index (GI) on acute postprandial glucose
      control in type 1 diabetes and prandial insulin dosing strategies for these
      dietary factors. RESULTS: All studies examining the effect of fat (n = 7),
      protein (n = 7), and GI (n = 7) indicated that these dietary factors modify
      postprandial glycemia. Late postprandial hyperglycemia was the predominant effect
      of dietary fat; however, in some studies, glucose concentrations were reduced in
      the first 2-3 h, possibly due to delayed gastric emptying. Ten studies examining
      insulin bolus dose and delivery patterns required for high-fat and/or high
      protein meals were identified. Because of methodological differences and
      limitations in experimental design, study findings were inconsistent regarding
      optimal bolus delivery pattern; however, the studies indicated that high
      fat/protein meals require more insulin than lower-fat/protein meals with
      identical carbohydrate content. CONCLUSIONS: These studies have important
      implications for clinical practice and patient education and point to the need
      for research focused on the development of new insulin dosing algorithms based on
      meal composition rather than on carbohydrate content alone.

PMID- 25998295
TI  - Islet transplantation for type 1 diabetes, 2015: what have we learned from
      alloislet and autoislet successes?
AB  - The therapeutic potential of pancreatic islet allotransplantation, in which human
      donor islets are used, as a treatment for type 1 diabetes (T1D) has fascinated
      diabetes researchers and clinicians for decades. At the same time, the
      therapeutic potential of total pancreatectomy and islet autotransplantation
      (TPIAT) (in which one's own islets are used) as a preventive treatment for
      diabetes in patients who undergo total pancreatectomy for chronic, painful
      pancreatitis has received relatively less attention. This is ironic, since the
      latter has been much more effective than the former in terms of successful
      glucose management and duration of efficacy. The reasons for this disparity can
      be partially identified. TPIAT receives very little attention in textbooks of
      internal medicine and general surgery and surprisingly little print in textbooks
      of endocrinology and transplantation. T1D is much more predominant than TPIAT as
      a clinical entity. Provision of insulin or replacement of islets is mandatory and
      a primary goal in T1D. Provision of pain relief from chronic pancreatitis is the
      primary goal of total pancreatectomy in TPIAT, whereas treatment of diabetes, and
      certainly prevention of diabetes, has been more of a secondary consideration.
      Nonetheless, research developments in both fields have contributed to success in
      one another. In this Perspective, I will provide a brief history of islet
      transplantation and contrast and compare the procedures of allo- and autoislet
      transplantation from three major points of view 1) the procedures of islet
      procurement, isolation, and transplantation; 2) the role and complications of
      immunosuppressive drugs; and 3) the posttransplant consequences on beta- as well
      as alpha-cell function.

PMID- 25998296
TI  - Pathway to artificial pancreas systems revisited: moving downstream.
AB  - Artificial pancreas (AP) systems, a long-sought quest to replicate mechanically
      islet physiology that is lost in diabetes, are reaching the clinic, and the
      potential of automating insulin delivery is about to be realized. Significant
      progress has been made, and the safety and feasibility of AP systems have been
      demonstrated in the clinical research center and more recently in outpatient
      "real-world" environments. An iterative road map to AP system development has
      guided AP research since 2009, but progress in the field indicates that it needs
      updating. While it is now clear that AP systems are technically feasible, it
      remains much less certain that they will be widely adopted by clinicians and
      patients. Ultimately, the true success of AP systems will be defined by
      successful integration into the diabetes health care system and by the ultimate
      metric: improved diabetes outcomes.

PMID- 25998294
TI  - Evidence-informed clinical practice recommendations for treatment of type 1
      diabetes complicated by problematic hypoglycemia.
AB  - Problematic hypoglycemia, defined as two or more episodes per year of severe
      hypoglycemia or as one episode associated with impaired awareness of
      hypoglycemia, extreme glycemic lability, or major fear and maladaptive behavior,
      is a challenge, especially for patients with long-standing type 1 diabetes.
      Individualized therapy for such patients should include a composite target:
      optimal glucose control without problematic hypoglycemia. Therefore, we propose a
      tiered, four-stage algorithm based on evidence of efficacy given the limitations
      of educational, technological, and transplant interventions. All patients with
      problematic hypoglycemia should undergo structured or hypoglycemia-specific
      education programs (stage 1). Glycemic and hypoglycemia treatment targets should
      be individualized and reassessed every 3-6 months. If targets are not met, one
      diabetes technology-continuous subcutaneous insulin infusion or continuous
      glucose monitoring-should be added (stage 2). For patients with continued
      problematic hypoglycemia despite education (stage 1) and one diabetes technology
      (stage 2), sensor-augmented insulin pumps preferably with an automated low
      glucose suspend feature and/or very frequent contact with a specialized
      hypoglycemia service can reduce hypoglycemia (stage 3). For patients whose
      problematic hypoglycemia persists, islet or pancreas transplant should be
      considered (stage 4). This algorithm provides an evidence-informed approach to
      resolving problematic hypoglycemia; it should be used as a guide, with individual
      patient circumstances directing suitability and acceptability to ensure the
      prudent use of technology and scarce transplant resources. Standardized reporting
      of hypoglycemia outcomes and inclusion of patients with problematic hypoglycemia
      in studies of new interventions may help to guide future therapeutic strategies.

PMID- 25998297
TI  - Weight management in type 2 diabetes: current and emerging approaches to
      treatment.
AB  - Diabetes is a growing global health concern, as is obesity. Diabetes and obesity
      are intrinsically linked: obesity increases the risk of diabetes and also
      contributes to disease progression and cardiovascular disease. Although the
      benefits of weight loss in the prevention of diabetes and as a critical component
      of managing the condition are well established, weight reduction remains
      challenging for individuals with type 2 diabetes due to a host of metabolic and
      psychological factors. For many patients, lifestyle intervention is not enough to
      achieve weight loss, and alternative options, such as pharmacotherapy, need to be
      considered. However, many traditional glucose-lowering medications may lead to
      weight gain. This article focuses on the potential of currently available
      pharmacological strategies and on emerging approaches in development to support
      the glycemic and weight-loss goals of individuals with type 2 diabetes. Two
      pharmacotherapy types are considered: those developed primarily for blood glucose
      control that have a favorable effect on body weight and those developed primarily
      to induce weight loss that have a favorable effect on blood glucose control.
      Finally, the potential of combination therapies for the management of obese
      patients with type 2 diabetes is discussed.

PMID- 25998298
TI  - Erratum. Combination of empagliflozin and linagliptin as second-line therapy in
      subjects with type 2 diabetes inadequately controlled on metformin. Diabetes care
      2015;38:384-393.

PMID- 25998299
TI  - Erratum. Initial combination of empagliflozin and linagliptin in subjects with
      type 2 diabetes. Diabetes care 2015;38:394-402.

PMID- 25998301
TI  - Trends and characteristics of self-reported case presentation of diabetes
      diagnosis among youth from 2002 to 2010: findings from the SEARCH for diabetes in
      youth study.

PMID- 25998302
TI  - Role of noninsulin therapies alone or in combination in chromosome 6q24-related
      transient neonatal diabetes: sulfonylurea improves but does not always normalize
      insulin secretion.

PMID- 25998303
TI  - Comment on Udell et al. Saxagliptin and cardiovascular outcomes in patients with
      type 2 diabetes and moderate or severe renal impairment: observations from the
      SAVOR-TIMI 53 Trial. Diabetes Care 2015;38:696-705.

PMID- 25998304
TI  - Comment on Hsu et al. BMI cut points to identify at-risk asian americans for type
      2 diabetes screening. Diabetes Care 2015;38:150-158.

PMID- 25998305
TI  - Comment on Khunti et al. Hypoglycemia and risk of cardiovascular disease and all
      cause mortality in insulin-treated people with type 1 and type 2 diabetes: a
      cohort study. Diabetes care 2015;38:316-322.

PMID- 25998306
TI  - Comment on Hughes et al. An early pregnancy HbA1c >=5.9% (41 mmol/mol) is optimal
      for detecting diabetes and identifies women at increased risk of adverse
      pregnancy outcomes. Diabetes Care 2014;37:2953-2959.

PMID- 25998307
TI  - Response to comment on Hughes et al. An early pregnancy HbA1c >=5.9% (41
      mmol/mol) is optimal for detecting diabetes and identifies women at increased
      risk of adverse pregnancy outcomes. Diabetes Care 2014;37:2953-2959.

PMID- 25998308
TI  - Comment on Genuth. Should sulfonylureas remain an acceptable first-line add-on to
      metformin therapy in patients with type 2 diabetes? No, it's time to move on!
      Diabetes Care 2015;38:170-175.

PMID- 25998309
TI  - Response to comment on Genuth. Should sulfonylureas remain an acceptable first
      line add-on to metformin therapy in patients with type 2 diabetes? No, it's time
      to move on! Diabetes Care 2015;38:170-175.

PMID- 25998310
TI  - International Children's Continence Society standardization report on urodynamic
      studies of the lower urinary tract in children.
AB  - AIMS: The objective of this document created by the ICCS standardization
      subcommittee is to provide a uniform guideline on measurement, quality control
      and documentation of urodynamic studies in children. METHODS: This guideline was
      created using expert opinion and critical review of the published literature on
      urodynamic studies in children. Currently no standardized guideline or level 1
      data exists on the proper technique for this subject matter. RESULTS: The
      document provides a throughout explanation on how to approach a child who
      presents with lower urinary tract dysfunction, whether it be of neurogenic,
      anatomic or functional origin. Formation of an urodynamic question after a
      comprehensive history and physical examination is paramount in selecting the
      urodynamic study(ies) that will be most appropriate for each child. Appropriate
      application of each test with careful consideration of the needs of the child and
      family will provide the most accurate and reproducible results. Recommendations
      on how to execute each of the components of an urodynamic study as well as
      interpretation are included in the document. CONCLUSIONS: Urodynamic studies have
      become a major tool in evaluating lower urinary tract dysfunction in children.
      There are many subtleties in performing these studies in children in
      juxtaposition to adults; therefore, adaptations specific to children must be made
      to achieve accurate and reproducible results. Uniformity in how the studies are
      conducted from center to center will allow for healthier transparency and
      enhanced comparison of results in both clinical and research situations.

PMID- 25998312
TI  - Cadmium Induced Apoptosis in MG63 Cells by Increasing ROS, Activation of p38 MAPK
      and Inhibition of ERK 1/2 Pathways.
AB  - BACKGROUND/AIMS: Cadmium (Cd) induces apoptosis in different kinds of cells,
      including osteoblasts, both in vivo and in vitro. However, little is known about
      the mechanisms by which Cd induces apoptosis. METHODS: In the present study, we
      used the human osteosarcoma cell line MG63, which has characteristics similar to
      human osteoblasts, as an in vitro model to determine the cellular mechanisms by
      which Cd induces apoptosis. RESULTS: We found that short-term exposure to CdCl2
      induced apoptosis in MG63 cells. Furthermore, the incubation of cells with CdCl2
      significantly increased the level of phosphorylated p38MAPK and significantly
      decreased the phosphorylation of ERK1/2 in a concentration-dependent manner.
      Additionally, the inhibition of the phosphorylation of p38 MAPK by SB202190
      protected MG63 cells from Cd-induced apoptosis. The incubation of MG63 cells with
      the ERK1/2 inhibitor PD98059 significantly increased apoptosis in MG63 cells.
      CdCl2 also significantly increased the intracellular levels of ROS. N
      acetylcysteine (NAC) significantly reduced ROS levels and reversed the effects of
      CdCl2 on MAPK signaling. CONCLUSION: Our results suggested that Cd induced
      apoptosis in MG63 cells by increasing ROS, activation of p38 MAPK and inhibition
      of ERK1/2 pathways.

PMID- 25998311
TI  - Community Level Correlates of Low Birthweight Among African American, Hispanic
      and White Women in California.
AB  - OBJECTIVES: Racial and ethnic groups in the US exhibit major differences in low
      birthweight (LBW) rates. While previous studies have shown that community level
      social indicators associated with LBW vary by race and ethnicity, it is not known
      whether these differences exist among racial or ethnic groups who live in the
      same neighborhood or community. To address this question, we examined the
      association of community level features with LBW among African American, White
      and Hispanic women who live in similar geographic areas. METHODS: The analysis is
      based on geocoded birth certificates for all singleton live births in the year
      2000 to women residing in 805 California ZIP codes. Community level social and
      demographic data were obtained from U.S. Census data files for the year 2000 and
      surrogate indices of population level alcohol and drug abuse and dependence were
      derived from hospital discharge data (HDD). Tobit and bootstrap analyses were
      used to test associations with birth outcomes, maternal characteristics, and
      community level social and demographic features within and across the three
      groups of women living in similar geographic areas. RESULTS: The results
      demonstrate major racial and ethnic differences in community level correlates of
      LBW. Rates of LBW among African Americans were lower if they lived in areas that
      were more densely populated, had greater income disparities, were more racially
      segregated, and had low rates of alcohol abuse or dependence. These associations
      were different or absent for Hispanic and White women. CONCLUSIONS FOR PRACTICE:
      The results suggest that despite living in the same areas, major differences in
      neighborhood features and social processes are linked to birth outcomes of
      African American women compared to Hispanic and White women. Further research,
      especially using multilevel approaches, is needed to precisely identify these
      differences to help reduce racial and ethnic disparities in LBW.

PMID- 25998313
TI  - Evaluation of a hypoxia regulated gene panel in ovarian cancer.
AB  - A panel of nine hypoxia regulated genes, selected from a previously published
      fifty gene panel, was investigated for its ability to predict hypoxic ovarian
      cancer phenotypes. All nine genes including vascular endothelial growth factor A,
      glucose transporter 1, phosphoglycerate mutase 1, lactate dehydrogenase A, prolyl
      4-hydroxylase, alpha-polypeptide 1, adrenomedullin, N-myc downstream regulated 1,
      aldolase A, and carbonic anhydrase 9 were upregulated in the HEY and OVCAR-3
      human ovarian cell lines cultured in vitro under hypoxic compared to normoxic
      conditions as measured by quantitative reverse transcription polymerase chain
      reaction (qRT-PCR). The gene panel was also elevated in HEY xenograft tumor
      tissue compared to HEY cells cultured in normoxia. The HEY xenograft tissue
      demonstrated heterogeneous positive immunohistochemical staining for the
      exogenous hypoxia biomarker pimonidazole, and the hypoxia regulated protein
      carbonic anhydrase IX. A quantitative nuclease protection assay (qNPA) was
      developed which included the nine hypoxia regulated genes. The qNPA assay
      provided similar results to those obtained using qRT-PCR for cultured cell lines.
      The qNPA assay was also evaluated using paraffin embedded fixed tissues including
      a set of five patient matched primary and metastatic serous cancers and four
      normal ovaries. In this small sample set the average gene expression was higher
      in primary and metastatic cancer tissue compared to normal ovaries for the
      majority of genes investigated. This study supports further evaluation by qNPA of
      this gene panel as an alternative or complimentary method to existing protein
      biomarkers to identify ovarian cancers with a hypoxic phenotype. 

PMID- 25998314
TI  - Ex Vivo Evaluation of Skin Staples for Typhlotomy Closure in Cattle.
AB  - OBJECTIVE: To compare 2 sutured techniques with a skin stapled technique for
      typhlotomy closure in bovines. STUDY DESIGN: Ex-vivo study. SAMPLE POPULATION:
      Bovine fresh cadaveric ceca (n = 27). METHODS: Typhlotomies (4 cm in length) were
      made on the cecal apex and closed with 1 of the following techniques: hand-sewn,
      2-layer suture consisting of a continuous, full-thickness layer oversewn with a
      Cushing layer (Group FC); hand-sewn, double inverting suture consisting of a 1st
      Cushing layer oversewn with an additional Cushing layer (Group CC); skin staples
      (Group S). Closure time, bursting pressure, and related costs of each technique
      were calculated and compared. RESULTS: Median (range) construction time for group
      S was 1.12 (0.49-1.3) min and was significantly shorter than for group FC 5.14
      min (3.45-7.44), and for group CC 4.26 min (2.3-5.52) (95% CI 3.342-4.851), (P =
      .007). There was no significant difference between bursting pressures of group S
      (91.67 +/- 15.41 mmHg, 95% CI 79.82-103.5) compared with group FC (119.4 +/-
      40.03 mmHg, 95% CI 88.67-150.2) (P = .160) and compared with group CC (103.3 +/-
      32.31 mmHg, 95% CI 78.5-128.2) (P = .707) CONCLUSION: Hand-sewn techniques are
      effective but fairly demanding in terms of time. Skin staples are less time
      consuming, and resist pressures comparable to those resisted by handsewn
      techniques. For this reason, an SKS technique may be a valid option for
      typhlotomy closure in cattle.

PMID- 25998315
TI  - Animals in healthcare facilities: recommendations to minimize potential risks.

PMID- 25998316
TI  - Concurrent Acute Necrotizing Adenovirus Hepatitis and Enterocolitis in an Adult
      Patient After Double Cord Blood Stem Cell Transplant for Refractory Crohn's
      Disease.
AB  - It has been recently recognized that adenovirus is a pathogen with high morbidity
      and mortality among immunocompromised patients, particularly after solid organ or
      stem cell transplant. Confluent necrotizing hepatitis secondary to adenovirus
      infection alone or together with other organ involvement is extremely rare. There
      are only 32 cases of confluent necrotizing hepatitis reported in adults since
      1960 and most occur after iatrogenic immunosuppression for bone marrow or solid
      organ transplantation or in other states of immunosuppression, including acquired
      immunodeficiency syndrome or chemotherapy treatment. We present the first case of
      concurrent adenovirus-induced necrotizing hepatitis and enterocolitis in an adult
      patient after double cord stem cell transplant for refractory Crohn's disease.
      Additionally, we report the imaging and morphologic findings and discuss the
      potential significance of morphology and immunohistochemistry as a practical
      approach for identifying adenovirus. 

PMID- 25998317
TI  - Atypical Cellular Chorangioma: A Potential Diagnostic Pitfall With Worrisome
      Aspects but a Favorable Prognosis.
AB  - Chorangiomas are rather frequent neoplasms encountered on placental examination
      but in rare cases they present some worrisome histological features that could
      alarm the pathologist and be misinterpreted as a malignant neoplasm, even if
      their biological behavior is favorable. We describe an unusual chorangioma with
      high cellularity and abundant mitosis that, after careful examination and
      postpartum follow-up, showed benign clinical course for mother and child
      confirming previous reported cases. This type of tumor is known in the literature
      as atypical cellular chorangioma and its identification is important in order to
      exclude potentially dangerous overtreatment. 

PMID- 25998318
TI  - Spindle Cell Epithelioma of the Vagina: Report of Two Cases, Literature Review,
      and New Immunohistochemical Markers.
AB  - Spindle cell epitheliomas of the vagina are rare benign tumors of uncertain
      histogenesis. It has been hypothesized that they originate from a pluripotent
      cell population. Here, we report 2 cases of spindle cell epitheliomas of the
      vagina. Both patients presented with a painless vaginal nodule. The resected
      lesions were solid, well circumscribed, and composed of a proliferation of
      epithelioid or epithelial cells admixed with spindle cells without atypia. The 2
      cellular populations expressed epithelial and mesenchymal markers. Based on these
      morphologic and immunohistochemical findings, a diagnosis of spindle cell
      epithelioma was rendered in both cases. Furthermore, we describe for the first
      time the expression of WT-1 (Wilms' tumor protein 1) and calretinin in addition
      to the previously defined immunohistochemical profile. 

PMID- 25998319
TI  - The reduced Co(2+) -binding ability of ischaemia-modified albumin is unlikely to
      be because of oxidative modification of the N-terminus.

PMID- 25998320
TI  - Drug-drug interaction profile of components of a fixed combination of netupitant
      and palonosetron: Review of clinical data.
AB  - Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with
      serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced
      nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of
      netupitant (NETU)-a new NK1 RA-and PALO, is currently under development. In vitro
      data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor
      of P-glycoprotein (P-gp). This review evaluates potential drug-drug interactions
      between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates
      in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug
      when NETU was coadministered with PALO (single doses) and when single doses of
      NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY),
      midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors
      (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate
      (digoxin (DIG)). Results showed no relevant PK interactions between NETU and
      PALO. Coadministration of NETU increased MID and ERY exposure and significantly
      increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected.
      NEPA coadministration had no clinically significant effect on oral contraception,
      although levonorgestrel exposure increased. NETU exposure increased after
      coadministration of NEPA with KETO and decreased after coadministration with RIF;
      PALO exposure was unaffected. NETU coadministration did not influence DIG
      exposure. In conclusion, there were no clinically relevant interactions between
      NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and
      ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4
      inducers/inhibitors/substrates should be done with caution. Dose reduction is
      recommended for DEX. Dose adjustments are not needed for NETU coadministration
      with P-gp substrates. 

PMID- 25998321
TI  - Timing of birth: Parsimony favors strategic over dysregulated parturition.
AB  - OBJECTIVES: The "dysregulated parturition" narrative posits that the human stress
      response includes a cascade of hormones that "dysregulates" and accelerates
      parturition but provides questionable utility as a guide to understand or prevent
      preterm birth. We offer and test a "strategic parturition" narrative that not
      only predicts the excess preterm births that dysregulated parturition predicts
      but also makes testable, sex-specific predictions of the effect of stressful
      environments on the timing of birth among term pregnancies. METHODS: We use
      interrupted time-series modeling of cohorts conceived over 101 months to test for
      lengthening of early term male gestations in stressed population. We use an event
      widely reported to have stressed Americans and to have increased the incidence of
      low birth weight and fetal death across the country-the terrorist attacks of
      September 2001. We tested the hypothesis that the odds of male infants conceived
      in December 2000 (i.e., at term in September 2001) being born early as opposed to
      full term fell below the value expected from those conceived in the 50 prior and
      50 following months. RESULTS: We found that term male gestations exposed to the
      terrorist attacks exhibited 4% lower likelihood of early, as opposed to full or
      late, term birth. CONCLUSIONS: Strategic parturition explains observed data for
      which the dysregulated parturition narrative offers no prediction-the timing of
      birth among gestations stressed at term. Our narrative may help explain why
      findings from studies examining associations between population- and/or
      individual-level stressors and preterm birth are generally mixed.

PMID- 25998322
TI  - Authors reply.

PMID- 25998324
TI  - Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors.
AB  - BACKGROUND: Indoxyl sulfate is a protein-bound uremic toxin and its dialytic
      clearance is comparatively low. We propose a method to increase indoxyl sulfate
      dialytic clearance. METHODS: Human serum albumin, preloaded with indoxyl sulfate,
      was circulated on the blood side of an F40S dialyzer with single-pass counter
      current dialysate flow. Tryptophan or docosahexaenoic acid (DHA), which are
      binding competitors to indoxyl sulfate, were infused into the blood-side circuit
      upstream of the dialyzer, and their abilities to increase the removal of indoxyl
      sulfate determined. RESULTS: Baseline indoxyl sulfate removal was 10.2 +/- 0.3%,
      which increased to 18.5 +/- 0.4% with infusion of tryptophan (p < 0.001) and 27.7
      +/- 1.0% with infusion of DHA (p < 0.001). CONCLUSIONS: This study shows that
      tryptophan and DHA effectively increase indoxyl sulfate removal in an in vitro
      dialysis model. The concept of using binding competitors to enhance the clearance
      of protein-bound uremic toxins could be applied to current hemodialysis
      technology.

PMID- 25998323
TI  - Adverse events of local treatment in long-term head and neck rhabdomyosarcoma
      survivors after external beam radiotherapy or AMORE treatment.
AB  - BACKGROUND: Radiotherapy is a well-known cause of adverse events (AEs). To reduce
      AEs, an innovative local treatment was developed in Amsterdam: Ablative surgery,
      MOuld brachytherapy and surgical REconstruction (AMORE). AIMS: (1) to determine
      the prevalence of AEs in HNRMS survivors and (2) to compare AEs between survivors
      treated with the international standard: external beam radiotherapy (EBRT-based:
      London) and survivors treated with AMORE if feasible, otherwise EBRT (AMORE
      based: Amsterdam). METHODS: All HNRMS survivors, treated in London or Amsterdam
      between January 1990 and December 2010 (n = 153), and alive ? 2 years post
      treatment were eligible (n = 113). A predefined list of AEs was assessed in a
      multidisciplinary clinic and graded according to the Common Terminology Criteria
      for Adverse Events. RESULTS: Eighty HNRMS survivors attended the clinic (median
      follow-up 10.5 years); 63% experienced ? 1 severe or disabling event, and 76% had
      ? 5 AEs (any grade). Survivors with EBRT-based treatment were, after adjustment
      for site, age at diagnosis, and follow-up duration, at increased risk to develop
      any grade 3/4 event or ? 5 AEs (any grade) compared with survivors with AMORE
      based treatments (p = 0.032 and 0.01, respectively). Five year overall survival
      (source population) after EBRT-based treatment was 75.0%, after AMORE-based
      treatment 76.9%, p = 0.56. CONCLUSION: This study may serve as a baseline
      inventory and can be used in future studies for prospective assessments of AEs
      following the introduction of novel local treatment modalities. AMORE-based local
      treatment resulted in similar overall survival and a reduction of AEs secondary
      to local treatment.

PMID- 25998325
TI  - MP2 calculation of (77) Se NMR chemical shifts taking into account relativistic
      corrections.
AB  - The main factors affecting the accuracy and computational cost of the Second
      order Moller-Plesset perturbation theory (MP2) calculation of (77) Se NMR
      chemical shifts (methods and basis sets, relativistic corrections, and solvent
      effects) are addressed with a special emphasis on relativistic effects. For the
      latter, paramagnetic contribution (390-466 ppm) dominates over diamagnetic term
      (192-198 ppm) resulting in a total shielding relativistic correction of about 230
      260 ppm (some 15% of the total values of selenium absolute shielding constants).
      Diamagnetic term is practically constant, while paramagnetic contribution spans
      over 70-80 ppm. In the (77) Se NMR chemical shifts scale, relativistic
      corrections are about 20-30 ppm (some 5% of the total values of selenium chemical
      shifts). Solvent effects evaluated within the polarizable continuum solvation
      model are of the same order of magnitude as relativistic corrections (about 5%).
      For the practical calculations of (77) Se NMR chemical shifts of the medium-sized
      organoselenium compounds, the most efficient computational protocols employing
      relativistic Dyall's basis sets and taking into account relativistic and solvent
      corrections are suggested. The best result is characterized by a mean absolute
      error of 17 ppm for the span of (77) Se NMR chemical shifts reaching 2500 ppm
      resulting in a mean absolute percentage error of 0.7%.

PMID- 25998326
TI  - Stacked graphene platelet nanofibers dispersed in the liquid electrolyte of
      highly efficient cobalt-mediator-based dye-sensitized solar cells.
AB  - Stacked graphene platelet nanofibers (SGNF) dispersed in the electrolyte of dye
      sensitized solar cells (DSSCs) can efficiently improve the charge transport and
      catalytic reactions of the Co(iii)/(ii) redox couple so that the quinoxaline dye 
      based DSSC containing 0.2 mg mL(-1) SGNF exhibits the best power conversion
      efficiency (PCE) of 9.81%. 

PMID- 25998327
TI  - Nonmedical factors and the transfer of spine trauma patients initially evaluated
      at Level III and IV trauma centers.
AB  - BACKGROUND CONTEXT: The influence of nonmedical factors on the disposition of
      spine trauma patients, initially seen in less specialized institutions, remains
      an issue of debate. PURPOSE: To investigate the association of lack of insurance
      and African-American race with the probability of being transferred to a Level I
      or II trauma center, after being evaluated in the emergency department (ED) of
      Level III or IV trauma centers for spine trauma. STUDY DESIGN/SETTING: This was a
      retrospective cohort study. PATIENT SAMPLE: A total of 14,133 patients who were
      registered in National Trauma Data Bank (NTDB) from 2009 to 2011 and initially
      evaluated in the ED of Level III or IV trauma centers for spine trauma were
      included. OUTCOME MEASURES: The outcome measures were rates of transfer to a
      higher level of care trauma center. METHODS: We performed a retrospective cohort
      study involving spine trauma patients, who were registered in the NTDB between
      2009 and 2011. Regression techniques, controlling for clustering at the hospital
      level, were used to investigate the association of insurance status and race with
      the possibility of transfer. RESULTS: Overall, 4,142 patients (29.31%) were
      transferred to a higher level of care institution, and 9,738 (70.69%) were
      admitted to a Level III or IV trauma center. Multivariable logistic regression
      analysis demonstrated an association of uninsured patients with increased
      possibility of transfer (odds ratio [OR], 1.40; 95% confidence interval [CI],
      1.22-1.61). This persisted after using a mixed effects model to control for
      clustering at the hospital level (OR, 1.65; 95% CI, 1.37-1.96). African-American
      race was not associated with the decision to transfer, when using a mixed effects
      model (OR, 1.15; 95% CI, 0.89-1.48). However, African-Americans with Glasgow Coma
      Scale greater than 8 (OR, 1.40; 95% CI, 1.13-1.74) or Injury Severity Score less
      than 15 (OR, 1.54; 95% CI, 1.21-1.96) were associated with a higher likelihood of
      transfer. CONCLUSIONS: In summary, lack of insurance was associated with
      increased possibility of transfer to higher level of care institutions, after
      evaluation in a Level III or IV trauma center ED for spine trauma. The same was
      true for African-Americans with milder injuries.

PMID- 25998328
TI  - Circulatory dynamics of the cauda equina in lumbar canal stenosis using dynamic
      contrast-enhanced magnetic resonance imaging.
AB  - BACKGROUND CONTEXT: There has been no study regarding the cauda equina
      circulation of patients with neurogenic intermittent claudication (NIC) in lumbar
      spinal canal stenosis (LSCS) using dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI). PURPOSE: The mechanism responsible for the onset of NIC was
      investigated using DCE-MRI to examine changes in cauda equina blood flow in
      patients with LSCS. STUDY DESIGN: This was a retrospective longitudinal registry
      and magnetic resonance imaging study. PATIENT SAMPLE: The subjects consisted of
      23 patients who had LSCS associated with NIC (stenosis group). Ten asymptomatic
      volunteers who did not have NIC served as controls (control group). In the LSCS
      group, the cross-sectional area of the dural sac was <75 mm2 at the site of most
      severe stenosis. These patients were further divided into single and double
      stenosis subgroups. OUTCOME MEASURES: The main measures we used were the signal
      intensity (S-I) ratio and the shape and size of the time intensity (T-I) curves.
      We compared these between the stenosis and control groups. METHODS: At first,
      plain T1-weighted MR images were obtained and the lumbar dural sac cross
      sectional area was measured using a digitizer. For DCE-MRI, sagittal T1-weighted
      images of the same slice were acquired continuously for 10 minutes after
      administration of gadolinium as an intravenous bolus to observe the distribution
      of contrast medium (gadolinium) in the cauda equina. To objectively evaluate
      changes in contrast enhancement of the cauda equina at the site of canal
      stenosis, regions of interest were established. The signal intensity (SI) ratio
      was calculated to compare the signal intensities before and after contrast
      enhancement, and time-intensity curves were prepared to investigate changes over
      time. RESULTS: The static imaging findings and the changes of gadolinium uptake
      showed striking differences between the study and control patients. In the
      stenosis group, abnormal intrathecal enhancement showed around the site of
      stenosis on enhanced MR imaging. The SI ratio at the site of canal stenosis had a
      slower increase in the arterial phase when compared with that in the control
      group and remained high in the venous phase for up to 10 minutes. Finally,
      abnormal intrathecal enhancement was visible around the site of stenosis on
      enhanced MR imaging in all patients. CONCLUSIONS: These clinical data indicate
      that cauda equina nerve roots in the LSCS patients are pathologic even when
      symptoms are not elicited in the supine position, suggesting that intraradicular
      venous congestion and edema themselves do not influence the existence of
      radicular symptoms.

PMID- 25998329
TI  - Sir, it is my opinion that...

PMID- 25998330
TI  - Implant checklist.

PMID- 25998332
TI  - Dental regulation: Burden impacting patients.

PMID- 25998331
TI  - Safety in practice: Sharps injuries.

PMID- 25998333
TI  - Behcet disease: A new therapeutic agent. [corrected].

PMID- 25998334
TI  - Conference report: What we learned at #BDA2015.

PMID- 25998335
TI  - Leading healthcare professionals call for safer delivery of sedation for dental
      patients.

PMID- 25998336
TI  - WW1 dentures identified by BDA.

PMID- 25998337
TI  - Penis worm dragged itself round by its teeth!

PMID- 25998339
TI  - FGDP(UK) launches new initiative.

PMID- 25998340
TI  - Negative experiences 'stressful for teeth'.

PMID- 25998344
TI  - Around the world.

PMID- 25998341
TI  - 'Safeguarding' becomes recommended CPD.

PMID- 25998345
TI  - Gel filling could aid bone growth.

PMID- 25998346
TI  - Deployment of a dental treatment facility during Operation Gritrock - lessons for
      future maritime contingency operations.
AB  - Following the largest outbreak of Ebola in history, Royal Fleet Auxiliary Argus
      deployed to Sierra Leone in October 2014 as part of the UK Armed Forces response
      to the Ebola crisis. Integral to the Primary Casualty Receiving Facility
      deployment was a dental capability, which was one of the busiest departments on
      board during the deployment. This paper describes the deployment and unique
      challenges of conducting dental treatment in an environment where there is an
      infectious disease epidemic. 

PMID- 25998350
TI  - An audit of the use of intravenous ketamine for paediatric dental conscious
      sedation.
AB  - AIM: An audit of the use of intravenous ketamine for the provision of conscious
      sedation in paediatric dentistry was carried out over a three-year period. AUDIT
      DESIGN: In the audit, 3,751 children were treated and an evaluation was carried
      out for safety and effectiveness of the drug and procedure, the quality of
      sedation and clinical procedures provided. In addition, the occurrence of any
      adverse effects and parental satisfaction were noted along with recovery. All
      children were ASA I and II, with an average age of 7.5 years. Children were
      referred because of management problems and were assessed to be at the high
      anxious level of four and five on the Venham scale. A weight related 0.25 mg/kg
      was initially administered with additional increments of 0.25 mg/kg given if
      required. The average total dose provided was 0.41 mg/kg. RESULTS: The majority
      of children (76%) accepted all treatment with no problems, with 19% experiencing
      a small amount of resistance. Although a range of dental treatment was provided,
      it was mostly exodontias of carious primary dentition. A 27% response was
      provided assessing satisfaction which was very favourable. No adverse reactions
      occurred although the most common postoperative experience was nausea.
      CONCLUSION: This audit demonstrated the safety and effectiveness of using
      intravenous ketamine for paediatric conscious sedation and implications for
      training and appropriate service delivery were discussed.

PMID- 25998351
TI  - Assessment of efficacy and post-bleaching sensitivity of home bleaching using 10%
      carbamide peroxide in extended and non-extended bleaching trays.
AB  - AIM: This study aimed to compare the effect of extended margin and conventional
      bleaching trays on tooth bleaching and tooth sensitivity. METHOD AND METHODS:
      Twenty subjects (18-56 years) were investigated in a split arch design clinical
      study that was conducted in a general dental practice. Each subject received a
      custom made bleaching tray and 10% carbamide peroxide gel. The bleaching trays
      had the borders extended 5 mm beyond the gingival margins on the right side and
      finished just at the gingival margin on the left side. Shade change and tooth
      sensitivity were the primary outcomes studied and analysed in this study. The
      shade of the six upper and lower anterior teeth was assessed using a value
      ordered shade guide before, one week and two weeks after treatment. Sensitivity
      was self-assessed using a visual analogue scale (VAS) at the end of the first and
      second weeks of the study. RESULTS: At the end of week two, the mean shade change
      was 5.01 (+/- 3.37) and 5.10 (+/- 3.36) for teeth covered by extended and non
      extended tray design, respectively. The mean VAS sensitivity scores for teeth
      covered by extended and non-extended tray design were 0.96 (+/- 1.39) and 0.66
      (+/- 0.96), respectively. There was no significant statistical difference between
      the two designs at any assessment point with regard to shade change and
      sensitivity (p >0.05). CONCLUSIONS: It can be concluded that an extended tray
      design confers no superior effect in terms of the whitening outcome achieved or
      in reducing levels of sensitivity. Thus, both tray designs can be used depending
      on a dentist's personal preference.

PMID- 25998352
TI  - Patient-clinician communication in a dental setting: a pilot study.
AB  - OBJECTIVE: To undertake a pilot study and examine whether the communication
      assessment tool (CAT) is useful in assessing patient perceptions of dentists'
      interpersonal skills. DESIGN: Cross-sectional questionnaire study. SETTING: Three
      speciality dental clinics in a University teaching hospital in the United
      Kingdom. PARTICIPANTS, MATERIALS AND MEASURES: One hundred patients, seen by 20
      dentists, were recruited to the study. Patients completed the CAT after their
      consultation. MAIN OUTCOME MEASURES: Patient ratings of excellent interpersonal
      skills within a dental consultation according to dentists' experience, gender and
      speciality. RESULTS: Complete data was received from 95 patients. On average,
      dentists' communication skills were rated as excellent 73% of the time. Patients
      were least satisfied with opportunities to ask questions within their
      consultation and with their level of involvement in decision-making. There were
      suggested differences in patients' perceived satisfaction with communication
      according to dentists' experience and gender. CONCLUSION: Overall, patients are
      satisfied with the quality of communication with their dentist. Our findings are
      comparable to those from larger studies suggesting that the CAT is an effective
      tool to use in a dental context. The CAT would be useful in documenting the
      development of dentists' and students' interpersonal skills.

PMID- 25998353
TI  - Professional behaviours demonstrated by undergraduate dental students using an
      incident reporting system.
AB  - Critical incident reporting is widely used across healthcare and other sectors
      for reporting adverse events or behaviours. More recently it has been used in
      medical education as a means of assessing student professionalism. The aims of
      this study were to determine the usage of critical incident forms when reporting
      behaviours related to professionalism demonstrated by undergraduate dental
      students, and the types of behaviours exhibited. Three types of form could be
      awarded for highly professional (green), minor unprofessional (yellow) and
      serious unprofessional (red) behaviours. All forms completed over a two-year
      period were analysed recording the year of student, type of card and demographic
      of the member of staff reporting the incident. All text relating to the nature of
      the incident was entered into a qualitative data analysis software package and
      analysed thematically. In total, 583 cards were awarded, 55% green, 34% yellow
      and 11% red. Seventy-four percent of cards were awarded in a clinical
      environment, with administrative staff using them the most (29%). The
      overwhelming professional behaviours demonstrated related to altruism. The most
      common unprofessional behaviours related to a lack of conscientiousness, although
      a greater range of common unprofessional behaviours were reported. In conclusion,
      critical incidents forms were widely used for reporting both professional and
      unprofessional behaviours particularly in clinical environments by a range of
      staff. Such forms may be a valuable addition to the professionalism assessment
      portfolio, capturing behaviours not previously reported using traditional
      methods. 

PMID- 25998354
TI  - The role of stereopsis (three-dimensional vision) in dentistry: review of the
      current literature.
AB  - Clinical dental work is placing increasing demands on a clinician's vision as new
      techniques that require fine detail become more common. High hand-eye
      coordination requires good visual acuity as well as other psychological and
      neurological qualities such as stereopsis. Stereopsis (three-dimensional vision)
      is the highest form of depth perception obtained by visual disparity of images
      formed in the retinas of two eyes. It is believed to confer functional benefits
      on everyday tasks such as hand-eye coordination. Although its role in depth
      perception has long been established, little is known regarding the importance of
      stereopsis in dentistry. This article reviews the role of stereopsis in everyday
      life and the available literature on the importance of stereopsis in dentistry. 

PMID- 25998369
TI  - Robin M. Davies.

PMID- 25998370
TI  - Brian Holmes.

PMID- 25998371
TI  - Pathological polyploidy in liver disease.

PMID- 25998372
TI  - Endovascular stenting of mesenterico-portal vein stenosis to reduce blood flow
      through venous collaterals prior to pancreatoduodenectomy.
AB  - BACKGROUND: When the mesenterico-portal vein is stenosed due to tumor related
      compression, venous collaterals develop and flow occurs antegrade towards the
      portal vein through the collateral tributaries. Undertaking pancreatoduodenectomy
      for pancreatic cancer in this setting may result in significant blood loss during
      the process of ligation of these tributaries. DESCRIPTION OF TECHNIQUE: We
      describe the technique of endovascular stenting of the mesenterico-portal vein to
      reduce flow within these collateral tributaries and hence blood loss, to
      facilitate extended pancreatoduodenectomy and vein resection. CONCLUSION:
      Percutaneous transhepatic placement of endovascular stent into a stenotic
      mesentero-portal vein facilitates pancreatoduodenectomy by reducing operative
      time, which would otherwise be required in dealing with the extensive venous
      collaterals and hence also reducing blood loss.

PMID- 25998373
TI  - Why is Anatase a Better Photocatalyst than Rutile? The Importance of Free
      Hydroxyl Radicals.
AB  - A tale of two polymorphs: Anatase is typically a more effective photocatalyst
      than rutile, however no consensus exists upon the reasons for this difference.
      Highlighted is a recent development in this area, which gives new insight into
      the desorption of reactive species from the surface of anatase and rutile.
      Following presentation of key methods and results of the highlighted work, the
      wider implications to other similar semiconductor photocatalysts are considered. 

PMID- 25998375
TI  - Regorafenib: A Review of Its Use in Patients with Advanced Gastrointestinal
      Stromal Tumours.
AB  - Regorafenib (Stivarga((r))) is an orally administered small molecule inhibitor of
      multiple protein kinases, including kinases involved in oncogenesis and tumour
      angiogenesis. It was initially approved for use in patients with previously
      treated metastatic colorectal cancer. Based on the findings of the phase III GRID
      clinical trial, approval for regorafenib has been expanded to include the
      treatment of advanced gastrointestinal stromal tumours (GISTs) following the
      failure of imatinib and sunitinib. In the GRID trial, regorafenib significantly
      improved progression-free survival and was associated with a significantly higher
      disease control rate than placebo. No significant between-group difference was
      observed in overall survival (OS) in the trial; however, the high proportion of
      patients who crossed over from placebo to regorafenib likely impacted the OS
      analysis. Regorafenib has an acceptable tolerability profile, with most adverse
      events being manageable with dose modification and/or supportive measures. The
      most commonly reported drug-related adverse events among patients receiving
      regorafenib in the GRID trial were hand-foot skin reaction, hypertension,
      diarrhoea and fatigue. In conclusion, regorafenib presents a valuable new tool in
      the treatment of patients with advanced GISTs following the failure of imatinib
      and sunitinib. 

PMID- 25998376
TI  - Fabrication of CdMoO4@CdS core-shell hollow superstructures as high performance
      visible-light driven photocatalysts.
AB  - CdMoO4@CdS core-shell hollow microspheres with the diameter of 2-3 MUm were
      synthesized through a simple ion exchange hydrothermal method by using CdMoO4
      solid microspheres as the sacrificial template in the presence of thioacetamide
      (TAA). Based on the detailed investigation it was found that the concentration of
      TAA in the starting solution affects the size of the CdS nanosheets and the
      hollowing process. At the TAA concentration of 0.1 M, CdMoO4@CdS core-shell
      hollow spheres with a CdS nanosheet thickness of 50-100 nm were obtained. The
      formed CdS nanosheets have a hexagonal wurtzite structure and exhibit good size
      uniformity and regularity. Furthermore, the photocatalytic activity of the as
      prepared samples was evaluated towards degradation of Rhodomine B (RhB) aqueous
      dye solution under visible-light. Compared to CdMoO4 microspheres, CdMoO4@CdS
      core-shell hollow microspheres show enhanced photocatalytic activity. The
      observed photocatalytic performance was attributed to the synergetic effects of
      composite morphology, pore structure, and exposed two-dimensional (2D) CdS
      nanosheets with dominant 001 facets in CdMoO4@CdS core-shell hollow microspheres.
      Furthermore, the growth mechanism of CdMoO4@CdS hollow microspheres was discussed
      in detail. 

PMID- 25998374
TI  - Use of Non-Vitamin K Antagonist Oral Anticoagulants in Special Patient
      Populations with Nonvalvular Atrial Fibrillation: A Review of the Literature and
      Application to Clinical Practice.
AB  - Atrial fibrillation is a commonly encountered arrhythmia associated with
      increased risk for thromboembolic events. Anticoagulation is necessary to
      decrease the risk of ischemic stroke. Traditionally, warfarin has been the only
      oral pharmacotherapeutic option for long-term anticoagulation in patients with
      nonvalvular atrial fibrillation (NVAF). Recently, non-vitamin K antagonist oral
      anticoagulants (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban,
      have become available as alternatives for warfarin in the prevention of stroke in
      patients with NVAF. Recently published atrial fibrillation guidelines contain new
      recommendations for risk stratification tools in determining the need for
      anticoagulant therapy and incorporate NOAC pharmacotherapy options for stroke
      prevention in patients with NVAF. NOACs offer several advantages over warfarin,
      including the elimination of routine laboratory monitoring, fewer drug and food
      interactions, and rapid therapeutic onset and offset. However, the lack of
      antidote in the case of serious bleeding and lack of data for long-term use in
      patient populations at risk for bleeding is problematic. Older adults are at high
      risk for thromboembolic and bleeding events as a result of anticoagulation and
      require special consideration when selecting anticoagulant therapy. The risk of
      drug accumulation and bleeding is concerning in the presence of renal impairment.
      The objective of this review is to provide the clinician with an update on the
      use of NOACs for NVAF, focusing on older adults and patients with renal
      impairment in light of recently published atrial fibrillation guidelines.
      Available data on using NOACs in coronary artery stenting, cardioversion, and
      ablation are also reviewed. 

PMID- 25998377
TI  - Validation of the simplified Chinese (Mainland) version of the Disability of the
      Arm, Shoulder, and Hand questionnaire (DASH-CHNPLAGH).
AB  - BACKGROUND: We developed a simplified Chinese version of the Disabilities of the
      Arm, Shoulder, and Hand (DASH) questionnaire (shorthand for DASH-CHNPLAGH) by
      conducting cross-cultural adaptation and evaluating its reliability and validity.
      METHODS: Both the forward and back translations were performed by language
      officers and medical professionals from different fields to translate the
      original DASH version into the DASH-CHNPLAGH version with minimized culture
      discrepancies. A total of 300 patients with upper extremity disorders were
      recruited to complete two DASH-CHNPLAGH questionnaires with 3-week test interval
      time. RESULTS: The intraclass coefficient (ICC) and Cronbach's alpha for the 30
      item disability/symptom of the DASH-CHNPLAGH was 0.94 and 0.96, respectively,
      which were relatively high among that reported in previous literatures. DASH
      CHNPLAGH showed a positive correlation with a visual analogue scale (VAS) and a
      negative correlation with SF-36 items. CONCLUSION: The simple Chinese version of
      DASH is a reliable and valid measurement for patients with upper extremity
      problems.

PMID- 25998379
TI  - Electronic cigarettes and nicotine dependence: evolving products, evolving
      problems.
AB  - Electronic cigarettes (ECIGs) use an electric heater to aerosolize a liquid that
      usually contains propylene glycol, vegetable glycerin, flavorants, and the
      dependence-producing drug nicotine. ECIG-induced nicotine dependence has become
      an important concern, as some ECIGs deliver very little nicotine while some may
      exceed the nicotine delivery profile of a tobacco cigarette. This variability is
      relevant to tobacco cigarette smokers who try to switch to ECIGs. Products with
      very low nicotine delivery may not substitute for tobacco cigarettes, so that
      ECIG use is accompanied by little reduced risk of cigarette-caused disease.
      Products with very high nicotine delivery may make quitting ECIGs particularly
      difficult should users decide to try. For non-smokers, the wide variability of
      ECIGs on the market is especially troublesome: low nicotine products may lead
      them to initiate nicotine self-administration and progress to higher dosing ECIGs
      or other products, and those that deliver more nicotine may produce nicotine
      dependence where it was not otherwise present. External regulatory action, guided
      by strong science, may be required to ensure that population-level nicotine
      dependence does not rise. 

PMID- 25998380
TI  - P7, a novel antagonist of corticotropin releasing factor receptor type 1 (CRFR1)
      screened from phage display library.
AB  - The corticotropin releasing factor (CRF) plays a central role in regulating the
      activities of hypothalamic-pituitary-adrenal (HPA) axis in the presence of a
      variety of stressful stimuli via binding to its type 1 receptors (CRFR1). Despite
      that many peptidic or non-peptidic antagonists of CRFR1 have been developed to
      serve as therapeutic tools to CRF-related pathologies, none of them have been
      utilized clinically. Targeting the extracellular domain 1 (EC1) of CRFR1, the CRF
      binding site, represents a new strategy to inhibit the function of the receptor.
      However, no such agents have been identified up to now. Herein, by using an 87
      amino acid fragment corresponding to the EC1 region as the bait, we screened the
      binding polypeptides from a phage display (Ph.D.-12) peptide library. After 3
      round biopanning, positive clones were selected and the polypeptides carried by
      them were identified. 5 polypeptides were found to bind with the target
      specifically. Among them, the P7 exhibited the highest affinity. By evaluating
      the cAMP accumulation in the CRFR1 or CRFR2-expressing HEK293 cells, we
      demonstrated that P7 blocking the function of CRFR1, but not CRFR2. In addition,
      we also found that P7 and CRF act on CRFR1 competitively. Taken together, we
      reveal that P7, a novel polypeptide identified from phage display library,
      inhibits the function of CRFR1 effectively and specifically by binding at its EC1
      domain. The new polypeptide might provide a promising agent for diagnostic or
      therapeutic utilities in CRF-related disorders. 

PMID- 25998381
TI  - MEK5 suppresses osteoblastic differentiation.
AB  - Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen
      activated protein kinase (MAPK) family and is activated by its upstream kinase,
      MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of
      MEK5 has been investigated in several fields, little is known about its role in
      osteoblastic differentiation. In this study, we have demonstrated the role of
      MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and
      bone marrow stromal ST2 cells. We found that treatment with BIX02189, an
      inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene
      expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the
      calcification of the extracellular matrix. Moreover, osteoblastic cell
      proliferation decreased at a concentration of greater than 0.5 MUM. In addition,
      knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene
      expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type
      MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers
      including ALP, OCN and osterix, but promoted cell proliferation. In summary, our
      results indicated that MEK5 suppressed the osteoblastic differentiation, but
      promoted osteoblastic cell proliferation. These results implied that MEK5 may
      play a pivotal role in cell signaling to modulate the differentiation and
      proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts
      may be of potential use in the treatment of osteoporosis.

PMID- 25998378
TI  - Efficient Exploration of Membrane-Associated Phenomena at Atomic Resolution.
AB  - Biological membranes constitute a critical component in all living cells. In
      addition to providing a conducive environment to a wide range of cellular
      processes, including transport and signaling, mounting evidence has established
      active participation of specific lipids in modulating membrane protein function
      through various mechanisms. Understanding lipid-protein interactions underlying
      these mechanisms at a sufficiently high resolution has proven extremely
      challenging, partly due to the semi-fluid nature of the membrane. In order to
      address this challenge computationally, multiple methods have been developed,
      including an alternative membrane representation termed highly mobile membrane
      mimetic (HMMM) in which lateral lipid diffusion has been significantly enhanced
      without compromising atomic details. The model allows for efficient sampling of
      lipid-protein interactions at atomic resolution, thereby significantly enhancing
      the effectiveness of molecular dynamics simulations in capturing membrane
      associated phenomena. In this review, after providing an overview of HMMM model
      development, we will describe briefly successful application of the model to
      study a variety of membrane processes, including lipid-dependent binding and
      insertion of peripheral proteins, the mechanism of phospholipid insertion into
      lipid bilayers, and characterization of optimal tilt angle of transmembrane
      helices. We conclude with practical recommendations for proper usage of the model
      in simulation studies of membrane processes. 

PMID- 25998382
TI  - MRI measurement of blood-brain barrier transport with a rapid acquisition
      refocused echo (RARE) method.
AB  - Dynamic Contrast Enhanced (DCE) MRI is increasingly being used to assess changes
      in capillary permeability. Most quantitative techniques used to measure capillary
      permeability are based on the Fick equation that requires measurement of signal
      reflecting both plasma and tissue concentrations of the solute being tested. To
      date, most Magnetic Resonance Imaging (MRI) methods for acquiring appropriate
      data quickly rely on gradient recalled echo (GRE) type acquisitions, which work
      well in clinical low field settings. However, acquiring this type of data on high
      field small animal preclinical MRIs is problematic due to geometrical distortions
      from susceptibility mismatch. This problem can be exacerbated when using small
      animal models to measure blood brain barrier (BBB) permeability, where precise
      sampling from the superior sagittal sinus (SSS) is commonly used to determine the
      plasma concentration of the contrast agent. Here we present results demonstrating
      that a standard saturation recovery rapid acquisition refocused echo (RARE)
      method is capable of acquiring T1 maps with good spatial and temporal resolution
      for Patlak analysis (Patlak, 1983) to assess changes in BBB Gd-DTPA permeability
      following middle cerebral artery occlusion with reperfusion in the rat. This
      method limits known problems with magnetic susceptibility mismatch and may thus
      allow greater accuracy in BBB permeability measurement in small animals. 

PMID- 25998383
TI  - Cooperative and selective roles of the WW domains of the yeast Nedd4-like
      ubiquitin ligase Rsp5 in the recognition of the arrestin-like adaptors Bul1 and
      Bul2.
AB  - The ubiquitin ligase Rsp5, which is the only yeast Saccharomyces cerevisiae
      member of the Nedd4-family, recognizes and ubiquitinates various substrate
      proteins through the functions of three conserved WW domains. To elucidate the
      role of each WW domain in endocytosis of the general amino acid permease Gap1 via
      interaction with the arrestin-like adaptor proteins Bul1 and Bul2 (Bul1/2), we
      investigated the effects of the double mutations that abrogate the recognition of
      PY motifs on target proteins (rsp5(W257F/P260A), rsp5(W359F/P362A), and
      rsp5(W415F/P418A)) and the alanine substitutions of the conserved threonine
      residues that are regarded as putative phosphorylation sites (rsp5(T255A),
      RSP5(T357A), and rsp5(T413A)), both of which are located within each WW domain.
      The rsp5(W257F/P260A), rsp5(W359F/P362A), and rsp5(W415F/P418A) mutations
      increased sensitivity to the proline analog azetidine-2-carboxylate (AZC),
      defective endocytosis of Gap1, and impaired interactions with Bul1. These results
      demonstrate that molecular recognition by each WW domain is responsible for the
      cooperative interaction with Bul1. Intriguingly, the RSP5(T357A) mutation
      enhanced AZC tolerance and endocytosis of Gap1, although rsp5(T255A) and
      rsp5(T413A) decreased both of them. While rsp5(T255A), RSP5(T357A), and
      rsp5(T413A) impaired the interaction of Rsp5 with Bul1, the RSP5(T357A) mutation
      specifically augmented the interaction with Bul2. The AZC tolerance enhanced by
      RSP5(T357A) was fully abolished by combining with each of the rsp5(W257F/P260A),
      rsp5(W359F/P362A), or rsp5(W415F/P418A) mutations. It was thus suggested that
      Thr357 in the WW2 domain has a unique role in preventing from the constitutive
      activation of Bul1/2-mediated endocytosis of Gap1. Taken together, our results
      highlight the cooperative and specific roles of WW domains in the regulation of
      Bul1/2-mediated cellular events. 

PMID- 25998384
TI  - EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-kappaB.
AB  - Non-small-cell lung cancer (NSCLC) is a severe disease threatening human health.
      Targeted therapy of epidermal growth factor receptor (EGFR)-tyrosine kinase
      inhibitors (TKIs) has obtained potent efficacy in the treatment of NSCLC
      patients. However, the effects of EGFR-TKIs on tumor immune microenvironment are
      unclear. In this study, we show that NSCLCs with EGFR mutation express higher
      programmed cell death ligand 1 (PD-L1) than NSCLCs with wild type EGFR. The EGFR
      activation is also associated with high expression of PD-L1. The EGFR-TKI
      gefitinib can reduce PD-L1 expression, via inhibiting NF-kappaB, in EGFR mutant
      NSCLC in vitro and in vivo. These findings elucidate a novel anti-tumor mechanism
      of EGFR-TKI and provide the possibility of combined strategy of targeted therapy
      and immunotherapy for EGFR mutant NSCLC patients. 

PMID- 25998385
TI  - Characterization of DNA binding and pairing activities associated with the native
      SFPQ.NONO DNA repair protein complex.
AB  - Nonhomologous end joining (NHEJ) is a major pathway for repair of DNA double
      strand breaks. We have previously shown that a complex of SFPQ (PSF) and NONO
      (p54(nrb)) cooperates with Ku protein at an early step of NHEJ, forming a
      committed preligation complex and stimulating end-joining activity by 10-fold or
      more. SFPQ and NONO show no resemblance to other repair factors, and their
      mechanism of action is uncertain. Here, we use an optimized microwell-based assay
      to characterize the in vitro DNA binding behavior of the native SFPQ.NONO complex
      purified from human (HeLa) cells. SFPQ.NONO and Ku protein bind independently to
      DNA, with little evidence of cooperativity and only slight mutual interference at
      high concentration. Whereas Ku protein requires free DNA ends for binding,
      SFPQ.NONO does not. Both Ku and SFPQ.NONO have pairing activity, as measured by
      the ability of DNA-bound protein to capture a second DNA fragment in a microwell
      based assay. Additionally, SFPQ.NONO stimulates DNA-dependent protein kinase
      autophosphorylation, consistent with the ability to promote formation of a
      synaptic complex formation without occluding the DNA termini proper. These
      findings suggest that SFPQ.NONO promotes end joining by binding to internal DNA
      sequences and cooperating with other repair proteins to stabilize a synaptic pre
      ligation complex. 

PMID- 25998386
TI  - mTOR is necessary for proper satellite cell activity and skeletal muscle
      regeneration.
AB  - The serine/threonine kinase mammalian target of rapamycin (mTOR) is a key
      regulator of protein synthesis, cell proliferation and energy metabolism. As
      constitutive deletion of Mtor gene results in embryonic lethality, the function
      of mTOR in muscle stem cells (satellite cells) and skeletal muscle regeneration
      remains to be determined. In this study, we established a satellite cell specific
      Mtor conditional knockout (cKO) mouse model by crossing Pax7(CreER) and
      Mtor(flox/flox) mice. Skeletal muscle regeneration after injury was severely
      compromised in the absence of Mtor, indicated by increased number of necrotic
      myofibers infiltrated by Evans blue dye, and reduced number and size of
      regenerated myofibers in the Mtor cKO mice compared to wild type (WT)
      littermates. To dissect the cellular mechanism, we analyzed satellite cell
      derived primary myoblasts grown on single myofibers or adhered to culture plates.
      The Mtor cKO myoblasts exhibited defective proliferation and differentiation
      kinetics when compared to myoblasts derived from WT littermates. At the mRNA and
      protein levels, the Mtor cKO myoblasts expressed lower levels of key myogenic
      determinant genes Pax7, Myf5, Myod, Myog than did the WT myoblasts. These results
      suggest that mTOR is essential for satellite cell function and skeletal muscle
      regeneration through controlling the expression of myogenic genes. 

PMID- 25998387
TI  - DDA3 targets Cep290 into the centrosome to regulate spindle positioning.
AB  - The centrosome is an important cellular organelle which nucleates microtubules
      (MTs) to form the cytoskeleton during interphase and the mitotic spindle during
      mitosis. The Cep290 is one of the centrosomal proteins and functions in cilia
      formation. Even-though it is in the centrosome, the function of Cep290 in mitosis
      had not yet been evaluated. In this study, we report a novel function of Cep290
      that is involved in spindle positioning. Cep290 was identified as an interacting
      partner of DDA3, and we confirmed that Cep290 specifically localizes in the
      mitotic centrosome. Depletion of Cep290 caused a reduction of the astral spindle,
      leading to misorientation of the mitotic spindle. MT polymerization also
      decreased in Cep290-depleted cells, suggesting that Cep290 is involved in spindle
      nucleation. Furthermore, DDA3 stabilizes and transports Cep290 to the centrosome.
      Therefore, we concluded that DDA3 controls astral spindle formation and spindle
      positioning by targeting Cep290 to the centrosome. 

PMID- 25998389
TI  - Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the
      alpha2,3 sialylation linkage of mammalian glycoproteins.
AB  - In this research, we examined which genes are involved in N-linked sialylation in
      Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. Three genes
      from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as
      knockdown targets with siRNA applied to reduce their expression. Single, double
      and triple gene knockdowns were investigated, and the reduction levels of
      sialylation on the total cell lysate were monitored by enzyme-linked lectin
      absorption assays (ELLA) and sialic acid quantification with high performance
      liquid chromatography (HPLC). All transfection groups showed effective reduction
      in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA
      transfection outweighed both the dual siRNA groups and single siRNA transfection
      groups. Next, this transfection approach was applied to CHO cells producing
      erythropoietin (EPO). Quantification of EPO sialylation showed similar result to
      total cell lysate except that the ST3GAL4 siRNA transfection exhibited the
      largest reduction according to the HPLC analysis as compared with other single
      siRNA transfections. Finally, the N-glycan released from the EPO transfected with
      ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single
      siRNA transfections. From these experiments, we concluded that each of these
      three genes were involved in N-linked sialylation and ST3GAL4 may play the
      critical role in glycoprotein sialylation of recombinant proteins such as EPO. 

PMID- 25998388
TI  - Hemin activation of innate cellular response blocks human immunodeficiency virus
      type-1-induced osteoclastogenesis.
AB  - The normal skeletal developmental and homeostatic process termed
      osteoclastogenesis is exacerbated in numerous pathological conditions and causes
      excess bone loss. In cancer and HIV-1-infected patients, this disruption of
      homeostasis results in osteopenia and eventual osteoporesis. Counteracting the
      factors responsible for these metabolic disorders remains a challenge for
      preventing or minimizing this co-morbidity associated with these diseases. In
      this report, we demonstrate that a hemin-induced host protection mechanism not
      only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti
      osteoclastogenic activity for non-infected cells. Since the mode of action of
      hemin is both physiological and pharmacological through induction of heme
      oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed
      therapeutic used to treat another disease, our study suggests an approach to
      developing novel, safe and effective therapeutic strategies for treating bone
      disorders, because hemin administration in humans has previously met required FDA
      safety standards. 

PMID- 25998391
TI  - Drosophila peptidyl-prolyl isomerase Pin1 modulates circadian rhythms via
      regulating levels of PERIOD.
AB  - In animal circadian clock machinery, the phosphorylation program of PERIOD (PER)
      leads to the spatio-temporal regulation of diverse PER functions, which are
      crucial for the maintenance of ~24-hr circadian rhythmicity. The peptidyl-prolyl
      isomerase PIN1 modulates the diverse functions of its substrates by inducing
      conformational changes upon recognizing specific phosphorylated residues. Here,
      we show that overexpression of Drosophila pin1, dodo (dod), lengthens the
      locomotor behavioral period. Using Drosophila S2 cells, we demonstrate that Dod
      associates preferentially with phosphorylated species of PER, which delays the
      phosphorylation-dependent degradation of PER. Consistent with this, PER protein
      levels are higher in flies overexpressing dod. Taken together, we suggest that
      Dod plays a role in the maintenance of circadian period by regulating PER
      metabolism.

PMID- 25998390
TI  - Ectopic expression of anti-HIV-1 shRNAs protects CD8(+) T cells modified with
      CD4zeta CAR from HIV-1 infection and alleviates impairment of cell proliferation.
AB  - Chimeric antigen receptors (CARs) are artificially engineered receptors that
      confer a desired specificity to immune effector T cells. As an HIV-1-specific
      CAR, CD4zeta CAR has been extensively tested in vitro as well as in clinical
      trials. T cells modified with this CAR mediated highly potent anti-HIV-1
      activities in vitro and were well-tolerated in vivo, but exerted limited effects
      on viral load and reservoir size due to poor survival and/or functionality of the
      transduced cells in patients. We hypothesize that ectopic expression of CD4zeta
      on CD8(+) T cells renders them susceptible to HIV-1 infection, resulting in poor
      survival of those cells. To test this possibility, highly purified CD8(+) T cells
      were genetically modified with a CD4zeta-encoding lentiviral vector and infected
      with HIV-1. CD8(+) T cells were vulnerable to HIV-1 infection upon expression of
      CD4zeta as evidenced by elevated levels of p24(Gag) in cells and culture
      supernatants. Concurrently, the number of CD4zeta-modified CD8(+) T cells was
      reduced relative to control cells upon HIV-1 infection. To protect these cells
      from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed
      by our group together with CD4zeta. This combination vector was able to suppress
      HIV-1 infection without impairing HIV-1-dependent effector activities of CD4zeta.
      In addition, the number of CD4zeta-modified CD8(+) T cells maintained similar
      levels to that of the control even under HIV-1 infection. These results suggest
      that protecting CD4zeta-modified CD8(+) T cells from HIV-1 infection is required
      for prolonged HIV-1-specific immune surveillance.

PMID- 25998392
TI  - 4-Hydroxynonenal induces persistent insolubilization of TDP-43 and alters its
      intracellular localization.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
      by progressive degeneration of motor neurons. TDP-43 has been found to be a major
      component of ubiquitin-positive inclusions in ALS. Aberrant TDP-43, which is
      found in inclusions, is phosphorylated and is re-distributed from the nucleus to
      the cytoplasm. Alterations of TDP-43 protein, particularly
      insolubilization/aggregation and cytosolic distribution are thought to be
      involved in the pathogenesis of ALS. Levels of 4-hydroxynonenal (HNE), a marker
      of oxidative stress, have been reported to be elevated in sporadic ALS patients.
      However, the effects of HNE on TDP-43 are unclear. In this study, we found that
      HNE treatment of cells causes insolubilization, phosphorylation, and partial
      cytosolic localization of TDP-43. HNE-induced cytosolic TDP-43 was diffusely
      localized and only a small proportion of TDP-43 localized to stress granules,
      which are transient structures. HNE-induced TDP-43 insolubilization and
      phosphorylation were even observed 24 h after washout of HNE. We also showed that
      the cysteine residues of TDP-43 are responsible for HNE-induced insolubilization
      of TDP-43. Our results indicate that HNE can cause biochemical changes of TDP-43,
      which resemble the aberrant alterations of this protein in ALS, and suggest that
      upregulation of HNE could be a risk factor for ALS. 

PMID- 25998393
TI  - MafB antagonizes phenotypic alteration induced by GM-CSF in microglia.
AB  - Microglia are tissue-resident macrophages which are distributed throughout the
      central nervous system (CNS). Recent studies suggest that microglia are a unique
      myeloid population distinct from peripheral macrophages in terms of origin and
      gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM
      CSF), a pleiotropic cytokine regulating myeloid development, has been shown to
      stimulate proliferation and alter phenotype of microglia in vitro. However, how
      its signaling is modulated in microglia is poorly characterized. MafB, a bZip
      transcriptional factor, is highly expressed in monocyte-macrophage lineage cells
      including microglia, although its role in microglia is largely unknown. We
      investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary
      microglia. We found that Mafb-deficient microglia grew more rapidly than wild
      type microglia in response to GM-CSF. Moreover, the expression of genes
      associated with microglial differentiation was more downregulated in Mafb
      deficient microglia cultured with GM-CSF. Notably, such differences between the
      genotypes were not observed in the presence of M-CSF. In addition, we found that
      Mafb-deficient microglia cultured with GM-CSF barely extended their membrane
      protrusions, probably due to abnormal activation of RhoA, a key regulator of
      cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative
      regulator of GM-CSF signaling in microglia. These findings could provide new
      insight into the modulation of cytokine signaling by transcription factors in
      microglia. 

PMID- 25998394
TI  - Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP
      inhibitor.
AB  - Among synthetic kinesin spindle protein (KSP) inhibitor compounds, KPYB10602, a
      six-member lactam-fused carbazole derivative was the most potent in vitro against
      cell growth of human ovarian cancer, A2780. KPYB10602 caused dose-dependent
      suppression of tumor growth in vivo. Mitotic arrest due to KPYB10602 was
      confirmed in vitro, and was characterized by inhibition of securin degradation.
      Apoptosis after mitotic arrest was associated with an increase in the ratio of
      pro-apoptotic Bax to anti-apoptotic Bcl-2. Increase of reactive oxygen species
      (ROS) and caspase pathway were also involved. Furthermore, KPYB10602 caused
      little neurotoxicity in vivo. Therefore, KPYB10602 could be a promising candidate
      as an anti-tumor agent with reduced adverse events for treating human ovarian
      cancer.

PMID- 25998395
TI  - Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses
      in early HIV-1 infection.
AB  - HLA class II-restricted CD4(+) T lymphocytes play an important role in
      controlling HIV-1 replication, especially in the acute/early infection stage.
      But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up
      regulating the invariant chain associated with immature HLA-II (Ii). Although
      functional heterogeneity of various Nef activities, including down-regulation of
      HLA class I (HLA-I), is well documented, our understanding of Nef-mediated
      evasion of HLA-II-restricted immune responses during acute/early infection
      remains limited. Here, we examined the ability of Nef clones from 47 subjects
      with acute/early progressive infection and 46 subjects with chronic progressive
      infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface
      of HIV-infected cells. HLA-I down-regulation function was preserved among
      acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation
      functions displayed relatively broad dynamic ranges. Nef's ability to down
      regulate HLA-DR and up-regulate Ii correlated positively at this stage,
      suggesting they are functionally linked in vivo. Acute/early Nef clones also
      exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions
      compared to chronic Nef clones. Taken together, our results support enhanced Nef
      mediated HLA class II immune evasion activities in acute/early compared to
      chronic infection, highlighting the potential importance of these functions
      following transmission.

PMID- 25998396
TI  - Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under
      extreme nutrient deprivation conditions.
AB  - Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating
      type of cancer with high mortality. Given the dense stroma and poor
      vascularization, accessibility to nutrients is limited in the tumor
      microenvironment. Here, we aimed to elucidate the role of autophagy in promoting
      the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived
      media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity
      and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial
      depolarization. NDM also time-dependently increased LC3-II accumulation, number
      of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These
      results suggested that autophagy was progressively activated through Akt- and
      AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors
      (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in
      NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z
      VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that
      autophagy is anti-apoptotic and sustains the survival of PANC-1 cells following
      extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic
      option for cancer cells located in the core of solid tumors with a nutrient
      deficient microenvironment. 

PMID- 25998397
TI  - Editorial Comment to Morphological effects of mitomycin C on urothelial responses
      to experimentally-induced urethral stricture in rats.

PMID- 25998398
TI  - Elotuzumab May Slow Multiple Myeloma.

PMID- 25998399
TI  - Dual Immunotherapies Shrink Melanomas.

PMID- 25998401
TI  - A Sleeping Beauty Screen Highlights Cancer Drivers in Osteosarcoma.
AB  - Osteosarcoma driver genes are enriched in the ERBB, PI3K-AKT-mTOR, MAPK, and axon
      guidance pathways. 

PMID- 25998402
TI  - Thiopurine Resistance in Childhood ALL Is Mediated by PRPS1 Mutations.
AB  - Mutations in the de novo purine biosynthesis enzyme PRPS1 drive thiopurine
      resistance in relapsed ALL. 

PMID- 25998403
TI  - MYC Regulates Expression of Pre-mRNA Splicing Machinery in Lymphoma.
AB  - MYC-mediated maintenance of proper mRNA splicing is essential for
      lymphomagenesis. 

PMID- 25998404
TI  - Telomere Dysfunction-Induced DNA Damage Drives Myelodysplastic Syndrome.
AB  - Telomere erosion-induced DNA damage alters myeloid progenitor differentiation and
      induces MDS. 

PMID- 25998405
TI  - Concurrent Gain of Oncogenes Drives Choroid Plexus Carcinoma.
AB  - TAF12, NFYC, and RAD54L are oncogenes required to initiate and maintain choroid
      plexus carcinoma (CPC). 

PMID- 25998407
TI  - The Effect of Moving Window on Acoustic Analysis.
AB  - OBJECTIVE: To investigate the effects of the moving window method on acoustic
      measures and discrimination ability between normal and disordered voices.
      METHODS: Fifty-three normal voices and 50 disordered voices were recruited. Three
      selection methods, the moving window method, the mid-vowel method, and the whole
      vowel method, were applied to each raw audio signal to determine the most stable
      segment of each signal. Acoustic parameters such as percent jitter, percent
      shimmer, signal-to-noise ratio (SNR), cepstral peak prominence (CPP), and
      correlation dimension (D2) were calculated. The Wilcoxon test was used to compare
      the stability of these segments across different methods. An artificial neural
      network was used for estimating how well disordered voices were discriminated
      from normal ones. RESULTS: Segments selected using the moving window method were
      more stable than those selected using the other two methods, meaning lower
      perturbation and nonlinear dynamic measurements as well as higher SNR and CPP
      values. The discrimination accuracy rate for the moving window method was 91.90
      +/- 8.73%, whereas the mid-vowel method and the whole vowel method were 72.34 +/-
      12.94% and 70.34 +/- 5.24%, respectively. CONCLUSION: The moving window method is
      capable of providing a more stable audio segment and can discriminate disordered
      voices from normal ones more effectively.

PMID- 25998408
TI  - Sex Differences in Pitch Range and Speech Fundamental Frequency After Arytenoid
      Adduction and Thyroplasty.
AB  - OBJECTIVE: The purpose of this study was to clarify the sex differences in pitch
      range (PR) and speech fundamental frequency (SFF) after arytenoid adduction (AA)
      combined with type 1 thyroplasty (TP1) in patients with unilateral vocal fold
      paralysis (UVFP) and to assess the cause of these differences. STUDY DESIGN: This
      is a retrospective review of clinical records. METHODS: The records of 50
      patients with UVFP for whom PR, SFF, and maximum phonation time (MPT) had been
      evaluated before and 1 year after AA combined with TP1 were analyzed. Patients
      consisted of 36 men and 14 women. In particular, in the 37 patients (24 men and
      13 women) who had >=2 semitones (STs) in preoperative PR (pre-PR), the
      differences and correlations between the pre-PR and the postoperative PR (post
      PR), SFF, and MPT were compared between the sexes. We also discussed cases of
      post-PR deterioration and abnormal SFF. RESULTS: The characteristics of PR in men
      are narrow pre-PR (14.7 +/- 11.5 STs) and significant extension of post-PR (22.6
      +/- 6.3 STs). MPT extended from 4.6 +/- 2.5 seconds to 14.8 +/- 7.2 seconds. In
      contrast, women had a wide pre-PR (18.1 +/- 7.2 STs) and showed no significant
      post-PR extension (21.7 +/- 7.8 STs). MPT extended from 5.1 +/- 1.9 seconds to
      16.8 +/- 7.2 seconds. Although there were no significant changes in average SFF,
      as well as the highest and lowest pitch after the operation, the variance of the
      pre-SFF tended to converge into the physiological range in the post-SFF (P =
      0.08). Compared with the SFF data of normal adult controls, post-SFF in the
      normal range was 46.0% (23/50). In patients who showed a >20% improvement in PR,
      normal post-SFF appeared in 68.8% of the patients (11/16). Particularly in those
      women, 83.3% (5/6) showed a normal post-SFF. Men showed greater difficulty in
      recovery of normal PR, SFF, and MPT; however, there were fewer patients (4.2%;
      1/24) with a PR deterioration of >20%. Regarding women, although some patients
      showed a parallel recovery in PR and SFF to the normal range, there was a high
      rate of patients showing PR deterioration (30.8%; 4/13). CONCLUSIONS: AA combined
      with TP1 resulted in the recovery of not only MPT but also PR and SFF. In
      addition, sex differences in operative effects were suggested. In men, although
      MPT is difficult to be fully recovered, PR deterioration was mild. In women,
      although MPT was more easily extended, PR deterioration occurred more readily
      because of operative effects such as hypermedialization of their smaller larynx.
      The post-PR variation appeared to be associated with SFF. Our results indicate
      the necessity to assess patients' PR and SFF even if their MPTs recover,
      particularly in patients with postoperative voice insufficiency.

PMID- 25998409
TI  - Hoarseness in School-Aged Children and Effectiveness of Voice Therapy in
      International Classification of Functioning Framework.
AB  - OBJECTIVES: The hoarseness in school-aged children disrupts the educational
      process because it affects the social progress, communication skills, and self
      esteem of children. Besides otorhinolaryngological examination, the first
      treatment option is voice therapy when hoarseness occurs. The aim of the study
      was to determine the factors increasing the hoarseness in school-aged children by
      parental interview and to know preferable voice therapy on school-aged children
      within the frame of International Classification of Functioning (ICF). STUDY
      DESIGN: Retrospective analysis of data gathered from patient files. METHOD: A
      total of 75 children (56 boys and 19 girls) were examined retrospectively. The
      age range of school-aged children is 7-14 years and average is 10.86 +/- 2.51. A
      detailed history was taken from parents of children involved in this study.
      Information about vocal habits of children was gathered within the frame of ICF
      and then the voice therapies of children were started by scheduling appointments
      by an experienced speech-language pathologist. RESULTS: The differences between
      before and after voice therapy according to applied voice therapy methods,
      statistically significant differences were determined between maximum phonation
      time values and s/z rate. The relationship between voice therapy sessions and s/z
      rate with middle degree significance was found with physiological voice therapy
      sessions. According to ICF labels, most of voice complaints are matching with
      "body functions" and "activity and limitations." CONCLUSIONS: The appropriate
      voice therapy methods for hoarseness in school-aged children must be chosen and
      applied by speech-language therapists. The detailed history, which is received
      from family during the examination, within the frame of ICF affects the processes
      of choosing the voice therapy method and application of them positively. Child's
      family is very important for a successful management.

PMID- 25998410
TI  - Fitzmaurice Voicework Pilot Study.
AB  - OBJECTIVES/DESIGN: A repeated-measures pilot study was used to investigate
      acoustic changes in the voices of participants in a Fitzmaurice Voicework (FV)
      teacher certification program. Maximum phonation time (MPT) was also measured.
      METHODS: Eleven participants with no reported voice problems were studied.
      Pretraining and posttraining recordings were made of each participant. Measures
      of MPT were made, and the recordings were analyzed for jitter, shimmer, and noise
      to-harmonics ratio (NHR). RESULTS: The measure of effect size for MPT was
      moderate, and there was an overall increase in MPT from pretraining to
      posttraining, with 70% of participants showing an increase in MPT. The measure of
      effect sizes for jitter, shimmer, and NHR were small, with measurements showing
      no significant changes from pretraining to posttraining. CONCLUSIONS: There were
      indications that FV training may have positive outcomes for actors and
      professional voice users, particularly in increasing MPT. Further studies with
      larger subject groups are needed to investigate the significance of the increase
      in MPT noted in this study and to test whether FV training can help to lower
      rates of shimmer and jitter.

PMID- 25998411
TI  - The Effect of Microphone Type on Acoustical Measures of Synthesized Vowels.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to compare microphones of
      different directionality, transducer type, and cost, with attention to their
      effects on acoustical measurements of period perturbation, amplitude
      perturbation, and noise using synthesized sustained vowel samples. STUDY DESIGN:
      This was a repeated measures design. METHOD: Synthesized sustained vowel stimuli
      (with known acoustic characteristics and systematic changes in jitter, shimmer,
      and noise-to-harmonics ratio) were recorded by a variety of dynamic and condenser
      microphones. Files were then analyzed for mean fundamental frequency (fo), fo
      standard deviation, absolute jitter, shimmer in dB, peak-to-peak amplitude
      variation, and noise-to-harmonics ratio. Acoustical measures following recording
      were compared with the synthesized, known acoustical measures before recording.
      RESULTS: Although informal analyses showed some differences among microphones,
      and analyses of variance showed that type of microphone is a significant
      predictor, t-tests revealed that none of the microphones generated different
      means compared with the generated acoustical measures. CONCLUSION: In this
      sample, microphone type, directionality, and cost did not have a significant
      effect on the validity of acoustic measures.

PMID- 25998412
TI  - MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative,
      mediates oxidative stress-induced apoptosis in AGS human gastric cancer cells.
AB  - MHY-449 is a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative
      designed and synthesized as a potential anticancer agent. The present study aimed
      to examine the anticancer activity and underlying mechanism of MHY-449. The cell
      viability assay performed in AGS human gastric carcinoma cells demonstrated that
      MHY-449 inhibited cell proliferation in a concentration-dependent manner. MHY-449
      induced AGS cell death via apoptosis. The underlying molecular mechanism of MHY
      449-mediated apoptosis was also investigated. MHY-449 promoted the upregulation
      of Fas and Fas-ligand, and activation of caspase-8, suggesting the involvement of
      a Fas-mediated extrinsic pathway in MHY-449-induced apoptosis. In addition, it
      was found that MHY-449-induced apoptosis was accompanied by the upregulation of
      Bax, p21(WAF1/CIP1), p27(KIP1), and p53 and suppression of Bcl-2. MHY-449
      exposure activated the caspase cascade and subsequent poly(ADP-ribose) polymerase
      (PARP) cleavage. Furthermore, the pan-caspase inhibitor, Z-VAD-FMK, significantly
      attenuated MHY-449-induced apoptosis, indicating that the apoptosis was caspase
      dependent. Moreover, the apoptogenic effect of MHY-449 was reactive oxygen
      species (ROS)-dependent. This result was confirmed by the induction of ROS by MHY
      449 and by evidence that the scavenging of ROS by N-acetyl-L-cysteine inhibited
      MHY-449-induced cell death. Taken together, these results demonstrated that MHY
      449 triggers apoptosis via caspase activation and ROS production. This result
      provides a novel mechanistic explanation and a basis for developing this compound
      as a novel candidate for human cancer therapy.

PMID- 25998413
TI  - Beta-amyloid plasma levels in adolescents with anorexia nervosa of the
      restrictive type.
AB  - BACKGROUND: Reduced plasma leptin and elevated homocysteine (Hcy) are known to
      lead to increased beta-amyloid (Abeta) production, besides being hallmarks of
      anorexia nervosa (AN) of the restrictive type. AN subjects display several
      neuropsychiatric manifestations, which may entail Abeta-mediated altered synaptic
      functions. The aim of this study consisted in assessing Abeta plasma levels in AN
      patients. METHODS: A total of 24 adolescent female AN outpatients were recruited
      together with 12 age-comparable healthy controls. For each subject we assessed
      Abeta40 and leptin plasma levels, as well as APOE genotype. Hcy plasma levels
      were also determined in AN patients who underwent clinical characterization,
      including the Eating Disorder Inventory-3 (EDI-3), the Children's Depression
      Inventory (CDI) and the estimation of the speed of BMI loss (DPI, disease
      progression index). RESULTS: Plasma Abeta40 levels were similar between patients
      and controls, while a marked reduction was observed for leptin (~80%) in AN
      patients. Abeta40 plasma levels failed to correlate with leptin, while a linear
      correlation was present with Hcy (r = 0.50, p < 0.03). Examined clinical features
      were not related with Abeta40 plasma levels, with the only exception of the DPI
      (r = 0.47, p < 0.03). CONCLUSION: This exploratory study does not support a
      significant role for altered Abeta production in AN-associated dysfunctions.
      Further studies are required to clarify whether exceptions to this conclusion can
      be drawn for those patients expressing significantly elevated Hcy plasma levels
      or for those progressing more rapidly.

PMID- 25998414
TI  - Genetic manipulation of RPS5 gene expression modulates the initiation of
      commitment of MEL cells to erythroid maturation: Implications in understanding
      ribosomopathies.
AB  - Impairment of ribosome biogenesis contributes to the molecular pathophysiology of
      ribosomopathies by deregulating cell-lineage specific proliferation,
      differentiation and apoptosis decisions of haematopoietic progenitor cells. Here,
      using pro-erythroblast-like murine erythroleukemia (MEL) cells, a model system of
      erythroid maturation, we aimed to investigate whether genetic manipulation of
      RPS5 expression affects the capacity of cells to grow and differentiate in
      culture. Parental MEL cells stably transfected with full length RPS5 cDNA in
      sense (MEL-C14 culture) or antisense (MEL-antisenseRPS5 culture) orientation, as
      well as MEL cells transiently transfected with siRNAs specific for RPS5 gene
      silencing (MEL-RPS5siRNA culture) were assessed for their ability to fully
      execute their erythroid maturation program in culture. The data obtained thus far
      indicate that: a) MEL-antisenseRPS5 exhibit a pronounced delay in the initiation
      of differentiation, as well as an impairment of commitment, since the continuous
      presence of the inducer in culture is required for the cells to fully execute
      their erythroid maturation program. b) RNAi-mediating silencing of RPS5 gene
      expression resulted in the inability of MEL cells to differentiate; however, when
      these cells were allowed to recapitulate normal RPS5 gene expression levels they
      regained their differentiation capacity by accumulating high proportion of
      erythroid mature cells. c) Interestingly the latter, is accompanied by
      morphological changes of cells and an impairment of their proliferation and
      apoptosis potential. Such data for the first time correlate the RPS5 gene
      expression levels with the differentiation capacity of MEL cells in vitro, a fact
      that might also have implications in understanding ribosomopathies.

PMID- 25998415
TI  - Generalized-stacking-fault energy and twin-boundary energy of hexagonal close
      packed Au: A first-principles calculation.
AB  - Although solid Au is usually most stable as a face-centered cubic (fcc)
      structure, pure hexagonal close-packed (hcp) Au has been successfully fabricated
      recently. However, the phase stability and mechanical property of this new
      material are unclear, which may restrict its further applications. Here we
      present the evidence that hcp -> fcc phase transformation can proceed easily in
      Au by first-principles calculations. The extremely low generalized-stacking-fault
      (GSF) energy in the basal slip system implies a great tendency to form basal
      stacking faults, which opens the door to phase transformation from hcp to fcc.
      Moreover, the Au lattice extends slightly within the superficial layers due to
      the self-assembly of alkanethiolate species on hcp Au (0001) surface, which may
      also contribute to the hcp -> fcc phase transformation. Compared with hcp Mg, the
      GSF energies for non-basal slip systems and the twin-boundary (TB) energies for
      and twins are larger in hcp Au, which indicates the more difficulty in generating
      non-basal stacking faults and twins. The findings provide new insights for
      understanding the nature of the hcp -> fcc phase transformation and guide the
      experiments of fabricating and developing materials with new structures.

PMID- 25998417
TI  - RNAi-mediated knockdown of inhibin alpha subunit increased apoptosis in granulosa
      cells and decreased fertility in mice.
AB  - Inhibin alpha (INHalpha), a member of TGFbeta superfamily, is an important
      modulator of reproductive function that plays a vital role in follicular changes,
      cell differentiation, oocyte development, and ultimately in mammalian
      reproduction. However, the role of inhibin alpha in female fertility and ovarian
      function remains largely unknown. To define its role in reproduction, transgenic
      mice of RNAi-INHalpha that knock down the INHalpha expression by shRNAi were
      used. Inhibin alpha subunit gene was knocked down successfully at both
      transcriptional and translational levels by RNAi PiggyBac transposon (Pbi)
      mediated recombinant pshRNA vectors and purified DNA fragments were microinjected
      into mouse zygotes. Results showed that transgenic female mice were sub-fertile
      and exhibited 35.28% reduction in litter size in F1 generation relative to wild
      type. The decreased litter size associated with the reduction in the number of
      oocytes ovulated after puberty. Serum INHalpha level was significantly decreased
      in both 3 and 6 weeks; whereas, FSH was significantly increased in 3 weeks but
      not in 6 weeks. Furthermore, suppression of INHalpha expression significantly
      promoted apoptosis by up-regulating Caspase-3, bcl2, INHbetaB and GDF9 and down
      regulated Kitl and TGFbetaRIII genes both at transcriptional and translational
      levels. Moreover, it also dramatically reduced the progression of G1 phase of
      cell cycle and the number of cells in S phase as determined by flow cytometer.
      These results indicate that suppression of INHalpha expression in RNAi-transgenic
      mice leads to disruption of normal ovarian regulatory mechanism and causes
      reproductive deficiencies by promoting cellular apoptosis, arresting cellular
      progression and altering hormonal signaling. 

PMID- 25998418
TI  - ATG12-ATG3 connects basal autophagy and late endosome function.
AB  - In addition to supporting cell survival in response to starvation or stress,
      autophagy promotes basal protein and organelle turnover. Compared to our
      understanding of stress-induced autophagy, little is known about how basal
      autophagy is regulated and how its activity is coordinated with other cellular
      processes. We recently identified a novel interaction between the ATG12-ATG3
      conjugate and the ESCRT-associated protein PDCD6IP/Alix that promotes basal
      autophagy and endolysosomal trafficking. Moreover, ATG12-ATG3 is required for
      diverse PDCD6IP-mediated functions including late endosome distribution, exosome
      secretion, and viral budding. Our results highlight the importance of late
      endosomes for basal autophagic flux and reveal distinct roles for the core
      autophagy proteins ATG12 and ATG3 in controlling late endosome function. 

PMID- 25998419
TI  - Role of HER-2 activity in the regulation of malignant meningioma cell
      proliferation and motility.
AB  - Meningiomas are common types of intracranial tumor. Invasive and malignant
      meningiomas present a significant therapeutic challenge due to high rates of
      recurrence and invasion. Understanding the molecular mechanism of invasion may
      assist in designing novel therapeutic approaches and improving patient survival
      rates. The HER-2 gene has been demonstrated to be a useful predictor of tumor
      aggression, which promotes the survival and growth of cancer cells through the
      mitogen-activated protein kinase and/or phosphatidylinositol 3-kinase (PI3K)/AKT
      pathway. Until now, few studies have investigated the associateion between
      meningiomas and the expression of HER-2, and the significance of HER-2 in
      meningiomas remains to be elucidated. The present study aimed to investigate the
      effects of the HER-2 gene on the biological behaviors of human malignant
      meningioma cells. The results demonstrated that downregulation of the expression
      of HER-2 by small interfering RNA in human meningioma cells significantly
      inhibited cell motility and proliferation, led to cell cycle arrest at the G0/G1
      phase and increased early apoptosis. By contrast, the overexpression of HER-2
      group resulted in meningioma cell invasion, migration and proliferation being
      significantly enhanced, cell cycle was promoted at the G1/S-phase and early
      apoptosis was decreased. Accordingly, the inhibition of HER-2 also prevented the
      protein expression of PI3K and phosphorylated AKT. The results demonstrated that
      regulation of the HER-2 gene can affect the proliferation, apoptosis, invasion
      and metastasis abilities of human meningioma cells in vitro. Furthermore,
      PI3K/AKT may contribute to the carcinogenesis and development of human
      meningiomas in combination with HER-2.

PMID- 25998416
TI  - From bench to bedside: What do we know about hormone receptor-positive and human
      epidermal growth factor receptor 2-positive breast cancer?
AB  - Breast cancer is a heterogeneous disease. Thanks to extensive efforts from
      research scientists and clinicians, treatment for breast cancer has advanced into
      the era of targeted medicine. With the use of several well-established
      biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and
      progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2),
      breast cancer patients can be categorized into multiple subgroups with specific
      targeted treatment strategies. Although therapeutic strategies for HR-positive
      (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive
      (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an
      overlooked subgroup without tailored therapeutic options. In this review, we have
      summarized the molecular characteristics, etiology, preclinical tools and
      therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention
      of both the research and the medical community on HR+ HER2+ breast cancer, and to
      advance patient care for this subtype of disease. 

PMID- 25998420
TI  - A Ten-Year Longitudinal Study of Caries among Patients Aged 14-72 Years in
      Norway.
AB  - There are few longitudinal studies in which the development of caries over a long
      period of time has been studied for different age groups. Such studies are
      important because they can provide information to assess future needs for dental
      care and the implications if the development of caries is different for patients
      in different age groups. We describe changes in caries during the period 2003
      2012 for several birth cohorts in Norway, using longitudinal data collected
      annually for each individual during a period of 10 years. The data set included
      patients born during the period 1940-1989 who received regular dental care in the
      public dental services in the county of Hedmark - altogether 7,519 patients.
      Information about caries was obtained from the electronic patient records. Nearly
      90% of the patients had no caries for at least 5 years during the 10-year study
      period, and nearly 50% had no caries for at least 8 years. This pattern was
      similar for all birth cohorts. The mean number of carious teeth per patient
      decreased from 2003 to 2012. This decrease was particularly large at the end of
      the period and among the oldest birth cohorts, i.e. those born in the periods
      1940-1949 and 1950-1959. Our findings indicate that the need for restorative
      treatment is reducing, particularly in the older age groups. Fewer dentists and
      more dental hygienists may be needed in the future to provide routine follow-up
      and care.

PMID- 25998421
TI  - Effects of dietary nitrate supplementation on the oxygen cost of exercise and
      walking performance in individuals with type 2 diabetes: a randomized, double
      blind, placebo-controlled crossover trial.
AB  - Dietary nitrate supplementation has been shown to reduce the oxygen (O2) cost of
      exercise and enhance exercise tolerance in healthy individuals. This study
      assessed whether similar effects could be observed in individuals with type 2
      diabetes (T2DM). In a randomized, double-blind, placebo-controlled crossover
      study, 48 participants with T2DM supplemented their diet for 4 days with either
      nitrate-rich beetroot juice (70ml/day, 6.43mmol nitrate/day) or nitrate-depleted
      beetroot juice as placebo (70ml/day, 0.07mmol nitrate/day). After each
      intervention period, resting plasma nitrate and nitrite concentrations were
      measured subsequent to participants completing moderate-paced walking. Pulmonary
      gas exchange was measured to assess the O2 cost of walking. After a rest period,
      participants performed the 6-min walk test (6MWT). Relative to placebo, beetroot
      juice resulted in a significant increase in plasma nitrate (placebo, 57+/-66 vs
      beetroot, 319+/-110uM; P < 0.001) and plasma nitrite concentration (placebo,
      680+/-256 vs beetroot, 1065+/-607nM; P < 0.001). There were no differences
      between placebo juice and beetroot juice for the O2 cost of walking (946+/-221 vs
      939+/-223ml/min, respectively; P = 0.59) and distance covered in the 6MWT (550+/
      83 vs 554+/-90m, respectively; P = 0.17). Nitrate supplementation did not affect
      the O2 cost of moderate-paced walking or improve performance in the 6MWT. These
      findings indicate that dietary nitrate supplementation does not modulate the
      response to exercise in individuals with T2DM. 

PMID- 25998422
TI  - Plasma F2-isoprostane class VI isomers at 12-18 weeks of pregnancy are associated
      with later occurrence of preeclampsia.
AB  - Preeclampsia (PE) has long been associated with early oxidative stress, although
      the symptoms occur later in pregnancy. We have hypothesized that the oxidative
      stress in PE, as characterized by the presence of F2-isoprostane (F2-isoP)
      isomers in late pregnancy, should already be present in plasma at the first
      regular visit of the obstetrical follow-up. There are 64 possible isomers of F2
      isoPs derived from the oxidation of arachidonic acid (AA), but only one of these
      isomers has been investigated so far in PE, the classical 8-iso-PGF2alpha. Here,
      we have investigated two regioisomers of class III (8-iso-15(R)-PGF2alpha and 8
      iso-PGF2alpha) and a mix of two isomers of class VI ((+/-)5-iPF2alpha-VI) in
      plasma samples collected prospectively at 12-18 weeks from normotensive controls
      (n = 60) and pregnant mothers who developed PE later in pregnancy (n = 33). The
      plasma samples were subjected to alkaline hydrolysis followed by liquid-liquid
      extraction to extract total F2-isoPs for later quantification by HPLC-MS/MS. The
      F2-isoPs were normalized to either plasma volume or polyunsaturated fatty acid
      (PUFA) levels measured by GC-FID in plasma phospholipids. Early in pregnancy,
      only the class VI F2-isoP isomers were found at concentrations significantly
      higher in women developing PE later in pregnancy (+13%; p = 0.0074).
      Normalization of F2-isoPs to their substrate, AA, or the omega-3 to omega-6 ratio
      improved the predictability of PE as determined by receiver operating
      characteristic (from area under the curve of 0.67 to 0.68 and 0.70 respectively).
      Interestingly, omega-3 fatty acids were 25% higher in the control group than in
      the PE group (P = 0.0225). Omega-6 PUFAs correlated with F2-Isop isomers only in
      cases of PE (r > 0.377; P >0.03, Spearman correlation). In sum, this study
      indicates that specific isomers of class VI are significant predictors of PE.
      This work also suggests that F2-isoP isomers are not all generated and eliminated
      to the same extent and are influenced by the PUFA composition of plasma
      phospholipids. 

PMID- 25998423
TI  - Nox4-dependent activation of cofilin mediates VSMC reorientation in response to
      cyclic stretching.
AB  - Vascular smooth muscle cells (VSMCs) are subjected to various types of mechanical
      forces within the vessel wall. Although it is known that VSMCs undergo cell body
      reorientation in response to mechanical stimulation, how this mechanical stretch
      is transduced within the cell into biochemical signals causing cytoskeleton
      reorganization remains unclear. Cofilin, a protein that controls actin dynamics,
      is activated by Slingshot phosphatase-dependent serine 3 dephosphorylation by
      redox-dependent mechanisms. Nox4 is a main source of reactive oxygen species
      (ROS) in the vessel wall that localizes in association with the cytoskeleton.
      Therefore, we hypothesize that Nox4 mediates redox-dependent activation of
      cofilin, which is required for cytoskeletal reorganization and cell reorientation
      after mechanical stimulation. In this study, we found that mechanical stretch
      stimulates ROS production in VSMCs and that the signaling that leads to cell
      reorientation requires hydrogen peroxide but not superoxide. Indeed, mechanical
      stretch induces cofilin activation and stretch-induced cytoskeletal
      reorganization, and cell reorientation is inhibited in cells where cofilin
      activity has been downregulated. Importantly, Nox4-deficient cells fail to
      activate cofilin and to undergo cell reorientation, a phenotype rescued by the
      expression of a constitutively active cofilin mutant. Our results demonstrate
      that in VSMCs mechanical stimulation activates cofilin by a Nox4-dependent
      mechanism and that this pathway is required for cytoskeleton reorganization and
      cell reorientation. 

PMID- 25998425
TI  - Ethanol in Olive Fruit. Changes during Ripening.
AB  - Ethanol is one of the precursors of ethyl esters, the virgin olive oil quality
      parameter for the "extra" category recently adopted by the European Union and
      International Olive Oil Council. Although ethyl ester content has great
      importance for virgin olive oil classification, the origin of ethanol is not
      clear. A possible source of ethanol may be the olive fruit itself while it
      remains on the tree. Variation of fruit ethanol content during ripening was
      studied for three different olive cultivars: 'Picual', 'Hojiblanca', and
      'Arbequina'. Ethanol was measured in fruit homogenates by HS-SPME-GC-FID. The
      ethanol content varied between 0.56 and 58 mg/kg. 'Hojiblanca' fruits showed the
      highest ethanol concentration. For all of the cultivars, ethanol content of fruit
      increased during the ripening process, although a clear cultivar-dependent effect
      was observed because 'Hojiblanca' fruits showed the most significant raise.
      Therefore, results indicated that ethanol can be accumulated during fruit
      maturation on the olive tree. 

PMID- 25998424
TI  - Resveratrol and N-acetylcysteine influence redox balance in equine articular
      chondrocytes under acidic and very low oxygen conditions.
AB  - Mature articular cartilage is an avascular tissue characterized by a low oxygen
      environment. In joint disease, acidosis and further reductions in oxygen levels
      occur, compromising cartilage integrity.This study investigated how acidosis and
      very low oxygen levels affect components of the cellular redox system in equine
      articular chondrocytesand whether the antioxidants resveratrol and N
      acetylcysteine could modulate this system. We used articular chondrocytes
      isolated from nondiseased equine joints and cultured them in a 3-D alginate bead
      system for 48h in <1, 2, 5, and 21% O2 at pH 7.2 or 6.2 in the absence or
      presence of the proinflammatory cytokine, interleukin-1beta (10ng/ml).In
      addition, chondrocytes were cultured with resveratrol (10uM) or N-acetylcysteine
      (NAC) (2mM).Cell viability, glycosaminoglycan (GAG) release, mitochondrial
      membrane potential (DeltaPsim), reactive oxygen species (ROS), GSH:GSSG ratio,
      and SOD1 and SOD2 protein expression were measured. Very low levels of oxygen
      (<1%), acidosis (pH 6.2), and exposure to IL-1beta led to reductions in cell
      viability, increased GAG release, alterations in DeltaPsim and ROS levels, and
      reduced GSH:GSSG ratio. In addition, SOD1 and SOD2 protein expressions were
      reduced. Both resveratrol and NAC partially restored DeltaPsim and ROS levels and
      prevented GAG release and cell loss and normalized SOD1 and SOD2 protein
      expression. In particular NAC was highly effective at restoring the GSH:GSSG
      ratio.These results show that the antioxidants resveratrol and N-acetylcysteine
      can counteract the redox imbalance in articular chondrocytes induced by low
      oxygen and acidic conditions. 

PMID- 25998426
TI  - True cutaneous chondroma: a case report.

PMID- 25998428
TI  - [The application of CRISPR-Cas9 gene editing technology in viral infection
      diseases].
AB  - The RNA-guided Cas9 nuclease from microbial clustered regularly interspaced short
      palindromic repeats (CRISPR) adaptive immune system has been used to facilitate
      efficient genome engineering in eukaryotic cells. The specific targeted genome is
      recognized and cut by gRNA-directed CRISPR/Cas9 complex, specifically by the
      endonuclease Cas9. The targeted gene locus could be repaired either by homology
      directed repair or nonhomologous end joining, thus achieving a desired editing
      outcome. Viruses infect cells through specific receptors, and then the viral
      genome is transcribed, replicated and translated to complete its life cycle. As a
      result, some DNA virus and retrovirus genomes are integrated into the cellular
      genome. Gene therapy is a new trend to treat viral infected diseases. Given its
      designable sequence-specific editing of the targeted genome, CRISPR/Cas9 has
      tremendous potential in treating persistent and latent viral infections. In this
      review, we summarize the mechanism and progresses of CRISPR/Cas9, and also
      highlight its therapeutic application in infectious diseases.

PMID- 25998429
TI  - [Identification and characterization of HIV-1 transmitted /founder viruses].
AB  - During the spread of human immunodeficiency virus type 1 (HIV-1) in the mucosa,
      the entire genetic diversity of the viruses is significantly reduced. The vast
      majority of HIV-1 mucosal infections are established by one or a few viruses and
      ultimately develop into systemic infections, thus the initial virus is called
      transmitted/founder virus (T/F virus). The study of T/F virus will benefit
      understanding its key characteristics resulting in successful viral replication
      in the new host body, which may provide novel strategies for the development of
      AIDS vaccines, pre-exposure prophylaxis and other therapeutic interventions. In
      this review, we summarize the discovery and evolutionary characteristics of T/F
      virus as well as early immune response after HIV-1 infection, which will
      establish the basis to explore the features of T/F viruses.

PMID- 25998430
TI  - Molecular epidemiology and evolution of human enterovirus 71 and hand, foot and
      mouth disease.
AB  - Human enterovirus 71(EV71), one of the major pathogens of the hand, foot and
      mouth disease (HFMD), causes skin rashes in palms, feet and mouth ulcers and
      complication in the central nervous system such as aseptic meningitis and acute
      flaccid paralysis that may lead to death. EV71 infection has been reported to be
      associated with many outbreaks of HFMD worldwide, especially the great outbreaks
      that occurred in the Asia-Pacific region and caused numerous death since 1997.
      The studies of molecular epidemiology and evolution of EV71 are important for the
      prevention and control of HFMD since no vaccines and antiviral drugs have been
      developed except symptomatic treatment for HFMD. In this review, we summarize
      genotype classification, temporal and spatial distribution, evolutionary
      characteristics and modes of EV71 as well as typical EV71 epidemics. Further
      studies on EV71 and HFMD may lead to better understanding of pathological
      mechanisms of EV71, development of antiviral drugs and prevention and control of
      HFMD.

PMID- 25998431
TI  - Adaptation strategies: how environmental fungi become fatal?
AB  - Most fungi contributing to systemic human infections are environmental pathogens,
      whose fatal pathogenicity is largely derived from their survival strategies
      developed to adapt to a plethora of natural stressors. A well-studied example of
      such pathogens is Cryptococcus neoformans. C. neoformans can cause life
      threatening cryptococcosis and meningoencephalitis, which claim more than 600 000
      lives annually. Recent findings reveal that the coordinated application of
      strategies like morphotype transition, cell-cell communication and cellular
      heterogeneity play critical roles in optimizing fungal survival both inside and
      outside of the host. The understanding of biological blueprint of these
      adaptation behaviors will thus help characterize Cryptococcus factors that shape
      its interaction with the human host, and further contribute to the research of
      other environmental fungal pathogens.

PMID- 25998432
TI  - Application of the SCCmec element in the molecular typing of methicillin
      resistant Staphylococcus aureus.
AB  - Acquisition of the staphylococcal chromosome cassette mec (SCCmec) is one of the
      key reasons for the resistance of methicillin-resistant Staphylococcus aureus
      (MRSA). SCCmec is composed of a mec gene complex encoding the PBP2a determinant
      that is responsible for the beta-lactam resistance of MRSA, and a ccr gene
      complex encoding recombinases that mediate the integration of SCCmec into and its
      excision from the recipient chromosome, and so-called three junkyard (J) regions
      of different sizes. The SCCmec elements carried by MRSA from different geographic
      locations are diverse, and each type contains characteristic DNA fragments in
      size. These characteristics of SCCmec element may facilitate the usage of SCCmec
      in the molecular typing of MRSA strains. In this review, we summarize the
      structure and function of SCCmec elecments, and discuss the application of SCCmec
      elements in the molecular typing of MRSA.

PMID- 25998433
TI  - Genetic characteristics of vancomycin resistance gene cluster in Enterococcus
      spp.
AB  - Vancomycin resistant enterococci has become an important nosocomial pathogen
      since it is discovered in late 1980s. The products, encoded by vancomycin
      resistant gene cluster in enterococci, catalyze the synthesis of peptidoglycan
      precursors with low affinity with glycopeptide antibiotics including vancomycin
      and teicoplanin and lead to resistance. These vancomycin resistant gene clusters
      are classified into nine types according to their gene sequences and
      organization, or D-Ala:D-Lac (VanA, VanB, VanD and VanM) and D-Ala:D-Ser (VanC,
      VanE, VanG, VanL and VanN) ligase gene clusters based on the differences of their
      encoded ligases. Moreover, these gene clusters are characterized by their
      different resistance levels and infection models. In this review, we summarize
      the classification, gene organization and infection model of vancomycin resistant
      gene cluster in Enterococcus spp.

PMID- 25998434
TI  - Update on antimicrobial resistance in Clostridium difficile.
AB  - Clostridium difficile is the leading cause of healthcare-associated diarrhea.
      Since 2002, the morbidity and mortality rates of C. difficile infection have
      increased dramatically in Europe and North America. The emergence of C. difficile
      strains that are resistant to multiple antimicrobial agents can complicate
      prevention programs and potential treatment. Although most clinical isolates are
      still susceptible to metronidazole and vancomycin, heteroresistance to
      metronidazole and increasing vancomycin MICs (minimum inhibitory concentrations)
      have been reported. The prevalence of resistance to other antimicrobial agents,
      including erythromycin and moxifloxacin, is highly variable in different
      countries and regions. The exact mechanism of reduced susceptibility to
      metronidazole or vancomycin is still not clear. The principal mechanism of
      erythromycin, fluoroquinolones and rifamycins resistance in C. difficile is
      determined by target alterations. This review will focus primarily on the
      antimicrobial susceptibility patterns and resistance mechanisms of C. difficile
      in order to provide an up-to-date review on the topic.

PMID- 25998435
TI  - Distinct quasispecies characteristics and positive selection within the core gene
      in chronic hepatitis B virus infected child and adult patients.
AB  - There are significant differences in clinical characteristics between chronic
      hepatitis B virus infected (CHB) child and adult patients. Viral quasispecies
      characteristics are associated with its pathogenic properties. For hepatitis B
      virus (HBV), its core region is the main immune recognition region for its
      enriched epitopes. In our study, we discuss the quasispecies characteristics and
      positive selection within core gene within chronic HBV infected child and adult
      patients. By analyzing 170 core gene sequences from child CHB patients and 121
      core genes sequences from adult CHB patients, quasispecies characteristics were
      described by sequence complexity, diversity, non-synonymous substitution ratio
      (dN) and synonymous substitution ratios (dS). In addition, positive selection
      sites were also determined by bioinformatics tools. Then, all these parameters
      were compared between child and adult CHB patient groups. Compared with child
      patients, adult patients with CHB showed distinct quasispecies characteristics
      within the core region, had a higher sequence complexity and diversity and more
      positive selection sites, suggesting that the adult CHB patients had a higher
      immune selection pressure on the HBV core gene. Reduced selection pressure on the
      HBV core gene in hepatitis B e antigen (HBeAg)-positive CHB patients than HBeAg
      negative CHB patients were observed in both adult and child patient groups. The
      majority of the screened positive selection sites lay within human leukocyte
      antigens (HLA)-restricted epitopes. In conclusion, this study analyzed the
      quasispecies characteristics discrepancy between child and adult patients with
      CHB, and revealed the possible reason for the distinct clinical characteristics
      in the perspective of population genetics.

PMID- 25998436
TI  - Preparation and immunogenicity-evaluation of typhoid O-specific polysaccharides
      bio-conjugate vaccines.
AB  - Typhoid fever caused by Salmonella Typhi is still a major public health problem
      in developing countries. In this study, we constructed a genetically modified
      Salmonella Typhi strain expressing O-specific polysaccharides (OPS) antigen
      conjugated to a carrier, recombinant Pseudomonas aeruginosa exotoxin A(rEPA N29).
      The conjugates (OPS-rEPA N29) were further purified and evaluated for their
      immunogenicity. The results of ELISA showed that the conjugates evoked higher
      titers of IgG than OPS, suggesting that rEPAN29 increased immunogenicity of OPS
      significantly as a carrier. Moreover, three injections with 3-week interval
      evoked slightly higher titers of IgG than three injections with 2-week interval.
      However, injection of excess conjugates could not evoke higher titers of IgG
      against lipid polysaccharide (LPS). In summary, our study provides a new strategy
      for preparing polysaccharides-protein conjugate vaccines as well as similar bio
      conjugate vaccines of other Gram-negative pathogens.

PMID- 25998437
TI  - Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce
      cell cycle G2arrest and cell apoptosis.
AB  - In the event of acute infection, only a few HIV-1 viral variants can establish
      the initial productive clinical infection, and these viral variants are known as
      transmitted/founder viruses (T/F viruses). As one of the accessory proteins of
      HIV-1, viral protein R (Vpr) plays an important role in viral replication.
      Therefore, the characterization of T/F virus Vpr is beneficial to understand how
      virus replicates in a new host. In this study, flow cytometry was used to analyze
      the effect of G2arrest and cell apoptosis induced by the T/F virus Vpr and the
      chronic strain MJ4 Vpr. The results showed that the ability of T/F virus ZM246
      Vpr and ZM247 Vpr inducing G2arrest and cell apoptosis are more potent than the
      MJ4 Vpr. The comparison of protein sequences indicated that the amino acids of
      77, 85 and 94 contain high freqency mutations, suggesting that these sites may be
      involved in inducing G2arrest and cell apoptosis. Taken together, our work
      suggests that in acute infections, T/F viruses increase the capacity of G2arrest
      and cell apoptosis and promote viral replication and transmission in a new host
      by Vpr genetic mutation.

PMID- 25998438
TI  - The effect of quorum sensing system for growth competitiveness on Shigella
      flexneri.
AB  - Quorum sensing (QS) regulates the onset of bacterial social responses related to
      cell density. Comparison between the gene sequences of all components of QS
      system of Escherichia coli and Shigella strains, shows that the QS system is
      generally lost or mutated in Shigella. Since AI-2 is produced and processed by
      the lsr operon, we analyzed the potential function of the lsr operon. We first
      detected AI-2 in Shigella flexneri 2a strain 301 through the reporter bacteria
      Vibrio harveyi BB170, indicating that S. flexneri can produce AI-2. Then, the lsr
      operon of E. coli MG1655 was cloned into S. flexneri using the Golden Gate
      method. Colony counting experiments showed that the QS system recovery strain had
      growth advantage over the wild-type strain when they were mixed and cultured. The
      preliminary comparative proteomics analysis showed that the lsr operon could be
      expressed and the abundance of stress response proteins also changed when the QS
      system was introduced into S. flexneri.

PMID- 25998439
TI  - The function of PlcR in Bacillus anthracis vaccine strain A16R.
AB  - Bacillus anthracis, B. thuringiensis and B. cereus are members of the B. cereus
      group. They share high genetic similarity. Whereas plcR (Phospholipase C
      regulator) usually encodes a functional pleiotropic activator protein in B.
      cereus and B. thuringiensis isolates, a characteristic nonsense mutation is found
      in all B. anthracis strains investigated, making the gene dysfunctional. To study
      the function of PlcR in B. anthracis, we used the B. cereus CMCC63301 genome as a
      template and constructed a recombinant expression plasmid pBE2A-plcR, and
      introduced it into the B. anthracis vaccine strain A16R, and then analyzed the
      activity of the hemolysin and sphingomyelinase. The results showed that
      transformation of B. anthracis with plasmid pBE2A-plcR carrying the native B.
      cereus plcR gene active the expression of sphingomyelinase gene, but did not
      activate expression of hemolysin genes of B. anthracis A16R.

PMID- 25998441
TI  - Thickness of the bony otic capsule: etiopathogenetic perspectives on superior
      canal dehiscence syndrome.
AB  - The etiology of superior canal dehiscence (SCD) is controversial. An
      embryological perspective suggests that SCD may occur through the failure of
      postnatal bone formation over the superior semicircular canal (SC), whereas an
      acquired theory suggests that trauma or pressure from the overlying temporal lobe
      could break or gradually thin the SC. We infer the etiology of SCD by comparing
      the thickness of the bony otic capsule of the unaffected side of SCD patients
      with that of non-SCD participants. Twelve SCD patients (13 SCD ears and 11 normal
      ears) and 34 age-matched controls (68 ears) were included. The control group was
      subdivided into an aerated group (49 ears) and a nonaerated group (19 ears), as
      defined by the presence of air cells above the SC. A high-resolution temporal
      bone CT was performed in all participants. The thicknesses of the SC, horizontal
      canal (HC) and posterior canal (PC) of the unaffected ears of SCD patients were
      compared with those of the controls. The SC of the unaffected side in the SCD
      group (n = 11, 0.41 +/- 0.23 mm) was significantly thinner than the one in the
      control group (n = 68, 0.64 +/- 0.21 mm, p = 0.002). The HC and PC were also
      thinner in the SCD group (n = 24, 0.58 +/- 0.11 and 1.39 +/- 0.31 mm,
      respectively) than in the controls (0.70 +/- 0.08 and 1.61 +/- 0.32 mm; p <
      0.0001 and p = 0.005, respectively). The SC, HC and PC thicknesses were also
      compared between the aerated and nonaerated ears within the control group. The SC
      was significantly thicker in the aerated group (0.73 +/- 0.14 mm) than in the
      nonaerated group (0.60 +/- 0.23 mm; p = 0.046); however, no significant
      difference was observed for the HC and PC thickness (aerated group, n = 49, 0.72
      +/- 0.07 and 1.67 +/- 0.34 mm; nonaerated group, n = 19, 0.70 +/- 0.09 and 1.59
      +/- 0.34 mm; p = 0.350 and p = 0.428, respectively). The bony otic capsule was
      significantly thinner in the SCD patients than in the controls. However, even
      within unaffected individuals, SCs lacking overlying air cells were also thinner
      than those with overlying air cells. These results suggest that both
      embryological and acquired factors affect the occurrence of SCD.

PMID- 25998442
TI  - PI3K/mTORC2 regulates TGF-beta/Activin signalling by modulating Smad2/3 activity
      via linker phosphorylation.
AB  - Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming
      growth factor-beta signalling pathways play an important role in regulating many
      cellular functions. However, the molecular mechanisms underpinning this crosstalk
      remain unclear. Here, we report that PI3K signalling antagonizes the Activin
      induced definitive endoderm (DE) differentiation of human embryonic stem cells by
      attenuating the duration of Smad2/3 activation via the mechanistic target of
      rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation
      of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity.
      This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3
      ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of
      PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3
      activity, promoting a more robust mesendoderm and endoderm differentiation. These
      findings present a new and direct crosstalk mechanism between these two pathways
      in which mTORC2 functions as a novel and critical mediator. 

PMID- 25998443
TI  - Effect of Ambroxol and Beclomethasone on Lipopolysaccharide-Induced Nitrosative
      Stress in Bronchial Epithelial Cells.
AB  - BACKGROUND: Nitrosative stress is involved in different airway diseases.
      Lipopolysaccharide (LPS) induces neutrophil-related cytokine release and
      nitrosative stress in human bronchial epithelial (BEAS-2B) cells alone or with
      human polymorphonuclear neutrophils (PMNs). Ambroxol protects against oxidative
      stress, and beclomethasone dipropionate is an anti-inflammatory drug. OBJECTIVES:
      We evaluated the ability of ambroxol and/or beclomethasone dipropionate to
      inhibit LPS-induced expression/release of RANTES, IL-8, inducible NO synthase
      (iNOS), myeloperoxidase (MPO) and 3-nitrotyrosine (3-NT: nitrosative stress
      biomarker) in BEAS-2B +/- PMNs stimulated with LPS (1 MUg/ml). METHODS: The
      effect of ambroxol and/or beclomethasone dipropionate on IL-8, RANTES and iNOS
      levels was assessed by Western blot analysis; IL-8, MPO and 3-NT levels were
      measured by ELISA. Cell viability was assessed by the trypan blue exclusion test.
      RESULTS: In BEAS-2B alone, LPS (at 12 h) increased RANTES/iNOS expression and IL
      8 levels (p < 0.001). Ambroxol suppressed LPS-induced RANTES expression and IL-8
      release (p < 0.001), whilst inhibiting iNOS expression (p < 0.05). Beclomethasone
      dipropionate had no effect on RANTES but halved iNOS expression and IL-8 release.
      Coculture of BEAS-2B with PMNs stimulated IL-8, MPO and 3-NT production (p <
      0.001), potentiated by LPS (p < 0.001). Ambroxol and beclomethasone dipropionate
      inhibited LPS-stimulated IL-8, MPO and 3-NT release (p < 0.05).
      Ambroxol/beclomethasone dipropionate combination potentiated the inhibition of IL
      8 and 3-NT production in BEAS-2B with PMNs (p < 0.05 and p < 0.01, respectively).
      Ambroxol and/or beclomethasone dipropionate inhibited nitrosative stress and the
      release of neutrophilic inflammatory products in vitro. CONCLUSION: The additive
      effect of ambroxol and beclomethasone dipropionate on IL-8 and 3-NT inhibition
      suggests new therapeutic options in the treatment of neutrophil-related
      respiratory diseases such as chronic obstructive pulmonary disease and
      respiratory infections.

PMID- 25998444
TI  - Comparison of in-hospital mortality in patients with COPD, asthma and asthma-COPD
      overlap exacerbations.
AB  - BACKGROUND AND OBJECTIVE: Obstructive airway diseases, such as asthma and chronic
      obstructive pulmonary disease (COPD), have airflow limitation associated with
      chronic inflammation. Using a national inpatient database in Japan, we aimed to
      evaluate factors affecting in-hospital mortality in patients with asthma, COPD or
      asthma-COPD overlap (ACO). METHODS: We retrospectively collected data for
      inpatients (age >40 years) with exacerbation of COPD and/or asthma in 1073
      hospitals across Japan between July 2010 and May 2013. We performed multivariable
      logistic regression analysis to examine the association of various factors with
      all-cause in-hospital mortality, including diagnosis of ACO, asthma alone and
      COPD alone. RESULTS: Of 30 405 eligible patients, in-hospital mortality in
      patients with ACO, asthma alone and COPD alone was 2.3%, 1.2% and 9.7%,
      respectively. COPD patients had a significantly higher mortality than ACO
      patients (odds ratio 1.96; 95% confidence interval: 1.38-2.79); patients with
      asthma alone showed lower mortality (0.70; 0.50-0.97). Higher mortality was also
      significantly associated with older age, male gender, lower body mass index, more
      severe dyspnoea, lower level of consciousness, worse activities of daily life and
      higher daily dose of corticosteroids. CONCLUSION: Asthma alone was associated
      with lower mortality, but COPD alone was associated with higher mortality than
      ACO.

PMID- 25998445
TI  - Ratio of Acceleration Time to Ejection Time for Assessing Aortic Stenosis
      Severity.
AB  - BACKGROUND: Inconsistencies in the grading of aortic valve stenosis are frequent
      (24-38%). Guidelines highlight the waveform shape when discrepancies are present.
      Our aim was to evaluate the severity of aortic stenosis by the ratio of
      acceleration time to ejection time (AT/ET). METHODS: Between January 2011 and
      January 2013, patients with at least moderate aortic stenosis (valve area < 1.5
      cm(2) ) evaluated in our echocardiography laboratory were enrolled. Clinical data
      were recorded including symptoms attributable to aortic stenosis. Quantitative
      echocardiographic Doppler parameters as ejection dynamics (ejection time and
      acceleration time) and conventional parameters, and usual laboratory test
      including natriuretic peptides (NT-proBNP) were analyzed. RESULTS: One hundred
      eight patients with aortic valve stenosis were recruited (mean age 77 +/- 7
      years; 57% women). Comorbidity of the patients was frequent: 85% hypertension,
      59% diabetes, 31% chronic renal failure, 26% smokers, mean body mass index 30.0
      +/- 6.6 kg/m(2) . Ninety-six patients (90%) were symptomatic at the index visit.
      Using a cutoff of 0.35, AT/ET had a sensitivity of 77% and a specificity of 100%
      to discriminate symptomatic patients. Serum value of NT-proBNP was higher in
      patients with AT/ET > 0.35 (9885 +/- 3111 vs. 2600 +/- 1175, P < 0.001). This
      ratio showed a good correlation with indexed left ventricle mass (r = 0.60, P <
      0.001), DVI (r = -0.56, P < 0.001), and AVA (r = -0.49, P < 0.001). CONCLUSIONS:
      Ejection dynamics through aortic valve, particularly AT/ET ratio, is a useful
      tool for assessing aortic stenosis severity, with a good correlation with flow
      independent parameters in aortic stenosis.

PMID- 25998446
TI  - Use of mobile apps: a patient-centered approach.
AB  - OBJECTIVES: This study explored what smartphone health applications (apps) are
      used by patients, how they learn about health apps, and how information about
      health apps is shared. METHODS: Patients seeking care in an academic ED were
      surveyed about the following regarding their health apps: use, knowledge,
      sharing, and desired app features. Demographics and health information were
      characterized by summary statistics. RESULTS: Of 300 participants, 212 (71%)
      owned smartphones, 201 (95%) had apps, and 94 (44%) had health apps. The most
      frequently downloaded health apps categories were exercise 46 (49%), brain
      teasers 30 (32%), and diet 23 (24%). The frequency of use of apps varied as six
      (6%) of health apps were downloaded but never used, 37 (39%) apps were used only
      a few times, and 40 (43%) health apps were used once per month. Only five apps
      (2%) were suggested to participants by health care providers, and many
      participants used health apps intermittently (55% of apps <= once a month).
      Participants indicated sharing information from 64 (59%) health apps, mostly
      within social networks (27 apps, 29%) and less often with health care providers
      (16 apps, 17%). CONCLUSIONS: While mobile health has experienced tremendous
      growth over the past few years, use of health apps among our sample was low. The
      most commonly used apps were those that had broad functionality, while the most
      frequently used health apps encompassed the topics of exercise, diet, and brain
      teasers. While participants most often shared information about health apps
      within their social networks, information was less frequently shared with
      providers, and physician recommendation played a small role in influencing
      patient use of health apps.

PMID- 25998447
TI  - Model-Based Deep Brain Stimulation Programming for Parkinson's Disease: The GUIDE
      Pilot Study.
AB  - BACKGROUND: Achieving optimal results following deep brain stimulation (DBS)
      typically involves several months of programming sessions. The Graphical User
      Interface for DBS Evaluation (GUIDE) study explored whether a visual programming
      system could help clinicians accurately predetermine ideal stimulation settings
      in DBS patients with Parkinson's disease. METHODS: A multicenter prospective,
      observational study was designed that utilized a blinded Unified Parkinson's
      Disease Rating Scale (UPDRS)-III examination to prospectively assess whether DBS
      settings derived using a neuroanatomically based computer model (Model) could
      provide comparable efficacy to those determined through traditional, monopolar
      review-based programming (Clinical). We retrospectively compared the
      neuroanatomical regions of stimulation, power consumption and time spent on
      programming using both methods. RESULTS: The average improvement in UPDRS-III
      scores was 10.4 +/- 7.8 for the Model settings and 11.7 +/- 8.7 for the Clinical
      settings. The difference between the mean UPDRS-III scores with the Model versus
      the Clinical settings was 0.26 and not statistically significant (p = 0.9866).
      Power consumption for the Model settings was 48.7 +/- 22 MUW versus 76.1 +/- 46.5
      MUW for the Clinical settings. The mean time spent programming using the Model
      approach was 31 +/- 16 s versus 41.4 +/- 29.1 min using the Clinical approach.
      CONCLUSION: The Model-based DBS settings provided similar benefit to the Clinical
      settings based on UPDRS-III scores and were often arrived at in less time and
      required less power than the Clinical settings.

PMID- 25998448
TI  - Percentage of patients with spondyloarthritis in patients referred because of
      chronic back pain and performance of classification criteria: experience from the
      Spondyloarthritis Caught Early (SPACE) cohort.

PMID- 25998449
TI  - Use and perceived relevance of health-related Internet sites and online contact
      with peers among young people with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate the frequency of use and relevance of health-related
      Internet (HRI) sites and online peer support groups and their association with
      demographic, disease-related and psychosocial variables in young people with JIA.
      METHODS: In a cross-sectional study, 176 young people (10-27 years of age) with
      JIA were asked to complete a questionnaire. The frequency of using HRI sites
      (regarding information, medication use and aspects of JIA relating to social
      life), online peer contact and perceived relevance of HRI sites and online peer
      communication were determined. Associations with demographic variables, disease
      activity, medication, emotional behaviour and coping were also examined. RESULTS:
      Seventy-one per cent of the 142 respondents had used the Internet to search for
      general information on JIA, but specific topics, such as medication, were
      searched for less often. Twenty-five per cent of respondents had visited a forum
      or had contacted peers online. The perceived relevance of HRI sites and online
      peer contact was rated low (median 2.0 and 1.0, respectively; scale 0-10). Apart
      from female gender (P < 0.01), none of the demographic and disease-related
      factors were associated with HRI site use. Coping styles, confrontation and
      reassuring thoughts were associated with increased HRI site use, but only in
      males. Internalizing and externalizing problem behaviour were not significantly
      associated. CONCLUSION: The frequency of HRI site use among young people with JIA
      was less than expected and was considered of low relevance. HRI sites in their
      present form cannot replace traditional information as an additional source to
      increase knowledge.

PMID- 25998450
TI  - Intravenous neridronate in the treatment of acute painful knee osteoarthritis: a
      randomized controlled study.
AB  - OBJECTIVE: The aim of this randomized, double-blind, placebo-controlled study was
      to assess the efficacy of i.v. neridronate in controlling pain in patients with
      acute painful knee OA. METHODS: Sixty-four patients with acute knee pain (<3
      months duration) suffering from knee OA with an MRI showing bone marrow lesions
      (BMLs) were randomized to receive either neridronate 100 mg given four times over
      10 days or placebo. After 50 days the patients underwent clinical assessment and
      a further MRI was performed. Primary outcome was pain changes measured by a
      visual analogue scale (VAS; range 0-100). Secondary endpoints were WOMAC pain
      score, McGill pain questionnaire and 36-Item Short Form Health Survey. BMLs were
      evaluated by whole-organ MRI score. RESULTS: At the day of the last infusion the
      VAS decreased significantly more in the neridronate group [from 59.0 (s.d. 14.7)
      to 30.4 (s.d. 15.6); -48.4%; P < 0.001]. Fifty days later the VAS remained
      unchanged in the placebo group, while a further significant decrease was observed
      in the neridronate group [from 30.4 (s.d. 15.6) to 9.4 (s.d. 10.8); -69.1%; P <
      0.001]. Significant improvements compared with the placebo group were found for
      most of the other indices of pain and quality of life. The BMLs score in the
      neridronate group showed significant decreases compared with basal values and
      those of the placebo-treated patients. Four months after the treatment, 72% of
      the placebo-treated patients resumed analgesic or anti-inflammatory drugs, but
      only 12.9% resumed treatment in the neridronate group. CONCLUSION: In patients
      with acute painful knee OA, four infusions of neridronate are associated with a
      clinically relevant pain benefit. TRIAL REGISTRATION: ClinicalTrials.gov
      (http://clinicaltrials.gov), NCT01803360.

PMID- 25998451
TI  - Calcium-containing crystals enhance receptor activator of nuclear factor kappaB
      ligand/macrophage colony-stimulating factor-mediated osteoclastogenesis via
      extracellular-signal-regulated kinase and p38 pathways.
AB  - OBJECTIVE: Diseases associated with calcium-containing crystal deposition can
      lead to local bone erosion. We aimed to determine whether calcium-containing
      crystal-hydroxyapatite, beta-tricalcium phosphate and CPPD enhanced
      osteoclastogenesis and to define underlying mechanisms of action. METHODS:
      Osteoclastogenesis was studied by culturing murine RAW 264.7 osteoclast precursor
      cells with RANK ligand (RANKL)/ M-CSF and/or calcium-containing crystals, and
      observing the tartrate-resistant acid phosphatase (TRAP)-positive multinucleated
      cells and TRAP activity. Resorption pit formation was used to evaluate osteoclast
      activity. Real-time RT-PCR analysis revealed osteoclast marker genes, including
      TRAP, cathepsin K and calcitonin receptor (CTR). Western blotting was used to
      analyse the phosphorylation levels of signal transduction molecules. RESULTS:
      Three kinds of calcium-containing crystal significantly enhanced RANKL/M-CSF
      induced osteoclastogenesis in RAW 264.7 cells, as evidenced by the increased
      number of TRAP-positive multinucleated cells, TRAP activity and resorption pit
      formation in a dose-dependent manner. Hydroxyapatite, beta-tricalcium phosphate
      and CPPD treatments significantly enhanced RANKL/M-CSF-induced mRNA expression of
      TRAP, cathepsin K and CTR. Moreover, the three kinds of calcium-containing
      crystal enhanced the phosphorylation of extracellular-signal-regulated kinase and
      p38 in RANKL/M-CSF-treated cells. CONCLUSION: We concluded that calcium
      containing crystals can promote osteoclastogenesis and bone resorption through
      the extracellular-signal-regulated kinase and p38 pathways. Together with
      synovial activation, this mechanism may be important in the pathogenesis of
      destructive arthropathies triggered by calcium-containing crystals.

PMID- 25998452
TI  - Three-month isolated digital gangrene as an initial manifestation of classic
      polyarteritis nodosa.

PMID- 25998453
TI  - Aminobenzohydrazide based colorimetric and 'turn-on' fluorescence chemosensor for
      selective recognition of fluoride.
AB  - Chemosensors based on aminobenzohydrazide Schiff bases bearing pyrene/anthracene
      as fluorophores have been designed and synthesized for F(-) ion recognition. The
      addition of fluoride ions to the receptors causes a dramatically observable
      colour change from pale yellow to brown/red. (1)H NMR studies confirm that the F(
      ) ion facilitates its recognition by forming hydrogen bond with hydrogens of
      amide and amine groups. Moreover these sensors have also been successfully
      applied to detection of fluoride ion in commercial tooth paste solution. 

PMID- 25998454
TI  - Review on synthesis of ferrocene-based redox polymers and derivatives and their
      application in glucose sensing.
AB  - The interest in glucose biosensors persisted over many years and persistent
      efforts have been made to develop long term stable glucose biosensors with
      precision, smart analytical performance, good linearity and resistance to
      communal interferences. In this regard, ferrocene-based polymers and derivatives
      (FBPDs) for the development of glucose biosensor (GBs) as redox mediators have
      acquired utmost attention of the scientists, especially in the second generation
      biosensors, as a large number of innovative molecules have been synthesized. Most
      of the FBPDs are considered as active components in the development of GBs, due
      to their ease of modification, biocompatibility, stability, large surface area,
      good electrical conductivity and especially excellent redox properties. This
      review provides a brief description of synthesis, analytical performance and
      glucose sensing application of ferrocene-based dendrimers, polythiophenes,
      polypyrroles, polyethylenimine, chitosan and carbon nano tubes (CNTs). Moreover,
      the analytical performance of ferrocene-based glucose biosensors (FBGBs) is
      summarized and the problems associated with the construction of GBs and the
      future trends are discussed. 

PMID- 25998455
TI  - Direct determination of the nutrient profile in plant materials by femtosecond
      laser-induced breakdown spectroscopy.
AB  - Femtosecond laser-induced breakdown spectroscopy (fs-LIBS) has been used for the
      first time for quantitative determination of nutrients in plant materials from
      different crops. A highly heterogeneous population of 31 samples, previously
      analyzed by inductively coupled plasma optical emission spectroscopy, covering a
      wide range of matrices was interrogated. To tackle the analysis, laser-induced
      plasmas under argon atmosphere of pellets prepared from sieved cryogenically
      ground leaves were studied. Predictive functions based on univariate and
      multivariate modeling of optical emissions associated to macro- (Ca, Mg, and P)
      and micronutrients (Cu, Fe, Mn and Zn) were designed. Hierarchical cluster
      analysis was performed to select representative calibration (n(cal)=17) and
      validation (n(val)=14) datasets. The predictive performance of calibration
      functions over fs-LIBS data was compared with that attained on spectral
      information from nanosecond LIBS (ns-LIBS) operating at different wavelengths
      (1064 nm, 532 nm, and 266 nm). Findings established higher accuracy and less
      uncertainty on mass fractions quantification from fs-LIBS, whatever the modeling
      approach. Quality coefficients below 20% for the accuracy error on mass
      fractions' prediction in unknown samples, and residual predictive deviations in
      general above 5, were obtained. In contrast, only multivariate modeling
      satisfactorily handled the non-linear variations of emissions in ns-LIBS, leading
      to 2-fold decrease in the root mean square error of prediction (RMSEP) of Ca, Mg,
      P, Cu, Fe, Mn and Zn in comparison with the univariate approach. But still, an
      averaged quality coefficient about 35% and residual predictive deviations below 3
      were found. Similar predictive capabilities were observed when changing the laser
      wavelength. Although predicted values by ns-LIBS multivariate modeling exhibit
      better agreement with reference mass fractions as compared to univariate
      functions, fs-LIBS conducts better quantification of nutrients in plant materials
      since it is less dependent on the chemical composition of the matrices.

PMID- 25998456
TI  - Variable ranking based on the estimated degree of separation for two
      distributions of data by the length of the receiver operating characteristic
      curve.
AB  - Variable responses are fundamental for all experiments, and they can consist of
      information-rich, redundant, and low signal intensities. A dataset can consist of
      a collection of variable responses over multiple classes or groups. Usually some
      of the variables are removed in a dataset that contain very little information.
      Sometimes all the variables are used in the data analysis phase. It is common
      practice to discriminate between two distributions of data; however, there is no
      formal algorithm to arrive at a degree of separation (DS) between two
      distributions of data. The DS is defined herein as the average of the sum of the
      areas from the probability density functions (PDFs) of A and B that contain
      a>=percentage of A and/or B. Thus, DS90 is the average of the sum of the PDF
      areas of A and B that contain >=90% of A and/or B. To arrive at a DS value, two
      synthesized PDFs or very large experimental datasets are required. Experimentally
      it is common practice to generate relatively small datasets. Therefore, the
      challenge was to find a statistical parameter that can be used on small datasets
      to estimate and highly correlate with the DS90 parameter. Established statistical
      methods include the overlap area of the two data distribution profiles, Welch's t
      test, Kolmogorov-Smirnov (K-S) test, Mann-Whitney-Wilcoxon test, and the area
      under the receiver operating characteristics (ROC) curve (AUC). The area between
      the ROC curve and diagonal (ACD) and the length of the ROC curve (LROC) are
      introduced. The established, ACD, and LROC methods were correlated to the DS90
      when applied on many pairs of synthesized PDFs. The LROC method provided the best
      linear correlation with, and estimation of, the DS90. The estimated DS90 from the
      LROC (DS90-LROC) is applied to a database, as an example, of three Italian wines
      consisting of thirteen variable responses for variable ranking consideration. An
      important highlight of the DS90-LROC method is utilizing the LROC curve
      methodology to test all variables one-at-a-time with all pairs of classes in a
      dataset. 

PMID- 25998457
TI  - An all-solid-state polymeric membrane Pb2+-selective electrode with bimodal pore
      C60 as solid contact.
AB  - An all-solid-state polymeric membrane Pb(2+) ion-selective electrode (Pb(2+)-ISE)
      based on bimodal pore C60 (BP-C60) as solid contact has been developed. A BP-C60
      film can be readily formed on the surface of a glassy carbon electrode by
      electrochemical deposition. Cyclic voltammetry and electrochemical impedance
      spectroscopy have been employed to characterize the BP-C60 film. The large double
      layer capacitance and fast charge-transfer capability make BP-C60 favorable to be
      used as solid contact for developing all-solid-state ISEs. The all-solid-state BP
      C60-based Pb(2+)-ISE shows a Nernstian response in the range from 1.0*10(-9) to
      1.0*10(-3)M with a detection limit of 5.0*10(-10)M. The membrane electrode not
      only displays an excellent potential stability with the absence of a water layer
      between the ion-selective membrane and the underlying BP-C60 solid contact, but
      also is insensitive to interferences from O2, CO2 and light. The proposed solid
      contact Pb(2+)-ISE has been applied to determine Pb(2+) in real water samples and
      the results agree well with those obtained by anodic stripping voltammetry. 

PMID- 25998458
TI  - Growth of cedar-like Au nanoparticles coating on an etched stainless steel wire
      and its application for selective solid-phase microextraction.
AB  - A novel cedar-like Au nanoparticles (AuNPs) coating was fabricated on an etched
      stainless steel (SS) wire by direct chemical deposition and used as an efficient
      and unbreakable solid phase microextraction (SPME) fiber. The etched SS wire
      offers a rough surface structure for subsequent growth of AuNPs in chloroauric
      acid solution. As a result, the uniform cedar-like AuNPs coating with larger
      surface area was tightly attached to the etched SS wire substrate. The AuNPs
      coated etched SS fiber (AuNPs/SS) was examined for SPME of ultraviolet (UV)
      filters, phthalate esters and aromatic hydrocarbons coupled to high-performance
      liquid chromatography with UV detection. The fabricated fiber exclusively
      exhibited excellent extraction efficiency and selectivity for some aromatic
      hydrocarbons. Influential parameters of extraction and desorption time,
      temperature, stirring rate and ionic strength were investigated and optimized.
      The limits of detection ranged from 0.008 MUg L(-1) to 0.037 MUg L(-1). The
      single fiber repeatability varied from 3.90% to 4.50% and the fiber-to-fiber
      reproducibility ranged from 5.15% to 6.87%. The recovery of aromatic hydrocarbons
      in real water samples spiked at 2.0 MUg L(-1) and 20 MUg L(-1) ranged from 94.38%
      to 106.2% with the relative standard deviations below 6.44%. Furthermore the
      growth of the cedar-like AuNPs coating can be performed in a highly reproducible
      manner. This fabricated fiber exhibits good stability and withstands at least 200
      extraction and desorption replicates.

PMID- 25998459
TI  - NMR-aided differentiation of enantiomers: Signal enantioresolution.
AB  - NMR-aided enantiodiscrimination using chiral auxiliaries (CAs) is a recognized
      method for differentiating enantiomers and for measuring enantiomeric ratios
      (er). Up to the present, the study, optimization, and comparison of such methods
      have been performed based on the enantiodifferentiation of NMR signals via
      analyzing non-equivalent chemical-shift values (DeltaDeltadelta) of the
      diastereoisomeric species formed. However, a poor and non-reliable comparison of
      results is often obtained via the analysis of DeltaDeltadelta exclusively. In
      here, the concept of enantioresolution of an individual NMR signal and its
      importance for NMR-aided enantiodifferentiation studies is introduced and
      discussed. In addition, the enantioresolution quotient, E, is proposed as the
      parameter to describe its quantification. Complementary to measuring
      DeltaDeltadelta, the experimental determination of E allows a more reliable
      interpretation of the results and opens up new possibilities for the study of
      enantiodifferentiation data derived from novel NMR experiments, setup
      improvements or new CAs. Finally, the different relationships between signal
      enantiodifferentiation, signal enantioresolution, and other main experimental
      issues of enantiodifferentiation experiments are addressed. 

PMID- 25998460
TI  - Dual gold nanoparticle lateflow immunoassay for sensitive detection of
      Escherichia coli O157:H7.
AB  - Two patterns of signal amplification lateral flow immunoassay (LFIA), which used
      anti-mouse secondary antibody-linked gold nanoparticle (AuNP) for dual AuNP-LFIA
      were developed. Escherichia coli O157:H7 was selected as the model analyte. In
      the signal amplification direct LFIA method, anti-mouse secondary antibody-linked
      AuNP (anti-mouse-Ab-AuNP) was mixed with sample solution in an ELISA well, after
      which it was added to LFIA, which already contained anti-E. coli O157:H7
      monoclonal antibody-AuNP (anti-E. coli O157:H7-mAb-AuNP) dispersed in the
      conjugate pad. Polyclonal antibody was the test line, and anti-mouse secondary
      antibody was the control line in nitrocellulose (NC) membrane. In the signal
      amplification indirect LFIA method, anti-mouse-Ab-AuNP was mixed with sample
      solution and anti-E. coli O157:H7-mAb-AuNP complex in ELISA well, creating a dual
      AuNP complex. This complex was added to LFIA, which had a polyclonal antibody as
      the test line and secondary antibody as the control line in NC membrane. The
      detection sensitivity of both LFIAs improved 100-fold and reached 1.14*10(3) CFU
      mL(-1). The 28 nm and 45 nm AuNPs were demonstrated to be the optimal dual AuNP
      pairs. Signal amplification LFIA was perfectly applied to the detection of milk
      samples with E. coli O157:H7 via naked eye observation.

PMID- 25998461
TI  - Developing a genetically encoded green fluorescent protein mutant for sensitive
      light-up fluorescent sensing and cellular imaging of Hg(II).
AB  - Hg(II) is well-known for quenching fluorescence in a distance dependent manner.
      Nevertheless, when we exposed the fluorophore of a green fluorescent protein
      (GFP) toward Hg(II), through H148C mutation, the GFP fluorescence could be
      "lighted up" by Hg(II) down to sub-nM level. The detection linear range is 0.5
      3.0 nM for protein solutions at 8.0 nM. The GFPH148C protein displayed a
      promising selectivity toward Hg(II) and also the cellular imaging capacity.
      Spectra measurements suggested that the ground-state redistribution of protein
      contributed to the fluorescence enhancement, which was found not limited to
      Hg(II), and thus presented an opening for building a pool of GFP-based
      chemosensors toward other heavy metal ions.

PMID- 25998462
TI  - A convenient and label-free fluorescence "turn off-on" nanosensor with high
      sensitivity and selectivity for acid phosphatase.
AB  - In this study, we reported a convenient label-free fluorescence nanosensor for
      rapid detection of acid phosphatase on the basis of aggregation-caused quenching
      (ACQ) and enzymolysis approach. The selectivity nanosensor was based on the
      fluorescence "turn off-on" mode, which possessed high sensitivity features. The
      original strong fluorescence intensity of CuInS2 QDs was quenched by sodium
      hexametaphosphate (NaPO3)6. The high efficiency of the quenching was caused by
      the non-covalent binding of positively charged CuInS2 QDs to the negatively
      charged (NaPO3)6 through electrostatic interactions, aggregating to form a CuInS2
      QDs/(NaPO3)6 complex. Adding acid phosphatase caused intense fluorescence of
      CuInS2 QDs/(NaPO3)6 to be recovered, and this was because of enzymolysis.
      (NaPO3)6 was hydrolyzed into small fragments and the high negative charge density
      decreased, which would weaken the strong electrostatic interactions. As a result,
      the quenched fluorescence "turned on". Under the optimum conditions, there was a
      good linear relationship between I/I0 (I and I0 were the fluorescence intensity
      of CuInS2 QDs/(NaPO3)6 system in the presence and absence of acid phosphatase,
      respectively) and acid phosphatase concentration in the range of 75-1500 nU mL(
      1) with the detection limit of 9.02 nU mL(-1). The proposed nanosensor had been
      utilized to detect and accurately quantify acid phosphatase in human serum
      samples with satisfactory results.

PMID- 25998463
TI  - Micellar electrokinetic chromatography of organic and peroxide-based explosives.
AB  - CE methods have been developed for the analysis of organic and peroxide-based
      explosives. These methods have been developed for deployment on portable, in
      field instrumentation for rapid screening. Both classes of compounds are neutral
      and were separated using micellar electrokinetic chromatography (MEKC). The
      effects of sample composition, separation temperature, and background electrolyte
      composition were investigated. The optimised separation conditions (25 mM sodium
      tetraborate, 75 mM sodium dodecyl sulfate at 25 degrees C, detection at 200 nm)
      were applied to the separation of 25 organic explosives in 17 min, with very high
      efficiency (typically greater than 300,000 plates m(-1)) and high sensitivity
      (LOD typically less than 0.5 mg L(-1); around 1-1.5 MUM). A MEKC method was also
      developed for peroxide-based explosives (10 mM sodium tetraborate, 100 mM sodium
      dodecyl sulfate at 25 degrees C, detection at 200 nm). UV detection provided LODs
      between 5.5 and 45.0 mg L(-1) (or 31.2-304 MUM), which is comparable to results
      achieved using liquid chromatography. Importantly, no sample pre-treatment or
      post-column reaction was necessary and the peroxide-based explosives were not
      decomposed to hydrogen peroxide. Both MEKC methods have been applied to pre-blast
      analysis and for the detection of post-blast residues recovered from controlled,
      small scale detonations of organic and peroxide-based explosive devices.

PMID- 25998464
TI  - Carnitine transporter CT2 (SLC22A16) is over-expressed in acute myeloid leukemia
      (AML) and target knockdown reduces growth and viability of AML cells.
AB  - AML (acute myeloid leukemia) cells have a unique reliance on mitochondrial
      metabolism and fatty acid oxidation (FAO). Thus, blocking FAO is a potential
      therapeutic strategy to target these malignant cells. In the current study, we
      assessed plasma membrane carnitine transporters as novel therapeutic targets for
      AML. We examined the expression of the known plasma membrane carnitine
      transporters, OCTN1, OCTN2, and CT2 in AML cell lines and primary AML samples and
      compared expression to normal hematopoietic cells. Of the three carnitine
      transporters, CT2 demonstrated the greatest differential expression between AML
      and normal cells. Using shRNA, we knocked down CT2 and demonstrated that target
      knockdown impaired the function of the transporter. In addition, knockdown of CT2
      reduced the growth and viability of AML cells with high expression of CT2 (OCI
      AML2 and HL60), but not low expression. CT2 knockdown reduced basal oxygen
      consumption without a concomitant increase in glycolysis. Thus, CT2 may be a
      novel target for a subset of AML. 

PMID- 25998465
TI  - Geometric perturbations in multiheaded papillary tip positions associated with
      acute ovine ischemic mitral regurgitation.
AB  - BACKGROUND: Novel surgical approaches are focusing on the "ventricular disease"
      of ischemic mitral regurgitation (IMR), to correct altered papillary muscle (PM)
      tip positions (apical displacement) and ameliorate leaflet tethering. Due to the
      anatomic complexity of the subvalvular apparatus, however, the precise geometric
      perturbations of the multiheaded PM tips associated with IMR remain
      uncharacterized. METHODS: In 6 adult sheep, we implanted 3 markers on each PM. To
      specifically identify distinct PM tips, 1 marker was placed on the PM origin of
      the dominant chord to the anterior, posterior, and commissural leaflets. Nine
      markers were placed on the edge of the posterior mitral leaflet, and 5 on the
      edge of the anterior mitral leaflet. Eight markers were sewn around the mitral
      annulus. Animals were studied immediately postoperatively, with biplane
      videofluoroscopy and transesophageal echocardiography, before and during acute
      snare occlusion of the proximal left circumflex coronary artery, to induce IMR.
      Papillary muscle tip and leaflet edge geometry was expressed as the orthogonal
      distance of each respective marker to the least-squares mitral annulus plane at
      end-systole. In addition, the distance from each PM tip marker to the mitral
      annulus "saddle horn" was calculated. RESULTS: Acute left circumflex occlusion
      significantly increased mitral regurgitation from a baseline of 0.7 +/- 0.3 to
      2.5 +/- 0.5 (P < .05). The IMR was associated with posterior leaflet restriction
      near the central leaflet edge, with simultaneous prolapse of both leaflets near
      the posterior commissure. No apical displacement of PM tips was observed during
      IMR, although the posterior PM moved farther away from the midseptal annulus.
      CONCLUSIONS: During acute ischemia, no apical displacement of any PM tip was
      observed. Posterior PM movement away from the annular saddle horn, and toward the
      annulus, was associated with IMR and leaflet prolapse near the posterior
      commissure, and with restriction near the valve center. These data may help guide
      development of surgical interventions aimed at PM repositioning.

PMID- 25998466
TI  - Microsurgical reconstruction of combined tracheal and total esophageal defects.
AB  - OBJECTIVE: Lesions involving both the trachea and the esophagus are often
      considered inoperable because of the lack of reliable reconstruction. The purpose
      of this study was to review our experience of combined supercharged jejunal and
      other flaps for tracheal and esophageal reconstruction. METHODS: A retrospective
      review of 5 consecutive cases with combined tracheal and total esophageal defects
      was performed. The esophageal defect was reconstructed with a supercharged
      jejunal flap, and the trachea was reconstructed with a free anterolateral thigh
      flap or a pedicled muscle flap. RESULTS: Primary diagnosis included tracheostoma
      recurrence after a total laryngectomy for laryngeal cancer in 2 patients and
      tracheoesophageal fistula due to esophageal stenting for complications from prior
      treatment for non-Hodgkin's lymphoma, parathyroid cancer, and esophageal cancer
      in 3 patients, respectively. Tracheal and esophageal reconstructions were staged
      in 4 patients, and 1 patient received simultaneous reconstruction. Tracheal
      necrosis developed in 1 patient with a mediastinal tracheostoma, and the patient
      eventually died of infection 2 months later. The other 4 patients recovered well
      and resumed an oral diet. CONCLUSIONS: Complex and often life-threatening lesions
      involving both the trachea and the esophagus are not necessarily inoperable. With
      careful planning, these combined defects can be safely reconstructed with
      multiple flaps with good functional outcomes and reasonable survival.

PMID- 25998467
TI  - Scoping the shape of an iceberg: the future of public involvement in heath
      policy: reflecting on 'Public involvement policies in health: exploring their
      conceptual basis'.

PMID- 25998468
TI  - A Potential Use of 3-D Scanning to Evaluate the Chemical Composition of Pork
      Meat.
AB  - The aim of this study was to determine the possibility of 3-D scanning method in
      chemical composition evaluation of pork meat. The sampling material comprised
      neck muscles (1000 g each) obtained from 20 pork carcasses. The volumetric
      estimation process of the elements was conducted on the basis of point cloud
      collected using 3-D scanner. Knowing the weight of neck muscles, their density
      was calculated which was subsequently correlated with the content of basic
      chemical components of the pork meat (water, protein and fat content, determined
      by standard methods). The significant correlations (P <= 0.05) between meat
      density and water (r = 0.5213), protein (r = 0.5887), and fat (r = -0.6601)
      content were obtained. Based on the obtained results it seems likely to employ
      the 3-D scanning method to compute the meat chemical composition. PRACTICAL
      APPLICATION: The use of the 3-D scanning method in industrial practice will allow
      to evaluate the chemical composition of meat in online mode on a dressing and
      fabrication line and in a rapid, noninvasive manner. The control of the raw
      material using the 3-D scanning will allow to make visual assessment more
      objective and will enable optimal standardization of meat batches prior to
      processing stage. It will ensure not only the repeatability of product quality
      characteristics, but also optimal use of raw material-lean and fat meat. The
      knowledge of chemical composition of meat is essential due to legal requirements
      associated with mandatory nutrition facts labels on food products.

PMID- 25998469
TI  - Analysis of insulin pump settings in children and adolescents with type 1
      diabetes mellitus.
AB  - AIM: To characterize current insulin pump settings used in young patients with
      type 1 diabetes mellitus (T1DM) and to assess their relationship to glycemic
      control. METHODS: This retrospective study included patients aged <18 yr old with
      T1DM >1 yr using a Medtronic pump device. Pump data including number of blood
      glucose (BG) tests per day, basal and bolus insulin parameters, carbohydrate
      ratio (CR), and insulin sensitivity factors (ISFs) were averaged over 14 d for
      statistical analyses. Anthropometric data and recent glycosylated hemoglobin A1c
      (HbA1c) were recorded. RESULTS: A total of 292 patients (144 males and 148
      females) were included in the study. Participants had a median age (interquartile
      range, IQR) of 12.9 yr (10.0-15.1 yr) and pump duration of 2.8 yr (1.5-4.2 yr).
      No significant differences in median HbA1c (IQR) were observed in preschool [n =
      14; HbA1c 7.8% (7.3-8.3%)], prepubertal [n = 105; HbA1c 8.1% (7.7-8.9%)], and
      adolescent subjects [n = 173; HbA1c 8.4% (7.7-9.0%)]. Adolescents took
      significantly fewer boluses and BG tests per day compared with younger children
      (p < 0.05). Age-specific diurnal variation in basal insulin delivery was noted.
      Additionally, stronger carbohydrate cover and weaker corrections were used in
      real-life compared with theoretical 500 and 100 rules, respectively. Lower HbA1c
      was associated with higher number of daily boluses, greater number of BG tests
      per day, lower average CR/500 rule ratio, and higher average ISF/100 rule ratio
      adjusted for age (R(2) = 0.22; p < 0.01). CONCLUSION: Insulin pump therapy
      requires continuous adjustments and glycemic targets are achieved by a minority.
      We believe this is the first study in pediatric cohort looking at association
      between CR and ISF with glycemic control.

PMID- 25998470
TI  - Mid-Calcaneal Length After Evans Calcaneal Osteotomy: A Retrospective Comparison
      of Wedge Locking Plates and Tricortical Allograft Wedges.
AB  - Evans calcaneal osteotomy remains a cornerstone in the correction of the flexible
      flatfoot. Although multiple techniques have been used to maintain the length of
      the lateral column, a low profile wedge locking plate was recently introduced as
      an alternative to the traditional tricortical allograft wedge. We hypothesized
      that the wedge locking plate would better maintain the mid-calcaneal length
      compared with the tricortical allograft wedge. To test this hypothesis, after
      Evans osteotomy, the mid-calcaneal length was measured in the immediate
      postoperative period and again at 3 and 6 months. A total of 24 patients met the
      inclusion criteria. The mean patient age was 48.1 years (range 11 to 66). Of the
      24 patients, 9 (37.5%) were treated with a tricortical allograft wedge and 15
      (62.5%) with a wedge locking plate. At 3 months postoperatively, the mean
      decrease in mid-calcaneal length was similar for the tricortical allograft wedge
      group (1.3 +/- 1.9 mm) and the wedge locking plate group (0.5 +/- 0.9 mm, p =
      .275). At 6 months postoperatively, however, the mean decrease in mid-calcaneal
      length was greater for the tricortical allograft wedge group (2.8 +/- 1.7 mm)
      than for the wedge locking plate group (0.6 +/- 0.7 mm, p = .004). The 2 groups
      demonstrated a similar incidence of dorsally displaced distal calcaneal fragments
      throughout the study endpoint (p >= .052). These results suggest that the wedge
      locking plate better maintains the mid-calcaneal length over time compared with
      the tricortical allograft wedge. 

PMID- 25998471
TI  - Mechanical Comparison of Headless Screw Fixation and Locking Plate Fixation for
      Talar Neck Fractures.
AB  - For talar neck fractures, open reduction and internal fixation have been thought
      to facilitate revascularization and prevent osteonecrosis. Newer screw systems
      allow for placement of cannulated headless screws, which provide compression by
      virtue of a variable pitch thread. The present study compared the biomechanical
      fixation strength of cannulated headless variable-pitch screw fixation and
      locking plate fixation. A reproducible talar neck fracture was created in 14
      fresh cadaver talar necks. Talar head fixation was then performed using 2
      cannulated headless variable-pitch 4-mm/5-mm diameter (4/5) screws (Acutrak;
      Acumed, Hillsboro, OR) and locking plate fixation. Headless variable-pitch screw
      fixation had lower failure displacement than did locking plate fixation. No
      statistically significant differences were found in failure stiffness, yield
      stiffness (p = .655), yield load (p = .142), or ultimate load between the 2
      fixation techniques. Cannulated headless variable-pitch screw fixation resulted
      in better failure displacement than locking plate fixation in a cadaveric talus
      model and could be considered a viable option for talus fracture fixation.
      Headless, fully threaded, variable-pitch screw fixation has inherent advantages
      compared with locking plate fixation, because it might cause less damage to the
      articular surface and can compress the fracture for improved reduction.
      Additionally, plate fixation can increase the risk of avascular necrosis owing to
      the wider incision and dissection of soft tissues. 

PMID- 25998472
TI  - Reverse Transfer of the Proximal Vascularized Fibula to Reconstruct the Lateral
      Malleolus: A Case Report and Literature Review.
AB  - Defects of the lateral malleolus and distal fibula occur occasionally, mainly
      because of severe trauma or wide resection of fibular neoplasms. These bony
      defects should be reconstructed to avoid persistent pain and to prevent an
      abnormal gait induced by ankle instability. Various methods of repair have been
      developed, including allografting, autologous iliac crest transplantation,
      scapular apophysis transplantation, and arthrodesis and prosthetic
      reconstruction. A reverse transfer of the proximal vascularized fibula is also
      effective. Its morphologic advantage is apparent, and the surgery is simple and
      direct, with no need for vascular anastomosis. We treated recurrent fibrous
      dysplasia in the distal fibula of a young male with wide resection and
      reconstruction using reverse transfer of the proximal, vascularized fibula. At
      the 6-year follow-up examination, the patient had an American Orthopaedic Foot
      and Ankle Society ankle-hindfoot score of 100, without any apparent
      complications. Additionally, we critically reviewed other methods for
      reconstructing the lateral malleolus and distal fibula and have concluded that
      reverse transfer of the proximal vascularized fibula compares favorably and could
      be the treatment of choice. 

PMID- 25998473
TI  - Arthroscopic Arthrodesis of the Distal Tibiofibular Syndesmosis.
AB  - Chronic syndesmosis disruption can occur if an acute lesion is missed or
      inadequately managed. This can result in significant functional deficit and
      development of post-traumatic ankle arthritis. Anatomic reduction of the
      syndesmosis and maintenance of the reduction by syndesmotic screw fixation alone,
      ligamentous reconstruction, or fusion of the syndesmosis are recommended. A
      technique of arthroscopic distal tibiofibular syndesmosis arthrodesis is
      described. 

PMID- 25998474
TI  - Lateral Hindfoot Impingement After Nonunion of Fracture of the Lateral Process of
      the Talus.
AB  - Fracture of the lateral process of the talus is a relatively uncommon ankle
      injury, and the diagnosis is easily delayed. Lateral hindfoot impingement is
      characteristically related to chronic hindfoot valgus malalignment, with lateral
      ankle pain localized to the subtalar region. In a review of the published data,
      lateral hindfoot impingement after nonunion of fracture of the lateral process of
      the talus was not found. We present the case of a patient with such an injury.
      The patient was treated operatively and was followed for 18 months.

PMID- 25998475
TI  - Ankle Joint Fusion With an Anatomically Preshaped Anterior Locking Plate.
AB  - We present a novel fixation plate for primary ankle joint fusion. A single
      anatomically preshaped angular stable plate was used with an anterior approach.
      An excellent result with good bone consolidation was present at the 1-year follow
      up examination. 

PMID- 25998476
TI  - A Modified Suture Bridge Technique for Application With Bone Anchors in Foot and
      Ankle Surgery.
AB  - We present a suture bridge technique for reattachment of tendon or ligament to
      bone for use in foot and ankle surgery. The method is a simple, strong, and
      reproducible technique that could decrease the risk of irritation of the
      overlying cutaneous barrier and minimizes the likelihood of tendon strangulation
      when combined with soft tissue bone anchors. The present report serves as a guide
      to the use of this suture technique for reattachment of the Achilles tendon. 

PMID- 25998477
TI  - Technique of Dorsal Transversely Oriented Transposition Flap for Web
      Reconstruction in Toe Syndactyly Surgery.
AB  - In toe desyndactyly, a dorsal or plantar commissural flap, combined with skin
      grafts, will ensure an acceptable result. However, the parallel unsightly scars
      in the longitudinal direction on the dorsum of the toes will sometimes fail to
      satisfy the patient's and/or the parents' aesthetic expectations. To address this
      issue, we developed a technique using a transversely oriented transposition flap
      for web reconstruction, which can spare the dorsal interdigital skin maximally to
      shift the dorsal scars plantarly such that they become inconspicuous. The design
      of the flap is simple and uncomplicated surgically. Moreover, the donor site
      morbidity is minimal, owing to the good healing potential of the transverse
      scars. This technique could be an alternative in web reconstruction of toe
      desyndactyly, especially in cases with high cosmetic priority. 

PMID- 25998478
TI  - Prevalence and Role of a Low-Lying Peroneus Brevis Muscle Belly in Patients With
      Peroneal Tendon Pathologic Features: A Potential Source of Tendon Subluxation.
AB  - A peroneus brevis low-lying muscle belly (LLMB) is a rare anomaly. A few
      published studies have supported the presence of this anomaly as an etiology for
      a peroneal tendon tear. However, the association between a peroneus brevis LLMB
      and tendon subluxation has not been well explored. In the present retrospective
      study, the magnetic resonance imaging (MRI) and intraoperative findings of 50
      consecutive patients undergoing primary peroneal tendon surgery during a 5-year
      period were assessed. The sensitivity and specificity of MRI compared with the
      intraoperative findings for identifying peroneal tendon disease were
      investigated. The presence of associated peroneal tendon pathologic features in
      patients with and without a peroneus brevis LLMB was also compared. The
      sensitivity of MRI was high for identifying peroneal tenosynovitis (81.58%) and
      tear (85.71%). Although the sensitivity of MRI for detecting a peroneus brevis
      LLMB (3.23%) and tendon subluxation (10.00%) was low, MRI had high specificity at
      94.74% and 100%, respectively. Intraoperatively, a peroneus brevis LLMB was seen
      in 62.00% of the patients with chronic lateral ankle pain and was associated with
      64.52% of the patients with tenosynovitis, 29.03% of those with tendon
      subluxation, and 80.65% of those with a peroneus brevis tendon tear. Although the
      presence of a peroneus brevis LLMB did not show any statistically significant
      association with peroneus brevis tendon subluxation, of the 10 patients with
      intraoperatively observed tendon subluxation, 9 had a concomitant peroneus brevis
      LLMB. More studies with larger patient populations are needed to better
      investigate the role of a peroneus brevis LLMB as a mass-occupying lesion
      resulting in peroneal tendon subluxation. 

PMID- 25998479
TI  - Callus Distraction Versus Single-Stage Lengthening With Bone Graft for Treatment
      of Brachymetatarsia: A Systematic Review.
AB  - Brachymetatarsia deformity is a cosmetically displeasing anomaly that can become
      physically symptomatic. The surgical techniques most commonly used to repair the
      anomaly include single-stage lengthening with a bone graft, callus distraction,
      or a combination of bone grafting and callus distraction. A systematic review of
      the published data was performed to compare the outcomes of these 3 surgical
      procedures. A total of 61 studies reporting the use of callus distraction or
      single-stage lengthening, or both, for the treatment of brachymetatarsia were
      included in the present review. The incidence of major postoperative
      complications after callus distraction, single-stage lengthening, and the
      combination procedure was 49 (12.62%), 13 (3.72%), and 3 (33.33%), respectively.
      The number of minor complications with callus distraction, single-stage
      lengthening, and the combination procedure was 152 (39.18%), 55 (15.76%), and 1
      (11.11%); the mean percentage of the original length achieved was 37.36%, 25.98%
      and 36.00%; and the mean length achieved was 17.5, 13.2, and 14.0 mm,
      respectively. The healing index (mo/cm) and healing time was 2.31 and 16.04
      weeks, 1.90 and 9.35 weeks, and 3.93 and 14.62 weeks for callus distraction,
      single-stage lengthening, and the combination procedure, respectively. Our
      findings indicate that the callus distraction technique is associated with
      greater length gained but results in greater complication rates and requires
      almost twice the time to heal. Single-stage lengthening with a bone graft was
      associated with fewer complications and faster healing times than callus
      distraction but with lesser gains in length. From the information reported in the
      studies we reviewed, the prevalence of bilateral brachymetatarsia was 44.52%, and
      the female/male ratio was 13.7:1. Both of these findings seem to contradict the
      usual data given (72% for bilateral brachymetatarsia and a female/male ratio of
      25:1). 

PMID- 25998480
TI  - Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube
      formation through the inactivation of mitogenic signaling pathways and regulation
      of vascular endothelial cadherin distribution and matrix metalloproteinase
      expression.
AB  - Ligularia fischeri (LF) has been used as an edible herb and traditional medicine
      for the treatment of inflammatory and infectious diseases. In the present study,
      we report the effects and molecular mechanism of the ethanolic extract of LF on
      cell proliferation, invasion and tube formation in human umbilical vein
      endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was
      accompanied by reduced expression of cell cycle-related proteins such as cyclin
      dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G1
      phase cell cycle arrest. We also show that LF treatment inhibited cell invasion
      and tube formation in HUVECs. These anti-angiogenic activities of LF were
      associated with the inactivation of mitogenic signaling pathways, induction of
      vascular endothelial (VE)-cadherin distribution at cell-cell contacts and
      inhibition of matrix metalloproteinase (MMP) expression. Collectively, our
      findings demonstrate the pharmacological functions and molecular mechanisms of LF
      in regulating endothelial cell fates, and support further development as a
      potential therapeutic agent for the treatment and prevention of angiogenesis
      related disorders including cancer. 

PMID- 25998482
TI  - Laparoscopy Assisted Transgastric Endoscopic Retrograde Cholangiopancreatography
      for the Management of Choledocholithiasis in a Patient With Roux-en-Y Gastric
      Bypass.

PMID- 25998481
TI  - Preserved pharmacokinetic exposure and distinct glycemic effects of insulin
      degludec and liraglutide in IDegLira, a fixed-ratio combination therapy.
AB  - Insulin degludec/liraglutide (IDegLira) is a novel fixed-ratio combination of the
      basal insulin insulin degludec (IDeg) and liraglutide, a glucagon-like peptide-1
      analog. The pharmacokinetics (PK) and pharmacodynamics of IDegLira were assessed
      versus its components. A single-dose, randomized, 4-period crossover clinical
      pharmacology study in healthy subjects compared the bioavailability of IDegLira
      with its monocomponents. Dose proportionality, covariate effects on exposure, and
      exposure-response for change in glycated hemoglobin were analyzed based on data
      from a randomized treat-to-target phase 3 study in subjects with type 2 diabetes.
      Overall, the PK properties of IDeg and liraglutide were preserved for IDegLira.
      Liraglutide exposure was lower when dosed as IDegLira but met the criterion for
      equivalence. No relevant deviations from dose proportionality for the IDegLira
      components were observed. Covariate effects on exposure were consistent with
      previous results. Glycemic response to IDegLira was larger than with IDeg or
      liraglutide alone, reflecting their distinct glucose-lowering effects throughout
      the dose/exposure range. 

PMID- 25998483
TI  - Behavioural Repertoires and Time Budgets of Semi-Free-Ranging and Captive Groups
      of Wedge-Capped Capuchin Monkeys, Cebus olivaceus, in Zoo Exhibits in Venezuela.
AB  - The behavioural repertoires and time budgets of 2 captive groups and 1 semi-free
      ranging group of Cebus olivaceus were determined with the aim to assess the
      impact of the zoo environment on behaviour. The repertoires were qualitatively
      similar between groups and to those reported for wild troops, but the captive
      groups showed self-directed and stereotyped behaviours not reported in the wild.
      The differences in repertoires between groups were easily associated with the
      opportunity to interact directly with the visitors, with particularities of the
      enclosure and with the severity of confinement. Overall, females spent more time
      foraging than males in the 2 captive groups, and adults rested and watched more
      than subadults in all the groups. Time budgets were dominated by foraging,
      resting, movement and affiliative interactions, but their relative importance
      varied between groups, with foraging being especially prominent in the most
      confined group. The time budgets also varied qualitatively from those reported
      for wild troops. We conclude the species is behaviourally able to adjust to
      captivity, but the slight differences along the continuum from wild to semi-free
      to captive are suggestive of mild stress or social tension probably due to
      unstimulating environmental conditions, high visitor pressure and deviations from
      typical sex-age group composition.

PMID- 25998484
TI  - Association of Macrophage Migration Inhibitory Factor Polymorphisms with
      Gestational Diabetes Mellitus in Han Chinese Women.
AB  - OBJECTIVE: The purpose of the study was to investigate the association between
      macrophage migration inhibitory factor (MIF) gene polymorphisms and gestational
      diabetes mellitus (GDM) in Han Chinese women. METHODS: In this study, 915
      unrelated pregnant women were recruited, among whom 430 had GDM and 485 served as
      controls. The rs755622 in the MIF gene (MIF-173G/C) was detected by the
      polymerase chain reaction Tm-shift genotyping method with fluorescence melting
      curve analysis. The associations of rs755622 in MIF variants with plasma glucose
      and insulin levels in the oral glucose tolerance test (OGTT) as well as with with
      blood fat levels were investigated. RESULTS: The frequencies of genotypes and
      allele types of rs755622 in MIF were significantly different between women of the
      GDM and control groups (all p < 0.001). Moreover, the single nucleotide
      polymorphism (SNP) was significantly associated with increased glucose levels at
      0, 60 and 120 min during the OGTT (all p < 0.0038) and with the increased
      homeostasis model assessment of insulin resistance (p < 0.001) in the GDM group.
      CONCLUSION: Genetic polymorphism of rs755622 in MIF is associated with increased
      risk of GDM and insulin resistance in Han Chinese women.

PMID- 25998485
TI  - A systematic approach to standardize artificial aging of resin composite cements.
AB  - OBJECTIVE: The aim of the investigation was to contribute to the ongoing
      discussion at the international standardization committee on how to artificially
      age dental resin composite cements. METHODS: Indirect tensile strength (n=30) of
      a dual-cured resin composite cement (Panavia F2.0) was measured to evaluate the
      effect of water storage at 37 degrees C or thermal cycling (5 degrees C/55
      degrees C/1min) for up to 64 days. The influence of water temperature (5-65
      degrees C) after 16 days and the effect of 1 day water storage at 37 degrees C
      prior to aging were assessed. Storage in air at 37 degrees C served as control.
      RESULTS: Thermal cycling affected the indirect tensile strength most, followed by
      water storage at 55 degrees C, whereas water storage at 37 degrees C had only
      little influence. Major deterioration occurred before day 4 (~6000 cycles). A 1
      day pre-treatment by water storage at 37 degrees C prior to thermal cycling
      attenuated the effect of aging. SIGNIFICANCE: For the material investigated,
      thermal cycling for 4 days is the most efficient aging procedure. A 1-day water
      storage at 37 degrees C prior to thermal cycling is recommended to allow complete
      polymerization. A 4-day water storage at 55 degrees C may be considered as a
      viable alternative to thermal cycling.

PMID- 25998486
TI  - Curriculum design: Can we learn from product lifecycle management?

PMID- 25998487
TI  - Protein localization vector propagation: a method for improving the accuracy of
      drug repositioning.
AB  - Identifying alternative indications for known drugs is important for the
      pharmaceutical industry. Many computational methods have been proposed for
      predicting unknown associations between drugs and target proteins associated with
      diseases. To produce better prediction, researchers should not only develop
      accurate algorithms but identify good features that reflect intracellular
      systems. In this paper, we proposed a novel method for exploiting protein
      localization. We generated localization vectors (LVs) from protein localization
      and propagated LVs through a protein interaction network to increase the coverage
      of the localization information. The LVs showed distinct patterns among targets
      of known drugs as well as independent characteristics compared to existing
      features. Based on the experimental results, we determined that including LVs
      improves cross-validation accuracy and, produces better novel predictions with
      real and independent clinical trial data. Moreover, the propagation of LVs showed
      a positive result that it can help in increasing the coverage of the prediction
      results. 

PMID- 25998488
TI  - Ecological Assessment Battery for Numbers (EABN) for brain-damaged patients:
      standardization and validity study.
AB  - OBJECTIVES: Number-processing may be altered following brain injury and might
      affect the everyday life of patients. We developed the first ecological tool to
      assess number-processing disorders in brain-injured patients, the Ecological
      Assessment Battery for Numbers (EABN; in French, the BENQ). The aim of the
      present study was to standardize and validate this new tool. MATERIAL AND
      METHODS: Standardization included 126 healthy controls equally distributed by
      age, sex and sociocultural level. First, 17 patients were evaluated by the EABN;
      then scores for a subgroup of 10 were compared with those from a French
      analytical calculation test, the Evaluation Clinique des Aptitudes Numeriques
      (ECAN). The concordance between the EABN and the ECAN was analyzed to determine
      construct validity. Discrimination indexes were calculated to assess the
      sensitivity of the subtests. RESULTS: Standardization highlighted a major effect
      of sociocultural level. In total, 9 of 17 patients had a pathological EABN score,
      with difficulties in telling time, making appointments and reading numerical
      data. The results of both the EABN and ECAN tests were concordant (Kendall's
      w=0.97). Finally, the discriminatory power was good, particularly for going to
      the movies, cheque-writing and following a recipe: scores were>0.4. CONCLUSION:
      The EABN is a new tool to assess number-processing disorders in adults. This tool
      has been standardized and has good psychometric properties for patients with
      brain injury.

PMID- 25998489
TI  - Novel relationships between oxidative stress and angiogenesis-related factors in
      sepsis: New biomarkers and therapies.
AB  - Sepsis is a systemic uncontrolled inflammatory response in the presence of an
      infection. It remains a major cause of morbidity and mortality in hospitalized
      patients. According to its severity, sepsis can progress to three different
      states: severe sepsis, septic shock, and multiple organ dysfunction syndrome,
      related to organ dysfunction and/or tissue hypoperfusion. Different processes
      underlie its pathophysiology; among them are oxidative stress, endothelial and
      mitochondrial dysfunction, and angiogenesis-related factors. However, no studies
      have integrated these elements in sepsis. The main difficulty in sepsis is its
      diagnosis. Currently, the potential of inflammatory biomarkers in septic patients
      remains weak. In this context, the research into new biomarkers is essential to
      aid with sepsis diagnosis and prognostication. Furthermore, even though the
      current management of severe forms of sepsis has been effective, morbimortality
      remains elevated. Therefore, it is essential to explore alternative approaches to
      therapy development. The aim of this review is to present an update of evidence
      supporting the role of oxidative stress and angiogenesis-related factors in the
      pathophysiology of the different forms of sepsis. It proposes a novel convergence
      between both elements in their role in the disease, and it will cover their
      utility as new diagnostic tools, predictors of outcome, and as novel therapeutic
      targets. 

PMID- 25998491
TI  - Associated and dissociated neural substrates of aesthetic judgment and aesthetic
      emotion during the appreciation of everyday designed products.
AB  - The aesthetics of designed products have become part of our life in modern
      society. This study explores the neural mechanisms of how aesthetic judgment and
      aesthetic emotion interplay during the appreciation of designed products that are
      commonly seen in daily life. Participants were 30 college students, and the
      stimuli were 90 pictures of everyday designed products. Based on an event-related
      paradigm, the findings of this study suggest that there are associative and
      dissociative neutral mechanisms underlying different types of aesthetic judgment
      and aesthetic emotion. The study identified the following main findings: (a)
      normative beauty and subjective beauty both involved the left anterior cingulate
      cortex (ACC); (b) subjective beauty and positive emotion both involved the right
      ACC; (c) subjective beauty and negative emotion both involved the precuneus; (d)
      subjective ugliness and negative emotion both involved the right inferior frontal
      gyrus; (e) subjective ugliness alone additionally activated the insula; and (f)
      subjective beauty alone additionally activated the caudate. The findings in this
      study shed light on complex but ordinary processes of aesthetic appreciation. 

PMID- 25998490
TI  - Osteopontin mediates survival, proliferation and migration of neural stem cells
      through the chemokine receptor CXCR4.
AB  - INTRODUCTION: Osteopontin (OPN) is a phosphoglycoprotein with important roles in
      tissue homeostasis, wound healing, immune regulation, and stress responses. It is
      expressed constitutively in the brain and upregulated during neuroinflammatory
      responses; for example, after focal cerebral ischemia. To date, its effects on
      neural stem cells (NSC) remain to be elucidated and are, accordingly, the subject
      of this study. METHOD: Primary fetal rat NSC were cultured as homogenous
      monolayers and treated with different concentrations of OPN. Fundamental
      properties of NSC were assessed following OPN exposure, including proliferative
      activity, survival under oxidative stress, migration, and differentiation
      potential. To elucidate a putative action of OPN via the CXC chemokine receptor
      type 4 (CXCR4), the latter was blocked with AMD3100. To investigate effects of
      OPN on endogenous NSC in vivo, recombinant OPN was injected into the brain of
      healthy adult rats as well as rats subjected to focal cerebral ischemia. Effects
      of OPN on NSC proliferation and neurogenesis in the subventricular zone were
      studied immunohistochemically. RESULTS: OPN dose-dependently increased the number
      of NSC in vitro. As hypothesized, this effect was mediated through CXCR4. The
      increase in NSC number was due to both enhanced cell proliferation and increased
      survival, and was confirmed in vivo. Additionally, OPN dose-dependently
      stimulated the migration of NSC via CXCR4. Moreover, in the presence of OPN,
      differentiation of NSC led to a significant increase in neurogenesis both in
      vitro as well as in vivo after cerebral ischemia. CONCLUSION: Data show positive
      effects of OPN on survival, proliferation, migration, and neuronal
      differentiation of NSC. At least in part these effects were mediated via CXCR4.
      Results suggest that OPN is a promising substance for the targeted activation of
      NSC in future experimental therapies for neurological disorders such as stroke.

PMID- 25998492
TI  - Parietal lesion effects on cued recall following pair associate learning.
AB  - We investigated the involvement of the posterior parietal cortex in episodic
      memory in a lesion-effects study of cued recall following pair-associate
      learning. Groups of patients who had experienced first-incident stroke, generally
      in middle cerebral artery territory, and exhibited damage that included lateral
      posterior parietal regions, were tested within an early post-stroke time window.
      In three experiments, patients and matched healthy comparison groups executed
      repeated study and cued recall test blocks of pairs of words (Experiment 1),
      pairs of object pictures (Experiment 2), or pairs of object pictures and
      environmental sounds (Experiment 3). Patients' brain CT scans were subjected to
      quantitative analysis of lesion volumes. Behavioral and lesion data were used to
      compute correlations between area lesion extent and memory deficits, and to
      conduct voxel-based lesion-symptom mapping. These analyses implicated lateral
      ventral parietal cortex, especially the angular gyrus, in cued recall deficits,
      most pronouncedly in the cross-modal picture-sound pairs task, though significant
      parietal lesion effects were also found in the unimodal word pairs and picture
      pairs tasks. In contrast to an earlier study in which comparable parietal lesions
      did not cause deficits in item recognition, these results indicate that lateral
      posterior parietal areas make a substantive contribution to demanding forms of
      recollective retrieval as represented by cued recall, especially for complex
      associative representations. 

PMID- 25998493
TI  - Pelvic-Floor-Muscle Training Adherence: Tools, Measurements and Strategies-2011
      ICS State-of-the-Science Seminar Research Paper II of IV.
AB  - AIMS: This paper on pelvic-floor-muscle training (PFMT) adherence, the second of
      four from the International Continence Society's 2011 State-of-the-Science
      Conference, aims to (1) identify and collate current adherence outcome measures,
      (2) report the determinants of adherence, (3) report on PFMT adherence
      strategies, and (4) make actionable clinical and research recommendations.
      METHOD: Data were amassed from a literature review and an expert panel (2011
      conference), following consensus statement methodology. Experts in pelvic floor
      dysfunction collated and synthesized the evidence and expert opinions on PFMT
      adherence for urinary incontinence (UI) and lower bowel dysfunction in men and
      women and pelvic organ prolapse in women. RESULTS: The literature was scarce for
      most of the studied populations except for limited research on women with UI.
      OUTCOME MEASURES: Exercise diaries were the most widely-used adherence outcome
      measure, PFMT adherence was inconsistently monitored and inadequately reported.
      Determinants: Research, mostly secondary analyses of RCTs, suggested that
      intention to adhere, self-efficacy expectations, attitudes towards the exercises,
      perceived benefits and a high social pressure to engage in PFMT impacted
      adherence. STRATEGIES: Few trials studied and compared adherence strategies. A
      structured PFMT programme, an enthusiastic physiotherapist, audio prompts, use of
      established theories of behavior change, and user-consultations seem to increase
      adherence. CONCLUSION: The literature on adherence outcome measures, determinants
      and strategies remains scarce for the studied populations with PFM dysfunction,
      except in women with UI. Although some current adherence findings can be applied
      to clinical practice, more effective and standardized research is urgently needed
      across all the sub-populations.

PMID- 25998494
TI  - Role of different vehicles in carotenoids delivery and their influence on cell
      viability, cell cycle progression, and induction of apoptosis in HeLa cells.
AB  - The objective of the present study was to determine the role of different
      vehicles in carotenoids delivery and their influence on cell viability, cell
      cycle progression and induction of apoptosis in HeLa cells. Cells (5 * 10(3))
      were treated with different concentrations (25-100 uM) of beta-carotene (BC) or
      lutein (L) or astaxanthin (AST) dissolved in 0.5% of tetrahydrofuran (THF),
      dimethylsulfoxide (DMSO), and fetal bovine serum (FBS), respectively. The effect
      of delivery vehicle on carotenoids uptake, cytotoxicity, oxidative status, cell
      cycle distribution, and apoptosis was examined after 48 h of incubation. The
      results shown that, cell viability reduced significantly in a dose- and time
      dependent manner irrespective of carotenoid delivered in vehicles. Cellular
      uptake of BC delivered in THF was higher by 49.1, 29.7% and L delivered through
      THF was higher by 41.7 and 37.5% than DMSO and FBS, respectively. While, AST
      delivered through DMSO was higher by 36.1 and 43.7% than the THF and FBS,
      respectively. In case of cells treated either with BC or L delivered through THF
      and AST in DMSO decreased the glutathione and increased the malondialdehyde
      levels. The net increase in the G 2/M phase percentage of cell cycle progression
      was observed in carotenoid-treated cells. The % induction of apoptosis by BC or L
      delivered with THF and AST in DMSO was higher than other treated groups. In
      conclusion, choice of suitable vehicle for specific carotenoids delivery is
      essential that in turn may influence on cell proliferation and cell-based assays.

PMID- 25998496
TI  - HuangQi Decoction Improves Renal Tubulointerstitial Fibrosis in Mice by
      Inhibiting the Up-Regulation of Wnt/beta-Catenin Signaling Pathway.
AB  - OBJECT: To explore the effects of HuangQi decoction on tubulointerstitial
      fibrosis in mice and the Wnt/beta-catenin signaling pathway. METHODS: Unilateral
      ureteral obstruction (UUO) model was used. A total of 120 C57/BL mice were
      randomly divided into 6 groups, sham group, sham+HuangQi decoction group (1.08
      g/kg), UUO group, UUO+HuangQi decoction group (0.12, 0.36, 1.08 g/kg).
      Immunohistochemical analysis, RT-PCR and Western blot were employed to examine
      the proteins and genes related to the Wnt/beta-catenin signaling pathway.
      RESULTS: In UUO mice models, expression levels of Wnt3,4, Frizzled4, LRP5,6, beta
      catenin, LEF-1, TCF-1, Snail, MMP2,7 genes were positively correlated with the
      degree of renal tubulointerstitial fibrosis, while expression levels of GSK
      3beta, Axin, APC, CK1 were negatively correlated. HuangQi decoction could down
      regulate expression levels of Wnt3,4, Frizzled4, LRP5,6, beta-catenin, LEF-1, TCF
      1, Snail, Twist, MMP2,7 and up-regulate expression levels of GSK-3beta, Axin,
      APC, CK1 and E-cadherin. CONCLUSION: HuangQi decoction could effectively inhibit
      the up-regulation of Wnt/beta-catenin signaling pathway induced by UUO, implying
      a possible role in improving renal interstitial fibrosis.

PMID- 25998495
TI  - Electrophysiological assessment of retinal ganglion cell function.
AB  - The function of retinal ganglion cells (RGCs) can be non-invasively assessed in
      experimental and genetic models of glaucoma by means of variants of the ERG
      technique that emphasize the activity of inner retina neurons. The best
      understood technique is the Pattern Electroretinogram (PERG) in response to
      contrast-reversing gratings or checkerboards, which selectively depends on the
      presence of functional RGCs. In glaucoma models, the PERG can be altered before
      histological loss of RGCs; PERG alterations may be either reversed with moderate
      IOP lowering or exacerbated with moderate IOP elevation. Under particular
      luminance-stimulus conditions, the Flash-ERG displays components that may reflect
      electrical activity originating in the proximal retina and be altered in some
      experimental glaucoma models (positive Scotopic Threshold response, pSTR;
      negative Scotopic Threshold Response, nSTR; Photopic Negative Response, PhNR;
      Oscillatory Potentials, OPs; multifocal ERG, mfERG). It is not yet known which of
      these components is most sensitive to glaucomatous damage. Electrophysiological
      assessment of RGC function appears to be a necessary outcome measure in
      experimental glaucoma models, which complements structural assessment and may
      even predict it. Neuroprotective strategies could be tested based on enhancement
      of baseline electrophysiological function that results in improved RGC survival.
      The use of electrophysiology in glaucoma models may be facilitated by
      specifically designed instruments that allow high throughput, robust assessment
      of electrophysiological function. 

PMID- 25998497
TI  - Heterozygous Deletion of KLHL1/ATX8OS at the SCA8 Locus Is Unlikely Associated
      With Cerebellar Impairment in Humans.

PMID- 25998498
TI  - Effect of Presurgical Iodine-Based Disinfection on Bacterial Colonization of the
      Equine Peripodal Region.
AB  - OBJECTIVE: To compare bacterial colonization after diluted iodine tincture or
      povidone iodine solution for presurgical disinfection of the equine peripodal
      region. STUDY DESIGN: Complete block design. ANIMALS: Five horses. METHODS:
      Disinfection protocols using iodine tincture or povidone iodine solutions were
      tested on 5 pairs (n = 10) equine front feet. Iodine tincture was applied to the
      left feet and povidone iodine to the right feet. Fixed surfaces of the sole,
      frog, hoof wall, and peripodal skin were swabbed pre-preparation (T0), after a
      standard pre-disinfection step (T1), after short disinfection with a 4-minute
      application of 0.5% iodine tincture or povidone iodine (T2), and after long
      disinfection with 12-hour soaking in 0.25% iodine tincture or povidone iodine
      (T3). Quantitative bacteriology was performed on each swab. RESULTS: The frog and
      sole were the most contaminated sites compared to hoof wall and skin at T0.
      Bacterial counts were significantly decreased at T2 for both solutions. Bacterial
      counts did not change significantly with iodine tincture at T3 but increased with
      povidone iodine compared to T2. Skin abrasions were detected on almost all feet
      but were subjectively more severe on iodine tincture-treated feet. CONCLUSION:
      Soaking for 12 hours with either iodine tincture or povidone iodine is not
      recommended as these solutions damaged the skin and bacterial recolonization was
      noted with povidone iodine. Four-minute disinfection using either iodine tincture
      or povidone iodine (0.5% available iodine) is appropriate for presurgical
      preparation of the equine peripodal region.

PMID- 25998499
TI  - Whole-genome sequencing for outbreak investigations of methicillin-resistant
      Staphylococcus aureus in the neonatal intensive care unit: time for routine
      practice?
AB  - BACKGROUND Infants in the neonatal intensive care unit (NICU) are at increased
      risk for methicillin-resistant Staphylococcus aureus (MRSA) acquisition.
      Outbreaks may be difficult to identify due in part to limitations in current
      molecular genotyping available in clinical practice. Comparison of genome-wide
      single nucleotide polymorphisms (SNPs) may identify epidemiologically distinct
      isolates among a population sample that appears homogenous when evaluated using
      conventional typing methods. OBJECTIVE To investigate a putative MRSA outbreak in
      a NICU utilizing whole-genome sequencing and phylogenetic analysis to identify
      recent transmission events. DESIGN Clinical and surveillance specimens collected
      during clinical care and outbreak investigation. PATIENTS A total of 17 neonates
      hospitalized in a 43-bed level III NICU in northeastern Florida from December
      2010 to October 2011 were included in this study. METHODS We assessed
      epidemiological data in conjunction with 4 typing methods: antibiograms, PFGE,
      spa types, and phylogenetic analysis of genome-wide SNPs. RESULTS Among the 17
      type USA300 isolates, 4 different spa types were identified using pulsed-field
      gel electrophoresis. Phylogenetic analysis identified 5 infants as belonging to 2
      clusters of epidemiologically linked cases and excluded 10 unlinked cases from
      putative transmission events. The availability of these results during the
      initial investigation would have improved infection control interventions.
      CONCLUSION Whole-genome sequencing and phylogenetic analysis are invaluable tools
      for epidemic investigation; they identify transmission events and exclude cases
      mistakenly implicated by traditional typing methods. When routinely applied to
      surveillance and investigation in the clinical setting, this approach may provide
      actionable intelligence for measured, appropriate, and effective interventions.

PMID- 25998500
TI  - Febuxostat improves endothelial function in hemodialysis patients with
      hyperuricemia: A randomized controlled study.
AB  - Endothelial dysfunction is often found in both hyperuricemia and hemodialysis
      patients. Recent studies have shown that treating hyperuricemia with allopurinol
      improves endothelial dysfunction. This study is performed to assess the effect of
      febuxostat on endothelial dysfunction in hemodialysis patients with
      hyperuricemia. We randomly assigned 53 hemodialysis patients with hyperuricemia
      to a febuxostat (10 mg daily) group and a control group and measured flow
      mediated dilation, serum uric acid (UA) levels, systolic and diastolic blood
      pressure, malondialdehyde-modified low-density lipoprotein (MDA-LDL), and highly
      sensitive C-reactive protein (hsCRP) at baseline and at the end of a 4-week study
      period. Flow-mediated dilation increased from 5.3% +/- 2.4% to 8.9% +/- 3.6% in
      the febuxostat group but did not change significantly in the control group.
      Treatment with febuxostat resulted in a significant decrease in serum UA level
      and a significant decrease in MDA-LDL compared with baseline, but no significant
      difference was observed in hsCRP level or blood pressure. No significant
      differences were observed in the control group. Febuxostat improved endothelial
      dysfunction and reduced serum UA levels and oxidative stress in hemodialysis
      patients with hyperuricemia. 

PMID- 25998501
TI  - Design, synthesis and pharmacology of 1,1-bistrifluoromethylcarbinol derivatives
      as liver X receptor beta-selective agonists.
AB  - A novel series of 1,3-bistrifluoromethylcarbinol derivatives that act as liver X
      receptor (LXR) beta-selective agonists was discovered. Structure-activity
      relationship studies led to the identification of molecule 62, which was more
      effective (Emax) and selective toward LXRbeta than T0901317 and GW3965.
      Furthermore, 62 decreased LDL-C without elevating the plasma TG level and
      significantly suppressed the lipid-accumulation area in the aortic arch in a Bio
      F1B hamster fed a diet high in fat and cholesterol. We demonstrated that our
      LXRbeta agonist would be potentially useful as a hypolipidemic and anti
      atherosclerotic agent. In this manuscript, we report the design, synthesis and
      pharmacology of 1,3-bistrifluoromethylcarbinol derivatives. 

PMID- 25998502
TI  - Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore
      space (JPS) and ensemble docking.
AB  - Joint pharmacophore space (JPS), ensemble docking and sequential JPS-ensemble
      docking were used to select three panels of compounds (10 per panel) for
      evaluation as LRRK2 inhibitors. These computational methods identified four LRRK2
      inhibitors with IC50 values <12MUM. The sequential JPS-ensemble docking predicted
      the majority of active hits. One of the inhibitors (Z-8205) identified using this
      method was also found to inhibit the G2019S mutant of LRRK2 25-fold better than
      wild-type enzyme. This bias for the G2019S mutant is proposed to arise from an
      interaction with S2019 in this form of the enzyme. In addition, Z-8205 was found
      to only inhibit one other kinase when profiled against a panel of 97 kinases at
      10MUM. 

PMID- 25998503
TI  - Activity and anion inhibition studies of the alpha-carbonic anhydrase from
      Thiomicrospira crunogena XCL-2 Gammaproteobacterium.
AB  - Thiomicrospira crunogena XCL-2 expresses an alpha-carbonic anhydrase (TcruCA).
      Sequence alignments reveal that TcruCA displays a high sequence identity (>30%)
      relative to other alpha-CAs. This includes three conserved histidines that
      coordinate the active site zinc, a histidine proton shuttling residue, and
      opposing hydrophilic and hydrophobic sides that line the active site. The
      catalytic efficiency of TcruCA is considered moderate relative to other alpha-CAs
      (k(cat)/K(M)=1.1*10(7) M(-1) s(-1)), being a factor of ten less efficient than
      the most active alpha-CAs. TcruCA is also inhibited by anions with Cl(-), Br(-),
      and I(-), all showing Ki values in the millimolar range (53-361 mM). Hydrogen
      sulfide (HS(-)) revealed the highest affinity for TcruCA with a Ki of 1.1 MUM. It
      is predicted that inhibition of TcruCA by HS(-) (an anion commonly found in the
      environment where Thiomicrospira crunogena is located) is a way for
      Thiomicrospira crunogena to regulate its carbon-concentrating mechanism (CCM) and
      thus the organism's metabolic functions. Results from this study provide
      preliminary insights into the role of TcruCA in the general metabolism of
      Thiomicrospira crunogena.

PMID- 25998504
TI  - Synthesis and antiproliferative activity of some novel benzo-fused
      imidazo[1,8]naphthyridinones.
AB  - A number of new substituted fused naphthyridinones has been prepared and their
      antiproliferative activity was evaluated against a panel of seven human tumor
      cell lines, including the variant MES-SA/Dx5, reported to be 100-fold resistant
      to doxorubicin. Certain derivatives exhibited interesting cytotoxic properties,
      possessing IC50 values in a low MUM range. 

PMID- 25998505
TI  - Removal of Dabigatran Is Superior by Sustained Low Efficient Dialysis (SLED)
      Compared to Intermittent Hemodialysis.

PMID- 25998506
TI  - Monitoring organic reactions by UF-NMR spectroscopy.
AB  - Standard 2D NMR experiments suffer from the many t1 increments needed for spectra
      with sufficient digital resolution in the indirect dimension. Despite the
      different methodological approaches to overcome this problem, these increments
      have prevented studies of fast reactions. The development of ultrafast NMR (UF
      NMR) has decisively speeded up the time scale of standard NMR to allow the study
      of organic reactions as they happen in real time to reveal mechanistic details.
      This mini-review summarizes the results achieved in monitoring organic reactions
      through this exciting technique.

PMID- 25998507
TI  - High yield synthesis of high-silica chabazite by combining the role of zeolite
      precursors and tetraethylammonium: SCR of NOx.
AB  - The synthesis of chabazite with high solid yields is achieved by the rational
      combination of directing effects of a source of Si and Al coming from USY
      zeolites and the inexpensive tetraethylammonium. Moreover, Cu-CHA materials
      prepared by post-synthetic and "one-pot" methodologies show high activity and
      stability for SCR of NOx. 

PMID- 25998508
TI  - Piwi-Interacting RNAs (piRNAs) Are Dysregulated in Renal Cell Carcinoma and
      Associated with Tumor Metastasis and Cancer-Specific Survival.
AB  - Piwi-interacting RNAs (piRNAs) are a distinct group of small noncoding RNAs
      (sncRNAs) that silence transposable genetic elements to protect genome integrity.
      Because of their limited expression in gonads and sequence diversity, piRNAs
      remain the most mysterious class of small RNAs. Studies have shown piRNAs are
      present in somatic cells and dysregulated in gastric, breast and liver cancers.
      By deep sequencing 24 frozen benign kidney and clear cell renal cell carcinoma
      (ccRCC) specimens and using the publically available piRNA database, we found
      26,991 piRNAs present in human kidney tissue. Among 920 piRNAs that had at least
      two copies in one specimen, 19 were differentially expressed in benign kidney and
      ccRCC tissues, and 46 were associated with metastasis. Among the metastasis
      related piRNAs, we found three piRNAs (piR-32051, piR-39894 and piR-43607) to be
      derived from the same piRNA cluster at chromosome 17. We confirmed the three
      selected piRNAs not to be miRNAs or miRNA-like sncRNAs. We further validated the
      aberrant expression of the three piRNAs in a 68-case formalin-fixed and paraffin
      embedded (FFPE) ccRCC tissue cohort and showed the up-regulation of the three
      piRNAs to be highly associated with ccRCC metastasis, late clinical stage and
      poor cancer-specific survival. 

PMID- 25998509
TI  - Piwil 2 expression is correlated with disease-specific and progression-free
      survival of chemotherapy-treated bladder cancer patients.
AB  - Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The
      expression of Piwil 2 is associated with stem cells. A role in tumorigenesis
      and/or tumor progression is proposed for different cancers but not yet for
      bladder cancer (BCa). We investigated the Piwil 2 expression by
      immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and
      adjuvant chemotherapy. The association between Piwil 2 expression and disease
      specific (DSS) or progression-free survival (PFS) was calculated using Kaplan
      Meier analyses and univariate/multivariate Cox's regression hazard models.In a
      multivariate Cox's regression, Piwil 2 expression, either in the cytoplasm or the
      nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic
      staining pattern was associated with poor DSS and tumor progression (RR=2.7;
      P=0.004 and RR=2.4; P=0.027). Likewise,, absent nuclear Piwil 2 immunoreactivity
      was associated with poor DSS and tumor progression (RR=2.3; P=0.023 and RR=2.2;
      P=0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic
      and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related
      death (P=0.005) compared to patients with strong expression. Considering only
      patients with high grade G3 tumors, a 7.8-fold risk of tumor-associated death and
      a 3.6-fold risk of tumor progression were detected independently of the
      histologic tumor subtype or the chemotherapy regimen. In summary, a combination
      of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly
      associated with an increased risk of DSS and tumor progression. This implicates
      that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients. 

PMID- 25998510
TI  - Modular Transcriptional Networks of the Host Pulmonary Response during Early and
      Late Pneumococcal Pneumonia.
AB  - Streptococcus pneumoniae (Spneu) remains the most lethal bacterial pathogen and
      the dominant agent of community-acquired pneumonia. Treatment has perennially
      focused on the use of antibiotics, albeit scrutinized due to the occurrence of
      antibiotic-resistant Spneu strains. Immunomodulatory strategies have emerged as
      potential treatment options. Although promising, immunomodulation can lead to
      improper tissue functions either at steady state or upon infectious challenge.
      This argues for the availability of tools to enable a detailed assessment of
      whole pulmonary functions during the course of infection, not only those
      functions biased to the defense response. Thus, through the use of an unbiased
      tissue microarray and bioinformatics approach, we aimed to construct a
      comprehensive map of whole-lung transcriptional activity and cellular pathways
      during the course of pneumococcal pneumonia. We performed genome-wide
      transcriptional analysis of whole lungs before and 6 and 48 h after Spneu
      infection in mice. The 4,000 most variable transcripts across all samples were
      used to assemble a gene coexpression network comprising 13 intercorrelating
      modules (clusters of genes). Fifty-four percent of this whole-lung
      transcriptional network was altered 6 and 48 h after Spneu infection. Canonical
      signaling pathway analysis uncovered known pathways imparting protection,
      including IL17A/IL17F signaling and previously undetected mechanisms that
      included lipid metabolism. Through in silico prediction of cell types, pathways
      were observed to enrich for distinct cell types such as a novel stromal cell
      lipid metabolism pathway. These cellular mechanisms were furthermore anchored at
      functional hub genes of cellular fate, differentiation, growth and transcription.
      Collectively, we provide a benchmark unsupervised map of whole-lung
      transcriptional relationships and cellular activity during early and late
      pneumococcal pneumonia. 

PMID- 25998512
TI  - Prognostic impact of concordant and discordant bone marrow involvement and cell
      of-origin in Korean patients with diffuse large B-cell lymphoma treated with R
      CHOP.
AB  - AIMS: Previous studies have suggested many prognostic factors in diffuse large B
      cell lymphoma (DLBCL), but the prognostic importance of cell-of-origin and
      discordant bone marrow involvement remains unclear. The aim of this study was to
      evaluate the prognostic impact of bone marrow involvement histological subtype,
      cell-of-origin subtype and international prognostic index (IPI) scores in
      patients with DLBCL. METHODS: Patients who were newly diagnosed with DLBCL and
      treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and
      prednisone (R-CHOP) were analysed. Clinical information was reviewed
      retrospectively. Patients were classified into negative, concordant and
      discordant bone marrow involvement by histological review. The cell-of-origin
      types were defined using immunohistochemical analysis. RESULTS: Both concordant
      and discordant bone marrow involvement had a negative prognostic impact on
      progression-free survival, independent of the standard and National Comprehensive
      Cancer Network (NCCN) IPI scores and cell-of-origin. Patients with non-germinal
      centre B-cell type showed significantly shorter progression-free survival than
      those with germinal centre B-cell type. However, non-germinal centre B-cell type
      did not have a prognostic impact on progression-free survival or overall survival
      after controlling for the standard and NCCN-IPI and bone marrow involvement.
      CONCLUSIONS: Both concordant and discordant bone marrow involvement had an
      adverse prognostic impact on progression-free survival and overall survival; this
      was independent of the standard and NCCN-IPI and cell-of-origin (non-germinal
      centre B-cell type). The NCCN-IPI had more powerful prognostic value than the
      standard IPI (sIPI). The non-germinal centre B-cell type lost significant
      prognostic impact on progression-free survival after adjustment for standard and
      NCCN-IPI and bone marrow involvement.

PMID- 25998511
TI  - Methylene Blue Reduces Acute Cerebral Ischemic Injury via the Induction of
      Mitophagy.
AB  - The treatment of stroke is limited by a short therapeutic window and a lack of
      effective clinical drugs. Methylene blue (MB) has been used in laboratories and
      clinics since the 1890s. Few studies have reported the neuroprotective role of MB
      in cerebral ischemia-reperfusion injury. However, whether and how MB protects
      against acute cerebral ischemia (ACI) injury was unclear. In this study, we
      investigated the effect of MB on this injury and revealed that MB protected
      against ACI injury by augmenting mitophagy. Using a rat middle cerebral artery
      occlusion (MCAO) model, we demonstrated that MB improved neurological function
      and reduced the infarct volume and necrosis after ACI injury. These improvements
      depended on the effect of MB on mitochondrial structure and function. ACI caused
      the disorder and disintegration of mitochondrial structure, while MB ameliorated
      the destruction of mitochondria. In addition, mitophagy was inhibited at 24 h
      after stroke and MB augmented mitophagy. In an oxygen-glucose deprivation (OGD)
      model in vitro, we further revealed that the elevation of mitochondrial membrane
      potential (MMP) by MB under OGD conditions mediated the augmented mitophagy. In
      contrast, exacerbating the decline of MMP during OGD abolished the MB-induced
      activation of mitophagy. Taken together, MB promotes mitophagy by maintaining the
      MMP at a relatively high level, which contributes to a decrease in necrosis and
      an improvement in neurological function, thereby protecting against ACI injury. 

PMID- 25998513
TI  - Paediatric fibroepithelial lesions revisited: pathological insights.
AB  - AIM: To review the clinicopathological features of fibroepithelial neoplasms of
      the breast diagnosed by the paediatric pathology service in a children's
      hospital. METHODS: Files of the Department of Pathology and Laboratory Medicine,
      Kandang Kerbau Women's and Children's Hospital, were searched for breast
      fibroepithelial neoplasms diagnosed between January 2002 and December 2012.
      Tumour size and macroscopic findings were obtained from surgical pathology
      reports while clinical features were determined from clinical files. Histological
      slides were reviewed and microscopic parameters documented. Findings were
      tabulated and analysed using statistical methods. RESULTS: 68 fibroepithelial
      neoplasms from 53 female subjects were studied. There were 27 (39.7%)
      fibroadenomas, 32 (47.1%) juvenile fibroadenomas, 3 (4.4%) cellular
      fibroadenomas, 3 (4.4%) benign phyllodes tumours with the remaining 3 (4.4%)
      comprising benign fibroepithelial neoplasms with focal infarction and hybrid
      features. Half (50%) of the tumours possessed small leaf-like fronds and a
      majority had at least moderate stromal cellularity (83.8%). Most tumours had no
      discernible stromal mitoses with only 23.5% (16/68) having >=1 mitoses per 10
      high power fields. Many (79.4%) disclosed positive surgical margins. Recurrences
      occurred in 8 (11.8%) cases after excision. CONCLUSIONS: Most paediatric
      fibroepithelial tumours showed increased stromal cellularity which did not
      correlate with recurrence. Leaf-like fronds were commonly seen in paediatric
      fibroepithelial tumours apart from phyllodes tumours. Stromal mitoses were rare
      and may be a better criterion for predicting recurrence.

PMID- 25998514
TI  - Recommendations on pre-hospital and early hospital management of acute heart
      failure: a consensus paper from the Heart Failure Association of the European
      Society of Cardiology, the European Society of Emergency Medicine and the Society
      of Academic Emergency Medicine--short version.

PMID- 25998515
TI  - Incidence and predictors of cognitive impairment and dementia in Aboriginal
      Australians: A follow-up study of 5 years.
AB  - INTRODUCTION: Aboriginal Australians are reported to develop dementia earlier
      than the general population. The causes remain unknown. METHODS: This was a
      longitudinal study of 363 participants aged >=45 years. Consensus diagnoses were
      established for cognitive impairment or dementia. RESULTS: At follow-up, 189
      people (mean +/- standard deviation age, 65.4 +/- 10.3 years) participated, as
      109 (30%) had died and 65 (18%) were unavailable. The incidence of cognitive
      impairment or dementia was 52.6 (95% confidence interval 33.9, 81.5) per 1000
      person-years (380.3 total person-years) and for dementia was 21.0 (10.5, 42.1)
      per 1000 person-years (380.3 person-years total) over the age 60 years.
      Longitudinal risk factors associated with a decline from normal cognition to
      impairment were age and head injury. Other associations with cognitive decline
      were stroke, head injury, nonaspirin analgesics, lower BMI, and higher systolic
      BP. DISCUSSION: Dementia incidence in Aboriginal Australians is among the highest
      in the world, and is associated with age and head injury.

PMID- 25998516
TI  - Predictors of malignancy in pure branch duct type intraductal papillary mucinous
      neoplasm of the pancreas: A nationwide multicenter study.
AB  - BACKGROUND/OBJECTIVES: Prediction of malignancy in patients with BD-IPMNs is
      critical for the management. The aim of this study was to elucidate predictors of
      malignancy in patients with 'pure' BD-IPMNs who had a main pancreatic duct (MPD)
      diameter of <=5 mm according to the most recent international consensus criteria
      and in whom MPD involvement was excluded on postoperative histology. METHODS: We
      identified 177 patients with 'pure' BD-IPMNs based on preoperative imaging and
      postoperative histology from 15 tertiary referral centers in Korea. BD-IPMNs with
      low-grade (n = 72) and moderate-grade (n = 66) dysplasia were grouped as benign
      and BD-IPMNs with high-grade dysplasia (n = 10) and invasive carcinoma (n = 29)
      were grouped as malignancy. RESULTS: On univariate analysis, particular symptoms
      (jaundice and clinical pancreatitis), CT findings (cyst size > 3 cm, the presence
      of enhancing mural nodules) and EUS features (the presence of mural nodules, the
      mural nodule size > 5 mm) were significant risk factors predicting malignant BD
      IPMNs. Multivariate analysis revealed that the cyst size > 3 cm (odds ratio =
      9.9), the presence of enhancing mural nodules on CT (odds ratio = 19.3) and the
      mural nodule size > 5 mm on EUS (odds ratio = 14.9) were the independent risk
      factors for the presence of malignancy in BD-IPMNs (p < 0.001). CONCLUSIONS: The
      cyst size > 3 cm, the presence of enhancing mural nodules on CT, the mural nodule
      size > 5 mm on EUS are three independent predictors of malignancy in patients
      with 'pure' BD-IPMNs.

PMID- 25998517
TI  - Mechanisms of Multi-walled Carbon Nanotubes-Induced Oxidative Stress and
      Genotoxicity in Mouse Fibroblast Cells.
AB  - The extensive production and wide application of carbon nanotubes have made
      investigations of its toxic potentials necessary. In the present study, we
      explored the underlying mechanism through which multi-walled carbon nanotubes
      (MWCNTs) induce toxicity in mouse fibroblast cells (L929). 3-(4,5-Dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide and neutral red uptake viability assays
      were used to examine mechanisms of cytotoxicity. Dose and time-dependent
      cytotoxicity was observed in L929 cells. The MWCNTs significantly increased the
      generation of reactive oxygen species, lipid peroxidation, superoxide dismutase,
      and decreased glutathione. It was observed that the MWCNTs induced caspase 3
      activity. The highest DNA strand breakage was detected by comet assay at 300
      ug/mL of MWCNTs. Thus, the data indicate that MWCNTs induced cytotoxicity and
      apoptosis in L929 cells via oxidative stress. 

PMID- 25998518
TI  - The perils of meta-regression to identify clinical decision support system
      success factors.
AB  - Clinical decision support interventions are typically heterogeneous in nature,
      making it difficult to identify why some interventions succeed while others do
      not. One approach to identify factors important to the success of health
      information systems is the use of meta-regression techniques, in which potential
      explanatory factors are correlated with the outcome of interest. This approach,
      however, can result in misleading conclusions due to several issues. In this
      manuscript, we present a cautionary case study in the context of clinical
      decision support systems to illustrate the limitations of this type of analysis.
      We then discuss implications and recommendations for future work aimed at
      identifying success factors of medical informatics interventions. In particular,
      we identify the need for head-to-head trials in which the importance of system
      features is directly evaluated in a prospective manner. 

PMID- 25998519
TI  - Cancer adjuvant chemotherapy strategic classification by artificial neural
      network with gene expression data: An example for non-small cell lung cancer.
AB  - PURPOSE: Adjuvant chemotherapy (ACT) is used after surgery to prevent recurrence
      or metastases. However, ACT for non-small cell lung cancer (NSCLC) is still
      controversial. This study aimed to develop prediction models to distinguish who
      is suitable for ACT (ACT-benefit) and who should avoid ACT (ACT-futile) in NSCLC.
      METHODS: We identified the ACT correlated gene signatures and performed several
      types of ANN algorithms to construct the optimal ANN architecture for ACT benefit
      classification. Reliability was assessed by cross-data set validation. RESULTS:
      We obtained 2 probes (2 genes) with T-stage clinical data combination can get
      good prediction result. These genes included 208893_s_at (DUSP6) and 204891_s_at
      (LCK). The 10-fold cross validation classification accuracy was 65.71%. The best
      result of ANN models is MLP14-8-2 with logistic activation function. CONCLUSIONS:
      Using gene signature profiles to predict ACT benefit in NSCLC is feasible. The
      key to this analysis was identifying the pertinent genes and classification. This
      study maybe helps reduce the ineffective medical practices to avoid the waste of
      medical resources.

PMID- 25998520
TI  - Multi-faceted informatics system for digitising and streamlining the reablement
      care model.
AB  - Reablement is new paradigm to increase independence in the home amongst the
      ageing population. And it remains a challenge to design an optimal electronic
      system to streamline and integrate reablement into current healthcare
      infrastructure. Furthermore, given reablement requires collaboration with a range
      of organisations (including national healthcare institutions and
      community/voluntary service providers), such a system needs to be co-created with
      all stakeholders involved. Thus, the purpose of this study is, (1) to bring
      together stakeholder groups to elicit a comprehensive set of requirements for a
      digital reablement system, (2) to utilise emerging technologies to implement a
      system and a data model based on the requirements gathered and (3) to involve
      user groups in a usability assessment of the system. In this study we employed a
      mixed qualitative approach that included a series of stakeholder-involved
      activities. Collectively, 73 subjects were recruited to participate in an
      ideation event, a quasi-hackathon and a usability study. The study unveiled
      stakeholder-led requirements, which resulted in a novel cloud-based system that
      was created using emerging web technologies. The system is driven by a unique
      data model and includes interactive features that are necessary for streamlining
      the reablement care model. In summary, this system allows community based
      interventions (or services) to be prescribed to occupants whilst also monitoring
      the occupant's progress of independent living. 

PMID- 25998521
TI  - Intron Invasions Trace Algal Speciation and Reveal Nearly Identical Arctic and
      Antarctic Micromonas Populations.
AB  - Spliceosomal introns are a hallmark of eukaryotic genes that are hypothesized to
      play important roles in genome evolution but have poorly understood origins.
      Although most introns lack sequence homology to each other, new families of
      spliceosomal introns that are repeated hundreds of times in individual genomes
      have recently been discovered in a few organisms. The prevalence and conservation
      of these introner elements (IEs) or introner-like elements in other taxa, as well
      as their evolutionary relationships to regular spliceosomal introns, are still
      unknown. Here, we systematically investigate introns in the widespread marine
      green alga Micromonas and report new families of IEs, numerous intron presence
      absence polymorphisms, and potential intron insertion hot-spots. The new families
      enabled identification of conserved IE secondary structure features and
      establishment of a novel general model for repetitive intron proliferation across
      genomes. Despite shared secondary structure, the IE families from each Micromonas
      lineage bear no obvious sequence similarity to those in the other lineages,
      suggesting that their appearance is intimately linked with the process of
      speciation. Two of the new IE families come from an Arctic culture (Micromonas
      Clade E2) isolated from a polar region where abundance of this alga is increasing
      due to climate induced changes. The same two families were detected in
      metagenomic data from Antarctica--a system where Micromonas has never before been
      reported. Strikingly high identity between the Arctic isolate and Antarctic
      coding sequences that flank the IEs suggests connectivity between populations in
      the two polar systems that we postulate occurs through deep-sea currents.
      Recovery of Clade E2 sequences in North Atlantic Deep Waters beneath the Gulf
      Stream supports this hypothesis. Our research illuminates the dynamic
      relationships between an unusual class of repetitive introns, genome evolution,
      speciation, and global distribution of this sentinel marine alga.

PMID- 25998523
TI  - Desiccation tolerance and lichenization: a case study with the aeroterrestrial
      microalga Trebouxia sp. (Chlorophyta).
AB  - MAIN CONCLUSIONS: A comparative study of isolated vs. lichenized Trebouxia sp.
      showed that lichenization does not influence the survival capability of the alga
      to the photo-oxidative stress derived from prolonged desiccation. Coccoid algae
      in the Trebouxia genus are the most common photobionts of chlorolichens but are
      only sporadically found in soil or bark outside of a lichen. They all appear to
      be desiccation tolerant, i.e. they can survive drying to water contents of below
      10%. However, little is known about their longevity in the dry state and to which
      extent lichenization can influence it. Here, we studied the longevity in the dry
      state of the lichenized alga (LT) Trebouxia sp. in the lichen Parmotrema
      perlatum, in comparison with axenically grown cultures (CT) isolated from the
      same lichen. We report on chlorophyll fluorescence emission and reactive oxygen
      species (ROS) production before desiccation, after 15-45 days in the dry state
      under different combinations of light and air humidity and after recovery for 1
      or 3 days in fully hydrated conditions. Both the CT and the LT were able to
      withstand desiccation under high light (120 umol photons m(-2) s(-1) for 14 h per
      day), but upon recovery after 45 days in the dry state the performance of the CT
      was better than that of the LT. By contrast, the quenching of excess light energy
      was more efficient in the LT, at high relative humidities especially. ROS
      production in the LT was influenced mostly by light exposure, whereas the CT
      showed an oxidative burst independent of the light conditions. Although
      lichenization provides benefits that are essential for the survival of the
      photobiont in high-light habitats, Trebouxia sp. can withstand protracted periods
      of photo-oxidative stress even outside of a lichen thallus.

PMID- 25998522
TI  - MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric
      cancer.
AB  - MicroRNAs (miRNAs), which are small single-stranded RNA molecules composed of 18
      23 nucleotides, act as oncogenes or tumor suppressor genes playing important
      roles in tumor formation, infiltration and metastasis. Subsequently, miRNAs
      expression contributes to cancer diagnosis and prognosis. Gastric cancer
      currently has high morbidity and mortality among all malignant tumors, yet it
      lacks early specific diagnostic markers and effective treatments. In gastric
      cancer, many studies have detected abnormal expression forms of miRNAs and
      confirmed their involvement in its tumorigenesis, progression, invasion and
      metastasis. They may become valuable diagnostic markers and therapeutic targets
      for gastric cancer. Studying the role of miRNAs in gastric cancer and its
      relationship with diagnostic and prognostic parameters might help to improve the
      sensitivity of diagnosis as well as the efficacy of gastric cancer treatment.
      This review aims to highlight the advancements which might provide new methods
      for early clinical diagnosis and effective therapeutic options, along with
      predict response to treatment for gastric cancer. 

PMID- 25998524
TI  - A molecular physiological review of vegetative desiccation tolerance in the
      resurrection plant Xerophyta viscosa (Baker).
AB  - MAIN CONCLUSION: Provides a first comprehensive review of integrated
      physiological and molecular aspects of desiccation tolerance Xerophyta viscosa. A
      synopsis of biotechnological studies being undertaken to improve drought
      tolerance in maize is given. Xerophyta viscosa (Baker) is a monocotyledonous
      resurrection plant from the family Vellociacea that occurs in summer-rainfall
      areas of South Africa, Lesotho and Swaziland. It inhabits rocky terrain in
      exposed grasslands and frequently experiences periods of water deficit. Being a
      resurrection plant it tolerates the loss of 95% of total cellular water,
      regaining full metabolic competency within 3 days of rehydration. In this paper,
      we review some of the molecular and physiological adaptations that occur during
      various stages of dehydration of X. viscosa, these being functionally grouped
      into early and late responses, which might be relevant to the attainment of
      desiccation tolerance. During early drying (to 55% RWC) photosynthesis is shut
      down, there is increased presence and activity of housekeeping antioxidants and a
      redirection of metabolism to the increased formation of sucrose and raffinose
      family oligosaccharides. Other metabolic shifts suggest water replacement in
      vacuoles proposed to facilitate mechanical stabilization. Some regulatory
      processes observed include increased presence of a linker histone H1 variant, a
      Type 2C protein phosphatase, a calmodulin- and an ERD15-like protein. During the
      late stages of drying (to 10% RWC) there was increased expression of several
      proteins involved in signal transduction, and retroelements speculated to be
      instrumental in gene silencing. There was induction of antioxidants not typically
      found in desiccation-sensitive systems, classical stress-associated proteins (HSP
      and LEAs), proteins involved in structural stabilization and those associated
      with changes in various metabolite pools during drying. Metabolites accumulated
      in this stage are proposed, inter alia, to facilitate subcellular stabilization
      by vitrification process which can include glass- and ionic liquid formation.

PMID- 25998525
TI  - Deciphering UV-B-induced variation in DNA methylation pattern and its influence
      on regulation of DBR2 expression in Artemisia annua L.
AB  - MAIN CONCLUSION: UV-B-caused DNA hypomethylation and UV-B-mediated epigenetic
      activation of additional WRKY-binding site(s) in the DBR2 promoter may contribute
      to the overexpression of the DBR2 gene in Artemisia annua. DNA methylation is one
      of the key mechanisms behind stress-induced transcriptional switch off/on. Here,
      we evaluate the DNA methylation level in response to UV-B radiation in Artemisia
      annua which produces artemisinin, a sesquiterpene that has been recommended by
      WHO for the frontline treatment of malaria. However, the drug is facing serious
      shortage due to its low concentration in plants. UV-B treatment (3 h) enhanced
      artemisinin concentration up to 1.91-fold as compared to control. A key
      regulatory gene of artemisinin biosynthesis, DBR2 was upregulated under UV-B.
      This study presents observations regarding contributions of DNA methylation to
      the gene regulation using DBR2 as an example. Restriction digestion of genomic
      DNA by isoschizomers (MspI and HpaII) suggested UV-B involvement in DNA
      hypomethylation in A. annua. The global level of DNA methylation (R) was 3.4 and
      5.9% for UV-B treated and control plants, respectively, attesting hypomethylation
      of DNA in response to UV-B. Further bisulfite sequencing PCR showed demethylation
      at two CHG sites in 18S rRNA gene. Similarly, bisulfite sequencing of promoter
      region of DBR2 has demonstrated demethylation at 4 CG-, 4 CHH- and 2 CHG-sites.
      In silico analysis revealed UV-B-mediated demethylation at seven putative
      transcription factor binding sites including WRKY, which are positive regulators
      of artemisinin biosynthesis. UV-B treatment has resulted in activation of
      additional WRKY-binding site in UV-B-treated plants compared with single active
      WRKY-binding site in control and this could be the probable reason for
      overexpression of DBR2. It is suggested that DNA demethylation is an important
      epigenetic response to UV-B radiation in A. annua that surely will provide new
      horizons to further elucidate the mechanistic evidence of plant's responses to UV
      B radiation.

PMID- 25998526
TI  - Mutations and amplification of EPSPS gene confer resistance to glyphosate in
      goosegrass (Eleusine indica).
AB  - MAIN CONCLUSION: Field-evolved resistance of goosegrass to glyphosate is due to
      double or single mutation in EPSPS , or amplification of EPSPS leads to increased
      transcription and protein levels. Glyphosate has been used widely in the south of
      China. The high selection pressure from glyphosate use has led to the evolution
      of resistance to glyphosate in weeds. We investigated the molecular mechanisms of
      three recently discovered glyphosate-resistant Eleusine indica populations (R1,
      R2 and R3). The results showed that R1 and R2 had double Thr102Ile and Pro106Ser
      mutation and a single mutation of Pro106Leu in the 5-enolpyruvylshikimate-3
      phosphate synthase (EPSPS) gene, respectively. Escherichia coli containing the
      mutated EPSPS genes was tolerant to glyphosate. EPSPS activity in R1 and R2
      plants was higher than in the sensitive plants. There was no amino acid
      substitution in EPSPS gene in R3. However, expression of EPSPS in R3 plants was
      higher than in glyphosate-susceptible (S) population (13.8-fold) after glyphosate
      treatment. EPSPS enzyme activity in both R3 and S plants was inhibited by
      glyphosate, while shikimate accumulation in R3 was significantly lower than for
      the S population. Further analysis revealed that the genome of R3 contained 28.3
      fold more copies of the EPSPS gene than that of susceptible population. EPSPS
      expression was positively correlated with copy number of EPSPS. In conclusion,
      mutation of the EPSPS gene and increased EPSPS expression are part of the
      molecular mechanisms of resistance to glyphosate in Eleusine indica.

PMID- 25998527
TI  - Cloning and functional characterization of two monoterpene acetyltransferases
      from glandular trichomes of L. x intermedia.
AB  - MAIN CONCLUSION: Two alcohol acetyltransferases, LiAAT-3 and LiAAT-4, from L. x
      intermedia were cloned, expressed in bacteria, and functionally characterized.
      Two monoterpene acetyltransferase cDNA clones (LiAAT-3 and LiAAT-4) were isolated
      from L. x intermedia glandular trichomes, expressed in bacteria to produce, and
      functionally characterize the encoded proteins in vitro. The recombinant LiAAT-3
      and LiAAT-4 proteins had molecular weights of ca. 47 and 49 kDa, respectively, as
      evidenced by SDS-PAGE. The K m (mM) values for the recombinant LiAAT-3 and LiAAT
      4 were 1.046 and 0.354 for lavandulol, 1.31 and 0.279 for geraniol, and 0.87 and
      0.113 for nerol, respectively. The V max (pkat/mg) values for LiAAT-3 and LiAAT-4
      were 92.13 and 105.1 for lavandulol, 81.07 and 52.17 for geraniol, and 15.02 and
      15.8 for nerol, correspondingly. Catalytic efficiencies (mM(-1) min(-1)) for
      LiAAT-3 and LiAAT-4 were 0.27 and 0.85 for lavandulol, 0.19 and 0.54 for
      geraniol, and 0.052 and 0.4 for nerol, respectively. These kinetic properties are
      in the range of those reported for other plant acetyltransferases, and indicate
      that LiAAT-4 has a better catalytic efficiency than LiAAT-3, with lavandulol
      serving as the preferred substrate for both enzymes. Transcripts for both genes
      were abundant in L. angustifolia and L. x intermedia flowers, where monoterpene
      acetates are produced, and were undetectable (or present in trace quantities) in
      L. latifolia flowers, which do not accumulate significant amounts of these
      metabolites.

PMID- 25998528
TI  - Brassinosteroid is required for sugar promotion of hypocotyl elongation in
      Arabidopsis in darkness.
AB  - MAIN CONCLUSION: Brassinosteroid is necessary for sugar promotion of Arabidopsis
      hypocotyl elongation in darkness, and sugar positively regulates BRASSINAZOLE
      RESISTANT1 (BZR1) at both transcription and protein levels. Sugar has the ability
      to induce Arabidopsis hypocotyl elongation in the dark, but the detailed
      mechanisms remain not well understood. Here, we report that the steroidal
      phytohormone brassinosteroid (BR) is involved in sugar promotion of hypocotyl
      elongation in the dark. Sugar-induced hypocotyl elongation was significantly
      repressed in the BR-deficient mutant det2-1, BR-insensitive mutant bri1-5, and
      wild-type plants (Col-0), but not in the BR-hypersensitive mutants bzr1-1D and
      bes1-D treated with the BR biosynthetic inhibitor brassinazole (BRZ). Sugar also
      up-regulated the expression of genes that are related to cell elongation in a BR
      dependent manner, and this effect was more remarkable in bzr1-1D and bes1-D than
      in their corresponding wild types in the presence of BRZ, suggesting an important
      role of BZR1 and bri1-ems-suppressor 1 (BES1) in this process. Sugar treatment
      seems to have little effect on BR biosynthesis, but enhances the expression of
      BZR1 and BES1, two transcription factors in BR signaling, in the dark.
      Furthermore, sugar treatment maintains higher BZR1 protein levels in plants grown
      in the dark. Collectively, our results indicate that BR is required for sugar
      promotion of hypocotyl elongation in darkness in Arabidopsis.

PMID- 25998529
TI  - A class III chitinase without disulfide bonds from the fern, Pteris ryukyuensis:
      crystal structure and ligand-binding studies.
AB  - MAIN CONCLUSION: We first solved the crystal structure of class III catalytic
      domain of a chitinase from fern (PrChiA-cat), and found a structural difference
      between PrChiA-cat and hevamine. PrChiA-cat was found to have reduced affinities
      to chitin oligosaccharides and allosamidin. Plant class III chitinases are
      subdivided into enzymes with three disulfide bonds and those without disulfide
      bonds. We here referred to the former enzymes as class IIIa chitinases and the
      latter as class IIIb chitinases. In this study, we solved the crystal structure
      of the class IIIb catalytic domain of a chitinase from the fern Pteris
      ryukyuensis (PrChiA-cat), and compared it with that of hevamine, a class IIIa
      chitinase from Hevea brasiliensis. PrChiA-cat was found to adopt an (alpha/beta)8
      fold typical of GH18 chitinases in a similar manner to that of hevamine. However,
      PrChiA-cat also had two large loops that extruded from the catalytic site, and
      the corresponding loops in hevamine were markedly smaller than those of PrChiA
      cat. An HPLC analysis of the enzymatic products revealed that the mode of action
      of PrChiA-cat toward chitin oligosaccharides, (GlcNAc) n (n = 4-6), differed from
      those of hevamine and the other class IIIa chitinases. The binding affinities of
      (GlcNAc)3 and (GlcNAc)4 toward the inactive mutant of PrChiA-cat were determined
      by isothermal titration calorimetry, and were markedly lower than those toward
      other members of the GH18 family. The affinity and the inhibitory activity of
      allosamidin toward PrChiA-cat were also lower than those toward the GH18
      chitinases investigated to date. Several hydrogen bonds found in the crystal
      structure of hevamine-allosamidin complex were missing in the modeled structure
      of PrChiA-cat-allosamidin complex. The structural findings for PrChiA-cat
      successfully interpreted the functional data presented.

PMID- 25998532
TI  - Two-dimensional graphene-like C2N: an experimentally available porous membrane
      for hydrogen purification.
AB  - We theoretically demonstrate that the two-dimensional porous C2N sheet exhibits
      an extremely high selectivity and large permeance in favour of H2 among other
      atmospheric gases. This experimentally available porous C2N is superior to
      traditional membranes, such as polymers and silica, and could have great
      potential for hydrogen separation. 

PMID- 25998530
TI  - Rejection triggers liver transplant tolerance: Involvement of mesenchyme-mediated
      immune control mechanisms in mice.
AB  - Liver tolerance was initially recognized by the spontaneous acceptance of liver
      allografts in many species. The underlying mechanisms are not completely
      understood. However, liver transplant (LT) tolerance absolutely requires
      interferon (IFN)-gamma, a rejection-associated inflammatory cytokine. In this
      study, we investigated the rejection of liver allografts deficient in the IFN
      gamma receptor and reveal that the liver graft is equipped with machineries
      capable of counterattacking the host immune response through a mesenchyme
      mediated immune control (MMIC) mechanism. MMIC is triggered by T effector (Tef)
      cell-derived IFN-gamma that drives expression of B7-H1 on graft mesenchymal cells
      leading to Tef cell apoptosis. We describe the negative feedback loop between
      graft mesenchymal and Tef cells that ultimately results in LT tolerance.
      Comparable elevations of T-regulatory cells and myeloid-derived suppressor cells
      were observed in both rejection and tolerance groups and were not dependent on
      IFN-gamma stimulation, suggesting a critical role of Tef cell elimination in
      tolerance induction. We identify potent MMIC activity in hepatic stellate cells
      and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver,
      given that spontaneous acceptance of kidney allografts has been reported,
      although less commonly, probably reflecting variance in MMIC activity.
      CONCLUSION: MMIC may represent an important homeostatic mechanism that supports
      peripheral tolerance and could be a target for the prevention and treatment of
      transplant rejection. This study highlights that the graft is an active
      participant in the equipoise between tolerance and rejection and warrants more
      attention in the search for tolerance biomarkers.

PMID- 25998531
TI  - Etiology of Femoroacetabular Impingement in Athletes: A Review of Recent
      Findings.
AB  - The relationship between hip deformities and osteoarthritis has recently received
      a lot of attention. In particular, it has been shown that both osteoarthritis and
      its precursors, such as the hip deformities that lead to femoroacetabular
      impingement (FAI), are more prevalent in elite athletes compared with the general
      population. However, the etiology of the above-mentioned types of hip deformity
      is not currently well understood. Many recent studies have attempted to shed
      light on the etiology of this disease. In this article, the main clinical,
      radiological, mechanobiological, and biomechanical findings of relevance to
      understanding the etiology of hip deformities leading to FAI are reviewed. Based
      on these findings, a consistent biomechanical theory explaining the development
      of hip deformities in athletes is then presented. According to the presented
      theory, the repetitive, impact-like musculoskeletal loads that athletes
      experience, particularly when they undertake extreme ranges of hip motion, cause
      the development of hip deformities. According to this theory, these
      musculoskeletal loads trigger abnormal growth patterns during the years of
      skeletal development and cause the formation of hip deformities. A number of
      hypotheses based on the proposed theory are then formulated that could be tested
      in future studies to ascertain whether the proposed theory could sufficiently
      describe the development of hip deformities in athletes. 

PMID- 25998533
TI  - A Simple Technique for Bone Storage after Decompressive Craniectomy in Children.
AB  - Cranial vault reconstruction in the pediatric population is a specialized
      procedure, which requires additional considerations. Generally, inherent
      difficulties of bone storage and cranioplasty are neglected in the literature. We
      present a simple method of bone storage and autologous cranioplasty in a small
      child with severe head injury. The child underwent surgical treatment with
      decompressive craniectomy. A bone flap was transversally divided into two pieces
      and stored under the galea. Bone storage and reconstruction of the cranial vault
      with our surgical technique is a safe, easy and cost-effective choice excluding
      the surgical trauma to obtain a new subcutanous pocket for bone storage in
      pediatric decompressive craniectomy patients.

PMID- 25998534
TI  - Transradial Sheathless Approach for PCI.
AB  - The lumen of the radial artery in many patients is smaller than the outer
      diameter of a 6F radial sheath frequently leading to procedural pain, trauma to
      the radial artery and contributing to radial occlusion. Chronically, neointima
      formation reduces luminal size further, limiting successful re-intervention in
      some patients. Sheathless guides are 1-2F sizes smaller than corresponding
      sheaths and so may potentially reduce radial artery trauma. Although not
      currently recommended for routine use, the 6.5F Asahi EauCath Sheathless guide
      has a lower profile than a 5F sheath and the same inner lumen as a 6F guide and
      has been shown to be especially useful for interventional procedures requiring 6F
      techniques in patients with small radial arteries. Similarly, the 7.5F Asahi
      EauCath has a lower profile than a 6F sheath and the same inner lumen as a 7F
      guide and is useful for procedures requiring a large bore guide catheter.
      Alternatives include the MediKit Works 5F sheathless system and long dilators
      designed to allow the sheathless introduction of conventional guides. The
      recently approved 'Flip' dilator is now available outside Japan; however,
      experience is currently limited.

PMID- 25998536
TI  - Testing the Effect of Refrigerated Storage on Testate Amoeba Samples.
AB  - Samples for analysis of testate amoebae and other protists frequently need to be
      stored for many months before microscopy. This storage commonly involves
      refrigeration, but we know that testate amoebae can live and reproduce in these
      conditions. This raises the question: do communities change during storage and
      how might this effect the data produced? We analysed Sphagnum samples over a 16
      week period to address this question. Our results show no evidence for detectable
      change. This is a reassuring result supporting much current practice although we
      suggest that frozen storage or the addition of a fixative may be worthwhile
      precautions where feasible. 

PMID- 25998535
TI  - How do we estimate survival? External validation of a tool for survival
      estimation in patients with metastatic bone disease-decision analysis and
      comparison of three international patient populations.
AB  - BACKGROUND: We recently developed a clinical decision support tool, capable of
      estimating the likelihood of survival at 3 and 12 months following surgery for
      patients with operable skeletal metastases. After making it publicly available on
      www.PATHFx.org , we attempted to externally validate it using independent,
      international data. METHODS: We collected data from patients treated at 13
      Italian orthopaedic oncology referral centers between 2010 and 2013, then applied
      to PATHFx, which generated a probability of survival at three and 12-months for
      each patient. We assessed accuracy using the area under the receiver-operating
      characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA),
      and compared the Italian patient data to the training set (United States) and
      first external validation set (Scandinavia). RESULTS: The Italian dataset
      contained 287 records with at least 12 months follow-up information. The AUCs for
      the three-month and 12-month estimates was 0.80 and 0.77, respectively. There
      were missing data, including the surgeon's estimate of survival that was missing
      in the majority of records. Physiologically, Italian patients were similar to
      patients in the training and first validation sets. However notable differences
      were observed in the proportion of those surviving three and 12-months,
      suggesting differences in referral patterns and perhaps indications for surgery.
      CONCLUSIONS: PATHFx was successfully validated in an Italian dataset containing
      missing data. This study demonstrates its broad applicability to European
      patients, even in centers with differing treatment philosophies from those
      previously studied.

PMID- 25998537
TI  - Sepsis-induced brain mitochondrial dysfunction is associated with altered
      mitochondrial Src and PTP1B levels.
AB  - Sepsis-induced brain dysfunction (SIBD) is often the first manifestation of
      sepsis, and its pathogenesis is associated with mitochondrial dysfunction. In
      this study, we investigated the roles of the tyrosine kinase Src and protein
      tyrosine phosphatase 1B (PTP1B) in brain mitochondrial dysfunction using a rat
      model of lipopolysaccharide (LPS)-induced sepsis. We found that there was a
      gradual and significant increase of PTP1B levels in the rat brain after sepsis
      induction. In contrast, brain Src levels were reduced in parallel with the PTP1B
      increase. Sepsis led to significantly reduced tyrosine phosphorylation of
      mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III.
      Pretreatment of mitochondrial proteins with active PTP1B significantly inhibited
      complexes I and III activities in vitro, whereas Src enhanced complexes I, II,
      and III activities. PTP1B and Src were each co-immunoprecipitated with OXPHOS
      complexes I and III, suggesting direct interactions between both proteins and
      complexes I and III. Src also directly interacted with complex II. Furthermore,
      pretreatment of mitochondrial proteins with active PTP1B resulted in
      overproduction of reactive oxygen species and decreased mitochondrial membrane
      potential. Pretreatment with active Src produced the opposite effect. These
      results suggest that brain mitochondrial dysfunction following LPS-induced sepsis
      in rats is partly attributed to PTP1B and Src mediated decrease in mitochondrial
      protein tyrosine phosphorylation. 

PMID- 25998538
TI  - Extracellular alpha-crystallin protects astrocytes from cell death through
      activation of MAPK, PI3K/Akt signaling pathway and blockade of ROS release from
      mitochondria.
AB  - alpha-Crystallin with two isoforms, alphaA-crystallin (HSPB4) and alphaB
      crystallin (HSPB5), is found in eye lens, spleen, lung, kidney, cornea, skin, but
      also in brain. Several studies revealed roles of alphaA/alphaB-crystallin in
      regulating cell viability and protection in the central nervous system. We
      previously demonstrated that alpha-crystallin serves as an intracellular
      protectant in astrocytes. Compared to well-studied intracellular functions of
      alpha-crystallin, there is limited proof for the role of alpha-crystallin as
      extracellular protectant. In order to clarify protective effects of extracellular
      alphaA/alphaB-crystallin, we exposed astrocytes to the toxic agents,
      staurosporine or C2-ceramide, or serum-starvation in the presence of
      alphaA/alphaB-crystallin. Extracellular alphaA/alphaB-crystallin protected
      astrocytes from staurosporine- and C2-ceramide-induced cell death. In addition,
      extracellular alphaB-crystallin/HSPB5 effectively promoted astrocytes viability
      through phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian
      target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2
      (ERK1/2), p38 mitogen-activated protein kinases (p38) and c-Jun N-terminal
      kinases (JNK) signaling pathways under serum-deprivation. Furthermore, alphaB
      crystallin/HSPB5 decreases the staurosporine-mediated cleavage of caspase 3
      through PI3K/Akt signaling preventing apoptosis of astrocytes. Thus, the current
      study indicates that extracellular alphaA/alphaB-crystallin protects astrocytes
      exposed to various harmful stimuli. Furthermore, application of alphaB
      crystallin/HSPB5 to isolated rat brain mitochondria inhibits ROS generation
      induced by complex III inhibition with Antimycin A. 

PMID- 25998539
TI  - The neurobiological drive for overeating implicated in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly
      by hyperphagia and early childhood obesity. Previous fMRI studies examined the
      activation of eating-related neural circuits in PWS patients with or without
      exposures to food cues and found an excessive eating motivation and a reduced
      inhibitory control of cognitive processing of food. However, the effective
      connectivity between various brain areas or neural circuitry critically
      implicated in both the biological and behavioral control of overeating in PWS is
      largely unexplored. The current study combined resting-state fMRI and Granger
      causality analysis (GCA) techniques to investigate interactive causal influences
      among key neural pathways underlying overeating in PWS. We first defined the
      regions of interest (ROIs) that demonstrated significant alterations of the
      baseline brain activity levels in children with PWS (n = 21) as compared to that
      of their normal siblings controls (n = 18), and then carried out GCA to
      characterize the region-to-region interactions among these ROIs. Our data
      revealed significantly enhanced causal influences from the amygdala to the
      hypothalamus and from both the medial prefrontal cortex and anterior cingulate
      cortex to the amygdala in patients with PWS (P < 0.001). These alterations offer
      new explanations for hypothalamic regulation of homeostatic energy intake and
      impairment in inhibitory control circuit. The deficits in these dual aspects may
      jointly contribute to the extreme hyperphagia in PWS. This study provides both a
      new methodological and a neurobiological perspective to aid in a better
      understanding of neural mechanisms underlying obesity in the general public. This
      article is part of a Special Issue entitled 1618.

PMID- 25998540
TI  - Alterations to the attention system in adults with tinnitus are modality
      specific.
AB  - Generation and persistence of tinnitus following hearing loss may be due to
      aberrant engagement of attention. Here, functional MRI was used to determine
      differences in auditory and visual attention processing in adults with tinnitus
      and hearing loss compared to two age-matched control groups, one with matched
      hearing loss and the other with normal hearing thresholds. Attentional processing
      was investigated using a short-term memory task with varying loads, employing
      unfamiliar Korean letters in the visual condition and non-speech sounds in the
      auditory condition. We found similar behavioral response across the three groups
      for both modalities and tasks. For the auditory modality, the response of the
      attention network was suppressed in the tinnitus group compared to the control
      groups for both task loads, with the effect being more pronounced at high load.
      In contrast, in the visual modality, the tinnitus group exhibited greater
      response of the attention network, regardless of memory load, compared to the
      control groups. The results increase our understanding of the neural mechanisms
      of tinnitus and suggest that interventions that manipulate attention, especially
      in the visual domain, should be further investigated. 

PMID- 25998541
TI  - Activity in the brain network for dynamic manipulation of unstable objects is
      robust to acute tactile nerve block: An fMRI study.
AB  - OBJECTIVE: To study whether a temporary block of the tactile afferents from the
      fingers causes altered activity in the neural network for dexterous manipulation.
      METHODS: Whole-brain functional Magnetic Resonance Imaging (fMRI) was conducted
      in 18 healthy subjects, while they compressed an unstable spring between the
      thumb and index finger of the right hand. Two sensory conditions--with and
      without tactile input from the fingers--were employed. In the latter condition
      the digital nerves were blocked by local anesthesia. RESULTS: Compression of the
      unstable spring was associated with activity in an earlier described network for
      object manipulation. We found that this entire network remained active after a
      nerve block, and the activity was increased in the dorsal premotor cortex.
      CONCLUSIONS: The neural network for dexterous manipulation is robust with only
      minor alterations after acute loss of tactile information from the fingers. There
      was no loss of activity, but, unexpectedly, an increased activity in some parts
      of the network. SIGNIFICANCE: This study gives new insights to possible neural
      compensatory mechanisms that make fine motor control possible after acute
      disruption of tactile information in natural situations like cold weather or
      wearing surgical gloves.

PMID- 25998542
TI  - Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in
      the cortex and globus pallidus of freely moving rats.
AB  - Abnormal oscillation in the cortical-basal ganglia loop is involved in the
      pathophysiology of parkinsonism. High-voltage spindles (HVSs), one of the main
      type abnormal oscillations in Parkinson's disease, are regulated by dopamine D2
      like receptors but not D1-like receptors. However, little is known about how
      dopamine D2-like receptors regulate HVSs and the role of hyperpolarization
      activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation. We simultaneously
      recorded the local field potential (LFP) in globus pallidus (GP) and
      electrocorticogram (ECoG) in primary motor cortex (M1) in freely moving 6
      hydroxydopamine (6-OHDA) lesioned or control rats. The expression of HCN2 and
      dopamine D2 receptor in the subthalamic nucleus (STN) was examined by
      immunochemical staining and Western blotting. We also tested the role of HCN2 in
      HVSs regulation by using pharmacological and shRNA methodology. We found that
      dopamine D2-like receptor agonists suppressed the increased HVSs in 6-OHDA
      lesioned rats. HCN2 was co-expressed with dopamine D2 receptor in the STN, and
      dopamine depletion decreased the expression of HCN2 as well as dopamine D2
      receptor which contribute to the regulation of HVSs. HCN2 was down regulated by
      HCN2 shRNA, which thereby led to an increase in the HVSs in naive rats while HCN2
      agonist reduced the HVSs in 6-OHDA lesioned rats. These results suggest that HCN2
      in the STN is involved in abnormal oscillation regulation between M1 cortex and
      GP.

PMID- 25998543
TI  - Experimental evidence that bioenergetics disruption is not mainly involved in the
      brain injury of glutaryl-CoA dehydrogenase deficient mice submitted to lysine
      overload.
AB  - Bioenergetics dysfunction has been postulated as an important pathomechanism of
      brain damage in glutaric aciduria type I, but this is still under debate. We
      investigated activities of citric acid cycle (CAC) enzymes, lactate release,
      respiration and membrane potential (DeltaPsim) in mitochondrial preparations from
      cerebral cortex and striatum of 30-day-old glutaryl-CoA dehydrogenase deficient
      (Gcdh-/-) and wild type mice fed a baseline or a high lysine (Lys, 4.7%) chow for
      60 or 96h. Brain histological analyses were performed in these animals, as well
      as in 90-day-old animals fed a baseline or a high Lys chow during 30 days
      starting at 60-day-old. A moderate reduction of citrate synthase and isocitrate
      dehydrogenase activities was observed only in the striatum from 30-day-old Gcdh-/
      animals submitted to a high Lys chow. In contrast, the other CAC enzyme
      activities, lactate release, the respiratory parameters state 3, state 4, the
      respiratory control ratio and CCCP-stimulated (uncoupled) state, as well as
      DeltaPsim were not altered in the striatum. Similarly, none of the evaluated
      parameters were changed in the cerebral cortex from these animals under baseline
      or Lys overload. On the other hand, histological analyses revealed the presence
      of intense vacuolation in the cerebral cortex of 60 and 90-day-old Gcdh-/- mice
      fed a baseline chow and in the striatum of 90-day-old Gcdh-/- mice submitted to
      Lys overload for 30 days. Taken together, the present data demonstrate mild
      impairment of bioenergetics homeostasis and marked histological alterations in
      striatum from Gcdh-/- mice under a high Lys chow, suggesting that disruption of
      energy metabolism is not mainly involved in the brain injury of these animals. 

PMID- 25998544
TI  - The use of morselized allografts without impaction and cemented cage support in
      acetabular revision surgery: a 4- to 9-year follow-up.
AB  - BACKGROUND: Acetabular revision arthroplasty with major bone loss is one of the
      most difficult operations in orthopedic surgery. The goal of the study was to
      evaluate midterm clinical results of the use of morselized allografts with
      cemented cage support in revision total hip replacement. METHODS: We identified
      28 patients (29 hips) at an average follow-up of 73 months. Harris Hip Scores
      (HHS) were assessed before and after surgery. Pre- and postoperative radiographs
      were evaluated for restoration of the center of rotation, component migration,
      and graft incorporation. RESULTS AND DISCUSSION: At follow-up, the mean HHS
      improved from 34 (range, 20-45) to 80 (range, 71-98) points. None of the
      components had been re-revised. On average, the revised hip center of rotation
      was improved significantly. Incorporation of the graft was complete in 23 hips.
      The midterm result of cage reconstruction with morselized bone allograft is
      relatively better than other studies using a similar cage construction. We
      believe we have three special modifications of this reconstruction technique that
      are beneficial for bone incorporation. CONCLUSIONS: These data confirm that
      acetabular reconstruction using morselized allografts and cemented acetabular
      cages is effective in the midterm as a treatment for acetabular loosening with
      massive bone deficiency.

PMID- 25998545
TI  - Cross-cultural adaptation, reliability and validity of the Turkish version of the
      Upper Limb Functional Index (ULFI).
AB  - STUDY DESIGN: Clinical measurement. BACKGROUND: The Upper Limb Functional Index
      (ULFI) is a patient reported outcome (PRO) measure with sound clinimetric
      properties and clinical viability for determination of upper limb function.
      PURPOSE-METHODS: The aims of this study were to cross-culturally adapt the ULFI
      for Turkish-speaking patients (ULFI-Tk) and investigate the reliability and
      validity in patients with upper limb problems. Patients (n=l02, age 49.1+/-16.6)
      with upper limb disorders were consecutively recruited. All participants
      completed the ULFI-Tk and the Disability of Arm, Shoulder and Hand Turkish
      version (DASH-Tk) criterion at baseline and day-three. RESULTS: The ULFI-Tk
      demonstrated good internal consistency (alpha=0.87), moderate criterion validity
      (DASH-Tk:r=0.68;p<0.05), moderate reliability (ICC2:1=0.72,CI=0.58-0.80) and
      strong error measurement (SEM=2.94;MDC90=5.35). Exploratory factor analysis
      demonstrated a dual factor structure that explained 31.2% of total variance.
      CONCLUSIONS: The ULFI-Tk is a reliable and valid PRO that could be used to assess
      upper limb musculoskeletal disorders in Turkish speaking patients LEVEL OF
      EVIDENCE: Class 2.

PMID- 25998546
TI  - Factors affecting functional recovery after surgery and hand therapy in patients
      with Dupuytren's disease.
AB  - STUDY DESIGN: Prospective cohort study. INTRODUCTION: The evidence of the
      relationship between functional recovery and impairment after surgery and hand
      therapy are inconsistent. PURPOSE OF THE STUDY: To explore factors that were most
      related to functional recovery as measured by DASH in patients with Dupuytren's
      disease. METHODS: Eighty-one patients undergoing surgery and hand therapy were
      consecutively recruited. Functional recovery was measured by the Disability of
      the Arm, Shoulder and Hand (DASH) questionnaire. Explanatory variables: range of
      motion of the finger joints, five questions regarding safety and social issues of
      hand function, and health-related quality of life (Euroqol). RESULTS: The three
      variables "need to take special precautions", "avoid using the hand in social
      context", and health-related quality of life (EQ-5D index) explained 62.1% of the
      variance in DASH, where the first variable had the greatest relative effect.
      DISCUSSION: Safety and social issues of hand function and quality of life had an
      evident association with functional recovery. LEVEL OF EVIDENCE: IV.

PMID- 25998547
TI  - Programmes, policies and implementation.

PMID- 25998548
TI  - Optimizing child-focused nutrition policies: considerations and controversies.

PMID- 25998549
TI  - Trayless cafeterias lead diners to take less salad and relatively more dessert.
AB  - OBJECTIVE: Many colleges are removing trays from their dining facilities in hope
      of reducing waste. How does not having a tray impact food choice? DESIGN: A field
      study was conducted in a university cafeteria (n 417) on two evenings with
      identical menus, one with tray service and one without. SETTING: A dining hall of
      a large north-eastern university, USA. SUBJECTS: Undergraduate students. RESULTS:
      Trayless dining decreased the percentage of diners (average age 19.1 years) who
      took salad by 65.2% but did not decrease the percentage who took dessert, leading
      to a markedly higher ratio of dessert to salad. CONCLUSIONS: Cafeterias going
      trayless should consider complementary policies to encourage balanced diets.

PMID- 25998550
TI  - Beyond the randomised controlled trial and BMI--evaluation of effectiveness of
      through-school nutrition and physical activity programmes.

PMID- 25998551
TI  - Socio-cultural influences on the behaviour of South Asian women with diabetes in
      pregnancy: qualitative study using a multi-level theoretical approach.
AB  - BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those
      from low-income backgrounds, and leads to short-term morbidity and longer-term
      metabolic programming in mother and offspring. We sought to understand the
      multiple influences on behaviour (hence risks to metabolic health) of South Asian
      mothers and their unborn child, theorise how these influences interact and build
      over time, and inform the design of culturally congruent, multi-level
      interventions. METHODS: Our sample for this qualitative study was 45 women of
      Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a
      history of diabetes in pregnancy, recruited from diabetes and antenatal services
      in two deprived London boroughs. Overall, 17 women shared their experiences of
      diabetes, pregnancy, and health services in group discussions and 28 women gave
      individual narrative interviews, facilitated by multilingual researchers,
      audiotaped, translated, and transcribed. Data were analysed using the constant
      comparative method, drawing on sociological and narrative theories. RESULTS: Key
      storylines (over-arching narratives) recurred across all ethnic groups studied.
      Short-term storylines depicted the experience of diabetic pregnancy as stressful,
      difficult to control, and associated with negative symptoms, especially
      tiredness. Taking exercise and restricting diet often worsened these symptoms and
      conflicted with advice from relatives and peers. Many women believed that
      exercise in pregnancy would damage the fetus and drain the mother's strength, and
      that eating would be strength-giving for mother and fetus. These short-term
      storylines were nested within medium-term storylines about family life,
      especially the cultural, practical, and material constraints of the traditional
      South Asian wife and mother role and past experiences of illness and healthcare,
      and within longer-term storylines about genetic, cultural, and material heritage 
      including migration, acculturation, and family memories of food insecurity.
      While peer advice was familiar, meaningful, and morally resonant, health
      education advice from clinicians was usually unfamiliar and devoid of cultural
      meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and
      managing diabetes in South Asian women before and during pregnancy are likely to
      be ineffective if delivered in a socio-cultural vacuum. Individual education
      should be supplemented with community-level interventions to address the socio
      material constraints and cultural frames within which behavioural 'choices' are
      made.

PMID- 25998552
TI  - Recombinant hIFN-alpha2b-BCG inhibits tumor growth in a mouse model of bladder
      cancer.
AB  - Bacillus Calmette-Guerin (BCG) reduces the recurrence and progression of non
      muscle invasive bladder cancer. The present study aimed to investigate the impact
      of a recombinant hIFN-alpha2b-secreting BCG (rBCG) on the mouse bladder MB49 cell
      line and an orthotopic mouse model of bladder cancer. MB49 cells were cultivated
      in the presence or absence of rBCG, BCG or BCG+hIFN-alpha2b. Cellular morphology
      and viability were assessed by microscopy and CCK-8 assay, respectively.
      Apoptosis was assessed by acridine orange, Hoechst 33258 staining and flow
      cytometry. MHC-I expression was assessed by flow cytometry. MB49 cells were
      transplanted into the bladders of C57BL/6 mice administered BCG, rBCG or BCG+hIFN
      alpha2b. Local tissue Fas expression and T cell subsets were assessed by
      immunohistochemistry. Peripheral blood TNF-alpha and IL-12 levels were measured
      by ELISA, and circulating T lymphocyte subsets by flow cytometry. BCG, rBCG and
      BCG+hIFN-alpha2b increased the distortion and death of MB49 cells, yet rBCG
      reduced the proliferation and enhanced apoptosis most substantially. Apoptosis
      was increased after a 24-h co-culture with rBCG or BCG+hIFN-alpha2b. Mice
      administered rBCG survived longer than mice administered BCG (p<0.001), yet this
      result was not significantly different from mice administered BCG+hIFN-alpha2b.
      The average bladder weight was reduced by administration of rBCG (p<0.001). Fas
      expression and peripheral blood mTNF-alpha and mIL-12, cell counts of
      polymorphonuclear leukocytes, monocytes, T lymphocytes and CD4+/CD8+ ratios were
      significantly increased by all BCG treatments (p<=0.05), yet monocyte and T
      lymphocyte counts were higher in mice administered rBCG than in mice treated with
      BCG or BCG+hIFN-alpha2b (p=0.000). These results indicate that in an orthotopic
      murine bladder cancer model rBCG possesses superior antitumor activity to
      BCG+hIFN-alpha2b.

PMID- 25998553
TI  - CTLA4 and CD28 Gene Polymorphisms with Respect to Affective Symptom Domain in
      Schizophrenia.
AB  - BACKGROUND: Accumulating evidence indicates that immune alterations in
      schizophrenia are due to genetic underpinnings. Here, we aimed at investigating
      whether polymorphisms in CTLA4 and CD28 genes, encoding molecules that regulate T
      cell activity, influence schizophrenia symptomatology. METHOD: We recruited 120
      schizophrenia patients and 380 healthy age- and sex-matched controls. We divided
      the patients into two groups: one with no co-occurrence between psychotic and
      affective symptoms and the second one with psychotic symptoms dominating in the
      clinical manifestation, although also with occasional affective disturbances in
      the course of illness. RESULTS: Among the patients with co-occurring affective
      symptoms, there were significantly more CTLA4 c.49A>G[A] alleles (p = 0.018, odds
      ratio (OR) 2.03, 95% confidence interval (CI) 1.2-3.66) and more CTLA4
      g.319C>T[T] alleles (p = 0.07, OR 1.93, 95% CI 0.94-4.13) in comparison to the
      second group. Additionally, we have shown that CD28 c.17 + 3T>C[C+] were more
      significantly overrepresented among patients with co-occurring psychotic and
      affective symptoms (p = 0.0003, OR 3.36, 95% CI 1.69-6.68) than in patients
      without co-occurence between these symptoms (p = 0.012, OR 1.88, 95% CI 1.15
      3.10). CONCLUSION: CTLA4 and CD28 gene polymorphisms may not only act in immune
      deregulation observed in schizophrenia, but may also influence the course of the
      illness by modifying the susceptibility to the co-occurrence of psychotic and
      affective symptoms.

PMID- 25998554
TI  - Molecular interactions of the Saccharomyces cerevisiae Atg1 complex provide
      insights into assembly and regulatory mechanisms.
AB  - The Atg1 complex, which contains 5 major subunits: Atg1, Atg13, Atg17, Atg29, and
      Atg31, regulates the induction of autophagy and autophagosome formation. To gain
      a better understanding of the overall architecture and assembly mechanism of this
      essential autophagy regulatory complex, we have reconstituted a core assembly of
      the Saccharomyces cerevisiae Atg1 complex composed of full-length Atg17, Atg29,
      and Atg31, along with the C-terminal domains of Atg1 (Atg1[CTD]) and Atg13
      (Atg13[CTD]). Using chemical-crosslinking coupled with mass spectrometry (CXMS)
      analysis we systematically mapped the intersubunit interaction interfaces within
      this complex. Our data revealed that the intrinsically unstructured C-terminal
      domain of Atg29 interacts directly with Atg17, whereas Atg17 interacts with Atg13
      in 2 distinct intrinsically unstructured regions, including a previously unknown
      motif that encompasses several putative phosphorylation sites. The Atg1[CTD]
      crosslinks exclusively to the Atg13[CTD] and does not appear to make direct
      contact with the Atg17-Atg31-Atg29 scaffold. Finally, single-particle electron
      microscopy analysis revealed that both the Atg13[CTD] and Atg1[CTD] localize to
      the tip regions of Atg17-Atg31-Atg29 and do not alter the distinct curvature of
      this scaffolding subcomplex. This work provides a comprehensive understanding of
      the subunit interactions in the fully assembled Atg1 core complex, and uncovers
      the potential role of intrinsically disordered regions in regulating complex
      integrity. 

PMID- 25998555
TI  - Pyrrole-imidazole polyamide-mediated silencing of KCNQ1OT1 expression induces
      cell death in Wilms' tumor cells.
AB  - KvDMR (an intronic CpG island within the KCNQ1 gene) is one of the imprinting
      control regions on human chromosome 11p15.5. Since KvDMR exists within the
      promoter region of KCNQ1OT1 (antisense transcript of KCNQ1), it is likely that
      genomic alterations of this region including deletion, paternal uniparental
      disomy and de-methylation in maternal allele lead to aberrant overexpression of
      KCNQ1OT1. Indeed, de-methylation of KvDMR accompanied by uncontrolled
      overexpression of KCNQ1OT1 occurs frequently in Beckwith-Wiedemann syndrome
      (BWS), and around 10% of BWS patients developed embryonal tumors (Wilms' tumor or
      hepatoblastoma). These observations strongly suggest that silencing of KCNQ1OT1
      expression might suppress its oncogenic potential. In the present study, we
      designed two pyrrole-imidazole (PI) polyamides, termed PI-a and PI-b, which might
      have the ability to bind to CCAAT boxes of the KCNQ1OT1 promoter region, and
      investigated their possible antitumor effect on Wilms' tumor-derived G401 cells.
      Gel retardation assay demonstrated that PI-a and PI-b specifically bind to their
      target sequences. Microscopic observations showed the efficient nuclear access of
      these PI polyamides. Quantitative real-time PCR analysis revealed that the
      expression level of KCNQ1OT1 was significantly decreased when treated with PI-a
      and PI-b simultaneously but not with either PI-a or PI-b single treatment.
      Consistent with these results, the combination of PI-a and PI-b resulted in a
      significant reduction in viability of G401 cells in a dose-dependent manner.
      Furthermore, FACS analysis demonstrated that combinatory treatment with PI-a and
      PI-b induces cell death as compared with control cells. Taken together, our
      present observations strongly suggest that the combinatory treatment with PI
      polyamides targeting KCNQ1OT1 might be a novel therapeutic strategy to cure
      patients with tumors over-expressing KCNQ1OT1.

PMID- 25998556
TI  - Preoperative Anemia as an Independent Prognostic Indicator of Papillary Renal
      Cell Carcinoma.
AB  - OBJECTIVES: Preoperative anemia has been proposed as a prognostic factor for
      clear cell renal cell carcinoma. We evaluate its role in papillary renal cell
      carcinoma (pRCC). METHODS: At 2 institutions, patients who underwent complete
      resection of localized (T1-3 N0/+ M0) pRCC by radical or partial nephrectomy were
      retrospectively reviewed in this study. Anemia was defined as hemoglobin < 13.5
      g/dL in men and < 12 g/dL in women. The associations of preoperative anemia with
      clinical and pathologic variables were assessed using the Student t, Wilcoxon
      rank-sum, and chi-square tests. Univariable and multivariable analyses using the
      Kaplan-Meier method and the Cox regression model were performed to determine
      factors that were associated with recurrence-free survival (RFS), cancer-specific
      survival (CSS), and overall survival (OS). RESULTS: Our final cohort included 352
      patients. Compared with patients without anemia, patients with anemia were older
      and more likely to have larger tumor size and higher Fuhrman grade. Kaplan-Meier
      curves showed that patients with preoperative anemia had significantly worse RFS,
      CSS, and OS than patients without anemia (log-rank test, all P < .001).
      Multivariable analyses revealed that anemia was an independent prognostic factor
      in terms of RFS, CSS, and OS (all P < .001). CONCLUSIONS: Preoperative anemia is
      an important independent prognostic factor associated with an increased risk of
      recurrence and mortality in patients after surgery with a curative intent for
      localized pRCC. Consideration of preoperative anemia could provide urologists
      additional prognostic information in patients with pRCC.

PMID- 25998557
TI  - BK Virus-Associated Invasive Urothelial Carcinoma With Prominent Micropapillary
      Carcinoma Component in a Cardiac Transplant Patient: Case Report and Review of
      Literature.

PMID- 25998558
TI  - Flower evolution of alpine forbs in the open top chambers (OTCs) from the Qinghai
      Tibet Plateau.
AB  - Effects of global changes on biodiversity have been paid more and more attention
      world widely, and the open top chambers (OTCs) are the most common tools to study
      the effects of climatic warming on plant diversity. However, it remains unclear
      how flowers evolve under environmental changes, which could help us to understand
      the changes of plant diversity in the OTCs. We compared the insect diversity and
      pollen:ovule (P/O) ratio of eight outcrossing species with different life
      histories inside and outside the OTCs on the Qinghai-Tibet Plateau, to examine
      the effects induced by OTCs on the evolution of floral traits. In the OTCs, P/O
      ratio decreased in annuals, but increased in perennials, indicating an overall
      trend toward selfing in annuals. We found that the insect diversity differed
      significantly inside and outside the OTCS, with decreases of dipteran insects and
      bees. We concluded that changes of P/O ratio in the studied plant species might
      result from pollination failure, which might be the results of mismatch between
      flowering time and pollinator activities. We also suggested annuals might be in a
      more extinction risk than perennials in OTCs, if strong inbreeding depression
      occurs in these annual outcrossing plants. 

PMID- 25998559
TI  - The Relative Importance of Domain Applicability Metrics for Estimating Prediction
      Errors in QSAR Varies with Training Set Diversity.
AB  - In QSAR, a statistical model is generated from a training set of molecules
      (represented by chemical descriptors) and their biological activities (an
      "activity model"). The aim of the field of domain applicability (DA) is to
      estimate the uncertainty of prediction of a specific molecule on a specific
      activity model. A number of DA metrics have been proposed in the literature for
      this purpose. A quantitative model of the prediction uncertainty (an "error
      model") can be built using one or more of these metrics. A previous publication
      from our laboratory ( Sheridan , R. P. J. Chem. Inf. MODEL: 2013 , 53 , 2837 -
      2850 ) suggested that QSAR methods such as random forest could be used to build
      error models by fitting unsigned prediction errors against DA metrics. The QSAR
      paradigm contains two useful techniques: descriptor importance can determine
      which DA metrics are most useful, and cross-validation can be used to tell which
      subset of DA metrics is sufficient to estimate the unsigned errors. Previously we
      studied 10 large, diverse data sets and seven DA metrics. For those data sets for
      which it is possible to build a significant error model from those seven metrics,
      only two metrics were sufficient to account for almost all of the information in
      the error model. These were TREE_SD (the variation of prediction among random
      forest trees) and PREDICTED (the predicted activity itself). In this paper we
      show that when data sets are less diverse, as for example in QSAR models of
      molecules in a single chemical series, these two DA metrics become less important
      in explaining prediction error, and the DA metric SIMILARITYNEAREST1 (the
      similarity of the molecule being predicted to the closest training set compound)
      becomes more important. Our recommendation is that when the mean pairwise
      similarity (measured with the Carhart AP descriptor and the Dice similarity
      index) within a QSAR training set is less than 0.5, one can use only TREE_SD,
      PREDICTED to form the error model, but otherwise one should use TREE_SD,
      PREDICTED, SIMILARITYNEAREST1.

PMID- 25998560
TI  - Dermatological disorders in Tuvalu between 2009 and 2012.
AB  - There is a distinct lack of knowledge on the prevalence of skin disorders in
      Tuvalu. The aim of the current study was to assess the prevalence of cutaneous
      diseases and to evaluate access dermatological care in Tuvalu. Cutaneous
      disorders in the people of Tuvalu between 2009 and 2012 were examined. The most
      common skin conditions were eczema/dermatitis, superficial fungal infections,
      impetigo, carbuncles, furuncles, folliculitis, acne, scabies, warts and keloids.
      Infrequent skin conditions included infectious granulomatous disease, albinism,
      actinic keratosis, skin cancer, cutaneous lupus erythematosus and mammary Paget's
      disease, which required medical attention. This is the first epidemiological
      report on skin disorders in the southwest Pacific Island, Tuvalu. 

PMID- 25998561
TI  - A tumor-penetrating recombinant protein anti-EGFR-iRGD enhance efficacy of
      paclitaxel in 3D multicellular spheroids and gastric cancer in vivo.
AB  - It has been a major challenge for drug penetration in solid tumor tissues because
      of the complicated tumor microenvironment. We have previously constructed a
      protein of bispecific targets and high permeability named anti-EGFR-iRGD and
      investigated its inhibiting cell proliferation of gastric cancer. Paclitaxel
      (PTX) is widely used for treating various kinds of cancer. In this paper, we
      investigated the effects of anti-EGFR-iRGD in combination with chemotherapeutic
      drugs including PTX in epidermal growth factor receptor highly expressing gastric
      cancer. We demonstrated the therapeutic efficacy of PTX combined with anti-EGFR
      iRGD on monolayer cells (2D), multicellular spheroids (3D) and tumor-bearing mice
      for the first time and investigated the mechanism of this synergy effect. Our
      results provide impetus for further studies to use anti-EGFR-iRGD with standard
      cytotoxic treatment regimens for enhancing therapy of gastric cancer patients. 

PMID- 25998562
TI  - Kinetics of co-crystal formation with caffeine and citric acid via liquid
      assisted grinding analyzed using the distinct element method.
AB  - The kinetics of co-crystal formation of caffeine (CF) with citric acid (CTA) was
      evaluated. Ball milling of CF and CTA in molar ratios of 4:1, 3:1, 2:1, 1:1, 1:2,
      1:3, and 1:4 was performed by the liquid-assisted grinding (LAG) method. The
      samples were characterized by powder X-ray diffraction (PXRD), Fourier transform
      infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Two
      types of co-crystals (co-crystal-1, a 1:1 CF-CTA co-crystal; and co-crystal-2, a
      new co-crystal form) were obtained. The kinetic characteristics of this new co
      crystal formation were assessed by calculating the ball impact energy and force
      using the distinct element method (DEM) simulations. The results indicated that
      co-crystal-2 creation occurred under a condition in which the ball impact force
      exceeded a certain threshold value. Moreover, the total ball impact energy was
      positively correlated with co-crystal formation, exhibiting a higher ball impact
      force than the threshold value. The kinetics of co-crystal-2 formation was almost
      consistent with the Jander equation. Consequently, co-crystal-2 formation could
      be explained according to a three-dimensional diffusion mechanism. 

PMID- 25998564
TI  - A painful pigmented nodule in a patient with metastatic melanoma.

PMID- 25998565
TI  - Concordance between responses to questionnaire scenarios and actual treatment to
      repair or replace dental restorations in the National Dental PBRN.
AB  - OBJECTIVE: To quantify the agreement between treatment recommended during
      hypothetical clinical scenarios and actual treatment provided in comparable
      clinical circumstances. METHODS: A total of 193 practitioners in the National
      Dental Practice-Based Research Network participated in both a questionnaire and a
      clinical study. The questionnaire included three hypothetical scenarios about
      treatment of existing restorations. Clinicians then participated in a clinical
      study about repair or replacement of existing restorations. We quantified the
      overall concordance between their questionnaire responses and what they did in
      actual clinical treatment. RESULTS: Practitioners who recommended repair (instead
      of replacement) of more scenario restorations also had higher repair percentages
      in clinical practice. Additionally, for each of the three hypothetical scenario
      restorations, practitioners who recommended repair had higher repair percentages
      in clinical practice. CONCLUSIONS: The questionnaire scenarios were a valid
      measure of clinicians' tendency to repair or replace restorations in actual
      clinical practice. CLINICAL IMPLICATIONS: Although there was substantial
      variation in practitioners' tendency to repair or replace restorations, responses
      to questionnaire scenarios by individual practitioners were concordant with what
      they did in actual clinical practice.

PMID- 25998566
TI  - Editorial.

PMID- 25998567
TI  - LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1
      activation.
AB  - Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth,
      is activated downstream of growth factors, energy signalling and intracellular
      essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the
      lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA
      (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and
      mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified
      the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1
      4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes,
      leading to uptake of Leu into lysosomes, and is required for mTORC1 activation
      via V-ATPase following EAA or Leu stimulation. These results demonstrate a
      functional Leu transporter at the lysosome, and help explain the inside-out
      lysosomal activation of mTORC1 by Leu/EAA. 

PMID- 25998568
TI  - RAGE-ligands axis: A new 'driving force' for cigarette smoke-induced airway
      inflammation in COPD?
AB  - Receptor for advanced glycation end products (RAGE) was recently shown to
      contribute to cigarette smoke (CS)-induced airway inflammation in chronic
      obstructive pulmonary disease (COPD). In this study, RAGE small interfering
      ribonucleic acid (RNA) transfection attenuated increased messenger RNA levels of
      common RAGE ligands HMGB1, S100A8, S100A9 and S100A12, but not S100B following
      exposure to CS extract. Our findings and those from recent studies suggest a
      positive feedback involving RAGE and its ligands as a new 'driving force' for CS
      induced airway inflammation in COPD. 

PMID- 25998569
TI  - A multisystem diagnostic mystery: unilateral weakness, a rash, and
      lymphadenopathy.

PMID- 25998570
TI  - A Case of Complete Adult-Onset Kawasaki Disease: A Review of Pathogenesis and
      Classification.
AB  - Kawasaki disease (KD) is an acute systemic vasculitis that occurs primarily in
      children and rarely in adults, possibly after bacterial or viral infections in
      genetically susceptible hosts. KD may frequently be undiagnosed especially in
      adult patients without the presence of all the classical clinical criteria
      (incomplete or atypical KD). In addition, many differential diagnoses could be
      considered. Here, we report a case of KD in an adult patient with clinical
      features characteristic of the classical form. KD requires a long-term management
      in both paediatric and adult patients, in order to avoid complications that could
      follow both the acute and retrospective diagnoses of KD.

PMID- 25998571
TI  - Phantom Remodeling Effect of Dorsal Root Entry Zone Lesioning in Phantom Limb
      Pain Caused by Brachial Plexus Avulsion.
AB  - BACKGROUND: Dorsal root entry zone (DREZ) lesioning has been reported to be
      effective for phantom limb pain caused by brachial plexus avulsion pain. Most
      reports on DREZ lesioning for brachial plexus avulsion pain have focused on the
      results of pain relief without a detailed description of phantom sensations
      following DREZ lesioning. MATERIALS AND METHODS: Two patients (1 with amputation
      and the other nonamputated) with chronic intractable phantom limb pain caused by
      brachial plexus avulsion underwent DREZ lesioning on the avulsed segments of the
      cervical spinal cords. Changes of the phantom limb were observed. RESULTS:
      Immediately following DREZ lesioning, the phantom limb pain disappeared in the
      amputee, the phantom arm was shortened and the phantom hand disappeared. The
      other patient with the nonamputated arm reported an immediate 50% reduction in
      the size of the phantom hand, and pain relief was up to 70% of the preoperative
      phantom limb pain. There was no further change in the phantom arm and hand during
      the follow-up of 1.5-2 years. CONCLUSIONS: The phantom arms and hands showed a
      prompt shortening and reduction in size, rather than a disappearance, following
      successful DREZ lesioning in patients with chronic phantom limb pain caused by
      brachial plexus avulsion.

PMID- 25998572
TI  - A randomized trial to assess the pharmacodynamics and pharmacokinetics of a
      single dose of an extended-release aspirin formulation.
AB  - AIMS: Low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention
      reduces cardiovascular disease mortality risk. ASA acetylates cyclooxygenase in
      the portal circulation and is rapidly (half-life, 20 min) hydrolyzed. Certain
      patients with cardiovascular disease may exhibit high on-therapy platelet
      reactivity as a result of high platelet turnover, a process whereby platelets are
      produced and are active beyond the duration of antiplatelet coverage provided by
      once-daily immediate-release (IR) ASA. A once-daily, extended-release (ER) ASA
      formulation using ER microcapsule technology was developed to release ASA over
      the 24-h dosing interval and reduce maximal plasma concentrations to spare
      peripheral endogenous endothelial prostacyclin production. METHODS: Healthy
      adults (n = 50) were randomized in a crossover study to receive two different ER
      ASA single doses (up to 325 mg) and two different IR-ASA single doses (up to 81
      mg) in four periods, each separated by >=14 days. Pharmacodynamics was assessed
      by measuring serum thromboxane B2 (TXB2), urine 11-dehydro-TXB2, and arachidonic
      acid-induced platelet aggregation. Pharmacokinetics was determined for ASA and
      salicylic acid (SA). RESULTS: Both formulations produced dose-dependent
      inhibition on all pharmacodynamic parameters. Marked inhibition of TXB2 and 11
      dehydro-TXB2 was maintained over the 24-h dosing interval after a dose of >=81 mg
      ER-ASA or >=40 mg IR-ASA. The dose required to achieve 50% of maximum TXB2
      inhibition with ER-ASA was 49.9 mg versus 29.6 mg for IR-ASA, for a similar
      maximum pharmacodynamic effect (98.9% TXB2 inhibition). This suggests that an
      approximately twofold greater ER-ASA dose (162.5 mg) is necessary to obtain the
      same response as that of IR-ASA 81 mg. Peak ASA concentrations were lower and
      Tmax was longer with ER-ASA versus IR-ASA. Administration of IR-ASA resulted in a
      dose-normalized mean Cmax of ASA that was approximately sixfold higher than that
      for ER-ASA and a Cmax of SA approximately two- to threefold higher than that for
      ER-ASA. CONCLUSION: Both ASA formulations showed dose-dependent antiplatelet
      activity. Compared with the IR-ASA, ER-ASA released active drug more slowly,
      resulting in prolonged absorption and lower systemic drug concentrations, which
      is expected for an ER (24-h) formulation.

PMID- 25998573
TI  - Expression and Polymorphisms of Lysosome-Associated Protein Transmembrane 5
      (LAPTM5) in Patients with Systemic Lupus Erythematosus in a Chinese Population.
AB  - Lysosome-associated protein transmembrane 5 (LAPTM5) have been demonstrated a
      role in the prevention of lymphocyte hyperactivation, and its deficiency is
      involved in the immunological dysfunction of mouse models. The aim of this study
      was to detect mRNA expression of LAPTM5 in peripheral blood mononuclear cells
      (PBMCs) from patients with systemic lupus erythematosus (SLE), and to assess
      association between LAPTM5 single nucleotide polymorphisms (SNPs) (rs10798801,
      rs4614309, rs1188348, and rs1188349) and SLE in a Chinese population. Real-time
      transcription-polymerase chain reaction analysis was used to determine expression
      of LAPTM5 mRNA in PBMCs from 132 patients with SLE and 62 healthy controls.
      LAPTM5 mRNA expression decreased in SLE patients (n = 71) compared with healthy
      controls (n = 58) (p = 3.68 * 10(-5)). The expression of LAPTM5 mRNA in SLE
      patients with lupus nephritis (LN) (n = 35) was lower than in those without LN (n
      = 36) (p = 0.004). The expression level of LAPTM5 correlated with serum total
      protein (r(s) = 0.41, p = 0.027) and negatively correlated with 24-h proteinuria
      (r(s) = -0.45, p = 0.027). LAPTM5 SNPs (rs10798801, rs4614309, rs1188348, and
      rs1188349) was also analyzed by restriction fragment length polymorphism (RFLP)
      in 380 SLE patients and 460 healthy controls. No significant difference in the
      genotype or allele frequencies for LAPTM5 SNPs was detected in 380 SLE patients
      and 460 healthy controls (p > 0.05). Substantially low frequency of GGAT
      haplotype was observed in SLE patients (p < 0.001). It is concluded that
      insufficient expression of LAPTM5 may take part in the pathogenesis of SLE and
      contribute to the severity of the disease, and none of LAPTM5 polymorphisms
      contributes significantly to SLE susceptibility in a Chinese population.

PMID- 25998574
TI  - The prevalence of long-term symptoms of depression and anxiety after breast
      cancer treatment: A systematic review.
AB  - OBJECTIVES: It is unclear whether breast cancer survivors have a higher risk of
      long-term symptoms of depression or anxiety. The aim of this study was to
      systematically review the evidence about long-term symptoms of depression and
      anxiety in breast cancer survivors. STUDY DESIGN: Systematic review. MAIN OUTCOME
      MEASURES: PubMed, Embase, Cochrane and PsycINFO were searched for studies with at
      least 100 survivors >=1 year after diagnosis, and which used common
      questionnaires measuring symptoms of depression or anxiety, by two independent
      reviewers. The quality was assessed with the NIH 'Quality Assessment Tool'
      checklist. Prevalence of symptoms of depression and anxiety was compared to time
      since diagnosis, available control groups and a general female population.
      RESULTS: Seventeen articles were included in this review with an average quality
      score of 57% (range 38-86%). The prevalence of symptoms of depression varied from
      9.4% to 66.1% and of anxiety from 17.9% to 33.3%. The results on the depression
      scale suggested an increase in risk of symptoms of depression for breast cancer
      survivors at one year after diagnosis, which decreases over the ensuing years.
      Symptoms of anxiety were not more prevalent among the women with early stage
      breast cancer. CONCLUSIONS: This review suggests a higher prevalence of symptoms
      of depression among breast cancer survivors than among the general female
      population, persistent over more than 5 years after diagnosis. Health care
      providers should be aware of this. There was no indication for an increased
      prevalence of symptoms of anxiety among breast cancer survivors.

PMID- 25998575
TI  - miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and
      invasion.
AB  - Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis,
      and survival in non-small-cell lung cancer (NSCLC). Several previous reports have
      demonstrated that microRNAs affect gene expression through interaction between
      their seed region and the 3'-untranslated region of the target mRNA, resulting in
      post-transcriptional regulation. The aim of this study was to identify miRNAs
      that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell
      lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western
      blotting after transfection with MTA1 mimics. A luciferase reporter assay was
      established to test the direct connection between MTA1 and its upstream miRNAs.
      Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine analysis, and colony
      formation assay. Cell migration and invasive capacity were evaluated by wound
      healing assay and transwell assay. The miRNA/MTA1 axis was also probed by
      quantitative RT-PCR and western blotting in samples from eight NSCLC patients.
      Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally
      regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase
      reporter assay, in addition to the demonstration that MTA1 is inversely
      correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found
      to inhibit NSCLC cell proliferation, migration, and invasion, through the same
      mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p
      inhibits the proliferation, migration, and invasion of NSCLC cells through down
      regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC,
      and may provide novel insight into the molecular mechanisms underpinning the
      disease and potential therapeutic targets. 

PMID- 25998577
TI  - Reflecting on 'The complexity of governance change: reforming the governance of
      medical performance in Germany'.

PMID- 25998578
TI  - The combined use of Camellia sinensis and metronomic zoledronate in 4T1 mouse
      carcinoma against tumor growth and metastasis.
AB  - In previous studies, we demonstrated that the green tea Camellia sinensis (CS)
      water extract had potent antitumor and antimetastatic effects on 4T1 breast
      cancer. The metronomic regimen (0.0125 mg/kg twice a week for 4 weeks) of
      zoledronate (ZOL) was found to be effective in decreasing tumor burden and
      metastasis as compared with conventional regimen. The aim of the present study
      was to investigate the antitumor, antimetastatic and anti-osteolytic effects of
      the combined use of CS water extract and metronomic ZOL against 4T1 breast
      carcinoma in vitro and in vivo. The results demonstrated that the combination of
      CS+ZOL exerted a more potent effect on lung and liver by decreasing tumor burden
      and metastasis, when compared to CS or metronomic ZOL as monotherapies. The
      combination of CS+ZOL demonstrated optimal bone protection against breast cancer
      induced osteolysis for the three groups of CS, ZOL and CS+ZOL. The in vitro
      results further demonstrated that ZOL enhanced CS-induced apoptosis in 4T1 cells
      as assessed by the Annexin V-FITC/PI staining and caspase-3 activity assays. In
      addition, the combined use of CS+ZOL significantly inhibited 4T1 cell migration.
      Mechanistic studies showed that the enzyme levels of matrix metalloproteinases
      (MMP)-2 and MMP-9 were suppressed significantly by CS+ZOL. In conclusion, to the
      best of our knowledge, this is the first study to investigate the novel combined
      application of herbal extract CS and chemotherapy ZOL in 4T1 breast cancer. The
      combination of CS plus metronomic ZOL demonstrated significant antitumor,
      antimetastatic and anti-osteolytic effects against breast cancer, and suggested
      potential clinical application for breast cancer patients.

PMID- 25998576
TI  - Organ donor specimens: What can they tell us about type 1 diabetes?
AB  - Type 1 diabetes (T1D) is a chronic disease resulting from the destruction of
      pancreatic beta cells, due to a poorly understood combination of genetic,
      environmental, and immune factors. The JDRF Network for Pancreatic Organ donors
      with Diabetes (nPOD) program recovers transplantation quality pancreas from organ
      donors throughout the USA. In addition to recovery of donors with T1D, non
      diabetic donors include those with islet autoantibodies. Donors with type 2
      diabetes and other conditions are also recovered to aid investigations directed
      at the full spectrum of pathophysiological mechanisms affecting beta cells. One
      central processing laboratory conducts standardized procedures for sample
      processing, storage, and distribution, intended for current and future cutting
      edge investigations. Baseline histology characterizations are performed on the
      pancreatic samples, with images of the staining results provided though whole
      slide digital scans. Uniquely, these high-grade biospecimens are provided without
      expense to investigators, working worldwide, seeking methods for disease
      prevention and reversal strategies. Collaborative working groups are highly
      encouraged, bringing together multiple investigators with different expertise to
      foster collaborations in several areas of critical need. This mini-review will
      provide some key histopathological findings emanating from the nPOD collection,
      including the heterogeneity of beta cell loss and islet inflammation (insulitis),
      beta cell mass, insulin-producing beta cells in chronic T1D, and pancreas weight
      reductions at disease onset. Analysis of variations in histopathology observed
      from these organ donors could provide for mechanistic differences related to
      etiological agents and serve an important function in terms of identifying the
      heterogeneity of T1D. 

PMID- 25998579
TI  - Correlates of hair loss in adult women of African descent in London, U.K.:
      findings of a cross-sectional study.

PMID- 25998580
TI  - Thrombospondin 1 Modulates Monocyte Properties to Suppress Intestinal Mucosal
      Inflammation.
AB  - Monocytes (Mos) play an important role in the pathogenesis of intestinal mucosal
      inflammation. This study aims to investigate the mechanism by which the
      intestinal epithelial cell-derived thrombospondin 1 (TSP1) modulates Mo
      properties and regulates intestinal inflammatory responses. In this study, the
      production of TSP1 by intestinal epithelial cells was evaluated by quantitative
      real-time PCR and Western blotting. The properties of Mos were analyzed by flow
      cytometry. A mouse model of colitis was created to assess the role of epithelium
      derived TSP1 in the suppression of intestinal inflammation. The results
      demonstrated that mouse intestinal epithelial cells (IECs) expressed TSP1, which
      was markedly upregulated by butyrate or feeding with Clostridium butyricum.
      Coculture of the butyrate-primed IECs and Mos or exposure of Mos to TSP1 in the
      culture induced the expression of transforming growth factor (TGF)-beta in Mos.
      These TGF-beta+ Mos had tolerogenic properties that could promote generation of
      inducible regulatory T cells. Adoptive transfer with TSP1-primed Mos, or feeding
      C. butyricum could prevent experimental colitis in mice. In summary, C. butyricum
      induces intestinal epithelial cells to produce TSP1 and induces TGF-beta+ Mos,
      which further suppress experimental colitis in mice. The results implicate that
      the administration of C. butyricum or butyrate may have the potential to
      ameliorate chronic intestinal inflammation through inducing immunosuppressive
      Mos. 

PMID- 25998581
TI  - Ureteric colic: evidence empowers responsible treatment.

PMID- 25998583
TI  - Individually prescribed diet is fundamental to optimize nutritional treatment in
      geriatric patients.
AB  - BACKGROUND & AIMS: Malnutrition is a well-recognized problem in geriatric
      patients. Individually prescribed diet is fundamental to optimize nutritional
      treatment in geriatric patients. The objective of this study was to investigate
      routines regarding dietary prescriptions and monitoring of food intake in
      geriatric patients and to see how well the prescribed diet conforms to the
      patients' nutritional status and ability to eat. A further aim was to identify
      the most common reasons and factors interacting with patients not finishing a
      complete meal. METHODS: This study combines two methods using both qualitative
      and quantitative analysis. Patients (n = 43; 82.5 +/- 7.5 yrs; 60% females) at
      four geriatric wards performed a two-day dietary record, assisted by a dietician.
      Nurses and assistant nurses at each ward participated in a semi-structured
      interview regarding prescription of diets and portion size for the patients.
      RESULTS: The prescribed diet differed significantly (P < 0.01) from a diet based
      upon the patient's nutritional status and ability to eat. Only 30% of the
      patients were prescribed an energy-enriched diet in contrast to 60% that was in
      need of it. The most common reason for not finishing the meal was lack of
      appetite. Diet prescription for the patient was based upon information about
      eating difficulties identified in the Mini Nutritional Assessment-Short Form (MNA
      SF) at admission and the type of diet that was prescribed on a previous ward.
      Monitoring of the patients' food intake was described as a continuous process
      discussed daily between the staff. CONCLUSION: Patients' nutritional status and
      to what extent they were able to eat a complete meal was not routinely considered
      when prescribing food and monitoring food intake in this study. By making use of
      this information the diet could be tailored to the patients' needs, thereby
      improving their nutritional treatment.

PMID- 25998582
TI  - Medical expulsive therapy in adults with ureteric colic: a multicentre,
      randomised, placebo-controlled trial.
AB  - BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that
      the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage
      for people managed expectantly for ureteric colic, but emphasised the need for
      high-quality trials with wide inclusion criteria. We aimed to fulfil this need by
      testing effectiveness of these drugs in a standard clinical care setting.
      METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited
      adults (aged 18-65 years) undergoing expectant management for a single ureteric
      stone identified by CT at 24 UK hospitals. Participants were randomly assigned by
      a remote randomisation system to tamsulosin 400 MUg, nifedipine 30 mg, or placebo
      taken daily for up to 4 weeks, using an algorithm with centre, stone size (<=5 mm
      or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation
      covariates. Participants, clinicians, and trial personnel were masked to
      treatment assignment. The primary outcome was the proportion of participants who
      did not need further intervention for stone clearance within 4 weeks of
      randomisation, analysed in a modified intention-to-treat population defined as
      all eligible patients for whom we had primary outcome data. This trial is
      registered with the European Clinical Trials Database, EudraCT number 2010-019469
      26, and as an International Standard Randomised Controlled Trial, number
      69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned
      1167 participants, 1136 (97%) of whom were included in the primary analysis (17
      were excluded because of ineligibility and 14 participants were lost to follow
      up). 303 (80%) of 379 participants in the placebo group did not need further
      intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group
      (adjusted risk difference 1.3% [95% CI -5.7 to 8.3]; p=0.73) and 304 (80%) of 379
      in the nifedipine group (0.5% [-5.6 to 6.5]; p=0.88). No difference was noted
      between active treatment and placebo (p=0.78), or between tamsulosin and
      nifedipine (p=0.77). Serious adverse events were reported in three participants
      in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one
      had malaise, headache, and chest pain; and one had severe chest pain, difficulty
      breathing, and left arm pain) and in one participant in the placebo group
      (headache, dizziness, lightheadedness, and chronic abdominal pain).
      INTERPRETATION: Tamsulosin 400 MUg and nifedipine 30 mg are not effective at
      decreasing the need for further treatment to achieve stone clearance in 4 weeks
      for patients with expectantly managed ureteric colic. FUNDING: UK National
      Institute for Health Research Health Technology Assessment Programme.

PMID- 25998584
TI  - Lifestyle patterns in early pregnancy linked to gestational diabetes mellitus
      diagnoses when using IADPSG criteria. The St Carlos gestational study.
AB  - Early-pregnancy lifestyle (EPL) could influence the development of gestational
      diabetes mellitus(GDM), depending on the diagnostic criteria used. OBJECTIVE: We
      studied EPL in 1750 pregnant women using Carpenter-Coustan criteria(CCc), and in
      1526 with the International Association of Diabetes and Pregnancy Study Groups
      criteria(IADPSGc). METHODS: GDM risk factors were assessed in women between 24
      and 28 weeks of gestational age during two consecutive years. A semiquantitative
      frequent-food-consumption questionnaire was used to evaluate lifestyle during
      pregnancy. Multiple logistic regression analysis was conducted to assess GDM risk
      with different lifestyle patterns. RESULTS: Using IADPSGc, the GDM ORs (95%CI)
      for intake/week were: nuts >3 times: 0.59 (0.39-0.91; p < 0.015), refined cereals
      <=1 serving: 0.72(0.58-0.89; p < 0.003), juices <4 servings: 0.77 (0.62-0.95; p <
      0.017), cookies and pastries <4 servings: 0.71(0.57-0.89; p < 0.003) as compared
      to opposite habits. No significant nutritional patterns were found to be
      significant using CCc. The OR (95%CI) for GDM with none of the four risk patterns
      as compared to having three-four risk factors was 0.21(0.07-0.62; p < 0.005),
      remaining significant after stratification by BMI, age, obstetric events, parity
      and family history. The multiple logistic regression model including nutritional
      categories and pregestational BMI, age, obstetric history, parity,
      personal/family history, had an area under the curve(AUC) of the receiver
      operating curve(ROC) for the probability to predict GDM of 0.66 (CI 95%: 0.63
      0.69; p < 0.001). CONCLUSION: Our study is the first to identify four early
      pregnancy nutritional patterns associated with the GDM when using IADPSGc.
      Adherence to a low-risk nutritional pattern from early pregnancy on could be an
      effective strategy for GDM prevention.

PMID- 25998585
TI  - Functionalization of graphene oxide nanostructures improves photoluminescence and
      facilitates their use as optical probes in preclinical imaging.
AB  - Recently reported photoluminescent nanographene oxides (nGOs), i.e. nanographene
      oxidised with a sulfuric/nitric acid mixture (SNOx method), have tuneable
      photoluminescence and are scalable, simple and fast to produce optical probes.
      This material belongs to the vast class of photoluminescent carbon
      nanostructures, including carbon dots, nanodiamonds (NDs), graphene quantum dots
      (GQDs), all of which demonstrate a variety of properties that are attractive for
      biomedical imaging such as low toxicity and stable photoluminescence. In this
      study, the nGOs were organically surface-modified with poly(ethylene glycol)
      poly(ethylene imine) (PEG-PEI) copolymers tagged with folic acid as the affinity
      ligand for cancer cells expressing folate receptors. The functionalization
      enhanced both the cellular uptake and quantum efficiency of the photoluminescence
      as compared to non-modified nGOs. The nGOs exhibited an excitation dependent
      photoluminescence that facilitated their detection with a wide range of
      microscope configurations. The functionalized nGOs were non-toxic, they were
      retained in the stained cell population over a period of 8 days and they were
      distributed equally between daughter cells. We have evaluated their applicability
      in in vitro and in vivo (chicken embryo CAM) models to visualize and track
      migratory cancer cells. The good biocompatibility and easy detection of the
      functionalized nGOs suggest that they could address the limitations faced with
      quantum dots and organic fluorophores in long-term in vivo biomedical imaging. 

PMID- 25998587
TI  - Official journal of the professional sections of the canadian diabetes
      association.

PMID- 25998586
TI  - Childhood cancer in Argentina: Survival 2000-2007.
AB  - INTRODUCTION: Information on the epidemiology of childhood cancer in Latin
      America is limited. The Argentinean Oncopaediatric Registry (ROHA) is a
      population-based registry active since 2000. This paper describes the 3-year
      survival experience of children diagnosed with cancer in Argentina during 2000
      2007 by major morphological subgroup, age, sex, and geographical region of
      residence. METHODS: Newly diagnosed paediatric cancer cases are registered in
      ROHA (estimated coverage is 93% of the country's cases). Three-year overall
      survival was estimated using Kaplan-Meier methods. Univariate Cox models were
      used to compare subgroup survival. RESULTS: Between 2000 and 2007, a total of
      10,181 new cancer diagnoses in children aged 0-14 years were reported to the
      registry. Three-year overall survival (95%CI) for all cancers was 61.7% (60.7;
      62.7). Specific survival for the most frequent morphological types was:
      leukaemias 63.3% (61.6; 64.9), lymphomas and related neoplasms 75.3% (72.7;
      77.7), brain neoplasms 46.3% (43.9; 48.7), soft-tissue sarcomas 52.3% (48.0;
      56.5), neuroblastomas 49.6% (44.6; 54.3), renal tumours 76.7% (72.2; 80.6), and
      malignant bone tumours 47.2% (42.3; 51.9). Overall survival was associated with
      age but not sex and varied by geographical region. Compared to other regions,
      patients who resided in the capital city had a significantly higher survival:
      69.6% (65.8; 73.0) versus 63.5% (59.4; 67.4) in Patagonia, 63.2% (61.9; 64.5) in
      the central region, 58.0% (54.2; 61.7) in Cuyo, 55.6% (52.5; 58.6) in the north
      east, and 55.4% (52.4; 58.2) in the north-west (all P values <0.005).
      CONCLUSIONS: Of children diagnosed with cancer in Argentina, 62% survived at
      least 3 years after diagnosis. Even though this figure is lower than that
      reported for more developed countries, survival patterns by diagnosis, age and
      sex were quite similar. Survival was lower in the two northern regions, which are
      areas with higher poverty levels.

PMID- 25998588
TI  - Riding the waves of change in the diabetes community.

PMID- 25998589
TI  - Diabetes quality of care in academic endocrinology practice: a descriptive study.
AB  - OBJECTIVE: To describe the quality of diabetes care delivered by academic
      endocrinologists practicing at 4 teaching hospitals affiliated with a single
      medical school. METHODS: Up to 30 patients who first saw an endocrinologist for
      an ambulatory consultation for diabetes between January 2004 and December 2005
      were randomly selected for chart review. Process and intermediate measures of
      quality of care were abstracted. RESULTS: There were 417 patient charts available
      for analysis. Quality of care was generally high, with 61% of patients achieving
      a glycated hemoglobin of <=7.0%, 77% achieving blood pressure <=130/80 mm Hg and
      73% achieving a low-density lipoprotein cholesterol level of <=2.5 mmol/L. More
      than 80% of patients had had eye examinations, microalbuminuria screening and
      foot examinations. There were no significant differences in quality between
      hospitals. CONCLUSIONS: The quality of diabetes care delivered by academic
      endocrinologists in this setting was high and approached the "ideal" levels of
      care recommended by practice guidelines. Compared to past studies in both the
      primary and specialist care settings, the results show that high-quality care can
      be delivered in routine academic clinical practice without having previously
      instituted a specific quality improvement program.

PMID- 25998590
TI  - Diabetes and related metabolic conditions in an aboriginal cree community of
      quebec, Canada.
AB  - OBJECTIVE: We evaluated the prevalence of type 2 diabetes, obesity and metabolic
      syndrome according to International Diabetes Federation criteria in the First
      Nations Cree community of Mistissini, Quebec. METHODS: A cross-sectional study of
      172 adults was performed as part of a broader regional environmental study.
      RESULTS: Type 2 diabetes, hyperinsulinemia and abdominal obesity were documented
      in 20%, 70% and 91% of participants, respectively. The prevalence of metabolic
      syndrome was 54%, with the main profile including abnormal plasma glucose levels
      (60%) associated with high triacylglycerol (40%). Women displayed the highest
      prevalence of abdominal obesity (99%). In both sexes, waist circumference was
      clearly associated with other metabolic parameters, such as blood glucose and
      lipid profile (p<0.0001). However, a significant proportion of the population
      (13%), especially women, showed high waist circumference with no metabolic
      disturbances. CONCLUSION: Among the Cree population of Mistissini, the results
      suggest that the high prevalence of abdominal obesity occurs most frequently in
      women, and earlier in women than in men. Subsequent metabolic disturbances
      associated with metabolic syndrome develop with age, supporting the core role of
      abdominal obesity in the cascade of events leading to diabetes and cardiovascular
      disease.

PMID- 25998591
TI  - Low Prevalence of Elevated ApoB Levels in Patients with Type 2 Diabetes Not
      Receiving Lipid-Lowering Therapy.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in people
      with type 2 diabetes. Apolipoprotein B (apoB) is known to be a better marker of
      CVD risk than low-density lipoprotein cholesterol (LDL-C). This study
      investigated apoB levels in people with type 2 diabetes. METHODS: We obtained
      blood samples from 507 consenting people with type 2 diabetes who were not
      receiving lipid-lowering medication and who had no previous history of CVD.
      Subjects were divided into 3 groups: men (M), women <50 years old (W1) and women
      >=50 years old (W2). Primary analysis examined lipid parameters, specifically
      apoB. Secondary analysis involved classifying patients according to the Canadian
      Diabetes Association's apoB, LDL-C and triglyceride (TG) targets. RESULTS: We
      found a total mean apoB level of 0.92 g/L. Among patients who failed to achieve
      the LDL-C target, 28% of M, 39% of W1 and 30% of W2 met the apoB target. The
      proportions of individuals categorized as being above the LDL-C and apoB targets
      were significantly different in all 3 groups (p<0.01). When LDL-C was below
      target and TG was <1.5 mmol/L, 100% of M and W1 and 93% of W2 met the apoB
      target. CONCLUSIONS: The discordance between the proportions of patients meeting
      LDL-C and apoB targets may lead to patients being erroneously classified. ApoB
      and LDL-C correlate very well when TG is <1.5 mmol/L, but not when >=1.5 mmol/L.
      Approximately one-third of patients met both LDL-C and apoB goals. Thus, not all
      patients with type 2 diabetes should be considered to be at a high risk of CVD.

PMID- 25998592
TI  - Healthy adolescents' social representations of diabetes.
AB  - OBJECTIVE: This study explores healthy adolescents' social representations of
      diabetes in terms of its definition, origins and prevention. METHODS: Focus
      groups were conducted with students in Grades 5, 8 and 10 from 4 francophone
      schools in New Brunswick, Canada. Audiotaped discussions were transcribed and
      categorized using qualitative content analysis (Atlas.ti software). Chi-square
      and Fisher's exact tests were used to determine sex and grade-level differences
      in frequency of category citations. RESULTS: Nineteen focus groups involved 130
      adolescents. Students defined diabetes as a disease (13 groups) related to sugar
      (15 groups) and blood (13 groups), but only a few mentioned the role of
      insulin/pancreas, types of diabetes and/or complications. Symptoms/physiological
      manifestations (11 groups), monitoring blood sugar (10 groups) and insulin
      injections (5 groups) were discussed primarily in terms of behaviours observed
      among family and friends with diabetes, demonstrating the importance of social
      environment in their representations. Half of the groups identified heredity,
      age, obesity, physical activity and poor diet as playing a role in developing
      diabetes. Students had a general idea about the importance of good eating habits
      and physical activity in terms of managing and preventing diabetes. Eleven groups
      had the misconception that sugar causes diabetes. Although each focus group had
      at least 1 adolescent with a family member affected by the disease, only half of
      the groups cited feeling at risk of diabetes - girls more likely than boys
      (p<=0.05). CONCLUSION: Healthy adolescents in Moncton, New Brunswick, have a
      limited comprehension of diabetes, which could make it difficult for them to take
      preventive action to contain this epidemic disease.

PMID- 25998593
TI  - Piragliatin, an allosteric activator of glucokinase, greatly enhances glucose
      induced pancreatic islet respiration and insulin release.

PMID- 25998594
TI  - Reductions in lipids and CV risk markers in patients with type 2 diabetes treated
      with liraglutide: a meta-analysis.

PMID- 25998595
TI  - O-0544 Exenatide once-weekly versus twice-daily: comparison of diurnal and
      postprandial glucose patterns using continuous glucose monitoring and ambulatory
      glucose profile analysis.

PMID- 25998596
TI  - Ambulatory glucose profile (AGP): development of a common, web-based application
      to record and report continuous glucose monitoring data.

PMID- 25998597
TI  - Emotional eating and risk of overweight among teenage girls.

PMID- 25998598
TI  - Preservation of human islet function in vitro through EMc reestablishment.

PMID- 25998599
TI  - Development and implementation of diabetes guidelines for elderly residents in
      long-term care facilities in Nova scotia.

PMID- 25998600
TI  - Heroes against diabetes in Africa.

PMID- 25998601
TI  - Extramyocellular adipose tissue in type 2 diabetes.

PMID- 25998602
TI  - Academic impact rankings of neurosurgical units in the U.K. and Ireland, as
      assessed with the h-index.
AB  - AIM: Our aim is to measure and compare the academic and research output of
      neurosurgical departments across the U.K. and Ireland. METHODS: Using the
      Institute for Scientific Information Web of Science Bibliometric we collated the
      cumulative, h(c) [1950-2014], 10-year, h(10) [2004-2014] and 3-year, h(3) [2012
      2014] data for neurosurgical departments in the U.K. and Ireland for each of the
      following: number of papers (Np), numbers of citations (Nc) and the h-index.
      RESULTS: In total, 37 neurosurgical departments were found in the U.K. and
      Ireland. We have ranked units according to their h-index. Two units could not be
      ranked as we were unable to separate the neurosurgical department publications
      from that of neurology. Most units maintained their h-index ranking across the
      three time periods. However, some units moved dramatically. We also compared the
      top five departments for each time period. Generally there is very good
      correlation between the three indices of h-index, Np and Nc. The greater the time
      period, the closer these indices correlated. We were also able to document the
      top five papers for each department. CONCLUSION: The h-index is useful for
      ranking neurosurgical departments according to their historical or recent
      publication output. It is particularly useful when restricted to the last 10-year
      period. We have been able to quantify and rank the academic output of
      neurosurgical units across the U.K. and Ireland, except where mentioned. This may
      be of interest to the clinician who wishes to pursue a career in academia or
      research.

PMID- 25998603
TI  - 2014 consensus statement on improving pelvic floor muscle training adherence:
      International Continence Society 2011 State-of-the-Science Seminar.
AB  - AIMS: To summarize the findings and "expert-panel" consensus of the State-of-the
      Science Seminar on pelvic floor muscle training (PFMT) adherence held prior to
      the 41st International Continence Society scientific meeting, Glasgow, 2011.
      METHODS: Summaries of research and theory about PFMT adherence (based on a
      comprehensive literature search) were presented by subject experts at the 2011
      Seminar to generate discussion and guidance for clinical practice and future
      research. Supplemental research, post-seminar, resulted in, three review papers
      summarizing: (1) relevant behavioral theories, (2) adherence measurement,
      determinants and effectiveness of PFMT adherence interventions, and (3) patients'
      PFMT experiences. A fourth, reported findings from an online survey of health
      professionals and the public. RESULTS: Few high-quality studies were found. Paper
      I summarizes 12 behavioral frameworks relevant to theoretical development of PFMT
      adherence interventions and strategies. Findings in Paper II suggest both PFMT
      self-efficacy and intention-to-adhere predict PFMT adherence. Paper III
      identified six potential adherence modifiers worthy of further investigation.
      Paper IV found patient-related factors were the biggest adherence barrier to PFMT
      adherence. CONCLUSION: Given the lack of high-quality studies, the conclusions
      were informed by expert opinion. Adherence is central to short- and longer-term
      PFMT effect. More attention and explicit reporting is needed regarding: (1)
      applying health behavior theory in PFMT program planning; (2) identifying
      adherence determinants; (3) developing and implementing interventions targeting
      known adherence determinants; (4) using patient-centred approaches to evaluating
      adherence barriers and facilitators; (5) measuring adherence, including refining
      and testing instruments; and (6) testing the association between adherence and
      PFMT outcome.

PMID- 25998604
TI  - Generalized Lotka stability.
AB  - The recently developed macroscopic approach to demography describes the age
      distribution of mothers and the net maternity function for a given human
      population entirely in terms of five parameters. Tracking of these parameters
      provides a number of new tools for analyzing populations and predicting their
      future states. Within the macroscopic approach, the new concept of generalized
      Lotka stability is presented in this paper, as an extension of a strong version
      of classic Lotka stability. The two leading parameters of the macroscopic
      approach, the Malthusian parameter r and the perturbation s, are computed from
      population data and plotted in two-dimensional parameter space. Generalized Lotka
      stability is then defined in terms of the movement of the (r,s)-vector over time.
      It may be observed in a number of human populations at specific periods of their
      history. 

PMID- 25998606
TI  - Functional Expression of Aquaporin-2 Tagged with Photoconvertible Fluorescent
      Protein in mpkCCD Cells.
AB  - BACKGROUND: Vasopressin induced trafficking of aquaporin-2 (AQP2) containing
      vesicles has been studied in kidney cell lines using conventional fluorescent
      proteins as tags. However, trafficking of fluorescent tagged AQP2, which
      resembles the vectorial translocation of native AQP2 from cytoplasm to apical
      membrane has not been demonstrated at real time. Using a photoconvertible
      fluorescent protein tag on AQP2 might allow the simultaneous tracking of two
      separate populations of AQP2 vesicle after subcellular local photoconversion.
      METHODS: A spacer was used to link a photoconvertible fluorescent protein (mEos2)
      to the amino-terminus of AQP2. The DNA constructs were expressed in mpkCCD cells.
      The trafficking of chimeric protein was visualized with high speed confocal
      microscopy in 4 dimensions. RESULTS: Chimeric AQP2 expressed in mpkCCD cell
      conferred osmotic water permeability to the cells. Subcellular photoconversion
      with a 405 nm laser pulse converted green chimeras to red chimeras locally.
      Forskolin stimulation triggered chimeric AQP2 to translocate from acidic
      organelles to apical plasma membrane. By serendipity, the rate of apical
      accumulation was found to increase when mEos2 was tagged to the carboxyl-terminus
      in at least one of the AQP2 molecules within the tetramer. CONCLUSION: Functional
      photoconvertible chimeric AQP2 was successfully expressed in mpkCCD cells, in
      which forskolin induced apical trafficking and accumulation of chimeric AQP2. The
      proof-of-concept to monitor two populations of AQP2 vesicle simultaneously was
      demonstrated.

PMID- 25998605
TI  - Effects of palatable cafeteria diet on cognitive and noncognitive behaviors and
      brain neurotrophins' levels in mice.
AB  - The consumption of palatable high-fat and high-sugar foods have increased
      dramatically over the past years. Overconsumption of calorically dense food
      contributes to increasing rates of overweight and obesity that are associated
      with psychiatry disorders, in particular mood and anxiety disorders. This study
      evaluated the impact of palatable cafeteria diet (CAF) intake on cognitive and
      noncognitive behaviors, as well as identified factors related to these behaviors
      through an evaluation of brain neurotrophic factor (BDNF, NGF, and GDNF) levels
      in hippocampus of mice. Male Swiss mice received two different diets during 13
      weeks: standard chow (STA) and highly CAF. Posteriorly, forced swimming test
      (FST), tail suspension test (TST), plus-maze test (PMT), open-field tests (OFT),
      and object recognition task (ORT) were utilized as behavioral tests. In addition,
      brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic
      factor (GDNF), and nerve growth factor (NGF) neurotrophins' levels were evaluated
      in hippocampus of mice. The results demonstrated that mice from the CAF group
      showed a decrease in the immobility time in the FST and TST. Besides, mice in the
      CAF group spent more time in the open arms of the PMT. No significant differences
      were observed in the cognitive behaviors, which were evaluated in the OFT and
      ORT. In addition, the CAF group showed that BDNF and NGF protein levels increased
      in the hippocampus of mice. In conclusion, our data suggest that the consumption
      of palatable high-fat and high-sugar foods induces antidepressant- and anxiolytic
      like behaviors, which can be related with BDNF and NGF expression increases in
      hippocampus of mice in the CAF group. 

PMID- 25998607
TI  - Laparoscopic excision of an adult retroperitoneal cystic lymphangioma coexisting
      with an esophageal hiatus hernia.
AB  - Lymphangiomas are rare cystic tumors that may be present in the retroperitoneum.
      Retroperitoneal lymphangiomas account for approximately 1% of all lymphangiomas.
      We experienced an adult patient with a retroperitoneal cystic lymphangioma
      coexisting with an esophageal hiatus hernia. Abdominal ultrasonography showed a
      cyst in the abdomen of a 76-year-old woman. She was admitted to our clinic
      because of an enlargement of the cyst and epigastric pain after meals. She had a
      long history of heartburn after meals and had not undergone any treatment. She
      had no record of previous illnesses. Computed tomography revealed a single bunch
      cystic tumor with septations, located from the mediastinum to the retroperitoneal
      space. The tumor was not enhanced, and there was no solid part. She was diagnosed
      with a retroperitoneal cyst. Laparoscopic total excision was performed because
      the cyst was increasing in size and the patient had symptoms. The cyst was
      successfully removed. Although laparoscopic excision of retroperitoneal cystic
      lymphangiomas is the treatment of choice, surgical methods should be carefully
      chosen in selected patients.

PMID- 25998609
TI  - Dystrophinopathy mimicking metabolic myopathies.
AB  - Recurrent rhabdomyolysis warrants comprehensive evaluations to search for
      underlying muscle diseases, including metabolic myopathies, LPIN1-myopathy, RYR1
      myopathy, and less commonly muscular dystrophies. The absence of weakness and the
      normal or minimally elevated creatine kinase levels between attacks are typical
      of metabolic myopathies, LPIN1-myopathy, and RYR1-myopathy, while the presence of
      weakness and the highly elevated creatine kinase levels between attacks point
      toward muscular dystrophies. Here we report a 32-year-old man with a one-year
      history of recurrent rhabdomyolysis, who had normal strength, slightly elevated
      baseline creatine kinase level, and normal muscle histopathology. All workups for
      metabolic myopathies, LPIN1-myopathy and RYR1-myopathy were unrevealing. Next
      generation sequencing of muscular dystrophy-related genes revealed a hemizygous
      deletion of exons 17-34 of the dystrophin-encoding gene. Immunohistochemical
      study revealed absent staining for the rod domain of dystrophin. Dystrophinopathy
      should be considered in patients with recurrent rhabdomyolysis despite the
      absence of fixed weakness or highly elevated resting creatine kinase level. 

PMID- 25998608
TI  - In Vivo Confocal Microscopy of the Cornea: New Developments in Image Acquisition,
      Reconstruction, and Analysis Using the HRT-Rostock Corneal Module.
AB  - The optical sectioning ability of confocal microscopy allows high magnification
      images to be obtained from different depths within a thick tissue specimen and is
      thus ideally suited to the study of intact tissue in living subjects. In vivo
      confocal microscopy has been used in a variety of corneal research and clinical
      applications since its development over 25 years ago. In this article we review
      the latest developments in quantitative corneal imaging with the Heidelberg
      Retinal Tomograph with Rostock Corneal Module (HRT-RCM). We provide an overview
      of the unique strengths and weaknesses of the HRT-RCM. We discuss techniques for
      performing 3-D imaging with the HRT-RCM, including hardware and software
      modifications that allow full-thickness confocal microscopy through-focusing
      (CMTF) of the cornea, which can provide quantitative measurements of corneal
      sublayer thicknesses, stromal cell and extracellular matrix backscatter, and
      depth-dependent changes in corneal keratocyte density. We also review current
      approaches for quantitative imaging of the subbasal nerve plexus, which require a
      combination of advanced image acquisition and analysis procedures, including wide
      field mapping and 3-D reconstruction of nerve structures. The development of new
      hardware, software, and acquisition techniques continues to expand the number of
      applications of the HRT-RCM for quantitative in vivo corneal imaging at the
      cellular level. Knowledge of these rapidly evolving strategies should benefit
      corneal clinicians and basic scientists alike.

PMID- 25998610
TI  - Targeted screening for the detection of Pompe disease in patients with
      unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using
      dried blood: A Spanish cohort.
AB  - We aimed to screen for Pompe disease in patients with unclassified limb-girdle
      muscular dystrophy (LGMD) or asymptomatic hyperCKemia using dried blood spot
      (DBS) assays. Subsequently, we aimed to calculate the diagnostic delay between
      initial symptom presentation and the diagnosis. A prospective, multicenter,
      observational study was conducted in 348 patients: 146 with unclassified LGMD and
      202 with asymptomatic or paucisymptomatic hyperCKemia. We quantified levels of
      acid alpha-glucosidase (GAA) from dried blood spots analyzed fluorometrically.
      The test was positive in 20 patients, and Pompe disease was confirmed by genetic
      testing in 16. Undiagnosed Pompe disease was detected in 7.5% of patients with
      LGMD and in 2.5% of patients with persistent, idiopathic elevation of serum
      creatine kinase. The c.-32-13 T > G mutation was found most commonly. The
      diagnostic delay was 15 years on average. In conclusion, DBS tests are useful and
      reliable screening tools for Pompe disease. We recommend the dried blood spot
      test to be included in the diagnostic work-up of patients with unclassified
      myopathies with proximal weakness and/or hyperCKemia of unknown cause and, when
      positive, to define the diagnosis, it will have to be confirmed by biochemical
      and/or molecular genetic analysis.

PMID- 25998611
TI  - Selective response to rituximab in a young child with MuSK-associated myasthenia
      gravis.
AB  - Neuromuscular junction disorders in children are either genetic, such as
      congenital myasthenic syndrome, or autoimmune with circulating antibodies most
      commonly against acetylcholine receptors. There is limited experience recognizing
      and treating children with myasthenia associated with muscle-specific tyrosine
      kinase antibodies. We report a seven-year-old child with intermittent esotropia
      since age 3 months, and two years of progressive and severe diplopia, dysarthria,
      dysphagia, and facial weakness. Acetylcholine receptor antibodies and genetic
      testing for congenital myasthenic syndrome were negative. Muscle specific
      tyrosine kinase antibodies were significantly elevated. Ophthalmoplegia and
      bulbar weakness were refractory to treatment with acetylcholinesterase
      inhibitors, corticosteroids and IVIg but completely resolved following treatment
      with rituximab. Her neurologic examination remained normal at the most recent
      follow-up, 15 months after initiation of rituximab. Children with MuSK
      myasthenia, like adults, can respond to rituximab despite long standing disease
      and failure to improve on other immunosuppressant medications. 

PMID- 25998612
TI  - 208th ENMC International Workshop: Formation of a European Network to develop a
      European data sharing model and treatment guidelines for Pompe disease Naarden,
      The Netherlands, 26-28 September 2014.

PMID- 25998613
TI  - Convenient synthesis of phosphonodipeptides containing C-terminal alpha
      aminoalkylphosphonic acids.
AB  - Phosphonopeptides are important phosphorus analogs of natural peptides and have
      been widely applied as enzyme inhibitors and antibacterial agents. A series of
      phosphonodipeptides containing C-terminal alpha-aminoalkylphosphonic acids was
      synthesized in satisfactory to good yields conveniently from 2-(N
      benzyloxycarbonylamino)alkanamides, aldehydes, and phosphorus trichloride via
      Mannich-type reaction and subsequent sequential hydrolysis. The reaction
      mechanism was proposed and verified by (31)P NMR tracing experiments. The current
      method is an efficient and convenient method for preparation of phosphonopeptides
      containing C-terminal alpha-aminoalkylphosphonic acids.

PMID- 25998614
TI  - Infection control challenges of infrequent and rare fungal pathogens: lessons
      from disseminated Fusarium and Kodamaea ohmeri infections.

PMID- 25998615
TI  - Polymyxin B hemoperfusion in sepsis: growing body of evidence and occasional
      conflicting results.

PMID- 25998616
TI  - Virulence factors and mechanisms of antimicrobial resistance in Shigella strains
      from periurban areas of Lima (Peru).
AB  - The study was aimed to describe the serotype, mechanisms of antimicrobial
      resistance, and virulence determinants in Shigella spp. isolated from Peruvian
      children. Eighty three Shigella spp. were serogrouped and serotyped being
      established the antibiotic susceptibility. The presence of 12 virulence factors
      (VF) and integrase 1 and 2, along with commonly found antibiotic resistance genes
      was established by PCR. S. flexneri was the most relevant serogroup (55 isolates,
      66%), with serotype 2a most frequently detected (27 of 55, 49%), followed by S.
      boydii and S. sonnei at 12 isolates each (14%) and S. dysenteriae (four isolates,
      5%). Fifty isolates (60%) were multi-drug resistant (MDR) including 100% of S.
      sonnei and 64% of S. flexneri. Resistance levels were high to trimethoprim
      sulfamethoxazole (86%), tetracycline (74%), ampicillin (67%), and chloramphenicol
      (65%). Six isolates showed decreased azithromycin susceptibility. No isolate was
      resistant to nalidixic acid, ciprofloxacin, nitrofurantoin, or ceftriaxone. The
      most frequent resistance genes were sul2 (95%), tet(B) (92%), cat (80%), dfrA1
      (47%), blaOXA-1like (40%), with intl1 and intl2 detected in 51 and 52% of the
      isolates, respectively. Thirty-one different VF profiles were observed, being the
      ipaH (100%), sen (77%), virA and icsA (75%) genes the most frequently found.
      Differences in the prevalence of VF were observed between species with S.
      flexneri isolates, particularly serotype 2a, possessing high numbers of VF. In
      conclusion, this study highlights the high heterogeneity of Shigella VF and
      resistance genes, and prevalence of MDR organisms within this geographic region. 

PMID- 25998617
TI  - Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and
      differentially modulate apoptosis in breast cancer.
AB  - BACKGROUND: Iron binding, naturally occurring protein bovine lactoferrin (bLf)
      has attracted attention as a safe anti-cancer agent capable of inducing
      apoptosis. Naturally, bLf exists partially saturated (15-20%) with Fe(3+)
      however, it has been demonstrated that manipulating the saturation state can
      enhance bLf's anti-cancer activities. METHODS: Apo-bLf (Fe(3+) free) and Fe-bLf
      (>90% Fe(3+) Saturated) were therefore, tested in MDA-MB-231 and MCF-7 human
      breast cancer cells in terms of cytotoxicity, proliferation, migration and
      invasion. Annexin-V Fluos staining was also employed in addition to apoptotic
      protein arrays and Western blotting to determine the specific mechanism of bLf
      induced apoptosis with a key focus on p53 and inhibitor of apoptosis proteins
      (IAP), specifically survivin. RESULTS: Apo-bLf induced significantly greater
      cytotoxicity and reduction in cell proliferation in both cancer cells showing a
      time and dose dependent effect. Importantly, no cytotoxicity was detected in
      normal MCF-10-2A cells. Both forms of bLf significantly reduced cell invasion in
      cancer cells. Key apoptotic molecules including p53, Bcl-2 family proteins, IAP
      members and their inhibitors were significantly modulated by both forms of bLf,
      though differentially in each cell line. Most interestingly, both Apo-bLf and Fe
      bLf completely inhibited the expression of survivin protein (key IAP), after 48 h
      at 30 and 40 nM in cancer cells. CONCLUSIONS: The capacity of these forms of bLf
      to target survivin expression and modulation of apoptosis demonstrates an
      exciting potential for bLf as an anti-cancer therapeutic in the existing void of
      survivin inhibitors, with a lack of successful inhibitors in the clinical
      management of cancer.

PMID- 25998618
TI  - Neonatal jaundice: phototherapy.
AB  - INTRODUCTION: About 50% of term and 80% of preterm babies develop jaundice, which
      usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2
      weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in
      newborn infants is a result of increased red cell breakdown and decreased
      bilirubin excretion. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical questions: What are the effects of
      different wavelengths of light in hospital phototherapy as treatment for
      unconjugated hyperbilirubinaemia in term and preterm infants? What are the
      effects of different intensities of light in hospital phototherapy as treatment
      for unconjugated hyperbilirubinaemia in term and preterm infants? What are the
      effects of different total doses of light in hospital phototherapy as treatment
      for unconjugated hyperbilirubinaemia in term and preterm infants? What are the
      effects of starting hospital phototherapy at different thresholds in term and
      preterm infants? We searched Medline, Embase, The Cochrane Library, and other
      important databases up to January 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: Fourteen studies were included. 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 different wavelengths, intensities, total doses, and threshold for
      commencement of the following intervention: hospital phototherapy.

PMID- 25998619
TI  - Ex Vivo Culture of CTCs: An Emerging Resource to Guide Cancer Therapy.
AB  - With increasing application of targeted therapies and the development of acquired
      resistance, much attention is being focused on developing in vitro and in vivo
      patient-specific tumor models for individualized therapeutic evaluation of
      cancers. Circulating tumor cells provide a source of noninvasively and
      sequentially sampled invasive cancer cells suitable for propagation in vitro. We
      review the advantages and challenges associated with ex vivo culture of tumor
      cells circulating in the blood of patients with cancer.

PMID- 25998621
TI  - Signaling through RIG-I and type I interferon receptor: Immune activation by
      Newcastle disease virus in man versus immune evasion by Ebola virus (Review).
AB  - In this review, two types of RNA viruses are compared with regard to the type I
      interferon (IFN) response in order to obtain a better understanding of the
      molecular mechanisms of immune activation or evasion. Upon human infection, both
      viruses exert either beneficial or detrimental effects. The Newcastle disease
      virus (NDV), is a type strain for avian paramyxoviruses, while the Ebola virus
      (EBOV), is a virus affecting primates. During evolution, both viruses
      specifically adapted to their respective hosts, acquiring sophisticated viral
      escape mechanisms. Two types of receptors play an important role in the life
      cycle of these two viruses: cytoplasmic retinoic acid-inducible gene I (RIG-I)
      and membrane expressed type I IFN receptor (IFNAR). In mouse and human cells, NDV
      is a strong inducer of the type I IFN response. The early phase of this is
      initiated by signaling through RIG-I and the late response by signaling through
      IFNAR. EBOV does not induce type I IFN responses in humans as it has viral
      proteins that specifically and strongly interfere with RIG-I and IFNAR signaling,
      as well as immune activation. In this review, we discuss whether the beneficial
      effects of one virus can be exploited in the fight against the detrimental
      effects of the other.

PMID- 25998620
TI  - The Role of TLR4 in Chemotherapy-Driven Metastasis.
AB  - Tumor resistance to cytotoxic drugs is one of the main obstacles to successful
      cancer therapy. Emerging evidence suggests that chemoresistance is promoted by
      substances released from dead and damaged cells that activate the host repair
      program orchestrated by Toll-like receptor-4 (TLR4). TLR4 is often overexpressed
      in malignant and tumor-infiltrating immune cells. In addition to endogenous
      ligands released by therapy-induced tumor destruction, TLR4 is directly activated
      by paclitaxel, one of the most commonly used chemotherapeutic drugs against
      various human cancers. TLR4 activation promotes local and systemic inflammation,
      leading to induction of multiple circuits that create a regenerative environment
      favoring local recurrence and metastasis. Of particular importance is TLR4
      mediated recruitment of endothelial progenitors derived from immature myeloid
      cells. These cells play a major role in rebuilding tumor-associated lymphatic and
      blood vessels, thereby promoting lymphatic and hematogenous metastasis. The
      latter is further enhanced by the premetastatic niche generated by mobilization
      of myeloid provascular cells to distant organs. This review summarizes the recent
      evidence demonstrating that paclitaxel and other clinically used anticancer drugs
      actively induce metastasis even while shrinking the primary tumor. Better
      understanding of the mechanisms underlying TLR4-dependent chemotherapy-driven
      metastasis might be the key to overcoming challenges of cancer eradication.

PMID- 25998622
TI  - The design of a spiro-pyrrolidine organocatalyst and its application to catalytic
      asymmetric Michael addition for the construction of all-carbon quaternary
      centers.
AB  - A novel chiral spiro-pyrrolidine silyl ether organocatalyst has been designed.
      Its catalytic asymmetric effect is demonstrated by the Michael addition reaction,
      which affords the desired products with an all-carbon quaternary center in up to
      99% ee and 87% yield. Furthermore, the reaction process has been investigated via
      in situ NMR experiments. 

PMID- 25998623
TI  - Depressive symptom severity, contributing factors, and self-management among
      chronic dialysis patients.
AB  - Despite the high prevalence of depressive symptoms in patients receiving chronic
      dialysis, there has been inadequate attention to patient-related barriers to
      management of depressive symptoms, such as factors identified by these patients
      as contributing to their symptoms, and how they responded to the symptoms.
      Participants (N = 210) in an ongoing longitudinal observational study of
      multidimensional quality of life in patients receiving chronic dialysis completed
      a battery of measures monthly for 12 months. For each patient at each measurement
      point, an event report was generated if he or she scored outside of the normal
      range on the depressive symptom scale (Center for Epidemiologic Studies
      Depression Scale-Short Form [CESD-SF] >=10) or expressed suicidal ideation. Of
      the 210 participants, 100 (47.6%) had a CESD-SF score >=10 at least once
      resulting in 290 event reports. Of these 100 participants, 15 (15%) had also
      reported suicidal ideation in addition to having depressive symptoms. The most
      frequently stated contributing factors included "managing comorbid conditions and
      complications" (56 event reports, 19.3%), "being on dialysis" (50, 17.2%),
      "family or other personal issues" (37, 12.8%), and "financial difficulties" (31,
      10.7%). On 11 event reports (3.8%) participants had been unaware of their
      depressive symptoms. On 119 event reports (41%) participants reported that they
      discussed these symptoms with their dialysis care providers or primary care
      providers, while on 171 event reports (59%) symptoms were not discussed with
      their health-care providers. The prevalence of depressive symptoms is high and
      many patients lack knowledge about effective self-management strategies. 

PMID- 25998624
TI  - Comparison of rivaroxaban and parnaparin for preventing venous thromboembolism
      after lumbar spine surgery.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of
      rivaroxaban for preventing venous thromboembolism (VTE) after lumbar spine
      surgery. METHODS: In this randomized, controlled study, 665 patients who
      underwent lumbar surgery were randomly assigned to receive either rivaroxaban or
      parnaparin. Rivaroxaban and parnaparin were used for preventing postoperative
      venous thrombosis. The occurrence of postoperative efficacy endpoint events
      (venous thrombosis) and safety endpoint events (hemorrhage) was compared for each
      group. RESULTS: Efficacy endpoint results: in the rivaroxaban group, there were 6
      thrombotic events (1.7%), 2 cases with severe VTE (0.6%), and 3 cases with
      symptomatic VTE (0.9%). In the parnaparin group, there were 10 thrombotic events
      (3.1%), 4 cases with severe VTE (1.2%), and 6 cases with symptomatic VTE (1.9%).
      Safety endpoint results: in the rivaroxaban group, there were 21 cases with
      bleeding events (6.2%), 2 cases with severe bleeding (0.6%), and 19 cases with
      non-severe bleeding (5.6%). In the parnaparin group, there were 21 bleeding
      events (6.2%), 1 case with severe bleeding (0.3%), and 16 cases with non-severe
      bleeding (4.9%). The incidences of thromboembolic events, including severe and
      symptomatic VTE, were not significantly different between the two groups (P >
      0.05). Bleeding event rates, including severe and non-severe bleeding, were also
      not significantly different. CONCLUSIONS: Rivaroxaban proved to be equally
      effective as parnaparin for anticoagulation therapy, with both drugs exhibiting a
      similar prevention effect against postoperative VTE after lumbar spine surgery,
      without increasing the risk of postoperative bleeding.

PMID- 25998625
TI  - Effect of blood-sugar limitation on intensive care mortality: Intragroup
      evaluation.
AB  - OBJECTIVE: To evaluate the safety profile of blood sugar limits in intensive care
      unit (ICU) patients. METHODS: Adult patients with ICU stay >36 h, more than two
      blood sugar measurements and antibiotic therapy concordant with locally adapted
      guidelines were included. For analyses, one study cohort was defined in two ways:
      as a narrow group, euglycaemic patients' blood sugar levels 80-150 mg/dl; as a
      moderate group, euglycaemic patients' blood sugar levels 80-180 mg/dl.
      Dysglycaemia was defined as blood sugar levels <80 mg/dl for >5% of measurements,
      and >150 mg/dl or >180 mg/dl (narrow or moderate groups, respectively) for >10%
      of measurements. The primary endpoint was ICU mortality (euglycaemia versus
      dysglycaemia). RESULTS: The study comprised 668 patients. When defined as a
      narrow group, ICU mortality was 3% (four of 135) euglycaemic versus 10% (54/533)
      dysglycaemic patients (odds ratio [OR] 3.692, 95% confidence interval [CI] 1.313,
      10.382). When defined as a moderate group, ICU mortality was 6% (21/351)
      euglycaemic versus 12% (37/317) dysglycaemic patients (OR 2.077, 95% CI 1.188,
      3.630). Frequency of severe hypoglycaemia (blood sugar <40 mg/dl) was not
      different between the narrow and moderate euglycaemic ranges. CONCLUSIONS:
      Euglycaemia was associated with lower ICU mortality than dysglycaemia, and
      incidence of hypoglycaemia was low overall in this study. Based on current
      published evidence, therapeutic targets should be defined according to individual
      patient characteristics.

PMID- 25998626
TI  - Relationship between dietary pattern and cognitive function in elderly patients
      with type 2 diabetes mellitus.
AB  - OBJECTIVE: To analyse the relationships between dietary patterns and cognitive
      function in elderly patients with type 2 diabetes mellitus (T2DM). METHODS:
      Patients with T2DM completed a 3-day dietary record and Mini-mental State
      Examination (MMSE). Dietary patterns were identified by factor analysis. RESULTS:
      The study included 73 patients and identified five dietary patterns, one of which
      was characterized by high loading for vegetables and fish. A higher consumption
      of vegetables and fish was significantly associated with improved MMSE score
      (unadjusted model, model adjusted for age and sex, and model adjusted for age,
      sex, education, diabetic nephropathy and alcohol consumption), and decreased
      prevalence of suspected mild dementia (unadjusted model, model adjusted for age
      and sex). CONCLUSIONS: A high score in the vegetables and fish dietary pattern
      was associated with high MMSE score and low prevalence of suspected mild dementia
      in elderly patients with T2DM.

PMID- 25998627
TI  - Mummies are Alive... Within the Pages of The Anatomical Record!

PMID- 25998628
TI  - Unwrapping the anatomy of mummies.

PMID- 25998630
TI  - Impact: development of a radiological mummy database.
AB  - The Internet Mummy Picture Archiving and Communication Technology (IMPACT)
      radiological and context database, is a large-scale, multi-institutional,
      collaborative research project devoted to the digital preservation and scientific
      study of mummified remains, and the mummification traditions that produced them,
      using non-destructive medical imaging technologies. Owing to the importance of
      non-destructive analyses to the study of mummified human remains, the IMPACT
      database, website, and wiki provide a basis for anthropological and
      palaeopathological investigations, grounded in the most current technological
      imaging and communication standards, accessible through any internet connection,
      and protected against rapidly changing media standards. Composed of paired online
      radiographic and contextual databases, the IMPACT project is intended to provide
      researchers with large-scale primary data samples for anthropological and
      palaeopathological investigations. IMPACT addresses the limitations of the case
      study approach to mummified human remains and contributes to the development of
      standards of practice in imaging of mummified remains. Furthermore, IMPACT allows
      researchers a greater appreciation of, and engagement with, patterns of health
      and disease in ancient times as well as the variability present in the
      mummification traditions of ancient Egypt and other cultures that sought to
      preserve their dead for eternity.

PMID- 25998629
TI  - The anatomy of the mummy: mortui viventes docent--when ancient mummies speak to
      modern doctors.
AB  - There is almost a universal fascination with prehistoric, protohistoric, and
      historic human remains that preserve the soft tissues (nonskeletal) of the body
      (general definition of a mummy). While most people within the general public
      engage with mummies as part of a museum exhibit process, many scientists have
      taken that fascination much further. Starting as a general fascination with
      mummification, the scientific process involved in the study of mummies began in
      earnest in the late 18th Century AD. This issue of the Anatomical Record was
      conceived and formulated to bring together a series of researchers to highlight
      their most groundbreaking research on the scientific advances that surround the
      21st Century AD study of these preserved biological beings including an
      illumination of the cultural processes that purposefully or inadvertently are
      preserved either within their tissues or are present within the context
      (archaeological) in which they are found (excavated). Twenty-six research
      articles are presented in this volume on a variety of topics all related to the
      rich transdisciplinary fields that are now directing their research efforts to
      the state-of-the art analysis of human mummified remains.

PMID- 25998631
TI  - PUM I Revisited: Tradeoffs in Preservation and Discovery.
AB  - An Egyptian mummy designated PUM I (Pennsylvania University Museum) was subjected
      to a complete autopsy in 1972. Forty-one years later, the senior author (MZ) was
      invited back to the Penn Museum to identify several packages of material that had
      been preserved with the mummy joining the project conservator (MG) in the
      evaluation of these remains. A summary of the 1972 examination reviews the dating
      of the mummy, about 3,000 years ago. The mummy was poorly preserved and the only
      significant pathology was a rare skin disease, subcorneal pustular dermatosis,
      which was not identified by modern medicine until 1956. The review of PUM 1, as
      the mummy is stabilized during conservation at the Penn Museum (previously called
      the Pennsylvania University Museum), generates a discussion for researchers who
      embark on the study of mummified remains. There have been major advances in the
      study of mummies since 1972, including computed tomography (CT) scanning, with
      much less invasive endoscopically guided biopsies, analysis for ancient DNA
      (aDNA), nuclear magnetic resonance technology, chemical analysis, and
      paleoserology. The value of complete autopsy must now be balanced against
      preservation of a complete mummy by less invasive techniques that are tissue
      sampled through guided technology. Indeed it is unlikely that these regions of
      the skin of PUM 1 would have been sampled and studied if these new tools of
      analysis had been available and applied.

PMID- 25998632
TI  - Modeling ancient Egyptian mummification on fresh human tissue: macroscopic and
      histological aspects.
AB  - Many studies have been concerned with the ancient Egyptian mummification method;
      nevertheless, little effort has been made to explore it experimentally. The goal
      of this study is to apply evidence-based diagnostic criteria and state-of-the art
      methodology in order to improve knowledge on soft tissues preservation and
      postmortem alterations. Two human lower limbs (LL) from a female donor were (1)
      "naturally" mummified by dry heat and (2) artificially in natron. At specific
      time intervals a macroscopic and radiological examination of the LL was performed
      and skin and muscle samples were taken for histological and biomolecular
      analysis. Temperature, humidity, pH, and weight of the LL were systematically
      measured. The mummification by dry heat was stopped after 7 days due to
      unexpected lack of mummification progress. The mummification in natron was
      completed successfully after 208 days. The humidity, the external temperature,
      and the pH were proven with Pearson correlation and principal component analysis
      as important factors for the mummification process. The steady removal of water
      from the tissues through the natron has prevented the putrefaction. This is also
      evident in the absence of bacteria or fungi through the microbiological analysis.
      The histological analysis revealed very good preservation of the skin and the
      muscle tissues. In the muscular sample certain degree of structural
      disintegration can be seen, particularly affecting the epimysium whilst in the
      skin samples the epidermis, especially the stratum corneum, is mostly affected.
      The samples show better preservation compared with ancient Egyptian sections and
      other mummified tissues from historic or forensic context.

PMID- 25998633
TI  - Paleoradiology of the Savoca Mummies, Sicily, Italy (18th-19th Centuries AD).
AB  - Mummified remains have been successfully studied radiologically since the end of
      the 19th century, giving rise to a specific field of research-paleoradiology. In
      this paper, we present the results of the first radiological investigation of a
      collection of Sicilian mummies found in a subterranean chamber beneath the
      Capuchin Church of Savoca. The chamber contains a number of preserved bodies,
      either held in special niches in the walls or interred within coffins. A recent
      detailed radiological examination of these mummies allowed the authors to
      determine information relating to the funerary treatment and some of the
      pathological alterations witnessed in the remains. Specifically, evidence of gout
      and DISH was identified, along with frequent degenerative joint disease,
      suggestive of rich dietary habits and a longer life expectancy. These findings
      were interpreted in the light of historical information and the social status of
      the subjects concerned.

PMID- 25998634
TI  - The Thule Inuit Mummies From Greenland.
AB  - Fourteen Thule Culture Inuit mummies are described here, including remarks on the
      cultural and archaeological setting of the Thule people. The mummy finds pertain
      to two mummy caches: six mummies found near Nuuk, at the site Pissisarfik, and
      eight mummies from Qilakitsoq. The latter find is the biggest mummy find in the
      Arctic. The mummies are all children and females. Although their state of
      preservation is uneven, much data about the Thule culture people has been gleaned
      from them. This includes the use of facial tattooing, Paleopathology and isotopic
      and genetic data.

PMID- 25998635
TI  - Bog bodies.
AB  - In northern Europe during the Iron Age, many corpses were deposited in bogs. The
      cold, wet and anaerobic environment leads in many cases to the preservation of
      soft tissues, so that the bodies, when found and excavated several thousand years
      later, are remarkably intact. Since the 19th century the bog bodies have been
      studied using medical and natural scientific methods, and recently many bog
      bodies have been re-examined using especially modern, medical imaging techniques.
      Because of the preservation of soft tissue, especially the skin, it has been
      possible to determine lesions and trauma. Conversely, the preservation of bones
      is less good, as the mineral component has been leached out by the acidic bog.
      Together with water-logging of collagenous tissue, this means that if the bog
      body is simply left to dry out when found, as was the case pre-19th century, the
      bones may literally warp and shrink, leading to potential pitfalls in
      paleopathological diagnostics. Bog bodies have in several instances been crucial
      in determining the last meal, as gut contents may be preserved, and thus augment
      our knowledge on pre-historic diet by adding to, for example, stable isotope
      analyses. This article presents an overview of our knowledge about the taphomic
      processes as well as the methods used in bog body research.

PMID- 25998636
TI  - Mummy Restoration Project Among the Anga of Papua New Guinea.
AB  - We report on a unique Mummy restoration project among the anga of papua new
      guinea. Moimango was a village leader who had gone through the smoked body
      mummification process about 50 years ago. His smoked body has been displayed,
      alongside other ancestors, on a cliff niche gallery 308 m (1011 feet) above Koke
      Village. Although somewhat protected by an overhang, Moimango suffered a great
      deal of deterioration as he has been unprotected and exposed to the elements. The
      goals of our 2010 expedition to Koke Village was to assess the efficacy of
      restoration efforts applied to Moimango initiated by the authors and villagers of
      Koke in 2008. The restoration process used materials native to the local jungles.
      We examined Moimango for additional restoration challenges that may have arisen
      since the 2008 expedition. We discovered that many of the restoration techniques
      developed and applied in 2008 held up well. We found that the anatomical supports
      developed from native tapa and kumaka sap were still in place and effective, as
      well as our lichen eradication method of a suca slurry applied in 2008. Of
      particular importance was the stability of Moimago's head, which prior to
      restoration, was held in place by only the mummified muscle and integument of the
      lateral and posterior neck region. Endoscopic evaluation demonstrated
      disarticulated C1 and C2 vertebrae. New restoration challenges included
      construction of a new display chair, realignment and securing of the mandible,
      replacing and securing a loose tooth, repatching, and recoating with ritualistic
      red ochre clay.

PMID- 25998637
TI  - The Tres Ventanas Mummies of Peru.
AB  - The Tres Ventanas mummies of Peru are thought to be among the oldest mummies in
      existence, dating to between 8,000 and 10,000 years ago. A preliminary assessment
      is made of the potential of these mummies for use in future research on mummified
      remains. Although the Tres Ventanas cave and the four mummies were explored and
      then excavated by Frederic Engel in 1966-67, and the project is named in his
      honor as the "Engel Study Group", the importance of both the physical remains and
      the context in which they were found has only come to light in the last few
      years. Most important is the paleopathological examination of these remains,
      since these mummies are found in a high altitude area of Peru where adaptation to
      the limited partial pressure of oxygen is perhaps a key component in broadening
      our understanding of human diversity in past populations.

PMID- 25998638
TI  - The orthopedic diseases of ancient Egypt.
AB  - BACKGROUND: CT scanning of ancient human remains has the potential to provide
      insights into health and diseases. While Egyptian mummies have undergone CT scans
      in prior studies, a systematic survey of the orthopedic conditions afflicting a
      group of these ancient individuals has never been carried out. METHODS: We
      performed whole body CT scanning on 52 ancient Egyptian mummies using technique
      comparable to that of medical imaging. All of the large joints and the spine were
      systematically examined and osteoarthritic (OA) changes were scored 0-4 using
      Kellgren and Lawrence classification. RESULTS: The cruciate ligaments and menisci
      could be identified frequently. There were much more frequent OA changes in the
      spine (25 mummies) than in the large joints (15 cases of acromioclavicular and/or
      glenohumeral joint OA changes, five involvement of the ankle, one in the elbow,
      four in the knee, and one in the hip). There were six cases of scoliosis.
      Individual mummies had the following conditions: juvenile aseptic necrosis of the
      hip (Perthes disease), stage 4 osteochondritis dissecans of the knee, vertebral
      compression fracture, lateral patella-femoral joint hyper-compression syndrome,
      severe rotator cuff arthropathy, rotator cuff impingement, hip pincer
      impingement, and combined fracture of the greater trochantor and vertebral bodies
      indicating obvious traumatic injury. This report includes the most ancient
      discovery of several of these syndromes. CONCLUSIONS: Ancient Egyptians often
      suffered painful orthopedic conditions. The high frequency of scoliosis merits
      further study. The pattern of degenerative changes in the spine and joints may
      offer insights into activity levels of these people.

PMID- 25998639
TI  - A radiologic study of an ancient Egyptian mummy with a prosthetic toe.
AB  - A radiologic examination (both CT and traditional X-ray) of two mummies curated
      at the Albany Institute of History and Art revealed the identity of the mummified
      remains as well as details of the person's life style parameters (markers of
      occupational stress). These mummies, brought to the Institute over 100 years ago,
      were unstudied until 1989. This preliminary study led to the misappropriation of
      the remains, and subsequent switching of the remains within their coffins. Recent
      and more detailed analyses lead to the correct identification of sex, a re
      association of the remains to their interment coffins, as well as a detailed
      analysis of occupational markers. A prosthetic toe was identified in one of the
      mummies which lead to the functional exploration of prosthetics in the past
      including their use as part of funerary processing in ancient Egypt. Finally,
      details of the embalming process place the wrapped mummy within the time frame
      identified on the coffin of the mummy identified as Ankhefenmut as well as
      confirming his social status.

PMID- 25998640
TI  - Histology of a Woolly Mammoth (Mammuthus primigenius) Preserved in Permafrost,
      Yamal Peninsula, Northwest Siberia.
AB  - In 2007, the baby woolly mammoth (Mammuthus primigenius) named Lyuba was found
      frozen in the Siberian tundra permafrost along the Yuribey River. She was
      proclaimed the best-preserved mammoth discovery. As part of the endoscopic
      examination of Lyuba, tissue samples of hair, muscle, and internal organs were
      taken. The sectioned biopsies were stained using standard and special
      histological stains. In general, the microscopic preservation of the tissue was
      good although no clearly identifiable cell nuclei were found by standard staining
      methods. Only a few cell nuclei could be identified in some samples when
      fluorescence stained with DAPI. The best-preserved structures were collagen
      fibers and muscle tissue, which gave some structural resemblance to the organs.
      In the hairs, evidence of pigmentation, a scaly surface, diagonal intra-hair
      structures, and a medulla were seen. Fat droplets could be identified with Sudan
      Red in the subcutaneous fat sample and in several organs. Bacteria were seen on
      the lumen side of the small intestine and caecum, and in the liver and lung
      tissue. In addition, fungi and pollen were seen in the lung sample. In the wall
      of the caecum and small intestine, blood vessels and nerves were visualized. Iron
      was identified in the vivianite sample. Some biopsies compared well structurally
      with the African elephant tissue sections. The histological findings support the
      theory that Lyuba drowned in muddy water. The microscopic tissue preservation and
      cell nuclei destruction indicate that Lyuba's body underwent at least one freeze
      thaw cycle.

PMID- 25998641
TI  - CT Examination of Nose and Paranasal Sinuses of Egyptian Mummies and Three
      Distinct Human Population Groups: Anthropological and Clinical Implications.
AB  - The interaction of nasal morphology and climatic conditions has resulted in
      diverse hard- and soft-tissue configurations across human population groups.
      While the processes of skull pneumatization are not fully understood, the
      invasions of the paranasal sinuses [PNS] into the cranium have contributed to
      assorted morphologies. Human migratory patterns and the strong association with
      climatic variables through time and space may explain this diversity. This study
      examined four multiregional populations of which two are from Egypt but of widely
      divergent eras. Three Egyptian mummies [EG-M] from the middle kingdom were CT
      scanned providing a unique opportunity to investigate the status of PNS anatomy
      within a time frame from 1567 BCE to 600 CE and compare it to a contemporary
      Egyptian [EG] (n = 12) population. Dry skulls of Inuit [IT] (n = 10) and East
      African [EA] (n = 8) provide out-group comparisons, as one group represents an
      isolated geographic environment far different from that of Egypt and the other
      group inhabiting distinct environmental conditions albeit located within the same
      continent. Results showed EG-M and EG frontal sinus volumes were diminutive in
      size with no statistically significant difference between them. Maxillary sinus
      size values of EG-M and EG clustered together while IT and EA significantly
      differed from each other (P = 0.002). The multiregional groups exhibited
      population specific morphologies in their PNS anatomy. Ecogeographic localities
      revealed anatomical differences among IT and EA, while the potential time span of
      about 3,500 years produced only a negligible difference between the Egyptian
      groups. The small sample sizes incorporated into this research requires
      confirmation of the results by analyses of larger samples from each geographic
      region and with the integration of a larger group of Egyptian mummified remains.

PMID- 25998642
TI  - Short Review: The Use of Conventional X-rays in Mummy Studies.
AB  - X-raying is arguably the most well-known, non-invasive technique for visualising
      the internal structures of ancient mummies and bog bodies. There are several
      factors such as the easy availability, the relative cheapness as well as the high
      spatial resolution, which speaks for this diagnostic modality in ancient mummy
      research. The aim of this short review is to address the advantages and pitfalls
      of this particular technique for such unique samples. We recommend that when
      results of X-ray examination of mummies are presented, the specific recording
      data should be listed, and any given finds, for example, of Paleopathology,
      should be cross-checked against other sources, for example, CT-scanning, direct
      inspection (also by endoscopy), and so forth.

PMID- 25998643
TI  - Considered limitations and possible applications of computed tomography in mummy
      research.
AB  - Over the past two decades, computed tomography, CT, has become one of the most
      significant imaging modalities in clinical medicine. The hardware and software
      innovations responsible for the advances in image quality have also resulted in
      the desire to incorporate CT into mummy research. Although manufacturers have
      endeavored to simplify the operation of the equipment, the intended use has been
      primarily living humans and not dehydrated remains. However, with a thorough
      understanding of the underlying principles of the modality, including the
      limitations, and the consequences of the manipulation of technical settings,
      satisfactory results can be obtained.

PMID- 25998644
TI  - A Critical Look at Mummy CT Scanning.
AB  - Computed tomography scanning of mummies has been conducted for almost 40 years,
      and has become an increasingly popular method of mummy study in the 21st century.
      However, most CT scan analyses published today still do little more than praise
      the technique's non-destructive, non-invasive properties. Despite the wealth of
      information contained within a modern, high definition scan, most researchers
      have yet to fully exploit the full potential of this technology. In addition,
      those that have utilized CT scanning in ancient remains continue to interpret
      mummified tissues as though they were living, without investigating how taphonomy
      and mummification could have effected the tissue images that are produced.
      Because of this, there is very limited information available for clear
      interpretation of mummy CT's. This article presents a critical assessment of the
      development of mummy CT scanning and presents the results of two Egyptian mummies
      CT'ed at the Penn Museum as an example of the potentials and pitfalls of high
      resolution scanning.

PMID- 25998645
TI  - Short Review: Magnetic Resonance Imaging of Ancient Mummies.
AB  - Noninvasive imaging of ancient tissues is of increasing interest in
      palaeopathological studies, with conventional X-ray and computed tomography
      currently considered the diagnostic gold standard. Convenitional X-ray has a long
      tradition, yet imaging of ancient mummies using conventional X-ray technique has
      its drawbacks too. Until recently, magnetic resonance imaging (MRI) of soft
      tissues was successful with ancient dry tissues only after morphology-altering
      rehydration. This process was deemed necessary due to the previous reported lack
      of unbound protons. Hitherto, any approach without rehydration of the historic
      samples failed. Yet, the successful application of novel MRI techniques allows
      broadening of the methodological spectrum of methods for noninvasive studies on
      ancient corpses, whether they have wet or dry soft tissue, or bone. Spatial
      discrimination of chemical elements can now be carried out with high sensitivity
      in any historic specimen, leading to an increased level of diagnostic evidence.

PMID- 25998646
TI  - Application and limitations of endoscopy in anthropological and archaeological
      research.
AB  - The use of endoscopy in anthropological and archaeological research was been well
      documented in the literature. This article explores the varied settings in which
      endoscopy is beneficial in gathering visual data for interpretation related to
      cultural remains and artifacts. Endoscopic data may be used to assist in the
      pursuit of answering such bioanthropological questions as sex, age at death,
      presence of paleopathologies, dental conditions, and cultural practices.
      Endoscopy is often used to guide and document biopsy procedures as well as the
      retrieval of artifacts from within poorly accessible locations such as body
      cavities, coffins, or tombs. In addition, endoscopic data is used to examine such
      archaeological features as tomb structure and design. A contrast between the
      medical and anthropological approach is described. Endoscopic research is
      enhanced when applied in conjunction with additional varied imaging modalities.
      While invasive, endoscopy is a nondestructive methodological approach. As with
      all methods, endoscopy has application and interpretational limitations, which
      can be described as limitations resulting from instrumentation, and those arising
      from personnel less familiar with the various approaches to endoscopy in both
      field and laboratory settings.

PMID- 25998647
TI  - Terahertz imaging modalities of ancient Egyptian mummified objects and of a
      naturally mummified rat.
AB  - During the last few years, terahertz (THz) imaging has been used to investigate
      artwork and historic artifacts. The application of THz imaging to mummy
      investigations is very attractive since it provides spectroscopic information
      over a broad frequency range and its radiation has proven to be harmless to human
      cells. However, compared with the current standard imaging methods in mummy
      imaging-X-ray and computed tomography (CT)--it remains a novel, emerging
      technique whose potential still needs to be fully evaluated. Here, ancient
      Egyptian mummified objects as well as a naturally mummified rat have been
      investigated by two different THz imaging systems: a broadband THz time domain
      imaging system and an electronic THz scanner. The obtained THz images are
      compared with conventional CT, X-ray, and magnetic resonance images. While the
      broadband THz time domain setup permits analyses of smaller samples, the
      electronic THz scanner allows the recording of data of thicker and larger samples
      at the expense of a limited spectral bandwidth. Terahertz imaging shows clear
      potential for mummy investigations, although currently CT imaging offers much
      higher spatial resolution. Furthermore, as commercial mobile THz scanners become
      available, THz imaging could be applied directly in museums or at excavation
      sites.

PMID- 25998648
TI  - Revealing the face of an ancient Egyptian: synthesis of current and traditional
      approaches to evidence-based facial approximation.
AB  - The technique of forensic facial approximation, or reconstruction, is one of many
      facets of the field of mummy studies. Although far from a rigorous scientific
      technique, evidence-based visualization of antemortem appearance may supplement
      radiological, chemical, histological, and epidemiological studies of ancient
      remains. Published guidelines exist for creating facial approximations, but few
      approximations are published with documentation of the specific process and
      references used. Additionally, significant new research has taken place in recent
      years which helps define best practices in the field. This case study records the
      facial approximation of a 3,000-year-old ancient Egyptian woman using medical
      imaging data and the digital sculpting program, ZBrush. It represents a synthesis
      of current published techniques based on the most solid anatomical and/or
      statistical evidence. Through this study, it was found that although certain
      improvements have been made in developing repeatable, evidence-based guidelines
      for facial approximation, there are many proposed methods still awaiting
      confirmation from comprehensive studies. This study attempts to assist artists,
      anthropologists, and forensic investigators working in facial approximation by
      presenting the recommended methods in a chronological and usable format.

PMID- 25998649
TI  - CT-Based Assessment of Relative Soft-Tissue Alteration in Different Types of
      Ancient Mummies.
AB  - Mummification leads to alteration of soft-tissue morphology. No research has
      focused specifically on differences in soft-tissue shrinkage depending on
      mummification type. This study evaluated whether soft-tissue alteration is
      dependent on type of mummification. A total of 17 human mummies have been
      investigated by computed tomography (CT). Samples included artificially embalmed
      ancient Egyptian mummies, naturally mummified South American corpses, ice mummies
      (including the Iceman, South Tyrol Museum of Archeology, Bolzano, Italy, ca.
      3,300 BC), bog bodies and a desiccated mummy of possibly Asian provenance. The
      acquired data were compared to four contemporary bodies. The extent of soft
      tissue shrinkage was evaluated using CT data. Shrinkage was defined as soft
      tissue relative to area of bone (in number of voxels). Measurements were taken at
      13 anatomically defined locations. Ice mummies show the highest degree of
      preservation. This finding is most likely explained due to frozen water within
      tissues. All other types of mummies show significantly (at P < 0.05) smaller
      relative area of preserved soft-tissue. Variation between different anatomical
      structures (e.g., upper lip vs. mid-femur) is significant, unlike variation
      within one compartment (e.g., proximal vs. distal humerus). Mummification type
      strongly affects the degree of soft-tissue alteration, surprisingly mostly
      independent of overall historical age. These results highlight the unique
      morphological impact of taphonomy on soft-tissue preservation and are of
      particular interest in tissue research as well as in forensics.

PMID- 25998650
TI  - A code of ethics for evidence-based research with ancient human remains.
AB  - As clinical research constantly advances and the concept of evolution becomes a
      strong and influential part of basic medical research, the absence of a discourse
      that deals with the use of ancient human remains in evidence-based research is
      becoming unbearable. While topics such as exhibition and excavation of human
      remains are established ethical fields of discourse, when faced with
      instrumentalization of ancient human remains for research (i.e., ancient DNA
      extractions for disease marker analyses) the answers from traditional ethics or
      even more practical fields of bio-ethics or more specific biomedical ethics are
      rare to non-existent. The Centre for Evolutionary Medicine at the University of
      Zurich solved their needs for discursive action through the writing of a self
      given code of ethics which was written in dialogue with the researchers at the
      Institute and was published online in Sept. 2011:
      http://evolutionaremedizin.ch/coe/. The philosophico-ethical basis for this a
      code of conduct and ethics and the methods are published in this article.

PMID- 25998651
TI  - Forensic palynological analysis of intestinal contents of a Korean mummy.
AB  - Experimental studies show that pollen resides in the intestinal tract for a
      minimum of seven days to at least 21 days. Because of this long residence time,
      pollen analysis is an important avenue of forensic research. Pollen provides
      evidence of the environment of the decedent as well as foods and medicine. We
      analyzed a coprolite recovered from a Korean mummy. The decedent was a high
      ranking general who lived during the 16th or 17th centuries. Twenty pollen types
      were recovered. These ranged from 100 s to 10,000 s of pollen grains per gram of
      coprolite. Importantly, comparison of the coprolite pollen spectrum to modern
      aeropalynology studies of Korea suggests that the general died in winter between
      middle November to late February. Economic pollen types were most abundant.
      Economic refers to dietary, medicinal, spice, and beverage types. Dietary pollen
      types include pollen from Oryza (rice), Eriogonum (buckwheat), Brassicaceae
      (mustard family), and Solanaceae (tomato-chile pepper family). Pollen consistent
      with dandelion is present and may represent its use as food. Tens of thousands of
      grains from water plants, bur-reed or cattail, dominate the pollen spectrum. We
      believe that this was introduced with water. The large numbers of water-related
      pollen suggest that the general consumed broth, tea, or soup for a considerable
      time before death.

PMID- 25998652
TI  - Joseon funerary texts tested using ancient DNA analysis of a Korean mummy.
AB  - In Korea, ancient DNA (aDNA) analysis has been applied to investigations into the
      genetic affiliations of mummies found in Joseon Dynasty tombs (1392-1910 CE),
      becoming now indispensable tool for researches studying human remains from
      archaeological sites. In the course of our recent examinations on a Korean mummy
      of Joseon Dynasty, we discovered many teeth contained in a pouch. And in fact,
      the historical literature on the topic of Joseon funerals contain general
      accounts of pouches in which an individual's lost teeth were collected over the
      course of a lifetime and, after death, placed in the coffin with the body. To
      test the veracity of the historical texts, the present study undertook aDNA
      analyses and compared the results between specifically questioned (Q) samples
      (teeth) and known (K) samples (brain and bone) from the mummy to ensure that they
      came from the same individual. Although the Q-K comparison of autosomal short
      tandem repeat results did not show full concordance due to allelic drop-outs in
      some loci, our statistical calculation indicated that the teeth in the pouch are
      highly likely those of the mummy. Additionally, Q-K comparison of mitochondrial
      DNA sequence results showed 100% matches between samples. There results, in
      short, could not gainsay the conjecture that the teeth samples originated from
      the person buried in the tomb; and if so, he must have kept his teeth for a long
      time after their loss. As the application of aDNA analysis to Korean mummy
      studies develops, there will be other opportunities to test historical documents,
      particularly those referring to funerary rites.

PMID- 25998653
TI  - "The opening of the mouth"--a new perspective for an ancient Egyptian
      mummification procedure.
AB  - "The opening of the mouth ritual" (OMR) is a central and well-documented
      component of the Ancient Egyptian mortuary ceremony. In the scientific
      literature, we find various references that indicate that parts of this ritual
      correspond to physical opening of the deceased's mouth during its mummification.
      We denote this physical treatment of the dead the "opening of the mouth
      procedure," to underline the distinction against the "opening of the mouth
      ritual," which is performed ceremonially later on the mummy or even the statue.
      The mummifying procedure itself however is known only from rare pictorial
      representations and the later summary descriptions of Greek authors.
      Nevertheless, recently some authors tried, on the basis of paleopathological
      findings, to demonstrate that the mouth of the deceased had to be opened
      physically before mummifying. Careful examination of the mummies of the Swiss
      Mummy Project and other cases reported in the literature showed frequent dental
      pathologies including fractured and totally luxated teeth, which were up to now
      not sufficiently taken into consideration. The detailed report of the preliminary
      procedures of mummifying the Apis bull-as appropriate detailed descriptions for
      humans are missing-gives us insight into the treatment of the oral cavity. Our
      results, when combined with the available historical literature, indicate that
      the OMR can be regarded as a ritualized counterpart of a real "opening of mouth
      procedure" during mummification.

PMID- 25998655
TI  - Detection of alpha-synuclein oligomers in red blood cells as a potential
      biomarker of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      intracellular alpha-synuclein (alpha-syn) deposition. Alterations in alpha-syn
      levels in cerebrospinal fluid (CSF) and plasma of PD patients have been thought
      to be potential PD biomarkers; however, contamination arising from hemolysis
      often influences the accuracy of detecting alpha-syn levels in the CSF and
      plasma. In this study, alpha-syn oligomer levels in red blood cells (RBCs)
      obtained from 100 PD patients, 22 MSA patients, and 102 control subjects were
      measured by enzyme-linked immunosorbent assay. We showed that the ratio of alpha
      syn oligomer/total RBC protein was higher in PD patients than in controls (29.0+/
      19.8 ng/mg vs. 15.4+/-7.4 ng/mg, P<0.001). The area under the receiver operating
      characteristic curve (AUC) indicated a sensitivity of 79.0%, specificity of 64.7%
      and a positive predictive value of 68.7%, with an AUC of 0.76 for increased alpha
      syn oligomer/total RBC protein ratio. However, there was no correlation between
      RBC alpha-syn oligomer levels and age at onset, disease duration, age, UPDRS
      motor scale score or progression of motor degeneration in PD patients. The ratio
      of RBC alpha-syn oligomer/total protein was also higher in MSA patients than in
      controls (22.9+/-13.9 ng/mg vs. 15.4+/-7.4 ng/mg, P<0.001). However, no
      significant difference was found for alpha-syn oligomer/total protein ratio
      between PD and MSA (29.0+/-19.8 ng/mg vs. 22.9+/-13.9 ng/mg, P>0.05). The present
      results suggest that the RBC alpha-syn oligomer/total protein ratio can be a
      potential diagnostic biomarker for PD.

PMID- 25998656
TI  - Community shifts in a well-operating agricultural biogas plant: how process
      variations are handled by the microbiome.
AB  - This study provides a comprehensive, long-term microbiological study of a
      continuously operated, mesophilic, agricultural biogas plant fed with whole-crop
      silages of maize and rye, cattle manure and cattle slurry. The microbial
      community structure was accessed by high-throughput 16S rRNA gene amplicon
      sequencing. For the characterisation of the microbial dynamics, the community
      profiling method terminal restriction fragment length polymorphism (TRFLP) in
      combination with a cloning-sequencing approach as well as a LC-MS/MS approach for
      protein identification were applied. Our results revealed that the anaerobic
      digestion is a highly sensitive process: small variations in the process
      performance induce fluctuations in the microbial community composition and
      activity. In this context, it could be proven that certain microbial species were
      better adapted to changing process condition such as temperature (interspecies
      competition) and that there is a physiological compensation between different
      microorganisms so that the reactor efficiency was not adversely affected despite
      of structural and functional changes within the microbial community. 

PMID- 25998657
TI  - Endogenic oxidative stress response contributes to glutathione over-accumulation
      in mutant Saccharomyces cerevisiae Y518.
AB  - Mechanisms of glutathione (GSH) over-accumulation in mutant Saccharomyces
      cerevisiae Y518 screened by ultraviolet and nitrosoguanidine-induced random
      mutagenesis were studied. Y518 accumulated higher levels of GSH and L-cysteine
      than its wild-type strain. RNA-Seq and pathway enrichment analysis indicated a
      difference in the expression of key genes involved in cysteine production, the
      GSH biosynthesis pathway, and antioxidation processes. GSH1, MET17, CYS4, GPX2,
      CTT1, TRX2, and SOD1 and the transcriptional activators SKN7 and YAP1 were up
      regulated in the mutant. Moreover, Y518 showed a dysfunctional respiratory chain
      resulting from dramatically weakened activity of complex III and significant
      elevation of intracellular reactive oxygen species (ROS) levels. The
      supplementation of antimycin A in the culture of the parent strain showed
      equivalent changes of ROS and GSH level. This study indicates that defective
      complex III prompts abundant endogenic ROS generation, which triggers an
      oxidative stress response and upregulation of gene expression associated with GSH
      biosynthesis. This finding may be helpful for developing new strategies for GSH
      fermentation process optimization or metabolic engineering.

PMID- 25998658
TI  - The direct anti-MRSA effect of emodin via damaging cell membrane.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become an important
      bacterium for nosocomial infection. Only a few antibiotics can be effective
      against MRSA. Therefore, searching for new drugs against MRSA is important.
      Herein, anti-MRSA activities of emodin and its mechanisms were investigated.
      Firstly, in vitro antimicrobial activity was investigated by minimum inhibitory
      concentration (MIC), minimum bactericidal concentration (MBC), and time-growth
      curve, and multipassage resistance testing was performed. Secondly, protection of
      emodin on mice survival and blood bacterial load in mice challenged with lethal
      or sublethal dose of MRSA were investigated. Subsequently, the influences of
      emodin on the bacterial morphology, messenger RNA (mRNA) expressions related to
      cell wall synthesis and lysis, beta-lactamase activity, drug accumulation,
      membrane fluidity, and integrity were performed to investigate its mechanisms.
      Lastly, in vitro cytotoxicity assay were performed using the 3-(4,5-dimethyl-2
      thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) method. The results showed
      MICs and MBCs of emodin against MRSA252 and 36 clinical MRSA strains were among 2
      8 and 4-32 MUg/mL, respectively. There was no MIC increase for emodin during 20
      passages. In vivo, emodin dose-dependently protected mice challenged with lethal
      dose of MRSA and decreased bacterial load in mice challenged with sublethal dose
      of MRSA. Morphology observation showed emodin might disrupt cell wall and
      membrane of MRSA. Although emodin had no influence on genes related to cell wall
      synthesis and lysis as well as beta-lactamase activity and drug accumulation,
      emodin reduced membrane fluidity and disrupted membrane integrity. Based on the
      fact that emodin had no significant cytotoxicity against mammalian cells, it
      could be further investigated as a membrane-damage bactericide against MRSA in
      the future. 

PMID- 25998659
TI  - A natural short pathway synthesizes roquefortine C but not meleagrin in three
      different Penicillium roqueforti strains.
AB  - The production of mycotoxins and other secondary metabolites in Penicillium
      roqueforti is of great interest because of its long history of use in blue-veined
      cheese manufacture. In this article, we report the cloning and characterization
      of the roquefortine gene cluster in three different P. roqueforti strains
      isolated from blue cheese in the USA (the type strain), France, and the UK
      (Cheshire cheese). All three strains showed an identical roquefortine gene
      cluster organization and almost identical (98-99%) gene nucleotide sequences in
      the entire 16.6-kb cluster region. When compared with the Penicillium chrysogenum
      roquefortine/meleagrin seven-gene cluster, the P. roqueforti roquefortine cluster
      contains only four genes (rds, rdh, rpt, and gmt) encoding the roquefortine
      dipeptide synthetase, roquefortine D dehydrogenase, roquefortine
      prenyltransferase, and a methyltransferase, respectively. Silencing of the rds or
      rpt genes by the RNAi strategy reduced roquefortine C production by 50%
      confirming the involvement of these two key genes in roquefortine biosynthesis.
      An additional putative gene, orthologous of the MFS transporter roqT, is
      rearranged in all three strains as a pseudogene. The same four genes and a
      complete (not rearranged) roqT, encoding a MFS transporter containing 12 TMS
      domains, occur in the seven-gene cluster in P. chrysogenum although organized
      differently. Interestingly, the two "late" genes of the P. chrysogenum
      roquefortine/meleagrin gene cluster that convert roquefortine C to glandicoline B
      and meleagrin are absent in the P. roqueforti four-gene cluster. No meleagrin
      production was detected in P. roqueforti cultures grown in YES medium, while P.
      chrysogenum produces meleagrin in these conditions. No orthologous genes of the
      two missing meleagrin synthesizing genes were found elsewhere in the recently
      released P. roqueforti genome. Our data suggest that during evolution, the seven
      gene cluster present in P. chrysogenum, and probably also in other
      glandicoline/meleagrin producing fungi, has been trimmed down to a short cluster
      in P. roqueforti leading to the synthesis of roquefortine C rather than meleagrin
      as a final product.

PMID- 25998660
TI  - A selection assay for haloalkane dehalogenase activity based on toxic substrates.
AB  - Based on natural selection and the survival of the fittest by evolutionary
      adaption, a smart high-throughput system was developed to select active
      haloalkane dehalogenase variants from a large mutant library. Only active enzyme
      variants can hydrolyse toxic halogenated alkanes to promote growth, whereas
      inactive mutants starve or die due to the toxic compound. With this powerful
      tool, huge enzyme mutant libraries can be screened within a few days. The
      selection is done without any artificial substrates that are hard to synthesize
      and they also resemble typical ones for haloalkane dehalogenases. Three
      saturation libraries, with a size of more than 10(6) cells, based on inactive
      variants of the haloalkane dehalogenases DhaA or DhlA were successfully screened
      to retrieve active enzymes. The enrichment of the active wild-type enzyme in
      contrast to the inactive variants was about 340-fold. In addition, this selection
      approach can be applied for continuous directed evolution experiments for the
      enrichment of cells expressing adapted haloalkane dehalogenases.

PMID- 25998662
TI  - NMR study of localization and mobility of 1-phenylethanol enantiomers in
      homochiral metal-organic sorbent Zn2(bdc)(S-lac)(dmf).
AB  - Structural features of localization of chiral isomers of 1-phenylethanol (R
      PhEtOH and S-PhEtOH) and their mobility activation in homochiral metal-organic
      [Zn2 (bdc)(S-lac)(dmf)] sorbent were studied with (1)H and (13)C NMR methods.
      (13)C NMR chemical shifts do not show obvious advantage of selective interaction
      of molecule guests. But activation molecular mobility of S-PhEtOH and R-PhEtOH
      clearly indicates that stabilization of [Zn2(bdc)(S-lac)(dmf)].S-PhEtOH structure
      is more preferable than stabilization of [Zn2 (bdc)(S-lac)(dmf)].R-PhEtOH
      structure.

PMID- 25998661
TI  - An observational study of the temporal and spatial patterns of Marek's-disease
      associated leukosis condemnation of young chickens in the United States of
      America.
AB  - Marek's disease, a disease primarily affecting immature chickens, is a worldwide
      problem that has on at least three occasions threatened the poultry industry in
      the United States. A rich dataset to study the epidemiology of this disease is
      available because the United States Department of Agriculture has required
      mandatory inspections of all commercially sold poultry of significant scale since
      the mid-20th century with over 99% of all chickens inspected. This dataset
      includes monthly totals aggregated by state since 1961 of the number of "young
      chickens" inspected and the number with "leukosis", a condemnation category that
      is almost always associated with Marek's disease in this category of birds. The
      objective of this study was to analyze temporal and spatial patterns in this
      condemnation data to gain insight into the ecology and epidemiology of the
      causative virus. We extracted visual patterns in the data using seasonal trend
      decomposition, and we tested for statistical significance using extended linear
      modeling techniques. The analysis confirmed previous findings that there are
      differences in leukosis condemnation rates between states, across years, and
      within years. The analysis also revealed several patterns not previously
      highlighted, including spatial and temporal autocorrelations in leukosis
      condemnation, changes to the amplitude of seasonality over time, and increasing
      within-year variation in condemnation rate over time. These patterns suggest that
      locally shared farm practices, virus transmission between farms, or viral
      persistence may be important to understanding the dynamics of the disease. We
      also discuss the plausibility of other potential explanations for these patterns.

PMID- 25998663
TI  - Treatment of atrial fibrillation: a weighty problem.

PMID- 25998664
TI  - Expanding the Transcatheter Aortic Valve Replacement Field Under Continued
      Surveillance: The GARY Registry.

PMID- 25998665
TI  - Well-Intended NOTION, Ahead of Practice.

PMID- 25998666
TI  - Left main revascularization: surgical and interventional perspectives.

PMID- 25998667
TI  - Double antiplatelet therapy duration: standardize or personalize?

PMID- 25998668
TI  - Bleeding avoidance strategies during percutaneous coronary interventions.
AB  - Bleeding avoidance strategies for percutaneous coronary interventions continue to
      evolve with the availability of newer antiplatelet and anticoagulation therapies.
      Advances in interventional practices have altered the balance between ischemic
      and bleeding complications. With the availability of rapidly-acting platelet
      adenosine diphosphate-receptor antagonists, the need for routine glycoprotein
      IIb/IIIa inhibitors has diminished. Recent meta-analyses and trials have advanced
      our knowledge of vascular access and different anticoagulation regimens. Vascular
      closure devices have long been used for early ambulation; however, more recent
      results demonstrating lower bleeding complications from observational registries
      are encouraging. This review synthesizes this information, taking into account
      changes in the landscape of interventional practice with respect to current
      bleeding avoidance strategies.

PMID- 25998670
TI  - The Capacity of Evidence to Inform Practice: The Rapid Registry Response (RRR)
      Initiative.

PMID- 25998669
TI  - Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism:
      mechanistic links and clinical inferences.
AB  - The association of atrial fibrillation (AF) with ischemic stroke has long been
      recognized; yet, the pathogenic mechanisms underlying this relationship are
      incompletely understood. Clinical schemas, such as the CHA2DS2-VASc (congestive
      heart failure, hypertension, age >= 75 years, diabetes mellitus, stroke/transient
      ischemic attack, vascular disease, age 65 to 74 years, sex category) score,
      incompletely account for thromboembolic risk, and emerging evidence suggests that
      stroke can occur in patients with AF even after sinus rhythm is restored. Atrial
      fibrosis correlates with both the persistence and burden of AF, and gadolinium
      enhanced magnetic resonance imaging is gaining utility for detection and
      quantification of the fibrotic substrate, but methodological challenges limit its
      use. Factors related to evolution of the thrombogenic fibrotic atrial
      cardiomyopathy support the view that AF is a marker of stroke risk regardless of
      whether or not the arrhythmia is sustained. Antithrombotic therapy should be
      guided by a comprehensive assessment of intrinsic risk rather than the presence
      or absence of AF at a given time.

PMID- 25998671
TI  - Training in adult congenital heart disease.

PMID- 25998672
TI  - Effect of patent foramen ovale closure on obstructive sleep apnea.

PMID- 25998673
TI  - Emergency department management of atrial fibrillation in the United States
      versus Ontario, Canada.

PMID- 25998674
TI  - Structural heart disease: tetralogy, transposition, and truncus, too?

PMID- 25998675
TI  - Reply: Structural heart disease: tetralogy, transposition, and truncus, too?

PMID- 25998676
TI  - Aortic Stiffening and Dilation: Influence on Coronary Supply-Demand Balance.

PMID- 25998677
TI  - Reply: Aortic stiffening and dilation: influence on coronary supply-demand
      balance.

PMID- 25998678
TI  - Food and the consumer: could labelling be the answer?
AB  - Extensive research into the impact of nutrition labelling across Europe has shown
      that many consumers can effectively use a nutrition label to rank a food for
      healthiness. The present paper considers observational and laboratory evidence
      which has examined the impact of nutrition labelling (on food packaging and at
      point of purchase) on dietary behaviour. In addition, the potential
      counterproductive effects of foods bearing 'healthy' nutrition labels are
      examined. The observational evidence provides a useful insight into the key
      characteristics of nutrition label use. Those most likely to engage with
      nutrition labels are more likely to have a diet related disease and/or be on a
      weight loss diet and have a good overall diet quality. Experimental evidence,
      while limited, suggests that serving size information may be overlooked by
      consumers. In fact, there may be a tendency among consumers to overeat foods that
      are perceived to be healthier. The findings from the present paper suggest that
      if nutrition labelling is to be considered a strategy to facilitate consumers in
      managing their energy intake, it must coincide with salient, consistent and
      simple serving size information on the front of food packages and at the point of
      purchase. There is a clear need for more experimental research using robust
      methodologies, to examine the impact of nutrition information on dietary intake.
      In the meantime, there should be greater attention given to portion size within
      national dietary guidance. 

PMID- 25998679
TI  - Designing interventions to change eating behaviours.
AB  - Understanding and changing eating behaviours are central to the work of Nutrition
      Society members working in both research and applied settings. The present paper
      describes a recently published resource to guide the design of interventions to
      change behaviour, The Behaviour Change Wheel: A Guide to Designing Interventions
      (BCW Guide). This is a practical guide to intervention design that brings
      together recently-developed theory-based tools in behavioural science into a
      coherent step-by-step design process. It is based on the BCW, a synthesis of
      nineteen frameworks of behaviour change found in the research literature. The BCW
      has at its core a model of behaviour known as 'capability', 'opportunity',
      'motivation' and 'behaviour'. The model recognises that behaviour is part of an
      interacting system involving all these components. The BCW identifies different
      intervention options that can be applied to changing each of the components and
      policies that can be adopted to deliver those intervention options. The book
      shows how the BCW links to theory-based frameworks to understand behaviour such
      as the Theoretical Domains Framework and the recently developed Behaviour Change
      Technique Taxonomy v1 for specifying intervention content. In essence, it shows
      how to link what is understood about a given behaviour to types of intervention
      likely to be effective and then translate this into a locally relevant
      intervention. In addition, the present paper sets out some principles of
      intervention design. 

PMID- 25998680
TI  - Imaging methodologies and applications for nutrition research: what can
      functional MRI offer? - ERRATUM.

PMID- 25998682
TI  - Structural organization of an intact phycobilisome and its association with
      photosystem II.
AB  - Phycobilisomes (PBSs) are light-harvesting antennae that transfer energy to
      photosynthetic reaction centers in cyanobacteria and red algae. PBSs are
      supermolecular complexes composed of phycobiliproteins (PBPs) that bear
      chromophores for energy absorption and linker proteins. Although the structures
      of some individual components have been determined using crystallography, the
      three-dimensional structure of an entire PBS complex, which is critical for
      understanding the energy transfer mechanism, remains unknown. Here, we report the
      structures of an intact PBS and a PBS in complex with photosystem II (PSII) from
      Anabaena sp. strain PCC 7120 using single-particle electron microscopy in
      combination with biochemical and molecular analyses. In the PBS structure, all
      PBP trimers and the conserved linker protein domains were unambiguously located,
      and the global distribution of all chromophores was determined. We provide
      evidence that ApcE and ApcF are critical for the formation of a protrusion at the
      bottom of PBS, which plays an important role in mediating PBS interaction with
      PSII. Our results provide insights into the molecular architecture of an intact
      PBS at different assembly levels and provide the basis for understanding how the
      light energy absorbed by PBS is transferred to PSII. 

PMID- 25998681
TI  - P2RX7 sensitizes Mac-1/ICAM-1-dependent leukocyte-endothelial adhesion and
      promotes neurovascular injury during septic encephalopathy.
AB  - Septic encephalopathy (SE) is a critical factor determining sepsis mortality.
      Vascular inflammation is known to be involved in SE, but the molecular events
      that lead to the development of encephalopathy remain unclear. Using time-lapse
      in vivo two-photon laser scanning microscopy, we provide the first direct
      evidence that cecal ligation and puncture in septic mice induces microglial
      trafficking to sites adjacent to leukocyte adhesion on inflamed cerebral
      microvessels. Our data further demonstrate that septic injury increased the
      chemokine CXCL1 level in brain endothelial cells by activating endothelial P2RX7
      and eventually enhanced the binding of Mac-1 (CD11b/CD18)-expressing leukocytes
      to endothelial ICAM-1. In turn, leukocyte adhesion upregulated endothelial
      CX3CL1, thereby triggering microglia trafficking to the injured site. The sepsis
      induced increase in endothelial CX3CL1 was abolished in CD18 hypomorphic mutant
      mice. Inhibition of the P2RX7 pathway not only decreased endothelial ICAM-1
      expression and leukocyte adhesion but also prevented microglia overactivation,
      reduced brain injury, and consequently doubled the early survival of septic mice.
      These results demonstrate the role of the P2RX7 pathway in linking neurovascular
      inflammation to brain damage in vivo and provide a rationale for targeting
      endothelial P2RX7 for neurovascular protection during SE. 

PMID- 25998683
TI  - Internalization of the TGF-beta type I receptor into caveolin-1 and EEA1 double
      positive early endosomes.
AB  - Endocytosis and intracellular sorting of transforming growth factor-beta (TGF
      beta) receptors play an important regulatory role in TGF-beta signaling. Two
      major endocytic pathways, clathrin- and caveolae-mediated endocytosis, have been
      reported to independently mediate the internalization of TGF-beta receptors. In
      this study, we demonstrate that the clathrin- and caveolae-mediated endocytic
      pathways can converge during TGF-beta receptor endocytic trafficking. By tracking
      the intracellular dynamics of fluorescently-labeled TGF-beta type I receptor
      (TbetaRI), we found that after mediating TbetaRI internalization, certain
      clathrin-coated vesicles and caveolar vesicles are fused underneath the plasma
      membrane, forming a novel type of caveolin-1 and clathrin double-positive
      vesicles. Under the regulation of Rab5, the fused vesicles are targeted to early
      endosomes and thus deliver the internalized TbetaRI to the caveolin-1 and EEA1
      double-positive early endosomes (caveolin-1-positive early endosomes). We further
      showed that the caveolin-1-positive early endosomes are positive for Smad3/SARA,
      Rab11 and Smad7/Smurf2, and may act as a multifunctional device for TGF-beta
      signaling and TGF-beta receptor recycling and degradation. Therefore, these
      findings uncover a novel scenario of endocytosis, the direct fusion of clathrin
      coated and caveolae vesicles during TGF-beta receptor endocytic trafficking,
      which leads to the formation of the multifunctional sorting device, caveolin-1
      positive early endosomes, for TGF-beta receptors. 

PMID- 25998684
TI  - Accuracy of PaO2 /FiO2 calculated from SpO2 for severity assessment in ED
      patients with pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Assessment of oxygenation in patients with community
      acquired pneumonia is critical for treatment. The accuracy of percutaneous oxygen
      saturation (SpO2 ) determined by pulse oximetry is uncertain, and it has limited
      value in patients receiving supplemental oxygen. We hypothesized that calculation
      of partial arterial oxygen concentration/inspired oxygen faction (PaO2 /FiO2 )
      from SpO2 by the Ellis or Rice equations might adequately correlate with PaO2
      /FiO2 measured by arterial blood gases. METHODS: We studied 1004 patients with
      pneumonia in the emergency department with simultaneous measurement of SpO2 and
      PaO2 from two cohorts from Valencia, Spain and Utah, USA. We compared SpO2 with
      measured SaO2 , compared the equations' accuracy in calculating PaO2 /FiO2 and
      determined how often patients would be misclassified at clinically important
      thresholds. We compared estimated PaO2 /FiO2 to measured PaO2 /FiO2 using the
      Spearman correlation. RESULTS: Pairwise correlation of SpO2 with SaO2 was
      moderate (rho = 0.66; P < 0.01). Both equations performed similarly among
      patients with lower PaO2 /FiO2 ratios. The Ellis equation estimated PaO2 /FiO2
      from SpO2 more accurately than the Rice equation in patients with PaO2 /FiO2
      >=200. Simple agreement between calculated and measured P/F was 91% and 92%,
      respectively. CONCLUSIONS: The Ellis equation was more accurate than the Rice
      equation for estimating PaO2 /FiO2 , especially at higher levels of P/F ratio.
      Estimation of PaO2 /FiO2 from SpO2 is accurate enough for initial oxygenation
      assessment. Ellis and Rice equations could misclassify 20% and 30% of patients,
      respectively, at higher levels of PaO2 /FiO2 . For patients with abnormal
      oxygenation falling near thresholds for clinical decision making, arterial blood
      gas measurement preferably on room air is more accurate.

PMID- 25998685
TI  - Effect of Osteotomy Position and Tibial Plateau Rotation on the Tensile Force
      Required for Failure of the Canine Quadriceps Mechanism.
AB  - OBJECTIVE: To measure the tensile force required for failure of the quadriceps
      mechanism with different tibial tuberosity widths and different degrees of
      rotation of the tibial plateau after radial osteotomy of the proximal tibia.
      STUDY DESIGN: Ex vivo study, randomized unblocked design ANIMALS: Thirty-five
      hind limbs from 18 adult Greyhound cadavers. METHODS: Part 1 (15 limbs)--The
      center of rotation of the proximal tibial radial osteotomy was advanced
      craniodistally, progressively reducing absolute tibial tuberosity width (ATTW)
      for 5 different widths. Part 2 (21 limbs)-Tibial plateau rotation was performed
      at a set ATTW. Rotation was varied as a function of tibial tuberosity position
      with rotation proximal, level with, or distal to the tuberosity. All 35 limbs
      were tested with force applied via the quadriceps mechanism until construct
      failure occurred. RESULTS: All but 2 limbs failed by fracture of the tibial
      tuberosity. The tensile force required for failure of the quadriceps mechanism
      increased linearly with increasing ATTW. Significantly less force (P = .016) was
      required for failure of the quadriceps mechanism when the rotation of the tibial
      plateau was distal to the level of the patella tendon (mean 1,877 N) compared to
      when it was above the level of the patella tendon (mean 2,533 N). Rotation of the
      tibial plateau distal to the level of the patella tendon insertion point resulted
      in fracture at the base of the tibial tuberosity, level with the tibial plateau
      buttress. CONCLUSION: The overwhelming mode of failure of the quadriceps
      mechanism was by tibial tuberosity fracture, thus this was the weakest part of
      the construct. Reducing the tibial tuberosity width and rotation of the tibial
      plateau segment below the patella tendon insertion decreased the force required
      for tibial tuberosity fracture. These results support the idea of a safe point
      with the tibial plateau segment providing buttress to the tibial tuberosity.

PMID- 25998686
TI  - The interaction of Eu(III) with organoborates - a further approach to understand
      the complexation in the An/Ln(III)-borate system.
AB  - The formation equilibria of salicylatoborate, lactatoborate and 3
      hydroxybutyratoborate were studied by means of (11)B NMR spectroscopy. The
      smaller the pKa of the respective organic acid, the higher is the formation
      constant of the organoborate. The complexation of Eu(III) with salicylatoborate
      and lactatoborate was investigated by means of TRLFS (time-resolved laser-induced
      fluorescence spectroscopy) and (11)B NMR spectroscopy, yielding complexation
      constants lg beta110 = 2.6-3.2. A Eu(III)-3-hydroxybutyrate complex was
      characterized by TRLFS and (1)H NMR spectroscopy (lg beta110 = 2.89). DFT
      calculations of the investigated Eu(III)-organoborates and inorganic Eu(III)
      (poly)borates provided information about the Eu(III) coordination (most likely
      chelate). They support the hypothesis that the complexation of Eu(III) with
      organic as well as inorganic borate structures containing the binding site
      "B(OR)4(-)" (R = H, threefold coordinated boron center(s), organic moiety) is
      comparable.

PMID- 25998687
TI  - Vascular and inflammatory actions of P2X receptors in renal injury.
AB  - P2 purinergic receptors are activated by extracellular ATP and subserve a
      plethora of roles in the body, including metabolism, inflammation and neuronal
      signalling. This review focuses on renal purinergic receptors and how different
      roles that they play may contribute to renal dysfunction and the progression of
      chronic kidney disease. Numerous studies have linked P2 receptors, particularly
      the P2X4R and P2X7R subtypes, to kidney injury and damage. However, the
      mechanisms underlying this association are not fully defined. Several studies
      show that activation of P2X4R and particularly P2X7R can have a pro-inflammatory
      effect, causing or exacerbating damage to renal tissue. However, clinical trials
      aiming to utilise P2X7R antagonists to treat inflammatory disease have been
      unsuccessful, and it is possible that other mechanisms besides inflammation tie
      P2X7R activation to disease progression. In this context, purinergic signalling
      is also involved in the control of vascular tone and our recent studies suggest
      that activation of P2X4R/P2X7R causes renal vascular dysfunction and contributes
      to chronic kidney disease. This brief review aims to summarise the complementary
      inflammatory and vascular roles of P2X receptors in the kidney, with emphasis on
      the subtypes P2X4R and P27XR, and how each contributes to and presents
      therapeutic targets in the progression of chronic kidney disease. 

PMID- 25998688
TI  - Establishment and characterization of gemcitabine-resistant human
      cholangiocarcinoma cell lines with multidrug resistance and enhanced
      invasiveness.
AB  - To establish and characterize the gemcitabine-resistant cholangiocarcinoma (CCA)
      cell lines, CCA KKU-M139 and KKU-M214 cell lines were exposed stepwisely to
      increasing gemcitabine (GEM). The resultant drug-resistant cell lines, KKU
      M139/GEM and KKU-M214/GEM, retained the resistant phenotype in drug-free medium
      at least for 2 months. Sulforhodamine B assay demonstrated that KKU-M139/GEM and
      KKU-M214/GEM were 25.88- and 62.31-fold more resistant to gemcitabine than their
      parental cells. Both gemcitabine-resistant cell lines were cross-resistant to 5
      fluorouracil (5-FU), doxorubicin and paclitaxel indicating their multidrug
      resistant nature. Using reverse transcriptase-polymerase chain reaction (RT-PCR),
      real-time PCR and western blot analyses, gemcitabine-resistant cells showed
      upregulation of RRM1 and downregulation of hENT1 and dCK. In relation to
      multidrug resistance, these cell lines showed upregulation of multidrug
      resistance protein 1 (MRP1) leading to an increase of drug efflux. Using cell
      adhesion and Boyden chamber transwell assays, these cell lines also showed higher
      cell adhesion, migration and invasion capabilities via the activations of protein
      kinase C (PKC), focal adhesion kinase (FAK), extracellular signal-regulated
      kinase-1/2 (ERK1/2) and nuclear factor-kappaB (NF-kappaB). Higher activity of
      matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) was
      also observed by a gelatin zymography assay and a casein-plasminogen zymography
      assay. Flow cytometry analysis indicated the G2/M arrest regulated by
      downregulation of cyclin B1 and cyclin-dependent kinase 1 (Cdk1) resulted in an
      extended population doubling time. Using Annexin V/propidium iodide staining,
      evasion of apoptosis via an intrinsic pathway was observed in both cell lines in
      association with upregulation of Bcl-2 and downregulation of Bax. Interestingly,
      Fas was additionally downregulated in KKU-M214/GEM supporting the view of its
      higher GEM resistant characteristics. These findings indicate that long-term
      exposure of CCA cell lines to gemcitabine induce not only multidrug resistance
      but also enhance their invasiveness.

PMID- 25998689
TI  - Dual function of CALCOCO2/NDP52 during xenophagy.
AB  - During xenophagy, pathogens are selectively targeted by autophagy receptors to
      the autophagy machinery for their subsequent degradation. In infected cells, the
      autophagy receptor CALCOCO2/NDP52 targets Salmonella Typhimurium to the
      phagophore membrane by concomitantly interacting with LC3C and binding to
      ubiquitinated cytosolic bacteria or to LGALS8/GALECTIN 8 adsorbed on damaged
      vacuoles that contain bacteria. We recently reported that in addition, CALCOCO2
      is also necessary for the maturation step of Salmonella Typhimurium-containing
      autophagosomes. Interestingly, the role of CALCOCO2 in maturation is independent
      of its role in targeting, as these functions rely on distinct binding domains and
      protein partners. Indeed, to mediate autophagosome maturation CALCOCO2 binds on
      the one hand to LC3A, LC3B, or GABARAPL2, and on the other hand to MYO6/MYOSIN
      VI, whereas the interaction with LC3C is dispensable. Therefore, the autophagy
      receptor CALCOCO2 plays a dual function during xenophagy first by targeting
      bacteria to nascent autophagosomes and then by promoting autophagosome maturation
      in order to destroy bacteria. 

PMID- 25998690
TI  - Expression of miRNAs in Bull Spermatozoa Correlates with Fertility Rates.
AB  - Bull spermatozoa are rich in active miRNAs, and it has been shown that specific
      spermborne miRNAs can be linked to fertility. Thus, expression profiling of
      spermatozoa could be helpful for understanding male fertility and the ability of
      spermatozoa to initiate and sustain zygotic, embryonic and foetal development.
      Herein we hypothesized that bulls with moderate to high fertility can be
      identified by differences in amounts of certain miRNAs between their ejaculates.
      RNA samples from spermatozoa of eight brother pairs (one bull with high and one
      with moderate NRR in each pair) of the Holstein breed were prepared. miRNA was
      isolated, and the expression of 178 miRNAs was determined by RT-qPCR. Important
      findings were that highly expressed miRNAs, not linked to NRR status, were
      identified in the bull sperm samples, which indicate that these miRNAs have an
      important role in early embryogenesis. A large fraction of the targets genes were
      phosphoproteins and genes involved in the regulation of transcription. Seven
      miRNAs (mir-502-5p, mir-1249, mir-320a, mir-34c-3p, mir-19b-3p, mir-27a-5p and
      mir-148b-3p) were differentially expressed between bulls with moderate and high
      NRR with a strong tendency towards a higher expression of miRNAs in bulls with
      moderate fertility. Thus, bulls with a moderate NRR negatively regulate the
      expression of protein-coding genes, which leads to problems during the pregnancy.

PMID- 25998691
TI  - Historical Aspects of Lithopaidion: Handle with Care.

PMID- 25998692
TI  - Bubbles in Ballooning: Safety and Utility.

PMID- 25998693
TI  - Detection of thyroglobulin in antithyroglobulin antibody-positive sera by
      isoelectric focusing.
AB  - Circulating antibodies have the potential to interfere with the measurement of
      thyroglobulin (Tg) in sera of patients. Here, we determined Tg concentration by
      isoelectric focusing (IEF) on agarose gel using for detection a rabbit antiserum
      to human Tg termed FLX. Tg was determined in sera of thyroid patients and HIV
      infected patients under antiviral therapy. We showed that Tg IEF was not affected
      by the presence of anti-Tg antibodies (TgAb). Tg concentrations measured by IEF
      in TgAb-negative sera were in most of the cases, similar to those obtained by
      IRMA (immunoradiometric assay). However, in 5 of the 96 thyroid patients, and
      none of the 46 healthy subjects, Tg was undetectable by antiserum FLX and
      measurable by IRMA. In HIV-infected patients (64 men and 60 women), Tg was not
      recognized by FLX in 23 men and 9 women and this was related to abnormal CD4. We
      hypothesize that the decreased binding of FLX to Tg may be the result of
      conformational change on the Tg molecule, a phenomenon apparently related to
      immunodeficiency in HIV-infected patients. For thyroid patients, Tg IEF may be
      very useful for the interpretation of results when Tg measurements by IRMA and
      automated immunoassays are affected by interferences. 

PMID- 25998694
TI  - MicroRNA-204 inhibits proliferation, migration, invasion and epithelial
      mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1.
AB  - MicroRNAs (miRs) play crucial roles in tumorigenesis by directly suppressing the
      protein expression levels of their target genes. miR-204 has been suggested to
      act as a tumor suppressor in several types of human cancer. However, the exact
      role of miR-204 in osteosarcoma (OS) remains undetermined. In the present study,
      we aimed to investigate the effects of miR-204 on OS cell proliferation,
      migration and invasion, as well as the underlying molecular mechanisms. We found
      that the expression of miR-204 was frequently downregulated in four OS cell lines
      compared to the level in normal human osteoblast cells. Moreover, overexpression
      of miR-204 significantly inhibited the proliferation, migration and invasion of
      OS cells. Based on bioinformatics prediction and a luciferase reporter assay, we
      identified Sirtuin 1 (Sirt1) as a direct target gene of miR-204 in OS Saso-2
      cells. Moreover, the protein expression of Sirt1 was negatively mediated by miR
      204 in the OS cells. siRNA-mediated knockdown of Sirt1 also inhibited the
      proliferation, migration and invasion of the OS cells. Moreover, overexpression
      of Sirt1 reversed the inhibitory effect of miR-204 overexpression on the
      proliferation, migration and invasion of the OS cells. In addition, after miR-204
      overexpression or Sirt1 knockdown in OS cells, the expression of E-cadherin was
      increased, while the N-cadherin protein level was reduced. Based on these
      findings, we suggest that miR-204 inhibits the proliferation, migration, invasion
      and epithelial-mesenchymal transition (EMT) of OS cells by directly targeting
      Sirt1.

PMID- 25998695
TI  - Intestinal farnesoid X receptor puts a fresh coat of wax on fatty liver.

PMID- 25998696
TI  - Partially Oxidized Sub-10 nm MnO Nanocrystals with High Activity for Water
      Oxidation Catalysis.
AB  - The oxygen evolution reaction (OER) is considered a major bottleneck in the
      overall water electrolysis process. In this work, highly active manganese oxide
      nano-catalysts were synthesized via hot injection. Facile surface treatment
      generated Mn(III) species on monodisperse 10 nm MnO nanocrystals (NCs). Size
      dependency of MnO NCs on OER activity was also investigated. Surprisingly, the
      partially oxidized MnO NCs only required 530 mV @ 5 mA cm(-2) under near neutral
      conditions.

PMID- 25998697
TI  - Ca2+ dysregulation in the endoplasmic reticulum related to Alzheimer's disease: A
      review on experimental progress and computational modeling.
AB  - Alzheimer's disease (AD) is a devastating, incurable neurodegenerative disease
      affecting millions of people worldwide. Dysregulation of intracellular Ca(2+)
      signaling has been observed as an early event prior to the presence of clinical
      symptoms of AD and is believed to be a crucial factor contributing to its
      pathogenesis. The progressive and sustaining increase in the resting level of
      cytosolic Ca(2+) will affect downstream activities and neural functions. This
      review focuses on the issues relating to the increasing Ca(2+) release from the
      endoplasmic reticulum (ER) observed in AD neurons. Numerous research papers have
      suggested that the dysregulation of ER Ca(2+) homeostasis is associated with
      mutations in the presenilin genes and amyloid-beta oligomers. These disturbances
      could happen at many different points in the signaling process, directly
      affecting ER Ca(2+) channels or interfering with related pathways, which makes it
      harder to reveal the underlying mechanisms. This review paper also shows that
      computational modeling is a powerful tool in Ca(2+) signaling studies and
      discusses the progress in modeling related to Ca(2+) dysregulation in AD
      research. 

PMID- 25998698
TI  - Importance of binaural hearing.
AB  - An essential task for the central auditory pathways is to parse the auditory
      messages sent by the two cochleae into auditory objects, the segregation and
      localisation of which constitute an important means of separating target signals
      from noise and competing sources. When hearing losses are too asymmetric, the
      patients face a situation in which the monaural exploitation of sound messages
      significantly lessens their performance compared to what it should be in a
      binaural situation. Rehabilitation procedures must aim at restoring as many
      binaural advantages as possible. These advantages encompass binaural redundancy,
      head shadow effect and binaural release from masking, the principles and
      requirements of which make up the topic of this short review. Notwithstanding the
      complete understanding of their neuronal mechanisms, empirical data show that
      binaural advantages can be restored even in situations in which faultless
      symmetry is inaccessible.

PMID- 25998699
TI  - Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and
      Frontotemporal Dementia.
AB  - As dementia is a fast-growing health care problem, it is becoming an increasingly
      urgent need to provide an early diagnosis in order to offer patients the best
      medical treatment and care. Validated biomarkers which reflect the pathology and
      disease progression are essential for diagnosis and are important when developing
      new therapies. Today, the core protein biomarkers amyloid-beta42, total tau and
      phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose
      Alzheimer's disease (AD), because these biomarkers have shown to reflect the
      underlying amyloid and tau pathology. However, the biomarkers have proved
      insufficient predictors of dementias with a different pathology, e.g.
      frontotemporal dementia (FTD); furthermore, the biomarkers are not useful for
      early AD diagnosis. Familial dementias with a known disease-causing mutation can
      be extremely valuable to study; yet the biomarker profiles in patients with
      familial dementias are not clear. This review summarizes CSF biomarker findings
      from studies on symptomatic and presymptomatic individuals carrying a mutation in
      one of the genes known to cause early-onset familial AD or FTD. In conclusion,
      the biomarker profile of inherited AD is quite similar between carriers of
      different mutations as well as similar to the profile found in sporadic AD,
      whereas familial FTD does not seem to have a clear biomarker profile. Hence, new
      biomarkers are needed for FTD.

PMID- 25998701
TI  - Physicochemical properties of tadalafil solid dispersions - Impact of polymer on
      the apparent solubility and dissolution rate of tadalafil.
AB  - To improve solubility of tadalafil (Td), a poorly soluble drug substance
      (3MUg/ml) belonging to the II class of the Biopharmaceutical Classification
      System, its six different solid dispersions (1:1, w/w) in the following polymers:
      HPMC, MC, PVP, PVP-VA, Kollicoat IR and Soluplus were successfully produced by
      freeze-drying. Scanning electron microscopy showed a morphological structure of
      solid dispersions typical of lyophilisates. Apparent solubility and intrinsic
      dissolution rate studies revealed the greatest, a 16-fold, increase in drug
      solubility (50MUg/ml) and a significant, 20-fold, dissolution rate enhancement
      for the Td/PVP-VA solid dispersion in comparison with crystalline Td. However,
      the longest duration of the supersaturation state in water (27MUg/ml) over 24h
      was observed for the Td solid dispersion in HPMC. The improved dissolution of Td
      from Td/PVP-VA was confirmed in the standard dissolution test of capsules filled
      with solid dispersions. Powder X-ray diffraction and thermal analysis showed the
      amorphous nature of these binary systems and indicated the existence of
      dispersion at the molecular level and its supersaturated character, respectively.
      Nevertheless, as evidenced by film casting, the greatest ability to dissolve Td
      in polymer was determined for PVP-VA. The crystallization tendency of Td
      dispersed in Kollicoat IR could be explained by the low Tg (113 degrees C) of the
      solid dispersion and the highest difference in Hansen solubility parameters
      (6.8MPa(0.5)) between Td and the polymer, although this relationship was not
      satisfied for the partially crystalline dispersion in PVP. Similarly, no
      correlation was found between the strength of hydrogen bonds investigated using
      infrared spectroscopy and the physical stability of solid dispersions or the
      level of supersaturation in aqueous solution. 

PMID- 25998703
TI  - Heparin inhibits lipopolysaccharide-induced inflammation via inducing caveolin-1
      and activating the p38/mitogen-activated protein kinase pathway in murine
      peritoneal macrophages.
AB  - Heparin is a soluble glycosaminoglycan largely used as an anti-coagulant drug and
      with well known anti-inflammatory effects. However, heparin is currently not used
      as an anti-inflammatory agent in the clinic due to a risk of bleeding as well as
      its complex mechanism of action. The underlying mechanism of the anti
      inflammatory action of heparin and its effector targets have remained to be fully
      elucidated. The present study confirmed the anti-inflammatory effects of heparin
      in lipopolysaccharide (LPS)-induced murine peritoneal macrophages through
      decreasing the levels of the inflammatory cytokines tumor necrosis factor alpha
      (TNF-alpha), interleukin 6 (IL-6), IL-8 and IL-1beta. Caveolin-1 participated in
      the anti-inflammatory process and it was able to be induced by heparin.
      Transfection of small interfering RNA of caveolin-1 into murine peritoneal
      macrophages attenuated the anti-inflammatory effects of heparin. Furthermore,
      following caveolin-1 silencing, the p38/mitogen-activated protein kinase (MAPK)
      pathway was still able to be activated by heparin, while the extracellular signal
      regulated kinase and c-Jun N-terminal kinase pathways were inhibited. In
      conclusion, these results suggested that heparin inhibits LPS-induced
      inflammation via inducing caveolin-1 and activating the p38/MAPK pathway in
      murine peritoneal macrophages. Revealing the anti-inflammatory mechanisms of
      heparin will aid in its development for clinical treatment in the future.

PMID- 25998700
TI  - Development of a highly thermostable, adjuvanted human papillomavirus vaccine.
AB  - A major impediment to economical, worldwide vaccine distribution is the
      requirement for a "cold chain" to preserve antigenicity. We addressed this
      problem using a model human papillomavirus (HPV) vaccine stabilized by
      immobilizing HPV16 L1 capsomeres, i.e., pentameric subunits of the virus capsid,
      within organic glasses formed by lyophilization. Lyophilized glass and liquid
      vaccine formulations were incubated at 50 degrees C for 12weeks, and then
      analyzed for retention of capsomere conformational integrity and the ability to
      elicit neutralizing antibody responses after immunization of BALB/c mice.
      Capsomeres in glassy-state vaccines retained tertiary and quaternary structure,
      and critical conformational epitopes. Moreover, glassy formulations adjuvanted
      with aluminum hydroxide or aluminum hydroxide and glycopyranoside lipid A were
      not only as immunogenic as the commercially available HPV vaccine Cervarix(r),
      but also retained complete neutralizing immunogenicity after high-temperature
      storage. The thermal stability of such adjuvanted vaccine powder preparations may
      thus eliminate the need for the cold chain. 

PMID- 25998702
TI  - Physical exercise counteracts genetic susceptibility to depression.
AB  - BACKGROUND/AIMS: Depression is a highly prevalent disorder in elderly
      individuals. A genetic variant (rs6265) of the brain-derived neurotrophic factor
      (BDNF) impacting on emotion processing is known to increase the risk for
      depression. We aim to investigate whether intensive endurance sports might
      attenuate this genetic susceptibility in a cohort of elderly marathon athletes.
      METHODS: Fifty-five athletes and 58 controls were included. rs6265 of the BDNF
      gene was genotyped by the TaqMan method. Depressive symptoms were assessed by
      standardized self-rating tests (BDI = Beck Depression Inventory, GDS = Geriatric
      Depression Scale). RESULTS: In multivariable analysis of BDI and GDS scores, the
      interaction between group (athletes vs. controls) and genotypes ([C];[C] vs.
      [C];[T] + [T];[T]) was found to be statistically significant (BDI: p = 0.027,
      GDS: p = 0.013). Among [C];[C] carriers, merely controls had an increased
      relative risk of 3.537 (95% CI = 1.276-9.802) of achieving a subclinical
      depression score >=10 on the BDI. There was no such effect in carriers of the [T]
      allele. In a multivariable binary logistic regression, genetic information, group
      (athletes/controls), but no information on rs6265 allele carrier status presented
      as a significant predictor of BDI scores >=10. CONCLUSION: Physical exercise
      positively affects BDNF effects on mood. Since 66Met BDNF secretion is impaired,
      this effect seems to be much stronger in [C];[C] homozygous individuals
      expressing the 66Val variant. This confirms that genetic susceptibility to
      depressive symptoms can indeed be influenced by endurance sports in elderly
      people.

PMID- 25998704
TI  - Prescription errors before and after introduction of electronic medication alert
      system in a pediatric emergency department.
AB  - OBJECTIVES: Prescription errors occur frequently in pediatric emergency
      departments (PEDs).The effect of computerized physician order entry (CPOE) with
      electronic medication alert system (EMAS) on these is unknown. The objective was
      to compare prescription errors rates before and after introduction of CPOE with
      EMAS in a PED. The hypothesis was that CPOE with EMAS would significantly reduce
      the rate and severity of prescription errors in the PED. METHODS: A prospective
      comparison of a sample of outpatient, medication prescriptions 5 months before
      and after CPOE with EMAS implementation (7,268 before and 7,292 after) was
      performed. Error types and rates, alert types and significance, and physician
      response were noted. Medication errors were deemed significant if there was a
      potential to cause life-threatening injury, failure of therapy, or an adverse
      drug effect. RESULTS: There was a significant reduction in the errors per 100
      prescriptions (10.4 before vs. 7.3 after; absolute risk reduction = 3.1, 95%
      confidence interval [CI] = 2.2 to 4.0). Drug dosing error rates decreased from 8
      to 5.4 per 100 (absolute risk reduction = 2.6, 95% CI = 1.8 to 3.4). Alerts were
      generated for 29.6% of prescriptions, with 45% involving drug dose range
      checking. The sensitivity of CPOE with EMAS in identifying errors in
      prescriptions was 45.1% (95% CI = 40.8% to 49.6%), and the specificity was 57%
      (95% CI = 55.6% to 58.5%). Prescribers modified 20% of the dosing alerts,
      resulting in the error not reaching the patient. Conversely, 11% of true dosing
      alerts for medication errors were overridden by the prescribers: 88 (11.3%)
      resulted in medication errors, and 684 (88.6%) were false-positive alerts.
      CONCLUSIONS: A CPOE with EMAS was associated with a decrease in overall
      prescription errors in our PED. Further system refinements are required to reduce
      the high false-positive alert rates.

PMID- 25998705
TI  - Drug delivery: Get in there!

PMID- 25998706
TI  - Therapeutic resistance: Fibroblasts restrain drug sensitivity.

PMID- 25998707
TI  - Immunotherapy: Put your coat on!

PMID- 25998710
TI  - Non-coding RNA: Stressed to bits.

PMID- 25998712
TI  - MicroRNA biogenesis pathways in cancer.
AB  - MicroRNAs (miRNAs) are critical regulators of gene expression. Amplification and
      overexpression of individual 'oncomiRs' or genetic loss of tumour suppressor
      miRNAs are associated with human cancer and are sufficient to drive tumorigenesis
      in mouse models. Furthermore, global miRNA depletion caused by genetic and
      epigenetic alterations in components of the miRNA biogenesis machinery is
      oncogenic. This, together with the recent identification of novel miRNA
      regulatory factors and pathways, highlights the importance of miRNA dysregulation
      in cancer. 

PMID- 25998713
TI  - Hijacked in cancer: the KMT2 (MLL) family of methyltransferases.
AB  - Histone-lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on
      the histone H3 tail at important regulatory regions in the genome and thereby
      impart crucial functions through modulating chromatin structures and DNA
      accessibility. Although the human KMT2 family was initially named the mixed
      lineage leukaemia (MLL) family, owing to the role of the first-found member KMT2A
      in this disease, recent exome-sequencing studies revealed KMT2 genes to be among
      the most frequently mutated genes in many types of human cancers. Efforts to
      integrate the molecular mechanisms of KMT2 with its roles in tumorigenesis have
      led to the development of first-generation inhibitors of KMT2 function, which
      could become novel cancer therapies. 

PMID- 25998714
TI  - Radioimmunotherapy of human tumours.
AB  - The eradication of cancer remains a vexing problem despite recent advances in our
      understanding of the molecular basis of neoplasia. One therapeutic approach that
      has demonstrated potential involves the selective targeting of radionuclides to
      cancer-associated cell surface antigens using monoclonal antibodies. Such
      radioimmunotherapy (RIT) permits the delivery of a high dose of therapeutic
      radiation to cancer cells, while minimizing the exposure of normal cells.
      Although this approach has been investigated for several decades, the cumulative
      advances in cancer biology, antibody engineering and radiochemistry in the past
      decade have markedly enhanced the ability of RIT to produce durable remissions of
      multiple cancer types. 

PMID- 25998717
TI  - Robot-Assisted Training Early After Cardiac Surgery.
AB  - BACKGROUND: To assess feasibility and safety of a robot-assisted gait therapy
      with the Lokomat(r) system in patients early after open heart surgery. METHODS:
      Within days after open heart surgery 10 patients were subjected to postoperative
      Lokomat(r) training (Intervention group, IG) whereas 20 patients served as
      controls undergoing standard postoperative physiotherapy (Control group, CG). All
      patients underwent six-minute walk test and evaluation of the muscular strength
      of the lower limbs by measuring quadriceps peak force. The primary safety end
      point was freedom from any device-related wound healing disturbance. Patients
      underwent clinical follow-up after one month. RESULTS: Both training methods
      resulted in an improvement of walking distance (IG [median, interquartile range,
      p-value]: +119 m, 70-201 m, p = 0.005; CG: 105 m, 57-152.5m, p < 0.001) and
      quadriceps peak force (IG left: +5 N, 3.8 7 N, p = 0.005; IG right: +3.5 N, 1.5
      8.8 N, p = 0.011; CG left: +5.5 N, 4-9 N, p < 0.001; CG right: +6 N, 4.3-9.8 N, p
      < 0.001) in all participants. Results with robot-assisted training were
      comparable to early postoperative standard in hospital training (median changes
      in walking distance in percent, p = 0.81; median changes in quadriceps peak force
      in percent, left: p = 0.97, right p = 0.61). No deep sternal wound infection or
      any adverse event occurred in the robot-assisted training group. CONCLUSIONS:
      Robot-assisted gait therapy with the Lokomat(r) system is feasible and safe in
      patients early after median sternotomy. Results with robot-assisted training were
      comparable to standard in hospital training. An adapted and combined aerobic and
      resistance training intervention with augmented feedback may result in benefits
      in walking distance and lower limb muscle strength (ClinicalTrials.gov number,
      NCT 02146196).

PMID- 25998715
TI  - Building better monoclonal antibody-based therapeutics.
AB  - For 20 years, monoclonal antibodies (mAbs) have been a standard component of
      cancer therapy, but there is still much room for improvement. Efforts continue to
      build better cancer therapeutics based on mAbs. Anticancer mAbs function through
      various mechanisms, including directly targeting the malignant cells, modifying
      the host response, delivering cytotoxic moieties and retargeting cellular
      immunity towards the malignant cells. Characteristics of mAbs that affect their
      efficacy include antigen specificity, overall structure, affinity for the target
      antigen and how a mAb component is incorporated into a construct that can trigger
      target cell death. This Review discusses the various approaches to using mAb
      based therapeutics to treat cancer and the strategies used to take advantage of
      the unique potential of each approach, and provides examples of current mAb-based
      treatments. 

PMID- 25998718
TI  - Effectiveness of 308-nm Excimer Laser Therapy in Treating Alopecia Areata,
      Determined by Examining the Treated Sides of Selected Alopecic Patches.
AB  - BACKGROUND: Some studies have reported the use of 308-nm excimer laser therapy
      for treating alopecia areata (AA); however, the effectiveness of this therapy on
      a theoretical basis has not yet been comparatively analyzed. OBJECTIVES: To
      determine the therapeutic effect of excimer laser therapy on AA. METHODS: One
      alopecic patch was divided into control and treated sides in 10 patients with AA.
      Then, 308-nm excimer laser therapy was administered twice a week for 12 weeks.
      Photograph and phototrichogram analyses were performed. RESULTS: Photographic
      assessments by both dermatologists and individuals of the general population
      showed objective improvements after excimer laser therapy. On the treated side,
      the hair count and hair diameter had statistically increased after treatment.
      However, only the hair diameter was found to be significantly high in the treated
      half when it was compared with the control side. CONCLUSION: The 308-nm excimer
      laser has a therapeutic effect on AA, which is proven by photograph and
      phototrichogram analysis by a side-by-side comparison.

PMID- 25998719
TI  - Soft tissue thickness values for black and coloured South African children aged 6
      13 years.
AB  - In children, craniofacial changes due to facial growth complicate facial
      approximations and require specific knowledge of soft tissue thicknesses (STT).
      The lack of South African juvenile STT standards of particular age groups, sex
      and ancestry is problematic. According to forensic artists in the South African
      Police Service the use of African-American values to reconstruct faces of Black
      South African children yields poor results. In order to perform a facial
      approximation that presents a true reflection of the child in question,
      information regarding differences in facial soft tissue at different ages, sexes
      and ancestry groups is needed. The aims of this study were to provide data on STT
      of South African Black and Coloured children and to assess differences in STT
      with respect to age, sex and ancestry. STT was measured using cephalograms of
      South African children (n=388), aged 6-13 years. After digitizing the images, STT
      measurements were taken at ten mid-facial landmarks from each image using the
      iTEM measuring program. STT comparisons between groups per age, sex and ancestry
      were statistically analyzed. The results showed that STT differences at lower
      face landmarks are more pronounced in age groups per ancestry as opposed to
      differences per age and sex. Generally, an increase in STT was seen between 6-10
      year old groups and 11-13 year old groups, regardless of ancestry and sex, at the
      midphiltrum, labiale inferius, pogonion, and beneath chin landmarks. This
      research created a reference dataset for STT of South African children of Black
      and Coloured ancestry per age and sex that will be useful for facial
      reconstruction/approximation of juvenile remains. 

PMID- 25998716
TI  - The emerging complexity of gene fusions in cancer.
AB  - Structural chromosome rearrangements may result in the exchange of coding or
      regulatory DNA sequences between genes. Many such gene fusions are strong driver
      mutations in neoplasia and have provided fundamental insights into the disease
      mechanisms that are involved in tumorigenesis. The close association between the
      type of gene fusion and the tumour phenotype makes gene fusions ideal for
      diagnostic purposes, enabling the subclassification of otherwise seemingly
      identical disease entities. In addition, many gene fusions add important
      information for risk stratification, and increasing numbers of chimeric proteins
      encoded by the gene fusions serve as specific targets for treatment, resulting in
      dramatically improved patient outcomes. In this Timeline article, we describe the
      spectrum of gene fusions in cancer and how the methods to identify them have
      evolved, and also discuss conceptual implications of current, sequencing-based
      approaches for detection. 

PMID- 25998721
TI  - Effects of ozone pretreatment on viability of random pattern skin flaps in rats.
AB  - BACKGROUND: Medical ozone is a chemical agent that consists of three oxygen atoms
      and has antioxidant, angiogenic and vasodilator effects. This study evaluated the
      effects of medical ozone pre-treatment on flap survival. MATERIALS AND METHODS:
      Rats were divided into four groups of 10 rats each and a 9 * 3 cm McFarlane flap
      was used. Sham group: Neither surgical nor ozone pretreatment was used. CONTROL
      GROUP: No pretreatment was used after surgery. Preoperative ozone group:
      Preoperative 1 mg/kg ozone was given intraperitoneally for 7 days. No
      pretreatment was used after surgery. Postoperative ozone Group: Postoperative 1
      mg/kg ozone was given intraperitoneally for 7 days. After postoperative 1 week,
      all groups were evaluated by surface area measurement, histopathology and
      electron microscopy. RESULTS: With the experimental McFarlane flap model, the
      experimental groups had better surface area measurements, along with
      histopathological and electron microscopic results when compared with the control
      group. CONCLUSION: Medical ozone had positive effects on flap survival due to its
      antioxidant, angiogenic and vasodilator qualities.

PMID- 25998720
TI  - Differences in biomechanical properties and thickness among frontal and parietal
      bones in a Japanese sample.
AB  - The aim of this study was to assess the mechanical properties and thickness of
      adult frontal and parietal bones. The heads of 114 Japanese cadavers (78 male
      cadavers and 36 female cadavers) of known age and sex were used. A total of 912
      cranial samples, 8 from each skull, were collected. Samples were imaged using
      multidetector computed tomography to measure sample thickness. The fracture load
      of each sample was measured using a bending test with calculation of flexural
      strength. Statistical analyses demonstrated no significant bilateral difference
      in either the mechanical properties or thickness of frontal or parietal bones.
      The mechanical properties and thicknesses of frontal bones were significantly
      greater than those of parietal bones regardless of sex. Therefore, the skull may
      have a great ability to resist frontal impacts compared with parietal impacts. In
      female samples, parietal bones were found to have a more uniform structure when
      compared with male samples. Male parietal bones were found to be thicker at
      medial sites than at lateral sites. This study also revealed parietal bones at
      lateral sites in female samples were thicker than in male samples. No strong
      association was observed between age and flexural strength of frontal or parietal
      bones. However, the fracture load was negatively correlated with age most likely
      due to the reduction of thickness. 

PMID- 25998722
TI  - Deep Brain Stimulation in the Setting of Cochlear Implants: Case Report and
      Literature Review.
AB  - BACKGROUND/AIMS: As technology continues to advance for our aging population, an
      increasing number of deep brain stimulation (DBS) candidates will have
      preexisting implanted electrical devices. In this article, we discuss safe and
      successful DBS in a patient with Parkinson's disease (PD) and bilateral cochlear
      implants. METHODS: A 70-year-old male with PD and bilateral cochlear implants
      underwent successful microelectrode-guided DBS implantation into bilateral
      subthalamic nuclei (STN). The patient's cochlear implant magnets were removed and
      replaced in the outpatient clinic for preoperative MRI and stereotactic
      targeting. The cochlear implants were turned off intraoperatively for STN
      microelectrode recordings. RESULTS: Precise, MRI-guided stereotactic DBS
      implantation was possible. Intraoperative high-fidelity microelectrode recordings
      confirmed STN neurons with the cochlear implants turned off. These recordings
      were not possible with active cochlear implant devices. Our literature review
      describes the other approaches/techniques that have been used to manage DBS
      surgery in the setting of cochlear implants. CONCLUSIONS: Despite the risk of
      electrical interference between implanted medical devices, DBS and cochlear
      implants may be safe and compatible in the same patient if necessary precautions
      are taken.

PMID- 25998723
TI  - Neutrophil migration under spatially-varying chemoattractant gradient profiles.
AB  - Chemotaxis plays an important role in biological processes such as cancer
      metastasis, embryogenesis, wound healing, and immune response. Neutrophils are
      the frontline defenders against invasion of foreign microorganisms into our
      bodies. To achieve this important immune function, a neutrophil can sense minute
      chemoattractant concentration differences across its cell body and effectively
      migrate toward the chemoattractant source. Furthermore, it has been demonstrated
      in various studies that neutrophils are highly sensitive to changes in the
      surrounding chemoattractant environments, suggesting the role of a chemotactic
      memory for processing the complex spatiotemporal chemical guiding signals. Using
      a microfluidic device, in the present study we characterized neutrophil migration
      under spatially varying profiles of interleukine-8 gradients, which consist of
      three spatially ordered regions of a shallow gradient, a steep gradient and a
      nearly saturated gradient. This design allowed us to examine how neutrophils
      migrate under different chemoattractant gradient profiles, and how the migratory
      response is affected when the cell moves from one gradient profile to another in
      a single experiment. Our results show robust neutrophil chemotaxis in the shallow
      and steep gradient, but not the saturated gradient. Furthermore, neutrophils
      display a transition from chemotaxis to flowtaxis when they migrate across the
      steep gradient interface, and the relative efficiency of this transition depends
      on the cell's chemotaxis history. Finally, some neutrophils were observed to
      adjust their morphology to different gradient profiles. 

PMID- 25998724
TI  - The English Channel and its catchments: Status and responses to contaminants.

PMID- 25998725
TI  - Unravelling the role of zooxanthellae in the uptake and depuration of an
      essential metal in Exaiptasia pallida; an experiment using a model cnidarian.
AB  - Coral skeletons record historical trace metal levels in the environment, however,
      the use of coral skeletal records for biomonitoring studies mostly fail to
      consider the influence of metal regulation by the living components of coral and
      subsequent incorporation into the skeleton. This study presents Exaiptasia
      pallida as a representative of the living components of coral and shows metal
      partitioning between the tissue and zooxanthellae after chronic exposure to Zn. A
      strong tendency for preferential accumulation in the zooxanthellae occurred after
      32 days exposure and Zn concentrations in tissue and zooxanthellae were 123.3+/
      0.7 mg kg(-1) and 294.9+/-8.5 respectively. This study shows zooxanthellae
      density plays an important role in controlling Zn loading in whole anemones and
      must be considered when investigating metal uptake and loading in zooxanthellate
      organisms. Further studies that investigate links between aragonite deposition
      rates and zooxanthellae density and incorporation pathways of metals into
      skeleton are warranted.

PMID- 25998726
TI  - Occurrence of pharmaceutical compounds and pesticides in aquatic systems.
AB  - This paper deals with the detection and quantification of APIs and other priority
      substances in the Arade River estuary (Portugal) providing the usefulness of
      Polar Organic Compound Integrative Samplers (POCIS). Thirteen APIs were detected
      whose variation was site and time dependent. Caffeine was at the highest
      concentration (804+/-209 ng/L) followed by theophylline (184+/-44 ng/L). Other
      APIs were analgesic, anticonvulsant, non-steroidal anti-inflammatory drugs, anti
      lipidemic, anxiolytic and antidepressants. Twenty pesticides comprising atrazine,
      diuron, isoproturon, terbutryn and simazine included in the Water Framework
      Directive priority list were also site and time dependent. Carbendazim occurred
      at the highest concentration (45+/-18 ng/L at site 1) but atrazine, diuron,
      isoproturon and simazine levels were below the Environmental Quality Standards.
      Although the summer impact was unclear, the results highlighted POCIS suitability
      for profiling these contaminants. This is to our knowledge the first study
      concerning APIs and pesticides in this area.

PMID- 25998727
TI  - Litter and seabirds found across a longitudinal gradient in the South Pacific
      Ocean.
AB  - Abundances and composition of marine litter and seabirds were estimated in the
      central South Pacific (SP) Ocean between the Chilean continental coast and the
      Easter Island Ecoregion. Litter was dominated by plastics throughout the study
      area, but the proportion of plastics was higher at sea and on the oceanic islands
      than in coastal waters and on continental beaches. Litter densities were higher
      close to the center of the SP subtropical gyre compared to the continental coast.
      The seabird assemblage was diverse (28 species), and several endemic species were
      recorded. Seabird abundances were higher in the coastal waters and around Juan
      Fernandez Islands off the continental coast than in the Oceanic and Polynesian
      sectors. Endangered species breeding on Salas & Gomez Island were observed in the
      Polynesian sector, which suggests a high potential for negative interactions
      between seabirds and floating litter, both occurring in high densities in this
      sector. 

PMID- 25998728
TI  - Ernesto Carafoli: A personal appreciation.

PMID- 25998729
TI  - Calmodulin and STIM proteins: Two major calcium sensors in the cytoplasm and
      endoplasmic reticulum.
AB  - The calcium (Ca(2+)) ion is a universal signalling messenger which plays vital
      physiological roles in all eukaryotes. To decode highly regulated intracellular
      Ca(2+) signals, cells have evolved a number of sensor proteins that are ideally
      adapted to respond to a specific range of Ca(2+) levels. Among many such
      proteins, calmodulin (CaM) is a multi-functional cytoplasmic Ca(2+) sensor with a
      remarkable ability to interact with and regulate a plethora of structurally
      diverse target proteins. CaM achieves this 'multi-talented' functionality through
      two EF-hand domains, each with an independent capacity to bind targets, and an
      adaptable flexible linker. By contrast, stromal interaction molecule-1 and -2
      (STIMs) have evolved for a specific role in endoplasmic reticulum (ER) Ca(2+)
      sensing using EF-hand machinery analogous to CaM; however, whereas CaM
      structurally adjusts to dissimilar binding partners, STIMs use the EF-hand
      machinery to self-regulate the stability of the Ca(2+) sensing domain. The
      molecular mechanisms underlying the Ca(2+)-dependent signal transduction by CaM
      and STIMs have revealed a remarkable repertoire of actions and underscore the
      flexibility of nature in molecular evolution and adaption to discrete Ca(2+)
      levels. Recent genomic sequencing efforts have uncovered a number of disease
      associated mutations in both CaM and STIM1. This article aims to highlight the
      most recent key structural and functional findings in the CaM and STIM fields,
      and discusses how these two Ca(2+) sensor proteins execute their biological
      functions. 

PMID- 25998730
TI  - Forcing open TRP channels: Mechanical gating as a unifying activation mechanism.
AB  - Transient receptor potential (TRP) proteins are cation channels that comprise a
      superfamily of molecular sensors that enable animals to detect a wide variety of
      environmental stimuli. This versatility enables vertebrate and invertebrate TRP
      channels to function in a diversity of senses, ranging from vision to taste,
      smell, touch, hearing, proprioception and thermosensation. Moreover, many
      individual TRP channels are activated through a surprising range of sensory
      stimuli. The multitasking nature of TRP channels raises the question as to
      whether seemingly disparate activators gate TRPs through common strategies. In
      this regard, a recent major advance is the discovery that a phospholipase C (PLC)
      dependent signaling cascade activates the TRP channels in Drosophila
      photoreceptor cells through generation of force in the lipid-bilayer. The premise
      of this review is that mechanical force is a unifying, common strategy for gating
      TRP channels. In addition to several TRP channels that function in
      mechanosensation and are gated by force applied to the cells, changes in
      temperature or alterations in the concentration of lipophilic second messengers
      through stimulation of signaling cascades, cause architectural modifications of
      the cell membrane, which in turn activate TRP channels through mechanical force.
      Consequently, TRPs are capable of functioning as stretch-activated channels, even
      in cases in which the stimuli that initiate the signaling cascades are not
      mechanical. We propose that most TRPs are actually mechanosensitive channels
      (MSCs), which undergo conformational changes in response to tension imposed on
      the lipid bilayer, resulting in channel gating. 

PMID- 25998731
TI  - Plasma membrane calcium ATPases: From generic Ca(2+) sump pumps to versatile
      systems for fine-tuning cellular Ca(2.).
AB  - The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps
      found in all eukaryotic cells. They are the major high-affinity calcium extrusion
      system for expulsion of Ca(2+) ions from the cytosol and help restore the low
      resting levels of intracellular [Ca(2+)] following the temporary elevation of
      Ca(2+) generated during Ca(2+) signaling. Due to their essential role in the
      maintenance of cellular Ca(2+) homeostasis they were initially thought to be
      "sump pumps" for Ca(2+) removal needed by all cells to avoid eventual calcium
      overload. The discovery of multiple PMCA isoforms and alternatively spliced
      variants cast doubt on this simplistic assumption, and revealed instead that
      PMCAs are integral components of highly regulated multi-protein complexes
      fulfilling specific roles in calcium-dependent signaling originating at the
      plasma membrane. Biochemical, genetic, and physiological studies in gene
      manipulated and mutant animals demonstrate the important role played by specific
      PMCAs in distinct diseases including those affecting the peripheral and central
      nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene
      mutations and allelic variants associated with specific disorders continue to be
      discovered and underline the crucial role of different PMCAs in particular cells,
      tissues and organs. 

PMID- 25998733
TI  - Standing of giants shoulders the story of the mitochondrial Na(+)Ca(2+)
      exchanger.
AB  - It is now the 40th anniversary of the Journal of Molecular and Cellular
      Cardiology paper by Ernesto Carafoli and colleagues. This seminal study described
      for the first time mitochondrial Ca(2+) extrusion and its coupling to Na(+). This
      short review will describe the profound impact that this work had on
      mitochondrial signaling and the cross talk between the mitochondria, the ER, and
      the plasma membrane. It will further tell how the functional identification and
      in particular its unique cation selectivity to both Li(+) and Na(+) eventually
      contributed to the identification of the mitochondrial Na(+)/Ca(2+) exchanger
      gene NCLX many years later. The last part will describe how molecular tools
      derived from NCLX identification are used to study the novel physiological
      aspects of Ca(2+) signaling. 

PMID- 25998735
TI  - Calcium and mitochondria in the regulation of cell death.
AB  - The calcium ion has long been known to play an important role in cell death
      regulation. Hence, necrotic cell death was early associated with intracellular
      Ca(2+) overload, leading to mitochondrial permeability transition and functional
      collapse. Subsequent characterization of the signaling pathways in apoptosis
      revealed that Ca(2+)/calpain was critically involved in the processing of the
      mitochondrially localized, Apoptosis Inducing Factor. More recently, the calcium
      ion has been demonstrated to play important regulatory roles also in other cell
      death modalities, notably autophagic cell death and anoikis. In this review, we
      summarize current knowledge about the mechanisms involved in Ca(2+) regulation of
      these various modes of cell death with a focus on the importance of the
      mitochondria. 

PMID- 25998734
TI  - Vitamin D cell signalling in health and disease.
AB  - Vitamin D deficiency has been linked to many human diseases such as Alzheimer's
      disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), hypertension and
      cardiovascular disease. A Vitamin D phenotypic stability hypothesis, which is
      developed in this review, attempts to describe how this vital hormone acts to
      maintain healthy cellular functions. This role of Vitamin D as a guardian of
      phenotypic stability seems to depend on its ability to maintain the redox and
      Ca(2+) signalling systems. It is argued that its primary action is to maintain
      the expression of those signalling components responsible for stabilizing the low
      resting state of these two signalling pathways. This phenotypic stability role is
      facilitated through the ability of vitamin D to increase the expression of both
      Nrf2 and the anti-ageing protein Klotho, which are also major regulators of
      Ca(2+) and redox signalling. A decline in Vitamin D levels will lead to a decline
      in the stability of this regulatory signalling network and may account for why so
      many of the major diseases in man, which have been linked to vitamin D
      deficiency, are associated with a dysregulation in both ROS and Ca(2+)
      signalling. 

PMID- 25998732
TI  - Store-operated calcium entry: Mechanisms and modulation.
AB  - Store-operated calcium entry is a central mechanism in cellular calcium
      signalling and in maintaining cellular calcium balance. This review traces the
      history of research on store-operated calcium entry, the discovery of STIM and
      ORAI as central players in calcium entry, and the role of STIM and ORAI in
      biology and human disease. It describes current knowledge of the basic mechanism
      of STIM-ORAI signalling and of the varied mechanisms by which STIM-ORAI
      signalling can be modulated. 

PMID- 25998736
TI  - Apoptosis induction-related cytosolic calcium responses revealed by the dual FRET
      imaging of calcium signals and caspase-3 activation in a single cell.
AB  - Stimulus-induced changes in the intracellular Ca(2+) concentration control cell
      fate decision, including apoptosis. However, the precise patterns of the
      cytosolic Ca(2+) signals that are associated with apoptotic induction remain
      unknown. We have developed a novel genetically encoded sensor of activated
      caspase-3 that can be applied in combination with a genetically encoded sensor of
      the Ca(2+) concentration and have established a dual imaging system that enables
      the imaging of both cytosolic Ca(2+) signals and caspase-3 activation, which is
      an indicator of apoptosis, in the same cell. Using this system, we identified
      differences in the cytosolic Ca(2+) signals of apoptotic and surviving DT40 B
      lymphocytes after B cell receptor (BCR) stimulation. In surviving cells, BCR
      stimulation evoked larger initial Ca(2+) spikes followed by a larger sustained
      elevation of the Ca(2+) concentration than those in apoptotic cells; BCR
      stimulation also resulted in repetitive transient Ca(2+) spikes, which were
      mediated by the influx of Ca(2+) from the extracellular space. Our results
      indicate that the observation of both Ca(2+) signals and cells fate in same cell
      is crucial to gain an accurate understanding of the function of intracellular
      Ca(2+) signals in apoptotic induction. 

PMID- 25998738
TI  - Regulation of Parvalbumin Basket cell plasticity in rule learning.
AB  - Local inhibitory Parvalbumin (PV)-expressing Basket cell networks shift to one of
      two possible opposite configurations depending on whether behavioral learning
      involves acquisition of new information or consolidation of validated rules. This
      reflects the existence of PV Basket cell subpopulations with distinct schedules
      of neurogenesis, output target neurons and roles in learning. Plasticity of
      hippocampal early-born PV neurons is recruited in rule consolidation, whereas
      plasticity of late-born PV neurons is recruited in new information acquisition.
      This involves regulation of early-born PV neuron plasticity specifically through
      excitation, and of late-born PV neuron plasticity specifically through
      inhibition. Therefore, opposite learning requirements are implemented by distinct
      local networks involving PV Basket cell subpopulations specifically regulated
      through inhibition or excitation. 

PMID- 25998737
TI  - Evolutionary and functional perspectives on signaling from neuronal surface to
      nucleus.
AB  - Reliance on Ca(2+) signaling has been well-preserved through the course of
      evolution. While the complexity of Ca(2+) signaling pathways has increased,
      activation of transcription factors including CREB by Ca(2+)/CaM-dependent
      kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans,
      the CaMK family is made up of only three members, and CREB phosphorylation is
      mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly
      regulates adaptation of thermotaxis behavior in response to changes in the
      environment. In mammals, the CaMK family has been expanded from three to ten
      members, enabling specialization of individual elements of a signal transduction
      pathway and increased reliance on the CaMKII subfamily. This increased complexity
      enables private line communication between Ca(2+) sources at the cell surface and
      specific cellular targets. Using both new and previously published data, we
      review the mechanism of a gammaCaMKII-CaM nuclear translocation. This intricate
      pathway depends on a specific role for multiple Ca(2+)/CaM-dependent kinases and
      phosphatases: alpha/betaCaMKII phosphorylates gammaCaMKII to trap CaM; CaN
      dephosphorylates gammaCaMKII to dispatch it to the nucleus; and PP2A induces CaM
      release from gammaCaMKII so that CaMKK and CaMKIV can trigger CREB
      phosphorylation. Thus, while certain basic elements have been conserved from C.
      elegans, evolutionary modifications offer opportunities for targeted
      communication, regulation of key nodes and checkpoints, and greater specificity
      and flexibility in signaling. 

PMID- 25998739
TI  - Calcium and actin in the saga of awakening oocytes.
AB  - The interaction of the spermatozoon with the egg at fertilization remains one of
      the most fascinating mysteries of life. Much of our scientific knowledge on
      fertilization comes from studies on sea urchin and starfish, which provide plenty
      of gametes. Large and transparent, these eggs have served as excellent model
      systems for studying egg activation and embryo development in seawater, a plain
      natural medium. Starfish oocytes allow the study of the cortical, cytoplasmic and
      nuclear changes during the meiotic maturation process, which can also be
      triggered in vitro by hormonal stimulation. These morphological and biochemical
      changes ensure successful fertilization of the eggs at the first metaphase. On
      the other hand, sea urchin eggs are fertilized after the completion of meiosis,
      and are particularly suitable for the study of sperm-egg interaction, early
      events of egg activation, and embryonic development, as a large number of mature
      eggs can be fertilized synchronously. Starfish and sea urchin eggs undergo abrupt
      changes in the cytoskeleton and ion fluxes in response to the fertilizing
      spermatozoon. The plasma membrane and cortex of an egg thus represent "excitable
      media" that quickly respond to the stimulus with the Ca(2+) swings and structural
      changes. In this article, we review some of the key findings on the rapid dynamic
      rearrangements of the actin cytoskeleton in the oocyte/egg cortex upon hormonal
      or sperm stimulation and their roles in the modulation of the Ca(2+) signals and
      in the control of monospermic fertilization. 

PMID- 25998740
TI  - Ca(2+) homeostasis and endoplasmic reticulum (ER) stress: An integrated view of
      calcium signaling.
AB  - Cellular Ca(2+) homeostasis is maintained through the integrated and coordinated
      function of Ca(2+) transport molecules, Ca(2+) buffers and sensors. These
      molecules are associated with the plasma membrane and different cellular
      compartments, such as the cytoplasm, nucleus, mitochondria, and cellular
      reticular network, including the endoplasmic reticulum (ER) to control free and
      bound Ca(2+) levels in all parts of the cell. Loss of nutrients/energy leads to
      the loss of cellular homeostasis and disruption of Ca(2+) signaling in both the
      reticular network and cytoplasmic compartments. As an integral part of cellular
      physiology and pathology, this leads to activation of ER stress coping responses,
      such as the unfolded protein response (UPR), and mobilization of pathways to
      regain ER homeostasis. 

PMID- 25998741
TI  - Further evaluation of the high-probability instructional sequence with and
      without programmed reinforcement.
AB  - In 2 experiments, we examined the effects of programmed reinforcement for
      compliance with high-probability (high-p) instructions on compliance with low
      probability (low-p) instructions. In Experiment 1, we compared the high-p
      sequence with and without programmed reinforcement (i.e., edible items) for
      compliance with high-p instructions. Results showed that the high-p sequence
      increased compliance with low-p instructions only when compliance with high-p
      instructions was followed by reinforcement. In Experiment 2, we examined the role
      of reinforcer quality by delivering a lower quality reinforcer (praise) for
      compliance with high-p instructions. Results of Experiment 2 showed that the high
      p sequence with lower quality reinforcement did not improve compliance with low-p
      instructions; the addition of a higher quality reinforcer (i.e., edible items)
      contingent on compliance with high-p instructions did increase compliance with
      low-p instructions. 

PMID- 25998742
TI  - Rhabdomyolys is owing to a wasp sting.

PMID- 25998743
TI  - The determinants of efficiency in the Canadian health care system.
AB  - In spite of the vast number of studies measuring economic efficiency in health
      care, there has been little take-up of this evidence by policy-makers to date.
      This study provides an illustration of how a system-level study drawing on best
      practice in empirical measurement of efficiency may be of practical use to health
      system decision makers and managers. We make use of the rich data available in
      Canada to undertake a robust two-stage data envelopment analysis to calculate
      efficiency at the regional (sub-provincial) level. Decisions about what the
      health system produces (the outcome to measure efficiency against) and what are
      the resources it has to produce that outcome were based on interviews and
      consultation with health system decision makers. Overall, we find large
      inefficiencies in the Canadian health care system, which could improve outcomes
      (here, measured as a reduction in treatable causes of death) by between 18 and
      35% across our analyses. Also, we find that inefficiencies are the result of
      three main sets of factors that policy makers could pay attention to: management
      factors, such as hospital re-admissions; public health factors, such as obesity
      and smoking rates; and environmental factors such as the population's average
      income. 

PMID- 25998744
TI  - Bilateral spontaneous aqueous misdirection: it can happen!

PMID- 25998745
TI  - Daintain/AIF-1 accelerates the activation of insulin-like growth factor-1
      receptor signaling pathway in HepG2 cells.
AB  - Daintain/allograft inflammatory factor-1 (AIF-1), as a novel inflammatory factor,
      has been reported to accelerate the proliferation and migration of breast cancer
      cells. However, the effect of daintain/AIF-1 on hepatocarcinogenesis remains
      unclear. In order to explore the effect of daintain/AIF-1 on the progression of
      hepatocellular carcinoma (HCC), enzyme-linked immunosorbent assay (ELISA) and
      reverse transcription polymerase chain reaction (RT-PCR) were performed to
      examine the secretion and gene expression of (IGF)-1, IGF-2 and IGFBP-3. The
      expression of IGF-1R and its downstream targets was evaluated by western
      blotting. In addition, the proliferation and cell-cycle progression of HepG2
      cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide
      (MTT) and flow cytometric analysis. The results showed that HepG2 cells subjected
      to daintain/AIF-1 treatment revealed an obvious increase in the secretion of IGF
      1 and IGF-2, and a reduction in the secretion of IGFBP-3. Moreover, daintain/AIF
      1 accelerated the activation of IGF-1-induced IGF-1R and its downstream AKT
      signaling pathway, and subsequently promoted the activation of cyclin D1 pathway,
      thus accelerating the progression of the cell cycle and eventually promoting the
      proliferation of HepG2 cells. In conclusion, daintain/AIF-1 promoted the
      proliferation of HepG2 cells by accelerating the activation of IGF-1R and its
      downstream signaling pathway, which confirms that daintain/AIF-1 plays a crucial
      role in the development of HCC.

PMID- 25998746
TI  - Agent Orange and long-term outcomes after radical prostatectomy.
AB  - PURPOSE: To investigate the association between Agent Orange (AO) exposure and
      long-term prostate cancer (PC) outcomes. MATERIAL AND METHODS: Data from 1,882
      men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans
      Affairs Health Care Facilities were analyzed from the Shared Equal Access
      Regional Cancer Hospital database. Men were stratified by AO exposure (binary).
      Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and
      pathologic stage were determined by logistic regression models adjusted for
      preoperative characteristics. Hazard ratios for biochemical recurrence (BCR),
      secondary treatment, metastases, and PC-specific mortality were determined by Cox
      models adjusted for preoperative characteristics. RESULTS: There were 333 (17.7%)
      men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower
      preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical
      category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6
      kg/m(2)), all P<0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph
      node positivity, and extracapsular extension did not differ with AO exposure. At
      a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%)
      patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%)
      died of PC. On multivariable analysis, AO exposure was not associated with BCR,
      secondary treatment, metastases, or PC mortality. CONCLUSIONS: AO exposure was
      not associated with worse preoperative characteristics such as elevated prostate
      specific antigen levels or biopsy GS nor with BCR, secondary treatment,
      metastases, or PC death. Thus, as data on AO-exposed men mature, possible
      differences in PC outcomes observed previously are no longer apparent.

PMID- 25998747
TI  - Influence of pathological factors on oncological outcomes after robot-assisted
      radical prostatectomy for localized prostate cancer: Results of a prospective
      study.
AB  - PURPOSE: To assess the prognostic significance of lymphovascular invasion (LVI),
      maximum tumor diameter (MTD), high-grade prostatic intraepithelial neoplasia,
      perineural invasion, and length of positive surgical margins after robot-assisted
      radical prostatectomy (RARP). METHODS: A single-institution prospective analysis
      of all patients who underwent RARP for localized prostate cancer was performed
      between January 2005 and June 2013. The primary end point was biochemical
      recurrence-free survival (BRFS). BRFS was estimated using the Kaplan-Meier method
      and compared to that from the log-rank test. Cox's proportional hazards
      regression univariate and multivariate analyses were performed to define the
      prognostic factors. RESULTS: Overall, 742 men were included. After a median
      follow-up of 31.4 months, biochemical recurrence occurred in 80 patients (10.8%).
      BRFS was 93%, 87%, and 80.7% at 1, 3, and 5 years, respectively. Progression to
      local recurrence occurred in 49 patients (6.6%). During the follow-up period, 3
      patients experienced progression to metastatic disease and were treated with
      hormonotherapy. No patient died of disease during the study period. In
      multivariate analyses, Gleason score was the strongest predictor of BRFS (hazard
      ratio [HR] = 3.4; P<0.001). There were 3 other predictive factors of BRFS were
      LVI (HR = 7.64; P = 0.005), MTD (HR = 4.04; P =0.009), and margin length >= 3 mm
      (HR = 1.25; P = 0.04). CONCLUSION: In the era of serum prostate-specific antigen
      testing maturity in conjunction with a single approach to extirpation of the
      prostate gland by RARP, LVI, MTD, and positive surgical margins >= 3 mm are
      prognostic factors associated with BRFS after RARP. Consideration could be given
      to incorporate them in the pathology report of the radical prostatectomy
      specimens and they could assist physicians in clinical decision making.

PMID- 25998748
TI  - Two WUSCHEL-related HOMEOBOX genes, PeWOX11a and PeWOX11b, are involved in
      adventitious root formation of poplar.
AB  - The plant-specific WUSCHEL-related HOMEOBOX (WOX) transcription factors play
      important roles in key developmental processes, but knowledge regarding
      functional characterization of WOX genes in poplar remains limited. To reveal
      genes and signaling pathways associated with adventitious rooting in poplar, here
      we isolated and characterized two WOX genes through the rapid amplification of
      cDNA ends (RACE), sequence aligning, expression profiling, protoplast
      transfection and poplar transformation. Detailed information about the sequence
      similarity, structural features, evolutionary relationships, expression patterns
      and subcellular localization of the two genes were revealed. Overexpression of
      either PeWOX11a or PeWOX11b not only increased the number of adventitious roots
      on the cuttings but also induced ectopic roots in the aerial parts of transgenic
      poplars. Meanwhile, their overexpression in transgenic poplars affected axillary
      bud and leaf development. These results suggest that PeWOX11a and PeWOX11b were
      involved in multiple developmental processes of poplar, especially in
      adventitious root formation. Our results provide new insights into the molecular
      mechanisms underlying adventitious root formation of poplar. 

PMID- 25998749
TI  - Autosomal recessive congenital ichthyoses in the Czech Republic.

PMID- 25998750
TI  - Reply to Commentary on "Neural correlates of mirth and laughter: A direct
      electrical cortical stimulation study".

PMID- 25998751
TI  - Effects of configural processing on the perceptual spatial resolution for face
      features.
AB  - Configural processing governs human perception across various domains, including
      face perception. An established marker of configural face perception is the face
      inversion effect, in which performance is typically better for upright compared
      to inverted faces. In two experiments, we tested whether configural processing
      could influence basic visual abilities such as perceptual spatial resolution
      (i.e., the ability to detect spatial visual changes). Face-related perceptual
      spatial resolution was assessed by measuring the just noticeable difference (JND)
      to subtle positional changes between specific features in upright and inverted
      faces. The results revealed robust inversion effect for spatial sensitivity to
      configural-based changes, such as the distance between the mouth and the nose, or
      the distance between the eyes and the nose. Critically, spatial resolution for
      face features within the region of the eyes (e.g., the interocular distance
      between the eyes) was not affected by inversion, suggesting that the eye region
      operates as a separate 'gestalt' unit which is relatively immune to manipulations
      that would normally hamper configural processing. Together these findings suggest
      that face orientation modulates fundamental psychophysical abilities including
      spatial resolution. Furthermore, they indicate that classic psychophysical
      methods can be used as a valid measure of configural face processing. 

PMID- 25998752
TI  - The Presence of Intra- or Subretinal Fluid during the Loading Phase in the
      Treatment of Exudative Age-Related Macular Degeneration with Intravitreal
      Ranibizumab Assessed by Optical Coherence Tomography.
AB  - PURPOSE: To assess intra- and subretinal fluid during the loading phase with
      intravitreal ranibizumab in exudative age-related macular degeneration and to
      quantify the accuracy of crosshair scan spectral-domain optical coherence
      tomography with regard to retinal fluid. METHODS: This is a retrospective study
      of 31 treatment-naive patients who received 3 monthly intravitreal ranibizumab
      injections. Visual acuity and the presence of retinal fluid were assessed at each
      visit using volume and crosshair scan protocols. RESULTS: Visual acuity improved
      and central retinal thickness decreased significantly during the loading phase.
      However, retinal fluid persisted in two thirds of the patients. The accuracy of
      the crosshair scan to detect fluid was 93%. CONCLUSIONS: A substantial proportion
      of eyes had persistent fluid after 3 months of ranibizumab injections. However,
      visual improvement was independent of residual fluid. MESSAGE: Crosshair scans
      detect relevant collections of retinal fluid accurately and may be sufficient in
      daily clinical practice.

PMID- 25998753
TI  - Up-regulation of calcitonin gene-related peptide in trigeminal ganglion following
      chronic exposure to paracetamol in a CSD migraine animal model.
AB  - Previously, our group has demonstrated that chronic paracetamol (APAP) treatment
      induces alterations to the trigeminovascular nociceptive system in the cortical
      spreading depression (CSD) migraine animal model. The calcitonin gene related
      peptide (CGRP) is a key neuropeptide involved in the activation of the
      trigeminovascular nociceptive system. Therefore, this study examined the
      expression levels of CGRP in the trigeminal ganglion (TG) after chronic APAP
      exposure (0, 15, and 30 days) using a CSD model. Rats were divided into control,
      CSD only, APAP only and APAP treatment with CSD groups. A single injection (i.p.)
      of APAP (200 mg/kg body weight) was given to the 0-day APAP-treated groups, while
      the other APAP-treated groups received daily injections for 15 and 30 days. CSD
      was induced by the topical application of KCl to the parietal cortex. The protein
      expression of CGRP in the TG was evaluated by immunohistochemistry, and the CGRP
      mRNA level was investigated by real-time quantitative reverse transcription
      polymerase chain reaction. The results revealed that the induction of CSD
      significantly increased the level of CGRP protein but had no effect on CGRP mRNA
      level. Pretreatment with APAP 1 hour before CSD activation significantly reduced
      CGRP expression induced by CSD. In contrast, chronic treatment with APAP (15 and
      30 days) significantly enhanced CGRP expression in both protein and mRNA levels
      when compared with the control groups. In combination with CSD, the expression of
      CGRP further increased in the animal with 30 day treatment. These findings
      indicate that chronic treatment with APAP induces an increase of CGRP expression
      in the TG. This alteration may be associated with the increased trigeminovascular
      nociception observed in our previous studies.

PMID- 25998754
TI  - Platelet Function Testing and Prediction of Bleeding in Patients Exposed to
      Clopidogrel Undergoing Coronary Artery Surgery.

PMID- 25998755
TI  - Heat-sensitive moxibustion in patients with osteoarthritis of the knee: a three
      armed multicentre randomised active control trial.
AB  - BACKGROUND: In China, heat-sensitive moxibustion (HSM) is used for knee
      osteoarthritis (KOA) to reduce pain and improve physical activity. However, there
      is little high-quality evidence of its effectiveness. OBJECTIVE: To evaluate the
      effectiveness of HSM in the treatment of KOA compared with usual care. METHODS:
      We performed a multicentre, randomised controlled trial. In total, 432 patients
      with KOA were randomly assigned to one of three groups (HSM, conventional
      moxibustion, or conventional injection with sodium hyaluronate). The primary end
      point was the guiding principle of clinical research on new drugs in the
      treatment of KOA (GPCRND-KOA). Measurements were obtained at baseline and after 1
      and 6 months (month 7) of study. RESULT: For GPCRND-KOA, there were significant
      differences among the three groups after treatment at months 1 and 7. Pairwise
      comparisons showed that HSM was more effective than the conventional drug. There
      was no difference in any measures between conventional moxibustion and the
      conventional drug. Compared with conventional moxibustion, HSM resulted in
      greater improvement in all outcomes. CONCLUSIONS: This trial provided some
      evidence of the superiority of HSM in patients with KOA, suggesting that the
      observed differences might be due to superiority effects of a heat-sensitive
      point, although the effect of expectation cannot be ruled out. TRIAL REGISTRATION
      NUMBER: The trial was registered at Controlled Clinical Trials: ChiCTR-TRC
      09000600.

PMID- 25998757
TI  - New president for BVA Scottish Branch.

PMID- 25998756
TI  - Celebrating animal health and welfare successes in Scotland.

PMID- 25998758
TI  - VMD enhances its antimicrobial resistance surveillance.

PMID- 25998760
TI  - Spotlight on outstanding veterinary staff and practices.

PMID- 25998759
TI  - New requirements for animal welfare officers.

PMID- 25998761
TI  - Signing up to end animal pain.

PMID- 25998762
TI  - Disciplinary committee dismisses insurance fraud case.

PMID- 25998763
TI  - Assessing rhino reproductive health.

PMID- 25998764
TI  - Collaboration on One Health: starting with students.

PMID- 25998765
TI  - Northern Ireland disease surveillance report, January to March 2015.

PMID- 25998766
TI  - Can you measure the impact of your research?

PMID- 25998767
TI  - TB control strategy.

PMID- 25998768
TI  - 'Recognised veterinary practice' in the context of clinical field trials.

PMID- 25998769
TI  - EU membership.

PMID- 25998777
TI  - Working in government service.

PMID- 25998778
TI  - Excitonic resonances in thin films of WSe2: from monolayer to bulk material.
AB  - We present optical spectroscopy (photoluminescence and reflectance) studies of
      thin layers of the transition metal dichalcogenide WSe2, with thickness ranging
      from mono- to tetra-layer and in the bulk limit. The investigated spectra show
      the evolution of excitonic resonances as a function of layer thickness, due to
      changes in the band structure and, importantly, due to modifications of the
      strength of Coulomb interactions as well. The observed temperature-activated
      energy shift and broadening of the fundamental direct exciton are well accounted
      for by standard formalisms used for conventional semiconductors. A large increase
      of the photoluminescence yield with temperature is observed in a WSe2 monolayer,
      indicating the existence of competing radiative channels. The observation of
      absorption-type resonances due to both neutral and charged excitons in the WSe2
      monolayer is reported and the effect of the transfer of oscillator strength from
      charged to neutral excitons upon an increase of temperature is demonstrated. 

PMID- 25998779
TI  - Interstitial lung disease preceding primary biliary cirrhosis in a male patient.
AB  - A 47-year-old male was admitted with subacute onset of dry cough and fever. Chest
      tomography demonstrated multifocal areas of consolidation and ground glass
      attenuation. Cytological analysis of bronchoalveolar lavage revealed
      lymphocytosis and eosinophilia and anatomopathological exam of transbronchial
      cryobiopsy showed poorly formed non-caseous granulomas associated to interstitial
      lympho-plasmocitary infiltrate. The diagnosis of idiopathic granulomatous lung
      disease (GLD) was assumed and the patient started oral prednisolone, presenting
      clinical, functional and radiological improvement. Two years later, the patient
      was diagnosed with primary biliary cirrhosis (PBC). At this time, it was possible
      to associate GLD with the autoimmune hepatobiliary disease. Clinical,
      epidemiological and pathological aspects of this uncommon case of interstitial
      lung disease as first presentation of PBC in a male patient are discussed. 

PMID- 25998780
TI  - Effect of field view size and lighting on unique-hue selection using Natural
      Color System object colors.
AB  - The aim of this study was twofold, first to determine the effect of field view
      size and second of illumination conditions on the selection of unique hue samples
      (UHs: R, Y, G and B) from two rotatable trays, each containing forty highly
      chromatic Natural Color System (NCS) samples, on one tray corresponding to 1.4
      degrees  and on the other to 5.7 degrees  field of view size. UH selections were
      made by 25 color-normal observers who repeated assessments three times with a gap
      of at least 24h between trials. Observers separately assessed UHs under four
      illumination conditions simulating illuminants D65, A, F2 and F11. An apparent
      hue shift (statistically significant for UR) was noted for UH selections at 5.7
      degrees  field of view compared to those at 1.4 degrees . Observers' overall
      variability was found to be higher for UH stimuli selections at the larger field
      of view. Intra-observer variability was found to be approximately 18.7% of inter
      observer variability in selection of samples for both sample sizes. The highest
      intra-observer variability was under simulated illuminant D65, followed by A,
      F11, and F2.

PMID- 25998781
TI  - A Tale of Two Cities: The Exploration of the Trieste Public Psychiatry Model in
      San Francisco.
AB  - According to the World Health Organization (WHO), the "Trieste model" of public
      psychiatry is one of the most progressive in the world. It was in Trieste, Italy,
      in the 1970s that the radical psychiatrist, Franco Basaglia, implemented his
      vision of anti-institutional, democratic psychiatry. The Trieste model put the
      suffering person-not his or her disorders-at the center of the health care
      system. The model, revolutionary in its time, began with the "negation" and
      "destruction" of the traditional mental asylum ('manicomio'). A novel community
      mental health system replaced the mental institution. To achieve this, the
      Trieste model promoted the social inclusion and full citizenship of users of
      mental health services. Trieste has been a collaborating center of the WHO for
      four decades with a goal of disseminating its practices across the world. This
      paper illustrates a recent attempt to determine whether the Trieste model could
      be translated to the city of San Francisco, California. This process revealed a
      number of obstacles to such a translation. Our hope is that a review of
      Basaglia's ideas, along with a discussion of the obstacles to their
      implementation, will facilitate efforts to foster the social integration of
      persons with mental disorders across the world. 

PMID- 25998782
TI  - Interruption of CD40 Pathway Improves Efficacy of Transplanted Endothelial
      Progenitor Cells in Monocrotaline Induced Pulmonary Arterial Hypertension.
AB  - BACKGROUND/AIMS: Transplantation of endothelial progenitor cells (EPCs) plays a
      therapeutic role in pulmonary arterial hypertension (PAH). Meanwhile, recruitment
      of progenitors has potential inflammatory effects and exaggerates vascular
      injury. CD40 pathway is identified as a major player in vascular inflammatory
      events. In this study, we investigated the role of CD40 pathway in regulating
      early outgrowth EPC functions, and searched for improvements in PAH cell therapy.
      METHODS: EPCs were isolated from rat bone marrow and cultured for 7 days. After
      treatment with soluble CD40 ligand (sCD40L) for 24 hours, EPC migration,
      adhesion, proliferation, paracrine and vasculogenesis functions were tested. Rat
      PAH model was founded by subcutaneous injection of monocrotaline (MCT). Control
      EPCs or lentivirus vectors (Lv)-shRNA-CD40 EPCs were infused via tail vein at day
      7, 14, and 21 after MCT injection. Therapeutic effects were evaluated at day 28.
      RESULTS: sCD40L dose-dependently impaired EPC migration, adhesion, proliferation,
      and vasculogenesis functions. However, paracrine effects of soluble intercellular
      adhesion molecule-1, vascular endothelial growth factor and interleukin-6 were
      dose-dependently improved by sCD40L. Control EPC-derived conditioned medium
      protected endothelial cell in vitro vasculogenesis, while sCD40L-pretreated ones
      showed detrimental effects. After MCT injection, sCD40L levels in rat serum
      increased gradually. Other than in vitro results, benefits of both two EPC
      treatments were obvious, even taken at day 21. Benefits of control EPCs wore off
      over time, but those of Lv-shRNA-CD40 EPCs were more effective and enduring, as
      characterized by both ameliorated rat hemodynamic and reversed vascular
      remodeling. Furthermore, Lv-shRNA-CD40 EPCs integrated into endothelium better,
      rather than into adventitia and media. CONCLUSION: sCD40L impaired protective
      effects of EPCs. Traditional EPC treatments were limited in PAH, while
      interruption of CD40 pathway of transplanted cells could apparently improve the
      therapeutic efficacy.

PMID- 25998783
TI  - Between personal and relational privacy: understanding the work of informed
      consent in cancer genetics in Brazil.
AB  - Drawing from perspectives of both bioethics and anthropology, this article
      explores how the boundaries between personal and relational privacy are
      negotiated by patients and practitioners in the context of an emerging domain of
      cancer genetics in Brazil. It reflects on the place of informed consent in the
      history of bioethics in North America in contrast to the development of bioethics
      in Brazil and the particular social cultural context in which consent is sought
      in Brazilian public health care. Making use of empirical research with families
      and individuals receiving genetic counselling related to increased genetic risk
      for cancer, in genetic clinics in southern Brazil, it examines how informed
      consent is linked to the necessary movement between personal and relational
      privacy. The paper illustrates the value of a particular tool known as a
      'sociogram' to examine the complex interpersonal dynamics that arise in
      negotiating informed consent at the interface between the family and the
      individual in Brazil. The paper, therefore, points to the scope of further
      interdisciplinary exchanges between anthropology and bioethics, confronting the
      new challenges that arise in the context of medical genetics in developing
      country. 

PMID- 25998784
TI  - Breast cancer in very young women: Clinicopathological study of 149 patients <=25
      years old.
AB  - BACKGROUND: Breast cancer in young women has different clinical and pathologic
      features and a more aggressive biological behavior when compared to breast
      cancers in older women. However, information is limited to the group of very
      young women (<=25 years). OBJECTIVES: The aim of the present study was to
      investigate the pathological characteristics of breast cancer in 149 Brazilian
      women who were <=25 years old at the time of breast cancer diagnosis. MATERIALS
      AND METHODS: Tumor samples diagnosed between 2003 and 2009 were analyzed from the
      archives of the Bacchi Laboratory. RESULTS: In our series of 149 Brazilian women
      <=25 years, 8.7% presented with in situ disease only. Of 136 invasive carcinomas,
      91.9% were of the ductal type and 45.6% were of histological grade III. Overall,
      estrogen receptor (ER) was positive in 59.6% cases, and HER2 overexpression was
      detected in 32.8%. We also found a low prevalence of Luminal A cases and a high
      prevalence of Triple Negative cases. Statistical analysis showed that HER2 and
      basal-like groups had a lower overall survival expectation. Follow-up data showed
      high frequencies of regional lymph node metastasis, distant metastasis, and tumor
      related deaths. CONCLUSION: The present study represents the largest series of
      breast cancer arising in women <=25 years and establishes the main clinical,
      pathological, immunohistochemical and follow-up features of this population.

PMID- 25998785
TI  - Primary Gastrointestinal Malignant Melanoma.

PMID- 25998786
TI  - Atrophic Gastritis in the Arctic.

PMID- 25998787
TI  - Cutaneous Vasculitis Caused by Anti-Tumor Necrosis Factor Therapy: A Case Report.

PMID- 25998790
TI  - Quality of Life and Quality of Support for People with Severe Intellectual
      Disability and Complex Needs.
AB  - BACKGROUND: People with severe and profound intellectual disabilities often spend
      substantial time isolated and disengaged. The nature and quality of the support
      appears to be important in determining quality of life. METHODS: Structured
      observations and staff questionnaires were used to explore the quality of life
      and quality of support for 110 people with severe and profound disabilities and
      complex needs. RESULTS: On average, people spent approximately 40% of their time
      engaged in meaningful activities, received contact from staff 25% of the time (6%
      in the form of assistance to be engaged). Just over one-third received
      consistently good active support, which was associated with other measures of
      quality of support and emerged as the strongest predictor of outcomes.
      CONCLUSIONS: Quality of life and quality of support were relatively poor,
      although with about one-third of people receiving skilled support. Consistently
      good active support was the best predictor of outcome and proposed as a good
      indicator of skilled support.

PMID- 25998788
TI  - Identification of Serum Markers of Esophageal Adenocarcinoma by Global and
      Targeted Metabolic Profiling.
AB  - BACKGROUND & AIMS: We aimed to identify new serum biomarkers of esophageal
      adenocarcinoma (EAC). METHODS: We performed metabolomic analyses of serum samples
      from 2 sets of case-control pairs in the discovery phase, each consisting of 30
      patients with histologically confirmed EAC (cases) from the University of Texas
      MD Anderson Cancer Center and 30 matched subjects without EAC (controls). We
      identified metabolites whose levels differed significantly between cases and
      controls and validated those with the greatest difference in an analysis of 321
      EAC cases and 331 controls. We generated a metabolite risk score (MRS) for the
      metabolites. RESULTS: The levels of 64 metabolites differed significantly between
      EAC cases and controls in the discovery phase. The metabolites with the greatest
      difference were amino acid L-proline (LP), ketone body 3-hydroxybutyrate (BHBA),
      and carbohydrate D-mannose (DM); these differences were confirmed in the
      validation set. Cases had lower mean levels of LP than controls (22.78 +/- 6.79
      MUg/mL vs 28.24 +/- 8.64 MUg/mL; P < .001) and higher levels of BHBA (18.06 +/-
      17.84 MUg/mL vs 7.73 +/- 9.92 MUg/mL; P < .001) and DM (9.87 +/- 4.28 MUg/mL vs
      6.28 +/- 3.61 MUg/mL; P < .001). Levels of DM were significantly higher in
      patients with late-stage EAC than early-stage EAC (10.61 +/- 4.79 MUg/mL vs 8.97
      +/- 3.36 MUg/mL; P = .005). Higher levels of LP were associated with significant
      decrease in risk of EAC (odds ratio [OR], 0.26; 95% confidence interval [CI],
      0.18-0.38). A significant increase in risk of EAC was associated with higher
      levels of BHBA (OR, 4.05; 95% CI, 2.84-5.78) and DM (OR, 7.04; 95% CI, 4.79
      10.34). Levels of all 3 metabolites associated with EAC risk in a dose response
      manner; the level of risk conferred by the metabolites increased jointly with
      smoking status and body mass index. Individuals with high MRS had significant
      (7.76-fold) increase in risk of EAC vs those with low MRS. Smokers with high MRS
      had the greatest risk of EAC (OR, 23.40; 95% CI, 10.95-50.00), compared with
      never smokers with low MRS. CONCLUSIONS: On the basis of a case vs control
      metabolic profile analysis, levels of LP, BHBA, and DM are associated with risk
      of EAC. These markers might be used as risk and prognostic factors for patients
      with EAC.

PMID- 25998792
TI  - A new practical diagnostic test for Creutzfeldt-Jakob disease.

PMID- 25998791
TI  - Thrombolysis for Acute Minor Stroke: Outcome and Barriers to Management. Results
      from the RESUVAL Stroke Network.
AB  - BACKGROUND: We evaluated the management, outcome and haemorrhagic risk in a
      cohort of ischaemic stroke patients with mild symptoms treated with intravenous
      tissue plasminogen activator (tPA) within the first 4.5 h. METHODS: We analysed
      data from a prospective stroke thrombolysis registry. A total of 1,043 patients
      received tPA between 2010 and 2014 in the 5 stroke units of the RESUVAL stroke
      network (Rhone Valley, France). Among them, 170 patients had a National Institute
      of Health Stroke Scale (NIHSS) score <=4 (minor group: MG) before tPA and 873
      patients had a NIHSS score >4. RESULTS: A high rate (77%) of excellent outcome (3
      month-modified Rankin Scale score <=1) was observed in the MG. No symptomatic
      intracerebral haemorrhage occurred and the rate of any haemorrhagic
      transformation was 5%. Fifty-four percent of the MG patients had visible arterial
      occlusion before tPA. Patients of the MG were less likely to be transported by
      Emergency Medical Services and to be directly admitted to the stroke unit or to
      imaging. Median delays from onset to admission, from admission to imaging and
      from onset to tPA were longer in the MG. CONCLUSION: Our data provided evidence
      of safety and suggested potential benefit of thrombolysis in patients with NIHSS
      score <=4. A majority of these patients exhibited arterial occlusion before
      thrombolysis. Most often, patients with mild stroke are not given priority in
      terms of the mode of transport, direct admission to stroke unit and rapid
      imaging, resulting in an increased delay from onset to thrombolysis. Health
      system improvements are needed to provide all suspected stroke victims equal
      access to imaging and treatment on an emergency basis.

PMID- 25998794
TI  - Phrenology, heredity and progress in George Combe's Constitution of Man.
AB  - The Constitution of Man by George Combe (1828) was probably the most influential
      phrenological work of the nineteenth century. It not only offered an exposition
      of the phrenological theory of the mind, but also presented Combe's vision of
      universal human progress through the inheritance of acquired mental attributes.
      In the decades before the publication of Darwin's Origin of Species, the
      Constitution was probably the single most important vehicle for the dissemination
      of naturalistic progressivism in the English-speaking world. Although there is a
      significant literature on the social and cultural context of phrenology, the role
      of heredity in Combe's thought has been less thoroughly explored, although both
      John van Wyhe and Victor L. Hilts have linked Combe's views on heredity with the
      transformist theories of Jean-Baptiste Lamarck. In this paper I examine the
      origin, nature and significance of his ideas and argue that Combe's
      hereditarianism was not directly related to Lamarckian transformism but formed
      part of a wider discourse on heredity in the early nineteenth century. 

PMID- 25998793
TI  - 1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial
      barrier disruption.
AB  - The loss of airway epithelial integrity contributes significantly to asthma
      pathogenesis. Evidence suggests that vitamin D plays an important role in the
      prevention and treatment of asthma. However, its role in airway epithelial
      barrier function remains uncertain. We have previously demonstrated impaired
      epithelial junctions in a model of toluene diisocyanate (TDI)-induced asthma. In
      the present study, we hypothesized that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      may prevent TDI-induced epithelial barrier disruption. Male BALB/c mice were
      dermally sensitized and then challenged with TDI. The mice were then administered
      1,25(OH)2D3 intraperitoneally prior to challenge with TDI. For in vitro
      experiments, 16HBE bronchial epithelial cells were cultured and stimulated with
      TDI-human serum albumin (HSA). The results revealed that the mice treated with
      1,25(OH)2D3 displayed decreased airway hyperresponsiveness (AHR), suppressed
      neutrophil and eosinophil infiltration into the airways, as well as an increased
      E-cadherin and zonula occludens-1 (ZO-1) expression at the cell-cell contact
      sites. In vitro, exposure of the cells to TDI-HSA induced a rapid decline in
      transepithelial electrical resistance (TER) and an increase in cell permeability,
      followed by a decrease in occludin expression and the redistribution of E
      cadherin, accompanied by a significant upregulation in the levels of
      phosphorylated extracellular signal-regulated kinase (ERK)1/2. These effects were
      all partly reversed by treatment with either 1,25(OH)2D3 or an ERK1/2 inhibitor.
      In conclusion, the findings of our study demonstrate that 1,25(OH)2D3 prevents
      TDI-induced epithelial barrier disruption, and that the ERK1/2 pathway may play a
      role in this process.

PMID- 25998795
TI  - The complete mitochondrial genome of Pseudoterranova azarasi and comparative
      analysis with other anisakid nematodes.
AB  - Anisakiasis/anisakidosis caused by anisakid nematodes is an emerging infectious
      disease that can cause a wide range of clinical syndromes and are difficult to
      diagnose and treat in humans. In spite of their significance as pathogens, the
      systematics, genetics, epidemiology and biology of these parasites remain poorly
      understood. In the present study, we sequenced the complete mitochondrial (mt)
      genome of Pseudoterranova azarasi, which is one of the most important zoonotic
      anisakid parasites. The circular mt genome is 13,954 bp in size and encodes of 36
      genes, including 12 protein-coding, 2 ribosomal RNA and 22 transfer RNA genes.
      The mt gene order of P. azarasi is the same as those of Ascaris spp.
      (Ascarididae), Toxocara spp. (Toxocaridae) and Anisakis simplex (Anisakidae), but
      distinct from those of Ascaridia spp. (Ascaridiidae) and Cucullanus robustus
      (Cucullanidae). Phylogenetic analyses based on concatenated amino acid sequences
      of 12 protein-coding genes by Bayesian inference (BI) showed that Pseudoterranova
      were more closely related to Anisakis than they were to Contracaecum with strong
      a posterior probability support. This mt genome provides a novel genetic markers
      for exploring cryptic/sibling species and host affiliations, and should have
      implications for the diagnosis, prevention and control of anisakidosis in humans.

PMID- 25998796
TI  - Application of Cloud Point Extraction for Cadmium in Biological Samples of
      Occupationally Exposed Workers: Relation Between Cadmium Exposure and Renal
      Lesion.
AB  - Cadmium (Cd) level in blood and urine of soldering iron workers (n=49) and 41
      matched healthy controls has been assessed. Cloud point extraction was employed
      for preconcentration of Cd. The Cd ions formed hydrophobic complex with 9,10
      phenanthraquinone monoethyl thiosemicarbazone that was extracted by surfactant
      rich phases in the nonionic surfactant Triton X-114. The surfactant-rich phase
      was diluted with 1 M HNO3 in methanol prior to its analysis by graphite furnace
      atomic absorption spectrometry. The parameters affecting the extraction
      efficiency of the proposed method, such as solution pH, amount of complexing
      agent, surfactant concentration, temperature, and incubation time, were
      optimized. Under the optimum experimental conditions, the detection limit and the
      enrichment factor were 0.04 MUg L(-1) and 61, respectively. Relative standard
      deviation of 10 MUg L(-1) Cd was less than 3.0%. The accuracy of the method was
      examined by analysis of certified reference materials. It was observed that
      soldering iron workers are liable to Cd overload as indicated by higher levels of
      Cd in blood and urine when compared with the controls. This exposure may lead to
      kidney damage indicated by elevation of urinary excretion of both N-acetyl-beta-D
      glucosaminidase and beta2-microglobulin.

PMID- 25998797
TI  - Analysis of Annual Changes in the Concentrations of Selected Macro- and
      Microelements, Thyroxine, and Testosterone in the Serum of Red Deer (Cervus
      elaphus) Stags.
AB  - The aim of the study was to analyze seasonal changes in the concentrations of
      calcium, phosphorus, magnesium, and selenium as well as thyroxine and
      testosterone in adult red deer stags. The highest testosterone concentrations
      (mean 6.29+/-4.36 ng/ml) were observed from the end of August to November,
      confirming an increase in testicular secretory activity during the mating season.
      The changes in thyroxine concentration show circannual rhythms, most likely
      related to changes in the air temperature. The highest mean level of thyroxine
      was observed in spring (55.69+/-10.99 ng/ml). The concentration of selenium also
      reached the highest level during this season (0.107+/-0.027 MUg/ml). In the case
      of the studied macroelements, the concentrations were stable from spring to
      summer but then decreased to the lowest mean values in autumn in both years of
      the experiment (Ca, 61.17+/-10.60; P, 47.08+/-9.59; Mg, 15.96+/-2.39 MUg/ml). The
      dynamics of thyroxine secretion does not seem to affect directly the metabolism
      of calcium, phosphorus, and magnesium. In turn, sexual activity, manifested in
      the increase in secretion of testosterone, may affect changes in the
      concentration of calcium. Additionally, we cannot exclude a connection between
      changes in the concentrations of testosterone and selenium.

PMID- 25998798
TI  - Burden and coping strategies among Jordanian caregivers of patients undergoing
      hemodialysis.
AB  - Recent studies reported hemodialysis patients' sufferings from physical and
      psychosocial issues, but few studies reported family-caregiver burdens. This
      study aims to explore the burdens and coping strategies of caregivers of patients
      receiving hemodialysis. Caregivers of patients undergoing hemodialysis (n = 139)
      at 3 dialysis units were given 3 forms: Caregiver and Patient Characteristics,
      Oberst Caregiving Burden Scale Difficulty Subscale, and Ways of Coping
      Questionnaire. Descriptive statistics, correlational analysis, and multiple
      regression analysis were performed. The Oberst Caregiving Burden Scale was
      significantly related to self-controlling (r = 0.20) and seeking social support
      (r = 0.17). Caregiver burden was positively and significantly correlated with
      self-controlling coping subscale, with t = 1.10, P = 0.05, and beta = 0.25.
      Living with the patient was the only variable that was a significant predictor of
      burden, with t = 2.96, P = 0.00, and beta = 0.331. Living with patients predicted
      caregiver burden, and the burden scale correlated with self-controlling. The
      findings contribute to the evidence on the adverse health effects of caregivers
      of patients receiving hemodialysis. This study suggests that nursing
      interventions should target caregiver knowledge for better coping. 

PMID- 25998799
TI  - Biodegradable hollow silica nanospheres containing gold nanoparticle arrays.
AB  - We introduce biodegradable hollow silica nanocapsules embedding arrays of 3 nm
      gold nanoparticles. The silica shell degrades in full serum in a few hours,
      potentially allowing the clearance of the capsules and their contents by the
      efficient renal pathway, and thereby overcoming accumulation issues typical of
      metal nanoparticles. 

PMID- 25998801
TI  - Thermally Switched Release from a Nanogel-in-Microfiber Device.
AB  - A nanogel-in-microfiber device, whose release can be switched on and off in
      response to a temperature change, is successfully developed. The release
      behaviors are realized through the deswelling and swelling of the nanogels in
      shell layer of fiber by alternatively elevating and lowering the environmental
      temperature. 

PMID- 25998802
TI  - A KCNJ10 mutation previously identified in the Russell group of terriers also
      occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related
      breeds.
AB  - BACKGROUND: Hereditary ataxias with similar phenotypes were reported in the
      Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell
      Terrier. However, segregation analyses showed differing inheritance modes in
      these breeds. Recently, molecular genetic studies on the Russell group of
      terriers found independent mutations in KCNJ10 and CAPN1, each associated with a
      specific clinical subtype of inherited ataxia. The aim of this study was to
      clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs
      of other related breeds harbor either of the same mutations. A sub goal was to
      update the results of KCNJ10 genotyping in Russell group terriers. FINDINGS:
      Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers
      with a similar phenotype were all homozygous for the KCNJ10 mutation. The same
      mutation was also found in a heterozygous state in clinically unaffected
      Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack
      Russell Terriers, Parson Russell Terriers, and Russell Terriers. CONCLUSIONS: A
      KCNJ10 mutation, previously associated with an autosomal recessive
      spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and
      Russell Terriers segregates in at least three more breeds descended from British
      hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox
      Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening
      the likelihood that this genetic defect is indeed the causative mutation for the
      disease known as "hereditary ataxia" in Fox Terriers and "spinocerebellar ataxia
      with myokymia, seizures or both" in the Russell group of terriers.

PMID- 25998800
TI  - Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor
      immune responses in a human MUC1-expressing preclinical ovarian cancer model.
AB  - Monoclonal antibodies that block inhibitory immune checkpoint molecules and
      enhance anti-tumor responses show clinical promise in advanced solid tumors. Most
      of the preliminary evidence on therapeutic efficacy of immune checkpoint blockers
      comes from studies in melanoma, lung and renal cancer. To test the in vivo
      potential of programmed death-ligand 1 (PD-L1) blockade in ovarian cancer, we
      recently generated a new transplantable tumor model using human mucin 1 (MUC1)
      expressing 2F8 cells. The MUC1 transgenic (MUC1.Tg) mice develop large number of
      intraperitoneal (IP) tumors following IP injection of 8 * 10(5) syngeneic 2F8
      cells. The tumors are aggressive and display little T cell infiltration. Anti-PD
      L1 antibody was administered IP every 2 weeks (200 MUg/dose) for a total of three
      doses. Treatment was started 21 days post-tumor challenge, a time point which
      corresponds to late tumor stage. The anti-PD-L1 treatment led to substantial T
      cell infiltration within the tumor and significantly increased survival (p =
      0.001) compared to isotype control-treated mice. When the same therapy was
      administered to wild-type mice challenged with 2F8 tumors, no survival benefit
      was observed, despite the presence of high titer anti-MUC1 antibodies. However,
      earlier treatment (day 11) and higher frequency of IP injections restored the T
      cell responses and led to prolonged survival. Splenocyte profiling via Nanostring
      using probes for 511 immune genes revealed a treatment-induced immune gene
      signature consistent with increased T cell-mediated immunity. These findings
      strongly support further preclinical and clinical strategies exploring PD-L1
      blockade in ovarian cancer.

PMID- 25998803
TI  - Anatomic features of interest in women at risk of cardiac exposure from whole
      breast radiotherapy.
AB  - BACKGROUND AND PURPOSE: Left-sided breast radiotherapy (RT) can result in cardiac
      exposure. This study aims to identify predictive anatomic features in women
      requiring breath-hold (RT(BH)) for cardiac sparing during adjuvant whole breast
      RT. MATERIAL AND METHODS: We retrospectively reviewed free-breathing (FB) CT
      scans of 80 women previously treated with left-sided breast RT. Unfavourable
      cardiac anatomy was defined as the number of consecutive axial CT slices (2 mm)
      in which the anterior chest wall contacted the heart (Contact(Heart)) or left
      ventricle (Contact(LV)). The sternal angle and Haller Index (HI) were used to
      measure chest concavity. Position and volume of post-operative cavity was also
      quantified. RESULTS: Heart mean dose (D(mean)) was strongly correlated with
      Contact(LV) (r=0.625, p<0.001) and Contact(Heart) (r=0.524, p<0.001) but not
      significantly correlated with tumor size, cavity volume, heart volume, cavity
      distance to chest wall, sternal angle, or HI. ROC analysis of Contact(Heart) was
      most predictive of the need for breath-hold (RT(BH)) technique [Area Under
      Curve=0.815 (SE: 0.048; 95% CI: 0.721-0.91)] and ?25 Contact(Heart) CT slices
      predicted for heart D(mean) ?1.7 Gy (68% sensitivity and 82% specificity).
      CONCLUSION: Contact(Heart) on FB CT of ?25 axial slices (2 mm), ?50 mm of para
      sagittal heart contact, was predictive of higher heart D(mean) and suggest a
      potential need for RT(BH).

PMID- 25998804
TI  - Short-term pretreatment DCE-MRI in prediction of outcome in locally advanced
      cervical cancer.
AB  - BACKGROUND AND PURPOSE: Several investigators have indicated that dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to
      provide biomarkers for personalized treatment of cervical carcinoma. However,
      some clinical studies have suggested that treatment failure is associated with
      low tumor signal enhancement, whereas others have reported associations between
      high signal enhancement and poor outcome. The purpose of this investigation was
      to clear up these conflicting reports and to provide a method for identifying
      biomarkers that easily can be implemented in routine DCE-MRI diagnostics.
      METHODS: The study involved 85 patients (FIGO stage IB through IVA) treated with
      concurrent chemoradiotherapy. Low-enhancing tumor volume (LETV) and low-enhancing
      tumor fraction (LETF), defined as the volume and fractional volume of low
      enhancing voxels, respectively, were calculated from signal intensities recorded
      within 1 min after contrast administration by using two methods reported to give
      conflicting conclusions. RESULTS: Multivariate analysis involving tumor volume,
      lymph node status, FIGO stage, and LETV or LETF revealed that LETV and LETF
      provided independent prognostic information on treatment outcome, independent of
      the method of calculation. CONCLUSION: Low signal enhancement is associated with
      poor prognosis in cervical carcinoma, and biomarkers predicting poor outcome can
      be provided by short-term DCE-MRI without advanced image analysis.

PMID- 25998805
TI  - Tumor volume threshold for achieving improved conformity in VMAT and Gamma Knife
      stereotactic radiosurgery for vestibular schwannoma.
AB  - BACKGROUND AND PURPOSE: Recent advances in multileaf collimator field shaping
      technology and inverse planning software have resulted in highly conformal LINAC
      based stereotactic radiosurgery (SRS) plans with minimal dose to critical
      structures. This modeling study compares Gamma Knife (GK) and LINAC SRS for
      vestibular schwannoma (VS). MATERIALS AND METHODS: 76 treatment plans from
      nineteen patients with VS were planned using GK forward planning and volumetric
      arc therapy (VMAT) inverse planning software. VMAT plans were generated with 1
      coplanar, 3 and 5 non-coplanar arcs. Dose to normal structures and beam-on time
      (dose rate 600MU/min) were compared using Kruskal-Wallis and Dunn's post hoc
      test. RESULTS: Median tumor volume was 1.2cm(3) (range 0.1-4.8cm(3)). A
      peripheral tumor dose of 12Gy was prescribed. Tumor coverage was >99.8%. VMAT
      plans had lower target D2% and mean dose, as well as decreased beam-on time,
      compared to GK plans (p<0.0001). Paddick conformity index in VMAT 5 arc plans was
      superior to that of GK plans for targets >0.5cm(3) (p=0.002). Similar dose to
      cochlea, normal brain tissue and brainstem was observed. CONCLUSION: VMAT should
      be considered as a safe, alternative modality to GK for VS SRS treatment,
      especially for tumors larger than 0.5cm(3).

PMID- 25998807
TI  - Facilitating quality control for spectra assignments of small organic molecules:
      nmrshiftdb2--a free in-house NMR database with integrated LIMS for academic
      service laboratories.
AB  - nmrshiftdb2 supports with its laboratory information management system the
      integration of an electronic lab administration and management into academic NMR
      facilities. Also, it offers the setup of a local database, while full access to
      nmrshiftdb2's World Wide Web database is granted. This freely available system
      allows on the one hand the submission of orders for measurement, transfers
      recorded data automatically or manually, and enables download of spectra via web
      interface, as well as the integrated access to prediction, search, and assignment
      tools of the NMR database for lab users. On the other hand, for the staff and lab
      administration, flow of all orders can be supervised; administrative tools also
      include user and hardware management, a statistic functionality for accounting
      purposes, and a 'QuickCheck' function for assignment control, to facilitate
      quality control of assignments submitted to the (local) database. Laboratory
      information management system and database are based on a web interface as front
      end and are therefore independent of the operating system in use.

PMID- 25998806
TI  - A multi-centre analysis of treatment procedures and error components in dynamic
      tumour tracking radiotherapy.
AB  - PURPOSE: This study aimed to compare procedures for dynamic tumour tracking (DTT)
      using a gimbal-mounted linac between centres in Japan (KU-IBRI) and Belgium
      (UZB), to quantify tracking error (TE), and to estimate tumour-fiducial
      uncertainties and PTV margins. METHODS: Twenty-two patients were evaluated. TE
      was divided into components originating from the patient, fraction, segment, and
      residuals. RESULTS: KU-IBRI applied DTT to lung cancer, while UZB treated both
      the lung and liver. Patients from UZB were younger and had a higher body mass
      index. DTT procedures differed in the use of body fixation, correction for set-up
      error, type of fiducial markers, and goodness of fit of correlation model. TE was
      larger at UZB in the intra-fraction components, whereas the tumour-fiducial
      uncertainties were estimated to be larger at KU-IBRI. These results ultimately
      led to similar PTV margins at both centres (2.1, 4.2, and 2.6 mm for KU-IBRI;
      2.4, 3.6, and 2.0 mm for UZB in LR, AP, and SI, respectively, for 99% coverage of
      patients). CONCLUSION: Several differences in procedures and patient
      characteristics were observed that affected TE and tumour-fiducial uncertainties.
      This analysis confirmed similar accuracy in DTT delivery and adequate PTV margins
      in the different centres based on their local specific workflows.

PMID- 25998808
TI  - Inactivation of avirulent Yersinia pestis on food and food contact surfaces by
      ultraviolet light and freezing.
AB  - Yersinia pestis, the causative agent of plague, can occasionally be contracted as
      a naso-pharyngeal or gastrointestinal illness through consumption of contaminated
      meat. In this study, the use of 254 nm ultraviolet light (UV-C) to inactivate a
      multi-isolate cocktail of avirulent Y. pestis on food and food contact surfaces
      was investigated. When a commercial UV-C conveyor was used (5 mW/cm(2)/s) 0.5
      J/cm(2) inactivated >7 log of the Y. pestis cocktail on agar plates. At 0.5
      J/cm(2), UV-C inactivated ca. 4 log of Y. pestis in beef, chicken, and catfish,
      exudates inoculated onto high density polypropylene or polyethylene, and
      stainless steel coupons, and >6 log was eliminated at 1 J/cm(2). Approximately 1
      log was inactivated on chicken breast, beef steak, and catfish fillet surfaces at
      a UV-C dose of 1 J/cm(2). UV-C treatment prior to freezing of the foods did not
      increase the inactivation of Y. pestis over freezing alone. These results
      indicate that routine use of UV-C during food processing would provide workers
      and consumers some protection against Y. pestis. 

PMID- 25998809
TI  - Sublethal injury and virulence changes in Listeria monocytogenes and Listeria
      innocua treated with antimicrobials carvacrol and citral.
AB  - The aim of this study was to evaluate the effect of two antimicrobial substances,
      carvacrol and citral, on Listeria monocytogenes and Listeria innocua cells, as
      well as possible virulence changes in injured cells, using Caenorhabditis elegans
      as a model test. The results indicated that the percentage of sublethal damage
      was higher in L. monocytogenes than in L. innocua. The results of the study
      carried out by using C. elegans indicated that C. elegans fed in a lawn of L.
      monocytogenes previously treated with carvacrol showed a loss in life span (p <=
      0.05) as compared with L. monocytogenes treated with citral, Escherichia coli
      OP50 as a negative control, and treated and untreated L. innocua. Egg laying was
      also affected: worms fed in a lawn of treated and untreated L. monocytogenes laid
      fewer eggs than those fed in a lawn of treated and untreated L. innocua or fed
      with OP50 as a negative control. Worms fed in a lawn of treated and untreated L.
      innocua also laid fewer eggs than those fed with OP50 as a negative control. A
      phenotype named bag of worms and an undescribed new one, "vulva inflammation",
      were also observed. 

PMID- 25998810
TI  - Microbial biogeography of the transnational fermented milk matsoni.
AB  - The fermented milk matsoni is a traditional, national food product of both
      Georgia and Armenia. Little is known about the effects of biogeography and milk
      type on the microbial biodiversity of matsoni or the fungal composition of
      matsoni fermentations. High-throughput marker-gene sequencing was used to survey
      the bacterial and fungal communities of matsoni from different milk types and
      regions throughout Armenia and Georgia. Results demonstrate that both production
      region and milk type influence matsoni microbiota, suggesting that the
      traditional production methods preserve the transfer of unique regional
      microbiota from batch to batch. Bacterial profiles were dominated by
      Lactobacillus and Streptococcus species. Yeast profiles varied dramatically, with
      Kluyveromyces marxianus, Candida famata, Saccharomyces cerevisiae, Lodderomyces
      elongisporus, and Kluyveromyces lactis being the most important species
      distinguishing production regions and milk types. This survey will enable more
      detailed capture and characterization of specific microbiota detected within
      these fermentations. 

PMID- 25998811
TI  - Virulence characterization of non-O157 Shiga toxin-producing Escherichia coli
      isolates from food, humans and animals.
AB  - A total of 359 non-O157 STEC isolates from food, humans and animals were examined
      for serotypes, Shiga toxin subtypes and intimin subtypes. Isolates solely
      harboring stx2 from the three sources were selected for Vero cell cytotoxicity
      test. stx subtypes in eae negative isolates were more diverse than in eae
      positive isolates primarily carrying stx2a. Four eae subtypes
      (eaebeta,eaeepsilon1,eaegamma1 and eaegamma2/theta) were observed and correlated
      with serotypes and flagella. Food isolates showed more diverse serotypes,
      virulence factors and cell cytotoxicities than human isolates. Some isolates from
      produce belonged to serotypes that have been implicated in human diseases,
      carried stx2a or/and stx2dact and exhibited high cell cytotoxicity similar to
      human isolates. This indicates that foods can be contaminated with potentially
      pathogenic STEC isolates that may cause human diseases. Given the increased
      produce consumption and growing burden of foodborne outbreaks due to produce,
      produce safety should be given great importance. 

PMID- 25998812
TI  - Development of a real-time PCR assay for Penicillium expansum quantification and
      patulin estimation in apples.
AB  - Due to the occurrence and spread of the fungal contaminants in food and the
      difficulties to remove their resulting mycotoxins, rapid and accurate methods are
      needed for early detection of these mycotoxigenic fungi. The polymerase chain
      reaction and the real time PCR have been widely used for this purpose. Apples are
      suitable substrates for fungal colonization mostly caused by Penicillium
      expansum, which produces the mycotoxin patulin during fruit infection. This study
      describes the development of a real-time PCR assay incorporating an internal
      amplification control (IAC) to specifically detect and quantify P. expansum. A
      specific primer pair was designed from the patF gene, involved in patulin
      biosynthesis. The selected primer set showed a high specificity for P. expansum
      and was successfully employed in a standardized real-time PCR for the direct
      quantification of this fungus in apples. Using the developed system, twenty eight
      apples were analyzed for their DNA content. Apples were also analyzed for patulin
      content by HPLC. Interestingly, a positive correlation (R(2) = 0.701) was found
      between P. expansum DNA content and patulin concentration. This work offers an
      alternative to conventional methods of patulin quantification and mycological
      detection of P. expansum and could be very useful for the screening of patulin in
      fruits through the application of industrial quality control. 

PMID- 25998813
TI  - A proposed harmonized LPS molecular-subtyping scheme for Cronobacter species.
AB  - Cronobacter are opportunistic pathogens, which cause infections in all age
      groups. To aid the characterization of Cronobacter in foods and environments a
      harmonized LPS identification scheme for molecular serotyping is needed. To this
      end, we studied 409 Cronobacter isolates representing the seven Cronobacter
      species using two previously reported molecular serotyping schemes, described
      here as Mullane-Jarvis (M-J) and Sun schemes. PCR analysis revealed many
      overlapping results that were obtained when independently applying the two
      serotyping schemes. There were complete agreements between the two PCR schemes
      for Cronobacter sakazakii (Csak) O:1, Csak O:3, and Csak O:7 serotypes. However,
      only thirty-five of 41 Csak O:4 strains, identified using the M-J scheme, were
      PCR-positive with the Sun scheme primers. Also the Sun scheme Csak O:5 primers
      failed to identify this serotype in any of the C. sakazakii strains tested, but
      did recognize seven Cronobacter turicensis strains, which were identified as Ctur
      O:3 using the M-J scheme. Similarly, the Sun scheme Csak O:6 primers recognized
      30 Cronobacter malonaticus O:2 strains identified with the M-J scheme, but failed
      to identify this serotype in any C. sakazakii strain investigated. In this
      report, these findings are summarized and a harmonized molecular-serotyping
      scheme is proposed which is predicated on the correct identification of
      Cronobacter species, prior to serotype determination. In summary, fourteen
      serotypes were identified using the combined protocol, which consists of Csak O:1
      O:4, and Csak O:7; Cmal O:1-O:2; Cdub O:1-O:2, Cmuy O:1-O:2, Cuni O:1, as well as
      Ctur O:1 and Ctur O:3. 

PMID- 25998814
TI  - Microbiological spoilage and volatiles production of gutted European sea bass
      stored under air and commercial modified atmosphere package at 2  degrees C.
AB  - Microbiological, sensory, TVB-N and TMA-N changes and Volatile Organic Compounds
      (VOCs) detection using the SPME/GC-MS technique, were performed to evaluate
      potential chemical spoilage indices (CSI) of gutted sea bass (Dicentrarchus
      labrax) stored at 2  degrees C under air and in modified atmosphere packaging
      (MAP CO2: 60%, O2: 10%, N2: 30%). Shelf-life, determined by sensory evaluation,
      of gutted sea bass stored at 2  degrees C under air and MAP was 9 and 13 d
      respectively. Pseudomonas and H2S producing bacteria were among the dominant
      spoilage microorganisms under both storage conditions, while Lactic Acid Bacteria
      (LAB) and Brochothrix thermosphacta were co-dominant with Pseudomonas and H2S
      producing bacteria under MAP. The traditional CSIs such as TVB-N and TMA-N were
      increased substantially only at the late stages of storage or after rejection of
      the products, making them unsuitable for freshness/spoilage monitoring throughout
      storage. A substantial number of VOCs attributed to microbiological action or
      chemical activity, were detected including alcohols, aldehydes, ketones, organic
      acids and esters. The level of microbial origin VOCs such as ethanol, 2-ethyl-1
      hexanol, 3-methyl-1-butanol, 2-methyl-1-butanol, 3-methylbutanal, 2-methylbutanal
      and some ethyl esters increased during storage, suggesting their potential as
      CSIs. 

PMID- 25998815
TI  - Applying meta-pathway analyses through metagenomics to identify the functional
      properties of the major bacterial communities of a single spontaneous cocoa bean
      fermentation process sample.
AB  - A high-resolution functional metagenomic analysis of a representative single
      sample of a Brazilian spontaneous cocoa bean fermentation process was carried out
      to gain insight into its bacterial community functioning. By reconstruction of
      microbial meta-pathways based on metagenomic data, the current knowledge about
      the metabolic capabilities of bacterial members involved in the cocoa bean
      fermentation ecosystem was extended. Functional meta-pathway analysis revealed
      the distribution of the metabolic pathways between the bacterial members
      involved. The metabolic capabilities of the lactic acid bacteria present were
      most associated with the heterolactic fermentation and citrate assimilation
      pathways. The role of Enterobacteriaceae in the conversion of substrates was
      shown through the use of the mixed-acid fermentation and methylglyoxal
      detoxification pathways. Furthermore, several other potential functional roles
      for Enterobacteriaceae were indicated, such as pectinolysis and citrate
      assimilation. Concerning acetic acid bacteria, metabolic pathways were partially
      reconstructed, in particular those related to responses toward stress, explaining
      their metabolic activities during cocoa bean fermentation processes. Further, the
      in-depth metagenomic analysis unveiled functionalities involved in bacterial
      competitiveness, such as the occurrence of CRISPRs and potential bacteriocin
      production. Finally, comparative analysis of the metagenomic data with bacterial
      genomes of cocoa bean fermentation isolates revealed the applicability of the
      selected strains as functional starter cultures. 

PMID- 25998816
TI  - Batch-to-batch uniformity of bacterial community succession and flavor formation
      in the fermentation of Zhenjiang aromatic vinegar.
AB  - Solid-state fermentation of traditional Chinese vinegar is a mixed-culture
      refreshment process that proceeds for many centuries without spoilage. Here, we
      investigated bacterial community succession and flavor formation in three batches
      of Zhenjiang aromatic vinegar using pyrosequencing and metabolomics approaches.
      Temporal patterns of bacterial succession in the Pei (solid-state vinegar
      culture) showed no significant difference (P > 0.05) among three batches of
      fermentation. In all the batches investigated, the average number of community
      operational taxonomic units (OTUs) decreased dramatically from 119 +/- 11 on day
      1 to 48 +/- 16 on day 3, and then maintained in the range of 61 +/- 9 from day 5
      to the end of fermentation. We confirmed that, within a batch of fermentation
      process, the patterns of bacterial diversity between the starter (took from the
      last batch of vinegar culture on day 7) and the Pei on day 7 were similar (90%).
      The relative abundance dynamics of two dominant members, Lactobacillus and
      Acetobacter, showed high correlation (coefficient as 0.90 and 0.98 respectively)
      among different batches. Furthermore, statistical analysis revealed dynamics of
      16 main flavor metabolites were stable among different batches. The findings
      validate the batch-to-batch uniformity of bacterial community succession and
      flavor formation accounts for the quality of Zhenjiang aromatic vinegar. Based on
      our understanding, this is the first study helps to explain the rationality of
      age-old artistry from a scientific perspective. 

PMID- 25998817
TI  - Diversity of yeast strains of the genus Hanseniaspora in the winery environment:
      What is their involvement in grape must fermentation?
AB  - Isolated yeast populations of Chardonnay grape must during spontaneous
      fermentation were compared to those isolated on grape berries and in a winery
      environment before the arrival of the harvest (air, floor, winery equipment) and
      in the air through time. Two genera of yeast, Hanseniaspora and Saccharomyces,
      were isolated in grape must and in the winery environment before the arrival of
      the harvest but not on grape berries. The genus Hanseniaspora represented 27% of
      isolates in the must and 35% of isolates in the winery environment. The isolates
      of these two species were discriminated at the strain level by Fourier transform
      infrared spectroscopy. The diversity of these strains observed in the winery
      environment (26 strains) and in must (12 strains) was considerable. 58% of the
      yeasts of the genus Hanseniaspora isolated in the must corresponded to strains
      present in the winery before the arrival of the harvest. Although the proportion
      and number of strains of the genus Hanseniaspora decreased during fermentation,
      some strains, all from the winery environment, subsisted up to 5% ethanol
      content. This is the first time that the implantation in grape must of
      populations present in the winery environment has been demonstrated for a non
      Saccharomyces genus. 

PMID- 25998818
TI  - Tetragenococcus koreensis is part of the microbiota in a traditional Italian raw
      fermented sausage.
AB  - This study reports the isolation of Tetragenococcus koreensis, a bacterial
      species currently represented only by the type strain isolated from kimchi, from
      a raw fermented and ripened Italian sausage, Ventricina Vastese, all over the
      ripening period of five months. Rep-PCR genotyping showed that different T.
      koreensis strains, identified by sequencing of the 16S rRNA gene, were present in
      the same production batch. Tests on representative isolates showed intra-species
      physiological variability and the possession of phenotypic traits relevant for
      the production of fermented sausages, i.e. ability to grow at high salt
      concentrations, to induce some changes in the peptide profile of the culture
      medium and inability to produce histamine and tyramine, confirmed by the absence
      of the respective decarboxylase genes. Therefore the opportunity to further
      investigate the suitability of T. koreensis as a starter for fermented meat
      products was suggested. 

PMID- 25998819
TI  - Location and stoichiometry of the protease CspB and the cortex-lytic enzyme SleC
      in Clostridium perfringens spores.
AB  - The protease CspB and the cortex-lytic enzyme SleC are essential for peptoglycan
      cortex hydrolysis during germination of spores of the Clostridium perfringens
      food poisoning isolate SM101. In this study, Western blot analyses were used to
      demonstrate that CspB and SleC are present exclusively in the C. perfringens
      SM101 spore coat layer fraction and absent in the lysate from decoated spores and
      from the purified inner spore membrane. These results indicate why decoating
      treatments greatly reduce both germination and apparent viability of C.
      perfringens spores in the absence of an exogenous lytic enzyme. In addition,
      quantitative Western blot analyses showed that there are approximately 2000 and
      130,000 molecules of CspB and pro-SleC, respectively, per C. perfringens SM101
      spore, consistent with CspB's role in acting catalytically on pro-SleC to convert
      this zymogen to the active enzyme. 

PMID- 25998820
TI  - Inactivation dynamics of Salmonella enterica, Listeria monocytogenes, and
      Escherichia coli O157:H7 in wash water during simulated chlorine depletion and
      replenishment processes.
AB  - Maintaining effective sanitizer concentration is of critical importance for
      preventing pathogen survival and transference during fresh-cut produce wash
      operation and for ensuring the safety of finished products. However, maintaining
      an adequate level of sanitizer in wash water can be challenging for processors
      due to the large organic load in the wash system. In this study, we investigated
      how the survival of human pathogens was affected by the dynamic changes in water
      quality during chlorine depletion and replenishment in simulated produce washing
      operations. Lettuce extract was added incrementally into water containing pre-set
      levels of free chlorine to simulate the chlorine depletion process, and sodium
      hypochlorite was added incrementally into water containing pre-set levels of
      lettuce extract to simulate chlorine replenishment. Key water quality parameters
      were closely monitored and the bactericidal activity of the wash water was
      evaluated using three-strain cocktails of Escherichia coli O157:H7, Salmonella
      enterica, and Listeria monocytogenes. In both chlorine depletion and
      replenishment processes, no pathogen survival was observed when wash water free
      chlorine level was maintained above 3.66 mg/L, irrespective of the initial free
      chlorine levels (10, 50, 100 and 200 mg/L) or organic loading (chemical oxidation
      demand levels of 0, 532, 1013 and 1705 mg/L). At this free chlorine
      concentration, the measured ORP was 843 mV and pH was 5.12 for the chlorine
      depletion process; the measured ORP was 714 mV and pH was 6.97 for the chlorine
      replenishment process. This study provides quantitative data needed by the fresh
      cut produce industry and the regulatory agencies to establish critical
      operational control parameters to prevent pathogen survival and cross
      contamination during fresh produce washing. 

PMID- 25998821
TI  - Campylobacter jejuni contamination of broiler carcasses: Population dynamics and
      genetic profiles at slaughterhouse level.
AB  - Six slaughter batches deriving from six typical industrial broiler flocks were
      examined for the presence, quantity and genetic characteristics of contaminating
      Campylobacter jejuni (C. jejuni) during various stages of slaughtering and
      carcass processing. To assess the contamination dynamics of the carcasses, the
      analyses were always conducted on neck-skin samples from the same pre-selected
      and carefully marked carcasses in each batch. The skin samples were taken
      sequentially at three successive slaughter-line locations in the evisceration
      room, after three-day refrigeration and after three-day freezing procedure.
      Caecal samples from the same animals were also tested, as well as samples from
      the slaughterhouse environment before and after slaughtering. The samples were
      analysed by the ISO10272 isolation method; campylobacters from neck-skin samples
      were also quantified. Isolates were species-identified and genotyped by pulsed
      field gel electrophoresis (PFGE). On average, the highest C. jejuni skin
      contamination was detected at the first sampling point (post-plucking),
      suggesting that the majority of Campylobacter contamination actually occurs
      before the entrance to the eviscerating room, probably during the preceding
      plucking stage. In two out of five positive batches, an additional increase in
      contamination was recorded after the evisceration step. An evident trend of
      increasing contamination level was detected when successive batches were compared
      at each of two initial sampling sites in the evisceration room, indicating an
      accumulation of contaminating C. jejuni at some point before the evisceration
      room. Three-day refrigeration and three-day freezing caused a 4.5- and 142-fold
      drop in mean C. jejuni CFU counts, respectively. All pre-slaughtering samples
      from the slaughterhouse environment were negative and all post-slaughtering
      samples, except water from the scalding tank, were positive. Pulsotypes were
      limited: altogether five different types were detected, typically one type per
      batch. The PFGE results from the slaughterhouse environment isolates indicate
      that cross-contamination is possible (multiple pulsotypes detected in e.g.
      eviscerating machine). Nevertheless, this was not confirmed in carcasses:
      analyses of neck-skin isolates suggest that carcasses are contaminated by their
      own caecal/farm/flock pulsotype. 

PMID- 25998822
TI  - Control of spoiler Pseudomonas spp. on fresh cut vegetables by neutral
      electrolyzed water.
AB  - In the present study, we evaluated the antimicrobial activity of neutral
      electrolyzed water (NEW) against 14 strains of spoilage Pseudomonas of fresh cut
      vegetables under cold storage. The NEW, produced from solutions of potassium and
      sodium chloride, and sodium bicarbonate developed up to 4000 mg/L of free
      chlorine, depending on the salt and relative concentration used. The
      antimicrobial effect of the NEW was evaluated against different bacterial strains
      at 10(5) cells/ml, with different combinations of free chlorine
      concentration/contact time; all concentrations above 100 mg/L, regardless of the
      salt used, were found to be bactericidal already after 2 min. When catalogna
      chicory and lettuce leaves were dipped for 5 min in diluted NEW, microbial loads
      of mesophilic bacteria and Enterobacteriaceae were reduced on average of 1.7 log
      cfu/g. In addition, when lettuce leaves were dipped in a cellular suspension of
      the spoiler Pseudomonas chicorii I3C strain, diluted NEW was able to reduce
      Pseudomonas population of about 1.0 log cfu/g. Thanks to its high antimicrobial
      activity against spoilage microorganisms, and low cost of operation, the
      application of cycles of electrolysis to the washing water looks as an effective
      tool in controlling fresh cut vegetable microbial spoilage contamination
      occurring during washing steps. 

PMID- 25998823
TI  - Probiotic features of Lactobacillus strains isolated from Ragusano and Pecorino
      Siciliano cheeses.
AB  - In the present study 177 Lactobacillus spp. strains, isolated from Ragusano and
      Pecorino Siciliano cheeses, were in vitro screened for probiotic traits, and
      their characteristics were compared to those of Lactobacillus rhamnosus GG,
      commercial strain. Based on acidic and bile salt resistance, thirteen
      Lactobacillus strains were selected. The multiplex-PCR application revealed that
      nine strains belonged to L. rhamnosus species and four to Lactobacillus paracasei
      species. All selected strains were further investigated for transit tolerance in
      simulated upper gastrointestinal tract (GI), for adhesion capacity to human
      intestinal cell lines, for hydrophobicity, for co-aggregation and auto
      aggregation and for antimicrobial activities. Moreover, antibiotic resistance,
      hemolytic and bile salt hydrolase activities were investigated for safety
      assessment. Viable counts after simulated gastric and duodenal transit revealed
      that overall the selected lactobacilli tolerated better pancreatic juice and bile
      salts than acidic juice. In particular, three L. rhamnosus strains (FS10, FS2,
      and PS11) and one L. paracasei strain (PM8) increased their cell density after
      the simulated GI transit. The same strains showed also high percentage of auto
      aggregation and co-aggregation with Escherichia coli. All strains were effective
      against both Staphylococcus aureus and E. coli and variability was achieved
      versus Listeria monocytogenes and Enterococcus faecalis used as pathogenic
      indicator strains. Different behavior was revealed by strains for adhesion
      ability and hydrophobicity, which are not always linked each other and are
      strongly strain-dependent. From the safety point of view, no isolate showed
      hemolytic and bile salt hydrolase activities, except one, and most of the strains
      were sensitive to a broad range of clinical antibiotics. This work showed that
      the L. rhamnosus FS10 and the L. paracasei PM8 are good promising probiotic
      candidates for further in vivo investigations. 

PMID- 25998824
TI  - Control of human norovirus surrogates in fresh foods by gaseous ozone and a
      proposed mechanism of inactivation.
AB  - Fresh produce is a major concern for transmission of foodborne enteric viruses as
      it is normally consumed with no heat treatments and minimal other processing to
      ensure safety. Commonly used sanitizers are ineffective at removing foodborne
      viruses from fresh produce. Thus the use of gaseous ozone for viral inactivation
      was investigated. Ozone has great potential for improved food safety because of
      four benefits: It is a potent sanitizer, it is effective against a wide range of
      microorganisms, it is permitted for food use as regulated by the U.S. FDA and
      several other nations, and it spontaneously decomposes to oxygen leaving no
      residue. This study determined the effectiveness of gaseous ozone for the
      sanitization of two norovirus surrogates (MNV-1 and TV) from both liquid media
      and popular fresh foods where viral contamination is common-lettuce and
      strawberries. Foods were treated with gaseous ozone at 6% wt/wt ozone in oxygen
      for 0, 10, 20, 30, and 40 min, and surviving viruses were quantified by viral
      plaque assay. Our results showed that gaseous ozone inactivated norovirus in both
      liquid media and fresh produce in a dose-dependent manner. These results are
      promising because ozone treatment significantly reduced two important norovirus
      surrogates in both liquid and food matrices. Viruses are generally more resistant
      to sanitation treatments than bacteria, thus gaseous ozone is an effective means
      to improve fresh produce safety. 

PMID- 25998825
TI  - An innovative method to produce green table olives based on "pied de cuve"
      technology.
AB  - The technology of "pied de cuve" (PdC) is applied in food process only to produce
      wines with an enriched community of pro-technological yeasts. PdC promotes the
      growth of the desirable microbial strains in a small volume of grape must acting
      as a starter inoculums for higher volumes. The aim of the present work was to
      investigate the use of partially fermented brines, a technology known as PdC,
      developed with lactic acid bacteria (LAB) on the microbiological, chemical and
      sensory characteristics of green fermented table olives during two consecutive
      campaigns. The experimental plan included two trials based on different PdCs:
      trial A, PdC obtained with Lactobacillus pentosus OM13; trial B, PdC obtained
      through a spontaneous fermentation. Two control additional trials without PdC
      were included for comparison: trial C, spontaneous fermentation; trial D, direct
      inoculation of L. pentosus OM13. The use of PdCs favoured the rapid increase of
      LAB concentrations in both trials A and B. These trials showed levels of LAB
      higher than trial C and almost superimposable to that of trial D. Trial B was
      characterized by a certain diversity of L. pentosus strains and some of them
      dominated the manufacturing process. These results indicated PdC as a valuable
      method to favour the growth of autochthonous L. pentosus strains. Hierarchical
      cluster analysis (HCA) and principal component analysis (PCA) visibly
      discriminated olive processes fermented with the two experimental PdCs.
      Interestingly, on the basis of microbial and pH variables, both approaches showed
      that the olives produced with PdC technology are closely related to those of
      trial D, with the advantages of reducing the amount of starter to inoculate
      (trial A) and a higher LAB biodiversity (trial B). Volatile organic compound
      (VOC) composition and sensory analysis showed trials A and B different from the
      trials with no PdC added, in both years. Furthermore, the trial B showed the
      highest scores of green olive aroma and taste complexity. Spoilage microorganisms
      were estimated at very low levels in all trials. Undesired off-odours and off
      flavours were not revealed at the end of the process. 

PMID- 25998826
TI  - Association of TNFSF15 polymorphisms in Korean children with Crohn's disease.
AB  - BACKGROUND: Genome-wide association studies have identified tumor necrosis factor
      superfamily member 15 (TNFSF15) as a Crohn's disease (CD)-related gene. The aim
      of this study was to evaluate the association between five TNFSF15 polymorphisms
      and CD in Korean children and analyze their genotypes in relation to phenotype.
      METHODS: Five single-nucleotide polymorphisms of TNFSF15 (rs3810936, rs6478108,
      rs6478109, rs7848647, rs7865494) were genotyped in 108 CD patients and in 599
      healthy controls. Risk allele, genotype, and haplotype were analyzed in CD
      patients and controls, and genotype-phenotype relationships were studied.
      RESULTS: There were significant associations of rs3810936, rs6478108, rs6478109,
      rs7848647 with CD in Korean pediatric patients (P = 6.5*10(-8), P = 1.3*10(-8), P
      = 3.7*10(-8), P = 2.9*10(-8), respectively). The adjusted OR (aOR) for the
      homozygous risk allele genotype was significantly higher than that for the
      homozygous genotype for the opposite allele: rs3810936, aOR, 5.36 (95%CI: 2.61
      10.98, P = 4.6*10(-6)); rs6478108, aOR, 6.62 (95%CI: 3.03-14.46, P = 2.2*10(-6));
      rs6478109, aOR, 6.24 (95%CI: 2.85-13.66, P = 4.6*10(-6)); rs7848647, aOR, 6.32
      (95%CI: 2.89-13.81, P = 3.8*10(-6)). The risk allele of rs3810936 was associated
      with later symptom onset, later diagnosis, and the presence of perianal lesion (P
      = 0.013, P = 0.016 and P = 0.029). CONCLUSION: There was a significant
      association of TNFSF15 with pediatric CD in Korean patients.

PMID- 25998828
TI  - Lens-based fluorescence nanoscopy.
AB  - The majority of studies of the living cell rely on capturing images using
      fluorescence microscopy. Unfortunately, for centuries, diffraction of light was
      limiting the spatial resolution in the optical microscope: structural and
      molecular details much finer than about half the wavelength of visible light
      (~200 nm) could not be visualized, imposing significant limitations on this
      otherwise so promising method. The surpassing of this resolution limit in far
      field microscopy is currently one of the most momentous developments for studying
      the living cell, as the move from microscopy to super-resolution microscopy or
      'nanoscopy' offers opportunities to study problems in biophysical and biomedical
      research at a new level of detail. This review describes the principles and
      modalities of present fluorescence nanoscopes, as well as their potential for
      biophysical and cellular experiments. All the existing nanoscopy variants
      separate neighboring features by transiently preparing their fluorescent
      molecules in states of different emission characteristics in order to make the
      features discernible. Usually these are fluorescent 'on' and 'off' states causing
      the adjacent molecules to emit sequentially in time. Each of the variants can in
      principle reach molecular spatial resolution and has its own advantages and
      disadvantages. Some require specific transitions and states that can be found
      only in certain fluorophore subfamilies, such as photoswitchable fluorophores,
      while other variants can be realized with standard fluorescent labels. Similar to
      conventional far-field microscopy, nanoscopy can be utilized for dynamical, multi
      color and three-dimensional imaging of fixed and live cells, tissues or
      organisms. Lens-based fluorescence nanoscopy is poised for a high impact on
      future developments in the life sciences, with the potential to help solve long
      standing quests in different areas of scientific research. 

PMID- 25998829
TI  - Exceptional sensitivity to the synthetic approach and halogen substituent for
      Zn(II) coordination assemblies with 5-halonicotinic acids.
AB  - Seven Zn(II) coordination complexes with 5-halonicotinic acids (HL-X, X = F, Cl,
      or Br) have been synthesized with different synthetic approaches, including layer
      diffusion or stirring method in an ambient environment and solvothermal synthesis
      at 100  degrees C. Assembly of HL-F with Zn(II) under different conditions will
      yield the same 2D network of [Zn(L-F)2]n (1). Interestingly, three distinct
      complexes, a 3D framework {[Zn2(L-Cl)4(H2O)](H2O)6}n (2) and two 2D pseudo
      polymorphic isomers {[Zn(L-Cl)2](H2O)1.5}n (3) and {[Zn2(L-Cl)4](H2O)}n (4) can
      be obtained by reacting HL-Cl with Zn(II) under layer diffusion, stirring, and
      solvothermal conditions, respectively. Furthermore, replacing the -Cl substituent
      with -Br on the HL-X ligand will also afford three diverse coordination
      assemblies of 3D {[Zn2(L-Br)4(H2O)](CH3OH)2.5}n (5), mononuclear [Zn(HL
      Br)2(H2O)4][L-Br]2 (6), and 2D {[Zn(L-Br)2](H2O)1.15}n (7) depending on the
      synthetic pathways. Beyond the significant influence of the synthetic approach,
      which will lead to the formation of various crystalline products, the halogen
      substitution effect of HL-X ligands on the coordination motifs has also been
      demonstrated. In addition, thermal stability and fluorescence for these
      crystalline materials will be presented.

PMID- 25998827
TI  - MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by
      targeting SOCS1 in ulcerative colitis.
AB  - Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune
      responses, have been demonstrated in the colonic mucosa of patients with
      inflammatory bowel diseases (IBD), although its role in disease pathophysiology
      is unknown. We investigated the role of miR-155 in the acquisition and
      maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key
      cell population contributing to mucosal damage in IBD. IMF were isolated from
      colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn's disease
      (CD) patients. MiR-155 in IMF was quantified by quantitative reverse
      transcription-PCR in basal condition and following exposure to TNF-alpha,
      interleukin (IL)-1beta, lipopolysaccharide (LPS) or TGF-beta1. The effects of miR
      155 mimic or inhibitor transfection on cytokine release and suppressor of
      cytokine signaling 1 (SOCS1) expression were assessed by enzyme-linked
      immunosorbent assay and western blot, respectively. Regulation of the target gene
      SOCS1 expression by miR-155 was assessed using luciferase reporter construct. We
      found that miR-155 was significantly upregulated in UC as compared with control-
      and CD-derived IMF. Moreover, TNF-alpha and LPS, but not TGF-beta1 and IL-1beta,
      significantly increased miR-155 expression in IMF. Ectopic expression of miR-155
      in control IMF augmented cytokines release, whereas it downregulated SOCS1
      expression. MiR-155 knockdown in UC-IMF reduced cytokine production and enhanced
      SOCS1 expression. Luciferase reporter assay demonstrated that miR-155 directly
      targets SOCS1. Moreover, silencing of SOCS1 in control IMF significantly
      increased IL-6 and IL-8 release. In all, our data suggest that inflammatory
      mediators induce miR-155 expression in IMF of patients with UC. By downregulating
      the expression of SOCS1, miR-155 wires IMF inflammatory phenotype. 

PMID- 25998830
TI  - Pyrosequencing as a tool for the detection of Phytophthora species: error rate
      and risk of false Molecular Operational Taxonomic Units.
AB  - AIMS: To evaluate the accuracy of pyrosequencing for the description of
      Phytophthora communities in terms of taxa identification and risk of assignment
      for false Molecular Operational Taxonomic Units (MOTUs). METHODS AND RESULTS:
      Pyrosequencing of Internal Transcribed Spacer 1 (ITS1) amplicons was used to
      describe the structure of a DNA mixture comprising eight Phytophthora spp. and
      Pythium vexans. Pyrosequencing resulted in 16 965 reads, detecting all species in
      the template DNA mixture. Reducing the ITS1 sequence identity threshold resulted
      in a decrease in numbers of unmatched reads but a concomitant increase in the
      numbers of false MOTUs. The total error rate was 0.63% and comprised mainly
      mismatches (0.25%) CONCLUSIONS: Pyrosequencing of ITS1 region is an efficient and
      accurate technique for the detection and identification of Phytophthora spp. in
      environmental samples. However, the risk of allocating false MOTUs, even when
      demonstrated to be low, may require additional validation with alternative
      detection methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Phytophthora spp. are
      considered among the most destructive groups of invasive plant pathogens,
      affecting thousands of cultivated and wild plants worldwide. Simultaneous early
      detection of Phytophthora complexes in environmental samples offers an unique
      opportunity for the interception of known and unknown species along pathways of
      introduction, along with the identification of these organisms in invaded
      environments.

PMID- 25998831
TI  - Myeloid-derived suppressor cells suppress CD4+ and CD8+ T cell responses in
      autoimmune hepatitis.
AB  - Myeloid-derived suppressor cells (MDSCs) have been demonstrated with possess the
      ability to suppress T-cell responses. Therefore, MDSCs are an attractive
      candidate for immune intervention aimed at reconstituting self-tolerance in
      autoimmune conditions. The present study investigated the frequency and function
      of MDSCs in the peripheral blood of patients with autoimmune hepatitis (AIH), and
      examined its correlation with disease progression. Peripheral blood samples were
      obtained from 48 patients diagnosed with AIH and 24 healthy controls. The
      frequency of MDSCs was analyzed using flow cytometry, and its correlation with
      liver biochemical indicators was assessed. The sorted peripheral blood
      mononuclear cells and MDSCs, cocultivated with CD3 and CD28 monoclonal
      antibodies, were labeled with carboxylfluorescein succinimidyl ester and detected
      using flow cytometry for the proliferation of T cells. T cell apoptosis was
      detected using annexin V and 7-aminoactinomycin D. Interferon gamma and nitric
      oxide were detected using ELISA, and inducible nitric oxide synthase (iNOS) was
      detected using immunohistochemical staining. The frequency of MDSCs in the
      patients with non-cirrhotic AIH was significantly higher, compared with the
      healthy controls and patients with cirrhotic AIH (P<0.05). However, no
      significantly differences were observed between the patients with cirrhotic AIH
      and the healthy controls (P>0.05). In addition, the frequency of MDSCs in the
      peripheral blood was positively correlated with alanine transaminase and
      aspartate transaminase in patients with AIH. The T cells of the incubation system
      were suppressed by the MDSCs, which was associated with the iNOS expressed on
      MDSCs. In patients with non-cirrhotic AIH, the peripheral frequency of MDSCs was
      increased through a feedback loop and autoimmune responses were inhibited.
      However, a variety of causes led to a decrease in the number of MDSCs in patients
      with cirrhotic AIH, therefore, accelerating the progression of liver injury and
      liver cirrhosis.

PMID- 25998833
TI  - Association of Spectral-Domain Optical Coherence Tomography Findings with Visual
      Outcome of Macula-Off Rhegmatogenous Retinal Detachment Surgery.
AB  - PURPOSE: To identify prognostic factors for the visual outcome for patients with
      macula-off rhegmatogenous retinal detachment (RRD). METHODS: The medical records
      of 27 patients (27 eyes) with macula-off RRD were retrospectively investigated.
      In addition to clinical characteristics, spectral-domain optical coherence
      tomography (SD OCT) images were analyzed. RESULTS: The central foveal thickness
      at baseline was 923 +/- 499.5 um, and the mean height of the subretinal fluid was
      697.8 +/- 463.6 um. Dropout of backreflection at the fovea was detected on
      preoperative SD OCT in 8 patients (29.6%). The external limiting membrane was
      disrupted in 5 patients (18.5%) as was the photoreceptor integrity in 9 patients
      (33.3%) at 12 months. On multiple regression analysis, backreflection integrity
      was the only predictive factor for postoperative visual outcome (B = 0.179, p =
      0.020). CONCLUSIONS: Backreflection integrity on preoperative SD OCT seems to be
      helpful in predicting the postoperative visual outcome in macula-off RRD
      patients.

PMID- 25998832
TI  - Periplasmic superoxide dismutase SodCI of Salmonella binds peptidoglycan to
      remain tethered within the periplasm.
AB  - Salmonellae survive and propagate in macrophages to cause serious systemic
      disease. Periplasmic superoxide dismutase plays a critical role in this survival
      by combating phagocytic superoxide. Salmonella Typhimurium strain 14028 produces
      two periplasmic superoxide dismutases: SodCI and SodCII. Although both proteins
      are produced during infection, only SodCI is functional in the macrophage
      phagosome. We have previously shown that SodCI, relative to SodCII, is both
      protease resistant and tethered within the periplasm and that either of these
      properties is sufficient to allow a SodC to protect against phagocytic
      superoxide. Tethering is defined as remaining cell-associated after osmotic shock
      or treatment with cationic antimicrobial peptides. Here we show that SodCI non
      covalently binds peptidoglycan. SodCI binds to Salmonella and Bacillus
      peptidoglycan, but not peptidoglycan from Staphylococcus. Moreover, binding can
      be inhibited by a diaminopimelic acid containing tripeptide, but not a lysine
      containing tripeptide, showing that the protein recognizes the peptide portion of
      the peptidoglycan. Replacing nine amino acids in SodCII with the corresponding
      residues from SodCI confers tethering, partially delineating an apparently novel
      peptidoglycan binding domain. These changes in sequence increase the affinity of
      SodCII for peptidoglycan fragments to match that of SodCI and allow the now
      tethered SodCII to function during infection. 

PMID- 25998835
TI  - The effect of heparin on pregnancy associated plasma protein-A concentration in
      healthy, non-pregnant individuals.
AB  - OBJECTIVES: The objective of this study was to determine the differences in
      pregnancy associated plasma protein-A (PAPP-A) concentrations in heparin naive
      and heparin treated healthy men and non-pregnant women, to find a possible
      difference in different age groups, and to determine the response in PAPP-A
      concentration to repeated injections of unfractionated heparin. DESIGN AND
      METHODS: Twenty-five healthy, non-pregnant volunteers divided into five groups
      (determined by gender and age) received 5000 IU unfractionated heparin
      intravenously. Five young men received an additional 5000 IU after 90 and 180
      min. Blood samples to determine PAPP-A concentration and APTT were drawn at
      different time points. RESULTS: Injection of heparin elicited increase in and
      rapid normalization of PAPP-A concentrations in all subjects. The group of 20-30
      year-old never-pregnant women had lower responses than the individuals of the
      four other groups. The difference was not significant (p > 0.05). Repeated
      injections of heparin caused additional peaks in PAPP-A concentration of about
      the same sizes as the first peak. We observed an increase in time to
      normalization of PAPP-A concentration (from 75-90 min to 90-150 min) and APTT
      levels with repeated injections. CONCLUSIONS: We observed a rapid normalization
      of PAPP-A. Our result has a great similarity to the half-life of unfractionated
      heparin. This result combined with the finding of equally sized peaks in PAPP-A
      concentration, and that all of this was found in healthy, non-pregnant
      individuals, suggests that heparin might compete for a binding-site on PAPP-A or
      with PAPP-A itself for a common receptor in healthy arterial vessels.

PMID- 25998834
TI  - Interleukin-17 and innate immunity in infections and chronic inflammation.
AB  - Interleukin 17 (IL-17) includes several cytokines among which IL-17A is
      considered as one of the major pro-inflammatory cytokine being central to the
      innate and adaptive immune responses. IL-17 is produced by unconventional T
      cells, members of innate lymphoid cells (ILCs), mast cells, as well as typical
      innate immune cells, such as neutrophils and macrophages located in the
      epithelial barriers and characterised by a rapid response to infectious agents by
      recruiting neutrophils as first line of defence and inducing the production of
      antimicrobial peptides. Th17 responses appear pivotal in chronic and acute
      infections by bacteria, parasites, and fungi, as well as in autoimmune and
      chronic inflammatory diseases, including rheumatoid arthritis, psoriasis, and
      psoriatic arthritis. The data discussed in this review cumulatively indicate that
      innate-derived IL-17 constitutes a major element in the altered immune response
      against self antigens or the perpetuation of inflammation, particularly at
      mucosal sites. New drugs targeting the IL17 pathway include brodalumab,
      ixekizumab, and secukinumab and their use in psoriatic disease is expected to
      dramatically impact our approach to this systemic condition. 

PMID- 25998836
TI  - Melatonin decreases cell proliferation, impairs myogenic differentiation and
      triggers apoptotic cell death in rhabdomyosarcoma cell lines.
AB  - Melatonin is a small indole produced by the pineal gland and other tissues, and
      has numerous functions that aid in the maintenance of the whole body homeostasis,
      ranging from the regulation of circadian rhythms and sleep to protection from
      oxidative stress. Melatonin has also been reported to counteract cell growth and
      chemoresistance in different types of cancer. In the present study, we
      investigated the effects of exogenous melatonin administration on different human
      cell lines and primary mouse tumor cultures of rhabdomyosarcoma (RMS), the most
      frequent soft tissue sarcoma affecting childhood. The results showed that
      melatonin significantly affected the behavior of RMS cells, leading to inhibition
      of cell proliferation and impairment of myogenic differentiation followed by
      increased apoptotic cell death, as observed by immunoblotting analysis of
      apoptosis-related markers including Bax, Bcl-2 and caspase-3. Similar findings
      were observed using a combination of microscopy techniques, including
      scanning/transmission electron and confocal microscopy. Furthermore, melatonin in
      combination with doxorubicin or cisplatin, two compounds commonly used for the
      treatment of solid tumors, increased the sensitivity of RMS cells to apoptosis.
      These data indicated that melatonin may be effective in counteracting RMS tumor
      growth and chemoresistance. 

PMID- 25998837
TI  - Lysosomal storage of heparan sulfate causes mitochondrial defects, altered
      autophagy, and neuronal death in the mouse model of mucopolysaccharidosis III
      type C.
AB  - The genetic metabolic disease mucopolysaccharidosis III type C (MPS IIIC,
      Sanfilippo disease type C) causes progressive neurodegeneration in infants and
      children, leading to dementia and death before adulthood. MPS IIIC stands out
      among lysosomal diseases because it is the only one caused by a deficiency not of
      a hydrolase but of HGSNAT (heparan--glucosaminide N-acetyltransferase), which
      catalyzes acetylation of glycosaminoglycan heparan sulfate (HS) prior to its
      hydrolysis.

PMID- 25998838
TI  - Transcriptome analysis of BmN cells following over-expression of BmSTAT.
AB  - The Janus kinase/signal transducers and activators of transcription (JAK/STAT)
      signaling pathway are involved in immune response, cell proliferation,
      differentiation, cell migration and apoptosis. In order to better understand the
      role of the JAK/STAT pathway in insects we chose Bombyx mori as an experimental
      model system. Over-expression of BmSTAT in a BmN cell line increased the number
      of cells in the G2 phase of the cell cycle. Genome-wide transcriptome analysis
      was performed to identify genes that were differentially expressed following
      BmSTAT overexpression. Transcriptome data showed that 10,853 and 10,129 expressed
      genes were obtained from the normal BmN cells and transformed cells,
      respectively. A total of 800 differentially expressed genes (DEGs) were detected,
      of which 787 were up-regulated and 13 were down-regulated with T test. In case of
      FC-test, 252 DEGs were detected, and 123 were expressed in the transformed cells
      and remaining were in the normal cells. Gene ontology (GO) annotation predicted a
      functional role for DEGs in catalytic activity, binding, transport, biological
      regulation, cellular and metabolic processes and pigmentation, while Kyoto
      encyclopedia of genes and genomes (KEGG) analysis revealed the affected genes to
      be involved in a multitude of cell signaling pathways. Our findings implicate
      JAK/STAT signaling in regulating the cell cycle in Bombyx mori, probably in
      combination with other pathways. These findings justify further investigation
      into the functional role of the BmSTAT gene. 

PMID- 25998839
TI  - Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in
      hepatocellular carcinoma by control of epithermal growth factor receptor-induced
      epithelial-mesenchymal transition.
AB  - Hepatocellular carcinoma (HCC) is the third-most lethal cancer worldwide.
      Understanding the molecular pathogenesis of HCC recurrence and metastasis is the
      key to improve patients' prognosis. In this study, we report that protein
      tyrosine phosphatase receptor S (PTPRS) is significantly down-regulated in nearly
      80% of HCCs, and its expression negatively correlates with aggressive
      pathological features, such as larger tumor size and advanced stage. In addition,
      PTPRS deficiency is independently associated with shorter survival and increased
      recurrence in patients, although 16.7% of HCCs show intratumor heterogeneous
      expression of PTPRS. Restoration of wild-type, but not mutant, PTPRS expression
      significantly inhibits HCC cell migration and invasion in vitro as well as lung
      metastasis in vivo, whereas knockdown of its expression significantly promotes
      invasion and metastasis. Notably, PTPRS-regulated HCC invasiveness is accompanied
      by typical changes of epithelial-mesenchymal transition (EMT). Moreover, PTPRS
      forms a complex with epithermal growth factor receptor (EGFR) and regulates its
      tyrosine residues' phosphorylation. Ectopic expression of EGFR reverses the
      metastasis-inhibiting effects of PTPRS, whereas silencing of EGFR or inhibiting
      phosphorylation of key molecules in EGFR downstream pathways reinhibits EMT and
      metastasis caused by PTPRS down-regulation. Meanwhile, promoter hypermethylation
      of PTPRS is frequently detected in HCC samples and cell lines. Treatment with a
      demethylation agent, 5-aza-2'-deoxycytidine, recovers PTPRS expression in a dose
      dependent manner. CONCLUSIONS: Epigenetic inactivation of PTPRS may increase
      phosphorylation and activity of EGFR signaling to promote EMT and metastasis in
      HCC.

PMID- 25998840
TI  - Observation of terahertz-radiation-induced ionization in a single nano island.
AB  - Terahertz (THz) electromagnetic wave has been widely used as a spectroscopic
      probe to detect the collective vibrational mode in vast molecular systems and
      investigate dielectric properties of various materials. Recent technological
      advances in generating intense THz radiation and the emergence of THz plasmonics
      operating with nanoscale structures have opened up new pathways toward THz
      applications. Here, we present a new opportunity in engineering the state of
      matter at the atomic scale using THz wave and a metallic nanostructure. We show
      that a medium strength THz radiation of 22 kV/cm can induce ionization of ambient
      carbon atoms through interaction with a metallic nanostructure. The prepared
      structure, made of a nano slot antenna and a nano island located at the center,
      acts as a nanogap capacitor and enhances the local electric field by two orders
      of magnitudes thereby causing the ionization of ambient carbon atoms. Ionization
      and accumulation of carbon atoms are also observed through the change of the
      resonant condition of the nano slot antenna and the shift of the characteristic
      mode in the spectrum of the transmitted THz waves.

PMID- 25998841
TI  - NCI-H295R cell line as in vitro model of hyperaldosteronism lacks functional
      KCNJ5 (GIRK4; Kir3.4) channels.
AB  - As a major cause of aldosterone producing adenomas, numerous gain-of-function
      mutations in the KCNJ5 gene (encoding the K(+) channel subunit GIRK4) have been
      identified. The human adrenocortical carcinoma cell line NCI-H295R is the most
      frequently used cellular model for in vitro studies related to regulation of
      aldosterone-synthesis. Because of the undefined role of KCNJ5 (GIRK4) in
      regulating synthesis of aldosterone, we aimed at identifying basal and G protein
      activated GIRK4 currents in this paradigmatic cell line. The GIRK-specific
      blocker Tertiapin-Q did not affect basal current. Neither loading of the cells
      with GTP-gamma-S via the patch-clamp pipette nor agonist stimulation of an
      infected A1-adenosine receptor resulted in activation of GIRK current. In cells
      co-infected with KCNJ5, robust activation of basal and adenosine-activated inward
      rectifying current was observed. Although GIRK4 protein can be detected in
      Western blots of H295R homogenates, we suggest that GIRK4 in aldosterone
      producing cells does not form functional G(betagamma)-activated channels.

PMID- 25998842
TI  - Strengthening of hearing ear representation reduces binaural sensitivity in early
      single-sided deafness.
AB  - Single-sided deafness initiates extensive adaptations in the central auditory
      system, with the consequence that a stronger and a weaker ear representation
      develops in the auditory brain. Animal studies demonstrated that the effects are
      substantially stronger if the condition starts early in development. Sequential
      binaural cochlear implantations with longer interimplant delays demonstrate that
      the speech comprehension at the weaker ear is substantially compromised. A
      pronounced loss of the ability to extract and represent binaural localisation
      cues accompanies this condition, as shown in animal models.

PMID- 25998843
TI  - The Anti-Microbial Peptide LL-37/CRAMP Is Elevated in Patients with Liver
      Diseases and Acts as a Protective Factor during Mouse Liver Injury.
AB  - BACKGROUND: Antimicrobial peptides (AMP) are an important defense mechanism of
      the innate immune system and can modulate the course of various diseases.
      However, their significance during liver pathogenesis is currently not well
      defined. METHODS: Patients with liver diseases were analyzed for LL-37/CRAMP,
      human beta-defensin-2 (hBD2), and complement 5a (C5a) serum levels. Mice
      deficient in CRAMP (Cathelicidin-related Antimicrobial Peptide), the mouse
      homolog for human LL-37, were fed with a methionine- and choline-deficient diet
      (MCD) and underwent bile-duct ligation (BDL). RESULTS: First, serum samples from
      patients with chronic liver diseases were investigated. Therefore, significantly
      enhanced levels for LL-37, hBD2, and complement C5a were detected, all of which
      comprise antimicrobial properties. Next, CRAMP-knockout (CRAMP-KO) mice were
      investigated, to better define a functional role of LL-37/CRAMP in animal models
      of liver diseases. MCD feeding and bile-duct ligation of CRAMP-KO mice resulted
      in an enhanced degree of liver injury during the early treatment phase. MCD
      feeding in CRAMP-KO mice led to stronger intrahepatic fat accumulation and
      significantly enhanced matrix remodeling, whereas BDL caused more extensive liver
      necrosis. At the late 28 days time point, MCD-fed CRAMP-KO mice displayed a
      higher intrahepatic fat load. Long-term changes in bile-duct-ligated mice
      included higher collagen content as a sign of enhanced fibrosis progression if
      CRAMP was absent. CONCLUSION: The study shows a clear correlation of
      antimicrobial peptide serum levels in patients with chronic liver diseases.
      Furthermore, we were able to demonstrate protective functions of LL-37/CRAMP in
      two independent mouse models of chronic liver injury.

PMID- 25998844
TI  - Variants of Base Excision Repair Genes MUTYH , PARP1 and XRCC1 in Alzheimer's
      Disease Risk.
AB  - BACKGROUND: Many clinical studies have shown that oxidative stress pathways and
      the efficiency of the oxidative DNA damage base excision repair (BER) system are
      associated with the pathogenesis of Alzheimer's disease (AD). Reduced BER
      efficiency may result from polymorphisms of BER-related genes. In the present
      study, we examine whether single nucleotide polymorphisms (SNPs) of BER genes are
      associated with increased risk of AD. METHODS: SNP genotyping was carried out on
      DNA isolated from peripheral blood mononuclear cells obtained from 120 patients
      with AD and 110 healthy volunteers. Samples were genotyped for the presence of
      BER-related SNPs, i.e. XRCC1-rs1799782, rs25487; MUTYH-rs3219489, and PARP1
      rs1136410. RESULTS: We found a positive association between AD risk and the
      presence of G/A genotype variant of the XRCC1 rs25487 polymorphism [odds ratio
      (OR) = 3.762, 95% CI: 1.793-7.891]. The presence of the A/A genotype of this
      polymorphism reduced the risk of AD (OR = 0.485, 95% CI: 0.271-0.870). In cases
      of the PARP1 gene rs1136410 polymorphism, we observed that the T/C variant
      increases (OR = 4.159, 95% CI: 1.978-8.745) while the T/T variant reduces risk
      (OR = 0.240, 95% CI: 0.114-0.556) of AD. CONCLUSIONS: We conclude that BER gene
      polymorphisms may play an important role in the etiology of AD. Diagnosing the
      presence or absence of particular genetic variants may be an important marker of
      AD. Further research on a larger population is needed. There is also a need to
      examine polymorphisms of other BER in the context of AD risk.

PMID- 25998845
TI  - Molecular and cellular mechanisms of tight junction dysfunction in the irritable
      bowel syndrome.
AB  - The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of
      the most prevalent gastrointestinal disorders, are complex and have not been
      fully elucidated. The present study aimed to investigate the molecular and
      cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues
      of IBS and non-IBS patients were examined to observe cellular changes by cell
      chemical tracer electron microscopy and transmission electron microscopy, and
      intestinal claudin-1 protein was detected by immunohistochemistry, western blot
      analysis and fluorescence quantitative polymerase chain reaction. Compared with
      the control group, TJ broadening and the tracer extravasation phenomenon were
      observed in the diarrhea-predominant IBS group, and a greater number of
      neuroendocrine cells and mast cells filled with high-density particles in the
      endocrine package pulp as well as a certain extent of vacuolization were present.
      The expression of claudin-1 in diarrhea-predominant IBS patients was decreased,
      while it was increased in constipation-predominant IBS patients. In conclusion,
      the results of the present study indicated that changes in cellular structure and
      claudin-1 levels were associated with Tjs in IBS. 

PMID- 25998846
TI  - Effects of fully accessible magnetic resonance imaging in the emergency
      department.
AB  - BACKGROUND: The Joint Commission Comprehensive Stroke Center certification
      requires that magnetic resonance imaging (MRI) be available on site, 24 hours a
      day, 7 days a week for evaluation of stroke in emergency department (ED)
      patients. Increased access to advanced diagnostic imaging has been shown to
      increase utilization, ED length of stay (LOS), and health care costs. EDs
      nationwide face decisions to pursue certification and increase MRI access.
      Understanding changes in utilization and the downstream effects may inform these
      decisions. OBJECTIVES: The objective was to determine changes in emergency MRI
      utilization following placement of a 24/7 accessible MRI in the ED and its
      effects on resource utilization for rule-out stroke and neurology consult
      patients. METHODS: This was a retrospective cohort study comparing MRI use during
      the 32 months before and 26 months after MRI acquisition period in the ED of a
      Level I trauma and stroke center. An interrupted time-series design was used to
      account for changes in clinical practice patterns following MRI acquisition. Time
      series plots and segmented regression analyses are presented to compare
      utilization patterns pre- and post-MRI and to understand potential confounding
      due to secular trends. Statistical hypothesis testing was used to determine
      differences in utilization, demographics, and clinical characteristics for
      cohorts pre- and post-MRI. RESULTS: MRI utilization in the ED increased 38.4% for
      rule-out stroke and 51.4% for neurology consult patients after MRI acquisition.
      The proportion of rule-out stroke patients receiving MRI increased from 32.5% pre
      MRI to 45.0% post-MRI (p < 0.001). The proportion of neurology consult patients
      increased from 32.6% pre-MRI to 49.4% post-MRI (p < 0.001). Considering baseline
      increases in MRI utilization rates for both cohorts over time, segmented
      regression models detected more substantial and significant changes in
      utilization after MRI acquisition for the larger neurology cohort (p < 0.001)
      compared to the rule-out stroke cohort (p = 0.095). However, hospital admission
      rates declined 16.7% for rule-out stroke patients (68.2% pre, 56.8% post; p <
      0.001) and remained constant for neurology patients (56.5% pre, 57.5% post; p =
      0.414). Patients who obtained MRI in the ED had increased ED LOS, but decreased
      hospital LOS (admitted patients), compared to those with no MRI for pre and post
      cohorts. CONCLUSIONS: Emergency MRI utilization increased substantially after
      placement of a fully accessible MRI in the ED. Patients receiving emergency MRI
      had increased ED LOS, decreased admission rates for some patients (rule-out
      stroke), and reduced hospital LOS for those admitted. Potential changes in ED
      patient resource utilization should be considered when determining whether to
      acquire an MRI for Comprehensive Stroke Center certification.

PMID- 25998847
TI  - miR-25 targets the modulator of apoptosis 1 gene in lung cancer.
AB  - To determine the role of miR-25 in non-small cell lung cancer (NSCLC), we first
      detected miR-25 expression in clinical specimens and lung cancer cell lines by
      quantitative real-time polymerase chain reaction. The levels of miR-25 were
      elevated in the plasma of NSCLC patients and NSCLC cell lines. Transfection of
      A549 and 95-D cells with a miR-25 inhibitor resulted in reduced cell
      proliferation and enhanced apoptosis. Moreover, the modulator of apoptosis 1
      (MOAP1) gene was identified as a novel target of miR-25. The ability of miR-25 to
      promote cell proliferation and block apoptosis is attributable to its effect on
      MOAP1 suppression. In addition, miR-25 antagomir significantly inhibited lung
      cancer growth via upregulation of MOAP1 in a mouse xenograft model. Collectively,
      these data demonstrate that miR-25 is an important biomarker for lung cancer, and
      miR-25 promotes cell proliferation and inhibits apoptosis in NSCLC cells by
      negatively regulating MOAP1 expression. 

PMID- 25998848
TI  - Lipoic acid inhibits the DNA repair protein O 6-methylguanine-DNA
      methyltransferase (MGMT) and triggers its depletion in colorectal cancer cells
      with concomitant autophagy induction.
AB  - Alkylating agents are present in food and tobacco smoke, but are also used in
      cancer chemotherapy, inducing the DNA lesion O (6)-methylguanine. This critical
      adduct is repaired by O (6)-methylguanine-DNA methyltransferase (MGMT), resulting
      in MGMT inactivation and degradation. In the present study, we analyzed the
      effects of the natural disulfide compound lipoic acid (LA) on MGMT in vitro and
      in colorectal cancer cells. We show that LA, but not its reduced form
      dihydrolipoic acid, potently inhibits the activity of recombinant MGMT by
      interfering with its catalytic Cys-145 residue, which was partially reversible by
      N-acetyl cysteine. Incubation of HCT116 colorectal cancer cells with LA altered
      their glutathione pool and caused a decline in MGMT activity. This was mirrored
      by LA-induced depletion of MGMT protein, which was not attributable to changes in
      MGMT messenger RNA levels. Loss of MGMT protein coincided with LA-induced
      autophagy, a process resulting in lysosomal degradation of proteins, including
      presumably MGMT. LA-stimulated autophagy in a p53-independent manner as revealed
      by the response of isogenic HCT116 cell lines. Knockdown of the crucial autophagy
      component beclin-1 and chemical inhibitors blocked LA-induced autophagy, but did
      not abrogate LA-triggered MGMT degradation. Concomitant with MGMT depletion, LA
      pretreatment resulted in enhanced O (6)-methylguanine levels in DNA. It also
      increased the cytotoxicity of the alkylating anticancer drug temozolomide in
      temozolomide-resistant colorectal cancer cells. Taken together, our study showed
      that the natural compound LA inhibits MGMT and induces autophagy. Furthermore, LA
      enhanced the cytotoxic effects of temozolomide, which makes it a candidate for a
      supplement in cancer therapy. 

PMID- 25998850
TI  - Acid reflux and head and neck cancer risk: A nationwide registry over 13 years.
AB  - OBJECTIVE: Gastro-esophageal reflux disease (GERD) is a highly prevalent
      disorder; however, important questions remain regarding the link between GERD and
      extra-esophageal cancers. This nationwide cohort study investigated the risk of
      developing head and neck cancers (HNCs) among patients with GERD. METHODS: Newly
      diagnosed GERD patients aged >=20 years without antecedent cancer were included.
      Case data were obtained from the National Health Insurance Research Database
      covering period from 1998 to 2010. We compared the standardized incidence ratios
      (SIRs) of cancer among GERD patients with those of the general population.
      RESULTS: A total of 98 cancers were identified among the 39,845 GERD patients in
      the study, representing 128,361 person-years. The SIR for all cases of cancer was
      1.59 (95% CI 1.29-1.93). GERD patients exhibited significantly higher SIRs for
      oropharyngeal (SIR 3.58, 95% CI 1.85-6.25) and hypopharyngeal (SIR 3.96, 95% CI
      2.35-6.26) cancers. Male patients had a significantly higher risk of HNCs (SIR
      1.70, 95% CI 1.36-2.10), particularly oropharyngeal (SIR 4.01, 95% CI 2.00-7.17)
      and hypopharyngeal (SIR 3.91, 95% CI 2.28-6.26) cancers. Following adjustment for
      age and co-morbidities, the hazard ratio was 9.06 (95% CI 4.70-17.44) for males
      compared to females. CONCLUSION: There may be a potential association between
      GERD and risk of HNCs, which however merits further studies to confirm the causal
      relationship. Our observations indicate a need for careful extra-esophageal
      examination of patients with acid reflux. Our findings also underline the
      importance of raising awareness among clinicians regarding the possibility of
      concurrent HNCs in GERD patients with refractory laryngo-pharyngeal symptoms.

PMID- 25998851
TI  - Primary adenoid cystic carcinoma of the nasolacrimal duct treated with proton
      beam therapy.
AB  - Primary malignant tumors of the lacrimal passage, particularly of the
      nasolacrimal duct, are rare. We describe a 72-year-old woman who presented with
      lacrimation 5 years previously. She had pain and bloody and purulent lacrimation,
      and a mass was identified in the inferior meatus. Accordingly, she was diagnosed
      with primary adenoid cystic carcinoma of the nasolacrimal duct. She was treated
      with proton beam therapy and showed a favorable response. Owing to the long-term
      risks of recurrence and distant metastasis, adenoid cystic carcinoma requires
      sufficient follow-up. 

PMID- 25998849
TI  - Processing Body Formation Limits Proinflammatory Cytokine Synthesis in Endotoxin
      Tolerant Monocytes and Murine Septic Macrophages.
AB  - An anti-inflammatory phenotype with pronounced immunosuppression develops during
      sepsis, during which time neutrophils and monocytes/macrophages limit their Toll
      like receptor 4 responses to bacterial lipopolysaccharide (LPS/endotoxin). We
      previously reported that during this endotoxin-tolerant state, distinct signaling
      pathways differentially repress transcription and translation of proinflammatory
      cytokines such as TNFalpha and IL-6. Sustained endotoxin tolerance contributes to
      sepsis mortality. While transcription repression requires chromatin
      modifications, a translational repressor complex of Argonaute 2 (Ago2) and RNA
      binding motif protein 4 (RBM4), which bind the 3'-UTR of TNFalpha and IL-6 mRNA,
      limits protein synthesis. Here, we show that Dcp1 supports the assembly of the
      Ago2 and RBM4 repressor complex into cytoplasmic processing bodies (p-bodies) in
      endotoxin-tolerant THP-1 human monocytes following stimulation with LPS,
      resulting in translational repression and limiting protein synthesis.
      Importantly, this translocation process is reversed by Dcp1 knockdown, which
      restores TNFalpha and IL-6 protein levels. We also find this translational
      repression mechanism in primary macrophages of septic mice. Because p-body
      formation is a critical step in mRNA translation repression, we conclude that
      Dcp1 is a major component of the translational repression machinery of endotoxin
      tolerance and may contribute to sepsis outcome. 

PMID- 25998852
TI  - Conservation in Europe as a Model for Emerging Conservation Issues Globally.
      Introduction.

PMID- 25998853
TI  - Protomyofibroblast Pathway in Early Thermal Burn Healing.
AB  - Wound healing following partial thickness thermal burns is commonly hampered by
      the risk of hypertrophic scarring. Skin myofibroblast (MF) density is commonly
      increased in postburn healing. The transition between fibroblast-like cells and
      alpha-smooth muscle actin (SMA)+ MF possibly begins with CD14+ monocytes,
      evolving to CD14+ CD34+ fibrocytes, followed by beta-SMA+ protomyofibroblast
      (PMF) maturation. Skin biopsies from 25 burn patients were collected about 1 and
      4 weeks after injury. Immunohistochemistry was performed using monoclonal
      antibodies to alpha-SMA, beta-SMA, factor XIIIa, lysozyme, Mac 387, CD14, CD117
      and Ulex europaeus agglutinin-1 (UEA-1). The set of Mac 387+ and CD14+ monocytes
      was accompanied by both CD34+ fibrocytes and factor XIIIa+ dendrocytes. By
      contrast, beta-SMA+ PMF were rare. Of note, alpha-SMA+ MF were more abundant at
      week 4 than at week 1 (p < 0.01). The UEA-1+ endothelial cells showed marked
      variations in their dermal distribution, irrespective of the densities in the
      other scrutinized cells. In conclusion, healing of partial thickness thermal
      burns involves a diversity of cell types including PMF. In the present samples,
      the PMF density remained low. (c) 2015 S. Karger AG, Basel. 

PMID- 25998854
TI  - Novel Multipin Electrode Cap System for Dry Electroencephalography.
AB  - Current usage of electroencephalography (EEG) is limited to laboratory
      environments. Self-application of a multichannel wet EEG caps is practically
      impossible, since the application of state-of-the-art wet EEG sensors requires
      trained laboratory staff. We propose a novel EEG cap system with multipin dry
      electrodes overcoming this problem. We describe the design of a novel 24-pin dry
      electrode made from polyurethane and coated with Ag/AgCl. A textile cap system
      holds 97 of these dry electrodes. An EEG study with 20 volunteers compares the 97
      channel dry EEG cap with a conventional 128-channel wet EEG cap for resting state
      EEG, alpha activity, eye blink artifacts and checkerboard pattern reversal visual
      evoked potentials. All volunteers report a good cap fit and good wearing comfort.
      Average impedances are below 150 kOmega for 92 out of 97 dry electrodes, enabling
      recording with standard EEG amplifiers. No significant differences are observed
      between wet and dry power spectral densities for all EEG bands. No significant
      differences are observed between the wet and dry global field power time courses
      of visual evoked potentials. The 2D interpolated topographic maps show
      significant differences of 3.52 and 0.44% of the map areas for the N75 and N145
      VEP components, respectively. For the P100 component, no significant differences
      are observed. Dry multipin electrodes integrated in a textile EEG cap overcome
      the principle limitations of wet electrodes, allow rapid application of EEG
      multichannel caps by non-trained persons, and thus enable new fields of
      application for multichannel EEG acquisition.

PMID- 25998855
TI  - A Comparison of Independent Component Analysis (ICA) of fMRI and Electrical
      Source Imaging (ESI) in Focal Epilepsy Reveals Misclassification Using a
      Classifier.
AB  - Interictal epileptiform discharges (IEDs) can produce haemodynamic responses that
      can be detected by electroencephalography-functional magnetic resonance imaging
      (EEG-fMRI) using different analysis methods such as the general linear model
      (GLM) of IEDs or independent component analysis (ICA). The IEDs can also be
      mapped by electrical source imaging (ESI) which has been demonstrated to be
      useful in presurgical evaluation in a high proportion of cases with focal IEDs.
      ICA advantageously does not require IEDs or a model of haemodynamic responses but
      its use in EEG-fMRI of epilepsy has been limited by its ability to separate and
      select epileptic components. Here, we evaluated the performance of a classifier
      that aims to filter all non-BOLD responses and we compared the spatial and
      temporal features of the selected independent components (ICs). The components
      selected by the classifier were compared to those components selected by a strong
      spatial correlation with ESI maps of IED sources. Both sets of ICs were
      subsequently compared to a temporal model derived from the convolution of the
      IEDs (derived from the simultaneously acquired EEG) with a standard haemodynamic
      response. Selected ICs were compared to the patients' clinical information in 13
      patients with focal epilepsy. We found that the misclassified ICs clearly related
      to IED in 16/25 cases. We also found that the classifier failed predominantly due
      to the increased spectral range of fMRIs temporal responses to IEDs. In
      conclusion, we show that ICA can be an efficient approach to separate responses
      related to epilepsy but that contemporary classifiers need to be retrained for
      epilepsy data. Our findings indicate that, for ICA to contribute to the analysis
      of data without IEDs to improve its sensitivity, classification strategies based
      on data features other than IC time course frequency is required.

PMID- 25998856
TI  - Intracellular leptin signaling following effective weight loss.
AB  - AIM: To investigate the effect of ex-vivo leptin treatment before and after
      weight loss on key-molecules of intracellular leptin signaling in peripheral
      blood mononuclear cells (PBMCs) of obese women. MATERIALS AND METHODS: Five
      healthy obese women underwent a 12-week medical nutrition treatment aiming at
      inducing 10% weight loss. Isolated PBMCs at baseline, and at weeks 8 and 12 were
      treated with increasing leptin doses (0, 25 and 75 ng/ml) for 30 min. The
      phosphorylation of signal transducer and activator of transcription (STAT)3,
      extracellular-signal-regulated kinase (ERK), protein kinase B (Akt) and 5'
      adenosine monophosphate-activated protein kinase (AMPK) of PBMCs was analyzed
      using Western blotting. RESULTS: Women lost 10 +/- 1% and 13 +/- 1% of weight at
      week 8 and 12, respectively. Circulating leptin and insulin significantly
      decreased from 39.5 +/- 7.7 to 12.2 +/- 2.4 ng/ml (p = 0.026) and from 13.0 +/-
      1.6 to 5.4 +/- 0.9 MUU/ml (p = 0.005) at week 12, respectively. In the ex vivo
      study, a significant decrease in STAT3 phosphorylation was observed in the
      control group after weight loss. Treatment of PBMCs with leptin 75 ng/ml
      increased significantly ERK, STAT3 and Akt phosphorylation, but no weight loss
      induced change was observed in response to leptin treatment ex vivo. CONCLUSIONS:
      A 10%-15% weight loss decreases baseline STAT3 phosphorylation ex vivo, but does
      not alter the effect of increasing doses of leptin on the incremental
      intracellular phosphorylation of STAT3, ERK, Akt and AMPK. Supraphysiologic
      leptin doses (75 ng/ml) result in higher protein phosphorylation compared to
      either physiologic doses or no treatment, before and after weight loss.

PMID- 25998857
TI  - Iptakalim protects against ischemic injury by improving neurovascular unit
      function in the mouse brain.
AB  - It has been reported that the novel ATP-sensitive potassium (K-ATP) channel
      opener iptakalim (IPT) decreases ischemic neuronal damage in rats. However, the
      mechanisms underlying neuroprotection are still to be fully elucidated. The
      results of this study showed that mice with ischemia induced by middle cerebral
      artery occlusion exhibited higher mortality and more neurological deficits, as
      well as larger infarct volume, compared with sham mice. Moreover, it was found
      that ischemia activated astrocytes surrounding CA1 neurons with an increased
      expression of D-serine, induced greater microglial activation accompanied by
      higher tumor necrosis factor alpha (TNF-alpha) production, and caused higher
      expressions of matrix metalloproteinase 9 (MMP-9) in the endothelial cells of
      mice. Pretreatment with IPT significantly attenuated the neurological deficits
      and decreased the infarct volume in mice. IPT treatment could decrease MMP-9
      secretion, inhibit astrocytic activation with decreasing D-serine and elevating
      connexin43 expression. Microglial activation was also inhibited and TNF-alpha
      production was decreased by IPT. Taken together, a K-ATP channel opener may
      improve the function of neurovascular unit and protect against ischemic injury.
      These findings suggest that targeting K-ATP channels provides a promising
      therapeutic approach for stroke. 

PMID- 25998858
TI  - Effect of summer conditions and shade on the production and metabolism of
      Holstein dairy cows on pasture in temperate climate.
AB  - For dairy cattle on pasture in temperate regions, it is largely unknown to what
      degree hot summer conditions impact energy metabolism, milk yield and milk
      composition and how effective shade is in reducing these negative effects. During
      the summer of 2012, a herd of Holstein cows was kept on pasture without access to
      shade (treatment NS). During the summers of 2011 and 2013, the herd was divided
      into a group with (treatment S) and a group without (treatment NS) access to
      shade. Shade was provided by young trees combined with shade cloths (80%
      reduction in solar radiation). A weather station registered the local climatic
      conditions on open pasture, from which we calculated daily average Heat Load
      Index (HLI) values. The effects of HLI and shade on rectal temperature (RT),
      blood plasma indicators of hyperventilation and metabolic changes due to heat
      stress, milk yield and milk composition were investigated. RT increased with
      increasing HLI, but was less for S cows than for NS cows (by 0.02 degrees C and
      0.03 degrees C increase per unit increase of HLI, respectively). Hyperchloraemia
      (an increased blood plasma concentration of Cl-), a sign of hyperventilation,
      increased for NS cows but not for S cows. The plasma concentration of alkaline
      phosphatase, a regulator of energy metabolism in the liver, decreased with
      increasing HLI for NS cows only. Access to shade, thus, reduced the effect of HLI
      on RT, hyperchloraemia and the regulation of metabolism by the liver. As HLI
      increased, the plasma concentration of cholesterol decreased (indicating
      increased lipolysis) and the plasma concentration of creatinine increased
      (indicating increased protein catabolism). These effects did not differ between S
      and NS cows. For NS cows, after a lag-time of 2 days, the milk yield decreased
      with increasing HLI. For S cows, the milk yield was unaffected by HLI and its
      quadratic factor. The milk concentrations of lactose, protein and fat decreased
      as HLI increased, but only the effect on milk protein content was remediated by
      shade. In conclusion, access to shade tempered the negative effects of high HLI
      on RT, hyperchloraemia and a blood plasma indicator of changing energy metabolism
      (generally) as well as prevented the decrease in milk yield observed in cows
      without access to shade. 

PMID- 25998859
TI  - Teaching cataract surgery to trainees in the operating theatre.

PMID- 25998860
TI  - The histone methyltransferase EZH2 promotes mammary stem and luminal progenitor
      cell expansion, metastasis and inhibits estrogen receptor-positive cellular
      differentiation in a model of basal breast cancer.
AB  - Mammary stem cells (MSCs) are the progenitor population for human breast
      epithelia. MSCs give rise during mammary gland development to estrogen receptor
      (ER)-negative basal cells and the ER- luminal progenitor (LP) population which
      maintains ER+ and ER- luminal cells. The MSC population is expanded and
      tumorigenic in some mouse mammary cancer models, and these tumor-initiating cells
      have been isolated from human breast cancers. MSC expansion is associated with
      aggressive biological behavior in human breast cancer. The LP population is
      tumorigenic in some mouse mammary cancer models, and is the progenitor population
      of basal breast cancer in humans. The enhancer of zeste homolog 2 (EZH2) is a
      methyltransferase which catalyzes lysine 27 methylation in histone H3 resulting
      in suppression of target gene expression. The histone demethylase JMJD3 opposes
      the activity of EZH2 by demethylating histone H3 lysine 27. EZH2 is a member of
      the polycomb group of proteins which regulates cell type identity. EZH2
      expression was found to be increased in histologically normal human breast tissue
      among women with high breast cancer risk, and was elevated in ductal hyperplasia
      and ductal carcinoma in situ. EZH2 overexpression is associated with poorly
      differentiated and aggressive breast cancer in humans. However, the mechanisms by
      which EZH2 results in increased breast cancer risk and aggressive tumors are not
      completely characterized. Using in vivo transplantation of mammary cancer stem
      cells transduced with EZH2 or JMJD3 shRNAs, we demonstrated that EZH2 promotes
      mammary stem and LP cell expansion, metastasis and inhibits ER-positive cellular
      differentiation.

PMID- 25998861
TI  - Quantifying Search Dog Effectiveness in a Terrestrial Search and Rescue
      Environment.
AB  - OBJECTIVE: There is widespread and longstanding use of dogs in land search and
      rescue (SAR) operations, and their effectiveness is well accepted within the SAR
      community. However, very little published research exists that quantifies that
      effectiveness within a realistic SAR environment. METHODS: This study included 25
      experiments, conducted between October 2013 and February 2014 with 10 dog/handler
      pairs, using randomized target placement to calculate the ratio of hits, misses,
      and false positives per dog. Each dog was fitted with a GPS receiver to record
      their paths and ambient temperature. Wind strength and humidity were recorded
      throughout each run. RESULTS: There was no identifiable correlation between
      humidity, temperature, or wind speed and effectiveness, but the age of the dog
      has a small positive correlation. Using a standard effectiveness formula, basic
      descriptive statistics were generated, which showed that the dogs tested were
      76.4% successful overall, with an effectiveness of 62.9%. Dogs covered a mean
      distance 2.4 times greater than their human handlers but travelled at roughly
      average human walking speed. CONCLUSIONS: This work represents a first attempt to
      quantify and understand levels of performance in lowland search dogs, and these
      results need to be understood within that context. A repeatable experimental
      framework has been demonstrated and provides a foundation for further work in
      this area.

PMID- 25998862
TI  - In Response to How Not To Train Your Dragon: A Case of Komodo Dragon Bite, by
      Borek and Charlton.

PMID- 25998865
TI  - Daily sodium and potassium excretion can be estimated by scheduled spot urine
      collections.
AB  - AIM: The evaluation of sodium and potassium intake is part of the optimal
      management of hypertension, metabolic syndrome, renal stones, and other
      conditions. To date, no convenient method for its evaluation exists, as the gold
      standard method of 24-hour urine collection is cumbersome and often incorrectly
      performed, and methods that use spot or shorter collections are not accurate
      enough to replace the gold standard. The aim of this study was to evaluate the
      correlation and agreement between a new method that uses multiple-scheduled spot
      urine collection and the gold standard method of 24-hour urine collection.
      METHODS: The urine sodium or potassium to creatinine ratios were determined for
      four scheduled spot urine samples. The mean ratios of the four spot samples and
      the ratios of each of the single spot samples were corrected for estimated
      creatinine excretion and compared to the gold standard. RESULTS: A significant
      linear correlation was demonstrated between the 24-hour urinary solute excretions
      and estimated excretion evaluated by any of the scheduled spot urine samples. The
      correlation of the mean of the four spots was better than for any of the single
      spots. Bland-Altman plots showed that the differences between these measurements
      were within the limits of agreement. CONCLUSION: Four scheduled spot urine
      samples can be used as a convenient method for estimation of 24-hour sodium or
      potassium excretion.

PMID- 25998864
TI  - Vismodegib induces significant clinical response in locally advanced
      trichoblastic carcinoma.
AB  - Patients with advanced basal cell carcinoma due to local extension or metastatic
      disease were previously at a therapeutic impasse. Targeted inhibition of the
      sonic hedgehog pathway by vismodegib represents a new therapeutic strategy.
      Adnexal carcinomas are rare malignant skin tumours derived from epithelial
      annexes. Conventional treatment of adnexal tumours is based on surgical excision.
      Although the radiosensitivity of adnexal carcinomas has not been established,
      radiotherapy could be offered alone or in combination in locally advanced or
      inoperable disease. Chemotherapy represents a therapeutic option in the treatment
      of metastatic adnexal tumours. Currently there is no effective treatment for
      these tumours when they become metastatic or unresectable, and treatment is
      palliative. Sunitinib represents a new therapeutic strategy, with efficiency
      described in the literature for a small number of patients. However, its efficacy
      is partial, and its tolerance is not always good. We report a patient with
      trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated
      effectively with vismodegib. The remarkable response we have observed in this
      patient suggests an encouraging therapeutic role of vismodegib in trichoblastic
      carcinoma that should be evaluated in a carefully designed trial. 

PMID- 25998866
TI  - Ultraviolet C radiation influences the robustness of RNA integrity measurement.
AB  - The analytical and clinical validity of analyses of RNA samples destined for
      clinical diagnosis and therapeutic management is directly impacted by RNA
      quality. RNA is affected by heat, enzymatic degradation, and Ultraviolet (UV)
      light. RNA from three eukaryotic cell lines was degraded by heat, RNase, or UV
      light. RNA integrity values obtained with the benchmark Agilent Bioanalyzer 2100
      system were compared with those from the more recent QIAxcel Advanced system. The
      application of this novel method has allowed us to unravel differences between
      RNA biophysical and biochemical degradation modes. Agilent RNA integrity number
      (RIN) and QIAxcel RIS were comparable in heat-degraded and RNase III-degraded
      RNA. Agilent RIN and QIAxcel RIS were comparable at a RIN decision level of 7 in
      UV-degraded RNA but not overall. The QIAxcel RIS method was more precise than
      Agilent RIN for RIN<8, while the inverse was true for RIN>=8. Greater degradation
      of mRNA and rRNA in UV-damaged samples hampered the Agilent RIN calculation
      algorithm. Overall, RIS was more robust than RIN for assessing RNA integrity. The
      DeltaDeltaCt-values for heat- and UV-degraded RNA samples showed slightly higher
      correlation with RIS than with RIN. RNA integrity can be used to categorize RNA
      samples for suitability for downstream gene expression analyses, independently of
      the RNA degradation mechanism. The new method QIAxcel is more robust and
      therefore allows more accurate categorization of compromised RNA samples. 

PMID- 25998867
TI  - The mediating role of secrecy in the development of psychopathology in sexually
      abused children.
AB  - Although child sexual abuse (CSA) is associated with psychopathology, limited
      research examined mechanisms through which CSA leads to psychopathology in
      children. It is generally assumed that CSA is associated with secrecy among
      children, to our knowledge this assumption has not yet been empirically tested.
      This gap in our understanding of the aftermath of CSA is surprising in light of
      abundant evidence linking secrecy to psychopathology among children. The current
      study examined whether, as compared to children who have not experienced CSA, CSA
      victims have a greater tendency for secrecy as reported by mothers and children,
      and whether psychopathology in CSA victims may be explained by their tendency to
      keep secrets. Sixty-three non-offending mothers and their sexually abused
      children (68.3% female; M age=10.89) and 48 mothers and their non-abused children
      (62.5% female; M age=11.17) completed questionnaires on secrecy and
      psychopathology (i.e., internalizing and externalizing behavior problems).
      Mothers of abused children perceived higher levels of secrecy and psychopathology
      in their children as compared to mothers of non-abused children. There were no
      differences in child-reported secrecy between abused and non-abused children.
      Mediation analyses revealed that mother-reported secrecy mediated the association
      between CSA and psychopathology. These findings suggest that secrecy is a
      potential mechanism underlying psychopathology associated with CSA, which has
      important implications for treatment of abused children. 

PMID- 25998868
TI  - A highly active and durable Co-N-C electrocatalyst synthesized using exfoliated
      graphitic carbon nitride nanosheets.
AB  - Exfoliated graphitic carbon nitride nanosheets (g-C3N4-NS) were applied for the
      first time for the preparation of an electrocatalyst for the oxygen reduction
      reaction (ORR). A less dense structure with increased surface area was observed
      for g-C3N4-NS compared to bulk g-C3N4 from detailed analyses including TEM, STEM,
      AFM with depth profiling, XRD, and UV-Vis spectroscopy. The pyrolysis of the
      prepared g-C3N4-NS with Co and carbon under an inert environment provided an
      enhanced accessibility to the N functionalities required for efficient
      interaction of Co and C with N for the formation of Co-N-C networks and produced
      a hollow and interconnected Co-N-C-NS structure responsible for high durability.
      The Co-N-C-NS electrocatalyst exhibited superior catalytic activity and
      durability and further displayed fast and selective four electron transfer
      kinetics for the ORR, as evidenced by various electrochemical experiments. The
      hollow, interconnected structure of Co-N-C-NS with increased pyridinic and
      graphitic N species has been proposed to play a key role in facilitating the
      desired ORR reaction. 

PMID- 25998863
TI  - Insulin resistance in clinical and experimental alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide;
      its management costs billions of healthcare dollars annually. Since the advent of
      the obesity epidemic, insulin resistance (IR) and diabetes have become common
      clinical findings in patients with ALD; and the development of IR predicts the
      progression from simple steatosis to cirrhosis in ALD patients. Both clinical and
      experimental data implicate the impairment of several mediators of insulin
      signaling in ALD, and experimental data suggest that insulin-sensitizing
      therapies improve liver histology. This review explores the contribution of
      impaired insulin signaling in ALD and summarizes the current understanding of the
      synergistic relationship between alcohol and nutrient excess in promoting hepatic
      inflammation and disease. 

PMID- 25998869
TI  - The research capacity of midwives.

PMID- 25998870
TI  - Exposure to violence among women with unwanted pregnancies and the association
      with post-traumatic stress disorder, symptoms of anxiety and depression.
AB  - AIM: The objective was to examine lifetime exposure to violence, physical and
      sexual, among women seeking termination of pregnancy (TOP) and its association
      with socio-demographic factors, PTSD, symptoms of anxiety and depression. DESIGN:
      The design of the study was a Swedish multi-centre study targeting women
      requesting TOP. METHODS: All women requesting TOP with a gestational length less
      than 12 pregnancy weeks were approached for participation in the study. The
      questionnaire comprised the following research instruments: Screen Questionnaire
      Post traumatic Stress Disorder (SQ-PTSD) and Hospital Anxiety and Depression
      Scale (HADS). The response rate was 57% and the final sample was 1514 women.
      Descriptive and analytic statistics were applied. RESULTS: Lifetime exposure to
      violence was common among women seeking abortion. Exposure to violence was
      associated with low education, single marital status, smoking and high alcohol
      consumption. Exposure to violence was associated with the occurrence of signs of
      PTSD and symptoms of anxiety and depression. Among those having PTSD, all had
      been exposed to sexual violence and almost all had been exposed to physical
      violence, while for those with symptoms of anxiety and depression almost half had
      been exposed to either physical or sexual violence. CONCLUSION: Exposure to
      physical and sexual abuse was common among women requesting TOP, and was strongly
      associated with the occurrence of PTSD, symptoms of anxiety and depression. This
      underscores the importance for health professionals to recognize and offer
      support to those women exposed to violence.

PMID- 25998871
TI  - Women's attitudes towards fertility and childbearing - A study based on a
      national sample of Swedish women validating the Attitudes to Fertility and
      Childbearing Scale (AFCS).
AB  - OBJECTIVE: A delay in childbearing has been reported in high-resource countries.
      Factors reported to impact postponement include being mature enough, completing
      studies, and receiving a good salary. Other reasons are the partner relationship,
      efficient forms of contraception, value changes, housing conditions, and economic
      uncertainty. The aim of the study was to validate the previously developed
      instrument Attitudes to Fertility and Childbearing Scale (AFCS) in a sample of
      Swedish women and to relate the components to the women's socio-demographic
      characteristics. METHODS: Four hundred and twenty-four women, 20-30 years of age,
      who were not mothers answered and returned the questionnaire. Statistical
      analysis was conducted; construct validity using principal component analysis
      (PCA), Student's t-test, and ANOVA was performed between the three components and
      women's background characteristics. RESULTS: The two components with highest
      loadings were Importance for future and Hindrance at present, indicating a time
      conflict. The third component was Female identity. The youngest women, single
      women, students, and women living in large cities were more likely to score high
      with the component Hindrance at present. Women having a partner were more likely
      to score high on Importance for future and Female identity. CONCLUSION: In this
      population, age, occupation, residential area, and civil (marital) status play a
      role in the attitudes towards fertility and childbearing. Fertility in relation
      to individual differences and age needs to be informed and discussed in society
      as well as in sexual and reproductive health care.

PMID- 25998872
TI  - "To be taken seriously" : women's reflections on how migration and resettlement
      experiences influence their healthcare needs during childbearing in Sweden.
AB  - OBJECTIVE: To use an intersectional approach to analyze women's reflections on
      how their migration and resettlement experiences to Sweden influenced their
      health and healthcare needs during childbearing. METHODS: Focus-group
      discussions, pair interviews and individual interviews were conducted in southern
      Sweden between 2006 and 2009, with 25 women originating from 17 different
      countries with heterogeneous backgrounds that had experienced childbirth in
      Sweden. Qualitative content analysis was used with an intersectional approach,
      taking into consideration intersections of ethnicity, socio-economic status (SES)
      and gender. FINDINGS: The hardships of migration, resettlement, and constraints
      in the daily life made the women feel overstrained, tense, and disembodied. Being
      treated as a stranger and ignored or rejected in healthcare encounters was
      devaluing and discriminating. The women stressed that they felt stronger and had
      fewer complications during pregnancy and labor when they were "taken seriously"
      and felt that they had a confident, caring relationship with caregivers/midwives.
      This, therefore, enabled the women to boost their sense of self, and to recognize
      their capabilities, as well as their "embodied knowledge". CONCLUSION:
      Caregivers/midwives should be aware of the hardships the women face. Hardships
      stem from experiences of migration and resettlement as well as from structural
      constraints such as the "triple jeopardy" of ethnicity, SES and gender, which
      increase women's needs of support in childbearing. Such awareness is necessary
      when promoting health and reducing the unnecessary suffering and victimization of
      women, their children, and their families. It is a matter of patient safety and
      equity.

PMID- 25998873
TI  - Which role do midwives and gynecologists have in smoking cessation in pregnant
      women? - A study in Flanders, Belgium.
AB  - OBJECTIVES: The objectives of our study were (1) to explore knowledge, beliefs
      and practice among midwives and gynecologists concerning a smoking cessation
      policy for pregnant women and their partners and (2) to examine if midwives and
      gynecologists do have a role in smoking cessation in pregnant women. METHOD: We
      performed a qualitative study using semi-structured interviews with nine midwives
      and eight gynecologists. Data were analyzed using deductive content analysis,
      based on the 5 A's framework (Ask-Advise-Assess-Assist-Arrange). RESULTS: The
      national smoking cessation policy seemed to be insufficiently known. "Ask" and
      "Advise" were part of a standard prenatal consultation, the next three steps were
      rarely implemented. Participants had a negative image of "the smoking pregnant
      woman": a low educated woman with a smoking partner and "bad examples" in their
      history. Reported barriers were fear of provoking resistance and lack of time and
      communication skills regarding smoking cessation. CONCLUSIONS: These findings
      suggest that training in communication skills and dealing with resistance should
      be offered, i.e. by using motivational interviewing. It could be considered that
      a trained midwife or tobaccologist is part of an obstetrical team or that the AAR
      method (Ask-Advise-Refer) is used instead of the 5 A's framework.

PMID- 25998874
TI  - Women's preferences and received pain relief in childbirth - A prospective
      longitudinal study in a northern region of Sweden.
AB  - BACKGROUND: A range of alternatives in pain management during childbirth are
      available in the western countries. Women's preferences for and use of pain
      relief methods during labour is not fully investigated. The aim of this study was
      to describe what pain relief methods pregnant women preferred when asked in late
      pregnancy and to identify factors associated with preferred and received pain
      relief methods. METHODS: A prospective longitudinal study in a northern region of
      Sweden (n = 936). Data were collected by three questionnaires. Odds ratios with a
      95% confidence interval were calculated between preferred and received pain
      relief methods for several explanatory variables. FINDINGS: The most preferred
      pain relief methods were also the most common received pain relief methods;
      nitrous oxide, bathing, breathing techniques, epidural analgesia and massage. The
      strongest factors for using different pain relief methods were primiparity and
      preferences. Women who used epidural analgesia, regardless of preference, were
      two to four times more likely to have a less positive birth experience.
      CONCLUSIONS: Women's preferences for a certain pain relief method were largely
      met. Greater differences were seen between background factors and preferences
      than the received pain relief methods. Preferences and primiparity were the most
      important factors for actually using pain relief. Epidural analgesia was
      associated with a less positive birth experience.

PMID- 25998875
TI  - First time mothers' experiences of breastfeeding their newborn.
AB  - OBJECTIVE: Despite efforts to improve continued breastfeeding, the percentages of
      exclusively breastfeeding remain low. To help the breastfeeding mother and
      reshape professional practice, we need more knowledge of maternal experiences of
      breastfeeding in the first months. The objective was to explore mothers' early
      breastfeeding experiences. METHOD: Qualitative content analysis was used to
      analyse data from 108 Danish first time mothers who had answered an open-ended
      question 6 months after birth. RESULTS: All the mothers started breastfeeding. We
      identified three overlapping phases presented as dominant themes: (1) on shaky
      ground, characterised by breastfeeding interwoven with mothering, painful
      breastfeeding, and conflicting advice, (2) searching for a foothold,
      characterised by reading the baby's cues, concerns about milk production, for or
      against breastfeeding, and looking for professional support, and (3) at ease with
      choice of feeding, characterised by a thriving baby, trust in breastfeeding
      capability, and approval of feeding preference. Together these themes and
      subthemes constituted the overall theme: being on a breastfeeding-bonding
      trajectory. CONCLUSION: Supporting the new breastfeeding mother should include
      facilitation of the transition to motherhood, learning to read the baby's cues,
      developing a sense of the right attachment at the breast, and building up the
      mother's confidence in her capability to care for the baby and produce a
      sufficient milk supply.

PMID- 25998876
TI  - "Forty is the new twenty": An analysis of British media portrayals of older
      mothers.
AB  - OBJECTIVES: Despite increased risks of infertility and poor outcomes, women in
      high-income countries are increasingly deferring pregnancy beyond age 35.The
      underlying causes are incompletely understood. The mass media is recognised as a
      powerful influence on health-related behaviour; therefore media representations
      warrant critical examination. STUDY DESIGN: Qualitative thematic analysis of
      portrayals of pregnancy and birth in women over 35 in UK national newspapers,
      popular magazines and television programmes RESULTS: Extensive media interest in
      childbearing and a preponderance of coverage related to celebrities was
      confirmed. Three main themes were identified; delayed childbearing was portrayed
      positively, as part of a life plan allowing women have the "best of both worlds".
      The media did not acknowledge age per se as an obstacle to pregnancy and endorsed
      reproductive technologies suggesting 'it's never too late'. Images and
      descriptions of ideal post-pregnancy bodies in women over 35 reinforced the
      message that "you can regain your beautiful body". CONCLUSION: Delayed
      childbearing was represented positively, as it facilitated conformity with
      dominant ideologies surrounding motherhood. Within these boundaries, the effects
      of age were disregarded. This study provides evidence of restrictive framing of
      the issues surrounding delayed childbearing in the UK media which militate
      against communication of important public health messages.

PMID- 25998877
TI  - Postpartum depression among first-time mothers - results from a parallel
      randomised trial.
AB  - OBJECTIVES: To compare the risk of postpartum depression among nulliparous women
      enrolled in a structured antenatal programme, with nulliparous women allocated to
      standard care as well as to identify obstetric characteristics in women at risk
      of developing postpartum depression. METHOD: A randomised controlled trial
      involving 1193 Danish nulliparous women. A total of 603 women attended the "Ready
      for Child program" and 590 received standard care. Data were collected from the
      ongoing local birth cohort at Aarhus University Hospital and from questionnaires
      mailed to the women attending the study. RESULTS: No difference in postpartum
      depression was found between those who attended the intervention group and the
      reference group. Overall, being at risk of postpartum depression was associated
      with preterm birth, unscheduled caesarean section, low Apgar score, lack of pain
      relief during labour, experienced low attendance of the midwife in the delivery
      room, unprepared for hospital discharge, none or minor breastfeeding in the early
      postpartum period, insufficient knowledge about breastfeeding, poor or fair self
      rated mental health, and uncertain or weak attachment to the newborn child.
      CONCLUSION: The findings suggest that a short general antenatal programme in
      pregnancy may not be sufficient to prevent postpartum depression six weeks after
      birth. However, there are several risk factors during the birth process and the
      early postpartum period that can help identify women at risk for developing
      depression.

PMID- 25998878
TI  - Health-related quality of life five years after birth of the first child.
AB  - OBJECTIVES: The aim of this study was to describe the overall health-related
      quality of life (HRQoL) in women five years after the birth of their first child
      as well as the HRQoL in relation to mode of delivery. METHODS: 545 first-time
      pregnant women, drawn from a hospital situated in Sweden, consented to be
      included in a cohort. Five years after the birth of the first child, 372 (68%)
      women agreed to participate in a follow-up study. HRQoL was measured using the
      Swedish Health-Related Quality of Life Survey (SWED-QUAL) questionnaire. Socio
      demographic background and variables related to pregnancy and childbirth were
      collected using a self-report questionnaire. RESULTS: Overall, the HRQoL was
      perceived to be good. Suboptimal scores were obtained for the three variables:
      Sleeping problems, Emotional well-being - negative affect and Family functioning 
      sexual functioning. Women having a vaginal birth, an instrumental vaginal birth
      or women who underwent caesarean section on maternal request were more likely to
      report better perceived HRQoL than women who had undergone an emergency caesarean
      section or caesarean section due to medical indication. CONCLUSION: This study
      demonstrates that the overall HRQoL of the women in the cohort was reported as
      good. Mode of delivery was associated with differences in HRQoL five years after
      birth of the first child. Our result suggests that some differences in perceived
      HRQoL persist in the long term.

PMID- 25998879
TI  - The continuing antenatal management program (CAMP): Outpatient monitoring of high
      risk pregnancies. Keeps patients safe, costs low and care nearby.
AB  - A program was developed for referred, stable, high-risk obstetrical patients
      allowing them to receive antenatal care close to a tertiary hospital without the
      costs of a hospital admission. There were 426 women managed from September 2007
      through December of 2012 with diagnosis of preterm labor, fetal anomalies,
      hypertensive disorders, placental abruption and other conditions. This management
      saved the hospital almost $9,000,000 USD or $20,956 USD per patient. 

PMID- 25998880
TI  - Pregnancy intention, receipt of pre-conception care, and pre-conception weight
      counseling reported by overweight and obese women in late pregnancy.
AB  - We surveyed overweight or obese women receiving prenatal care for a singleton
      pregnancy at a large academic medical center in 2010. During late pregnancy,
      women reported pregnancy intentionality and pre-conception weight counseling.
      Participants (N = 82) had a mean age of 29.7 (SD: 6.3) years, 61% were non
      Hispanic white, 47% were nulliparous. Before pregnancy, 45% were overweight and
      55% were obese. Forty-eight percent reported that the current pregnancy was
      planned. Of these women, 36% reported a pre-conception visit. Of these, 29%
      reported pre-conception weight counseling (5% of sample). Unrealized
      opportunities exist in the clinical setting for promoting weight management
      during the childbearing years. 

PMID- 25998881
TI  - Two years after Newtown--public opinion on gun policy revisited.

PMID- 25998882
TI  - Guest Commentary: Fat and other taxes, lessons for the implementation of
      preventive policies.
AB  - Fat, sugar or sweetened beverage taxes are part of an overall public health
      nutrition approach to healthy eating. They are not approaches that on their own
      are likely to bring about change. Policy evidence from existing food tax
      implementation suggest that taxes need to be paralleled by subsidies and other
      interventions to encourage healthy eating. Such dual methods help not only
      contribute to nutrition outcomes but also ensure political support for food
      taxes. Politicians and policy makers are suspicious of taxes, using subsidies and
      revenue monies from taxes to support healthy eating is more likely to encourage
      both political and public support. Building support for policies is never just a
      matter of academic evidence. Public health advocates need to show more ambition
      by developing skills in implementing pricing policies to support healthy eating.
      Key opponents to taxes are the food industry who use a range of arguments to
      prevent taxation being implemented. Public health advocates are weak in tackling
      the issues of corporate power and providing evidence to maintain policy and
      political support. The public health movement needs to continue to develop the
      political will among politicians and the public for taxes on food. A new way of
      looking at policy formation is required and this includes addressing the power of
      corporate interests and the role of professionals in shaping or combating these
      influences. 

PMID- 25998883
TI  - Critical Role of TAK1-Dependent Nuclear Factor-kappaB Signaling in 2,3,7,8
      Tetrachlorodibenzo-p-dioxin-induced Astrocyte Activation and Subsequent Neuronal
      Death.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been recently shown to elicit
      inflammatory response in a number of cell-types. However, whether TCDD could
      provoke inflammation in astrocytes, the most abundant glial cells in central
      nervous system (CNS), remains virtually unknown. In the present study, we showed
      that TCDD exposure could induce evident astrocyte activation both in vivo and in
      vitro. Further, we found that TGF-beta-activated kinase 1 (TAK1), a critical
      regulator of NF-kappaB signaling, was rapidly phosphorylated in the process of
      TCDD-induced reactive astroglia. Exposure to TCDD led to rapid TAK1 and NF-kappaB
      p65 phosphorylation, as well as IKBalpha degradation. Moreover, blockage of TAK1
      using siRNA oligos or TAK1 inhibitor 5Z-7-oxozeaenol significantly attenuated
      TCDD-induced astrocyte activation as well as the release of TNF-alpha. Finally,
      we showed that the conditioned medium of TCDD-treated astrocytes promoted the
      apoptosis of PC12 neuronal cells, which could be blocked with the pre-treatment
      of TAK1 inhibitor. Taken together, these findings suggested that TCDD could
      promote the inflammatory activation of astrocytes through modulating TAK1-NF
      kappaB cascade, implicating that reactive astrocytes might contribute to TCDD
      induced adverse effects on CNS system.

PMID- 25998884
TI  - Malate-Aspartate Shuttle Inhibitor Aminooxyacetate Acid Induces Apoptosis and
      Impairs Energy Metabolism of Both Resting Microglia and LPS-Activated Microglia.
AB  - NADH shuttles mediate the transfer of the reducing equivalents of 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
      such biological processes as glutamate synthesis in neurons. However, there has
      been no information regarding the roles of NADH shuttle in the survival and
      energy metabolism of microglia. In current study, using microglial BV2 cells as a
      cellular model, we determined the roles of MAS in the survival and energy
      metabolism of microglia by using aminooxyacetate acid (AOAA)-a widely used MAS
      inhibitor. Our study has suggested that AOAA can effectively inhibit the MAS
      activity of the cells. We also found that AOAA can induce both early- and late
      stage apoptosis of resting microglia and lipopolysaccharides (LPS)-activated
      microglia. AOAA also induced mitochondrial depolarization, increases in the
      cytosolic Ca(2+) concentrations, and decreases in the intracellular ATP levels.
      Moreover, our study has excluded the possibility that the major nonspecific
      effect of AOAA-inhibition of GABA transaminase-is involved in theses effects of
      AOAA. Collectively, our study has provided first information suggesting
      significant roles of MAS in the survival and energy metabolism in both resting
      microglia and LPS-activated microglia. 

PMID- 25998885
TI  - Administration of SB203580, a p38 MAPK Inhibitor, Reduced the Expression of MMP9,
      and Relieved Neurologic Severity in the Experimental Autoimmune Neuritis (EAN) in
      Rats.
AB  - Dysfunctional expression of matrix metalloproteinase-9 (MMP-9) has been found to
      be closely associated with the experimental autoimmune neuritis (EAN). In this
      study, we explored the role of p38 mitogen-activated protein kinases (p38 MAPK)
      in the regulation of MMP-9 in sciatic nerves of EAN rats. We analyzed the
      expression changes of MMP-2, MMP-3, MMP-9, and mitogen-activated protein kinases
      (MAP kinases) in sciatic nerves of EAN rats and investigated the effect of p38
      MAPK inhibitor (SB203580) on MMP-9 expression and pathological changes in EAN.
      Real-time PCR and western blot analyses showed that the expression of MMP-2
      exhibited no significant changes throughout the course of EAN, while MMP-3 and
      MMP-9 presented the relatively increased expression compared with that in control
      group. MAP kinases, including p38 MAPK, ERK1/2, and JNK1/2, were activated in the
      sciatic nerve of EAN rats, and phosphorylated p38 MAPK showed similar patterns of
      expression to MMP-9. The expression of MMP-9 and phosphorylated p38 MAPK in
      sciatic nerves were in positive correlation with disease severity. In addition,
      SB203580 treatment significantly reduced the mRNA and protein level of MMP-9 in
      sciatic nerves on the peak phase of EAN. Inhibition of p38 MAPK also relieved
      neurologic severity and ameliorated pathological changes in EAN. In conclusion,
      SB203580 may ameliorate clinical deficit and pathological changes in EAN by
      reducing the MMP-9 expression in sciatic nerves, which suggest that p38 MAPK
      inhibitor such as SB203580 could be considered as a therapeutic candidate in
      autoimmune neuropathies. 

PMID- 25998886
TI  - Preventive Effect of Cecropia pachystachya Against Ketamine-Induced Manic
      Behavior and Oxidative Stress in Rats.
AB  - Cecropia species are widely used in traditional medicine by its anti-diabetic,
      anti-hypertensive and anti-inflammatory properties. In the present study, we
      investigated the neuroprotective and antioxidant effects of the crude aqueous
      extract from Cecropia pachystachya leaves in a rat model of mania induced by
      ketamine. The results indicated that ketamine treatment (25 mg/kg i.p., for 8
      days) induced hyperlocomotion in the open-field test and oxidative damage in
      prefrontal cortex and hippocampus, evaluated by increased lipid peroxidation,
      carbonyl protein formation and decreased total thiol content. Moreover, ketamine
      treatment reduced the activity of the antioxidant enzymes superoxide dismutase
      and catalase in hippocampus. Pretreatment of rats with C. pachystachya aqueous
      extract (200 and 400 mg/kg p.o., for 14 days) or with lithium chloride (45 mg/kg
      p.o., for 14 days, used as a positive control) prevented both behavioral and pro
      oxidant effects of ketamine. These findings suggest that C. pachystachya might be
      a useful tool for preventive intervention in bipolar disorder, reducing the
      episode relapse and the oxidative damage associated with the manic phase of this
      disorder . 

PMID- 25998887
TI  - Nodakenin Enhances Cognitive Function and Adult Hippocampal Neurogenesis in Mice.
AB  - In our previous study, we demonstrated that nodakenin, a coumarin compound
      isolated from Angelica decursiva, ameliorates learning and memory impairments
      induced by scopolamine. In the present study, we investigated the effects of
      nodakenin on the cognitive function in the normal naive mice in a passive
      avoidance task, and the results showed that nodakenin significantly increased the
      latency time in normal naive mice. In addition, sub-chronic administration of
      nodakenin increased the number of 5-bromo-2-deoxyuridine (BrdU)-positive cells in
      the hippocampal dentate gyrus (DG) region. The percentage of BrdU and NeuN
      (neuronal cell marker)-immunopositive cells was also significantly increased by
      the nodakenin administration. Western blotting results showed that the expression
      levels of phosphorylated protein kinase B (Akt) and phosphorylated glycogen
      synthase kinase-3beta (GSK-3beta) were significantly increased in hippocampal
      tissue by sub-chronic nodakenin administration. These findings suggest that the
      sub-chronic administration of nodakenin enhances adult hippocampal neurogenesis
      in the DG region via Akt-GSK-3beta signaling and this increase may be associated
      with nodakenin's positive effect on cognitive processing. 

PMID- 25998889
TI  - Angiotensin-Converting Enzyme 2 Attenuates Bleomycin-Induced Lung Fibrosis in
      Mice.
AB  - BACKGROUND: Local renin-angiotensin system (RAS) activation has been shown to
      play an important role in the pathogenesis of idiopathic pulmonary fibrosis
      (IPF). It has been reported that angiotensin-converting enzyme 2 (ACE2) could
      inhibit RAS-mediated epithelial injury and fibrogenesis and that ACE2 deficiency
      could aggravate acute and chronic lung injury. Through research, it could be
      deduced that ACE2 could protect against pulmonary fibrosis as a therapeutic
      target. METHODS: Time-course analysis of the pathological characteristics of
      bleomycin-induced lung fibrosis was undertaken in a mouse model, and the effect
      of exogenous ACE2 on lung fibrosis was studied. Immunohistchemistry (IHC)
      staining and western blot (WB) testing for AGT and ACE2 were performed to
      evaluate the regulation of local RAS. TUNEL staining was used to observe
      epithelial apoptosis. Leukocyte common antigen (LCA) and pulmonary surfactant
      associated protein A (SP-A) IHC staining and WB testing were performed to assess
      the inflammatory response and epithelial regeneration. Masson's staining and a
      hydroxyproline assay were performed to examine collagen deposition. IHC staining
      and WB testing for TGF-beta1 and alpha-SMA were performed to investigate the
      regulation of pro-fibrotic cytokines and the activation of fibroblasts. RESULTS:
      Exogenous ACE2 attenuated bleomycin-induced lung fibrosis by reversing the
      reduction of local ACE2 and by suppressing the elevation of AGT. ACE2 decreased
      the apoptosis index and LCA levels and ameliorated the dynamic change in SP-A
      level, thus protecting against epithelial injury. Reductions of TGF-beta1 and
      alpha-SMA were also found in ACE2-treated mice, indicating the inhibition of
      fibrogenesis. CONCLUSION: ACE2 attenuated bleomycin-induced lung fibrosis as an
      anti-inflammatory anti-apoptotic and anti-fibrotic agent, and it might be a
      promising therapeutic target for IPF.

PMID- 25998888
TI  - Melatonin Protects Methamphetamine-Induced Neuroinflammation Through NF-kappaB
      and Nrf2 Pathways in Glioma Cell Line.
AB  - Methamphetamine (METH) is known as a toxin for neuronal and glial cells. Previous
      studies have found that METH-induced glial cell death and inflammation is
      mediated by oxidative stress. However, the exact mechanisms of the inflammatory
      response remain unclear. Therefore, we hypothesized that the activation of
      nuclear factor-kappaB (NF-kappaB) signaling, a key mediator of inflammation, and
      the inhibition of nuclear factor erythroid 2-related factor-2 (Nrf2) signaling, a
      regulator of the antioxidant response, would be significant events occurring in
      response to METH-induced inflammation in a rat glioma cell line (C6 cells). Our
      results show that METH increased the production of nitric oxide (NO) and up
      regulated the expression of its main regulatory protein, inducible nitric oxide
      synthase (iNOS). METH also induced NF-kappaB activation by increasing inhibitory
      kappaBalpha (IkappaBalpha) degradation and translocation of the NF-kappaB (p65)
      subunit into the nucleus. Additionally, METH inhibited the activation of the Nrf2
      pathway by decreasing the translocation of Nrf2 into the nucleus and also by
      suppressing the expression of heme oxygenase-1 (HO-1), NAD(P)H quinone
      oxidoreductase-1 (NQO-1), and glutamate-cysteine ligase catalytic subunit (gamma
      GCLC), resulting in the suppression of superoxide dismutase (SOD) activity.
      Pretreatment with melatonin effectively promoted Nrf2 activation and reversed the
      METH-induced NF-kappaB response. Melatonin increased the expression of HO-1, NQO
      1, and gamma-GCLC, resulting in increased SOD activity. In addition, melatonin
      also decreased IkappaBalpha degradation, translocation of the p65 subunit, and
      expression of iNOS, resulting in decreased NO production. Taken together, our
      results indicate that melatonin diminishes the proinflammatory mediator in METH
      stimulated C6 cells by inhibiting NF-kappaB activation and inducing Nrf2-mediated
      HO-1, NQO-1, and gamma-GCLC expression. 

PMID- 25998890
TI  - Comparison of Everolimus- versus Sirolimus-eluting stents in the provisional
      Bifurcation stenting guided by intravascular ultrasound: mid-term results of the
      J-REVERSE registry.
AB  - This study aimed at comparing the mid-term clinical outcome of everolimus-eluting
      (EES) with sirolimus-eluting (SES) stents in the provisional bifurcation stenting
      guided by intravascular ultrasound (IVUS). We compared the clinical outcome up to
      9-month follow-up results of the prospective J-REVERSE registry of 300 non-left
      main bifurcation lesions in 298 patients treated with EES (n = 240) and SES (n =
      60). The SB dilation with the kissing balloon technique (KBT) was performed in 54
      %. The patient and lesion characteristics of the groups were similar. The
      incidences of SB dissections, occlusions, stenting, and slow flow were similar. A
      greater luminal volume gain was achieved in the proximal MV after KBT compared in
      non-KBT treated lesions in the EES group (7.9 +/- 2.4 versus 7.0 +/- 2.0
      mm(3)/mm, p = 0.002), though not in the SES group. The SB diameter stenosis in
      the non-KBT treatment at 9 months was greater than the KBT in both groups. The
      incidence of target lesion revascularisation (TLR) was 5.0 % in the EES versus
      8.3 % in the SES group (p = 0.35), and the incidence of major adverse cardiac
      events, including TLR, myocardial infarction, stent thrombosis, and death was 5.4
      % in the EES versus 11.7 % in the SES group (p = 0.15). IVUS-guided provisional
      stenting with EES achieved a greater luminal gain after than without KBT, and
      similar clinical outcomes as with SES up to 9-month follow-up.

PMID- 25998891
TI  - A case of coronary rupture and pseudoaneurysm formation after fracture of
      implanted paclitaxel-eluting stents.
AB  - A 48-year-old man who had undergone implantation of two paclitaxel-eluting stents
      (PESs) at the right coronary artery was admitted to our hospital with progressive
      dyspnea. In the coronary care unit, he developed cardiogenic shock due to cardiac
      tamponade treated by pericardiocentesis. A coronary angiogram showed a large
      pseudoaneurysm at the site of the previously implanted stents, suggesting
      coronary rupture due to implanted stent fracture. The pseudoaneurysm was
      completely sealed by polytetrafluoroethylene-covered stent implantation. Although
      this case is very rare, coronary rupture by stent fracture should be considered
      when cardiac tamponade occurs after drug-eluting stent implantation, especially
      PES. 

PMID- 25998892
TI  - beta-Blocker Use and Risk of Recurrence in Patients with Early Breast Cancer.
AB  - AIM: We evaluated whether the concurrent beta-blocker use in early breast cancer
      patients influenced the outcome in terms of preventing tumor recurrence after
      adjuvant chemotherapy. METHODS: We retrospectively reviewed the medical records
      of 610 patients with breast cancer. Thereafter, we compared overall disease-free
      survival (DFS) between beta-blocker users and nonusers. RESULTS: Those not
      receiving beta-blockers had a relatively longer mean DFS (10.8 vs. 9.7 years),
      although the difference did not reach statistical significance (p = 0.651). When
      the survival analysis was adjusted for age, tumor stage, hormone receptor status
      and HER2 status, the results remained unaltered, suggesting that beta-blocker use
      did not significantly improve overall DFS (HR, 0.849; 95% CI, 0.537-1.343; p =
      0.485). CONCLUSION: Our findings failed to confirm previous results indicating a
      potential antitumor effect of beta-blockers.

PMID- 25998895
TI  - T-peak to T-end interval for prediction of ventricular tachyarrhythmia and
      mortality in a primary prevention population with systolic cardiomyopathy.
AB  - BACKGROUND: The electrocardiographic T-wave peak to T-wave end interval (Tpe)
      correlates with dispersion of ventricular repolarization (DVR). Increased DVR
      increases propensity toward electrical reentry that can cause ventricular
      tachyarrhythmia. The baseline rate-corrected Tpe (Tpec) has been shown to predict
      ventricular tachyarrhythmia and death in multiple patient populations but not
      among cardiomyopathic patients undergoing insertion of an implantable
      cardioverter-defibrillator (ICD) for primary prevention. OBJECTIVE: The purpose
      of this study was to assess the risk stratification ability of the Tpec in
      patients with systolic cardiomyopathy without prior ventricular tachyarrhythmia
      (ie, the primary prevention population). METHODS: We performed prospective follow
      up of 305 patients (73% men; left ventricular ejection fraction [LVEF] 23 +/- 7%)
      with LVEF <=35% and an ICD implanted for primary prevention. Baseline ECGs were
      analyzed with automated algorithms. Endpoints were ventricular tachycardia
      (VT)/ventricular fibrillation (VF), death, and a combined endpoint of VT/VF or
      death, assessed by device follow-up and Social Security Death Index query.
      RESULTS: The average Tpec was 107 +/- 22 ms. During device clinic follow-up of 31
      +/- 23 months, 82 patients (27%) had appropriate ICD therapy for VT/VF, and
      during mortality follow-up of 49 +/- 21 months, 91 patients (30%) died. On
      univariable analysis, Tpec predicted VT/VF, death, and the combined endpoint of
      VT/VF or death (P < .05 for each endpoint). Multivariable analysis included
      univariable predictors among demographics, clinical data, laboratory data,
      medications used, and electrocardiography parameters. After correction, Tpec
      remained predictive of VT/VF (hazard ratio [HR] per 10-ms increase 1.16, P =
      .009), all-cause mortality (HR per 10 ms 1.13, P = .05), and the combined
      endpoint (HR per 10 ms 1.17, P = .001). CONCLUSION: Tpec independently predicts
      both VT/VF and overall mortality in patients with systolic dysfunction and ICDs
      implanted for primary prevention.

PMID- 25998896
TI  - Risk markers of sudden death on the 12-lead ECG: Tpeak-Tend interval makes the
      cut.

PMID- 25998897
TI  - Low vulnerability of the right phrenic nerve to electroporation ablation.
AB  - BACKGROUND: Circular electroporation ablation is a novel ablation modality for
      electrical pulmonary vein isolation. With a single 200-J application, deep
      circular myocardial lesions can be created. However, the acute and chronic
      effects of this energy source on phrenic nerve (PN) function are unknown.
      OBJECTIVE: The purpose of this study was to analyze nerve vulnerability to
      electroporation ablation in a porcine model. METHODS: In 20 animals (60-75 kg),
      the course of the right PN was pace-mapped inside the superior caval vein (SCV).
      Thereafter, a single 200-J circular electroporation ablation was performed via a
      multipolar circular catheter in firm contact with the inner SCV wall. RESULTS: In
      19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory
      above the right atrial contour. Directly after the application, the PN could be
      captured above the ablation level in 17 of 19 animals and after maximally 30
      minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN
      functionality was unaffected in all. Histological analysis in 5 animals in which
      the application had been delivered in the muscular sleeve just above the right
      atrium showed a transmural circular lesion. However, no lesion was found in the
      other animals in which the application had been delivered in the fibrous section
      more cranial in the SCV. CONCLUSIONS: Electroporation ablation at an energy level
      that may create deep myocardial lesions may spare the targeted right PN. These
      animal data suggest that electroporation may be a safe ablation modality near the
      right PN.

PMID- 25998898
TI  - Diagnostic Errors that Lead to Inappropriate Antimicrobial Use.
AB  - OBJECTIVE: We found previously that inappropriate inpatient antimicrobial use was
      often attributable to erroneous diagnoses. Here, we detail diagnostic errors and
      their relationship to inappropriate antimicrobial courses. DESIGN: Retrospective
      cohort study. SETTING: Veterans Affairs hospital. PATIENTS: A cohort of 500
      randomly selected inpatients with an antimicrobial course. METHODS: Blinded
      reviewers judged the accuracy of the initial provider diagnosis for the condition
      that led to an antimicrobial course and whether the course was appropriate.
      RESULTS The diagnoses were correct in 291 cases (58%), incorrect in 156 cases
      (31%), and of indeterminate accuracy in 22 cases (4%). In the remaining 31 cases
      (6%), the diagnosis was a sign or symptom rather than a syndrome or disease. The
      odds ratio of a correct diagnosis was 4.3 (95% confidence interval [CI], 2.2-8.5)
      if the index condition was related to the reason for admission. When the
      diagnosis was correct, 181 of 292 courses (62%) were appropriate, compared with
      only 10 of 208 (5%) when the diagnosis was incorrect or indeterminate or when
      providers were treating a sign or symptom rather than a syndrome or disease
      (P<.001). Among the 309 cases in which antimicrobial courses were not
      appropriate, reasons varied by diagnostic accuracy; in 81 of 111 cases (73%) with
      a correct diagnosis, incorrect antimicrobial(s) were selected; in 166 of 198
      other cases (84%), antimicrobial therapy was not indicated. CONCLUSIONS:
      Diagnostic accuracy is important for optimal inpatient antimicrobial use.
      Antimicrobial stewardship strategies should help providers avoid diagnostic
      errors and know when antimicrobial therapy can be withheld safely.

PMID- 25998899
TI  - The ectopic expression of Snail in MDBK cells does not induce epithelial
      mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT), a key process in the tumor metastatic
      cascade, is characterized by the loss of cell-cell junctions and cell polarity,
      as well as by the acquisition of migratory and invasive properties. However, the
      precise molecular events that initiate this complex EMT process are poorly
      understood. Snail expression induces EMT in Madin-Darby canine kidney (MDCK)
      cells and the human epidermoid carcinoma cell line, A431. Snail is a zinc finger
      transcription factor and triggers EMT by suppressing E-cadherin expression. In
      the present study, to broaden our knowledge of Snail-induced EMT, we generated
      stable Snail transfectants using Madin-Darby bovine kidney (MDBK) cells. Contrary
      to the MDCK or A431 cells examined in our previous studies, the MDBK cells
      transfected with the Snail construct maintained an epithelial morphology and
      showed no sign of reduced cell-cell adhesiveness compared to the control cells.
      Consistent with these observations, the downregulation of epithelial marker
      proteins, e.g. E-cadherin and desmoglein, and the upregulation of mesenchymal
      marker proteins, e.g., N-cadherin and fibronectin, were not detected.
      Furthermore, the E-cadherin promoter was not methylated. Therefore, in the MDBK
      cells, the ectopic expression of Snail failed to induce EMT. As previously
      demonstrated, in MDCK cells, Snail expression is accompanied by the increased
      expression of other EMT-inducing transcription factors, e.g., Slug and zinc
      finger E-box-binding homeobox 1 (ZEB1). However, the MDBK cells transfected with
      the Snail construct did not exhibit an increased expression of these factors.
      Thus, it is possible that the failure to upregulate other EMT-related
      transcription factors may explain the lack of Snail-mediated induction of EMT in
      MDBK cells.

PMID- 25998902
TI  - Ectopic overexpression of the cell wall invertase gene CIN1 leads to dehydration
      avoidance in tomato.

PMID- 25998901
TI  - Postprandial glycaemic response: how is it influenced by characteristics of
      cereal products?
AB  - Cereal products exhibit a wide range of glycaemic indexes (GI), but the
      interaction of their different nutrients and starch digestibility on blood
      glucose response is not well known. The objective of this analysis was to
      evaluate how cereal product characteristics can contribute to GI and insulinaemic
      index and to the parameters describing glycaemic or insulinaemic responses
      (incremental AUC, maximum concentration and Deltapeak). Moreover, interactions
      between the different cereal products characteristics and glycaemic response
      parameters were assessed for the first time. Relationships between the cereal
      products characteristics and the glycaemic response were analysed by partial
      least square regressions, followed by modelling. A database including 190 cereal
      products tested by the usual GI methodology was used. The model on glycaemic
      responses showed that slowly digestible starch (SDS), rapidly digestible starch
      (RDS) and fat and fibres, and several interactions involving them, significantly
      explain GI by 53 % and Deltapeak of glycaemia by 60 %. Fat and fibres had
      important contributions to glycaemic response at low and medium SDS contents in
      cereal products, but this effect disappears at high SDS levels. We showed also
      for the first time that glycaemic response parameters are dependent on
      interactions between starch digestibility (interaction between SDS and RDS) and
      nutritional composition (interaction between fat and fibres) of the cereal
      products. We also demonstrated the non-linear effect of fat and fibres
      (significant effect of their quadratic terms). Hence, optimising both the formula
      and the manufacturing process of cereal products can improve glucose metabolism,
      which is recognised as strongly influential on human health. 

PMID- 25998900
TI  - Type 2 diabetes as a protein misfolding disease.
AB  - Type 2 diabetes (T2D) is a highly prevalent and chronic metabolic disorder.
      Recent evidence suggests that formation of toxic aggregates of the islet amyloid
      polypeptide (IAPP) might contribute to beta-cell dysfunction and disease.
      However, the mechanism of protein aggregation and associated toxicity remains
      unclear. Misfolding, aggregation, and accumulation of diverse proteins in various
      organs is the hallmark of the group of protein misfolding disorders (PMDs),
      including highly prevalent illnesses affecting the central nervous system (CNS)
      such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this review we
      discuss the current understanding of the mechanisms implicated in the formation
      of protein aggregates in the endocrine pancreas and associated toxicity in the
      light of the long-standing knowledge from neurodegenerative disorders associated
      with protein misfolding. 

PMID- 25998903
TI  - The Venus flytrap attracts insects by the release of volatile organic compounds.

PMID- 25998906
TI  - beta-cyclocitral upregulates salicylic acid signalling to enhance excess light
      acclimation in Arabidopsis.
AB  - beta-cyclocitral (beta-CC), a volatile oxidized derivative of beta-carotene, can
      upregulate the expression of defence genes to enhance excess light (EL)
      acclimation. However, the signalling cascades underlying this process remain
      unclear. In this study, salicylic acid (SA) is involved in alleviating damage to
      promote beta-CC-enhanced EL acclimation. In early stages of EL illumination, beta
      CC pretreatment induced SA accumulation and impeded reactive oxygen species (ROS)
      production in the chloroplast. A comparative analysis of two SA synthesis
      pathways in Arabidopsis revealed that SA concentration mainly increased via the
      isochorismate synthase 1 (ICS1)-mediated isochorismate pathway, which depended on
      essential regulative function of enhanced disease susceptibility 1 (EDS1).
      Further results showed that, in the process of beta-CC-enhanced EL acclimation,
      nuclear localization of nonexpressor of pathogenesis-related genes 1 (NPR1) was
      regulated by SA accumulation and NPR1 induced subsequent transcriptional
      reprogramming of gluthathione-S-transferase 5 (GST5) and GST13 implicated in
      detoxification. In summary, beta-CC-induced SA synthesis contributes to EL
      acclimation response by decreasing ROS production in the chloroplast, promoting
      nuclear localization of NPR1, and upregulating GST transcriptional expression.
      This process is a possible molecular regulative mechanism of beta-CC-enhanced EL
      acclimation. 

PMID- 25998904
TI  - The role of cis-zeatin-type cytokinins in plant growth regulation and mediating
      responses to environmental interactions.
AB  - Cytokinins (CKs) are well-established as important phytohormonal regulators of
      plant growth and development. An increasing number of studies have also revealed
      the function of these hormones in plant responses to biotic and abiotic stresses.
      While the function of certain CK classes, including trans-zeatin and
      isopentenyladenine-type CKs, have been studied in detail, the role of cis-zeatin
      type CKs (cZs) in plant development and in mediating environmental interactions
      is less well defined. Here we provide a comprehensive summary of the current
      knowledge about abundance, metabolism and activities of cZs in plants. We outline
      the history of their analysis and the metabolic routes comprising cZ biosynthesis
      and degradation. Further we provide an overview of changes in the pools of cZs
      during plant development and environmental interactions. We summarize studies
      that investigate the role of cZs in regulating plant development and defence
      responses to pathogen and herbivore attack and highlight their potential role as
      'novel' stress-response markers. Since the functional roles of cZs remain largely
      based on correlative data and genetic manipulations of their biosynthesis,
      inactivation and degradation are few, we suggest experimental approaches using
      transgenic plants altered in cZ levels to further uncover their roles in plant
      growth and environmental interactions and their potential for crop improvement. 

PMID- 25998905
TI  - The Arabidopsis thaliana elongator complex subunit 2 epigenetically affects root
      development.
AB  - The elongator complex subunit 2 (ELP2) protein, one subunit of an evolutionarily
      conserved histone acetyltransferase complex, has been shown to participate in
      leaf patterning, plant immune and abiotic stress responses in Arabidopsis
      thaliana. Here, its role in root development was explored. Compared to the wild
      type, the elp2 mutant exhibited an accelerated differentiation of its root stem
      cells and cell division was more active in its quiescent centre (QC). The key
      transcription factors responsible for maintaining root stem cell and QC identity,
      such as AP2 transcription factors PLT1 (PLETHORA1) and PLT2 (PLETHORA2), GRAS
      transcription factors such as SCR (SCARECROW) and SHR (SHORT ROOT) and WUSCHEL
      RELATED HOMEOBOX5 transcription factor WOX5, were all strongly down-regulated in
      the mutant. On the other hand, expression of the G2/M transition activator CYCB1
      was substantially induced in elp2. The auxin efflux transporters PIN1 and PIN2
      showed decreased protein levels and PIN1 also displayed mild polarity alterations
      in elp2, which resulted in a reduced auxin content in the root tip. Either the
      acetylation or methylation level of each of these genes differed between the
      mutant and the wild type, suggesting that the ELP2 regulation of root development
      involves the epigenetic modification of a range of transcription factors and
      other developmental regulators.

PMID- 25998907
TI  - Phosphorylation of TGB1 by protein kinase CK2 promotes barley stripe mosaic virus
      movement in monocots and dicots.
AB  - The barley stripe mosaic virus (BSMV) triple gene block 1 (TGB1) protein is
      required for virus cell-to-cell movement. However, little information is
      available about how these activities are regulated by post-translational
      modifications. In this study, we showed that the BSMV Xinjiang strain TGB1
      (XJTGB1) is phosphorylated in vivo and in vitro by protein kinase CK2 from barley
      and Nicotiana benthamiana. Liquid chromatography tandem mass spectrometry
      analysis and in vitro phosphorylation assays demonstrated that Thr-401 is the
      major phosphorylation site of the XJTGB1 protein, and suggested that a Thr-395
      kinase docking site supports Thr-401 phosphorylation. Substitution of Thr-395
      with alanine (T395A) only moderately impaired virus cell-to-cell movement and
      systemic infection. In contrast, the Thr-401 alanine (T401A) virus mutant was
      unable to systemically infect N. benthamiana but had only minor effects in
      monocot hosts. Substitution of Thr-395 or Thr-401 with aspartic acid interfered
      with monocot and dicot cell-to-cell movement and the plants failed to develop
      systemic infections. However, virus derivatives with single glutamic acid
      substitutions at Thr-395 and Thr-401 developed nearly normal systemic infections
      in the monocot hosts but were unable to infect N. benthamiana systemically, and
      none of the double mutants was able to infect dicot and monocot hosts. The mutant
      XJTGB1T395A/T401A weakened in vitro interactions between XJTGB1 and XJTGB3
      proteins but had little effect on XJTGB1 RNA-binding ability. Taken together, our
      results support a critical role of CK2 phosphorylation in the movement of BSMV in
      monocots and dicots, and provide new insights into the roles of phosphorylation
      in TGB protein functions. 

PMID- 25998908
TI  - Pemphigus vulgaris antibodies target the mitochondrial nicotinic acetylcholine
      receptors that protect keratinocytes from apoptolysis.
AB  - The mechanism of detachment and death of keratinocytes in pemphigus vulgaris (PV)
      involves pro-apoptotic action of constellations of autoantibodies determining
      disease severity and response to treatment. The presence of antibodies to
      nicotinic acetylcholine receptors (nAChRs) and the therapeutic efficacy of
      cholinomimetics in PV is well-established. Recently, adsorption of anti
      mitochondrial antibodies abolished the ability of PVIgGs to cause acantholysis,
      demonstrating their pathophysiological significance. Since, in addition to cell
      membrane, nAChRs are also present on the mitochondrial outer membrane, wherein
      they act to prevent activation of intrinsic (mitochondrial apoptosis), we
      hypothesized that mitochondrial (mt)-nAChRs might be targeted by PVIgGs. To test
      this hypothesis, we employed the immunoprecipitation-western blot assay of
      keratinocyte mitochondrial proteins that visualized the alpha3, alpha5, alpha7,
      alpha9, alpha10, beta2 and beta4 mt-nAChR subunits precipitated by PV IgGs,
      suggesting that functions of mt-nAChRs are compromised in PV. To
      pharmacologically counteract the pro-apoptotic action of anti-mitochondrial
      antibodies in PV, we exposed naked keratinocyte mitochondria to PVIgGs in the
      presence of the nicotinic agonist nicotine +/- antagonists, and measured
      cytochrome c (CytC) release. Nicotine abolished PVIgG-dependent CytC release,
      showing a dose-dependent effect, suggesting that protection of mitochondria can
      be a novel mechanism of therapeutic action of nicotinic agonists in PV. The
      obtained results indicated that the mt-nAChRs targeted by anti-mitochondrial
      antibodies produced by PV patients are coupled to inhibition of CytC release, and
      that nicotinergic stimulation can abolish PVIgG-dependent activation of intrinsic
      apoptosis in KCs. Future studies should determine if and how the distinct anti-mt
      nAChR antibodies penetrate KCs and correlate with disease severity.

PMID- 25998910
TI  - Bilateral quadriceps and triceps tendon rupture in a hemodialysis patient.
AB  - This paper presented a 58-year-old hemodialysis patient who had bilateral
      quadriceps and triceps tendon rupture, whereby the role of rehabilitation in
      functional parameters has been highlighted. 

PMID- 25998911
TI  - An organic anion template: a 24-nucleus silver cluster encapsulating a squarate
      dimer.
AB  - The first silver cluster encapsulating an organic anion-squarate dianion-has been
      synthesized. Two C4O4(2-) anions arranged in a staggered sandwich type
      arrangement are confined in the Ag24 cage. The incorporation of squarate anions
      into the silver alkynyl system leads to the red shift of absorption of the
      cluster in comparison to silver squarate. 

PMID- 25998912
TI  - The policy process for health promotion.
AB  - AIMS: The paper aims to contribute to our understanding of the policy process in
      health promotion by addressing the following questions: What are the
      characteristics of the policy process in health promotion? How do policy
      entrepreneurs influence project implementation? METHODS: This is a qualitative
      study with an explorative case study design that uses three different data
      sources: qualitative interviews, written documents and observations. RESULTS: The
      paper examines several factors (determinants) that influence the policy process
      and that, to a lesser extent, are addressed by current models in health policy
      research. Legitimacy, financial capacity, available structure and political
      timing are all important determinants that influence the policy process. Policy
      entrepreneurs, with established networks and knowledge of the environment and its
      procedures, create legitimacy and provide opportunities for action; however,
      indistinct organizational boundaries among roles and poorly defined individual
      responsibilities create policy process uncertainty. As a result, there are
      lengthy discussions and few decisions, both of which delay the progress of a
      project. CONCLUSIONS: This paper's theoretical contribution is its analysis of
      the relationship of policy-making to linear models, via a discussion of policy
      entrepreneurs, and their importance in the policy process. The paper concludes
      that we need to consider the influence of policy entrepreneurs, whom build
      legitimacy and seize action opportunities by coupling the three streams in the
      policy process, as they help bring projects to fruition. Furthermore, the study
      points to the importance of policy entrepreneurs throughout the policy process.
      The paper has practical implications for practitioners whom work with the
      implementation of community policies.

PMID- 25998913
TI  - The autoinflammatory diseases: a fashion with blurred boundaries!
AB  - Monogenic autoinflammatory diseases are defined as a group of conditions with a
      clinical and biological inflammatory syndrome but little or no evidence of
      autoimmunity. Over 17 years have passed since the discovery of the first
      autoinflammatory gene, MEFV, responsible for familial Mediterranean fever.
      Substantive progress has been made since then, highlighting the key role of the
      inflammasome in the maintenance of the cell homeostasis but also unravelling new
      pathophysiological pathways involved in these diseases. The history of
      autoinflammatory gene discovery demonstrates the powerfulness of next-generation
      sequencing approaches in linking inflammatory disorders with various overlapping
      phenotypes. It can be easily anticipated that new genes will be exponentially
      identified in the coming years. Integrating these new concepts should help to
      promote personalized patient care through novel therapeutic opportunities. 

PMID- 25998909
TI  - Environmental Basis of Autoimmunity.
AB  - The three common themes that underlie the induction and perpetuation of
      autoimmunity are genetic predisposition, environmental factors, and immune
      regulation. Environmental factors have gained much attention for their role in
      triggering autoimmunity, with increasing evidence of their influence as
      demonstrated by epidemiological studies, laboratory research, and animal studies.
      Environmental factors known to trigger and perpetuate autoimmunity include
      infections, gut microbiota, as well as physical and environmental agents. To
      address these issues, we will review major potential mechanisms that underlie
      autoimmunity including molecular mimicry, epitope spreading, bystander
      activation, polyclonal activation of B and T cells, infections, and
      autoinflammatory activation of innate immunity. The association of the gut
      microbiota on autoimmunity will be particularly highlighted by their interaction
      with pharmaceutical agents that may lead to organ-specific autoimmunity.
      Nonetheless, and we will emphasize this point, the precise mechanism of
      environmental influence on disease pathogenesis remains elusive. 

PMID- 25998915
TI  - Development of a reverse genetics system for epizootic hemorrhagic disease virus
      and evaluation of novel strains containing duplicative gene rearrangements.
AB  - Epizootic haemorrhagic disease is a non-contagious infectious viral disease of
      wild and domestic ruminants caused by epizootic hemorrhagic disease virus (EHDV).
      EHDV belongs to the genus Orbivirus within the family Reoviridae and is
      transmitted by insects of the genus Culicoides. The impact of epizootic
      haemorrhagic disease is underscored by its designation as a notifiable disease by
      the Office International des Epizooties. The EHDV genome consists of 10 linear
      dsRNA segments (Seg1-Seg10). Until now, no reverse genetics system (RGS) has been
      developed to generate replication-competent EHDV entirely from cloned cDNA,
      hampering detailed functional analyses of EHDV biology. Here, we report the
      generation of viable EHDV entirely from cloned cDNAs. A replication-competent
      EHDV-2 (Ibaraki BK13 strain) virus incorporating a marker mutation was rescued by
      transfection of BHK-21 cells with expression plasmids and in vitro synthesized
      RNA transcripts. Using this RGS, two additional modified EHDV-2 viruses were also
      generated: one that contained a duplex concatemeric Seg9 gene and another that
      contained a duplex concatemeric Seg10 gene. The modified EHDV-2 with a duplex
      Seg9 gene was genetically stable during serial passage in BHK-21 cells. In
      contrast, the modified EHDV-2 with a duplex Seg10 gene was unstable during serial
      passage, but displayed enhanced replication kinetics in vitro when compared with
      the WT virus. This RGS provides a new platform for the investigation of EHDV
      replication, pathogenesis and novel EHDV vaccines. 

PMID- 25998914
TI  - Type I interferonopathies--an expanding disease spectrum of immunodysregulation.
AB  - Type I interferons (IFNs) play a central role in the immune defense against viral
      infections. Type I IFN signaling is activated by pattern recognition receptors
      upon sensing of viral nucleic acids and induces antiviral programs through
      modulation of innate and adaptive immune responses. Type I interferonopathies
      comprise a heterogenous group of genetically determined diseases that are
      characterized by inappropriate activation of type I IFN. While their phenotypic
      spectrum is broad, ranging from severe neurological impairment to mild cutaneous
      disease, systemic autoinflammation, and autoimmunity are commonly shared signs of
      type I interferonopathies. Although the mechanisms underlying various disease
      phenotypes associated with inappropriate type I IFN activation have yet to be
      fully elucidated, our current understanding of the molecular pathogenesis of type
      I interferonopathies has provided a set of candidate molecules that can be
      interrogated in search of targeted therapies. 

PMID- 25998916
TI  - H5N1 influenza A virus with K193E and G225E double mutations in haemagglutinin is
      attenuated and immunogenic in mice.
AB  - Live-attenuated influenza vaccines (LAIVs) are now available for the prevention
      of influenza, with LAIV strains generally derived from serial passage in cultures
      or by reverse genetics (RG). The receptor-binding domain (RBD) in haemagglutinin
      (HA) of influenza virus is responsible for viral binding to the avian-type 2,3
      alpha-linked or human-type 2,6-alpha-linked sialic acid receptor; however, the
      virulence determinants in the RBD of H5N1 virus remain largely unknown. In the
      present study, serial passage of H5N1 virus A/Vietnam/1194/2004 in Madin-Darby
      canine kidney cells resulted in the generation of adapted variants with large
      plaque morphology, and genomic sequencing of selected variants revealed two
      specific amino acid substitutions (K193E and G225E) in the RBD. RG was used to
      generate H5N1 viruses containing either single or double substitutions in HA. The
      RG virus containing K193E and G225E mutations (rVN-K193E/G225E) demonstrated
      large-plaque morphology, enhanced replication and genetic stability after serial
      passage, without changing the receptor-binding preference. Importantly, in vivo
      virulence assessment demonstrated that rVN-K193E/G225E was significantly
      attenuated in mice. Microneutralization and haemagglutination inhibition assays
      demonstrated that immunization with rVN-K193E/G225E efficiently induced a robust
      antibody response against WT H5N1 virus in mice. Taken together, our experiments
      demonstrated that K193E and G225E mutations synergistically attenuated H5N1 virus
      without enhancing the receptor-binding avidity, and that the RG virus rVN
      K193E/G225E represents a potential H5N1 LAIV strategy that deserves further
      development. These findings identify the RBD as a novel attenuation target for
      live vaccine development and highlight the complexity of RBD interactions. 

PMID- 25998917
TI  - Relationship between hepcidin and GDF15 in anemic patients with type 2 diabetes
      without overt renal impairment.
AB  - AIMS: Despite the absence of overt renal impairment and decreased erythropoietin
      (EPO) levels, patients are usually anemic. Hepcidin, which is induced by
      inflammatory stimuli, plays an important role in anemia in chronic disease.
      Growth differentiation factor 15 (GDF15) is a putative anti-inflammatory cytokine
      that is elevated in type 2 diabetes (T2DM). Hence, we investigated the
      relationship between hepcidin and GDF15 in anemic T2DM patients without overt
      renal impairment. METHODS: Among 1150 patients who visited Kyungpook National
      University Hospital for T2DM between June 2006 and June 2014, we selected 55
      anemic patients without overt renal impairment (serum creatinine <1.5 mg/dL or
      estimated glomerular filtration rate >60 mL/min/1.73 m(2)) and other co-morbid
      diseases, including malignancy, thyroid disease, rheumatic arthritis, liver
      disease, iron-deficiency anemia and other endocrine disease. We measured
      anthropometric and metabolic parameters, as well as measured the serum iron,
      ferritin, interleukin-6 (IL-6), erythropoietin, hepcidin-25 and GDF15 levels.
      RESULTS: Anemic T2DM patients without overt renal impairment presented a greater
      inflammatory state, with increased serum hsCRP, ESR and IL-6 levels compared with
      non-anemic T2DM patients. Both hepcidin and GDF15 levels were increased and
      showed a positive correlation in anemic T2DM patients. CONCLUSION: In the absence
      of overt renal impairment, anemia in T2DM is associated with chronic
      inflammation, inducing elevation of hepcidin and GDF15 levels independently of
      the erythropoietin level.

PMID- 25998918
TI  - Cereulide food toxin, beta cell function and diabetes: Facts and hypotheses.
AB  - The incidence of both type 1 and type 2 diabetes is increasing and although
      environmental pollutants are believed to be potential culprits, the extent to
      which they can be held responsible remains uncertain. Some bacterial strains of
      the Bacillus cereus produce a toxin, cereulide, which is frequently found in
      starchy meals and which is difficult to eradicate from the food chain as it is
      highly resistant to heat, acidity and proteolysis. While cereulide is well known
      to cause acute emetic toxicity when ingested at high doses, several in vitro
      studies have shown that also extremely low doses of cereulide can be toxic, with
      beta cells being particularly sensitive. Mechanistically, such low doses impair
      the mitochondrial activity of the beta cells thereby leading to hampered insulin
      secretion and cell death, both key traits in the pathophysiology of diabetes. In
      vivo studies of chronic or repeated low dose exposure to cereulide are currently
      lacking, but should be performed to further clarify the true relevance of
      cereulide as a potential environmental contributor to the ongoing diabetes
      epidemic. 

PMID- 25998919
TI  - Gait analysis in Down syndrome pediatric patients using a sheet-type gait
      analyzer: Pilot study.
AB  - BACKGROUND: Children with Down syndrome (DS), who are likely to suffer from a
      large number of musculoskeletal problems, tend to have a unique pattern of
      walking in clinical settings. Despite such apparent uniqueness, few studies have
      empirically investigated gait development pattern in DS children, especially at
      an earlier age. We therefore conducted gait analysis in young DS children who are
      prescribed insoles, to explore how their gait patterns develop, using the gait
      parameters identified by Sutherland et al. as determinants of gait maturity of
      typical children. METHODS: Participants consisted of 63 DS children (31 boys)
      aged 1-6 years (mean, 4 years 1 month) with a diagnosis of flat feet who were
      prescribed orthotic insoles. A 2.4 m sheet-type gait analyzer was used to analyze
      gait pattern. We measured the following variables: walking velocity (cm/min),
      cadence (steps/min), step length (cm), and single-limb stance phase ratio (%),
      and examined their relationship with age on regression analysis. RESULTS: Walking
      velocity and step length were significantly and positively related to age.
      Cadence was also significantly, but negatively associated with age. In contrast,
      SLS phase ratio did not have a statistically significant relationship with age.
      CONCLUSION: Down syndrome children have unique gait development patterns.
      Although walking velocity, cadence, and step length were found to develop with
      age, as in typical children, SLS phase ratio did not change with age in DS
      children. Further studies with a larger sample are necessary to replicate these
      findings.

PMID- 25998920
TI  - Smoking-cessation advice to patients with chronic obstructive pulmonary disease:
      the critical roles of health insurance and source of care.
AB  - INTRODUCTION: Smoking cessation is the most effective therapeutic intervention
      for chronic obstructive pulmonary disease (COPD) patients. However, the
      proportion of smokers with COPD who have received physician advice to quit
      smoking is unknown. The purpose of this study is to assess the prevalence of
      receipt of smoking-cessation advice among adults with COPD and explore factors
      predicting advice receipt. METHODS: This study employed nationally representative
      data from the Medical Expenditure Panel Survey (MEPS), collected in 2008-2011 on
      adults aged >=20 years. Logistic regression models were conducted to estimate the
      likelihood of receiving provider advice. Data were analyzed in 2014. RESULTS:
      Four percent (95% CI=3.8%, 4.2%) of adults reported being diagnosed with COPD.
      Among them, 38.5% (95% CI=36.1%, 40.8%) were current smokers. Among those who had
      seen a physician in the past year, 85.6% (95% CI=83.1%, 88.0%) were advised to
      quit smoking. Logistic regression revealed negative associations between receipt
      of smoking-cessation advice and having fewer healthcare visits (AOR=0.41, 95%
      CI=0.23, 0.72); being uninsured (AOR=0.43, 95% CI=0.22, 0.83); having no usual
      source of care (AOR=0.39, 95% CI=0.19, 0.80); and having no comorbid chronic
      diseases (AOR=0.50, 95% CI=0.29, 0.85). CONCLUSIONS: Having no usual source of
      care and no health insurance are major barriers to receiving smoking-cessation
      advice among patients with COPD. The Patient Protection and Affordable Care Act
      has the potential to increase advice receipt in this high-risk population by
      expanding health insurance coverage and increasing the number of people with a
      usual source of care.

PMID- 25998921
TI  - Making policy practice in afterschool programs: a randomized controlled trial on
      physical activity changes.
AB  - INTRODUCTION: In the U.S., afterschool programs are asked to promote moderate to
      vigorous physical activity. One policy that has considerable public health
      importance is California's afterschool physical activity guidelines that indicate
      all children attending an afterschool program accumulate 30 minutes each day the
      program is operating. Few effective strategies exist for afterschool programs to
      meet this policy goal. The purpose of this study was to evaluate a multistep
      adaptive intervention designed to assist afterschool programs in meeting the 30
      minute/day moderate to vigorous physical activity policy goal. DESIGN: A 1-year
      group randomized controlled trial with baseline (spring 2013) and post-assessment
      (spring 2014). Data were analyzed 2014. SETTING/PARTICIPANTS: Twenty afterschool
      programs, serving >1,700 children (aged 6-12 years), randomized to either an
      intervention (n=10) or control (n=10) group. INTERVENTION: The employed
      framework, Strategies To Enhance Practice, focused on intentional programming of
      physical activity opportunities in each afterschool program's daily schedule and
      included professional development training to establish core physical activity
      competencies of staff and afterschool program leaders with ongoing technical
      assistance. MAIN OUTCOME MEASURES: The primary outcome was accelerometry-derived
      proportion of children meeting the 30-minute/day moderate to vigorous physical
      activity policy. RESULTS: Children attending intervention afterschool programs
      had an OR of 2.37 (95% CI=1.58, 3.54) to achieve the physical activity policy at
      post-assessment compared to control afterschool programs. Sex-specific models
      indicated that the percentage of intervention girls and boys achieving the
      physical activity policy increased from 16.7% to 21.4% (OR=2.85, 95% CI=1.43,
      5.68) and 34.2% to 41.6% (OR=2.26, 95% CI=1.35, 3.80), respectively. At post
      assessment, six intervention afterschool programs increased the proportion of
      boys achieving the physical activity policy to >=45% compared to one control
      afterschool program, whereas three intervention afterschool programs increased
      the proportion of girls achieving physical activity policy to >=30% compared to
      no control afterschool programs. CONCLUSIONS: The Strategies To Enhance Practice
      intervention can make meaningful changes in the proportion of children meeting
      the moderate to vigorous physical activity policy within one school year.
      Additional efforts are required to enhance the impact of the intervention.

PMID- 25998922
TI  - An economic evaluation of colorectal cancer screening in primary care practice.
AB  - INTRODUCTION: Recent colorectal cancer screening studies focus on optimizing
      adherence. This study evaluated the cost effectiveness of interventions using
      electronic health records (EHRs); automated mailings; and stepped support
      increases to improve 2-year colorectal cancer screening adherence. METHODS:
      Analyses were based on a parallel-design, randomized trial in which three stepped
      interventions (EHR-linked mailings ["automated"]; automated plus telephone
      assistance ["assisted"]; or automated and assisted plus nurse navigation to
      testing completion or refusal [navigated"]) were compared to usual care. Data
      were from August 2008 to November 2011, with analyses performed during 2012-2013.
      Implementation resources were micro-costed; research and registry development
      costs were excluded. Incremental cost-effectiveness ratios (ICERs) were based on
      number of participants current for screening per guidelines over 2 years.
      Bootstrapping examined robustness of results. RESULTS: Intervention delivery cost
      per participant current for screening ranged from $21 (automated) to $27
      (navigated). Inclusion of induced testing costs (e.g., screening colonoscopy)
      lowered expenditures for automated (ICER=-$159) and assisted (ICER=-$36) relative
      to usual care over 2 years. Savings arose from increased fecal occult blood
      testing, substituting for more expensive colonoscopies in usual care. Results
      were broadly consistent across demographic subgroups. More intensive
      interventions were consistently likely to be cost effective relative to less
      intensive interventions, with willingness to pay values of $600-$1,200 for an
      additional person current for screening yielding >=80% probability of cost
      effectiveness. CONCLUSIONS: Two-year cost effectiveness of a stepped approach to
      colorectal cancer screening promotion based on EHR data is indicated, but longer
      term cost effectiveness requires further study.

PMID- 25998923
TI  - Racial and ethnic differences in health behaviors among cancer survivors.
AB  - INTRODUCTION: Previous studies of health behaviors of adult cancer survivors have
      not adequately examined racial and ethnic differences because of small sample
      sizes. A national data set was used to examine differences in health behaviors
      between cancer survivors and controls and between racial and ethnic groups among
      survivors. METHODS: The study analyzed 2009 Behavioral Risk Factor Surveillance
      System survey data in 2012-2014. Descriptive statistics were used to examine
      differences in health behaviors between cancer survivors and controls aged 20-64
      years. Multivariable analysis was conducted to examine associations between
      race/ethnicity (white, African American, Hispanic, Asian, or Native American) and
      health behaviors (BMI, fruit and vegetable consumption, physical activity, and
      smoking status) while adjusting for demographic and medical characteristics.
      Significance was set at p<0.01. RESULTS: Compared with controls (n=245,283),
      cancer survivors (n=17,158) had higher prevalence rates for overweight/obese
      status (67% vs 65%); not meeting physical activity recommendations (53% vs 49%);
      and current smoking status (22% vs 20%). In the multivariable model, diet and
      smoking behavior differed across cancer status. African American (AOR=1.95) and
      Hispanic (AOR=2.06) survivors were more likely to have higher BMI than white
      survivors. African American survivors (AOR=1.6) were less likely to meet physical
      activity guidelines. Native American (AOR=3.08) and multiracial (AOR=1.74)
      survivors were more likely to be current smokers than non-Hispanic white
      survivors. CONCLUSIONS: This study suggests that racial and ethnic differences
      exist in the adoption of recommended health behaviors; future research should
      identify factors to reduce these differences.

PMID- 25998924
TI  - Prior Depression and Health Insurance in Non-receipt of Needed Medical Services.
AB  - INTRODUCTION: Rates of non-access to needed medical services are elevated among
      uninsured and sociodemographic subpopulations. Clinical depression is associated
      with comorbid medical illness and reduced treatment adherence. The purpose of
      this study was to examine whether prior depression predicts missed needed medical
      care independent of health insurance status and socioeconomic and demographic
      characteristics. METHODS: Data were from a cross-sectional representative sample
      of adult New York City residents, surveyed through the 2009 (n=9,900) and 2010
      (n=8,622) annual Community Health Survey. Logistic regression was used to
      evaluate the association of lifetime depression with missed needed medical care
      in the past year, with stratification by health insurance status and adjustment
      for socioeconomic characteristics. Analyses were performed in 2014. RESULTS:
      Prior depression was associated with missed needed medical care among both
      insured (OR=1.9, 95% CI=1.7, 2.2) and uninsured adults (OR=1.8, 95% CI=1.3, 2.4).
      Missed needed care report was associated with uninsured status (OR=3.6, 95%
      CI=3.1, 4.0), controlling for employment, income, and demographics. CONCLUSIONS:
      Prior depression corresponded to greater probability of missed needed medical
      care report in the previous year, independent of health insurance status,
      employment, income, and demographics.

PMID- 25998927
TI  - Recommendation for mental health benefits legislation.

PMID- 25998925
TI  - Evaluating diabetes health policies using natural experiments: the natural
      experiments for translation in diabetes study.
AB  - The high prevalence and costs of type 2 diabetes makes it a rapidly evolving
      focus of policy action. Health systems, employers, community organizations, and
      public agencies have increasingly looked to translate the benefits of promising
      research interventions into innovative policies intended to prevent or control
      diabetes. Though guided by research, these health policies provide no guarantee
      of effectiveness and may have opportunity costs or unintended consequences.
      Natural experiments use pragmatic and available data sources to compare specific
      policies to other policy alternatives or predictions of what would likely have
      happened in the absence of any intervention. The Natural Experiments for
      Translation in Diabetes (NEXT-D) Study is a network of academic, community,
      industry, and policy partners, collaborating to advance the methods and practice
      of natural experimental research, with a shared aim of identifying and
      prioritizing the best policies to prevent and control diabetes. This manuscript
      describes the NEXT-D Study group's multi-sector natural experiments in areas of
      diabetes prevention or control as case examples to illustrate the selection,
      design, analysis, and challenges inherent to natural experimental study
      approaches to inform development or evaluation of health policies.

PMID- 25998926
TI  - Effects of mental health benefits legislation: a community guide systematic
      review.
AB  - CONTEXT: Health insurance benefits for mental health services typically have paid
      less than benefits for physical health services, resulting in potential
      underutilization or financial burden for people with mental health conditions.
      Mental health benefits legislation was introduced to improve financial protection
      (i.e., decrease financial burden) and to increase access to, and use of, mental
      health services. This systematic review was conducted to determine the
      effectiveness of mental health benefits legislation, including executive orders,
      in improving mental health. EVIDENCE ACQUISITION: Methods developed for the Guide
      to Community Preventive Services were used to identify, evaluate, and analyze
      available evidence. The evidence included studies published or reported from 1965
      to March 2011 with at least one of the following outcomes: access to care,
      financial protection, appropriate utilization, quality of care, diagnosis of
      mental illness, morbidity and mortality, and quality of life. Analyses were
      conducted in 2012. EVIDENCE SYNTHESIS: Thirty eligible studies were identified in
      37 papers. Implementation of mental health benefits legislation was associated
      with financial protection (decreased out-of-pocket costs) and appropriate
      utilization of services. Among studies examining the impact of legislation
      strength, most found larger positive effects for comprehensive parity legislation
      or policies than for less-comprehensive ones. Few studies assessed other mental
      health outcomes. CONCLUSIONS: Evidence indicates that mental health benefits
      legislation, particularly comprehensive parity legislation, is effective in
      improving financial protection and increasing appropriate utilization of mental
      health services for people with mental health conditions. Evidence was limited
      for other mental health outcomes.

PMID- 25998928
TI  - Is vitamin B12 deficiency a risk factor for cardiovascular disease in
      vegetarians?
AB  - The goal of this paper is to describe the role of vitamin B12 deficiency in
      cardiovascular disease development among vegetarians. Vegetarians have a high
      prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated
      with a variety of atherogenic processes that are mainly, but not exclusively, due
      to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-MUmol/L increase
      above 10 MUmol/L of serum homocysteine is associated with a 20% increased risk of
      circulatory health problems. Mean homocysteine concentration >10 MUmol/L among
      vegetarians was reported in 32 of 34 reports. Macrocytosis associated with
      vitamin B12 deficiency is also associated with fatal and non-fatal coronary
      disease, myocardial infarction, stroke, and other circulatory health problems.
      Compared with non-vegetarians, vegetarians have an improved profile of the
      traditional cardiovascular disease risk factors, including serum lipids, blood
      pressure, serum glucose concentration, and weight status. However, not all
      studies that assessed cardiovascular disease incidence among vegetarians reported
      a protective effect. Among studies that did show a lower prevalence of
      circulatory health problems, the effect was not as pronounced as expected, which
      may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12
      deficiency may negate the cardiovascular disease prevention benefits of
      vegetarian diets. In order to further reduce the risk of cardiovascular disease,
      vegetarians should be advised to use vitamin B12 supplements. 

PMID- 25998929
TI  - Changes in Internet searches associated with the "Tips from Former Smokers"
      campaign.

PMID- 25998930
TI  - Characterization and antagonistic properties of Streptomyces strains isolated
      from Saharan soils, and evaluation of their ability to control seedling blight of
      barley caused by Fusarium culmorum.
AB  - During a screening for potential plant disease control actinomycetes, a total of
      133 strains were isolated from Saharan soil samples of seven Algerian regions by
      dilution technique on chitin-vitamins agar medium. Screening for antagonistic
      properties using streak assay method showed that 25% of isolates demonstrated
      strong activities against a wide range of plant pathogenic fungi. Due to their
      strong anti-Fusarium activities, six of these isolates were selected and
      subsequently related to Streptomyces species by polyphasic analysis. These
      isolates were evaluated for their biocontrol ability against Fusarium culmorum, a
      serious pathogenic fungus of cereals crops related to damping-off and seedling
      blight resulting in yield loss. Barley seeds were chosen as cereal plant model.
      Surface bacterized seeds with TW3, RI3 and TW2 strains expressed the highest
      performances and permit to reduce significantly both the disease occurrence on
      seedlings (62-76%) and the extent of seedling blight symptoms (over than 95%).
      However, a negative effect on plant establishment was observed for RI3 treatment.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The genus Fusarium is considered to be one
      of the most problematic phytopathogenic fungi for crop culture worldwide. Inside
      this genus, F. culmorum is the aetiological agent of seedling blight in various
      monocotyledonous plants such as barley and cause extensive yield and quality
      losses in humid and semi-humid regions. Biological control may be a successful
      alternative to chemical control, particularly with the controversy surrounding
      the use of the fungicides and the limited obtained results to control F.
      culmorum. This study highlights the effectiveness of some antagonistic
      Streptomyces isolated from Algerian Saharan soils to control F. culmorum by the
      reduction in disease occurrence and disease severity suggesting their use on
      microbial biocontrol formulation against soilborne diseases.

PMID- 25998931
TI  - Hepatitis B virus upregulates the expression of kinesin family member 4A.
AB  - Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular
      carcinoma (HCC). Kinesin family member 4A (KIF4A) is a microtubule-based motor
      protein, which is upregulated in cervical and lung cancer. However, the
      expression of KIF4A in HBV-associated HCC, and the effect of HBV on the
      expression of KIF4A remain to be elucidated. In the present study, the expression
      profiles of KIF4A were examined in cancerous tissues and paracancerous tissues
      from patients with HCC, who presented with histories of chronic HBV infection,
      and the role of HBV in the induction of the expression of KIF4A was investigated.
      HepG2 cells were transfected with the pHBV1.3, HBV infectious clone and a
      construct, which contained the luciferase gene under the control of the KIF4A
      gene promoter. The results demonstrated that the expression of KIF4A was
      significantly higher in the HCC tissues than in the paracancerous tissues. HBV
      activated the KIF4A gene promoter and upregulated the mRNA and protein expression
      of KIF4A. Furthermore, activation of the gene expression of KIF4A increased in a
      pHBV1.3 concentration-dependent manner. These results provide novel insights into
      the understanding of HCC oncogenesis caused by HBV.

PMID- 25998932
TI  - Factors affecting redox potential and differential sensitivity of SoxR to redox
      active compounds.
AB  - SoxR is a [2Fe-2S]-containing sensor-regulator, which is activated through
      oxidation by redox-active compounds (RACs). SoxRs show differential sensitivity
      to RACs, partly due to different redox potentials, such that Escherichia coli
      (Ec) SoxR with lower potential respond to broader range of RACs than Streptomyces
      coelicolor (Sc) SoxR. In S. coelicolor, the RACs that do not activate ScSoxR did
      not inhibit growth, suggesting that ScSoxR is tuned to respond to growth
      inhibitory RACs. Based on sequence comparison and mutation studies, two critical
      amino acids around the [2Fe-2S] binding site were proposed as key determinants of
      sensitivity. ScSoxR-like mutation (R127L/P131V) in EcSoxR changed its sensitivity
      profile as ScSoxR, whereas EcSoxR-like mutation (L126R/V130P) in ScSoxR caused
      relaxed response. In accordance, the redox potentials of EcSoxR(R) (127) (L) (/)
      (P) (131) (V) and ScSoxR(L126R/V130P) were estimated to be -192 +/- 8 mV and -273
      +/- 10 mV, respectively, approaching that of ScSoxR (-185 mV) and EcSoxR (-290
      mV). Molecular dynamics simulations revealed that the R127L and P131V
      substitutions in EcSoxR caused more electropositive environment around [2Fe-2S],
      making it harder to get oxidized. This reveals a mechanism to modulate redox
      potential in [Fe-S]-containing sensors by point mutations and to evolve a sensor
      with differential sensitivity to achieve optimal cellular physiology. 

PMID- 25998933
TI  - Effects of Retinal Angiography on Optical Coherence Tomography Measurements.
AB  - PURPOSE: To evaluate the effects of retinal angiography, using fluorescein and
      indocyanine green dyes, on optical coherence tomography (OCT) measurements.
      METHODS: In total, 76 eyes from 76 consecutive patients were included. Macular
      cube 512 * 128 combination scanning and optic disc 200 * 200 scanning using
      spectral-domain (SD)-OCT were performed twice, before and after retinal
      angiography, with fluorescein or indocyanine green. Signal strength, regional
      retinal thickness of the 9 Early Treatment Diabetic Retinopathy Study subfields,
      total macular volume, and retinal nerve fiber layer thickness obtained before and
      after angiography were compared. Repeatability was also investigated. RESULTS:
      Comparing the results of OCT measured before and after retinal angiography, there
      was no statistically significant difference in any parameter assessed. The
      interclass correlation values for each measurement were all >0.808 (range 0.808
      0.999). CONCLUSION: Retinal angiography using fluorescein and indocyanine green
      dyes has no significant effect on OCT measurements.

PMID- 25998934
TI  - The efficacy of a tissue-engineered xenograft in conjunction with sodium
      hyaluronate carrier in maxillary sinus augmentation: a clinical study.
AB  - PepGen P-15 Putty comprises anorganic bovine bone matrix (ABM) coupled with a
      synthetic cell-binding peptide, suspended in a sodium hyaluronate carrier. The P
      15 portion exhibits a similar structure and properties to the cell-binding region
      of type I collagen. This study was performed to evaluate ABM/P-15 putty as the
      sole graft in sinus augmentation. Ten patients for whom both a sinus augmentation
      and two implants were indicated in the posterior maxilla were enrolled. Bone
      cores were harvested at 8 and 16 weeks, followed by placement of one implant at 8
      weeks and the second at 16 weeks. Twenty collected bone cores were evaluated
      histologically and by micro-computed tomography. Results showed a significant
      increase (P<0.05) in bone mineral density at 8 weeks (0.70+/-0.13g/cm(3)) and 16
      weeks (0.97+/-0.08g/cm(3)) in the graft compared to native (control) bone (0.04+/
      0.02g/cm(3)). There was no significant difference (P>0.05) in the percentage bone
      volume at the two time intervals (PBV 21.14+/-4.56 at 8 weeks and 26.33+/-5.60 at
      16 weeks). The average increase in bone height at 16 weeks was 10.55+/-0.53mm. It
      is concluded that PepGen P-15 Putty is capable of conducting and accelerating new
      bone formation and can successfully support dental implants.

PMID- 25998935
TI  - Sulcular translation flap in secondary bone grafting: retrospective study of 72
      alveolar clefts.
AB  - Secondary bone grafting from the iliac crest is the gold standard in the
      reconstruction of maxillary alveolar bone defects in cleft patients. Numerous
      techniques for this graft have been described, although none is considered
      clearly superior at this time. A retrospective chart study was performed of 72
      alveolar clefts in 59 patients who underwent an alveolar iliac crest bone graft
      with nasal floor reconstruction, with or without concomitant secondary
      cheilorhinoplasty. Forty-four patients were included in the bone grafting group
      and 15 in the concomitant cheilorhinoplasty group. Both groups had a sulcular
      translation mucoperiosteal flap with anterior repositioning of the gingival
      papilla as the preferred intraoral flap technique. One-third of patients had
      undergone previous attempts at oronasal fistula closure. Results showed 100%
      Bergland stage 1 in the cheilorhinoplasty group and 96% in the bone graft group.
      Two failures (stage 4) were observed in the bone graft group. The infection rate
      was 9% in the cheilorhinoplasty group and 2% in the bone graft group. Of clefts
      in the bone graft group, 10% showed postoperative residual fistulas; none were
      observed in the cheilorhinoplasty group. The sulcular translation flap is a
      simple surgical approach and shows a low complication rate. 

PMID- 25998936
TI  - Assessing the potential of the Woman's Condom for vaginal drug delivery.
AB  - BACKGROUND: The Woman's Condom is a new female condom that uses a dissolvable
      polyvinyl alcohol capsule to simplify vaginal insertion. This preclinical study
      assessed the feasibility to incorporate an antiviral drug, UC781, into the
      Woman's Condom capsule, offering a unique drug delivery platform. STUDY DESIGN:
      UC781 capsules were fabricated using methods from the development of the Woman's
      Condom capsules as well as those used in vaginal film development. Capsules were
      characterized to evaluate physical/chemical attributes, Lactobacillus
      compatibility, in vitro safety and bioactivity, and condom compatibility.
      RESULTS: Two UC781 capsule platforms were assessed. Capsule masses (mg; mean+/
      SD) for platforms 1 and 2 were 116.50+/-18.22 and 93.80+/-8.49, respectively.
      Thicknesses were 0.0034+/-0.0004 in and 0.0033+/-0.0004 in. Disintegration times
      were 11+/-3 s and 5+/-1 s. Puncture strengths were 21.72+/-3.30 N and 4.02+/-0.83
      N. Water content measured 6.98+/-1.17% and 7.04+/-1.92%. UC781 content was 0.59+/
      0.05 mg and 0.77+/-0.11 mg. Both platforms retained in vitro bioactivity and were
      nontoxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules
      with the Woman's Condom pouch did not decrease condom mechanical integrity.
      CONCLUSIONS: UC781 was loaded into a polymeric capsule similar to that of the
      Woman's Condom product. This study highlights the potential use of the Woman's
      Condom as a platform for vaginal delivery of drugs relevant to
      sexual/reproductive health, including those for short- or long-acting HIV
      prevention. IMPLICATIONS: We determined the proof-of-concept feasibility of
      incorporation of an HIV-preventative microbicide into the Woman's Condom capsule.
      This study highlights various in vitro physical and chemical evaluations as well
      as bioactivity and safety assessments necessary for vaginal product development
      related to female sexual and reproductive health.

PMID- 25998937
TI  - Nonuse of contraception among women at risk of unintended pregnancy in the United
      States.
AB  - OBJECTIVE: This paper seeks to determine factors associated with nonuse of
      contraception by women at risk of unintended pregnancy in the United States. This
      nonuse may be associated with about 900,000 unintended births in the US each
      year. STUDY DESIGN: The 2002 and 2006-2010 National Surveys of Family Growth were
      combined to yield a nationally representative sample of 9,445 women at risk of
      unintended pregnancy. Logistic regression analyses identified factors associated
      with nonuse of contraception. RESULTS: This analysis reveals previously
      undocumented patterns of nonuse: controlling for confounding variables,
      cohabiting women [adjusted odds ratio (AOR)=2.3, 95% confidence interval
      (CI)=1.45-3.52] had higher odds of nonuse than married women; women who reported
      a difficulty getting pregnant (AOR=2.5, 95% CI=2.01-3.01) had higher odds of
      nonuse than those who did not. Nonuse was also more common among women with a
      master's degree or more (AOR=1.5, 95% CI=1.11-2.08) compared with those with some
      college or bachelor's degree, and it was more common among women in their first
      year after first intercourse than after the first year (AOR 1.6, 95% CI=1.12
      2.22). Among women who had a recent unintended birth, the most common reason for
      not using contraception prior to conception was that she did not think she could
      get pregnant. CONCLUSIONS: This study establishes national estimates of reasons
      for nonuse of contraception and identifies some new subgroups at risk of nonuse.
      IMPLICATIONS: These results may help better understand factors affecting nonuse
      of contraception and develop strategies for preventing unintended pregnancy in
      the United States.

PMID- 25998938
TI  - Induction of fetal demise before pregnancy termination: practices of family
      planning providers.
AB  - OBJECTIVES: Our survey aimed to characterize the practice of inducing fetal
      demise before pregnancy termination among abortion providers, including its
      technical aspects and why providers have chosen to adopt it. STUDY DESIGN: We
      conducted a survey of Family Planning Fellowship-trained or Fellowship-affiliated
      Family Planning (FP) subspecialists about their practice of inducing fetal
      demise, including questions regarding the circumstances in which they would
      induce demise, techniques used and rationales for choosing whether to adopt this
      practice. RESULTS: Of the 169 FP subspecialists we surveyed, 105 (62%) responded.
      About half (52%) of respondents indicated that they routinely induced fetal
      demise before terminations in the second trimester. Providers' practices varied
      in the gestations at which they started inducing demise as well as the techniques
      used. Respondents provided legal, technical and psychological reasons for their
      decisions to induce demise. CONCLUSION: Inducing fetal demise before second
      trimester abortions is common among US FP specialists for multiple reasons. The
      absence of professional guidelines or robust data may contribute to the variance
      in the current practice patterns of inducing demise. IMPLICATIONS: Our study
      documents the widespread practice of inducing fetal demise before second
      trimester abortion and further describes wide variation in providers' methods and
      rationales for inducing demise. It is important for abortion providers as a
      professional group to come to a formal consensus on the appropriate use of these
      techniques and to determine whether such practices should be encouraged,
      tolerated or even permitted.

PMID- 25998939
TI  - Apoptosis inhibitor TRIAP1 is a novel effector of drug resistance.
AB  - TP53-regulated inhibitor of apoptosis 1 (TRIAP1) is a novel apoptosis inhibitor
      that binds HSP70 in the cytoplasm and blocks the formation of the apoptosome and
      caspase-9 activation. TRIAP1 has been shown to be upregulated in many types of
      cancers; however, its role remains elusive. We determined the TRIAP1 mRNA levels
      in a panel of human tissues and found its expression to be ubiquitous. Normal
      breast, as well as non-tumorigenic breast cells, exhibited lower TRIAP1 mRNA
      levels than breast cancer cells or their drug-resistant derivatives. TRIAP1 is a
      small, evolutionarily conserved protein that is 76 amino acids long. We found
      that yeast cells, in which the TRIAP1 homologue was knocked out, had increased
      sensitivity to doxorubicin. Equally, RNA interference in breast cancer drug
      resistant cells demonstrated that downregulation of TRIAP1 impaired cell growth
      in the presence of doxorubicin. As expected, caspase-9 activation was diminished
      after overexpression of TRIAP1 in drug-resistant cells. Importantly, stable
      transfections of a TRIAP1 expression plasmid in CAL51 cells led to a marked
      increase in the number of doxorubicin-resistant clones, that was abolished when
      cells expressed hairpins targeting TRIAP1. In addition, we showed that TRIAP1
      expression was also triggered by estrogen deprivation in MCF-7 cells. Although
      both polyclonal and monoclonal antibodies generated for the present study failed
      to robustly detect TRIAP1, we demonstrated that TRIAP1 represents a novel marker
      for drug resistance in breast cancer cells and it may be used in the
      stratification of breast cancer patients once a suitable antibody has been
      developed. Equally, these studies open potential drug development strategies for
      blocking TRIAP1 activity and avoiding drug resistance.

PMID- 25998940
TI  - Which factors are associated with quality of life in patients with Graves'
      orbitopathy presenting for orbital decompression surgery?
AB  - PURPOSE: Graves' orbitopathy (GO) is associated with changes in the appearance of
      the eyes and visual dysfunction. Patients report feeling socially isolated and
      unable to continue with day-to-day activities. This study aimed at investigating
      the demographic, clinical, and psychosocial factors associated with quality of
      life in patients presenting for orbital decompression surgery. METHODS: One
      hundred and twenty-three adults with GO due for orbital decompression at
      Moorfields Eye Hospital London were recruited prospectively. Clinical measures
      including treatment history, exophthalmos, optic neuropathy, and diplopia were
      taken by an ophthalmologist. Participants completed psychosocial questionnaires,
      including the Graves' Ophthalmopathy Quality of Life Scale (GO-QOL), the Hospital
      Anxiety and Depression Scale, and the Derriford Appearance Scale. Hierarchical
      multiple regression analyses were used to identify predictors of quality of life.
      RESULTS: Higher levels of potential cases of clinical anxiety (37%) and
      depression (26%) were found in this study sample than in patients with other
      chronic diseases or facial disfigurements. A total of 55% of the variance in GO
      QOL visual function scores was explained by the regression model; age,
      asymmetrical GO and depressed mood were significant unique contributors. In all,
      75% of the variance in GO-QOL appearance scores was explained by the regression
      model; gender, appearance-related cognitions and depressed mood were significant
      unique contributors. CONCLUSION: Appearance-related quality of life and mood were
      particularly affected in this sample. Predominantly psychosocial characteristics
      were associated with quality of life. It is important when planning surgery for
      patients that clinicians be aware of factors that could potentially influence
      outcomes.

PMID- 25998941
TI  - Congenital high myopia and central macular atrophy: a report of 3 families.
AB  - AIMS: To report the clinical phenotype in a series of four children from three
      families with the rare association of high myopia, central macular atrophy, and
      normal full-field electroretinography (ERG). METHODS: Four male patients were
      ascertained with reduced vision, nystagmus, and atrophy of the macula from early
      childhood. Patients underwent full ophthalmic examination, electrophysiological
      testing, and retinal imaging. RESULTS: Minimum duration of follow-up was 8 years.
      At last review, visual acuity ranged from 0.22 to 1.20 logMAR (6/9.5-6/95
      Snellen) at a mean age of 10.5 years (median 9.5 years, range 9-14 years).
      Refractive error ranged from a spherical equivalent of -7.40 D to -24.00 D. Three
      had convergent squint. Fundus examination and imaging demonstrated bilateral
      macular atrophy in all patients that varied from mild atrophy of the retinal
      pigment epithelium (RPE) to well-demarcated, punched-out atrophic lesions of
      retina, RPE, and choroid. Flash ERG was normal under photopic and scotopic
      conditions in all patients. Pattern ERG, performed in three patients, was
      consistent with mild to severe macular dysfunction. Progression of the area of
      atrophy was evident in one patient and of the myopia in two patients but all
      patients had stable visual acuity. CONCLUSIONS: Patients with congenital high
      myopia and macular atrophy present in infancy with reduced visual acuity and
      nystagmus. The macular atrophic lesions vary in size and severity but
      electrophysiological testing is consistent with dysfunction confined to the
      macula. There was no deterioration in visual acuity over 8-10 years of
      monitoring.

PMID- 25998942
TI  - Long-term evaluation of dexamethasone intravitreal implant in vitrectomized and
      non-vitrectomized eyes with macular edema secondary to non-infectious uveitis.
AB  - PURPOSE: To compare dexamethasone (DEX) intravitreal implant effect in non
      vitrectomized (non-PPV) vs vitrectomized (PPV) eyes with macular edema (ME)
      secondary to non-infectious uveitis. METHODS: Medical records of patients with
      uveitic ME treated with DEX-intravitreal implant were reviewed. Main outcome
      measures were changes in central retinal thickness (CRT), best corrected visual
      acuity (BCVA), intraocular pressure (IOP), vitreous haze and adverse events.
      Statistical analysis was performed by Longitudinal Linear model using the General
      Estimating Equation methodology. RESULTS: Forty-two eyes of 32 patients were
      included. Median follow-up time was 18 months (interquartile range (IQR): 12-24).
      Median CRT showed its maximum decrease at the first month in non-PPV and PPV eyes
      without statistically significant differences between both groups (P=NS). Median
      Snellen BCVA, converted to logarithm (LogMAR), showed its maximum improvement at
      third month in both groups without statistically significant differences between
      them (P=NS). Median IOP was higher in non-PPV eyes than in PPV eyes from third
      (P=0.025) to 12th month (P=0.013). Vitreous haze score improved in both groups
      since first month and showed no differences (P=0.706). Reinjection was performed
      in 45.2% of eyes at a median time of 5 months IQR: (5-6). Ocular hypertension
      (47.6%) was the most common adverse event. CONCLUSIONS: DEX-intravitreal implant
      for uveitic ME has similar long-term safety profile and good response measured in
      terms of CRT decrease, BCVA, and vitreous haze improvement in both groups. Non
      PPV eyes following DEX-intravitreal implant showed higher IOP increase than PPV
      eyes, showing the need for close IOP monitoring.

PMID- 25998943
TI  - Patient satisfaction with Peninsula Optometry Community Glaucoma Scheme.

PMID- 25998944
TI  - Determination of macular hole size in relation to individual variabilities of
      fovea morphology.
AB  - PURPOSE: To determine the preoperative anatomic factors in macular holes and
      their correlation to hole closure. METHODS: Forty-six eyes with consecutive
      unilateral macular hole who had undergone surgery and followed up for at least 6
      months were enrolled. Optical coherence tomography images and best-corrected
      visual acuity (BCVA) within 2 weeks prior to operation and 6 months after surgery
      were analyzed. The maximal hole dimension, foveal degeneration factors (inner
      nuclear layer cysts, outer segment (OS) shortening) and the widest foveolar floor
      size of the fellow eyes were measured. For overcoming preoperative individual
      variability of foveal morphology, an 'adjusted' hole size parameter (the ratio
      between the hole size and the fellow eye foveolar floor size) was used based on
      the fact that both eyes were morphologically symmetrical. RESULTS: Mean
      preoperative BCVA (logMAR) was 1.03+/-0.43 and the mean postoperative BCVA was
      0.50+/-0.38 at 6 months. Preoperative BCVA is significantly associated with
      postoperative BCVA (P=0.0002). The average hole diameter was 448.9+/-196.8 MUm
      and the average fellow eye foveolar floor size was 461.3+/-128.4 MUm. There was a
      correlation between hole diameter and the size of the fellow eye foveolar floor
      (Pearson's coefficient=0.608, P<0.0001). The adjusted hole size parameter was
      0.979+/-0.358 (0.761-2.336), which was a strong predictor for both anatomic
      (P=0.0281) and visual (P=0.0016) outcome. CONCLUSION: When determining the extent
      of preoperative hole size, we have to take into consideration the foveal
      morphologic variations among individuals. Hole size may be related to the
      original foveal shape, especially in relation to the centrifugal retraction of
      the foveal tissues.

PMID- 25998945
TI  - Safety and efficacy of simultaneous bilateral 25-gauge lens-sparing vitrectomy
      for vascularly active stage 4 retinopathy of prematurity.
AB  - PURPOSE: To report the safety and efficacy of simultaneous bilateral 25-gauge
      lens-sparing vitrectomy for vascularly active stage 4 retinopathy of prematurity
      (ROP). METHODS: Retrospective, noncomparative, consecutive case series. Twenty
      eyes of 10 babies who presented with vascularly active stage 4 ROP in both the
      eyes underwent simultaneous bilateral 25-gauge lens-sparing vitrectomy. After
      completing surgery for one eye, the other eye was re-prepped as performed before
      starting any new case of a different patient and an entire new set of disposable
      25-gauge instruments were used. During the post-operative period parents were
      advised to keep separate eye drops for each eye and to wash their hands in
      between switching the eyes to put the drops. RESULTS: The mean follow-up was 8.7
      months (range 4-17 months). None of the cases developed any signs of infection.
      The anatomic success rate for stage 4a was 100% (11/11 eyes) and for stage 4b was
      8/9 eyes (89%). CONCLUSION: These results show that simultaneous bilateral 25
      gauge lens-sparing vitrectomy for stage 4 ROP is a safe and effective procedure
      with a good outcome provided both eyes of the baby are treated as eyes of two
      different patients.

PMID- 25998946
TI  - Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome
      in Asian Indians.
AB  - PURPOSE: To study the clinical and histopathological features of eyelid sebaceous
      gland carcinoma (SGC) and to evaluate the prognosis in the Asian-Indian
      population. METHODS: This is a retrospective study of 191 patients with SGC.
      RESULTS: The mean age at presentation of eyelid SGC was 57 years (median, 56
      years). The tumor epicenter was most commonly located in the upper eyelid (n=125,
      65%). The mean tumor basal diameter was 15 mm (median, 10 mm). There was evidence
      of tumor extension into the orbit (n=30, 16%), paranasal sinuses (n=3, 2%), and
      brain (n=1, 1%). Wide excision biopsy (n=146, 78%) was the most common treatment
      modality. Tumor recurrence was noted in 42 (24%) patients over a mean follow-up
      period of 29 months (median, 20 months). On the basis of the Kaplan-Meier
      estimate, lymph node metastasis occurred in 18%, systemic metastasis was detected
      in 10%, and death occurred in 2% of patients at 10 years. On multivariate
      analysis, the factors predicting locoregional lymph node and systemic metastasis
      were medial canthal involvement (P=0.004; P=0.013), lateral canthal involvement
      (P=0.013; P=0.025), tumor basal diameter >10 mm (P=0.002; P=0.002), and
      perivascular invasion (P=0.043; P<0.001), respectively. The factors predicting
      death due to metastasis on multivariate analysis were medial canthal involvement
      (P=0.012) and tumor basal diameter >10 mm (P=0.001). CONCLUSION: Advanced eyelid
      SGC is a tumor associated with poor prognosis. In this study, canthal
      involvement, larger tumor diameter, and perivascular invasion were poor
      prognostic factors.

PMID- 25998947
TI  - A fluorescent tool set for yeast Atg proteins.
AB  - Fluorescence microscopy of live cells is instrumental in deciphering the
      molecular details of autophagy. To facilitate the routine examination of yeast
      Atg proteins under diverse conditions, here we provide a comprehensive tool set,
      including (1) plasmids for the expression of GFP chimeras at endogenous levels
      for most Atg proteins, (2) RFP-Atg8 constructs with improved properties as a PAS
      marker, and (3) plasmids for the complementation of common yeast auxotrophic
      markers. We hope that the availability of this tool set will further accelerate
      yeast autophagy research. 

PMID- 25998948
TI  - Confronting the missing epistasis problem: on the reproducibility of gene-gene
      interactions.
AB  - Epistasis (gene-gene interaction) is thought to play an integral role in the
      genetic basis of complex traits, and a significant amount of research has been
      invested into identifying this phenomenon in human disease. However, the overall
      success of empirical studies of epistasis in humans is unclear, as such studies
      are rarely systematically evaluated. Here, we have selected asthma as an example
      of a well-studied, complex human disease, and provide a critical analysis and
      replication attempt of nearly all prior reports of epistasis for this disease. Of
      191 previously reported interactions, we find that 39.8% were not originally
      identified using an explicit test for interaction and thus may not have been true
      epistatic effects to begin with. Moreover, directions of effect were not
      described for 46.1% of the interactions, which prevents their rigorous
      replication. In the original studies, attempts at replication were made for 15.2%
      of the interactions, and 7.3% were actually replicated. In the current study, we
      were able to evaluate 85.9% of the interactions using a large asthma dataset from
      the GABRIEL Consortium. None of these interactions could be replicated based on
      strict criteria. However, we found nominally significant (p < 0.05) evidence in
      support of 23.8% of the evaluated interactions. Although many reports of
      epistasis are not robustly supported in the published literature, our results
      suggest that at least some of these reports may have been true-positive examples
      of epistasis. In general, improvements in empirical studies of epistasis are
      called for, in order to better understand the importance of this phenomenon in
      human disease.

PMID- 25998950
TI  - Correction: Axl Kinase as a Key Target for Oncology: Focus on Small Molecule
      Inhibitors.

PMID- 25998949
TI  - Characterization of amoxicillin- and clavulanic acid-specific T cells in patients
      with amoxicillin-clavulanate-induced liver injury.
AB  - Drug-induced liver injury (DILI) frequently has a delayed onset with several
      human leukocyte antigen (HLA) genotypes affecting susceptibility, indicating a
      potential role for the adaptive immune system in the disease. The aim of this
      study was to investigate whether drug-responsive T lymphocytes are detectable in
      patients who developed DILI with the combination, antimicrobial amoxicillin
      clavulanate. Lymphocytes from 6 of 7 patients were found to proliferate and/or
      secrete interferon-gamma (IFN-gamma) when cultured with amoxicillin and/or
      clavulanic acid. Amoxicillin (n = 105) and clavulanic acid (n = 16) responsive
      CD4(+) and CD8(+) T-cell clones expressing CCR, chemokine (C-C motif) receptor 4,
      CCR9, and chemokine (C-X-C motif) receptor 3 were generated from patients with
      and without HLA risk alleles; no cross-reactivity was observed between the two
      drug antigens. Amoxicillin clones were found to secrete a heterogeneous panel of
      mediators, including IFN-gamma, interleukin-22 and cytolytic molecules. In
      contrast, cytokine secretion by the clavulanic acid clones was more restricted.
      CD4(+) and CD8(+) clones were major histocompatability complex class II and I
      restricted, respectively, with the drug antigen being presented to CD4(+) clones
      in the context of HLA-DR molecules. Several pieces of evidence indicate that the
      clones were activated by a hapten mechanism: First, professional antigen
      presenting cells (APCs) were required for optimal activation; second, pulsing
      APCs for 4-16 hours activated the clones; and third, inhibition of processing
      abrogated the proliferative response and cytokine release. CONCLUSION: Both
      amoxicillin- and clavulanic acid-specific T cells participate in the liver injury
      that develops in certain patients exposed to amoxicillin-clavulanate.

PMID- 25998952
TI  - Functional interrelationship of brain aging and delirium.
AB  - Theories on the development of delirium are complementary rather than competing
      and they may relate to each other. Here, we highlight that similar alterations in
      functional brain connectivity underlie both the observed age-related deficits and
      episodes of delirium. The default mode network (DMN) is a group of brain regions
      showing a greater level of activity at rest than during attention-based tasks.
      These regions include the posteromedial-anteromedial cortices and temporoparietal
      junctions. Evidence suggests that awareness is subserved through higher order
      neurons associated with the DMN. By using functional MRI disruption of DMN,
      connectivity and weaker task-induced deactivations of these regions are observed
      both in age-related cognitive impairment and during episodes of delirium. We can
      assume that an acute up-regulation of inhibitory tone within the brain acts to
      further disrupt network connectivity in vulnerable patients, who are predisposed
      by a reduced baseline connectivity, and triggers the delirium. 

PMID- 25998951
TI  - Synapsin IIb as a functional marker of submissive behavior.
AB  - Dominance and submissiveness are important functional elements of the social
      hierarchy. By employing selective breeding based on a social interaction test, we
      developed mice with strong and stable, inheritable features of dominance and
      submissiveness. In order to identify candidate genes responsible for dominant and
      submissive behavior, we applied transcriptomic and proteomic studies supported by
      molecular, behavioral and pharmacological approaches. We clearly show here that
      the expression of Synapsin II isoform b (Syn IIb) is constitutively upregulated
      in the hippocampus and striatum of submissive mice in comparison to their
      dominant and wild type counterparts. Moreover, the reduction of submissive
      behavior achieved after mating and delivery was accompanied by a marked reduction
      of Syn IIb expression. Since submissiveness has been shown to be associated with
      depressive-like behavior, we applied acute SSRI (Paroxetine) treatment to reduce
      submissiveness in studied mice. We found that reduction of submissive behavior
      evoked by Paroxetine was paired with significantly decreased Syn IIb expression.
      In conclusion, our findings indicate that submissiveness, known to be an
      important element of depressive-like behavioral abnormalities, is strongly linked
      with changes in Syn IIb expression. 

PMID- 25998953
TI  - Do older adults with higher daily ambulatory activity have lower central blood
      pressure?
AB  - BACKGROUND AND AIMS: We aimed to test the hypothesis that central blood pressure
      (BP) would be lower in healthy older adults with greater daily ambulatory
      activity. METHODS: Forty-three (24 women, 19 men) older adults wore a triaxial
      accelerometer at the hip for 1 week. The volume of ambulatory activity was
      estimated by average steps per day. As a proxy of intensity of ambulatory
      activity, 1-min peak step accumulation, or the maximum number of steps taken
      within a minute was averaged from each day. Participants were considered "active"
      if they had >7500 steps per day or >105 steps per min. Radial arterial tonometry
      was used to estimate central (aortic) BP from pulse wave analysis. RESULTS: After
      adjusting for age and sex, adults with higher steps per day (n = 18) tended to
      have lower central pulse pressure (p = 0.08). Interestingly, adults with higher
      peak step accumulation (n = 25) had significantly lower central pulse pressure
      (40.4 +/- 1.6 vs. 46.8 +/- 2.0 mmHg; p = 0.02) after adjusting for age and sex.
      Stepwise regression including age, sex, body mass index, and peak step
      accumulation found body mass index to be the strongest predictor of central
      systolic BP [beta = 0.42, 95 % CI (0.13, 0.70), p = 0.004] while peak step
      accumulation was the strongest predictor of central pulse pressure [beta = -0.31,
      95 % CI (-0.01, -0.60), p = 0.043]. CONCLUSIONS: These results find older adults
      with an "active" daily walking pattern, particularly having a higher number of
      maximal steps in a minute, have lower central pulse pressure than older adults
      with lower daily ambulatory activity.

PMID- 25998954
TI  - The effects of asymmetric hearing on bilateral brainstem function: findings in
      children with bimodal (electric and acoustic) hearing.
AB  - As implantation criteria are broadening to include children with asymmetric
      hearing loss, it is important to determine the degree of residual hearing needed
      to protect the bilateral auditory pathways for binaural hearing and whether there
      is a sensitive period in development for implantation in these children. We have
      been studying these questions in a growing cohort of children. In the present
      study, auditory brainstem responses were recorded in 21 children who had 2.2 +/-
      2.2 years of bimodal hearing. Responses were evoked by 11-Hz acoustic clicks
      presented to the non-implanted ear and with biphasic electric pulses presented to
      the implanted ear. Twelve of these children also completed a behavioural task in
      which they were asked to which side of their heads bilaterally presented
      clicks/pulses that varied in interaural level or timing lateralized. All children
      experienced a delay in the non-implanted ear that resulted in 2.0 +/- 0.35 ms
      longer peak latencies. These were further prolonged in 7 children as measured by
      longer interwave latencies from this ear than from the implanted ear. Despite
      large asymmetries in timing of brainstem activity between the two ears, all
      children perceived changes in interaural level differences. They were unable to
      detect differences in interaural timing cues. Symmetric brainstem function
      suggests bilateral development was preserved in some children. Future work will
      explore whether these children have better potential for developing binaural
      hearing using bimodal input.

PMID- 25998955
TI  - Localization of the Patency Capsule by Abdominal Tomosynthesis.
AB  - BACKGROUND/AIMS: A patency capsule (PC) is used to assess intestinal patency in
      patients with known or suspected stricture, but PC localization by plain
      abdominal X-ray (AXR) is difficult in those patients in whom the PC is not
      detected in the feces. Tomosynthesis is a promising, cost-effective, and low
      radiation digital tomographic technique. This prospective study evaluated its use
      for PC localization in the intestinal tract. METHODS: The study subjects were 49
      patients in whom the PC was not detected in the feces and was identified intra
      abdominally on AXR films. PC localization in the small or large intestines by AXR
      alone or by tomosynthesis with AXR was compared with abdominal computed
      tomography (CT), which is the gold standard. RESULTS: The PC was judged in the
      large and small intestines in 22 and 27 patients by AXR alone versus 34 and 15
      patients, respectively, by tomosynthesis combined with AXR. The sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      for PC detection by AXR alone were 52.9, 53.3, 56.2, 50.0, and 53.1%,
      respectively. The same parameters were 100, 100, 100, 100, and 100%,
      respectively, for tomosynthesis with AXR, which were identical to those of CT.
      CONCLUSIONS: Tomosynthesis with AXR is superior to AXR alone, though similar to
      CT, with respect to localization of the PC.

PMID- 25998957
TI  - A single dual-stream framework for syntactic computations in music and language.
AB  - This study is the first to compare in the same subjects the specific spatial
      distribution and the functional and anatomical connectivity of the neuronal
      resources that activate and integrate syntactic representations during music and
      language processing. Combining functional magnetic resonance imaging with
      functional connectivity and diffusion tensor imaging-based probabilistic
      tractography, we examined the brain network involved in the recognition and
      integration of words and chords that were not hierarchically related to the
      preceding syntax; that is, those deviating from the universal principles of
      grammar and tonal relatedness. This kind of syntactic processing in both domains
      was found to rely on a shared network in the left hemisphere centered on the
      inferior part of the inferior frontal gyrus (IFG), including pars opercularis and
      pars triangularis, and on dorsal and ventral long association tracts connecting
      this brain area with temporo-parietal regions. Language processing utilized some
      adjacent left hemispheric IFG and middle temporal regions more than music
      processing, and music processing also involved right hemisphere regions not
      activated in language processing. Our data indicate that a dual-stream system
      with dorsal and ventral long association tracts centered on a functionally and
      structurally highly differentiated left IFG is pivotal for domain-general
      syntactic competence over a broad range of elements including words and chords. 

PMID- 25998959
TI  - Back to the Future?

PMID- 25998958
TI  - Interleukin-10 gene transfer into insulin-producing beta cells protects against
      diabetes in non-obese diabetic mice.
AB  - Type 1 diabetes is an autoimmune disorder, which occurs due to beta cell damage.
      Interleukin (IL)-10, a pleotropic cytokine, has been reported to have anti
      inflammatory, immunosuppressive and immunostimulatory properties. Administration
      of IL-10 is known to prevent autoimmune diabetes in non-obese diabetic (NOD)
      mice. However, the mechanism of IL-10-induced protection in NOD mice requires
      further investigation. The aim of the present study was to evaluate the
      protective effect of transgenic IL-10 expression in pancreatic beta cells against
      autoimmune damage in NOD mice and to elucidate its mechanism of action. Female
      NOD mice (9 weeks old) were intraperitoneally injected with an adenovirus
      carrying either IL-10 (Adv-IL-10) or green fluorescent protein (Adv-GFP). Blood
      glucose was monitored weekly and the expression of IL-10 was evaluated using
      reverse transcription quantitative polymerase chain reaction. IL-10 and
      interferon (IFN)-gamma expression levels in serum and splenocytes were analyzed.
      CD4+CD25+FoxP3+ T regulatory (Treg) cells were determined by flow cytometry.
      Apoptosis of pancreatic beta cells was determined using a terminal
      deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay
      and expression levels of Fas and caspase-3 were estimated by immunohistochemistry
      analysis. The results revealed that mice treated with IL-10 showed less severe
      insulitis and a lower incidence of diabetes compared with the saline control and
      Adv-GFP groups. In addition, compared with the control group, IFN-gamma levels
      were decreased in sera and splenocytes, while IL-10 expression was increased in
      sera only. The number of CD4+CD25+FoxP3+ Treg cells was increased in IL-10
      injected mice. Furthermore, the expression levels of Fas and caspase-3 were
      decreased in IL-10-injected mice compared with that of GFP-injected and control
      mice, which was concomitant with a reduction in beta cell apoptosis. In
      conclusion, the present study demonstrated that IL-10 gene transfer reduced the
      expression of the inflammatory cytokines, attenuated pancreatic insulitis and
      inhibited beta cell apoptosis. This therefore indicated that IL-10 reduced the
      incidence of diabetes in female NOD mice.

PMID- 25998956
TI  - Meta-analytic connectivity and behavioral parcellation of the human cerebellum.
AB  - The cerebellum historically has been thought to mediate motor and sensory signals
      between the body and cerebral cortex, yet cerebellar lesions are also associated
      with altered cognitive behavioral performance. Neuroimaging evidence indicates
      that the cerebellum contributes to a wide range of cognitive, perceptual, and
      motor functions. Here, we used the BrainMap database to investigate whole-brainco
      activation patterns between cerebellar structures and regions of the cerebral
      cortex, as well as associations with behavioral tasks. Hierarchical clustering
      was performed to meta-analytically identify cerebellar structures with similar
      cortical co-activation, and independently, with similar correlations to specific
      behavioral tasks. Strong correspondences were observed in these separate but
      parallel analyses of meta-analytic connectivity and behavioral metadata. We
      recovered differential zones of cerebellar co-activation that are reflected
      across the literature. Furthermore, the behaviors and tasks associated with the
      different cerebellar zones provide insight into the specialized function of the
      cerebellum, relating to high-order cognition, emotion, perception, interoception,
      and action. Taken together, these task-basedmeta-analytic results implicate
      distinct zones of the cerebellum as critically involved in the monitoring and
      mediation of psychological responses to internal and external stimuli. 

PMID- 25998960
TI  - Evaluating emergency nurse practitioner service effectiveness on achieving timely
      analgesia: a pragmatic randomized controlled trial.
AB  - OBJECTIVES: The rapid uptake of nurse practitioner (NP) services in Australia has
      outpaced evaluation of this service model. A randomized controlled trial was
      conducted to compare the effectiveness of NP service versus standard medical care
      in the emergency department (ED) of a major referral hospital in Australia.
      METHODS: Patients presenting with pain were randomly assigned to receive either
      standard ED medical care or NP care. Primary investigators were blinded to
      treatment allocation for data analyses. The primary outcome measure was the
      proportion of patients receiving analgesia within 30 minutes from being seen by
      care group. Secondary outcome measures were time to analgesia from presentation
      and documentation of and changes in pain scores. RESULTS: There were 260 patients
      randomized; 128 received standard care (medical practitioner led), and 130
      received NP care. Two patients needed to be excluded due to incomplete consent
      forms. The proportion of patients who received analgesia within 30 minutes from
      being seen was 49.2% (n = 64) in the NP group and 29.7% (n = 38) in the standard
      group, a difference of 19.5% (95% confidence interval [CI] = 7.9% to 31.2%; p =
      0.001). Of 165 patients who received analgesia, 64 (84.2%) received analgesia
      within 30 minutes in the NP group compared to 38 (42.7%) in the standard care
      group, a difference in proportions of 41.5% (95% CI = 28.3% to 54.7%; p < 0.001).
      The mean (+/-SD) time from being seen to analgesia was 25.4 (+/-39.2) minutes for
      NP care and 43.0 (+/-35.5) minutes for standard care, a difference of 17.6
      minutes (95% CI = 6.1 to 29.1 minutes; p = 0.003). There was a difference in the
      median change in pain score of 0.5 between care groups, but this was not
      statistically significant (p = 0.13). CONCLUSIONS: Nurse practitioner service
      effectiveness was demonstrated through superior performance in achieving timely
      analgesia for ED patients.

PMID- 25998962
TI  - T CELLS: Role reversal.

PMID- 25998961
TI  - Lymph node fibroblastic reticular cells  in health and disease.
AB  - Over the past decade, a series of discoveries relating to fibroblastic reticular
      cells (FRCs) - immunologically specialized myofibroblasts found in lymphoid
      tissue - has promoted these cells from benign bystanders to major players in the
      immune response. In this Review, we focus on recent advances regarding the
      immunobiology of lymph node-derived FRCs, presenting an updated view of crucial
      checkpoints during their development and their dynamic control of lymph node
      expansion and contraction during infection. We highlight the robust effects of
      FRCs on systemic B cell and T cell responses, and we present an emerging view of
      FRCs as drivers of pathology following acute and chronic viral infections.
      Lastly, we review emerging therapeutic advances that harness the immunoregulatory
      properties of FRCs.

PMID- 25998964
TI  - Interventional cardiology: in search of the balance between ischaemia and
      bleeding.

PMID- 25998965
TI  - New perspectives: transcatheter aortic valve implantation in the year 2020.

PMID- 25998966
TI  - Safety of Cryo-Transbronchial Biopsy in Diffuse Lung Diseases: Analysis of Three
      Hundred Cases.
AB  - BACKGROUND: Transbronchial biopsy (TBB) which is performed with metal forceps
      (forceps TBB) has been accepted as a useful technique in establishing diagnoses
      of diffuse lung diseases (DLDs). The use of cryoprobes to obtain alveolar tissue
      (cryo-TBB) is a new method which is currently used by our institute as well as
      others with excellent results. OBJECTIVES: To assess the safety of cryo-TBB
      compared with conventional forceps TBB. METHODS: We performed a retrospective
      data evaluation of 300 consecutive patients who underwent cryo-TBB between
      January 2012 and April 2014 and compared them with historical cases treated with
      forceps TBB between 2010 and 2012. The results of both diagnostic modalities were
      compared based on pathological reports. The major complications (significant
      bleeding and pneumothorax) were compared, along with postprocedural
      hospitalization. RESULTS: Pneumothorax was observed in 15 cases (4.95%) treated
      with cryo-TBB versus 9 cases (3.15%) treated with forceps TBB, with no
      significant difference (p = 0.303). The insertion of a chest tube was necessary
      in 6 (2%) and 4 (1.3%) of the cases having undergone cryo-TBB or forceps TBB,
      respectively (p = 0.8). In the cryo-TBB group, bleeding was encountered in 16
      cases (5.2%), and it occurred in 13 cases (4.5%) of the forceps TBB group, with
      no significant difference in rates (p = 0.706). Also, there was no significant
      difference in hospital admission rates between the groups [cryo-TBB: 10 (3.3%);
      forceps TBB: 4 (1.44%); p = 0.181]. The safety profile of cryo- and forceps TBB
      remained the same even when stratified according to indications for TBB, i.e.
      immunocompromised hosts, patients after lung transplantation and those with DLDs.
      CONCLUSION: In patients with DLDs, cryo-TBB is as safe as forceps TBB.

PMID- 25998967
TI  - Occurrence of bilaterally independent epileptic spasms after a corpus callosotomy
      in West syndrome.
AB  - We report a patient with intractable West syndrome whose epileptic spasms (ESs)
      were initially bilaterally synchronous, as is typical; after a complete corpus
      callosotomy, however, bilaterally independent ESs originated in either
      hemisphere. Activity of probable cortical origin associated with ESs was detected
      by observing ictal gamma oscillations. Brain MRI revealed no structural
      abnormality before surgery. This case suggests that ESs with a hemispheric origin
      may appear generalized because of synchronizing effects in the corpus callosum in
      some patients. 

PMID- 25998968
TI  - Phenytoin toxicity in two-month-old Thai infant with CYP2C9 gene polymorphism--A
      case report.
AB  - Phenytoin is one of the most well established and most effective antiepileptic
      medications for the treatment of focal seizures. In our clinical practice, it has
      proven difficult to maintain therapeutic phenytoin levels in infants less than
      three months of age. Incidence of phenytoin toxicity in infants is very rare. The
      cytochrome P450 super family plays an important role in phenytoin metabolism,
      especially CYP2C9 and CYP2C19. In this case report, we profiled a two-month-old
      Thai infant who developed phenytoin toxicity resulting from CYP2C9 gene
      polymorphism. 

PMID- 25998963
TI  - Perforin and granzymes: function,  dysfunction and human pathology.
AB  - A defining property of cytotoxic lymphocytes is their expression and regulated
      secretion of potent toxins, including the pore-forming protein perforin and
      serine protease granzymes. Until recently, mechanisms of pore formation and
      granzyme transfer into the target cell were poorly understood, but advances in
      structural and cellular biology have now begun to unravel how synergy between
      perforin and granzymes brings about target cell death. These and other advances
      are demonstrating the surprisingly broad pathophysiological roles of the perforin
      granzyme pathway, and this has important implications for understanding immune
      homeostasis and for developing immunotherapies for cancer and other diseases. In
      particular, we are beginning to define and understand a range of human diseases
      that are associated with a failure to deliver active perforin to target cells. In
      this Review, we discuss the current understanding of the structural, cellular and
      clinical aspects of perforin and granzyme biology.

PMID- 25998969
TI  - The alignment of agricultural and nature conservation policies in the European
      Union.
AB  - Europe is a region of relatively high population density and productive
      agriculture subject to substantial government intervention under the Common
      Agricultural Policy (CAP). Many habitats and species of high conservation
      interest have been created by the maintenance of agricultural practices over long
      periods. These practices are often no longer profitable, and nature conservation
      initiatives require government support to cover the cost for them to be
      continued. The CAP has been reformed both to reduce production of agricultural
      commodities at costs in excess of world prices and to establish incentives for
      landholders to adopt voluntary conservation measures. A separate nature
      conservation policy has established an extensive series of protected sites
      (Natura 2000) that has, as yet, failed to halt the loss of biodiversity.
      Additional broader scale approaches have been advocated for conservation in the
      wider landscape matrix, including the alignment of agricultural and nature
      conservation policies, which remains a challenge. Possibilities for alignment
      include further shifting of funds from general support for farmers toward
      targeted payments for biodiversity goals at larger scales and adoption of an
      ecosystem approach. The European response to the competing demands for land
      resources may offer lessons globally as demands on rural land increase. 

PMID- 25998970
TI  - Radioresistant Sf9 insect cells display efficient antioxidant defence against
      high dose gamma-radiation.
AB  - PURPOSE: To investigate the effect of gamma radiation-induced alterations in
      antioxidant defence of radioresistant Sf9 insect cells. MATERIALS AND METHODS:
      Sf9 cells were irradiated at doses ranging from 0.5-200 Gy. Lipid peroxidation
      and protein carbonylation levels were observed at 4 h post-exposure along with
      reduced glutathione/oxidized glutathione (GSH/GSSG) profile as well as specific
      activities of redox active enzymes superoxide dismutase (SOD), catalase,
      ascorbate peroxidase (APOx), and glutathione reductase (GR). Human brain
      malignant glioma (BMG-1) cells were used for comparing radiation response of
      mammalian cells. RESULTS: Sf9 cells displayed significantly less radiation
      induced reactive oxygen/nitrogen species (ROS/RNS) generation, protein
      carbonylation and growth inhibition as compared to mammalian cells. Sf9 cells
      have higher basal APOx (~4-fold), catalase (~1.7-fold), SOD (~1.3-fold) activity
      and GSH level (~2.2-fold) compared to mammalian cells. A radiation dose-dependent
      increase in SOD, Catalase and APOx activity was found in Sf9 cells at least up to
      100 Gy dose, while maximum activity in mammalian cells was achieved by 10 Gy.
      CONCLUSION: The present study suggests that Lepidopteran insect cells carry a
      stronger antioxidant system that protects against radiation-induced
      macromolecular damage, growth inhibition and cell death.

PMID- 25998971
TI  - The Effectiveness of Family Interventions in Preventing Adolescent Illicit Drug
      Use: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
AB  - In order to quantify the effectiveness of family interventions in preventing and
      reducing adolescent illicit drug use, we conducted a systematic review and meta
      analysis of randomized controlled trials. We searched the Cochrane Database of
      Systematic Reviews, Educational Research Information Centre (ERIC), MEDLINE,
      Embase, and PsycINFO for studies published between 1995 and 2013. Results were
      described separately for different outcomes (marijuana vs. other illicit drugs)
      and intervention types (universal, selective, and indicated prevention). Meta
      analyses were performed when data were sufficient (e.g., marijuana and other
      illicit drug initiation in universal samples), using random effect models.
      Otherwise, we provided narrative reviews (e.g., regarding selective and indicated
      prevention). Thirty-nine papers describing 22 RCTs were eligible for inclusion.
      Universal family interventions targeting parent-child dyads are likely to be
      effective in preventing (OR 0.72; 95 % CI 0.56, 0.94) and reducing adolescent
      marijuana use, but not in preventing other illicit drugs (OR 0.90; 95 % CI 0.60,
      1.34). Among high-risk groups, there is no clear evidence for the effectiveness
      of family interventions in preventing and reducing illicit drug use and drug
      disorders. The three small RCTs among substance-(ab)using adolescents gave some
      indication that programs might reduce the frequency of illicit drug use. Family
      interventions targeting parent-child dyads are likely to be effective in
      preventing and reducing adolescent marijuana use in general populations, but no
      evidence for other illicit drug use was found. We underline the need to
      strengthen the evidence base with more trials, especially among at-risk
      populations. 

PMID- 25998972
TI  - [Changing paradigm in the management of inflammatory bowel disease].
AB  - Inflammatory bowel disease (IBD) is a chronic progressive idiopathic inflammatory
      disorder that involves the digestive tract from the mouth to the anus. Over the
      past decades, many therapeutic strategies have been developed to manage IBD, but
      therapeutic strategies based only on relief of clinical symptoms have not changed
      the natural history of this disease entity. This underlines the importance of
      understanding the natural history of IBD itself. When we look at the natural
      history of Crohn's disease (CD), it first begins with inflammation of the
      intestinal mucosa and this inflammatory reaction proceeds to stenosing or
      penetrating reaction if not adequately controlled. However, it takes a
      considerable amount of time before mucosal inflammation proceeds to stenosis of
      the intestinal lumen or penetration into the adjacent bowel. Therefore, it can be
      expected that if proper care is given during that period, progression of CD to
      such a complicated disease could be prevented. Even though the concept of mucosal
      healing was introduced in the early 1990 s, no correlation could be observed
      between healing of mucosal lesions and relief of clinical symptoms. However, the
      introduction of biologic agents targeting tumor necrosis factor has changed the
      way to treat IBD that is refractory to standard medications and has allowed us to
      aim for a new therapeutic goal, 'deep remission'. Further advances in biologic
      agents have provided highly effective treatments for IBD, making deep remission a
      realistic goal. Whether IBD patients may benefit by experiencing a 'deep'
      remission beyond the control of clinical symptoms need to be evaluated in further
      investigation. Nevertheless, it can be anticipated that attaining deep remission
      might ultimately have an impact on important outcomes such as the need for
      surgery and the quality of life.

PMID- 25998973
TI  - Long-term Outcomes of Laparoscopic versus Open Surgery for Rectal Cancer: A
      Single-center Retrospective Analysis.
AB  - BACKGROUND/AIMS: Laparoscopic surgery has been proven to be an effective
      alternative to open surgery in patients with colon cancer. However, data on
      laparoscopic surgery in patients with rectal cancer are insufficient. The aim of
      this study was to compare the long-term outcomes of laparoscopic and open surgery
      in patients with rectal cancer. METHODS: A total of 307 patients with rectal
      cancer who were treated by open and laparoscopic curative resection at Kosin
      University Gospel Hospital (Busan, Korea) between January 2002 and December 2011
      were reviewed retrospectively. RESULTS: Regarding treatment, 176 patients
      underwent an open procedure and 131 patients underwent a laparoscopic procedure.
      The local recurrence rate after laparoscopic resection was 2.3%, compared with
      5.7% after open resection (p = 0.088). Distant metastases occurred in 6.9% of the
      laparoscopic surgery group, compared with 24.4% in the open surgery group (p <
      0.001). In univariate analysis, age (>= 75 years vs. <= 60 years), preoperative
      staging, surgical approach (open vs. laparoscopic), elevated initial CEA level,
      elevated follow-up CEA level, number of positive lymph nodes, and postoperative
      chemotherapy affected overall survival and disease free survival. However, in
      multivariate analysis, the surgical approach apparently did not affect long-term
      oncologic outcome. CONCLUSIONS: In this study, long-term outcomes after
      laparoscopic surgery for rectal cancer were not inferior to those after open
      surgery. Therefore, laparoscopic surgery would be an alternative operative tool
      to open resection for rectal cancer, although further investigation is needed.

PMID- 25998974
TI  - The effect of urocortin 1 on motility in isolated, vascularly perfused rat colon.
AB  - BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide,
      increases colonic motility under stressful conditions. We investigated the effect
      of urocortin 1 on colonic motility using an experimental model with isolated rat
      colon in which the blood flow and intestinal nerves were preserved. Furthermore,
      we assessed whether this effect was mediated by adrenergic or cholinergic nerves.
      METHODS: Colonic motility was measured in the proximal and distal parts of
      resected rat colon. The colon resected from the peritoneum was stabilized, and
      then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood
      vessel. Motility index was measured in the last 5 min of the 15 min
      administration of urocortin 1 and expressed as percentage change from baseline.
      Subsequently, the change in motility was measured by perfusing urocortin 1 in
      colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or
      tetrodotoxin. RESULTS: At concentrations of 13.8, 138, 277, and 1,388 pM,
      urocortin 1 increased the motility of proximal colon (20.4 +/- 7.2%,48.4 +/-
      20.9%, 67.0 +/- 25.8%, and 64.2 +/- 20.9%, respectively) and the motility of
      distal colon (3.3 +/- 3.3%, 7.8 +/- 7.8%, 71.1 +/- 28.6%,and 87.4 +/- 32.5%,
      respectively). The motility induced by urocortin 1 was significantly decreased by
      atropine to 2.4 +/- 2.4% in proximal colon and 3.4 +/- 3.4% in distal colon (p <?
      0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did
      not inhibit motility. CONCLUSIONS: Urocortin 1 increased colonic motility and it
      is considered that this effect was directly mediated by local muscarinic
      cholinergic receptors.

PMID- 25998975
TI  - [Conservative management of adult small bowel intussusception detected at
      abdominal computed tomography].
AB  - BACKGROUND/AIMS: The incidence of adult small bowel intussusception detected at
      CT has increased with advanced imaging techniques and universal utilization of CT
      scan. We aimed to identify factors that could predict the necessity of surgical
      intervention in adult patients with small bowel intussusception detected at CT
      during the past decade. METHODS: There were 39 cases of adult small-bowel
      intussusception detected at CT from January 2004 to June 2014. The data on
      clinical factors, radiological factors and outcomes were collected by
      retrospectively reviewing all available medical records. Patients were classified
      as surgical group and conservative group according to the outcome. Association
      between predictive factors and outcome was assessed by Fisher's exact test and
      logistic regression models. RESULTS: Among a total of 39 patients, there were 32
      patients (82%) in the conservative group and 7 patients (18%) in the surgical
      group. Spontaneous reduction was confirmed at short-term follow-up studies
      (abdominal ultrasonography [n=14], single contrast small bowel series [n=14], CT
      [n=4]) in the conservative group. No recurrence occurred during the median follow
      up period of 14.1 months (range, 0-67.5 months). Patients in the surgical group
      had significantly higher white blood cell (WBC) counts (OR 1.001, p=0.048), more
      frequent obstruction (n=4 vs. n=4, p=0.022) or leading point (n=5 vs. n=0,
      p<0.001) and longer intussuception length (OR 1.929, p=0.032). CONCLUSIONS:
      Factors associated with the necessity to resort to surgical intervention in
      adults with small bowel intussusceptions were higher WBC counts, presence of
      obstruction or leading point, and longer intussuception length. Conservative
      management can be considered with short-term follow-up for those without these
      predictive factors.

PMID- 25998976
TI  - Does Endoscopic Sphincterotomy and/or Cholecystectomy Reduce Recurrence Rate of
      Acute Biliary Pancreatitis?
AB  - BACKGROUND/AIMS: Practice guidelines from international societies have
      recommended cholecystectomy during the same hospitalization for acute biliary
      pancreatitis (ABP). The aim of this study is to investigate the question of
      whether endoscopic sphincterotomy (EST) and/or cholecystectomy during the same
      hospitalization can reduce the recurrence rate of ABP. METHODS: A total of 119
      patients with ABP admitted to our institution between May 2005 and May 2010 who
      had complete follow-up data until May 2012 were enrolled. RESULTS: No significant
      differences in initial CT severity index and Charlson comorbidity index were
      observed between EST (n = 64) and non-EST group (n = 55) and among subgroups
      classified according to interventions performed. In Kaplan-Meier analyses,
      significantly higher recurrence rates of ABP were observed in the non-EST group
      compared to the EST group (p <? 0.01), and in the conservative treatment group
      compared to other intervention groups (p <? 0.01). The frequency of complications
      from ABP was significantly higher in the conservative treatment group (35.7%) and
      lowest in the EST plus cholecystectomy group (5.0%, p = 0.008). In multivariate
      analysis, conservative treatment without EST and/or cholecystectomy, and non-EST
      group were independent risk factors for recurrence after the initial attack of
      ABP. CONCLUSIONS: ERCP with EST and cholecystectomy during the index admission is
      associated with reduced recurrence rates of ABP.

PMID- 25998977
TI  - [A Case of Paradoxical Reaction Development during Antituberculosis Therapy].
AB  - Paradoxical reaction during antituberculosis therapy is defined as aggravation of
      preexisting tuberculous lesions or the development of new lesions. A 24-year-old
      female college student diagnosed with abdominal and pulmonary tuberculosis
      presented with fever and abdominal pain after having been treated with
      antituberculosis agents for 4 months. Tuberculous mesenteric lymphadenitis was
      suspected on abdominal CT scan and enlarged necrotic abscess was also present.
      These findings were considered to be due to paradoxical reaction rather than
      treatment failure during antituberculosis treatment. Although laparoscopic bowel
      adhesiolysis and abscess drainage were performed, high fever and severe abdominal
      pain did not improve. However, the patient eventually made a completely recovery
      after corticosteroid therapy combined with antituberculosis agents. Herein, we
      report a case of paradoxical reaction which developed in a patient with abdominal
      and pulmonary tuberculosis during antituberculosis therapy.

PMID- 25998978
TI  - Spontaneous neoplastic remission of hepatocellular carcinoma.
AB  - We report on a case of a 57-year-old male who underwent a curative resection for
      hepatocellular carcinoma (HCC) with histological confirmation of a spontaneously
      necrotized tumor. Initial serum AFP level was 4,778 ng/mL. A 3.7 cm hyperechoic
      mass in segment 6 of the liver was observed on ultrasonography and dynamic
      contrast-enhanced liver MRI showed a 3.7 * 3.1 cm sized HCC. He was scheduled to
      undergo curative surgical resection under the clinical diagnosis of an early
      stage HCC (Barcelona Clinic Liver Cancer stage A). Without treatment, the serum
      AFP level declined rapidly to 50 ng/mL over five weeks. He underwent curative
      wedge resection of segment 6 of the liver. Histology revealed complete necrosis
      of the mass rimmed by inflamed fibrous capsule on a background of HBV-related
      cirrhosis with infiltration of lymphoplasma cells. Exact pathophysiology
      underlying this event is unknown. Among the proposed mechanisms of spontaneous
      neoplastic remission of HCC, circulatory disturbance and activation of host
      immune response offer the most scientific explanation for the complete histologic
      necrosis of HCC in the resected mass seen in our patient.

PMID- 25998979
TI  - [Portal vein thrombosis with sepsis caused by inflammation at colonic stent
      insertion site].
AB  - Portal vein thrombosis is an uncommon but an important cause of portal
      hypertension. The most common etiological factors of portal vein thrombosis are
      liver cirrhosis and malignancy. Albeit rare, portal vein thrombosis can also
      occur in the presence of local infection and inflammation such as pancreatitis or
      cholecystitis. A 52-year-old male was admitted because of general weakness and
      poor oral intake. He had an operation for colon cancer 18 months ago. However,
      colonic stent had to be inserted afterwards because stricture developed at
      anastomosis site. Computed tomography taken at admission revealed portal vein
      thrombosis and inflammation at colonic stent insertion site. Blood culture was
      positive for Escherichia coli. After antibiotic therapy, portal vein thrombosis
      resolved. Herein, we report a case of portal vein thrombosis with sepsis caused
      by inflammation at colonic stent insertion site which was successfully treated
      with antibiotics. 

PMID- 25998980
TI  - A case of multiple hypervascular hyperplastic liver nodules in a patient with no
      history of alcohol abuse or chronic liver diseases.
AB  - Up-to-date imaging modalities such as three-dimensional dynamic contrast-enhanced
      CT (3D CT) and MRI may contribute to detection of hypervascular nodules in the
      liver. Nevertheless, distinguishing a malignancy such as hepatocellular carcinoma
      from benign hypervascular hyperplastic nodules (HHN) based on the radiological
      findings is sometimes difficult. Multiple incidental liver masses were detected
      via abdominal ultrasonography (US) in a 65-year-old male patient. He had no
      history of alcohol intake and no remarkable past medical history or relevant
      family history, and his physical examination results and laboratory findings were
      normal. 3D CT and MRI showed numerous enhanced nodules with hypervascularity
      during the arterial phase. After US guided liver biopsy, the pathological
      diagnosis was HHN. To date, several cases of HHN have been reported in patients
      with chronic alcoholic liver disease or cirrhosis. Herein, we report on a case of
      HHN in a patient with no history of alcoholic liver disease or cirrhosis. 

PMID- 25998981
TI  - Role of Nox inhibitors plumbagin, ML090 and gp91ds-tat peptide on homocysteine
      thiolactone induced blood vessel dysfunction.
AB  - Antioxidants have not reduced the burden of cardiovascular disease, and current
      evidence suggests a beneficial role of oxidative stress, via NADPH oxidase (Nox)
      upregulation, in endothelial function. Homocysteine thiolactone (HcyT) induces
      blood vessel dysfunction and this correlates with increased vascular oxidative
      stress. This study aimed to determine if pharmacological inhibition of Nox could
      impair HcyT induced blood vessel dysfunction. Abdominal aorta were excised from
      New Zealand White rabbits (n = 6), cut into rings and sequentially mounted in
      organ baths. Rings were preincubated with 0.55 MUmol/L homocysteine thiolactone
      for 1 h, or combinations of putative Nox inhibitors (plumbagin for Nox4, gp91ds
      tat for Nox2, and ML090 for Nox1), 30 min prior to the addition of HcyT, followed
      by a dose response curve to acetylcholine on phenylephrine preconstricted rings.
      Plumbagin, ML090 + gp91ds-tat and HcyT reduced responses to acetylcholine, and
      Plumbagin + Hcyt caused constriction to acetylcholine, which was normalised to
      plumbagin by ML090. Plumbagin + ML090 or plumbagin + gp91ds-tat completely
      impaired the effect of acetylcholine. ML090 inhibited the effect of HcyT on
      reduced response to acetylcholine, whereas gp91ds-tat had no effect. This study
      concludes that inhibition of Nox1 prevents, whereas inhibition of Nox4 worsens,
      acetylcholine induced blood vessel relaxation caused by HcyT, while Nox2
      inhibition has no effect. However combinations of Nox inhibitors worsen
      acetylcholine induced blood vessel relaxation. These results suggest that there
      is cross-talk between Nox isoforms during physiological and pathophysiological
      processes.

PMID- 25998982
TI  - Improved performance and immunological responses as the result of dietary
      genistein supplementation of broiler chicks.
AB  - The present study aimed to investigate the effect of supplemental genistein (an
      isoflavonoid) on performance, lymphoid organs' development, and cellular and
      humoral immune responses in broiler chicks. A total of 675-day-old male broiler
      chicks (Ross 308) were randomly assigned to the five replicate pens (15 chicks
      each) of nine experimental diets. Dietary treatments included a negative (not
      supplemented) control diet, two positive control groups (virginiamycin or zinc
      bacitracin, 20 mg/kg), and diets containing 10, 20, 40, 80, 160 and 320 mg/kg of
      genistein. The cutaneous basophil hypersensivity (CBH) test was measured at day
      10 of age after toe web injection with phytohemagglutinin-P. In addition, sera
      samples were collected after different antigen inoculations to investigate
      antibody responses. At day 28 of age, three randomly selected birds from each pen
      were euthanized to evaluate the relative weights of lymphoid organs. Results
      showed that dietary supplementation of both antibiotics increased (P<0.01) feed
      intake during 1 to 42 days of age. Furthermore, daily weight gain was influenced
      (P<0.01) by dietary treatments throughout the trial, so that the birds fed on
      antibiotics and 20 to 80 mg/kg genistein diets revealed the greater weight gains
      compared with other experimental groups. The best (P<0.05) feed conversion ratio
      assigned to the birds fed on diets containing antibiotics and moderate levels (40
      to 80 mg/kg) of genistein. Although the relative weights of thymus (P<0.05) and
      bursa of Fabricius (P<0.01) were greater in birds fed on genistein-supplemented
      diets compared with antibiotics-supplemented birds, the spleen weight was not
      affected by experimental diets. Similarly, CBH response and antibody titers
      against Newcastle and infectious bronchitis disease viruses were markedly
      (P<0.05) greater in chicks fed on diets supplemented with 20 to 80 mg/kg of
      genistein. Interestingly, the higher dosages of genistein suppressed CBH and
      antibody responses to the levels seen by control and antibiotics chicks. Dietary
      inclusion of genistein increased (P<0.05) lymphocytes and subsequently reduced
      (P<0.01) heterophil to lymphocyte ratio. The present findings indicate that
      dietary genistein supplementation at the levels of 20 to 80 mg/kg not only
      improves growth performance, but also could beneficially affect immunological
      responses in broiler chicks.

PMID- 25998983
TI  - Diagnostic accuracy of disorganization of the retinal inner layers in detecting
      macular capillary non-perfusion in diabetic retinopathy.
AB  - BACKGROUND: Disorganization of the retinal inner layers (DRIL) on optical
      coherence tomography (OCT) is thought to represent retinal capillary non
      perfusion (CNP) in eyes with diabetic retinopathy. This study was designed to
      evaluate the ability of DRIL to accurately predict CNP. DESIGN: Retrospective
      masked reliability and diagnostic accuracy study performed in the National
      Institute for Health Research (NIHR) Moorfields Biomedical Research Centre,
      London, UK SAMPLES: Retinal images of patients with diabetic retinopathy METHODS:
      The OCT images from 90 separate areas of angiographically confirmed perfused and
      non-perfused areas of the macula from 37 eyes of 31 patients were anonymized and
      coded. Two masked graders independently graded these OCT scans for the presence
      or absence of DRIL to determine the intergrader reliability. The diagnostic
      accuracy of DRIL in identifying CNP was evaluated from the results obtained. MAIN
      OUTCOME MEASURES: Sensitivity and specificity of DRIL in accurately detecting CNP
      RESULTS: The intergrader agreement was high with a Cohen's kappa of 0.909. DRIL
      was present in 84.4% (38/45) of non-perfused retina and none in perfused retina
      (0/45). The sensitivity and specificity of DRIL in detecting angiographic
      evidence of CNP was 84.4% and 100%, respectively. The positive predictive value
      was 100% and the negative predictive value was 86.5%. CONCLUSIONS: The presence
      of DRIL is a reliable predictor of areas of macular CNP. However, DRIL is not a
      universal finding of non-perfusion, with some cases exhibiting absence of DRIL
      despite angiographic CNP.

PMID- 25998984
TI  - Overexpression of neogenin inhibits cell proliferation and induces apoptosis in
      human MDA-MB-231 breast carcinoma cells.
AB  - Neogenin has been documented as playing an important role in cancer development.
      Although an elevated expression of neogenin has been detected in human breast
      cancer, the role of neogenin in breast cancer cells is not clearly understood. In
      the present study, we investigated neogenin in breast cancer cell proliferation,
      migration and apoptosis. We found that neogenin overexpression markedly reduced
      the proliferation and migration of breast cancer cells (P<0.05). Neogenin
      overexpression resulted in a reduction in the apoptosis rate. Inhibition of
      neogenin expression by neogenin siRNA dramatically promoted the proliferation and
      migration of breast cancer cells, whereas it inhibited cell apoptosis.
      Furthermore, we found that BMP-2-induced phosphorylation of Smad1/5/8 which was
      inhibited by neogenin overexpression. The present study demonstrates that
      neogenin may be a tumor suppressor in breast cancer. Neogenin may serve as a
      potential diagnostic marker and therapeutic target for breast cancer. 

PMID- 25998985
TI  - Recommendations for treatment of lymphomatoid papulosis with methotrexate: a
      report from the Dutch Cutaneous Lymphoma Group.

PMID- 25998987
TI  - Liver X receptor activation enhances CVB3 viral replication during myocarditis by
      stimulating lipogenesis.
AB  - AIMS: Viral myocarditis (VM) is severe cardiac inflammation that can result in
      sudden death or congestive heart failure in previously healthy adults, with no
      effective therapy. Liver X receptor (LXR) agonists have both anti-inflammatory
      and lipid-lowering properties. This study investigates whether LXR agonist
      T0901317 may modulate viral replication and cardiac inflammation during VM.
      METHODS AND RESULTS: (i) Adult mice were administered T0901317 or vehicle with
      the onset of inflammation during CVB3 virus myocarditis or (ii) treated 2 days
      prior to CVB3 infection. Against what we expected, T0901317 treatment did not
      alter leucocyte infiltration after CVB3 infection; yet pre-administration with
      T0901317 resulted in increased mortality upon CVB3 infection, higher cardiac
      viral presence, and increased cardiomyocyte damage when compared with the
      vehicle. Furthermore, we show a correlation of fatty acid synthase (FAS) and
      sterol regulatory element-binding protein 1c (SREBP-1c) with CVB3 viral load in
      the heart and that T0901317 is able to enhance the cardiac expression of FAS and
      SREBP-1c. Finally, we show in vitro that T0901317 is able to exaggerate CVB3
      mediated damage of Vero cells, whereas inhibitors of FAS and the SREBP-1c reduce
      the viral presence of CVB3 in neonatal cardiomyocytes. CONCLUSION: LXR agonism
      does not modulate cardiac inflammation, but exacerbates virus-mediated myocardial
      damage during VM by stimulating lipid biosynthesis and enhancing CVB3
      replication.

PMID- 25998988
TI  - Malignant Rhabdoid Tumor with Cervical Vertebra Involvement in a Teenage Child:
      Case Report and Review of the Literature.
AB  - Malignant rhabdoid tumor (MRT) is a highly malignant and aggressive tumor
      associated with the kidney that is mainly seen in children under 5 years old,
      resulting in a rapid fatal outcome. MRT invasion of the cervical vertebra is an
      extremely rare form of this malignancy. This study presents a case of MRT
      involving the C4 vertebra and its appendix. A 13-year-old girl was found to have
      vague neck pain and a mass in the left neck area of the mid-cervical spine.
      Percutaneous needle biopsy was performed and the histological and
      immunohistochemical analysis pointed towards a rhabdoid tumor. Chemotherapy and
      radiotherapy were performed, but the tumor mass progressively enlarged.
      Tumorectomy was conducted followed by another 6 courses of chemotherapy and
      (125)I radioactive seed implantation. Unfortunately, the C4 vertebra and its
      appendix were found to be abnormal 3 months after the end of therapy. The patient
      received an additional tumorectomy, internal fixation with C4 reconstruction by a
      combined anterior and posterior approach, and 6 courses of consolidation
      chemotherapy. She is still alive 40 months since the initial diagnosis and
      remains asymptomatic 31 months after the surgery.

PMID- 25998989
TI  - [Involuntary hospitalization under the Act of July 5th 2011: A study of patients'
      experience and understanding of their hearing with the judge ruling on civil
      detention cases].
AB  - OBJECTIVE: To assess involuntary admitted patients' experience and understanding
      of their hearing with the judge ruling on civil detention cases according to the
      Act of July 5th 2011. METHODS: The evaluation was conducted through face-to-face
      interviews, from a semi-structured questionnaire, with 48 involuntary admitted
      patients under psychiatric care admission on a third party request (ASPDT) or on
      state representative decision (ASPDRE) (participation rate=96%). RESULTS: Few
      participants knew the name of the hearing place (13%) and the judge's exact title
      (21%). About 58% of them had benefited from lawyer services. During the hearing,
      half of the patients contested the need for hospitalization. The judge was
      perceived as clear (79%), listening (69%) and benevolent (58%), but only 46% of
      patients believed that he/she was impartial and 35% that he/she was independent
      from medical decisions. More than half of the patients disagreed with the judge's
      decision (56%). However, only 19% of them planned to appeal. Three out of four
      were in favour of a judicial review of involuntary hospitalization. A feeling of
      protection was more common in people with a higher educational level (65% versus
      35%, Chi(2) (1) = 3.9, P = 0.05) and who suffered from mood disorders (75% versus
      46%, Chi(2) (1) = 3.8, P = 0.05). A feeling of being accused was more frequent in
      persons with hospitalization under psychiatric care admission on state
      representative decision (ASPDRE) than on a third party request (ASPDT) (37% vs
      10%, Chi(2) (1) = 4.9, P = 0.03). Persons under guardianship were also more
      likely to report such feelings (32% versus 10%, Chi(2) (1) = 3.4, P=0.06). The
      feeling that "everything was preordained" was more common in younger patients (m
      = 36.4 years [SD = 13.9] vs m = 46.2 years [SD = 17.8], t-test [46] = 2.01, P =
      0.04), as well as among those who used the advice of a lawyer, with an
      association at a trend level (73% versus 46%, Chi(2) (1) = 3.5, P = 0.06).
      CONCLUSION: Systematic judicial review of involuntary hospitalization represents
      a major evolution in the patients' rights field. This study shows that their
      experience and understanding of the hearing with the judge ruling on civil
      detention cases are quite mixed. In clinical practice, informing the patient
      about the upcoming hearing may allow the physician who initiates the
      hospitalization to reassure him/her as the intervention of a third party will be
      required to confirm the legality of involuntary admission. Furthermore, such
      information about the judicial intervention might avoid unproductive
      confrontation between the patient and the physician when the person remains
      opposed to the hospitalization. However, some patients may be disappointed as
      they are heavily invested in the preparation of their "defence" and have high
      hopes in the intervention of a judge who most often maintains the
      hospitalization.

PMID- 25998990
TI  - Analytical Quality by Design in pharmaceutical quality assurance: Development of
      a capillary electrophoresis method for the analysis of zolmitriptan and its
      impurities.
AB  - A fast and selective CE method for the determination of zolmitriptan (ZOL) and
      its five potential impurities has been developed applying the analytical Quality
      by Design principles. Voltage, temperature, buffer concentration, and pH were
      investigated as critical process parameters that can influence the critical
      quality attributes, represented by critical resolution values between peak pairs,
      analysis time, and peak efficiency of ZOL-dimer. A symmetric screening matrix was
      employed for investigating the knowledge space, and a Box-Behnken design was used
      to evaluate the main, interaction, and quadratic effects of the critical process
      parameters on the critical quality attributes. Contour plots were drawn
      highlighting important interactions between buffer concentration and pH, and the
      gained information was merged into the sweet spot plots. Design space (DS) was
      established by the combined use of response surface methodology and Monte Carlo
      simulations, introducing a probability concept and thus allowing the quality of
      the analytical performances to be assured in a defined domain. The working
      conditions (with the interval defining the DS) were as follows: BGE, 138 mM (115
      150 mM) phosphate buffer pH 2.74 (2.54-2.94); temperature, 25 degrees C (24-25
      degrees C); voltage, 30 kV. A control strategy was planned based on method
      robustness and system suitability criteria. The main advantages of applying the
      Quality by Design concept consisted of a great increase of knowledge of the
      analytical system, obtained throughout multivariate techniques, and of the
      achievement of analytical assurance of quality, derived by probability-based
      definition of DS. The developed method was finally validated and applied to the
      analysis of ZOL tablets.

PMID- 25998986
TI  - Intracellular signalling during neutrophil recruitment.
AB  - Recruitment of leucocytes such as neutrophils to the extravascular space is a
      critical step of the inflammation process and plays a major role in the
      development of various diseases including several cardiovascular diseases.
      Neutrophils themselves play a very active role in that process by sensing their
      environment and responding to the extracellular cues by adhesion and de-adhesion,
      cellular shape changes, chemotactic migration, and other effector functions of
      cell activation. Those responses are co-ordinated by a number of cell surface
      receptors and their complex intracellular signal transduction pathways. Here, we
      review neutrophil signal transduction processes critical for recruitment to the
      site of inflammation. The two key requirements for neutrophil recruitment are the
      establishment of appropriate chemoattractant gradients and the intrinsic ability
      of the cells to migrate along those gradients. We will first discuss signalling
      steps required for sensing extracellular chemoattractants such as chemokines and
      lipid mediators and the processes (e.g. PI3-kinase pathways) leading to the
      translation of extracellular chemoattractant gradients to polarized cellular
      responses. We will then discuss signal transduction by leucocyte adhesion
      receptors (e.g. tyrosine kinase pathways) which are critical for adhesion to, and
      migration through the vessel wall. Finally, additional neutrophil signalling
      pathways with an indirect effect on the neutrophil recruitment process, e.g.
      through modulation of the inflammatory environment, will be discussed.
      Mechanistic understanding of these pathways provide better understanding of the
      inflammation process and may point to novel therapeutic strategies for
      controlling excessive inflammation during infection or tissue damage. 

PMID- 25998991
TI  - Managing critically Ill hematology patients: Time to think differently.
AB  - The number of patients living with hematological malignancies (HMs) has increased
      steadily over time. This is the result of intensive and effective treatments that
      also increase the probability of infiltrative, infectious or toxic life
      threatening event. Over the last two decades, the number of patients with HMs
      admitted to the ICU increased and their mortality has dropped sharply. ICU
      patients with HMs require an extensive diagnostic workup and the optimal use of
      ICU treatments to identify the reason for ICU admission and the nature of the
      complication that explains organ dysfunctions. Mortality of ARDS or septic shock
      is up to 50%, respectively. In this review, the authors share their experience
      with managing critically ill patients with HMs. They discuss the main aspects of
      the diagnostic and therapeutic management of critically ill patients with HMs and
      argue that outcomes have improved over time and that many classic determinants of
      mortality have become irrelevant.

PMID- 25998992
TI  - Haemophilus parainfluenzae aortic prosthetic valve endocarditis (PVE)
      successfully treated with oral levofloxacin.
AB  - Antibiotic treatment of native valve infective endocarditis (IE) traditionally
      consists of 4-6 weeks of intravenous (IV) antibiotic therapy. Oral (PO)
      antibiotic therapy is being used more frequently, for part or all of treatment
      for IE but experience in treating IE with PO antibiotics is limited. Preferable
      agents for oral therapy of IE are antibiotics with a high degree of activity
      against the IE pathogen and that have high bioavailability (>90%) so that
      achievable serum and tissue levels are the same as with equivalent IV
      antibiotics. Oral antibiotic therapy of IE has several advantages over IV therapy
      given the long duration of treatment, i.e., 4-6 weeks for IE. Firstly, outpatient
      oral therapy for IE is easily administered over 4-6 weeks and decreases hospital
      length of stay (LOS). Secondly, oral antibiotics (administered at the same dose,
      frequency and duration) costs much less than their IV counterparts. Thirdly, with
      PO therapy for IE there are no central venous catheter (CVC) associated
      complications, e.g., phlebitis, bacteremia, fungemia. Compared to native valve
      IE, prosthetic valve endocarditis (PVE), depending on the IE pathogen, requires
      prolonged therapy and usually valve replacement. Haemophilus sp. IE is relatively
      virulent and often complicated by heart failure and/or embolic phenomena. We
      describe the first reported case of Haemophilus parainfluenzae aortic PVE
      successfully treated with oral levofloxacin without aortic valve replacement. 

PMID- 25998994
TI  - Human Papillomavirus 16 Variants May Be Identified by E6 Gene Analysis.
AB  - AIMS: The aims of the study were (1) to characterize the genetic variability of
      human papillomavirus (HPV) genotype 16 in the E6 region when this genotype is
      present in multiple infection samples, (2) to assess the prevalence of variants
      in our region and (3) to analyze the relationship between variants, patients'
      ages and pathology. METHODS: The Clinical Microbiology and Infection Control
      Department analyzed samples which were positive for genotype 16 and other
      genotypes from 2007 to 2013. Variants were assigned to European, Euro-German,
      Asian, Asian-American or African lineage by sequence analysis. The relationship
      among variants, age and different types of lesion was studied. RESULTS: In HPV-16
      sequence analysis, the European variant was detected in 85.10% of samples, the
      Asian-American in 7.80%, the African in 4.25% and the Euro-German in 2.83% of
      specimens. Sequence genetic variability showed 16 nucleotide substitutions.
      Moreover, non-European variants were mainly found in old women and in isolates
      from high-grade squamous intraepithelial lesions since European variants were
      mainly detected in negative cytologies. CONCLUSION: Multiple infections may take
      effect on nucleotide substitution and the appearance of recombinant samples.
      Single gene analysis makes it impossible to detect recombination which has a
      great influence on drug response and vaccine strategies. Thus, E6 gene analysis
      would be enough to identify HPV-16 intratypic variants but not to confirm the
      results.

PMID- 25998993
TI  - The relation between platelet-to-lymphocyte ratio and Pulmonary Embolism Severity
      Index in acute pulmonary embolism.
AB  - PURPOSE: In this study, we aimed to investigate the value of the platelet-to
      lymphocyte ratio (PLR) for predicting disease severity based on simplified
      Pulmonary Embolism Severity Index (sPESI), as well as in-hospital mortality in
      patients with acute pulmonary embolism (APE). MATERIALS AND METHODS: Our
      hospital's electronic patient database was searched for the patients with ICD-9
      code I26, and eligible 646 patients were included in the study. RESULTS:
      Univariate logistic regression analysis showed that PLR, pulmonary artery
      systolic pressure, right ventricular dysfunction, D-dimer level, and white blood
      cell, lymphocyte, platelet and neutrophil counts were significantly correlated
      with a high sPESI score in patients with APE. CONCLUSIONS: To the best of our
      knowledge, this is the first study in the literature showing that a high PLR is
      independently associated with a high risk of mortality in patients with APE.

PMID- 25998995
TI  - Folic acid conjugated ferritins as photosensitizer carriers for photodynamic
      therapy.
AB  - We coupled folic acid as a tumour targeting ligand to the surface of ferritins
      and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone
      in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed
      tumour growth and tumour metastasis. 

PMID- 25998996
TI  - Transarterial chemoembolization for hepatocellular carcinoma: An old method, now
      flavor of the day.
AB  - Transarterial chemoembolization (TACE) is the recommended treatment for patients
      suffering from intermediate, B stage, hepatocellular carcinoma. Despite an
      undisputed pharmacokinetic advantage, TACE with microspheres has not been shown
      to be superior in terms of survival compared to conventional TACE using
      Lipiodol((r)). The best guarantee to reduce toxicity and maximize the efficacy of
      TACE is to strictly observe the contraindications for the procedure (Child
      Pugh>B8, reduced portal flow, very large tumor, any technical contraindication
      and renal impairment), and rigorous application of the administration
      requirements for the Lipiodol((r)) emulsion or loaded microspheres (assessment of
      hepatic vascularization investigating for accessory vascularization, injection
      methods). Tumor response should be assessed after four weeks by CT or MRI using
      the modified RECIST criteria. 

PMID- 25998997
TI  - Radiological treatment of HCC: Interventional radiology at the heart of
      management.
AB  - Interventional radiology is involved practically at each stage in the treatment
      of hepatocellular carcinoma, as recommended in the EASL-EORTC guidelines. It is
      even becoming more important as technological advances progress and as its long
      term efficacy is assessed. Used curatively, thermoablation can obtain five-year
      survival rates of 40 to 70%, with a survival rate of 30% at 10years. As there are
      many tools available in order to be used, it requires a thorough pre-treatment
      assessment and discussion in a multidisciplinary team meeting. Regular patient
      reassessment is needed in order to be able to adjust treatment because of the
      complementarity of the treatments available and the course of the disease. 

PMID- 25998999
TI  - Is there a gold standard for management of the difficult airway?
AB  - Numerous practice guidelines have been developed to assist clinicians in the
      management of the difficult airway. The nature of difficult airway management,
      however, does not provide a practical way of comparing different guidelines or
      algorithms; no evidence supports one set of guidelines over another. Nevertheless
      they play an important role in patient safety as dissemination of such guidelines
      encourages airway practitioners to consider their strategies and formulate
      specific plans for the management of a predicted or unexpected difficult airway. 

PMID- 25998998
TI  - CYP2D6 genetic polymorphisms and their relevance for poisoning due to
      amfetamines, opioid analgesics and antidepressants.
AB  - INTRODUCTION: Cytochrome P450 2D6 (CYP2D6) is a member of the cytochrome P450
      (CYP) superfamily involved in the biotransformation of drugs and substances of
      abuse encountered in clinical toxicology. Among the CYP superfamily, the CYP2D6
      gene is considered as the most polymorphic as more than 105 different alleles
      have been identified so far. CYP2D6 genetic polymorphisms have the potential to
      affect the toxicity of their substrates. OBJECTIVE: This review will focus
      specifically on CYP2D6 genetic polymorphisms and their relevance for poisoning
      due to amfetamines, opioid analgesics and antidepressants in humans. METHODS:
      PubMed (up to August 2013) was searched with the following selection criteria:
      'CYP2D6 AND (toxicology OR poisoning OR intoxication OR overdose)'. Of the 454
      citations retrieved, only 46 papers dealt with the impact of CYP2D6 polymorphisms
      on poisoning due to amfetamines, opioid analgesics and antidepressants.
      amfetamines. While some in vitro studies suggest that CYP2D6-mediated metabolites
      of 3,4-methylenedioxymethamfetamine (MDMA) are substantially more cytotoxic
      compared with unchanged MDMA, it is not yet confirmed in human cases of MDMA
      intoxication that extensive/ultra-rapid CYP2D6 metabolisers could be at higher
      risk. This would also apply to methamfetamine exposure and the related cardiac
      and central nervous system toxicity. Opioid analgesics. CYP2D6 ultra-rapid
      metabolisers are more likely to experience the adverse effects of codeine and
      tramadol. Opioid analgesics that do not rely on CYP2D6 for therapeutic activity,
      such as morphine and hydromorphone, may therefore be a better alternative to
      codeine and tramadol, with the limitation that these drugs have their own set of
      adverse reactions. Antidepressants. CYP2D6 poor metabolisers are generally more
      prone to adverse effects. Among them, the four drugs with the highest level of
      evidence are amitriptyline, nortriptyline, venlafaxine and fluoxetine. Further
      data are needed, however, for doxepin and paroxetine, while citalopram adverse
      effects seem definitely less influenced by CYP2D6 genetic polymorphisms.
      CONCLUSIONS: Either poor or extensive/ultra-rapid CYP2D6 metabolisers may be
      exposed to toxic effects of amfetamines, opioid analgesics and antidepressants.
      In these three categories, the level of evidence is substance dependent, with
      differences within the same pharmacological class.

PMID- 25999000
TI  - Strengths and limitations of airway techniques.
AB  - After a prolonged period of stagnation, many new airway devices have entered the
      clinical arena. Along with these, practice guidelines based primarily on expert
      opinion have been endorsed by specialty societies. These guidelines encourage a
      rational progression in strategies rather than persistent ineffective efforts. It
      is important to have an understanding of the strengths and limitations of the
      devices and strategies relating to ventilation by face mask and supraglottic
      airway, the variety of fiberoptic and video laryngoscopic techniques, and the
      methods of reestablishing the airway after failed extubation. 

PMID- 25999001
TI  - Assessment before airway management.
AB  - It is wise to plan and prepare for the unexpected difficult airway. Although it
      is essential to take a history and examine every patient prior to airway
      management, preoperative anticipation of a difficult airway occurs in only 50% of
      patients subsequently found to have a difficult airway. Bedside screening tests
      lack accuracy. The modified Mallampati test and the measurement of thyromental
      distance are unreliable for prediction of difficult tracheal intubation.
      Knowledge of risk factors for various airway management techniques may help when
      devising an airway management plan. 

PMID- 25999002
TI  - Predictors of difficult intubation and the otolaryngology perioperative consult.
AB  - Airway management is one of the most important aspects of anesthesia care.
      Although the incidence of difficult intubation is low, predicting a potentially
      difficult airway can ensure that necessary staff and equipment are available. A
      preoperative airway evaluation should include a history and physical examination
      focusing on elements that can cause problems with intubation. When indicated,
      flexible fiberoptic laryngoscopy can add valuable information regarding the upper
      aerodigestive anatomy. Specific patient and situational factors should be
      considered. Alternative plans should be defined before the initiation of
      anesthesia. Management of a complex airway should be a coordinated effort between
      anesthesiologists and otolaryngologists. 

PMID- 25999003
TI  - Airway anesthesia: theory and practice.
AB  - Topical anesthesia of the airway is a necessary for awake intubation and is
      usually achieved using lidocaine delivered by various means. Although some
      experts favor the use of airway blocks, a more common approach is to use pure
      topical methods in combination with "spray as you go" techniques. Once the
      topicalization is complete, the patient should be able to easily tolerate the use
      of an oral airway used to facilitate awake oral intubation. Nasal intubation
      requires additional topicalization of the nasal passages in conjunction with a
      vasoconstrictor. Finally, judicious sedation is frequently used when awake
      intubation is carried out. 

PMID- 25999004
TI  - Obstructive sleep apnea, sleep disorders, and perioperative considerations.
AB  - Data suggest that surgical patients with obstructive sleep apnea (OSA) may be
      difficult to ventilate and intubate, and may be prone to postoperative
      complications. This article addresses the identification of patients at risk for
      OSA, epidemiology of the disorder, and treatment options, as well as the
      perioperative management of this population. 

PMID- 25999005
TI  - Clinical evaluation and airway management for adults with cervical spine
      instability.
AB  - Airway management of patients with cervical spine instability may be difficult as
      a result of immobilization, and may be associated with secondary neurologic
      injury related to cervical spine motion. Spinal cord instability is most common
      in patients with trauma, but there are additional congenital and acquired
      conditions that predispose to subacute cervical spine instability. Patients with
      suspected instability should receive immobilization during airway management with
      manual in-line stabilization. The best strategy for airway management is one that
      applies the technique with the highest likelihood of success on the first attempt
      and the lowest biomechanical influence on a potentially unstable spine. 

PMID- 25999006
TI  - Infections and edema.
AB  - Infectious and inflammatory conditions of the head and neck may present with
      impaired airways. An understanding of the pathophysiology will allow for accurate
      diagnosis and prompt intervention. Preintervention discussion and planning by
      members of the airway team are crucial in developing a primary and backup plans
      for safely securing the airway. 

PMID- 25999007
TI  - Anesthesia care for the professional singer.
AB  - The professional singer comes to the day of surgery with a measure of anxiety
      about the effects of anesthesia or surgery on his or her voice. A detailed
      informed consent should be obtained to discuss and document risks, as well as set
      realistic expectations for recovery. The smallest endotracheal tube possible
      should be used to intubate in the least traumatic way. Movement of the tube
      should be minimized, both during anesthesia, as well as in emergence.
      Postoperative care may be coordinated with an otolaryngologist and speech
      language pathologist as the singer plans a return to performance. 

PMID- 25999008
TI  - The role of cricothyrotomy, tracheostomy, and percutaneous tracheostomy in airway
      management.
AB  - Cricothyrotomy, percutaneous dilation tracheostomy, and surgical tracheostomy are
      cost-effective and safe techniques employed in the management of critically ill
      patients requiring insertion of an artificial airway. These procedures have been
      well characterized and studied in the surgical, emergency medicine, and critical
      care literature. This article focuses on the role of each of these modalities in
      airway management, specifically comparing the data for each procedure in regard
      to procedural outcomes. The authors discuss the techniques available and the
      relevant background data regarding choice of each method and its integration into
      clinical practice. 

PMID- 25999009
TI  - Integration of a difficult airway response team into a hospital emergency
      response system.
AB  - Hospital-wide emergency response teams have been an area of development for
      several decades. Highly specialized to address emergent needs, they mimic the
      cardiac-pulmonary arrest teams established at hospitals nationwide, such as heart
      attack, brain attack, medical emergency, rapid response, and difficult airway
      response teams (DART). The DART at Johns Hopkins Hospital is a collaboration of
      the Anesthesiology and Critical Care Medicine, Otolaryngology-Head and Neck
      Surgery, General Surgery, and Emergency Medicine departments. This successful
      model may be used by other hospitals to establish improved and comprehensive care
      of the difficult airway patient. 

PMID- 25999010
TI  - Preparedness and education in airway management.
AB  - A prepared airway practitioner performs safe airway management, displaying skill,
      knowledge, and a full awareness of human factors, within a culture of safety. The
      education of prepared practitioners should include deliberate practice and
      distributed learning and should aim for expertise rather than mere competence.
      Translational outcomes from improved education and training can significantly
      decrease patient morbidity and mortality. 

PMID- 25999011
TI  - What We All Should Know About Our Patient's Airway: Difficult Airway
      Communications, Database Registries, and Reporting Systems Registries.
AB  - Documentation and dissemination of patient information characterizing a difficult
      airway encounter is a critical safety link between past, present, and future
      health care providers. Effective communication of the nature of the difficulty
      encountered and the airway management techniques used consists of documentation
      in the patient's medical record for concurrent care providers and dissemination
      of that information to the patient and future providers for use during subsequent
      episodes of care. Significant progress has been made with developing national and
      international electronic patient record systems and airway databases, but full
      integration has yet to be achieved. 

PMID- 25999012
TI  - Airway management.

PMID- 25999013
TI  - Airway management.

PMID- 25999014
TI  - Desensitization to rituximab in a multidisciplinary setting.
AB  - BACKGROUND: The need to offer first-line therapy to the increasing number of
      patients who have suffered an hypersensitivity reaction has stimulated the use of
      rapid desensitization protocols. OBJECTIVE: To present our experience working as
      a multidisciplinary team using a rituximab rapid desensitization scheme. METHOD:
      Patient demographics, allergic reaction, skin tests to rituximab, number of
      desensitizations, reactions during the desensitization protocol and actions
      taken, number of administered and completed cycles, were retrospectively
      collected in patients who received at least one desensitization to rituximab.
      MAIN OUTCOMES: Number of desensitizations successfully managed. RESULTS: Between
      2012 and June 2013 five patients received a total of 19 desensitizations to
      rituximab using a 12 step rapid desensitization protocol. All patients received
      the scheduled chemotherapeutic cycles as inpatients, with no delay in
      administration dates. Three patients presented a hypersensitivity reaction during
      the first desensitization and in one patient the event occurred again during the
      second treatment cycle. All reactions occurred in the last step, when the
      infusion rate reached the maximum speed. CONCLUSION: The developed protocol for
      rapid desensitization was successful in five patients receiving rituximab.
      Patients could receive the full intended dose.

PMID- 25999015
TI  - Structural elucidation and biological studies of a novel exopolysaccaride from
      Klebsiella pneumoniae PB12.
AB  - An exopolysaccharide (KNPS) of an average molecular weight ~1.8*10(5) Da was
      isolated from the culture medium of Klebsiella pneumoniae PB12. Structural
      characterization of KNPS was carried out using sugar and methylation analysis,
      Smith degradation and 1D/2D NMR experiments. Sugar analysis showed that the KNPS
      composed of arabinose, galactose, 3-O-methyl-galctose and glucose in a molar
      ratio of nearly 4:3:1:1. The proposed repeating unit of the KNPS has a backbone
      chain consisting of two (1->6)-galactopyranosyl residues, two (1->5)
      arabinofuranosyl residues, one (1->6)-glucopyranosyl residue and one (1->3)
      arabinopyranosyl residue, out of which one (1->6)-galactopyranosyl residue was
      branched at O-2 position with a (1->2)-linked-galactopyranosyl residue terminated
      with non reducing arabinofuranosyl residue and one (1->5)-arabinofuranosyl
      residue branched at O-3 position with non reducing end 3-O-Me-galactopyranosyl
      residue. KNPS was found non-toxic toward human lymphocyte up to the dosage of 100
      MUg/ml. KNPS enhanced malondialdehyde (MDA), reactive oxygen species (ROS), and
      have the potential to alter the ratio of oxidized glutathione (GSSG) and reduced
      glutathione (GSH) levels in the cellular system.

PMID- 25999016
TI  - Chemical and pharmacological profiles of Echinacea complex.
AB  - Echinacea purpurea has a long history in traditional medicine. To verify the
      pharmacological efficacy of active principles, a polysaccharide-phenolic-protein
      complex has been isolated from flowering parts of herb by alkaline extraction. It
      showed on GPC and HPLC one peak of molecular mass around 10 kDa. Chemical and
      spectroscopic analyses revealed carbohydrate, phenolic and protein contents in
      Echinacea complex. Pharmacological tests have shown its marked cough suppressing
      and bronchodilatory effects. The antitussive effect of Echinacea was similar to
      the narcotic drug codeine and the bronchodilatory effect was more significant
      than salbutamol, the antiasthmatic drug used in a clinical practice.
      Pharmacodynamic study shows the beneficial effects of Echinacea complex on the
      respiratory system and highlights the great potential for development of
      antitussive and bronchodilatory drugs from natural sources.

PMID- 25999017
TI  - MicroRNA-130a Targets MAP3K12 to Modulate Diabetic Endothelial Progenitor Cell
      Function.
AB  - AIMS: The aim of the present study was to explore the influence of microRNA (miR)
      130a dysregulation on the JNK signal pathway through its target MAP3K12 in
      diabetic endothelial progenitor cells (EPCs). METHODS: The expression of miR-130a
      was compared between diabetic and normal EPCs. Computational target prediction
      was performed to identify MAP3K12 as a functionally relevant target of miR-130a
      in EPCs. The role of miR-130a was investigated regarding its anti-apoptotic
      effects and its role on the regulation of EPC function was evaluated through the
      negative regulation of the JNK signal pathway RESULTS: MiR-130a expression was
      significantly downregulated in diabetic EPCs, and cell proliferation was reduced
      in EPCs under high glucose condition. miR-130a inhibited the JNK pathway by
      targeting MAP3K12, contributing to its anti-apoptotic effect and the maintenance
      of EPC function. In diabetic EPCs, high glucose affects the expression of miR
      130a, inducing sustained JNK activation and promoting EPC apoptosis and
      dysfunction. CONCLUSIONS: Downregulation of miR-130a may underlie endothelial
      dysfunction in diabetes through the activation of JNK signal pathway.

PMID- 25999018
TI  - ESR Position Paper on Imaging Biobanks.
AB  - In March 2014 the European Society of Radiology (ESR) established a dedicated
      working group (ESR WG on Imaging Biobanks) aimed at monitoring the existing
      imaging biobanks in Europe, promoting the federation of imaging biobanks and
      communication of their findings in a white paper. The WG provided the following
      statements: (1) Imaging biobanks can be defined as "organised databases of
      medical images and associated imaging biomarkers (radiology and beyond) shared
      among multiple researchers, and linked to other biorepositories". (2) The
      immediate purpose of imaging biobanks should be to allow the generation of
      imaging biomarkers for use in research studies and to support biological
      validation of existing and novel imaging biomarkers. (3) A long-term scope of
      imaging biobanks should be the creation of a network/federation of such
      repositories integrated with the already-existing biobanking network. The aim of
      the WG was to investigate the existence, consistency, geographical distribution
      and type of imaging biobanks in Europe. A survey among ESR members resulted in
      the identification of 27 imaging biobanks, mostly disease-oriented and designed
      for research and clinical reference. In 80 % access to imaging biobanks is
      restricted. Key points * Imaging biobanks are "shared databases of imaging
      biomarkers, linked to biorepositories".* Exploitation of traditional and imaging
      biobanks is meaningful for "personalised medicine".* A European imaging biobank
      network would significantly boost research in the imaging domain. 

PMID- 25999019
TI  - RNA structures are involved in the thermoregulation of bacterial virulence
      associated traits.
AB  - Pathogenic bacteria are exposed to temperature changes during colonization of the
      human body and during exposure to environmental conditions. Virulence-associated
      traits are mainly expressed by pathogenic bacteria at 37 degrees C. We review
      different cases of post-transcriptional regulation of virulence-associated
      proteins through RNA structures (called RNA thermometers or RNATs) that modulate
      the translation of mRNAs. The analysis of RNATs in pathogenic bacteria has
      started to produce a comprehensive picture of the structures involved, and of the
      genes regulated by this mechanism. However, we are still not able to predict the
      functionality of putative RNATs predicted by bioinformatics methods, and there is
      not a global approach to measure the effect of these RNA structures in gene
      regulation during bacterial infections. 

PMID- 25999020
TI  - The Essential Oil from Origanum vulgare L. and Its Individual Constituents
      Carvacrol and Thymol Enhance the Effect of Tetracycline against Staphylococcus
      aureus.
AB  - BACKGROUND: In an ongoing project to evaluate essential oils as modulators of
      antibiotic resistance, the essential oil from Origanum vulgare L. (OVEO), as well
      as its individual constituents carvacrol (CAR) and thymol (THY), were
      investigated using Staphylococcus aureus strains possessing efflux mechanisms of
      resistance to norfloxacin, erythromycin and tetracycline. METHODS: The minimum
      inhibitory concentration (MIC) values of the antibiotics were determined by agar
      dilution method, in the absence and in the presence of subinhibitory
      concentrations of OVEO, CAR or THY. RESULTS: Along with relevant
      antistaphylococcal activity, OVEO, CAR and THY modulated the activity of
      tetracycline, i.e. in combination with antibiotics a reduction in the MIC was
      observed (up to fourfold). CONCLUSIONS: The results presented here represent, as
      far as we know, the first report of OVEO, CAR and THY as putative efflux pump
      inhibitors. Broadly, these findings indicate that essential oils could serve as
      potential sources of compounds capable of modulating drug resistance.

PMID- 25999021
TI  - Recommendations on pre-hospital & early hospital management of acute heart
      failure: a consensus paper from the Heart Failure Association of the European
      Society of Cardiology, the European Society of Emergency Medicine and the Society
      of Academic Emergency Medicine.
AB  - Acute heart failure is a fatal syndrome. Emergency physicians, cardiologists,
      intensivists, nurses and other health care providers have to cooperate to provide
      optimal benefit. However, many treatment decisions are opinion-based and few are
      evidenced-based. This consensus paper provides guidance to practicing physicians
      and nurses to manage acute heart failure in the pre-hospital and hospital
      setting. Criteria of hospitalization and of discharge are described. Gaps in
      knowledge and perspectives in the management of acute heart failure are also
      detailed. This consensus paper on acute heart failure might help enable
      contiguous practice. 

PMID- 25999022
TI  - Hysteroscopic Intrauterine Adhesiolysis Using the "Ploughing" Technique With Cold
      Scissors.
AB  - STUDY OBJECTIVE: The majority of the current published literature describes
      hysteroscopic adhesiolysis (HA) for patients with intrauterine adhesions (IUA)
      using electrical instruments which may cause thermal injury to the endometrium.
      This video shows the procedure for HA using the "ploughing" technique with cold
      scissors. DESIGN: Step-by-step explanation of the technique using videos and
      pictures (educative video) (Canadian Task Force Classification III). SETTING:
      Third Xiangya Hospital of Central South University, Changsha, China. PATIENT: A
      39-year-old woman diagnosed with IUA. INTERVENTION: HA using the ploughing
      technique with cold scissors, followed by adjunct postoperative treatment with a
      follow up hysteroscopy 2 months later. MEASUREMENT AND MAIN RESULTS: The uterine
      cavity was successfully reopened, and the scars covering the inner uterine walls
      were ploughed longitudinally to release the contraction imposed by the scars, as
      well as to provide a fresh and rich blood-supplied surface for endometrium to
      grow and cover after the surgery. There were no complications. The follow-up
      hysteroscopy 2 months later revealed a normal uterine cavity and much improved
      endometrium, along with restoration of almost normal menses. CONCLUSION: HA using
      the ploughing technique with cold scissors is effective for rebuilding the
      uterine cavity even for patients with severe IUA. Its advantages merit further
      study.

PMID- 25999023
TI  - Emerging zoonoses: tackling the challenges.

PMID- 25999024
TI  - MicroRNA-218 inhibits the proliferation and metastasis of esophageal squamous
      cell carcinoma cells by targeting BMI1.
AB  - MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis
      either as oncogenes or as tumor suppressor genes. In the present study, we found
      that the expression level of miR-218 was significantly reduced in esophageal
      squamous cell carcinoma (ESCC) tissues and ESCC cell lines. Moreover, its
      expression was found to correlate with the clinicopathological stage of ESCC; miR
      218 expression was lower in the stage III tissue samples than in the stage I and
      II tissue samples. Furthermore, the decreased expression of miR-218 was found to
      be associated with an enhanced ESCC cell proliferation and metastasis. Western
      blot analysis and luciferase reporter assay revealed that miR-218 decreased BMI1
      expression by binding to the putative binding sites in its 3'-untranslated region
      (3'-UTR). The BMI1 mRNA expression levels were markedly increased and negatively
      correlated with the miR-218 expression level in the ESCC tissues. Functional
      analyses revealed that the restoration of miR-218 expression inhibited ESCC cell
      proliferation, migration and invasion and promoted apoptosis. The knockdown of
      BMI1 by siRNA showed the same phenocopy as the effect of miR-218 on ESCC cells,
      indicating that BMI1 was a major target of miR-218. In the present study, our
      findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel
      target of miR-218 in ESCC. Therefore, miR-218 may prove to be a useful biomarker
      for monitoring the initiation and development of ESCC, and may thus be an
      effective therapeutic target in ESCC.

PMID- 25999025
TI  - Intake of indigestible carbohydrates influences IgA response and polymeric Ig
      receptor expression in the rat submandibular gland.
AB  - Secretory IgA in the saliva is essential for protection from mucosally
      transmitted pathogens and maintaining homeostasis at mucosal surfaces of the oral
      cavity. Expression of submandibular gland polymeric Ig receptor (pIgR) is
      essential for IgA secretion. In the present study, we investigated the influence
      of indigestible carbohydrates on IgA production in the salivary gland and saliva.
      Five-week-old rats were fed a fibre-free diet (control), or a diet with 5 % (w/w)
      fructo-oligosaccharide (FOS) or a combination of 2.5 % (w/w) polydextrose (PDX)
      and 2.5 % (w/w) lactitol for 21-d. IgA concentrations in the caecal digesta,
      submandibular gland tissue, and saliva in the FOS and PDX+lactitol diet groups
      were significantly higher than those in the control group (P< 0.05). The increase
      in IgA in the submandibular gland tissue was confirmed using immunohistochemical
      analysis. However, the IgA concentrations of serum did not differ between the FOS
      or PDX+lactitol groups and the control group (P= 0.5). In the FOS and
      PDX+lactitol groups, the pIgR mRNA (pIgR/beta-actin) expression level in the
      submandibular gland tissue was significantly higher than that in the control
      group (P< 0.05). The present study suggests that indigestible carbohydrates play
      an important role in the increase in IgA concentrations in the submandibular
      gland tissue, saliva, and caecal digesta. 

PMID- 25999026
TI  - Evidence-based vector control? Improving the quality of vector control trials.
AB  - Vector-borne diseases (VBDs) such as malaria, dengue, and leishmaniasis cause a
      high level of morbidity and mortality. Although vector control tools can play a
      major role in controlling and eliminating these diseases, in many cases the
      evidence base for assessing the efficacy of vector control interventions is
      limited or not available. Studies assessing the efficacy of vector control
      interventions are often poorly conducted, which limits the return on investment
      of research funding. Here we outline the principal design features of Phase III
      vector control field studies, highlight major failings and strengths of published
      studies, and provide guidance on improving the design and conduct of vector
      control studies. We hope that this critical assessment will increase the impetus
      for more carefully considered and rigorous design of vector control studies. 

PMID- 25999027
TI  - Quantitative sequencing confirms VSG diversity as central to immune evasion by
      Trypanosoma brucei.
AB  - Antigenic variation is central to the virulence of African trypanosomes, where
      the VSG coat is used to evade the host immune system. Recent advances in
      technology have now allowed more secrets of this system to emerge, with the
      surprising insight that a broad repertoire of VSGs is rapidly expressed. This has
      major implications for how the parasite must evade the host immune response. 

PMID- 25999028
TI  - The impact of vitamin D deficiency on patients undergoing kidney transplantation:
      focus on cardiovascular, metabolic, and endocrine outcomes.
AB  - Vitamin D deficiency is common among kidney transplant (KT) recipients because of
      reduced sunlight exposure, low intake of vitamin D, the immunosuppressive drug
      regimen administered, and steroid therapy. Glucocorticoids regulate expression of
      genes coding for enzymes that catabolize vitamin D, further reducing its level in
      serum. Although vitamin D primarily regulates calcium homeostasis, vitamin D
      deficiency is associated with the risk of several diseases, such as diabetes
      mellitus and tuberculosis. Aim of this review is to highlight endocrine and
      metabolic alterations due to the vitamin D deficiency by evaluating the
      mechanisms involved in the development of KT-related disease (cardiovascular,
      bone mineral density, and new-onset diabetes after transplantation). Next, we
      review evidence to support a link between low vitamin D status and KT-related
      diseases. Finally, we briefly highlight strategies for restoring vitamin D status
      in KT patients. 

PMID- 25999029
TI  - Elevated Serum Angiopoietin-like Protein 2 in Patients with Acute Coronary
      Syndrome.
AB  - BACKGROUND AND AIMS: Angiopoietin-like protein 2 (Angptl2) is regarded as a
      proinflammatory factor in the pathogenesis of atherosclerosis and is expressed at
      high levels in patients with coronary artery disease. However, direct evidence of
      Angptl2 in acute coronary syndrome (ACS) is lacking. Our study was designed to
      investigate a possible relationship between serum Angptl2 and ACS. METHODS: We
      evaluated 251 consecutive patients undergoing coronary angiography, consisting of
      132 patients with ACS (unstable angina pectoris n = 60, acute myocardial
      infarction n = 72), 50 patients with stable angina pectoris, and 69 control
      patients. Serum Angptl2 concentration was measured in peripheral venous blood by
      an enzyme-linked immunosorbent assay. RESULTS: Serum Angptl2 levels were
      significant higher in patients with ACS than in those with stable angina (p
      <0.05) or controls (p <0.001). The difference between angplt2 levels in unstable
      angina and acute myocardial infarction subgroups was statistically insignificant
      (p = 0.831). In multivariable logistic regression models, using quartiles of
      Angptl2, Angptl2 was closely associated with ACS following adjustment of age,
      gender, established risk factors and high sensitivity C-reactive protein levels
      (odds ratio for quartile 4 vs. quartile 1: 10.182, 95% confidence interval 2.440
      42.485, p = 0.001). CONCLUSIONS: Serum Angptl2 is a new candidate biomarker for
      risk stratification of ACS.

PMID- 25999030
TI  - A luminescence switch-on probe for terminal deoxynucleotidyl transferase (TdT)
      activity detection by using an iridium(III)-based i-motif probe.
AB  - An iridium(III) complex exhibiting higher responce towards i-motif DNA over dsDNA
      and ssDNA was employed for the construction of a TdT activity detection platform.
      The assay exhibited a linear signal enhancement for TdT in the concentration
      range of 0 to 8 U mL(-1), and the limit of detection for TdT was 0.25 U mL(-1).

PMID- 25999031
TI  - Hospital Authority audit of the outcome of endoscopic resection of superficial
      upper gastro-intestinal lesions in Hong Kong.
AB  - OBJECTIVES: To review the short-term outcome of endoscopic resection of
      superficial upper gastro-intestinal lesions in Hong Kong. DESIGN: Historical
      cohort study. SETTING: All Hospital Authority hospitals in Hong Kong. PATIENTS:
      This was a multicentre retrospective study of all patients who underwent
      endoscopic resection of superficial upper gastro-intestinal lesions between
      January 2010 and June 2013 in all government-funded hospitals in Hong Kong. MAIN
      OUTCOME MEASURES: Indication of the procedures, peri-procedural and procedural
      parameters, oncological outcomes, morbidity, and mortality. RESULTS: During the
      study period, 187 lesions in 168 patients were resected. Endoscopic mucosal
      resection was performed in 34 (18.2%) lesions and endoscopic submucosal
      dissection in 153 (81.8%) lesions. The mean size of the lesions was 2.6 (standard
      deviation, 1.8) cm. The 30-day morbidity rate was 14.4%, and perforations and
      severe bleeding occurred in 4.3% and 3.2% of the patients, respectively. Among
      patients who had dysplasia or carcinoma, R0 resection was achieved in 78% and the
      piecemeal resection rate was 11.8%. Lateral margin involvement was 14% and
      vertical margin involvement was 8%. Local recurrence occurred in 9% of patients
      and 15% had residual disease. The 2-year overall survival rate and disease
      specific survival rate was 90.6% and 100%, respectively. CONCLUSION: Endoscopic
      mucosal resection and endoscopic submucosal dissection were introduced in low-to
      moderate-volume hospitals with acceptable morbidity rates. The short-term
      survival was excellent. However, other oncological outcomes were higher than
      those observed in high-volume centres and more secondary procedures were
      required.

PMID- 25999033
TI  - Translating evidence into practice: Hong Kong Reference Framework for Preventive
      Care for Children in Primary Care Settings.
AB  - There is increasing evidence that supports the close relationship between
      childhood and adult health. Fostering healthy growth and development of children
      deserves attention and effort. The Reference Framework for Preventive Care for
      Children in Primary Care Settings has been published by the Task Force on
      Conceptual Model and Preventive Protocols under the direction of the Working
      Group on Primary Care. It aims to promote health and prevent disease in children
      and is based on the latest research, and contributions of the Clinical Advisory
      Group that comprises primary care physicians, paediatricians, allied health
      professionals, and patient groups. This article highlights the comprehensive,
      continuing, and patient-centred preventive care for children and discusses how
      primary care physicians can incorporate the evidence-based recommendations into
      clinical practice. It is anticipated that the adoption of this framework will
      contribute to improved health and wellbeing of children. 

PMID- 25999032
TI  - Double balloon catheter for induction of labour in Chinese women with previous
      caesarean section: one-year experience and literature review.
AB  - OBJECTIVES: To evaluate the efficacy and safety of double balloon catheter for
      induction of labour in Chinese women with one previous caesarean section and
      unfavourable cervix at term. DESIGN: Retrospective cohort study. SETTING: A
      regional hospital in Hong Kong. PATIENTS: Women with previous caesarean delivery
      requiring induction of labour at term and with an unfavourable cervix from May
      2013 to April 2014. MAJOR OUTCOME MEASURES: Primary outcome was to assess rate of
      successful vaginal delivery (spontaneous or instrument-assisted) using double
      balloon catheter. Secondary outcomes were double balloon catheter induction-to
      delivery and removal-to-delivery interval; cervical score improvement; oxytocin
      augmentation; maternal or fetal complications during cervical ripening,
      intrapartum and postpartum period; and risk factors associated with unsuccessful
      induction. RESULTS: All 24 Chinese women tolerated double balloon catheter well.
      After double balloon catheter expulsion or removal, the cervix successfully
      ripened in 18 (75%) cases. The improvement in Bishop score 3 (interquartile
      range, 2-4) was statistically significant (P<0.001). Overall, 18 (75%) cases were
      delivered vaginally. The median insertion-to-delivery and removal-to-delivery
      intervals were 19 (interquartile range, 13.4-23.0) hours and 6.9 (interquartile
      range, 4.1-10.8) hours, respectively. Compared with cases without, the interval
      to delivery was statistically significantly shorter in those with spontaneous
      balloon expulsion or spontaneous membrane rupture during ripening (7.8 vs 3.0
      hours; P=0.025). There were no major maternal or neonatal complications. The only
      factor significantly associated with failed vaginal birth after caesarean was
      previous caesarean section for failure to progress (P<0.001). CONCLUSIONS: This
      is the first study using double balloon catheter for induction of labour in Asian
      Chinese women with previous caesarean section. Using double balloon catheter, we
      achieved a vaginal birth after caesarean rate of 75% without major complications.

PMID- 25999034
TI  - Oxidant and antioxidant status in neonatal proven and clinical sepsis according
      to selenium status.
AB  - BACKGROUND: Selenium is a trace element required for the functioning of the
      immune system. Neonatal sepsis is a serious condition leading to morbidity and
      mortality in neonates worldwide. The purpose of this study was to measure
      selenium and plasma selenoprotein P (SePP), selenoenzyme activity, and
      alterations in oxidant/antioxidant status with immune biomarkers in neonates with
      clinical (n = 27) and proven neonatal sepsis (n = 25). METHODS: Erythrocyte
      selenium and SePP; plasma lipid peroxidation (LP), protein oxidation and total
      antioxidant capacity and erythrocyte total glutathione (GSH) concentration;
      erythrocyte glutathione peroxidase (GPx), thioredoxin reductase (TrxR), catalase
      (CAT) and total superoxide dismutase (SOD) activity were measured
      spectrophotometrically/spectrofluorometrically. Plasma interleukin 2 and 6 were
      also measured. RESULTS: Erythrocyte selenium and SePP were markedly lower both in
      the clinical and proven sepsis groups versus control. Erythrocyte GPx activity
      was higher only in the clinical sepsis group. TrxR activity was markedly lower in
      proven sepsis. SOD activity and GSH were markedly higher both in clinical sepsis
      and in proven sepsis. CAT activity was significantly higher both in clinical
      sepsis and in proven sepsis. LP and protein oxidation were significantly higher
      in both of the sepsis groups. CONCLUSIONS: Both selenium-dependent and selenium
      independent blood redox systems were altered in sepsis, suggesting that sepsis
      causes an imbalance between cellular antioxidant and oxidant states.

PMID- 25999035
TI  - A shortcut to high-affinity Ga-68 and Cu-64 radiopharmaceuticals: one-pot click
      chemistry trimerisation on the TRAP platform.
AB  - Due to its 3 carbonic acid groups being available for bioconjugation, the TRAP
      chelator (1,4,7-triazacyclononane-1,4,7-tris(methylene(2-carboxyethylphosphinic
      acid))) is chosen for the synthesis of trimeric bioconjugates for radiolabelling.
      We optimized a protocol for bio-orthogonal TRAP conjugation via Cu(I)-catalyzed
      Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), including a
      detailed investigation of kinetic properties of Cu(II)-TRAP complexes. TRAP
      building blocks for CuAAC, TRAP(alkyne)3 and TRAP(azide)3 were obtained by amide
      coupling of propargylamine/3-azidopropyl-1-amine, respectively. For Cu(II)
      complexes of neat and triply amide-functionalized TRAP, the equilibrium
      properties as well as pseudo-first-order Cu(II)-transchelation, using 10 to 30
      eq. of NOTA and EDTA, were studied by UV-spectrophotometry. Dissociation of any
      Cu(II)-TRAP species was found to be independent on the nature or excess of a
      competing chelator, confirming a proton-driven two-step mechanism. The respective
      thermodynamic stability constants (log K(ML): 19.1 and 17.6) and dissociation
      rates (k: 38 * 10(-6) and 7 * 10(-6) s(-1), 298 K, pH 4) show that the Cu(II)
      complex of the TRAP-conjugate possesses lower thermodynamic stability but higher
      kinetic inertness. At pH 2-3, its demetallation with NOTA was complete within
      several hours/days at room temperature, respectively, enabling facile Cu(II)
      removal after click coupling by direct addition of NOTA trihydrochloride to the
      CuAAC reaction mixture. Notwithstanding this, an extrapolated dissociation half
      life of >100 h at 37  degrees C and pH 7 confirms the suitability of TRAP
      bioconjugates for application in Cu-64 PET (cf. t(1/2)(Cu-64) = 12.7 h). To
      showcase advantages of the method, TRAP(DUPA-Pep)3, a trimer of the PSMA
      inhibitor DUPA-Pep, was synthesized using 1 eq. TRAP(alkyne)3, 3.3 eq. DUPA-Pep
      azide, 10 eq. Na ascorbate, and 1.2 eq. Cu(II)-acetate. Its PSMA affinity (IC50),
      determined by the competition assay on LNCaP cells, was 18-times higher than that
      of the corresponding DOTAGA monomer (IC50: 2 +/- 0.1 vs. 36 +/- 4 nM), resulting
      in markedly improved contrast in Ga-68-PET imaging. In conclusion, the kinetic
      inertness profile of Cu(II)-TRAP conjugates allows for simple Cu(II) removal
      after click functionalisation by means of transchelation, but also confirms their
      suitability for Cu-64-PET as demonstrated previously (Dalton Trans., 2012, 41,
      13803).

PMID- 25999036
TI  - Oxygen transfer coefficient and the kinetic parameters of exo-polygalacturonase
      production by Aspergillus flavipes FP-500 in shake flasks and bioreactor.
AB  - AIMS: To evaluate and compare the sensitivity of Exo-PG production and kinetic
      parameters of Aspergillus flavipes FP-500 to oxygen transfer condition in shake
      flasks and bioreactor. METHODS AND RESULTS: Aspergillus flavipes FP-500 was grown
      on pectin as carbon source in shake flasks and bioreactor at different oxygen
      transfer conditions. The volumetric coefficient of oxygen transfer (kLa) was
      modified by changing both, the flask size/medium volume ratio and the agitation
      speed. Higher biomass concentration, Exo-PG activity, maximum specific growth
      rate and yield coefficient were obtained in bioreactor at higher kLa value. A
      strong correlation was found between biomass, Exo-PG activity and growth
      associated product coefficient to kLa in bioreactor but does not in shake flasks.
      The mathematical model provided a good description of growth, pectin consumption
      and Exo-PG production in submerged batch cultures carried out in bioreactor.
      CONCLUSIONS: Biomass concentration, Exo-PG activity and their kinetics of
      Aspergillus flavipes FP-500 were strongly influenced by oxygen transfer condition
      and cultivation system. Significance and Impact of Study The production of
      enzymes by fungal fermentation is strictly aerobic and understanding the
      influence of oxygen transfer condition on the production kinetic is of vital
      importance in order to design, optimize and translate bioprocesses to industrial
      scale.

PMID- 25999037
TI  - Regulated intramembrane proteolysis of the virulence activator TcpP in Vibrio
      cholerae is initiated by the tail-specific protease (Tsp).
AB  - Vibrio cholerae uses a multiprotein transcriptional regulatory cascade to control
      expression of virulence factors cholera toxin and toxin-co-regulated pilus. Two
      proteins in this cascade are ToxR and TcpP - unusual membrane-localized
      transcription factors with relatively undefined periplasmic domains and
      transcription activator cytoplasmic domains. TcpP and ToxR function with each
      other and two other membrane-localized proteins, TcpH and ToxS, to activate
      transcription of toxT, encoding the direct activator of toxin and pilus genes.
      Under some conditions, TcpP is degraded in a two-step proteolytic pathway known
      as regulated intramembrane proteolysis (RIP), thereby inactivating the cascade.
      The second step in this proteolytic pathway involves the zinc metalloprotease
      YaeL; V. cholerae cells lacking YaeL accumulate a truncated yet active form of
      TcpP termed TcpP*. We hypothesized that a protease acting prior to YaeL degrades
      TcpP to TcpP*, which is the substrate of YaeL. In this study, we demonstrate that
      a C-terminal protease called Tsp degrades TcpP to form TcpP*, which is then acted
      upon by YaeL. We present evidence that TcpH and Tsp serve to protect full-length
      TcpP from spurious proteolysis by YaeL. Cleavage by Tsp occurs in the periplasmic
      domain of TcpP and requires residues TcpPA172 and TcpPI174 for wild-type
      activity. 

PMID- 25999038
TI  - Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to
      Transcatheter Arterial Chemoembolization.
AB  - BACKGROUND/AIM: We examined tumor marker levels to assess in more detail
      transcatheter arterial chemoembolization (TACE)-refractory hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: We enrolled patients treated from 2000 to
      2011 for HCC beyond the Milan criteria who had good hepatic reserve function
      (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The
      modified criteria for being TACE-refractory according to the Liver Cancer Study
      Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the
      Assessment for Retreatment with TACE (ART) score were used for determining
      whether the HCC was TACE refractory. alpha-Fetoprotein >= 100 ng/ml, fucosylated
      alpha-fetoprotein >= 10%, and des-gamma-carboxy prothrombin >= 100 mAU/ml were
      used to define whether tumor markers were positive. We added up the number of
      positive tumor markers as a prognostic score to assess in more detail the
      evaluation of TACE-refractory HCC. RESULTS: In order to divide the patients into
      a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time
      (MST) 27.1 vs. 49.9 months; p < 0.001] were superior to the ART score (MST 22.0
      vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ
      criteria, the patients with a low score of positive tumor markers (<2) after 2
      sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST
      37.7 vs. 23.2 months; p = 0.014). CONCLUSION: Patients being nonrefractory
      according to the m-LCSGJ criteria had a better response, and using the number of
      tumor markers (>= 2) is an easy method for predicting the response to TACE and
      for a more detailed evaluation of TACE-refractory HCC.

PMID- 25999039
TI  - Modulation of motivational salience processing during the early stages of
      psychosis.
AB  - BACKGROUND: Deficits in motivational salience processing have been related to
      psychotic symptoms and disturbances in dopaminergic neurotransmission. We aimed
      at exploring changes in salience processing and brain activity during different
      stages of psychosis and antipsychotic medication effect. METHODS: We used fMRI
      during the Salience Attribution Task to investigate hemodynamic differences
      between 19 healthy controls (HCs), 34 at-risk mental state (ARMS) individuals and
      29 individuals with first-episode psychosis (FEP), including a subgroup of 17 FEP
      without antipsychotic medication (FEP-UM) and 12 FEP with antipsychotic
      medication (FEP-M). Motivational salience processing was operationalized by brain
      activity in response to high-probability rewarding cues (adaptive salience) and
      in response to low-probability rewarding cues (aberrant salience). RESULTS:
      Behaviorally, adaptive salience response was not accelerated in FEP, although
      they correctly distinguished between trials with low and high reward probability.
      In comparison to HC, ARMS exhibited a lower hemodynamic response during adaptive
      salience in the right inferior parietal lobule and FEP-UM in the left dorsal
      cingulate gyrus. The FEP-M group exhibited a lower adaptive salience response
      than HC in the right insula and than ARMS in the anterior cingulate gyrus. In
      unmedicated individuals, the severity of hallucinations and delusions correlated
      negatively with the insular- and anterior cingulate hemodynamic response during
      adaptive salience. We found no differences in aberrant salience processing
      associated with behavior or medication. CONCLUSION: The changes in adaptive
      motivational salience processing during psychosis development reveal
      neurofunctional abnormalities in the somatosensory and premotor cortex.
      Antipsychotic medication seems to modify hemodynamic responses in the anterior
      cingulate and insula.

PMID- 25999041
TI  - Reduced sleep spindle density in early onset schizophrenia: a preliminary
      finding.

PMID- 25999040
TI  - Demographic correlates of attenuated positive psychotic symptoms.
AB  - It is now well established that the utilization of standardized clinical criteria
      can enhance prediction of psychosis. These criteria are primarily concerned with
      the presence and severity of attenuated positive symptoms. Because these symptom
      criteria are used to derive algorithms for designating clinical high risk (CHR)
      status and for maximizing prediction of psychosis risk, it is important to know
      whether the symptom ratings vary as a function of demographic factors that have
      previously been linked with symptoms in diagnosed psychotic patients. Using a
      sample of 356 CHR individuals from the NAPLS-II multi-site study, we examined the
      relation of three sex, age, and educational level, with the severity of
      attenuated positive symptom scores from the Scale of Prodromal Symptoms (SOPS).
      Demographic factors accounted for little of the variance in symptom ratings (5
      6%). Older CHR individuals manifested more severe suspiciousness, and female CHR
      participants reported more unusual perceptual experiences than male participants.
      Contrary to prediction, higher educational level was associated with more severe
      ratings of unusual thought content, but less severe perceptual abnormalities.
      Overall, sex, age and education were modestly related to unusual thought content
      and perceptual abnormalities, only, suggesting minimal implication for
      designating CHR status and predicting psychosis-risk.

PMID- 25999043
TI  - A systematic review and meta-analysis of the effect of depot antipsychotic
      frequency on compliance and outcome.
AB  - BACKGROUND: Depot antipsychotics are commonly used to improve adherence and
      clinical outcomes such as relapse and readmission. Dosing regimens vary but are
      commonly two- and four-weekly. To date, the effect of administration at two
      weekly or four-weekly intervals on outcome has not been examined in a meta
      analysis. AIMS: A systematic review and meta-analysis on whether the frequency of
      depot antipsychotic administration (e.g., two- vs four-weekly) makes any
      difference to compliance and outcome. METHODS: A systematic search of Medline,
      EMBASE and PsycInfo for RCTs that compared the frequency of depot administration
      (e.g., two- vs four-weekly) for an equivalent dose. Outcomes were compliance,
      psychiatric symptomatology, quality of life, adverse drug reactions (ADRs),
      patient preference, admission rates, bed-days and costs. RESULTS: Seven studies
      from eight papers (n=3994) were found covering olanzapine, paliperidone,
      risperidone, haloperidol and fluphenazine enanthate/decanoate with follow-up of
      up to one year. Meta-analyses were possible for psychotic symptoms and ADRs.
      There were no differences in psychotic symptoms or quality of life between two-
      and four-weekly doses. Health service use was not reported. For ADRs, the only
      significant difference detected was that two-weekly injections were less likely
      to lead to site pain (RR 0.16, 95% CI 0.07-0.38; 2 studies n=1667). There were no
      differences in other ADRs. CONCLUSIONS: There were surprisingly little data on
      the effect of dosing frequency for an equivalent dose on clinical outcomes. There
      is a need for long-term studies of a wide range of outcomes including cost
      effectiveness. Claims for advantages of new preparations over others require
      careful evaluation.

PMID- 25999044
TI  - Effect of in vitro and in vivo conditions on development of parthenogenetic
      rabbit embryos after vitrification.
AB  - Parthenote embryos offer multiple opportunities in biotechnological research, so
      it is important to analyse the possibilities for their cryopreservation in order
      to establish a biobank. The aim of this experiment was to determine the effect of
      culture conditions and vitrification on rabbit parthenogenetic embryos.
      Parthenotes were cultured under in vivo and in vitro conditions until day 3 (late
      morula/early blastocyst), when they were vitrified. Immediately after warming,
      they were newly cultured under in vivo and in vitro conditions till day 6
      (blastocyst stage). Both culture conditions showed similar late morula/early
      blastocyst (0.39+/-0.056 vs. 0.46+/-0.043, for in vivo and in vitro,
      respectively) and blastocyst rates (0.12+/-0.068 vs. 0.13+/-0.070, for in vivo
      and in vitro, respectively). However, no parthenote was recovered when a
      combination of culture conditions was performed. To our best knowledge, this is
      the first demonstration of the ability of rabbit parthenogenetic embryos to
      develop after vitrification, with similar embryo development after in vivo or in
      vitro culture. Nevertheless, our results highlight the importance of culture
      conditions on the morphology of parthenote embryos. Therefore, we have described
      that special attention should be paid on culture conditions to generate
      parthenote embryos, with a view to their subsequent use, for example in embryonic
      stem cell production. 

PMID- 25999042
TI  - Targeting neurosteroid synthesis as a therapy for schizophrenia-related
      alterations induced by early psychosocial stress.
AB  - BACKGROUND: Cogent evidence has shown that schizophrenia vulnerability is
      enhanced by psychosocial stress in adolescence, yet the underpinnings of this
      phenomenon remain elusive. One of the animal models that best capture the
      relationship between juvenile stress and schizophrenia is isolation rearing (IR).
      This manipulation, which consists in subjecting rats to social isolation from
      weaning through adulthood, results in neurobehavioral alterations akin to those
      observed in schizophrenia patients. In particular, IR-subjected rats display a
      marked reduction of the prepulse inhibition (PPI) of the startle reflex, which
      are posited to reflect imbalances in dopamine neurotransmission in the nucleus
      accumbens (NAcc). We recently documented that the key neurosteroidogenic enzyme
      5alpha-reductase (5alphaR) plays an important role in the dopaminergic regulation
      of PPI; given that IR leads to a marked down-regulation of this enzyme in the
      NAcc, the present study was designed to further elucidate the functional role of
      5alphaR in the regulation of PPI of IR-subjected rats. METHODS: We studied the
      impact of the prototypical 5alphaR inhibitor finasteride (FIN) on the PPI
      deficits and NAcc steroid profile of IR-subjected male rats, in comparison with
      socially reared (SR) controls. RESULTS: FIN (25-100 mg/kg, i.p.) dose-dependently
      countered IR-induced PPI reduction, without affecting gating integrity in SR
      rats. The NAcc and striatum of IR-subjected rats displayed several changes in
      neuroactive steroid profile, including a reduction in pregnenolone in both SR and
      IR-subjected groups, as well as a decrease in allopregnanolone content in the
      latter group; both effects were significantly opposed by FIN. CONCLUSIONS: These
      results show that 5alphaR inhibition counters the PPI deficits induced by IR,
      possibly through limbic changes in pregnenolone and/or allopregnanolone
      concentrations.

PMID- 25999045
TI  - Visual exposure to obesity: Experimental effects on attraction toward overweight
      men and mate choice in females.
AB  - BACKGROUND: Cultural differences in ideal body weight are well established, but
      less research has examined attraction toward potential mates of heavier body
      weights. We examined whether exposure to obesity increases physical attraction
      toward overweight men. METHODS: In Studies 1 and 2, we examined the effect that
      exposure to obese vs healthy weight men had on female attraction toward an
      overweight man. Study 3 examined whether females who are regularly exposed to
      males of heavier body weights reported a greater attraction toward overweight
      men. Study 4 tested whether females in an online dating study were more likely to
      choose to date an overweight man, after having been exposed to obesity. RESULTS:
      Exposure to obesity altered visual perceptions of what normal and therefore
      healthy body weights were and this resulted in greater attraction toward an
      overweight man (Studies 1 and 2). Females regularly exposed to men of heavier
      body weight reported a greater attraction toward overweight men (Study 3). After
      exposure to obesity, females in an online dating study were more likely to choose
      to date an overweight man ahead of a healthy weight man (Study 4). CONCLUSIONS:
      Exposure to male obesity increases female attraction toward overweight men and
      may affect mate choice.

PMID- 25999047
TI  - Interferon-inducible cholesterol-25-hydroxylase restricts hepatitis C virus
      replication through blockage of membranous web formation.
AB  - Hepatitis C virus (HCV) is a positive-strand RNA virus that primarily infects
      human hepatocytes. Infections with HCV constitute a global health problem, with
      180 million people currently chronically infected. Recent studies have reported
      that cholesterol 25-hydroxylase (CH25H) is expressed as an interferon-stimulated
      gene and mediates antiviral activities against different enveloped viruses
      through the production of 25-hydroxycholesterol (25HC). However, the intrinsic
      regulation of human CH25H (hCH25H) expression within the liver as well as its
      mechanistic effects on HCV infectivity remain elusive. In this study, we
      characterized the expression of hCH25H using liver biopsies and primary human
      hepatocytes. In addition, the antiviral properties of this protein and its
      enzymatic product, 25HC, were further characterized against HCV in tissue
      culture. Levels of hCH25H messenger RNA were significantly up-regulated both in
      HCV-positive liver biopsies and in HCV-infected primary human hepatocytes. The
      expression of hCH25H in primary human hepatocytes was primarily and transiently
      induced by type I interferon. Transient expression of hCH25H in human hepatoma
      cells restricted HCV infection in a genotype-independent manner. This inhibition
      required the enzymatic activity of CH25H. We observed an inhibition of viral
      membrane fusion during the entry process by 25HC, which was not due to a
      virucidal effect. Yet the primary effect by 25HC on HCV was at the level of RNA
      replication, which was observed using subgenomic replicons of two different
      genotypes. Further analysis using electron microscopy revealed that 25HC
      inhibited formation of the membranous web, the HCV replication factory,
      independent of RNA replication. CONCLUSION: Infection with HCV causes up
      regulation of interferon-inducible CH25H in vivo, and its product, 25HC,
      restricts HCV primarily at the level of RNA replication by preventing formation
      of the viral replication factory.

PMID- 25999046
TI  - MiR-26b modulates insulin sensitivity in adipocytes by interrupting the
      PTEN/PI3K/AKT pathway.
AB  - BACKGROUND: MicroRNAs (miRNAs) have emerged as epigenetic regulators of
      metabolism and energy homeostasis. There is a growing body of evidence pointing
      to miRNAs that have important regulatory roles in insulin sensitivity. OBJECTIVE:
      The aim of this work was to explore the expression and mechanism of action of miR
      26b in obesity-related insulin resistance (IR) in adipocytes. METHODS:
      Quantitative real-time PCR was performed to determine miR-26b expression in obese
      rodent models, human obesity subjects and insulin-resistant adipocytes. We
      analysed the roles of miR-26b overexpression and inhibition on glucose uptake in
      adipocytes. Western blotting was used to detect the levels of protein molecules
      involved in the phosphoinositide-3-kinase (PI3K) pathway. Bioinformatics and the
      Dual Luciferase Assay were used to identify the target gene of miR-26b. We
      assessed the regulatory roles of miR-26b on the phosphatase and tensin homologue
      (PTEN)/PI3K/AKT pathway and the relationship between miR-26b and the metabolism
      of human obese subjects. RESULTS: Levels of miR-26b are reduced in visceral
      adipose tissue (VAT) in obese rodent models, human obesity and insulin-resistant
      adipocytes. MiR-26b promotes insulin-stimulated glucose uptake and increases
      insulin-stimulated glucose transporter type 4 translocation to the plasma
      membrane in human mature adipocytes. MiR-26b modulates insulin-stimulated AKT
      activation via inhibition of its target gene, PTEN, and significantly increases
      insulin sensitivity via the PTEN/PI3K/AKT pathway. The expression level of miR
      26b negatively correlates with increasing body mass index and homeostasis model
      assessment for IR in human obese subjects. CONCLUSION: Decreased miR-26b
      expression in VAT may be involved in obesity-related IR by interrupting the
      PTEN/PI3K/AKT pathway.

PMID- 25999048
TI  - Ontogenetic variation in the body stoichiometry of two fish species.
AB  - One of the central questions of ecological stoichiometry theory is to what extent
      animal species maintain constant elemental composition in their bodies. Although
      several recent studies demonstrate intraspecific variation in animal elemental
      composition, relatively little is known about ontogenetic changes in vertebrates,
      especially during early life stages. We studied the intraspecific and
      interspecific ontogenetic variation in the body stoichiometry of two fish species
      in two different orders; fathead minnow (Pimephales promelas) and sheepshead
      minnow (Cyprinodon variegatus), reared under controlled laboratory conditions.
      During ontogeny, we measured the chemical composition of fish bodies, including
      carbon (C), nitrogen (N), phosphorus (P), calcium (Ca), and ribonucleic acid
      (RNA) contents. We found that N and RNA contents were relatively high in early
      life stages and declined substantially during development. In contrast, body C
      and C:N ratios were relatively low in embryos, post-embryos and larvae, and
      increased remarkably thereafter. Concentrations and ratios of some elements
      (e.g., Ca, P, Ca:P) did not exhibit consistent ontogenetic trends, but fluctuated
      dynamically between consecutive developmental stages in both species. Specific
      growth rates correlated significantly with RNA contents in both species. Analyses
      of the relative importance of different P pools at each developmental stage
      revealed that RNA was a considerable P pool in post-embryos, while bone
      associated P was the dominant body P pool in later stages. Our results suggest
      that the elemental composition of fish bodies changes considerably during
      ontogeny. Each ontogenetic stage has its own stoichiometric signature, but the
      timing, magnitude and direction of ontogenetic changes can vary substantially
      between taxa.

PMID- 25999050
TI  - Attacks on mental health care institutions seen as symbol of Westernization:
      Lessons from history of psychiatry?

PMID- 25999049
TI  - Screening of aptamers specific to colorectal cancer cells and stem cells by
      utilizing On-chip Cell-SELEX.
AB  - Colorectal cancer (CRC) is the most frequently diagnosed cancer around the world,
      causing about 700,000 deaths every year. It is clear now that a small fraction of
      CRC, named colorectal cancer stem cells (CSCs) exhibiting self-renewal and
      extensive proliferative activities, are hard to be eradicated. Unfortunately,
      highly specific biomarkers for colorectal CSC (CR-CSCs) are lacking that
      prohibits the development of effective therapeutic strategies. This study
      designed and manufactured a novel microfluidic system capable of performing a
      fully automated cell-based, systematic evolution of ligands by exponential
      enrichment (SELEX) process. Eight CR-CSC/CRC-specific aptamers were successfully
      selected using the microfluidic chip. Three of the aptamers showed high
      affinities towards their respective target cells with a dissociation constant of
      27.4, 28.5 and 12.3 nM, which are comparable to that of antibodies.

PMID- 25999051
TI  - Analysis of RAS mutation and PAX8/PPARgamma rearrangements in follicular-derived
      thyroid neoplasms in a Korean population: frequency and ultrasound findings.
AB  - OBJECTIVE: To investigate the frequency and ultrasonography (US) findings of RAS
      mutations and PAX8/PPARgamma rearrangements between follicular thyroid adenomas
      (FTAs) and follicular thyroid carcinomas (FTCs) in a Korean population. METHODS:
      RAS mutations and PAX8/PPARgamma rearrangements in 56 FTAs and 35 FTCs were
      analyzed. We also analyzed the US findings of FTCs and FTAs. RESULTS: 16 nodules
      of 35 FTCs (45.7 %) and 19 nodules of 56 FTAs (33.9 %) harbored RAS mutations.
      Three FTCs and three FTAs showed two point mutations simultaneously. K-RAS codon
      12-13 (n = 6, 31.6 %), N-RAS codon 61 (n = 5, 26.3 %), H-RAS codon 61 (n = 4,
      21.1 %), K-RAS codon 61 (n = 3, 15.8 %), and N-RAS codon 12-13 (n = 1, 5.3 %)
      were found in FTCs, and N-RAS codon 61 (n = 10, 45 %), K-RAS codon 12-13 (n = 5,
      22.7 %), H-RAS codon 61 (n = 5, 22.7 %), K-RAS codon 61 (n = 1, 4.5 %), and N-RAS
      codon 12-13 (n = 1, 4.5 %) were observed in FTAs. 4 of 56 (7.1 %) FTAs and 1 of
      35 (2.9 %) FTCs represented PAX8/PPARgamma rearrangements, respectively (P =
      0.645). The absence of a hypoechoic rim (P = 0.021) and presence of
      calcifications (P = 0.049) were significantly associated with FTCs compared with
      FTAs. CONCLUSIONS: RAS mutation frequency targeting the Korean population showed
      a 45.7 % in FTCs and 35.7 % in FTAs, and PAX8/PPARgamma rearrangements were more
      frequently showed in FTAs. K-RAS codon 12-13 was the most common RAS mutation in
      FTCs, whereas N-RAS codon 61 was more frequent in FTAs. The presence of
      calcifications and absence of a hypoechoic rim showed more frequently in FTCs.

PMID- 25999052
TI  - Cochlear implantation in children with single-sided deafness: does aetiology and
      duration of deafness matter?
AB  - For adult patients with single-sided deafness (SSD), treatment with a cochlear
      implant (CI) is well established as an acceptable and beneficial hearing
      rehabilitation method administered routinely in clinical practice. In contrast,
      for children with SSD, CI has been applied less often to date, with the rationale
      to decide either on a case-by-case basis or under the realm of clinical research.
      The aim of our clinical study was to evaluate the longitudinal benefits of CI for
      a group of children diagnosed with SSD and to compare their outcomes with respect
      to patient characteristics. Evaluating a pool of paediatric SSD patients
      presenting for possible CI surgery revealed that the primary aetiology of
      deafness was congenital cochlear nerve deficiency. A subgroup of children meeting
      the CI candidacy criteria for the affected ear (the majority with acquired
      hearing loss) were enrolled in the study. Preliminary group results suggest
      substantial improvements in speech comprehension in noise and in the ability to
      localise sound, which was demonstrated through objective and subjective
      assessments after CI treatment for the group, with results varying from patient
      to patient. Our study shows a trend towards superior outcomes for children with
      acquired hearing loss and a shorter duration of hearing loss compared to
      congenitally deafened children who had a longer duration of SSD. This indicates
      an interactive influence of the age at onset, aetiology and duration of deafness
      upon the restoration of binaural integration and the overall benefits of sound
      stimulation to two ears after CI treatment. Continued longitudinal investigation
      of these children and further studies in larger groups may provide more guidance
      on the optimal timing of treatment for paediatric patients with acquired and
      congenital SSD.

PMID- 25999053
TI  - Daclatasvir, Simeprevir and Ribavirin as a Promising Interferon-Free Triple
      Regimen for HCV Recurrence after Liver Transplant.
AB  - BACKGROUND: Recurrent hepatitis C infection after liver transplantation (LT) is
      associated with lower rates of graft and patient survival. METHODS: Here we
      describe the first use of daclatasvir, simeprevir, and ribavirin (RBV) as an all
      oral triple regimen administered to 6 liver transplant recipients with recurrent
      hepatitis C, one with GT 1a and 5 with GT 1b. All patients were treated for 24
      weeks. Trough levels of immunosuppression, laboratory measures, and potential
      adverse effects were closely monitored. RESULTS: For all patients, viral load
      became undetectable between treatment weeks 4 and 12. One patient experienced a
      viral breakthrough at the 10th week of treatment; this was associated with the
      selection of resistance-associated variants (D168Y in NS3 and DeltaP32 in NS5A).
      For the other 5 patients, end-of-treatment response and for 4 patients SVR24 was
      achieved. Viremia recurred in one patient 4 weeks after the end of treatment,
      which was again associated with the selection of resistance-associated variants
      (D168V in NS3 and DeltaP32 in NS5A). Clinical measures of liver function improved
      substantially for all patients. Adverse events were few and limited to moderate
      anemia caused by RBV. Importantly, adjustments to the immunosuppressant dosage
      were not required. CONCLUSIONS: The described regimen appears to be safe and
      effective for liver transplant patients and will be a promising treatment regimen
      for post-LT patients.

PMID- 25999054
TI  - Phylogenomic analyses reveal subclass Scuticociliatia as the sister group of
      subclass Hymenostomatia within class Oligohymenophorea.
AB  - Scuticociliates and hymenostomes are two groups of the ciliate class
      Oligohymenophorea, a diverse clade that includes two model genera, Tetrahymena
      and Paramecium, which have been intensively studied due to their ease of culture
      and their amenability to a wide range of biochemical and genetic investigations.
      However, phylogenetic relationships among the subclasses of the
      Oligohymenophorea, and especially between the Scuticociliatia and Hymenostomatia,
      are not clearly resolved. Here, we investigate the phylogenetic relationship
      between the subclasses Scuticociliatia and Hymenostomatia based on omics data.
      The transcriptomes of five species, comprising four oligohymenophoreans and one
      colpodean, were sequenced. A supermatrix was constructed for phylogenomic
      analyses based on 113 genes encoding 43,528 amino acid residues from 26 taxa,
      including ten representatives of the class Oligohymenophorea. Our phylogenomic
      analyses revealed that the monophyletic Scuticociliatia is sister to the
      monophyletic Hymenostomatia, which together form the terminal branch within the
      monophyletic class Oligohymenophorea. Competing hypotheses for this relationship
      were rejected by topological tests. Our results provide corroborative evidence
      for the close relationship between the subclasses Scuticociliatia and
      Hymenostomatia, justifying the possible use of the model hymenostome T.
      thermophila as an effective experimental system to study the molecular and
      cellular biology of the scuticociliates. 

PMID- 25999055
TI  - Horsetails are the sister group to all other monilophytes and Marattiales are
      sister to leptosporangiate ferns.
AB  - The "Monilophyte" clade comprising ferns, horsetails and whisk ferns receives
      unequivocal support from molecular data as the sister clade to seed plants.
      However, the branching order of its earliest emerging lineages, the Equisetales
      (horsetails), the Marattiales, the Ophioglossales/Psilotales and the large group
      of leptosporangiate ferns has remained dubious. We investigated the mitochondrial
      nad2 and rpl2 genes as two new, intron-containing loci for a wide sampling of
      taxa. We found that both group II introns - nad2i542g2 and rpl2i846g2 - are
      universally present among monilophytes. Both introns have orthologues in seed
      plants where nad2i542g2 has evolved into a trans-arrangement. In contrast and
      despite substantial size extensions to more than 5kb in Psilotum, nad2i542g2
      remains cis-arranged in the monilophytes. For phylogenetic analyses, we filled
      taxonomic gaps in previously investigated mitochondrial (atp1, nad5) and
      chloroplast (atpA, atpB, matK, rbcL, rps4) loci and created a 9-gene matrix that
      also included the new mitochondrial nad2 and rpl2 loci. We extended the taxon
      sampling with two taxa each for all land plant outgroups (liverworts, mosses,
      hornworts, lycophytes and seed plants) to minimize the risk of phylogenetic
      artefacts. We ultimately obtained a well-supported molecular phylogeny placing
      Marattiales as sister to leptosporangiate ferns and horsetails as sister to all
      remaining monilophytes. In addition, an indel in an exon of the here introduced
      rpl2 locus independently supports the placement of horsetails. We conclude that
      under dense taxon sampling, phylogenetic information from a prudent choice of
      loci is currently superior to character-rich phylogenomic approaches at low taxon
      sampling. As here shown the selective choice of loci and taxa enabled us to
      resolve the long-enigmatic diversifications of the earliest monilophyte lineages.

PMID- 25999056
TI  - Inhibition of Heat-Stable Toxin-Induced Intestinal Salt and Water Secretion by a
      Novel Class of Guanylyl Cyclase C Inhibitors.
AB  - BACKGROUND: Many enterotoxigenic Escherichia coli strains produce the heat-stable
      toxin, STa, which, by activation of the intestinal receptor-enzyme guanylyl
      cyclase (GC) C, triggers an acute, watery diarrhea. We set out to identify GCC
      inhibitors that may be of benefit for the treatment of infectious diarrheal
      disease. METHODS: Compounds that inhibit STa-induced cyclic guanosine 3',5'
      monophosphate (cGMP) production were selected by performing cyclase assays on
      cells and membranes containing GCC, or the related GCA. The effect of leads on
      STa/GCC-dependent activation of the cystic fibrosis transmembrane conductance
      regulator anion channel was investigated in T84 cells, and in porcine and human
      intestinal tissue. Their effect on STa-provoked fluid transport was assessed in
      ligated intestinal loops in piglets. RESULTS: Four N-2-(propylamino)-6
      phenylpyrimidin-4-one-substituted piperidines were shown to inhibit GCC-mediated
      cellular cGMP production. The half maximal inhibitory concentrations were <= 5 *
      10(-7) mol/L, whereas they were >10 times higher for GCA. In T84 monolayers,
      these leads blocked STa/GCC-dependent, but not forskolin/adenylyl cyclase
      dependent, cystic fibrosis transmembrane conductance regulator activity. GCC
      inhibition reduced STa-provoked anion secretion in pig jejunal tissue, and fluid
      retention and cGMP levels in STa-exposed loops. These GCC inhibitors blocked STa
      provoked anion secretion in rectal biopsy specimens. CONCLUSIONS: We have
      identified a novel class of GCC inhibitors that may form the basis for
      development of future therapeutics for (infectious) diarrheal disease.

PMID- 25999057
TI  - Development and Characterization of Broadly Cross-reactive Monoclonal Antibodies
      Against All Known Ebolavirus Species.
AB  - As of 25 March 2015, the largest recorded outbreak of Ebola virus infection is
      ongoing, with almost 25 000 cases and >10 000 deaths. There are 5 genetically and
      antigenically distinct species within the genus Ebolavirus. Limited cross
      reactivity and protection is observed between these 5 Ebolavirus species, which
      complicates vaccine development. However, on the basis of sequence homology
      between the 5 Ebolavirus species, we hypothesize that conserved epitopes are
      present on the viral glycoprotein (GP), which can be targeted by antibodies. In
      the current study, a panel of mouse monoclonal antibodies was isolated and
      characterized using an enzyme-linked immunosorbent assay (ELISA) to determine
      cross-reactivity, avidity, and competition for epitope binding; Western blot
      analysis was also performed. Four monoclonal antibodies were identified by ELISA
      as cross-reacting with the GPs of all 5 Ebolavirus species. The identification of
      cross-reactive antibodies that bind the GPs of all known Ebolavirus species will
      give us important insight into the presence of conserved epitopes on the viral
      GP. These data will be crucial for the development of novel therapeutics and
      diagnostic assays. 

PMID- 25999058
TI  - Description of Ophthalmic Pharmaceutical and Device Start-Up Companies.
AB  - AIMS: To describe the number, type and location of ophthalmic companies and their
      associated product areas and indications. METHODS: A retrospective, non-patient
      based, observational review of ophthalmic pharmaceutical and device companies
      with a new product in development. Data was compiled by Internet searches.
      RESULTS: We identified 190 companies currently developing ophthalmic products:
      134 (71%) were privately held and 56 (29%) publicly held, while 136 (72%) were in
      the United States and 53 (28%) were outside the United States. There were 436
      total products of which 338 (78%) were pharmaceuticals and 98 (22%) devices. With
      pharmaceuticals we identified 46 separate indications with age-related macular
      degeneration (n = 75), glaucoma (n = 52) and dry eye (n = 46) as most common;
      anti-vascular endothelial growth factor, hormone therapy and anti-inflammatory
      products were also common classes. With devices there were 30 indications with
      glaucoma (n = 26), age-related macular degeneration (n = 19) and dry eye (n = 6)
      as most common; drug delivery, ocular implants and prostheses were less common
      classes. CONCLUSIONS: Ophthalmology as a specialty is benefited by a wide effort
      in new medicine and device development. However, a concentration of effort into
      relatively few indications suggests a potential lack of market analysis and
      possible difficulty for many companies in commercializing their product.

PMID- 25999059
TI  - Defining a medication class as a teratogen: may the evidence be with you and not
      the FDA Pregnancy Risk Categories.

PMID- 25999060
TI  - Post-translational modifications: A chromosome's guide to the spindle equator.

PMID- 25999061
TI  - Nuclear envelope: Curving out a nuclear pore.

PMID- 25999063
TI  - Parameters used to discontinue dialysis in acute kidney injury recovery: a survey
      of United States nephrologists.
AB  - BACKGROUND: Despite advances in the approach to cure acute kidney injury (AKI),
      including definition, classification and treatment methods, there are no standard
      criteria to withdraw dialysis in the setting of improving AKI. We conducted this
      survey to elucidate parameters that United States (US) nephrologists used to
      determine when to stop dialysis with improving renal function in AKI. We
      hypothesized that there would be a difference in approach to weaning a patient
      off dialysis based on years in practice or the number of cases of AKI treated per
      year. METHODS: This was an anonymous electronic survey of practicing
      nephrologists who treated AKI. Data was de-identified and analyzed using
      descriptive statistics. RESULTS: The commonest criteria used to stop dialysis
      when renal function improved was, in decreasing order of importance, resolution
      in oliguria (51%), resolution of volume overload (29%), improvement in serum
      creatinine (26.7%) and resolution of hyperkalemia (21%). The most common reasons
      for re-starting dialysis within 28 days did not show a specific trend but
      respondents (20%) reported re-starting if estimated glomerular filtration rates
      (eGFR) declined. There was no significant pattern in approach to withdrawing
      dialysis or resuming dialysis based on the number of years in nephrology
      practice. However, responses of nephrologists who saw more than 20 AKI
      patients/year were significantly different in stopping dialysis with clinical
      stabilization of blood pressure (p < 0.001), improvement in respiratory
      parameters (p = 0.005), improvement in pre-dialysis blood urea nitrogen (BUN)
      levels despite the same dose of dialysis (p = 0.05) and resolution of oliguria (p
      = 0.025) compared to those who saw fewer cases. CONCLUSION: Resolution of
      oliguria was the commonest factor used to help deciding to stop dialysis in
      improving AKI. However, considerable variation was noted among US nephrologists
      who participated in this survey, regarding what criteria they used to withdraw
      dialysis in the setting of improving AKI. These results call for more studies in
      withdrawing dialysis in the setting of AKI that could lead to guideline
      formulation.

PMID- 25999064
TI  - Qualitative and quantitative image analysis of CT and MR imaging in patients with
      neuroendocrine liver metastases in comparison to (68)Ga-DOTATOC PET.
AB  - PURPOSE: To compare lesion conspicuity in patients with liver metastases arising
      from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using MRI, PET and
      CT. MATERIALS AND METHODS: 16 patients with GEP-NETs were evaluated using non
      contrast MRI, contrast-enhanced (CE) MRI using Gd-EOB-DTPA and CE-(68)Ga-DOTATOC
      PET. Quantitative analyses were performed by two blinded readers using ROI
      analyses quantifying contrast ratios (CR) between normal liver-tissue and GEP-NET
      metastases. Qualitative analyses were performed evaluating primary visibility and
      spatial detectability of all lesions. RESULTS: 103 of the same liver metastases
      were detected on all modalities. Qualitatively, lesion conspicuity was superior
      on CE-MRI imaging compared to non-contrast MR-sequences (T2, DWI, fl2D, fl3D), as
      well as arterial- and portal-venous phase CT. Concerning detectability of
      lesions, CE-MRI was superior to all other modalities. The quantitative ROI
      analysis demonstrated improved CR for DWI compared to all other non-contrast MR
      sequences (p<0.001). CE-MRI presented with higher CR-values compared to CE-(68)Ga
      DOTATOC PET/CT (p<0.001). CONCLUSIONS: Anatomic imaging using non contrast MRI
      with fl2D-and fl3D-sequences in combination with the molecular imaging modality
      (68)Ga-DOTATOC PET is optimal for the assessment of liver lesions in GEP-NET
      patients. Even though CE-MRI was superior to non-contrast MRI, non-contrast MRI
      is sufficient to detect and quantify liver metastases in daily routine,
      especially in combination with DW-Imaging.

PMID- 25999062
TI  - DNA replication origin activation in space and time.
AB  - DNA replication begins with the assembly of pre-replication complexes (pre-RCs)
      at thousands of DNA replication origins during the G1 phase of the cell cycle. At
      the G1-S-phase transition, pre-RCs are converted into pre-initiation complexes,
      in which the replicative helicase is activated, leading to DNA unwinding and
      initiation of DNA synthesis. However, only a subset of origins are activated
      during any S phase. Recent insights into the mechanisms underlying this choice
      reveal how flexibility in origin usage and temporal activation are linked to
      chromosome structure and organization, cell growth and differentiation, and
      replication stress. 

PMID- 25999066
TI  - Scenarios of large mammal loss in Europe for the 21st century.
AB  - Distributions and populations of large mammals are declining globally, leading to
      an increase in their extinction risk. We forecasted the distribution of extant
      European large mammals (17 carnivores and 10 ungulates) based on 2 Rio+20
      scenarios of socioeconomic development: business as usual and reduced impact
      through changes in human consumption of natural resources. These scenarios are
      linked to scenarios of land-use change and climate change through the spatial
      allocation of land conversion up to 2050. We used a hierarchical framework to
      forecast the extent and distribution of mammal habitat based on species' habitat
      preferences (as described in the International Union for Conservation of Nature
      Red List database) within a suitable climatic space fitted to the species'
      current geographic range. We analyzed the geographic and taxonomic variation of
      habitat loss for large mammals and the potential effect of the reduced impact
      policy on loss mitigation. Averaging across scenarios, European large mammals
      were predicted to lose 10% of their habitat by 2050 (25% in the worst-case
      scenario). Predicted loss was much higher for species in northwestern Europe,
      where habitat is expected to be lost due to climate and land-use change. Change
      in human consumption patterns was predicted to substantially improve the
      conservation of habitat for European large mammals, but not enough to reduce
      extinction risk if species cannot adapt locally to climate change or disperse. 

PMID- 25999067
TI  - Technology and the bedside nurse: an exploration and review of implications for
      practice.
AB  - Bedside technology pressures nurses to integrate and master a variety of new
      tools, devices, and methods of monitoring patient status. We review opportunities
      and challenges in the relationship between bedside nursing and technology. The
      increasing amount of available technology has impacted bedside nurses. The
      relationship between bedside nursing and technology is largely positive. Big data
      holds great potential for translating digital patient information into expanded
      knowledge tools for the bedside nurse, the development of which require nursing
      involvement. More research is needed to explore the concept of the nurse as
      advocate in high-technology patient care. 

PMID- 25999068
TI  - Blood pressure and the obese.
AB  - With the prevalence of obesity escalating globally, an increasing number of
      patients who are obese are seeking elective or requiring emergency surgery.
      Certified registered nurse anesthetists are challenged to provide vigilant, safe
      care. The ability to provide supportive therapy and make anesthetic adjustments
      is often hindered with obesity. Although technological advancements may enhance
      patient care delivery, health care providers must question why and how specific
      tasks are performed. Health care providers should challenge themselves to acquire
      and evaluate current evidence that enables communication with colleagues,
      dissemination of findings to health care providers worldwide, and implementation
      of evidence-based practice. 

PMID- 25999065
TI  - Hepatoprotective and anti-tumor effects of targeting MMP-9 in hepatocellular
      carcinoma and its relation to vascular invasion markers.
AB  - The current study aims to evaluate the hepatoprotective and antitumor efficacy of
      doxycycline, as an matrix metalloproteases-9 (MMP-9) inhibitor, in an in vivo
      model of hepatocellular carcinoma (HCC). HCC was induced experimentally by
      thiocetamide (200 mg/kg) in rats that were treated with doxycycline (5 mg/kg for
      16 weeks). Tumor severity was evaluated by measuring alpha-fetoprotein (AFP)
      levels, histopathologically by investigating liver sections stained with
      hematoxylin/eosin and assessing the survival rate. Liver homogenates were used
      for the measurements of MMP-9, fascin and hepatic heparan sulfate proteoglycan
      (HSPG) levels. Oxidative stress markers [malonaldehyde (MDA) and glutathione] as
      well as fibroblast growth factor-2 (FGF-2) gene expression were also among the
      assessed indicators. HCC in human and animal samples showed significant elevation
      in the levels of MMP-9 (231.7, 90 %), fascin (33.17, 140 %), as well as FGF-2
      gene expression (342 % in animal samples; all respectively), associated with a
      significant decrease in hepatic HSPG level. Treatment of rats with doxycycline
      increased the animal survival rate (90 %) and decreased serum AFP level.
      Moreover, doxycycline ameliorated fibrosis and the induced massive hepatic tissue
      breakdown. It also restored the integrity of hepatic HSPGs and showed a
      magnificent inhibitory effect of tumor invasion cascade by significantly reducing
      the activities of MMP-9 (42 %) and fascin (50 %), as well as reducing the gene
      expression of FGF-2 (85.7 %). Furthermore, the antioxidant impact of doxycycline
      was evidenced by the significant elevation in glutathione level and depressing
      MDA level. To this end, doxycycline, proved promising hepatoprotective and
      antitumor activity and opens, thereby, a new horizon against vascular migration
      ability of the tumor cells.

PMID- 25999069
TI  - Technology and monitoring patients at the bedside.
AB  - Hospital technology has aggressively improved over the past 50 years. With the
      primary intent of making health care more efficient and safer, the bedside nurse
      has been impacted by all of these changes. The growth and utilization of point-of
      care testing, automated dispensing systems, electronic medication records,
      electronic health records, mobile and digital radiography, and computerized
      provider order entry have continued to foster the growth of Nursing autonomy and
      the expectation of nurses' critical thinking. The usability and utility of these
      advancing technologies are key components to end-user satisfaction and ultimately
      the adoption of the technology by the bedside nurse.

PMID- 25999070
TI  - Transforming home health nursing with telehealth technology.
AB  - Telehealth technology is an evidence-based delivery model tool that can be
      integrated into the plan of care for mental health patients. Telehealth
      technology empowers access to health care, can help decrease or prevent hospital
      readmissions, assist home health nurses provide shared decision making, and
      focuses on collaborative care. Telehealth and the recovery model have transformed
      the role of the home health nurse. Nurses need to be proactive and respond to
      rapidly emerging technologies that are transforming their role in home care. 

PMID- 25999071
TI  - Potentials of internet-based patient engagement and education programs to reduce
      hospital readmissions: a spotlight on need in heart failure.
AB  - Internet-based applications and mobile health technology has advanced at
      unprecedented rates over the last decade and has proved to be a highly effective
      platform for communication. Simultaneously, the United States health care system
      has reached a critical and unsustainable level of spending, arising largely from
      ingrained system inefficiencies and overall suboptimum communication. Internet
      based and mobile health technology offers an innovative solution to both of these
      problems. The prevention of readmissions for heart failure provides an excellent
      example of how this new technology can be used in today's health care environment
      to improve patient care. 

PMID- 25999072
TI  - Nurse knowledge of intrahospital transport.
AB  - Preventable adverse events and other medical errors occur to hundreds of
      thousands of Americans every year. The financial burden of these preventable
      events is estimated to be $29 billion. According to the World Health
      Organization, reducing medical errors has become an international concern.
      Protecting patients from harm is a primary responsibility of all nurses
      regardless of whether the nurse works in the intensive care unit or operating
      room. Adherence to policies to maintain patient safety can be discerned once the
      level of knowledge of these policies among nurses is determined. 

PMID- 25999073
TI  - Medication order entry and clinical decision support: current nursing informatics
      issues.
AB  - The Health Information Technology for Economic and Clinical Health (HITECH) Act
      has greatly increased the acceptance of electronic health record technology by
      providing incentives and punishment standards. A key criterion of the HITECH Act,
      meaningful use, has vendors clamoring to design clinical decision support (CDS)
      systems that fulfill this objective. Users should be aware that more emphasis may
      be placed on achieving the goals for compliance than on working out details that
      are clinically meaningful. Nurses can play a crucial rule in collaboratively
      supporting CDS initiative changes that make patient care more effective and
      efficient.

PMID- 25999074
TI  - Utilization of clinical practice guidelines: barriers and facilitators.
AB  - Clinical practice guidelines augment clinician decision making. Researchers cite
      a lack of knowledge of guideline existence, complexity of guidelines, staff
      attitude, lack of training, time and resource constraints as reasons for
      nonadherence. This project sought to understand factors that promote or prevent
      guideline implementation at the point of care. Respondents' viewed clinical
      practice guidelines as valid tools necessary to standardize patient care and
      exhibited proficiency in synthesis and integration of guidelines into clinical
      decisions and treatment plans. Efficient and effective guidelines impact patient
      safety and quality by increasing the consistency of behavior and replacing
      idiosyncratic behaviors with best practices. 

PMID- 25999075
TI  - Simulation and rubrics: technology and grading student performance in nurse
      anesthesia education.
AB  - The use of simulation technology has introduced a challenge for simulation nurse
      educators: evaluation of student performance. The subjectivity of student
      performance evaluation has been in need of improvement. It is imperative to
      provide clear and consistent information to the learner of expectations for their
      performance. Educators use objectives to define for the learner what the primary
      focus will be in the learning activities. Creation of rubrics to replace
      checklists to evaluate learner performance is a team task. Improved rubrics
      assist instructors in providing valuable, immediate, and postactivity feedback
      and consistency among instructors, and improved inter-rater reliability. 

PMID- 25999076
TI  - Geriatric simulation: practicing management and leadership in care of the older
      adult.
AB  - According to the Centers for Disease Control and Prevention, patients age 65 and
      older account for 43% of hospital days. The complexity of caring for older adults
      affords nursing students opportunities to assess, prioritize, intervene,
      advocate, and experience being a member of an interdisciplinary health care team.
      However, these multifaceted hospital experiences are not consistently available
      for all students. Nursing clinical simulation (NCS) can augment or replace
      specific clinical hours and provide clinically relevant experiences to practice
      management and leadership skills while caring for older adults. This article
      describes a geriatric management and leadership NCS. 

PMID- 25999077
TI  - The influence of technology in nursing education.
AB  - The complexity of the relationship between nursing and technology is not new. The
      complexity has increased with the advent of new technology and technological
      devices. For faculty who are in the clinical area on a limited basis, and for
      nurses who are not involved in decisions related to the adoption of technology,
      terms and concepts related to technology can be misconstrued or misunderstood. An
      overview of some major terms used in reference to technology and technological
      approaches can only enhance the intricate relationship between nursing and
      technology. 

PMID- 25999078
TI  - Faculty development in simulation education.
AB  - Over the past 10 years, education in nursing has changed and simulation is a new
      teaching technology being used. Unfortunately, lack of training of how to use
      simulation in education can translate into poor educational pedagogy. This
      article introduces the importance of training educators and clinicians to use
      simulation technology according to defined standards and recommendations. A
      literature search revealed a dearth of research related to faculty training.
      Described are some programs in place across the United States that have been
      developed to facilitate education of faculty in use of simulation technology and
      methodology.

PMID- 25999079
TI  - Thinking of serving nursing abroad: how technology assists nurses on mission
      trips.
AB  - Advances in technology have assisted in the proliferation of short-term, faith
      based international medical mission trips. Many of these mission trips include
      health care not only to local citizens but also building schools and churches and
      sharing the Gospel of Jesus Christ. Included in this article are my own personal
      experiences in short-term, faith-based medical missions. A step-by-step guide is
      offered to help prepare inexperienced mission participants gain insight into
      short-term mission trips. Advanced planning, fundraising, collaboration, and
      being open to change are key elements to successful participation in these life
      changing missions. 

PMID- 25999080
TI  - Perioperative nurses' knowledge of indicators for pressure ulcer development in
      the surgical patient population.
AB  - Despite focused attention to improve the quality and safety of patient care, and
      the financial impact pressure ulcers (PUs) can have on a health care provider or
      institution, evidence supports that PUs continue to occur in other patient
      populations during admission to the hospital. An example of a patient population
      in which evidence indicates that the development of PUs occurs, is patients who
      have a surgical procedure. The article discusses a project designed to identify
      potential knowledge deficits among perioperative nurses of indicators for PU
      development in the surgical patient population. 

PMID- 25999081
TI  - Technology in nursing: the mandate for new implementation and adoption
      approaches.

PMID- 25999082
TI  - Transforming nursing practice with technology.

PMID- 25999085
TI  - Computational eco-systems biology in Tara Oceans: translating data into
      knowledge.

PMID- 25999086
TI  - The making of Tara Oceans: funding blue skies research for our Blue Planet.

PMID- 25999087
TI  - Diverse activity of human secretory phospholipases A2 on the migration of human
      vascular smooth muscle cells.
AB  - OBJECTIVE: Investigation of the diversity of human secretory phospholipases A2
      (sPLA2) on the migration of human vascular smooth muscle cells (VSMC). MATERIAL:
      We investigated the impact of sPLA2 IIA, V, and X and of oleic acid, linoleic
      acid and lysophosphatidylcholine on the migration of human VSMC. METHODS:
      Recombinant human sPLA2's and Boyden's chamber method were applied. RESULTS:
      sPLA2, IIA but not V or X enhanced migration of VSMC in a dose/time dependent
      manner. Oleic and linoleic acids, and lysophosphatidylcholine markedly enhanced
      migration. CONCLUSIONS: These results imply that sPLA2 IIA, which is known to be
      present in the arterial wall in the vicinity of VSMC, as well as products of
      lipid hydrolysis induced by sPLA2, enhance the migration of VSMC, and thus may
      contribute to atherogenic process.

PMID- 25999088
TI  - Keratitis caused by moulds in Santa Lucia Ophthalmology Hospital in Buenos Aires,
      Argentina.
AB  - BACKGROUND: Mycotic keratitis by moulds (MKM) is an important cause for corneal
      blindness and usually carries an unfavorable prognosis. AIMS: This study
      describes the risk factors and demographic and microbiological features of all
      MKM cases in Santa Lucia Ophthalmology Hospital during a period of 6 years.
      METHODS: A prospective study was performed for all MKM cases diagnosed between
      October 2007 and September 2013. RESULTS: Among 157 diagnosed cases, direct
      microscopic examination and culture were positive in 97 and 96% of the cases
      respectively. MKM represents 17% of all microbiologically confirmed corneal
      abscesses. No significant differences were detected in annual MKM frequencies
      across the study period, suggesting that MKM incidence remains constant over
      time. A male-to-female ratio was observed (2.8:1); the most affected age groups
      ranged from 31 to 40 years old (males) and 61-70 years old (females). The most
      frequent predisposing factor was trauma (40%) followed by the use of contact
      lenses (9%), herpetic abscesses (5%) and diabetes (4%). The predominant genera
      were Fusarium (66%), Aspergillus (10%), Curvularia (6%) and Alternaria (4%). The
      most frequent agent was Fusarium solani species complex (52%). More than two
      thirds of the cases were produced by only 3 species or complexes. However, at
      least 29 different species were detected in the remaining cases. This is the
      first report of Pholiota sp. as causative agent of human MKM. CONCLUSIONS:
      Argentina lacks extensive epidemiological and clinical data on MKM. This six-year
      study performed in Argentina is a first step leading to a better understanding of
      MKM epidemiology in our country.

PMID- 25999089
TI  - Signal enhancement in ultraflat electrochemical DNA biosensors.
AB  - The ability of holding back the undesired molecules, but at the same time to
      provide the right distribution and orientation of the bioreceptors, are critical
      targets to reach an efficient hybridization and enhanced detection in
      electrochemical DNA biosensors. The main actors responsible of these key
      functions are the substrate of the sensor and the interface auto-assembled on it.
      In this paper we present the annealing as a method to improve commercial gold
      evaporated substrates for biosensor applications. The restructuring of granulated
      gold surface by means of annealing heating treatment leads to the formation of
      ultraflat gold lamellar terraces. The formation of terraces was characterized
      with scanning tunneling microscopy and optical interferometry. The performance of
      the sensor sensitivity on granular substrates and ultraflat substrates was
      studied, concerning the orientation and surface coverage of the bioreceptor
      interface applied in electrochemical biosensor. The hybridization efficiency of
      ferrocene-labeled DNA amplified by PCR was characterized with surface plasmon
      resonance and electrochemistry. The experimental results demonstrate that
      annealing process, positive influence on optical and voltammetric readings, due
      to a structured organization of the bioreceptors on the flat substrate, gaining
      more efficient immobilization and DNA hybridization. The results suggest the
      annealing as a powerful tool for improving gold substrates in biosensors
      applications. 

PMID- 25999090
TI  - Treatment of heart failure with preserved ejection fraction. An unresolved
      problem.

PMID- 25999091
TI  - Flexible Ureteroscopy versus Retroperitoneal Laparoscopic Ureterolithotomy for
      the Treatment of Proximal Ureteral Stones >15 mm: A Single Surgeon Experience.
AB  - OBJECTIVE: To compare safety and effectiveness of flexible ureteroscopy (F-URS)
      and laparoscopic retroperitoneal ureterolithotomy (L-RU) in treatment of proximal
      ureteral stones larger than 15 mm. MATERIALS AND METHODS: This study included 103
      patients treated with L-RU (Group I), and 80 patients treated with F-URS (Group
      II) due to proximal ureteral stones larger than 1.5 cm, in a single center.
      Patients' characteristics and procedure-related parameters including success
      rate, operation time, hospital stay, postoperative visual analogue scale (VAS)
      scores, auxiliary procedures, and complications were compared between Groups I
      and II. RESULTS: It was seen that both methods were effective in the treatment of
      large ureteral stones; however, R-LU provided a higher stone-free rate (100 vs.
      87.5%), a lower complication rate (10.6 vs. 23.7%), and a shorter operation time
      (65.4 vs. 75.1 min). On the other hand, patients treated with F-URS had less
      postoperative pain, a shorter hospital stay, a faster return to daily activities.
      CONCLUSIONS: For treatment of large proximal ureteral stones, L-RU provides
      significantly higher success and lower retreatment rate compared with F-URS. Our
      results also indicate that R-LU, which has been regarded as an invasive procedure
      is not as invasive as it is thought to be, and it must be kept in mind that F-URS
      may cause complications despite its noninvasive nature.

PMID- 25999092
TI  - Molecular characterization of quinolone resistance mechanisms and extended
      spectrum beta-lactamase production in Escherichia coli isolated from dogs.
AB  - The increasing prevalence of antimicrobial resistances is now a worldwide
      problem. Investigating the mechanisms by which pets harboring resistant strains
      may receive and/or transfer resistance determinants is essential to better
      understanding how owners and pets can interact safely. Here, we characterized the
      genetic determinants conferring resistance to beta-lactams and quinolones in 38
      multidrug-resistant Escherichia coli isolated from fecal samples of dogs, through
      PCR and sequencing. The most frequent genotype included the beta-lactamase groups
      TEM (n=5), and both TEM+CTX-M-1 (n=5). Within the CTX-M group, we identified the
      genes CTX-M-32, CTX-M-1, CTX-M-15, CTX-M-55/79, CTX-M-14 and CTX-M-2/44. Thirty
      isolates resistant to ciprofloxacin presented two mutations in the gyrA gene and
      one or two mutations in the parC gene. A mutation in gyrA (reported here for the
      first time), due to a transversion and transition (TCG->GTG) originating a
      substitution of a serine by a valine in position 83 was also detected. The
      plasmid-encoded quinolone resistance gene, qnrs1, was detected in three isolates.
      Dogs can be a reservoir of genetic determinants conferring antimicrobial
      resistance and thus may play an important role in the spread of antimicrobial
      resistance to humans and other co-habitant animals. 

PMID- 25999093
TI  - Increased localization precision by interference fringe analysis.
AB  - We report a novel optical single-emitter-localization methodology that uses the
      phase induced by path length differences in a Mach-Zehnder interferometer to
      improve localization precision. Using information theory, we demonstrate that the
      localization capability of a modified Fourier domain signal generated by photon
      interference enables a more precise localization compared to a standard Gaussian
      intensity distribution of the corresponding point-spread function. The
      calculations were verified by numerical simulations and an exemplary experiment,
      where the centers of metal nanoparticles were localized to a precision of 3 nm. 

PMID- 25999094
TI  - Phylogenetic Characterization of a Novel Insect-Specific Flavivirus Detected in a
      Culex Pool, Collected from Assam, India.
AB  - OBJECTIVE: We report the phylogenetic characterization of a unique flavivirus
      sequence detected in a wild Culex tritaeniorhynchus mosquito pool, collected from
      the northeast Indian state of Assam. METHODS: DNA and RNA were extracted from
      field-collected mosquito pools. Extracts were subjected to PCR and reverse
      transcriptase PCR amplification using universal and type-specific primers for
      direct detection of flavivirus-specific viral nucleic acids. An amplified
      flavivirus nonstructural protein 5 (NS5) genetic region was sequenced and BLAST
      searched, and phylogenetic analyses performed with reference sequences retrieved
      from GenBank. RESULTS: Phylogenetic analyses revealed the sequence to be related
      to insect-specific flaviviruses (ISFs) of the genus Flavivirus, family
      Flaviviridae. Despite being related to the Palm Creek virus (PCV; an ISF very
      recently reported from Northern Australia), the present sequence (provisionally
      named Assam virus) was found to be highly divergent from PCV and other ISF
      sequences available in GenBank. The partial NS5 sequence analysis demonstrated
      low nucleotide sequence identity (66-77%) with known ISFs reported from other
      parts of the globe. CONCLUSION: Findings of this study suggest the presence of a
      candidate novel ISF - the first to be reported from India.

PMID- 25999095
TI  - Maternal age matters: for a lifetime, or longer.

PMID- 25999096
TI  - Association between maternal age at childbirth and child and adult outcomes in
      the offspring: a prospective study in five low-income and middle-income countries
      (COHORTS collaboration).
AB  - BACKGROUND: Both young and advanced maternal age is associated with adverse birth
      and child outcomes. Few studies have examined these associations in low-income
      and middle-income countries (LMICs) and none have studied adult outcomes in the
      offspring. We aimed to examine both child and adult outcomes in five LMICs.
      METHODS: In this prospective study, we pooled data from COHORTS (Consortium for
      Health Orientated Research in Transitioning Societies)-a collaboration of five
      birth cohorts from LMICs (Brazil, Guatemala, India, the Philippines, and South
      Africa), in which mothers were recruited before or during pregnancy, and the
      children followed up to adulthood. We examined associations between maternal age
      and offspring birthweight, gestational age at birth, height-for-age and weight
      for-height Z scores in childhood, attained schooling, and adult height, body
      composition (body-mass index, waist circumference, fat, and lean mass), and
      cardiometabolic risk factors (blood pressure and fasting plasma glucose
      concentration), along with binary variables derived from these. Analyses were
      unadjusted and adjusted for maternal socioeconomic status, height and parity, and
      breastfeeding duration. FINDINGS: We obtained data for 22 188 mothers from the
      five cohorts, enrolment into which took place at various times between 1969 and
      1989. Data for maternal age and at least one outcome were available for 19 403
      offspring (87%). In unadjusted analyses, younger (<=19 years) and older (>=35
      years) maternal age were associated with lower birthweight, gestational age,
      child nutritional status, and schooling. After adjustment, associations with
      younger maternal age remained for low birthweight (odds ratio [OR] 1.18 (95% CI
      1.02-1.36)], preterm birth (1.26 [1.03-1.53]), 2-year stunting (1.46 [1.25
      1.70]), and failure to complete secondary schooling (1.38 [1.18-1.62]) compared
      with mothers aged 20-24 years. After adjustment, older maternal age remained
      associated with increased risk of preterm birth (OR 1.33 [95% CI 1.05-1.67]), but
      children of older mothers had less 2-year stunting (0.64 [0.54-0.77]) and failure
      to complete secondary schooling (0.59 [0.48-0.71]) than did those with mothers
      aged 20-24 years. Offspring of both younger and older mothers had higher adult
      fasting glucose concentrations (roughly 0.05 mmol/L). INTERPRETATION: Children of
      young mothers in LMICs are disadvantaged at birth and in childhood nutrition and
      schooling. Efforts to prevent early childbearing should be strengthened. After
      adjustment for confounders, children of older mothers have advantages in
      nutritional status and schooling. Extremes of maternal age could be associated
      with disturbed offspring glucose metabolism. FUNDING: Wellcome Trust and the Bill
      & Melinda Gates Foundation.

PMID- 25999097
TI  - Clinical, Angiographic, Functional, and Imaging Outcomes 12 Months After
      Implantation of Drug-Eluting Bioresorbable Vascular Scaffolds in Acute Coronary
      Syndromes.
AB  - OBJECTIVES: The purpose of this study was to describe the multimodal outcome 12
      months after implantation of coronary bioresorbable scaffolds (BVS) for the
      treatment of patients with acute coronary syndromes (ACS). BACKGROUND: Functional
      and imaging data on the use of BVS are limited to simple, stable lesions; in the
      setting of ACS, only short-term clinical follow-up data are available, and no
      information from intracoronary imaging and vasomotion tests has been reported.
      METHODS: A total of 133 patients (age 62 +/- 12 years, 74% males, 15% diabetic)
      underwent BVS (n = 166) implantation for the treatment of thrombotic lesions in
      the setting of ACS (43% non-ST-segment elevation myocardial infarction, 38% ST
      segment elevation myocardial infarction, 20% unstable angina). Clinical,
      angiographic, intracoronary imaging, and vasomotor endpoints were evaluated at 12
      months. RESULTS: During the 374 days (interquartile range: 359 to 411 days) of
      follow-up, there were 4 deaths; 3 definite and 1 probable in-BVS thromboses (all
      in the first 6 months). At 12-month angiography (75 patients, 83 BVS), in-segment
      late lumen loss was 0.19 +/- 0.45 mm, and 3 (4%) patients showed binary
      restenosis. Optical coherence tomography (80 BVS, n = 70) showed a mean lumen
      area of 6.3 +/- 2.3 mm(2). Malapposition was evidenced in 21 (26%) BVS.
      Endothelium-dependent and -independent vasodilation were observed in 48% and 49%
      of the BVS. CONCLUSIONS: Twelve months after BVS implantation, clinical,
      intracoronary imaging, and vasomotion data appear to provide a rationale for the
      use of BVS in the setting of ACS and the basis for a randomized study.

PMID- 25999098
TI  - Biochemical Validation of Patient-Reported Symptom Onset Time in Patients With ST
      Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary
      Intervention.
AB  - OBJECTIVES: This study evaluated a biochemical validation of patient-reported
      symptom onset time in patients with ST-segment elevation myocardial infarction
      (STEMI). BACKGROUND: Symptom onset time is an important metric but has never been
      formally validated. METHODS: The Mayo Clinic Percutaneous Coronary Intervention
      (PCI) Registry was interrogated to obtain baseline, procedural, and outcome data
      on 607 STEMI patients undergoing primary PCI. Biochemical onset time was
      determined by backward extrapolation of serial increasing cardiac troponin T
      (cTnT) measurements. RESULTS: The median patient-reported onset time was 12 min
      later than the calculated time of first cTnT increase and was therefore estimated
      to be 4.2 h later than the biochemical onset time (interquartile range: 1.9 to
      11.1 h; p < 0.001), assuming a 4-h interval between coronary occlusion and first
      cTnT increase. Conventional ischemic time showed no association with infarct size
      (correlation with peak cTnT: r = 0.023; p = 0.61) or 1-year mortality (hazard
      ratio: 0.97 per doubling; 95% confidence interval: 0.68 to 1.40; p = 0.88).
      However, after recalculation of ischemic time with biochemical onset time,
      significant associations with infarct size (r = 0.14; p = 0.001) and 1-year
      mortality (hazard ratio: 1.70 per doubling; 95% confidence interval: 1.20 to
      2.40; p = 0.003) were found. When underestimation of ischemic time by patient
      reported onset time increased, so did the risk of mortality. CONCLUSIONS:
      Although our point estimate should be interpreted with caution, our study
      indicates that the actual onset of STEMI is likely to be earlier than the patient
      reported onset time. Recalculation of ischemic time with biochemical onset time
      greatly enhanced its prognostic value. Underestimation of ischemic time by
      patient-reported onset time occurred more often in high-risk patients.

PMID- 25999099
TI  - A New Time Clock for ST-Segment Elevation Myocardial Infarction.

PMID- 25999101
TI  - Improving outcomes in older women?

PMID- 25999100
TI  - Sex-Related Outcomes in Elderly Patients Presenting With Non-ST-Segment Elevation
      Acute Coronary Syndrome: Insights From the Italian Elderly ACS Study.
AB  - OBJECTIVES: This study sought to investigate sex-related differences in treatment
      and outcomes in elderly patients with non-ST-segment elevation acute coronary
      syndromes (NSTEACS). BACKGROUND: Female sex and older age are usually associated
      with worse outcome in NSTEACS. The Italian Elderly ACS study enrolled NSTEACS
      patients aged 75 years of age and older in a randomized trial comparing an early
      aggressive with an initially conservative strategy and in a registry of patients
      with >=1 exclusion criteria of the trial. METHODS: We compared sexes in the
      pooled populations of the trial and registry. RESULTS: A total of 645 patients
      (313 from the trial and 332 from the registry), including 301 women (47%), were
      enrolled. Women were slightly older than men (82.1 +/- 5.0 years vs. 81.2 +/- 4.5
      years; p = 0.02), had lower hemoglobin levels (12.5 +/- 1.6 g/dl vs. 13.3 +/- 1.9
      g/dl; p < 0.001), and underwent fewer coronary revascularizations during the
      index admission (37.2% vs. 45.0%; p = 0.04). In-hospital adverse event rates were
      similar in both sexes; severe bleeding was uncommon (0.3% vs. 0%). The 1-year
      primary endpoint (composite of death, nonfatal myocardial infarction, disabling
      stroke, cardiac rehospitalization, and severe bleeding) occurred less often in
      women (27.6% vs. 38.7%; p < 0.01). Women not undergoing revascularization showed
      a 3-fold higher mortality, both in-hospital (8.5% vs. 2.7%; p = 0.05) and at 1
      year (21.6% vs. 8.1%; p = 0.002). CONCLUSIONS: Elderly women had a similar in
      hospital outcome and better 1-year outcome compared with men. Coronary
      revascularization in women was associated with lower 1-year mortality, without an
      increase in severe bleeding. Elderly women with NSTEACS should always be
      considered for early revascularization.

PMID- 25999103
TI  - Blood glucose variability: a new metric for interventional cardiology?

PMID- 25999102
TI  - Effect of daily glucose fluctuation on coronary plaque vulnerability in patients
      pre-treated with lipid-lowering therapy: a prospective observational study.
AB  - OBJECTIVES: This study sought to investigate the effect of daily glucose
      fluctuation on coronary plaque properties in patients with coronary artery
      disease (CAD) pre-treated with lipid-lowering therapy. BACKGROUND: There is
      growing evidence that glucose fluctuation, as a residual risk apart from
      dyslipidemia, is an important factor contributing to the development of CAD.
      METHODS: This prospective study enrolled 70 consecutive CAD patients who were
      referred for percutaneous coronary intervention and whose low-density lipoprotein
      cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without
      statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude
      of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit
      lesions were assessed by virtual histology intravascular ultrasound, and the
      volume percentage of necrotic core within the plaque (%NC) and the presence of
      thin-cap fibroatheroma were evaluated. RESULTS: In total, 165 lesions were
      evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well
      correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed
      that MAGE had the strongest effect on %NC (coefficient beta = 0.080 +/- 0.020
      [standard error], p < 0.001). The generalized linear mixed effect model revealed
      that MAGE was the only independent predictor of the presence of thin-cap
      fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p =
      0.007). CONCLUSIONS: Daily glucose fluctuation may have an effect on coronary
      plaque vulnerability in patients with CAD pre-treated with lipid-lowering
      therapy. Further investigations should address the rationale for the early
      detection and control of glucose fluctuation in the era of universal statin use
      for CAD patients.

PMID- 25999104
TI  - In-Stent Yellow Plaque at 1 Year After Implantation Is Associated With Future
      Event of Very Late Stent Failure: The DESNOTE Study (Detect the Event of Very
      late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima
      Determined by Angioscopy).
AB  - OBJECTIVES: This study examined whether coronary angioscopy-verified in-stent
      yellow plaque at 1 year after drug-eluting stent (DES) implantation is associated
      with future event of very late stent failure (VLSF). BACKGROUND: Atherosclerosis
      detected as yellow plaque by angioscopy has been associated with future events of
      acute coronary syndrome. Development of in-stent neoatherosclerosis is a probable
      mechanism of VLSF. METHODS: This study included 360 consecutive patients who
      received successful angioscopic examination at 1 year after implantation of a
      DES. They were clinically followed up for VLSF defined as cardiac death, acute
      myocardial infarction or unstable angina, or need for revascularization
      associated with the stent site. RESULTS: The follow-up interval was 1,558 +/- 890
      days (4.3 +/- 2.4 years). The incidence of VLSF was significantly higher in the
      patients with yellow plaque than in those without (8.1% vs. 1.6%; log rank p =
      0.02). Multivariable analysis revealed the presence of yellow plaque (hazard
      ratio [HR]: 5.38; p = 0.02) and absence of statin therapy (HR: 3.25; p = 0.02) as
      risks of VLSF. CONCLUSIONS: In-stent atherosclerosis evaluated by yellow plaque
      at 1 year after the implantation of DES and the absence of statin therapy were
      risks of VLSF. The underlying mechanism of VLSF appeared to be the progression of
      atherosclerosis as demonstrated by the yellow plaque.

PMID- 25999105
TI  - Neoatherosclerosis: detection and clinical consequences.

PMID- 25999107
TI  - Diagnostic Accuracy of Baseline Distal-to-Aortic Pressure Ratio to Assess
      Coronary Stenosis Severity: A Post-Hoc Analysis of the ADVISE II Study.

PMID- 25999106
TI  - Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free
      Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International,
      Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).
AB  - OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of
      the instantaneous wave-free ratio (iFR) to characterize, outside of a pre
      specified range of values, stenosis severity, as defined by fractional flow
      reserve (FFR) <=0.80, in a prospective, independent, controlled, core laboratory
      based environment. BACKGROUND: Studies with methodological heterogeneity have
      reported some discrepancies in the classification agreement between iFR and FFR.
      The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study
      was designed to overcome limitations of previous iFR versus FFR comparisons.
      METHODS: A total of 919 intermediate coronary stenoses were investigated during
      baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients)
      met core laboratory physiology criteria and are included in this report. RESULTS:
      The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly
      classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of
      87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p <
      0.001]). The proportion of stenoses properly classified by iFR outside of the pre
      specified treatment (<=0.85) and deferral (>=0.94) values was 91.6% (95% CI:
      88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of
      stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was
      94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators
      from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to
      72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis
      rigorous methodology, the diagnostic value of iFR in establishing the functional
      significance of coronary stenoses, and highlights its complementariness with FFR
      when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent
      Stenosis Evaluation II-ADVISE II; NCT01740895).

PMID- 25999109
TI  - Twofers and transaortic valve replacements.

PMID- 25999108
TI  - Optimal Implantation Depth and Adherence to Guidelines on Permanent Pacing to
      Improve the Results of Transcatheter Aortic Valve Replacement With the Medtronic
      CoreValve System: The CoreValve Prospective, International, Post-Market ADVANCE
      II Study.
AB  - OBJECTIVES: The aim of the CoreValve prospective, international, post-market
      ADVANCE-II study was to define the rates of conduction disturbances and permanent
      pacemaker implantation (PPI) after transcatheter aortic valve replacement with
      the Medtronic CoreValve System (Minneapolis, Minnesota) using optimized
      implantation techniques and application of international guidelines on cardiac
      pacing. BACKGROUND: Conduction disturbances are a frequent complication of
      transcatheter aortic valve replacement. The rates of PPI in the published reports
      vary according to bioprosthesis type and the indications for PPI. METHODS: The
      primary endpoint was the 30-day incidence of PPI with Class I/II indications when
      the Medtronic CoreValve System was implanted at an optimal depth (<=6 mm below
      the aortic annulus). The timing and resolution of all new-onset conduction
      disturbances were analyzed. RESULTS: A total of 194 patients were treated. The
      overall rate of PPI for Class I/II indications was 18.2%. An optimal depth was
      reached in 43.2% of patients, with a nonsignificantly lower incidence of PPI in
      patients with depths <=6 mm, compared with those with deeper implants (13.3% vs.
      21.1%; p = 0.14). In a paired analysis, new-onset left bundle branch block and
      first-degree atrioventricular block occurred in 45.4% and 39.0% of patients,
      respectively, and resolved spontaneously within 30 days in 43.2% and 73.9%,
      respectively. In patients with new PPI, the rate of intrinsic sinus rhythm
      increased from 25.9% at 7 days to 59.3% at 30 days (p = 0.004). CONCLUSIONS:
      Optimal Medtronic CoreValve System deployment and adherence to international
      guidelines on cardiac pacing are associated with a lower rate of new PPI after
      transcatheter aortic valve replacement, compared with results reported in
      previous studies. (CoreValve Advance-II Study: Prospective International Post
      Market Study [ADVANCE II]; NCT01624870).

PMID- 25999110
TI  - Percutaneous mitral valve replacement using a transvenous, transseptal approach:
      transvenous mitral valve replacement.
AB  - OBJECTIVES: The aim of this paper is to describe the feasibility of a novel
      transcatheter approach for mitral valve replacement using only venous access.
      BACKGROUND: Failure of mitral valve prostheses necessitating reoperation can
      represent a high-risk clinical scenario. Although repeat cardiac surgery remains
      the standard of care for most failed mitral valve operations, nascent
      transcatheter options are under development for patients at high or extremely
      risk of surgery. Most often, this is performed via a transapical approach in the
      operating room, with associated risk of complications as well as extended length
      of hospital stay. METHODS: We describe a case series of 4 consecutive patients at
      high risk of reoperation with degenerative mitral prostheses (bioprosthetic
      valves or rings) who successfully underwent transvenous, transseptal mitral valve
      replacement with a commercially available transcatheter heart valve. RESULTS:
      From April to May 2014, 4 consecutive patients underwent transvenous, transseptal
      mitral valve replacement with a transcatheter heart valve. The mean age was 72 +/
      9.9 years, and the average Society of Thoracic Surgeons risk score was 12.5 +/-
      7.2%. All patients had severe, life-limiting dyspnea. The 4 procedures were
      successful without intra- or post-procedural complications; echocardiography
      indicated a well-seated and functioning mitral valve-in-valve or valve-in-ring.
      Patients were discharged within 2 days after valve replacement with marked
      improvement in dyspnea. CONCLUSIONS: We describe an innovative technique of
      transcatheter mitral valve replacement. This case series demonstrates the
      feasibility of transcatheter mitral valve replacement using only femoral venous
      access, with a marked reduction in complications and length of hospital stay
      compared with transapical access or redo surgery.

PMID- 25999111
TI  - Hospital variation in carotid stenting outcomes.
AB  - OBJECTIVES: The aim of this study was to examine variation in outcomes for
      patients receiving carotid artery stenting (CAS) across a sample of U.S.
      hospitals and assess the extent to which this variation was attributable to
      differences in case mix and procedural volume. BACKGROUND: As CAS is increasingly
      being used throughout the United States, assessing hospital variation in CAS
      outcomes is critical to understanding and improving the quality of care for
      patients with carotid artery disease. METHODS: Hospitals participating in the
      National Cardiovascular Data Registry-Carotid Artery Endarterectomy and
      Revascularization Registry contributing more than 5 CAS procedures from 2005
      through 2013 were eligible for inclusion. We estimated unadjusted and risk
      standardized rates of in-hospital stroke or death for each participating hospital
      using a previously validated prediction model and applying hospital-level random
      effects. RESULTS: There were 188 hospitals contributing 19,381 CAS procedures
      during the period of interest. Unadjusted and risk-standardized in-hospital
      stroke or death rates ranged from 0% to 18.8% and 1.2% to 4.7%, respectively.
      Operator and hospital volumes were not significant predictors of outcomes after
      adjustment for case mix (p = 0.15 and p = 0.09, respectively). CONCLUSIONS: CAS
      outcomes vary 4-fold among hospitals, even after adjustment for differences in
      case mix. Future work is needed to identify the sources of this variation and
      develop initiatives to improve patient outcomes.

PMID- 25999112
TI  - Reply: plaque rupture in stable coronary artery disease.

PMID- 25999113
TI  - Plaque rupture in stable coronary artery disease.

PMID- 25999114
TI  - Left Atrial Decompression Using Unidirectional Left-to-Right Interatrial Shunt:
      Initial Experience in Treating Symptomatic Heart Failure With Preserved Ejection
      Fraction With the W-Wave Device.

PMID- 25999115
TI  - Should all stent patients have prolonged dual antiplatelet therapy?

PMID- 25999116
TI  - First-in-Human Implantation of a Direct Flow Medical Valve in a Radiolucent
      Mitral Annuloplasty Ring.

PMID- 25999117
TI  - Cyphering the mechanism of late failure of bioresorbable vascular scaffolds in
      percutaneous coronary intervention of the left main coronary artery.

PMID- 25999118
TI  - Sinus of Valsalva aneurysm causing extrinsic compression of the left main
      coronary artery.

PMID- 25999119
TI  - Erratum to: The activity of the artemisinic aldehyde Delta11(13) reductase
      promoter is important for artemisinin yield in different chemotypes of Artemisia
      annua L.

PMID- 25999121
TI  - Emotion recognition in temporal lobe epilepsy: A systematic review.
AB  - There is increasing interest in the understanding of emotion recognition deficits
      in temporal lobe epilepsy (TLE), the most common form of focal epilepsies. There
      are conflicting reports about impairments for different emotions in right and
      left temporal lobe epilepsy patients. A systematic review and a narrative
      synthesis was conducted for studies investigating emotion recognition (ER) in
      TLE. Embase, MEDLINE, PsychINFO and Pubmed were searched from 1990 to March 2015
      and reference lists were reviewed. 996 citations were identified and 43 studies
      were finally included. ER deficits are consistently observed across studies. A
      fear recognition deficit is always reported, followed by deficits in sadness and
      disgust recognition. Deficits are observed across visual and auditory domains.
      Conflicting evidence is present concerning the severity of ER deficits in right
      and left TLE. Studies on anterior temporal lobectomy report data similar to that
      observed in pre-surgical patients. Current evidence supports the conclusion that
      recognition of negative emotions is commonly impaired in TLE, particularly for
      fear, and in the visual domain. Future work should focus on more ecologically
      valid test, on longitudinal studies to assess the role of anterior temporal
      lobectomy, and to correlate ER measures to social functioning in everyday life. 

PMID- 25999122
TI  - Drug-induced hemichorea.

PMID- 25999123
TI  - Outcome of Patients Discharged From a Heart Failure Disease Management Program
      following Their Clinical and Echocardiographic Recovery.
AB  - OBJECTIVES: Heart failure (HF) is associated with high mortality and frequent
      hospitalizations. Disease management programs (DMPs) have a favorable impact on
      patients with HF. No data exist regarding the outcomes of patients discharged
      from such a program. METHODS: We examined the outcome of patients with severe
      systolic HF who were discharged from a DMP following full clinical and
      echocardiographic recovery. Data were reviewed for mortality, emergency room
      visits, hospitalizations, medication adherence and left ventricular ejection
      fraction (EF). RESULTS: At enrollment and discharge, the mean EF was 19 and 53%,
      respectively. At follow-up 46.2 months after discharge, 56% of patients had been
      to the emergency room, 34% were hospitalized a total of 41 times and 20% had
      died. In the patients who required hospitalization for HF, the mean EF upon
      rehospitalization had dropped to 23.4%. CONCLUSIONS: Many patients with initially
      severe systolic HF who had an almost full recovery in a multidisciplinary DMP had
      very poor outcomes once they were discharged from the program. It may be
      appropriate to revisit the practice of discharging patients from DMPs once they
      have reached a specific clinical target.

PMID- 25999124
TI  - A virtual environment for medical radiation collaborative learning.
AB  - A software-based environment was developed to provide practical training in
      medical radiation principles and safety. The Virtual Radiation Laboratory
      application allowed students to conduct virtual experiments using simulated
      diagnostic and radiotherapy X-ray generators. The experiments were designed to
      teach students about the inverse square law, half value layer and radiation
      protection measures and utilised genuine clinical and experimental data.
      Evaluation of the application was conducted in order to ascertain the impact of
      the software on students' understanding, satisfaction and collaborative learning
      skills and also to determine potential further improvements to the software and
      guidelines for its continued use. Feedback was gathered via an anonymous online
      survey consisting of a mixture of Likert-style questions and short answer open
      questions. Student feedback was highly positive with 80 % of students reporting
      increased understanding of radiation protection principles. Furthermore 72 %
      enjoyed using the software and 87 % of students felt that the project facilitated
      collaboration within small groups. The main themes arising in the qualitative
      feedback comments related to efficiency and effectiveness of teaching, safety of
      environment, collaboration and realism. Staff and students both report gains in
      efficiency and effectiveness associated with the virtual experiments. In addition
      students particularly value the visualisation of "invisible" physical principles
      and increased opportunity for experimentation and collaborative problem-based
      learning. Similar ventures will benefit from adopting an approach that allows for
      individual experimentation while visualizing challenging concepts. 

PMID- 25999125
TI  - Fluoroscopic motion study confirming the stability of a medial pivot design total
      knee arthroplasty.
AB  - BACKGROUND: The ideal total knee arthroplasty should provide maximum range of
      motion and functional stability for all desired daily activities. The SAIPHTM
      (MatOrtho; UK) knee has a medial pivot knee kinematic pattern designed to achieve
      medial stability and an asymmetric posterior translation of the lateral femoral
      condyle during knee flexion and in this way attempts to mimic the natural knee
      motion. This study aims to analyze knee kinematics of the SAIPHTM total knee
      arthroplasty (TKA) by videofluoroscopy during four different weightbearing
      activities. METHODS: Fourteen consecutive patients operated on by a single
      surgeon, with a minimum follow-up of 24 months were included in this IRB-approved
      study. There were no exclusions based on patient's functional level. A medially
      conforming knee was implanted in all cases. Participants in the study were asked
      to perform the clinically relevant functional activities of pivoting, kneeling,
      lungeing and step-up/down activities while their knee motion was recorded by
      videofluoroscopy. RESULTS: Maximum knee flexion during the kneeling activity mean
      127 degrees  (100 degrees -155 degrees ). An asymmetric posterior translation of
      the lateral femoral condyle (LFC) was observed during pivoting, kneeling,
      lungeing and stepping. No paradoxical anterior translation of the femoral
      condyles was observed in any activity. CONCLUSION: The kinematics observed in
      this implant are similar in pattern, although smaller in magnitude, to normal
      functional knees, showing a posterior translation of the lateral femoral condyle
      during knee flexion, with internal rotation of the tibia, and no paradoxical
      anterior motion in any of the four weight bearing activities.

PMID- 25999120
TI  - Psychiatric disorders and leukocyte telomere length: Underlying mechanisms
      linking mental illness with cellular aging.
AB  - Many psychiatric illnesses are associated with early mortality and with an
      increased risk of developing physical diseases that are more typically seen in
      the elderly. Moreover, certain psychiatric illnesses may be associated with
      accelerated cellular aging, evidenced by shortened leukocyte telomere length
      (LTL), which could underlie this association. Shortened LTL reflects a cell's
      mitotic history and cumulative exposure to inflammation and oxidation as well as
      the availability of telomerase, a telomere-lengthening enzyme. Critically short
      telomeres can cause cells to undergo senescence, apoptosis or genomic
      instability, and shorter LTL correlates with poorer health and predicts
      mortality. Emerging data suggest that LTL may be reduced in certain psychiatric
      illnesses, perhaps in proportion to exposure to the psychiatric illnesses,
      although conflicting data exist. Telomerase has been less well characterized in
      psychiatric illnesses, but a role in depression and in antidepressant and
      neurotrophic effects has been suggested by preclinical and clinical studies. In
      this article, studies on LTL and telomerase activity in psychiatric illnesses are
      critically reviewed, potential mediators are discussed, and future directions are
      suggested. A deeper understanding of cellular aging in psychiatric illnesses
      could lead to re-conceptualizing them as systemic illnesses with manifestations
      inside and outside the brain and could identify new treatment targets. 

PMID- 25999126
TI  - Does adjustable-loop femoral cortical suspension loosen after anterior cruciate
      ligament reconstruction? A retrospective comparative study.
AB  - BACKGROUND: Recent biomechanical research has suggested that adjustable-loop
      graft suspension constructs in anterior cruciate ligament (ACL) reconstruction
      may loosen after deployment. Our objective was to compare short-term knee
      stability and graft failure rate between adjustable-loop and fixed-loop femoral
      cortical suspension in patients undergoing primary ACL reconstruction. METHODS: A
      consecutive series of 188 patients who underwent primary ACL reconstruction using
      hamstrings autograft by a single surgeon were divided into two groups; 73
      received adjustable-loop (TightRope RT (Arthrex Inc., Naples, FL)) and 115
      received fixed-loop (RetroButton (Arthrex Inc., Naples, FL)) femoral cortical
      suspension. The two groups were compared at six months, one year, and two years
      postoperatively using KT-1000 arthrometer testing and graft failure rate
      (revision surgery, grade 2+ Lachman test, any pivot shift, >5mm side-to-side KT
      1000 difference). RESULTS: There was no significant difference between the two
      groups in maximum side-to-side difference in KT-1000 testing at six months (mean
      1.51mm (adjustable-loop group) vs. 1.79mm (fixed-loop group), p=0.23), one year
      (mean 1.44mm vs. 1.64mm, p=0.48), or two years (mean 1.14mm vs. 1.07mm, p=0.90)
      postoperatively. There was no significant difference between the two groups in
      rate of graft failure (10% vs. 11%, p=0.71) or timing of graft failure in
      affected patients (mean 11.4months vs. 13.8months, p=0.51). CONCLUSIONS: We found
      no significant difference in postoperative knee stability or graft failure rate
      between adjustable-loop and fixed-loop femoral cortical suspension in patients
      undergoing primary ACL reconstruction. Our results suggest that adjustable-loop
      suspension does not clinically loosen after ACL reconstruction. LEVEL OF
      EVIDENCE: III (retrospective cohort study).

PMID- 25999127
TI  - Bevacizumab-Based Therapy for Patients with Brain Metastases from Non-Small-Cell
      Lung Cancer: Preliminary Results.
AB  - BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody that
      obstructs the vascular endothelial growth factor (VEGF) pathway. Despite its
      extensive employment in the treatment of primary tumors of the brain, experience
      of brain metastatic disease, a frequent complication in patients with lung
      cancer, is very limited. On the basis of the strong antiedemigenous effect and no
      risk of intracranial bleeding, we administered a bevacizumab-based chemotherapy
      to patients with non-small-cell lung cancer (NSCLC) and symptomatic metastatic
      brain lesions who were not suitable candidates for a specific local therapy.
      METHODS: The patients received bevacizumab 7.5 mg/kg and cisplatin 75 mg/m(2) on
      day 1, and gemcitabine 1,250 mg/m(2) on days 1 and 8, every 21 days. RESULTS: We
      studied 13 patients with clinical and radiological progressive brain metastases;
      the majority had a treatment-naive disease. Bevacizumab-based chemotherapy was
      found to be well tolerated and effective: progression-free survival (PFS) was 9.1
      months (range: 0.9-39.2+) and overall survival (OS) was 9.6 months (range 3
      41.5+). CONCLUSIONS: Bevacizumab-based therapy proved to be feasible and safe.
      The PFS and the OS data are very encouraging as well as the symptomatic benefit
      due to bevacizumab's high capacity to provide a long-lasting decrease of
      perilesional edema.

PMID- 25999128
TI  - Regioselective Acetylation of C21 Hydroxysteroids by the Bacterial
      Chloramphenicol Acetyltransferase I.
AB  - Chloramphenicol acetyltransferase I (CATI) detoxifies the antibiotic
      chloramphenicol and confers a corresponding resistance to bacteria. In this study
      we identified this enzyme as a steroid acetyltransferase and designed a new and
      efficient Escherichia-coli-based biocatalyst for the regioselective acetylation
      of C21 hydroxy groups in steroids of pharmaceutical interest. The cells carried a
      recombinant catI gene controlled by a constitutive promoter. The capacity of the
      whole-cell system to modify different hydroxysteroids was investigated, and NMR
      spectroscopy revealed that all substrates were selectively transformed into the
      corresponding 21-acetoxy derivatives. The biotransformation was optimized, and
      the reaction mechanism is discussed on the basis of a computationally modeled
      substrate docking into the crystal structure of CATI. 

PMID- 25999129
TI  - Population structure of Legionella spp. from environmental samples in Gabon,
      2013.
AB  - Aquatic environments are the most important source for Legionella spp. infections
      such as Legionnaires' disease and Pontiac fever. The reservoirs of Legionella
      spp. are mostly unclear in sub-Saharan Africa. The aim of this study, conducted
      in 2013, was to identify geographical areas of an increased risk for exposure to
      Legionella spp., and to describe the population structure of Legionella spp. from
      different water sources in a cross-sectional study in Gabon. Fresh water samples
      (n = 200) were cultured on Legionella selective agar; species were confirmed by
      MALDI-TOF, a Legionella pneumophila specific real-time PCR and 16S RNA gene
      sequencing. Serogroups were identified by agglutination test. The population
      structure was assessed by multilocus sequence typing (MLST). Legionella spp.
      isolates (n = 29) were frequently found in the hospital setting particularly in
      hot water systems. Open water bodies (i.e. rivers, lakes) were not contaminated
      with Legionella spp. Isolated L. pneumophila mainly belonged to serogroups 2-14
      (n = 19) and MLST sequence type ST1, ST75 (and related STs) and ST1911. In
      conclusion, hospitalized patients might have an increased risk to become infected
      with Legionella spp. in the studied areas in Gabon, particularly if they have
      risk factors such as comorbidities. Both broadly extended (ST1, ST75) and local
      lineages (ST1911) were present in our setting.

PMID- 25999130
TI  - Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog
      signaling pathway in breast cancer.
AB  - Metformin, a widely prescribed antidiabetic drug, has previously been shown to
      lower the risk of certain types of cancer, including that of breast cancer, and
      to improve prognosis. Its anticancer effects, which are mediated by the
      activation of AMP-activated protein kinase (AMPK), have become notable. The Sonic
      hedgehog (Shh) signaling pathway is involved in changes in mammary ducts and
      malignant transformation. The aim of the present study was to elucidate the role
      of the Shh pathway in mediating the anticancer effects of metformin and the
      correlation between AMPK and the Shh pathway. We investigated the effectiveness
      of metformin in inhibiting the proliferation, migration, invasion and stemness of
      breast cancer cells in vitro using RNA extraction and reverse transcription
      polymerase chain reaction (RT-PCR), western blot analysis, cell proliferation
      assay, scratch-wound assay (cell migration assay), cell invasion assay,
      mammosphere culture and flow cytometry. In in vivo experiments, a tumor xenograft
      model was used to detect the effects of metformin on cancer cell proliferation.
      The results revealed that the treatment of breast cancer cells with metformin led
      to the inhibition of the Shh signaling pathway. Importantly, metformin inhibited
      recombinant human Shh (rhShh)-induced cell migration, invasion, and stemness, and
      impaired cell proliferation both in vitro and in vivo. Furthermore, the small
      interfering RNA (siRNA)-mediated downregulation of AMPK reversed the inhibitory
      effects of metformin on rhShh-induced Gli-1 expression and stemness. Our findings
      identified a role of the Shh signaling pathway in the anticancer effects of
      metformin in breast cancer. Furthermore, we revealed that the metformin-mediated
      inhibition of the Shh signaling pathway may be dependent on AMPK.

PMID- 25999131
TI  - Awareness of folic acid use increases its consumption, and reduces the risk of
      spina bifida.
AB  - The majority of neural tube defects were believed to be folic acid (FA)
      preventable in the 1990s. The Japanese government recommended women planning
      pregnancy to take FA supplements of 400 MUg/d in 2000, but the incidence of spina
      bifida has not decreased. We aimed to evaluate the OR of having an infant with
      spina bifida for women who periconceptionally took FA supplements and the
      association between an increase in supplement use and possible promoters for the
      increase. This is a case-control study which used 360 case women who gave birth
      to newborns afflicted with spina bifida, and 2333 control women who gave birth to
      healthy newborns during the first 12 years of this century. They were divided
      into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic
      regression analyses were conducted to compute OR between cases and controls. The
      adjusted OR of having an infant with spina bifida for supplement users was 0.48
      in the first period, and 0.53 in the second period. The proportion of women who
      periconceptionally consumed supplements significantly increased from 10 % in the
      first period to 30 % in the second period. Awareness of the preventive role of FA
      was a promoter for an increase in supplement use, and thus an FA campaign in high
      school seems rational and effective. The failure of the current public health
      policy is responsible for an epidemic of spina bifida. Mandatory food
      fortification with FA is urgent and long overdue in Japan.

PMID- 25999132
TI  - Reduced reaction volumes and increased Taq DNA polymerase concentration improve
      STR profiling outcomes from a real-world low template DNA source: telogen hairs.
AB  - PURPOSE: The primary method for analysis of low template DNA (LTDNA) is known as
      the low copy number (LCN) method involving an increased number of PCR cycles
      (typically 34). In common with other LTDNA methods, LCN profiles are
      characterized by allelic imbalance, drop in, and drop out that require
      complicated interpretation rules. They often require replicate PCR reactions to
      generate a "consensus" profile in a specialized facility. An ideal method for
      analysis of LTDNA should enhance profiling outcomes without elevated error rates
      and be performed using standard facilities, with minimum additional cost.
      METHODS: In this study, we present a comparison of four method variations for the
      amplification of STRs from LTDNA with a widely used, commercially available kit
      (AmpFlSTR((r)) Profiler Plus((r))): the standard method, the standard method with
      a post-PCR clean up, the LCN method, and a reduced reaction volume with increased
      Taq DNA polymerase concentration. RESULTS: Using telogen hairs-a common source of
      LTDNA-and matched reference DNA, the LCN method produced the highest number of
      concordant and non-concordant (i.e., dropped-in) alleles. In comparison, the
      reduced reaction volume with increased Taq polymerase yielded more full and
      concordant DNA profiles (all alleles combined) and less off-ladder alleles from a
      broad range of input DNA. In addition, this method resulted in less non
      concordant alleles than LCN and no more than for standard PCR, which suggests
      that it may be preferred over increased PCR cycles for LTDNA analysis, either
      with or without consensus profiling and statistical modelling. CONCLUSIONS:
      Overall, this study highlights the importance and benefit of optimizing PCR
      conditions and developing improved laboratory methods to amplify and analyze
      LTDNA.

PMID- 25999134
TI  - Photoelectrochemical operation of a surface-bound, nickel-phosphine H2 evolution
      catalyst on p-Si(111): a molecular semiconductor|catalyst construct.
AB  - We demonstrate the covalent attachment and catalytic function of a nickel
      phosphine H2 evolution catalyst to a p-Si(111) photoelectrode. The covalently
      assembled semiconductor|molecular construct achieves a synergistic improvement
      (DeltaVonset = +200 mV) as compared to a solution of [(PNP)2Ni](2+) in contact
      with a p-Si(111)-CH3 photoelectrode. 

PMID- 25999133
TI  - An evidence-based guide to the investigation of sudden unexpected death in
      infancy.
AB  - PURPOSE: Many countries now have detailed investigations following sudden
      unexpected death in infancy (SUDI) but there is no clear evidence as to the most
      effective way to investigate SUDI. This systematic literature review addresses
      the following questions: What are the current models of practice for
      investigating SUDI? What is the evidence to support these investigative models?
      What are the key factors for effective SUDI investigation? METHODS: This was a
      systematic review of papers from Europe, North America, and Australasia,
      detailing models of SUDI investigation or the outcomes of SUDI investigations.
      RESULTS: The review includes data detailing four different models of
      investigation: police-led, coroner or medical examiner-led, healthcare-led or
      joint agency approach models. There were 18 different publications providing
      evidence of effectiveness of these models. All models, with the exception of
      police-led models, have the potential to reach best practice standards for SUDI
      investigation. Key factors identified for effective SUDI investigation include
      the need for mandatory investigation, strong leadership, integration with
      coronial services, and for investigations to be provided by specialist
      professionals. CONCLUSION: Detailed SUDI investigation should lead to greater
      understanding of why infants die and should help prevent future deaths. The
      challenge is now to ensure that local SUDI investigative practices are as
      effective as possible.

PMID- 25999135
TI  - Comparison of Coronary Atherosclerotic Plaque Burden and Composition of Culprit
      Lesions Between Cigarette Smokers and Non-Smokers by In Vivo Virtual Histology
      Intravascular Ultrasound.
AB  - Cigarette smoking is a major risk factor in the progression of atherosclerosis
      and has been shown to cause endothelial dysfunction, inflammation, and
      modification of lipid profile. However, its role in the pathogenesis of
      vulnerable coronary plaque remains unknown. We investigated the relationship
      between cigarette smoking and the development of vulnerable coronary artery
      plaque using virtual histology intravascular ultrasound (VH-IVUS). Data from
      consecutive patients who underwent VH-IVUS assessment of native coronary artery
      stenosis during clinically indicated cardiac catheterization at our institution
      over a 2-year period were analyzed. Baseline demographic and study
      characteristics were collected on all patients. Coronary plaque compositions of
      the culprit lesion were compared on bivariate and multivariate analysis. We
      analyzed data on 160 patients with a mean age of 60 +/- 11 years. Sixty-nine
      percent of these patients were admitted for acute coronary syndrome, 31% were
      smokers, and the mean plaque burden was 66%. On average, 58% of these plaques
      were fibrous, 19% were fibro-fatty, 18.3% had a necrotic core, and 5.4% were
      composed of dense calcium. Cigarette smokers had a higher burden of necrotic core
      (20.7% vs 17.2%; P=.04). On multivariate analysis, cigarette smoking was
      independently associated with a 4.54% increase in the burden of necrotic core
      (P=.01). Older age (>80 years) was also a predictor of higher necrotic core
      burden (P=.02). In conclusion, cigarette smoking is associated with a higher
      burden of necrotic core in coronary atherosclerotic plaques. This may represent
      one of the mechanisms for increased cardiovascular events. 

PMID- 25999136
TI  - Impact of Chronic Statin Therapy on Postprocedural Contrast-Induced Nephropathy
      in Patients Undergoing Non-Emergent Percutaneous Coronary Intervention.
AB  - BACKGROUND: Following percutaneous coronary intervention (PCI), elevations in
      serum creatinine level and declines in glomerular filtration rate are common.
      Prior studies have demonstrated benefit of chronic statin therapy in the
      prevention of contrast-induced nephropathy (CIN); however, it is unknown whether
      chronic statin therapy reduces the incidence of CIN in the non-emergent PCI
      setting. METHODS: Using the 2004-2005 Cornell Angioplasty Registry, a total of
      1171 consecutive patients were selected for analysis. The population was divided
      into two groups: (1) patients on chronic (>=30 days) statin therapy prior to PCI
      (n = 874); and (2) patients not on chronic statin therapy (n = 297). RESULTS:
      Patients taking chronic statin therapy were more likely to have diabetes mellitus
      (35.7% vs 22.6%; P<.001), previous myocardial infarction (36.3% vs 20.5%;
      P<.001), previous PCI (38.9% vs 16.2%; P<.001), and previous coronary artery
      bypass graft surgery (19.5% vs 11.4%; P=.01). Statin users were also more likely
      to be taking long-term aspirin (77.8% vs 59.6%; P<.001) and clopidogrel therapy
      (29.9% vs 14.1%; P<.001). Baseline serum creatinine levels were comparable
      between the two groups, as were procedural characteristics. The incidence of CIN
      following PCI was not significantly different between patients on chronic statin
      therapy versus those not on chronic statin therapy (4.2% vs 5.4%; P=.42).
      However, after multivariate adjustment, chronic statin therapy was associated
      with a lower incidence of CIN (odds ratio [OR], 0.21; 95% confidence interval
      [CI], 0.05-0.94; P=.04). Acute heart failure on admission and the urgency of the
      procedure (urgent vs elective PCI) were also independent predictors for
      developing CIN (OR, 3.04; 95% CI, 1.45-6.66 [P=.01] and OR, 2.80; 95% CI, 1.42
      5.55 [P=.01], respectively). Long-term mortality rates were similar between those
      on chronic statin therapy and those not on statins. CONCLUSION: CIN occurred in
      4.5% of patients following non-emergent PCI. Multivariate analysis demonstrated
      that chronic statin therapy decreased the odds of developing CIN in patients
      undergoing PCI.

PMID- 25999137
TI  - The Left Main Bifurcation Angle and Changes Throughout the Cardiac Cycle:
      Quantitative Implications for Left Main Bifurcation Stenting and Stents.
AB  - OBJECTIVE: The objective of this study was to quantify the left main (LM)
      bifurcation angles and their changes throughout the cardiac cycle. BACKGROUND: LM
      stenting is an accepted alternative to coronary artery bypass grafting. However,
      the LM bifurcation has great anatomic variability. Three-dimensional angles and
      their cyclic changes are important for coronary stenting. METHODS: Patients
      undergoing coronary computed tomography angiography (CCTA) for chest pain were
      scanned and analyzed in three-dimensional views for left main-left anterior
      descending (LM-LAD), left main-left circumflex (LM-LCX), and left anterior
      descending-left circumflex (LAD-LCX) angles and their cyclic changes.
      Calculations and assessment of angles, angular variability, and how these angles
      change throughout the cardiac cycle were analyzed. RESULTS: Forty-four patient
      scans were analyzed. The median end-diastolic LM-LCX angle was 130 degrees  and
      the LAD-LCX was 74 degrees . Median end-systolic angle for the LM-LCX was 133
      degrees , and LAD-LCX was 69 degrees . Large differences were found across all
      three absolute angles (LM-LCX, LAD-LCX, LM-LAD). Marked variability also occurred
      in how these angles changed throughout the cardiac cycle. CONCLUSIONS: LM
      bifurcation geometry in patients shows marked absolute angle variability, as does
      diastolic-systolic angle movement. LM bifurcation stents should accommodate wide
      interpatient bifurcation angles at rest for both the LM-LAD and LM-LCX angles.

PMID- 25999138
TI  - Myocardial Bridging: An Up-to-Date Review.
AB  - Myocardial bridging is a congenital anomaly in which a segment of a coronary
      artery takes a "tunneled" intramuscular course under a "bridge" of overlying
      myocardium. This causes vessel compression in systole, resulting in hemodynamic
      changes that may be associated with angina, myocardial ischemia, acute coronary
      syndrome, left ventricular dysfunction, arrhythmias, and even sudden cardiac
      death. While described on autopsy for centuries, technological advances such as
      coronary computed tomography angiography and intravascular ultrasound have
      contributed greatly to our understanding of the anatomic, hemodynamic, and
      pathophysiological consequences of systolic compression. Atherosclerosis
      preferentially develops immediately proximal to the bridged segment, likely due
      to alterations in shear stress, while the compressed segment itself is often
      spared. First-line therapy of symptomatic bridging remains medical treatment with
      beta-blockers and non-dihydropyridine calcium-channel blockers, and nitrates are
      contraindicated. Surgical myotomy, intracoronary stenting, and coronary artery
      bypass graft surgery have been used for refractory symptoms, but long-term
      outcomes remain uncertain. Further research is required to better define the
      patient population that would derive the greatest benefit from surgical and
      percutaneous intervention. 

PMID- 25999139
TI  - Atrial and Brain Natriuretic Peptide Secretion After Percutaneous Closure of the
      Left Atrial Appendage With the Watchman Device.
AB  - OBJECTIVE: To evaluate the effect of transcatheter closure of the left atrial
      appendage (LAA) with the Watchman device on the secretion of atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP). BACKGROUND: The LAA plays an
      important role in the regulation of intravascular volume via release of ANP and
      BNP. To date, there are no data suggesting substantial effects of hormonal
      interaction after percutaneous LAA closure for prevention of thromboembolic
      events in patients with non-valvular atrial fibrillation. METHODS: From October
      2009 until May 2010, transcatheter LAA closure using the Watchman device was
      performed in 31 patients with non-valvular atrial fibrillation. Venous blood
      samples were obtained before, immediately after device implantation, and prior to
      discharge for ANP and BNP measurements. RESULTS: LAA closure resulted in a
      significant increase in ANP and BNP levels immediately after the procedure
      compared with baseline measurements (ANP: from 241 +/- 34 pg/mL to 329 +/- 30
      pg/mL, P<.05; BNP: from 579 +/- 196 pg/mL to 698 +/- 211 pg/mL, P<.05), and a
      significant decrease prior to discharge compared with baseline values (ANP: from
      241 +/- 34 pg/mL to 149 +/- 30 pg/mL, P<.001; BNP: from 579 +/- 196 pg/mL to 429
      +/- 147 pg/mL, P<.001). CONCLUSIONS: These results suggest that percutaneous
      closure of the LAA results in an intermittent distribution of the vasoactive
      hormones ANP and BNP followed by a significant attenuation of ANP and BNP
      secretion in the early postprocedural period. The clinical impacts of these
      findings need to be evaluated in further studies.

PMID- 25999140
TI  - Pricing hospital care: Global budgets and marginal pricing strategies.
AB  - OBJECTIVE: The Canadian province of British Columbia (BC) is adding financial
      incentives to increase the volume of surgeries provided by hospitals using a
      marginal pricing approach. The objective of this study is to calculate marginal
      costs of surgeries based on assumptions regarding hospitals' availability of
      labor and equipment. DATA: This study is based on observational clinical,
      administrative and financial data generated by hospitals. Hospital inpatient and
      outpatient discharge summaries from the province are linked with detailed
      activity-based costing information, stratified by assigned case mix
      categorizations. STUDY DESIGN: To reflect a range of operating constraints
      governing hospitals' ability to increase their volume of surgeries, a number of
      scenarios are proposed. Under these scenarios, estimated marginal costs are
      calculated and compared to prices being offered as incentives to hospitals.
      PRINCIPAL FINDINGS: Existing data can be used to support alternative strategies
      for pricing hospital care. Prices for inpatient surgeries do not generate
      positive margins under a range of operating scenarios. Hip and knee surgeries
      generate surpluses for hospitals even under the most costly labor conditions and
      are expected to generate additional volume. CONCLUSIONS: In health systems that
      wish to fine-tune financial incentives, setting prices that create incentives for
      additional volume should reflect knowledge of hospitals' underlying cost
      structures. Possible implications of mis-pricing include no response to the
      incentives or uneven increases in supply.

PMID- 25999141
TI  - Water-assisted proton delivery and removal in bio-inspired hydrogen production
      catalysts.
AB  - Electrocatalysts for H2 production are envisioned to play an important role in
      renewable energy utilization systems. Nickel-based catalysts featuring pendant
      amines functioning as proton relays in the second coordination sphere of the
      metal center have led to catalysts achieving turnover frequencies as high as
      10(7) s(-1) for H2 production. The fastest rates are observed when water is
      present in solution, with rates up to 10(3) times faster than those found in dry
      solvent. The focus of this paper is to provide mechanistic insight into the
      unexpected enhancement due to water. Addition of H2 to [Ni(P(Cy)2N(R')2)2](2+)
      was previously shown to give three isomers of a Ni(0) product with two protonated
      amines, where the N-H can be endo or exo to the Ni. By investigating the
      deprotonation of these two N-protonated Ni(0) intermediates resulting from the
      addition of H2 to [Ni(P(Cy)2N(R')2)2](2+), we observe by NMR spectroscopy studies
      an enhancement in the rate of deprotonation for protons positioned on the pendant
      amine next to the metal (endo) vs. protons that are positioned away from the
      metal (exo). Computational studies suggest that for smaller bases, the
      desolvation energy of the exogenous base is the primary contribution limiting the
      rate of endo deprotonation, while steric accessibility and facile proton movement
      also contribute. For more bulky bases, steric accessibility can play the dominant
      role. The significant reduction in these barriers observed in the presence of
      water has important implications for disfavoring less productive catalytic
      pathways and increasing catalytic rates. 

PMID- 25999142
TI  - Candidate genes underlying heritable differences in reproductive seasonality
      between wild and domestic rabbits.
AB  - Reproductive seasonality is a trait that often differs between domestic animals
      and their wild ancestors, with domestic animals showing prolonged or even
      continuous breeding seasons. However, the genetic basis underlying this trait is
      still poorly understood for most species, and because environmental factors and
      resource availability are known to play an important role in determining breeding
      seasons, it is also not clear in most cases to what extent this phenotypic shift
      is determined by the more lenient captive conditions or by genetic factors. Here,
      using animals resulting from an initial cross between wild and domestic rabbits
      followed by two consecutive backcrosses (BC1 and BC2) to wild rabbits, we
      evaluated the yearly distribution of births for the different generations.
      Similar to domestic rabbits, F1 animals could be bred all year round but BC1 and
      BC2 animals showed a progressive and significant reduction in the span of the
      breeding season, providing experimental evidence that reduced seasonal breeding
      in domestic rabbits has a clear genetic component and is not a simple by-product
      of rearing conditions. We then took advantage of a recently published genome-wide
      scan of selection in the domesticated lineage and searched for candidate genes
      potentially associated with this phenotypic shift. Candidate genes located within
      regions targeted by selection include well-known examples of genes controlling
      clock functions (CRY1 and NR3C1) and reproduction (PRLR). 

PMID- 25999143
TI  - A High-Resolution Comparative Chromosome Map of Cricetus cricetus and Peromyscus
      eremicus Reveals the Involvement of Constitutive Heterochromatin in Breakpoint
      Regions.
AB  - Compared to humans and other mammals, rodent genomes, specifically Muroidea
      species, underwent intense chromosome reshuffling in which many complex
      structural rearrangements occurred. This fact makes them preferential animal
      models for studying the process of karyotype evolution. Here, we present the
      first combined chromosome comparative maps between 2 Cricetidae species, Cricetus
      cricetus and Peromyscus eremicus, and the index species Mus musculus and Rattus
      norvegicus. Comparative chromosome painting was done using mouse and rat paint
      probes together with in silico analysis from the Ensembl genome browser database.
      Hereby, evolutionary events (inter- and intrachromosomal rearrangements) that
      occurred in C. cricetus and P. eremicus since the putative ancestral Muroidea
      genome could be inferred, and evolutionary breakpoint regions could be detected.
      A colocalization of constitutive heterochromatin and evolutionary breakpoint
      regions in each genome was observed. Our results suggest the involvement of
      constitutive heterochromatin in karyotype restructuring of these species, despite
      the different levels of conservation of the C. cricetus (derivative) and P.
      eremicus (conserved) genomes.

PMID- 25999145
TI  - Oxaliplatin enhances gap junction-mediated coupling in cell cultures of mouse
      trigeminal ganglia.
AB  - Communications between satellite glial cells and neighboring neurons within
      sensory ganglia may contribute to neuropathic and inflammatory pain. To elucidate
      the role of satellite glial cells in chemotherapy-induced pain, we examined the
      effects of oxaliplatin on the gap junction-mediated coupling between these cells.
      We also examined whether the gap junction blocker, carbenoxolone, can reverse the
      coupling. Primary cultures of mice trigeminal ganglia, 24-48h after cell
      isolation, were used. Satellite glial cells were injected with Lucifer yellow in
      the presence or absence of oxaliplatin (60 MUM). In addition, the effect of
      carbenoxolone (100 MUM) on coupling, and the expression of connexin 43 proteins
      were evaluated. Dye coupling between adjacent satellite glial cells was
      significantly increased (2.3-fold, P<0.05) following a 2h incubation with
      oxaliplatin. Adding carbenoxolone to the oxaliplatin-treated cultures reversed
      oxaliplatin-evoked coupling to baseline (P<0.05). Immunostaining showed no
      difference between expression of connexin 43 in control and oxaliplatin-treated
      cultures. Our findings indicated that oxaliplatin-increased gap junction-mediated
      coupling between satellite glial cells in primary cultures of mouse trigeminal
      ganglia, and carbenoxolone reversed this effect. Hence, it is proposed that
      increased gap junction-mediated coupling was seen between satellite glial cells
      in TG. This observation together with our previous data obtained from a
      behavioral study suggests that this phenomenon might contribute to chemotherapy
      induced nociception following oxaliplatin treatment.

PMID- 25999144
TI  - Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP
      dependent Mkl1 signaling.
AB  - Radiotherapy is a standard treatment after conservative breast cancer surgery.
      However, cancers relapsing within a previously irradiated area have an increased
      probability to metastasize. The mechanisms responsible for this aggressiveness
      remain unclear. Here, we used the clinically relevant 4T1 breast cancer model
      mimicking aggressive local relapse after radiotherapy to identify differences
      between tumors grown in untreated versus preirradiated mammary glands. Tumors
      grown within preirradiated beds were highly enriched in transcripts encoding
      collagens and other proteins building or modifying the extracellular matrix, such
      as laminin-332, tenascins, lysyl oxidases and matrix metalloproteinases. Type I
      collagen, known to directly contribute to tissue stiffening, and the pro
      metastatic megakaryoblastic leukemia-1 (Mkl1) target gene tenascin-C were further
      investigated. Mammary tissue preirradiation induced Mkl1 nuclear translocation in
      the tumor cells in vivo, indicating activation of Mkl1 signaling. Transcript
      profiling of cultured 4T1 cells revealed that the majority of the Mkl1 target
      genes, including tenascin-C, required serum response factor (SRF) for their
      expression. However, application of dynamic strain or matrix stiffness to 4T1
      cells converted the predominant SRF/Mkl1 action into SAP domain-dependent Mkl1
      signaling independent of SRF, accompanied by a switch to SAP-dependent tumor cell
      migration. 4T1 tumors overexpressing intact Mkl1 became more metastatic within
      preirradiated beds, while tumors expressing Mkl1 lacking the SAP domain exhibited
      impaired growth and metastatic spread, and decreased Mkl1 target gene expression.
      Thus, we identified SAP-dependent Mkl1 signaling as a previously unrecognized
      mediator of aggressive progression of mammary tumors locally relapsing after
      radiotherapy, and provide a novel signaling pathway for therapeutic intervention.

PMID- 25999146
TI  - Tissue inhibitor of metalloproteases-4 (TIMP-4) modulates adipocyte
      differentiation in vitro.
AB  - Tissue inhibitors of metalloproteases (TIMPs) are multifunctional proteins that
      inhibit matrix metalloproteases (MMPs). The latest described member of the
      family, TIMP-4, is expressed mainly in adipose tissue, with detectable levels in
      the brain and heart. Besides its high expression in fat, the role of this
      inhibitor in adipose tissue is unknown. In order to study the role of TIMP-4
      during adipogenesis in vitro, 3T3-L1 cells were stably transfected with a TIMP-4
      specific shRNA or a control shRNA. Unexpectedly, upon TIMP-4 knockdown, 3T3-L1
      cells differentiated faster into mature adipocytes. To get better insight of TIMP
      4's role in adipogenesis, microarray expression analyses were performed. Network
      enrichment analyses uncovered 25 significant upstream signaling pathways, among
      which the NFkappaB cascade was found. Previous works have shown that NFkappaB is
      a key regulator of adipogenesis. In accordance, we found that TIMP-4 knockdown
      decreased NFkappaB activity during adipogenesis. The present work suggests that
      TIMP-4 might act as a negative regulator of adipogenesis through NFkappaB cascade
      modulation.

PMID- 25999148
TI  - Exploring the biology of the nail: An intriguing but less-investigated skin
      appendage.
AB  - The nail is a highly keratinized structure covering the tip of the digit, and
      considered to have several important functions in our daily life. In recent
      years, as biological aspects of the nail organ have been characterized, we
      realize that the nail unit and the hair follicle share various biological and
      immunological features. In particular, development and homeostasis of the nail
      unit also requires intimate epithelial-mesenchymal interactions that involve
      signaling pathways such as Wnt. There is also a striking immunological
      resemblance between both appendages, since the nail matrix, like the anagen hair
      bulb and the bulge, was shown to present unique characteristics of an immune
      privileged site. On the other hand, considerable progress in identifying nail
      stem cells has succeeded in locating putative stem cell niches in the nail unit.
      In this context, it is intriguing that nail stem cells residing in the nail
      matrix were recently shown to possess the ability to organize the process leading
      to digit regeneration. Further elucidation of signaling pathways governing
      epithelial-mesenchymal interactions in the nail unit seems to be a key to develop
      a novel therapeutic tool to treat amputees using nail epithelium. However, it is
      at least certain that the nail unit has a promising potential for the future of
      regenerative medicine. This review explores the biology of the nail organ by
      focusing on intriguing knowledge gained from recent studies. 

PMID- 25999147
TI  - Adaptation of HepG2 cells to a steady-state reduction in the content of protein
      phosphatase 6 (PP6) catalytic subunit.
AB  - Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an
      array of cellular processes. To assess the potential of PP6 as a therapeutic
      target in liver disorders, we attenuated expression of the PP6 catalytic subunit
      in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell
      lines (90% reduction of PP6-C protein content) were studied in depth. Both
      proliferated at a rate similar to control cells. However, flow cytometry
      indicated G2/M cell cycle arrest that was accounted for by a shift of the cells
      from a diploid to tetraploid state. PP6KD cells did not show an increase in
      apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or
      taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory
      signaling. Genes associated with DNA replication were downregulated. Mass
      spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides
      representing 56 proteins that were significantly affected by a stable reduction
      in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA
      splicing were overrepresented among these. PP6KD cells showed intact mTOR
      signaling. Our studies demonstrated involvement of PP6 in a diverse set of
      biological pathways and an adaptive response that may limit the effectiveness of
      targeting PP6 in liver disorders. 

PMID- 25999149
TI  - Whole-genome SNP genotyping mapped a novel locus for hereditary hypotrichosis on
      chromosome 2q31.1-q32.2.

PMID- 25999150
TI  - Response to Ho-Wan Ip and Chi-Chiu.

PMID- 25999151
TI  - Responsiveness of depression and its influence on surgical outcomes of lumbar
      degenerative diseases.
AB  - OBJECTIVE: To demonstrate the responsiveness of depression after surgery for
      lumbar degenerative disease and to verify the impact of this condition on
      surgical outcomes. PATIENT SAMPLE: A prospective cohort study with 91 patients
      with lumbar degenerative diseases who were evaluated preoperatively, at 30 days
      and 1 year postoperatively. OUTCOME MEASURES: Evolution of depression between the
      follow-ups and its correlation with satisfaction. METHODS: Depression was
      assessed with Beck Depression Inventory. According to depression responsiveness,
      patients were classified into four groups: NN = no depression; ND = normal during
      the preoperative period and depression within 1 year; DN = depression during the
      preoperative period and normal within 1 year; DD = depression during the
      preoperative period and within 1 year. RESULTS: Prevalence of preoperative
      depression was 28.6% and 17.6% within 1 year postoperatively. Most patients
      (65.4%) with depression in the preoperative period recovered postoperatively.
      Poor preoperative HRQoL measures were associated with higher rates of
      responsiveness of depression during the follow-up. Patients with depression at
      the 1-year postoperative follow-up had a worse functional outcome. Patients who
      improved from depression had similar outcome to those without depression.
      Dissatisfaction within 1 year postoperatively was greater in patients who become
      depressed after surgery and remain depressed at 1-year follow-up (NN = 8.8%; ND =
      42.9%; DN = 17.6%; DD = 44.4%; P = 0.012). CONCLUSION: Most patients with
      depression in the preoperative recover within 1 year postoperatively.
      Responsiveness of depression is associated with surgical outcomes. The presence
      of depression after the surgical treatment, independent of when it starts, had a
      major negative impact on prognosis.

PMID- 25999152
TI  - Involvement of a cyclic adenosine monophosphate-dependent signal in the diet
      induced canalicular trafficking of adenosine triphosphate-binding cassette
      transporter g5/g8.
AB  - The adenosine triphosphate-binding cassette (ABC) half-transporters Abcg5 and
      Abcg8 promote the secretion of neutral sterol into bile. Studies have
      demonstrated the diet-induced gene expression of these transporters, but the
      regulation of their trafficking when the nutritional status changes in the liver
      remains to be elucidated. Here, we generated a novel in vivo kinetic analysis
      that can monitor the intracellular trafficking of Abcg5/Abcg8 in living mouse
      liver by in vivo transfection of the genes of fluorescent protein-tagged
      transporters and investigated how hypernutrition affects the canalicular
      trafficking of these transporters. The kinetic analysis showed that lithogenic
      diet consumption accelerated the translocation of newly synthesized fluorescent
      tagged transporters to intracellular pools in an endosomal compartment and
      enhanced the recruitment of these pooled gene products into the bile canalicular
      membrane in mouse liver. Because some ABC transporters are reported to be
      recruited from intracellular pools to the bile canaliculi by cyclic adenosine
      monophosphate (cAMP) signaling, we next evaluated the involvement of this
      machinery in a diet-induced event. Administration of a protein kinase A
      inhibitor, N-(2-{[3-(4-bromophenyl)-2-propenyl]amino}ethyl)-5
      isoquinolinesulfonamide, decreased the canalicular expression of native
      Abcg5/Abcg8 in lithogenic diet-fed mice, and injection of a cAMP analog,
      dibutyryl cAMP, transiently increased their levels in standard diet-fed mice,
      indicating the involvement of cAMP signaling. Indeed, canalicular trafficking of
      the fluorescent-tagged Abcg5/Abcg8 was enhanced by dibutyryl cAMP administration.
      CONCLUSION: These observations suggest that diet-induced lipid loading into liver
      accelerates the trafficking of Abcg5/Abcg8 to the bile canalicular membrane
      through cAMP signaling machinery.

PMID- 25999153
TI  - Target of Rapamycin Complex 2 regulates cell growth via Myc in Drosophila.
AB  - Target of rapamycin (TOR) is an evolutionarily conserved serine/threonine protein
      kinase that functions as a central regulator of cellular growth and metabolism by
      forming two distinct complexes: TOR complex 1 (TORC1) and TORC2. As well as
      TORC1, TORC2 plays a key role in regulation of cell growth. But little is known
      about how TORC2 regulates cell growth. The transcription factor Myc also plays a
      critical role in cell proliferation and growth. Here we report that TORC2 and Myc
      regulate cell growth via a common pathway. Expression of Myc fully rescued growth
      defects associated with lst8 and rictor mutations, both of which encode essential
      components of TORC2. Furthermore, loss of TORC2 disrupted the nuclear
      localization of Myc, and inhibited Myc-dependent transcription. Together, our
      results reveal a Myc-dependent pathway by which TORC2 regulates cell growth. 

PMID- 25999154
TI  - Suicide note and the psychological autopsy: Associated behavioral aspects.
AB  - When a death occurs under traumatic, ambiguous, unknown, or uncertain
      circumstances, a death of suicidal origin can be considered. On many occasions, a
      suicide note is found next to body that helps to clarify certain aspects needed
      for the investigation to elucidate whether the death is really due to suicide or
      other causes. There are several types of suicide note (farewell, instructions,
      accusation of others, request for forgiveness, justification of one&#8217;s own
      suicide) that can contribute to the study of the victim&#8217;s psychological
      state and the circumstances that led to death. There is no unanimously approved
      way to conduct the psychological autopsy, but there are protocols for obtaining
      relevant information and preparing the report. 

PMID- 25999156
TI  - Parental rearing and eating psychopathology.
AB  - INTRODUCTION: The aim of the study was to identify the relationship between
      perceived rearing styles and the clinical expression of Eating Disorders (ED).
      METHODS: One hundred and ninety-six patients diagnosed of an ED and 127 healthy
      student as controls selected from the Nursing College were evaluated for general
      psychopathology (STAI, BDI II, RSE), and for abnormal eating attitudes (EAT, EDI
      II, BITE). The EMBU (&#8216;my memories of upbringing&#8217;) was administered
      for the assessment of perceived parental rearing styles and was used a
      questionnaire to assess familial variables. RESULTS: In relation to the control
      group, patients with ED perceived greater rejection, overprotection and less
      warmth than the controls. Patients who perceived greater paternal favoritism,
      maternal overprotection and low paternal emotional warmth, showed higher levels
      of anxiety. Paternal affection and maternal attitudes of rejection,
      overprotection and favoritism were related to lower self-esteem. Regarding
      abnormal eating attitudes, body dissatisfaction inversely correlated with
      paternal emotional care and maternal favoritism. The EDI subscales:
      ineffectiveness, perfectionism and ascetism were associated to parental
      rejection. Maternal rejection also related with drive for thinness, interoceptive
      awareness and impulse regulation. Perceived emotional warmth was related with
      perfectionism. Bulimia subscale and BITE scores were inversely associated to
      paternal overprotection and affection, and scored significantly higher in
      paternal favoritism and rejection from both parents. CONCLUSIONS: Perceived
      parental bonding is different in the various subtypes of EDs. Patients diagnosed
      of Bulimia Nervosa or Eating Disorders Not Otherwise Specified perceived greater
      rejection, less affection and a greater overprotection than Anorexia Nervosa
      patients and controls.

PMID- 25999155
TI  - Neurocognitive subtypes of schizophrenia.
AB  - OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and
      establish their association with clinical characteristics. METHODS: Sustained
      attention, executive function, facial emotion recognition, verbal learning, and
      working memory tests were applied to 253 subjects with schizophrenia. We
      identified neurocognitive subtypes by a latent class analysis of the tests
      results. After, we made a search for the association of these subtypes with
      clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1)
      &#8220;Global cognitive deficit&#8221;, 2) &#8220;Memory and executive function
      deficit&#8221;, 3) &#8220;Memory and facial emotion recognition deficit,&#8221;
      and 4) &#8220;Without cognitive deficit.&#8221; In comparison with the subtype
      &#8220;without cognitive deficit,&#8221; we found that the &#8220;memory and
      executive function deficit subtype&#8221; and the &#8220;global cognitive deficit
      subtype&#8221; had a higher frequency of male, unemployed, severe impairment, and
      adherence to treatment participants. However, in the &#8220;global cognitive
      deficit subtype&#8221; the differences were higher and there was also a lower
      frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The
      &#8220;memory and facial recognition deficit subtype&#8221; had a higher
      probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed
      (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past
      depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results
      suggest the existence of four neurocognitive subtypes in schizophrenia with a
      spectrum of dysfunction and severity. We found higher dysfunction in those with
      worse cognitive dysfunction, and higher affective psychopathology and less
      treatment adherence in those with less cognitive dysfunction.

PMID- 25999157
TI  - Validity evidence, sensibility and specificity of the severity dimension of the
      SDSS alcohol dependence scale.
AB  - OBJECTIVE: Therapeutic success in the treatment of alcohol use disorders highly
      depends on an appropriate diagnosis. The Substance Dependence Severity Scale
      &#8211;SDSS- is a scale that assesses substance dependence in dimensional terms
      and that follows the diagnostic criteria established by the international
      classification systems. The aim of this study is to provide validity evidence for
      the severity dimension of the alcohol dependence scale of the SDSS comparing it
      with the Mini International Neuropsychiatric Interview &#8211;MINI-, and others
      variables related to substance use included in the EuropASI. METHODS: A total of
      109 patients admitted for treatment in the Drug Abuse Center Services of Huelva
      who had used alcohol in the month previous to the interview participated. The
      SDSS, MINI and EuropASI were administered. The diagnostic capacity of the SDSS
      was assessed by Receiver Operating Characteristic (ROC) curve analysis, taking
      the MINI dependence diagnosis as standard. RESULTS: The area under the ROC curve
      (AUC) was 0.917 (CI=0.867-0.968). The trade-off between parameters was detected
      for a score of 9, with suitable values of sensitivity and specificity (83.58% and
      83.72%). CONCLUSIONS: The results support the use of the SDSS for the diagnosis
      of alcohol dependence and for assessment the severity of dependence.
      Administration of this scale makes it possible to obtain information, with a
      single score, on how severe the disorder is and whether the dependence criteria
      have been met.

PMID- 25999158
TI  - Substance Use among Medical Students: A Literature Review 1988- 2013.
AB  - The use of legal and illegal substances by medical students is a phenomenon that
      is only partially known. The aim of this paper was to review the literature
      published internationally in the last 25 years about the use of legal and illegal
      substances by medical students. A systematic search was made of MEDLINE and
      LILACS. One hundred and six manuscripts were evaluated, which included a
      population of 88,413 medical students. We validated 74,001 questionnaires, which
      represented 83.7% of responses. The methodology and the rigor of its application
      are not the same in all the publications. There are many regional variations,
      most studies being made in America and Europe. With the exception of alcohol in
      some areas of the Western world, medical students use substances less than
      university students in general and the general population. The substances used
      are mainly alcohol (24%), tobacco (17.2%), and cannabis (11.8%). The use of
      hypnotic and sedative drugs also is common (9.9%). The rate of use of stimulants
      is 7.7% and of cocaine, 2.1%; opiate use being very low (0.4%). In some parts of
      Latin America, up to 14.1% use inhalants. Students in the last years of school
      have a higher rate of substance use. The use of substances, except for hypnotics
      and sedatives, is more common among men than women. The use of substances by
      medical students is a phenomenon that should be evaluated systematically due to
      its prevalence and potential impact. 

PMID- 25999159
TI  - The symptom in the body. Monosymptomatic psychosis and hypochondriasis: A report
      of two cases.

PMID- 25999160
TI  - Preface. Special Issue on Proline-directed Foldases: Cell Signaling Catalysts and
      Drug Targets.

PMID- 25999161
TI  - Identification and mechanism of action analysis of the new PARP-1 inhibitor 2"
      hydroxygenkwanol A.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP-1) activity has been implicated
      in the pathogenesis of numerous diseases as cancer, inflammation, diabetes and
      neurodegenerative disorders, therefore the research for new PARP-1 inhibitors is
      still an active area. METHODS: To identify new potential PARP-1 inhibitors, we
      performed a screening of a small-molecule library consisting of polyphenols
      isolated from plants used in the traditional medicine, by Surface Plasmon
      Resonance (SPR). Biochemical and cellular assays were performed to confirm SPR
      results and select the promising candidate(s). Finally, limited proteolysis and
      ligand docking analyses allowed defining the protein region involved in the
      interaction with the putative inhibitor(s). RESULTS: The dimeric spiro-flavonoid
      2"-hydroxygenkwanol A, member of a relatively recently discovered class of
      flavonoids containing a spirane C-atom, has been identified as possible PARP-1
      inhibitor. This compound showed a high affinity for the polymerase (KD: 0.32+/
      0.05MUM); moreover PARP-1 activity in the presence of 2"-hydroxygenkwanol A was
      significantly affected both when using the recombinant protein and when measuring
      the cellular effects. Finally, our study suggests this compound to efficiently
      interact with the protein catalytic domain, into the nicotine binding pocket.
      CONCLUSION: 2"-hydroxygenkwanol A efficiently binds and inhibits PARP-1 at
      submicromolar concentrations, thus representing a promising lead for the design
      of a new class of PARP-1 modulators, useful as therapeutic agents and/or
      biochemical tools. GENERAL SIGNIFICANCE: Our study has identified an additional
      class of plant molecules, the spiro-biflavonoids, with known beneficial
      pharmacological properties but with an unknown mechanism of action, as a possible
      novel class of PARP-1 activity inhibitors.

PMID- 25999162
TI  - Quantification of speech-in-noise and sound localisation abilities in children
      with unilateral hearing loss and comparison to normal hearing peers.
AB  - The study objective was to quantify abilities of children with unilateral hearing
      loss (UHL) on measures that address known deficits for this population, i.e.
      speech understanding in quiet and noise, and sound localisation. Noise conditions
      varied by noise type and source location. Parent reports of real-world abilities
      were also obtained. Performance was compared to gender- and age-matched normal
      hearing (NH) peers. UHL performance was poorer and more varied compared to NH
      peers. Among the findings, age correlated with localisation ability for UHL but
      not NH participants. Low-frequency hearing in the better ear of UHL children was
      associated with performance in noise; however, there was no relation for NH
      children. Considerable variability was evident in the outcomes of children with
      UHL and needs to be understood as future treatment options are considered.

PMID- 25999163
TI  - Improvements in self-administration studies based on changes in skin button type
      and surgical technique.
AB  - INTRODUCTION: These studies, ranging in duration from 3 to 8months, evaluated the
      patency and longevity of the intravenous (IV) self-administration surgical model
      in male Sprague Dawley rats. Surgeries were categorized and assessed based on the
      number of catheter and/or skin button repairs required per animal across four
      separate self-administration studies. Design improvements in skin button types
      and changes in surgical procedures were chronologically tracked and assessed.
      METHODS: Animals were evaluated under a self-administration paradigm in which
      they were trained to respond for a food reward under a fixed ratio schedule (FR5
      or FR10). Animals were then surgically prepared with a femoral catheter and skin
      button port. Following recovery, animals were returned to food-maintained
      responding for at least 5 sessions and subsequently trained to respond for
      injections of a reinforcing drug. Once drug training criteria was established,
      the effects of vehicle or varying doses of test articles were evaluated. Animals
      were tested in operant chambers one hour each day 5days a week and the length of
      each study was recorded. Differences in the number of repairs per study as well
      as the total number of repairs were tabulated. RESULTS: Study length was directly
      correlated to the mean number of repairs occurring per study, with study length
      increasing as the total number of repairs increased. The majority of repairs were
      skin button-related issues. Multiple combinations of skin button types and
      surgical techniques were implemented across time to evaluate model efficiency and
      decrease overall cycle time per study. Initial combinations produced a greater
      number of repairs on a per study basis. However, the skin button type and
      surgical technique combination that resulted in the fewest number of total
      repairs used a lateral incision with a dorsal biopsy punch. DISCUSSION: The
      combination of improvements in skin button type and surgical techniques
      drastically decreased the number of surgical repairs required per study,
      increasing efficiency and thereby decreasing the overall cycle time for study
      completion.

PMID- 25999164
TI  - Impaired glucose metabolism in HIV-infected pregnant women: a retrospective
      analysis.
AB  - Metabolic complications, including diabetes mellitus, have been increasingly
      recognised in HIV-infected individuals since the introduction of antiretroviral
      therapy, particularly protease inhibitors (PIs). Pregnancy is also a risk factor
      for impaired glucose metabolism, and previous studies have given conflicting
      results regarding the contribution of PIs to impaired glucose tolerance (IGT) and
      gestational diabetes mellitus (GDM) in pregnant HIV-infected women. We conducted
      a retrospective review of all HIV-infected women attending a combined infectious
      disease and antenatal clinic between 2007 and 2013 who underwent a 100 g oral
      glucose tolerance test (OGTT) at 24-28 weeks. We grouped the patients based on
      whether their OGTT result was normal or abnormal, and compared the groups using
      standard parametric tests (t-test and Fisher's exact test). Of 263 women with HIV
      who attended the clinic, 142 (53.9%) attended for OGTT and were eligible for
      inclusion. The mean age was 31 years (SD 5.37), all women were of European or
      African origin and 33.7% had a body mass index >=30 kg/m(2) About 93.7% were on
      PI-based regimens. At delivery, the mean CD4 count was 526 cells/uL, and 13% of
      patients had a detectable viraemia. The prevalence of IGT was 2.8%, while the
      prevalence of GDM was 2.1%. Also, 71.4% (n = 5) of women with abnormal glucose
      metabolism were taking PIs versus 94.8% (n = 128) of normoglycaemic women (p =
      0.06). We did not confirm an increased rate of GDM in HIV-infected women in our
      patient population and found no association between PI use and GDM.

PMID- 25999165
TI  - Penile carcinoma presenting as inguinal bubo, masquerading as a venereal disease.
AB  - We report a case of penile carcinoma presenting as an inguinal bubo in a young
      man. The associated painful genital ulcer and history of high-risk sexual
      behaviour raised a strong suspicion of a sexually transmitted infection. We
      review the literature for similar cases, highlight the similarities with venereal
      disease and discuss the differential diagnosis of inguinal bubo. 

PMID- 25999166
TI  - The risk of non-melanoma skin cancer in HIV-infected patients: new data and meta
      analysis.
AB  - The role of HIV/AIDS in non-melanoma skin cancer (NMSC) is not well defined. We
      sought to update the evidence of the association between HIV/AIDS and risk of
      NMSC by gender and antiretroviral therapy (ART). We searched MEDLINE and EMBASE
      on 29 February 2014. Standardised incidence ratios with corresponding 95%
      confidence intervals were extracted and combined using generic inverse variance
      methods assuming a random effects model. Six studies including 78,794 patients
      with HIV/AIDS fulfilled the inclusion criteria. Analysis of all studies showed
      that HIV/AIDS was associated with an increased risk of NMSC (standardised
      incidence ratio 2.76; 95% confidence interval 2.55-2.98). The standardised
      incidence ratios of NMSC were 3.63 (1.08-12.22) for men and 2.18 (1.24-3.83) for
      women with HIV/AIDS, respectively. In analysis stratified by ART, we found that
      individuals receiving ART had lower risk of developing NMSC than individuals who
      had not received ART (standardised incidence ratio, 95% confidence interval; 1.95
      [1.10-3.47] versus 2.11 [1.44-3.12]). HIV/AIDS is associated with an increased
      risk of NMSC in both male and female patients. The use of ART appears to be
      beneficial in protecting against the development of NMSC.

PMID- 25999167
TI  - HIV research trials versus standard clinics for antiretroviral-naive patients:
      the outcomes differ but do the patients?
AB  - Exclusion criteria for HIV treatment-naive drug trials can be stringent and
      selection bias exists, making it difficult to extrapolate results into the 'real
      world' clinical situation. We aim to compare the demographics, virological
      outcomes and psychosocial complexity in adult HIV-infected treatment-naive
      patients from our cohort initiating combination antiretroviral therapy (cART) in
      research trials versus standard clinics. In our unit from 2006 to 2011, 1202
      standard clinic and 69 research trial patients initiated cART; every eighth
      standard clinics patient was included to create a standard clinics:research
      trials patient ratio of 2:1. Notes were retrospectively reviewed for patient
      demographics, attendance rates and virological outcomes. Data from 221
      antiretroviral-naive patients starting cART were analysed: 152 standard clinic
      patients and 69 from research trials. In the research trials group, there was an
      overrepresentation of men (p = 0.041), men who have sex with men (p < 0.001),
      patients of white ethnicity (p = 0.01), employed patients (p = 0.01) and patients
      using excessive alcohol (p = 0.02). There was equal representation of drug use,
      depression and referral to psychology, psychiatry and social work in both groups.
      The research trials group at baseline had significantly higher CD4 counts (p <
      0.001), lower viral loads (p = 0.01) and more patients achieved undetectable
      viral loads at three (p < 0.001), six (p < 0.001) and 24 months (p = 0.033).
      There is a prevailing common preconception that participants in clinical trials
      are uncomplicated, unlike their 'real-life' counterparts. We demonstrated
      important similarities in psychosocial complexity as well as differences in
      demographics and virological outcomes in trial and non-trial patients. Clinicians
      need to be aware of these discrepancies to ensure the facilitation of a
      heterogeneous population participating in research trials.

PMID- 25999168
TI  - HIV co-receptor tropism prediction remains stable over time in treatment-naive
      patients.
AB  - HIV co-receptor tropism determination is essential before prescribing the CCR5
      antagonist maraviroc. British HIV Association guidelines suggest tropism testing
      may remain valid for only 90 days in antiretroviral-naive patients. We aimed to
      determine the accuracy of this figure. Tropism was assessed in 26 antiretroviral
      naive patients with ongoing viral replication, sampled yearly from first clinic
      visit. The V3 region of HIV-1 was sequenced in triplicate, then tropism predicted
      using the Geno2Pheno system. Baseline tropism prediction remained valid for a
      median of 52 months (range 7-81). For 19/26 individuals baseline tropism remained
      unchanged throughout a median of 54 months follow-up; 18 R5 tropic and 1 X4
      tropic. In seven patients (27%) baseline tropism switched at least once (range 1
      4 switches) during follow-up; however, their baseline tropism prediction remained
      valid for a median of 45 months. Co-receptor tropism in treatment-naive patients
      with ongoing viral replication appears highly stable over time, suggesting that
      baseline genotypic tropism prediction may be valid for a longer duration in
      patients delaying ART initiation. In this study, baseline tropism prediction
      remained valid for a median of 52 months, suggesting current guidelines
      recommending repeat testing after 90 days may be excessively conservative in
      their assessment of tropism stability.

PMID- 25999169
TI  - Anaphylactic-like reaction from trimethoprim-sulfamethoxazole in a patient with
      AIDS.
AB  - We report a patient with AIDS who had an anaphylactic-like reaction from
      trimethoprim-sulfamethoxazole. Clinical suspicion of anaphylaxis should be
      considered in patients presenting with fever, hypotension, eosinophilia, rash,
      flushing or pulmonary infiltrates after initial exposure and re-exposure to the
      medication. This case highlights the need for healthcare professionals to be
      reminded of the association between this unusual antibiotic reaction resembling
      sepsis and HIV disease.

PMID- 25999170
TI  - Which sexually active female students get themselves tested for Chlamydia
      trachomatis? A cohort study.
AB  - Using data from the Prevention of Pelvic Infection (POPI) chlamydia screening
      trial, we compared the characteristics of female students who did or did not get
      tested for chlamydia outside the trial during 12 months' follow-up. Of the 2529
      women in the trial, we excluded 68 chlamydia positives in the intervention group
      who were referred for treatment at baseline. Of the remaining 2461 women, 1980
      (80%) answered the question about testing during follow-up on their 12 months'
      questionnaire and were included in the cohort. Of 1980 respondents, 529 (27%)
      reported having an independent chlamydia test, including 30 (48%) of 63 women
      with undiagnosed chlamydia at baseline. Predictors of testing included having
      undiagnosed chlamydia at baseline (adjusted odds ratio 2.44; 95% confidence
      interval 1.39-4.28), >=2 sexual partners in the year prior to baseline (OR 1.99;
      95% CI 1.60-2.48), history of sexually transmitted infection (1.63: 1.20-2.22);
      symptoms of pelvic discomfort, dyspareunia, abnormal vaginal discharge or inter
      menstrual bleeding (1.38; 1.09-1.73); and black ethnicity (1.37, 1.06-1.76).
      Although more women with risk factors got tested, half of women with undiagnosed
      chlamydia did not get tested. To optimise detection of chlamydia, testing should
      be offered routinely.

PMID- 25999172
TI  - Origin of D-amino acids detected in the acid hydrolysates of purified Escherichia
      coli beta-galactosidase.
AB  - In previous report, we detected D-amino acids in the acid hydrolysates of
      purified recombinant beta-galactosidase. Here, we employed a deuterium-hydrogen
      exchange method to discriminate innate D-amino acids from those generated during
      hydrolytic incubation. After hydrolysis of beta-galactosidase in DCl/D2O, amino
      acids were derivatized with NBD-F and separated on a reverse-phase column,
      followed by liquid chromatography-tandem mass spectrometry equipped with a chiral
      column. Our results show an absence of innate D-amino acid residues in the
      protein and suggest that the protein undergoes isomerization during a very early
      stage of hydrolytic incubation.

PMID- 25999173
TI  - Establishment and characterization of three embryonic cell lines of beet
      armyworm, Spodoptera exigua (Lepidoptera: Noctuidae).
AB  - Three cell lines (QAU-Se-E-1, -2 and -3, or Se-1, -2 and -3 for short) were
      established from eggs of beet armyworm (Spodoptera exigua) that have been
      passaged stably for more than 60 times in TNM-FH medium supplemented with 10 %
      fetal bovine serum. The cell lines consisted of round and spindle-shaped cells.
      The round cells accounted for 96.82, 84.34 and 83.16 % of the cells in the three
      cell lines, respectively, with cell diameters of 16.21 +/- 0.72, 15.63 +/- 0.58
      and 13.06 +/- 0.44 MUm. Random amplified polymorphic DNA and analysis of the CO I
      gene showed that the three cell lines were all derived from S. exigua. Growth
      curves at passage 30 were determined and the results showed that the cell
      population doubling times were 59.03, 49.08 and 49.91 h, respectively. The three
      cell lines can be infected by S. exigua multiple nucleopolyhedrovirus (SeMNPV).
      Se-3 was extremely susceptible to the virus with an infection rate of 97.52 % 4
      days after the inoculation and produced 2.02 * 10(6) OBs per mL of culture. Flow
      cytometry analysis showed that some of Se-1 and Se-2 cells had apoptosis after
      infection, whereas Se-3 cells did not. Bioassays showed that the virulence of the
      SeMNPV proliferated from Se-3 was similar to that from the insect with LC50 of
      5.55 * 10(5) and 2.64 * 10(5) OBs/mL. Therefore, the cell lines can be used to
      study the SeMNPV-host interactions and mechanisms underlying the interactions. 

PMID- 25999171
TI  - Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as
      cellular vaccines.
AB  - B-cells are promising candidate autologous antigen-presenting cells (APCs) to
      prime antigen-specific T-cells both in vitro and in vivo. However to date, a
      significant barrier to utilizing B-cells as APCs is their low capacity for non
      specific antigen uptake compared to "professional" APCs such as dendritic cells.
      Here we utilize a microfluidic device that employs many parallel channels to pass
      single cells through narrow constrictions in high throughput. This microscale
      "cell squeezing" process creates transient pores in the plasma membrane, enabling
      intracellular delivery of whole proteins from the surrounding medium into B-cells
      via mechano-poration. We demonstrate that both resting and activated B-cells
      process and present antigens delivered via mechano-poration exclusively to
      antigen-specific CD8(+)T-cells, and not CD4(+)T-cells. Squeezed B-cells primed
      and expanded large numbers of effector CD8(+)T-cells in vitro that produced
      effector cytokines critical to cytolytic function, including granzyme B and
      interferon-gamma. Finally, antigen-loaded B-cells were also able to prime antigen
      specific CD8(+)T-cells in vivo when adoptively transferred into mice. Altogether,
      these data demonstrate crucial proof-of-concept for mechano-poration as an
      enabling technology for B-cell antigen loading, priming of antigen-specific
      CD8(+)T-cells, and decoupling of antigen uptake from B-cell activation. 

PMID- 25999174
TI  - Effect of linear alkylbenzene sulfonate (LAS) on human intestinal Caco-2 cells at
      non cytotoxic concentrations.
AB  - Linear alkylbenzene sulfonate (LAS) is a cytotoxic synthetic anionic surfactant
      widely present in the environment due to its large-scale production and intensive
      use in the detergency field. In this study, we investigated the effect of LAS
      (CAS No. 25155-30-0) at non cytotoxic concentrations on human intestinal Caco-2
      cells using different in vitro bioassays. As results, LAS increased Caco-2 cell
      proliferation at concentrations ranging from 1 to 15 ppm, more significantly for
      shorter exposure time (24 h), confirmed using flow cytometry and trypan blue
      exclusion methods. Moreover, proteomics analysis revealed that this effect was
      associated with an over-expression of elongation factor 2 and dipeptidyl
      peptidase 3, and a down-regulation of 14-3-3 protein theta, confirmed at mRNA
      level using real-time PCR. These findings suggest that LAS at non cytotoxic
      concentrations, similar to those observed at wastewater treatment plants outlets,
      increases the growth rate of colon cancer cells, raising thereby its tumor
      promotion effect potential. 

PMID- 25999175
TI  - Duration of treatment in pulmonary tuberculosis: are international guidelines on
      the management of tuberculosis missing something?
AB  - BACKGROUND: Despite evidence of an association between tuberculosis (TB)
      treatment outcomes and the performance of national tuberculosis programmes (NTP),
      no study to date has rigorously documented the duration of treatment among TB
      patients. As such, this study was conducted to report the durations of the
      intensive and continuation phases of TB treatment and their predictors among new
      smear-positive pulmonary tuberculosis (PTB) patients in Malaysia. STUDY DESIGN:
      Descriptive, non-experimental, follow-up cohort study. METHODS: This study was
      conducted at the Chest Clinic of Penang General Hospital between March 2010 and
      February 2011. The medical records and TB notification forms of all new smear
      positive PTB patients, diagnosed during the study period, were reviewed to obtain
      sociodemographic and clinical data. Based on standard guidelines, the normal
      benchmarks for the durations of the intensive and continuation phases of PTB
      treatment were taken as two and four months, respectively. A patient in whom the
      clinicians decided to extend the intensive phase of treatment by >=2 weeks was
      categorized as a case with a prolonged intensive phase. The same criterion
      applied for the continuation phase. Multiple logistic regression analysis was
      performed to find independent factors associated with the duration of TB
      treatment. Data were analyzed using Predictive Analysis Software Version 19.0.
      RESULTS: Of the 336 patients included in this study, 261 completed the intensive
      phase of treatment, and 226 completed the continuation phase of treatment. The
      mean duration of TB treatment (n = 226) was 8.19 (standard deviation 1.65)
      months. Half (49.4%, 129/261) of the patients completed the intensive phase of
      treatment in two months, whereas only 37.6% (85/226) of the patients completed
      the continuation phase of treatment in four months. On multiple logistic
      regression analysis, being a smoker, being underweight and having a history of
      cough for >=4 weeks at TB diagnosis were found to be predictive of a prolonged
      intensive phase of treatment. Diabetes mellitus and the presence of lung cavities
      at the start of treatment were the only predictors found for a prolonged
      continuation phase of treatment. CONCLUSIONS: The average durations of the
      intensive and continuation phases of treatment among PTB patients were longer
      than the targets recommended by the World Health Organization. As there are no
      internationally agreed criteria, it was not possible to judge how well the
      Malaysian NTP performed in terms of managing treatment duration among PTB
      patients.

PMID- 25999176
TI  - The end effector of circadian heart rate variation: the sinoatrial node pacemaker
      cell.
AB  - Cardiovascular function is regulated by the rhythmicity of circadian, infradian
      and ultradian clocks. Specific time scales of different cell types drive their
      functions: circadian gene regulation at hours scale, activation-inactivation
      cycles of ion channels at millisecond scales, the heart's beating rate at
      hundreds of millisecond scales, and low frequency autonomic signaling at cycles
      of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock
      system: autonomic signaling from the brain releases neurotransmitters from the
      vagus and sympathetic nerves to the heart's pacemaker cells activate receptors on
      the cell. These receptors activating ultradian clock functions embedded within
      pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca2+ cycling,
      rhythmic ion channel current activation and inactivation, and rhythmic
      oscillatory mitochondria ATP production. Here we summarize the evidence that
      intrinsic pacemaker cell mechanisms are the end effector of the hierarchical
      brain-heart circadian clock system.

PMID- 25999177
TI  - Drosophila as a model for unfolded protein response research.
AB  - Endoplasmic Reticulum (ER) is an organelle where most secretory and membrane
      proteins are synthesized, folded, and undergo further maturation. As numerous
      conditions can perturb such ER function, eukaryotic cells are equipped with
      responsive signaling pathways, widely referred to as the Unfolded Protein
      Response (UPR). Chronic conditions of ER stress that cannot be fully resolved by
      UPR, or conditions that impair UPR signaling itself, are associated with many
      metabolic and degenerative diseases. In recent years, Drosophila has been
      actively employed to study such connections between UPR and disease. Notably, the
      UPR pathways are largely conserved between Drosophila and humans, and the
      mediating genes are essential for development in both organisms, indicating their
      requirement to resolve inherent stress. By now, many Drosophila mutations are
      known to impose stress in the ER, and a number of these appear similar to those
      that underlie human diseases. In addition, studies have employed the strategy of
      overexpressing human mutations in Drosophila tissues to perform genetic modifier
      screens. The fact that the basic UPR pathways are conserved, together with the
      availability of many human disease models in this organism, makes Drosophila a
      powerful tool for studying human disease mechanisms.

PMID- 25999178
TI  - Glyco-engineering strategies for the development of therapeutic enzymes with
      improved efficacy for the treatment of lysosomal storage diseases.
AB  - Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized
      by massive accumulation of undigested compounds in lysosomes, which is caused by
      genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently,
      enzyme replacement therapy has been successfully used for treatment of 7 LSDs
      with 10 approved therapeutic enzymes whereas new approaches such as
      pharmacological chaperones and gene therapy still await evaluation in clinical
      trials. While therapeutic enzymes for Gaucher disease have N-glycans with
      terminal mannose residues for targeting to macrophages, the others require N
      glycans containing mannose-6-phosphates that are recognized by mannose-6
      phosphate receptors on the plasma membrane for cellular uptake and targeting to
      lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic
      enzymes is essential for the clearance of accumulated compounds, the suitable
      glycan structure and its high content are key factors for efficient therapeutic
      efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting
      and tissue distribution have been highlighted. This review describes the glycan
      structures that are important for lysosomal targeting and provides information on
      recent glyco-engineering technologies for the development of therapeutic enzymes
      with improved efficacy.

PMID- 25999179
TI  - Stress-induced inhibition of LH pulses in female rats: role of GABA in arcuate
      nucleus.
AB  - Stress exerts profound inhibitory effects on reproductive function by suppression
      of the pulsatile release of GnRH and therefore LH. Besides the corticotrophin
      releasing factor (CRF), this effect also might be mediated via GABAergic
      signaling within the arcuate nucleus (ARC) since its inhibitory effects on LH
      pulses and increased activity during stress. In the present study, we
      investigated the role of endogenous GABAergic signaling within the ARC in stress
      induced suppression of LH pulses. Ovariectomised oestradiol-replaced rats were
      implanted with bilateral and unilateral cannulae targeting toward the ARC and
      lateral cerebral ventricle respectively. Blood samples (25 MUl) were taken via
      chronically implanted cardiac catheters every 5 min for 6 h for measurement of LH
      pulses. Intra-ARC infusion of GABAA receptor antagonist, bicuculline (0.2 pmol in
      200 nl artificial cerebrospinal fluid (aCSF) each side, three times at 20-min
      intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS;
      25 MUg/kg i.v.) but not restraint (1 h) stress on pulsatile LH secretion. In
      contrast, restraint but not LPS stress-induced suppression of LH pulse frequency
      was reversed by intra-ARC administration of GABABR antagonist, CGP-35348 (1.5
      nmol in 200 nl aCSF each side, three times at 20-min intervals). Moreover, intra
      ARC application of either bicuculline or CGP-35348 attenuated the inhibitory
      effect of CRF (1 nmol in 4 MUl aCSF, i.c.v.) on the LH pulses. These data
      indicate a pivotal and differential role of endogenous GABAA and GABAB signaling
      mechanisms in the ARC with respect to mediating immunological and psychological
      stress-induced suppression of the GnRH pulse generator respectively.

PMID- 25999180
TI  - Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by
      obesity.
AB  - Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known
      to traffic between high (HDM) and low (LDM) density microsomal fractions toward
      the plasma membrane (MF) under stimulation by insulin. However, its catalytic
      preference for aminoacyl substrates with N-terminal Leu or Cys is controversial.
      Furthermore, possible changes in its traffic under metabolic challenges are
      unknown. The present study investigated the catalytic activity attributable to EC
      3.4.11.3 in HDM, LDM and MF from isolated adipocytes of healthy (C), food
      deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates
      with N-terminal Cys or Leu, in absence or presence of insulin. Efficacy and
      reproducibility of subcellular adipocyte fractionation procedure were
      demonstrated. Comparison among HDM vs LDM vs MF intragroup revealed that
      hydrolytic activity trafficking from LDM to MF under influence of insulin in C,
      MSG and FD is only on N-terminal Cys. In MSG the same pattern of anterograde
      traffic and aminoacyl preference occurred independently of insulin stimulation.
      The pathophysiological significance of IRAP in adipocytes seems to be linked to
      comprehensive energy metabolism related roles of endogenous substrates with N
      terminal cysteine pair such as vasopressin and oxytocin. 

PMID- 25999181
TI  - [Mid-morning snack: is it important for a healthy diet?].

PMID- 25999182
TI  - In vitro protein profiles in the early and late stages of Douglas-fir
      xylogenesis.
AB  - The process of wood formation is of great interest to control and manipulate wood
      quality for economically important gymnosperms. A Douglas-fir tissue culture
      system was developed that could be induced to differentiate into tracheary
      elements (fibers) making it possible to monitor xylogenesis in vitro by a
      proteomics approach. Two proteomes were analyzed and compared, one from an early
      and one from a late stage of the fiber differentiation process. After 18 weeks in
      a differentiation-inducing medium, 80% of the callus cells were elongated while
      20% showed advanced spiral thickening indicating full wood fiber differentiation.
      Based on 2D electrophoresis, MS, and data analyses (data are available via
      ProteomeXchange with identifier PXD001484.), it was shown that in
      nondifferentiated callus (representing an early stage of development), proteins
      related to protein metabolism, cellular energy, and primary cell wall metabolism
      were abundant. By comparison, in cells actively differentiating wood fibers
      (representing a late stage of development), proteins involved in cell wall
      polysaccharide biosynthesis predominated together with housekeeping and stress
      associated proteins. 

PMID- 25999183
TI  - Effect of Aspirin Pretreatment or Slow Dose Titration on Flushing and
      Gastrointestinal Events in Healthy Volunteers Receiving Delayed-release Dimethyl
      Fumarate.
AB  - PURPOSE: In Phase III trials, delayed-release dimethyl fumarate (DMF; also known
      as gastro-resistant DMF) demonstrated significant efficacy and an acceptable
      safety profile in patients with relapsing-remitting multiple sclerosis. The
      purpose of the present study was to examine 2 potential mitigation strategies for
      flushing and gastrointestinal (GI) events associated with DMF treatment: aspirin
      (ASA) 325 mg pretreatment for flushing, and slow dose titration of DMF for
      flushing and GI events. METHODS: The 8-week study included 173 healthy volunteers
      randomized to 4 groups; 172 underwent dosing. The placebo group (n = 44) received
      placebo ASA 30 minutes before placebo DMF (weeks 1-4), then placebo DMF alone
      (weeks 5-8). The DMF without ASA group (n = 43) and the DMF with ASA group (n =
      43) received placebo ASA or ASA, respectively, 30 minutes before DMF (weeks 1-4),
      then DMF alone (weeks 5-8); in both groups, DMF was dosed at 120 mg BID (week 1)
      and 240 mg BID (weeks 2-8). The slow dose titration DMF group (n = 42) received
      DMF 120 mg once daily (week 1), 120 mg BID (week 2), 240 mg in the morning/120 mg
      in the evening (week 3), and 240 mg BID (weeks 4-8). Subjects recorded
      information about flushing and GI-related events by using an eDiary and numerical
      rating scales. FINDINGS: Flushing and GI-related events were reported in all
      groups and were mostly rated as mild or moderate in severity. Flushing events
      were generally ~1 hour in duration and, for most subjects with flushing,
      initially occurred the first day of study treatment. The duration of GI-related
      events and time to first GI-related event varied by event type. ASA reduced the
      incidence, severity, and number of flushing events without affecting duration or
      time to first flushing event, and had no adverse effect on GI-related events.
      Dose titration of DMF had no significant effect on flushing or GI events. No
      subjects discontinued the study due to flushing events. One subject (2%) in the
      placebo group, 3 subjects (7%) in the DMF without ASA group, 6 subjects (14%) in
      the DMF with ASA group, and 2 subjects (5%) in the slow dose titration DMF group
      discontinued treatment because of GI events. IMPLICATIONS: ASA pretreatment may
      mitigate flushing associated with DMF, with no adverse effect on GI events. Dose
      titration of DMF did not have a significant effect on flushing or GI events and
      is being evaluated further in ongoing clinical trials. ClinicalTrials.gov
      identifier: NCT01568112.

PMID- 25999184
TI  - Impact of Switching From an Initial Tumor Necrosis Factor Inhibitor on Health
      Care Resource Utilization and Costs Among Patients With Rheumatoid Arthritis.
AB  - PURPOSE: Despite improved clinical outcomes for the majority of patients, nearly
      30% of patients with rheumatoid arthritis (RA) who initiate tumor necrosis factor
      antagonist (anti-TNF) biologic agents fail to respond to their first-line anti
      TNF and switch to another anti-TNF or a non-TNF biologic. How this change affects
      health care costs and resource utilization is unknown. We therefore compared RA
      patients taking first-line anti-TNFs who switched to a second anti-TNF versus
      those patients who switched to an alternate biologic. METHODS: Health care claims
      data were obtained from a large US database for eligible adults with confirmed RA
      diagnoses who initiated anti-TNF treatment and switched to another biologic.
      Health care costs and utilization during the first 12 months' postswitch were
      compared. Generalized linear models were used to adjust for differences in
      demographic and clinical characteristics before switching. FINDINGS: Patients who
      switched to a second anti-TNF rather than a non-TNF biologic were generally
      younger (53.0 vs. 55.3 years; P < 0.0001) and less likely to be female (79.7% vs.
      82.7%; P = 0.0490). Of the 3497 eligible patients who switched from first-line
      anti-TNFs, 2563 (73.3%) switched to another anti-TNF and 934 (26.7%) switched to
      a non-TNF. Adalimumab was the most frequently prescribed (43.4%) second-line anti
      TNF, and abatacept was the most common non-anti-TNF (71.4%). Patients who
      switched to a second anti-TNF remained on their first medication for a
      significantly shorter period (342.5 vs 420.6 days; P < 0.0001) and had lower
      comorbidity indices and higher disease severity at baseline than those who
      switched to a non-anti-TNF. After adjusting for baseline differences, patients
      who switched to second anti-TNFs versus a non-TNF incurred lower RA-related costs
      ($20,938.9 vs $22,645.2; P = 0.0010) and total health care costs ($34,894.6 vs
      $38,437.2; P = 0.0010) 1 year postswitch. These differences were driven by
      increased physician office visit costs among the non-TNF group. IMPLICATIONS:
      Among the anti-TNF initiators who switched therapy, more patients switched to a
      second anti-TNF than to a non-TNF. Switching to a second anti-TNF treatment was
      associated with lower all-cause and RA-related health care costs and resource
      utilization than switching to a non-TNF. Because switching therapy may be
      unavoidable, finding a treatment algorithm mitigating this increase to any extent
      should be considered. These data are limited by their retrospective design.
      Additional confounding variables that could not be controlled for may affect
      results.

PMID- 25999186
TI  - Left atrial catheter ablation subsequent to Watchman(r) left atrial appendage
      device implantation: a single centre experience.
AB  - AIMS: Left atrial appendage device occlusion is an increasingly accepted therapy
      for stroke prevention in atrial fibrillation. The feasibility and safety of left
      atrial catheter ablation procedures in the presence of a left atrial appendage
      device implant is unclear. We report on 10 cases of successful left atrial
      catheter ablation therapy for atrial fibrillation in patients with an implanted
      Watchman(r) device. METHODS AND RESULTS: Consecutive patients with an existing
      Watchman(r) left atrial appendage implant and symptomatic antiarrhythmic-drug
      refractory atrial fibrillation or atrial tachycardias requiring left atrial
      catheter ablation therapy were included. Open irrigated tip ablation and circular
      mapping catheters were positioned in the left atrium via double transseptal
      access. Ten patients underwent successful left atrial geometry creation and
      complex atrial arrhythmia mapping and ablation in the presence of a chronically
      implanted Watchman(r) device. Arrhythmia targets included left atrial flutters, a
      focal tachycardia, left atrial CFAE zones, and pulmonary vein electrical
      isolation. The appearances of the Watchman(r) device position and device
      integrity were confirmed to be satisfactory in all patients at the end of the
      procedure based on fluoroscopy and intracardiac echocardiography imaging. There
      were no procedural complications. CONCLUSION: Left atrial catheter ablation
      therapy in the presence of an implanted Watchman(r) left atrial appendage
      occlusion device was efficacious and uncomplicated in our small single centre
      experience.

PMID- 25999185
TI  - Genetic encoding of the post-translational modification 2-hydroxyisobutyryl
      lysine.
AB  - We report the synthesis and genetic encoding of a recently discovered post
      translational modification, 2-hydroxyisobutyryl-lysine, to the genetic code of E.
      coli. The production of homogeneous proteins containing this amino acid will
      facilitate the study of modification in full-length proteins. 

PMID- 25999187
TI  - Predictors of left atrial volume index reduction following cryoballoon-based
      pulmonary vein isolation.
AB  - AIMS: Ablation for atrial fibrillation (AF) has been suggested to be associated
      with 'reverse left atrial remodelling'. Reduction in left atrial volume index
      (LAVIR) is regarded as a determinant of reverse remodelling following pulmonary
      vein isolation (PVI). However, there is paucity on data about the predictors for
      LAVIR after PVI. In this study, we aimed to investigate predictors of LAVIR at 12
      months in AF patients undergoing cryoballoon-based PVI. METHODS AND RESULTS:
      Patients with symptomatic paroxysmal or persistent AF despite >=1 antiarrhythmic
      drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the
      recent consensus recommendations, were enrolled and followed-up for 12 months in
      this prospective observational study. Left atrial volume was derived using the
      biplane area-length method. A total of 160 patients (54.25 +/- 7.66 years, 44.40%
      female) were involved in the study. Reduction in left atrial volume index
      occurred in 120 patients. Age [hazard ratio (HR): 0.901, 95% confidence interval
      (CI): 0.828-0.981, P = 0.017], hypertension (HR: 0.151, 95% CI: 0.048-0.471, P =
      0.001), mild mitral regurgitation (MR) (HR: 5.327, 95% CI: 1.489-19.058, P =
      0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005-0.065, P< 0.001) were found
      to be independent predictors for LAVIR. CONCLUSION: To the best of our knowledge,
      this is the largest study in the literature investigating the predictors of LAVIR
      following AF ablation. According to this data, younger patients without
      hypertension or moderate MR are most likely to experience LAVIR following
      ablation.

PMID- 25999188
TI  - Creating and sustaining healthy work environments.

PMID- 25999189
TI  - Hitting the nursing faculty shortage head on: strategies to recruit, retain, and
      develop nursing faculty.
AB  - More than ever before, schools of nursing are challenged with finding qualified
      faculty to teach growing numbers of undergraduate and graduate students.
      Qualified applicants by the thousands are being turned away, in large part
      because of an insufficient pipeline of faculty. This article describes how one
      school hit the shortage head on by creating alternate models for employing and
      growing new faculty, and then instituting a variety of strategies to develop and
      keep them. 

PMID- 25999190
TI  - Fundraising for Accelerated Study for the PhD in Nursing: A Community
      Partnership.
AB  - This article describes fundraising strategies by a School of Nursing to support a
      post-master's accelerated (3-year) PhD degree program. A sample proposal to
      solicit funds is included, as well as a contract that students sign before
      accepting the scholarship and agreeing to teach for 3 years or repay the money.
      The first campaign raised $2.3 million for ten students, and the second campaign
      raised $1.3 million for six students. One useful marketing strategy is to show
      the impact of an investment in educating ten doctoral students who will become
      faculty and teach 100 additional students per year, who will then become
      professionals caring for thousands of patients during their careers. Over a 10
      year period, the impact of an accelerated program is enormous, with 660 students
      taught who in their lifetime will care for 2.4 million patients. The article also
      discusses motivation and mind sets for giving to promote success in fundraising. 

PMID- 25999191
TI  - Barriers to integrating information technology content in doctor of nursing
      practice curricula.
AB  - To date, there is no benchmark data available on the measurement of program
      outcomes in doctor of nursing practice (DNP) programs. The purpose of this study
      was to identify barriers to integration of IT content in the curriculum in DNP
      programs, perceived IT competencies taught, and DNP faculty perception of
      competencies. The study location was DNP programs in the United States, and focus
      was on doctorate-prepared faculty with a DNP or PhD. A descriptive design using
      an Internet-based survey was done with 113 DNP programs administrators and
      faculty across the United States. Limitation of the study was that few DNP
      administrators forwarded the study to faculty, limiting the sample size. For the
      purpose of this study, the results were limited to responses from DNP
      administrators, and some comparative data of the faculty were used. Barriers
      measured included lack of qualified faculty, faculty's limited knowledge or
      skills in IT, lack of interest, age, lack of time to learn IT, lack of time to
      use IT, too many work demands, lack of administrative vision, unclear
      expectations of faculty, lack of technical support to faculty, or lack of
      resources. Leading barriers to IT implementation were lack of time of faculty,
      too many other work demands of faculty, lack of resources dedicated to IT, and
      lack of qualified faculty to teach IT. Further research is necessary on doctorate
      prepared faculty and on interventions to overcome these barriers is needed. 

PMID- 25999192
TI  - Using implementation science as the core of the doctor of nursing practice
      inquiry project.
AB  - New knowledge in health care needs to be implemented for continuous practice
      improvement. Doctor of nursing practice (DNP) programs are designed to increase
      clinical practice knowledge and leadership skills of graduates. This article
      describes an implementation science course developed in a DNP program focused on
      advancing graduates' capacity for health systems leadership. Curriculum and
      course development are presented, and the course is mapped to depict how the
      course objectives and assignments were aligned with DNP Essentials. Course
      modules with rational are described, and examples of how students implemented
      assignments are provided. The challenges of integrating this course into the life
      of the school are discussed as well as steps taken to develop faculty for this
      capstone learning experience. This article describes a model of using
      implementation science to provide DNP students an experience in designing and
      managing an evidence-based practice change project. 

PMID- 25999193
TI  - Perceived importance of teaching characteristics in clinical nurse specialist
      preceptors.
AB  - Advanced practice nursing education includes a minimum of 500 hours of supervised
      clinical practicum, with practicing clinicians serving as preceptors providing
      the bulk of the supervision. Preceptor behaviors and teaching skills can
      significantly impact student learning, however, no empirical evidence exists that
      identifies or evaluates effective clinical teaching characteristics in clinical
      nurse specialist (CNS) preceptors. PURPOSE: The purpose of this study was to
      explore and compare CNS student and preceptor perceptions of the importance of
      clinical teaching characteristics in CNS preceptors. METHODS/SAMPLE: Data was
      obtained from CNS preceptors (n = 278) and CNS students (n = 78) through a web
      based questionnaire instrument. Twenty-one previously identified effective
      clinical teaching characteristics served as the questionnaire items and
      participants were asked to rate their importance and identify the most and least
      important characteristic. Statistical tests including calculation of mean scores
      and independent t-tests for each characteristic were completed. FINDINGS: The CNS
      preceptors and students rated all effective teaching characteristics as
      important. Clinical competence/judgment was identified as the most important
      characteristic among participants. The findings demonstrated congruence between
      students' and preceptors' ratings except for the characteristics calm during
      times of stress and flexibility. CONCLUSIONS: These findings can help CNS faculty
      and practicing CNSs better prepare and evaluate preceptors for supporting
      advanced practice students in clinical practicum experiences.

PMID- 25999194
TI  - Accelerated Master's Programs in Nursing for Non-Nurses: An Integrative Review of
      Students' and Faculty's Perceptions.
AB  - Accelerated master's programs in nursing for non-nurses (AMPNNNs) are rapidly
      increasing in number. They offer accelerated entry into nursing practice for
      individuals with a baccalaureate degree or higher. An integrative review, based
      on Whittemore and Knafl (2005) was conducted to identify the characteristics of
      the students and the perceptions of students, graduates, and faculty who
      participate in these programs. A search of published literature yielded 15
      sources with relevant data for this integrative review. Student characteristics
      indicate predominantly Caucasian females who are older, mature, and academically
      accomplished. There is a dearth of literature related to the perceptions of
      students and faculty as they experience the program. Student experienced role
      changes, and the demands of nursing education were notable. Faculty identified
      the need to develop innovative teaching strategies for adult learners. The gaps
      in the evidence base of AMPNNNs are highlighted, and areas for future research
      are recommended. 

PMID- 25999195
TI  - Describing a residency program developed for newly graduated nurse practitioners
      employed in retail health settings.
AB  - Retail health clinics are an expanding health care delivery model and an emerging
      new practice site for nurse practitioners (NPs). Critical thinking skills,
      clinical competence, interprofessional collaboration, and business savvy are
      necessary for successful practice in this highly independent and autonomous
      setting. This article describes a pilot residency partnership program aimed at
      supporting new graduate NP transition to practice, reducing NP turnover, and
      promoting academic progression. Eight new graduate NPs were recruited to the
      pilot and paired with experienced clinical NP preceptors for a 12-month program
      that focused on increasing clinical and business competence in the retail health
      setting. The residency program utilized technology to facilitate case conferences
      and targeted Webinars to enhance learning and peer-to-peer sharing and support.
      An on-line doctoral-level academic course that focused on interprofessional
      collaboration in health care, population health, and business concepts was
      offered. Both NPs and preceptors were highly satisfied with the academic-service
      residency program between MinuteClinic and Northeastern University School of
      Nursing in Boston, MA. New NPs particularly valued the preceptor model, the
      clinical case conferences, and business Webinars. Because their priority was in
      gaining clinical experience and learning the business acumen relevant to managing
      the processes of care, they did not feel ready for the doctoral course and would
      have preferred to take later in their practice. The preceptors valued the
      academic course and felt that it enhanced their precepting and leadership skills.
      At the time of this article, 6 months post completion of the residency program,
      there has been no turnover. Our experience supports the benefits for residency
      programs for newly graduated NPs in retail settings. The model of partnering with
      academia by offering a course within a service organization's educational
      programs can enable academic progression.

PMID- 25999196
TI  - The creation of a synchronous learning environment to support a study abroad
      program for nursing majors at a traditional liberal arts university.
AB  - In response to an increased need for Spanish-speaking and culturally competent
      nurses, a small private undergraduate-only liberal arts university implemented a
      semester-long study abroad program for nursing majors in Barcelona, Spain. Prior
      to the creation of this program, study abroad for nursing students was limited
      because of prelicensure requirements and limitations of a traditional nursing
      curriculum. Students studying in Spain enroll in four courses--including two core
      nursing courses delivered using Polycom hardware and telepresence software by
      nursing faculty who remain in the United States, a Spanish language course, and
      one general education course taught either by the University's Spain Director or
      by an experienced Spanish professor. Participants live with host families and
      participate in clinical and community observational experiences in Spanish health
      care agencies. Students then complete direct patient care requirements upon
      return to the United States. To our knowledge, no other undergraduate-only
      institution offers a semester-long study abroad experience for nursing majors
      embedded within the curriculum using synchronous learning; we believe our Spain
      program, which is in its fourth year being open to nursing majors, is truly an
      innovative approach to establish cultural competence for undergraduate nursing
      majors that could serve as a model for other schools of nursing and health
      disciplines.

PMID- 25999197
TI  - International service-learning: an opportunity to engage in cultural competence.
AB  - One-day international service-learning projects are an opportunity for nursing
      students to engage in learning cultural awareness, knowledge, and skills. At XXX
      University, faculty developed these international service-learning projects in
      Mexico where students participated in health promotion teaching for children and
      families and providing health care for older adults. The purpose of this article
      is to describe 3 types of student experiences gained during 1-day international
      service-learning projects. We named these experiences cultural communication,
      cultural confidence, and cultural surprise. 

PMID- 25999198
TI  - Identification and support of at-risk students using a case management model.
AB  - This study evaluated a program to identify and support students at risk for
      failure in nursing courses or NCLEX-RN. A case management model (CMM) was
      implemented to provide assessment of and support for 183 bachelor of science in
      nursing students; 83 were identified as at risk by the CMM criteria. The CMM
      involved student self-evaluation and grade assessment of prerequisite and nursing
      courses. Science course grades were all found to be significantly higher for
      those students who passed NCLEX-RN on the first attempt than those who did not.
      Admission GPA was significant (t=2.443, P=.018). Using a Motivated Strategies for
      Learning Questionnaire for self-evaluation, at-risk students rated their
      performance in nursing courses higher in every area than the non-at-risk student
      group, significantly higher for self-efficacy (t = 2.829, P=.005) and
      metacognition (t =2.426, P=.016). Neither task value nor critical thinking scores
      were significant. Graduation rate was 100% with 158 students passing NCLEX-RN on
      the first attempt (64 of 83 at risk and 94 of 100 non-at risk). The CMM was
      effective in identification and support of at-risk students. 

PMID- 25999199
TI  - Relationship between the knowledge, attitude, and self-efficacy on sexual health
      care for nursing students.
AB  - Promoting patients' sexual health for better quality of life is an important task
      for nurses. Little is known about the factors impacting nursing students to
      better prepare for the future nursing practice on sexual health care. The purpose
      of the study is to address the need for nursing education on sexuality by
      exploring the relationship between nursing students' knowledge, attitude, and
      self-efficacy for patients' sexual health care. A total of 190 senior nursing
      students were purposely enrolled to the study by answering a self-report
      questionnaire, and the data were analyzed using structural equation modeling
      (SEM). The results demonstrated positive correlation of the relationship between
      knowledge of sexual health care (KSH) and attitude to sexual health care (ASH;
      gamma = .35, t = 3.31, P < .001), the relationship between KSH and self-efficacy
      for sexual health care (SESH; gamma = .29, t = 2.98, P < .01), and relationship
      between ASH and SESH (gamma = .34, t = 4.30, P < .001). Therefore, nursing
      educators need not only provide students the knowledge and skills on sexual
      health care but also educate them about positive attitudes on sexuality to
      enhance their efficacy to deal with the patients' sexuality matters in the future
      nursing practice. 

PMID- 25999200
TI  - A longitudinal study on the effect of tailored training and counseling on the
      professional attitude of nursing students.
AB  - The development of professional attitudes in nursing students is influenced by
      their learning experiences (knowledge, skills, and attitudes) and instructors'
      professional behaviors. Instructors can enhance students' professional attitude
      by organizing the training environment, being a role model, and providing
      counseling. This study was conducted as a tailoring intervention study over 4
      years (2010-2013) examining 73 nursing students (34 intervention, 39 control) to
      determine the effect of training and counseling on nursing students' professional
      attitudes. Data were collected utilizing the Introductory Characteristics Form
      and the Instrument of Professional Attitude for Student Nurses. Intervention
      group students were provided training and counseling complementing their current
      education to develop their professional attitudes. Controls proceeded with their
      current education. Instrument for Professional Attitude for Student Nurses
      posttest scores of the intervention group were significantly higher than those of
      control group students. Furthermore, intervention group scores on all subscales
      other than "competence and continuous education" significantly increased after
      training. Controls showed no growth in professional attitudes, other than in
      "contribution to scientific knowledge." The training and counseling program had a
      positive influence on the professional attitudes of nursing students. Thus,
      providing tailored training and counseling associated to professionalism
      throughout the educational process at schools providing nursing training is
      recommended. 

PMID- 25999201
TI  - Cluster Randomized Controlled Trial of Intervention to Increase Participant
      Retention and Completed Home Visits in the Nurse-Family Partnership.
AB  - We conducted a cluster-based randomized controlled trial of an intervention
      designed to improve participant retention in community replication sites of the
      Nurse-Family Partnership (NFP). We registered 26 sites and randomized them into
      three groups: retention intervention (RI, N = 9), delayed RI (DRI, N = 6), or
      control (C, NFP as usual, N = 11). The RI consisted of training nurses to give
      more explicit control over the frequency of visits and content of the program to
      the parent participants. Two of the sites assigned to the RI, two assigned to the
      DRI, and two out of four nurses in one other site assigned to the DRI chose not
      to participate in the intervention. Primary analyses (intention to treat)
      contrasted changes in participant retention and completed visits (the primary
      outcomes) in the two intervention groups (RI and DRI) compared to control sites,
      focusing on differences in performance among baseline cohorts compared to cohorts
      enrolled during the first year during which the retention intervention was
      implemented. Compared to baseline, retention declined in the control sites over
      time but stayed the same in the RI and DRI sites (p value for interaction =
      0.099). Compared to baseline, the number of completed home visits declined over
      time in the control sites but did not in the RI and DRI sites, producing a
      significant treatment difference in change in mean completed home visits over
      time (2.71 visits, SE = 1.164, p = 0.020). The intervention offset a decline over
      time in retention and completed home visits found in the control group during the
      time covered by this trial. Quantitative and qualitative evaluation of the
      intervention indicated that improvements are needed to promote its uptake.

PMID- 25999202
TI  - Acylated glucosylflavones as alpha-glucosidase inhibitors from Tinospora crispa
      leaf.
AB  - The ethanolic extract of Tinospora crispa leaf had shown inhibitory activity
      toward alpha-glucosidase. Bioassay guided fractionation and separation of this
      extract led to the isolation of 17 flavonoids. Among them, four acylated
      glycosylflavonoids (6, 8, 9, 15) are new compounds. Their structures were
      elucidated on the basis of spectroscopic analysis. Among the isolated compounds,
      isovitexin 2"-(E)-p-coumarate (8) showed the best activity against alpha
      glucosidase with an IC50 value of 4.3+/-1.4MUM. However, isoorientin 2"-(E)-p
      coumarate (7), the 3'-hydroxylated 8, is much less active (IC50 35.7MUM). Such
      significant difference was rationalized by CAD study on alpha-glucosidase.

PMID- 25999203
TI  - Optimization of rhodanine scaffold for the development of protein-protein
      interaction inhibitors.
AB  - Searching for novel protein-protein interactions inhibitors (PPIs) herein we
      describe the identification of a new series of rhodanine derivatives. The
      selection was performed by means virtual-screening, docking studies, Molecular
      Dynamic (MD) simulations and synthetic approaches. All the new obtained compounds
      were tested in order to evaluate their ability to inhibit the interaction between
      the HIV-1 integrase (IN) enzyme and the nuclear protein lens epithelium growth
      factor LEDGF/p75.

PMID- 25999204
TI  - Synthesis and antiprotozoal activity of mono- and bis-uracil isatin conjugates
      against the human pathogen Trichomonas vaginalis.
AB  - A library of mono- and bis-uracil isatin conjugates were synthesized and
      subjected for the assessment of their in vitro activity against the protozoal
      pathogen Trichomonas vaginalis. The structure activity studies (SAR) revealed
      that the bis-uracil-isatin based conjugates were more effective than their
      corresponding mono conjugates in inhibiting the growth of T. vaginalis at
      approximately 10 MUM with no visual effect on mammalian cells at the same
      concentration.

PMID- 25999205
TI  - In silico evaluation of human small heat shock protein HSP27: homology modeling,
      mutation analyses and docking studies.
AB  - Small heat-shock proteins, possessing chaperone-like activity, represented
      crucial proteins actively involved in maintain protein homeostasis, which act to
      prevent improper polypeptide aggregation and deposition of misfolded proteins. In
      this context, a number of mutations concerning the HspB1 protein proved to be
      associated with the development of several neuropathologies. Unfortunately,
      molecular mechanisms underlying the onset of these diseases and in particular the
      changes induced by the mutations in HspB1 structure, remain poorly characterized.
      On the other hand, more recent studies demonstrated that HspB1 overexpression
      leads to an overactive chaperone activity, which in turn contributes to the
      anticancer agent resistance. On these basis, Hsp27 could represent a good
      innovative target for development of novel cancer therapy. Therefore, in this
      work a computational study, based on the homology model of the complete Hsp27
      protein and of several pathological mutant forms, was developed. Finally, the
      derived model was employed to perform, for the first time, docking simulations on
      a recently identified Hsp27 inhibitor, disclosing a new useful panorama to be
      exploited for the further development of new compounds.

PMID- 25999206
TI  - Anti-MRSA activity of isoplagiochin-type macrocyclic bis(bibenzyl)s is mediated
      through cell membrane damage.
AB  - We synthesized three geometrical isomers of a macrocyclic bis(bibenzyl) based on
      isoplagiochin, a natural product isolated from bryophytes, and evaluated their
      antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti
      MRSA activity). The isomer containing a 1,4-linked ring (5) showed only weak
      activity, whereas the isomers containing a 1,3-linked (6) or 1,2-linked (7) C
      ring showed potent anti-MRSA activity. Molecular dynamics calculations indicated
      that these differences are probably due to differences in the conformational
      flexibility of the macrocyclic ring; the active compounds 6 and 7 were more rigid
      than 5. In order to understand the action mechanism of anti-MRSA activity, we
      investigated the cellular flux of a fluorescent DNA-binder, ethidium bromide
      (EtBr), in the presence and absence of these macrocycles. The active compound 6
      increased the levels of EtBr inflow and outflow in S. aureus cells, as did our
      potent anti-MRSA riccardin derivative (4), indicating that these compounds
      increased the permeability of the cytoplasmic membrane. Inactive 5 had no effect
      on EtBr inflow or outflow. Furthermore, compound 6 abrogated the normal
      intracellular concentration gradients of Na(+) and K(+) in S. aureus cells,
      increasing the intracellular Na(+) concentration and decreasing the K(+)
      concentration, while 5 had no such effect. These results indicate that anti-MRSA
      active macrocyclic bis(bibenzyl) derivatives directly damage the gram-positive
      bacterial membrane, resulting in increased permeability.

PMID- 25999207
TI  - Comments on "In vivo post-contrast 1H-MRS evaluation of malignant and benign
      breast lesions: a meta-analysis".

PMID- 25999208
TI  - Inhibitors of Matriptase-2 Based on the Trypsin Inhibitor SFTI-1.
AB  - A series of 17 new analogues of trypsin inhibitor SFTI-1 were designed and
      synthesized to obtain matriptase-2 inhibitors. A number of the modified bicyclic
      peptides displayed much higher affinity towards matriptase-2 than towards the
      highly homologous matriptase-1. Replacement of Lys5 by Arg in the wild-type SFTI
      1 led to an 11-fold increase in the matriptase-2 inhibitory activity. Replacement
      of Arg2 by its enantiomer (D-arginine) slightly lowered the inhibition of
      matriptase-2, but almost completely abolished the affinity towards matriptase-1,
      thus yielding the most selective matriptase-2 inhibitor. This is the first report
      describing inhibitors of the recently discovered matriptase-2 based on the SFTI-1
      structure. The results showed that SFTI-1 is a promising scaffold for the design
      of potent and selective inhibitors of this enzyme. 

PMID- 25999209
TI  - Immunological markers predict the prognosis of patients with squamous non-small
      cell lung cancer.
AB  - Lung cancer has become the leading cause of cancer-related death worldwide.
      However, treatment failures still represent enormous challenges, and it is
      doubtful whether standard treatment modalities could continuously achieve
      substantial improvements. As one of the novel therapy strategies, PD-L1 has been
      shown the function of down-regulating T cell activation through receptor PD-1.
      Moreover, prognosis of cancer patients is based not only on tumor-related factors
      but also on host-related factors, particularly systemic inflammatory response.
      Significantly, squamous non-small cell lung cancer (NSCLC) revealed to be
      divergent clinical and molecular phenotypes compared with non-squamous NSCLC.
      Monocyte ratio, neutrophils to lymphocytes ratio, PD-L1 immunostaining score and
      PD-1-positive stained tumor-infiltrating lymphocyte counts were assessed by
      Fisher's linear discriminant analysis to discriminate whether overall survival
      (OS) would exceeding 5 years. Finally, a prediction model was established for OS
      based on these immunological markers. Furthermore, this prediction model was
      validated in a second set of squamous NSCLC patients. The model offers a novel
      tool for survival prediction and could have important clinical implications for
      patients with squamous NSCLC, thus providing a framework for future
      individualized therapy.

PMID- 25999210
TI  - Posterior reversible encephalopathy syndrome--Insight into pathogenesis, clinical
      variants and treatment approaches.
AB  - Posterior reversible encephalopathy syndrome is a rare clinicoradiological entity
      characterized by typical MRI findings located in the occipital and parietal
      lobes, caused by subcortical vasogenic edema. It was first described as a
      distinctive syndrome by Hinchey in 1996. Etiopathogenesis is not clear, although
      it is known that it is an endotheliopathy of the posterior cerebral vasculature
      leading to failed cerebral autoregulation, posterior edema and encephalopathy. A
      possible pathological activation of the immune system has been recently
      hypothesized in its pathogenesis. At clinical onset, the most common
      manifestations are seizures, headache and visual changes. Besides, tinnitus and
      acute vertigo have been frequently reported. Symptoms can be reversible but
      cerebral hemorrhage or ischemia may occur. Diagnosis is based on magnetic
      resonance imaging, in the presence of acute development of clinical neurologic
      symptoms and signs and arterial hypertension and/or toxic associated conditions
      with possible endotheliotoxic effects. Mainstay on the treatment is removal of
      the underlying cause. Further investigation and developments in endothelial cell
      function and in neuroimaging of cerebral blood flow are needed and will help to
      increase our understanding of pathophysiology, possibly suggesting novel
      therapies. 

PMID- 25999211
TI  - Short-term effects of calcium ions on the apoptosis and onset of mineralization
      of human dental pulp cells in vitro and in vivo.
AB  - Calcium ions (Ca2+) are a major constituent of most pulp-capping materials and
      have an important role in the mineralization of human dental pulp cells (hDPCs).
      A previous study by our group has shown that increased levels of Ca2+ can promote
      hDPC-mediated mineralization in long-term cultures (21 days). However, the
      initiation of mineralization occurs in the early stage of osteogenic inductive
      culture, and the effects of Ca2+ on the mineralization of hDPCs in short-term
      cultures (five days) have not been studied in detail. Furthermore, the underlying
      mechanism by which Ca2+ stimulates the mineralization of hDPCs has remained
      controversial. A strong correlation between mineralization and cell apoptosis
      and/or death has been identified. Thus, the present study hypothesized that Ca2+
      may promote the onset of hDPC-mediated mineralization through inducing their
      apoptosis and/or death. To verify this hypothesis, Ca2+ was added to the growth
      culture medium and osteogenic culture medium at various concentrations. Alizarin
      Red S staining and reverse transcription-polymerase chain reaction analysis were
      used to evaluate the onset of mineralization. Furthermore, the cell counting kit
      8 and fluorescein isothiocyanate-Annexin V/propidium iodide double-staining
      method were adopted to detect the proliferation and apoptosis of hDPCs in the
      growth culture medium. An animal experiment and scanning electron microscopic
      observation of ceramic graft implants were applied to measure the mineralization
      in vivo. The results showed that 5.4 and 9.0 mM Ca2+ accelerated the onset of
      mineralized matrix nodule formation, promoted osteopontin mRNA expression and
      induced marked cell apoptosis and necrosis, but had no obvious effect on cell
      proliferation. These findings indicated a positive association between cell
      apoptosis and/or death and the timing of formation as well as the quantity of
      extracellular mineralization induced by Ca2+ in short-term cultured hDPCs.

PMID- 25999213
TI  - Expression of KRAS in the endometrium of early pregnant mice and its effect
      during embryo implantation.
AB  - This study investigated the expression pattern of Ki-ras2 Kirsten rat sarcoma
      viral oncogene homolog (KRAS) in the endometrium of early-stage pregnant mice and
      its function during embryo implantation. The expression of KRAS was measured at
      the mRNA level using real-time polymerase chain reaction (PCR) and at the protein
      level using immunohistochemistry and western blotting. The expressions of KRAS
      mRNA and protein were not significantly different in the endometrium of
      pseudopregnant and early-stage pregnant mice. However, the immunohistochemistry
      results showed that KRAS was highly expressed in the decidualizing stromal cells
      on days 5-7 of mouse pregnancy and was enhanced in the epithelial cells as
      pregnancy progressed. The expression of KRAS protein was higher after the stromal
      cell was artificially decidualized in vivo and in vitro. Stromal cell
      proliferation was attenuated after down-regulating KRAS expression. After
      silencing KRAS in the mouse uterus, the embryo implantation rate was
      significantly reduced (P < 0.005). We speculate that KRAS may regulate the
      stromal cell proliferation and differentiation progress and then affect the
      embryo implantation process. This study reveals that KRAS plays an important role
      in regulating the embryo implantation process. 

PMID- 25999212
TI  - Associations of Coffee Drinking with Systemic Immune and Inflammatory Markers.
AB  - BACKGROUND: Coffee drinking has been inversely associated with mortality as well
      as cancers of the endometrium, colon, skin, prostate, and liver. Improved insulin
      sensitivity and reduced inflammation are among the hypothesized mechanisms by
      which coffee drinking may affect cancer risk; however, associations between
      coffee drinking and systemic levels of immune and inflammatory markers have not
      been well characterized. METHODS: We used Luminex bead-based assays to measure
      serum levels of 77 immune and inflammatory markers in 1,728 older non-Hispanic
      Whites. Usual coffee intake was self-reported using a food frequency
      questionnaire. We used weighted multivariable logistic regression models to
      examine associations between coffee and dichotomized marker levels. We conducted
      statistical trend tests by modeling the median value of each coffee category and
      applied a 20% false discovery rate criterion to P values. RESULTS: Ten of the 77
      markers were nominally associated (P trend < 0.05) with coffee drinking. Five
      markers withstood correction for multiple comparisons and included aspects of the
      host response namely chemotaxis of monocytes/macrophages (IFNgamma,
      CX3CL1/fractalkine, CCL4/MIP-1beta), proinflammatory cytokines (sTNFRII), and
      regulators of cell growth (FGF-2). Heavy coffee drinkers had lower circulating
      levels of IFNgamma [odds ratios (OR), 0.35; 95% confidence intervals (CI), 0.16
      0.75], CX3CL1/fractalkine (OR, 0.25; 95% CI, 0.10-0.64), CCL4/MIP-1beta (OR,
      0.48; 95% CI, 0.24-0.99), FGF-2 (OR, 0.62; 95% CI, 0.28-1.38), and sTNFRII (OR,
      0.34; 95% CI, 0.15-0.79) than non-coffee drinkers. CONCLUSIONS: Lower circulating
      levels of inflammatory markers among coffee drinkers may partially mediate
      previously observed associations of coffee with cancer and other chronic
      diseases. IMPACT: Validation studies, ideally controlled feeding trials, are
      needed to confirm these associations.

PMID- 25999214
TI  - Physical activity, fatness, educational level and snuff consumption as
      determinants of semen quality: findings of the ActiART study.
AB  - In this study, the association between physical activity and other potential
      determinants, objectively measured by accelerometry, was examined. Sixty-two men
      attending an infertility clinic participated in the study. Obese men (body mass
      index >= 30) and those with a waist circumference 102 cm or more had lower semen
      volume than the other men (P < 0.05). Higher values in sperm parameters were
      observed in participants who completed university studies and those who did not
      consume snuff, compared with the other participants (P < 0.05). Finally, men who
      spent an average number of 10 min-bouts of moderate-to-vigorous physical activity
      had significantly better semen quality than those who engaged in low or high
      numbers of bouts of activity (P < 0.05). No associations were found for sedentary
      or moderate-to-vigorous physical activity time when it was not sustained over 10
      min, i.e. not in bouts. Men who have average levels of physical activity over
      sustained periods of 10 min are likely to have better semen quality than men who
      engage in low or high levels of such activity. Similarly, high levels of total
      and central adiposity, low educational level and snuff consumption are negatively
      related to semen quality. 

PMID- 25999215
TI  - Ligand control in the photochemical generation of high-valent porphyrin-iron-oxo
      derivatives.
AB  - Visible-light irradiation of photo-labile bromate porphyrin-iron(III) salts gave
      iron(IV)-oxo porphyrin radical cations (compound I model) or the neutral iron(IV)
      oxo porphyrin (compound II model), depending on the electronic structure of
      porphyrin ligands.

PMID- 25999216
TI  - Comparative analysis of microsatellites in chloroplast genomes of lower and
      higher plants.
AB  - Microsatellites, or simple sequence repeats (SSRs), contain repetitive DNA
      sequence where tandem repeats of one to six base pairs are present number of
      times. Chloroplast genome sequences have been  shown to possess extensive
      variations in the length, number and distribution of SSRs. However, a comparative
      analysis of chloroplast microsatellites is not available. Considering their
      potential importance in generating genomic diversity, we have systematically
      analysed the abundance and distribution of simple and compound microsatellites in
      164 sequenced chloroplast genomes from wide range of plants. The key findings of
      these studies are (1) a large number of mononucleotide repeats as compared to
      SSR(2-6)(di-, tri-, tetra-, penta-, hexanucleotide repeats) are present in all
      chloroplast genomes investigated, (2) lower plants such as algae show wide
      variation in relative abundance, density and distribution of microsatellite
      repeats as compared to flowering plants, (3) longer SSRs are excluded from coding
      regions of most chloroplast genomes, (4) GC content has a weak influence on
      number, relative abundance and relative density of mononucleotide as well as
      SSR(2-6). However, GC content strongly showed negative correlation with relative
      density (R (2) = 0.5, P < 0.05) and relative abundance (R (2) = 0.6, P < 0.05) of
      cSSRs. In summary, our comparative studies of chloroplast genomes illustrate the
      variable distribution of microsatellites and revealed that chloroplast genome of
      smaller plants possesses relatively more genomic diversity compared to higher
      plants. 

PMID- 25999218
TI  - 50 years of levodopa.

PMID- 25999219
TI  - Epidemiology of Lyme disease.
AB  - Lyme disease is the most common vector-borne illness in North America and Europe.
      The etiologic agent, Borrelia burgdorferi sensu lato, is transmitted to humans by
      certain species of Ixodes ticks, which are found widely in temperate regions of
      the Northern hemisphere. Clinical features are diverse, but death is rare. The
      risk of human infection is determined by the geographic distribution of vector
      tick species, ecologic factors that influence tick infection rates, and human
      behaviors that promote tick bite. Rates of infection are highest among children 5
      to 15 years old and adults older than 50 years.

PMID- 25999217
TI  - Cell signaling and transcription factors regulating cell fate during formation of
      the mouse blastocyst.
AB  - The first cell fate decisions during mammalian development establish tissues
      essential for healthy pregnancy. The mouse has served as a valuable model for
      discovering pathways regulating the first cell fate decisions because of the ease
      with which early embryos can be recovered and the availability of an arsenal of
      classical and emerging methods for manipulating gene expression. We summarize the
      major pathways that govern the first cell fate decisions in mouse development.
      This knowledge serves as a paradigm for exploring how emergent properties of a
      self-organizing system can dynamically regulate gene expression and cell fate
      plasticity. Moreover, it brings to light the processes that establish healthy
      pregnancy and ES cells. We also describe unsolved mysteries and new technologies
      that could help to overcome experimental challenges in the field. 

PMID- 25999220
TI  - Erythema migrans.
AB  - Erythema migrans (EM) is the most common objective manifestation of Borrelia
      burgdorferi infection. Systemic symptoms are usually present. Most patients do
      not recall a preceding tick bite. Despite a characteristic appearance, EM is not
      pathognomonic for Lyme disease and must be distinguished from other similar
      appearing skin lesions. EM is a clinical diagnosis; serologic and PCR assays are
      unnecessary. Leukopenia and thrombocytopenia are indicative of either an
      alternative diagnosis, or coinfection with another tick-borne pathogen. When EM
      is promptly treated with appropriate antimicrobial agents, the prognosis is
      excellent. Persons in endemic areas should take measures to prevent tick bites. 

PMID- 25999221
TI  - Nervous system Lyme disease.
AB  - Lymphocytic meningitis, cranial neuritis or radiculoneuritis occur in up to 15%
      of patients with untreated Borrelia burgdorferi infection. Presentations of
      multifocal PNS involvement can range from painful monoradiculitis to confluent
      mononeuropathy multiplex. Serologic testing is highly accurate after 4 to 6 weeks
      of infection. In CNS infection, production of anti-Bburgdorferi antibody is often
      demonstrable in CSF. Oral antimicrobials are microbiologically curative in
      virtually all patients, including acute European neuroborreliosis. Severe cases
      may require parenteral treatment. The fatigue and cognitive symptoms seen in some
      patients with extra-neurological disease are neither evidence of CNS infection
      nor specific to Lyme disease. 

PMID- 25999222
TI  - Lyme carditis.
AB  - Lyme disease is a common disease that uncommonly affects the heart. Because of
      the rarity of this diagnosis and the frequent absence of other concurrent
      clinical manifestations of early Lyme disease, consideration of Lyme carditis
      demands a high level of suspicion when patients in endemic areas come to
      attention with cardiovascular symptoms and evidence of higher-order heart block.
      A majority of cases manifest as atrioventricular block. A minority of Lyme
      carditis cases are associated with myopericarditis. Like other manifestations of
      Lyme disease, carditis can readily be managed with antibiotic therapy and
      supportive care measures, such that affected patients almost always completely
      recover. 

PMID- 25999223
TI  - Diagnosis and treatment of Lyme arthritis.
AB  - In the United States, Lyme arthritis is the most common feature of late-stage
      Borrelia burgdorferi infection, usually beginning months after the initial bite.
      In some, earlier phases are asymptomatic and arthritis is the presenting
      manifestation. Patients with Lyme arthritis have intermittent or persistent
      attacks of joint swelling and pain in 1 or a few large joints. Serologic testing
      is the mainstay of diagnosis. Synovial fluid polymerase chain reaction for B
      burgdorferi DNA is often positive before treatment, but is not a reliable marker
      of spirochetal eradication after therapy. This article reviews the clinical
      manifestations, diagnosis, and management of Lyme arthritis. 

PMID- 25999224
TI  - Lyme disease in children.
AB  - The diagnosis and management of Lyme disease in children is similar to that in
      adults with a few clinically relevant exceptions. The use of doxycycline as an
      initial empiric choice is to be avoided for children 8 years old and younger.
      Children may present with insidious onset of elevated intracranial pressure
      during acute disseminated Lyme disease; prompt diagnosis and treatment of this
      condition is important to prevent loss of vision. Children who acquire Lyme
      disease have an excellent prognosis even when they present with the late
      disseminated manifestation of Lyme arthritis. Guidance on the judicious use of
      serologic tests is provided. Pediatricians and family practitioners should be
      familiar with the prevention and management of tick bites, which are common in
      children.

PMID- 25999226
TI  - Posttreatment Lyme disease syndrome.
AB  - The prognosis following appropriate antibiotic treatment of early or late Lyme
      disease is favorable but can be complicated by persistent symptoms of unknown
      cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by
      fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months
      or longer after completion of antibiotic therapy. Risk factors include delayed
      diagnosis, increased severity of symptoms, and presence of neurologic symptoms at
      time of initial treatment. Two-tier serologic testing is neither sensitive nor
      specific for diagnosis of PTLDS because of variability in convalescent serologic
      responses after treatment of early Lyme disease. Optimal treatment of PTLDS
      awaits more precise understanding of the pathophysiologic mechanisms involved in
      this illness and future treatment trials.

PMID- 25999225
TI  - Laboratory diagnosis of Lyme disease: advances and challenges.
AB  - The majority of laboratory tests performed for the diagnosis of Lyme disease are
      based on detection of the antibody responses against B burgdorferi in serum. The
      sensitivity of antibody-based tests increases with the duration of the infection.
      Patients early in their illness are more likely to have a negative result. There
      is a need to simplify the testing algorithm for Lyme disease, improving
      sensitivity in early disease while still maintaining high specificity and
      providing information about the stage of infection. The development of a point of
      care assay and biomarkers for active infection would be major advances for the
      field. 

PMID- 25999227
TI  - Chronic Lyme disease.
AB  - Chronic Lyme disease is a poorly defined diagnosis that is usually given to
      patients with prolonged, unexplained symptoms or with alternative medical
      diagnoses. Data do not support the proposition that chronic, treatment-refractory
      infection with Borrelia burgdorferi is responsible for the many conditions that
      get labeled as chronic Lyme disease. Prolonged symptoms after successful
      treatment of Lyme disease are uncommon, but in rare cases may be severe.
      Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms
      and are associated with considerable harm. 

PMID- 25999228
TI  - Human granulocytic anaplasmosis.
AB  - Human granulocytic anaplasmosis, a deer tick-transmitted rickettsial infection
      caused by Anaplasma phagocytophilum, is a common cause of undifferentiated fever
      in the northeast and upper Midwest United States. Patients are often initially
      diagnosed with a mild viral infection, and illness readily resolves in most
      cases. However, as many as 3% develop life-threatening complications and nearly
      1% die from the infection. Although coinfections with Borrelia burgdorferi and
      Babesia microti occur, there is little evidence to suggest synergism of disease
      or a role for A phagocytophilum in chronic illness. No vaccine is available. 

PMID- 25999230
TI  - Update and Commentary on Four Emerging Tick-Borne Infections: Ehrlichia muris
      like Agent, Borrelia miyamotoi, Deer Tick Virus, Heartland Virus, and Whether
      Ticks Play a Role in Transmission of Bartonella henselae.
AB  - Emerging tick-borne infections continue to be observed in the United States and
      elsewhere. Current information on the epidemiology, clinical and laboratory
      features, and treatment of infections due to Ehrlichia muris-like agent, deer
      tick virus, Borrelia miyamotoi sensu lato, and Heartland virus was provided and
      critically reviewed. More research is needed to define the incidence and to
      understand the clinical and the laboratory features of these infections. There is
      also a growing need for the development of sensitive and specific serologic and
      molecular assays for these infections that are easily accessible to clinicians.

PMID- 25999229
TI  - Babesiosis.
AB  - Babesiosis is caused by intraerythrocytic protozoan parasites that are
      transmitted by ticks, or less commonly through blood transfusion or
      transplacentally. Human babesiosis was first recognized in a splenectomized
      patient in Europe but most cases have been reported from the northeastern and
      upper midwestern United States in people with an intact spleen and no history of
      immune impairment. Cases are reported in Asia, Africa, Australia, Europe, and
      South America. Babesiosis shares many clinical features with malaria and can be
      fatal, particularly in the elderly and the immunocompromised. 

PMID- 25999231
TI  - Lyme disease: knowing good evidence to help inform practice.

PMID- 25999232
TI  - Investigations on the catalytic carboxylation of olefins with CO2 towards
      alpha,beta-unsaturated carboxylic acid salts: characterization of intermediates
      and ligands as well as substrate effects.
AB  - The carboxylation of olefins beyond ethylene towards alpha,beta-unsaturated
      carboxylic acid salts and a detailed investigation on the critical steps in the
      catalysis are reported. The influence of two chelating phosphine ligands and
      several olefins on the elemental steps of the catalysis is shown. The work
      focusses on the formation of intermediate olefin complexes, lactone formation and
      base induced elimination of the lactone. The direct carboxylation of olefins is
      possible using nickel catalysts, which opens a new route towards the desired
      alpha,beta-unsaturated carboxylic acid salts. The reaction works particularly
      well for 1,3-dienes and proceeds via the formation of allyl-carboxylates. The
      ability to form such allyl-type lactone complexes seems in this case to be the
      most challenging step towards satisfactory turnover numbers. 

PMID- 25999233
TI  - Reference values and universal screening of thyroid function in the first
      trimester of the population of pregnant women in Toledo (Spain).

PMID- 25999235
TI  - Microemulsion versus emulsion as effective carrier of hydroxytyrosol.
AB  - Two edible Water-in-Oil (W/O) dispersions, an emulsion that remains kinetically
      stable and a microemulsion which is spontaneously formed, transparent and
      thermodynamically stable, were developed for potential use as functional foods,
      due to their ability to be considered as matrices to encapsulate biologically
      active hydrophilic molecules. Both systems contained Medium Chain Triglycerides
      (MCT) as the continuous phase and were used as carriers of Hydroxytyrosol (HT), a
      hydrophilic antioxidant of olive oil. A low energy input fabrication process of
      the emulsion was implemented. The obtained emulsion contained 1.3% (w/w) of
      surfactants and 5% (w/w) aqueous phase. The spontaneously formed microemulsion
      contained 4.9% (w/w) of surfactants and 2% (w/w) aqueous phase. A comparative
      study in terms of structural characterization of the systems in the absence and
      presence of HT was carried out. Particle size distribution obtained by Dynamic
      Light Scattering (DLS) technique and interfacial properties of the surfactants'
      layer, examined by Electron Paramagnetic Resonance (EPR) spectroscopy indicated
      the involvement of HT in the surfactant membrane. Finally, the proposed systems
      were studied for the scavenging activity of the encapsulated antioxidant toward
      galvinoxyl stable free radical showing a high scavenging activity of HT in both
      systems. 

PMID- 25999236
TI  - Reproducibility of mRECIST in assessing response to transarterial
      radioembolization therapy in hepatocellular carcinoma.
AB  - The purpose of our study was to evaluate the reproducibility of Modified Response
      Evaluation Criteria in Solid Tumors (mRECIST) in hepatocellular carcinoma (HCC)
      lesions undergoing transarterial radioembolization (TARE) therapy and to
      determine whether mRECIST reproducibility is affected by the enhancement pattern
      of HCC. One hundred and three HCC lesions from 103 patients treated with TARE
      were evaluated. The single longest diameter of viable tumor tissue was measured
      by two radiologists at baseline; response to therapy was evaluated according to
      mRECIST. The enhancement pattern of HCC lesions was correlated with their mRECIST
      response. The response rate between mRECIST and RECIST 1.1 was compared. Wilcoxon
      signed-rank test, paired t test, Lin's concordance correlation coefficient (rhoc
      ), Bland-Altman plot, kappa statistics, and Fisher's exact test were used to
      assess intra- and interobserver reproducibilities and to compare response rates.
      There were better intra- than interobserver agreements in the measurement of
      single longest diameter of viable tumor tissue (bias = 0 cm intraobserver versus
      bias = 0.3 cm interobserver). For mRECIST, good intraobserver (K = 0.70) and
      moderate interobserver (K = 0.56) agreements were noted. The mRECIST response for
      HCC lesions with homogeneous enhancement at both baseline and follow-up imaging
      showed better intra- and interobserver agreements (K = 0.77 and 0.60,
      respectively) than lesions with heterogeneous enhancement at both scans (K = 0.54
      and 0.40, respectively). In the early follow-up period mRECIST showed a
      significantly higher response rate than RECIST (40.8% versus 3.9%; P = 0.025).
      CONCLUSIONS: In HCC patients treated with TARE, mRECIST captures a significantly
      higher response rate compared with RECIST; it also demonstrates acceptable intra-
      and interobserver reproducibilities for HCC lesions treated with TARE, and
      mRECIST reproducibility may be lower for HCC lesions with heterogeneous
      distribution of the viable tumor tissue.

PMID- 25999234
TI  - Tools and resources for analyzing gene expression changes in glaucomatous
      neurodegeneration.
AB  - Evaluating gene expression changes presents one of the most powerful
      interrogative approaches to study the molecular, biochemical, and cellular
      pathways associated with glaucomatous disease pathology. Technologies to study
      gene expression profiles in glaucoma are wide ranging. Qualitative techniques
      provide the power of localizing expression changes to individual cells, but are
      not robust to evaluate differences in expression changes. Alternatively,
      quantitative changes provide a high level of stringency to quantify changes in
      gene expression. Additionally, advances in high throughput analysis and
      bioinformatics have dramatically improved the number of individual genes that can
      be evaluated in a single experiment, while dramatically reducing amounts of input
      tissue/starting material. Together, gene expression profiling and proteomics have
      yielded new insights on the roles of neuroinflammation, the complement cascade,
      and metabolic shutdown as important players in the pathology of the optic nerve
      head and retina in this disease. 

PMID- 25999237
TI  - MAPK-mediated enhanced expression of vacuolar H(+)-ATPase confers the improved
      adaption to NaCl stress in a halotolerate peppermint (Mentha piperita L.).
AB  - Vacuolar H(+)-ATPase (V-H(+)-ATPase) has been proved to be of importance in
      maintenance of ion homeostasis inside plant cells under NaCl stress. In this
      study, the expression levels and salt-tolerate function of V-H(+)-ATPase genes
      were investigated in the roots and leaves of a halotolerate peppermint (Mentha *
      piperita L.) Keyuan-1 treated with different concentrations of NaCl. Results
      showed that the expressions of V-H(+)-ATPase in the transcriptional, protein and
      activity levels were significantly enhanced in the halotolerate peppermint Keyuan
      1 compared to the wild-type (WT) peppermint under 50, 100, and 150 mM NaCl
      treatment. Moreover, inhibition experiments exhibited that V-H(+)-ATPase activity
      played vital roles in the salt tolerance of peppermint Keyuan-1 to 150 mM NaCl
      stress through increasing the vacuolar H(+) pumping activity and Na(+)
      compartmentalization capacity. Furthermore, results of Western blots showed that
      the activity of a mitogen-activated protein kinase (MAPK) was significantly
      increased under different concentrations of NaCl in the halotolerate peppermint
      Keyuan-1, which was much higher than that of WT peppermint. Further experiments
      with inhibitors suggested that this MAPK protein was responsible for the enhanced
      expression of V-H(+)-ATPase in the halotolerate peppermint Keyuan-1. In response
      to NaCl stress, increase of cytoplasmic calcium concentration ([Ca(2+)]cyt)
      occurred upstream of MAPK activation in the halotolerate peppermint Keyuan-1. In
      all, these findings demonstrated that increased V-H(+)-ATPase activity was
      positively correlated with the enhanced salt tolerance in the halotolerate
      peppermint Keyuan-1, providing the theoretic basis for the further development
      and utilization of peppermint in saline areas.

PMID- 25999238
TI  - Downscaling the Sample Thickness to Sub-Micrometers by Employing Organic
      Photovoltaic Materials as a Charge-Generation Layer in the Time-of-Flight
      Measurement.
AB  - Time-of-flight (TOF) measurements typically require a sample thickness of several
      micrometers for determining the carrier mobility, thus rendering the
      applicability inefficient and unreliable because the sample thicknesses are
      orders of magnitude higher than those in real optoelectronic devices. Here, we
      use subphthalocyanine (SubPc):C70 as a charge-generation layer (CGL) in the TOF
      measurement and a commonly hole-transporting layer, N,N'-diphenyl-N,N'-bis(1,1'
      biphenyl)-4,4'-diamine (NPB), as a standard material under test. When the NPB
      thickness is reduced from 2 to 0.3 MUm and with a thin 10-nm CGL, the hole
      transient signal still shows non-dispersive properties under various applied
      fields, and thus the hole mobility is determined accordingly. Only 1-MUm NPB is
      required for determining the electron mobility by using the proposed CGL. Both
      the thicknesses are the thinnest value reported to data. In addition, the
      flexibility of fabrication process of small molecules can deposit the proposed
      CGL underneath and atop the material under test. Therefore, this technique is
      applicable to small-molecule and polymeric materials. We also propose a new
      approach to design the TOF sample using an optical simulation. These results
      strongly demonstrate that the proposed technique is valuable tool in determining
      the carrier mobility and may spur additional research in this field.

PMID- 25999239
TI  - Current status and updated recommendations for diagnosis and treatment of plasma
      cell myeloma in Switzerland.
AB  - The availability of drugs such as thalidomide, bortezomib and lenalidomide
      changed the landscape in myeloma treatment and has extended the median survival
      up to 10 years with a substantial improvement in quality of life. This
      development prompted a Swiss expert panel to re-evaluate the current status and
      formulate updated clinical recommendations for the diagnosis and treatment of
      plasma cell myeloma. These recommendations should help clinicians in their
      decision making to achieve the best outcome based on currently available data. 

PMID- 25999240
TI  - Tracing the footprints of the breast cancer oncogene BRK - Past till present.
AB  - Twenty years have passed since the non-receptor tyrosine kinase, Breast tumor
      kinase (BRK) was cloned. While BRK is evolutionarily related to the Src family
      kinases it forms its own distinct sub-family referred here to as the BRK family
      kinases. The detection of BRK in over 60% of breast carcinomas two decades ago
      and more remarkably, its absence in the normal mammary gland attributed to its
      recognition as a mammary gland-specific potent oncogene and led BRK researchers
      on a wild chase to characterize the role of the enzyme in breast cancer. Where
      has this chase led us? An increasing number of studies have been focused on
      understanding the cellular roles of BRK in breast carcinoma and normal tissues. A
      majority of such studies have proposed an oncogenic function of BRK in breast
      cancers. Thus far, the vast evidence gathered highlights a regulatory role of BRK
      in critical cellular processes driving tumor formation such as cell
      proliferation, migration and metastasis. Functional characterization of BRK has
      identified several signaling proteins that work in concert with the enzyme to
      sustain such a malignant phenotype. As such targeting the non-receptor tyrosine
      kinase has been proposed as an attractive approach towards therapeutic
      intervention. Yet much remains to be explored about (a) the discrepant expression
      levels of BRK in cancer versus normal conditions, (b) the dependence on the
      enzymatic activity of BRK to promote oncogenesis and (c) an understanding of the
      normal physiological roles of the enzyme. This review outlines the advances made
      towards understanding the cellular and physiological roles of BRK, the mechanisms
      of action of the protein and its therapeutic significance, in the context of
      breast cancer. 

PMID- 25999241
TI  - Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart
      Failure: A Propensity Score-Matched Analysis.
AB  - BACKGROUND: Carperitide (alpha-human A-type natriuretic peptide) has been used
      for more than one-half of all acute heart failure (AHF) patients in Japan.
      However, its clinical effectiveness is not well documented. METHODS: We
      retrospectively identified AHF patients presenting with acute onset or worsening
      of symptoms and admitted to 1 of the 3 participating hospitals. Propensity score
      matched analysis was performed. The primary end point was in-hospital mortality.
      RESULTS: Of all of the AHF patients included in this study, 402 (38.7%) were
      treated with carperitide, and in-hospital mortality rate for the total cohort was
      7.6%. We matched 367 pairs of patients treated with and without carperitide
      according to propensity score. In this matched cohort, treatment with carperitide
      was associated with in-hospital mortality (odds ratio [OR] 2.13, 95% confidence
      interval [CI] 1.17-3.85; P = .013). Potentially more harmful effects were
      observed in elderly patients (OR 2.93, 95% CI 1.54-5.91). CONCLUSIONS:
      Carperitide was significantly associated with increased in-hospital mortality
      rate in AHF patients. Our results strongly suggest the necessity for well
      designed randomized clinical trials of carperitide to determine its clinical
      safety and effectiveness.

PMID- 25999242
TI  - Comparison of asymptomatic and symptomatic rhinovirus infections in university
      students: incidence, species diversity, and viral load.
AB  - Human rhinovirus (HRV) infections are common but poorly characterized in
      university students. Thus, we characterized asymptomatic and symptomatic HRV
      infections by incidence, species diversity, and viral load of 502 university
      students during September and October of 2010 and 2011 from nasal swabs and
      electronically submitted symptom questionnaires. We tested all symptomatic
      students and randomly sampled participants who remained asymptomatic (n=25/week,
      over 8 weeks each study year) on a weekly basis by real-time PCR and sequenced
      HRV positives. HRV was identified in 33/400 (8.3%) and 85/92 (92.4%) of the
      asymptomatic and symptomatic students, respectively. We identified a higher than
      previously reported rate of HRV-B in both groups, although the distribution of
      HRV species was similar (P=0.37). Asymptomatic viral load averaged 1.2 log10
      copies/mL lower than symptomatic HRV (P<0.001). In conclusion, asymptomatic HRV
      activity preceded peak symptomatic activity in September and October and was
      associated with lower viral load.

PMID- 25999243
TI  - Swirl Flow Bioreactor coupled with Cu-alginate beads: A system for the
      eradication of Coliform and Escherichia coli from biological effluents.
AB  - It is estimated that approximately 1.1 billion people globally drink unsafe
      water. We previously reported both a novel copper-alginate bead, which quickly
      reduces pathogen loading in waste streams and the incorporation of these beads
      into a novel swirl flow bioreactor (SFB), of low capital and running costs and of
      simple construction from commercially available plumbing pipes and fittings. The
      purpose of the present study was to trial this system for pathogen reduction in
      waste streams from an operating Dewats system in Hinjewadi, Pune, India and in
      both simulated and real waste streams in Seattle, Washington, USA. The trials in
      India, showed a complete inactivation of coliforms in the discharged effluent
      (Mean Log removal Value (MLRV) = 3.51), accompanied by a total inactivation of E.
      coli with a MLRV of 1.95. The secondary clarifier effluent also showed a 4.38
      MLRV in viable coliforms during treatment. However, the system was slightly less
      effective in reducing E. coli viability, with a MLRV of 1.80. The trials in
      Seattle also demonstrated the efficacy of the system in the reduction of viable
      bacteria, with a LRV of 5.67 observed of viable Raoultella terrigena cells
      (100%). 

PMID- 25999244
TI  - Molecular Analysis of the B Microchromosome in Steindachnerina insculpta
      (Characiformes: Curimatidae) by Microdissection.
AB  - B chromosomes are additional elements to standard karyotypes observed in
      different species of fishes, especially in Curimatidae. However, despite studies
      demonstrating the occurrence of Bs, little is known about their origin and
      evolution. To better understand the genomic composition and evolutionary
      processes involving B chromosomes, microdissection of B microchromosomes in
      Steindachnerina insculpta was conducted. Chromosome painting revealed the totally
      hybridized B and markings on A chromosomes both in S. in sculpta and in
      Cyphocharax spilotus, demonstrating a strong homology between these different
      species. In specimens of C. modestus, which do not have Bs, the signals were
      observed on A chromosomes. Cloning and sequencing of some B fragments revealed
      that the B microchromosome in S. insculpta is composed of repetitive elements,
      homologous to the DIRS-4 LTR retrotransposon of Xenopus (Silurana) tropicalis.
      FISH with clone pSi48 with the DIRS-4 retroelement revealed signals on all A
      chromosomes in the 2 species and also on the B, suggesting the insertion of
      repetitive elements in these species. 

PMID- 25999245
TI  - Clinical Presentation and Outcomes of Autoimmune Hepatitis in Inflammatory Bowel
      Disease.
AB  - Nearly one-third of patients with inflammatory bowel disease (IBD) have abnormal
      liver tests, which can be indicative of underlying hepatic disease. Primary
      sclerosing cholangitis has a clear association with ulcerative colitis, but other
      autoimmune disorders such as autoimmune hepatitis (AIH) have also been associated
      with IBD. AIH may also occur in the setting of an overlap syndrome or in the
      setting of medications, particularly tumor necrosis factor alpha inhibitors.
      Importantly, some studies have shown that IBD patients with AIH fail treatment
      more frequently than IBD patients without AIH. This review will focus on the
      clinical characteristics, diagnosis, and management of autoimmune hepatitis in
      inflammatory bowel disease patients. 

PMID- 25999247
TI  - Challenges to the Treatment and New Perspectives for the Eradication of
      Helicobacter pylori.
AB  - Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases
      such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current
      treatment of H. pylori infection with antibiotics and proton pump inhibitors has
      several limitations, including poor adherence and intrinsic patient-related
      factors, drug resistance, and the absence of adequate treatments. This review
      summarizes the current therapeutic approaches to eradicating H. pylori, the
      difficulties associated with its treatment, and several new perspectives aimed at
      improving existing treatment strategies. 

PMID- 25999248
TI  - IL-7: AhR We Ready for a New Cytokine to Fight Colitis?

PMID- 25999249
TI  - Geriatric emergency general surgery: Survival and outcomes in a low-middle income
      country.
AB  - BACKGROUND: Geriatric patients remain largely unstudied in low-middle income
      health care settings. The purpose of this study was to compare the epidemiology
      and outcomes of older versus younger adults with emergency general surgical
      conditions in South Asia. METHODS: Discharge data from March 2009 to April 2014
      were obtained for all adult patients (>=16 years) with an International
      Classification of Diseases, 9th revision, Clinical Modification diagnosis codes
      consistent with an emergency general surgery condition as defined by the American
      Association for the Surgery of Trauma. Multivariable regression analyses compared
      patients >65 years of age with patients <=65 years for differences in all-cause
      mortality, major complications, and duration of hospital stay. Models were
      adjusted for potential confounding owing to patient demographic and clinical case
      mix data with propensity scores. RESULTS: We included 13,893 patients; patients
      >65 years constituted 15% (n = 2,123) of the cohort. Relative to younger
      patients, older adults were more likely to present with a number of emergency
      general surgery conditions, including gastrointestinal bleeding (odds ratio OR
      [95% CI], 2.63[1.99-3.46]), resuscitation (2.17 [1.67-2.80]), and peptic ulcer
      disease (2.09 [1.40-3.10]). They had an 89% greater risk-adjusted odds (1.89
      [1.55-2.29]) of complications and a 63% greater odds (1.63 [1.21-2.20]) of
      mortality. Restricted to patients undergoing operative interventions, older
      adults had 95% greater odds (1.95 [1.29-2.94]) of complications and 117% greater
      odds (2.17 [1.62-2.91]) of mortality. CONCLUSION: Understanding unique needs of
      geriatric patients is critical to enhancing the management and prioritization of
      appropriate care in developing settings.

PMID- 25999250
TI  - Postoperative outcomes with cholecystectomy in lung transplant recipients.
AB  - INTRODUCTION: There is a paucity of data on outcomes for lung transplant (LT)
      recipients requiring general surgery procedures. This study examined outcomes
      after cholecystectomy in LT recipients using a large database. METHODS: The
      National Inpatient Sample Database (2005-2010) was queried for all LT patients
      requiring laparoscopic cholecystectomy (LC) and open cholecystectomy (OC).
      RESULTS: There were a total of 377 cholecystectomies performed in LT patients.
      The majority were done for acute cholecystitis (n = 218; 57%) and were done
      urgently/emergently (n = 258; 68%). There were a total of 304 (81%) laparoscopic
      cholecystectomies and 73 (19%) OC. There was no difference in age when comparing
      the laparoscopic and open groups (53.6 vs 55.5 years; P = .39). In addition, the
      Charlson Comorbidity Index was similar in the 2 groups (P = .07). Patients
      undergoing OC were more likely to have perioperative myocardial infarction,
      pulmonary embolus, or any complication compared with the laparoscopic group.
      Total hospital charges ($59,137.00 vs $106,329.80; P = .03) and median duration
      of stay (4.0 vs 8.0 days; P = .02) were both greater with open compared with LC.
      CONCLUSION: Cholecystectomy can be performed safely in the LT population with
      minimal morbidity and mortality.

PMID- 25999251
TI  - Net health benefit of hepatic resection versus intraarterial therapies for
      neuroendocrine liver metastases: A Markov decision model.
AB  - BACKGROUND: Management of patients with neuroendocrine liver metastasis (NELM)
      remains controversial. We sought to compare the net health benefit (NHB) of
      hepatic resection (HR) versus intraarterial therapy (IAT) among patients with
      NELM. METHODS: A decision analytic Markov model was created to estimate and
      compare the cost effectiveness associated with different management strategies
      (HR vs IAT) for a simulated cohort of patients with NELM. The primary (base case)
      analysis was calculated based on a 57-year-old male patient with metachronous,
      symptomatic NELM that involved <25% of the liver in the absence of extrahepatic
      disease. The endpoints were quality-adjusted life-months (QALMs), quality
      adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and NHB.
      RESULTS: In the base case analysis, HR was strongly favored over IAT providing
      NHB of 20.0 QALMs and an ICER of $8,427 per QALY. In the Monte Carlo simulation,
      the greatest NHB for HR was among patients with functioning/symptomatic NELM,
      regardless of liver tumor burden. In the symptomatic group, IAT was favored only
      in a minority of old patients (>60 years) with extrahepatic disease and
      synchronous NELM. In contrast, in patients with nonfunctioning/asymptomatic NELM,
      hepatic tumor burden was the most important variable and HR was always cost
      ineffective in large tumors, independent of patient age and extrahepatic disease
      characteristics. CONCLUSION: A Markov decision model demonstrated that HR was the
      preferred strategy among patients with symptomatic NELM, regardless of hepatic
      disease burden. In contrast, IAT should be preferred for patients with large
      volume nonfunctioning/asymptomatic NELM.

PMID- 25999252
TI  - When is it safe to forgo abdominal CT in blunt-injured children?
AB  - INTRODUCTION: CT is the standard modality to diagnose solid organ injury after
      blunt trauma; however, the associated radiation carries a risk of cancer. We
      hypothesized that there are patient-specific factors that can identify those
      children who require abdominal CT. METHODS: We reviewed all children admitted to
      2 pediatric trauma centers after blunt trauma with liver or spleen injury from
      January 2009 to December 2013. The low-risk group was defined as a Glasgow Coma
      Scale (GCS) of 15 with normal pediatric age-adjusted shock index (heart
      rate/systolic blood pressure; SIPA) on presentation, and injury attributable to a
      single, nonmotorized, blunt force to the abdomen. The at-risk group did not meet
      these criteria. RESULTS: We identified 206 children with blunt liver or spleen
      injury, 101 of whom met the low-risk criteria. Among these 101 children who met
      the low-risk criteria, there were no deaths, no children required laparotomy,
      only 1 child required a packed red cell transfusion, and no children required
      discharge to a rehabilitation facility. CONCLUSION: Children who present to the
      emergency department after blunt abdominal trauma by a nonmotorized force with a
      normal GCS and SIPA are unlikely to have a solid organ injury that will require
      intervention.

PMID- 25999253
TI  - The effect of surgical approach on short-term oncologic outcomes in rectal cancer
      surgery.
AB  - BACKGROUND: Although evidence to support the use of laparoscopic and robotic
      approaches for the treatment of rectal cancer is limited, these approaches are
      being adopted broadly. We sought to investigate national practice patterns and
      compare short-term oncologic outcomes of different approaches for rectal cancer
      resections. METHODS: The 2010 National Cancer Database was queried for operative
      cases of rectal cancer. Approach was classified as open, laparoscopic, or
      robotic. Patient, tumor, and hospital characteristics and surgical margin status
      were evaluated. Propensity score matching was used to compare outcomes across
      approaches. RESULTS: We identified 8,712 patients. Laparoscopic and robotic
      approaches were more common in privately insured and wealthier patients at high
      volume centers (P < .001). Open approaches were used for tumors with higher
      histologic grade and pathologic stage (P < .001). A minimally invasive approach
      was associated with fewer positive margins and shorter hospital stays. After
      propensity score matching, the laparoscopic approach was associated with a 2.0%
      lesser (P = .01) and robotic surgery with a 3.8% lesser (P = .004) incidence of
      positive margins compared with open surgery. CONCLUSION: An open approach is
      often used in rectal cancers with higher pathologic stages. Matched patient
      analysis suggests minimally invasive approaches are associated with improved R0
      resections.

PMID- 25999246
TI  - Transitioning from Idiopathic to Explainable Autoimmune Hepatitis.
AB  - Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the
      exclusion of etiologically defined diseases that resemble it. Insights into its
      pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable
      disease, and the goal of this review is to describe the insights that are
      hastening this transition. Two types of autoimmune hepatitis are justified by
      serological markers, but they also have distinctive genetic associations (DRB1
      and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility
      factors in white adults, and a six amino acid sequence encoded in the antigen
      binding groove of class II molecules of the major histocompatibility complex can
      influence the selection of autoantigens. Polymorphisms, including variants of
      SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The
      cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2
      autoimmune hepatitis, and it shares homologies with multiple viruses that might
      promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and
      CXCL10, orchestrate the migration of effector cells to sites of injury and are
      associated with disease severity. Cells of the innate and adaptive immune
      responses promote tissue damage, and possible deficiencies in the number and
      function of regulatory T cells may facilitate the injurious process. Receptor
      mediated apoptosis is the principal mechanism of hepatocyte loss, and cell
      mediated and antibody-dependent mechanisms of cytotoxicity also contribute.
      Insights that explain autoimmune hepatitis will allow triggering exogenous
      antigens to be characterized, risk management to be improved, prognostic indices
      to be refined, and site-specific therapeutic interventions to emerge. 

PMID- 25999254
TI  - CD4(+) lymphocytes improve venous blood flow in experimental arteriovenous
      fistulae.
AB  - BACKGROUND: The role of immune cells in arteriovenous fistulae (AVF) maturation
      is poorly understood and has received, until quite recently, little attention.
      This study examines the function of T lymphocytes in AVF vascular remodeling.
      METHODS: Experimental fistulae were created in athymic rnu nude rats lacking
      mature T lymphocytes and euthymic control animals by anastomosing the left
      superior epigastric vein to the nearby femoral artery. Blood flow rates, wall
      morphology, and histologic changes were assessed in AVF 21 days after creation.
      The effect of CD4(+) lymphocytes on AVF maturation in athymic animals was
      analyzed by adoptive transfer of cells after fistula creation. RESULTS: The
      absence of T lymphocytes compromised blood flow in experimental fistulae.
      Histopathologic inspection of AVF from athymic rats revealed that T-cell
      immunodeficiency negatively affected venous vascular remodeling, as evidenced by
      a reduced lumen, a thick muscular layer, and a low number of inflammatory cells
      compared with control animals. Adoptive transfer of CD4(+) lymphocytes from
      euthymic rats into athymic animals after fistula creation improved blood flow and
      reduced intima-media thickness. CONCLUSION: These results point at the protective
      role of CD4(+) lymphocytes in the remodeling of the AVF vascular wall.

PMID- 25999255
TI  - Effectiveness of interventions to improve patient handover in surgery: A
      systematic review.
AB  - BACKGROUND: Handover of patient care is a critical process in the transfer of
      information between clinical teams and clinicians during transitions in patient
      care. The handover process may take many forms and is often unstructured and
      unstandardized, potentially resulting in error and the potential for patient
      harm. The Joint Commission has implicated such errors in up to 80% of sentinel
      events and has published guidelines (using an acronym termed SHARE) for the
      development of intervention tools for handover. This study aims to review
      interventions to improve handovers in surgery and to assess compliance of
      described methodologies with the guidelines of the Joint Commission for design
      and implementation of handover improvement tools. METHODS: A systematic review
      was conducted in line with MOOSE guidelines. Electronic databases Medline,
      EMBASE, and PsyInfo were searched and interventions to improve surgical handover
      identified. Intervention types, development methods, and outcomes were compared
      between studies and assessed against SHARE criteria. RESULTS: Nineteen studies
      were included. These studies included paper and computerized checklists,
      proformas, and/or standardized operating protocols for handover. All reported
      some degree of improvement in handover. Description of development methods, staff
      training, and follow-up outcome data was poor. Only a single study was able to
      demonstrate compliance with all 5 domains guidelines of the of Joint Commission.
      CONCLUSION: Improvements in information transfer may be achieved through
      checklist- or proforma-based interventions in surgical handover. Although initial
      data appear promising, future research must be backed by robust study design,
      relevant outcomes, and clinical implementation strategies to identify the most
      effective means to improve information transfer and optimize patient outcomes.

PMID- 25999256
TI  - Styrene maleic acid copolymer-pirarubicin induces tumor-selective oxidative
      stress and decreases tumor hypoxia as possible treatment of colorectal cancer
      liver metastases.
AB  - BACKGROUND: Pirarubicin, a derivative of doxorubicin, induces tumor destruction
      via the production of reactive oxygen species (ROS) but is associated with
      cardiotoxicity. As a macromolecule (conjugated to styrene-maleic acid [SMA]), SMA
      pirarubicin is selective to tumors resulting in improved survival with decreased
      systemic toxicity. Tumor destruction is, however incomplete, and resistant cells
      at the periphery of the tumor contribute to recurrence. Tumor hypoxia is a major
      factor in tumor resistance. Understanding the effect of oxidative stress induced
      by SMA-pirarubicin on the tumor microenvironment may be key to overcoming
      resistance. This study investigated the pattern of ROS production and tumor
      hypoxia after treatment with SMA-pirarubicin in a murine model of colorectal
      liver metastases. METHODS: Liver metastases were induced in male, CBA mice using
      a murine-derived colon cancer cell line. SMA-pirarubicin (maximum tolerated dose,
      100 mg/kg) or pirarubicin, (maximum tolerated dose, 10 mg/kg) were administered
      intravenously 14 days after tumor induction. Systemic oxidative stress in serum,
      liver, and cardiac tissue was quantified using the thiobarbituric acid reactive
      substances assay. Flow cytometry and fluorescence microscopy were used to assess
      ROS production for 48 hours after treatment. Tumor hypoxia was quantified using
      immunohistochemistry for pimonidazole adducts. RESULTS: SMA-pirarubicin (100
      mg/kg) induced ROS exclusively in tumors with minimal levels in serum and cardiac
      tissue. ROS levels were induced in a time-dependent and dose-dependent manner
      optimal between 4 and 24 hours after drug administration. Although tumor hypoxia
      was decreased overall, residual tumor cells adjacent to patent vessels were
      hypoxic. CONCLUSION: This study provides insight into the tumor microenvironment
      after chemotherapy. SMA-pirarubicin inhibits the growth of colorectal liver
      metastases by inducing ROS, which seems to be largely tumor selective. The
      temporal pattern of ROS production can be used to improve future dosing regimens.
      Furthermore, the observation that residual tumor cells are hypoxic clarifies the
      need for a multimodal approach with agents that can alter the hypoxic state to
      effect complete tumor destruction.

PMID- 25999257
TI  - The relationship between intraoperative teamwork and management skills in patient
      care.
AB  - BACKGROUND: Optimal team performance in the operating room (OR) requires a
      combination of interactions among OR professionals and adherence to clinical
      guidelines. Theoretically, it is possible that OR teams could communicate very
      well but fail to follow acceptable standards of patient care and vice versa. OR
      simulations offer an ideal research environment to study this relationship. The
      goal of this study was to determine the relationship between ratings of OR
      teamwork and communication with adherence to patient care guidelines in a
      simulated scenarios of malignant hyperthermia (MH). METHODS: An interprofessional
      research team (2 anesthesiologists, 1 surgeon, an OR nurse, and a social
      scientist) reviewed videos of 5 intraoperative teams managing a simulated patient
      who manifested MH while undergoing general anesthesia for an epigastric
      herniorraphy in a high-fidelity, in situ OR. Participant teams consisted of 2
      residents from anesthesiology, 1 from surgery, 1 OR nurse, and 1 certified
      surgical technician. Teamwork and communication were assessed with 4 published
      tools: Anesthesiologists' Non-Technical Skills (ANTS), Scrub Practitioners List
      of Intra-operative Non-Technical Skills (SPLINTS), Non-Technical Skills for
      Surgeons (NOTSS), and Objective Teamwork Assessment System (OTAS). We developed
      an evidence-based MH checklist to assess overall patient care. RESULTS:
      Interrater agreement for teamwork tools was moderate. Average rater agreement was
      0.51 For ANTS, 0.67 for SPLINTS, 0.51 for NOTSS, and 0.70 for OTAS. Observer
      agreement for the MH checklist was high (0.88). Correlations between teamwork and
      MH checklist were not significant. Teams were different in percent of the MH
      actions taken (range, 50-91%; P = .006). CONCLUSION: In this pilot study,
      intraoperative teamwork and communication were not related to overall patient
      care management. Separating nontechnical and technical skills when teaching OR
      teamwork is artificial and may even be damaging, because such an approach could
      produce teams with excellent communication skills as they unsuccessfully manage
      the patient. OR simulations offer a unique opportunity to research how to best
      integrate both of these domains to improve patient care.

PMID- 25999258
TI  - Capillary electrophoresis coupled to contactless conductivity detection for the
      analysis of S-nitrosothiols decomposition and reactivity.
AB  - S-Nitrosothiols (RSNO) are composed of a NO group bound to the sulfhydryl group
      of a peptide or protein. RSNO are very important biological molecules, since they
      have many effects on human health. RSNO are easily naturally decomposed by metal
      ions, light, and heat, with different kinetics. They can furthermore undergo
      transnitrosation (NO moieties exchange), which is a crucial point in
      physiological conditions since the concentration ratios between the different
      nitrosothiols is a key factor in many physiopathological processes. There is
      therefore a great need for their quantitation. Many S-nitrosothiol detection and
      quantitation methods need their previous decomposition, leading thus to some
      limitations. We propose a direct quantitation method employing the coupling of
      capillary electrophoresis with a homemade capacitively coupled contactless
      conductivity (C(4) D) detector in order to separate and quantify S
      nitrosoglutathione and its decomposition products. After optimization of the
      method, we have studied the kinetics of decomposition using light and heat. Our
      results show that the decomposition by light is first order (kobs   =  (3.40 +/-
      0.15) * 10(-3)  s(-1) ) while that using heat (at 80 degrees C) is zeroth order
      (kobs,80 degrees C   =  (4.34 +/- 0.14) * 10(-6)  mol L(-1) s(-1) ).
      Transnitrosation reaction between S-nitrosoglutathione and cysteine was also
      studied, showing the possibility of separation and detection of all the products
      of this reaction in less than 2.5 min. 

PMID- 25999259
TI  - Human chorionic gonadotropin stimulates spheroid attachment on fallopian tube
      epithelial cells through the mitogen-activated protein kinase pathway and down
      regulation of olfactomedin-1.
AB  - OBJECTIVE: To study the effect of human chorionic gonadotropin (hCG) on
      olfactomedin-1 (Olfm1) expression and spheroid attachment in human fallopian tube
      epithelial cells in vitro. DESIGN: Experimental study. SETTING: Reproductive
      biology laboratory. PATIENT(S): Healthy nonpregnant women. INTERVENTION(S): No
      patient interventions. MAIN OUTCOME MEASURE(S): Luteinizing hormone/chorionic
      gonadotropin receptor (LHCGR) and Olfm1 expression in fallopian tube epithelium
      cell line (OE-E6/E7 cells). OE-E6/E7 cells treated with hCG, U0126 extracellular
      signal-regulated kinase (ERK) inhibitor, or XAV939 Wnt/beta-catenin inhibitor
      were analyzed by Western blotting, real-time polymerase chain reaction, and in
      vitro spheroid attachment assay. RESULT(S): Human chorionic gonadotropin
      increased spheroid attachment on OE-E6/E7 cells through down-regulation of Olfm1
      and activation of Wnt and mitogen-activated protein kinase (MAPK) signaling
      pathways. U0126 down-regulated both MAPK and Wnt/beta-catenin signaling pathways
      and up-regulated Olfm1 expression. XAV939 down-regulated only the Wnt/beta
      catenin signaling pathway but up-regulated Olfm1 expression. CONCLUSION(S): Human
      chorionic gonadotropin activated both ERK and Wnt/beta-catenin signaling pathways
      and enhanced spheroid attachment on fallopian tube epithelial cells through down
      regulation of Olfm1 expression.

PMID- 25999260
TI  - Training in reproductive endocrinology and infertility and assisted reproductive
      technologies: options and worldwide needs.
AB  - Standardized, high-quality training in reproductive endocrinology, infertility,
      and assisted reproductive technologies (REI-ART) faces challenges owing to the
      high-tech nature of ART and the important country-to-country differences in
      clinical practice and regulations overseeing training. Moreover, while the
      training capacity of the classical by-fellowship training platforms is shrinking,
      an increasing demand for REI-ART specialists is coming from emerging countries.
      To meet this expanding need for REI-ART specialists, we propose a novel by
      network model linking a reference training center to satellite practical training
      sites. Simulation should be used more extensively to achieve competency before
      initiating live clinical experience, analogous to the highly effective training
      systems that have been used in aviation for decades. Large ART databases that
      exist because of obligations to report ART activity and results constitute unique
      yet so far untapped sources for developing by-scenario simulation training
      models. Online training materials incorporating these state-of-the-art
      information technology tools could be developed as a means of fulfilling training
      needs worldwide. 

PMID- 25999261
TI  - [Bullous rash around a peritoneal dialysis catheter exit site].
AB  - BACKGROUND: Cutaneous eruption around a peritoneal dialysis (PD) catheter exit
      site is a rare complication. Herein we report a case of bullous eruption; we
      discuss the diagnostic approach and the related therapeutic implications.
      PATIENTS AND METHODS: A 63-year-old man presented a bullous periumbilical
      eruption two months after initiation of PD. Cultures of laboratory samples ruled
      out an infectious origin and systemic corticosteroids initiated at 0.5mg/kg for
      suspected eosinophilic peritonitis produced significant improvement of the
      cutaneous eruption. Recurrence of the bullous eruption was observed upon dose
      reduction of the corticosteroid. Skin histology showed a clinical picture of
      eczema and direct immunofluorescence was negative. Patch testing was carried out
      using the European Standard Battery comprising antiseptic, cosmetic and plastic
      series; a semi-open test was performed with the dressing used for PD, and ROAT
      was carried out on the povidone iodine (BetadineTM) 10% used for topical care
      during PD. The patch testing and ROAT were positive (++), confirming contact
      dermatitis due to BetadineTM. The eruption totally disappeared on substitution of
      BetadineTM by chlorhexidine for topical antisepsis of the PD catheter, thus
      enabling PD to be continued rather than instituting hemodialysis. DISCUSSION:
      Allergic contact dermatitis around a PD catheter is a rare and little-known
      complication. In the present case, ROAT testing showed sensitization to
      BetadineTM and enabled an alternative antisepsis solution to be found, allowing
      PD to be continued.

PMID- 25999262
TI  - [Kasabach-Merritt phenomenon (KMP) exacerbated by platelet transfusions].

PMID- 25999263
TI  - [Irritant contact dermatitis caused by direct contact with oleander (Nerium
      oleander)].
AB  - BACKGROUND: Although the oleander plant is practically ubiquitous throughout the
      Mediterranean area, very few publications refer to its cutaneous toxicity.
      PATIENTS AND METHODS: Herein, we report two cases of irritant contact dermatitis
      caused by oleander. The patients in question were twins who had oleander leaves
      applied directly to their face for 20minutes. The initial lesions consisted of
      periorbital erythema, followed by the emergence of papules and macules. Vesicles
      and crusts appeared over the ensuing 24hours. Treatment included withdrawal of
      the toxic agent, prescription of oral antihistamines, and the topical application
      of dermocorticoids to the lesions for two weeks. The outcome on the 9th day was
      slightly hypochromic and atrophic. Complete restitutio ad integrum of the skin
      was observed after 30 days. DISCUSSION: In our patients, a joint effect of
      ultraviolet radiation (phytophotodermatitis) and chlorine from the swimming pool
      cannot be ruled out. Although the substances present in oleanders (irritant
      saponins and glycosides) can cause chemical irritant dermatitis, immunological
      reactions cannot be excluded. The lack of signs of systemic toxicity observed is
      the result of the factors governing transdermal diffusion of the toxic glycosides
      found in oleander. CONCLUSION: These two cases provide a timely reminder, both
      for the general public and for healthcare professionals, of the potential
      biohazards of oleander, not only because of its systemic toxicity but also
      because of the risks associated with cutaneous exposure.

PMID- 25999264
TI  - Pathophysiological links, echocardiographic characteristics, and clinical
      implications of QRS morphology in patients with dilated cardiomyopathy.
AB  - Heart failure is an important clinical problem worldwide. There is great interest
      in evaluating the relationship between electrocardiographic variations and
      dilated cardiomyopathy (DCM) since it has been used as a predictor of increased
      morbidity and mortality. The presence of fragmentation in the QRS complexes on 12
      lead electrocardiogram (ECG) was reported as a marker of depolarization
      abnormality in patients with DCM. Previous studies have investigated the relation
      between QRS morphology and DCM. QRS morphology and duration are associated with
      clinical deterioration and increased mortality in patients with DCM. Although
      surface ECG provides valuable information on prognosis of these patients,
      echocardiographic methods have been used for further investigation of patients
      with DCM. The aim of the present review is to provide an overview of the
      pathophysiological links, echocardiographic characteristics and clinical
      implications of QRS morphology in patients with DCM. 

PMID- 25999265
TI  - Antibacterial activity of fresh pomegranate juice against clinical strains of
      Staphylococcus epidermidis.
AB  - BACKGROUND: Polyphenols have received a great deal of attention due to their
      biological functions. Pomegranate (Punica granatum L.) is a polyphenol-rich
      fruit. In the past decade, studies testing the antimicrobial activity of
      pomegranates almost exclusively used solvent extracts instead of fresh
      pomegranate juice (FPJ). The use of FPJ instead of solvent extracts would reduce
      toxicity issues while increasing patient acceptance. We established a model to
      test FPJ as a natural antimicrobial agent. OBJECTIVE: To evaluate the
      antimicrobial activity of FPJ on clinical isolates of multidrug-resistant
      Staphylococcus epidermidis strains. DESIGN: Sixty strains of S. epidermidis
      isolated from ocular infections were grown in the presence of FPJ, and minimum
      inhibitory concentration (MIC) was determined by broth and agar dilution methods.
      RESULTS: FPJ at 20% had a MIC equal to 100% (MIC100%) on all 60 strains tested.
      This inhibition of FPJ was confirmed by the growth kinetics of a multidrug
      resistant strain exposed to different concentrations of FPJ. Additionally, the
      antimicrobial activity of FPJ was compared against commercial beverages
      containing pomegranate: Ocean Spray((r)) had a MIC100% at 20%, followed by Del
      Valle((r)) with a MIC15% at 20% concentration only. The beverages Jumex((r)) and
      Sonrisa((r)) did not have any antimicrobial activity. FPJ had the highest
      polyphenol content and antioxidant capacity. CONCLUSIONS: Overall, FPJ had
      antimicrobial activity, which might be attributed to its high polyphenol content
      and antioxidant capacity.

PMID- 25999266
TI  - Nanocarriers for the delivery of active ingredients and fractions extracted from
      natural products used in traditional Chinese medicine (TCM).
AB  - Traditional Chinese medicine (TCM) has been practiced for thousands of years with
      a recent increase in popularity. Despite promising biological activities of
      active ingredients and fractions from TCM, their poor solubility, poor stability,
      short biological half-life, ease of metabolism and rapid elimination hinder their
      clinical application. Therefore, overcoming these problems to improve the
      therapeutic efficacy of TCM preparations is a major focus of pharmaceutical
      sciences. Recently, nanocarriers have drawn increasing attention for their
      excellent and efficient delivery of active TCM ingredients or fractions. This
      review discusses problems in the delivery of active TCM ingredients or fractions;
      focuses on recent advances in nanocarriers that represent potential solutions to
      these problems, including lipid-based nanoparticles and polymeric, inorganic, and
      hybrid nanocarriers; and discusses unanswered questions in the field and criteria
      for the development of better nanocarriers for the delivery of active TCM
      ingredients or fractions to be focused on in future studies. 

PMID- 25999267
TI  - Childhood Abuse and Mental Health Problems: Does Gender Matter?
AB  - Gender differences in the relationship between mental health problems and
      childhood abuse have long been of interest to researchers. The purpose of the
      present study was to examine gender differences in the relationship between
      childhood abuse and mental health problems among 110 Israeli inmates (50 women
      and 60 men). The findings indicated that female inmates reported higher
      prevalence of physical, emotional, and sexual abuse and were more likely to
      suffer from mental health problems, compared with the male inmates. Additionally,
      the findings revealed that more female than male inmates had parents with mental
      health problems. Female inmates who reported mental health problems in their
      families also reported higher rates of child abuse relative to male inmates with
      a similar family history. 

PMID- 25999269
TI  - Tribute to: Dr. Vivienne Russell, Ph.D. on Attention-Deficit/Hyperactivity
      Disorder (ADHD).

PMID- 25999268
TI  - Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model
      of Parkinson's disease.
AB  - BACKGROUND: To circumvent the challenges associated with delivering large
      compounds directly to the brain for the treatment of Parkinson's disease (PD),
      non-invasive procedures utilizing smaller molecules with protective and/or
      restorative actions on dopaminergic neurons are needed. NEW METHOD: We developed
      a methodology for evaluating the effects of a synthetic neuroactive peptide, DNSP
      11, on the nigrostriatal system using repeated intranasal delivery in both normal
      and a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. RESULTS:
      Normal rats repeatedly administered varying doses of DNSP-11 intranasally for 3
      weeks exhibited a significant increase in dopamine (DA) turnover in both the
      striatum and substantia nigra (SN) at 300MUg, suggestive of a stimulative effect
      of the dopaminergic system. Additionally, a protective effect was observed
      following repeated intranasal administration in 6-OHDA lesioned rats, as
      suggested by: a significant decrease in d-amphetamine-induced rotation at 2
      weeks; a decrease in DA turnover in the lesioned striatum; and an increased
      sparing of tyrosine hydroxylase (TH) positive (+) neurons in a specific sub
      region of the lesioned substantia nigra pars compacta (SNpc). Finally, tracer
      studies showed (125)I-DNSP-11 distributed diffusely throughout the brain,
      including the striatum and SN, as quickly as 30min after a single intranasal
      dose. COMPARISON WITH EXISTING METHODS: The results of bilateral intranasal
      administration of DNSP-11 are compared to our unilateral single infusion studies
      to the brain in rats. CONCLUSIONS: These studies support that DNSP-11 can be
      delivered intranasally and maintain its neuroactive properties in both normal
      rats and in a unilateral 6-OHDA rat model of PD.

PMID- 25999270
TI  - A functional-dynamic reflection on participatory processes in modeling projects.
AB  - The participation of nonscientists in modeling projects/studies is increasingly
      employed to fulfill different functions. However, it is not well investigated if
      and how explicitly these functions and the dynamics of a participatory process
      are reflected by modeling projects in particular. In this review study, I explore
      participatory modeling projects from a functional-dynamic process perspective.
      The main differences among projects relate to the functions of participation-most
      often, more than one per project can be identified, along with the degree of
      explicit reflection (i.e., awareness and anticipation) on the dynamic process
      perspective. Moreover, two main approaches are revealed: participatory modeling
      covering diverse approaches and companion modeling. It becomes apparent that the
      degree of reflection on the participatory process itself is not always explicit
      and perfectly visible in the descriptions of the modeling projects. Thus, the use
      of common protocols or templates is discussed to facilitate project planning, as
      well as the publication of project results. A generic template may help, not in
      providing details of a project or model development, but in explicitly reflecting
      on the participatory process. It can serve to systematize the particular
      project's approach to stakeholder collaboration, and thus quality management. 

PMID- 25999271
TI  - Deciphering the death of Jean-Francois Champollion (1790-1832), the man who
      decoded ancient Egyptian hieroglyphs.

PMID- 25999272
TI  - Glance backward before forging ahead: Strategically mapping SCAI's future.

PMID- 25999273
TI  - The radialist's religious fervor: Praise the Lord, I Am a Believer in Treating
      CTOs and the Radial Approach.

PMID- 25999274
TI  - Experience and accuracy can result in parity of outcomes following one or two
      stents for left main stem bifurcation disease.

PMID- 25999275
TI  - Bioresorbable drug-eluting scaffold restenosis: Larger Is Probably Better.

PMID- 25999276
TI  - Radiation safety: Patients First "Where Is the Radiation Needle on the Ethical
      Compass?".

PMID- 25999277
TI  - Effective radiation dose in coronary imaging modalities: Back to Basics.

PMID- 25999278
TI  - Minimizing acute kidney injury during TAVR: The Importance of Seeing the Trees
      and the Forest.

PMID- 25999279
TI  - Expanding the armamentarium for effective PFO closure.

PMID- 25999281
TI  - Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in
      human lung fibroblasts.
AB  - COPD lung is characterized by loss of alveolar elastic fibers and an increase in
      the chondroitin sulfate (CS) matrix proteoglycan versican V1 (V1). V1 is a known
      inhibitor of elastic fiber deposition and this study investigates the effects of
      knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with
      cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast
      proliferation, viability, tropoelastin synthesis, and elastin deposition, and
      increased V1 synthesis and secretion. V1 siRNA decreased V1 and constituent CS,
      did not affect tropoelastin production, but blocked the CSE-induced loss in
      insoluble elastin. Exogenous CS reduced insoluble elastin, even in the presence
      of V1 siRNA. These findings confirm that V1 and CS impair the assembly of
      tropoelastin monomers into insoluble fibers, and further demonstrate that
      specific knockdown of V1 alleviates the impaired assembly of elastin seen in
      cultures of pulmonary fibroblasts exposed to CSE, indicating a regulatory role
      for this protein in the pathophysiology of COPD. 

PMID- 25999280
TI  - Association Between TRAF6 Gene Polymorphisms and Susceptibility of Ischemic
      Stroke in Southern Chinese Han Population.
AB  - The tumor necrosis factor receptor-associated factor 6 (TRAF6) gene encodes a
      protein that acts downstream of the Toll-like receptor (TLR) pathway. TLRs
      activate inflammatory cascades and mediate inflammatory injury after cerebral
      ischemia. However, the role of TFAR6 gene polymorphisms in ischemic stroke (IS)
      remains unknown. This study aims to investigate the associations of TRAF6 gene
      polymorphisms with susceptibility to IS and IS-related quantitative traits in
      Southern Chinese Han population. A total of 816 IS cases and 816 age- and gender
      matched controls were included. Two variants of the TRAF6 gene (rs5030411 and
      rs5030416) were genotyped using the Sequenom MassARRAY iPLEX platform. Our study
      showed that rs5030416 was significantly associated with increased susceptibility
      to IS in the additive model [ORadj 1.25(1.04-1.51), P adj = 0.019, P Bc = 0.038]
      and dominant model [ORadj 1.23(1.04-1.60), P adj = 0.021, P Bc = 0.042] after
      adjusting by age and sex and applying a Bonferroni correction. No significant
      association was found between rs5030411 and IS susceptibility (all P > 0.05). The
      haplotype rs5030416 (allele C)-rs5030411 (allele C) was significantly associated
      with IS susceptibility (P adj = 0.015). Moreover, a significant association of
      rs5030411 with TC levels in IS patients under the additive model [beta 0.16(0.01
      0.30), P adj = 0.034] and recessive model [beta 0.45(0.12-0.78), P adj = 0.007]
      was observed after adjustment by age and sex. This association remained
      statistically significant under the recessive model (P Bc = 0.042) after
      Bonferroni correction. Our results suggest that TRAF6 gene polymorphisms may be
      involved in the pathogenesis of IS.

PMID- 25999282
TI  - Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective
      effects against brain injury in a rat model of neonatal hypoxic-ischemic
      encephalopathy.
AB  - Neonatal hypoxic-ischemic (HI) brain injury causes severe brain damage in
      newborns. Following HI injury, rapidly accumulating oxidants injure neurons and
      interrupt ongoing developmental processes. The antioxidant, sodium pyruvate, has
      been shown to reduce neuronal injury in neonatal rats under conditions of oxygen
      glucose deprivation (OGD) and HI injury. In this study, we evaluated the effects
      of ethyl pyruvate (EP) and insulin-like growth factor-I (IGF-I) alone or in
      combination in a similar setting. For this purpose, we used an in vitro model
      involving primary neonatal rat cortical neurons subjected to OGD for 2.5 h and an
      in vivo model involving unilateral carotid ligation in rats on post-natal day 7
      with exposure to 8% hypoxia for 2.5 h. The cultured neurons were examined by
      lactate dehydrogenase (LDH) and cell viability assays. For the in vivo
      experiments, behavioral development was evaluated by the foot fault test at 4
      weeks of recovery. 2,3,5-Triphenyltetrazolium chloride monohydrate and cresyl
      violet staining were used to evaluate HI injury. The injured neurons were Fluoro
      Jade B-labeled, new neuroprecursors were double labeled with bromodeoxyuridine
      (BrdU) and doublecortin, new mature neurons were BrdU-labeled and neuronal nuclei
      were labeled by immunofluorescence. Under conditions of OGD, the LDH levels
      increased and neuronal viability decreased. Treatment with 0.5 mM EP or 25 ng/ml
      IGF-I protected the neurons (P<0.05), exerting additive effects. Similarly,
      either the early administration of EP or delayed treatment with IGF-I protected
      the neonatal rat brains against HI injury and improved neurological performance
      and these effects were also additive. This effect may be the result of reduced
      neuronal injury, and enhanced neurogenesis and maturation. On the whole, our
      findings demonstrate that the combination of the early administration of EP with
      delayed treatment with IGF-I exerts neuroprotective effects against HI injury in
      neonatal rat brains.

PMID- 25999283
TI  - Guillain-Barre syndrome and influenza vaccines: A meta-analysis.
AB  - Cases of Guillain-Barre syndrome (GBS) have been occasionally associated with
      influenza vaccines; this possible risk, even if rare, is a matter of much
      concern. To investigate the strength of this association, a systematic review and
      a meta-analysis have been conducted; for the purpose, controlled observational
      studies addressing the risk of GBS associated with different influenza vaccines
      were sought. We finally selected 39 studies of interest published between 1981
      and 2014 (seasonal influenza vaccines, 22; pandemic influenza vaccines, 16; both
      vaccines simultaneously administered, 1); funnel plot did not identify
      publication bias. At the association between any influenza vaccine - whether
      seasonal or pandemic - with GBS, the overall relative risk was 1.41 (95% CI, 1.20
      1.66). Pandemic vaccines presented a higher risk (RR=1.84; 95% CI, 1.36-2.50)
      compared to seasonal vaccines (RR=1.22; 95% CI, 1.01-1.48); the latter should be
      considered as marginally statistically significant. Pandemic adjuvanted vaccines
      were not found to be related to a higher risk compared to non-adjuvanted
      vaccines. The results of the present meta-analysis point to a small but
      statistically significant association between influenza vaccines, particularly
      the pandemic ones, and GBS, which is consistent with current explanations upon
      possible mechanisms for this condition to appear. 

PMID- 25999284
TI  - Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production
      without loss of antigenicity or immunogenicity.
AB  - The recently detected zoonotic H3N2 variant influenza A (H3N2v) viruses have
      caused 343 documented cases of human infection linked to contact with swine. An
      effective vaccine is needed for these viruses, which may acquire transmissibility
      among humans. However, viruses isolated from human cases do not replicate well in
      embryonated chicken eggs, posing an obstacle to egg-based vaccine production. To
      address this issue, we sought to identify egg-adaptive mutations in surface
      proteins that increase the yield of candidate vaccine viruses (CVVs) in eggs
      while preserving their immunizing effectiveness. After serial passage of a
      representative H3N2v isolate (A/Indiana/08/2011), we identified several egg
      adaptive combinations of HA mutations and assessed the egg-based replication,
      antigenicity, and immunogenicity of A/Puerto Rico/8/34 (H1N1, PR8)-based 6+2
      reverse genetics CVVs carrying these mutations. Here we demonstrate that the
      respective combined HA substitutions G1861V+N2461K, N1651K+G1861V,
      T1281N+N1651K+R762G, and T1281N+N1651K+I102M, all identified after egg passage,
      enhanced the replication of the CVVs in eggs without substantially affecting
      their antigenicity or immunogenicity. The mutations were stable, and the mutant
      viruses acquired no additional substitutions during six subsequent egg passages.
      We found two crucial mutations, G186V, which was previously defined, and N246K,
      which in combination improved virus yield in eggs without significantly impacting
      antigenicity or immunogenicity. This combination of egg-adaptive mutations
      appears to most effectively generate high egg-based yields of influenza
      A/Indiana/08/2011-like CVVs. 

PMID- 25999285
TI  - The fibroblast growth factor-2 arrests Mycobacterium avium sp. paratuberculosis
      growth and immunomodulates host response in macrophages.
AB  - Mycobacterium tuberculosisis (M. tb) epidemic is one of the most severe health
      problem worldwide, while mechanisms underlying its pathogenesis and host immune
      responses remain unclear. Mycobacterium avium (M. avium), a mycobacterial species
      related to M. tb, shares similarities with M. tb in many ways. In this study,
      using M. avium infection of macrophages as a model, we systematically studied the
      effect of fibroblast growth factor-2 (FGF-2) on M. avium infection of
      macrophages. Our results showed that M. avium infection could increase FGF-2
      expression on both mRNA and protein levels. M. avium infection elevated TNF-alpha
      and IFN-gamma production while the addition of FGF-2 could further increase TNF
      alpha but not IFN-gamma level. M. avium infection could increase the expression
      of oxygen/nitrogen metabolism proteins iNOS and SOD-1, and FGF-2 had additive
      effect on the expression of these two proteins. M. avium infection had inhibitive
      effect on actin expression while FGF-2 could partly counteract such inhibition.
      Moreover, FGF-2 could inhibit M. avium proliferation in macrophages. Our results
      together indicate that macrophage-secreted FGF-2 upon M. avium infection could
      suppress M. avium proliferation through various ways including cytokine
      production, enhancement of phagocytosis as well as oxygen/nitrogen metabolism. 

PMID- 25999286
TI  - The mycobacterial PhoH2 proteins are type II toxin antitoxins coupled to RNA
      helicase domains.
AB  - PhoH2 proteins are found in a diverse range of organisms that span the bacterial
      tree and little is known about this large protein family. PhoH2 proteins have two
      domains: An N-terminal PIN domain fused to a C-terminal PhoH domain. The genome
      of Mycobacterium tuberculosis encodes 48 PIN domains and 47 of these constitute
      the VapC components of the 47 VapBC toxin-antitoxins. The 48th member of the M.
      tuberculosis PIN domain array is found in the single PhoH2 protein encoded in the
      genome. All characterized PIN domain proteins are RNases and the PhoH domains are
      predicted ATPases. This fusion of a PIN domain with an ATPase reflects a much
      wider association between PIN domains and PhoH domains across many prokaryote
      genomes. Here, we examine PhoH2 proteins from M. tuberculosis, Mycobacterium
      smegmatis and a thermophilic homologue from Thermobispora bispora and we show
      that PhoH2 is a sequence-specific RNA helicase and RNAse. In addition, phoH2 from
      M. tuberculosis and M. smegmatis is part of a longer mRNA transcript which
      includes a small, unannotated open reading frame (ORF) upstream of the phoH2
      gene. This small gene overlaps with the beginning of the phoH2 gene in a manner
      similar to the PIN domain toxin-antitoxin operons. We have annotated the upstream
      gene as phoAT and its putative promoter elements satisfy previously characterized
      consensus sequences at the -10 site. Conditional growth experiments carried out
      in M. smegmatis revealed a negative effect on growth by the expression of M.
      tuberculosis PhoH2 that was alleviated by co-expression of the PhoAT peptide.
      Thus in M. tuberculosis, PhoH2 represents a new variation on a type II PIN domain
      toxin-antitoxin systems such that the toxin-antitoxin is now coupled to an RNA
      helicase whose predicted biological function is to unwind and cleave RNA in a
      sequence specific manner. 

PMID- 25999287
TI  - Evaluation of standardization capability of current cardiac troponin I assays by
      a correlation study: results of an IFCC pilot project.
AB  - BACKGROUND: As a part of an International Federation of Clinical Chemistry and
      Laboratory Medicine (IFCC) project to prepare a commutable reference material for
      cardiac troponin I (cTnI), a pilot study evaluated current cTnI assays for
      measurement equivalence and their standardization capability. METHODS: cTnI
      positive samples collected from 90 patients with suspected acute myocardial
      infarction were assessed for method comparison by 16 cTnI commercial assays
      according to predefined testing protocols. Seven serum pools prepared from these
      samples were also assessed. RESULTS: Each assay was assessed against median cTnI
      concentrations measured by 16 cTnI assays using Passing-Bablok regression
      analysis of 79 patient samples with values above each assay's declared detection
      limit. We observed a 10-fold difference in cTnI concentrations for lowest to
      highest measurement results. After mathematical recalibration of assays, the
      between-assay variation for patient samples reduced on average from 40% to 22% at
      low cTnI concentration, 37%-20% at medium concentration, and 29%-14% at high
      concentration. The average reduction for pools was larger at 16%, 13% and 7% for
      low, medium and high cTnI concentrations, respectively. Overall, assays
      demonstrated negligible bias after recalibration (y-intercept: -1.4 to 0.3 ng/L);
      however, a few samples showed substantial positive and/or negative differences
      for individual cTnI assays. CONCLUSIONS: All of the 16 commercial cTnI assays
      evaluated in the study demonstrated a significantly higher degree of measurement
      equivalence after mathematical recalibration, indicating that measurement
      harmonization or standardization would be effective at reducing inter-assay bias.
      Pooled sera behaved similarly to individual samples in most assays.

PMID- 25999288
TI  - Adaptive deep brain stimulation in a freely moving Parkinsonian patient.

PMID- 25999289
TI  - Fabrication of a novel nanocomposite Ag/graphene@SiO2-NaLuF4:Yb,Gd,Er for large
      enhancement upconversion luminescence.
AB  - Upconversion nanocrystals have a lot of advantages over other fluorescent
      materials. However, their applications are still limited due to their
      comparatively low upconversion luminescence (UCL). In the present study, a novel
      nanocomposite of Ag/graphene@SiO2-NaLuF4:Yb,Gd,Er for enhancing UCL was
      fabricated successfully, and its morphology, crystalline phase, composition, and
      fluorescent property were investigated. It is interesting to find that the
      Ag/graphene@SiO2-NaLuF4:Yb,Gd,Er and Ag@SiO2-NaLuF4:Yb,Gd,Er nanocomposites
      showed high UCL enhancements of 52- and 10-fold compared to the control of Ag
      free nanocomposite SiO2-NaLuF4:Yb,Gd,Er, respectively. The enhancement of 52-fold
      is greater than those reported in our previous studies and some papers. Moreover,
      the measured life times of the Ag-presented nanocrystals were longer than that of
      Ag-absent counterparts. These enhancements of UCL can be ascribed to the effect
      of metal-enhanced fluorescence, which is caused by the enhancement of the local
      electric field. The UCL intensity of Ag/graphene@SiO2-NaLuF4:Yb,Gd,Er was 5.2
      fold higher than that of Ag@SiO2-NaLuF4:Yb,Gd,Er, indicating that graphene
      presented in the fabricated nanocomposite structure favors metal-enhanced UCL.
      The small-sized Ag nanoparticles anchored on the graphene sheet mutually enhanced
      each other's polarizability and surface plasmon resonance, resulting in a big
      metal-enhanced UCL. This study provides a new strategy for effectively enhancing
      the UCL of upconversion nanocrystals. The enhancement potentially increases the
      overall upconversion nanocrystal detectability for highly sensitive biological,
      medical, and optical detections. 

PMID- 25999290
TI  - Editorial. Production and utilization of H2O2 in protein folding.

PMID- 25999291
TI  - The effects of tamoxifen and soy on dark neuron production in hippocampal
      formation after pentylenetetrazole-induced repeated seizures in rats.
AB  - BACKGROUND: Regarding the similar modulatory effects of both soy and tamoxifen on
      the actions of estrogen which have previously reported, the aim of the present
      study was to investigate the effects of these two estrogen like compounds alone
      and in combination on dark neuron production in hippocampal formation of
      ovariectomized rats after pentylenetetrazole-induced repeated seizure. METHODS:
      The rats were randomly divided into six groups: control, sham, OVX, OVX-soy (OVX
      S), OVX-tamoxifen (OVX-T) and OVX-soy-tamoxifen (OVX-S-T). The animals of OVX-S,
      OVX-T and OVX-S-T groups received the soy extract (60mg/kg; i.p.), tamoxifen
      (10mg/kg) or both for 2 weeks before induction of seizures. The animals of these
      groups were also treated by soy extract, tamoxifen or both before each injection
      of PTZ (40mg/kg) for 6 days. The animals of sham and OVX groups received saline
      plus tween instead of tamoxifen and soy extract. The animals of control group did
      not treat by PTZ, tamoxifen and soy. The rats were placed in Plexiglas cages
      separately and observed for 60min. The brain tissues were then removed and
      subjected for histological studies. RESULTS: A significant decrease in the
      seizure score was seen in OVX group comparing to sham. The animals of both OVX-T
      and OVX-S groups had a significant higher seizure score compared to OVX group. Co
      treatment of the ovariectomized rats by both soy extract and tamoxifen decreased
      the seizure score compared to OVX-S and OVX-T groups. The results of histological
      study showed that the dark neuron number in CA1, CA2, CA3 and dentate gyrus (DG)
      of hippocampus area in OVX-T and OVX-S groups was higher than that of OVX group
      (P<0.05-P<0.01). In CA3, the produced dark neurons of OVX-S-T group were lower
      than that OVX-S group (P<0.01). CONCLUSION: The results of present study showed
      that treatment of the ovariectomized rats by either soy extract or tamoxifen
      increased the seizure score as well as dark neurons. Co-treatment with soy
      extract and tamoxifen did not potentiate the effects of each of them alone. Co
      administration of the tamoxifen and soy extract inhibited the effects of the soy
      extract and tamoxifen when they administered alone.

PMID- 25999292
TI  - Functional outcomes from a head-to-head, randomized, double-blind trial of
      lisdexamfetamine dimesylate and atomoxetine in children and adolescents with
      attention-deficit/hyperactivity disorder and an inadequate response to
      methylphenidate.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is associated with functional
      impairments in multiple domains of patients' lives. A secondary objective of this
      randomized, active-controlled, head-to-head, double-blind, dose-optimized
      clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX)
      and atomoxetine (ATX) on functional impairment in children and adolescents with
      ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score >= 28 and
      an inadequate response to methylphenidate treatment (judged by investigators)
      were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians
      completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at
      baseline and at week 9 or early termination. p values were nominal and not
      corrected for multiple comparisons. Of 267 randomized patients, 200 completed the
      study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group
      was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03]
      and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains
      improved from baseline to endpoint in both groups, with least-squares mean
      changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, 
      0.20) for ATX. The difference between LDX and ATX was statistically significant
      (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and
      Social Activities (0.34) domains and for total score (0.27). Both treatments
      reduced functional impairment in children and adolescents with ADHD; LDX was
      statistically significantly more effective than ATX in two of six domains and in
      total score.

PMID- 25999293
TI  - Calreticulin is required for responding to stress, foraging, and fertility in the
      white-tip nematode, Aphelenchoides besseyi.
AB  - Calreticulin (CRT) regulates a wide array of cellular responses in physiological
      and pathological processes. A full-length cDNA-encoding CRT protein, namely AbCRT
      1, was isolated from Aphelenchoides besseyi, an ectoparasitic plant nematode and
      the agent of white tip disease of rice. The deduced amino acid sequence of AbCRT
      1 was highly homologous with other nematode CRTs, and showed the closest
      evolutionary relationship with BxCRT-1. In-situ hybridization showed that AbCRT-1
      is specifically located in the oesophageal gland and gonads of A. besseyi,
      suggesting its potential role in parasitism and reproduction. Quantity real-time
      PCR analysis showed that AbCRT-1 is highly expressed in female nematodes but
      poorly expressed in eggs, juveniles, and male nematodes. Exposing the nematode to
      relatively low osmotic stress promotes the transcription of AbCRT-1 whereas
      extreme desiccation suppresses the transcription significantly. Nematodes in
      which AbCRT-1 mRNA level had been knocked down by soaking them in AbCRT-1 dsRNA
      solution distributed randomly and did not aggregate temporally, with a decreased
      capacity of food discernment. Thus the affected nematodes were markedly less
      fecund. These results demonstrate that AbCRT-1 is required in A. besseyi for
      responding to stress, foraging, and fertility. 

PMID- 25999294
TI  - Intrinsically disordered energy landscapes.
AB  - Analysis of an intrinsically disordered protein (IDP) reveals an underlying
      multifunnel structure for the energy landscape. We suggest that such
      'intrinsically disordered' landscapes, with a number of very different competing
      low-energy structures, are likely to characterise IDPs, and provide a useful way
      to address their properties. In particular, IDPs are present in many cellular
      protein interaction networks, and several questions arise regarding how they bind
      to partners. Are conformations resembling the bound structure selected for
      binding, or does further folding occur on binding the partner in a induced-fit
      fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein,
      which adopts an alpha-helical conformation when bound to its partner, and is
      involved in the activation of apoptosis. Recent experimental evidence shows that
      folding is not necessary for binding, and supports an induced-fit mechanism.
      Using a variety of computational approaches we deduce the molecular mechanism
      behind the instability of the PUMA peptide as a helix in isolation. We find
      significant barriers between partially folded states and the helix. Our results
      show that the favoured conformations are molten-globule like, stabilised by
      charged and hydrophobic contacts, with structures resembling the bound state
      relatively unpopulated in equilibrium.

PMID- 25999295
TI  - Analysis of accelerated failure time data with dependent censoring using
      auxiliary variables via nonparametric multiple imputation.
AB  - We consider the situation of estimating the marginal survival distribution from
      censored data subject to dependent censoring using auxiliary variables. We had
      previously developed a nonparametric multiple imputation approach. The method
      used two working proportional hazards (PH) models, one for the event times and
      the other for the censoring times, to define a nearest neighbor imputing risk
      set. This risk set was then used to impute failure times for censored
      observations. Here, we adapt the method to the situation where the event and
      censoring times follow accelerated failure time models and propose to use the
      Buckley-James estimator as the two working models. Besides studying the
      performances of the proposed method, we also compare the proposed method with two
      popular methods for handling dependent censoring through the use of auxiliary
      variables, inverse probability of censoring weighted and parametric multiple
      imputation methods, to shed light on the use of them. In a simulation study with
      time-independent auxiliary variables, we show that all approaches can reduce bias
      due to dependent censoring. The proposed method is robust to misspecification of
      either one of the two working models and their link function. This indicates that
      a working proportional hazards model is preferred because it is more cumbersome
      to fit an accelerated failure time model. In contrast, the inverse probability of
      censoring weighted method is not robust to misspecification of the link function
      of the censoring time model. The parametric imputation methods rely on the
      specification of the event time model. The approaches are applied to a prostate
      cancer dataset.

PMID- 25999296
TI  - The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive
      like behavior in 6-OHDA animal model of Parkinson's disease.
AB  - Depression is one of the most common psychiatric symptoms in patients with
      Parkinson's disease (PD). Some authors have reported that depression is
      characterized by activation of the inflammatory response. Animal models of PD
      also present with depressive-like behavior, such as increased immobility time in
      the modified forced swim test and anhedonia-like behavior in the sucrose
      preference test. Considering the potential neuroprotective effect of nonsteroidal
      antiinflammatory drugs in neurodegenerative diseases, the objective of the
      present study was to investigate the effects of piroxicam on depressive-like
      behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the
      substantia nigra (SN). Antidepressant-like effects were observed after prolonged
      administration of piroxicam for 21days. In the forced swim test, the 6
      OHDA+saline group exhibited significant reductions in swimming time and increased
      immobility time compared with the sham+saline. In the sucrose preference test,
      the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared
      with the sham+saline, with significant effects of treatment and time and a
      significant treatment*time interaction. 5-Hydroxytryptamine (5-HT) levels
      significantly decreased in the hippocampus in the 6-OHDA+saline group and not
      changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day
      21. In conclusion, 21-day treatment with piroxicam reversed the onset of
      depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.

PMID- 25999297
TI  - The protein tyrosine phosphatase interacting protein 51 (PTPIP51) is required for
      the differentiation of photoreceptors.
AB  - Proliferation and differentiation of retinal progenitor cells (RPCs) are tightly
      controlled by extrinsic cues and distinct combinations of transcription factors
      leading to the generation of retinal cell type diversity. In this context, we
      investigated the role of the protein tyrosine phosphatase interacting protein 51
      (PTPIP51) in the differentiation of RPCs. The expression pattern of PTPIP51 was
      analyzed by immunostaining during post-natal retinal development in the rat. Ex
      vivo electroporation has been used to silence or misexpress PTPIP51 in post-natal
      retinal explants, and the retinal phenotype was investigated after 3-7days in
      vitro (div). PTPIP51 expression in the retina started postnatally and was
      maintained throughout adulthood, especially in retinal ganglion cells and in the
      inner segment of photoreceptor cells. Silencing of Ptpip51 expression in
      postnatal retina failed to modify the commitment of late RPCs in the different
      lineages but severely impaired the final differentiation of photoreceptors,
      observed by a decrease in the fraction of Rhodopsin-positive cells after 7div. By
      contrast, misexpression of PTPIP51 in early or late RPCs failed to modify the
      differentiation of the RPCs. Our data demonstrate that PTPIP51 is implicated in
      the differentiation process of immature photoreceptors. Because PTPIP51 is
      specifically localized in the inner segment, PTPIP51 may contribute to the
      complex stage of maturation of the apical segment of these cells.

PMID- 25999298
TI  - Swiss physicians' attitudes to assisted suicide: A qualitative and quantitative
      empirical study.
AB  - PRINCIPLES: In Switzerland, assisted suicide is legal as long as it does not
      involve self-serving motives. Physician-assisted suicide is regulated by specific
      guidelines issued by the Swiss Academy of Medical Sciences (SAMS). This article
      summarises the results of an empirical study of physicians' attitudes to assisted
      suicide in Switzerland, which was commissioned by the SAMS. The study (in German)
      is available online at: www.samw.ch. METHODS: Twelve qualitative interviews and a
      written survey were conducted, involving a disproportional, stratified random
      sample of Swiss physicians (4,837 contacted, 1,318 respondents, response rate
      27%). RESULTS: Due to the response rate and the wide variation of respondents
      from one professional speciality to another, the findings and interpretations
      presented should be regarded as applying only to the group of physicians who are
      interested in or are particularly affected by the issue of assisted suicide. They
      cannot be generalised to the whole body of physicians in Switzerland. Of the
      respondents, 77% considered physician-assisted suicide to be justifiable in
      principle, while 22% were fundamentally opposed to it. Although 43% could imagine
      situations where they would personally be prepared to perform assisted suicide,
      it is clear from the study that this potential readiness does not mean that all
      respondents would automatically be prepared to perform it in practice as soon as
      the legal criteria are met. The vast majority of respondents emphasised that
      there should be no obligation to perform physician-assisted suicide. Opinions
      differed as to whether physician-assisted suicide should remain restricted to
      cases where the person concerned is approaching the end of life. While a large
      majority of respondents considered physician-assisted suicide also to be
      justifiable in principle in non-end-of-life situations, 74% supported the
      maintenance of the end-of-life criterion in the SAMS Guidelines as a necessary
      condition for physician-assisted suicide. Over 50% of the respondents had never
      been confronted with a request for assisted suicide by a patient. CONCLUSIONS:
      The vast majority of physicians surveyed considered assisted suicide to be
      justifiable in principle; however, their support was strongly dependent on the
      specific situation. The study indicates that even physicians expressing a
      potential readiness to perform assisted suicide themselves would not do so
      automatically if all the criteria for assisted suicide were met. Assisted suicide
      thus appears to be an exceptional situation, which physicians would only become
      involved in on a voluntary basis. The authors recommend that the current SAMS
      Guidelines regulating physician-assisted suicide in Switzerland should be
      reviewed with regard to the end-of-life criterion as a necessary condition for
      physician-assisted suicide.

PMID- 25999299
TI  - Occurrence and new mutations involved in rifampicin-resistant Propionibacterium
      acnes strains isolated from biofilm or device-related infections.
AB  - We described for the first time the amino acid substitutions conferring
      rifampicin resistance in eight Propionibacterium acnes strains isolated from
      patients with biofilm or device-related infections. We identified different
      mutations in cluster I and one mutation, never reported, in cluster II of the
      rpoB gene (I480V) associated with the most frequent one in cluster I (S442L).
      Half of the patients previously received treatment with rifampicin. 

PMID- 25999300
TI  - Diurnal Salivary Cortisol and Regression Status in MECP2 Duplication Syndrome.
AB  - MECP2 duplication syndrome is an X-linked genomic disorder that is characterized
      by infantile hypotonia, intellectual disability, and recurrent respiratory
      infections. Regression affects a subset of individuals, and the etiology of
      regression has yet to be examined. In this study, alterations in the hypothalamus
      pituitary-adrenal axis, including diurnal patterns in salivary cortisol, were
      examined in 4 males with MECP2 duplication syndrome who had regression and 4
      males with the same syndrome without regression (aged 3-22 years). Individuals
      who had experienced regression do not exhibit typical diurnal cortisol rhythms,
      and their profiles were flatter through the day. In contrast, individuals with
      MECP2 duplication syndrome who had not experienced regression showed more typical
      patterns of higher cortisol levels in the morning with linear decreases
      throughout the day. This study is the first to suggest a link between atypical
      diurnal cortisol rhythms and regression status in MECP2 duplication syndrome and
      may have implications for treatment. 

PMID- 25999301
TI  - Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine
      Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and
      Spastic Equinus Foot Deformity.
AB  - This retrospective study aimed to compare the therapeutic response, including
      side effects, for oral baclofen versus oral tizanidine therapy with adjuvant
      botulinum toxin type A in a group of 64 pediatric patients diagnosed with static
      encephalopathy and spastic equinus foot deformity. Following botulinum toxin A
      treatment, clinical improvement led to the gradual reduction of baclofen or
      tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure
      and Caregiver Health Questionnaire scores were markedly elevated post-botulinum
      toxin A treatment, with scores for the tizanidine (Gross Motor Functional
      Measure: 74.45 +/- 3.72; Caregiver Health Questionnaire: 72.43 +/- 4.29) group
      significantly higher than for the baclofen group (Gross Motor Functional Measure:
      68.23 +/- 2.66; Caregiver Health Questionnaire: 67.53 +/- 2.67, P < .001). These
      findings suggest that the combined use of botulinum toxin A and a low dose of
      tizanidine in treating children with cerebral palsy appears to be more effective
      and has fewer side effects versus baclofen with adjuvant botulinum toxin A. 

PMID- 25999302
TI  - Do Patients Require Inpatient Admission to Receive Adrenocorticotropic Hormone
      (ACTH)? A Survey of US-Based Prescribers.
AB  - We aimed to determine variation in treatment of newly diagnosed infantile spasms,
      focusing on details of adrenocorticotropic hormone (ACTH) administration using a
      Redcap questionnaire sent to members of the Child Neurology Society. Two hundred
      fifty-seven members responded. Eighty-four percent prescribers used ACTH to treat
      infantile spasms. Seventy-six percent always admit patients. There is no
      difference between prescriber type (epileptologist or other) and prescriber
      location (state-funded or non-state-funded hospital) for decision to admit.
      Electroencephalographic (EEG) confirmation of spasms and education for injection
      were the commonest reasons to admit. Only 45% of prescribers accurately estimated
      the cost of ACTH. Participants in the hospital vial program were significantly
      more likely to always admit patients for ACTH than those who did not participate
      in such a program (P = .02). Although having the hospital sample vial allows time
      to complete investigation of infantile spasms and eliminates delays in initiating
      ACTH, it adds significantly to the cost of therapy. 

PMID- 25999303
TI  - Pressure-induced normal-incommensurate and incommensurate-commensurate phase
      transitions in CrOCl.
AB  - The high-pressure behavior of layered CrOCl is shown to be governed by non-bonded
      interactions between chlorine atoms in relation to a rigid framework composed of
      Cr and O atoms. The competition between optimizing intra- and interlayer Cl-Cl
      distances and the general trend towards denser packing defines a novel mechanism
      for high-pressure phase transitions of inorganic materials. CrOCl possesses an
      incommensurate phase for 16-51 GPa. Single-crystal x-ray diffraction in a diamond
      anvil cell provides an accurate description of the evolution of the
      incommensurate wave with pressure. It thus demonstrates a continuous increase of
      the amplitude up to 30 GPa, followed by a decrease of the wavelength until a lock
      in transition occurs at 51 GPa.

PMID- 25999304
TI  - Effects of glutamate on growth, antioxidant capacity, and antioxidant-related
      signaling molecule expression in primary cultures of fish enterocytes.
AB  - The present study explored the effects of glutamate (Glu) on the growth,
      antioxidant capacity, and gene expression of NF-E2-related nuclear factor 2
      (Nrf2) signaling molecule in enterocytes of Jian carp (Cyprinus carpio var.
      Jian). The enterocytes were incubated in media containing 0, 2, 4, 6, 8, and 10
      mM/L Glu for 96 h. The results showed that Glu could promote fish enterocytes
      proliferation and differentiation. Additionally, activities of alkaline
      phosphatase, Na(+), K(+)-ATPase, gamma-glutamyl transpeptidase, and creatine
      kinase were significantly improved with the increase in Glu level up to 6 mM/L.
      Lactic acid dehydrogenase activity and malondialdehyde content in the medium and
      cellular protein carbonyls were depressed by Glu. Moreover, optimum Glu
      significantly enhanced glutathione content and the activities and gene expression
      of catalase, glutathione reductase, and glutathione peroxidase in enterocytes.
      Finally, the expression level of Nrf2 in enterocytes was significantly elevated
      by appropriate Glu content in the medium. Furthermore, optimum Glu significantly
      decreased Kelch-like ECH-associated protein 1 mRNA level in enterocytes. In
      conclusion, Glu improved the proliferation, function, and antioxidant capacity
      and regulated antioxidant-related signaling molecule expression of fish
      enterocytes. 

PMID- 25999305
TI  - Turkish version of the Johns Hopkins Restless Legs Syndrome Quality of Life
      Questionnaire (RLS-QoL): validity and reliability study.
AB  - BACKGROUND AND PURPOSE: Restless legs syndrome (RLS), as well as problems
      secondary to RLS, may worsen the quality of life. Our aim was to modify the
      Restless Legs Syndrome Quality of Life (RLS-QoL) questionnaire advanced by Abetz
      (Health Qual Life Outcomes 3:79, 2005) and to analyse the validity and
      reliability of the questionnaire. METHODS: Two hundred and one consecutive
      patients with RLS and forty-three control subjects were included in the study.
      Permission regarding the translation and validation of the RLS-QoL questionnaire
      was obtained. The translation was conducted according to the guidelines provided
      by the publisher. RESULTS: For the RLS subjects, the mean Insomnia Severity Index
      (ISI) score, the International Restless Legs Syndrome Severity Rating Scale
      (IRLSSG) score and the computed score of the RLS-QoL questionnaire were 22.60 +/-
      3.39, 24.83 +/- 5.28 and 45.93 +/- 17.62, respectively. Among the RLS subjects
      without insomnia, the mean (+/-standard deviation) ISI score, IRLSSG score and
      computed score of the RLS-QoL questionnaire were 6.67 +/- 2.34, 15.11 +/- 4.03
      and 41.93 +/- 16.12, respectively. A significant difference was identified
      between both groups on all scores (ISI: p = 0.001, RLS: p = 0.001). The groups
      with and without insomnia were similar regarding the computed score of the RLS
      QoL questionnaire (p = 0.140). According to a correlation analysis, a significant
      correlation was identified between the ISI and IRLSSG or RLS-QoL scores (r =
      0.513, p = 0.001 and r = -0.383, p = 0.001, respectively). Although the
      coefficient of correlation is significant between IRLSSG score and RLS-QoL scale
      score, it should not be considered as a powerful enough correlation (r = 0.190, p
      = 0.007). Most items also exhibited a strong correlation with each other. The
      internal consistency determined by Cronbach's alpha indicated an extremely good
      correlation (0.975). DISCUSSION: These findings suggest the Turkish version of
      the RLS-QoL questionnaire is a valid and reliable tool for the assessment of the
      quality of life in patients with RLS.

PMID- 25999307
TI  - Immunotherapy with G-CSF in patients with chronic mucocutaneous candidiasis.

PMID- 25999306
TI  - Surgical cytoreduction restores the antitumor efficacy of a Listeria
      monocytogenes vaccine in malignant pleural mesothelioma.
AB  - Recent studies suggest that immunotherapy may offer a promising treatment
      strategy for early-stage malignant pleural mesothelioma (MPM), but advanced tumor
      burden may limit the efficacy of immunotherapy. Therefore, we hypothesized that
      surgical cytoreduction could restore the efficacy of vaccine-based immunotherapy
      for MPM. We developed a murine model of MPM through transduction of a
      mesothelioma cell line with mesothelin. We used this model to evaluate the
      efficacy of a Listeria monocytogenes vaccine expressing mesothelin. Tumor growth
      was significantly inhibited at four weeks in animals vaccinated two weeks prior
      to tumor cell inoculation as compared to those given an empty vector control
      (1371 +/- 420 mm(3) versus 405 +/- 139 mm(3); p < 0.01). Mice vaccinated one week
      prior to tumor challenge also displayed significant reduction in tumor volume
      (1227 +/- 406 mm(3) versus 309 +/- 173 mm(3); p < 0.01). The vaccine had no
      effect when administered concurrently with tumor challenge, or after tumors were
      established. Flow cytometry showed reduced mesothelin expression in large tumors,
      as well as tumor-associated immunosuppression due to increased myeloid derived
      suppressor cells (MDSCs). These factors may have limited vaccine efficacy for
      advanced disease. Surgical cytoreduction of established tumors restored the
      antitumor potency of the therapeutic vaccine, with significantly reduced tumor
      burden at post-operative day 18 (397 +/- 103 mm(3) versus 1047 +/- 258 mm(3); p <
      0.01). We found that surgery reduced MDSCs to levels comparable to those in tumor
      naive mice. This study demonstrates that cytoreduction surgery restores the
      efficacy of cancer vaccines for MPM by reducing tumor-related immunosuppression
      that impairs immunotherapy.

PMID- 25999308
TI  - Draft genome of Jeotgalibacillus campisalis SF-57(T), a moderate halophilic
      bacterium isolated from marine saltern.
AB  - Jeotgalibacillus campisalis SF-57(T) (=KCCM 41644(T), JCM 11810(T)) is a moderate
      halophilic bacterium isolated from a Korean marine saltern. In this study, we
      describe the high-quality draft genome of strain SF-57(T), which was assembled
      into 24 contigs containing 3,650,490bp with a G+C content of 41.06%. Availability
      of the genome sequence of J. campisalis SF-57(T) will contribute to a better
      understanding of the genus Jeotgalibacillus. 

PMID- 25999309
TI  - How is the inner circadian clock controlled by interactive clock proteins?:
      Structural analysis of clock proteins elucidates their physiological role.
AB  - Most internationally travelled researchers will have encountered jetlag. If not,
      working odd hours makes most of us feel somehow dysfunctional. How can all this
      be linked to circadian rhythms and circadian clocks? In this review, we define
      circadian clocks, their composition and underlying molecular mechanisms. We
      describe and discuss recent crystal structures of Drosophila and mammalian core
      clock components and the enormous impact they had on the understanding of
      circadian clock mechanisms. Finally, we highlight the importance of circadian
      clocks for the daily regulation of human/mammalian physiology and show
      connections to overall fitness, health and disease. 

PMID- 25999310
TI  - Characterization of substrate binding of the WW domains in human WWP2 protein.
AB  - WW domains harbor substrates containing proline-rich motifs, but the substrate
      specificity and binding mechanism remain elusive for those WW domains less
      amenable for structural studies, such as human WWP2 (hWWP2). Herein we have
      employed multiple techniques to investigate the second WW domain (WW2) in hWWP2.
      Our results show that hWWP2 is a specialized E3 for PPxY motif-containing
      substrates only and does not recognize other amino acids and phospho-residues.
      The strongest binding affinity of WW2, and the incompatibility between each WW
      domain, imply a novel relationship, and our SPR experiment reveals a dynamic
      binding mode in Class-I WW domains for the first time. The results from alanine
      scanning mutagenesis and modeling further point to functionally conserved
      residues in WW2. 

PMID- 25999312
TI  - Examining the impact of question surface features on students' answers to
      constructed-response questions on photosynthesis.
AB  - One challenge in science education assessment is that students often focus on
      surface features of questions rather than the underlying scientific principles.
      We investigated how student written responses to constructed-response questions
      about photosynthesis vary based on two surface features of the question: the
      species of plant and the order of two question prompts. We asked four versions of
      the question with different combinations of the two plant species and order of
      prompts in an introductory cell biology course. We found that there was not a
      significant difference in the content of student responses to versions of the
      question stem with different species or order of prompts, using both computerized
      lexical analysis and expert scoring. We conducted 20 face-to-face interviews with
      students to further probe the effects of question wording on student responses.
      During the interviews, we found that students thought that the plant species was
      neither relevant nor confusing when answering the question. Students identified
      the prompts as both relevant and confusing. However, this confusion was not
      specific to a single version. 

PMID- 25999311
TI  - Structural impact of complete CpG methylation within target DNA on specific
      complex formation of the inducible transcription factor Egr-1.
AB  - The inducible transcription factor Egr-1 binds specifically to 9-bp target
      sequences containing two CpG sites that can potentially be methylated at four
      cytosine bases. Although it appears that complete CpG methylation would make an
      unfavorable steric clash in the previous crystal structures of the complexes with
      unmethylated or partially methylated DNA, our affinity data suggest that DNA
      recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a
      1.4-A resolution, the crystal structure of the Egr-1 zinc-finger complex with
      completely methylated target DNA. Structural comparison of the three different
      methylation states reveals why Egr-1 can recognize the target sequences
      regardless of CpG methylation. 

PMID- 25999313
TI  - A model of how different biology experts explain molecular and cellular
      mechanisms.
AB  - Constructing explanations is an essential skill for all science learners. The
      goal of this project was to model the key components of expert explanation of
      molecular and cellular mechanisms. As such, we asked: What is an appropriate
      model of the components of explanation used by biology experts to explain
      molecular and cellular mechanisms? Do explanations made by experts from different
      biology subdisciplines at a university support the validity of this model? Guided
      by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an
      initial model was tested by asking seven biologists to explain a molecular
      mechanism of their choice. Data were collected from interviews, artifacts, and
      drawings, and then subjected to thematic analysis. We found that biologists
      explained the specific activities and organization of entities of the mechanism.
      In addition, they contextualized explanations according to their biological and
      social significance; integrated explanations with methods, instruments, and
      measurements; and used analogies and narrated stories. The derived methods,
      analogies, context, and how themes informed the development of our final MACH
      model of mechanistic explanations. Future research will test the potential of the
      MACH model as a guiding framework for instruction to enhance the quality of
      student explanations. 

PMID- 25999314
TI  - Test-enhanced learning: the potential for testing to promote greater learning in
      undergraduate science courses.
AB  - Testing within the science classroom is commonly used for both formative and
      summative assessment purposes to let the student and the instructor gauge
      progress toward learning goals. Research within cognitive science suggests,
      however, that testing can also be a learning event. We present summaries of
      studies that suggest that repeated retrieval can enhance long-term learning in a
      laboratory setting; various testing formats can promote learning; feedback
      enhances the benefits of testing; testing can potentiate further study; and
      benefits of testing are not limited to rote memory. Most of these studies were
      performed in a laboratory environment, so we also present summaries of
      experiments suggesting that the benefits of testing can extend to the classroom.
      Finally, we suggest opportunities that these observations raise for the classroom
      and for further research. 

PMID- 25999315
TI  - Analysis of r-protein and RNA conformation of 30S subunit intermediates in
      bacteria.
AB  - The ribosome is a large macromolecular complex that must be assembled efficiently
      and accurately for the viability of all organisms. In bacteria, this process must
      be robust and tunable to support life in diverse conditions from the ice of
      arctic glaciers to thermal hot springs. Assembly of the Small ribosomal SUbunit
      (SSU) of Escherichia coli has been extensively studied and is highly temperature
      dependent. However, a lack of data on SSU assembly for other bacteria is
      problematic given the importance of the ribosome in bacterial physiology. To
      broaden the understanding of how optimal growth temperature may affect SSU
      assembly, in vitro SSU assembly of two thermophilic bacteria, Geobacillus
      kaustophilus and Thermus thermophilus, was compared with that of E. coli. Using
      these phylogenetically, morphologically, and environmentally diverse bacteria, we
      show that SSU assembly is highly temperature-dependent and efficient SSU assembly
      occurs at different temperatures for each organism. Surprisingly, the assembly
      landscape is characterized by at least two distinct intermediate populations in
      the organisms tested. This novel, second intermediate, is formed in the presence
      of the full complement of r-proteins, unlike the previously observed RI* particle
      formed in the absence of late-binding r-proteins in E. coli. This work reveals
      multiple distinct intermediate populations are present during SSU assembly in
      vitro for several bacteria, yielding insights into RNP formation and possible
      antimicrobial development toward this common SSU target. 

PMID- 25999316
TI  - Multiple conformations are a conserved and regulatory feature of the RB1 5' UTR.
AB  - Folding to a well-defined conformation is essential for the function of
      structured ribonucleic acids (RNAs) like the ribosome and tRNA. Structured
      elements in the untranslated regions (UTRs) of specific messenger RNAs (mRNAs)
      are known to control expression. The importance of unstructured regions adopting
      multiple conformations, however, is still poorly understood. High-resolution
      SHAPE-directed Boltzmann suboptimal sampling of the Homo sapiens Retinoblastoma 1
      (RB1) 5' UTR yields three distinct conformations compatible with the experimental
      data. Private single nucleotide variants (SNVs) identified in two patients with
      retinoblastoma each collapse the structural ensemble to a single but distinct
      well-defined conformation. The RB1 5' UTRs from Bos taurus (cow) and Trichechus
      manatus latirostris (manatee) are divergent in sequence from H. sapiens (human)
      yet maintain structural compatibility with high-probability base pairs. SHAPE
      chemical probing of the cow and manatee RB1 5' UTRs reveals that they also adopt
      multiple conformations. Luciferase reporter assays reveal that 5' UTR mutations
      alter RB1 expression. In a traditional model of disease, causative SNVs disrupt a
      key structural element in the RNA. For the subset of patients with heritable
      retinoblastoma-associated SNVs in the RB1 5' UTR, the absence of multiple
      structures is likely causative of the cancer. Our data therefore suggest that
      selective pressure will favor multiple conformations in eukaryotic UTRs to
      regulate expression. 

PMID- 25999317
TI  - Systematic analysis of the Hmga2 3' UTR identifies many independent regulatory
      sequences and a novel interaction between distal sites.
AB  - The 3' untranslated regions (3' UTRs) of mRNAs regulate transcripts by serving as
      binding sites for regulatory factors, including microRNAs and RNA binding
      proteins. Binding of such trans-acting factors can control the rates of mRNA
      translation, decay, and other aspects of mRNA biology. To better understand the
      role of 3' UTRs in gene regulation, we performed a detailed analysis of a model
      mammalian 3' UTR, that of Hmga2, with the principal goals of identifying the
      complete set of regulatory elements within a single 3' UTR, and determining the
      extent to which elements interact with and affect one another. Hmga2 is an
      oncogene whose overexpression in cancers often stems from mutations that remove
      3'-UTR regulatory sequences. We used reporter assays in cultured cells to
      generate maps of cis-regulatory information across the Hmga2 3' UTR at different
      resolutions, ranging from 50 to 400 nt. We found many previously unidentified
      regulatory sites, a large number of which were up-regulating. Importantly, the
      overall location and impact of regulatory sites was conserved between different
      species (mouse, human, and chicken). By systematically comparing the regulatory
      impact of 3'-UTR segments of different sizes we were able to determine that the
      majority of regulatory sequences function independently; only a very small number
      of segments showed evidence of any interactions. However, we discovered a novel
      interaction whereby terminal 3'-UTR sequences induced internal up-regulating
      elements to convert to repressive elements. By fully characterizing one 3' UTR,
      we hope to better understand the principles of 3'-UTR-mediated gene regulation. 

PMID- 25999318
TI  - Sequence-controlled RNA self-processing: computational design, biochemical
      analysis, and visualization by AFM.
AB  - Reversible chemistry allowing for assembly and disassembly of molecular entities
      is important for biological self-organization. Thus, ribozymes that support both
      cleavage and formation of phosphodiester bonds may have contributed to the
      emergence of functional diversity and increasing complexity of regulatory RNAs in
      early life. We have previously engineered a variant of the hairpin ribozyme that
      shows how ribozymes may have circularized or extended their own length by forming
      concatemers. Using the Vienna RNA package, we now optimized this hairpin ribozyme
      variant and selected four different RNA sequences that were expected to
      circularize more efficiently or form longer concatemers upon transcription. (Two
      dimensional) PAGE analysis confirms that (i) all four selected ribozymes are
      catalytically active and (ii) high yields of cyclic species are obtained. AFM
      imaging in combination with RNA structure prediction enabled us to calculate the
      distributions of monomers and self-concatenated dimers and trimers. Our results
      show that computationally optimized molecules do form reasonable amounts of
      trimers, which has not been observed for the original system so far, and we
      demonstrate that the combination of theoretical prediction, biochemical and
      physical analysis is a promising approach toward accurate prediction of ribozyme
      behavior and design of ribozymes with predefined functions. 

PMID- 25999319
TI  - Claudin-related intestinal diseases.
AB  - With up to 200 m(2) the human intestine is the organ with the largest absorptive
      surface of the body. It is lined by a single layer of epithelial cells that
      separates the host from the environment. The intestinal epithelium provides both,
      selective absorption of nutrients, ions, and water but also a highly effective
      barrier function which includes the first line of defense against environmental
      antigens. The paracellular part of this barrier function is provided by tight
      junction (TJ) proteins, especially the large family of claudins. Changes in
      abundance or molecular structure of claudins can generally result in three
      typical effects, (i) decreased absorptive passage, (ii) increased secretory
      passage of small solutes and water causing leak flux diarrhea and (iii) increased
      absorptive passage of macromolecules which may induce inflammatory processes.
      Several intestinal diseases are associated with such changes that can result in
      intestinal inflammation and symptoms like weight loss, abdominal pain or
      diarrhea. This review summarizes our current knowledge on barrier dysfunction and
      claudin dysregulation in several intestinal diseases gastroenterologists are
      often faced with, like inflammatory bowel disease, microscopic colitis, celiac
      disease, irritable bowel syndrome, gallstones and infectious diseases like HIV
      enteropathy, Campylobacter jejuni and Clostridium perfringens infection.

PMID- 25999320
TI  - Formation of the vertebrate embryo: Moving beyond the Spemann organizer.
AB  - During the course of their classic experiments, Hilde Mangold and Hans Spemann
      discovered that the dorsal blastopore lip of an amphibian gastrula was able to
      induce formation of a complete embryonic axis when transplanted into the ventral
      side of a host gastrula embryo. Since then, the inducing activity of the dorsal
      lip has been known as the Spemann or dorsal organizer. During the past 25 years,
      studies performed in a variety of species have led to the identification of
      molecular factors associated with the properties of this tissue. However, none of
      them is, by itself, able to induce formation of the main body axis from a
      population of naive pluripotent embryonic cells. Recently, experiments performed
      using the zebrafish (Danio rerio) revealed that the organizing activities present
      in the embryo are not restricted to the Spemann organizer but are distributed
      along the entire blastula/gastrula margin. These organizing activities result
      from the interaction between two opposing gradients of morphogens, BMP and Nodal,
      that are the primary signals that trigger the cascade of developmental events
      leading to the organization of the embryo. These studies mark the end of the era
      during which developmental biologists saw the Spemann organizer as the core
      element for the organization of the vertebrate embryonic axis and, instead,
      provides opportunities for the experimental control of morphogenesis starting
      with a population of embryonic pluripotent cells that will be instructed using
      those two morphogen gradients. 

PMID- 25999321
TI  - Predictors of Agreement With Writing Advance Directives Among Older Korean
      Adults.
AB  - PURPOSE: To determine the predictors of agreement with writing advance directives
      (ADs) among older Korean adults. DESIGN: This was a secondary analysis of a study
      that compared the differences in knowledge, experience, and preference about ADs
      between community and facility-dwelling older adults. Data were collected through
      self-reported questionnaires. In this study, after 25 cases were excluded from
      the original sample (N = 181) for incomplete data, a sample of 156 was analyzed
      using multiple logistic regression analysis. RESULTS: Older adults' experiences
      with having thought about life-sustaining treatments, odds ratio (OR) = 4.02, 95%
      confidence interval (CI) [1.56, 10.38], agreements with legalization of ADs, OR =
      4.68, 95% CI [1.69, 12.96], and wishes to obtain information about medical
      status, OR = 3.78, 95% CI [1.66, 8.64], were identified as the predictors of
      agreement with writing ADs. IMPLICATIONS FOR PRACTICE: Discussion channels and
      educational programs about ADs should be developed for older Korean adults.

PMID- 25999322
TI  - Using Community-Based Participatory Research to Investigate Meaningful Prenatal
      Care Among African American Women.
AB  - PURPOSE: In the United States, African American babies die more than twice as
      often as White babies. The cause for this difference remains elusive, yet is
      likely complex with one factor being inadequate cultural care of pregnant African
      American women. The purpose of this study was to explore African American women's
      perspectives of meaningful prenatal care. DESIGN: Community-based participatory
      research was employed for this study using photovoice. The sample included 11
      African American mothers in an urban community in Midwestern United States.
      FINDINGS: Five themes were abstracted from the data: (1) Access to Care; (2) Soul
      Nourishment; (3) Companionship; (4) Help Me, Teach Me; and (5) The Future.
      DISCUSSION/CONCLUSION: Meaningful prenatal care is influenced by culture. African
      American women need physical, social, and soulful support to enhance
      meaningfulness of care during pregnancy. PRACTICE IMPLICATIONS: The findings
      support that meaningfulness of prenatal care for African American women may be
      enhanced by accessible and uniquely designed, culturally congruent models of
      prenatal care.

PMID- 25999323
TI  - Factors Affecting Professional Autonomy of Japanese Nurses Caring for Culturally
      and Linguistically Diverse Patients in a Hospital Setting in Japan.
AB  - PURPOSE: The study aimed to analyze the professional autonomy of Japanese nurses
      when caring for non-Japanese patients and to identify its contributing factors.
      METHOD: A descriptive cross-sectional design was used. Participants included 238
      clinical nurses working at 27 hospitals in Japan. The Intercultural Sensitivity
      Scale (Chen and Starosta), and the Scale for Professional Autonomy in Nursing
      (Kikuchi and Harada) were used to measure intercultural sensitivity and
      professional autonomy. Stepwise multiple regression analysis was used to identify
      the most significant factors affecting professional autonomy. RESULTS:
      Professional autonomy of Japanese nurses caring for non-Japanese patients was
      significantly lower than when caring for Japanese patients (142.84 vs. 172.85; p
      < .001). Contributing factors were intercultural sensitivity (p < .001), length
      of nurse experience (p < .05), and availability of interpretation service (p <
      .05). CONCLUSION: Incorporating transcultural nursing content into training
      programs in schools and hospitals could enhance professional autonomy of Japanese
      nurses by promoting intercultural sensitivity.

PMID- 25999325
TI  - Variability in Human Bitter Taste Sensitivity to Chemically Diverse Compounds Can
      Be Accounted for by Differential TAS2R Activation.
AB  - The human population displays high variation in taste perception. Differences in
      individual taste sensitivity may also impact on nutrient intake and overall
      appetite. A well-characterized example is the variable perception of bitter
      compounds such as 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC),
      which can be accounted for at the molecular level by polymorphic variants in the
      specific type 2 taste receptor (TAS2R38). This phenotypic variation has been
      associated with influencing dietary preference and other behaviors, although the
      generalization of PROP/PTC taster status as a predictor of sensitivity to other
      tastes is controversial. Here, we proposed that the taste sensitivities of
      different bitter compounds would be correlated only when they activate the same
      bitter taste receptor. Thirty-four volunteers were exposed to 8 bitter compounds
      that were selected based on their potential to activate overlapping and distinct
      repertoires of TAS2Rs. Taste intensity ratings were evaluated using the general
      Labeled Magnitude Scale. Our data demonstrate a strong interaction between the
      intensity for bitter substances when they activate common TAS2Rs. Consequently,
      PROP/PTC sensitivity was not a reliable predictor of general bitter sensitivity.
      In addition, our findings provide a novel framework to predict taste sensitivity
      based on their specific T2R activation profile. 

PMID- 25999324
TI  - Dspp-independent Effects of Transgenic Trps1 Overexpression on Dentin Formation.
AB  - The Trps1 transcription factor is highly expressed in dental mesenchyme and
      preodontoblasts, while in mature, secretory odontoblasts, it is expressed at low
      levels. Previously, we have shown that high Trps1 levels in mature odontoblasts
      impair their function in vitro and in vivo. Col1a1-Trps1 transgenic (Trps1-Tg)
      mice demonstrate defective dentin secretion and mineralization, which are
      associated with significantly decreased Dspp expression due to direct repression
      of the Dspp gene by Trps1. Here, by crossing Trps1-Tg and Col1a1-Dspp transgenic
      (Dspp-Tg) mice, we generated Col1a1-Trps1;Col1a1-Dspp double transgenic (double
      Tg) mice in which Dspp was restored in odontoblasts overexpressing Trps1.
      Comparative micro-computed tomography analyses revealed partial correction of the
      dentin volume and no improvement of dentin mineralization in double transgenic
      mice in comparison with Trps1-Tg and wild-type (WT) mice. In addition, dentin of
      double-Tg mice has an irregular mineralization pattern characteristic for dentin
      in hypophosphatemic rickets. Consistent with this phenotype, decreased levels of
      Phex, Vdr, and Fam20c proteins are detected in both Trps1-Tg and double-Tg
      odontoblasts in comparison with WT and Dspp-Tg odontoblasts. This suggests that
      the Dspp-independent dentin mineralization defects in Trps1-Tg mice are a result
      of downregulation of a group of proteins critical for mineral deposition within
      the dentin matrix. In summary, by demonstrating that Trps1 functions as a
      repressor of later stages of dentinogenesis, we provide functional significance
      of the dynamic Trps1 expression pattern during dentinogenesis. 

PMID- 25999326
TI  - Meconium aspiration syndrome in infants of HIV-positive women: a case-control
      study.
AB  - OBJECTIVE: Our aim was to determine whether maternal HIV infection in the current
      era is associated with an increased incidence of meconium aspiration syndrome
      (MAS) in their infants. METHODS: Infants born to 149 HIV-positive women at our
      hospital over a 5-year period were compared with infants born to HIV-negative
      women in a retrospective case-control study. Charts of all 298 patients included
      in the study were reviewed for maternal and infant demographics, HIV treatment,
      vertical transmission and untoward events at delivery or during the hospital
      course. RESULTS: When compared with HIV-negative women, a greater proportion of
      HIV-positive women had meconium-stained amniotic fluid (MSAF), 33% vs. 13%,
      P<0.001; and thick MSAF, 17% vs. 5%, P<0.001, respectively. Seven of 298 infants
      were admitted to the neonatal intensive care unit for MAS; all seven were born to
      HIV-positive women (P=0.015). Although in utero exposure to illicit drugs is a
      reported risk factor for meconium staining of the amniotic fluid and such drug
      exposure was more common among our HIV-positive sample, controlling for this and
      other possible covariates did not greatly reduce the association of HIV status
      with meconium-related complications of delivery. CONCLUSIONS: Infants born to HIV
      positive women had significantly more MSAF and MAS than infants born to non
      infected women. It is unclear whether this association results from maternal HIV
      infection itself or from anti-retroviral therapy. Maternal and infant care
      providers should be prepared for this complication when attending to the
      deliveries of HIV-positive women.

PMID- 25999327
TI  - Effects of GnRH analogue treatment on anterior pituitary hormones in children
      with central precocious puberty.
AB  - INTRODUCTION AND PURPOSE: This study aims to investigate the effect of
      Gonadotropin-releasing hormone analogues (GnRHa) treatment on anterior pituitary
      hormones in female children with central precocious puberty (CPP). SUBJECTS AND
      METHOD: There were 62 female children who had been diagnosed with CPP and
      received GnRHa (Leuprolide acetate, 3.75 mg intramuscular/subcutaneous/28 days)
      included in the study. All subjects were clinically evaluated prior to treatment
      and every 3 months during treatment with serum LH, FSH, ACTH, TSH, PRL as
      pituitary hormones, and the end hormones such as plasma E2, cortisol, fT3, fT4
      levels were measured. IGF-1 and IGFBP-3 levels were measured, and SDS was
      evaluated according to age and gender. RESULTS: Prolactin levels were higher
      during GnRHa treatment compared to pre-treatment values although the increase was
      statistically significant only at month 3. In addition, while 2 (3.2%) of the
      patients had hyperprolactinemia before treatment, 11 (17.7%) patients developed
      hyperprolactinemia at different time points during treatment. CONCLUSION: This
      study concluded that GnRHa treatment resulted in hyperprolactinemia and had no
      significant effect other pituitary hormones.

PMID- 25999328
TI  - Biosynthesis of membrane dependent proteins in insect cell lysates:
      identification of limiting parameters for folding and processing.
AB  - G protein-coupled receptors, like many other membrane proteins, are notoriously
      difficult to synthesize in conventional cellular systems. Although expression in
      insect cells is considered the preferred technique for structural
      characterizations in particular, inefficient membrane translocation, instability,
      toxic effects and low yields still pose clear limitations for their production in
      living cells. Recent studies started to explore alternative strategies for the in
      vitro production of problematic membrane proteins in cell-free lysates in
      combination with supplied membranes. We provide a detailed study on the
      production efficiencies and quality of G protein-coupled receptors, Fab fragments
      and other proteins synthesized in insect cell lysates containing endogenous
      microsomes. Effects of different reaction kinetics, redox conditions and sample
      preparations on the specific activities of synthesized proteins have been
      analyzed. The extent of glycosylation, membrane translocation and percentages of
      ligand binding active fractions of synthesized protein samples have been
      determined. We provide strong evidence that membrane insertion of integral
      membrane proteins can represent a prime limiting factor for their preparative
      scale in vitro production. Improved expression protocols resulting into higher
      production rates yielded more active protein in case of Fab fragments, but not in
      case of the human endothelin B receptor. 

PMID- 25999329
TI  - Outcomes in HIV/HBV-Coinfected Patients in the Tenofovir Era Are Greatly Affected
      by Immune Suppression.
AB  - OBJECTIVES: HIV-infected patients have higher mortality when coinfected with
      hepatitis B virus (HBV). With potent highly active antiretroviral therapy (HAART)
      and the use of tenofovir (TDF), outcomes may improve. Our objective was to
      determine the clinical and virological outcomes of a HIV/HBV-Coinfected cohort at
      our center since TDF became available. METHODS: We retrospectively studied all
      HIV/HBV-Coinfected adults followed between 2002 and 2012 for >=3 months. Outcome
      measurements included HBV DNA suppression, HBV e-antigen (HBeAg) and HBV surface
      antigen (HBsAg) clearance, cirrhosis diagnosis, development of liver
      complications, and overall and liver-related mortality. Predicting factors were
      assessed with log-rank test and logistic regression. RESULTS: Median time to
      follow-up of the 99 patients included was 5 years. Undetectable HBV DNA and HBsAg
      loss were achieved by 65% and 18%, respectively. Overall and liver-related
      mortality rates were 4.58 and 0.91 per 100 person-years, respectively. Most
      patients died of causes unrelated to the liver. Four patients died from
      hepatocellular carcinoma (HCC) and one, hepatitis C virus (HCV) coinfected, from
      liver failure. Higher CD4 counts at last follow-up were associated with HBV
      suppression (odds ratio [OR] 1.004, 95% confidence interval [CI] 1.001-1.006,
      P=.007), HBeAg loss (OR 1.003, 95% CI 1-1.005, P=.02), HBsAg loss (CD4 count>700
      cells/mm3, OR 3.80, 95% CI 1.06-13.58, P=.04), and survival (OR .994, 95% CI
      0.990-0.997, P<.0001). HCV coinfection was associated with higher overall
      mortality (OR 7.74, 95% CI 1.47-40.81, P=.02). CONCLUSION: Mortality was high and
      most often unrelated to liver disease in this HIV/HBV-Coinfected cohort treated
      predominantly with TDF-containing HAART. Optimal CD4 counts predicted survival
      and the achievement of HBV virological end points. Tenofovir prevented liver
      decompensation but not HCC, which was the predominant cause of liver death.

PMID- 25999330
TI  - Unknown HIV Status in the Emergency Department: Implications for Expanded Testing
      Strategies.
AB  - OBJECTIVES: The authors sought to determine the prevalence of unknown HIV status
      among emergency department (ED) patients, how it has changed over time, and
      whether it differs according to patient characteristics. METHODS: The authors
      used electronic medical record data to identify whether HIV status was known or
      unknown among patients aged >=13 seen in the ED of a large, urban medical center
      between 2006 and 2011. The authors used multivariate logistic regression to
      identify the characteristics associated with unknown HIV status. RESULTS: The
      prevalence of unknown HIV status decreased each year, from 87.7% in 2006 to 74.9%
      in 2011 (P < .001). Characteristics associated with unknown HIV status included
      being nonblack, in the youngest and oldest age-groups, and nonpublically insured.
      Compared to men, women without prior pregnancy were equally likely to have
      unknown HIV status, but women with prior pregnancy were significantly less likely
      to have unknown HIV status. CONCLUSION: The prevalence of unknown HIV status is
      decreasing, but in 2011 75% of ED patients aged >=13 still had unknown status,
      and it was associated with specific patient characteristics. Understanding the
      trends in the prevalence of unknown HIV status and how it is associated with
      patient characteristics should inform the design and implementation of expanded
      HIV-testing strategies.

PMID- 25999331
TI  - The overview of the radon and environmental characteristics measurements in the
      Czech show caves.
AB  - This paper focuses on the measurement and assessment of absorbed doses of
      radiation in caves of the Czech Republic, some of which exhibit high activity
      concentration of radon in air. Presented is an analysis and recommendations based
      on measurement results obtained in the underground caves over the past 12 y. The
      most important results for cave environments were as follows: integral radon
      monitoring using RAMARN detectors can provide more consistent results for
      calculating the effective dose; no major differences were shown in the average
      radon activity concentration during working time as opposed to non-working time;
      the unattached fraction of radioactive particles in air ranged from 0.03 to 0.6,
      with arithmetical average fp = 0.13; the direct dependence between equilibrium
      factor F and the size of the unattached fraction fp was described using the Log
      Power expression ln(1/fp) = a*ln(1/F)(b); the calculated values for coefficients
      a and b were 1.85 and -1.096, respectively. The individual cave factor for each
      investigated underground area was calculated. 

PMID- 25999332
TI  - Internal dosimetry for intake of 18FDG using spot urine sample.
AB  - In nuclear medicine, workers handle unsealed radioactive materials. Among the
      materials, (18)FDG is the most widely used in PET/CT technique. Because of the
      short half-life of (18)F, it is very challenging to monitor internal exposure of
      nuclear medicine workers using in vitro bioassay. Thus, the authors developed the
      new in vitro bioassay methodology for short half-life nuclides. In the
      methodology, spot urine sample is directly used without normalisation to 1-d
      urine sample and the spot urinary excretion function was newly proposed. In order
      to estimate the intake and committed dose for workers dealing (18)FDG, biokinetic
      models for FDG was also developed. Using the new methodology and biokinetic
      model, the in vitro bioassay for workers dealing (18)FDG was successfully
      performed. The authors expect that this methodology will be very useful for
      internal monitoring of workers who deal short-lived radionuclides in the all
      field as well as the nuclear medicine field. 

PMID- 25999333
TI  - Design and functionalities of the MADOR(r) software suite for dose-reduction
      management after DTPA therapy.
AB  - A software suite on biokinetics of radionuclides and internal dosimetry intended
      for the occupational health practitioners of nuclear industry and for expert
      opinions has been developed under Borland C++ BuilderTM. These computing tools
      allow physicians to improve the dosimetric follow-up of workers in agreement with
      the French regulations and to manage new internal contaminations by radionuclides
      such as Pu and/or Am after diethylene triamine penta-acetic acid treatments. In
      this paper, the concept and functionalities of the first two computing tools of
      this MADOR((r)) suite are described. The release 0.0 is the forensic application,
      which allows calculating the derived recording levels for intake by inhalation or
      ingestion of the main radioisotopes encountered in occupational environment.
      Indeed, these reference values of activity are convenient to interpret rapidly
      the bioassay measurements and make decisions as part of medical monitoring. The
      release 1.0 addresses the effect of DTPA treatments on Pu/Am biokinetics and the
      dose benefit. The forensic results of the MADOR((r)) suite were validated by
      comparison with reference data. 

PMID- 25999334
TI  - Transference-focused psychotherapy for borderline personality disorder: change in
      reflective function.
AB  - Borderline personality disorder is associated with deficits in personality
      functioning and mentalisation. In a randomised controlled trial 104 people with
      borderline personality disorder received either transference-focused
      psychotherapy (TFP) or treatment by experienced community therapists. Among other
      outcome variables, mentalisation was assessed by means of the Reflective
      Functioning Scale (RF Scale). Findings revealed only significant improvements in
      reflective function in the TFP group within 1 year of treatment. The between
      group effect was of medium size (d = 0.45). Improvements in reflective function
      were significantly correlated with improvements in personality organisation. 

PMID- 25999335
TI  - Agomelatine or placebo as adjunctive therapy to a mood stabiliser in bipolar I
      depression: randomised double-blind placebo-controlled trial.
AB  - BACKGROUND: Adjunctive antidepressant therapy is commonly used to treat acute
      bipolar depression but few studies have examined this strategy. AIMS: To examine
      the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in
      bipolar depression. METHOD: Patients who were currently depressed despite taking
      lithium or valproate for at least 6 weeks were randomised to treatment with
      agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44
      weeks of continuation therapy (trial registration: ISRCTN28588282). RESULTS: No
      significant differences in improvement of depressive symptoms were observed
      between the two groups either at 8 weeks or 52 weeks on the primary efficacy
      measure of change in Montgomery-Asberg Depression Rating Scale scores from
      baseline to end-point. Adverse events including switches into mania/hypomania
      were low and similar in both groups. CONCLUSIONS: Agomelatine adjunctive therapy
      was not superior to placebo adjunctive therapy for acute bipolar depression.

PMID- 25999336
TI  - Layers of listening: qualitative analysis of the impact of early intervention
      services for first-episode psychosis on carers' experiences.
AB  - BACKGROUND: Early intervention services (EIS) comprise low-stigma, youth-friendly
      mental health teams for young people undergoing first-episode psychosis (FEP).
      Engaging with the family of the young person is central to EIS policy and
      practice.AimsBy analysing carers' accounts of their daily lives and affective
      challenges during a relative's FEP against the background of wider research into
      EIS, this paper explores relationships between carers' experiences and EIS.
      METHOD: Semi-structured longitudinal interviews with 80 carers of young people
      with FEP treated through English EIS. RESULTS: Our data suggest that EIS
      successfully aid carers to support their relatives, particularly through the
      provision of knowledge about psychosis and medications. However, paradoxical
      ramifications of these user-focused engagements also emerge; they risk leaving
      carers' emotions unacknowledged and compounding an existing lack of help-seeking.
      CONCLUSIONS: By focusing on EIS's engagements with carers, this paper draws
      attention to an urgent broader question: as a continuing emphasis on care outside
      the clinic space places family members at the heart of the care of those with
      severe mental illness, we ask: who can, and should, support carers, and in what
      ways?

PMID- 25999337
TI  - Components of therapy as mechanisms of change in cognitive therapy for people at
      risk of psychosis: analysis of the EDIE-2 trial.
AB  - BACKGROUND: Research suggests that the way in which cognitive therapy is
      delivered is an important factor in determining outcomes. We test the hypotheses
      in which the development of a shared problem list, use of case formulation,
      homework tasks and active intervention strategies will act as process variables.
      METHOD: Presence of these components during therapy is taken from therapist
      notes. The direct and indirect effect of the intervention is estimated by an
      instrumental variable analysis. RESULTS: A significant decrease in the symptom
      score for case formulation (coefficient = -23, 95% CI -44 to -1.7, P = 0.036) and
      homework (coefficient = -0.26, 95% CI -0.51 to -0.001, P = 0.049) is found.
      Improvement with the inclusion of active change strategies is of borderline
      significance (coefficient = -0.23, 95% CI -0.47 to 0.005, P = 0.056).
      CONCLUSIONS: There is a greater treatment effect if formulation and homework are
      involved in therapy. However, high correlation between components means that
      these may be indicators of overall treatment fidelity.

PMID- 25999338
TI  - Hedonic and disgust taste perception in borderline personality disorder and
      depression.
AB  - Depression and borderline personality disorder (BPD) are both thought to be
      accompanied by alterations in the subjective experience of environmental rewards.
      We evaluated responses in women to sweet, bitter and neutral tastes (juice,
      quinine and water): 29 with depression, 17 with BPD and 27 healthy controls. The
      BPD group gave lower pleasantness and higher disgust ratings for quinine and
      juice compared with the control group; the depression group did not differ
      significantly from the control group. Juice disgust ratings were related to self
      disgust in BPD, suggesting close links between abnormal sensory processing and
      self-identity in BPD. 

PMID- 25999339
TI  - Reciprocal associations between smoking cessation and depression in older
      smokers: findings from the English Longitudinal Study of Ageing.
AB  - BACKGROUND: Depression is a particular problem in older people and it is
      important to know how it affects and is affected by smoking cessation. AIMS: To
      identify reciprocal, longitudinal relationships between smoking cessation and
      depression among older smokers. METHOD: Across four waves, covering six years
      (2002-2008), changes in smoking status and depression, measured using the 8-item
      Centre for Epidemiologic Studies Depression Scale, were assessed among recent ex
      smokers and smokers (n = 2375) in the English Longitudinal Study of Ageing.
      RESULTS: In latent growth curve analysis, smoking at baseline predicted
      depression caseness longitudinally and vice versa. When both processes were
      modelled concurrently, depression predicted continued smoking longitudinally
      (B(beta) = 0.21 (0.27); 95% CI = 0.08-0.35) but not the other way round. This was
      the case irrespective of mental health history and adjusting for a range of
      covariates. CONCLUSIONS: In older smokers, depression appears to act as an
      important barrier to quitting, although quitting has no long-term impact on
      depression.

PMID- 25999340
TI  - Novel mechanism of gene regulation: the protein Rv1222 of Mycobacterium
      tuberculosis inhibits transcription by anchoring the RNA polymerase onto DNA.
AB  - We propose a novel mechanism of gene regulation in Mycobacterium tuberculosis
      where the protein Rv1222 inhibits transcription by anchoring RNA polymerase
      (RNAP) onto DNA. In contrast to our existing knowledge that transcriptional
      repressors function either by binding to DNA at specific sequences or by binding
      to RNAP, we show that Rv1222-mediated transcription inhibition requires
      simultaneous binding of the protein to both RNAP and DNA. We demonstrate that the
      positively charged C-terminus tail of Rv1222 is responsible for anchoring RNAP on
      DNA, hence the protein slows down the movement of RNAP along the DNA during
      transcription elongation. The interaction between Rv1222 and DNA is
      electrostatic, thus the protein could inhibit transcription from any gene. As
      Rv1222 slows down the RNA synthesis, upon expression of the protein in
      Mycobacterium smegmatis or Escherichia coli, the growth rate of the bacteria is
      severely impaired. The protein does not possess any significant affinity for DNA
      polymerase, thus, is unable to inhibit DNA synthesis. The proposed mechanism by
      which Rv1222 inhibits transcription reveals a new repertoire of prokaryotic gene
      regulation. 

PMID- 25999341
TI  - DNA-PKcs phosphorylates hnRNP-A1 to facilitate the RPA-to-POT1 switch and
      telomere capping after replication.
AB  - The heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) has been implicated in
      telomere protection and telomerase activation. Recent evidence has further
      demonstrated that hnRNP-A1 plays a crucial role in maintaining newly replicated
      telomeric 3' overhangs and facilitating the switch from replication protein A
      (RPA) to protection of telomeres 1 (POT1). The role of hnRNP-A1 in telomere
      protection also involves DNA-dependent protein kinase catalytic subunit (DNA
      PKcs), although the detailed regulation mechanism has not been clear. Here we
      report that hnRNP-A1 is phosphorylated by DNA-PKcs during the G2 and M phases and
      that DNA-PK-dependent hnRNP-A1 phosphorylation promotes the RPA-to-POT1 switch on
      telomeric single-stranded 3' overhangs. Consequently, in cells lacking hnRNP-A1
      or DNA-PKcs-dependent hnRNP-A1 phosphorylation, impairment of the RPA-to-POT1
      switch results in DNA damage response at telomeres during mitosis as well as
      induction of fragile telomeres. Taken together, our results indicate that DNA
      PKcs-dependent hnRNP-A1 phosphorylation is critical for capping of the newly
      replicated telomeres and prevention of telomeric aberrations. 

PMID- 25999342
TI  - Characterization of human herpesvirus 6A/B U94 as ATPase, helicase, exonuclease
      and DNA-binding proteins.
AB  - Human herpesvirus-6A (HHV-6A) and HHV-6B integrate their genomes into the
      telomeres of human chromosomes, however, the mechanisms leading to integration
      remain unknown. HHV-6A/B encode a protein that has been proposed to be involved
      in integration termed U94, an ortholog of adeno-associated virus type 2 (AAV-2)
      Rep68 integrase. In this report, we addressed whether purified recombinant
      maltose-binding protein (MBP)-U94 fusion proteins of HHV-6A/B possess biological
      functions compatible with viral integration. We could demonstrate that MBP-U94
      efficiently binds both dsDNA and ssDNA containing telomeric repeats using gel
      shift assay and surface plasmon resonance. MBP-U94 is also able to hydrolyze
      adenosine triphosphate (ATP) to ADP, providing the energy for further catalytic
      activities. In addition, U94 displays a 3' to 5' exonuclease activity on dsDNA
      with a preference for 3'-recessed ends. Once the DNA strand reaches 8-10 nt in
      length, the enzyme dissociates it from the complementary strand. Lastly, MBP-U94
      compromises the integrity of a synthetic telomeric D-loop through exonuclease
      attack at the 3' end of the invading strand. The preferential DNA binding of MBP
      U94 to telomeric sequences, its ability to hydrolyze ATP and its
      exonuclease/helicase activities suggest that U94 possesses all functions required
      for HHV-6A/B chromosomal integration. 

PMID- 25999343
TI  - Stereospecific suppression of active site mutants by methylphosphonate
      substituted substrates reveals the stereochemical course of site-specific DNA
      recombination.
AB  - Tyrosine site-specific recombinases, which promote one class of biologically
      important phosphoryl transfer reactions in DNA, exemplify active site mechanisms
      for stabilizing the phosphate transition state. A highly conserved arginine duo
      (Arg-I; Arg-II) of the recombinase active site plays a crucial role in this
      function. Cre and Flp recombinase mutants lacking either arginine can be rescued
      by compensatory charge neutralization of the scissile phosphate via
      methylphosphonate (MeP) modification. The chemical chirality of MeP, in
      conjunction with mutant recombinases, reveals the stereochemical contributions of
      Arg-I and Arg-II. The SP preference of the native reaction is specified primarily
      by Arg-I. MeP reaction supported by Arg-II is nearly bias-free or RP-biased,
      depending on the Arg-I substituent. Positional conservation of the arginines does
      not translate into strict functional conservation. Charge reversal by glutamic
      acid substitution at Arg-I or Arg-II has opposite effects on Cre and Flp in MeP
      reactions. In Flp, the base immediately 5' to the scissile MeP strongly
      influences the choice between the catalytic tyrosine and water as the nucleophile
      for strand scission, thus between productive recombination and futile hydrolysis.
      The recombinase active site embodies the evolutionary optimization of
      interactions that not only favor the normal reaction but also proscribe
      antithetical side reactions. 

PMID- 25999344
TI  - TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization.
AB  - The ends of eukaryotic chromosomes need to be protected from the activation of a
      DNA damage response that leads the cell to replicative senescence or apoptosis.
      In mammals, protection is accomplished by a six-factor complex named shelterin,
      which organizes the terminal TTAGGG repeats in a still ill-defined structure, the
      telomere. The stable interaction of shelterin with telomeres mainly depends on
      the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric
      repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment
      characterized by a very compact nucleosomal organization. In this work we show
      that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone
      octamer. By means of in vitro models, we found that TRF2 binding is strongly
      hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently
      to telomeric DNA in a nucleosomal context and is able to remodel telomeric
      nucleosomal arrays. Our results indicate that the different behavior of TRF
      proteins partly depends on the interaction with histone tails of their divergent
      N-terminal domains. We propose that the interplay between the histone octamer and
      TRF proteins plays a role in the steps leading to telomere deprotection. 

PMID- 25999345
TI  - Primerize: automated primer assembly for transcribing non-coding RNA domains.
AB  - Customized RNA synthesis is in demand for biological and biotechnological
      research. While chemical synthesis and gel or chromatographic purification of RNA
      is costly and difficult for sequences longer than tens of nucleotides, a pipeline
      of primer assembly of DNA templates, in vitro transcription by T7 RNA polymerase
      and kit-based purification provides a cost-effective and fast alternative for
      preparing RNA molecules. Nevertheless, designing template primers that optimize
      cost and avoid mispriming during polymerase chain reaction currently requires
      expert inspection, downloading specialized software or both. Online servers are
      currently not available or maintained for the task. We report here a server named
      Primerize that makes available an efficient algorithm for primer design developed
      and experimentally tested in our laboratory for RNA domains with lengths up to
      300 nucleotides. Free access: http://primerize.stanford.edu. 

PMID- 25999346
TI  - ATP-dependent motor activity of the transcription termination factor Rho from
      Mycobacterium tuberculosis.
AB  - The bacterial transcription termination factor Rho-a ring-shaped molecular motor
      displaying directional, ATP-dependent RNA helicase/translocase activity-is an
      interesting therapeutic target. Recently, Rho from Mycobacterium tuberculosis
      (MtbRho) has been proposed to operate by a mechanism uncoupled from molecular
      motor action, suggesting that the manner used by Rho to dissociate
      transcriptional complexes is not conserved throughout the bacterial kingdom.
      Here, however, we demonstrate that MtbRho is a bona fide molecular motor and
      directional helicase which requires a catalytic site competent for ATP hydrolysis
      to disrupt RNA duplexes or transcription elongation complexes. Moreover, we show
      that idiosyncratic features of the MtbRho enzyme are conferred by a large,
      hydrophilic insertion in its N-terminal 'RNA binding' domain and by a non
      canonical R-loop residue in its C-terminal 'motor' domain. We also show that the
      'motor' domain of MtbRho has a low apparent affinity for the Rho inhibitor
      bicyclomycin, thereby contributing to explain why M. tuberculosis is resistant to
      this drug. Overall, our findings support that, in spite of adjustments of the Rho
      motor to specific traits of its hosting bacterium, the basic principles of Rho
      action are conserved across species and could thus constitute pertinent screening
      criteria in high-throughput searches of new Rho inhibitors. 

PMID- 25999347
TI  - Modulation of LSD1 phosphorylation by CK2/WIP1 regulates RNF168-dependent 53BP1
      recruitment in response to DNA damage.
AB  - Proper DNA damage response is essential for the maintenance of genome integrity.
      The E3 ligase RNF168 deficiency fully prevents both the initial recruitment and
      retention of 53BP1 at sites of DNA damage. In response to DNA damage, RNF168
      dependent recruitment of the lysine-specific demethylase LSD1 to the site of DNA
      damage promotes local H3K4me2 demethylation and ubiquitination of H2A/H2AX,
      facilitating 53BP1 recruitment to sites of DNA damage. Alternatively, RNF168
      mediated K63-linked ubiquitylation of 53BP1 is required for the initial
      recruitment of 53BP1 to sites of DNA damage and for its function in repair. We
      demonstrated here that phosphorylation and dephosphorylation of LSD1 at S131 and
      S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase
      1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other
      directly. CK2-mediated phosphorylation of LSD1 exhibited no impact on its
      interaction with 53BP1, but promoted its interaction with RNF168 and RNF168
      dependent 53BP1 ubiquitination and subsequent recruitment to the DNA damage
      sites. Furthermore, overexpression of phosphorylation-defective mutants failed to
      restore LSD1 depletion-induced cellular sensitivity to DNA damage. Taken
      together, our results suggest that LSD1 phosphorylation modulated by CK2/WIP1
      regulates RNF168-dependent 53BP1 recruitment directly in response to DNA damage
      and cellular sensitivity to DNA damaging agents. 

PMID- 25999348
TI  - Gene expression in "young adult type" breast cancer: a retrospective analysis.
AB  - BACKGROUND: Young women with breast cancer experience inferior outcome and
      commonly manifest aggressive biological subtypes. Data is controversial regarding
      biological differences between breast tumors in young (diagnosed at <40 years of
      age) versus older women. We hypothesize there may be age-related expression
      differences in key genes for proliferation, invasion and metastasis within and
      across breast cancer subtypes, and that these differences correlate with outcome.
      METHODS: Using clinically-annotated gene expression data from 778 breast tumors
      from three public databases, we compared clinico-pathologic characteristics, mRNA
      expression of 17 selected genes, and outcome, as a function of age (< 40 years
      vs. >= 40 years). RESULTS: 14 of 17 genes were differentially expressed in tumors
      of young vs. older women, 4 of which persisted after correction for subtype and
      grade (p <=0.05). BUB1, KRT5, and MYCN were overexpressed and CXCL2
      underexpressed in young women. In multivariate analysis, overexpression of
      cytokeratin genes predicted inferior DFS only for young women. Overexpression of
      ANGPTL4 strongly predicted inferior DFS in basal but not HER2-enriched tumors in
      young women. Overexpression of cytokeratin genes and MYBL2 and low SNAI1
      expression correlated with inferior DFS in HER2-enriched tumors in younger women.
      Kaplan-Meier analysis within the basal and HER2-enriched subgroups showed that
      overexpression of cytokeratin genes was associated with inferior DFS for young,
      but not older women. CONCLUSIONS: This preliminary study reveals age- and subtype
      related differences in expression of key breast cancer genes for proliferation,
      invasion and metastasis, which correlate with prognostic differences in young
      women and suggest targeted therapies.

PMID- 25999350
TI  - Aberrant activation of Wnt/beta-catenin signaling drives proliferation of bone
      sarcoma cells.
AB  - Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory
      to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The
      Wnt signaling are evolutionarily conserved and implicated in cell proliferation
      and sarcomagenesis. However, the potential role of the Wnt signaling in bone
      sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/beta
      catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling
      loop with upregulation of specific Wnt ligands and receptors. Activation of
      Wnt/beta-catenin signaling with Wnt3a or GSK-3beta inhibitor drives the
      proliferation of bone sarcoma cells, whereas downregulation of activated Wnt
      signaling with dnTCF4 or siLEF1 suppresses bone sarcoma proliferation and induces
      cell cycle arrest. Taken together, our findings establish the evidence that
      aberrant activation of Wnt/beta-catenin pathway involving an autocrine Wnt
      singaling drives the proliferation of bone sarcoma cells, and identify the
      autocrine activation of the Wnt/beta-catenin signaling as a potential novel
      therapeutic target for bone sarcomas.

PMID- 25999349
TI  - Endoplasmic reticulum targeting in Ewing's sarcoma by the alkylphospholipid
      analog edelfosine.
AB  - Ewing's sarcoma (ES) is the second most common bone cancer in children and young
      people. Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) is the
      prototype of a family of synthetic antitumor compounds, collectively known as
      alkylphospholipid analogs (APLs). We have found that APLs ranked
      edelfosine>perifosine>erucylphosphocholine>miltefosine for their capacity to
      promote apoptosis in ES cells. Edelfosine accumulated in the endoplasmic
      reticulum (ER) and triggered an ER stress response that eventually led to caspase
      dependent apoptosis in ES cells. This apoptotic response involved mitochondrial
      mediated processes, with cytochrome c release, caspase-9 activation and
      generation of reactive oxygen species. Edelfosine-induced apoptosis was also
      dependent on sustained c-Jun NH2-terminal kinase activation. Oral administration
      of edelfosine showed a potent in vivo antitumor activity in an ES xenograft
      animal model. Histochemical staining gave evidence for ER stress response and
      apoptosis in the ES tumors isolated from edelfosine-treated mice. Edelfosine
      showed a preferential action on ES tumor cells as compared to non-transformed
      osteoblasts, and appeared to be well suited for combination therapy regimens.
      These results demonstrate in vitro and in vivo antitumor activity of edelfosine
      against ES cells that is mediated by caspase activation and ER stress, and
      provide the proof of concept for a putative edelfosine- and ER stress-mediated
      approach forES treatment. 

PMID- 25999353
TI  - An alternative to India ink stain.
AB  - Accessing India ink in rural Uganda is difficult and costly. An alternative stain
      was sought to assist in microbiological diagnoses of cryptococcal infections in
      immunosuppressed patients with meningitis. Mascara proved to be an excellent and
      cheap alternative. 

PMID- 25999354
TI  - Spontaneous rupture of pyometra manifesting as an acute abdomen: a case report.
AB  - Spontaneous perforation of pyometra is a rare entity with a reported incidence in
      the range of 0.01-0.05%. The clinical picture is similar to peritonitis arising
      from intestinal perforation and commonly the correct diagnosis is only made
      perioperatively. We report a case in an elderly postmenopausal woman presenting
      with an acute abdomen. 

PMID- 25999352
TI  - RPPA-based protein profiling reveals eIF4G overexpression and 4E-BP1 serine 65
      phosphorylation as molecular events that correspond with a pro-survival phenotype
      in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL), the most common adult leukemia, remains
      incurable despite advancements in treatment regimens over the past decade.
      Several expression profile studies have been pursued to better understand CLL
      pathogenesis. However, these large-scale studies only provide information at the
      transcriptional level. To better comprehend the differential protein changes that
      take place in CLL, we performed a reverse-phase protein array (RPPA) analysis
      using 167 different antibodies on B-cell lysates from 18 CLL patients and 6
      normal donors. From our analysis, we discovered an enrichment of protein
      alterations involved with mRNA translation, specifically upregulation of the
      translation initiator eIF4G and phosphorylation of the cap-dependent translation
      inhibitor 4E-BP1 at serine 65. Interestingly, 4E-BP1 phosphorylation occurred
      independently of AKT phosphorylation, suggesting a disconnect between PI3K/AKT
      pathway activation and 4E-BP1 phosphorylation. Based on these results, we treated
      primary CLL samples with NVP-BEZ235, a PI3K/mTOR dual inhibitor, and compared its
      apoptotic-inducing potential against the BTK inhibitor Ibrutinib and the
      PI3Kdelta inhibitor Idelalisib. We demonstrated that treatment with NVP-BEZ235
      caused greater apoptosis, greater apoptotic cleavage of eIF4G, and greater
      dephosphorylation of 4E-BP1 in primary CLL cells. Taken together, these results
      highlight the potential dependence of eIF4G overexpression and 4E-BP1
      phosphorylation in CLL survival. 

PMID- 25999351
TI  - Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts
      treatment resistance and prognosticates poor outcome in ovarian cancer.
AB  - Although ovarian cancer is a highly chemosensitive disease, it is only
      infrequently cured. One of the major reasons lies in the presence of drug
      resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped
      cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched
      samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used
      markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of
      malignant cells. ALDH1 was the most valuable marker for tracking stemness in
      vivo. The enrichment of ALDH1 expression after treatment was associated with a
      poor response to chemotherapy, with platinum resistance and independently
      prognosticated unfavorable outcome. Our results suggest that increased ALDH1
      expression after treatment identifies patients with aggressive tumor phenotypes.

PMID- 25999355
TI  - The validity of the macroscopic appearance of lymph node biopsy in the diagnosis
      of tuberculosis.
AB  - INTRODUCTION: Tuberculosis (TB) is a common disease with profound morbidity,
      mortality and effects on global public health. The differential diagnosis of
      lymphadenopathy is wide, particularly in areas where HIV is prevalent. Most
      hospitals in sub-Saharan Africa and across the developing world have limited, if
      any, histology facilities. This study will assess the validity of the assessment
      of the lymph nodes by their macroscopic appearance for the diagnosis of TB. Its
      sensitivity and specificity will be compared to full histological examination.
      METHOD: This is a single-centre prospective study conducted in a remote rural
      district hospital in Zambia over a time period of 16 months. All patients with
      palpable lymphadenopathy where TB was considered in the differential diagnosis
      were included. The patients underwent an excision lymph node biopsy. The cut
      surface was judged by the operating surgeon as to the presence of caseation. The
      excised nodes were then sent for histological examination. RESULTS: In total,
      59.8% of patients (64 of 107 patients) in this group had a final histological
      diagnosis of TB. This is equivalent to the TB disease prevalence in this group of
      patients that have palpable lymphadenopathy in this population. The diagnostic
      sensitivity based on macroscopic appearance of the lymph node was 81.25% (95% CI,
      69.5-89.9%). The specificity was 97.67% (95% CI, 87.7-99.6%). CONCLUSION: This
      study has shown that lymph node appearance is a useful diagnostic test even
      without laboratory histopathological facilities in the diagnosis of TB. This
      assessment of the macroscopic appearance is both sensitive and specific.

PMID- 25999356
TI  - Negative biomarker based male fertility evaluation: Sperm phenotypes associated
      with molecular-level anomalies.
AB  - Biomarker-based sperm analysis elevates the treatment of human infertility and
      ameliorates reproductive performance in livestock. The negative biomarker-based
      approach focuses on proteins and ligands unique to defective spermatozoa,
      regardless of their morphological phenotype, lending itself to analysis by flow
      cytometry (FC). A prime example is the spermatid specific thioredoxin
      SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of
      defective human spermatozoa. Infertile couples with high semen SPTRX3 are less
      likely to conceive by assisted reproductive therapies (ART) and more prone to
      recurrent miscarriage while low SPTRX3 has been associated with multiple ART
      births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational
      protein modifier is found on the surface of defective posttesticular spermatozoa
      and in the damaged protein aggregates, the aggresomes of spermiogenic origin.
      Semen ubiquitin content correlates negatively with fertility and conventional
      semen parameters, and with sperm binding of lectins LCA (Lens culinaris
      agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut
      agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath
      WWI Domain Binding Protein (PAWP), implicated in oocyte activation during
      fertilization, is ectopic or absent from defective human and animal spermatozoa.
      Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile
      couples and with fertility in bulls. Assays based on the above biomarkers have
      been combined into multiplex FC semen screening protocols, and the surface
      expression of lectins and ubiquitin has been utilized to develop nanoparticle
      based bull semen purification method validated by field artificial insemination
      trials. These advances go hand-in-hand with the innovation of FC-technology and
      genomics/proteomics-based biomarker discovery. 

PMID- 25999357
TI  - Spermatozoa protein alterations in infertile men with bilateral varicocele.
AB  - Among infertile men, a diagnosis of unilateral varicocele is made in 90% of
      varicocele cases and bilateral in the remaining varicocele cases. However, there
      are reports of under-diagnosis of bilateral varicocele among infertile men and
      that its prevalence is greater than 10%. In this prospective study, we aimed to
      examine the differentially expressed proteins (DEP) extracted from spermatozoa
      cells of patients with bilateral varicocele and fertile donors. Subjects
      consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men
      as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry
      system, proteomic analysis was done on pooled samples from 3 patients with
      bilateral varicocele and 5 fertile men. From these samples, 73 DEP were
      identified of which 58 proteins were differentially expressed, with 7 proteins
      unique to the bilateral varicocele group and 8 proteins to the fertile control
      group. Majority of the DEPs were observed to be associated with metabolic
      processes, stress responses, oxidoreductase activity, enzyme regulation, and
      immune system processes. Seven DEP were involved in sperm function such as
      capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were
      validated by Western blot analysis and may serve as potential biomarkers for
      bilateral varicocele. In this study, we have demonstrated for the first time the
      presence of DEP and identified proteins with distinct reproductive functions
      which are altered in infertile men with bilateral varicocele. Functional
      proteomic profiling provides insight into the mechanistic implications of
      bilateral varicocele-associated male infertility. 

PMID- 25999358
TI  - Are sperm capacitation and apoptosis the opposite ends of a continuum driven by
      oxidative stress?
AB  - This chapter explores the possibility that capacitation and apoptosis are linked
      processes joined by their common dependence on the continued generation of
      reactive oxygen species (ROS). According to this model capacitation is initiated
      in spematozoa following their release into the female reproductive tract as a
      consequence of intracellular ROS generation, which stimulates intracellular cAMP
      generation, inhibits tyrosine phosphatase activity and enhances the formation of
      oxysterols prior to their removal from the sperm surface by albumin. The
      continued generation of ROS by capacitating populations of spermatozoa eventually
      overwhelms the limited capacity of these cells to protect themselves from
      oxidative stress. As a result the over-capacitation of spermatozoa leads to a
      state of senescence and the activation of a truncated intrinsic apoptotic cascade
      characterized by enhanced mitochondrial ROS generation, lipid peroxidation,
      motility loss, caspase activation and phosphatidylserine externalization. The
      latter may be particularly important in instructing phagocytic leukocytes that
      the removal of senescent, moribund spermatozoa should be a silent process
      unaccompanied by the generation of proinflammatory cytokines. These observations
      reveal the central role played by redox chemistry in defining the life and death
      of spermatozoa. A knowledge of these mechanisms may help us to engineer novel
      solutions to both support and preserve the functionality of these highly
      specialized cells. 

PMID- 25999360
TI  - Zygotic chromosomal structural aberrations after paternal drug treatment.
AB  - In recent years, the field of male-mediated reproductive toxicology has received
      growing attention. It is now well-established that many drugs, chemicals, and
      environmental factors can harm male germ cells by inducing DNA damage. Male germ
      cells have extensive repair mechanisms that allow detection and repair of damaged
      DNA during the early phases of spermatogenesis. However, during the later phase
      of spermiogenesis, when the haploid spermatids undergo chromatin condensation and
      become transcriptionally quiescent, their ability to repair damaged DNA is lost.
      [1] ,[2] It is also thought that the highly compacted chromatin of the sperm can
      protect DNA against damage. [3] Therefore, it is expected that late spermatids
      will be most susceptible to DNA damaging agents. Unrepaired or misrepaired damage
      in the germ cells leads to the generation of spermatozoa with DNA damage that can
      be transmitted to the next generation. Fortunately, the maternal DNA repair
      machinery is capable of recognizing and repairing, at least to some degree,
      damaged paternal DNA after fertilization in the zygote. Therefore, the efficiency
      of the maternal repair machinery will greatly influence the risk of transmitting
      paternal DNA damage to offspring. [4]. 

PMID- 25999359
TI  - Role of Schwann cells in the regeneration of penile and peripheral nerves.
AB  - Schwann cells (SCs) are the principal glia of the peripheral nervous system. The
      end point of SC development is the formation of myelinating and nonmyelinating
      cells which ensheath large and small diameter axons, respectively. They play an
      important role in axon regeneration after injury, including cavernous nerve
      injury that leads to erectile dysfunction (ED). Despite improvement in radical
      prostatectomy surgical techniques, many patients still suffer from ED
      postoperatively as surgical trauma causes traction injuries and local
      inflammatory changes in the neuronal microenvironment of the autonomic fibers
      innervating the penis resulting in pathophysiological alterations in the end
      organ. The aim of this review is to summarize contemporary evidence regarding:
      (1) the origin and development of SCs in the peripheral and penile nerve system;
      (2) Wallerian degeneration and SC plastic change following peripheral and penile
      nerve injury; (3) how SCs promote peripheral and penile nerve regeneration by
      secreting neurotrophic factors; (4) and strategies targeting SCs to accelerate
      peripheral nerve regeneration. We searched PubMed for articles related to these
      topics in both animal models and human research and found numerous studies
      suggesting that SCs could be a novel target for treatment of nerve injury-induced
      ED. 

PMID- 25999361
TI  - Behavioral mechanisms of mammalian sperm guidance.
AB  - In mammals, sperm guidance in the oviduct appears essential for successful sperm
      arrival at the oocyte. Hitherto, three different potential sperm guidance
      mechanisms have been recognized: thermotaxis, rheotaxis, and chemotaxis, each of
      them using specific stimuli - a temperature gradient, fluid flow, and a
      chemoattractant gradient, respectively. Here, we review sperm behavioral in these
      mechanisms and indicate commonalities and differences between them. 

PMID- 25999362
TI  - Predictors of sperm recovery after cryopreservation in testicular cancer.
AB  - Our objective was to identify predictors of improved postthaw semen quality in
      men with testicular cancer banking sperm for fertility preservation. We reviewed
      173 individual semen samples provided by 67 men with testicular germ cell tumor
      (TGCT) who cryopreserved sperm before gonadotoxic treatment between 1994 and 2010
      at our tertiary university medical center. Our main outcomes measures were
      independent predictors for the greater postthaw total motile count (TMC) in men
      with TGCT. Men with NSGCT were more likely to be younger (P < 0.01) and had high
      cancer stage (II or III, P < 0.01) compared with men with seminoma. In our
      multiple regression model, NSGCT histology, use of density gradient purification,
      and fresh TMC > median fresh TMC each had increased odds of a postthaw TMC
      greater than median postthaw TMC. Interestingly, age, advanced cancer stage (II
      or III), rapid freezing protocol, and motility enhancer did not show increased
      odds of improved postthaw TMC in our models. In conclusion, men with TGCT or poor
      fresh TMC should consider preserving additional vials (at least 15 vials) before
      oncologic treatment. Density gradient purification should be routinely used to
      optimize postthaw TMC in men with TGCT. Larger, randomized studies evaluating
      cancer stage and various cryopreservation techniques are needed to assist in
      counseling men with TGCT regarding fertility preservation and optimizing
      cryosurvival. 

PMID- 25999363
TI  - Emotion regulation ability varies in relation to intrinsic functional brain
      architecture.
AB  - This study investigated the neural basis of individual variation in emotion
      regulation, specifically the ability to reappraise negative stimuli so as to down
      regulate negative affect. Brain functions in young adults were measured with
      functional Magnetic Resonance Imaging during three conditions: (i) attending to
      neutral pictures; (ii) attending to negative pictures and (iii) reappraising
      negative pictures. Resting-state functional connectivity was measured with
      amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently
      associated with emotion regulation. Participants reported more negative affect
      after attending to negative than neutral pictures, and less negative affect
      following reappraisal. Both attending to negative vs neutral pictures and
      reappraising vs attending to negative pictures yielded widespread activations
      that were significantly right-lateralized for attending to negative pictures and
      left-lateralized for reappraising negative pictures. Across participants, more
      successful reappraisal correlated with less trait anxiety and more positive daily
      emotion, greater activation in medial and lateral prefrontal regions, and lesser
      resting-state functional connectivity between (a) right amygdala and both medial
      prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and
      posterior visual cortices. The ability to regulate emotion, a source of
      resilience or of risk for distress, appears to vary in relation to differences in
      intrinsic functional brain architecture. 

PMID- 25999364
TI  - Microvasculature and incident atrioventricular conduction abnormalities in the
      Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - Abnormalities of the microvasculature are linked to major cardiac events, but
      their role in the development of atrioventricular conduction abnormalities (AVCA)
      is unknown. We examined the association between central retinal arteriolar
      equivalent (CRAE), a measure of the microvasculature, and incident AVCA. This
      analysis included 3975 participants free of AVCA at baseline from the Multi
      Ethnic Study of Atherosclerosis (MESA). Incident AVCA was defined as a composite
      of new heart rate-adjusted PR interval ? 200 ms (first-degree AV block) and
      advanced block (second-degree or complete AV block) detected from the MESA exam 5
      electrocardiogram (ECG). CRAE was measured from retinal photographs at exam 2.
      Both ECGs and retinal photographs were collected using standardized methods and
      read and graded at central core labs. Incident AVCA were present in 7.4% (n=290)
      of the participants, of which 94% were first-degree AV block. Incident AVCA were
      increasingly more common in participants with narrower CRAE (4.6% in Q4, 6.4% in
      Q3, 7.0% in Q2 and 10.8% in Q1, p-value for trend < 0.0001). The socio
      demographic and cardiovascular disease risk-adjusted odds of incident AVCA in the
      Q1 group (the group with the narrowest retinal arteriolar diameter) was nearly
      twice the odds in the Q4 group (OR: 1.68, 95% CI: 1.15-2.51). This association
      remained significant after adjustment for major ECG abnormalities and incident
      cardiovascular disease (Q1 vs Q4, OR: 1.65, 95% CI: 1.01-2.71). In conclusion,
      narrower retinal arteriolar caliber is associated with development of new AV
      conduction abnormalities. 

PMID- 25999365
TI  - Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3
      Cells.
AB  - OBJECTIVES: Docetaxel was the first drug with proven survival benefit in men with
      castration-resistant prostate cancer. Acquired resistance to docetaxel precedes
      fatality in castration-resistant prostate cancer. The aims of this study were to
      evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and
      to investigate the molecular mechanism of docetaxel-resistant PC-3 cells.
      METHODS: Docetaxel-resistant PC-3 cells were developed by docetaxel dose
      escalation. The global profiling of the protein expression was investigated in
      docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2
      dimensional polyacrylamide gel electrophoresis/matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. RESULTS: Forty-nine
      differential proteins were found in docetaxel-resistant PC-3 cells in comparison
      with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated,
      whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1
      were involved in the formation of tumor vessels; calreticulin, cathepsin D, and
      cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated
      protein) and microtubule-associated protein-6 were involved in drug resistance of
      tumor. CONCLUSION: It is suggested that a proteomic expression difference exists
      between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be
      helpful for further understanding the molecular mechanisms of docetaxel
      resistance in PC-3 cells.

PMID- 25999366
TI  - Rapid Aneuploidy Detection of Chromosomes 13, 18, 21, X and Y Using Quantitative
      Fluorescent Polymerase Chain Reaction with Few Microdissected Fetal Cells.
AB  - OBJECTIVES: Analysis of DNA from small numbers of cells, such as fetal cells in
      maternal blood, is a major limiting factor for their use in clinical
      applications. Traditional methods of single-cells whole genome amplification (SCs
      WGA) and accurate analysis have been challenging to date. Our purpose was to
      assess the feasibility of using a few fetal cells to determine fetal sex and
      major chromosomal abnormalities by quantitative fluorescent polymerase chain
      reaction (QF-PCR). METHODS: Cultured cells from 26 amniotic fluid samples were
      used for standard DNA extraction and recovery of 5 fetal cells by laser-capture
      microdissection. SCs-WGA was performed using the DNA from the microdissected
      cells. PCR amplification of short tandem repeats specific for chromosomes 13, 18,
      21, X and Y was performed on extracted and amplified DNA. Allele dosage and
      sexing were quantitatively analyzed following separation by capillary
      electrophoresis. RESULTS: Microsatellite QF-PCR analysis showed high concordance
      in chromosomal copy number between extracted and amplified DNA when 5 or more
      cells were used. Results were in concordance with that of conventional
      cytogenetic analysis. CONCLUSION: Satisfactory genomic coverage can be obtained
      from SCs-WGA. Clinically, SCs-WGA coupled with QF-PCR can provide a reliable,
      accurate, rapid and cost-effective method for detection of major fetal chromosome
      abnormalities.

PMID- 25999367
TI  - Erratum: The NOVA Score: A Proposal to Reduce the Need for Transesophageal
      Echocardiography in Patients With Enterococcal Bacteremia.

PMID- 25999368
TI  - Residual organic matter and microbial respiration in bottom ash: Effects on metal
      leaching and eco-toxicity.
AB  - A common assumption regarding the residual organic matter, in bottom ash, is that
      it does not represent a significant pool of organic carbon and, beyond metal-ion
      complexation process, it is of little consequence to evolution of ash/leachate
      chemistry. This article evaluates the effect of residual organic matter and
      associated microbial respiratory processes on leaching of toxic metals (i.e.
      arsenic, copper, chromium, molybdenum, nickel, lead, antimony and zinc), eco
      toxicity of ash leachates. Microbial respiration was quantified with help of a
      respirometric test equipment OXITOP control system. The effect of microbial
      respiration on metal/residual organic matter leaching and eco-toxicity was
      quantified with the help of batch leaching tests and an eco-toxicity assay -
      Daphnia magna. In general, the microbial respiration process decreased the
      leachate pH and eco-toxicity, indicating modification of bioavailability of metal
      species. Furthermore, the leaching of critical metals, such as copper and
      chromium, decreased after the respiration in both ash types (fresh and
      weathered). It was concluded that microbial respiration, if harnessed properly,
      could enhance the stability of fresh bottom ash and may promote its reuse. 

PMID- 25999369
TI  - Expression of Intermediate Filaments and Germ Cell Markers in the Developing
      Bovine Ovary: An Immunohistochemical and Laser-Assisted Microdissection Study.
AB  - In the present investigation, bovine ovary prenatal development was studied using
      immunohistochemistry and laser-assisted microdissection (LAM). A major aim of
      this study was to evaluate the protein expression pattern of intermediate
      filaments (IF) and distinguish S100 protein (S100 alpha and S100 beta protein)
      isoforms during prenatal follicle differentiation, subsequently correlating them
      with germ cell marker expression. A development-specific expression pattern of
      different keratins as well as vimentin was detected in the prenatal bovine ovary;
      K18-specific expression was found during all developmental stages (i.e. in
      surface epithelium, germ cell cord somatic cells, and follicle cells), and
      keratins 5, 7, 8, 14, and 19 and vimentin had a stage-specific expression pattern
      in the different cell populations of the prenatal ovaries. Additionally, our
      results represent new data on the expression pattern of germ cell markers during
      bovine ovary prenatal development. S100 alpha and beta protein was localized to
      oocyte cytoplasm of different follicle stages, and S100 alpha staining could be
      observed in granulosa cells. Furthermore, through isolation of characteristic
      ovary cell populations using LAM, specific confirmation of some genes of interest
      (KRT8, KRT18, S100 alpha, S100 beta, and OCT4, DDX4) could be obtained by RT-PCR
      in single cell groups of the developing bovine ovary.

PMID- 25999370
TI  - DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target
      protein degradation.
AB  - The development of effective pharmacological inhibitors of multidomain scaffold
      proteins, notably transcription factors, is a particularly challenging problem.
      In part, this is because many small-molecule antagonists disrupt the activity of
      only one domain in the target protein. We devised a chemical strategy that
      promotes ligand-dependent target protein degradation using as an example the
      transcriptional coactivator BRD4, a protein critical for cancer cell growth and
      survival. We appended a competitive antagonist of BET bromodomains to a
      phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex. The
      resultant compound, dBET1, induced highly selective cereblon-dependent BET
      protein degradation in vitro and in vivo and delayed leukemia progression in
      mice. A second series of probes resulted in selective degradation of the
      cytosolic protein FKBP12. This chemical strategy for controlling target protein
      stability may have implications for therapeutically targeting previously
      intractable proteins. 

PMID- 25999372
TI  - SOLAR CELLS. High-performance photovoltaic perovskite layers fabricated through
      intramolecular exchange.
AB  - The band gap of formamidinium lead iodide (FAPbI3) perovskites allows broader
      absorption of the solar spectrum relative to conventional methylammonium lead
      iodide (MAPbI3). Because the optoelectronic properties of perovskite films are
      closely related to film quality, deposition of dense and uniform films is crucial
      for fabricating high-performance perovskite solar cells (PSCs). We report an
      approach for depositing high-quality FAPbI3 films, involving FAPbI3
      crystallization by the direct intramolecular exchange of dimethylsulfoxide (DMSO)
      molecules intercalated in PbI2 with formamidinium iodide. This process produces
      FAPbI3 films with (111)-preferred crystallographic orientation, large-grained
      dense microstructures, and flat surfaces without residual PbI2. Using films
      prepared by this technique, we fabricated FAPbI3-based PSCs with maximum power
      conversion efficiency greater than 20%. 

PMID- 25999371
TI  - SEX DETERMINATION. A male-determining factor in the mosquito Aedes aegypti.
AB  - Sex determination in the mosquito Aedes aegypti is governed by a dominant male
      determining factor (M factor) located within a Y chromosome-like region called
      the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in
      A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two
      characteristics required of an M factor. Nix knockout with clustered regularly
      interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized
      genetic males and the production of female isoforms of two key regulators of
      sexual differentiation: doublesex and fruitless. Ectopic expression of Nix
      resulted in genetic females with nearly complete male genitalia. Thus, Nix is
      both required and sufficient to initiate male development. This study provides a
      foundation for mosquito control strategies that convert female mosquitoes into
      harmless males. 

PMID- 25999373
TI  - Moderator's view: Should all patients with ANCA-associated vasculitis be
      primarily treated with rituximab?
AB  - Experience with rituximab in patients with new ANCA-associated vasculitis (AAV)
      is still very limited, especially in patients with severe (organ- or life
      threatening) AAV. Rituximab may be more effective in anti-PR3 AAV, but
      potentially less effective in some granulomatous manifestations of AAV. We do not
      know what the response is to rituximab on the tissue level. Rituximab induction
      needs to be followed by maintenance treatment, and potentially very long
      rituximab maintenance may result in higher risk of rituximab-related
      complications (e.g. decrease in IgG levels). Long-term experience with rituximab
      in AAV is insufficient. Treatment with rituximab is more expensive than the
      standard treatment with cyclophosphamide and corticosteroids and seems to be cost
      effective only in patients primarily treated with cyclophosphamide. Rituximab can
      be used in some newly diagnosed patients with AAV (e.g. women with child-bearing
      potential, or patients with active vasculitis and severe infection), but with the
      available information, it may be too early to use it as a first-line treatment in
      all new AAV patients. 

PMID- 25999374
TI  - Con: Should all patients with anti-neutrophil cytoplasmic antibody-associated
      vasculitis be primarily treated with rituximab?
AB  - Rituximab has enriched our armamentarium in the treatment of anti-neutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis. Two randomised controlled
      trials have shown that rituximab is non-inferior compared with cyclophosphamide
      followed by azathioprine for the induction of remission. The newly diagnosed
      patients in the Rituximab in ANCA-Associated Vasculitis (RAVE) and Rituximab
      Versus Cyclophosphamide in ANCA-Associated Vasculitis (RITUXVAS) trials had a
      numerically higher response rate in the cyclophosphamide/azathioprine arm, and
      the number of such patients treated with rituximab numbered <90. We are arguing
      that in newly diagnosed patients, the evidence for rituximab requires further
      confirmation and the length of experience with a cyclophosphamide-based induction
      therapy supports it continuing as the preferred first choice for induction. Also,
      there is an absence of information regarding rituximab as 'sole' remission
      induction along with steroids in patients with advanced renal presentations or
      lung haemorrhage. Reported side effects were similar in both trials; however, the
      number of participants with at least one serious adverse event following
      rituximab induction treatment was numerically higher in the RAVE trial. In
      addition, hypogammaglobulinaemia with the need of substitution in some cases and
      late-onset neutropaenia are complications not seen with cyclophosphamide. Over
      the longer term it is unclear what relapse prevention strategy should be employed
      after rituximab, and there was a trend to a higher relapse risk after rituximab
      in the RITUXVAS trial at 2 years. Further health economic studies are required to
      understand all the costs associated with rituximab. In the context of concomitant
      underlying infectious complications, in terms of fertility concerns, especially
      in young patients, and when malignancy is underlying we would recommend the use
      of rituximab as first-line therapy. 

PMID- 25999375
TI  - Pro: Should all patients with anti-neutrophil cytoplasmic antibody-associated
      vasculitis be primarily treated with rituximab?
AB  - Randomized controlled trials have shown that rituximab is non-inferior to
      cyclophosphamide followed by azathioprine (CYC/AZA) for remission induction in
      severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
      The efficacy of rituximab is on par with CYC/AZA for 18 months, for patients with
      GPA and MPA alike, and for patients with any degree of renal impairment. The
      Rituximab in ANCA-associated Vasculitis (RAVE) trial also showed superiority of
      rituximab for patients presenting with a severe disease relapse. An exploratory
      analysis of the RAVE data further suggests that rituximab may be preferable for
      PR3-ANCA-positive patients as superiority was also achieved in that subset. When
      considering treatment options for patients with disease presentations for which
      only non-inferiority has been documented, safety concerns, compliance issues, the
      overall cost of each treatment approach to the patient, to society and to
      insurers, as well as individual patient preferences all should affect the
      decision-making process. The trials failed to uncover any difference in adverse
      events between rituximab and CYC/AZA. However, daily oral cyclophosphamide given
      for 3-6 months has measurable negative effects on fertility. Rituximab has
      certain compliance and convenience advantages. When assessing cost, the overall
      cost of a treatment, the societal context of the individual patient and not
      merely the sticker price of the drug should be considered. For all of these
      reasons, the author believes that CYC/AZA should be reserved for patients with
      newly diagnosed, MPO-ANCA-positive disease who raise no fertility, compliance or
      malignancy concerns. 

PMID- 25999376
TI  - Sarcopenia in chronic kidney disease on conservative therapy: prevalence and
      association with mortality.
AB  - BACKGROUND: In chronic kidney disease (CKD), multiple metabolic and nutritional
      abnormalities contribute to the impairment of skeletal muscle mass and function
      thus predisposing patients to the condition of sarcopenia. Herein, we
      investigated the prevalence and mortality predictive power of sarcopenia, defined
      by three different methods, in non-dialysis-dependent (NDD) CKD patients.
      METHODS: We evaluated 287 NDD-CKD patients in stages 3-5 [59.9 +/- 10.5 years;
      62% men; 49% diabetics; glomerular filtration rate (GFR) 25.0 +/- 15.8
      mL/min/1.73 m(2)]. Sarcopenia was defined as reduced muscle function assessed by
      handgrip strength (HGS <30th percentile of a population-based reference adjusted
      for sex and age) plus diminished muscle mass assessed by three different methods:
      (i) midarm muscle circumference (MAMC) <90% of reference value (A), (ii) muscle
      wasting by subjective global assessment (B) and (iii) reduced skeletal muscle
      mass index (<10.76 kg/m2 men; <6.76 kg/m2 women) estimated by bioelectrical
      impedance analysis (BIA) (C). Patients were followed for up to 40 months for all
      cause mortality, and there was no loss of follow-up. RESULTS: The prevalence of
      sarcopenia was 9.8% (A), 9.4% (B) and 5.9% (C). The kappa agreement between the
      methods were 0.69 (A versus B), 0.49 (A versus C) and 0.46 (B versus C). During
      follow-up, 51 patients (18%) died, and the frequency of sarcopenia was
      significantly higher among non-survivors. In crude Cox analysis, sarcopenia
      diagnosed by the three methods was associated with a higher hazard for mortality;
      however, only sarcopenia diagnosed by method C remained as a predictor of
      mortality after multivariate adjustment. CONCLUSIONS: The prevalence of
      sarcopenia in CKD patients on conservative therapy varies according to the method
      applied. Sarcopenia defined as reduced handgrip strength and low skeletal muscle
      mass index estimated by BIA was an independent predictor of mortality in these
      patients.

PMID- 25999377
TI  - Has Triiodothyronine Treatment of Children after Cardiopulmonary Bypass Surgery
      Any Long-Term Effects?

PMID- 25999378
TI  - Follow-up of intracranial aneurysms treated by a WEB flow disrupter: a
      comparative study of DSA and contrast-enhanced MR angiography.
AB  - OBJECTIVE: To compare contrast-enhanced MR angiography (CE-MRA) and DSA for the
      follow-up of intracranial aneurysms (IAs) treated with the Woven EndoBridge
      embolization system DL (WEB DL; Sequent Medical, Aliso Viejo, California, USA).
      MATERIALS AND METHODS: We retrospectively identified all patients treated with a
      WEB DL between November 2010 and February 2013 in 2 hospitals. The IA occlusion
      was graded on follow-up CE-MRA and DSA by 4 independent readers and by 2 readers
      reaching a consensus, respectively. Interobserver agreement for MRA and
      intertechnique agreement was evaluated by calculating linear weighted kappa.
      RESULTS: Fifteen patients with 16 IAs were included. Mean delay between MRA and
      DSA was 2 months (range 0-16 months). Interobserver agreement for MRA was
      substantial to almost perfect (kappa=0.686-0.921; mean kappa=0.809).
      Intertechnique agreement was moderate to substantial (kappa=0.579-0.724; mean
      kappa=0.669). Only three out of five inadequately occluded IAs were detected by
      MRA. CONCLUSIONS: CE-MRA is a useful tool for the follow-up of IAs treated with a
      WEB DL. However, early follow-up with DSA remains mandatory to detect
      inadequately occluded IAs.

PMID- 25999381
TI  - Erratum for Moriguchi et al., Transkingdom Genetic Transfer from Escherichia coli
      to Saccharomyces cerevisiae as a Simple Gene Introduction Tool.

PMID- 25999379
TI  - A lotus root-like appearance in carotid stenosis on optical coherence tomography.
AB  - An 82-year-old man visited the outpatient clinic of our stroke centre because of
      dizziness. He had a previous history of stroke without definite sequelae. Severe
      stenosis in the left proximal internal carotid artery (ICA) was seen on Doppler
      sonography. Conventional angiography revealed focal severe stenosis with 'string
      sign' in the left proximal ICA and delayed distal run off. Optical coherence
      tomography showed multiple channels surrounding a narrowed central lumen (lotus
      root-like appearance). Carotid stent placement with a protection device was done
      without complications. The patient was discharged in good condition 5 days after
      the procedure. 

PMID- 25999384
TI  - Intracranial Dural Arteriovenous Fistulae: Clinical Presentation and Management
      Strategies.

PMID- 25999383
TI  - Adult Cigarette Smokers at Highest Risk for Concurrent Alternative Tobacco
      Product Use Among a Racially/Ethnically and Socioeconomically Diverse Sample.
AB  - INTRODUCTION: Rates of alternative tobacco product use (ATPs; eg, cigars,
      cigarillos, pipes) among cigarette smokers are on the rise but little is known
      about the subgroups at highest risk. This study explored interactions between
      demographic, tobacco, and psychosocial factors to identify cigarette smokers at
      highest risk for ATP use from a racially/ethnically and socioeconomically diverse
      sample of adult smokers across the full smoking spectrum (nondaily, daily light,
      daily heavy). METHODS: Two-thousand three-hundred seventy-six adult cigarette
      smokers participated in an online cross-sectional survey. Quotas ensured equal
      recruitment of African American (AA), white (W), Hispanic/Latino (H) as well as
      daily and nondaily smokers. Classification and Regression Tree modeling was used
      to identify subgroups of cigarette smokers at highest risk for ATP use. RESULTS:
      51.3% were Cig+ATP smokers. Alcohol for men and age, race/ethnicity, and
      discrimination for women increased the probability of ATP use. Strikingly, 73.5%
      of men screening positive for moderate to heavy drinking and 62.2% of younger
      (<=45 years) African American/Hispanic/Latino women who experienced regular
      discrimination were Cig+ATP smokers. CONCLUSIONS: Screening for concurrent ATP
      use is necessary for the continued success of tobacco cessation efforts
      especially among male alcohol users and racial/ethnic minority women who are at
      greatest risk for ATP use.

PMID- 25999385
TI  - Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by
      Promoting M2 Macrophage Polarization.
AB  - BACKGROUND AND PURPOSE: Ly6C(hi) monocytes are generally thought to exert a
      proinflammatory role in acute tissue injury, although their impact after injuries
      to the central nervous system is poorly defined. CC chemokine receptor 2 is
      expressed on Ly6C(hi) monocytes and plays an essential role in their
      extravasation and transmigration into the brain after cerebral ischemia. We used
      a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of
      Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. METHODS:
      Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour
      followed by 23 hours of reperfusion. Mice were administered either vehicle
      (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP)
      1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we
      assessed functional outcomes, infarct volume, and quantified the immune cells in
      blood and brain by flow cytometry or immunofluorescence. Gene expression of
      selected inflammatory markers was assessed by quantitative polymerase chain
      reaction. RESULTS: Ly6C(hi) monocytes were increased 3-fold in the blood and 10
      fold in the brain after stroke, and these increases were selectively prevented by
      INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited
      markedly worse functional outcomes and larger infarct volumes, in association
      with reduced M2 polarization and increased peroxynitrite production in
      macrophages, compared with vehicle-treated mice. CONCLUSIONS: Our data suggest
      that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to
      limit brain injury and functional deficit that involves promotion of M2
      macrophage polarization.

PMID- 25999386
TI  - Leukoaraiosis Burden Significantly Modulates the Association Between Infarct
      Volume and National Institutes of Health Stroke Scale in Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS)
      provides a reliable, quantitative measure of ischemic stroke severity and is
      predicted by the infarct size. We sought to determine whether leukoaraiosis
      severity affects the association between infarct size and NIHSS. METHODS: NIHSS
      and diffusion-weighted imaging-defined infarct volumes from 312 prospectively
      enrolled patients with supratentorial, ischemic strokes were analyzed.
      Leukoaraiosis severity was graded according to the Fazekas scale and conceptually
      defined as absent (0; n=44), mild (1-2; n=106), moderate (3-4; n=105), and severe
      (5-6; n=57). ANCOVA was used to describe the effect of leukoaraiosis on the
      association between infarct volume and NIHSS. Multivariable linear regression
      models were constructed to assess whether the association of leukoaraiosis and
      infarct volume on NIHSS was independent of other clinically relevant covariates.
      RESULTS: Overall, there was a significant correlation between the infarct volume
      and NIHSS (r=0.591; P<0.001). This correlation significantly attenuated with
      increasing leukoaraiosis severity from r=0.786 (P<0.001; absent leukoaraiosis) to
      r=0.498 (P<0.001; severe leukoaraiosis) and as shown by ANCOVA (P<0.001).
      Leukoaraiosis (coefficient, 0.107; 95% confidence interval, 0.036-0.179; P=0.016)
      and infarct volume (coefficient, 0.360; 95% confidence interval, 0.305-0.416;
      P<0.001) were independently associated with a greater NIHSS deficit in the fully
      adjusted multivariable model. CONCLUSIONS: Leukoaraiosis significantly modulates
      the association between infarct volume and NIHSS. The clinical implications of
      these findings need further exploration in prospective studies but may be
      relevant to mitigate outcome differences in patients with stroke by aiding
      treatment decisions that rely on the NIHSS.

PMID- 25999387
TI  - Infratentorial Microbleeds: Another Sign of Microangiopathy in Migraine.
AB  - BACKGROUND AND PURPOSE: Migraine is a risk factor for clinical stroke and for
      subclinical white matter hyperintensities and infratentorial infarcts. These
      subclinical lesions are linked to small-vessel pathology. Cerebral microbleeds
      (CMBs) are another biomarker of small-vessel disease but have not yet been
      studied in migraine. METHODS: Identification of CMBs in 63 migraineurs (25 with
      aura/35 without aura/3 unknown aura status) and 359 controls (aged, 73-85 years)
      from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)
      magnetic resonance imaging study. We assessed the modifying role of migraine in
      the co-occurrence of CMBs, infarcts, and white matter hyperintensity-load.
      RESULTS: Infratentorial microbleeds were more prevalent in migraine without aura
      patients than controls (14% versus 4%). Prevalence of other CMBs, infarcts, and
      white matter hyperintensities did not differ between groups. Migraineurs with
      CMBs had more often infarcts than controls with CMBs (65% versus 43%). In
      comparison with controls with infarcts, migraineurs with infarcts had more
      commonly CMBs (55% versus 30%). CONCLUSIONS: Migraine, notably without aura, is
      associated with infratentorial CMBs at older age. CMBs and infarcts co-occur more
      often in migraine than in controls. This supports the hypothesis of small-vessel
      involvement in migraine pathophysiology.

PMID- 25999388
TI  - Stroke Is the Leading Cause of Death in Rural Gadchiroli, India: A Prospective
      Community-Based Study.
AB  - BACKGROUND AND PURPOSE: Stroke is an important cause of death and disability
      worldwide. However, information on stroke deaths in rural India is scarce. To
      measure the mortality burden of stroke, we conducted a community-based study in a
      rural area of Gadchiroli, one of the most backward districts of India. METHODS:
      We prospectively collected information on all deaths from April 2011 to March
      2013 and assigned causes of death using a well-validated verbal autopsy tool in a
      rural population of 94 154 individuals residing in 86 villages. Two trained
      physicians independently assigned the cause of death, and the disagreements were
      resolved by a third physician. RESULTS: Of 1599 deaths during the study period,
      229 (14.3%) deaths were caused by stroke. Stroke was the most frequent cause of
      death. For those who died because of stroke, the mean age was 67.47+/-11.8 years
      and 48.47% were women. Crude stroke mortality rate was 121.6 (95% confidence
      interval, 106.4-138.4), and age-standardized stroke mortality rate was 191.9 (95%
      confidence interval, 165.8-221.1) per 100,000 population. Of total stroke deaths,
      87.3% stroke deaths occurred at home and 46.3% occurred within the first month
      from the onset of symptoms. CONCLUSIONS: Stroke is the leading cause of death and
      accounted for 1 in 7 deaths in this rural community in Gadchiroli. There was high
      early mortality, and the mortality rate because of stroke was higher than that
      reported from previous studies from India. Stroke is emerging as a public health
      priority in rural India.

PMID- 25999389
TI  - Does Stroke Contribute to Racial Differences in Cognitive Decline?
AB  - BACKGROUND AND PURPOSE: It is unknown whether blacks' elevated risk of dementia
      is because of racial differences in acute stroke, the impact of stroke on
      cognitive health, or other factors. We investigated whether racial differences in
      cognitive decline are explained by differences in the frequency or impact of
      incident stroke between blacks and whites, controlling for baseline cognition.
      METHODS: Among 4908 black and white participants aged >=65 years free of stroke
      and cognitive impairment in the nationally representative Health and Retirement
      Study with linked Medicare data (1998-2010), we examined longitudinal changes in
      global cognition (modified version of the Telephone Interview for Cognitive
      Status) by race, before and after adjusting for time-dependent incident stroke
      followed by a race-by-incident stroke interaction term, using linear mixed
      effects models that included fixed effects of participant demographics, clinical
      factors, and cognition, and random effects for intercept and slope for time.
      RESULTS: We identified 34 of 453 (7.5%) blacks and 300 of 4455 (6.7%) whites with
      incident stroke over a mean (SD) of 4.1 (1.9) years of follow-up (P=0.53). Blacks
      had greater cognitive decline than whites (adjusted difference in modified
      version of the Telephone Interview for Cognitive Status score, 1.47 points; 95%
      confidence interval, 1.21 to 1.73 points). With further adjustment for cumulative
      incidence of stroke, the black-white difference in cognitive decline persisted.
      Incident stroke was associated with a decrease in global cognition (1.21 points;
      P<0.001) corresponding to ~7.9 years of cognitive aging. The effect of incident
      stroke on cognition did not statistically differ by race (P=0.52). CONCLUSIONS:
      In this population-based cohort of older adults, incident stroke did not explain
      black-white differences in cognitive decline or impact cognition differently by
      race.

PMID- 25999395
TI  - Impacts of Terraces on Phylogenetic Inference.
AB  - Terraces are sets of trees with precisely the same likelihood or parsimony score,
      which can be induced by missing sequences in partitioned multi-locus phylogenetic
      data matrices. The potentially large set of trees on a terrace can be
      characterized by enumeration algorithms or consensus methods that exploit the
      pattern of partial taxon coverage in the data, independent of the sequence data
      themselves. Terraces can add ambiguity and complexity to phylogenetic inference,
      particularly in settings where inference is already challenging: data sets with
      many taxa and relatively few loci. In this article we present five new findings
      about terraces and their impacts on phylogenetic inference. First, we clarify
      assumptions about partitioning scheme model parameters that are necessary for the
      existence of terraces. Second, we explore the dependence of terrace size on
      partitioning scheme and indicate how to find the partitioning scheme associated
      with the largest terrace containing a given tree. Third, we highlight the impact
      of terrace size on bootstrap estimates of confidence limits in clades, and
      characterize the surprising result that the bootstrap proportion for a clade, as
      it is usually calculated, can be entirely determined by the frequency of
      bipartitions on a terrace, with some bipartitions receiving high support even
      when incorrect. Fourth, we dissect some effects of prior distributions of edge
      lengths on the computed posterior probabilities of clades on terraces, to
      understand an example in which long edges "attract" each other in Bayesian
      inference. Fifth, we describe how assuming relationships between edge-lengths of
      different loci, as an attempt to avoid terraces, can also be problematic when
      taxon coverage is partial, specifically when heterotachy is present. Finally, we
      discuss strategies for remediation of some of these problems. One promising
      approach finds a minimal set of taxa which, when deleted from the data matrix,
      reduces the size of a terrace to a single tree. 

PMID- 25999396
TI  - New ways of seeing and being: Evaluating an acceptance and mindfulness group for
      parents of young people with intellectual disabilities who display challenging
      behaviour.
AB  - The current study presents findings from an acceptance and commitment therapy
      based intervention for family carers of children who have an
      intellectual/developmental disability and display high levels of challenging
      behaviour. The parent well-being workshops consist of two workshops incorporating
      acceptance and mindfulness-based exercises and discussions. Semi-structured
      interviews were conducted with five family carers following attendance of the
      workshops. Participants found the workshops useful and reported that they were
      better able to cope with stress. They also described how they had incorporated
      mindfulness into their daily lives and how their practice had had positive
      effects on their own well-being and on those around them (e.g. their child).
      Implications of the findings are discussed with emphasis on how the workshops can
      be included within a positive behaviour support framework. Future directions
      include a more robust quantitative evaluation, inclusion of follow-up sessions
      and the application of the workshops with other client groups and in other
      delivery formats. 

PMID- 25999397
TI  - Social pedagogy as a model to provide support for siblings of children with
      intellectual disabilities: A report of the views of the children and young people
      using a sibling support group.
AB  - The experiences of non-disabled children growing up with a sibling with an
      intellectual disability vary considerably, with reported impact ranging from
      increased mental health problems through evaluations of life enhancement.
      However, there is evidence that the net impact is neutral to positive, which was
      supported by the findings of this report of a service evaluation survey. The
      value of providing support to those young siblings is however clear. An
      established method of support is within a group of peers who also have a sibling
      with an intellectual disability, though no specific method for running this type
      of group has yet been fully explored. This article reports the views of 39
      children taking part in such a group, analysing their perspective through a
      proposed model for the operation of sibling groups: social pedagogy. It was found
      that the closer the group's activities were to social pedagogy, the more
      supported the children and young people felt. 

PMID- 25999398
TI  - Paliperidone palmitate in non-acute patients with schizophrenia previously
      unsuccessfully treated with risperidone long-acting therapy or frequently used
      conventional depot antipsychotics.
AB  - PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb
      interventional study, explored tolerability, safety and treatment response in
      adults (n = 231) with non-acute but symptomatic schizophrenia switching to
      flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with
      risperidone long-acting injectable therapy (RLAT) or conventional depot
      antipsychotics (APs). Treatment response was measured by change in Positive and
      Negative Syndrome Scale (PANSS) total score from baseline (BL) to last
      observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability
      assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and
      treatment-emergent adverse events. Significant reductions in mean PANSS total
      score were observed for all groups (-7.5 to -10.6; p ? 0.01 [BL to LOCF EP]).
      After switching to PP, more than 50% of all patients achieved ?20% and one-third
      of RLAT-treated patients even achieved ?50% improvement in PANSS total score.
      Across groups, there were significant improvements (p < 0.05) in symptom severity
      as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement
      with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and
      patient functioning with PP. PP was generally well tolerated. Clinically relevant
      benefits were observed in non-acute patients with schizophrenia switched from
      RLAT or conventional depot APs to PP. 

PMID- 25999399
TI  - Natriuretic peptide and cardiovascular risk: is it about "U"?

PMID- 25999400
TI  - Racial differences in circulating natriuretic peptide levels: the atherosclerosis
      risk in communities study.
AB  - BACKGROUND: Natriuretic peptides promote natriuresis, diuresis, and vasodilation.
      Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and
      cardiac hypertrophy, conditions more common among African Americans. Hospital
      based studies suggest that African Americans may have reduced circulating
      natriuretic peptides, as compared to Caucasians, but definitive data from
      community-based cohorts are lacking. METHODS AND RESULTS: We examined plasma N
      terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in
      9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African
      American) without prevalent cardiovascular disease at visit 4 (1996-1998).
      Multivariable linear and logistic regression analyses were performed adjusting
      for clinical covariates. Among African Americans, percent European ancestry was
      determined from genetic ancestry informative markers and then examined in
      relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP
      levels were significantly lower in African Americans (median, 43 pg/mL;
      interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36,
      124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40%
      lower (95% confidence interval [CI], -43, -36) in African Americans, compared to
      Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes,
      insulin resistance, and obesity. African-American race was also significantly
      associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22,
      7.80). In multivariable analyses in African Americans, a 10% increase in genetic
      European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted
      log NTproBNP. CONCLUSIONS: African Americans have lower levels of plasma NTproBNP
      than Caucasians, which may be partially owing to genetic variation. Low
      natriuretic peptide levels in African Americans may contribute to the greater
      risk for HTN and its sequalae in this population.

PMID- 25999401
TI  - Catheter Ablation of Atrial Fibrillation in U.S. Community Practice--Results From
      Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT
      AF).
AB  - BACKGROUND: The characteristics of patients undergoing atrial fibrillation (AF)
      ablation and subsequent outcomes in community practice are not well described.
      METHODS AND RESULTS: Using the Outcomes Registry for Better Informed Treatment of
      Atrial Fibrillation (ORBIT-AF), we investigated the prevalence and impact of
      catheter ablation of AF. Among 9935 patients enrolled, 5.3% had previous AF
      ablation. Patients with AF ablation were significantly younger, more frequently
      male, and had less anemia, chronic obstructive pulmonary disease, and previous
      myocardial infarction (P<0.05 for all analyses) than those without previous
      catheter ablation of AF. Ablated patients were more likely to have a family
      history of AF, obstructive sleep apnea, paroxysmal AF, and moderate-to-severe
      symptoms (P<0.0001 for all analyses). Patients with previous ablation were more
      often in sinus rhythm on entry into the registry (52% vs. 32%; P<0.0001). Despite
      previous ablation, 46% in the ablation group were still on antiarrhythmic
      therapy. Oral anticoagulation was prescribed in 75% of those with previous
      ablation versus 76% in those without previous ablation (P=0.5). The adjusted risk
      of death (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.52 to 1.18;
      P=0.2) and cardiovascular (CV) hospitalization (HR, 1.06; 95% CI, 0.90 to 1.26;
      P=0.5) were similar in both groups. Patients with incident AF ablation had higher
      risk of subsequent CV hospitalization than matched patients without incident
      ablation (HR, 1.67; 95% CI, 1.24 to 2.26; P=0.0008). CONCLUSIONS: In U.S.
      clinical practice, a minority of patients with AF are managed with catheter
      ablation. Subsequent to ablation, there were no significant differences in oral
      anticoagulation use or outcomes, including stroke/non-central nervous system
      embolism/transient ischemic attack or death. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01165710.

PMID- 25999402
TI  - Autonomic dysfunction determines stress-induced cardiovascular and immune
      complications in mice.
AB  - BACKGROUND: Clinical studies suggest that acute inflammation in patients with
      elevated heart rate (HR) increases morbidity and mortality. The SJL/J (SJL)
      inbred mouse strain is a unique genetic model that has higher HR and systemic and
      vascular inflammation compared with C3HeB/FeJ (C3HeB) mice. The goal of this
      study was to investigate the role of stress on cardiac and vascular complications
      between 2 strains. METHODS AND RESULTS: Radiotelemetry was used for continuous
      recordings of HR and blood pressure in mice. Hemodynamic differences between
      mouse strains were very small without stress; however, tail-cuff training
      generated mild stress and significantly increased HR (~2-fold) in SJL compared
      with C3HeB mice. Circulating proinflammatory monocytes (CD11b(+)Ly6C(H) (i))
      significantly increased in SJL mice but not in C3HeB mice after stress. Presence
      of Ly6C(+) cells in injured carotids was elevated only in SJL mice after stress;
      however, a transfer of bone marrow cells from SJL/C3HeB to C3HeB/SJL chimeras had
      no effect on HR or vascular inflammation following stress. Arterial inflammation
      (VCAM-1(+)) was greater in SJL inbred mice or SJL recipient chimeras, even
      without stress or injury. HR variability was reduced in SJL mice compared with
      C3HeB mice. CONCLUSIONS: We found that impaired parasympathetic activity is
      central for stress-induced elevation of HR and systemic and vascular
      inflammation; however, immune cells from stress-susceptible mice had no effect on
      HR or vascular inflammation in stress-protected mice.

PMID- 25999403
TI  - Activation of the intrarenal renin-angiotensin-system in murine polycystic kidney
      disease.
AB  - The mechanism for early hypertension in polycystic kidney disease (PKD) has not
      been elucidated. One potential pathway that may contribute to the elevation in
      blood pressure in PKD is the activation of the intrarenal renin-angiotensin
      system (RAS). For example, it has been shown that kidney cyst and cystic fluid
      contains renin, angiotensin II (AngII), and angiotensinogen (Agt). Numerous
      studies suggest that ciliary dysfunction plays an important role in PKD
      pathogenesis. However, it is unknown whether the primary cilium affects the
      intrarenal RAS in PKD. The purpose of this study was to determine whether loss of
      cilia or polycystin 1 (PC1) increases intrarenal RAS in mouse model of PKD. Adult
      Ift88 and Pkd1 conditional floxed allele mice with or without cre were
      administered tamoxifen to induce global knockout of the gene. Three months after
      tamoxifen injection, kidney tissues were examined by histology,
      immunofluorescence, western blot, and mRNA to assess intrarenal RAS components.
      SV40 immortalized collecting duct cell lines from hypomorphic Ift88 mouse were
      used to assess intrarenal RAS components in collecting duct cells. Mice without
      cilia and PC1 demonstrated increased kidney cyst formation, systolic blood
      pressure, prorenin, and kidney and urinary angiotensinogen levels. Interestingly
      immunofluorescence study of the kidney revealed that the prorenin receptor was
      localized to the basolateral membrane of principal cells in cilia (-) but not in
      cilia (+) kidneys. Collecting duct cAMP responses to AngII administration was
      greater in cilia (-) vs. cilia (+) cells indicating enhanced intrarenal RAS
      activity in the absence of cilia. These data suggest that in the absence of cilia
      or PC1, there is an upregulation of intrarenal RAS components and activity, which
      may contribute to elevated blood pressure in PKD. 

PMID- 25999404
TI  - Angiotensin II is required to induce exaggerated salt sensitivity in Dahl rats
      exposed to maternal separation.
AB  - We previously reported that maternal separation, rat model of early life stress,
      enhances pressor responses to acute and chronic stressors. The aims of this study
      were to determine whether Dahl salt-sensitive (DS) rats subjected to maternal
      separation (MatSep-DS) as compared to normally reared DS (Ctl-DS) rats show
      exaggerated blood pressure responses to acute behavioral stressors, such as
      restraint stress or air jet stress (AJS), or, hypertensive stimuli including
      chronic high-salt diet (4% NaCl) and angiotensin II (AngII) infusion (200
      ng/Kg/min) during 1 week. MatSep was performed in male DS rats for 3 h/day from
      postnatal days 2-14. At 8 weeks of age, rats were implanted with telemetry
      transmitters and allowed to recover. Mean arterial pressure (MAP) was not
      different between MatSep-DS and Ctl-DS rats at baseline (120 +/- 2 mmHg vs. 118
      +/- 1 mmHg, n = 4-8). Blood pressure responses during AJS and restraint stress
      were not different between MatSep-DS and Ctl-DS at 3 min. However, blood pressure
      recovery from AJS was significantly impaired in MatSep-DS rats compared to Ctl-DS
      rats (P < 0.05). 3-h stress-induced similar responses in MatSep and Ctl-DS rats.
      Chronic blood pressure responses to AngII infusion in rats fed a high-salt diet
      displayed enhanced MAP in MatSep-DS when compared with Ctl-DS rats (167 +/- 5
      mmHg vs. 152 +/- 2 mmHg, pinteraction <0.05). However, MAP increased similarly in
      both groups in response to AngII infusion or high-salt diet separately. Renal
      parameters such as proteinuria, urine flow rate, and urine electrolytes were not
      different between groups in response to each treatment. In summary, salt
      sensitivity induces exaggerated blood pressor responses only in presence of AngII
      due to early life stress. 

PMID- 25999405
TI  - The Labile Side of Iron Supplementation in CKD.
AB  - The practice of intravenous iron supplementation has grown as nephrologists have
      gradually moved away from the liberal use of erythropoiesis-stimulating agents as
      the main treatment for the anemia of CKD. This approach, together with the
      introduction of large-dose iron preparations, raises the future specter of
      inadvertent iatrogenic iron toxicity. Concerns have been raised in original
      studies and reviews about cardiac complications and severe infections that result
      from long-term intravenous iron supplementation. Regarding the iron preparations
      specifically, even though all the currently available preparations appear to be
      relatively safe in the short term, little is known regarding their long-term
      safety. In this review we summarize current knowledge of iron metabolism with an
      emphasis on the sources and potentially harmful effects of labile iron, highlight
      the approaches to identifying labile iron in pharmaceutical preparations and body
      fluids and its potential toxic role as a pathogenic factor in the complications
      of CKD, and propose methods for its early detection in at-risk patients. 

PMID- 25999406
TI  - Nuclear Factor Erythroid 2-Related Factor 2 Drives Podocyte-Specific Expression
      of Peroxisome Proliferator-Activated Receptor gamma Essential for Resistance to
      Crescentic GN.
AB  - Necrotizing and crescentic rapidly progressive GN (RPGN) is a life-threatening
      syndrome characterized by a rapid loss of renal function. Evidence suggests that
      podocyte expression of the transcription factor peroxisome proliferator-activated
      receptor gamma (PPARgamma) may prevent podocyte injury, but the function of
      glomerular PPARgamma in acute, severe inflammatory GN is unknown. Here, we
      observed marked loss of PPARgamma abundance and transcriptional activity in
      glomerular podocytes in experimental RPGN. Blunted expression of PPARgamma in
      podocyte nuclei was also found in kidneys from patients diagnosed with crescentic
      GN. Podocyte-specific Ppargamma gene targeting accentuated glomerular damage,
      with increased urinary loss of albumin and severe kidney failure. Furthermore, a
      PPARgamma gain-of-function approach achieved by systemic administration of
      thiazolidinedione (TZD) failed to prevent severe RPGN in mice with podocyte
      specific Ppargamma gene deficiency. In nuclear factor erythroid 2-related factor
      2 (NRF2)-deficient mice, loss of podocyte PPARgamma was observed at baseline.
      NRF2 deficiency markedly aggravated the course of RPGN, an effect that was
      partially prevented by TZD administration. Furthermore, delayed administration of
      TZD, initiated after the onset of RPGN, still alleviated the severity of
      experimental RPGN. These findings establish a requirement for the NRF2-PPARgamma
      cascade in podocytes, and we suggest that these transcription factors have a role
      in augmenting the tolerance of glomeruli to severe immune-complex mediated
      injury. The NRF2-PPARgamma pathway may be a therapeutic target for RPGN. 

PMID- 25999407
TI  - Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses.
AB  - Phylogenetic analyses of cellulose synthase (CesA) and cellulose synthase-like
      (Csl) families from the cellulose synthase gene superfamily were used to
      reconstruct their evolutionary origins and selection histories.
      Counterintuitively, genes encoding primary cell wall CesAs have undergone
      extensive expansion and diversification following an ancestral duplication from a
      secondary cell wall-associated CesA. Selection pressure across entire CesA and
      Csl clades appears to be low, but this conceals considerable variation within
      individual clades. Genes in the CslF clade are of particular interest because
      some mediate the synthesis of (1,3;1,4)-beta-glucan, a polysaccharide
      characteristic of the evolutionarily successful grasses that is not widely
      distributed elsewhere in the plant kingdom. The phylogeny suggests that
      duplication of either CslF6 and/or CslF7 produced the ancestor of a highly
      conserved cluster of CslF genes that remain located in syntenic regions of all
      the grass genomes examined. A CslF6-specific insert encoding approximately 55
      amino acid residues has subsequently been incorporated into the gene, or possibly
      lost from other CslFs, and the CslF7 clade has undergone a significant long-term
      shift in selection pressure. Homology modeling and molecular dynamics of the
      CslF6 protein were used to define the three-dimensional dispositions of
      individual amino acids that are subject to strong ongoing selection, together
      with the position of the conserved 55-amino acid insert that is known to
      influence the amounts and fine structures of (1,3;1,4)-beta-glucans synthesized.
      These wall polysaccharides are attracting renewed interest because of their
      central roles as sources of dietary fiber in human health and for the generation
      of renewable liquid biofuels. 

PMID- 25999409
TI  - Measuring change in amyotrophic lateral sclerosis.

PMID- 25999408
TI  - Leaf Variegation of Thylakoid Formation1 Is Suppressed by Mutations of Specific
      sigma-Factors in Arabidopsis.
AB  - Thylakoid Formation1 (THF1) has been shown to play roles in chloroplast
      development, resistance to excessive light, and chlorophyll degradation in
      Arabidopsis (Arabidopsis thaliana). To elucidate mechanisms underlying THF1
      regulated chloroplast development, we mutagenized thf1 seeds with ethyl
      methanesulfonate and screened second-site recessive mutations that suppress its
      leaf variegation phenotype. Here, we characterized a unique suppressor line, 42
      6, which displays a leaf virescent phenotype. Map-based cloning and genetic
      complementation results showed that thf1 variegation was suppressed by a mutation
      in sigma-FACTOR6 (SIG6), which is a plastid transcription factor specifically
      controlling gene expression through the plastid-encoded RNA polymerase. Northern
      blot analysis revealed that plastid gene expression was down-regulated in not
      only 42-6 and sig6 but also, thf1 at the early stage of chloroplast development.
      Interestingly, mutations in SIG2 but not in other sigma-factors also suppressed
      thf1 leaf variegation. Furthermore, we found that leaf variegation of thf1 and
      var2 could be suppressed by several virescent mutations, including yellow
      seedling1, brz-insensitive-pale green2, and nitric oxide-associated protein1,
      indicating that virescent mutations suppress leaf variegation. Taken together,
      our results provide unique insights into thf1-mediated leaf variegation, which
      might be triggered by defects in plastid gene transcription. 

PMID- 25999410
TI  - Performance and Predictive Value of a User-Independent Platform for CT Perfusion
      Analysis: Threshold-Derived Automated Systems Outperform Examiner-Driven
      Approaches in Outcome Prediction of Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Treatment strategies in acute ischemic stroke aim to
      curtail ischemic progression. Emerging paradigms propose patient subselection
      using imaging biomarkers derived from CT, CTA, and CT perfusion. We evaluated the
      performance of a fully-automated computational tool, hypothesizing enhancements
      compared with qualitative approaches. The correlation between imaging variables
      and clinical outcomes in a cohort of patients with acute ischemic stroke is
      reported. MATERIALS AND METHODS: Sixty-two patients with acute ischemic stroke
      and MCA or ICA occlusion undergoing multidetector CT, CTA, and CTP were
      retrospectively evaluated. CTP was processed on a fully operator-independent
      platform (RApid processing of PerfusIon and Diffusion [RAPID]) computing
      automated core estimates based on relative cerebral blood flow and relative
      cerebral blood volume and hypoperfused tissue volumes at varying thresholds of
      time-to-maximum. Qualitative analysis was assigned by 2 independent reviewers for
      each variable, including CT-ASPECTS, CBV-ASPECTS, CBF-ASPECTS, CTA collateral
      score, and CTA clot burden score. Performance as predictors of favorable clinical
      outcome and final infarct volume was established for each variable. RESULTS: Both
      RAPID core estimates, CT-ASPECTS, CBV-ASPECTS, and clot burden score correlated
      with favorable clinical outcome (P < .05); CBF-ASPECTS and collateral score were
      not significantly associated with favorable outcome, while hypoperfusion
      estimates were variably associated, depending on the selected time-to-maximum
      thresholds. Receiver operating characteristic analysis demonstrated disparities
      among tested variables, with RAPID core and hypoperfusion estimates outperforming
      all qualitative approaches (area under the curve, relative CBV = 0.86, relative
      CBF = 0.81; P < .001). CONCLUSIONS: Qualitative approaches to acute ischemic
      stroke imaging are subject to limitations due to their subjective nature and lack
      of physiologic information. These findings support the benefits of high-speed
      automated analysis, outperforming conventional methodologies while limiting
      delays in clinical management.

PMID- 25999411
TI  - C-Arm Flat Detector CT Parenchymal Blood Volume Thresholds for Identification of
      Infarcted Parenchyma in the Neurointerventional Suite.
AB  - BACKGROUND AND PURPOSE: C-arm flat detector CT parenchymal blood volume imaging
      allows functional assessment of the brain parenchyma in the neurointerventional
      suite. This study aimed to determine the optimal C-arm flat detector CT
      parenchymal blood volume thresholds for demarcating irreversibly infarcted brain
      parenchyma by using areas of restricted diffusion on MR imaging as a surrogate
      marker for infarction. MATERIALS AND METHODS: Twenty-six patients with delayed
      cerebral ischemia following aneurysmal SAH underwent research C-arm CT
      parenchymal blood volume scans by using a biplane angiography system and
      contemporaneous MR imaging. Infarct and peri-infarct tissue VOIs and their
      homologous VOIs in the contralateral uninvolved hemisphere were delineated on the
      basis of the review of DWI, PWI, and ADC images. Voxel-based receiver operating
      characteristic curve analysis was performed to estimate the optimal absolute and
      normalized parenchymal blood volume values for demarcating the infarct voxels.
      RESULTS: For 12 patients with areas of restricted diffusion (infarct volume, 6.38
      +/- 7.09 mL; peri-infarct tissue volume, 22.89 +/- 21.76 mL) based on the voxel
      based receiver operating characteristic curve analysis, optimal absolute and
      normalized parenchymal blood volume thresholds for infarction were 2.49 mL/100 g
      (area under curve, 0.76; sensitivity, 0.69; specificity, 0.71) and 0.67 (area
      under curve, 0.77; sensitivity, 0.69; specificity, 0.72), respectively (P value <
      .01). For the moderate-to-severely ischemic peri-infarct zone, mean parenchymal
      blood volume values of the involved hemisphere VOIs were lower compared with the
      uninvolved hemisphere VOIs (P value < .01). However, for the mild-to-moderately
      ischemic peri-infarct zone, there was no statistically significant difference
      between the mean parenchymal blood volume values of the involved and uninvolved
      hemisphere VOIs (P value > .05). CONCLUSIONS: C-arm flat detector CT parenchymal
      blood volume maps in conjunction with optimal thresholds are sensitive and
      specific for the estimation of irreversibly infarcted parenchyma. Parenchymal
      blood volume maps allow reliable detection of moderate-to-severe ischemia;
      however, the potential for underestimation of mild-to-moderate ischemia exists.

PMID- 25999412
TI  - Long-Term Follow-Up Results following Elective Treatment of Unruptured
      Intracranial Aneurysms with the Pipeline Embolization Device.
AB  - BACKGROUND AND PURPOSE: Numerous reports of treatment of wide-neck aneurysms by
      flow diverters have been published; however, long-term outcomes remain uncertain.
      This article reports the imaging results of unruptured aneurysms treated
      electively with the Pipeline Embolization Device for up to 56 months and clinical
      results for up to 61 months. MATERIALS AND METHODS: One hundred nineteen
      aneurysms in 98 patients from 3 centers admitted between August 2009 and June
      2011 were followed at 6-month, 1-year, and 2+-year postprocedural timeframes.
      Analyses on the effects of incorporated vessels, previous stent placement,
      aneurysm size, and morphology on aneurysm occlusion were performed. RESULTS: The
      1- and 2+-year imaging follow-ups were performed, on average, 13 and 28 months
      postprocedure. At 2+-year follow-up, clinical data were 100% complete and imaging
      data were complete for 103/116 aneurysms (88.8%) with a 93.2% occlusion rate.
      From 0 to 6 months, TIA, minor stroke, and major stroke rates were 4.2%, 3.4%,
      and 0.8% respectively. After 6 months, 1 patient had a TIA of uncertain cause,
      with an overall Pipeline Embolization Device-related mortality rate of 0.8%. An
      incorporated vessel was significant for a delay in occlusion (P = .009) and
      nonocclusion at 6 months and 1 year, with a delayed mean time of occlusion from
      9.1 months (95% CI, 7.1-11.1 months) to 16.7 months (95% CI, 11.4-22.0 months).
      Other factors were nonsignificant. CONCLUSIONS: The Pipeline Embolization Device
      demonstrates continued very high closure rates at 2+ years, with few delayed
      clinical adverse sequelae. The presence of an incorporated vessel in the wall of
      the aneurysm causes a delay in occlusion that approaches sidewall closure rates
      by 2 years.

PMID- 25999413
TI  - Temporal Bone CT: Improved Image Quality and Potential for Decreased Radiation
      Dose Using an Ultra-High-Resolution Scan Mode with an Iterative Reconstruction
      Algorithm.
AB  - BACKGROUND AND PURPOSE: Radiation dose in temporal bone CT imaging can be high
      due to the requirement of high spatial resolution. In this study, we assessed
      whether CT imaging of the temporal bone by using an ultra-high-resolution scan
      mode combined with iterative reconstruction provides higher spatial resolution
      and lower image noise than a z-axis ultra-high-resolution mode. MATERIALS AND
      METHODS: Patients with baseline temporal bone CT scans acquired by using a z-axis
      ultra-high-resolution protocol and a follow-up scan by using the ultra-high
      resolution-iterative reconstruction technique were identified. Images of left and
      right temporal bones were reconstructed in the axial, coronal, and Poschl planes.
      Three neuroradiologists assessed the spatial resolution of the following
      structures: round and oval windows, incudomallear and incudostapedial joints,
      basal turn spiral lamina, and scutum. The paired z-axis ultra-high-resolution and
      ultra-high-resolution-iterative reconstruction images were displayed side by side
      in random order, with readers blinded to the imaging protocol. Image noise was
      compared in ROIs over the posterior fossa. RESULTS: We identified 8 patients,
      yielding 16 sets of temporal bone images (left and right). Three sets were
      excluded because the patient underwent surgery between the 2 examinations.
      Spatial resolution was comparable (Poschl) or slightly better (axial and coronal
      planes) with ultra-high-resolution-iterative reconstruction than with z-axis
      ultra-high-resolution. A paired t test indicated that noise was significantly
      lower with ultra-high-resolution-iterative reconstruction than with z-axis ultra
      high-resolution (P < .001), with a mean noise reduction of 37% (range, 18%-49%).
      CONCLUSIONS: The ultra-high-resolution-iterative reconstruction scan mode has
      similar or slightly better resolution relative to the z-axis ultra-high
      resolution mode for CT of the temporal bone but significantly (P < .01) lower
      image noise, which may enable the dose to be reduced by approximately 50%.

PMID- 25999414
TI  - Residual Thromboembolic Material in Cerebral Arteries after Endovascular Stroke
      Therapy Can Be Identified by Dual-Energy CT.
AB  - BACKGROUND AND PURPOSE: Dual-energy CT features the opportunity to differentiate
      among up to 3 different materials because the absorption of x-rays depends on the
      applied tube voltage and the atomic number of the material. For example, it is
      possible to distinguish between blood-brain barrier disruption and an
      intracerebral hemorrhage following treatment for a stroke. The aim of this study
      was to evaluate whether dual-energy CT is capable of distinguishing intra
      arterial contrast agent from residually clotted vessels immediately after
      endovascular stroke therapy. MATERIALS AND METHODS: Sixteen patients (9 women, 7
      men; mean age, 63.6 +/- 13.09 years) were examined. Measurements were made on the
      postinterventional dual-energy CT virtual noncontrast, iodine map, and "weighted"
      brain window (weighted dual-energy) series. Postinterventional conventional
      angiography was used as the criterion standard method. RESULTS: A residual clot
      was found in 10 patients. On the virtual noncontrast series, the Hounsfield
      attenuation of the clotted arteries was higher than that in the corresponding
      perfused contralateral arteries (53.72 +/- 9.42 HU versus 41.64 +/- 7.87 HU; P <
      .05). The latter had higher absorption values on the weighted dual-energy series
      than on the virtual noncontrast series (49.37 +/- 7.44 HU versus 41.64 +/- 7.87
      HU; P < .05). The sensitivity for the detection of a residual clot was 90%; the
      specificity was 83.3%, and the accuracy was 87.5%. Interrater agreement was good
      (kappa = 0.733). CONCLUSIONS: Dual-energy CT may be valuable in the detection of
      clot persistence or early re-thrombosis without the necessity of additional
      contrast administration. However, its relevance for the prediction of outcomes
      remains to be determined in further studies.

PMID- 25999415
TI  - Establishing Amyloid PET Imaging Biomarkers: Ongoing Efforts.

PMID- 25999416
TI  - Intercellular miRNA Traffic.

PMID- 25999417
TI  - A bouquet for a broken heart: can flowers repair a damaged heart?

PMID- 25999418
TI  - Addressing Complexity in Pulmonary Hypertension: The FoxO1 Case.

PMID- 25999421
TI  - The ins and outs of mitochondrial calcium.
AB  - Calcium is thought to play an important role in regulating mitochondrial
      function. Evidence suggests that an increase in mitochondrial calcium can augment
      ATP production by altering the activity of calcium-sensitive mitochondrial matrix
      enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the
      setting of ischemia-reperfusion injury is thought to be a critical event in
      triggering cellular necrosis. For many decades, the details of how calcium
      entered the mitochondria remained a biological mystery. In the past few years,
      significant progress has been made in identifying the molecular components of the
      mitochondrial calcium uniporter complex. Here, we review how calcium enters and
      leaves the mitochondria, the growing insight into the topology, stoichiometry and
      function of the uniporter complex, and the early lessons learned from some
      initial mouse models that genetically perturb mitochondrial calcium homeostasis. 

PMID- 25999419
TI  - Mitochondrial reactive oxygen species at the heart of the matter: new therapeutic
      approaches for cardiovascular diseases.
AB  - Reactive oxygen species (ROS) have been implicated in a variety of age-related
      diseases, including multiple cardiovascular disorders. However, translation of
      ROS scavengers (antioxidants) into the clinic has not been successful. These
      antioxidants grossly reduce total levels of cellular ROS including ROS that
      participate in physiological signaling. In this review, we challenge the
      traditional antioxidant therapeutic approach that targets ROS directly with novel
      approaches that improve mitochondrial functions to more effectively treat
      cardiovascular diseases. 

PMID- 25999420
TI  - Regulated necrotic cell death: the passive aggressive side of Bax and Bak.
AB  - Although the molecular effectors of apoptotic cell death have been largely
      annotated over the past 30 years, leading to a strong biological understanding of
      this process and its importance in cell biology, cell death through necrosis has
      only recently been accepted as a similarly regulated process with definable
      molecular effectors. The mitochondria are important and central mediators of both
      apoptosis and regulated necrosis. In apoptosis, the B-cell leukemia/lymphoma 2
      (Bcl-2) family members Bcl-2-associated protein x (Bax) and Bcl-2 homologues
      antagonist/killer (Bak) undergo oligomerization in the outer mitochondrial
      membrane resulting in the release of apoptosis inducing substrates and the
      activation of caspases and nucleases. In contrast, during necrosis the
      mitochondria become dysfunctional and maladaptive in conjunction with reactive
      oxygen species production and the loss of ATP production, in part through opening
      of the mitochondrial permeability transition pore. Although regulated necrosis is
      caspase-independent, recent evidence has shown that it still requires the
      apoptotic regulators Bax/Bak, which can regulate the permeability characteristics
      of the outer mitochondrial membrane in their nonoligomerized state. Here, we
      review the nonapoptotic side of Bcl-2 family, specifically the role of Bax/Bak in
      regulated necrotic cell death. We will also discuss how these Bcl-2 family member
      effectors could be part of a larger integrated network that ultimately decides
      the fate of a given cell somewhere within a molecular continuum between apoptosis
      and regulated necrosis. 

PMID- 25999422
TI  - Maintaining ancient organelles: mitochondrial biogenesis and maturation.
AB  - The ultrastructure of the cardiac myocyte is remarkable for the high density of
      mitochondria tightly packed between sarcomeres. This structural organization is
      designed to provide energy in the form of ATP to fuel normal pump function of the
      heart. A complex system comprised of regulatory factors and energy metabolic
      machinery, encoded by both mitochondrial and nuclear genomes, is required for the
      coordinate control of cardiac mitochondrial biogenesis, maturation, and high
      capacity function. This process involves the action of a transcriptional
      regulatory network that builds and maintains the mitochondrial genome and drives
      the expression of the energy transduction machinery. This finely tuned system is
      responsive to developmental and physiological cues, as well as changes in fuel
      substrate availability. Deficiency of components critical for mitochondrial
      energy production frequently manifests as a cardiomyopathic phenotype,
      underscoring the requirement to maintain high respiration rates in the heart.
      Although a precise causative role is not clear, there is increasing evidence that
      perturbations in this regulatory system occur in the hypertrophied and failing
      heart. This review summarizes current knowledge and highlights recent advances in
      our understanding of the transcriptional regulatory factors and signaling
      networks that serve to regulate mitochondrial biogenesis and function in the
      mammalian heart. 

PMID- 25999423
TI  - How mitochondrial dynamism orchestrates mitophagy.
AB  - Mitochondria are highly dynamic, except in adult cardiomyocytes. Yet, the fission
      and fusion-promoting proteins that mediate mitochondrial dynamism are highly
      expressed in, and essential to the normal functioning of, hearts. Here, we review
      accumulating evidence supporting important roles for mitochondrial fission and
      fusion in cardiac mitochondrial quality control, focusing on the PTEN-induced
      putative kinase 1-Parkin mitophagy pathway. Based in part on recent findings from
      in vivo mouse models in which mitofusin-mediated mitochondrial fusion or dynamin
      related protein 1-mediated mitochondrial fission was conditionally interrupted in
      cardiac myocytes, we propose several new concepts that may provide insight into
      the cardiac mitochondrial dynamism-mitophagy interactome. 

PMID- 25999426
TI  - Correction.
AB  - The Circulation Research article by Keith and Bolli ("String Theory" of c-kitpos
      Cardiac Cells: A New Paradigm Regarding the Nature of These Cells That May
      Reconcile Apparently Discrepant Results. Circ Res. 2015:116:1216-1230. doi:
      10.1161/CIRCRESAHA.116.305557) states that van Berlo et al (2014) observed that
      large numbers of fibroblasts and adventitial cells, some smooth muscle and
      endothelial cells, and rare cardiomyocytes originated from c-kit positive
      progenitors. However, van Berlo et al reported that only occasional fibroblasts
      and adventitial cells derived from c-kit positive progenitors in their studies.
      Accordingly, the review has been corrected to indicate that van Berlo et al
      (2014) observed that large numbers of endothelial cells, with some smooth muscle
      cells and fibroblasts, and more rarely cardiomyocytes, originated from c-kit
      positive progenitors in their murine model. The authors apologize for this error,
      and the error has been noted and corrected in the online version of the article,
      which is available at http://circres.ahajournals.org/content/116/7/1216.full (

PMID- 25999424
TI  - From ATP to PTP and Back: A Dual Function for the Mitochondrial ATP Synthase.
AB  - Mitochondria not only play a fundamental role in heart physiology but are also
      key effectors of dysfunction and death. This dual role assumes a new meaning
      after recent advances on the nature and regulation of the permeability transition
      pore, an inner membrane channel whose opening requires matrix Ca(2+) and is
      modulated by many effectors including reactive oxygen species, matrix cyclophilin
      D, Pi (inorganic phosphate), and matrix pH. The recent demonstration that the F
      ATP synthase can reversibly undergo a Ca(2+)-dependent transition to form a
      channel that mediates the permeability transition opens new perspectives to the
      field. These findings demand a reassessment of the modifications of F-ATP
      synthase that take place in the heart under pathological conditions and of their
      potential role in determining the transition of F-ATP synthase from and energy
      conserving into an energy-dissipating device. 

PMID- 25999428
TI  - The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic
      steatohepatitis in a rodent model.
AB  - Xanthine oxidase (XO) is an enzyme involved in the production of uric acid (UA)
      from purine nucleotides. Numerous recent studies have revealed the likelihood of
      metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) or
      steatohepatitis (NASH) to be related to hyperuricemia. However, it remains
      unclear whether elevated serum UA during the development of NAFLD or NASH is a
      cause or a consequence of these diseases. In this study, the XO inhibitor
      febuxostat was administered to two types of NASH model mice. Febuxostat exerted a
      strong protective effect against NASH development induced by a high-fat diet
      containing trans fatty acid (HFDT). In contrast, methionine choline-deficient
      diet-induced NASH development not accompanied by hyperuricemia showed no UA
      normalization, suggesting that the ameliorating effect of febuxostat occurs via
      the normalization of hyperuricemia itself and/or accompanying molecular
      mechanism(s) such as oxidative stress. In the HFDT-fed mice, hyperuricemia,
      elevated alanine aminotransferase, and increased Tunnel-positive cells in the
      liver were normalized by febuxostat administration. In addition, upregulation of
      fatty acid oxidation-related genes, fibrotic change, and increases in collagen
      deposition, inflammatory cytokine expressions, and lipid peroxidation in the HFDT
      fed mice were also normalized by febuxostat administration. Taken together, these
      observations indicate that administration of febuxostat has a protective effect
      against HFDT-induced NASH development, suggesting the importance of XO in its
      pathogenesis. Thus XO inhibitors are potentially potent therapies for patients
      with NASH, particularly that associated with hyperuricemia. 

PMID- 25999427
TI  - Salmonella infection inhibits intestinal biotin transport: cellular and molecular
      mechanisms.
AB  - Infection with the nontyphoidal Salmonella is a common cause of food-borne
      disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of
      Salmonella infection could also impact host nutritional status, but little is
      known about its effect on intestinal absorption of vitamins, including biotin. We
      examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium)
      infection on intestinal biotin uptake using in vivo (streptomycin-pretreated
      mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and
      human intestinal epithelial Caco-2 cells] models. The results showed that
      infecting mice with wild-type S. typhimurium, but not with its nonpathogenic
      isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic
      biotin uptake and in level of expression of the biotin transporter, sodium
      dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco
      2 cells with S. typhimurium did not affect biotin uptake. These findings suggest
      that the effect of S. typhimurium infection is indirect and is likely mediated by
      proinflammatory cytokines, the levels of which were markedly induced in the
      intestine of S. typhimurium-infected mice. Consistent with this hypothesis,
      exposure of NCM460 cells to the proinflammatory cytokines TNF-alpha and IFN-gamma
      led to a significant inhibition of biotin uptake, sodium-dependent multivitamin
      transporter expression, and activity of the SLC5A6 promoter. The latter effects
      appear to be mediated, at least in part, via the NF-kappaB signaling pathway.
      These results demonstrate that S. typhimurium infection inhibits intestinal
      biotin uptake, and that the inhibition is mediated via the action of
      proinflammatory cytokines. 

PMID- 25999430
TI  - Imaging T Cells In Vivo.

PMID- 25999429
TI  - Long-Term Retention of 177Lu/177mLu-DOTATATE in Patients Investigated by gamma
      Spectrometry and gamma-Camera Imaging.
AB  - Dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE is
      based on patient imaging during the first week after administration and
      determination of the activity retention as a function of time for different
      tissues. For calculation of the absorbed dose, it is generally assumed that the
      long-term activity retention follows the pattern determined from the first week.
      This work aimed to investigate the validity of this assumption by performing
      additional patient measurements between 5 and 10 wk after administration. A
      further aim was to investigate to what extent absorbed dose values were affected
      when including these measurements, also taking into account the radionuclide
      impurity of (177m)Lu and build-up of secondary (177)Lu from the (177m)Lu decay.
      METHODS: A combination of methods was used: planar gamma-camera imaging as part
      of the clinical dosimetry protocol, determination of the whole-body activity
      between 5 and 9 wk after injection using spectrometric NaI(Tl) and HPGe
      detectors, and imaging between 5 and 10 wk after injection for assessment of the
      activity distribution. From these measurements the long-term retention of
      activity was determined and the relative influence on absorbed doses calculated.
      RESULTS: The most important finding was a clearly visualized tumor uptake in
      images from between 5 and 7 wk after injection and in 1 patient also kidney and
      spleen uptake in images acquired on day 33. As a consequence, the total-body time
      activity curve had a tail, which was not completely captured by imaging during
      the first week. The absorbed doses to total body and tumors obtained when
      including these late time points were on average 5%-6% higher than those obtained
      when using data acquired during the first week. The contributions to the absorbed
      dose from (177m)Lu and secondary (177)Lu were negligible. CONCLUSION: At
      approximately 5-7 wk after injection, there was a measureable amount of (177)Lu
      DOTATATE in patients, which is mainly governed by retention in tumors. For tumor
      dosimetry, imaging at a later time than the routinely used 7 d may be warranted.
      The contribution to the absorbed dose from the radionuclide impurity of (177m)Lu
      was negligible.

PMID- 25999425
TI  - Proteotoxicity and cardiac dysfunction.
AB  - Baseline physiological function of the mammalian heart is under the constant
      threat of environmental or intrinsic pathological insults. Cardiomyocyte proteins
      are thus subject to unremitting pressure to function optimally, and this depends
      on them assuming and maintaining proper conformation. This review explores the
      multiple defenses a cell may use for its proteins to assume and maintain correct
      protein folding and conformation. There are multiple quality control mechanisms
      to ensure that nascent polypeptides are properly folded and mature proteins
      maintain their functional conformation. When proteins do misfold, either in the
      face of normal or pathological stimuli or because of intrinsic mutations or post
      translational modifications, they must either be refolded correctly or recycled.
      In the absence of these corrective processes, they may become toxic to the cell.
      Herein, we explore some of the underlying mechanisms that lead to proteotoxicity.
      The continued presence and chronic accumulation of misfolded or unfolded proteins
      can be disastrous in cardiomyocytes because these misfolded proteins can lead to
      aggregation or the formation of soluble peptides that are proteotoxic. This in
      turn leads to compromised protein quality control and precipitating a downward
      spiral of the cell's ability to maintain protein homeostasis. Some underlying
      mechanisms are discussed and the therapeutic potential of interfering with
      proteotoxicity in the heart is explored. 

PMID- 25999431
TI  - 89Zr-Labeled Versus 124I-Labeled alphaHER2 Fab with Optimized Plasma Half-Life
      for High-Contrast Tumor Imaging In Vivo.
AB  - Immuno-PET imaging of the tumor antigen HER2/neu allows for the noninvasive
      detection and monitoring of oncogene expression; such detection and monitoring
      are of prognostic value in patients with breast cancer. Compared with the full
      size antibody trastuzumab, smaller protein tracers with more rapid blood
      clearance permit higher imaging contrast at earlier time points. Antigen-binding
      fragments (Fabs) of antibodies with moderately prolonged circulation achieved
      through the genetic fusion with a long, conformationally disordered chain of the
      natural amino acids Pro, Ala, and Ser (PASylation)-a biologic alternative to
      chemical conjugation with polyethylene glycol, PEG-offer a promising tracer
      format with improved pharmacokinetics for in vivo imaging. Recently, the
      transition metal radionuclide (89)Zr has attracted increasing interest for immuno
      PET studies, complementing the conventional halogen radionuclide (124)I. METHODS:
      To allow direct comparison of these 2 radioactive labels for the same protein
      tracer, the recombinant alphaHER2 Fab fused with 200 Pro, Ala, and Ser (PAS200)
      residues was either conjugated with (124)I via an iodination reagent or coupled
      with deferoxamine (Df) and complexed with (89)Zr. After confirmation of the
      stability of both radioconjugates and quality control in vitro, immuno-PET and
      biodistribution studies were performed with CD1-Foxn1(nu) mice bearing HER2
      positive human tumor xenografts. RESULTS: (89)Zr?Df-Fab-PAS200 and (124)I-Fab
      PAS200 showed specific tumor uptake of 11 and 2.3 percentage injected dose per
      gram 24 h after injection, respectively; both led to high tumor-to-blood (3.6 and
      4.4, respectively) and tumor-to-muscle (20 and 43, respectively) ratios. With
      regard to off-target accumulation, overt (124)I activity was seen in the thyroid,
      as expected, whereas high kidney uptake was evident for (89)Zr; the latter was
      probably due to glomerular filtration and reabsorption of the protein tracer in
      proximal tubular cells. CONCLUSION: Both (89)Zr- and (124)I-labeled versions of
      alphaHER2 Fab-PAS200 allowed PET tumor imaging with high contrast. With its
      residualizing radiometal, the tracer (89)Zr?Df-Fab-PAS200 showed better in vivo
      stability and higher tumor uptake.

PMID- 25999433
TI  - Finding Calcium in Noncalcified Lesions: 18F-Fluoride Offers Insights into
      Atheroma Evolution.

PMID- 25999432
TI  - Proceedings of the Second NCI-SNMMI Workshop on Targeted Radionuclide Therapy.

PMID- 25999434
TI  - Localization of Hidden Insulinomas with 68Ga-DOTA-Exendin-4 PET/CT: A Pilot
      Study.
AB  - (111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the
      detection of insulinomas. We aimed at determining whether novel PET/CT imaging
      with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is
      feasible and sensitive in detecting benign insulinomas. METHODS: (68)Ga-DOTA
      exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a
      randomized cross-over order on 5 patients with endogenous hyperinsulinemic
      hypoglycemia. The gold standard for comparison was the histologic diagnosis after
      surgery. RESULTS: In 4 patients histologic diagnosis confirmed a benign
      insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA
      exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional
      imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA
      exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas
      (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of
      4 patients. CONCLUSION: These preliminary data suggest that the use of (68)Ga
      DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

PMID- 25999435
TI  - A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients
      with Relapsed/Refractory Multiple Myeloma.
AB  - PURPOSE: Natural killer (NK) cells may play an important role in the immune
      response to multiple myeloma; however, multiple myeloma cells express killer
      immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity.
      Lenalidomide can expand and activate NK cells in parallel with its direct effects
      against multiple myeloma; however, dexamethasone may impair these favorable
      immunomodulatory properties. IPH2101, a first-in-class antiinhibitory KIR
      antibody, has acceptable safety and tolerability in multiple myeloma as a single
      agent. The present work sought to characterize lenalidomide and IPH2101 as a
      novel, steroid-sparing, dual immune therapy for multiple myeloma. EXPERIMENTAL
      DESIGN: A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was
      administered per os at 10 mg on cohort 1 and 25 mg on cohorts 2 and 3 days 1 to
      21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at
      0.2 mg/kg in cohort 1, 1 mg/kg in cohort 2, and 2 mg/kg in cohort 3. No
      corticosteroids were utilized. The primary endpoint was safety, and secondary
      endpoints included clinical activity, pharmacokinetics (PK), and pharmacodynamics
      (PD). RESULTS: The biologic endpoint of full KIR occupancy was achieved across
      the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar
      to data from a prior single-agent IPH2101 trial. Five serious adverse events
      (SAE) were reported. Five objective responses occurred. No autoimmunity was seen.
      CONCLUSIONS: These findings suggest that lenalidomide in combination with
      antiinhibitory KIR therapy warrants further investigation in multiple myeloma as
      a steroid-sparing, dual immune therapy. This trial was registered at
      www.clinicaltrials.gov (reference: NCT01217203).

PMID- 25999436
TI  - Intratumoral CD14+ Cells and Circulating CD14+HLA-DRlo/neg Monocytes Correlate
      with Decreased Survival in Patients with Clear Cell Renal Cell Carcinoma.
AB  - PURPOSE: Immunotherapeutic strategies to treat patients with renal cell carcinoma
      (RCC) offer new opportunities for disease management. Further improvements to
      immunotherapy will require additional understanding of the host response to RCC
      development. EXPERIMENTAL DESIGN: Using a novel approach to understanding the
      immune status of cancer patients, we previously showed that patients with a
      certain immune profile had decreased overall survival. Here, we examine in more
      detail the phenotypic changes in peripheral blood and the potential consequences
      of these changes in RCC patients. RESULTS: We found that CD14(+)HLA-DR(lo/neg)
      monocytes were the most predominant phenotypic change in peripheral blood of RCC
      patients, elevated nearly 5-fold above the average levels measured in healthy
      volunteers. Intratumoral and peritumoral presence of CD14 cells was an
      independent prognostic factor for decreased survival in a cohort of 375 RCC
      patients. The amount of peripheral blood CD14(+)HLA-DR(lo/neg) monocytes was
      found to correlate with the intensity of CD14 staining in tumors, suggesting that
      the measurement of these cells in blood may be a suitable surrogate for
      monitoring patient prognosis. The interaction of monocytes and tumor cells
      triggers changes in both cell types with a loss of HLA-DR expression in
      monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and
      increased production of angiogenic factors, including FGF2. CONCLUSIONS: Our
      results suggest a model of mutually beneficial interactions between tumor cells
      and monocytes that adversely affect patient outcome.

PMID- 25999438
TI  - Prospective Validation Study of the Prediction of Alcohol Withdrawal Severity
      Scale (PAWSS) in Medically Ill Inpatients: A New Scale for the Prediction of
      Complicated Alcohol Withdrawal Syndrome.
AB  - AIMS: The prevalence of alcohol use disorders (AUDs) among hospitalized medically
      ill patients exceeds 40%. Most AUD patients experience uncomplicated alcohol
      withdrawal syndrome (AWS), requiring only supportive medical intervention, while
      complicated AWS occurs in up to 20% of cases (i.e. seizures, delirium tremens).
      We aimed to prospectively test and validate the Prediction of Alcohol Withdrawal
      Severity Scale (PAWSS), a new tool to identify patients at risk for developing
      complicated AWS, in medically ill hospitalized patients. METHODS: We
      prospectively considered all subjects hospitalized to selected general medicine
      and surgery units over a 12-month period. Participants were assessed
      independently and blindly on a daily basis with PAWSS, Clinical Institute
      Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) and clinical monitoring
      throughout their admission to determine the presence and severity of AWS.
      RESULTS: Four hundred and three patients were enrolled in the study. Patients
      were grouped by PAWSS score: Group A (PAWSS < 4; considered at low risk for
      complicated AWS); Group B (PAWSS >= 4; considered at high risk for complicated
      AWS). The results of this study suggest that, using a PAWSS cutoff of 4, the
      tool's sensitivity for identifying complicated AWS is 93.1% (95%CI[77.2, 99.2%]),
      specificity is 99.5% (95%CI[98.1, 99.9%]), positive predictive value is 93.1% and
      negative predictive value is 99.5%; and has excellent inter-rater reliability
      with Lin's concordance coefficient of 0.963 (95% CI [0.936, 0.979]). CONCLUSION:
      PAWSS has excellent psychometric characteristics and predictive value among
      medically ill hospitalized patients, helping clinicians identify those at risk
      for complicated AWS and allowing for prevention and timely treatment of
      complicated AWS.

PMID- 25999437
TI  - Beer Is Less Harmful for the Liver than Plain Ethanol: Studies in Male Mice Using
      a Binge-Drinking Model.
AB  - AIMS: Mechanisms involved in the less damaging effects of beer in comparison to
      hard spirits have not yet been fully understood. The aim of the study was to
      determine if the effect of beer intake on the liver differs from that of plain
      ethanol and if so to determine mechanisms involved. METHODS: Male C57BL/6J mice
      received either ethanol, beer (ethanol content: 6 g/kg body weight) or iso
      caloric maltodextrin solution. Markers of steatosis, lipogenesis, activation of
      the toll-like receptor-4 signaling cascade and lipid export in liver and tight
      junction proteins in duodenum were measured 6 and 12 h after acute ethanol or
      beer intake. RESULTS: Alcohol ingestion resulted in a significant increase of
      hepatic triglyceride accumulation 6 and 12 h after ingestion, respectively, being
      markedly lower in mice fed beer. Expression of sterol regulatory element-binding
      protein-1c mRNA was significantly lower 12 h after alcohol or beer exposure,
      while fatty acid synthase mRNA expression was induced in livers of ethanol-fed
      mice and to a lesser extent in mice fed beer 6 h after acute alcohol ingestion.
      Protein levels of tight junction proteins in the small intestine were similar
      between groups while expression of myeloid differentiation primary response gene
      88 in livers was significantly induced in ethanol- but not in beer-fed mice.
      Concentrations of 4-hydroxynonenal protein adducts and inducible nitric oxide
      synthase protein were also only induced in livers of mice fed ethanol. Protein
      levels of apolipoprotein B were induced in livers of beer-fed mice only.
      CONCLUSION: Our data suggest that beer is less harmful on the development of
      acute alcohol-induced liver damage than plain ethanol in male mice.

PMID- 25999439
TI  - Comparison of Graft Failure Rate Between Autografts Placed via an Anatomic
      Anterior Cruciate Ligament Reconstruction Technique: A Systematic Review, Meta
      analysis, and Meta-regression.
AB  - BACKGROUND: Recent data from the Danish anterior cruciate ligament (ACL) registry
      demonstrated increased reoperation rates for hamstring tendon autografts when an
      anatomic ACL reconstruction is performed. This is consistent with reports of
      greater time needed for hamstring tendon autografts to mature compared with other
      autografts. PURPOSE: To review the literature comparing graft failure rate
      between patellar and hamstring tendon autografts placed anatomically and to
      determine if there are differences in return to preinjury activity levels between
      autografts. STUDY DESIGN: Systematic review with meta-analysis and meta
      regression. METHODS: The PubMed, MEDLINE, SPORTDiscus, and CINAHL databases were
      used to identify studies published from January 1, 2000, through March 7, 2014.
      To compare postoperative outcomes between patellar tendon and hamstring tendon
      autografts, summary event rates for graft failure and return to preinjury
      activity level were calculated. A meta-analysis was performed to calculate a
      summary odds ratio (OR) for graft failure between autografts using the studies
      that directly compared the 2 autografts. Meta-regression analyses were performed
      to assess the influence of postoperative follow-up time on graft failure rate.
      RESULTS: A total of 28 studies reported graft failures for patellar tendon (6
      studies) and hamstring tendon (26 studies) autografts used with anatomic ACL
      reconstruction; 4 of the 28 were comparison studies. Graft failure rate was not
      significantly different between patellar tendon (7.0% [95% CI, 4.6%-10.5%]) and
      hamstring tendon autografts (3.9% [95% CI, 2.7%-5.6%]). The odds of graft failure
      were slightly higher for hamstring tendon autografts (OR, 1.21 [95% CI, 0.63
      2.33]), but this difference was not significant (P = .57). The rate of patients
      returning to preinjury activity levels was not significantly different between
      patellar (n = 1 study; 58.1% [95% CI, 40.4%-73.9%]) and hamstring tendon
      autografts (n = 5 studies; 75.6% [95% CI, 43.7%-92.5%]). Overall graft failure
      rate was positively associated with postoperative follow-up time, but this effect
      was only significant with hamstring tendon autografts (P < .05). CONCLUSION:
      Differences in graft failure rate between patellar tendon and hamstring tendon
      autografts were not significant. Although follow-up time was only found to have a
      significant influence on hamstring tendon graft failure rates, this was likely
      due to the smaller sample of studies assessing patellar tendon graft failures.
      Differences in return to preinjury activity levels could not be determined due to
      the lack of studies assessing that outcome. Both patellar and hamstring tendon
      autografts demonstrate a low risk of failure and moderately high return to
      activity level after anatomic ACL reconstruction.

PMID- 25999440
TI  - A spoonful of sugar helps lymphoma cells go up.

PMID- 25999441
TI  - Pregnancy in sickle cell disease is at very high risk.

PMID- 25999442
TI  - Special delivery for ADAMTS13.

PMID- 25999443
TI  - B7-H3 ameliorates GVHD.

PMID- 25999444
TI  - JAK2V617F complete molecular remission in polycythemia vera/essential
      thrombocythemia patients treated with ruxolitinib.

PMID- 25999445
TI  - Maintenance rituximab every 2 months is more toxic than every 3 months in
      patients with non-Hodgkin lymphoma.

PMID- 25999446
TI  - No association between the presence of killer-cell immunoglobulin-like receptor
      genes and susceptibility to childhood ALL.

PMID- 25999447
TI  - Lenalidomide, idelalisib, and rituximab are unacceptably toxic in patients with
      relapsed/refractory indolent lymphoma.

PMID- 25999448
TI  - Impact of hospital volume on outcomes of patients undergoing chemotherapy for
      acute myeloid leukemia: a matched cohort study.

PMID- 25999449
TI  - Insights from response to tyrosine kinase inhibitor therapy in a rare
      myeloproliferative neoplasm with CALR mutation and BCR-ABL1.

PMID- 25999451
TI  - EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with
      evidence for a tolerogenic immune environment.
AB  - Few studies have reported Epstein-Barr virus-positive (EBV(+)) large B-cell
      lymphomas (LBCLs) in young patients without immunodeficiency. We identified 46
      such cases in patients <=45 years of age and analyzed the clinical and
      pathological characteristics. EBV(+) LBCLs affected predominantly males
      (male:female = 3.6:1), with a median age of 23 years (range, 4-45 years). All
      patients presented with lymphadenopathy and 11% also had extranodal disease.
      Morphologically, 3 patterns were identified: T-cell/histiocyte-rich large B-cell
      lymphoma-like (n = 36), gray zone lymphoma (n = 7), and diffuse LBCL-not
      otherwise specified (n = 3). Tumor cells (EBV(+) in >90% of cells) expressed B
      cell antigens, were often CD30 and PD-L1 positive, and showed a nongerminal
      center immunophenotype. A total of 93% expressed EBV latency type II and 7%
      latency type III. Indoleamine 2,3-dioxygenase was expressed on background
      accessory cells. The most common treatment regimen was rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone (58%), with local
      radiation therapy added in 21%. With a median follow-up of 22 months, 82% of
      patients are in clinical remission and only 8% died of disease. Younger patients
      achieved a significantly higher overall survival than prior series of EBV(+)
      LBCLs reported in the elderly (P < .0001). In conclusion, EBV(+) LBCLs are not
      restricted to the elderly. Young patients present with nodal disease and have a
      good prognosis. 

PMID- 25999452
TI  - Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for
      sensitive, fast, and standardized technologies.
AB  - Monitoring of minimal residual disease (MRD) has become routine clinical practice
      in frontline treatment of virtually all childhood acute lymphoblastic leukemia
      (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the
      strongest prognostic factor, allowing for risk group assignment into different
      treatment arms, ranging from significant treatment reduction to mild or strong
      intensification. Also in relapsed ALL patients and patients undergoing stem cell
      transplantation, MRD diagnostics is guiding treatment decisions. This is also why
      the efficacy of innovative drugs, such as antibodies and small molecules, are
      currently being evaluated with MRD diagnostics within clinical trials. In fact,
      MRD measurements might well be used as a surrogate end point, thereby
      significantly shortening the follow-up. The MRD techniques need to be sensitive
      (<=10(-4)), broadly applicable, accurate, reliable, fast, and affordable. Thus
      far, flow cytometry and polymerase chain reaction (PCR) analysis of rearranged
      immunoglobulin and T-cell receptor genes (allele-specific oligonucleotide [ASO]
      PCR) are claimed to meet these criteria, but classical flow cytometry does not
      reach a solid 10(-4), whereas classical ASO-PCR is time-consuming and labor
      intensive. Therefore, 2 high-throughput technologies are being explored, ie, high
      throughput sequencing and next-generation (multidimensional) flow cytometry, both
      evaluating millions of sequences or cells, respectively. Each of them has
      specific advantages and disadvantages. 

PMID- 25999453
TI  - Redefining ALL classification: toward detecting high-risk ALL and implementing
      precision medicine.
AB  - Acute lymphoblastic leukemia (ALL) is the commonest childhood tumor and remains a
      leading cause of cancer death in the young. In the last decade, microarray and
      sequencing analysis of large ALL cohorts has revolutionized our understanding of
      the genetic basis of this disease. These studies have identified new ALL
      subtypes, each characterized by constellations of structural and sequence
      alterations that perturb key cellular pathways, including lymphoid development,
      cell-cycle regulation, and tumor suppression; cytokine receptor, kinase, and Ras
      signaling; and chromatin modifications. Several of these pathways, particularly
      kinase-activating lesions and epigenetic alterations, are logical targets for new
      precision medicine therapies. Genomic profiling has also identified important
      interactions between inherited genetic variants that influence the risk of
      leukemia development and the somatic genetic alterations that are required to
      establish the leukemic clone. Moreover, sequential sequencing studies at
      diagnosis, remission, and relapse have provided important insights into the
      relationship among genetic variants, clonal heterogeneity, and the risk of
      relapse. Ongoing studies are extending our understanding of coding and noncoding
      genetic alterations in B-progenitor and T-lineage ALL and using these insights to
      inform the development of faithful experimental models to test the efficacy of
      new treatment approaches. 

PMID- 25999455
TI  - CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic
      leukemia.
AB  - Relapsed and refractory acute lymphoblastic leukemia (ALL) remains difficult to
      treat, with minimal improvement in outcomes seen in more than 2 decades despite
      advances in upfront therapy and improved survival for de novo ALL. Adoptive
      transfer of T cells engineered to express a chimeric antigen receptor (CAR) has
      emerged as a powerful targeted immunotherapy, showing striking responses in
      highly refractory populations. Complete remission (CR) rates as high as 90% have
      been reported in children and adults with relapsed and refractory ALL treated
      with CAR-modified T cells targeting the B-cell-specific antigen CD19. Distinct
      CAR designs across several studies have produced similar promising CR rates, an
      encouraging finding. Even more encouraging are durable remissions observed in
      some patients without additional therapy. Duration of remission and CAR-modified
      T-cell persistence require further study and more mature follow-up, but emerging
      data suggest these factors may distinguish CAR designs. Supraphysiologic T-cell
      proliferation, a hallmark of this therapy, contributes to both efficacy and the
      most notable toxicity, cytokine release syndrome (CRS), posing a unique challenge
      for toxicity management. This review will discuss the current landscape of CD19
      CAR clinical trials, CRS pathophysiology and management, and remaining
      challenges. 

PMID- 25999454
TI  - Inherited genetic variation in childhood acute lymphoblastic leukemia.
AB  - Although somatically acquired genomic alterations have long been recognized as
      the hallmarks of acute lymphoblastic leukemia (ALL), the last decade has shown
      that inherited genetic variations (germline) are important determinants of
      interpatient variability in ALL susceptibility, drug response, and toxicities of
      ALL therapy. In particular, unbiased genome-wide association studies have
      identified germline variants strongly associated with the predisposition to ALL
      in children, providing novel insight into the mechanisms of leukemogenesis and
      evidence for complex interactions between inherited and acquired genetic
      variations in ALL. Similar genome-wide approaches have also discovered novel
      germline genetic risk factors that independently influence ALL prognosis and
      those that strongly modify host susceptibility to adverse effects of antileukemic
      agents (eg, vincristine, asparaginase, glucocorticoids). There are examples of
      germline genomic associations that warrant routine clinical use in the treatment
      of childhood ALL (eg, TPMT and mercaptopurine dosing), but most have not reached
      this level of actionability. Future studies are needed to integrate both somatic
      and germline variants to predict risk of relapse and host toxicities, with the
      eventual goal of implementing genetics-driven precision-medicine approaches in
      ALL treatment. 

PMID- 25999456
TI  - Monoclonal antibodies in acute lymphoblastic leukemia.
AB  - With modern intensive combination polychemotherapy, the complete response (CR)
      rate in adults with acute lymphoblastic leukemia (ALL) is 80% to 90%, and the
      cure rate is 40% to 50%. Hence, there is a need to develop effective salvage
      therapies and combine novel agents with standard effective chemotherapy. ALL
      leukemic cells express several surface antigens amenable to target therapies,
      including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic
      surface antigens selectively and minimize off-target toxicity. When added to
      frontline chemotherapy, rituximab, an antibody directed against CD20, increases
      cure rates of adults with Burkitt leukemia from 40% to 80% and those with pre-B
      ALL from 35% to 50%. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to
      calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6
      to 7 months when given to patients with refractory-relapsed ALL. Blinatumomab, a
      biallelic T cell engaging the CD3-CD19 monoclonal antibody, also resulted in
      overall response rates of 40% to 50% and a median survival of 6.5 months in a
      similar refractory-relapsed population. Other promising monoclonal antibodies
      targeting CD20 (ofatumumab and obinutuzumab) or CD19 or CD20 and bound to
      different cytotoxins or immunotoxins are under development. Combined modalities
      of chemotherapy and the novel monoclonal antibodies are under investigation. 

PMID- 25999458
TI  - Introduction to the review series on acute lymphoblastic leukemia.

PMID- 25999459
TI  - Towards a public health profession: the roles of essential public health
      operations and lists of competences.

PMID- 25999460
TI  - Will European Reference Networks herald a new era of care for patients with rare
      and complex diseases?

PMID- 25999457
TI  - VAMP-7 links granule exocytosis to actin reorganization during platelet
      activation.
AB  - Platelet activation results in profound morphologic changes accompanied by
      release of granule contents. Recent evidence indicates that fusion of granules
      with the plasma membrane during activation provides auxiliary membrane to cover
      growing actin structures. Yet little is known about how membrane fusion is
      coupled with actin reorganization. Vesicle-associated membrane protein (VAMP)-7
      is found on platelet vesicles and possesses an N-terminal longin domain capable
      of linking exocytosis to cytoskeletal remodeling. We have evaluated platelets
      from VAMP-7(-/-) mice to determine whether this VAMP isoform contributes to
      granule release and platelet spreading. VAMP-7(-/-) platelets demonstrated a
      partial defect in dense granule exocytosis and impaired aggregation. alpha
      Granule exocytosis from VAMP-7(-/-) platelets was diminished both in vitro and in
      vivo during thrombus formation. Consistent with a role of VAMP-7 in cytoskeletal
      remodeling, spreading on matrices was decreased in VAMP-7(-/-) platelets compared
      to wild-type controls. Immunoprecipitation of VAMP-7 revealed an association with
      VPS9-domain ankyrin repeat protein (VARP), an adaptor protein that interacts with
      both membrane-bound and cytoskeleton proteins and with Arp2/3. VAMP-7, VARP, and
      Arp2/3 localized to the platelet periphery during spreading. These studies
      demonstrate that VAMP-7 participates in both platelet granule secretion and
      spreading and suggest a mechanism whereby VAMP-7 links granule exocytosis with
      actin reorganization. 

PMID- 25999461
TI  - The attack on universal health coverage in Europe: recession, austerity and unmet
      needs.

PMID- 25999462
TI  - Bailouts, austerity and the erosion of health coverage in Southern Europe and
      Ireland.

PMID- 25999463
TI  - The attack on universal health coverage in Europe: different effects in different
      parts of Europe.

PMID- 25999464
TI  - European public health news.

PMID- 25999465
TI  - Cold weather kills far more people than hot weather, study shows.

PMID- 25999466
TI  - Tests to predict imminent delivery in threatened preterm labour.

PMID- 25999469
TI  - Politicians must stop using NHS as "commodity" to win votes, say GPs.

PMID- 25999471
TI  - Finances, targets, and workforce are on NHS agenda for next parliament, hears
      meeting.

PMID- 25999468
TI  - Experimental design of complement component 5a-induced acute lung injury (C5a
      ALI): a role of CC-chemokine receptor type 5 during immune activation by
      anaphylatoxin.
AB  - Excessive activation of the complement system is detrimental in acute
      inflammatory disorders. In this study, we analyzed the role of complement-derived
      anaphylatoxins in the pathogenesis of experimental acute lung injury/acute
      respiratory distress syndrome (ALI/ARDS) in C57BL/6J mice. Intratracheal
      administration of recombinant mouse complement component (C5a) caused alveolar
      inflammation with abundant recruitment of Ly6-G(+)CD11b(+) leukocytes to the
      alveolar spaces and severe alveolar-capillary barrier dysfunction (C5a-ALI;
      EC(50[C5a]) = 20 ng/g body weight). Equimolar concentrations of C3a or
      desarginated C5a (C5a(desArg)) did not induce alveolar inflammation. The severity
      of C5a-ALI was aggravated in C5-deficient mice. Depletion of Ly6-G(+) cells and
      use of C5aR1(-/-) bone marrow chimeras suggested an essential role of C5aR1(+)
      hematopoietic cells in C5a-ALI. Blockade of PI3K/Akt and MEK1/2 kinase pathways
      completely abrogated lung injury. The mechanistic description is that C5a altered
      the alveolar cytokine milieu and caused significant release of CC-chemokines.
      Mice with genetic deficiency of CC-chemokine receptor (CCR) type 5, the common
      receptor of chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5, displayed
      reduced lung damage. Moreover, treatment with a CCR5 antagonist, maraviroc, was
      protective against C5a-ALI. In summary, our results suggest that the detrimental
      effects of C5a in this model are partly mediated through CCR5 activation
      downstream of C5aR1, which may be evaluated for potential therapeutic
      exploitation in ALI/ARDS.

PMID- 25999470
TI  - Interindividual differences in response to treatment with butyrate-producing
      Butyricicoccus pullicaecorum 25-3T studied in an in vitro gut model.
AB  - Butyrate-producing bacteria are promising probiotic candidates to target
      microbial dysbiosis in gastrointestinal disorders like inflammatory bowel
      diseases. Butyricicoccus pullicaecorum 25-3(T), a butyrate-producing clostridial
      cluster IV strain, is such a candidate. Little is known about its abundance in
      the colon microbiota and its butyrogenic properties. We used the M-SHIME((r)), an
      in vitro simulator for the human intestinal microbial ecosystem, to study the
      effect of supplementing a single dose of B. pullicaecorum 25-3(T) on lumen- and
      mucus-associated microbiota of eight individuals. Butyricicoccus pullicaecorum
      was more abundant in mucus-associated microbiota compared with lumen microbiota.
      Supplementation with a single dose of B. pullicaecorum 25-3(T) resulted in a
      temporary increase in B. pullicaecorum bacteria in lumen compartment of all
      individuals. In two cases, the responders, an increased butyrate production was
      observed as compared with the control. 16S rRNA gene amplicon sequencing revealed
      the microbiota of responders to be different as compared to non-responder
      microbiota. We can conclude that B. pullicaecorum 25-3(T) is a mucus-associated
      bacterium whose potency to stimulate butyrate production is characterized by a
      large interindividual variability in terms of composition of the receiving
      microbial community.

PMID- 25999472
TI  - Indian minister denies plan for nurse practitioners to fill doctor gap.

PMID- 25999467
TI  - Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding.
AB  - RAS proteins are signal transduction gatekeepers that mediate cell growth,
      survival, and differentiation through interactions with multiple effector
      proteins. The RAS effector RAS- and RAB-interacting protein 1 (RIN1) activates
      its own downstream effectors, the small GTPase RAB5 and the tyrosine kinase
      Abelson tyrosine-protein kinase (ABL), to modulate endocytosis and cytoskeleton
      remodeling. To identify ABL substrates downstream of RAS-to-RIN1 signaling, we
      examined human HEK293T cells overexpressing components of this pathway. Proteomic
      analysis revealed several novel phosphotyrosine peptides, including Harvey rat
      sarcoma oncogene (HRAS)-pTyr(137). Here we report that ABL phosphorylates
      tyrosine 137 of H-, K-, and NRAS. Increased RIN1 levels enhanced HRAS-Tyr(137)
      phosphorylation by nearly 5-fold, suggesting that RAS-stimulated RIN1 can drive
      ABL-mediated RAS modification in a feedback circuit. Tyr(137) is well conserved
      among RAS orthologs and is part of a transprotein H-bond network. Crystal
      structures of HRAS(Y137F) and HRAS(Y137E) revealed conformation changes radiating
      from the mutated residue. Although consistent with Tyr(137) participation in
      allosteric control of HRAS function, the mutations did not alter intrinsic GTP
      hydrolysis rates in vitro. HRAS-Tyr(137) phosphorylation enhanced HRAS signaling
      capacity in cells, however, as reflected by a 4-fold increase in the association
      of phosphorylated HRAS(G12V) with its effector protein RAF proto-oncogene
      serine/threonine protein kinase 1 (RAF1). These data suggest that RAS
      phosphorylation at Tyr(137) allosterically alters protein conformation and
      effector binding, providing a mechanism for effector-initiated modulation of RAS
      signaling.

PMID- 25999475
TI  - A high-content screening microscopy approach to dissect the role of Rab proteins
      in Golgi-to-ER retrograde trafficking.
AB  - Here, we describe a high-content microscopy-based screen that allowed us to
      systematically assess and rank proteins involved in Golgi-to-endoplasmic
      reticulum (ER) retrograde transport in mammalian cells. Using a cell line stably
      expressing a GFP-tagged Golgi enzyme, we used brefeldin A treatment to stimulate
      the production of Golgi-to-ER carriers and then quantitatively analysed
      populations of cells for changes in this trafficking event. Systematic RNA
      interference (RNAi)-based depletion of 58 Rab GTPase proteins and 12 Rab
      accessory proteins of the PRAF, YIPF and YIF protein families revealed that nine
      of these were strong regulators. In addition to demonstrating roles for Rab1a,
      Rab1b, Rab2a, and Rab6a or Rab6a' in this transport step, we also identified
      Rab10 and Rab11a as playing a role and being physically present on a proportion
      of the Golgi-to-ER tubular intermediates. Combinatorial depletions of Rab
      proteins also revealed previously undescribed functional co-operation and
      physical co-occurrence between several Rab proteins. Our approach therefore
      provides a novel and robust strategy for a more complete investigation of the
      molecular components required to regulate Golgi-to-ER transport in mammalian
      cells. 

PMID- 25999473
TI  - CALHM1 ion channel elicits amyloid-beta clearance by insulin-degrading enzyme in
      cell lines and in vivo in the mouse brain.
AB  - Alzheimer's disease is characterized by amyloid-beta (Abeta) peptide accumulation
      in the brain. CALHM1, a cell-surface Ca(2+) channel expressed in brain neurons,
      has anti-amyloidogenic properties in cell cultures. Here, we show that CALHM1
      controls Abeta levels in vivo in the mouse brain through a previously
      unrecognized mechanism of regulation of Abeta clearance. Using pharmacological
      and genetic approaches in cell lines, we found that CALHM1 ion permeability and
      extracellular Ca(2+) were required for the Abeta-lowering effect of CALHM1. Abeta
      level reduction by CALHM1 could be explained by an increase in extracellular
      Abeta degradation by insulin-degrading enzyme (IDE), extracellular secretion of
      which was strongly potentiated by CALHM1 activation. Importantly, Calhm1 knockout
      in mice reduced IDE enzymatic activity in the brain, and increased endogenous
      Abeta concentrations by up to ~50% in both the whole brain and primary neurons.
      Thus, CALHM1 controls Abeta levels in cell lines and in vivo by facilitating
      neuronal and Ca(2+)-dependent degradation of extracellular Abeta by IDE. This
      work identifies CALHM1 ion channel as a potential target for promoting amyloid
      clearance in Alzheimer's disease. 

PMID- 25999474
TI  - TM9 family proteins control surface targeting of glycine-rich transmembrane
      domains.
AB  - TM9 family proteins (also named Phg1 proteins) have been previously shown to
      control cell adhesion by determining the cell surface localization of adhesion
      proteins such as the Dictyostelium SibA protein. Here, we show that the glycine
      rich transmembrane domain (TMD) of SibA is sufficient to confer Phg1A-dependent
      surface targeting to a reporter protein. Accordingly, in Dictyostelium phg1A
      knockout (KO) cells, proteins with glycine-rich TMDs were less efficiently
      transported out of the endoplasmic reticulum (ER) and to the cell surface. Phg1A,
      as well as its human ortholog TM9SF4 specifically associated with glycine-rich
      TMDs. In human cells, genetic inactivation of TM9SF4 resulted in an increased
      retention of glycine-rich TMDs in the endoplasmic reticulum, whereas TM9SF4
      overexpression enhanced their surface localization. The bulk of the TM9SF4
      protein was localized in the Golgi complex and a proximity-ligation assay
      suggested that it might interact with glycine-rich TMDs. Taken together, these
      results suggest that one of the main roles of TM9 proteins is to serve as
      intramembrane cargo receptors controlling exocytosis and surface localization of
      a subset of membrane proteins. 

PMID- 25999476
TI  - The I-BAR protein Ivy1 is an effector of the Rab7 GTPase Ypt7 involved in vacuole
      membrane homeostasis.
AB  - Membrane fusion at the vacuole depends on a conserved machinery that includes
      SNAREs, the Rab7 homolog Ypt7 and its effector HOPS. Here, we demonstrate that
      Ypt7 has an unexpected additional function by controlling membrane homeostasis
      and nutrient-dependent signaling on the vacuole surface. We show that Ivy1, the
      yeast homolog of mammalian missing-in-metastasis (MIM), is a vacuolar effector of
      Ypt7-GTP and interacts with the EGO/ragulator complex, an activator of the target
      of rapamycin kinase complex 1 (TORC1) on vacuoles. Loss of Ivy1 does not affect
      EGO vacuolar localization and function. In combination with the deletion of
      individual subunits of the V-ATPase, however, we observed reduced TORC1 activity
      and massive enlargement of the vacuole surface. Consistent with this, Ivy1
      localizes to invaginations at the vacuole surface and on liposomes in a
      phosphoinositide- and Ypt7-GTP-controlled manner, which suggests a role in
      microautophagy. Our data, thus, reveal that Ivy1 is a novel regulator of vacuole
      membrane homeostasis with connections to TORC1 signaling. 

PMID- 25999478
TI  - Pregnant women are advised to seek medical advice if they need paracetamol for
      more than one day.

PMID- 25999477
TI  - Akt-mediated phosphorylation increases the binding affinity of hTERT for importin
      alpha to promote nuclear translocation.
AB  - Telomeres are essential for chromosome integrity and protection, and their
      maintenance requires the ribonucleoprotein enzyme telomerase. Previously, we have
      shown that human telomerase reverse transcriptase (hTERT) contains a bipartite
      nuclear localization signal (NLS; residues 222-240) that is responsible for
      nuclear import, and that Akt-mediated phosphorylation of residue S227 is
      important for efficient nuclear import of hTERT. Here, we show that hTERT binds
      to importin-alpha proteins through the bipartite NLS and that this heterodimer
      then forms a complex with importin-beta proteins to interact with the nuclear
      pore complex. Depletion of individual importin-alpha proteins results in a
      failure of hTERT nuclear import, and the resulting cytoplasmic hTERT is degraded
      by ubiquitin-dependent proteolysis. Crystallographic analysis reveals that the
      bipartite NLS interacts with both the major and minor sites of importin-alpha
      proteins. We also show that Akt-mediated phosphorylation of S227 increases the
      binding affinity for importin-alpha proteins and promotes nuclear import of
      hTERT, thereby resulting in increased telomerase activity. These data provide
      details of a binding mechanism that enables hTERT to interact with the nuclear
      import receptors and of the control of the dynamic nuclear transport of hTERT
      through phosphorylation. 

PMID- 25999479
TI  - We cannot keep ignoring the crisis in social care.

PMID- 25999480
TI  - Oceans and Earth's habitability.

PMID- 25999482
TI  - Microbiology. Leaf bacteria fertilize trees, researchers claim.

PMID- 25999483
TI  - Earth science. Alarm over a sinking delta.

PMID- 25999484
TI  - Biomedical research. Canadian registry to track thousands of pot smokers.

PMID- 25999485
TI  - Human evolution. Ancient DNA pinpoints Paleolithic liaison in Europe.

PMID- 25999486
TI  - Europe. E.U. commission promises to listen to scientists.

PMID- 25999487
TI  - Regenerative medicine. 'Rejuvenating' protein doubted.

PMID- 25999488
TI  - The drug push.

PMID- 25999489
TI  - The new shape of fusion.

PMID- 25999490
TI  - Science and society. Debating a testosterone "sex gap".

PMID- 25999491
TI  - Neuroscience. Reading the mind to move the body.

PMID- 25999492
TI  - Microbiology. Just add lanthanides.

PMID- 25999493
TI  - Organic chemistry. Streamlining amine synthesis.

PMID- 25999494
TI  - Marine biology. Uncovering hidden worlds of ocean biodiversity.

PMID- 25999495
TI  - Cancer. Preprocancer.

PMID- 25999496
TI  - Eugenics lurk in the shadow of CRISPR.

PMID- 25999497
TI  - Carnivore coexistence: wilderness not required.

PMID- 25999498
TI  - Outside the tower. Honing the climate change message.

PMID- 25999499
TI  - Asian archaeology. Comment on "Agriculture facilitated permanent human occupation
      of the Tibetan Plateau after 3600 B.P. ".
AB  - Chen et al. (Reports, 16 January 2015, p. 248) argued that early Tibetan
      agriculturalists pushed the limits of farming up to 4000 meters above sea level.
      We contend that this argument is incompatible with the growing requirements of
      barley. It is necessary to clearly define past crop niches to create better
      models for the complex history of the occupation of the plateau. 

PMID- 25999500
TI  - Asian archaeology. Response to Comment on "Agriculture facilitated permanent
      human occupation of the Tibetan Plateau after 3600 B.P.".
AB  - Guedes et al. have drawn attention to a mismatch between the predictions of their
      "thermal niche model" and the records we have published of early barley finds in
      the northeastern Tibetan Plateau. Here, we consider how that mismatch usefully
      draws our attention to the additional variables that may account for it-namely,
      variations in genetic expression and agricultural practice. 

PMID- 25999501
TI  - Tara Oceans. Tara Oceans studies plankton at planetary scale. Introduction.

PMID- 25999503
TI  - Organic chemistry. Practical olefin hydroamination with nitroarenes.
AB  - The synthesis and functionalization of amines are fundamentally important in a
      vast range of chemical contexts. We present an amine synthesis that repurposes
      two simple feedstock building blocks: olefins and nitro(hetero)arenes. Using
      readily available reactants in an operationally simple procedure, the protocol
      smoothly yields secondary amines in a formal olefin hydroamination. Because of
      the presumed radical nature of the process, hindered amines can easily be
      accessed in a highly chemoselective transformation. A screen of more than 100
      substrate combinations showcases tolerance of numerous unprotected functional
      groups such as alcohols, amines, and even boronic acids. This process is
      orthogonal to other aryl amine syntheses, such as the Buchwald-Hartwig, Ullmann,
      and classical amine-carbonyl reductive aminations, as it tolerates aryl halides
      and carbonyl compounds. 

PMID- 25999502
TI  - Tumor evolution. High burden and pervasive positive selection of somatic
      mutations in normal human skin.
AB  - How somatic mutations accumulate in normal cells is central to understanding
      cancer development but is poorly understood. We performed ultradeep sequencing of
      74 cancer genes in small (0.8 to 4.7 square millimeters) biopsies of normal skin.
      Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the
      burden of somatic mutations averaged two to six mutations per megabase per cell,
      similar to that seen in many cancers, and exhibited characteristic signatures of
      exposure to ultraviolet light. Remarkably, multiple cancer genes are under strong
      positive selection even in physiologically normal skin, including most of the key
      drivers of cutaneous squamous cell carcinomas. Positively selected mutations were
      found in 18 to 32% of normal skin cells at a density of ~140 driver mutations per
      square centimeter. We observed variability in the driver landscape among
      individuals and variability in the sizes of clonal expansions across genes. Thus,
      aged sun-exposed skin is a patchwork of thousands of evolving clones with over a
      quarter of cells carrying cancer-causing mutations while maintaining the
      physiological functions of epidermis. 

PMID- 25999504
TI  - Carbon cycle. The dominant role of semi-arid ecosystems in the trend and
      variability of the land CO2 sink.
AB  - The growth rate of atmospheric carbon dioxide (CO2) concentrations since
      industrialization is characterized by large interannual variability, mostly
      resulting from variability in CO2 uptake by terrestrial ecosystems (typically
      termed carbon sink). However, the contributions of regional ecosystems to that
      variability are not well known. Using an ensemble of ecosystem and land-surface
      models and an empirical observation-based product of global gross primary
      production, we show that the mean sink, trend, and interannual variability in CO2
      uptake by terrestrial ecosystems are dominated by distinct biogeographic regions.
      Whereas the mean sink is dominated by highly productive lands (mainly tropical
      forests), the trend and interannual variability of the sink are dominated by semi
      arid ecosystems whose carbon balance is strongly associated with circulation
      driven variations in both precipitation and temperature. 

PMID- 25999505
TI  - Glacier mass loss. Dynamic thinning of glaciers on the Southern Antarctic
      Peninsula.
AB  - Growing evidence has demonstrated the importance of ice shelf buttressing on the
      inland grounded ice, especially if it is resting on bedrock below sea level. Much
      of the Southern Antarctic Peninsula satisfies this condition and also possesses a
      bed slope that deepens inland. Such ice sheet geometry is potentially unstable.
      We use satellite altimetry and gravity observations to show that a major portion
      of the region has, since 2009, destabilized. Ice mass loss of the marine
      terminating glaciers has rapidly accelerated from close to balance in the 2000s
      to a sustained rate of -56 +/- 8 gigatons per year, constituting a major fraction
      of Antarctica's contribution to rising sea level. The widespread, simultaneous
      nature of the acceleration, in the absence of a persistent atmospheric forcing,
      points to an oceanic driving mechanism. 

PMID- 25999506
TI  - Neurophysiology. Decoding motor imagery from the posterior parietal cortex of a
      tetraplegic human.
AB  - Nonhuman primate and human studies have suggested that populations of neurons in
      the posterior parietal cortex (PPC) may represent high-level aspects of action
      planning that can be used to control external devices as part of a brain-machine
      interface. However, there is no direct neuron-recording evidence that human PPC
      is involved in action planning, and the suitability of these signals for
      neuroprosthetic control has not been tested. We recorded neural population
      activity with arrays of microelectrodes implanted in the PPC of a tetraplegic
      subject. Motor imagery could be decoded from these neural populations, including
      imagined goals, trajectories, and types of movement. These findings indicate that
      the PPC of humans represents high-level, cognitive aspects of action and that the
      PPC can be a rich source for cognitive control signals for neural prosthetics
      that assist paralyzed patients. 

PMID- 25999507
TI  - Virology. A virus that infects a hyperthermophile encapsidates A-form DNA.
AB  - Extremophiles, microorganisms thriving in extreme environmental conditions, must
      have proteins and nucleic acids that are stable at extremes of temperature and
      pH. The nonenveloped, rod-shaped virus SIRV2 (Sulfolobus islandicus rod-shaped
      virus 2) infects the hyperthermophilic acidophile Sulfolobus islandicus, which
      lives at 80 degrees C and pH 3. We have used cryo-electron microscopy to generate
      a three-dimensional reconstruction of the SIRV2 virion at ~4 angstrom resolution,
      which revealed a previously unknown form of virion organization. Although almost
      half of the capsid protein is unstructured in solution, this unstructured region
      folds in the virion into a single extended alpha helix that wraps around the DNA.
      The DNA is entirely in the A-form, which suggests a common mechanism with
      bacterial spores for protecting DNA in the most adverse environments. 

PMID- 25999508
TI  - RNA structure. Structure of the HIV-1 RNA packaging signal.
AB  - The 5' leader of the HIV-1 genome contains conserved elements that direct
      selective packaging of the unspliced, dimeric viral RNA into assembling
      particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we
      determined the structure of a 155-nucleotide region of the leader that is
      independently capable of directing packaging (core encapsidation signal;
      Psi(CES)). The RNA adopts an unexpected tandem three-way junction structure, in
      which residues of the major splice donor and translation initiation sites are
      sequestered by long-range base pairing and guanosines essential for both
      packaging and high-affinity binding to the cognate Gag protein are exposed in
      helical junctions. The structure reveals how translation is attenuated, Gag
      binding promoted, and unspliced dimeric genomes selected, by the RNA conformer
      that directs packaging. 

PMID- 25999510
TI  - Playing the field.

PMID- 25999509
TI  - Evolution. Systematic humanization of yeast genes reveals conserved functions and
      genetic modularity.
AB  - To determine whether genes retain ancestral functions over a billion years of
      evolution and to identify principles of deep evolutionary divergence, we replaced
      414 essential yeast genes with their human orthologs, assaying for
      complementation of lethal growth defects upon loss of the yeast genes. Nearly
      half (47%) of the yeast genes could be successfully humanized. Sequence
      similarity and expression only partly predicted replaceability. Instead,
      replaceability depended strongly on gene modules: Genes in the same process
      tended to be similarly replaceable (e.g., sterol biosynthesis) or not (e.g., DNA
      replication initiation). Simulations confirmed that selection for specific
      function can maintain replaceability despite extensive sequence divergence.
      Critical ancestral functions of many essential genes are thus retained in a
      pathway-specific manner, resilient to drift in sequences, splicing, and protein
      interfaces. 

PMID- 25999511
TI  - Erratum for the report "Mutation rate and genotype variation of Ebola virus from
      Mali case sequences" by T. Hoenen, D. Safronetz, A. Groseth, K. R. Wollenberg, O.
      A. Koita, B. Diarra, I. S. Fall, F. C. Haidara, F. Diallo, M. Sanogo, Y. S.
      Sarro, A. Kone, A. C. G. Togo, A. Traore, M. Kodio, A. Dosseh, K. Rosenke, E. de
      Wit, F. Feldmann, H. Ebihara, V. J. Munster, K. C. Zoon, H. Feldmann, S. Sow.

PMID- 25999512
TI  - Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology.
AB  - Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the
      phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not
      express acquired antigen receptors or undergo clonal selection and expansion when
      stimulated. Instead, ILCs react promptly to signals from infected or injured
      tissues and produce an array of secreted proteins termed cytokines that direct
      the developing immune response into one that is adapted to the original insult.
      The complex cross-talk between microenvironment, ILCs, and adaptive immunity
      remains to be fully deciphered. Only by understanding these complex regulatory
      networks can the power of ILCs be controlled or unleashed in order to regulate or
      enhance immune responses in disease prevention and therapy. 

PMID- 25999513
TI  - Ocean plankton. Structure and function of the global ocean microbiome.
AB  - Microbes are dominant drivers of biogeochemical processes, yet drawing a global
      picture of functional diversity, microbial community structure, and their
      ecological determinants remains a grand challenge. We analyzed 7.2 terabases of
      metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and
      mesopelagic waters across the globe to generate an ocean microbial reference gene
      catalog with >40 million nonredundant, mostly novel sequences from viruses,
      prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples,
      containing >35,000 species, we show vertical stratification with epipelagic
      community composition mostly driven by temperature rather than other
      environmental factors or geography. We identify ocean microbial core
      functionality and reveal that >73% of its abundance is shared with the human gut
      microbiome despite the physicochemical differences between these two ecosystems. 

PMID- 25999514
TI  - Ocean plankton. Environmental characteristics of Agulhas rings affect interocean
      plankton transport.
AB  - Agulhas rings provide the principal route for ocean waters to circulate from the
      Indo-Pacific to the Atlantic basin. Their influence on global ocean circulation
      is well known, but their role in plankton transport is largely unexplored. We
      show that, although the coarse taxonomic structure of plankton communities is
      continuous across the Agulhas choke point, South Atlantic plankton diversity is
      altered compared with Indian Ocean source populations. Modeling and in situ
      sampling of a young Agulhas ring indicate that strong vertical mixing drives
      complex nitrogen cycling, shaping community metabolism and biogeochemical
      signatures as the ring and associated plankton transit westward. The peculiar
      local environment inside Agulhas rings may provide a selective mechanism
      contributing to the limited dispersal of Indian Ocean plankton populations into
      the Atlantic. 

PMID- 25999515
TI  - Ocean plankton. Patterns and ecological drivers of ocean viral communities.
AB  - Viruses influence ecosystems by modulating microbial population size, diversity,
      metabolic outputs, and gene flow. Here, we use quantitative double-stranded DNA
      (dsDNA) viral-fraction metagenomes (viromes) and whole viral community
      morphological data sets from 43 Tara Oceans expedition samples to assess viral
      community patterns and structure in the upper ocean. Protein cluster cataloging
      defined pelagic upper-ocean viral community pan and core gene sets and suggested
      that this sequence space is well-sampled. Analyses of viral protein clusters,
      populations, and morphology revealed biogeographic patterns whereby viral
      communities were passively transported on oceanic currents and locally structured
      by environmental conditions that affect host community structure. Together, these
      investigations establish a global ocean dsDNA viromic data set with analyses
      supporting the seed-bank hypothesis to explain how oceanic viral communities
      maintain high local diversity. 

PMID- 25999517
TI  - Ocean plankton. Determinants of community structure in the global plankton
      interactome.
AB  - Species interaction networks are shaped by abiotic and biotic factors. Here, as
      part of the Tara Oceans project, we studied the photic zone interactome using
      environmental factors and organismal abundance profiles and found that
      environmental factors are incomplete predictors of community structure. We found
      associations across plankton functional types and phylogenetic groups to be
      nonrandomly distributed on the network and driven by both local and global
      patterns. We identified interactions among grazers, primary producers, viruses,
      and (mainly parasitic) symbionts and validated network-generated hypotheses using
      microscopy to confirm symbiotic relationships. We have thus provided a resource
      to support further research on ocean food webs and integrating biological
      components into ocean models. 

PMID- 25999516
TI  - Ocean plankton. Eukaryotic plankton diversity in the sunlit ocean.
AB  - Marine plankton support global biological and geochemical processes. Surveys of
      their biodiversity have hitherto been geographically restricted and have not
      accounted for the full range of plankton size. We assessed eukaryotic diversity
      from 334 size-fractionated photic-zone plankton communities collected across
      tropical and temperate oceans during the circumglobal Tara Oceans expedition. We
      analyzed 18S ribosomal DNA sequences across the intermediate plankton-size
      spectrum from the smallest unicellular eukaryotes (protists, >0.8 micrometers) to
      small animals of a few millimeters. Eukaryotic ribosomal diversity saturated at
      ~150,000 operational taxonomic units, about one-third of which could not be
      assigned to known eukaryotic groups. Diversity emerged at all taxonomic levels,
      both within the groups comprising the ~11,200 cataloged morphospecies of
      eukaryotic plankton and among twice as many other deep-branching lineages of
      unappreciated importance in plankton ecology studies. Most eukaryotic plankton
      biodiversity belonged to heterotrophic protistan groups, particularly those known
      to be parasites or symbiotic hosts. 

PMID- 25999519
TI  - High-Throughput Screening to Identify Compounds That Increase Fragile X Mental
      Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X
      Syndrome Patient-Derived Induced Pluripotent Stem Cells.
AB  - : Fragile X syndrome (FXS), the most common form of inherited cognitive
      disability, is caused by a deficiency of the fragile X mental retardation protein
      (FMRP). In most patients, the absence of FMRP is due to an aberrant
      transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS
      has no cure, and the available treatments only provide symptomatic relief. Given
      that FMR1 gene silencing in FXS patient cells can be partially reversed by
      treatment with compounds that target repressive epigenetic marks, restoring FMRP
      expression could be one approach for the treatment of FXS. We describe a
      homogeneous and highly sensitive time-resolved fluorescence resonance energy
      transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem
      cells differentiated from an FXS patient-derived induced pluripotent stem cell
      (iPSC) line that does not express any FMRP, we screened a collection of
      approximately 5,000 known tool compounds and approved drugs using this FMRP assay
      and identified 6 compounds that modestly increase FMR1 gene expression in FXS
      patient cells. Although none of these compounds resulted in clinically relevant
      levels of FMR1 mRNA, our data provide proof of principle that this assay combined
      with FXS patient-derived neural stem cells can be used in a high-throughput
      format to identify better lead compounds for FXS drug development. SIGNIFICANCE:
      In this study, a specific and sensitive fluorescence resonance energy transfer
      based assay for fragile X mental retardation protein detection was developed and
      optimized for high-throughput screening (HTS) of compound libraries using fragile
      X syndrome (FXS) patient-derived neural stem cells. The data suggest that this
      HTS format will be useful for the identification of better lead compounds for
      developing new therapeutics for FXS. This assay can also be adapted for FMRP
      detection in clinical and research settings.

PMID- 25999518
TI  - Study of Bone Marrow and Embryonic Stem Cell-Derived Human Mesenchymal Stem Cells
      for Treatment of Escherichia coli Endotoxin-Induced Acute Lung Injury in Mice.
AB  - : Mesenchymal stem cells (MSCs) can be derived from multiple tissue sources.
      However, the optimal source of MSCs for cell-based therapy for acute lung injury
      (ALI) is unclear. In the present experiments, we studied bone marrow (BM)-derived
      and embryonic stem cell-derived human MSC (ES-MSCs) as a therapeutic agent in
      Escherichia coli endotoxin-induced ALI in mice. We hypothesized that ES-MSCs
      would be more potent than BM-MSCs owing to its more primitive source of origin.
      ALI was induced by the intratracheal instillation of endotoxin at 4 mg/kg into 10
      12-week-old C57BL/6 mice with or without BM-MSCs, ES-MSCs, or normal human lung
      fibroblasts as a cellular control. Compared with the endotoxin-injured mice at 48
      hours, the administration of ES-MSCs provided results similar to those of BM
      MSCs, significantly reducing the influx of white blood cells and neutrophils and
      decreasing the secretion of the inflammatory cytokines, macrophage inflammatory
      protein-2 and tumor necrosis factor-alpha, in the injured alveolus. BM-MSCs also
      reduced extravascular lung water, a measure of pulmonary edema, by 60% and the
      total protein levels, a measure of lung permeability, by 66%. However,
      surprisingly, ES-MSCs did not have these protective effects, which was partially
      explained by the increased secretion of matrix metallopeptidase 9 by ES-MSCs, an
      enzyme known to increase lung protein permeability. In conclusion, both BM-MSCs
      and ES-MSCs markedly decreased endotoxin-induced inflammation. However, ES-MSCs
      did not show any beneficial effect on reducing pulmonary edema and lung protein
      permeability compared with BM-MSCs, suggesting that not all MSCs behave in a
      similar fashion. Our results highlight the need perhaps for a disease-specific
      potency assay for MSCs. SIGNIFICANCE: To determine the optimal source of
      mesenchymal stem cells (MSCs) for cell-based therapy for acute lung injury, bone
      marrow (BM)- and embryonic stem cell-derived human MSC (ES-MSCs) were compared as
      therapeutic agents for Escherichia coli endotoxin-induced lung injury in mice. ES
      MSCs behaved similarly to BM-MSCs by markedly decreasing the inflammatory
      response induced by endotoxin. However, unlike BM-MSCs, ES-MSCs provided no
      protective effects against increasing lung water and protein permeability, in
      part because of an increase in expression of matrix metallopeptidase 9 by ES
      MSCs. In patients with acute respiratory distress syndrome, impaired alveolar
      fluid clearance (i.e., no resolution of pulmonary edema fluid) has been
      associated with higher mortality rates. Although ES-MSCs might ultimately be
      found to have properties superior to those of BM-MSCs, such as for
      immunomodulation, these results highlight the need for a disease-specific potency
      assay for stem cell-based therapy.

PMID- 25999520
TI  - Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.
AB  - : Chronic rotator cuff (RC) tears are a common and debilitating injury,
      characterized by dramatic expansion of adipose tissue, muscle atrophy, and
      limited functional recovery. The role of adipose expansion in RC pathology is
      unknown; however, given the identified paracrine/endocrine regulation by other
      adipose depots, it likely affects tissue function outside its boundaries.
      Therefore, we characterized the epimuscular (EM) fat depot of the human rotator
      cuff, defined its response to RC tears, and evaluated its influence on myogenesis
      in vitro. EM fat biopsies exhibited morphological and functional features of
      human beige fat compared with patient-matched s.c. biopsies, which appeared
      whiter. The transcriptional profile of EM fat and isolated EM adipose-derived
      stem cells (ASCs) shifted as a function of the tear state; EM fat from intact
      cuffs had significantly elevated expression of the genes associated with
      uncoupled respiration, and the EM fat from torn cuffs had increased expression of
      beige-selective genes. EM ASC cocultures with human- and mouse-derived myogenic
      cells exhibited increased levels of myogenesis compared with s.c. cultures.
      Increased fusion and decreased proliferation of myogenic cells, rather than
      changes to the ASCs, were found to underlie this effect. Taken together, these
      data suggest that EM fat in the human rotator cuff is a novel beige adipose depot
      influenced by cuff state with therapeutic potential for promoting myogenesis in
      neighboring musculature. SIGNIFICANCE: Rotator cuff tears affect millions of
      people in the U.S.; however, current interventions are hindered by persistent
      muscle degeneration. This study identifies the therapeutic potential for muscle
      recovery in the epimuscular fat in the rotator cuff, previously considered a
      negative feature of the pathology, and finds that this fat is beige, rather than
      white. This is important for two reasons. First, the stem cells that were
      isolated from this beige fat are more myogenic than those from white fat, which
      have been the focus of stem cell-based therapies to date, suggesting epimuscular
      fat could be a better stem cell source to augment rotator cuff repair. Second,
      these beige stem cells promote myogenesis in neighboring cells in culture,
      suggesting the potential for this fat to be manipulated therapeutically to
      promote muscle recovery through secreted signals.

PMID- 25999521
TI  - Seroprevalence of 10 human papillomavirus types in the general rural population
      of Anyang, China: a cross-sectional study.
AB  - OBJECTIVES: Data on the seroprevalence of human papillomavirus (HPV) in China are
      limited. The objective of this study was to characterise the serological profiles
      of HPV infection in a rural Chinese population and help establish effective
      vaccine policy. METHODS: Serum antibodies against the major capsid protein L1 of
      10 HPV types (HPV-3, 6, 11, 16, 18, 45, 52, 57, 58 and 75) were evaluated with
      Luminex-based multiplex serology in a population-based study of 5548 adults
      (including 1587 couples) aged 25-65 years enrolled from rural Anyang, China, in
      2007-2009. RESULTS: The seroprevalence for any HPV type and any of the types HPV
      6/11/16/18 was 64.8% and 34.4%, respectively. 30.3% of adults were seropositive
      for any mucosal high-risk (HR) HPV, and HPV-58 (10.6%), HPV-16 (9.7%) and HPV-18
      (9.3%) were the three most common types. 24.8% of seropositive individuals were
      positive for multiple mucosal HR-HPV serotypes. Seroprevalence for most HPV types
      was similar among men and women. While mucosal low-risk HPV seropositivity was
      found to significantly decrease with age, the prevalence of antibodies to mucosal
      HR antigens showed a general trend of increase with age. The lifetime number of
      sex partners was independently associated with mucosal HR-HPV seropositivity.
      Positive correlation of spousal seropositivity was observed for mucosal HPV but
      not for cutaneous HPV. CONCLUSIONS: HPV infection was common in both men and
      women in rural China. HPV seroprevalence differed significantly with age, sexual
      behaviour and spousal infection status. These findings will be useful for
      evaluating and establishing HPV vaccination programmes.

PMID- 25999522
TI  - Delayed awareness of clinically significant test results on hospital services
      without an automated alert system.

PMID- 25999523
TI  - Psychometric Evaluation of an Instrument for Measuring Organizational Climate for
      Quality: Evidence From a National Sample of Infection Preventionists.
AB  - In recent years, there has been increased interest in measuring the climate for
      infection prevention; however, reliable and valid instruments are lacking. This
      study tested the psychometric properties of the Leading a Culture of Quality for
      Infection Prevention (LCQ-IP) instrument measuring the infection prevention
      climate in a sample of 972 infection preventionists from acute care hospitals. An
      exploratory principal component analysis showed that the instrument had
      structural validity and captured 4 factors related to the climate for infection
      prevention: Psychological Safety, Prioritization of Quality, Supportive Work
      Environment, and Improvement Orientation. LCQ-IP exhibited excellent internal
      consistency, with a Cronbach alpha of .926. Criterion validity was supported with
      overall LCQ-IP scores, increasing with the number of evidence-based prevention
      policies in place (P = .047). This psychometrically sound instrument may be
      helpful to researchers and providers in assessing climate for quality related to
      infection prevention.

PMID- 25999524
TI  - Developmental typologies of serious mental illness and violence: Evidence from a
      forensic psychiatric setting.
AB  - OBJECTIVE: To identify subgroups of forensic psychiatric patients based on the
      age onset of serious mental illness and offending and assess the external
      validity of the subgroups with theoretically based sociodemographic, clinical,
      legal and risk-related variables. METHOD: The age onset of serious mental illness
      and criminal contact was ascertained for a sample of 232 patients. A range of
      sociodemographic, clinical, legal and risk-related variables were coded to assess
      whether age onset subgroups differed in a manner consistent with the literature
      on typologies of mentally ill offenders. RESULTS: One-quarter of the sample was
      classified as early starters (patients whose first offense occurred before
      becoming mentally ill), while two-thirds were late starters (where first offense
      occurred following illness onset). A small percentage (8%) of patients were
      deemed late late starters, defined as late starters who had experienced 10+ years
      of illness and were >37 years upon first arrest. A larger proportion of early
      starters had a substance use disorder, antisocial personality disorder and a
      greater number of static/historical risk factors for violence. Early starters
      were younger upon first arrest and had more previous criminal contacts compared
      to late starters and late late starters. Mental illness was found to start later
      in life for late late starters; this group was also more likely to have been
      married and to have a spouse as victim in the index offense. CONCLUSION: We found
      support for distinct subgroups of mentally ill offenders based on the age onset
      of illness and criminal contact. Compared to late starters, offenses committed by
      early starters may be motivated more frequently by antisocial lifestyle and
      attitudes, as well as more instrumental behaviors related to substance abuse. In
      addition, late late starters may represent a distinct third subgroup within late
      starters, characterized by relatively higher levels of functioning and social
      stability; future work should replicate. Findings suggest different
      rehabilitation needs of the subgroups.

PMID- 25999525
TI  - Lifting the burden of bipolar disorder: The role of psychotherapies.

PMID- 25999526
TI  - Childhood predictors of lifetime suicide attempts and non-suicidal self-injury in
      depressed adults.
AB  - OBJECTIVE: Adverse childhood experiences are well-recognized risk factors for a
      variety of mental health issues, including depression, suicide attempts and non
      suicidal self-injury. However, less is known about whether childhood adversity,
      in the form of low parental care, overprotection and abuse, is associated with
      suicide attempt and non-suicidal self-injury within a sample of depressed adults.
      METHOD: The sample of outpatients (n = 372) was drawn from two randomized
      depression trials. Childhood adversity variables, depression severity, age of
      first depressive episode (major depression episode onset), lifetime suicide
      attempt and non-suicidal self-injury were recorded at baseline. The association
      between variables and outcome measures was examined using partial correlations,
      univariate and multivariate logistic regressions. RESULTS: Low maternal care was
      significantly associated with suicide attempt; low paternal care was associated
      with non-suicidal self-injury; overprotection was not associated with either
      outcome. Other risk factors for suicide attempt were major depression episode
      onset and baseline depression severity. Major depression episode onset was also a
      risk factor for non-suicidal self-injury. Abuse, regardless of how it was
      measured, was not significantly associated with either behaviour after adjusting
      for its correlations with low maternal or paternal care. CONCLUSION: In this
      sample of depressed adults, the quality of ongoing, intra-familial relationships,
      as measured by levels of parental care, had a greater impact on suicide attempt
      and non-suicidal self-injury than abuse. As the findings were not a priori
      hypotheses, they require replication. Although the cross-sectional study design
      limits causal determination, the findings suggest different childhood risk
      factors for suicide attempt and non-suicidal self-injury and underscore the
      impact of low parental care on these two behaviours. These findings signal to
      clinicians the importance of asking specifically about suicide attempts, and non
      suicidal self-injury, as well as levels of parental care in childhood. When
      endorsed, low parental care may be considered an important factor in
      contextualizing a patient's depression and potential risk for suicide and non
      suicidal self-injury.

PMID- 25999527
TI  - Commentary on: Incidence of eating disorders in Danish psychiatric secondary
      healthcare 1970-2008.

PMID- 25999531
TI  - Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?
AB  - Obesity and associated insulin resistance predispose individuals to develop
      chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease.
      Although these disorders affect a significant proportion of the global
      population, the underlying mechanisms of disease remain poorly understood. The
      discovery of elevated tumor necrosis factor-alpha in adipose tissue as an inducer
      of obesity-associated insulin resistance marked a new era of understanding that a
      subclinical inflammatory process underlies the insulin resistance and metabolic
      dysfunction that precedes type 2 diabetes. Advances in the field identified
      components of both the innate and adaptive immune response as key players in
      regulating such inflammatory processes. As antigen specificity is a hallmark of
      an adaptive immune response, its role in modulating the chronic inflammation that
      accompanies obesity and type 2 diabetes begs the question of whether insulin
      resistance and type 2 diabetes can have autoimmune components. In this
      Perspective, we summarize current data that pertain to the activation and
      perpetuation of adaptive immune responses during obesity and discuss key missing
      links and potential mechanisms for obesity-related insulin resistance and type 2
      diabetes to be considered as potential autoimmune diseases.

PMID- 25999532
TI  - The missing link: studying the alternative TGF-beta pathway provides a unifying
      theory for different components of diabetic nephropathy.

PMID- 25999530
TI  - Human beta-cell proliferation and intracellular signaling: part 3.
AB  - This is the third in a series of Perspectives on intracellular signaling pathways
      coupled to proliferation in pancreatic beta-cells. We contrast the large
      knowledge base in rodent beta-cells with the more limited human database. With
      the increasing incidence of type 1 diabetes and the recognition that type 2
      diabetes is also due in part to a deficiency of functioning beta-cells, there is
      great urgency to identify therapeutic approaches to expand human beta-cell
      numbers. Therapeutic approaches might include stem cell differentiation,
      transdifferentiation, or expansion of cadaver islets or residual endogenous beta
      cells. In these Perspectives, we focus on beta-cell proliferation. Past
      Perspectives reviewed fundamental cell cycle regulation and its upstream
      regulation by insulin/IGF signaling via phosphatidylinositol-3 kinase/mammalian
      target of rapamycin signaling, glucose, glycogen synthase kinase-3 and liver
      kinase B1, protein kinase Czeta, calcium-calcineurin-nuclear factor of activated
      T cells, epidermal growth factor/platelet-derived growth factor family members,
      Wnt/beta-catenin, leptin, and estrogen and progesterone. Here, we emphasize Janus
      kinase/signal transducers and activators of transcription, Ras/Raf/extracellular
      signal-related kinase, cadherins and integrins, G-protein-coupled receptors, and
      transforming growth factor beta signaling. We hope these three Perspectives will
      serve to introduce these pathways to new researchers and will encourage
      additional investigators to focus on understanding how to harness key
      intracellular signaling pathways for therapeutic human beta-cell regeneration for
      diabetes.

PMID- 25999533
TI  - AMPK-TBC1D4-dependent mechanism for increasing insulin sensitivity of skeletal
      muscle.

PMID- 25999534
TI  - Role of perivascular adipose tissue on vascular reactive oxygen species in type 2
      diabetes: a give-and-take relationship.

PMID- 25999535
TI  - Pleiotropic benefits of metformin: macrophage targeting its anti-inflammatory
      mechanisms.

PMID- 25999536
TI  - Bleach in the diabetic kidney destabilizes basement membrane collagen.

PMID- 25999537
TI  - Therapeutic window of interleukin-2 for autoimmune diseases.

PMID- 25999539
TI  - Comment on Smith et al. Protein ingestion induces muscle insulin resistance
      independent of leucine-mediated mTOR activation. Diabetes 2015;64:1555-1563.

PMID- 25999540
TI  - Response to Comment on Smith et al. Protein ingestion induces muscle insulin
      resistance independent of leucine-mediated mTOR activation. Diabetes 2015;64:1555
      1563.

PMID- 25999541
TI  - Comment on Chondronikola et al. Brown adipose tissue improves whole-body glucose
      homeostasis and insulin sensitivity in humans. Diabetes 2014;63:4089-4099.

PMID- 25999542
TI  - Response to comment on Chondronikola et al. Brown adipose tissue improves whole
      body glucose homeostasis and insulin sensitivity in humans. Diabetes 2014;63:4089
      4099.

PMID- 25999543
TI  - Comment on Gray et al. Insulin regulates brain function, but how does it get
      there? Diabetes 2014;63:3992-3997.

PMID- 25999544
TI  - Comment on Heni et al. Central insulin administration improves whole-body insulin
      sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes
      2014;63:4083-4088.

PMID- 25999545
TI  - Response to Comment on Heni et al. Central insulin administration improves whole
      body insulin sensitivity via hypothalamus and parasympathetic outputs in men.
      Diabetes 2014;63:4083-4088.

PMID- 25999546
TI  - Massively parallel DNA sequencing successfully identified seven families with
      deafness-associated MYO6 mutations: the mutational spectrum and clinical
      characteristics.
AB  - OBJECTIVES: To elucidate the involvement of MYO6 mutations, known to be
      responsible for DFNA22/DFNB37, in Japanese hearing loss patients through the use
      of genetic analysis. METHODS: Genomic variations responsible for hearing loss
      were identified by massively parallel DNA sequencing (MPS) of 63 target candidate
      genes in 1120 Japanese hearing loss patients, and the detailed clinical features
      for the patients with MYO6 mutations were collected and analyzed. RESULTS: Four
      mutations were successfully found in 7 families exhibiting autosomal dominant
      inheritance. All of the patients showed progressive hearing loss, but hearing
      type and onset age varied. Further, none of the affected patients showed any
      associated symptoms, such as hypertrophic cardiomyopathy or retinitis pigmentosa.
      CONCLUSIONS: MPS is powerful tool for the identification of rare causative
      deafness gene mutations, such as MYO6. The clinical characteristics noted in the
      present study not only confirmed the findings of previous reports but provided
      important new clinical information.

PMID- 25999547
TI  - Molecular diagnosis of deafness-a preface.

PMID- 25999548
TI  - Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: their origin and a
      literature review.
AB  - OBJECTIVE: The mutation spectrum of the GJB2 and SLC26A4 genes, the 2 most common
      genes causing deafness, are known to be ethnic specific. In this study, the
      spectrum of the reported GJB2 and SLC26A4 mutations in different populations are
      reviewed and considered from a human migration perspective. METHODS: Fifty-two
      and 17 articles on GJB2 and SLC26A4 mutations, respectively, were reviewed
      through the PubMed database from April 1996 to September 2014. The 4 most
      prevalent mutations were selected and compared. A cluster analysis was
      subsequently performed for these selected mutations. RESULTS: The present review
      of frequent mutations shows the ethnic-specific GJB2 and SLC26A4 gene mutation
      spectrum. A cluster analysis of the GJB2 and SLC26A4 genes revealed similarities
      between ethnic populations. CONCLUSION: The mutation spectrum reviewed in this
      study clearly indicated that the frequent mutations in the GJB2 and SLC26A4 genes
      are consistent with the founder mutation hypothesis. A comparison with the Y
      chromosome phylogenetic tree indicated that these mutations may have occurred
      during human migration.

PMID- 25999549
TI  - Draft Genome Sequence of a Sulfur-Oxidizing Autotroph, Sulfuricella sp. Strain
      T08, Isolated from a Freshwater Lake.
AB  - Sulfuricella sp. strain T08 is a sulfur-oxidizing autotroph newly isolated from a
      freshwater lake in Japan. Strain T08 is the second isolate of the genus
      Sulfuricella. Here, we report the annotated draft genome sequence of the isolate.

PMID- 25999550
TI  - Draft Genome Sequence of a Drug-Susceptible New Zealand Isolate of Mycobacterium
      tuberculosis Lineage 3.
AB  - We report here the draft whole-genome sequence of a drug-susceptible lineage 3
      (East-African Indian) isolate of Mycobacterium tuberculosis from New Zealand
      (NZ3DS1) and compare it to a multidrug-resistant lineage 3 isolate (NZ3MDR1) with
      an identical 24-locus mycobacterial interspersed repetitive-unit-variable-number
      tandem-repeat profile. 

PMID- 25999551
TI  - Complete genome sequence of a porcine epidemic diarrhea virus from a novel
      outbreak in belgium, january 2015.
AB  - Porcine epidemic diarrhea virus (PEDV) is a member of the family Coronaviridae
      and can cause severe outbreaks of diarrhea in piglets from different age groups.
      Here, we report the complete genome sequence (28,028 nt) of a PEDV strain
      isolated during a novel outbreak in Belgium. 

PMID- 25999552
TI  - Draft genome sequences of 18 oral streptococcus strains that encode amylase
      binding proteins.
AB  - A number of commensal oral streptococcal species produce a heterogeneous group of
      proteins that mediate binding of salivary alpha-amylase. This interaction likely
      influences streptococcal colonization of the oral cavity. Here, we present draft
      genome sequences of several strains of oral streptococcal species that bind human
      salivary amylase. 

PMID- 25999553
TI  - Draft Genome Sequence of Mycobacterium bovis Strain SP38, a Pathogenic Bacterium
      Isolated from a Bovine in Brazil.
AB  - We report a draft genome sequence of Mycobacterium bovis strain SP38, isolated
      from the lungs of a cow in Brazil. The assembly of reads resulted in 36 contigs
      in a total of approximately 4.37 Mb. Comparison of M. bovis strains sequenced to
      date will aid in understanding bovine tuberculosis in Brazil. 

PMID- 25999554
TI  - Draft Genome Sequence of Jeotgalibacillus soli DSM 23228, a Bacterium Isolated
      from Alkaline Sandy Soil.
AB  - Jeotgalibacillus soli, a bacterium capable of degrading N-acyl homoserine
      lactone, was isolated from a soil sample in Portugal. J. soli constitutes the
      only Jeotgalibacillus species isolated from a non-marine source. Here, the draft
      genome, several interesting glycosyl hydrolases, and its putative N-acyl
      homoserine lactonases are presented. 

PMID- 25999555
TI  - Draft Genome Sequence of New Leprosy Agent Mycobacterium lepromatosis.
AB  - Mycobacterium lepromatosis is a newly discovered cause of leprosy. Here, we
      present a near-complete genome of M. lepromatosis from strain FJ924 obtained from
      a patient who died of leprosy. The genome contained 3,215,823 nucleotides and
      matched ~87% with the Mycobacterium leprae genome. This genome is likely the
      smallest of all mycobacterial genomes known to date. 

PMID- 25999556
TI  - Genome Assemblies of Three Soil-Associated Devosia species: D. insulae, D. limi,
      and D. soli.
AB  - Agricultural soils constitute highly diverse ecosystems with very rich bacterial
      populations. Recent studies employing next-generation sequencing techniques have
      begun to explore the dynamics of bacterial species of such soils and utilized
      metagenomics approaches to understand how the diversity in soil microorganisms is
      affected or modified by agricultural practices. Understanding any microorganism's
      environmental adaptability in the genomic era starts by fully appreciating their
      encoding genome. Here, we report the draft genome sequences of three Devosia
      species based on three type strains that originated from soil samples: D. insulae
      strain DS-56, D. limi strain DSM17137, and D. soli strain GH2-10. 

PMID- 25999557
TI  - Draft Genome Sequence of Pseudomonas aeruginosa KF702 (NBRC 110665), a
      Polychlorinated Biphenyl-Degrading Bacterium Isolated from Biphenyl-Contaminated
      Soil.
AB  - Pseudomonas aeruginosa KF702 (NBRC 110665) utilizes biphenyl as a sole source of
      carbon and degrades polychlorinated biphenyls (PCBs). Here, we report the
      7,167,540-bp draft genome sequence of KF702, which contains 6,714 coding
      sequences and a 65.8 mol% G+C content. The strain possesses genes for biphenyl
      catabolism and other genes that mediate degradation of various aromatic
      compounds. 

PMID- 25999558
TI  - Complete Genome Sequence of Pseudomonas aeruginosa Strain 8380, Isolated from the
      Human Gut.
AB  - Pseudomonas aeruginosa shows multidrug resistance, which is mainly attributable
      to its expression of xenobiotic efflux pumps. However, it is unclear how silent
      pumps are expressed in clinical isolates. Here, we sequenced the complete genome
      of P. aeruginosa strain 8380, which was isolated from a human gut. 

PMID- 25999559
TI  - Draft Genome Sequence of Aeromonas caviae 8LM, Isolated from Stool Culture of a
      Child with Diarrhea.
AB  - Aeromonas spp. are Gram-negative rods ubiquitous in aquatic environments;
      however, some species are able to cause a variety of infections in humans. Here,
      we report the draft genome sequence of Aeromonas caviae 8LM isolated from stool
      culture from a child with diarrhea in southern Brazil. 

PMID- 25999560
TI  - Draft Genome Sequences of Corynebacterium kroppenstedtii CNM633/14 and CNM632/14,
      Multidrug-Resistant and Antibiotic-Sensitive Isolates from Nodules of
      Granulomatous Mastitis Patients.
AB  - Corynebacterium kroppenstedtii has been associated with infections of the female
      breast. Genome sequencing of two strains revealed a specific genomic island in
      the multidrug-resistant isolate CNM633/14 with similarity to the R plasmid
      pJA144188 of Corynebacterium resistens DSM 45100, being indicative of the
      horizontal transfer of antibiotic resistance genes to C. kroppenstedtii. 

PMID- 25999561
TI  - Draft Genome Sequence of Catabacter hongkongensis Type Strain HKU16T, Isolated
      from a Patient with Bacteremia and Intestinal Obstruction.
AB  - We report the draft genome sequence of Catabacter hongkongensis, a catalase
      positive bacterium which causes bacteremia with high mortality. The 3.2-Mb genome
      contains 3,161 protein coding sequences, including putative catalase and motility
      related proteins, and antibiotic resistance genes, which could be important for
      its virulence and adaptation to diverse environments. 

PMID- 25999562
TI  - Complete Genome Sequence of Bacillus subtilis Strain ATCC 6051a, a Potential Host
      for High-Level Secretion of Industrial Enzymes.
AB  - Bacillus subtilis ATCC 6051a (=KCTC 1028), which is less domesticated than strain
      168, is widely used for the secretory expression of industrial enzymes. Herein,
      we present the complete genome sequence of the Bacillus subtilis strain ATCC
      6051a. 

PMID- 25999563
TI  - Genome Sequence of Penicillium capsulatum Strain ATCC 48735, a Rare Penicillium
      Species Used in Paper Manufactories but That Recently Caused Invasive Infection.
AB  - The genus Penicillium phylogenetically belongs to Trichocomaceae, with
      approximately 300 reported species. The majority of these species are saprobic
      and commonly occur in soil. This paper reports the genome sequence of Penicillium
      capsulatum strain ATCC 48735, a rare Penicillium species used in paper
      manufactories and that was recently reported as a human-invasive opportunist. 

PMID- 25999564
TI  - Complete Genome Sequence of a Pathogenic Genotype 1 Subtype 3 Porcine
      Reproductive and Respiratory Syndrome Virus (Strain SU1-Bel) from Pig Primary
      Tissue.
AB  - We report here the complete genome of the pathogenic eastern European subtype 3
      porcine reproductive and respiratory syndrome virus (PRRSV) strain SU1-Bel,
      sequenced directly from a pig lymph node. While sharing substantial sequence
      similarity with other subtype 3 strains, SU1-Bel is found to harbor unique indels
      and contain putative novel subgenomic RNAs. 

PMID- 25999565
TI  - Draft Genome Sequence of Rhodococcus sp. Strain 311R.
AB  - Here, we report the draft genome sequence of Rhodococcus sp. strain 311R, which
      was isolated from a site contaminated with alkanes and aromatic compounds. Strain
      311R shares 90% of the genome of Rhodococcus erythropolis SK121, which is the
      closest related bacteria. 

PMID- 25999566
TI  - Genome Sequence of Leucobacter sp. 4J7B1, a Plant-Osmoprotectant Soil
      Microorganism.
AB  - We report the first genome sequence for Leucobacter sp. 4J7B1, a newly described
      desiccation-tolerant strain. The complete genome sequence of Leucobacter sp.
      4J7B1 has been sequenced and is estimated to be around 3.5 Mb in size, with an
      average GC content of 62.18%. We predict 2,953 protein-coding sequences. 

PMID- 25999567
TI  - Draft Genome Sequence of a Papaverine-Degrading, Gram-positive Arthrobacter sp.,
      Isolated from Soil Near Hohenheim, Germany.
AB  - We present the 4.8-Mb draft genome of a soil bacterium identified as Arthrobacter
      sp. This Gram-positive soil bacterium is able to use the aromatic compound
      papaverine as sole carbon source and will be examined for novel oxygenases. 

PMID- 25999568
TI  - Draft Genome Sequence of Sporidiobolus salmonicolor CBS 6832, a Red-Pigmented
      Basidiomycetous Yeast.
AB  - We report the genome sequencing and annotation of the basidiomycetous red
      pigmented yeast Sporidiobolus salmonicolor strain CBS 6832. The current assembly
      contains 395 scaffolds, for a total size of about 20.5 Mb and a G+C content of
      ~61.3%. The genome annotation predicts 5,147 putative protein-coding genes. 

PMID- 25999569
TI  - Near-Full-Length Genome Sequence of a Novel Reovirus from the Chinese Mitten
      Crab, Eriocheir sinensis.
AB  - A novel Eriocheir sinensis reovirus (EsRV) was identified using deep-sequencing
      techniques in crabs afflicted with trembling disease (TD). Near-full-length
      genome sequences of 12 segments of EsRV were obtained. The genome of EsRV will
      facilitate further studies on the causative agent of TD. 

PMID- 25999570
TI  - Genome Sequence of Lactococcus lactis subsp. cremoris Mast36, a Strain Isolated
      from Bovine Mastitis.
AB  - The genome sequence of Lactococcus lactis subsp. cremoris Mast36, isolated from
      bovine mastitis, is reported here. This strain was shown to be able to grow in
      milk and still possess genes of vegetable origin. The genome also contains a
      cluster of genes associated with pathogenicity. 

PMID- 25999571
TI  - Draft Whole-Genome Sequence of Morganella morganii Serotype O:1ab.
AB  - Morganella morganii is a facultative pathogen of humans, causing urinary tract
      and postsurgical infections. Here, we report a high-quality draft assembly of the
      O:1ab serotype. 

PMID- 25999572
TI  - Draft Genome Sequence of Chromobacterium vaccinii, a Potential Biocontrol Agent
      against Mosquito (Aedes aegypti) Larvae.
AB  - Chromobacterium vaccinii has been isolated only from cranberry bogs in
      Massachusetts. While it is unknown what role these bacteria play in their natural
      environments, they hold potential as biological control agents against the larvae
      of insect pests. Potential virulence genes were identified, including the
      violacein synthesis pathway, siderophores, and chitinases. 

PMID- 25999573
TI  - Complete Genome Sequence of Streptococcus thermophilus SMQ-301, a Model Strain
      for Phage-Host Interactions.
AB  - Streptococcus thermophilus is used by the dairy industry to manufacture yogurt
      and several cheeses. Using PacBio and Illumina platforms, we sequenced the genome
      of S. thermophilus SMQ-301, the host of several virulent phages. The genome is
      composed of 1,861,792 bp and contains 2,037 genes, 67 tRNAs, and 18 rRNAs. 

PMID- 25999574
TI  - Genome Sequence of Mycoplasma meleagridis Type Strain 17529.
AB  - Mycoplasma meleagridis is a prominent turkey bacterial pathogen associated with
      airsacculitis and reproductive disorders. Notwithstanding the economic losses
      caused by M. meleagridis, its genome has still not been sequenced. For a better
      understanding of its genetic background and pathogenicity mechanisms, we
      sequenced the genome of M. meleagridis type strain ATCC 25294. 

PMID- 25999575
TI  - Draft genome sequences of clostridium strains native to Colombia with the
      potential to produce solvents.
AB  - Genomes from four Clostridium sp. strains considered to be mesophilic anaerobic
      bacteria, isolated from crop soil in Colombia, with a strong potential to produce
      alcohols like 1,3-propanediol, were analyzed. We present the draft genome of
      these strains, which will be useful for developing genetic engineering
      strategies. 

PMID- 25999576
TI  - Full-length coding sequences for 12 bovine viral diarrhea virus isolates from
      persistently infected cattle in a feedyard in kansas.
AB  - We report here the full-length coding sequences of 12 bovine viral diarrhea virus
      (BVDV) isolates from persistently infected cattle in a feedyard in southwest KS.
      These 12 genomes represent the three major subtypes of BVDV (BVDV-1a, 1b, and 2a)
      currently circulating in the United States. 

PMID- 25999577
TI  - Genome Sequence of Anoxybacillus thermarum AF/04T, Isolated from the Euganean Hot
      Springs in Abano Terme, Italy.
AB  - Anoxybacillus thermarum AF/04(T) was isolated from the Euganean hot springs in
      Abano Terme, Italy. The present work reports a high-quality draft genome sequence
      of strain AF/04(T). This work also provides useful insights into glycoside
      hydrolases, glycoside transferases, and sugar transporters that may be involved
      in cellular carbohydrate metabolism. 

PMID- 25999578
TI  - Genome Sequence of Cronobacter sakazakii Serogroup O:4, Sequence Type 4 Strain
      CDC 2009-03746, Isolated from a Fatal Case of Infantile Meningitis.
AB  - We report the draft genome sequence of a Cronobacter sakazakii serogroup O:4,
      sequence type 4 strain, CDC 2009-03746 (=NM1240=2009-06-01), isolated from a
      fatal case of infantile meningitis. The draft genome has a size of 4,492,904 bp
      and a G+C% content of 56.7. 

PMID- 25999580
TI  - Genome Sequence of Bacillus coagulans P38, an Efficient Polymer-Grade l-Lactate
      Producer from Cellulosic Substrates.
AB  - Bacillus coagulans P38 is an efficient polymer-grade l-lactic acid producer from
      a cellulosic carbon source. Here, the draft 3.37-Mb genome sequence of this
      potential strain may provide useful information to further improve the strain
      performance for higher titers and, importantly, to understand the mechanism of
      its high tolerance for 2-furfural. 

PMID- 25999579
TI  - Complete Genome Sequence of Linezolid-Susceptible Staphylococcus haemolyticus
      Sh29/312/L2, a Clonal Derivative of a Linezolid-Resistant Clinical Strain.
AB  - We report the whole-genome sequence (WGS) of an in vitro susceptible derivative
      revertant mutant from a bloodstream isolate involved in a nosocomial outbreak in
      Brazil. The WGS comprises 2.5 Mb with 2,500 protein-coding sequences, 16rRNA
      genes, and 60 tRNA genes. 

PMID- 25999581
TI  - De novo genome assembly of grapevine yellow speckle viroid 1 from a grapevine
      transcriptome.
AB  - Grapevine yellow speckle viroid 1 (GYSVd1), which is a member of the genus
      Apscaviroid, causes yellow speckle disease in grapevines. Here, we report the
      complete de novo genome assembly of GYSVd1 from the grapevine transcriptome and
      identified 10 single nucleotide polymorphisms of GYSVd1 across the grapevine
      populations. 

PMID- 25999582
TI  - De novo genome assembly of ryegrass mosaic virus from a ryegrass transcriptome.
AB  - The ryegrass mosaic virus (RgMV) is a single positive-strand RNA virus belonging
      to the genus Rymovirus. The major natural hosts for RgMV are members of the
      Gramineae species, including ryegrass. Here, we report the nearly complete genome
      sequence of RgMV by de novo assembly using ryegrass transcriptomes. 

PMID- 25999583
TI  - Systematic Evaluation of Drosophila CRISPR Tools Reveals Safe and Robust
      Alternatives to Autonomous Gene Drives in Basic Research.
AB  - The Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR associated
      (CRISPR/Cas) technology allows rapid, site-specific genome modification in a wide
      variety of organisms . Proof-of-principle studies in Drosophila melanogaster have
      used various CRISPR/Cas tools and experimental designs, leading to significant
      uncertainty in the community about how to put this technology into practice.
      Moreover, it is unclear what proportion of genomic target sites can be modified
      with high efficiency. Here, we address these issues by systematically evaluating
      available CRISPR/Cas reagents and methods in Drosophila. Our findings allow
      evidence-based choices of Cas9 sources and strategies for generating knock-in
      alleles. We perform gene editing at a large number of target sites using a highly
      active Cas9 line and a collection of transgenic gRNA strains. The vast majority
      of target sites can be mutated with remarkable efficiency using these tools. We
      contrast our method to recently developed autonomous gene drive technology for
      somatic and germline genome engineering and conclude that optimized CRISPR with
      independent transgenes is as efficient, more versatile, and does not represent a
      biosafety risk. 

PMID- 25999584
TI  - Genome-Wide Analysis of Drosophila RBf2 Protein Highlights the Diversity of RB
      Family Targets and Possible Role in Regulation of Ribosome Biosynthesis.
AB  - RBf2 is a recently evolved retinoblastoma family member in Drosophila that
      differs from RBf1, especially in the C-terminus. To investigate whether the
      unique features of RBf2 contribute to diverse roles in gene regulation, we
      performed chromatin immunoprecipitation sequencing for both RBf2 and RBf1 in
      embryos. A previous model for RB-E2F interactions suggested that RBf1 binds dE2F1
      or dE2F2, whereas RBf2 is restricted to binding to dE2F2; however, we found that
      RBf2 targets approximately twice as many genes as RBf1. Highly enriched among the
      RBf2 targets were ribosomal protein genes. We tested the functional significance
      of this finding by assessing RBf activity on ribosomal protein promoters and the
      endogenous genes. RBf1 and RBf2 significantly repressed expression of some
      ribosomal protein genes, although not all bound genes showed transcriptional
      effects. Interestingly, many ribosomal protein genes are similarly targeted in
      human cells, indicating that these interactions may be relevant for control of
      ribosome biosynthesis and growth. We carried out bioinformatic analysis to
      investigate the basis for differential targeting by these two proteins and found
      that RBf2-specific promoters have distinct sequence motifs, suggesting unique
      targeting mechanisms. Association of RBf2 with these promoters appears to be
      independent of dE2F2/dDP, although promoters bound by both RBf1 and RBf2 require
      dE2F2/dDP. The presence of unique RBf2 targets suggest that evolutionary
      appearance of this corepressor represents the acquisition of potentially novel
      roles in gene regulation for the RB family. 

PMID- 25999586
TI  - A qualitative study of the role of workplace and interpersonal trust in shaping
      service quality and responsiveness in Zambian primary health centres.
AB  - BACKGROUND: Human decisions, actions and relationships that invoke trust are at
      the core of functional and productive health systems. Although widely studied in
      high-income settings, comparatively few studies have explored the influence of
      trust on health system performance in low- and middle-income countries. This
      study examines how workplace and inter-personal trust impact service quality and
      responsiveness in primary health services in Zambia. METHODS: This multi-case
      study included four health centres selected for urban, peri-urban and rural
      characteristics. Case data included provider interviews (60); patient interviews
      (180); direct observation of facility operations (two weeks/centre) and key
      informant interviews (14) that were recorded and transcribed verbatim. Case-based
      thematic analysis incorporated inductive and deductive coding. RESULTS: Findings
      demonstrated that providers had weak workplace trust influenced by a combination
      of poor working conditions, perceptions of low pay and experiences of inequitable
      or inefficient health centre management. Weak trust in health centre managers'
      organizational capacity and fairness contributed to resentment amongst many
      providers and promoted a culture of blame-shifting and one-upmanship that
      undermined teamwork and enabled disrespectful treatment of patients. Although
      patients expressed a high degree of trust in health workers' clinical capacity,
      repeated experiences of disrespectful or unresponsive care undermined patients'
      trust in health workers' service values and professionalism. Lack of patient
      provider trust prompted some patients to circumvent clinic systems in an attempt
      to secure better or more timely care. CONCLUSION: Lack of resourcing and poor
      leadership were key factors leading to providers' weak workplace trust and
      contributed to often-poor quality services, driving a perverse cycle of negative
      patient-provider relations across the four sites. Findings highlight the
      importance of investing in both structural factors and organizational management
      to strengthen providers' trust in their employer(s) and colleagues, as an entry
      point for developing both the capacity and a work culture oriented towards
      respectful and patient-centred care.

PMID- 25999585
TI  - The Drosophila Prosecretory Transcription Factor dimmed Is Dynamically Regulated
      in Adult Enteroendocrine Cells and Protects Against Gram-Negative Infection.
AB  - The endocrine system employs peptide hormone signals to translate environmental
      changes into physiological responses. The diffuse endocrine system embedded in
      the gastrointestinal barrier epithelium is one of the largest and most diverse
      endocrine tissues. Furthermore, it is the only endocrine tissue in direct
      physical contact with the microbial environment of the gut lumen. However, it
      remains unclear how this sensory epithelium responds to specific pathogenic
      challenges in a dynamic and regulated manner. We demonstrate that the
      enteroendocrine cells of the adult Drosophila melanogaster midgut display a
      transient, sensitive, and systemic induction of the prosecretory factor dimmed
      (dimm) in response to the Gram-negative pathogen Pseudomonas entomophila (Pe). In
      enteroendocrine cells, dimm controls the levels of the targets Phm, dcat-4, and
      the peptide hormone, Allatostatin A. Finally, we identify dimm as a host factor
      that protects against Pe infection and controls the expression of antimicrobial
      peptides. We propose that dimm provides "gain" in enteroendocrine output during
      the adaptive response to episodic pathogen exposure. 

PMID- 25999587
TI  - Evolution and prognostic impact of low flow after transcatheter aortic valve
      replacement.
AB  - OBJECTIVE: Low flow (LF), defined as stroke volume index (SVi) <35 mL/m(2), prior
      to the procedure has been recently identified as a powerful independent predictor
      of early and late mortality in patients undergoing transcatheter aortic valve
      replacement (TAVR). The objectives of this study were to determine the evolution
      of SVi following TAVR and to assess the determinants and impact on mortality of
      early postprocedural SVi (EP-SVi). METHODS: We retrospectively analysed the
      clinical, Doppler echocardiographic and outcome data prospectively collected in
      255 patients who underwent TAVR. Echocardiograms were performed before
      (baseline), within 5 days after procedure (early post procedure) and 6 months to
      1 year following TAVR (late post procedure). RESULTS: Patients with EP-SVi <35
      mL/m(2) (n=138; 54%) had increased mortality (HR 1.97, p=0.003) compared with
      those with EP-SVi >=35 mL/m(2) (n=117; 46%). Furthermore, patients with baseline
      SVi (B-SVi) <35 mL/m(2) and EP-SVI >=35 mL/m(2), that is, normalised flow, had
      better survival (HR 0.46, p=0.03) than those with both B-SVi and EP-SVi <35
      mL/m(2), that is, persistent LF, and similar survival compared with those with
      both B-SVi and EP-SVi >=35 mL/m(2), that is, maintained normal flow. In a
      multivariable model analysis, EP-SVi was independently associated with increased
      risk of mortality (HR 1.41 per 10 mL/m(2) decrease, p=0.03). The
      preprocedural/intraprocedural factors associated with lower EP-SVi were lower B
      SVi (standardised beta [beta] 0.36, p<0.001) atrial fibrillation (beta -0.13,
      p=0.02) and transapical approach (beta -0.22, p<0.001). CONCLUSIONS: The
      measurement of EP-SVi is useful to assess the immediate haemodynamic benefit of
      TAVR and to predict the risk of late mortality.

PMID- 25999588
TI  - The hypercoagulable profile of patients with stent thrombosis.
AB  - OBJECTIVE: Coronary stent thrombosis is a devastating complication after
      percutaneous coronary intervention (PCI). The mechanisms underlying stent
      thrombosis are multifactorial. Whether the coagulation system is involved in the
      pathophysiology of stent thrombosis is unclear. We hypothesised that thrombin
      generation, reflecting the coagulation potential, is enhanced in patients with
      stent thrombosis. METHODS: A case-control study was performed, including 63
      patients with PCI: 23 cases (stent thrombosis) and 40 controls (no stent
      thrombosis). Thrombin generation was measured using 0, 1 and 5 pM tissue factor
      (TF) triggers. Active site-inhibited factor VIIa (ASIS) and recombinant
      thrombomodulin were added to study the contact activation system and the protein
      C pathway, respectively. RESULTS: Thrombin generation was significantly increased
      for all TF triggers in cases compared with controls. Addition of ASIS to the
      measurement without exogenous TF revealed significantly enhanced contact
      activation in cases compared with controls; mean peak height: 241 vs 183 nM.
      Thrombin generation was also significantly increased in cases compared with
      controls in the presence of exogenous TF; mean peak height: 263 vs 233 nM (5 pM
      TF). Addition of thrombomodulin reduced thrombin generation by 23% in cases and
      31% in controls (p<0.018), suggesting alterations in the protein C pathway in
      cases. CONCLUSIONS: This is the first study that suggests the involvement of the
      coagulation system in stent thrombosis. Stent thrombosis patients showed a
      hypercoagulable state, most likely caused by enhanced contact activation and
      attenuation of anticoagulation by the protein C pathway.

PMID- 25999590
TI  - Pseudomonas coleopterorum sp. nov., a cellulase-producing bacterium isolated from
      the bark beetle Hylesinus fraxini.
AB  - We isolated a strain coded Esc2Am(T) during a study focused on the microbial
      diversity of adult specimens of the bark beetle Hylesinus fraxini. Its 16S rRNA
      gene sequence had 99.4% similarity with respect to its closest relative,
      Pseudomonas rhizosphaerae IH5(T). The analysis of partial sequences of the
      housekeeping genes rpoB, rpoD and gyrB confirmed that strain Esc2Am(T) formed a
      cluster with P. rhizosphaerae IH5(T) clearly separated from the remaining species
      of the genus Pseudomonas. Strain Esc2Am(T) had polar flagella and could grow at
      temperatures from 4  degrees C to 30  degrees C. The respiratory quinone was Q9
      and the main fatty acids were C16 : 0, C18 : 1omega7c and/or C18 : 1omega6c in
      summed feature 8 and C16 : 1omega7c and/or C16 : 1omega6c in summed feature 3.
      DNA-DNA hybridization results showed 51% relatedness with respect to P.
      rhizosphaerae IH5(T). Oxidase, catalase and urease-positive, the arginine
      dihydrolase system was present but nitrate reduction and beta-galactosidase
      production were negative. Aesculin hydrolysis was positive. Based on the results
      from the genotypic, phenotypic and chemotaxonomic analyses, we propose the
      classification of strain Esc2Am(T) as representing a novel species of the genus
      Pseudomonas, for which we propose the name Pseudomonas coleopterorum sp. nov. The
      type strain is Esc2Am(T) ( = LMG 28558(T)= CECT 8695(T)).

PMID- 25999589
TI  - Functional Dissociation of Group III Metabotropic Glutamate Receptors Revealed by
      Direct Comparison between the Behavioral Profiles of Knockout Mouse Lines.
AB  - BACKGROUND: Group III metabotropic glutamate receptors (mGlu4, mGlu7, mGlu8)
      display differential brain distribution, which suggests different behavioral
      functions. However, comparison across the available animal studies remains
      methodologically hazardous and controversial. The present report directly
      compares knockouts for each group III receptor subtype using a single behavioral
      test battery and multivariate analysis. METHODS: The behavioral phenotypes of
      C57BL/6J mice lacking mGlu4, mGlu7, or mGlu8 and their respective littermates
      were examined using a multimetric test battery, which included elements of
      neuromotor performance, exploratory behavior, and learning and memory.
      Multivariate statistical methods were used to identify subtype-specific
      behavioral profiles and variables that distinguished between these mouse lines.
      RESULTS: It generally appears that mGlu7 plays a significant role in hippocampus
      dependent spatial learning and in some fear-related behaviors, whereas mGlu4 is
      most clearly involved in startle and motivational processes. Excepting its
      influence on body weight, the effect of mGlu8 deletion on behavior appears more
      subtle than that of the other group III receptors. These receptors have been
      proposed as potential drug targets for a variety of psychopathological
      conditions. CONCLUSION: On the basis of these controlled comparisons, we
      presently conclude that the different group III receptors indeed have quite
      distinct behavioral functions.

PMID- 25999591
TI  - Brassicibacter thermophilus sp. nov., a thermophilic bacterium isolated from
      coastal sediment.
AB  - A novel thermophilic, obligately anaerobic bacterium, strain Cel2f(T), was
      isolated from a cellulolytic community enriched from coastal marine sediment.
      Cells were Gram-stain-negative, non-motile, non-spore-forming and rod-shaped.
      Optimal growth temperature and pH of strain Cel2f(T) were 55  degrees C and pH
      7.0, respectively. NaCl was essential for the growth of strain Cel2f(T) and the
      strain showed enhanced growth in the presence of sea salt; the optimum sea salt
      concentration for growth was 7% (w/v). Thiosulfate, sulfate and sulfite were
      potential electron acceptors. The major fatty acids of strain Cel2f(T) were iso
      C15 : 0, C16 : 0, and C18 : 0. Polar lipid analysis indicated the presence of
      phosphatidylethanolamine and phosphatidylglycerol. Strain Cel2f(T) contained
      menaquinone MK-7 as the isoprenoid quinone, and the DNA G+C content was 31.3
      mol%. Phylogenetic analysis revealed that the nearest relative of strain Cel2f(T)
      was Brassicibacter mesophilus BM(T) with 93.8% 16S rRNA gene sequence similarity.
      Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain
      Cel2f(T) represents a novel species of genus Brassicibacter, for which the name
      Brassicibacter thermophilus sp. nov. is proposed. The type strain is Cel2f(T) ( =
      JCM 30480(T) = CGMCC 1.5200(T)).

PMID- 25999592
TI  - Genome-based taxonomic framework for the class Negativicutes: division of the
      class Negativicutes into the orders Selenomonadales emend., Acidaminococcales
      ord. nov. and Veillonellales ord. nov.
AB  - The class Negativicutes is currently divided into one order and two families on
      the basis of 16S rRNA gene sequence phylogenies. We report here comprehensive
      comparative genomic analyses of the sequenced members of the class Negativicutes
      to demarcate its different evolutionary groups in molecular terms, independently
      of phylogenetic trees. Our comparative genomic analyses have identified 14
      conserved signature indels (CSIs) and 48 conserved signature proteins (CSPs) that
      either are specific for the entire class or differentiate four main groups within
      the class. Two CSIs and nine CSPs are shared uniquely by all or most members of
      the class Negativicutes, distinguishing this class from all other sequenced
      members of the phylum Firmicutes. Four other CSIs and six CSPs were specific
      characteristics of the family Acidaminococcaceae, two CSIs and four CSPs were
      uniquely present in the family Veillonellaceae, six CSIs and eight CSPs were
      found only in Selenomonas and related genera, and 17 CSPs were identified
      uniquely in Sporomusa and related genera. Four additional CSPs support a pairing
      of the groups containing the genera Selenomonas and Sporomusa. We also report
      detailed phylogenetic analyses for the Negativicutes based on core protein
      sequences and 16S rRNA gene sequences, which strongly support the four main
      groups identified by CSIs and by CSPs. Based on the results from different lines
      of investigation, we propose a division of the class Negativicutes into an
      emended order Selenomonadales containing the new families Selenomonadaceae fam.
      nov. and Sporomusaceae fam. nov. and two new orders, Acidaminococcales ord. nov.
      and Veillonellales ord. nov., respectively containing the families
      Acidaminococcaceae and Veillonellaceae. 

PMID- 25999593
TI  - Pichia dushanensis sp. nov. and Hyphopichia paragotoi sp. nov., two sexual yeast
      species associated with insects and rotten wood.
AB  - Seven yeast strains were isolated from the gut of insect larvae and decayed wood,
      which were collected from three localities near Nanyang, Henan Province, China.
      These strains were identified as two novel species through comparison of
      sequences in the D1/D2 domains of the large subunit (LSU) rRNA gene and other
      taxonomic characteristics. Pichia dushanensis sp. nov. was closely related to
      species in the Pichia clade and produced one to four spheroid ascospores in a
      deliquescent ascus. The D1/D2 sequence of P. dushanensis sp. nov. differed from
      its closest relative, Issatchenkia (Pichia) sp. NRRL Y-12824, by 3.6% sequence
      divergence (16 substitutions and 4 gaps). The species also differed from its four
      closest known species, Candida rugopelliculosa, Pichia occidentalis, Pichia
      exigua and Candida phayaonensis, by 4.1-4.4% sequence divergence (22-24
      substitutions and 0-2 gaps) in the D1/D2 sequences. Hyphopichia paragotoi sp.
      nov. belonged to the Hyphopichia clade, and its nearest phylogenetic neighbours
      were Candida gotoi, Candida pseudorhagii, Candida rhagii and Hyphopichia heimii
      with 3.2-4.2% sequence divergence (16-21 substitutions and 1 gap) in the D1/D2
      sequences. In comparison with previously established species, H. paragotoi sp.
      nov. formed one hat-shaped ascospore in a persistent ascus. The type strain of P.
      dushanensis sp. nov. is NYNU 14658(T) ( = CICC 33049(T) = CBS 13912(T)), and the
      type strain of H. paragotoi sp. nov. is NYNU 14666(T) ( = CICC 33048(T) = CBS
      13913(T)).

PMID- 25999594
TI  - Shewanella electrodiphila sp. nov., a psychrotolerant bacterium isolated from Mid
      Atlantic Ridge deep-sea sediments.
AB  - Strains MAR441(T) and MAR445 were isolated from Mid-Atlantic Ridge sediments from
      a depth of 2734 m, and were found to belong to 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,
      which used carbon cloth electrodes and delivered a stable power output of ,150
      200 mW m(-2). The major fatty acids were typical of the genus Shewanella, with
      major components 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
      MAR441(T) and MAR445 was 42.4 mol%. 16S rRNA gene sequence analysis indicated
      that strains MAR441(T) and MAR445 were most closely related to Shewanella
      olleyana (sequence similarities 97.9% to the type strain). DNA-DNA hybridization
      demonstrated only 15.6-37.2% relatedness between strain MAR441(T) and the type
      strains of related species of the genus Shewanella. Phenotypic characteristics
      confirmed that these isolates constituted a novel species of the genus
      Shewanella, for which the name Shewanella electrodiphila sp. nov. is proposed;
      the type strain is MAR441(T) (5ATCC BAA-2408(T) = DSM 24955(T)).

PMID- 25999595
TI  - Winogradskyella crassostreae sp. nov., isolated from an oyster (Crassostrea
      gigas).
AB  - A Gram-stain-negative, non-flagellated, non-gliding, aerobic and rod-shaped
      bacterium, designated TYO-19(T), was isolated from an oyster collected from the
      South Sea in South Korea, and was subjected to a taxonomic study using a
      polyphasic approach. Strain TYO-19(T) grew optimally at 30  degrees C, at pH 7.0
      8.0 and in the presence of 1.0-2.0% (w/v) NaCl. Phylogenetic trees based on 16S
      rRNA gene sequences showed that strain TYO-19(T) belonged to the genus
      Winogradskyella, clustering coherently with the type strain of Winogradskyella
      epiphytica. Strain TYO-19(T) exhibited a 16S rRNA gene sequence similarity value
      of 99.7% to W. epiphytica KMM 3906(T) and 94.2-96.9% to the type strains of other
      species of the genus Winogradskyella. Strain TYO-19(T) contained MK-6 as the
      predominant menaquinone and iso-C15 : 1 G, iso-C17 : 0 3-OH, iso-C15 : 0 and
      anteiso-C15 : 0 as the major fatty acids. The major polar lipids detected in
      strain TYO-19(T) were phosphatidylethanolamine and one unidentified lipid. The
      DNA G+C content was 39.0 mol% and the mean DNA-DNA relatedness value with the
      type strain of W. epiphytica was 59 +/- 4.3%. Differential phenotypic properties,
      together with phylogenetic and genetic distinctiveness, revealed that strain TYO
      19(T) is separated from recognized species of the genus Winogradskyella. On the
      basis of the data presented, strain TYO-19(T) is considered to represent a novel
      species of the genus Winogradskyella, for which the name Winogradskyella
      crassostreae sp. nov. is proposed. The type strain is TYO-19(T) ( = KCTC 42462(T)
      = NBRC 110924(T)).

PMID- 25999596
TI  - IL-10-independent regulatory B-cell subsets and mechanisms of action.
AB  - Although classically B cells are known to play important roles in immune
      protection via humoral immunity, recently their regulatory mechanisms have been
      best appreciated in the context of autoimmunity. Several studies have identified
      different subsets of regulatory B cells that vary not only in their phenotype but
      also in their mechanism of action. Although the best-studied mechanism of B-cell
      immune regulation is IL-10 production, other IL-10-independent mechanisms have
      been proposed. These include maintenance of CD4(+)Foxp3(+) regulatory T cells;
      production of transforming growth factor-beta, IL-35, IgM or adenosine or
      expression of PD-L1 (programmed death 1 ligand 1) or FasL (Fas ligand). Given
      that B-cell-targeted therapy is being increasingly used in the clinic, a complete
      understanding of the mechanisms whereby B cells regulate inflammation associated
      with specific diseases is required for designing safe and effective
      immunotherapies targeting B cells. 

PMID- 25999598
TI  - The Effects of the Crisis: Why Southern Europe?

PMID- 25999597
TI  - Regulatory B cells in anti-tumor immunity.
AB  - Advances in understanding of the immune microenvironment have highlighted the
      role of immunosuppressive T cell, myeloid, dendritic and monocytic sub
      populations in inhibition of the anti-tumor immune response. The role of B cells
      in modulating the immune response to solid tumors as well as lymphoid
      malignancies is less well understood. Murine models of autoimmune disease have
      defined B regulatory cell (Breg) subsets with immune suppressive activity,
      including B cell subsets that express IL-10, and transforming growth factor-beta,
      which can facilitate T regulatory cell recruitment and expansion. Multiple murine
      tumor models point to the existence of similar immune suppressive B cell sub
      populations that can migrate into tumor deposits and acquire an immune
      suppressive phenotype, which then leads to attenuation of the local anti-tumor
      immune response. Other murine models of viral or chemically induced skin
      carcinogenesis have identified a pivotal role for B cells in promoting
      inflammation and carcinogenesis. While many human solid tumors demonstrate
      significant B cell infiltration and/or tertiary lymphoid structure formation, the
      functional properties of tumor-infiltrating B cells and their effects on immunity
      are poorly understood. Recent successes in early Phase I/II trials using anti
      checkpoint inhibitor antibodies such as nivolumab or pidilizumab directed against
      PD-1 in the setting of Hodgkin's and non-Hodgkin's lymphomas validate the
      therapeutic utility of reversing B cell-mediated immune suppression. Further
      studies to define Breg subsets, and mechanisms of suppression, may provide new
      avenues for modulation of the immune response and meaningful therapeutic
      intervention in both lymphoid and solid tumors. 

PMID- 25999600
TI  - Ethnic Identification and its Consequences for Measuring Inequality in Mexico.
AB  - This paper examines ethnic boundary crossing and its impact on estimates of
      ethnic disparities in children's outcomes in the specific context of Mexico, a
      country with the largest indigenous population in the Western hemisphere. The
      boundary that separates the indigenous and non-indigenous population is known to
      be extremely fluid as it is based on characteristics that can easily change
      within a generation such as language use, cultural practices and a subjective
      sense of belonging. Using data from the Mexican census I examine the ethnic
      classification of children of indigenous parents. I find that movement across the
      ethnic boundary depends on which of the two criteria currently recognized by the
      Mexican census is used. Children of indigenous parents are much less likely to be
      classified as indigenous according to language proficiency, especially when their
      parents have higher levels of education. By contrast, when proxy self
      identification is used as a criterion, children of indigenous parents are more
      likely to be classified as indigenous, and greater parental education actually
      results in higher odds that children will be classified as indigenous. The shift
      in children's indigenous classification with parental education is found to
      strongly affect estimates of educational disparities between indigenous and non
      indigenous children.

PMID- 25999599
TI  - The War on Poverty's Experiment in Public Medicine: Community Health Centers and
      the Mortality of Older Americans.
AB  - This paper uses the rollout of the first Community Health Centers (CHCs) to study
      the longer-term health effects of increasing access to primary care. Within ten
      years, CHCs are associated with a reduction in age-adjusted mortality rates of 2
      percent among those 50 and older. The implied 7 to 13 percent decrease in one
      year mortality risk among beneficiaries amounts to 20 to 40 percent of the 1966
      poor/non-poor mortality gap for this age group. Large effects for those 65 and
      older suggest that increased access to primary care has longer-term benefits,
      even for populations with near universal health insurance. (JEL H75, I12, I13,
      I18, I32, I38, J14).

PMID- 25999601
TI  - Prenatal exposure to violence and birth weight in Mexico: Selectivity, exposure,
      and behavioral responses.

PMID- 25999603
TI  - Placing Families in Context: Challenges for Cross-National Family Research.
AB  - Cross-national comparisons constitute a valuable strategy to assess how broader
      cultural, political, and institutional contexts shape family outcomes. One
      typical approach of cross-national family research is to use comparable data from
      a limited number of countries, fit similar regression models for each country,
      and compare results across country-specific models. Increasingly, researchers are
      adopting a second approach, which requires merging data from many more societies
      and testing multilevel models using the pooled sample. Although the second
      approach has the advantage of allowing direct estimates of the effects of nation
      level characteristics, it is more likely to suffer from the problems of omitted
      variable bias, influential cases, and measurement and construct nonequivalence. I
      discuss ways to improve the first approach's ability to infer macrolevel
      influences, as well as how to deal with challenges associated with the second
      one. I also suggest choosing analytical strategies according to whether the data
      meet multilevel models' assumptions.

PMID- 25999602
TI  - Leisure-time physical activity moderates the longitudinal associations between
      work-family spillover and physical health.
AB  - Previous research has documented cross-sectional associations between negative
      and positive work-family spillover and physical health. Using an effort-recovery
      model, the study tested the hypothesis that engagement in greater leisure-time
      physical activity would facilitate recovery processes that buffer the negative
      health effects of increasing work-family spillover. Employed adults (N = 1,354)
      completed two waves of the National Survey of Midlife Development in the United
      States (MIDUS). Results indicated that an increase in negative work-family
      spillover across nine years was associated with decreased physical health and
      increased number of chronic conditions at Time 2. Moreover, more time spent on
      moderate leisure-time physical activity buffered many of the associations between
      increasing negative spillover and declining health. Implications of the findings
      are discussed.

PMID- 25999604
TI  - Bad medicine: "Contraception for adolescents".

PMID- 25999605
TI  - Declaration of faith of Catholic doctors and students of medicine, on the
      sexuality and fertility of human beings.

PMID- 25999606
TI  - Gay inspiration in the interim report of the bishops' synod.

PMID- 25999607
TI  - Lazarus, come out!

PMID- 25999608
TI  - Embracing the spiritual history.

PMID- 25999609
TI  - The reunion of the Good Shepherd with the Good Samaritan.

PMID- 25999610
TI  - Healing and hope in the midst of suffering and death.

PMID- 25999611
TI  - Pain medicine and palliative care as an alternative to euthanasia in end-of-life
      cancer care.
AB  - There exists support for euthanasia or physician-assisted suicide (PAS) in cases
      of terminal cancer. One of the premises for this approach is the goal of the
      alleviation of suffering. Do current means of pain control in the greater overall
      setting of palliative care serve as a desirable alternative? A contrast
      comparison may be drawn between the above approaches using both theological and
      medical sources to show that the enlightened use of both interventional and non
      interventional pain medicine approaches in an integrated palliative care setting
      are a theologically grounded and medically feasible alternative to euthanasia or
      PAS in this population. Lay summary: Patients suffering from terminal cancer
      often have pain. Some have advocated euthanasia or physician-assisted suicide as
      a potential way of alleviating this suffering. Further examination of this topic,
      however, shows this approach may be essentially utilitarian and fail to consider
      the inherent value of human life. There has been significant development in
      recent years in the fields of pain medicine and palliative care, which afford
      alternate means of addressing suffering in this patient population. 

PMID- 25999612
TI  - Contraception and abortion: Fruits of the same rotten tree?
AB  - This article seeks to show how contraception, when generally accepted in a
      society, helps to bring about a radical change in social perceptions of sexual
      intercourse, human life, the human person, science, and morality in general. On
      account of this, contraception helps to ingrain abortion and other anti-life
      practices into the culture that accepts it and, therefore, in no sense can be
      considered as a panacea for abortion. Particular attention is given to the
      thought of John Paul II on this matter who noted that "despite their differences
      of nature and moral gravity, contraception and abortion are often closely
      connected, as fruits of the same tree" (Evangelium vitae, n. 13). Lay summary:
      The article considers the connection between contraception and abortion and
      defends Pope John Paul II's claim that "despite their differences of nature and
      moral gravity, contraception and abortion are often closely connected, as fruits
      of the same tree." The thesis is that contraception is a "game-changer" in the
      sense that it changes the way we think about some very fundamental realities such
      as attitudes to sex, to life, to science, to the human person, and to morality.
      Any one of these changes would have a significant impact on a society in terms of
      promoting a culture of death: together they are devastating. 

PMID- 25999613
TI  - Integrity and virtue: The forming of good character.
AB  - Moral character is formed by one's actions. The habits, actions, and emotional
      responses of the person of good character all are united and directed toward the
      moral and the good. Because human beings are body/soul unities, actions of the
      body are actions of the self, that is, human beings are self-possessing, self
      governing, and self-determining. In order to be of good character, one must know
      the good, act in morally good ways, and be disposed and inclined toward the good
      through the development of virtues. Character and action are intertwined so
      intimately that one's professional duties, or even what is perceived by others as
      one's duties, cannot override one's conscience without negatively affecting (and
      changing) one's character. For the physician to be of good character, it is vital
      that he or she follow his or her conscience in all things: in private life and
      also in his or her profession, i.e., in the treatment of patients. Lay summary:
      Character cannot be separated from the person. To be of good character means that
      one's habits, actions, and emotional responses all are united and directed toward
      the moral and the good. In this, public actions cannot be separated from private
      actions. Both sets of actions affect one's character. For example, a physician
      believes use of contraceptives to be immoral yet prescribes them in the office
      because he or she feels a duty to provide what the patient asks for, or a
      pharmacist who believes abortion to be immoral fills prescriptions for the
      abortifacient RU-486. These public acts affect one's character even if one's
      private belief is the opposite of the action. They leave traces on one's
      character. Not only do actions reflect the goodness or badness of one's
      character, one's actions also change one's character. The more one does an
      immoral action or recommends an immoral action for others, the more it becomes
      part of one's character to be the type of person who condones that immoral
      action. In order to be of good character one must not only know and desire the
      good, one must also pursue it in both private and public actions. Virtue is an
      aid in this; it is the act of good character. Growing in the virtues, especially
      prudence (knowing what to seek and what to avoid) forms good character. What is
      at stake is the integrity of the person. The physician who believes that use of
      contraception is immoral must also act in ways that display that belief and avoid
      actions that promote contraception use by his or her patients. 

PMID- 25999614
TI  - Pastoral care of patients with Ebola Virus Disease: A medical and canonical
      opinion about pastoral visits to patients with contagious and highly fatal
      diseases.
AB  - The Ebola Virus Disease is a contagious and highly fatal illness that up until
      recently had been geographically limited to remote areas of Africa. In 2014,
      Ebola patients have been transported to the United States for care or have been
      newly diagnosed in the United States. With the intensive medical care and
      isolation policies usually needed by these patients, we inquired whether pastoral
      care would be possible. Using clinical and canonical considerations, we analyzed
      the permissibility and logistical challenges pastoral care presents to the
      priests and lay ministers, as well as the healthcare system. We conclude that
      with the approval of local, state, and federal health officials, pastoral care,
      including provision of the sacraments, is possible. It would require proper
      training, proper equipment and policies, and a significant commitment of time.
      While the risk to the pastoral team is difficult to define, it seems low in an
      Ebola-capable medical system. These risks to priests and ministers seem
      reasonable given the inestimable benefits of receiving the sacraments during
      critical illness. Lay summary: Traditional pastoral visits to hospitalized
      patients might prove difficult or impossible for diseases that are contagious and
      highly fatal. This inquiry examines the feasibility, challenges, and logistical
      solutions to these visits. With input from bishops, priests, a canon lawyer, an
      epidemiologist, a physician, the CDC, and others, we conclude that pastoral
      visits are possible. Visits will require permission of health authorities,
      commitments of time, training, and a small but significant risk to the health of
      priests and others who volunteer for this ministry. 

PMID- 25999615
TI  - Determination of the Polymer-Solvent Interaction Parameter for PEG Hydrogels in
      Water: Application of a Self Learning Algorithm.
AB  - Concentrating on the case of poly(ethylene glycol) hydrogels, this paper
      introduces a methodology that enables a natural integration between the
      development of a so-called mechanistic model and experimental data relating
      material's processing to response. In a nutshell, we develop a data-driven
      modeling component that is able to learn and indirectly infer its own parameters
      and structure by observing experimental data. Using this method, we investigate
      the relationship between processing conditions, microstructure and chemistry
      (cross-link density and polymer-solvent interactions) and response (swelling and
      elasticity) of non-degradable and degradable PEG hydrogels. We show that the
      method not only enables the determination of the polymer-solvent interaction
      parameter, but also it predicts that this parameter, among others, varies with
      processing conditions and degradation. The proposed methodology therefore offers
      a new approach that accounts for subtle changes in the hydrogel processing.

PMID- 25999616
TI  - PRACTICAL SYNTHESIS OF AROMATIC DITHIOCARBAMATES.
AB  - Oxidation-sensitive N,N-diaryl dithiocarbamates (DTCs) are synthesized in good
      yields by the generation of metal amide salts from N-benzoyl precursors, followed
      by addition of CS2. para-Substituted diphenylamines are prepared by electrophilic
      aromatic substitution of diphenylbenzamide and saponification. Deacylation of
      electron-rich species such as bis(p-dimethylaminophenyl)benzamide is challenging
      because of the oxidative sensitivity of the anionic intermediate but could be
      achieved in good yield by using n-BuLi to generate a hemiaminal adduct, prior to
      acidification. The N,N-diaryl DTCs are stable as alkali salts and can be used to
      produce densely packed monolayers on gold surfaces.

PMID- 25999617
TI  - The impact of low- and moderate-wealth homeownership on parental attitudes and
      behavior: Evidence from the community advantage panel.
AB  - Considerable research has suggested that homeownership imparts a variety of
      positive individual, family, neighborhood, and community effects. Yet, much of
      the research to date has failed to examine such effects by level of income
      [Dietz, R.D., & Haurin, D.R. (2003). The social and private micro-level
      consequences of homeownership. Journal of Urban Economics, 54(3), 401-450.]. This
      study adds to the limited research on the impact of assets on parental attitude
      and behavior among low- and moderate-income (LMI) families. Data used in this
      study are from the evaluation of Self-Help's Community Advantage Home Loan
      Secondary Market Program. Specifically, we focus on the differences in the
      demographic and financial backgrounds, and parental attitudes and behavior
      between LMI homeowners and a comparison group of renters (n=815 owners; n=333
      renters). Logistic regression analyses are used to model parental attitude and
      behavior outcomes on tenure, controlling for a variety of household
      characteristics. Results show that the overall differences between homeowners and
      renters on parental outcomes are statistically nonsignificant. This finding
      implies that tenure per se is not associated with parental attitudes and
      behavior. Explanations for the possible reasons for the lack of a tenure effect
      are discussed. Policy implications are forwarded.

PMID- 25999619
TI  - Sexual dysfunction in women with type 2 diabetes mellitus.
AB  - BACKGROUND: Sexual dysfunction (SD) is one of the important problems in diabetic
      patients. The present study aimed to determine the prevalence of sexual problems
      in Iranian women with type 2 diabetes mellitus. METHODS: A cross-sectional study
      was conducted among type 2 diabetic women who visited two outpatient endocrine
      clinics, namely Imam Hospital and Tuba clinic (Sari, Iran) in 2012. Patients were
      asked to complete two validated questionnaires: Female Sexual Function Index
      (FSFI) and The Hospital Anxiety and Depression Scale (HADS) as well as a
      demographic questionnaire. Analysis was performed using descriptive and
      analytical tests. P<0.05 was considered to be significant. RESULTS: One hundred
      and fifty women with type 2 diabetes were investigated. Most of the cases aged 40
      44 years old. The mean of the total score of the FSFI questionnaire was 22. The
      prevalence of sexual dysfunction was 78.7% (CI: 71.4-84.4); among these, 58% (CI:
      50.0-65.6) reported problems in lubrication, 50% (CI: 42.1-57.9) complained of
      decreased sexual desire, 50% (CI: 42.1-57.9) had problems with arousal, 47.3%
      (CI: 39.5-55.3) had dyspareunia, 32.7% (CI: 25.7-40.5) complained of orgasmic
      dysfunction and 42.7% (CI: 35.0-50.7) reported problems in sexual satisfaction.
      With regard to the results of the HADS questionnaire, 58.7% (CI: 50.7-66.2) of
      the patients had depression and 96.7% (CI: 92.4-98.6) had anxiety. CONCLUSION:
      This study showed the high prevalence of sexual dysfunction in diabetic women,
      especially among those complaining of depression. Health care professionals
      dealing with diabetic patients should be aware of possible presence of sexual
      dysfunction in female patients.

PMID- 25999618
TI  - Clinical and laboratory approaches to hemophilia a.
AB  - Hemophilia A is a worldwide disorder of coagulation system. It is a male
      disorder, yet females with hemophilia are rarely seen in communities with high
      rate of consanguineous marriages. The abnormalities in factor VIII gene transfer
      as an X-linked pattern in the family, affects as many as one-third of patients
      who had no family history of abnormality and thus the occurrence of a sporadic
      mutation could be documented. Hemorrhagic symptoms usually correlate with the
      plasma level of factor VIII and comprise a wide range of hemorrhagic pictures,
      including from fatal spontaneous bleeding in the brain to ecchymosis of the skin.
      The coagulation study needs to differentiate between the two types of hemophilia
      A and B as well as the categorization of the disease severity. In the developing
      countries, due to limitations in diagnostic hemostasis facilities and a scant
      number of experts in the field, it is estimated that noticeable numbers of
      undiagnosed patients with hemophilia A exist. Occasionally, we encounter
      undiagnosed cases by general physicians while having hemorrhagic symptoms. The
      purpose of this review is to recap clinical and diagnostic parameters, pitfalls,
      and interpretation of coagulation assay in hemophilia A. A literature review was
      done in PubMed and Scopus medical search engines using the keywords "Hemophilia"
      and "Haemophilia". A time limitation for the publication beyond 1995 and
      publication in the English language were considered. A total of 94 original
      articles and chapters of books was selected for the current review. Additionally,
      a comprehensive and up-to-date information on the clinical and laboratory
      features for the diagnosis of hemophilia is also presented. 

PMID- 25999620
TI  - Serum selenium level in patients with gastric non-cardia cancer and functional
      dyspepsia.
AB  - BACKGROUND: Gastric cancer (GC) is the most common gastrointestinal cancer in
      Iran. Helicobacter pylori (H. pylori) accounts as one of the main risk factors
      for gastric non-cardia cancer (GNCC). It is suggested that high serum selenium
      level may have a protective role in GNCC. In this cross-sectional study, we
      determined the serum Se level and the status of H. pylori infection in two
      populations with GC and functional dyspepsia (FD). METHODS: The enrolled patients
      were 85 (27 women, 58 men) with recent pathologically proven GNCC
      (adenocarcinoma) and 85 (34 women, 51 men) FD patients. Serum Se was measured by
      atomic absorption spectrophotometry. H. pylori IgG antibody was detected by
      quantitative enzyme immunoassay. RESULTS: The mean age in the GNCC and FD
      patients were 62.85+/-14.6 and 58.9+/-14.7 years, respectively (P=0.08). The
      serum selenium levels were 111.6+/-27.7 and 129.9+/-32.1 MUg/L (mean+/-SD) in
      GNCC and FD patients, respectively (P<0.001). The frequency of H. pylori
      infection was 49.4% (n=42) and 68.2% (n=58) in GNCC and FD patients (P=0.013).
      The crude and adjusted odds ratio (OR) between GNCC and the linear effect of
      serum selenium level were 0.98 and 0.982, respectively (P=0.002). This means that
      each unit increase in serum selenium level decreases the odds of cancer by 2%.
      CONCLUSION: Serum selenium level was significantly lower in GNCC cases. It
      suggests that lower serum selenium might have some association with the risk of
      GNCC. H. pylori infection does not play a significant impact on this association.

PMID- 25999621
TI  - The Effect of Virtual Reality on Pain in Primiparity Women during Episiotomy
      Repair: A Randomize Clinical Trial.
AB  - BACKGROUND: Pain is one of the side effects of episiotomy. The virtual reality
      (VR) is a non-pharmacological method for pain relief. The purpose of this study
      was to determine the effect of using video glasses on pain reduction in
      primiparity women during episiotomy repair. METHODS: This clinical trial was
      conducted on 30 primiparous parturient women having labor at Omolbanin Hospital
      (Mashhad, Iran) during May-July 2012. Samples during episiotomy repair were
      randomly divided into two equal groups. The intervention group received the usual
      treatment with VR (video glasses and local infiltration 5 ml solution of
      lidocaine 2%) and the control group only received local infiltration (5 ml
      solution of lidocaine 2%). Pain was measured using the Numeric Pain Rating Scale
      (0-100 scale) before, during and after the episiotomy repair. Data were analyzed
      using Fisher's exact test, Chi-square, Mann-Whitney and repeated measures ANOVA
      tests by SPSS 11.5 software. RESULTS: There were statistically significant
      differences between the pain score during episiotomy repair in both groups
      (P=0.038). CONCLUSION: Virtual reality is an effective complementary non
      pharmacological method to reduce pain during episiotomy repair. TRIAL
      REGISTRATION NUMBER: IRCT138811063185N1.

PMID- 25999622
TI  - Cytokines, chemokines, and chemokine receptors quantitative expressions in
      patients with ovarian cancer.
AB  - BACKGROUND: Cytokines, chemokines, and chemokine receptors regulate the
      proliferation and survival of tumor cells, angiogenesis, and metastasis to other
      organs. This network of ligands and receptors has been used in molecular
      targeting of cancer. METHODS: We compared the mRNA expression of CXCR3, CXCL-10,
      CXCR4, CXCL-12, IL-4, and IL-10 in tissues of benign and malignant ovarian tumors
      by qRT-PCR method and evaluated serum IL-10 and CA-125 content of these patients
      by ELISA during one year. RESULTS: Our result showed a trend toward a higher
      expression of CXCR4 in malignant ovarian tissues compared with the benign ovarian
      cysts (P>0.05). However, SDF-1, IP-10, IL-4, CXCR3, and IL-10 had a lower trend
      in mRNA expression in malignant ovarian tissues compared to the benign cyst
      tissues. Except for IL-4 (P=0.01) and SDF-1 (P=0.02), the data for other factors
      were not statistically significant. A trend toward higher concentration of IL-10
      was observed in the serum of ovarian cancer patients compared to those with
      benign cysts; however, the difference was not significant. CA-125 concentration
      in the serum of ovarian cancer patients was higher than that of benign cyst
      patients (P=0.05). CONCLUSION: According to results obtained, we hypothesize that
      the lower expression of SDF-1 in malignant tissues may have an important role in
      ovarian tumor growth. However, this hypothesis requires more investigation.
      Higher levels of CA125 and IL-10 in the serum of patients might indicate that the
      combination of these biomarkers could be used for distinguishing patients with
      ovarian cancer from those with benign cysts.

PMID- 25999623
TI  - Survival analysis and its associated factors of Beta thalassemia major in hamadan
      province.
AB  - BACKGROUND: There currently is a lack of knowledge about the long-term survival
      of patients with beta thalassemia (BT), particularly in regions with low
      incidence of the disease. The aim of the present study was to determine the
      survival rate of the patients with BT major and the factors associated with the
      survival time. METHODS: This retrospective cohort study was performed in Hamadan
      province, located in the west of Iran. The study included patients that referred
      to the provincial hospitals during 16 year period from 1997 to 2013. The follow
      up of each subject was calculated from the date of birth to the date of death.
      Demographic and clinical data were extracted from patients' medical records using
      a checklist. Statistical analysis included the Kaplan-Meier method to analyze
      survivals, log-rank to compare curves between groups, and Cox regression for
      multivariate prognostic analysis. RESULTS: A total of 133 patients with BT major
      were enrolled, 54.9% of whom were male and 66.2% were urban. The 10-, 20- and 30
      year survival rate for all patients were 98.3%, 88.4% and 80.5%, respectively.
      Based on hazard ratio (HR), we found that accompanied diseases (P=0.01), blood
      type (P=0.03) and residency status (P=0.01) were significant predictors for the
      survival time of patients. CONCLUSION: The survival rate of BT patients has
      improved. Future researches such as prospective designs are required for the
      estimation of survival rate and to find other prognostic factors, which have
      reliable sources of data.

PMID- 25999624
TI  - Attenuation of morphine physical dependence and blood levels of cortisol by
      central and systemic administration of ramelteon in rat.
AB  - BACKGROUND: Chronic administration of morphine cause physical dependence but the
      exact mechanism of this phenomenon remains unclear. The aim of this study is the
      assessment of systemic and intracerebroventricular (icv) administration of
      ramelteon (a melatonin receptor agonist) on morphine physical dependence.
      METHODS: 88 adult male rats were divided into 2 major groups, namely "systematic"
      and "central" administration of ramelteon. In the first category, systemic
      administration of ramelteon at various dosages (10, 20, and 40 mg/kg) was
      assessed on dependent animals and withdrawal signs were compared with positive
      (received morphine and saline as systemic administration), negative control
      (saline) and group under treatment by ramelteon (40 mg/kg) groups. In the second
      category, central administration of ramelteon at various dosages (25, 50, or 100
      MUg,) was assessed on dependent animals and withdrawal signs were compared with
      the positive control (received morphine and saline as icv) and negative control
      (saline) groups, and the group under treatment by ramelteon (50 MUg/5 MUl/rat).
      On the test day, all animals received naloxone (3 mg/kg) and were observed for
      withdrawal signs. Total withdrawal score (TWS) was also determined. Finally, to
      evaluate the stress level of dependent rats, blood cortisols were measured.
      RESULTS: Central administration of ramelteon in all doses and systemic
      administration in high doses attenuate withdrawal syndrome in comparison with the
      dependent positive control group (P<0.05). Both central and systemic
      administrations of ramelteon can attenuate the blood cortisol level in comparison
      with the dependent positive control group (P<0.05). CONCLUSION: In conclusion, we
      found that central administration of ramelteon attenuated morphine withdrawal
      symptoms and cortisol level as a stress marker.

PMID- 25999625
TI  - Effect of Resveratrol Supplementation on the SNARE Proteins Expression in Adipose
      Tissue of Stroptozotocin-Nicotinamide Induced Type 2 Diabetic Rats.
AB  - BACKGROUND: Glucose uptake by muscles and fat cells is carried out by the GLUT4
      system. Isoforms of the SNAP23, syntaxin-4 and VAMP-2 play an important role in
      regulating GLUT-4 trafficking and fusion in adipocytes. The changes of SNARE
      proteins levels and thus impaired GLUT-4 displacement can be one of the
      etiological causes of type 2 diabetes. Due to changes in the expression of these
      proteins in diabetes, the aim of this study was to investigate the effect of the
      natural compound resveratrol with anti-diabetic properties on impaired expression
      of SNARE proteins in type 2 diabetes. METHODS: Forty male Wistar rats were used
      in this study. Type 2 diabetes was induced by administering a single dose of
      streptozotocin and nicotinamide. The expression of SNAP-23, syntaxin-4 and VAMP-2
      proteins were assessed using real-time qRT-PCR. Also, some biochemical parameters
      were examined, including fasting blood glucose, insulin levels and insulin
      resistance. RESULTS: The results of this study showed that, resveratrol
      supplementation increased blood insulin level, reduced the fasting blood glucose,
      and improved the insulin resistance. In addition, resveratrol supplementation
      increased the expression of SNAP-23, syntaxin-4 and VAMP-2 proteins that involved
      in GLUT-4 transport in adipose tissue of diabetic rats. CONCLUSION: Final results
      showed that SNARE proteins expression is significantly reduced in diabetic rats
      and treatment with resveratrol supplementation is associated with the increased
      expression of these proteins.

PMID- 25999626
TI  - The role of anion exchanger on pulmonary vascular response to sustained alveolar
      hypoxia in the isolated perfused rabbit lung.
AB  - BACKGROUND: Some respiratory diseases may induce alveolar hypoxia thereby hypoxic
      pulmonary vasoconstriction (HPV). However, the mechanisms of this physiologic
      phenomenon are not fully understood. This study was the first to investigate the
      role of anion exchanger in sustained HPV. METHODS: Experiments were performed in
      the isolated perfused rabbit lung. After preparation, the lungs were divided into
      six groups: two DIDS (4,4-diisothiocyanostilbene 2,2-disulfonic acid, anion
      exchanger inhibitor)-treated [200 uM (n=5) or 400 uM (n=3)] hypoxic groups, two
      HCO3 (-) free hypoxic groups, one control hypoxic group (n=7) and one control
      normoxic group (n=4). DIDS were added to the perfusate at 10 minutes before
      starting the experiments. In the HCO3 (-) free groups, HEPES (4-(2
      Hydroxyethyl)piperazine-1-ethanesulfonic acid) were added to the perfusate
      instead of bicarbonate. Furthermore, in the HEPES1 (n=4) and HEPES2 (n=4) groups,
      the lungs were ventilated with hypoxic gas with or without CO2, respectively.
      RESULTS: Ventilation of the lungs with hypoxic gas resulted in biphasic HPV, the
      acute (0-20 minutes) and sustained (20-60 minutes) phases. No alteration in both
      phases of HPV was detected by DIDS (200 uM). However, DIDS (400 uM), extended the
      ascending part of acute HPV until min 24. Both phases of HPV were decreased in
      the HEPES1 group. However, in the HEPES 2 group, HPV tended to increase during
      the rising part of the acute phase of HPV. CONCLUSIONS: Since DIDS (400 uM)
      extended acute phase of HPV, and HCO3 (-) free perfusate buffer enhanced rising
      phase of it, therefore it can be suggested that anion exchanger may modulate HPV
      especially during the acute phase. The abstract of this article was presented as
      a poster in the congress of European Respiratory Society (ERS) on Monday, 08
      September 2014, Munich, Germany and was published in the ERJ September 1, 2014
      vol. 44 no. Suppl 58 P2343.

PMID- 25999627
TI  - Can we Replace Arterial Blood Gas Analysis by Pulse Oximetry in Neonates with
      Respiratory Distress Syndrome, who are Treated According to INSURE Protocol?
AB  - Neonates with respiratory distress syndrome (RDS), who are treated according to
      INSURE protocol; require arterial blood gas (ABG) analysis to decide on
      appropriate management. We conducted this study to investigate the validity of
      pulse oximetry instead of frequent ABG analysis in the evaluation of these
      patients. From a total of 193 blood samples obtained from 30 neonates <1500 grams
      with RDS, 7.2% were found to have one or more of the followings: acidosis,
      hypercapnia, or hypoxemia. We found that pulse oximetry in the detection of
      hyperoxemia had a good validity to appropriately manage patients without blood
      gas analysis. However, the validity of pulse oximetry was not good enough to
      detect acidosis, hypercapnia, and hypoxemia. 

PMID- 25999628
TI  - Application of McCoy Cell Line for Propagation of Herpes Simplex Virus Type 1.
AB  - Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are members of the
      Herpesviridae family. About 40% to 80% of the world populations are infected with
      HSV and its prevalence is high in Iran. The high prevalence of this virus in the
      community and the ability of the virus in causing fatal diseases among
      immunocompromised patients, have encouraged studies to be performed on HSV and
      suitable cell lines which supports the propagation of HSV. The aim of this study
      was to evaluate the suitability of McCoy cell line in the isolation and
      propagation of HSV. An isolated wild-type HSV-1 was obtained from the labial
      vesicles of a 29-year-old patient who was referred to Ghaem Hospital (Mashhad,
      Iran). The virus was inoculated in McCoy cell monolayer cells and its titer was
      calculated by 50% tissue culture infectious dose (TCID50) method. Cytopathic
      effects (CPE) of HSV on McCoy cells appeared about 20 hours after the infection
      of cells. Titer of the virus was 10(-5.25) TCID50/ml. Our data showed that the
      McCoy cell line supported the propagation of HSV in high titer. This was the
      first study that used McCoy cell line for the isolation and propagation of HSV-1.
      McCoy cell line could be used, as a proper cell line of HSV, for various studies
      in the future. 

PMID- 25999629
TI  - Tracing of helicobacter pylori in patients of otitis media with effusion by
      polymerase chain reaction.
AB  - Otitis media with effusion (OME) is one of the most common causes of hearing loss
      (HL) in children. It has been reported that several factors such as eustachian
      tube dysfunction, insufficiencies in the aeration of the mastoid cells,
      allergies, immunity, and infections play an important role in the etiology of the
      disease. Little is known about the role of Helicobacter pylori (H. pylori) in
      extragastric diseases. Because of the near location of the nose, sinuses,
      tonsils, and adenoids to the eustachian tube and middle ear, we believe it is
      possible to have H. pylori in the middle ear. The present study was designed to
      investigate the presence of H. pylori by polymerase chain reaction (PCR) in the
      middle ear effusion of patients with OME. The study was performed on 21 patients,
      19 patients were affected bilaterally, and 2 patients were affected unilaterally,
      from which 40 specimens were collected. OME was diagnosed through findings by
      otoscopic examination and tympanogram. The middle ear fluid samples were
      collected under sterile conditions. A total of 40 samples was stored at -80
      degrees C until analyzed by PCR assay. From 40 specimens, 2 specimens were
      serosal and 38 specimens were mucoid. PCR results of the study in assays for
      Helicobacter pylori were not positive in all collected specimens. Overall,
      probably there was no H. pylori organism in free-floating form and thus could not
      be detected by PCR. 

PMID- 25999630
TI  - Secondary Involvement of the Mandible due to Basal Cell Carcinoma: A Case Report.
AB  - Basal cell carcinoma (BCC) is the most common cutaneous malignancy among
      Caucasians. Rare examples of aggressive and neglected BCC have been reported.
      Here we report a unique case of a neglected BCC with significant jaw involvement.
      A 50-year-old female, referred by an otorhinologist, presented with a large ulcer
      on her chin, which was extended to her mandibular vestibule. The ulcer was 9*5.5
      cm in size, and tissue destruction, necrosis was observed in the central portion,
      and the mandibular bone was exposed. On intraoral examination, tooth mobility and
      severe bone loss were evident. Due to the primary cutaneous origin of the lesion,
      BCC was considered as preliminary diagnosis. Biopsy was performed and diagnosis
      of BCC was confirmed. The diseased mandibular bone was resected and reconstructed
      with a surgical plate. The soft tissue defect was reconstructed with
      deltopectoral flap. The patient refused secondary stage plastic surgery. Although
      BCC is not a lethal malignancy, if left untreated and neglected, it can result in
      severe destruction, disfigurement, and even mortality. 

PMID- 25999631
TI  - Langerhans cell histiocytosis followed by hodgkin lymphoma: a case report.
AB  - Langerhans cell histiocytosis (LCH) is a rare neoplasm defined as the
      proliferation of bone marrow langerhans cells, which is a kind of dendritic
      cells. The major pathological features of LCH are expression of CD1a and S100 as
      well as Birbeck granules. Its presentation can differ from a mild bone lesion to
      a multi-systemic evolved malignant neoplasm; however, the latter outcome is
      almost rare. Thus, LCH is mostly known as a benign neoplasm. In this study, we
      present a case of LCH followed by Hodgkin lymphoma (HL). Accompaniment of this
      disease with malignant lymphoma is rare and considered as case report. Several
      cases in which malignant lymphoma occurred prior to LCH are reported; however,
      few cases can be found with LCH followed by malignant lymphomas. 

PMID- 25999632
TI  - Metastasis of lung adenocarcinoma to the gingiva: a rare case report.
AB  - Metastatic tumors account for 1% of all oral malignancies. Metastasis to jaw
      bones is common, particularly in the mandible, rare in the oral soft tissues, and
      account for only 0.1% of oral malignancies. The majority of metastatic cases
      (70%) reported in the literature have primary tumors located in the lung, breast,
      kidney, and colon. Metastasis is a biological complex process that involves
      detachment from the surrounding cells, regulation of cell motility, invasion,
      survival, proliferation, and evasion of the immune system. Clinical presentation
      of metastatic tumors is variable, which may create diagnostic dilemma or may lead
      to erroneous diagnosis. Metastatic tumors clinically mimic as dental infections.
      Metastasis to the oral soft tissue from lung cancer, especially gingiva is a rare
      condition. Metastasis to the gingiva can affect the oral function, speech, and
      nutrition. Most of the cases in the literature reported that lesion presented in
      oral soft tissues before the diagnosis of primary tumors. Here we report a case
      of 62-year-old male patient with metastasis from lung to the gingiva, where the
      metastasis was detected before primary tumor. 

PMID- 25999633
TI  - Prevalence of neonatal hyperphenylalaninemia in yazd province, iran.

PMID- 25999634
TI  - Complete radiologic response in metastatic castration-resistant prostate cancer
      treated with cabazitaxel.

PMID- 25999635
TI  - Leader-Member Exchange across two hierarchical levels of leadership: concurrent
      influences on work characteristics and employee psychological health.
AB  - Leader-Member Exchange (LMX) theory suggests that the quality of the leader
      employee relationship is linked to employee psychological health. Leaders who
      reside at different hierarchical levels have unique roles and spheres of
      influence and potentially affect employees' work experiences in different ways.
      Nevertheless, research on the impact of leadership on employee psychological
      health has largely viewed leaders as a homogeneous group. Expanding on LMX
      theory, we argue that (1) LMX sourced at the levels of the line manager (LM) and
      senior management (SM) team will be differentially linked to employee
      psychological health (assessed as worn-out) and that (2) these relationships will
      be mediated by perceived work characteristics (reward and recognition, workload
      management, quality of relationships with colleagues and physical environment).
      Structural equation modelling on data from 337 manual workers partially supported
      the hypotheses. Perceptions of the physical environment mediated the relationship
      between LMX at the LM level and employee psychological health, whereas
      perceptions of workload management mediated the relationship between LMX at the
      SM level and psychological health. These findings corroborate arguments that
      leaders are not a uniform group and as such the effects of LMX on employees will
      depend on leadership hierarchy. Implications for expanding leadership theory are
      discussed.

PMID- 25999636
TI  - Language and iconic gesture use in procedural discourse by speakers with aphasia.
AB  - Background: Conveying instructions is an everyday use of language, and gestures
      are likely to be a key feature of this. Although co-speech iconic gestures are
      tightly integrated with language, and people with aphasia (PWA) produce
      procedural discourses impaired at a linguistic level, no previous studies have
      investigated how PWA use co-speech iconic gestures in these contexts. Aims: This
      study investigated how PWA communicated meaning using gesture and language in
      procedural discourses, compared with neurologically healthy people (NHP). We
      aimed to identify the relative relationship of gesture and speech, in the context
      of impaired language, both overall and in individual events. Methods &
      Procedures: Twenty-nine PWA and 29 NHP produced two procedural discourses. The
      structure and semantic content of language of the whole discourses were analysed
      through predicate argument structure and spatial motor terms, and gestures were
      analysed for frequency and semantic form. Gesture and language were analysed in
      two key events, to determine the relative information presented in each modality.
      Outcomes & Results: PWA and NHP used similar frequencies and forms of gestures,
      although PWA used syntactically simpler language and fewer spatial words. This
      meant, overall, relatively more information was present in PWA gesture. This
      finding was also reflected in the key events, where PWA used gestures conveying
      rich semantic information alongside semantically impoverished language more often
      than NHP. Conclusions: PWA gestures, containing semantic information omitted from
      the concurrent speech, may help listeners with meaning when language is impaired.
      This finding indicates gesture should be included in clinical assessments of
      meaning-making.

PMID- 25999637
TI  - Off to a good start: A comparative study of changes in men's first job prospects
      in East Asia.
AB  - Research on young adults' transition to the labor market rarely investigates how
      nation-level institutional arrangements shape changes over time. In particular, a
      systematic comparison of shifts in young adults' job opportunities in East Asia
      is virtually absent. Using comparable data from Japan, Korea, and Taiwan, we
      examine cohort differences in the timing, quality, and stability of men's first
      jobs. The results indicate overall declines in first occupational attainment for
      men in all three countries, but the main driving force for the decrease in Japan
      differs from that in Korea and Taiwan. Whereas macroeconomic pressure fully
      explains the decline in Japanese men's first occupational attainment, educational
      expansion accounts for a considerable part of the declines for men in Korea and
      Taiwan. Moreover, educational expansion has eroded better-educated men's
      advantages in speedily transitioning from school to work in Taiwan, but it has
      not had a similar effect on Japanese men. We argue that Japan's employment
      system, coupled with a fair amount of institutional ties between schools and
      firms, has shielded young men from the pressure of educational expansion, making
      the trends about their early-career outcomes different from those of their
      counterparts in Korea and Taiwan. The different degrees to which firm internal
      labor markets have been adopted in Japan, Korea, and Taiwan also explain how
      increasing macroeconomic pressure has different impacts on men's first job
      stability in East Asia.

PMID- 25999638
TI  - Characterization of tissue optical properties for prostate PDT using interstitial
      diffuse optical tomography.
AB  - Photodynamic therapy (PDT) is an important treatment modality for localized
      diseases such as prostate cancer. In prostate PDT, light distribution is an
      important factor because it is directly related to treatment efficacy. During
      PDT, light distribution is determined by tissue optical property distributions
      (or heterogeneity). In this study, an interstitial diffuse optical tomography
      (iDOT) method was used to characterize optical properties in tissues. Optical
      properties (absorption and reduced scattering coefficients) of the prostate gland
      were reconstructed by solving the inverse problem using an adjoint model based on
      diffusion equation using a modified matlab public user code NIRFAST. In the
      modified NIRFAST method, linear sources were modeled for the reconstruction.
      Cross talking between absorption coefficients and reduced scattering coefficients
      were studied to have minimal effect, and a constrained optical property method
      (set either absorption coefficient or reduced scattering coefficient to be
      homogeneous) is also studied. A prostate phantom with optical anomalies was used
      to verify the iDOT method. The reconstructed results were compared with the known
      optical properties, and the spatial distribution of optical properties for this
      phantom was successfully reconstructed.

PMID- 25999639
TI  - Maximizing fluence rate and field uniformity of light blanket for intraoperative
      PDT.
AB  - A light blanket is designed with a system of cylindrically diffusing optical
      fibers, which are spirally oriented. This 25*30 cm rectangular light blanket is
      capable of providing uniform illumination during intraoperative photodynamic
      therapy. The flexibility of the blanket proves to be extremely beneficial when
      conforming to the anatomical structures of the patient being treated. Previous
      tests of light distribution from the blanket have shown significant loss of
      intensity with the length of the fiber. This can be improved through the use of
      an optical adaptor which will be able to match the numerical aperture of the
      laser source to the numerical aperture of the blanket fiber; thus transmitting a
      higher percentage of light.

PMID- 25999640
TI  - Monte Carlo simulation of light fluence calculation during pleural PDT.
AB  - A thorough understanding of light distribution in the desired tissue is necessary
      for accurate light dosimetry in PDT. Solving the problem of light dose depends,
      in part, on the geometry of the tissue to be treated. When considering PDT in the
      thoracic cavity for treatment of malignant, localized tumors such as those
      observed in malignant pleural mesothelioma (MPM), changes in light dose caused by
      the cavity geometry should be accounted for in order to improve treatment
      efficacy. Cavity-like geometries demonstrate what is known as the "integrating
      sphere effect" where multiple light scattering off the cavity walls induces an
      overall increase in light dose in the cavity. We present a Monte Carlo simulation
      of light fluence based on a spherical and an elliptical cavity geometry with
      various dimensions. The tissue optical properties as well as the non-scattering
      medium (air and water) varies. We have also introduced small absorption inside
      the cavity to simulate the effect of blood absorption. We expand the MC
      simulation to track photons both within the cavity and in the surrounding cavity
      walls. Simulations are run for a variety of cavity optical properties determined
      using spectroscopic methods. We concluded from the MC simulation that the light
      fluence inside the cavity is inversely proportional to the surface area.

PMID- 25999641
TI  - A Theoretical and Experimental Examination of Fluorescence in Enclosed Cavities.
AB  - Photosensitizer fluorescence emitted during photodynamic therapy (PDT) is of
      interest for monitoring the local concentration of the photosensitizer and its
      photobleaching. In this study, we use Monte Carlo (MC) simulations to evaluate
      the relationship between treatment light and fluorescence, both collected by an
      isotropic detector placed on the surface of the tissue. In treatment of the
      thoracic and peritoneal cavities, the light source position changes continually.
      The MC program is designed to simulate an infinitely broad photon beam incident
      on the tissue at various angles to determine the effect of angle. For each of the
      absorbed photons, a fixed number of fluorescence photons are generated and
      traced. The theoretical results from the MC simulation show that the angle theta
      has little effect on both the measured fluorescence and the ratio of fluorescence
      to diffuse reflectance. However, changes in the absorption and scattering
      coefficients, MUa and [Formula: see text], do cause the fluorescence and ratio to
      change, indicating that a correction for optical properties will be needed for
      absolute fluorescence quantification. Experiments in tissue-simulating phantoms
      confirm that an empirical correction can accurately recover the sensitizer
      concentration over a physiologically relevant range of optical properties.

PMID- 25999642
TI  - A theoretical comparison of macroscopic and microscopic modeling of singlet
      oxygen during Photofrin and HPPH mediated-PDT.
AB  - Mathematic models were developed to simulate the complex dynamic process of
      photodynamic therapy (PDT). Macroscopic or microscopic modeling of singlet oxygen
      (1O2) is particularly of interest because it is the major cytotoxic agent causing
      biological effects during PDT. Our previously introduced macroscopic PDT model
      incorporates the diffusion equation for the light propagation in tissue and the
      macroscopic kinetic equations for the production of the 1O2. The distance
      dependent distribution of 3O2 and reacted 1O2 can be numerically calculated using
      finite-element method (FEM). We recently improved the model to include
      microscopic kinetic equations of oxygen diffusion from uniformly distributed
      blood vessels and within tissue. In the model, the cylindrical blood capillary
      has radius in the range of 2-5 MUm and a mean length of 300 MUm, and supplies
      oxygen into tissue. The blood vessel network is assumed to form a 2-D square grid
      perpendicular to a linear light source. The spacing of the grid is 60 MUm. Oxygen
      can also diffuse along the radius and the longitudinal axial of the cylinder
      within tissue. The oxygen depletion during Photofrin-PDT can be simulated using
      both macroscopic and microscopic approaches. The comparison of the simulation
      results have reasonable agreements when velocity of blood flow is reduced during
      PDT.

PMID- 25999643
TI  - A novel near real-time laser scanning device for geometrical determination of
      pleural cavity surface.
AB  - During HPPH-mediated pleural photodynamic therapy (PDT), it is critical to
      determine the anatomic geometry of the pleural surface quickly as there may be
      movement during treatment resulting in changes with the cavity. We have developed
      a laser scanning device for this purpose, which has the potential to obtain the
      surface geometry in real-time. A red diode laser with a holographic template to
      create a pattern and a camera with auto-focusing abilities are used to scan the
      cavity. In conjunction with a calibration with a known surface, we can use
      methods of triangulation to reconstruct the surface. Using a chest phantom, we
      are able to obtain a 360 degree scan of the interior in under 1 minute. The chest
      phantom scan was compared to an existing CT scan to determine its accuracy. The
      laser-camera separation can be determined through the calibration with 2mm
      accuracy. The device is best suited for environments that are on the scale of a
      chest cavity (between 10cm and 40cm). This technique has the potential to produce
      cavity geometry in real-time during treatment. This would enable PDT treatment
      dosage to be determined with greater accuracy. Works are ongoing to build a
      miniaturized device that moves the light source and camera via a fiber-optics
      bundle commonly used for endoscopy with increased accuracy.

PMID- 25999644
TI  - Parameter Determination for Singlet Oxygen Modeling of BPD-Mediated PDT.
AB  - Photodynamic therapy (PDT) offers a cancer treatment modality capable of
      providing minimally invasive localized tumor necrosis. To accurately predict PDT
      treatment outcome based on pre-treatment patient specific parameters, an explicit
      dosimetry model is used to calculate apparent reacted 1O2 concentration ([1O2]rx)
      at varied radial distances from the activating light source inserted into tumor
      tissue and apparent singlet oxygen threshold concentration for necrosis ([1O2]rx,
      sd) for type-II PDT photosensitizers. Inputs into the model include a number of
      photosensitizer independent parameters as well as photosensitizer specific
      photochemical parameters xi, sigma, and beta. To determine the specific
      photochemical parameters of benzoporphyrin derivative monoacid A (BPD), mice were
      treated with BPD-PDT with varied light source strengths and treatment times. All
      photosensitizer independent inputs were assessed pre-treatment and average
      necrotic radius in treated tissue was determined post-treatment. Using the
      explicit dosimetry model, BPD specific xi, sigma, and beta photochemical
      parameters were determined which estimated necrotic radii similar to those
      observed in initial BPD-PDT treated mice using an optimization algorithm that
      minimizes the difference between the model and that of the measurements.
      Photochemical parameters for BPD are compared with those of other known
      photosensitizers, such as Photofrin. The determination of these BPD specific
      photochemical parameters provides necessary data for predictive treatment outcome
      in clinical BPD-PDT using the explicit dosimetry model.

PMID- 25999645
TI  - PDT dose dosimetry for pleural photodynamic therapy.
AB  - PDT dose is the product of the photosensitizer concentration and the light
      fluence in target tissue. Although existing systems are capable of measuring the
      light fluence in vivo, the concurrent measurement of photosensitizer in the
      treated tissue so far has been lacking. We have developed and tested a new method
      to simultaneously acquire light dosimetry and photosensitizer fluorescence data
      via the same isotropic detector, employing treatment light as the excitation
      source. A dichroic beamsplitter is used to split light from the isotropic
      detector into two fibers, one for light dosimetry, the other, after the 665 nm
      treatment light is removed by a band-stop filter, to a spectrometer for
      fluorescence detection. The light fluence varies significantly during treatment
      because of the source movement. The fluorescence signal is normalized by the
      light fluence measured at treatment wavelength. We have shown that the absolute
      photosensitizer concentration can be obtained by an optical properties correction
      factor and linear spectral fitting. Tissue optical properties are determined
      using an absorption spectroscopy probe immediately before PDT at the same sites.
      This novel method allows accurate real-time determination of delivered PDT dose
      using existing isotropic detectors, and may lead to a considerable improvement of
      PDT treatment quality compared to the currently employed systems. Preliminary
      data in patient studies is presented.

PMID- 25999646
TI  - Light dosimetry and dose verification for pleural PDT.
AB  - In-vivo light dosimetry for patients undergoing photodynamic therapy (PDT) is
      critical for predicting PDT outcome. Patients in this study are enrolled in a
      Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell
      lung cancer with pleural effusion. They are administered 4mg per kg body weight
      HPPH 48 hours before the surgery and receive light therapy with a fluence of 15
      45 J/cm2 at 661 and 665nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2)
      are monitored at 7 sites during the light treatment delivery using isotropic
      detectors. Light fluence (rate) delivered to patients is examined as a function
      of treatment time, volume and surface area. In a previous study, a correlation
      between the treatment time and the treatment volume and surface area was
      established. However, we did not include the direct light and the effect of the
      shape of the pleural surface on the scattered light. A real-time infrared (IR)
      navigation system was used to separate the contribution from the direct light. An
      improved expression that accurately calculates the total fluence at the cavity
      wall as a function of light source location, cavity geometry and optical
      properties is determined based on theoretical and phantom studies. The
      theoretical study includes an expression for light fluence rate in an elliptical
      geometry instead of the spheroid geometry used previously. The calculated light
      fluence is compared to the measured fluence in patients of different cavity
      geometries and optical properties. The result can be used as a clinical guideline
      for future pleural PDT treatment.

PMID- 25999647
TI  - Real-time treatment feedback guidance of Pleural PDT.
AB  - Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with
      lung-sparing surgical treatment for mesothelioma with remarkable results. In the
      current intrapleural PDT protocol, a moving fiber-based point source is used to
      deliver the light and the light dose are monitored by 7 detectors placed in the
      pleural cavity. To improve the delivery of light dose uniformity, an infrared
      (IR) camera system is used to track the motion of the light sources. A treatment
      planning system uses feedback from the detectors as well as the IR camera to
      update light fluence distribution in real-time, which is used to guide the light
      source motion for uniform light dose distribution. We have improved the GUI of
      the light dose calculation engine to provide real-time light fluence distribution
      suitable for guiding the surgery to delivery light more uniformly. A dual
      correction method is used in the feedback system, so that fluence calculation can
      match detector readings using both direct and scatter light models. An improved
      measurement device is developed to automatically acquire laser position for the
      point source. Comparison of the effects of the guidance is presented in phantom
      study.

PMID- 25999648
TI  - Determination of tissue optical properties in PDT treated Head & Neck patients.
AB  - Determination of optical properties (absorption (MUa) and scattering (MUs')
      coefficients) in human tissue is important when it comes to accurate calculation
      of fluence rate in and around tissue area. ALA application to the tissue induces
      production of protoporphyrin IX when activated by red light. Changes in the
      tissue optical properties can send information such as treatment outcome and
      tissue drug concentration. Patients in this study were treated with PDT for head
      and neck mucosal dysplasia. They were enrolled in a phase I study of escalating
      light doses and oral ALA with 60mg/kg. Red light at 630nm was administered to the
      tumor from a laser. The light dose was escalated from 50-200J/cm2 with a measured
      fluence rate at tissue surface of 100mW/cm2. We developed a light detection
      device for the purpose of determining optical properties in vivo using the semi
      infinite method. The light detection device consists of two parallel, placed 5mm
      apart. In one of the catheters a 2 mm long linear diffusing light source is
      placed while in the second catheter, a calibrated isotropic detector is placed.
      The detector is scanned along the length of the light source containing catheter.
      Scans are done with the device placed on the treatment area (tumor) and on the
      normal tissue. Optical properties were measured in-vivo before and after PDT
      delivery for both normal tissue and tumor.

PMID- 25999649
TI  - Comparison of PDT parameters for RIF and H460 tumor models during HPPH-mediated
      PDT.
AB  - Singlet oxygen (1O2) is the major cytotoxic species producing PDT effects, but it
      is difficult to monitor in vivo due to its short life time in real biological
      environments. Mathematical models are then useful to calculate 1O2 concentrations
      for PDT dosimetry. Our previously introduced macroscopic model has four PDT
      parameters: xi, sigma, beta and g describing initial oxygen consumption rate,
      ratio of photobleaching to reaction between 1O2 and cellular targets, ratio of
      triplet state (T) phosphorescence to reaction between T and oxygen (3O2), and
      oxygen supply rate to tissue, respectively. In addition, the model calculates a
      fifth parameter, threshold 1O2 dose ([1O2]rx,sd). These PDT parameters have been
      investigated for HPPH using radiation-induced fibrosarcoma (RIF) tumors in an in
      vivo C3H mouse model. In recent studies, we additionally investigated these
      parameters in human non-small cell lung carcinoma (H460) tumor xenografts, also
      using HPPH-mediated PDT. In-vivo studies are performed with nude female mice with
      H460 tumors grown intradermally on their right shoulders. HPPH (0.25 mg/kg) is
      injected i.v. at 24 hours prior to light delivery. Initial in vivo HPPH
      concentration is quantified via interstitial HPPH fluorescence measurements after
      correction for tissue optical properties. Light is delivered by a linear source
      at various light doses (12-50 J/cm) with powers ranging from 12 to 150 mW per cm
      length. The necrosis radius is quantified using ScanScope after tumor sectioning
      and hematoxylin and eosin (H&E) staining. The macroscopic optimization model is
      used to fit the results and generate four PDT parameters. Initial results of the
      parameters for H460 tumors will be reported and compared with those for the RIF
      tumor.

PMID- 25999650
TI  - Diffuse optical tomography using multichannel robotic platform for interstitial
      PDT.
AB  - In the operating room, time is extremely precious, and the speed of one's data
      acquisition system often determines whether the data will be taken or not. Our
      multichannel robotic platform addresses this issue by optimizing source and
      detector scanning procedures. Up to 16 fibers can be moved independently with
      resolution of 0.05 mm and speed of 50 mm/s using motors with position feedback.
      The initial fiber alignment employs a light beam/optical detector system for
      identical positioning of all motors. Peak and edge detection algorithms, for
      point and linear sources, are used with multiple fibers simultaneously for fast
      realignment of sources and detectors. The robotic platform is used to perform
      Diffuse Optical Tomography (DOT) measurements in solid prostate phantoms with
      both homogenous and inhomogeneous Optical Properties (OP). Correct positioning is
      critical for the accurate recovery of the OP. The light fluence rate distribution
      is determined by scanning multiple detector fibers simultaneously along lit
      linear sources placed throughout the phantom volume inside catheter needles. The
      scanning time for the entire DOT is about 10 seconds after the initial alignment.
      The OP distribution reconstruction is based on the steady-state light diffusion
      equation. The inverse interstitial DOT problem is solved using NIRFAST. The
      optical properties are recovered by iterative minimization of the difference
      between measured and calculated light fluence rates. Recovered OP agree with the
      actual values within 10%. The OP corrections are used to significantly improve
      light fluence accuracy for the entire volume of bulk tumor.

PMID- 25999651
TI  - Comparison of singlet oxygen threshold dose for PDT.
AB  - Macroscopic modeling of singlet oxygen (1O2) is of particular interest because it
      is the major cytotoxic agent causing biological effects for type II
      photosensitizers during PDT. We have developed a macroscopic model to calculate
      reacted singlet oxygen concentration ([1O2]rx for PDT. An in-vivo RIF tumor mouse
      model is used to correlate the necrosis depth to the calculation based on
      explicit PDT dosimetry of light fluence distribution, tissue optical properties,
      and photosensitizer concentrations. Inputs to the model include 4 photosensitizer
      specific photochemical parameters along with the apparent singlet oxygen
      threshold concentration. Photosensitizer specific model parameters are determined
      for several type II photosensitizers (Photofrin, BPD, and HPPH). The singlet
      oxygen threshold concentration is approximately 0.41 - 0.56 mM for all three
      photosensitizers studied, assuming that the fraction of singlet oxygen generated
      that interacts with the cell is (f = 1). In comparison, value derived from other
      in-vivo mice studies is 0.4 mM for mTHPC. However, the singlet oxygen threshold
      doses were reported to be 7.9 and 12.1 mM for a multicell in-vitro EMT6/Ro
      spheroid model for mTHPC and Photofrin PDT, respectively. The sensitivity of
      threshold singlet oxygen dose for our experiment is examined. The possible
      influence of vascular vs. apoptotic cell killing mechanism on the singlet oxygen
      threshold dose is discussed using the BPD with different drug-light intervals 3
      hrs vs. 15 min. The observed discrepancies between different experiments warrant
      further investigation to explain the cause of the difference.

PMID- 25999652
TI  - Anisotropic modeling for IR navigation-based PDT dosimetry.
AB  - An infrared (IR) camera system has been developed for use in pleural photodynamic
      therapy (PDT). This system was introduced to pleural PDT to provide uniform light
      dose distribution to ensure predictable PDT outcome. Light is delivered through a
      fiber that is in an endotracheal (ET) tube filled with Intralipid as scattering
      media. A tracking tool is attached to the ET tube to monitor the position of the
      optical fiber based point source. An anisotropic light distribution model is
      introduced to correct the angle dependent light distribution due to a capped end
      by design of the ET tube, which scatters light differently than the sides. In
      this study, the anisotropic nature of the balloon was characterized and
      incorporated into the calculation for light fluence during treatment. This model
      is verified by the light dose calculation from a phantom study. Furthermore, a
      new tracking tool was designed with multiple faces to increase the angular field
      of view and thus collect more viable data during treatment. The new tracking tool
      is directly entered into the ET tube with the light delivering fiber, thus
      eliminating the need to calibrate the laser source position prior to treatment
      via an optimization method. With this improved system, the calculated light
      fluence and the measured isotropic detector readings are more accurately matched.

PMID- 25999653
TI  - Parameter determination for BPD mediated vascularPDT.
AB  - The cell killing mechanism of benzoporphyrin derivative monoacid ring A (BPD) is
      known to be predominantly apoptotic or vascular, depending on the drug-light
      interval (DLI). With a 3 hour DLI, necrosis develops secondary to tumor cell
      damage, while with a 15 minute DLI, necrosis results from treatment-created
      vascular damage. The purpose of this study is to examine if the different
      mechanisms of cell death will affect the photochemical parameters for the
      macroscopic singlet oxygen model. Using the RIF model of murine fibrosarcoma, we
      determined the four photochemical parameters (xi, sigma, beta, gamma) and the
      threshold singlet oxygen dose for BPD-mediated PDT through evaluation of the
      extent of tumor necrosis as a function of PDT fluence rate and total fluence.
      Mice were treated with a linear source at fluence rates from 12-150 mW/cm and
      total fluences from 24-135 J/cm. BPD was administered at 1mg/kg with a 15 minute
      DLI, followed by light delivery at 690nm. Tumors were excised at 24 hours after
      PDT and necrosis was analyzed via H&E staining. The in-vivo BPD drug
      concentration is determined to be in the range of 0.05-0.30 MUM. The
      determination of these parameters specific for BPD and the 15 minute DLI provides
      necessary data for predicting treatment outcome in clinical BPD-mediated PDT.
      Photochemical parameters will be compared between 1mg/kg DLI 3 hours and 1mg/kg
      DLI 15 minutes.

PMID- 25999654
TI  - Real-time treatment light dose guidance of Pleural PDT: an update.
AB  - The goal of this study was to develop and improve an infrared (IR) navigation
      system to deliver light dose uniformly during intracavitory PDT by tracking the
      movement of the light source and providing real-time feedback on the light
      fluence rate on the entire cavity surface area. In the current intrapleural PDT
      protocol, several detectors placed in selected locations in the pleural cavity
      monitor the light doses. To improve the delivery of light dose uniformity, an IR
      camera system is used to track the motion of the light source as well as the
      surface contour of the pleural cavity. Monte-Carlo simulation is used to improve
      the calculation algorithm for the effect of light that undergoes multiple
      scattering along the surface in addition to an improvement of the direct light
      calculation using an improved model that accounts for the anisotropy of the light
      from the light source.

PMID- 25999655
TI  - In vivo outcome study of BPD-mediated PDT using a macroscopic singlet oxygen
      model.
AB  - Macroscopic modeling of the apparent reacted singlet oxygen concentration
      ([1O2]rx) for use with photodynamic therapy (PDT) has been developed and studied
      for benzoporphryin derivative monoacid ring A (BPD), a common photosensitizer.
      The four photophysical parameters (xi, sigma, beta, delta) and threshold singlet
      oxygen dose ([1O2]rx,sh) have been investigated and determined using the RIF
      model of murine fibrosarcomas and interstitial treatment delivery. These
      parameters are examined and verified further by monitoring tumor growth post-PDT.
      BPD was administered at 1 mg/kg, and mice were treated 3 hours later with fluence
      rates ranging between 75 - 150 mW/cm2 and total fluences of 100 - 350 J/cm2.
      Treatment was delivered superficially using a collimated beam. Changes in tumor
      volume were tracked following treatment. The tumor growth rate was fitted for
      each treatment condition group and compared using dose metrics including total
      light dose, PDT dose, and reacted singlet oxygen. Initial data showing the
      correlation between outcomes and various dose metrics indicate that reacted
      singlet oxygen serves as a good dosimetric quantity for predicting PDT outcome.

PMID- 25999656
TI  - In-vivo outcome study of HPPH mediated PDT using singlet oxygen explicit
      dosimetry (SOED).
AB  - Type II photodynamic therapy (PDT) is based on the use of photochemical reactions
      mediated through an interaction between a tumor-selective photosensitizer,
      photoexcitation with a specific wavelength of light, and production of reactive
      singlet oxygen. However, the medical application of this technique has been
      limited due to inaccurate PDT dosimetric methods. The goal of this study is to
      examine the relationship between outcome (in terms of tumor growth rate) and
      calculated reacted singlet oxygen concentration ([1O2]rx) after HPPH-mediated PDT
      to compare with other PDT dose metrics, such as PDT dose or total light fluence.
      Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different
      light fluence and fluence rate conditions. Explicit measurements of
      photosensitizer drug concentration and tissue optical properties via fluorescence
      and absorption measurement with a contact probe before and after PDT were taken
      to then quantify total light fluence, PDT dose, and [1O2]rx based on a
      macroscopic model of singlet oxygen. In addition, photobleaching of
      photosenitizer were measured during PDT as a second check of the model. Changes
      in tumor volume were tracked following treatment and compared to the three
      calculated dose metrics. The correlations between total light fluence, PDT dose,
      reacted [1O2]rx and tumor growth demonstrate that [1O2]rx serves as a better
      dosimetric quantity for predicting treatment outcome and a clinically relevant
      tumor growth endpoint.

PMID- 25999658
TI  - Analysis of Serum MicroRNAs as Potential Biomarker in Coronary Bifurcation
      Lesion.
AB  - Recent evidence suggests that cell-derived circulating miRNAs may serve as the
      biomarkers of cardiovascular diseases. However, no study has investigated the
      potential of circulating miRNAs as biomarker for coronary bifurcation lesion. In
      this study, we aimed to characterize the miRNA profiles that could distinguish
      coronary bifurcation lesion and identify potential miRNAs as biomarkers of
      coronary bifurcation lesion. We employed miRNA microarray to screen serum miRNAs
      profiles of patients with coronary bifurcation lesion and coronary nonbifurcation
      lesions. We identified 197 miRNAs differentially expressed, including 150 miRNAs
      upregulated and 47 miRNAs downregulated. We chose 3 miRNAs with significant
      differences for further testing in 200 patients. RT-PCR analysis of serum samples
      confirmed that miR30d was upregulated and miR1246 was downregulated in the serum
      of coronary bifurcation lesion patients compared with nonbifurcation lesion
      patients. Our findings suggest that these miRNAs may have a role in the
      pathogenesis of coronary bifurcation lesion and may represent novel biomarkers
      for the diagnosis and prognosis of coronary bifurcation lesion. 

PMID- 25999657
TI  - Proteomics in cancer biomarkers discovery: challenges and applications.
AB  - With the introduction of recent high-throughput technologies to various fields of
      science and medicine, it is becoming clear that obtaining large amounts of data
      is no longer a problem in modern research laboratories. However, coherent study
      designs, optimal conditions for obtaining high-quality data, and compelling
      interpretation, in accordance with the evidence-based systems biology, are
      critical factors in ensuring the emergence of good science out of these recent
      technologies. This review focuses on the proteomics field and its new
      perspectives on cancer research. Cornerstone publications that have tremendously
      helped scientists and clinicians to better understand cancer pathogenesis; to
      discover novel diagnostic and/or prognostic biomarkers; and to suggest novel
      therapeutic targets will be presented. The author of this review aims at
      presenting some of the relevant literature data that helped as a step forward in
      bridging the gap between bench work results and bedside potentials. Undeniably,
      this review cannot include all the work that is being produced by expert research
      groups all over the world. 

PMID- 25999659
TI  - Comparative Proteomic Analysis of Human Cholangiocarcinoma Cell Lines: S100A2 as
      a Potential Candidate Protein Inducer of Invasion.
AB  - Cholangiocarcinoma (CCA) is a bile duct cancer, commonly found in Asia including
      Thailand and especially in the northeastern region of Thailand. To identify the
      proteins involved in carcinogenesis and metastasis of CCA, protein expression
      profiles of high-invasive KKU-M213 and low-invasive KKU-100 cell lines were
      compared using a comparative GeLC-MS/MS proteomics analysis. A total of 651
      differentially expressed proteins were detected of which 27 protein candidates
      were identified as having functions involved in cell motility. A total of 22
      proteins were significantly upregulated in KKU-M213, whereas 5 proteins were
      downregulated in KKU-M213. S100A2, a calcium-binding protein in S100 protein
      family, is upregulated in KKU-M213. S100A2 is implicated in metastasis
      development in several cancers. The protein expression level of S100A2 was
      verified by Western blot analysis. Intriguingly, high-invasive KKU-M213 cells
      showed higher expression of S100A2 than KKU-100 cells, consistent with proteomic
      data, suggesting that S100A2 may be a key protein involved in the progression of
      CCA. However, the biological function of S100A2 in cholangiocarcinoma remains to
      be elucidated. S100A2 might be a potential biomarker as well as a novel
      therapeutic target in CCA metastasis. 

PMID- 25999660
TI  - Omics-based identification of biomarkers for nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is highly found in
      distinct geographic areas, such as Southeast Asia. The management of NPC remains
      burdensome as the prognosis is poor due to the late presentation of the disease
      and the complex nature of NPC pathogenesis. Therefore, it is necessary to find
      effective molecular markers for early detection and therapeutic measure of NPC.
      In this paper, the discovery of molecular biomarker for NPC through the emerging
      omics technologies including genomics, miRNA-omics, transcriptomics, proteomics,
      and metabolomics will be extensively reviewed. These markers have been shown to
      play roles in various cellular pathways in NPC progression. The knowledge on
      their function will help us understand in more detail the complexity in tumor
      biology, leading to the better strategies for early detection, outcome
      prediction, detection of disease recurrence, and therapeutic approach. 

PMID- 25999661
TI  - Polymorphisms in C-reactive protein and Glypican-5 are associated with lung
      cancer risk and Gartrokine-1 influences Cisplatin-based chemotherapy response in
      a Chinese Han population.
AB  - The role of genetics in progression of cancer is an established fact, and
      susceptibility risk and difference in outcome to chemotherapy may be caused by
      the variation in low-penetrance alleles of risk genes. We selected seven genes
      (CRP, GPC5, ACTA2, AGPHD1, SEC14L5, RBMS3, and GKN1) that previously reported
      link to lung cancer (LC) and genotyped single nucleotide polymorphisms (SNPs) of
      these genes in a case-control study. A protective allele "C" was found in
      rs2808630 of the C-reactive protein (CRP). Model association analysis found
      genotypes "T/C" and "C/C" in the dominant model and genotype "T/C" in the
      overdominant model of rs2808630 associated with reduced LC risk. Gender-specific
      analysis in each model showed that genotypes "T/T" and "C/C" in rs2352028 of the
      Glypican 5 (GPC5) were associated with increased LC risk in males. Logistic
      regression analysis showed "C/T" genotype carriers of rs4254535 in the Gastrokine
      1 (GKN1) had less likelihood to have chemotherapy response. Our results suggest a
      potential association between CRP and GPC5 variants with LC risk; variation in
      GKN1 is associated with chemotherapy response in the Chinese Han population. 

PMID- 25999662
TI  - Suppress to Survive-Implication of Plant Viruses in PTGS.
AB  - In higher plants, evolutionarily conserved processes playing an essential role
      during gene expression rely on small noncoding RNA molecules (sRNA). Within a
      wide range of sRNA-dependent cellular events, there is posttranscriptional gene
      silencing, the process that is activated in response to the presence of double
      stranded RNAs (dsRNAs) in planta. The sequence-specific mechanism of silencing is
      based on RNase-mediated trimming of dsRNAs into translationally inactive short
      molecules. Viruses invading and replicating in host are also a source of dsRNAs
      and are recognized as such by cellular posttranscriptional silencing machinery
      leading to degradation of the pathogenic RNA. However, viruses are not totally
      defenseless. In parallel with evolving plant defense strategies, viruses have
      managed a wide range of multifunctional proteins that efficiently impede the
      posttranscriptional gene silencing. These viral counteracting factors are known
      as suppressors of RNA silencing. The aim of this review is to summarize the role
      and the mode of action of several functionally characterized RNA silencing
      suppressors encoded by RNA viruses directly involved in plant-pathogen
      interactions. Additionally, we point out that the widely diverse functions,
      structures, and modes of action of viral suppressors can be performed by
      different proteins, even in related viruses. All those adaptations have been
      evolved to achieve the same goal: to maximize the rate of viral genetic material
      replication by interrupting the evolutionary conserved plant defense mechanism of
      posttranscriptional gene silencing.

PMID- 25999663
TI  - Origin and speciation of Picea schrenkiana and Piceasmithiana in the Center Asian
      Highlands and Himalayas.
AB  - Elucidating the evolutionary history of current species diversity, especially
      trees with large effective population sizes and long generation times, is a
      complicated exercise confounded by gene flow and incomplete lineage sorting. In
      the present study, we aim to determine the origin and speciation of Picea
      schrenkiana and Picea smithiana using population genetic data from chloroplast
      (cp), mitochondrial (mt), and nuclear (nr) genomes. These two species occur in
      the Central Asian Highlands and Himalayas, respectively, where they are isolated
      from other Asian congeneric species by the Qinghai-Tibet Plateau (QTP) or
      adjacent deserts. Previous studies based on both morphological and molecular
      evidence suggest that they have contrasting phylogenetic relationships with Picea
      likiangensis or Picea wilsonii which are closely related and both located in the
      QTP. We examined genetic variation among 16 loci of three genomes from 30
      populations of these four species. At both cpDNA loci and mtDNA loci, P.
      schrenkiana appeared to be closely related to P. likiangensis, although
      statistical support for this was weak. However, phylogenetic analyses and
      speciation tests based on the nuclear data from 11 loci provided evidence that P.
      schrenkiana and P. smithiana are sister species. These two species diverged
      around five million years ago (Mya) while the divergence between them and the P.
      likiangensis-P. wilsonii clade occurred about 18.4 Mya. We also detected gene
      flow accompanying these speciation events. Our results highlight the complex
      speciation histories of these alpine conifers due to interspecific gene flow
      and/or incomplete lineage sorting, and the importance of the early QTP uplifts in
      promoting the origin of these important conifer species in the Asian highlands.

PMID- 25999664
TI  - Different Gene Expressions of Resistant and Susceptible Hop Cultivars in Response
      to Infection with a Highly Aggressive Strain of Verticillium albo-atrum.
AB  - Verticillium wilt has become a serious threat to hop production in Europe due to
      outbreaks of lethal wilt caused by a highly virulent strain of Verticillium albo
      atrum. In order to enhance our understanding of resistance mechanisms, the fungal
      colonization patterns and interactions of resistant and susceptible hop cultivars
      infected with V. albo-atrum were analysed in time course experiments.
      Quantification of fungal DNA showed marked differences in spatial and temporal
      fungal colonization patterns in the two cultivars. Two differential display
      methods obtained 217 transcripts with altered expression, of which 84 showed
      similarity to plant proteins and 8 to fungal proteins. Gene ontology categorised
      them into cellular and metabolic processes, response to stimuli, biological
      regulation, biogenesis and localization. The expression patterns of 17
      transcripts with possible implication in plant immunity were examined by real
      time PCR (RT-qPCR). Our results showed strong expression of genes encoding
      pathogenesis-related (PR) proteins in susceptible plants and strong upregulation
      of genes implicated in ubiquitination and vesicle trafficking in the incompatible
      interaction and their downregulation in susceptible plants, suggesting the
      involvement of these processes in the hop resistance reaction. In the resistant
      cultivar, the RT-qPCR expression patterns of most genes showed their peak at 20
      dpi and declined towards 30 dpi, comparable to the gene expression pattern of in
      planta detected fungal protein and coinciding with the highest fungal biomass in
      plants at 15 dpi. These expression patterns suggest that the defence response in
      the resistant cultivar is strong enough at 20 dpi to restrict further fungus
      colonization.

PMID- 25999665
TI  - Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer.
AB  - Targeted drug delivery using epidermal growth factor peptide-targeted gold
      nanoparticles (EGFpep-Au NPs) is investigated as a novel approach for delivery of
      photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies
      of PDT show that EGFpep-Au NP-Pc 4 is twofold better at killing tumor cells than
      free Pc 4 after increasing localization in early endosomes. In vivo studies show
      that targeting with EGFpep-Au NP-Pc 4 improves accumulation of fluorescence of Pc
      4 in subcutaneous tumors by greater than threefold compared with untargeted Au
      NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic
      fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in
      vivo that EGFpep-Au NP-Pc 4 impacts biodistribution of the NPs by decreasing the
      initial uptake by the reticuloendothelial system (RES) and by increasing the
      amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly,
      in vivo PDT with EGFpep-Au NP-Pc 4 results in interrupted tumor growth when
      compared with EGFpep-Au NP control mice when selectively activated with light.
      These data demonstrate that EGFpep-Au NP-Pc 4 utilizes cancer-specific biomarkers
      to improve drug delivery and therapeutic efficacy over untargeted drug delivery.

PMID- 25999666
TI  - Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance
      between Coagulation and Fibrinolysis and Inflammatory Mediators.
AB  - Dengue is an infectious disease caused by dengue virus (DENV). In general, dengue
      is a self-limiting acute febrile illness followed by a phase of critical
      defervescence, in which patients may improve or progress to a severe form. Severe
      illness is characterized by hemodynamic disturbances, increased vascular
      permeability, hypovolemia, hypotension, and shock. Thrombocytopenia and platelet
      dysfunction are common in both cases and are related to the clinical outcome.
      Different mechanisms have been hypothesized to explain DENV-associated
      thrombocytopenia, including the suppression of bone marrow and the peripheral
      destruction of platelets. Studies have shown DENV-infected hematopoietic
      progenitors or bone marrow stromal cells. Moreover, anti-platelet antibodies
      would be involved in peripheral platelet destruction as platelets interact with
      endothelial cells, immune cells, and/or DENV. It is not yet clear whether
      platelets play a role in the viral spread. Here, we focus on the mechanisms of
      thrombocytopenia and platelet dysfunction in DENV infection. Because platelets
      participate in the inflammatory and immune response by promoting cytokine,
      chemokine, and inflammatory mediator secretion, their relevance as "immune-like
      effector cells" will be discussed. Finally, an implication for platelets in
      plasma leakage will be also regarded, as thrombocytopenia is associated with
      clinical outcome and higher mortality. 

PMID- 25999669
TI  - Anti-inflammatory natural products.

PMID- 25999668
TI  - Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.
AB  - Cocaine is a commonly abused illicit drug that causes significant morbidity and
      mortality. The most severe and common complications are seizures, ischemic
      strokes, myocardial infarction, and acute liver injury. Here, we demonstrated
      that acute cocaine intoxication promoted seizure along with acute liver damage in
      mice, with intense inflammatory infiltrate. Considering the protective role of
      the endocannabinoid system against cell toxicity, we hypothesized that treatment
      with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid,
      cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg)
      abolished cocaine-induced seizure, yet it did not protect against acute liver
      injury. Using confocal liver intravital microscopy, we observed that CBD (30
      mg/kg) reduced acute liver inflammation and damage induced by cocaine and
      prevented associated seizure. Additionally, we showed that previous liver damage
      induced by another hepatotoxic drug (acetaminophen) increased seizure and
      lethality induced by cocaine intoxication, linking hepatotoxicity to seizure
      dynamics. These findings suggest that activation of cannabinoid system may have
      protective actions on both liver and brain induced by cocaine, minimizing
      inflammatory injury promoted by cocaine, supporting its further clinical
      application in the treatment of cocaine abuse.

PMID- 25999667
TI  - Interleukin-17 and its implication in the regulation of differentiation and
      function of hematopoietic and mesenchymal stem cells.
AB  - Adult stem cells have a great potential applicability in regenerative medicine
      and cell-based therapies. However, there are still many unresolved issues
      concerning their biology, and the influence of the local microenvironment on
      properties of stem cells has been increasingly recognized. Interleukin (IL-) 17,
      as a cytokine implicated in many physiological and pathological processes, should
      be taken into consideration as a part of a regulatory network governing tissue
      associated stem cells' fate. This review is focusing on the published data on the
      effects of IL-17 on the properties and function of hematopoietic and mesenchymal
      stem cells and trying to discuss that IL-17 achieves many of its roles by acting
      on adult stem cells. 

PMID- 25999670
TI  - Molecular and biochemical characterization of recombinant guinea pig tumor
      necrosis factor-alpha.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a cytokine which plays opposing roles
      in the context of infectious disease pathogenesis. TNF-alpha is essential for the
      development of a protective immune response to some pathogens, for example,
      Mycobacterium tuberculosis, by synergizing with other cytokines. However,
      exorbitant or uncontrolled TNF-alpha activity may also drive pathology and
      disease symptoms in many infectious diseases. In order to elucidate the
      beneficial and detrimental roles of TNF-alpha in tuberculosis (TB) and other
      diseases for which the guinea pig is the small animal model of choice,
      recombinant guinea pig (rgp)TNF-alpha has been produced using prokaryotic
      expression systems. However, it is unknown whether posttranslational
      modifications which cannot be made in the prokaryotic expression systems may be
      important for rgpTNF-alpha structure and function. Therefore, we carried out a
      comparative study by expressing rgpTNF-alpha in prokaryotic and eukaryotic
      expression systems and analyzed the eukaryotic-expressed rgpTNF-alpha for the
      presence of posttranslational modifications by subjecting it to NanoLC-MS/MS. We
      conclude that the eukaryotic-expressed rgpTNF-alpha lacks posttranslational
      modifications, and we found no significant difference in terms of the biological
      activity between prokaryotic- and eukaryotic-expressed rgpTNF-alpha. Taken
      together, results from our study show that a prokaryotic expression system can be
      used for generating large amounts of rgpTNF-alpha without concern for the
      biological integrity. 

PMID- 25999671
TI  - Activity of fluconazole and its Cu(II) complex towards Candida species.
AB  - Candida species, although they are present as commensal organisms in the
      digestive tract of healthy individuals, can produce a broad spectrum of serious
      illnesses in compromised hosts. Fluconazole, a water-soluble triazole with
      bioavailability greater than 90 %, has been extensively used to treat a wide
      range of Candida infections. However, a growing resistance of microorganisms in
      the treatment leads to the discovery of new drugs or modifications of existing
      ones. The aim of the present study was to investigate whether coordination of
      Cu(II) ions to fluconazole affects its antifungal activity. The in vitro
      susceptibility tests and antifungal studies were performed with two Candida spp.:
      Candidaglabrata and Candida albicans. Overall, 34 strains of the former and 16
      strains of the latter were treated with fluconazole, its Cu(II) complex and free
      Cu(II) ions. The obtained MIC values in 16 cases of the C. glabrata and in 5
      cases of the C. albicans were lower for the complex in comparison to the drug.
      This implies that the complex is more effective against particular strains than
      the parent drug. The most significant improvement in the complex drug efficacy
      was observed for fluconazole-resistant species.

PMID- 25999672
TI  - Intracellular IL-4, IL-5, and IFN-gamma as the main characteristic of CD4+CD30+ T
      cells after allergen stimulation in patients with vernal keratoconjunctivitis.
AB  - BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe form of allergic
      conjunctivitis, in which inflammatory infiltrates of the conjunctiva are
      characterized by CD3+ and CD30+ cells. Until today, the functional involvement of
      CD30+ T cells in VKC was unclear. Our aim was to evaluate the functional
      characteristics of CD30+ T cells after allergen stimulation in peripheral blood
      mononuclear cells obtained from patients with VKC. METHODS: Seventeen consecutive
      patients at the Institute of Ophthalmology with active forms of VKC were
      included. RESULTS: After allergen stimulation, we observed the frequency of CD30+
      T cells increased compared with non-stimulated cells (p<0.0001). The CD30+ T
      cells responded to the specific allergen-inducing expression of intracellular
      interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) compared with the
      CD30- T cells (p<0.0001). Increased early secretion of soluble CD30 was observed
      in the supernatant of the cultured cells from patients with keratoconjunctivitis,
      compared with healthy controls (p=0.03). Blockage with IL-4 significantly
      diminished CD30 frequency in the allergen-stimulated cells. CONCLUSIONS: Our
      results suggest that after allergenic stimulation, CD4+CD30+ cells are the most
      important source of IL-4, IL-5, and IFN-gamma. IL-4 acts as an activation loop
      that increases CD30 expression on T cells after specific stimulation. These
      findings suggest that CD4+CD30+ T cells are effector cells and play a significant
      role in the immune pathogenic response in patients with vernal
      keratoconjunctivitis.

PMID- 25999673
TI  - Label-free LC-MS/MS quantitative analysis of aqueous humor from keratoconic and
      normal eyes.
AB  - PURPOSE: The etiology of keratoconus (KC) and the factors governing its
      progression are not well understood. It has been suggested that this disease
      might be caused by biochemical alterations in the cornea; changes in the
      expression profiles of human aqueous humor (hAH) proteins have been observed in
      some diseases. To gain a new insight into the molecular mechanisms of KC
      pathology, we examined the hAH proteomes of those in the advanced stages of this
      disease. We used a high-throughput mass spectrometry approach to compare hAH
      protein expression in patients with KC and in control subjects. METHODS: Aqueous
      humor samples were acquired from five keratoconus patients during keratoplasty
      surgery and from five myopic control subjects during phakic intraocular lens
      implantation. Quantitative mass spectrometry analysis using spectral counting was
      performed to determine the relative amounts of hAH proteins in the samples from
      KC patients and control individuals. RESULTS: All KC patients included in the
      study presented severe keratoconus (K2 >52 D), and slit-lamp examination revealed
      microfolds in Descemet's membrane, without clinical signs of hydrops. We found
      significant differences between the expression levels of 16 proteins in the two
      groups. In KC samples, seven proteins were overexpressed and nine were
      underexpressed in comparison with the control group. Gene ontology analysis
      revealed that these deregulated proteins are implicated in several biologic
      processes, such as the regulation of proteolysis, responses to hypoxia, and
      responses to hydrogen peroxide, among others. CONCLUSIONS: The protein expression
      profiles in hAH from KC patients and myopic control subjects differ
      significantly. This result suggests that some components of the hAH proteome are
      involved in this disease. Further in-depth analysis of the hAH proteome should
      provide a better understanding of the mechanisms governing the pathophysiology of
      KC.

PMID- 25999675
TI  - Mutation analysis in 129 genes associated with other forms of retinal dystrophy
      in 157 families with retinitis pigmentosa based on exome sequencing.
AB  - PURPOSE: Mutations in 60 known genes were previously identified by exome
      sequencing in 79 of 157 families with retinitis pigmentosa (RP). This study
      analyzed variants in 129 genes associated with other forms of hereditary retinal
      dystrophy in the same cohort. METHODS: Apart from the 73 genes previously
      analyzed, a further 129 genes responsible for other forms of hereditary retinal
      dystrophy were selected based on RetNet. Variants in the 129 genes determined by
      whole exome sequencing were selected and filtered by bioinformatics analysis.
      Candidate variants were confirmed by Sanger sequencing and validated by analysis
      of available family members and controls. RESULTS: A total of 90 candidate
      variants were present in the 129 genes. Sanger sequencing confirmed 83 of the 90
      variants. Analysis of family members and controls excluded 76 of these 83
      variants. The remaining seven variants were considered to be potential pathogenic
      mutations; these were c.899A>G, c.1814C>G, and c.2107C>T in BBS2; c.1073C>T and
      c.1669C>T in INPP5E; and c.3582C>G and c.5704-5C>G in CACNA1F. Six of these seven
      mutations were novel. The mutations were detected in five unrelated patients
      without a family history, including three patients with homozygous or compound
      heterozygous mutations in BBS2 and INPP5E, and two patients with hemizygous
      mutations in CACNA1F. None of the patients had mutations in the genes associated
      with autosome dominant retinal dystrophy. CONCLUSIONS: Only a small portion of
      patients with RP, about 3% (5/157), had causative mutations in the 129 genes
      associated with other forms of hereditary retinal dystrophy.

PMID- 25999674
TI  - The efficacy of microarray screening for autosomal recessive retinitis pigmentosa
      in routine clinical practice.
AB  - PURPOSE: To determine the efficacy of multiple versions of a commercially
      available arrayed primer extension (APEX) microarray chip for autosomal recessive
      retinitis pigmentosa (arRP). METHODS: We included 250 probands suspected of arRP
      who were genetically analyzed with the APEX microarray between January 2008 and
      November 2013. The mode of inheritance had to be autosomal recessive according to
      the pedigree (including isolated cases). If the microarray identified a
      heterozygous mutation, we performed Sanger sequencing of exons and exon-intron
      boundaries of that specific gene. The efficacy of this microarray chip with the
      additional Sanger sequencing approach was determined by the percentage of
      patients that received a molecular diagnosis. We also collected data from genetic
      tests other than the APEX analysis for arRP to provide a detailed description of
      the molecular diagnoses in our study cohort. RESULTS: The APEX microarray chip
      for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our
      cohort. Additional Sanger sequencing yielded a second mutation in 17 patients
      (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients
      (15.2%) received a molecular diagnosis after analysis using the microarray and
      additional Sanger sequencing approach. Further genetic analyses after a negative
      result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP
      (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia
      (n = 1). CONCLUSIONS: The efficacy of the commercially available APEX microarray
      chips for arRP appears to be low, most likely caused by the limitations of this
      technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up
      to 40% have been reported for next-generation sequencing (NGS) techniques that,
      as expected, thereby outperform targeted APEX analysis.

PMID- 25999676
TI  - Clinical presentations of X-linked retinoschisis in Taiwanese patients confirmed
      with genetic sequencing.
AB  - PURPOSE: To investigate the clinical characteristics of X-linked retinoschisis
      (XLRS) and identify genetic mutations in Taiwanese patients with XLRS. METHODS:
      This study included 23 affected males from 16 families with XLRS. Fundus
      photography, spectral domain optical coherent tomography (SD-OCT), fundus
      autofluorescence (FAF), and full-field electroretinograms (ERGs) were performed.
      The coding regions of the RS1 gene that encodes retinoschisin were sequenced.
      RESULTS: The median age at diagnosis was 18 years (range 4-58 years). The best
      corrected visual acuity ranged from no light perception to 20/25. The typical
      spoke-wheel pattern in the macula was present in 61% of the patients (14/23)
      while peripheral retinoschisis was present in 43% of the patients (10/23). Four
      eyes presented with vitreous hemorrhage, and two eyes presented with leukocoria
      that mimics Coats' disease. Macular schisis was identified with SD-OCT in 82% of
      the eyes (31/38) while foveal atrophy was present in 18% of the eyes (7/38).
      Concentric area of high intensity was the most common FAF abnormality observed.
      Seven out of 12 patients (58%) showed electronegative ERG findings. Sequencing of
      the RS1 gene identified nine mutations, six of which were novel. The mutations
      are all located in exons 4-6, including six missense mutations, two nonsense
      mutations, and one deletion-caused frameshift mutation. CONCLUSIONS: XLRS is a
      clinically heterogeneous disease with profound phenotypic inter- and
      intrafamiliar variability. Genetic sequencing is valuable as it allows a definite
      diagnosis of XLRS to be made without the classical clinical features and ERG
      findings. This study showed the variety of clinical features of XLRS and reported
      novel mutations.

PMID- 25999678
TI  - Optical coherence tomography enables imaging of tumor initiation in the TAg-RB
      mouse model of retinoblastoma.
AB  - PURPOSE: Retinoblastoma is the most common primary intraocular malignancy in
      children. Although significant advances in treatment have decreased mortality in
      recent years, morbidity continues to be associated with these therapies, and
      therefore, there is a pressing need for new therapeutic options. Transgenic mouse
      models are popular for testing new therapeutics as well as studying the
      pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model
      has close molecular and histological resemblance to human retinoblastoma tumors;
      these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T
      antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging
      could be used to document tumor growth in the TAg-RB model from the earliest
      stages of tumor development. METHODS: The Micron III rodent imaging system was
      used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice
      weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor
      development. Tumor morphology was confirmed with histological analysis. RESULTS:
      Before being visible on funduscopy, hyperreflective masses arising in the inner
      nuclear layer were evident at 2 weeks of age with OCT imaging. After most of
      these hyperreflective cell clusters disappeared around 4 weeks of age, the first
      tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into
      discrete, discoid tumors, preferentially in the periphery, that developed more
      irregular morphology over time, eventually merging and displacing the inner
      retinal layers into the vitreous. CONCLUSIONS: OCT is a non-invasive imaging
      modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we
      characterized TAg-positive cells as early as 2 weeks, corresponding to the
      earliest stages at which tumors are histologically evident, and well before they
      are evident with funduscopy. Tracking tumor growth from its earliest stages will
      allow better analysis of the efficacy of novel therapeutics and genetic factors
      tested in this powerful mouse model.

PMID- 25999677
TI  - Effect of HDAC Inhibitors on Corneal Keratocyte Mechanical Phenotypes in 3-D
      Collagen Matrices.
AB  - PURPOSE: Histone deacetylase inhibitors (HDAC) have been shown to inhibit the
      TGFbeta-induced myofibroblast transformation of corneal fibroblasts in 2-D
      culture. However, the effect of HDAC inhibitors on keratocyte spreading,
      contraction, and matrix remodeling in 3-D culture has not been directly assessed.
      The goal of this study was to investigate the effects of the HDAC inhibitors
      Trichostatin A (TSA) and Vorinostat (SAHA) on corneal keratocyte mechanical
      phenotypes in 3-D culture using defined serum-free culture conditions. METHODS:
      Rabbit corneal keratocytes were plated within standard rat tail type I collagen
      matrices (2.5 mg/ml) or compressed collagen matrices (~100 mg/ml) and cultured
      for up to 4 days in serum-free media, PDGF BB, TGFbeta1, and either 50 nM TSA, 10
      MUM SAHA, or vehicle (DMSO). F-actin, alpha-SM-actin, and collagen fibrils were
      imaged using confocal microscopy. Cell morphology and global matrix contraction
      were quantified digitally. The expression of alpha-SM-actin was assessed using
      western blotting. RESULTS: Corneal keratocytes in 3-D matrices had a quiescent
      mechanical phenotype, as indicated by a dendritic morphology, a lack of stress
      fibers, and minimal cell-induced matrix remodeling. This phenotype was generally
      maintained following the addition of TSA or SAHA. TGFbeta1 induced a contractile
      phenotype, as indicated by a loss of dendritic cell processes, the development of
      stress fibers, and significant matrix compaction. In contrast, cells cultured in
      TGFbeta1 plus TSA or SAHA remained dendritic and did not form stress fibers or
      induce ECM compaction. Western blotting showed that the expression of alpha-SM
      actin after treatment with TGFbeta1 was inhibited by TSA and SAHA. PDGF BB
      stimulated the elongation of keratocytes and the extension of dendritic processes
      within 3-D matrices without inducing stress fiber formation or collagen
      reorganization. This spreading response was maintained in the presence of TSA or
      SAHA. CONCLUSIONS: Overall, HDAC inhibitors appear to mitigate the effects of
      TGFbeta1 on the transformation of corneal keratocytes to a contractile,
      myofibroblast phenotype in both compliant and rigid 3-D matrices while preserving
      normal cell spreading and their ability to respond to the pro-migratory growth
      factor PDGF.

PMID- 25999679
TI  - Protein tyrosine phosphatase 1B regulates the activity of retinal pigment
      epithelial cells.
AB  - PURPOSE: To determine whether protein tyrosine phosphatase 1B (PTP1B) is
      expressed in rat retinal pigment epithelium (RPE) cells, to evaluate whether
      inhibition of PTP1B contributes to initiation of RPE cells into an active state,
      and to investigate the signaling pathways involved in this process. METHODS: Rat
      retinas were detached by trans-scleral injection of 1.4% sodium hyaluronate into
      the subretinal space. Immunocytochemistry evaluated the expression of PTP1B in
      RPE cells located at normal and detached retinas. From the cultured RPE cells
      treated with TCS-401, cell proliferation was assessed using a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetracolium bromide assay, and the protein
      expression levels of cyclin A and cyclin D1 were determined. The effect of TCS
      401 on cell differentiation was confirmed by immunostaining for alpha-smooth
      muscle actin and by western blot. Cell migration activity and PTP1B signaling
      mechanism were determined. Migration Assay was used to evaluate cell migration
      activity. PTP1B signaling mechanism was determined by use of PD98059 and
      LY294002. RESULTS: PTP1B was expressed in the RPE layer of the normal retina.
      After retinal detachment, weak immunolabeling of PTP1B was seen in the RPE cells.
      TCS-401 promoted the proliferation and expression of cyclin A and cyclin D1 in
      RPE cells. TCS-401 induced RPE cells to differentiate toward better contractility
      and motility. A migration assay proved that inhibiting PTP1B improved the
      migratory activity of RPE cells. TCS-401 activated extracellular signal-regulated
      kinase (Erk) and protein kinase B (Akt) phosphorylation. Pretreatment with
      PD98059 and LY294002 abolished TCS-401-induced activation of Erk, Akt, cell
      proliferation, and cell migration. CONCLUSIONS: PTP1B may be involved in
      regulating the active state of RPE cells. The inhibition of PTP1B promoted the
      proliferation, myofibroblast differentiation, and migration of RPE cells, and
      MEK/Erk and PI3K/Akt signaling pathways played important roles in the
      proliferation and migration process.

PMID- 25999680
TI  - Inactivation of acyclovir-sensitive and -resistant strains of herpes simplex
      virus type 1 in vitro by photodynamic antimicrobial chemotherapy.
AB  - PURPOSE: To evaluate the efficacy of photodynamic antimicrobial chemotherapy
      (PACT) with the new porphyrin derivative TONS 504 and a light-emitting diode
      (LED) against acyclovir (ACV)-sensitive and -resistant herpes simplex virus type
      1 (HSV-1). METHODS: Human FL cells infected with the viral strains were subjected
      to PACT with TONS 504 at various concentrations (0.01 to 10 mg/l) and irradiation
      at various light energies (10 to 30 J/cm(2)) and were then incubated for 24 h
      before analysis. RESULTS: Immunocytofluorescence analysis with antibodies to HSV
      1 revealed that PACT eliminated HSV-1 and ACV-resistant HSV-1 in a manner
      dependent on the TONS 504 concentration and light energy. Complete eradication of
      both viruses was apparent at a TONS 504 concentration of 10 mg/l and light energy
      of 10 to 30 J/cm(2) as well as at a TONS 504 concentration of 1 mg/l and light
      energy of 20 or 30 J/cm(2). No antiviral effect was apparent with TONS 504 in the
      absence of irradiation or with irradiation in the absence of TONS 504. Staining
      of cell nuclei with 4', 6-diamidino-2-phenylindole revealed no apparent
      cytotoxicity of the PACT system, a finding that was confirmed by the system's
      failure to induce the release of lactate dehydrogenase from the host cells.
      CONCLUSIONS: We conclude that our PACT system based on TONS 504 and an LED is
      effective for eliminating HSV-1 and ACV-resistant HSV-1 without a harmful effect
      on host cells.

PMID- 25999681
TI  - Third harmonic generation microscopy of a mouse retina.
AB  - PURPOSE: To demonstrate lipid-specific imaging of the retina through the use of
      third harmonic generation (THG), a multiphoton microscopic technique in which
      tissue contrast is generated from optical inhomogeneities. METHODS: A custom
      fiber laser and multiphoton microscope was constructed and optimized for
      simultaneous two-photon autofluorescence (TPAF) and THG retinal imaging. Imaging
      was performed using fixed-frozen sections of mouse eyes without the use of
      exogenous fluorescent dyes. In parallel experiments, a fluorescent nuclear stain
      was used to verify the location of the retinal cell nuclei. RESULTS: Simultaneous
      THG and TPAF images revealed all retinal layers with subcellular resolution. In
      BALB/c strains, the THG signal stems from the lipidic organelles of the cellular
      and nuclear membranes. In the C57BL/6 strain, the THG signal from the RPE cells
      originates from the pigmented granules. CONCLUSIONS: THG microscopy can be used
      to image structures of the mouse retina using contrast inherent to the tissue and
      without the use of a fluorescent dye or exogenously expressed recombinant
      protein.

PMID- 25999683
TI  - Is SPECT or CT Based Attenuation Correction More Quantitatively Accurate for
      Dedicated Breast SPECT Acquired with Non-Traditional Trajectories?
AB  - Attenuation correction is necessary for SPECT quantification. There are a variety
      of methods to create attenuation maps. For dedicated breast SPECT imaging, it is
      unclear if either SPECT- or CT-based attenuation map would provide the most
      accurate quantification and whether or not segmenting the different tissue types
      will have an effect on the qunatification. For these experiments, 99mTc diluted
      in methanol and water was filled into geometric and anthropomorphic breast
      phantoms and was imaged with a dedicated dual-modality SPECT-CT scanner. SPECT
      images were collected using a compact CZT camera with various 3D acquisitions
      including vertical and 30 degrees  tilted parallel beam, and complex sinusoidal
      trajectories. CT images were acquired using a quasi-monochromatic x-ray source
      and CsI(T1) flat panel digital detector in a half-cone beam geometry. Measured
      scatter correction for SPECT and CT were implemented. To compare photon
      attenuation correction in the reconstructed SPECT images, various volumetric
      attenuation matrices were derived from 1) uniform SPECT, 2) uniform CT, and 3)
      segmented CT, populated with different attenuation coefficient values.
      Comparisons between attenuation masks using phantoms consisting of materials with
      different attenuation values show that at 140 keV the differences in the
      attenuation between materials do not affect the quantification as much as the
      size and alignment of the attenuation map. The CT-based attenuation maps give
      quantitative values 30% below the actual value, but are consistent. While the
      SPECT-based attenuation maps can provide within 10% accurate quantitative values,
      but are less consistent.

PMID- 25999682
TI  - A metabolomic approach to dry eye disorders. The role of oral supplements with
      antioxidants and omega 3 fatty acids.
AB  - PURPOSE: We used nuclear magnetic resonance spectroscopy of hydrogen-1 nuclei
      ((1)H NMR S) to analyze the metabolic profile of reflex tears from patients with
      dry eye disorders. METHODS: We performed a prospective case-control study
      involving 90 participants: 55 patients diagnosed with dry eye syndrome (DESG) and
      35 healthy subjects (control group, CG). From the DESG, two subgroups were
      formed: mild DES (n=22) and moderate DES (n=33). Participants were prescribed an
      oral nutraceutic supplementation containing antioxidants and essential
      polyunsaturated fatty acids to be taken as three capsules per day for 3 months.
      Reflex tears (20-30 ul) were collected from the tear meniscus of both eyes of
      each subject with a microglass pipette. Nuclear magnetic resonance (NMR) spectra
      were acquired with a standard one-dimensional pulse sequence with water
      suppression; 256 free induction decays were collected into 64,000 data points
      with 14 ppm spectral width. RESULTS: Basal tears showed a differential
      metabolomic profile between groups. Almost 50 metabolites were identified by H
      cholesterol, N-acetylglucosamine, glutamate, amino-n-butyrate, choline, glucose,
      and formate were detected before supplementation and choline/acetylcholine after
      supplementation. The metabolic profile of the tears was statistically different
      between groups, as well as before and after supplementation. CONCLUSIONS: Our
      data indicate that DES induces changes in the tear metabolic profile that can be
      modified with appropriate oral supplementation with antioxidants and essential
      polyunsaturated fatty acids.

PMID- 25999684
TI  - Effect of alcaftadine 0.25% on ocular itch associated with seasonal or perennial
      allergic conjunctivitis: a pooled analysis of two multicenter randomized clinical
      trials.
AB  - PURPOSE: Seasonal and perennial allergic conjunctivitis represent the majority of
      cases of ocular allergy. This analysis was designed to evaluate the efficacy and
      safety of once-daily alcaftadine 0.25% in preventing ocular itching associated
      with seasonal or perennial allergic conjunctivitis. SUBJECTS AND METHODS: Pooled
      data from two double-masked, multicenter, placebo-controlled studies using the
      conjunctival allergen challenge (CAC) model of allergic conjunctivitis were
      analyzed. Subjects randomized to receive treatment with alcaftadine 0.25% or
      placebo were challenged with seasonal (grass, ragweed, trees) or perennial (cat
      dander, cat hair, dog dander, dust mites, cockroach) allergens, 16 hours after
      treatment instillation. The primary efficacy measure was subject-evaluated mean
      ocular itching at 3 minutes post-CAC. Secondary measures included ocular itching
      at 5 and 7 minutes post-CAC. The proportion of subjects with minimal itch (itch
      score <1) and zero itch (itch score =0), and safety were also assessed. RESULTS:
      A total of 189 subjects enrolled in the two studies were treated with alcaftadine
      or placebo. Overall, 129 subjects were challenged with seasonal allergens and 60
      subjects were challenged with perennial allergens. Alcaftadine 0.25% achieved a
      statistically significant reduction in mean itch score at 3, 5, and 7 minutes
      post-CAC compared with placebo in subjects challenged with seasonal allergens
      (P<0.0001 at all time points) and those challenged with perennial allergens
      (P<0.0001 at all time points). A higher percentage of subjects treated with
      alcaftadine compared with placebo achieved minimal itch (P<=0.001 versus placebo
      at all time points) and zero itch (P<0.05 at all time points except 7 minutes for
      perennial) when challenged with either seasonal or perennial allergens. No
      treatment-related or serious adverse events were reported. CONCLUSION: Once-daily
      alcaftadine 0.25% ophthalmic solution was well tolerated and demonstrated
      effective relief of ocular itching in subjects challenged with allergens classic
      for triggering either seasonal or perennial allergic conjunctivitis.

PMID- 25999685
TI  - Global reported endophthalmitis risk following intravitreal injections of anti
      VEGF: a literature review and analysis.
AB  - PURPOSE: To report on endophthalmitis occurrence and associated risk factors
      following the intravitreal injection of anti-VEGF agents based on a review of
      published literature. MATERIALS AND METHODS: A Medline search was performed using
      the terms "bevacizumab" and "ranibizumab". A total of 534 English-language
      articles of varying design and published from 2006 to November 2013 were analyzed
      for endophthalmitis occurrence and contributing perioperative factors. RESULTS: A
      total of 445,503 injections were counted. There were 103 cases of postinjection
      endophthalmitis in 176,124 injections (0.058%) with bevacizumab (Avastin) versus
      79 cases in 269,379 injections (0.029%) with ranibizumab (Lucentis). This
      difference was due to a significantly higher occurrence of culture-negative
      endophthalmitis associated with bevacizumab injections. Culture-positive risk was
      not statistically different between the two drugs. The reported use of
      postinjection topical antibiotics increased the risk of culture-positive
      endophthalmitis. No association was found with the use of povidone iodine, a lid
      speculum, a mask, or an operating room. Streptococcus spp. were the most
      prevalent causative organism, accounting for nine of 54 (17%) of all culture
      positive cases. CONCLUSION: Reported postinjection endophthalmitis occurred
      significantly more in patients treated with bevacizumab than those treated with
      ranibizumab. However, culture-positive occurrence was similar. Despite the
      potential for contamination at the time of drug compounding, bevacizumab does not
      appear to confer a higher risk of culture-positive endophthalmitis than
      ranibizumab. This study also suggests antibiotic use may increase endophthalmitis
      occurrence.

PMID- 25999686
TI  - Systematic review of the association between Alzheimer's disease and chronic
      glaucoma.

PMID- 25999687
TI  - Patient satisfaction with glaucoma therapy: reality or myth?
AB  - While safe and effective treatments for glaucoma exist, their effectiveness is
      compromised by poor compliance. Patients who have problems with their topical
      glaucoma medication are acknowledged to be at higher risk for poor compliance,
      frequent medication switching, and surgery. Patient satisfaction with therapy and
      its associated benefits have until recently taken second place to efficacy. The
      present study is a transverse cross-sectional epidemiological survey among
      glaucoma patients receiving therapy with prostaglandin analogs. The primary
      objective was to determine and characterize patient satisfaction with glaucoma
      therapy, and the secondary objective was to identify factors that may contribute
      to poor patient satisfaction. Ophthalmologists in the Netherlands included 199
      patients and 164 were analyzed. Patients were predominantly elderly with early,
      primary, open angle glaucoma. Eighty-nine percent of them stated they were
      satisfied or very satisfied with their treatment. However, signs of ocular
      surface disorder on ophthalmological examination were evident in 44% of patients,
      corneal fluorescein staining was positive in 28% of patients, and 38% of patients
      were using tear substitutes. The prevalence of blepharitis/meibomian gland
      dysfunction and dry eye was more than twice as high after the commencement of
      therapy compared with before therapy. Univariate analysis revealed that patient
      dissatisfaction with their glaucoma therapy was statistically significantly
      (P<0.001) associated with the presence of ocular surface disease, hyperemia,
      ocular signs, symptoms upon and between instillation, and the use of tear
      substitutes. Apparently, patients in the present study are satisfied with their
      treatment; 89% expressed satisfaction compared with only 11% who professed
      dissatisfaction. The results suggest that even if local adverse events and ocular
      surface disease, in particular, contribute to glaucoma patient dissatisfaction,
      only a minority of patients expressed such dissatisfaction. At the time of the
      study, most (94%) of the patients included were receiving preserved preparations.
      Further studies should evaluate the influence of preservative on patient
      satisfaction. 

PMID- 25999688
TI  - Indications and results in anophthalmic socket reconstruction using dermis-fat
      graft.
AB  - OBJECTIVES: To present the indications for a dermis-fat graft in anophthalmic
      socket reconstruction and evaluate the results of this procedure. DESIGN:
      Retrospective review, interventional case series. METHODS: In our study, there
      were 41 patients who received either primary or secondary dermis-fat graft
      between August 1, 2007 and July 31, 2012 at Songklanagarind Hospital. RESULTS:
      The type of dermis-fat graft used in our study consisted of both primary dermis
      fat grafts (6/41) and secondary dermis-fat grafts (35/41). The major indications
      for dermis-fat graft were exposure (13/41), extrusion (11/41), and volume
      insufficiency with a shallow fornix (10/41), which accounted for 82.9% of the
      total cases. A total of 30 patients were able to wear the eye prosthesis over a
      mean follow-up time of 32.3+/-19.0 months. The success rate of the dermis-fat
      graft alone was 73.3%, while that of the simultaneous dermis-fat graft and mucous
      membrane graft was 25%. CONCLUSION: The most common indications for a dermis-fat
      graft were extrusion and large exposure. Dermis-fat graft is an alternative
      implant type in complicated enucleation/evisceration patients, which has a good
      success rate.

PMID- 25999689
TI  - A novel intravitreal fluocinolone acetonide implant (Iluvien((r))) in the
      treatment of patients with chronic diabetic macular edema that is insufficiently
      responsive to other medical treatment options: a case series.
AB  - BACKGROUND: Iluvien((r)) is a novel, nonbiodegradable, sustained-release drug
      delivery system (0.2 MUg/d fluocinolone acetonide [FAc]) indicated in Europe for
      the treatment of vision impairment associated with chronic diabetic macular edema
      (DME), considered insufficiently responsive to available therapies. OBJECTIVE: To
      evaluate the safety and efficacy of 190-MUg FAc implant in patients with chronic
      DME refractory to other medical treatment options in a clinical setting. METHODS:
      Retrospective registry data were collected by using standard case report forms
      (CRFs). Prior to intravitreal injection of the FAc implant, all patients were
      treated either with a vascular endothelial growth factor (VEGF) antagonist and/or
      a steroid (triamcinolone, dexamethasone implant). Patients were excluded from
      receiving FAc if they had a known history of elevated intraocular pressure (IOP)
      following corticosteroid therapy, glaucoma, ocular hypertension, or any
      contraindications cited in the summary of product characteristics. Best-corrected
      visual acuity (BCVA) was the main study parameter. Central fovea thickness (CFT)
      and IOP were measured concurrently. These parameters were recorded prior to and
      after the injection of the 190-MUg FAc implant (between 1 week and 9 months).
      Injections were performed between May 2013 and March 2014. RESULTS: Fifteen eyes
      from ten patients were treated. Thirteen eyes (nine patients) were pseudophakic,
      and seven eyes (five patients) were vitrectomized prior to receiving therapy.
      BCVA improved in eleven eyes (73.3%), remained unchanged in two eyes (13.3%), and
      decreased slightly in two eyes (13.3%) at the last follow-up visit versus
      baseline levels. IOP increased in two patients and was controlled using fixed
      combination of IOP-lowering eyedrops or sectorial cyclocryotherapy (n=1).
      CONCLUSION: The 190-MUg FAc implant was efficacious and showed a favorable
      benefit-to-risk profile in the patient population with chronic DME of this case
      series that were refractory to other therapies. The longer-term efficacy and
      safety in a real-life setting is still being assessed in this center. FAc may
      offer an important treatment option for patients with chronic DME refractory to
      other treatment options.

PMID- 25999690
TI  - An atypical presentation of sinus mucopyocele in a pediatric cystic fibrosis
      patient.
AB  - This case report details an association of chronic allergic conjunctivitis and
      respiratory tract colonization in a cystic fibrosis (CF) patient due to an
      ethmoidal mucocele infected with Escherichia coli. A 3-year-old CF patient
      presented for evaluation with complaints of chronic periocular erythema,
      conjunctival injection, and irritation for 2 years. He was treated for presumed
      allergic conjunctivitis with no improvement and continued to have overall
      worsening of symptoms on the right greater than the left eye in a waxing and
      waning pattern. On presentation to the Bascom Palmer Eye Institute, he was noted
      to have telecanthus and prominent erythema in the region of the medial canthus.
      Orbital imaging disclosed a mucocele in the right ethmoid sinus. The patient
      underwent functional endoscopic sinus surgery, with successful marsupialization
      of the ethmoidal mucocele, which was found on culture to be infected with E.
      coli. Post-operatively with continuous pulmonary care, the patient remains free
      of allergic conjunctivitis and E. coli colonization of the upper airway. This
      case highlights the importance of analyzing the adjacent sinus in patients with
      chronic, relapsing allergic conjunctivitis refractory to medical management,
      particularly in patients with underlying systemic diseases such as CF. 

PMID- 25999692
TI  - Detection of cytomegalovirus in an immunocompetent adult presenting with acute
      retinal necrosis due to varicella-zoster virus: a case report.
AB  - BACKGROUND: To report a case of simultaneous detection of cytomegalovirus (CMV)
      in acute retinal necrosis (ARN) due to varicella-zoster virus (VZV) in an
      immunocompetent adult. METHODS: A 65-year-old healthy woman presented with
      necrotizing retinitis. Vitreous, tears, saliva, and swabs of the auricular and
      forehead skin areas were collected and tested by polymerase chain reaction
      analysis at various time points during the treatment period. RESULTS: VZV and CMV
      DNA were detected in the vitreous, tears, saliva, and skin. CMV was present in
      fewer copies than VZV in the vitreous. The retinal lesion clinically improved
      rapidly only by acyclovir. According to the clinical findings and the clinical
      responses to acyclovir, CMV seems not to cause ARN in this case. CONCLUSION: VZV
      and CMV DNA were detected in the vitreous of a patient with VZV ARN. CMV
      reactivation appeared to be asymptomatic.

PMID- 25999691
TI  - Antibacterial efficacy of prophylactic besifloxacin 0.6% and moxifloxacin 0.5% in
      patients undergoing cataract surgery.
AB  - BACKGROUND: The purpose of this study was to investigate the ocular bacterial
      flora in patients scheduled to undergo cataract surgery and compare the
      antibacterial effects of besifloxacin ophthalmic suspension 0.6% and moxifloxacin
      ophthalmic solution 0.5% in these patients. METHODS: This was a prospective,
      randomized, laboratory-masked clinical trial. Patients received besifloxacin or
      moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract
      surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow
      eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and
      after treatment, on the day of surgery (Visit 2). Swabs were processed for
      bacterial colony counts (in terms of colony-forming units) and species
      identification. In vitro antibiotic susceptibilities of isolates were determined
      using Clinical and Laboratory Standards Institute breakpoints. RESULTS: Fifty
      nine patients (n=28 besifloxacin, n=31 moxifloxacin) completed the study. The
      majority (73%) of conjunctival samples were culture negative at baseline. The
      most frequent isolates were coagulase-negative staphylococci (CoNS, 89%),
      specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the
      lid CFU values when administered QID for 3 days (P<=0.019), but only besifloxacin
      reduced the lid CFU estimate 1 hour following instillation of a single drop
      (P=0.039). Fewer besifloxacin-treated eyes had lids that were culture positive
      for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing
      regimen (P<=0.03). The minimum inhibitory concentration (MIC90) of besifloxacin
      against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that
      of moxifloxacin. CONCLUSION: Besifloxacin appeared more effective in reducing
      bacterial counts on eyelids of patients undergoing cataract surgery, with
      significant reductions as early as 1 hour postdose, compared with moxifloxacin.
      Besifloxacin was more active in vitro against MRSE.

PMID- 25999693
TI  - Preparation and characterization of genipin-cross-linked silk fibroin/chitosan
      sustained-release microspheres.
AB  - We report the effects of distinct concentrations of genipin and silk fibroin
      (SF):chitosan (CS) ratios on the formation of SF-CS composite microspheres. We
      selected microspheres featuring an SF:CS ratio of 1:1, encapsulated various
      concentrations of bovine serum albumin (BSA), and then compared their
      encapsulation efficiency and sustained-release rate with those of pure CS
      microspheres. We determined that the following five groups of microspheres were
      highly spherical and featured particle sizes ranging from 70 MUm to 147 MUm: mass
      ratio of CS:SF =1:0.5, 0.1 g or 0.5 g genipin; CS:SF =1:1, 0.05 g or 1 g genipin;
      and CS:SF =1:2, 0.5 g genipin. The microspheres prepared using 1:1 CS:SF ratio
      and 0.05 g genipin in the presence of 10 mg, 20 mg, and 50 mg of BSA exhibited
      encapsulation efficiencies of 50.16%+/-4.32%, 56.58%+/-3.58%, and 42.19%+/-7.47%,
      respectively. Fourier-transform infrared spectroscopy (FTIR) results showed that
      SF and CS were cross-linked and that the alpha-helices and random coils of SF
      were converted into beta-sheets. BSA did not chemically react with CS or SF.
      Moreover, thermal gravimetric analysis (TGA) results showed that the melting
      point of BSA did not change, which confirmed the FTIR results, and X-ray
      diffraction results showed that BSA was entrapped in microspheres in a
      noncrystalline form, which further verified the TGA and FTIR data. The sustained
      release microspheres prepared in the presence of 10 mg, 20 mg, and 50 mg of BSA
      burst release 30.79%+/-3.43%, 34.41%+/-4.46%, and 41.75%+/-0.96% of the entrapped
      BSA on the 1st day and cumulatively released 75.20%+/-2.52%, 79.16%+/-4.31%, and
      89.04%+/-4.68% in 21 days, respectively. The pure CS microspheres prepared in the
      presence of 10 mg of BSA burst release 39.53%+/-1.76% of BSA on the 1st day and
      cumulatively released 83.57%+/-2.33% of the total encapsulated BSA in 21 days.
      The SF-CS composite microspheres exhibited higher sustained release than did the
      pure CS microspheres, and thus these composite microspheres might function as a
      superior drug carrier. 

PMID- 25999694
TI  - A pharmacokinetic comparison of two voriconazole formulations and the effect of
      CYP2C19 polymorphism on their pharmacokinetic profiles.
AB  - PURPOSE: SYP-1018 is a lyophilized polymeric nanoparticle formulation of
      voriconazole that is under development for intravenous dosing. This study
      compared the pharmacokinetic and tolerability profiles of SYP-1018 with those of
      Vfend((r)), the marketed formulation of voriconazole. The effect of CYP2C19
      polymorphism on the voriconazole pharmacokinetics was also evaluated. METHODS: An
      open-label, two-treatment, two-period, two-sequence crossover study was conducted
      in 52 healthy male volunteers, who randomly received a single intravenous
      infusion of either of the two voriconazole formulations at 200 mg. Blood samples
      were collected up to 24 hours after drug administration for pharmacokinetic
      analysis. The plasma concentrations of voriconazole were determined using liquid
      chromatography with tandem mass spectrometry, and the pharmacokinetic parameters
      were estimated using a noncompartmental method. CYP2C19 genotype was identified
      in 51 subjects. RESULTS: The geometric mean ratio (90% confidence interval) of
      SYP-1018 to Vfend((r)) was 0.99 (0.93-1.04) for the maximum plasma concentrations
      (Cmax) and 0.97 (0.92-1.01) for the area under the concentration-time curve (AUC)
      from dosing to the last quantifiable concentration (AUClast). Nineteen homozygous
      extensive metabolizers (EMs, *1/*1), 19 intermediate metabolizers (IMs, *1/*2 or
      *1/*3), and ten poor metabolizers (PMs, *2/*2, *2/*3, or *3/*3) were identified,
      and the pharmacokinetic comparability between SYP-1018 and Vfend((r)) was also
      noted when analyzed separately by genotype. The systemic exposure to voriconazole
      was greatest in the PM group, followed by the IM, and then the EM groups.
      Furthermore, the intrasubject variability for Cmax and AUClast was greater in IMs
      and PMs than in EMs. No serious adverse event occurred, and both treatments were
      well tolerated. CONCLUSION: SYP-1018 had comparable pharmacokinetic and
      tolerability profiles to Vfend((r)) after a single intravenous infusion. CYP2C19
      genotype affected not only the pharmacokinetics of voriconazole, but its
      intrasubject variability. SYP-1018 can be further developed as a clinically
      effective alternative to Vfend((r)).

PMID- 25999695
TI  - Fixed-combination treatments for intraocular hypertension in Chinese patients -
      focus on bimatoprost-timolol.
AB  - Glaucoma is a common eye disease that can lead to irreversible vision loss if
      left untreated. The early diagnosis and treatment of primary open-angle glaucoma
      is challenging, and visual impairment in Chinese glaucoma patients is a serious
      concern. Most of these patients need more than one topical antiglaucoma agent to
      control their intraocular pressures (IOPs). In the People's Republic of China,
      the daily cost of different glaucoma medication varies greatly, and the treatment
      habits differ throughout the country. Prostaglandin analogs (PGAs) are
      recommended as first-line monotherapy, because of their efficacy and low risk of
      systemic side effects. Fixed-combination drops, particularly PGA-based fixed
      combinations, have recently been developed and used in patients with progression
      or who have failed to achieve their target IOPs. Here, we reviewed the current
      literature on the use of bimatoprost-timolol fixed combination (BTFC) in the
      People's Republic of China. BTFC has achieved good efficacy and tolerability in
      Chinese clinical trials. In addition, BTFC is more cost effective compared with
      other fixed combinations available in the People's Republic of China. Fixed
      combination drops may offer benefits, such as keeping the ocular surface healthy,
      convenience of administration, and improvement in long-term adherence and quality
      of life. Therefore, BTFC has great potential for the treatment of Chinese
      glaucoma patients. However, the long-term efficacy of BTFC, comparisons of BTFC
      with other fixed-combination drugs, and treatment adherence and persistence with
      treatment in Chinese patients are unknown and will require further study. 

PMID- 25999696
TI  - Prevalence of the CYP2D6*10 (C100T), *4 (G1846A), and *14 (G1758A) alleles among
      Iranians of different ethnicities.
AB  - The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and
      activity, thereby affecting individual responses to pharmacological treatment.
      Here, we compared the prevalence of the CYP2D6*10, *4, and 14* alleles in an
      Iranian population of different ethnicities with those of other populations.
      Allele and genotype frequency distributions of CYP2D6*10 variants and predicted
      phenotypes including extensive metabolizers, intermediate metabolizers, and poor
      metabolizers were analysed in blood samples of 300 unrelated healthy individuals
      in an Iranian population using polymerase chain reaction (PCR)-restriction
      fragment length polymorphism, PCR-single-strand conformation polymorphism, and
      direct genomic DNA sequencing. The CYP2D6*4 (G1846A) and *14 (G1758A) allelic
      frequencies were not detected in different ethnicities, demonstrating the absence
      of a significant contribution of these alleles in Iranian populations. However,
      the T/T, C/T, and C/C genotype frequencies of the CYP2D6*10 allele were
      significantly different (P<0.01) in all Iranian ethnic groups. Additionally, the
      frequency of the homozygous T/T variant of the CYP2D6*10 allele was significantly
      high in the Lure (P<0.017) and low in the Kurd (P<0.002) ethnicities. The
      frequency of the T/T variant of the CYP2D6*10 allele in central Iran was the
      highest (P<0.001), while the south of Iran had the lowest frequency (P<0.001).
      The frequency of the C/T variant of the CYP2D6*10 allele was significantly a bit
      high (P<0.001) in females compare to males, while the frequencies of the T/T
      variant in females is similar to males, which are 24.4% and 24.3%, respectively.
      In contrast to absence of the CYP2D6*4 (G1846A) and *14 (G1758A) alleles in
      Iranian populations of different ethnicities, the prediction of the CYP2D6*10
      allele is required in drug research and routine treatment, where the information
      would be helpful for clinicians to optimize therapy or identify persons at risk
      of adverse drug reactions before clinical trials. Approximately 39.3% of subjects
      (24.3% homozygous T/T CYP2D6*10 as poor metabolizers and 15% heterozygous C/T
      CYP2D6*10 as intermediate metabolizers) had this allele; therefore, the harmful
      effects of drugs are relatively common among Iranians. 

PMID- 25999698
TI  - Information and decision-making needs among people with affective disorders -
      results of an online survey.
AB  - BACKGROUND: Patient decision aids are one possibility for enabling and
      encouraging patients to participate in medical decisions. OBJECTIVE: This paper
      aims to describe patients' information and decision-making needs as a
      prerequisite for the development of high-quality, web-based patient decision aids
      for affective disorders. DESIGN: We conducted an online cross-sectional survey by
      using a self-administered questionnaire including items on Internet use, online
      health information needs, role in decision making, and important treatment
      decisions, performing descriptive and comparative statistical analyses.
      PARTICIPANTS: A total of 210 people with bipolar disorder/mania as well as 112
      people with unipolar depression participated in the survey. RESULTS: Both groups
      specified general information search as their most relevant information need and
      decisions on treatment setting (inpatient or outpatient) as well as decisions on
      pharmacological treatment as the most difficult treatment decisions. For
      participants with unipolar depression, decisions concerning psychotherapeutic
      treatment were also especially difficult. Most participants of both groups
      preferred shared decisions but experienced less shared decisions than desired.
      DISCUSSION AND CONCLUSION: Our results show the importance of information for
      patients with affective disorders, with a focus on pharmacological treatment and
      on the different treatment settings, and highlight patients' requirements to be
      involved in the decision-making process. Since our sample reported a chronic
      course of disease, we do not know if our results are applicable for newly
      diagnosed patients. Further studies should consider how the reported needs could
      be addressed in health care practice.

PMID- 25999697
TI  - A study on the hemocompatibility of dendronized chitosan derivatives in red blood
      cells.
AB  - Dendrimers are hyperbranched macromolecules with well-defined topological
      structures and multivalent functionalization sites, but they may cause
      cytotoxicity due to the presence of cationic charge. Recently, we have introduced
      alkyne-terminated poly(amidoamine) (PAMAM) dendrons of different generations
      (G=2,3) into chitosan to obtain dendronized chitosan derivatives [Cs-g-PAMAM
      (G=2,3)], which exhibited a better water solubility and enhanced plasmid DNA
      transfection efficiency. In this study, we attempted to examine the impact of Cs
      g-PAMAM (G=2,3) at different concentrations (25 MUg/mL, 50 MUg/mL, and 100
      MUg/mL) on the morphology, surface structure, and viability of rat red blood
      cells (RBCs). The results showed that treatment of RBCs with Cs-g-PAMAM (G=2,3)
      at 50 MUg/mL and 100 MUg/mL induced a slightly higher hemolysis than Cs, and Cs-g
      PAMAM (G=3) caused a slightly higher hemolysis than Cs-g-PAMAM (G=2), but all
      values were <5.0%. Optical microscopic and atomic force microscopic examinations
      indicated that Cs-g-PAMAM (G=2,3) caused slight RBC aggregation and lysis.
      Treatment of RBCs with 100 MUg/mL Cs-g-PAMAM (G=3) induced echinocytic
      transformation, and RBCs displayed characteristic irregular contour due to the
      folding of the periphery. Drephanocyte-like RBCs were observed when treated with
      100 MUg/mL Cs-g-PAMAM (G=3). Erythrocytes underwent similar shape transition upon
      treatment with Cs-g-PAMAM (G=2) or Cs. The roughness values (Rms) of RBCs
      incubated with Cs-g-PAMAM (G=2,3) were significantly larger than those for RBCs
      incubated with physiological saline (P<0.01), but the Rms showed no difference
      for Cs and Cs-g-PAMAM (G=2,3) (P>0.05). Furthermore, Cs-g-PAMAM (G=2,3) exhibited
      a lower cytotoxicity in human kidney 293T cells. These results indicate that Cs-g
      PAMAM (G=2,3) are hemocompatible but may disturb membrane and lipid structures at
      higher concentrations. Further safety and biocompatibility evaluations are
      warranted for Cs-g-PAMAM. Our findings prove helpful for a better understanding
      of the advantages of combining PAMAM dendrimers and chitosan to design and
      develop new, safe, and effective drug delivery vehicles. 

PMID- 25999699
TI  - Determinants of medication adherence among adults with type 2 diabetes mellitus
      in three Malaysian public health clinics: a cross-sectional study.
AB  - Medication adherence (MA) in adults with type 2 diabetes mellitus (T2D) is
      associated with improved disease control (glycated hemoglobin, blood pressure,
      and lipid profile), lower rates of death and diabetes-related complications,
      increased quality of life, and decreased health care resource utilization.
      However, there is a paucity of data on the effect of diabetes-related distress,
      depression, and health-related quality of life on MA. This study examined factors
      associated with MA in adults with T2D at the primary care level. This was a cross
      sectional study conducted in three Malaysian public health clinics, where adults
      with T2D were recruited consecutively in 2013. We used the 8-item Morisky
      Medication Adherence Scale (MMAS-8) to assess MA as the main dependent variable.
      In addition to sociodemographic data, we included diabetes-related distress,
      depressive symptoms, and health-related quality of life as independent variables.
      Independent association between the MMAS-8 score and its determinants was done
      using generalized linear models with a gamma distribution and log link function.
      The participant response rate was 93.1% (700/752). The majority were female
      (52.8%), Malay (52.9%), and married (79.1%). About 43% of patients were
      classified as showing low MA (MMAS-8 score <6). Higher income (adjusted odds
      ratio 0.90) and depressive symptoms (adjusted odds ratio 0.99) were significant
      independent determinants of medication non-adherence in young adults with T2D.
      Low MA in adults with T2D is a prevalent problem. Thus, primary health care
      providers in public health clinics should focus on MA counselling for adult T2D
      patients who are younger, have a higher income, and symptoms of depression. 

PMID- 25999700
TI  - Behavioral economics survey of patients with type 1 and type 2 diabetes.
AB  - BACKGROUND: Adherence to treatment and the metabolic control of diabetes are
      challenging in many patients with diabetes. The theory of neuroeconomics can
      provide important clues for understanding unreasonable human behavior concerning
      decisions between outcomes occurring at different time points. OBJECTIVE: We
      investigated patients with type 1 and type 2 diabetes to determine whether
      patients who are at a risk of developing complications are less risk averse. We
      also examined whether patients with type 1 and type 2 diabetes have different
      behavioral traits in decision making under risk. METHODS: We conducted a
      behavioral economics survey of 219 outpatients, 66 with type 1 diabetes and 153
      with type 2 diabetes. All patients had been referred by general practitioners or
      other departments in the hospital. At the time of the survey, levels of
      hemoglobin A1c were not significantly different between patients with type 1 and
      type 2 diabetes. RESULTS: Patients with type 2 diabetes showed a lower response
      rate to the survey compared with patients with type 1 diabetes (71.9% vs 87.9%,
      P<0.01). Logistic regression analysis indicated that diabetic retinopathy was
      negatively associated with risk averse in pricing of hypothetical lotteries,
      myopic time preference, willingness to pay for preventive medicine, and levels of
      satisfaction with life. Diabetic nephropathy was also negatively associated with
      risk averse in pricing of hypothetical lotteries. Detailed analysis revealed that
      a lower proportion of patients with type 2 diabetes (22.7%) were categorized as
      risk averse compared with patients with type 1 diabetes (43.1%, P<0.05) in
      hypothetical lottery risk estimation. CONCLUSION: This is the first report that
      investigated patients with diabetes in a clinical setting using a method based on
      behavioral economics. The results suggest that the attitude of patients toward
      risk plays an important role in the progress of the complications of diabetes.
      Different educational and psychological approaches may be necessary to assess
      patients with diabetes based on whether they have traits such as risk seeking or
      risk averse.

PMID- 25999701
TI  - Patient satisfaction with radioiodine treatment and telephone follow-up for the
      management of thyrotoxicosis.
AB  - BACKGROUND AND OBJECTIVE: Patient satisfaction is of paramount importance when
      delivering a patient-centered service. Our hospital has been a center for the use
      of radioiodine to treat thyrotoxicosis for several years, but we began carrying
      out patient satisfaction surveys and implementing changes after 2008. The aim of
      the project reported here was to assess patient satisfaction with our radioiodine
      treatment and telephone follow-up service, and to compare results with our
      previous surveys. PATIENTS AND METHODS: Anonymous patient satisfaction
      questionnaires were sent to all patients who received radioiodine treatment for
      thyrotoxicosis between January 2012 and December 2013. Patients were asked to
      answer four questions concerning informed consenting, treatment, and telephone
      follow-up using a four-point Likert scale, and post back the questionnaires. A
      suggestion box was included for comments and suggestions for improvement.
      RESULTS: A total of 56 questionnaires were posted out (to 44 females and 12
      males) and 34 questionnaires were returned (60.8% response rate). Between 94% and
      100% of the responders, depending on the question asked, were satisfied with the
      service they received. Patients also put useful comments and suggestions in the
      suggestion box provided. CONCLUSION: Patients with thyrotoxicosis were satisfied
      with our radioiodine treatment and telephone follow-up service. This survey has
      revealed areas for service improvement, and highlights the importance of patient
      satisfaction when assessing a patient-centered service.

PMID- 25999702
TI  - Antibiotic and shared decision-making preferences among adolescents in Malaysia.
AB  - BACKGROUND: The purpose of this study was to establish baseline information on
      the current level of knowledge about, attitude toward, and experience with
      antibiotic usage, and preferences for shared decision making among adolescents in
      Malaysia. METHODS: A cross-sectional survey, involving 1,105 respondents who were
      aged between 13 and 17 years and who lived in Malaysia, was conducted using a
      validated questionnaire. The survey assessed knowledge, attitude, and experience
      with regard to antibiotic usage, and adolescents' preferences for the style of
      shared decision-making process. RESULTS: The majority (n=786 [71.13%]) of the
      respondents had a low level of knowledge, 296 (26.79%) had a moderate level of
      knowledge, and 23 (2.08%) had a high level of knowledge. Further, they
      demonstrated a slightly negative attitude mean score of 3.30+/-0.05 (range: 0-8
      points) but a positive experience mean score of 2.90+/-0.029 (range: 0-4 points).
      There was a positive correlation between knowledge and attitude scores, with a
      higher knowledge level associated with a more positive attitude toward antibiotic
      usage (r=0.257, P<0.001). Higher knowledge scores were associated with a more
      negative experience with antibiotic usage (r=-0.83, P=0.006). When assessing
      preference in shared decision making, more adolescents preferred an active role
      (n=408 [37%]) compared with collaborative (n=360 [32.6%]) or passive (n=337
      [30.5%]) (P=0.028) roles. CONCLUSION: Current health care settings should involve
      adolescents in the decision-making process. Education packages can be introduced
      to improve adolescents' knowledge of and practice of taking antibiotics, as well
      as to encourage their participation in decision making, in an attempt to reduce
      misuse of antibiotics.

PMID- 25999703
TI  - Response to "Oral health in the elderly patient and its impact on general well
      being: a nonsystematic review" paper.

PMID- 25999705
TI  - Pleural plaques in smoking-associated fibrosis and pulmonary asbestosis.

PMID- 25999704
TI  - Prevention and optimal management of sarcopenia: a review of combined exercise
      and nutrition interventions to improve muscle outcomes in older people.
AB  - The growing recognition of sarcopenia, the age-related loss of skeletal muscle
      mass and function, has highlighted the need to understand more about its
      etiology. Declines in muscle mass and strength are expected aspects of aging, but
      there is significant variability between individuals in rates of loss. Although
      some of these differences can be explained by fixed factors, such as sex, much of
      the remaining variation is unexplained. This has led to increasing interest in
      the influence of adult lifestyle, particularly in the effects of modifiable
      factors such as physical activity and diet, and in identifying intervention
      opportunities both to prevent and manage sarcopenia. A number of trials have
      examined the separate effects of increased exercise or dietary supplementation on
      muscle mass and physical performance of older adults, but less is known about the
      extent to which benefits of exercise training could be enhanced when these
      interventions are combined. In a comprehensive review of the literature, we
      consider 17 studies of older adults (>=65 years) in which combined nutrition and
      exercise interventions were used to increase muscle strength and/or mass, and
      achieve improvements in physical performance. The studies were diverse in terms
      of the participants included (nutritional status, degree of physical frailty),
      supplementation strategies (differences in nutrients, doses), exercise training
      (type, frequency), as well as design (duration, setting). The main message is
      that enhanced benefits of exercise training, when combined with dietary
      supplementation, have been shown in some trials - indicating potential for future
      interventions, but that existing evidence is inconsistent. Further studies are
      needed, particularly of exercise training combined with dietary strategies that
      increase intakes of a range of nutrients, as well as bioactive non-nutrients, to
      provide the evidence on which public health and clinical recommendations can be
      based. 

PMID- 25999706
TI  - Lower 30-day readmission rates with roflumilast treatment among patients
      hospitalized for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Few data exist related to the impact of roflumilast on health care
      utilization. This retrospective study estimated 30-day hospital readmission rates
      between patients who did and did not use roflumilast among those with COPD
      hospitalizations. METHODS: Data were from MarketScan, a large US commercial
      health insurance claims database. Patients aged >=40 years with at least one
      hospitalization for COPD between 2010 and 2011 were included. The roflumilast
      group included patients who used roflumilast within 14 days after the first
      hospitalization (index), while the comparison group (non-roflumilast) included
      patients who did not use roflumilast during the study period. Continuous
      enrollment for at least 6 months before and 30 days after the index date was
      required. The 30-day hospitalization rate was calculated after the index
      hospitalization. Conditional logistic regression with propensity score 1:3
      matching was employed to assess the difference in 30-day hospital readmission
      rates between the roflumilast and non-roflumilast groups, adjusting for baseline
      characteristics, comorbidity, health care utilization, and COPD medication use
      within 14 days after the index date. RESULTS: A total of 15,755 COPD patients met
      the selection criteria, ie, 366 (2.3%) in the roflumilast group and 15,389
      (97.7%) in the non-roflumilast group. The mean (+/- standard deviation) age was
      71+/-12.5 years and 52% were female. After propensity score matching, all-cause
      30-day hospitalization rates were 6.9% and 11.1% in the roflumilast and non
      roflumilast groups, respectively. COPD-related 30-day hospitalization rates were
      6.3% and 9.2% in the roflumilast and non-roflumilast groups, respectively.
      Conditional logistic regression identified a significantly lower likelihood of
      all-cause 30-day readmission (odds ratio 0.59, 95% confidence interval 0.37-0.93,
      P=0.023) for roflumilast patients relative to non-roflumilast patients.
      CONCLUSION: This study showed, in a real-world setting, that use of roflumilast
      was associated with a lower rate of hospital readmission within 30 days among
      patients hospitalized for COPD.

PMID- 25999707
TI  - Effect of N-acetylcysteine in COPD patients with different microsomal epoxide
      hydrolase genotypes.
AB  - BACKGROUND: The role of the antioxidant N-acetylcysteine (NAC) in the treatment
      of chronic obstructive pulmonary disease (COPD) has not been clarified as yet. In
      early studies, we found that the proportion of smokers with COPD having extremely
      slow/slow microsomal epoxide hydrolase (EPHX1) enzyme activity is significantly
      higher than that in healthy smokers. The purpose of this study was to evaluate
      whether different EPHX1 enzyme activity is related to differential therapeutic
      effects of treatment with NAC in COPD. METHODS: A total of 219 patients with COPD
      were randomly allocated to an extremely slow/slow EPHX1 enzyme activity group
      (n=157) or a fast/normal EPHX1 enzyme activity group (n=62) according to their
      EPHX1 enzyme activity. Both groups were treated with NAC 600 mg twice daily for
      one year. The main study parameters, including forced expiratory volume in one
      second (FEV1), St George's Respiratory Questionnaire (SGRQ), and yearly
      exacerbation rate, were measured at baseline and at 6-month intervals for one
      year. RESULTS: Both FEV1 and SGRQ symptom scores were improved after treatment
      with NAC in the slow activity group when compared with the fast activity group.
      Further, changes in FEV1 and SGRQ symptom score in patients with mild-to-moderate
      COPD were more significant than those in patients with severe-to-very severe
      COPD. The yearly exacerbation rates were reduced in both groups, but the
      reduction in the slow activity group was significantly lower than in the fast
      activity group. CONCLUSION: NAC treatment in COPD patients with extremely
      slow/slow EPHX1 enzyme activity improves FEV1 and the SGRQ symptom score,
      especially in those with mild-to-moderate COPD, and polymorphism in the EPHX1
      gene may have a significant role in differential responses to treatment with NAC
      in patients with COPD.

PMID- 25999708
TI  - Epidemiology, severity, and treatment of chronic obstructive pulmonary disease in
      the United Kingdom by GOLD 2013.
AB  - OBJECTIVES: In 2013, the Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) updated the management strategy on COPD based on severity using a combined
      assessment of symptoms, degree of airflow limitation, and number of
      exacerbations. This study quantified prevalence and incidence of COPD in the
      United Kingdom and estimated disease severity by GOLD 2013 categories A/B (low
      risk) and C/D (high risk). METHODS: The Clinical Practice Research Datalink was
      used to identify COPD patients >=40 years. Patient characteristics were
      described, and prevalence was calculated on December 31, 2013. Five-year
      incidence (2009-2013) was estimated, with rates standardized using 2011 UK
      population age and sex. To classify patients by GOLD categories, spirometry
      results, the modified British Medical Research Council grade, and history of
      exacerbations were used. RESULTS: The prevalent cohort comprised 49,286 patients
      with COPD with mean age 70 years; 51.0% were male. Overall prevalence was 33.3
      per 1,000 persons (95% confidence interval [CI]: 33.1-33.6); 66.4% were
      classified as GOLD A/B and 33.6% as C/D. The standardized prevalence of GOLD A/B
      was 21.9 per 1,000 persons (95% CI: 21.7-22.1) and of C/D was 11.1 (95% CI: 10.9
      11.2). A total of 27,224 newly diagnosed COPD patients were identified with mean
      age 67 years at diagnosis; 53.0% were male. Incidence was 2.2 per 1,000 person
      years (95% CI: 2.2-2.3); 68.7% were classified in categories A/B and 31.3% in
      C/D, of which 17.2% did not receive COPD maintenance medication. CONCLUSION: A
      third of COPD patients in the UK are considered high risk (GOLD 2013 categories
      C/D), and a third of patients are diagnosed for the first time at these severe
      stages. Given the progressive nature of the disease, results suggest that closer
      attention to respiratory symptoms for early detection, diagnosis, and appropriate
      treatment of COPD in the UK is warranted.

PMID- 25999709
TI  - Expiratory flow limitation relates to symptoms during COPD exacerbations
      requiring hospital admission.
AB  - BACKGROUND: Expiratory flow limitation (EFL) is seen in some patients presenting
      with a COPD exacerbation; however, it is unclear how EFL relates to the clinical
      features of the exacerbation. We hypothesized that EFL when present contributes
      to symptoms and duration of recovery during a COPD exacerbation. Our aim was to
      compare changes in EFL with symptoms in subjects with and without flow-limited
      breathing admitted for a COPD exacerbation. SUBJECTS AND METHODS: A total of 29
      subjects with COPD were recruited within 48 hours of admission to West China
      Hospital for an acute exacerbation. Daily measurements of post-bronchodilator
      spirometry, resistance, and reactance using the forced oscillation technique and
      symptom (Borg) scores until discharge were made. Flow-limited breathing was
      defined as the difference between inspiratory and expiratory respiratory system
      reactance (EFL index) greater than 2.8 cmH2O.s.L(-1). The physiological
      predictors of symptoms during recovery were determined by mixed-effect analysis.
      RESULTS: Nine subjects (31%) had flow-limited breathing on admission despite
      similar spirometry compared to subjects without flow-limited breathing.
      Spirometry and resistance measures did not change between enrolment and
      discharge. EFL index values improved in subjects with flow-limited breathing on
      admission, with resolution in four patients. In subjects with flow-limited
      breathing on admission, symptoms were related to inspiratory resistance and EFL
      index values. In subjects without flow-limited breathing, symptoms related to
      forced expiratory volume in 1 second/forced vital capacity. In the whole cohort,
      EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03).
      CONCLUSION: The presence of flow-limited breathing as well as abnormal
      respiratory system mechanics contribute independently to symptoms during COPD
      exacerbations.

PMID- 25999710
TI  - Effective small interfering RNA delivery in vitro via a new stearylated cationic
      peptide.
AB  - A crucial bottleneck in RNA interference-based gene therapy is the lack of safe
      and efficient delivery systems. Here, a novel small interfering RNA (siRNA)
      delivery peptide, STR-HK, was constructed by conjugating a stearyl end to the N
      terminus of the peptide sequence HHHPKPKRKV, where PKPKRKV is an altered sequence
      of the nucleus localization signal (PKKKRKV) and contributes to the cytosol
      localization of STR-HK-siRNA complexes. Histidine is a linker and plays an
      important role in disrupting the endosomal membrane via the proton sponge effect.
      As expected, STR-HK formed complexes with siRNA with a particle size of 80-160 nm
      in diameter and efficiently delivered Cy3-labeled glyceraldehyde 3-phosphate
      dehydrogenase siRNA into PC-3 human prostate cancer cells. The transfection
      efficiency of STR-HK at molar ratio of 60/1 was comparable to that of
      Lipofectamine 2000, one of the most efficient commercially available transfection
      reagents. Furthermore, the STR-HK-siRNA complexes exhibited minimal cytotoxicity,
      which was significantly lower than that of Lipofectamine. Taken together, the
      strategy of conjugating the stearyl moiety with HHHPKPKRKV as a non-viral siRNA
      delivery system is advantageous. 

PMID- 25999711
TI  - Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic
      peptide on bone loss in a murine bone resorption model.
AB  - We investigated the biological activity of W9, a bone resorption inhibitor
      peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl
      group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by
      pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male
      C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous
      injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day
      incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24
      mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that
      received a normal calcium diet with NanoClik nanoparticle injections without W9
      were used as a control group. Radiological analyses showed that administration of
      W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone
      mineral density in the long bones and lumbar vertebrae, but only when the
      NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the
      proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik
      nanoparticles prevented the increase in bone resorption indices induced by a low
      calcium diet, which was confirmed by measurement of serum bone resorption
      markers. These data suggest that NanoClik nanoparticles could be a useful carrier
      for peptide therapeutics, and also demonstrate that daily subcutaneous injections
      of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo.
      An osteoclastogenesis inhibition assay performed in vitro confirmed a slower
      release profile of W9 from NanoClik nanoparticles compared with conventional CHP
      nanogels. 

PMID- 25999712
TI  - Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal
      fibrosis in vivo.
AB  - Renal fibrosis is the final common pathway leading to end-stage renal disease.
      Although microRNA (miR) was recently shown to be involved in the development of
      renal fibrosis, few studies have focused on the effects on renal fibrosis of
      exogenous miR delivered in an in vivo therapeutic setting. The study reported
      here investigated the effects of miR-146a delivery using polyethylenimine
      nanoparticles (PEI-NPs) on renal fibrosis in vivo. PEI-NPs bearing miR-146 or
      control-miR (nitrogen/phosphate ratio: 6) were injected into the tail vein of a
      mouse model of renal fibrosis induced by unilateral ureteral obstruction. PEI-NPs
      bearing miR-146 significantly enhanced miR-146a expression in the obstructed
      kidney compared with the control group, while inhibiting the renal fibrosis area,
      expression of alpha-smooth muscle actin, and infiltration of F4/80-positive
      macrophages into the obstructed kidney. In addition, PEI-NPs bearing miR-146a
      inhibited the transforming growth factor beta 1-Smad and tumor necrosis factor
      receptor-associated factor 6-nuclear factor kappa B signaling pathways. Control
      miR-PEI-NPs did not show any of these effects. These results suggest that the
      delivery of miR-146a attenuated renal fibrosis by inhibiting pro-fibrotic and
      inflammatory signaling pathways and that the delivery of appropriate miRs may be
      a therapeutic option for preventing renal fibrosis in vivo. 

PMID- 25999713
TI  - pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for
      oral delivery of insulin.
AB  - This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide)
      (PLGA) nanoparticle composite microcapsules for oral delivery of insulin.
      Firstly, insulin-sodium oleate complex was prepared by the hydrophobic ion
      pairing method and then encapsulated into PLGA nanoparticles by the emulsion
      solvent diffusion method. In order to reduce the burst release of insulin from
      PLGA nanoparticles and deliver insulin to specific gastrointestinal regions,
      hence to enhance bioavailability of insulin, the PLGA nanoparticles were further
      encapsulated into Eudragit((r)) FS 30D to prepare PLGA nanoparticle composite
      microcapsules by organic spray-drying method. The preparation was evaluated in
      vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug
      release studies revealed that the drug release was pH dependent, and the in vivo
      results demonstrated that the formulation of PLGA nanoparticle composite
      microcapsules was an effective candidate for oral insulin delivery. 

PMID- 25999714
TI  - Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for
      enhancement of its anticancer effect.
AB  - PURPOSE: The normal metabolite methylglyoxal (MG) specifically kills cancer cells
      by inhibiting glycolysis and mitochondrial respiration without much adverse
      effect upon normal cells. Though the anticancer property of MG is well
      documented, its gradual enzymatic degradation in vivo has prompted interest in
      developing a nanoparticulate drug delivery system to protect it and also to
      enhance its efficacy. MATERIALS AND METHODS: MG-conjugated chitosan nanoparticles
      (Nano-MG) were prepared by conjugating the carbonyl group of MG with the amino
      group of chitosan polymer (Schiff's base formation). Nano-MG were characterized
      in detail using the dynamic light scattering method, zeta potential measurement,
      Fourier transform infrared spectroscopy, and transmission electron microscopic
      analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro
      release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites
      carcinoma (EAC) cells, human breast cancer cell line HBL-100, and lung epithelial
      adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with
      bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye
      exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3
      (4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis
      of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo
      studies were performed on both EAC cells inoculated and also in sarcoma-180
      induced solid tumor-bearing Swiss albino mice to assess the anticancer activity
      of Nano-MG in comparison to bare MG with varying doses, times, and administrative
      routes. RESULTS: Fourier transform infrared spectroscopy revealed the presence of
      imine groups in Nano-MG due to conjugation of the amino group of chitosan and
      carbonyl group of MG with diameters of nanoparticles ranging from 50-100 nm. The
      zeta potential of Nano-MG was +21 mV and they contained approximately 100 MUg of
      MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity
      and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare
      MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the
      concerned doses. Studies with EAC cells also showed increased cell death of
      nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo
      studies further demonstrated the efficacy of Nano-MG over bare MG and found them
      to be about 400 times more potent in EAC-bearing mice and nearly 80 times more
      effective in sarcoma-180-bearing mice. Administration of ascorbic acid and
      creatine during in vivo treatments augmented the anticancer effect of Nano-MG.
      CONCLUSION: The results clearly indicate that Nano-MG may constitute a promising
      tool in anticancer therapeutics in the near future.

PMID- 25999715
TI  - Functionalized self-assembling peptide improves INS-1 beta-cell function and
      proliferation via the integrin/FAK/ERK/cyclin pathway.
AB  - Islet transplantation is considered to be a curative treatment for type 1
      diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to
      beta-cell destruction and graft dysfunction. In this study, we developed a
      functionalized self-assembling peptide, KLD-F, with ECM mimic motifs derived from
      fibronectin and collagen IV, and evaluated its effect on beta-cell function and
      proliferation. Atomic force microscopy and rheological results showed that KLD-F
      could self-assemble into a nanofibrous scaffold and change into a hydrogel in
      physiological saline condition. In a three-dimensional cell culture model, KLD-F
      improved ECM remodeling and cell-cell adhesion of INS-1 beta-cells by
      upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced
      glucose-stimulated insulin secretion and expression of beta-cell function genes,
      including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted
      proliferation of INS-1 beta-cells and upregulated Ki67 expression by mediating
      cell cycle progression. In addition, KLD-F improved beta-cell function and
      proliferation via an integrin/focal adhesion kinase/extracellular signal
      regulated kinase/cyclin D pathway. This study highlights the fact that the beta
      cell-ECM interaction reestablished with this functionalized self-assembling
      peptide is a promising method to improve the therapeutic efficacy of islet
      transplantation. 

PMID- 25999716
TI  - Accelerated blood clearance phenomenon upon cross-administration of PEGylated
      nanocarriers in beagle dogs.
AB  - The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG),
      named PEGylated nanocarriers, a type of combination therapy, is becoming an
      increasingly important method of long-term drug delivery, to decrease side
      effects, avoid multidrug resistance, and increase therapeutic efficacy. However,
      repeated injections of PEGylated nanocarriers induces the accelerated blood
      clearance (ABC) phenomenon, prevents long circulation, and can cause adverse
      effects owing to alterations in the biodistribution of the drug. Although the
      nature of the ABC phenomenon that is induced by repeated injections of PEGylated
      nanocarriers has already been studied in detail, there are few reports on the
      immune response elicited by the cross-administration of PEGylated nanocarriers.
      In this study, we investigated the ABC phenomenon induced by the intravenous
      cross-administration of various PEGylated nanocarriers, including PEGylated
      liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN),
      and PEGylated emulsions (PE), in beagle dogs. The results indicated that the
      magnitude of the immune response elicited by the cross-administration was in the
      following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is
      specifically PEG in the brush structure that elicits a significant immune
      response, in both the induction phase and the effectuation phase. Furthermore,
      the present study suggests that there is a considerable difference between the
      effect of repeated injections and cross-administration, depending on the
      colloidal structure. This work is a preliminary investigation into the cross
      administration of PEGylated nanocarriers, and our observations can have serious
      implications for the design of combination therapies that use PEGylated vectors. 

PMID- 25999719
TI  - Amalgamation of complex iron(III) ions and iron nanoclusters with MWCNTs as a
      route to potential T2 MRI contrast agents.
AB  - Iron-filled multiwall carbon nanotubes (Fe@MWCNTs) were functionalized toward a
      variety of potential magnetic resonance imaging contrast agents. Oxidized
      Fe@MWNCTs were covered with PEG5000 via direct esterification or using acyl
      chloride derivatives. Alternatively, the latter were functionalized with an
      aminophenol ligand (Fe@O-MWCNT-L). Moreover, pristine Fe@MWCNTs were
      functionalized with N-phenylaziridine groups (Fe@f-MWCNT) via [2+1] cycloaddition
      of nitrene. All of these chemically modified nanotubes served as a vehicle for
      anchoring Fe(3+) ions. The new hybrids--Fe(III)/Fe@(f-/O-)MWCNTs--containing 6%
      14% of the "tethered" Fe(3+) ions were studied in terms of the acceleration of
      relaxation of water protons in nuclear magnetic resonance. The highest transverse
      relaxivity r2=63.9+/-0.9 mL mg(-1) s(-1) was recorded for Fe(III)/Fe@O-MWCNT-L,
      while for Fe(III)/Fe@f-MWCNT, with r2=57.9+/-2.9 mL mg(-1) s(-1), the highest
      impact of the anchored Fe(III) ions was observed. The T1/T2 ratio of 30-100 found
      for all of the nanotube hybrids presented in this work is a very important factor
      for their potential application as T2 contrast agents. Increased stability of the
      hybrids was confirmed by ultraviolet-visible spectrophotometry.

PMID- 25999718
TI  - A single dose of dexamethasone encapsulated in polyethylene glycol-coated
      polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following
      round window membrane administration.
AB  - This study aimed to investigate the sustained drug release properties and hearing
      protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth
      nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA
      nanoparticles using an emulsion and evaporation technique, as previously
      reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic
      diameter of 130+/-4.78 nm, and a zeta potential of -26.13+/-3.28 mV. The in vitro
      release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4),
      5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6
      labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated
      RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral
      ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto
      the RWM of guinea pigs by a single-dose administration continuously released DEX
      in 48 hours, which was significantly longer than the free DEX that was cleared
      out within 12 hours after administration at the same dose. Further functional
      studies showed that locally administrated single-dose DEX-NPs effectively
      preserved outer hair cells in guinea pigs after cisplatin insult and thus
      significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when
      compared to the control of free DEX formulation. Histological analyses indicated
      that the administration of DEX-NPs did not induce local inflammatory responses.
      Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM
      diffusion (administration) significantly protected the hair cells and auditory
      function in guinea pigs from cisplatin toxicity, as determined at both
      histological and functional levels, suggesting the potential therapeutic benefits
      in clinical applications. 

PMID- 25999720
TI  - Profile of agomelatine and its potential in the treatment of generalized anxiety
      disorder.
AB  - BACKGROUND: Although many generalized anxiety disorder (GAD) patients respond to
      the available pharmacological treatments, nearly half of them do not present the
      expected results. Besides, the side effects associated to some drugs have a
      negative impact on treatment adherence. Therefore, the aim of this review was to
      report the clinical profile of agomelatine, a selective melatonergic MT1/MT2
      receptor agonist with serotonin 5-HT2c receptor antagonist activities, as a
      potential pharmacological option in the treatment of GAD. METHODS: We performed a
      literature review regarding studies that evaluated the use of agomelatine in GAD
      treatment. RESULTS: Two short-term, double-blinded studies and one prevention
      treatment trial evaluated the efficacy of agomelatine in the treatment of GAD.
      Agomelatine was associated with higher rates of clinical response and remission,
      when compared to placebo. In addition, the long-term use of agomelatine decreased
      the risk of relapse of anxiety symptoms, even for the severely ill patients.
      Besides, the tolerability was satisfactory with the absence of discontinuation
      symptoms, as observed in previous studies. CONCLUSION: The efficacy and
      tolerability profiles of agomelatine in the treatment of GAD were good. However,
      the scarce number of trials, the small sample sizes, and the use of patients
      without any comorbid conditions were some limitations that impaired the
      generalization of the results in the general population. Nevertheless,
      agomelatine is an attractive off-label option in the treatment of GAD that needs
      more conclusive evidences to establish its role in future guidelines.

PMID- 25999721
TI  - Wearing-off in Parkinson's disease: neuropsychological differences between on and
      off periods.
AB  - BACKGROUND: Levodopa-associated motor fluctuations are common complications
      observed in Parkinson's disease (PD) patients. Although nonmotor fluctuations are
      a significant cause of morbidity, they frequently are not properly identified.
      Few studies have characterized the nonmotor emotional fluctuations and their
      relation to motor fluctuations. AIMS: The objective of the present study is to
      analyze the occurrence of fluctuations in anxiety and depression symptoms, as
      well as in cognitive function (memory, language, executive function, and
      attention), and their relation to motor fluctuations in PD patients presenting
      wearing-off phenomenon. METHODS: Twenty-four patients were assessed during the
      wearing on-off periods. The State-Trait Anxiety Inventory (STAI-State) and Beck
      Depression Inventory (BDI) were used to assess anxiety and depression,
      respectively, and the Wisconsin Card Sorting Test (WCST), Stroop Test, Rey
      Auditory Verbal Learning Test (RAVLT), Weschler Memory Scale - digits (WMS) and
      Controlled Oral Word Association (COWA) for assessing executive functions, verbal
      memory, attention and work memory and verbal fluency, respectively. RESULTS:
      Patients presented higher depression and anxiety scores in the wearing-off period
      (P<0.05). Differences were also found in the semantic verbal fluency (P=0.017)
      and executive function (P=0.008) tests performance. CONCLUSIONS: Nonmotor
      symptoms such as anxiety and depression, verbal fluency, and executive function
      performance are influenced by motor fluctuations.

PMID- 25999717
TI  - Application of dental nanomaterials: potential toxicity to the central nervous
      system.
AB  - Nanomaterials are defined as materials with one or more external dimensions with
      a size of 1-100 nm. Such materials possess typical nanostructure-dependent
      properties (eg, chemical, biological, optical, mechanical, and magnetic), which
      may differ greatly from the properties of their bulk counterparts. In recent
      years, nanomaterials have been widely used in the production of dental materials,
      particularly in light polymerization composite resins and bonding systems,
      coating materials for dental implants, bioceramics, endodontic sealers, and
      mouthwashes. However, the dental applications of nanomaterials yield not only a
      significant improvement in clinical treatments but also growing concerns
      regarding their biosecurity. The brain is well protected by the blood-brain
      barrier (BBB), which separates the blood from the cerebral parenchyma. However,
      in recent years, many studies have found that nanoparticles (NPs), including
      nanocarriers, can transport through the BBB and locate in the central nervous
      system (CNS). Because the CNS may be a potential target organ of the
      nanomaterials, it is essential to determine the neurotoxic effects of NPs. In
      this review, possible dental nanomaterials and their pathways into the CNS are
      discussed, as well as related neurotoxicity effects underlying the in vitro and
      in vivo studies. Finally, we analyze the limitations of the current testing
      methods on the toxicological effects of nanomaterials. This review contributes to
      a better understanding of the nano-related risks to the CNS as well as the
      further development of safety assessment systems. 

PMID- 25999722
TI  - The cortisol awakening response and major depression: examining the evidence.
AB  - A vast body of literature has revealed that dysregulation of the hypothalamic
      pituitary-adrenal (HPA) stress axis is associated with etiology of major
      depressive disorder (MDD). There are many ways that the dysregulation of the HPA
      axis can be assessed: by sampling diurnal basal secretion and/or in response to a
      stress task, pharmacological challenge, and awakening. Here, we focus on the
      association between cortisol awakening response (CAR), as one index of HPA axis
      function, and MDD, given that the nature of this association is particularly
      unclear. Indeed, in the following selective review, we attempt to reconcile
      sometimes-divergent evidence of the role of CAR in the pathway to depression. We
      first examine association of CAR with psychological factors that have been linked
      with increased vulnerability to develop depression. Then, we summarize the
      findings regarding the CAR profile in those with current depression, and evaluate
      evidence for the role of CAR following depression resolution and continued
      vulnerability. Finally, we showcase longitudinal studies showing the role of CAR
      in predicting depression onset and recurrence. Overall, the studies reveal an
      important, but complex, association between CAR and vulnerability to depression. 

PMID- 25999723
TI  - Update on the management of chemotherapy-induced nausea and vomiting - focus on
      palonosetron.
AB  - PURPOSE: Nausea and vomiting are major adverse effects of chemotherapy and can
      greatly impact patients' quality of life. Although chemotherapy-induced nausea
      and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron
      is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of
      CINV. The purpose of this review is to discuss existing and emerging therapeutic
      options, and examine studies focusing on palonosetron with regards to efficacy,
      pharmacology, tolerability, safety, and patient-derived outcomes. METHODS: A
      literature search was conducted using Ovid MEDLINE and EMBASE to identify
      relevant studies using palonosetron alone or in combination with other
      antiemetics. Studies were extracted if they included complete response (CR),
      complete control (CC), no nausea, no vomiting, and no rescue medications as an
      endpoint. Studies were also included if safety endpoints were examined. RESULTS:
      Palonosetron alone has been shown to improve CR and CC rates for patients
      receiving low, moderate, or high emetogenic chemotherapy. Rates were further
      improved with the addition of dexamethasone, a corticosteroid. Furthermore, the
      addition of neurokinin-1 receptor antagonists, such as netupitant markedly
      improved efficacy profiles compared to palonosetron alone. Aprepitant is an
      antiemetic that has exhibited positive results in combination with palonosetron.
      Recently, a new drug consisting of netupitant and palonosetron (NEPA) has
      demonstrated significantly more efficacious prevention of CINV. Regardless of the
      combination, palonosetron has been well tolerated. The most common adverse events
      were constipation, headache, fatigue, and dizziness, with the majority of
      patients describing them as only mild or moderate. CONCLUSION: Palonosetron,
      alone or with other antiemetics, has improved CINV treatment due to its ability
      to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs.
      Palonosetron is both more effective than first generation 5-HT3RAs and safer, as
      it results in a smaller prolongation of the QTc interval, compared to other 5
      HT3RAs.

PMID- 25999724
TI  - Recurrent respiratory papillomatosis: current and future perspectives.
AB  - Although recurrent respiratory papillomatosis is a benign disease of the upper
      aerodigestive tract caused by infection with human papillomavirus, the disease
      process is unpredictable, ranging from mild disease and spontaneous remission to
      an aggressive disease with pulmonary spread and requirement for frequent surgical
      debulking procedures. It can present a protracted clinical course and cause
      potentially life-threatening compromise of the airways. Over recent decades, a
      number of alternative medical therapies to standard surgical treatment have been
      investigated, with modest outcomes overall. Currently, some additional therapies
      are being explored, together with novel surgical instrumentation that can help to
      avoid inevitable long-term stenotic complications, ultimately affecting quality
      of life. Hopefully, clinicians might soon be able to significantly improve the
      quality of treatment and outcomes for patients affected with recurrent
      respiratory papillomatosis, with human papillomavirus vaccination having a
      potentially important role. 

PMID- 25999725
TI  - The role of empagliflozin in the management of type 2 diabetes by patient
      profile.
AB  - Current recommendations for the management of type 2 diabetes mellitus (T2DM)
      include patient-centered approach, ie, targeting glycemic control based on
      patient and disease characteristics. Ten different classes of oral and injectable
      anti-hyperglycemic agents have been developed for T2DM, including the newest
      class - sodium-glucose cotransporter 2 (SGLT2) inhibitors. Four members of the
      class with comparable glycemic efficacy and side effects have gained approval in
      the US and the rest of the world. This review covers empagliflozin - third
      approved SGLT2 inhibitor in the US. The drug has shown rapid absorption reaching
      peak levels in ~2 hours and an elimination half-life of ~13 hours. Empagliflozin
      is a highly selective SGLT2 inhibitor with 2600-fold higher affinity for SGLT2
      compared with SGLT1. Oral administration results in a dose-dependent inhibition
      of the transporters with increased urinary glucose excretion and resultant
      reduction in plasma glucose. Its efficacy and safety have been shown in a number
      of studies conducted in many countries. Across the trials, significant
      improvements in primary and secondary efficacy end points have been demonstrated,
      including reductions in HbA1c (~-0.8%), fasting plasma glucose (~-2 mmol/L), body
      weight (~-2 kg), and blood pressure (systolic -4 mmHg and diastolic -2 mmHg).
      Similar to other SGLT2 inhibitors, empagliflozin does not increase the risk for
      hypoglycemia, and the most commonly reported side effects are urinary and genital
      tract infections. Although empagliflozin can be used as the first-line
      monotherapy, its current place in the treatment of T2DM appears to be as an add
      on to other oral anti-hyperglycemic agent(s) or insulin at any stage of the
      disease. 

PMID- 25999726
TI  - The role of delamanid in the treatment of drug-resistant tuberculosis.
AB  - Tuberculosis (TB) remains a significant cause of death worldwide, and emergence
      of drug-resistant TB requires lengthy treatments with toxic drugs that are less
      effective than their first-line equivalents. New treatments are urgently needed.
      Delamanid, previously OPC-67863, is a novel drug of the dihydro-nitroimidazole
      class with potent anti-TB activity and great promise to be effective in the
      treatment of drug-resistant TB. This review examines the preclinical and clinical
      development of delamanid, reviews current guidance on its use and evaluates the
      opportunities and challenges for its future role in TB management. 

PMID- 25999727
TI  - Testosterone levels of children with a diagnosis of developmental stuttering.
AB  - BACKGROUND: Stuttering is defined as a disruption in the rhythm of speech and
      language articulation, where the subject knows what he/she wants to say, but is
      unable to utter the intended word or phrase fluently. The effect of sex on
      development and chronicity of stuttering is well known; it is more common and
      chronic in males. We aimed to investigate the relationship between developmental
      stuttering and serum testosterone levels in this study. MATERIALS AND METHODS: In
      this study, we evaluated a total of 50 children (7-12 years of age); eight (16%)
      were female and 42 (84%) were male. Twenty-five children who stutter and 25
      typically fluent peers with the same demographic properties (ages between 7 years
      and 12 years) were included in this study. The testosterone levels of the two
      groups were determined in terms of nanogram per milliliter (ng/mL) by enzyme
      linked immunosorbent assay. The difference between the means of the two groups
      was analyzed. RESULTS: The medians of the testosterone levels of the stutterer
      and control groups were determined as 20 ng/mL (range =12-184 ng/mL) and 5 ng/mL
      (range =2-30 ng/mL), respectively. Testosterone levels of the stutterer group
      were significantly higher than in the control group (P=0.001). Besides, there was
      a significant correlation between the severity of the stuttering and testosterone
      levels in the stutterer group (P=0.0001). CONCLUSION: The findings of this study
      show that testosterone may have an effect on the severity of developmental
      stuttering and on the clinical differences between sexes. However, further
      investigations are needed to show that testosterone may play a role in the
      etiology of developmental stuttering.

PMID- 25999728
TI  - Management of patients with type 2 diabetes and mild/moderate renal impairment:
      profile of linagliptin.
AB  - Dipeptidyl-peptidase-IV (DPP-4) inhibitors are oral antidiabetic agents that can
      be administered as monotherapy in patients with contraindications to metformin or
      metformin intolerance, and in combination with other oral compounds and/or
      insulin. DPP-4 inhibitors act in a glucose-dependent manner and only increase
      insulin secretion and inhibit glucagon secretion under hyperglycemic conditions.
      Renal impairment is frequent in type 2 diabetes as a result of microvascular
      complications and diabetes treatment, and options in these patients are limited.
      Linagliptin is a DPP-4 inhibitor with a hepatobiliary route of elimination. In
      comparative studies, it was noninferior to metformin and sulfonylureas in
      lowering glycated hemoglobin (HbA1c) and improving glycemic parameters. It can be
      used throughout all stages of renal impairment without dose adjustments. This
      review gives an overview of linagliptin in various stages of chronic kidney
      disease and has a focus on efficacy and safety parameters from clinical studies
      in patients with impaired renal function. These data are interpreted in the
      context of type 2 diabetes therapy in general. 

PMID- 25999729
TI  - Lipid-modifying therapy in the elderly.
AB  - Cardiovascular disease (CVD) mortality and morbidity increases with increasing
      age, largely as a result of increased lifetime exposure as well as increased
      prevalence of CVD risk factors. Hospitalization for CVD increases by a factor of
      over 18* for those aged 85+ years versus those aged <30 years. In spite of this,
      life expectancy continues to increase, and in Australia for people reaching the
      age of 65 years, it is now 84 years in men and 87 years in women. The number of
      people for whom lipid management is potentially indicated therefore increases
      with aging. This is especially the case for secondary prevention and for people
      aged 65-75 years for whom there is also evidence of benefit from primary
      prevention. Many people in this age group are not treated with lipid-lowering
      drugs, however. Even those with CVD may be suboptimally treated, with one study
      showing treatment rates to fall from ~60% in those aged <50 years to <15% for
      those aged 85+ years. Treatment of the most elderly patient groups remains
      controversial partly from the lack of randomized trial intervention data and
      partly from the potential for adverse effects of lipid therapy. There are many
      complex issues involved in the decision to introduce effective lipid-lowering
      therapy and, unfortunately, in many instances there is not adequate data to make
      evidence-based decisions regarding management. This review summarizes the current
      state of knowledge of the management of lipid disorders in the elderly and
      proposes guidelines for management. 

PMID- 25999731
TI  - Impact of an educational intervention on provider knowledge, attitudes, and
      comfort level regarding counseling women ages 40-49 about breast cancer
      screening.
AB  - BACKGROUND: Mammography screening for women under the age of 50 is controversial.
      Groups such as the US Preventive Services Task Force recommend counseling women
      40-49 years of age about mammography risks and benefits in order to incorporate
      the individual patient's values in decisions regarding screening. We assessed the
      impact of a brief educational intervention on the knowledge and attitudes of
      clinicians regarding breast cancer screening. METHODS: The educational
      intervention included a review of the risks and benefits of screening, individual
      risk assessment, and counseling methods. Sessions were led by a physician expert
      in breast cancer screening. Participants were physicians and nurses in 13 US
      Department of Veterans Affairs primary care clinics in Alabama. Outcomes were as
      follows: 1) knowledge assessment of mammogram screening recommendations; 2)
      counseling practices on the risks and benefits of screening; and 3) comfort level
      with counseling about screening. Outcomes were assessed by survey before and
      after the intervention. RESULTS: After the intervention, significant changes in
      attitudes about breast cancer screening were seen. There was a decrease in the
      percentage of participants who reported that they would screen all women ages 40
      49 years (82% before the intervention, 9% afterward). There was an increase in
      the percentage of participants who reported that they would wait until the
      patient was 50 years old before beginning to screen (12% before the intervention,
      38% afterward). More participants (5% before, 53% after; P<0.001) said that they
      would discuss the patient's preferences. Attitudes favoring discussion of
      screening benefits increased, though not significantly, from 94% to 99%
      (P=0.076). Attitudes favoring discussion of screening risks increased from 34% to
      90% (P<0.001). The comfort level with discussing benefits increased from a mean
      of 3.8 to a mean of 4.5 (P<0.001); the comfort level with discussing screening
      risks increased from 2.7 to 4.3 (P<0.001); and the comfort level with discussing
      cancer risks and screening preferences with patients increased from 3.2 to 4.3
      (P<0.001). (The comfort levels measurements were assessed by using a Likert
      scale, for which 1= not comfortable and 5= very comfortable.). CONCLUSION: Most
      clinicians in the US Department of Veterans Affairs ambulatory practices in
      Alabama reported that they routinely discuss mammography benefits but not
      potential harms with patients. An educational intervention detailing
      recommendations and counseling methods affected the knowledge and attitudes about
      breast cancer screening. Participants expressed greater likelihood of discussing
      screening options in the future.

PMID- 25999730
TI  - Epoprostenol sodium for treatment of pulmonary arterial hypertension.
AB  - The release of endogenous prostacyclin (PGI2) is depressed in patients with
      pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol
      infusion is one of the best treatments available for PAH. Here, we provide an
      overview of the current clinical data for epoprostenol. Epoprostenol treatment
      improves symptoms, exercise capacity, and hemodynamics, and is the only treatment
      that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in
      randomized clinical trials. We have reported that high-dose epoprostenol therapy
      (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients
      with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via
      the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long
      term intravenous administration of epoprostenol is sometimes associated with
      catheter-related infections and leads to considerable inconvenience for the
      patient. In the future, the development of new routes of administration or the
      development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell
      based therapy enhancing PGI2 production with new routes of administration is
      required. 

PMID- 25999732
TI  - An analysis of brachytherapy with computed tomography-guided permanent
      implantation of Iodine-125 seeds for recurrent nonkeratin nasopharyngeal
      carcinoma.
AB  - BACKGROUND: (125)I seed implantation is a new method in treatment of
      nasopharyngeal carcinoma (NPC), and it is worthwhile to evaluate its feasibility.
      In this study, we performed brachytherapy with computed tomography (CT)-guided
      permanent implantation of (125)I seeds in the treatment of patients with the
      recurrence of NPC. METHODS: A total 30 patients (20 male and ten female) at the
      median age of 55 (range 25-80) years were diagnosed with recurrent nonkeratin
      NPC, with a total 38 lesions and a short disease-free interval (median11 months)
      after primary radiotherapy alone or combined with chemotherapy. Patients received
      CT scan, starting from 2 months after the treatment. Follow-up was conducted for
      ~2-38 months to observe the local control rate and overall survival rate. We also
      analyzed the possible correlation between survival periods and the status of
      recurrent tumors. RESULTS: The local control rates at 6, 12, 24, 30, and 36
      months after the procedure of (125)I seed implantation were 86.8%, 73.7%, 26.3%,
      15.8%, and 5.3%, respectively. The overall 1-, 2-, and 3-year survival rates were
      80.0% (24/30), 30.0% (9/30), and 6.7% (2/30), respectively, with a median
      survival period of 18 months (17.6+/-8.6 months). Interestingly, the survival
      periods of the patients who had primary radiotherapy with or without chemotherapy
      were 15.8+/-7.9 and 24.3+/-7.9 months, respectively. Kaplan-Meier survival
      analysis demonstrated that chi (2) (log rank) was 7.555, with very significant
      difference (P<0.01). The survival periods of patients in tumor stages I, II, III,
      and IV were 25.4+/-8.7, 19.8+/-9.4, 16.1+/-4.5, and 12.8+/-7.8 months,
      respectively, with significant differences (P<0.05). CONCLUSION: Our data suggest
      that the survival period of recurrent NPC patients after (125)I seed implantation
      is inversely related to the tumor stages of the recurrence but not to
      chemotherapy after the primary radiotherapy. Therefore, CT-guided (125)I seed
      implantation can be set for treatment of recurrent NPC, for better survival rate
      with minimal damage.

PMID- 25999733
TI  - Personalized treatment strategies for non-small-cell lung cancer in Chinese
      patients: the role of crizotinib.
AB  - Anaplastic lymphoma kinase (ALK) rearrangement is an oncogene targeted with
      approved drugs second to epidermal growth factor receptor (EGFR) in lung cancer.
      Crizotinib was developed and introduced into clinical practice rapidly and
      successfully after the discovery of ALK rearrangement in non-small-cell lung
      cancer. Chinese and other Asian patients treated with crizotinib seem to have
      lower toxicity and higher efficacy compared with other ethnicities. Crizotinib
      showed potent antitumor activity and manageable toxicity in mesenchymal
      epithelial transition factor (c-Met)/ROS1-positive non-small-cell lung cancer
      patients, but prospective clinical trials are still needed to confirm its
      efficacy and safety. Crizotinib appears to be effective against tumors
      originating from various organs that harbor ALK abnormalities. In the near
      future, we would classify the tumors by their genetic information beyond organs,
      such as ALKoma, EGFRoma, and RAFoma, and a single compound could be used for many
      different types of cancer in different organs. The major challenge of the
      widespread use of crizotinib in clinical practice is establishing convenient
      diagnostic techniques for the detection of ALK/c-Met/ROS1. In the present study,
      we reviewed the application of crizotinib in Chinese patients. 

PMID- 25999734
TI  - ABCB1 C3435T polymorphism is associated with leukemia susceptibility: evidence
      from a meta-analysis.
AB  - INTRODUCTION AND OBJECTIVE: Many studies have been conducted on the association
      between the adenosine triphosphate-binding cassette, subfamily B, member 1
      (ABCB1) gene C3435T polymorphism and leukemia risk, however, the previously
      published findings remain controversial. Thus, a meta-analysis was carried out to
      accurately evaluate the effect of this polymorphism on leukemia susceptibility.
      METHODS: A computerized literature search was conducted of PubMed, Elsevier
      database, the China National Knowledge Infrastructure database, and Wanfang
      Database, to find published case-control studies exploring the relationship
      between ABCB1 C3435T polymorphism and leukemia risk. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were applied to assess the strength of association.
      RESULTS: A total of 17 studies of 2,431 cases and 3,028 controls were included in
      this meta-analysis. The results of overall comparisons suggest that there is a
      significant association between ABCB1 C3435T polymorphism and leukemia risk under
      two genetic models (TT vs CC: OR=1.39, 95% CI=1.04-1.84, P=0.02; CT+TT vs CC:
      OR=1.20, 95% CI=1.06-1.36, P=0.004). In the subgroup analyses by ethnicity, age,
      and leukemia subtype, a significant association was found in Caucasian (CT vs CC:
      OR=1.22, 95% CI=1.03-1.45, P=0.02; TT vs CC: OR=1.34, 95% CI=1.10-1.64, P=0.004;
      CT+TT vs CC: OR=1.27, 95% CI=1.08-1.49, P=0.004), adult leukemia (CT vs CC:
      OR=1.46, 95% CI=1.17-1.83, P=0.001; CT+TT vs CC: OR=1.43, 95% CI=1.01-2.03,
      P=0.04), and lymphocytic leukemia (TT vs CC: OR=1.73, 95% CI=1.19-2.51, P=0.004;
      TT vs CC+CT: OR=1.62, 95% CI=1.10-2.38, P=0.01; CT+TT vs CC: OR=1.28, 95% CI=1.10
      1.48, P=0.001). CONCLUSION: The meta-analysis suggests that ABCB1 C3435T
      polymorphism is associated with increased risk of leukemia.

PMID- 25999735
TI  - GCDFP-15, AR, and Her-2 as biomarkers for primary ductal adenocarcinoma of the
      lacrimal gland: a Chinese case and literature review.
AB  - PURPOSE: Primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare
      malignant epithelial tumor, and its clinicopathological characteristics are still
      unclear. This study aimed to report a novel case of PDA of the lacrimal gland in
      the People's Republic of China, as well as to determine its histopathological and
      immunohistochemical characteristics to support early diagnosis and direct further
      therapy. PATIENT AND METHODS: Clinical data (including ocular examination,
      computed tomography, magnetic resonance imaging, positron emission tomography,
      mammography, and serum tumor marker examination) and treatment of a 49-year-old
      woman with a left lacrimal gland mass, which was diagnosed as PDA of the lacrimal
      gland, were reported. Histopathological and immunohistochemical studies were
      performed. Eleven papers regarding this uncommon neoplasm were reviewed. RESULTS:
      Histopathologically, most of the tumor cells featured abundant granular
      eosinophilic cytoplasm, while few of them had a frothy appearance. The mass
      showed breast ductal carcinoma-like structural features, which most commonly
      demonstrated central necrosis, while less of these features showed cord-like
      infiltration. Immunohistochemically, the tumor cells were positive for GCDFP-15,
      CK 18 (++), AR (90%), Her-2 (+++), P53 (100%), and Ki-67 (with a proliferation
      index approximately 60%), while they were negative for ER, PR, P63, calponin, and
      CD 117. CONCLUSION: This was the first Chinese case of PDA of the lacrimal gland
      that had been reported. We suggested that GCDFP-15, AR, and Her-2 should be
      tested as biomarkers for ductal adenocarcinoma of lacrimal gland to confirm
      diagnosis, guide therapy, and further predict prognosis.

PMID- 25999736
TI  - Evaluation of clinical breast examination and breast ultrasonography among
      pregnant women in Abakaliki, Nigeria.
AB  - BACKGROUND: Breast cancer in pregnancy accounts for 2%-3% of all breast cancers.
      The increased vascularity and lymphatic drainage from the breast during pregnancy
      potentiate the metastatic spread of the cancer to the regional lymph nodes.
      However, the increased breast density in pregnancy makes it difficult to detect
      breast lesions early. AIM: To evaluate and compare the detection rate of breast
      lesions using clinical breast examination (CBE) and breast ultrasonography among
      pregnant women. METHODOLOGY: A cross-sectional comparative study involving
      antenatal clinic attendees at the Federal Teaching Hospital, Abakaliki, was
      conducted between March 3, 2014, and December 31, 2014. CBE and breast
      ultrasonography were done in the participants at booking and repeated at 6 weeks
      postpartum. Fine-needle aspiration cytology and histology were done in women with
      suspicious breast lesions on CBE or breast ultrasonography or both. Data analysis
      was both descriptive and inferential at the 95% confidence level using the
      Statistical Package for the Social Sciences (SPSS) software version 17.0. Test of
      significance was done using chi-square test. A P-value of less than or equal to
      0.05 was considered statistically significant. RESULTS: A total of 320 pregnant
      women participated in the study. Of these, 267 (83.4%) were aware of breast
      cancer. Although more lesions were detected with breast ultrasonography than by
      CBE, there was no statistically significant difference between them (25 versus
      17; P=0.26). The histology of the lesions revealed 21 benign lesions and 4 normal
      breast tissues. The sensitivity of breast ultrasonography was 95.2%, while that
      of CBE was 66.7%. The specificity, positive predictive value, and negative
      predictive value were similar between CBE and breast ultrasonography. CONCLUSION:
      The detection rates of breast lesions by both CBE and breast ultrasonography were
      equivalent during pregnancy and 6 weeks postpartum, making CBE a convenient and
      very cost-effective method of detecting breast lesions in the low-risk
      population. However, both CBE and breast ultrasonography should be done in women
      with high risk of breast malignancy.

PMID- 25999737
TI  - Lung cancer drug therapy in Hungary - 3-year experience.
AB  - Hungary is a world leader in lung cancer deaths, so it is of crucial importance
      that patients have access to modern treatments. The aim of our analysis was to
      explore how drug treatments are used in Hungary and how they are compatible with
      international practice. The inpatient and prescription database of the National
      Health Insurance Fund Administration of Hungary was used to study the frequency
      of certain chemotherapy protocols and duration of therapies during a 3-year
      period (2008-2010). During the study period, 12,326 lung cancer patients received
      first-line chemotherapy, a third of those (n=3,791) received second-line
      treatment, and a third of the latter (n=1,174) received third-line treatment. The
      average treatment duration was between 3 and 4 months. The first-line treatment
      of non-small-cell lung carcinoma mainly consisted of platinum treatment in
      combination with third-generation cytotoxic agents. A downward trend of
      gemcitabine, still the most common combination compound, was observed, in
      parallel with a significantly increased use of paclitaxel, and as a consequence
      carboplatin replaced cisplatin. Among the new agents, the use of pemetrexed and
      bevacizumab increased. Pemetrexed appeared mainly in second-line treatment, while
      erlotinib appeared also in second-line but mostly in third-line treatments. The
      first-line treatment of small-cell lung carcinoma consisted of a platinum
      etoposide combination, while in the second-line setting topotecan was the most
      commonly used drug. According to our results, the chemotherapeutic combinations
      and sequencing are in accordance with international and national recommendations.
      Further detailed analysis of the available data may help to obtain a more
      accurate picture of the efficacy of lung cancer treatments as well. 

PMID- 25999738
TI  - Metastatic medullary thyroid cancer: a dramatic response to a systemic
      chemotherapy (temozolomide and capecitabine) regimen.
AB  - A 40-year-old male patient presented with increasing serum levels of calcitonin
      and CEA. He underwent potential curative surgery for medullary thyroid carcinoma,
      3 years ago and then 7 months later he had metastasectomy and cervical lymph node
      dissection for recurrent disease. On admission he had multiple metastatic skin
      nodules on the chest wall and positron emission tomography-computed tomography
      revealed multiple visceral metastases as well. The patient had not received any
      systemic treatment up to that time; therefore, we considered systemic treatment
      with the new tyrosine kinase inhibitors (vandetanib, cabozantinib, etc). However,
      since these drugs are only available after cytotoxic chemotherapy, we started
      temozolomide and capecitabine chemotherapy. After two courses of the treatment
      all skin nodules disappeared and CEA and calcitonin levels normalized,
      radiological imaging showed a good partial response. 

PMID- 25999739
TI  - Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces
      apoptosis, and reduces viability and migration of PLX4032-resistant melanoma
      cells.
AB  - Melanoma is the deadliest form of skin cancer, and BRAFV600E is a driver mutation
      that promotes melanoma growth and survival. PLX4032 is the first effective
      compound in clinical use for the treatment of patients with mutant BRAFV600.
      However, resistance to PLX4032 develops quickly within months. Activation of a
      series of receptor tyrosine kinases, including the platelet-derived growth factor
      receptor (PDGFR), has been identified to be the underlying mechanism for
      development of resistance to PLX4032. In this work, we investigated the
      anticancer activity of tyrphostin AG1296, a PDGFR inhibitor, in melanoma,
      especially PLX4032-resistant melanoma. We found that tyrphostin AG1296 could
      effectively reduce the viability of both PLX4032-sensitive and PLX4032-resistant
      melanoma cells. There is an additive effect between tyrphostin AG1296 and PLX4032
      in reducing cell viability. Tyrphostin AG1296 induced dramatic apoptosis in
      PLX4032-resistant cells, and also dramatically inhibited migration of PLX4032
      resistant cells. Importantly, tyrphostin AG1296 significantly suppressed A375R
      tumor growth in vivo. This is the first report on the anticancer activity of
      tyrphostin AG1296 in melanoma. Tyrphostin AG1296 is a promising compound in the
      treatment of melanoma, especially for those who have developed resistance towards
      BRAF inhibitors, and might shed new light on melanoma therapy. 

PMID- 25999740
TI  - Primary paraesophageal Ewing's sarcoma: an uncommon case report and literature
      review.
AB  - Ewing's sarcoma is a rare and highly aggressive cancer most frequently arising in
      people under 20 years of age. We report an uncommon case of primary
      paraesophageal Ewing's sarcoma in a 25-year-old male harboring the infrequent
      EWSR1/ERG fusion transcript with multiple splice variants coexisting in the same
      tumor. The patient was totally refractory to chemotherapy and died 17 months
      after diagnosis. We underscore the need for better understanding of the molecular
      pathogenesis of the disease and improved systemic therapy options. 

PMID- 25999741
TI  - A randomized Phase II clinical study of combining panitumumab and bevacizumab,
      plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) compared with FOLFIRI
      alone as second-line treatment for patients with metastatic colorectal cancer and
      KRAS mutation.
AB  - BACKGROUND: This study investigated the efficacy and safety of a new treatment
      strategy of combining panitumumab and bevacizumab, plus irinotecan, 5
      fluorouracil, and leucovorin (FOLFIRI) versus FOLFIRI alone as second-line
      chemotherapy for metastatic colorectal cancer (mCRC) patients with known V-Ki
      ras2 Kirsten rat sarcoma viral oncogene (KRAS) mutation status. METHODS: Patients
      with mCRC who had known KRAS tumor status and unsuccessful previous oxaliplatin
      based chemotherapy were included in the study. They were randomly assigned to two
      groups to receive panitumumab and bevacizumab plus FOLFIRI, or FOLFIRI alone. In
      panitumumab and bevacizumab plus FOLFIRI group, patients were given 4 mg/kg
      panitumumab and bevacizumab plus FOLFIRI every 2 weeks. RESULTS: In all, 65
      patients were assigned to panitumumab and bevacizumab plus FOLFIRI group, and 77
      to FOLFIRI alone group. For WT KRAS patients, the median progression-free
      survival (PFS) was 5.7 months (95% confidence interval [CI], 2.4-7.5 months) for
      panitumumab and bevacizumab plus FOLFIRI and 3.8 months (95% CI, 3.0-6.7 months)
      for FOLFIRI alone; median overall survival (OS) was 15.2 months (95% CI, 8.9-19.7
      months) for panitumumab and bevacizumab plus FOLFIRI and 11.0 months (95% CI, 8.2
      15.4 months) for FOLFIRI alone. For MU KRAS patients, median PFS was 5.1 months
      (95% CI, 2.7-10.2 months) for panitumumab and bevacizumab plus FOLFIRI and 4.1
      months (95% CI, 2.5-8.4 months) for FOLFIRI alone; median OS was 12.8 months (95%
      CI, 7.8-15.8 months) for panitumumab and bevacizumab plus FOLFIRI and 10.5 months
      (95% CI, 6.1-15.3 months) for FOLFIRI alone. Grade 3 and 4 adverse events were
      associated with panitumumab and bevacizumab plus FOLFIRI but tolerable among
      patients. CONCLUSION: Patients with mCRC can be safely and efficiently treated
      with second-line chemotherapy of combining panitumumab and bevacizumab plus
      FOLFIRI, despite their KRAS mutation status.

PMID- 25999742
TI  - Positive correlation between expression level of mitochondrial serine
      hydroxymethyltransferase and breast cancer grade.
AB  - Metabolic reprogramming plays an essential role in supporting the survival and
      proliferation of cancer cells. Serine hydroxymethyltransferase (SHMT) directs
      serine to the metabolism of one-carbon unit and the synthesis of thymidilate as a
      key factor in this metabolic shift. Although the mitochondrial isoform of SHMT
      (SHMT2) has been proven to be a crucial factor in the serine/glycine metabolism
      in several cancer cell types, the expression pattern of SHMT2 and the correlation
      of expression level of SHMT2 and other clinicopathological parameters in clinical
      breast cancer remain to be explored. In this research, 76 breast cancer patients
      who underwent modified radical mastectomy were enrolled for immunohistochemical
      analysis of the expression level of SHMT2 in their cancerous breast tissues for
      comparison with that in matching, distant noncancerous tissues. The results
      showed that SHMT2 was not expressed in the distant noncancerous cells. In
      contrast, SHMT2 protein could be stained in all breast cancer samples at varying
      degrees. Higher level of SHMT2 was expressed in grade III breast cancer cells
      than that those in grade I-II (P<0.05). In conclusion, SHMT2 was highly expressed
      in breast cancer cells, and the expression level of SHMT2 was positively
      correlated with breast cancer grade, suggesting that SHMT2 could be a target for
      anticancer therapies. 

PMID- 25999744
TI  - Current trends in the prevalence of Cryptococcus gattii in the United States and
      Canada.
AB  - The incidence of Cryptococcus gattii infections in both Canada and the United
      States (US) is provided in this literature review beyond the British Columbia
      (BC) outbreak (1999-2013). Based on a search of the literature, case reports of
      C. gattii human infections including the prevalent molecular genotypes causing
      these infections in both Canada and the US have been documented since the C.
      gattii outbreak in BC. The literature reveals that: i) although C. gattii
      infections continue to be reported in both countries, the preliminary overall
      number of confirmed C. gattii infections may be decreasing in both Canada and the
      US (~23 cases each in 2012 versus ~17 and 20 cases, respectively in 2013); ii) C.
      gattii genotype distribution is region-dependent; iii) C. gattii is more
      frequently isolated from infections in the immunocompromised host (including
      acquired immune deficiency syndrome [AIDS] infection) than previously expected;
      iv) although pulmonary disease is higher than in C. neoformans infections,
      central nervous system disease is also reported among patients infected with C.
      gattii. 

PMID- 25999745
TI  - bla CTX-M-I group extended spectrum beta lactamase-producing Salmonella typhi
      from hospitalized patients in Lagos, Nigeria.
AB  - PURPOSE: The global spread of bla CTX-M-I extended-spectrum beta-lactamase (ESBL)
      producing Salmonella spp. remains a major threat to treatment and control.
      Evidence of emergence and spread of this marker are lacking in Nigeria. This
      study investigated bla CTX-M-I ESBL production among Salmonella isolates from
      hospitalized patients. METHODS: Patients (158 total) made up of two groups were
      evaluated. Group A was composed of 135 patients with persistent pyrexia and group
      B was composed of 23 gastroenteritis patients and their stool samples. Samples
      were cultured, and isolates were identified and were subjected to antibiotic
      susceptibility testing by standard methods. Isolates were further screened for
      ESBL production, bla CTX-M-I genes and transferability by double disk synergy
      test, plasmid extraction, polymerase chain reaction, and conjugation experiment.
      RESULTS: Thirty-five (25.9%) Salmonella isolates were identified from group A, of
      which 74.3% were S. typhi, 22.9% were S. paratyphi and two (5.7%) were invasive
      non-typhoidal S. enteritidis. Nine Plasmodium falciparum infections were
      recorded, four of which were identified as co-infections with typhoidal
      Salmonella. Only two (8.7%) S. enteritidis samples were obtained from group B
      (P>0.05). A total of 24 isolates were ESBL-positive, eliciting resistance to five
      to seven antibiotics, and were multiple-drug resistant. ESBL production due to
      the bla CTX-M-I gene cluster was detected in eleven (45.8%) Salmonella isolates.
      Nine (81.8%) of the eleven bla CTX-M-I ESBL producers were S. typhi and two
      (18.2%) isolates were S. enteritidis. Four of nine S. typhi bla CTX-M-I ESBL
      producing strains harbored 23 kb self-transmissible plasmid that was co
      transferred with cefotaxime and augmentin resistance to Escherichia coli j53-2
      transconjugants. CONCLUSION: This study revealed the emergence of bla CTX-M-I S.
      typhi as an agent of persistent pyrexia with potential to spread to other
      Enterobacteriaceae in Lagos, Nigeria. Cautionary prescription and judicious use
      of third-generation cephalosporins, particularly cefotaxime, for the treatment of
      typhoid fever and routine screening for P. falciparum co-infection with ESBL
      producing Salmonella in the laboratories during diagnosis of persistent pyrexia
      conditions in patients are recommended.

PMID- 25999746
TI  - Validation of a phage-open reading frame typing kit for rapid identification of
      methicillin-resistant Staphylococcus aureus (MRSA) transmission in a tertiary
      hospital.
AB  - Surveillance is very important to prevent the nosocomial spread of methicillin
      resistant Staphylococcus aureus (MRSA), and infection sources and routes have
      historically been identified using molecular and epidemiological genotyping with
      pulsed-field gel electrophoresis. However, phage-open reading frame typing (POT)
      has recently been developed. Here, we investigated whether POT would be useful to
      survey MRSA outbreaks and transmission. We therefore applied POT to 91 MRSA
      isolates detected in cultures from inpatients at our hospital between May and
      October 2014. Among the 91 isolates, 12 POT types comprising 38 isolated MRSA
      strains were considered as overlapping. Five of them were detected in different
      wards, whereas the remaining seven were found in the same ward, including the
      emergency department. Three of seven POT number 93-155-111 strains were detected
      in the surgical ward, and all of four POT number 93-157-61 strains were detected
      in the cardiosurgical ward. These data suggested that transmission of the MRSA
      strains with the same POT-types from the same wards was nosocomial, and that POT
      accurately and rapidly identified MRSA strains, which allowed effective control
      of infection and transmission. 

PMID- 25999743
TI  - Cardiac tissue engineering and regeneration using cell-based therapy.
AB  - Stem cell therapy and tissue engineering represent a forefront of current
      research in the treatment of heart disease. With these technologies, advancements
      are being made into therapies for acute ischemic myocardial injury and chronic,
      otherwise nonreversible, myocardial failure. The current clinical management of
      cardiac ischemia deals with reestablishing perfusion to the heart but not dealing
      with the irreversible damage caused by the occlusion or stenosis of the supplying
      vessels. The applications of these new technologies are not yet fully established
      as part of the management of cardiac diseases but will become so in the near
      future. The discussion presented here reviews some of the pioneering works at
      this new frontier. Key results of allogeneic and autologous stem cell trials are
      presented, including the use of embryonic, bone marrow-derived, adipose-derived,
      and resident cardiac stem cells. 

PMID- 25999747
TI  - Polymerase chain reaction-based active surveillance of MRSA in emergency
      department patients.
AB  - Conventional culture methods to detect methicillin-resistant Staphylococcus
      aureus (MRSA) take a few days, and their sensitivity and usefulness also need to
      be improved. In this study, active screening was performed using the polymerase
      chain reaction (PCR) for colonization with MRSA on admission and follow-up
      surveillance after admission to an emergency department between June 2012 and
      August 2012, and the backgrounds of PCR and/or culture-method-positive patients
      were compared. Among 95 patients, 15 (15.8%) patients were positive for MRSA on
      PCR and/or culture; 6.3% (6/95) of patients were positive on admission, and 9.5%
      (9/95) became positive during the stay after admission. The major primary
      diagnoses in MRSA-positive patients were trauma and cerebrovascular diseases.
      Nine (60%) of 15 patients were MRSA-positive on both PCR and culture, compared
      with three (20%) of 15 who were PCR-positive but culture-negative. The other
      three (20%) of 15 patients were PCR-negative but culture-positive. Furthermore,
      there was a tendency for younger age and shorter stay to be associated with PCR
      positive but culture-negative results. These findings suggest that active
      surveillance with PCR may be highly sensitive and useful for the early diagnosis
      of MRSA colonization to prevent nosocomial transmission from the emergency
      department to the regular inpatient wards of the hospital. 

PMID- 25999748
TI  - Cost-effectiveness of ranibizumab versus aflibercept in the treatment of visual
      impairment due to diabetic macular edema: a UK healthcare perspective.
AB  - BACKGROUND: Ranibizumab and aflibercept are alternative anti-vascular endothelial
      growth factor agents approved for the treatment of visual impairment (VI) due to
      diabetic macular edema (DME). OBJECTIVE: To estimate, from a UK healthcare
      perspective, the cost-effectiveness of ranibizumab 0.5 mg pro re nata (PRN) and
      ranibizumab 0.5 mg treat and extend (T&E) compared with aflibercept 2 mg every 8
      weeks after five initial monthly doses (2q8) in the treatment of VI due to DME.
      METHODS: A Markov model previously reviewed by the National Institute for Health
      and Care Excellence was used to simulate the long-term outcomes and costs of
      treating DME. Health states were defined by increments of ten letters in best
      corrected visual acuity (BCVA), with a 3-month cycle length. Patients could gain
      (or lose) a maximum of two health states between cycles. A 3-year treatment time
      frame and a lifetime horizon were used. Future costs and health outcomes were
      discounted at 3.5% per annum. Patient baseline characteristics and the efficacy
      of ranibizumab PRN were derived using data from the RESTORE study. The relative
      efficacies of ranibizumab PRN, ranibizumab T&E, and aflibercept were assessed
      with a network meta-analysis. Different utilities were assigned based on BCVA and
      whether the treated eye was the better- or the worse-seeing eye. Sensitivity
      analyses tested the robustness of the model. RESULTS: Lifetime costs per patient
      of treating DME were L20,019 for ranibizumab PRN, L22,930 for ranibizumab T&E,
      and L25,859 for aflibercept 2q8. Ranibizumab was dominant over aflibercept, with
      an incremental gain of 0.05 quality-adjusted life-years (QALYs) and cost savings
      of L5,841 (PRN) and L2,930 (T&E) compared with aflibercept. Ranibizumab PRN and
      ranibizumab T&E had 79% and 67% probability, respectively, of being cost
      effective relative to aflibercept at a willingness-to-pay threshold of
      L20,000/QALY. When assuming the higher end of PRN injection frequency (15.9 over
      3 years), the cost savings associated with ranibizumab were L3,969. CONCLUSION:
      From a UK healthcare perspective, ranibizumab provides greater health gains with
      lower overall costs than aflibercept in patients with VI due to DME.

PMID- 25999749
TI  - Nab-paclitaxel, docetaxel, or solvent-based paclitaxel in metastatic breast
      cancer: a cost-utility analysis from a Chinese health care perspective.
AB  - BACKGROUND: Paclitaxel and docetaxel are commonly used for metastatic breast
      cancer in the People's Republic of China. To improve the safety and efficacy of
      paclitaxel, an albumin-bound formulation (nab) is now available in the People's
      Republic of China (Abraxane((r))). To provide health economic data for the key
      stakeholders, a cost-utility analysis comparing nab-paclitaxel to docetaxel, both
      as alternatives to paclitaxel, was conducted. METHODS: A meta-analysis of
      clinical outcomes Phase III trials comparing nab-paclitaxel (260 mg/m(2) every
      [q] 3 weeks) or branded docetaxel (100 mg/m(2) q 3 weeks), to solvent-based
      branded paclitaxel (175 mg/m(2) q 3 weeks) was undertaken to provide safety and
      clinical data. Resource use data for the delivery of anticancer therapy and for
      the treatment of grade 3/4 toxicity was collected from a time and motion study
      conducted in three Chinese cancer centers and from a survey of clinicians. Using
      the Time Trade-Off technique, health utility estimates were derived from
      interviewing 28 breast cancer patients from one cancer center in the People's
      Republic of China. All costs were reported in 2014 US dollars. RESULTS: Nab
      paclitaxel had the most favorable safety profile, characterized with the lowest
      incidence of grade 3/4 neutropenia, febrile neutropenia, anemia, and stomatitis.
      When the median number of cycles delivered from the clinical trials was applied,
      nab-paclitaxel had a cost per course of $19,752 compared with $8,940 and $13,741
      for paclitaxel and docetaxel, respectively. As an alternative to paclitaxel, the
      cost per quality-adjusted life-year (QALY) gained with nab-paclitaxel suggested
      better value than with docetaxel ($57,900 vs $130,600). CONCLUSION: Nab
      paclitaxel appears to be a cost-effective option compared with docetaxel and
      paclitaxel, for metastatic breast cancer in the People's Republic of China.

PMID- 25999750
TI  - Application of a validated algorithm to estimate the effectiveness and cost of
      biologics for rheumatoid arthritis in the US pharmacy benefit manager context.
AB  - BACKGROUND: Several biologic medicines are available to treat rheumatoid
      arthritis (RA), and they differ in administration method (subcutaneous or
      intravenous [IV]). We analyzed a pharmacy benefit manager database to estimate
      claims-based, algorithm-determined effectiveness and cost per effectively treated
      patient for biologics used to treat RA. METHODS: We analyzed the Medco Health
      Solutions pharmacy benefit manager database to identify patients with one or more
      claims for a biologic used to treat RA from 2007 to 2012. The first observed
      claim defined the index date, the previous 180 days were the pre-index period,
      and follow-up was 365 days after the index date. Effectiveness of a biologic was
      determined by a validated, published algorithm designed for use in claims
      database analyses. Cost per effectively treated patient as determined by the
      algorithm was calculated as the total annual cost of the biologic therapy divided
      by the number of effectively treated patients. Analyses were conducted for
      subcutaneous, IV, and individual biologics. RESULTS: The analysis population was
      1,090 patients (subcutaneous: 785, IV: 305; etanercept: 440, adalimumab: 345,
      infliximab: 201, abatacept: 104). The mean age was 49.7+/-9.4 years, and 78% of
      the patients were female. Effectiveness according to the algorithm was higher in
      subcutaneous (36%) versus IV biologics (23%; P<0.001), and in etanercept (36%)
      versus infliximab (22%; P<0.001) and versus abatacept (24%; P=0.02). Etanercept
      and adalimumab were similar (35%; P=0.77). The cost per effectively treated
      patient according to the algorithm was $64,738 for subcutaneous biologics,
      $80,408 for IV biologics, $62,841 for etanercept, $67,226 for adalimumab, $90,696
      for infliximab, and $62,303 for abatacept. CONCLUSION: Effectiveness according to
      a validated, claims-based algorithm was higher in subcutaneous versus IV
      biologics. Cost per effectively treated patient according to the algorithm was
      approximately $16,000 less in subcutaneous versus IV biologics.

PMID- 25999751
TI  - Interaction between leucine and phosphodiesterase 5 inhibition in modulating
      insulin sensitivity and lipid metabolism.
AB  - PURPOSE: Leucine activates SIRT1/AMP-activated protein kinase (AMPK) signaling
      and markedly potentiates the effects of other sirtuin and AMPK activators on
      insulin signaling and lipid metabolism. Phosphodiesterase 5 inhibition increases
      nitric oxide-cGMP signaling, which in turn exhibits a positive feedback loop with
      both SIRT1 and AMPK, thus amplifying peroxisome proliferator-activated receptor
      gamma co-activator alpha (PGC1alpha)-mediated effects. METHODS: We evaluated
      potential synergy between leucine and PDE5i on insulin sensitivity and lipid
      metabolism in vitro and in diet-induced obese (DIO) mice. RESULTS: Leucine (0.5
      mM) exhibited significant synergy with subtherapeutic doses (0.1-10 nM) of PDE5
      inhibitors (sildenafil and icariin) on fat oxidation, nitric oxide production,
      and mitochondrial biogenesis in hepatocytes, adipocytes, and myotubes. Effects on
      insulin sensitivity, glycemic control, and lipid metabolism were then assessed in
      DIO-mice. DIO-mice exhibited fasting and postprandial hyperglycemia, insulin
      resistance, and hepatic steatosis, which were not affected by the addition of
      leucine (24 g/kg diet). However, the combination of leucine and a subtherapeutic
      dose of icariin (25 mg/kg diet) for 6 weeks reduced fasting glucose (38%,
      P<0.002), insulin (37%, P<0.05), area under the glucose tolerance curve (20%,
      P<0.01), and fully restored glucose response to exogenous insulin challenge. The
      combination also inhibited hepatic lipogenesis, stimulated hepatic and muscle
      fatty acid oxidation, suppressed hepatic inflammation, and reversed high-fat diet
      induced steatosis. CONCLUSION: These robust improvements in insulin sensitivity,
      glycemic control, and lipid metabolism indicate therapeutic potential for leucine
      PDE5 inhibitor combinations.

PMID- 25999752
TI  - Acne treatment patterns, expectations, and satisfaction among adult females of
      different races/ethnicities.
AB  - BACKGROUND: Limited data are available on acne treatment patterns, expectations,
      and satisfaction in the adult female subpopulation, particularly among different
      racial and ethnic groups. OBJECTIVE: Describe acne treatment patterns and
      expectations in adult females of different racial/ethnic groups and analyze and
      explore their potential effects on medication compliance and treatment
      satisfaction. METHODS: A cross-sectional, Web-based survey was administered to US
      females (25-45 years) with facial acne (>=25 visible lesions). Data collected
      included sociodemographics, self-reported clinical characteristics, acne
      treatment use, and treatment expectations and satisfaction. RESULTS: Three
      hundred twelve subjects completed the survey (mean age, 35.3+/-5.9 years),
      comprising black (30.8%), Hispanic (17.6%), Asian/other (17.3%), and white
      (34.3%). More than half of the subjects in each racial group recently used an
      acne treatment or procedure (black, 63.5%; Hispanic, 54.5%; Asian/other, 66.7%;
      white, 66.4%). Treatment use was predominantly over-the-counter (OTC) (47.4%)
      versus prescription medications (16.6%). OTC use was highest in white subjects
      (black, 42.7%; Hispanic, 34.5%; Asian/other, 44.4%; white, 59.8%; P<0.05). The
      most frequently used OTC treatments in all racial/ethnic groups were salicylic
      acid (SA) (34.3%) and benzoyl peroxide (BP) (32.1%). Overall, compliance with
      acne medications was highest in white versus black (57.0+/-32.4 vs 42.7+/-33.5
      days, P>0.05), Hispanic (57.0+/-32.4 vs 43.2+/-32.9 days, P>0.05), and
      Asian/other (57.0+/-32.4 vs 46.9+/-37.2 days, P>0.05) subjects. Most subjects
      expected OTC (73.7%) and prescription (74.7%) treatments to work quickly. Fewer
      than half of the subjects were satisfied with OTC treatment (BP, 47.0%; SA,
      43.0%), often due to skin dryness (BP, 26.3%; SA, 44.3%) and flakiness (BP,
      12.3%; SA, 31.1%). No statistically significant differences were observed among
      racial/ethnic groups in their level of satisfaction with OTC or prescription acne
      treatments. CONCLUSION: Racial/ethnic differences were observed in acne treatment
      patterns in adult females, while treatment expectations were similar. Results
      indicate that treatment patterns and expectations may impact treatment
      satisfaction and medication compliance.

PMID- 25999753
TI  - The diagnosis and treatment of dermatitis herpetiformis.
AB  - Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with a chronic
      relapsing course, pruritic polymorphic lesions, and typical histopathological and
      immunopathological findings. According to several evidences, DH is considered the
      specific cutaneous manifestation of celiac disease, and the most recent
      guidelines of celiac disease have stated that, in celiac patients with a proven
      DH, a duodenal biopsy is unnecessary for the diagnosis. In this review, the most
      recent data about the diagnosis and the management of DH have been reported and
      discussed. In particular, in patients with clinical and/or histopathological
      findings suggestive for DH, the finding of granular IgA deposits along the dermal
      epidermal junction or at the papillary tips by direct immunofluorescence (DIF)
      assay, together with positive results for anti-tissue transglutaminase antibody
      testing, allows the diagnosis. Thereafter, a gluten-free diet should be started
      in association with drugs, such as dapsone, that are able to control the skin
      manifestations during the first phases of the diet. In conclusion, although DH is
      a rare autoimmune disease with specific immunopathological alterations at the
      skin level, its importance goes beyond the skin itself and may have a big impact
      on the general health status and the quality of life of the patients. 

PMID- 25999755
TI  - Decade-long trends (1999-2009) in the characteristics, management, and hospital
      outcomes of patients hospitalized with acute myocardial infarction with prior
      diabetes and chronic kidney disease.
AB  - BACKGROUND: Despite the increasing magnitude and impact, there are limited data
      available on the clinical management and in-hospital outcomes of patients who
      have diabetes mellitus (DM) and chronic kidney disease (CKD) at the time of
      hospitalization for acute myocardial infarction (AMI). The objectives of our
      population-based observational study in residents of central Massachusetts were
      to describe decade-long trends (1999-2009) in the characteristics, in-hospital
      management, and hospital outcomes of AMI patients with and without these
      comorbidities. METHODS: We reviewed the medical records of 6,018 persons who were
      hospitalized for AMI on a biennial basis between 1999 and 2009 at all eleven
      medical centers in central Massachusetts. Our sample consisted of the following
      four groups: DM with CKD (n=587), CKD without DM (n=524), DM without CKD
      (n=1,442), and non-DM/non-CKD (n=3,465). RESULTS: Diabetic patients with CKD were
      more likely to have a higher prevalence of previously diagnosed comorbidities, to
      have developed heart failure acutely, and to have a longer hospital stay compared
      with non-DM/non-CKD patients. Between 1999 and 2009, there were marked increases
      in the prescribing of beta-blockers, statins, and aspirin for patients with CKD
      and DM as compared to those without these comorbidities. In-hospital death rates
      remained unchanged in patients with DM and CKD, while they declined markedly in
      patients with CKD without DM (20.2% dying in 1999; 11.3% dying in 2009).
      CONCLUSION: Despite increases in the prescribing of effective cardiac
      medications, AMI patients with DM and CKD continue to experience high in-hospital
      death rates.

PMID- 25999756
TI  - Evaluation of the impact of rehospitalization in the management of hepatic
      encephalopathy.
AB  - BACKGROUND: Overt hepatic encephalopathy (HE), which is associated with
      neuropsychiatric symptoms and neuromuscular dysfunction in patients with liver
      cirrhosis, is often managed in the hospital setting. Approximately 60% of
      eligible patients do not receive prophylactic therapy after an overt HE episode.
      OBJECTIVE: The aim of this review is to evaluate the impact of rehospitalization
      on costs and clinical outcomes in HE. METHODS: A PubMed search of English
      language articles through July 9, 2014 was conducted, and bibliographies of
      identified publications were reviewed. Abstracts from relevant professional
      society meetings from 2010 to 2014 were searched. The selected references and
      abstracts reported on the prevalence, costs, or clinical consequences of
      rehospitalization in adults with HE. DATA SYNTHESIS: HE is a key reason for
      readmission among patients hospitalized for complications of cirrhosis. Almost
      40% of patients previously hospitalized for HE may be readmitted within 1 year
      for HE-related reasons. Furthermore, in-hospital US mortality for patients
      admitted for HE is about 7% to 15%. Recurrent HE and hospitalization for
      cirrhosis complications are associated with impaired quality of life. In
      addition, recurrences (especially those requiring hospitalization) may contribute
      to persistent cognitive deficits (eg, impairments in reaction time, attention,
      and working memory) after resolution of an acute episode of overt HE. CONCLUSION:
      The economic and clinical consequences of rehospitalization for patients with
      overt HE underscore the importance of secondary prevention and highlight the need
      to identify reasons for the undertreatment of patients after hospitalization for
      overt HE.

PMID- 25999754
TI  - The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations,
      modifier genes, and diagnosis.
AB  - X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene
      encoding a peroxisomal ABC transporter. In this review, we compare estimates of
      incidence derived from different populations in order to provide an overview of
      the worldwide incidence of X-ALD. X-ALD presents with heterogeneous phenotypes
      ranging from adrenomyeloneuropathy (AMN) to inflammatory demyelinating cerebral
      ALD (CALD). A large number of different mutations has been described, providing a
      unique opportunity for analysis of functional domains within ABC transporters.
      Yet the molecular basis for the heterogeneity of clinical symptoms is still
      largely unresolved, as no correlation between genotype and phenotype exists in X
      ALD. Beyond ABCD1, environmental triggers and other genetic factors have been
      suggested as modifiers of the disease course. Here, we summarize the findings of
      numerous reports that aimed at identifying modifier genes in X-ALD and discuss
      potential problems and future approaches to address this issue. Different options
      for prenatal diagnosis are summarized, and potential pitfalls when applying next
      generation sequencing approaches are discussed. Recently, the measurement of very
      long-chain fatty acids in lysophosphatidylcholine for the identification of
      peroxisomal disorders was included in newborn screening programs. 

PMID- 25999757
TI  - Management of rheumatoid arthritis in People's Republic of China - focus on
      tocilizumab and patient considerations.
AB  - The prevalence of rheumatoid arthritis (RA) is 0.19%-0.41% in Chinese population.
      RA exerts profound influence on health-related quality of life (HRQoL), which
      imposed huge burdens on patients physically, mentally, and economically. As a
      developing country, People's Republic of China faces enormous challenges in
      management of RA. Conventional-synthesized disease-modifying antirheumatic drugs
      (csDMARDs) remain the most selective therapeutic options for RA in People's
      Republic of China owing to their affordable price and fair efficacy as well as
      tolerability. Unfortunately, there are substantial RA patients who are poor
      responders to csDMARDs, even to subsequently combined therapy with tumor necrosis
      factor antagonist (anti-TNF). Tocilizumab (TCZ) has been approved as a subsequent
      line biological agent in patients with moderate-to-severe RA worldwide including
      People's Republic of China. TCZ is the first biological agent approved for the
      treatment of RA inhibiting interlukin-6 (IL-6) by blocking both membrane-bound
      and soluble IL-6 receptors. Open-label studies in real-life practice and strictly
      controlled clinical trials demonstrated its high efficacy and safety profile in
      treatment of patients with RA who have inadequate responses to csDMARDs and anti
      TNF. HRQoL of RA patients was improved in various measurements. TCZ was
      associated with 1.2 times the risk of adverse events, such as infections,
      dyslipidemia, and hepatic transaminases elevation, compared with pooled placebo.
      A relatively long half-life allowing for monthly intravenous administration and a
      newly developed subcutaneous injection make TCZ more acceptable. However, data
      are not enough so far comparing TCZ to anti-TNF. Lack of evidence in Chinese
      patients and high cost of TCZ limit its prescription in People's Republic of
      China being a developing country. Further clinical trials and post-marketing
      surveillance may offer a comprehensive assessment of patient satisfaction and
      acceptability, which may help us define the optimal role for TCZ in therapeutic
      strategy. 

PMID- 25999759
TI  - Ultrasound-guided epidural anesthesia for a parturient with severe malformations
      of the skeletal system undergoing cesarean delivery: a case report.
AB  - Anesthetic management of patients with preexisting diseases is challenging and
      individualized approaches need to be determined based on patients' complications.
      We report here a case of ultrasound-guided epidural anesthesia in combination
      with low-dose ketamine during cesarean delivery on a parturient with severe
      malformations of the skeletal system and airway problems. The ultrasound-guided
      epidural anesthesia was performed in the L1-L2 space, followed by an intravenous
      administration of ketamine (0.5 mg/kg) for sedation and analgesia. Satisfactory
      anesthesia was provided to the patient and spontaneous ventilation was maintained
      during the surgery. The mother and the baby were discharged 5 days after surgery,
      no complications were reported for either of them. Our work demonstrated that an
      ultrasound-guided epidural anesthesia combined with low-dose ketamine can be used
      to successfully maintain spontaneous ventilation and provide effective analgesia
      during surgery and reduce the risk of postoperative anesthesia-related pulmonary
      infection. 

PMID- 25999758
TI  - Necrotizing fasciitis: epidemiology and clinical predictors for amputation.
AB  - BACKGROUND: Necrotizing fasciitis, a relatively uncommon infection involving the
      skin, subcutaneous tissue, and fascia, is a rapidly progressive soft tissue
      infection and a medical and surgical urgency. Delayed debridement, with
      subsequent huge soft tissue loss is associated with loss of limb and infection
      and is the most common cause of mortality. The purpose of this work is to
      describe the epidemiology of necrotizing fasciitis and to identify the clinical
      characteristics that may be used to predict amputation in routine clinical
      practice. METHODS: Retrospective cohort study data were collected from three
      general hospitals located in the Chiang Rai, Kamphaeng Phet, and Phayao provinces
      in northern Thailand. Epidemiologic data for all patients with a surgically
      confirmed diagnosis of necrotizing fasciitis between 2009 and 2012 were
      collected. Medical records and reviews were retrieved from inpatient records,
      laboratory reports, and registers. Clinical predictors for amputation were
      analyzed by multivariable risk regression. RESULTS: A total of 1,507 patients
      with a diagnosis of necrotizing fasciitis were classified as being with
      amputation (n=127, 8.4%) and without amputation (n=1,380, 91.6%). The most common
      causative Gram-positive and Gram-negative pathogens were Streptococcus pyogenes
      (33.3% in the amputation group and 40.8% in the non-amputation group) and
      Escherichia coli (25% in the amputation group and 17.1% in the non-amputation
      group). Predictive factors for amputation included gangrene (risk ratio [RR]
      4.77, 95% confidence interval [CI] 2.70-8.44), diabetes mellitus (RR 3.08, 95% CI
      1.98-4.78), skin necrosis (RR 2.83, 95% CI 2.52-3.18), soft tissue swelling (RR
      1.76, 95% CI 1.24-2.49), and serum creatinine values >=1.6 mg/dL on admission (RR
      1.71, 95% CI 1.38-2.12). All data were analyzed using the multivariable risk
      regression generalized linear model. CONCLUSION: The most causative pathogens
      were S. pyogenes and E. coli. Clinical predictors for amputation in patients with
      necrotizing fasciitis included having diabetes mellitus, soft tissue swelling,
      skin necrosis, gangrene, and serum creatinine values >=1.6 mg/dL on admission.
      Thus, patients with any of these predictors should be monitored closely for
      progression and receive early aggressive treatment to avoid limb loss.

PMID- 25999760
TI  - Blockade of the mental nerve for lower lip surgery as a safe alternative to
      general anesthesia in two very old patients.
AB  - PURPOSE: Regional anesthesia is gaining popularity with anesthesiologists as it
      offers superb postoperative analgesia. However, as the sole anesthetic technique
      in high-risk patients in whom general anesthesia is not preferred, some regional
      anesthetic possibilities may be easily overlooked. By presenting two cases of
      very old patients with considerable comorbidities, we would like to bring the
      mental nerve field block under renewed attention as a safe alternative to general
      anesthesia and to achieve broader application of this simple nerve block.
      PATIENTS AND METHODS: Two very old male patients (84 and 91 years) both presented
      with an ulcerative lesion at the lower lip for which surgical removal was
      scheduled. Because of their considerable comorbidities and increased frailty,
      bilateral blockade of the mental nerve was considered superior to general
      anesthesia. As an additional advantage for the 84-year-old patient, who had a
      pneumonectomy in his medical history, the procedure could be safely performed in
      a beach-chair position to prevent atelectasis and optimize the
      ventilation/perfusion ratio of the single lung. The mental nerve blockades were
      performed intraorally in a blind fashion, after eversion of the lip and
      identifying the lower canine. A 5 mL syringe with a 23-gauge needle attached was
      passed into the buccal mucosa until it approximated the mental foramen, where 2
      mL of lidocaine 2% with adrenaline 1:100.000 was injected. The other side was
      anesthetized in a similar fashion. RESULTS: Both patients underwent the surgical
      procedure uneventfully under a bilateral mental nerve block and were discharged
      from the hospital on the same day. CONCLUSION: A mental nerve block is an easy-to
      perform regional anesthetic technique for lower lip surgery. This technique might
      be especially advantageous in the very old, frail patient.

PMID- 25999762
TI  - Determinant factors of tobacco use among ever-married men in Bangladesh.
AB  - BACKGROUND: The burden of tobacco use is shifting from developed to developing
      countries. This study aimed to explore the different types of tobacco use, and to
      identify the determinant factors associated with the tobacco use among ever
      married men in Bangladesh. DATA AND METHODS: Data of 3,771 ever-married men, 15
      54 years of age were extracted from the Bangladesh Demographic and Health Survey
      2007. Prevalence rate, chi-square (chi(2)) test, and binary logistic regression
      analysis were used as the statistical tools to analyze the data. RESULTS: Tobacco
      use through smoking (58.68%) was found to be higher than that of chewing (21.63%)
      among men, which was significantly more prevalent among the poorest, less
      educated, and businessmen. In bivariate analysis, all the socioeconomic factors
      were found significantly associated with tobacco use; while in multivariate
      analysis, age, education, wealth index, and occupation were identified as the
      significant predictors. CONCLUSION: Tobacco use was found to be remarkably common
      among males in Bangladesh. The high prevalence of tobacco use suggests that there
      is an urgent need for developing intervention plans to address this major public
      health problem in Bangladesh.

PMID- 25999761
TI  - Expanding role of lenalidomide in hematologic malignancies.
AB  - Lenalidomide is an immunomodulatory agent that has been approved by the US Food
      and Drug Administration for treatment of multiple myeloma, deletion 5q
      myelodysplastic syndrome, and mantle cell lymphoma. In addition, it has clinical
      activity in lymphoproliferative disorders and acute myeloid leukemia. The mode of
      action includes immunomodulatory, anti-inflammatory, antiangiogenic, and
      antiproliferative mechanisms. The antitumor effect is a result of direct
      interference of key pathways in tumor cells and indirect modulation of the tumor
      microenvironment. There has been no recent collective review on lenalidomide in
      multiple myeloma, myelodysplastic syndrome/acute myeloid leukemia, and lymphoma.
      This review summarizes the results of current clinical studies of lenalidomide,
      alone and in combination with other agents, as a therapeutic option for various
      hematologic malignancies. 

PMID- 25999763
TI  - Magnitude of opportunistic infections and associated factors in HIV-infected
      adults on antiretroviral therapy in eastern Ethiopia.
AB  - PURPOSE: The aim of this study was to assess the prevalence of opportunistic
      infections (OIs) and associated factors among HIV-infected adults on anti
      retroviral therapy (ART) in Hiwot Fana Specialized University Hospital, Eastern
      Ethiopia. PATIENTS AND METHODS: A hospital-based retrospective study was
      conducted in 358 HIV-infected adult patients on ART from April to June 2014. Data
      were collected through review of clinical records. The data was entered and
      analyzed by using SPSS version 16.0. Univariate and multivariate analyses were
      performed to determine the association of each independent variable with
      occurrence of OIs. A 95% confidence interval (CI) and P-value less than 0.05 were
      considered as significant association. RESULTS: A total of 358 patients were
      included in the study, in which majority (68.4%) were females. The mean age of
      patients was 34 (standard deviation [SD] +/-9.8) years. The overall of prevalence
      of OIs among HIV/AIDS patients on ART was 48%. The highest prevalent rates of OIs
      observed were tuberculosis (TB) (21.23%), followed by Herpes zoster (11.2%) and
      oral candidiasis (9.5%). Baseline CD4 cell count <200 cells/mm(3) (adjusted odds
      ratio [AOR] =1.645, 95% CI =2.187, 3.983), baseline World Health Organization
      (WHO) clinical stage III (AOR =2.801, 95% CI =1.958, 7.165) and IV (AOR =3.856;
      95% CI =2.691, 10.390), and not using prophylaxis (AOR =1.912, 95% CI =1.444,
      3.824) were found to have strong association with acquisition of OIs. CONCLUSION:
      There was a high prevalence of OIs observed in this study. Baselines CD4 count of
      <200 cells/mm(3), advanced WHO clinical stages, and not using prophylaxis were
      found to be predictors of OIs. Interventions were aimed at promoting early HIV
      testing and enrollment of HIV-infected individuals into ART services needed
      before CD4 count decreased severely.

PMID- 25999764
TI  - Dyslipidemia and cardiovascular disease risk profiles of patients attending an
      HIV treatment clinic in Harare, Zimbabwe.
AB  - The chronic inflammation induced by human immunodeficiency virus (HIV)
      contributes to increased risk of coronary heart disease (CHD) in HIV-infected
      individuals. HIV-infected patients generally benefit from being treated with
      antiretroviral drugs, but some antiretroviral agents have side effects, such as
      dyslipidemia and hyperglycemia. There is general consensus that antiretroviral
      drugs induce a long-term risk of CHD, although the levels of that risk are
      somewhat controversial. The intention of this cross-sectional study was to
      describe the lipid profile and the long-term risk of CHD among HIV-positive
      outpatients at an HIV treatment clinic in Harare, Zimbabwe. Two hundred and
      fifteen patients were investigated (females n=165, mean age 39.8 years; males
      n=50; mean age 42.0 years). Thirty of the individuals were antiretroviral-naive
      and 185 had been on antiretroviral therapy (ART) for a mean 3.9+/-3.4 years. All
      participants had average lipid and glucose values within normal ranges, but there
      was a small difference between the ART and ART-for total cholesterol (TC) and
      high-density lipoprotein (HDL). Those on a combination of D4T or ZDV/NVP/3TC and
      PI-based ART were on average oldest and had the highest TC levels. Framingham
      risk showed 1.4% prevalence of high CHD risk within the next ten years. After
      univariate analysis age, sex, TC/HDL ratio, HDL, economic earnings and systolic
      BP were associated with medium to high risk of CHD. After multivariate regression
      analysis and adjusting for age or sex only age, sex and economic earnings were
      associated with medium to high risk of CHD. There is small risk of developing
      CHD, during the next decade in HIV infected patients at an HIV treatment clinic
      in Harare. 

PMID- 25999765
TI  - Cervical cancer screening and treatment of cervical intraepithelial neoplasia in
      female sex workers using "screen and treat" approach.
AB  - OBJECTIVE: Female sex workers (FSWs) are at an increased risk of human
      immunodeficiency virus (HIV) as well as human papillomavirus (HPV) infections and
      thus have an increased risk of cervical intraepithelial neoplasia (CIN) and
      cervical cancer. We evaluated the feasibility of "screen and treat approach" for
      cervical cancer prevention and the performance of different screening tests among
      FSWs. METHODS: Women were screened using cytology, VIA (visual inspection with
      acetic acid), and VILI (visual inspection with Lugol's iodine) and underwent
      colposcopy, biopsy, and immediate treatment using cold coagulation, if indicated,
      at the same visit. RESULTS: We screened 300 FSWs of whom 200 (66.67%) were HIV
      uninfected and 100 (33.34%) were HIV infected. The overall prevalence of CIN 2-3
      lesions was 4.7%. But all women with CIN 2-3 lesions were HIV infected, and thus
      the prevalence of CIN 2-3 lesions in HIV-infected FSWs was 14/100 (14%, 95%
      confidence interval: 7.2-20.8). All of them screened positive by all three
      screening tests. Cold coagulation was well tolerated, with no appreciable side
      effects. CONCLUSION: Cervical cancer prevention by "screen and treat" approach
      using VIA, followed by ablative treatment, in this high-risk group of women is
      feasible and can be implemented through various targeted intervention programs.

PMID- 25999766
TI  - Knowledge and attitudes of Latin American gynecologists regarding unplanned
      pregnancy and use of combined oral contraceptives.
AB  - BACKGROUND: Unintended pregnancy is a public health problem and unmet medical
      need worldwide. It is estimated that in the year 2012, almost 213 million
      pregnancies occurred, and the global pregnancy rate decreased only slightly from
      2008 to 2012. It was also estimated that 85 million pregnancies (40% of all
      pregnancies) were unintended and that 38% ended in an unintended birth.
      OBJECTIVES: To assess knowledge and attitudes of Latin American (LA)
      obstetricians and gynecologists (OBGYNs) regarding unintended pregnancies and
      aspects of combined oral contraceptive (COC) use. METHODS: A survey was conducted
      during a scientific meeting about contraception in 2014, in which OBGYNs from 12
      LA countries who provide attention in contraception were invited to respond to a
      multiple-choice questionnaire to assess their knowledge and attitudes regarding
      unplanned pregnancy and some aspects regarding COC use. RESULTS: A total of 210
      OBGYNs participated in the study. Their knowledge regarding COC failure was low.
      The participants reported they believed that their patients habitually forgot to
      take a pill and that their patients did not know what to do in these situations.
      They were aware of the benefits of COC use; however, they were less prone to
      prescribe COCs for the purpose of protecting against ovarian and endometrial
      cancer, and one-quarter of them had doubts about the association between COC use
      and cancer risk. CONCLUSION: The interviewed LA OBGYNs showed some flaws in terms
      of knowledge of COC failure rates and the non-contraceptive benefits and risks of
      COCs. To adequately counsel their patients regarding COC intake, OBGYNs must be
      updated regarding all aspects of COC use.

PMID- 25999768
TI  - Transfundal puncture of a large ovarian cyst with hysteroscopic and
      ultrasonographic guidance.
AB  - This paper describes the case of an 83-year-old patient with hypertension,
      diabetes, obesity (body mass index - 38), congestive heart failure, and history
      of cardiac surgery, who was referred for a diagnostic-therapeutic decompression
      of a large, symptomatic ovarian cyst. Due to anatomical conditions, the only safe
      way was a transfundal puncture under mini-hysteroscopic and ultrasound guidance.
      A puncture with aspiration of 300 mL of serous fluid from the cyst was performed
      without technical problems and complications. Cytology showed no cancer cells in
      the examined liquid. Relief from pain and compression discomfort was achieved in
      the patient. This case shows the possibility of combining ultrasound and
      minimally invasive diagnostic methods like hysteroscopy in selected clinical
      situations. 

PMID- 25999767
TI  - Relationship power, communication, and violence among couples: results of a
      cluster-randomized HIV prevention study in a South African township.
AB  - BACKGROUND: Inequitable gender-based power in relationships and intimate partner
      violence contribute to persistently high rates of HIV infection among South
      African women. We examined the effects of two group-based HIV prevention
      interventions that engaged men and their female partners together in a couples
      intervention (Couples Health CoOp [CHC]) and a gender-separate intervention
      (Men's Health CoOp/Women's Health CoOp [MHC/WHC]) on women's reports of power,
      communication, and conflict in relationships. METHODS: The cluster-randomized
      field experiment included heterosexual couples from a high-density South African
      township in which neighborhoods were randomized to one of the intervention arms
      or a control arm that received the WHC only. Participants completed in-person
      study visits at baseline and 6-month follow-up. We examined group differences
      using one-way analysis of variance and multivariable regression models. RESULTS:
      Of the 290 couples enrolled, 255 women remained in the same partnership over 6
      months. Following the intervention, women in the CHC arm compared with those in
      the WHC arm were more likely to report an increase in relationship control
      (beta=0.92, 95% confidence interval [CI]: 0.02, 1.83, P=0.045) and gender norms
      supporting female autonomy in relationships (beta=0.99, 95% CI: 0.07, 1.91,
      P=0.035). Women in the MHC/WHC arm were more likely to report increases in
      relationship equity, relative to those in the CHC arm, and had a higher odds of
      reporting no victimization during the previous 3 months (MHC/WHC vs WHC: odds
      ratio =3.05, 95% CI: 1.55, 6.0, P=0.001; CHC vs MHC/WHC: odds ratio =0.38, 95%
      CI: 0.20, 0.74, P=0.004). CONCLUSION: Male partner engagement in either the
      gender-separate or couples-based interventions led to modest improvements in
      gender power, adoption of more egalitarian gender norms, and reductions in
      relationship conflict for females. The aspects of relationship power that
      improved, however, varied between the couples and gender-separate conditions,
      highlighting the need for further attention to development of both gender
      separate and couples interventions.

PMID- 25999769
TI  - A 10-year appraisal of cesarean delivery and the associated fetal and maternal
      outcomes at a teaching hospital in southeast Nigeria.
AB  - BACKGROUND: The global rise in cesarean delivery rate has been a major source of
      public health concern. AIM: To appraise the cesarean deliveries and the
      associated fetal and maternal outcomes. MATERIALS AND METHODS: The study was a
      case series with data collected retrospectively from the records of patients
      delivered by cesarean section at the Ebonyi State University Teaching Hospital,
      Abakaliki over a 10-year period, from January 2002 to December 2011. Ethical
      approval was obtained. RESULTS: Of 14,198 deliveries, 2,323/14,198 (16.4%) were
      by cesarean deliveries. The overall increase of cesarean delivery was 11.1/10
      (1.1%) per annum from 184/1,512 (12.2%) in 2002 to 230/986 (23.3%) in 2011. Of
      2,097 case folders studied, 1,742/2,097 (83.1%) were delivered at term, and in
      1,576/2,097 (75.2%), the cesarean deliveries were emergencies. The common
      indications for cesarean delivery were previous cesarean scars 417/2,097 (19.9%)
      and obstructed labor 331/2,097 (15.8%). There were 296 perinatal deaths, giving a
      perinatal mortality rate of (296/2,197) 134.7/1,000 births. Also, 129/2,097
      (6.1%) maternal case fatalities occurred, giving a maternal mortality rate of
      908.6/100,000 total births. Hemorrhage 57/129 (44.2%) and sepsis 41/129 (32.6%)
      were the major causes. CONCLUSION: The study recorded a significant increase in
      cesarean delivery rate. Previous cesarean scars and obstructed labors were the
      main indications. Perinatal and maternal case fatalities were huge. Hence, there
      is need for continued community education for its reduction.

PMID- 25999770
TI  - An unusual case of prostate tuberculosis: a case report.
AB  - INTRODUCTION: Tuberculosis of the prostate is a rare complication of miliary
      tuberculosis. CASE PRESENTATION: We report a 32-year-old Iranian male diagnosed
      with a case of miliary tuberculosis affecting the prostate. The patient was
      admitted to the hospital with convulsions. Computerized tomography increased the
      clinical suspicion of miliary tuberculosis extending to the prostate where a
      trans-rectal urethral biopsy was obtained. The biopsy revealed multiple
      necrotizing granulomata suggestive of tuberculosis. CONCLUSION: A strong clinical
      suspicion and availability of sophisticated tests with confirmation by biopsy,
      polymerase chain reaction, and culture are needed in order to avoid misdiagnosis
      of complicated miliary tuberculosis cases.

PMID- 25999771
TI  - Effectiveness of a tailored neck training program on neck strength, movement, and
      fatigue in under-19 male rugby players: a randomized controlled pilot study.
AB  - PURPOSE: To investigate the effect of a tailored neck muscle conditioning program
      on neck muscle strength, neck muscle fatigue, and range of neck movement in 16-18
      year-old male rugby players. MATERIALS AND METHODS: Thirty-four male rugby
      players were divided into forward and back playing positions and randomized
      within these groups. Seventeen players were randomly assigned to each group. The
      test group was given a tailored 6-week exercise regime based on their baseline
      measurements to be performed three times a week in addition to their normal
      training and playing. The control group trained and played as normal. The outcome
      measures used were cervical spine range of movement, neck strength, and neck
      muscle fatigability. RESULTS: There were no clinically relevant statistically
      significant differences between the two groups. Trends identified between the two
      groups suggest that a tailored neck exercise program increases neck strength,
      particularly neck extension, and increases resistance to fatigue, as well as
      influencing right- and left-sided neck muscle balance. A reduction in range of
      movement was also demonstrated in the test group. There was a great deal of
      variability in range of movement and strength within this age group. No
      previously undiagnosed neck conditions were detected, and there were no adverse
      events reported. CONCLUSION: This study has shown that neck strength, range of
      movement, and susceptibility of the neck muscles to fatigue can be influenced
      using a focused neck training regime. It forms an important basis for a larger,
      multicenter study to ensure the neck is given due attention in rugby training and
      receives the same focus of conditioning as other parts of the body.

PMID- 25999772
TI  - White coat hypertension: improving the patient-health care practitioner
      relationship.
AB  - White coat hypertension is characterized by the variability of a patient's blood
      pressure measurements between the physician's office and the patient's home
      environment. A patient with white coat hypertension has high blood pressure
      levels in the physician's office and normal blood pressure levels in their
      typical environment. This condition is likely caused by the patient's anxiety
      within the physician's office and in the presence of the physician. Research has
      shown that improving the relationship between a patient and their health care
      provider can decrease the patient's anxiety, with the implication of decreasing
      the patient's likelihood of demonstrating white coat hypertension. This review
      provides an overview of the previous literature regarding white coat
      hypertension, its prevalence, and the consequences for those who develop
      persistent hypertension. Furthermore, this review discusses the implications of
      improving patient and health care provider interactions through effective
      communication, empathy, and trust, as well as the implications for future
      research studies in improving the patient and health care provider's
      relationship. 

PMID- 25999773
TI  - The neutrophil to lymphocyte ratio is associated with severity of rheumatic
      mitral valve stenosis.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is a serious health concern in
      developing countries. Rheumatic mitral stenosis (RMS) is the most long-term
      sequel in RHD. The neutrophil to lymphocyte ratio (NLR) is a novel marker, and a
      higher NLR has been associated with poor clinical outcomes in various
      cardiovascular disorders. We evaluated the availability of NLR to predict
      severity of mitral stenosis (MS) in patients with RHD. METHODS: We analyzed 300
      consecutive patients with RMS. The patients were divided into tertiles according
      to NLR: 0.85< NLR <=1.85 (n=100, tertile 1), 1.86<= NLR <=2.46 (n=100, tertile
      2), and 2.47<= NLR <=7.08 (n=100, tertile 3). Patients with RMS were divided into
      three groups based on the degree of MS as mild, moderate, and severe MS. After
      the initial evaluation, 187 patients with moderate-to-severe RMS (Group 1) and
      113 patients with mild RMS (Group 2) were reassessed. RESULTS: The patients with
      severe RMS had significantly elevated NLR, mean platelet volume, and pulmonary
      artery systolic pressure values compared to patients with moderate and mild MS
      (P<0.001, P<0.001, P<0.001 respectively). Multivariate binary logistic regression
      analysis revealed that high levels of NLR was an independent predictor of severe
      RMS (odds ratio =0.68, P=0.008). Moderate-to-severe RMS incidence was
      significantly higher among patients in the tertile 3 (odds ratio =2.8, P=0.001).
      CONCLUSION: NLR is a new inflammatory marker and a simple, rapid, and easily
      accessible prognostic parameter that can be associated with severity of RMS in
      patients with RHD.

PMID- 25999774
TI  - Adolescents with personality disorders suffer from severe psychiatric stigma:
      evidence from a sample of 131 patients.
AB  - BACKGROUND: The aim of the study is to assess the severity of psychiatric stigma
      in a sample of personality disordered adolescents in order to evaluate whether
      differences in stigma can be found in adolescents with different types and
      severity of personality disorders (PDs). Not only adults but children and
      adolescents with mental health problems suffer from psychiatric stigma. In
      contrast to the abundance of research in adult psychiatric samples, stigma in
      children and adolescents has hardly been investigated. Personality disordered
      adolescents with fragile identities and self-esteem might be especially prone to
      feeling stigmatized, an experience which might further shape their identity
      throughout this critical developmental phase. MATERIALS AND METHODS: One hundred
      thirty-one adolescent patients underwent a standard assessment with Axis I and
      Axis II diagnostic interviews and two stigma instruments, Stigma Consciousness
      Questionnaire (SCQ) and Perceived Devaluation-Discrimination Questionnaire
      (PDDQ). Independent sample t-tests were used to investigate differences in the
      mean SCQ and PDDQ total scores for patients with and without a PD. Multiple
      regression main effect analyses were conducted to explore the impact of the
      different PDs on level of stigma, as well as comorbid Axis I disorders. Age and
      sex were also entered in the regression models. RESULTS AND CONCLUSIONS:
      Adolescents with severe mental health problems experience a burden of stigma.
      Personality disordered patients experience more stigma than adolescents with
      other severe psychiatric Axis I disorders. Borderline PD is the strongest
      predictor of experiences of stigma. More severely personality disordered
      adolescents tend to experience the highest level of stigma.

PMID- 25999775
TI  - Limitations of the biopsychosocial model in psychiatry.
AB  - A commitment to an integrative, non-reductionist clinical and theoretical
      perspective in medicine that honors the importance of all relevant domains of
      knowledge, not just "the biological," is clearly evident in Engel's original
      writings on the biopsychosocial model. And though this model's influence on
      modern psychiatry (in clinical as well as educational settings) has been
      significant, a growing body of recent literature is critical of it - charging it
      with lacking philosophical coherence, insensitivity to patients' subjective
      experience, being unfaithful to the general systems theory that Engel claimed it
      be rooted in, and engendering an undisciplined eclecticism that provides no
      safeguards against either the dominance or the under-representation of any one of
      the three domains of bio, psycho, or social. 

PMID- 25999776
TI  - A self-paced oral feeding system that enhances preterm infants' oral feeding
      skills.
AB  - AIM: Very low birth weight (VLBW) infants have difficulty transitioning to
      independent oral feeding, be they breast- or bottle-feeding. We developed a 'self
      paced' feeding system that eliminates the natural presence of the positive
      hydrostatic pressure and internal vacuum build-up within a bottle during feeding.
      Such system enhanced these infants' oral feeding performance as monitored by
      overall transfer (OT; % ml taken/ml prescribed), rate of transfer (RT; ml/min
      over an entire feeding). This study hypothesizes that the improvements observed
      in these infants resulted from their ability to use more mature oral feeding
      skills (OFS). METHODS: 'Feeders and growers' born between 26-29 weeks gestation
      were assigned to a control or experimental group fed with a standard or self
      paced bottle, respectively. They were monitored when taking 1-2 and 6-8 oral
      feedings/day. OFS was monitored using our recently published non-invasive
      assessment scale that identifies 4 maturity levels based on infants' RT and
      proficiency (PRO; % ml taken during the first 5 min of a feeding/total ml
      prescribed) during bottle feeding. RESULTS: Infants oral feeding outcomes, i.e.,
      OT, RT, PRO, and OFS maturity levels were enhanced in infants fed with the self
      paced vs. standard bottle (p <= 0.007). CONCLUSION: The improved oral feeding
      performance of VLBW infants correlated with enhanced OFS. This study is a first
      to recognize that VLBW infants' true OFS are more mature than recognized. We
      speculate that the physical properties inherent to standard bottles that are
      eliminated with the self-paced system interfere with the display of their true
      oral feeding potential thereby hindering their overall oral feeding performance.

PMID- 25999777
TI  - Organisational reporting and learning systems: Innovating inside and outside of
      the box.
AB  - Reporting and learning systems are key organisational tools for the management
      and prevention of clinical risk. However, current approaches, such as incident
      reporting, are struggling to meet expectations of turning health systems like the
      UK National Health Service (NHS) into learning organisations. This article aims
      to open up debate on the potential for novel reporting and learning systems in
      healthcare, by reflecting on experiences from two recent projects: Proactive Risk
      Monitoring in Healthcare (PRIMO) and Errordiary in Healthcare. These two
      approaches demonstrate how paying attention to ordinary, everyday clinical work
      can derive useful learning and active discussion about clinical risk. We argue
      that innovations in reporting and learning systems might come from both inside
      and outside of the box. 'Inside' being along traditional paths of controlled
      organisational innovation. 'Outside' in the sense that inspiration comes outside
      of the healthcare domain, or more extremely, outside official channels through
      external websites and social media (e.g. patient forums, public review sites,
      whistleblower blogs and Twitter streams). Reporting routes that bypass official
      channels could empower staff and patient activism, and turn out to be a driver to
      challenge organisational processes, assumptions and priorities where the
      organisation is failing and has become unresponsive.

PMID- 25999778
TI  - God put a thought into my mind: the charismatic Christian experience of receiving
      communications from God.
AB  - The agentive aspects of communicative religious experiences remain somewhat
      neglected in the social sciences literature. There is a need for phenomenological
      descriptions of these experiences and the ways in which they differ from
      culturally defined psychopathological states. In this semi-structured interview
      study, eight congregants attending an evangelical church in London were asked to
      describe their experiences of God communicating with them. Communications from
      God were related to current events rather than to the prediction of future
      events. These communications were received as thoughts and do not generally
      reveal metaphysical insights, but rather they relate to the mundane world. They
      provided direction, consolation and empowerment in the lives of those receiving
      them. Individuals recounted that on occasion God sometimes speaks audibly, or
      accompanied by supernatural phenomena, but in the vast majority of cases, the way
      God speaks is through thoughts or impressions. In all instances, agency is
      maintained, individuals can choose to obey the thoughts/voices or not. The
      findings are discussed in relation to externalisation of agency and the
      phenomenon of thought insertion in schizophrenia.

PMID- 25999779
TI  - Association mapping and genomic prediction for resistance to sudden death
      syndrome in early maturing soybean germplasm.
AB  - Sudden death syndrome (SDS), caused by Fusarium virguliforme, has spread to
      northern soybean growing regions in the US causing significant yield losses. The
      objectives of this study were to identify loci underlying variation in plant
      responses to SDS through association mapping (AM) and to assess prediction
      accuracy of genomic selection (GS) in a panel of early maturing soybean
      germplasm. A set of 282 soybean breeding lines was selected from the University
      of Minnesota soybean breeding program and then genotyped using a genome-wide
      panel of 1536 single-nucleotide polymorphism markers. Four resistance traits,
      root lesion severity (RLS), foliar symptom severity (FSS), root retention (RR),
      and dry matter reduction (DMR), were evaluated using soil inoculation in the
      greenhouse. AM identified significant peaks in genomic regions of known SDS
      resistance quantitative trait loci cqSDS001, cqRfs4, and SDS11-2. Additionally,
      two novel loci, one on chromosome 3 and another on chromosome 18, were
      tentatively identified. A ninefold cross-validation scheme was used to assess the
      prediction accuracy of GS for SDS resistance. The prediction accuracy of single
      trait GS (ST-GS) was 0.64 for RLS, but less than 0.30 for RR, DMR, and FSS.
      Compared to ST-GS, none of multi-trait GS (MT-GS) models significantly improved
      the prediction accuracy due to weak correlations between the four traits. This
      study suggests both AM and GS hold promise for implementation in genetic
      improvement of SDS resistance in existing soybean breeding programs.

PMID- 25999780
TI  - Niche segregation in two closely related species of stickleback along a
      physiological axis: explaining multidecadal changes in fish distribution from
      iron-induced respiratory impairment.
AB  - Acute exposure to iron can be lethal to fish, but long-term sublethal impacts of
      iron require further study. Here we investigated whether the spatial and temporal
      distribution (1967-2004) of two closely related species of stickleback matched
      the spatial distribution of iron concentrations in the groundwater. We used the
      'Northern Peel region', a historically iron-rich peat landscape in The
      Netherlands as a case study. This allowed us to test the hypothesis that niche
      segregation in two closely related species of stickleback occurred along a
      physiological axis. Patterns in stickleback occurrence were strongly associated
      with spatial patterns in iron concentrations before 1979: iron-rich grid cells
      were avoided by three-spined stickleback (Gasterosteus aculeatus, Linnaeus 1758)
      and preferred by nine-spined stickleback (Pungitius pungitius, [Linnaeus, 1758]).
      After 1979, the separation between both sticklebacks became weaker, corresponding
      to a decreased influence of local groundwater on stream water quality. The way
      both species changed their distribution in the field provides a strong indication
      that they differ in their susceptibility to iron-rich conditions. These observed
      differences correspond with differences in their respiration physiology,
      tolerance of poor oxygen conditions and overall life-history strategy documented
      in the literature. Our results exemplify how species can partition niche along a
      non-structural niche axis, such as sublethal iron-rich conditions. Other fish
      species may similarly segregate along concentration gradients in iron, while
      sublethal concentrations of other metals such as copper may similarly impact fish
      via respiratory impairment and reduced aerobic scope.

PMID- 25999781
TI  - Complex investigations of structural and thermal properties of silica-titania
      adsorbents.
AB  - Mesoporous titanium-containing silicas with different Titania contents were
      investigated. The structural parameters of the materials were characterized by
      low-temperature adsorption/desorption of nitrogen and X-ray diffraction analysis.
      The thermodesorption of water using the quasi-isothermal thermogravimetry as well
      as the differential scanning calorimetry were used to characterize thermal and
      surface properties of these materials. The adsorbed water layers and the
      concentration of weakly and strongly bound water as well as the surface free
      energy on the adsorbent/water interfaces were calculated. It was stated that the
      increase of Titania content causes a gradual decrease of specific surface area
      and formation of biporous structure inside the tested materials. The water
      thermodesorption from the surface proceeds in two or three stages, which is
      connected mainly with pore distribution and TiO2 content. One can observe the
      increase of the total surface free energy (DeltaGSigma) with the increasing TiO2
      content, but the largest DeltaGSigma value at the adsorbent/strongly bound water
      interface is exhibited by the adsorbent of intermediate content (30%) of TiO2.
      Freezing temperature of water contained in the pores of the studied materials is
      connected largely with their porous structure. Due to the well developed porous
      structure, the water freezing process is a multi-stage one.

PMID- 25999782
TI  - An integrative top-down and bottom-up qualitative model construction framework
      for exploration of biochemical systems.
AB  - Computational modelling of biochemical systems based on top-down and bottom-up
      approaches has been well studied over the last decade. In this research, after
      illustrating how to generate atomic components by a set of given reactants and
      two user pre-defined component patterns, we propose an integrative top-down and
      bottom-up modelling approach for stepwise qualitative exploration of interactions
      among reactants in biochemical systems. Evolution strategy is applied to the top
      down modelling approach to compose models, and simulated annealing is employed in
      the bottom-up modelling approach to explore potential interactions based on
      models constructed from the top-down modelling process. Both the top-down and
      bottom-up approaches support stepwise modular addition or subtraction for the
      model evolution. Experimental results indicate that our modelling approach is
      feasible to learn the relationships among biochemical reactants qualitatively. In
      addition, hidden reactants of the target biochemical system can be obtained by
      generating complex reactants in corresponding composed models. Moreover,
      qualitatively learned models with inferred reactants and alternative topologies
      can be used for further web-lab experimental investigations by biologists of
      interest, which may result in a better understanding of the system.

PMID- 25999784
TI  - Locating and applying sociological theories of risk-taking to develop public
      health interventions for adolescents.
AB  - Sociological theories seldom inform public health interventions at the community
      level. The reasons for this are unclear but may include difficulties in finding,
      understanding or operationalising theories. We conducted a study to explore the
      feasibility of locating sociological theories within a specific field of public
      health, adolescent risk-taking, and to consider their potential for practical
      application. We identified a range of sociological theories. These explained risk
      taking: (i) as being due to lack of social integration; (ii) as a consequence of
      isolation from mainstream society; (iii) as a rite of passage; (iv) as a response
      to social constraints; (v) as resistance; (vi) as an aspect of adolescent
      development; (vii) by the theory of the 'habitus'; (viii) by situated rationality
      and social action theories; and (ix) as social practice. We consider these
      theories in terms of their potential to inform public health interventions for
      young people.

PMID- 25999785
TI  - The promyelocytic leukemia protein is upregulated in conditions of obesity and
      liver steatosis.

PMID- 25999786
TI  - The Xanthine Derivative KMUP-1 Attenuates Serotonin-Induced Vasoconstriction and
      K+-Channel Inhibitory Activity via the PKC Pathway in Pulmonary Arteries.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a potent pulmonary vasoconstrictor that
      promotes pulmonary artery smooth muscle cell (PASMC) proliferation. 5-HT-induced
      K(+) channel inhibition increases [Ca(2+)]i in PASMCs, which is a major trigger
      for pulmonary vasoconstriction and development of pulmonary arterial hypertension
      (PAH). This study investigated whether KMUP-1 reduces pulmonary vasoconstriction
      in isolated pulmonary arteries (PAs) and attenuates 5-HT-inhibited K(+) channel
      activities in PASMCs. In endothelium-denuded PA rings, KMUP-1 (1 MUM) dose
      dependently reduced 5-HT (100 MUM) mediated contractile responses. Responses to
      KMUP-1 were reversed by K(+) channel inhibitors (TEA, 10 mM, 4-aminopyridine, 5
      mM, and paxilline, 10 MUM). In primary PASMCs, KMUP-1 also dose-dependently
      restored 5-HT-inhibited voltage-gated K(+)-channel (Kv1.5 and Kv2.1) and large
      conductance Ca(2+)-activated K(+)-channel (BKCa) proteins, as confirmed by
      immunofluorescent staining. Furthermore, 5-HT (10 MUM)-inhibited Kv1.5 protein
      was unaffected by the PKA inhibitor KT5720 (1 MUM) and the PKC activator PMA (1
      MUM), but these effects were reversed by KMUP-1 (1 MUM), 8-Br-cAMP (100 MUM),
      chelerythrine (1 MUM), and KMUP-1 combined with a PKA/PKC activator or inhibitor.
      Notably, KMUP-1 reversed 5-HT-inhibited Kv1.5 protein and this response was
      significantly attenuated by co-incubation with the PKC activator PMA, suggesting
      that 5-HT-mediated PKC signaling can be modulated by KMUP-1. In conclusion, KMUP
      1 ameliorates 5-HT-induced vasoconstriction and K(+)-channel inhibition through
      the PKC pathway, which could be valuable to prevent the development of PAH. 

PMID- 25999787
TI  - Garlic Oil Suppressed Nitrosodiethylamine-Induced Hepatocarcinoma in Rats by
      Inhibiting PI3K-AKT-NF-kappaB Pathway.
AB  - To explore the underlying mechanisms for the protective effects of garlic oil
      (GO) against nitrosodiethylamine (NDEA)-induced hepatocarcinoma, 60 male Wistar
      rats were randomized into 4 groups (n=15): control group, NDEA group, and two GO
      plus NDEA groups. The rats in GO plus NDEA groups were pretreated with GO (20 or
      40 mg/kg) for 7 days. Then, all rats except those in control group were gavaged
      with NDEA for 20 weeks, and the rats in GO plus NDEA groups were continuously
      administered with GO. The results showed that GO co-treatment significantly
      suppressed the NDEA-induced increases of alpha fetal protein (AFP) level in
      serum, nuclear atypia in H&E staining, sirius red-positive areas and
      proliferating cell nuclear antigen (PCNA) expression. The molecular mechanisms
      exploration revealed that the protein levels of phosphatidylinositol 3 kinase
      (PI3K)-p85, PI3K-p110, total AKT, p-AKT (Ser473) and p-AKT (Thr308) in the liver
      of NDEA group rats were higher than those in control group rats. In addition,
      NDEA treatment induced IkappaB degradation and NF-kappaB p65 phosphorylation, and
      up-regulated the protein levels of downstream pro-inflammatory mediators. GO co
      treatment significantly reversed all the above adverse effects induced by NDEA.
      These results suggested that the protective effects of GO against NDEA-induced
      hepatocarcinoma might be associated with the suppression of PI3K- AKT-NF-kappaB
      pathway. 

PMID- 25999788
TI  - Role of the renin-angiotensin system, renal sympathetic nerve system, and
      oxidative stress in chronic foot shock-induced hypertension in rats.
AB  - OBJECTIVE: The renin-angiotensin system (RAS) and renal sympathetic nerve system
      (RSNS) are involved in the development of hypertension. The present study is
      designed to explore the possible roles of the RAS and the RSNS in foot shock
      induced hypertension. METHODS: Male Sprague-Dawley rats were divided into six
      groups: control, foot shock, RSNS denervation, denervation plus foot shock,
      Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot
      shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received
      foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive
      substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma,
      the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px),
      and renal noradrenaline content. RAS component mRNA and protein levels were
      quantified in the cerebral cortex and hypothalamus. RESULTS: The two week foot
      shock treatment significantly increased systolic blood pressure, which was
      accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and
      protein expression in the cerebral cortex and hypothalamus, an increase of the
      plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a
      decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase
      was suppressed by denervation of the RSNS or treatment with Captopril or Tempol.
      Interestingly, denervation or Tempol treatment both decreased main RAS components
      not only in the circulatory system, but also in the central nervous system. In
      addition, decreased antioxidant levels and increased TBARS and corticosterone
      levels were also partially restored by denervation or treatment with Tempol or
      Captopril. CONCLUSIONS: RAS, RSNS and oxidative stress reciprocally potentiate to
      play important roles in the development of foot shock-induced hypertension.

PMID- 25999789
TI  - A Novel Role of OS-9 in the Maintenance of Intestinal Barrier Function from
      Hypoxia-induced Injury via p38-dependent Pathway.
AB  - OS-9 is a lectin required for efficient ubquitination of glycosylated substrates
      of endoplasmic reticulum-associated degradation (ERAD). OS-9 has previously been
      implicated in ER-to-Golgi transport and transcription factor turnover. However,
      we know very little about other functions of OS-9 under endoplasmic reticulum
      stress. Here, we used gene knockdown and overexpression approaches to study the
      protective effect of OS-9 on intestinal barrier function of intestinal epithelial
      cell Caco-2 monolayer. We found that OS-9 attenuated intestinal epithelial
      barrier dysfunction under hypoxia through up-regulating occludin and claudin-1
      protein expression. Furthermore, we showed that the up-regulation of occludin and
      claudin-1 induced by OS-9 was mediated by p38 and ERK1/2 phosphorylation and did
      not involve HIF-1alpha. In summary, our results demonstrate that OS-9 up
      regulates occludin and claudin-1 by activating the MAP kinase (MAPK) pathway, and
      thus protects the epithelial barrier function of Caco-2 monolayer under hypoxia
      condition. 

PMID- 25999790
TI  - Functions of autophagy in pathological cardiac hypertrophy.
AB  - Pathological cardiac hypertrophy is the response of heart to various
      biomechanical and physiopathological stimuli, such as aging, myocardial ischemia
      and hypertension. However, a long-term exposure to the stress makes heart
      progress to heart failure. Autophagy is a dynamic self-degradative process
      necessary for the maintenance of cellular homeostasis. Accumulating evidence has
      revealed a tight link between cardiomyocyte autophagy and cardiac hypertrophy.
      Sophisticatedly regulated autophagy protects heart from various physiological and
      pathological stimuli by degradating and recycling of protein aggregates, lipid
      drops, or organelles. Here we review the recent progresses concerning the
      functions of autophagy in cardiac hypertrophy induced by various hypertrophic
      stimuli. Moreover, the therapeutic strategies targeting autophagy for cardiac
      hypertrophy will also be discussed. 

PMID- 25999791
TI  - P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes
      Intestinal Tumorigenesis in Apc(Min/+) Mice.
AB  - Studies have indicated that platelets play an important role in tumorigenesis,
      and an abundance of platelets accumulate in the ovarian tumor microenvironment
      outside the vasculature. However, whether cancer cells recruit platelets within
      intestinal tumors and how they signal adherent platelets to enter intestinal
      tumor tissues remain unknown. Here, we unexpectedly found that large numbers of
      platelets were deposited within human colorectal tumor specimens using
      immunohistochemical staining, and these platelets were fully associated with
      tumor development. We further report the robust adhesion of platelet aggregates
      to tumor cells within intestinal tumors, which occurs via a mechanism that is
      dependent on P-selectin (CD62P), a cell adhesion molecule that is abundantly
      expressed on activated platelets. Using spontaneous intestinal tumor mouse
      models, we determined that the genetic deletion of P-selectin suppressed
      intestinal tumor growth, which was rescued by the infusion of wild-type platelets
      but not P-selectin(-/-) platelets. Mechanistically, platelet adhesion to tumor
      cells induced the secretion of vascular endothelial growth factor (VEGF) to
      promote angiogenesis and accelerate intestinal tumor cell proliferation. Our
      results indicate that the adherence of platelets to tumor cells could promote
      tumor growth and metastasis. By targeting this platelet-tumor cell interaction,
      recombinant soluble P-selectin may have therapeutic value for the treatment of
      intestinal tumors. 

PMID- 25999793
TI  - HOXB5 Promotes the Proliferation and Invasion of Breast Cancer Cells.
AB  - HOX transcription factors play an important role in determining body patterning
      and cell fate during embryogenesis. Accumulating evidence has shown that these
      genes act as positive and/or negative modulators in many types of cancer,
      including breast cancer, in a tissue-specific manner. We have previously reported
      that HOXB5 is aberrantly overexpressed in breast cancer tissues and cell lines.
      Here, we investigated the biological roles and clinical relevance of HOXB5 in
      breast cancer. Immunohistochemical analysis of HOXB5 on tissue microarray (TMA)
      including 34 normal and 67 breast cancer specimens revealed that HOXB5 was highly
      expressed in cancer tissues, particularly from estrogen receptor (ER)-positive
      breast cancer patients. An online survival analysis confirmed the correlation
      between HOXB5 expression and poor distant metastasis-free survival in ER
      positive, but not in ER-negative, breast cancer. In vitro studies indicated that
      HOXB5 silencing in ER-positive cells significantly decreased cell proliferation
      and anchorage-independent cell growth. In contrast, overexpression of HOXB5
      displayed EMT characteristics with a greater invasive ability, higher cell
      proliferation and colony formation in soft agar. HOXB5 knockdown or
      overexpression led to changes in the expression levels of RET, ERBB2, and EGFR,
      but not of ESR1. In conclusion, we suggest that HOXB5 acts as a positive
      modulator most likely by promoting cell proliferative response and invasiveness
      in ER-positive breast cancer. These results would help predict prognosis of
      breast cancer and identify a new valuable therapeutic target. 

PMID- 25999792
TI  - Zebrafish Lbh-like Is Required for Otx2-mediated Photoreceptor Differentiation.
AB  - The homeobox transcription factor orthodenticle homolog 2 (otx2) is supposed as
      an organizer that orchestrates a transcription factor network during
      photoreceptor development. However, its regulation in the process remains
      unclear. In this study, we have identified a zebrafish limb bud and heart-like
      gene (lbh-like), which is expressed initially at 30 hours post fertilization
      (hpf) in the developing brain and eyes. Lbh-like knockdown by morpholinos
      specifically inhibits expression of multiple photoreceptor-specific genes, such
      as opsins, gnat1, gnat2 and irbp. Interestingly, otx2 expression in the morphants
      is not significantly reduced until 32 hpf when lbh-like begins to express, but
      its expression level in 72 hpf morphants is higher than that in wild type
      embryos. Co-injection of otx2 and its downstream target neuroD mRNAs can rescue
      the faults in eyes of Lbh-like morphants. Combined with the results of promoter
      reporter assay, we suggest that lbh-like is a new regulator of photoreceptor
      differentiation directly through affecting otx2 expression in zebrafish.
      Furthermore, knockdown of lbh-like increases the activity of Notch pathway and
      perturbs the balance among proliferation, differentiation and survival of
      photoreceptor precursors. 

PMID- 25999795
TI  - Registered nurses' experiences of patient violence on acute care psychiatric
      inpatient units: an interpretive descriptive study.
AB  - BACKGROUND: Nurses working in acute care psychiatry settings experience high
      rates of patient violence which influences outcomes for nurses and the
      organization. This qualitative study explored psychiatric nurses' experiences of
      patient violence in acute care inpatient psychiatric settings. METHODS: An
      interpretive descriptive design guided this study that included 17 semi
      structured interviews with a purposeful sample of 12 Canadian registered nurses
      who self-reported experiencing patient violence within acute care inpatient
      psychiatry. Thematic analysis and constant comparison techniques were used for
      analysis. A problem, needs and practice analysis was also used to structure
      overall data interpretation. RESULTS: Thirty three unique exposures to patient
      violence among the sample of nurses were analysed. Nurses reported experiencing
      physical, emotional and verbal violence. For many, patient violence was
      considered "part of the job." Nurses often struggled with role conflict between
      one's duty to care and one's duty to self when providing care following a
      critical incident involving violence. Issues of power, control and stigma also
      influenced nurse participant perceptions and their responses to patient violence.
      Nurses used a variety of strategies to maintain their personal safety and to
      prevent, and manage patient violence. Nurses endorsed the need for improved
      education, debriefing following an incident, and a supportive work environment to
      further prevent patient violence. Present findings have implications for reducing
      the barriers to reporting violent experiences and the creation of best practice
      guidelines to reduce patient violence in the workplace. CONCLUSIONS:
      Understanding the perspectives and experiences of nurses in acute inpatient
      psychiatry leads to greater understanding of the phenomenon of patient violence
      and may inform the development of interventions to prevent and to respond to
      patient violence, as well as support nurses working within the acute care
      setting.

PMID- 25999794
TI  - Induction of Phosphoenolpyruvate Carboxykinase (PEPCK) during Acute Acidosis and
      Its Role in Acid Secretion by V-ATPase-Expressing Ionocytes.
AB  - Vacuolar-Type H(+)-ATPase (V-ATPase) takes the central role in pumping H(+)
      through cell membranes of diverse organisms, which is essential for surviving
      acid-base fluctuating lifestyles or environments. In mammals, although glucose is
      believed to be an important energy source to drive V-ATPase, and
      phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme for gluconeogenesis, is
      known to be activated in response to acidosis, the link between acid secretion
      and PEPCK activation remains unclear. In the present study, we used zebrafish
      larva as an in vivo model to show the role of acid-inducible PEPCK activity in
      glucose production to support higher rate of H(+) secretion via V-ATPase, by
      utilizing gene knockdown, glucose supplementation, and non-invasive scanning ion
      selective electrode technique (SIET). Zebrafish larvae increased V-ATPase
      mediated acid secretion and transiently expression of Pck1, a zebrafish homolog
      of PEPCK, in response to acid stress. When pck1 gene was knocked down by specific
      morpholino, the H(+) secretion via V-ATPase decreased, but this effect was
      rescued by supplementation of glucose into the yolk. By assessing changes in
      amino acid content and gene expression of respective enzymes, glutamine and
      glutamate appeared to be the major source for replenishment of Krebs cycle
      intermediates, which are subtracted by Pck1 activity. Unexpectedly, pck1
      knockdown did not affect glutamine/glutamate catalysis, which implies that Pck1
      does not necessarily drive this process. The present study provides the first in
      vivo evidence that acid-induced PEPCK provides glucose for acid-base homeostasis
      at an individual level, which is supported by rapid pumping of H(+) via V-ATPase
      at the cellular level. 

PMID- 25999796
TI  - Pidotimod: the state of art.
AB  - Despite the use of antibiotics and vaccines, the frequency of respiratory tract
      infections is still high and these infections interest a wide range of patients,
      from children to aged people, including in particular these extreme categories
      because of the deficiency of their immune system, due to immaturity in the former
      case and to "immunosenescence" in the latter. For that reason immunostimulant
      drugs are getting more important to prevent and to attenuate infections.
      Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4carboxylic acid) is a synthetic
      dipeptide with immunomodulatory properties. We reviewed studies conducted on
      different categories of patients, with particular attention on children and
      senile patients suffering from recurrent respiratory tract infections,
      associated, or not, with asthma or COPD. The outcomes considered are both
      clinical and laboratory parameters. The common end-point of these studies is that
      Pidotimod has an immunomodulatory activity which is able both to improve the
      clinical conditions of patients and to enhance and stimulate their immunity cells
      (lymphocytes but not only) functions acting on adaptive and innate immunity.
      Pidotimod is also able to increase the concentration of salivary IgA directed
      against bacteria; furthermore, it can modulate airway epithelial cells functions
      up-regulating the expression of toll-like receptors and acting on adhesion
      molecules. According to studies conducted on patients with atopic asthma, it
      seems that Pidotimod could affect T-lymphocytes balance with a possible
      addictional anti-allergic activity. Furthermore, it has been demonstrated an
      improvement of FEV1 and PEF in asthmatic patients treated with Pidotimod. Main
      clinical outcomes are the reduction of the number of infectious episodes, lesser
      severity of signs and symptoms and, consequently, a reduction in use of
      antibiotics and symptomatic drugs, less working and school days lost, less
      mortality and morbidity. The studies considered give positive results, confirming
      Pidotimod's efficacy. Furthermore, many studies show a good safety profile of the
      drug, without recording serious adverse events and mutagenic potential, and a
      very low incidence of side effects. Pidotimod is also a more safe solution in
      patients subjected to vaccination, if compared to lyophilized polibacterial,
      which can't be administered for thirty days before vaccination. 

PMID- 25999797
TI  - Assessing the risk of imminent aggression in institutionalized youth offenders
      using the dynamic appraisal of situational aggression.
AB  - Aggressive behavior in incarcerated youth presents a significant problem for
      staff, co-residents and the functioning of the institution. This study aimed to
      examine the predictive validity of an empirically validated measure, designed to
      appraise the risk of imminent aggression within institutionalized adult
      psychiatric patients (Dynamic Appraisal of Situational Aggression; DASA), in
      adolescent male and female offenders. The supervising staff members on the
      residential units rated the DASA daily for 49 youth (29 males and 20 females)
      over two months. The results showed that DASA total scores significantly
      predicted institutional aggression in the following 24 and 48 hrs; however, the
      predictive validity of the DASA for institutional aggression was, at best,
      modest. Further analyses on male and female subsamples revealed that the DASA
      total scores only predicted imminent institutional aggression in the male
      subsample. Item analyses showed that negative attitudes, anger when requests are
      denied, and unwillingness to follow instructions predicted institutional
      aggression more strongly as compared with other behavioral manifestations of an
      irritable and unstable mental state as assessed by the DASA.

PMID- 25999798
TI  - Antimicrobial Stewardship Programs: Appropriate Measures and Metrics to Study
      their Impact.
AB  - Antimicrobial stewardship is a new field that struggles to find the right balance
      between meaningful and useful metrics to study the impact of antimicrobial
      stewardship programs (ASPs). ASP metrics primarily measure antimicrobial use,
      although microbiological resistance and clinical outcomes are also important
      measures of the impact an ASP has on a hospital and its patient population.
      Antimicrobial measures looking at consumption are the most commonly used
      measures, and are focused on defined daily doses, days of therapy, and costs,
      usually standardized per 1,000 patient-days. Each measure provides slightly
      different information, with their own upsides and downfalls. Point prevalence
      measurement of antimicrobial use is an increasingly used approach to
      understanding consumption that does not entirely rely on sophisticated electronic
      information systems, and is also replicable. Appropriateness measures hold appeal
      and promise, but have not been developed to the degree that makes them useful and
      widely applicable. The primary reason why antimicrobial stewardship is necessary
      is the growth of antimicrobial resistance. Accordingly, antimicrobial resistance
      is an important metric of the impact of an ASP. The most common approach to
      measuring resistance for ASP purposes is to report rates of common or important
      community- or nosocomial-acquired antimicrobial-resistant organisms, such as
      methicillin-resistant Staphylococcus aureus and Clostridium difficile. Such an
      approach is dependent on detection methods, community rates of resistance, and co
      interventions, and therefore may not be the most accurate or reflective measure
      of antimicrobial stewardship interventions. Development of an index to reflect
      the net burden of resistance holds theoretical promise, but has yet to be
      realized. Finally, programs must consider patient outcome measures. Mortality is
      the most objective and reliable method, but has several drawbacks. Disease- or
      organism-specific mortality, or cure, are increasingly used metrics.

PMID- 25999799
TI  - Dengue: Moving from Current Standard of Care to State-of-the-Art Treatment.
AB  - Treatment of dengue remains supportive in the absence of targeted antiviral
      therapy or approved vaccines. Responsive fluid management is key to preventing
      progression to shock or other severe manifestations. The dynamic natural history
      of dengue infection and its influence on hemodynamic homeostasis needs to be
      carefully considered in the planning of individualized therapy. Though largely
      self-limiting, the sheer burden of dengue disease on the global population will
      result in atypical manifestations especially in children, older adults, and
      comorbid patients. Management of these has not yet been systematized. The failure
      of recent randomized controlled trials to show utility for antiviral and
      immunomodulatory agents in dengue is disappointing. Vaccine candidates hold
      promise, but growing outbreaks require more robust, evidence-based management
      guidelines to inform clinicians, especially in novel epidemic situations.

PMID- 25999801
TI  - Effects of Hysterectomy on Sexual Function.
AB  - Hysterectomy remains the most common major gynecological surgery. Postoperative
      sexual function is a concern for many women and their partners. In this respect,
      a beneficial effect of hysterectomy for benign disease independent of surgical
      techniques or removal of the cervix has been demonstrated in the past decade by
      the majority of studies. For about 20 % of women, deteriorated sexual function
      has been reported and current research is attempting to identify mechanisms and
      predictive factors explaining these postoperative changes. Alternative treatments
      of benign uterine disorders or uterus preserving surgery for genital prolapse
      appeared to have similar outcomes in terms of sexual function. Concomitant
      oophorectomy had negative effects on sexual function and long-term health,
      particularly in premenopausal women. This may not be reversed by estrogen
      replacement. Hysterectomy performed for malignancy had a detrimental effect on
      sexual function. Individualized risk assessment and information should be aimed
      at during preoperative decision making.

PMID- 25999800
TI  - Cytomegalovirus Treatment.
AB  - In treating cytomegalovirus (CMV) infection, it is crucial to decide whether one
      is treating pre-emptively or if one is treating established disease. Disease may
      be further divided into viral syndrome and tissue-invasive disease. Generally,
      mild disease in immunosuppressed patients may be treated with oral
      valganciclovir. Treatment may also be started with valganciclovir for CMV
      retinitis in AIDS patients. In other tissue-invasive syndromes, starting with
      intravenous ganciclovir or foscarnet at full doses (adjusted for renal function)
      is preferred. Treatment at full doses should be continued until symptom
      resolution and until blood antigenemia (or DNAemia) is cleared. Patients
      receiving treatment must be closely monitored for side effects to the drugs, as
      well as for response. Drug-resistant CMV is a therapeutic challenge; combination
      therapy with both ganciclovir and foscarnet may be tried. In extreme cases,
      resorting to unconventional agents like leflunomide or maribavir may be
      necessary. Immune reconstitution, through reduction in immunosuppression, or the
      introduction of anti-retroviral therapy, should be attempted. CMX001 is a novel
      agent active against double-stranded viruses; thus far, resistance to CMX001 does
      not confer resistance to ganciclovir or foscarnet. Hence, prophylaxis or pre
      emptive treatment with CMX001 may allow the use of ganciclovir or foscarnet for
      treatment.

PMID- 25999802
TI  - A Review of Testosterone Pellets in the Treatment of Hypogonadism.
AB  - Currently, the most popular form of testosterone replacement is the topical gels
      that require daily applications and incur a risk of transfer of testosterone to
      partners and family. One of the problems with testosterone replacement is the
      short half-life of testosterone. A long-acting formulation is appealing to
      patients and physicians. In 1972, fused crystalline testosterone pellets were
      approved in the USA by the FDA but they were not marketed until 2008.
      Pharmacokinetics studies were available on a different formulation from which
      much can be learned and applied to the current formulation, Testopel(r). The
      decay kinetics, pituitary suppression, and effect on other sex steroids are
      reviewed as well as the short-term complication rates. This review should provide
      the testosterone pellet implanter a better understanding of the physiology of
      testosterone pellet supplementation for hypogonadism.

PMID- 25999803
TI  - Sexual Issues in Treating Trauma Survivors.
AB  - The effect of interpersonal trauma on sexuality can be profound. The field of
      sexual trauma is complex empirically and clinically, with contradictory theories
      and conflicting data. Research definitions and treatment protocols for child
      sexual abuse are very imprecise. There are no firm, empirically proven guidelines
      for treating men and women who have been sexually abused as children or
      adolescents. Overt sexual abuse (OSA) in children and adolescents is defined here
      as molestation, rape, or incest. Research has shown that OSA may, but does not
      necessarily, lead to sexual dysfunction in adulthood. The effects of OSA are
      worsened by concurrent types of family of origin abuse, such as emotional abuse
      or physical abuse. One factor that seems related to the varying impact of OSA on
      adult sexuality is the patients' family of origin experience with nonsexual
      Milestones of Sexual Development. Without positive experiences with touch, trust
      and empathy, the ability to relax and be soothed, and power, the effects of OSA
      are potentiated and complicated. Sexuality is embodied, so experiences with touch
      are particularly important when working with OSA. A three-color Body Map
      technique which assesses stored associations to touch is provided. The concept of
      developmental sexual trauma (DST) is introduced as a way to label traumagenic
      family events which potentiate OSA or negatively effect sex but which are not
      explicitly sexual in origin. Strategies to assess and treat OSA are reviewed.
      Body Maps are recommended to assess and treat sexual trauma.

PMID- 25999804
TI  - All-Atom Internal Coordinate Mechanics (ICM) Force Field for Hexopyranoses and
      Glycoproteins.
AB  - We present an extension of the all-atom internal-coordinate force field, ICMFF,
      that allows for simulation of heterogeneous systems including hexopyranose
      saccharides and glycan chains in addition to proteins. A library of standard
      glycan geometries containing alpha- and beta-anomers of the most common
      hexapyranoses, i.e., d-galactose, d-glucose, d-mannose, d-xylose, l-fucose, N
      acetylglucosamine, N-acetylgalactosamine, sialic, and glucuronic acids, is
      created based on the analysis of the saccharide structures reported in the
      Cambridge Structural Database. The new force field parameters include molecular
      electrostatic potential-derived partial atomic charges and the torsional
      parameters derived from quantum mechanical data for a collection of minimal
      molecular fragments and related molecules. The phi/psi torsional parameters for
      different types of glycosidic linkages are developed using model compounds
      containing the key atoms in the full carbohydrates, i.e., glycosidic-linked
      tetrahydropyran-cyclohexane dimers. Target data for parameter optimization
      include two-dimensional energy surfaces corresponding to the phi/psi glycosidic
      dihedral angles in the disaccharide analogues, as determined by quantum
      mechanical MP2/6-31G** single-point energies on HF/6-31G** optimized structures.
      To achieve better agreement with the observed geometries of glycosidic linkages,
      the bond angles at the O-linkage atoms are added to the internal variable set and
      the corresponding bond bending energy term is parametrized using quantum
      mechanical data. The resulting force field is validated on glycan chains of 1-12
      residues from a set of high-resolution X-ray glycoprotein structures based on
      heavy atom root-mean-square deviations of the lowest-energy glycan conformations
      generated by the biased probability Monte Carlo (BPMC) molecular mechanics
      simulations from the native structures. The appropriate BPMC distributions for
      monosaccharide-monosaccharide and protein-glycan linkages are derived from the
      extensive analysis of conformational properties of glycoprotein structures
      reported in the Protein Data Bank. Use of the BPMC search leads to significant
      improvements in sampling efficiency for glycan simulations. Moreover, good
      agreement with the X-ray glycoprotein structures is achieved for all glycan chain
      lengths. Thus, average/median RMSDs are 0.81/0.68 A for one-residue glycans and
      1.32/1.47 A for three-residue glycans. RMSD from the native structure for the
      lowest-energy conformation of the 12-residue glycan chain (PDB ID 3og2) is 1.53
      A. Additionally, results obtained for free short oligosaccharides using the new
      force field are in line with the available experimental data, i.e., the most
      populated conformations in solution are predicted to be the lowest energy ones.
      The newly developed parameters allow for the accurate modeling of linear and
      branched hexopyranose glycosides in heterogeneous systems.

PMID- 25999805
TI  - Movement and perceptual strategies to intercept virtual sound sources.
AB  - To intercept a moving object, one needs to be in the right place at the right
      time. In order to do this, it is necessary to pick up and use perceptual
      information that specifies the time to arrival of an object at an interception
      point. In the present study, we examined the ability to intercept a laterally
      moving virtual sound object by controlling the displacement of a sliding handle
      and tested whether and how the interaural time difference (ITD) could be the main
      source of perceptual information for successfully intercepting the virtual
      object. The results revealed that in order to accomplish the task, one might need
      to vary the duration of the movement, control the hand velocity and time to reach
      the peak velocity (speed coupling), while the adjustment of movement initiation
      did not facilitate performance. Furthermore, the overall performance was more
      successful when subjects employed a time-to-contact (tau) coupling strategy. This
      result shows that prospective information is available in sound for guiding goal
      directed actions. 

PMID- 25999806
TI  - Axonal activity in vivo: technical considerations and implications for the
      exploration of neural circuits in freely moving animals.
AB  - While extracellular somatic action potentials from freely moving rats have been
      well characterized, axonal activity has not. We have recently reported
      extracellular tetrode recordings of short duration waveforms (SDWs) with an
      average peak-trough duration less than 172 MUs. These waveforms have
      significantly shorter duration than somatic action potentials and tend to be
      triphasic. The present review discusses further data that suggests SDWs are
      representative of axonal activity, how this characterization allows for more
      accurate classification of somatic activity and could serve as a means of
      exploring signal integration in neural circuits. The review also discusses how
      axons may function as more than neural cables and the implications this may have
      for axonal information processing. While the technical challenges necessary for
      the exploration of axonal processes in functional neural circuits during behavior
      are impressive, preliminary evidence suggests that the in vivo study of axons is
      attainable. The resulting theoretical implications for systems level function
      make refinement of this approach a necessary goal toward developing a more
      complete understanding of the processes underlying learning, memory and attention
      as well as the pathological states underlying mental illness and epilepsy. 

PMID- 25999807
TI  - The blood-brain barrier and methamphetamine: open sesame?
AB  - The chemical and electrical microenvironment of neurons within the central
      nervous system is protected and segregated from the circulation by the vascular
      blood-brain barrier. This barrier operates on the level of endothelial cells and
      includes regulatory crosstalk with neighboring pericytes, astrocytes, and
      neurons. Within this neurovascular unit, the endothelial cells form a formidable,
      highly regulated barrier through the presence of inter-endothelial tight
      junctions, the absence of fenestrations, and the almost complete absence of fluid
      phase transcytosis. The potent psychostimulant drug methamphetamine transiently
      opens the vascular blood-brain barrier through either or both the modulation of
      inter-endothelial junctions and the induction of fluid-phase transcytosis. Direct
      action of methamphetamine on the vascular endothelium induces acute opening of
      the blood-brain barrier. In addition, striatal effects of methamphetamine and
      resultant neuroinflammatory signaling can indirectly lead to chronic dysfunction
      of the blood-brain barrier. Breakdown of the blood-brain barrier may exacerbate
      the neuronal damage that occurs during methamphetamine abuse. However, this
      process also constitutes a rare example of agonist-induced breakdown of the blood
      brain barrier and the adjunctive use of methamphetamine may present an
      opportunity to enhance delivery of chemotherapeutic agents to the underlying
      neural tissue. 

PMID- 25999808
TI  - Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar
      in anorexia nervosa and healthy control subjects.
AB  - BACKGROUND: Inconsistent findings about the neurobiology of Anorexia Nervosa (AN)
      hinder the development of effective treatments for this severe mental disorder.
      Therefore, the need arises for elucidation of neurobiological factors involved in
      the pathophysiology of AN. The hypothalamus plays a key role in the
      neurobiological processes that govern food intake and energy homeostasis,
      processes that are disturbed in anorexia nervosa (AN). The present study will
      assess the hypothalamic response to energy intake and the hypothalamic structure
      in patients with AN and healthy controls. METHODS: Ten women aged 18-30 years
      diagnosed with AN and 11 healthy, lean (BMI < 23 kg/m(2)) women in the same age
      range were recruited. We used functional magnetic resonance imaging (MRI) to
      determine function of the hypothalamus in response to glucose. Structural MRI was
      used to determine differences in hypothalamic volume and local gray matter volume
      using manual segmentation and voxel-based morphometry. RESULTS: No differences
      were found in hypothalamic volume and neuronal activity in response to a glucose
      load between the patients and controls. Whole brain structural analysis showed a
      significant decrease in gray matter volume in the cingulate cortex in the AN
      patients, bilaterally. CONCLUSIONS: We argue that in spite of various known
      changes in the hypothalamus the direct hypothalamic response to glucose intake is
      similar in AN patients and healthy controls.

PMID- 25999809
TI  - Functional optical probing of the hippocampal trisynaptic circuit in vitro:
      network dynamics, filter properties, and polysynaptic induction of CA1 LTP.
AB  - Decades of brain research have identified various parallel loops linking the
      hippocampus with neocortical areas, enabling the acquisition of spatial and
      episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal
      cortex layer II -> dentate gyrus (DG) -> cornu ammonis (CA)-3 -> CA1] was studied
      in great detail because of its seemingly simple connectivity and characteristic
      structures that are experimentally well accessible. While numerous researchers
      focused on functional aspects, obtained from a limited number of cells in
      distinct hippocampal subregions, little is known about the neuronal network
      dynamics which drive information across multiple synapses for subsequent long
      term storage. Fast voltage-sensitive dye imaging in vitro allows real-time
      recording of activity patterns in large/meso-scale neuronal networks with high
      spatial resolution. In this way, we recently found that entorhinal theta
      frequency input to the DG most effectively passes filter mechanisms of the
      trisynaptic circuit network, generating activity waves which propagate across the
      entire DG-CA axis. These "trisynaptic circuit waves" involve high-frequency
      firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA
      receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP).
      CA1 LTP has been substantially evidenced to be essential for some forms of
      explicit learning in mammals. Here, we review data with particular reference to
      whole network-level approaches, illustrating how activity propagation can take
      place within the trisynaptic circuit to drive formation of CA1 LTP. 

PMID- 25999810
TI  - Sub-millimeter T2 weighted fMRI at 7 T: comparison of 3D-GRASE and 2D SE-EPI.
AB  - Functional magnetic resonance imaging (fMRI) allows studying human brain function
      non-invasively up to the spatial resolution of cortical columns and layers. Most
      fMRI acquisitions rely on the blood oxygenation level dependent (BOLD) contrast
      employing T(*) 2 weighted 2D multi-slice echo-planar imaging (EPI). At ultra-high
      magnetic field (i.e., 7 T and above), it has been shown experimentally and by
      simulation, that T2 weighted acquisitions yield a signal that is spatially more
      specific to the site of neuronal activity at the cost of functional sensitivity.
      This study compared two T2 weighted imaging sequences, inner-volume 3D Gradient
      and-Spin-Echo (3D-GRASE) and 2D Spin-Echo EPI (SE-EPI), with evaluation of their
      imaging point-spread function (PSF), functional specificity, and functional
      sensitivity at sub-millimeter resolution. Simulations and measurements of the
      imaging PSF revealed that the strongest anisotropic blurring in 3D-GRASE (along
      the second phase-encoding direction) was about 60% higher than the strongest
      anisotropic blurring in 2D SE-EPI (along the phase-encoding direction). In a
      visual paradigm, the BOLD sensitivity of 3D-GRASE was found to be superior due to
      its higher temporal signal-to-noise ratio (tSNR). High resolution cortical depth
      profiles suggested that the contrast mechanisms are similar between the two
      sequences, however, 2D SE-EPI had a higher surface bias owing to the higher T(*)
      2 contribution of the longer in-plane EPI echo-train for full field of view
      compared to the reduced field of view of zoomed 3D-GRASE. 

PMID- 25999812
TI  - phMRI: methodological considerations for mitigating potential confounding
      factors.
AB  - Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional
      MRI that adds pharmacological manipulations in order to study the effects of
      drugs, or uses pharmacological probes to investigate basic or applied (e.g.,
      clinical) neuroscience questions. Issues that may confound the interpretation of
      results from various types of phMRI studies are briefly discussed, and a set of
      methodological strategies that can mitigate these problems are described. These
      include strategies that can be employed at every stage of investigation, from
      study design to interpretation of resulting data, and additional techniques
      suited for use with clinical populations are also featured. Pharmacological MRI
      is a challenging area of research that has both significant advantages and
      formidable difficulties, however with due consideration and use of these
      strategies many of the key obstacles can be overcome. 

PMID- 25999813
TI  - Proteases at work: cues for understanding neural development and degeneration.
AB  - Proteolytical processing of membrane bound molecules is a fundamental mechanism
      for the degradation of these proteins as well as for controlling cell-to-cell
      communication, which is at the basis of tissue development and homeostasis.
      Members of families of metalloproteinases and intra-membrane proteases are major
      effectors of these events. A recent workshop in Baeza, Spain, was devoted to
      discuss how this mechanism coordinates brain development and how its dysfunction
      leads to brain pathologies. Herein we summarize the findings presented during
      this workshop, which illuminate the role of metalloproteinases, including matrix
      metalloproteinase, A Disintegrin and Metalloproteinase-proteases and intra
      membrane proteases, in the regulation of neurogenesis, axon guidance, and
      synaptogenesis as well as in neurodegeneration. Indeed, there is increasing
      evidence that proteolysis at the membrane is directly linked to neuropathologies
      such as Alzheimer Disease and autism spectrum or prion disorders. These
      proteolytic events are tightly regulated and we are just at the beginning of
      understanding how these processes could be exploited to design therapeutic
      treatments aimed at alleviating psychiatric and neurodegenerative pathologies. 

PMID- 25999811
TI  - The neuroenergetics of stress hormones in the hippocampus and implications for
      memory.
AB  - Acute stress causes rapid release of norepinephrine (NE) and glucocorticoids
      (GCs), both of which bind to hippocampal receptors. This release continues, at
      varying concentrations, for several hours following the stressful event, and has
      powerful effects on hippocampally-dependent memory that generally promote
      acquisition and consolidation while impairing retrieval. Several studies have
      characterized the brain's energy usage both at baseline and during memory
      processing, but there are few data on energy requirements of memory processes
      under stressful conditions. Because memory is enhanced by emotional arousal such
      as during stress, it is likely that molecular memory processes under these
      conditions differ from those under non-stressful conditions that do not activate
      the hypothalamic-pituitary-adrenal (HPA) axis. Mobilization of peripheral and
      central energy stores during stress may increase hippocampal glucose metabolism
      that enhances salience and detail to facilitate memory enhancement. Several
      pathways activated by the HPA axis affect neural energy supply and metabolism,
      and may also prevent detrimental damage associated with chronic stress. We
      hypothesize that alterations in hippocampal metabolism during stress are key to
      understanding the effects of stress hormones on hippocampally-dependent memory
      formation. Second, we suggest that the effects of stress on hippocampal
      metabolism are bi-directional: within minutes, NE promotes glucose metabolism,
      while hours into the stress response GCs act to suppress metabolism. These bi
      directional effects of NE and GCs on glucose metabolism may occur at least in
      part through direct modulation of glucose transporter-4. In contrast, chronic
      stress and prolonged elevation of hippocampal GCs cause chronically suppressed
      glucose metabolism, excitotoxicity and subsequent memory deficits. 

PMID- 25999815
TI  - Inhibition of UCH-L1 in oligodendroglial cells results in microtubule
      stabilization and prevents alpha-synuclein aggregate formation by activating the
      autophagic pathway: implications for multiple system atrophy.
AB  - alpha-Synuclein (alpha-syn) positive glial cytoplasmic inclusions (GCI)
      originating in oligodendrocytes (ODC) are a characteristic hallmark in multiple
      system atrophy (MSA). Their occurrence may be linked to a failure of the
      ubiquitin proteasome system (UPS) or the autophagic pathway. For proteasomal
      degradation, proteins need to be covalently modified by ubiquitin, and
      deubiquitinated by deubiquitinating enzymes (DUBs) before proteolytic degradation
      is performed. The DUB ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a
      component of the UPS, it is abundantly expressed in neuronal brain cells and has
      been connected to Parkinson's disease (PD). It interacts with alpha-syn and
      tubulin. The present study was undertaken to investigate whether UCH-L1 is a
      constituent of ODC, the myelin forming cells of the CNS, and is associated with
      GCIs in MSA. Furthermore, LDN-57444 (LDN), a specific UCH-L1 inhibitor, was used
      to analyze its effects on cell morphology, microtubule (MT) organization and the
      proteolytic degradation system. Towards this an oligodendroglial cell line (OLN
      cells), stably transfected with alpha-syn or with alpha-syn and GFP-LC3, to
      monitor the autophagic flux, was used. The data show that UCH-L1 is expressed in
      ODC derived from the brains of newborn rats and colocalizes with alpha-syn in
      GCIs of MSA brain sections. LDN treatment had a direct impact on the MT network
      by affecting tubulin posttranslational modifications, i.e., acetylation and
      tyrosination. An increase in alpha-tubulin detyrosination was observed and
      detyrosinated MT were abundantly recruited to the cellular extensions.
      Furthermore, small alpha-syn aggregates, which are constitutively expressed in
      OLN cells overexpressing alpha-syn, were abolished, and LDN caused the
      upregulation of the autophagic pathway. Our data add to the knowledge that the
      UPS and the autophagy-lysosomal pathway are tightly balanced, and that UCH-L1 and
      its regulation may play a role in neurodegenerative diseases with oligodendroglia
      pathology. 

PMID- 25999814
TI  - The role of the GABA system in amphetamine-type stimulant use disorders.
AB  - Abuse of amphetamine-type stimulants (ATS) has become a global public health
      problem. ATS causes severe neurotoxicity, which could lead to addiction and could
      induce psychotic disorders or cognitive dysfunctions. However, until now, there
      has been a lack of effective medicines for treating ATS-related problems.
      Findings from recent studies indicate that in addition to the traditional
      dopamine-ergic system, the GABA (gamma-aminobutyric acid)-ergic system plays an
      important role in ATS abuse. However, the exact mechanisms of the GABA-ergic
      system in amphetamine-type stimulant use disorders are not fully understood. This
      review discusses the role of the GABA-ergic system in ATS use disorders,
      including ATS induced psychotic disorders and cognitive dysfunctions. We conclude
      that the GABA-ergic system are importantly involved in the development of ATS use
      disorders through multiple pathways, and that therapies or medicines that target
      specific members of the GABA-ergic system may be novel effective interventions
      for the treatment of ATS use disorders. 

PMID- 25999816
TI  - How the Wnt signaling pathway protects from neurodegeneration: the mitochondrial
      scenario.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder and is
      characterized by progressive memory loss and cognitive decline. One of the
      hallmarks of AD is the overproduction of amyloid-beta aggregates that range from
      the toxic soluble oligomer (Abetao) form to extracellular accumulations in the
      brain. Growing evidence indicates that mitochondrial dysfunction is a common
      feature of neurodegenerative diseases and is observed at an early stage in the
      pathogenesis of AD. Reports indicate that mitochondrial structure and function
      are affected by Abetao and can trigger neuronal cell death. Mitochondria are
      highly dynamic organelles, and the balance between their fusion and fission
      processes is essential for neuronal function. Interestingly, in AD, the process
      known as "mitochondrial dynamics" is also impaired by Abetao. On the other hand,
      the activation of the Wnt signaling pathway has an essential role in synaptic
      maintenance and neuronal functions, and its deregulation has also been implicated
      in AD. We have demonstrated that canonical Wnt signaling, through the Wnt3a
      ligand, prevents the permeabilization of mitochondrial membranes through the
      inhibition of the mitochondrial permeability transition pore (mPTP), induced by
      Abetao. In addition, we showed that non-canonical Wnt signaling, through the
      Wnt5a ligand, protects mitochondria from fission-fusion alterations in AD. These
      results suggest new approaches by which different Wnt signaling pathways protect
      neurons in AD, and support the idea that mitochondria have become potential
      therapeutic targets for the treatment of neurodegenerative disorders. Here we
      discuss the neuroprotective role of the canonical and non-canonical Wnt signaling
      pathways in AD and their differential modulation of mitochondrial processes,
      associated with mitochondrial dysfunction and neurodegeneration. 

PMID- 25999818
TI  - Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3'UTR.
AB  - The central nervous system (CNS) monitors modifications in metabolic parameters
      or hormone levels and elicits adaptive responses such as food intake regulation.
      Particularly, within the hypothalamus, leptin modulates the activity of pro
      opiomelanocortin (POMC) neurons which are critical regulators of energy balance.
      Consistent with a pivotal role of the melanocortin system in the control of
      energy homeostasis, disruption of the POMC gene causes hyperphagia and obesity.
      MicroRNAs (miRNAs) are short noncoding RNA molecules that post-transcriptionally
      repress the expression of genes by binding to 3'-untranslated regions (3'UTR) of
      the target mRNAs. However, little is known regarding the role of miRNAs that
      target POMC 3'UTR in the central control energy homeostasis. Particularly, their
      interaction with the leptin signaling pathway remain unclear. First, we used
      common prediction programs to search for potential miRNAs target sites on 3'UTR
      of POMC mRNA. This screening identified a set of conserved miRNAs seed sequences
      for mir-383, mir-384-3p, and mir-488. We observed that mir-383, mir-384-3p, and
      mir-488 are up-regulated in the hypothalamus of leptin deficient ob/ob mice. In
      accordance with these observations, we also showed that mir-383, mir-384-3p, and
      mir-488 were increased in db/db mice that exhibit a non-functional leptin
      receptor. The intraperitoneal injection of leptin down-regulated the expression
      of these miRNAs of interest in the hypothalamus of ob/ob mice showing the
      involvement of leptin in the expression of mir-383, mir-384-3p, and mir-488.
      Finally, the evaluation of responsivity to intracerebroventricular administration
      of leptin exhibited that a chronic treatment with leptin decreased mir-488
      expression in hypothalamus of C57BL/6 mice. In summary, these results suggest
      that leptin modulates the expression of miRNAs that target POMC mRNA in
      hypothalamus. 

PMID- 25999817
TI  - Integrated plasticity at inhibitory and excitatory synapses in the cerebellar
      circuit.
AB  - The way long-term potentiation (LTP) and depression (LTD) are integrated within
      the different synapses of brain neuronal circuits is poorly understood. In order
      to progress beyond the identification of specific molecular mechanisms, a system
      in which multiple forms of plasticity can be correlated with large-scale neural
      processing is required. In this paper we take as an example the cerebellar
      network, in which extensive investigations have revealed LTP and LTD at several
      excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three
      main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar
      nuclei) and correspondingly regulate the function of their three main neurons:
      granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN)
      cells. All these neurons, in addition to be excited, are reached by feed-forward
      and feed-back inhibitory connections, in which LTP and LTD may either operate
      synergistically or homeostatically in order to control information flow through
      the circuit. Although the investigation of individual synaptic plasticities in
      vitro is essential to prove their existence and mechanisms, it is insufficient to
      generate a coherent view of their impact on network functioning in vivo. Recent
      computational models and cell-specific genetic mutations in mice are shedding
      light on how plasticity at multiple excitatory and inhibitory synapses might
      regulate neuronal activities in the cerebellar circuit and contribute to learning
      and memory and behavioral control. 

PMID- 25999819
TI  - CD44: molecular interactions, signaling and functions in the nervous system.
AB  - CD44 is the major surface hyaluronan (HA) receptor implicated in intercellular
      and cell-matrix adhesion, cell migration and signaling. It is a transmembrane,
      highly glycosylated protein with several isoforms resulting from alternative gene
      splicing. The CD44 molecule consists of several domains serving different
      functions: the N-terminal extracellular domain, the stem region, the
      transmembrane domain and the C-terminal tail. In the nervous system, CD44
      expression occurs in both glial and neuronal cells. The role of CD44 in the
      physiology and pathology of the nervous system is not entirely understood,
      however, there exists evidence suggesting it might be involved in the axon
      guidance, cytoplasmic Ca(2+) clearance, dendritic arborization, synaptic
      transmission, epileptogenesis, oligodendrocyte and astrocyte differentiation,
      post-traumatic brain repair and brain tumour development. 

PMID- 25999820
TI  - Development of the adult neurogenic niche in the hippocampus of mice.
AB  - When does adult hippocampal neurogenesis begin? We describe the development of
      the neurogenic niche in the subgranular zone (SGZ) of the hippocampal dentate
      gyrus. We did so from the perspective of the situation in the adult. Ontogeny of
      the dentate gyrus is complex and results in an ectopic neurogenic niche that
      lifelong generates new granule cells. Neurogenesis during the fetal and early
      postnatal periods builds the dentate gyrus and gives way to activity-dependent
      "adult" neurogenesis. We used markers most relevant to adult neurogenesis
      research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2,
      Doublecortin (DCX), NeuroD1 and Prox1. We found that massive changes and a local
      condensation of proliferating precursor cells occurs between postnatal day 7
      (P7), near the peak in proliferation, and P14. Before and around P7, the spatial
      distribution of cells and the co-localization of markers were distinct from the
      situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the
      radial glial marker BLBP were not overlapping during embryonic development,
      presumably indicating different types of radial glia-like cells. Before P7 GFAP
      positive cells in the hilus lacked the radial orientation that is characteristic
      of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3
      progenitor cells and early postmitotic neurons in the adult, showed diffuse
      expression before P7. Intermediate progenitor cell marker Tbr2 became restricted
      to the SGZ but was found in the granule cell layer (GCL) and hilus before.
      Lineage markers NeuroD1 and Prox1 confirmed this pattern. We conclude that the
      neurogenic niche of adult neurogenesis is in place well before true adulthood.
      This might indicate that consistent with the hypothesized function of adult
      neurogenesis in activity-dependent plasticity, the early transition from
      postnatal neurogenesis to adult neurogenesis coincides with the time, when the
      young mice start to become active themselves. 

PMID- 25999821
TI  - Sexual dimorphism of sulcal morphology of the ferret cerebrum revealed by MRI
      based sulcal surface morphometry.
AB  - The present study quantitatively assessed sexual dimorphism of cortical
      convolution and sulcal morphology in young adult ferrets by MRI-based sulcal
      surface morphometry. Ex vivo T1-weighted (short TR/TE) MRI of the ferret cerebrum
      was acquired with high spatial resolution at 7-tesla. The degree of cortical
      convolution, evaluated quantitatively based on 3D MRI data by sulcation index
      (SI), was significantly greater in males (0.553 +/- 0.036) than in females (0.502
      +/- 0.043) (p < 0.001). The rostrocaudal distribution of the cortical convolution
      revealed a greater convolution in the frontal region of the cortex in males than
      in females and by a posterior extension of the convolution in the temporo-parieto
      occipital region of males. Although the cerebral width in the frontal region was
      not different between sexes, the rhinal fissure and rostral region of splenial
      sulcus were more infolded in males than in females. On the contrary, the cerebral
      width was greater in males in the temporo-parieto-occipital region, and male
      prominent posterior extension of infolding was noted in the lateral sulcus,
      caudal suprasylvian sulcus, pesudosylvian sulcus, hippocampal sulcus, and the
      caudal region of splenial sulcus. Notably, the caudal descending region of
      lateral sulcus was clearly infolded in males, but obscured in females. The
      present results suggest a region-related sexual dimorphism of the sulcal
      infolding, which is reflected by local cortical expansion in the ferret cerebrum.
      In particular, male-favored sulcal infolding with expansion of the temporo
      parieto-occipital neocortex may be relevant to the human cerebral cortex
      regarding visuo-spatial and emotion processing, which are known to differ between
      sexes. The present results will provide fundamental information assessing sex
      related changes in the regional sulcal infolding, when ferrets with
      experimentally-induced gyrification abnormality will be used as models for male
      prevalent or male-earlier-onset neurodevelopmental disorders. 

PMID- 25999823
TI  - Design, fabrication, and packaging of an integrated, wirelessly-powered optrode
      array for optogenetics application.
AB  - The recent development of optogenetics has created an increased demand for
      advancing engineering tools for optical modulation of neural circuitry. This
      paper details the design, fabrication, integration, and packaging procedures of a
      wirelessly-powered, light emitting diode (LED) coupled optrode neural interface
      for optogenetic studies. The LED-coupled optrode array employs microscale LED
      (MULED) chips and polymer-based microwaveguides to deliver light into multi-level
      cortical networks, coupled with microelectrodes to record spontaneous changes in
      neural activity. An integrated, implantable, switched-capacitor based stimulator
      (SCS) system provides high instantaneous power to the MULEDs through an inductive
      link to emit sufficient light and evoke neural activities. The presented system
      is mechanically flexible, biocompatible, miniaturized, and lightweight, suitable
      for chronic implantation in small freely behaving animals. The design of this
      system is scalable and its manufacturing is cost effective through batch
      fabrication using microelectromechanical systems (MEMS) technology. It can be
      adopted by other groups and customized for specific needs of individual
      experiments. 

PMID- 25999822
TI  - Modeling human perception of orientation in altered gravity.
AB  - Altered gravity environments, such as those experienced by astronauts, impact
      spatial orientation perception, and can lead to spatial disorientation and
      sensorimotor impairment. To more fully understand and quantify the impact of
      altered gravity on orientation perception, several mathematical models have been
      proposed. The utricular shear, tangent, and the idiotropic vector models aim to
      predict static perception of tilt in hyper-gravity. Predictions from these prior
      models are compared to the available data, but are found to systematically err
      from the perceptions experimentally observed. Alternatively, we propose a
      modified utricular shear model for static tilt perception in hyper-gravity.
      Previous dynamic models of vestibular function and orientation perception are
      limited to 1 G. Specifically, they fail to predict the characteristic
      overestimation of roll tilt observed in hyper-gravity environments. To address
      this, we have proposed a modification to a previous observer-type canal-otolith
      interaction model based upon the hypothesis that the central nervous system (CNS)
      treats otolith stimulation in the utricular plane differently than stimulation
      out of the utricular plane. Here we evaluate our modified utricular shear and
      modified observer models in four altered gravity motion paradigms: (a) static
      roll tilt in hyper-gravity, (b) static pitch tilt in hyper-gravity, (c) static
      roll tilt in hypo-gravity, and (d) static pitch tilt in hypo-gravity. The
      modified models match available data in each of the conditions considered. Our
      static modified utricular shear model and dynamic modified observer model may be
      used to help quantitatively predict astronaut perception of orientation in
      altered gravity environments. 

PMID- 25999824
TI  - The overlooked potential for social factors to improve effectiveness of brain
      computer interfaces.

PMID- 25999825
TI  - Attention to sound improves auditory reliability in audio-tactile spatial optimal
      integration.
AB  - The role of attention on multisensory processing is still poorly understood. In
      particular, it is unclear whether directing attention toward a sensory cue
      dynamically reweights cue reliability during integration of multiple sensory
      signals. In this study, we investigated the impact of attention in combining
      audio-tactile signals in an optimal fashion. We used the Maximum Likelihood
      Estimation (MLE) model to predict audio-tactile spatial localization on the body
      surface. We developed a new audio-tactile device composed by several small units,
      each one consisting of a speaker and a tactile vibrator independently
      controllable by external software. We tested participants in an attentional and a
      non-attentional condition. In the attentional experiment, participants performed
      a dual task paradigm: they were required to evaluate the duration of a sound
      while performing an audio-tactile spatial task. Three unisensory or multisensory
      stimuli, conflictual or not conflictual sounds and vibrations arranged along the
      horizontal axis, were presented sequentially. In the primary task participants
      had to evaluate in a space bisection task the position of the second stimulus
      (the probe) with respect to the others (the standards). In the secondary task
      they had to report occasionally changes in duration of the second auditory
      stimulus. In the non-attentional task participants had only to perform the
      primary task (space bisection). Our results showed an enhanced auditory precision
      (and auditory weights) in the auditory attentional condition with respect to the
      control non-attentional condition. The results of this study support the idea
      that modality-specific attention modulates multisensory integration. 

PMID- 25999826
TI  - Dissociation of agency and body ownership following visuomotor temporal
      recalibration.
AB  - Bodily self-consciousness consists of one's sense of agency (I am causing an
      action) and body ownership (my body belongs to me). Both stem from the temporal
      congruence between different modalities, although some visuomotor temporal
      incongruence is acceptable for agency. To examine the association or dissociation
      between agency and body ownership in the context of different temporal
      sensitivities, we applied a temporal recalibration paradigm, in which subjective
      synchrony between asynchronous hand action and its visual feedback can be
      perceived after exposure to the asynchronous visuomotor stimulation. In the
      experiment, participants continuously clasped and unclasped their hand while
      watching an online video of their hand that was presented with delays of 50, 110,
      170, 230, 290, and 350 ms. Then, they rated a video of their hand with a delay of
      50 ms (test stimulus) with respect to the synchrony between hand action and hand
      video and the perceived agency over the video. Moreover, proprioceptive drift of
      participants' hand location toward the hand video during the exposure was
      measured as an index of illusory body ownership. Results indicated that
      perception of agency emerged over the delayed hand video as subjective visuomotor
      synchrony was recalibrated, but that body ownership did not emerge for the
      delayed video, even after the recalibration. We suggest that there is a
      dissociation between agency and body ownership following visuomotor temporal
      recalibration. 

PMID- 25999827
TI  - Acute intracerebral treatment with amyloid-beta (1-42) alters the profile of
      neuronal oscillations that accompany LTP induction and results in impaired LTP in
      freely behaving rats.
AB  - Accumulation of amyloid plaques comprises one of the major hallmarks of
      Alzheimer's disease (AD). In rodents, acute treatment with amyloid-beta (Abeta; 1
      42) elicits immediate debilitating effects on hippocampal long-term potentiation
      (LTP). Whereas LTP contributes to synaptic information storage, information is
      transferred across neurons by means of neuronal oscillations. Furthermore,
      changes in theta-gamma oscillations, that appear during high-frequency
      stimulation (HFS) to induce LTP, predict whether successful LTP will occur. Here,
      we explored if intra-cerebral treatment with Abeta(1-42), that prevents LTP, also
      results in alterations of hippocampal oscillations that occur during HFS of the
      perforant path-dentate gyrus synapse in 6-month-old behaving rats. HFS resulted
      in LTP that lasted for over 24 h. In Abeta-treated animals, LTP was significantly
      prevented. During HFS, spectral power for oscillations below 100 Hz (delta,
      theta, alpha, beta and gamma) was significantly higher in Abeta-treated animals
      compared to controls. In addition, the trough-to-peak amplitudes of theta and
      gamma cycles were higher during HFS in Abeta-treated animals. We also observed a
      lower amount of envelope-to-signal correlations during HFS in Abeta-treated
      animals. Overall, the characteristic profile of theta-gamma oscillations that
      accompany successful LTP induction was disrupted. These data indicate that
      alterations in network oscillations accompany Abeta-effects on hippocampal LTP.
      This may comprise an underlying mechanism through which disturbances in synaptic
      information storage and hippocampus-dependent memory occurs in AD. 

PMID- 25999828
TI  - Pre-stimulus BOLD-network activation modulates EEG spectral activity during
      working memory retention.
AB  - Working memory (WM) processes depend on our momentary mental state and therefore
      exhibit considerable fluctuations. Here, we investigate the interplay of task
      preparatory and task-related brain activity as represented by pre-stimulus BOLD
      fluctuations and spectral EEG from the retention periods of a visual WM task.
      Visual WM is used to maintain sensory information in the brain enabling the
      performance of cognitive operations and is associated with mental health. We
      tested 22 subjects simultaneously with EEG and fMRI while performing a visuo
      verbal Sternberg task with two different loads, allowing for the temporal
      separation of preparation, encoding, retention and retrieval periods. Four
      temporally coherent networks (TCNs)-the default mode network (DMN), the dorsal
      attention, the right and the left WM network-were extracted from the continuous
      BOLD data by means of a group ICA. Subsequently, the modulatory effect of these
      networks' pre-stimulus activation upon retention-related EEG activity in the
      theta, alpha, and beta frequencies was analyzed. The obtained results are
      informative in the context of state-dependent information processing. We were
      able to replicate two well-known load-dependent effects: the frontal-midline
      theta increase during the task and the decrease of pre-stimulus DMN activity. As
      our main finding, these two measures seem to depend on each other as the
      significant negative correlations at frontal-midline channels suggested. Thus,
      suppressed pre-stimulus DMN levels facilitated later task related frontal midline
      theta increases. In general, based on previous findings that neuronal coupling in
      different frequency bands may underlie distinct functions in WM retention, our
      results suggest that processes reflected by spectral oscillations during
      retention seem not only to be "online" synchronized with activity in different
      attention-related networks but are also modulated by activity in these networks
      during preparation intervals. 

PMID- 25999829
TI  - Cerebellar damage impairs the self-rating of regret feeling in a gambling task.
AB  - Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in
      processing emotions and feelings. Moreover recent studies showed a cerebellar
      involvement in pathologies such as autism, schizophrenia and alexithymia, in
      which emotional processing have been found altered. However, cerebellar function
      in the modulation of emotional responses remains debated. In this study, emotions
      that are involved directly in decision-making were examined in 15 patients (six
      males; age range 17-60 years) affected by cerebellar damage and 15 well matched
      healthy controls. We used a gambling task, in which subjects' choices and
      evaluation of outcomes with regard to their anticipated and actual emotional
      impact were analyzed. Emotions, such as regret and relief, were elicited, based
      on the outcome of the unselected gamble. Interestingly, despite their ability to
      avoid regret in subsequent choices, patients affected by cerebellar lesions were
      significantly impaired in evaluating the feeling of regret subjectively. These
      results demonstrate that the cerebellum is involved in conscious recognizing of
      negative feelings caused by the sense of self-responsibility for an incorrect
      decision. 

PMID- 25999830
TI  - Distinct patterns of outcome valuation and amygdala-prefrontal cortex synaptic
      remodeling in adolescence and adulthood.
AB  - Adolescent behavior is typified by increased risk-taking, reward- and novelty
      seeking, as well as an augmented need for social and environmental stimulation.
      This behavioral phenotype may result from alterations in outcome valuation or
      reward learning. In the present set of experiments, we directly compared adult
      and adolescent animals on tasks measuring both of these processes. Additionally,
      we examined developmental differences in dopamine D1-like receptor (D1R),
      dopamine D2-like receptor (D2R), and polysialylated neural cell adhesion molecule
      (PSA-NCAM) expression in animals that were trained on an effortful reward
      valuation task, given that these proteins play an important role in the
      functional development of the amygdala-prefrontocortical (PFC) circuit and
      mesocorticolimbic dopamine system. We found that adolescent animals were not
      different from adults in appetitive associative learning, but exhibited distinct
      pattern of responses to differences in outcome values, which was paralleled by an
      enhanced motivation to invest effort to obtain larger rewards. There were no
      differences in D2 receptor expression, but D1 receptor expression was
      significantly reduced in the striatum of animals that had experiences with reward
      learning during adolescence compared to animals that went through the same
      experiences in adulthood. We observed increased levels of PSA-NCAM expression in
      both PFC and amygdala of late adolescents compared to adults that were previously
      trained on an effortful reward valuation task. PSA-NCAM levels in PFC were
      strongly and positively associated with high effort/reward (HER) choices in
      adolescents, but not in adult animals. Increased levels of PSA-NCAM expression in
      adolescents may index increased structural plasticity and represent a neural
      correlate of a reward sensitive endophenotype. 

PMID- 25999831
TI  - Audience entrainment during live contemporary dance performance: physiological
      and cognitive measures.
AB  - Perceiving and synchronizing to a piece of dance is a remarkable skill in humans.
      Research in this area is very recent and has been focused mainly on entrainment
      produced by regular rhythms. Here, we investigated entrainment effects on
      spectators perceiving a non-rhythmic and extremely slow performance issued from
      contemporary dance. More specifically, we studied the relationship between
      subjective experience and entrainment produced by perceiving this type of
      performance. We defined two types of entrainment. Physiological entrainment
      corresponded to cardiovascular and respiratory coordinated activities. Cognitive
      entrainment was evaluated through cognitive tasks that quantified time
      distortion. These effects were thought to reflect attunement of a participant'
      internal temporal clock to the particularly slow pace of the danced movement.
      Each participant' subjective experience-in the form of responses to
      questionnaires-were collected and correlated with cognitive and physiological
      entrainment. We observe: (a) a positive relationship between psychological
      entrainment and attention to breathing (their own one or that of dancers); and
      (b) a positive relationship between cognitive entrainment (reflected as an under
      estimation of time following the performance) and attention to their own
      breathing, and attention to the muscles' dancers. Overall, our results suggest a
      close relationship between attention to breathing and entrainment. This proof-of
      concept pilot study was intended to prove the feasibility of a quantitative
      situated paradigm. This research is inscribed in a large-scale interdisciplinary
      project of dance spectating (labodanse.org). 

PMID- 25999832
TI  - Being in the zone: physiological markers of togetherness in joint improvisation.
AB  - Performers improvising together describe special moments of 'being in the zone' -
      periods of high performance, synchrony, and enhanced sense of togetherness.
      Existing evidence suggests a possible route for attaining togetherness -
      interpersonal synchrony, the fine-grained sensory-motor coordination that
      promotes social connectedness. Here, we investigated the physiological
      characteristics of togetherness using a practice from theater and dance, the
      mirror game. Pairs of expert improvisers jointly improvised synchronized linear
      motion, while their motion tracks and cardiovascular activity were continuously
      monitored. Players also provided dynamic ratings of togetherness while watching
      video recordings of their games. We identified periods of togetherness using
      kinematic and subjective markers and assessed their physiological
      characteristics. The kinematic and the subjective measures of togetherness showed
      some agreement, with more extensive game periods being marked by the subjective
      than the kinematic one. Game rounds with high rates of togetherness were
      characterized by increased players' cardiovascular activity, increased
      correlation of players' heart rates (HRs), and increased motion intensity. By
      comparing motion segments with similar motion intensity, we showed that moments
      of togetherness in the mirror game were marked by increased players' HRs,
      regardless of motion intensity. This pattern was robust for the subjectively
      defined periods of togetherness, while showing a marginal effect for the
      kinematically defined togetherness. Building upon similar findings in flow
      research we suggest that the observed increase of players' HRs during
      togetherness periods in the mirror game might indicate the enhanced engagement
      and enjoyment reported by performers going into 'the zone.' The suggested
      approach, combining temporal measurements of kinematic, physiological and
      subjective responses, demonstrates how the dynamics of spontaneously emerging
      dyadic states can be studied empirically. 

PMID- 25999833
TI  - Using a quadratic parameter sinusoid model to characterize the structure of EEG
      sleep spindles.
AB  - Sleep spindles are essentially non-stationary signals that display time and
      frequency-varying characteristics within their envelope, which makes it difficult
      to accurately identify its instantaneous frequency and amplitude. To allow a
      better parameterization of the structure of spindle, we propose modeling spindles
      using a Quadratic Parameter Sinusoid (QPS). The QPS is well suited to model
      spindle activity as it utilizes a quadratic representation to capture the
      inherent duration and frequency variations within spindles. The effectiveness of
      our proposed model and estimation technique was quantitatively evaluated in
      parameter determination experiments using simulated spindle-like signals and real
      spindles in the presence of background EEG. We used the QPS parameters to predict
      the energy and frequency of spindles with a mean accuracy of 92.34 and 97.73%
      respectively. We also show that the QPS parameters provide a quantification of
      the amplitude and frequency variations occurring within sleep spindles that can
      be observed visually and related to their characteristic "waxing and waning"
      shape. We analyze the variations in the parameters values to present how they can
      be used to understand the inter- and intra-participant variations in spindle
      structure. Finally, we present a comparison of the QPS parameters of spindles and
      non-spindles, which shows a substantial difference in parameter values between
      the two classes. 

PMID- 25999834
TI  - Real-time vision, tactile cues, and visual form agnosia: removing haptic feedback
      from a "natural" grasping task induces pantomime-like grasps.
AB  - Investigators study the kinematics of grasping movements (prehension) under a
      variety of conditions to probe visuomotor function in normal and brain-damaged
      individuals. "Natural" prehensile acts are directed at the goal object and are
      executed using real-time vision. Typically, they also entail the use of tactile,
      proprioceptive, and kinesthetic sources of haptic feedback about the object
      ("haptics-based object information") once contact with the object has been made.
      Natural and simulated (pantomimed) forms of prehension are thought to recruit
      different cortical structures: patient DF, who has visual form agnosia following
      bilateral damage to her temporal-occipital cortex, loses her ability to scale her
      grasp aperture to the size of targets ("grip scaling") when her prehensile
      movements are based on a memory of a target previewed 2 s before the cue to
      respond or when her grasps are directed towards a visible virtual target but she
      is denied haptics-based information about the target. In the first of two
      experiments, we show that when DF performs real-time pantomimed grasps towards a
      7.5 cm displaced imagined copy of a visible object such that her fingers make
      contact with the surface of the table, her grip scaling is in fact quite normal.
      This finding suggests that real-time vision and terminal tactile feedback are
      sufficient to preserve DF's grip scaling slopes. In the second experiment, we
      examined an "unnatural" grasping task variant in which a tangible target (along
      with any proxy such as the surface of the table) is denied (i.e., no terminal
      tactile feedback). To do this, we used a mirror-apparatus to present virtual
      targets with and without a spatially coincident copy for the participants to
      grasp. We compared the grasp kinematics from trials with and without terminal
      tactile feedback to a real-time-pantomimed grasping task (one without tactile
      feedback) in which participants visualized a copy of the visible target as
      instructed in our laboratory in the past. Compared to natural grasps, removing
      tactile feedback increased RT, slowed the velocity of the reach, reduced in
      flight grip aperture, increased the slopes relating grip aperture to target
      width, and reduced the final grip aperture (FGA). All of these effects were also
      observed in the real time-pantomime grasping task. These effects seem to be
      independent of those that arise from using the mirror in general as we also
      compared grasps directed towards virtual targets to those directed at real ones
      viewed directly through a pane of glass. These comparisons showed that the grasps
      directed at virtual targets increased grip aperture, slowed the velocity of the
      reach, and reduced the slopes relating grip aperture to the widths of the target.
      Thus, using the mirror has real consequences on grasp kinematics, reflecting the
      importance of task-relevant sources of online visual information for the
      programming and updating of natural prehensile movements. Taken together, these
      results provide compelling support for the view that removing terminal tactile
      feedback, even when the grasps are target-directed, induces a switch from real
      time visual control towards one that depends more on visual perception and
      cognitive supervision. Providing terminal tactile feedback and real-time visual
      information can evidently keep the dorsal visuomotor system operating normally
      for prehensile acts. 

PMID- 25999836
TI  - The embodied brain: towards a radical embodied cognitive neuroscience.
AB  - In this programmatic paper we explain why a radical embodied cognitive
      neuroscience is needed. We argue for such a claim based on problems that have
      arisen in cognitive neuroscience for the project of localizing function to
      specific brain structures. The problems come from research concerned with
      functional and structural connectivity that strongly suggests that the function a
      brain region serves is dynamic, and changes over time. We argue that in order to
      determine the function of a specific brain area, neuroscientists need to zoom out
      and look at the larger organism-environment system. We therefore argue that
      instead of looking to cognitive psychology for an analysis of psychological
      functions, cognitive neuroscience should look to an ecological dynamical
      psychology. A second aim of our paper is to develop an account of embodied
      cognition based on the inseparability of cognitive and emotional processing in
      the brain. We argue that emotions are best understood in terms of action
      readiness (Frijda, 1986, 2007) in the context of the organism's ongoing skillful
      engagement with the environment (Rietveld, 2008; Bruineberg and Rietveld, 2014;
      Kiverstein and Rietveld, 2015, forthcoming). States of action readiness involve
      the whole living body of the organism, and are elicited by possibilities for
      action in the environment that matter to the organism. Since emotion and
      cognition are inseparable processes in the brain it follows that what is true of
      emotion is also true of cognition. Cognitive processes are likewise processes
      taking place in the whole living body of an organism as it engages with relevant
      possibilities for action. 

PMID- 25999835
TI  - Altered resting-state EEG source functional connectivity in schizophrenia: the
      effect of illness duration.
AB  - Despite the increasing body of evidence supporting the hypothesis of
      schizophrenia as a disconnection syndrome, studies of resting-state EEG Source
      Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse.
      The aim of the present study was to investigate resting-state EEG-SFC in 77
      stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy
      volunteers (HV). In order to study the effect of illness duration, SCZ were
      divided in those with a short duration of disease (SDD; n = 25) and those with a
      long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes
      closed condition were analyzed and lagged phase synchronization (LPS) indices
      were calculated for each ROI pair in the source-space EEG data. In delta and
      theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in
      frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ
      showed lower frontal EEG-SFC compared with HV whereas no differences were found
      between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs
      and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC
      compared with HV. In the gamma band, SDD had greater connectivity values compared
      with LDD and HV. This study suggests that resting state brain network
      connectivity is abnormally organized in schizophrenia, with different patterns
      for the different EEG frequency components and that EEG can be a powerful tool to
      further elucidate the complexity of such disordered connectivity. 

PMID- 25999837
TI  - Dissociable contribution of the parietal and frontal cortex to coding movement
      direction and amplitude.
AB  - To reach for an object, we must convert its spatial location into an appropriate
      motor command, merging movement direction and amplitude. In humans, it has been
      suggested that this visuo-motor transformation occurs in a dorsomedial parieto
      frontal pathway, although the causal contribution of the areas constituting the
      "reaching circuit" remains unknown. Here we used transcranial magnetic
      stimulation (TMS) in healthy volunteers to disrupt the function of either the
      medial intraparietal area (mIPS) or dorsal premotor cortex (PMd), in each
      hemisphere. The task consisted in performing step-tracking movements with the
      right wrist towards targets located in different directions and eccentricities;
      targets were either visible for the whole trial (Target-ON) or flashed for 200 ms
      (Target-OFF). Left and right mIPS disruption led to errors in the initial
      direction of movements performed towards contralateral targets. These errors were
      corrected online in the Target-ON condition but when the target was flashed for
      200 ms, mIPS TMS manifested as a larger endpoint spreading. In contrast, left PMd
      virtual lesions led to higher acceleration and velocity peaks-two parameters
      typically used to probe the planned movement amplitude-irrespective of the target
      position, hemifield and presentation condition; in the Target-OFF condition, left
      PMd TMS induced overshooting and increased the endpoint dispersion along the axis
      of the target direction. These results indicate that left PMd intervenes in
      coding amplitude during movement preparation. The critical TMS timings leading to
      errors in direction and amplitude were different, namely 160-100 ms before
      movement onset for mIPS and 100-40 ms for left PMd. TMS applied over right PMd
      had no significant effect. These results demonstrate that, during motor
      preparation, direction and amplitude of goal-directed movements are processed by
      different cortical areas, at distinct timings, and according to a specific
      hemispheric organization. 

PMID- 25999839
TI  - Opportunities for concurrent transcranial magnetic stimulation and
      electroencephalography to characterize cortical activity in stroke.
AB  - Stroke is the leading cause of disability in the United States. Despite the high
      incidence and mortality of stroke, sensitive and specific brain-based biomarkers
      predicting persisting disabilities are lacking. Both neuroimaging techniques like
      electroencephalography (EEG) and non-invasive brain stimulation (NIBS) techniques
      such as transcranial magnetic stimulation (TMS) have proven useful in predicting
      prognosis, recovery trajectories and response to rehabilitation in individuals
      with stroke. We propose, however, that additional synergetic effects can be
      achieved by simultaneously combining both approaches. Combined TMS-EEG is able to
      activate discrete cortical regions and directly assess local cortical reactivity
      and effective connectivity within the network independent of the integrity of
      descending fiber pathways and also outside the motor system. Studying cortical
      reactivity and connectivity in patients with stroke TMS-EEG may identify salient
      neural mechanisms underlying motor disabilities and lead to novel biomarkers of
      stroke pathophysiology which can then be used to assess, monitor, and refine
      rehabilitation approaches for individuals with significant disability to improve
      outcomes and quality of life after stroke. 

PMID- 25999838
TI  - Automaticity of walking: functional significance, mechanisms, measurement and
      rehabilitation strategies.
AB  - Automaticity is a hallmark feature of walking in adults who are healthy and well
      functioning. In the context of walking, "automaticity" refers to the ability of
      the nervous system to successfully control typical steady state walking with
      minimal use of attention-demanding executive control resources. Converging lines
      of evidence indicate that walking deficits and disorders are characterized in
      part by a shift in the locomotor control strategy from healthy automaticity to
      compensatory executive control. This is potentially detrimental to walking
      performance, as an executive control strategy is not optimized for locomotor
      control. Furthermore, it places excessive demands on a limited pool of executive
      reserves. The result is compromised ability to perform basic and complex walking
      tasks and heightened risk for adverse mobility outcomes including falls.
      Strategies for rehabilitation of automaticity are not well defined, which is due
      to both a lack of systematic research into the causes of impaired automaticity
      and to a lack of robust neurophysiological assessments by which to gauge
      automaticity. These gaps in knowledge are concerning given the serious functional
      implications of compromised automaticity. Therefore, the objective of this
      article is to advance the science of automaticity of walking by consolidating
      evidence and identifying gaps in knowledge regarding: (a) functional significance
      of automaticity; (b) neurophysiology of automaticity; 

PMID- 25999840
TI  - The thinker: opposing directionality of lighting bias within sculptural artwork.
AB  - Individuals tend to perceive the direction of light to come from above and
      slightly from the left; it has been speculated that this phenomenon is also
      producing similar lighting preferences within 2-dimensional artworks (e.g.,
      paintings, advertisements). The purpose of the present study was to address if
      lighting bias was present in the 3-dimensional medium of sculpture by
      implementing a virtual art gallery lighting paradigm. Thirty-nine participants
      completed a computer task that consisted of 48 galleries each containing one
      sculpture (24 original sculptures, 24 mirror-reversed) which was surrounded by
      eight lights (above/below, left/right, front/back). Participants would select one
      light source to illuminate the sculpture in a manner they perceived to be the
      most aesthetically pleasing. The results indicated a significant preference for
      lights positioned from above and from the right, a finding that is contradictory
      to previous lighting bias research examining artworks. An interpretation for the
      rightward bias applies the perceptual concept of subjective lighting equality.
      Objects illuminated from the left typically appear brighter in comparison to
      right-side lighting; in sculpture, however, increased luminosity can reduce the
      sculptural detail, and may have been compensated via right-side lighting choices
      within the lighting task. 

PMID- 25999842
TI  - Relationship between structural brainstem and brain plasticity and lower-limb
      training in spinal cord injury: a longitudinal pilot study.
AB  - Rehabilitative training has shown to improve significantly motor outcomes and
      functional walking capacity in patients with incomplete spinal cord injury
      (iSCI). However, whether performance improvements during rehabilitation relate to
      brain plasticity or whether it is based on functional adaptation of movement
      strategies remain uncertain. This study assessed training improvement-induced
      structural brain plasticity in chronic iSCI patients using longitudinal MRI. We
      used tensor-based morphometry (TBM) to analyze longitudinal brain volume changes
      associated with intensive virtual reality (VR)-augmented lower limb training in
      nine traumatic iSCI patients. The MRI data was acquired before and after a 4-week
      training period (16-20 training sessions). Before training, voxel-based
      morphometry (VBM) and voxel-based cortical thickness (VBCT) assessed baseline
      morphometric differences in nine iSCI patients compared to 14 healthy controls.
      The intense VR-augmented training of limb control improved significantly balance,
      walking speed, ambulation, and muscle strength in patients. Retention of clinical
      improvements was confirmed by the 3-4 months follow-up. In patients relative to
      controls, VBM revealed reductions of white matter volume within the brainstem and
      cerebellum and VBCT showed cortical thinning in the primary motor cortex. Over
      time, TBM revealed significant improvement-induced volume increases in the left
      middle temporal and occipital gyrus, left temporal pole and fusiform gyrus, both
      hippocampi, cerebellum, corpus callosum, and brainstem in iSCI patients. This
      study demonstrates structural plasticity at the cortical and brainstem level as a
      consequence of VR-augmented training in iSCI patients. These structural changes
      may serve as neuroimaging biomarkers of VR-augmented lower limb
      neurorehabilitation in addition to performance measures to detect improvements in
      rehabilitative training. 

PMID- 25999841
TI  - Structural and effective connectivity reveals potential network-based influences
      on category-sensitive visual areas.
AB  - Visual category perception is thought to depend on brain areas that respond
      specifically when certain categories are viewed. These category-sensitive areas
      are often assumed to be "modules" (with some degree of processing autonomy) and
      to act predominantly on feedforward visual input. This modular view can be
      complemented by a view that treats brain areas as elements within more complex
      networks and as influenced by network properties. This network-oriented viewpoint
      is emerging from studies using either diffusion tensor imaging to map structural
      connections or effective connectivity analyses to measure how their functional
      responses influence each other. This literature motivates several hypotheses that
      predict category-sensitive activity based on network properties. Large, long
      range fiber bundles such as inferior fronto-occipital, arcuate and inferior
      longitudinal fasciculi are associated with behavioral recognition and could play
      crucial roles in conveying backward influences on visual cortex from anterior
      temporal and frontal areas. Such backward influences could support top-down
      functions such as visual search and emotion-based visual modulation. Within
      visual cortex itself, areas sensitive to different categories appear well
      connected (e.g., face areas connect to object- and motion sensitive areas) and
      their responses can be predicted by backward modulation. Evidence supporting
      these propositions remains incomplete and underscores the need for better
      integration of DTI and functional imaging. 

PMID- 25999843
TI  - Advances in modern mental chronometry.

PMID- 25999844
TI  - Dissociation in decision bias mechanism between probabilistic information and
      previous decision.
AB  - Target detection performance is known to be influenced by events in the previous
      trials. It has not been clear, however, whether this bias effect is due to the
      previous sensory stimulus, motor response, or decision. Also it remains open
      whether or not the previous trial effect emerges via the same mechanism as the
      effect of knowledge about the target probability. In the present study, we asked
      normal human subjects to make a decision about the presence or absence of a
      visual target. We presented a pre-cue indicating the target probability before
      the stimulus, and also a decision-response mapping cue after the stimulus so as
      to tease apart the effect of decision from that of motor response. We found that
      the target detection performance was significantly affected by the probability
      cue in the current trial and also by the decision in the previous trial. While
      the information about the target probability modulated the decision criteria, the
      previous decision modulated the sensitivity to target-relevant sensory signals (d
      prime). Using functional magnetic resonance imaging (fMRI), we also found that
      activation in the left intraparietal sulcus (IPS) was decreased when the
      probability cue indicated a high probability of the target. By contrast,
      activation in the right inferior frontal gyrus (IFG) was increased when the
      subjects made a target-present decision in the previous trial, but this change
      was observed specifically when the target was present in the current trial.
      Activation in these regions was associated with individual-difference in the
      decision computation parameters. We argue that the previous decision biases the
      target detection performance by modulating the processing of target-selective
      information, and this mechanism is distinct from modulation of decision criteria
      due to expectation of a target. 

PMID- 25999846
TI  - Genetic algorithm supported by graphical processing unit improves the exploration
      of effective connectivity in functional brain imaging.
AB  - Brain regions of human subjects exhibit certain levels of associated activation
      upon specific environmental stimuli. Functional Magnetic Resonance Imaging (fMRI)
      detects regional signals, based on which we could infer the direct or indirect
      neuronal connectivity between the regions. Structural Equation Modeling (SEM) is
      an appropriate mathematical approach for analyzing the effective connectivity
      using fMRI data. A maximum likelihood (ML) discrepancy function is minimized
      against some constrained coefficients of a path model. The minimization is an
      iterative process. The computing time is very long as the number of iterations
      increases geometrically with the number of path coefficients. Using regular Quad
      Core Central Processing Unit (CPU) platform, duration up to 3 months is required
      for the iterations from 0 to 30 path coefficients. This study demonstrates the
      application of Graphical Processing Unit (GPU) with the parallel Genetic
      Algorithm (GA) that replaces the Powell minimization in the standard program code
      of the analysis software package. It was found in the same example that GA under
      GPU reduced the duration to 20 h and provided more accurate solution when
      compared with standard program code under CPU. 

PMID- 25999845
TI  - Restoring the encoding properties of a stochastic neuron model by an exogenous
      noise.
AB  - Here we evaluate the possibility of improving the encoding properties of an
      impaired neuronal system by superimposing an exogenous noise to an external
      electric stimulation signal. The approach is based on the use of mathematical
      neuron models consisting of stochastic HH-like circuit, where the impairment of
      the endogenous presynaptic inputs is described as a subthreshold injected current
      and the exogenous stimulation signal is a sinusoidal voltage perturbation across
      the membrane. Our results indicate that a correlated Gaussian noise, added to the
      sinusoidal signal can significantly increase the encoding properties of the
      impaired system, through the Stochastic Resonance (SR) phenomenon. These results
      suggest that an exogenous noise, suitably tailored, could improve the efficacy of
      those stimulation techniques used in neuronal systems, where the presynaptic
      sensory neurons are impaired and have to be artificially bypassed. 

PMID- 25999847
TI  - Analysis of the role of the low threshold currents IT and Ih in intrinsic delta
      oscillations of thalamocortical neurons.
AB  - Thalamocortical neurons are involved in the generation and maintenance of brain
      rhythms associated with global functional states. The repetitive burst firing of
      TC neurons at delta frequencies (1-4 Hz) has been linked to the oscillations
      recorded during deep sleep and during episodes of absence seizures. To get
      insight into the biophysical properties that are the basis for intrinsic delta
      oscillations in these neurons, we performed a bifurcation analysis of a minimal
      conductance-based thalamocortical neuron model including only the IT channel and
      the sodium and potassium leak channels. This analysis unveils the dynamics of
      repetitive burst firing of TC neurons, and describes how the interplay between
      the amplifying variable mT and the recovering variable hT of the calcium channel
      IT is sufficient to generate low threshold oscillations in the delta band. We
      also explored the role of the hyperpolarization activated cationic current Ih in
      this reduced model and determine that, albeit not required, Ih amplifies and
      stabilizes the oscillation. 

PMID- 25999848
TI  - Mental distress in patients with cerebral visual injury assessed with the german
      brief symptom inventory.
AB  - BACKGROUND: While there are reports on vision-related quality of life in patients
      with vision impairment caused by both ophthalmic and brain diseases, little is
      known about mental distress. In fact, mental distress after cerebral visual
      injury has been widely ignored. METHODS: Mental health symptoms were assessed in
      122 participants with visual field defects after brain damage (72 male, mean age
      58.1 +/- 15.6 years), who completed the German Brief Symptom Inventory (BSI) at
      their homes after they had been asked by phone for their participation. RESULTS:
      Clinically relevant mental distress was present in 25.4% of participants with
      cerebral visual injury. In case of multisensory impairment, an increased amount
      and intensity of mental distress symptoms was observed compared to the subsample
      with only visual impairment. CONCLUSION: Assessment of comorbid mental health
      symptoms appears to be clinically meaningful in brain-damaged patients with
      visual sensory impairment. In case of clinically relevant mental distress,
      psychological supportive therapies are advisable especially in subjects with
      cerebral visual injury and comorbidities affecting other sensory modalities as
      well.

PMID- 25999849
TI  - Exceptional longevity and muscle and fitness related genotypes: a functional in
      vitro analysis and case-control association replication study with SNPs THRH
      rs7832552, IL6 rs1800795, and ACSL1 rs6552828.
AB  - There are several gene variants that are candidates to influence functional
      capacity in long-lived individuals. As such, their potential association with
      exceptional longevity (EL, i.e., reaching 100+ years) deserves analysis. Among
      them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR) gene,
      rs1800795 in the interleukin-6 (IL6) gene and rs6552828 in the coenzyme A
      synthetase long-chain 1 (ACSL1) gene. To gain insight into their functionality
      (which is yet unknown), here we determined for the first time luciferase gene
      reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then
      compared allele/genotype frequencies of the 3 abovementioned variants among
      centenarians [n = 138, age range 100-111 years (114 women)] and healthy controls
      [n = 334, 20-50 years (141 women)] of the same ethnic and geographic origin
      (Spain). We also studied healthy centenarians [n = 79, 100-104 years (40 women)]
      and controls [n = 316, 27-81 years (156 women)] from Italy, and centenarians [n =
      742, 100-116 years (623 women)] and healthy controls [n = 499, 23-59 years (356
      women)] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up
      regulated luciferase activity compared to the C and G-allele, respectively (P =
      0.001). Yet we found no significant association of EL with rs7832552, rs1800795
      or rs6552828 in any of the 3 cohorts. Further research is needed with larger
      cohorts of centenarians of different origin as well as with younger old people. 

PMID- 25999851
TI  - Oxidative stress-dependent changes in immune responses and cell death in the
      substantia nigra after ozone exposure in rat.
AB  - Parkinson's disease has been associated with the selective loss of neurons in the
      substantia nigra pars compacta. Increasing evidence suggests that oxidative
      stress plays a major role. The resulting increase in reactive oxygen species
      triggers a sequence of events that leads to cell damage, activation of microglia
      cells and neuroinflammatory responses. Our objective was to study whether chronic
      exposure to low doses of ozone, which produces oxidative stress itself, induces
      progressive cell death in conjunction with glial alterations in the substantia
      nigra. Animals were exposed to an ozone-free air stream (control) or to low doses
      of ozone for 7, 15, 30, 60, or 90 days. Each group underwent (1)
      spectrophotometric analysis for protein oxidation; (2) western blot testing for
      microglia reactivity and nuclear factor kappa B expression levels; and (3)
      immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB, and COX-2. Our results
      indicate that ozone induces an increase in protein oxidation levels, changes in
      activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed
      an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia
      nigra increased from 7 days up to 90 days of repetitive ozone exposure. These
      results suggest that oxidative stress caused by ozone exposure induces changes in
      inflammatory responses and progressive cell death in the substantia nigra in
      rats, which could also be occurring in Parkinson's disease. 

PMID- 25999852
TI  - Catecholamine-Based Treatment in AD Patients: Expectations and Delusions.
AB  - In Alzheimer disease, the gap between excellence of diagnostics and efficacy of
      therapy is wide. Despite sophisticated imaging and biochemical markers, the
      efficacy of available therapeutic options is limited. Here we examine the
      possibility that assessment of endogenous catecholamine levels in cerebrospinal
      fluid (CSF) may fuel new therapeutic strategies. In reviewing the available
      literature, we consider the effects of levodopa, monoamine oxidase inhibitors,
      and noradrenaline (NE) modulators, showing disparate results. We present a
      preliminary assessment of CSF concentrations of dopamine (DA) and NE, determined
      by HPLC, in a small dementia cohort of either Alzheimer's disease (AD) or
      frontotemporal dementia patients, compared to control subjects. Our data reveal
      detectable levels of DA, NE in CSF, though we found no significant alterations in
      the dementia population as a whole. AD patients exhibit a small impairment of the
      DA axis and a larger increase of NE concentration, likely to represent a
      compensatory mechanism. While waiting for preventive strategies, a pragmatic
      approach to AD may re-evaluate catecholamine modulation, possibly stratified to
      dementia subtypes, as part of the therapeutic armamentarium. 

PMID- 25999850
TI  - Interaction between therapeutic interventions for Alzheimer's disease and
      physiological Abeta clearance mechanisms.
AB  - Most therapeutic agents are designed to target a molecule or pathway without
      consideration of the mechanisms involved in the physiological turnover or removal
      of that target. In light of this and in particular for Alzheimer's disease, a
      number of therapeutic interventions are presently being developed/investigated
      which target the amyloid-beta peptide (Abeta). However, the literature has not
      adequately considered which Abeta physiological clearance pathways are necessary
      and sufficient for the effective action of these therapeutics. In this review, we
      evaluate the therapeutic strategies targeting Abeta presently in clinical
      development, discuss the possible interaction of these treatments with pathways
      that under normal physiological conditions are responsible for the turnover of
      Abeta and highlight possible caveats. We consider immunization strategies
      primarily reliant on a peripheral sink mechanism of action, small molecules that
      are reliant on entry into the CNS and thus degradation pathways within the brain,
      as well as lifestyle interventions that affect vascular, parenchymal and
      peripheral degradation pathways. We propose that effective development of
      Alzheimer's disease therapeutic strategies targeting Abeta peptide will require
      consideration of the age- and disease-specific changes to endogenous Abeta
      clearance mechanisms in order to elicit maximal efficacy. 

PMID- 25999853
TI  - Inhibition deficit in the spatial tendency of the response in multiple-domain
      amnestic mild cognitive impairment. An event-related potential study.
AB  - Longitudinal studies have shown that a high percentage of people with amnestic
      mild cognitive impairment (MCI) develop Alzheimer's disease (AD). Prodromal AD is
      known to involve deficits in executive control processes. In the present study,
      we examined such deficits by recording EEG in 13 single-domain amnestic MCI
      (sdaMCI), 12 multiple-domain amnestic MCI (mdaMCI) and 18 healthy elderly
      (control group, CG) participants while they performed a Simon task. The Simon
      task demands deployment of executive processes because participants have to
      respond to non-spatial features of a lateralized stimulus and inhibit the more
      automatic spatial tendency of the response. We specifically focused on the
      negativity central contralateral (N2cc), an event-related potential (ERP)
      component related to brain activity that prevents the cross-talk between
      direction of spatial attention and manual response preparation. The reaction time
      (RT) was not significantly different among the three groups of participants. The
      percentage of errors (PE) was higher in mdaMCI than in CG and sdaMCI
      participants. In addition, N2cc latency was delayed in mdaMCI (i.e., delayed
      implementation of mechanisms for controlling the spatial tendency of the
      response). The N2cc latency clearly distinguished among mdaMCI and CG/sdaMCI
      participants (area under curve: 0.91). Longer N2cc was therefore associated with
      executive control deficits, which suggests that N2cc latency is a correlate of
      mdaMCI. 

PMID- 25999854
TI  - MicroRNAs modulated by local mIGF-1 expression in mdx dystrophic mice.
AB  - Duchenne muscular dystrophy (DMD) is a X-linked genetic disease in which the
      absence of dystrophin leads to progressive lethal skeletal muscle degeneration.
      It has been demonstrated that among genes which are important for proper muscle
      development and function, micro-RNAs (miRNAs) play a crucial role. Moreover,
      altered levels of miRNAs were found in several muscular disorders, including DMD.
      A specific group of miRNAs, whose expression depends on dystrophin levels and
      whose deregulation explains several DMD pathogenetic traits, has been identified.
      Here, we addressed whether the anabolic activity of mIGF-1 on dystrophic muscle
      is associated with modulation of microRNAs expression. We demonstrated that some
      microRNAs are strictly linked to the dystrophin expression and are not modulated
      by mIGF-1 expression. In contrast, local expression of mIGF-1 promotes the
      modulation of other microRNAs, such as miR-206 and miR-24, along with the
      modulation of muscle specific genes, which are associated with maturation of
      regenerating fibers and with the stabilization of the differentiated muscle
      phenotype. These data suggest that mIGF-1, modifying the expression of some of
      the active players of muscle homeostasis, is able, even in absence of dystrophin
      expression, to activate circuitries that confer robustness to dystrophic muscle. 

PMID- 25999855
TI  - Global integration of the hot-state brain network of appetite predicts short term
      weight loss in older adult.
AB  - Obesity is a public health crisis in North America. While lifestyle interventions
      for weight loss (WL) remain popular, the rate of success is highly variable.
      Clearly, self-regulation of eating behavior is a challenge and patterns of
      activity across the brain may be an important determinant of success. The current
      study prospectively examined whether integration across the Hot-State Brain
      Network of Appetite (HBN-A) predicts WL after 6-months of treatment in older
      adults. Our metric for network integration was global efficiency (GE). The
      present work is a sub-study (n = 56) of an ongoing randomized clinical trial
      involving WL. Imaging involved a baseline food-cue visualization functional MRI
      (fMRI) scan following an overnight fast. Using graph theory to build functional
      brain networks, we demonstrated that regions of the HBN-A (insula, anterior
      cingulate cortex (ACC), superior temporal pole (STP), amygdala and the
      parahippocampal gyrus) were highly integrated as evidenced by the results of a
      principal component analysis (PCA). After accounting for known correlates of WL
      (baseline weight, age, sex, and self-regulatory efficacy) and treatment
      condition, which together contributed 36.9% of the variance in WL, greater GE in
      the HBN-A was associated with an additional 19% of the variance. The ACC of the
      HBN-A was the primary driver of this effect, accounting for 14.5% of the variance
      in WL when entered in a stepwise regression following the covariates, p = 0.0001.
      The HBN-A is comprised of limbic regions important in the processing of emotions
      and visceral sensations and the ACC is key for translating such processing into
      behavioral consequences. The improved integration of these regions may enhance
      awareness of body and emotional states leading to more successful self-regulation
      and to greater WL. This is the first study among older adults to prospectively
      demonstrate that, following an overnight fast, GE of the HBN-A during a food
      visualization task is predictive of WL. 

PMID- 25999856
TI  - Intermanual transfer and bilateral cortical plasticity is maintained in older
      adults after skilled motor training with simple and complex tasks.
AB  - Intermanual transfer refers to the phenomenon whereby unilateral motor training
      induces performance gains in both the trained limb and in the opposite, untrained
      limb. Evidence indicates that intermanual transfer is attenuated in older adults
      following training on a simple ballistic movement task, but not after training on
      a complex task. This study investigated whether differences in plasticity in
      bilateral motor cortices underlie these differential intermanual transfer effects
      in older adults. Twenty young (<35 years-old) and older adults (>65 years)
      trained on a simple (repeated ballistic thumb abduction) and complex (sequential
      finger-thumb opposition) task in separate sessions. Behavioral performance was
      used to quantify intermanual transfer between the dominant (trained) and non
      dominant (untrained) hands. The amplitude of motor-evoked potentials induced by
      single pulse transcranial magnetic stimulation was used to investigate
      excitability changes in bilateral motor cortices. Contrary to predictions, both
      age groups exhibited performance improvements in both hands after unilateral
      skilled motor training with simple and complex tasks. These performance gains
      were accompanied by bilateral increases in cortical excitability in both groups
      for the simple but not the complex task. The findings suggest that advancing age
      does not necessarily influence the capacity for intermanual transfer after
      training with the dominant hand. 

PMID- 25999857
TI  - How do antimalarial drugs reach their intracellular targets?
AB  - Drugs represent the primary treatment available for human malaria, as caused by
      Plasmodium spp. Currently approved drugs and antimalarial drug leads generally
      work against parasite enzymes or activities within infected erythrocytes. To
      reach their specific targets, these chemicals must cross at least three membranes
      beginning with the host cell membrane. Uptake at each membrane may involve
      partitioning and diffusion through the lipid bilayer or facilitated transport
      through channels or carriers. Here, we review the features of available
      antimalarials and examine whether transporters may be required for their uptake.
      Our computational analysis suggests that most antimalarials have high intrinsic
      membrane permeability, obviating the need for uptake via transporters; a subset
      of compounds appear to require facilitated uptake. We also review parasite and
      host transporters that may contribute to drug uptake. Broad permeability channels
      at the erythrocyte and parasitophorous vacuolar membranes of infected cells relax
      permeability constraints on antimalarial drug design; however, this uptake
      mechanism is prone to acquired resistance as the parasite may alter channel
      activity to reduce drug uptake. A better understanding of how antimalarial drugs
      reach their intracellular targets is critical to prioritizing drug leads for
      antimalarial development and may reveal new targets for therapeutic intervention.

PMID- 25999858
TI  - In vitro methods for hazard assessment of industrial chemicals - opportunities
      and challenges.
AB  - Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity immune
      reaction mediated by T-lymphocytes as a result of repeated exposure of an
      allergen primarily on skin. ACD accounts for up to 95% of occupational skin
      diseases, with epoxy resins implicated as one of the most common causes of ACD.
      Efficient high-throughput in vitro screening for accurate identification of
      compounds and materials that may pose hazardous risks in the workplace is
      crucial. At present, the murine local lymph node assay is the 'method of choice'
      for predicting the sensitizing potency of contact allergens. As the 3Rs
      principles of reduction, refinement, and replacement in animal testing has gained
      political and economic momentum, several in vitro screening methods have been
      developed for identifying potential contact allergens. To date, these latter
      methods have been utilized primarily to assess the skin sensitizing potential of
      the chemical components of cosmetic products with scant research attention as to
      the applicability of these methods to industrial chemicals, particularly epoxy
      resins. Herein we review the currently utilized in vitro methods and identify the
      knowledge gaps with regard to assessing the generalizability of in vitro
      screening methods for assessing the skin sensitizing potential of industrial
      chemicals. 

PMID- 25999860
TI  - Beluga (Delphinapterus leucas) granulocytes and monocytes display variable
      responses to in vitro pressure exposures.
AB  - While it is widely known that marine mammals possess adaptations which allow them
      to make repetitive and extended dives to great depths without suffering ill
      effects seen in humans, the response of marine mammal immune cells to diving is
      unknown. Renewed interest in marine mammal dive physiology has arisen due to
      reports of decompression sickness-like symptoms and embolic damage in stranded
      and by-caught animals, and there is concern over whether anthropogenic activities
      can impact marine mammal health by disrupting adaptive dive responses and
      behavior. This work addresses the need for information concerning marine mammal
      immune function during diving by evaluating granulocyte and monocyte
      phagocytosis, and granulocyte activation in belugas (n = 4) in comparison with
      humans (n = 4), with and without in vitro pressure exposures. In addition, the
      potential for additional stressors to impact immune function was investigated by
      comparing the response of beluga cells to pressure between baseline and stressor
      conditions. Granulocyte and monocyte phagocytosis, as well as granulocyte
      activation, were compared between pressure exposed and non-exposed cells for each
      condition, between different pressure profiles and between conditions using mixed
      generalized linear models (alpha = 0.05). The effects of pressure varied between
      species as well by depth, compression/decompression rates, and length of
      exposures, and condition for belugas. Pressure induced changes in granulocyte and
      monocyte function in belugas could serve a protective function against dive
      related pathologies and differences in the response between humans and belugas
      could reflect degrees of dive adaptation. The alteration of these responses
      during physiologically challenging conditions may increase the potential for dive
      related in jury and disease in marine mammals. 

PMID- 25999859
TI  - Improving the safety of cell therapy with the TK-suicide gene.
AB  - While opening new frontiers for the cure of malignant and non-malignant diseases,
      the increasing use of cell therapy poses also several new challenges related to
      the safety of a living drug. The most effective and consolidated cell therapy
      approach is allogeneic hematopoietic stem cell transplantation (HSCT), the only
      cure for several patients with high-risk hematological malignancies. The
      potential of allogeneic HSCT is strictly dependent on the donor immune system,
      particularly on alloreactive T lymphocytes, that promote the beneficial graft
      versus-tumor effect (GvT), but may also trigger the detrimental graft-versus-host
      disease (GvHD). Gene transfer technologies allow to manipulate donor T-cells to
      enforce GvT and foster immune reconstitution, while avoiding or controlling GvHD.
      The suicide gene approach is based on the transfer of a suicide gene into donor
      lymphocytes, for a safe infusion of a wide T-cell repertoire, that might be
      selectively controlled in vivo in case of GvHD. The herpes simplex virus
      thymidine kinase (HSV-TK) is the suicide gene most extensively tested in humans.
      Expression of HSV-TK in donor lymphocytes confers lethal sensitivity to the anti
      herpes drug, ganciclovir. Progressive improvements in suicide genes, vector
      technology and transduction protocols have allowed to overcome the toxicity of
      GvHD while preserving the antitumor efficacy of allogeneic HSCT. Several phase I
      II clinical trials in the last 20 years document the safety and the efficacy of
      HSV-TK approach, able to maintain its clear value over the last decades, in the
      rapidly progressing horizon of cancer cellular therapy. 

PMID- 25999861
TI  - In situ single photon confocal imaging of cardiomyocyte T-tubule system from
      Langendorff-perfused hearts.
AB  - Transverse tubules (T-tubules) are orderly invaginations of the sarcolemma in
      mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for
      cardiac excitation-contraction coupling function. T-tubule remodeling is
      recognized as a key player in cardiac dysfunction. Early studies on T-tubule
      structure were based on electron microscopy, which uncovered important
      information about the T-tubule architecture. The advent of fluorescent membrane
      probes allowed the application of confocal microscopy to investigations of T
      tubule structure. Studies have now been extended beyond single cardiomyocytes to
      examine the T-tubule network in intact hearts through in situ confocal imaging of
      Langendorff-perfused hearts. This technique has allowed visualization of T-tubule
      organization in their natural habitat, avoiding the damage induced by isolation
      of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in
      different subepicardial regions in a single intact heart. We review how this
      state-of-the-art imaging technique has provided important mechanistic insights
      into maturation of T-tubules in developing hearts and defined the role of T
      tubule remodeling in development and progression of heart failure. 

PMID- 25999862
TI  - Long-range correlations and patterns of recurrence in children and adults'
      attention to hierarchical displays.
AB  - In order to make sense of a scene, a person must pay attention to several levels
      of nested order, ranging from the most differentiated details of the display to
      the integrated whole. In adults, research shows that the processes of integration
      and differentiation have the signature of self-organization. Does the same hold
      for children? The current study addresses this question with children between 6
      and 9 years of age, using two tasks that require attention to hierarchical
      displays. A group of adults were tested as well, for control purposes. To get at
      the question of self-organization, reaction times were submitted to a detrended
      fluctuation analysis and a recurrence quantification analysis. H exponents show a
      long-range correlations (1/f noise), and recurrence measures (percent
      determinism, maximum line, entropy, and trend), show a deterministic structure of
      variability being characteristic of self-organizing systems. Findings are
      discussed in terms of organism-environment coupling that gives rise to fluid
      attention to hierarchical displays. 

PMID- 25999863
TI  - The hop constituent xanthohumol exhibits hepatoprotective effects and inhibits
      the activation of hepatic stellate cells at different levels.
AB  - Xanthohumol is the principal prenylated flavonoid of the female inflorescences of
      the hop plant. In recent years, various beneficial xanthohumol effects including
      anti-inflammatory, antioxidant, hypoglycemic activities, and anticancer effects
      have been revealed. This review summarizes present studies indicating that
      xanthohumol also inhibits several critical pathophysiological steps during the
      development and course of chronic liver disease, including the activation and pro
      fibrogenic genotype of hepatic stellate cells. Also the various mechanism of
      action and molecular targets of the beneficial xanthohumol effects will be
      described. Furthermore, the potential use of xanthohumol or a xanthohumol
      enriched hop extract as therapeutic agent to combat the progression of chronic
      liver disease will be discussed. It is notable that in addition to its
      hepatoprotective effects, xanthohumol also holds promise as a therapeutic agent
      for treating obesity, dysregulation of glucose metabolism and other components of
      the metabolic syndrome including hepatic steatosis. Thus, therapeutic xanthohumol
      application appears as a promising strategy, particularly in obese patients, to
      inhibit the development as well as the progression of non-alcoholic fatty liver
      disease. 

PMID- 25999864
TI  - Serum testosterone levels and symptom-based depression subtypes in men.
AB  - The main objective of this preliminary study was to further clarify the
      association between testosterone (T) levels and depression by investigating
      symptom-based depression subtypes in a sample of 64 men. The data were taken from
      the ZInEP epidemiology survey. Gonadal hormones of a melancholic (n  = 25) and an
      atypical (n = 14) depression subtype, derived from latent class analysis, were
      compared with those of healthy controls (n  = 18). Serum T was assayed using an
      enzyme-linked immunosorbent assay procedure. Analysis of variance, analysis of
      covariance, non-parametrical tests, and generalized linear regression models were
      performed to examine group differences. The atypical depressive subtype showed
      significantly lower T levels compared with the melancholic depressives. While
      accumulative evidence indicates that, beyond psychosocial characteristics, the
      melancholic and atypical depressive subtypes are also distinguishable by
      biological correlates, the current study expanded this knowledge to include
      gonadal hormones. Further longitudinal research is warranted to disclose
      causality by linking the multiple processes in pathogenesis of depression. 

PMID- 25999866
TI  - Collaborative care models to address late-life depression: lessons for low-and
      middle-income countries.

PMID- 25999867
TI  - Drug abuse, relapse, and prevention education in malaysia: perspective of
      university students through a mixed methods approach.
AB  - In recent years, there have been increasing accounts of illegal substance abuse
      among university students and professional groups in Malaysia. This study looks
      at university students' perceptions about this phenomenon. Students from
      Malaysian universities were asked for their impressions about drug availability
      and abuse, as well as factors contributing to drug abuse and relapse. The
      questionnaire also inquired into their knowledge and views regarding government
      versus private rehabilitation centers, as well as their exposure to, and views
      about, school-based drug-prevention education. Participants were 460 university
      students from five Malaysian states: Penang, Selangor, Kuala Lumpur, Sabah, and
      Sarawak. Results showed gender differences in perceptions of relapse prevention
      strategies, as well as factors leading to drug abuse and relapse. Students also
      believed that drug education would be more effective if initiated between the
      ages of 11 and 12 years, which is slightly older than the common age of first
      exposure, and provided suggestions for improving existing programs. Implications
      of student perceptions for the improvement of current interventions and
      educational programs are discussed. 

PMID- 25999865
TI  - A parietal biomarker for ADHD liability: as predicted by the distributed effects
      perspective model of ADHD.
AB  - BACKGROUND: We previously hypothesized that poor task-directed sensory
      information processing should be indexed by increased weighting of right
      hemisphere (RH) biased attention and visuo-perceptual brain functions during task
      operations and have demonstrated this phenotype in ADHD across multiple studies,
      using multiple methodologies. However, in our recent distributed effects model of
      ADHD, we surmised that this phenotype is not ADHD specific, but rather more
      broadly reflective of any circumstance that disrupts the induction and
      maintenance of an emergent task-directed neural architecture. Under this view,
      increased weighting of RH-biased attention and visuo-perceptual brain functions
      is expected to generally index neurocognitive sets that are not optimized for
      task-directed thought and action, and when durable expressed, liability for ADHD.
      METHOD: The current study tested this view by examining whether previously
      identified rightward parietal EEG asymmetry in ADHD was associated with common
      ADHD characteristics and comorbidities [i.e., ADHD risk factors (RFs)]. RESULTS:
      Barring one exception (non-right handedness), we found that it was. Rightward
      parietal asymmetry (RPA) was associated with carrying the DRD4-7R risk allele,
      being male, having mood disorder, and having anxiety disorder. However,
      differences in the specific expression of RPA were observed, which are discussed
      in relation to possible unique mechanisms underlying ADHD liability in different
      ADHD RFs. CONCLUSION: Rightward parietal asymmetry appears to be a durable
      feature of ADHD liability, as predicted by the Distributed Effects Perspective
      Model of ADHD. Moreover, variability in the expression of this phenotype may shed
      light on different sources of ADHD liability.

PMID- 25999868
TI  - Children can discriminate the authenticity of happy but not sad or fearful facial
      expressions, and use an immature intensity-only strategy.
AB  - Much is known about development of the ability to label facial expressions of
      emotion (e.g., as happy or sad), but rather less is known about the emergence of
      more complex emotional face processing skills. The present study investigates one
      such advanced skill: the ability to tell if someone is genuinely feeling an
      emotion or just pretending (i.e., authenticity discrimination). Previous studies
      have shown that children can discriminate authenticity of happy faces, using
      expression intensity as an important cue, but have not tested the negative
      emotions of sadness or fear. Here, children aged 8-12 years (n = 85) and adults
      (n = 57) viewed pairs of faces in which one face showed a genuinely-felt
      emotional expression (happy, sad, or scared) and the other face showed a pretend
      version. For happy faces, children discriminated authenticity above chance,
      although they performed more poorly than adults. For sad faces, for which our
      pretend and genuine images were equal in intensity, adults could discriminate
      authenticity, but children could not. Neither age group could discriminate
      authenticity of the fear faces. Results also showed that children judged
      authenticity based on intensity information alone for all three expressions
      tested, while adults used a combination of intensity and other factor/s. In
      addition, novel results show that individual differences in empathy (both
      cognitive and affective) correlated with authenticity discrimination for happy
      faces in adults, but not children. Overall, our results indicate late maturity of
      skills needed to accurately determine the authenticity of emotions from facial
      information alone, and raise questions about how this might affect social
      interactions in late childhood and the teenage years. 

PMID- 25999870
TI  - What are the criteria for a good intervention study? Response: "Unrecognized
      ambiguities in validity of intervention research: an example on explicit phonics
      and text-centered teaching".

PMID- 25999871
TI  - First time description of dismantling phenomenon.
AB  - Dismantling is a complex psychic phenomenon, which is not easy to define, and
      little interest has been shown in the subject. The authors of this paper want to
      demonstrate that dismantling is the main defense mechanism in autism, bringing
      about de-consensus of senses. The effects perceived in a child with autistic
      disorder are passivity and lack of thought. The authors' purpose here is to
      define the dismantled state and reveal its underlying process. This paper will
      therefore describe for the first time in literature, the dismantling phenomenon
      and will submit a metapsychological approach of this defense mechanism. 

PMID- 25999872
TI  - Impulsive people have a compulsion for immediate gratification-certain or
      uncertain.
AB  - Impulsivity has been defined as choosing the smaller more immediate reward over a
      larger more delayed reward. The purpose of this research was to gain a deeper
      understanding of the mental processes involved in the decision making. We
      examined participants' rates of delay discounting and probability discounting to
      determine their correlation with time-probability trade-offs. To establish the
      time-probability trade-off rate, participants adjusted a risky, immediate payoff
      to a delayed, certain payoff. In effect, this yielded a probability equivalent of
      waiting time. We found a strong, positive correlation between delay discount
      rates and the time-probability trade-offs. This means that impulsive people have
      a compulsion for immediate gratification, independent of whether the immediate
      reward is certain or uncertain. Thus, they seem not to be concerned with risk but
      rather with time. 

PMID- 25999873
TI  - Transactive memory systems scale for couples: development and validation.
AB  - People in romantic relationships can develop shared memory systems by pooling
      their cognitive resources, allowing each person access to more information but
      with less cognitive effort. Research examining such memory systems in romantic
      couples largely focuses on remembering word lists or performing lab-based tasks,
      but these types of activities do not capture the processes underlying couples'
      transactive memory systems, and may not be representative of the ways in which
      romantic couples use their shared memory systems in everyday life. We adapted an
      existing measure of transactive memory systems for use with romantic couples
      (TMSS-C), and conducted an initial validation study. In total, 397 participants
      who each identified as being a member of a romantic relationship of at least 3
      months duration completed the study. The data provided a good fit to the
      anticipated three-factor structure of the components of couples' transactive
      memory systems (specialization, credibility and coordination), and there was
      reasonable evidence of both convergent and divergent validity, as well as strong
      evidence of test-retest reliability across a 2-week period. The TMSS-C provides a
      valuable tool that can quickly and easily capture the underlying components of
      romantic couples' transactive memory systems. It has potential to help us better
      understand this intriguing feature of romantic relationships, and how shared
      memory systems might be associated with other important features of romantic
      relationships. 

PMID- 25999783
TI  - Precise determination of the mass of the Higgs boson and tests of compatibility
      of its couplings with the standard model predictions using proton collisions at 7
      and 8[Formula: see text].
AB  - Properties of the Higgs boson with mass near 125[Formula: see text] are measured
      in proton-proton collisions with the CMS experiment at the LHC. Comprehensive
      sets of production and decay measurements are combined. The decay channels
      include [Formula: see text], [Formula: see text], [Formula: see text], [Formula:
      see text], [Formula: see text], and [Formula: see text] pairs. The data samples
      were collected in 2011 and 2012 and correspond to integrated luminosities of up
      to 5.1[Formula: see text] at 7[Formula: see text] and up to 19.7[Formula: see
      text] at 8[Formula: see text]. From the high-resolution [Formula: see text] and
      [Formula: see text] channels, the mass of the Higgs boson is determined to be
      [Formula: see text]. For this mass value, the event yields obtained in the
      different analyses tagging specific decay channels and production mechanisms are
      consistent with those expected for the standard model Higgs boson. The combined
      best-fit signal relative to the standard model expectation is [Formula: see text]
      at the measured mass. The couplings of the Higgs boson are probed for deviations
      in magnitude from the standard model predictions in multiple ways, including
      searches for invisible and undetected decays. No significant deviations are
      found.

PMID- 25999869
TI  - Virtues, ecological momentary assessment/intervention and smartphone technology.
AB  - Virtues, broadly understood as stable and robust dispositions for certain
      responses across morally relevant situations, have been a growing topic of
      interest in psychology. A central topic of discussion has been whether studies
      showing that situations can strongly influence our responses provide evidence
      against the existence of virtues (as a kind of stable and robust disposition). In
      this review, we examine reasons for thinking that the prevailing methods for
      examining situational influences are limited in their ability to test
      dispositional stability and robustness; or, then, whether virtues exist. We make
      the case that these limitations can be addressed by aggregating repeated, cross
      situational assessments of environmental, psychological and physiological
      variables within everyday life-a form of assessment often called ecological
      momentary assessment (EMA, or experience sampling). We, then, examine how
      advances in smartphone application (app) technology, and their mass adoption,
      make these mobile devices an unprecedented vehicle for EMA and, thus, the
      psychological study of virtue. We, additionally, examine how smartphones might be
      used for virtue development by promoting changes in thought and behavior within
      daily life; a technique often called ecological momentary intervention (EMI).
      While EMA/I have become widely employed since the 1980s for the purposes of
      understanding and promoting change amongst clinical populations, few EMA/I
      studies have been devoted to understanding or promoting virtues within non
      clinical populations. Further, most EMA/I studies have relied on journaling,
      PDAs, phone calls and/or text messaging systems. We explore how smartphone app
      technology provides a means of making EMA a more robust psychological method, EMI
      a more robust way of promoting positive change, and, as a result, opens up new
      possibilities for studying and promoting virtues. 

PMID- 25999874
TI  - Working memory and intelligibility of hearing-aid processed speech.
AB  - Previous work suggested that individuals with low working memory capacity may be
      at a disadvantage in adverse listening environments, including situations with
      background noise or substantial modification of the acoustic signal. This study
      explored the relationship between patient factors (including working memory
      capacity) and intelligibility and quality of modified speech for older
      individuals with sensorineural hearing loss. The modification was created using a
      combination of hearing aid processing [wide-dynamic range compression (WDRC) and
      frequency compression (FC)] applied to sentences in multitalker babble. The
      extent of signal modification was quantified via an envelope fidelity index. We
      also explored the contribution of components of working memory by including
      measures of processing speed and executive function. We hypothesized that
      listeners with low working memory capacity would perform more poorly than those
      with high working memory capacity across all situations, and would also be
      differentially affected by high amounts of signal modification. Results showed a
      significant effect of working memory capacity for speech intelligibility, and an
      interaction between working memory, amount of hearing loss and signal
      modification. Signal modification was the major predictor of quality ratings.
      These data add to the literature on hearing-aid processing and working memory by
      suggesting that the working memory-intelligibility effects may be related to
      aggregate signal fidelity, rather than to the specific signal manipulation. They
      also suggest that for individuals with low working memory capacity, sensorineural
      loss may be most appropriately addressed with WDRC and/or FC parameters that
      maintain the fidelity of the signal envelope. 

PMID- 25999876
TI  - Inner speech deficits in people with aphasia.
AB  - Despite the ubiquity of inner speech in our mental lives, methods for objectively
      assessing inner speech capacities remain underdeveloped. The most common means of
      assessing inner speech is to present participants with tasks requiring them to
      silently judge whether two words rhyme. We developed a version of this task to
      assess the inner speech of a population of patients with aphasia and
      corresponding language production deficits. Patients' performance on the silent
      rhyming task was severely impaired relative to controls. Patients' performance on
      this task did not, however, correlate with their performance on a variety of
      other standard tests of overt language and rhyming abilities. In particular,
      patients who were generally unimpaired in their abilities to overtly name objects
      during confrontation naming tasks, and who could reliably judge when two words
      spoken to them rhymed, were still severely impaired (relative to controls) at
      completing the silent rhyme task. A variety of explanations for these results are
      considered, as a means to critically reflecting on the relations among inner
      speech, outer speech, and silent rhyme judgments more generally. 

PMID- 25999882
TI  - Commentary: Continuously cumulating meta-analysis and replicability.

PMID- 25999881
TI  - Addressing the gap: a blueprint for studying bimanual hand preference in infants.

PMID- 25999875
TI  - Deaf children's non-verbal working memory is impacted by their language
      experience.
AB  - Several recent studies have suggested that deaf children perform more poorly on
      working memory tasks compared to hearing children, but these studies have not
      been able to determine whether this poorer performance arises directly from
      deafness itself or from deaf children's reduced language exposure. The issue
      remains unresolved because findings come mostly from (1) tasks that are verbal as
      opposed to non-verbal, and (2) involve deaf children who use spoken communication
      and therefore may have experienced impoverished input and delayed language
      acquisition. This is in contrast to deaf children who have been exposed to a sign
      language since birth from Deaf parents (and who therefore have native language
      learning opportunities within a normal developmental timeframe for language
      acquisition). A more direct, and therefore stronger, test of the hypothesis that
      the type and quality of language exposure impact working memory is to use
      measures of non-verbal working memory (NVWM) and to compare hearing children with
      two groups of deaf signing children: those who have had native exposure to a sign
      language, and those who have experienced delayed acquisition and reduced quality
      of language input compared to their native-signing peers. In this study we
      investigated the relationship between NVWM and language in three groups aged 6-11
      years: hearing children (n = 28), deaf children who were native users of British
      Sign Language (BSL; n = 8), and deaf children who used BSL but who were not
      native signers (n = 19). We administered a battery of non-verbal reasoning, NVWM,
      and language tasks. We examined whether the groups differed on NVWM scores, and
      whether scores on language tasks predicted scores on NVWM tasks. For the two
      executive-loaded NVWM tasks included in our battery, the non-native signers
      performed less accurately than the native signer and hearing groups (who did not
      differ from one another). Multiple regression analysis revealed that scores on
      the vocabulary measure predicted scores on those two executive-loaded NVWM tasks
      (with age and non-verbal reasoning partialled out). Our results suggest that
      whatever the language modality-spoken or signed-rich language experience from
      birth, and the good language skills that result from this early age of
      acquisition, play a critical role in the development of NVWM and in performance
      on NVWM tasks. 

PMID- 25999880
TI  - Why be moral? Children's explicit motives for prosocial-moral action.
AB  - Recent research on young children's morality has stressed the autonomous and
      internal nature of children's moral motivation. However, this research has mostly
      focused on implicit moral motives, whereas children's explicit motives have not
      been investigated directly. This study examined children's explicit motives for
      why they want to engage in prosocial actions and avoid antisocial behavior. A
      total of 195 children aged 4-12 years were interviewed about their motives for
      everyday prosocial-moral actions, as well as reported on their relationship with
      their parents. Children's explicit motives to abstain from antisocial behavior
      were found to be more external and less other-oriented than their motives for
      prosocial action. Motives that reflected higher levels of internal motivation
      became more frequent with age. Moreover, positive parent-child relationships
      predicted more other-oriented motives and greater explication of moral motives.
      Overall, the study provides evidence that children's explicit moral motivation is
      far more heterogeneous than prominent theories of moral development (past and
      present) suggest. 

PMID- 25999879
TI  - Domain general learning: Infants use social and non-social cues when learning
      object statistics.
AB  - Previous research has shown that infants can learn from social cues. But is a
      social cue more effective at directing learning than a non-social cue? This study
      investigated whether 9-month-old infants (N = 55) could learn a visual
      statistical regularity in the presence of a distracting visual sequence when
      attention was directed by either a social cue (a person) or a non-social cue (a
      rectangle). The results show that both social and non-social cues can guide
      infants' attention to a visual shape sequence (and away from a distracting
      sequence). The social cue more effectively directed attention than the non-social
      cue during the familiarization phase, but the social cue did not result in
      significantly stronger learning than the non-social cue. The findings suggest
      that domain general attention mechanisms allow for the comparable learning seen
      in both conditions. 

PMID- 25999877
TI  - Cognitive reflection vs. calculation in decision making.
AB  - Scores on the three-item Cognitive Reflection Test (CRT) have been linked with
      dual-system theory and normative decision making (Frederick, 2005). In
      particular, the CRT is thought to measure monitoring of System 1 intuitions such
      that, if cognitive reflection is high enough, intuitive errors will be detected
      and the problem will be solved. However, CRT items also require numeric ability
      to be answered correctly and it is unclear how much numeric ability vs. cognitive
      reflection contributes to better decision making. In two studies, CRT responses
      were used to calculate Cognitive Reflection and numeric ability; a numeracy scale
      was also administered. Numeric ability, measured on the CRT or the numeracy
      scale, accounted for the CRT's ability to predict more normative decisions (a
      subscale of decision-making competence, incentivized measures of impatient and
      risk-averse choice, and self-reported financial outcomes); Cognitive Reflection
      contributed no independent predictive power. Results were similar whether the two
      abilities were modeled (Study 1) or calculated using proportions (Studies 1 and
      2). These findings demonstrate numeric ability as a robust predictor of superior
      decision making across multiple tasks and outcomes. They also indicate that
      correlations of decision performance with the CRT are insufficient evidence to
      implicate overriding intuitions in the decision-making biases and outcomes we
      examined. Numeric ability appears to be the key mechanism instead. 

PMID- 25999883
TI  - Beauty and cuteness in peripheral vision.
AB  - Guo et al. (2011) showed that attractiveness was detectable in peripheral vision.
      Since there are different types of attractiveness (Rhodes, 2006), we investigated
      how beauty and cuteness are detected in peripheral vision with a brief
      presentation. Participants (n = 45) observed two Japanese female faces for 100
      ms, then were asked to respond which face was more beautiful (or cuter). The
      results indicated that both beauty and cuteness were detectable in peripheral
      vision, but not in the same manner. Discrimination rates for judging beauty were
      invariant in peripheral and central vision, while discrimination rates for
      judging cuteness declined in peripheral vision as compared with central vision.
      This was not explained by lower resolution in peripheral vision. In addition, for
      male participants, it was more difficult to judge cuteness than beauty in
      peripheral vision, thus suggesting that gender differences can have a certain
      effect when judging cuteness. Therefore, central vision might be suitable for
      judging cuteness while judging beauty might not be affected by either central or
      peripheral vision. This might be related with the functional difference between
      beauty and cuteness. 

PMID- 25999878
TI  - Integrating basic research with prevention/intervention to reduce risky substance
      use among college students.
AB  - Too often basic research on etiological processes that contribute to substance
      use outcomes is disconnected from efforts to develop prevention and intervention
      programming. Substance use on college campuses is an area of concern where
      translational efforts that bring together basic scientists and
      prevention/intervention practitioners have potential for high impact. We describe
      an effort at a large, public, urban university in the United States to bring
      together researchers across the campus with expertise in college behavioral
      health with university administration and health/wellness practitioners to
      address college student substance use and mental health. The project "Spit for
      Science" examines how genetic and environmental influences contribute to
      behavioral health outcomes across the college years. We argue that findings
      coming out of basic research can be used to develop more tailored prevention and
      intervention programming that incorporates both biologically and psychosocially
      influenced risk factors. Examples of personalized programming suggest this may be
      a fruitful way to advance the field and reduce risky substance use. 

PMID- 25999884
TI  - Social media and mobile applications in chronic disease prevention and
      management.

PMID- 25999885
TI  - Methodological considerations for documenting the energy demand of dance
      activity: a review.
AB  - Previous research has explored the intensity of dance class, rehearsal, and
      performance and attempted to document the body's physiological adaptation to
      these activities. Dance activity is frequently described as: complex, diverse,
      non-steady state, intermittent, of moderate to high intensity, and with notable
      differences between training and performance intensities and durations. Many
      limitations are noted in the methodologies of previous studies creating barriers
      to consensual conclusion. The present study therefore aims to examine the
      previous body of literature and in doing so, seeks to highlight important
      methodological considerations for future research in this area to strengthen our
      knowledge base. Four recommendations are made for future research. Firstly,
      research should continue to be dance genre specific, with detailed accounts of
      technical and stylistic elements of the movement vocabulary examined given
      wherever possible. Secondly, a greater breadth of performance repertoire, within
      and between genres, needs to be closely examined. Thirdly, a greater focus on
      threshold measurements is recommended due to the documented complex interplay
      between aerobic and anaerobic energy systems. Lastly, it is important for
      research to begin to combine temporal data relating to work and rest periods with
      real-time measurement of metabolic data in work and rest, in order to be able to
      quantify demand more accurately. 

PMID- 25999886
TI  - Different but complementary roles of action and gaze in action observation
      priming: Insights from eye- and motion-tracking measures.
AB  - Action priming following action observation is thought to be caused by the
      observed action kinematics being represented in the same brain areas as those
      used for action execution. But, action priming can also be explained by shared
      goal representations, with compatibility between observation of the agent's gaze
      and the intended action of the observer. To assess the contribution of action
      kinematics and eye-gaze cues in the prediction of an agent's action goal and
      action priming, participants observed actions where the availability of both cues
      was manipulated. Action observation was followed by action execution, and the
      congruency between the target of the agent's and observer's actions, and the
      congruency between the observed and executed action spatial location were
      manipulated. Eye movements were recorded during the observation phase, and the
      action priming was assessed using motion analysis. The results showed that the
      observation of gaze information influenced the observer's prediction speed to
      attend to the target, and that observation of action kinematic information
      influenced the accuracy of these predictions. Motion analysis results showed that
      observed action cues alone primed both spatial incongruent and object congruent
      actions, consistent with the idea that the prime effect was driven by similarity
      between goals and kinematics. The observation of action and eye-gaze cues
      together induced a prime effect complementarily sensitive to object and spatial
      congruency. While observation of the agent's action kinematics triggered an
      object-centered and kinematic-centered action representation, independently, the
      complementary observation of eye-gaze triggered a more fine-grained
      representation illustrating a specification of action kinematics toward the
      selected goal. Even though both cues differentially contributed to action
      priming, their complementary integration led to a more refined pattern of action
      priming. 

PMID- 25999887
TI  - Assessing the accuracy of self-reported self-talk.
AB  - As with most kinds of inner experience, it is difficult to assess actual self
      talk frequency beyond self-reports, given the often hidden and subjective nature
      of the phenomenon. The Self-Talk Scale (STS; Brinthaupt et al., 2009) is a self
      report measure of self-talk frequency that has been shown to possess acceptable
      reliability and validity. However, no research using the STS has examined the
      accuracy of respondents' self-reports. In the present paper, we report a series
      of studies directly examining the measurement of self-talk frequency and
      functions using the STS. The studies examine ways to validate self-reported self
      talk by (1) comparing STS responses from 6 weeks earlier to recent experiences
      that might precipitate self-talk, (2) using experience sampling methods to
      determine whether STS scores are related to recent reports of self-talk over a
      period of a week, and (3) comparing self-reported STS scores to those provided by
      a significant other who rated the target on the STS. Results showed that (1)
      overall self-talk scores, particularly self-critical and self-reinforcing self
      talk, were significantly related to reports of context-specific self-talk; (2)
      high STS scorers reported talking to themselves significantly more often during
      recent events compared to low STS scorers, and, contrary to expectations, (3)
      friends reported less agreement than strangers in their self-other self-talk
      ratings. Implications of the results for the validity of the STS and for
      measuring self-talk are presented. 

PMID- 25999888
TI  - In intergroup conflict, self-sacrifice is stronger among pro-social individuals,
      and parochial altruism emerges especially among cognitively taxed individuals.
AB  - Parochial altruism is decomposed in a tendency to benefit the in-group along with
      a tendency to ignore, derogate, and harm rivaling out-groups. Building off recent
      work suggesting that decisions to cooperate can be relatively fast and intuitive,
      we examine parochial altruism in intergroup conflict when cognitive deliberation
      is rendered difficult or not. Predictions were tested in an experiment using an
      incentivized Intergroup Prisoner's Dilemma-Maximizing Differences Game with 95
      subjects classified as either pro-social or pro-self being randomly allocated to
      high vs. low impulse-control conditions. Results showed, first of all, that self
      sacrificial decisions to contribute were made faster than decisions not to
      contribute, and that faster decision time associated with more positive
      expectations of in-group members. Second, we observed that lowering impulse
      control with a difficult rather than easy Stroop Task increased the amount
      contributed to a pool that benefited in-group members while harming out-group
      members; thus reducing deliberation increased parochial altruism. Finally,
      results replicated earlier work showing that especially pro-social (vs. pro-self)
      individuals contributed more to the in-group and did not lower their
      contributions to the between-group pool that benefitted their in-group and,
      simultaneously, hurt the out-group. This pattern emerged independent of their
      impulse control. Thus, (in-group bounded) cooperation is more prominent among
      individuals with strong rather than weak other-regarding preferences. Moreover,
      the intuitive tendency to cooperate may have evolved in the context of intergroup
      conflict and therefore is sharp-edged-in-group bounded and including willingness
      to aggress out-groups. 

PMID- 25999890
TI  - Corrigendum: Comprehending non-native speakers: theory and evidence for
      adjustment in manner of processing.
AB  - [This corrects the article on p. 1546 in vol. 5, PMID: 25653627.]. 

PMID- 25999891
TI  - Interpersonal value profiles and analysis of adolescent academic performance and
      social thinking.
AB  - The purposes of this study were to identify interpersonal value profiles and find
      out whether there were any differences in academic performance and social
      thinking. The study sample was 885 high school students of whom 49.8% (N = 441)
      were boys and 50.2% (N = 444) were girls. The results show that students with low
      Benevolence and Conformity levels showed higher prevalence of failures and
      repeated the year more often. Furthermore, students with a high level of
      Recognition and Leadership and low Conformity and Benevolence are socially
      incompetent students. Intervention programs should to achieve high levels of
      kindness and consideration, respect for rules and generosity, and diminish the
      perception of recognition by others and exertion of authority. Thus, this study
      shows the values that must be worked on to improve students' Academic Performance
      and social competence. 

PMID- 25999889
TI  - Follow the heart or the head? The interactive influence model of emotion and
      cognition.
AB  - The experience of emotion has a powerful influence on daily-life decision making.
      Following Plato's description of emotion and reason as two horses pulling us in
      opposite directions, modern dual-system models of decision making endorse the
      antagonism between reason and emotion. Decision making is perceived as the
      competition between an emotion system that is automatic but prone to error and a
      reason system that is slow but rational. The reason system (in "the head") reins
      in our impulses (from "the heart") and overrides our snap judgments. However,
      from Darwin's evolutionary perspective, emotion is adaptive, guiding us to make
      sound decisions in uncertainty. Here, drawing findings from behavioral economics
      and neuroeconomics, we provide a new model, labeled "The interactive influence
      model of emotion and cognition," to elaborate the relationship of emotion and
      reason in decision making. Specifically, in our model, we identify factors that
      determine when emotions override reason and delineate the type of contexts in
      which emotions help or hurt decision making. We then illustrate how cognition
      modulates emotion and how they cooperate to affect decision making. 

PMID- 25999892
TI  - Long-lasting semantic interference effects in object naming are not necessarily
      conceptually mediated.
AB  - Long-lasting interference effects in picture naming are induced when objects are
      presented in categorically related contexts in both continuous and blocked cyclic
      paradigms. Less consistent context effects have been reported when the task is
      changed to semantic classification. Experiment 1 confirmed the recent finding of
      cumulative facilitation in the continuous paradigm with living/non-living
      superordinate categorization. To avoid a potential confound involving
      participants responding with the identical superordinate category in related
      contexts in the blocked cyclic paradigm, we devised a novel set of categorically
      related objects that also varied in terms of relative age - a core semantic type
      associated with the adjective word class across languages. Experiment 2
      demonstrated the typical interference effect with these stimuli in basic level
      naming. In Experiment 3, using the identical blocked cyclic paradigm, we failed
      to observe semantic context effects when the same pictures were classified as
      younger-older. Overall, the results indicate the semantic context effects in the
      two paradigms do not share a common origin, with the effect in the continuous
      paradigm arising at the level of conceptual representations or in conceptual-to
      lexical connections while the effect in the blocked cyclic paradigm most likely
      originates at a lexical level of representation. The implications of these
      findings for current accounts of long-lasting interference effects in spoken word
      production are discussed. 

PMID- 25999893
TI  - The role of general dynamic coordination in the handwriting skills of children.
AB  - Difficulties in handwriting are often reported in children with developmental
      coordination disorder, and they represent an important element in the diagnosis.
      The present study was aimed at investigating the relation between motor
      coordination and handwriting skills, and to identify differences in handwriting
      between children without and with coordination difficulties. In particular, we
      asked whether visual-spatial skills have a role as mediating variables between
      motor coordination and handwriting. We assessed motor coordination as well as
      graphic abilities in children aged 7-10 years. Moreover, we evaluated their
      visual-motor integration, visual-spatial skills, and other cognitive abilities
      (memory and planning). We found no relation between motor coordination and
      handwriting skills, while visual-spatial skills (measured by a visual
      constructive task) were related with both. Our conclusion is that visual-spatial
      skills are involved both in general motor coordination and in handwriting, but
      the relationship involves different aspects in the two cases. 

PMID- 25999894
TI  - Emotional interference-based forgetting in short-term memory. Cognitive
      inhibition of pleasant but not unpleasant biologically relevant distractors.
AB  - Emotional stimuli automatically recruit attentional resources. Although this
      usually brings more adaptive responses, it may suppose a disadvantage when
      emotional information is task-irrelevant and should be ignored. Previous studies
      have shown how emotional stimuli with a negative content exert a greater
      interference than neutral stimuli during a concurrent working memory (WM) task.
      However, the impact of positively valenced stimuli as interference has not been
      addressed to date. In three experiments and one re-analysis we explore the impact
      of pleasant and unpleasant emotional distractors during WM maintenance. The
      results suggest that our cognitive control can cope with the interference posed
      by pleasant distractors as well as with the interference posed by neutral
      stimuli. However, unpleasant distractors are harder to control in the context of
      WM maintenance. As unpleasant stimuli usually convey relevant information that we
      should not to ignore, our executive control seems to be less able to reallocate
      cognitive resources after unpleasant distraction. 

PMID- 25999895
TI  - Influence of being videotaped on the prevalence effect during visual search.
AB  - Video monitoring modifies the task performance of those who are being monitored.
      The current study aims to prevent rare target-detection failures during visual
      search through the use of video monitoring. Targets are sometimes missed when
      their prevalence during visual search is extremely low (e.g., in airport baggage
      screenings). Participants performed a visual search in which they were required
      to discern the presence of a tool in the midst of other objects. The participants
      were monitored via video cameras as they performed the task in one session (the
      videotaped condition), and they performed the same task in another session
      without being monitored (the non-videotaped condition). The results showed that
      fewer miss errors occurred in the videotaped condition, regardless of target
      prevalence. It appears that the decrease in misses in the video monitoring
      condition resulted from a shift in criterion location. Video monitoring is
      considered useful in inducing accurate scanning. It is possible that the
      potential for evaluation involved in being observed motivates the participants to
      perform well and is related to the shift in criterion. 

PMID- 25999896
TI  - Definitely maybe: can unconscious processes perform the same functions as
      conscious processes?
AB  - Hassin recently proposed the "Yes It Can" (YIC) principle to describe the
      division of labor between conscious and unconscious processes in human cognition.
      According to this principle, unconscious processes can carry out every
      fundamental high-level cognitive function that conscious processes can perform.
      In our commentary, we argue that the author presents an overly idealized review
      of the literature in support of the YIC principle. Furthermore, we point out that
      the dissimilar trends observed in social and cognitive psychology, with respect
      to published evidence of strong unconscious effects, can better be explained by
      the way how awareness is defined and measured in both research fields. Finally,
      we show that the experimental paradigm chosen by Hassin to rule out remaining
      objections against the YIC principle is unsuited to verify the new default notion
      that all high-level cognitive functions can unfold unconsciously. 

PMID- 25999897
TI  - Commentary: Olfactory aversive conditioning during sleep reduces cigarette
      smoking behavior.

PMID- 25999898
TI  - Indicators of satisfaction in clickers-aided EFL class.
AB  - How to identify whether students are satisfied with clickers-aided EFL class
      might be largely a mystery for most researchers since satisfaction is deeply
      hidden in human psychology which is subtle and intangible. This study, by using
      bivariate correlation analysis and structural equation modeling, survey scales
      claimed both valid and internally consistent, and data collected from randomly
      selected 227 participants, explored the indicators of satisfaction in clickers
      aided EFL class, together with gender differences in the indicators. It was
      concluded that satisfaction was positively correlated with interaction, self
      efficacy and self-regulation in clickers-aided EFL class without statistically
      significant gender differences. Furthermore, interaction, self-efficacy and self
      regulation were mutually and significantly correlated. Although indicators of
      satisfaction might not be limited to these three factors, the findings should be
      helpful to future researchers who desire to determine whether users are satisfied
      with the polling technology. Then teachers could decide what teaching style and
      contents should be adopted. In order to satisfy users of clickers, future
      lecturing might be designed to promote peer interaction, self-efficacy and self
      regulation. 

PMID- 25999899
TI  - Foreign language comprehension achievement: insights from the cognate
      facilitation effect.
AB  - Numerous studies have shown that the native language influences foreign word
      recognition and that this influence is modulated by the proficiency in the non
      native language. Here we explored how the degree of reliance on cross-language
      similarity (as measured by the cognate facilitation effect) together with other
      domain-general cognitive factors contribute to reading comprehension achievement
      in a non-native language at different stages of the learning process. We tested
      two groups of native speakers of Spanish learning English at elementary and
      intermediate levels in an academic context. A regression model approach showed
      that domain-general cognitive skills are good predictors of second language
      reading achievement independently of the level of proficiency. Critically, we
      found that individual differences in the degree of reliance on the native
      language predicted foreign language reading achievement, showing a markedly
      different pattern between proficiency groups. At lower levels of proficiency the
      cognate facilitation effect was positively related with reading achievement,
      while this relation became negative at intermediate levels of foreign language
      learning. We conclude that the link between native- and foreign-language lexical
      representations helps participants at initial stages of the learning process,
      whereas it is no longer the case at intermediate levels of proficiency, when
      reliance on cross-language similarity is inversely related to successful non
      native reading achievement. Thus, at intermediate levels of proficiency strong
      and direct mappings from the non-native lexical forms to semantic concepts are
      needed to achieve good non-native reading comprehension, in line with the
      premises of current models of bilingual lexico-semantic organization. 

PMID- 25999900
TI  - Grammatical number processing and anticipatory eye movements are not tightly
      coordinated in English spoken language comprehension.
AB  - Recent studies of eye movements in world-situated language comprehension have
      demonstrated that rapid processing of morphosyntactic information - e.g.,
      grammatical gender and number marking - can produce anticipatory eye movements to
      referents in the visual scene. We investigated how type of morphosyntactic
      information and the goals of language users in comprehension affected eye
      movements, focusing on the processing of grammatical number morphology in English
      speaking adults. Participants' eye movements were recorded as they listened to
      simple English declarative (There are the lions.) and interrogative (Where are
      the lions?) sentences. In Experiment 1, no differences were observed in speed to
      fixate target referents when grammatical number information was informative
      relative to when it was not. The same result was obtained in a speeded task
      (Experiment 2) and in a task using mixed sentence types (Experiment 3). We
      conclude that grammatical number processing in English and eye movements to
      potential referents are not tightly coordinated. These results suggest limits on
      the role of predictive eye movements in concurrent linguistic and scene
      processing. We discuss how these results can inform and constrain predictive
      approaches to language processing. 

PMID- 25999901
TI  - Stressful task increases drive for thinness and bulimia: a laboratory study.
AB  - The scientific literature has suggested that stress undergirds the development of
      eating disorders (ED). Therefore, this study explored whether laboratory induced
      stress increases self-reported drive for thinness and bulimic symptoms measured
      via self-report. The relationship between control, perfectionism, stress, and
      cognition related to ED was examined using correlational methodology. Eighty-six
      participants completed an experimental task using a personal computer (PC). All
      individuals completed a battery of tests before and after the stressful task.
      Analyses showed a significant statistical increase in average scores on the drive
      for thinness and bulimia measured before and after a stressful task, and path
      analysis revealed two different cognitive models for the mechanism leading to
      drive for thinness and bulimia. These findings suggest that stress is an
      important factor in the development of the drive for thinness and bulimia. 

PMID- 25999902
TI  - Asian infants show preference for own-race but not other-race female faces: the
      role of infant caregiving arrangements.
AB  - Previous studies have reported that 3- to 4-month-olds show a visual preference
      for faces of the same gender as their primary caregiver (e.g., Quinn et al.,
      2002). In addition, this gender preference has been observed for own-race faces,
      but not for other-race faces (Quinn et al., 2008). However, most of the studies
      of face gender preference have focused on infants at 3-4 months. Development of
      gender preference in later infancy is still unclear. Moreover, all of these
      studies were conducted with Caucasian infants from Western countries. It is thus
      unknown whether a gender preference that is limited to own-race faces can be
      generalized to infants from other racial groups and different cultures with
      distinct caregiving practices. The current study investigated the face gender
      preferences of Asian infants presented with male versus female face pairs from
      Asian and Caucasian races at 3, 6, and 9 months and the role of caregiving
      arrangements in eliciting those preferences. The results showed an own-race
      female face preference in 3- and 6-month-olds, but not in 9-month-olds. Moreover,
      the downturn in the female face preference correlated with the cumulative male
      face experience obtained in caregiving practices. In contrast, no gender
      preference or correlation between gender preference and face experience was found
      for other-race Caucasian faces at any age. The data indicate that the face gender
      preference is not specifically rooted in Western cultural caregiving practices.
      In addition, the race dependency of the effect previously observed for Caucasian
      infants reared by Caucasian caregivers looking at Caucasian but not Asian faces
      extends to Asian infants reared by Asian caregivers looking at Asian but not
      Caucasian faces. The findings also provide additional support for an experiential
      basis for the gender preference, and in particular suggest that cumulative male
      face experience plays a role in inducing a downturn in the preference in older
      infants. 

PMID- 25999903
TI  - Measuring the cognitive resources consumed per second for real-time lie
      production and recollection: a dual-tasking paradigm.
AB  - This research report presents a novel method of dual-tasking lie-detection. Novel
      software "Follow Me" was invented for a concurrent eye-hand coordination task
      during truth-telling/lying. Undergraduate participants were instructed to tell
      truths on questions about undergraduate school whereas they were instructed to
      tell lies on interview questions about graduate school, pretending they were
      graduate students. Throughout the experiment, they operated the "Follow Me"
      software: moving the mouse pointer to follow a randomly-moving dot on a computer
      screen. The distance between the mouse pointer tip and the dot center was
      measured by the software every 50 ms. Frequency of distance fluctuation was
      analyzed as the index of cognitive effort consumed per second (i.e., "degree of
      cognitive effort"). The results revealed that the dominant frequency of distance
      fluctuation was significantly lower during encoding than during retrieving
      responses; and lower during lying than truth-telling. Thus, dominant frequency of
      distance fluctuation may be an effective index of cognitive effort. Moreover,
      both encoding and retrieving bald-faced lies were more cognitively effortful than
      truth-telling. This novel definition and measurement of degree of cognitive
      effort may contribute to the research field of deception as well as to many other
      fields in social cognition. 

PMID- 25999904
TI  - Cognitive spare capacity: evaluation data and its association with comprehension
      of dynamic conversations.
AB  - It is well-established that communication involves the working memory system,
      which becomes increasingly engaged in understanding speech as the input signal
      degrades. The more resources allocated to recovering a degraded input signal, the
      fewer resources, referred to as cognitive spare capacity (CSC), remain for higher
      level processing of speech. Using simulated natural listening environments, the
      aims of this paper were to (1) evaluate an English version of a recently
      introduced auditory test to measure CSC that targets the updating process of the
      executive function, (2) investigate if the test predicts speech comprehension
      better than the reading span test (RST) commonly used to measure working memory
      capacity, and (3) determine if the test is sensitive to increasing the number of
      attended locations during listening. In Experiment I, the CSC test was presented
      using a male and a female talker, in quiet and in spatially separated babble- and
      cafeteria-noises, in an audio-only and in an audio-visual mode. Data collected on
      21 listeners with normal and impaired hearing confirmed that the English version
      of the CSC test is sensitive to population group, noise condition, and clarity of
      speech, but not presentation modality. In Experiment II, performance by 27 normal
      hearing listeners on a novel speech comprehension test presented in noise was
      significantly associated with working memory capacity, but not with CSC.
      Moreover, this group showed no significant difference in CSC as the number of
      talker locations in the test increased. There was no consistent association
      between the CSC test and the RST. It is recommended that future studies
      investigate the psychometric properties of the CSC test, and examine its
      sensitivity to the complexity of the listening environment in participants with
      both normal and impaired hearing. 

PMID- 25999906
TI  - The combination of perception of other individuals and exogenous manipulation of
      arousal enhances social facilitation as an aftereffect: re-examination of
      Zajonc's drive theory.
AB  - Zajonc's drive theory postulates that arousal enhanced through the perception of
      the presence of other individuals plays a crucial role in social facilitation
      (Zajonc, 1965). Here, we conducted two experiments to examine whether the
      elevation of arousal through a stepping exercise performed in front of others as
      an exogenous factor causes social facilitation of a cognitive task in a condition
      where the presence of others does not elevate the arousal level. In the main
      experiment, as an "aftereffect of social stimulus," we manipulated the presence
      or absence of others and arousal enhancement before participants conducted the
      primary cognitive task. The results showed that the strongest social facilitation
      was induced by the combination of the perception of others and arousal
      enhancement. In a supplementary experiment, we manipulated these factors by
      adding the presence of another person during the task. The results showed that
      the effect of the presence of the other during the primary task is enough on its
      own to produce facilitation of task performance regardless of the arousal
      enhancement as an aftereffect of social stimulus. Our study therefore extends the
      framework of Zajonc's drive theory in that the combination of the perception of
      others and enhanced arousal as an "aftereffect" was found to induce social
      facilitation especially when participants did not experience the presence of
      others while conducting the primary task. 

PMID- 25999905
TI  - Somatic, but not cognitive-affective, symptoms are associated with reduced heart
      rate variability in individuals with dysphoria.
AB  - BACKGROUND: Somatic, but not cognitive-affective, symptoms of depression have
      been associated with reduced heart rate variability (HRV), and with poor
      prognosis in cardiovascular patients. However, factors concomitant with
      cardiovascular diseases may confound the relationship between somatic symptoms of
      depression and reduced HRV. Therefore, this study examined whether reduced HRV
      was differentially associated with cognitive-affective and somatic symptoms of
      depression in medically healthy individuals with and without dysphoria. METHODS:
      Self-reported cognitive-affective and somatic symptoms as measured with the Beck
      Depression Inventory-II questionnaire and time and frequency domain parameters of
      HRV were collected in 62 medically healthy individuals, of whom 25 with and 37
      without dysphoria. RESULTS: Somatic, but not cognitive-affective, symptoms of
      depression were inversely associated with SD of NN intervals (beta = -0.476, p <
      0.05), number of interval differences of successive NN intervals greater than 50
      ms (NN50; beta = -0.498, p < 0.03), and HRV total power (beta = -0.494, p < 0.04)
      in the group with dysphoria, after controlling for sex, anxiety, and lifestyle
      factors. Cognitive-affective and somatic symptoms were not related to any of the
      HRV parameters in the group without dysphoria (all ps > 0.24). CONCLUSION: By
      showing that the relationship between somatic depressive symptoms and reduced HRV
      extends to medically healthy individuals with dysphoria, the present findings
      suggest that this association is independent of factors concomitant with
      cardiovascular diseases. The present study also suggests that individuals with
      somatic rather than cognitive-affective subsets of depressive symptoms may be at
      greater risk for developing cardiovascular diseases.

PMID- 25999907
TI  - How best to study the function of consciousness?

PMID- 25999909
TI  - Could cognitive estimation ability be a measure of cognitive reserve?

PMID- 25999908
TI  - EEG oscillations during sleep and dream recall: state- or trait-like individual
      differences?
AB  - Dreaming represents a peculiar form of cognitive activity during sleep. On the
      basis of the well-known relationship between sleep and memory, there has been a
      growing interest in the predictive role of human brain activity during sleep on
      dream recall. Neuroimaging studies indicate that rapid eye movement (REM) sleep
      is characterized by limbic activation and prefrontal cortex deactivation. This
      pattern could explain the presence of emotional contents in dream reports.
      Furthermore, the morphoanatomical measures of amygdala and hippocampus predict
      some features of dream contents (bizarreness, vividness, and emotional load).
      More relevant for a general view of dreaming mechanisms, empirical data from
      neuropsychological and electroencephalographic (EEG) studies support the
      hypothesis that there is a sort of continuity between the neurophysiological
      mechanisms of encoding and retrieval of episodic memories across sleep and
      wakefulness. A notable overlap between the electrophysiological mechanisms
      underlying emotional memory formation and some peculiar EEG features of REM sleep
      has been suggested. In particular, theta (5-8 Hz) EEG oscillations on frontal
      regions in the pre-awakening sleep are predictive of dream recall, which
      parallels the predictive relation during wakefulness between theta activity and
      successful retrieval of episodic memory. Although some observations support an
      interpretation more in terms of an intraindividual than interindividual
      mechanism, the existing empirical evidence still precludes from definitely
      disentangling if this relation is explained by state- or trait-like differences. 

PMID- 25999910
TI  - When physics meets biology: low and high-velocity penetration, blunt impact, and
      blast injuries to the brain.
AB  - The incidence of traumatic brain injuries (TBI) in the US has reached epidemic
      proportions with well over 2 million new cases reported each year. TBI can occur
      in both civilians and warfighters, with head injuries occurring in both combat
      and non-combat situations from a variety of threats, including ballistic
      penetration, acceleration, blunt impact, and blast. Most generally, TBI is a
      condition in which physical loads exceed the capacity of brain tissues to absorb
      without injury. More specifically, TBI results when sufficient external force is
      applied to the head and is subsequently converted into stresses that must be
      absorbed or redirected by protective equipment. If the stresses are not
      sufficiently absorbed or redirected, they will lead to damage of extracranial
      soft tissue and the skull. Complex interactions and kinematics of the head, neck
      and jaw cause strains within the brain tissue, resulting in structural,
      anatomical damage that is characteristic of the inciting insult. This mechanical
      trauma then initiates a neuro-chemical cascade that leads to the functional
      consequences of TBI, such as cognitive impairment. To fully understand the
      mechanisms by which TBI occurs, it is critically important to understand the
      effects of the loading environments created by these threats. In the following, a
      review is made of the pertinent complex loading conditions and how these loads
      cause injury. Also discussed are injury thresholds and gaps in knowledge, both of
      which are needed to design improved protective systems. 

PMID- 25999911
TI  - CSF Neurofilament Light Chain but not FLT3 Ligand Discriminates Parkinsonian
      Disorders.
AB  - The differentiation between multiple system atrophy (MSA) and Parkinson's disease
      (PD) is difficult, particularly in early disease stages. Therefore, we aimed to
      evaluate the diagnostic value of neurofilament light chain (NFL), fms-like
      tyrosine kinase ligand (FLT3L), and total tau protein (t-tau) in cerebrospinal
      fluid (CSF) as biomarkers to discriminate MSA from PD. Using commercially
      available enzyme-linked immunosorbent assays, we measured CSF levels of NFL,
      FLT3L, and t-tau in a discovery cohort of 36 PD patients, 27 MSA patients, and 57
      non-neurological controls and in a validation cohort of 32 PD patients, 25 MSA
      patients, 15 PSP patients, 5 CBS patients, and 56 non-neurological controls. Cut
      offs obtained from individual assays and binary logistic regression models
      developed from combinations of biomarkers were assessed. CSF levels of NFL were
      substantially increased in MSA and discriminated between MSA and PD with a
      sensitivity of 74% and specificity of 92% (AUC = 0.85) in the discovery cohort
      and with 80% sensitivity and 97% specificity (AUC = 0.94) in the validation
      cohort. FLT3L levels in CSF were significantly lower in both PD and MSA compared
      to controls in the discovery cohort, but not in the validation cohort. t-tau
      levels were significantly higher in MSA than PD and controls. Addition of either
      FLT3L or t-tau to NFL did not improve discrimination of PD from MSA above NFL
      alone. Our findings show that increased levels of NFL in CSF offer clinically
      relevant, high accuracy discrimination between PD and MSA. 

PMID- 25999912
TI  - A theoretical study on seasonality.
AB  - In addition to being endogenous, a circadian system must be able to communicate
      with the outside world and align its rhythmicity to the environment. As a result
      of such alignment, external Zeitgebers can entrain the circadian system.
      Entrainment expresses itself in coinciding periods of the circadian oscillator
      and the Zeitgeber and a stationary phase difference between them. The range of
      period mismatches between the circadian system and the Zeitgeber that Zeitgeber
      can overcome to entrain the oscillator is called an entrainment range. The width
      of the entrainment range usually increases with increasing Zeitgeber strength,
      resulting in a wedge-like Arnold tongue. This classical view of entrainment does
      not account for the effects of photoperiod on entrainment. Zeitgebers with
      extremely small or large photoperiods are intuitively closer to constant
      environments than equinoctial Zeitgebers and hence are expected to produce a
      narrower entrainment range. In this paper, we present theoretical results on
      entrainment under different photoperiods. We find that in the photoperiod
      detuning parameter plane, the entrainment zone is shaped in the form of a skewed
      onion. The bottom and upper points of the onion are given by the free-running
      periods in DD and LL, respectively. The widest entrainment range is found near
      photoperiods of 50%. Within the onion, we calculated the entrainment phase that
      varies over a range of 12 h. The results of our theoretical study explain the
      experimentally observed behavior of the entrainment phase in dependence on the
      photoperiod. 

PMID- 25999915
TI  - Igf-I influences everolimus activity in medullary thyroid carcinoma.
AB  - CONTEXT: Medullary thyroid carcinoma (MTC) is a rare tumor originating from
      thyroid parafollicular C cells. It has been previously demonstrated that insulin
      like growth factor I (IGF-I) protects MTC from the effects of antiproliferative
      drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects
      in a human MTC cell line, TT, and in two human MTC primary cultures. OBJECTIVE:
      To verify whether IGF-I may influence the effects of everolimus in a group of
      human MTC primary cultures. DESIGN: We collected 18 MTCs that were dispersed in
      primary cultures, treated without or with 10 nM-1 MUM everolimus and/or 50 nM IGF
      I. Cell viability was evaluated after 48 h, and calcitonin (CT) secretion was
      assessed after a 6 h incubation. IGF-I receptor downstream signaling protein
      expression profile was also investigated. RESULTS: Everolimus significantly
      reduced cell viability in eight MTC [by ~20%; P < 0.01 vs. control; everolimus
      responders (E-R) MTCs], while cell viability did not change in 10 MTCs
      [everolimus-non-responders (E-NR) MTCs]. In E-R MTCs, IGF-I blocked the
      antiproliferative effects of everolimus that did not affect CT secretion, but
      blocked the stimulatory effects of IGF-I on this parameter. IGF-I receptor
      downstream signaling proteins were expressed at higher levels in E-NR MTC as
      compared to E-R MTCs. CONCLUSION: IGF-I protects a subset of MTC primary cultures
      from the antiproliferative effects of everolimus and stimulates CT secretion by
      an mTOR mediated pathway that, in turn, may represent a therapeutic target in the
      treatment of aggressive MTCs.

PMID- 25999914
TI  - Transcriptional control of mitosis: deregulation and cancer.
AB  - Research over the past few decades has well established the molecular functioning
      of mitosis. Deregulation of these functions has also been attributed to the
      generation of aneuploidy in different tumor types. Numerous studies have given
      insight into the regulation of mitosis by cell cycle specific proteins. Optimum
      abundance of these proteins is pivotal to timely execution of mitosis. Aberrant
      expressions of these mitotic proteins have been reported in different cancer
      types. Several post-transcriptional mechanisms and their interplay have
      subsequently been identified that control the level of mitotic proteins. However,
      to date, infrequent incidences of cancer-associated mutations have been reported
      for the genes expressing these proteins. Therefore, altered expression of these
      mitotic regulators in tumor samples can largely be attributed to transcriptional
      deregulation. This review discusses the biology of transcriptional control for
      mitosis and evaluates its role in the generation of aneuploidy and tumorigenesis.

PMID- 25999913
TI  - Nuclear receptors and endocrine disruptors in fetal and neonatal testes: a gapped
      landscape.
AB  - During the last decades, many studies reported that male reproductive disorders
      are increasing among humans. It is currently acknowledged that these
      abnormalities can result from fetal exposure to environmental chemicals that are
      progressively becoming more concentrated and widespread in our environment. Among
      the chemicals present in the environment (air, water, food, and many consumer
      products), several can act as endocrine disrupting compounds (EDCs), thus
      interfering with the endocrine system. Phthalates, bisphenol A (BPA), and
      diethylstilbestrol (DES) have been largely incriminated, particularly during the
      fetal and neonatal period, due to their estrogenic and/or anti-androgenic
      properties. Indeed, many epidemiological and experimental studies have
      highlighted their deleterious impact on fetal and neonatal testis development. As
      EDCs can affect many different genomic and non-genomic pathways, the mechanisms
      underlying the adverse effects of EDC exposure are difficult to elucidate. Using
      literature data and results from our laboratory, in the present review, we
      discuss the role of classical nuclear receptors (genomic pathway) in the fetal
      and neonatal testis response to EDC exposure, particularly to phthalates, BPA,
      and DES. Among the nuclear receptors, we focused on some of the most likely
      candidates, such as peroxisome-proliferator activated receptor (PPAR), androgen
      receptor (AR), estrogen receptors (ERalpha and beta), liver X receptors (LXR),
      and small heterodimer partner (SHP). First, we describe the expression and
      potential functions (based on data from studies using receptor agonists and mouse
      knockout models) of these nuclear receptors in the developing testis. Then, for
      each EDC studied, we summarize the main evidences indicating that the reprotoxic
      effect of each EDC under study is mediated through a specific nuclear
      receptor(s). We also point-out the involvement of other receptors and nuclear
      receptor-independent pathways. 

PMID- 25999916
TI  - New directions for the treatment of adrenal insufficiency.
AB  - Adrenal disease, whether primary, caused by defects in the hypothalamic-pituitary
      adrenal (HPA) axis, or secondary, caused by defects outside the HPA axis, usually
      results in adrenal insufficiency, which requires lifelong daily replacement of
      corticosteroids. However, this kind of therapy is far from ideal as physiological
      demand for steroids varies considerably throughout the day and increases during
      periods of stress. The development of alternative curative strategies is
      therefore needed. In this review, we describe the latest technologies aimed at
      either isolating or generating de novo cells that could be used for novel,
      regenerative medicine application in the adrenocortical field. 

PMID- 25999917
TI  - Characterization of Francisella tularensis Schu S4 mutants identified from a
      transposon library screened for O-antigen and capsule deficiencies.
AB  - The lipopolysaccharide (LPS) and O-antigen polysaccharide capsule structures of
      Francisella tularensis play significant roles in helping these highly virulent
      bacteria avoid detection within a host. We previously created pools of F.
      tularensis mutants that we screened to identify strains that were not reactive to
      a monoclonal antibody to the O-antigen capsule. To follow up previously published
      work, we characterize further seven of the F. tularensis Schu S4 mutant strains
      identified by our screen. These F. tularensis strains carry the following
      transposon mutations: FTT0846::Tn5, hemH::Tn5, wbtA::Tn5, wzy::Tn5,
      FTT0673p/prsA::Tn5, manB::Tn5, or dnaJ::Tn5. Each of these strains displayed
      sensitivity to human serum, to varying degrees, when compared to wild-type F.
      tularensis Schu S4. By Western blot, only FTT0846::Tn5, wbtA::Tn5, wzy::Tn5, and
      manB::Tn5 strains did not react to the capsule and LPS O-antigen antibody 11B7,
      although the wzy::Tn5 strain did have a single O-antigen reactive band that was
      detected by the FB11 monoclonal antibody. Of these strains, manB::Tn5 and FTT0846
      appear to have LPS core truncations, whereas wbtA::Tn5 and wzy::Tn5 had LPS core
      structures that are similar to the parent F. tularensis Schu S4. These strains
      were also shown to have poor growth within human monocyte derived macrophages
      (MDMs) and bone marrow derived macrophages (BMDMs). We examined the virulence of
      these strains in mice, following intranasal challenge, and found that each was
      attenuated compared to wild type Schu S4. Our results provide additional strong
      evidence that LPS and/or capsule are F. tularensis virulence factors that most
      likely function by providing a stealth shield that prevents the host immune
      system from detecting this potent pathogen. 

PMID- 25999918
TI  - Antibacterial activity of endophytic fungi from leaves of Indigofera suffruticosa
      Miller (Fabaceae).
AB  - Endophytic fungi were isolated from healthy leaves of Indigofera suffruticosa
      Miller, a medicinal plant found in Brazil which is used in folk medicine to treat
      various diseases. Among 65 endophytic fungi isolated, 18 fungi showed activity
      against at least one tested microorganism in preliminary screening, and the best
      results were obtained with Nigrospora sphaerica (URM-6060) and Pestalotiopsis
      maculans (URM-6061). After fermentation in liquid media and in semisolid media,
      only N. sphaerica demonstrated antibacterial activity (in Potato Dextrose Broth
      PDB and in semisolid rice culture medium). In the next step, a methanolic extract
      from rice culture medium (NsME) and an ethyl acetate extract (NsEAE) from the
      supernatant of PDB were prepared and both exhibited antimicrobial activity
      against Gram-negative and Gram-positive bacteria. The best result was observed
      against Staphylococcus aureus, with minimum inhibitory concentration (MIC) and
      minimum bactericidal concentration (MBC) values of 1.56 mg/mL and 6.25 mg/mL,
      respectively, for NsME and MIC and MBC values of 0.39 mg/mL and 3.12 mg/mL,
      respectively, for NsEAE. This study is the first report about the antimicrobial
      activity of endophytic fungi residing in I. suffruticosa leaves, in which the
      fungus N. sphaerica demonstrated the ability to produce bioactive agents with
      pharmaceutical potential, and may provide a new lead in the pursuit of new
      biological sources of drug candidates. 

PMID- 25999919
TI  - Phenotypic and transcriptional profiling in Entamoeba histolytica reveal costs to
      fitness and adaptive responses associated with metronidazole resistance.
AB  - Antimicrobial chemotherapy is critical in the fight against infectious diseases
      caused by Entamoeba histolytica. Among the drugs available for the treatment of
      amebiasis, metronidazole (MTZ) is considered the drug of choice. Recently, in
      vitro studies have described MTZ resistance and the potential mechanisms
      involved. Costs to fitness and adaptive responses associated with resistance,
      however, have not been investigated. In this study we generated an HM-1 derived
      strain resistant to 12 MUM MTZ (MTZR). We examined its phenotypic and
      transcriptional profile to determine the consequences and mRNA level changes
      associated with MTZ resistance. Our results indicated increased cell size and
      granularity, and decreased rates in cell division, adhesion, phagocytosis,
      cytopathogenicity, and glucose consumption. Transcriptome analysis revealed 142
      differentially expressed genes in MTZR. In contrast to other MTZ resistant
      parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but
      showed increased expression of genes for a hypothetical protein (HP1) and several
      iron-sulfur flavoproteins, and downregulation of genes for leucine-rich proteins.
      Fisher's exact test showed 24 significantly enriched GO terms in MTZR, and a 3
      way comparison of modulated genes in MTZR against those of MTZR cultured without
      MTZ and HM-1 cultured with MTZ, showed that 88 genes were specific to MTZR.
      Overall, our findings suggested that MTZ resistance is associated with specific
      transcriptional changes and decreased parasite virulence. 

PMID- 25999920
TI  - Chemolithoautotrophic arsenite oxidation by a thermophilic Anoxybacillus
      flavithermus strain TCC9-4 from a hot spring in Tengchong of Yunnan, China.
AB  - A new facultative chemolithoautotrophic arsenite (As(III))-oxidizing bacterium
      TCC9-4 was isolated from a hot spring microbial mat in Tengchong of Yunnan,
      China. This strain could grow with As(III) as an energy source, CO2-HCO3 (-) as a
      carbon source and oxygen as the electron acceptor in a minimal salts medium.
      Under chemolithoautotrophic conditions, more than 90% of 100 mg/L As(III) could
      be oxidized by the strain TCC9-4 in 36 h. Temperature was an important
      environmental factor that strongly influenced the As(III) oxidation rate and
      As(III) oxidase (Aio) activity; the highest Aio activity was found at the
      temperature of 40?C. Addition of 0.01% yeast extract enhanced the growth
      significantly, but delayed the As(III) oxidation. On the basis of 16S rRNA
      phylogenetic sequence analysis, strain TCC9-4 was identified as Anoxybacillus
      flavithermus. To our best knowledge, this is the first report of arsenic (As)
      oxidation by A. flavithermus. The Aio gene in TCC9-4 might be quite novel
      relative to currently known gene sequences. The results of this study expand our
      current understanding of microbially mediated As oxidation in hot springs. 

PMID- 25999921
TI  - Microbial food web components, bulk metabolism, and single-cell physiology of
      piconeuston in surface microlayers of high-altitude lakes.
AB  - Sharp boundaries in the physical environment are usually associated with abrupt
      shifts in organism abundance, activity, and diversity. Aquatic surface
      microlayers (SML) form a steep gradient between two contrasted environments, the
      atmosphere and surface waters, where they regulate the gas exchange between both
      environments. They usually harbor an abundant and active microbial life: the
      neuston. Few ecosystems are subjected to such a high UVR regime as high altitude
      lakes during summer. Here, we measured bulk estimates of heterotrophic activity,
      community structure and single-cell physiological properties by flow cytometry in
      19 high-altitude remote Pyrenean lakes and compared the biological processes in
      the SML with those in the underlying surface waters. Phototrophic picoplankton
      (PPP) populations, were generally present in high abundances and in those lakes
      containing PPP populations with phycoerythrin (PE), total PPP abundance was
      higher at the SML. Heterotrophic nanoflagellates (HNF) were also more abundant in
      the SML. Bacteria in the SML had lower leucine incorporation rates, lower
      percentages of "live" cells, and higher numbers of highly-respiring cells, likely
      resulting in a lower growth efficiency. No simple and direct linear relationships
      could be found between microbial abundances or activities and environmental
      variables, but factor analysis revealed that, despite their physical proximity,
      microbial life in SML and underlying waters was governed by different and
      independent processes. Overall, we demonstrate that piconeuston in high altitude
      lakes has specific features different from those of the picoplankton, and that
      they are highly affected by potential stressful environmental factors, such as
      high UVR radiation. 

PMID- 25999922
TI  - Getting a hold on archaeal type IV pili: an expanding repertoire of cellular
      appendages implicates complex regulation and diverse functions.

PMID- 25999923
TI  - Examining the virulence of Candida albicans transcription factor mutants using
      Galleria mellonella and mouse infection models.
AB  - The aim of the present study was to identify Candida albicans transcription
      factors (TFs) involved in virulence. Although mice are considered the gold
      standard model to study fungal virulence, mini-host infection models have been
      increasingly used. Here, barcoded TF mutants were first screened in mice by pools
      of strains and fungal burdens (FBs) quantified in kidneys. Mutants of unannotated
      genes which generated a kidney FB significantly different from that of wild-type
      were selected and individually examined in Galleria mellonella. In addition,
      mutants that could not be detected in mice were also tested in G. mellonella.
      Only 25% of these mutants displayed matching phenotypes in both hosts,
      highlighting a significant discrepancy between the two models. To address the
      basis of this difference (pool or host effects), a set of 19 mutants tested in G.
      mellonella were also injected individually into mice. Matching FB phenotypes were
      observed in 50% of the cases, highlighting the bias due to host effects. In
      contrast, 33.4% concordance was observed between pool and single strain
      infections in mice, thereby highlighting the bias introduced by the "pool
      effect." After filtering the results obtained from the two infection models,
      mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were
      subsequently tested in both hosts to validate previous results. The MBF1 mutant
      showed impaired infection in both models, while the ZCF6 mutant was only
      significant in mice infections. The two mutants showed no obvious in vitro
      phenotypes compared with the wild-type, indicating that these genes might be
      specifically involved in in vivo adapt. 

PMID- 25999924
TI  - Vancomycin modifies the expression of the agr system in multidrug-resistant
      Staphylococcus aureus clinical isolates.
AB  - Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and
      causes a wide variety of diseases. Two interacting regulatory systems called agr
      (accessory gene regulator) and sar (staphylococcal accessory regulator) are
      involved in the regulation of virulence factors. The aim of this study was to
      evaluate the effect of vancomycin on hld and spa gene expression during the
      exponential and post-exponential growth phases in multidrug-resistant (MDR) S.
      aureus. METHODS: Antibiotic susceptibility was evaluated by the standard
      microdilution method. The phylogenetic profile was obtained by pulsed-field gel
      electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette
      chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The
      expression levels of hld and spa were analyzed by reverse transcription-PCR. An
      enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and
      biofilm formation was analyzed via crystal violet staining. RESULTS: In total,
      60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR
      S. aureus isolates were distributed in subcluster 10, with >90% similarity among
      them. In the isolates of this subcluster, a high prevalence (100%) for the agrII
      and the cassette SCCmec II polymorphisms was found. Our data showed significant
      increases in hld expression during the post-exponential phase in the presence and
      absence of vancomycin. Significant increases in spa expression, protein A
      production and biofilm formation were observed during the post-exponential phase
      when the MDR S. aureus isolates were challenged with vancomycin. CONCLUSION: The
      polymorphism agrII, which is associated with nosocomial isolates, was the most
      prevalent polymorphism in MDR S. aureus. Additionally, under our study
      conditions, vancomycin modified hld and spa expression in these clinical
      isolates. Therefore, vancomycin may regulate alternative systems that jointly
      participate in the regulation of these virulence factors.

PMID- 25999925
TI  - Motif-independent de novo detection of secondary metabolite gene clusters-toward
      identification from filamentous fungi.
AB  - Secondary metabolites are produced mostly by clustered genes that are essential
      to their biosynthesis. The transcriptional expression of these genes is often
      cooperatively regulated by a transcription factor located inside or close to a
      cluster. Most of the secondary metabolism biosynthesis (SMB) gene clusters
      identified to date contain so-called core genes with distinctive sequence
      features, such as polyketide synthase (PKS) and non-ribosomal peptide synthetase
      (NRPS). Recent efforts in sequencing fungal genomes have revealed far more SMB
      gene clusters than expected based on the number of core genes in the genomes.
      Several bioinformatics tools have been developed to survey SMB gene clusters
      using the sequence motif information of the core genes, including SMURF and
      antiSMASH. More recently, accompanied by the development of sequencing techniques
      allowing to obtain large-scale genomic and transcriptomic data, motif-independent
      prediction methods of SMB gene clusters, including MIDDAS-M, have been developed.
      Most these methods detect the clusters in which the genes are cooperatively
      regulated at transcriptional levels, thus allowing the identification of novel
      SMB gene clusters regardless of the presence of the core genes. Another type of
      the method, MIPS-CG, uses the characteristics of SMB genes, which are highly
      enriched in non-syntenic blocks (NSBs), enabling the prediction even without
      transcriptome data although the results have not been evaluated in detail.
      Considering that large portion of SMB gene clusters might be sufficiently
      expressed only in limited uncommon conditions, it seems that prediction of SMB
      gene clusters by bioinformatics and successive experimental validation is an only
      way to efficiently uncover hidden SMB gene clusters. Here, we describe and
      discuss possible novel approaches for the determination of SMB gene clusters that
      have not been identified using conventional methods. 

PMID- 25999926
TI  - Microbial lipid and amino sugar responses to long-term simulated global
      environmental changes in a California annual grassland.
AB  - Global environmental change is predicted to have major consequences for carbon
      cycling and the functioning of soil ecosystems. However, we have limited
      knowledge about its impacts on the microorganisms, which act as a "valve" between
      carbon sequestered in soils versus released into the atmosphere. In this study we
      examined microbial response to continuous 9-years manipulation of three global
      change factors (elevated CO2, warming, and nitrogen deposition), singly and in
      combination using two methods: lipid and amino sugar biomarkers at the Jasper
      Ridge Global Change Experiment (JRGCE). The two methods yielded important
      distinctions. There were limited microbial lipid differences, but many
      significant effects for microbial amino sugars. We found that CO2 was not a
      direct factor influencing soil carbon and major amino sugar pools, but had a
      positive impact on bacterial-derived muramic acid. Likewise, warming and nitrogen
      deposition appeared to enrich residues specific to bacteria despite an overall
      depletion in total amino sugars. The results indicate that elevated CO2, warming,
      and nitrogen deposition all appeared to increase bacterial-derived residues, but
      this accumulation effect was far offset by a corresponding decline in fungal
      residues. The sensitivity of microbial residue biomarker amino sugars to warming
      and nitrogen deposition may have implications for our predictions of global
      change impacts on soil stored carbon. 

PMID- 25999927
TI  - Isolation of microorganisms involved in reduction of crystalline iron(III) oxides
      in natural environments.
AB  - Reduction of crystalline Fe(III) oxides is one of the most important electron
      sinks for organic compound oxidation in natural environments. Yet the limited
      number of isolates makes it difficult to understand the physiology and ecological
      impact of the microorganisms involved. Here, two-stage cultivation was
      implemented to selectively enrich and isolate crystalline iron(III) oxide
      reducing microorganisms in soils and sediments. Firstly, iron reducers were
      enriched and other untargeted eutrophs were depleted by 2-years successive
      culture on a crystalline ferric iron oxide (i.e., goethite, lepidocrocite,
      hematite, or magnetite) as electron acceptor. Fifty-eight out of 136 incubation
      conditions allowed the continued existence of microorganisms as confirmed by PCR
      amplification. High-throughput Illumina sequencing and clone library analysis
      based on 16S rRNA genes revealed that the enrichment cultures on each of the
      ferric iron oxides contained bacteria belonging to the Deltaproteobacteria
      (mainly Geobacteraceae), followed by Firmicutes and Chloroflexi, which also
      comprised most of the operational taxonomic units (OTUs) identified. Venn
      diagrams indicated that the core OTUs enriched with all of the iron oxides were
      dominant in the Geobacteraceae while each type of iron oxides supplemented
      selectively enriched specific OTUs in the other phylogenetic groups. Secondly, 38
      enrichment cultures including novel microorganisms were transferred to soluble
      iron(III) containing media in order to stimulate the proliferation of the
      enriched iron reducers. Through extinction dilution-culture and single colony
      isolation, six strains within the Deltaproteobacteria were finally obtained; five
      strains belonged to the genus Geobacter and one strain to Pelobacter. The 16S
      rRNA genes of these isolates were 94.8-98.1% identical in sequence to cultured
      relatives. All the isolates were able to grow on acetate and ferric iron but
      their physiological characteristics differed considerably in terms of growth
      rate. Thus, the novel strategy allowed to enrich and isolate novel iron(III)
      reducers that were able to thrive by reducing crystalline ferric iron oxides. 

PMID- 25999928
TI  - The antimicrobial activity of heterotrophic bacteria isolated from the marine
      sponge Erylus deficiens (Astrophorida, Geodiidae).
AB  - Interest in the study of marine sponges and their associated microbiome has
      increased both for ecological reasons and for their great biotechnological
      potential. In this work, heterotrophic bacteria associated with three specimens
      of the marine sponge Erylus deficiens, were isolated in pure culture,
      phylogenetically identified and screened for antimicrobial activity. The
      isolation of bacteria after an enrichment treatment in heterotrophic medium
      revealed diversity in bacterial composition with only Pseudoalteromonas being
      shared by two specimens. Of the 83 selected isolates, 58% belong to
      Proteobacteria, 23% to Actinobacteria and 19% to Firmicutes. Diffusion agar
      assays for bioactivity screening against four bacterial strains and one yeast,
      revealed that a high number of the isolated bacteria (68.7%) were active,
      particularly against Candida albicans and Vibrio anguillarum. Pseudoalteromonas,
      Microbacterium, and Proteus were the most bioactive genera. After this
      preliminary screening, the bioactive strains were further evaluated in liquid
      assays against C. albicans, Bacillus subtilis and Escherichia coli. Filtered
      culture medium and acetone extracts from three and 5 days-old cultures were
      assayed. High antifungal activity against C. albicans in both aqueous and acetone
      extracts as well as absence of activity against B. subtilis were confirmed.
      Higher levels of activity were obtained with the aqueous extracts when compared
      to the acetone extracts and differences were also observed between the 3 and 5
      day-old extracts. Furthermore, a low number of active strains was observed
      against E. coli. Potential presence of type-I polyketide synthases (PKS-I) and
      non-ribosomal peptide synthetases (NRPSs) genes were detected in 17 and 30
      isolates, respectively. The high levels of bioactivity and the likely presence of
      associated genes suggest that Erylus deficiens bacteria are potential sources of
      novel marine bioactive compounds. 

PMID- 25999929
TI  - Nanosilver induces a non-culturable but metabolically active state in Pseudomonas
      aeruginosa.
AB  - The antimicrobial properties of silver nanoparticles (AgNPs) have raised
      expectations for the protection of medical devices and consumer products against
      biofilms. The effect of silver on bacteria is commonly determined by culture
      dependent methods. It is as yet unknown if silver-exposed bacteria can enter a
      metabolically active but non-culturable state. In this study, the efficacy of
      chemically synthesized AgNPs and silver as silver nitrate (AgNO3) against
      planktonic cells and biofilms of Pseudomonas aeruginosa AdS was investigated in
      microtiter plate assays, using cultural as well as culture-independent methods.
      In liquid medium, AgNPs and AgNO3 inhibited both planktonic growth and biofilm
      formation. The efficacy of AgNPs and AgNO3 against established, 24 h-old biofilms
      and planktonic stationary-phase cells was compared by exposure to silver in
      deionized water. Loss of culturability of planktonic cells was always higher than
      that of the attached biofilms. However, resuspended biofilm cells became more
      susceptible to AgNPs and AgNO3 than attached biofilms. Thus, the physical state
      of bacteria within biofilms rendered them more tolerant to silver compared with
      the planktonic state. Silver-exposed cells that had become unculturable still
      displayed signs of viability: they contained rRNA, determined by fluorescent in
      situ hybridization, as an indicator for potential protein synthesis, maintained
      their membrane integrity as monitored by differential live/dead staining, and
      displayed significant levels of adenosine triphosphate. It was concluded that
      AgNPs and AgNO3 in concentrations at which culturability was inhibited, both
      planktonic and biofilm cells of P. aeruginosa were still intact and metabolically
      active, reminiscent of the viable but non-culturable state known to be induced in
      pathogenic bacteria in response to stress conditions. This observation is
      important for a realistic assessment of the antimicrobial properties of AgNPs. 

PMID- 25999930
TI  - Sterilization of liquid foods by pulsed electric fields-an innovative ultra-high
      temperature process.
AB  - The intention of this study was to investigate the inactivation of endospores by
      a combined thermal and pulsed electric field (PEF) treatment. Therefore, self
      cultivated spores of Bacillus subtilis and commercial Geobacillus
      stearothermophilus spores with certified heat resistance were utilized. Spores of
      both strains were suspended in saline water (5.3 mS cm(-1)), skim milk (0.3% fat;
      5.3 mS cm(-1)) and fresh prepared carrot juice (7.73 mS cm(-1)). The combination
      of moderate preheating (70-90 degrees C) and an insulated PEF-chamber, combined
      with a holding tube (65 cm) and a heat exchanger for cooling, enabled a rapid
      heat up to 105-140 degrees C (measured above the PEF chamber) within 92.2-368.9
      MUs. To compare the PEF process with a pure thermal inactivation, each spore
      suspension was heat treated in thin glass capillaries and D-values from 90 to 130
      degrees C and its corresponding z-values were calculated. For a comparison of the
      inactivation data, F-values for the temperature fields of both processes were
      calculated by using computational fluid dynamics (CFD). A preheating of saline
      water to 70 degrees C with a flow rate of 5 l h(-1), a frequency of 150 Hz and an
      energy input of 226.5 kJ kg(-1), resulted in a measured outlet temperature of 117
      degrees C and a 4.67 log10 inactivation of B. subtilis. The thermal process with
      identical F-value caused only a 3.71 log10 inactivation. This synergism of
      moderate preheating and PEF was even more pronounced for G. stearothermophilus
      spores in saline water. A preheating to 95 degrees C and an energy input of 144
      kJ kg(-1) resulted in an outlet temperature of 126 degrees C and a 3.28 log10
      inactivation, whereas nearly no inactivation (0.2 log10) was achieved during the
      thermal treatment. Hence, the PEF technology was evaluated as an alternative
      ultra-high temperature process. However, for an industrial scale application of
      this process for sterilization, optimization of the treatment chamber design is
      needed to reduce the occurring inhomogeneous temperature fields. 

PMID- 25999931
TI  - Changes in gene expression, cell physiology and toxicity of the harmful
      cyanobacterium Microcystis aeruginosa at elevated CO2.
AB  - Rising CO2 concentrations may have large effects on aquatic microorganisms. In
      this study, we investigated how elevated pCO2 affects the harmful freshwater
      cyanobacterium Microcystis aeruginosa. This species is capable of producing dense
      blooms and hepatotoxins called microcystins. Strain PCC 7806 was cultured in
      chemostats that were shifted from low to high pCO2 conditions. This resulted in a
      transition from a C-limited to a light-limited steady state, with a ~2.7-fold
      increase of the cyanobacterial biomass and ~2.5-fold more microcystin per cell.
      Cells increased their chlorophyll a and phycocyanin content, and raised their
      PSI/PSII ratio at high pCO2. Surprisingly, cells had a lower dry weight and
      contained less carbohydrates, which might be an adaptation to improve the
      buoyancy of Microcystis when light becomes more limiting at high pCO2. Only 234
      of the 4691 genes responded to elevated pCO2. For instance, expression of the
      carboxysome, RuBisCO, photosystem and C metabolism genes did not change
      significantly, and only a few N assimilation genes were expressed differently.
      The lack of large-scale changes in the transcriptome could suit a buoyant species
      that lives in eutrophic lakes with strong CO2 fluctuations very well. However, we
      found major responses in inorganic carbon uptake. At low pCO2, cells were mainly
      dependent on bicarbonate uptake, whereas at high pCO2 gene expression of the
      bicarbonate uptake systems was down-regulated and cells shifted to CO2 and low
      affinity bicarbonate uptake. These results show that the need for high-affinity
      bicarbonate uptake systems ceases at elevated CO2. Moreover, the combination of
      an increased cyanobacterial abundance, improved buoyancy, and higher toxin
      content per cell indicates that rising atmospheric CO2 levels may increase the
      problems associated with the harmful cyanobacterium Microcystis in eutrophic
      lakes. 

PMID- 25999932
TI  - Impacts of dimethyl phthalate on the bacterial community and functions in black
      soils.
AB  - Dimethyl phthalate (DMP), a known endocrine disruptor and one of the phthalate
      esters (PAEs), is a ubiquitous pollutant. Its impacts on living organisms have
      aroused great concern. In this study, the impacts of DMP contamination on
      bacterial communities and functions were tested by using microcosm model in black
      soils. The results showed that the operational taxonomic unit (OTUs) richness and
      bacterial diversity were reduced by DMP contamination. The relative percentages
      of some genera associated with nitrogen metabolism were increased by DMP
      contamination, while the relative percentages of some other genera that were
      extremely beneficial to soil health were decreased by DMP contamination. Further,
      the relative percentages of some genera that possessed the capability to degrade
      DMP were increased by the DMP treatment at low concentrations (5, 10, and 20
      mg/kg), but were decreased by the high concentration DMP treatment (40 mg/kg).
      Clearly, DMP contamination changed the bacterial community structure and
      disturbed the metabolic activity and functional diversity of the microbes in
      black soils. Our results suggest that DMP pollution can alter the metabolism and
      biodiversity of black soil microorganisms, thereby directly impact fertility and
      ecosystem functions. 

PMID- 25999933
TI  - Molecular characterization of a bipartite double-stranded RNA virus and its
      satellite-like RNA co-infecting the phytopathogenic fungus Sclerotinia
      sclerotiorum.
AB  - A variety of mycoviruses have been found in Sclerotinia sclerotiorum. In this
      study, we report a novel mycovirus S. sclerotiorum botybirnavirus 1 (SsBRV1) that
      was originally isolated from the hypovirulent strain SCH941 of S. sclerotiorum.
      SsBRV1 has rigid spherical virions that are ~38 nm in diameter, and three double
      stranded RNA (dsRNA) segments (dsRNA1, 2, and 3 with lengths of 6.4, 6.0, and 1.7
      kbp, respectively) were packaged in the virions. dsRNA1 encodes a cap-pol fusion
      protein, and dsRNA2 encodes a polyprotein with unknown functions but contributes
      to the formation of virus particles. The dsRNA3 is dispensable and may be a
      satellite-like RNA of SsBRV1. Although phylogenetic analysis of the RdRp domain
      demonstrated that SsBRV1 is related to Botrytis porri RNA virus 1 (BpRV1) and
      Ustilago maydis dsRNA virus-H1, the structure proteins of SsBRV1 do not have any
      significant sequence similarities with other known viral proteins with the
      exception of those of BpRV1. SsBRV1 carrying dsRNA3 seems to have no obvious
      effects on the colony morphology, but can significantly reduce the growth rate
      and virulence of S. sclerotiorum. These findings provide new insights into the
      virus taxonomy, virus evolution and the interactions between SsBRV1 and the
      fungal hosts. 

PMID- 25999934
TI  - Data-driven integration of genome-scale regulatory and metabolic network models.
AB  - Microbes are diverse and extremely versatile organisms that play vital roles in
      all ecological niches. Understanding and harnessing microbial systems will be key
      to the sustainability of our planet. One approach to improving our knowledge of
      microbial processes is through data-driven and mechanism-informed computational
      modeling. Individual models of biological networks (such as metabolism,
      transcription, and signaling) have played pivotal roles in driving microbial
      research through the years. These networks, however, are highly interconnected
      and function in concert-a fact that has led to the development of a variety of
      approaches aimed at simulating the integrated functions of two or more network
      types. Though the task of integrating these different models is fraught with new
      challenges, the large amounts of high-throughput data sets being generated, and
      algorithms being developed, means that the time is at hand for concerted efforts
      to build integrated regulatory-metabolic networks in a data-driven fashion. In
      this perspective, we review current approaches for constructing integrated
      regulatory-metabolic models and outline new strategies for future development of
      these network models for any microbial system. 

PMID- 25999935
TI  - Editorial: Role of lipids in virus assembly.

PMID- 25999936
TI  - Paving the way for predictive diagnostics and personalized treatment of invasive
      aspergillosis.
AB  - Invasive aspergillosis (IA) is a life-threatening fungal disease commonly
      diagnosed among individuals with immunological deficits, namely hematological
      patients undergoing chemotherapy or allogeneic hematopoietic stem cell
      transplantation. Vaccines are not available, and despite the improved diagnosis
      and antifungal therapy, the treatment of IA is associated with a poor outcome.
      Importantly, the risk of infection and its clinical outcome vary significantly
      even among patients with similar predisposing clinical factors and
      microbiological exposure. Recent insights into antifungal immunity have further
      highlighted the complexity of host-fungus interactions and the multiple pathogen
      sensing systems activated to control infection. How to decode this information
      into clinical practice remains however, a challenging issue in medical mycology.
      Here, we address recent advances in our understanding of the host-fungus
      interaction and discuss the application of this knowledge in potential strategies
      with the aim of moving toward personalized diagnostics and treatment
      (theranostics) in immunocompromised patients. Ultimately, the integration of
      individual traits into a clinically applicable process to predict the risk and
      progression of disease, and the efficacy of antifungal prophylaxis and therapy,
      holds the promise of a pioneering innovation benefiting patients at risk of IA. 

PMID- 25999937
TI  - Actinobacterial diversity in limestone deposit sites in Hundung, Manipur (India)
      and their antimicrobial activities.
AB  - Studies on actinobacterial diversity in limestone habitats are scarce. This paper
      reports profiling of actinobacteria isolated from Hundung limestone samples in
      Manipur, India using ARDRA as the molecular tool for preliminary classification.
      A total of 137 actinobacteria were clustered into 31 phylotypic groups based on
      the ARDRA pattern generated and representative of each group was subjected to 16S
      rRNA gene sequencing. Generic diversity of the limestone isolates consisted of
      Streptomyces (15 phylotypic groups), Micromonospora (4), Amycolatopsis (3),
      Arthrobacter (3), Kitasatospora (2), Janibacter (1), Nocardia (1), Pseudonocardia
      (1) and Rhodococcus (1). Considering the antimicrobial potential of these
      actinobacteria, 19 showed antimicrobial activities against at least one of the
      bacterial and candidal test pathogens, while 45 exhibit biocontrol activities
      against at least one of the rice fungal pathogens. Out of the 137 actinobacterial
      isolates, 118 were found to have at least one of the three biosynthetic gene
      clusters (PKS-I, PKS-II, NRPS). The results indicate that 86% of the strains
      isolated from Hundung limestone deposit sites possessed biosynthetic gene
      clusters of which 40% exhibited antimicrobial activities. It can, therefore, be
      concluded that limestone habitat is a promising source for search of novel
      secondary metabolites. 

PMID- 25999938
TI  - Ecological prevalence, genetic diversity, and epidemiological aspects of
      Salmonella isolated from tomato agricultural regions of the Virginia Eastern
      Shore.
AB  - Virginia is the third largest producer of fresh-market tomatoes in the United
      States. Tomatoes grown along the eastern shore of Virginia are implicated almost
      yearly in Salmonella illnesses. Traceback implicates contamination occurring in
      the pre-harvest environment. To get a better understanding of the ecological
      niches of Salmonella in the tomato agricultural environment, a 2-year study was
      undertaken at a regional agricultural research farm in Virginia. Environmental
      samples, including tomato (fruit, blossoms, and leaves), irrigation water,
      surface water and sediment, were collected over the growing season. These samples
      were analyzed for the presence of Salmonella using modified FDA-BAM methods.
      Molecular assays were used to screen the samples. Over 1500 samples were tested.
      Seventy-five samples tested positive for Salmonella yielding over 230 isolates.
      The most commonly isolated serovars were S. Newport and S. Javiana with pulsed
      field gel electrophoresis yielding 39 different patterns. Genetic diversity was
      further underscored among many other serotypes, which showed multiple PFGE
      subtypes. Whole genome sequencing (WGS) of several S. Newport isolates collected
      in 2010 compared to clinical isolates associated with tomato consumption showed
      very few single nucleotide differences between environmental isolates and
      clinical isolates suggesting a source link to Salmonella contaminated tomatoes.
      Nearly all isolates collected during two growing seasons of surveillance were
      obtained from surface water and sediment sources pointing to these sites as long
      term reservoirs for persistent and endemic contamination of this environment. 

PMID- 25999940
TI  - Corrigendum: Importance of adhesins in virulence of Paracoccidioides spp.

PMID- 25999939
TI  - Recent advances toward a molecular mechanism of efflux pump inhibition.
AB  - Multidrug resistance (MDR) in Gram-negative pathogens, such as the
      Enterobacteriaceae and Pseudomonas aeruginosa, poses a significant threat to our
      ability to effectively treat infections caused by these organisms. A major
      component in the development of the MDR phenotype in Gram-negative bacteria is
      overexpression of Resistance-Nodulation-Division (RND)-type efflux pumps, which
      actively pump antibacterial agents and biocides from the periplasm to the outside
      of the cell. Consequently, bacterial efflux pumps are an important target for
      developing novel antibacterial treatments. Potent efflux pump inhibitors (EPIs)
      could be used as adjunctive therapies that would increase the potency of existing
      antibiotics and decrease the emergence of MDR bacteria. Several potent inhibitors
      of RND-type efflux pump have been reported in the literature, and at least three
      of these EPI series were optimized in a pre-clinical development program.
      However, none of these compounds have been tested in the clinic. One of the major
      hurdles to the development of EPIs has been the lack of biochemical,
      computational, and structural methods that could be used to guide rational drug
      design. Here, we review recent reports that have advanced our understanding of
      the mechanism of action of several potent EPIs against RND-type pumps. 

PMID- 25999941
TI  - Prevalence and antimicrobial resistance of Shigella flexneri serotype 2 variant
      in China.
AB  - Shigella flexneri serotype 2 variant (II:3,4,7,8) was isolated in 2008 and first
      reported in China in 2013. In the present study, epidemiological surveillance
      from 2003 to 2013 in China suggested that this serotype first appeared in Guangxi
      in 2003; it then emerged in Shanghai and Xinjiang in 2004 and in Henan in 2008.
      Of the 1813 S. flexneri isolates, 58 S. flexneri serotype 2 variant strains were
      identified. Serotype 2 variant has emerged as a prominent serotype in recent
      years, with 2a (32.6%), X variant (25.2%), 1a (9.4%), X (6.3%), 2b (5.4%), and 1b
      (3.6%). According to phenotypic and genotypic analysis, the serotype 2 variant
      originated from 2a to 2b. A higher antibiotic resistance rate was observed
      between 2009 and 2013 than that between 2003 and 2008. Among 22 cephalosporin
      resistant isolates, bla TEM-1, bla OXA-1, bla CTX-3, bla CTX-14, and bla CTX-79
      were detected. Among 22 fluoroquinolone-resistant isolates, a Ser80Ile mutation
      in parC was present in all of the isolates. Moreover, 21 isolates had three gyrA
      point mutations (Ser83Leu, His211Tyr, Asp87Asn, or Gly) and one isolate had two
      gyrA point mutations (Ser83Leu and His211Tyr). The prevalence of His211Tyr in the
      fluoroquinolone-resistant isolates is concerning, and the mutation was first
      reported in China. Besides, 22 isolates harbored the aac(6')-Ib-cr gene, and two
      isolates harbored qnrS1. In view of the increased epidemic frequency and
      multidrug-resistant strain emergence, continuous surveillance will be needed to
      understand the actual disease burden and provide guidance for shigellosis. 

PMID- 25999942
TI  - Identification of DHA-23, a novel plasmid-mediated and inducible AmpC beta
      lactamase from Enterobacteriaceae in Northern Taiwan.
AB  - OBJECTIVES: AmpC beta-lactamases are classified as Amber Class C and Bush Group
      1. AmpC beta-lactamases can hydrolyze broad and extended-spectrum cephalosporins,
      and are not inhibited by beta-lactamase inhibitors such as clavulanic acid. This
      study was conducted to identify DHA-23, a novel plasmid-mediated and inducible
      AmpC beta-lactamase obtained from Enterobacteriaceae. METHODS: A total of 210
      carbapenem-resistant Enterobacteriaceae isolates were collected from a medical
      center (comprising two branches) in Northern Taiwan during 2009-2012. AmpC beta
      lactamase genes were analyzed through a polymerase chain reaction using plasmid
      DNA templates and gene sequencing. The genetic relationships of the isolates were
      typed using pulsed-field gel electrophoresis following the digestion of intact
      genomic DNA by using XbaI. RESULTS: Three enterobacterial isolates (one
      Escherichia coli and two Klebsiella pneumoniae) were obtained from three
      hospitalized patients. All three isolates were resistant or intermediately
      susceptible to all beta-lactams, and exhibited reduced susceptibility to
      carbapenems. These three isolates expressed a novel AmpC beta-lactamase,
      designated DHA-23, approved by the curators of the Lahey website. DHA-23 differs
      from DHA-1 and DHA-6 by one amino acid substitution (Ser245Ala), exhibiting three
      amino acid changes compared with DHA-7 and DHA-Morganella morganii; three amino
      acid changes compared with DHA-3; four amino acid changes compared with DHA-5;
      and eight amino acid changes compared with DHA-2 (>97% identity). This AmpC beta
      lactamase is inducible using a system involving ampR. CONCLUSION: This is the
      first report to address DHA-23, a novel AmpC beta-lactamase. DHA-type beta
      lactamases are continuous threat in Taiwan.

PMID- 25999943
TI  - Common occurrence of antibacterial agents in human intestinal microbiota.
AB  - Laboratory experiments have revealed many active mechanisms by which bacteria can
      inhibit the growth of other organisms. Bacteriocins are a diverse group of
      natural ribosomally synthesized antimicrobial peptides produced by a wide range
      of bacteria and which seem to play an important role in mediating competition
      within bacterial communities. In this study, we have identified and established
      the structural classification of putative bacteriocins encoded by 317 microbial
      genomes in the human intestine. On the basis of homologies to available
      bacteriocin sequences, mainly from lactic acid bacteria, we report the widespread
      occurrence of bacteriocins across the gut microbiota: 175 bacteriocins were found
      to be encoded in Firmicutes, 79 in Proteobacteria, 34 in Bacteroidetes, and 25 in
      Actinobacteria. Bacteriocins from gut bacteria displayed wide differences among
      phyla with regard to class distribution, net positive charge, hydrophobicity and
      secondary structure, but the alpha-helix was the most abundant structure. The
      peptide structures and physiochemical properties of bacteriocins produced by the
      most abundant bacteria in the gut, the Firmicutes and the Bacteroidetes, seem to
      ensure low antibiotic activity and participate in permanent intestinal host
      defense against the proliferation of harmful bacteria. Meanwhile, the potentially
      harmful bacteria, including the Proteobacteria, displayed highly effective
      bacteriocins, probably supporting the virulent character of diseases. These
      findings highlight the eventual role played by bacteriocins in gut microbial
      competition and their potential place in antibiotic therapy. 

PMID- 25999944
TI  - Early-onset autoimmune disease as a manifestation of primary immunodeficiency.
AB  - Autoimmune disorders (AID) have been increasingly observed in association with
      primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and
      AID, focusing on autoimmune manifestations early in life, which can be diagnostic
      clues for underlying PIDs. Inflammatory bowel disease in infants and children has
      been associated with IL-10 and IL-10R deficiencies, chronic granulomatous
      disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome
      (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as
      underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM
      deficiencies, alterations of the IFN-alpha pathway (in Aicardi-Goutieres syndrome
      due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell
      deficiency), usually appearing in the first months of life, was recently observed
      in miscarried fetuses with hydrops who presented with CD3+ infiltrating
      lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin
      deficiency was also identified as a cause of fetal hydrops. In conclusion, PID
      should be suspected in any infant with signs of autoimmunity after excluding
      transferred maternal effects, or in children with multiple and/or severe AID. 

PMID- 25999945
TI  - Fate mapping of dendritic cells.
AB  - Dendritic cells (DCs) are a heterogeneous group of mononuclear phagocytes with
      versatile roles in immunity. They are classified predominantly based on
      phenotypic and functional properties, namely their stellate morphology,
      expression of the integrin CD11c, and major histocompatibility class II
      molecules, as well as their superior capacity to migrate to secondary lymphoid
      organs and stimulate naive T cells. However, these attributes are not exclusive
      to DCs and often change within inflammatory or infectious environments. This led
      to debates over cell identification and questioned even the mere existence of DCs
      as distinct leukocyte lineage. Here, we review experimental approaches taken to
      fate map DCs and discuss how these have shaped our understanding of DC ontogeny
      and lineage affiliation. Considering the ontogenetic properties of DCs will help
      to overcome the inherent shortcomings of purely phenotypic- and function-based
      approaches to cell definition and will yield a more robust way of DC
      classification. 

PMID- 25999948
TI  - Antiphospholipid Antibodies and Antiphospholipid Syndrome during Pregnancy:
      Diagnostic Concepts.
AB  - Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and
      obstetric manifestations linked to the presence of antiphospholipid antibodies
      (aPL). APS was described in the context of lupus, and later as an isolated
      syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant
      test, is associated with adverse pregnancy outcomes, such as fetal death,
      recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but
      does not seem to influence infertility. High quality scientific data to support
      these associations, however, are lacking, and controversies arise about the
      definition of positive aPL (low vs medium-high titers) or even the definition of
      the adverse events. This review discusses APS classification criteria and the
      current debate about it. 

PMID- 25999947
TI  - Emerging roles of exosomes in normal and pathological conditions: new insights
      for diagnosis and therapeutic applications.
AB  - From the time when they were first described in the 1970s by the group of
      Johnstone and Stahl, exosomes are a target of constant research. Exosomes belong
      to the family of nanovesicles which are of great interest for their many
      functions and potential for diagnosis and therapy in multiples diseases. Exosomes
      originate from the intraluminal vesicles of late endosomal compartments named
      multivesicular bodies and the fusion of these late endosomes with the cell
      membrane result in the release of the vesicles into the extracellular
      compartment. Moreover, their generation can be induced by many factors including
      extracellular stimuli, such as microbial attack and other stress conditions. The
      primary role attributed to exosomes was the removal of unnecessary proteins from
      the cells. Now, several studies have demonstrated that exosomes are involved in
      cell-cell communication, even though their biological function is not completely
      clear. The participation of exosomes in cancer is the field of microvesicle
      research that has expanded more over the last years. Evidence proving that
      exosomes derived from tumor-pulsed dendritic cells, neoplastic cells, and
      malignant effusions are able to present antigens to T-cells, has led to numerous
      studies using them as cell-free cancer vaccines. Because exosomes derive from all
      cell types, they contain proteins, lipids, and micro RNA capable of regulating a
      variety of target genes. Much research is being conducted, which focuses on the
      employment of these vesicles as biomarkers in the diagnosis of cancer in addition
      to innovative biomarkers for diagnosis, prognosis, and management of
      cardiovascular diseases. Interesting findings indicating the role of exosomes in
      the pathogenesis of several diseases have encouraged researchers to consider
      their therapeutic potential not only in oncology but also in the treatment of
      autoimmune syndromes and neurodegenerative disorders such as Alzheimer's and
      Parkinson's disease, in addition to infectious diseases such as tuberculosis,
      diphtheria, and toxoplasmosis as well as infections caused by prions or viruses
      such as HIV. The aim of this review is to disclose the emerging roles of exosomes
      in normal and pathological conditions and to discuss their potential therapeutic
      applications. 

PMID- 25999949
TI  - Surface Plasmon Resonance Analysis Shows an IgG-Isotype-Specific Defect in ABO
      Blood Group Antibody Formation in Patients with Common Variable Immunodeficiency.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the most common clinically
      severe primary immunodeficiency and comprises a heterogeneous group of patients
      with recurrent severe bacterial infections due to the failure to produce IgG
      antibodies after exposure to infectious agents and immunization. Diagnostic
      recommendations for antibody failure include assessment of isoagglutinins. We
      have readdressed this four decades old but still accepted recommendation with up
      to date methodology. METHODS: Anti-A/B IgM- and IgG-antibodies were measured by
      Diamed-ID Micro Typing, surface plasmon resonance (SPR) using the Biacore((r))
      device and flow cytometry. RESULTS: When Diamed-ID Micro Typing was used, CVID
      patients (n = 34) showed IgG- and IgM-isoagglutinins that were comparable to
      healthy volunteers (n = 28), while all XLA patients (n = 8) had none. Anti-A/B
      IgM-antibodies were present in more than 2/3 of the CVID patients and showed
      binding kinetics comparable to anti-A/B IgM-antibodies from healthy individuals.
      A correlation could be found in CVID patients between levels of anti-A/B IgM
      antibodies and levels of serum IgM and PnP-IgM-antibodies. In contrast in CVID
      patients as a group ABO antibodies were significantly decreased when assessed by
      SPR, which correlated with levels of switched memory, non-switched memory and
      naive B cells, but all CVID patients had low/undetectable anti-A/B IgG
      antibodies. CONCLUSION: These results indicate that conventional isoagglutinin
      assessment and assessment of anti-A/B IgM antibodies are not suited for the
      diagnosis of impaired antibody production in CVID. Examination of anti-A/B IgG
      antibodies by SPR provides a useful method for the diagnosis of IgG antibody
      failure in all CVID patients studied, thus indicating an important additional
      rationale to start immunoglobulin replacement therapy early in these patients,
      before post-infectious sequelae develop.

PMID- 25999950
TI  - Anatomy of a discovery: m1 and m2 macrophages.
AB  - M1 and M2 macrophage-type responses kill or repair in vivo. The unique ability of
      macrophages to make these polar opposite type of responses provides primary host
      protection and maintains tissue homeostasis throughout the animal kingdom. In
      humans and other higher animals, M1 and M2-type macrophage responses also
      initiate and direct T cells/adaptive immunity to provide additional protection
      such as Th1 (cytotoxic) or Th2 (antibody-mediated) type responses. Hence,
      macrophages were renamed M1 and M2 to indicate the central role of
      macrophages/innate immunity in immune systems. These findings indicate that the
      long held notion that adaptive immunity controls innate immunity was backward: a
      sea change in understanding how immune responses occur. The clinical impact of
      M1/kill and M2/repair responses is immense playing pivotal roles in curing (or
      causing) many diseases including infections, cancer, autoimmunity, and
      atherosclerosis. How M1/M2 came to be is an interesting story that, like life,
      involved Direction, Determination, Discouragement, and Discovery. 

PMID- 25999946
TI  - Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the
      Activities of Inflammation and Cancer.
AB  - The glycosaminoglycan hyaluronan (HA), a major component of extracellular
      matrices, and cell surface receptors of HA have been proposed to have pivotal
      roles in cell proliferation, migration, and invasion, which are necessary for
      inflammation and cancer progression. CD44 and receptor for HA-mediated motility
      (RHAMM) are the two main HA-receptors whose biological functions in human and
      murine inflammations and tumor cells have been investigated comprehensively. HA
      was initially considered to be only an inert component of connective tissues, but
      is now known as a "dynamic" molecule with a constant turnover in many tissues
      through rapid metabolism that involves HA molecules of various sizes: high
      molecular weight HA (HMW HA), low molecular weight HA, and oligosaccharides. The
      intracellular signaling pathways initiated by HA interactions with CD44 and RHAMM
      that lead to inflammatory and tumorigenic responses are complex. Interestingly,
      these molecules have dual functions in inflammations and tumorigenesis. For
      example, the presence of CD44 is involved in initiation of arthritis, while the
      absence of CD44 by genetic deletion in an arthritis mouse model increases rather
      than decreases disease severity. Similar dual functions of CD44 exist in
      initiation and progression of cancer. RHAMM overexpression is most commonly
      linked to cancer progression, whereas loss of RHAMM is associated with malignant
      peripheral nerve sheath tumor growth. HA may similarly perform dual functions. An
      abundance of HMW HA can promote malignant cell proliferation and development of
      cancer, whereas antagonists to HA-CD44 signaling inhibit tumor cell growth in
      vitro and in vivo by interfering with HMW HA-CD44 interaction. This review
      describes the roles of HA interactions with CD44 and RHAMM in inflammatory
      responses and tumor development/progression, and how therapeutic strategies that
      block these key inflammatory/tumorigenic processes may be developed in rodent and
      human diseases. 

PMID- 25999951
TI  - Of monkeys and men: immunomic profiling of sera from humans and non-human
      primates resistant to schistosomiasis reveals novel potential vaccine candidates.
AB  - Schistosoma haematobium affects more than 100 million people throughout Africa
      and is the causative agent of urogenital schistosomiasis. The parasite is
      strongly associated with urothelial cancer in infected individuals and as such is
      designated a group I carcinogen by the International Agency for Research on
      Cancer. Using a protein microarray containing schistosome proteins, we sought to
      identify antigens that were the targets of protective IgG1 immune responses in S.
      haematobium-exposed individuals that acquire drug-induced resistance (DIR) to
      schistosomiasis after praziquantel treatment. Numerous antigens with known
      vaccine potential were identified, including calpain (Smp80), tetraspanins,
      glutathione-S-transferases, and glucose transporters (SGTP1), as well as
      previously uncharacterized proteins. Reactive IgG1 responses were not elevated in
      exposed individuals who did not acquire DIR. To complement our human subjects
      study, we screened for antigen targets of rhesus macaques rendered resistant to
      S. japonicum by experimental infection followed by self-cure, and discovered a
      number of new and known vaccine targets, including major targets recognized by
      our human subjects. This study has further validated the immunomics-based
      approach to schistosomiasis vaccine antigen discovery and identified numerous
      novel potential vaccine antigens. 

PMID- 25999955
TI  - A Commentary On: "NFkappaB-Activated Astroglial Release of Complement C3
      Compromises Neuronal Morphology and Function Associated with Alzheimer's
      Disease". A cautionary note regarding C3aR.

PMID- 25999952
TI  - Chemokine function in periodontal disease and oral cavity cancer.
AB  - The chemotactic cytokines, or chemokines, comprise a superfamily of polypeptides
      with a wide range of activities that include recruitment of immune cells to sites
      of infection and inflammation, as well as stimulation of cell proliferation. As
      such, they function as antimicrobial molecules and play a central role in host
      defenses against pathogen challenge. However, their ability to recruit leukocytes
      and potentiate or prolong the inflammatory response may have profound
      implications for the progression of oral diseases such as chronic periodontitis,
      where tissue destruction may be widespread. Moreover, it is increasingly
      recognized that chronic inflammation is a key component of tumor progression.
      Interaction between cancer cells and their microenvironment is mediated in large
      part by secreted factors such as chemokines, and serves to enhance the malignant
      phenotype in oral and other cancers. In this article, we will outline the
      biological and biochemical mechanisms of chemokine action in host-microbiome
      interactions in periodontal disease and in oral cancer, and how these may overlap
      and contribute to pathogenesis. 

PMID- 25999953
TI  - Complement-Coagulation Cross-Talk: A Potential Mediator of the Physiological
      Activation of Complement by Low pH.
AB  - The complement system is a major constituent of the innate immune system. It not
      only bridges innate and adaptive arms of the immune system but also links the
      immune system with the coagulation system. Current understanding of the role of
      complement has extended far beyond fighting of infections, and now encompasses
      maintenance of homeostasis, tissue regeneration, and pathophysiology of multiple
      diseases. It has been known for many years that complement activation is strongly
      pH sensitive, but only relatively recently has the physiological significance of
      this been appreciated. Most complement assays are carried out at the
      physiological pH 7.4. However, pH in some extracellular compartments, for
      example, renal tubular fluid in parts of the tubule, and extracellular fluid at
      inflammation loci, is sufficiently acidic to activate complement. The exact
      molecular mechanism of this activation is still unclear, but possible cross-talk
      between the contact system (intrinsic pathway) and complement may exist at low pH
      with subsequent complement activation. The current article reviews the published
      data on the effect of pH on the contact system and complement activity, the
      nature of the pH sensor molecules, and the clinical implications of these
      effects. Of particular interest is chronic kidney disease (CKD) accompanied by
      metabolic acidosis, in which therapeutic alkalinization of urine has been shown
      significantly to reduce tubular complement activation products, an effect, which
      may have important implications for slowing progression of CKD. 

PMID- 25999954
TI  - Shigella manipulates host immune responses by delivering effector proteins with
      specific roles.
AB  - The intestinal epithelium deploys multiple defense systems against microbial
      infection to sense bacterial components and danger alarms, as well as to induce
      intracellular signal transduction cascades that trigger both the innate and the
      adaptive immune systems, which are pivotal for bacterial elimination. However,
      many enteric bacterial pathogens, including Shigella, deliver a subset of
      virulence proteins (effectors) via the type III secretion system (T3SS) that
      enable bacterial evasion from host immune systems; consequently, these pathogens
      are able to efficiently colonize the intestinal epithelium. In this review, we
      present and select recently discovered examples of interactions between Shigella
      and host immune responses, with particular emphasis on strategies that bacteria
      use to manipulate inflammatory outputs of host-cell responses such as cell death,
      membrane trafficking, and innate and adaptive immune responses. 

PMID- 25999956
TI  - Hyperphosphate-Induced Myocardial Hypertrophy through the GATA-4/NFAT-3 Signaling
      Pathway Is Attenuated by ERK Inhibitor Treatment.
AB  - BACKGROUND/AIMS: Numerous epidemiological studies have associated elevated serum
      phosphorus levels with cardiovascular disease and the risk of death in the
      general population as well as in chronic kidney disease (CKD) and dialysis
      patients. In this study, we explored whether elevated phosphate conditions induce
      cardiac hypertrophy and attempted to identify the molecular and cellular
      mechanisms in the hypertrophic response. METHODS: H9c2 myocardial cells were
      incubated in high-phosphate conditions to induce hypertrophy. Pathological
      hypertrophic responses were measured in terms of cell size, arrangement of actin
      filaments, and hypertrophy markers such as atrial natriuretic peptide (ANP) and B
      type natriuretic peptide (BNP) in myocardial cells. Several transcriptional
      factors involved in cardiac hypertrophy development were measured to investigate
      the molecular pathways involved in elevated phosphate-induced cardiac
      hypertrophy. RESULTS: High-phosphate conditions induced cellular hypertrophy,
      marked by increased cell size, reorganization of actin filaments, and
      upregulation of both ANP and BNP in H9c2 cells. Both upstream calcineurin and
      downstream transcription factors, including GATA-4 and NFAT-3, were significantly
      increased under hyperphosphate conditions. Moreover, both MEK1/2 and ERK1/2
      expression increased significantly, and cellular hypertrophy was markedly
      attenuated by U0126, an ERK1/2 inhibitor. CONCLUSIONS: These results suggest that
      hyperphosphate conditions induce myocardial hypertrophy through the ERK signaling
      pathway in H9c2 cells. Our findings provide a link between the hyperphosphate
      induced response and the ERK/NFAT-3 signaling pathway that mediates the
      development of cardiac hypertrophy. In view of the potent and selective activity
      of the ERK inhibitor U0126, this agent warrants further investigation as a
      candidate for preventing hyperphosphate-induced cardiac hypertrophy in CKD and
      dialysis patients.

PMID- 25999957
TI  - High levels of soluble tumor necrosis factor receptors 1 and 2 and their
      association with mortality in patients undergoing hemodialysis.
AB  - OBJECTIVE: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1
      and sTNFR2) are associated with chronic kidney disease (CKD) progression in
      patients with CKD or diabetes, and with higher mortality. However, data in
      patients with end-stage renal disease are scarce. Therefore, we analyzed serum
      levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory
      markers and mortality in dialysis patients. RESEARCH DESIGN AND METHODS: This was
      a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56%
      men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical
      characteristics, including comorbidities and laboratory data, were obtained at
      baseline, together with prospective follow-up for mortality. RESULTS: The median
      sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023
      18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up
      of 31 months (interquartile range, 21-38), 77 patients died. There was no
      association between the levels of sTNFRs and mortality in Cox regression models,
      and no consistent trend towards higher or lower mortality was seen in Laplace
      regression models. sTNFR1 and sTNFR2 levels were highly associated with other
      inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha.
      CONCLUSIONS: Prevalent hemodialysis patients have several-fold higher levels of
      sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent
      association between TNFR and mortality was observed, clinical implications of
      measuring these receptors to predict outcome end-stage renal disease patients
      provide limited results.

PMID- 25999958
TI  - Association between Platelet-to-Lymphocyte Ratio and Contrast-Induced Nephropathy
      in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary
      Syndrome.
AB  - OBJECTIVE: Contrast-induced nephropathy (CIN) is associated with significantly
      increased morbidity and mortality after percutaneous coronary intervention (PCI).
      Patients with acute coronary syndrome (ACS) are at higher risk of CIN. The
      platelet-to-lymphocyte ratio (PLR) is closely linked to inflammatory conditions.
      We hypothesized that PLR levels on admission can predict the development of CIN
      after PCI for ACS. SUBJECTS AND METHODS: A total of 426 patients (mean age 63.17
      +/- 13.01 years, 61.2% males) with ACS undergoing PCI were enrolled in this
      study. Admission PLR levels were measured before PCI. Serum creatinine values
      were measured before and within 72 h after the administration of contrast agents.
      Patients were divided into 2 groups: the CIN group and the no-CIN group. CIN was
      defined as an increase in serum creatinine level of >=0.5 mg/dl or 25% above
      baseline within 72 h after contrast administration. RESULTS: CIN developed in 53
      patients (15.9%). Baseline PLR was significantly higher in patients who developed
      CIN compared to those who did not (160.8 +/- 29.7 and 135.1 +/- 26.1,
      respectively; p < 0.001). Multivariate analyses found that PLR [odds ratio (OR)
      3.453, 95% confidence interval (CI) 1.453-8.543; p = 0.004] and admission
      creatinine (OR 6.511, 95% CI 1.759-11.095; p = 0.002) were independent predictors
      of CIN. CONCLUSIONS: The admission PLR level is an independent predictor of the
      development of CIN after PCI in ACS.

PMID- 25999959
TI  - Cardiorenal syndrome type 1: a defective regulation of monocyte apoptosis induced
      by proinflammatory and proapoptotic factors.
AB  - In this study, we examined the possible immune-mediated mechanisms in cardiorenal
      syndrome (CRS) type 1 pathogenesis. We enrolled 40 patients with acute heart
      failure (AHF), 11 patients with CRS type 1 and 15 controls. Plasma from the
      different groups was incubated with monocytes; subsequently, cell apoptosis was
      evaluated by DNA fragmentation, caspase activity and cytofluorometric assay.
      Cytokine quantification in plasma and supernatant was performed by ELISA.
      Monocytes treated with CRS type 1 plasma showed significantly higher apoptosis
      compared with those treated with AHF and the controls (p < 0.05). Caspase-3 (CRS
      type 1: 2.20 ng/ml, IQR 2.06-2.33; AHF: 1.48 ng/ml, IQR 1.31-1.56; controls: 0.71
      ng/ml, IQR 0.67-0.81) and caspase-8 levels (CRS type 1: 1.49 ng/ml, IQR 1.42
      1.57; AHF: 0.94 ng/ml, IQR 0.84-0.98; controls: 0.56 ng/ml, IQR 0.51-0.58) in
      cells incubated with plasma from these patients demonstrated a significantly
      higher concentration. We observed a strong upregulation of plasma IL-6 and IL-18
      in CRS type 1 compared with AHF and the controls (p < 0.05). Interestingly, we
      observed a similar concentration of TNF-alpha in CRS type 1 and AHF. In CRS type
      1 patients, IL-6 (52.13 ng/ml, IQR 47.29-66.83) and IL-18 levels (197.75 ng/ml,
      IQR 120.80-265.49) in supernatant were significantly higher than in AHF patients
      (IL-6: 28.79 ng/ml, IQR 19.90-36.10; IL-18: 21.98 ng/ml, IQR 15.98-29.85) and
      controls (IL-6: 5.02 ng/ml, IQR 4.56-6.44; IL-18: 7.91 ng/ml, IQR 5.57-10.62).
      These findings suggest the presence of a defective regulation of monocyte
      apoptosis in CRS type 1 patients and the involvement of an immune-mediated
      mechanism in the pathophysiology of this syndrome. 

PMID- 25999960
TI  - Effect of Contrast-Induced Nephropathy on the Long-Term Outcome of Patients with
      Non-ST Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) has been traditionally associated
      with increased mortality and adverse cardiovascular events. We sought to
      determine whether CIN has a negative impact on the long-term outcome of patients
      with non-ST segment elevation myocardial infarction (NSTEMI). METHODS: A total of
      312 consecutive patients (mean age 59 years, 76% male) who presented with NSTEMI
      and had undergone an early invasive procedure were retrospectively included. CIN
      was defined as either a 25% or 0.5-mg/dl increase in baseline serum creatinine
      (Cr) 72 h after the procedure. The primary endpoint of the study was mortality in
      the long-term follow-up (38 months, interquartile range 30-40). The secondary
      endpoint consisted of mortality and myocardial infarction (MI). RESULTS: CIN
      developed in 30 (9.6%) patients. Independent predictors of CIN were the contrast
      volume-to-Cr clearance ratio, left ventricular ejection fraction and hemoglobin
      concentration. The primary (20 vs. 8.5%, p = 0.042) and secondary endpoints (33.3
      vs. 17%, p = 0.029) were observed more frequently in patients with CIN during
      long-term follow-up. The unadjusted odds ratio (OR) of CIN was 2.55 [95%
      confidence intervals (CI) 1.04-6.24, p = 0.040] for mortality and 2.15 (CI 1.09
      4.25, p = 0.028) for mortality/MI. However, after adjustment for confounding
      factors, CIN was not an independent predictor of either mortality (OR 1.62, CI
      0.21-12.57, p = 0.646) or mortality/MI (OR 1.12, CI 0.31-4.0, p = 0.860).
      CONCLUSION: The effect of CIN on the long-term outcome of patients with NSTEMI
      was substantially influenced by confounding factors. CIN was a marker, rather
      than a mediator, of increased cardiovascular risk, and the baseline renal
      function was more conclusive as a long-term prognosticator.

PMID- 25999961
TI  - Direct evidence of podocyte damage in cardiorenal syndrome type 2: preliminary
      evidence.
AB  - BACKGROUND: Renal structural alterations have been partially uncovered in
      cardiorenal syndrome (CRS). Patients with CRS may have evidence of tubular
      damage, but markers of glomerular damage other than proteinuria have not been
      thoroughly investigated. The nature of renal damage in CRS may have therapeutic
      implications, as glomerular damage requires tight blood pressure control and
      renin-angiotensin-aldosterone system (RAAS) inhibition. The present investigation
      evaluates patients with CRS type 2 (CRS-2) for direct evidence of glomerular
      damage as evidenced by the presence of urinary podocin. METHODS: The presence of
      glomerular damage was assessed in acutely decompensated patients with CRS-2 and
      healthy controls. Urinary podocin was determined by quantification of a tryptic
      peptide of podocin with high-performance liquid chromatography coupled to tandem
      mass spectrometry (LC-MS/MS). Morning urine samples were collected for podocin,
      creatinine (Cr), and protein. Urinary podocin was expressed in femtomoles of
      podocin/milligram of Cr. RESULTS: The urinary podocin/Cr ratio was greater in
      patients than in controls (0.37 +/- 0.77 vs. 0.06 +/- 0.05 fmol podocin/mg Cr, p
      = 0.04). A total of 40% of the patients had a urinary podocin/Cr ratio greater
      than the upper limit of normal (>0.2 fmol podocin/mg Cr). Patients with an
      elevated podocin/Cr ratio were more likely to have received <=50% of the maximum
      dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      (p = 0.04) than patients with a podocin/Cr ratio in the normal range.
      CONCLUSIONS: CRS-2 may be associated with glomerular damage as evidenced by an
      elevated urinary podocin/Cr ratio. Modulators of RAAS may have a protective
      effect on urinary podocin loss.

PMID- 25999962
TI  - Alteration of cardiovascular structure and function in patients undergoing
      peritoneal dialysis.
AB  - AIMS: Cardiovascular alterations contribute to a high mortality rate in patients
      with end-stage renal disease (ESRD). The aims of the present study are to
      evaluate left ventricular (LV) function and common carotid artery (CCA)
      parameters and to determine risk factors associated with these changes in
      patients undergoing peritoneal dialysis (PD). METHODS: This longitudinal
      prospective study was conducted in 50 ESRD patients in whom PD had been initiated
      and who were observed for 18 months after the commencement of dialysis treatment,
      with echocardiography and CCA ultrasound parameter evaluation. RESULTS: LV
      hypertrophy was observed in 78% of patients at baseline and in 60% after 18
      months of PD treatment. LV systolic and diastolic function was found to be
      significantly better after 18 months of PD treatment. Examining predictors of LV
      systolic function, it was found that total cholesterol was an independent
      positive predictor and endothelin-1 (ET-1) an independent negative predictor of
      LV systolic function after 18 months of treatment with PD (p < 0.001).
      Independent negative predictors of diastolic LV function were hemoglobin and type
      2 diabetes mellitus, and daily collection of urine was an independent positive
      predictor (p < 0.001). Female gender was an independent negative predictor of CCA
      intima-media thickness, whereas body mass index, ET-1 and C-reactive protein were
      independent positive predictors (p < 0.001). CONCLUSIONS: The results suggest
      several novel modifiable mechanisms related to the short-term effects of dialysis
      that are potentially implicated in the development of uremic cardiomyopathy.

PMID- 25999963
TI  - Peritoneal dialysis in patients with refractory congestive heart failure: a
      systematic review.
AB  - BACKGROUND: Refractory congestive heart failure (RCHF) is associated with a high
      mortality rate and is a major contributor to hospital admissions. Peritoneal
      dialysis (PD) is an option to control volume overload and perhaps improve
      outcomes in this challenging patient population. The aim of this systematic
      review is to describe the relative risk-benefit ratio based on data reported
      regarding the use of PD in RCHF. This study was conducted in accordance with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. An
      electronic search of PubMed, Embase, and the Cochrane Library was performed to
      identify relevant studies published from January 1951 to February 2014. Eligible
      studies selected were prospective or retrospective adult population studies on PD
      in the setting of RCHF. The following clinical outcomes were used to assess PD
      therapy: (1) hospitalization rates; (2) heart function; (3) renal function; (4)
      fluid overload, and (5) adverse clinical outcomes. SUMMARY: Of 864 citations, we
      excluded 843 citations and included 21 studies (n = 673 patients). After PD,
      hospitalization days declined significantly (p = 0.0001), and heart function
      improved significantly (left ventricular ejection fraction: p = 0.0013; New York
      Heart Association classification: p = 0.0000). There were no statistically
      significant differences in glomerular filtration rate after PD treatment in non
      chronic kidney disease stage 5D patients (p = 0.1065). Among patients treated
      with PD, body weight decreased significantly (p = 0.0006). The yearly average
      peritonitis rate was 14.5%, and the average yearly mortality was 20.3%. KEY
      MESSAGES: This systematic review suggests that PD may be an effective and safe
      therapeutic tool for patients with RCHF.

PMID- 25999965
TI  - LSD1 and HY5 antagonistically regulate red light induced-programmed cell death in
      Arabidopsis.
AB  - Programmed cell death (PCD) in plant is triggered by abiotic and biotic stress.
      Light-dependent PCD is unique to plants. Light-induced PCD also requires reactive
      oxygen species (ROS) and salicylic acid (SA). In this study, lesion simulating
      disease1 (LSD1) and elongated hypocotyl 5 (HY5) perform opposite roles to
      regulate excess red light (RL)-triggered PCD associated with ROS and SA
      production. Under RL, the lsd1 mutant released more ROS and SA and displayed a
      stronger cell death rate than the hy5 mutant. It was shown that active LSD1
      converted into inactive form by changing the redox status of the plastoquinone
      pool, and HY5 interacted with phytochrome B (phyB) to promote PCD in response to
      RL. LSD1 inhibited the enhanced disease susceptibility 1 (EDS1) expression by
      upregulating SR1, whereas HY5 enhanced the enhanced EDS1 expression by binding to
      the G-box of the EDS1 promoter. This study suggested that LSD1 and HY5
      antagonistically modulated EDS1-dependent ROS and SA signaling; thus, PCD was
      mediated in response to RL. 

PMID- 25999966
TI  - Resource use and efficiency, and stomatal responses to environmental drivers of
      oak and pine species in an Atlantic Coastal Plain forest.
AB  - Pine-oak ecosystems are globally distributed even though differences in anatomy
      and leaf habit between many co-occurring oaks and pines suggest different
      strategies for resource use, efficiency and stomatal behavior. The New Jersey
      Pinelands contain sandy soils with low water- and nutrient-holding capacity
      providing an opportunity to examine trade-offs in resource uptake and efficiency.
      Therefore, we compared resource use in terms of transpiration rates and leaf
      nitrogen content and resource-use efficiency including water-use efficiency (WUE)
      via gas exchange and leaf carbon isotopes and photosynthetic nitrogen-use
      efficiency (PNUE) between oaks (Quercus alba, Q. prinus, Q. velutina) and pines
      (Pinus rigida, P. echinata). We also determined environmental drivers [vapor
      pressure deficit (VPD), soil moisture, solar radiation] of canopy stomatal
      conductance (GS) estimated via sap flow and stomatal sensitivity to light and
      soil moisture. Net assimilation rates were similar between genera, but oak leaves
      used about 10% more water and pine foliage contained about 20% more N per unit
      leaf area. Therefore, oaks exhibited greater PNUE while pines had higher WUE
      based on gas exchange, although WUE from carbon isotopes was not significantly
      different. For the environmental drivers of GS, oaks had about 10% lower stomatal
      sensitivity to VPD normalized by reference stomatal conductance compared with
      pines. Pines exhibited a significant positive relationship between shallow soil
      moisture and GS, but only GS in Q. velutina was positively related to soil
      moisture. In contrast, stomatal sensitivity to VPD was significantly related to
      solar radiation in all oak species but only pines at one site. Therefore, oaks
      rely more heavily on groundwater resources but have lower WUE, while pines have
      larger leaf areas and nitrogen acquisition but lower PNUE demonstrating a trade
      off between using water and nitrogen efficiently in a resource-limited ecosystem.

PMID- 25999964
TI  - NAC-MYB-based transcriptional regulation of secondary cell wall biosynthesis in
      land plants.
AB  - Plant cells biosynthesize primary cell walls (PCW) in all cells and produce
      secondary cell walls (SCWs) in specific cell types that conduct water and/or
      provide mechanical support, such as xylem vessels and fibers. The characteristic
      mechanical stiffness, chemical recalcitrance, and hydrophobic nature of SCWs
      result from the organization of SCW-specific biopolymers, i.e., highly ordered
      cellulose, hemicellulose, and lignin. Synthesis of these SCW-specific biopolymers
      requires SCW-specific enzymes that are regulated by SCW-specific transcription
      factors. In this review, we summarize our current knowledge of the
      transcriptional regulation of SCW formation in plant cells. Advances in research
      on SCW biosynthesis during the past decade have expanded our understanding of the
      transcriptional regulation of SCW formation, particularly the functions of the
      NAC and MYB transcription factors. Focusing on the NAC-MYB-based transcriptional
      network, we discuss the regulatory systems that evolved in land plants to modify
      the cell wall to serve as a key component of structures that conduct water and
      provide mechanical support. 

PMID- 25999967
TI  - Phosphoproteomic analysis of the response of maize leaves to drought, heat and
      their combination stress.
AB  - Drought and heat stress, especially their combination, greatly affect crop
      production. Many studies have described transcriptome, proteome and
      phosphoproteome changes in response of plants to drought or heat stress. However,
      the study about the phosphoproteomic changes in response of crops to the
      combination stress is scare. To understand the mechanism of maize responses to
      the drought and heat combination stress, phosphoproteomic analysis was performed
      on maize leaves by using multiplex iTRAQ-based quantitative proteomic and LC
      MS/MS methods. Five-leaf-stage maize was subjected to drought, heat or their
      combination, and the leaves were collected. Globally, heat, drought and the
      combined stress significantly changed the phosphorylation levels of 172, 149, and
      144 phosphopeptides, respectively. These phosphopeptides corresponded to 282
      proteins. Among them, 23 only responded to the combined stress and could not be
      predicted from their responses to single stressors; 30 and 75 only responded to
      drought and heat, respectively. Notably, 19 proteins were phosphorylated on
      different sites in response to the single and combination stresses. Of the seven
      significantly enriched phosphorylation motifs identified, two were common for all
      stresses, two were common for heat and the combined stress, and one was specific
      to the combined stress. The signaling pathways in which the phosphoproteins were
      involved clearly differed among the three stresses. Functional characterization
      of the phosphoproteins and the pathways identified here could lead to new targets
      for the enhancement of crop stress tolerance, which will be particularly
      important in the face of climate change and the increasing prevalence of abiotic
      stressors. 

PMID- 25999968
TI  - Beyond the Western front: targeted proteomics and organelle abundance profiling.
AB  - The application of westerns or immunoblotting techniques for assessing the
      composition, dynamics, and purity of protein extracts from plant material has
      become common practice. While the approach is reproducible, can be readily
      applied and is generally considered robust, the field of plant science suffers
      from a lack of antibody variety against plant proteins. The development of
      approaches that employ mass spectrometry to enable both relative and absolute
      quantification of many hundreds of proteins in a single sample from a single
      analysis provides a mechanism to overcome the expensive impediment in having to
      develop antibodies in plant science. We consider it an opportune moment to
      consider and better develop the adoption of multiple reaction monitoring (MRM)
      based analyses in plant biochemistry. 

PMID- 25999969
TI  - Cyclic nucleotide gated channel gene family in tomato: genome-wide identification
      and functional analyses in disease resistance.
AB  - The cyclic nucleotide gated channel (CNGC) is suggested to be one of the
      important calcium conducting channels. Nevertheless, genome-wide identification
      and systemic functional analysis of CNGC gene family in crop plant species have
      not yet been conducted. In this study, we performed genome-wide identification of
      CNGC gene family in the economically important crop tomato (Solanum lycopersicum
      L.) and analyzed function of the group IVb SlCNGC genes in disease resistance.
      Eighteen CNGC genes were identified in tomato genome, and four CNGC loci that
      were misannotated at database were corrected by cloning and sequencing. Detailed
      bioinformatics analyses on gene structure, domain composition and phylogenetic
      relationship of the SlCNGC gene family were conducted and the group-specific
      feature was revealed. Comprehensive expression analyses demonstrated that SlCNGC
      genes were highly, widely but differently responsive to diverse stimuli.
      Pharmacological assays showed that the putative CNGC activators cGMP and cAMP
      enhanced resistance against Sclerotinia sclerotiorum. Silencing of group IVb
      SlCNGC genes significantly enhanced resistance to fungal pathogens Pythium
      aphanidermatum and S. sclerotiorum, strongly reduced resistance to viral pathogen
      Tobacco rattle virus, while attenuated PAMP- and DAMP-triggered immunity as shown
      by obvious decrease of the flg22- and AtPep1-elicited hydrogen peroxide
      accumulation in SlCNGC-silenced plants. Additionally, silencing of these SlCNGC
      genes significantly altered expression of a set of Ca(2+) signaling genes
      including SlCaMs, SlCDPKs, and SlCAMTA3. Collectively, our results reveal that
      group IV SlCNGC genes regulate a wide range of resistance in tomato probably by
      affecting Ca(2+) signaling. 

PMID- 25999970
TI  - Decision tools for bacterial blight resistance gene deployment in rice-based
      agricultural ecosystems.
AB  - Attempting to achieve long-lasting and stable resistance using uniformly deployed
      rice varieties is not a sustainable approach. The real situation appears to be
      much more complex and dynamic, one in which pathogens quickly adapt to resistant
      varieties. To prevent disease epidemics, deployment should be customized and this
      decision will require interdisciplinary actions. This perspective article aims to
      highlight the current progress on disease resistance deployment to control
      bacterial blight in rice. Although the model system rice-Xanthomonas oryzae pv.
      oryzae has distinctive features that underpin the need for a case-by-case
      analysis, strategies to integrate those elements into a unique decision tool
      could be easily extended to other crops. 

PMID- 25999972
TI  - Minimal evidence for consistent changes in maize DNA methylation patterns
      following environmental stress.
AB  - DNA methylation is a chromatin modification that is sometimes associated with
      epigenetic regulation of gene expression. As DNA methylation can be reversible at
      some loci, it is possible that methylation patterns may change within an organism
      that is subjected to environmental stress. In order to assess the effects of
      abiotic stress on DNA methylation patterns in maize (Zea mays), seeding plants
      were subjected to heat, cold, and UV stress treatments. Tissue was later
      collected from individual adult plants that had been subjected to stress or
      control treatments and used to perform DNA methylation profiling to determine
      whether there were consistent changes in DNA methylation triggered by specific
      stress treatments. DNA methylation profiling was performed by immunoprecipitation
      of methylated DNA followed by microarray hybridization to allow for quantitative
      estimates of DNA methylation abundance throughout the low-copy portion of the
      maize genome. By comparing the DNA methylation profiles of each individual plant
      to the average of the control plants it was possible to identify regions of the
      genome with variable DNA methylation. However, we did not find evidence of
      consistent DNA methylation changes resulting from the stress treatments used in
      this study. Instead, the data suggest that there is a low-rate of stochastic
      variation that is present in both control and stressed plants. 

PMID- 25999971
TI  - Information flow and protein dynamics: the interplay between nuclear magnetic
      resonance spectroscopy and molecular dynamics simulations.
AB  - Proteins participate in information pathways in cells, both as links in the chain
      of signals, and as the ultimate effectors. Upon ligand binding, proteins undergo
      conformation and motion changes, which can be sensed by the following link in the
      chain of information. Nuclear magnetic resonance (NMR) spectroscopy and molecular
      dynamics (MD) simulations represent powerful tools for examining the time
      dependent function of biological molecules. The recent advances in NMR and the
      availability of faster computers have opened the door to more detailed analyses
      of structure, dynamics, and interactions. Here we briefly describe the recent
      applications that allow NMR spectroscopy and MD simulations to offer unique
      insight into the basic motions that underlie information transfer within and
      between cells. 

PMID- 25999973
TI  - Elevation-dependent variations of tree growth and intrinsic water-use efficiency
      in Schrenk spruce (Picea schrenkiana) in the western Tianshan Mountains, China.
AB  - Rising atmospheric CO2 concentration (C a) is expected to accelerate tree growth
      by enhancing photosynthesis and increasing intrinsic water-use efficiency (iWUE).
      However, the extent of this effect on long-term iWUE and its interactions with
      climate remains unclear in trees along an elevation gradient. Therefore, we
      investigated the variation in the radial growth and iWUE of mature Picea
      schrenkiana trees located in the upper tree-line (A1: 2700 m a.s.l.), middle
      elevation (A2: 2400 m a.s.l.), and lower forest limit (A3: 2200 m a.s.l.), in
      relation to the rising C a and changing climate in the Wusun Mountains of
      northwestern China, based on the basal area increment (BAI) and tree-ring
      delta(13)C chronologies from 1960 to 2010. We used the CRU TS3.22 dataset to
      analyze the general response of tree growth to interannual variability of
      regional climate, and found that BAI and delta(13)C are less sensitive to climate
      at A1 than at A2 and A3. The temporal trends of iWUE were calculated under three
      theoretical scenarios, as a baseline for interpreting the observed gas exchange
      at increasing C a. We found that iWUE increased by 12-32% from A1 to A3 over the
      last 50 years, and showed an elevation-dependent variation in physiological
      response. The significant negative relationship between BAI and iWUE at A2 and A3
      showed that tree growth has been decreasing despite long-term increases in iWUE.
      However, BAI remained largely stable throughout the study period despite the
      strongest iWUE increase [at constant intercellular CO2 concentration (C i) before
      1980] at A1. Our results indicate a drought-induced limitation of tree growth
      response to rising CO2 at lower elevations, and no apparent change in tree growth
      and diminished iWUE improvement since 1980 in the upper tree-line. This study may
      contradict the expectation that combined effects of elevated C a and rising
      temperatures have increased forest productivity, especially in high-elevation
      forests. 

PMID- 25999974
TI  - Targeting proteins for proteasomal degradation-a new function of Arabidopsis ABI1
      protein phosphatase 2C.
AB  - The ubiquitin/26S proteasome system (UPS) has been implicated in the regulation
      of many physiological processes including hormone signaling. The plant hormone
      abscisic acid (ABA) employs the UPS to control its own synthesis and signaling
      and to regulate stress response and tolerance. Among the known effectors of ABA
      signaling, the ABI1 (abscisic acid-insensitive 1) protein phosphatase, which
      belongs to group A of the type 2C protein phosphatases, is recognized as a key
      component of the pathway. Molecular and genetic evidence implicates this protein
      phosphatase in numerous plant responses. This mini-review discusses recent
      progress in understanding the role of ABI1 in ABA signaling, with particular
      emphasis on recent data that link ABI1 to protein degradation via the UPS. 

PMID- 25999976
TI  - FocVel1 influences asexual production, filamentous growth, biofilm formation, and
      virulence in Fusarium oxysporum f. sp. cucumerinum.
AB  - Velvet genes play critical roles in the regulation of diverse cellular processes.
      In current study, we identified the gene FocVel1, a homolog of Fusarium
      graminearum VelA, in the plant pathogenic fungus F. oxysporum f. sp. cucumerinum.
      This pathogen causes the destructive disease called cucumber Fusarium wilt (CFW),
      which severely affects the production and marketing of this vegetable worldwide.
      Transcript analyses revealed high expression of FocVel1 during conidiophore
      development. Disruption of the FocVel1 gene led to several phenotypic defects,
      including reduction in aerial hyphal formation and conidial production. The
      deletion mutant DeltaFocVel1 showed increased resistance to both osmotic stress
      and cell wall-damaging agents, but increased sensitivity to iprodione and
      prochloraz fungicides, which may be related to changes in cell wall components.
      In the process of biofilm formation in vitro, the mutant strain DeltaFocVel1
      displayed not only a reduction in spore aggregation but also a delay in conidial
      germination on the polystyrene surface, which may result in defects in biofilm
      formation. Moreover, pathogenicity assays showed that the mutant DeltaFocVel1
      exhibited impaired virulence in cucumber seedlings. And the genetic
      complementation of the mutant with the wild-type FocVel1 gene restored all the
      defects of the DeltaFocVel1. Taken together, the results of this study indicated
      that FocVel1 played a critical role in the regulation of various cellular
      processes and pathogenicity in F. oxysporum f. sp. cucumerinum. 

PMID- 25999977
TI  - A molecular method to identify species of fine roots and to predict the
      proportion of a species in mixed samples in subtropical forests.
AB  - Understanding of belowground interactions among tree species and the fine root
      (<=2 mm in diameter) contribution of a species to forest ecosystem production are
      mostly restricted by experimental difficulties in the quantification of the
      species composition. The available approaches have various defects. By contrast,
      DNA-based methods can avoid these drawbacks. Quantitative real-time polymerase
      chain reaction (PCR) is an advanced molecular technology, but it is difficult to
      develop specific primer sets. The method of next-generation sequencing has
      several limitations, such as inaccurate sequencing of homopolymer regions, as
      well as being time-consuming, and requiring special knowledge for data analysis.
      This study evaluated the potential of the DNA-sequence-based method to identify
      tree species and to quantify the relative proportion of each species in mixed
      fine root samples. We discriminated the species by isolating DNA from individual
      fine roots and amplifying the plastid trnL(UAA; i.e., tRNA-Leu-UAA) intron using
      the PCR. To estimate relative proportions, we extracted DNA from fine root
      mixtures. After the plastid trnL(UAA) intron amplification and TA-cloning, we
      sequenced the positive clones from each mixture. Our results indicated that the
      plastid trnL(UAA) intron spacer successfully distinguished tree species of fine
      roots in subtropical forests. In addition, the DNA-sequence-based approach could
      reliably estimate the relative proportion of each species in mixed fine root
      samples. To our knowledge, this is the first time that the DNA-sequence-based
      method has been used to quantify tree species proportions in mixed fine root
      samples in Chinese subtropical forests. As the cost of DNA-sequencing declines
      and DNA-sequence-based methods improve, the molecular method will be more widely
      used to determine fine root species and abundance. 

PMID- 25999975
TI  - RNA around the clock - regulation at the RNA level in biological timing.
AB  - The circadian timing system in plants synchronizes their physiological functions
      with the environment. This is achieved by a global control of gene expression
      programs with a considerable part of the transcriptome undergoing 24-h
      oscillations in steady-state abundance. These circadian oscillations are driven
      by a set of core clock proteins that generate their own 24-h rhythm through
      periodic feedback on their own transcription. Additionally, post-transcriptional
      events are instrumental for oscillations of core clock genes and genes in clock
      output. Here we provide an update on molecular events at the RNA level that
      contribute to the 24-h rhythm of the core clock proteins and shape the circadian
      transcriptome. We focus on the circadian system of the model plant Arabidopsis
      thaliana but also discuss selected regulatory principles in other organisms. 

PMID- 25999978
TI  - Early Cretaceous Archaeamphora is not a carnivorous angiosperm.
AB  - Archaeamphora longicervia H. Q. Li was described as an herbaceous, Sarraceniaceae
      like pitcher plant from the mid Early Cretaceous Yixian Formation of Liaoning
      Province, northeastern China. Here, a re-investigation of A. longicervia
      specimens from the Yixian Formation provides new insights into its identity and
      the morphology of pitcher plants claimed by Li. We demonstrate that putative
      pitchers of Archaeamphora are insect-induced leaf galls that consist of three
      components: (1) an innermost larval chamber; (2) an intermediate zone of
      nutritive tissue; and (3) an outermost wall of sclerenchyma. Archaeamphora is not
      a carnivorous, Sarraceniaceae-like angiosperm, but represents insect-galled
      leaves of the previously reported gymnosperm Liaoningocladus boii G. Sun et al.
      from the Yixian Formation. 

PMID- 25999979
TI  - Factors Related to Rejection of Care and Behaviors Directed towards Others: A
      Longitudinal Study in Nursing Home Residents with Dementia.
AB  - AIMS: The aim of this study was to analyze factors related to rejection of care
      and behaviors directed towards others in nursing home residents with dementia.
      METHODS: The relationship of lack of understanding, depression, psychosis and
      pain with rejection of care and behaviors directed towards others was explored
      using four assessments from the Minimum Data Set (MDS) within a period of 15
      months on 1,101 residents with dementia in Dutch nursing homes. Presence of
      depressive symptoms was ascertained using a validated MDS scale, and presence of
      lack of understanding, rejection of care, psychosis and pain through the
      individual MDS items. A structural equation modeling approach and latent growth
      models were used to investigate the longitudinal relationship between changes in
      rejection of care and physical or verbal behaviors directed towards others, and
      changes in lack of understanding, pain, depression and psychotic symptoms.
      RESULTS: Changes in lack of understanding predicted changes in rejection of care,
      and there was also a relationship between changes in depression and rejection of
      care. Changes of behaviors directed towards others were related to changes in
      lack of understanding and depression. Pain and behaviors directed towards others
      were unrelated, and psychosis was rather stable throughout. A mediation model
      suggested that the relationship of lack of understanding with behaviors directed
      towards others was mediated by rejection of care. CONCLUSION: These results
      indicate that lack of understanding and depression are important factors in
      development of rejection of care and behaviors directed towards others. The
      relationship between lack of understanding and behaviors directed towards others
      is mediated by rejection of care. Improvement in communication between residents
      and caregivers, and perhaps also effective treatment of depression may prevent or
      ameliorate these behaviors directed towards others.

PMID- 25999980
TI  - Differential effects of acetylcholinesterase inhibitors on clinical responses and
      cerebral blood flow changes in patients with Alzheimer's disease: a 12-month,
      randomized, and open-label trial.
AB  - BACKGROUND/AIMS: The present study evaluated the differences in treatment
      outcomes and brain perfusion changes among 3 types of acetylcholinesterase
      inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine). METHODS: This
      was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil,
      rivastigmine, or galantamine), parallel-group, 12-month clinical trial carried
      out in 55 patients with AD. RESULTS: At 6 months, the results of the Mini-Mental
      State Examination (MMSE) and the Trail Making Test (TMT)-Part A showed an
      improvement versus baseline in the donepezil treatment group. All groups showed a
      significant increase in regional cerebral blood flow (rCBF), mainly in the
      frontal lobe. Significant rCBF reduction was observed in the temporal lobe and
      cingulate gyrus in all 3 groups. CONCLUSION: AchEI treatment prevents the
      progression of cognitive impairment and increases the relative rCBF in the
      frontal lobe.

PMID- 25999981
TI  - The CERAD Neuropsychological Battery in Patients with Frontotemporal Lobar
      Degeneration.
AB  - BACKGROUND/AIMS: The diagnosis of frontotemporal lobar degeneration (FTLD) is
      based on neuropsychological examination in addition to clinical symptoms and
      brain imaging. There is no simple, validated, cognitive tool available in
      screening for FTLD. The Consortium to Establish a Registry for Alzheimer's
      Disease neuropsychological battery (CERAD-NB) was originally devised to identify
      the early cognitive changes related to Alzheimer's disease (AD). Our aim was to
      investigate the utility of the CERAD-NB in FTLD. METHODS: Patients with FTLD (n =
      95) and AD (n = 90) were assessed with the CERAD-NB, Trail Making Test parts A
      and B and single-letter Phonemic Fluency. RESULTS: FTLD patients were more
      severely impaired in the Verbal Fluency subtest in the CERAD-NB and Trail Making
      Test part A compared to AD patients. In addition, AD patients were more impaired
      in memory subtests compared to FTLD patients. CONCLUSION: The CERAD-NB may be a
      useful tool in screening for FTLD. Impaired performance in Verbal Fluency with
      moderately well-preserved Delayed Recall and Memory Tests may help in identifying
      patients with probable FTLD and discriminating FTLD from AD. Adding the Trail
      Making Test to the battery might enhance its value as a screening instrument for
      FTLD.

PMID- 25999982
TI  - Does the Order of Item Difficulty of the Addenbrooke's Cognitive Examination Add
      Anything to Subdomain Scores in the Clinical Assessment of Dementia?
AB  - BACKGROUND: The Addenbrooke's Cognitive Examination (ACE) is used to measure
      cognition across a range of domains in dementia. Identifying the order in which
      cognitive decline occurs across items, and whether this varies between dementia
      aetiologies could add more information to subdomain scores. METHOD: ACE-Revised
      data from 350 patients were split into three groups: Alzheimer's type (n = 131),
      predominantly frontal (n = 119) and other frontotemporal lobe degenerative
      disorders (n = 100). Results of factor analysis and Mokken scaling analysis were
      compared. RESULTS: Principal component analysis revealed one factor for each
      group. Confirmatory factor analysis found that the one-factor model fit two
      samples poorly. Mokken analyses revealed different item ordering in terms of
      difficulty for each group. CONCLUSION: The different patterns for each diagnostic
      group could aid in the separation of these different types of dementia.

PMID- 25999983
TI  - Exosomal lncRNA-p21 levels may help to distinguish prostate cancer from benign
      disease.
AB  - Exosomes are membranous vesicles containing various biomolecules including
      lncRNAs which are involved in cellular communication and are secreted from many
      cells including cancer cells. In our study, investigated the exosomal GAS5 and
      lincRNA-p21 lncRNA levels in urine samples from 30 patients with prostate cancer
      (PCa) and 49 patients with benign prostatic hyperplasia. Quantification of lncRNA
      molecules was performed by real-time PCR. We observed a significant difference in
      the exosomal lincRNA-p21 levels between PCa and BPH patients whereas the GAS5
      levels did not reveal a difference. Our data suggest that the discriminative
      potential of exosomal lincRNA-p21 levels may help to improve the diagnostic
      prediction of the malignant state for patients with PCa. 

PMID- 25999985
TI  - Normal findings on pretreatment transcranial ultrasound in patients treated with
      sonothrombolysis.
AB  - In populations with a high (>=14) median National Institute of Health Stroke
      Score (NIHSS), a normal finding of Thrombolysis in Brain Ischemia grade 5 (TIBI
      5) in the artery of interest has been reported to be an unusual finding when
      transcranial ultrasound is performed during thrombolysis. In such instances, a
      stroke mimic can be suspected, but there are alternative pathophysiological
      explanations. In this case series, the median NIHSS was relatively low (5), and
      33% (6/18) of the patients treated with thrombolysis had TIBI 5 in the artery of
      interest at the time of treatment initiation. These 6 patients had normal
      findings on the computerized tomography angiography. Only 33% (2/6) of these
      patients were stroke mimics, the remaining had either lacunar (n = 2) or cortical
      strokes (n = 2). These cortical stroke patients probably had a pretreatment
      recanalization marked by partial symptom regression before treatment onset.
      Compared to patients with TIBI <5 at baseline, the patients with TIBI 5 at
      baseline tended to be younger (p = 0.19, Mann-Whitney test) and more often have
      lacunar syndrome (p = 0.18, chi(2) test). Thus, among patients treated with
      thrombolysis and with a low median NIHSS, a finding of TIBI 5 is not unusual.
      This does not mean that the patient has a stroke mimic per se, and it tends to be
      more common among patients with lacunar syndrome than among patients with
      cortical syndromes. 

PMID- 25999984
TI  - Noncoding RNAs in human saliva as potential disease biomarkers.

PMID- 25999986
TI  - Intercavernous sinus dural arteriovenous fistula treated with transvenous coil
      embolization: a case report.
AB  - The blood supply to the region of the cavernous sinus is provided by
      interconnecting branches of the internal and external carotid arteries, and it is
      from these vessels that dural arteriovenous fistulas (DAVFs) arise. It is very
      rare that DAVFs are located at the intercavernous sinuses region; in this case, a
      proper localization of the fistulous site is of extreme importance in order to
      successfully eliminate the disease. Here, we describe a case of a 65-year-old
      female with intercavernous sinus DAVF. A complete obliteration of the fistulous
      points was performed by coil embolization through a transvenous approach. 

PMID- 25999988
TI  - Stent Placement for Severe Stenosis of the Left Common Carotid Artery with
      Internal-to-External Carotid Steal.
AB  - We report the case of a 64-year-old male with internal carotid artery (ICA)-to
      external carotid artery (ECA) steal due to severe stenosis of the common carotid
      artery (CCA). Left CCA occlusion was initially diagnosed on 3-dimensional time-of
      flight magnetic resonance angiography, but digital subtraction angiography
      revealed severe stenosis of the left CCA and retrograde flow through the left ICA
      feeding the left ECA. Diverted blood flow from ECA to ICA in cases with occlusion
      or severe stenosis of the CCA represents a well-known alternative collateral flow
      pattern called ECA-to-ICA steal. However, collateral flow from ICA to ECA is
      rarely observed and may be termed ICA-to-ECA steal. We treated CCA stenosis in
      our patient by carotid artery stenting (CAS) because his CCA stenosis had been
      gradually progressing since the initial ischaemic attack. Antegrade ICA flow
      subsequently recovered. To the best of our knowledge, this is the first report of
      ICA-to-ECA steal normalised by the treatment of CCA stenosis using CAS. 

PMID- 25999987
TI  - Hemodynamic changes and baroreflex sensitivity associated with carotid
      endarterectomy and carotid artery stenting.
AB  - Atherosclerotic carotid lesion is a major cause of stroke which accounts for up
      to 20% of ischemic stroke. Aggressive treatment of carotid stenosis may prevent
      stroke. Currently, carotid endarterectomy (CEA) and carotid artery stenting (CAS)
      are the first-line treatments for severe carotid stenosis. CEA is superior to
      medical therapy in preventing stroke and cardiovascular death. CAS has emerged as
      an alternative to CEA in recent years due to its less invasive nature. However,
      both CEA and CAS may be associated with adverse hemodynamic changes as well as a
      variation of carotid baroreflex sensitivity. There is no consensus on which of
      these two methods is more advantageous concerning the procedure-related
      hemodynamic changes. This article reviews the hemodynamic changes and baroreflex
      sensitivity after CEA and CAS. 

PMID- 25999989
TI  - Pulmonary arteriovenous malformation as a cause of embolic stroke: case report
      and review of the literature.
AB  - BACKGROUND: Pulmonary arteriovenous malformation (PAVM) is an abnormal
      communication between pulmonary arteries and veins responsible for right-to-left
      shunting that could induce the development of embolic stroke. SUMMARY: We
      describe an 82-year-old woman without history of respiratory or neurological
      diseases, who presented at our observation unit with acute onset of cerebral
      ischemia. Clinical, laboratory and radiological findings diagnosed a PAVM. KEY
      MESSAGES: Usually, endovascular procedures based on embolization or,
      alternatively, surgery represent the recommended treatment. However, both
      hormonal therapy and thrombolytic therapy can be used. In our patient, treatment
      with warfarin induced a remission of symptoms. This strategy should be tested in
      larger studies.

PMID- 25999990
TI  - Endovascular revascularization for basilar artery occlusion.
AB  - Basilar artery occlusion is one of the most devastating neurological conditions
      known to man. Though rare, patients with clinical syndromes localized to this
      anatomical region are often referred to acute stroke and endovascular units.
      Recent studies evaluating the efficacy of endovascular approaches to stroke have
      focused on anterior circulation syndromes. In this review, we examine the
      approaches to stroke syndromes due to basilar artery thrombosis. We share the
      relevant data for intravenous and intra-arterial tissue plasminogen activator as
      well as mechanical approaches to restoring perfusion in this critical area of the
      brain. 

PMID- 25999991
TI  - Endovascular Treatment of Proximal Aortic Arch Lesions through a Retrograde
      Approach.
AB  - Tandem atherosclerotic lesions of the carotid bifurcation and the ipsilateral
      proximal common carotid artery (CCA) or innominate arteries (IA) can be
      challenging to treat. A surgical approach may treat the lesion at the carotid
      bifurcation, but proximal CCA or IA lesions require a major surgical exposure. An
      endovascular approach is challenging as well since anatomic variations, such as a
      type III aortic arch, can render navigation very difficult. We report our
      experience in the hybrid surgical and endovascular treatment of complex proximal
      CCA and IA lesions. Eleven patients who underwent hybrid procedures with surgical
      exposure (with or without endarterectomy) of the carotid artery and retrograde
      endovascular intervention of a proximal lesion were included in the study. The
      mean percentage of stenosis was 81%. Seven patients underwent a carotid
      endarterectomy (CEA), and 4 patients underwent only a surgical cutdown for
      retrograde endovascular access of the IA or left CCA. All procedures were
      technically successful. Eight patients had no symptoms within 30 days of the
      procedure. The hybrid retrograde endovascular approach through carotid exposure
      with or without CEA appears to be effective and safe in selected patients who
      have a high-risk complex anatomy of tandem lesions. 

PMID- 25999992
TI  - Large deep white matter lesions may predict futile recanalization in endovascular
      therapy for acute ischemic stroke.
AB  - OBJECTIVE: This study investigated whether large ischemic lesions in the deep
      white matter (DWM) on pretreatment diffusion-weighted MRI (DWI) predict futile
      recanalization. METHODS: Consecutive acute stroke patients with anterior
      circulation ischemia who underwent successful arterial recanalization with
      thrombolysis in cerebral infarction grade 2b or 3 were enrolled. A large DWI-DWM
      lesion was defined as a hyperintense lesion in the DWM on initial DWI, located
      mainly between the anterior and posterior horns of the lateral ventricle. The
      Alberta Stroke Program Early CT score on CT and DWI and stroke volume on initial
      DWI were recorded. Stroke severity was assessed using the National Institutes of
      Health Stroke Scale (NIHSS) score. Futile recanalization was defined as a 30-day
      modified Rankin scale score of 3-6 despite successful recanalization. Univariate
      and multivariate regression analyses were performed to identify predictors of
      futile recanalization. RESULTS: In 35 of 46 patients (76%) with successful
      recanalization, futile recanalization was observed in 20 patients (57%). Patients
      with futile recanalization were older (median age 74 vs. 58 years; p = 0.053),
      had higher initial NIHSS scores (median 17 vs. 9; p = 0.042), and a higher
      prevalence of large DWI-DWM lesions (45 vs. 9%; p = 0.022). Logistic regression
      analysis showed that a large DWI-DWM lesion was an independent predictor of
      futile recanalization (OR 13.97; 95% CI 1.32-147.73; p = 0.028). CONCLUSION:
      Patients with large preintervention DWI-DWM lesions may be poor candidates for
      endovascular therapy.

PMID- 25999993
TI  - Aggressive medical care in young chinese patients with ischemic stroke of
      undetermined etiology: a retrospective study.
AB  - OBJECTIVES: This study aimed to investigate the clinical and angiographic
      characteristics of ischemic stroke of undetermined etiology in young Chinese
      adults and to observe the effects of medication on their long-term outcomes.
      METHODS: A total of 179 consecutive young patients with ischemic stroke of
      undetermined etiology were retrospectively analyzed for clinical and angiographic
      characteristics, laboratory tests, the choice of drug treatment, and follow-up
      outcomes. Any predictive power for recurrent stroke and new lesions or aggravated
      stenosis was analyzed. RESULTS: 170 patients were clinically followed up for a
      median of 25 months (range, 4-92), and 65 patients with 114 lesions had
      angiographic follow-up for a median of 7 months. A total of 53 patients were
      enrolled in a routine medical management (RMM) group, and 117 were treated with
      corticosteroids plus RMM (aggressive medical management, AMM). Kaplan-Meier
      survival analysis revealed that differences in the 2-year cumulative stroke-free
      rate and in the 18-month cumulative worsening and/or new lesion-free rate between
      the RMM and AMM groups were significant (p < 0.05). Multivariate and Cox
      regression analyses revealed that the choice of drug therapy and erythrocyte
      sedimentation rate were associated with recurrent stroke, that AMM was
      independently associated with a decreased risk of worsening lesion, and that
      worsening lesion was the only independent predictor of recurrent stroke.
      CONCLUSION: Compared with RMM, AMM is more efficacious in the prevention of
      secondary ischemic stroke and progressive arterial lesions among young adults
      with ischemic stroke of undetermined etiology.

PMID- 25999994
TI  - The impact of polycystic ovary syndrome on the health-related quality of life: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) has been shown to cause a reduction
      in health-related quality of life (HRQOL). However, the relative degree of
      impairment in each domain differed among samples, and it was not clear which
      aspect of disease-specific HRQOL (modified polycystic ovary syndrome health
      related quality of life questionnaire) was most negatively affected. OBJECTIVE:
      To systematically review the effects of PCOS on specific domains of HRQOL.
      MATERIALS AND METHODS: Literature search using search engine of database (PubMed,
      PsychInfo, CINAHL, CENTRAL, and Scopus) between 1998 to December 2013 yields 6
      relevant publications. Pairs of raters used structural tools to analyze these
      articles, through critical appraisal and data extraction. The scores of each
      domain of polycystic ovarian syndrome questionnaire (PCOSQ) or modified version
      (MPCOSQ) of 1140 women with PCOS were used in meta-analysis. RESULTS: The combine
      mean of emotional (4.40; 95% CI 3.77-5.04), infertility (4.13; 95% CI 3.81-4.45)
      and weight (3.88; 95% CI 2.33-5.42) dimensions were better, but menstruation
      (3.84; 95% CI 3.63-4.04) and hirsutism (3.81; 95% CI 3.26-4.35) domains were
      lower than the mean score of PCOSQ/MPCOSQ in related dimension. CONCLUSION: The
      meta-analysis showed that the most affected domains in specific HRQOL were
      hirsutism and menstruation. Based on these findings, we recommend healthcare
      providers to be made aware that HRQOL impairment of PCOS is mainly caused by
      their hirsutism and menstruation, which requires appropriate management.

PMID- 25999995
TI  - Influence of omega-3 fatty acid eicosapentaenoic acid on IGF-1 and COX-2 gene
      expression in granulosa cells of PCOS women.
AB  - BACKGROUND: The omega-3 (omega-3) fatty acid eicosapentaenoic acid (EPA) is
      currently used in the clinic as a nutritional supplement to improve infertility,
      particularly in women with polycystic ovarian syndrome (PCOS). OBJECTIVE: The
      present study was designed to investigate the effect of EPA on insulin-like
      growth factor 1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression in primary
      cultured granulosa cells from patients undergoing in vitro fertilization (IVF),
      and also to compare this effect with those in granulosa cells of PCOS patients.
      MATERIALS AND METHODS: In this experimental study, human granulosa cells were
      isolated from follicular fluid of normal and PCOS women undergoing IVF by
      hyaluronidase digestions, followed by Percoll gradient centrifugation. Cells were
      cultured in vitro, exposed to a range of concentrations of the EPA (25-100 uM)
      for 24 hr, and investigated with respect to COX-2 and IGF-1 gene expression by
      real time-PCR. RESULTS: In both groups, all doses of the EPA significantly
      induced IGF-1 mRNA gene expression compared to the untreated control. High doses
      of EPA in the presence of recombinant (r) FSH produced a stimulatory effect on
      IGF-1 and a suppressive effect (p=0.01) on the COX-2 gene expression, which were
      more pronounced in granulosa cells from PCOS patients. CONCLUSION: EPA affect
      diversely the gene expression of IGF-1 and COX-2 in granulosa cells, which were
      more pronounced in PCOS compared to control. These findings represent the
      possible underlying molecular mechanisms for the positive impact of the omega-3
      fatty acids on reproduction, especially in patients with PCOS.

PMID- 25999996
TI  - Premature progesterone rise at human chorionic gonadotropin triggering day has no
      correlation with intracytoplasmic sperm injection outcome.
AB  - BACKGROUND: Premature luteinization during in vitro fertilization was commonly
      happened before the introduction of GnRh analogues. High level of unwanted
      progesterone is associated with adverse pregnancy outcome and is thought to be
      induced by inappropriate LH elevation. OBJECTIVE: To evaluate the progesterone
      level on the day of Human Chorionic Gonadotropin (HCG) triggering in GnRh agonist
      and antagonist protocols, and its correlation with clinical pregnancy rate and
      miscarriage rate. MATERIALS AND METHODS: One hundred and seven women underwent
      intracytoplasmic sperm injection with long agonist protocol (n=46) or antagonist
      protocol (n=61). Blood sample was obtained from each patient for progesterone
      level measurement in HCG administration day, then patients were divided into two
      groups according to their serum progesterone levels on the HCG triggering day:
      progesterone level <1.2 ng/ml, and progesterone level >=1.2 ng/ml. Clinical
      pregnancy and miscarriage rates were evaluated as main outcomes and biochemical
      pregnancy rate and implantation rate were considered as secondary outcomes.
      RESULTS: The increased prevalence rate of premature progesterone (progesterone
      level >=1.2 ng/ml) in total patients was 13.1% (14/107) and in long agonist
      protocol group and antagonist protocol group was 15.2% (7/46) and 11.5% (7/61)
      respectively. Premature progesterone rise had no significant correlation with
      clinical pregnancy rate in total patients (p=0.174), agonist protocol (p=0.545),
      and antagonist protocol (p=0.129). Also premature progesterone rise had no
      significant association with miscarriage rate in total patients (p=0.077),
      agonist protocol group (p=0.383) and antagonist protocol group (p=0.087).
      CONCLUSION: A significant rise in progesterone levels at the time of HCG
      triggering doesn't lead to decrease in pregnancy rate and implantation rate and
      increase in miscarriage rate.

PMID- 25999997
TI  - Effects of Ghrelin on germ cell apoptosis and proinflammatory cytokines
      production in Ischemia-reperfusion of the rat testis.
AB  - BACKGROUND: Testicular torsion is a medical emergency that requires surgical
      intervention to reperfuse the affected testis. Ischemia reperfusion injury is
      usually associated with proinflammatory cytokine generation and apoptosis of germ
      cells in the testes. OBJECTIVE: In this study we investigate the effect of
      ghrelin on the proinflammatory cytokines levels and germ cell apoptosis in
      testicular ischemia reperfusion. MATERIALS AND METHODS: 45 male rats were
      selected for the study and randomly divided into 3 groups, each containing 15
      rats. Animals in the testicular torsion and ghrelin treated groups were subjected
      to unilateral 720 counterclockwise testicular torsion for 1 hr and then
      reperfusion was allowed after detorsion for 4 hr, 1 and 7 days. The ghrelin
      treated group received intraperitoneal injection of ghrelin 15min before
      detorsion. The expression levels of bcl-2-associated X protein and proliferating
      cell nuclear antigen in testicular tissue in the different groups were detected
      by immunohistochemical assay and tissue cytokines interleukin-1beta, tumor
      necroses factor-alpha and interleukin-6 were measured using enzyme-linked
      immunosorbent assay. RESULTS: After being treated by ghrelin, the population of
      immunoreactive cells against BAX in the spermatocytes on day 7 after reperfusion
      significantly decreased when compared to tortion/ detortion-saline animals
      (p=0.024). In contrast, PCNA expression in the spermatocytes and spermatogonia
      were not significantly different between tortion/ detortion-ghrelin and tortion/
      detortion-saline groups on both experimental days. Administration of ghrelin
      significantly attenuated the testicular tumor necroses factor-alpha and
      interleukin-6 levels compared with the untreated animals, but had no significant
      effect on the level of interleukin-1beta. CONCLUSION: Ghrelin offers remarkable
      anti-inflammatory and anti-apoptotic effects in testicular ischemia reperfusion
      injury.

PMID- 25999998
TI  - Cabergoline plus metformin therapy effects on menstrual irregularity and androgen
      system in polycystic ovary syndrome women with hyperprolactinemia.
AB  - BACKGROUND: 30% of patients with polycystic ovary syndrome (PCOS) show mild,
      transient hyperprolactinemia. It is suggested that a reduction of the dopamine
      inhibitory effect might raise both prolactin and luteinizing hormone. OBJECTIVE:
      To investigate the adjuvant cabergoline therapy effects on menstrual irregularity
      and androgen system in PCOS women with hyperprolactinemia. MATERIALS AND METHODS:
      This randomized clinical trial was done on 110 polycystic ovary syndrome women
      with increased serum prolactin concentration [1.5 fold more than normal level
      (>37.5 ng/ml)]. Participants were divided into two groups: Case group (n=55)
      treated with metformin 1gr/day and cabergoline 0.5 mg/week for 4 months and
      control group (n=55) treated with metformin 1g/day and placebo weekly.
      Testosterone, prolactin, and dehydroepiandrosterone sulfate level were measured
      before and four months after intervention in two groups. Also, situation of
      menstrual cycles asked and recorded before and after intervention. RESULTS: We
      found decrease in the mean of dehydroepiandrosterone sulfate, weight and total
      testosterone level in the two groups after intervention but their changes were
      not significant. Patients in case group showed a significant decrease in serum
      prolactin level before and after intervention (p<0.001), but no difference was
      found in control group. All patients in both studied groups had irregular
      menstrual cycles, which regulate after intervention and the difference was
      significant (p=0.02). CONCLUSION: The results showed that cabergoline can be used
      as a safe administration in PCOS patients with hyperprolactinemia to improve the
      menstrual cycles. Considering that the administration of cabergoline plus
      metformin may reduce the required duration and dose of metformin, patient
      acceptability of this approach is higher.

PMID- 25999999
TI  - Predictive value of maternal serum beta-hCG concentration in the ruptured tubal
      ectopic pregnancy.
AB  - BACKGROUND: Measurement of serum beta-hCG concentration commonly used to diagnose
      tubal ectopic pregnancy (EP) and follow up patients treated conservatively.
      OBJECTIVE: The aim of this study was to determine the predictive value of
      maternal serum beta-hCG concentration in ruptured tubal ectopic pregnancy to help
      physicians identify those women who are at greatest risk. MATERIALS AND METHODS:
      This is a cross-sectional study conducted on all women with a diagnosis of tubal
      ectopic pregnancy who were treated in Alzahra Hospital, in Rasht, from March 2002
      to February 2011. The data was collected for each woman from medical records and
      included age, parity, gravidia, gestational age, primary level of serum beta-hCG,
      rupture status, past history of pelvic inflammation disease, EP, abortion, and
      intrauterine contraceptive device use. Women with tubal rupture were compared to
      those without rupture. Statistical analysis was conducted by SPSS 19 for Windows.
      RESULTS: A total of 247 cases of tubal ectopic pregnancy were recorded during the
      study period. One hundred and ninety seven (79.8%) were cases with unruptured EP
      and 50 patients (20.2 %) were cases with ruptured EP. The mean level of beta-hCG
      was significantly higher in patients with ruptured EP compared to patients with
      unruptured EP (p=0.03). Logistic regression analysis revealed that >1750 IU/ml of
      beta-hCG levels (OR: 1.41; 95% CI: 1.18-1.68) was the significant risk factors
      for tubal rupture. CONCLUSION: Higher beta-hCG levels seem to be significant risk
      factors for rupture of a tubal EP.

PMID- 26000000
TI  - CPITN changes during pregnancy and maternal demographic factors 'impact on
      periodontal health.
AB  - BACKGROUND: There have been speculations about the effects of hormonal changes
      and socio-demographic factors on periodontal health during pregnancy. OBJECTIVE:
      According to the lack of sufficient epidemiologic information about the
      periodontal status of pregnant women in Yazd, this study was accomplished to
      determine the changes of Community Periodontal Index for Treatment Needs (CPITN)
      during pregnancy and evaluating the possible relationship between this index and
      demographic characteristics of the mothers. MATERIALS AND METHODS: This was a
      longitudinal descriptive study. The samples included 115 pregnant women who were
      referred to health centers of Yazd, Iran. The mothers' data were obtained from a
      questionnaire consisted of 3 parts: consent paper, demographic data and CPITN
      records. Examination was performed with dental unit light, flat dental mirror and
      WHO's scaled probe. RESULTS: In the beginning of the study, 60.1% of checked
      sextants had healthy gingival status. 25.9% had code1 and 14% had code 2. Code 3
      and 4 were not seen in any sextants. There was a significant relationship between
      lower CPITN and higher maternal education, occupation and more frequencies of
      tooth-brushing but there was not a relationship between CPITN and mother's age
      and number of pregnancies. CPITN had a significant relationship with increasing
      of the gestational age. CONCLUSION: There might be a relationship between
      increasing the month of pregnancy and more periodontal treatment needs. CPITN
      Increasing during pregnancy shows the importance of periodontal cares during this
      period.

PMID- 26000001
TI  - A successful pregnancy during the treatment of cervical sarcoma botryoides and
      advantage of fertility sparing management: A case report.
AB  - BACKGROUND: Sarcoma botryoides of cervix is a rare variant of rhabdomyosarcomas
      (RMS) of female genital tract. It is usually diagnosed in first or second decade
      of life. In this case report, we aimed to present a 21 year-old nulligravid
      patient who was diagnosed with embryonal RMS of the cervix, to discuss the
      treatment options that have been stated in the literature, and to highlight the
      advantage of fertility sparing management in these young patients. CASE: We
      report a 21-year-old nulligravid woman complaining about a mass protruding from
      introitus, which was represented with a 8*7 cm "grape-like" cervical polyp on
      speculum examination. The histopathologic examination of the biopsy taken was
      combined with immunohistochemical staining with desmin, myogenin, S100, vimentin,
      and myoglobin. Colposcopy, second biopsy, and positron emission tomography were
      used during the follow-up. The histopathologic examination revealed embryonal RMS
      of cervix. She received three cycles of combination chemotherapy, doxorubicin and
      ifosfamide. She refused to have a surgery because of an unplanned, desired
      pregnancy at two months after the chemotherapy. She was lost during the follow
      up. After having an uneventful pregnancy and a successful delivery, she reapplied
      at postpartum 6(th) month. Colposcopic evaluation revealed a local polypoid area,
      the histopathologic examination of biopsy suggested recurrence even though
      positron emission tomography scans were unremarkable. Therefore complementary
      treatment was planned as conization and pelvic lymphadenectomy. The
      histopathology revealed no residual tumor on the conization material and no
      involvement of pelvic lymph nodes. CONCLUSION: Fertility sparing management,
      including doxorubicin and ifosfamid combination in chemotherapy step, can be
      management option. Pregnancy and successful delivery is possible during the
      treatment. Colposcopy has importance for early detection of recurrences.

PMID- 26000002
TI  - Assessment on the adverse effects of Aminoglycosides and Flouroquinolone on sperm
      parameters and male reproductive tissue: A systematic review.
AB  - BACKGROUND: Antibiotic therapies used in treatment of many diseases have adverse
      effects on fertility. This review analyzes previous comparative studies that
      surveyed the effects of two common groups of antibiotics on male fertility.
      OBJECTIVE: To evaluate histo-pathological effects of fluoroquinolones and
      aminoglycosides on sperm parameters and male reproductive tissue. MATERIALS AND
      METHODS: Articles about the effects of aminoglycosides and fluoroquinolones on
      male infertility, sperm parameters, male reproductive tissue, and spermatogenesis
      in English and Persian languages published on Google Scholar and PubMed databases
      from January 2000 to December 2013 were assessed. Randomized controlled trials
      (RCTs) assessing the effects of aminoglycosides or fluoroquinolones on sperm
      parameters, artificial insemination, and male reproductive tract or RCTs
      comparing aminoglycosides vs. fluoroquinolones were eligible for inclusion. For
      ascertaining the reliability of study, data were extracted independently and in
      duplicate by two investigators. RESULTS: Sperm viability was decreased
      significantly with streptomycin, gentamicin, and neomycin (p<0.001). Sperm
      motility was decreased significantly with gentamicin and neomycin (p<0.05). Total
      sperm count was significantly decreased with ofloxacin, gentamicin, streptomycin,
      and neomycin (p<0.022). There was significant decrease in post-thawing motility
      with low dose and high dose of ciprofloxacin. Testis weight was decreased with
      gentamicin and ofloxacin significantly (p<0.011). There was significant decrease
      in seminal vesicle weight with gentamicin, neomycin, and ofloxacin (p<0.022).
      Furthermore, changes in epididymis weight, percentage of total apoptotic cells,
      and diameter of seminiferous tubule were significant with all drugs including
      streptomycin, gentamicin, neomycin, and ofloxacin (p<0.05). CONCLUSION:
      Streptomycin has less negative effects on cell's apoptosis and sperm parameters
      as compared to other drugs. Gentamicin has more detrimental effects so lesser
      dosage and duration is recommended. Fluoroquinolones showed negative effects on
      testis tissue and sperm parameters. Ciprofloxacin has less adverse effects than
      gentamicin in artificial insemination.

PMID- 26000003
TI  - Types of reproductive disorders in underweight and overweight young females and
      correlations of respective hormonal changes with BMI.
AB  - BACKGROUND: Higher risks of reproductive problems have been found in underweight
      and overweight women with rapid weight gain or loss but evidence is inconsistent
      especially in relation to the effect of age of body weight changes. OBJECTIVE:
      The aim of our study was to detect the peculiarities of menstrual function,
      prevalence of different types of reproductive disorders and correlations of
      respective hormonal changes with body mass index (BMI) in young female patients
      with thinness or obesity since childhood. MATERIALS AND METHODS: In this
      prospective cross-sectional study 48 underweight and 55 overweight/obese young
      women with different reproductive problems underwent complete clinical and
      hormonal analyses. All 103 patients had weight problems since childhood. RESULTS:
      Polycystic ovarian syndrome and metabolic syndrome was the most frequent in
      overweight and obese women, whilst non-classical congenital adrenal hyperplasia
      and ovarian dysfunction prevailed in underweight women (p?0.001). No difference
      was determined according to the age of menarche (p=0.885) and types of menstrual
      disturbances (p=0.34) between the study groups. Hypogonadotropic hypogonadism was
      not found in young women who were lean since childhood. Follicle-stimulating
      hormone (FSH) (p=0.013) and sex hormone binging globulin (SHBG) (p?0.001) levels
      were higher in women with low BMI, whilst free testosterone (FT) (p=0.019) and
      total testosterone (TT) (p=0.003) levels were higher in high BMI participants.
      BMI negatively correlated with FSH (p=0.009) and SHBG (p=0.001); and positively
      correlated with FT (p=0.001) and TT (p=0.002). CONCLUSION: Peculiarities of
      menstrual function and hormonal changes in young women with thinness or obesity
      since childhood are related to the types of reproductive disorders and their
      childhood BMI.

PMID- 26000004
TI  - The viability of mouse spermatogonial germ cells on a novel scaffold, containing
      human serum albumin and calcium phosphate nanoparticles.
AB  - BACKGROUND: In spermatogenesis, spermatogonial cells differentiate to the haploid
      gametes. It has been shown that spermatogenesis can be done at in vitro
      condition. In vitro spermatogenesis may provide an open window to treat male
      infertility. OBJECTIVE: The aim of this study was to evaluate the effects of a
      novel scaffold containing human serum albumin (HSA)/tri calcium phosphate
      nanoparticles (TCP NPs) on the mouse spermatogonial cell line (SCL). MATERIALS
      AND METHODS: First, TCP NPs were synthesized by reaction of calcium nitrate and
      diammonium phosphate at pH 13. Then, serial concentrations of TCP NPs were
      separately added to 500 mg/mL HSA, and incubated in the 100(o)C water for 30 min.
      In the next step, each scaffold was cut (2*2mm), placed into sterile well of
      microplate, and then incubated for 1, 2, and 3 days at 37(o)C with mouse SCL.
      After incubation, the cytotoxicity of the scaffolds was evaluated by different
      tests including 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide
      (MTT) assay, lactate dehydrogenase (LDH) assay, vital staining, and cell
      counting. On the other hand, the release of TCP NPs and HSA from the scaffolds
      was measured. RESULTS: Based on microscopic observation, the size of cavities for
      all scaffolds was near 200-500 um, and the size of TCP NPs was near 50-100 nm.
      All toxicity tests showed that the increase of TCP concentration in the scaffold
      did not affect mouse SCL. It means that the percentage of cell viability, LDH
      release, vital cells, and cell quantity was 85%, 105%, 90%, and 110%,
      respectively. But, the increase of incubation time led to increase of LDH release
      (up to 115%) and cell count (up to 115%). Also, little decrease of cell viability
      and vital cells was seen when incubation time was increased. Here, no release of
      TCP NPs and HSA was seen after increase of TCP concentration and incubation time.
      CONCLUSION: It can be concluded that the increase of TCP concentration in HSA/
      TCP NPs scaffold does not lead to cytotoxicity. On the other hand, the increase
      of incubation time leads to increase of mouse SCL cell death. In this study, it
      was found that TCP NPs and HSA could not release from the scaffolds. In future,
      both proliferation and differentiation of mouse SCL on HSA/TCP NPs scaffold must
      be checked over more wide incubation times.

PMID- 26000005
TI  - Comparison of anti-mullerian hormone level in non-endometriotic benign ovarian
      cyst before and after laparoscopic cystectomy.
AB  - BACKGROUND: Benign ovarian cysts are common among both pre- and postmenstrual
      women. Surgical intervention for excision of an ovarian cyst is mandated when
      symptomatic, or chance for malignancy is high. The damaging effect of surgical
      ovarian cystectomy on ovarian reserve is debated in recent studies. OBJECTIVE: In
      the present study we investigated serum level of anti-mullerian hormone (AMH) as
      an indicator of ovarian reserve before and after surgical cystectomy. MATERIALS
      AND METHODS: 60 patients with dermoid cyst, serous cystadenoma, and mucinous
      cystadenoma were recruited. Measurement of serum AMH was performed prior to
      surgery, and at one and 3 months after laparoscopic cystectomy. Serum AMH levels
      were compared before and after the surgery and between various types of ovarian
      cyst. RESULTS: Serum AMH level declined significantly after the surgery which
      recovered to 65% of its baseline value three months later. CONCLUSION: Decreased
      serum AMH can be contributed to decreased ovarian reserve after laparoscopic
      ovarian cystectomy. This can result from thermo-coagulation used for hemostasis
      during the operation.

PMID- 26000006
TI  - Association between endometriosis and hyperprolactinemia in infertile women.
AB  - BACKGROUND: The association of endometriosis with hyperprolactinemia is
      controversial. OBJECTIVE: The present study aimed to determine the frequency of
      endometriosis and association of prolactin with endometriosis in infertile women.
      MATERIALS AND METHODS: 256 infertile women who underwent diagnostic laparoscopy
      for the evaluation of infertility, referred to Fatemezahra Infertility and
      Reproductive Health Research Center were included in a cross-sectional study. The
      presence of endometriosis was evaluated. To investigate the association of
      endometriosis with hyperprolactinemia, the patients whose infertility was not
      caused by endometriosis were included as control group. Serum prolactin (PRL)
      level was measured in both groups. The comparison of basal serum PRL levels
      between the two groups was performed, using independent t-test. One way ANOVA was
      used to determine PRL association with endometriosis stages. RESULTS: The
      frequency of endometriosis was found to be 29%. PRL levels were significantly
      higher in endometriosis group compared to control group (23.02+/-1.25 vs. 17.22+/
      1.22 respectively, p=0.004). Statistically significant associations were found
      between staging of endometriosis and prolactin levels (p=0.01). CONCLUSION:
      Hyperprolactinemia may be associated with endometriosis and its progression.

PMID- 26000007
TI  - Intrauterine synechiae after myomectomy; laparotomy versus laparoscopy: Non
      randomized interventional trial.
AB  - BACKGROUND: Leiomyomata is the most frequent gynecological neoplasm. One of the
      major complications of myomectomy is intrauterine adhesion (synechiae).
      OBJECTIVE: To evaluate and compare the rate and severity of synechiae formation
      after myomectomy by laparotomy and laparoscopy. MATERIALS AND METHODS: In this
      non-randomized interventional trial, hysteroscopy was performed in all married
      fertile women who had undergone myomectomy (type 3-6 interamural and subserosal
      fibroids) via laparotomy and laparoscopy in Tehran's Arash Hospital from 2010 to
      2013. Three months after the operation, the occurrence rate and severity of
      intrauterine synechiae, and its relationship with type, number and location of
      myomas were investigated and compared in both groups. RESULTS: Forty patients (19
      laparoscopy and 21 laparotomy cases) were studied. Both groups were similar
      regarding the size, type (subserosal or intramural), number and location of
      myoma. The occurrence rate of synechiae in the laparoscopy and laparotomy group
      was 21% and 19%, respectively; showing no significant difference (p=0.99). Among
      all patients, no significant relationship was found between the endometrial
      opening (p=0.92), location (p=0.14) and type of myoma (p=0.08) with the
      occurrence rate of synechiae. However, a significant relationship was observed
      between myoma's size (p=0.01) and the location of the largest myoma with the
      occurrence of synechiae (p=0.02). CONCLUSION: With favorable suturing methods,
      the outcome of intrauterine synechiae formation after myomectomy, either
      performed by laparotomy or laparoscopy, is similar. In all cases of myomectomy in
      reproductive-aged women, postoperative hysteroscopy is highly recommended to
      better screen intrauterine synechiae.

PMID- 26000009
TI  - Neonatal diagnosis of 49, XXXXY syndrome.
AB  - BACKGROUND: 49, XXXXY syndrome is a rare sex chromosomal disorder, occurring in 1
      per 85,000-100,000 male births. The classical phenotype is ambiguous genitalia,
      facial dysmorphism, mental retardation and a combination of cardiac, skeletal and
      other malformations. CASE: A two month-old boy with intrauterine growth
      restriction (IUGR) and low birth weight, facial dysmorphism, clinodactyly in
      feet, microphallus, and right undescendent testis were seen by neonatologist.
      Chromosomal studies via techniques of GTG-banding showed the constitution to be
      49,XXXXY in all cells. He was visited by the pediatric cardiologist for
      congenital heart disease. No obvious malformation and congenital heart disease
      were seen. CONCLUSION: In the case, the main presentation of IUGR and low birth
      weight, clinodactyly with facial dysmorphism and genital abnormalities led to a
      suspicion of a sex chromosome aneuploidy which was subsequently confirmed by
      chromosomal analysis.

PMID- 26000008
TI  - Association of assisted reproductive technology with adverse pregnancy outcomes.
AB  - BACKGROUND: More and more infertile patients have accepted the assisted
      reproductive technique (ART) therapy. Concerns have been raised over an increased
      risk of adverse maternal outcomes in ART populations as compared with natural
      conception (NC). OBJECTIVE: The aim was to improve the ART in clinicial work and
      to reduce the incidence of pregnancy complications in ART group according to
      analyzing the reasons of high incidence of pregnancy complications in ART group,
      comparing the incidence of pregnancy complications in different controlled
      ovarian hyperstimulation (COH) programs and evaluating the effects of ART which
      attribute to adverse pregnancy outcomes. MATERIALS AND METHODS: In this
      prospective population-based cohort study,3216 pregnant women with gestational
      age <=12 weeks, regular antenatal examination,and ultrasound identification of
      intrauterine pregnancy were enrolled from January 2010 to June 2013. According to
      having ART history, the participantswere divided into two groups: ART group
      (contains fresh embryo transfer group or frozen-thawed embryo transfer group) and
      NC group. We compared the incidence of pregnancy complications between different
      groups and evaluated the factors which could affect the occurrence of these
      complications. RESULTS: When compared to NC group, significantly increased rates
      of gestational diabetes mellitus (GDM) (p<0.01), preeclampsia (PE) (p<0.01) and
      intrahepatic cholestasis of pregnancy (ICP) (p?0.01) were observed in ART group.
      There was no significant difference in the incidence of birth defect between the
      two groups (p=0.07). Multiple pregnancies and Gonadotropin (Gn) were risk factors
      in GDM, PE, and ICP. The exogenous progesterone treatment had no effect on GDM,
      PE or ICP. CONCLUSION: ART increases the risk of adverse maternal complications
      such as GDM, PE and ICP. The dosages of Gn should be reduced to an extent and the
      number of embryo implantation should be controlled. Exogenous progesterone
      treatment is safe.

PMID- 26000010
TI  - Image processing algorithms and measures for the analysis of biomedical imaging
      systems applications.

PMID- 26000011
TI  - Forecasting nonlinear chaotic time series with function expression method based
      on an improved genetic-simulated annealing algorithm.
AB  - The paper proposes a novel function expression method to forecast chaotic time
      series, using an improved genetic-simulated annealing (IGSA) algorithm to
      establish the optimum function expression that describes the behavior of time
      series. In order to deal with the weakness associated with the genetic algorithm,
      the proposed algorithm incorporates the simulated annealing operation which has
      the strong local search ability into the genetic algorithm to enhance the
      performance of optimization; besides, the fitness function and genetic operators
      are also improved. Finally, the method is applied to the chaotic time series of
      Quadratic and Rossler maps for validation. The effect of noise in the chaotic
      time series is also studied numerically. The numerical results verify that the
      method can forecast chaotic time series with high precision and effectiveness,
      and the forecasting precision with certain noise is also satisfactory. It can be
      concluded that the IGSA algorithm is energy-efficient and superior. 

PMID- 26000012
TI  - Endothelial dysfunction correlates with liver fibrosis in chronic HCV infection.
AB  - Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities
      due to its direct action on vessel walls and/or via the chronic inflammatory
      process involving the liver. Aims. To clarify the role of HCV in atherosclerosis
      development in monoinfected HCV patients at different degrees of liver fibrosis
      and with no risk factors for coronary artery disease. Methods. Forty-five
      patients were included. Clinical, serological, and anthropometric parameters,
      liver fibrosis (transient liver elastometry (fibroscan) and aspartate
      aminotransferase to platelet ratio index (APRI)), carotid intima-media thickness
      (c-IMT), and brachial artery flow-mediated vasodilatation (FMD) were assessed.
      Patients were divided into 3 tertiles according to fibroscan values. Results.
      Patients in the third tertile (fibroscan value >11.5 KPa) showed FMD values were
      significantly lower than second and first tertiles (4.7 +/- 1.7% versus 7.1 +/-
      2.8%, p = 0.03). FMD values were inversely related to liver elastomeric values. c
      IMT values were normal. The risk for endothelial dysfunction development in the
      third tertile (p = 0.02) was 6.9 higher than the first tertile. A fibroscan value
      >11.5 KPa had a positive predictive power equal to 79% for endothelial
      dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by
      inducing endothelial dysfunction independently of common cardiovascular risk
      factors. 

PMID- 26000013
TI  - Therapeutic targeting of fibroblast growth factor receptors in gastric cancer.
AB  - Chemotherapy has become the global standard treatment for patients with
      metastatic or unresectable gastric cancer (GC), although outcomes remain
      unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of
      various tyrosine kinase receptors have been developed, and monoclonal antibodies
      targeting human epidermal growth factor receptor 2 (HER2) have become standard
      therapy for HER2-positive GC. An inhibitor of vascular endothelial growth factor
      receptor 2 or MET has also produced promising results in patients with GC.
      Fibroblast growth factor receptors (FGFR) play key roles in tumor growth via
      activated signaling pathways in GC. Genomic amplification of FGFR2 leads to the
      aberrant activation found in GC tumors and is related to survival in patients
      with GC. This review discusses the clinical relevance of FGFR in GC and examines
      FGFR as a potential therapeutic target in patients with GC. Preclinical studies
      in animal models suggest that multitargeted tyrosine kinase inhibitors (TKIs),
      including FGFR inhibitor, suppress tumor cell proliferation and delay tumor
      progression. Several TKIs are now being evaluated in clinical trials as treatment
      for metastatic or unresectable GC harboring FGFR2 amplification. 

PMID- 26000014
TI  - Critical appraisal of international guidelines for the management of diabetic
      neuropathy: is there global agreement in the internet era?
AB  - Purpose. The management of diabetic neuropathy (DN) can be challenging. There
      exist many guidelines for DN management, but the quality of these guidelines has
      not been systematically evaluated or compared. The objective of our study was to
      assess the quality of these guidelines as a step toward their future
      optimization, the development of international guidelines, and, ultimately, the
      improvement of the care process. Methods. Relevant data were selected to identify
      international guidelines. The Appraisal of Guidelines for Research and Evaluation
      II (AGREE II) tool was used to evaluate the quality of the selected guidelines.
      In addition, the reviewers summarized and compared all of the recommendations
      from the included guidelines for DN's management. Results. Thirteen guidelines
      were included after the selection process. According to AGREE II, few guidelines
      scored well for all three aspects of DN management. Detailed comparisons revealed
      that these guidelines provide inconsistent recommendations, making it difficult
      for diabetes clinicians to choose appropriate guideline. Conclusions. The quality
      of most guidelines for the management of DN should be improved. Further studies
      should concentrate on developing internationally accepted and evidence-based
      guidelines that could be used for clinical decision making to improve patient
      care. 

PMID- 26000015
TI  - The relevance of the Renin-Angiotensin system in the development of drugs to
      combat preeclampsia.
AB  - Preeclampsia is a hypertensive disorder that occurs during pregnancy. It has an
      unknown etiology and affects approximately 5-8% of pregnancies worldwide. The
      pathophysiology of preeclampsia is not yet known, and preeclampsia has been
      called "a disease of theories." The central symptom of preeclampsia is
      hypertension. However, the etiology of the hypertension is unknown. In this
      review, we analyze the molecular mechanisms of preeclampsia with a particular
      focus on the pathogenesis of the hypertension in preeclampsia and its association
      with the renin-angiotensin system. In addition, we propose potential alternative
      strategies to target the renin-angiotensin system, which is enhanced during
      pregnancy. 

PMID- 26000017
TI  - Rapid identification of pathogens in positive blood culture of patients with
      sepsis: review and meta-analysis of the performance of the sepsityper kit.
AB  - Sepsis is one of the leading causes of deaths, and rapid identification (ID) of
      blood stream infection is mandatory to perform adequate antibiotic therapy. The
      advent of MALDI-TOF Mass Spectrometry for the rapid ID of pathogens was a major
      breakthrough in microbiology. Recently, this method was combined with extraction
      methods for pathogens directly from positive blood cultures. This review
      summarizes the results obtained so far with the commercial Sepsityper sample
      preparation kit, which is now approved for in vitro diagnostic use. Summarizing
      data from 21 reports, the Sepsityper kit allowed a reliable ID on the species
      level of 80% of 3320 positive blood culture bottles. Gram negative bacteria
      resulted consistently in higher ID rates (90%) compared to Gram positive bacteria
      (76%) or yeast (66%). No relevant misidentifications on the genus level were
      reported at a log(score)cut-off of 1.6. The Sepsityper kit is a simple and
      reproducible method which extends the MALDI-TOF technology to positive blood
      culture specimens and shortens the time to result by several hours or even days.
      In combination with antibiotic stewardship programs, this rapid ID allows a much
      faster optimization of antibiotic therapy in patients with sepsis compared to
      conventional workflows. 

PMID- 26000016
TI  - Circadian Clocks and the Interaction between Stress Axis and Adipose Function.
AB  - Many physiological processes and most endocrine functions show fluctuations over
      the course of the day. These so-called circadian rhythms are governed by an
      endogenous network of cellular clocks and serve as an adaptation to daily and,
      thus, predictable changes in the organism's environment. Circadian clocks have
      been described in several tissues of the stress axis and in adipose cells where
      they regulate the rhythmic and stimulated release of stress hormones, such as
      glucocorticoids, and various adipokine factors. Recent work suggests that both
      adipose and stress axis clock systems reciprocally influence each other and
      adrenal-adipose rhythms may be key players in the development and therapy of
      metabolic disorders. In this review, we summarize our current understanding of
      adrenal and adipose tissue rhythms and clocks and how they might interact to
      regulate energy homoeostasis and stress responses under physiological conditions.
      Potential chronotherapeutic strategies for the treatment of metabolic and stress
      disorders are discussed. 

PMID- 26000018
TI  - Intravenous iron administration and hypophosphatemia in clinical practice.
AB  - Introduction. Parenteral iron formulations are frequently used to correct iron
      deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation
      efficacy on ferritin and hemoglobin level improvement is greater than that of
      oral formulations while they are associated with lower gastrointestinal side
      effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and
      appears without clinical significance. The aim of this study was to assess the
      prevalence, duration, and potential consequences of hypophosphatemia after iron
      injection. Patients and Methods. The medical records of all patients who
      underwent parenteral iron injection between 2012 and 2014 were retrospectively
      reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate,
      creatinine, and vitamin D levels were assessed. Patients who developed moderate
      (range: 0.32-0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were
      questioned for symptoms. Results. During the study period, 234 patients received
      iron preparations but 104 were excluded because of missing data. Among the 130
      patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among
      FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated
      patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia
      severity correlated with the dose of FCM (p = 0.04) but not with the initial
      ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6
      months. No immediate clinical consequence was found except for persistent fatigue
      despite anemia correction in some patients. Conclusions. Hypophosphatemia is
      frequent after parenteral FCM injection and may have clinical consequences,
      including persistent fatigue. Further studies of chronic hypophosphatemia long
      term consequences, especially bone assessments, are needed. 

PMID- 26000020
TI  - Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine
      Breast Adenocarcinoma through Different Approaches.
AB  - The use of Mesenchymal Stromal Cells (MSCs) aiming to treat cancer has shown very
      contradictory results. In an attempt to clarify the contradictory results
      reported in the literature and the possible role of human fallopian tube
      Mesenchymal Stromal Cells (htMSCs) against breast cancer, the aim of this study
      was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma
      using two different approaches: (1) coinjections of htMSCs and 4T1 murine tumor
      cell lineage and (2) injections of htMSCs in mice at the initial stage of mammary
      adenocarcinoma development. Coinjected animals had a more severe course of the
      disease and a reduced survival, while tumor-bearing animals treated with 2
      intraperitoneal injections of 10(6) htMSCs showed significantly reduced tumor
      growth and increased lifespan as compared with control animals. Coculture of
      htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased
      VEGF production. For the first time, we show that MSCs isolated from a single
      source and donor when injected in the same animal model and tumor can lead to
      opposite results depending on the experimental protocol. Also, our results
      demonstrated that htMSCs can have an inhibitory effect on the development of
      murine mammary adenocarcinoma. 

PMID- 26000019
TI  - The role of adipose-derived stem cells in breast cancer progression and
      metastasis.
AB  - Conventional breast cancer extirpation involves resection of parts of or the
      whole gland, resulting in asymmetry and disfiguration. Given the unsatisfactory
      aesthetic outcomes, patients often desire postmastectomy reconstructive
      procedures. Autologous fat grafting has been proposed for reconstructive purposes
      for decades to restore form and anatomy after mastectomy. Fat has the inherent
      advantage of being autologous tissue and the most natural-appearing filler, but
      given its inconsistent engraftment and retention rates, it lacks reliability.
      Implementation of autologous fat grafts with cellular adjuncts, such as
      multipotent adipose-derived stem cells (ADSCs), has shown promising results.
      However, it is pertinent and critical to question whether these cells could
      promote any residual tumor cells to proliferate, differentiate, or metastasize or
      even induce de novo carcinogenesis. Thus far, preclinical and clinical study
      findings are discordant. A trend towards potential promotion of both breast
      cancer growth and invasion by ADSCs found in basic science studies was indeed not
      confirmed in clinical trials. Whether experimental findings eventually correlate
      with or will be predictive of clinical outcomes remains unclear. Herein, we aimed
      to concisely review current experimental findings on the interaction of
      mesenchymal stem cells and breast cancer, mainly focusing on ADSCs as a promising
      tool for regenerative medicine, and discuss the implications in clinical
      translation. 

PMID- 26000021
TI  - Endothelial progenitor cells in tumor angiogenesis: another brick in the wall.
AB  - Until 15 years ago, vasculogenesis, the formation of new blood vessels from
      undifferentiated cells, was thought to occur only during embryonic development.
      The discovery of circulating cells that are able to promote vascular regeneration
      and repair-the so-called endothelial progenitor cells (EPCs)-changed that, and
      EPCs have since been studied extensively. It is already known that EPCs include
      many subtypes of cells that play a variety of roles in promoting vascular growth.
      Some EPCs are destined to differentiate into endothelial cells, whereas others
      are capable of promoting and sustaining angiogenesis through paracrine
      mechanisms. Vasculogenesis and angiogenesis might constitute complementary
      mechanisms for postnatal neovascularization, and EPCs could be at the core of
      this process. Although the formation of new blood vessels from preexisting
      vasculature plays a beneficial role in many physiological processes, such as
      wound healing, it also contributes to tumor growth and metastasis. However, many
      aspects of the role played by EPCs in tumor angiogenesis remain unclear. This
      review aims to address the main aspects of EPCs differentiation and certain
      characteristics of their main function, especially in tumor angiogenesis, as well
      as the potential clinical applications. 

PMID- 26000022
TI  - Combined effects of pericytes in the tumor microenvironment.
AB  - Pericytes are multipotent perivascular cells whose involvement in vasculature
      development is well established. Evidences in the literature also suggest that
      pericytes display immune properties and that these cells may serve as an in vivo
      reservoir of stem cells, contributing to the regeneration of diverse tissues.
      Pericytes are also capable of tumor homing and are important cellular components
      of the tumor microenvironment (TME). In this review, we highlight the
      contribution of pericytes to some classical hallmarks of cancer, namely, tumor
      angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss
      how collectively these hallmarks could be tackled by therapies targeting
      pericytes, providing a rationale for cancer drugs aiming at the TME. 

PMID- 26000023
TI  - Determination of heavy metals concentration in traditional herbs commonly
      consumed in the United Arab Emirates.
AB  - Herbs are extensively consumed in the United Arab Emirates for their flavoring
      and medicinal properties. This study aimed at determining the concentration of
      heavy metals in selected traditional herbs consumed in the United Arab Emirates
      (UAE). A total of 81 samples of seven herbs, parsley (Petroselinum crispum),
      basil (Ocimum basilicum), sage (Salvia officinalis), oregano (Origanum vulgare),
      mint (Mentha spicata), thyme (Thymus vulgaris), and chamomile (Matricaria
      chamomilla), were purchased from the local market in Dubai and analyzed for their
      cadmium, lead, copper, iron, and zinc contents. Microwave-assisted digestion was
      applied for the dissolution of the samples and heavy metals concentration was
      determined using Atomic Absorption Spectrometry (AAS). Metals were found to be
      present in varied concentrations in the herb samples. The concentration ranges
      were found as follows: less than 0.1-1.11 mg.kg(-1) for cadmium, less than 1.0
      23.52 mg.kg(-1) for lead, 1.44-156.24 mg.kg(-1) for copper, 12.65-146.67 mg.kg(
      1) for zinc, and 81.25-1101.22 mg.kg(-1) for iron. The findings of the study
      suggest that most of the analyzed herbs contained unsafe levels of heavy metals
      that exceeded the World Health Organization (WHO) permissible limits (PL). 

PMID- 26000025
TI  - Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential
      Oil.
AB  - Eyebright, Euphrasia rostkoviana Hayne (Scrophulariaceae), is a medicinal plant
      traditionally used in Europe for the treatment of various health disorders,
      especially as eyewash to treat eye ailments such as conjunctivitis and
      blepharitis that can be associated with bacterial infections. Some Euphrasia
      species have been previously reported to contain essential oil. However, the
      composition and bioactivity of E. rostkoviana oil are unknown. Therefore, in this
      study, we investigated the chemical composition and antimicrobial activity of the
      eyebright essential oil against some organisms associated with eye infections:
      Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus
      aureus, S. epidermidis, Pseudomonas aeruginosa, and Candida albicans. GC-MS
      analysis revealed more than 70 constituents, with n-hexadecanoic acid (18.47%) as
      the main constituent followed by thymol (7.97%), myristic acid (4.71%), linalool
      (4.65%), and anethole (4.09%). The essential oil showed antimicrobial effect
      against all organisms tested with the exception of P. aeruginosa. The best
      activity was observed against all Gram-positive bacteria tested with the minimum
      inhibitory concentrations of 512 ug/mL. This is the first report on the chemical
      composition of E. rostkoviana essential oil and its antimicrobial activity. 

PMID- 26000024
TI  - The road from next-generation sequencing to personalized medicine.
AB  - Moving from a traditional medical model of treating pathologies to an
      individualized predictive and preventive model of personalized medicine promises
      to reduce the healthcare cost on an overburdened and overwhelmed system. Next
      generation sequencing (NGS) has the potential to accelerate the early detection
      of disorders and the identification of pharmacogenetics markers to customize
      treatments. This review explains the historical facts that led to the development
      of NGS along with the strengths and weakness of NGS, with a special emphasis on
      the analytical aspects used to process NGS data. There are solutions to all the
      steps necessary for performing NGS in the clinical context where the majority of
      them are very efficient, but there are some crucial steps in the process that
      need immediate attention.

PMID- 26000026
TI  - Trigonella foenum-graceum (Seed) Extract Interferes with Quorum Sensing Regulated
      Traits and Biofilm Formation in the Strains of Pseudomonas aeruginosa and
      Aeromonas hydrophila.
AB  - Trigonella foenum-graecum L. (Fenugreek) is an important plant of the Leguminosae
      family known to have medicinal properties. However, fraction based antiquorum
      sensing and antibiofilm activities have not been reported from this plant. In the
      present study T. foenum-graecum seed extract was sequentially fractionated and
      sub-MICs were tested for above activities. The methanol fraction of the extract
      demonstrated significant inhibition of AHL regulated virulence factors: protease,
      LasB elastase, pyocyanin production, chitinase, EPS, and swarming motility in
      Pseudomonas aeruginosa PAO1 and PAF79. Further, QS dependent virulence factor in
      the aquatic pathogen Aeromonas hydrophila WAF38 was also reduced. Application of
      T. foenum-graecum seed extract to PAO1, PAF79, and WAF38 decreased the biofilm
      forming abilities of the pathogens by significant levels. The extract also
      exhibited reduced AHL levels and subsequent downregulation of lasB gene. In vivo
      study showed an enhanced survival of PAO1-preinfected C. elegans after treatment
      with extract at 1 mg/mL. Further, the major compound detected by GC-MS, caffeine,
      reduced the production of QS regulated virulence factors and biofilm at 200 ug/mL
      concentration indicating its role in the activity of the methanol extract. The
      results of the present study reveal the potential anti-QS and antibiofilm
      property of T. foenum-graceum extract and caffeine. 

PMID- 26000027
TI  - The immunomodulatory effect of acupoint application for childhood asthma: a
      systematic review and meta-analysis.
AB  - Objective. To evaluate the evidence on the immunomodulatory effect of acupoint
      application for childhood asthma. Methods. Five electronic databases through
      October 2014 were searched. The risk of bias in eligible studies was assessed
      using the Cochrane Collaboration tool. Standardised mean difference (SMD) and 95%
      confidence intervals (CI) of random-effects model were calculated. And
      heterogeneity was assessed using the Cochran Q statistic and quantified with the
      I (2) index. Results. Six studies were included in our review. The aggregated
      results suggested that acupoint application showed the beneficial effect for
      childhood asthma in improving IgA (SMD, -0.83; 95% CI -1.14 to -0.52; P <
      0.00001), IgE (SMD, -0.52; 95% CI -0.76 to -0.29; P < 0.001), IgG (SMD, -1.17;
      95% CI -1.61 to -0.74; P < 0.0001), IL-4 (SMD, -0.57; 95% CI -0.91 to -0.23; P =
      0.0009), and IFN-gamma (SMD, -0.38; 95% CI -0.71 to -0.04; P = 0.03) but not IgM
      (SMD, -0.40; 95% CI -0.98 to 0.18; P = 0.18). And the effective dose of acupoint
      application may be 2-6 hours/time and a total of 3 times within 4 weeks.
      Conclusions. This review showed the positive evidence that acupoint application
      had the favorable immunomodulatory effect for childhood asthma. However, more
      studies with long follow-up are warrant to confirm the current findings. 

PMID- 26000028
TI  - Disease progression of HIV-1 infection in symptomatic and asymptomatic
      seroconverters in Osaka, Japan: a retrospective observational study.
AB  - BACKGROUND: Estimates of the interval from HIV-1 infection to disease progression
      may be affected by selection bias, and data concerning asymptomatic early
      seroconverters are limited. We examined the interval until disease progression in
      HIV-1 seroconverters in whom the timing of infection could be estimated within 1
      year before diagnosis. METHODS: Subjects included newly diagnosed patients at
      Osaka National Hospital between 2003 and 2010 who had either (1) symptomatic
      acute HIV-1 infection with a negative or intermediate reaction on Western
      blotting and a positive reaction on an HIV RNA test (symptomatic acute group) or
      (2) a positive reaction on Western blotting at diagnosis and a <1-year interval
      from the last negative HIV test until the first positive test. The latter was
      divided into symptomatic recent or asymptomatic recent groups based on the
      presence or absence, respectively, of any transient fever between the last
      negative and first positive tests. Disease progression was defined as a fall in
      the CD4 count to <350 cells/microL on 2 consecutive tests, the start of anti-HIV
      therapy, or the onset of AIDS-indicator diseases. Information was retrospectively
      collected from medical records. RESULTS: Subjects included 210 patients: 91 in
      the symptomatic acute group, 72 in the symptomatic recent group, and 47 in the
      asymptomatic recent group. In the symptomatic acute (0.8 years) and symptomatic
      recent (2.2 years) groups, the Kaplan-Meier estimate of median interval until
      disease progression was significantly shorter than that in the asymptomatic
      recent group (2.9 years). Multivariate analysis by Cox's proportional hazards
      test showed that the symptomatic acute group (vs. asymptomatic recent group:
      hazard ratio: 1.93; 95% confidence interval: 1.14-3.36; p = 0.0140) and a
      baseline CD4 count of <400 cells/microL (hazard ratio: 3.88; 95% confidence
      interval: 2.57-5.96; p < 0.0001) were independent prognostic factors associated
      with early disease progression. CONCLUSIONS: Symptomatic seroconversion was
      associated with early disease progression. Furthermore, the estimated median
      interval until the CD4 count was <350 cells/microL was only 2.9 years even in
      patients with asymptomatic seroconversion. These results suggest the importance
      of early diagnosis in early seroconverters.

PMID- 26000029
TI  - The economic benefits of increasing kangaroo skin-to-skin care and breastfeeding
      in neonatal units: analysis of a pragmatic intervention in clinical practice.
AB  - BACKGROUND: A number of significant recent research studies have used techniques
      of economic modelling to demonstrate the potential benefits of increasing
      breastfeeding rates in the UK overall, and specifically in neonatal care. This
      paper complements this growing body of evidence by presenting an economic
      analysis of data from an actual intervention, the 'Getting It Right From the
      Start' programme, which took place in the north of the UK during 2011-12, with
      the aim of increasing breastfeeding and kangaroo skin-to-skin care rates in
      neonatal units. METHODS: 'Getting It Right from the Start' was a pragmatic,
      multifaceted programme of change delivered under the auspices of the regional
      Health Innovation and Education Cluster, of which 17 were established in the UK
      in 2010. It engaged with 18 neonatal units in two Neonatal Networks with the aim
      of increasing kangaroo skin-to-skin care and breastfeeding rates. As part of the
      evaluation of the programme, we conducted an economic study comparing the overall
      costs and benefits of the intervention. RESULTS: Overall, the economic analysis
      demonstrated that for every L1 invested in the intervention to increase kangaroo
      skin-to-skin care and breastfeeding rates, between L4.00 and L13.82 of benefit
      was generated. This was spread across different healthcare settings and the
      timescale for the realisation of benefits will vary. The increases in kangaroo
      skin-to-skin care generated the greatest cost savings, with potential cost
      savings ranging between L668,000 (minimum cost assumptions) to more than L2 m
      (maximum cost assumptions). Increases in breastfeeding associated with the
      project generated between L68,486 and L582,432. The majority of the cost savings
      generated were associated with reductions in cases of gastroenteritis and
      necrotising enterocolitis. CONCLUSION: This was one of the first economic
      evaluations of an actual intervention to increase breastfeeding and kangaroo skin
      to-skin care in neonatal units. It complements the existing economic models by
      demonstrating that a real intervention in clinical practice was both cost
      effective as well as clinically beneficial. Future interventions with similar
      methodology should be supported and considered likely to generate significant
      cost savings compared to outlay. Economic evaluation should be more frequently
      included in studies of practical interventions in clinical settings to increase
      breastfeeding.

PMID- 26000030
TI  - A mathematical model quantifies proliferation and motility effects of TGF-beta on
      cancer cells.
AB  - Transforming growth factor (TGF)-beta is known to have properties of both a
      tumour suppressor and a tumour promoter. While it inhibits cell proliferation, it
      also increases cell motility and decreases cell-cell adhesion. Coupling
      mathematical modelling and experiments, we investigate the growth and motility of
      oncogene-expressing human mammary epithelial cells under exposure to TGF-beta. We
      use a version of the well-known Fisher-Kolmogorov equation, and prescribe a
      procedure for its parametrisation. We quantify the simultaneous effects of TGF
      beta to increase the tendency of individual cells and cell clusters to move
      randomly and to decrease overall population growth. We demonstrate that in
      experiments with TGF-beta treated cells in vitro, TGF-beta increases cell
      motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in
      comparison with untreated cells.

PMID- 26000031
TI  - "Bone-omicronn-Bone" surgical reconstruction of moderate severity, flexible
      single curve adolescent idiopathic scoliosis: continuing improvements of the
      technique and results in three scoliosis centers after almost twenty years of
      use.
AB  - The "bone-on-bone" reconstruction for adolescent idiopathic scoliosis is reviewed
      in this article. Extensive use over the past 18 years has identified it's
      functional benefits outstanding clinical results, and very limited complications.
      This is an extensive update of it's application, since it's introduction, 18
      years ago. 

PMID- 26000032
TI  - A graph modification approach for finding core-periphery structures in protein
      interaction networks.
AB  - The core-periphery model for protein interaction (PPI) networks assumes that
      protein complexes in these networks consist of a dense core and a possibly sparse
      periphery that is adjacent to vertices in the core of the complex. In this work,
      we aim at uncovering a global core-periphery structure for a given PPI network.
      We propose two exact graph-theoretic formulations for this task, which aim to fit
      the input network to a hypothetical ground truth network by a minimum number of
      edge modifications. In one model each cluster has its own periphery, and in the
      other the periphery is shared. We first analyze both models from a theoretical
      point of view, showing their NP-hardness. Then, we devise efficient exact and
      heuristic algorithms for both models and finally perform an evaluation on
      subnetworks of the S. cerevisiae PPI network. 

PMID- 26000033
TI  - Mechanical properties of beta-HMX.
AB  - BACKGROUND: For a full understanding of the mechanical properties of a material,
      it is essential to understand the defect structures and associated properties and
      microhardness indentation is a technique that can aid this understanding.
      RESULTS: The Vickers hardness on (010), {011} and {110} faces lay in the range of
      304-363 MPa. The Knoop Hardnesses on the same faces lay in the range 314-482 MPa.
      From etching of three indented surfaces, the preferred slip planes have been
      identified as (001) and (101). For a dislocation glide, the most likely
      configuration for dislocation movement on the (001) planes is (001) [100] (|b| =
      0.65 nm) and for the (101) plane as (101) [Formula: see text] (|b| = 1.084 nm)
      although (101) [010] (|b| = 1.105 nm) is possible. Tensile testing showed that at
      a stress value of 2.3 MPa primary twinning occurred and grew with increasing
      stress. When the stress was relaxed, the twins decreased in size, but did not
      disappear. The twinning shear strain was calculated to be 0.353 for the (101)
      twin plane. CONCLUSIONS: HMX is considered to be brittle, compared to other
      secondary explosives. Comparing HMX with a range of organic solids, the values
      for hardness numbers are similar to those of other brittle systems. Under the
      conditions developed beneath a pyramidal indenter, dislocation slip plays a major
      part in accommodating the local deformation stresses. Graphical abstractHMX
      undergoing tensile testing.

PMID- 26000034
TI  - Employing aromatic tuning to modulate output from two-component signaling
      circuits.
AB  - Two-component signaling circuits (TCSs) govern the majority of environmental,
      pathogenic and industrial processes undertaken by bacteria. Therefore,
      controlling signal output from these circuits in a stimulus-independent manner is
      of central importance to synthetic microbiologists. Aromatic tuning, or
      repositioning the aromatic residues commonly found at the cytoplasmic end of the
      final TM helix has been shown to modulate signal output from the aspartate
      chemoreceptor (Tar) and the major osmosensor (EnvZ) of Escherichia coli. Aromatic
      residues are found in a similar location within other bacterial membrane-spanning
      receptors, suggesting that aromatic tuning could be harnessed for a wide-range of
      applications. Here, a brief synopsis of the data underpinning aromatic tuning,
      the initial successes with the method and the inherent advantages over those
      previously employed for modulating TCS signal output are presented. 

PMID- 26000035
TI  - Trends and factors associated with mental health problems among children and
      adolescents in Malaysia.
AB  - Studying trends in mental health morbidity will guide the planning of future
      interventions for mental and public health services. To assess the trends in
      mental health problems among children and adolescents aged 5 through 15 years in
      Malaysia from 1996 to 2011, data from the children's mental health component of
      three population-based surveys was analysed using a two-stage stratified sampling
      design. Mental health problems were assessed using the Reporting Questionnaire
      for Children. The prevalence of mental health problems among children and
      adolescents aged 5 through 15 years showed an increasing trend from 13.0% (95%
      Confidence Interval [CI]: 11.5-14.6) in 1996 to 19.4% (95% CI: 18.5-20.3) in 2006
      and 20.0% (95% CI: 18.8-21.3) in 2011. In 2011, male children and adolescents and
      those who were in less affluent families were significantly associated with
      mental health problems. The findings indicate that even though mental health
      problems among children and adolescents in Malaysia are increasing, the rate of
      increase has decreased in the past five years. Socially and economically
      disadvantaged groups were most vulnerable to mental health problems.

PMID- 26000036
TI  - Contribution of a family 1 carbohydrate-binding module in thermostable glycoside
      hydrolase 10 xylanase from Talaromyces cellulolyticus toward synergistic
      enzymatic hydrolysis of lignocellulose.
AB  - BACKGROUND: Enzymatic removal of hemicellulose components such as xylan is an
      important factor for maintaining high glucose conversion from lignocelluloses
      subjected to low-severity pretreatment. Supplementation of xylanase in the
      cellulase mixture enhances glucose release from pretreated lignocellulose.
      Filamentous fungi produce multiple xylanases in their cellulase system, and some
      of them have modular structures consisting of a catalytic domain and a family 1
      carbohydrate-binding module (CBM1). However, the role of CBM1 in xylanase in the
      synergistic hydrolysis of lignocellulose has not been investigated in depth.
      RESULTS: Thermostable endo-beta-1,4-xylanase (Xyl10A) from Talaromyces
      cellulolyticus, which is recognized as one of the core enzymes in the fungal
      cellulase system, has a modular structure consisting of a glycoside hydrolase
      family 10 catalytic domain and CBM1 at the C-terminus separated by a linker
      region. Three recombinant Xyl10A variants, that is, intact Xyl10A (Xyl10Awt),
      CBM1-deleted Xyl10A (Xyl10AdC), and CBM1 and linker region-deleted Xyl10A
      (Xyl10AdLC), were constructed and overexpressed in T. cellulolyticus. Cellulose
      binding ability of Xyl10A CBM1 was demonstrated using quartz crystal microbalance
      with dissipation monitoring. Xyl10AdC and Xyl10AdLC showed relatively high
      catalytic activities for soluble and insoluble xylan substrates, whereas Xyl10Awt
      was more effective in xylan hydrolysis of wet disc-mill treated rice straw (WDM
      RS). The enzyme mixture of cellulase monocomponents and intact or mutant Xyl10A
      enhanced the hydrolysis of WDM-RS glucan, with the most efficient synergism found
      in the interactions with Xyl10Awt. The increased glucan hydrolysis yield
      exhibited a linear relationship with the xylan hydrolysis yield by each enzyme.
      This relationship revealed significant hydrolysis of WDM-RS glucan with lower
      supplementation of Xyl10Awt. CONCLUSIONS: Our results suggest that Xyl10A CBM1
      has the following two roles in synergistic hydrolysis of lignocellulose by Xyl10A
      and cellulases: enhancement of lignocellulosic xylan hydrolysis by binding to
      cellulose, and the efficient removal of xylan obstacles that interrupt the
      cellulase activity (because of similar binding target of CBM1). The combination
      of CBM-containing cellulases and xylanases in a fugal cellulase system could
      contribute to reduction of the enzyme loading in the hydrolysis of pretreated
      lignocelluloses.

PMID- 26000038
TI  - Effects of 1-year yoga on cardiovascular risk factors in middle-aged and older
      adults with metabolic syndrome: a randomized trial.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a clustering of cardiovascular risk
      factors, which is associated with diabetes mellitus and cardiovascular disease.
      Lifestyle interventions applied to people with MetS has considerable beneficial
      effects on disease preventive outcomes. This study aimed to examine the effects
      of 1-year of yoga exercise on the cardiovascular risk factors including central
      obesity, hypertension, dyslipidemia and hyperglycemia in middle-aged and older
      Hong Kong Chinese adults with MetS. METHODS: Adults diagnosed with MetS using
      National Cholesterol Education Program criteria (n = 182; mean +/- SD age = 56 +/
      9.1) were randomly assigned to a 1-year yoga intervention group or control
      group. Systolic and diastolic blood pressure, waist circumference, fasting plasma
      glucose, triglycerides, and high-density lipoprotein cholesterol were examined at
      baseline, midway, and on completion of the study. Physical activity level and
      caloric intake were assessed and included in the covariate analyses. RESULTS: A
      reduction of the number of diagnostic components for MetS was found to be
      associated with the yoga intervention. Waist circumference was significantly
      improved after the 1-year yoga intervention. A trend towards a decrease in
      systolic blood pressure was observed following yoga intervention. CONCLUSION:
      These results suggest that yoga exercise improves the cardiovascular risk factors
      including central obesity and blood pressure in middle-aged and older adults with
      MetS. These findings support the complementary beneficial role of yoga in
      managing MetS.

PMID- 26000037
TI  - Second degree AV block and severely impaired contractility in cardiac myxedema: a
      case report.
AB  - The heart is a major target organ for thyroid hormone action. Severe overt
      hypothyroidism can result in diastolic hypertension, lowered cardiac output,
      impaired left ventricular contractility and diastolic relaxation, pericardial
      effusion and bradycardia. However, the function of the atrial pacemaker is
      usually normal and the degree by which the heart rate slows down is often modest.
      Here we report the case of a 20 year old male Caucasian with severe overt
      hypothyroidism. He presented with syncopation due to second degree
      atrioventricular block type Mobitz 2 and heart failure with reduced ejection
      fraction (38 %). Laboratory testing revealed a severe overt hypothyroidism with
      markedly elevated TSH (>100 mIU/L) and reduced fT3 and fT4 levels. The condition
      was caused by hypothyroid Graves' disease (Graves' disease with Hashimoto
      component). Although magnetic resonance imaging of the heart demonstrated
      decreased cardiac contractility and pericardial effusion, suggesting peri
      myocarditis, plasma levels for BNP and troponin I were low. A possible infectious
      cause was unlikely, since testing for cardiotropic viruses was negative. The
      patient was treated with intravenous levothyroxine and after peripheral
      euthyroidism had been achieved, left ventricular ejection fraction returned to
      normal and pericardial effusion dissolved. Additionally, bradycardiac episodes
      abated, although intermittent second degree AV block was still occasionally
      present during the night. In conclusion, overt hypothyroidism may be associated
      by cardiac myxedema affecting both electrophysiology and contractility,
      observations that underscore the necessity of thyroid testing in different
      phenotypes of heart failure. 

PMID- 26000040
TI  - Significant prognostic impact of chemoradiotherapy-induced hemoglobin decrease on
      treatment outcomes of nasopharyngeal carcinoma.
AB  - PURPOSE: To investigate prognostic impact of chemoradiotherapy-induced hemoglobin
      (Hb) decrease on treatment outcomes of endemic nasopharyngeal carcinoma (NPC).
      MATERIALS AND METHODS: Eight hundred and fifteen non-metastatic NPC, receiving
      neoadjuvant chemotherapy followed by radiotherapy (NACT+RT group) or concomitant
      chemoradiotherapy (CCRT group), were enrolled in this study, who were regrouped
      according to pre-radiotherapy Hb (pre-RT Hb), post-radiotherapy Hb (post-RT Hb)
      and individual Hb decrease through radiotherapy or CCRT (?Hb), respectively.
      Survival curves were estimated using Kaplan-Meier method and compared by log-rank
      test. Multivariate analysis was performed using the COX proportional hazard model
      and binary logistic regression model. RESULTS: A poorer 5-year disease-free
      survival (DFS) was observed when pre-RT Hb<130.00 g/L. However, post-RT Hb<130.00
      g/L was associated with significantly poorer 5-year locoregional recurrence-free
      survival (LRFS) (P=0.010) and disease specific survival (DSS) (P=0.008).
      Multivariate analysis with the COX proportional hazard model identified post-RT
      Hb<130.00 g/L as an independent negative prognostic factor for both LRFS (hazard
      ratio [HR], 1.896; 95% confidence interval [CI], 1.158-3.106; P=0.011) and DSS
      (HR, 1.767; 95% CI, 1.152-2.711; P=0.009). Similarly, ?Hb <-15.00 g/L also
      predicted poorer 5-year LRFS (P=0.024) and DSS (P=0.015), which was confirmed in
      multivariate analysis as an independent adverse prognostic factor for LRFS (HR,
      1.586; 95% CI, 1.058-2.377; P=0.026) and DSS (HR, 1.556; 95% CI, 1.087-2.227;
      P=0.016), respectively. Multivariate analysis with binary logistic regression
      model indicated that CCRT was a significantly independent predictor for post-RT
      Hb <130.00 g/L and ?Hb < -15.00 g/L. CONCLUSIONS: Chemoradiotherapy-induced
      decreased Hb levels have negative influence on locoregional control and survival,
      and might counteract the benefit of neoadjuvant/concomitant chemotherapy. Further
      studies on supportive care to maintain sufficient Hb level during chemo
      radiotherapy are warranted.

PMID- 26000039
TI  - Reconstitution of the ERG Gene Expression Network Reveals New Biomarkers and
      Therapeutic Targets in ERG Positive Prostate Tumors.
AB  - BACKGROUND: Despite a growing number of studies evaluating cancer of prostate
      (CaP) specific gene alterations, oncogenic activation of the ETS Related Gene
      (ERG) by gene fusions remains the most validated cancer gene alteration in CaP.
      Prevalent gene fusions have been described between the ERG gene and promoter
      upstream sequences of androgen-inducible genes, predominantly TMPRSS2
      (transmembrane protease serine 2). Despite the extensive evaluations of ERG
      genomic rearrangements, fusion transcripts and the ERG oncoprotein, the
      prognostic value of ERG remains to be better understood. Using gene expression
      dataset from matched prostate tumor and normal epithelial cells from an 80
      GeneChip experiment examining 40 tumors and their matching normal pairs in 40
      patients with known ERG status, we conducted a cancer signaling-focused
      functional analysis of prostatic carcinoma representing moderate and aggressive
      cancers stratified by ERG expression. RESULTS: In the present study of matched
      pairs of laser capture microdissected normal epithelial cells and well-to
      moderately differentiated tumor epithelial cells with known ERG gene expression
      status from 20 patients with localized prostate cancer, we have discovered novel
      ERG associated biochemical networks. CONCLUSIONS: Using causal network
      reconstruction methods, we have identified three major signaling pathways related
      to MAPK/PI3K cascade that may indeed contribute synergistically to the ERG
      dependent tumor development. Moreover, the key components of these pathways have
      potential as biomarkers and therapeutic target for ERG positive prostate tumors.

PMID- 26000041
TI  - TGF-beta Induces Degradation of PTHrP Through Ubiquitin-Proteasome System in
      Hepatocellular Carcinoma.
AB  - Both transforming growth factor-beta (TGF-beta) and parathyroid hormone-related
      protein (PTHrP) regulate important cellular processes, such as apoptosis in the
      development of hepatocellular carcinoma. However, the mechanisms of regulation of
      PTHrP by TGF-beta are largely unknown. We hypothesized that TGF-beta regulates
      the expression of PTHrP protein through a post-translational mechanism. Using
      hepatocellular carcinoma cell lines as the in vitro model, we investigated the
      effects of TGF-beta on protein expression and post-translational processing of
      PTHrP. We found that TGF-beta treatment led to protein degradation of PTHrP
      through the ubiquitin-proteasome-dependent pathway. We also provided evidence to
      show that Smurf2 was the E3 ligase responsible for the ubiquitination of PTHrP.
      Furthermore, using immunohistochemistry on human hepatocellular carcinoma
      specimens and a tissue array, we found that the expression of PTHrP was
      predominantly in the cancer cells, whereas the expression of TGF-beta was present
      in non-neoplastic liver tissue adjacent to hepatocellular carcinoma. Our findings
      reveal a novel mechanism whereby TGF-beta may regulate PTHrP in hepatocellular
      carcinogenesis and lack of TGF-beta in hepatocellular carcinoma may promote
      cancer progression. Promotion of PTHrP degradation provides a novel target of
      therapeutic intervention to sensitize hepatocellular carcinoma cells to
      cytostatic and/or pro-apoptotic signals. 

PMID- 26000042
TI  - High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1
      CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C.
AB  - 48 different Pearson mutual-positive-correlation epidermal growth factor receptor
      (EGFR_1)-activatory molecular feedback, up- and down-stream network was
      constructed from 171 overlapping of 366 GRNInfer and 223 Pearson under EGFR_1 CC
      >=0.25 in high lung adenocarcinoma compared with low human normal adjacent
      tissues. Our identified EGFR_1 inside-out upstream activated molecular network
      showed SLC2A1 (solute carrier family 2 (facilitated glucose transporter) member
      1), CCNB2 (cyclin B2), HMMR (hyaluronan-mediated motility receptor (RHAMM)),
      KIF11 (kinesin family member 11), NUSAP1 (nucleolar and spindle associated
      protein 1), PRC1 (protein regulator of cytokinesis 1), UBE2C (ubiquitin
      conjugating enzyme E2C) in high lung adenocarcinoma. EGFR_1 inside-out upstream
      activated terms network includes intracellular, membrane fraction, cytoplasm,
      plasma membrane, integral to membrane, basolateral plasma membrane, transmembrane
      transport, nucleus, cytosol, cell surface; T cell homeostasis, inflammation;
      microtubule cytoskeleton, embryonic development (sensu Mammalia), cell cycle,
      mitosis, thymus development, cell division, regulation of cell cycle, Contributed
      -cellular process--Hs cell cycle KEGG, cytokinesis, M phase, M phase of mitotic
      cell cycle, estrogen-responsive protein Efp controls cell cycle and breast tumors
      growth, cell motility, locomotion, locomotory behavior, neoplasm metastasis,
      spindle pole, spindle microtubule, microtubule motor activity, microtubule-based
      movement, mitotic spindle organization and biogenesis, mitotic centrosome
      separation, spindle pole body organization and biogenesis, microtubule-based
      process, microtubule, cytokinesis after mitosis, mitotic chromosome condensation,
      establishment of mitotic spindle localization, positive regulation of mitosis,
      mitotic spindle elongation, spindle organization and biogenesis, positive
      regulation of exit from mitosis, regulation of cell proliferation, positive
      regulation of cell proliferation based on integrative GO, KEGG, GenMAPP, BioCarta
      and disease databases in high lung adenocarcinoma. Therefore, we propose high
      EGFR_1 inside-out activated inflammation-induced motility through SLC2A1-CCNB2
      HMMR-KIF11-NUSAP1-PRC1-UBE2C in lung adenocarcinoma. 

PMID- 26000043
TI  - Complement receptor 1 genetic variants contribute to the susceptibility to
      gastric cancer in chinese population.
AB  - As the receptor for C3b/C4b, type 1 complement receptor (CR1/CD35) plays an
      important role in the regulation of complement activity and is further involved
      in carcinogenesis. This study aimed to elucidate the association of CR1 genetic
      variants with the susceptibility to gastric cancer in Chinese population. Based
      on the NCBI database, totally 13 tag single nucleotide polymorphisms (SNPs) were
      selected by Haploview program and genotyped using iPlex Gold Genotyping Assay and
      Sequenom MassArray among 500 gastric cancer cases and 500 healthy controls. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic
      regression to evaluate the association of each SNP with gastric cancer. Of all
      selected Tag SNPs , CR1 rs9429942 T > C was found to confer to the risk of
      developing gastric cancer. Compared with the carriers with rs9429942 TT genotype,
      those with CT genotype had 88% decreased risk of developing gastric cancer with
      OR (95%CI) of 0.12 (0.03-0.50). Generalized multifactor dimensionality reduction
      (GMDR) analysis revealed a significant three-way interaction among rs75422544 C >
      A, rs10494885 C > T and rs7525160 G > C in the development of gastric cancer with
      a maximum testing balance accuracy of 56.07% and a cross-validation consistency
      of 7/10 (P = 0.011). In conclusion, our findings demonstrated the genetic role of
      CR1 gene in the development of gastric cancer in Chinese population. 

PMID- 26000044
TI  - Longitudinal FDG-PET Revealed Regional Functional Heterogeneity of Bone Marrow,
      Site-Dependent Response to Treatment and Correlation with Hematological
      Parameters.
AB  - PURPOSE: The purposes of this study were: 1) to show bone marrow (BM) functional
      heterogeneity, 2) to demonstrate site-dependent responses of BM to cancer
      treatment utilizing whole body FDG-PET/CT and 3) to identify correlations between
      FDG uptake in different bone sites and long term complete blood count (CBC).
      METHODS: Thirty two patients who had pre- and post-treatment FDG-PET/CT scans
      were selected retrospectively. Each patient received either head and neck
      radiation for cancer of the tongue, or pelvic radiation for rectal or cervical
      cancer with chemotherapy. Patients had FDG-PET/CT performed prior to the first
      radiation therapy session and at least one FDG-PET/CT after completion of the
      prescribed radiation therapy. RESULTS: FDG uptake before radiotherapy was
      significantly different among bone regions (p < 0.01). This heterogeneity was
      felt to reflect site-dependent amounts of BM contents possibly due to structural
      and functional requirements. FDG uptake in the irradiated regions was
      significantly decreased on the first and second follow-ups after radiation.
      Feasibly, this could be due to a reduction in the number of active BM cells
      following intensive radiation in addition to concurrent chemotherapy. Overall,
      CBC significantly decreased after treatment. Correlation values of each
      hematological parameter with FDG uptake varied among skeletal regions and scan
      time points. FDG uptake in sacrum and lumbar regions had better correlation with
      white blood cells and neutrophils. CONCLUSIONS: Longitudinal FDG-PET revealed a
      regional functional heterogeneity of the BM site-dependent response to treatment.
      Patients experienced immediate and prolonged marrow metabolic damage that
      correlates with hematological parameters. FDG-PET/CT may provide additional
      capabilities to assess BM health.

PMID- 26000045
TI  - Mutual Regulation of FOXM1, NPM and ARF Proteins.
AB  - ARF, NPM and FOXM1 proteins interact with each other in mammalian cells. We
      showed previously that proteasome inhibitors suppress not only FOXM1 expression,
      but also the expression of ARF and NPM proteins. Using RNA interference we found
      that the depletion of each of these proteins by RNAi in human cancer HeLa cells
      leads to down-regulation of the two other partners, suggesting that these
      proteins stabilize each other in human cancer cells. Since the suppression of
      FOXM1 is one of hallmarks of proteasome inhibition, suppression of ARF and NPM by
      proteasome inhibitors may be explained in part as a secondary effect of
      downregulation of FOXM1 that modulate stability of ARF and NPM1 proteins. 

PMID- 26000046
TI  - Overexpression of CUEDC2 Predicts Poor Prognosis in Ovarian Serous Carcinomas.
AB  - CUEDC2, a newly reported protein, plays critical roles in many biological
      processes, such as cell cycle, inflammation and tumorigenesis, however, its
      expression in ovarian serious carcinoma is still poorly understood. In this
      study, we performed an immunohistochemical study on 101 cases of ovarian serous
      carcinoma tissues to investigate whether CUEDC2 is a useful biomarker to evaluate
      the progression of ovarian serous carcinomas. The data showed that the
      overexpression of CUEDC2 was observed in 59.4% of ovarian serous carcinoma tissue
      samples and correlated with histopathological grade, patient age at diagnosis,
      FIGO stage and recurrence. To assess the clinical relevance of CUEDC2, we
      analyzed the survival follow-up information, the results showed that CUEDC2
      positive expression was associated with a shorter disease-free survival time, the
      median disease-free survival time of CUEDC2-positive patients was 36.0 months
      compared with 53.9 months of CUEDC2-negative ones (Log-rank chi(2)=6.149,
      P=0.013). Collectively, our results suggested that CUEDC2 may be a promising
      biomarker to evaluate the progression of serous ovarian carcinoma and to predict
      likely relapse of ovarian serous carcinoma. 

PMID- 26000047
TI  - Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA),
      Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active
      Women.
AB  - INTRODUCTION: Little is known about how modifiable lifestyle factors interact
      with the epigenome to influence disease. Body mass index (BMI, weight kg/height
      m2) and physical activity are associated with postmenopausal breast cancer, but
      the mechanisms are not well-understood. We hypothesized that BMI or physical
      activity may modify the association between markers of global DNA methylation and
      postmenopausal breast cancer risk. METHODS: Resources from a population-based
      case-control study (~1300 postmenopausal women) were used to construct logistic
      regression models. We explored whether the association between breast cancer and
      global methylation, assessed using the luminometric methylation assay (LUMA) and
      long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was
      modified by BMI or recreational physical activity (RPA). RESULTS: The LUMA-breast
      cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004).
      Non-obese women in the highest quartile of LUMA experienced a greater than two
      fold increased risk of postmenopausal breast cancer (BMI<25kg/m2: OR=2.16; 95%
      CI=1.35, 3.57 and BMI 25-29.9kg/m2: OR=2.96; 95% CI=1.69, 5.19) compared to women
      in the lowest LUMA quartile. Similar increases in the LUMA-breast cancer
      association were observed among women who were physically active (moderate RPA:
      OR=2.62; 95% CI=1.44, 4.75 and high RPA: OR=2.62; 95% CI=1.53, 4.49). Estimates
      among obese and inactive women were less pronounced and imprecise. Although we
      observed statistical interactions (p<0.05) between BMI and RPA with LINE-1, we
      were unable to discern any clear associations with breast cancer. CONCLUSIONS:
      The association between LUMA and postmenopausal breast cancer risk may be
      modified by postmenopausal body size and physical activity.

PMID- 26000049
TI  - Defining the role of tyrosine kinase inhibitors in early stage non-small cell
      lung cancer.
AB  - Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity
      and the chemotherapy to the metastatic cancer had limited results. Recent studies
      for the metastatic non-small cell lung cancer led to the ascertainment that the
      NSCLC does not constitute exclusively a disease entity, but different neoplasms
      guided from different molecular paths, different biological behavior and at
      extension requires different confrontation. Thus the new direction for the
      therapeutic approach of NSCLC is henceforth the most individualized approach
      based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are
      driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations,
      and these genetic alterations are sensitized to the inhibition of specific
      oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in
      patients with EGFR mutations it was confirmed by six randomized studies of phase
      III that investigated the role of gefitinib, erlotinib and afatinib. In these
      studies the response rates vary in the impressive percentages from 55% to 86% and
      were connected with a remarkable median progression free survival of
      approximately 8 to 13 months, and with better quality of life compared to that of
      chemotherapy. In early stages NSCLC is needed the individualization of systemic
      treatment in order to reduce toxicity that is observed in the classic
      chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in
      the adjuvant chemotherapy in early stage resected NSCLC. The data from these
      studies suggest that adjuvant TKI therapy might not increase the overall
      survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK
      driven NSCLC subsets potentially offering the opportunity for a definitive answer
      in early disease adjuvant setting (ALCHEMIST) or as induction treatment before
      stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing
      prospective trials may offer the opportunity for a definitive answer of the role
      of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or
      in early disease adjuvant therapy. 

PMID- 26000048
TI  - Hypothesis: Artifacts, Including Spurious Chimeric RNAs with a Short Homologous
      Sequence, Caused by Consecutive Reverse Transcriptions and Endogenous Random
      Primers.
AB  - Recent RNA-sequencing technology and associated bioinformatics have led to
      identification of tens of thousands of putative human chimeric RNAs, i.e. RNAs
      containing sequences from two different genes, most of which are derived from
      neighboring genes on the same chromosome. In this essay, we redefine "two
      neighboring genes" as those producing individual transcripts, and point out two
      known mechanisms for chimeric RNA formation, i.e. transcription from a fusion
      gene or trans-splicing of two RNAs. By our definition, most putative RNA chimeras
      derived from canonically-defined neighboring genes may either be technical
      artifacts or be cis-splicing products of 5'- or 3'-extended RNA of either partner
      that is redefined herein as an unannotated gene, whereas trans-splicing events
      are rare in human cells. Therefore, most authentic chimeric RNAs result from
      fusion genes, about 1,000 of which have been identified hitherto. We propose a
      hypothesis of "consecutive reverse transcriptions (RTs)", i.e. another RT
      reaction following the previous one, for how most spurious chimeric RNAs,
      especially those containing a short homologous sequence, may be generated during
      RT, especially in RNA-sequencing wherein RNAs are fragmented. We also point out
      that RNA samples contain numerous RNA and DNA shreds that can serve as endogenous
      random primers for RT and ensuing polymerase chain reactions (PCR), creating
      artifacts in RT-PCR. 

PMID- 26000050
TI  - Effect of targeted agents on the endocrine response of breast cancer in the
      neoadjuvant setting: a systematic review.
AB  - Inhibition of aberrantly activated pathways cross-talking with hormone receptor
      (HR) improves response to endocrine therapy in patients with HR-positive advanced
      breast cancer. We performed a Pubmed database systematic review to ascertain the
      existence of a better clinical response when combining endocrine therapy with
      targeted agents in the neoadjuvant setting. Preclinical studies or trials
      evaluating toxicity were excluded. We found nine phase II trials that fulfilled
      the research criteria. The endocrine agents used were third generation aromatase
      inhibitors (AIs), anastrozole, letrozole or exemestane. The investigated targeted
      agents were inhibitors of tyrosine kinase receptors such as gefitinib, imatinib
      or trastuzumab/lapatinib, inhibitors of mTOR, such as everolimus, inhibitors of
      COX-2, such as celecoxib, and inhibitors of angiogenesis, such as bevacizumab.
      The response rate (RR) observed combining endocrine and targeted agents ranged
      between 36% and 90%. Overall the studies failed to show a remarkable advantage in
      RR in the combination group compared to historical control subjects receiving AIs
      alone. 

PMID- 26000051
TI  - In Vitro Administration of Gold Nanoparticles Functionalized with MUC-1 Protein
      Fragment Generates Anticancer Vaccine Response via Macrophage Activation and
      Polarization Mechanism.
AB  - Therapeutic cancer vaccines (or active immunotherapy) aim to guide the patient's
      personal immune system to eradicate cancer cells. An exciting approach to cancer
      vaccines has been offered by nanoscale drug delivery systems containing tumor
      associated antigens (TAAs). Their capacity to stimulate the immune system has
      been suggested during late years. However, the role of the macrophages as key
      elements in antigen-presentation process following TAAs-containing nanosystems is
      not completely understood. We aimed to evaluate the effect of gold nanoparticles
      functionalized with mucin-1 peptide (MUC-1) on murine peritoneal macrophages.
      Gold nanoparticles, obtained using a modified Turkevich method, were
      functionalized with MUC-1 protein using Clealand's reagent. The obtained GNP-MUC
      1 solution was used to treat at various concentrations monolayers of peritoneum
      derived macrophages that were further analyzed using confocal and hyperspectral
      microscopy, ELISA assays and spectroscopic techniques. The GNP-MUC-1 nano
      construct had proven to function as a powerful macrophage activator with
      consequent release of cytokines such as: TNF-alpha, IL-6, IL-10 and IL-12 on
      peritoneal macrophages we have isolated from mice. Our results demonstrate
      optimization of antigen-presenting process and predominant M1 polarization
      following exposure GNP-MUC-1. To our best knowledge this is the first study to
      evaluate the anticancer effects of a newly designed nano-biocompound on the
      complex antigen- processing apparatus of peritoneal macrophages. 

PMID- 26000052
TI  - A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging.
AB  - Tumor-associated proteases (TAPs) have been intensively studied because of their
      critical roles in cancer development. As a case in point, expression of matrix
      metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion,
      and metastasis among a majority of cancers. Here we present a prodrug-type, MMP-2
      responsive nanoprobe system with high efficiency and low toxicity for detecting
      MMP-2-overexpressed tumors. The nanoprobe system is featured by its self
      assembled fabrication and FRET effect. This prodrug-type nanoprobe is selectively
      activated by MMP-2, and thus useful for detection of the MMP-2-overexpressed
      cells and tumors. The nanoprobe system works successfully in various animal tumor
      models, including human fibrosarcoma and subcutaneous glioma xenograft.
      Furthermore, in order to overcome the blood brain barrier (BBB) and achieve brain
      tumor targeting, a transferrin-receptor targeting peptide (T7 peptide) is
      strategically incorporated into the nanoprobe. The T7-functionalized nanoprobe is
      capable of detecting the orthotopic brain tumor, with clear, real-time in vivo
      imaging. This method is promising for in vivo detection of brain tumor, and real
      time monitor of a TAP (i.e., MMP-2). 

PMID- 26000053
TI  - On chip analysis of CNS lymphoma in cerebrospinal fluid.
AB  - Molecular profiling of central nervous system lymphomas in cerebrospinal fluid
      (CSF) samples can be challenging due to the paucicellular and limited nature of
      the samples. Presented herein is a microfluidic platform for complete CSF
      lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and
      molecular and chemotherapeutic response profiling via on-chip imaging, all in
      less than one hour. The system can detect scant lymphoma cells and quantitate
      their kappa/lambda immunoglobulin light chain restriction patterns. The approach
      can be further customized for measurement of additional biomarkers, such as those
      for differential diagnosis of lymphoma subtypes or for prognosis, as well as for
      imaging exposure to experimental drugs. 

PMID- 26000054
TI  - Bioluminescence-activated deep-tissue photodynamic therapy of cancer.
AB  - Optical energy can trigger a variety of photochemical processes useful for
      therapies. Owing to the shallow penetration of light in tissues, however, the
      clinical applications of light-activated therapies have been limited.
      Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing
      photochemical activation. Here, we show that efficient bioluminescence energy
      induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep
      tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET
      energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light
      irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence
      agents via draining lymphatic vessels killed tumor cells spread to the sentinel
      and secondary lymph nodes, reduced distant metastases in the lung and improved
      animal survival. Our results show the promising potential of novel
      bioluminescence-activated PDT. 

PMID- 26000055
TI  - A Light-Driven Therapy of Pancreatic Adenocarcinoma Using Gold Nanorods-Based
      Nanocarriers for Co-Delivery of Doxorubicin and siRNA.
AB  - In this work, we report the engineering of polyelectrolyte polymers coated Gold
      nanorods (AuNRs)-based nanocarriers that are capable of co-delivering small
      interfering RNA (siRNA) and an anticancer drug doxorubicin (DOX) to Panc-1 cancer
      cells for combination of both chemo- and siRNA-mediated mutant K-Ras gene
      silencing therapy. Superior anticancer efficacy was observed through synergistic
      combination of promoted siRNA and DOX release upon irradiating the nanoplex
      formulation with 665 nm light. Our antitumor study shows that the synergistic
      effect of AuNRs nanoplex formulation with 665 nm light treatment is able to
      inhibit the in vivo tumor volume growth rate by 90%. The antitumor effect is
      contributed from the inactivation of K-Ras gene and thereby causing a profound
      synthesis (S) phase arrest in treated Panc-1 cells. Our study shows that the
      percentage of Panc-1 cells treated by nanoplex formulation with S phase is
      determined to be 35% and it is 17% much higher than that of Panc-1 cells without
      any treatments. The developed nanotherapy formulation here, that combines
      chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen
      to be the next natural step to be taken in the clinical research for improving
      the therapeutic outcomes of the pancreatic adenocarcinoma treatment. 

PMID- 26000056
TI  - A Two-Step Pretargeted Nanotherapy for CD20 Crosslinking May Achieve Superior
      Anti-Lymphoma Efficacy to Rituximab.
AB  - The use of rituximab, an anti-CD20 mAb, in combination with chemotherapy is the
      current standard for the treatment of B-cell lymphomas. However, because of a
      significant number of treatment failures, there is a demand for new, improved
      therapeutics. Here, we designed a nanomedicine that crosslinks CD20 and directly
      induces apoptosis of B-cells without the need for toxins or immune effector
      functions. The therapeutic system comprises a pretargeting component (anti-CD20
      Fab' conjugated with an oligonucleotide1) and a crosslinking component (N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple complementary
      oligonucleotide2). Consecutive treatment with the two components resulted in CD20
      clustering on the cell surface and effectively killed malignant B-cells in vivo.
      To enhance therapeutic efficacy, a two-step pretargeting approach was employed.
      We showed that the time lag between the two doses can be optimized based on
      pharmacokinetics and biodistribution of the Fab'-oligonucleotide1 conjugate. In a
      mouse model of human non-Hodgkin lymphoma (NHL), increasing the time lag from 1 h
      to 5 h resulted in dramatically improved tumor growth inhibition and animal
      survival. When the 5 h interval was used, the nanotherapy was more efficacious
      than rituximab and led to complete eradication of lymphoma cells with no signs of
      metastasis or disease recurrence. We further evaluated the nanomedicine using
      patient mantle cell lymphoma cells; the treatment demonstrated more potent
      apoptosis-inducing activity than rituximab hyper-crosslinked with secondary
      antibodies. In summary, our approach may constitute a novel treatment for NHL and
      other B-cell malignancies with significant advantages over conventional chemo
      immunotherapy. 

PMID- 26000057
TI  - Photodynamic quenched cathepsin activity based probes for cancer detection and
      macrophage targeted therapy.
AB  - Elevated cathepsins levels and activities are found in several types of human
      cancer, making them valuable biomarkers for detection and targeting therapeutics.
      We designed small molecule quenched activity-based probes (qABPs) that fluoresce
      upon activity-dependent covalent modification, yielding cell killing by
      Photodynamic Therapy (PDT). These novel molecules are highly selective
      theranostic probes that enable both detection and treatment of cancer with
      minimal side effects. Our qABPs carry a photosensitizer (PS), which is activated
      by light, resulting in oxidative stress and subsequent cell ablation, and a
      quencher that when removed by active cathepsins allow the PS to fluoresce and
      demonstrate PD properties. Our most powerful and stable PS-qABP, YBN14, consists
      of a selective cathepsin recognition sequence, a QC-1 quencher and a new
      bacteriochlorin derivative as a PS. YBN14 allowed rapid and selective non
      invasive in vivo imaging of subcutaneous tumors and induced specific tumor
      macrophage apoptosis by light treatment, resulting in a substantial tumor
      shrinkage in an aggressive breast cancer mouse model. These results demonstrate
      for the first time that the PS-qABPs technology offers a functional theranostic
      tool, which can be applied to numerous tumor types and other inflammation
      associated diseases. 

PMID- 26000059
TI  - Prospective Study of (68)Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers
      and First Application in Glioma Patients.
AB  - PURPOSE: The chemokine receptor CXCR4 is overexpressed in various types of human
      cancers. As a specific imaging agent of CXCR4, (68)Ga-NOTA-NFB was investigated
      in this study to assess its safety, biodistribution and dosimetry properties in
      healthy volunteers, and to preliminarily evaluate its application in glioma
      patients. METHODS: Six healthy volunteers underwent whole-body PET scans at 0,
      0.5, 1, 2 and 3 h after (68)Ga-NOTA-NFB injection (mean dose, 182.4 +/- 3.7 MBq
      (4.93 +/- 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples
      were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the
      injection. The estimated radiation doses were calculated by OLINDA/EXM software.
      Eight patients with glioma were enrolled and underwent both (68)Ga-NOTA-NFB and
      (18)F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected
      brain tumor tissues was determined by immunohistochemical staining. RESULTS:
      (68)Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity
      clearance from the blood circulation was observed. The organs with the highest
      absorbed doses were spleen (193.8 +/- 32.5 MUSv/MBq) and liver (119.3 +/- 25.0
      MUSv/MBq). The mean effective dose was 25.4 +/- 6.1 MUSv/MBq. The maximum
      standardized uptake values (SUVmax) and the maximum target to non-target ratios
      (T/NTmax) of (68)Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 +/- 2.90 (range,
      0.45-8.21) and 9.21 +/- 8.75 (range, 3.66-24.88), respectively, while those of
      (18)F-FDG PET/CT were 7.34 +/- 2.90 (range, 3.50-12.27) and 0.86 +/- 0.41 (range,
      0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed
      on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake. CONCLUSION: With
      a favorable radiation dosimetry profile, (68)Ga-NOTA-NFB is safe for clinical
      imaging. Compared to (18)F-FDG PET/CT, (68)Ga-NOTA-NFB PET/CT is more sensitive
      in detecting glioma and could have potential in diagnosing and treatment planning
      for CXCR4 positive patients.

PMID- 26000058
TI  - Cell or cell membrane-based drug delivery systems.
AB  - Natural cells have been explored as drug carriers for a long period. They have
      received growing interest as a promising drug delivery system (DDS) until
      recently along with the development of biology and medical science. The synthetic
      materials, either organic or inorganic, are found to be with more or less
      immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are
      endogenous and thought to be much safer and friendlier. Furthermore, in view of
      their host attributes, they may achieve different biological effects and/or
      targeting specificity, which can meet the needs of personalized medicine as the
      next generation of DDS. In this review, we summarized the recent progress in cell
      or cell membrane-based DDS and their fabrication processes, unique properties and
      applications, including the whole cells, EVs and cell membrane coated
      nanoparticles. We expect the continuing development of this cell or cell membrane
      based DDS will promote their clinic applications. 

PMID- 26000060
TI  - Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response
      for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.
AB  - To enhance effective drug accumulation in drug-resistant tumors, a site-specific
      drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in
      response to tumor extracellular and intracellular pH. This system could firstly
      release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize'
      vasculature and facilitate drug internalization to tumors efficiently, and then
      initiate the secondary pH-response to set the conjugated active anticancer drug
      (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4
      and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG
      Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX
      sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp
      DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with
      reduced toxicity. These results suggested that this site-specific drug-releasing
      system could be exploited as a promising treatment for cancers with repeated
      administration. 

PMID- 26000061
TI  - Erythropoietin improves the accumulation and therapeutic effects of carboplatin
      by enhancing tumor vascularization and perfusion.
AB  - Recombinant human erythropoietin (rhuEpo) is currently under debate for the
      treatment of chemotherapy-induced anemia due to clinical trials showing adverse
      effects in Epo-treated patients and the discovery of the erythropoietin-receptor
      (EpoR) in tumor and endothelial cells. Here, using Epo-Cy5.5 as theranostic near
      infrared fluorescent probe we analyzed the effects of rhuEpo as co-medication to
      carboplatin in non-small-cell-lung-cancer (NSCLC)-xenografts with different tumor
      cell EpoR-expression (H838 ~8-fold higher than A549). Nude mice bearing
      subcutaneous A549 and H838 NSCLC-xenografts received either only carboplatin or
      carboplatin and co-medication of rhuEpo in two different doses. Tumor sizes and
      relative blood volumes (rBV) were longitudinally measured by 3D-contrast-enhanced
      ultrasound (3D-US). Tumoral EpoR-levels were determined by combined fluorescence
      molecular tomography (FMT)/ micro computed tomography (uCT) hybrid imaging. We
      found that rhuEpo predominantly acted on the tumor endothelium. In both
      xenografts, rhuEpo co-medication significantly increased vessel densities,
      diameters and the amount of perfused vessels. Accordingly, rhuEpo induced EpoR
      phoshorylation and stimulated proliferation of endothelial cells. However,
      compared with solely carboplatin-treated tumors, tumor growth was significantly
      slower in the groups co-medicated with rhuEpo. This is explained by the Epo
      mediated vascular remodeling leading to improved drug delivery as obvious by a
      more than 2-fold higher carboplatin accumulation and significantly enhanced tumor
      apoptosis. In addition, co-medication of rhuEpo reduced tumor hypoxia and
      diminished intratumoral EpoR-levels which continuously increased during
      carboplatin (Cp) -treatment. These findings suggest that co-medication of rhuEpo
      in well balanced doses can be used to improve the accumulation of anticancer
      drugs. Doses and indications may be personalized and refined using theranostic
      EpoR-probes. 

PMID- 26000062
TI  - Global low-frequency motions in protein allostery: CAP as a model system.
AB  - Allostery is a fundamental process by which ligand binding to a protein alters
      its activity at a distant site. There is considerable evidence that allosteric
      cooperativity can be communicated by the modulation of protein dynamics without
      conformational change. The Catabolite Activator Protein (CAP) of Escherichia coli
      is an important experimental exemplar for entropically driven allostery. Here we
      discuss recent experimentally supported theoretical analysis that highlights the
      role of global low-frequency dynamics in allostery in CAP and identify how
      allostery arises as a natural consequence of changes in global low-frequency
      protein fluctuations on ligand binding.

PMID- 26000063
TI  - Design of Economic Evaluations of Mindfulness-Based Interventions: Ten
      Methodological Questions of Which to Be Mindful.
AB  - Mindfulness-based interventions (MBIs) are being increasingly applied in a
      variety of settings. A growing body of evidence to support the effectiveness of
      these interventions exists and there are a few published cost-effectiveness
      studies. With limited resources available within public sectors (health care,
      social care, and education), it is necessary to build in concurrent economic
      evaluations alongside trials in order to inform service commissioning and policy.
      If future research studies are well-designed, they have strong potential to
      investigate the economic impact of MBIs. The particular challenge to the health
      economist is how best to capture the ways that MBIs help people adjust to or
      build resilience to difficult life circumstances, and to disseminate effectively
      to enable policy makers to judge the value of the contribution that MBIs can make
      within the context of the limited resourcing of public services. In anticipation
      of more research worldwide evaluating MBIs in various settings, this article
      suggests ten health economics methodological design questions that researchers
      may want to consider prior to conducting MBI research. These questions draw on
      both published standards of good methodological practice in economic evaluation
      of medical interventions, and on the authors' knowledge and experience of
      mindfulness-based practice. We argue that it is helpful to view MBIs as both
      complex interventions and as public health prevention initiatives. Our
      suggestions for well-designed economic evaluations of MBIs in health and other
      settings, mirror current thinking on the challenges and opportunities of public
      health economics.

PMID- 26000064
TI  - A Framework for Supervision for Mindfulness-Based Teachers: a Space for Embodied
      Mutual Inquiry.
AB  - Over recent decades, there has been an exponential growth in mindfulness-based
      interventions (MBIs). To disseminate MBIs with fidelity, care needs to be taken
      with the training and supervision of MBI teachers. A wealth of literature exists
      describing the process and practice of supervision in a range of clinical
      approaches, but, as of yet, little consideration has been given to how this can
      best be applied to the supervision of MBI teachers. This paper articulates a
      framework for supervision of MBI teachers. It was informed by the following: the
      experience of eight experienced mindfulness-based supervisors, the literature and
      understandings from MBIs, and by the authors' experience of training and
      supervision. It sets out the nature and distinctive features of mindfulness-based
      supervision (MBS), representing this complex, multilayered process through a
      series of circles that denote its essence, form, content and process. This paper
      aims to be a basis for further dialogue on MBS, providing a foundation to
      increase the availability of competent supervision so that MBIs can expand
      without compromising integrity and efficacy.

PMID- 26000066
TI  - Men Purchase, Women Use: Coping with Domestic Electrical Appliances in Rural
      China.
AB  - Based on a field study in a village in the northern plain of China, this paper
      reviews three different types in how Han-Chinese rural people have coped with
      domestic electrical appliances during the last 40-odd years of electrification.
      The aim of this paper is to offer an ethnographic study of the complex relations
      between technology and social life in a Chinese rural setting and to explore the
      logic and dynamics whereby rural populations confront and integrate new technical
      products into their everyday life. This paper is divided into three main parts:
      following the introduction on the "everyday technology approach" and background
      information about the field site, the author next gives a brief historical
      description of the electrification process in rural China. The third part is
      dedicated to the ethnographic data concerning five appliances: electric light,
      water pump, TV, washing machine and water boiler-cooler. The paper concludes with
      a discussion of issues concerning appropriation of new technology in the wider
      background of society/economy/state and everyday habitus, questioning how well
      conventional oppositional dichotomies like female/male, masculinity/feminity
      serve as analytical frameworks.

PMID- 26000065
TI  - Common Factors of Meditation, Focusing, and Cognitive Behavioral Therapy:
      Longitudinal Relation of Self-Report Measures to Worry, Depressive, and Obsessive
      Compulsive Symptoms Among Nonclinical Students.
AB  - Meditation has a long tradition with substantial implications for many
      psychotherapies. It has been postulated that meditation may cultivate therapeutic
      processes similar to various psychotherapies. A previous study used joint factor
      analysis to identify five common factors of items of scales purported to capture
      psychological states cultivated by meditation, focusing, and cognitive behavioral
      therapy, namely, refraining from catastrophic thinking, logical objectivity, self
      observation, acceptance, and detached coping. The present study aimed to extend
      previous research on these five factors by examining their longitudinal
      relationship to symptoms of depression, obsession and compulsion, and worrying,
      with two correlational surveys without intervention. Potential mediators of their
      effect on worrying were also explored. Longitudinal questionnaire studies from
      two student samples (n = 157 and 232, respectively) found that (a) detached
      coping was inversely related to obsessive-compulsive symptoms about 5 weeks
      later; (b) detached coping was inversely related to depressive symptoms about 5
      weeks later; (c) refraining from catastrophic thinking was inversely related to
      worrying, while self-observation was positively related to worrying about 2
      months later; and (d) the relation of refraining from catastrophic thinking to
      worrying was mediated by negative beliefs about worrying, while the relation of
      self-observation to worrying was mediated by negative beliefs about worrying and
      monitoring of one's cognitive processes. As refraining from catastrophic thinking
      involves being detached from one's negative thinking and detached coping involves
      distancing oneself from external circumstances and problems, the results suggest
      that distancing attitudes are useful for long-term reduction of various
      psychological symptoms.

PMID- 26000067
TI  - Neuroendocrine tumor of the gallbladder.
AB  - BACKGROUND: The primary neuroendocrine tumors of the gallbladder are very rare,
      representing 0.2% of all neuroendocrine tumors. The definite diagnosis is
      incidental in most cases. CASE REPORT: A 60-year-old male patient presented with
      a one-month history of epigastric pain and jaundice, itching, flushing, cough and
      wheezing. Ultrasound demonstrated the gallbladder containing multiple stones,
      with wall thickening and an adjacent liver lesion. Additionally, those structures
      showed noticeable contrast enhancement in CT and MRI. Histopathological
      examination revealed a primary gallbladder neuroendocrine tumor. CONCLUSIONS:
      Though a rare entity, primary neuroendocrine tumor should be considered in the
      differential diagnosis of gallbladder cancers.

PMID- 26000068
TI  - CT and MR Imaging in a Large Series of Patients with Craniofacial Fibrous
      Dysplasia.
AB  - BACKGROUND: In this retrospective review of patients with craniofacial fibrous
      dysplasia (FD), the clinical and radiological findings of CT and MR scan were
      analyzed. MATERIAL/METHODS: The study material included 32 patients, at 9 to 68
      years of age that were directed for differential diagnostics of several disorders
      in the head. We recorded CT and MRI data related to the lesion number, location,
      sidedness, appearance, and sex of the cases with craniofacial FD. RESULTS: Of 32
      patients involved in this study, 17 had monostotic and 15 had polyostotic
      involvement pattern. Bones most commonly involved by monostotic involvement in
      females were, in descending order, mandibular, maxillary, and sphenoid bones,
      while the sphenoid bone was involved the most in males. Leontiasis ossea was
      observed in 2 patients. Sclerotic and mixed lesion types were more common in both
      females and males. In T1- and T2-weighted MRI sequences, hypointensity was more
      common compared to hyperintensity or heterogeneous intensity. The type of
      enhancement of lesions was found similar after contrast medium administration.
      CONCLUSIONS: In the presence of craniofacial FD during CT or MRI imaging of the
      head, a detailed description of FD lesions may provide an important clinical
      benefit by increasing radiological experience during the diagnostics of this rare
      disorder.

PMID- 26000069
TI  - Trichobezoar, rapunzel syndrome, tricho-plaster bezoar - a report of three cases.
AB  - BACKGROUND: Trichobezoar is an uncommon entity observed mostly in young women.
      Symptoms in presenting patients are usually due to the large mass of the bezoar
      or malabsorption of nutrients. Trichobezoar is almost always associated with
      trichotillomania and trichophagia. CASE REPORT: Three teenage girls, aged 13, 15,
      and 16, were diagnosed due to palpable epigastric masses. Additionally the oldest
      patient presented with symptoms of ileus while the other two patients had weight
      loss and anaemia. Besides the 15-year-old patient complained of paroxysmal
      abdominal pains. Patients were subjected to plain radiographic examinations of
      abdomen which revealed large epigastric tumours, with additional calcifications
      observed in the youngest girl. Subsequent gastroscopy (the 15-year-old patient)
      or ultrasonographic examination and computed tomography scans (13- and 16-year
      old patients) allowed to establish the diagnosis of giant bezoars: trichobezoars
      in two older patients and tricho-plaster bezoar in the youngest one. All the
      tumours were surgically resected and psychiatric treatment was undertaken.
      CONCLUSIONS: 1. Trichobezoar should be taken into consideration in differential
      diagnosis of epigastric tumours in children, especially teenage girls. 2. The
      conventional ultrasonographic and radiographic examinations of the abdomen are
      insufficient for determination of the nature of the mass. A thorough medical
      history interview and clinical examination may give directions regarding the
      further diagnosis.3. Trichotillomania and trichophagia are obsessive-compulsive
      disorders, and therefore patients with trichobezoars should be under psychiatric
      care to prevent recurrence of the disease.

PMID- 26000070
TI  - Brachiocephalic Vein Stenting and Body-Floss Technique as a Treatment of CVD in
      Dialysis-Dependent Patient - Case Report and Literature Review.
AB  - BACKGROUND: Given the increasing number of elderly hemodialysis-dependent
      patients with concomitant chronic diseases the successful creation and
      maintenance of reliable vascular access become a real challenge. In current
      literature central vein disease (CVD) is defined as at least 50% narrowing up to
      total occlusion of central veins of the thorax including superior vena cava
      (SVC), brachiocephalic (BCV), subclavian (SCV) and internal jugular vein (IJV).
      The incidence of CVD has been reported to be as high as 23% in the total dialysis
      population and 41% in those with access related complains. CASE REPORT: 61-year
      old man has been admitted to the local radiology department with symptoms of the
      superior vena cava syndrome. The venography revealed occlusion of the right
      brachiocephalic vein. Due to Tortuosity and lack of stamp of right subclavian
      vein contributed to the decision to perform recanalization by "body floss"
      technique. In a further step we have performed PTA of obstructed vein segment
      using 7*40 mm balloon. Due to the presence of residual stenosis it was decided to
      implant two self - expanding stents 10*40 mm. After the procedure the patient was
      discharged in good condition and transferred to dialysis center. CONCLUSIONS:
      Main objective was the salvage of a functioning arteriovenous fistula. Performed
      endovascular intervention is a safe and effective approach to correct CVD for a
      short term. To ensure long lasting effects the patient will require enhanced
      follow-up and inevitable reinterventions. For that matter, prevention of CVD
      remains critical.

PMID- 26000071
TI  - miR-103 Regulates Oxidative Stress by Targeting the BCL2/Adenovirus E1B 19 kDa
      Interacting Protein 3 in HUVECs.
AB  - Oxidative stress plays a critical role in cardiovascular diseases. Salidroside, a
      glycoside from Rhodiola rosea, has been used as an antioxidative therapy for
      oxidative injury in cardiac diseases. However, the mechanism underlying its
      antioxidant effect needs to be elucidated. Treatment of HUVECs with H2O2
      significantly decreased the expression of miR-103 in a dose- and time-dependent
      manner, whereas pretreatment with salidroside significantly inhibited this
      decrease. Subsequent analysis showed that overexpression of miR-103 abrogated
      cell activity and ROS production induced by H2O2. Bcl2/adenovirus E1B 19 kDa
      interacting protein 3 (BNIP3) was determined to be a novel miR-103 target in
      HUVECs. Interestingly, H2O2 treatment upregulated BNIP3 expression; in turn, this
      effect was inhibited by pretreatment with salidroside. Further studies confirmed
      that the knockdown of BNIP3 enhanced cell activity and suppressed the ROS
      production induced by H2O2. These results demonstrated for the first time that
      salidroside protects HUVECs in part by upregulating the expression of miR-103,
      which mediates BNIP3 downregulation and plays an important role in the
      cytoprotective actions. 

PMID- 26000073
TI  - Rich man, poor man: socioeconomic adversity and brain development.

PMID- 26000072
TI  - Effect of myricetin, pyrogallol, and phloroglucinol on yeast resistance to
      oxidative stress.
AB  - The health beneficial effects of dietary polyphenols have been attributed to
      their intrinsic antioxidant activity, which depends on the structure of the
      compound and number of hydroxyl groups. In this study, the protective effects of
      pyrogallol, phloroglucinol, and myricetin on the yeast Saccharomyces cerevisiae
      were investigated. Pyrogallol and myricetin, which have a pyrogallol structure in
      the B ring, increased H2O2 resistance associated with a reduction in
      intracellular oxidation and protein carbonylation, whereas phloroglucinol did not
      exert protective effects. The acquisition of oxidative stress resistance in cells
      pretreated with pyrogallol and myricetin was not associated with an induction of
      endogenous antioxidant defences as assessed by the analysis of superoxide
      dismutase and catalase activities. However, myricetin, which provided greater
      stress resistance, prevented H2O2-induced glutathione oxidation. Moreover,
      myricetin increased the chronological lifespan of yeast lacking the mitochondrial
      superoxide dismutase (Sod2p), which exhibited a premature aging phenotype and
      oxidative stress sensitivity. These findings show that the presence of hydroxyl
      groups in the ortho position of the B ring in pyrogallol and myricetin
      contributes to the antioxidant protection afforded by these compounds. In
      addition, myricetin may alleviate aging-induced oxidative stress, particularly
      when redox homeostasis is compromised due to downregulation of endogenous
      defences present in mitochondria. 

PMID- 26000074
TI  - Review: the future of the mind: the scientific quest to understand, enhance, and
      empower the mind.
AB  - In Jerome Kagan's review of The Future of the Mind by physicist and futurist
      Michio Kaku, Kagan leans on his own experience as co-director of the Harvard
      Mind/Brain/Behavior Interfaculty Initiative to explore a book that imagines a
      world where we will have the power to record, store, and transmit signals of
      brain activity, and where interchangeable thoughts and self-aware robots will be
      part of everyday life. 

PMID- 26000075
TI  - One of a kind: the neurobiology of individuality.

PMID- 26000077
TI  - Retrospective study of facial nerve function following temporomandibular joint
      arthroplasty using the endaural approach.
AB  - The aim of this retrospective case-control study is to evaluate the incidence of
      facial nerve injury associated with temporomandibular joint (TMJ) arthroplasty
      using the endaural approach for the treatment of TMJ pathology. The sample
      consisted of 36 consecutive patients who underwent TMJ arthroplasty. A total of
      39 approaches were performed through an endaural incision. Patients undergoing
      total joint replacement and/or with preexisting facial nerve dysfunction were
      excluded from the study. Five patients were lost to follow-up and were excluded
      from the study. Facial nerve function of all patients was clinically evaluated by
      resident physicians preoperatively, postoperatively, and at follow-up
      appointments. Facial nerve injury was determined to have occurred if the patient
      was unable to raise the eyebrow or wrinkle the forehead (temporalis branch),
      completely close the eyelids (zygomatic branch), or frown (marginal mandibular
      branch). Twenty-one of the 36 patients or 22 of the 39 approaches showed signs of
      facial nerve dysfunction following TMJ arthroplasty. This included 12 of the 21
      patients who had undergone previous TMJ surgery. The most common facial nerve
      branch injured was the temporal branch, which was dysfunctional in all patients
      either as the only branch injured or in combination with other branches. By the
      18th postoperative month, normal function had returned in 19 of the 22 TMJ
      approaches. Three of the 22 TMJ approaches resulted in persistent signs of facial
      nerve weakness 6 months after the surgery. This epidemiological study revealed a
      low incidence of permanent facial nerve dysfunction. A high incidence of
      temporary facial nerve dysfunction was seen with TMJ arthroplasty using the
      endaural approach. Current literature reveals that the incidence of facial nerve
      injury associated with open TMJ surgery ranges from 12.5 to 32%. The temporal
      branch of the facial nerve was most commonly affected, followed by 4 of the 22
      approaches with temporary zygomatic branch weakness. Having undergone previous
      TMJ surgery did not increase the incidence of facial nerve injury using the
      endaural approach. This information is important for patients and surgeons in the
      postoperative period, as a majority of patients will experience recovery of nerve
      function. 

PMID- 26000076
TI  - Alcohol consumption and interpersonal injury in a pediatric oral and
      maxillofacial trauma population: a retrospective review of 1,192 trauma patients.
AB  - The social, financial, and health implications of adult alcohol-related oral and
      maxillofacial trauma have been recognized for several years. Affordability and
      widespread accessibility of alcohol and issues of misuse in the pediatric trauma
      population have fostered concerns alcohol may be similarly implicated in young
      patients with orofacial trauma. The aim of this study was to review data of
      pediatric facial injuries at a regional maxillofacial unit, assess the prevalence
      of alcohol use, and review data of patients sustaining injury secondary to
      interpersonal violence. This study is a retrospective, 3-year review of a
      Regional Maxillofacial Unit (RMU) trauma database. Inclusion criterion was
      consecutive facial trauma patients under 16 years of age, referred to RMU for
      further assessment and/or management. Alcohol use and injuries sustained were
      reviewed. Of 1,192 pediatric facial trauma patients, 35 (2.9%) were associated
      with alcohol intake. A total of 145 (12.2%) alleged assault as the mechanism of
      injury, with older (12-15 years) (n = 129; 88.9%), male (n = 124; 85.5%) (p <
      0.001) patients commonly involved and alcohol use implicated in 26 (17.9%)
      presentations. A proportion of vulnerable adolescents misuse alcohol to the risk
      of traumatic facial injury, and prospective research to accurately determine any
      role of alcohol in the pediatric trauma population is essential. 

PMID- 26000078
TI  - Development and Clinical Evaluation of MatrixMANDIBLE Subcondylar Plates System
      (Synthes).
AB  - In this article, authors report the different steps of development and clinical
      validation of MatrixMANDIBLE Subcondylar Plates (Synthes, Soletta, Switzerland),
      a specialized osteosynthesis system developed by Synthes during the past 4 years.
      Between 2009 and 2013, a total of 62 patients were treated for subcondylar and
      condylar neck fractures via a preauricular or retromandibular/transparotid
      approach. The MatrixMANDIBLE Subcondylar Plates System consists of a Trapezoidal
      Plate, a three-dimensional (3D) 4-hole 1.0-mm plate for smaller fracture areas,
      the Lambda Plate, a 7-hole 1.0-mm linear plate which mimics the two miniplates
      technique, and the Strut Plate, a 3D 1.0-mm plate with great versatility of
      employment. All devices satisfy the principles of a functionally stable
      osteosynthesis as stated by Champy et al. None of the plates broke and no
      macroscopic condylar displacement was noted on radiological follow-up. Clinical
      and functional parameters assessed at 6 months postoperative (mandibular range of
      motion, pain, dental occlusion) were almost restored. MatrixMANDIBLE Subcondylar
      Plates System (Synthes) has proved to provide sufficient mechanical stiffness and
      anatomically accurate fracture reduction to avoid major postoperative drawbacks
      of subcondylar and condylar neck fractures. 

PMID- 26000080
TI  - A case series of rapid prototyping and intraoperative imaging in orbital
      reconstruction.
AB  - In Christchurch Hospital, rapid prototyping (RP) and intraoperative imaging are
      the standard of care in orbital trauma and has been used since February 2013. RP
      allows the fabrication of an anatomical model to visualize complex anatomical
      structures which is dimensionally accurate and cost effective. This assists
      diagnosis, planning, and preoperative implant adaptation for orbital
      reconstruction. Intraoperative imaging involves a computed tomography scan during
      surgery to evaluate surgical implants and restored anatomy and allows the
      clinician to correct errors in implant positioning that may occur during the same
      procedure. This article aims to demonstrate the potential clinical and cost
      saving benefits when both these technologies are used in orbital reconstruction
      which minimize the need for revision surgery. 

PMID- 26000079
TI  - Retrocaruncular approach for the repair of medial orbital wall fractures: an
      anatomical and clinical study.
AB  - The aim of this article is to investigate a retrocaruncular approach for
      repairing medial orbital wall fractures. A total of 10 fresh cadaver orbits were
      dissected to investigate a transconjunctival approach to the orbit posterior to
      the caruncle. Medical records of consecutive patients with medial orbital wall
      fractures repaired via a retrocaruncular incision at Wilmer Eye Institute over a
      10-year period were retrospectively reviewed. The study was approved by the Johns
      Hopkins Medical Institution's Institutional Review Board. Feasibility of this
      approach was clearly demonstrated on all cadavers. Horner muscle was observed to
      be directly attached to the caruncle and remained undisturbed throughout the
      retrocaruncular approach. For each of the 174 patients reviewed, this approach
      allowed successful access to the fracture and proper implant placement. The
      origin of the inferior oblique muscle was divided in only 19 patients. Sutures
      were not used for conjunctival incision closure in any patient. For 120 patients
      who underwent acute repair, the percentage with enophthalmos (>= 2 mm) decreased
      from 34% preoperatively to 4% postoperatively; extraocular motility deficit
      decreased from 41 to 11%. Postoperative complications included recurrence of the
      preexisting retrobulbar hemorrhage, conjunctival granuloma, and temporary
      torsional diplopia, each in one patient. The retrocaruncular transconjunctival
      incision is an effective and safe approach for repairing medial orbital wall
      fractures with minimal complications. The retrocaruncular incision offers
      advantages over dividing the caruncle because Horner muscle is left undisturbed,
      and the incision heals well without suturing. 

PMID- 26000081
TI  - Finite element analysis of patient-specific condyle fracture plates: a
      preliminary study.
AB  - Various patterns of internal fixation of mandibular condyle fractures have been
      proposed in the literature. This study investigates the stability of two patient
      specific implants (PSIs) for the open reduction and internal fixation of a
      subcondylar fracture of the mandible. A subcondylar fracture of a mandible was
      simulated by a series of finite element models. These models contained
      approximately 1.2 million elements, were heterogeneous in bone material
      properties, and also modeled the muscles of mastication. Models were run assuming
      linear elasticity and isotropic material properties for bone. The stability and
      von Mises stresses of the simulated condylar fracture reduced with each of the
      PSIs were compared. The most stable of the plate configurations examined was PSI
      1, which had comparable mechanical performance to a single 2.0 mm straight four
      hole plate. 

PMID- 26000082
TI  - Experience with mandibular reconstruction using transport-disc-distraction
      osteogenesis.
AB  - The goal of transport-disc-distraction osteogenesis (TDDO) is to restore bone
      continuity by using in-situ bone. It may be useful following trauma, gunshot
      injuries, or tumor ablation, especially when there may be contraindications at
      the donor site or for prolonged surgery. To the best of the authors' knowledge,
      this is the first time TDDO has been used for mandibular reconstruction reporting
      additional procedures, which include osseointegrated dental implants
      rehabilitation and orthognathic surgery. A retrospective study is performed
      analyzing all mandibular reconstruction cases that may be suitable for
      distraction from January 2006 to December 2011. A thorough description of the
      documented cases includes details about sex, gender, complications, duration of
      hospitalization, etiology, size, and location of the defect. Eight cases of
      mandibular reconstruction were included. Six cases correspond to mandibular
      ameloblastoma. The remaining two cases were mandibular gunshot comminuted
      fractures. Range of the defects was from 45 to 60 mm. Length of the transport
      disc was 15 to 20 mm. Protocolized technique consisted of 5 days of latency
      period, 19 to 45 days of activation term (average 30 days), and 8 to 12 weeks for
      consolidation. Mean distraction length achieved was 40.45 mm. We can conclude
      that TDDO is an alternative to conventional and more invasive procedures, when we
      face severe segmental mandibular defects reconstruction. It shows the potential
      to restore a better anatomical bone regeneration, also providing soft tissues and
      reducing donor-site morbidity. Patients' education and awareness about the proper
      use of the transport-disc-distraction device is important to optimize functional
      outcomes. 

PMID- 26000083
TI  - Biomechanical comparison of four mandibular angle fracture fixation techniques.
AB  - The aim of this study was to make a comparison of the biomechanical behavior of
      four different internal fixation systems for mandibular angle fractures. A total
      of 40 polyurethane mandible replicas were employed with different fixation
      methods: group 1SP, one 2.0-mm four-hole miniplate; group 2PPL, two 2.0-mm four
      hole parallel miniplates; group 3DP, one 3D 2.0-mm four-hole miniplate; and group
      3DPP, one 3D 2.0-mm eight-hole miniplate. Each group was subjected to incisal or
      homolateral molar region loading. The load resistance values were measured at
      load application causing tip displacement of 1, 3, and 5 mm, and at the time at
      which the system achieves its maximum strength (MS). Means and standard
      deviations were compared among groups using analysis of variance and the Tukey
      test. Group 2PPL showed higher strength for all the displacements. For incisal
      loading, no statistically significant differences were found between groups 1SP,
      3DP, and 3DPP. For molar loading, group 1SP and 3DPP showed statistically
      significant differences. For MS testing, group 1SP and 2PPL showed statistically
      significant differences in incisal loading; group 1SP and 3DP showed no
      statistically significant differences; and group 3DPP showed lower values of
      strength. Two parallel miniplates provide the most favorable mechanical behavior
      under the conditions tested. 

PMID- 26000084
TI  - Remarkable Triple Pleomorphic Adenoma Affecting both Parotid and Submandibular
      Glands.
AB  - The objective of this article is to present the first case reported in the
      literature of metachronous pleomorphic adenoma of bilateral parotid glands and
      submaxillary gland. The authors report the case of a 27-year-old female with
      metachronous mixed tumors in her right parotid and submandibular glands. The
      patient has no history of previous radiotherapy. All three lesions were diagnosed
      by fine-needle aspiration. The histopathologic evaluation of all three major
      salivary gland masses demonstrated pleomorphic adenomas, with no occult
      malignancy observed on serial sections. The presentation of pleomorphic adenomas
      in the parotids and submandibular glands probably represents three unrelated
      primary sites of tumor, yet the possibility of metastasis from one gland to the
      other cannot be excluded. 

PMID- 26000085
TI  - Ellis-van Creveld Syndrome with Sagittal Craniosynostosis.
AB  - Ellis-van Creveld syndrome (EVC) is a rare disorder (the incidence is estimated
      at around 7/1,000,000) characterized by the clinical tetrad of chondrodystrophy,
      polydactyly, ectodermal dysplasia, and cardiac anomalies. Sagittal synostosis is
      characterized by a dolichocephalic head shape resulting from premature fusion of
      the sagittal suture. Both are rare disorders, which have never been reported
      together. We present a case of EVC and sagittal synostosis. We report the
      clinical features of a Hispanic boy with EVC and sagittal craniosynostosis who
      underwent cranial vault remodeling. The presentation of this patient is gone over
      in detail. A never before reported case of EVC and sagittal synostosis is
      presented in detail. 

PMID- 26000086
TI  - Condylar osteochondroma treated with total condylectomy and preservation of the
      articular disc: a case report.
AB  - Osteochondroma is frequently found in the general skeleton but is rare in the
      condylar region of the mandible. We report a case of an osteochondroma of large
      size and rapid growth in the mandibular condyle, which was treated with total
      condylectomy and condylar replacement with a costochondral graft and preservation
      of the articular disc. In cases with a healthy and well-positioned articular
      disc, it may be preserved with no need of disc repositioning. 

PMID- 26000087
TI  - Beveled osteotomies in lateral orbitotomy using a customized rotating bone saw
      for orbital neoplasms.
AB  - This study aims to develop a novel method of beveled osteotomy for lateral
      orbitotomy using a customized 21-mm stainless steel rotating saw in lateral
      orbitotomy and to evaluate the outcome of a novel beveled osteotomy in lateral
      orbitotomy. This article presents a case series (19 orbits from 18 patients) of
      lateral orbitotomies for excision biopsy of orbital neoplasms, over a 10-year
      period (from September 2001 to October 2011). It is a retrospective observational
      study. The surgeries were performed under the primary service of one surgeon (M.
      D. D. S.), the author of this study. All patients were treated via beveled
      osteotomies in lateral orbitotomy using a stainless steel, 21 mm diameter,
      customized rotating bone saw. Preoperative and postoperative measurements were
      tabulated and statistically analyzed. The case series demonstrated that beveled
      osteotomies in lateral orbitotomy using a stainless steel, 21 mm diameter,
      customized rotating bone saw was technically possible and provided access to
      lateral subperiorbital, peripheral, and central surgical spaces. The exposure was
      ample for excision biopsy of all neoplasms in this study. No patient needed the
      use of miniplate hardware in repositioning the lateral orbital wall nor
      complained of a palpable deformity of the lateral orbital wall. The wound healing
      was rapid, with minimal tissue distortion or scars. There were two patients who
      developed skin burns, but neither required a cosmetic surgery to correct scarring
      from the burn. It was concluded that the modified technique of beveled
      osteotomies in lateral orbitotomy provides excellent access to the lateral
      subperiorbital, peripheral and central surgical spaces. The exposure was adequate
      for excision biopsy of all neoplasms in this study. The technique promotes
      osseous union without the use of miniplate hardware. The use of a stainless steel
      21 mm diameter customized rotating bone saw facilitated the successful outcome of
      the beveled technique. 

PMID- 26000088
TI  - Ascher syndrome: report of a case with early manifestations.
AB  - Ascher syndrome is a disease of unknown etiology first described in 1920 by
      Ascher, an ophthalmologist from Prague. It presents with recurrent edema of the
      lip and upper eyelid resulting in double lip and blepharochalasis. In 10% of
      cases the idiopathic nontoxic thyroid enlargement also occurs. Because of its
      rarity, it is often undiagnosed. A case of early onset is presented with its
      respective surgical treatment and outcome. 

PMID- 26000089
TI  - Isolated bilateral mandibular angle fractures: an extensive literature review of
      the rare clinical phenomenon with presentation of a classical clinical model.
AB  - Bilateral angle fractures are a rare clinical phenomenon in contrast to the
      incidence of unilateral angle fractures. However, the rarity has garnered less
      attention in spite of the uniqueness of fracture pattern and distinctive
      biomechanics. This article is a detailed review on the etiology, clinical
      presentation, and management of bilateral angle fractures with the presentation
      of an interesting case. The bilateral angle fracture reported is a untreated,
      malunited fracture representing an ideal clinical model to study its
      biomechanics. The clinical features were anterior open bite, increased facial
      height, and temporomandibular joint tenderness. The management included osteotomy
      at the malunion and miniplate osteosynthesis. Bilateral angle fracture presents
      mandible in three independent fragments (left angle, right angle, and
      intermediate corpus), each with strong muscles acting in different vectors. This
      makes the fracture vulnerable to severe displacing forces and unfavorable to
      achieve the optimal reduction, stability, and healing. This necessitates
      comprehension of the biomechanical forces involved to avoid malunion following
      fixation. The article details the complex biomechanics of mandibular angle and
      its clinical implications in the rare event of bilateral angle fractures. It
      describes the necessity for a systematic approach and ideal osteosynthesis
      principles to achieve maximal treatment outcomes and minimal complications. 

PMID- 26000091
TI  - Channeling Remittances to Education: A Field Experiment Among Migrants from El
      Salvador.
AB  - We implement a randomized experiment offering Salvadoran migrants matching funds
      for educational remittances, which are channeled directly to a beneficiary
      student in El Salvador chosen by the migrant. The matches lead to increased
      educational expenditures, higher private school attendance, and lower labor
      supply of youths in El Salvador households connected to migrant study
      participants. We find substantial "crowd-in" of educational investments: for each
      $1 received by beneficiaries, educational expenditures increase by $3.72. We find
      no shifting of expenditures away from other students, and no effect on
      remittances.

PMID- 26000090
TI  - Cranioplasty for large-sized calvarial defects in the pediatric population: a
      review.
AB  - Large-sized calvarial defects in pediatric patients pose a reconstructive
      challenge because of children's unique physiology, developing anatomy, and
      dynamic growth. We review the current literature and outcomes with autologous and
      alloplastic cranioplasty in the pediatric population. 

PMID- 26000092
TI  - Biguanides and targeted anti-cancer treatments.

PMID- 26000093
TI  - Trop2 and its overexpression in cancers: regulation and clinical/therapeutic
      implications.
AB  - Trop2 is a transmembrane glycoprotein encoded by the Tacstd2 gene. It is an
      intracellular calcium signal transducer that is differentially expressed in many
      cancers. It signals cells for self-renewal, proliferation, invasion, and
      survival. It has stem cell-like qualities. Trop2 is expressed in many normal
      tissues, though in contrast, it is overexpressed in many cancers and the
      overexpression of Trop2 is of prognostic significance. Several ligands have been
      proposed that interact with Trop2. Trop2 signals the cells via different pathways
      and it is transcriptionally regulated by a complex network of several
      transcription factors. Trop2 expression in cancer cells has been correlated with
      drug resistance. Several strategies target Trop2 on cancer cells that include
      antibodies, antibody fusion proteins, chemical inhibitors, nanoparticles, etc.
      The in vitro studies and pre-clinical studies, using these various therapeutic
      treatments, have resulted in significant inhibition of tumor cell growth both in
      vitro and in vivo in mice. A clinical study is underway using IMMU-132 (hrS7
      linked to SN38) in patients with epithelial cancers. This review describes
      briefly the various characteristics of cancer cells overexpressing Trop2 and the
      potential application of Trop2 as both a prognostic biomarker and as a
      therapeutic target to reverse resistance. 

PMID- 26000094
TI  - Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma.
AB  - Lung adenocarcinoma is often discovered as metastatic disease with very poor
      prognosis. However, much remains unknown about the mechanisms of lung
      adenocarcinoma tumor progression. In this study we showed that knockdown of
      BUB1B/BUBR1, a critical mitotic checkpoint protein, significantly inhibited
      anchorage-independent growth of lung adenocarcinoma cell lines. In allograft and
      tail vein mouse model studies, BUB1B suppression inhibited primary tumor growth
      and reduced metastasis to the lung and lymph nodes, resulting in prolonged
      survival in both tumor prevention and tumor intervention settings. Mechanistic
      studies revealed that BUB1B knockdown sensitized cells to anoikis. The N-terminal
      region and GLEBS domain of BUB1B were required for its functions in both
      anchorage-independent growth and anoikis resistance, whereas the kinase domain
      was less critical. Overexpression of BUB1B is associated with disease progression
      and poor survival in human lung adenocarcinoma patients. Collectively, these data
      reveal a novel function for BUB1B in mediating anchorage-independent survival and
      growth, thereby facilitating lung adenocarcinoma dissemination during metastasis.
      Thus, targeting BUB1B could provide potential therapeutic benefit in suppressing
      metastasis and prolonging survival in lung adenocarcinoma patients. 

PMID- 26000095
TI  - Drug sensitivity profiling and molecular characteristics of cells from pleural
      effusions of patients with lung adenocarcinoma.
AB  - We propose to assess the therapeutic value of biomarker-guided individualized
      chemotherapy in patients with metastasizing lung adenocarcinoma. In this study,
      we used primary cells from pleural effusions from sixteen patients diagnosed with
      adenocarcinomas originating in the lung and from four patients with no malignant
      diagnosis. The ex vivo drug sensitivity of primary cells was assessed for 32
      chemotherapeutical drugs. Linear regression analyses were performed to examine
      possible correlations between the drug sensitivity, overall survival and
      expression of ERCC1 and RRM1. The ex vivo drug sensitivity profiles of the
      patients revealed considerable heterogeneity in drug response. Vinblastine,
      vinorelbine, paclitaxel and actinomycin D showed high efficiency against 50% of
      the tested primary cells. Significant correlation was detected between the ex
      vivo sensitivity to platinum based drugs and gemcitabine and the level of ERCC1
      and RRM1. No significant correlation was however seen between overall survival
      and drug sensitivity. The heterogeneity of the drug response suggests that
      optimal care of the adenocarcinoma patients should include the determination of
      drug sensitivity of the primary cells and would benefit to use personalized
      therapy. 

PMID- 26000097
TI  - Triptolide and its prodrug minnelide suppress Hsp70 and inhibit in vivo growth in
      a xenograft model of mesothelioma.
AB  - Malignant mesothelioma is a devastating disease with a poor prognosis for which
      there is a clear need for more successful therapeutic approaches. Triptolide, a
      diterpenoid triepoxide, is a highly effective agent against several cancer types
      in animal models. Owing to triptolide's poor solubility in water, a water-soluble
      analog, minnelide, was synthesized. Minnelide is a prodrug of triptolide and is
      activated by exposure to phosphatases that are found in all body tissues,
      including blood. Mesothelioma cells were treated in vitro with minnelide or its
      parent compound, triptolide. Minnelide and triptolide were both found to
      significantly reduce mesothelioma cell viability and induce apoptosis. The level
      of Hsp70, a protein that promotes cancer cell survival, was measured in
      mesothelioma cells before and after treatment with triptolide. Hsp70 levels were
      decreased in a dose-dependent manner. In addition, triptolide sensitized cells to
      gemcitabine and pemetrexed as measured by cell viability. Mice bearing
      mesothelioma flank tumors were treated with daily injections (28 d) of minnelide
      or saline solution and xenograft tumor growth recorded. Mice displayed
      significantly reduced tumor burden. These findings support the clinical
      evaluation of minnelide therapy for mesothelioma. 

PMID- 26000096
TI  - EWS/FLI utilizes NKX2-2 to repress mesenchymal features of Ewing sarcoma.
AB  - In Ewing sarcoma, NKX2-2 is a critical activated target of the oncogenic
      transcription factor EWS/FLI that is required for transformation. However, its
      biological function in this malignancy is unknown. Here we provide evidence that
      NKX2-2 mediates the EWS/FLI-controlled block of mesenchymal features.
      Transcriptome-wide RNA sequencing revealed that NKX2-2 represses cell adhesion
      and extracellular matrix organization genes. NKX2-2-depleted cells form more
      focal adhesions and organized actin stress fibers, and spread over a wider area
      hallmarks of mesenchymally derived cells. Furthermore, NKX2-2 represses the actin
      stabilizing protein zyxin, suggesting that these morphological changes are
      attributable to zyxin de-repression. In addition, NKX2-2-knockdown cells display
      marked increases in migration and substrate adhesion. However, only part of the
      EWS/FLI phenotype is NKX2-2-dependent; consequently, NKX2-2 is insufficient to
      rescue EWS/FLI repression of mesenchymalization. Strikingly, we found that
      EWS/FLI-and NKX22-repressed genes are activated by ZEB2, which was previously
      shown to block Ewing sarcoma epithelialization. Together, these data support an
      emerging theme wherein Ewing sarcoma cells highly express transcription factors
      that maintain an undifferentiated state. Importantly, co-opting epithelial and
      mesenchymal traits by Ewing sarcoma cells may explain how the primary tumor grows
      rapidly while also "passively" metastasizing, without the need for transitions
      toward differentiated states, as in carcinomas. 

PMID- 26000098
TI  - Granulin, a novel STAT3-interacting protein, enhances STAT3 transcriptional
      function and correlates with poorer prognosis in breast cancer.
AB  - Since the neoplastic phenotype of a cell is largely driven by aberrant gene
      expression patterns, increasing attention has been focused on transcription
      factors that regulate critical mediators of tumorigenesis such as signal
      transducer and activator of transcription 3 (STAT3). As proteins that interact
      with STAT3 may be key in addressing how STAT3 contributes to cancer pathogenesis,
      we took a proteomics approach to identify novel STAT3-interacting proteins. We
      performed mass spectrometry-based profiling of STAT3-containing complexes from
      breast cancer cells that have constitutively active STAT3 and are dependent on
      STAT3 function for survival. We identified granulin (GRN) as a novel STAT3
      interacting protein that was necessary for both constitutive and maximal leukemia
      inhibitory factor (LIF)induced STAT3 transcriptional activity. GRN enhanced STAT3
      DNA binding and also increased the time-integrated amount of LIF-induced STAT3
      activation in breast cancer cells. Furthermore, silencing GRN neutralized STAT3
      mediated tumorigenic phenotypes including viability, clonogenesis, and migratory
      capacity. In primary breast cancer samples, GRN mRNA levels were positively
      correlated with STAT3 gene expression signatures and with reduced patient
      survival. These studies identify GRN as a functionally important STAT3
      interacting protein that may serve as an important prognostic biomarker and
      potential therapeutic target in breast cancer. 

PMID- 26000100
TI  - Autoimmunity Highlights: a bridge between the clinic and the laboratory.

PMID- 26000099
TI  - Suberoylanilide hydroxamic acid (SAHA) reverses chemoresistance in head and neck
      cancer cells by targeting cancer stem cells via the downregulation of nanog.
AB  - Acquisition of chemoresistance and metastatic phenotype are the major causes of
      treatment failure and mortality in head and neck squamous cell carcinoma (HNSCC)
      patients. Histone deacetylases (HDACs) have been shown to be overexpressed in
      many tumor types and directly linked to poor prognosis. In this study, we
      demonstrate that HDACs are markedly elevated in HNSCC. HDACs expression was
      further increase in cisplatin resistant cell lines (CisR). In addition, cisplatin
      resistant cells showed enhanced stem cell properties and tumor metastasis.
      Depletion of HDAC1 and 2 in CisR cell lines significantly reversed cisplatin
      resistance and tumorsphere formation. Next, we tested the efficacy of
      Suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, by using both in vitro
      and in vivo models. SAHA significantly inhibited cell proliferation and
      synergistically enhanced the anti-proliferative effects of cisplatin. In
      addition, SAHA significantly decreased tumorsphere formation by markedly reducing
      nanog expression. In a SCID mouse xenograft model, SAHA significantly enhanced
      the anti-tumor effects of cisplatin treatment with no added systemic toxicity.
      Furthermore, SAHA and cisplatin combination treatment significantly decreased
      tumor metastasis and nanog expression, in vivo. Taken together, our results
      suggest that targeting HDACs with SAHA could be an effective treatment strategy
      for the treatment of HNSCC patients. 

PMID- 26000101
TI  - Welcome autoimmunity highlights.

PMID- 26000102
TI  - The antiphospholipid syndrome: a large elephant with many parts or an elusive
      chameleon disguised by many colours?
AB  - The antiphospholipid syndrome (APS) is characterized by a range of clinical
      features (primarily thrombosis and/or obstetric-related), together with the
      presence of antiphospholipid antibody (aPL) as detected by a diverse range of
      laboratory tests. APS remains a significant diagnostic and management challenge
      for clinicians across a wide range of specialties, some 30 years after APS was
      first described as a discrete clinical entity. This is due to ongoing issues
      regarding nomenclature, the diagnosis of APS in individual patients, the
      expanding range of recognized clinical manifestations and of APS-related
      laboratory tests, and management issues in particular APS patient subgroups
      (including obstetric and catastrophic APS). In addition to the presence of
      appropriate clinical features, the diagnosis of APS fundamentally requires the
      finding of positive aPL test result(s), which is hampered by ongoing problems
      with assay reproducibility and standardization. This review focuses on ongoing
      dilemmas and issues related to clinical and laboratory aspects of APS including:
      (1) diagnostic challenges posed by the protean clinical manifestations of APS;
      (2) current nomenclature and recent proposals for revision of the 2006
      international classification criteria; (3) an overview of some key issues related
      to aPL testing; (4) potential pitfalls of applying the APS classification
      criteria as diagnostic criteria; and (5) the controversial subgroups of
      seronegative APS and non-APS aPL positivity. 

PMID- 26000103
TI  - Management of the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is characterized by recurrent venous or arterial
      thromboses, fetal losses and thrombocytopenia in the presence of antiphospholipid
      antibodies, namely lupus anticoagulant, anticardiolipin antibodies or antibodies
      directed to various proteins, mainly beta2 glycoprotein I, or all three. There is
      consensus in treating patients with APS and first venous thrombosis with oral
      anticoagulation to a target international normalized ratio (INR) of 2.0-3.0. A
      recent systematic review recommended a target INR of >3.0 in those patients with
      APS and arterial thrombosis. The approach in women with obstetric manifestations
      of APS is based on the use of aspirin plus heparin. The best treatment for
      patients with the catastrophic variant of the APS is a combination of
      anticoagulation, corticosteroids, and plasma exchange or intravenous
      immunoglobulins. 

PMID- 26000105
TI  - Microscopic enteritis and pathomechanism of malabsorption.
AB  - Microscopic enteritis (ME) is the stage of microscopic and sub-microscopic
      changes (microenteropathy) associated with the symptoms of gluten sensitive
      enteropathy leading to micronutrient deficiencies. It is characterized by subtle
      mucosal abnormalities without prominent inflammation, villous effacement,
      erosions or ulcerations on conventional light microscopy. The intraepithelial
      lymphocytes are usually in normal range <25/100 enterocytes (microenteropathy) or
      increased (lymphocytic enteritis). ME is the entity behind atypical forms of CD
      previously known as potential and latent CD. Systemic inflammation predominantly
      is found to be engaged in pathophysiology of micro-nutrient deficiency even in
      absence of macroscopic mucosal changes. 

PMID- 26000106
TI  - Twenty-eight years with antineutrophil cytoplasmic antibodies (ANCA): how to test
      for ANCA - evidence-based immunology?
AB  - Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and
      primary pauci-immune crescentic glomerulonephritis are associated with
      circulating antineutrophil cytoplasmic autoantibodies (ANCA) (collectively called
      ANCA-associated vasculitides, AAV). Two types of ANCA, one with a cytoplasmic
      fluorescence pattern (C-ANCA) and specificity for proteinase 3 (PR3-ANCA) and the
      other with a perinuclear pattern (P-ANCA) and specificity for myeloperoxidase
      (MPO-ANCA), account for this association and are highly specific markers for
      these vasculitides. AAV most often require therapy with cytotoxic and
      antiinflammatory agents, and hence a well-established diagnosis is mandatory to
      avoid unnecessary and risky treatment. The widespread use of ANCA screening in
      the past decade has resulted in the occurrence of greater numbers of false
      positive results and has led to greater difficulty in test interpretation.
      Methods for ANCA detection have been standardized internationally in large
      multicentre studies and an international consensus statement on testing and
      reporting of ANCA has been pub lished (1999 and 2003). Despite these advances,
      problems with the extended use of ANCA testing in daily clinical practice remain.
      They may be summarized as follows: (1) the basic standards for ANCA testing are
      not uniformly met; (2) there is still controversy over the value of formalin
      fixation of neutrophils in differentiating P-ANCA from antinuclear antibodies
      (what is the place of this substrate in ANCA testing?); (3) the new generation of
      PR3-ANCA and MPO-ANCA ELISAs are more sensitive and specific than
      immunofluorescence testing (should ELISAs replace the immunofluorescence test?);
      and (4) should alternative methods for ANCA detection such as image analysis
      and/or multiplex immunoassays be used for screening? In this paper, we review
      these issues, identify areas of uncertainty, and provide practical guidelines
      where possible. 

PMID- 26000104
TI  - Hepatitis C virus and autoimmunity.
AB  - Hepatitis C virus infection is associated with several extrahepatic
      manifestations. About 60% of patients infected with HCV develop at least one
      extrahepatic manifestation. The majority of these diseases seem to be triggered
      through autoimmune mechanisms, such as autoantibody production, autoreactive T
      cells and complex autoimmune mechanisms leading to systemic autoimmune disorders.
      In this review we categorize these diseases into three groups according to the
      main pathogenetic process involved, in particular B-cell-mediated, T-cell
      mediated and complex autoimmune systemic diseases. 

PMID- 26000107
TI  - Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis.
AB  - Regulatory T cells (Treg) are a CD4(+) lymphocyte subset involved in self
      tolerance and autoimmunity prevention. There is evidence for a phenotypic and/or
      functional impairment of this cell subset during the natural history of several
      chronic autoimmune/inflammatory diseases, including rheumatoid arthritis (RA).
      Although the intracellular transcription factor FoxP3 is thought to be the master
      regulator of Treg cell function, a number of other molecules expressed on the
      cell surface have been proposed for the identification of Treg cells. This is
      important in order to favour their possible selective isolation and in the
      development of new therapeutic strategies. In the present paper, available data
      on phenotypic and functional characterization of Treg cells in both peripheral
      blood and synovial fluid from RA patients are reviewed and their possible
      pathogenic role in triggering and perpetuating rheumatoid joint inflammation is
      discussed. 

PMID- 26000108
TI  - Adult-onset Still disease: a rare disorder with a potentially fatal outcome.
AB  - PURPOSE: The aim of this study was to assess the clinical and laboratory features
      of a cohort of Italian patients with adult-onset Still disease (AOSD) with
      particular attention on possible life-threatening complications. METHODS: The
      clinical charts of 41 consecutive Italian patients with AOSD referred to our
      rheumatological department over the last 10 years were retrospectively examined.
      Data regarding clinical manifestations, laboratory features and complications
      were collected and compared with those reported in literature. RESULTS: The most
      frequent manifestations were: fever (90.2%), arthralgias (80.4%), skin rash
      (75.6%), sore throat (53.6%), arthritis (51.2%), lymphadenopathy (48.7%),
      hepatosplenomegaly (41.4%), myalgia (21.9%), fatigue (12%), diarrhoea and
      vomiting (9.7%), pleural effusion (9.7%), pericardial effusion (4.8%) and
      abdominal pain (2.4%). In two patients whose cases are described in detail; the
      course of the disease was complicated by disseminated intravascular coagulopathy,
      in one patient with a fatal outcome. ESR, CRP and leucocyte count mean values
      were 69.41 mm/h, 69.05 mg/l and 18,798.5 cell/mm(3) (neutrophils 84.64%),
      respectively. Serum ferritin levels were increased in 48.7% of patients while
      transaminases were elevated in 42.6% of patients (71% considering only patients
      in an active phase of disease). CONCLUSION: The results of this study are in line
      with those reported for other cohorts of patients. Even if the prognosis of AOSD
      is considered favourable, the present study indicates that the disease is a
      troubling condition needing prompt intervention. Occasionally, AOSD may rapidly
      worsen with life-threatening events.

PMID- 26000109
TI  - Protective molecules and their cognate antibodies: new players in autoimmunity.
AB  - Impairment of the clearance of apoptotic material seems to contribute to
      autoantigen exposure, which can initiate or maintain an autoimmune response in
      predisposed individuals. Complement component C1q, Creactive protein (CRP), serum
      amyloid P (SAP), mannose-binding lectin (MBL), apolipoprotein A-1 (Apo A-1) and
      long pentraxin 3 (PTX3) are molecules involved in the removal of apoptotic bodies
      and pathogens, and in other antiinflammatory pathways. For this reason they have
      been called "protective" molecules. C1q has a key role in the activation of the
      complement cascade and acts as a bridging molecule between apoptotic bodies and
      macrophages favouring phagocytosis. In addition to other functions, CRP, SAP and
      MBL bind to the surface of numerous pathogens as well as cellular debris and
      activate the complement cascade, thus stimulating their clearance by immune
      cells. The role of PTX3 is more controversial. In fact, PTX also promotes the
      clearance of microorganisms, but the activation of the complement cascade through
      C1q and removal of apoptotic material can be either stimulated or inhibited by
      this molecule. Antibodies against protective molecules have been recently
      reported in systemic lupus erythematosus and other autoimmune rheumatic diseases.
      Some of them seem to be pathogenetic and others protective. Thus, protective
      molecules and their cognate antibodies may constitute a regulatory network
      involved in autoimmunity. Dysregulation of this system might contribute to the
      development of autoimmune diseases in predisposed individuals. 

PMID- 26000111
TI  - Diagnostic sensitivity of thyroid autoantibodies assessed in a population-based,
      cross-sectional study in adults.
AB  - The aim of this study was to estimate the diagnostic sensitivity of thyroid
      autoantibodies in individuals with a case-mix of subjects with thyroid disease
      representing that of the general population. We measured thyroid microsome (TMA),
      thyroid peroxidase (TPO), thyroglobulin (TGA) and thyroid-stimulating hormone
      (TSH) receptor (TRA) autoantibodies in subjects in the bottom (hyperthyroid end)
      and top (hypothyroid end) four percentiles of the TSH distribution from among
      participants in a population-based survey of individuals aged >=40 years (the
      Cremona Study). TMA and TPO were the most sensitive autoantibodies in subjects in
      both the bottom percentiles (19.8% and 18.5%, respectively) and the top
      percentiles (51.2% and 53.8%, respectively) of the TSH distribution. TMA and TPO
      showed good agreement (kappa statistics 87.8%, 95% CI 80.1-95.5%) at both ends of
      the TSH distribution. TGA were the next most sensitive marker, although seldom
      detected if TMA or TPO were not present. TRA were detected only at the extremes
      of the TSH distribution (1st percentile, 31.8%; 100th percentile, 25.0%). We
      conclude that, among a case-mix of individuals with thyroid disease representing
      that of the general population, TMA and TPO are the most sensitive markers of
      thyroid disease. TGA only marginally increased the diagnostic sensitivity of TMA
      and TPO. TRA are sensitive markers of thyroid disease only at the extremes of
      thyroid function. 

PMID- 26000110
TI  - The soluble CTLA-4 receptor and its role in autoimmune diseases: an update.
AB  - CTLA-4, initially described as a membranebound molecule, is a costimulatory
      receptor transducing a potent inhibitory signal. Increasing evidence shows the
      CTLA-4 gene to be an important susceptibility locus for autoimmune
      endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T
      lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to
      possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA
      4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are
      detected in normal human serum, increased serum levels are observed in several
      autoimmune diseases (e.g. Graves' disease, myasthenia gravis, systemic lupus
      erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune
      pancreatitis and primary biliary cirrhosis). The biological significance of
      increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it
      can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by
      blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On
      the other hand, higher levels of sCTLA-4 could compete for the binding of the
      membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte
      activation, causing a reduction in inhibitory signalling. This double-edged
      nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in
      different outcomes during the clinical course of an autoimmune disease. 

PMID- 26000113
TI  - Accuracy of receptor-based methods for detection of thyrotropin-receptor
      autoantibodies: a new automated third-generation immunoassay shows higher
      analytical and clinical sensitivity for the differential diagnosis of
      hyperthyroidism.
AB  - PURPOSE: Specific autoantibodies acting as TSH receptor agonists (TRAb) are
      responsible for Graves' disease (GD). In the last 30 years three generations of
      assay methods for the detection of TRAb have become available. The aim of this
      multicentre study was to evaluate the analytical sensitivity, precision and
      diagnostic accuracy of TRAb measurement using a new automated assay in comparison
      with a second-generation standard method. METHODS: Serum samples from patients
      with GD (n=82), autoimmune thyroiditis (AIT, n=57) or hyperthyroidism (HT,
      n=292), from 106 healthy subjects and from 57 patients with infectious diseases
      were analysed using a third-generation TRAb immunoassay (anti-TSHR, RAD 120;
      Radim, Italy) based on the human monoclonal TSH receptor antibody M22. RESULTS:
      Using a cut-off value of 1.25 mIU/l, established by ROC curve analysis, 80/82 GD
      patients (97.5%), 68/292 HT patients (23.2%), and 6/57 AIT patients (10.5%) were
      TRAb-positive with the M22-based automated assay. The percentages of TRAb
      positivity were lower in the same patients when the measurements were done with
      the second-generation method (95.1%, 18.9%, 7.0%, respectively). CONCLUSION: The
      M22-based automated immunoassay shows high functional sensitivity (0.4 mIU/l) and
      high diagnostic specificity, is more sensitive than the standard second
      generation method and is less time-consuming and labourintensive, and is
      therefore the up-to-date technology for TRAb detection in clinical practice.

PMID- 26000112
TI  - Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow
      up of patients with rheumatoid arthritis treated with rituximab.
AB  - Rheumatoid arthritis (RA) is characterized by the presence of circulating
      rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA), which are
      positive in about 70-80% of patients. APCA have a higher specificity and
      therefore a higher diagnostic power than RF, but are less informative than RF in
      monitoring the course of the disease in patients under treatment. Recently, it
      has been reported that the anticitrullinated vimentin (a-MCV) antibody test can
      identify a particular subgroup of APCA that may be negative for anticyclic
      citrullinated peptide (a-CCP) antibodies. Concerning RF, the RF IgA isotype has
      been described as a more specific marker of erosive joint damage than total RF.
      The aim of our study was to monitor the levels of a-CCP, a-MCV, total RF and RF
      IgA in the follow-up of patients with RA treated with B-lymphocytedepletive
      rituximab (RTX), to detect any differences or peculiarities in patterns of these
      autoantibodies, especially in relation to their potential use as predictive
      markers of therapeutic response. We studied 30 patients with RA treated with RTX.
      All patients were previously unresponsive to at least 6 months of therapy with
      disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide,
      cyclosporine, chloroquine) and/or at least 6 months of therapy with anti-TNF
      biologics. The evaluation of response to RTX was made at month +6 using the EULAR
      criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline
      (before the first infusion of RTX) and after 1, 3 and 6 months. In serum samples
      obtained before treatment two cytokines essential for Blymphocyte proliferation,
      interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In
      all patients a significant and consistent reduction in all the tested antibodies
      was found during follow-up, with no differences in respect of the degree of
      response to RTX. Of note, at baseline, generally a higher titre of all
      autoantibodies was seen in patients who then showed a better response to RTX.
      Finally, there were no differences in serum concentrations of IL-6 and BLyS in
      patients in relation to the presence or absence of the autoantibodies
      investigated, nor was there any significant correlation between the serum
      concentrations of the cytokines and the titres of the autoantibodies. Thus,
      neither a-MCV compared to a- CCP, nor RF IgA compared to routine total RF,
      provided any additional predictive information in the follow-up of patients with
      RA treated with RTX. 

PMID- 26000114
TI  - Pearls in autoimmunity.
AB  - This manuscript does a review of the more frequent issues published at
      Autoimmunity Reviews, Journal of Autoimmunity and Autoimmunity in the period of
      January-December 2009. The following topics were commented: (1) multiple
      sclerosis (MS) and its relationships with Epstein Barr infection, with vitamin D
      polymorphism and the new modalities of MS treatment. (2) Type 1 diabetes and
      genetic discovers, studies with GAD 65 and IA-2 autoantigen and the association
      T1D and autoimmune organ-specific diseases. (3) Autoimmune thyroid disorders and
      its association with susceptibility genes and polymorphisms. (4) Multiplex
      autoantibody profiling approaches in MS and rheumatoid arthritis. (5) Th17
      cytokine in primary biliary cirrhosis, experimental autoimmune encephalomyelitis
      and celiac disease. (6) Vitamin D and experimental autoimmune prostatitis and
      pulmonary alveolar proteinosis. 

PMID- 26000116
TI  - Fetomaternal alloimmunity as a cause of liver disease.
AB  - Fetomaternal alloimmune disease has traditionally been associated with
      haematological disease such as fetomaternal alloimmune thrombocytopaenia and Rh
      haemolytic anaemia, but is now known to also be organ specific. Alloimmune
      membranous glomerulonephritis (AMG) is one of the most well understood organ
      specific alloimmune diseases. Neonatal haemochromatosis (NH) is a rare condition
      characterised by early liver failure in infants, with evidence suggesting that it
      is also alloimmune. Both AMG and NH appear to involve the passive transfer of
      alloantibodies to the fetus, which bind a specific alloantigen, fix complement
      and activate the terminal complement cascade. Although differences between AMG
      and NH are known, and evidence of the presence of antigen-specific alloantibodies
      in NH is still missing, we will use AMG as an example of fetomaternal organ
      specific alloimmune disease, and critically compare this to other emerging
      evidence that indicates that NH is also alloimmune. 

PMID- 26000115
TI  - Myositis-specific autoantibodies: detection and clinical associations.
AB  - In recent years, the detection and characterization of (novel) autoantibodies is
      becoming increasingly important for the early diagnosis of autoimmune diseases.
      The idiopathic inflammatory myopathies (IIM, also indicated with myositis) are a
      group of systemic autoimmune disorders that involve inflammation and weakness of
      skeletal muscles. One of the hallmarks is the infiltration of inflammatory cells
      in muscle tissues. A number of myositis-specific autoantibodies have been
      identified and these may be associated with distinct IIM subclasses and clinical
      symptoms. Here, we review all myositis-specific autoantibodies identified today
      as well as their target proteins, together with their clinical associations in
      IIM patients. Post-translational modifications that might be associated with the
      generation of autoantibodies and the development of the disease are discussed as
      well. In addition, we describe well established autoantibody detection techniques
      that are currently being used in diagnostic laboratories, as well as novel
      multiplexed methods. The latter techniques provide great opportunities for the
      simultaneous detection of distinct autoantibodies, but may also contribute to the
      identification of novel autoantibody profiles, which may have additional
      diagnostic and prognostic value. The ongoing characterization of novel
      autoantibody specificities emphasizes the complexity of processes involved in the
      development of such autoimmune diseases. 

PMID- 26000117
TI  - Prevalence of anti-histone antibodies, their clinical significance and
      correlation with other autoantibodies in a cohort of Italian scleroderma
      patients.
AB  - PURPOSE: The aim of our study was to determine the prevalence, clinical
      significance of antibodies to individual histone components and to evaluate their
      correlation with other autoantibody specificities in a cohort of Italian SSc
      patients. Some authors, demonstrated high prevalence of anti-histone antibodies
      in Italian SSc patients, associated with cardiac and renal involvement,
      suggesting a prognostic value of these autoantibodies; however, these data need
      to be confirmed. METHODS: Serum from 112 adult SSc patients, classified as
      diffuse (dc) and limited cutaneous (lc) SSc subsets were analyzed for
      autoantibodies by indirect immunofluorescence, fluoroenzyme immunoassay and
      enzyme immunoassay. RESULTS: AHA were found in 13 patients (11.6%), nine with
      lcSSc and four with dcSSc. Among them, five patients were anti-Scl70+ and four
      were anti-CENP B+. The presence of AHA was not associated with multi-organ
      involvement or with diffuse subset, as already described. Anti-Scl70 was detected
      in 43% of patients, anti-CENP B in 32% and anti-RNA polymerase III in 7.1%. We
      confirmed the association between anti-Scl70 antibodies and pulmonary fibrosis
      (OR 15.75, p < 0.0001). CONCLUSION: In our experience, the very low prevalence of
      AHA in Italian SSc patients and the lack of association with clinical
      manifestations suggest that this test is of little clinical use; however, it
      would be worthwhile extending the study to a larger population of patients.

PMID- 26000119
TI  - Toll-like receptors play a crucial part in the pathophysiological activity of
      antiphospholipid antibodies.
AB  - The antiphospholipid syndrome (APS) is a systemic autoimmune disease
      characterized by thrombosis, recurrent fetal loss and the presence of a variety
      of antiphospholipid antibodies (aPL), directed to phospholipids like Cardiolipin
      and phospholipid binding proteins like beta2-glycoprotein I. Till date, the
      pathophysiological processes underlying these thrombotic events were still not
      fully understood. Recent data support the idea that the aPL might act via
      enhanced cytokine release due to activation of certain Toll-like receptors. The
      investigation of some of those mechanisms in more detail enlightens the
      involvement of the intracellular receptors TLR7 and TLR8 in a central point.
      Using patients' IgG fractions and/or monoclonal aPL, either generated from mouse
      or from human B-cells for the stimulation experiments of monocytes, endothelial
      cells or dendritic cells, all these stimuli induced an enhanced expression and
      secretion of cytokines, especially TNFalpha, caused by specific regulation or
      activation of Toll-like receptors. Using specific agonists or inhibitors could
      confirm the causal connection of these stimulatory effects. This review focuses
      on the recent developments connecting the binding of aPL with the activity of
      Toll-like receptors, especially in monocytes, endothelial cells and dendritic
      cells. 

PMID- 26000120
TI  - MicroRNAs in autoimmune disease.
AB  - MicroRNAs (miRNAs) are non-coding, single-stranded small RNAs, usually 18-25
      nucleotides long, have ability to regulate gene expression post
      transcriptionally. miRNAs are highly homologous, conserved and are found in
      various living organisms including plants and animals. Present studies show that
      these small RNAs anticipate and are directly involved in many important
      physiological and pathological processes including growth, proliferation,
      maturation, metabolism, and inflammation among others. Evidences are accumulating
      that miRNAs play active role in directing immune responses and, therefore, might
      be involved in pathogenesis of autoimmune diseases. Recent studies have found
      that miRNAs are critical in proliferation, maturation and differentiation of T
      cells, B cells and, therefore, may affect the outcome of an immune response. In
      light of such understanding, this review briefly introduces miRNAs and discusses
      its role in the pathogenesis of various autoimmune diseases, as well as its
      potential as a biomarker and therapeutic target in the management of autoimmune
      diseases. 

PMID- 26000118
TI  - Pathophysiology of the antiphospholipid antibody syndrome.
AB  - Antiphospholipid antibodies (aPL) are associated with the recurrent pregnancy
      loss and thrombosis that characterizes the antiphospholipid antibody syndrome
      (APS). Although the ontogeny of these pathogenic antibodies has not been fully
      elucidated, there is evidence that indicates the involvement of both genetic and
      environmental factors. The ability of aPL to induce a procoagulant phenotype in
      APS patients plays a central role in the development of arterial and venous
      thrombotic manifestations typical of the disease. Inflammation serves as a
      necessary link between this procoagulant phenotype and actual thrombus
      development and is an important mediator of the placental injury seen in APS
      patients with obstetric complications. Recent evidence has indicated a role for
      abnormal cellular proliferation and differentiation in the pathophysiology of
      APS, especially in those patients with pregnancy morbidity and other more
      atypical manifestations that have no identifiable thrombotic cause. The interplay
      of genetic and environmental factors responsible for aPL development and the
      mechanisms by which these antibodies produce disease in APS patients is the focus
      of this review. 

PMID- 26000121
TI  - Assessment of a combination screening assay for celiac disease.
AB  - PURPOSE: A serological screening assay for celiac disease (CD), designed to
      simultaneously detect IgA and IgG anti-tissue transglutaminase (a-tTG) and IgA
      and IgG deamidated gliadin peptide antibodies (a-DGP), was recently developed. In
      this study, we establish the performance of this assay. METHODS: We enrolled 41
      CD patients and 18 CD patients on gluten-free diets. The diagnosis of CD was
      based on histological and serological criteria, including concomitant positive
      serology tests (a-tTG, IgA anti-endomysial antibodies). As control population, we
      enrolled 169 subjects: 145 disease controls and 24 blood donors. In all cases,
      serum samples were tested for: IgA a-tTG, IgG a-tTG, IgA a-DGP, IgG a-DGP, IgA
      anti-endomysial antibodies (EMA), IgA and IgG for a-tTG and a-DGP in a single
      assay. RESULTS: The new test, QUANTA Lite (TM) h-tTG/DGP Screen, detects all IgA
      and IgG antibodies against atTG and a-DGP present in a sample. In our study, the
      test showed 100% sensitivity and 91.12% specificity. CONCLUSIONS: This study
      showed additional value of the new h-tTG/DGP Screen assay, which proved superior
      to more conventional assays and can be considered the best initial test for CD.
      Further studies are necessary to determine whether combination of h-tTG/DGP
      Screen with IgA a-tTG or IgA a-DGP can be used to obviate the need for duodenal
      biopsy in high- and low-risk populations.

PMID- 26000123
TI  - Differentiation of autoimmune pancreatitis from pancreas cancer: utility of anti
      amylase and anti-carbonic anhydrase II autoantibodies.
AB  - PURPOSE: To investigate the utility of different combinations of serum anti
      carbonic anhydrase II antibodies (CA II Abs), anti-alpha amylase antibodies (AMY
      alpha Abs) and IgG4 levels for the diagnosis of autoimmune pancreatitis (AIP).
      METHODS: We recruited 93 patients with clinical suspicion for AIP and 94 patients
      as control groups between June 2003 and October 2009. Serum antibodies were
      measured using homemade enzyme linked immunosorbent assay and IgG4 levels were
      determined by nephelometry. RESULTS: Both CA-II Abs and AMY-alpha Abs had the
      highest sensitivity (83%) although AMY-alpha Abs (89%) were more specific than CA
      II Abs (75%). The presence of increased IgG4 levels was the most specific
      serological marker (94%), but it had the lowest sensitivity (58%). The
      combination of the three serological markers altogether had the highest
      specificity (99%) and positive predictive value (PPV) (86%), but they had a
      rather low sensitivity (50%). When we combined CA-II Abs and AMY-alpha Abs
      without IgG4 levels, we got the highest sensitivity (75%) and negative predictive
      value (98%) but the specificity and the PPV decreased to 93 and 50%,
      respectively. Importantly, AMY-alpha Abs were not detected in pancreas cancer.
      CONCLUSIONS: The presence of serum CA-II and AMY-alpha Abs with increased IgG4 is
      useful in the differential diagnosis of AIP from pancreatic cancer.

PMID- 26000124
TI  - In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and
      a human thyroid-blocking autoantibody (K1-70).
AB  - PURPOSE: To study in vivo effects of the human monoclonal TSH receptor (TSHR)
      autoantibodies M22 (stimulating type) and K1-70 (blocking type) on thyroid
      hormone levels in rats. METHODS: Serum levels of total T4, free T4, M22 and K1-70
      were measured following intramuscular injection of M22 IgG (2-4 MUg/animal), K1
      70 IgG (10-200 MUg/animal) or both into rats. Thyroid pathology was assessed in
      M22-injected rats. RESULTS: Serum levels of total T4 and free T4 increased in a
      dose-dependent manner following injection of M22 IgG. Thyroid follicular cell
      hypertrophy was dependent on the dose of M22 IgG. K1-70 IgG caused a dose
      dependent decrease of total T4 and free T4 levels in rats receiving K1-70 only.
      The stimulating effects of M22 IgG on T4 levels in rats were completely inhibited
      by K1-70 IgG. CONCLUSION: M22 is a potent stimulator of thyroid hormone secretion
      in vivo. In contrast, K1-70 inhibits thyroid hormone secretion in vivo.
      Furthermore, K1-70 has the ability to inhibit the stimulating activity of M22 in
      vivo and as such has potential as a new drug to block TSHR stimulation by
      autoantibodies in Graves' disease.

PMID- 26000122
TI  - Towards systemic sclerosis and away from primary biliary cirrhosis: the case of
      PTPN22.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease
      characterized by immune-mediated destruction of the small and medium size
      intrahepatic bile ducts. PBC patients often have concomitant autoimmune diseases,
      which are most often autoimmune thyroid disease, as well as Sicca syndrome.
      Occasionally, some PBC patients will also have systemic sclerosis of the limited
      cutaneous type (lcSSc). Conversely, up to one-fourth of SSc patients are positive
      for antimitochondrial antibody, the serologic hallmark of PBC. It is also common
      for SSc patients to have concomitant autoimmune disease, which may include PBC in
      rare cases. This has led to speculation of shared environmental and/or genetic
      factors, which lead to the development of PBC in SSc patients and vice versa.
      Recent genetic studies have revealed associations with several genes in both SSc
      and PBC. PTPN22 is one gene that has been associated with SSc, but not with PBC.
      It may be argued that some SSc patients with a particular genotype, which shares
      genes found in both conditions may develop PBC. Likewise, particular genes such
      as PTPN22 may infer susceptibility to SSc alone. The presence of PTPN22 may also
      contribute to the development of SSc in PBC patients. The lack of a large number
      of overlapping genes may, in part, explain the relative rarity of PBC with SSc
      and vice versa. This review will examine the literature surrounding the genetic
      associations of PBC and SSc, and the role of PTPN22 in particular. 

PMID- 26000125
TI  - Routine use of Zenit RA, a novel chemiluminescent immunoanalyzer in autoimmune
      disease diagnosis.
AB  - The detection of antibodies is useful to diagnose and/or to classify autoimmune
      diseases as connective tissue diseases and vasculitis. Zenit RA is a fully
      automated immunoanalyzer. The aim of this study was to compare the predictive and
      discriminative performance of the Zenit RA anti-cyclic citrullinated peptide
      (CCP), anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (aB2GP1) tests to
      conventional ELISAs on clinically well-defined groups of patients and to daily
      evaluate the determination of anti-extractable nuclear antigen (ENA), anti-double
      stranded DNA (dsDNA), anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3)
      antibodies in a hospital laboratory. Reagents available on Zenit RA analyzer
      exhibit good diagnostic performances, regarding sensitivity, specificity,
      positive and negative predictive values. Global agreements between Zenit RA and
      conventional tests were from 90 to 98 % (Kappa-values ranging 0.56-0.94): 96 %
      for anti-CCP, 90-94 % for aCL and aB2GP1, 94 % for anti-dsDNA, 97 % for anti-ENA,
      98 % for anti-MPO and 95 % for anti-PR3 antibodies. Zenit RA analyzer is easy to
      rapidly detect the most common autoantibodies in autoimmune diseases. This system
      has a potential to provide clinically useful data within a short time. Because of
      the flexibility of its work modalities, it is well adapted to determine antigenic
      specificities in daily practice. 

PMID- 26000126
TI  - Missing links in high quality diagnostics of inflammatory systemic rheumatic
      diseases: It is all about the patient!
AB  - The aim of this review is to focus attention on high quality diagnostics of
      systemic inflammatory rheumatic diseases. Though many steps in the diagnostic
      process from the first visit in a doctor's office till a final diagnosis have
      been established a lot of things still must be done to improve quality assurance
      and secure fast and safe transmission of data from one step to the next. Some
      procedures inherent in early high quality diagnostics need to be worked out. A
      number of elements can be improved, some stumble stones can be removed, and a
      tighter collaboration between actors at different levels in the line of action in
      clinical and laboratory medicine can be organized. Several proposals have been
      made by international working groups such as the IUIS International Autoantibody
      Standardization Committee, and the EASI steering group in collaboration with
      their national EASI teams. Practical exercises carried out for more than three
      decades by the European Consensus Finding Study Group have proven to very useful.
      The review points at several principles worked out by these international expert
      groups can be useful in actual daily practice also in rheumatology. The hope is
      that the presentation will give rise to a continued discussion on how to link
      different parts of the diagnostic process together and strengthen collaboration
      between all teams involved in the diagnostic chain. The ultimate measure of
      success will be better clinical outcomes for patients and increased satisfaction
      in their families. 

PMID- 26000128
TI  - Automation in indirect immunofluorescence testing: a new step in the evolution of
      the autoimmunology laboratory.
AB  - Indirect immunofluorescence (IIF) plays an important role in immunological and
      immunometric assays for detecting and measuring autoantibodies. This technology
      was the first multiplex method used to detect cardinal autoantibodies for the
      diagnosis of autoimmune diseases. Over the last 20 years, research has enabled
      the progressive identification of cell and tissue autoantigens which are the
      target of autoantibodies originally detected by IIF. Accordingly, newer
      immunometric methods, capable of measuring concentrations of specific
      autoantibodies directed against these autoantigens, allowed for a gradual
      replacement of the IIF method in the autoimmunology laboratory. Currently, IIF
      remains the method of choice only in selected fields of autoimmune diagnostics.
      Following the recent statement by the American College of Rheumatology that the
      IIF technique should be considered as the standard screening method for the
      detection of ANA, the biomedical industry has developed technological solutions
      which significantly improve automation of the procedure, not only in the
      preparation of substrates and slides, but also in microscope reading. This review
      summarizes the general and specific features of new available commercial systems
      (Aklides, Medipan; Nova View, Inova; Zenit G Sight, A. Menarini Diagnostics;
      Europattern, Euroimmun; Helios, Aesku.Diagnostics; Image Navigator, Immuno
      Concepts; Cytospot, Autoimmun Diagnostika) for automation of the IIF method. The
      expected advantages of automated IIF are the reduction in frequency of false
      negative and false positive results, the reduction of intra- and inter-laboratory
      variability, the improvement of correlation of staining patterns with
      corresponding autoantibody reactivities, and higher throughput in the laboratory
      workflow. 

PMID- 26000130
TI  - Characterization for anti-cytoplasmic antibodies specificity by morphological and
      molecular techniques.
AB  - PURPOSE: The aim of our study was the characterization of anti-cytoplasmic
      antibodies by home-made morphological and biochemical techniques. Indeed,
      indirect immunofluorescence (IIF) on HEp-2 cell line is not always exhaustive in
      relation to the complexity of the antigens involved. METHODS: Nine serum samples
      with anti-cytoplasmic antibodies (2 anti-Golgi apparatus, 3 with diffuse pattern
      and 4 with lysosome/endosome-like pattern) were tested with fluorescent confocal
      microscopy, Western blot analysis and, when necessary, with electron microscopy
      technique. RESULTS: Confirmation of the IIF staining pattern was performed in
      confocal microscopy by comparison with the respective antibody marker. The anti
      endoplasmatic reticulum positivity was also confirmed by electron microscopy
      evaluation. Both anti-lysosome/endosome and anti-endoplasmatic reticulum
      positivity have been definitely identified by Western blot through clear
      reactivity with calreticulin and LC3B, respectively. CONCLUSIONS: These results
      do not aim at representing a standard routine laboratory procedure. Electron
      microscopy evaluation cannot be proposed as a routine approach, but confocal
      microscopy technique may be offered in centralized reference laboratories. Newer
      technologies, especially multiplex immunoassay, can also lead to an easier
      identification of these autoantibodies, without recurring to a home-made
      immunoblotting. Only with a complete characterization we will be able to define
      the clinical relevance of anti-cytoplasmic antibodies, which are still considered
      as "esoteric" and not as "diagnostic" antibodies.

PMID- 26000127
TI  - Toward a new autoantibody diagnostic orthodoxy: understanding the bad, good and
      indifferent.
AB  - Rapid advances in diagnostic technologies used to detect autoantibodies have made
      it difficult for even the most modern laboratory to keep abreast of the changing
      approaches and platforms, not to mention the clinicians who are hard pressed to
      keep abreast of evolving diagnostic paradigms attended by these newer techniques.
      While autoantibody testing is traditionally considered to be primarily serving
      the realm of diagnostic medicine, there is little doubt that autoantibodies are
      also being recognized as an approach to providing prognostic and therapeutic
      information. Accordingly, along with related proteomics, genomics and
      metabolomics, it is taking on increasing importance in the realm of personalized
      medicine. In today's world of autoantibody diagnostics, overarching concerns
      about false-negative and false-positive autoantibodies tests cannot be summarily
      dismissed by citing pros or cons of any one technology or diagnostic platform,
      but often point to persisting gaps in our knowledge about, and understanding of,
      the origin and roles of autoantibodies. Before we can hope to completely
      understand the enigmas that attend the results of autoantibody diagnostic tests,
      perhaps it is time to step back and re-examine long-accepted paradigms and
      beliefs. This review will address some of the issues that impact on autoantibody
      detection technologies and some of the considerations and issues that will attend
      a new orthodoxy of autoantibody diagnostics. These issues will be addressed in
      the context of "bad" (pathogenic), "good" (protective) or "indifferent" (no
      apparent role in disease) autoantibodies. 

PMID- 26000129
TI  - The immunofluorescence techniques in the diagnosis of endocrine autoimmune
      diseases.
AB  - In the study of autoimmune diseases, the laboratory plays a very important role.
      We describe the immunofluorescence techniques (direct, indirect, complement
      fixing, double) for determining the presence of autoantibodies and their role in
      the autoimmune endocrine diseases. 

PMID- 26000132
TI  - Popular and unpopular infectious agents linked to primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease
      characterized by the autoimmune destruction of the biliary epithelial cells of
      the small and medium-size bile ducts. The disease affects middle aged women and
      usually affects more than one member within a family. The pathognomonic
      serological hallmark of the disease is the presence of circulating anti
      mitochondrial antibodies, and disease-specific anti-nuclear antibodies.
      Susceptibility genes and environmental risk factors such as infections and
      smoking have been reported as important for the development of the disease. Among
      the environmental agents, infectious triggers are the best studied. Most of the
      work published so far has investigated the role of infections caused by
      Novosphingobium aromaticivorans and Escherichia coli. This review will discuss
      the popular and unpopular infectious agents causatively linked to PBC. It will
      also examine reports investigating the epidemiological aspects of the disease and
      their direct or indirect implications to bacterial-induced PBC. 

PMID- 26000131
TI  - The immunopathogenetic role of autoantibodies in canine autoimmune hepatitis:
      lessons to learn from human autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is not a disease entity restricted to man, but it can
      be found in other animals including canines. An increasing number of studies have
      focused on the immunopathogenesis of human autoimmune hepatitis (hAIH), but
      little is known of what triggers canine autoimmune hepatitis (cAIH). Several
      drugs, toxins, microbial and viral agents are able to induce autoantibodies and
      indeed immune-mediated chronic canine hepatitis with immunological and
      serological features similar of those seen in the human disease. We discuss the
      features of cAIH paying attention to the autoantibody profile of the disease in
      comparison to that seen in hAIH. We also discuss the immunomodulatory role of
      specific molecular signaling pathways such as those mediated by tumor growth
      factor and p38 mitogen-activated kinase in the induction of AIH, and the
      potential of these molecules to act as targets of specialized immunotherapeutic
      interventions. Review of the literature indicates that we have more to learn for
      the delineation of autoantibody profile and the antigen-specific immunoregulatory
      mechanisms involved in the pathogenesis of cAIH from the human disease, rather
      than the other way around. 

PMID- 26000134
TI  - Recurrence of autoimmune liver diseases after liver transplantation: clinical
      aspects.
AB  - Autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing
      cholangitis are autoimmune liver diseases characterized by progressive immune
      mediated inflammation leading to the destruction of the hepatocytes and the
      biliary epithelial cells, and eventually to cirrhosis and liver failure. The
      ultimate treatment of these diseases, upon the establishment of end-stage liver
      disease, includes liver transplantation (LT). Recurrence of autoimmune liver
      diseases after LT is an entity increasingly recognized in the last few decades.
      The mechanisms driving recurrence remain poorly understood. The accurate
      diagnosis of the recurrence and the proper management of the affected patients
      remains a clinical challenge. This review discusses clinical aspects related to
      the recurrence of autoimmune liver diseases after LT. The main goals of this
      review are to discuss the reasons explaining the variability of the incidence
      rates of recurrent autoimmune disease and the outcome and risk factors for
      recurrent disease. We discuss in detail the diagnostic criteria and the treatment
      options of these disorders. 

PMID- 26000133
TI  - Predicting and preventing autoimmunity: the case of anti-mitochondrial
      antibodies.
AB  - To be able to predict who will develop autoimmune disease would allow for early
      treatment which may dramatically alter the course of the disease. In some cases,
      it may also lead to prevention of the disease development. The prediction of
      disease development is based on the analysis of risk factors which have been
      associated with the disease in question. These factors include genetic
      susceptibility, as well as immunological and environmental factors. One
      autoimmune disease that may serve as a model for disease prediction is primary
      biliary cirrhosis (PBC), an autoimmune liver disease affecting the small- and
      medium-sized bile ducts. PBC could be an ideal model due to recent advances in
      elucidating its genetic associations. As well, a variety of immunological and
      environmental risk factors have been well established. Indeed, the presence of
      PBC-specific antimitochondrial antibodies and/or antinuclear antibodies has been
      shown to be predictor of disease development and possibly prognosis. This review
      will examine the current evidence which suggests that we may potentially be able
      to predict the development of PBC in some individuals. These concepts may also be
      applied to autoimmune diseases in general. 

PMID- 26000135
TI  - Asialoglycoprotein receptor (ASGPR): a peculiar target of liver-specific
      autoimmunity.
AB  - Asialoglycoprotein receptor (ASGPR) autoantibodies have been considered specific
      markers of autoimmune hepatitis (AIH). The exact mechanisms responsible for the
      development of these autoantibodies and leading to autoimmunity to this peculiar
      liver receptor remain elusive. Furthermore, loss of T cell tolerance to ASGPR has
      been demonstrated in patients with AIH, but it is poorly understood whether such
      liver-specific T cell responses bear a pathogenic potential and/or participate in
      the precipitation of AIH. Newly developed enzyme-linked immunosorbent assays have
      led to the investigation of the sensitivity and specificity of anti-ASGPR
      antibodies for AIH. The present review provides an overview of the diagnostic and
      clinical relevance of anti-ASGPR antibodies. A thorough investigation of the
      autoreactivity against ASGPR may assist efforts to understand liver autoimmunity
      in susceptible individuals. 

PMID- 26000136
TI  - The X-factor in primary biliary cirrhosis: monosomy X and xenobiotics.
AB  - Primary biliary cirrhosis (PBC) is a chronic, cholestatic, autoimmune liver
      disease characterised by the destruction of small- and medium-sized bile ducts.
      The serological hallmark of PBC includes antimitochondrial antibodies (AMA). The
      disease has a striking female predominance, and primarily affects women of middle
      age. First-degree relatives, and in particular female relatives, are known to
      have an increased risk of developing the disease. Several studies have attempted
      to explain the female predominance of PBC, and autoimmune diseases in general.
      Two components that are of interest in PBC include monosomy X and xenobiotics.
      Monosomy X has been noted to be prevalent in the peripheral blood mononuclear
      cells of PBC patients. Xenobiotics, which are exogenous chemicals not normally
      found within the body, have been implicated in the modification of, and loss of,
      tolerance to AMA. Several cosmetics are known to contain these xenobiotics, which
      is of interest given the information provided in regards to known risk factors
      for PBC development. This review will focus on X monosomy and xenobiotics, which
      appear to constitute the X-factor of PBC. 

PMID- 26000137
TI  - Hair dyes as a risk for autoimmunity: from systemic lupus erythematosus to
      primary biliary cirrhosis.
AB  - Environmental and genetic factors appear to be involved in the pathogenesis of
      primary biliary cirrhosis (PBC), a chronic cholestatic liver disease
      characterized by immune-mediated destruction of the small and medium sized
      intrahepatic bile ducts. Environmental factors include exposure to various
      infectious, xenobiotic and chemical compounds. These exposures may occur
      occupationally, through water or air contamination, pharmacological
      administration or by elective exposure, to name a few. Hair dyes are compounds
      that have been implicated in the development of several autoimmune diseases,
      including systemic lupus erythematosus (SLE) and PBC. So far, only
      epidemiological studies have addressed the role of hair dyes in PBC, with limited
      results. Hair dyes in SLE have been examined, and have recently demonstrated an
      association, both epidemiologically and immunologically. This follows a series of
      negative studies, which may not have taken into account several features of hair
      dye use. This review will examine the literature surrounding hair dye use and
      SLE, and compare this to data surrounding PBC. Treating physicians should be
      prepared for questions surrounding the need to take precautions against repeated
      hair dye use and this topic is discussed further. 

PMID- 26000139
TI  - Phosphatidylserine-dependent anti-prothrombin antibodies (aPS/PT) in infliximab
      treated patients with inflammatory bowel diseases.
AB  - PURPOSE: To (1) examine the occurrence and concentrations of aPS/PT and aPL in
      inflammatory bowel disease (IBD) patients at the beginning of and during anti-TNF
      alpha therapy with infliximab; (2) investigate the link of the aPS/PT and aPL
      presence with antibodies to infliximab (ATI) formation; and (3) examine possible
      clinical consequences of aPS/PT and/or aPL positivity in IBD patients. MATERIALS
      AND METHODS: Thirty (30) IBD patients treated with infliximab were analyzed
      regarding aPS/PT, aPL, and ATI antibody serum levels by standardized ELISAs at
      treatment weeks 2 (W2) and 14 (W14). RESULTS: At W2, 40 % of infliximab-treated
      patients had elevated aPS/PT and 16.7 % had elevated aPL serum levels. At W14,
      the proportion of aPS/PT-positive sera decreased to 16.6 %, whereas aPL
      distribution remained unchanged. Moreover, concentrations of aPS/PT have shown
      significant differences at W2 (16.64 [10.06; 33.06] U for IgG and 18.46 [9.18;
      32.48] U for IgM) and at W14 (8.24 [2.78; 19.82] U for IgG and 8.57 [5.55; 26.82]
      U for IgM), p = 0.009 and p = 0.003, respectively. In ATI-positive samples,
      aPS/PT IgG were more frequent (p = 0.001 for W2 and p = 0.003 for W14), whereas
      aPS/PT IgM and aPL IgG/IgM did not show such association. CONCLUSIONS: Higher
      concentrations of aPS/PT IgG and IgM were found in IBD patients at the beginning
      of the biological treatment period compared to the maintenance treatment period.
      Moreover, aPS/PT IgG were more frequent in ATI-positive individuals, which was
      not observed in aPL. We speculate that there is a relationship between the aPS/PT
      and the severity of inflammation and auto-aggressive processes in IBD.

PMID- 26000138
TI  - Blocking type TSH receptor antibodies.
AB  - TSH receptor (TSHR) autoantibodies (TRAbs) play a key role in the pathogenesis of
      Graves' disease. In the majority of patients, TRAbs stimulate thyroid hormone
      synthesis via activation of the TSHR (stimulating TRAbs, TSHR agonists). In some
      patients, TRAbs bind to the receptor but do not cause activation (blocking TRAbs,
      TSHR antagonists). Isolation of human TSHR monoclonal antibodies (MAbs) with
      either stimulating (M22 and K1-18) or blocking activities (5C9 and K1-70) has
      been a major advance in studies on the TSHR. The binding characteristics of the
      blocking MAbs, their interaction with the TSHR and their effect on TSHR
      constitutive activity are summarised in this review. In addition, the binding
      arrangement in the crystal structures of the TSHR in complex with the blocking
      MAb K1-70 and with the stimulating MAb M22 (2.55 A and 1.9 A resolution,
      respectively) are compared. The stimulating effect of M22 and the inhibiting
      effect of K1-70 on thyroid hormone secretion in vivo is discussed. Furthermore
      the ability of K1-70 to inhibit the thyroid stimulating activity of M22 in vivo
      is shown. Human MAbs which act as TSHR antagonists are potentially important new
      therapeutics. For example, in Graves' disease, K1-70 may well be effective in
      controlling hyperthyroidism and the eye signs caused by stimulating TRAb. In
      addition, hyperthyroidism caused by autonomous TSH secretion should be treatable
      by K1-70, and 5C9 has the potential to control hyperthyroidism associated with
      TSHR activating mutations. Furthermore, K1-70 has potential applications in
      thyroid imaging as well as targeted drug delivery to TSHR expressing tissues. 

PMID- 26000140
TI  - Autoimmunity in connection with a metal implant: a case of
      autoimmune/autoinflammatory syndrome induced by adjuvants.
AB  - Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been
      recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises
      several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome,
      silicosis and post-vaccination phenomena, autoimmunity related to infectious
      fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report
      the case of a 23-year-old woman who developed serial episodes of high fever,
      extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies,
      hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment
      abnormalities, elevated serum ferritin levels, and transient low positive
      antinuclear antibodies 1 year after she had a nickel-titanium chin implant for
      cosmetic reasons. The clinical picture simulated a variety of probable diseases:
      systemic lupus erythematosus, Kikuchi-Fujimoto syndrome, adult onset Still's
      disease, antiphospholipid syndrome, and hemophagocytic syndrome, among others, so
      she underwent an extensive medical investigation including two lymph node
      biopsies. She received treatment accordingly with steroids, methotrexate, and
      mofetil mycophenolate, with initial improvement of her symptoms, which recurred
      every time the dose was reduced. Two and a half years later the patient decided
      to retire the chin implant and afterwards all her systemic symptoms have
      disappeared. She remains in good health, without recurrence of any symptom and
      off medications until today. Albeit this patient fulfills proposed major ASIA
      criteria, to our knowledge it would be the first description of systemic features
      of autoinflammation in connection with a metal implant. 

PMID- 26000141
TI  - Digital ulcers secondary to Sneddon's syndrome successfully treated with
      Bosentan: not only useful in Systemic Sclerosis.

PMID- 26000143
TI  - Detection of autoantibodies in a point-of-care rheumatology setting.
AB  - Autoimmune rheumatic diseases are common and confront society with serious
      medical, social, and financial burdens imposed by their debilitating nature. Many
      autoimmune diseases are associated with a particular set of autoantibodies, which
      have emerged as highly useful to define and classify disease, predict flares, or
      monitor efficacy of therapy. However, current practice for monitoring
      autoantibodies is protracted, labor-intensive, and expensive. This review
      provides an overview on the value of point-of-care (POC) biosensor technology in
      the diagnosis and management of patients with autoimmune rheumatic diseases. Real
      time measurement of autoantibodies will clearly benefit the rheumatology practice
      in emergency and urgent care settings, where definitive diagnosis is essential
      for initiation of correct critical care therapy. Immediate serological
      information in clinic will provide considerable value for long-term patient care
      and an opportunity for an instant, result-deduced therapeutic action, avoiding
      delays and improving compliance, especially in field-based and remote areas. We
      describe the particular autoantibodies that are useful disease and activity
      markers and would, therefore, be attractive to POC applications. Already existing
      biosensors and platforms that show promise for autoantibody testing are
      summarized and comparatively evaluated. As POC assessment is gaining momentum in
      several areas of patient care, we propose that rheumatology is poised to benefit
      from this innovative and affordable technology. 

PMID- 26000144
TI  - Arterial occlusion mimicking vasculitis in a patient with incontinentia pigmenti.
AB  - A large number of diseases can mimic a vasculitis. The diagnosis can be
      challenging due to the similarity with several diseases that have a different
      pathogenesis. As reported in the literature, incontinentia pigmenti (IP), a rare
      genetic disorder, can present vascular alterations on eye, brain and lung. We
      report a case of peripheral arterial disease in a patient with IP, suggesting
      further vascular localizations of the disease. 

PMID- 26000142
TI  - Autoantibodies in liver disease: important clues for the diagnosis, disease
      activity and prognosis.
AB  - It has been well established that numerous kinds of autoantibodies have been
      detected in liver disease. Some kinds of autoantibodies may be helpful in the
      diagnosis of autoimmune liver diseases including autoimmune hepatitis, primary
      biliary cirrhosis or primary sclerosing cholangitis. However, these
      autoantibodies are present even in sera of patients with viral hepatitis, drug
      induced hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and
      hepatocelluar carcinoma as well as in sera of patients with autoimmune liver
      diseases. Other kinds of autoantibodies are recognized as predictive hallmarks
      for disease activity or prognosis in liver diseases. On the other hand, treatment
      with interferon initiates the production of several types of autoantibodies in
      patients with chronic hepatitis C virus infection. Some of autoantibodies induced
      by interferon may postulate the treatment outcome in those patients. Recent
      studies also revealed the close correlation between oxidative stress and the
      production of autoantibodies in liver diseases. This article primarily reviews
      the recent advances of autoantibodies in the liver diseases and discusses the
      clinical significance of these autoantibodies. 

PMID- 26000146
TI  - StreptInCor: a model of anti-Streptococcus pyogenes vaccine reviewed.
AB  - Streptococcus pyogenes infections remain a health problem in multiple countries
      because of poststreptococcal sequelae, such as rheumatic fever and rheumatic
      heart disease. The epidemiological growth of streptococcal diseases in
      undeveloped and developing countries has encouraged many groups to study vaccine
      candidates for preventing group A streptococcus infections. We developed a
      vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C
      terminal portion of the M protein that encompasses both T and B cell protective
      epitopes. Using human blood samples, we showed that the StreptInCor epitope is
      recognized by individuals bearing different HLA class II molecules and could be
      considered a universal vaccine epitope. In addition, the StreptInCor molecular
      structure was solved by nuclear magnetic resonance spectroscopy, and a series of
      structural stability experiments was performed to elucidate its folding/unfolding
      mechanism. Using BALB-c and HLA class II transgenic mice, we evaluated the immune
      response over an extended period and found that StreptInCor was able to induce a
      robust immune response in both models. No cross-reaction was observed against
      cardiac proteins. The safety of the vaccine epitope was evaluated by analyzing
      histopathology, and no autoimmune or pathological reactions were observed in the
      heart or other organs. Vaccinated BALB/c mice challenged with a virulent strain
      of S. pyogenes had 100 % survival over 30 days. Taking all results into account,
      StreptInCor could be a safe and effective vaccine against streptococcus-induced
      disease. 

PMID- 26000145
TI  - Natural killer cells in patients with severe chronic fatigue syndrome.
AB  - Maintenance of health and physiological homeostasis is a synergistic process
      involving tight regulation of proteins, transcription factors and other molecular
      processes. The immune system consists of innate and adaptive immune cells that
      are required to sustain immunity. The presence of pathogens and tumour cells
      activates innate immune cells, in particular Natural Killer (NK) cells.
      Stochastic expression of NK receptors activates either inhibitory or activating
      signals and results in cytokine production and activation of pathways that result
      in apoptosis of target cells. Thus, NK cells are a necessary component of the
      immunological process and aberrations in their functional processes, including
      equivocal levels of NK cells and cytotoxic activity pre-empts recurrent viral
      infections, autoimmune diseases and altered inflammatory responses. NK cells are
      implicated in a number of diseases including chronic fatigue syndrome (CFS). The
      purpose of this review is to highlight the different profiles of NK cells
      reported in CFS patients and to determine the extent of NK immune dysfunction in
      subtypes of CFS patients based on severity in symptoms. 

PMID- 26000147
TI  - Interleukin-1 associations in inflammatory bowel disease and the enteropathic
      seronegative spondylarthritis.
AB  - PURPOSE: This study aims to investigate any associations of the proinflammatory
      cytokine IL-1 in treated patients with inflammatory bowel disease (IBD) and the
      enteropathic seronegative spondylarthritis (eSpA). METHODS: Thirty-four patients
      with Crohn's disease (CD), 26 with ulcerative colitis (UC) and 14 patients with
      SpA participated in the study. Valid clinical indexes, CRP values and the
      endoscopic and histologic examination were used for the determination of disease
      activity. IL-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1Ra) were measured by
      ELISA. Nonparametric tests were used for continuous and categorical data.
      RESULTS: Enteropathic SpA diagnosed in 29.4 % CD and 30.8 % UC patients. Active
      disease had 58.8 % CD (aCD), 76.9 % UC and 50 % SpA patients. Active and inactive
      CD (iCD) significantly differ on IL-1alpha levels (11.2 vs. 3.9 pg/ml; p =
      0.034). Active and inactive UC significantly differ on IL-1beta (3.7 vs. 2.3
      pg/ml; p = 0.054) and IL-1Ra levels (15.9 vs. 12.7 pg/ml; p = 0.023). Active and
      inactive SpA (iSpA) significantly differ on IL-1Ra (16.9 vs. 14.8 pg/ml; p =
      0.033) and marginally on IL-1alpha levels (20 vs. 3.9 pg/ml; p = 0.06). Patients
      with aCD/ieSpA exhibited significant differences on IL-1alpha (p = 0.022)
      compared to those with iCD/ieSpA. CONCLUSIONS: IL-1alpha is associated with CD
      activity, while IL-1beta and IL-1Ra are associated with UC activity in treated
      patients with IBD. Prominent cytokine in SpAs seems to be IL-1alpha.

PMID- 26000148
TI  - Intravenous immunoglobulin therapy in vasculitic ulcers: a case of polyarteritis
      nodosa.
AB  - INTRODUCTION: Polyarteritis nodosa (PAN) is a systemic necrotizing medium-size
      vessel vasculitis with variable clinical manifestations. Diagnosis is confirmed
      by histology or angiography. The mainstay of treatment is corticosteroids alone
      or combined with cyclophosphamide (CYF). CASE REPORT: Seventy-one-year-old
      female, follow-up started in 1997 at the age of 56 for suspected relapsing
      febrile viral exanthema. Skin biopsy was performed and the diagnosis of
      lymphomatoid papulosis was made, with complete response to treatment with
      dapsone. In 2005, she presented with arthralgia, lower limb (LL) edema, livedo
      reticularis and elevated erythrocyte sedimentation rate (ESR). PAN was confirmed
      on histology and visceral angiography; antineutrophil cytoplasmic antibodies
      (ANCA) were negative. She responded to prednisolone but relapsed in 2006. Twelve
      cycles of CYF were administered, with clinical, angiographic and analytical
      improvement. In 2008, a new relapse occured with LL neuropathic pain and ESR
      elevation. Electromyogram (EMG) confirmed axonal sensory polyneuropathy (PNP).
      Azathioprine was started with a poor response. A second EMG, 12 months later in
      2009 still evidenced PNP, and nerve biopsy confirmed vasculitic neuropathy. In
      2010, she had ulcers in LL and iron-deficient anemia. She started intravenous
      immunoglobulin (IVIG) for six cycles, achieving ulcer healing, absence of pain,
      no anemia and ESR normalization. DISCUSSION: IVIG therapy has proven benefit in
      Kawasaki disease, also showing efficacy in refractory ANCA-associated vasculitis.
      In PAN, only very few case reports show benefit. In this case, IVIG therapy
      induced total remission of LL ulcers and PNP, suggesting that it may be useful in
      selected cases of refractory PAN.

PMID- 26000149
TI  - New insights into HLA class I association to Behcet's syndrome in Iranian Azari
      patients.
AB  - Behcet's syndrome (BS) is a chronic recurrent inflammatory disorder characterized
      by oral and genital ulcers and ocular inflammation. BS has a complex genetic
      etiology. To evaluate the influence of human leukocyte antigen (HLA) class I in
      BS susceptibility in Iranian Azari population, we studied 290 BS patients and 300
      healthy controls. As expected, a high frequency of HLA-B5 was found. Remarkably,
      HLA-B35 frequency was higher in the patient than control group, and the frequency
      of HLA-B51, HLA-B52, and HLA-BW4 was significantly elevated. Thus, HLA-B5 and HLA
      B35 seem to confer susceptibility to BD in Iranian Azari patients. 

PMID- 26000150
TI  - Treatment of the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is characterized by a combination of laboratory
      findings (i.e., the presence of at least one antiphospholipid antibody) and
      clinical manifestations (arterial and/or venous thrombosis, obstetrical
      complications). Long-term oral anticoagulant is recommended to prevent recurrence
      of both arterial and venous thrombosis, whereas (low molecular weight) heparin
      plus aspirin is the treatment of choice to prevent further obstetrical
      complications. In the rare case of catastrophic antiphospholipid syndrome,
      heparin plus high-dose corticosteroids plus plasma exchange is associated with
      the highest recovery rate. Some new, non-antithrombotic-based treatments of
      antiphospholipid syndrome with rituximab, autologous stem cell transplantation,
      or hydroxychloroquine are also reviewed. 

PMID- 26000151
TI  - Skin CD30(+) T cells and circulating levels of soluble CD30 are increased in
      patients with graft versus host disease.
AB  - OBJECTIVE: To determine serum soluble CD30 (sCD30) levels in patients with graft
      versus host disease (GVHD). METHODS: Serum soluble CD30 levels and IgE levels
      were assayed by a sensitive ELISA in 57 patients with bone marrow
      transplantation, and in 44 healthy controls. We analyzed the type of effector T
      cells in patients with GVHD. RESULTS: Serum levels of sCD30 and serum IgE levels
      were significantly higher (p values <0.05) in patients with acute and chronic
      GVHD than in healthy controls. We found that CD30(+) T-cells are present in the
      skin of patients with GVHD. CONCLUSION: These results suggest that serum sCD30
      levels may be helpful for the management of patients with bone marrow
      transplantation.

PMID- 26000152
TI  - The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications.
AB  - Psoriasis and psoriatic arthritis represent two paradigmatic conditions
      characterized by chronic inflammation and possibly autoimmunity, despite the
      absence of known serum autoantibodies. The two diseases, albeit strongly
      correlated from clinical, genetic, and epidemiogical standpoints, manifest
      significant differences in terms of etiology and pathogenetic mechanisms.
      Nonetheless, Th17 cells appear crucial to both diseases, and IL23 is the cytokine
      involved in determining the fate of naive CD4+ cells to differentiate into a
      pathogenic phenotype. This basic experimental observation led to a clear
      understanding of the immune dysfunction causing psoriasis and psoriatic arthritis
      but, more importantly, also led to new therapeutic approaches. In recent years,
      monoclonal antibodies directed to IL12/IL23 (ustekinumab) or IL17 (secukinumab,
      ixekizumab, brodalumab) are being investigated or have proven to be beneficial
      for patients with psoriatic disease, thus further supporting the view that Th17
      cells play a pivotal role in disease onset and perpetuation. These most recent
      reports indeed represent significant developments that may allow overcoming the
      TNFalpha pathway as the major therapeutic target in chronic inflammation. 

PMID- 26000153
TI  - A rare combination of type 3 autoimmune polyendocrine syndrome (APS-3) or
      multiple autoimmune syndrome (MAS-3).
AB  - CONTEXT: Type 3 autoimmune polyendocrine syndrome (APS-3) is defined by the
      presence of an autoimmune thyroid disease and another autoimmune illness,
      excluding Addison's disease; this is a frequent combination. CASE PRESENTATION:
      We report the case of a 55 years old female patient with APS-3, with seven
      clinical or latent autoimmune manifestations. At 49 years of age she was admitted
      at the General Hospital for leukopenia, weight loss, tremors, anxiety and
      diarrhea. The personal history revealed ulcerative colitis and, during the last
      year, episodes of fever with migrant arthralgia and cutaneous lesions. The
      patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic
      control, gastrointestinal and rheumatologic disorders with specific biochemical
      tests, imaging and endoscopic procedures. We concluded that the patient was
      affected by APS-3, characterized by the association of Graves' disease,
      autoimmune leukopenia, latent autoimmune diabetes of the adult (LADA), autoimmune
      gastritis, ulcerative colitis, Sjogren's and anti-phospholipid syndromes. The
      patient started low doses of corticosteroid drugs for leukopenia, underwent
      (131)I therapy for hyperthyroidism and later started substitutive thyroid therapy
      with l-thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and
      artificial tears for Sjogren's syndrome. CONCLUSIONS: In this article we report a
      complex case of APS-3, characterized by the association of seven different
      autoimmune diseases, which required a complex therapeutic strategy.

PMID- 26000155
TI  - Efficiency of a solid-phase chemiluminescence immunoassay for detection of
      antinuclear and cytoplasmic autoantibodies compared with gold standard
      immunoprecipitation.
AB  - PURPOSE: The aim of this study was to compare the degree of agreement of a novel
      Zenit RA chemiluminescent immunoassay (CLIA) from A. Menarini Diagnostics
      (Florence, Italy) and the gold standard immunoprecipitation assay to screen for
      the presence of specific anti-U1snRNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti
      Jo-1((his)tRNA-Synthetase) and anti-Scl-70(Topo I) antibodies. MATERIALS AND
      METHODS: We studied 114 sera, 98 from patients with well-defined autoimmune
      connective tissue diseases and 16 from blood donor volunteers. All samples were
      fully characterized using the new chemiluminescent immunoassay and
      immunoprecipitation. In addition, all the samples were analyzed by indirect
      immunofluorescence (IIF) and anti-Scl-70(Topo I) antibodies were analyzed by
      immunoblot (IB) assay. Discrepant samples were analyzed using a commercial dot
      blot technique (Recomline from Mikrogen). The simple Kappa coefficient was used
      to measure the level of agreement between the results of Zenit RA CLIA and the
      gold standard. RESULTS: The Kappa agreement between Zenit RA CLIA and gold
      standard immunoprecipitation, as well as IB and IIFassays for the presence of
      anti-Scl-70(Topo I)(0.948) was excellent. The concordance between Zenit RA CLIA
      and gold standard immunoprecipitation for the presence of anti-U1snRNP (0.883),
      anti-Ro/SS-A (0.878), anti-Jo-1((his)tRNA-Synthetase) (0.791) and anti-Sm (0.786)
      was good, and excellent when the cut-off was raised to 14 U/ml (arbitrary
      units/ml). Between Zenit RA CLIA and gold standard immunoprecipitation for the
      presence of anti-La/SS-B, the Kappa agreement had a value of 0.689, but this
      improved to 0.775 when the cut-off was raised to14 U/ml. Precision was good based
      on the evaluation of replicate samples. Inter-assay coefficient variation was
      lower than 3.4 % (CV in %) in all the kits and <1.2 % (CV in  %) for intra-assay
      measurements. CONCLUSION: Our findings show that Zenit RA CLIA was specific and
      sensitive to detect anti-U1snRNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Jo
      1((his)tRNA-Synthetase) and anti-Scl70(Topo I) autoantibodies. This simple, fast
      and precise method can be a suitable option to analyze these autoantibody
      specificities.

PMID- 26000154
TI  - Pathogenesis and potential therapeutic targets in systemic lupus erythematosus:
      from bench to bedside.
AB  - Systemic lupus erythematosus (SLE) is considered an autoimmune disease with
      multiorgan involvement. Many advances have been made during the last decade
      regarding inflammatory pathways, genetic and epigenetic alterations, adaptive and
      innate immune system mechanisms specifically involved in SLE pathogenesis.
      Apoptosis has been proposed as an important player in SLE pathogenesis more than
      a decade ago. However, only recently new key apoptotic pathways have been
      investigated and the link between apoptotic debris containing autoantigens,
      innate immunity and ongoing inflammation has been further elucidated. Better
      understanding of cellular mechanisms and involved cytokines contributed to the
      development of new biological drugs specifically addressed for SLE therapy. 

PMID- 26000157
TI  - The introduction of anti-phosphatidylserine/prothrombin autoantibodies in the
      laboratory diagnostic process of anti-phospholipid antibody syndrome: 6 months of
      observation.
AB  - PURPOSE: To evaluate the impact of the introduction of the anti
      phosphatidylserine/prothrombin autoantibodies (aPS/PT) in the laboratory
      diagnostic process of anti-phospholipid antibody syndrome (APS). METHODS: Four
      hundred and twenty-one patients (71.5 % females; 53 +/- 15 years) presenting a
      medical prescription for aPS/PT antibodies were consecutively enrolled in the
      study from March 2013 to August 2013. During the same period, aPS/PT were
      additionally investigated in a selected series of 62 patients characterized by
      difficult lupus anticoagulant (LA) tests interpretation and in a retrospective
      series of 52 LA positive cases with available data about anti-prothrombin (aPT)
      antibodies. The aPS/PT antibodies, as well as the anti-cardiolipin (aCL), the
      anti-beta2 glycoprotein I (abeta2GPI) and the aPT antibodies were analyzed by
      ELISA. LA was tested according to the recommended criteria, performing both the
      screen and the confirm steps. RESULTS: Overall, aPS/PT IgM positive (>30 U/ml)
      and/or IgG frankly positive (>40 U/ml) antibodies were found in 49/421 (11.6 %)
      cases. Among the LA positive patients, we found 56.1 % aPS/PT positive versus
      31.7 % aCL and/or abeta2GPI positive cases, with limited (17.1 %) simultaneous
      positivity. The PS/PT complex resulted the newly recognized specificity in about
      27 % of patients recruited from the subset with difficult LA test interpretation.
      Compared to aPT antibodies, the aPS/PT antibodies displayed a much higher
      sensitivity (55.8 versus 15.4 %) in LA positive patients. CONCLUSIONS: The
      introduction of aPS/PT antibodies in the diagnostic process of APS is highly
      recommended, since they disclose a notable diagnostic performance and a high
      correlation with LA activity, such that they can be a viable alternative.

PMID- 26000156
TI  - Celiac and non-celiac gluten sensitivity: a review on the association with
      schizophrenia and mood disorders.
AB  - An association between many psychiatric and gluten-related disorders has been
      known for some time. In the case of schizophrenia and mood disorders, the major
      psychiatric disorders, there is much evidence, not without contradictions, of a
      possible association between schizophrenia and celiac disease. The association
      between mood disorders and gluten-related disorders, especially celiac disease,
      has only been studied for depression, often coupled with anxiety, and very
      recently for bipolar disorder. Since non-celiac gluten sensitivity is now known
      to be different from celiac disease, many studies have shown that gluten
      sensitivity is also associated with major psychiatric disorders. Here we review
      the literature on the association between schizophrenia/mood disorders and celiac
      disease/gluten sensitivity, pointing out the differences between these
      associations. 

PMID- 26000158
TI  - Myositis autoantibodies and clinical phenotypes.
AB  - Autoantibodies are powerful diagnostic tools in idiopathic inflammatory
      myopathies, especially for confirming the diagnosis and contributing to the
      definition of disease subsets. They are present in over 80 % of patients with
      immuno-mediated myositis and directed towards ubiquitously expressed
      intracellular complexes. Most of these autoantibodies are reported also in other
      autoimmune diseases, while some are considered myositis-specific. Myositis
      autoantibodies are traditionally categorized in two groups, based on their
      diagnostic accuracy: myositis-specific antibodies (MSA) and myositis-associated
      antibodies (MAA), the latter mostly occurring in myositis-overlap syndromes.
      Besides the so-called traditional MSA, including anti-synthetases, anti-SRP and
      anti-Mi-2 antibodies, additional newly conceived immune targets have been
      recently identified, mostly in patients with severe forms of dermatomyositis or
      necrotizing myopathy. They mainly encompass enzymatic proteins essentially
      involved in the regulation of gene transcription or post-translational
      modifications, i.e., TIF1-gamma, NXP-2, MDA5, SAE and HMGCR. Among the MAA, anti
      PM/Scl and anti-Ku characterize an overlap polydermatomyositis/systemic sclerosis
      syndrome with severe interstitial lung involvement. 

PMID- 26000159
TI  - Muscle biopsy features of idiopathic inflammatory myopathies and differential
      diagnosis.
AB  - The gold standard to characterize idiopathic inflammatory myopathies is the
      morphological, immunohistochemical and immunopathological analysis of muscle
      biopsy. Mononuclear cell infiltrates and muscle fiber necrosis are commonly
      shared histopathological features. Inflammatory cells that surround, invade and
      destroy healthy muscle fibers expressing MHC class I antigen are the typical
      pathological finding of polymyositis. Perifascicular atrophy and microangiopathy
      strongly support a diagnosis of dermatomyositis. Randomly distributed necrotic
      muscle fibers without mononuclear cell infiltrates represent the
      histopathological hallmark of immune-mediated necrotizing myopathy; meanwhile,
      endomysial inflammation and muscle fiber degeneration are the two main
      pathological features in sporadic inclusion body myositis. A correct differential
      diagnosis requires immunopathological analysis of the muscle biopsy and has
      important clinical implications for therapeutic approach. In particular,
      unnecessary, potentially harmful, immune-suppressive therapy should be avoided
      alike in dystrophic myopathies with secondary inflammation. 

PMID- 26000160
TI  - Assessment of patients with idiopathic inflammatory myopathies and isolated
      creatin-kinase elevation.
AB  - Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by
      inflammation of the skeletal muscle. Weakness, mainly affecting the proximal
      muscles, is the cardinal muscular symptom in IIM. In patients with
      dermatomyositis, peculiar skin lesions are observed. The assessment of patients
      with IIM includes clinical and laboratory evaluation, and clinimetric
      measurements. Different tools have been proposed to measure muscular and
      extramuscular disease activity and damage in patients with IIM. A core set of
      measurements to use in clinical practice was recently proposed. Among laboratory
      features the increase of serum creatine kinase (CK) is considered a hallmark of
      muscle inflammation/damage. However, subjects with persistent CK elevation,
      without any evidence of a definite myopathy, are often seen in clinical practice
      and need a careful assessment. Indeed, CK blood levels can also increase in non
      myopathic conditions, e.g. in case of intense physical exercise, assumption of
      some drugs (statins), muscular dystrophy, muscular trauma or in case of neuro
      muscular disorders which all should be considered in the diagnostic work-up. The
      assessment of patients with IIM and hyperCKemia will be discussed in this paper. 

PMID- 26000161
TI  - Drugs in induction and treatment of idiopathic inflammatory myopathies.
AB  - Idiopathic inflammatory myopathies (IIM) are a rare disease; so far standardized
      therapy has not been adequately defined by national or international guidelines
      or recommendations. Corticosteroids are the mainstay of treatment, but these
      drugs are burdened by several side effects. Thus, additional treatment based on
      immunosuppressive agents, especially azathioprine, methotrexate, mycophenolate
      mofetil and cyclosporine, is often needed. This combinate approach both improves
      the disease response and allows reduction of the dosage of corticosteroids,
      decreasing the risk of steroid-related long-term complications. Biological
      agents, particularly B cell depleting agent, are emergent therapeutic tools for
      refractory cases. Notably, drugs currently used for the therapy of IIM or other
      rheumatologic and non-rheumatologic conditions can induce myopathy. Drug-induced
      myopathies represent a considerable part of the complex topic of muscular
      disorders and should be always considered in the usual diagnostic work-up of a
      subject with muscle disease. Several mechanisms have been advocated to explain
      muscular damage induced by a number of drugs and, although a recovery after drug
      removal is usually observed, severe or persistent myopathy may be observed
      following the administration of some drugs, particularly in subjects with genetic
      predisposition. In this review the traditional and novel therapeutic approaches
      for patients with IIM, particularly biologics, will be discussed and an overview
      on drug-induced myopathies will also be provided. 

PMID- 26000162
TI  - NTRK2 expression levels are reduced in laser captured pyramidal neurons from the
      anterior cingulate cortex in males with autism spectrum disorder.
AB  - BACKGROUND: The anterior cingulate cortex (ACC) is a brain area involved in
      modulating behavior associated with social interaction, disruption of which is a
      core feature of autism spectrum disorder (ASD). Functional brain imaging studies
      demonstrate abnormalities of the ACC in ASD as compared to typically developing
      control patients. However, little is known regarding the cellular basis of these
      functional deficits in ASD. Pyramidal neurons in the ACC are excitatory
      glutamatergic neurons and key cellular mediators of the neural output of the ACC.
      This study was designed to investigate the potential role of ACC pyramidal
      neurons in ASD brain pathology. METHODS: Postmortem ACC tissue from carefully
      matched ASD and typically developing control donors was obtained from two
      national brain collections. Pyramidal neurons and surrounding astrocytes were
      separately collected from layer III of the ACC by laser capture microdissection.
      Isolated RNA was subjected to reverse transcription and endpoint PCR to determine
      gene expression levels for 16 synaptic genes relevant to glutamatergic
      neurotransmission. Cells were also collected from the prefrontal cortex (Brodmann
      area 10) to examine those genes demonstrating differences in expression in the
      ACC comparing typically developing and ASD donors. RESULTS: The level of NTRK2
      expression was robustly and significantly lower in pyramidal neurons from ASD
      donors as compared to typically developing donors. Levels of expression of GRIN1,
      GRM8, SLC1A1, and GRIP1 were modestly lower in pyramidal neurons from ASD donors,
      but statistical significance for these latter genes did not survive correction
      for multiple comparisons. No significant expression differences of any genes were
      found in astrocytes laser captured from the same neocortical area. In addition,
      expression levels of NTRK2 and other synaptic genes were normal in pyramidal
      neurons laser captured from the prefrontal cortex. CONCLUSIONS: These studies
      demonstrate a unique pathology of neocortical pyramidal neurons of the ACC in
      ASD. NTRK2 encodes the tropomyosin receptor kinase B (TrkB), transmission through
      which neurotrophic factors modify differentiation, plasticity, and synaptic
      transmission. Reduced pyramidal neuron NTRK2 expression in the ACC could thereby
      contribute to abnormal neuronal activity and disrupt social behavior mediated by
      this brain region.

PMID- 26000163
TI  - Sugar Silanes: Versatile Reagents for Stereocontrolled Glycosylation via
      Intramolecular Aglycone Delivery.
AB  - A new method for the intramolecular glycosylation of alcohols is described.
      Utilizing carbohydrate-derived silanes, the catalytic dehydrogenative silylation
      of alcohols is followed by intramolecular glycosylation. Appropriate combinations
      of silane position and protecting groups allow highly selective access to beta
      manno, alpha-gluco, or beta-gluco stereochemical relationships as well as 2-azido
      2-deoxy-beta-gluco- and 2-deoxy-beta-glucosides. Intramolecular aglycone delivery
      from the C-2 or C-6 position provides 1,2-cis or 1,2-trans glycosides,
      respectively. Multifunctional acceptor substrates such as hydroxyketones and
      diols are tolerated and are glycosylated in a site-selective manner.

PMID- 26000165
TI  - The 2014 ming k jeang award for excellence in cell & bioscience.
AB  - Three research groups led by Dr. Robert Clarke of Georgetown University Medical
      Center, Washington, DC, USA; Dr. Lixin Wei of Shanghai Jiaotong University,
      Shanghai, China; and Dr. Zhiming Zhang of Xiamen University, Xiamen, Fujian,
      China, won the 2014 Ming K Jeang Award for Excellence in Cell & Bioscience. 

PMID- 26000166
TI  - The developmental relation between aggressive behaviour and prosocial behaviour:
      A 5-year longitudinal study.
AB  - BACKGROUND: Past research has shown links between both children's aggressive
      behaviour and a lack of prosocial behaviour to later maladaptation. Both types of
      behaviours have also been identified as crucial in children's social and
      emotional development and later (mal)adaptation. However, little is known about
      the way they predict each other over time. METHODS: We utilised a large,
      ethnically diverse, longitudinal population sample of girls and boys (N = 1,334)
      to examine the bidirectional cross-lagged links between aggressive and prosocial
      domains of behaviour from age seven to eleven. Teacher, parent and child self
      reports were utilised to assess aggressive behaviour and prosocial behaviour.
      RESULTS: The results revealed that aggressive behaviour measured one year
      predicted decreases in prosocial behaviour in the following year. Conversely,
      prosocial behaviour did not predict changes in aggressive behaviour in the
      subsequent year. Furthermore, peer difficulties were examined and found to be an
      important mediator of the link between aggressive and prosocial behaviour.
      Specifically, peer difficulties mediated the links between aggressive behaviour
      and prosocial behaviour one year later, particularly during the first three years
      of school attendance. CONCLUSIONS: Implications of the findings for the design of
      intervention strategies to reduce children's aggressive behaviour are discussed.

PMID- 26000164
TI  - The endogenous molecular clock orchestrates the temporal separation of substrate
      metabolism in skeletal muscle.
AB  - BACKGROUND: Skeletal muscle is a major contributor to whole-body metabolism as it
      serves as a depot for both glucose and amino acids, and is a highly metabolically
      active tissue. Within skeletal muscle exists an intrinsic molecular clock
      mechanism that regulates the timing of physiological processes. A key function of
      the clock is to regulate the timing of metabolic processes to anticipate time of
      day changes in environmental conditions. The purpose of this study was to
      identify metabolic genes that are expressed in a circadian manner and determine
      if these genes are regulated downstream of the intrinsic molecular clock by
      assaying gene expression in an inducible skeletal muscle-specific Bmal1 knockout
      mouse model (iMS-Bmal1 (-/-) ). METHODS: We used circadian statistics to analyze
      a publicly available, high-resolution time-course skeletal muscle expression
      dataset. Gene ontology analysis was utilized to identify enriched biological
      processes in the skeletal muscle circadian transcriptome. We generated a
      tamoxifen-inducible skeletal muscle-specific Bmal1 knockout mouse model and
      performed a time-course microarray experiment to identify gene expression changes
      downstream of the molecular clock. Wheel activity monitoring was used to assess
      circadian behavioral rhythms in iMS-Bmal1 (-/-) and control iMS-Bmal1 (+/+) mice.
      RESULTS: The skeletal muscle circadian transcriptome was highly enriched for
      metabolic processes. Acrophase analysis of circadian metabolic genes revealed a
      temporal separation of genes involved in substrate utilization and storage over a
      24-h period. A number of circadian metabolic genes were differentially expressed
      in the skeletal muscle of the iMS-Bmal1 (-/-) mice. The iMS-Bmal1 (-/-) mice
      displayed circadian behavioral rhythms indistinguishable from iMS-Bmal1 (+/+)
      mice. We also observed a gene signature indicative of a fast to slow fiber-type
      shift and a more oxidative skeletal muscle in the iMS-Bmal1 (-/-) model.
      CONCLUSIONS: These data provide evidence that the intrinsic molecular clock in
      skeletal muscle temporally regulates genes involved in the utilization and
      storage of substrates independent of circadian activity. Disruption of this
      mechanism caused by phase shifts (that is, social jetlag) or night eating may
      ultimately diminish skeletal muscle's ability to efficiently maintain metabolic
      homeostasis over a 24-h period.

PMID- 26000167
TI  - Optimizing photo-mineralization of aqueous methyl orange by nano-ZnO catalyst
      under simulated natural conditions.
AB  - BACKGROUND: Photo-degradation of organic contaminants into non-hazardous mineral
      compounds is emerging as a strategy to purify water and environment. Tremendous
      research is being done using direct solar light for these purposes. In this paper
      we report on optimum conditions for complete mineralization of aqueous methyl
      orange using lab-prepared ZnO nanopowder catalyst under simulated solar light.
      RESULTS: Nano-scale ZnO powder was prepared in the lab by standard methods, and
      then characterized using electronic absorption spectra, photolumenscence emission
      (PL) spectra, XRD, and SEM. The powder involved a wurtzite structure with ~19 nm
      particles living in agglomerates. Photo-degradation progressed faster under
      neutral or slightly acidic conditions which resemble natural waters. Increasing
      catalyst concentration increased photodegradation rate to a certain limit. Values
      of catalyst turn over number and degradation percentage increased under higher
      light intensity, whereas the quantum yield values decreased. The photocatalytic
      efficiency of nano-ZnO powders in methyl orange photodegradation in water with
      solar light has been affected by changing the working conditions. More
      importantly, the process may be used under natural water conditions with pH
      normally less than 7, with no need to use high concentrations of catalyst or
      contaminant. The results also highlight the negative impact of possible high
      concentrations of CO2 on water purification processes. Effects of other added
      gaseous flows to the reaction mixture are also discussed. CONCLUSION: ZnO nano
      particles are useful catalyst for complete mineralization of organic contaminants
      in water. Photo-degradation of organic contaminants with ZnO nano-particles,
      methyl orange being an example, should be considered for future large scale water
      purification processes under natural conditions.

PMID- 26000168
TI  - Recent developments in computer assisted rehabilitation environments.
AB  - Computer Assisted Rehabilitation Environment (CAREN) is a system that integrates
      a training platform (motion base), a virtual environment, a sensor system (motion
      capture) and D-flow software. It is useful for both diagnostic and therapeutic
      use. The human gait pattern can be impaired due to disease, trauma or natural
      decline. Gait analysis is a useful tool to identify impaired gait patterns.
      Traditional gait analysis is a very time consuming process and therefore only
      used in exceptional cases. With new systems a quick and extensive analysis is
      possible and provides useful tools for therapeutic purposes. The range of systems
      will be described in this paper, highlighting both their diagnostic use and the
      therapeutic possibilities. Because wounded warriors often have an impaired gait
      due to amputations or other extremity trauma, these systems are very useful for
      military rehabilitative efforts. Additionally, the virtual reality environment
      creates a very challenging situation for the patient, enhancing their
      rehabilitation experience. For that reason several Armed Forces have these
      systems already in use. The most recent experiences will be discussed; including
      new developments both in the extension of the range of systems and the
      improvement and adaptation of the software. A new and promising development, the
      use of CAREN in a special application for patients with post-traumatic stress
      disorder (PTSD), will also be reviewed. 

PMID- 26000169
TI  - Keeping the right time in space: importance of circadian clock and sleep for
      physiology and performance of astronauts.
AB  - The circadian clock and sleep are essential for human physiology and behavior;
      deregulation of circadian rhythms impairs health and performance. Circadian
      clocks and sleep evolved to adapt to Earth's environment, which is characterized
      by a 24-hour light-dark cycle. Changes in gravity load, lighting and work
      schedules during spaceflight missions can impact circadian clocks and disrupt
      sleep, in turn jeopardizing the mood, cognition and performance of orbiting
      astronauts. In this review, we summarize our understanding of both the influence
      of the space environment on the circadian timing system and sleep and the impact
      of these changes on astronaut physiology and performance. 

PMID- 26000170
TI  - Effects and mechanisms of a microcurrent dressing on skin wound healing: a
      review.
AB  - The variety of wound types has resulted in a wide range of wound dressings, with
      new products frequently being introduced to target different aspects of the wound
      healing process. The ideal wound dressing should achieve rapid healing at a
      reasonable cost, with minimal inconvenience to the patient. Microcurrent
      dressing, a novel wound dressing with inherent electric activity, can generate
      low-level microcurrents at the device-wound contact surface in the presence of
      moisture and can provide an advanced wound healing solution for managing wounds.
      This article offers a review of the effects and mechanisms of the microcurrent
      dressing on the healing of skin wounds. 

PMID- 26000171
TI  - Effects of microwave radiation on brain energy metabolism and related mechanisms.
AB  - With the rapid development of electronic technologies, anxiety regarding the
      potential health hazards induced by microwave radiation (MW) has been growing in
      recent years. The brain is one of the most sensitive target organs for microwave
      radiation, where mitochondrial injury occurs earlier and more severely than in
      other organs. Energy metabolism disorders do play an important role during the
      process of microwave radiation-induced brain damage. In this paper, we will
      review the biological effects of microwave radiation, the features of brain
      energy supply and consumption and the effects of microwave radiation on
      mitochondrial energy metabolism and potential related mechanisms. 

PMID- 26000172
TI  - HBsAg seroprevalence among Senegalese militaries.
AB  - BACKGROUND: Chronic hepatitis is a major public health problem. Hepatitis B virus
      is the primary cause, and Hepatitis B and C together are responsible for 60% of
      cirrhosis and 80% of hepatocellular carcinomas. This study measured the
      prevalence of HBsAg among Senegalese military to develop an appropriate strategy
      to prevent cirrhosis and hepatocellular carcinoma. METHODS: We conducted a
      descriptive cross-sectional study among Senegalese military aged 25 to 60 years.
      A sample of 1224 participants was selected following a two-level-stratification.
      The mark of surface HBs antigen using chemiluminescence concerned 1195
      participants. The presence of HBsAg was analyzed according to age, marital
      status, alcohol consumption and glomerular filtration rate. Epi-info6fr and R
      software were used, respectively, for data capture and analyses. A Chi-square
      test was performed to compare proportions considering a significance level of 5%
      and a confidence interval of 95%. RESULTS: The average age was 39.8 +/- 9.2
      years. Participants in the age groups of 25-34 years, 45-60 years and 35-44 years
      were respectively 30.7%, 34.4% and 34.9% of the sample. Married persons
      represented 82.6% of participants and 17.08% were single. Most participants were
      educated (99%), and 56% had reached at least secondary school level. Alcohol
      consumption was at 11.5%. The HBsAg prevalence rate was 10.8% [9.1% to 12.7%]
      with a significant difference between age groups (P < 0.001), which ranged from
      5.6% for 45-60 years, 9.62% for 25-34 years to 16.9% for 35-44 years. Marital
      status and alcohol consumption did not affect the carriage of HBsAg. HBsAg
      prevalence was more common among participants who had a glomerular filtration
      rate greater than 90 ml/min. Transaminases rate exceeded the normal threshold for
      43 participants (3.6%); the increase was 6.6% [2.7% to 11.8%] for HBsAg carriers
      and 3.2% [1.2% to 6.7%] for alcohol users. CONCLUSIONS: The high prevalence of
      HBsAg in the military requires the implementation of an effective prevention and
      care program to reduce the risk of cirrhosis and hepatocellular carcinoma and
      contribute to reducing the burden of communicable diseases, such as hepatitis and
      HIV/AIDS, and non-communicable diseases.

PMID- 26000173
TI  - Ebola virus disease: from epidemiology to prophylaxis.
AB  - The outbreak of Ebola virus disease (EVD) continues to spread through West
      Africa. Since the first report of EVD in March 2014, the number of cases has
      increased rapidly, with the fatality rate of >50%. The most prevalent Ebola virus
      belongs to the species of Zaire ebolavirus, with a fatality rate as high as 90%.
      Although there were cases introduced into other continents, Africa is the endemic
      area where fruit bats and apes are suspected to be Ebola virus carriers. The
      virus might be transmitted from the host animals to humans if humans consume raw
      or not fully cooked and contaminated meats. However, human-to-human transmission
      via close contact is the major route of current outbreaks. EVD can occur during
      any season and affect people of any race and age group. Direct contact with body
      fluids of EVD patients or living in contaminated environments greatly increases
      the risk of being infected. Transmission via aerosol less likely, but
      transmission via virus-containing droplets is possible in humans. Thus, health
      care providers are facing danger of getting Ebola virus infection. To date,
      vaccines, drugs and/or therapies to prevent Ebola virus infection or treat EVD
      are limited. Medical workers should follow the current standard prophylactic
      procedures. The military can orchestrate efficient care to mass EVD patients.
      Although it is necessary to speed up the pace of developing effective vaccine and
      therapeutics for the prevention and treatment of EVD, public health prevention
      and management should be important issue at present to control the spread of this
      disease cost-effectively. 

PMID- 26000174
TI  - Failure to fire after an electrical injury - a complex syndrome in a soldier.
AB  - Complex regional pain syndrome (CRPS) is a disorder characterized by an
      intractable, disabling pain of the affected limb. It is triggered by various
      injuries and is often resistant to standard therapy. We report a young soldier
      with CRPS of the right hand sustained from an electrical injury, who had
      improvement in resting pain with Zoledronic acid. In this report, we discuss the
      therapeutic options and the role of bisphosphonates in CRPS. 

PMID- 26000175
TI  - Predictors of HIV/AIDS Related Ocular Manifestations among HIV/AIDS Patients in
      Felege Hiwot Referral Hospital, Northwest Ethiopia.
AB  - Background. Ocular manifestations in people living with HIV/AIDS are varied and
      affect almost all the structures of eye leading to visual impairment or
      blindness. Therefore, the aim of this study was to identify the predictors of HIV
      related ocular manifestation among ART clinic clients. Methods. Institution based
      cross-sectional study was employed among ART clients at Felege Hiwot referral
      hospital, northwest Ethiopia. The study was conducted from 1 January 2013 to 30
      January 2013. A total of 369 systematically and randomly selected clients were
      included in the study. Data were collected using structured questionnaires and
      ophthalmologic clinical examination. Data were entered and analyzed using SPSS
      version 16.0. Binary and multivariable logistic regression analyses were computed
      to identify independent predictors of HIV related ocular manifestation. Results.
      Twenty-five percent (25.7%) of HIV patients had ocular manifestations. The three
      most frequent signs were Squamoid Conjuctival growth (26.9%), ophthalmic herpes
      zoster (22.1%), and Bacterial Conjuctivitis (17.2%). History of eye problem, CD4
      count, and visual acuity of the eye were the predictors of HIV related ocular
      manifestation. Conclusion. In this study, a higher proportion of ocular
      manifestations were detected in HIV/AIDS patients. Visual acuity and CD4 counts
      were the independent predictors of ocular manifestations. This finding gives an
      insight for policy makers and concerned body to integrate ophthalmic examination
      in ART clinics to improve the health condition of HIV/ADIS patients. 

PMID- 26000176
TI  - Effect of four approaches to oral feeding progression on clinical outcomes in
      preterm infants.
AB  - Background. The purpose of this study of preterm infants was to test the effect
      of four approaches to the time of transition from gavage to full oral feedings,
      time to discharge, and weight gain during the transition. Methods. A randomized
      experimental design was used with four intervention groups: early start (32
      weeks' postmenstrual age)/slow progressing experience (gradually increasing oral
      feedings offered per day); early start/maximum experience (oral feedings offered
      at every feeding opportunity); late start (34 weeks' postmenstrual age)/slow
      progressing experience; and late start/maximum experience. Results. The analysis
      included 86 preterm infants. Once oral feedings were initiated, infants in the
      late start/maximum experience group achieved full oral feeding and were
      discharged to home significantly sooner than infants in either early start group.
      Although not significantly different, these infants also achieved these outcomes
      sooner than infants in the late start/slow progressing experience group. There
      were no differences in weight gain across groups. Conclusions. Results suggest
      starting oral feedings later in preterm infants may result in more rapid
      transition to full oral feedings and discharge although not at early postnatal
      ages. Provision of a more consistent approach to oral feeding may support infant
      neurodevelopment and reduce length of hospitalization. 

PMID- 26000177
TI  - Traumatic displacement of maxillary permanent canine into the vestibule of the
      mouth.
AB  - Dentoalveolar injuries are common and are caused by many factors. Dental trauma
      requires special consideration when a missing tooth or tooth fracture accompanies
      soft tissue laceration. A tooth or its fragment occasionally penetrates into soft
      tissue and may cause severe complications. This report presents a case of delayed
      diagnosis and management of a displaced tooth in the vestibule of the mouth
      following dentoalveolar injury. This report suggests that radiography can lead to
      an early diagnosis and surgical removal of an embedded tooth in the soft tissue. 

PMID- 26000178
TI  - Decontamination using a desiccant with air powder abrasion followed by biphasic
      calcium sulfate grafting: a new treatment for peri-implantitis.
AB  - Peri-implantitis is characterized by inflammation and crestal bone loss in the
      tissues surrounding implants. Contamination by deleterious bacteria in the peri
      implant microenvironment is believed to be a major factor in the etiology of peri
      implantitis. Prior to any therapeutic regenerative treatment, adequate
      decontamination of the peri-implant microenvironment must occur. Herein we
      present a novel approach to the treatment of peri-implantitis that incorporates
      the use of a topical desiccant (HYBENX), along with air powder abrasives as a
      means of decontamination, followed by the application of biphasic calcium sulfate
      combined with inorganic bovine bone material to augment the intrabony defect. We
      highlight the case of a 62-year-old man presenting peri-implantitis at two
      neighboring implants in positions 12 and 13, who underwent access flap surgery,
      followed by our procedure. After an uneventful 2-year healing period, both
      implants showed an absence of bleeding on probing, near complete regeneration of
      the missing bone, probing pocket depth reduction, and clinical attachment gain.
      While we observed a slight mucosal recession, there was no reduction in
      keratinized tissue. Based on the results described within, we conclude that the
      use of HYBENX and air powder abrasives, followed by bone defect grafting,
      represents a viable option in the treatment of peri-implantitis. 

PMID- 26000179
TI  - Pitfalls in suspected acute aortic syndrome: impact of appropriate and if
      required repeated imaging.
AB  - The incidence of acute aortic syndrome is low, but the spontaneous course is
      often life-threatening. Adequate ECG-gated imaging is fundamental within the
      diagnostic workup. We here report a case of a 53-year-old man presenting with
      atypical chest pain, slight increase of D dimers at admission, and extended
      diameter of the ascending aorta accompanied by mild aortic regurgitation.
      Interpretation of an initial contrast-enhanced computed tomography was false
      negative due to inadequate gating and motion artifacts, thereby judging a tiny
      contrast signal in the left anterior quadrant of the ascending aorta as a
      pseudointimal flap. By hazard, cardiac magnetic resonance imaging demonstrated an
      ulcer-like lesion superior to the aortic root, leading to aortic surgery at the
      last moment. As sensitivity of imaging is not 100%, this example underlines that
      second imaging studies might be necessary if the first imaging is negative, but
      the clinical suspicion still remains high. 

PMID- 26000180
TI  - A pelvic pseudotumor in a nonhemophilic patient: an unusual presentation.
AB  - Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2
      percent of individuals with severe factor VIII or factor IX deficiency. A 35-year
      old male presented with a swelling in the right lower abdomen for 3 months. There
      was no history of trauma. Examination revealed a swelling over the right iliac
      fossa. Right hip showed 30 degrees  flexion deformity. Blood investigations like
      complete blood count, APTT, PT, bleeding and clotting time, and fibrinogen were
      all normal. Plain radiograph and MRI showed a lytic lesion in the right iliac
      wing. Excision biopsy of the swelling showed organized hematoma with a fibrous
      capsule suggestive of a pseudotumor. Further haematological workup like factors
      VIII and IX was normal. At 2 years follow-up, there was no recurrence. We report
      this case of pseudotumour in patient without any bleeding disorder. Such case has
      not been reported in literature to the best of our knowledge. 

PMID- 26000181
TI  - Anaerobic Spondylodiscitis due to Fusobacterium Species: A Case Report Review of
      the Literature.
AB  - Spondylodiscitis caused by Fusobacterium species is rare. Most cases of
      spontaneous spondylodiscitis are caused by Staphylococcus aureus and most
      postoperative cases are caused by Staphylococcus aureus or coagulase-negative
      staphylococci. Escherichia coli is the most common Gram-negative organism causing
      spondylodiscitis. Fusobacterium species are unusual causes for anaerobic
      spondylodiscitis. We report the case of a patient with spontaneous L2-L3
      spondylodiscitis, vertebral osteomyelitis, and epidural abscess caused by
      Fusobacterium species and review the literature for patients with Fusobacterium
      spondylodiscitis. 

PMID- 26000182
TI  - A case of newly diagnosed klippel trenaunay weber syndrome presenting with
      nephrotic syndrome.
AB  - Klippel Trenaunay Weber syndrome (KTWS) is a rare disease characterized by
      hemihypertrophy, variceal enlargement of the veins, and arteriovenous (AV)
      malformations. Renal involvement in KTWS is not known except in rare case
      reports. Herein, we present a case of KTWS with nephrotic syndrome. A 52-year-old
      male was admitted due to dyspnea and swelling of the body for the last three
      months. The pathological physical findings were diffuse edema, decreased lung
      sounds at the right basal site, increased diameter and decreased length of the
      left leg compared with the right one, diffuse variceal enlargements, and a few
      hemangiomatous lesions on the left leg. The pathological laboratory findings were
      hypoalbuminemia, hyperlipidemia, increased creatinine level (1.23 mg/dL), and
      proteinuria (7.6 g/day). Radiographic pathological findings were cystic lesions
      in the liver, spleen, and kidneys, splenomegaly, AV malformation on the left
      posterolateral thigh, and hypertrophy of the soft tissues of the proximal left
      leg. He was diagnosed to have KTWS with these findings. Renal biopsy was
      performed to determine the cause of nephrotic syndrome. The pathologic
      examination was consistent with focal segmental sclerosis (FSGS). He was started
      on oral methylprednisolone at the dosage of 1 mg/kg and began to be followedup in
      the nephrology outpatient clinic. 

PMID- 26000183
TI  - Ruptured Arteriovenous Malformation Presenting with Kernohan's Notch.
AB  - AVMs are congenital lesions that predispose patients to intracranial hemorrhage
      and resultant neurological deficits. These deficits are often focal and due to
      the presence of local neurologic disruption from hemorrhage in the contralateral
      cerebral hemisphere. We present a rare case of a patient with ipsilateral
      neurological deficits due to Kernohan's Notch phenomenon resulting from
      hemorrhage from an AVM. A 31-year-old woman with seizures underwent MR and
      angiographic imaging which confirmed an unruptured left parietal AVM. The patient
      declined treatment and presented with obtundation 4 years later. Imaging revealed
      an acute left parietal ICH and SDH with significant mass effect. The patient
      underwent emergent hemicraniectomy and hematoma evacuation. Postoperatively, she
      made significant improvement and was following commands contralaterally with
      ipsilateral hemiplegia. MR imaging revealed right Kernohan's Notch. The patient
      had significant rehabilitation with neurological improvement. She eventually
      underwent elective embolization followed by subsequent surgical resection and
      bone replacement. Three years from the initial hemorrhage, the patient had only
      mild left-sided weakness and ambulates without assistance. A false localizing
      sign, Kernohan's Notch phenomenon, should be considered in the setting of AVM
      hemorrhage with paradoxical motor impairment and can be identified through MRI. 

PMID- 26000184
TI  - Vulvar metastasis from bladder cancer.
AB  - Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity;
      few cases are reported in the English literature. In this paper, we describe the
      clinical and pathological characteristics, evolution, and treatment of a patient
      with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief
      review of the reported cases in the literature. 

PMID- 26000185
TI  - Uterine Necrosis Associated with Fusobacterium necrophorum Infection.
AB  - Fusobacterium necrophorum is infrequently implicated as a pathogenic organism.
      When pathogenic, the typical clinical presentation is that of pharyngitis,
      cervical adenopathy, and unilateral thrombophlebitis of the internal jugular
      vein. Infections caused by Fusobacterium necrophorum within the fields of
      obstetrics and gynecology have been infrequently reported. We describe a 19-year
      old woman who underwent a cesarean delivery complicated by sepsis and purulent
      uterine necrosis secondary to Fusobacterium necrophorum infection. 

PMID- 26000186
TI  - Glanzmann's Thrombasthenia Diagnosed following Knee Arthroscopy.
AB  - A 41-year-old man with an unremarkable medical history presented with a painful
      knee after a sports injury. He was diagnosed with a medial meniscal tear.
      Symptoms did not abate after 6 months of physical therapy, and he underwent
      arthroscopic partial medial meniscectomy. A week after beginning physical therapy
      he experienced a knee effusion, decreased ROM, and inability to flex his
      quadriceps. His knee was aspirated. Blood tests were ordered and his complete
      blood count, liver functions tests, and INR/PTT were normal. The patient had
      recurrent effusions requiring three additional joint aspirations. Ten weeks after
      the initial surgery, the patient underwent a second arthroscopy, during which a
      hematoma was removed and a synovectomy performed. The patient continued bleeding
      from the incisions after portals were sutured, and he was admitted to the
      hospital. A hematologist was consulted and comprehensive platelet aggregation
      testing revealed previously undiagnosed Glanzmann's thrombasthenia. The patient
      began treatment with platelet infusions and desmopressin and progressed to a full
      recovery. Clinical suspicion for surgical patients with unusual repetitive
      postoperative bleeding should include previously undetected rare bleeding
      disorders even in adults. 

PMID- 26000187
TI  - Secondary subacromial impingement after valgus closing-wedge osteotomy for
      proximal humerus varus.
AB  - A 31-year-old construction worker had been suffering from both the motion pain
      and the restriction of elevation in his right shoulder due to severe varus
      deformity of humeral neck, which occurred after proximal humeral fracture. The
      angle for shoulder flexion and abduction was restricted to 50 and 80 degrees,
      respectively. Valgus closing-wedge osteotomy followed by the internal fixation
      using a locking plate was carried out at 12 months after injury. Postoperatively,
      the head-shaft angle of the humerus improved from 65 to 138 degrees. Active
      flexion and abduction angles improved from 80 to 135 degrees and from 50 to 135
      degrees, respectively. However, the patient complained from a sharp pain with a
      clicking sound during shoulder abduction even after removal of the locking plate.
      Since subacromial steroid injection temporarily relieved his shoulder pain, we
      assumed that the secondary subacromial impingement was provoked after osteotomy.
      Thus, arthroscopic subacromial decompression was carried out at 27 months after
      the initial operation, which finally relieved his symptoms. In the valgus closing
      wedge osteotomy, surgeons should pay attention to the condition of subacromial
      space to avoid causing the secondary subacromial impingement. 

PMID- 26000188
TI  - Lipoleiomyoma of the uterus and primary ovarian leiomyoma in a postmenopausal
      woman: two rare entities in the same individual.
AB  - Uterine lipoleiomyomas are rare benign tumours that are composed of various
      mixtures of smooth muscle and mature fat tissue. Leiomyomas, which arise
      primarily in the ovary, are extremely rare tumours that account for 0.5-1% of all
      benign ovarian tumours. To the best of our knowledge, we present the first case
      of an ovarian leiomyoma coexisting with a uterine lipoleiomyoma in the
      postmenopausal period. A 59-year-old, gravida 4, para 3, postmenopausal woman
      exhibited pelvic discomfort and increased frequency of micturition. A pelvic
      examination revealed a solid, tender mass on the left side that could not be
      clearly separated from the uterus. She underwent a laparotomy with an initial
      diagnosis of a left ovarian mass. She had previously undergone a total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. A histopathological examination
      revealed a uterine lipoleiomyoma, composed of variable amounts of smooth muscle
      cells and mature adipocytes and a right ovarian leiomyoma composed of interlacing
      bundles and fascicles of spindle cells. The coexistence of these two rare
      entities in the same individual may represent a common pathway as a stimulating
      agent. This case may help to clarify the pathogenesis of these lesions. 

PMID- 26000189
TI  - NIV-Helmet in Severe Hypoxemic Acute Respiratory Failure.
AB  - Noninvasive ventilation (NIV) is a method to be applied in acute respiratory
      failure, given the possibility of avoiding tracheal intubation and conventional
      ventilation. A previous healthy 5-month-old boy developed low-grade intermittent
      fever, flu-like symptoms, and dry cough for 3 days. On admission, he showed
      severe respiratory distress with SpO2/FiO2 ratio of 94. Subsequent evaluation
      identified an RSV infection complicated with an increase of inflammatory
      parameters (reactive C protein 15 mg/dL). Within the first hour after NIV-helmet
      CPAP SpO2/FiO2 ratio increased to 157. This sustained improvement allowed the
      continuing of this strategy. After 102 h, he was disconnected from the helmet
      CPAP device. The NIV use in severe hypoxemic acute respiratory failure should be
      carefully monitored as the absence of clinical improvement has a predictive value
      in the need to resume to intubation and mechanical ventilation. We emphasize that
      SpO2/FiO2 ratio is a valuable monitoring instrument. Helmet interface use
      represents a more comfortable alternative for providing ventilatory support,
      particularly to small infants, which constitute a sensitive group within
      pediatric patients. 

PMID- 26000190
TI  - Two mutations in surfactant protein C gene associated with neonatal respiratory
      distress.
AB  - Multiple mutations of surfactant genes causing surfactant dysfunction have been
      described. Surfactant protein C (SP-C) deficiency is associated with variable
      clinical manifestations ranging from neonatal respiratory distress syndrome to
      lethal lung disease. We present an extremely low birth weight male infant with an
      unusual course of respiratory distress syndrome associated with two mutations in
      the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26
      days and was treated with 5 subsequent doses of surfactant with temporary and
      short-term efficacy. He was discharged at 37 weeks of postconceptional age
      without any respiratory support. During the first 16 months of life he developed
      five respiratory infections that did not require hospitalization. Conclusion.
      This mild course in our patient with two mutations is peculiar because the
      outcome in patients with a single SFTPC mutation is usually poor. 

PMID- 26000191
TI  - Three patients needing high doses of valproic Acid to get therapeutic
      concentrations.
AB  - Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses
      >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases,
      have never been published. Case 1 received VPA for seizures and schizophrenia and
      had >50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA
      concentrate was prescribed for years but this dose led to an intoxication when
      switched to the enterocoated divalproex sodium formulation, requiring a normal
      dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t = -9.6;
      df = 6.3, p < 0.001) during the VPA concentrate therapy, possibly due to
      autoinduction in that formulation. Case 2 had VPA for schizoaffective psychosis
      with 10 VPA concentrations during an 8-week admission. To maintain a VPA level
      >=50 MUg/mL, VPA doses increased from 1500 to 4000 mg/day. Case 3 had tuberous
      sclerosis and epilepsy and was followed up for >4 years with 137 VPA
      concentrations. To maintain VPA concentrations >=50 MUg/mL, VPA doses increased
      from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the
      VPA dose were strongly correlated (r around 0.90; p < 0.001) with almost no
      change after controlling for VPA concentrations, indicating progressive
      autoinduction that increased with time. 

PMID- 26000192
TI  - Unusual presentation of testicular cancer with tumor thrombus extending to the
      inferior vena cava.
AB  - A 45-year-old man with a left testis tumor with a 25 mm para-aortic lymph node
      swelling, multiple bilateral pulmonary metastases, bilateral pulmonary embolism,
      and inferior vena cava (IVC) thrombus underwent a radical orchidectomy in our
      institution. The thrombus extended from the left gonadal vein to the left renal
      vein to the IVC. The fluorine-18 fluorodeoxyglucose (f-FDG) positron emission
      tomography (PET) computerized tomography (CT) demonstrated a hypermetabolic focus
      in the retroperitoneum and in the IVC thrombus. Before orchidectomy only lactate
      dehydrogenase (LDH) was high but all the serum tumor markers increased
      postoperatively. The tumor was staged pT1N2M1aS1, which was an intermediate
      prognosis, based on the International Germ Cell Cancer Collaborative Group
      consensus (IGCCCG). After 4 courses of bleomycin, etoposide, and cisplatin (BEP)
      chemotherapy the patient's tumor markers normalized and the thrombus disappeared.
      There was only one residual retroperitoneal lymph node M1. Retroperitoneal lymph
      node dissection was performed. The pathological examination revealed only
      necrotic tissues. The patient has been disease-free since surgery. 

PMID- 26000193
TI  - A vision for the innovative study of fungal biology in China: Presidential
      address.
AB  - I am proud to be elected as the sixth president of the Mycological Society of
      China, and highly pleased to have a chance to share my personal opinion here with
      my fellow mycologists and students regarding the innovative performance of fungal
      biology studies in China. A stepwise buildup of knowledge and sharp scientific
      vision is the prerequisite for innovative studies. Taken together with the most
      advanced techniques and elegant experimental designs, the scholars would have a
      better chance to acquire novel and conceptual results rather than the "me too"
      stories by focusing on the mechanisms related with fungal unique biology.

PMID- 26000194
TI  - Are heterotrophic and silica-rich eukaryotic microbes an important part of the
      lichen symbiosis?
AB  - We speculate that heterotrophic and/or silica-rich eukaryotic microorganisms
      maybe an important part of the lichen symbiosis. None of the very few studies of
      heterotrophic protists associated with lichens have considered the possibility
      that they may be of functional significance in the lichen symbiosis. Here we
      start to develop, currently speculative, theoretical ideas about their potential
      significance. For example, all the protist taxa identified in lichens we sampled
      in Ohio USA depend on silica for growth and construction of their cell walls,
      this could suggest that silica-rich lichen symbionts may be significant in the
      biogeochemistry of the lichen symbiosis. We also present arguments suggesting a
      role for protists in nitrogen cycling within lichen thalli and a potential role
      in controlling bacterial populations associated with lichens. In this necessarily
      speculative paper we highlight areas for future research and how newer
      technologies may be useful for understanding the full suite of organisms involved
      in the lichen symbiosis.

PMID- 26000196
TI  - Pleurotus biomass production on vinasse and its potential use for aquaculture
      feed.
AB  - The vinasse is a by-product generated during the manufacture of alcohol from
      sugarcane fermentation. Rich in organic matter, it is known that the vinasse has
      the potential to be used as a source of nutrients for plants as well as
      microorganisms. In this study, the fungi Pleurotus sajor-caju, P. ostreatus, P.
      albidus and P. flabellatus were cultivated in vinasse and utilised as a
      complementary diet for Danio rerio fish. The fungi mycelia cultured in vinasse
      for 15 days were lyophilised and offered to the fishes at a rate of 2%
      (medium/body weight) for 28 days. P. albidus produced the highest biomass (16.27
      g L-1). Bromatological analysis of mycelia showed similar values to commercial
      rations. Toxicity tests showed that fish survival was 100% and no significant
      biomass loss was observed, indicating that the tested fungi grown in vinasse
      showed no toxicity. Our results showed that vinasse is a promising by-product for
      fungal growth and the mycelia of Pleurotus sp. fungi can be included in the diets
      of fish as a nutritional supplement.

PMID- 26000197
TI  - Suillus indicus sp. nov. (Boletales, Basidiomycota), a new boletoid fungus from
      northwestern Himalayas, India.
AB  - The new species Suillus indicus is described based on the morpho-anatomical
      description and molecular analysis of basidiomes found in conifer forests of the
      northwestern Himalayas, India. Morphologically, the key diagnostic
      characteristics of the new taxon are brownish-orange to reddish-brown pileus with
      low obtuse umbo, brownish-red to reddish-brown fibrillose squamules over the
      pileal surface, and absence of fibrillose squamules and glandular dots on the
      stipe surface. Sequences derived from the internal transcribed spacer region of
      basidiomes and culture demonstrated that the species is clearly distinct from
      other known taxa of Suillus and new to science.

PMID- 26000195
TI  - Phylogenetic and chemical diversity of fungal endophytes isolated from Silybum
      marianum (L) Gaertn. (milk thistle).
AB  - Use of the herb milk thistle (Silybum marianum) is widespread, and its chemistry
      has been studied for over 50 years. However, milk thistle endophytes have not
      been studied previously for their fungal and chemical diversity. We examined the
      fungal endophytes inhabiting this medicinal herb to determine: (1) species
      composition and phylogenetic diversity of fungal endophytes; (2) chemical
      diversity of secondary metabolites produced by these organisms; and (3)
      cytotoxicity of the pure compounds against the human prostate carcinoma (PC-3)
      cell line. Forty-one fungal isolates were identified from milk thistle comprising
      25 operational taxonomic units based on BLAST search via GenBank using published
      authentic sequences from nuclear ribosomal internal transcribed spacer sequence
      data. Maximum likelihood analyses of partial 28S rRNA gene showed that these
      endophytes had phylogenetic affinities to four major classes of Ascomycota, the
      Dothideomycetes, Sordariomycetes, Eurotiomycetes, and Leotiomycetes. Chemical
      studies of solid-substrate fermentation cultures led to the isolation of four new
      natural products. In addition, 58 known secondary metabolites, representing
      diverse biosynthetic classes, were isolated and characterized using a suite of
      nuclear magnetic resonance and mass spectrometry techniques. Selected pure
      compounds were tested against the PC-3 cell line, where six compounds displayed
      cytotoxicity.

PMID- 26000198
TI  - Endomycorrhizal association of Funneliformis mosseae with transformed roots of
      Linum usitatissimum: germination, colonization, and sporulation studies.
AB  - Spores of arbuscular mycorrhizal (AM) fungus Funneliformis mosseae (Nicolson &
      Gerdemann) Walker & Schuessler were cultured in association with transformed
      roots of Linum usitatissimum L. (Linaceae) for the first time on modified Strullu
      Romand medium (pH 5.5) in monoxenic culture. Germ tubes emerged through the spore
      wall in 88% of spores after 5 days. Hyphal contact with transformed linum roots
      was observed 5 days after co-cultivation. Paris-type arbuscules and hyphal coils
      were seen. Extra-radical branched absorbing structures were common. Terminal and
      intercalary secondary spores were also formed. Spore viability when assessed
      using vital dye staining (MTT test) was 83%. Secondary spores that proved viable
      were subsequently transferred from in vitro to in vivo culture where Arum-type
      arbuscules, intra-radical intercellular hyphae, and extra-radical spores were
      observed. The procedure established shows potential in AM inoculum mass
      production and possibility in application.

PMID- 26000199
TI  - Synopsis of Phyllosticta in China.
AB  - The generic concept of Phyllosticta has undergone substantial changes since its
      establishment in 1818. The existence of conidia with a mucilaginous sheath and an
      apical appendage is synapomorphic for Phyllosticta species, which has been shown
      in recent molecular phylogenetic studies. Thus a natural classification of
      Phyllosticta species should emphasize above morphological characters. Many names
      in Phyllosticta, both published in the scientific literatures and in publically
      accessible databases, need updating. In China, more than 200 species names in
      Phyllosticta have been recorded, of which, 158 species names are reviewed here
      based on their morphological descriptions and molecular data. Only 20 species of
      Phyllosticta are accepted from China. Other records of Phyllosticta refer to
      Phoma (89 records), Asteromella (14 records), Boeremia (9 records), Phomopsis (7
      records) and Microsphaeropsis (1 record), with 19 names of uncertain generic
      classification. This work demonstrates an urgent need for the re-assessment of
      records of Phyllosticta worldwide.

PMID- 26000200
TI  - Adherence with general healthcare among internal medicine outpatients with mental
      health treatment histories.

PMID- 26000201
TI  - Diagnostic Stability of Internet Addiction in Obsessive-compulsive Disorder: Data
      from a Naturalistic One-year Treatment Study.
AB  - Whether internet addiction should be categorized as a primary psychiatric
      disorder or the result of an underlying psychiatric disorder still remains
      unclear. In addition, the relationship between internet addiction and obsessive
      compulsive disorder remains to be explored. We hypothesized that internet
      addiction is a manifestation of underlying psychopathology, the treatment of
      which will improve internet addiction. We enrolled 34 control subjects (with or
      without internet addiction) and compared them to 38 patients with "pure"
      obsessive-compulsive disorder (with or without internet addiction). Internet
      addiction and obsessive-compulsive disorder were diagnosed based on Young's
      Diagnostic Questionnaire and Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV), respectively. Age and Internet Addiction Test
      scores were comparable in both the control (years: 26.87+/-6.57; scores: 43.65+/
      11.56) and obsessive-compulsive disorder groups (years: 27.00+/-6.13 years,
      p=0.69; scores: 43.47+/-15.21, p=0.76). Eleven patients with obsessive-compulsive
      disorder (28.95%) were diagnosed with internet addiction as compared to three
      control subjects (p=0.039). In the obsessive-compulsive disorder group, no
      difference in the Yale-Brown Obsessive Compulsive Scale (24.07+/-3.73 non
      internet addiction, 23.64+/-4.65 internet addiction; p=0.76) score was seen
      between the internet addiction/obsessive-compulsive disorder and non-internet
      addiction/obsessive-compulsive disorder groups. As expected, the Internet
      Addiction Test scores were higher in the internet addiction/obsessive-compulsive
      disorder group (64.09+/-9.63) than in the non-internet addiction/obsessive
      compulsive disorder group (35.07+/-6.37; p=0.00). All enrolled patients with
      obsessive-compulsive disorder were subsequently treated for a period of one year.
      Treatment of obsessive-compulsive disorder improved Yale-Brown Obsessive
      Compulsive Scale and Internet Addiction Test scores over time. At 12 months, only
      two of the 11 patients with obsessive-compulsive disorder (18.18%) fulfilled the
      Young's Diagnostic Questionnaire criteria for internet addiction. In conclusion,
      treatment of the underlying disorder improved internet addiction. 

PMID- 26000202
TI  - Atypical myopathy: pentazocine induced.
AB  - Pentazocine is a mixed agonist/antagonist opioid analgesic agent that can induce
      an atypical myopathy following intramuscular injections. This iatrogenic myopathy
      is rare, typified by fibrosis, and should be differentiated from other
      myopathies. We describe a case of pentazocine-induced myopathy that caused
      wasting of musculature in the gluteal region bilaterally and stiffness and woody
      induration in the legs of 42-year-old man. Though rare, clinicians should be
      alerted to this potential side effect and avoid repeated administration of
      intramuscular pentazocine. 

PMID- 26000203
TI  - Patient-Centered Outcomes Research (PCOR): How Can We Optimize Outcomes in CNS
      Research?
AB  - BACKGROUND: Patient-centered outcomes research increases patient involvement in
      health-related decisions with better information of benefits, risks, and options
      as it pertains to patient health. Patient-centered outcomes research is valuable
      for improving patient options in general; however, the vulnerability of patients
      with certain central nervous system conditions and their variable capacity to
      consent may pose significant challenges. Methods/review: Authors acknowledge the
      historical issues and address needs regarding better dissemination of knowledge
      in central nervous system conditions like dementia, depression, and
      schizophrenia. Authors propose ethical safeguards necessary to carry out sound
      patient-centered outcomes research in this unique population.
      Discussion/recommendations: To facilitate ethical patient-centered outcomes
      research, researchers must 1) assess the individual's mental capacity to provide
      consent, 2) determine vulnerability and risk of conducting research in specific
      subgroups, and 3) consider appointment of legally authorized representatives
      and/or consent monitors to ensure accurate understanding of research and ongoing
      direct communication with patients, especially when their future prognosis is
      unpredictable.

PMID- 26000204
TI  - Immunosuppressive mechanisms of human bone marrow derived mesenchymal stromal
      cells in BALB/c host graft versus host disease murine models.
AB  - BACKGROUND: Mesenchymal stromal cells (MSCs) are proven to have immunosuppressive
      functions via various mechanisms. These mechanisms were demonstrated by
      administering bone marrow derived human MSCs (hMSCs) to graft versus host disease
      (GVHD) murine models. METHODS: BALB/c host mice were irradiated prior to
      receiving C57BL/6 donor T cell depleted bone marrow (TCDBM) cells (negative
      control) and donor CD4+ T lymphocyte with (treatment group) or without hMSCs
      (positive control). The presence of hMSCs in target tissues and lymphoid organs
      was documented by using in vivo imaging and measuring the expression of EphB2 and
      ephrin-B2 by RTqPCR. Survival rate and GVHD score were also monitored. Tissue
      sections were obtained for histopathologic analysis. Flow cytometry was used to
      document donor T cell alloreactivity and expression of CCR5, CXCR3 and CCR7.
      ELISA was utilized to determine levels of proinflammatory cytokines, RANTES
      (CCL5) and phosphorylated STAT 5A/B. RTqPCR was performed to quantify expression
      of CCL3 and CXCL9. Western blotting was performed to qualitatively measure iNOS
      expression. RESULTS: Survival rate and GVHD score improved with hMSC treatment.
      Pathologic changes of GVHD were abrogated. Documentation of suppression of
      RANTES, CCL3, CXCL9, CCR5 and CXCR3 with simultaneous decrease of donor T cell
      alloreactivity was demonstrated 6 days after transplantation, along with
      reduction of levels of inflammatory cytokines, suppression of STAT 5A/B
      phosphorylation, increased expression of CCR7 and increased production of nitrous
      oxide by hMSCs. Documentation of homing of hMSCs to lymphoid organs and target
      tissues was also performed. CONCLUSIONS: These mechanisms contribute to the
      current understanding of MSC mechanisms of immunosuppression and forms a
      comprehensive picture of how they exert immunosuppression in an in vivo model of
      immune dysregulation.

PMID- 26000206
TI  - Global spine congress 2015.

PMID- 26000205
TI  - What Causes Eye Pain?
AB  - Eye pain is an unpleasant sensory and emotional experience including sensory
      discriminative, emotional, cognitive, and behavioral components and supported by
      distinct, interconnected peripheral and central nervous system elements. Normal
      or physiological pain results of the stimulation by noxious stimuli of sensory
      axons of trigeminal ganglion (TG) neurons innervating the eye. These are
      functionally heterogeneous. Mechano-nociceptors are only excited by noxious
      mechanical forces. Polymodal nociceptors also respond to heat, exogenous
      irritants, and endogenous inflammatory mediators, whereas cold thermoreceptors
      detect moderate temperature changes. Their distinct sensitivity to stimulating
      forces is determined by the expression of specific classes of ion channels:
      Piezo2 for mechanical forces, TRPV1 and TRPA1 for heat and chemical agents, and
      TRPM8 for cold. Pricking pain is evoked by mechano-nociceptors, while polymodal
      nociceptors are responsible of burning and stinging eye pain; sensations of
      dryness appear to be mainly evoked by cold thermoreceptors. Mediators released by
      local inflammation, increase the excitability of eye polymodal nociceptors
      causing their sensitization and the augmented pain sensations. During chronic
      inflammation, additional, long-lasting changes in the expression and function of
      stimulus-transducing and voltage-sensitive ion channels develop, thereby altering
      polymodal terminal's excitability and evoking chronic inflammatory pain. When
      trauma, infections, or metabolic processes directly damage eye nerve terminals,
      these display aberrant impulse firing due to an abnormal expression of
      transducing and excitability-modulating ion channels. This malfunction evokes
      'neuropathic pain' which may also result from abnormal function of higher brain
      structures where ocular TG neurons project. Eye diseases or ocular surface
      surgery cause different levels of inflammation and/or nerve injury, which in turn
      activate sensory fibers of the eye in a variable degree. When inflammation
      dominates (allergic or actinic kerato-conjunctivitis), polymodal nociceptors are
      primarily stimulated and sensitized, causing pain. In uncomplicated
      photorefractive surgery and moderate dry eye, cold thermoreceptors appear to be
      mainly affected, evoking predominant sensations of unpleasant dryness.

PMID- 26000207
TI  - A markov model approach assessing the cost of illness of generalized anxiety
      disorder in Canada.
AB  - INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic disease with waxing
      and waning of symptoms. This is the first comprehensive economic model developed
      to reflect the nature and course of GAD. METHODS: An incidence-based
      probabilistic Markov model was developed reflecting nine GAD health states (HS):
      clinical assessments (three HS), maintenance therapies (four HS), discontinuation
      (one HS), and death (one HS). A probability curve of the GAD onset (ages 18-80)
      determined entry into the model and assumed patients retained the diagnoses until
      death. Canadian Psychiatric Association (CPA) guidelines determined
      pharmacotherapy, with revisions/validation by an expert panel. Direct costs
      (clinician, pharmacotherapy, hospitalization) were retrieved from government
      publications. Remission was based on pooled-analysis of CPA-cited evidence.
      Remaining clinical rates, absenteeism, and hospitalization were retrieved from
      the literature. Direct costs were attributed throughout the model except for the
      discontinuation and death HS. Indirect costs (wage rate) were retrieved from
      government publications and the literature (absenteeism), and were attributed to
      patients with GAD <=65 years of age. Results were discounted at 5% and results
      expressed in 2008 Canadian dollars. RESULTS: The mean lifetime cost of illness
      (COI) was estimated to be $31,213 (SD $9,100) per patient. The cost of
      absenteeism accounted for 96% of the mean COI. The mean age of onset was 31 years
      and approximately 19% did not respond to pharmacotherapy. Over 85% of patients
      discontinued treatment by the fourth cycle (2nd year of therapy). Over the course
      of the model, a mean of 53% of patients relapsed, with an average rate of 0.79
      relapses per patient. On average and over a lifetime, the disorder went unmanaged
      over a period of 14 (SD 9) years. The model was most sensitive to absenteeism.
      CONCLUSION: GAD is a costly disease with a lifetime COI <$32k/patient, with
      absenteeism exerting a significant impact.

PMID- 26000208
TI  - The Human Body's Own Language to be Considered for Safe and Effective
      Neurostimulation.
AB  - INTRODUCTION: The general objective of this study was to provide an improved
      software for safer and more effective neurostimulation therapy. MATERIALS AND
      METHODS: Tulgar implants, employing combined modulation of stimulation
      synchronized with heart rate, breathing frequency, and position of the patient
      (HBP), were applied as vagus nerve stimulation (VNS) for the management of
      refractory epilepsy in 105 patients who were followed up for 1 year. RESULTS:
      Fifty-nine out of 105 (56.19%) patients were seizure free, 34 (32.38%) patients
      had partial improvement in quality of life with a decrease in intensity and
      frequency of the seizures, and 12 (11.43%) patients did not respond to
      stimulation. DISCUSSION: Other similar studies, undertaken with non-Tulgar
      equipment, reported a 10% full recovery, 60% partial improvement in quality of
      life, and 30% zero response. Comparisons of these results reveal an approximate
      fivefold increase in seizure freedom, and threefold decrease in the number of
      nonresponsive patients. CONCLUSIONS: The findings of the present study imply that
      HBP-modulated mode of stimulation could be safer and more effective in
      neurostimulation, at least in VNS.

PMID- 26000209
TI  - Virtual reality versus conventional treatment of reaching ability in chronic
      stroke: clinical feasibility study.
AB  - INTRODUCTION: The objective of this study was to evaluate the potential of
      exercises performed in a 2D video-capture virtual reality (VR) training
      environment to improve upper limb motor ability in stroke patients compared to
      those performed in conventional therapy. METHODS: A small sample randomized
      control trial, in an outpatient rehabilitation center with 12 patients with
      chronic stroke, aged 33-80 years, who were randomly allocated to video-capture VR
      therapy and conventional therapy groups. All patients participated in four
      clinical evaluation sessions (pre-test 1, pre-test 2, post-test, follow-up) and
      nine 45-minute intervention sessions over a 3-week period. Main outcomes assessed
      were Body Structure and Function (impairment: Fugl-Meyer Assessment [FMA];
      Composite Spasticity Index [CSI]; Reaching Performance Scale for Stroke),
      Activity (Box and Blocks; Wolf Motor Function Test [WMFT]), and Participation
      (Motor Activity Log) levels of the International Classification of Functioning.
      RESULTS: Improvements occurred in both groups, but more patients in the VR group
      improved upper limb clinical impairment (FMA, CSI) and activity scores (WMFT) and
      improvements occurred earlier. Patients in the VR group also reported
      satisfaction with the novel treatment. CONCLUSIONS: The modest advantage of VR
      over conventional training supports further investigation of the effect of video
      capture VR or VR combined with conventional therapy in larger-scale randomized,
      more intense controlled studies.

PMID- 26000210
TI  - The impact of spina bifida on caregivers.
AB  - INTRODUCTION: Neural tube defects (NTDs) are the second most common birth
      defects. Spina bifida (SB) and anencephaly make up approximately 90% of total
      NTDs. Given the number of infants born with an NTD each year, anyone who provides
      unpaid care for the child (especially caregivers) is affected. This literature
      review explores the humanistic burden on caregivers of people with SB,
      specifically myelomeningocele. METHODS: A search using PubMed, PsycINFO, and
      Embase was performed to find studies from 1976 to 2010. Interpretative
      phenomenological analysis was performed on qualitative data and relevant extracts
      from the data were collated to form master themes. RESULTS: A total of 168
      abstracts met the inclusion and exclusion criteria. Of these, 25 articles related
      to caregivers of individuals with SB. Four master themes emerged: initial
      diagnosis, living with an individual with SB, social support, and coping.
      Different aspects of caregivers' lives were found to be affected by caring for a
      child with SB, including activities of daily living, work impact, time
      consumption, parental responsibilities, confidence, feelings and emotions, mental
      health, stress, social impact, psychological adjustment, and relationships.
      CONCLUSION: NTDs, such as SB, present a multitude of issues to caregivers. Issues
      that affect caregivers of individuals with SB must be addressed in order to
      reduce the considerable burden that SB places on the caregiver. Continued and
      enhanced support from health services and patient advocacy groups is needed. For
      example, providing additional information, support, and empathy can help parents
      prepare themselves for dealing with the needs of a child with SB over their
      lifetime.

PMID- 26000211
TI  - Effect of tetrabenazine on motor function in patients with huntington disease.
AB  - INTRODUCTION: Tetrabenazine (TBZ) reduces chorea related to Huntington disease
      (HD); however, it is uncertain whether this effect improves functionally relevant
      motor skills such as hand coordination and balance. The objective of this study
      was to provide pilot data regarding three motor function tests, which might be
      useful in monitoring symptom progression and therapeutic response, pending formal
      validation. METHODS: The authors assessed 11 ambulatory patients with HD-related
      chorea on two occasions: (1) while off TBZ (either prior to starting therapy or
      following a >24 h washout) and (2) when on a stable dose of TBZ, titrated to
      optimal effect. Study evaluations included the Jebsen-Taylor Hand Function Test
      (JTHFT) and Berg Balance Scale, a timed 25-foot walk, the Montreal Cognitive
      Assessment (MoCA) and the complete United Huntington Disease Rating Scale
      (UHDRS). RESULTS: Maximal chorea scores (UHDRS item 12) improved from 11.1 +/-
      2.9 to 8.5 +/- 3.9 while on TBZ (P = 0.03), but we could not detect an
      improvement in functional measures while on TBZ in this small cohort. Scores of
      the JTHFT were globally slower than published normative data and correlated with
      MoCA summary scores, but not UHDRS chorea scores. CONCLUSIONS: This pilot study
      did not detect significant functional gains with chorea suppression. The fact
      that performance on tests of hand function correlates with MoCA but not UHDRS
      chorea scores highlights the need for additional treatments targeted toward the
      cognitive aspects of HD.

PMID- 26000212
TI  - A review of the social, psychological, and economic burdens experienced by people
      with spina bifida and their caregivers.
AB  - INTRODUCTION: Despite measures to reduce the incidence of neural tube defects
      (NTDs), the rate of decline has not been as dramatic as expected. At least
      300,000 newborns worldwide are known to be affected by NTDs each year. This
      comprehensive literature review summarizes the human and economic burden of NTDs
      to patients and caregivers, with particular focus on spina bifida (SB). METHODS:
      PubMed, PsycINFO, and Embase were searched for studies from January 1976 to
      November 2010 that included clinical terms, such as NTD, and at least one patient
      reported outcome or cost term. A conceptual model was also developed. RESULTS:
      Areas of peoples' lives affected by SB included physical and role functioning,
      activities of daily living, bodily pain, vitality, emotional functioning, mental
      health, self-esteem, self-image, social functioning, relationships, and sexual
      functioning. Areas of caregivers' lives affected included activities of daily
      living, work impact, time consumption, parental responsibilities (including
      responsibilities to other children), confidence, feelings and emotions, mental
      health, stress, social impact, psychological adjustment, relationships (with SB
      child, siblings, other family members), social support, coping strategies, and
      termination decisions. Cost burdens on patients and caregivers also include out
      of-pocket costs, lost wages, or household production due to increased morbidity
      and mortality, transportation and other nonmedical costs. CONCLUSIONS: This
      review highlights the need to provide care and support to individuals with SB and
      their caregivers. Results also emphasize the importance of effective long-term
      public health campaigns and/or newer strategies to prevent NTDs, such as SB.

PMID- 26000213
TI  - Perampanel: What is its Place in the Management of Partial Onset Epilepsy?
AB  - INTRODUCTION: Current pathways for treatment of partial onset epilepsy are
      diverse and include 14 new antiepileptic drugs (AEDs) licensed for use as either
      monotherapy or adjunctive therapy. However, the impact of these new AEDs on the
      treatment of partial epilepsy has so far been disappointing and there persists a
      need for additional drugs. Recently, perampanel, a first-in-class AED was
      licensed as an adjunct for the management of refractory partial onset seizures
      with or without secondary generalization in patients 12 years and older. This
      review highlights the current management of partial epilepsy and analyses the
      published clinical and preclinical data of perampanel to consider its potential
      role in the treatment of partial epilepsy. METHODS: A literature review of
      Embase, Medline and PubMed was conducted in April 2013 using the search terms
      'perampanel' and 'AMPA receptor antagonist/blocker'. Publications were included
      if they discussed perampanel in the context of preclinical or clinical epilepsy.
      RESULTS: Perampanel acts on the glutamate pathway. It is a novel highly selective
      non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptor antagonist. This is a previously untargeted post-synaptic glutamate
      receptor. It is responsible for mediating rapid trans-synaptic signal
      transduction and hence believed to play a major role in seizure propagation. The
      three pivotal placebo-controlled trials of adjunctive perampanel demonstrated
      that the effective dosing range is 4-12 mg/day. The drug can be prescribed once
      daily, and its adverse effect profile is minimal with dizziness, fatigue,
      headache, and somnolence being the most commonly reported. CONCLUSIONS:
      Perampanel is a welcome addition as it represents an alternative approach in the
      management of epilepsy with potential to have a significant impact on the
      prognosis of intractable epilepsy. However, it has only recently been licensed
      for clinical use in Europe, the USA, and Canada, and there are no data directly
      comparing it with other AEDs; hence, it remains far too early to ascertain its
      place in the treatment of patients with partial epilepsy.

PMID- 26000214
TI  - Quality of Life in Depressed Patients in UK Primary Care: The FINDER Study.
AB  - OBJECTIVES: To investigate the impact of depression and its treatment on health
      related quality of life (HRQoL) in a naturalistic, primary care setting in the
      UK. METHODS: The Factors Influencing Depression Endpoints Research (FINDER) study
      was a European, 6-month, prospective, observational study designed to estimate
      HRQoL in patients with a clinical diagnosis of depression. This paper examines
      primary care patients recruited in the UK. HRQoL was measured at baseline and at
      3 and 6 months after starting antidepressant therapy using the Short Form 36
      Health Status Survey and the European Quality of Life-5 Dimensions (EQ-5D).
      Regression analysis was used to identify baseline and treatment variables
      independently and significantly associated with HRQoL. Further analyses included
      the effect of caseness for depression on HRQoL, the effect of moderate/severe
      pain at baseline on HRQoL, changes in overall pain, pain interference scores, and
      the use of different antidepressants by pain cohort. RESULTS: A total of 608
      patients was recruited from 58 centres and mean HRQoL was significantly below
      reported population norms at baseline. Most improvement in HRQoL was seen at 3
      months for EQ-5D, with small additional improvement at 6 months. Worse HRQoL
      outcomes at 6 months were associated with higher somatic symptoms score, duration
      of depression at baseline, and switching within antidepressant classes. Patients
      meeting the criteria for caseness for depression, or with significant pain at
      baseline showed less improvement in HRQoL scores at 6 months. CONCLUSION:
      Patients presenting with depression in primary care show reduced HRQoL compared
      to population norms. HRQoL improves during antidepressant treatment particularly
      within the first 3 months. Nonpainful somatic symptoms, socioeconomic factors,
      depression variables and switching within antidepressant class predict poor HRQoL
      outcome. Pain is a common symptom in depressed patients and remains after 6
      months' treatment. Pain and somatic symptoms should be assessed in all patients
      with depression in primary care.

PMID- 26000215
TI  - Social characteristics and quality of life of portuguese multiple sclerosis
      patients.
AB  - INTRODUCTION: Few studies have analyzed the importance of socio-demographic
      variables on the perception of health-related quality of life (HRQoL) in patients
      with multiple sclerosis (MS). METHODS: The sample was composed of 150 patients
      with MS. Statistical analysis was performed using Mann-Whitney U and Kruskal
      Wallis H non-parametric tests comparing socio-demographic items with HRQoL.
      RESULTS: We found statistically significant differences between age, education
      levels, employment status, disability and all dimensions of HRQoL. DISCUSSION:
      This study contributes to a more systematic knowledge about the relationship
      between social characteristics and HRQoL, which is important to improve the
      planning of health care in MS patients. CONCLUSION: We found that younger
      patients, those with higher education level, those who were employed, and with
      lower disease progression and lower disability, had better HRQoL.

PMID- 26000216
TI  - Bilateral acute angle-closure glaucoma following treatment with topiramate for
      headache.
AB  - INTRODUCTION: This case report adds supportive evidence to the development of
      acute angle-closure glaucoma (AACG), a rare but serious adverse effect following
      the use of topiramate (TPM) for a severe headache. CASE REPORT: A 25-year-old
      female reported with severe headache, suspected to be migraine, and was started
      on TPM 25 mg/day on the first day. However, she presented at the emergency clinic
      of a hospital with sudden blurring of vision and colored halos 5 days after
      stopping the drug, i.e., day 8. She was subjected to ophthalmic examination and
      was diagnosed with AACG. The intraocular pressure (IOP) was found to be elevated
      and she was hence started on acetazolamide 500 mg instantly, maintained on tablet
      acetazolamide 250 mg four times a day (QID), pilocarpine 2% eye drops QID,
      travoprost 0.004% once a day (OD), and dorzolamide 2% eye drops three times a day
      (TID). After a week's treatment, there was rapid improvement with return of IOP
      to normal. CONCLUSION: TPM-induced AACG is a rare serious adverse event leading
      to blindness but is preventable, when diagnosed early and by instituting
      appropriate treatment.

PMID- 26000217
TI  - Listeria monocytogenes Meningoencephalitis Mimicking Stroke in a Patient with
      Chronic Lymphocytic Leukemia.
AB  - INTRODUCTION: Listeria monocytogenes is an important opportunistic pathogen
      affecting patients with immunosuppression and shows a high tropism for the
      central nervous system. The clinical manifestations of central nervous system
      listerial infections are variable and represent a diagnostic challenge. CASE
      REPORT: The authors report the case of a 59-year-old woman who was admitted for
      confusion, agitation, and right-lower extremity weakness. The patient was treated
      for 3 months with fludarabine and 2 months with corticosteroids for chronic
      lymphocytic leukemia and hemolytic anemia, respectively. At the time of
      admission, the neurological examination revealed grade 4 right-lower extremity
      weakness with reflex asymmetry and right-sided Babinski sign; no signs of
      meningeal irritation were detectable. Physical examination was notable for grade
      1 obesity and subfebrility. The cerebral computed tomography scan demonstrated a
      hypodense lesion in the left frontal lobe. Cerebral magnetic resonance imaging
      revealed a hyperintense lesion in the left frontal lobe with extension toward the
      basal ganglia (T2 and Fluid-Attenuated Inversion Recovery [FLAIR] sequences), and
      small nodular enhancing lesions after gadolinium infusion in the affected
      territory. Blood analyses revealed pancytopenia and elevated liver enzymes.
      During the second day after admission, the patient developed fever and
      neurological examination revealed signs of meningeal irritation. The
      cerebrospinal fluid (CSF) analyses revealed: red blood cells 24 cells/mm(3);
      white blood cells 829 cells/mm(3) (76% lymphocytes, 22% neutrophils, 2%
      monocytes); protein level 111.2 mg/dL; glucose level 10.2 mg/dL. Empiric anti
      infection treatment was started with intravenous ceftriaxone, ciprofloxacine,
      aciclovir, and fluconasole. Both blood cultures and CSF cultures were positive
      for L. monocytogenes. The antimicrobial regimen was changed to ampicillin. The
      clinical and imaging outcome was excellent. CONCLUSION: The supratentorial focal
      lesions secondary to Listeria meningoencephalitis are rare. The cases with focal
      neurological signs without fever at onset can resemble stroke.

PMID- 26000218
TI  - Childhood absence epilepsy successfully treated with the paleolithic ketogenic
      diet.
AB  - INTRODUCTION: Childhood absence epilepsy is an epilepsy syndrome responding
      relatively well to the ketogenic diet with one-third of patients becoming seizure
      free. Less restrictive variants of the classical ketogenic diet, however, have
      been shown to confer similar benefits. Beneficial effects of high fat, low
      carbohydrate diets are often explained in evolutionary terms. However, the
      paleolithic diet itself which advocates a return to the human evolutionary diet
      has not yet been studied in epilepsy. RESULTS: Here, we present a case of a 7
      year-old child with absence epilepsy successfully treated with the paleolithic
      ketogenic diet alone. In addition to seizure freedom achieved within 6 weeks,
      developmental and behavioral improvements were noted. The child remained seizure
      free when subsequently shifted toward a paleolithic diet. CONCLUSION: It is
      concluded that the paleolithic ketogenic diet was effective, safe and feasible in
      the treatment of this case of childhood absence epilepsy.

PMID- 26000219
TI  - Rasagiline and rapid symptomatic motor effect in Parkinson's disease: review of
      literature.
AB  - Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in
      addition to levodopa in the treatment of Parkinson's disease. Once daily
      administration of rasagiline makes it easy to use, and allows good compliance by
      patients and adherence to therapy. Several multicenter studies have noted the
      effectiveness of rasagiline on both motor and non-motor symptoms, which require a
      complex pharmacologic approach, such as cognitive disorders. A recent study also
      reported a rapid action of rasagiline on motor symptoms. Positive findings have
      been highlighted by an economic model study. This review analyzes the main
      studies of rasagiline, with particular attention to the effectiveness of the drug
      on motor symptoms. 

PMID- 26000220
TI  - Mexazolam: clinical efficacy and tolerability in the treatment of anxiety.
AB  - INTRODUCTION: Mexazolam is indicated for the management of anxiety with or
      without psychoneurotic conditions. In adult patients, the recommended daily
      dosage of mexazolam is 1-3 mg, administered three times daily. The objective of
      this article is to review the available information on the benzodiazepine (BZD)
      mexazolam and its clinical utility in treating patients with anxiety. METHODS:
      The PubMed database was searched using the keyword "mexazolam" with no date or
      language restrictions applied to the search. As only 11 papers were retrieved,
      some previously published manuscripts of interest known by the authors (not
      indexed on PubMed) have been added for completeness. Relevant information was
      selected for inclusion by the authors. RESULTS: A number of early studies
      demonstrated the ability of mexazolam to reduce anxiety symptoms with few side
      effects in patients with disorders associated with anxiety. Following on from
      this preliminary evidence, controlled studies directly comparing mexazolam with
      other BZDs showed that the drug is more effective than bromazepam and oxazolam,
      and is at least as effective as alprazolam. A larger, multicenter, phase IV study
      also showed that mexazolam 2 or 3 mg/day rapidly improved Hamilton Anxiety Rating
      Scale scores and substantially reduced the frequency and severity of numerous
      somatic anxiety symptoms in patients with anxiety disorders. With regard to
      safety, the clinical evidence indicates that mexazolam is generally well
      tolerated, with a low incidence of drowsiness and sedation. Furthermore, the lack
      of psychomotor or cognitive performance impairment following mexazolam
      administration may lead to better treatment compliance. CONCLUSION: The available
      clinical evidence suggests that mexazolam is an effective therapeutic option for
      the management of anxiety. However, larger, well-controlled clinical trials are
      needed to directly compare and contrast mexazolam's efficacy and safety with
      other BZDs.

PMID- 26000221
TI  - Review of Dextromethorphan 20 mg/Quinidine 10 mg (NUEDEXTA((r))) for Pseudobulbar
      Affect.
AB  - Pseudobulbar affect (PBA) is a dysfunction of emotional expression characterized
      by involuntary outbursts of crying or laughing disproportionate or unrelated to
      mood, occurring in patients with various underlying neurologic disorders. This
      review describes the clinical data supporting dextromethorphan (DM) hydrobromide
      combined with quinidine sulfate (Q) as treatment of PBA and briefly surveys the
      ongoing debates concerning the terminology for dysfunction of emotional
      expression, as well as the ongoing searches for its brain substrates. Until
      recently, pharmacologic intervention consisted chiefly of off-label
      antidepressants. In October 2010, however, DM/Q at 20/10 mg twice daily received
      approval from the United States Food and Drug Administration for PBA in any
      setting, and in June 2013, dosages of 20/10 and 30/10 mg twice daily (labeled as
      15/9 and 23/9 mg, respectively, DM/Q base) received approval from the European
      Medicines Agency. DM is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate
      receptor antagonist, a sigma-1 receptor agonist, and a serotonin and
      norepinephrine reuptake inhibitor. To block DM hepatic metabolism, thereby
      increasing DM bioavailability, Quinidine, a cytochrome P450 2D6 inhibitor, is
      coadministered at a dosage well below those for treating cardiac arrhythmia.
      Three large-scale DM/Q trials have utilized PBA-episode counts and the Center for
      Neurologic Study-Lability Scale (CNS-LS), a validated PBA rating scale, to
      measure efficacy. In a 4-week study of patients with PBA in amyotrophic lateral
      sclerosis (ALS), DM/Q 30/30 mg was superior to its component drugs. A 12-week,
      double-blind, placebo-controlled study of DM/Q 30/30 mg showed similar efficacy
      in patients with PBA in multiple sclerosis (MS). A subsequent 12-week study of
      patients with PBA and ALS or MS showed superiority to placebo for the 20/10 and
      30/10 mg doses. Efficacy was maintained during a 12-week, open-label extension
      (30/10 mg dose), with further improvement of mean CNS-LS scores. Across these
      studies, DM/Q was generally safe and well tolerated, with no evidence of
      clinically relevant cardiac or respiratory effects. DM/Q is being studied
      (currently unapproved) for conditions including agitation in autism and in
      dementia. 

PMID- 26000222
TI  - Laquinimod therapy in multiple sclerosis: a comprehensive review.
AB  - INTRODUCTION: Multiple sclerosis (MS) is considered an autoimmune disease with
      inflammatory and neurodegenerative underlying processes that affect the central
      nervous system. The available disease-modifying therapies (DMTs) approved to
      treat MS have only shown partial benefit in controlling the disease progression,
      primarily impeding its inflammatory component, while the parenteral
      administration of most of these therapies has shown to affect patient compliance.
      Laquinimod is a promising new oral drug recently evaluated in a third phase III
      clinical trial that demonstrated beneficial effects in delaying disease
      progression and preventing brain atrophy, suggesting a potential neuroprotective
      effect and a favorable safety profile. AREAS COVERED: This is a comprehensive
      review covering clinical efficacy and safety data obtained from two phase III
      clinical trials, as well as the presumed beneficial mechanism of action, of
      laquinimod. This article also provides a short overview of the oral DMTs recently
      approved for the treatment of relapsing MS, as well as challenges that still
      remain to be overcome to fully control the relentless course of MS. CONCLUSION:
      Laquinimod has been shown to have a novel immunomodulatory and potential
      neuroprotective mechanism of action as suggested from animal models and in vitro
      experimental data. Phase III clinical trials ALLEGRO (Clinicaltrials.gov
      #NCT00509145) and BRAVO (Clinicaltrials.gov #NCT00605215) have demonstrated
      clinical efficacy and tolerability, while the third phase III study is currently
      evaluating the safety and efficacy of laquinimod at a higher dosage. Emerging
      oral treatments like laquinimod will provide new options for patients to consider
      that can lead to better patient adherence and improved outcomes.

PMID- 26000223
TI  - Chronic Treatment with the 5-HT1A Receptor Partial Agonist Tandospirone Increases
      Hippocampal Neurogenesis.
AB  - INTRODUCTION: A large-scale clinical trial, the Sequence Trial Alternatives to
      Relieve Depression (STAR*D) study, concluded that about one-third of the studied
      patients with major depressive disorder remitted during the initial treatment
      with selective serotonin reuptake inhibitors and that approximately half of the
      remitted subjects relapsed over a 1-year follow-up. The development of new
      therapeutic approaches with potent efficacy and good tolerability for the
      treatment of depressive disorders is of great importance. Adult hippocampal
      neurogenesis has been proposed to be important for understanding and treating
      depression and anxiety. The present study aimed to elucidate whether or not 5
      hydroxytryptamine 1A (5-HT1A) receptor partial agonists have a potential
      therapeutic effect for the treatment of depressive and anxiety disorders, from
      the standpoint of neurogenesis. METHODS: Male Sprague-Dawley rats were
      subcutaneously administered a vehicle or tandospirone (TDS) (1 or 10 mg/kg) once
      daily for 14 days. The effects of chronic TDS treatment on neurogenesis were
      evaluated on the day after the last injection. The quantification of hippocampal
      neurogenesis was estimated using immunostaining with doublecortin (DCX), a marker
      protein of newborn neurons. RESULTS: Chronic TDS treatment resulted in a
      significant increase in the number of DCX-positive cells per volume of dentate
      gyrus in a dose-dependent manner. CONCLUSION: The results strongly suggest that 5
      HT1A receptor partial agonists would be useful and beneficial in the treatment of
      depressive and anxiety disorders through increased hippocampal neurogenesis.

PMID- 26000224
TI  - Florbetaben for PET Imaging of Beta-Amyloid Plaques in the Brain.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting
      the elderly. Current clinical diagnostic tools are often ineffective in
      accurately diagnosing AD. However, new advances in diagnostic imaging,
      particularly positron emission tomography (PET) amyloid imaging, have shown
      increased sensitivity and specificity, as well as high inter-reader agreement.
      The most commonly studied tracer, PiB-C11, has shown high affinity binding to
      amyloid, but is limited in its use outside of research due to its short half
      life. Instead, development of other PET ligands with increased half-life, such as
      fluorine-18-labeled ((18)F) tracers, allows for more widespread use of PET in
      clinical settings. In particular, recent phase II and III trials of (18)F
      florbetaben have demonstrated the high accuracy of this PET tracer in identifying
      amyloid accumulation. This paper will examine the techniques of amyloid imaging,
      focusing particularly on the recently approved (18)F-florbetaben. 

PMID- 26000225
TI  - Relapsing-remitting multiple sclerosis: patterns of response to disease-modifying
      therapies and associated factors: a national survey.
AB  - INTRODUCTION: Current treatments for relapsing-remitting multiple sclerosis
      (RRMS) are only partially effective. The objective of this study was to
      characterize treatment response in RRMS patients in Portugal to 12-month therapy
      with first-line disease-modifying therapies. METHODS: In this retrospective
      study, neurologists at participating centers completed survey questionnaires
      using records of patients with RRMS who had received first-line treatment with
      one of five European Medicine Agency-approved agents in the 12 months prior to
      inclusion in the survey. Sub-optimal responders included patients treated for at
      least 1 year, and who had >=1 relapse(s) or an increase of 1.5 points on the
      Expanded Disability Status Scale (EDSS; if baseline EDSS was 0) or an increase of
      >=0.5 points (baseline EDSS >=1). Optimal responders included patients treated
      for at least 1 year without relapse and who had an increase of <1.5 points on
      EDSS (if baseline EDSS was 0) or no increase in EDSS (baseline EDSS >=1).
      RESULTS: Data for 1,131 patients from 15 centers were analyzed. Twenty-six
      percent (95% confidence interval 23-28%) of patients had sub-optimal treatment
      response. Duration of therapy (P < 0.001), age at the start of therapy (P =
      0.03), and baseline EDSS score (P < 0.001), were significantly different among
      treatments. Sub-optimal treatment response appeared to be related only to a more
      severe EDSS score at baseline and did not differ among therapies. CONCLUSION:
      Neurologists should closely monitor patients to optimize treatment strategies and
      better control disease, improving prognosis.

PMID- 26000226
TI  - Post hoc analysis of nutritional status in patients with transthyretin familial
      amyloid polyneuropathy: impact of tafamidis.
AB  - INTRODUCTION: Gastrointestinal symptoms are common among patients with
      transthyretin familial amyloid polyneuropathy (TTR-FAP). This post hoc analysis
      evaluated the nutritional status of TTR-FAP patients treated with tafamidis while
      enrolled in clinical trials. METHODS: Nutritional status was measured by the
      modified body mass index (mBMI = BMI * albumin level). Treatment-related changes
      in mBMI were reported for 71 Val30Met TTR-FAP patients who completed an 18-month,
      randomized, double-blind, placebo-controlled trial and who continued into its
      open-label, 12-month extension. RESULTS: At month 18, mBMI worsened in the
      placebo group (n = 33) (-33 +/- 16 kg/m(2) g/l, P = 0.04 versus baseline) but
      improved in the tafamidis group (n = 38) (+37 +/- 14 kg/m(2) g/l, P = 0.01 versus
      baseline) such that the effect size between the groups was statistically
      significant (P = 0.001). By month 30 (completion of the open-label extension),
      placebo patients with 12 months of tafamidis treatment and tafamidis-treated
      patients with 30 months of treatment both tended to increase their mBMI (28 +/-
      19 kg/m(2) g/l and 16 +/- 18 kg/m(2) g/l, respectively). Increase in BMI was most
      pronounced in patients with low BMI at entry into the studies. CONCLUSIONS: mBMI
      is well suited to monitor disease progression in TTR-FAP patients. The delay in
      neurological deterioration brought about by tafamidis treatment in clinical
      trials is associated with improvements in, or maintenance of, mBMI. FUNDING: This
      study was sponsored by Pfizer Inc., New York, USA.

PMID- 26000227
TI  - The HV3 Score: A New Simple Tool to Suspect Cognitive Impairment in Multiple
      Sclerosis in Clinical Practice.
AB  - INTRODUCTION: Cognitive impairment in multiple sclerosis (MS) is common even in
      the early stages of the disease. Our objective was to improve early detection of
      cognitive impairment in MS. METHODS: Seventy-five patients with relapsing
      remitting (RR) MS and 20 controls were enrolled. Two RRMS groups were defined
      according to their results at the Paced Auditory Serial Addition Test (PASAT).
      Patients with a z score below two standard deviations were considered impaired.
      We quantified T2 and T1 lesion volumes, and cerebral white and grey matter
      volumes on a conventional brain magnetic resonance imaging (MRI) scan. Global
      brain atrophy was evaluated using the third ventricle (V3) width (in mm). An
      average brain model was built based on controls and compared with the patient's
      MRI to quantify regional volumetric changes. RESULTS: Sixteen (21.3%) patients
      with RRMS had low PASAT performance. They had a higher Expanded Disability Status
      Scale (EDSS) score (P = 0.019). T2 and T1 lesion volumes, and grey and white
      matter volumes were the same in both groups. An enlargement of the V3 width was
      observed in the low performer group (P = 0.044) and V3 width was correlated with
      the PASAT score (r = -0.271; P = 0.021). A composite score, named HV3, was
      obtained by adding the EDSS and V3 width (in mm) and correlated with the PASAT (r
      = -0.325; P = 0.006). A cutoff HV3 score of over 5.5 identified patients with low
      PASAT performance, with a positive predictive value of 92.5% and an accuracy of
      70.1%. Focal atrophy was detected in the supplementary motor area, the cingulate
      gyrus, the right thalamus, and the inferior parietal lobules of patients with
      lower PASAT performance. CONCLUSION: Specific brain morphological changes,
      including an enlargement of the V3 width, are associated with low PASAT
      performance in patients with RRMS. The HV3 score is an additional and
      complementary tool, accessible in clinical practice, to suspect easily cognitive
      impairment in patients with RRMS and to better identify patients requiring a
      complete cognitive assessment.

PMID- 26000228
TI  - A prospective study of patients with brain MRI showing incidental t2
      hyperintensities addressed as multiple sclerosis: a lot of work to do before
      treating.
AB  - INTRODUCTION: With the development of magnetic resonance imaging (MRI) and
      publications about radiologically isolated syndrome (RIS), a lot of patients are
      referred to multiple sclerosis (MS) tertiary centers to confirm diagnosis of RIS
      or MS when brain T2 abnormalities are identified, whatever their characteristics.
      We evaluate prospectively the occurrence of RIS or MS and sensitivity,
      specificity and predictive value of McDonald criteria in diagnosis for patients
      presenting with incidental brain MRI T2 lesions. METHODS: The authors ran
      standardized procedures on 220 consecutive patients addressed by general
      practitioners or neurologists to confirm RIS or MS diagnosis on brain MRI and
      give a therapeutic advice. All patients underwent neurological tests, extensive
      blood screening, cerebrospinal fluid (CSF) examination, visual evoked potential
      (VEP) and follow-up MRI after 3, 6, 12 and 24 months to consider dissemination in
      time and space. RESULTS: Patient characteristics were: 165 women and 55 men, mean
      age: 42.7 years old (23-59). The major symptom motivating MRI was headaches
      (39%), sensitive atypical manifestations or pain (12%), mood disorders (10%),
      transient visual symptoms (9%), fatigue (8%), hormonal screening (6%), vertigo
      (6%), cranial trauma (5%), and dummy run for clinical study (5%). After a
      structured analysis of T2 lesions, the suspected diagnosis was: inflammatory
      disease 45%, vascular 33%, non-pathological 19%, genetic 2%, and metabolic 1%.
      Extensive screening confirmed the proposed diagnosis in 97% of cases. Among all
      the 220 proposed RIS patients, only 35.4% fulfilled the 2010 McDonald criteria,
      and 8% can be categorized as RIS. Dissemination in time criteria was present for
      82.7% of MS patients and 36% of RIS patients but none of the vascular or non
      pathological T2 abnormalities. CONCLUSION: Even if RIS was initially suspected on
      MRI, only a third of the patients had an inflammatory disease. Most of the
      patients had either non-specific T2 lesions or a non-inflammatory disease. Others
      were initially well categorized but had experienced clinical symptoms that could
      possibly be considered as a first clinical event. Overdiagnosis of MS can lead to
      propose an inappropriate disease-modifying therapy.

PMID- 26000229
TI  - Pregnancy outcomes following maternal and paternal exposure to teriflunomide
      during treatment for relapsing-remitting multiple sclerosis.
AB  - INTRODUCTION: Teriflunomide, indicated for the treatment of relapsing-remitting
      multiple sclerosis, is contraindicated in pregnancy based on signs of
      developmental toxicity in the offspring of rats and rabbits; developmental
      toxicity has also been observed in preclinical studies of other disease-modifying
      therapies. Despite the requirement to use reliable contraception in clinical
      trials evaluating the safety and efficacy of teriflunomide, a number of
      pregnancies have been reported. This work reports pregnancy outcomes in
      teriflunomide clinical trials. METHODS: Pregnancy outcomes were evaluated in a
      retrospective analysis of the global pharmacovigilance database. The following
      information was collected from the pharmacovigilance database or individual
      patient files: treatment allocation, pregnancy outcome, teriflunomide exposure,
      and use of the accelerated elimination procedure. RESULTS: At data cut-off, 83
      pregnancies were reported in female patients and 22 pregnancies were documented
      in partners of male patients. All newborns were healthy and did not have any
      structural or functional abnormalities at birth. CONCLUSION: Available data do
      not indicate any teratogenic signals in patients treated with teriflunomide.

PMID- 26000230
TI  - Robotic-assisted Kidney Transplantation: Our Experience and Literature Review.
AB  - Kidney transplantation is the preferred treatment for patients with end-stage
      renal disease. While open surgery remains the gold standard, minimally invasive
      surgery has recently been introduced for the recipient undergoing kidney
      transplantation. Our team has employed the robotic surgical system to perform
      renal transplantation in obese recipients to minimize the risk of surgical site
      infections, with good results in terms of complications and graft and patient
      survival. However, others groups have performed kidney transplantation
      robotically in nonobese patients using different techniques. The da Vinci
      surgical system allows the performance of kidney transplantation under optimal
      operative conditions. Larger studies and long-term follow-up of recipients are
      required to determine the effectiveness of this approach. In this article, we
      describe our experience and review the development of the robotic-assisted kidney
      transplantation (RAKT).

PMID- 26000231
TI  - Diagnosis and Treatment of Pancreas Rejection.
AB  - Despite significant improvement in pancreas allograft survival, rejection of the
      pancreas remains a major clinical problem. In addition to cellular rejection of
      the pancreas, antibody-mediated rejection of the pancreas is now a well-described
      entity. The 2011 Banff update established comprehensive guidelines for the
      diagnosis of acute and chronic AMR. The pancreas biopsy is critical in order to
      accurately diagnose and treat pancreas rejection. Other modes of monitoring
      pancreas rejection we feel are neither sensitive nor specific enough. In this
      review, we examine recent advances in the diagnosis and treatment of pancreas
      rejection as well as describe practical diagnostic and treatment algorithms.

PMID- 26000232
TI  - Socio-economic patterning of cardiometabolic risk factors in rural and peri-urban
      India: Andhra Pradesh children and parents study (APCAPS).
AB  - AIM: To assess the prevalence of cardiometabolic risk factors by socio-economic
      position (SEP) in rural and peri-urban Indian population. SUBJECTS AND METHODS:
      Cross-sectional survey of 3,948 adults (1,154 households) from Telangana (2010
      2012) was conducted to collect questionnaire-based data, physical measurements
      and fasting blood samples. We compared the prevalence of risk factors and their
      clustering by SEP adjusting for age using the Mantel Hansel test. RESULTS: Men
      and women with no education had higher prevalence of increased waist
      circumference (men: 8 vs. 6.4 %, P < 0.001; women: 20.9 vs. 12.0 %, P = 0.01),
      waist-hip ratio (men: 46.5 vs. 25.8 %, P = 0.003; women: 58.8 vs. 29.2 %, P =
      0.04) and regular alcohol intake (61.7 vs. 32.5 %, P < 0.001; women: 25.7 vs. 3.8
      %, P < 0.001) than educated participants. Unskilled participants had higher
      prevalence of regular alcohol intake (men: 57.7 vs. 38.7 %, P = 0.001; women:
      28.3 vs. 7.3 %, P < 0.001). In contrast, participants with a higher standard of
      living index had higher prevalence of diabetes (top third vs. bottom third: men
      5.2 vs. 3.5 %, P = 0.004; women 5.5 vs. 2.4 %, P = 0.003), hyperinsulinemia (men
      29.5 vs. 16.3 %, P = 0.002; women 31.1 vs. 14.3 %, P < 0.001), obesity (men 23.3
      vs. 10.6 %, P < 0.001; women 25.9 vs. 12.8 %, P < 0.001), and raised LDL (men
      16.8 vs. 11.4 %, P = 0.001; women 21.3 vs. 14.0 %, P < 0.001). CONCLUSIONS:
      Cardiometabolic risk factors are common in rural India but do not show a
      consistent association with SEP except for higher prevalence of smoking and
      regular alcohol intake in lower SEP group. Strategies to address the growing
      burden of cardiometabolic diseases in urbanizing rural India should be assessed
      for their potential impact on social inequalities in health.

PMID- 26000233
TI  - Sleep duration differences between children of migrant and native origins.
AB  - AIM: To explore whether primary school children of migrant and native Dutch
      origins differ regarding their sleep duration per night, a risk for overweight
      and obesity, and to determine to what degree differences in parenting styles
      contribute to these differences. SUBJECTS AND METHODS: A cross-sectional survey,
      including 1,943 children aged 8-9 years old and their primary caregivers, was
      performed. Data were collected from primary schools in cities and adjacent
      municipalities in The Netherlands: Eindhoven and Rotterdam. The outcome measure
      was mean sleep duration per night. The main independent variable was migrant
      background, based on the country of birth of the parents. A possible mediating
      variable was parenting style (rejecting, neglecting, permissive, authoritarian,
      authoritative). Age and sex of the child as well as parental socioeconomic
      status, as indicated by educational level, were added as confounders. RESULTS:
      Dutch children have the highest sleep duration: more than 11 h (mean = 670.1; SD
      = 27.7). All migrant children show less than 11 h of sleep per night. Migrant
      children of non-Western origin, especially Turkish and Moroccan children, show
      the lowest sleep duration per night. Parenting styles do not contribute to these
      differences. CONCLUSION: Migrant background is associated with sleep duration. As
      children of migrant origin are, in general, at higher risk for overweight and
      obesity and sleep duration is regarded as a risk factor for overweight and
      obesity, further investigation of this association is needed.

PMID- 26000235
TI  - Describing the relationship between occupational and non-occupational physical
      activity using objective measurement.
AB  - OBJECTIVE: Physical inactivity is a major health risk for working adults, yet the
      interplay between physical activity levels in work and non-work settings is not
      well understood. The association between occupational physical activity (OPA) and
      non-occupational physical activity (non-OPA), and associations by sex, were
      examined in a group of 233 working adults in the Minneapolis, MN metro area
      between 2010 and 2012. METHODS: Accelerometry-measured activity was split into
      OPA and non-OPA via participant-reported typical work start and end times.
      Regression models were used to estimate associations. RESULTS: Average weekly OPA
      was positively associated with non-OPA (B=0.18, 95% CI: 0.08-0.28) and
      associations were stronger among women than men (Binteraction = -0.39, 95% CI: 
      0.61 to -0.17). CONCLUSIONS: Results suggest that individuals with less physical
      activity during work also have less physical activity outside of work.
      Understanding the complexities of the OPA/non-OPA relationship will enable
      researchers to explore the underlying mechanisms.

PMID- 26000234
TI  - Targeting Peroxisome Proliferator-Activated Receptor-beta/delta (PPARbeta/delta)
      for Cancer Chemoprevention.
AB  - The role of peroxisome proliferator-activated receptor-beta/delta
      (PPARbeta/delta) in cancer remains contentious due in large part to divergent
      publications indicating opposing effects in different rodent and human cell
      culture models. During the past 10 years, some facts regarding PPARbeta/delta in
      cancer have become clearer, while others remain uncertain. For example, it is now
      well accepted that (1) expression of PPARbeta/delta is relatively lower in most
      human tumors as compared to the corresponding non-transformed tissue, (2)
      PPARbeta/delta promotes terminal differentiation, and (3) PPARbeta/delta inhibits
      pro-inflammatory signaling in multiple in vivo models. However, whether
      PPARbeta/delta is suitable to target with natural and/or synthetic agonists or
      antagonists for cancer chemoprevention is hindered because of the uncertainty in
      the mechanism of action and role in carcinogenesis. Recent findings that shed new
      insight into the possibility of targeting this nuclear receptor to improve human
      health will be discussed.

PMID- 26000236
TI  - Effectiveness of a Free Exercise Program in a Neighborhood Park.
AB  - BACKGROUND: Faculty, students, and alumni in a university-based kinesiology
      program developed an innovative model for health promotion practice by partnering
      with the local park administration in San Fernando, California to offer these
      exercise classes for free in a low-income, predominantly Latino neighborhood
      park. The classes were taught by students as practical training for academic
      credit. PURPOSE: To evaluate the effectiveness of this pilot program in promoting
      moderate-to-vigorous physical activity. METHODS: We used the System for Observing
      Play and Recreation in Communities (SOPARC) to assess physical activity in the
      park during the summer of 2013. We evaluated the effectiveness of the free
      classes by a within-park comparison and by comparing findings with 50 other
      parks. RESULTS: The classes substantially increased moderate-to-vigorous physical
      activities, in particular, for female park users. However, when classes were not
      offered there were no differences in park-based physical activity across parks.
      CONCLUSIONS: Active programming can increase park-based moderate-to-vigorous
      physical activity, but without programming, people may lack the motivation to
      exercise on their own. Creating a partnership between parks and kinesiology
      programs is a promising health promotion model. Replicating this type of program
      could yield important health dividends.

PMID- 26000237
TI  - ANT2-defective fibroblasts exhibit normal mitochondrial bioenergetics.
AB  - Adenine nucleotide translocase 2 (ANT2) transports glycolytic ATP across the
      inner mitochondrial membrane. Patients with ANT2 deletion were recently reported.
      We aimed at characterizing mitochondrial functions in ANT2-defective fibroblasts.
      In spite of ANT2 expression in fibroblasts, we observed no difference between
      ANT2-defective and control fibroblasts for mitochondrial respiration, respiratory
      chain activities, mitochondrial membrane potential and intracellular ATP levels.
      This indicates that ANT2 insufficiency does not alter fibroblasts basal
      mitochondrial bioenergetics.

PMID- 26000238
TI  - Ageing and Circadian rhythms.
AB  - Circadian clocks are cell-autonomous molecular feedback loops that generate daily
      rhythms in gene expression, cellular functions, physiological processes and
      behavior. The mechanisms of circadian clocks are well understood in young fruit
      flies Drosophila melanogaster, but less is known about how circadian system
      changes during organismal aging. Similar as in humans, rest/activity rhythms tend
      to weaken with age in fruit flies, suggesting conservation of aging-related
      changes in the circadian system. It has been shown that aging is associated with
      reduced expression of core clock genes in peripheral head clocks while similar
      reduction may not occur in central clock neurons regulating behavioral rhythms.
      Arrhythmic flies with mutations in core clock genes display accelerated aging and
      shortened lifespan suggesting that weakened circadian rhythms may contribute to
      aging phenotypes. To understand whether strong circadian clocks support
      organism's healthspan and lifespan, future research needs to focus on age-related
      changes in clock genes as well as clock-controlled genes in specific organs and
      tissues.

PMID- 26000240
TI  - The potential danger of flavoring in health promoting and health compromising
      products: implications for children.

PMID- 26000239
TI  - Innate Immune Responses to Nanoparticle Exposure in the Lung.
AB  - The nanotechnology revolution offers enormous societal and economic benefits for
      innovation in the fields of engineering, electronics, and medicine. Nevertheless,
      evidence from rodent studies show that biopersistent engineered nanomaterials
      (ENMs) stimulate immune, inflammatory, and fibroproliferative responses in the
      lung, suggesting possible risks for lung diseases or systemic immune disorders as
      a consequence of occupational, environmental, or consumer exposure. Due to their
      nanoscale dimensions and increased surface area per unit mass, ENMs have a much
      greater potential to reach the distal regions of the lung and generate ROS. High
      aspect ratio ENMs (e.g., nanotubes, nanofibers) activate inflammasomes in
      macrophages, triggering IL-1beta release and neutrophilic infiltration into the
      lungs. Moreover, some ENMs alter allergen-induced eosinophilic inflammation by
      immunostimulation, immunosuppression, or modulating the balance between Th1, Th2,
      and Th17 cells, thereby influencing the nature of the inflammatory response. ENMs
      also migrate from the lungs across epithelial, endothelial, or mesothelial
      barriers to stimulate or suppress systemic immune responses.

PMID- 26000241
TI  - Crisis management aspects of bam catastrophic earthquake: review article.
AB  - BACKGROUND: Bam earthquake was the most catastrophic natural disasters in recent
      years. The aim of this study was to review different aspects of crisis management
      during and after the catastrophic earthquake in Bam City, Iran. METHODS: Data
      needed for this systematic review were collected through searching PubMed, EMBASE
      and SID databases, for the period from 2003 to 2011. Keywords included
      earthquake, Iran and Bam earthquake. The data were summarized and were analyzed
      using Content Analysis. RESULTS: Out of 422 articles, 25 articles were included
      in the study. Crisis Management aspects and existing pitfalls were classified
      into seven categories including planning and organization, human resource
      management, management of logistics, international humanitarian aids, field
      performance of the military and security forces, health and medical service
      provision, and information management. Positive aspects and major pitfalls of
      crisis management have been introduced in all the mentioned categories.
      CONCLUSION: The available evidence indicated poor crisis management during Bam
      earthquake that resulted in aggravating the losses as well as diminishing the
      effect of interventions. Thus, concerning the importance of different aspects of
      the crisis management and the high prevalence of disasters in Iran, the observed
      vulnerability in disaster management process should be addressed.

PMID- 26000242
TI  - Predictors of bone mineral density in african-american and caucasian college-aged
      women.
AB  - BACKGROUND: Research regarding risk factors and prevalence of low bone mineral
      density (BMD) among African-American and Caucasian college-aged women are
      limited. The objective of this cross-sectional study was to determine if selected
      predictors of BMD in African-American and Caucasian college-aged women differ by
      race. METHODS: A total of 101 local African-American (n=50) and Caucasian (n=51)
      females, ages 18 to 30 years, were in this study. All data were collected in the
      Bone Density and Body Composition Laboratory. BMD was measured using DXA
      technology. Race, family history of osteoporosis, BMI, current physical activity,
      osteoporosis knowledge, length of time on oral contraceptives, age at menarche
      and calcium intake were included in the multiple regression analyses with spinal
      and femoral BMD as dependent variables. RESULTS: Overall, 38.6% had low spinal
      BMD and 7.9% had low femoral BMD. BMI (beta=0.073, R(2) = .148, P = .001, 95% CI
      [0.030, 0.116]) and current physical activity (beta=0.071, R(2) = .148, P = .017,
      95% CI [0.013, 0.129]) were the only variables that were statistically
      significant in predicting spinal BMD. BMI (beta=0.056, R(2) = .13, P = .010, 95%
      CI [0.014, 0.098]) and current physical activ-ity (beta=0.078, R(2) = .13, P =
      .007, 95% CI [0.022, 0.134]) were also the only varia-bles that were
      statistically significant in predicting femoral BMD. Race was not a significant
      predictor of spinal or femoral BMD. CONCLUSION: It is imperative for both African
      American and Caucasian women to engage in osteoporosis-preventive behaviors.

PMID- 26000243
TI  - Modeling the intention to choose natural vaginal delivery: using reasoned action
      and social cognitive theories.
AB  - BACKGROUND: The Behavioral Intention Model is one of the best and most widely
      models used regarding attitude of behavioral of pregnancy and decrease the rate
      of cesarean section (CS) among pregnant women, except effect of attitude and
      subjective norms on behavioral intention. Two variables of self-efficacy, and
      outcome expectation, relate to individual's behavior in an upcoming situation,
      and both of them are important at the development of behavior. The purpose of the
      present study was to develop a model to explain women's inten-tion to choose
      natural vaginal delivery (NVD). The variables of self-efficacy and outcome
      expectations, derived from Bandura's Social Cognitive Theory, and Behavioral
      Intention Model constructs were used to define the model. METHODS: The study was
      descriptive and cross-sectional in nature and took place in Pars Abad, Iran in
      2014. The non-probability sample consisted of 200 pregnant women who voluntarily
      participated in the study and provided the data. SPSS 21 and MPLUS 6.8 were
      employed to analyze the data. RESULTS: Self-efficacy, outcome expectations, and
      attitude toward NVD were associated with intention to choose the NVD. CONCLUSION:
      The study findings may play a role in designing educational interventions aimed
      at influencing the NVD and improving childbirth programs.

PMID- 26000244
TI  - Stroke education in an emergency department waiting room: a comparison of
      methods.
AB  - BACKGROUND: Since the emergency department (ED) waiting room hosts a large,
      captive audience of patients and visitors, it may be an ideal location for
      conducting focused stroke education. The aim of this study was to assess the
      effectiveness of various stroke education methods. METHODS: Patients and visitors
      of an urban ED waiting room were randomized into one of the following groups:
      video, brochure, one-to-one teaching, combination of these three methods, or
      control group. We administered a 13-question multiple-choice test to assess
      stroke knowledge prior to, immediately after, and at 1 month post-education to
      patients and visitors in the ED waiting room. RESULTS: Of 4 groups receiving
      education, all significantly improved their test scores immediately post
      intervention (test scores 9.4+/-2.5-10.3+/-2.0, P<0.01). At 1 month, the
      combination group retained the most knowledge (9.4+/-2.4) exceeding pre
      intervention and control scores (both 6.7+/-2.6, P<0.01). CONCLUSION: Among the
      various stroke education methods delivered in the ED waiting room, the
      combination method resulted in the highest knowledge retention at 1-month post
      intervention.

PMID- 26000245
TI  - Towards age-friendly hospitals in developing countries: a case study in iran.
AB  - BACKGROUND: Developing countries such as Iran are experiencing a growth in the
      elderly population. This is a challenge for healthcare providers and their
      families. This study investigated the extent in which hospitals at Tehran meet
      the criteria of age-friendly hospitals. METHODS: In this descriptive study, using
      convenience sampling, 26 hospitals were selected in Tehran, the capital city of
      Iran. The instrument was a checklist included 50 items in the three dimensions of
      information and training of service providers, management systems in health care
      centers, physical environment and accessibility of hospitals. RESULTS: Most
      hospitals were in a good condition regarding physical environment and access to
      public transportation, but in a poor condition for special healthcare programs
      for the elderly, teaching principles of geriatrics and gerontology, interaction
      of medical staff, physicians and nurses with senior patients and systems of
      priority for them. CONCLUSION: Due to the growing elderly population, it is
      necessary for health policymakers, especially in developing countries, to
      consider seriously the issue of elderly healthcare and their need for special
      outpatient and inpatient services.

PMID- 26000246
TI  - Pinch strengths in healthy Iranian children and young adult population.
AB  - BACKGROUND: Data on the physical strength capabilities are essential for
      designing safe and usable products and are useful in a wide range of clinical
      settings especially during treatment of disease affecting the function of the
      hand. The purpose of this study was to determine peak lateral pinch strength, key
      pinch strength, tip-to-tip pinch strength and three-jaw pinch strength exertions
      in a healthy Iranian children and young adult population. METHODS: The study was
      conducted among 511 participants (242 males and 269 females) aged 7-30 years.
      Measurements were carried out with both dominant and non-dominant hands in
      standard sitting posture using a B&L pinch gauge. Two repetitions of each
      strength measurement were recorded for each condition and the average value of
      the two trials was used in the subsequent analysis. RESULTS: The results showed
      significant differences in the pinch strength data in terms of the age, gender
      and hand dominance. The lateral pinch strength, key pinch strength, tip-to-tip
      pinch strength and three-jaw pinch strength exertions by females were 68.4%,
      68.8%, 78.8% and 81.8% of those exerted by males, respectively. Strength
      exertions with the non-dominant hand were 6.4%, 5.2%, 6.6% and 5.1% lower than
      strength exertions of the dominant hand for the lateral pinch strength, key pinch
      strength, tip-to-tip pinch strength and three-jaw pinch strength exertions,
      respectively. CONCLUSION: These findings can be used to fill the gaps in strength
      data for Iranian population.

PMID- 26000247
TI  - Belief-based Tobacco Smoking Scale: Evaluating the Psychometric Properties of the
      Theory of Planned Behavior's Constructs.
AB  - BACKGROUND: At present, there are no comprehensive validated instruments for
      measuring adolescents' beliefs regarding tobacco smoking in the Iranian society.
      This study aimed to evaluate the validity, reliability and feasibility of the
      belief-based tobacco smoking scale using the Theory of Planned Behavior's (TPB)
      constructs as a theoretical framework. METHODS: This cross-sectional validation
      study was carried out on 410 male adolescents of Hamadan, west of Iran, recruited
      through multi-stage random sampling method. Reliability was assessed by internal
      consistency and Intraclass Correlation Coefficient (ICC). In addition,
      Confirmatory Factor Analyses (CFA) and Exploratory Factor Analyses (EFA) were
      performed to test construct validity. Content validity was examined using Content
      Validity Index (CVI) and Content Validity Ratio (CVR). RESULTS: RESULTS obtained
      from factor analysis showed that the data was fit to the model (X(2)=391.43,
      P<0.001) and TPB consisted of 22 items measuring seven components which
      explaining 69.7% of the common variance. The mean scores for the CVI and CVR were
      0.89 and 0.80; respectively. Additional anal-yses indicated acceptable results
      for internal consistency reliability values ranging from 0.55 to 0.92.
      CONCLUSION: The belief-based tobacco smoking questionnaire is a reliable and
      valid instrument and now is acceptable and suitable and can be used in future
      studies.

PMID- 26000248
TI  - Iranian dietary patterns and risk of colorectal cancer.
AB  - BACKGROUND: Role of diet on colorectal cancer (CRC) has been considered in terms
      of single foods and nutrients, but less frequently in terms of dietary patterns
      in Iran. The objective of this study was to determine the association between
      Iranian dietary patterns and CRC. METHODS: This case-control study was conducted
      in four hospitals in Tabriz City of Iran including 414 participants aged 35-75
      years:207 cases with CRC confirmed by pathology and colonoscopy findings were
      selected and 207 controls free of neoplastic conditions and diet-related chronic
      diseases (from the same hospital at the same period for the cases). Dietary data
      were assessed using a 123-item semi-quantitative food frequency questionnaire.
      Two dietary patterns were found by using of Principal Component Analysis (PCA)
      method;"Healthy pattern"and "Iranian pattern". Multivariate logistic regression
      analysis was used to estimate adjusted odds ratios (OR) for relationship between
      dietary patterns and colorectal cancer. RESULTS: After adjusting for confounding
      factors, the Iranian dietary pattern was significantly associated with an
      increased odds of colorectal cancer (OR= 1.46; 95% Confidenec Interval (CI)=1.05
      2.19) while a reduced odds of colorectal cancer was observed with the Healthy
      dietary pattern (OR=0.18; 95% CI= 0.091-0.47). CONCLUSION: Iranian dietary
      pattern (IDP) seems to increase the odds of colorectal cancer and protective
      effect of Healthy dietary pattern.

PMID- 26000249
TI  - SBRT: An Opportunity to Improve Quality of Life for Oligometastatic Prostate
      Cancer.
AB  - OBJECTIVE: Oligometastatic prostate cancer is a limited metastatic disease state
      in which potential long-term control is still possible with the use of targeted
      therapies such as surgery or stereotactic body radiation therapy (SBRT). SBRT may
      as well potentially prolong the time before the initiation of androgen
      deprivation therapy (ADT) and docetaxel chemotherapy for oligometastatic prostate
      cancer. The goal of this study is to outline prognostic factors associated with
      improved outcome with SBRT for metastatic prostate cancer and to quantify the
      effect of prior systemic treatments such as ADT and docetaxel on survival after
      SBRT. METHODS: Twenty-four prostate cancer patients were treated with SBRT at the
      Philadelphia CyberKnife Center between August 2007 and April 2014. Retrospective
      data collection and analysis were performed for these patients on this
      Institutional Review Board approved study. Kaplan-Meier methodology was utilized
      to estimate and visually assess overall survival (OS) at the patient level, with
      comparisons accomplished using the log-rank test. Unadjusted hazard ratios were
      estimated using Cox proportional hazards regression modeling. RESULTS: An
      improved median survival was noted for patients with oligometastatic disease
      defined as <=4 lesions with median survival of >3 years compared with 11 months
      for polymetastases (p = 0.02). The use of docetaxel at some time in follow-up
      either before or after SBRT was associated with decreased survival with median
      survival of 9 months vs. >3 years (p = 0.01). CONCLUSION: Prognosis was better
      for men with recurrent prostate cancer treated with SBRT if they had <=4
      metastases (oligometastases) or if docetaxel was not necessary for salvage
      treatment. The prolonged median OS for men with oligometastases in this
      population of heavily pretreated prostate cancer patients following SBRT may
      allow for improved quality of life because of a delay of more toxic salvage
      therapies.

PMID- 26000250
TI  - Hypoxia-independent drivers of melanoma angiogenesis.
AB  - Tumor angiogenesis is a process which is traditionally regarded as the tumor's
      response to low nutrient supply occurring under hypoxic conditions. However,
      hypoxia is not a pre-requisite for angiogenesis. The fact that even single tumor
      cells or small tumor cell aggregates are capable of attracting blood vessels
      reveals the early metastatic capability of tumor cells. This review sheds light
      on the hypoxia-independent mechanisms of tumor angiogenesis in melanoma. 

PMID- 26000253
TI  - Isotopic evidence for dietary niche overlap between barking deer and four-horned
      antelope in Nepal.
AB  - BACKGROUND: Morphologically similar sympatric species may have a high degree of
      niche overlap. Barking deer Muntiacus vaginalis and four-horned antelope
      Tetracerus quadricornis are solitary ungulates of the Indian sub-continent.
      Limited information is available regarding their trophic ecology, particularly of
      the endemic four-horned antelope. We present stable carbon (delta(13)C), nitrogen
      (delta(15)N), and sulphur (delta(34)S) isotopic values, and nitrogen content (%N)
      of faeces from barking deer and four-horned antelope living in lowland Nepal to
      assess trophic niche differentiation of these herbivores along the browser-grazer
      continuum. We also describe trophic differences between those two species in
      ecological niches and seasonal effects on their diets. RESULTS: We found that the
      barking deer and four-horned antelope consumed C3 plant sources exclusively. The
      niche partitioning in their diet was reflected by delta(34)S values. Some
      seasonal effects observed were: delta(13)C and delta(15)N were significantly
      lower in the dry season diet of four-horned antelope than that of barking deer,
      while delta(34)S values were significantly higher in the winter diet; monsoon
      diet was similar for both species. Faecal N levels for barking deer and four
      horned antelope were similar throughout all the seasons, indicating that both
      species adapted their feeding behaviour so as to maximize protein intake, in
      accordance with season and environment. CONCLUSIONS: Barking deer and four-horned
      antelope both are browsers; their dietary sources overlapped during monsoon but
      differed during the dry season. Conservation actions focused on resource
      management during the dry season to reduce food scarcity and competition over
      limited resources is likely to be the most effective.

PMID- 26000251
TI  - Mouthguards: does the indigenous microbiome play a role in maintaining oral
      health?
AB  - The existence of symbiotic relationships between bacteria and their hosts in
      various ecosystems have long been known to science. The human body also hosts
      vast numbers of bacteria in several habitats. Emerging evidence from the gastro
      intestinal tract, genito-urinary tract and respiratory indicates that there are
      several health benefits to hosting a complex and diverse microbial community.
      Bacteria colonize the oral cavity within a few minutes after birth and form
      stable communities. Our knowledge of the oral microbiome has expanded
      exponentially with development of novel exploratory methods that allow us to
      examine diversity, structure, function, and topography without the need to
      cultivate the individual components of the biofilm. The purpose of this
      perspective, therefore, is to examine the strength of current evidence supporting
      a role for the oral microbiome in maintaining oral health. While several lines of
      evidence are emerging to suggest that indigenous oral microbiota may have a role
      in immune education and preventing pathogen expansion, much more work is needed
      to definitively establish whether oral bacteria do indeed contribute to
      sustaining oral health, and if so, the mechanisms underlying this role. 

PMID- 26000252
TI  - Occurrence of bla CTX-M-1, qnrB1 and virulence genes in avian ESBL-producing
      Escherichia coli isolates from Tunisia.
AB  - Avian ESBL-producing Escherichia coli isolates have been increasingly reported
      worldwide. Animal to human dissemination, via food chain or direct contact, of
      these resistant bacteria has been reported. In Tunisia, little is known about
      avian ESBL- producing E. coli and further studies are needed. Seventeen ESBL
      producing Escherichia coli isolates from poultry feces from two farms (Farm 1 and
      farm 2) in the North of Tunisia have been used in this study. Eleven of these
      isolates (from farm 1) have the same resistance profile to nalidixic acid,
      sulfonamides, streptomycin, tetracycline, and norfloxacine (intermediately
      resistant). Out of the six isolates recovered from farm 2, only one was co
      resistant to tetracycline. All isolates, except one, harbored bla CTX-M-1 gene,
      and one strain co-harbored the bla TEM-1 gene. The genes tetA and tetB were
      carried, respectively, by 11 and 1 amongst the 12 tetracycline-resistant
      isolates. Sulfonamides resistance was encoded by sul1, sul2, and sul3 genes in 3,
      17, and 5 isolates, respectively. The qnrB1 was detected in nine strains, one of
      which co-harbored qnrS1 gene. The search for the class 1 and 2 integrons by PCR
      showed that in farm 1, class 1 and 2 integrons were found in one and ten
      isolates, respectively. In farm 2, class 1 integron was found in only one
      isolate, class 2 was not detected. Only one gene cassette arrangement was
      demonstrated in the variable regions (VR) of the 10 int2-positive isolates: dfrA1
      sat2-aadA1. The size of the VR of the class 1 integron was approximately 250 bp
      in one int1-positive isolate, whereas in the second isolate, no amplification was
      observed. All isolates of farm 1 belong to the phylogroup A (sub-group A0).
      However, different types of phylogroups in farm 2 were detected. Each of the
      phylogroups A1, B22, B23 was detected in one strain, while the D2 phylogroup was
      found in 3 isolates. The virulence genes iutA, fimH, and traT were detected in 3,
      7, and 3 isolates, respectively. Two types of gene combination were detected:
      iutA+fimH+traT in 3 isolates and iutA+fimH in one isolate. The isolates recovered
      in farm 1 showed the same profile of PFGE macro-restriction, while isolates of
      farm 2 presented unrelated PFGE patterns. We conclude that these avian ESBL
      producing E. coli isolates show homo- and heterogenic genetic background and that
      plasmids harboring ESBL genes could be involved in the dissemination of this
      resistance phenotype. 

PMID- 26000254
TI  - Study of NGEP expression in androgen sensitive prostate cancer cells: A potential
      target for immunotherapy.
AB  - BACKGROUND: Prostate cancer is one of the leading causes of cancer deaths among
      men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed
      only in normal prostate and prostate cancer tissue. Because of its selective
      expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic
      target. To target the NGEP in prostate cancer, it is essential to investigate its
      expression in prostate cancer cells. METHODS: In the present study, we
      investigated NGEP expression in LNCaP and DU145 cells by real time and RT-PCR,
      flow cytometric and immunocytochemical analyses. RESULTS: Real time and RT-PCR
      analyses of NGEP expression showed that NGEP was expressed in the LNCaP cells but
      not in DU145 cells. The detection of NGEP protein by flow cytometric and
      immunocytochemistry analyses indicated that NGEP protein was weakly expressed
      only in LNCaP cell membrane. CONCLUSION: Our results demonstrate that LNCaP cell
      line is more suitable than DU145 for NGEP expression studies; however, its low
      level expression is a limiting issue. NGEP expression may be increased by
      androgen supplementation of LNCaP cell culture medium.

PMID- 26000255
TI  - Different patterns of association between education and wealth with non-fatal
      myocardial infarction in Tehran, Iran: A population-based case-control study.
AB  - BACKGROUND: Myocardial Infarction (MI) is a main cause of death and disability
      worldwide, which involves a number of genetic, physiopathologic and socio
      economic determinants. The aim of this study was to assess the patterns of
      association between education, wealth and some other risk factors with non-fatal
      MI in Tehran population. METHODS: Data derived from a second round of large cross
      sectional study, Urban HEART-2, conducted in Tehran in 2011. Out of 118542
      participants, all 249 self-reported incident cases of nonfatal MI were selected
      as the case group. A number of 996, matched on age and sex, were selected as
      controls. Principle component analysis (PCA) was used to calculate wealth index
      and logistic regression model to assess relations between the study variables.
      RESULTS: Mean (SD) age of participants was 60.25 (12.26) years. A total of 870
      (69.9%) of the study subjects were men. Education, wealth status, family
      violence, hypertension and diabetes were observed as independent predictors of
      non-fatal MI. Overall, as the level of education increased, the odds of non-fatal
      MI decreased (p<0.001). We observed an almost J-shaped association between wealth
      status and non-fatal MI. No significant associations were found between marital
      status, BMI and current smoking with non-fatal MI (p<0.05). CONCLUSION: We found
      different patterns of association between education and wealth with nonfatal MI
      among Tehran adults. Lower risk of non-fatal MI is linked to high educated groups
      whereas economically moderate group has the lowest risk of non-fatal MI
      occurrence.

PMID- 26000256
TI  - Assessing mental health literacy: What medical sciences students' know about
      depression.
AB  - BACKGROUND: Mental health literacy is an individual's knowledge and belief about
      mental disorders which aid their recognition, management and prevention. The aim
      of this study was to investigate mental health literacy among students of Tehran
      University of Medical Sciences. METHODS: In this cross-sectional study, data were
      collected by the anonymous self-administered questionnaires and finally 324
      students participated in the study. Random cluster sampling was used. Questions
      were in different areas of the mental health literacy for depression include
      recognition of disorder, intended actions to seek help and perceived barriers,
      beliefs about interventions, prevention, stigmatization and impact of media. T
      test was used for statistical analysis. RESULTS: The mean (+/-SD) age was 23.5+/
      2.8. The participants were 188 (58.1%) females and 136 (41.9%) males. In response
      to the recognition of the disorder 115 (35.6%) students mentioned the correct
      answer. In help-seeking area, 208 (64.3%) gave positive answer. The majority of
      affected students sought for help from their friends and parents. Stigma was the
      greatest barrier for seeking help. Television and Internet were the most common
      sources of information related to mental health. CONCLUSION: Generally students'
      mental health literacy on depression was low in some areas. Appropriate
      educational programs specifically for reducing mental disorders stigma seems
      necessary. Organizing networks of co-helper students for mental health could be
      considered.

PMID- 26000257
TI  - Effects of e-learning, lectures, and role playing on nursing students' knowledge
      acquisition, retention and satisfaction.
AB  - BACKGROUND: Nursing education can maintain its dynamic quality when it moves
      toward innovation and modern methods of teaching and learning. Therefore,
      teachers are required to employ up to date methods in their teaching plans. This
      study evaluated the effects of e-learning, lectures, and role playing on nursing
      students' learning, retention, and satisfaction. METHODS: Sixty nursing students
      were selected as an experiment and control groups during two consecutive
      semesters. The educational content was presented as e-learning and role playing
      during one semester (experiment group) and as lectures in the next semester
      (control group). A questionnaire containing three parts was used to assess
      demographics, learning and satisfaction statuses. The questionnaire also included
      a final openended question to evaluate the students' ideas about the whole
      course. RESULTS: The mean scores of posttest were 16.13 +/- 1.37 using role
      playing, 15.50 +/- 1.44 using e-learning and 16.45 +/- 1.23 using lectures. The
      differences between the mean scores of posttest and pretest were 12.84 +/- 1.43,
      12.56 +/- 1.57, and 13.73 +/- 1.53 in the mentioned methods, respectively.
      Lectures resulted in significantly better learning compared to role playing and e
      learning. In contrast, retention rates were significantly lower using lectures
      than using role playing and e-learning. Students' satisfaction from e-learning
      was significantly lower than lecturing and role playing. CONCLUSION: Due to the
      lower rates of retention following lectures, the teachers are recommended to use
      student- centered approaches in their lectures. Since students' satisfaction with
      e-learning was lower than the other methods, further studies are suggested to
      explore the problems of e-learning in Iran.

PMID- 26000258
TI  - Evaluating the prior knowledge of toxoplasmosis among students of Ferdowsi
      University of Mashhad.

PMID- 26000260
TI  - Does leadership effectiveness correlates with leadership styles in healthcare
      executives of Iran University of Medical Sciences.
AB  - BACKGROUND: Effective leadership is essential to passing through obstacles facing
      the health field.The current health care system in Iran has major problems and
      gaps in the field of effective leadership. The aim of this study was to evaluate
      hospital managers' leadership style through selfassessment and to determine the
      correlation between leadership styles with healthcare executives' leadership
      readiness and leadership effectiveness. METHODS: In this cross-sectional study a
      self-administered questionnaire completed by all internal healthcare executives
      of all teaching and non-teaching hospitals affiliated to Iran University of
      Medical Sciences. Questionnaire was composed to determine demographic
      information, leadership style questions, leadership effectiveness and leadership
      readiness. Descriptive statistics and Pearson correlation coefficient were used
      for data analysis. RESULTS: According to the findings, the dominant style of
      healthcare executives was transformational leadership style (with a score of
      4.34). The leadership effectiveness was estimated at about 4.36 that shows the
      appropriate level of leadership effectiveness. There was a significant
      correlation (correlation coefficient of 0.244) between leadership readiness and
      transformational leadership style (p<0.05). Also, there was a significant
      correlation between leadership effectiveness with transformational (0.051) and
      transactional (0.216) styles. CONCLUSION: There was a correlation between
      leadership readiness and leadership effectiveness with leadership styles.
      Application of this research will be crucial to universities and healthcare
      executives. This study suggests that strengthening the scientific basis is
      essential for leadership readiness and leadership effectiveness in healthcare
      system.

PMID- 26000259
TI  - Sequence-based genotyping of hepatitis B virus in general population.
AB  - BACKGROUND: Hepatitis B Virus (HBV) causes acute and chronic liver disease
      worldwide. HBV has eight genotypes (A to H) which is the reflection of its genome
      with their characteristic geographical distribution. Each genotype could have
      different pathogenic and therapeutic characteristics. There have been few records
      on HBV genotyping in general population from our region. This study aimed to
      determine hepatitis B genotypes using sequencing in the general population of
      Shahrekord, a Southwestern region of Iran. METHODS: A total of 3000 serum samples
      (cluster sampling method) were enrolled from general population tested for HBsAg
      using ELISA. Using appropriate extraction kit, HBV DNA was extracted from HBsAg
      positive samples and each was subjected to nested PCR for detection of HBV DNA.
      Finally, using sequencing, the samples were used for HBV genotyping. Data were
      analyzed by SPSS 19 using descriptive statistics, chi square, and Fisher's exact
      test. P-value < 0.05 was considered as the level of significance. RESULTS: Out of
      3000 serum samples, 40 (1.3%) were positive for HBsAg. HBV DNA was detected in 10
      out of 40 (25%) of the samples studied. Genotype D was the predominant HBV type
      found in all of these 10 HBV positive samples. CONCLUSION: Genotype D is probably
      the predominant HBV type in our region.

PMID- 26000261
TI  - Vitamin B12 supplementation in end stage renal diseases: a systematic review.
AB  - BACKGROUND: Hyperhomocysteinemia is a risk factor for cardiovascular disease
      particularly in patients with end stage renal disease (ESRD). Vitamin B12
      supplementation on its own still remains as a controversial issue for clinicians
      in decreasing the level of homcysteine in this group of patients. METHODS: Using
      all randomized controlled trials (RCTs), clinical trials and pre-post-trial
      studies found during January 1999 to March 2014, we conducted a systematic review
      which assessed the effects of vitamin B12 in decreasing homocysteine levels in
      patients with ESRD. RESULTS: The findings of this study revealed that, overall,
      the greatest effect of B12 supplementation on decreasing homocysteine levels in
      patients with ESRDs occurred when it was combined with folate supplementation. It
      was also demonstrated that injection treatments might be more beneficial than
      oral intake treatments. CONCLUSION: More rigorous studies are needed to draw a
      firm conclusion about B12 therapy and the level of homocyteine in patients with
      ESRD.

PMID- 26000262
TI  - Stem cell-based approach for the treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative brain
      disorder which is around 1.5 times more common in men than in women. Currently,
      drug medications, surgery, and lifestyle changes are common approaches to PD,
      while all of them focused on reducing the symptoms. Therefore, regenerative
      medicine based on stem cell (SC) therapies has raised a promising hope. Various
      types of SCs have been used in basic and experimental studies relevant to PD,
      including embryonic pluripotential stem cells, mesenchymal (MSCs) and induced
      pluripotent SCs (iPSCs). MSCs have several advantages over other counterparts.
      They are easily accessible which can be obtained from various tissues such as
      bone marrow, adipose tissue, peripheral blood, etc. with avoiding ethical
      problems. Therefore, MSCs is attractive clinically because there are no related
      ethical and immunological concerns . Further studies are needed to answer some
      crucial questions about the different issues in SC therapy. Accordingly, SC-based
      therapy for PD also needed more complementary evaluation in both basic and
      clinical study areas. 

PMID- 26000264
TI  - Evaluation of Gestational Diabetes Mellitus Risk in South Indian Women Based on
      MTHFR (C677T) and FVL (G1691A) Mutations.
AB  - We aimed to scrutinize the extent to which single amino acid substitutions in the
      MTHFR and factor V Leiden (FVL) genes affect the risk of gestational diabetes
      mellitus (GDM) in pregnant women of South Indian descendant. This case-control
      study was implemented once the ethical approval has been obtained. Overall, 237
      women were recruited in this study: 137 had been diagnosed with GDM and the
      remaining 100 women were used as normal controls or non-GDM. The diagnosis of GDM
      was confirmed with biochemical analysis, i.e., GCT and oral glucose tolerance
      tests. Five milliliters of peripheral blood was collected and used for
      biochemical and molecular analyses. DNA was isolated, and genotyping for MTHFR
      (C677T) and FVL (G1691A) mutations was performed using PCR-RFLP. FVL (G1691A)
      locus was not polymorphic in the investigated sample. There was no significant
      difference in the allele and genotype frequencies of C677T polymorphism between
      GDM and non-GDM women (p = 0.8892). 

PMID- 26000263
TI  - Immunotherapy for bladder cancer.
AB  - It is nearly 40 years since Bacillus Calmette-Guerin (BCG) was first used as an
      immunotherapy to treat superficial bladder cancer. Despite its limitations, to
      date it has not been surpassed by any other treatment. As a better understanding
      of its mechanism of action and the clinical response to it have evolved, some of
      the questions around optimal dosing and treatment protocols have been answered.
      However, its potential for toxicity and failure to produce the desired clinical
      effect in a significant cohort of patients presents an ongoing challenge to
      clinicians and researchers alike. This review summarizes the evidence behind the
      established mechanism of action of BCG in bladder cancer, highlighting the
      extensive array of immune molecules that have been implicated in its action. The
      clinical aspects of BCG are discussed, including its role in reducing recurrence
      and progression, the optimal treatment regime, toxicity and, in light of new
      evidence, whether or not there is a superior BCG strain. The problems of toxicity
      and non-responders to BCG have led to development of new techniques aimed at
      addressing these pitfalls. The progress made in the laboratory has led to the
      identification of novel targets for the development of new immunotherapies. This
      includes the potential augmentation of BCG with various immune factors through to
      techniques avoiding the use of BCG altogether; for example, using interferon
      activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The
      potential role of gene, virus, or photodynamic therapy as an alternative to BCG
      is also reviewed. Recent interest in the immune check point system has led to the
      development of monoclonal antibodies against proteins involved in this pathway.
      Early findings suggest benefit in metastatic disease, although the role in
      superficial bladder cancer remains unclear. 

PMID- 26000265
TI  - Clinical risk factors for central line-associated venous thrombosis in children.
AB  - BACKGROUND: Identifying risk factors related to central venous line (CVL)
      placement could potentially minimize central line-associated venous thrombosis
      (CLAVT). We sought to identify the clinical factors associated with CLAVT in
      children. METHODS: Over a 3-year period, 3733 CVLs were placed at a tertiary-care
      children's hospital. Data were extracted from the electronic medical records of
      patients with clinical signs and symptoms of venous thromboembolism, diagnosed
      using Doppler ultrasonography and/or echocardiography. Statistical analyses
      examined differences in CLAVT occurrence between groups based on patient and CVL
      characteristics (type, brand, placement site, and hospital unit). RESULTS:
      Femoral CVL placement was associated with greater risk for developing CLAVT (OR
      11.1, 95% CI 3.9-31.6, p < 0.0001). CVLs placed in the NICU were also associated
      with increased CLAVT occurrence (OR 5.3, 95% CI 2.1-13.2, p = 0.0003). CVL brand
      was also significantly associated with risk of CLAVT events. CONCLUSION:
      Retrospective analyses identified femoral CVL placement and catheter type as
      independent risk factors for CLAVT, suggesting increased risks due to mechanical
      reasons. Placement of CVLs in the NICU also led to an increased risk of CLAVT,
      suggesting that small infants are at increased risk of thrombotic events.
      Alternative strategies for CVL placement, thromboprophylaxis, and earlier
      diagnosis may be important for reducing CLAVT events.

PMID- 26000267
TI  - Renal artery stenosis precipitates hyponatremic hypertensive syndrome and
      posterior reversible leukoencephalopathy.
AB  - BACKGROUND: Hyponatremic hypertensive syndrome (HHS) is an uncommon disorder
      usually encountered in the adult population with unilateral renal artery stenosis
      and is under-recognized in the pediatric population. CASE DIAGNOSIS/TREATMENT: A
      19-month-old male presented with new-onset status epilepticus associated with
      neurological sequelae, and hypertension to a high of 248/150 mmHg. Lab work
      revealed significant hyponatremia, elevated peripheral renin activity, and
      increase in aldosterone and ADH levels. A diagnosis of HHS was made. Initial
      analysis revealed a high-grade proximal renal artery stenosis by magnetic
      resonance imaging (MRI) and angiogram. Electroencephalogram and an MRI of the
      brain demonstrated characteristic abnormalities of the left temporal-parietal
      regions consistent with posterior reversible leukoencephalopathy syndrome (PRES).
      The patient responded to right renal artery balloon dilation and stent placement.
      Since intervention and close blood pressure control with Amlodipine, the patient
      has been free of seizures and is neurologically intact. CONCLUSION: We report a
      case of malignant hypertension in a 19-month-old male secondary to renal artery
      stenosis with associated HHS and PRES. Prognosis of PRES in children with renal
      disease is excellent. Prompt intervention may offer near complete resolution of
      physiologic and symptomatic effects of HHS and PRES due to high-grade renal
      artery stenosis. This report was written with parental consent for de-identified
      case presentation and radiographs for the educational benefit of other medical
      professionals.

PMID- 26000266
TI  - Strategies for the identification and tracking of cronobacter species: an
      opportunistic pathogen of concern to neonatal health.
AB  - Cronobacter species are emerging opportunistic food-borne pathogens, which
      consists of seven species, including C. sakazakii, C. malonaticus, C. muytjensii,
      C. turicensis, C. dublinensis, C. universalis, and C. condimenti. The organism
      can cause severe clinical infections, including necrotizing enterocolitis,
      septicemia, and meningitis, predominately among neonates <4 weeks of age.
      Cronobacter species can be isolated from various foods and their surrounding
      environments; however, powdered infant formula (PIF) is the most frequently
      implicated food source linked with Cronobacter infection. This review aims to
      provide a summary of laboratory-based strategies that can be used to identify and
      trace Cronobacter species. The identification of Cronobacter species using
      conventional culture method and immuno-based detection protocols were first
      presented. The molecular detection and identification at genus-, and species
      level along with molecular-based serogroup approaches are also described,
      followed by the molecular sub-typing methods, in particular pulsed-field gel
      electrophoresis and multi-locus sequence typing. Next generation sequence
      approaches, including whole genome sequencing, DNA microarray, and high
      throughput whole-transcriptome sequencing, are also highlighted. Appropriate
      application of these strategies would contribute to reduce the risk of
      Cronobacter contamination in PIF and production environments, thereby improving
      food safety and protecting public health. 

PMID- 26000268
TI  - Picky eating in children.

PMID- 26000270
TI  - The Relationship between Habitual Breakfast Consumption Frequency and Academic
      Performance in British Adolescents.
AB  - Breakfast has been shown to be beneficial for cognitive and academic performance
      in school children. However, there is a paucity of studies which examine the
      relationship between breakfast consumption and academic performance and a
      complete absence of studies in UK school children. The aim of this study,
      therefore, was to examine the association between habitual breakfast consumption
      frequency and Cognitive Abilities Test (CAT) performance, a reasoning test
      routinely used in UK schools. Adolescents aged 11-13 years (n = 292; males:
      53.8%) completed a questionnaire to report usual weekly breakfast intake
      frequency. Breakfast was subjectively defined by the participants. Habitual
      weekly breakfast consumption frequency was categorized as rare (0-2 days),
      occasional (3-4 days), or frequent (5-7 days). Participants' CAT performance was
      used as a proxy measure of academic performance. The CAT has three components:
      verbal, non-verbal, and quantitative reasoning. Normative standard age scores
      (SAS) for verbal, non-verbal, quantitative reasoning, and overall mean SAS were
      obtained from school records and hierarchical linear regression models were
      applied, adjusting for the confounders: gender, ethnicity, socio-economic status,
      English as an Additional Language, and body mass index. Habitual breakfast
      consumption frequency did not significantly predict any CAT SAS in all models
      (crude and adjusted). However, methodological considerations which could account
      for this disagreement with previous research, were identified. These included the
      isolation of school-day breakfast consumption, use of a standard definition of
      breakfast, and measurement of actual academic performance. The findings of the
      current study suggest more comprehensive ways in which future studies might
      investigate the relationship between habitual breakfast consumption and academic
      performance. 

PMID- 26000269
TI  - The cerebellum and psychiatric disorders.
AB  - The cerebellum has been considered for a long time to play a role solely in motor
      coordination. However, studies over the past two decades have shown that the
      cerebellum also plays a key role in many motor, cognitive, and emotional
      processes. In addition, studies have also shown that the cerebellum is implicated
      in many psychiatric disorders including attention deficit hyperactivity disorder,
      autism spectrum disorders, schizophrenia, bipolar disorder, major depressive
      disorder, and anxiety disorders. In this review, we discuss existing studies
      reporting cerebellar dysfunction in various psychiatric disorders. We will also
      discuss future directions for studies linking the cerebellum to psychiatric
      disorders. 

PMID- 26000271
TI  - Biomarker identification and effect estimation on schizophrenia - a high
      dimensional data analysis.
AB  - Biomarkers have been examined in schizophrenia research for decades. Medical
      morbidity and mortality rates, as well as personal and societal costs, are
      associated with schizophrenia patients. The identification of biomarkers and
      alleles, which often have a small effect individually, may help to develop new
      diagnostic tests for early identification and treatment. Currently, there is not
      a commonly accepted statistical approach to identify predictive biomarkers from
      high dimensional data. We used space decomposition-gradient-regression (DGR)
      method to select biomarkers, which are associated with the risk of schizophrenia.
      Then, we used the gradient scores, generated from the selected biomarkers, as the
      prediction factor in regression to estimate their effects. We also used an
      alternative approach, classification and regression tree, to compare the
      biomarker selected by DGR and found about 70% of the selected biomarkers were the
      same. However, the advantage of DGR is that it can evaluate individual effects
      for each biomarker from their combined effect. In DGR analysis of serum specimens
      of US military service members with a diagnosis of schizophrenia from 1992 to
      2005 and their controls, Alpha-1-Antitrypsin (AAT), Interleukin-6 receptor (IL
      6r) and connective tissue growth factor were selected to identify schizophrenia
      for males; and AAT, Apolipoprotein B and Sortilin were selected for females. If
      these findings from military subjects are replicated by other studies, they
      suggest the possibility of a novel biomarker panel as an adjunct to earlier
      diagnosis and initiation of treatment. 

PMID- 26000272
TI  - Grand challenges in digital health.

PMID- 26000273
TI  - BRIC's Growing Share of Global Health Spending and Their Diverging Pathways.

PMID- 26000274
TI  - High Modulus Biodegradable Polyurethanes for Vascular Stents: Evaluation of
      Accelerated in vitro Degradation and Cell Viability of Degradation Products.
AB  - We have recently reported the mechanical properties and hydrolytic degradation
      behavior of a series of NovoSorbTM biodegradable polyurethanes (PUs) prepared by
      varying the hard segment (HS) weight percentage from 60 to 100. In this study,
      the in vitro degradation behavior of these PUs with and without extracellular
      matrix (ECM) coating was investigated under accelerated hydrolytic degradation
      (phosphate buffer saline; PBS/70 degrees C) conditions. The mass loss at
      different time intervals and the effect of aqueous degradation products on the
      viability and growth of human umbilical vein endothelial cells (HUVEC) were
      examined. The results showed that PUs with HS 80% and below completely
      disintegrated leaving no visual polymer residue at 18 weeks and the degradation
      medium turned acidic due to the accumulation of products from the soft segment
      (SS) degradation. As expected the PU with the lowest HS was the fastest to
      degrade. The accumulated degradation products, when tested undiluted, showed
      viability of about 40% for HUVEC cells. However, the viability was over 80% when
      the solution was diluted to 50% and below. The growth of HUVEC cells is similar
      to but not identical to that observed with tissue culture polystyrene standard
      (TCPS). The results from this in vitro study suggested that the PUs in the series
      degraded primarily due to the SS degradation and the cell viability of the
      accumulated acidic degradation products showed poor viability to HUVEC cells when
      tested undiluted, however particles released to the degradation medium showed
      cell viability over 80%. 

PMID- 26000275
TI  - Pannexin channels mediate the acquisition of myogenic commitment in C2C12 reserve
      cells promoted by P2 receptor activation.
AB  - The acquisition of myoblast commitment to the myogenic linage requires rises in
      intracellular free Ca(2+) concentration ([Ca(2+)]i). Putative cell membrane
      pathways involved in these [Ca(2+)]i increments are P2 receptors (P2Rs) as well
      as connexin (Cx) and/or pannexin (Panx) hemichannels and channels (Cx HChs and
      Panx Chs), respectively, which are known to permeate Ca(2+). Reserve cells (RCs)
      are uncommitted myoblasts obtained from differentiated C2C12 cell cultures, which
      acquire commitment upon replating. Regarding these cells, we found that
      extracellular ATP increases the [Ca(2+)]i via P2Rs. Moreover, ATP increases the
      plasma membrane permeability to small molecules and a non-selective membrane
      current, both of which were inhibited by Cx HCh/Panx1Ch blockers. However, RCs
      exposed to divalent cation-free saline solution, which is known to activate Cx
      HChs (but not Panx Chs), did not enhance membrane permeability, thus ruling out
      the possible involvement of Cx HChs. Moreover, ATP-induced membrane permeability
      was inhibited with blockers of P2Rs that activate Panx Chs. In addition,
      exogenous ATP induced the expression of myogenic commitment and increased MyoD
      levels, which was prevented by the inhibition of P2Rs or knockdown of Panx1 Chs.
      Similarly, increases in MyoD levels induced by ATP released by RCs were inhibited
      by Panx Ch/Cx HCh blockers. Myogenic commitment acquisition thus requires a feed
      forward mechanism mediated by extracellular ATP, P2Rs, and Panx Chs. 

PMID- 26000276
TI  - Cell collectivity regulation within migrating cell cluster during Kupffer's
      vesicle formation in zebrafish.
AB  - Although cell adhesion is thought to fasten cells tightly, cells that adhere to
      each other can migrate directionally. This group behavior, called "collective
      cell migration," is observed during normal development, wound healing, and cancer
      invasion. Loss-of-function of cell adhesion molecules in several model systems of
      collective cell migration results in delay or inhibition of migration of cell
      groups but does not lead to dissociation of the cell groups, suggesting that
      mechanisms of cells staying assembled as a single cell cluster, termed as "cell
      collectivity," remain largely unknown. During the formation of Kupffer's vesicle
      (KV, an organ of laterality in zebrafish), KV progenitors form a cluster and
      migrate together toward the vegetal pole. Importantly, in this model system of
      collective cell migration, knockdown of cell adhesion molecules or signal
      components leads to failure of cell collectivity. In this review, we summarize
      recent findings in cell collectivity regulation during collective migration of KV
      progenitor cells and describe our current understanding of how cell collectivity
      is regulated during collective cell migration. 

PMID- 26000277
TI  - Carpal tunnel syndrome: primary care and occupational factors.
AB  - Carpal tunnel syndrome (CTS) affects about 1% of working-aged people and is the
      commonest cause of hand pain in manual workers. CTS is a clinical diagnosis and
      does not warrant any further investigation in the presence of mild and suggestive
      CTS. Although the recommended non-surgical management is still a matter of
      debate, nocturnal splinting or steroid injection are recommended in most
      countries, with strong to moderate level of evidence for short-term efficacy.
      Patients with an uncertain diagnosis or severe symptoms, should undergo nerve
      conduction studies with referral to a hand specialist. 

PMID- 26000278
TI  - Use of leflunomide in renal transplant recipients with ganciclovir
      resistant/refractory cytomegalovirus infection: a case series from the University
      of Chicago.
AB  - INTRODUCTION: Although antiviral prophylaxis for cytomegalovirus (CMV) is widely
      used, CMV infection remains common in renal transplant recipients with adverse
      consequences. METHODS: We report 5 cases of renal transplant recipients with
      resistant CMV infection who were successfully managed with leflunomide at the
      University of Chicago Medical Center. RESULTS: Five renal transplant recipients
      (2 simultaneous pancreas/kidney transplants, 3 deceased donor kidney transplants)
      were diagnosed with GCV-resistant CMV infection from 2003 to 2011. Of the 4
      patients who had resistance genotype testing, 3 showed a UL97 mutation and 1
      patient had a clinically resistant CMV infection. All patients received CMV
      prophylaxis with valganciclovir for 3 months. The number of days from the date of
      transplant to viremia ranged from 38 to 458 days (median 219). All 5 patients
      received other antiviral agents (e.g. ganciclovir, foscarnet), and in 4 patients,
      viremia was cleared before leflunomide was initiated as consolidation (or
      maintenance) therapy. CONCLUSION: Leflunomide was well tolerated and successful
      in preventing recurrence of viremia in renal transplant recipients with resistant
      CMV infection. The beneficial effect of leflunomide in this setting warrants
      further investigation.

PMID- 26000279
TI  - Early-onset diabetic E1-DN mice develop albuminuria and glomerular injury typical
      of diabetic nephropathy.
AB  - The transgenic E1-DN mice express a kinase-negative epidermal growth factor
      receptor in their pancreatic islets and are diabetic from two weeks of age due to
      impaired postnatal growth of beta-cell mass. Here, we characterize the
      development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous
      mice showed increased albumin excretion rate (AER) at the age of 10 weeks; the
      albuminuria increased over time and correlated with blood glucose. Morphometric
      analysis of PAS-stained histological sections and electron microscopy images
      revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis
      was observed in the most hyperglycaemic mice. The albuminuric homozygous mice
      developed also other structural changes in the glomeruli, including thickening of
      the glomerular basement membrane and widening of podocyte foot processes that are
      typical for diabetic nephropathy. Increased apoptosis of podocytes was identified
      as one mechanism contributing to glomerular injury. In addition, nephrin
      expression was reduced in the podocytes of albuminuric homozygous E1-DN mice.
      Tubular changes included altered epithelial cell morphology and increased
      proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and
      glomerular and tubular injury typical of human diabetic nephropathy and can serve
      as a new model to study the mechanisms leading to the development of diabetic
      nephropathy.

PMID- 26000282
TI  - Artemisia allergy research in China.
AB  - Artemisia is the most important outdoor allergen throughout China. It can cause
      allergic rhinitis, asthma, or both of them. Since it was verified as an
      allergenic pollen in 1960, it was identified two times in the Chinese National
      Pollen Survey (1984, 2009). The first oral immunotherapy double-blinded trial for
      Artemisia pollen asthma research was conducted in China in 1989 and published in
      1990. 40 years since that study, there have been many published research reports
      on Chinese Artemisia allergy. This review summarizes the information regarding
      the discovery of Artemisia as an allergenic pollen, pollen account, epidemiology,
      allergen components, immunological changes in hay fever patients, natural course
      from rhinitis to asthma, diagnosis, and immunotherapies in China. 

PMID- 26000280
TI  - Links between Vitamin D Deficiency and Cardiovascular Diseases.
AB  - The aim of the present paper was to review the most important mechanisms
      explaining the possible association of vitamin D deficiency and cardiovascular
      diseases, focusing on recent experimental and clinical data. Low vitamin D levels
      favor atherosclerosis enabling vascular inflammation, endothelial dysfunction,
      formation of foam cells, and proliferation of smooth muscle cells. The
      antihypertensive properties of vitamin D include suppression of the renin
      angiotensin-aldosterone system, renoprotective effects, direct effects on
      endothelial cells and calcium metabolism, inhibition of growth of vascular smooth
      muscle cells, prevention of secondary hyperparathyroidism, and beneficial effects
      on cardiovascular risk factors. Vitamin D is also involved in glycemic control,
      lipid metabolism, insulin secretion, and sensitivity, explaining the association
      between vitamin D deficiency and metabolic syndrome. Vitamin D deficit was
      associated in some studies with the number of affected coronary arteries,
      postinfarction complications, inflammatory cytokines and cardiac remodeling in
      patients with myocardial infarction, direct electromechanical effects and
      inflammation in atrial fibrillation, and neuroprotective effects in stroke. In
      peripheral arterial disease, vitamin D status was related to the decline of the
      functional performance, severity, atherosclerosis and inflammatory markers,
      arterial stiffness, vascular calcifications, and arterial aging. Vitamin D
      supplementation should further consider additional factors, such as phosphates,
      parathormone, renin, and fibroblast growth factor 23 levels. 

PMID- 26000281
TI  - Interplay of vitamin D, erythropoiesis, and the renin-angiotensin system.
AB  - For many years deficiency of vitamin D was merely identified and assimilated to
      the presence of bone rickets. It is now clear that suboptimal vitamin D status
      may be correlated with several disorders and that the expression of 1-alpha
      hydroxylase in tissues other than the kidney is widespread and of clinical
      relevance. Recently, evidence has been collected to suggest that, beyond the
      traditional involvement in mineral metabolism, vitamin D may interact with other
      kidney hormones such as renin and erythropoietin. This interaction would be
      responsible for some of the systemic and renal effects evoked for the therapy
      with vitamin D. The administration of analogues of vitamin D has been associated
      with an improvement of anaemia and reduction in ESA requirements. Moreover,
      vitamin D deficiency could contribute to an inappropriately activated or
      unsuppressed RAS, as a mechanism for progression of CKD and/or cardiovascular
      disease. Experimental data on the anti-RAS and anti-inflammatory effects
      treatment with active vitamin D analogues suggest a therapeutic option
      particularly in proteinuric CKD patients. This option should be considered for
      those subjects that are intolerant to anti-RAS agents or, as add-on therapy, in
      those already treated with anti-RAS but not reaching the safe threshold level of
      proteinuria. 

PMID- 26000283
TI  - Efficacy of Sublingual Immunotherapy with Dermatophagoides farinae Extract in
      Monosensitized and Polysensitized Patients with Allergic Rhinitis: Clinical
      Observation and Analysis.
AB  - AIM: To investigate differences in the efficacy of sublingual immunotherapy with
      Dermatophagoides farinae drops in monosensitized and polysensitized allergic
      rhinitis patients. METHODS: The patients enrolled in the study were treated for
      more than one year by sublingual immunotherapy (SLIT) using Dermatophagoides
      farinae drops and were divided into a monosensitized group (n = 20) and a
      polysensitized group (n = 30). Total nasal symptom scores of patients before and
      after SLIT were analyzed to evaluate the curative effect. The phylogenetic tree
      of dust mite allergens as well as other allergens that were tested by skin prick
      test was constructed to help the analysis. RESULTS: There was no significant
      difference in the efficacy of SLIT between dust mite monosensitized and
      polysensitized patients. CONCLUSIONS: Both dust mite monosensitized and
      polysensitized patients could be cured by SLIT using Dermatophagoides farinae
      drops. This study provides a reference for the selection of allergens to be used
      in immunotherapy for polysensitized AR patients.

PMID- 26000284
TI  - An improved method for completely uncertain biological network alignment.
AB  - With the continuous development of biological experiment technology, more and
      more data related to uncertain biological networks needs to be analyzed. However,
      most of current alignment methods are designed for the deterministic biological
      network. Only a few can solve the probabilistic network alignment problem.
      However, these approaches only use the part of probabilistic data in the original
      networks allowing only one of the two networks to be probabilistic. To overcome
      the weakness of current approaches, an improved method called completely
      probabilistic biological network comparison alignment (C_PBNA) is proposed in
      this paper. This new method is designed for complete probabilistic biological
      network alignment based on probabilistic biological network alignment (PBNA) in
      order to take full advantage of the uncertain information of biological network.
      The degree of consistency (agreement) indicates that C_PBNA can find the results
      neglected by PBNA algorithm. Furthermore, the GO consistency (GOC) and global
      network alignment score (GNAS) have been selected as evaluation criteria, and all
      of them proved that C_PBNA can obtain more biologically significant results than
      those of PBNA algorithm. 

PMID- 26000285
TI  - Vitamin D Status in Women with Gestational Diabetes Mellitus during Pregnancy and
      Postpartum.
AB  - Of many vitamin D extraskeletal functions, its modulatory role in insulin
      secretion and action is especially relevant for gestational diabetes mellitus
      (GDM). The aims of the present study were to determine midgestational and early
      postpartum vitamin D status in pregnant women with and without GDM and to
      describe the relationship between midgestational and postpartum vitamin D status
      and parallel changes of glucose tolerance. A total of 76 pregnant women (47 GDM
      and 29 healthy controls) were included in the study. Plasma levels of 25(OH)D
      were measured using an enzyme immunoassay. Vitamin D was not significantly
      decreased in GDM compared to controls during pregnancy; however, both groups of
      pregnant women exhibited high prevalence of vitamin D deficiency. Prevalence of
      postpartum 25(OH)D deficiency in post-GDM women remained significantly higher and
      their postpartum 25(OH)D levels were significantly lower compared to non-GDM
      counterparts. Finally, based on the oGTT repeated early postpartum persistent
      glucose abnormality was ascertained in 15% of post-GDM women; however, neither
      midgestational nor postpartum 25(OH)D levels significantly differed between
      subjects with GDM history and persistent postpartum glucose intolerance and those
      with normal glucose tolerance after delivery. 

PMID- 26000286
TI  - Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid
      Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register,
      Reuma.pt.
AB  - OBJECTIVES: To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab
      in rheumatoid arthritis (RA) treatment, according to different response criteria.
      METHODS: We included RA patients registered in the Rheumatic Diseases Portuguese
      Register treated with TNFi or tocilizumab for at least 6 months, between January
      2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months
      according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and
      EULAR response rate, adjusting for measured confounders. RESULTS: Tocilizumab
      treated patients (n = 95) presented higher baseline disease activity and were
      less frequently naive to biologics compared to TNFi users (n = 429). Multivariate
      logistic regression analysis including the propensity score for receiving
      tocilizumab showed that patients treated with tocilizumab were more likely to
      achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6-21.6/3.2
      12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2-6.5/1.3-5.5), or SDAI (OR = 3.6/2.5, 95% CI
      1.5-8.7/1.1-5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4-12.0).
      However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8
      4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8-4.5). CONCLUSIONS:
      Compared with TNFi, tocilizumab was associated with greater likelihood of
      achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean
      remission and EULAR good/moderate response did not differ significantly between
      groups.

PMID- 26000287
TI  - Inhibitory effects of eucalyptus and banaba leaf extracts on nonalcoholic
      steatohepatitis induced by a high-fructose/high-glucose diet in rats.
AB  - Nonalcoholic steatohepatitis (NASH) is a liver disease associated with metabolic
      syndrome. The aim of this work was to examine whether eucalyptus (Eucalyptus
      globulus) leaf extract (ELE) and banaba (Lagerstroemia speciosa L.) leaf extract
      (BLE) inhibited NASH induced by excessive ingestion of fructose in rats. Wistar
      rats were divided into four groups according to four distinct diets: starch diet
      (ST), high-fructose/high-glucose diet (FG), FG diet supplemented with ELE, or FG
      diet supplemented with BLE. All rats were killed after 5 weeks of treatment.
      Serum alanine aminotransferase and total cholesterol levels were significantly
      lower in the BLE group than in the FG group. Liver histopathology, including
      steatosis, lipogranulomas, and perisinusoidal fibrosis, was significantly
      attenuated in the ELE and BLE groups compared with the FG group. Levels of 2
      thiobarbituric acid reactive substances (TBARS), which reflect oxidative injury
      to the liver, were significantly suppressed by ELE and BLE. Western blotting
      analysis indicated that interleukin-6 expression levels were significantly lower
      in the ELE and BLE groups than in the FG group. These results suggest that ELE
      and BLE reduced lipogenesis, oxidative stress, and inflammatory cytokine
      expression and thus inhibited NASH induced by excessive ingestion of fructose in
      rats. 

PMID- 26000288
TI  - Association between Arsenic Exposure and Diabetes: A Meta-Analysis.
AB  - Studies on the association between arsenic exposure and diabetes mellitus (DM)
      yielded inconsistent results. Epidemiologic data on the associations between
      arsenic exposures via inhalation and DM are limited. Therefore, we conducted a
      meta-analysis to evaluate the risk of DM associated with arsenic exposure. We
      searched the related literature through a systematic approach and analyzed the
      data according to the exposure route (inhalation and ingestion). We used random
      effect models to estimate the summary relative risks (RRs) for DM associated with
      arsenic exposure and used I (2) statistics to assess the heterogeneity of
      studies. We identified 38 relevant studies, of which the 32 on the ingestion
      route showed a significant association between arsenic exposure and DM (RR =
      1.57; 95% CI 1.27-1.93). Focusing on the 24 studies in which the diagnosis of DM
      was confirmed using laboratory tests or medical records, we found that the
      summary RR was 1.71 (95% CI 1.32-2.23), very close to the overall estimates. We
      concluded that ingested arsenic is associated with the development of DM, but the
      heterogeneity among the studies may affect the results. 

PMID- 26000289
TI  - Drug resistance in hematologic malignancies: induction mechanisms, genetics, and
      therapeutics.

PMID- 26000290
TI  - Predicting flavin and nicotinamide adenine dinucleotide-binding sites in proteins
      using the fragment transformation method.
AB  - We developed a computational method to identify NAD- and FAD-binding sites in
      proteins. First, we extracted from the Protein Data Bank structures of proteins
      that bind to at least one of these ligands. NAD-/FAD-binding residue templates
      were then constructed by identifying binding residues through the ligand-binding
      database BioLiP. The fragment transformation method was used to identify
      structures within query proteins that resembled the ligand-binding templates. By
      comparing residue types and their relative spatial positions, potential binding
      sites were identified and a ligand-binding potential for each residue was
      calculated. Setting the false positive rate at 5%, our method predicted NAD- and
      FAD-binding sites at true positive rates of 67.1% and 68.4%, respectively. Our
      method provides excellent results for identifying FAD- and NAD-binding sites in
      proteins, and the most important is that the requirement of conservation of
      residue types and local structures in the FAD- and NAD-binding sites can be
      verified. 

PMID- 26000291
TI  - Analysis of anaphylactic shock caused by 17 types of traditional Chinese medicine
      injections used to treat cardiovascular and cerebrovascular diseases.
AB  - Several reports describing anaphylactic shock following treatment of
      cardiovascular and cerebrovascular diseases with Chinese herbal injections were
      described. Our analysis of these reports showed that anaphylactic shock caused by
      traditional Chinese medicine (TCM) injections for the treatment of cardiovascular
      and cerebrovascular diseases is common but also sometimes fatal. Therefore, we
      proposed the following four suggestions for improving the clinical safety of
      delivering Chinese herbal injections and reducing the occurrence of allergic
      shock. First, patients with cardiovascular and cerebrovascular diseases are at
      high risk, so they should only be given TCM injections after a doctor's diagnosis
      and approval. Second, people in allergic groups can suffer anaphylactic shock, so
      vigilance is important in the treatment of all age groups, although even more
      caution should be exercised when treating children or elderly people. In fact,
      TCM injections may not be appropriate for those age groups, so that they should
      be carefully considered before treatment. Third, no significant gender
      differences have been noted in patients with anaphylactic shock, so all patients
      should be carefully monitored, irrespective of gender. Fourth, the timeframe in
      which different drugs cause anaphylactic shock varies; thus, patients should be
      observed as long as possible. 

PMID- 26000292
TI  - Synergistic Activity of Carfilzomib and Panobinostat in Multiple Myeloma Cells
      via Modulation of ROS Generation and ERK1/2.
AB  - Relapse of disease and subsequent resistance to established therapies remain as
      major challenges in the treatment of multiple myeloma (MM). New therapeutic
      options are needed for these extensively pretreated patients. To explore an
      optimized combinational therapy, interactions between the irreversible proteasome
      inhibitor carfilzomib exhibiting a well-tolerated side-effect profile and histone
      deacetylase inhibitor (HDACi) panobinostat (LBH589) were examined in MM cells.
      Coadministration of carfilzomib and LBH589 led to a synergistic inhibition of
      proliferation in MM cells. Further studies showed that the combined treatment
      synergistically increased mitochondrial injury, caspase activation, and apoptosis
      in MM cells. Lethality of the carfilzomib/LBH589 combination was associated with
      the reactive oxygen species (ROS) generation and ERK1/2 inactivation. In
      addition, the free radical scavenger N-acetylcysteine (NAC) could block
      carfilzomib and LBH589-induced oxidative stress and the subsequent apoptosis.
      Together, these findings argue that the strategy of combining carfilzomib and
      LBH589 warrants attention in MM. 

PMID- 26000293
TI  - Vitamin D and inflammatory bowel disease.
AB  - Vitamin D deficiency has been recognized as an environmental risk factor for
      Crohn's disease since the early 80s. Initially, this finding was correlated with
      metabolic bone disease. Low serum 25-hydroxyvitamin D levels have been repeatedly
      reported in inflammatory bowel diseases together with a relationship between
      vitamin D status and disease activity. Subsequently, low serum vitamin D levels
      have been reported in various immune-related diseases pointing to an
      immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to
      interact with different players of the immune homeostasis by controlling cell
      proliferation, antigen receptor signalling, and intestinal barrier function.
      Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of
      defensin-beta2, the latter known to play a crucial role in the pathogenesis of
      Crohn's disease (IBD1 gene), and several genetic variants of the vitamin D
      receptor have been identified as Crohn's disease candidate susceptibility genes.
      From animal models we have learned that deletion of the VDR gene was associated
      with a more severe disease. There is a growing body of evidence concerning the
      therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical
      and experimental models of inflammatory bowel disease far beyond the role of
      calcium homeostasis and bone metabolism. 

PMID- 26000295
TI  - A large-scale structural classification of antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) are potent drug candidates against microbial
      organisms such as bacteria, fungi, parasites, and viruses. AMPs have abundant
      sequences and structures, two fundamental resources for bioinformatics
      researches, but analyses on how they associate with each other are either
      nonexistent or limited to partial classification and data. We thus present A
      Database of Anti-Microbial peptides (ADAM), which contains 7,007 unique sequences
      and 759 structures, to systematically establish comprehensive associations
      between AMP sequences and structures through structural folds and to provide an
      easy access to view their relationships. 30 distinct AMP structural fold clusters
      with more than one structure are detected and about a thousand AMPs are
      associated with at least one structural fold cluster. According to ADAM, AMP
      structural folds are limited-AMPs only cover about 3% of the overall protein fold
      space. 

PMID- 26000294
TI  - Isotypes of Epstein-Barr virus antibodies in rheumatoid arthritis: association
      with rheumatoid factors and citrulline-dependent antibodies.
AB  - In order to study the humoral immune response against Epstein-Barr virus (EBV) in
      patients with rheumatoid arthritis (RA) and to compare it with the two major
      autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with
      systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were
      investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages
      of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV
      nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients
      and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM
      against the early lytic EBV antigen diffuse (EAD) were also found in RA patients
      compared to HCs but were highest in SLE patients. Furthermore, associations
      between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and
      IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs,
      IgG) and between elevated IgA concentrations against EAD and the presence of RFs
      and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of
      all isotypes characteristic of latent EBV infection (whereas SLE patients had
      elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and
      IgA (but not IgG), these were associated with the presence of characteristic RA
      autoantibodies. 

PMID- 26000296
TI  - Influence of preoperative peripheral parenteral nutrition with micronutrients
      after colorectal cancer patients.
AB  - BACKGROUND: The inflammatory reactions are stronger after surgery of malnourished
      preoperative patients. Many studies have shown vitamin and trace element
      deficiencies appear to affect the functioning of immune cells. Enteral nutrition
      is often inadequate for malnourished patients. Therefore, total parenteral
      nutrition (TPN) is considered an effective method for providing preoperative
      nutritional support. TPN needs a central vein catheter, and there are more risks
      associated with TPN. However, peripheral parenteral nutrition (PPN) often does
      not provide enough energy or nutrients. PURPOSE: This study investigated the
      inflammatory response and prognosis for patients receiving a modified form of PPN
      with added fat emulsion infusion, multiple vitamins (MTV), and trace elements
      (TE) to assess the feasibility of preoperative nutritional support. Methods. A
      cross-sectional design was used to compare the influence of PPN with or without
      adding MTV and TE on malnourished abdominal surgery patients. RESULTS: Both
      preoperative groups received equal calories and protein, but due to the lack of
      micronutrients, patients in preoperative Group B exhibited higher inflammation,
      lower serum albumin levels, and higher anastomotic leak rates and also required
      prolonged hospital stays. CONCLUSION: Malnourished patients who receive
      micronutrient supplementation preoperatively have lower postoperative
      inflammatory responses and better prognoses. PPN with added fat emulsion, MTV,
      and TE provides valid and effective preoperative nutritional support.

PMID- 26000297
TI  - Changes of the eSheath Outer Dimensions Used for Transfemoral Transcatheter
      Aortic Valve Replacement.
AB  - Innovative catheter systems with lower-profile sheaths and a dynamic expansion
      mechanism (DEM) were recently introduced for transcatheter aortic valve
      replacement (TAVR). However, the labeling of 14 F and 16 F eSheaths denote the
      inner nominal diameter. Exact changes of the clinically relevant outer diameters
      during usage are not available. eSheaths were measured every 30 mm using a
      digital caliper. Unused 14 F and 16 F eSheaths served as controls. Maximum
      eSheath diameters were measured after insertion of the Edwards Commander Delivery
      System (ECDS) into 14 F and 16 F eSheaths.Finally, eSheaths were retrieved and
      measured after TAVR. Outer diameters of control 14 F eSheaths were 5.8 mm and
      6.50 mm for the 16 F eSheath. Introduction of the 23 mm and 26 mm ECDS into 14 F
      eSheaths showed a maximum diameter of 7.65 mm and 7.64 mm (P = NS). Introduction
      of the 29 mm ECDS into the 16 F eSheath showed the greatest diameter of 8.18 mm
      (P = 0.03). After TAVR, diameters of the 14 F eSheaths were 7.14 mm (23 mm valve)
      and 7.26 mm (26 mm valve) (P = NS), while 16 F eSheaths were 8.10 mm (29 mm
      valve) (P <= 0.03). Nominal 14 F and 16 F eSheaths showed a significant increase
      of the outer diameter during advancement of the ECDS and after TAVR implantation.

PMID- 26000298
TI  - Expression pattern of transcription factors and intracellular cytokines reveals
      that clinically cured tuberculosis is accompanied by an increase in Mycobacterium
      specific Th1, Th2, and Th17 cells.
AB  - Tuberculosis (TB) remains a major global health problem and is the second biggest
      cause of death by infectious disease worldwide. Here, we investigate in vitro the
      Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after
      Mycobacterium-specific antigen stimulation in patients with active pulmonary
      tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a
      positive tuberculin skin test (TST+). Together, our data indicate that clinical
      cure after treatment increases the percentages of Mycobacterium-specific Th1,
      Th2, and Th17 cells compared with those found in active-TB and TST+ healthy
      donors. These results show that the host-parasite equilibrium in latent TB breaks
      in favor of the microorganism and that the subsequent clinical recovery
      posttreatment does not return the percentage levels of such cells to those
      observed in latent tuberculosis. Additionally, our results indicate that rather
      than showing an increase in the percentage of Mycobacterium-specific Tregs,
      active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data,
      together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by
      which the breakdown of the host-parasite equilibrium leads to active-TB and
      changes in the repertoire of Mycobacterium-specific Th cells that are associated
      with clinical cure after treatment of pulmonary tuberculosis.

PMID- 26000299
TI  - Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2
      inhibitor and steroids.
AB  - Patients with osteoarthritis (OA), a condition characterized by cartilage
      degradation, are often treated with steroids, nonsteroidal anti-inflammatory
      drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their
      inhibition of the inflammatory cascade, the drugs affect the balance of matrix
      metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation
      of extracellular matrix (ECM). To compare the effects of these treatments on
      chondrocyte metabolism, TNF-alpha was incubated with cultured chondrocytes to
      mimic a proinflammatory environment with increasing production of MMP-1 and
      prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid
      (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective
      NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2
      production while the nonspecific piroxicam decreased only the latter. Both
      prednisone and celecoxib decreased gene expression of MMP-1 and increased
      expression of aggrecan. Increased gene expression of type II collagen was also
      noted with celecoxib. The nonspecific piroxicam did not show these effects. The
      efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA)
      mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP
      1. In conclusion, this study demonstrates that celecoxib and steroids exert
      similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may
      demonstrate beneficial effects on anabolic metabolism in vivo. 

PMID- 26000300
TI  - Smoldering multiple myeloma.
AB  - Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple
      myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) >= 10%
      and/or M protein level >= 30 g/L in the absence of end organ damage. It
      represents an intermediate stage between monoclonal gammopathy of undetermined
      significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM
      is not uniform, and several parameters have been reported to predict the risk of
      progression. These include the level of M protein and the percentage of BMPC, the
      proportion of immunophenotypically aberrant plasma cells, and the presence of
      immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells
      (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging
      (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So
      far treatment is still not recommended for SMM, because several trials suggested
      that patients with SMM do not benefit from early treatment. However, the Mateos
      et al. trial showed a survival benefit after early treatment with lenalidomide
      plus dexamethasone in patients with high-risk SMM. This trial has prompted a
      reevaluation of early treatment in an asymptomatic patient population. 

PMID- 26000301
TI  - Does moderate intensity exercise attenuate the postprandial lipemic and airway
      inflammatory response to a high-fat meal?
AB  - We investigated whether an acute bout of moderate intensity exercise in the
      postprandial period attenuates the triglyceride and airway inflammatory response
      to a high-fat meal (HFM) compared to remaining inactive in the postprandial
      period. Seventeen (11 M/6 F) physically active (>= 150 min/week of moderate
      vigorous physical activity (MVPA)) subjects were randomly assigned to an exercise
      (EX; 60% VO 2peak) or sedentary (CON) condition after a HFM (10 kcal/kg, 63%
      fat). Blood analytes and airway inflammation via exhaled nitric oxide (eNO) were
      measured at baseline, and 2 and 4 hours after HFM. Airway inflammation was
      assessed with induced sputum and cell differentials at baseline and 4 hours after
      HFM. Triglycerides doubled in the postprandial period (~113 +/- 18%, P < 0.05),
      but the increase did not differ between EX and CON. Percentage of neutrophils was
      increased 4 hours after HFM (~17%), but the increase did not differ between EX
      and CON. Exhaled nitric oxide changed nonlinearly from baseline to 2 and 4 hours
      after HFM (P < 0.05, eta (2) = 0.36). Our findings suggest that, in active
      individuals, an acute bout of moderate intensity exercise does not attenuate the
      triglyceride or airway inflammatory response to a high-fat meal.

PMID- 26000303
TI  - Ciclamilast ameliorates adjuvant-induced arthritis in a rat model.
AB  - We assessed the effect of a novel and selective phosphodiesterase 4 (PDE4)
      inhibitor, ciclamilast, on chronic inflammation in adjuvant-induced arthritis
      (AIA), a rat model of rheumatoid arthritis (RA), and acute inflammation in the
      rat and mouse model of carrageenan-induced paw edema and peritonitis. Our results
      showed that daily oral administration of ciclamilast at 1, 3, and 10 mg/kg dose
      dependently inhibited the increase in hind paw volume of rats with AIA. The
      inhibition of paw edema was associated with inhibition of both the production of
      cytokines such as TNF-alpha, IL-1beta, and IL-6 and cell infiltration assessed in
      subcutaneous paw tissue. Moreover, there was significantly less tissue
      destruction in the ciclamilast-treated rats compared to the vehicle-treated rats,
      as assessed by radiographic analysis and histopathological evaluation. In the two
      acute inflammation models, ciclamilast inhibited carrageenan-induced paw edema in
      rats and inflammatory cell migration into the peritoneal cavity in mice in a dose
      dependent manner. These results not only suggest that ciclamilast, as a disease
      modifying antirheumatic drug (DMARD), can attenuate RA but also provide proof of
      principle that a PDE4 inhibitor may be useful for the treatment of arthritis.

PMID- 26000302
TI  - Vitamin D Deficiency in HIV Infection: Not Only a Bone Disorder.
AB  - Hypovitaminosis D is a worldwide disorder, with a high prevalence in the general
      population of both Western and developing countries. In HIV patients, several
      studies have linked vitamin D status with bone disease, neurocognitive
      impairment, depression, cardiovascular disease, high blood pressure, metabolic
      syndrome, type 2 diabetes mellitus, infections, autoimmune diseases like type 1
      diabetes mellitus, and cancer. In this review, we focus on the most recent
      epidemiological and experimental data dealing with the relationship between
      vitamin D deficiency and HIV infection. We analysed the extent of the problem,
      pathogenic mechanisms, clinical implications, and potential benefits of vitamin D
      supplementation in HIV-infected subjects. 

PMID- 26000304
TI  - Revictimization of violence suffered by those diagnosed with alcohol dependence
      in the general population.
AB  - OBJECTIVE: To verify the association between violence and alcohol dependence
      syndrome in sample populations. METHOD: Population-wide survey with multistage
      probabilistic sample. 3,744 individuals of both genders, aged from 15 to 75
      years, were interviewed from the cities of Sao Paulo and Rio de Janeiro using the
      Composite International Diagnostic Interview (CIDI 2.1). RESULTS: In both cities,
      alcohol dependence was associated with the male gender, having suffered violence
      related to criminality, and having suffered familial violence. In both cities,
      urban violence, in more than 50% of cases, and familial violence, in more than
      90% of cases, preceded alcohol dependence. The reoccurrence of traumatic events
      occurred in more than half of individuals dependent on alcohol. In Sao Paulo,
      having been diagnosed with PTSD is associated with violence revictimization (P =
      0.014; Odds = 3.33). CONCLUSION: Alcohol dependence syndrome is complexly related
      to urban and familial violence in the general population. Violence frequently
      precedes alcoholism, but this relationship is dependent on residence and
      traumatic events. This vicious cycle contributes to perpetuating the high rates
      of alcoholism and violence in the cities. Politicians ordering the reduction of
      violence in the large metropolises can, potentially, reduce alcoholism and
      contribute to the break of this cycle.

PMID- 26000305
TI  - Detecting protein-protein interactions with a novel matrix-based protein sequence
      representation and support vector machines.
AB  - Proteins and their interactions lie at the heart of most underlying biological
      processes. Consequently, correct detection of protein-protein interactions (PPIs)
      is of fundamental importance to understand the molecular mechanisms in biological
      systems. Although the convenience brought by high-throughput experiment in
      technological advances makes it possible to detect a large amount of PPIs, the
      data generated through these methods is unreliable and may not be completely
      inclusive of all possible PPIs. Targeting at this problem, this study develops a
      novel computational approach to effectively detect the protein interactions. This
      approach is proposed based on a novel matrix-based representation of protein
      sequence combined with the algorithm of support vector machine (SVM), which fully
      considers the sequence order and dipeptide information of the protein primary
      sequence. When performed on yeast PPIs datasets, the proposed method can reach
      90.06% prediction accuracy with 94.37% specificity at the sensitivity of 85.74%,
      indicating that this predictor is a useful tool to predict PPIs. Achieved results
      also demonstrate that our approach can be a helpful supplement for the
      interactions that have been detected experimentally. 

PMID- 26000306
TI  - Vitamin D: a review on its effects on muscle strength, the risk of fall, and
      frailty.
AB  - Vitamin D is the main hormone of bone metabolism. However, the ubiquitary nature
      of vitamin D receptor (VDR) suggests potential for widespread effects, which has
      led to new research exploring the effects of vitamin D on a variety of tissues,
      especially in the skeletal muscle. In vitro studies have shown that the active
      form of vitamin D, calcitriol, acts in myocytes through genomic effects involving
      VDR activation in the cell nucleus to drive cellular differentiation and
      proliferation. A putative transmembrane receptor may be responsible for
      nongenomic effects leading to rapid influx of calcium within muscle cells.
      Hypovitaminosis D is consistently associated with decrease in muscle function and
      performance and increase in disability. On the contrary, vitamin D
      supplementation has been shown to improve muscle strength and gait in different
      settings, especially in elderly patients. Despite some controversies in the
      interpretation of meta-analysis, a reduced risk of falls has been attributed to
      vitamin D supplementation due to direct effects on muscle cells. Finally, a low
      vitamin D status is consistently associated with the frail phenotype. This is why
      many authorities recommend vitamin D supplementation in the frail patient. 

PMID- 26000307
TI  - Is vitamin D deficiency related to accumulation of advanced glycation end
      products, markers of inflammation, and oxidative stress in diabetic subjects?
AB  - OBJECTIVES: In diabetes accumulated advanced glycation end products (AGEs) are
      involved in the striking cardiovascular morbidity/mortality. We asked whether a
      hypovitaminosis D associates with an increased formation and toxicity of AGEs in
      diabetes. METHODS: In 276 diabetics (160 M/116 F, age: 65.0 +/- 13.4; 43 type
      1,T1DM, and 233 type 2 patients, T2DM) and 121 nondiabetic controls (60 M/61 F;
      age: 58.6 +/- 15.5 years) routine biochemistry, levels of 25-hydroxyvitamin D3
      (25-(OH)D), skin autofluorescence (SAF), plasma AGE-associated fluorescence (AGE
      FL), N (epsilon) -(carboxymethyl)lysine (CML), soluble receptor for AGEs (sRAGE),
      soluble vascular adhesion protein-1 (sVAP-1), high sensitive C-reactive protein
      (hs-CRP), and renal function (eGFR) were determined. RESULTS: In the diabetics
      SAF and AGE-Fl were higher than those of the controls and correlated with age,
      duration of diabetes, and degree of renal impairment. In T2DM patients but not in
      T1DM the age-dependent rise of SAF directly correlated with hs-CRP and sVAP-1. 25
      (OH)D levels in diabetics and nondiabetics were lowered to a similar degree
      averaging 22.5 ng/mL. No relationship between 25-(OH)D and studied markers except
      for sVAP-1 was observed in the diabetics. CONCLUSION: In diabetics
      hypovitaminosis D does not augment accumulation of AGEs and studied markers of
      microinflammation and oxidative stress except for sVAP-1.

PMID- 26000309
TI  - Late corrective arthrodesis in nonplantigrade diabetic charcot midfoot disease is
      associated with high complication and reoperation rates.
AB  - INTRODUCTION: Charcot arthropathy may lead to a loss of osteoligamentous foot
      architecture and consequently loss of the plantigrade alignment. In this series
      of patients a technique of internal corrective arthrodesis with maximum fixation
      strength was provided in order to lower complication rates. MATERIALS/METHODS: 21
      feet with severe nonplantigrade diabetic Charcot deformity Eichenholtz stages
      II/III (Sanders/Frykberg II/III/IV) and reconstructive arthrodesis with medial
      and additional lateral column support were retrospectively enrolled. Follow-up
      averaged 4.0 years and included a clinical (AOFAS score/PSS), radiological, and
      complication analysis. RESULTS: A mean of 2.4 complications/foot occurred, of
      which 1.5/foot had to be solved surgically. 76% of feet suffered from soft tissue
      complications; 43% suffered hardware-associated complications. Feet with only 2
      out of 5 high risk criteria according to Pinzur showed significantly lower
      complication counts. Radiographs revealed a correct restoration of all foot axes
      postoperatively with superior fixation strength medially. CONCLUSION: Late
      corrective arthrodesis with medial and lateral column stabilization in the
      nonplantigrade stages of neuroosteoarthropathy can provide reasonable
      reconstruction of the foot alignment. Nonetheless, overall
      complication/reoperation rates were high. With separation into low/high risk
      criteria a helpful guide in treatment choice is provided. This trial is
      registered with German Clinical Trials Register (DRKS) under number DRKS00007537.

PMID- 26000308
TI  - The pleiotropic effects of vitamin D in gynaecological and obstetric diseases: an
      overview on a hot topic.
AB  - The traditionally recognized role of vitamin D consists in the regulation of bone
      metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and
      in vivo studies recognized several "noncalcemic" effects of vitamin D
      metabolites. Accumulating evidence suggests that the metabolic pathways of this
      vitamin may play a key role in the developing of gynaecological/obstetric
      diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply)
      affect the risk of several gynaecological diseases, such as polycystic ovary
      syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other
      hand, since also the maternal-fetal unit is under the influence of vitamin D, a
      breakdown in its homeostasis may underlie infertility, preeclampsia, and
      gestational diabetes mellitus (GDM). According to our literature review, the
      relationship between vitamin D and gynaecological/obstetric diseases must be
      replicated in future studies which could clarify the molecular machineries behind
      their development. We suggest that further investigation should take into account
      the different serum levels of this vitamin, the several actions which arise from
      the binding between it and its receptor (taking into account its possible
      polymorphism), and finally the interplay between vitamin D metabolism and other
      hormonal and metabolic pathways. 

PMID- 26000311
TI  - Muramyl dipeptide enhances lipopolysaccharide-induced osteoclast formation and
      bone resorption through increased RANKL expression in stromal cells.
AB  - Lipopolysaccharide (LPS) is bacterial cell wall component capable of inducing
      osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP),
      the minimal essential structural unit responsible for the immunological activity
      of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we
      investigated the effect of MDP in LPS-induced osteoclast formation and bone
      resorption. LPS was administered with or without MDP into the supracalvariae of
      mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate
      resistant acid phosphatase (TRAP), the ratio of the bone destruction area, the
      level of tartrate-resistant acid phosphatase form 5b (TRACP 5b), and C-terminal
      telopeptides fragments of type I collagen as a marker of bone resorption in mice
      administrated both LPS and MDP were higher than those in mice administrated LPS
      or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in
      parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor
      activator of NF-kappaB ligand (RANKL) expression and Toll-like receptor 4 (TLR4)
      expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced
      mitogen-activated protein kinase (MAPK) signaling, including ERK, p38, and JNK,
      in stromal cells. These results suggest that MDP might play an important role in
      pathological bone resorption in bacterial infection diseases. 

PMID- 26000310
TI  - Bone-immune cell crosstalk: bone diseases.
AB  - Bone diseases are associated with great morbidity; thus, the understanding of the
      mechanisms leading to their development represents a great challenge to improve
      bone health. Recent reports suggest that a large number of molecules produced by
      immune cells affect bone cell activity. However, the mechanisms are incompletely
      understood. This review aims to shed new lights into the mechanisms of bone
      diseases involving immune cells. In particular, we focused our attention on the
      major pathogenic mechanism underlying periodontal disease, psoriatic arthritis,
      postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic
      solid tumors, and multiple myeloma. 

PMID- 26000313
TI  - The alteration and clinical significance of Th22/Th17/Th1 cells in patients with
      chronic myeloid leukemia.
AB  - T helper- (Th-) cell immunodeficiency plays important roles in tumor development
      and their effects in chronic myeloid leukemia (CML) remain unclear. In the
      present study, we mainly investigated the role of Th22, Th17, and Th1 cell and
      their related cytokines (IL-22, IL-17, and IFN-r) in the pathophysiology of CML.
      Bone marrow (BM) and peripheral blood (PB) were extracted from newly diagnosed
      (ND), chronic phase- (CP-) CML patients, and controls. Th subsets were examined
      by flow cytometry. Plasma IL-22, IL-17, and IFN-r concentrations were measured by
      ELISA. AHR and RORC mRNA expressions were examined by RT-PCR. The frequencies of
      Th22, Th17, and Th1 cells, along with the expression of specific transcription
      factors RORC and AHR, were significantly decreased in ND patients compared with
      healthy controls, while all these abnormality recovered in CP patients. In
      addition, there existed a significantly positive relationship between Th22 and
      Th17 cells in PB or BM. A significantly negative relationship was found between
      Th cells (Th22, Th17, or Th1) and BCR-ABL (%) IS or the number of PB white blood
      cells. All these results demonstrated that Th22, Th17, and Th1 cells might be
      important therapeutic targets in CML and could facilitate a better outcome for
      tumor immunotherapy. 

PMID- 26000312
TI  - Human myeloma cell lines induce osteoblast downregulation of CD99 which is
      involved in osteoblast formation and activity.
AB  - CD99 is a transmembrane glycoprotein expressed in physiological conditions by
      cells of different tissues, including osteoblasts (OBs). High or low CD99 levels
      have been detected in various pathological conditions, and the supernatant of
      some carcinoma cell lines can modulate CD99 expression in OB-like cells. In the
      present work we demonstrate for the first time that two different human myeloma
      cell lines (H929 and U266) and, in a less degree, their conditioned media
      significantly downregulate CD99 expression in normal human OBs during the
      differentiation process. In the same experimental conditions the OBs display a
      less differentiated phenotype as demonstrated by the decreased expression of
      RUNX2 and Collagen I. On the contrary, when CD99 was activated by using a
      specific agonist antibody, the OBs become more active as demonstrated by the
      upregulation of Alkaline Phosphatase, Collagen I, RUNX2, and JUND expression.
      Furthermore, we demonstrate that the activation of CD99 is able to induce the
      phosphorylation of ERK 1/2 and AKT intracellular signal transduction molecules in
      the OBs. 

PMID- 26000314
TI  - Hair follicle dermal sheath derived cells improve islet allograft survival
      without systemic immunosuppression.
AB  - Immunosuppressive drugs successfully prevent rejection of islet allografts in the
      treatment of type I diabetes. However, the drugs also suppress systemic immunity
      increasing the risk of opportunistic infection and cancer development in
      allograft recipients. In this study, we investigated a new treatment for
      autoimmune diabetes using naturally immune privileged, hair follicle derived,
      autologous cells to provide localized immune protection of islet allotransplants.
      Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle
      dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the
      kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6
      recipients. Group 1 allografts survived significantly longer than group 2 (32.2
      +/- 12.2 versus 14.1 +/- 3.3 days, P < 0.001) without administration of any
      systemic immunosuppressive agents. DSCC reduced T cell activation in the renal
      lymph node, prevented graft infiltrates, modulated inflammatory chemokine and
      cytokine profiles, and preserved better beta cell function in the islet
      allografts, but no systemic immunosuppression was observed. In summary, DSCC
      prolong islet allograft survival without systemic immunosuppression by local
      modulation of alloimmune responses, enhancing of beta cell survival, and
      promoting of graft revascularization. This novel finding demonstrates the
      capacity of easily accessible hair follicle cells to be used as local
      immunosuppression agents in islet transplantation. 

PMID- 26000316
TI  - Immune disorders in Hashimoto's thyroiditis: what do we know so far?
AB  - This review of literature attempts to identify the factors that are involved in
      the pathogenesis of Hashimoto thyroiditis, an immune defect in an individual with
      genetic susceptibility accompanied with environmental factors. The frequency of
      Hashimoto's disease is a growing trend and among Caucasians it is estimated at
      approximately 5%. The dysfunction of the gland may be clinically evident (0.1-2%
      of the population) or subclinical (10-15%). The pathology is diagnosed five to
      ten times more often in women than men and its incidence increases with the age
      (the peak of the number of cases is between 45 and 65); however, it can also be
      diagnosed in children. The pathogenesis of Hashimoto's thyroiditis is still not
      fully comprehended. In the etiology of Hashimoto thyroiditis excessively
      stimulated T CD4+ cells are known to play the most important role. Recent
      research has demonstrated an increasing role of newly discovered cells such as
      Th17 (CD4+IL-17+) or T regulatory cells (CD4+CD25+(high)FoxP3+) in the induction
      of autoimmune disorders. The process of programmed cell death also plays an
      equally important role in the pathogenesis and the development of hypothyroidism.

PMID- 26000317
TI  - A Persistent Disparity: Smoking in Rural Sexual and Gender Minorities.
AB  - PURPOSE: Sexual and gender minorities (SGM) smoke cigarettes at higher rates than
      the general population. Historically, research in SGM health issues was conducted
      in urban populations and recent population-based studies seldom have sufficient
      SGM participants to distinguish urban from rural. Given that rural populations
      also tend to have a smoking disparity, and that many SGM live in rural areas, it
      is vitally important to understand the intersection of rural residence, SGM
      identity, and smoking. This study analyzes the patterns of smoking in urban and
      rural SGM in a large sample. METHODS: We conducted an analysis of 4280 adult
      participants in the Out, Proud, and Healthy project with complete data on SGM
      status, smoking status, and zip code. Surveys were conducted at 6 Missouri Pride
      Festivals and online in 2012. Analysis involved descriptive and bivariate
      methods, and multivariable logistic regression. We used GIS mapping to
      demonstrate the dispersion of rural SGM participants. RESULTS: SGM had higher
      smoking proportion than the non-SGM recruited from these settings. In the
      multivariable model, SGM identity conferred 1.35 times the odds of being a
      current smoker when controlled for covariates. Rural residence was not
      independently significant, demonstrating the persistence of the smoking disparity
      in rural SGM. Mapping revealed widespread distribution of SGM in rural areas.
      CONCLUSION: The SGM smoking disparity persists among rural SGM. These communities
      would benefit from continued research into interventions targeting both SGM and
      rural tobacco control measures. Recruitment at Pride Festivals may provide a
      venue for reaching rural SGM for intervention.

PMID- 26000315
TI  - Interactions between MSCs and immune cells: implications for bone healing.
AB  - It is estimated that, of the 7.9 million fractures sustained in the United States
      each year, 5% to 20% result in delayed or impaired healing requiring therapeutic
      intervention. Following fracture injury, there is an initial inflammatory
      response that plays a crucial role in bone healing; however, prolonged
      inflammation is inhibitory for fracture repair. The precise spatial and temporal
      impact of immune cells and their cytokines on fracture healing remains obscure.
      Some cytokines are reported to be proosteogenic while others inhibit bone
      healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an
      attractive option for augmenting the fracture repair process. Osteoprogenitor
      MSCs not only differentiate into bone, but they also exert modulatory effects on
      immune cells via a variety of mechanisms. In this paper, we review the current
      literature on both in vitro and in vivo studies on the role of the immune system
      in fracture repair, the use of MSCs in the enhancement of fracture healing, and
      interactions between MSCs and immune cells. Insight into this paradigm can
      provide valuable clues in identifying cellular and noncellular targets that can
      potentially be modulated to enhance both natural bone healing and bone repair
      augmented by the exogenous addition of MSCs. 

PMID- 26000318
TI  - Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
AB  - OBJECTIVE: Novel treatments such as natalizumab and fingolimod achieve their
      therapeutic efficacy in multiple sclerosis (MS) by blocking access of subsets of
      immune cells into the central nervous system, thus creating nonphysiological
      intrathecal immunity. In contrast, daclizumab, a humanized monoclonal antibody
      against the alpha chain of the IL-2 receptor, has a unique mechanism of action
      with multiple direct effects on innate immunity. As cellular intrathecal
      abnormalities corresponding to MS have been well defined, we asked how daclizumab
      therapy affects these immunological hallmarks of the MS disease process. METHODS:
      Nineteen subpopulations of immune cells were assessed in a blinded fashion in the
      blood and 50-fold concentrated cerebrospinal fluid (CSF) cell pellet in 32
      patients with untreated relapsing-remitting MS (RRMS), 22 daclizumab-treated RRMS
      patients, and 11 healthy donors (HDs) using 12-color flow cytometry. RESULTS:
      Long-term daclizumab therapy normalized all immunophenotyping abnormalities
      differentiating untreated RRMS patients from HDs. Specifically, strong enrichment
      of adaptive immune cells (CD4+ and CD8+ T cells and B cells) in the CSF was
      reversed. Similarly, daclizumab controlled MS-related increases in the innate
      lymphoid cells (ILCs) and lymphoid tissue inducer cells in the blood and CSF, and
      reverted the diminished proportion of intrathecal monocytes. The only marker that
      distinguished daclizumab-treated MS patients from HDs was the expansion of
      immunoregulatory CD56(bright) NK cells. INTERPRETATION: Normalization of
      immunological abnormalities associated with MS by long-term daclizumab therapy
      suggests that this drug's effects on ILCs, NK cells, and dendritic cell-mediated
      antigen presentation to CD4+ and CD8+ T cells are critical in regulating the MS
      disease process.

PMID- 26000319
TI  - Abnormal cortical thickness connectivity persists in childhood absence epilepsy.
AB  - OBJECTIVE: Childhood absence epilepsy (CAE) is a childhood-onset generalized
      epilepsy. Recent fMRI studies have suggested that frontal cortex activity occurs
      before thalamic involvement in epileptic discharges suggesting that frontal
      cortex may play an important role in childhood absence seizures. Neurocognitive
      deficits can persist after resolution of the epilepsy. We investigate whether
      structural connectivity changes are present in the brains of CAE patients in
      young adulthood. METHODS: Cortical thickness measurements were obtained for 30
      subjects with CAE (mean age 21 +/- 2 years) and 56 healthy controls (mean age 24
      +/- 4) and regressed for age, sex, and total intracranial volume (TIV).
      Structural connectivity was evaluated by measuring the correlation between
      average cortical thicknesses in 915 regions over the brain. Maps of connectivity
      strength were then obtained for both groups. RESULTS: When compared to controls,
      the CAE group shows overall increased "connectivity" with focal increased
      connection strength in anterior regions including; the anterior cingulate and the
      insula and superior temporal gyrus bilaterally; the right orbito-frontal and
      supramarginal regions; and the left entorhinal cortex. Decreased connection
      strength in the CAE group was found in the left occipital lobe, with a similar
      trend in right occipital lobe. INTERPRETATION: Brains in young adults whose CAE
      was resolved had abnormal structural connectivity. Our findings suggest that
      frontal regions correlate most with cortical thickness throughout the brain in
      CAE patients, whereas occipital regions correlate most in well matched normal
      controls. We interpret this as evidence of a developmental difference in CAE that
      emphasizes these frontal lobe regions, perhaps driven by frontal lobe
      epileptiform activity.

PMID- 26000320
TI  - Double-blind, placebo-controlled study of HGF gene therapy in diabetic
      neuropathy.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a plasmid (VM202) containing
      two human hepatocyte growth factor isoforms given by intramuscular injections in
      patients with painful diabetic neuropathy. METHODS: In a double-blind, placebo
      controlled study, patients were randomized to receive injections of 8 or 16 mg
      VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14.
      The prospective primary outcome was change in the mean pain score measured by a 7
      day pain diary. Secondary outcomes included a responder analysis, quality of life
      and pain measures, and intraepidermal nerve fiber density. RESULTS: There were no
      significant adverse events attributable to VM202. Eighty-four patients completed
      the study. Patients receiving 8 mg VM202 per leg improved the most in all
      efficacy measures including a significant (P = 0.03) reduction at 3 months in the
      mean pain score and continued but not statistically significant reductions in
      pain at 6 and 9 months. Of these patients, 48.4% experienced a >=50% reduction in
      pain compared to 17.6% of placebo patients. There were also significant
      improvements in the brief pain inventory for patients with diabetic peripheral
      neuropathy and the questionnaire portion of the Michigan Neuropathy Screening
      Instrument. Patients not on pregabalin or gabapentin had the largest reductions
      in pain. INTERPRETATION: VM202 was safe, well tolerated and effective indicating
      the feasibility of a nonviral gene therapy approach to painful diabetic
      neuropathy. Two days of treatment were sufficient to provide symptomatic relief
      with improvement in quality of life for 3 months. VM202 may be particularly
      beneficial for patients not taking gabapentin or pregabalin.

PMID- 26000321
TI  - Predictors of disability worsening in clinically isolated syndrome.
AB  - OBJECTIVE: To assess demographic, clinical, magnetic resonance imaging, and
      treatment exposure predictors of time to 3 or 12-month confirmed disability
      worsening in clinically isolated syndrome (CIS) and early multiple sclerosis
      (MS). METHODS: We utilized the MSBase Incident Study (MSBasis), a prospective
      cohort study of outcome after CIS. Predictors of time to first 3 and 12-month
      confirmed expanded disability status scale worsening were analyzed using Cox
      proportional hazards regression. RESULTS: About 1989 patients were analyzed, the
      largest seen-from-onset cohort reported to-date. A total of 391 patients had a
      first 3-month confirmed disability worsening event, of which 307 were sustained
      for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06,
      1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI
      1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18,
      1.22), and lower proportion of observation time on treatment were associated with
      3-month confirmed worsening. Predictors of time to 12-month sustained worsening
      included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05,
      1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater
      proportion of follow-up time exposed to treatment was associated with greater
      reductions in the rate of worsening. INTERPRETATION: This study provides class IV
      evidence for a strong protective effect of disease-modifying treatment to reduce
      disability worsening events in patients with CIS and early MS, and confirms age
      and pyramidal dysfunction at onset as risk factors.

PMID- 26000323
TI  - Stroke etiology is associated with outcome in posterior circulation stroke.
AB  - OBJECTIVE: Stroke research and clinical trials have focused mainly on anterior
      circulation stroke (ACS). Since clinical characteristics, mechanisms, and
      outcomes of posterior circulation stroke (PCS) have been reported different from
      ACS, more PCS studies are required, particularly researching the etiologies, to
      help establish an optimal management strategy. METHODS: The present study
      analyzed patients of PCS who were consecutively admitted and registered in Taipei
      Veterans General Hospital Stroke Registry between 1 January 2012 to 28 February
      2014. We demonstrated the distribution of etiologies, compared the clinical
      characteristics/outcomes among different etiology groups, and used
      univariate/multivariate analyses to identify the predictors for poor functional
      outcome (modified Rankin Scale >=5) at discharge and 3 month. RESULTS: About 286
      patients of PCS were included for analyses. Basilar artery atheromatous branch
      occlusive disease (BABO, 28.0%) and large artery dissection (25.9%) were the two
      most common etiologies, followed by large artery atherosclerotic
      stenosis/occlusion (LAA, 20.6%), cardioembolism (CE, 18.5%) and small vessel
      disease (7.0%). Age, vascular risk factors, infarct locations and patterns, and
      outcomes were different among these five etiology groups. Multivariate analyses
      showed that age >70 y/o (discharge/3 month, OR, 95% CI: 3.05, 1.23-7.56/8.39,
      2.32-30.33), admission NIH Stroke Scale >9 (19.50, 8.69-43.75/13.45, 5.59-32.39),
      and etiology (LAA versus BABO: 5.00, 1.58-15.83/4.00, 1.19-13.4; CE versus BABO:
      3.36, 1.02-11.09/4.66, 1.40-15.46) were independently associated with poor
      functional outcome. INTERPRETATION: The etiologies of PCS are heterogeneous and
      shown to be associated with functional outcomes. Our results have shed lights on
      future pathophysiological research and designs of clinical trials for PCS.

PMID- 26000322
TI  - Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.
AB  - OBJECTIVE: Short-chain enoyl-CoA hydratase (ECHS1) is a multifunctional
      mitochondrial matrix enzyme that is involved in the oxidation of fatty acids and
      essential amino acids such as valine. Here, we describe the broad phenotypic
      spectrum and pathobiochemistry of individuals with autosomal-recessive ECHS1
      deficiency. METHODS: Using exome sequencing, we identified ten unrelated
      individuals carrying compound heterozygous or homozygous mutations in ECHS1.
      Functional investigations in patient-derived fibroblast cell lines included
      immunoblotting, enzyme activity measurement, and a palmitate loading assay.
      RESULTS: Patients showed a heterogeneous phenotype with disease onset in the
      first year of life and course ranging from neonatal death to survival into
      adulthood. The most prominent clinical features were encephalopathy (10/10),
      deafness (9/9), epilepsy (6/9), optic atrophy (6/10), and cardiomyopathy (4/10).
      Serum lactate was elevated and brain magnetic resonance imaging showed white
      matter changes or a Leigh-like pattern resembling disorders of mitochondrial
      energy metabolism. Analysis of patients' fibroblast cell lines (6/10) provided
      further evidence for the pathogenicity of the respective mutations by showing
      reduced ECHS1 protein levels and reduced 2-enoyl-CoA hydratase activity. While
      serum acylcarnitine profiles were largely normal, in vitro palmitate loading of
      patient fibroblasts revealed increased butyrylcarnitine, unmasking the functional
      defect in mitochondrial beta-oxidation of short-chain fatty acids. Urinary
      excretion of 2-methyl-2,3-dihydroxybutyrate - a potential derivative of acryloyl
      CoA in the valine catabolic pathway - was significantly increased, indicating
      impaired valine oxidation. INTERPRETATION: In conclusion, we define the
      phenotypic spectrum of a new syndrome caused by ECHS1 deficiency. We speculate
      that both the beta-oxidation defect and the block in l-valine metabolism, with
      accumulation of toxic methacrylyl-CoA and acryloyl-CoA, contribute to the
      disorder that may be amenable to metabolic treatment approaches.

PMID- 26000324
TI  - Sulfatide levels correlate with severity of neuropathy in metachromatic
      leukodystrophy.
AB  - OBJECTIVE: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal
      storage disorder due to deficient activity of arylsulfatase A (ASA) that causes
      accumulation of sulfatide and lysosulfatide. The disorder is associated with
      demyelination and axonal loss in the central and peripheral nervous systems. The
      late infantile form has an early-onset, rapidly progressive course with severe
      sensorimotor dysfunction. The relationship between the degree of nerve damage and
      (lyso)sulfatide accumulation is, however, not established. METHODS: In 13
      children aged 2-5 years with severe motor impairment, markedly elevated
      cerebrospinal fluid (CSF) and sural nerve sulfatide and lysosulfatide levels,
      genotype, ASA mRNA levels, residual ASA, and protein cross-reactive immunological
      material (CRIM) confirmed the diagnosis. We studied the relationship between
      (lyso)sulfatide levels and (1) the clinical deficit in gross motor function (GMFM
      88), (2) median and peroneal nerve motor and median and sural nerve sensory
      conduction studies (NCS), (3) median and tibial nerve somatosensory evoked
      potentials (SSEPs), (4) sural nerve histopathology, and (5) brain MR
      spectroscopy. RESULTS: Eleven patients had a sensory-motor demyelinating
      neuropathy on electrophysiological testing, whereas two patients had normal
      studies. Sural nerve and CSF (lyso)sulfatide levels strongly correlated with
      abnormalities in electrophysiological parameters and large myelinated fiber loss
      in the sural nerve, but there were no associations between (lyso)sulfatide levels
      and measures of central nervous system (CNS) involvement (GMFM-88 score, SSEP,
      and MR spectroscopy). INTERPRETATION: Nerve and CSF sulfatide and lysosulfatide
      accumulation provides a marker of disease severity in the PNS only; it does not
      reflect the extent of CNS involvement by the disease process. The magnitude of
      the biochemical disturbance produces a continuously graded spectrum of
      impairments in neurophysiological function and sural nerve histopathology.

PMID- 26000325
TI  - Biomarkers and cognitive endpoints to optimize trials in Alzheimer's disease.
AB  - OBJECTIVE: To find the combination of candidate biomarkers and cognitive
      endpoints to maximize statistical power and minimize cost of clinical trials of
      healthy elders at risk for cognitive decline due to Alzheimer's disease. METHODS:
      Four-hundred and twelve cognitively normal participants were followed over 7
      years. Nonlinear methods were used to estimate the longitudinal trajectories of
      several cognitive outcomes including delayed memory recall, executive function,
      processing speed, and several cognitive composites by subgroups selected on the
      basis of biomarkers, including APOE-epsilon4 allele carriers, cerebrospinal fluid
      biomarkers (Abeta 42, total tau, and phosphorylated tau), and those with small
      hippocampi. RESULTS: Derived cognitive composites combining Alzheimer's Disease
      Assessment Scale (ADAS)-cog scores with additional delayed memory recall and
      executive function components captured decline more robustly across biomarker
      groups than any measure of a single cognitive domain or ADAS-cog alone.
      Substantial increases in power resulted when including only participants positive
      for three or more biomarkers in simulations of clinical trials. INTERPRETATION:
      Clinical trial power may be improved by selecting participants on the basis of
      amyloid and neurodegeneration biomarkers and carefully tailoring primary
      cognitive endpoints to reflect the expected decline specific to these
      individuals.

PMID- 26000326
TI  - The cognitive profile of prion disease: a prospective clinical and imaging study.
AB  - OBJECTIVES: Prion diseases are dementing illnesses with poorly defined
      neuropsychological features. This is probably because the most common form,
      sporadic Creutzfeldt-Jakob disease, is often rapidly progressive with pervasive
      cognitive decline making detailed neuropsychological investigation difficult.
      This study, which includes patients with inherited, acquired (iatrogenic and
      variant) and sporadic forms of the disease, is the only large-scale
      neuropsychological investigation of this patient group ever undertaken and aimed
      to define a neuropsychological profile of human prion diseases. METHODS: A
      tailored short cognitive examination of all of the patients (n = 81), with
      detailed neuropsychological testing in a subset with mild disease (n = 30) and
      correlation with demographic, clinical, genetic (PRNP mutation and polymorphic
      codon 129 genotype), and other variables (MRI brain signal change in cortex,
      basal ganglia or thalamus; quantitative research imaging, cerebrospinal fluid 14
      3-3 protein). RESULTS: Comparison with healthy controls showed patients to be
      impaired on all tasks. Principal components analysis showed a major axis of
      fronto-parietal dysfunction that accounted for approximately half of the variance
      observed. This correlated strongly with volume reduction in frontal and parietal
      gray matter on MRI. Examination of individual patients' performances confirmed
      early impairment on this axis, suggesting characteristic cognitive features in
      mild disease: prominent executive impairment, parietal dysfunction, a largely
      expressive dysphasia, with reduced motor speed. INTERPRETATION: Taken together
      with typical neurological features, these results complete a profile that should
      improve differential diagnosis in a clinical setting. We propose a tailored
      neuropsychological battery for early recognition of clinical onset of symptoms
      with potential for use in clinical trials involving at-risk individuals.

PMID- 26000327
TI  - Epilepsy, cognitive deficits and neuroanatomy in males with ZDHHC9 mutations.
AB  - OBJECTIVE: Systematic investigation of individuals with intellectual disability
      after genetic diagnosis can illuminate specific phenotypes and mechanisms
      relevant to common neurodevelopmental disorders. We report the neurological,
      cognitive and neuroanatomical characteristics of nine males from three families
      with loss-of-function mutations in ZDHHC9 (OMIM #300799). METHODS: All known
      cases of X-linked intellectual disability (XLID) due to ZDHHC9 mutation in the
      United Kingdom were invited to participate in a study of neurocognitive and
      neuroimaging phenotypes. RESULTS: Seven out of nine males with ZDHHC9 mutations
      had been diagnosed with epilepsy, exceeding epilepsy risk in XLID comparison
      subjects (P = 0.01). Seizure histories and EEG features amongst ZDHHC9 mutation
      cases shared characteristics with rolandic epilepsy (RE). Specific cognitive
      deficits differentiated males with ZDHHC9 mutations from XLID comparison subjects
      and converged with reported linguistic and nonlinguistic deficits in idiopathic
      RE: impaired oromotor control, reduced verbal fluency, and impaired inhibitory
      control on visual attention tasks. Consistent neuroanatomical abnormalities
      included thalamic and striatal volume reductions and hypoplasia of the corpus
      callosum. INTERPRETATION: Mutations in ZDHHC9 are associated with susceptibility
      to focal seizures and specific cognitive impairments intersecting with the RE
      spectrum. Neurocognitive deficits are accompanied by consistent abnormalities of
      subcortical structures and inter-hemispheric connectivity. The biochemical,
      cellular and network-level mechanisms responsible for the ZDHHC9-associated
      neurocognitive phenotype may be relevant to cognitive outcomes in RE.

PMID- 26000328
TI  - CD4 cell response to interval therapy with natalizumab.
AB  - Natalizumab treatment alters peripheral CD4 cells counts in multiple sclerosis
      (MS) patients, providing a way to monitor the pharmacodynamic effects of the
      drug. The study was undertaken to assess whether CD4 cell counts correlate with
      different phases of natalizumab treatment of relapsing MS patients, including
      during a 12-week planned treatment interruption, and whether that might provide
      insights on lymphocyte trafficking. Clinical outcomes, MRI data, and CD4 cell
      counts were assessed at baseline prior to initiating natalizumab, while on
      regular dosing, at the end of the 12-week extended dosing interval, and at the
      time of reinitiation of natalizumab. The 12-week interruption was well tolerated
      and not associated with return of MS activity, disability progression, or new or
      worsened MRI data. Observed significant shifts in CD4 counts - dramatically
      increasing from the baseline while on treatment and decreasing back to the
      baseline level off treatment, then rising in a similar manner on natalizumab
      reinitiation, suggest that these measurements may aid in monitoring modulation of
      lymphocyte trafficking and cell redistribution. 

PMID- 26000329
TI  - Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5.
AB  - Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal
      epilepsy secondary to extensive type IIA focal cortical dysplasia identified a
      paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This
      variant has previously been reported to cause familial focal epilepsy with
      variable foci in patients with normal brain imaging. Immunostaining of resected
      brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR)
      activation. This report shows the histopathological features of cortical
      dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the
      malformed tissue and expands the spectrum of neurological manifestations of
      DEPDC5 mutations to include severe phenotypes with large areas of cortical
      malformation. 

PMID- 26000330
TI  - The primate autoimmune encephalomyelitis model; a bridge between mouse and man.
AB  - INTRODUCTION: Multiple sclerosis (MS) is an enigmatic autoimmune-driven
      inflammatory/demyelinating disease of the human central nervous system (CNS),
      affecting brain, spinal cord, and optic nerves. The cause of the disease is not
      known and the number of effective treatments is limited. Despite some clear
      successes, translation of immunological discoveries in the mouse experimental
      autoimmune encephalomyelitis (EAE) model into effective therapies for MS patients
      has been difficult. This translation gap between MS and its elected EAE animal
      model reflects the phylogenetic distance between humans and their experimental
      counterpart, the inbred/specific pathogen free (SPF) laboratory mouse. OBJECTIVE:
      Here, we discuss that important new insights can be obtained into the mechanistic
      basis of the therapy paradox from the study of nonhuman primate EAE (NHP-EAE)
      models, the well-validated EAE model in common marmosets (Callithrix jacchus) in
      particular. INTERPRETATION: Data presented in this review demonstrate that due to
      a considerable immunological and pathological overlap with mouse EAE on one side
      and MS on the other, the NHP EAE model can help us bridge the translation gap.

PMID- 26000332
TI  - Adaptation of ovarian cancer cells to the peritoneal environment: Multiple
      mechanisms of the developmental patterning gene HOXA9.
AB  - The lethality of ovarian cancer stems from its propensity to involve the
      peritoneal cavity. However, the mechanisms that enable ovarian cancer cells to
      readily adapt to the peritoneal environment are not well understood. Here, we
      describe our recent studies in which we identified the mechanisms by which the
      transcription factor encoded by the patterning gene HOXA9 promotes the aggressive
      behavior of ovarian cancer. Firstly, we identified that HOXA9 promotes ovarian
      tumor growth and angiogenesis by activating the gene encoding transforming growth
      factor-beta2 (TGF-beta2), which in turn stimulates peritoneal fibroblasts and
      mesenchymal stem cells to acquire features of cancer-associated fibroblasts.
      Secondly, by inducing TGF-beta2 and chemokine (C-C motif) ligand 2, HOXA9
      stimulates peritoneal macrophages to acquire an immunosuppressive phenotype.
      Thirdly, HOXA9 stimulates attachment of ovarian cancer cells to peritoneal
      mesothelial cells by inducing expression of P-cadherin. By inducing P-cadherin,
      HOXA9 also enables floating cancer cells in the peritoneal cavity to form
      aggregates and escape anoikis. Together, our studies demonstrate that HOXA9
      enables ovarian cancer cells to adapt to the peritoneal environment and
      'educates' different types of stromal cells to become permissive for tumor
      growth. Our studies provide new insights into the regulation of tumor-stroma
      interactions in ovarian cancer and implicate several key effector molecules as
      candidate therapeutic targets.

PMID- 26000335
TI  - Generating personalized web search using semantic context.
AB  - The "one size fits the all" criticism of search engines is that when queries are
      submitted, the same results are returned to different users. In order to solve
      this problem, personalized search is proposed, since it can provide different
      search results based upon the preferences of users. However, existing methods
      concentrate more on the long-term and independent user profile, and thus reduce
      the effectiveness of personalized search. In this paper, the method captures the
      user context to provide accurate preferences of users for effectively
      personalized search. First, the short-term query context is generated to identify
      related concepts of the query. Second, the user context is generated based on the
      click through data of users. Finally, a forgetting factor is introduced to merge
      the independent user context in a user session, which maintains the evolution of
      user preferences. Experimental results fully confirm that our approach can
      successfully represent user context according to individual user information
      needs. 

PMID- 26000336
TI  - Microalgae for bioenergy: key technology nodes.
AB  - Microalgae have increasingly gained research interest as a source of lipids for
      biodiesel production. The wet way processing of harvested microalgae was
      suggested and evaluated with respect to the possible environmental impacts and
      production costs. This study is focused on the three key steps of the suggested
      process: flocculation, water recycling, and extraction of lipids. Microalgae
      strains with high content of lipids were chosen for cultivation and subsequent
      treatment process. Ammonium hydroxide was tested as the flocculation agent and
      its efficiency was compared with chitosan. Determined optimal flocculation
      conditions for ammonium hydroxide enable the water recycling for the recurring
      microalgae growth, which was verified for the use of 30, 50, and 80% recycled
      water. For extraction of the wet microalgae hexane, hexane/ethanol and
      comparative chloroform/methanol systems were applied. The efficiency of
      hexane/ethanol extraction system was found as comparable with chloroform/methanol
      system and it seems to be promising owing to its low volatility and toxicity and
      mainly the low cost. 

PMID- 26000337
TI  - Improved algorithm for analysis of DNA sequences using multiresolution
      transformation.
AB  - Bioinformatics and genomic signal processing use computational techniques to
      solve various biological problems. They aim to study the information allied with
      genetic materials such as the deoxyribonucleic acid (DNA), the ribonucleic acid
      (RNA), and the proteins. Fast and precise identification of the protein coding
      regions in DNA sequence is one of the most important tasks in analysis. Existing
      digital signal processing (DSP) methods provide less accurate and computationally
      complex solution with greater background noise. Hence, improvements in accuracy,
      computational complexity, and reduction in background noise are essential in
      identification of the protein coding regions in the DNA sequences. In this paper,
      a new DSP based method is introduced to detect the protein coding regions in DNA
      sequences. Here, the DNA sequences are converted into numeric sequences using
      electron ion interaction potential (EIIP) representation. Then discrete wavelet
      transformation is taken. Absolute value of the energy is found followed by proper
      threshold. The test is conducted using the data bases available in the National
      Centre for Biotechnology Information (NCBI) site. The comparative analysis is
      done and it ensures the efficiency of the proposed system. 

PMID- 26000334
TI  - Experimental Models of Inflammatory Bowel Diseases.
AB  - The understanding of the intestinal inflammation occurring in the inflammatory
      bowel diseases (IBD) has been immeasurably advanced by the development of the now
      numerous murine models of intestinal inflammation. The usefulness of this
      research tool in IBD studies has been enabled by our improved knowledge of
      mucosal immunity and thus our improved ability to interpret the complex responses
      of mice with various causes of colitis; in addition, it has been powered by the
      availability of models in which the mice have specific genetic and/or immunologic
      defects that can be related to the origin of the inflammation. Finally, and more
      recently, it has been enhanced by our newly acquired ability to define the
      intestinal microbiome under various conditions and thus to understand how
      intestinal microorganisms impact on inflammation. In this brief review of murine
      models of intestinal inflammation we focus mainly on the most often used models
      that are, not incidentally, also the models that have yielded major insights into
      IBD pathogenesis.

PMID- 26000333
TI  - Strategies to minimize hypertrophy in cartilage engineering and regeneration.
AB  - Due to a blood supply shortage, articular cartilage has a limited capacity for
      self-healing once damaged. Articular chondrocytes, cartilage progenitor cells,
      embryonic stem cells, and mesenchymal stem cells are candidate cells for
      cartilage regeneration. Significant current attention is paid to improving
      chondrogenic differentiation capacity; unfortunately, the potential chondrogenic
      hypertrophy of differentiated cells is largely overlooked. Consequently, the
      engineered tissue is actually a transient cartilage rather than a permanent one.
      The development of hypertrophic cartilage ends with the onset of endochondral
      bone formation which has inferior mechanical properties. In this review, current
      strategies for inhibition of chondrogenic hypertrophy are comprehensively
      summarized; the impact of cell source options is discussed; and potential
      mechanisms underlying these strategies are also categorized. This paper aims to
      provide guidelines for the prevention of hypertrophy in the regeneration of
      cartilage tissue. This knowledge may also facilitate the retardation of
      osteophytes in the treatment of osteoarthritis.

PMID- 26000338
TI  - Life cycle analysis on fossil energy ratio of algal biodiesel: effects of
      nitrogen deficiency and oil extraction technology.
AB  - Life cycle assessment (LCA) has been widely used to analyze various pathways of
      biofuel preparation from "cradle to grave." Effects of nitrogen supply for algae
      cultivation and technology of algal oil extraction on life cycle fossil energy
      ratio of biodiesel are assessed in this study. Life cycle fossil energy ratio of
      Chlorella vulgaris based biodiesel is improved by growing algae under nitrogen
      limited conditions, while the life cycle fossil energy ratio of biodiesel
      production from Phaeodactylum tricornutum grown with nitrogen deprivation
      decreases. Compared to extraction of oil from dried algae, extraction of lipid
      from wet algae with subcritical cosolvents achieves a 43.83% improvement in
      fossil energy ratio of algal biodiesel when oilcake drying is not considered. The
      outcome for sensitivity analysis indicates that the algal oil conversion rate and
      energy content of algae are found to have the greatest effects on the LCA results
      of algal biodiesel production, followed by utilization ratio of algal residue,
      energy demand for algae drying, capacity of water mixing, and productivity of
      algae. 

PMID- 26000339
TI  - Subtype-dependent Morphological and Functional Degeneration of Retinal Ganglion
      Cells in Mouse Models of Experimental Glaucoma.
AB  - In this short review, Puyang and her colleagues compared the results from three
      laboratories on the dendritic and functional degeneration of retinal ganglion
      cells (RGCs) in mouse models of experimental glaucoma [1-4]. Acute or chronic
      ocular hypertension was induced in mice, and different techniques were applied to
      identify RGC types. The dendritic alternations of RGCs were examined following
      the induction of ocular hypertension, and their light response properties were
      characterized by the multi-electrode array (MEA) recording. These studies support
      the notion that the morphological and functional degeneration of RGCs are subtype
      dependent in experimental glaucoma.

PMID- 26000340
TI  - Effects of Physical Exercise on Executive Functions: Going beyond Simply Moving
      to Moving with Thought.
AB  - Studies of the cognitive benefits of physical activity need to move beyond simple
      aerobic activities that require little thought (treadmill running, riding a
      stationary bicycle, or rapid walking) and resistance training. Many studies have
      looked at this in older adults, and the evidence points strongly to those
      activities having little or no cognitive benefit, certainly little or no
      improvement to the executive functions that depend on prefrontal cortex. There is
      encouraging evidence for other types of physical activity improving executive
      functions; however they have received far less study.

PMID- 26000341
TI  - Ductile thermoset polymers via controlling network flexibility.
AB  - We report the design and synthesis of a polymer structure from a cross-linkable
      epoxy-ionic liquid system which behaves like a hard and brittle epoxy thermoset,
      perfectly ductile thermoplastic and an elastomer, all depending on controllable
      network compositions. 

PMID- 26000342
TI  - Non-monotonic cellular responses to heterogeneity in talin protein expression
      level.
AB  - Talin is a key cell-matrix adhesion component with a central role in regulating
      adhesion complex maturation, and thereby various cellular properties including
      adhesion and migration. However, knockdown studies have produced inconsistent
      findings regarding the functional influence of talin in these processes. Such
      discrepancies may reflect non-monotonic responses to talin expression-level
      variation that are not detectable via canonical "binary" comparisons of
      aggregated control versus knockdown cell populations. Here, we deployed an
      "analogue" approach to map talin influence across a continuous expression-level
      spectrum, which we extended with sub-maximal RNAi-mediated talin depletion.
      Applying correlative imaging to link live cell and fixed immunofluorescence data
      on a single cell basis, we related per cell talin levels to per cell measures
      quantitatively defining an array of cellular properties. This revealed both
      linear and non-linear correspondences between talin expression and cellular
      properties, including non-monotonic influences over cell shape, adhesion complex
      F-actin association and adhesion localization. Furthermore, we demonstrate talin
      level-dependent changes in networks of correlations among adhesion/migration
      properties, particularly in relation to cell migration speed. Importantly, these
      correlation networks were strongly affected by talin expression heterogeneity
      within the natural range, implying that this endogenous variation has a broad,
      quantitatively detectable influence. Overall, we present an accessible analogue
      method that reveals complex dependencies on talin expression-level, thereby
      establishing a framework for considering non-linear and non-monotonic effects of
      protein expression-level heterogeneity in cellular systems. 

PMID- 26000343
TI  - Recent developments in electrochemistry at the interface between two immiscible
      electrolyte solutions for ion sensing.
AB  - Ion transfer at the interface between two immiscible electrolyte solutions allows
      the non-redox electrochemical detection of ions ranging from protons to
      macromolecules such as proteins. New electrochemical methods and analytical
      procedures have been developed in recent years to achieve limits of detection of
      from MUM down to tens of pM for ion sensing in biomedical diagnostics and in
      environmental monitoring. This article reviews the developments of the period
      2010-2015. 

PMID- 26000344
TI  - Label-free monitoring of plasmonic catalysis on the nanoscale.
AB  - Plasmonics is the description of specific light matter interactions of metallic
      structures. In general the size of such structures is well in the nanometer
      regime and also determines such specific characteristics as color, field
      confinement etc. Plasmon-induced hot electrons play a vital role in so-called
      plasmonic catalysis, a field that has recently attracted attention as a new
      reaction platform. Current reports introduce such nanoscale catalysis as an
      effective approach to concentrate the energy of visible light and direct it to
      adsorbed molecules, thereby increasing the chemical reaction rate, and
      controlling the reaction selectivity. In this review, we present various plasmon
      catalyzed reactions specifically monitored with Raman spectroscopy, namely
      surface-enhanced Raman scattering (SERS), remote SERS (Re-SERS) and tip-enhanced
      Raman scattering (TERS). These techniques utilize the signal enhancing effect of
      the metal nanoparticles. However, at the same time they can be used to control
      the actual reactivity. In the first part, the mechanism of plasmonic catalysis is
      introduced. Then it is shown how catalytic reactions can be spectroscopically
      investigated far beyond the diffraction limit using TERS. Finally, the
      sensitivity of the methods is discussed. 

PMID- 26000345
TI  - A non-PCR SPR platform using RNase H to detect MicroRNA 29a-3p from throat swabs
      of human subjects with influenza A virus H1N1 infection.
AB  - As in all RNA viruses, influenza viruses change and mutate constantly because
      their RNA polymerase has no proofreading ability. This poses a serious threat to
      public health nowadays. In addition, traditional pathogen-based detection methods
      may not be able to report an infection from an unknown type or a subtype of virus
      if its nucleotide sequence is not known. Because of these factors, targeting host
      microRNA signatures may be an alternative to classify infections and distinguish
      types of pathogens as microRNAs are produced in humans shortly after infection.
      Although this approach is in its infant stage, there is an urgent need to develop
      a rapid reporter assay for microRNA for disease control and prevention. As a
      proof of concept, we report herein for the first time a non-PCR MARS (MicroRNA
      RNase-SPR) assay to detect the microRNA miR-29a-3p from human subjects infected
      with influenza virus H1N1 by surface plasmon resonance (SPR). In our MARS assay,
      RNase H is employed to specifically hydrolyze the RNA probes immobilized on the
      gold surface where they hybridize with its cognate target cDNAs miR-29a-3p, where
      it was formed from reverse transcription with mature miR-29a-3p specific stem
      looped primers. After the digestion of the RNA probe by RNase H, the intact cDNA
      was released from the RNA-DNA hybrid and bound to a new RNA probe for another
      enzymatic reaction cycle to amplify signals. With assay optimization, the
      detection limit of our MARS assay for miR-29a-3p was found to be 1 nM, and this
      new assay could be completed within 1 hour without thermal cycling. This non-PCR
      assay with high selectivity for mature microRNA provides a new platform for rapid
      disease diagnosis, quarantine and disease control. 

PMID- 26000347
TI  - Response.

PMID- 26000346
TI  - Cold shock induces apoptosis of dorsal root ganglion neurons plated on infrared
      windows.
AB  - The chemical status of live sensory neurons is accessible with infrared
      microspectroscopy of appropriately prepared cells. In this paper, individual
      dorsal root ganglion (DRG) neurons have been prepared with two different
      protocols, and plated on glass cover slips, BaF2 and CaF2 substrates. The first
      protocol exposes the intact DRGs to 4  degrees C for between 20-30 minutes before
      dissociating individual neurons and plating 2 hours later. The second protocol
      maintains the neurons at 23  degrees C for the entire duration of the sample
      preparation. The visual appearance of the neurons is similar. The viability was
      assessed by means of trypan blue exclusion method to determine the viability of
      the neurons. The neurons prepared under the first protocol (cold exposure) and
      plated on BaF2 reveal a distinct chemical signature and chemical distribution
      that is different from the other sample preparations described in the paper.
      Importantly, results for other sample preparation methods, using various
      substrates and temperature protocols, when compared across the overlapping
      spectral bandwidth, present normal chemical distribution within the neurons. The
      unusual chemically specific spatial variation is dominated by a lack of protein
      and carbohydrates in the center of the neurons and signatures of unraveling DNA
      are detected. We suggest that cold shock leads to apoptosis of DRGs, followed by
      osmotic stress originating from ion gradients across the cell membrane leading to
      cell lysis. 

PMID- 26000348
TI  - [Stercoral perforation of the colon: case report and literature review].
AB  - INTRODUCTION: Colon perforation has several causes, including stercoral
      perforation of the colon, which was first described in 1894. Currently, reported
      cases are fewer than 100. CASE REPORT: Male patient of 67 years old, treated at
      Huichapan General Hospital, Hidalgo, Mexico, with abdominal pain, bloating and no
      bowel movements. He referred being constipated for the last ten years. Imaging
      revealed an extremely dilated sigmoid colon with fecal matter as well as free gas
      in the peritoneal cavity. The suspicion of stercoral colonic perforation is
      established. Exploratory laparotomy was performed immediately, finding a
      perforation and a hard scybalum protruding in the ascending colon. Colectomy,
      ileostomy and Hartmann's pouch are performed. After surgery, the condition of the
      patient worsened and progressed to septic shock and respiratory failure. The
      patient died four hours after surgery, with the diagnosis of organ failure due to
      sepsis. LITERATURE REVIEW: Stercoral perforation accounts for 3.2% of all colon
      perforations and is caused by a rupture of the intestinal wall through direct
      pressure of a fecaloma on the colon. It occurs especially in patients older than
      70 years with severe chronic constipation, weakened and/or are hospitalized with
      multiple medications and immobilized. CONCLUSIONS: Stercoral perforation of the
      colon is a rare cause of bowel perforation, which should be suspected in patients
      with a history of chronic constipation, acute abdominal pain, bloating and
      sepsis, in order to intervene in a timely fashion.

PMID- 26000349
TI  - Response.

PMID- 26000350
TI  - Special issue: the 15th Taishotoyama International Symposium on Gastroenterology
      (2). Forward.

PMID- 26000351
TI  - Special issue: the 15th Taishotoyama International Symposium on Gastroenterology
      (2). Preface.

PMID- 26000352
TI  - Response.

PMID- 26000353
TI  - Relocation: Out of place.

PMID- 26000354
TI  - A management algorithm for acute heart failure in pregnancy. The Hannover
      experience.

PMID- 26000355
TI  - Detecting and managing cardiovascular disease  during pregnancy in Africa.

PMID- 26000356
TI  - 'Social freezing' of women's eggs.

PMID- 26000357
TI  - Crown-to-implant ratio: what is the latest?

PMID- 26000359
TI  - Stage 3 EHR meaningful use proposals include eight core goals.

PMID- 26000358
TI  - Reply letter to editor. Acute effects of continuous positive airway pressure on
      pulse pressure in CHF.

PMID- 26000360
TI  - Proposed: eight Stage 3 meaningful use objectives and their measures.

PMID- 26000361
TI  - ICD-10 is finally on the horizon.

PMID- 26000362
TI  - Medication reconciliation: make it somebody's job.

PMID- 26000363
TI  - Successful sepsis program leads to national award.

PMID- 26000364
TI  - ICU program gets patients moving sooner.

PMID- 26000365
TI  - The role of nanotechnology in induced pluripotent and embryonic stem cells
      research.
AB  - This paper reviews the recent studies on development of nanotechnology in the
      field of induced pluripotent and embryonic stem cells. Stem cell therapy is a
      promising therapy that can improve the quality of life for patients with
      refractory diseases. However, this option is limited by the scarcity of tissues,
      ethical problem, and tumorigenicity. Nanotechnology is another promising therapy
      that can be used to mimic the extracellular matrix, label the implanted cells,
      and also can be applied in the tissue engineering. In this review, we briefly
      introduce implementation of nanotechnology in induced pluripotent and embryonic
      stem cells research. Finally, the potential application of nanotechnology in
      tissue engineering and regenerative medicine is also discussed.

PMID- 26000366
TI  - Targeted drug delivery systems for pancreatic cancer.
AB  - Pancreatic cancer is usually diagnosed at the advanced stages, responds poorly to
      the available chemotherapeutics and constitutes the major factor for high
      mortality rate. Selective delivery of therapeutics to their cellular targets,
      without side effects is the foremost objective of the current investigations for
      effective treatment of pancreatic cancer. The development of the drugs which can
      selectively target pancreatic cancer along with carriers that can deliver drugs
      specifically to the rapidly dividing cells is considered as magic bullet for the
      efficient treatment of this fatal disease. This review describes various factors
      hampering the efficacy of drug targeting to pancreatic cancer including stromal
      fortress, hypocascularity, hyaluronan and interstitial fluid pressure, and
      exploration of various cellular targets for the site specific drug delivery. An
      account of burgeoning applications of novel drug delivery systems including
      nanoparticles, liposomes, quantum dots, micelles and drug conjugates in the
      management of pancreatic cancer is also provided. Additionally, potential of
      target based therapeutic agents and nanomedicines in clinical trials for the
      pancreatic cancer therapy are highlighted.

PMID- 26000367
TI  - Nanocarriers in gene therapy: a review.
AB  - With its rapid development in the past few decades, gene therapy has shown
      potential for use as a standard clinical intervention for the treatment of
      several conditions, including cancers, infectious diseases, cardiovascular
      disorders, inner ear disorders, dermatological, ophthalmologic, and neurological
      pathologies. Current gene therapy is not limited to the delivery of DNA only.
      Other therapeutic nucleic acid materials such as small interfering RNA, antisense
      oligonucleotides, or microRNA have also been included into the protocols of gene
      therapy. The correct choice of vector is a key factor in the success of gene
      therapy, where both viral and non-viral vectors are commonly used. Viral vectors
      are associated with some severe side effects (e.g., immunologenicity and
      carcinogenicity). They show poor target cell specificity, are unable to transfer
      large-sized genes, and are costly. Therefore, non-viral vectors, especially
      nanocarriers, have become a realistic alternative to viral vectors for achieving
      better efficacy in gene therapy. Different types of nanocarriers such as
      liposomes, metallic and polymeric nanoparticles, dendrimers, gelatins, and
      quantum dots/rods have been developed, and each shows distinct characteristics.
      Nevertheless, a variety of new challenges should be properly addressed for
      ensuring the success of nanocarriers in clinical applications. In this review
      article, we first discuss the advances and applications of nanocarriers in gene
      therapy, and then describe the drawbacks and existing challenges of the emerging
      gene delivery methods based on the use of nanomaterials.

PMID- 26000368
TI  - Electrospun nanofibrous mats: from vascular repair to osteointegration.
AB  - Electrospinning is a versatile technique for generating a mat of continuous
      fibers with diameters from a few nanometers to several micrometers. The diversity
      of electrospinnable materials, and the unique features associated with
      electrospun fibers make this technique and its resultant structures attractive
      for applications in the biomedical field. This article presents an overview of
      this technique focusing on its application for tissue engineering. In particular,
      the advantages and disadvantages of using an electrospinning mat for biomedical
      applications are discussed. It reviews the different available electrospinning
      configurations, detailing how the different process variables and material types
      determine the obtained fibers characteristics. Then a description of how
      nanofiber based scaffolds offer great promise in the regeneration or function
      restoration of damaged or diseased bones, muscles or nervous tissue is reported.
      Different methods for incorporating active agents on nanofibers and controlling
      their release mechanisms are also reviewed. The review concludes with some
      personal perspectives on the future work to be done in order to include
      electrospinning technique in the industrial development of biomedical materials.

PMID- 26000369
TI  - Acrylic bone cements: the role of nanotechnology in improving osteointegration
      and tunable mechanical properties.
AB  - Nanotechnology is an extremely powerful emerging technology, which is expected to
      have a substantial impact on biomedical technology, especially in tissue
      engineering and drug delivery. The use of nanocompounds and nanoparticles in the
      synthesis of improved bone cements to be applied in vertebroplasty/kyphoplasty
      and arthroplasty, is of great interest due to the increasing incidence of
      osteoporosis and osteoarthritis. This review reports new advances in the
      development of acrylic bone cements, using different radio-opalescent
      nanomaterials taking into consideration their influence on the mechanical
      behavior and biocompatibility of the resulting acrylic bone cement. Furthermore,
      other non-radiopaque nanoparticles capable of mechanically reinforcing the bone
      cement as well as induce osteointegration, are also reviewed. Additionally,
      nanoparticles used to improve the controlled release of antibiotics contained in
      acrylic bone cements are briefly described.

PMID- 26000370
TI  - Anti-cancer activity of bromelain nanoparticles by oral administration.
AB  - Oral administration of anti-cancer drugs is an effective alternative to improve
      their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an
      effective anti-cancer phyto-therapeutic agent, however, its activity is reduced
      upon oral administration. In addressing the issue, BL was encapsulated in
      Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further,
      the NPs were coated with Eudragit L30D polymer to introduce stability against the
      gastric acidic conditions. The resultant coated NPs were characterized for BL
      entrapment, proteolytic activity and mean particle size. The stability and
      release pattern of NPs were evaluated under simulated gastrointestinal tract
      (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of
      diverse origin have shown significant dose advantage (-7-10 folds) with NPs in
      reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF
      7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as
      compared to free BL. Altered expression of marker proteins associated with
      apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti
      carcinogenic potential of formulated NPs. Oral administration of NPs reduced the
      tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also
      increased their life-span (160.0 +/- 5.8%) when compared with free BL (24 +/-
      3.2%). The generation of reactive oxygen species, induction of apoptosis and
      impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed
      the suitability of Eudragit coated BL-NPs as a promising candidate for oral
      chemotherapy.

PMID- 26000371
TI  - Anti-tumor immune response of folate-conjugated chitosan nanoparticles containing
      the IP-10 gene in mice with hepatocellular carcinoma.
AB  - Immunotherapy is one of the most promising new therapies for hepatocellular
      carcinoma (HCC) in recent years. In this study, folate-conjugated chitosan
      nanoparticles (FA-CS-NPs) were loaded with mouse interferon-gamma-inducible
      protein-10 (IP-10) plasmid, which were used for immunotherapy in HCC. H22 tumor
      bearing mice were treated with FA-CS-NPs entrapped IP-10 plasmid and targeting
      efficiency was observed by optical imaging in vivo. Flow cytometry was used to
      measure the number of myeloid-derived suppressor cells (MDSCs) in the tumor and
      CD4+CD25+FoxP3+ T-regulatory cells (CD4+CD25+FoxP3+ Tregs) in the spleen. The
      enzyme-linked immunospot (ELISPOT) assay was used to quantify the number of
      interferon-gamma (IFN-gamma)-positive cells. IP-10 expression, tumor vessel
      density, cell proliferation and apoptosis were evaluated by immunohistochemistry.
      It was shown that FA-CS-NPs entrapped IP-10 plasmid displayed anti-tumor activity
      with inhibition of tumor growth and prolonging the survival time in H22 tumor
      bearing mice. Treatment of H22 tumor-bearing mice with FA-CS-NPs entrapped IP-10
      plasmid inhibited angiogenesis and promoted IP-10 expression and induced
      apoptosis in the tumor. FA-CS-NPs entrapped IP-10 plasmid-treated mice also had a
      lower proportion of Tregs in the spleen, a higher proportion of MDSCs in the
      tumor and higher number of IFN-gamma-positive cells in the spleen compared with
      the mice from the other experimental groups. These data suggested that the gene
      delivery system of folate-conjugated chitosan nanoparticle loaded with IP-10
      plasmid may be a promising strategy for immunotherapy of HCC.

PMID- 26000372
TI  - Complex effect of hydroxyapatite nanoparticles on the differentiation and
      functional activity of human pre-osteoclastic cells.
AB  - Nanosized hydroxyapatite (HA) is a promising material in clinical applications
      targeting the bone tissue. NanoHA is able to modulate bone cellular events, which
      accounts for its potential utility, but also raises safety concerns regarding the
      maintenance of the bone homeostasis. This work analyses the effects of HA
      nanoparticles (HAnp) on osteoclastic differentiation and activity, an issue that
      has been barely addressed. Rod-like HAnp, produced by a hydrothermal
      precipitation method, were tested on peripheral blood mononuclear cells (PBMC),
      which contains the CD14+ osteoclastic precursors, in unstimulated or
      osteoclastogenic-induced conditions. HAnp were added at three time-points during
      the osteoclastic differentiation pathway, and cell response was evaluated for
      osteoclastic related parameters. Results showed that HAnp modulated the
      differentiation and function of osteoclastic cells in a dose- and time-dependent
      manner. In addition, the effects were dependent on the stage of osteoclastic
      differentiation. In unstimulated PBMC, HAnp significantly increased
      osteoclastogenesis, leading to the formation of mature osteoclasts, as evident by
      the significant increase of TRAP activity, number of TRAP-positive multinucleated
      cells, osteoclastic gene expression and resorbing ability. However, in a
      population of mature osteoclasts (formed in osteoclastogenic-induced PBMC
      cultures), HAnp caused a dose-dependent decrease on the osteoclastic-related
      parameters. These results highlight the complex effects of HAnp in osteoclastic
      differentiation and activity, and suggest the possibility of HAnp to
      modulate/disrupt osteoclastic behavior, with eventual imbalances in the bone
      metabolism. This should be carefully considered in bone-related and other
      established and prospective biomedical applications of HAnp.

PMID- 26000373
TI  - Translocation and toxicity of docetaxel multi-walled carbon nanotube conjugates
      in mammalian breast cancer cells.
AB  - Multi-walled-carbon nanotubes (MWNTs) are widely explored as carriers for drug
      delivery due to their facile transport through cellular membranes and are
      reportedly found to be effective against cancer. In the present study, we have
      evaluated cellular uptake of Docetaxel (DTX) conjugated MWNTs from human breast
      cancer cells (MCF-7 and MDA-mb-231) and have provided primary results on
      cytotoxicity of the same. Efficient internalization of the drug conjugate (DTX
      MWNTs) inside the cell was corroborated with the help of confocal microscopy,
      transmission electron microscopy and flow cytometry. The comparison of
      cytotoxicity of the conjugate and DTX was done by MTT assay. Results of the study
      indicated increased efficacy of the conjugates over the drug in terms of their
      cytotoxicity. It was observed that such conjugation of drug to MWNTs can be
      explored as a strategy to improve therapeutic index of cytotoxic drugs such as
      DTX and thereby enriching cancer therapies of coming time.

PMID- 26000374
TI  - Long spacer arm-functionalized magnetic nanoparticle platform for enhanced
      chemiluminescent detection of hepatitis B virus.
AB  - A simple and cost-effective platform based on conjugating long spacer arms (LSA)
      onto magnetic nanoparticles (MNPs) was developed to enhance the chemiluminescent
      (CL) detection of pathogens. The modification method is both convenient and
      practical because it utilizes the commercially available macromolecule,
      carboxymethylated glucan (CMG), as the LSA. CMG-MNPS are designed to have low
      steric hindrance and high suspension properties, which allow for facile
      modification and hybridization reactions that enhance the CL sensitivity and
      detection. The infectious pathogen, hepatitis B virus (HBV) was selected for
      feasibility testing on this platform. The biotinylated amplicon of HBV, obtained
      by polymerase chain reaction (PCR), was hybridized to DNA probes functionalized
      on CMG-MNPs. The magnetic complexes were then incubated with streptavidin
      alkaline phosphatase (SA-AP) to form linkages through biotin-streptavidin
      interactions. Finally, the magnetic complexes were mixed with 3-(2'
      spiroadamantyl)-4-methoxy-4-(3"-phosphoryoxy)-phenyl-1,2-dioxetane (AMPPD) to
      generate CL signals that were proportional to the concentration of the HBV
      target. The detection of HBV with CMG-MNPs was more sensitive than that with the
      conventional carboxylated MNPs (CMNPs, succinic anhydride-modified MNPs). When
      optimized, the novel method showed high specificity and a detection limit of 0.5
      pM. This new platform shows promise for the early clinical diagnosis of
      infectious diseases.

PMID- 26000375
TI  - Multifunctional layered gadolinium hydroxide nanoplates for ultrahigh field
      magnetic resonance imaging, computed tomography and fluorescence bioimaging.
AB  - The commonly used clinical magnetic resonance imaging (MRI) contrast agents are
      generally suitable for MR systems with a magnetic field less than 3.0 T. However,
      these agents show low contrast efficacy for MR systems with ultrahigh fields >=
      7.0 T, which is the direction that next-generation MRI scanners are heading. A
      new contrast agent consisting of layered gadolinium hydroxide nanoplates doped
      with Ce and Tb (LGdH:Ce,Tb NPs) is presented herein. This material exhibits
      excellent negative (T2) contrast agent efficacy for 7.0 T MRI with a high r2/r1
      ratio of 48.80, whereas it exhibits a lower r2/r1 ratio of 30.60 for 3.0 T MRI.
      Its performance as a T2 contrast agent in ultrahigh field MRI of subcutaneous
      liver tumor-bearing nude mice is investigated, demonstrating its ability to be
      used as a negative target T2 contrast agent to distinguish hepatic carcinoma from
      healthy tissues. Furthermore, the multifunctionality of the LGdH:Ce,Tb NPs as a
      contrast agent in X-ray computed tomography (CT) and fluorescence bioimaging is
      also presented, suggesting the possibility of integrating these imaging
      technologies for in-depth exploration of bioimaging.

PMID- 26000376
TI  - Fabrication of 2D and 3D constructs from reconstituted decellularized tissue
      extracellular matrices.
AB  - We demonstrated a novel process to reconstitute a decellularized extracellular
      matrix (Recon-ECM) of heart and liver tissue using a combination of mechanical
      homogenization and enzymatic digestion. Such Recon-ECM was used as a biomaterial
      to produce flat or micro-patterned 2D films after crosslinking using replica
      molding. The mechanical properties of the resulting films were tuned by changing
      the type of crosslinking reagents. We also demonstrated the fabrication of
      mechanically robust 3D scaffolds by freeze-drying of the Recon-ECM solution. The
      porosity of the 3D scaffold was controlled by changing the concentration of the
      Recon-ECM. HepG2 cells were used to investigate the potential substrate of these
      engineered 2D patterned and 3D porous structures. The cell attachment,
      proliferation, and urea synthesis were evaluated, and the results indicate that
      the scaffold generated from Recon-ECM provides a biologically friendly
      environment for cells to grow. This method provides a new way to use
      decellularized ECM as a source of biomaterial to produce novel scaffolds with
      better controlled micro- and nano-scale structures, tunable physicochemical
      properties with desired biological functions.

PMID- 26000377
TI  - Anti-tumor activity of verbascoside loaded gold nanoparticles.
AB  - Verbascoside (VB), a major bioactive constituent of the Tsoong herb, has
      attracted a great deal of attention due to its pharmacological properties. In
      this study, we demonstrated the inhibitory effect of VB-loaded gold nanoparticles
      (VB-Au) on the growth of K562 cells both in vitro and in vivo. We found that, in
      contrast with the same concentration of gold nanoparticles (Au) or VB, VB-Au
      significantly decreased the viability of K562 cells and promoted the apoptosis of
      tumor cells. A tumor implantation mouse model further showed that the intravenous
      injection of VB-Au effectively inhibited the growth and induced the apoptosis of
      tumor cells. In conclusion, our results collectively demonstrate that VB-Au
      nanoparticles provide an effective strategy to control tumor cell growth.

PMID- 26000378
TI  - Liposomes versus lipid nanoparticles: comparative study of lipid-based systems as
      oryzalin carriers for the treatment of leishmaniasis.
AB  - Main-stay in treatment of leishmaniasis relies on chemotherapy but none of the
      current drugs combines high activity and low toxicity at affordable costs.
      Dinitroanilines are a new class of drugs with proved in vitro antileishmanial
      activity. However the development of their pharmaceutical formulations has been
      compromised by low water solubility and low accumulation in diseased organs.
      These limitations can be overcome by incorporation in lipid-based
      nanoformulations such as liposomes and solid lipid nanoparticles. In previous
      work this strategy was already followed with the incorporation of a
      dinitroaniline, oryzalin, resulting in the improvement of the biodistribution
      profile. The present work aims at demonstrating the in vitro and in vivo
      therapeutic activity of these oryzalin nanoformulations, and establishing a
      systematic comparison of both systems. After oryzalin incorporation suitable
      physicochemical properties for parenteral administration were obtained.
      Nanoformulations revealed reduced cytotoxicity and haemolytic activity when
      compared with free-oryzalin, while retaining the in vitro intracellular activity.
      Therapeutic activity, assessed in a murine model of visceral leishmaniasis, was
      evaluated in terms of number of administrations, dose-response and influence of
      the lipid excipient. Results demonstrate the superiority of both oryzalin
      nanoformulations on the reduction of parasitic burden in liver and spleen as
      compared to the control group (84 to 91%) and similar to Glucantime. A strong
      reduction in ED50 values (3 to 65 fold) as compared to free-oryzalin was also
      obtained, depending on the organ and nanoformulation used. Both oryzalin
      nanoformulations are potential candidates as therapeutic agents against visceral
      leishmaniasis.

PMID- 26000379
TI  - Self-assembled hyaluronate/protamine polyelectrolyte nanoplexes: synthesis,
      stability, biocompatibility and potential use as peptide carriers.
AB  - This work investigates a new type of polyelectrolyte complex nanocarrier composed
      of hyaluronic acid (HA) and protamine (PROT). Small (approximately 60 nm) and
      negatively charged nanoparticles (NPs) with a polydispersity index of less than
      0.2 were obtained with properties that were dependent on the mixing ratio,
      concentration of polyelectrolytes and molecular weight of HA. Salmon calcitonin
      (sCT) was efficiently (up to 100%) associated with the NPs, and the drug loading
      (9.6-39% w/w) was notably high, possibly due to an interaction between HA and
      sCT. The NPs released -70-80% of the sCT after 24 hours, with the estimated total
      amount of released sCT depending on the amount of HA and PROT present in the NPs.
      The isoelectric point of the NPs was close to pH 2, and the negative surface
      charge was maintained above this pH. The HA/PROT nanoplexes protected the sCT
      from enzymatic degradation and showed low toxicity to intestinal epithelial
      cells, and thus may be a promising oral delivery system for peptides.

PMID- 26000380
TI  - Aptamer-functionalized nanoparticles for drug delivery.
AB  - Aptamers are artificial single-stranded DNA or RNA sequences, usually 20-60 bases
      long, that fold into secondary and tertiary structures, which enables their
      binding to a wide range of targets, including amino acids, drugs, proteins or
      even entire cells, with high affinity and specificity. Generally synthesized
      through an in vitro selection and amplification process known as the SELEX
      (systematic evolution of ligands by exponential enrichment), selected aptamers
      have dissociation constants ranging from nanomolar to picomolar level.
      Nanotechnology is the manipulation of matter on an atomic and molecular scale,
      generally in the 1-100 nm dimension range. The many unique physicochemical
      properties of nanoparticles include their ultra-small size, large surface area-to
      mass ratio, and high reactivity, making them different from bulk materials and
      overcoming some of the limitations found in traditional therapeutic and
      diagnostic agents. By combining both technologies, aptamer-conjugated
      nanoparticles offer new opportunities for applications in biomedicine, including
      early diagnosis and drug delivery. This review summarizes the recent developments
      in aptamer-mediated drug delivery for therapeutics based on aptamer conjugation
      with a variety of nanoparticles.

PMID- 26000381
TI  - The role of nanotechnology in gastrointestinal cancer.
AB  - The rising interest in the utilization of nanoparticles for diagnosis and
      treatment in all cancers including gastrointestinal cancer has increased research
      interest, and funding in the area of medical nanotechnology. Interesting outcomes
      of research studies on different applications are published every day, and it
      include approaches such as molecular targeting, photodynamic therapy, and
      magnetic localization. The discoveries being made by research teams and the
      hypothesized applications are thus far very promising. There are limitations that
      must be researched and overcome, but the increasing evidence for the use of
      nanoparticles in cancer treatment cannot be ignored. In this review, several
      recent techniques are discussed on the development of more effective and targeted
      cellular/molecular techniques in the diagnosis and treatment of gastrointestinal
      cancer.

PMID- 26000382
TI  - The role of exogenous neural stem cells transplantation in cerebral ischemic
      stroke.
AB  - To observe the effects of neural stem cells (NSCs) transplantation in rats'
      striatum and subventricular zone (SVZ) in rat models of focal cerebral ischemia
      and reperfusion. Hippocampus was extracted from fetal rats with 14 days of
      gestation. Suspension culture was used to isolate and culture the rat's NSCs. A
      cerebral ischemia and reperfusion rat's model was made on the left side of the
      brain through occlusion of the left middle cerebral artery. Neurological signs
      were assessed by Zea Longa's five-grade scale, with scores 1, 2, and 3 used to
      determine the successful establishment of the rat's model. The NSCs were
      stereotaxically injected into the left striatum 24 hours after the successful
      rat's model was built. Rats were then randomly divided into 5 groups, namely,
      normal group, sham operation group, ischemia group, PBS transplantation group,
      and NSCs transplantation group, each of which was observed on day 3, day 7, and
      day 14. The ischemia-related neurological deficits were assessed by using a 7
      point evaluation criterion. Forelimb injuries were evaluated in all rats using
      the foot-fault approach. Infarct size changes were observed through TTC staining
      and cell morphology and structure in the infarct region were investigated by
      Nissl staining. Apoptosis and apoptosis-positive cell counts were studied by
      Tunel assay. Expressions of double-labeling positive cells in the striatum and
      subventricular zone (SVZ) were observed by BrdU/NeuN and BrdU/GFAP fluorescent
      double-labeling method and the number of positive cells in the striatum and SVZ
      was counted. Results from the differently treated groups showed that right
      hemiplegia occurred in the ischemia group, PBS transplantation group, and NSCs
      transplantation group in varying degrees. Compared with the former two groups,
      there was least hemiplegia in the NSCs transplantation group. The TTC staining
      assay showed that rats in the NSCs transplantation group had smaller infarct
      volume than those from the PBS transplantation group. The Nissl dyeing showed
      that there was a large area of neuronal necrosis and apoptosis in the ischemia
      and PBS transplantation groups, and damage was mainly focused in the striatum.
      Degeneration and damage of nerve cells were significantly reduced in the NSCs
      transplantation group. The Tunel assay showed that the number of apoptosis
      positive cells in the NSCs transplantation group was less than that in the PBS
      transplantation group at each time point. Double immunofluorescent labeling
      showed that the proliferation of endogenous neural stem cells began at the third
      day, reaching the peak at the 7th day, and was significantly reduced at the 14th
      day in the SVZ. The number of BrdU/NeuN increased significantly in the NSCs
      transplantation group compared to that in the PBS transplantation group (P <
      0.05). The number of BrdU/GFAP decreased significantly in the NSCs
      transplantation group compared to that of PBS transplantation group (P < 0.05).
      The number of BrdU/GFAP-positive cells in the striatum was observed to be much
      more in the PBS transplantation group than in the NSCs transplantation group.
      Both neurological deficits and coordination capacity of rats with cerebral
      ischemia were significantly improved via transplantation of the neural stem
      cells. In conclusion, transplantation of neural stem cells can therefore possibly
      promote the differentiation of endogenous NSCs into neurons and reduce their
      differentiation towards glial cells. Transplantation of the neural stem cells may
      also change the ischemic microenvironment of striatum, possibly inhibiting the
      proliferation of glial cells.

PMID- 26000383
TI  - High efficiency intracellular transport of cationic peptide stearate for gene
      delivery in tumor cells and multipotent stem cells.
AB  - Identifying an optimal gene vector is critical for improving transfection
      efficiency in gene therapy. In this study, a novel, non-viral gene vector
      composed of a stearate cationic peptide, Cys-Arg-His-Lys-Arg-His-Lys-Arg-His-Lys
      Arg-His (CRHKRHKRHKRH), was engineered. The stearate cationic peptide (STR-Pep)
      could form micelles via its amphipathic properties at a concentration of 182
      MUg/mL, and condense plasmid DNA effectively above weight ratio of 1:1 to form
      nanosize complex nanoparticles. Cellular uptake experiments confirmed that STR
      Pep micelles and STR-Pep/plasmid DNA complex nanoparticles could pass through
      cell membranes rapidly, promote endosomal escape and release plasmid DNA from the
      complex nanoparticles successfully. Compared to Lipofectamine 2000, a commercial
      gene transfection vector, the engineered vector displayed higher transfection
      efficiency in certain cell types. Moreover, the STR-Pep gene delivery system was
      less cytotoxic than Lipofectamine 2000. In vivo anti-tumor activity was achieved
      by STR-Pep-mediated gene therapy using the plasmid DNA of pigment epithelium
      derived factor (pPEDF). STR-Pep also regulated gene expression in bone-marrow
      derived mesenchymal stem cells (MSCs), effectively inducing osteogenesis and
      neurogenesis. These results demonstrate that STR-Pep is a potential non-viral
      vector for in vitro and in vivo gene delivery.

PMID- 26000384
TI  - Targeted delivery of tanshinone IIA-conjugated mPEG-PLGA-PLL-cRGD nanoparticles
      to hepatocellular carcinoma.
AB  - Tanshinone IIA (TSIIA) is an active constituent of the traditional Chinese
      medicinal plant Salvia miltiorrhiza that is known to have anti-tumor properties.
      In order to increase the selectivity of TSIIA's anti-tumor activity, the current
      study evaluated the tumor-targeting efficacy of TSIIA incorporated into
      nanoparticles (NPs). TSIIA was loaded into mPEG-PLGA-PLL-cRGD (methoxy
      polyethylene glycol, polylactic-co-glycolic acid, poly-L-lysine, cyclic arginine
      glycine-aspartic acid) nanoparticles (TNPs) and used to treat hepatocellular
      carcinoma in vitro and in vivo. Our data demonstrate that TNPs were stable and
      had an even size distribution as well as an extended TSIIA releasing time, and
      improved tumor-targeting activity. As a novel drug carrier system, TNPs
      significantly inhibited the development of liver cancer both in vitro and in
      vivo, proving to be a novel promising targeted treatment for liver cancer.

PMID- 26000385
TI  - Galactoxyloglucan-modified nanocarriers of doxorubicin for improved tumor
      targeted drug delivery with minimal toxicity.
AB  - Doxorubicin (Dox) is commonly used to treat human malignancies, and the efficacy
      of Dox can be maximized by limiting toxicity when combined with nanoparticles.
      PST-Dox nanoparticles were prepared via conjugation of doxorubicin to
      galactoxyloglucan polysaccharide (PST001) isolated from Tamarindus indica (Ti),
      and by ionic gelation with tripolyphosphate (TPP). This formulation possessed
      superior therapeutic efficiency because of the small size and increased surface
      to-volume ratio. The PST-Dox nanoparticles exhibited a pH-responsive Dox release
      in the acidic pH of 4.5, favoring as high as 90% Dox release in a sustainable
      manner. PST-Dox was characterized and evaluated for its in vitro and in vivo
      anticancer effects. Surprisingly, this nanoparticle formulation retained the
      cytotoxic effects of PST001 even at lower concentrations. In vitro studies
      confirmed the selective cytotoxicity of PST-Dox in cancer cells through the
      induction of apoptosis. In vivo toxicity studies demonstrated a lower LD50 for
      Dox and a higher LD50 for the PST-Dox. Evaluation of the biochemical,
      hematological and histopathological parameters in mice supported the safety and
      efficacy of this formulation compared to Dox. Biodistribution data substantiated
      the tumor-specific delivery of these particles. Although prospective studies are
      warranted, in a complex disease such as cancer, cell-selective and pH-sensitive
      nanoparticle-based targeted drug delivery systems should be used as an effective
      choice over standard agents, such as doxorubicin.

PMID- 26000386
TI  - Copolymers of covalently crosslinked linear and branched polyethylenimines as
      efficient nucleic acid carriers.
AB  - The present study describes the formation of copolymers of linear and branched
      PEIs (25 kDa each). These polyethylenimines (bPEI and IPEI) were crosslinked with
      each other to obtain branched-linear (BL) PEI copolymers using epichlorohydrin as
      a crosslinker in two steps. First, IPEI was reacted with epichlorohydrin to form
      IPEI-chlorohydrin (CHL) and subsequently, bPEI was grafted onto CHL in basic
      medium by in situ generation of epoxy functionalities. The two PEIs were
      crosslinked by varying the weight ratio of bPEI while keeping the amount of IPEI
      fixed. The ratio of two PEIs (1:1, 2:1, 3:1, 4:1 and 5:1) and crosslinking
      percentage of epichlorohydrin (5, 10, 15 and 20%) appeared as the main parameters
      to have affected the transfection efficiency. The lead conjugate/DNA complex was
      tested for in vivo transgene expression in Balb/c mice and was found to show
      maximum expression in the spleen.

PMID- 26000387
TI  - Enhanced radiosensitization by the cationic liposome-encapsulated thymidine
      analogue BrdU through the increased intracellular BrdU-uptake on human melanoma
      as compared to anionic or nonionic liposomal or free BrdU.
AB  - The synthetic thymidine analogue, 5-bromo-2'-deoxy-uridine (BrdU) was
      encapsulated in cationic liposome composed of dipalmitoylphosphatidylcholine,
      cholesterol and stearylamine (molar ratio = 1/1/0.2; diameter = 120 nm), and the
      radiosensitization of cationic liposomal BrdU was assessed on human melanoma
      cells HMV-II, with comparing to anionic or nonionic liposomal BrdU and free-BrdU.
      HMV-II cells were pretreated by cationic liposomal BrdU or free-BrdU and then
      exposed to X-ray, followed by WST-8 assay to examine cell proliferation. The
      radiation-induced change of nuclei was defined with Hoechst33342 staining. The
      rates of thymidine replacement by BrdU and DNA double-strand breaks on HMV-II
      cells were determined with an anti-BrdU antibody and anti-53BP1 antibody,
      respectively. On 7th day after X-ray irradiation at 3 Gy, cell proliferation was
      suppressed more markedly in the administration of cationic liposomal BrdU than
      free-BrdU at equivalent BrdU doses. Giant polykaryocytes were observed in
      cationic liposomal BrdU-treated HMV-II cells. Radiosensitization was enhanced
      dose-dependently along with BrdU doses of 0.1-0.8 MUM in the order: cationic
      liposomal BrdU > anionic liposomal BrdU > nonionic liposomal BrdU (see symbol)
      free-BrdU. Similarly, the cationic liposomal BrdU augmented the rate of thymidine
      moiety replacement by BrdU and DNA double-strand breaks more appreciably than
      free-BrdU. Therefore, the cationic liposome-encapsulation of BrdU would be one of
      favorable drug deliveries for facilitating the X-ray therapy against cancer.

PMID- 26000388
TI  - Colloidal soft nanocarrier for transdermal delivery of dopamine agonist: ex vivo
      and in vivo evaluation.
AB  - Ropinirole, an antiparkinsoism dopamine agonist, is used to treat Restless Legs
      Syndrome. However, orally it undergoes degradation in gastrointestinal tract and
      extensive first pass metabolism, resulting in its poor and variable
      bioavailability of the commercially available oral tablets. In the present
      investigation, soft nanocarriers, viz., microemulsion of ropinirole with the
      globule size of 160.2 +/- 3.87 nm and zeta potential of -4.24 mV was explored for
      transdermal application. Transdermal drug delivery offers benefits such as
      sustained therapeutic plasma levels of drugs, avoidance of first pass effect, and
      improved patient compliance. In comparison to the hydrogel, the developed
      microemulsion enhanced the drug permeation across the rat skin and porcine ear
      skin by 3.5 and 2 folds, respectively. Further, the developed microemulsion
      antagonized the catalepsy in the haloperidol-induced catalepsy rat model by 10
      folds as compared to the marketed tablets. Additionally, in rotenone induced
      Parkinsonism rat model, the microemulsion showed improvement in the motor
      function by 76% whereas the oral tablet showed only 5% restoration of the normal
      function. Besides this, the developed formulation successfully restored the
      catalase and superoxide dismutase levels which were significantly reduced by
      rotenone administration. Overall, the in vivo studies suggested the potential of
      the developed transdermal microemulsion of Ropinirole as a viable alternative to
      marketed formulations.

PMID- 26000389
TI  - Toxicity of silver nanoparticles to human dermal fibroblasts on microRNA level.
AB  - This study investigates the role of microRNA (miRNA) in the toxicity of silver
      nanoparticles (SNPs) to human dermal fibroblasts (HDFs). First, 20 nm SNPs were
      synthesized, and the MTT assay of the influence of SNPs on HDF proliferation
      showed that cytotoxicity was not induced by 200 MUM after 1, 4 and 8 h.
      Proteomics and miRNA sequencing technologies were then utilized to analyze
      protein and miRNA expression profiles, and 25 proteins and 246 miRNAs were found
      differentially expressed in HDFs treated with 200 MUM SNPs. By integrating
      transcriptome, proteome and miRNA sequencing, 6 differentially expressed miRNAs
      were found regulated 3 target mRNA-protein pairs by inducing mRNA degradation and
      repressing protein translation, thus leading to differences in expression
      patterns. Bioinformatics analysis revealed that targeted mRNAs/proteins of SNP
      induced differentially expressed miRNAs involved in 57 biological pathways. Four
      pathways were affected by differentially expressed miRNA, target mRNAs and target
      proteins simultaneously, namely 'Regulation of actin cytoskeleton,' 'Signaling of
      hepatocyte growth factor receptor,' 'Insulin signaling' and 'MAPK signaling
      pathway.' The results indicated that SNPs might induce HDF toxicity by affecting
      the cytoskeleton, ATP synthesis and apoptosis. The bioinformatics results were
      verified through cytoskeleton observation, ATP content analysis and cell
      apoptosis assay. SNP-induced differentially expressed miRNAs regulated the
      expression of target genes and proteins, leading to HDF toxicity through the
      destruction of cytoskeleton, reduction of intracellular ATP content and induction
      of apoptosis.

PMID- 26000390
TI  - Development of aequorin-based mast cell nanosensor for rapid identification of
      botulinum neurotoxin type B.
AB  - An aequorin-based mast cell sensor was developed for rapid identification and
      detection of protein toxins. To monitor mast cell activation and to improve the
      sensitivity of detection, aequorin was stably expressed in the cells and used as
      an indicator of calcium flux and the stable cell line was created. The procedures
      for preparing cells were optimized to improve the quantum yield and sensitivity
      of detection. The cells sensitized with anti-DNP (dinitrophenyl) IgE were capable
      of detecting as little as 0.1 ng/mL DNP-BSA in less than 2 min. To demonstrate
      the utility of this mast cell sensor in detecting protein toxins, an IgE chimeric
      protein (p21-Fcepsilon) was created. This was achieved by fusing the Fc region of
      IgE antibody to a 21-amino acid peptide (p21) derived from residues 40-60 of
      synaptotagmin II (Syt II), the protein receptor of botulinum neurotoxin type B
      (BoNT/B). In addition, magnetic beads linked with anti-BoNT/B polyclonal antibody
      were prepared to capture BoNT/B molecules in solution to make targets multivalent
      and concentrated. The p21-Fcepsilon binds to FcsRI receptors on RBL (Rat
      basophilic leukemia) cells and can be cross-linked by BoNT/B captured by the
      magnetic beads. This led to cell activation and Ca2+ flux indicated by an
      increase of quantum yield. This assay can detect as little as 100 pM (15 ng/mL)
      BoNT/B in less than 1 hr, which included the initial sample preparation time.
      This study lays a foundation for detecting other protein toxins using mast cell
      sensors.

PMID- 26000391
TI  - Cancer cell uptake of polymer hydrogel nanotubes.
AB  - To gain deeper understanding of how the shape and size of particles influence
      their interaction with cells, the uptake process of polymer hydrogel nanotubes
      (PNTs) by cancer cells was characterized. The PNTs were composed of crosslinked
      poly(ethylene glycol) segments with a diameter of 300 nm and a polydispersed
      length in the range of 2 to 20 MUm. The uptake of PNTs into human cervical
      carcinoma epithelia (HeLa) cells cultured in vitro was monitored by confocal
      laser fluorescence microscopy and details of PNT entry into cells were revealed
      by a series of confocal Z-section images and time-lapsed video microscopy. It was
      found that PNTs initiating contact with the cell membrane through the tips of the
      tubes were readily taken up by the cells, whereas the uptake of tubes approaching
      the cell surface in parallel manner was very difficult. The length of the tubes
      did not appear to affect cellular uptake. In fact, it was found surprisingly that
      PNTs as long as > 10 MUm were internalized by these non-phagocytic cells. The
      rate of PNT uptake varied significantly and was probably influenced by the angle
      of attachment. Better understanding of the interaction between PNTs and cells may
      provide important insight in the use of PNTs as potential anticancer drug
      delivery vehicles.

PMID- 26000392
TI  - Dye-doped organosilicate nanoparticles as cell-preserving labels for
      photoacoustic signal generation.
AB  - Nanoparticle-assisted ultrasound generation by pulsed laser or photoacoustic (PA)
      techniques has been employed in the study of several tissues both in vivo and in
      vitro. Among the many applications of this technology, the detection of few cells
      in vitro is of particular interest. However, the toxicity induced by laser
      irradiation used for PA signal generation, whether in the absence or the presence
      of PA enhancers, within single isolated cells has not yet been investigated in
      detail. Herein, we report our studies of the cellular health of two different
      nanoparticle-labeled cell lines one hour after being subjected to a single laser
      pulse in vitro. We selected for this study an Hs936 skin epithelial melanoma cell
      line, which can be naturally detected photoacoustically, as well as a T47D human
      mammary breast gland epithelial cell line which has proven difficult to detect
      photoacoustically due to the absence of natural melanin. We have evaluated the
      amplitude of the PA signal derived from these two cell types, unlabeled and
      labeled with nanoparticles of two types (gold nanoparticles, AuNPs, or rhodamine
      6G-doped organosilicate nanoparticles, R6G-NPOs), and assessed their health one
      hour subsequent to laser treatment. The current work corroborates previous
      findings that, for unlabeled cells, Hs936 produces a detectable PA signal whereas
      the T47D line does not. Cells labeled with AuNPs or R6G-NPOs produced a
      detectable PA signal of similar amplitude for the two cell lines. A significant
      number of Hs936 cells (both unlabeled cells and those labeled with AuNPs)
      exhibited cell nuclei alterations, as revealed by DAPI staining conducted an hour
      after photo treatment. Remarkably, the T47D cells suffered damage only when
      labeled with AuNPs. A significant finding, the R6G-NPOs proved capable of non
      destructive PA signal generation in both cell types. Our findings advocate a
      transformational path forward for the use of dye-doped silicate nanoparticles in
      cell-compatible PA studies permitting the handling and culturing of cells
      subsequent to their photoacoustic analysis.

PMID- 26000393
TI  - Non-invasively evaluating therapeutic response of nanorod-mediated photothermal
      therapy on tumor angiogenesis.
AB  - Gold nanorod-mediated photothermal therapy has been widely explored for cancer
      treatment. However, timely evaluation of the therapeutic response is difficult as
      current diagnostic approaches are largely based on measurements of tumor volume.
      The present study developed a non-invasive imaging strategy to rapidly assess the
      efficacy of photothermal therapy in mice bearing human tumor xenografts. In this
      study, gold nanorods modified with carboxylated bovine serum albumin showed both
      anti-tumor and anti-angiogenesis effects under near-infrared laser irradiation.
      An alpha(v)beta3 integrin-targeted multi-modal nanoprobe, Dendrimer-arginine
      glycine-aspartic acid (Den-RGD), was designed and intravenously injected into
      mice bearing tumor xenografts at 24 h after photothermal therapy. Magnetic
      resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging
      demonstrated that the Den-RGD not only visualized the tumors with high target-to
      background ratio, but also showed the ability to evaluate the therapeutic
      response by monitoring the tumor neovasculature. Additionally, the target-to
      background ratio on MRI and NIRF imaging correlated with the microvessel density
      in the Den-RGD groups. Immunofluorescence staining confirmed the targeting
      specificity of Den-RGD to the neovasculature at the tumor periphery. This dual
      modal imaging method holds the promise of evaluating therapeutic efficacy in
      vivo. Nanomedicine provides a multi-functional platform for treatment of cancer
      and image-guided assessment of anti-cancer therapy.

PMID- 26000394
TI  - Dynamic modulation of fimbrial extension and FimH-mannose binding force on live
      bacteria under pH changes: a molecular atomic force microscopy analysis.
AB  - Mechanical and conformational properties of type 1 fimbriae were evaluated on
      live bacterial cells by Single Molecule Force Spectroscopy (SMFS) and Dynamic
      Force Spectroscopy (DFS) in buffered solutions whose pH varied from 3 to 9. We
      evidenced that both fimbrial extension and fimbrial binding force to mannosylated
      surface are modulated with changing the externally applied shear force and the
      solution pH. In particular, intertwined FimA-FimA and FimH-mannose interactions
      lead to a 5 to 25-fold decrease of the fimbrial unwinding for pulling rates
      larger than 10 MUm/s and for pH values outside the range 5 to 7. In this pH
      range, the FimH-mannose binding force is maximal with a magnitude of -150-200 pN
      and the fimbriae extension reaches 8 MUm. The enhancement of the FimH-mannose
      binding force at neutral pH, as evidenced from molecular AFM analyses, strongly
      correlates with an optimum in yeast agglutination detected at pH 5 to 7. The
      results reported in this work suggest that "catch bond effect" was negligible
      over the range of pulling rates tested, and both FimA-FimA and FimH-mannose
      interactions under given pH and external shear force conditions modify the
      ability of the bacteria to efficiently colonize host surfaces.

PMID- 26000395
TI  - The inhibitory effects of a monoclonal antibody targeting neuropilin-1 on
      adhesion of glioma cells to fibronectin.
AB  - We investigated the inhibitory effects of anti-Neuropilin-1 monoclonal antibody
      (NRP-1 MAb) on adhesion of glioma cells to Fibronectin (FN) and the associated
      mechanisms. The effects of NRP-1 MAb on adhesion of U251 glioma cells and
      formation of stress fibers were studied using adhesion assays and confocal
      fluorescence microscopy. After treatment of U251 glioma cells with NRP-1 MAb,
      changes of related proteins adhering to FN were detected by co
      immunoprecipitation and Western blot. Adhesion assays showed that NRP-1 MAb
      played an inhibitory role in adhesion of U251 glioma cells. Confocal fluorescence
      microscopy, co-immunoprecipitation and Western blot showed that NRP-1 MAb can
      inhibit the formation of stress fibers adhering to U251 cells. NRP-1 MAb can also
      affect the formation of Integrin alpha5beta1-NRP-1 complex, and also reduce the
      level of phosphorylation of FAK and p130cas. In conclusion, NRP-1 MAb has the
      inhibitory effects on adhesion of glioma cells to FN. This effect is related to
      the inhibition of NRP-1 MAb on the formation of Integrin alpha5beta1-NRP-1
      complex, which leads to the inhibition of FAK/p130cas signaling pathway.

PMID- 26000396
TI  - Nanoemulsion based concomitant delivery of curcumin and etoposide: impact on
      cross talk between prostate cancer cells and osteoblast during metastasis.
AB  - An attempt has been made to use curcumin (CUR) in combination with Etoposide
      (ETP) by encapsulating in nanoemulsion, as two tier approach i.e., to evaluate
      improvement in efficacy of ETP on prostate cancer cells (PC3 and DU145) and to
      assess their effect on cross-talk between osteoblast and tumor cells leading to
      metastatic cascade in bones. Nanoemulsion was developed and evaluated for size,
      charge, in-vitro drug release and anticancer activity, effect on cross talk
      between osteoblast and prostate cancer cells and pharmacokinetics in rats. The
      entrapment efficiency of both ETP and CUR in nanoemulsion was more than 98% while
      the globule size was less than 150 nm with zeta potential - 29.8 mV. The percent
      inhibition in case of ETP and ETP: CUR (1:3 w/w) was 55.92 +/- 1.2 and 41.13 +/-
      2.4% (at 5 MUM) respectively when tested in PC3 cells. DU-145 seemed to be less
      responsive in comparison to PC3 cells both in respect of ETP and their mixture
      (ETP+ CUR). Our data shows that CUR and ETP after encapsulation in nanoemulsion
      (F5) were effectively delivered intracellularly in PC3 cells and the cytotoxicity
      of F5 was enhanced by 1.5 fold as compared to ETP + CUR at 5 MUM concentration.
      It has also been observed that mice calvarial osteoblasts cultured and incubated
      with PC-3 and DU-145 cells conditioned media induces inhibition of osteoblast
      differentiation event. While this inhibition was significantly reversed by F5 at
      5 MUM concentration over other treated groups, the pharmacokinetic profile of
      both ETP and CUR was also significantly improved when administered in
      nanoemulsion.

PMID- 26000397
TI  - The effects of particle shape and size on T2 relaxation in magnetic resonance
      imaging.
AB  - Superparamagnetic iron oxide nanoparticles have recently been developed as T2
      contrast agents for magnetic resonance imaging. Here we report the dependence of
      the phase relaxivity, r2, on the particle shape. We show that the size dependence
      of the relaxivity for spherical particles can be generalized to spheroidal
      particles. In addition, we show that the saturation of relaxivity above a certain
      size observed in spherical particles does not occur in the spheroidal particles
      investigated.

PMID- 26000398
TI  - PH-sensitive self-assembled carboxymethyl chitosan-modified DNA/polyethylenimine
      complexes for efficient gene delivery.
AB  - In this study, DNA/polyethylenimine/carboxymethy chitosan ternary complexes
      (DPCs) were developed as a pH-sensitive gene delivery system via a layer-by-layer
      self-assembly technique. The DPCs assumed an obvious layered structure and showed
      good DNA-condensation ability. The result of a DNase I protection assay indicated
      that DPCs could effectively protect DNA from being degraded by nucleases.
      Compared with DNA/polyethylenimine binary complexes (DPs), DPCs showed better
      stability in plasma and lower cytotoxicity and acute toxicity due to
      carboxymethyl chitosan (CMCS) modification. The results of a pH-sensitive
      experiment confirmed that the outermost CMCS layer of the DPCs could peel off in
      an acidic environment (pH 6.5) due to the pH sensitivity of CMCS. In vitro
      transfection results showed that DPCs have good transfection ability under
      conditions that mimicked a tumor's pH environment, which also indicated that CMCS
      could detach from the DPCs in response to the acidic environment of tumor tissue.
      These results showed that CMCS modification could endow DPCs with good stability
      and low toxicity without inhibiting transfection efficiency. In conclusion, DPCs
      have the advantages of long circulation, good safety, pH sensitivity and ease of
      construction, which might provide a promising approach for efficient gene
      delivery.

PMID- 26000399
TI  - Local delivery of vascular endothelial growth factor via nanofiber matrix
      improves liver regeneration after extensive hepatectomy in rats.
AB  - Vascular endothelial growth factor (VEGF) is a potent regulator for liver
      regeneration following partial hepatectomy. However, intravenous delivery of VEGF
      has yielded limited success in promoting the regeneration of remnant liver. Here
      we report a new approach to locally deliver recombinant VEGF from an electrospun
      poly-epsilon-caprolactone nanofiber mesh and its effect on improving rat liver
      regeneration after 70% hepatectomy. After applying the VEGF-releasing nanofiber
      mesh to the remnant liver lobes following hepatectomy in rats, the fractions of
      proliferating hepatocytes increased markedly at 48 h and 72 h in comparison with
      the control group receiving nanofiber meshes without VEGF. The expression of
      endogenous VEGF in liver tissue was also higher in the VEGF-nanofiber group than
      those in the control group. These results demonstrate that biodegradable
      nanofiber meshes offer a convenient and effective approach for local and
      sustained delivery of VEGF to the remnant liver following partial hepatectomy.

PMID- 26000400
TI  - Cytotoxicity and cytokine release in rat hepatocytes, C3A cells and macrophages
      exposed to gold nanoparticles--effect of biological dispersion media or corona.
AB  - The study aim was to investigate how gold nanoparticles (NPs) of different sizes
      (20 and 100 nm) influence primary hepatocytes, the hepatocyte cell line C3A and
      macrophage cytokine responses when dispersed in lung or blood relevant fluids.
      Gold Au NPs induced cytotoxicity in primary hepatocytes at the highest dose of 66
      MUg/cm2, this effect was modified by the dispersant, the effect was greater with
      lung lining fluid (LLF). Release of interleukin (IL)-6, Monocyte chemoattractant
      protein-1 (MCP-1) and IL-1beta was enhanced by the Au NPs and the effects were
      influenced by the particle size and dispersant. In medium, the smallest particle
      size was most effective at inducing IL-6 release, while in LLF the largest
      particles were most effective at inducing IL-6 release. Both 20 nm and 100 nm
      particles enhanced MCP-1 and IL-1beta in the presence of LLF. The Au particles
      had no cytotoxic effects nor did they stimulate the release of cytokines in the
      C3A hepatoma cell line. The Au NPs had no significant impact on macrophage
      viability. Particles induced IL-6 and TNF-alpha release. LLF and serum reduced
      the IL-6 response while albumin enhanced the TNF-alpha response compared to
      medium dispersed Au NPs. The Au NPs did not impact on MCP-1 release, but this
      cytokine was enhanced by albumin and serum, while it was depressed by LLF. The
      macrophage responses were lower than those evoked in primary hepatocytes. In
      conclusion, when assessing the cytotoxic and pro-inflammatory responses induced
      by Au NPs, the response is influenced by the dispersant, with different
      dispersants having different effects in different cell types.

PMID- 26000401
TI  - On two South-West Atlantic Diastylis (Cumacea: Crustacea), D. obliquisulcata n:
      sp. and D. geocostae, with remarks on this speciose genus.
AB  - A new species, Diastylis obliquisulcata from eastern Patagonia, is fully
      described and illustrated based on specimens collected in shallow waters.
      Diastylis obliquisulcata shares with 14 other species of this genus an opercular
      maxilliped 3, a short telson and rudimentary exopods on pereopods 3 and 4 in the
      females. Diastylis obliquisulcata can be easily distinguished from all these
      species by the females having an oblique groove or sulcus on each side of the
      carapace. The taxonomic position of this group of species in the genus Diastylis
      is discussed. The adult male of Diastylis geocostae is described for the first
      time, the adult female briefly redescribed, and its distribution, up to now known
      from the type locality only (Cabo Frio, Rio de Janeiro State), is extended to off
      Rawson, Argentina. Within this species there are reported ontogenetic changes in
      the carapace ornamentation, in the chaetotaxy of the telson, and in the length
      ratio between the telson and the uropod peduncle.

PMID- 26000403
TI  - On the distribution and conservation of the South American lizard genus
      Tropidurus Wied-Neuwied, 1825 (Squamata: Tropiduridae).
AB  - This study describes and analyzes the distribution of the lizard genus Tropidurus
      based on an updated database and the current taxonomy. General distributional
      patterns and endemism are identified, the distributions of several species are
      expanded and previous failures in the determination of specific names are
      corrected. I provide distributional maps for all species currently assigned to
      Tropidurus including all occurrence records collected and critical comments on
      the patterns documented and conservation.

PMID- 26000402
TI  - Revision of the Histopona italica group (Araneae: Agelenidae), with the
      description of two new species.
AB  - During a large survey of agelenid spiders from different private and museum
      collections, a closer examination of material from all over Italy (including type
      material and fresh material) previously identified as Histopona italica Brignoli
      1977, disclosed two new species for science, both belonging to the italica group.
      Based on the results of the present work, we describe Histopona leonardoi sp. n.
      and H. fioni sp. n. and revise the distribution pattern of H. italica group in
      Italy and Switzerland. Drawings and photographs of relevant structures and a
      table summary of the diagnostic characters allowing a fast separation of the
      species are provided.

PMID- 26000404
TI  - Two new genera of tube-making spittlebugs (Hemiptera: Machaerotidae:
      Enderleiniini).
AB  - Two new monotypic spittlebug genera and their type species in the family
      Machaerotidae, subfamily Enderleiniinae, are described and illustrated:
      Labramachaerota korupa gen. & sp. n. (with type locality in Cameroon) and
      Kyphomachaerota maaia gen. & sp. n. (with type locality in Sarawak, Malaysia).

PMID- 26000405
TI  - Taxonomic revision of the genus Brounopsis Blair (Coleoptera: Cerambycidae:
      Cerambycinae) with description of four new species.
AB  - The longicorn beetle genus Brounopsis Blair, 1937, is revised. A diagnosis of
      Brounopsis and a key to all five species of the genus are given. One previously
      known species, B. hudsoni Blair, 1937, is redescribed, and four species described
      as new: B. concolora sp. nov., B. nigrifacta sp. nov., B. deitzi sp. nov. and B.
      gourlayi sp. nov. Dorsal views of each species are provided as photographs. The
      genus occurs exclusively in the South Island of New Zealand and is associated
      with Cassinia spp. (Asteraceae).

PMID- 26000406
TI  - Memoan ciceroi gen. et sp. nov., a remarkable new firefly genus and species from
      the Atlantic Rainforest (Coleoptera: Lampyridae).
AB  - A species of firefly discovered in a fragile and rapidly disappearing Atlantic
      Rainforest biome in Brazil does not fit into any of the existing subfamilies nor
      described generic categories in the Lampyridae and is described here as Memoan
      ciceroi gen. et sp. nov. and classed as Lampyridae Incertae sedis, as it exhibits
      features of both the Amydetinae and Lampyrinae. An overview of subfamily
      arrangements and relevant generic characters is given to support this action.
      Memoan gen. nov. can be distinguished by its alveolate pronotum and elytra;
      subserrate antennae, antenommeres II-IX compressed, antennal sockets obliquely
      inserted on tubercles; labial palp one-segmented and obconic, and by its
      conspicuous pleuroventral suture.

PMID- 26000407
TI  - A new species of Suezichthys (Teleostei: Perciformes: Labridae) from the south
      eastern Pacific, with a redefinition of the genus and a key to species.
AB  - A new species of the fish family Labridae, Suezichthys rosenblatti, is described
      from specimens collected at Isla San Felix, Isla Juan Fernandez and Isla San
      Ambrosio, off the coast of Chile. Suezichthys rosenblatti is distinct in having a
      combination of 11 dorsal fin soft rays and 11 anal fin soft rays. It falls in the
      group of species that has 11/2 scale rows above the lateral line and lack a scaly
      sheath at the base of the dorsal and anal fins (S. aylingi Russell, S.
      caudovittatus Russell, S. gracilis (Steindachner & Doderlein) and S. soelae
      Russell). Unlike other members of this group, S. rosenblatti has haemal arches on
      vertebrae 10-11 (versus haemal arch only on vertebra 10). The monotypic
      Nelabrichthys ornatus (Carmichael) is now included in the genus Suezichthys and a
      revised generic description and key to species of Suezichthys is provided. The
      occurrence of S. rosenblatti in the south-eastern Pacific and S. ornatus in the
      south-western Indian Ocean and south Atlantic Ocean represent major range
      extensions of the genus Suezichthys.

PMID- 26000408
TI  - Blamada rubripronota, a new genus and species of the tribe Saperdini (Coleoptera:
      Cerambycidae: Lamiinae) from Southeast Asia.
AB  - A new saperdine species belonging to a new genus, Blamada rubripronota gen. et
      sp. nov., is described from Laos, Vietnam and China. The genus differs from other
      genera of the tribe Saperdini in having the antennal scape bearing an expanded
      and ridged ring at apex, and second antennomere relatively longer (more than 1/4
      of scape in length) than that of other saperdine taxa.

PMID- 26000409
TI  - Key and bibliography of the genera of European Trichoptera larvae.
AB  - The paper provides a synoptic key to the genera of final instar European
      Trichoptera larvae. The most important characters are illustrated by colour
      photos, with arrows highlighting the diagnostic features. A short descriptive
      text gives additional information for each decision and guides the reader through
      the determination process.

PMID- 26000410
TI  - Review of the fish-parasitic genus Cymothoa Fabricius, 1793 (Isopoda,
      Cymothoidae, Crustacea) from the southwestern Indian Ocean, including a new
      species from South Africa.
AB  - The genus Cymothoa Fabricius, 1793 is revised for southwestern Indian Ocean
      waters. Cymothoa borbonica Schioedte & Meinert, 1884 and C. eremita Brunnich,
      1783 are redescribed. Cymothoa rotundifrons Haller, 1880, from Mauritius lacks
      type material and the host is unknown, therefore it is here relegated to nomen
      dubium. Cymothoa sodwana sp. nov., from Trachinotus botla (Carangidae), collected
      from the Kwazulu-Natal coast of South Africa, is described and is distinguished
      by the large, ovoid, hunched body with rugose dorsal surfaces; the anterolateral
      angles of pereonite 1 are narrow and rounded reaching half the length of the
      cephalon; the ischium of pereopod 7 has a large protrusion and pereonite 7 which
      laterally overlaps the pleon margins, extending posteriorly to the pleotelson.

PMID- 26000412
TI  - Iberian species of the subgenus Bunobus De Ley, Siddiqi & Bostrom, 1993
      (Nematoda, Rhabditida, Cephalobidae), with description of Pseudacrobeles
      (Bunobus) rotundilabiatus sp. n. and comments on the subgenus.
AB  - Two Iberian species of the subgenus Pseudacrobeles (Bunobus), one new and another
      known, collected from natural areas are described and illustrated, including
      morphometric and LM photographs. Pseudacrobeles (Bunobus) rotundilabiatus sp. n.
      is characterized by a body length of 624-805 MUm long in females and 670-714 MUm
      in males, lateral field with three incisures terminating gradually near the
      phasmid, lip region continuous with the adjacent body, subdorsal and subventral
      lips rounded, lateral lips reduced, stoma 13-17 MUm long, pharyngeal corpus 3.0
      4.3 times as long as isthmus, V = 63-74, spermatheca 22-62 MUm long, postvulval
      sac 1.0-2.0 times the body diameter in length, female tail conical elongated (59
      83 MUm, c = 9.7-11.6, c' = 4.5-6.8) ending in a lanceolate mucro slightly
      tuberculate proximally, male tail conical (38-40 MUm long, c = 10.1-16.8, c' =
      3.9), spicules 25 m long, and gubemaculum 14 m long. Pseudacrobeles (Bunobus)
      pseudolatus is re-described based on type specimens. In addition, an emended
      diagnosis is provided for the subgenus as well as an updated list of species, a
      compendium of their morphometrics and a key to their identification.

PMID- 26000411
TI  - Two novel genera and one new species of treefrog (Anura: Rhacophoridae) highlight
      cryptic diversity in the Western Ghats of India.
AB  - Amphibian diversity in the Western Ghats-Sri Lanka biodiversity hotspot is
      extremely high, especially for such a geographically restricted area. Frogs in
      particular dominate these assemblages, and the family Rhacophoridae is chief
      among these, with hundreds of endemic species. These taxa continue to be
      described at a rapid pace, and several groups have recently been found to
      represent unique evolutionary clades at the genus level. Here, we report DNA
      sequences, larval and breeding data for two species of rhacophorid treefrog
      (Polypedates bijui and a new, hitherto undescribed species). Remarkably, they
      represent unique, independent clades which form successive sister groups to the
      Pseudophilautus (Sri Lanka) + Raorchestes (India, China & Indochina) clades. We
      place these species into two new genera (Beddomixalus gen. nov. and Mercurana
      gen. nov.). Both of these genera exhibit a distinct reproductive mode among
      Rhacophoridae of peninsular India and Sri Lanka, with explosive breeding and
      semiterrestrial, unprotected, non-pigmented eggs oviposited in seasonal swamp
      pools, which hatch into exotrophic, free-living aquatic tadpoles. Relationships
      and representation of reproductive modes in sister taxa within the larger clade
      into which these novel genera are placed, is also discussed. These results
      suggest that more undescribed taxa may remain to be discovered in South Asia, and
      the crucial importance of conserving remaining viable habitats.

PMID- 26000413
TI  - Three new species of Rhyacophila (Trichoptera: Rhyacophilidae) from Taiwan and
      Nepal.
AB  - Three new species of the Rhyacophila scissa Group in the genus Rhyacophila
      (Trichoptera, Rhyacophilidae), i.e., Rhyacophila matanyii n. sp. from Taiwan
      (Republic of China), Rhyacophila steinmanni n. sp. and Rhyacophila kisszoltani n.
      sp. from Nepal are described and illustrated with drawings of the genitalia.

PMID- 26000414
TI  - New records of processid shrimps from the Indo-West and East Pacific (Crustacea:
      Decapoda).
AB  - New records are presented for the caridean shrimp family Processidae in Indo-West
      and East Pacific waters, based mainly on recently collected material. These
      records highlight that many processid species may be relatively widespread,
      although the distribution of some species remains imperfectly known. The colour
      pattern of several species is here documented for the first time, showing its
      potential use as an additional identification character. The available
      information on the ecology of the reported species is summarised.

PMID- 26000415
TI  - A new oviraptorid (Dinosauria: Theropoda) from the Upper Cretaceous of southern
      China.
AB  - This paper describes a new oviraptorid dinosaur taxon, Ganzhousaurus nankangensis
      gen. et sp. nov., based on a specimen collected from the Upper Cretaceous
      Nanxiong Formation of Nankang County, Ganzhou City, Jiangxi Province, southern
      China. This new taxon is distinguishable from other oviraptorids based on the
      following unique combination of primitive and derived features: relatively
      shallow dentary; absence of fossa or pneumatopore on lateral surface of dentary;
      weakly downturned anterior mandibular end; shallow depression immediately
      surrounding anterior margin of external mandibular fenestra; external mandibular
      fenestra subdivided by anterior process of surangular; dentary posteroventral
      process slightly twisted and positioned on mandibular ventrolateral surface;
      shallow longitudinal groove along medial surface of dentary posteroventral
      process; angular anterior process wider transversely than deep dorsoventrally;
      sharp groove along ventrolateral surface of angular anterior process; ventral
      border of external mandibular fenestra formed mainly by angular; ventral flange
      along distal half of metatarsal II; and arctometatarsal condition absent.
      Phylogenetic analysis places Ganzhousaurus nankangensis gen. et sp. nov. in the
      clade Oviraptoridae, together with Oviraptor, Citipati, Rinchenia and the unnamed
      Zamyn Khondt oviraptorid.

PMID- 26000416
TI  - The bush-cricket Isophya kraussii (Orthoptera: Phaneropteridae): bioacoustics,
      distribution and description of a new subspecies from Romania.
AB  - Isophya kraussii Brunner von Wattenwyl, 1878, one of the widest spread bush
      crickets within this genus, is confirmed to be present east of the Carpathian
      Mountains. Based on acoustic analysis and morphological characters, the
      populations from NE Romania are considered to belong to a different subspecies,
      I. kraussii moldavica ssp. n. A map with distribution of both subspecies is
      presented.

PMID- 26000417
TI  - A new genus of pine-feeding Cochylina from the western United States and northern
      Mexico (Lepidoptera: Tortricidae: Euliini).
AB  - Eupinivora, new genus, is described and illustrated from the montane regions of
      western United States (Nevada, Utah, Wyoming, Colorado, Arizona, New Mexico, and
      Texas) and Mexico (Nuevo Leon, Durango, and Estado de Mexico). As presently
      defined, the genus includes seven species: E. ponderosae, n. sp. (USA: Arizona)
      (type species); E angulicosta, n. sp. (Mexico: Nuevo Leon); E. albolineana, n.
      sp. (Mexico: Durango); E. thaumantias (Razowski, 1994), n. comb. (Mexico: Estado
      de Mexico); E. hamartopenis (Razowski, 1986), n. comb. (Mexico: Durango); E.
      unicolora, n. sp. (Mexico: Durango); and E. rufofascia, n. sp. (Mexico: Durango).
      The new genus is most closely related to Henricus Busck, 1943, from which it can
      be distinguished by the short upturned labial palpi, the presence of a variable
      cluster of long spine-like external setae from near the middle of the phallus in
      the male genitalia, the absence of cornuti in the vesica, the absence of the
      subgenital sex scales in the male, and a forewing pattern that in most of the
      included species is reminiscent of that of Argyrotaenia ponera Walsingham and its
      relatives. Four of the new species were reared from the cones of Pinus arizonica
      var. cooperi Blanco (Pinaceae) and one from Pinus ponderosa P. & C. Lawson; all
      of the species occur in habitats dominated by conifers at elevations between ca.
      1700 and 2750 m. Two specimens from New Mexico were collected in traps baited
      with a synthetic pheromone for the bud worm Choristoneura lambertiana (Busck,
      1915) (Archipini)-90% 92:8E:Z11-14AC, 10% 90:10E:Z11OH--which is consistent with
      that recorded for other Cochylina.

PMID- 26000418
TI  - Clathria (Clathria) Schmidt, 1862 from Brazil with description of a new species
      and a review of records (Poecilosclerida: Demospongiae: Porifera).
AB  - We report and describe material of Clathria (Clathria) (Poecilosclerida:
      Microcionina: Microcionidae) collected from the coast of Brazil: Clathria (C.)
      nicoleae sp. nov., Clathria (C.) calypso and Clathria (C.) prolifera. Clathria
      (C.) calypso is also redescribed. Specimens previously recorded from Brazil as
      Clathria (C.) prolifera were considered to fit better in the taxon Clathria
      (Wilsonella). The new species was compared with all other (twenty-five) Clathria
      (C.) species occurring in the Atlantic. The new species differs from the other
      species by overall morphology and presence of auxiliary tylostrongyle
      megascleres.

PMID- 26000419
TI  - The first species of the genus Caponina from Brazilian Amazonia (Araneae:
      Caponiidae).
AB  - The genus Caponina Simon, 1891 comprises eleven species of medium-sized, soil
      dwelling caponiids. Most members of Caponina have six eyes, but some have five,
      four, three or two eyes (Brignoli 1977, Platnick 1994). The genus is widespread
      in South and Central America (Platnick 2012). To date, only three species have
      been recorded from Brazil: Caponina alegre Platnick, 1994 from the state of Rio
      Grande do Sul, C. notabilis (Mello-Leitao, 1939) from the states of Parana and
      Rio Grande do Sul, and C. tijuca Platnick, 1994 from the state of Rio de Janeiro
      (Platnick 1994). In this paper we describe a new species from the state of Para,
      in Brazilian Amazonia. Caponina papamanga new species was collected during the
      "Butantan na Amazonia" project, founded by the Instituto Butantan. The
      phylogenetic relationships of C. papamanga could not be studied, but the greatly
      elongated embolus, the dorsal tubercle on the palpal femur (Figs. 7, 9) and the
      massive epigynal sclerotizations (Fig. 10) suggest that this species belongs to
      the monophyletic Andean group proposed by Platnick (1994: 7). All morphological
      observations and illustrations were made using a Leica MZ12 stereomicroscope with
      camera lucida. The epigynum was dissected and immersed in clove oil for
      visualization of internal structures following Levi (1965). Descriptions and
      measurements follow Platnick (1994). Measurements are given in millimeters.
      Scanning electron microscope (SEM) images were taken using a Jeol-JSM-5200 with
      attached SLR digital camera. The material examined was deposited in the
      collections of the Instituto Butantan, Sgo Paulo (IBSP, curator: D.M. Barros
      Battesti) and the Museu Paraense Emilio Goeldi, Belem (MPEG, curator: A.B.
      Bonaldo).

PMID- 26000420
TI  - A name for the glass catfish (Teleostei: Siluridae) revisited.

PMID- 26000421
TI  - Review of the genus Prosciara Frey (Diptera, Sciaridae) from China.
AB  - The genus Prosciara from China is reviewed and 36 species are recognized. Among
      them, 16 new species, P. oligotricha sp. nov., P. gyracantha sp. nov., P.
      hemicrypta sp. nov., P. angusta sp. nov., P. euryacantha sp. nov., P. ellipsoidea
      sp. nov., P. paucispina sp. nov., P. myriacantha sp. nov., P. columellata sp.
      nov., P. fossulata sp. nov., P. ternidigitata sp. nov., P. globoidea sp. nov., P.
      longispina sp. nov., P. extumida sp. nov., P. sinensis sp. nov. and P.
      tetracantha sp. nov. and 16 species, P. falcicula Vilkamaa & Hippa, P.
      latilingula Hippa & Vilkamaa, P. duplicidens Vilkamaa & Hippa, P. scopulifera
      Vilkamaa & Hippa, P. megachaeta Hippa & Vilkamaa, P. pentadactyla Hippa &
      Vilkamaa, P. pollex Hippa & Vilkamaa, P. crassidens Hippa & Vilkamaa, P. producta
      (Tuomikoski), P. exsecta Vilkamaa & Hippa, P. bisulcata Vilkamaa & Hippa, P.
      furcifera Hippa & Vilkamaa, P. latifurca Hippa & Vilkamaa, P. prolixa Vilkamaa &
      Hippa, P. triloba Hippa & Vilkamaa and P. decamera Hippa & Vilkamaa are reported
      for the first time from China. Manusciara Yang, Zhang & Yang, 1995 is recognized
      as a synonym of Prosciara, therefore, P. quadridigitata (Yang, Zhang & Yang,
      1995) is a new combination. In addition, geographical distribution of 36 Chinese
      species are provided, as well as a key to all these Chinese species. This study
      raises the number of the species of Chinese Prosciara from three to 36.

PMID- 26000422
TI  - Anthropogenic extinction of Pacific land snails: a case study of Rurutu, French
      Polynesia, with description of eight new species of endodontids (Pulmonata).
AB  - Faunistic surveys are fundamental in the conservation of land mollusks,
      particularly as a means of achieving accurate estimates of species richness and
      levels of extinction of endangered taxa. The family Endodontidae comprises one of
      the most diverse groups of indigenous land snails of Pacific Islands. Due to
      anthropogenic degradation of their habitats, most members of the family are now
      extinct or severely endangered. In Rurutu, French Polynesia, 11 species of
      Endodontidae were previously described (10 endemics), but only 1 is known to have
      been extant during the first half of the 20th Century. Extensive collections made
      in Rurutu in 2003 recovered only empty shells of these 11 species, as well as of
      an additional 8 endemic species of endodontids not known to previous
      investigators: Australdonta oheatora sp. nov., A. anneae sp. nov., A. sibleti sp.
      nov., A. florencei sp. nov., A. pakalolo sp. nov., A. teaae sp. nov., Minidonta
      boucheti sp. nov. and M. bieleri sp. nov. The radiation of endodontids in Rurutu
      was thus much larger than previously envisaged. However, we hypothesize that all
      species of the family are now extinct in the island.

PMID- 26000423
TI  - Non-invasive ancient DNA protocol for fluid-preserved specimens and phylogenetic
      systematics of the genus Orestias (Teleostei: Cyprinodontidae).
AB  - Specimens stored in museum collections represent a crucial source of
      morphological and genetic information, notably for taxonomically problematic
      groups and extinct taxa. Although fluid-preserved specimens of groups such as
      teleosts may constitute an almost infinite source of DNA, few ancient DNA
      protocols have been applied to such material. In this study, we describe a non
      invasive Guanidine-based (GuSCN) ancient DNA extraction protocol adapted to fluid
      preserved specimens that we use to re-assess the systematics of the genus
      Orestias (Cyprinodontidae: Teleostei). The latter regroups pupfishes endemic to
      the inter-Andean basin that have been considered as a 'species flock', and for
      which the morphology-based taxonomic delimitations have been hotly debated. We
      extracted DNA from the type specimens of Orestias kept at the Museum National
      d'Histoire Naturelle of Paris, France, including the extinct species O. cuvieri.
      We then built the first molecular (control region [CR] and rhodopsin [RH])
      phylogeny including historical and recently collected representatives of all the
      Orestias complexes as recognized by Parenti (1984a): agassizii, cuvieri, gilsoni
      and mulleri. Our ancient DNA extraction protocol was validated after PCR
      amplification through an approach based on fragment-by-fragment chimera
      detection. After optimization, we were able to amplify < 200 bp fragments from
      both mitochondrial and nuclear DNA (CR and RH, respectively) from probably
      formalin-fixed type specimens bathed entirely in the extraction fluid. Most of
      the individuals exhibited few modifications of their external structures after
      GuSCN bath. Our approach combining type material and 'fresh' specimens allowed us
      to taxonomically delineate four clades recovered from the well-resolved CR tree
      into four redefined complexes: agassizii (sensu stricto, i.e. excluding luteus
      like species), luteus, cuvieri and gilsoni. The mulleri complex is polyphyletic.
      Our phylogenetic analyses based on both mitochondrial and nuclear DNA revealed a
      main, deep dichotomy within the genus Orestias, separating the agassizii complex
      from a clade grouped under shallow dichotomies as (luteus, (cuvieri, gilsoni)).
      This 'deep and shallow' diversification pattern could fit within a scenario of
      ancient divergence between the agassizii complex and the rest of Orestias,
      followed by a recent diversification or adaptive radiation within each complex
      during the Pleistocene, in- and outside the Lake Titicaca. We could not recover
      the reciprocal monophyly of any of the 15 species or morphotypes that were
      considered in our analyses, possibly due to incomplete lineage sorting and/or
      hybridization events. As a consequence, our results starkly question the
      delineation of a series of diagnostic characters listed in the literature for
      Orestias. Although not included in our phylogenetic analysis, the syntype of O.
      jussiei could not be assigned to the agassizii complex as newly defined. The CR
      sequence of the extinct O. cuvieri was recovered within the cuvieri clade (same
      haplotype as one representative of O. pentlandii), so the mtDNA of the former
      species might still be represented in the wild.

PMID- 26000424
TI  - Systematics of the lace bug genus Cottothucha Drake and Poor (Insecta: Hemiptera:
      Heteroptera: Tingidae) with description of the first Australian species and its
      exaggerated nymph.
AB  - The lace bug genus Cottothucha is redescribed. Cottothucha kalathis from
      Australia is described as new to science. The fifth instar for C. kalathis is
      described and illustrated. Cottothucha minor and Cottothucha oceanae are
      redescribed. The male genitalia of these species are illustrated. The pronotal
      cyst is compared between the species and its evolution is discussed. The genus is
      maintained within the lace bug tribe Litadeini based on an enlarged tarsal
      segment.

PMID- 26000425
TI  - Checklist, taxonomy and distribution of the Rhagovelia Mayr, 1865 (Hemiptera:
      Heteroptera: Veliidae) of the Americas.
AB  - The genus Rhagovelia Mayr, 1865 is distributed worldwide, especially in the
      Tropics, and contains 184 species in the Americas, which are listed and included
      in complexes or grades, and in 18 species groups. Geographical distributions and
      altitudinal ranges are presented for each species. A new synonym is proposed, and
      some biogeographical aspects of the genus are analyzed, such as its distinct
      tropical distribution (97% of the known American species), and the narrow
      altitudinal ranges of the salina, tayloriella and cali groups. South America is
      determined to be the geographical area with the highest diversity of species (77%
      of the species richness of the Americas), and Brazil as the most biodiverse
      country.

PMID- 26000426
TI  - The second known specimen of Monodelphis unistriata (Wagner) (Mammalia:
      Didelphimorphia), with redescription of the species and phylogenetic analysis.
AB  - Very little information exists relevant to the species grouping and phylogenetic
      relationships of the opossum genus Monodelphis Burnett. Of the clearly distinct
      named species, the least information is available for M. unistriata (Wagner), one
      of the world's most poorly known species of mammals. Extant specimens consist of
      the Brazilian holotype of a skin now without a skull and dating from almost 200
      years ago, and a second specimen with skin and incomplete skull dating from over
      a hundred years ago and from Argentina. The most recent published notes on the
      holotype date from well over half a century ago and, all told, such notes, the
      earliest dating from 1842, add up to a highly fragmentary and contradictory
      picture. No observations whatsoever have ever been published for the second and
      more complete specimen. Also, no hypotheses have ever been made concerning the
      intrageneric affinities of M. unistriata and such affinities have also been
      obscure throughout the genus. Herein, we provide a detailed redescription of M.
      unistriata, the first published images of specimens, and the first account,
      beyond the previous few most vague and incomplete remarks, of the morphology of
      the skull. In an effort to ascertain the phylogenetic affinities of M.
      unistriata, we performed a combined molecular (cytochrome b) and nonmolecular
      (postcranial, cranial, integument, and karyotypic characters) parsimony analysis
      incorporating 27 species of didelphids, including 11 of Monodelphis. Our results
      strongly support the monophyly of Monodelphis, and place M. unistriata as sister
      group to M. iheringi, among the included species.

PMID- 26000427
TI  - Three new species of the Merodon nigritarsis group (Diptera: Syrphidae) from the
      Middle East.
AB  - Descriptions are given of three new species of Merodon Meigen (Diptera:
      Syrphidae) in the nigritarsis species group from the Middle East: Merodon
      angustus Vujic et Radenkovic n. sp., Merodon hakkariensis Vujic et Radenkovic n.
      sp. and Merodon quadraticus Vujic et Radenkovic n. sp. In addition, diagnostic
      characters are given for the nigritarsis group and distribution maps are
      presented for the new species and closely related taxa.

PMID- 26000428
TI  - Two new species of the genus Ficobracon van Achterberg and Weiblen (Hymenoptera:
      Braconidae) from China, expanding its host range.
AB  - Syconia of figs (Moraceae: Ficus spp.) harbour many wasp species, mostly
      belonging to several genera of chalcidoids (Hymenoptera: Chalcidoidea). In
      contrast, only two genera of Braconidae (Hymenoptera: Ichneumonoidea) with a few
      known species are found in syconia belonging to the subgenus Urostigma. The
      braconid fig wasps have an infrequent occurrence with low population density and
      are rarely encountered. Two new species, Ficobracon rhiknosus sp. nov. from figs
      of the subgenus Urostigma, and F. codonatus sp. nov. from figs of the subgenus
      Sycidium are described. Our previous experiments firmly support the suggestion
      that the Ficobracon species are parasitoids of non-pollinating chalcidoid fig
      wasps in the syconia.

PMID- 26000429
TI  - Diramus, a new genus of the leafhopper subfamily Evacanthinae (Hemiptera:
      Cicadellidae), with description of three new species from Thailand.
AB  - Diramus, gen. nov. (Hemiptera: Cicadellidae: Evacanthinae), and three new
      species, Diramus khaokus sp. nov., Diramus nigromaculatus sp. nov. and Diramus
      uncatus sp. nov., are described from Thailand. The differences between the new
      genus and the closely related genus Bundera Distant is discussed.

PMID- 26000430
TI  - The valid generic names for the fish species usually placed in Cyclocheilichthys
      (Pisces: Cyprinidae).
AB  - Cyclocheilichthys is the valid name for the genus that includes Barbus apogon
      Valenciennes. Cyclocheilichthys has precedence over Anematichthys, which is a
      simultaneous objective synonym. If C. enoplos is considered not to be congeneric
      with C. apogon, the valid name for a genus that includes it is Cyclocheilos.

PMID- 26000431
TI  - Comments on 'The valid generic names for the fish species usually placed in
      Cyclocheilichthys' (KOTTELAT 2013) and a correction of Pasco-viel et al. (2012).

PMID- 26000432
TI  - Macrobothriotaenia ficta (Cestoda: Proteocephalidea), a parasite of sunbeam snake
      (Xenopeltis unicolor): example of convergent evolution.
AB  - The poorly known proteocephalidean cestode Macrobothriotaenia ficta (Meggitt,
      1931) from the sunbeam snake Xenopeltis unicolor (Ophidia: Xenopeltidae) is
      redescribed on the basis of re-examination of its type specimens from Burma
      (Myanmar), and vouchers from Thailand and Vietnam. The peculiar morphology of the
      scolex, which is formed by four pedunculate lobe-bearing pincer-shaped suckers,
      is described for the first time using scanning electron microscopy. In scolex
      morphology, M. ficta closely resembles phyllobothriidean cestodes, parasites of
      elasmobranchs. However, this similarity does not reflect phylogenetic relatedness
      of these cestodes but instead presents an example of convergent morphological
      evolution of attachment organs of unrelated groups of cestodes that parasitize
      different groups of vertebrates. Besides scolex morphology, the genus is
      characterised by the possession of a very large cirrus-sac, which may reach up to
      the midline of proglottides, few testes (less than 60), vitelline follicles
      limited to the dorsal side of proglottides, a large vaginal sphincter, and eggs
      with a three-layered embryophore covered with rounded projections. Numerous
      errors in the diagnosis of M. ficta, which appeared in the literature as a result
      of uncritical compilation of data without examination of original material, are
      corrected. Multilocus phylogenetic analysis of nuclear ribosomal RNA genes ssr-
      and lsr-DNA and mitochondrial genes rrnL and cox1 place this species among other
      snake-parasitizing proteocephalideans of the genus Ophiotaenia. The convergent
      evolution of scolex morphology across distantly related taxa is discussed.

PMID- 26000433
TI  - Amietia angolensis and A. fuscigula (Anura: Pyxicephalidae) in southern Africa: a
      cold case reheated.
AB  - A study combining DNA sequences of the mitochondrial 16S rRNA gene, advertisement
      calls and morphology of some southern African river frogs confirms Amietia
      vandijki (Visser & Channing, 1997) as a good species. The form presently referred
      to as Amietia angolensis in southern Africa is shown to comprise two species:
      Amietia angolensis (Bocage, 1866) known from Angola, and Amietia quecketti
      (Boulenger, 1895) known from South Africa, Zimbabwe and Lesotho. Junior synonyms
      of A. quecketti include Rana theileri Mocquard, 1906 and Afrana dracomontana
      Channing, 1978. The form presently known as Amietia fuscigula is shown to consist
      of two distantly related taxa: Amietia fuscigula (Dumeril & Bibron, 1841) from
      the south-western Cape and an undescribed species that we here name Amietia
      poyntoni sp. nov. Channing & Baptista, known from the rest of South Africa and
      Namibia. These five species have large differences in 16S sequences, as well as
      differences in morphology and advertisement call. Call and molecular data are
      both diagnostic, while morphology shows some overlap between taxa. An extended
      study of the genus across Africa is in preparation.

PMID- 26000434
TI  - Revision of the genus Leopoldamys (Rodentia, Muridae) as inferred from
      morphological and molecular data, with a special emphasis on the species
      composition in continental Indochina.
AB  - A revision of the genus Leopoldamys is presented, and both the species
      composition and distribution in Indochina and Sundaic regions is reinvestigated.
      The phylogeny of the genus is recovered based on Cyt b, COI, and IRBP gene
      analyses. Five basal and 16 secondary monophyletic phylogenetic lineages were
      identified. A taxonomic reassessment of the continental and Sundaic populations
      is performed based on morphological verification of the genetically defined
      clades. Six clades were recovered in the phylogenetic analyses and correspond to
      morphologically defined species: L. revertens (distributed in lowlands of eastern
      and central Indochina), L. herberti (western and central Indochina, northward to
      northern Vietnam), L. edwardsi (China and northern Vietnam, northward of 21
      degrees N), L. milleti (endemic of Dalat Plateau, southern Vietnam), L. sabanus
      (Borneo), and L. vociferans (lowlands of the Malacca Peninsula, northward to
      southwestern Thailand). The absence of proper L. sabanus in continental Indochina
      is revealed. The substitute name for the species known from the majority of
      Indochina under the name of L. sabanus should be L. revertens. The name L.
      neilli, which has been ascribed to populations from Thailand and Vietnam, is a
      junior synonym of L. herberti. Two related but rather divergent clades are found
      in Sumatra and the Malacca Peninsula. Based on their considerable genetic
      distances, these forms should be regarded as separate species from the L. sabanus
      type-bearing populations of Borneo, or as the members of L. sabanus polytypic
      superspecies. The substitute name for the lineage-bearing taxon from Malacca
      should be L. vociferans. The continental populations of Leopoldamys can be
      distinguished from each other by external and cranial characters and may be
      subdivided into four species. Two of these species (L. revertens and L. milleti)
      are well distinguished by external and cranial morphology, whereas the other two
      species (L. herberti and L. edwardsi) may be treated as sibling species that are
      difficult to distinguish based on morphological characters.

PMID- 26000435
TI  - Haploperla choui sp. n. (Plecoptera: Chloroperlidae), a remarkable new stonefly
      from Qinling Mountains of China.
AB  - A new chloroperline stonefly species, Haploperla choui from the Qinling
      Mountains, Shaanxi Province, China is described. It is compared to other species
      of the genus known from Asia.

PMID- 26000436
TI  - Description of Loraxichthys lexa, new genus and species (Siluriformes:
      Loricariidae) from the Rio Huallaga Basin, central Peru, with notes on the
      morphology of the enigmatic Lipopterichthys carrioni Norman, 1935.
AB  - A new genus and species of armored catfish, Loraxichthys lexa, collected in 1955
      by the Catherwood Foundation Peruvian-Amazon Expedition from the vicinity of
      Tingo Maria, Huanuco, is described herein. Loraxichthys is diagnosed by two
      uniquely derived characters: two to four robust evertible posterior cheek
      odontodes with hooked tips, longer than odontodes anterior to them but no more
      than twice their length; and skin folds on dorsal border along first pelvic-fin
      ray crenulated in mature males. Loraxichthys lexa, new species, is only known
      from clear water tributaries of the Rio Huallaga in the vicinity of Tingo Maria.
      Additionally, notes on the morphology of the enigmatic species Lipopterichthys
      carrioni are included, and an artificial key for the genera Chaetostoma,
      Cordylancistrus, Dolichancistrus, Leptoancistrus, Lipopterichthys, and
      Loraxichthys is provided.

PMID- 26000437
TI  - Mexican Buprestidae: two new species of Acmaeodera Eschscholtz and a review of
      the genus Chalcophora Dejean.
AB  - Two distinctive new Mexican species of Acmaeodera Eschscholtz are described, A.
      xanthoskeles from the Yucatan Peninsula and A. inusitata from Michoacan. The
      Mexican species of the genus Chalcophora Dejean, C. hondurasica Casey and C.
      mexicana Waterhouse, are reviewed and discussed along with two U.S. and Canadian
      species, C. angulicollis (LeConte) and C. virginiensis (Drury). Chalcophora
      angulicollis is shown not to occur in Texas as has long been recorded.

PMID- 26000438
TI  - Ecological remarks and re-description of the hermit crab-associated pleustid
      amphipod Pleusymtes japonica (Gurjanova, 1938) (Crustacea: Amphipoda: Pleustidae:
      Pleusymtinae) from the Russian coasts of the Sea of Japan.
AB  - Numerous specimens of poorly known pleustid amphipod Pleusymtes japonica
      (Gurjanova, 1938) (Crustacea: Amphipoda: Pleustidae: Pleusymtinae) were found in
      association with large hermit crab Pagurus ochotensis Brandt, 1851 (Crustacea:
      Decapoda: Paguridae) near Furugelma Island in the Sea of Japan. This is the first
      report of the species in association with hermit crabs. Amphipods were found
      living close to the shell aperture and hermit crab feeding appendages. Color
      photographs, remarks on ecology and re-description of the species are given.

PMID- 26000439
TI  - When the Lophopids cross the Lydekker line from New Guinea, a new species for the
      genus Maana (Hemiptera: Fulgoromorpha).
AB  - A new species of the genus Maana Soulier-Perkins, 1998 is described, M. keiensis
      Soulier-Perkins et Stroinski, sp. nov. The presence of this species on the Kei
      Islands is discussed from its historical biogeography point of view.

PMID- 26000440
TI  - The adult stage of Paracloeodes charrua Emmerich & Nieto, 2009 (Ephemeroptera:
      Baetidae).

PMID- 26000441
TI  - Shear induced carboplatin binding within the cavity of a phospholipid mimic for
      increased anticancer efficacy.
AB  - Vesicles 107 +/- 19 nm in diameter, based on the self-assembly of tetra-para
      phosphonomethyl calix[4]- arene bearing n-hexyl moieties attached to the phenolic
      oxygen centres, are effective in binding carboplatin within the cavity of the
      macrocycle under shear induced within a dynamic thin film in a continuous flow
      vortex fluidic device. Post shearing the vesicles maintain similar diameters and
      retain carboplatin within the cavity of the calixarene in a hierarchical
      structure, with their size and morphology investigated using DLS, TEM, SEM and
      AFM. Location of the carboplatin was confirmed using NMR, FTIR, ESI-MS and EFTEM,
      with molecular modelling favouring the polar groups of carboplatin hydrogen
      bonded to phosphonic acid moieties and the four member cyclobutane ring directed
      into the cavity of the calixarene. The loading efficiency and release profile of
      carboplatin was investigated using LC-TOF/MS, with the high loading of the drug
      achieved under shear and preferential released at pH 5.5, offering scope for anti
      cancer drug delivery. The hierarchical structured vesicles increase the efficacy
      of carboplatin by 4.5 fold on ovarian cancer cells, lowered the IC50
      concentration by 10 fold, and markedly increased the percent of cells in the S
      phase (DNA replication) of the cell cycle.

PMID- 26000442
TI  - Blood pressure-lowering efficacy of loop diuretics for primary hypertension.
AB  - BACKGROUND: Antihypertensive drugs from the thiazide diuretic drug class have
      been shown to reduce mortality and cardiovascular morbidity. Loop diuretics are
      indicated and used to treat hypertension, but a systematic review of their blood
      pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular
      mortality or morbidity from randomized controlled trial (RCT) evidence has not
      been conducted. OBJECTIVES: To determine the dose-related decrease in systolic or
      diastolic blood pressure, or both, as well as adverse events leading to
      participant withdrawal and adverse biochemical effects (serum potassium, uric
      acid, creatinine, glucose and lipids profile) due to loop diuretics versus
      placebo control in the treatment of people with primary hypertension. SEARCH
      METHODS: We searched the Cochrane Hypertension Group Specialised Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 9), MEDLINE,
      MEDLINE In-Process, EMBASE, and ClinicalTrials.gov to 27 October 2014. SELECTION
      CRITERIA: We included double-blind randomized placebo-controlled trials of at
      least three weeks duration comparing loop diuretic with a placebo in people with
      primary hypertension defined as blood pressure greater than 140/90 mmHg at
      baseline. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      the risk of bias and extracted data. We used weighted mean difference and a fixed
      effects model to combine continuous outcome data. We analysed the drop outs due
      to adverse effects using relative risk ratio. MAIN RESULTS: Nine trials evaluated
      the dose-related blood pressure-lowering efficacy of five drugs within the loop
      diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg,
      piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and
      etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a
      mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood
      pressure-lowering efficacy of loop diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4
      (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical
      changes did not show a significant difference.We performed additional searches in
      2012 and 2014, which found no additional trials meeting the minimum inclusion
      criteria. AUTHORS' CONCLUSIONS: Based on the limited number of published RCTs,
      the systolic/diastolic blood pressure-lowering effect of loop diuretics is -8/-4
      mmHg, which is likely an overestimate. We graded the quality of evidence for both
      systolic and diastolic blood pressure estimates as "low" due to the high risk of
      bias of included studies and the high likelihood of publication bias. We found no
      clinically meaningful blood pressure-lowering differences between different drugs
      within the loop diuretic class. The dose-ranging effects of loop diuretics could
      not be evaluated. The review did not provide a good estimate of the incidence of
      harms associated with loop diuretics because of the short duration of the trials
      and the lack of reporting of adverse effects in many of the trials.

PMID- 26000443
TI  - Characterization of an Fe=N-NH2 Intermediate Relevant to Catalytic N2 Reduction
      to NH3.
AB  - The ability of certain transition metals to mediate the reduction of N2 to NH3
      has attracted broad interest in the biological and inorganic chemistry
      communities. Early transition metals such as Mo and W readily bind N2 and mediate
      its protonation at one or more N atoms to furnish M(N(x)H(y)) species that can be
      characterized and, in turn, extrude NH3. By contrast, the direct protonation of
      Fe-N2 species to Fe(N(x)H(y)) products that can be characterized has been
      elusive. Herein, we show that addition of acid at low temperature to
      [(TPB)Fe(N2)][Na(12-crown-4)] results in a new S = 1/2 Fe species. EPR, ENDOR,
      Mossbauer, and EXAFS analysis, coupled with a DFT study, unequivocally assign
      this new species as [(TPB)Fe=N-NH2](+), a doubly protonated hydrazido(2-) complex
      featuring an Fe-to-N triple bond. This unstable species offers strong evidence
      that the first steps in Fe-mediated nitrogen reduction by [(TPB)Fe(N2)][Na(12
      crown-4)] can proceed along a distal or "Chatt-type" pathway. A brief discussion
      of whether subsequent catalytic steps may involve early or late stage cleavage of
      the N-N bond, as would be found in limiting distal or alternating mechanisms,
      respectively, is also provided.

PMID- 26000444
TI  - Wind power error estimation in resource assessments.
AB  - Estimating the power output is one of the elements that determine the techno
      economic feasibility of a renewable project. At present, there is a need to
      develop reliable methods that achieve this goal, thereby contributing to wind
      power penetration. In this study, we propose a method for wind power error
      estimation based on the wind speed measurement error, probability density
      function, and wind turbine power curves. This method uses the actual wind speed
      data without prior statistical treatment based on 28 wind turbine power curves,
      which were fitted by Lagrange's method, to calculate the estimate wind power
      output and the corresponding error propagation. We found that wind speed
      percentage errors of 10% were propagated into the power output estimates, thereby
      yielding an error of 5%. The proposed error propagation complements the
      traditional power resource assessments. The wind power estimation error also
      allows us to estimate intervals for the power production leveled cost or the
      investment time return. The implementation of this method increases the
      reliability of techno-economic resource assessment studies. 

PMID- 26000445
TI  - Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self
      Renewal in Drosophila.
AB  - Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding
      genes, are often co-expressed with their host mRNAs. However, their functional
      interaction in development is largely unknown. Here we show that in Drosophila,
      miR-92a and miR-92b are embedded in the intron and 3'UTR of jigr1, respectively,
      and co-expressed with some jigr1 isoforms. miR-92a and miR-92b are highly
      expressed in neuroblasts of larval brain where Jigr1 expression is low. Genetic
      deletion of both miR-92a and miR-92b demonstrates an essential cell-autonomous
      role for these miRNAs in maintaining neuroblast self-renewal through inhibiting
      premature differentiation. We also show that miR-92a and miR-92b directly target
      jigr1 in vivo and that some phenotypes due to the absence of these miRNAs are
      partially rescued by reducing the level of jigr1. These results reveal a novel
      function of the miR-92 family in Drosophila neuroblasts and provide another
      example that local negative feedback regulation of host genes by intragenic
      miRNAs is essential for animal development. 

PMID- 26000446
TI  - Early versus Delayed Antiretroviral Therapy for HIV and Tuberculosis Co-Infected
      Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
AB  - OBJECTIVE: To compare important clinical outcomes between early and delayed
      initiation of antiretroviral therapy (ART) in adults who had a co-infection of
      human immunodeficiency virus (HIV) and tuberculosis (TB). METHODS: We performed a
      systematic search for relevant publications on PubMed, EMBASE, and the
      International Clinical Trials Registry Platform. We included randomized
      controlled trials (RCTs) that compared early ART initiation (within four weeks
      after anti-TB treatment starting) and delayed ART initiation (after eight weeks
      but less than twelve weeks of anti-TB treatment starting) in the course of TB
      treatment. Pooled estimates with corresponding 95% confidence interval (95%CI)
      were calculated with random-effects model. Sensitivity analysis was performed to
      investigate the stability of pooled estimates. RESULTS: A meta-analysis was
      evaluated from six RCTs with 2272 participants. Compared to delayed ART
      initiation, early ART initiation significantly reduces all-cause mortality in HIV
      positive patients with TB [incidence rate ratio (IRR) 0.75, 95%CI 0.59 to 0.95;
      I2 = 0.00%; p = 0.67], even though there is an increased risk for IRD [IRR 2.29,
      95%CI 1.81 to 2.91; I22 = 0.00%; p = 0.56]. Additionally, early ART initiation
      was not associated with an increased risk for grade 3-4 drug-related adverse
      events [IRR 0.99, 95%CI 0.83 to 1.18; I2 = 0.00%; p = 0.56]. CONCLUSIONS:
      Although limited evidence, our results provide support for early ART initiation
      in the course of anti-TB treatment. However, more well-designed cohort or
      intervention studies are required to further confirm our findings.

PMID- 26000447
TI  - DNA Barcoding Survey of Anurans across the Eastern Cordillera of Colombia and the
      Impact of the Andes on Cryptic Diversity.
AB  - Colombia hosts the second highest amphibian species diversity on Earth, yet its
      fauna remains poorly studied, especially using molecular genetic techniques. We
      present the results of the first wide-scale DNA barcoding survey of anurans of
      Colombia, focusing on a transect across the Eastern Cordillera. We surveyed 10
      sites between the Magdalena Valley to the west and the eastern foothills of the
      Eastern Cordillera, sequencing portions of the mitochondrial 16S ribosomal RNA
      and cytochrome oxidase subunit 1 (CO1) genes for 235 individuals from 52 nominal
      species. We applied two barcode algorithms, Automatic Barcode Gap Discovery and
      Refined Single Linkage Analysis, to estimate the number of clusters or
      "unconfirmed candidate species" supported by DNA barcode data. Our survey
      included ~7% of the anuran species known from Colombia. While barcoding
      algorithms differed slightly in the number of clusters identified, between three
      and ten nominal species may be obscuring candidate species (in some cases, more
      than one cryptic species per nominal species). Our data suggest that the high
      elevations of the Eastern Cordillera and the low elevations of the Chicamocha
      canyon acted as geographic barriers in at least seven nominal species, promoting
      strong genetic divergences between populations associated with the Eastern
      Cordillera. 

PMID- 26000448
TI  - Noteworthy Facts about a Methane-Producing Microbial Community Processing Acidic
      Effluent from Sugar Beet Molasses Fermentation.
AB  - Anaerobic digestion is a complex process involving hydrolysis, acidogenesis,
      acetogenesis and methanogenesis. The separation of the hydrogen-yielding (dark
      fermentation) and methane-yielding steps under controlled conditions permits the
      production of hydrogen and methane from biomass. The characterization of
      microbial communities developed in bioreactors is crucial for the understanding
      and optimization of fermentation processes. Previously we developed an effective
      system for hydrogen production based on long-term continuous microbial cultures
      grown on sugar beet molasses. Here, the acidic effluent from molasses
      fermentation was used as the substrate for methanogenesis in an upflow anaerobic
      sludge blanket bioreactor. This study focused on the molecular analysis of the
      methane-yielding community processing the non-gaseous products of molasses
      fermentation. The substrate for methanogenesis produces conditions that favor the
      hydrogenotrophic pathway of methane synthesis. Methane production results from
      syntrophic metabolism whose key process is hydrogen transfer between bacteria and
      methanogenic Archaea. High-throughput 454 pyrosequencing of total DNA isolated
      from the methanogenic microbial community and bioinformatic sequence analysis
      revealed that the domain Bacteria was dominated by Firmicutes (mainly
      Clostridia), Bacteroidetes, delta- and gamma-Proteobacteria, Cloacimonetes and
      Spirochaetes. In the domain Archaea, the order Methanomicrobiales was
      predominant, with Methanoculleus as the most abundant genus. The second and third
      most abundant members of the Archaeal community were representatives of the
      Methanomassiliicoccales and the Methanosarcinales. Analysis of the methanogenic
      sludge by scanning electron microscopy with Energy Dispersive X-ray Spectroscopy
      and X-ray diffraction showed that it was composed of small highly heterogeneous
      mineral-rich granules. Mineral components of methanogenic granules probably
      modulate syntrophic metabolism and methanogenic pathways. A rough functional
      analysis from shotgun data of the metagenome demonstrated that our knowledge of
      methanogenesis is poor and/or the enzymes responsible for methane production are
      highly effective, since despite reasonably good sequencing coverage, the details
      of the functional potential of the microbial community appeared to be incomplete.

PMID- 26000449
TI  - The hydrophobic temperature dependence of amino acids directly calculated from
      protein structures.
AB  - The hydrophobic effect is the main driving force in protein folding. One can
      estimate the relative strength of this hydrophobic effect for each amino acid by
      mining a large set of experimentally determined protein structures. However, the
      hydrophobic force is known to be strongly temperature dependent. This temperature
      dependence is thought to explain the denaturation of proteins at low
      temperatures. Here we investigate if it is possible to extract this temperature
      dependence directly from a large set of protein structures determined at
      different temperatures. Using NMR structures filtered for sequence identity, we
      were able to extract hydrophobicity propensities for all amino acids at five
      different temperature ranges (spanning 265-340 K). These propensities show that
      the hydrophobicity becomes weaker at lower temperatures, in line with current
      theory. Alternatively, one can conclude that the temperature dependence of the
      hydrophobic effect has a measurable influence on protein structures. Moreover,
      this work provides a method for probing the individual temperature dependence of
      the different amino acid types, which is difficult to obtain by direct
      experiment. 

PMID- 26000450
TI  - Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the
      Type VI Secretion System.
AB  - Two-component signal transduction systems (TCS) are used by bacteria to sense and
      respond to their environment. TCS are typically composed of a sensor histidine
      kinase (HK) and a response regulator (RR). The Vibrio cholerae genome encodes 52
      RR, but the role of these RRs in V. cholerae pathogenesis is largely unknown. To
      identify RRs that control V. cholerae colonization, in-frame deletions of each RR
      were generated and the resulting mutants analyzed using an infant mouse intestine
      colonization assay. We found that 12 of the 52 RR were involved in intestinal
      colonization. Mutants lacking one previously uncharacterized RR, VCA0566 (renamed
      VxrB), displayed a significant colonization defect. Further experiments showed
      that VxrB phosphorylation state on the predicted conserved aspartate contributes
      to intestine colonization. The VxrB regulon was determined using whole genome
      expression analysis. It consists of several genes, including those genes that
      create the type VI secretion system (T6SS). We determined that VxrB is required
      for T6SS expression using several in vitro assays and bacterial killing assays,
      and furthermore that the T6SS is required for intestinal colonization. vxrB is
      encoded in a four gene operon and the other vxr operon members also modulate
      intestinal colonization. Lastly, though DeltavxrB exhibited a defect in single
      strain intestinal colonization, the DeltavxrB strain did not show any in vitro
      growth defect. Overall, our work revealed that a small set of RRs is required for
      intestinal colonization and one of these regulators, VxrB affects colonization at
      least in part through its regulation of T6SS genes. 

PMID- 26000451
TI  - Motor Inhibition during Overt and Covert Actions: An Electrical Neuroimaging
      Study.
AB  - Given ample evidence for shared cortical structures involved in encoding actions,
      whether or not subsequently executed, a still unsolved problem is the
      identification of neural mechanisms of motor inhibition, preventing "covert
      actions" as motor imagery from being performed, in spite of the activation of the
      motor system. The principal aims of the present study were the evaluation of: 1)
      the presence in covert actions as motor imagery of putative motor inhibitory
      mechanisms; 2) their underlying cerebral sources; 3) their differences or
      similarities with respect to cerebral networks underpinning the inhibition of
      overt actions during a Go/NoGo task. For these purposes, we performed a high
      density EEG study evaluating the cerebral microstates and their related sources
      elicited during two types of Go/NoGo tasks, requiring the execution or
      withholding of an overt or a covert imagined action, respectively. Our results
      show for the first time the engagement during motor imagery of key nodes of a
      putative inhibitory network (including pre-supplementary motor area and right
      inferior frontal gyrus) partially overlapping with those activated for the
      inhibition of an overt action during the overt NoGo condition. At the same time,
      different patterns of temporal recruitment in these shared neural inhibitory
      substrates are shown, in accord with the intended overt or covert modality of
      action performance. The evidence that apparently divergent mechanisms such as
      controlled inhibition of overt actions and contingent automatic inhibition of
      covert actions do indeed share partially overlapping neural substrates, further
      challenges the rigid dichotomy between conscious, explicit, flexible and
      unconscious, implicit, inflexible forms of motor behavioral control. 

PMID- 26000452
TI  - Pathways of Amino Acid Degradation in Nilaparvata lugens (Stal) with Special
      Reference to Lysine-Ketoglutarate Reductase/Saccharopine Dehydrogenase (LKR/SDH).
AB  - Nilaparvata lugens harbors yeast-like symbionts (YLSs). In present paper, a
      genome-wide analysis found 115 genes from Ni. lugens and 90 genes from YLSs that
      were involved in the metabolic degradation of 20 proteinogenic amino acids. These
      205 genes encoded for 77 enzymes. Accordingly, the degradation pathways for the
      20 amino acids were manually constructed. It is postulated that Ni. lugens can
      independently degrade fourteen amino acids (threonine, alanine, glycine, serine,
      aspartate, asparagine, phenylalanine, tyrosine, glutamate, glutamine, proline,
      histidine, leucine and lysine). Ni. lugens and YLSs enzymes may work
      collaboratively to break down tryptophan, cysteine, arginine, isoleucine,
      methionine and valine. We cloned a lysine-ketoglutarate reductase/saccharopine
      dehydrogenase gene (Nllkr/sdh) that encoded a bifunctional enzyme catalyzing the
      first two steps of lysine catabolism. Nllkr/sdh is widely expressed in the first
      through fifth instar nymphs and adults, and is highly expressed in the fat body,
      ovary and gut in adults. Ingestion of dsNllkr/sdh by nymphs successfully knocked
      down the target gene, and caused nymphal/adult mortality, shortened nymphal
      development stage and reduced adult fresh weight. Moreover, Nllkr/sdh knockdown
      resulted in three defects: wings were shortened and thickened; cuticles were
      stretched and thinned; and old nymphal cuticles remained on the tips of legs and
      abdomen and were not completely shed. These data indicate that impaired lysine
      degradation negatively affects the survival and development of Ni. lugens. 

PMID- 26000455
TI  - Meta-analysis of the IL23R and IL12B polymorphisms in multiple sclerosis.
AB  - PURPOSE: Polymorphisms in the genes encoding interleukin-23 receptor (IL23R) and
      the p40 subunit of IL-12/23 (IL12B) have been implicated in multiple sclerosis
      (MS) risk. However, results of different studies are inconsistent. Our aim was to
      perform a meta-analysis on this topic. METHODS: We assessed two variants
      (rs10889677 and rs7517847) of IL23R and the A1188C polymorphism (rs3212227) of
      IL12B. Electronic databases (PubMed, Web of Science and Scopus) were searched for
      eligible studies published until September 2014. Odds ratio (OR) and 95%
      confidence interval (95% CI) were used to investigate the strength of association
      in dominant, recessive, homozygote and allelic comparison models. RESULTS: Seven
      case-control studies with 2250 MS patients and 2320 controls were included in
      this meta-analysis. The pooled results showed no association of rs10889677 and
      rs7517847 with MS risk in any of the genetic models. Although the pooled analysis
      showed an association between rs3212227 and MS in all study subjects in dominant
      (OR = 0.81, 95% CI: 0.66-0.99, P(h) = 0.480, P(z) = 0.044) and allelic comparison
      (OR = 0.84, 95% CI: 0.72-0.98, P(h) = 0.967, P(z) = 0.030) models, subgroup
      analysis based on ethnicity did not suggest an association between rs3212227 and
      MS risk in Caucasians in any of the genetic models, and there was no association
      between rs3212227 and MS risk in an Asian group. CONCLUSIONS: The IL23R
      polymorphisms rs10889677, rs7517847, and the IL12B polymorphism rs3212227 are not
      associated with MS risk.

PMID- 26000453
TI  - Diversity of Intestinal Clostridium coccoides Group in the Japanese Population,
      as Demonstrated by Reverse Transcription-Quantitative PCR.
AB  - We used sensitive rRNA-targeted reverse transcription-quantitative PCR (RT-qPCR)
      to quantify the Clostridium coccoides group, which is a major anaerobic
      population in the human intestine. For this purpose, the C. coccoides group was
      classified into 3 subgroups and 19 species for expediency in accordance with the
      existing database, and specific primers were newly developed to evaluate them.
      Population levels of the C. coccoides group in human feces determined by RT-qPCR
      were equivalent to those determined by fluorescence in situ hybridization. RT
      qPCR analysis of fecal samples from 96 volunteers (32 young children, 32 adults
      and 32 elderly) by using the 22 new primer sets together with the C. coccoides
      group-specific primer setm revealed that (i) total counts obtained as the sum of
      the 3 subgroups and 19 species were equivalent to the results obtained by using
      the C. coccoides group-specific primer set; (ii) total C. coccoides-group counts
      in the elderly were significantly lower than those in young children and adults;
      (iii) genus Blautia was the most common subgroup in the human intestinal C.
      coccoides-group populations at all age populations tested; (iv) the prevalences
      of Fusicatenibacter saccharivorans and genus Dorea were significantly higher in
      adults than in young children and the elderly; and (v) the prevalences of C.
      scindens and C. hylemonae, both of which produce secondary bile acid in the human
      intestine, were significantly higher in the elderly than in young children and
      adults. Hierarchical clustering and principal component analysis showed clear
      separation of the bacterial components between adult and elderly populations.
      Taken together, these data suggest that aging plays an important role in the
      diversity of C. coccoides-group populations in human intestinal microbiota;
      changes in this diversity likely influence the health of the host. 

PMID- 26000456
TI  - Correction to Surface Area and the Seabed Area, Volume, Depth, Slope, and
      Topographic Variation for the World's Seas, Oceans, and Countries.

PMID- 26000454
TI  - Urbanization of scrub typhus disease in South Korea.
AB  - BACKGROUND: Scrub typhus is an endemic disease in Asia. It has been a rural
      disease, but indigenous urban cases have been observed in Seoul, South Korea.
      Urban scrub typhus may have a significant impact because of the large population.
      METHODS: Indigenous urban scrub typhus was epidemiologically identified in Seoul,
      the largest metropolitan city in South Korea, using national notifiable disease
      data from 2010 to 2013. For detailed analysis of clinical features, patients from
      one hospital that reported the majority of cases were selected and compared to a
      historic control group. Chigger mites were prospectively collected in the city
      using a direct chigger mite-collecting trap, and identified using both phenotypic
      and 18S rDNA sequencing analyses. Their infection with Orientia tsutsugamushi was
      confirmed by sequencing the 56-kDa antigen gene. RESULTS: Eighty-eight cases of
      urban scrub typhus were determined in Seoul. The possible sites of infection were
      mountainous areas (56.8%), city parks (20.5%), the vicinity of one's own
      residence (17.0%), and riversides (5.7%). Eighty-seven chigger mites were
      collected in Gwanak mountain, one of the suspected infection sites in southern
      Seoul, and seventy-six (87.4%) of them were identified as Helenicula miyagawai
      and eight (9.2%) as Leptotrombidium scutellare. Pooled DNA extracted from H.
      miyagawai mites yielded O. tsutsugamushi Boryong strain. Twenty-six patients from
      one hospital showed low APACHE II score (3.4 +/- 2.7), low complication rate
      (3.8%), and no hypokalemia. CONCLUSIONS: We identified the presence of indigenous
      urban scrub typhus in Seoul, and a subgroup of them had mild clinical features.
      The chigger mite H. miyagawai infected with O. tsutsugamushi within the city was
      found. In endemic area, urban scrub typhus needs to be considered as one of the
      differential febrile diseases and a target for prevention.

PMID- 26000457
TI  - Carbon-Anchored MnO Nanosheets as an Anode for High-Rate and Long-Life Lithium
      Ion Batteries.
AB  - Developing electrode materials with high rate as well as prolonged cycle is
      particularly necessary for the ever-growing market penetration of electric
      vehicles and hybrid electric vehicle. Herein, we demonstrate a facile and
      efficient strategy to synthesize MnO/C hybrid via freeze-drying followed by
      thermal treatment in N2 atmosphere. The MnO nanosheets are firmly anchored onto
      carbon layers to form MnO/C hybrid. When used as an anode in lithium-ion
      batteries, the typical MnO/C hybrid displays a high initial Coulombic efficiency
      of 83.1% and delivers a high capacity of 1449.8 mAh g(-1) after 100 cycles at 0.3
      A g(-1). Furthermore, the typical MnO/C hybrid can still maintain significantly
      high capacity of 1467.0 mAh g(-1) after 2000 cycles at 5 A g(-1), which may be
      the best performance reported so far for MnO-based materials. The superior
      electrochemical performance of the MnO/C hybrid may be attributed to its unique
      microstructure features such as effective conductive pathway of carbon sheets,
      firm connection between MnO and carbon sheets, and small-sized MnO. 

PMID- 26000458
TI  - Role of Counterions in Controlling the Properties of Ultrasonically Generated
      Chitosan-Stabilized Oil-in-Water Emulsions.
AB  - An oil-in-water emulsion was ultrasonically prepared in aqueous chitosan
      solutions containing different counterions. Tetradecane was used as the oil phase
      in order to mimic nonpolar substances used in food processes. Various acids were
      used to dissolve chitosan, and we found that conjugate bases of the acids used,
      which act as counterions to neutralize the positive charges of ammonium ions
      present in the chitosan backbone, played a significant role in controlling the
      size, size distribution, and stability of chitosan-encapsulated tedradecane
      emulsion droplets (microspheres). The counterion effect is also found to be
      strongly dependent upon tetradecane (TD)/chitosan (CS) ratio and ultrasonic
      power. Key observations are: (i) for a given TD/CS ratio, the size and size
      distribution decrease when the acid is varied from nitric acid to benzenesulfonic
      acid at high TD/CS ratio, and the effect becomes less significant at low TD/CS
      ratio; (ii) for a given acid, the size and size distribution increase with an
      increase in TD/CS ratio; and (iii) at low TD/CS ratio the size and size
      distribution are significantly influenced by the viscosity of the system. A
      possible mechanism for the observed counterion effect is proposed. The role of
      counterions, solution viscosity, and ultrasonic power in controlling the physical
      and functional properties of ultrasonically generated chitosan-stabilized
      tetradecane microspheres is discussed in detail. The key new finding of this
      study is that it is possible to form stable emulsions without the addition of
      external emulsifiers and stabilizers, but only using chitosan with different
      acids to dissolve chitosan. This strategy could be used in the generation of
      stable food emulsions.